PMID- 12208769
TI  - The smooth muscle relaxant effect of hydrogen sulphide in vitro: evidence for a
      physiological role to control intestinal contractility.
AB  - 1. Sodium hydrogen sulphide (NaHS), a donor of hydrogen sulphide (H(2)S),
      produced dose-related relaxation of the rabbit isolated ileum (EC(50), 76.4+/-7.9
      microM) and rat vas deferens (EC(50), 64.8+/-5.4 microM) and reduced ACh-mediated
      contraction of the guinea-pig isolated ileum. 2. NaHS also reduced the response
      of the guinea-pig (EC(50), 80.0+/-5.7 microM) and rat (EC(50), 108.2+/-11.2
      microM) ileum preparations to electrical stimulation of the intramural nerves. In
      guinea-pig ileum this effect was spontaneously reversible and mimicked by sodium
      nitroprusside (SNP, EC(50), 2.1 microM). Combination of NaHS (20 microM) with SNP
      (0.5 microM) produced a greater than additive inhibition of the twitch response
      of the ileum to electrical stimulation. 3. The inhibitory effect of NaHS on the
      field-stimulated guinea-pig ileum was unaffected by pretreatment with L-NAME (100
      microM), indomethacin (10 microM), naloxone (1 microM) or glibenclamide (100
      microM). Furthermore, NaHS (200 microM) did not affect the contractile response
      of the ileum to KCl (10 to 60 mM). 4. Propargylglycine (PAG, 1 mM) and beta
      cyanoalanine (BCA, 1 mM) (inhibitors of cystathionine-gamma-lyase) but not
      aminooxyacetic acid (AOAA, 1 mM) (inhibitor of cystathionine-beta-synthetase)
      caused a slowly developing increase in the contraction of the guinea-pig ileum to
      field stimulation. This effect was reversed by cysteine (1 mM). 5. These results
      show that NaHS relaxes gastrointestinal and urogenital smooth muscle and suggest
      that H(2)S is responsible for these effects. The possibility that endogenous
      H(2)S, formed as a consequence of activation of intramural nerves, plays a part
      in controlling the contractility of the guinea-pig ileum is discussed.

PMID- 12208770
TI  - Accumulation of platelets in the lung and liver and their degranulation following
      antigen-challenge in sensitized mice.
AB  - 1. Mast cells and basophils are believed to trigger allergic reactions and
      anaphylaxis. They rapidly release histamine (H), a typical mediator of
      inflammation, in response to antigens. In the mouse, platelets contain much 5
      hydroxytryptamine (5HT), an additional inflammatory mediator, while human
      platelets contain both H and 5HT. Here, we examined the response of platelets in
      sensitized mice to antigen challenge. 2. Platelets accumulated in the lung and
      liver almost immediately after intravenous injection of ovalbumin (OVA), in mice
      sensitized to it, and platelet degranulation occurred during these reactions. 3.
      These responses of platelets preceded H release from mast cells and/or basophils,
      occurred at doses of OVA lower than those inducing H release, and contributed to
      the signs of shock. 4. We reported previously that intravenous injection into
      mice of LPS (a membrane constituent of gram-negative bacteria) induces a similar
      platelet response (accumulation of platelets in the lung and liver) and shock. 5.
      Blood that has passed through the body (other than the digestive tract) passes
      first to the lungs before being recirculated by the heart, and blood that has
      passed through the digestive tract passes next to the liver. Thus, our findings
      suggest that in addition to their role in haemostasis, platelets, tiny anuclear
      cytoplasts, may be important in both innate and acquired immunity, and that the
      lung and liver may be the fronts at which platelets wage war on pathogens.

PMID- 12208771
TI  - Beta 3-adrenoceptor in rat aorta: molecular and biochemical characterization and
      signalling pathway.
AB  - 1. We have previously demonstrated that beta(3)-adrenoceptor (beta(3)-AR)
      stimulation induces endothelium-dependent vasorelaxation in rat aorta through the
      activation of an endothelial NO synthase associated with an increase in
      intracellular cGMP. The aim of the present study was to localise beta(3)-AR to
      confirm our functional study and to complete the signalling pathway of beta(3)-AR
      in rat aorta. 2. By RT-PCR, we have detected beta(3)-AR transcripts both in aorta
      and in freshly isolated endothelial cells. The absence of markers for adipsin or
      hormone-sensitive lipase in endothelial cells excluded the presence of beta(3)-AR
      from adipocytes. The localization of beta(3)-AR in aortic endothelial cells was
      confirmed by immunohistochemistry using a rat beta(3)-AR antibody. 3. To identify
      the G protein linked to beta(3)-AR, experiments were performed in rat pre-treated
      with PTX (10 microg kg(-1)), a G(i/0) protein inhibitor. The blockage of G(i/0)
      protein by PTX was confirmed by the reduction of vasorelaxation induced by UK
      14304, a selective alpha(2)-AR agonist. The cumulative concentration-response
      curve for SR 58611A, a beta(3)-AR agonist, was not significantly modified on
      aorta rings from PTX pre-treated rats. 4. At the same level of contraction, the
      relaxations induced by 10 microM SR 58611A were significantly reduced in 30 mM
      KCl pre-constricted rings (E(max)=16.7+/-8.4%, n=5), in comparison to
      phenylephrine (0.3 microM) pre-constricted rings (E(max)=49.11+/-11.0%, n=5,
      P<0.05). In addition, iberotoxin (0.1 microM), glibenclamide (1 microM) and 4
      aminopyridine (1 mM), selective potassium channels blockers of K(Ca), K(ATP), and
      K(v) respectively, decreased the SR 58611A-mediated relaxation. 5. We conclude
      that beta(3)-AR is preferentially expressed in rat aortic endothelial cells.
      Beta(3)-AR-mediated aortic relaxation is independent of G(i/0) proteins
      stimulation, but results from the activation of several potassium channels,
      K(Ca), K(ATP), and K(v).

PMID- 12208772
TI  - Effects of mutations of a glutamine residue in loop D of the alpha7 nicotinic
      acetylcholine receptor on agonist profiles for neonicotinoid insecticides and
      related ligands.
AB  - 1. Neonicotinoid insecticides are agonists of insect nicotinic acetylcholine
      receptors (AChRs) and show selective toxicity for insects over vertebrates. To
      elucidate the molecular basis of the selectivity, amino acid residues influencing
      neonicotinoid sensitivity were investigated by site-directed mutagenesis of the
      chicken alpha7 nicotinic AChR subunit, based on the crystal structure of an ACh
      binding protein (AChBP). 2. In the ligand binding site of AChBP, Q55 in loop D is
      close to Y164 in loop F that corresponds to G189 of the alpha7 nicotinic
      receptor. Since Q55 of AChBP is preserved as Q79 in the alpha7 nicotinic receptor
      and the G189D and G189E mutations have been found to reduce the neonicotinoid
      sensitivity, we investigated effects of Q79E, Q79K and Q79R mutations on the
      neonicotinoid sensitivity of the alpha7 receptor expressed in Xenopus laevis
      oocytes to evaluate contributions of the glutamine residue to nicotinic AChR
      neonicotinoid interactions. 3. The Q79E mutation markedly reduced neonicotinoid
      sensitivity of the alpha7 nicotinic AChR whereas the Q79K and Q79R mutations
      increased sensitivity, suggesting electronic interactions of the neonicotinoids
      with the added residues. 4. By contrast, the Q79E mutation scarcely influenced
      responses of the alpha7 nicotinic receptor to ACh, (-)-nicotine and desnitro
      imidacloprid (DN-IMI), an imidacloprid derivative lacking the nitro group,
      whereas the Q79K and Q79R mutations reduced the sensitivity to these ligands. The
      results indicate that the glutamine residue of the alpha7 nicotinic receptor is
      likely to be located close to the nitro group of the insecticides in the
      nicotinic receptor-insecticide complex.

PMID- 12208773
TI  - Analgesic effect of intrathecally administered orexin-A in the rat formalin test
      and in the rat hot plate test.
AB  - 1. Orexin-A and orexin-B (also known as hypocretin-1 and hypocretin-2) are
      hypothalamic peptides and regulate feeding behaviour, energy metabolism and the
      sleep-wake cycle. Orexin-A binds equally to both orexin-1 and orexin-2 receptors,
      while orexin-B has a preferential affinity for orexin-2 receptors. 2. Orexins are
      also known to be concentrated in superficial laminae of the spinal dorsal horn,
      and orexin-A and orexin-1 receptors are found in the dorsal root ganglion cells.
      3. In the present study, the authors examined the effect of intrathecal injection
      of either orexin-A or orexin-B in the rat formalin test (a model of inflammatory
      pain) and in the rat hot plate test. The paw formalin injection induces biphasic
      flinching (phase 1: 0-6 min; phase 2: 10-60 min) of the injected paw. 4.
      Intrathecal injection of orexin-A, but not orexin-B, decreased the sum of
      flinches in phases 1 and 2 in the formalin test and increased the hot plate
      latency. These effects of orexin-A were completely antagonized by pre-treatment
      with SB-334867, a selective orexin-1 receptor antagonist. Intrathecal injection
      of SB-334867 alone had no effect in the formalin test or in the hot plate test.
      5. Intrathecal injection of orexin-A suppressed the expression of Fos-like
      immunoreactivity (Fos-LI), induced by paw formalin injection, in laminae I-II of
      L4-5 of the spinal cord. 6. These data suggest that the spinal orexin-1 receptor
      is involved in the nociceptive transmission and that the activation of the spinal
      orexin-1 receptor produces analgesic effects in the rat formalin test and in the
      rat hot plate test.

PMID- 12208774
TI  - ADP-sensitive purinoceptors induce steroidogenesis via adenylyl cyclase
      activation in bovine adrenocortical fasciculata cells.
AB  - 1. The role of P2Y receptors in the production of cAMP and the activation of
      protein kinase A (PKA) was studied with respect to the regulation of the
      steroidogenesis in primary cultures of bovine adrenocortical fasciculata cells
      (BAFCs). 2. ADP and ATP stimulated cAMP production with EC(50) values of 23.7+/
      6.8 microM and 40.1+/-5.5 microM, respectively. In contrast, the EC(50) of BzATP
      for cAMP production was 153.0+/-37.4 microM. Adenosine and AMP (0.1-1000 microM)
      were much less effective than ADP and ATP. 2MeSADP and UTP did not exert
      detectable effects. ADP (10 and 100 microM) significantly stimulated
      steroidogenesis; the process was blocked by an adenylyl cyclase inhibitor SQ22536
      (100 microM) but not by the P2Y(1) receptor antagonist MRS2179 (100 microM). 3.
      Real-time imaging of the PKA activity with the dye ARII, which became less
      fluorescent upon phosphorylation, revealed that ADP (100 microM) immediately
      activated PKA. These effects could be mimicked by forskolin (100 microM) and were
      blocked by the PKA inhibitor H89 (50 microM). UTP (100 microM) did not activate
      PKA. 4. The cytoplasm harvested from morphologically and electrophysiologically
      identified single BAFCs contained mRNA for P2Y(2) but not for P2Y(1), P2Y(4),
      P2Y(11) or P2Y(12) receptors, as confirmed by single-cell RT-PCR amplification
      (50 cycles). 5. These results suggest an expression of an ADP-sensitive G(s)
      coupled purinoceptor in BAFCs. We propose that this not yet described type of P2Y
      receptor might mediate the extracellular purine-activated steroidogenesis via
      cAMP/PKA-mediated pathways, independently from the pathways involving InsP(3)
      production and consequent intracellular Ca(2+) increase.

PMID- 12208775
TI  - Induction of insulin resistance by high-sucrose feeding does not raise mean
      arterial blood pressure but impairs haemodynamic responses to insulin in rats.
AB  - 1. This study was undertaken to further investigate the effects of a sucrose
      enriched diet on vascular function and insulin sensitivity in rats. 2. Male
      Sprague-Dawley rats were randomized to receive a sucrose- or regular rat chow
      diet for 4 weeks. A first group of sucrose- and chow-fed rats was instrumented
      with pulsed Doppler flow probes and intravascular catheters to determine blood
      pressure, heart rate, regional blood flows and insulin sensitivity in conscious
      rats. Insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp
      technique. Glucose transport activity was examined in isolated muscles by using
      the glucose analogue [(3)H]-2-deoxy-D-glucose. A second group of sucrose- and
      chow-fed rats was used to obtain information regarding nitric oxide synthase
      (NOS) isozymes protein expression in muscles, and determine endothelin content in
      vascular tissues isolated from both dietary groups. 3. Sucrose feeding was found
      to induce insulin resistance, but had no effect on resting blood pressure, heart
      rate, or regional haemodynamics. This insulin resistance was accompanied by
      alteration in the vascular responses to insulin. Insulin-mediated skeletal muscle
      vasodilation was impaired, whereas the mesenteric vasoconstrictor response was
      potentiated in sucrose-fed rats. A reduction in eNOS protein content in muscle
      and an increase in vascular endothelin peptide were noted in these animals.
      Moreover, a reduction in insulin-simulated glucose transport activity was also
      noted in muscles isolated from sucrose-fed rats. 4. Together these data suggest
      that a cluster of metabolic and haemodynamic abnormalities occur in response to
      the intake of simple sugars in rats.

PMID- 12208776
TI  - Production of inflammatory mediators by renal epithelial cells is insensitive to
      glucocorticoids.
AB  - 1. In the present study we investigated the effect of glucocorticoids on the
      activation of renal tubular epithelial cells, which are thought to play an
      important role in inflammatory processes in the kidney. 2. Activation of renal
      epithelial cells by IL-1, TNF-alpha or CD40L resulted in increased production of
      cytokines and chemokines. Both in the renal epithelial cell line HK-2 and in
      primary cultures of human proximal tubular epithelial cells (PTEC) production of
      IL-6, IL-8 and monocyte chemotactic protein 1 (MCP-1) was not inhibited by
      glucocorticoids, independent of the stimulus. 3. In contrast, dexamethasone
      strongly inhibited cytokine production by immortalized renal fibroblasts and an
      airway epithelial cell line (A549). 4. Stimulation of renal epithelial cells
      resulted in activation of NF-kappaB, a pivotal transcription factor in the
      regulation of cytokine genes, as was shown by IkappaB-alpha degradation and
      increased DNA-binding activity. In contrast to dexamethasone, addition of the NF
      kappaB inhibitors pyrrolidine dithiocarbamate (PDTC) and n-tosyl-l-phenylalanine
      chloromethyl ketone (TPCK) completely abolished cytokine and chemokine
      production. 5. Renal epithelial cells express abundant levels of the functional
      glucocorticoid receptor alpha (GRalpha) isoform and low levels of the inhibitory
      beta isoform (GRbeta). 6. In conclusion, cytokine production by renal epithelial
      cells is insensitive to the inhibitory effects of glucocorticoids. The lack of
      dexamethasone-mediated inhibition was specific for renal epithelial cells and
      could not be explained by an increased expression of the glucocorticoid receptor
      beta isoform.

PMID- 12208777
TI  - Role of Rho kinase signalling in healthy and varicose human saphenous veins.
AB  - 1. The present study was performed to determine the role of Rho-Rho kinase
      signalling pathway in smooth muscle cells from both healthy and varicose human
      saphenous vein. 2. The Rho kinase inhibitor Y-27632 inhibited the noradrenaline
      (NA)-induced contraction in human saphenous veins with IC(50) corresponding to
      0.5 microM and 10.9 microM in control and varicose veins, respectively. The
      maximal amplitude of the NA-induced contraction was smaller in varicose vein
      compared to control (1263+/-172 mg versus 1974+/-245 mg, P<0.05). 3. In beta
      escin permeabilized strips, GTPgammaS induced a rise in tension that was
      inhibited by Y-27632. The amplitude of the GTPgammaS-induced contraction was
      smaller in varicose compared to control veins (23.1+/-2.4% versus 41.3+/-2.2%,
      P<0.002). 4. In smooth muscle cells, Y-27632 induced disassembly of both actin
      cytoskeleton and extracellular fibronectin matrix. In comparison to control
      cells, varicose vein smooth muscle cells show decreased actin cytoskeleton
      organization and reduction of fibronectin matrix deposition. 5. The Rho proteins
      Rnd1 and RhoA, and Rho kinase 1 are expressed in human saphenous veins. A 2.6
      fold reduction of Rho kinase expression was found in varicose veins. 6. These
      results indicate that RhoA-Rho kinase mediated Ca(2+) sensitization of the
      contraction and regulated actin cytoskeleton and extracellular fibronectin matrix
      assembly in human saphenous smooth muscle. The decrease of Rho kinase expression
      and Rho kinase-dependent functions detected in smooth muscle from varicose veins
      supports a role of this signalling pathway in the functional alterations of the
      vein wall occurring in the course of the disease.

PMID- 12208778
TI  - Different mechanism of LPS-induced vasodilation in resistance and conductance
      arteries from SHR and normotensive rats.
AB  - 1. The direct and endothelium-dependent effects of lipopolysaccharide (LPS) were
      investigated on resistance and conductance arteries from normotensive Wistar
      (NWR) and spontaneously hypertensive (SHR) rats. 2. In both NWR and SHR, LPS
      induced dose-dependent relaxations of the mesenteric vascular bed, which were
      inhibited by L-NNA in SHR but not in NWR. Iberiotoxin (IBTX) inhibited the
      responses to LPS in both groups, indicating the participation of high conductance
      Ca(2+)-dependent K(+) channels. 3. In mesenteric artery rings, the resting
      membrane potentials and the hyperpolarizing responses of NWR to LPS did not
      differ in endothelized and denuded preparations but L-NNA inhibited the responses
      only in endothelized rings. These responses were reduced by bosentan, suggesting
      that endothelin release may mask a possible hyperpolarizing response to LPS. The
      hyperpolarizing responses to LPS were blocked by IBTX in both endothelized and de
      endothelized NWR rings. In the SHR only intact rings showed hyperpolarization to
      LPS, which was inhibited by IBTX and byL-NNA. 4. In SHR aortic endothelized or
      denuded rings, LPS induced hyperpolarizing responses which, in endothelized
      rings, were partially blocked by L-NNA, by IBTX or by glibenclamide, but totally
      abolished by IBTX plus glibenclamide. No response to LPS was observed in NWR
      aortic rings. 5. Our results indicate that LPS activates large conductance Ca(2+)
      sensitive K(+) channels located in the smooth muscle cell membrane both directly
      and indirectly, through NO release from the endothelium in NWR, whereas NO is the
      major mediator of the LPS responses in SHR resistance vessels.

PMID- 12208779
TI  - Bertosamil blocks HERG potassium channels in their open and inactivated states.
AB  - 1. Bertosamil is chemically related to the class-III anti-arrhythmic drug
      tedisamil and has been developed as a bradycardic, anti-ischemic and anti
      arrhythmic drug. Its anti-arrhythmic properties might in part be attributed to
      its block of voltage-dependent potassium channels Kv(1.2), Kv(1.4). and Kv(1.5).
      However, HERG-potassium channel block as an important target for class-III drugs
      has not yet been investigated. 2. We investigated the effect of bertosamil on the
      HERG potassium channel heterologously expressed in Xenopus oocytes with the two
      electrode voltage-clamp technique. 3. Bertosamil (70 microM) inhibited HERG tail
      currrent after a test pulse to 30 mV by 49.3+/-8.4% (n=5) and the IC(50) was 62.7
      microM. Onset of block was fast, i.e. 90% of inhibition developed within 180+/
      8.22 s (n=5), and block was totally reversible upon washout within 294+/-38.7 s
      (n=5). 4. Bertosamil-induced block of HERG potassium channels was state-dependent
      with block mainly to open- and inactivated channels. Half-maximal activation
      voltage was slightly shifted towards more negative potentials. 5. Steady-state
      inactivation of HERG was not influenced by bertosamil. Bertosamil block elicited
      voltage-but no frequency-dependent effects. 6. In summary, bertosamil blocked the
      HERG potassium channel. These blocking properties may contribute to the anti
      arrhythmic effects of bertosamil in the treatment of atrial and particular
      ventricular arrhythmias.

PMID- 12208780
TI  - NCX 4016, a nitric oxide-releasing aspirin, modulates adrenergic vasoconstriction
      in the perfused rat tail artery.
AB  - 1. The ability of the nitric oxide (NO)-releasing aspirin, NCX 4016, to control
      vasoconstrictor responses induced by electrical field stimulation (TNS) or by
      exogenous norepinephrine (NE) was investigated in perfused rat tail artery with
      intact endothelium. 2. NCX 4016 (25, 50 and 100 microM) dose-dependently
      antagonized the vasoconstriction caused by TNS (from 0.5 to 64 Hz) and by NE
      (from 0.01 to 10 microM). The vasorelaxant activity of NCX 4016 (100 microM) in
      NE-precontracted arteries was concomitant with a marked increase of tissue cyclic
      GMP (4.9 fold, P<0.001) and was significantly antagonized by the inhibitors of
      soluble guanylate cyclase, methylene blue and 1H-[1,2,4]Oxadiazolo[4,3
      a]quinoxalin-1-one. 3. The effect of NCX 4016 was endothelium NO-independent
      since, in preparations perfused with N(G)-monomethyl-L-arginine (10 microM), this
      compound prevented the rise in basal perfusion pressure and reversed the
      accentuation of vasoconstrictor responses caused by NO synthase inhibition. 4.
      Aspirin-moiety released by NCX 4016 inhibited the 6-keto-PGF(1alpha) formation
      without interfering with the vasorelaxant activity of NCX 4016, while aspirin
      (100 microM) was devoid of any activity against vasoconstriction induced by both
      TNS and NE in perfused rat tail artery. 5. NCX 4016 moderated adrenergic
      vasoconstriction in perfused rat tail arteries by a direct donation of NO without
      involving the relaxant factors such as PGI(2) and NO from endothelial cells. 6.
      The results obtained with NCX 4016 in perfused rat tail artery bears some
      therapeutical potential in conditions associated with vascular smooth muscle
      hyperreactivity to adrenergic stimulation.

PMID- 12208781
TI  - Ligands for histamine H(3) receptors modulate cell proliferation and migration in
      rat oxyntic mucosa.
AB  - 1. (R)-alpha-methylhistamine, a selective agonist of histamine H(3) receptors,
      promotes mucus secretion and increases the number and volume of mucus-secreting
      cells. The hypothesis that the increased number of mucous cells could reside in
      an alteration of homeostasis in the gastric epithelium was investigated. 2. (R)
      alpha-methylhistamine was administered to rats 1 h (10-100 mg kg(-1) by
      intragastric and by intraperitoneal route) and 24 h (100 mg kg(-1) by
      intragastric route) prior to killing. The (S)-isomer of alpha-methylhistamine
      (55.4 mg kg(-1)), 100 times less potent than the (R)-isomer at H(3) receptors,
      and the H(3)-receptor agonist FUB 407 (9.14-91.35 mg kg(-1)) were
      intragrastically administered 1 h prior to killing. The H(1)-receptor antagonist
      mepyramine (30 mg kg(-1)), the H(2)-receptor antagonist famotidine (3 mg kg(-1)),
      and the H(3)-receptor antagonists ciproxifan (3 mg kg(-1)) and clobenpropit (30
      mg kg(-1)) were intragastrically administered 30 min before (R)-alpha
      methylhistamine. Gastric tissue was processed for histology and
      immunohistochemistry. 3. Within 1 h, (R)-alpha-methylhistamine and FUB 407 dose
      dependently increased the number of BrdU-positive cells and of apoptotic cells.
      (S)-alpha-methylhistamine failed to modify proliferation and apoptosis. The
      increase in proliferation by (R)-alpha-methylhistamine was reversed by ciproxifan
      and clobenpropit, but not by mepyramine and famotidine. 4. (R)-alpha
      methylhistamine accelerated the differentiation towards pit cells and their
      outward migration 24 h after its administration. These effects were counteracted
      by ciproxifan. The apoptosis rate was unaffected at 24 h. 5. These findings
      reveal a primary role of histamine H(3)-receptor ligands in modulating cell
      proliferation and migration in rat fundic mucosa.

PMID- 12208782
TI  - Gene expressions in Jurkat cells poisoned by a sulphur mustard vesicant and the
      induction of apoptosis.
AB  - 1. The sulphur mustard vesicant 2-chloroethylethyl sulphide (CEES) induced
      apoptosis in Jurkat cells. 2. Akt (PKB), a pivotal protein kinase which can block
      apoptosis and promotes cell survival, was identified to be chiefly down-regulated
      in a dose-dependent manner following CEES treatment. Functional analysis showed
      that the attendant Akt activity was simultaneously reduced. 3. PDK1, an upstream
      effector of Akt, was also down-regulated following CEES exposure, but two other
      upstream effectors of Akt, PI3-K and PDK2, remained unchanged. 4. The
      phosphorylation of Akt at Ser(473) and Thr(308) was significantly decreased
      following CEES treatment, reflecting the suppressed kinase activity of both PDK1
      and PDK2. 5. Concurrently, the anti-apoptotic genes, Bcl family, were down
      regulated, in sharp contrast to the striking up-regulation of some death
      executioner genes, caspase 3, 6, and 8. 6. Based on these findings, a model of
      CEES-induced apoptosis was established. These results suggest that CEES attacked
      the Akt pathway, directly or indirectly, by inhibiting Akt transcription,
      translation, and post-translation modification. 7. Taken together, upon exposure
      to CEES, apoptosis was induced in Jurkat cells via the down-regulation of the
      survival factors that normally prevent the activation of the death executioner
      genes, the caspases.

PMID- 12208783
TI  - Blocking action of chromanol 293B on the slow component of delayed rectifier K(+)
      current in guinea-pig sino-atrial node cells.
AB  - 1. In guinea-pig sino-atrial (SA) node cells the delayed rectifier K(+) current
      (I(K)) is composed of rapidly and slowly activating components of I(K) (I(Kr) and
      I(Ks), respectively). The present study was undertaken to characterize the
      blocking action of the chromanol derivative 293B on I(Ks) in guinea-pig SA node
      cells using whole-cell patch-clamp technique. 2. Bath application of 293B blocked
      I(Ks), elicited by 4-s depolarizing voltage pulses from a holding potential of 
      50 mV, under conditions in which the L-type Ca(2+) current (I(Ca,L)) and I(Kr)
      were inhibited; the effect was concentration-dependent with an IC(50) of 5.3
      microM, when evaluated by the decrease in the amplitude of I(Ks) tail current
      following 4-s depolarizing voltage steps to +50 mV. 3. The 293B block of I(Ks)
      progressed with time during depolarizing voltage steps with a more rapid block at
      higher concentrations. 4. The block of I(Ks) by 293B was fully reversed within a
      few minutes after washing off the drug, even when a maximal effect (a nearly full
      block) was achieved at high drug concentration (50 microM). 5. Bath application
      of 293B at 50 microM greatly and reversibly reduced the amplitude of I(Ks) which
      is maximally stimulated by beta-adrenergic agonist isoprenaline (1 microM), while
      the degree of 293B block of the isoprenaline-stimulated I(Ks) was slightly but
      significantly smaller than that of non-stimulated I(Ks) (94.0+/-0.98% block, n=6
      vs 99.4+/-0.45% block, n=6; P<0.01). 6. We conclude that, in guinea-pig SA node
      cells (i) 293B is a potent and fully reversible blocker of I(Ks) in control and
      during beta-adrenergic stimulation and (ii) block with 293B occurs in a time
      dependent manner during depolarizing voltage steps.

PMID- 12208784
TI  - Functional characterization and biomarker identification in the Brown Norway
      model of allergic airway inflammation.
AB  - 1. The antigen-induced inflammatory response in the Brown Norway rat is a model
      commonly used to assess the impact of novel compounds on airway eosinophilia. A
      detailed functional, cellular and molecular characterization of this model has
      not yet been performed within a single study. This information together with the
      temporal changes in this phenomenon should be known before this model can be
      used, with confidence, to elucidate the mechanisms of action of novel anti
      inflammatory drugs. 2. Antigen challenge caused an accumulation of eosinophils in
      lung tissue 24 h after challenge. Accumulation of CD2(+) T cells was not apparent
      until after 72 h. 3. Interestingly, mRNA for the Th2 type cytokines interleukin
      (IL)-4, IL-5 and IL-13 and eotaxin were elevated in lung tissue after challenge
      and the expression of IL-13 and eotaxin protein increased at around 8-12 h. The
      temporal changes in both the biomarker production and the functional responses
      are important factors to consider in protocol design prior to initiating a
      compound screening program. 4. A neutralising antibody (R73) against alphabeta
      TCR caused a significant reduction in T cell numbers accompanied by a significant
      suppression of eosinophil accumulation. 5. Airway hyperreactivity (AHR) was not
      apparent in this specific Brown Norway model in sensitized animals after a single
      or multiple challenges although eosinophil influx was seen in the same animals.
      6. In conclusion, this is a convenient pre-clinical model (incorporating the
      measurement of biomarkers and functional responses) for screening novel small
      molecule inhibitors and/or biotherapeutics targeted against T cell/eosinophil
      infiltration/activation.

PMID- 12208785
TI  - Bradykinin potentiation by ACE inhibitors: a matter of metabolism.
AB  - 1. Studies in isolated cells overexpressing ACE and bradykinin type 2 (B(2))
      receptors suggest that ACE inhibitors potentiate bradykinin by inhibiting B(2)
      receptor desensitization, via a mechanism involving protein kinase C (PKC) and
      phosphatases. Here we investigated, in intact porcine coronary arteries,
      endothelial ACE/B(2) receptor 'crosstalk' as well as bradykinin potentiation
      through neutral endopeptidase (NEP) inhibition. 2. NEP inhibition with
      phosphoramidon did not affect the bradykinin concentration-response curve (CRC),
      nor did combined NEP/ACE inhibition with omapatrilat exert a further leftward
      shift on top of the approximately 10 fold leftward shift of the bradykinin CRC
      observed with ACE inhibition alone. 3. In arteries that, following repeated
      exposure to 0.1 microM bradykinin, no longer responded to bradykinin
      ('desensitized' arteries), the ACE inhibitors quinaprilat and angiotensin-(1-7)
      both induced complete relaxation, without affecting the organ bath fluid levels
      of bradykinin. This phenomenon was unaffected by inhibition of PKC or
      phosphatases (with calphostin C and okadaic acid, respectively). 4. When using
      bradykinin analogues that were either completely or largely ACE-resistant
      ([Phe(8)psi(CH(2)-NH)Arg(9)]-bradykinin and [deltaPhe(5)]-bradykinin,
      respectively), the ACE inhibitor-induced shift of the bradykinin CRC was absent,
      and its ability to reverse desensitization was absent or significantly reduced,
      respectively. Caveolar disruption with filipin did not affect the quinaprilat
      induced effects. Filipin did however reduce the bradykinin-induced relaxation by
      approximately 25-30%, thereby confirming that B(2) receptor-endothelial NO
      synthase (eNOS) interaction occurs in caveolae. 5. In conclusion, in porcine
      arteries, in contrast to transfected cells, bradykinin potentiation by ACE
      inhibitors is a metabolic process, that can only be explained on the basis of ACE
      B(2) receptor co-localization on the endothelial cell membrane. NEP does not
      appear to affect the bradykinin levels in close proximity to B(2) receptors, and
      the ACE inhibitor-induced bradykinin potentiation precedes B(2) receptor coupling
      to eNOS in caveolae.

PMID- 12208786
TI  - Block of voltage-operated sodium channels by 2,6-dimethylphenol, a structural
      analogue of lidocaine's aromatic tail.
AB  - 1. The structural features that determine the state-dependent interaction of
      local anaesthetics with voltage-operated sodium channels are still a matter of
      debate. We have studied the blockade of sodium channels by 2,6-dimethylphenol, a
      phenol derivative which resembles the aromatic tail of lidocaine, etidocaine, and
      bupivacaine. 2. The effects of 2,6-dimethylphenol were studied on heterologously
      (HEK 293) expressed rat neuronal (rat brain IIA) and human skeletal muscle
      (hSkM1) sodium channels using whole-cell voltage-clamp experiments. 3. 2,6
      Dimethylphenol was effective in blocking whole-cell sodium inward currents. Its
      potency was comparable to the potency of lidocaine previously obtained with
      similar protocols by others. The IC(50) at -70 mV holding potential was 150 and
      187 microM for the skeletal muscle and the neuronal isoform, respectively. In
      both isoforms, the blocking potency increased with the fraction of inactivated
      channels at depolarized holding potentials. However, the block achieved at -70 mV
      with respect to -150 mV holding potential was significantly higher only in the
      skeletal muscle isoform. The estimated dissociation constant K(d) from the
      inactivated state was 25 microM and 28 microM in the skeletal muscle and the
      neuronal isoform, respectively. The kinetics of drug equilibration between
      resting and inactivated channel states were about 10 fold faster compared with
      lidocaine. 4. Our results show that the blockade induced by 2,6-dimethylphenol
      retains voltage-dependency, a typical feature of lidocaine-like local
      anaesthetics. This is consistent with the hypothesis that the 'aromatic tail'
      determines the state-dependent interaction of local anaesthetics with the sodium
      channel.

PMID- 12208788
TI  - Blunderbuss to Mickey Mouse: the evolution of antiarrhythmic targets.

PMID- 12208789
TI  - Current evaluation and management of patients with mitral stenosis.

PMID- 12208790
TI  - C-reactive protein is associated with subclinical epicardial coronary
      calcification in men and women: the Framingham Heart Study.
AB  - BACKGROUND: High C-reactive protein (CRP) levels are associated with an increased
      risk of cardiovascular events, even in apparently healthy individuals. It has not
      been established whether elevated CRP reflects an increased burden of subclinical
      coronary atherosclerosis. METHODS AND RESULTS: We studied a stratified random
      sample of 321 men and women (mean age 60 years) from the Framingham Heart Study
      who were free of clinically apparent cardiovascular disease. Subjects underwent
      electron-beam computed tomography to assess the number of coronary calcifications
      and the coronary artery calcification (CAC) Agatston score. Spearman correlation
      coefficients between CRP and CAC score were calculated and adjusted for age, age
      plus individual risk factors, and age plus the Framingham coronary heart disease
      risk score. For both sexes, CRP was significantly correlated with the Agatston
      score (age-adjusted Spearman correlation: 0.25 for men, 0.26 for women; both
      P<0.01). After adjustment for age and Framingham risk score, the correlation
      remained significant (P=0.01) for both sexes. Further adjustment for body mass
      index attenuated the correlation coefficient for women (0.14, P=0.09) but not for
      men (0.19, P<0.05). CONCLUSIONS: High CRP levels are associated with increased
      coronary calcification. Among individuals with elevated CRP, subclinical
      atherosclerosis may contribute to an increased risk for future cardiovascular
      events.

PMID- 12208791
TI  - Serum osteoprotegerin levels are associated with the presence and severity of
      coronary artery disease.
AB  - BACKGROUND: Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the
      tumor necrosis factor receptor family. OPG-deficient mice develop severe
      osteoporosis and medial arterial calcification of the aorta and renal arteries.
      OPG immunoreactivity was demonstrated in the normal blood vessels and in early
      atherosclerotic lesions. A recent clinical study suggests that there is a
      significant correlation between elevated serum OPG levels and cardiovascular
      mortality. We examined whether serum OPG levels are associated with the
      progression of coronary artery disease (CAD). METHODS AND RESULTS: Serum OPG
      levels were examined in 201 patients who underwent coronary angiography because
      of stable chest pain. The number of diseased vessels was used to represent the
      severity of CAD. Serum OPG levels were measured by ELISA and were significantly
      greater in patients with significant stenosis of the coronary arteries than in
      those without stenosis. As the severity of CAD increased, there was a significant
      increase in serum OPG levels. Serum OPG levels were 0.94+/-0.34, 1.04+/-0.38,
      1.19+/-0.38, and 1.44+/-0.54 ng/mL (medians 0.91, 0.99, 1.09, and 1.37) for the
      subjects with normal coronary arteries or luminal irregularities, 1-vessel
      disease, 2-vessel disease, and 3-vessel disease, respectively. Multivariate
      logistic regression analysis revealed that serum OPG levels were significantly
      associated with the presence of CAD [odds ratio, 5.2; 95% confidence interval,
      1.7 to 16.0]. CONCLUSIONS: Our data show that serum OPG levels are associated
      with the presence and severity of CAD, suggesting that OPG may be involved in the
      progression of CAD.

PMID- 12208792
TI  - Sustained reduction of in-stent neointimal growth with the use of a novel
      systemic nanoparticle paclitaxel.
AB  - BACKGROUND: Paclitaxel (PXL)-eluting stents in animals cause incomplete healing
      and, in some instances, a lack of sustained suppression of neointimal growth. The
      present study tested the efficacy of a novel systemic delivery nanoparticle PXL
      for reducing in-stent restenosis. METHODS AND RESULTS: A saline-reconstituted
      formulation of PXL stabilized by albumin nanoparticles (nPXL) was tested in 38
      New Zealand White rabbits receiving bilateral iliac artery stents. Doses of nPXL
      (1.0 to 5.0 mg/kg) were administered as a 10-minute intra-arterial infusion;
      control animals received vehicle (0.9% normal saline). In a follow-up chronic
      experiment, nPXL 5.0 mg/kg was given at stenting with or without an intravenous
      3.5-mg/kg repeat nPXL dose at 28 days; these studies were terminated at 3 months.
      At 28 days, mean neointimal thickness was reduced (P< or =0.02) by doses of nPXL
      > or =2.5 mg/kg with evidence of delayed healing. The efficacy of a single dose
      of nPXL 5.0 mg/kg, however, was lost by 90 days. In contrast, a second repeat
      dose of nPXL 3.5 mg/kg given 28 days after stenting resulted in sustained
      suppression of neointimal thickness at 90 days (P< or =0.009 versus single dose
      nPXL 5.0 mg/kg and controls) with nearly complete neointimal healing.
      CONCLUSIONS: Although systemic nPXL reduces neointimal growth at 28 days, a
      single repeat dose was required for sustained neointimal suppression. Thus, this
      novel systemic formulation of PXL may allow adjustment of dose at the stent
      treatment site and prove to be a useful adjunct for the clinical prevention of in
      stent restenosis.

PMID- 12208793
TI  - Smooth muscle progenitor cells in human blood.
AB  - BACKGROUND: Recent animal data suggest that vascular smooth muscle cells within
      the neointima of the vessel wall may originate from bone marrow, providing
      indirect evidence for circulating smooth muscle progenitor cells (SPCs). Evidence
      for circulating SPCs in human subjects does not exist, and the mechanism whereby
      such putative SPCs may home to sites of plaque formation is presently not
      understood but is likely to involve expression of specific surface adhesion
      molecules, such as integrins. In this study, we aimed to culture smooth muscle
      outgrowth cells (SOCs) from SPCs in human peripheral blood and characterize
      surface integrin expression on these cells. METHODS AND RESULTS: Human
      mononuclear cells isolated from buffy coat were seeded on collagen type 1 matrix
      and outgrowth cells selected in endothelial growth medium (EGM-2) or EGM-2 and
      platelet-derived growth factor BB. Selection in platelet-derived growth factor BB
      enriched medium caused rapid outgrowth and expansion of SOC to >40 population
      doublings in a 4-month period. These SOCs were positive for smooth muscle cell
      specific alpha actin (alphaSMA), myosin heavy chain, and calponin on
      immunofluorescence and Western blotting and were also positive for CD34, Flt1,
      and Flk1 receptor but negative for Tie-2 receptor expression, suggesting a
      potential bone marrow angioblastic origin. In contrast, endothelial outgrowth
      cells (EOCs) grown in EGM-2 alone and the initial MNC population were negative
      for these smooth muscle-specific markers. Integrin alpha5beta1 expression by FACS
      and Western blotting was significantly increased in SOCs compared with EOCs, and
      this was confirmed by 8-fold greater adhesion of SOC to fibronectin (P<0.001), an
      effect that could be decreased using an alpha5beta1 antibody. Finally, SOC showed
      a significantly greater in vitro proliferative potential compared with EOCs of
      similar passage (P<0.001). CONCLUSIONS: This study demonstrates for the first
      time outgrowth of smooth muscle cells with a specific growth, adhesion, and
      integrin profile from putative SPC in human blood. These data have implications
      for our understanding of adult vascular smooth muscle cell differentiation,
      proliferation, and homing.

PMID- 12208794
TI  - Death following creatine kinase-MB elevation after coronary intervention:
      identification of an early risk period: importance of creatine kinase-MB level,
      completeness of revascularization, ventricular function, and probable benefit of
      statin therapy.
AB  - BACKGROUND: Creatine kinase (CK)-MB elevation after percutaneous coronary
      intervention (PCI) has been associated with subsequent cardiac death. The
      patients at risk, the timing of risk, and potential treatment implications are
      uncertain. METHODS AND RESULTS: Eight thousand, four hundred nine consecutive non
      acute myocardial infarction patients with successful PCI and no emergency
      surgery or Q-wave myocardial infarction were followed for 38+/-25 months; 1446
      (17.2%) had post-PCI CK-MB above normal on routine ascertainment. Patients were
      prospectively stratified into those with CK-MB 1 to 5x or CK-MB >5x normal. No
      patient with CK-MB 1 to 5x normal died during the first week after PCI, and
      excess risk of early death for patients with CK-MB elevation occurred primarily
      in the first 3 to 4 months. The actuarial 4-month risk of death was 8.9%, 1.9%,
      and 1.2% for patients with CK-MB >5x, CK-MB 1 to 5x, and CK-MB < or =1x normal
      (P<0.001). Death within 4 months was independently correlated with the degree of
      CK-MB elevation, creatinine > or =2 mg%, post-PCI C-reactive protein, low
      ejection fraction, age, and congestive heart failure class (P<0.01 for all). In a
      matched subset analysis, incomplete revascularization (P<0.001), congestive heart
      failure class (P=0.005), and no statin treatment at hospital discharge (P=0.009)
      were associated with death. CONCLUSIONS: Patients with CK-MB elevation after PCI
      are at excess risk of death for 3 to 4 months, although prolonging
      hospitalization for CK-MB 1 to 5x is unlikely to modify risk. CK-MB >5x normal,
      incomplete revascularization, elevated C-reactive protein, heart failure, the
      elderly, and hospital discharge without on statin therapy increases risk. Several
      of these factors suggest that inflammation may play a part in the excess risk of
      death.

PMID- 12208795
TI  - Evidence for an independent and cumulative effect of postprandial
      hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative
      stress generation: effects of short- and long-term simvastatin treatment.
AB  - BACKGROUND: Postprandial hypertriglyceridemia and hyperglycemia are considered
      risk factors for cardiovascular disease. Evidence suggests that postprandial
      hypertriglyceridemia and hyperglycemia induce endothelial dysfunction through
      oxidative stress; however, the distinct role of these two factors is a matter of
      debate. METHODS AND RESULTS: Thirty type 2 diabetic patients and 20 normal
      subjects ate 3 different meals: a high-fat meal; 75 g glucose alone; and high-fat
      meal plus glucose. Glycemia, triglyceridemia, nitrotyrosine, and endothelial
      function were assayed during the tests. Subsequently, diabetics took 40 mg/d
      simvastatin or placebo for 12 weeks. The 3 tests were performed again at
      baseline, between 3 to 6 days after the start, and at the end of each study. High
      fat load and glucose alone produced a decrease of endothelial function and an
      increase of nitrotyrosine in normal and diabetic subjects. These effects were
      more pronounced when high fat and glucose were combined. Short-term simvastatin
      treatment had no effect on lipid parameters but reduced the effect on endothelial
      function and nitrotyrosine observed during each different test. Long-term
      simvastatin treatment was accompanied by a lower increase in postprandial
      triglycerides, which was followed by smaller variations of endothelial function
      and nitrotyrosine during the tests. CONCLUSIONS: This study shows an independent
      and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on
      endothelial function, suggesting oxidative stress as common mediator of such
      effect. Simvastatin shows a beneficial effect on oxidative stress and endothelial
      dysfunction, which may be ascribed to a direct effect as well as the lipid
      lowering action of the drug.

PMID- 12208796
TI  - Effect of treatment for Chlamydia pneumoniae and Helicobacter pylori on markers
      of inflammation and cardiac events in patients with acute coronary syndromes:
      South Thames Trial of Antibiotics in Myocardial Infarction and Unstable Angina
      (STAMINA).
AB  - BACKGROUND: Infection with Helicobacter pylori and Chlamydia pneumoniae is
      associated with coronary heart disease. We conducted an intervention study using
      antibiotics against these bacteria in patients with acute coronary syndromes to
      determine whether antibiotics reduce inflammatory markers and adverse cardiac
      events. METHODS AND RESULTS: Patients (n=325) admitted with acute myocardial
      infarction or unstable angina (acute coronary syndromes) were randomized to
      receive a 1-week course of 1 of 3 treatment regimens: (1) placebo; (2)
      amoxicillin (500 mg twice daily), metronidazole (400 mg twice daily), and
      omeprazole (20 mg twice daily); or (3) azithromycin (500 mg once daily),
      metronidazole (400 mg twice daily), and omeprazole (20 mg twice daily). Serum
      fibrinogen, white cell count, and high-sensitivity C-reactive protein were
      measured at study entry and at 1, 3, and 12 months during follow-up. Cardiac
      death and readmission with acute coronary syndrome were considered clinical end
      points. Patients were followed for 1 year. C-reactive protein levels were reduced
      (P=0.03) in unstable angina patients receiving amoxicillin, and fibrinogen was
      reduced in both patient groups receiving antibiotics (P=0.06). There were 17
      cardiac deaths and 71 readmissions with acute coronary syndrome. No difference in
      frequency or timing of end points was observed between the 2 antibiotic groups.
      At 12 weeks, there was a 36% reduction in all end points in patients receiving
      antibiotics compared with placebo (P=0.02). This reduction persisted during the 1
      year follow-up. Neither C pneumoniae nor H pylori antibody status was
      significantly related to response to treatment. CONCLUSIONS: Antibiotic treatment
      significantly reduced adverse cardiac events in patients with acute coronary
      syndromes, but the effect was independent of H pylori or C pneumoniae
      seropositivity.

PMID- 12208797
TI  - Effect of transdermal estradiol and oral conjugated estrogen on C-reactive
      protein in retinoid-placebo trial in healthy women.
AB  - BACKGROUND: The increase in C-reactive protein (CRP) during oral conjugated
      equine estrogen (CEE) may explain the initial excess of cardiovascular disease
      observed in clinical studies. Because the effect of transdermal estradiol (E2) on
      CRP is unclear, we compared CRP changes after 6 and 12 months of transdermal E2
      and oral CEE in a randomized 2x2 retinoid-placebo trial. METHODS AND RESULTS: A
      total of 189 postmenopausal women were randomized to 50 microg/d transdermal E2
      and 100 mg BID of the retinoid fenretinide (n=45), 50 microg/d transdermal E2 and
      placebo (n=49), 0.625 mg/d oral CEE and 100 mg BID fenretinide (n=46), or 0.625
      mg/d oral CEE and placebo (n=49) for 1 year. Sequential medroxyprogesterone
      acetate was added in each group. Relative to baseline, CRP increased by 10% (95%
      CI -9% to 33%) and by 48% (95% CI 22% to 78%) after 6 months of transdermal E2
      and oral CEE, respectively. The corresponding figures at 12 months were 3% (95%
      CI -14% to 23%) for transdermal E2 and 64% (95% CI 38% to 96%) for oral CEE.
      Fenretinide did not change CRP levels at 6 and 12 months relative to placebo.
      Relative to oral CEE, the mean change in CRP after 12 months of transdermal E2
      was -48% (95% CI -85% to -7%, P=0.012), whereas fenretinide was associated with a
      mean change of -1% (95% CI -34% to 40%, P=0.79) compared with placebo.
      CONCLUSIONS: In contrast to oral CEE, transdermal E2 does not elevate CRP levels
      up to 12 months of treatment. The implications for early risk of coronary heart
      disease require further studies.

PMID- 12208798
TI  - Perceived mental stress and mortality from cardiovascular disease among Japanese
      men and women: the Japan Collaborative Cohort Study for Evaluation of Cancer Risk
      Sponsored by Monbusho (JACC Study).
AB  - BACKGROUND: Perceived mental stress has been associated with risk of coronary
      heart disease (CHD) in white men, but no prospective data are available for other
      ethnic groups. METHODS AND RESULTS: From 1988 to 1990, a total of 73 424 Japanese
      (30 180 men and 43 244 women), aged 40 to 79 years, without a history of stroke,
      CHD, or cancer completed a lifestyle questionnaire including perception of mental
      stress under the Japan Collaborative Cohort Study for Evaluation of Cancer Risk
      Sponsored by Monbusho (JACC Study). Systematic surveillance was completed until
      the end of 1997, with a 580 378 person-year follow-up, and the underlying causes
      of death were determined according to the International Classification of
      Diseases, 10th revision. For women, there were 316 with total stroke, 113 with
      CHD, and 643 with total cardiovascular disease (CVD); for men, there were 341,
      168, and 778, respectively. Women who reported high stress had a 2-fold higher
      age-adjusted risk of mortality from total stroke and CHD and 1.5-fold higher risk
      of total CVD compared with those who reported low stress. Further adjustment for
      known cardiovascular risk factors and selected psychological variables did not
      alter the associations materially. The multivariate relative risk for women who
      perceived high stress versus low stress was 2.24 (95% CI 1.52 to 3.31, P<0.001)
      for total stroke, 2.28 (95% CI 1.17 to 4.43, P=0.02) for CHD, and 1.64 (95% CI
      1.25 to 2.16, P<0.001) for total CVD. For men, these relations were generally
      weaker but suggestive of myocardial infarction. CONCLUSIONS: Perceived mental
      stress was associated with increased mortality from stroke for women and with CHD
      for men and women.

PMID- 12208799
TI  - Left ventricular systolic unloading and augmentation of intracoronary pressure
      and Doppler flow during enhanced external counterpulsation.
AB  - BACKGROUND: Enhanced external counterpulsation (EECP) is a noninvasive, pneumatic
      technique that provides beneficial effects for patients with chronic, symptomatic
      angina pectoris. However, the physiological effects of EECP have not been studied
      directly. We examined intracoronary and left ventricular hemodynamics in the
      cardiac catheterization laboratory during EECP. METHODS AND RESULTS: Ten patients
      referred for diagnostic evaluation underwent left heart catheterization and
      coronary angiography from the radial artery. At baseline and then during EECP,
      central aortic pressure, intracoronary pressure, and intracoronary Doppler flow
      velocity were measured using a coronary catheter, a sensor-tipped high-fidelity
      pressure guidewire, and a Doppler flow guidewire, respectively. Similar to
      changes in aortic pressure, EECP resulted in a dramatic increase in diastolic
      (71+/-10 mm Hg at baseline to 137+/-21 mm Hg during EECP; +93%; P<0.0001) and
      mean intracoronary pressures (88+/-9 to 102+/-16 mm Hg; +16%; P=0.006) with a
      decrease in systolic pressure (116+/-20 to 99+/-26 mm Hg; -15%; P=0.002). The
      intracoronary Doppler measure of average peak velocity increased from 11+/-5 cm/s
      at baseline to 23+/-5 cm/s during EECP (+109%; P=0.001). The TIMI frame count, a
      quantitative angiographic measure of coronary flow, showed a 28% increase in
      coronary flow during EECP compared with baseline (P=0.001). CONCLUSIONS: EECP
      unequivocally and significantly increases diastolic and mean pressures and
      reduces systolic pressure in the central aorta and the coronary artery. Coronary
      artery flow, determined by both Doppler and angiographic techniques, is increased
      during EECP. The combined effects of systolic unloading and increased coronary
      perfusion pressure provide evidence that EECP may serve as a potential mechanical
      assist device.

PMID- 12208800
TI  - Results of Prevention of REStenosis with Tranilast and its Outcomes (PRESTO)
      trial.
AB  - BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) is a major
      problem affecting 15% to 30% of patients after stent placement. No oral agent has
      shown a beneficial effect on restenosis or on associated major adverse
      cardiovascular events. In limited trials, the oral agent tranilast has been shown
      to decrease the frequency of angiographic restenosis after PCI. METHODS AND
      RESULTS: In this double-blind, randomized, placebo-controlled trial of tranilast
      (300 and 450 mg BID for 1 or 3 months), 11 484 patients were enrolled. Enrollment
      and drug were initiated within 4 hours after successful PCI of at least 1 vessel.
      The primary end point was the first occurrence of death, myocardial infarction,
      or ischemia-driven target vessel revascularization within 9 months and was 15.8%
      in the placebo group and 15.5% to 16.1% in the tranilast groups (P=0.77 to 0.81).
      Myocardial infarction was the only component of major adverse cardiovascular
      events to show some evidence of a reduction with tranilast (450 mg BID for 3
      months): 1.1% versus 1.8% with placebo (P=0.061 for intent-to-treat population).
      The primary reason for not completing treatment was > or =1 hepatic laboratory
      test abnormality (11.4% versus 0.2% with placebo, P<0.01). In the angiographic
      substudy composed of 2018 patients, minimal lumen diameter (MLD) was measured by
      quantitative coronary angiography. At follow-up, MLD was 1.76+/-0.77 mm in the
      placebo group, which was not different from MLD in the tranilast groups (1.72 to
      1.78+/-0.76 to 80 mm, P=0.49 to 0.89). In a subset of these patients (n=1107),
      intravascular ultrasound was performed at follow-up. Plaque volume was not
      different between the placebo and tranilast groups (39.3 versus 37.5 to 46.1
      mm(3), respectively; P=0.16 to 0.72). CONCLUSIONS: Tranilast does not improve the
      quantitative measures of restenosis (angiographic and intravascular ultrasound)
      or its clinical sequelae.

PMID- 12208801
TI  - Ventricular remodeling does not accompany the development of heart failure in
      diabetic patients after myocardial infarction.
AB  - BACKGROUND: Diabetic patients are at increased risk for heart failure (HF) and
      other adverse events after myocardial infarction (MI). Left ventricular (LV)
      enlargement after MI is also associated with the same increased risk. We used
      data from the Survival and Ventricular Enlargement (SAVE) echocardiographic
      substudy to test the hypothesis that diabetes was associated with increased LV
      enlargement after MI. METHODS AND RESULTS: Four hundred twelve nondiabetic and
      100 diabetic patients underwent echocardiographic assessment at baseline and 3
      months, 1 year, and 2 years after MI. HF developed in 30% of diabetic and 17% of
      nondiabetic patients during follow-up (P<0.001). Baseline LV diastolic size,
      ejection fraction, and infarct segment length were similar between diabetic and
      nondiabetic patients. Diabetic patients demonstrated less LV enlargement between
      baseline and 2 years than nondiabetic patients (0.9+/-11.1 cm2 versus 3.8+/-10.9
      cm2, P=0.047). In patients who developed HF, LV diastolic dilatation (10.0+/-12.4
      cm2 versus 3.7+/-13.1 cm2, P=0.06) and systolic dilatation (4.6+/-11.8 versus
      0.91+/-12.1, P=0.017) were greater in nondiabetic than in diabetic patients. LV
      dilatation between baseline and 2 years was a predictor of HF in nondiabetic
      patients, but not in diabetic patients, even after excluding patients with
      recurrent MI and adjusting for history of hypertension, prior MI, age, treatment
      group, and smoking. Diabetes modified the relationship between ventricular
      enlargement and the risk of HF (P=0.011). CONCLUSIONS: The increased incidence of
      HF after MI in diabetic patients is not explained by a greater propensity for LV
      remodeling.

PMID- 12208802
TI  - Segmental ostial ablation to isolate the pulmonary veins during atrial
      fibrillation: feasibility and mechanistic insights.
AB  - BACKGROUND: The purpose of this study was to determine the feasibility and
      mechanistic implications of segmental pulmonary vein (PV) ostial ablation during
      atrial fibrillation (AF). METHODS AND RESULTS: Forty consecutive patients
      underwent PV isolation for AF. Among 125 PVs targeted for isolation, ablation was
      performed during AF in 70 veins and during sinus rhythm in 55 veins. A decapolar
      Lasso catheter was positioned near the ostium. During AF, ostial ablation was
      performed near the Lasso catheter electrodes that recorded a tachycardia with a
      cycle length shorter than in the adjacent left atrium. During sinus rhythm,
      ostial ablation was guided by PV potentials. Complete PV isolation was achieved
      in 70 PVs (100%) ablated during AF and in 53 PVs (96%) ablated during sinus
      rhythm (P=0.4). The mean durations of radiofrequency energy needed for isolation
      were 7.4+/-4.4 and 5.2+/-3.9 minutes during AF and sinus rhythm, respectively
      (P<0.01). Before ablation, an immediate recurrence of AF (IRAF), occurred after
      cardioversion in 18 of 40 patients, and IRAF was consistently abolished by PV
      isolation. The probability of AF termination during isolation of a PV was
      directly related to the extent of tachycardia in that vein. As more PVs were
      isolated, induction of persistent AF by rapid pacing became less likely.
      CONCLUSIONS: Segmental ostial ablation guided by PV tachycardia during AF is
      feasible and as efficacious as during sinus rhythm. The responses to
      cardioversion, ablation, and rapid pacing observed in this study imply that IRAF
      is triggered by the PVs and that PV tachycardias may play an important role in
      the perpetuation of AF.

PMID- 12208803
TI  - Importance of cardiac troponins I and T in risk stratification of patients with
      acute pulmonary embolism.
AB  - BACKGROUND: Assessment of risk and appropriate management of patients with acute
      pulmonary embolism (PE) remains a challenge. Cardiac troponins I (cTnI) and T
      (cTnT) are reliable indicators of myocardial injury and may be associated with
      right ventricular dysfunction in PE. METHODS AND RESULTS: The present prospective
      study included 106 consecutive patients with confirmed acute PE. cTnI was
      elevated (> or =0.07 ng/mL) in 43 patients (41%), and cTnT (> or =0.04 ng/mL) was
      elevated in 39 (37%). Elevation of cTnI or cTnT was significantly associated with
      echocardiographically detected right ventricular dysfunction (P=0.001 and P<0.05,
      respectively). Moreover, a significant correlation was found between elevation of
      cTnI or cTnT and the two major end points overall mortality and complicated in
      hospital course. The negative predictive value of cardiac troponins for major
      clinical events was 92% to 93%. Importantly, there was obvious escalation of in
      hospital mortality, the rate of complications, and the incidence of recurrent PE,
      when patients with high troponin concentrations (cTnI >1.5; cTnT >0.1 ng/mL) were
      compared with those with only moderately elevated levels (cTnI, 0.07 to 1.5;
      cTnT, 0.04 to 0.1 ng/mL). Logistic regression analysis confirmed that the
      mortality risk (OR) was significantly elevated only in patients with high cTnI
      (P=0.019) or cTnT (P=0.038) levels. Furthermore, the risk of a complicated in
      hospital course was almost 5 times higher (15.47 versus 3.16) in the high-cTnI
      group compared with patients with moderate cTnI elevation. CONCLUSIONS: Our
      results indicate that cTnI and cTnT may be a novel, particularly useful tool for
      optimizing the management strategy in patients with acute PE.

PMID- 12208804
TI  - Drug-induced long-QT syndrome associated with a subclinical SCN5A mutation.
AB  - BACKGROUND: Subclinical mutations in genes associated with the congenital long-QT
      syndromes (LQTS) have been suggested as a risk factor for drug-induced LQTS and
      accompanying life-threatening arrhythmias. Recent studies have identified genetic
      variants of the cardiac K+ channel genes predisposing affected individuals to
      acquired LQTS. We have identified a novel Na+ channel mutation in an individual
      who exhibited drug-induced LQTS. METHODS AND RESULTS: An elderly Japanese woman
      with documented QT prolongation and torsade de pointes during treatment with the
      prokinetic drug cisapride underwent mutational analysis of LQTS-related genes. A
      novel missense mutation (L1825P) was identified within the C-terminus region of
      the cardiac Na+ channel (SCN5A). The L1825P channel heterologously expressed in
      tsA-201 cells showed Na+ current with slow decay and a prominent tetrodotoxin
      sensitive noninactivating component, similar to the gain-of-function phenotype
      most commonly observed for SCN5A-associated congenital LQTS (LQT3). In addition,
      L1825P exhibited loss of function Na+ channel features characteristic of Brugada
      syndrome. Peak Na+ current density observed in cells expressing L1825P was
      significantly diminished, and the voltage dependence of activation and
      inactivation was shifted toward more positive and negative potentials,
      respectively. CONCLUSIONS: This study demonstrates that subclinical mutations in
      the LQTS-related gene SCN5A may predispose certain individuals to drug-induced
      cardiac arrhythmias.

PMID- 12208805
TI  - Effect of hyperhomocysteinemia on plasma or tissue adenosine levels and renal
      function.
AB  - BACKGROUND: Hyperhomocysteinemia (hHcys) is considered an independent risk factor
      of cardiovascular diseases. Recent studies in our laboratory have shown that
      hHcys produced glomerular dysfunction and sclerosis independently of
      hypertension. However, the mechanism mediating these pathogenic effects of
      homocysteine (Hcys) is poorly understood. Because Hcys and adenosine (Ado) are
      simultaneously produced via hydrolysis of S-adenosylhomocysteine (SAH), we
      hypothesized that hHcys may produce its pathogenic effects by decrease in plasma
      or tissue Ado concentrations. METHODS AND RESULTS: L-Hcys (1.5 micromol/min per
      kilogram) was infused intravenously for 60 minutes to produce acute hHcys in
      Sprague-Dawley rats. Plasma Hcys levels increased from 6.7+/-0.4 to 14.7+/-0.5
      micromol/L, but Ado decreased from 141.7+/-15.1 to 52.4+/-6.8 nmol/L in these
      rats with acute hHcys. This hHcys-induced reduction of Ado was also observed in
      the kidney dialysate. In rats with chronic hHcys, plasma Ado levels were also
      significantly decreased. By kinetic analysis of the enzyme activities, decrease
      in renal Ado levels in hHcys was shown to be associated with inhibition of SAH
      hydrolase but not 5'-nucleotidase. Functionally, intravenous infusion of Hcys was
      found to decrease renal blood flow, glomerular filtration rate, and sodium and
      water excretion, which could be blocked by the Ado receptor antagonist 8-SPT.
      CONCLUSIONS: These results strongly suggest that hHcys decreases plasma and
      tissue Ado concentrations associated with inhibition of SAH hydrolase. Decrease
      in plasma and tissue Ado may be an important mechanism mediating the pathogenic
      effects of Hcys.

PMID- 12208806
TI  - Effect of low-dose aspirin on vascular inflammation, plaque stability, and
      atherogenesis in low-density lipoprotein receptor-deficient mice.
AB  - BACKGROUND: Atherosclerosis is a complex vascular inflammatory disease. Low-dose
      aspirin is a mainstay in the prevention of vascular complications of
      atherosclerosis. We wished to determine the effect of low-dose aspirin on
      vascular inflammation, plaque composition, and atherogenesis in LDL receptor
      deficient mice fed a high fat diet. METHODS AND RESULTS: In LDL receptor
      deficient mice fed a high fat diet compared with control mice, low-dose aspirin
      induced a significant decrease in circulating levels and vascular formation of
      soluble intercellular molecule-1, monocyte chemoattractant protein-1, tumor
      necrosis factor-alpha, interleukin-12p 40, without affecting lipid levels. This
      was associated with significant reduction of the nuclear factor kappaB activity
      in the aorta. Low-dose aspirin also significantly reduced the extent of
      atherosclerosis. Finally, aortic vascular lesions of the aspirin-treated animals
      showed 57% reduction (P<0.05) in the amount of macrophage cells, 77% increase in
      smooth muscle cells (P<0.05), and 23% increase in collagen (P<0.05). CONCLUSIONS:
      Our results suggest that in murine atherosclerosis, low-dose aspirin suppresses
      vascular inflammation and increases the stability of atherosclerotic plaques,
      both of which, together with its antiplatelet activity, contribute to its
      antiatherogenic effect. We conclude that low-dose aspirin might be rationally
      evaluated in the progression and evolution of human atherosclerotic plaque.

PMID- 12208807
TI  - Calmodulin kinase II and arrhythmias in a mouse model of cardiac hypertrophy.
AB  - BACKGROUND: Calmodulin kinase (CaMK) II is linked to arrhythmia mechanisms in
      cellular models where repolarization is prolonged. CaMKII upregulation and
      prolonged repolarization are general features of cardiomyopathy, but the role of
      CaMKII in arrhythmias in cardiomyopathy is unknown. METHODS AND RESULTS: We
      studied a mouse model of cardiac hypertrophy attributable to transgenic (TG)
      overexpression of a constitutively active form of CaMKIV that also has increased
      endogenous CaMKII activity. ECG-telemetered TG mice had significantly more
      arrhythmias than wild-type (WT) littermate controls at baseline, and arrhythmias
      were additionally increased by isoproterenol. Arrhythmias were significantly
      suppressed by an inhibitory agent targeting endogenous CaMKII. TG mice had longer
      QT intervals and action potential durations than WT mice, and TG cardiomyocytes
      had frequent early afterdepolarizations (EADs), a hypothesized mechanism for
      triggering arrhythmias. EADs were absent in WT cells before and after
      isoproterenol, whereas EAD frequency was unaffected by isoproterenol in TG mice.
      L-type Ca2+ channels (LTTCs) can activate EADs, and LTCC opening probability (Po)
      was significantly higher in TG than WT cardiomyocytes before and after
      isoproterenol. A CaMKII inhibitory peptide equalized TG and WT LTCC Po and
      eliminated EADs, whereas a peptide antagonist of the Na+/Ca2+ exchanger current,
      also hypothesized to support EADs, was ineffective. CONCLUSIONS: These findings
      support the hypothesis that CaMKII is a proarrhythmic signaling molecule in
      cardiac hypertrophy in vivo. Cellular studies point to EADs as a triggering
      mechanism for arrhythmias but suggest that the increase in arrhythmias after beta
      adrenergic stimulation is independent of enhanced EAD frequency.

PMID- 12208808
TI  - Stem cell-derived cardiomyocytes demonstrate arrhythmic potential.
AB  - BACKGROUND: Cardiomyocytes (CMs) derived from pluripotent embryonic stem cells
      (ESCs) and embryonal carcinoma cells (ECCs) have some but not all characteristics
      of adult myocytes. ESCs have shown the ability to engraft in areas of myocardial
      damage, which suggests their use in cell transplantation therapy for
      cardiomyopathy. We studied the arrhythmogenic properties of CMs differentiated
      from mouse ESCs and ECCs. METHODS AND RESULTS: CMs derived in vitro were studied
      in the whole-cell patch-clamp mode. CMs from both sources showed action potential
      (AP) morphology heterogeneity, with reduced maximum upstroke velocities (dV/dt)
      and prolonged AP durations. CMs demonstrated prolonged, spontaneous electrical
      activity in culture. Frequent triggered activity was observed with and without
      pharmacological enhancement. Phase 2 or 3 early afterdepolarizations could be
      induced easily by Bay K8644 plus tetraethylammonium chloride (TEA) or [TEA]o
      after Cs+ replacement for [K+]i, respectively. A combination of bradycardic
      stimulation, hypokalemia, and quinidine resulted in early afterdepolarizations.
      Delayed afterdepolarizations could be induced easily and reversibly by
      hypercalcemia or isoproterenol. CONCLUSIONS: ESCs or ECCs differentiated into at
      least 3 AP phenotypes. CMs showed spontaneous activity, low dV/dt, prolonged AP
      duration, and easily inducible triggered arrhythmias. These findings raise
      caution about the use of totipotent ESCs in cell transplantation therapy, because
      they may act as an unanticipated arrhythmogenic source from any of the 3 classic
      mechanisms (reentry, automaticity, or triggered activity).

PMID- 12208809
TI  - Images in cardiovascular medicine. Improved preoperative assessment of papillary
      fibroelastoma by dynamic three-dimensional echocardiography.

PMID- 12208810
TI  - Images in cardiovascular medicine. Time-lapse study with high speed video camera
      in the early embryonic chick heart to visualize a time window of normal and
      abnormal heart development.

PMID- 12208812
TI  - Nontarget effects--the Achilles' heel of biological control? Retrospective
      analyses to reduce risk associated with biocontrol introductions.
AB  - Controversy exists over ecological risks in classical biological control. We
      reviewed 10 projects with quantitative data on nontarget effects. Ten patterns
      emerged: (a) Relatives of the pest are most likely to be attacked; (b) host
      specificity testing defines physiological host range, but not ecological range;
      (c) prediction of ecological consequences requires population data; (d) level of
      impact varied, often in relation to environmental conditions; (e) information on
      magnitude of nontarget impact is sparse; (f) attack on rare native species can
      accelerate their decline; (g) nontarget effects can be indirect; (h) agents
      disperse from agroecosystems; (i) whole assemblages of species can be perturbed;
      and (j) no evidence on adaptation is available in these cases. The review leads
      to six recommendations: Avoid using generalists or adventive species; expand host
      specificity testing; incorporate more ecological information; consider ecological
      risk in target selection; prioritize agents; and pursue genetic data on
      adaptation. We conclude that retrospective analyses suggest clear ways to further
      increase future safety of biocontrol.

PMID- 12208813
TI  - Comparative social biology of basal taxa of ants and termites.
AB  - Lacking a comprehensive fossil record, solitary representatives of the taxa,
      and/or a definitive phylogeny of closely related insects, comparison of the life
      history and social biology of basal, living groups is one of the few available
      options for developing inferences regarding the early eusocial evolution of ants
      and termites. Comparisons of a select group of basal formicid and isopteran taxa
      suggest that the reproductive organization of colonies and their patterns of
      division of labor were particularly influenced, in both groups, by nesting and
      feeding ecology. Opportunities for serial inheritance of the nest structure and
      colony population by kin may have been significant in the evolution of multiple
      reproductive forms and options. Disease has been a significant factor in the
      evolution of social organization in ants and termites, but the adaptive
      mechanisms of infection control differ. Evaluations of the convergent and
      divergent social biology of the two taxa can generate novel domains of research
      and testable hypotheses.

PMID- 12208814
TI  - Genomics in pure and applied entomology.
AB  - Genomics is the study of the structure and function of the genome: the set of
      genetic information encoded in the DNA of the nucleus and organelles of an
      organism. It is a dynamic field that combines traditional paths of inquiry with
      new approaches that would have been impossible without recent technological
      developments. Much of the recent focus has been on obtaining the sequence of
      entire genomes, determining the order and organization of the genes, and
      developing libraries that provide immediate physical access to any desired DNA
      fragment. This has enabled functional studies on a genome-wide level, including
      analysis of the genetic basis of complex traits, quantification of global
      patterns of gene expression, and systematic gene disruption projects. The
      successful contribution of genomics to problems in applied entomology requires
      the cooperation of the private and public sectors to build upon the knowledge
      derived from the Drosophila genome and effectively develop models for other
      insect Orders.

PMID- 12208815
TI  - Management of agricultural insects with physical control methods.
AB  - Ideally, integrated pest management should rely on an array of tactics. In
      reality, the main technologies in use are synthetic pesticides. Because of well
      documented problems with reliance on synthetic pesticides, viable alternatives
      are sorely needed. Physical controls can be classified as passive (e.g.,
      trenches, fences, organic mulch, particle films, inert dusts, and oils), active
      (e.g., mechanical, polishing, pneumatic, impact, and thermal), and miscellaneous
      (e.g., cold storage, heated air, flaming, hot-water immersion). Some physical
      methods such as oils have been used successfully for preharvest treatments for
      decades. Another recently developed method for preharvest situations is particle
      films. As we move from production to the consumer, legal constraints restrict the
      number of options available. Consequently, several physical control methods are
      used in postharvest situations. Two noteworthy examples are the entoleter, an
      impacting machine used to crush all insect stages in flour, and hot-water
      immersion of mangoes, used to kill tephritid fruit fly immatures in fruit. The
      future of physical control methods will be influenced by sociolegal issues and by
      new developments in basic and applied research.

PMID- 12208816
TI  - Molecular systematics of Anopheles: from subgenera to subpopulations.
AB  - The century-old discovery of the role of Anopheles in human malaria transmission
      precipitated intense study of this genus at the alpha taxonomy level, but until
      recently little attention was focused on the systematics of this group. The
      application of molecular approaches to systematic problems ranging from
      subgeneric relationships to relationships at and below the species level is
      helping to address questions such as anopheline phylogenetics and biogeography,
      the nature of species boundaries, and the forces that have structured genetic
      variation within species. Current knowledge in these areas is reviewed, with an
      emphasis on the Anopheles gambiae model. The recent publication of the genome of
      this anopheline mosquito will have a profound impact on inquiries at all
      taxonomic levels, supplying better tools for estimating phylogeny and population
      structure in the short term, and ultimately allowing the identification of genes
      and/or regulatory networks underlying ecological differentiation, speciation, and
      vectorial capacity.

PMID- 12208817
TI  - Male accessory gland secretions: modulators of female reproductive physiology and
      behavior.
AB  - Secretions of male accessory glands contain a variety of bioactive molecules.
      When transferred during mating, these molecules exert wide-ranging effects on
      female reproductive activity and they improve the male's chances of siring a
      significant proportion of the female's offspring. The accessory gland secretions
      may affect virtually all aspects of the female's reproductive activity. The
      secretions may render her unwilling or unable to remate for some time,
      facilitating sperm storage and ensuring that any eggs laid will be fertilized by
      that male's sperm. They may stimulate an increase in the number and rate of
      development of eggs and modulate ovulation and/or oviposition. Antimicrobial
      agents in the secretions ensure that the female reproductive tract is a
      hospitable environment during sperm transfer. In a few species the secretions
      include noxious chemicals. These are sequestered by developing eggs that are
      thereby protected from predators and pathogens when laid.

PMID- 12208818
TI  - Feather mites (Acari: Astigmata): ecology, behavior, and evolution.
AB  - Birds host many lineages of symbiotic mites, but the greatest diversity is shown
      by the three superfamilies of astigmatan feather mites: Analgoidea,
      Pterolichoidea, and Freyanoidea. Members of this diphyletic grouping have
      colonized all parts of the avian integument from their ancestral nidicolous
      habitat. Whereas some clearly feed on feather pith or skin, acting as parasites,
      other feather mites are paraphages and consume feather oils without causing
      structural damage. Sexual dimorphism in feather mites is often extreme, and
      little is known of the function of many elaborate male structures. Abundance and
      location of vane-dwelling mites is affected by season, temperature, light,
      humidity, and host body condition. Because transmission between hosts usually
      depends on host body contact, it is unsurprising that feather mite phylogeny
      often parallels host phylogeny; however, recent cladistic analyses have also
      found evidence of host-jumping and "missing the boat" in several mite lineages.

PMID- 12208819
TI  - Selective toxicity of neonicotinoids attributable to specificity of insect and
      mammalian nicotinic receptors.
AB  - Neonicotinoids, the most important new class of synthetic insecticides of the
      past three decades, are used to control sucking insects both on plants and on
      companion animals. Imidacloprid (the principal example), nitenpyram, acetamiprid,
      thiacloprid, thiamethoxam, and others act as agonists at the insect nicotinic
      acetylcholine receptor (nAChR). The botanical insecticide nicotine acts at the
      same target without the neonicotinoid level of effectiveness or safety.
      Fundamental differences between the nAChRs of insects and mammals confer
      remarkable selectivity for the neonicotinoids. Whereas ionized nicotine binds at
      an anionic subsite in the mammalian nAChR, the negatively tipped ("magic" nitro
      or cyano) neonicotinoids interact with a proposed unique subsite consisting of
      cationic amino acid residue(s) in the insect nAChR. Knowledge reviewed here of
      the functional architecture and molecular aspects of the insect and mammalian
      nAChRs and their neonicotinoid-binding site lays the foundation for continued
      development and use of this new class of safe and effective insecticides.

PMID- 12208823
TI  - The challenges of providing behavioral treatment to Asian Americans.

PMID- 12208824
TI  - The poor mental health care of Asian Americans.

PMID- 12208825
TI  - Mental health services research in Asian Americans.

PMID- 12208826
TI  - Cultural factors influencing the mental health of Asian Americans.

PMID- 12208827
TI  - Initial behavioral health assessment of Asian Americans. Part 1. Key principles.

PMID- 12208828
TI  - Part 2. Putting principles into practice.

PMID- 12208829
TI  - Depressive disorders in Asian American adults.

PMID- 12208830
TI  - Depression in Asian American children.

PMID- 12208832
TI  - Somatoform disorders.

PMID- 12208831
TI  - Anxiety disorders.

PMID- 12208833
TI  - Why is neurasthenia important in Asian cultures?

PMID- 12208834
TI  - Alcohol and substance abuse.

PMID- 12208835
TI  - Psychosis.

PMID- 12208836
TI  - Recognizing dementia.

PMID- 12208837
TI  - Prescribing medication for Asians with mental disorders.

PMID- 12208838
TI  - Chinese herbal medicines.

PMID- 12208839
TI  - Non-variceal upper gastrointestinal haemorrhage: guidelines.

PMID- 12208840
TI  - Genome instability and Rad50(S): subtle yet severe.

PMID- 12208841
TI  - The anaphase-promoting complex: it's not just for mitosis any more.

PMID- 12208842
TI  - Dysregulation of protein modification by ISG15 results in brain cell injury.
AB  - UBP43 (USP18) is a protease that removes the ubiquitin-like modifier ISG15 from
      conjugated proteins. Here we present the first report of dysregulation of protein
      ISG15 modification by the generation of UBP43 knockout mice. In the absence of
      UBP43, brain tissue showed an elevated level of ISG15 conjugates, and cellular
      necrosis was evident in the ependyma. Such disruption of the blood-brain barrier
      resulted in severe neurologic disorders. These results demonstrate that UBP43
      plays a critical role in maintaining the homeostatic balance of ISG15-conjugated
      protein, and that regulation of cellular levels of ISG15 protein modification is
      essential for brain cell function.

PMID- 12208843
TI  - Shoot meristem maintenance is controlled by a GRAS-gene mediated signal from
      differentiating cells.
AB  - Plant shoot development depends on the perpetuation of a group of
      undifferentiated cells in the shoot apical meristem (SAM). In the Petunia mutant
      hairy meristem (ham), shoot meristems differentiate postembryonically as
      continuations of the subtending stem. HAM encodes a putative transcription factor
      of the GRAS family, which acts non-cell-autonomously from L3-derived tissue of
      lateral organ primordia and stem provasculature. HAM acts in parallel with
      TERMINATOR (PhWUSCHEL) and is required for continued cellular response to
      TERMINATOR and SHOOTMERISTEMLESS (PhSTM). This reveals a novel mechanism by which
      signals from differentiating tissues extrinsically control stem cell fate in the
      shoot apex.

PMID- 12208844
TI  - Dynamic changes in histone H3 Lys 9 methylation occurring at tightly regulated
      inducible inflammatory genes.
AB  - Methylation of histone H3 at Lys 9 is causally linked to formation of
      heterochromatin and to long-term transcriptional repression. We report an
      unexpected pattern of H3 Lys 9 methylation occurring at a subset of inducible
      inflammatory genes. This pattern is characterized by relatively low constitutive
      levels of H3 Lys 9 methylation that are erased upon activation and restored
      concurrently with post-induction transcriptional repression. Changes in H3 Lys 9
      methylation strongly correlate with RNA polymerase II recruitment and release. In
      particular, remethylation correlates with RNApolII release more strongly than
      does histone deacetylation. We propose that, by generating a window of time in
      which transcription is permitted, dynamic modulation of H3 Lys 9 methylation adds
      an additional regulatory level to transcriptional activation of tightly
      controlled inducible genes.

PMID- 12208845
TI  - Mitotic-specific methylation of histone H4 Lys 20 follows increased PR-Set7
      expression and its localization to mitotic chromosomes.
AB  - We describe distinct patterns of histone methylation during human cell cycle
      progression. Histone H4 methyltransferase activity was found to be cell cycle
      regulated, consistent with increased H4 Lys 20 methylation at mitosis. This
      increase closely followed the cell cycle-regulated expression of the H4 Lys 20
      methyltransferase, PR-Set7. Localization of PR-Set7 to mitotic chromosomes and
      subsequent increase in H4 Lys 20 methylation were inversely correlated to
      transient H4 Lys 16 acetylation in early S-phase. These data suggest that H4 Lys
      20 methylation by PR-Set7 during mitosis acts to antagonize H4 Lys 16 acetylation
      and to establish a mechanism by which this mark is epigenetically transmitted.

PMID- 12208846
TI  - Evidence that Swi/Snf directly represses transcription in S. cerevisiae.
AB  - Many studies have established that the Swi/Snf family of chromatin-remodeling
      complexes activate transcription. Recent reports have suggested the possibility
      that these complexes can also repress transcription. We now present chromatin
      immunoprecipitation evidence that the Swi/Snf complex of Saccharomyces cerevisiae
      directly represses transcription of the SER3 gene. Consistent with its role in
      nucleosome remodeling, Swi/Snf controls the chromatin structure of the SER3
      promoter. However, in striking contrast to activation by Swi/Snf, which requires
      most Swi/Snf subunits, repression by Swi/Snf at SER3 is dependent primarily on
      one Swi/Snf component, Snf2. These results show distinct differences in the
      requirements for Swi/Snf components in transcriptional activation and repression.

PMID- 12208847
TI  - Cancer predisposition and hematopoietic failure in Rad50(S/S) mice.
AB  - Mre11, Rad50, and Nbs1 function in a protein complex that is central to the
      metabolism of chromosome breaks. Null mutants of each are inviable. We
      demonstrate here that hypomorphic Rad50 mutant mice (Rad50(S/S) mice) exhibited
      growth defects and cancer predisposition. Rad50(S/S) mice died with complete bone
      marrow depletion as a result of progressive hematopoietic stem cell failure.
      Similar attrition occurred in spermatogenic cells. In both contexts, attrition
      was substantially mitigated by p53 deficiency, whereas the tumor latency of p53(
      /-) and p53(+/-) animals was reduced by Rad50(S/S). Indices of genotoxic stress
      and chromosomal rearrangements were evident in Rad50(S/S) cultured cells, as well
      as in Rad50(S/S) and p53(-/-) Rad50(S/S) lymphomas, suggesting that the
      Rad50(S/S) phenotype was attributable to chromosomal instability. These outcomes
      were not associated with overt defects in the Mre11 complex's previously
      established double strand break repair and cell cycle checkpoint regulation
      functions. The data indicate that even subtle perturbation of Mre11 complex
      functions results in severe genotoxic stress, and that the complex is critically
      important for homeostasis of proliferative tissues.

PMID- 12208848
TI  - Specific down-modulation of Notch1 signaling in cervical cancer cells is required
      for sustained HPV-E6/E7 expression and late steps of malignant transformation.
AB  - The Notch family of cell surface receptors plays a key role in cell-fate
      determination and differentiation, functioning in a cell- and context-specific
      manner. In mammalian cells, Notch activation is generally thought to maintain
      stem cell potential and inhibit differentiation, thereby promoting
      carcinogenesis. However, in other contexts such as primary epithelial cells
      (keratinocytes), increased Notch activity causes exit from the cell cycle and/or
      commitment to differentiation. We now report that expression of the endogenous
      Notch1 gene is markedly reduced in a panel of cervical carcinoma cells whereas
      expression of Notch2 remains elevated, and Notch1 expression is similarly reduced
      or absent in invasive cervical cancers. Conversely, expression of activated
      Notch1 causes strong growth inhibition of HPV-positive, but not HPV-negative,
      cervical carcinoma cells, but exerts no such effects on other epithelial tumor
      cells. Increased Notch1 signaling, but not Notch2, causes a dramatic down
      modulation of HPV-driven transcription of the E6/E7 viral genes, through
      suppression of AP-1 activity by up-regulation of the Fra-1 family member and
      decreased c-Fos expression. Thus, Notch1 exerts specific protective effects
      against HPV-induced transformation through suppression of E6/E7 expression, and
      down-modulation of Notch1 expression is likely to play an important role in late
      stages of HPV-induced carcinogenesis.

PMID- 12208849
TI  - Disruption of the gene encoding the latent transforming growth factor-beta
      binding protein 4 (LTBP-4) causes abnormal lung development, cardiomyopathy, and
      colorectal cancer.
AB  - Transforming growth factor-betas (TGF-betas) are multifunctional growth factors
      that are secreted as inactive (latent) precursors in large protein complexes.
      These complexes include the latency-associated propeptide (LAP) and a latent
      transforming growth factor-beta binding protein (LTBP). Four isoforms of LTBPs
      (LTBP-1-LTBP-4) have been cloned and are believed to be structural components of
      connective tissue microfibrils and local regulators of TGF-beta tissue deposition
      and signaling. By using a gene trap strategy that selects for integrations into
      genes induced transiently during early mouse development, we have disrupted the
      mouse homolog of the human LTBP-4 gene. Mice homozygous for the disrupted allele
      develop severe pulmonary emphysema, cardiomyopathy, and colorectal cancer. These
      highly tissue-specific abnormalities are associated with profound defects in the
      elastic fiber structure and with a reduced deposition of TGF-beta in the
      extracellular space. As a consequence, epithelial cells have reduced levels of
      phosphorylated Smad2 proteins, overexpress c-myc, and undergo uncontrolled
      proliferation. This phenotype supports the predicted dual role of LTBP-4 as a
      structural component of the extracellular matrix and as a local regulator of TGF
      beta tissue deposition and signaling.

PMID- 12208850
TI  - Identification of a new APC/C recognition domain, the A box, which is required
      for the Cdh1-dependent destruction of the kinase Aurora-A during mitotic exit.
AB  - The mitotic kinase Aurora A (Aur-A) is required for formation of a bipolar
      mitotic spindle and accurate chromosome segregation. In somatic cells, Aur-A
      protein and kinase activity levels peak during mitosis, and Aur-A is degraded
      during mitotic exit. Here, we investigated how Aur-A protein and kinase activity
      levels are regulated, taking advantage of the rapid synchronous cell division
      cycles of Xenopus eggs and cell-free systems derived from them. Aur-A kinase
      activity oscillates in the early embryonic cell cycles, just as in somatic cells,
      but Aur-A protein levels are constant, indicating that regulated activation and
      inactivation, instead of periodic proteolysis, is the dominant mode of Aur-A
      regulation in these cell cycles. Cdh1, the APC/C activator that targets many
      mitotic proteins for ubiquitin-dependent proteolysis during late mitosis and G1
      in somatic cells, is missing in Xenopus eggs and early embryos. We find that
      addition of Cdh1 to egg extracts undergoing M phase exit is sufficient to induce
      rapid degradation of Aur-A. Aur-A contains both of the two known APC/C
      recognition signals, (1) a C-terminal D box similar to those required for
      ubiquitin-dependent destruction of cyclin B and several other mitotic proteins,
      and (2) an N-terminal KEN box similar to that found on cdc20, which is
      ubiquitinated in response to APC/C(Cdh1). The D box is required for Cdh1-induced
      destruction of Aur-A but the KEN box is not. Destruction also requires a short
      region in the N terminus, which contains a newly identified recognition signal,
      the A box. The A box is conserved in vertebrate Aur-As and contains serine 53,
      which is phosphorylated during M phase. Mutation of serine 53 to aspartic acid,
      which can mimic the effect of phosphorylation, completely blocks Cdh1-dependent
      destruction of Aur-A. These results suggest that dephosphorylation of serine 53
      during mitotic exit could control the timing of Aur-A destruction, allowing
      recognition of both the A box and D box by Cdh1-activated APC/C.

PMID- 12208851
TI  - Interactions between Ras1, dMyc, and dPI3K signaling in the developing Drosophila
      wing.
AB  - The Ras GTPase links extracellular signals to intracellular mechanisms that
      control cell growth, the cell cycle, and cell identity. An activated form of
      Drosophila Ras (Ras(V12)) promotes these processes in the developing wing, but
      the effector pathways involved are unclear. Here, we present evidence indicating
      that Ras(V12) promotes cell growth and G(1)/S progression by increasing dMyc
      protein levels and activating dPI3K signaling, and that it does so via separate
      effector pathways. We also show that endogenous Ras is required to maintain
      normal levels of dMyc, but not dPI3K signaling during wing development. Finally,
      we show that induction of dMyc and regulation of cell identity are separable
      effects of Raf/MAPK signaling. These results suggest that Ras may only affect
      PI3K signaling when mutationally activated, such as in Ras(V12)-transformed
      cells, and provide a basis for understanding the synergy between Ras and other
      growth-promoting oncogenes in cancer.

PMID- 12208852
TI  - RNA chaperone StpA loosens interactions of the tertiary structure in the td group
      I intron in vivo.
AB  - Efficient splicing of the td group I intron in vivo is dependent on the ribosome.
      In the absence of translation, the pre-mRNA is trapped in nonnative-splicing
      incompetent conformations. Alternatively, folding of the pre-mRNA can be promoted
      by the RNA chaperone StpA or by the group I intron-specific splicing factor Cyt
      18. To understand the mechanism of action of RNA chaperones, we probed the impact
      of StpA on the structure of the td intron in vivo. Our data suggest that StpA
      loosens tertiary interactions. The most prominent structural change was the
      opening of the base triples, which are involved in the correct orientation of the
      two major intron core domains. In line with the destabilizing activity of StpA,
      splicing of mutant introns with a reduced structural stability is sensitive to
      StpA. In contrast, Cyt-18 strengthens tertiary contacts, thereby rescuing
      splicing of structurally compromised td mutants in vivo. Our data provide direct
      evidence for protein-induced conformational changes within catalytic RNA in vivo.
      Whereas StpA resolves tertiary contacts enabling the RNA to refold, Cyt-18
      contributes to the overall compactness of the td intron in vivo.

PMID- 12208853
TI  - Biological evidence that SOCS-2 can act either as an enhancer or suppressor of
      growth hormone signaling.
AB  - Suppressor of cytokine signaling (SOCS)-2 is a member of a family of
      intracellular proteins implicated in the negative regulation of cytokine
      signaling. The generation of SOCS-2-deficient mice, which grow to one and a half
      times the size of their wild-type littermates, suggests that SOCS-2 may attenuate
      growth hormone (GH) signaling. In vitro studies indicate that, while SOCS-2 can
      inhibit GH action at low concentrations, at higher concentrations it may
      potentiate signaling. To determine whether a similar enhancement of signaling is
      observed in vivo or alternatively whether increased SOCS-2 levels repress growth
      in vivo, we generated and analyzed transgenic mice that overexpress SOCS-2 from a
      human ubiquitin C promoter. These mice are not growth-deficient and are, in fact,
      significantly larger than wild-type mice. The overexpressed SOCS-2 was found to
      bind to endogenous GH receptors in a number of mouse organs, while phosphopeptide
      binding studies with recombinant SOCS-2 defined phosphorylated tyrosine 595 on
      the GH receptor as the site of interaction. Together, the data implicate SOCS-2
      as having dual effects on GH signaling in vivo.

PMID- 12208854
TI  - Granulocyte/macrophage-colony-stimulating factor (GM-CSF) regulates lung innate
      immunity to lipopolysaccharide through Akt/Erk activation of NFkappa B and AP-1
      in vivo.
AB  - The lung innate immune response to lipopolysaccharide (LPS) coordinates cellular
      inflammation, mediator, and protease release essential for host defense but
      deleterious in asthma, chronic obstructive pulmonary disease, and cystic
      fibrosis. In vitro, LPS signals to the transcription factors NFkappaB via TLR4,
      MyD88, and IL-1R-associated kinase (IRAK), to AP-1 by mitogen-activated protein
      (MAP) kinases, and via an alternate route in IRAK-deficient mice, but the in vivo
      lung signaling pathway(s) are not understood. We investigated the role of Akt and
      Erk1/2 as LPS intensely stimulates granulocyte/macrophage-colony-stimulating
      factor (GM-CSF) release, and neutralizing GM-CSF profoundly suppressed LPS
      induced inflammation, suppressed expression and activity of lung proteases,
      significantly reduced GM-CSF and tumor necrosis factor alpha (TNFalpha) mRNA
      expression, and dampened nuclear localization of both NFkappaB (p50/65) and AP-1.
      LPS markedly activated Akt and Erk1/2, but not p38, in a GM-CSF-dependent manner
      in direct temporal association with NFkappaB and AP-1 activation. Pharmacological
      inhibition of Akt or Erk activation in LPS-treated tracheal explants ex vivo
      inhibited the release of GM-CSF. These data implicate GM-CSF-dependent activation
      of Akt in the amplification of this response and demonstrate the role of Erks
      rather than p38 in lung LPS inflammatory responses. Inhibition of GM-CSF may be
      of therapeutic benefit in inflammatory diseases in which LPS contributes to lung
      damage.

PMID- 12208855
TI  - An increasingly complex code.

PMID- 12208856
TI  - Cholesterol in health and disease.

PMID- 12208857
TI  - Cholesterol modification of Hedgehog family proteins.

PMID- 12208858
TI  - Cholesterol, lipid rafts, and disease.

PMID- 12208859
TI  - Biliary cholesterol secretion by the twinned sterol half-transporters ABCG5 and
      ABCG8.

PMID- 12208860
TI  - Targeting rheumatoid inflammation and joint destruction in the mouse.

PMID- 12208861
TI  - A confederacy of proteinases.

PMID- 12208862
TI  - Androgen receptor-mediated inhibition of cutaneous wound healing.
AB  - Impaired wound healing states in the elderly lead to substantial morbidity,
      mortality, and a cost to the US Health Services of over $9 billion per annum. In
      addition to intrinsic aging per se causing delayed healing, studies have
      suggested marked sex-differences in wound repair. We report that castration of
      male mice results in a striking acceleration of local cutaneous wound healing,
      and is associated with a reduced inflammatory response and increased hair growth.
      Using a hairless mouse model, we have demonstrated that testosterone reduction
      stimulates the healing response not through hair follicle epithelial/mesenchymal
      cell proliferation, but directly via effects on wound cell populations. We
      suggest that endogenous testosterone inhibits the cutaneous wound healing
      response in males and is associated with an enhanced inflammatory response. The
      mechanisms underlying the observed effects involve a direct upregulation of
      proinflammatory cytokine expression by macrophages in response to testosterone.
      Blockade of androgen action systemically, via receptor antagonism, accelerates
      healing significantly, suggesting a specific target for future therapeutic
      intervention in impaired wound healing states in elderly males.

PMID- 12208863
TI  - Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms.
AB  - Matrix metalloproteinases (MMPs) 9 and 2 are increased in human abdominal aortic
      aneurysm (AAA) tissue, but their precise role and potential interaction remain
      unclear. Experimental induction of aortic aneurysms in mice genetically deficient
      in these peptidases could provide new insight into AAA pathogenesis. Mice
      deficient in the expression of MMP-9 (MMP-9KO) or MMP-2 (MMP-2KO) and their
      corresponding wild-type background mice (WT) underwent AAA induction by abluminal
      application of calcium chloride (CaCl(2)). No aneurysm formation was observed at
      10 weeks after treatment in either the MMP-9KO or the MMP-2KO mice, whereas the
      corresponding WT mice showed an average 74% and 52% increase in aortic diameter,
      respectively. Reinfusion of competent macrophages from the corresponding WT
      strains into knockout mice resulted in reconstitution of AAA in MMP-9KO but not
      MMP-2KO mice. These findings suggest that macrophage-derived MMP-9 and
      mesenchymal cell MMP-2 are both required and work in concert to produce AAA.

PMID- 12208864
TI  - Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer.
AB  - Estrogen receptor (ER) expression and Her-2 amplification define specific subsets
      of breast tumors for which specific therapies exist. The S-phase kinase
      associated protein Skp2 is required for the ubiquitin-mediated degradation of the
      cdk-inhibitor p27 and is a bona fide proto-oncoprotein. Using microarray analysis
      and immunohistochemistry, we determined that higher levels of Skp2 are present
      more frequently in ER-negative tumors than in ER-positive cases. Interestingly,
      the subset of ER-negative breast carcinomas overexpressing Skp2 are also
      characterized by high tumor grade, negativity for Her-2, basal-like phenotype,
      high expression of certain cell cycle regulatory genes, and low levels of p27
      protein. We also found that Skp2 expression is cell adhesion-dependent in normal
      human mammary epithelial cells but not in breast cancer cells and that an
      inhibition of Skp2 induces a decrease of adhesion-independent growth in both ER
      positive and ER-negative cancer cells. Finally, forced expression of Skp2
      abolished effects of antiestrogens, suggesting that deregulated Skp2 expression
      might play a role in the development of resistance to antiestrogens. We conclude
      that Skp2 has oncogenic potential in breast epithelial cells and is overexpressed
      in a subset of breast carcinomas (ER- and Her-2 negative) for which Skp2
      inhibitors may represent a valid therapeutic option.

PMID- 12208865
TI  - An ATF2-derived peptide sensitizes melanomas to apoptosis and inhibits their
      growth and metastasis.
AB  - Melanomas are among the aggressive tumor types because of their notorious
      resistance to treatment and their high capacity to metastasize. ATF2 is among
      transcription factors implicated in the progression of melanoma and its
      resistance to treatment. Here we demonstrate that the expression of a peptide
      spanning amino acids 50-100 of ATF2 (ATF2(50-100)) reduces ATF2 transcriptional
      activities while increasing the expression and activity of c-Jun. Altering the
      balance of Jun/ATF2 transcriptional activities sensitized melanoma cells to
      apoptosis, an effect that could be attenuated by inhibiting c-Jun. Inhibition of
      ATF2 via RNA interference likewise increased c-Jun expression and primed melanoma
      cells to undergo apoptosis. Growth and metastasis of SW1 and B16F10 mouse
      melanomas were inhibited by ATF2(50-100) to varying degrees up to a complete
      regression, depending on the mode (inducible, constitutive, or adenoviral
      delivery) of its expression.

PMID- 12208866
TI  - The role of prostaglandin E2 receptors in the pathogenesis of rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disorder leading to bone and
      cartilage destruction. A substantial body of evidence suggests that prostaglandin
      E2 (PGE2) contributes to the pathogenesis of RA, and nonsteroidal anti
      inflammatory drugs, inhibitors of the synthesis of PGE2 and other prostanoids,
      continue to be used in the treatment of this disease. To begin to understand the
      mechanism by which prostaglandins modulate the pathophysiology of this disease,
      we examined mice lacking each of the four known PGE2 (EP) receptors after
      generation of collagen antibody-induced arthritis, an animal model of RA.
      Homozygous deletion of the EP1, EP2, or EP3 receptors did not affect the
      development of arthritis, whereas EP4 receptor-deficient mice showed decreased
      incidence and severity of disease. These animals also showed reduced inflammation
      as assessed by circulating IL-6 and serum amyloid A levels. Joint histopathology
      of EP4(-/-) animals revealed reduced bone destruction, proteoglycan loss, and
      type II collagen breakdown in cartilage compared with EP4(+/+) mice. Furthermore,
      liver and macrophages isolated from EP4(-/-) animals produced significantly less
      IL-1 beta and IL-6 than control samples. Thus, PGE2 contributes to disease
      progression at least in part by binding to the EP4 receptor. Antagonists of this
      receptor might therefore provide novel agents for the treatment of RA.

PMID- 12208867
TI  - Coexpression of ATP-binding cassette proteins ABCG5 and ABCG8 permits their
      transport to the apical surface.
AB  - Mutations in either ATP-binding cassette (ABC) G5 or ABCG8 cause sitosterolemia,
      an autosomal recessive disorder of sterol trafficking. To determine the site of
      action of ABCG5 and ABCG8, we expressed recombinant, epitope-tagged mouse ABCG5
      and ABCG8 in cultured cells. Both ABCG5 and ABCG8 underwent N-linked
      glycosylation. When either protein was expressed individually in cells, the N
      linked sugars remained sensitive to Endoglycosidase H (Endo H). When ABCG5 and
      ABCG8 were coexpressed, the attached sugars were Endo H-resistant and
      neuraminidase-sensitive, indicating that the proteins were transported to the
      trans-Golgi complex. The mature, glycosylated forms of ABCG5 and ABCG8
      coimmunoprecipitated, consistent with heterodimerization of these two proteins.
      The Endo H-sensitive forms of ABCG5 and ABCG8 were confined to the endoplasmic
      reticulum (ER), whereas the mature forms were present in non-ER fractions in
      cultured hepatocytes. Immunoelectron microscopy revealed ABCG5 and ABCG8 on the
      plasma membrane of these cells. In polarized WIF-B cells, recombinant ABCG5
      localized to the apical (canalicular) membrane when coexpressed with ABCG8, but
      not when expressed alone. To our knowledge this is the first direct demonstration
      that trafficking of an ABC half-transporter to the cell surface requires the
      presence of its dimerization partner.

PMID- 12208868
TI  - Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and
      reduces fractional absorption of dietary cholesterol.
AB  - Two ATP-binding cassette (ABC) transporters, ABCG5 and ABCG8, have been proposed
      to limit sterol absorption and to promote biliary sterol excretion in humans. To
      test this hypothesis, a P1 clone containing the human ABCG5 and ABCG8 genes was
      used to generate transgenic mice. The transgenes were expressed primarily in the
      liver and small intestine, mirroring the expression pattern of the endogenous
      genes. Transgene expression only modestly affected plasma and liver cholesterol
      levels but profoundly altered cholesterol transport. The fractional absorption of
      dietary cholesterol was reduced by about 50%, and biliary cholesterol levels were
      increased more than fivefold. Fecal neutral sterol excretion was increased three-
      to sixfold and hepatic cholesterol synthesis increased two- to fourfold in the
      transgenic mice. No significant changes in the pool size, composition, and fecal
      excretion of bile acids were observed in the transgenic mice. Transgene
      expression attenuated the increase in hepatic cholesterol content induced by
      consumption of a high cholesterol diet. These results demonstrate that increased
      expression of ABCG5 and ABCG8 selectively drives biliary neutral sterol secretion
      and reduces intestinal cholesterol absorption, leading to a selective increase in
      neutral sterol excretion and a compensatory increase in cholesterol synthesis.

PMID- 12208869
TI  - Vitamin E inhibits CD95 ligand expression and protects T cells from activation
      induced cell death.
AB  - Apoptosis is a morphologically distinct form of cell death involved in many
      physiological and pathological processes. Expression of the CD95 (APO-1/Fas)
      ligand (CD95L) is critically involved in activation-induced cell death (AICD) of
      activated T cells. Here we show that the natural free radical scavenger vitamin E
      suppresses the activity of the transcription factors NF-kappa B and AP-1, thus
      blocking expression of CD95L and preventing T cell AICD. Since AICD is a major
      cause of T cell depletion in AIDS, we examined 35 HIV-1-positive individuals and
      found that their T cells are more susceptible to AICD than are T cells isolated
      from healthy controls. Administration of vitamin E suppresses CD95L mRNA
      expression and protects T cells of HIV-1-infected individuals from CD95-mediated
      apoptosis. This evidence that vitamin E can affect T cell survival may merit
      further clinical investigation.

PMID- 12208870
TI  - Different mechanisms underlying the stimulation of K(Ca) channels by nitric oxide
      and carbon monoxide.
AB  - The molecular mechanisms underlying the effects of nitric oxide (NO) and carbon
      monoxide (CO), individually and collectively, on large-conductance calcium
      activated K(+) (K(Ca)) channels were investigated in rat vascular smooth muscle
      cells (SMCs). Both NO and CO increased the activity of native K(Ca) channels.
      Dehydrosoyasaponin-I, a specific agonist for beta subunit of K(Ca) channels,
      increased the open probability of native K(Ca) channels only when it was
      delivered to the cytoplasmic surface of membrane. CO, but not NO, further
      increased the activity of native K(Ca) channels that had been maximally
      stimulated by dehydrosoyasaponin-I. After treatment of SMCs with anti-K(Ca),beta
      subunit antisense oligodeoxynucleotides, the stimulatory effect of NO, but not of
      CO, on K(Ca) channels was nullified. CO, but not NO, enhanced the K(Ca) current
      densities of heterologously expressed cloned K(Ca),alpha subunit, showing that
      the presence of K(Ca),beta subunit is not a necessity for the effect of CO but
      essential for that of NO. Finally, pretreatment of SMCs with NO abolished the
      effects of subsequently applied CO or diethyl pyrocarbonate on K(Ca) channels. In
      summary, the stimulatory effects of CO and NO on K(Ca) channels rely on the
      specific interactions of these gases with K(Ca),alpha and K(Ca),beta subunits.

PMID- 12208871
TI  - Tr1 cell-dependent active tolerance blunts the pathogenic effects of determinant
      spreading.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune
      disease of the CNS. The current study shows that even in an acute episode of
      disease the autoimmune response spreads from one determinant on myelin basic
      protein (MBP) to the other linked determinant and that this spread plays a
      functional role in the pathogenesis of disease. The soluble form of each
      determinant could be used to induce Ag-specific T cell tolerance and reverse an
      ongoing disease. We show that the rapid effect of soluble peptide therapy is due
      to repolarization of autoimmune T cells undergoing activation. We suggest that at
      least two different types of regulatory T cells participate in the induction of
      active tolerance. The first, yet to be fully characterized, functions in an IL-4
      dependent manner. The second produces high levels of IL-10 and low levels of IL-4
      (Tr1). We bring about completing evidence showing that these Tr1 cells play a
      pivotal role in the regulation of T cell tolerance during determinant spread and
      that soluble peptide therapy with the determinant to which the autoimmune
      response spreads amplifies a de novo regulatory mechanism aimed to reduce the
      pathological consequences of determinant spreading.

PMID- 12208872
TI  - New mechanisms for vascular control of inflammation mediated by natural
      anticoagulant proteins.

PMID- 12208873
TI  - The lectin-like domain of thrombomodulin confers protection from neutrophil
      mediated tissue damage by suppressing adhesion molecule expression via nuclear
      factor kappaB and mitogen-activated protein kinase pathways.
AB  - Thrombomodulin (TM) is a vascular endothelial cell (EC) receptor that is a
      cofactor for thrombin-mediated activation of the anticoagulant protein C. The
      extracellular NH(2)-terminal domain of TM has homology to C-type lectins that are
      involved in immune regulation. Using transgenic mice that lack this structure
      (TM(LeD/LeD)), we show that the lectin-like domain of TM interferes with
      polymorphonuclear leukocyte (PMN) adhesion to ECs by intercellular adhesion
      molecule 1-dependent and -independent pathways through the suppression of
      extracellular signal-regulated kinase (ERK)(1/2) activation. TM(LeD/LeD) mice
      have reduced survival after endotoxin exposure, accumulate more PMNs in their
      lungs, and develop larger infarcts after myocardial ischemia/reperfusion. The
      recombinant lectin-like domain of TM suppresses PMN adhesion to ECs, diminishes
      cytokine-induced increase in nuclear factor kappaB and activation of ERK(1/2),
      and rescues ECs from serum starvation, findings that may explain why plasma
      levels of soluble TM are inversely correlated with cardiovascular disease. These
      data suggest that TM has antiinflammatory properties in addition to its role in
      coagulation and fibrinolysis.

PMID- 12208874
TI  - Long-lived memory T lymphocyte responses after hantavirus infection.
AB  - Puumala virus (PUUV) is a hantavirus that causes hemorrhagic fever with renal
      syndrome (HFRS), which is an important public health problem in large parts of
      Europe. We examined the memory cytolytic T lymphocyte (CTL) responses in 13
      Finnish individuals who had HFRS between 1984 and 1995. In seven of these donors,
      we detected virus-specific CTL responses against the PUUV nucleocapsid (N)
      protein after in vitro stimulation with PUUV. Six novel CD8(+) CTL epitopes were
      defined on the N protein and were found to be restricted by various HLA alleles
      including A2, A28, B7, and B8. This is the first demonstration of PUUV-specific
      CTL responses in humans, and the first identification of CTL epitopes on PUUV. In
      addition, this study provides one of the few characterizations of a human
      antiviral memory T cell response, without the complicating issues of virus
      persistence or reinfection. Interferon (IFN)-gamma ELISPOT analysis showed that
      memory CTL specific for these epitopes were present at high frequency in PUUV
      immune individuals many years after acute infection in the absence of detectable
      viral RNA. The frequencies of PUUV-specific CTL were comparable to or exceeded
      those found in other viral systems including influenza, EBV and HIV, in which CTL
      responses may be boosted by periodic reinfection or virus persistence.

PMID- 12208875
TI  - Constitutive activation of the SRC family kinase Hck results in spontaneous
      pulmonary inflammation and an enhanced innate immune response.
AB  - To identify the physiological role of Hck, a functionally redundant member of the
      Src family of tyrosine kinases expressed in myelomonocytic cells, we generated
      Hck(F/F) "knock-in" mice which carry a targeted tyrosine (Y) to phenylalanine (F)
      substitution of the COOH-terminal, negative regulatory Y(499)-residue in the Hck
      protein. Unlike their Hck(-/-) "loss-of-function" counterparts, Hck(F/F) "gain-of
      function" mice spontaneously acquired a lung pathology characterized by extensive
      eosinophilic and mononuclear cell infiltration within the lung parenchyma,
      alveolar airspaces, and around blood vessels, as well as marked epithelial mucus
      metaplasia in conducting airways. Lungs from Hck(F/F) mice showed areas of mild
      emphysema and pulmonary fibrosis, which together with inflammation resulted in
      altered lung function and respiratory distress in aging mice. When challenged
      transnasally with lipopolysaccharide (LPS), Hck(F/F) mice displayed an
      exaggerated pulmonary innate immune response, characterized by excessive release
      of matrix metalloproteinases and tumor necrosis factor (TNF)alpha. Similarly,
      Hck(F/F) mice were highly sensitive to endotoxemia after systemic administration
      of LPS, and macrophages and neutrophils derived from Hck(F/F) mice exhibited
      enhanced effector functions in vitro (e.g., nitric oxide and TNFalpha production,
      chemotaxis, and degranulation). Based on the demonstrated functional association
      of Hck with leukocyte integrins, we propose that constitutive activation of Hck
      may mimic adhesion-dependent priming of leukocytes. Thus, our observations
      collectively suggest an enhanced innate immune response in Hck(F/F) mice thereby
      skewing innate immunity from a reversible physiological host defense response to
      one causing irreversible tissue damage.

PMID- 12208876
TI  - Nuclear factor kappaB-dependent gene expression profiling of Hodgkin's disease
      tumor cells, pathogenetic significance, and link to constitutive signal
      transducer and activator of transcription 5a activity.
AB  - Constitutive nuclear nuclear factor (NF)-kappaB activity is observed in a variety
      of hematopoietic and solid tumors. Given the distinctive role of constitutive NF
      kappaB for Hodgkin and Reed-Sternberg (HRS) cell viability, we performed
      molecular profiling in two Hodgkin's disease (HD) cell lines to identify NF
      kappaB target genes. We recognized 45 genes whose expression in both cell lines
      was regulated by NF-kappaB. The NF-kappaB-dependent gene profile comprises
      chemokines, cytokines, receptors, apoptotic regulators, intracellular signaling
      molecules, and transcription factors, the majority of which maintain a marker
      like expression in HRS cells. Remarkably, we found 17 novel NF-kappaB target
      genes. Using chromatin immunoprecipitation we demonstrate that NF-kappaB is
      recruited directly to the promoters of several target genes, including signal
      transducer and activator of transcription (STAT)5a, interleukin-13, and CC
      chemokine receptor 7. Intriguingly, NF-kappaB positively regulates STAT5a
      expression and signaling pathways in HRS cells, and promotes its persistent
      activation. In fact, STAT5a overexpression was found in most tumor cells of
      tested patients with classical HD, indicating a critical role for HD. The gene
      profile underscores a central role of NF-kappaB in the pathogenesis of HD and
      potentially of other tumors with constitutive NF-kappaB activation.

PMID- 12208877
TI  - Disease-associated bias in T helper type 1 (Th1)/Th2 CD4(+) T cell responses
      against MAGE-6 in HLA-DRB10401(+) patients with renal cell carcinoma or melanoma.
AB  - T helper type 1 (Th1)-type CD4(+) antitumor T cell help appears critical to the
      induction and maintenance of antitumor cytotoxic T lymphocyte (CTL) responses in
      vivo. In contrast, Th2- or Th3/Tr-type CD4(+) T cell responses may subvert Th1
      type cell-mediated immunity, providing a microenvironment conducive to disease
      progression. We have recently identified helper T cell epitopes derived from the
      MAGE-6 gene product; a tumor-associated antigen expressed by most melanomas and
      renal cell carcinomas. In this study, we have assessed whether peripheral blood
      CD4(+) T cells from human histocompatibility leukocyte antigens (HLA)
      DRbeta1*0401(+) patients are Th1- or Th2-biased to MAGE-6 epitopes using
      interferon (IFN)-gamma and interleukin (IL)-5 enzyme-linked immunospot assays,
      respectively. Strikingly, the vast majority of patients with active disease were
      highly-skewed toward Th2-type responses against MAGE-6-derived epitopes,
      regardless of their stage (stage I versus IV) of disease, but retained Th1-type
      responses against Epstein-Barr virus- or influenza-derived epitopes. In marked
      contrast, normal donors and cancer patients with no current evidence of disease
      tended to exhibit either mixed Th1/Th2 or strongly Th1-polarized responses to
      MAGE-6 peptides, respectively. CD4(+) T cell secretion of IL-10 and transforming
      growth factor (TGF)-beta1 against MAGE-6 peptides was not observed, suggesting
      that specific Th3/Tr-type CD4(+) subsets were not common events in these
      patients. Our data suggest that immunotherapeutic approaches will likely have to
      overcome or complement systemic Th2-dominated, tumor-reactive CD4(+) T cell
      responses to provide optimal clinical benefit.

PMID- 12208879
TI  - Activation of STAT3 by the hepatitis C virus core protein leads to cellular
      transformation.
AB  - The signal transducer and activator of transcription (STAT) family proteins are
      transcription factors critical in mediating cytokine signaling. Among them, STAT3
      is often constitutively phosphorylated and activated in human cancers and in
      transformed cell lines and is implicated in tumorigenesis. However, cause of the
      persistent activation of STAT3 in human tumor cells is largely unknown. The
      hepatitis C virus (HCV) is a major etiological agent of non-A and non-B
      hepatitis, and chronic infection by HCV is associated with development of liver
      cirrhosis and hepatocellular carcinoma. HCV core protein is proposed to be
      responsible for the virus-induced transformation. We now report that HCV core
      protein directly interacts with and activates STAT3 through phosphorylation of
      the critical tyrosine residue. Activation of STAT3 by the HCV core in NIH-3T3
      cells resulted in rapid proliferation and up-regulation of Bcl-XL and cyclin-D1.
      Additional expression of STAT3 in HCV core-expressing cells resulted in anchorage
      independent growth and tumorigenesis. We propose that the HCV core protein
      cooperates with STAT3, which leads to cellular transformation.

PMID- 12208878
TI  - Chronic lymphocytic leukemia B cells can undergo somatic hypermutation and
      intraclonal immunoglobulin V(H)DJ(H) gene diversification.
AB  - Chronic lymphocytic leukemia (CLL) arises from the clonal expansion of a CD5(+) B
      lymphocyte that is thought not to undergo intraclonal diversification. Using
      V(H)DJ(H) cDNA single strand conformation polymorphism analyses, we detected
      intraclonal mobility variants in 11 of 18 CLL cases. cDNA sequence analyses
      indicated that these variants represented unique point-mutations (1-35/patient).
      In nine cases, these mutations were unique to individual submembers of the CLL
      clone, although in two cases they occurred in a large percentage of the clonal
      submembers and genealogical trees could be identified. The diversification
      process responsible for these changes led to single nucleotide changes that
      favored transitions over transversions, but did not target A nucleotides and did
      not have the replacement/silent nucleotide change characteristics of antigen
      selected B cells. Intraclonal diversification did not correlate with the original
      mutational load of an individual CLL case in that diversification was as frequent
      in CLL cells with little or no somatic mutations as in those with considerable
      mutations. Finally, CLL B cells that did not exhibit intraclonal diversification
      in vivo could be induced to mutate their V(H)DJ(H) genes in vitro after
      stimulation. These data indicate that a somatic mutation mechanism remains
      functional in CLL cells and could play a role in the evolution of the clone.

PMID- 12208880
TI  - I-PLA(2) activation during apoptosis promotes the exposure of membrane
      lysophosphatidylcholine leading to binding by natural immunoglobulin M antibodies
      and complement activation.
AB  - Deficiency of serum immunoglobulin (Ig)M is associated with the development of a
      lupus-like disease in mice. Recent studies suggest that classical complement
      components facilitate the clearance of apoptotic cells and that failure to do so
      predisposes mice to lupus. Since IgM is a potent activator of the classical
      complement pathway, we examined IgM binding to dying cells. IgM, but not IgG,
      bound to apoptotic T cells through the Fab' portion of the antibody. Exposure of
      apoptotic cell membranes to phospholipase (PL) A2 increased, whereas PLD reduced,
      IgM binding and complement activation. Absorption studies combined with direct
      plate binding assays, revealed that IgM antibodies failed to bind to phosphatidyl
      lipids, but did recognize lysophosphatidylcholine and the phosphorylcholine head
      group. Both iPLA(2) and cPLA(2) are activated during apoptosis. Since inhibition
      of iPLA2, but not cPLA2, attenuated IgM binding to apoptotic cells, these results
      strongly suggest that the endogenous calcium independent PLA(2), iPLA(2), is
      involved in the hydrolysis of plasma membrane phospholipids and exposure of the
      epitope(s) recognized by IgM. We propose that recognition of dying cells by
      natural IgM antibodies is, in part, responsible for complement activation on
      dying cells leading to their safe clearance.

PMID- 12208881
TI  - Crosstalk between BCR/ABL oncoprotein and CXCR4 signaling through a Src family
      kinase in human leukemia cells.
AB  - Stromal-derived factor (SDF)-1 and its G protein-coupled receptor, CXCR4,
      regulate stem/progenitor cell migration and retention in the marrow and are
      required for hematopoiesis. We show here an interaction between CXCR4 and the Src
      related kinase, Lyn, in normal progenitors. We demonstrate that CXCR4-dependent
      stimulation of Lyn is associated with the activation of phosphatidylinositol 3
      kinase (PI3-kinase). This chemokine signaling, which involves a Src-related
      kinase and PI3-kinase, appears to be a target for BCR/ABL, a fusion oncoprotein
      expressed only in leukemia cells. We show that the binding of phosphorylated
      BCR/ABL to Lyn results in the constitutive activation of Lyn and PI3-kinase,
      along with a total loss of responsiveness of these kinases to SDF-1 stimulation.
      Inhibition of BCR/ABL tyrosine kinase with STI571 restores Lyn responsiveness to
      SDF-1 signaling. Thus, BCR/ABL perturbs Lyn function through a tyrosine kinase
      dependent mechanism. Accordingly, the blockade of Lyn tyrosine kinase inhibits
      both BCR/ABL-dependent and CXCR4-dependent cell movements. Our results
      demonstrate, for the first time, that Lyn-mediated pathological crosstalk exists
      between BCR/ABL and the CXCR4 pathway in leukemia cells, which disrupts chemokine
      signaling and chemotaxis, and increases the ability of immature cells to escape
      from the marrow. These results define a Src tyrosine kinases-dependent mechanism
      whereby BCR/ABL (and potentially other oncoproteins) dysregulates G protein
      coupled receptor signaling and function of mammalian precursors.

PMID- 12208882
TI  - The junctional adhesion molecule 3 (JAM-3) on human platelets is a
      counterreceptor for the leukocyte integrin Mac-1.
AB  - The recently described junctional adhesion molecules (JAMs) in man and mice are
      involved in homotypic and heterotypic intercellular interactions. Here, a third
      member of this family, human JAM-3, was identified and described as a novel
      counterreceptor on platelets for the leukocyte beta2-integrin Mac-1 (alphaMbeta2,
      CD11b/CD18). With the help of two monoclonal antibodies, Gi11 and Gi13, against a
      43-kD surface glycoprotein on human platelets, a full-length cDNA encoding JAM-3
      was identified. JAM-3 is a type I transmembrane glycoprotein containing two Ig
      like domains. Although JAM-3 did not undergo homophilic interactions, myelo
      monocytic cells adhered to immobilized JAM-3 or to JAM-3-transfected cells. This
      heterophilic interaction was specifically attributed to a direct interaction of
      JAM-3 with the beta2-integrin Mac-1 and to a lower extent with p150.95
      (alphaXbeta2, CD11c/CD18) but not with LFA-1 (alphaLbeta2, CD11a/CD18) or with
      beta1-integrins. These results were corroborated by analysis of K562
      erythroleukemic cells transfected with different heterodimeric beta2-integrins
      and by using purified proteins. Moreover, purified JAM-3 or antibodies against
      JAM-3 blocked the platelet-neutrophil interaction, indicating that platelet JAM-3
      serves as a counterreceptor for Mac-1 mediating leukocyte-platelet interactions.
      JAM-3 thereby provides a novel molecular target for antagonizing interactions
      between vascular cells that promote inflammatory vascular pathologies such as in
      atherothrombosis.

PMID- 12208883
TI  - The biological outcome of CD40 signaling is dependent on the duration of CD40
      ligand expression: reciprocal regulation by interleukin (IL)-4 and IL-12.
AB  - CD40 ligand (CD154) expression on activated T cells can be separated into an
      early TCR-dependent phase, which occurs between 0 and 24 h after activation, and
      a later extended phase, which occurs after 24 h and is reciprocally regulated by
      the cytokines IL-4 and IL-12. IL-4 represses, whereas IL-12 sustains CD154
      expression. Consistent with this, Th1, but not Th2, cells express CD154 for
      extended periods. Differences in the duration of CD154 expression have important
      biological consequences because sustained, but not transient, expression of CD154
      on activated T cells can prevent B cell terminal differentiation. Thus, the
      differential ability of Th cells to sustain CD154 expression is an important part
      of their helper function and should influence the activities of other CD40
      expressing cell types.

PMID- 12208884
TI  - The earliest step in B lineage differentiation from common lymphoid progenitors
      is critically dependent upon interleukin 7.
AB  - Little is known about the signals that promote early B lineage differentiation
      from common lymphoid progenitors (CLPs). Using a stromal-free culture system, we
      show that interleukin (IL)-7 is sufficient to promote the in vitro
      differentiation of CLPs into B220(+) CD19(+) B lineage progenitors. Consistent
      with current models of early B cell development, surface expression of B220 was
      initiated before CD19 and was accompanied by the loss of T lineage potential. To
      address whether IL-7 receptor (R) activity is essential for early B lineage
      development in vivo, we examined the frequencies of CLPs and downstream pre-pro-
      and pro-B cells in adult mice lacking either the alpha chain or the common gamma
      chain (gamma(c)) of the IL-7R. The data indicate that although gamma(c)(-/-) mice
      have normal frequencies of CLPs, both gamma(c)(-/-) and IL-7R(alpha)(-/-) mice
      lack detectable numbers of all downstream early B lineage precursors, including
      pre-pro-B cells. These findings challenge previous notions regarding the point in
      B cell development affected by the loss of IL-7R signaling and suggest that IL-7
      plays a key and requisite role during the earliest phases of B cell development.

PMID- 12208885
TI  - PC-SPES--a lesson for future dietary supplement research.

PMID- 12208886
TI  - More than spice: capsaicin in hot chili peppers makes tumor cells commit suicide.

PMID- 12208887
TI  - Contamination of PC-SPES remains a mystery.

PMID- 12208888
TI  - Cancer deaths in the United States attributable to smoking, 1995-1999.

PMID- 12208889
TI  - Cancer registries: should informed consent be required?

PMID- 12208890
TI  - Despite checkered past, thalidomide and its analogues show potential.

PMID- 12208891
TI  - A one-two punch: light-based therapy finds tumors, delivers treatment.

PMID- 12208892
TI  - Herbal composition PC-SPES for management of prostate cancer: identification of
      active principles.
AB  - BACKGROUND: The herbal mixture PC-SPES, used to manage advanced prostate cancer,
      has proven thrombogenic and highly estrogenic in clinical trials. However,
      attempts to identify the active compounds in PC-SPES have yielded incongruous
      results. Moreover, warfarin was identified in the serum of a patient taking PC
      SPES who experienced a bleeding disorder. To determine the active components in
      PC-SPES potentially responsible for these effects, we analyzed PC-SPES lots
      manufactured from l996 through mid-2001. METHODS: Antineoplastic activity of PC
      SPES and its individual component extracts was determined by colony-forming
      assays with several prostate cancer cell lines, and estrogenicity was determined
      by analyzing expression of an estrogen-responsive reporter gene in breast cancer
      cells. High-pressure liquid chromatography was used to isolate, identify, and
      quantify components of PC-SPES. Components were also identified by proton nuclear
      magnetic resonance, gas chromatography/mass spectrometry, and mass spectra
      analysis. RESULTS: PC-SPES lots manufactured from 1996 through mid-1999 contained
      the synthetic compounds indomethacin (range = 1.07-13.19 mg/g) and
      diethylstilbestrol (range = 107.28-159.27 micro g/g) and were two to six times
      more antineoplastic and up to 50 times more estrogenic than lots manufactured
      after the spring of 1999. In lots manufactured after mid-1999, gradual declines
      in the concentrations of indomethacin (from 1.56 to 0.70 mg/g),
      diethylstilbestrol (from 46.36 to 0.00 micro g/g), and total phytosterols (from
      0.586 to 0.085 mg/g) were observed. Warfarin was identified for the first time in
      lots manufactured after July 1998 (range = 341-560 micro g/g). In the August 2001
      lot, increases were found in concentrations of the natural products licochalcone
      A (from 27.6 to 289.2 micro g/g) and baicalin (from 12.5 to 38.8 mg/g).
      CONCLUSIONS: The phytochemical composition of PC-SPES varied by lot, and chemical
      analyses detected various amounts of the synthetic drugs diethylstilbestrol,
      indomethacin, and warfarin and several natural products. To qualify for clinical
      pharmacologic exploration, nutritional supplements including herbal mixtures
      should meet standards of quality control under the Good Manufacturing Practice
      system, and the manufacturers of such supplements should provide reliable
      analytical quality assurance.

PMID- 12208893
TI  - Examining the role of mitochondrial respiration in vanilloid-induced apoptosis.
AB  - BACKGROUND: The vanilloids capsaicin and resiniferatoxin are natural products
      that contain a vanillyl moiety (4-hydroxy-3-methoxybenzyl). Both vanilloids can
      induce apoptosis in certain cell types by a mechanism that has not been fully
      elucidated but may involve plasma membrane or mitochondrial targets. We
      investigated the role of mitochondrial respiration in vanilloid-induced
      apoptosis. METHODS: Cytofluorometric analysis was used to evaluate the effects of
      vanilloids on apoptosis, Ca(2+) mobilization, hydroperoxide generation, and DNA
      content in cells from two human cutaneous squamous cell carcinoma (SCC) cell
      lines (parental cells) and in their respiration-deficient clones. Oxygen
      consumption by the cells was determined polarographically. RESULTS: The majority
      of the parental SCC cells underwent apoptosis after a 12-hour exposure to 100
      micro M capsaicin or 10 micro M resiniferatoxin. The induction of apoptosis was
      associated with the mitochondrial permeability transition (i.e., an increase in
      the permeability of the inner mitochondrial membrane associated with the opening
      of a nonspecific pore). Exposure of parental cells to either vanilloid was not
      associated with an increase in intracellular free Ca(2+) levels but was
      associated with a rapid increase in hydroperoxide generation and a decrease in
      oxygen consumption. After vanilloid treatment, the respiration-deficient clones
      generated less hydroperoxide and were resistant to the mitochondrial permeability
      transition and the induction of apoptosis. Moreover, vanilloid treatment
      inhibited cell proliferation in the respiration-deficient clones by promoting
      G(1) arrest. CONCLUSIONS: Vanilloid-induced apoptosis in the parental SCC cells
      appears to involve the inhibition of mitochondrial respiration. The apoptogenic
      effects promoted by vanilloid treatment in parental SCC cells, as well as the
      antiproliferative effects observed in their respiration-deficient clones, suggest
      that vanilloids may be useful for preventing or treating skin cancers or other
      hyperproliferative skin disorders.

PMID- 12208894
TI  - Dietary sugar, glycemic load, and pancreatic cancer risk in a prospective study.
AB  - BACKGROUND: Evidence from both animal and human studies suggests that abnormal
      glucose metabolism plays an important role in pancreatic carcinogenesis. We
      investigated whether diets high in foods that increase postprandial glucose
      levels are associated with an increased risk of pancreatic cancer. METHODS: In a
      cohort of U.S. women (n = 88 802) participating in the Nurses' Health Study, 180
      case subjects with pancreatic cancer were diagnosed during 18 years of follow-up.
      We used frequency of intake of individual foods as reported on a food-frequency
      questionnaire in 1980 to calculate sucrose, fructose, and carbohydrate intakes;
      glycemic index (postprandial blood glucose response as compared with a reference
      food); and glycemic load (glycemic index multiplied by carbohydrate content).
      Analyses of relative risk (RR) were performed by using multivariable Cox
      proportional hazards models to adjust for potential confounders. All statistical
      tests were two-sided. RESULTS: Carbohydrate and sucrose intake were not
      associated with overall pancreatic cancer risk in this cohort. A statistically
      nonsignificant 53% increase in risk of pancreatic cancer (RR = 1.53, 95%
      confidence interval [CI] = 0.96 to 2.45) was observed among women with a high
      glycemic load intake, and a similar association was observed for fructose intake
      (RR = 1.57, 95% CI = 0.95 to 2.57). The associations of glycemic load and
      fructose intakes with pancreatic cancer risk were most apparent among women with
      elevated body mass index (>or=25 kg/m(2)) or with low physical activity. Among
      women who were both overweight and sedentary, a high glycemic load was associated
      with an RR of 2.67 (95% CI = 1.02 to 6.99; highest versus lowest quartile of
      intake; P for trend =.03), and high fructose was associated with an RR of 3.17
      (95% CI = 1.13 to 8.91; P for trend =.04). CONCLUSION: Our data support other
      findings that impaired glucose metabolism may play a role in pancreatic cancer
      etiology. A diet high in glycemic load may increase the risk of pancreatic cancer
      in women who already have an underlying degree of insulin resistance.

PMID- 12208895
TI  - Intake of dairy products, calcium, and vitamin d and risk of breast cancer.
AB  - BACKGROUND: Laboratory data suggest that calcium and vitamin D, found at high
      levels in dairy products, might reduce breast carcinogenesis. However,
      epidemiologic studies regarding dairy products and breast cancer have yielded
      inconsistent results. We examined data from a large, long-term cohort study to
      evaluate whether high intake of dairy products, calcium, or vitamin D is
      associated with reduced risk of breast cancer. METHODS: We followed 88 691 women
      in the Nurses' Health Study cohort from the date of return of their food
      frequency questionnaire in 1980 until May 31, 1996. Dietary information was
      collected in 1980 and updated in 1984, 1986, 1990, and 1994. We identified 3482
      women (premenopausal = 827, postmenopausal = 2345, and uncertain menopausal
      status = 310) with incident invasive breast cancer. We used pooled logistic
      regression to estimate multivariable relative risks (RRs) using 2-year time
      increments. The RRs and 95% confidence intervals (CIs) were calculated for each
      category of intake compared with the lowest intake group. All statistical tests
      were two-sided. RESULTS: Intakes of dairy products, calcium, or vitamin D were
      not statistically significantly associated with breast cancer risk in
      postmenopausal women. In premenopausal women, however, consumption of dairy
      products, especially of low-fat dairy foods and skim/low-fat milk, was inversely
      associated with risk of breast cancer. The multivariable RRs comparing highest
      (>1 serving/day) and lowest (<or=3 servings/month) intake categories were 0.68
      (95% CI = 0.55 to 0.86) for low-fat dairy foods and 0.72 (95% CI = 0.56 to 0.91)
      for skim/low-fat milk. Dairy calcium (>800 mg/day versus <or=200 mg/day; RR =
      0.69, 95% CI = 0.48 to 0.98), total vitamin D (>500 IU/day versus <or=150 IU/day;
      RR = 0.72, 95% CI = 0.55 to 0.94), and lactose (quintile 5 versus quintile 1; RR
      = 0.68, 95% CI = 0.54 to 0.86] also had inverse associations with premenopausal
      breast cancer risk. By taking into account supplemental calcium and vitamin D
      intake, we found that association with calcium was due mainly to dairy sources
      whereas the association with vitamin D may be independent of dairy intake.
      CONCLUSIONS: We found no association between intake of dairy products and breast
      cancer in postmenopausal women. Among premenopausal women, high intake of low-fat
      dairy foods, especially skim/low-fat milk, was associated with reduced risk of
      breast cancer. Similar inverse associations were seen with components (calcium
      and vitamin D) of dairy foods, but their independent associations with breast
      cancer are difficult to distinguish.

PMID- 12208896
TI  - Effects of vitamin D(3)-binding protein-derived macrophage activating factor
      (GcMAF) on angiogenesis.
AB  - BACKGROUND: The vitamin D(3)-binding protein (Gc protein)-derived macrophage
      activating factor (GcMAF) activates tumoricidal macrophages against a variety of
      cancers indiscriminately. We investigated whether GcMAF also acts as an
      antiangiogenic factor on endothelial cells. METHODS: The effects of GcMAF on
      angiogenic growth factor-induced cell proliferation, chemotaxis, and tube
      formation were examined in vitro by using cultured endothelial cells (murine IBE
      cells, porcine PAE cells, and human umbilical vein endothelial cells [HUVECs])
      and in vivo by using a mouse cornea micropocket assay. Blocking monoclonal
      antibodies to CD36, a receptor for the antiangiogenic factor thrombospondin-1,
      which is also a possible receptor for GcMAF, were used to investigate the
      mechanism of GcMAF action. RESULTS: GcMAF inhibited the endothelial cell
      proliferation, chemotaxis, and tube formation that were all stimulated by
      fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor-A, or
      angiopoietin 2. FGF-2-induced neovascularization in murine cornea was also
      inhibited by GcMAF. Monoclonal antibodies against murine and human CD36 receptor
      blocked the antiangiogenic action of GcMAF on the angiogenic factor stimulation
      of endothelial cell chemotaxis. CONCLUSIONS: In addition to its ability to
      activate tumoricidal macrophages, GcMAF has direct antiangiogenic effects on
      endothelial cells independent of tissue origin. The antiangiogenic effects of
      GcMAF may be mediated through the CD36 receptor.

PMID- 12208898
TI  - Risk of subsequent cancer following breast cancer in men.
AB  - The etiology of breast cancer in men is not well understood. We assessed the risk
      of subsequent cancers among all 1788 men diagnosed with a first primary breast
      cancer from 1973 through 1996 who were registered with the Surveillance,
      Epidemiology, and End Results (SEER) Program. Although the overall subsequent
      cancer risk in men was not increased (standardized incidence ratio [SIR] = 0.99,
      95% confidence interval [CI] = 0.86 to 1.1), the risk of contralateral second
      breast cancer was strongly elevated (12 cases; SIR = 30, 95% CI = 15 to 52). The
      risk was higher for men diagnosed with their first breast cancer before age 50
      years than for older men. There were no major differences in the risk of
      contralateral breast cancer associated with different treatments received for the
      first breast cancer. The relative risk of second breast cancer was substantially
      higher among men than among women with breast cancer, but the absolute excess
      risk was lower. We conclude that men diagnosed with breast cancer are at high
      risk of contralateral breast cancer.

PMID- 12208897
TI  - Amplification/overexpression of a mitotic kinase gene in human bladder cancer.
AB  - BACKGROUND: The mitotic kinase-encoding gene STK15/BTAK/ AuroraA is associated
      with aneuploidy and transformation when overexpressed in mammalian cells. STK15
      overexpression activates an unknown oncogenic pathway that involves centrosome
      amplification and results in missegregation of chromosomes. Because clinical
      prognosis and tumor aneuploidy are tightly linked in human bladder cancer, we
      examined whether increased STK15 copy number and protein levels are linked to
      aneuploidy in bladder cancers. METHODS: STK15 protein was visualized by
      immunohistochemistry in 205 formalin-fixed, paraffin-embedded human bladder
      tumors. STK15 gene copy number was evaluated in 61 tumors by Southern blot
      hybridization and in 21 of these 61 tumors by fluorescence in situ hybridization
      (FISH). Copy numbers of chromosomes 3, 17, 20, and 21 were evaluated by FISH with
      chromosome-specific probes. STK15 expression levels were related to histologic
      grade, stage, and DNA ploidy of the tumors and to the patients' follow-up data.
      The chi-square test for association was used to analyze the relationship between
      STK15 expression and pathologic features. All statistical tests were two-sided.
      RESULTS: Tumors with low levels of STK15 amplification (3-4 copies) showed
      minimal deviation in their chromosome copy number and diploid or near-diploid
      total nuclear DNA content. Tumors with higher levels of STK15 amplification (>4
      copies) had a major increase of chromosome copy number and of their total nuclear
      DNA content, i.e., exhibited pronounced aneuploidy. Elevated expression of STK15
      was strongly associated with parameters of clinical aggressiveness including high
      histologic grade (P<.001), invasion (P<.001), increased rate of metastasis
      (P<.001), and decreased metastasis-free (P<.001) and overall (P<.001) survival of
      patients with bladder cancer. CONCLUSION: STK15 gene amplification and associated
      increased expression of the mitotic kinase it encodes are associated with
      aneuploidy and aggressive clinical behavior in human bladder cancer.

PMID- 12208899
TI  - High titers of anti-human herpesvirus 8 antibodies in elderly males in an endemic
      population.
AB  - Human herpesvirus 8 (HHV8) is the etiologic agent of Kaposi's sarcoma (KS), a
      tumor occurring mainly among elderly men in its endemic and classical forms. The
      male-to-female ratio of KS in different endemic populations ranges from 3 : 1 to
      15 : 1. We investigated the influence of age and gender on anti-HHV8 antibody
      titers among HHV8-seropositive subjects of an endemic population (1819 villagers
      with 874 men and 945 women) of African origin living in French Guiana. By using a
      specific immunofluorescence assay, we found that the overall HHV8 seroprevalence
      of antibodies against lytic antigens was 11.8%. There was no difference between
      seroprevalence in males (11.7%) and females (11.8%). Among the 214 HHV8
      seropositive subjects, anti-HHV8 antibody titers were found to increase with age
      (P<.001) and were higher in males than in females (P =.003). The geometric mean
      of HHV8 antibody titers was 1 : 105 (95% confidence interval [CI] = 1 : 77 to 1 :
      144) for males versus 1 : 62 (95% CI = 1 : 47 to 1 : 81) for females. The titers
      increased from 1 : 59 (95% CI = 1 : 43 to 1 : 80) in males younger than 40 years
      to 1 : 452 (95% CI = 1 : 244 to 1 : 839) in the oldest male group (aged 50 years
      and older). Such high antibody titers directed against lytic antigens in males
      aged 40 years and older parallel the increase of endemic KS incidence in older
      African men. Our results suggest that the role of gender should also be
      considered in evaluating the association between anti-HHV8 antibody titers in
      people aged 40 years and older and the risk of developing KS.

PMID- 12208900
TI  - Re: The effects of tamoxifen and estrogen on brain metabolism in elderly women.

PMID- 12208902
TI  - Re: 1,1-Dichloro-2,2-bis-(p-chlorophenyl)ethylene and polychlorinated biphenyls
      and breast cancer: combined analysis of five U.S. studies.

PMID- 12208905
TI  - Anterior cruciate ligament replacement: comparison of bone-patellar tendon-bone
      grafts with two-strand hamstring grafts. A prospective, randomized study.
AB  - BACKGROUND: The purpose of this investigation was to evaluate replacement of a
      torn anterior cruciate ligament with either a bone-patellar tendon-bone autograft
      or a two-strand semitendinosus-gracilis autograft to compare the results of
      clinical testing, patient satisfaction, activity level, functional status, and
      muscle strength. METHODS: Fifty-six patients with a torn anterior cruciate
      ligament were enrolled in a prospective, randomized, controlled study. Twenty
      eight underwent reconstruction with a bone-patellar tendon-bone autograft, and
      twenty-eight were treated with a two-strand semitendinosus-gracilis autograft.
      Patients were followed for an average of thirty-nine months (range, thirty-six to
      fifty-seven months). At the time of final follow-up, twenty-two patients in each
      group were evaluated in terms of clinical test findings, patient satisfaction,
      activity level, functional status, and isokinetic muscle strength. RESULTS: The
      objective outcome of replacement of the torn anterior cruciate ligament with a
      bone-patellar tendon-bone graft was superior to that obtained with a two-strand
      semitendinosus-gracilis graft. At the three-year follow-up interval, the patients
      in whom a hamstring graft had been used had an average of 4.4 mm of increased
      anterior knee laxity compared with the laxity of the contralateral, normal knee,
      whereas the patients in whom a bone-patellar tendon-bone graft had been used had
      an average of 1.1 mm of increased knee laxity. Fourteen percent (three) of the
      twenty-two patients with a hamstring graft had a mild pivot shift, and 27% (six)
      had a moderate pivot shift. Only 14% (three) of the twenty-two patients with a
      bone-patellar tendon-bone graft had a mild pivot shift, and none had a moderate
      pivot shift. At the same follow-up interval, the patients in whom a hamstring
      graft had been used had significantly lower peak knee-flexion strength than those
      who had a bone-patellar tendon-bone graft (p = 0.039). In contrast, the two
      treatments produced similar outcomes in terms of patient satisfaction, activity
      level, and knee function (ability to perform a one-legged hop, bear weight,
      squat, climb stairs, run in place, and duckwalk). CONCLUSIONS: After three years
      of follow-up, the objective results of anterior cruciate ligament replacement
      with a bone-patellar tendon-bone autograft were superior to those of replacement
      with a two-strand semitendinosus-gracilis graft with regard to knee laxity, pivot
      shift grade, and strength of the knee flexor muscles. However, the two groups had
      comparable results in terms of patient satisfaction, activity level, and knee
      function.

PMID- 12208906
TI  - Femoral intramedullary nailing: comparison of fracture-table and manual traction.
      a prospective, randomized study.
AB  - BACKGROUND: The purpose of this study was to compare manual traction and fracture
      table traction for the reduction and nailing of femoral shaft fractures. We
      evaluated the quality of the reduction, operative time, complications, and
      functional status of the patient. METHODS: Eighty-seven consecutive adult
      patients with a unilateral fracture of the femoral diaphysis that did not extend
      into the knee joint or proximal to the lesser trochanter were enrolled in the
      study. Patients who were transferred to our institution more than forty-eight
      hours after injury; those with multiple-system injuries, injury to the
      ipsilateral lower extremity, or pathological fracture; and those who were unable
      or unwilling to provide consent or to return for follow-up were excluded. Forty
      five patients were randomized to manual traction and forty-two, to fracture-table
      traction; all were treated in the supine position. The number of surgical
      assistants, operative and fluoroscopy time, complications, functional scores, and
      other outcomes were recorded. RESULTS: There were no significant differences
      between the groups with respect to age, gender, Glasgow Coma Score, Injury
      Severity Score, side or mechanism of injury, fracture type, or time from injury
      to treatment. Internal malrotation was significantly more common when the
      fracture table had been used: twelve (29%) of the forty-two femora were
      internally rotated by >10  compared with three (7%) of the forty-five treated
      with manual traction (p = 0.007). Total operative time, from the beginning of the
      patient positioning to the completion of the skin closure, was decreased from a
      mean of 139 minutes (range, 100 to 212 minutes) when the fracture table was used
      to a mean of 119 minutes (range, sixty-five to 180 minutes) when manual traction
      was used (p = 0.033). There was no significant difference between the two
      treatment groups with regard to the number of assistants per case (mean two;
      range, zero to three), fluoroscopy time, other complications including femoral
      shortening or lengthening, or functional status of the patient at one year.
      CONCLUSIONS: Compared with fracture-table traction with the patient in a supine
      position, manual traction for intramedullary nailing of isolated fractures of the
      femoral shaft is an effective technique that decreases operative time and
      improves the quality of the reduction.

PMID- 12208907
TI  - Accuracy of needle placement into the intra-articular space of the knee.
AB  - BACKGROUND: To achieve their potential therapeutic benefit, hyaluronic acid
      derivatives should be injected directly into the knee joint space and not into
      the anterior fat pad or the subsynovial tissues. In the absence of a knee
      effusion, reproducible needle placement into the intra-articular space presents a
      challenge to the clinician. METHODS: The accuracy of needle placement was
      assessed in a prospective series of 240 consecutive injections in patients
      without clinical knee effusion. The injections were performed by one orthopaedic
      surgeon using a 2.0-in (5.1-cm) 21-gauge needle through three commonly employed
      knee joint portals: anteromedial, anterolateral, and lateral midpatellar.
      Accuracy rates for needle placement were confirmed with fluoroscopic imaging to
      document the dispersion pattern of injected contrast material. RESULTS: Of eighty
      injections performed through an anterolateral portal, fifty-seven were confirmed
      to have been placed in the intra-articular space on the first attempt (an
      accuracy rate of 71%). Sixty of eighty injections performed through an
      anteromedial approach were intra-articular on the first attempt (75% accuracy
      rate), as were seventy-four of eighty injections performed through a lateral
      midpatellar portal (93% accuracy rate). CONCLUSIONS: Using real-time fluoroscopic
      imaging with contrast material, we demonstrated the difficulty of accurately
      placing a needle into the intra-articular space of the knee when an effusion is
      not present. This study revealed that a lateral midpatellar injection (an
      injection into the patellofemoral joint) was intra-articular 93% of the time and
      was more accurate than injections performed by the same orthopaedic surgeon using
      either of the other two portals. This study highlights the need for clinicians to
      refine injection techniques for delivering intra-articular therapeutic substances
      that are intended to coat the articular surfaces of the knee joint.

PMID- 12208908
TI  - Refractures in patients at least forty-five years old. a prospective analysis of
      twenty-two thousand and sixty patients.
AB  - BACKGROUND: Individuals who sustain a low-energy fracture are at increased risk
      of sustaining a subsequent low-energy fracture. The incidence of these
      refractures may be reduced by secondary preventative measures, although
      justifying such interventions and evaluating their impact is difficult without
      substantive evidence of the severity of the refracture risk. The aim of this
      study was to quantify the risk of sustaining another fracture following a low
      energy fracture compared with the risk in an age and sex-matched reference
      population. METHODS: During the twelve-year period between January 1988 and
      December 1999, all inpatient and outpatient fracture-treatment events were
      prospectively audited in a trauma unit that is the sole source of fracture
      treatment for a well-defined local catchment population. During this time, 22,060
      patients at least forty-five years of age who had sustained a total of 22,494 low
      energy fractures of the hip, wrist, proximal part of the humerus, or ankle were
      identified. All refracture events were linked to the index fracture in the
      database during the twelve-year period. The incidence of refracture in the cohort
      of patients who had sustained a previous fracture was divided by the "background"
      incidence of index fractures within the same local population to obtain the
      relative risk of refracture. Person-years at-risk methodology was used to control
      for the effect of the expected increase in mortality with advancing age. RESULTS:
      Within the cohort, 2913 patients (13.2%) subsequently sustained a total of 3024
      refractures during the twelve-year period. Patients with a previous low-energy
      fracture had a relative risk of 3.89 of sustaining a subsequent low-energy
      fracture. The relative risk was significantly increased for both sexes, but it
      was greater for men (relative risk = 5.55) than it was for women (relative risk =
      2.94). The relative risk was 5.23 in the youngest age cohort (patients between
      forty-five and forty-nine years of age), and it decreased with increasing age to
      1.20 in the oldest cohort (patients at least eighty-five years of age).
      CONCLUSIONS: Individuals who sustain a low-energy fracture between the ages of
      forty-five and eighty-four years have an increased relative risk of sustaining
      another low-energy fracture. This increased risk was greater when the index
      fracture occurred earlier in life; the risk decreased with advancing age.
      Secondary preventative measures designed to reduce the risk of refracture
      following a low-energy fracture are likely to have a greater impact on younger
      individuals.

PMID- 12208909
TI  - Surface damage in machined ram-extruded and net-shape molded retrieved
      polyethylene tibial inserts of total knee replacements.
AB  - BACKGROUND: Polyethylene wear has emerged as a major determining factor in the
      long-term clinical performance of total knee replacements. This study addresses
      the in vivo wear performance of two types of polyethylene tibial inserts used in
      similar total knee arthroplasty designs. METHODS: A surface damage assessment of
      retrieved specimens was performed for twenty-six net-shape molded tibial inserts
      manufactured from H1900 resin without calcium stearate additive (Miller-Galante)
      and forty-three machined ram-extruded tibial inserts manufactured from GUR 4150
      resin with calcium stearate additive (Miller-Galante II). Stereomicroscopic
      inspection and digital image analysis were used to quantify the extent and
      severity of pitting, dimensional change, and delamination. RESULTS: Pitting and
      dimensional change were the most common modes of damage in both groups, with the
      prevalence ranging from 77% to 92% for pitting and from 51% to 81% for
      dimensional change. Delamination was the least common mode of damage, with the
      prevalence ranging from 21% to 35%. The severity of pitting was higher in
      association with the cemented implant-bone interface. The extent and severity of
      delamination increased with implantation time. No severe delamination was
      observed before sixty months after implantation in the net-shape molded group,
      whereas severe delamination was present as early as ten months after implantation
      in the machined ram-extruded group. The time between surgery and the discovery of
      damage was longer in the net-shape molded group for all modes of damage except
      for medial dimensional change. CONCLUSIONS: On the basis of the components
      available in our implant retrieval pool, we found that at equivalent levels of
      surface damage, the net-shape molded H1900 resin tibial inserts demonstrated
      longer service life than did the machined ram-extruded GUR 4150 components. The
      superior performance of the net-shape molded components may be related to the
      resin type, the absence of calcium stearate, the consolidation method, or the
      method of final geometry shaping. This superior damage resistance is expected to
      contribute to superior long-term clinical performance of net-shape molded ultra
      high molecular weight polyethylene in total knee arthroplasty.

PMID- 12208910
TI  - High-energy fractures of the tibial plateau. Knee function after longer follow
      up.
AB  - BACKGROUND: Studies of the long-term outcomes of treatment of fractures of the
      tibial plateau have included wide mixtures of fracture types and mostly low
      energy split and split-depression fractures. The long-term results of treatment
      of high-energy intra-articular proximal tibial fractures are unknown. The purpose
      of this study was to assess the function of the knee and the development of
      arthrosis at a minimum of five years after injury in a consecutive series of
      patients in whom a high-energy fracture of the tibial plateau had been treated
      with a uniform technique of external fixation. METHODS: Between July 1988 and
      December 1994, thirty patients with a total of thirty-one fractures of the tibial
      plateau were treated with a monolateral external fixator and limited internal
      fixation of the articular surface. Follow-up data on twenty-four knees in twenty
      three patients were obtained at a mean of ninety-eight months. Twenty patients
      (twenty knees) returned specifically for the study, at which time they completed
      an Iowa Knee Score questionnaire and a Short Form-36 (SF-36) general health
      survey, a physical examination was performed, and weight-bearing radiographs were
      made. The results of the SF-36 evaluations for fourteen patients and the Knee
      Scores for twelve were compared with those obtained five years previously, at two
      to four years after the injury. RESULTS: After healing, no patient required a
      secondary reconstructive procedure. The range of motion of the knee averaged 3
      degrees of extension to 120 degrees flexion, which was an average of 87% of the
      total arc of the contralateral knee. The average Iowa Knee Score was 90 points
      (range, 72 to 100 points). For twelve patients, the Iowa Knee Score previously
      recorded at two to four years averaged 92 points, as did the score at the time of
      the latest follow-up. Thirteen patients rated their outcome as excellent; six, as
      good; and three, as fair. Fifteen patients were working, and ten of them were
      performing strenuous labor. Radiographs showed no evidence of arthrosis in
      fourteen knees, grade-1 arthrosis in three, grade-2 in three, and grade-3 in two.
      Compared with the radiographic appearance two to four years after injury, there
      was no evidence of progression of arthrosis in eighteen knees and one grade of
      progression in four. The SF-36 subscale scores were similar to those of age
      matched controls. The fourteen patients who had previous SF-36 scores had no
      deterioration of these scores. CONCLUSIONS: Patients with a high-energy fracture
      of the tibial plateau treated with external fixation have a good prognosis for
      satisfactory knee function in the second five years after injury. The knee joint
      cartilage appears to be tolerant of both the injury and mild-to-moderate residual
      articular displacement, which was associated with a low rate of severe arthrosis.

PMID- 12208911
TI  - Redislocation of the shoulder during the first six weeks after a primary anterior
      dislocation: risk factors and results of treatment.
AB  - BACKGROUND: After an anterior dislocation, shoulder instability may occur with
      disruption of the soft-tissue or osseous restraints, leading to early
      redislocation. The aim of the present study was to clarify the risk factors for
      this complication within the first six weeks after a first-time anterior
      traumatic dislocation and to assess the outcome of treatment with immediate
      operative stabilization. METHODS: A three-year, prospective, observational cohort
      study of 538 consecutive patients with a first-time anterior dislocation of the
      shoulder was carried out. Reassessment of shoulder function was performed at a
      dedicated shoulder clinic, and suspected early redislocations were assessed with
      additional radiographs. All medically fit patients with a confirmed acute
      redislocation were treated with repeat closed reduction under anesthesia.
      Patients with unstable reductions were treated operatively. Functional and
      radiographic assessment of outcome was carried out during the first year after
      dislocation. RESULTS: Seventeen (3.2%) of the 538 patients sustained an early
      redislocation within the first week after the original dislocation. Patients at
      increased risk of early redislocation included those who sustained the original
      dislocation as the result of a high-energy injury (relative risk = 13.7), those
      who had a neurological deficit (relative risk = 2.0), those in whom a large
      rotator cuff tear occurred in conjunction with the dislocation (relative risk =
      29.8), those in whom the original dislocation was associated with a fracture of
      the glenoid rim (relative risk = 7.0), and those who had a fracture of both the
      glenoid rim and the greater tuberosity (relative risk = 33.5). Following
      operative reconstruction, the outcome at one year after the injury was favorable
      in terms of function, general health, and radiographic findings. None of the
      patients had a redislocation or symptoms of instability at one year. CONCLUSION:
      All patients who have substantial pain, a visible shoulder deformity, or
      restriction of movement at one week after reduction of a first-time dislocation
      should be evaluated with repeat radiographs to exclude a redislocation. Patients
      in whom this complication develops usually have either (1) severe disruption of
      the soft-tissue envelope due to a large rotator cuff tear or (2) disruption of
      the normal osseous restraints to dislocation due to either an isolated fracture
      of the glenoid rim or fractures of both the glenoid rim and the greater
      tuberosity. Early operative stabilization is justified for patients in whom the
      dislocation is associated with these coexisting conditions and who have evidence
      of gross instability.

PMID- 12208912
TI  - Determinants of patient satisfaction with outcome after anterior cruciate
      ligament reconstruction.
AB  - BACKGROUND: The purpose of this study was to identify the determinants of patient
      satisfaction with the outcome after reconstruction of the anterior cruciate
      ligament. METHODS: A cohort of 201 patients undergoing primary reconstruction of
      the anterior cruciate ligament was studied prospectively. All patients were
      followed for a minimum of two years (mean, 35.9 months). The dependent variable
      was patient satisfaction with the outcome, graded ordinally on a scale of 1 to
      10. Nonparametric univariate analysis and multivariable modeling were performed
      to identify determinants of satisfaction. RESULTS: The demographic variables were
      not found to have a significant association (p > 0.05) with patient satisfaction.
      The variables at surgery demonstrated a significant association (p < 0.05) with
      patient satisfaction only with respect to the status of the lateral meniscus, the
      presence of osteophytes, and concurrent plica excision. The objective variables
      at follow-up revealed that patients were significantly less satisfied (p < 0.05)
      if they had a flexion contracture, increased laxity of the involved leg on the
      manual maximum test as measured on a KT-1000 device, an abnormal result on the
      pivot-shift examination, effusion, or tenderness at the medial joint line or
      patella. With regard to the subjective symptoms at follow-up, patients were found
      to be significantly (p < 0.05) less satisfied with the outcome if they had
      symptoms of pain, swelling, partial giving-way, full giving-way, locking, noise,
      stiffness, or a limp. Analysis of the subjective function at follow-up
      demonstrated that patients were significantly less satisfied (p < 0.05) with the
      outcome if they had a lower level of activity, sports activity, strenuous work,
      activities of daily living, overall knee function, sports participation, or
      symptom-free activity; if they were unemployed; or if they had difficulty with
      walking, squatting, ascending or descending stairs, running, jumping, cutting, or
      twisting. Patient satisfaction was significantly associated (p < 0.05) with the
      Lysholm knee score, overall International Knee Documentation Committee (IKDC)
      knee score, IKDC subjective subscore, IKDC symptoms subscore, and IKDC range-of
      motion subscore. The seven independent multivariate determinants (adjusted R (2)
      = 0.83, p < 0.001) of patient satisfaction included the Lysholm score, overall
      subjective knee function, IKDC range-of-motion subscale, patellar tenderness,
      full giving-way, flexion contracture, and swelling. CONCLUSIONS: Univariate and
      multivariate determinants of patient satisfaction with the outcome after
      reconstruction of the anterior cruciate ligament were established. Although some
      specific surgical and objective variables were important, subjective variables of
      symptoms and function had the most robust associations with patient satisfaction.
      In assessing the outcome of reconstruction from the perspective of patient
      satisfaction with the outcome, we should emphasize patient-derived subjective
      assessment of symptoms and function, particularly those involving issues of
      stiffness, giving-way, swelling, and patellofemoral symptoms.

PMID- 12208913
TI  - Ice reduces edema. A study of microvascular permeability in rats.
AB  - BACKGROUND: Ice is applied following a soft-tissue injury on the basis of
      clinical information. This study investigates the relationship between ice
      therapy (cryotherapy) and edema by determining microvascular permeability before
      and after contusion with and without ice therapy and provides data supporting a
      reduction in edema following cryotherapy. METHODS: A dorsal microvascular chamber
      was created in rats to allow the direct examination of microvascular parameters
      in intact, pre-established microvascular beds of the cutaneous maximus muscle in
      conscious rats. The rats received a contusion or sham contusion and were treated
      with cryotherapy or were not treated. Microvascular permeability (edema) was
      assessed by measuring fluorescent-labeled albumin in the interstitial fluid
      before and after contusion. RESULTS: Microvascular permeability following
      contusion was significantly increased in the group that received the contusion
      without cryotherapy compared with that in the group that received the sham
      contusion without cryotherapy (control) (p < 0.001). When ice was applied fifteen
      minutes after the contusion for twenty minutes, microvascular permeability
      (edema) decreased significantly (p < 0.001) compared with that in the group that
      did not receive cryotherapy after contusion. Permeability was increased in the
      group that received cryotherapy following the contusion compared with that in the
      control group (p = 0.012), although the increase was not as great as that between
      the group that received the contusion without cryotherapy and the control group.
      Sham contusion with cryotherapy significantly reduced microvascular permeability
      compared with that in the control group (p = 0.004). Sham contusion without
      cryotherapy did not cause a significant change in the microvascular permeability
      of postcapillary venules after 300 minutes compared with baseline measurements.
      CONCLUSIONS: The application of ice significantly decreased microvascular
      permeability following striated muscle contusion. The results of this study
      demonstrated that microvascular permeability is increased following a contusion
      coincident with significant leukocyte-endothelial interactions. However,
      microvascular permeability was significantly reduced following cryotherapy, a
      treatment demonstrated to reduce the number of rolling and adherent leukocytes.
      This association suggests that the reduction in edema in injured skeletal muscle
      following cryotherapy may be due to a reduction in leukocyte-endothelial
      interactions.

PMID- 12208914
TI  - A biomechanical analysis of fixation of intra-articular distal radial fractures
      with calcium-phosphate bone cement.
AB  - BACKGROUND: Calcium phosphate cement has been used to treat unstable fractures of
      the distal end of the radius with the intent of avoiding the stiffness and
      morbidity associated with prolonged immobilization in a cast or external
      fixation. The purpose of this study was to compare the stability of the fracture
      fragments after fixation with augmented calcium phosphate cement with that after
      alternative methods of percutaneous fracture treatment. METHODS: Both an
      osteotomy and osteoclasis were used to create a model of an intra-articular
      fracture of the distal part of the radius (AO type C2) with dorsal bone loss in
      seven pairs of fresh-frozen upper extremities. One wrist from each pair was fixed
      with an external fixator and three Kirschner wires, and the contralateral wrist
      was fixed with calcium phosphate cement (Norian SRS) and three Kirschner wires
      (augmented calcium phosphate cement). Sequentially increasing loads, up to a
      total of 100 N, were then applied to the major flexors and extensors of the
      wrist. Fracture fragment motion was measured by the Optotrak three-dimensional
      system. RESULTS: Fixation with cement alone failed at the bone-cement interface
      at <80 N in all specimens. With use of an analysis of variance, augmented
      external fixation was found to provide significantly increased stability to the
      radial fragment compared with that provided by augmented calcium phosphate cement
      in four of the six axes tested (e.g., mean motion [and standard deviation] in
      flexion-extension was 3.0 degrees +/- 2.93 degrees versus 11.1 degrees +/- 13.08
      degrees, respectively; p = 0.001). Augmented calcium phosphate cement was found
      to provide greater stability for the radial fragment than were Kirschner wires
      alone in three axes (e.g., mean motion in flexion-extension was 11.1 degrees +/-
      13.08 degrees versus 36.5 degrees +/- 13.03 degrees, respectively; p = 0.001).
      CONCLUSIONS: Calcium phosphate cement alone is insufficient to withstand
      physiologic flexion-extension motion of the wrist without supplemental wire
      fixation. When supplemented with Kirschner wires, fixation with bone cement is
      more stable than are Kirschner wires alone, but it is significantly less stable
      than augmented external fixation.

PMID- 12208915
TI  - Cementation of a polyethylene liner into a metal shell. Factors related to
      mechanical stability.
AB  - BACKGROUND: Various clinical situations may make polyethylene liner exchange
      desirable in the setting of a well-fixed metal shell. Options have included a
      simple polyethylene liner exchange or revision of the entire acetabular shell. A
      recently introduced technique involves cementation of a new liner into a well
      fixed metal shell. The purposes of this study were to quantify the mechanical
      integrity of this method of liner fixation, to evaluate the factors that may
      influence immediate liner fixation, and to compare this construct with a standard
      locking mechanism. METHODS: One modular acetabular cup design was evaluated.
      Variables that may contribute to the mechanical integrity of the construct were
      evaluated via lever-out and multiaxis dislocation testing methods. The variables
      included the size of the liner (undersized versus oversized), type of liner (all
      polyethylene versus modular design), modification of the modular liner
      (unmodified versus grooved), and groove configuration (cruciform versus
      circumferential). Metal shells with and without screw-holes were also tested. The
      modular locking mechanism was used as the control. RESULTS: None of the
      constructs failed at the cement-metal interface. All undersized liners required
      significantly higher loads to failure than either the controls (p < 0.001) or the
      oversized liners (p < 0.001). Oversized unmodified liners failed at significantly
      lower loads than the controls did (p < 0.01). The creation of circumferential
      grooves in the oversized liners significantly improved the strength of the
      constructs (p < 0.01), making them comparable with the controls. No significant
      differences were found among the four undersized groups (p > 0.3). The standard
      locking construct (control) and the oversized unmodified construct failed at a
      force of 2000 N in the multiaxis dislocation test. No other construct failed with
      use of this test mode. CONCLUSIONS: Cementation of a polyethylene liner into a
      metal shell can be stronger than a conventional locking mechanism if the liner is
      undersized. Cementation of an oversized liner into a shell should be performed
      with caution. The long-term durability of this fixation remains unknown.

PMID- 12208916
TI  - Periacetabular osteotomy through a modified ollier transtrochanteric approach for
      treatment of painful dysplastic hips.
AB  - BACKGROUND: Elimination of abnormally high joint-loading resulting in excessive
      contact stresses may prevent or reduce the onset of osteoarthrosis in a
      dysplastic hip. A number of periacetabular osteotomies have been shown to be
      effective in restoring normal hip-joint mechanics. We treat acetabular dysplasia
      with a periacetabular osteotomy performed through a modified Ollier
      transtrochanteric approach. In this report, we describe the operative technique
      and the clinical and radiographic results. METHODS: Thirty-six patients (thirty
      eight hips) in whom a painful dysplastic hip had been treated with a
      periacetabular osteotomy between March 1991 and June 1999 were included in the
      study. There were thirty-five female patients and one male patient with a mean
      age (and standard deviation) at the operation of 29.42 +/- 9.1 years. The
      technique utilizes a u-shaped skin incision, and a routine osteotomy of the
      greater trochanter with distal transfer if needed, and allows excellent
      visualization enabling the surgeon to perform the periacetabular osteotomy
      without penetrating the joint. RESULTS: At a mean of five years and six months
      postoperatively, the mean modified Harris hip score had improved from 59.1 +/-
      15.8 points preoperatively to 87.97 +/- 14.3 points. Radiographically, the degree
      of osteoarthrosis had decreased in eleven hips, remained unchanged in twenty
      four, and worsened in three. The mean anterior center-edge angle had increased
      from 22.0 degrees +/- 12.9 degrees to 36.1 degrees +/- 12.3 degrees, the mean
      lateral center-edge angle had increased from -2.7 degrees +/- 14.4 degrees to
      26.6 degrees +/- 14.1 degrees, the mean acetabular index angle had improved from
      23.4 degrees +/- 6.6 degrees to 12.7 degrees +/- 4.6 degrees, and the mean
      acetabular head index had increased from 48.2% +/- 12.7% to 73.1% +/- 16.0%. The
      Shenton line was restored in eleven hips. Thirty patients (thirty-two hips; 84%)
      had a satisfactory result. A poor preoperative functional score was associated
      with an unsatisfactory outcome (p = 0.00191). Complications included prolonged
      limping (eleven hips); numbness in the distribution of the lateral femoral
      cutaneous nerve (four); osteonecrosis of the rotated acetabular fragment (two);
      and acetabulofemoral impingement, heterotopic ossification, and a defect on the
      rotated ilium (one hip each). CONCLUSIONS: Painful dysplastic hips should be
      treated before function becomes seriously impaired. We believe that
      periacetabular osteotomy through a modified Ollier approach, which allows osseous
      cuts to be made under direct vision, can be learned readily. It provides improved
      femoral head coverage and relief of symptoms in most painful dysplastic hips in
      adolescents and young adults.

PMID- 12208917
TI  - Comparison of early and delayed fixation of subcapital hip fractures in patients
      sixty years of age or less.
AB  - BACKGROUND: Subcapital hip fractures in younger patients are generally treated
      with internal fixation rather than with primary hemiarthroplasty, which is
      generally reserved for older, low-demand patients. Avascular necrosis can occur
      following this injury because of disruption of the femoral head blood supply.
      Some believe that emergent fracture reduction is necessary to minimize the risk
      of avascular necrosis. The purposes of this study were (1) to investigate the
      functional outcomes of subcapital hip fractures in patients sixty years old or
      younger and (2) to compare the rates of avascular necrosis after early and
      delayed fracture fixation. METHODS: This retrospective study included adults in
      whom a subcapital hip fracture had been treated with reduction and internal
      fixation when they were sixty years of age or less and who had been followed
      clinically for a minimum of two years. The patients were divided into two groups:
      those treated with early fixation (within twelve hours after the injury) and
      those treated with delayed fixation (more than twelve hours after the injury).
      Functional outcomes were assessed with use of the Short Form-36 and the Western
      Ontario and McMaster University (WOMAC) Osteoarthritis Index. The rates of
      avascular necrosis were compared between the two groups. RESULTS: Thirty-eight
      patients (average age, 46.4 years) participated in the study. Twenty-nine
      patients had a displaced subcapital hip fracture. Fifteen patients underwent
      early fracture fixation, and the remainder underwent delayed fixation. No
      differences in the Short Form-36 (p = 0.68) or WOMAC (p = 0.69) scores were seen
      between the early and delayed fixation groups. Radiographic evidence of avascular
      necrosis developed in six patients treated with delayed fixation, one of whom had
      had an undisplaced fracture preoperatively, and in no patient treated with early
      fixation. The difference in the rates of avascular necrosis was significant (p =
      0.03). CONCLUSIONS: Although delayed surgical treatment of subcapital hip
      fractures was associated with a higher rate of avascular necrosis, this
      complication did not significantly affect functional outcome. Longer follow-up is
      required to assess the effect of avascular necrosis on the development of
      arthritis and on long-term patient function. Although the results could be biased
      because patients were not randomly assigned to delayed or early fixation, the
      data suggest that urgent reduction and fracture fixation within twelve hours
      after a displaced subcapital hip fracture in high-demand patients may be
      associated with a reduced rate of radiographic signs of avascular necrosis.

PMID- 12208918
TI  - Prospective reevaluation of the association between thrombotic diathesis and legg
      perthes disease.
AB  - BACKGROUND: Legg-Perthes disease is associated with ischemia of the capital
      femoral epiphysis in children. Thrombophilia has been implicated as a potential
      cause of the condition, and screening of patients with Legg-Perthes disease for
      thrombophilia has been recommended. We analyzed the value of screening for
      inherited thrombophilia in patients with Legg-Perthes disease by examining the
      association between Legg-Perthes disease and abnormalities in the thrombotic
      pathway. METHODS: A random series of consecutive patients with Legg-Perthes
      disease were prospectively enrolled in this study. Assays for the detection of
      factor-V Leiden mutation and the plasma concentrations of protein C, protein S,
      antithrombin III, and lipoprotein (a) were performed on plasma samples from
      children with Legg-Perthes disease, and the results were compared with those for
      pooled plasma from normal controls. Plasma concentrations below the 95% midrange
      of the control values were classified as protein deficiencies. The estimated
      population frequency of each coagulation abnormality was compared with the
      proportion of the study group with the corresponding abnormality. RESULTS: The
      proportion of abnormalities observed in the study group did not differ from the
      estimated population frequency for protein C, protein S, antithrombin III, or
      factor-V Leiden mutation. A lipoprotein (a) level of >30 mg/dL (>1.07 micro
      mol/L) was found in 16% of the study group. CONCLUSIONS: Our data do not suggest
      that thrombotic diatheses due to deficiency of protein C, protein S, or
      antithrombin III or due to factor-V Leiden mutation are major causes of Legg
      Perthes disease. The elevated levels of lipoprotein (a) in children with Legg
      Perthes disease suggest that they may be at risk for atherosclerosis as adults.

PMID- 12208919
TI  - Increased frequency of acute local reaction to intra-articular hylan GF-20
      (synvisc) in patients receiving more than one course of treatment.
AB  - BACKGROUND: Intra-articular knee injections with hylan GF-20 (Synvisc) have been
      shown to provide temporary relief of osteoarthritic symptoms. Several studies
      have suggested that repeated courses of treatment with this product may be
      administered without an increase in the likelihood of an adverse reaction. The
      present study was performed to test the hypothesis that the likelihood of a
      painful reaction to hylan GF-20 does not increase in patients who receive more
      than one course of treatment. METHODS: The records of all patients who had
      received more than one course of treatment with hylan GF-20 were compared with a
      group of patients who had received only one course of treatment during the same
      fifteen-month period at a single center. The single-course group was
      prospectively enrolled and followed, as part of an ongoing randomized trial. The
      two groups were compared with respect to several demographic and clinical
      parameters as well as with respect to the frequency of painful acute local
      reactions following injections of hylan GF-20. RESULTS: Local reactions to hylan
      GF-20 occurred significantly more often in patients who had received more than
      one course of treatment than they did in patients who had received only a single
      course of treatment; the reactions occurred in four (21%) of nineteen patients in
      the former group and in one (2%) of the forty-two patients in the latter (p =
      0.029). All of the reactions were severe enough to cause the patient to seek
      unscheduled care. Following corticosteroid injection, the reactions abated
      without apparent sequelae. With the numbers available, no significant differences
      were detected between the multiple-course and single-course groups in terms of
      age, gender, body-mass index, or severity or bilaterality of the disease.
      CONCLUSIONS: The present study suggests that it may be reasonable to counsel
      patients who have been treated with a course of hylan GF-20 and who desire an
      additional course that the likelihood of a painful acute local reaction to the
      medication appears to be increased. Additional study of the frequency of acute
      local reactions following repeated courses of hylan GF-20 and investigation of
      the mechanisms of those reactions are warranted.

PMID- 12208920
TI  - Rattlesnake bites in children: antivenin treatment and surgical indications.
AB  - BACKGROUND: Orthopaedic surgeons working in the Americas may be consulted in the
      care of patients bitten by venomous rattlesnakes (genus Crotalus ), particularly
      with regard to the possibilities of compartment syndrome and soft-tissue
      destruction. Despite considerable evidence regarding the safety and efficacy of
      antivenin in the treatment of rattlesnake bites in adults, controversy persists
      regarding the roles of antivenin and surgery in the treatment of rattlesnake
      envenomations in children. Our hypothesis is that aggressive use of antivenin is
      just as effective and safe for children as it is for adults. METHODS: We
      retrospectively reviewed the charts of twenty-four consecutive patients who had
      been managed at our hospital because of a bite from a western diamondback
      rattlesnake. Nineteen of the twenty-four patients had been envenomated. The
      uniformity of collected data was facilitated by the use of an intensive-care-unit
      protocol during the ten-year period that was reviewed. A questionnaire was
      developed for long-term follow-up. RESULTS: Aggressive use of polyvalent equine
      antivenin safely prevented the need for surgery in sixteen of the nineteen
      envenomated patients. Of the three patients who had surgical treatment, two were
      managed with limited soft-tissue debridement and one was managed with a
      fasciotomy of the leg because of a compartment syndrome that occurred when
      adequate antivenin was withheld. No serious adverse effects were noted in
      association with the antivenin, and no functional impairments were noted at the
      time of discharge. CONCLUSION: Antivenin, rather than surgery, is the proper
      initial treatment of severe rattlesnake envenomations in children.

PMID- 12208921
TI  - Treatment of unreduced elbow dislocations with hinged external fixation.
AB  - BACKGROUND: The results of operative treatment of an unreduced elbow dislocation
      have been regarded with pessimism. Suggested procedures have included tendon
      lengthening, tendon transfer, or reconstruction of ligament or bone. METHODS:
      Three women and two men (average age, forty-nine years) with an unreduced
      dislocation of the elbow without associated fractures were treated with open
      relocation of the joint and hinged external fixation at an average of eleven
      weeks (range, six to thirty weeks) after the initial injury. The lateral soft
      tissues, including the origin of the lateral collateral ligament complex, were
      reattached to the lateral epicondyle in three patients, but no attempt was made
      to reconstruct the ligaments, tendons, or bone. A passive worm gear incorporated
      into a hinged external fixator was used to mobilize the elbow initially, and
      active mobilization was gradually introduced. The hinge was removed at an average
      of five weeks after the procedure. RESULTS: At an average of thirty-eight months
      (range, twelve to ninety-eight months), a stable, concentric reduction had been
      maintained in all five patients, with radiographic signs of mild arthrosis in
      four. The average arc of flexion was 123 degrees, and all patients had full
      forearm rotation. The average score on the Mayo Elbow Performance Index was 89
      points, with two excellent and three good results. The average scores on the
      Disabilities of the Arm, Shoulder and Hand (DASH) and American Shoulder and Elbow
      Surgeons outcome instruments (13 and 92 points, respectively) reflected mild
      residual pain and disability. CONCLUSIONS: Treatment of unreduced elbow
      dislocations with open reduction and hinged external fixation as much as thirty
      weeks after the injury can restore a stable, mobile joint without the need for
      tendon-lengthening or transfer, ligament reconstruction, or deepening of the
      trochlear notch of the ulna.

PMID- 12208922
TI  - Long-term results of use of a collared matte-finished femoral component fixed
      with second-generation cementing techniques. A fifteen-year-median follow-up
      study.
AB  - BACKGROUND: So-called second-generation cementing techniques in total hip
      arthroplasty have been shown to provide better survival of the femoral component
      than first-generation methods do; however, surface finish and other features of
      the component design also influence the durability of the reconstruction. The
      purpose of this study was to determine the results of primary total hip
      replacement with use of a collared femoral component with a matte-finished
      surface fixed with second-generation cementing techniques and followed for ten to
      twenty years. METHODS: The study group consisted of 256 consecutive hips in 236
      patients who had had a primary total hip arthroplasty with fixation of a Harris
      Design-2 femoral component with second-generation cementing techniques (use of an
      intramedullary plug and a cement gun). The mean age of the patients at the time
      of the operation was sixty-six years. One hundred and twelve patients were male,
      and 124 were female. Seven patients were lost to follow-up less than ten years
      after the operation. The median duration of follow-up of the living patients who
      had not had a revision was 15.4 years. RESULTS: At the time of the most recent
      follow-up, nineteen femoral components (7%) had been revised because of aseptic
      loosening, five (2%) had been removed because of deep infection, and one (0.4%)
      had been revised because of recurrent dislocation. The mean Harris hip score for
      the surviving patients who had not had a revision improved from 51 points
      preoperatively to 91 points at the most recent evaluation. At fifteen years, the
      estimated survival rate of the femoral components was 92.2% with revision due to
      aseptic loosening as the end point and 90.1% with mechanical failure
      (radiographic loosening or revision due to aseptic loosening) as the end point.
      Patients who were younger than fifty years old at the time of the operation had a
      lower fifteen-year rate of survival of the femoral implant, in terms of both
      revision due to aseptic loosening (72.3% compared with 95.7%, p = 0.0001) and
      mechanical failure (72.3% compared with 93.1%, p = 0.005), than did patients who
      were fifty years or older. CONCLUSIONS: Fixation of this collared matte-finished
      femoral component with use of second-generation cementing techniques for primary
      total hip replacement provided satisfactory results at ten to twenty years in
      older patients but less satisfactory results in younger patients.

PMID- 12208923
TI  - Periprosthetic humeral fractures after total elbow arthroplasty: treatment with
      implant revision and strut allograft augmentation.
AB  - BACKGROUND: Periprosthetic fractures are among the most challenging complications
      of elbow arthroplasty, and published information about the outcome of treatment
      is limited. The purpose of the present study was to determine the results of
      implant revision and strut allograft augmentation for the treatment of humeral
      periprosthetic fractures that occur around a loose humeral component. METHODS:
      Between 1991 and 1999, eleven periprosthetic fractures that occurred around a
      loose humeral component were treated with cortical strut allograft augmentation
      and revision arthroplasty with use of a Coonrad-Morrey semiconstrained implant.
      Six fractures occurred after a primary arthroplasty, and five occurred after a
      revision arthroplasty. Two parallel strut grafts were used for fracture fixation
      in most cases. Patients were followed for an average of three years (range, nine
      months to 7.8 years) and were evaluated clinically and radiographically. RESULTS:
      Clinical and radiographic fracture union was obtained in ten of the eleven
      patients. One patient required revision surgery because of aseptic loosening of
      the humeral component seven years and nine months after fracture union; there
      were no other implant failures. Complications included one additional
      nondisplaced humeral periprosthetic fracture after surgery that failed to heal
      with closed treatment, one olecranon fracture, one permanent ulnar nerve injury,
      and one case of triceps insufficiency. At the time of the most recent follow-up,
      seven of the eight patients with an intact reconstruction had a functional arc of
      motion and no or slight pain and one had limited motion and moderate pain.
      CONCLUSIONS: Periprosthetic humeral fractures that are associated with a loose
      humeral component can be effectively treated with revision elbow arthroplasty and
      strut allograft augmentation. The technique is associated with a high rate of
      fracture union, implant survival, and satisfactory clinical results. However, the
      complication rate is substantial.

PMID- 12208924
TI  - Evaluation of a femoral stem with reduced stiffness. A randomized study with use
      of radiostereometry and bone densitometry.
AB  - BACKGROUND: Femoral stems with reduced stiffness were introduced in total hip
      arthroplasty to facilitate proximal load transfer and thereby reduce
      periprosthetic bone loss. Poor fixation and unacceptably high revision rates
      turned out to be a major problem with these prostheses. The purpose of the
      present study was to evaluate the early performance of a low-modulus stem (one
      that is less stiff) with the potential to address the problem of fixation by the
      use of a surface coating. The coating consisted of a titanium porous mesh
      proximally covered with a mixture of hydroxyapatite and tricalcium phosphate.
      METHODS: Thirty-nine men and twenty-six women (sixty-eight hips) with
      noninflammatory arthritis were studied. The patients were randomized to receive
      either a porous-coated composite stem with reduced stiffness (Epoch) or a stiff
      stem with a porous coating (Anatomic). Both stems were inserted without cement,
      had a ceramic coating on the proximal two-thirds, and were supplied with tantalum
      beads. At the time of the operation, tantalum markers were also placed into the
      proximal part of the femur. The patients were followed for up to two years after
      the operation and were evaluated with use of repeated radiostereometric
      measurements, measurements of bone-mineral density, conventional radiography, and
      Harris hip scores. RESULTS: Both stems showed optimum fixation with median
      subsidence and stem rotations that were close to zero. Repeated measurements of
      bone-mineral density revealed early loss of bone mineral in all Gruen regions in
      both treatment groups. The loss of bone mineral around the Epoch stems was
      significantly reduced at two years in Gruen regions 1, 2, 6, and 7 (p < 0.0005 to
      0.04). Measurements on postoperative radiographs showed no difference in stem
      positioning or fill, but the Epoch stems had significantly more endocortical
      contact on both the anteroposterior (p < 0.0005) and the lateral radiograph (p =
      0.02). At two years postoperatively, the Epoch stems had fewer sclerotic lines
      surrounding the stem (p = 0.002) and less sclerosis at the tip of the prosthesis
      (p = 0.001) compared with the Anatomic stems. The clinical results in terms of
      the Harris hip score, which was determined in all hips, and pain or discomfort,
      which was evaluated in thirty-seven hips treated at the same hospital, were not
      found to be different, with the numbers available. CONCLUSIONS: Contrary to
      previous studies of other designs with reduced stiffness, the Epoch stem achieved
      excellent primary fixation. Despite this rigid fixation, the proximal loss of
      bone-mineral density was less than that associated with the stem with a stiffer
      design. These results should encourage additional long-term studies with a larger
      patient population.

PMID- 12208925
TI  - Intermittent occlusion of the popliteal vein by a gastrocnemius rotational muscle
      flap. A report of two cases.

PMID- 12208926
TI  - Giant-cell tumor of the tendon sheath involving the cervical spine. A case
      report.

PMID- 12208927
TI  - Management of capsular deficiency of the shoulder. A report of three cases.

PMID- 12208928
TI  - User's guide to the orthopaedic literature: how to use a systematic literature
      review.

PMID- 12208931
TI  - Diagnostic tests for tarsal tunnel syndrome.

PMID- 12208930
TI  - The challenges of change: is orthopaedics ready?

PMID- 12208932
TI  - Evaluating external spinal skeletal fixation used predictively to select
      candidates for lumbar arthrodesis: nonfixation controls.

PMID- 12208933
TI  - Association between hospital and surgeon procedure volume and outcomes of
      orthopaedic surgery: caveats for interpretation of data and policy applications.

PMID- 12208934
TI  - Flexor tenosynovectomy in the treatment of carpal tunnel syndrome: some
      theoretical and procedural differences.

PMID- 12208935
TI  - What's new in adult reconstructive knee surgery.

PMID- 12208936
TI  - Secondary structure and hybridization accessibility of hepatitis C virus 3'
      terminal sequences.
AB  - The 3'-terminal sequences of hepatitis C virus (HCV) positive- and negative
      strand RNAs contribute cis-acting functions essential for viral replication. The
      secondary structure and protein-binding properties of these highly conserved
      regions are of interest not only for the further elucidation of HCV molecular
      biology, but also for the design of antisense therapeutic constructs. The RNA
      structure of the positive-strand 3' untranslated region has been shown previously
      to influence binding by various host and viral proteins and is thus thought to
      promote HCV RNA synthesis and genome stability. Recent studies have attributed
      analogous functions to the negative-strand 3' terminus. We evaluated the HCV
      negative-strand secondary structure by enzymatic probing with single-strand
      specific RNases and thermodynamic modeling of RNA folding. The accessibility of
      both 3'-terminal sequences to hybridization by antisense constructs was evaluated
      by RNase H cleavage mapping in the presence of combinatorial oligodeoxynucleotide
      libraries. The mapping results facilitated identification of antisense
      oligodeoxynucleotides and a 10-23 deoxyribozyme active against the positive
      strand 3'-X region RNA in vitro.

PMID- 12208937
TI  - Vaccinia virus J1R protein: a viral membrane protein that is essential for virion
      morphogenesis.
AB  - Vaccinia virus, a member of the poxvirus family, contains a conserved J1R open
      reading frame that encodes a late protein of 17.8 kDa. The 18-kDa J1R protein is
      associated mainly with the membrane fraction of intracellular mature virus
      particles. This study examines the biological function of J1R protein in the
      vaccinia virus life cycle. A recombinant vaccinia virus was constructed to
      conditionally express J1R protein in an isopropyl-beta-D-galactopyranoside (IPTG)
      inducible manner. When J1R is not expressed during vaccinia virus infection, the
      virus titer is reduced approximately 100-fold. In contrast, J1R protein is not
      required for viral gene expression, as indicated by protein pulse-labeling. J1R
      protein is also not required for DNA processing, as the resolution of the
      concatemer junctions of replicated viral DNA was detected without IPTG. A
      deficiency of J1R protein caused a severe delay in the processing of p4a and p4b
      into mature core proteins 4a and 4b, indicating that J1R protein participates in
      virion morphogenesis. Infected cells grown in the absence of IPTG contained very
      few intracellular mature virions in the cytoplasm, and enlarged viroplasm
      structures accumulated with viral crescents attached at the periphery. Abundant
      intermediate membrane structures of abnormal shapes were observed, and many
      immature virions were either empty or partially filled, indicating that J1R
      protein is important for DNA packaging into immature virions. J1R protein also
      coimmunoprecipited with A45R protein in infected cells. In summary, these results
      indicate that vaccinia virus J1R is a membrane protein that is required for virus
      growth and plaque formation. J1R protein interacts with A45R protein and performs
      an important role during immature virion formation in cultured cells.

PMID- 12208938
TI  - Replication of a cytopathic strain of bovine viral diarrhea virus activates PERK
      and induces endoplasmic reticulum stress-mediated apoptosis of MDBK cells.
AB  - Endoplasmic reticulum (ER) stress signaling is an adaptive cellular response to
      the loss of ER Ca(2+) homeostasis and/or the accumulation of misfolded,
      unassembled, or aggregated proteins in the ER lumen. ER stress-activated
      signaling pathways regulate protein synthesis initiation and can also trigger
      apoptosis through the ER-associated caspase 12. Viruses that utilize the host
      cell ER as an integral part of their life cycle would be predicted to cause some
      level of ER stress. Bovine viral diarrhea virus (BVDV) is a positive-stranded RNA
      virus of the Flaviviridae family. BVDV and related flaviviruses use the host ER
      as the primary site of envelope glycoprotein biogenesis, genomic replication, and
      particle assembly. We are using a cytopathic strain of BVDV (cpBVDV) that causes
      cellular apoptosis as a model system to determine how virus-induced ER stress
      contributes to pathogenesis. We show that, in a natural infection of MDBK cells,
      cpBVDV activates the ER transmembrane kinase PERK (PKR-like ER kinase) and causes
      hyperphosphorylation of the translation initiation factor eIF2 alpha, consistent
      with the induction of an ER stress response. Additionally, we show that
      initiation of cellular apoptosis correlates with downregulation of the
      antiapoptotic Bcl-2 protein, induced expression of caspase 12, and a decrease in
      intracellular glutathione levels. Defining the molecular stress pathways leading
      to cpBVDV-induced apoptosis provides the basis to study how other ER-tropic
      viruses, such as hepatitis C and B viruses, modulate the host cell ER stress
      response during the course of persistent infection.

PMID- 12208940
TI  - Intramolecular recombinations of Moloney murine leukemia virus occur during minus
      strand DNA synthesis.
AB  - Retroviral recombination can occur between two viral RNA molecules
      (intermolecular) or between two sequences within the same RNA molecule
      (intramolecular). The rate of retroviral intramolecular recombination is high.
      Previous studies showed that, after a single round of replication, 50 to 60% of
      retroviral recombinations occur between two identical sequences within a Moloney
      murine leukemia virus-based vector. Recombination can occur at any polymerization
      step within the retroviral replication cycle. Although reverse transcriptase is
      assumed to contribute to the template switches, previous studies could not
      distinguish between changes introduced by host RNA polymerase II (Pol II) or by
      reverse transcriptase. A cell culture system has been established to detect the
      individual contribution of host RNA Pol II, host DNA polymerase or viral reverse
      transcriptase, as well as the recombination events taking place during minus
      strand DNA synthesis and plus-strand DNA synthesis in a single round of viral
      intramolecular replication. Studies in this report demonstrate that
      intramolecular recombination between two identical sequences during transcription
      by host RNA Pol II is minimal and that most recombinations occur during minus
      strand DNA synthesis catalyzed by viral reverse transcriptase.

PMID- 12208939
TI  - In vitro intersubtype recombinants of human immunodeficiency virus type 1:
      comparison to recent and circulating in vivo recombinant forms.
AB  - The increased prevalence of human immunodeficiency virus type 1 (HIV-1)
      intersubtype recombinants (ISRs) is shaping HIV-1 evolution throughout the world
      and will have an impact on both therapeutic and vaccine strategies. This study
      was designed to generate and compare in vitro ISRs to those isolated from HIV
      infected individuals throughout the world. Human peripheral blood mononuclear
      cells were dually infected with seven pairs of HIV-1 isolates from different
      subtypes (i.e., A to F). Recombinant crossover sites were mapped to specific
      regions in the envelope (env) gene by using a cloning-hybridization technique and
      subtype-specific probes. In vitro intersubtype recombination was at least twofold
      more frequent in the V1-to-V3 region than in any other env fragment, i.e., C1 to
      V1, V3 to V5, or V5 to gp41. Sequence and recombination site analyses suggested
      the C2 env domain as a "hot region" for recombination and selection of
      replication-competent ISRs during the 15-day incubation. In addition to these
      regional preferences for env recombination, homopolymeric nucleotide tracts,
      i.e., sequences known to pause reverse transcriptase and promote template
      switching, were found in most in vitro crossover sites. ISRs, originating from
      recent dual infections and limited transmission events, partly retained this in
      vitro regional or sequence preference for recombination sites. However, a shift
      to crossover sites flanking the gp120-coding sequence was evident in the stable
      circulating recombinant forms of HIV-1. Based on these findings, HIV-1
      recombinants generated from these dual infections may be used as a model for in
      vivo intersubtype recombination and for the design of various diagnostic assays
      and vaccine constructs.

PMID- 12208941
TI  - Feline immunodeficiency virus OrfA is distinct from other lentivirus
      transactivators.
AB  - The feline immunodeficiency virus (FIV) accessory factor, OrfA, facilitates
      transactivation of transcription directed by elements of the viral long terminal
      repeat (LTR). In order to map OrfA domains required for this transactivation, we
      used N- and C-terminal deletion constructs of the protein, expressed in a Gal4
      based transactivation system. The results demonstrated that FIV OrfA, unlike
      other lentiviral transactivators such as visna virus Tat, is unable to
      transactivate from minimal promoter-based reporters and requires additional
      elements of the viral LTR. Stable CrFK-based cell lines were prepared that
      expressed OrfA to readily detectable levels and in which we were able to
      demonstrate 32-fold transactivation of an LTR-chloramphenicol acetyltransferase
      construct. Transactivation was heavily dependent on the presence of an ATF site
      within the viral LTR. Changing the translation initiation codon context
      substantially increased the level of production of OrfA from a bicistronic
      message that also encodes Rev. In the presence of a more favorable context
      sequence, the upstream expression of OrfA increased 21-fold, with only a 0.5-fold
      drop in downstream Rev expression. This suggests that Rev translation may occur
      via an internal ribosomal entry site rather than by leaky scanning.

PMID- 12208942
TI  - Epstein-Barr virus mRNA export factor EB2 is essential for production of
      infectious virus.
AB  - The splicing machinery which positions a protein export complex near the exon
      exon junction mediates nuclear export of mRNAs generated from intron-containing
      genes. Many Epstein-Barr virus (EBV) early and late genes are intronless, and an
      alternative pathway, independent of splicing, must export the corresponding
      mRNAs. Since the EBV EB2 protein induces the cytoplasmic accumulation of
      intronless mRNA, it is tempting to speculate that EB2 is a viral adapter involved
      in the export of intronless viral mRNA. If this is true, then the EB2 protein is
      essential for the production of EBV infectious virions. To test this hypothesis,
      we generated an EBV mutant in which the BMLF1 gene, encoding the EB2 protein, has
      been deleted (EBV(BMLF1-KO)). Our studies show that EB2 is necessary for the
      production of infectious EBV and that its function cannot be transcomplemented by
      a cellular factor. In the EBV(BMLF1-KO) 293 cells, oriLyt-dependent DNA
      replication was greatly enhanced by EB2. Accordingly, EB2 induced the cytoplasmic
      accumulation of a subset of EBV early mRNAs coding for essential proteins
      implicated in EBV DNA replication during the productive cycle. Two herpesvirus
      homologs of the EB2 protein, the herpes simplex virus type 1 protein ICP27 and,
      the human cytomegalovirus protein UL69, only partly rescued the phenotype of the
      EBV(BMLF1-KO) mutant, indicating that some EB2 functions in virus production
      cannot be transcomplemented by ICP27 and UL69.

PMID- 12208943
TI  - Identification of Epstein-Barr virus strain variants in hairy leukoplakia and
      peripheral blood by use of a heteroduplex tracking assay.
AB  - Epstein-Barr virus (EBV) strains can be distinguished by specific sequence
      variations in the LMP1 gene. In this study, a heteroduplex tracking assay (HTA)
      specific for LMP1 was developed to precisely identify the prototypic undeleted
      strain B958, other undeleted strains (Ch2, AL, NC, and Med-), and strains with
      the 30-bp deletion (Med+ and Ch1). This technique also provides an estimate of
      the relative abundance of strains in patient samples. In this study, EBV strains
      were identified in 25 hairy leukoplakia (HLP) biopsies and six matched peripheral
      blood samples and throat washes with the LMP1-HTA. To investigate the
      relationship of the virus found in the peripheral blood to that in the HLP
      lesion, the strain variants in the peripheral blood B lymphocytes and those
      present within the epithelial cells in the HLP lesion and in throat washes were
      identified. In many of the subjects, compartmental differences in the EBV strain
      profiles in the oral cavity and peripheral blood were readily apparent. The
      throat wash specimens usually had a strain profile similar to that within the
      corresponding HLP sample, which was distinct from the strain profile detected in
      the peripheral blood. These analyses reveal that the nature of EBV infection can
      be very dynamic, with changes in relative strain abundance over time as well as
      the appearance of new strains. The patterns of abundance in the blood and oral
      cavity provide evidence for compartmentalization and for the transmission of
      strains between the blood and oropharynx.

PMID- 12208944
TI  - Susceptibility to polyomavirus-induced tumors in inbred mice: role of innate
      immune responses.
AB  - Mice of the PERA/Ei strain (PE mice) are highly susceptible to tumor induction by
      polyomavirus and transmit their susceptibility in a dominant manner in crosses
      with resistant C57BR/cdJ mice (BR mice). BR mice respond to polyomavirus
      infection with a type 1 cytokine response and develop effective cell-mediated
      immunity to the virus-induced tumors. By enumerating virus-specific CD8(+) T
      cells and measuring cytokine responses, we show that the susceptibility of PE
      mice is due to the absence of a type 1 cytokine response and a concomitant
      failure to sustain virus-specific cytotoxic T lymphocytes. (PE x BR)F(1) mice
      showed an initial type 1 response that became skewed toward type 2. Culture
      supernatants of splenocytes from infected PE mice stimulated in vitro contained
      high levels of interleukin-10 and no detectable gamma interferon, while those
      from BR mice showed the opposite pattern. Differences in the innate immune
      response to polyomavirus by antigen-presenting cells in PE mice and BR mice led
      to polarization of T-cell cytokine responses. Adherent cells from spleens of
      infected BR mice produced high levels of interleukin-12, while those from
      infected PE and F(1) mice produced predominantly interleukin-10. PE and F(1) mice
      infected by polyomavirus responded with increases in antigen-presenting cells
      expressing B7.2 costimulatory molecules, whereas BR mice responded with increased
      expression of B7.1. Administration of recombinant interleukin-12 along with virus
      resulted in partial protection of PE mice and provided complete protection
      against tumor development in F(1) animals.

PMID- 12208945
TI  - The mengovirus leader protein suppresses alpha/beta interferon production by
      inhibition of the iron/ferritin-mediated activation of NF-kappa B.
AB  - In our studies on the biological function of the mengovirus leader protein, we
      identified a casein kinase II (CK-2) phosphorylation site in the protein. Here we
      report that the mengovirus leader protein can be phosphorylated by CK-2 in vitro.
      Expression of a recombinant leader protein in which the consensus CK-2 sequence
      around threonine 47 was disturbed resulted in a mutant protein that could no
      longer be phosphorylated. The CK-2 consensus sequence was modified by site
      directed mutagenesis and subsequently introduced into a mengovirus cDNA clone to
      investigate the effect of the phosphorylation of the leader protein on virus
      replication and on the host cell response. Modifications by which the CK-2
      consensus sequence was disturbed resulted in mutant viruses with reduced growth
      kinetics. We demonstrated that the integrity of the CK-2 phosphorylation site of
      the mengovirus leader protein was specifically related to the suppression of NF
      kappa B activation and subsequent suppression of alpha/beta interferon production
      in infected cells. We also found that the integrity of the CK-2 phosphorylation
      site of the leader protein coincided with an increase of ferritin expression in
      the infected cell. These data indicate that the leader protein suppresses the
      iron-mediated activation of NF-kappa B and thereby inhibits alpha/beta interferon
      expression in the infected cell.

PMID- 12208946
TI  - Relationship between SU subdomains that regulate the receptor-mediated transition
      from the native (fusion-inhibited) to the fusion-active conformation of the
      murine leukemia virus glycoprotein.
AB  - Envelope glycoproteins (Env) of retroviruses are trimers of SU (surface) and TM
      (transmembrane) heterodimers and are expressed on virions in fusion-competent
      forms that are likely to be metastable. Activation of the viral receptor-binding
      domain (RBD) via its interaction with a cell surface receptor is thought to
      initiate a cascade of events that lead to refolding of the Env glycoprotein into
      its stable fusion-active conformation. While the fusion-active conformation of
      the TM subunit has been described in detail for several retroviruses, little is
      known about the fusion-competent structure of the retroviral glycoproteins or the
      molecular events that mediate the transition between the two conformations. By
      characterizing Env chimeras between the ecotropic and amphotropic murine leukemia
      virus (MLV) SUs as well as a set of point mutants, we show that alterations of
      the conformation of the SU glycoprotein strongly elevate Env fusogenicity by
      disrupting the stability of the Env complex. Compensatory mutations that restored
      both Env stability and fusion control were also identified, allowing definition
      of interactions within the Env complex that maintain the stability of the native
      Env complex. We show that, in the receptor-unbound form, structural interactions
      between the N terminus of the viral RBD (NTR domain), the proline-rich region
      (PRR), and the distal part of the C-terminal domain of the SU subunit maintain a
      conformation of the glycoprotein that is fusion inhibitory. Additionally, we
      identified mutations that disrupt this fusion-inhibitory conformation and allow
      fusion activation in the absence of viral receptors, provided that receptor
      activated RBD fragments are added in trans during infection. Other mutations were
      identified that allow fusion activation in the absence of receptors for both the
      viral glycoprotein and the trans-acting RBD. Finally, we found mutations of the
      SU that bypass in cis the requirement for the NTR domain in fusion activation.
      All these different mutations call for a critical role of the PRR in mediating
      conformational changes of the Env glycoprotein during fusion activation. Our
      results suggest a model of MLV Env fusion activation in which unlocking of the
      fusion-inhibitory conformation is initiated by receptor binding of the viral RBD,
      which, upon disruption of the PRR, allows the NTR domain to promote further
      events in Env fusion activation. This involves a second type of interaction, in
      cis or in trans, between the receptor-activated RBD and a median segment of the
      freed C-terminal domain.

PMID- 12208947
TI  - Identification and characterization of a cis-acting replication element (cre)
      adjacent to the internal ribosome entry site of foot-and-mouth disease virus.
AB  - Over the last few years, an essential RNA structure known as the cis-acting
      replicative element (cre) has been identified within the protein-coding region of
      several picornaviruses. The cre, a stem-loop structure containing a conserved
      AAACA motif, functions as a template for addition of U residues to the protein
      primer 3B. By surveying the genomes of representatives of several serotypes of
      foot-and-mouth disease virus (FMDV), we discovered a putative cre in the 5'
      untranslated region of the genome (contiguous with the internal ribosome entry
      site [IRES]). To confirm the role of this putative cre in replication, we tested
      the importance of the AAACA motif and base pairing in the stem in FMDV genome
      replication. To this end, cre mutations were cloned into an FMDV replicon and
      into synthetic viral genomes. Analyses of the properties of these replicons and
      genomes revealed the following. (i) Mutations in the AAACA motif severely reduced
      replication, and all viruses recovered from genomes containing mutated AAACA
      sequences had reverted to the wild-type sequence. (ii) Mutations in the stem
      region showed that the ability to form this base-paired structure was important
      for replication. Although the cre was contiguous with the IRES, the mutations we
      created did not significantly reduce IRES-mediated translation in vivo. Finally,
      the position of the cre at the 5' end of the genome was shown not to be critical
      for replication, since functional replicons and viruses lacking the 5' cre could
      be obtained if a wild-type cre was added to the genome following the 3D(pol)
      coding region. Taken together, these results support the importance of the cre in
      replication and demonstrate that the activity of this essential element does not
      require localization within the polyprotein-encoding region of the genome.

PMID- 12208948
TI  - Phylogenetic and functional analysis of the bacteriophage P1 single-stranded DNA
      binding protein.
AB  - Bacteriophage P1 encodes a single-stranded DNA-binding protein (SSB-P1), which
      shows 66% amino acid sequence identity to the SSB protein of the host bacterium
      Escherichia coli. A phylogenetic analysis indicated that the P1 ssb gene coexists
      with its E. coli counterpart as an independent unit and does not represent a
      recent acquisition of the phage. The P1 and E. coli SSB proteins are fully
      functionally interchangeable. SSB-P1 is nonessential for phage growth in an
      exponentially growing E. coli host, and it is sufficient to promote bacterial
      growth in the absence of the E. coli SSB protein. Expression studies showed that
      the P1 ssb gene is transcribed only, in an rpoS-independent fashion, during
      stationary-phase growth in E. coli. Mixed infection experiments demonstrated that
      a wild-type phage has a selective advantage over an ssb-null mutant when exposed
      to a bacterial host in the stationary phase. These results reconciled the
      observed evolutionary conservation with the seemingly redundant presence of ssb
      genes in many bacteriophages and conjugative plasmids.

PMID- 12208949
TI  - The upstream regulatory region of human papillomavirus type 31 is insensitive to
      glucocorticoid induction.
AB  - The upstream regulatory region (URR) of various types of human papillomaviruses
      (HPVs) has been shown to contain functional glucocorticoid response elements
      (GREs), including HPV type 11 (HPV11), HPV16, and HPV18. Glucocorticoids have
      been demonstrated to induce the transcriptional activity of the early promoters
      of these HPV types. Although it has been assumed that the URR of HPV31 contains
      at least one GRE, no functionality has been demonstrated. We attempt to show here
      inducibility of the URR of HPV31 by the synthetic glucocorticoid dexamethasone
      (dex). By sequence analysis we identified three potential GREs in the URR of
      HPV31. Gel shift analysis indicated that each of these three sites has the
      potential to be a functional GRE. However, constructs containing the full-length
      URR, 5' deletions of the URR, and an internal fragment of the URR containing all
      three putative GREs were only weakly inducible by dex. Linker scanning mutants,
      whereby each potential GRE was replaced individually, in double combination, or
      in triple combination by a unique polylinker, had no effect on dex inducibility.
      Replacement of each of the three HPV31 GREs with the GRE of HPV18 failed to
      induce a response to dex. Placement of the HPV18 GRE into the URR of HPV31 in a
      region similar to its location in the HPV18 URR was also unable to result in a
      strong dex induction of the HPV31 URR. These data suggest that the lack of dex
      inducibility is due to the overall context of the HPV31 URR and may be dependent
      on the requirements of the major early promoter for transcriptional activation.
      Finally, replacement of the HPV18 GRE with each of the HPV31 GREs in HPV18 only
      showed weak inducibility, indicating that the three GREs of HPV31 are in fact
      only weak inducers of dex. Overall, these data suggest that dex responsiveness,
      along with oncogenic potential, may provide a possible explanation for the
      classification of HPV31 as an intermediate-risk virus and demonstrate the
      complexity of transcriptional regulation of the URR of HPV.

PMID- 12208950
TI  - The adenovirus E3 RID complex protects some cultured human T and B lymphocytes
      from Fas-induced apoptosis.
AB  - Human group C adenoviruses cause an acute infection in respiratory epithelia and
      establish a long-term or persistent infection, possibly in lymphocytes. The
      mechanism by which this persistence is maintained is unknown; however, it would
      require that persistently infected lymphocytes not be deleted. The adenovirus
      genome encodes proteins that prevent the immune system from eliminating the virus
      infected cell, including the E3 receptor internalization and degradation (RID)
      complex. The RID complex prevents death of infected cells by blocking apoptosis
      initiated through death domain-containing receptors of the tumor necrosis factor
      receptor (TNFR) superfamily, including TNFR1 (L. R. Gooding, T. S. Ranheim, A. E.
      Tollefson, L. Aquino, P. Duerksen-Hughes, T. M. Horton, and W. S. Wold, J. Virol.
      65:4114-4123, 1991), TNF-related apoptosis-inducing ligand receptors (TRAIL-R1
      and -R2) (C. A. Benedict, P. S. Norris, T. I. Prigozy, J. L. Bodmer, J. A. Mahr,
      C. T. Garnett, F. Martinon, J. Tschopp, L. R. Gooding, and C. F. Ware, J. Biol.
      Chem. 276:3270-3278, 2001; A. E. Tollefson, K. Toth, K. Doronin, M. Kuppuswamy,
      O. A. Doronina, D. L. Lichtenstein, T. W. Hermiston, C. A. Smith, and W. S. Wold,
      J. Virol. 75:8875-8887, 2001), and Fas (J. Shisler, C. Yang, B. Walter, C. F.
      Ware, and L. R. Gooding, J. Virol. 71:8299-8306, 1997). Here, we test the ability
      of RID to protect human lymphocytes from apoptosis induced by ligation of Fas, a
      mechanism important for regulating lymphocyte populations. Using a retrovirus
      expressing RID to infect six human lymphocyte cell lines, we found that RID
      functions in the absence of other viral proteins to downregulate surface Fas on
      some, but not all, cell lines. Total cellular levels of Fas decrease as measured
      by Western blotting, and this loss of Fas correlates with protection from
      apoptosis induced by ligation of Fas in every cell line tested. Although in some
      cases, RID causes loss of only a fraction of surface Fas, the presence of RID
      completely blocks the immediate events downstream of Fas ligation (i.e., Fas-FADD
      association and caspase-8 cleavage) in susceptible cell lines. Nonetheless, the
      ability of RID to block Fas signaling is independent of the Fas signaling pathway
      used (type I or type II). Interestingly, among the four T-cell lines tested, RID
      caused loss of Fas in the two T-cell lines bearing a relatively immature
      phenotype, while having no activity in T cells with mature phenotypes.
      Collectively, these data suggest that RID functions to prevent apoptosis of some
      human lymphocytes by internalizing surface Fas receptors. It is possible that the
      expression of RID facilitates long-term infection by preventing Fas-mediated
      deletion of persistently infected lymphocytes.

PMID- 12208951
TI  - Human immunodeficiency virus type 1 (HIV-1) accessory protein Vpr induces
      transcription of the HIV-1 and glucocorticoid-responsive promoters by binding
      directly to p300/CBP coactivators.
AB  - The accessory Vpr protein of human immunodeficiency virus type 1 (HIV-1) is a
      promiscuous activator of viral and cellular promoters. We report that Vpr
      enhances expression of the glucocorticoid receptor-induced mouse mammary tumor
      virus (MMTV) promoter and of the Tat-induced HIV-1 long terminal repeat promoter
      by directly binding to p300/CBP coactivators. In contrast, Vpr does not bind to
      p/CAF or to members of the p160 family of nuclear receptor coactivators, such as
      steroid receptor coactivator 1a and glucocorticoid receptor (GR)-interacting
      protein 1. Vpr forms a stable complex with p300 and also interacts with the
      ligand-bound glucocorticoid receptor in vivo. Mutation analysis showed that the C
      terminal part of Vpr binds to the C-terminal portion of p300/CBP within amino
      acids 2045 to 2191. The same p300 region interacts with the p160 coactivators and
      with the adenovirus E1A protein. Accordingly, E1A competed for binding to p300 in
      vitro. Coexpression of E1A or of small fragments of p300 containing the Vpr
      binding site resulted in inhibition of Vpr's transcriptional effects. The C
      terminal part of p300 containing the transactivating region is required for Vpr
      transactivation, whereas the histone acetyltransferase enzymatic region is
      dispensable. Vpr mutants that bind p300 but not the GR did not activate
      expression of the MMTV promoter and had dominant-negative effects. These results
      indicate that Vpr activates transcription by acting as an adapter linking
      transcription components and coactivators.

PMID- 12208952
TI  - Persistence of Borna disease virus in naturally infected sheep.
AB  - To get an insight into Borna disease virus (BDV) epidemiology, an isolated flock
      of approximately 25 sheep within the region of Southeast Germany to which the
      disease is endemic was investigated over a 3-year observation period. BDV
      specific antibodies and RNA in peripheral blood mononuclear cells were detected
      in 12.5 (year 1), 11.5 (year 2), and 19.4% (year 3) and 1.6 (year 1), 0 (year 2),
      and 14.9% (year 3) of the animals, respectively. BDV persisted in asymptomatic
      sheep for up to 2 years. Significantly higher numbers of antibody-positive
      animals were detected seasonally in spring and early summer, the times when
      usually most of the clinical cases of Borna disease occur. In spring of the third
      year, numbers of antibody-positive and viral-RNA-positive animals increased
      significantly despite their having no obvious clinical symptoms. The removal of
      all antibody- and RNA-positive animals from the flock did not reduce the
      prevalence of BDV infections in the following year. During a 3-month observation
      period of three antibody-positive animals, viral RNA was repeatedly detected by
      reverse transcription-PCR in nasal secretions, saliva, and conjunctival fluids.
      Sequence analysis revealed clustered nucleotide exchanges among sheep BDV p24
      genomes, which differed at five positions from the clustered nucleotide exchanges
      seen in horse BDV p24 genomes.

PMID- 12208953
TI  - An early regulatory function required in a cell type-dependent manner is
      expressed by the genomic but not the cDNA copy of the herpes simplex virus 1 gene
      encoding infected cell protein 0.
AB  - The alpha 0 genes of herpes simplex virus 1 (HSV-1) contain three exons. Earlier
      studies have shown that the substitution of genomic sequences with a cDNA copy
      does not alter the capacity of the virus to replicate or establish latent
      infection. Other studies have demonstrated that HSV-1 may express alternatively
      spliced forms of alpha 0 transcripts. The studies reported here centered on a
      mutant HSV-1(vCPc0) strain in which the genomic copies of the alpha 0 gene were
      replaced with cDNA copies. From our research, we report the following
      observations. (i) In contrast to events transpiring in cells infected with wild
      type virus, the expression of HSV-1(vCPc0) genes was delayed or restricted to
      alpha genes for many hours in rabbit skin cells and to a lesser extent in HEp-2
      cells but not in Vero cells. This delay in the expression of HSV-1(vCPc0) beta or
      gamma genes was also multiplicity of infection dependent. (ii) Exposure to MG132,
      a proteasomal inhibitor, before infection with wild-type virus had no significant
      effect on the accumulation of viral proteins in Vero cells and caused an only
      slight delay in viral gene expression in rabbit skin cells in a multiplicity of
      infection-dependent fashion. The drug had no effect when it was added to the
      medium 3 h after infection. (iii) Rabbit skin or HEp-2 cells exposed to MG132 3 h
      after infection with the HSV-1(vCPc0) mutant accumulated only alpha proteins.
      This restriction was cell type dependent but not multiplicity of infection
      dependent. (iv) Both the delay in the expression of beta and gamma genes and the
      effect of MG132 added to the medium 3 h after infection were rescued by
      restoration of the intron 1 sequences in the HSV-1(vCPc0) mutant. However, cells
      transduced by baculoviruses expressing intron 1 RNA did not complement the HSV
      1(vCPc0) mutant, suggesting that the function of intron 1 is in cis rather than
      in trans. We came to the following conclusions as a result. (i) Post-alpha gene
      expression requires the involvement of the proteasomal pathway in a cell type
      dependent manner. Consistent with this requirement, the proapoptotic functions of
      MG132 are blocked in cells infected before exposure to the drug but not after
      exposure. (ii) A function encoded by the alpha 0 gene that is absent from the
      cDNA copy is required for viral gene expression in a cell type- and multiplicity
      of infection-dependent fashion. The absence of this master function delays but
      does not ultimately block viral gene expression in the cell lines tested here.

PMID- 12208954
TI  - A conserved capsid protein surface domain of Cucumber mosaic virus is essential
      for efficient aphid vector transmission.
AB  - A prominent feature on the surfaces of virions of Cucumber mosaic virus (CMV) is
      a negatively charged loop structure (the beta H-beta I loop). Six of 8 amino
      acids in this capsid protein loop are highly conserved among strains of CMV and
      other cucumoviruses. Five of these amino acids were individually changed to
      alanine or lysine (an amino acid of opposite charge) to create nine mutants (the
      D191A, D191K, D192A, D192K, L194A, E195A, E195K, D197A, and D197K mutants).
      Transcripts of cDNA clones were infectious when they were mechanically inoculated
      onto tobacco, giving rise to symptoms of a mottle-mosaic typical of the wild-type
      virus (the D191A, D191K, D192A, E195A, E195K, and D197A mutants), a systemic
      necrosis (the D192K mutant), or an atypical chlorosis with necrotic flecking (the
      L194A mutant). The mutants formed virions and accumulated to wild-type levels,
      but eight of the nine mutants were defective in aphid vector transmission. The
      aspartate-to-lysine mutation at position 197 interfered with infection; the only
      recovered progeny (the D197K(*) mutant) harbored a second-site mutation (denoted
      by the asterisk) of alanine to glutamate at position 193, a proximal site in the
      beta H-beta I loop. Since the disruption of charged amino acid residues in the
      beta H-beta I loop reduces or eliminates vector transmissibility without grossly
      affecting infectivity or virion formation, we hypothesize that this sequence or
      structure has been conserved to facilitate aphid vector transmission.

PMID- 12208956
TI  - The Vaccinia virus E8R gene product: a viral membrane protein that is made early
      in infection and packaged into the virions' core.
AB  - Vaccinia virus (VV), a member of the poxvirus family, is unique among most other
      DNA viruses in that both transcription and DNA replication occur in the cytoplasm
      of the host cell. It was recently shown by electron microscopy (EM) that soon
      after viral DNA synthesis is initiated in HeLa cells, the replication sites
      become enwrapped by the membrane of the endoplasmic reticulum (ER). In the same
      study, a novel VV membrane protein, the E8R gene product, that may play a role in
      the ER wrapping process was identified (N. Tolonen, L. Doglio, S. Schleich, and
      J. Krijnse Locker, Mol. Biol. Cell 12:2031-2046, 2001). In the present study, the
      gene product of E8R was characterized both biochemically and morphologically. We
      show that E8R is made predominantly early in infection but is packaged into the
      virion. On two-dimensional gel electrophoresis, the protein appeared as a single
      spot throughout the VV life cycle; however, in the assembled virion, the protein
      underwent several modifications which resulted in a change in its molecular
      weight and its isoelectric point. EM of labeled cryosections of infected HeLa
      cells showed that the protein localized to the ER and to membranes located on one
      side of the Golgi complex as early as 1 h postinfection. Late in infection, E8R
      was additionally associated with membranes of immature virions and with
      intracellular mature viruses. Although E8R is predominantly associated with
      membranes, we show that the protein is associated with viral cores; the protein
      is present in cores made with NP-40-dithiothreitol as well as in incoming cores,
      the result of the viral entry process, early in infection. Finally, we show that
      E8R can be phosphorylated in vitro by the viral kinase F10L. It is able to bind
      DNA in vitro, and this binding may be modulated by phosphorylation by F10L. A
      putative role of the E8R gene product throughout the VV life cycle is discussed.

PMID- 12208955
TI  - Hepatitis B virus X protein activates the p38 mitogen-activated protein kinase
      pathway in dedifferentiated hepatocytes.
AB  - Hepatitis B virus X protein (pX) is implicated in hepatocarcinogenesis by an
      unknown mechanism. Employing a cellular model linked to pX-mediated
      transformation, we investigated the role of the previously reported Stat3
      activation by pX in hepatocyte transformation. Our model is composed of a
      differentiated hepatocyte (AML12) 3pX-1 cell line that undergoes pX-dependent
      transformation and a dedifferentiated hepatocyte (AML12) 4pX-1 cell line that
      does not exhibit transformation by pX. We report that pX-dependent Stat3
      activation occurs only in non-pX-transforming 4pX-1 cells and conclude that Stat3
      activation is not linked to pX-mediated transformation. Maximum Stat3
      transactivation requires Ser727 phosphorylation, mediated by mitogenic pathway
      activation. Employing dominant negative mutants and inhibitors of mitogenic
      pathways, we demonstrate that maximum, pX-dependent Stat3 transactivation is
      inhibited by the p38 mitogen-activated protein kinase (MAPK)-specific inhibitor
      SB 203580. Using transient-transreporter and in vitro kinase assays, we
      demonstrate for the first time that pX activates the p38 MAPK pathway only in 4pX
      1 cells. pX-mediated Stat3 and p38 MAPK activation is Ca(2+) and c-Src dependent,
      in agreement with the established cellular action of pX. Importantly, pX
      dependent activation of p38 MAPK inactivates Cdc25C by phosphorylation of Ser216,
      thus initiating activation of the G(2)/M checkpoint, resulting in 4pX-1 cell
      growth retardation. Interestingly, pX expression in the less differentiated
      hepatocyte 4pX-1 cells activates signaling pathways known to be active in
      regenerating hepatocytes. These results suggest that pX expression in the
      infected liver effects distinct mitogenic pathway activation in less
      differentiated versus differentiated hepatocytes.

PMID- 12208957
TI  - Increased macrophage infection upon subcutaneous inoculation of rhesus macaques
      with simian immunodeficiency virus-loaded dendritic cells or T cells but not with
      cell-free virus.
AB  - Information on the establishment of immunodeficiency virus infection through
      transmission of infected cells is sparse. Dendritic cells (DCs) and T cells may
      be central to the onset and subsequent spread of infection following mucosal
      exposure. To directly investigate the consequences of virus being introduced by
      DCs or T cells, we reinjected ex vivo simian immunodeficiency virus (SIV)-loaded
      autologous immature DCs and T cells subcutaneously (s.c.) into healthy macaques.
      s.c. injection of cell-bound virus was used to mirror what may happen if virus
      loaded cells pass through an epithelium or perhaps DCs and T cells that
      immediately entrap cell-free virus, having just crossed an epithelial barrier.
      Virus load in the plasma was monitored along with combined in situ hybridization
      and immunohistochemistry to identify the cells replicating virus in the lymphoid
      tissues. Both DCs and T cells transmitted infection after being pulsed with
      either wild-type or nef-defective (delta nef) SIVmac239. As seen in animals
      infected intravenously, replication of delta nef was attenuated compared to that
      of wild-type virus when introduced in either cell-bound form. Upon examination of
      the draining lymph nodes (LNs) during the first days of infection, virus
      producing CD4(+) T cells predominated in control animals that received s.c. cell
      free virus. In dramatic contrast, both SIV-positive macrophages and T cells were
      detected in the LNs of monkeys infected with cell-associated SIV. Therefore,
      although both cell-free and cell-associated viruses are infectious, the initial
      cells amplifying the virus differ. This may have important implications for the
      subsequent dissemination of infection and/or induction of antiretroviral
      immunity.

PMID- 12208958
TI  - Protective immunity to rabbit oral and cutaneous papillomaviruses by immunization
      with short peptides of L2, the minor capsid protein.
AB  - The papillomavirus minor capsid protein, L2, has been shown to exhibit
      immunogenicity, whereby a variety of B-cell epitopes, predominantly in the amino
      terminus of L2, have been deduced. However, immunity to L2 in vivo has not been
      examined extensively. Notably, a common neutralization epitope for human
      papillomavirus (HPV) types 6 and 16 was mapped to amino acids (aa) 108 to 120.
      The objectives of this study were to derive antisera from rabbits using the
      corresponding sequences from rabbit viruses and to assess the ability of these
      peptides to protect against infection. Synthetic peptides consisting of two
      overlapping sequences each in the region of aa 94 to 122 of the rabbit oral
      (ROPV) and cottontail rabbit (CRPV) papillomaviruses were used to immunize
      rabbits. Rabbits were then infected with both ROPV and CRPV and monitored for the
      development of oral and cutaneous papillomas, respectively. Serum derived from
      rabbits immunized with either of the two peptides was shown to (i) react to
      purified L2 from the cognate virus, (ii) specifically recognize L2 within virus
      infected cells, and (iii) neutralize virus in vitro. Following viral challenge,
      cutaneous papilloma growth was completely absent in rabbits immunized with either
      CRPV peptide. Likewise, ROPV peptide-immunized rabbits were protected from oral
      papillomatosis. Challenge of CRPV peptide-immune rabbits with the viral genome
      resulted in efficient papilloma growth, suggesting a neutralizing antibody
      mediated mechanism of protection. These results afford in vivo evidence for the
      immunogenicity provided by a distinct region of L2 and further support previous
      evidence for the ability of this region to elicit antiviral immunity.

PMID- 12208959
TI  - Identification of a G(2) arrest domain in the E1 wedge E4 protein of human
      papillomavirus type 16.
AB  - Human papillomavirus type 16 (HPV16) is the most common cause of cervical
      carcinoma. Cervical cancer develops from low-grade lesions that support the
      productive stages of the virus life cycle. The 16E1 wedge E4 protein is
      abundantly expressed in such lesions and can be detected in cells supporting
      vegetative viral genome amplification. Using an inducible mammalian expression
      system, we have shown that 16E1 wedge E4 arrests HeLa cervical epithelial cells
      in G(2). 16E1 wedge E4 also caused a G(2) arrest in SiHa, Saos-2 and
      Saccharomyces pombe cells and, as with HeLa cells, was found in the cytoplasm.
      However, whereas 16E1 wedge E4 is found on the keratin networks in HeLa and SiHa
      cells, in Saos-2 and S. pombe cells that lack keratins, 16E1 wedge E4 had a
      punctate distribution. Mutagenesis studies revealed a proline-rich region between
      amino acids 17 and 45 of 16E1 wedge E4 to be important for arrest. This region,
      which we have termed the "arrest domain," contains a putative nuclear
      localization signal, a cyclin-binding motif, and a single cyclin-dependent kinase
      (Cdk) phosphorylation site. A single point mutation in the putative Cdk
      phosphorylation site (T23A) abolished 16E1 wedge E4-mediated G(2) arrest. Arrest
      did not involve proteins regulating the phosphorylation state of Cdc2 and does
      not appear to involve the activation of the DNA damage or incomplete replication
      checkpoint. G(2) arrest was also mediated by the E1 wedge E4 protein of HPV11, a
      low-risk mucosal HPV type that also causes cervical lesions. The E1 wedge E4
      protein of HPV1, which is more distantly related to that of HPV16, did not cause
      G(2) arrest. We conclude that, like other papillomavirus proteins, 16E1 wedge E4
      affects cell cycle progression and that it targets a conserved component of the
      cell cycle machinery.

PMID- 12208960
TI  - Kinetics of expression of rhesus monkey rhadinovirus (RRV) and identification and
      characterization of a polycistronic transcript encoding the RRV Orf50/Rta, RRV
      R8, and R8.1 genes.
AB  - Rhesus monkey rhadinovirus (RRV) is a close relative of Kaposi's sarcoma
      associated herpesvirus (KSHV; human herpesvirus 8). RRV serves as an in vitro and
      an in vivo model for KSHV, and the mapping of its transcription program during
      lytic replication is significant since it represents de novo infection in the
      absence of stimulation with phorbol esters. Further, the RRV lytic system
      facilitates the making of recombinant viruses, and hence transcription profiling
      of the wild-type virus is important. Currently, the kinetics of lytic gene
      expression of RRV, the function of the RRV Orf50/Rta gene, and the presence of
      the RRV R8 and R8.1 genes are not known. This study details the transcription
      profile seen during RRV lytic replication and shows that RRV latency-associated
      nuclear antigen, viral FLIP (vFLIP), and vCyclin are transcribed during the RRV
      lytic phase. In addition, this study describes the identification of three new
      spliced products of the RRV Orf50, R8, and R8.1 genes, which are structural
      homologs of the KSHV Orf50, K8, and K8.1 genes, respectively. Characterization of
      the RRV Orf50 protein identifies it as a strong transcriptional transactivator
      capable of activating three early RRV promoters. Interestingly, the KSHV Orf50
      transactivator can also activate these simian virus promoters, suggesting that
      there exists a conservation of gene function between the key transcription
      factors of KSHV and RRV.

PMID- 12208961
TI  - A single mutation in the carboxy terminus of reovirus outer-capsid protein sigma
      3 confers enhanced kinetics of sigma 3 proteolysis, resistance to inhibitors of
      viral disassembly, and alterations in sigma 3 structure.
AB  - Mammalian reoviruses undergo acid-dependent proteolytic disassembly within
      endosomes, resulting in formation of infectious subvirion particles (ISVPs).
      ISVPs are obligate intermediates in reovirus disassembly that mediate viral
      penetration into the cytoplasm. The initial biochemical event in the reovirus
      disassembly pathway is the proteolysis of viral outer-capsid protein sigma 3.
      Mutant reoviruses selected during persistent infection of murine L929 cells (PI
      viruses) demonstrate enhanced kinetics of viral disassembly and resistance to
      inhibitors of endocytic acidification and proteolysis. To identify sequences in
      sigma 3 that modulate acid-dependent and protease-dependent steps in reovirus
      disassembly, the sigma 3 proteins of wild-type strain type 3 Dearing; PI viruses
      L/C, PI 2A1, and PI 3-1; and four novel mutant sigma 3 proteins were expressed in
      insect cells and used to recoat ISVPs. Treatment of recoated ISVPs (rISVPs) with
      either of the endocytic proteases cathepsin L or cathepsin D demonstrated that an
      isolated tyrosine-to-histidine mutation at amino acid 354 (Y354H) enhanced sigma
      3 proteolysis during viral disassembly. Yields of rISVPs containing Y354H in
      sigma3 were substantially greater than those of rISVPs lacking this mutation
      after growth in cells treated with either acidification inhibitor ammonium
      chloride or cysteine protease inhibitor E64. Image reconstructions of electron
      micrographs of virus particles containing wild-type or mutant sigma 3 proteins
      revealed structural alterations in sigma 3 that correlate with the Y354H
      mutation. These results indicate that a single mutation in sigma 3 protein alters
      its susceptibility to proteolysis and provide a structural framework to
      understand mechanisms of sigma 3 cleavage during reovirus disassembly.

PMID- 12208962
TI  - Identification and characterization of three immunodominant structural proteins
      of fowlpox virus.
AB  - Genes encoding fowlpox virus (FWPV) structural proteins have been identified
      mainly by sequence homology with those from vaccinia virus (VACV), but little is
      known about the encoded proteins. Production of monoclonal antibodies (MAbs)
      against Poxine and HP1-440 (Munich) clone FP9 allowed the identification of three
      immunodominant FWPV proteins: the 39-kDa core protein (encoded by FPV168,
      homologous to VACV A4L), a 30- and 35-kDa protein doublet, and an abundant 63-kDa
      protein. The 30- and 35-kDa proteins are nonglycosylated, antigenically related
      proteins present in the intracellular mature virus membrane and localizing
      closely with the viral factories. N-terminal sequencing identified the 35-kDa
      protein as encoded by FPV140 (the FWPV homolog of VACV H3L). The 63-kDa protein
      forms covalently linked dimers and oligomers. It remained mainly insoluble upon
      detergent treatment of purified virus but did not localize closely with the viral
      factory. N-terminal sequencing was unsuccessful, suggesting N-terminal blocking.
      CNBr digestion generated a peptide encoded by FPV191, predicted to encode one of
      two FWPV A-type inclusion (ATI) proteins. The characteristics of the 63-kDa
      protein were inconsistent with published observations on cowpox or VACV ATI
      proteins (it appears to be essential). The 63-kDa protein, however, shares
      characteristics with both VACV p4c virus occlusion and 14-kDa fusion proteins.
      Gene assignment at the poxvirus ATI locus (between VACV A24R and A28L) is
      complicated by sequence redundancies and variations, often due to deletions and
      multiple frameshift mutations. The identity of FPV191 in relation to genes at
      this locus is discussed.

PMID- 12208963
TI  - Flock house virus RNA polymerase is a transmembrane protein with amino-terminal
      sequences sufficient for mitochondrial localization and membrane insertion.
AB  - Localization of RNA replication to intracellular membranes is a universal feature
      of positive-strand RNA viruses. Replication complexes of flock house virus (FHV),
      the best-studied alphanodavirus, are located on outer mitochondrial membranes in
      infected Drosophila melanogaster cells and are associated with the formation of
      membrane-bound spherules, similar to structures found for many other positive
      strand RNA viruses. To further study FHV replication complex formation, we
      investigated the subcellular localization, membrane association, and membrane
      topology of protein A, the FHV RNA-dependent RNA polymerase, in the yeast
      Saccharomyces cerevisiae, a host able to support full FHV RNA replication and
      virion formation. Confocal immunofluorescence revealed that protein A localized
      to mitochondria in yeast, as in Drosophila cells, and that this mitochondrial
      localization was independent of viral RNA synthesis. Nycodenz gradient flotation
      and dissociation assays showed that protein A behaved as an integral membrane
      protein, a finding consistent with a predicted N-proximal transmembrane domain.
      Protease digestion and selective permeabilization after differential epitope
      tagging demonstrated that protein A was inserted into the outer mitochondrial
      membrane with the N terminus in the inner membrane space or matrix and that the C
      terminus was exposed to the cytoplasm. Flotation and immunofluorescence studies
      with deletion mutants indicated that the N-proximal region of protein A was
      important for both membrane association and mitochondrial localization. Gain-of
      function studies with green fluorescent protein fusions demonstrated that the N
      terminal 46 amino acids of protein A were sufficient for mitochondrial
      localization and membrane insertion. We conclude that protein A targets and
      anchors FHV RNA replication complexes to outer mitochondrial membranes, in part
      through an N-proximal mitochondrial localization signal and transmembrane domain.

PMID- 12208964
TI  - Memory CD4(+) T cells are the earliest detectable human immunodeficiency virus
      type 1 (HIV-1)-infected cells in the female genital mucosal tissue during HIV-1
      transmission in an organ culture system.
AB  - The virologic and cellular factors that are involved in transmission of human
      immunodeficiency virus type 1 (HIV-1) across the female genital tissue are poorly
      understood. We have recently developed a human cervical tissue-derived organ
      culture model to study heterosexual transmission of HIV-1 that mimics the in vivo
      situation. Using this model we investigated the role of phenotypic
      characteristics of HIV-1 and identified the cell types that are first infected
      during transmission. Our data indicate that the cell-free R5 HIV-1 was more
      efficiently transmitted than cell-free X4 HIV-1. Cell-free and cell-associated
      HIV-1 had comparable transmission efficiency regardless of whether the virus was
      of R5 or X4 type. We have demonstrated that memory CD4(+) T cells and not
      Langerhans cells were the first HIV-1 RNA-positive cells detected at the
      epithelial-submucosal junction 6 h after virus exposure. Multicolor laser
      confocal microscopy demonstrated a globular distribution of HIV-1 gag-pol mRNA in
      the cytoplasm, and the distribution of CD4 and the CD45RO isoform was irregular
      on the cellular membrane. At 96 h postinoculation, in addition to memory CD4(+) T
      cells, HIV-1 RNA-positive Langerhans cells and macrophages were also detected.
      The identification of CD4(+) T cells in the tissue at 6 h was confirmed by flow
      cytometric simultaneous immunophenotyping and ultrasensitive fluorescence in situ
      hybridization assay on immune cells isolated from disaggregated tissue.
      Furthermore, PMPA [9-[2-(phosphonomethoxy)propyl] adenine], an antiretroviral
      compound, and UC781, a microbicide, inhibited HIV-1 transmission across the
      mucosa, indicating the utility of the organ culture to screen topical
      microbicides for their ability to block sexual transmission of HIV-1.

PMID- 12208965
TI  - Activation of terminally differentiated human monocytes/macrophages by dengue
      virus: productive infection, hierarchical production of innate cytokines and
      chemokines, and the synergistic effect of lipopolysaccharide.
AB  - Dengue virus (DV) primarily infects blood monocytes (MO) and tissue macrophages
      (M phi). We have shown in the present study that DV can productively infect
      primary human MO/M phi regardless of the stage of cell differentiation. After DV
      infection, the in vitro-differentiated MO/M phi secreted multiple innate
      cytokines and chemokines, including tumor necrosis factor alpha, alpha interferon
      (IFN-alpha), interleukin-1 beta (IL-1 beta), IL-8, IL-12, MIP-1 alpha, and RANTES
      but not IL-6, IL-15, or nitric oxide. Secretion of these mediators was
      highlighted by distinct magnitude, onset, kinetics, duration, and induction
      potential. A chemokine-to-cytokine hierarchy was noted in the magnitude and
      induction potential of secretion, and a chemokine-to-cytokine-to-chemokine/Th1
      cytokine cascade could be seen in the production kinetics. Furthermore, we found
      that terminally differentiated MO/M phi cultured for more than 45 days could
      support productive DV infection and produce innate cytokines and chemokines,
      indicating that these mature cells were functionally competent in the context of
      a viral infection. In addition, DV replication in primary differentiated human
      MO/M phi was enhanced and prolonged in the presence of lipopolysaccharide (LPS),
      and LPS-mediated synergistic production of IFN-alpha could be seen in DV-infected
      MO/M phi. The secretion of innate cytokines and chemokines by differentiated MO/M
      phi suggests that regional accumulation of these mediators may occur in various
      tissues to which DV has disseminated and may thus result in local inflammation.
      The LPS-mediated enhancement of virus replication and synergistic IFN-alpha
      production suggests that concurrent bacterial infection may modulate cytokine
      mediated disease progression during DV infection.

PMID- 12208967
TI  - Biological significance of a human enterovirus B-specific RNA element in the 3'
      nontranslated region.
AB  - The secondary structures predicted for the enteroviral 3' nontranslated region
      (3'NTR) all seem to indicate a conformation consisting of two (X and Y) hairpin
      structures. The higher-order RNA structure of the 3'NTR appears to exist as an
      intramolecular kissing interaction between the loops of these two hairpin
      structures. The enterovirus B-like subgroup possesses an additional stem-loop
      structure, domain Z, which is not present in the poliovirus-like enteroviruses.
      It has been suggested that the Z domain originated from a burst of short sequence
      repetitions (E. V. Pilipenko, S. V. Maslova, A. N. Sinyakov, and V. I. Agol,
      Nucleic Acids Res. 20:1739-1745, 1992). However, no functional features have yet
      been ascribed to this enterovirus B-like-specific RNA element in the 3'NTR. In
      this study, we tested the functional characteristics and biological significance
      of domain Z. A mutant of the cardiovirulent coxsackievirus group B3 strain Nancy
      which completely lacked the Z domain and which therefore acquired enterovirus C
      like secondary structures exhibited a wild-type growth phenotype, as determined
      by single-cycle growth analysis with BGM cells. This result proves that the Z
      domain is virtually dispensable for viral growth in tissue cultures. Partial
      distortion of the Z domain structure resulted in a disabled virus with reduced
      growth kinetics, probably due to alternative conformations of the overall
      structure of the domain. Infection of mice showed that the recombinant
      coxsackievirus group B3 mutant which completely lacked the Z domain was less
      virulent. Pancreatic tissues from mice infected with wild-type virus and
      recombinant virus were equally affected. However, the heart tissue from mice
      infected with the recombinant virus showed only slight signs of myocarditis.
      These results suggest that the enterovirus B-like-specific Z domain plays a role
      in coxsackievirus-induced pathogenesis.

PMID- 12208966
TI  - Mutagenic stabilization and/or disruption of a CD4-bound state reveals distinct
      conformations of the human immunodeficiency virus type 1 gp120 envelope
      glycoprotein.
AB  - The human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope
      glycoprotein is conformationally flexible. Upon binding to the host cell receptor
      CD4, gp120 assumes a conformation that is recognized by the second receptor, CCR5
      and/or CXCR4, and by the CD4-induced (CD4i) antibodies. Guided by the X-ray
      crystal structure of a gp120-CD4-CD4i antibody complex, we introduced changes
      into gp120 that were designed to stabilize or disrupt this conformation. One
      mutant, 375 S/W, in which the tryptophan indole group is predicted to occupy the
      Phe 43 cavity in the gp120 interior, apparently favors a gp120 conformation
      closer to that of the CD4-bound state. The 375 S/W mutant was recognized as well
      as or better than wild-type gp120 by CD4 and CD4i antibodies, and the large
      decrease in entropy observed when wild-type gp120 bound CD4 was reduced for the
      375 S/W mutant. The recognition of the 375 S/W mutant by CD4BS antibodies, which
      are directed against the CD4-binding region of gp120, was markedly reduced
      compared with that of the wild-type gp120. Compared with the wild-type virus,
      viruses with the 375 S/W envelope glycoproteins were resistant to neutralization
      by IgG1b12, a CD4BS antibody, were slightly more sensitive to soluble CD4
      neutralization and were neutralized more efficiently by the 2G12 antibody.
      Another mutant, 423 I/P, in which the gp120 bridging sheet was disrupted, did not
      bind CD4, CCR5, or CD4i antibodies, even though recognition by CD4BS antibodies
      was efficient. These results indicate that CD4BS antibodies recognize
      conformations of gp120 different from that recognized by CD4 and CD4i antibodies.

PMID- 12208968
TI  - Large hepatitis delta antigen is not a suppressor of hepatitis delta virus RNA
      synthesis once RNA replication is established.
AB  - Moderation of hepatitis delta virus (HDV) replication is a likely prerequisite in
      the establishment of chronic infections and is thought to be mediated by the
      intracellular accumulation of large hepatitis delta antigen (L-HDAg). The
      regulatory role of this protein was suggested from several studies showing that
      cotransfection of plasmid cDNAs expressing both L-HDAg and HDV RNA results in a
      potent inhibition of HDV RNA replication. However, since this approach differs
      significantly from natural HDV infections, where HDV RNA replication is initiated
      from an RNA template, and L-HDAg appears only late in the replication cycle, it
      remains unclear whether L-HDAg can modulate HDV RNA replication in the natural
      HDV replication cycle. In this study, we investigated the effect of L-HDAg,
      produced as a result of the natural HDV RNA editing event, on HDV RNA
      replication. The results showed that following cDNA-free HDV RNA transfection, a
      steady-state level of RNA was established at 3 to 4 days posttransfection. The
      same level of HDV RNA was reached when a mutant HDV genome unable to make L-HDAg
      was used, suggesting that L-HDAg did not play a role. The rates of HDV RNA
      synthesis, as measured by metabolic labeling experiments, were identical at 4 and
      8 days posttransfection and in the wild type and the L-HDAg-deficient mutant. We
      further examined the effect of overexpression of L-HDAg at various stages of the
      HDV replication cycle, showing that HDV RNA synthesis was resistant to L-HDAg
      when it was overexpressed 3 days after HDV RNA replication had initiated.
      Finally, we showed that, contrary to conventional thinking, L-HDAg alone, at a
      certain molar ratio with HDV RNA, can initiate HDV RNA replication. Thus, L-HDAg
      does not inherently inhibit HDV RNA synthesis. Taken together, these results
      indicated that L-HDAg affects neither the rate of HDV RNA synthesis nor the final
      steady-state level of HDV RNA and that L-HDAg is unlikely to act as an inhibitor
      of HDV RNA replication in the natural HDV replication cycle.

PMID- 12208969
TI  - Strategy for nonenveloped virus entry: a hydrophobic conformer of the reovirus
      membrane penetration protein micro 1 mediates membrane disruption.
AB  - The mechanisms employed by nonenveloped animal viruses to penetrate the membranes
      of their host cells remain enigmatic. Membrane penetration by the nonenveloped
      mammalian reoviruses is believed to deliver a partially uncoated, but still large
      ( approximately 70-nm), particle with active transcriptases for viral mRNA
      synthesis directly into the cytoplasm. This process is likely initiated by a
      particle form that resembles infectious subvirion particles (ISVPs), disassembly
      intermediates produced from virions by proteolytic uncoating. Consistent with
      that idea, ISVPs, but not virions, can induce disruption of membranes in vitro.
      Both activities ascribed to ISVP-like particles, membrane disruption in vitro and
      membrane penetration within cells, are linked to N-myristoylated outer-capsid
      protein micro 1, present in 600 copies at the surfaces of ISVPs. To understand
      how micro 1 fulfills its role as the reovirus penetration protein, we monitored
      changes in ISVPs during the permeabilization of red blood cells induced by these
      particles. Hemolysis was preceded by a major structural transition in ISVPs,
      characterized by conformational change in micro 1 and elution of fibrous
      attachment protein sigma 1. The altered conformer of micro 1 was required for
      hemolysis and was markedly hydrophobic. The structural transition in ISVPs was
      further accompanied by derepression of genome-dependent mRNA synthesis by the
      particle-associated transcriptases. We propose a model for reovirus entry in
      which (i) primed and triggered conformational changes, analogous to those in
      enveloped-virus fusion proteins, generate a hydrophobic micro 1 conformer capable
      of inserting into and disrupting cell membranes and (ii) activation of the viral
      particles for membrane interaction and mRNA synthesis are concurrent events.
      Reoviruses provide an opportune system for defining the molecular details of
      membrane penetration by a large nonenveloped animal virus.

PMID- 12208970
TI  - In rat dorsal root ganglion neurons, herpes simplex virus type 1 tegument forms
      in the cytoplasm of the cell body.
AB  - The herpes simplex virus type 1 (HSV-1) tegument is the least understood
      component of the virion, and the mechanism of tegument assembly and incorporation
      into virions during viral egress has not yet been elucidated. In the present
      study, the addition of tegument proteins (VP13/14, VP16, VP22, and US9) and
      envelope glycoproteins (gD and gH) to herpes simplex virions in the cell body of
      rat dorsal root ganglion neurons was examined by immunoelectron microscopy. All
      tegument proteins were detected diffusely spread in the nucleus within 10 to 12 h
      and, at these times, nucleocapsids were observed budding from the nucleus. The
      majority (96%) of these nucleocapsids had no detectable label for tegument and
      glycoproteins despite the presence of tegument proteins in the nucleus and
      glycoproteins adjacent to the nuclear membrane. Immunolabeling for tegument
      proteins and glycoproteins was found abundantly in the cytoplasm of the cell body
      in multiple discrete vesicular areas: on unenveloped, enveloped, or partially
      enveloped capsids adjacent to these vesicles and in extracellular virions. These
      vesicles and intracytoplasmic and extracellular virions also labeled with Golgi
      markers, giantin, mannosidase II, and TGN38. Treatment with brefeldin A from 2 to
      24 h postinfection markedly inhibited incorporation into virions of VP22 and US9
      but to a lesser degree with VP16 and VP13/14. These results suggest that, in the
      cell body of neurons, most tegument proteins are incorporated into unenveloped
      nucleocapsids prior to envelopment in the Golgi and the trans-Golgi network.
      These findings give further support to the deenvelopment-reenvelopment hypothesis
      for viral egress. Finally, the addition of tegument proteins to unenveloped
      nucleocapsids in the cell body allows access to these unenveloped nucleocapsids
      to one of two pathways: egress through the cell body or transport into the axon.

PMID- 12208971
TI  - Inhibitory activity of synthetic peptide antibiotics on feline immunodeficiency
      virus infectivity in vitro.
AB  - Natural peptide antibiotics are part of host innate immunity against a wide range
      of microbes, including some viruses. Synthetic peptides modeled after natural
      peptide antibiotics interfere with microbial membranes and are termed peptidyl
      membrane-interactive molecules (peptidyl-MIM [Demegen Inc, Pittsburgh, Pa.]).
      Sixteen peptidyl-MIM candidates were tested for activity against feline
      immunodeficiency virus (FIV) on infected CrFK cells. Three of them (D4E1, DC1,
      and D1D6) showed potent anti-FIV activity in chronically infected CrFK cells as
      measured by decreased reverse transcriptase (RT) activity, having 50% inhibitory
      concentrations of 0.46, 0.75, and 0.94 micro M, respectively, which were
      approximately 10 times lower than their direct cytotoxic concentrations.
      Treatment of chronically infected CrFK cells with 2 micro M D4E1 for 3 days
      completely reversed virus-induced cytopathic effect. Immunofluorescence revealed
      reduced p26 staining in these cells. Treatment of chronically infected CrFK cells
      with 2 micro M D4E1 suppressed virus production ( approximately 50%) for up to 7
      days, The virions from the D4E1-treated culture had impaired infectivity, as
      measured by the 50% tissue culture infectious dose and nested PCR analysis of
      proviral DNA. However, these noninfectious virions were able to bind and
      internalize, suggesting a defect at some postentry step. After chronically
      infected CrFK cells were treated with D4E1 for 24 h, increased cell-associated
      mature p26 Gag and decreased extracellular virus-associated p26 Gag were observed
      by Western blot analysis, suggesting that virus assembly and/or release may be
      blocked by D4E1 treatment, whereas virus binding, penetration, RNA synthesis, and
      protein synthesis appear to be unaffected. Synthetic peptide antibiotics may be
      useful tools in the search for antiviral drugs having a wide therapeutic window
      for host cells.

PMID- 12208972
TI  - Intact microtubules support adenovirus and herpes simplex virus infections.
AB  - Capsids and the enclosed DNA of adenoviruses, including the species C viruses
      adenovirus type 2 (Ad2) and Ad5, and herpesviruses, such as herpes simplex virus
      type 1 (HSV-1), are targeted to the nuclei of epithelial, endothelial,
      fibroblastic, and neuronal cells. Cytoplasmic transport of fluorophore-tagged Ad2
      and immunologically detected HSV-1 capsids required intact microtubules and the
      microtubule-dependent minus-end-directed motor complex dynein-dynactin. A recent
      study with epithelial cells suggested that Ad5 was transported to the nucleus and
      expressed its genes independently of a microtubule network. To clarify the
      mechanisms by which Ad2 and, as an independent control, HSV-1 were targeted to
      the nucleus, we treated epithelial cells with nocodazole (NOC) to depolymerize
      microtubules and measured viral gene expression at different times and
      multiplicities of infections. Our results indicate that in NOC-treated cells,
      viral transgene expression was significantly reduced at up to 48 h postinfection
      (p.i.). A quantitative analysis of subcellular capsid localization indicated that
      NOC blocked the nuclear targeting of Ad2 and also HSV-1 by more than 90% at up to
      7 h p.i. About 10% of the incoming Texas Red-coupled Ad2 (Ad2-TR) was enriched at
      the nucleus in microtubule-depleted cells at 5 h p.i. This result is consistent
      with earlier observations that Ad2-TR capsids move randomly in NOC-treated cells
      at less than 0.1 micro m/s and over distances of less than 5 micro m,
      characteristic of Brownian motion. We conclude that fluorophore-tagged Ad2 and
      HSV-1 particles are infectious and that microtubules play a prominent role in
      efficient nuclear targeting during entry and gene expression of species C Ads and
      HSV-1.

PMID- 12208973
TI  - Large-scale, pH-dependent, quaternary structure changes in an RNA virus capsid
      are reversible in the absence of subunit autoproteolysis.
AB  - The assembly and maturation of the coat protein of a T=4, nonenveloped, single
      stranded RNA virus, Nudaurelia capensis omega virus (N omega V), was examined by
      using a recombinant baculovirus expression system. At pH 7.6, the coat protein
      assembles into a stable particle called the procapsid, which is 450 A in diameter
      and porous. Lowering the pH to 5.0 leads to a concerted reorganization of the
      subunits into a 410-A-diameter particle called the capsid, which has no obvious
      pores. This conformational change is rapid but reversible until slow,
      autoproteolytic cleavage occurs in at least 15% of the subunits at the lower pH.
      In this report, we show that expression of subunits with replacement of Asn-570,
      which is at the cleavage site, with Thr results in assembly of particles with
      expected morphology but that are cleavage defective. The conformational change
      from procapsid to capsid is reversible in N570T mutant virus-like particles, in
      contrast to wild-type particles, which are locked into the capsid conformation
      after cleavage of the coat protein. The reexpanded procapsids display slightly
      different properties than the original procapsid, suggesting hysteretic effects.
      Because of the stability of the procapsid under near-neutral conditions and the
      reversible properties of the cleavage-defective mutant, N omega V provides an
      excellent model for the study of pH-induced conformational changes in
      macromolecular assemblies. Here, we identify the relationship between cleavage
      and the conformational change and propose a pH-dependent helix-coil transition
      that may be responsible for the structural rearrangement in N omega V.

PMID- 12208974
TI  - Decreased levels of recent thymic emigrants in peripheral blood of simian
      immunodeficiency virus-infected macaques correlate with alterations within the
      thymus.
AB  - The thymus is responsible for de novo production of CD4(+) and CD8(+) T cells and
      therefore is essential for T-cell renewal. The goal of this study was to assess
      the impact of simian immunodeficiency virus (SIV) infection on the production of
      T cells by the thymus. Levels of recent thymic emigrants within the peripheral
      blood were assessed through quantification of macaque T-cell receptor excision
      circles (TREC). Comparison of SIV-infected macaques (n = 15) to uninfected
      macaques (n = 23) revealed stable or increased TREC levels at 20 to 34 weeks
      postinfection. Further assessment of SIV-infected macaques (n = 4) determined
      that TREC levels decreased between 24 and 48 weeks postinfection. Through the
      assessment of longitudinal time points in three additional SIVmac239-infected
      macaques, the SIV infection was divided into two distinct phases. During phase 1
      (16 to 30 weeks), TREC levels remained stable or increased within both the CD4
      and CD8 T-cell populations. During phase 2 (after 16 to 30 weeks), TREC levels
      declined in both T-cell populations. As has been described for human
      immunodeficiency virus (HIV)-infected patients, this decline in TREC levels did
      at times correlate with an increased level of T-cell proliferation (Ki67(+)
      cells). However, not all TREC decreases could be attributed to increased T-cell
      proliferation. Further evidence for thymic dysfunction was observed directly in a
      SIVmac239-infected macaque that succumbed to simian AIDS at 65 weeks
      postinfection. The thymus of this macaque contained an increased number of
      memory/effector CD8(+) T cells and an increased level of apoptotic cells. In
      summary, reduced levels of TREC can be observed beginning at 16 to 30 weeks post
      SIV infection and correlate with changes indicative of dysfunction within the
      thymic tissue. SIV infection of macaques will be a useful model system to
      elucidate the mechanisms responsible for the thymic dysfunction observed in HIV
      infected patients.

PMID- 12208975
TI  - The African swine fever virus protein j4R binds to the alpha chain of nascent
      polypeptide-associated complex.
AB  - The African swine fever virus (ASFV) j4R protein is expressed late during the
      virus replication cycle and is present in both the nucleus and the cytoplasm of
      infected cells. By using the yeast two-hybrid system, direct binding, and
      coprecipitation from cells, we showed that the j4R protein binds to the alpha
      chain of nascent polypeptide-associated complex (alpha NAC). Confocal microscopy
      indicated that a proportion of j4R and alpha NAC interact in areas close to the
      plasma membrane, as well as through the cytoplasm in cells. In vitro binding
      studies suggested that binding of j4R to alpha NAC did not interfere with the
      binding of alpha- and beta NAC subunits (the BTF3 transcription factor).

PMID- 12208976
TI  - Three isoforms of cyclophilin A associated with human immunodeficiency virus type
      1 were found by proteomics by using two-dimensional gel electrophoresis and
      matrix-assisted laser desorption ionization-time of flight mass spectrometry.
AB  - Human immunodeficiency virus type 1 (HIV-1) strain LAV-1 (HIV-1(LAV-1)) particles
      were collected by ultracentrifugation, treated with subtilisin, and then purified
      by Sepharose CL-4B column chromatography to remove microvesicles. The lysate of
      the purified HIV-1(LAV-1) particles was subjected to two-dimensional (2D) gel
      electrophoresis and stained. The 2D gel electrophoresis image suggested that 24
      proteins can be identified inside the virion. Furthermore, the stained protein
      spots were excised and digested with trypsin. The resulting peptide fragments
      were characterized by matrix-assisted laser desorption ionization-time of flight
      mass spectrometry. Peptide mass fingerprinting data suggested that two isoforms
      of cyclophilin A (CyPA), one with an isoelectric point (pI) of 6.40 and one with
      a pI of 6.53, are inside the viral membrane; that another isoform, with a pI of
      6.88, is outside the viral membrane; and that the CyPA isoform with a pI of 6.53
      is N acetylated. The mechanisms that permit the redistribution of CyPA on the
      viral surface have not yet been clarified, but it is surmised that the CyPA
      isoform with a pI of 6.88 may play a critical role in the attachment of virions
      to the surface of target cells and that both CyPA isoforms with pIs of 6.40 and
      6.53 may regulate the conformation of the HIV-1 capsid protein.

PMID- 12208977
TI  - Assembly and translocation of papillomavirus capsid proteins.
AB  - The major and minor capsid proteins of polyomavirus are preassembled in the
      cytoplasm and translocated to the nucleus only as a VP1-VP2/VP3 complex. In this
      study, we describe independent nuclear translocation of the L1 major protein and
      the L2 minor capsid protein of human papillomavirus type 33 by several
      approaches. First, we observed that expression and nuclear translocation of L2 in
      natural lesions precede expression of L1. Second, using a cell culture system for
      coexpression, we found that accumulation of L2 in nuclear domain 10 (ND10)
      subnuclear structures precedes L1 by several hours. In contrast, complexes of L2
      and mutants of L1 forced to assemble in the cytoplasm are translocated directly
      to ND10, like L2 expressed alone. Interestingly, accumulation of wild-type L1 is
      observed only after L2-induced release of the ND10-associated protein Sp100.
      Third, nuclear translocation of L2 but not of L1 was blocked by the proteasome
      inhibitor MG132. Our data suggest that L1 and L2 interaction occurs after L2
      induced reorganization of ND10 subnuclear domains.

PMID- 12208978
TI  - Crystal structures of Zidovudine- or Lamivudine-resistant human immunodeficiency
      virus type 1 reverse transcriptases containing mutations at codons 41, 184, and
      215.
AB  - Six structures of human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT) containing combinations of resistance mutations for zidovudine
      (AZT) (M41L and T215Y) or lamivudine (M184V) have been determined as inhibitor
      complexes. Minimal conformational changes in the polymerase or nonnucleoside RT
      inhibitor sites compared to the mutant RTMC (D67N, K70R, T215F, and K219N) are
      observed, indicating that such changes may occur only with certain combinations
      of mutations. Model building M41L and T215Y into HIV-1 RT-DNA and docking in ATP
      that is utilized in the pyrophosphorolysis reaction for AZT resistance indicates
      that some conformational rearrangement appears necessary in RT for ATP to
      interact simultaneously with the M41L and T215Y mutations.

PMID- 12208979
TI  - Lack of canonical E6 and E7 open reading frames in bird papillomaviruses:
      Fringilla coelebs papillomavirus and Psittacus erithacus timneh papillomavirus.
AB  - Determination and analyses of the complete sequence of Fringilla coelebs
      papillomavirus and Psittacus erithacus timneh papillomavirus indicate that they
      represent a distinct and distant lineage of papillomaviruses. The lack of
      canonical E6-E7 open reading frames suggests that they serve adaptive functions
      during papillomavirus evolution.

PMID- 12208980
TI  - The PPPY motif of human T-cell leukemia virus type 1 Gag protein is required
      early in the budding process.
AB  - Domains required late in the virus budding process (L domains) have been
      identified in the Gag proteins of a number of retroviruses. Here we show that the
      human T-cell leukemia virus type 1 candidate L domain motif PPPY is indeed
      required for virus production. Strikingly, however, mutation of this motif
      arrested virus particles at an earlier stage in the budding process than was seen
      for mutation of the L domain motifs thus far described for retroviruses. In view
      of the exchangeability of such domains, we propose that the retrovirus budding
      process may involve a continuum from bud formation to membrane fission.

PMID- 12208981
TI  - The Epstein-Barr virus immediate-early protein BZLF1 induces both a G(2) and a
      mitotic block.
AB  - The Epstein-Barr virus immediate-early protein BZLF1 is a transcriptional
      activator that mediates the switch from latent to lytic infection. Here we
      demonstrate that BZLF1 induces both a G(2) block and a mitotic block in HeLa
      cells and inhibits chromosome condensation. While the G(2) block is associated
      with decreased cyclin B1 in host cells and can be rescued by overexpression of
      cyclin B1, the mechanism for the mitotic defect is as yet undetermined.

PMID- 12208982
TI  - Sustained peptide-specific gamma interferon T-cell response in rhesus macaques
      immunized with human immunodeficiency virus gag DNA vaccines.
AB  - We examined the influence of dose and method of antigen delivery on the dynamics
      and durability of T-cell responses to candidate human immunodeficiency virus
      (HIV) vaccines. Codon-optimized sequences from the HIV gag gene were inserted
      into alternative DNA vaccine vectors to express the coding sequence with or
      without the tissue plasminogen activator leader sequence. We delivered the
      vaccines by intramuscular injection as plasmid DNA without adjuvant or as plasmid
      DNA formulated with a novel block copolymer adjuvant (CRL8623) and then monitored
      the ensuing T-cell responses by using a gamma interferon enzyme-linked immunospot
      assay. We demonstrated persistence of the cell-mediated immune (CMI) response in
      rhesus macaques for at least 18 months following a four-dose vaccination regimen.
      The plasmid vaccine, with or without CRL8623, was immunogenic in macaques;
      however, the form coadministered with adjuvant exhibited improved T-cell
      responses, with a bias toward more antigen-specific CD8(+) T cells. Finally, we
      examined the fine specificity of the T-cell response to the gag vaccines by
      testing the response of 23 vaccinated macaques to individual Gag 20-mer peptides.
      Collectively, the monkeys responded to 25 epitopes, and, on average, each monkey
      recognized a minimum of 2.7 epitopes. The results indicate that a broad and
      durable CMI response to HIV DNA vaccines can be induced in a relevant nonhuman
      primate model.

PMID- 12208983
TI  - Immune responses to the major capsid protein during parvovirus infection of rats.
AB  - Rat virus (RV) is a common parvovirus of laboratory rodents which can disrupt rat
      based research. Prenatal or perinatal infection can be pathogenic or lead to
      persistent infection, whereas infection of adult rats is typically self-limiting.
      Effects on the host immune system have been documented during RV infection, but
      little is known about immune responses necessary for viral clearance. Our studies
      were conducted to identify humoral and cellular responses to the predominant
      capsid protein, VP2, during experimental infection of adult rats. We observed VP2
      specific proliferation, gamma interferon production, and an immunoglobulin G2a
      humoral response that is maintained for at least 35 days following RV infection.
      These results strongly suggest the induction of virus-specific Th1-mediated
      immunity.

PMID- 12208984
TI  - Reversal by dithiothreitol treatment of the block in murine leukemia virus
      maturation induced by disulfide cross-linking.
AB  - We previously reported that if murine leukemia virus particles are produced in
      the presence of the mild oxidizing agent disulfide-substituted benzamide-2, they
      fail to undergo the normal process of virus maturation. We now show that
      treatment of these immature particles with a reducing agent (dithiothreitol)
      induces their maturation in vitro, as evidenced by proteolytic cleavage of Gag,
      Gag-Pol, and Env proteins and by their morphology. The identification of partial
      cleavage products in these particles suggests the sequence with which the
      cleavages occur under these conditions. This may be a useful experimental system
      for further analysis of retroviral maturation under controlled conditions in
      vitro.

PMID- 12208985
TI  - First molecular evidence for the existence of distinct fish and snake
      adenoviruses.
AB  - From adenovirus-like viruses originating from a fish and a snake species, a
      conserved part of the adenoviral DNA polymerase gene was PCR amplified, cloned
      and sequenced. Phylogenetic analysis showed that the snake adenovirus is closely
      related to the members of the proposed genus Atadenovirus, whereas the fish
      isolate seems to represent a separate cluster, likely a new genus.

PMID- 12208986
TI  - A hepatitis B surface antigen mutant that lacks the antigenic loop region can
      self-assemble and interact with the large hepatitis delta antigen.
AB  - A novel hepatitis B virus surface antigen mutant harboring a deletion of most of
      the major antigenic loop region was competent for self-assembly and secretion.
      Although the mutant protein was competent for interaction with and incorporation
      of free large hepatitis delta antigen, it was partially defective in hepatitis
      delta virus RNP incorporation.

PMID- 12208987
TI  - Detection and analysis of hepatitis C virus sequences in cerebrospinal fluid.
AB  - Hepatitis C virus (HCV) sequences were detected in cerebrospinal fluid (CSF) in 8
      of 13 HCV-positive patients. In four patients harboring different virus strains
      in serum and peripheral blood mononuclear cells (PBMC), CSF-derived virus was
      similar to that found in PBMC, which suggests that PBMC could carry HCV into the
      brain.

PMID- 12208988
TI  - Pregenomic RNA is required for efficient incorporation of pol polyprotein into
      foamy virus capsids.
AB  - The foamy virus (FV) Pol polyprotein is translated independently of Gag from a
      spliced mRNA. This method of expression raises the question of how Pol is
      associated with the viral particle. Using a transient FV vector transfection
      system, it is shown that pregenomic RNA is required for efficient virion
      incorporation of functionally active Pol and that protein-protein interactions of
      Pol with Gag are not sufficient to complete particle assembly.

PMID- 12208989
TI  - Asian genotypes of JC virus in Japanese-Americans suggest familial transmission.
AB  - To examine the mode of JC virus (JCV) transmission, we collected urine samples
      from second- and third-generation Japanese-Americans in Los Angeles, Calif.,
      whose parents and grandparents were all Japanese. From the urine samples of these
      Japanese-Americans, we mainly detected two subtypes (CY and MY) of JCV that are
      predominantly found among native Japanese. This finding provides support for the
      hypothesis that JCV is transmitted mainly within the family through long-term
      cohabitation.

PMID- 12208990
TI  - Association of plasma viral RNA load with prognosis in cats naturally infected
      with feline immunodeficiency virus.
AB  - We measured the quantity of plasma feline immunodeficiency virus (FIV) RNA using
      a real-time sequence detecting system. Plasma viral RNA load was shown to
      correlate with the clinical stage, survival time, and disease progression in
      naturally FIV-infected cats. The present study indicates that the plasma viral
      RNA load can be used as a clinical marker representing the impairment of the
      immune system and predicting the clinical outcome in FIV-infected cats.

PMID- 12208991
TI  - Inhibition of herpes simplex virus replication by WAY-150138: assembly of capsids
      depleted of the portal and terminase proteins involved in DNA encapsidation.
AB  - Studies were carried out to examine the mechanism of action of WAY-150138, a
      member of a novel group of thiourea compounds recently shown to inhibit
      replication of herpes simplex virus type 1 (HSV-1). Previous studies have shown
      that the drug acts by preventing DNA encapsidation and that resistant mutants map
      to U(L)6, the gene encoding the protein subunit of the portal complex through
      which DNA enters the capsid. We tested the idea that WAY-150138 acts by
      preventing the incorporation of DNA-packaging proteins into capsids as they are
      assembled. Capsids were isolated from HSV-1-infected, drug-treated cells and
      examined by Western immunoblotting for the presence of two packaging proteins,
      the portal subunit (U(L)6) and a candidate terminase subunit (U(L)15). The
      results showed that both proteins were depleted in the capsids, suggesting that
      WAY-150138 antagonizes DNA encapsidation by depriving capsids of packaging
      proteins during the assembly process.

PMID- 12208992
TI  - Paracrine factors in tubuloglomerular feedback: adenosine, ATP, and nitric oxide.
AB  - The tubuloglomerular feedback response, the change in afferent arteriolar tone
      caused by a change in NaCl concentration at the macula densa, is likely initiated
      by the generation of a vasoactive mediator within the confines of the
      juxtaglomerular apparatus. Substantial progress has been made in identifying the
      nature of this mediator and the factors that modulate its effect on vascular
      tone. In support of earlier studies using P1 purinergic antagonists, the
      application of the knockout technique has shown that adenosine 1 receptors are
      absolutely required for eliciting TGF responses. The background level of
      angiotensin II appears to be an important cofactor determining the efficiency of
      A1AR-induced vasoconstriction, probably through a synergistic interaction at the
      level of the G protein-dependent transduction mechanism. The source of the
      adenosine is still unclear, but it is conceivable that adenosine is generated
      extracellularly from released ATP through a cascade of ecto-nucleotidases. There
      is also evidence that ATP may activate P2 receptors in preglomerular vessels,
      which may contribute to autoregulation of renal vascular resistance. Nitric oxide
      (NO), generated by the neuronal isoform of nitric oxide synthase in macula densa
      cells, reduces the constrictor effect of adenosine, but the regulation of NO
      release and its exact role in states of TGF-induced hyperfiltration are still
      unclear.

PMID- 12208993
TI  - Processive and nonprocessive models of kinesin movement.
AB  - Conventional kinesin is the prototypic member of a family of diverse proteins
      that use the chemical energy of ATP hydrolysis to generate force and move along
      microtubules. These proteins, which are involved in a wide range of cellular
      functions, have been identified in protozoa, fungi, plants, and animals and
      possess a high degree of sequence conservation among species in their motor
      domains. The biochemical properties of kinesin and its homologues, in conjunction
      with the recently solved three-dimensional structures of several kinesin motors,
      have contributed to our understanding of the mechanism of kinesin movement along
      microtubules. We discuss several models for movement, including the hand-over
      hand, inchworm, and biased diffusion models of processive movement, as well as
      models of nonprocessive movement.

PMID- 12208994
TI  - Terminal differentiation of intercalated cells: the role of hensin.
AB  - During the response to metabolic acidosis, the intercalated cell of the
      collecting tubule converts from one that secretes HCO3(-) to one that absorbs
      HCO3(-) by H(+) secretion. The molecular basis of this complex change in
      phenotype was studied in an immortalized intercalated cell line. We found that it
      was induced by secretion, polymerization, and deposition of a protein, which we
      termed hensin, into the extracellular matrix. Surprisingly, this change in
      phenotype is identical to terminal differentiation of epithelial cells in that it
      recapitulated all the characteristics of terminal differentiation, including a
      change in cell shape, acquisition of specialized apical structures (microvilli
      and ruffles), and the ability to secrete and endocytose materials in a regulated
      manner from the apical membrane. Hensin is expressed in most epithelia, and
      others have discovered that it is deleted in a large number of epithelial tumors.
      These results suggest that conversion of polarity of the intercalated cells
      represents a process of terminal differentiation.

PMID- 12208995
TI  - Signal transduction and regulatory mechanisms involved in control of the sigma(S)
      (RpoS) subunit of RNA polymerase.
AB  - The sigma(S) (RpoS) subunit of RNA polymerase is the master regulator of the
      general stress response in Escherichia coli and related bacteria. While rapidly
      growing cells contain very little sigma(S), exposure to many different stress
      conditions results in rapid and strong sigma(S) induction. Consequently,
      transcription of numerous sigma(S)-dependent genes is activated, many of which
      encode gene products with stress-protective functions. Multiple signal
      integration in the control of the cellular sigma(S) level is achieved by rpoS
      transcriptional and translational control as well as by regulated sigma(S)
      proteolysis, with various stress conditions differentially affecting these levels
      of sigma(S) control. Thus, a reduced growth rate results in increased rpoS
      transcription whereas high osmolarity, low temperature, acidic pH, and some late
      log-phase signals stimulate the translation of already present rpoS mRNA. In
      addition, carbon starvation, high osmolarity, acidic pH, and high temperature
      result in stabilization of sigma(S), which, under nonstress conditions, is
      degraded with a half-life of one to several minutes. Important cis-regulatory
      determinants as well as trans-acting regulatory factors involved at all levels of
      sigma(S) regulation have been identified. rpoS translation is controlled by
      several proteins (Hfq and HU) and small regulatory RNAs that probably affect the
      secondary structure of rpoS mRNA. For sigma(S) proteolysis, the response
      regulator RssB is essential. RssB is a specific direct sigma(S) recognition
      factor, whose affinity for sigma(S) is modulated by phosphorylation of its
      receiver domain. RssB delivers sigma(S) to the ClpXP protease, where sigma(S) is
      unfolded and completely degraded. This review summarizes our current knowledge
      about the molecular functions and interactions of these components and tries to
      establish a framework for further research on the mode of multiple signal input
      into this complex regulatory system.

PMID- 12208996
TI  - Critical role of human T-lymphotropic virus type 1 accessory proteins in viral
      replication and pathogenesis.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1) infection is associated with a
      diverse range of lymphoproliferative and neurodegenerative diseases, yet
      pathogenic mechanisms induced by the virus remain obscure. This complex
      retrovirus contains typical structural and enzymatic genes but also unique
      regulatory and accessory genes in four open reading frames (ORFs) of the pX
      region of the viral genome (pX ORFs I to IV). The regulatory proteins encoded by
      pX ORFs III and IV, Tax and Rex, respectively, have been extensively
      characterized. In contrast the contribution of the four accessory proteins
      p12(I), p27(I), p13(II), and p30(II), encoded by pX ORFs I and II, to viral
      replication and pathogenesis remained unclear. Proviral clones that are mutated
      in either pX ORF I or II, while fully competent in cell culture, are severely
      limited in their replicative capacity in a rabbit model. Emerging evidence
      indicates that the HTLV-1 accessory proteins are critical for establishment of
      viral infectivity, enhance T-lymphocyte activation, and potentially alter gene
      transcription and mitochondrial function. HTLV-1 pX ORF I expression is critical
      to the viral infectivity in resting primary lymphocytes, suggesting a role for
      p12(I) in lymphocyte activation. The endoplasmic reticulum and cis-Golgi
      localizing p12(I), encoded from pX ORF I, activates NFAT, a key T-cell
      transcription factor, through calcium-mediated signaling pathways and may lower
      the threshold of lymphocyte activation via the JAK/STAT pathway. In contrast
      p30(II) localizes to the nucleus and represses viral promoter activity, but may
      regulate cellular gene expression through p300/CBP or related coactivators of
      transcription. p13(II) targets mitochondrial proteins, where it alters the
      organelle morphology and may influence energy metabolism. Collectively, studies
      of the molecular functions of the HTLV-1 accessory proteins provide insight into
      strategies used by retroviruses that are associated with lymphoproliferative
      diseases.

PMID- 12208998
TI  - Regulation of gene expression by ambient pH in filamentous fungi and yeasts.
AB  - Life, as we know it, is water based. Exposure to hydroxonium and hydroxide ions
      is constant and ubiquitous, and the evolutionary pressure to respond
      appropriately to these ions is likely to be intense. Fungi respond to their
      environments by tailoring their output of activities destined for the cell
      surface or beyond to the ambient pH. We are beginning to glimpse how they sense
      ambient pH and transmit this information to the transcription factor, whose roles
      ensure that a suitable collection of gene products will be made. Although
      relatively little is known about pH signal transduction itself, its consequences
      for the cognate transcription factor are much clearer. Intriguingly, homologues
      of components of this system mediating the regulation of fungal gene expression
      by ambient pH are to be found in the animal kingdom. The potential applied
      importance of this regulatory system lies in its key role in fungal pathogenicity
      of animals and plants and in its control of fungal production of toxins,
      antibiotics, and secreted enzymes.

PMID- 12208997
TI  - Human telomerase and its regulation.
AB  - The telomere is a special functional complex at the end of linear eukaryotic
      chromosomes, consisting of tandem repeat DNA sequences and associated proteins.
      It is essential for maintaining the integrity and stability of linear eukaryotic
      genomes. Telomere length regulation and maintenance contribute to normal human
      cellular aging and human diseases. The synthesis of telomeres is mainly achieved
      by the cellular reverse transcriptase telomerase, an RNA-dependent DNA polymerase
      that adds telomeric DNA to telomeres. Expression of telomerase is usually
      required for cell immortalization and long-term tumor growth. In humans,
      telomerase activity is tightly regulated during development and oncogenesis. The
      modulation of telomerase activity may therefore have important implications in
      antiaging and anticancer therapy. This review describes the currently known
      components of the telomerase complex and attempts to provide an update on the
      molecular mechanisms of human telomerase regulation.

PMID- 12208999
TI  - Relationship between secondary metabolism and fungal development.
AB  - Filamentous fungi are unique organisms-rivaled only by actinomycetes and plants
      in producing a wide range of natural products called secondary metabolites. These
      compounds are very diverse in structure and perform functions that are not always
      known. However, most secondary metabolites are produced after the fungus has
      completed its initial growth phase and is beginning a stage of development
      represented by the formation of spores. In this review, we describe secondary
      metabolites produced by fungi that act as sporogenic factors to influence fungal
      development, are required for spore viability, or are produced at a time in the
      life cycle that coincides with development. We describe environmental and genetic
      factors that can influence the production of secondary metabolites. In the case
      of the filamentous fungus Aspergillus nidulans, we review the only described work
      that genetically links the sporulation of this fungus to the production of the
      mycotoxin sterigmatocystin through a shared G-protein signaling pathway.

PMID- 12209000
TI  - Evolutionary conservation of reactions in translation.
AB  - Current X-ray diffraction and cryoelectron microscopic data of ribosomes of
      eubacteria have shed considerable light on the molecular mechanisms of
      translation. Structural studies of the protein factors that activate ribosomes
      also point to many common features in the primary sequence and tertiary structure
      of these proteins. The reconstitution of the complex apparatus of translation has
      also revealed new information important to the mechanisms. Surprisingly, the
      latter approach has uncovered a number of proteins whose sequence and/or
      structure and function are conserved in all cells, indicating that the mechanisms
      are indeed conserved. The possible mechanisms of a new initiation factor and two
      elongation factors are discussed in this context.

PMID- 12209001
TI  - Communication among oral bacteria.
AB  - Human oral bacteria interact with their environment by attaching to surfaces and
      establishing mixed-species communities. As each bacterial cell attaches, it forms
      a new surface to which other cells can adhere. Adherence and community
      development are spatiotemporal; such order requires communication. The discovery
      of soluble signals, such as autoinducer-2, that may be exchanged within
      multispecies communities to convey information between organisms has emerged as a
      new research direction. Direct-contact signals, such as adhesins and receptors,
      that elicit changes in gene expression after cell-cell contact and biofilm growth
      are also an active research area. Considering that the majority of oral bacteria
      are organized in dense three-dimensional biofilms on teeth, confocal microscopy
      and fluorescently labeled probes provide valuable approaches for investigating
      the architecture of these organized communities in situ. Oral biofilms are
      readily accessible to microbiologists and are excellent model systems for studies
      of microbial communication. One attractive model system is a saliva-coated
      flowcell with oral bacterial biofilms growing on saliva as the sole nutrient
      source; an intergeneric mutualism is discussed. Several oral bacterial species
      are amenable to genetic manipulation for molecular characterization of
      communication both among bacteria and between bacteria and the host. A successful
      search for genes critical for mixed-species community organization will be
      accomplished only when it is conducted with mixed-species communities.

PMID- 12209003
TI  - Cortical representation of first and second pain sensation in humans.
AB  - Single painful stimuli evoke two successive and qualitatively distinct sensations
      referred to as first and second pain sensation. Peripherally, the neural basis of
      this phenomenon is a dual pathway for pain with Adelta and C fibers mediating
      first and second pain, respectively. Yet, the differential cortical correlates of
      both sensations are largely unknown. We therefore used magnetoencephalography to
      record and directly compare first and second pain-related cortical responses to
      cutaneous laser stimuli in humans. Our results show that brief painful stimuli
      evoke sustained cortical activity corresponding to sustained pain perception
      comprising early first pain-related and late second pain-related components.
      Cortical activity was located in primary (S1) and secondary (S2) somatosensory
      cortices and anterior cingulate cortex. Time courses of activations disclosed
      that first pain was particularly related to activation of S1 whereas second pain
      was closely related to anterior cingulate cortex activation. Both sensations were
      associated with S2 activation. These results correspond to the different
      perceptual characteristics of both sensations and probably reflect different
      biological functions of first and second pain. First pain signals threat and
      provides precise sensory information for an immediate withdrawal, whereas second
      pain attracts longer-lasting attention and motivates behavioral responses to
      limit further injury and optimize recovery.

PMID- 12209004
TI  - CFTR chloride channels are regulated by a SNAP-23/syntaxin 1A complex.
AB  - Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs)
      mediate membrane fusion reactions in eukaryotic cells by assembling into
      complexes that link vesicle-associated SNAREs with SNAREs on target membranes (t
      SNAREs). Many SNARE complexes contain two t-SNAREs that form a heterodimer, a
      putative intermediate in SNARE assembly. Individual t-SNAREs (e.g., syntaxin 1A)
      also regulate synaptic calcium channels and cystic fibrosis transmembrane
      conductance regulator (CFTR), the epithelial chloride channel that is defective
      in cystic fibrosis. Whether the regulation of ion channels by individual t-SNAREs
      is related to SNARE complex assembly and membrane fusion is unknown. Here we show
      that CFTR channels are coordinately regulated by two cognate t-SNAREs, SNAP-23
      (synaptosome-associated protein of 23 kDa) and syntaxin 1A. SNAP-23 physically
      associates with CFTR by binding to its amino-terminal tail, a region that
      modulates channel gating. CFTR-mediated chloride currents are inhibited by
      introducing excess SNAP-23 into HT29-Cl.19A epithelial cells. Conversely, CFTR
      activity is stimulated by a SNAP-23 antibody that blocks the binding of this t
      SNARE to the CFTR amino-terminal tail. The physical and functional interactions
      between SNAP-23 and CFTR depend on syntaxin 1A, which binds to both proteins. We
      conclude that CFTR channels are regulated by a t-SNARE complex that may tune CFTR
      activity to rates of membrane traffic in epithelial cells.

PMID- 12209005
TI  - Revisiting the kinetics of nitric oxide (NO) binding to soluble guanylate
      cyclase: the simple NO-binding model is incorrect.
AB  - Soluble guanylate cyclase (sGC) is a ferrous iron hemoprotein receptor for nitric
      oxide (NO). NO binding to the heme activates the enzyme 300-fold. sGC as isolated
      is five-coordinate, ferrous with histidine as the axial ligand. The NO-activated
      enzyme is a five-coordinate nitrosyl complex where the axial histidine bond is
      broken. Past studies using rapid-reaction kinetics demonstrated that both the
      formation of a six-coordinate intermediate and the conversion of the intermediate
      to the activated five-coordinate nitrosyl complex depended on the concentration
      of NO. A model invoking a second NO molecule as a catalyst for the conversion of
      the six-coordinate intermediate to the five-coordinate sGC-NO complex was
      proposed to explain the observed kinetic data. A recent study [Bellamy, T. C.,
      Wood, J. & Garthwaite, J. (2002) Proc. Natl. Acad. Sci. USA 99, 507-510]
      concluded that a simple two-step binding model explains the results. Here we show
      through further analysis and simulations of previous data that the simple two
      step binding model cannot be used to describe our results. Instead we show that a
      slightly more complex two-step binding model, where NO is used as a ligand in the
      first step and a catalyst in the second step, can describe our results quite
      satisfactorily. These new simulations combined with the previous activation data
      lead to the conclusion that the intermediate six-coordinate sGC-NO complex has
      substantial activity. The model derived from our simulations also can account for
      the slow deactivation of sGC that has been observed in vitro.

PMID- 12209006
TI  - Ethyl pyruvate prevents lethality in mice with established lethal sepsis and
      systemic inflammation.
AB  - Sepsis, a potentially fatal clinical syndrome, is mediated by an early (e.g.,
      tumor necrosis factor and IL-1) and late [e.g., high mobility group B-1 (HMGB1)]
      proinflammatory cytokine response to infection. Specifically targeting early
      mediators has not been effective clinically, in part because peak mediator
      activity often has passed before therapy can be initiated. Late-acting downstream
      effectors, such as HMGB1, that mediate sepsis lethality may be more relevant
      therapeutic targets. Ethyl pyruvate (EP) recently was identified as an
      experimental therapeutic that significantly protects against lethal hemorrhagic
      shock. Here, we report that EP attenuates lethal systemic inflammation caused by
      either endotoxemia or sepsis even if treatment begins after the early tumor
      necrosis factor response. Treatment with EP initiated 24 h after cecal puncture
      significantly increased survival (vehicle survival = 30% vs. EP survival = 88%, P
      < 0.005). EP treatment significantly reduced circulating levels of HMGB1 in
      animals with established endotoxemia or sepsis. In macrophage cultures, EP
      specifically inhibited activation of p38 mitogen-activated protein kinase and NF
      kappaB, two signaling pathways that are critical for cytokine release. This
      report describes a new strategy to pharmacologically inhibit HMGB1 release with a
      small molecule that is effective at clinically achievable concentrations. EP now
      warrants further evaluation as an experimental "rescue" therapeutic for sepsis
      and other potentially fatal systemic inflammatory disorders.

PMID- 12209007
TI  - Chronic treatment with nitric oxide-releasing aspirin reduces plasma low-density
      lipoprotein oxidation and oxidative stress, arterial oxidation-specific epitopes,
      and atherogenesis in hypercholesterolemic mice.
AB  - The effects of chronic treatment with nitric oxide-containing aspirin (NO
      aspirin, NCX-4016) in comparison with regular aspirin or placebo on the
      development of a chronic disease such as atherosclerosis were investigated in
      hypercholesterolemic low-density lipoprotein (LDL)-receptor-deficient mice. Male
      mice were assigned randomly to receive in a volume of 10 ml/kg either placebo (n
      = 10), 30 mg/kg/day NO-aspirin (n = 10), or 18 mg/kg/day of regular aspirin (n =
      10). After 12 weeks of treatment, the computer-assisted imaging analysis revealed
      that NO-aspirin reduced the aortic cumulative lesion area by 39.8 +/- 12.3%
      compared with that of the placebo (P < 0.001). Regular aspirin did not reduce
      significantly aortic lesions (-5.1 +/- 2.3%) compared with the placebo [P =
      0.867, not significant (NS)]. Furthermore, NO-aspirin reduced significantly
      plasma LDL oxidation compared with aspirin and placebo, as shown by the
      significant reduction of malondialdehyde content (P < 0.001) as well as by the
      prolongation of lag-time (P < 0.01). Similarly, systemic oxidative stress,
      measured by plasma isoprostanes, was significantly reduced by treatment with NCX
      4016 (P < 0.05). More importantly, mice treated with NO-aspirin revealed by
      immunohistochemical analysis of aortic serial sections a significant decrease in
      the intimal presence of oxidation-specific epitopes of oxLDL (E06 monoclonal
      antibody, P < 0.01), and macrophages-derived foam cells (F4/80 monoclonal
      antibody, P < 0.05), compared with placebo or aspirin. These data indicate that
      enhanced NO release by chronic treatment with the NO-containing aspirin has
      antiatherosclerotic and antioxidant effects in the arterial wall of
      hypercholesterolemic mice.

PMID- 12209002
TI  - Microbial cellulose utilization: fundamentals and biotechnology.
AB  - Fundamental features of microbial cellulose utilization are examined at
      successively higher levels of aggregation encompassing the structure and
      composition of cellulosic biomass, taxonomic diversity, cellulase enzyme systems,
      molecular biology of cellulase enzymes, physiology of cellulolytic
      microorganisms, ecological aspects of cellulase-degrading communities, and rate
      limiting factors in nature. The methodological basis for studying microbial
      cellulose utilization is considered relative to quantification of cells and
      enzymes in the presence of solid substrates as well as apparatus and analysis for
      cellulose-grown continuous cultures. Quantitative description of cellulose
      hydrolysis is addressed with respect to adsorption of cellulase enzymes, rates of
      enzymatic hydrolysis, bioenergetics of microbial cellulose utilization, kinetics
      of microbial cellulose utilization, and contrasting features compared to soluble
      substrate kinetics. A biological perspective on processing cellulosic biomass is
      presented, including features of pretreated substrates and alternative process
      configurations. Organism development is considered for "consolidated
      bioprocessing" (CBP), in which the production of cellulolytic enzymes, hydrolysis
      of biomass, and fermentation of resulting sugars to desired products occur in one
      step. Two organism development strategies for CBP are examined: (i) improve
      product yield and tolerance in microorganisms able to utilize cellulose, or (ii)
      express a heterologous system for cellulose hydrolysis and utilization in
      microorganisms that exhibit high product yield and tolerance. A concluding
      discussion identifies unresolved issues pertaining to microbial cellulose
      utilization, suggests approaches by which such issues might be resolved, and
      contrasts a microbially oriented cellulose hydrolysis paradigm to the more
      conventional enzymatically oriented paradigm in both fundamental and applied
      contexts.

PMID- 12209008
TI  - 8-Oxoguanine rearranges the active site of human topoisomerase I.
AB  - 7,8-Dihydro-8-oxoguanine (8-oxoG) is the most common form of oxidative DNA damage
      in human cells. Biochemical studies have shown that 8-oxoG decreases the DNA
      cleavage activity of human topoisomerase I, an enzyme vital to DNA metabolism and
      stability. We present the 3.1-A crystal structure of human topoisomerase I in
      noncovalent complex with a DNA oligonucleotide containing 8-oxoG at the +1
      position in the scissile strand. We find that 8-oxoG reorganizes the active site
      of human topoisomerase I into an inactive conformation relative to the structures
      of topoisomerase I-DNA complexes elucidated previously. The catalytic Tyr-723-Phe
      rotates away from the DNA cleavage site and packs into the body of the molecule.
      A second active-site residue, Arg-590, becomes disordered and is not observed in
      the structure. The docked, inactive conformation of Tyr-723-Phe is reminiscent of
      the related tyrosine recombinase family of integrases and recombinases,
      suggesting a common regulatory mechanism. We propose that human topoisomerase I
      binds to DNA first in an inactive conformation and then rearranges its active
      site for catalysis. 8-OxoG appears to impact topoisomerase I by stabilizing the
      inactive, DNA-bound state.

PMID- 12209009
TI  - Nitrogen monoxide-mediated control of ferritin synthesis: implications for
      macrophage iron homeostasis.
AB  - Intracellular iron homeostasis is regulated posttranscriptionally by iron
      regulatory proteins 1 and 2 (IRP1 and IRP2). In the absence of iron in the labile
      pool, IRPs bind to specific nucleotide sequences called iron responsive elements
      (IREs), which are located in the 5' untranslated region of ferritin mRNA and the
      3' untranslated region of transferrin receptor mRNA. IRP binding to the IREs
      suppresses ferritin translation and stabilizes transferrin receptor mRNA, whereas
      the opposite scenario develops in iron-replete cells. Binding of IRPs to the IREs
      is also affected by nitrogen monoxide (NO), but there are conflicting reports
      regarding the effect of NO on ferritin synthesis. In this study, we demonstrated
      that a short exposure of RAW 264.7 cells (a macrophage cell line) to the NO+
      donor, sodium nitroprusside (SNP), resulted in a dramatic increase in ferritin
      synthesis. The SNP-mediated increase of ferritin synthesis could be blocked by
      MG132, an inhibitor of proteasome-dependent protein degradation, which also
      prevented the degradation of IRP2 caused by SNP treatment. Moreover, treatment of
      RAW 264.7 cells with IFN-gamma and lipopolysaccharide caused IRP2 degradation and
      stimulated ferritin synthesis, changes that could be prevented by specific
      inhibitors of inducible nitric oxide synthase. Furthermore, the SNP-mediated
      increase in ferritin synthesis was associated with a significant enhancement of
      iron incorporation into ferritin. These observations indicate that NO+-mediated
      modulation of IRP2 plays an important role in controlling ferritin synthesis and
      iron metabolism in murine macrophages.

PMID- 12209010
TI  - Position of aromatic residues in the S6 domain, not inactivation, dictates
      cisapride sensitivity of HERG and eag potassium channels.
AB  - Unintended block of HERG K+ channels is a side effect of many common medications
      and is the most common cause of acquired long QT syndrome associated with
      increased risk of life-threatening arrhythmias. The molecular mechanism of high
      affinity HERG block by structurally diverse compounds has been attributed to pi
      stacking and cation-pi interactions of a drug (e.g., cisapride) with specific
      aromatic amino acid residues (Tyr-652 and Phe-656) in the S6 alpha-helical domain
      that face the central cavity of the channel. It also has been proposed that
      strong C-type inactivation of HERG facilitates or is the primary determinant of
      high-affinity drug binding. The structurally related, but noninactivating eag
      channel is insensitive to HERG blockers unless inactivation is induced by
      specific amino acid mutations [Ficker, E., Jarolimek, W. & Brown, A. M. (2001)
      Mol. Pharmacol. 60, 1343-1348]. Here we examine the relative importance of
      inactivation vs. positioning of S6 aromatic residues in determining sensitivity
      of HERG and eag channels to block by cisapride. The repositioning of Tyr-652 or
      Phe-656 along the S6 alpha-helical domain of HERG reduced sensitivity of channels
      to block by cisapride. Moreover, independent of inactivation, repositioning of
      the equivalent aromatic residues in Drosophila eag channels induced sensitivity
      to block by cisapride. These findings suggest that positioning of S6 aromatic
      residues relative to the central cavity of the channel, not inactivation per se
      determines drug block of HERG or eag channels.

PMID- 12209011
TI  - Previously uncharacterized isoforms of divalent metal transporter (DMT)-1:
      implications for regulation and cellular function.
AB  - Divalent metal transporter 1 (DMT1) mediates apical iron uptake into duodenal
      enterocytes and also transfers iron from the endosome into the cytosol after
      cellular uptake via the transferrin receptor. Hence, mutations in DMT1 cause
      systemic iron deficiency and anemia. DMT1 mRNA levels are increased in the
      duodenum of iron-deficient animals. This regulation has been observed for DMT1
      mRNA harboring an iron-responsive element (IRE) in its 3' UTR, but not for a
      processing variant lacking a 3'UTR IRE, suggesting that the IRE regulates the
      expression of DMT1 mRNA in response to iron levels. Here, we show that iron
      regulation of DMT1 involves the expression of a previously unrecognized upstream
      5' exon (exon 1A) of the human and murine DMT1 gene. The expression of this
      previously uncharacterized 5' exon is tissue-specific and particularly prevalent
      in the duodenum and kidney. It adds an in-frame AUG translation initiation codon
      extending the DMT1 ORF by a conserved sequence of 29-31 amino acids. In
      combination with the IRE- and non-IRE variants in the 3'UTR, our results reveal
      the existence of four DMT1 mRNA isoforms predicting the synthesis of four
      different DMT1 proteins. We show that two regulatory regions, the 5'
      promoter/exon 1A region and the IRE-containing terminal exon participate in iron
      regulation of DMT1 expression, which operate in a tissue-specific way. These
      results uncover an unexpected complexity of DMT1 expression and regulation, with
      implications for understanding the physiology, cell biology, and pathophysiology
      of mammalian iron metabolism.

PMID- 12209012
TI  - A protease assay for two-photon crosscorrelation and FRET analysis based solely
      on fluorescent proteins.
AB  - GFP and the red fluorescent protein, DsRed, have been combined to design a
      protease assay that allows not only for fluorescence resonance energy transfer
      (FRET) studies but also for dual-color crosscorrelation analysis, a single
      molecule-based method that selectively probes the concomitant movement of two
      distinct tags. The measurement principle is based on a spectrally resolved
      detection of single molecules diffusing in and out of a diffraction-limited laser
      focus. Double-labeled substrate molecules are separated into two single-labeled
      products by specific cleavage at a protease cleavage site between the two
      flanking tags, DsRed and GFP, thus disrupting joint fluctuations in the two
      detection channels and terminating FRET between the two labels. In contrast to
      enzyme assays based solely on FRET, this method of dual-color crosscorrelation is
      not limited to a certain range of distances between the fluorophores and is much
      more versatile with respect to possible substrate design. To simplify the
      measurement setup, two-photon excitation was used, allowing for simultaneous
      excitation of both tags with a single infrared laser wavelength. The general
      concept was experimentally verified with a GFP-peptide-DsRed construct containing
      the cleavage site for tobacco etch virus protease. Two-photon excitation in the
      infrared and the use of cloneable tags make this assay easily adaptable to
      intracellular applications. Moreover, the combination of FRET and
      crosscorrelation analysis in a single-molecule-based approach promises exciting
      perspectives for miniaturized high-throughput screening based on fluorescence
      spectroscopy.

PMID- 12209013
TI  - MYO18B, a candidate tumor suppressor gene at chromosome 22q12.1, deleted,
      mutated, and methylated in human lung cancer.
AB  - Loss of heterozygosity on chromosome 22q has been detected in approximately 60%
      of advanced nonsmall cell lung carcinoma (NSCLC) as well as small cell lung
      carcinoma (SCLC), suggesting the presence of a tumor suppressor gene on 22q that
      is involved in lung cancer progression. Here, we isolated a myosin family gene,
      MYO18B, located at chromosome 22q12.1 and found that it is frequently deleted,
      mutated, and hypermethylated in lung cancers. Somatic MYO18B mutations were
      detected in 19% (14/75) of lung cancer cell lines and 13% (6/46) of primary lung
      cancers of both SCLC and NSCLC types. MYO18B expression was reduced in 88%
      (30/34) of NSCLC and 47% (8/17) of SCLC cell lines. Its expression was restored
      by treatment with 5-aza-2'-deoxycytidine in 11 of 14 cell lines with reduced
      MYO18B expression, and the promoter CpG island of the MYO18B gene was methylated
      in 17% (8/47) of lung cancer cell lines and 35% (14/40) of primary lung cancers.
      Furthermore, restoration of MYO18B expression in lung carcinoma cells suppressed
      anchorage-independent growth. These results indicate that the MYO18B gene is a
      strong candidate for a novel tumor suppressor gene whose inactivation is involved
      in lung cancer progression.

PMID- 12209015
TI  - Containing multitudes: focus on "novel and nondetected human signaling protein
      polymorphisms".

PMID- 12209014
TI  - Dual localization of human DNA topoisomerase IIIalpha to mitochondria and
      nucleus.
AB  - The human TOP3alpha gene encoding DNA topoisomerase IIIalpha (hTop3alpha) has two
      potential start codons for the synthesis of proteins 1,001 and 976 aa residues in
      length. The sequence of the N-terminal region of the 1,001-residue form resembles
      signal peptide sequences for mitochondrial import, and fluorescence microscopy
      shows that the addition of as few as the first 34 aa of the 1,001-residue form of
      hTop3alpha to a green fluorescent protein can direct the chimeric protein to
      mitochondria. Biochemical analyses of subcellular fractions of HeLa cells further
      demonstrate that a distinctive fraction of hTop3alpha is present inside
      mitochondria, as evidenced by its resistance to proteinase K. This fraction
      constitutes several percent of the enzyme in the nuclear fraction, suggesting
      that the distribution of the mitochondrial and nuclear forms of hTop3alpha is
      roughly in proportion to the DNA contents of these cellular compartments. The
      presence of a type IA DNA topoisomerase in the mitochondria of other eukaryotes
      is supported by an examination of the amino acid sequences of mouse and
      Drosophila DNA topoisomerase IIIalpha and Schizosaccharomyces pombe DNA
      topoisomerase III. Given the presence of at least one type IA DNA topoisomerase
      in all forms of life examined to date, the finding of a type IA enzyme in
      mitochondria further supports the notion of a key role of such enzymes in DNA
      transactions.

PMID- 12209016
TI  - Exploring genetic regulatory networks in metazoan development: methods and
      models.
AB  - One of the foremost challenges of 21st century biological research will be to
      decipher the complex genetic regulatory networks responsible for embryonic
      development. The recent explosion of whole genome sequence data and of genome
      wide transcriptional profiling methods, such as microarrays, coupled with the
      development of sophisticated computational tools for exploiting and analyzing
      genomic data, provide a significant starting point for regulatory network
      analysis. In this article we review some of the main methodological issues
      surrounding genome annotation, transcriptional profiling, and computational
      prediction of cis-regulatory elements and discuss how the power of model genetic
      organisms can be used to experimentally verify and extend the results of genomic
      research.

PMID- 12209017
TI  - Fatty acid binding protein-2 gene variants and insulin resistance: gene and gene
      environment interaction effects.
AB  - The intestinal fatty acid binding protein (FABP2) gene is proposed as a candidate
      gene for diabetes because the protein it codes is involved in fatty acid (FA)
      absorption and metabolism and may, therefore, affect insulin sensitivity and
      glucose metabolism. Numerous studies have assessed FABP2 gene variants and their
      association with insulin resistance and type 2 diabetes. Some weak evidence
      indicates that the silent variants and those in the noncoding regions of the gene
      (codon 118, 3' noncoding region, intron 2 trinucleotide repeat) might be
      associated with insulin resistance/type 2 diabetes. The most extensively studied
      variant is the missense Ala54Thr variation, which is common in diverse
      populations and results in increased FA absorption in vivo. Some evidence
      indicates that this variant may be associated with insulin sensitivity/type 2
      diabetes. However, the large majority of studies assessing the potential
      association between the Ala54Thr FABP2 variant and insulin resistance/type 2
      diabetes did not account for the independent and substantial effects of body
      composition, habitual physical activity (PA) levels, and diet on insulin
      resistance. We recently reported that there was an association between Ala54Thr
      FABP2 genotypes and insulin sensitivity after accounting for the independent
      effects of body composition and habitual PA levels on insulin sensitivity.
      Furthermore, others have demonstrated that Ala54Thr FABP2 may associate with
      insulin sensitivity, but only if individuals are consuming a high-fat diet. These
      results highlight the importance of including behavioral and environmental
      factors in the design of studies seeking to assess the impact of genes on
      physiological and clinical outcome phenotypes.

PMID- 12209018
TI  - Novel and nondetected human signaling protein polymorphisms.
AB  - The frequency of single nucleotide polymorphisms (SNPs) in downstream signaling
      proteins was determined by combination heteroduplex HPLC and double-stranded
      sequencing of genomic DNA from 96-144 congestive heart failure (CHF) patients.
      Analysis of 56 coding exons in 9 signaling genes revealed 17 novel and 8
      previously reported synonymous (no change in amino acid) SNPs, as well as one
      novel nonsynonymous SNP in the Rad small G protein. Because this initial analysis
      failed to detect numerous SNPs reported in the NCBI and Celera databases, double
      strand sequencing of relevant exons from 74-91 CHF patients was used to confirm
      the absence of 10 previously reported nonsynonymous SNPs. Our results show that
      synonymous SNPs are frequent in signaling protein genes, whereas nonsynonymous
      SNPs are rare, suggesting a high degree of evolutionary conservation among these
      downstream signaling molecules. Comparisons of our results to the NCBI and Celera
      databases indicates that 56% of their SNP entries are not detected in our cohort.
      Importantly, while 31% of database SNPs were verified, 69% of SNPs detected in
      our cohort are not included in these databases. These findings indicate that
      caution may be warranted in relying exclusively on SNP databases as catalogs for
      polymorphic signaling protein genes.

PMID- 12209019
TI  - Comparison of different labeling methods for two-channel high-density microarray
      experiments.
AB  - In this report we evaluate three methods for labeling nucleic acids to be
      hybridized to a cDNA microarray: direct labeling, indirect amino-allyl labeling,
      and the dendrimer labeling method (Genisphere). The dendrimer method requires the
      smallest quantity of sample, 2.5 microg of total RNA compared with 20 microg with
      the direct or indirect methods. Therefore, we wanted to know whether the
      performance of the dendrimer method is comparable to the other methods, or
      whether significant information is lost. Performance can be considered in terms
      of sensitivity, dynamic range, and reproducibility of the quantitative signals
      for gene intensity. We compared the three labeling methods by generating three
      sets of eight self-to-self hybridizations using the same total RNA sample in all
      cases ("replicate study"). In our analysis, we controlled for the effects of
      print-tip and background subtraction biases. We also performed a smaller study,
      namely, a dilution series study with five dilution points per labeling method, to
      evaluate one aspect of predictive ability. From the replicate study, the
      dendrimer method appeared to perform as well, and often better, with respect to
      reproducibility and ability to detect expression. However, in the dilution series
      study, this method was outperformed by the other two in terms of predictive
      ability and did not perform very well. These findings are helping to guide our
      decisions on what labeling method to use for subsequent studies, based on the
      purpose of a specific study and its limitations in terms of available material.

PMID- 12209020
TI  - Influence of age, sex, and strength training on human muscle gene expression
      determined by microarray.
AB  - The purpose of this study was to determine the influence of age, sex, and
      strength training (ST) on large-scale gene expression patterns in vastus
      lateralis muscle biopsies using high-density cDNA microarrays and quantitative
      PCR. Muscle samples from sedentary young (20-30 yr) and older (65-75 yr) men and
      women (5 per group) were obtained before and after a 9-wk unilateral heavy
      resistance ST program. RNA was hybridized to cDNA filter microarrays representing
      approximately 4,000 known human genes and comparisons were made among arrays to
      determine differential gene expression as a result of age and sex differences,
      and/or response to ST. Sex had the strongest influence on muscle gene expression,
      with differential expression (>1.7-fold) observed for approximately 200 genes
      between men and women (approximately 75% with higher expression in men). Age
      contributed to differential expression as well, as approximately 50 genes were
      identified as differentially expressed (>1.7-fold) in relation to age,
      representing structural, metabolic, and regulatory gene classes. Sixty-nine genes
      were identified as being differentially expressed (>1.7-fold) in all groups in
      response to ST, and the majority of these were downregulated. Quantitative PCR
      was employed to validate expression levels for caldesmon, SWI/SNF (BAF60b), and
      four-and-a-half LIM domains 1. These significant differences suggest that in the
      analysis of skeletal muscle gene expression issues of sex, age, and habitual
      physical activity must be addressed, with sex being the most critical variable.

PMID- 12209021
TI  - A novel SCN5A mutation associated with long QT-3: altered inactivation kinetics
      and channel dysfunction.
AB  - Mutations in the gene (SCN5A) encoding the alpha-subunit of the cardiac Na+
      channel cause congenital long QT syndrome (LQT-3). Here we describe a novel LQT-3
      mutation I1768V (I1768V) located in the sixth transmembrane spanning segment of
      domain IV. This mutation is unusual in that it is located within a transmembrane
      spanning domain and does not promote the typically observed sustained inward
      current corresponding to a gain of channel function (bursting). Rather, I1768V
      increases the rate of recovery from inactivation and increases the channel
      availability, observed as a positive shift of the steady-state inactivation curve
      (+7.6 mV). Using a Markovian model of the cardiac Na+ channel, we simulated these
      changes in gating behavior and demonstrated that a small increase in the rate of
      recovery from inactivation is sufficient to explain all of the experimentally
      observed current changes. The effect of these alterations in channel gating
      results in an increase in window current that may act to disrupt cardiac
      repolarization.

PMID- 12209022
TI  - Reciprocal rat chromosome 2 congenic strains reveal contrasting blood pressure
      and heart rate QTL.
AB  - Evidence exists implying multiple blood pressure quantitative trait loci (QTL) on
      rat chromosome 2. To examine this possibility, four congenic strains and nine
      substrains were developed with varying size chromosome segments introgressed from
      the spontaneously hypertensive rat (SHR/lj) and normotensive Wistar-Kyoto rat
      (WKY/lj) onto the reciprocal genetic background. Cardiovascular phenotyping was
      conducted with telemetry over extended periods during standard salt (0.7%) and
      high-salt (8%) diets. Our results are consistent with at least three independent
      pressor QTL: transfer of SHR/lj alleles to WKY/lj reveals pressor QTL within
      D2Rat21-D2Rat27 and D2Mgh10-D2Rat62, whereas transfer of WKY/lj D2Rat161-D2Mit8
      to SHR/lj reveals a depressor locus. Our results also suggest a depressor QTL in
      SHR/lj located within D2Rat161-D2Mgh10. Introgressed WKY/lj segments also reveal
      a heart rate QTL within D2Rat40-D2Rat50 which abolished salt-induced bradycardia,
      dependent upon adjoining SHR/lj alleles. This study confirms the presence of
      multiple blood pressure QTL on chromosome 2. Taken together with our other
      studies, we conclude that rat chromosome 2 is rich in alleles for cardiovascular
      and behavioral traits and for coordinated coupling between behavior and
      cardiovascular responses.

PMID- 12209023
TI  - Smooth muscle expression of Cre recombinase and eGFP in transgenic mice.
AB  - We report the generation of transgenic mice designed to facilitate the study of
      vascular and nonvascular smooth muscle biology in vivo. The smooth muscle myosin
      heavy chain (smMHC) promoter was used to direct expression of a bicistronic
      transgene consisting of Cre recombinase and enhanced green fluorescent protein
      (eGFP) coding sequences. Animals expressing the transgene display strong
      fluorescence confined to vascular and nonvascular smooth muscle. Enzymatic
      dissociation of smooth muscle yields viable, fluorescent cells that can be
      studied as single cells or sorted by FACS for gene expression studies.
      smMHC/Cre/eGFP mice were crossed with ROSA26/lacZ reporter mice to determine Cre
      recombinase activity; Cre recombinase was expressed in all smooth muscles in
      adult mice, and there was an excellent overlap between expression of the
      recombinase and eGFP. Initial smooth muscle-specific expression of fluorescence
      and Cre recombinase was detected on embryonic day 12.5. These mice will be useful
      to define smooth muscle gene function in vivo in mice, for the study of gene
      function in single, live cells, and for the determination of gene expression in
      vascular and nonvascular smooth muscle.

PMID- 12209024
TI  - Eyewitness testimony.
AB  - The criminal justice system relies heavily on eyewitness identification for
      investigating and prosecuting crimes. Psychology has built the only scientific
      literature on eyewitness identification and has warned the justice system of
      problems with eyewitness identification evidence. Recent DNA exoneration cases
      have corroborated the warnings of eyewitness identification researchers by
      showing that mistaken eyewitness identification was the largest single factor
      contributing to the conviction of these innocent people. We review major
      developments in the experimental literature concerning the way that various
      factors relate to the accuracy of eyewitness identification. These factors
      include characteristics of the witness, characteristics of the witnessed event,
      characteristics of testimony, lineup content, lineup instructions, and methods of
      testing. Problems with the literature are noted with respect to both the relative
      paucity of theory and the scarcity of base-rate information from actual cases.

PMID- 12209025
TI  - Human-computer interaction: psychological aspects of the human use of computing.
AB  - Human-computer interaction (HCI) is a multidisciplinary field in which psychology
      and other social sciences unite with computer science and related technical
      fields with the goal of making computing systems that are both useful and usable.
      It is a blend of applied and basic research, both drawing from psychological
      research and contributing new ideas to it. New technologies continuously
      challenge HCI researchers with new options, as do the demands of new audiences
      and uses. A variety of usability methods have been developed that draw upon
      psychological principles. HCI research has expanded beyond its roots in the
      cognitive processes of individual users to include social and organizational
      processes involved in computer usage in real environments as well as the use of
      computers in collaboration. HCI researchers need to be mindful of the longer-term
      changes brought about by the use of computing in a variety of venues.

PMID- 12209026
TI  - The early education of socioeconomically disadvantaged children.
AB  - This chapter reviews selected research on the education of low-socioeconomic
      status (SES) children from birth through the first years of elementary school.
      Themes include the importance of early academic skills and interest to later
      achievement; the benefits of integrating knowledge from research on mental health
      and other areas; the need to utilize and build children's strengths as well as
      address their weaknesses; and a call to connect research to practice and policy.
      Relevant research on race and culture is reviewed because ethnic minority low-SES
      children are at great risk of poverty. Gender is discussed because low-SES boys
      have poorer general achievement than girls, while very few low-SES girls pursue
      careers in math- and science-related fields.

PMID- 12209027
TI  - Postgraduate education in rheumatology.

PMID- 12209028
TI  - Prevention of vascular damage in scleroderma with angiotensin-converting enzyme
      (ACE) inhibition.
AB  - Great strides have been made in identifying and managing the organ-based
      complications of systemic sclerosis (SSc). There is no room for the nihilism
      towards treating this disease that used to be so prevalent. However, there is
      still relatively little hard evidence on which to base treatment decisions.
      Previous trials have been constrained by the low disease prevalence and the
      difficulty in recruiting sufficient patients especially with disease of recent
      onset. The results of past trials have often been confounded by the failure to
      recognize the marked heterogeneity of SSc and the inclusion of patient subsets
      with widely varying disease expression, course and outcome. It is recognized that
      progress will only be made in this area with coordinated multicentre studies. As
      a result, national and international networks of clinicians with expertise in the
      management of SSc have been formed. In the UK, the Systemic Sclerosis Study Group
      has established a national scleroderma register and, together with the
      Scleroderma Special Interest Group of the British Society for Rheumatology (BSR),
      a multicentre base for therapeutic studies. As a result of developments in our
      understanding of the pathogenesis of scleroderma and our ability to subset
      patients more effectively, a number of rather more rational approaches to
      treating the disease and its complications are being tested. In parallel with
      this, considerable progress is being made in developing universally agreed
      measures of disease activity and severity and in identifying surrogate laboratory
      markers of disease activity that are relevant to therapeutic studies. These
      multicentre trials need substantial funding and often do not attract support from
      the pharmaceutical industry. It was because of the difficulty in financing long
      term, multicentre studies in uncommon conditions that the ARC/BSR Clinical Trials
      Programme was established. The QUINS trial, which is funded by this Programme, is
      described here as an example of one of several therapeutic protocols being
      developed by the UK Systemic Sclerosis Study Group that are currently being
      tested in multicentre trials. Contact details are provided in the appendix for
      clinicians who are interested in registering patients on the UK Scleroderma
      Register or participating in this or in the other therapeutic studies.

PMID- 12209029
TI  - Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage.
AB  - Destruction of articular joints occurs progressively in patients with rheumatoid
      arthritis (RA). Although the exact aetiology of RA has not been fully elucidated,
      a large body of evidence supports a role for interleukin-1 (IL-1) in cartilage
      and bone erosion. In vitro studies suggest that IL-1 can cause cartilage
      destruction by stimulating the release of matrix metalloproteinases and other
      degradative products, and it can increase bone resorption by stimulating
      osteoclast differentiation and activation. In animal models of RA, blocking the
      effects of IL-1 with either IL-1 receptor antagonist (IL-1Ra; endogenous), anti
      IL-1 monoclonal antibodies, or soluble IL-1 type II receptors significantly
      reduced cartilage destruction and bone erosion. Gene therapy with IL-1Ra was also
      effective in reducing joint destruction in experimental RA and osteoarthritis
      (OA) models. In clinical studies, anakinra, a human recombinant IL-1 receptor
      antagonist (IL-1ra; exogenous), significantly slowed radiographic progression of
      RA relative to placebo and significantly reduced clinical symptoms when used as
      monotherapy or in addition to existing methotrexate therapy. These results
      demonstrate that blocking IL-1 protects bone and cartilage from progressive
      destruction in RA.

PMID- 12209031
TI  - Increased levels of autoantibodies against copper-oxidized low density
      lipoprotein, malondialdehyde-modified low density lipoprotein and cardiolipin in
      patients with rheumatoid arthritis.
AB  - OBJECTIVES: To analyse the association of autoantibodies against cardiolipin (CL)
      and oxidized low density lipoproteins [copper-oxidized low density lipoprotein
      (oxLDL), malondialdehyde-modified LDL (MDA-LDL)] with rheumatoid arthritis (RA)
      and cardiovascular complications. METHODS: One hundred and twenty-one patients
      with RA were consecutively included. Autoantibodies were determined by ELISA.
      Healthy individuals from the same region were used as controls. RESULTS: Levels
      of IgG, IgM and IgA antibodies against MDA-LDL and CL, as well as IgG and IgA
      antibodies against oxLDL were increased in the patients (P<0.01). The prevalence
      of IgG, IgM and IgA antibodies against CL was higher than in the normal
      population (74, 82 and 14%, respectively). The prevalence of IgG and IgA
      antibodies against oxLDL was also significantly increased (35 and 25%,
      respectively) and so was the prevalence of IgG and IgM antibodies against MDA-LDL
      (17 and 26%, respectively) compared with controls. The levels of IgM and IgA
      antibodies against aCL and IgM against MDA-LDL were increased in patients with
      extra-articular manifestations. Patients who developed myocardial infarction had
      a higher prevalence of IgG antibodies against MDA-LDL (P=0.04). There were
      substantial correlations between the levels of antibodies against oxLDL, MDA-LDL
      and CL. CONCLUSIONS: RA patients had increased levels and prevalence of
      autoantibodies against CL, oxLDL and MDA-LDL, with associations to severity of
      disease and cardiovascular complications.

PMID- 12209030
TI  - Retrospective analysis of outcome in a cohort of patients with lupus nephritis
      treated between 1977 and 1999.
AB  - OBJECTIVE: To review the development, histological type and outcome of a cohort
      of patients with lupus nephritis who were managed and followed up by the
      specialist Bloomsbury Rheumatology Unit between 1977 and 1999. PATIENTS AND
      METHODS: Seventy-eight of the 280 (28%) patients with systemic lupus
      erythematosus (SLE) developed nephritis. Occurrence of end stage renal disease
      (ESRD) according to World Health Organization (WHO) class was analysed, and
      patients were subdivided according to whether treatment included at least six
      pulses of intravenous (i.v.) cyclophosphamide (CYC) once a month. RESULTS: For
      patients with WHO class III nephritis, three out of five treated with i.v. CYC
      developed ESRD compared with none out of 10 not treated with i.v. CYC (P < 0.02).
      There was no significant difference between these subgroups in terms of a variety
      of parameters with good prognostic value, except anti-dsDNA titre at time of
      biopsy (which was greater in the former). For patients with WHO class IV
      nephritis, three out of 16 treated with i.v. CYC developed ESRD, compared with
      five out of 20 not treated with i.v. CYC (no significant difference). CONCLUSION:
      These data suggest that there may be a subgroup of patients with lupus nephritis
      (WHO class III) whose long-term outcome is not adversely affected by the omission
      of i.v. CYC.

PMID- 12209032
TI  - Serum concentrations of cartilage oligomeric matrix protein, fibrinogen and
      hyaluronan distinguish inflammation and cartilage destruction in experimental
      arthritis in rats.
AB  - OBJECTIVES: We investigated if changes in serum/plasma fibrinogen (FIB),
      hyaluronan (HA) and cartilage oligomeric matrix protein (COMP) levels can be used
      to differentiate between inflammation and cartilage involvement during arthritis.
      METHODS: Collagen-induced arthritis (CIA), oil-induced arthritis (OIA) and for
      comparison, experimental autoimmune encephalitis (EAE) induced in DA rats were
      investigated. RESULTS: Elevations of FIB concentrations were apparent at days 4-7
      post-immunization in both arthritis models reaching a maximum on day 20-21, i.e.
      before peak arthritis. Elevations of HA in both models were seen shortly before
      macroscopically apparent arthritis, and peaked at or just before maximal
      arthritis, i.e. later in CIA than in OIA. COMP levels increased only after onset
      of arthritis and peaked late in disease (days 34-37), being significantly higher
      in the more destructive CIA compared with the less destructive OIA. During EAE
      flares, only FIB levels increased. CONCLUSIONS: FIB is a general inflammation
      marker, HA appears to be a marker for synovitis and changes in COMP levels appear
      to reflect the cartilage destruction process.

PMID- 12209033
TI  - Health status in patients awaiting hip replacement for osteoarthritis.
AB  - BACKGROUND: Hip osteoarthritis is a major cause of pain and disability,
      especially in the elderly. As part of a study investigating factors that could be
      associated with advanced osteoarthritis of the hip, we compared the health status
      of patients awaiting arthroplasty for hip osteoarthritis with controls. We
      further investigated the interaction of hip osteoarthritis with other variables
      (age, gender, social class and concurrent pain) in relation to health status.
      METHODS: A case-control study was performed in two English health districts
      (Portsmouth and North Staffordshire) during 1993-1995. A total of 611 patients
      (210 men and 401 women) listed for hip replacement because of osteoarthritis over
      an 18-month period formed the case group and were compared with an equal number
      of controls selected from the general population and individually matched for
      age, gender and general practice. Cases and controls completed a structured
      interviewer-administered questionnaire, which included queries about their
      medical condition, occupation (from which a measure of social class was derived),
      and general health status using the SF36. RESULTS: Physical function (t=32.1,
      P<0.001), social function (t=16.8, P<0.001) and perceived general health (t=4.1,
      P<0.001) were worse in the case group, but energy/vitality and mental health
      showed little difference between cases and controls. Cases were more likely to
      report knee pain than controls, but case-control status was not associated with
      pain in the fingers or shoulders, or with social class. However, differences in
      physical and social function between cases and controls did vary with socio
      demographic factors and concurrent knee pain status. CONCLUSION: Patients
      awaiting hip-replacement because of osteoarthritis were more likely to be
      restricted in their physical and social life than adults in the general
      population, but mental state and vitality appear unimpaired in this group. This
      contrasts with findings from other chronic pain disorders. Manual social class is
      not linked to being on a waiting list for osteoarthritic hip replacement but does
      add to the burden on health status, particularly social functioning in those with
      osteoarthritis of the hip.

PMID- 12209034
TI  - Efficacy and safety of valdecoxib in treating the signs and symptoms of
      rheumatoid arthritis: a randomized, controlled comparison with placebo and
      naproxen.
AB  - OBJECTIVE: To compare the efficacy of the COX-2 specific inhibitor valdecoxib
      with the conventional NSAID naproxen and placebo in treating rheumatoid arthritis
      (RA). METHODS: This multi-centre, randomized, double-blind, placebo-controlled
      trial compared the efficacy and safety of valdecoxib 10 mg (n=209), 20 mg (n=212)
      or 40 mg once daily (q.d.) (n=221) with naproxen 500 mg b.i.d. (n=226) or placebo
      (n=222), in treating the signs and symptoms of RA. Efficacy was assessed by the
      number of patients responding to treatment according to the American College of
      Rheumatology-Responder Index (ACR-20). RESULTS: ACR-20 response was recorded for
      all randomized patients who received a single dose of study medication (above).
      Valdecoxib, at all administered doses, produced significant improvements in the
      ACR-20 Responder Index at weeks 2, 6 and 12 compared with placebo (P<or=0.01).
      Valdecoxib and naproxen did not differ in terms of ACR-20 response rate and the
      three doses of valdecoxib were similar to one another. All three doses of
      valdecoxib were well tolerated. CONCLUSIONS: Single daily doses of valdecoxib 10,
      20 and 40 mg demonstrated efficacy that was superior to placebo and similar to
      naproxen in treating the signs and symptoms of RA. All three doses provided
      similar levels of efficacy.

PMID- 12209035
TI  - Importance of species-specific antigens in the serodiagnosis of Chlamydia
      trachomatis reactive arthritis.
AB  - OBJECTIVES: To determine the most sensitive and specific method of anti-Chlamydia
      antibody measurement for the serodiagnosis of Chlamydia trachomatis reactive
      arthritis. METHODS: Immunoblotting, enzyme-linked immunosorbent assays using six
      synthetic peptides or recombinant antigens and a microimmunofluorescence test
      were used to determine the presence of IgG, IgM and IgA in serum samples from 17
      patients with C. trachomatis reactive arthritis. Twenty patients with other
      inflammatory arthropathies without evidence of urogenital C. trachomatis
      infection were used as controls. RESULTS: The best association of sensitivity
      (76%) and specificity (85%) was obtained when IgG and/or IgA reactivity to two
      species-specific antigens was determined. These antigens were synthetic peptides,
      derived from species-specific epitopes in the variable domain IV of the major
      outer membrane protein (MOMP) (Labsystems, Finland) and recombinant polypeptide
      encoded by open reading frame 3 of the plasmid (pgp3). CONCLUSIONS: IgG and/or
      IgA anti-MOMP-derived peptides and anti-pgp3 could be useful for the diagnosis of
      probable C. trachomatis reactive arthritis.

PMID- 12209036
TI  - A regional audit of the prevention and treatment of corticosteroid-induced
      osteoporosis in patients with rheumatic diseases in the West Midlands.
AB  - BACKGROUND: Audit is an important tool in clinical governance. Combining
      resources from across a region may facilitate data collection and allow variation
      in practice between individual units to be analysed. This audit is the first such
      regional audit to be carried out in rheumatology in the West Midlands and the
      organization and value of regional audit is discussed. This audit assessed the
      prevention and management of corticosteroid-induced osteoporosis (CIOP). METHODS:
      Adult patients attending rheumatology follow-up clinics in 10 units, during a 2
      week period were assessed using the 1998 National Osteoporosis Society (NOS)
      guidance on the prevention and management of CIOP. The audit standard adopted was
      that 80% of eligible patients should be on appropriate therapy. RESULTS: Data was
      collected on 1766 (95.2%) of 1855 patients during the audit period. Two hundred
      and thirty-five (13.3%) were currently being prescribed or about to commence
      >or=7.5 mg daily of oral prednisolone for >or=6 months. Dual X-ray absorptiometry
      scans were performed in 102 patients (43.4%). Of these, 53 (52%) had a T score of
      -1.5 or below at the hip or spine. Of the 235 patients, 202 (86%) were receiving
      osteoporosis treatment. One hundred and forty-eight patients (63%) were receiving
      appropriate osteoporosis medication according to the NOS 1998 guidelines and 87
      (37%) were inappropriately treated. Of these, 71 (81.6%) were under-treated and
      16 (18.4%) were over-treated. CONCLUSIONS: Overall, the Region failed to meet the
      audit standard. The audit highlighted a number of differences and potential
      problems in the West Midlands with regard to CIOP which are currently being
      addressed by individual units and the West Midlands Rheumatology Services and
      Training Committee (WMRSTC). The Committee plan to re-audit in 2 yr.

PMID- 12209037
TI  - The role of interleukin-10 promoter polymorphisms in the clinical expression of
      primary Sjogren's syndrome.
AB  - OBJECTIVE: To analyse the role of polymorphisms of the interleukin-10 promoter
      region in the epidemiologic, clinical and immunologic characteristics of patients
      with primary Sjogren's syndrome (SS). METHODS: Sixty-three consecutive patients
      (59 women and four men; mean age 57 yr; range 20-83 yr) were studied in our Unit.
      All patients fulfilled four or more of the modified diagnostic criteria for SS
      proposed by the European Community Study Group in 1996. As controls, 150 healthy
      volunteers were recruited from the medical and laboratory staff working in our
      hospital. All the samples from patients and controls were analysed by PCR
      amplification and direct sequencing. RESULTS: The frequency of the interleukin-10
      (IL-10) GCC haplotype was higher (0.48 vs 0.34, P=0.006) and the frequency of the
      IL-10 ACC haplotype lower (0.25 vs 0.39, P=0.005) in patients with primary SS
      compared with healthy controls. In the genotype analysis, the frequency of the
      GCC/ATA genotype was higher (29 vs 11%, P=0.001) and that of the ACC/ACC genotype
      lower (3 vs 12%, P=0.044) in patients with primary SS compared with healthy
      controls. GCC-carriers showed an earlier onset of the disease (48.06+/-14.98 yr
      vs 57.53+/-14.20 yr, P=0.034). The existence of systemic involvement (defined by
      cutaneous vasculitis, peripheral neuropathy, renal and/or pulmonary involvement)
      was more frequent in carriers of the GCC haplotype, although the difference did
      not reach statistical significance (40 vs 27%, P=0.278). No significant
      differences in the haematologic (hypergammaglobulinaemia, elevated ESR) and
      immunologic (ANA, RF, anti-Ro/SS-A and anti-La/SS-B antibodies) parameters were
      observed in carriers of the GCC haplotype. CONCLUSION: We describe an abnormal
      distribution of IL-10 promoter haplotypes in patients with primary SS compared
      with healthy controls. This consists of a predominance of the GCC haplotype,
      mainly related to a higher frequency of the heterozygote haplotype GCC/ATA. The
      presence of the GCC haplotype does not originate a different immunologic pattern
      but leads to an earlier onset of primary SS.

PMID- 12209038
TI  - Adrenaline-induced immunological changes are altered in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate whether in rheumatoid arthritis (RA) patients the
      immunological changes induced by adrenaline are different from healthy controls
      (HC). METHODS: Fifteen female RA patients and 14 HC were infused with 1 micro
      g/kg adrenaline over 20 min. Blood was drawn before, immediately after, and 1 h
      after the end of infusion. Lymphocyte subpopulations, cytokine production and
      natural killer cell cytotoxicity were determined. RESULTS: Subjects exhibited
      mild cardiovascular changes with no differences between patients and controls.
      CD16(+)CD56(+)CD3(-) NK cells increased by a factor of 5.7, CD3(+) T cells by
      1.5, monocytes by 1.6 and PMN by 1.2 in both groups. The numbers of IL-8- and IL
      10-producing monocytes were higher in patients and presented a larger increase
      after infusion. NK cytotoxic activity was higher in RA patients and increased
      after infusion in both groups. Activated monocytes and T cells were
      preferentially recruited in patients and controls. Values returned to baseline 1
      h later. CONCLUSION: We describe an altered response to adrenaline in patients
      with RA with both pro- and anti-inflammatory effects. Additionally, activated T
      cells and monocytes recruited to the peripheral blood may influence disease
      activity.

PMID- 12209039
TI  - Inflammatory myositis associated with anti-U1-small nuclear ribonucleoprotein
      antibodies: a subset of myositis associated with a favourable outcome.
AB  - OBJECTIVES: Inflammatory myositides are rare chronic disorders which may be
      either isolated or associated with other conditions such as connective tissue
      diseases or neoplasia. A large variety of autoantibodies can be detected in
      patients with myositis, some of which have a diagnostic and/or a prognostic
      value. Myositis associated with anti-U1-small nuclear ribonucleoprotein
      antibodies (anti-U1-snRNP Abs) are usually considered as overlapping syndromes,
      mainly mixed connective tissue diseases (MCTD) in which muscle symptoms occur
      insidiously during the disease course and are characterized by a favourable
      outcome. METHODS: The clinical, biological, immunological and pathological
      findings as well as the outcome of five patients with anti-U1-snRNP-associated
      myositis were retrospectively analysed. RESULTS: Patients were mainly black
      females. In all five patients, myositis was the predominant manifestation at
      presentation. Associated conditions consisted of interstitial lung disease (ILD)
      (three), arthritis (three) and neurological symptoms (two). No patient presented
      Raynaud's phenomenon nor met criteria for MCTD. Biological inflammatory features,
      rheumatoid factor and polyclonal hypergammaglobulinaemia were present in all
      cases. Besides anti-U1-snRNP Abs, one patient had anti-Ro/SSA and anti-La/SSB Abs
      at presentation and one additional patient developed anti-double-stranded-DNA and
      anti-Sm Abs after a follow-up of more than 4 yr. No patient had anti-PM/sclerosis
      (Scl) nor anti-aminoacyl-tRNA synthetase Abs. All patients dramatically improved
      with steroids, and reached complete remission (CR) within 3 weeks. Two patients
      relapsed 18 months after CR. They both reached rapidly second CR using steroids
      associated or not with oral methotrexate. CONCLUSION: Our data suggest that anti
      U1-snRNP Abs may define a subset of myositis characterized by a favourable
      outcome, though often associated with ILD and/or neurological manifestations.

PMID- 12209040
TI  - Does active treatment of rheumatoid arthritis limit disease-associated bone loss?
AB  - OBJECTIVE: Generalized bone loss in rheumatoid arthritis (RA) is multi-factorial,
      with the inflammatory disease itself thought to contribute to bone loss. To study
      the extent to which control of disease activity affects bone turnover in RA and
      whether treatment with disease-modifying anti-rheumatic drugs (DMARDs) reduces
      bone turnover and loss of bone mass, we measured bone density and biochemical
      markers of bone resorption in a group of patients with active RA starting on
      DMARDS. METHODS: Patients with active RA were enrolled on starting a new DMARD.
      Patients were mobile and none took steroids or any treatment for osteoporosis.
      Clinical and laboratory measures of disease activity were made at 3-monthly
      intervals and an index of disease activity (DAS) calculated. Bone density was
      assessed at 0, 1 and 2 yr (Hologic QDR 4500c). Urinary deoxypyridinoline (D-PYR)
      and pyridinoline (PYR) were measured by ELISA at 0, 3, 6, 9 and 12 months.
      RESULTS: Forty patients were enrolled, mean age 59.5 (range 31-76), 26 female, 14
      male, 25 had established RA, 15 had RA for <2 yr. Baseline D-PYR was elevated
      (8.4+/-4.55 nmol/mmol creatinine) and correlated with ESR (r=0.6, P<0.01) and DAS
      (r=0.4, P<0.05). On treatment ESR and DAS fell by 38.5 and 29.3%, respectively. D
      PYR was reduced by 12.3% by 9 months (P<0.01). Spearman rank order correlation
      showed ESR to be the most significant determinant of D-PYR over 1 yr (r=0.43,
      P<0.001). Serial bone density was available on 21 patients. There was no
      significant change in BMD over the 2 yr. The change in DAS over 0-3 months showed
      an inverse relationship with the percent change in spine over 1 yr (r=-0.5,
      P=0.05). The change in D-PYR over 0-3 months was not closely related to the
      change in BMD at hip or spine at 1 yr. CONCLUSION: Disease activity is a
      significant determinant of bone turnover in RA. Bone resorption markers fall on
      treatment of RA with DMARDs and no change in BMD was demonstrated at 2 yr. This
      study suggests the need to control disease activity in RA in order to prevent
      systemic bone loss.

PMID- 12209042
TI  - Specialist training in rheumatology in Europe.
AB  - Rheumatology is a broad discipline managing a spectrum of different conditions
      and there are divergences in what is routinely treated by rheumatologists both
      within and between countries. The free movement of doctors throughout the
      European Community has lead to moves to harmonize specialist training to ensure
      common standards of care. The Union Europeene des Medecins Specialistes (UEMS)
      has developed recommendations for the specialist training of rheumatologists in
      Europe that recognizes the broad definition of the discipline and the diversity
      of clinical practice in Europe. The core curriculum aims to provide a common
      standard around which to develop locally applicable national curricula. The
      provision of high quality care requires some assessment of training and
      competency as well as continuing professional development and ways of ensuring
      the provision of this throughout the European Community to a mutually high
      standard are being developed. The future may see more overlap in the training of
      all the disciplines concerned with the management of those with musculoskeletal
      conditions to their benefit.

PMID- 12209041
TI  - Results of a randomized, dose-ranging trial of etoricoxib in patients with
      osteoarthritis.
AB  - OBJECTIVES: To evaluate the clinical efficacy and tolerability of etoricoxib in
      the treatment of osteoarthritis (OA) of the knee and define the clinically active
      dose range for further clinical trials. METHODS: This two-part, randomized,
      double-blind, placebo- and active comparator-controlled trial was conducted in
      617 adults with knee OA. In Part 1 (6 weeks), patients received placebo,
      etoricoxib 5, 10, 30, 60 or 90 mg q.d. In Part 2 (8 weeks), patients received
      etoricoxib 30, 60 or 90 mg q.d. or diclofenac 50 mg t.i.d., predetermined at Part
      1 allocation. Efficacy and safety were evaluated. Primary efficacy end-points
      were the Western Ontario and McMaster's University Osteoarthritis Index (WOMAC)
      Pain subscale, Patient Global Assessment of Response to Therapy, and Investigator
      Global Assessment of Disease Status. RESULTS: At 6 weeks, etoricoxib 5, 10, 30,
      60 and 90 mg each demonstrated clinical efficacy superior to placebo. Maximal
      efficacy was seen with 60 mg. In Part 2, etoricoxib 30, 60 and 90 mg were
      generally similar to diclofenac. Patients receiving etoricoxib 30, 60 or 90 mg in
      Parts I and II had sustained effects over 14 weeks. All treatments were well
      tolerated. CONCLUSIONS: Etoricoxib 60 mg once daily showed maximal efficacy in
      treating OA in this study. Etoricoxib 5-90 mg once daily was generally well
      tolerated in OA patients for up to 14 weeks.

PMID- 12209043
TI  - Recurrent tenosynovitis in Sweet's syndrome.

PMID- 12209044
TI  - Back pain.

PMID- 12209045
TI  - Hydrotherapy has had and has a rationale.

PMID- 12209046
TI  - A possible novel mechanism of opportunistic infection in systemic lupus
      erythematosus, based on a case of toxoplasmic encephalopathy.

PMID- 12209047
TI  - Do patients receive appropriate information and treatment following bone mineral
      density measurements?

PMID- 12209048
TI  - Bilateral recurrent focal myositis of gastrocnemius muscles after BCG
      vaccination.

PMID- 12209049
TI  - Robin goodfellow.

PMID- 12209051
TI  - Computational biology.

PMID- 12209052
TI  - Bayesian network approach to cell signaling pathway modeling.
AB  - The modeling of cellular signaling pathways is an emerging field. Sachs et al.
      illustrate the application of Bayesian networks to an example cellular pathway
      involving the activation of focal adhesion kinase (FAK) and extracellular signal
      regulated kinase (ERK) in response to fibronectin binding to an integrin. They
      describe how to use the analysis to select from among proposed models, formulate
      hypotheses regarding component interactions, and uncover potential dynamic
      changes in the interactions between these components. Although the data sets
      currently available for this example problem are too small to definitively point
      to a particular model, the approach and results provide a glimpse into the power
      that these methods will achieve once the technology for obtaining the necessary
      data becomes readily available.

PMID- 12209053
TI  - Modeling the cell's guidance system.
AB  - Cell locomotion can be directed by external gradients of diffusible substances
      leading to chemotaxis. Recently, the mechanisms of gradient sensing, the cell
      guidance system, came under scrutiny both in experimental analysis and
      computational modeling. Here, we review several recent computational models of
      gradient sensing in eukaryotic cells, demonstrating why some of them predict
      little sensitivity to changes in the gradient and response "locking," whereas
      others predict high gradient sensitivity at the expense of signal gain. We also
      propose a way to view chemotaxis regulation as a highly coupled combination of
      semi-independent control modules, leading to simplifying modeling of this complex
      cellular behavior.

PMID- 12209054
TI  - Surprise! HRT and the WHI.

PMID- 12209055
TI  - Should newborn nursery viewing windows be eliminated? Writing for the PRO
      position.

PMID- 12209056
TI  - Should newborn nursery viewing windows be eliminated? Writing for CON position.

PMID- 12209057
TI  - Airbags & children: making correct choices in child passenger restraints.
AB  - Countless numbers of young lives are lost each year due to motor vehicle crashes.
      One of the most effective means of reducing the number of children killed and
      injured as occupants in motor vehicles is through the use of child passenger
      restraints. Seat belts and child safety seats save lives and reduce the severity
      of injuries sustained by occupants in motor vehicle crashes. Nurses are in a
      unique position to educate and influence families on the proper way to safely
      transport all motor vehicle passengers. Therefore, nurses working with infants,
      children, and families have a moral and professional obligation to understand the
      basics of child passenger safety. At the very least, nurses should be able to
      direct families appropriately for specifics related to child passenger
      restraints. The intent of this article is to provide an overview of child
      passenger safety through a historical, theoretical, and clinical approach. Proper
      child restraint use is reviewed based on current recommendations for age and
      size. The potential hazards of child restraint misuse, with an in-depth
      discussion on airbags, is presented. The discussion on airbags serves to dispel
      any misconceptions that may be held about airbags. The article includes two case
      studies that illustrate the injury potential of relatively common misuse
      patterns. The clinical implications for maternal-child nurses include the
      recognition that child passenger deaths are primarily due to child restraint
      nonuse and misuse and the realization of nursing's role in the promotion of
      proper child passenger restraint.

PMID- 12209058
TI  - Oral health during pregnancy.
AB  - The purpose of this article is to explore how poor oral health affects pregnancy
      and to review current recommendations for dental care during pregnancy. While
      nurses are concerned with numerous aspects of the health of pregnant women, the
      health of maternal and fetal dentition may be overlooked. However, due to recent
      findings that periodontal disease may be a risk factor for preterm low
      birthweight, nurses and other maternal healthcare providers are becoming more
      aware of oral health during pregnancy. It is important to understand that
      establishing a healthy oral environment is the most important objective in
      planning the dental care for the pregnant patient. This objective is achieved by
      adequate plaque control (brushing and flossing) and professional prophylaxis
      including coronal scaling, root planing, and polishing. Nurses, nurse
      practitioners, and nurse-midwives should include assessment of maternal dentition
      and referral for dental problems as part of their prenatal practice. Patients
      should be encouraged to schedule elective dental treatment during the second
      trimester but seek prompt care for acute dental problems. Teaching related to
      oral health during pregnancy should include the importance of proper nutrition to
      ensure maternal and fetal oral health, including taking prenatal vitamins and
      eating foods high in protein, calcium, phosphorus, and vitamins A, C, and D.
      Potential teratogens that may be encountered during dental care should also be
      discussed. Nurses can be vital in improving perinatal outcomes and maternal/fetal
      dental health through screening, referral, and education of their pregnant
      clients.

PMID- 12209059
TI  - Theoretical perspectives of postpartum depression and their treatment
      implications.
AB  - Approximately 13% of new mothers experience postpartum depression. This crippling
      mood disorder wreaks havoc not only on the mothers themselves but also on their
      entire families. Between 25% and 50% of mothers with postpartum depression have
      episodes lasting 6 months or longer. The most significant factor in the duration
      of the postpartum depression is the length of delay to adequate treatment. The
      purpose of this article is to describe five different theoretical perspectives of
      postpartum depression and the interventions for treatment derived from each: the
      medical model, feminist theory, attachment theory, interpersonal theory, and self
      labeling theory. Crucial to clinicians' choice of treatment of postpartum
      depression is the theoretical lens they use to view this devastating mood
      disorder. Nursing implications derived from these theoretical perspectives are
      addressed.

PMID- 12209060
TI  - Paradigms for assessment: women's knowledge and skill attainment.
AB  - This article describes two models of assessment that nurses can use with women
      throughout their life span: (1) knowledge attainment (Belenky, Clinchy,
      Goldberger, & Tarule, 1986) and (2) skill attainment (Dreyfus & Dreyfus, 1996).
      These models consider each woman's unique reality, acknowledging that how she
      experiences pregnancy and postpartum is based on how she has lived her life. Her
      integration of experiences, coping strategies, and life events may be the
      foundation upon which she will incorporate the new experiences of pregnancy and
      motherhood. Using these models can help provide the maternal-child nurse with a
      blueprint for the development of appropriate care plans and teaching plans.

PMID- 12209061
TI  - Using evidence to educate birthing center nursing staff about infant states,
      cues, and behaviors.
AB  - The authors sought to apply evidence from research to nursing practice. Research
      about infant states, cues, and behaviors was presented to a birthing center
      nursing staff and expectant parent class instructors. Posttest results indicated
      that the staff's knowledge and skill in interpreting infant behavior for parents
      increased after an educational session. The results are important, for research
      supports the idea that parent-infant attachment affects both parents and infants
      by promoting a loving relationship and improved infant development, a healthy
      self-image, and better relationships later in life. Cue sensitivity has been
      documented as the origin of parent-infant attachment. Cue sensitivity involves
      recognition of individualized infant body language and provision of an
      appropriate response. Parents who are sensitive to their infant's needs and who
      respond consistently and appropriately foster a mutually satisfying reciprocal
      interaction that leads to a healthy relationship. Incorporating information about
      infant states, cues, and behaviors into prenatal education can provide parents
      with an introduction to quality parent-child interactions.

PMID- 12209062
TI  - Finding information about quality healthcare on the Internet: www.ahcpr.gov.

PMID- 12209066
TI  - Myocardial dilemma.

PMID- 12209068
TI  - After the fall. 9/11's Effects on New York's EMS personnel extend far beyond
      symptoms of post-traumatic stress. It's been a recovery derailed by lacking
      support systems & quashed by the absence of local & national recognition for EMS
      efforts & losses.

PMID- 12209069
TI  - Teach with style. Integrate individual learning styles with teaching methods to
      enhance student learning.

PMID- 12209070
TI  - Selective spinal immobilization. The use of assessment criteria & protocols to
      select patients who don't require complete spinal immobilization.

PMID- 12209071
TI  - COPD vs. CHF. Use history & physical exam clues to differentiate & treat two
      significant medical emergencies.

PMID- 12209075
TI  - From friend to foe.

PMID- 12209078
TI  - Anaphylaxis: a review of causes and mechanisms.
AB  - Anaphylaxis is a life-threatening syndrome resulting from the sudden release of
      mast cell- and basophil-derived mediators into the circulation. Foods and
      medications cause most anaphylaxis for which a cause can be identified, but
      virtually any agent capable of directly or indirectly activating mast cells or
      basophils can cause this syndrome. This review discusses the pathophysiologic
      mechanisms of anaphylaxis, its causes, and its treatment.

PMID- 12209079
TI  - Oxidative stress in allergic respiratory diseases.
AB  - There is ample evidence that allergic disorders, such as asthma, rhinitis, and
      atopic dermatitis, are mediated by oxidative stress. Excessive exposure to
      reactive oxygen and nitrogen species is the hallmark of oxidative stress and
      leads to damage of proteins, lipids, and DNA. Oxidative stress occurs not only as
      a result of inflammation but also from environmental exposure to air pollution
      and cigarette smoke. The specific localization of antioxidant enzymes in the lung
      and the rapid reaction of nitric oxide with reactive oxygen species, such as
      superoxide, suggest that antioxidant enzymes might also function as cell
      signaling agents or regulators of cell signaling. Therapeutic interventions that
      decrease exposure to environmental reactive oxygen species or augment endogenous
      antioxidant defenses might be beneficial as adjunctive therapies for allergic
      respiratory disorders.

PMID- 12209080
TI  - Smallpox vaccination: Risk considerations for patients with atopic dermatitis.
AB  - As the threat of bioterrorism with pathogenic microbes such as smallpox virus
      (Variola major) increases, the question of widespread voluntary vaccination with
      smallpox (vaccinia) vaccines is being carefully considered. A major challenge
      lies in the ability to protect the population from the disease while minimizing
      the considerable side effects from the vaccine. Individuals with active or
      quiescent atopic dermatitis are at increased risk for vaccinia complications. The
      nature of these complications and other considerations are summarized in this
      rostrum.

PMID- 12209082
TI  - Exercise in elite summer athletes: Challenges for diagnosis.
AB  - BACKGROUND: There is a high prevalence of asthma and exercise-induced
      bronchoconstriction (EIB) in elite athletes when the diagnosis is based on
      symptoms and medication use. Objective measurements are now required by some
      sporting bodies to support a diagnosis of asthma or EIB to justify use of beta
      agonists. Such measurements could include bronchial provocation with
      methacholine, with eucapnic voluntary hyperpnea (EVH) of dry air (a surrogate for
      exercise), or both. OBJECTIVE: The aim of the study was to investigate the
      relationship between asthma symptoms and responses to methacholine and the EVH
      challenge in a group of unselected elite summer-sport athletes. The outcome would
      be to inform practitioners of a suitable objective approach to identifying those
      with asthma and EIB. METHODS: Fifty elite summer-sport athletes with or without
      asthma were recruited from sporting teams and sports medicine centers throughout
      Melbourne, Australia. All subjects completed a respiratory questionnaire and, on
      separate days, underwent a bronchoprovocation challenge test with methacholine
      and EVH. RESULTS: Forty-two subjects reported one or more respiratory symptoms in
      the past year, 9 had positive methacholine challenge results (mean PD(20) of 1.69
      +/- 2.05 micromol), and 25 had positive EVH challenge results (mean fall in
      FEV(1) of 25.4% +/- 15%). Although all subjects with positive methacholine
      challenge results had positive EVH challenge results, methacholine had a negative
      predictive value of only 61% and a sensitivity of 36% for identifying those
      responsive to EVH. CONCLUSION: These findings suggest that the pathogenesis of
      EIB in elite athletes might be different from that of asthma, and as such,
      neither symptoms nor the methacholine challenge test should be used exclusively
      for identifying EIB.

PMID- 12209081
TI  - Proteasome-dependent regulation of Syk tyrosine kinase levels in human basophils.
AB  - BACKGROUND: In human basophils, FcepsilonRI signal initiation, leading to
      histamine release, relies on activation of Syk protein tyrosine kinase. Basophils
      from approximately 10% of unselected donors do not degranulate in response to
      FcepsilonRI cross-linking. Their unresponsiveness has been linked to the absence
      of Syk protein despite apparently normal levels of Syk mRNA. OBJECTIVE: The aim
      of this study was to explore pathways of Syk protein degradation as a possible
      posttranslational mechanism for downregulating Syk protein levels in human
      basophils and other leukocytes. METHODS: Highly purified basophils, lymphocytes,
      and monocytes were incubated in the presence or absence of a panel of cell
      permeable inhibitors of proteolytic degradation pathway(s). Subsequently, the
      protein level of Syk tyrosine kinase was determined by means of Western blotting.
      In vitro assays were conducted through use of immunoprecipitated basophil Syk and
      a rabbit reticulocyte lysate system. RESULTS: Three inhibitors of proteasome
      mediated degradation-PSI, lactacystin, and ALLN-substantially increased Syk
      levels in releaser basophils and restored Syk expression in nonreleaser
      basophils. Caspase inhibitors were less effective, and inhibitors of calpain
      mediated proteolysis had no effect. Among other leukocytes tested, only naive
      CD4(+) T cells had more Syk after proteasome inhibitor treatment. In vitro
      ubiquitination assays demonstrated that Syk is readily ubiquitinated in vitro and
      also that Syk ubiquitination is associated with a substantial decrease in total
      levels of Syk protein. CONCLUSION: These data provide evidence for a
      ubiquitin/proteasome-dependent mechanism that contributes to Syk regulation in
      human basophils and might also be relevant to naive T cells. Understanding this
      regulatory pathway might lead to strategies for suppressing allergic inflammation
      while preserving essential Syk-mediated functions in other hematopoietic cells.

PMID- 12209083
TI  - Hay fever and asthma in relation to markers of infection in the United States.
AB  - BACKGROUND: The hygiene hypothesis proposes that declining exposure to infections
      is implicated in the rising trend of allergy and asthma. OBJECTIVE: We sought to
      test this hypothesis by examining the relationship of hay fever, asthma, and
      atopic sensitization with markers of infection in a large general population
      sample of the United States. METHODS: We analyzed the data of 33,994 US residents
      recorded in a public database of a nationally representative cross-sectional
      survey (Third National Health and Nutrition Examination Survey, 1988-1994). The
      variables examined were sociodemographic information, lifetime diagnosis and age
      at first diagnosis of hay fever or asthma, current skin sensitization to 9
      airborne allergens and peanut, and current serology for Toxoplasma gondii, herpes
      simplex viruses type 1 and 2, and hepatitis A, B, and C viruses. RESULTS: Hay
      fever (adjusted odds ratio, 0.27; 95% CI, 0.18-0.41; P <.001) and asthma
      (adjusted odds ratio, 0.45; 95% CI, 0.31-0.66; P <.001) were less frequent in
      subjects seropositive for hepatitis A virus (HAV), T gondii, and herpes simplex
      virus 1 versus seronegative subjects after adjusting for age, sex, race, urban
      residence, census region, family size, income, and education. Skin sensitization
      to peanut and to all the airborne allergens examined, except for cockroach, was
      less frequent among HAV-seropositive versus HAV-seronegative subjects younger
      than 40 years of age. The prevalence of hay fever and asthma diagnosed at or
      before 18 years of age in HAV-seronegative subjects increased progressively from
      2.7% (95% CI, 0.7%-4.7%) and 0.4% (95% CI, 0.1%-1.6%), respectively, in cohorts
      born before 1920 to 8.5% (95% CI, 7.3%-9.7%) and 5.8% (95% CI, 4.8%-6.8%),
      respectively, in cohorts born in the 1960s, whereas they remained constant at
      around 2% in all cohorts of HAV-seropositive subjects. CONCLUSION: In the United
      States serologic evidence of acquisition of certain infections, mainly food-borne
      and orofecal infection, is associated with a lower probability of having hay
      fever and asthma. Third National Health and Nutrition Examination Survey data
      support the hypothesis that hygiene is a major factor contributing to the
      increase in hay fever, asthma, and atopic sensitization in westernized countries.

PMID- 12209084
TI  - Bronchial hyperresponsiveness induced by chronic treatment with albuterol: Role
      of sensory nerves.
AB  - BACKGROUND: It has recently been suggested that regular treatment with racemic
      beta(2)-adrenoceptor agonists might result in bronchial hyperresponsiveness (BHR)
      to a range of spasmogens, and this might be due to adverse effects of the
      distomer. OBJECTIVE: We sought to determine whether BHR induced by means of
      continuous exposure to racemic and S-albuterol was mediated by sensory nerves.
      METHODS: Naive or ovalbumin-sensitized guinea pigs were treated for 10 days with
      RS-, R-, or S-albuterol (1 mg.kg(-1).d(-1)) through subcutaneously implanted
      minipumps. Lung function was then determined in response to a number of
      spasmogens and assessed on the basis of an increase in total airway resistance. A
      separate group of animals were chronically treated with capsaicin (80 mg/kg)
      before the albuterol treatment. RESULTS: Treatment with RS- or S-albuterol
      increased airway responsiveness to bradykinin, leukotriene C(4), and capsaicin in
      naive guinea pigs (P <.05) and to histamine and ovalbumin in immunized guinea
      pigs (P <.05). Chronic treatment with capsaicin prevented the development of RS-
      and S-albuterol-induced BHR in these models. The bronchodilator efficacy of acute
      intravenously administered RS-albuterol was unaffected in RS-, R-, or S-albuterol
      treated guinea pigs compared with in vehicle-treated animals. CONCLUSION: We have
      provided evidence demonstrating that continuous exposure to RS- and S-albuterol
      increases bronchial responsiveness to a range of stimuli, an effect not
      attributed to beta-adrenoceptor occupancy or desensitization. Furthermore,
      capsaicin-sensitive sensory nerves mediate the development of BHR, at least in
      part.

PMID- 12209085
TI  - Nocturnal awakening caused by asthma in children with mild-to-moderate asthma in
      the childhood asthma management program.
AB  - BACKGROUND: Nocturnal symptoms of asthma are a cause of significant morbidity and
      are included as a central feature in the categorization of asthma severity.
      OBJECTIVES: Data from the Childhood Asthma Management Program were used to
      estimate the prevalence of nocturnal awakenings in 1041 children with mild-to
      moderate asthma and to investigate the relationships between awakenings and peak
      flows, severity of asthma, and allergen sensitivity and exposure. METHODS: Daily
      diary care data were recorded during a 28-day interval in the Childhood Asthma
      Management Program screening process. The data on morning and evening peak flows,
      overall symptom codes, albuterol use for symptoms, and nocturnal awakenings for
      asthma symptoms were analyzed and compared with measures of personal
      characteristics, pulmonary function, and environmental characteristics of the
      patients. RESULTS: Three hundred fifty-one (33.7%) children experienced 1 or more
      night awakenings caused by asthma during the 28-day screening period while not
      taking any maintenance medications. Greater risk of night awakening was
      associated with more severe asthma (greater responsiveness to bronchodilator,
      airway reactivity to methacholine, peak flow variability, and use of albuterol
      for symptoms, all P <.0001) and atopy (increased IgE and allergy skin test
      reactivity, both P =.0002). Those with a positive skin test response to dog and a
      high level of dog allergen in the home had a greater risk of night awakening
      caused by asthma (P =.01), as did those with a positive skin test response to cat
      and a high level of cat allergen in the home (P =.04). Mean daily symptom code
      and use of albuterol for asthma symptoms increased in the 3 days immediately
      before a single awakening compared with in the 4 to 6 days before the awakening
      (P =.02 and P =.01, respectively); however, both morning and evening peak flows
      as a percentage of personal best were similar in both intervals. Mean daily
      symptom code and daily use of albuterol were greater in the 3 days after an
      awakening than in the 3 days before (P <.0001 and P =.0002, respectively). Mean
      evening peak flow percentage of personal best the day after an episode of
      awakening was lower when a second consecutive awakening occurred than when there
      was only a single awakening (P =.01). CONCLUSIONS: Nocturnal awakening occurred
      in one third of the children with mild-to-moderate asthma during a month of
      relative stability and appears to be an indicator of asthma that is becoming
      increasingly severe.

PMID- 12209086
TI  - Plasma concentration of thymus and activation-regulated chemokine is elevated in
      childhood asthma.
AB  - BACKGROUND: Thymus and activation-regulated chemokine (TARC) is responsible for
      the trafficking of T(H)2 lymphocytes into sites of allergic inflammation. Serum
      TARC levels correlate with the severity of atopic dermatitis. The relationship
      between this marker and the occurrence and severity of asthma has not been
      evaluated. OBJECTIVE: We tested whether plasma TARC level is a useful marker for
      asthma and atopy in children. METHODS: Plasma total IgE levels were measured by
      means of microparticle immunoassay, and specific IgE levels to common
      aeroallergens were measured by using a fluorescent enzyme immunoassay. We used a
      sandwich enzyme immunoassay to measure plasma TARC concentrations. RESULTS: Sixty
      asthmatic children and 28 age- and sex-matched control subjects were recruited,
      with mean logarithmic plasma total IgE levels of 2.66 +/- 0.60 kIU/L and 1.74 +/-
      0.58 kIU/L, respectively (P <.0001). The median plasma TARC concentration was
      higher in asthmatic patients without inhaled corticosteroid treatment (131.0
      pg/mL) compared with those seen in steroid-treated patients (97.5 pg/mL) and
      control subjects (76.0 pg/mL; P =.01 and P <.0001, respectively). Plasma TARC
      concentration was found to correlate with total IgE level in plasma (r = 0.219, P
      =.04). This marker was also increased in subjects who were sensitized to cat
      allergen (P =.001) but not in subjects sensitized to other aeroallergens. Disease
      severity score, FEV(1) value, and atopy were not associated with increased plasma
      TARC levels. CONCLUSION: Our results suggest that plasma TARC concentrations are
      elevated in childhood asthma. This marker is also linked to plasma total IgE
      levels and cat allergen sensitization.

PMID- 12209087
TI  - Association of IFNG gene polymorphism with asthma in the Indian population.
AB  - Epidemiologic studies in India show that the prevalence of asthma is increasing,
      but no genetic studies have been reported on the Indian population thus far. We
      selected the IFNG locus on 12q21 as a candidate gene for asthma on the basis of
      its role in pathophysiology and positive linkage demonstrated in other
      populations. The aim of this study was to investigate association of a CA-repeat
      marker in this gene with asthma and total serum IgE levels in the North Indian
      population. The repeat region was PCR-amplified from patients and control
      subjects and analyzed through use of GeneScan. The distributions of allele sizes
      were found to be significantly different between patients and control subjects
      (Kolmogorov-Smirnov test, P < 10(-6)). Alleles 10 and 11 were found to be
      overrepresented in individuals with asthma, whereas alleles 13 and 15 were less
      likely in asthmatic individuals. We found that the CA-repeat polymorphism in the
      IFNG gene was significantly associated with total serum IgE levels (ANOVA, P <
      10(-4) for control subjects and P =.0036 for patients). Furthermore, a previously
      reported promoter polymorphism at the -333 base pair position was not detected in
      our population. This is the first report on the association of a candidate gene
      with asthma from the Indian subcontinent.

PMID- 12209088
TI  - Optimized conjugation ratios lead to allergen immunostimulatory
      oligodeoxynucleotide conjugates with retained immunogenicity and minimal
      anaphylactogenicity.
AB  - BACKGROUND: Immunotherapy has gradually fallen out of favor for the treatment of
      many allergic diseases because of the overall convenience, safety, and efficacy
      of medications. However, investigations suggest that allergen/immunostimulatory
      sequence oligodeoxynucleotide (ISS-ODN) conjugates (AICs) might have improved
      safety and efficacy compared with allergen extracts. OBJECTIVE: We determined
      whether changes in the ISS-ODN conjugation ratio would effect the immunogenicity
      and allergenicity of AIC. METHODS: Immunogenicity was determined by means of AIC
      vaccination of mice, followed by analysis of antigen-specific antibody and
      cytokine responses. The allergenicity of AIC was determined in mast cell release
      studies and in murine models of anaphylaxis and the Arthus reaction. RESULTS: AIC
      induced a stronger immune response than allergen alone or allergen mixed with ISS
      ODN, but higher-level ISS-ODN conjugation reduced its immunogenicity modestly. In
      mast cell degranulation studies AIC was approximately 100-fold less allergenic
      than native allergen, with stepwise increases in the ODN conjugation ratio
      leading to stepwise decreases in allergenicity. In anaphylaxis studies death
      rates were reduced from 100% with native allergen challenge to as low as 0% with
      high-ratio ISS-ODN AIC challenge. Similar results were obtained in an Arthus
      reaction model. CONCLUSION: These investigations establish that AIC is both
      significantly more immunogenic and less allergenic than native allergens and the
      techniques used might have further utility for the standardization and
      optimization of AIC formulations for use in allergic patients.

PMID- 12209089
TI  - CD40-mediated p38 mitogen-activated protein kinase activation is required for
      immunoglobulin class switch recombination to IgE.
AB  - BACKGROUND: Signaling through CD40 activates multiple kinases and signal pathways
      that drive diverse CD40-mediated biologic functions. The specific pathways
      activated by CD40 signaling involving CD40-dependent Ig class switch
      recombination (CSR) have not been defined. OBJECTIVE: We sought to dissect CD40
      activated signaling required for CD40-mediated Ig CSR by using the specific
      signal pathway inhibitors, with the emphasis on CD40-activated p38 mitogen
      activated protein kinase (p38 MAPK) signaling in CD40-mediated CSR to IgE.
      METHODS: Human B cells were costimulated with IL-4 plus anti-CD40 in the presence
      or absence of specific signal pathway inhibitors. Ig production, kinase
      phosphorylation, IgH epsilon germline transcripts and Smu-Sepsilon recombination
      were examined, and their relationships were analyzed. RESULTS: CD40-dependent IgE
      induction was inhibited by the specific p38 MAPK inhibitor SB203580 but not by
      the extracellular signal-regulated protein kinase-specific inhibitor PD98059 or
      the phosphatidylinositol 3-kinase-specific inhibitor LY294002. CD40 activation of
      p38 MAPK correlated with CD40-dependent IgE production, and IgE suppression by
      SB203580 correlated with the inhibition of CD40-activated p38 MAPK
      phosphorylation. Suppression of IgE production by SB203580 was not due to
      inhibition of cell proliferation because SB203580 did not suppress IL-4 plus
      alpha-CD40-induced cell proliferation. SB203580, but neither PD98059 nor
      LY294002, inhibited CD40-dependent Smu-Sepsilon recombination, as determined by
      using a digestion circularization PCR assay. The inhibitory effects of SB203580
      on IgE production and Smu-Sepsilon recombination were directly related to its
      ability to suppress production of Ig epsilon germline transcripts. CONCLUSION:
      These results demonstrate that p38 MAPK is required for CD40-mediated class
      switching to IgE.

PMID- 12209090
TI  - The IL1A genotype associates with atopy in nonasthmatic adults.
AB  - BACKGROUND: The skin prick test is used to examine specific IgE-mediated allergic
      responses. Generally, results accord well with anamnestic information on atopy.
      Several genetic factors probably affect the strength of allergen-mediated skin
      test reactions. OBJECTIVE: We sought to investigate skin test findings in a
      population-based sample of adult asthmatic patients and control subjects and to
      establish whether the IL1A genotype affects allergy testing. METHODS: We analyzed
      the single G-to-T base exchange polymorphism in exon 5 at +4845 of the gene
      encoding IL-1alpha (IL1A) in adult asthmatic patients (n = 245) and nonasthmatic
      control subjects (n = 405). The data were assessed for correlation with data on
      the skin test responses of these subjects to 22 common allergens. RESULTS: The
      IL1A genotype distribution and allele frequencies proved similar in patients and
      control subjects. Surprisingly, the IL1A genotype distribution was markedly
      different in control subjects with positive (ie, >/=1 positive reaction) and
      negative skin test responses (P =.006). This difference was caused by an increase
      in the frequency of the rarer allele 2 in control subjects with negative skin
      test responses (P =.004). CONCLUSION: Our study demonstrates that the IL1 gene
      complex is involved in the regulation of IgE-mediated atopic reactions. The
      results suggest that skin test responses to specific allergens are differently
      regulated in nonasthmatic and asthmatic subjects. Because of the potential role
      of the IL1A genotype as a confounding factor in skin prick testing, these results
      require special attention and should be further evaluated in other clinical
      settings.

PMID- 12209091
TI  - IgE to Bet v 1 and profilin: cross-reactivity patterns and clinical relevance.
AB  - BACKGROUND: Individuals with pollen allergy often have IgE against plant-derived
      foods. This can be due to cross-reactive IgE against Bet v 1 and homologues,
      profilins, and/or cross-reactive carbohydrate determinants. OBJECTIVE: The aim of
      this study was to correlate sensitization to Bet v 1 and profilin with individual
      recognition patterns to plant foods and clinical relevance. METHODS: Fifty-two
      patients with pollen allergy and IgE against at least one plant-derived food were
      included in the study. Adverse reactions to plant-derived foods were documented
      by using standardized interviews. Skin prick tests were performed for pollen
      (grass, birch, and mugwort) and 14 plant-derived foods. In addition, recombinant
      (r) Bet v 1 and rBet v 2 (profilin) were tested intracutaneously. Specific IgE
      against the abovementioned allergens were determined by means of RAST. Cross
      reactivity was studied by means of RAST inhibition. RESULTS: Eighty-five percent
      of patients were sensitized to Bet v 1, and 71% were sensitized to profilin.
      Profilin was associated with a higher number of positive RAST results to plant
      derived foods than Bet v 1. In contrast, Bet v 1 was associated with more
      positive skin prick test responses and more food-related symptoms. Sensitization
      to Bet v 1 was associated with IgE against apple, hazelnut, and peach, whereas
      sensitization to profilin was associated with positive RAST results to all
      investigated plant-derived foods except apple, peach, and melon. CONCLUSIONS: IgE
      antibodies against Bet v 1 have a more limited spectrum of cross-reactivity than
      those against profilin, but they frequently give rise to clinically relevant
      cross-reactivities to food. In analogy to anticarbohydrate IgE, cross-reactive
      IgE against food profilins have no or very limited clinical relevance.

PMID- 12209092
TI  - CD40 engagement enhances eosinophil survival through induction of cellular
      inhibitor of apoptosis protein 2 expression: Possible involvement in allergic
      inflammation.
AB  - BACKGROUND: CD40 engagement enhances eosinophil survival, suggesting a role for
      this receptor in the development of eosinophilia. OBJECTIVE: We examined whether
      CD40 enhances eosinophil survival by inducing the expression of antiapoptotic
      proteins. Three members of the inhibitor of apoptosis protein (IAP) family,
      namely cellular (c)-IAP1, c-IAP2, and XIAP, and 2 antiapoptotic proteins of the
      Bcl-2 family, namely Bcl-x(L) and Bfl-1/A1, were investigated. METHODS: Blood and
      sputum were obtained from healthy subjects and atopic asthmatic patients. Blood
      eosinophils were isolated by means of magnetic selection. Expression of CD40,
      IAPs, and Bcl-2 proteins was investigated by using flow cytometry,
      immunoblotting, or both. CD40 stimulation was achieved with agonistic antibodies
      or soluble ligands. Apoptosis was assessed by staining with propidium iodide and
      FITC-conjugated annexin-V. c-IAP2 expression was inhibited with antisense
      oligonucleotides. RESULTS: Freshly isolated eosinophils from healthy and
      asthmatic patients did not express CD40. Conversely, eosinophils expressed CD40
      spontaneously when cultured for 48 hours. At this time point, CD40 stimulation
      significantly delayed eosinophil apoptosis. Inhibition of eosinophil apoptosis
      was accompanied by induction of c-IAP2 but not c-IAP1, XIAP, Bcl-x(L), or Bfl
      1/A1 expression. Antisense knockdown of c-iap2 abolished CD40-induced enhancement
      of eosinophil survival. Sputum cells from asthmatic patients, unlike those from
      healthy subjects, substantially expressed CD40 and c-IAP2. Moreover, a strong
      correlation was found between the percentage of eosinophils in the sputum from
      asthmatic patients and the sputum level of CD40 and c-IAP2 expression.
      CONCLUSION: The results demonstrate that CD40 engagement enhances eosinophil
      survival through induction of c-IAP2 expression and suggest a role for this
      mechanism in allergic inflammation.

PMID- 12209093
TI  - Polyclonal and allergen-induced cytokine responses in adults with asthma:
      resolution of asthma is associated with normalization of IFN-gamma responses.
AB  - BACKGROUND: Atopic disease is associated with skewing of immune responses away
      from a T(H)1 toward a T(H)2 profile. Previous studies have implicated this
      cytokine imbalance in the development of disease. However, it is not known
      whether normalization of this imbalance is conversely associated with disease
      resolution. OBJECTIVE: To further delineate the role of reduced T(H)1 and
      increased T(H)2 cytokine production in the pathogenesis of atopic disease and to
      determine whether disease resolution is associated with alteration of cytokine
      profiles, we investigated cytokine responses in a cohort of adult patients with
      asthma followed from childhood. METHODS: A cohort of wheezy children and control
      subjects aged 7 to 10 years were recruited from 1964 to 1967. Subjects were
      reevaluated every 7 years to monitor the outcome of childhood asthma. At the 42
      year follow-up, 89 subjects from this cohort were evaluated for mitogen and house
      dust mite (HDM)-induced T(H)1 (IFN-gamma) and T(H)2 (IL-4, IL-5, and IL-13)
      cytokine responses. Cytokine responses were compared in patients with ongoing
      asthma, patients with resolved asthma, and control subjects. RESULTS: Patients
      with severe ongoing asthma had significantly reduced HDM-induced IFN-gamma
      production compared with that of control subjects and patients with resolved
      asthma. In contrast, HDM-induced IFN-gamma production in patients with resolved
      asthma was equivalent to that seen in control subjects. Patients with ongoing and
      resolved asthma produced significantly higher levels of IL-5 in response to HDM
      compared with that seen in control subjects, with levels being equivalent in
      patients with active and resolved asthma. HDM-induced IL-13 production was
      significantly increased in the patients with resolved asthma when compared with
      that seen in the control subjects. PHA-induced cytokine responses did not
      parallel HDM-induced responses. CONCLUSION: Patients with persistent and severe
      atopic asthma have a reduced HDM-induced T(H)1 response, whereas those with
      resolved asthma do not. This suggests that reduced HDM-induced IFN-gamma
      production might be an important factor contributing to ongoing severe asthma and
      that normalization of allergen-induced T(H)1 responses might be important for
      disease resolution. The finding that all subjects with a history of asthma
      displayed increased HDM-induced T(H)2 (IL-5 and IL-13) cytokine responses,
      irrespective of the presence or absence of asthma, suggests that increased T(H)2
      responses reflect the presence of the atopic state per se rather than being
      specifically linked to asthma.

PMID- 12209094
TI  - Characterization of PGE2 receptor subtypes in human eosinophils.
AB  - Although previous pharmacologic studies have indicated that PGE receptors are
      expressed in human eosinophils, the exact distribution of the subtypes remains
      mostly unknown. By using a combination of genetic and conventional pharmacologic
      approaches, coexpression of mRNAs encoding the PGE receptor 2 (EP2) and EP4 was
      confirmed in eosinophils. Moreover, competitive PCR analysis of eosinophil RNA
      revealed that levels of the EP4 receptor mRNA were significantly higher than
      those of the EP2 receptor mRNA (P =.04). On the basis of the expression levels of
      mRNAs, an EP4 agonist, but not an EP2 agonist, was effective in inducing cyclic
      AMP production in eosinophils, suggesting that the EP4 receptor is of primary
      importance in eosinophil functions of PGE(2).

PMID- 12209095
TI  - CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway
      hyperreactivity and inflammation.
AB  - BACKGROUND: T(H)2 cells play a critical role in the pathogenesis of asthma, but
      the precise immunologic mechanisms that inhibit T(H)2 cell function in vivo are
      not well understood. OBJECTIVE: The purpose of our studies was to determine
      whether T cells producing IL-10 regulate the development of asthma. METHODS: We
      used gene therapy to generate ovalbumin-specific CD4 T-helper cells to express IL
      10, and we examined their capacity to regulate allergen-induced airway
      hyperreactivity. RESULTS: We demonstrated that the CD4 T-helper cells engineered
      to express IL-10 abolished airway hyperreactivity and airway eosinophilia in
      BALB/c mice sensitized and challenged with ovalbumin and in SCID mice
      reconstituted with ovalbumin-specific T(H)2 effector cells. The inhibitory effect
      of the IL-10-secreting T-helper cells was accompanied by the presence of
      increased quantities of IL-10 in the bronchoalveolar lavage fluid, was antigen
      specific, and was reversed by neutralization of IL-10. Moreover, neutralization
      of IL-10 by administration of anti-IL-10 mAb in mice sensitized and challenged
      with ovalbumin seriously exacerbated airway hyperreactivity and airway
      inflammation. CONCLUSION: Our results demonstrate that T cells secreting IL-10 in
      the respiratory mucosa can indeed regulate T(H)2-induced airway hyperreactivity
      and inflammation, and they strongly suggest that IL-10 plays an important
      inhibitory role in allergic asthma.

PMID- 12209096
TI  - Regulation of human basophil adhesion to endothelium under flow conditions:
      Different very late antigen 4 regulation on umbilical cord blood-derived and
      peripheral blood basophils.
AB  - BACKGROUND: Although soluble mediators released by basophils in tissue sites
      contribute to the chronic injury that occurs in hypersensitivity diseases, only
      limited information is available about how circulating basophils are recruited to
      tissues. In particular, the interaction of basophils with endothelium under
      conditions that mimic physiologic flow has not been explored. OBJECTIVE: We
      sought to identify adhesion molecules regulating the attachment of human
      basophils to IL-4-activated human umbilical vein endothelial cells (HUVECs) under
      flow conditions. METHODS: A parallel-plate flow chamber and blocking mAbs were
      used to define the adhesion molecules involved in the interactions of peripheral
      blood basophils (PBBs) and cord blood-derived basophils (CBDBs) with IL-4
      activated HUVECs and with Chinese hamster ovary (CHO) cell transfectants
      expressing specific adhesion molecules. A fluorescent ligand specific for very
      late antigen 4 (VLA-4) was used to directly examine the VLA-4 affinity state of
      basophils. RESULTS: Flowing PBBs and CBDBs attached to activated HUVECs and to
      CHO cells expressing P- or E-selectin. However, only CBDBs attached to vascular
      cell adhesion molecule 1 (VCAM-1)-transfected CHO cells under flow conditions.
      The attachment of CBDBs to CHO cells was blocked by mAbs directed against E
      selectin, P-selectin, and VCAM-1, whereas attachment of PBBs was blocked by E
      selectin and P-selectin mAbs. Activating VLA-4 with Mn(2+) on PBBs resulted in
      adhesion to the VCAM-1-transfected CHO cells, indicating that VLA-4 activity on
      PBBs can be regulated, at least in part, through affinity changes. The Mn(2+)
      induced upregulation of basophil VLA-4 affinity was demonstrated directly by
      using a fluorescent ligand for VLA-4 and flow cytometry. CONCLUSIONS: The
      interaction of human CBDBs and PBBs with endothelium under flow conditions is
      mediated in part by both P- and E-selectin. VLA-4 additionally contributes to the
      adhesion of flowing CBDBs. However, the affinity of VLA-4 is too low to support
      the adhesion under flow conditions of unstimulated PBBs.

PMID- 12209097
TI  - High serum thymus and activation-regulated chemokine levels in the lymphocytic
      variant of the hypereosinophilic syndrome.
AB  - The idiopathic hypereosinophilic syndrome is associated with expansion of an IL-5
      producing T-cell subset in a subgroup of patients. Identification of such
      patients is critical to adequate management because there is some evidence that
      they present an increased risk for development of T-cell lymphoma. Although the
      T(H)2-like cells often bear an aberrant surface phenotype and can readily be
      detected with flow cytometry, we now show that lymphocyte phenotyping might be
      normal in some cases. In contrast, serum thymus and activation-regulated
      chemokine levels are consistently increased in such patients compared with others
      with persistent idiopathic hyper-eosinophilia and could therefore represent a
      useful diagnostic tool.

PMID- 12209098
TI  - Suppression of IL-4- and CD40-induced B-lymphocyte activation by intravenous
      immunoglobulin is not mediated through the inhibitory IgG receptor FcgammaRIIb.
AB  - BACKGROUND: Intravenous immunoglobulin (IVIG) has been used extensively in the
      treatment of autoimmune and allergic diseases, but the precise mechanism behind
      its efficacy remains unclear. Ligation of the low-affinity IgG Fc receptor
      FcgammaRIIb can inhibit B-lymphocyte activation. Our laboratory has shown that
      IVIG suppresses proliferation and IgE production by human B cells stimulated with
      IL-4 and anti-CD40 antibodies. OBJECTIVE: We sought to determine whether the
      regulatory action of IVIG is mediated through binding FcgammaRIIb,
      phosphorylation of the receptor, and induction of phosphatases, including SH2
      containing inositol-5'-phosphatase. METHODS: All experiments were performed on
      human tonsillar B cells. Phenotyping was performed by means of flow cytometry.
      Cells were cultured with IL-4 and anti-CD40 antibodies with or without IVIG (10
      mg/mL), and FCgammaRIIb receptor activation and phosphorylation were measured by
      means of Western blot analysis. RESULTS: FcgammaRIIb was the predominant isoform
      of Fcgamma receptor expressed on tonsillar B cells, and preincubation with IVIG
      failed to block binding of FcgammaRIIb antibody. Anti-FcgammaRIIb antibodies did
      not reverse inhibition of B-cell proliferation or IgE production by IVIG.
      Treatment of stimulated B lymphocytes with IVIG for 1 to 60 minutes did not
      change the global protein tyrosine phosphorylation pattern, except for tyrosine
      phosphorylation of an unidentified 30-kd protein. We directly examined tyrosine
      phosphorylation of FcgammaRIIb and its downstream-associated phosphatase, SH2
      containing inositol-5'-phosphatase. Both remained unchanged after IVIG treatment,
      as did other related phosphatases. CONCLUSION: These data argue against the
      involvement of FcgammaRIIb in the inhibition of CD40/IL-4-induced B-cell
      activation by IVIG.

PMID- 12209099
TI  - The leukotriene receptor antagonist montelukast in the treatment of chronic
      idiopathic urticaria: a single-blind, placebo-controlled, crossover clinical
      study.
AB  - BACKGROUND: Chronic idiopathic urticaria (CIU) might be refractory to standard
      therapies. For the patients with severe unremitting CIU who have failed to
      benefit from conventional therapy with antihistamines, other effective and safe
      therapeutic modalities are required. OBJECTIVE: A randomized, single-blind,
      placebo-controlled crossover study was conducted to evaluate the efficacy and
      safety of the new selective leukotriene antagonist montelukast sodium in the
      treatment of refractory CIU. METHODS: Thirty patients with refractory CIU were
      enrolled in the trial. After informed consent was obtained, patients were
      randomly assigned to 2 groups. The patients in group A received 10 mg/d
      montelukast and a nonsedating H(1) antihistamine (cetirizine) when needed for 6
      weeks. After a 2-week washout period, they received placebo for 6 weeks and the
      same H(1) antihistamine as needed. Group B received the treatment vice versa.
      Improvement was monitored by using the self-estimated urticaria activity score,
      which is the sum of the wheal number score and the itch severity score, and the
      antihistamine counts used in each study period. RESULTS: More significant
      decreases occurred in urticaria activity scores with montelukast therapy compared
      with those with placebo therapy (P <.001). H(1) antihistamine use was also
      significantly less frequent during the montelukast period (P <.001). There were
      no significant side effects with montelukast therapy. CONCLUSION: The present
      study results suggest that montelukast might be an effective and safe therapeutic
      agent in the treatment of refractory CIU.

PMID- 12209100
TI  - Active matrix metalloproteinases in the tear fluid of individuals with vernal
      keratoconjunctivitis.
AB  - Corneal epithelial lesions distinguish vernal keratoconjunctivitis (VKC) from
      other ocular allergic diseases. Such lesions result from degradation of the
      corneal epithelial basement membrane, which comprises mostly type IV collagen and
      laminin. Matrix metalloproteinase 2 (MMP-2) and MMP-9 catalyze the degradation of
      these 2 extracellular matrix proteins. The possible role of MMP-2 and MMP-9 in
      the pathogenesis of corneal lesions associated with VKC was investigated by
      assaying tear fluid for the presence of these enzymes. Tear fluid was collected
      from 6 eyes of 6 patients with active VKC, 14 eyes of 14 patients with active
      allergic conjunctivitis, and 6 eyes of 6 nonallergic healthy volunteers. Gelatin
      zymography revealed that the tear fluid of healthy volunteers contained inactive
      proforms of both MMP-2 and MMP-9 but not the active forms of these enzymes.
      Active forms of MMP-2 or MMP-9 were detected in a minority of patients with
      allergic conjunctivitis. However, with the exception of one individual for whom
      active MMP-9 was not detected, tear fluid from all patients with VKC contained
      both proforms and active forms of MMP-2 and MMP-9. These results implicate MMP-2
      and MMP-9 in the pathogenesis of corneal epithelial disorders associated with
      VKC.

PMID- 12209101
TI  - Classification of anti-FcepsilonRI and anti-IgE autoantibodies in chronic
      idiopathic urticaria and correlation with disease severity.
AB  - BACKGROUND: Circulating autoantibodies against FcepsilonRI, IgE, or both occur in
      approximately one third of patients with chronic idiopathic urticaria (CIU), but
      not all autoantibodies initiate histamine release. OBJECTIVE: We sought to
      classify patients with CIU into subsets on the basis of serum bioactivity and
      immunoreactivity and to examine the relationship between newly defined subtype
      and disease severity. METHODS: Sera from patients with CIU (n = 78), dermog
      raphism (n = 15), and cholinergic urticaria (n = 10) and sera from healthy
      subjects (n = 39) were analyzed by means of Western blot analysis for anti
      FcepsilonRI autoantibodies and for histamine release from basophils and dermal
      mast cells. In vivo reactivity of autologous serum was tested by means of
      intradermal injection, and CIU severity was determined on the basis of clinical
      interview. RESULTS: We classified sera from patients with CIU into 5 subsets:
      immunoreactive histamine-releasing anti-FcepsilonRI autoantibodies (n = 20
      [26%]); immunoreactive anti-FcepsilonRI autoantibodies without histamine
      releasing activity (n = 12 [15%]); anti-IgE-like autoantibodies (n = 7 [9%]);
      serum containing a mast cell-specific histamine-releasing factor (n = 7 [9%]);
      and sera with no identifiable factor (n = 32 [41%]). Patients with serum
      histamine-releasing activity had more severe urticaria than patients without such
      activity. Positive skin test responses to autologous sera were associated with
      histamine-releasing anti-FcepsilonRI autoantibodies but not with non-histamine
      releasing anti-FcepsilonRI autoantibodies. Neither healthy subjects nor patients
      with dermographism or cholinergic urticaria had his-tamine-releasing anti
      FcepsilonRI autoantibodies. CONCLUSION: These data support the specificity of
      functional anti-FcepsilonRI autoantibodies to CIU. The identification of
      distinctive subsets of patients suggests that other pathogenic mechanisms occur
      in CIU in addition to direct ligation of FcepsilonRI by autoantibodies causing
      dermal mast cell degranulation. Elucidating these mechanisms might lead to new
      treatments for CIU.

PMID- 12209102
TI  - Effect of mattress encasings on atopic dermatitis outcome measures in a double
      blind, placebo-controlled study: the Dutch mite avoidance study.
AB  - BACKGROUND: House dust mite (HDM) allergen might induce and maintain atopic
      dermatitis (AD). Reduction of allergen load by applying encasings might improve
      the clinical symptoms of AD. OBJECTIVE: We sought to investigate, in a
      randomized, double-blind, placebo-controlled study, whether reducing HDM allergen
      levels by using mattress, duvet, and pillow encasings for 12 months will result
      in improvement in AD symptoms. METHODS: Patients with AD (8-50 years old and
      allergic to HDM), having a Leicester sign score (a dermatitis score) of at least
      1% extent and a severity score of 6 points or greater, were randomly allocated to
      an active (n = 45) or a placebo allergen-avoidance group (n = 41). Avoidance
      measures consisted of applying HDM-impermeable encasings for mattresses, pillows,
      and duvets for the active treatment group and cotton encasings for the placebo
      group. Effect on allergen concentrations (Der p 1 and Der p 1 plus Der f 1),
      Leicester sign score extent and severity, visual analogue scale scores for
      itching and sleeplessness, intradermal test results, atopy patch test results,
      total serum IgE levels, anti-Der p 1-specific IgE levels, and total blood
      eosinophil counts were studied. RESULTS: The active encasings reduced the Der p 1
      allergen concentration in the mattress after 12 months with a factor 2.1 (P
      =.007) and the Der p 1 plus Der f 1 allergen concentration with a factor of 2.5
      (P =.005); no significant change in allergen concentrations in mattresses was
      seen in the placebo group. Although the decrease in allergen load was
      significant, no differences in treatment-induced changes were seen between the
      placebo and active groups. CONCLUSIONS: Use of HDM-impermeable encasings resulted
      in a significant decrease in Der p 1 and Der p 1 plus Der f 1 allergen
      concentrations. However, this reduction in allergen load did not result in
      significant changes in clinical parameters between the groups. Reduction of
      allergens in other environments (work, school, and outdoors) might be equally
      important in improving symptoms of AD.

PMID- 12209104
TI  - Importance of chamber size for the outcome of atopy patch testing in children
      with atopic dermatitis and food allergy.
AB  - Because the small backs of young children offer little space for atopy patch
      testing, it would be helpful to use smaller chambers. We therefore compared 6-mm
      chambers with the 12-mm chambers used in previous studies. We performed 55 double
      blind, placebo-controlled food challenges in 30 children (17 boys, 13 girls) aged
      3 to 58 months (median, 13 months). Sensitivity, specificity, positive predictive
      value, negative predictive value, and efficiency results show that the 12-mm
      chamber size yields much better results than the 6-mm chamber size. Therefore, 12
      mm cups should be used for atopy patch tests with food, even in infants and small
      children.

PMID- 12209103
TI  - HLA-DQ8 and the HLA-DQ8-DR4 haplotype are positively associated with the hevein
      specific IgE immune response in health care workers with latex allergy.
AB  - BACKGROUND: Hevein is one of the most important latex allergens affecting health
      care workers (HCWs). OBJECTIVE: Because the genetically determined susceptibility
      is one important factor regulating type I allergy, the association between the
      hevein-specific IgE immune response and HLA class II alleles of DQB1 and DRB1,
      DRB3, DRB4, and DRB5 was studied. METHODS: The distribution of HLA-DQB1 and DRB1,
      DRB3, DRB4, and DRB5 in 269 HCWs with latex allergy, 56 latex-sensitized patients
      with spina bifida (SB), and 90 nonatopic control subjects under special
      consideration for hevein-specific IgE was examined. RESULTS: Seventy percent
      (189/269) of the HCWs with latex allergy and 39% (22/56) of the latex-sensitized
      patients with SB had increased hevein-specific IgE antibody concentrations (>0.35
      kU/L). HLA data analysis revealed significantly increased phenotype frequencies
      for DQB1*0302 (DQ8; 91/189 [48%]) and DRB1*04 (DR4; 102/189 [54%]) in hevein
      positive HCWs with latex allergy compared with the 80 hevein-negative HCWs with
      latex allergy (DQB1*0302: 16/80 [20%], corrected P value [P (c)] = 7.1 x 10(-4);
      DRB1*04: 23/80 [29%], P (c) =.01) and with control subjects (DQB1*0302: 16/89
      [18%], P (c) = 1 x 10(-4); DRB1*04: 22/90 [24%], P (c) = 3.2 x 10(-4)). The DQ8
      DR4 haplotype frequency was significantly elevated in HCWs with hevein-specific
      IgE antibodies when compared with that in HCWs without hevein-specific IgE
      antibodies (47% vs 18%, P (c) = 5.3 x 10(-4)) or control subjects (47% vs 18%, P
      (c) = 9.6 x 10(-4)). In contrast, latex-sensitized patients with SB with hevein
      specific IgE antibodies showed an increased but not significant DQB1*0302
      frequency (7/22 [32%] vs 2/34 [6%], P =.02, P (c) = not significant) compared
      with that seen in those without hevein-specific IgE antibodies. CONCLUSION: The
      DQB1*0302 (DQ8) alone, the DQB1*0302 (DQ8)-DRB1*04 (DR4) haplotype, or both are
      significantly involved in the hevein-specific IgE immune response in HCWs with
      latex allergy.

PMID- 12209105
TI  - Identification of an 11S globulin as a major hazelnut food allergen in hazelnut
      induced systemic reactions.
AB  - BACKGROUND: Hazelnuts are a common cause of food allergy. Allergic reactions to
      hazelnuts range from oral allergy syndrome caused by cross-reactivity between
      tree pollen and hazelnut proteins to severe anaphylactic reactions. Little
      information is available regarding the identification of pollen-independent
      hazelnut allergens. OBJECTIVE: The aim of the study was to identify these pollen
      independent allergens in patients with hazelnut allergy with systemic reactions.
      METHODS: Extracted hazelnut proteins were separated by means of 2-dimensional
      PAGE, and immunolabeling was performed with individual sera from 14 patients with
      hazelnut-induced systemic reactions. Edman sequencing was performed on a 40-kd
      protein identified as an allergen. In parallel, RNA isolated from hazelnuts was
      used to construct a cDNA library. By using the peptide sequence data,
      oligonucleotide primers were synthesized and used to screen the library. Full
      length cDNA clones were isolated, sequenced, expressed, and screened with patient
      sera. RESULTS: By using 2-dimensional proteomics, a protein fraction at 40 kd was
      recognized by serum IgE from 86% (12/14) of the patients with hazelnut allergy
      with systemic reactions. Two internal amino acid sequences were determined by
      means of Edman sequencing. Screening of the prepared hazelnut cDNA library with
      oligonucleotides based on these internal peptide sequences resulted in isolation
      of a novel protein cDNA. The new protein, named Cor a 9, belongs to the 11S
      globulin seed storage protein family. This family comprises known food allergens
      in peanut (Ara h 3) and soybean (glycine max). The pairwise homology among these
      3 proteins ranges from 45% to 50%. Interestingly, one known IgE-binding epitope
      of Ara h 3 shares 67% of homologous amino acid residues with the corresponding
      area of Cor a 9. The amino acids that differ were previously shown not to be
      critical for IgE binding in Ara h 3. CONCLUSION: Cor a 9 is the first tree pollen
      unrelated hazelnut allergen isolated, sequenced, and cloned. The identification
      of food allergens is the first step toward generating recombinant allergens for
      use in future immunotherapeutic approaches. In addition, the detection of
      conserved IgE epitopes in common food allergens, such as seed storage proteins,
      might be a useful tool for predicting cross-reactivity to certain foods.

PMID- 12209106
TI  - Allergy to cooked white potatoes in infants and young children: A cause of
      severe, chronic allergic disease.
AB  - BACKGROUND: Cases of allergy to cooked potato in children have been reported,
      some with immediate and others with late reactions. The clinical effects of
      chronic allergic reactions to potato and the effectiveness of diet on such
      reactions have not been described previously. OBJECTIVE: We sought to evaluate
      the importance of cooked potato as an allergenic food in individual cases of
      atopy in children. METHODS: Eight atopic children were selected on the basis of
      suspicion of allergy to cooked potatoes: all had potato-specific IgE, 2 of 8 had
      experienced immediate allergic reactions, and 6 of 8 had eczema that improved
      with a potato-elimination diet (decrease in severity scoring of atopic dermatis
      [SCORAD] index of >50%). The patients were evaluated by using skin prick tests
      with homemade cooked and noncooked potato extracts and with a commercial extract
      and by using IgE immunoblots from SDS-PAGE patterns of potato extract. Seven
      patients were challenged with cooked potato. The control group consisted of 9 age
      matched atopic children, 8 of them with eczema. RESULTS: The mean SCORAD index
      decreased from 43.3 before to 11.5 after elimination of potato from the diet.
      Potato CAP values ranged from 3.71 to greater than 100 kUa/L. Potato challenge
      results were positive in 7 of 7 patients. Skin prick test responses were positive
      for cooked potato extracts in 7 of 7 patients, for noncooked extracts in 7 of 7
      patients, and for the commercial extract in 8 of 8 patients compared with in 0 of
      9, 1 of 9, and 1 of 9 subjects in the control group, respectively. During
      immunoblotting, 8 of 8 patient sera recognized one or more protein bands compared
      with 0 of 9 control subject sera. CONCLUSION: Allergy to cooked potatoes is a
      cause of severe allergic disease, with immediate reactions and eczema in some
      atopic infants and young children.

PMID- 12209107
TI  - An allergic reaction to erythropoietin secondary to polysorbate hypersensitivity.

PMID- 12209108
TI  - Multiple intolerance to food additives.

PMID- 12209109
TI  - Hypersensitivity pneumonia: UIP/IPF histopathologic presentation.

PMID- 12209110
TI  - Oral allergy syndrome to sapodilla (Achras zapota).

PMID- 12209111
TI  - Anaphylaxis to latex after ingestion of a cream-filled doughnut contaminated with
      latex.

PMID- 12209112
TI  - Churg-Strauss syndrome is a form of serum sickness.

PMID- 12209113
TI  - Exercise-induced asthma and plasma adenosine: Is there a causative link?

PMID- 12209114
TI  - ACE-inhibitors and angioedema.

PMID- 12209115
TI  - TH1/TH2 immune response.

PMID- 12209117
TI  - The cognitive neuroscience of sleep: neuronal systems, consciousness and
      learning.
AB  - Sleep can be addressed across the entire hierarchy of biological organization. We
      discuss neuronal-network and regional forebrain activity during sleep, and its
      consequences for consciousness and cognition. Complex interactions in
      thalamocortical circuits maintain the electroencephalographic oscillations of non
      rapid eye movement (NREM) sleep. Functional neuroimaging affords views of the
      human brain in both NREM and REM sleep, and has informed new concepts of the
      neural basis of dreaming during REM sleep -- a state that is characterized by
      illogic, hallucinosis and emotionality compared with waking. Replay of waking
      neuronal activity during sleep in the rodent hippocampus and in functional images
      of human brains indicates possible roles for sleep in neuroplasticity. Different
      forms and stages of learning and memory might benefit from different stages of
      sleep and be subserved by different forebrain regions.

PMID- 12209118
TI  - Breaking the neuronal sphere: regulation of the actin cytoskeleton in
      neuritogenesis.
AB  - The sprouting of neurites, which will later become axons and dendrites, is an
      important event in early neuronal differentiation. Studies in living neurons
      indicate that neuritogenesis begins immediately after neuronal commitment, with
      the activation of membrane receptors by extracellular cues. These receptors
      activate intracellular cascades that trigger changes in the actin cytoskeleton,
      which promote the initial breakdown of symmetry. Then, through the regulation of
      gene transcription, and of microtubule and membrane dynamics, the newly formed
      neurite becomes stabilized. A key challenge is to define the molecular machinery
      that regulates the actin cytoskeleton during initial neurite sprouting. We
      propose that analysing the molecules involved in actin-dependent mechanisms in
      non-neuronal systems, such as budding yeast and migrating fibroblasts, could help
      to uncover the secrets of neuritogenesis.

PMID- 12209119
TI  - Why does remyelination fail in multiple sclerosis?
AB  - Multiple sclerosis is a common cause of neurological disability in young adults.
      The disease is complex -- its aetiology is multifactorial and largely unknown;
      its pathology is heterogeneous; and, clinically, it is difficult to diagnose,
      manage and treat. However, perhaps its most frustrating aspect is the inadequacy
      of the healing response of remyelination. This regenerative process generally
      occurs with great efficiency in experimental models, and sometimes proceeds to
      completion in multiple sclerosis. But as the disease progresses, the numbers of
      lesions in which demyelination persists increases, significantly contributing to
      clinical deterioration. Understanding why remyelination fails is crucial for
      devising effective methods by which to enhance it.

PMID- 12209120
TI  - Is there more to GABA than synaptic inhibition?
AB  - In the mature brain, GABA (gamma-aminobutyric acid) functions primarily as an
      inhibitory neurotransmitter. But it can also act as a trophic factor during
      nervous system development to influence events such as proliferation, migration,
      differentiation, synapse maturation and cell death. GABA mediates these processes
      by the activation of traditional ionotropic and metabotropic receptors, and
      probably by both synaptic and non-synaptic mechanisms. However, the functional
      properties of GABA receptor signalling in the immature brain are significantly
      different from, and in some ways opposite to, those found in the adult brain. The
      unique features of the early-appearing GABA signalling systems might help to
      explain how GABA acts as a developmental signal.

PMID- 12209121
TI  - Excitatory actions of gaba during development: the nature of the nurture.
AB  - In the immature brain, GABA (gamma-aminobutyric acid) is excitatory, and GABA
      releasing synapses are formed before glutamatergic contacts in a wide range of
      species and structures. GABA becomes inhibitory by the delayed expression of a
      chloride exporter, leading to a negative shift in the reversal potential for
      choride ions. I propose that this mechanism provides a solution to the problem of
      how to excite developing neurons to promote growth and synapse formation while
      avoiding the potentially toxic effects of a mismatch between GABA-mediated
      inhibition and glutamatergic excitation. As key elements of this cascade are
      activity dependent, the formation of inhibition adds an element of nurture to the
      construction of cortical networks.

PMID- 12209122
TI  - A computational perspective on the neural basis of multisensory spatial
      representations.
AB  - We argue that current theories of multisensory representations are inconsistent
      with the existence of a large proportion of multimodal neurons with gain fields
      and partially shifting receptive fields. Moreover, these theories do not fully
      resolve the recoding and statistical issues involved in multisensory integration.
      An alternative theory, which we have recently developed and review here, has
      important implications for the idea of 'frame of reference' in neural spatial
      representations. This theory is based on a neural architecture that combines
      basis functions and attractor dynamics. Basis function units are used to solve
      the recoding problem, whereas attractor dynamics are used for optimal statistical
      inferences. This architecture accounts for gain fields and partially shifting
      receptive fields, which emerge naturally as a result of the network connectivity
      and dynamics.

PMID- 12209123
TI  - Beyond the role of glutamate as a neurotransmitter.
AB  - Glutamate is the principal excitatory neurotransmitter of the central nervous
      system, but many studies have expanded its functional repertoire by showing that
      glutamate receptors are present in a variety of non-excitable cells. How does
      glutamate receptor activation modulate their activity? Do non-excitable cells
      release glutamate, and, if so, how? These questions remain enigmatic. Here, we
      review the current knowledge on glutamatergic signalling in non-neuronal cells,
      with a special emphasis on astrocytes.

PMID- 12209124
TI  - Seven-transmembrane receptors.
AB  - Seven-transmembrane receptors, which constitute the largest, most ubiquitous and
      most versatile family of membrane receptors, are also the most common target of
      therapeutic drugs. Recent findings indicate that the classical models of G
      protein coupling and activation of second-messenger-generating enzymes do not
      fully explain their remarkably diverse biological actions.

PMID- 12209125
TI  - Stats: transcriptional control and biological impact.
AB  - Extracellular proteins bound to cell-surface receptors can change nuclear gene
      expression patterns in minutes, with far-reaching consequences for development,
      cell growth and homeostasis. The signal transducer and activator of transcription
      (STAT) proteins are among the most well studied of the latent cytoplasmic signal
      dependent transcription-factor pathways. In addition to several roles in normal
      cell decisions, dysregulation of STAT function contributes to human disease,
      making the study of these proteins an important topic of current research.

PMID- 12209126
TI  - Mixed-lineage kinase control of JNK and p38 MAPK pathways.
AB  - Mixed-lineage kinases (MLKs) are serine/threonine protein kinases that regulate
      signalling by the c-Jun amino-terminal kinase (JNK) and p38 mitogen-activated
      protein kinase (MAPK) pathways. MLKs are represented in the genomes of both
      Caenorhabditis elegans and Drosophila melanogaster. The Drosophila MLK Slipper
      regulates JNK to control dorsal closure during embryonic morphogenesis. In
      mammalian cells, MLKs are implicated in the control of apoptosis and are
      potential drug targets for many neurodegenerative diseases.

PMID- 12209127
TI  - Gamma-secretase-mediated proteolysis in cell-surface-receptor signalling.
AB  - Many cell-surface receptors transmit signals to the nucleus through complex
      protein cascades. By contrast, the Notch signalling pathway uses a relatively
      direct mechanism, in which the intracellular domain of the receptor is liberated
      by intramembrane cleavage and translocates to the nucleus. This critical cleavage
      is mediated by the gamma-secretase complex, and new findings reveal that this
      mechanism is used by various receptors, although many questions remain about the
      biochemical details.

PMID- 12209128
TI  - Listening in on bacteria: acyl-homoserine lactone signalling.
AB  - Bacterial cell-to-cell signalling has emerged as a new area in microbiology.
      Individual bacterial cells communicate with each other and co-ordinate group
      activities. Although a lot of detail is known about the mechanisms of a few well
      characterized bacterial communication systems, other systems have been discovered
      only recently. Bacterial intercellular communication has become a target for the
      development of new anti-virulence drugs.

PMID- 12209129
TI  - Signalling shortcuts: cell-surface receptors in the nucleus?
AB  - Do cell-surface growth-factor receptors and their ligands accumulate in the
      nucleoplasm under physiological conditions? And, if so, how do they get there and
      what function do they serve in this location? Recent advances have provided
      tantalizing hints to the answers to these questions, and hold the key to
      identifying a new mode of signal transduction.

PMID- 12209130
TI  - Signalling through nuclear receptors.
AB  - A century ago, secretions from the pancreas were described as 'hormones', which
      we now know are secreted from all ductless glands. The development of various
      technologies has already contributed a great deal -- and will undoubtedly offer
      more -- to our understanding of their mode of action.

PMID- 12209131
TI  - Cyclic nucleotide research -- still expanding after half a century.
AB  - Since the discovery in 1957 that cyclic AMP acts as a second messenger for the
      hormone adrenaline, interest in this molecule and its companion, cyclic GMP, has
      grown. Over a period of nearly 50 years, research into second messengers has
      provided a framework for understanding transmembrane signal transduction,
      receptor-effector coupling, protein-kinase cascades and downregulation of drug
      responsiveness. The breadth and impact of this work is reflected by five
      different Nobel prizes.

PMID- 12209132
TI  - WASp in immune-system organization and function.
AB  - The regulation of many immunological events depends on systems that mediate
      dynamic actin reorganization in response to signals from the cell membrane. The
      Wiskott-Aldrich syndrome protein (WASp) is the founding member of a family of
      proteins that have emerged as crucial effectors of Rho GTPases and activators of
      the cytoskeletal-organizing complex Arp2/3. Now, WASp has been shown to be
      intimately involved in many pathways that influence the function of the immune
      system. Disturbances in these systems result in the complex immunodysregulation
      of Wiskott-Aldrich syndrome.

PMID- 12209133
TI  - Coeliac disease: dissecting a complex inflammatory disorder.
AB  - The disease mechanisms of complex inflammatory disorders are difficult to define
      because of extensive interactions between genetic and environmental factors.
      Coeliac disease is a typical complex inflammatory disorder, but this disease is
      unusual in that crucial genetic and environmental factors have been identified.
      This knowledge has allowed functional studies of the predisposing HLA molecules,
      the identification of antigenic epitopes and detailed studies of disease-relevant
      T cells in coeliac disease. This dissection of the pathogenic mechanisms of
      coeliac disease has uncovered principles that are relevant to other chronic
      inflammatory diseases.

PMID- 12209134
TI  - Natural killer cells and pregnancy.
AB  - The fetus is considered to be an allograft that, paradoxically, survives
      pregnancy despite the laws of classical transplantation immunology. There is no
      direct contact of the mother with the embryo, only with the extraembryonic
      placenta as it implants in the uterus. No convincing evidence of uterine maternal
      T-cell recognition of placental trophoblast cells has been found, but instead,
      there might be maternal allorecognition mediated by uterine natural killer cells
      that recognize unusual fetal trophoblast MHC ligands.

PMID- 12209136
TI  - Viruses and interferon: a fight for supremacy.
AB  - The action of interferons (IFNs) on virus-infected cells and surrounding tissues
      elicits an antiviral state that is characterized by the expression and antiviral
      activity of IFN-stimulated genes. In turn, viruses encode mechanisms to
      counteract the host response and support efficient viral replication, thereby
      minimizing the therapeutic antiviral power of IFNs. In this review, we discuss
      the interplay between the IFN system and four medically important and challenging
      viruses -- influenza, hepatitis C, herpes simplex and vaccinia -- to highlight
      the diversity of viral strategies. Understanding the complex network of cellular
      antiviral processes and virus-host interactions should aid in identifying new and
      common targets for the therapeutic intervention of virus infection. This effort
      must take advantage of the recent developments in functional genomics,
      bioinformatics and other emerging technologies.

PMID- 12209137
TI  - Comparative analyses of immunoglobulin genes: surprises and portents.
AB  - The study of immunoglobulin genes in non-mouse and non-human models has shown
      that different vertebrate groups have evolved distinct methods of generating
      antibody diversity. By contrast, the development of T cells in the thymus is
      quite similar in all of the species that have been examined. The three mechanisms
      by which B cells uniquely modify their immunoglobulin genes -- somatic
      hypermutation, gene conversion and class switching -- are increasingly believed
      to share some fundamental mechanisms, which studies in different vertebrate
      groups have helped (and will continue to help) to resolve. When these mechanisms
      are better understood, we should be able to look to the constitutive pathways
      from which they have evolved and perhaps determine whether the rearrangement of
      variable, diversity and joining antibody gene segments -- V(D)J recombination --
      was superimposed on an existing adaptive immune system.

PMID- 12209135
TI  - Nf-kappa B, chemokine gene transcription and tumour growth.
AB  - The constitutive expression of angiogenic and tumorigenic chemokines by tumour
      cells facilitates the growth of tumours. The transcription of these angiogenic
      and tumorigenic chemokine genes is modulated, in part, by the nuclear factor
      kappa B (NF-kappa B) family of transcription factors. In some tumours, there is
      constitutive activation of the kinases that modulate the activity of inhibitor of
      NF-kappa B (I kappa B) kinase (IKK), which leads to the constitutive activation
      of members of the NF-kappa B family. This activation of NF-kappa B is associated
      with the dysregulation of transcription of genes that encode cytokines,
      chemokines, adhesion factors and inhibitors of apoptosis. In this review, I
      discuss the factors that lie upstream of the NF-kappa B cascade that are
      activated during tumorigenesis and the role of the putative NF-kappa B
      enhanceosome in constitutive chemokine gene transcription during tumorigenesis.

PMID- 12209138
TI  - Telomeres in T and B cells.
AB  - Telomeres are the structures at the ends of linear chromosomes. In mammalian
      cells, they consist of hexanucleotide (TTAGGG) repeats, together with many
      associated proteins. In the absence of a compensatory mechanism, dividing cells
      undergo gradual telomere erosion until a critical degree of shortening results in
      chromosomal abnormalities and cell death or senescence. For T and B cells, the
      ability to undergo extensive cell division and clonal expansion is crucial for
      effective immune function. This article describes our current understanding of
      telomere-length regulation in lymphocytes and its implications for immune
      function.

PMID- 12209139
TI  - Antibodies, viruses and vaccines.
AB  - Neutralizing antibodies are crucial for vaccine-mediated protection against viral
      diseases. They probably act, in most cases, by blunting the infection, which is
      then resolved by cellular immunity. The protective effects of neutralizing
      antibodies can be achieved not only by neutralization of free virus particles,
      but also by several activities directed against infected cells. In certain
      instances, non-neutralizing antibodies contribute to protection. Several viruses,
      such as HIV, have evolved mechanisms to evade neutralizing-antibody responses,
      and these viruses present special challenges for vaccine design that are now
      being tackled.

PMID- 12209140
TI  - Treasures and traps in genome-wide data sets: case examples from yeast.
AB  - Since the publication of the Saccharomyces cerevisiae genome sequence, much
      effort has been dedicated to developing high-throughput techniques to generate
      comprehensive information about the function and dynamics of all genes in this
      yeast's genome. These techniques have generated data sets that typically contain
      large amounts of reliable and valuable biological information. Nevertheless,
      there are also uncertainties that are associated with such large-scale studies,
      which we discuss in this review. These uncertainties increase with the complexity
      of the organism under study. On the basis of the results from yeast, we should
      learn much from human and mouse genomic data sets. However, as with yeast data
      sets, they might also contain misleading results.

PMID- 12209141
TI  - Chromatin modification and epigenetic reprogramming in mammalian development.
AB  - The developmental programme of embryogenesis is controlled by both genetic and
      epigenetic mechanisms. An emerging theme from recent studies is that the
      regulation of higher-order chromatin structures by DNA methylation and histone
      modification is crucial for genome reprogramming during early embryogenesis and
      gametogenesis, and for tissue-specific gene expression and global gene silencing.
      Disruptions to chromatin modification can lead to the dysregulation of
      developmental processes, such as X-chromosome inactivation and genomic
      imprinting, and to various diseases. Understanding the process of epigenetic
      reprogramming in development is important for studies of cloning and the clinical
      application of stem-cell therapy.

PMID- 12209142
TI  - Arteries and veins: making a difference with zebrafish.
AB  - Arteries and veins are structurally different and have long been functionally
      defined by the direction of blood flow that they carry. However, a growing body
      of evidence indicates that the identity of the endothelial cells that line these
      vessels is determined in the developing embryo, before circulation begins. Recent
      work on the zebrafish has led to the identification of signals that are
      responsible for arterial and venous differentiation of endothelial cells, and
      highlights the unique benefits of this model organism in the study of vascular
      development.

PMID- 12209143
TI  - The art and design of genetic screens: filamentous fungi.
AB  - In the 1940s, screens for metabolic mutants of the filamentous fungus Neurospora
      crassa established the fundamental, one-to-one relationship between a gene and a
      specific protein, and also established fungi as important genetic organisms.
      Today, a wide range of filamentous species, which represents a billion years of
      evolutionary divergence, is used for experimental studies. The developmental
      complexity of these fungi sets them apart from unicellular yeasts, and allows the
      development of new screens that enable us to address biological questions that
      are relevant to all eukaryotes.

PMID- 12209144
TI  - Computational prediction of eukaryotic protein-coding genes.
AB  - The human genome sequence is the book of our life. Buried in this large volume
      are our genes, which are scattered as small DNA fragments throughout the genome
      and comprise a small percentage of the total text. Finding these indistinct
      'needles' in a vast genomic 'haystack' can be extremely challenging. In response
      to this challenge, computational prediction approaches have proliferated in
      recent years that predict the location and structure of genes. Here, I discuss
      these approaches and explain why they have become essential for the analyses of
      newly sequenced genomes.

PMID- 12209145
TI  - Taking stock of our models: the function and future of stock centres.
AB  - Stock centres for our animal models are as important as other scientific
      resources, such as the primary literature or genome databases. But they need
      forward planning, international cooperation and secure funding to keep pace with
      the explosion in functional genomics that relies so heavily on them.

PMID- 12209146
TI  - Headwaters of the zebrafish -- emergence of a new model vertebrate.
AB  - The understanding of vertebrate development has advanced considerably in recent
      years, primarily due to the study of a few model organisms. The zebrafish, the
      newest of these models, has risen to prominence because both genetic and
      experimental embryological methods can be easily applied to this animal. The
      combination of approaches has proven powerful, yielding insights into the
      formation and function of individual tissues, organ systems and neural networks,
      and into human disease mechanisms. Here, we provide a personal perspective on the
      history of zebrafish research, from the assembly of the first genetic and
      embryological tools through to sequencing of the genome.

PMID- 12209147
TI  - ATPases as drug targets: learning from their structure.
AB  - ATPases are involved in several cellular functions, and are at the origin of
      various human diseases. They are therefore attractive drug targets, and various
      ATPase inhibitors are already on the market. However, most of these drugs are
      active without binding directly to the nucleotide-binding site. An alternative
      strategy to inhibit ATPases is to design competitive ATP inhibitors. This
      approach, which has been used successfully to design protein-kinase inhibitors,
      depends on the structure of the nucleotide-binding site. This review describes
      the structural features of the nucleotide-binding site of various ATPases and
      analyses how this structural information can be exploited for drug discovery.

PMID- 12209148
TI  - Phosphodiesterase 5 inhibitors: current status and potential applications.
AB  - Phosphodiesterase enzymes convert cyclic GMP and cyclic AMP to the corresponding
      nucleotide monophosphates. Phosphodiesterase 5 (PDE5) inhibition is now a widely
      accepted and efficacious therapeutic option for the treatment of erectile
      dysfunction in men, as a result of extensive clinical experience with sildenafil
      and other new PDE5 inhibitors. Research in the field continues at a substantial
      level to identify new, selective PDE5 inhibitors and to investigate their
      usefulness and activity in other areas. This review summarizes recent clinical
      trials with PDE5 inhibitors, advances in medicinal chemistry, and other
      activities and potential applications of this class of compounds.

PMID- 12209150
TI  - Protein tyrosine phosphatase 1B inhibitors for diabetes.
AB  - Increased incidence of type 2 diabetes mellitus and obesity has elevated the
      medical need for new agents to treat these disease states. Resistance to the
      hormones insulin and leptin are hallmarks of both type 2 diabetes and obesity.
      Drugs that can ameliorate this resistance should be effective in treating type 2
      diabetes and possibly obesity. Protein tyrosine phosphatase 1B (PTP1B) is thought
      to function as a negative regulator of insulin and leptin signal transduction.
      This article reviews PTP1B as a novel target for type 2 diabetes, and looks at
      the challenges in developing small-molecule inhibitors of this phosphatase.

PMID- 12209149
TI  - Clinical proteomics: translating benchside promise into bedside reality.
AB  - The ultimate goal of proteomics is to characterize the information flow through
      protein networks. This information can be a cause, or a consequence, of disease
      processes. Clinical proteomics is an exciting new subdiscipline of proteomics
      that involves the application of proteomic technologies at the bedside, and
      cancer, in particular, is a model disease for studying such applications. Here,
      we describe proteomic technologies that are being developed to detect cancer
      earlier, to discover the next generation of targets and imaging biomarkers, and
      finally to tailor the therapy to the patient.

PMID- 12209151
TI  - Pharmacotherapy of addictions.
AB  - Addiction to drugs, such as heroin, cocaine and alcohol, exacts great human and
      financial costs on society, but the development of pharmacotherapies for
      addiction has been largely neglected by the pharmaceutical industry. With
      advances in our understanding of the underlying biology of addictions now opening
      the door for the development of novel pharmacotherapies, it could be time for a
      reassessment of involvement in this increasingly important therapeutic area.
      Here, we summarize the current approved and implemented pharmacotherapeutic
      approaches to the treatment of addiction, and then highlight the most promising
      areas for future drug development from the perspective of our laboratory and our
      National Institutes of Health (NIH) National Institute on Drug Abuse (NIDA)
      Research Center.

PMID- 12209152
TI  - The druggable genome.
AB  - An assessment of the number of molecular targets that represent an opportunity
      for therapeutic intervention is crucial to the development of post-genomic
      research strategies within the pharmaceutical industry. Now that we know the size
      of the human genome, it is interesting to consider just how many molecular
      targets this opportunity represents. We start from the position that we
      understand the properties that are required for a good drug, and therefore must
      be able to understand what makes a good drug target.

PMID- 12209153
TI  - Drug addictions: towards socially accepted and medically treatable diseases.
AB  - What is the disease that affects more than 30 million individuals in the United
      States and Europe, is a leading cause of death and costs 2-3.5% of gross domestic
      product? The answer -- alcohol abuse and drug addictions -- still surprises many,
      and in general, addictions are undertreated. But advances in the understanding of
      the underlying biology and clinical manifestations of addictions are creating new
      opportunities for the development of novel pharmacotherapies to complement
      psychosocial interventions.

PMID- 12209154
TI  - The Bcl2 family: regulators of the cellular life-or-death switch.
AB  - Tissue homeostasis is regulated by apoptosis, the cell-suicide programme that is
      executed by proteases called caspases. The Bcl2 family of intracellular proteins
      is the central regulator of caspase activation, and its opposing factions of anti
      and pro-apoptotic members arbitrate the life-or-death decision. Apoptosis is
      often impaired in cancer and can limit conventional therapy. A better
      understanding of how the Bcl2 family controls caspase activation should result in
      new, more effective therapeutic approaches.

PMID- 12209155
TI  - Strategies for MMP inhibition in cancer: innovations for the post-trial era.
AB  - For more than two decades, the view that tumour-associated matrix
      metalloproteinases (MMPs) were required for peritumour tissue degradation and
      metastasis dominated the drive to develop MMP inhibitors as anticancer
      therapeutics. Until recently, clinical trials with MMP inhibitors have yielded
      disappointing results, highlighting the need for better insight into the
      mechanisms by which this growing family of multifunctional enzymes contribute to
      tumour growth. It is now recognized that MMP activity is tightly regulated at
      several levels, providing new avenues for blocking these enzymes. What are the
      different approaches that can be used to target MMPs, and which of these might
      lead to new therapeutic strategies for cancer?

PMID- 12209156
TI  - Molecular basis of the VHL hereditary cancer syndrome.
AB  - The von Hippel-Lindau hereditary cancer syndrome was first described about 100
      years ago. The unusual clinical features of this disorder predicted a role for
      the von Hippel-Lindau gene (VHL) in the oxygen-sensing pathway. Indeed, recent
      studies of this gene have helped to decipher how cells sense changes in oxygen
      availability, and have revealed a previously unappreciated role of prolyl
      hydroxylation in intracellular signalling. These studies, in turn, are laying the
      foundation for the treatment of a diverse set of disorders, including cancer,
      myocardial infarction and stroke.

PMID- 12209157
TI  - Molecular imaging of cancer with positron emission tomography.
AB  - The imaging of specific molecular targets that are associated with cancer should
      allow earlier diagnosis and better management of oncology patients. Positron
      emission tomography (PET) is a highly sensitive non-invasive technology that is
      ideally suited for pre-clinical and clinical imaging of cancer biology, in
      contrast to anatomical approaches. By using radiolabelled tracers, which are
      injected in non-pharmacological doses, three-dimensional images can be
      reconstructed by a computer to show the concentration and location(s) of the
      tracer of interest. PET should become increasingly important in cancer imaging in
      the next decade.

PMID- 12209158
TI  - Are vitamin and mineral deficiencies a major cancer risk?
AB  - Diet is estimated to contribute to about one-third of preventable cancers --
      about the same amount as smoking. Inadequate intake of essential vitamins and
      minerals might explain the epidemiological findings that people who eat only
      small amounts of fruits and vegetables have an increased risk of developing
      cancer. Recent experimental evidence indicates that vitamin and mineral
      deficiencies can lead to DNA damage. Optimizing vitamin and mineral intake by
      encouraging dietary change, multivitamin and mineral supplements, and fortifying
      foods might therefore prevent cancer and other chronic diseases.

PMID- 12209159
TI  - How acute promyelocytic leukaemia revived arsenic.
AB  - Despite its many therapeutic qualities, arsenic trioxide has been more commonly
      remembered as Madame Bovary's poison than as an anticancer drug. The ability of
      arsenic trioxide to treat acute promyelocytic leukaemia has radically changed
      this view, providing new insights into the pathogenesis of this malignancy and
      raising hopes that arsenicals might be useful in treating other cancers.

PMID- 12209160
TI  - NTP technical report on the toxicity studies of D&C Yellow No. 11 in F344/N Rats
      and B6C3F1 Mice (Feed Studies) (CAS No. 8003-22-3).
AB  - Toxicity studies were conducted by administering D&C Yellow No. 11 (approximately
      99%percnt; pure) in feed at dietary concentrations of up to 50,000 ppm to groups
      of F344/N rats and B6C3F1 mice of each sex for 14 days or 13 weeks. A separate
      study was conducted to determine the effects of feeding diets containing D&C
      Yellow No. 11 to female rats during a reproductive cycle and to their offspring.
      Although the estimated intake of D&C Yellow No. 11 by mice was more than twice
      that by rats, the results of the 14-day and 13- week studies were similar for
      both rats and mice. In both species, D&C Yellow No. 11 caused no deaths (5
      animals per group in the 14- day studies and 10 per group in the 13-week studies)
      but did reduce body weight gain slightly in rats of each sex exposed to 17,000 or
      50,000 ppm. Liver weights were increased in dosed rats and mice. There was
      minimal-to-mild degeneration of the periportal portion of the liver lobules of
      rats at dietary concentrations of 1,700 ppm and higher and of mice at 5,000 ppm
      and higher. A dose- related yellow-brown pigment was observed in hepatocytes,
      Kupffer cells, and biliary epithelium of the liver of each sex and species and in
      the tubular epithelium of the kidney of rats of each sex. Hepatocellular
      degeneration progressed slightly in severity with increased time of exposure
      (i.e., 14 days to 13 weeks) in rats but not in mice. The number and size of
      hyaline droplets in the tubular epithelium of the cortex and outer medulla of the
      kidney were increased in all dosed groups of male rats. In a perinatal toxicity
      study, body weight gain of rat dams given diets containing as much as 50,000 ppm
      D&C Yellow No. 11 for 4 weeks before mating to unexposed males was similar to
      that of controls at the time of mating but was lower at parturition and weaning.
      However, fertility, gestation length, litter size, and pup birth weights were
      unaffected by exposure. At weaning, body weights of pups from all dosed dams
      (5,000, 17,000, and 50,000 ppm) were lower than weights of pups from the
      controls. After exposure to DC Yellow No. 11 for 4 weeks through the milk and to
      feed containing the same dietary concentrations that the dams received, weights
      of the 5,000-ppm pups were similar to those of the controls, but weights of the
      17,000- and 50,000-ppm dose groups remained depressed. Microscopic evaluation
      showed lesions in the pups in all dosed groups; these lesions were similar to
      those described in the liver and kidney of rats in the 14-day and 13-week
      studies, including the male rat kidney cytoplasmic alterations. The results of
      these studies indicate that compound-related effects occurred at all dietary
      concentrations of DC Yellow No. 11; i.e., liver weights were increased in dosed
      rats and mice, and there was an increase in the number and size of hyaline
      droplets in all dosed groups of male rats. Synonyms: 2-(2-quinolyl)-1,3
      indanedione; Arlosol Yellow S; Chinoline Yellow D soluble in spirits; Chinoline
      ZSS; CI 47000; C.I. Solvent Yellow 33; Nitro Fast Yellow SL; Oil Yellow SIS;
      Petrol Yellow C; Quinolin Yellow A Spirit Soluble; Quinoline Yellow Base;
      Quinoline Yellow Spirit Soluble; Quinoline Yellow SS; Solvent Yellow 33; Waxoline
      Yellow T.

PMID- 12209161
TI  - NTP technical report on the toxicity studies of 1,2,4,5-Tetrachlorobenzene in
      F344/N Rats and B6C3F1 Mice (Feed Studies) (CAS No. 95-94-3).
AB  - Toxicology studies were conducted by exposing groups of F344/N rats and B6C3F1
      mice of each sex to 1,2,4,5-tetrachlorobenzene (greater than 99%percnt; pure) at
      various concentrations in formulated diets for 14 days or 13 weeks. Dietary
      concentrations were 0, 30, 100, 300, 1,000, or 3,000 ppm 1,2,4,5
      tetrachlorobenzene in the 14 day studies. All rats survived to the end of the
      studies, but all mice in the 3,000-ppm groups died (five animals per group).
      Histologically, exposed male rats had an accumulation of abnormal hyaline
      droplets in the renal cortical epithelium. Significant histologic lesions were
      not seen in female rats or in mice of either sex. Dietary concentrations were 0,
      30, 100, 300, 1,000, or 2,000 ppm 1,2,4,5-tetrachlorobenzene in the 13-week
      studies (10 animals per group). All rats survived to the end of the studies; two
      female mice in the 2,000-ppm group were killed in a moribund condition. Body
      weight gains in the higher dose groups of rats and mice were less than those of
      controls. In exposed male rats, lesions included renal cortical tubular
      epithelial hyaline droplet formation, cortical tubular regeneration, and
      medullary granular casts and mineralization. This spectrum of renal lesions in
      male rats is consistent with the entity described as "hydrocarbon or hyaline
      droplet nephropathy." In some exposed female rats (30- to 2,000-ppm groups),
      there was renal cortical tubular cell regeneration plus accumulation of an
      unidentified yellow-brown pigment in the renal cortical epithelium. Centrilobular
      hepatocellular hypertrophy was observed in the livers of exposed male and female
      rats. In mice, minimal-to-mild centrilobular hepatocellular hypertrophy was
      present in males in the 1,000 and 2,000-ppm groups and in females in the 2,000
      ppm group. Minimal-to-mild individual hepatocyte degeneration occurred in mice of
      each sex in the 2,000-ppm groups. Increased serum sorbitol dehydrogenase and
      alanine aminotransferase activity was observed in the two highest dose groups of
      male and female mice and indicated hepatocellular injury. Thyroid follicular cell
      hypertrophy was present in male rats in the 300- to 2,000-ppm groups and in
      female rats in the 100- to 2,000-ppm groups. Decreased free thyroxin and total
      thyroxin concentrations in male rats in the 300- to 2,000 ppm groups and female
      rats in the 30- to 2,000-ppm groups indicated a primary hypothyroid state.
      Hematologic findings for rats that received 1,000 or 2,000 ppm included
      significantly decreased hematocrit values, hemoglobin concentration, and
      erythrocyte counts for males and decreased mean cell volume for females; for
      mice, decreased hemoglobin concentrations, mean corpuscular hemoglobin,
      hematocrit, and mean cell volume were observed in males in the 2,000-ppm group
      and in females in the 1,000- and 2,000-ppm groups. These findings suggest a
      poorly regenerative anemia in both species. The no-observed-effect level (NOEL)
      for histologic lesions was 30 ppm for male and female rats. The NOEL for
      histologic lesions in male and female mice was 300 ppm. Synonyms: s
      tetrachlorobenzene; benzene tetrachloride. (NOTE: These studies were supported in
      part by funds from the Comprehensive Environmental Response, Compensation, and
      Liability Act trust fund (Superfund) by an interagency agreement with the Agency
      for Toxic Substances and Disease Registry, U.S. Public Health Service.)

PMID- 12209162
TI  - NTP technical report on the toxicity studies of Pentachlorobenzene in F344/N Rats
      and B6C3F1 Mice (Feed Studies) (CAS No. 608-93-5).
AB  - Toxicology studies were conducted by exposing groups of F344/N rats and B6C3F1
      mice of each sex to pentachlorobenzene (99%percnt; pure) in feed for 15 days or
      13 weeks. Exposure concentrations were 0, 100, 330, 1,000, 3,300, or 10,000 ppm
      pentachlorobenzene in the 15-day studies (five animals of each sex per group per
      species). All rats that received 10,000 ppm and all mice that received 3,300 or
      10,000 ppm died. Of the exposed rats that survived to the end of the studies,
      males had an accumulation of abnormal hyaline droplets in the renal cortical
      epithelium and males and females had centrilobular hepatocellular hypertrophy.
      Chemical-related lesions were not observed in exposed mice. Exposure
      concentrations were 0, 33, 100, 330, 1,000, or 2,000 ppm pentachlorobenzene in
      the 13-week studies (10 animals of each sex per group per species). No compound
      related deaths occurred. Body weights of exposed rats but not of mice were lower
      than those of controls. In male rats, dose-related histologic lesions included
      renal tubular epithelial hyaline droplet formation and medullary granular casts
      and mineralization. This spectrum of renal lesions in male rats is consistent
      with the entity described as "hydrocarbon or hyaline droplet nephropathy."
      Exacerbation of spontaneous nephropathy characterized by renal tubular cell
      regeneration and homogeneous intratubular protein casts was seen in rats of each
      sex. Urinary protein concentration was increased in male and female rats in the
      1,000- and 2,000-ppm groups; this change was especially prominent in males.
      Urinary glucose concentration was increased in male rats in the 330- to 2,000-ppm
      groups and in female rats in the 1,000 and 2,000-ppm groups. Centrilobular
      hepatocellular hypertrophy was observed in exposed male and female rats.
      Unidentified yellow-brown pigment granules were present in hepatocytes and renal
      tubular epithelium in exposed animals of each sex but were more prominent in
      females. These granules possibly contained porphyrins. The only exposure-related
      histologic lesion in mice of either sex was centrilobular hepatocellular
      hypertrophy. Significant, but not dose-related, increases of liver porphyrin
      concentrations were observed in exposed male rats; female rats in the 2,000-ppm
      group also had increased liver porphyrin concentrations. Liver porphyrin
      concentrations were significantly increased in the 1,000- and 2,000-ppm groups of
      mice of each sex. Increased sorbitol dehydrogenase concentrations in exposed rats
      and mice of each sex were attributed to mild hepatocyte injury. Minimal thyroid
      follicular cell hypertrophy was also present in male and female rats in the 1,000
      and 2,000-ppm groups. Free thyroxin and total thyroxin concentrations were
      significantly decreased in exposed male and female rats; these data indicate
      moderate hypothyroxinemia in exposed animals. Hematologic findings in exposed
      rats included decreased hematocrit, hemoglobin concentration, erythrocyte count
      (males), mean corpuscular hemoglobin, mean erythrocyte volume, and mean
      corpuscular hemoglobin concentration; these findings are consistent with a mild
      to-moderate anemia that is microcytic (decreased mean cell volume), hypochromic
      (decreased mean corpuscular hemoglobin concentration, females), and poorly
      regenerative (slight-to-no change in reticulocyte counts). The no-observed effect
      levels (NOELs) for histologic lesions were 33 ppm for male rats and 330 ppm for
      female rats. The NOEL for histologic lesions in female mice was 100 ppm. An NOEL
      was not reached for male mice. Synonyms: 1,2,3,4,5-Pentachlorobenzene;
      quintochlorobenzene. (NOTE: These studies were supported in part by funds from
      the Comprehensive Environmental Response, Compensation, and Liability Act trust
      fund (Superfund) by an interagency agreement with the Agency for Toxic Substances
      and Disease Registry, U.S. Public Health Service.)

PMID- 12209163
TI  - NTP technical report on the toxicity studies of Cobalt Sulfate Heptahydrate in
      F344/N Rats and B6C3F1 Mice (Inhalation Studies) (CAS No. 10026-24-1).
AB  - Toxicology studies of cobalt sulfate heptahydrate (99%percnt; pure) were
      conducted by exposing groups of F344/N rats and B6C3F1 mice of each sex to a
      cobalt sulfate heptahydrate aerosol 6 hours per day, 5 days per week, for 16 days
      or 13 weeks. In 16-day studies, all rats and mice exposed at the top
      concentration of 200 mg cobalt sulfate/m3 died (5 animals per group); partial
      survival was seen in the 50 mg/m(3) exposure groups. Degeneration of the
      olfactory epithelium and necrotizing inflammation occurred in the nose of all
      rats and mice that died and in animals exposed to 50 mg/m(3). Necrotizing
      inflammation was observed in the larynx and trachea of rats and mice at
      concentrations as low as 5 mg/m(3), and a similar lesion was present in the
      bronchi at exposure concentrations of 50 mg/m(3) or higher. Regenerative and
      inflammatory lesions, including peribronchial and septal fibrosis in the lung,
      were found in rats and mice exposed to 50 mg/m(3). In 13-week studies, all rats,
      all female mice, and all but 2 male mice exposed at the top concentration
      survived to the end of the studies (target exposure concentrations of 0, 0.3, 1,
      3, 10, and 30 mg/m(3), 10 animals per group). Rats and mice exposed to 30 mg/m(3)
      lost weight during the first exposure week and then gained weight at the same
      rate as controls. Lung weights were increased over those of controls in rats
      exposed at concentrations as low as 1 mg/m(3) and in mice exposed to 10 mg/m(3)
      or more. Polycythemia was observed in rats exposed to cobalt sulfate but not in
      mice. Sperm motility was decreased in mice exposed at 3 mg/m(3) or at higher
      concentrations (lower concentrations were not evaluated), and increased numbers
      of abnormal sperm were found in mice exposed to 30 mg/m(3). Testis and epididymal
      weights were decreased in mice exposed to 30 mg/m(3). Cobalt content in the urine
      of rats increased with increasing atmospheric cobalt exposure. Lesions seen in
      the respiratory tract in 13-week studies in rats and mice included degeneration
      of the olfactory epithelium, squamous metaplasia of the respiratory epithelium,
      and inflammation in the nose; inflammation, necrosis, squamous metaplasia, ulcers
      (rats), and inflammatory polyps (rats) of the larynx; squamous metaplasia of the
      trachea (mice); and histiocytic infiltrates, bronchiolar regeneration,
      peribronchiolar and septal fibrosis, and epithelial hyperplasia in the alveoli of
      the lung. The most sensitive tissue was the larynx, with squamous metaplasia
      observed in rats and mice at the lowest exposure concentration of 0.3 mg/m(3).
      Thus, a no-observed-adverse-effect level was not reached in these studies. (NOTE:
      These studies were supported in part by funds from the Comprehensive
      Environmental Response, Compensation, and Liability Act trust fund (Superfund) by
      an interagency agreement with the Agency for Toxic Substances and Disease
      Registry, U.S. Public Health Service.)

PMID- 12209164
TI  - NTP technical report on the toxicity studies of 1,2-Dichloroethane (Ethylene
      Dichloride) in F344/N Rats, Sprague Dawley Rats, Osborne-Mendel Rats, and B6C3F1
      Mice (Drinking Water and Gavage Studies) (CAS No. 107-06-2).
AB  - Thirteen-week studies were conducted to investigate potential differences in rat
      strain susceptibility to 1,2-dichloroethane toxicity. F344/N rats, Sprague Dawley
      rats, Osborne-Mendel rats, and B6C3F1 mice (10 animals of each sex) were exposed
      to 1,2- dichloroethane in drinking water at 0, 500, 1,000, 2,000, 4,000, or 8,000
      ppm for 13 weeks. In addition, Groups of 10 F344/N rats of each sex were
      administered 1,2-dichloroethane in corn oil by gavage to compare toxicity
      resulting from bolus administration with that of continuous exposure in drinking
      water. Gavage doses of 1,2-dichloroethane were within the range of daily doses
      resulting from exposure in drinking water. No compound-related deaths occurred in
      any of the rat strains exposed to 1,2-dichloroethane in drinking water. Weight
      gain depression was common in each sex of all three rat strains in the 4,000 and
      8,000-ppm groups throughout the studies. Water consumption was decreased by 50%
      60% with increasing dose for all exposed male and female rats regardless of
      strain. Kidney and liver weights were increased in dosed rats of all three
      strains. No chemical-related lesions were observed except for a dose- related
      incidence of renal tubular regeneration in female F344/N rats. Nine of 10 female
      mice exposed to 8,000 ppm 1,2-dichloroethane in drinking water died before the
      end of the study. Mean body weights of males at 500 ppm or more and females at
      1,000 ppm or more were lower than those of controls throughout most of the
      studies. Kidney weights were significantly increased for dosed males and females.
      Renal tubular cell regeneration was seen in males at 8,000 ppm; at 4,000 ppm,
      minimal regeneration was present in 8/10 male mice. All male F344/N rats that
      received 240 or 480 mg/kg and 9/10 females that received 300 mg/kg 1,2
      dichloroethane by gavage died before the end of the studies. Mean body weights of
      the highest dose males and females were lower than those of vehicle controls
      throughout the studies. Liver and kidney weights were increased for dosed males
      and females; however, no compound-related lesions were observed. Necrosis of the
      cerebellum, hyperplasia, inflammation, and mineralization of the forestomach, and
      necrosis of the thymus were seen in animals that died or were killed in moribund
      condition. Rat strain differences in susceptibility to 1,2-dichloroethane
      toxicity were not apparent at the drinking water concentrations used in these
      studies; only female F344/N rats exhibited mild chemical related renal lesions.
      Male B6C3FI mice appeared to be more susceptible than rats to toxicity of 1,2
      dichloroethane administered in drinking water; renal tubule regeneration was
      observed in male mice in the 4,000- and 8,000-ppm groups. The higher toxicity in
      mice was likely due to higher water consumption, resulting in up to tenfold
      higher doses to mice than to rats. 1,2-Dichloroethane administered in drinking
      water resulted in less toxicity to F344/N rats than administration of similar
      doses by gavage. Synonyms: Freon 150; Brocide; Dutch liquid; Dutch oil. (NOTE:
      These studies were supported in part by funds from the Comprehensive
      Environmental Response, Compensation, and Liability Act trust fund (Superfund) by
      an interagency agreement with the Agency for Toxic Substances and Disease
      Registry, U.S. Public Health Service.)

PMID- 12209165
TI  - NTP technical report on the toxicity studies of Acetone in F344/N Rats and B6C3F1
      Mice (Drinking Water Studies) (CAS No. 67-64-1).
AB  - Toxicity studies were conducted by administering acetone (greater than 99%percnt;
      pure) in drinking water to groups of F344/N rats and B6C3F1 mice of each sex for
      14 days or 13 weeks. Fourteen-Day Studies: All rats and mice receiving
      concentrations as high as 100,000 ppm acetone in drinking water lived to the end
      of the 14-day studies. The mean body weights of male rats receiving 50,000 or
      100,000 ppm and female rats given 100,000 ppm were lower than those of controls.
      Body weights of all groups of mice were similar. Kidney and liver weight to body
      weight ratios for exposed rats and mice were greater than those for controls.
      Histopathologic changes were not seen in these organs in rats or in the kidney in
      mice. Centrilobular hepatocellular hypertrophy was noted in male and female mice
      receiving 20,000 and 50,000 ppm acetone, respectively. Thirteen-Week Studies: All
      rats lived to the end of the 13-week studies (drinking water concentrations as
      high as 50,000 ppm). The final mean body weights of rats receiving 50,000 ppm
      were 19%percnt; lower than that of controls for males and 7%percnt; lower for
      females. Water consumption by all rats that received 50,000 ppm acetone and
      females that received 20,000 ppm or more was notably lower than that by controls.
      Liver and kidney weight to body weight ratios were increased for male and female
      rats receiving 20,000 ppm or greater. Caudal and right epididymal weights and
      sperm motility were decreased for male rats given 50,000 ppm, and the percentage
      of abnormal sperm was increased. Leukocytosis and thrombocytopenia were observed
      at 20,000 ppm and above (males and females), and reticulocytopenia and
      erythrocytopenia were seen at 5,000 ppm and above (males). These changes, in
      addition to increase in erythrocyte size (MCV), are consistent with macrocytic
      anemia. Splenic pigmentation (hemosiderosis) noted in dosed male rats was
      apparently related to these changes. The increased incidence and severity of
      nephropathy observed in dosed male rats were considered the most prominent
      chemically related findings in this study. All mice lived to the end of the 13
      week studies (drinking water concentrations up to 20,000 ppm for males and up to
      50,000 ppm for females). The final mean body weights of dosed and control mice
      were similar. Water consumption by female mice that received 50,000 ppm acetone
      was notably lower than that by controls. The absolute liver weight and the liver
      weight to body weight ratio were significantly increased for females receiving
      50,000 ppm, and the absolute spleen weight and the spleen weight to body weight
      ratio were significantly decreased. Results from the hematologic analyses did not
      show any biologically significant effects. Centrilobular hepatocellular
      hypertrophy of minimal severity was seen in 2110 female mice receiving 50,000
      ppm. No compound-related lesions were found in male mice. In summary, the results
      from these studies show that acetone is mildly toxic to rats and mice when
      administered in drinking water for 13 weeks. Minimal toxic doses were estimated
      to be 20,000 ppm acetone for male rats and male mice and 50,000 ppm acetone for
      female mice. No toxic effects were identified for female rats. The testis,
      kidney, and hematopoietic system were identified as target organs in male rats,
      and the liver was the target organ for male and female mice. Synonyms: 2
      propanone; dimethyl ketone; pyroacetic acid. (NOTE: These studies were supported
      in part by funds from the Comprehensive Environmental Response, Compensation, and
      Liability Act trust fund (Superfund) by an interagency agreement with the Agency
      for Toxic Substances and Disease Registry, U.S. Public Health Service.)

PMID- 12209166
TI  - NTP technical report on the toxicity studies of of n-Hexane in B6C3F1 Mice
      (Inhalation Studies) (CAS No. 110-54-3).
AB  - Thirteen-week inhalation toxicity studies of n-hexane were conducted with B6C3F1
      mice of each sex exposed to 0, 500, 1,000, 4,000, or 10,000 ppm, 6 hours per day,
      5 days per week or to 1,000 ppm, 22 hours per day (referred to as 1,000c), 5 days
      per week. All mice lived to the end of the studies. The final mean body weights
      of mice exposed to 1,000c ppm or 10,000 ppm were 10% or 17% lower than that of
      the controls for males and 0% or 6% lower for females. Hematologic analyses were
      performed on whole blood samples collected at the end of the 13-week exposure.
      Segmented neutrophils were significantly increased in male mice exposed to 10,000
      ppm. A battery of behavioral measurements was conducted on mice, and the only
      parameter affected was locomotor activity, which was decreased in female mice at
      1,000c ppm and 10,000 ppm. The test battery performed included forelimb and hind
      limb grip strength, motor activity and exploratory behavior, acoustic startle
      response, foot splay, and analgesia response. Compound-related lesions of the
      nasal turbinates were seen in all groups of exposed mice except males exposed to
      500 or 4,000 ppm. At the 10,000-ppm concentration, nasal lesions included
      inflammatory, erosive, and regenerative lesions of the olfactory and respiratory
      epithelium; luminal exudation and metaplastic lesions of the olfactory
      epithelium; and fibrosis of the submucosa. Lymphoid hyperplasia of the mandibular
      lymph nodes and neutrophilic hyperplasia of the bone marrow were also seen. At
      lower concentrations, lesions were not present in all mice and were limited to
      minimal regeneration or metaplasia of the olfactory epithelium. A few paranodal
      swellings in the teased fibers of the tibial nerve were observed in 3/4 males and
      3/4 females exposed to 10,000 ppm, 3/4 males and 3/4 females exposed to 1,000c
      ppm, and 0/4 male and 0/4 female controls; the severity of the lesions was
      minimal. Neither segmental demyelination nor distal axonal degeneration was seen.
      Exposure of mice to n-hexane at concentrations up to 10,000 ppm resulted in only
      minimal toxicity. Paranodal swellings seen in nerves at 1,000c ppm and at 10,000
      ppm were considered to be minimal nerve damage that would not result in
      paralysis. Exposure- related lesions of the nasal cavity occurred after n-hexane
      exposure, but minimal or no effects were seen at 1,000 ppm or below. Synonyms:
      Hexyl hydride. (NOTE: These studies were supported in part by funds from the
      Comprehensive Environmental Response, Compensation, and Liability Act trust fund
      (Superfund) by an interagency agreement with the Agency for Toxic Substances and
      Disease Registry, U.S. Public Health Service.)

PMID- 12209167
TI  - NTP technical report on the toxicity studies of Hexachloro-1,3-butadiene in
      B6C3F1 Mice (Feed Studies) (CAS No. 87-68-3).
AB  - Two-week and 13-week toxicity studies of hexachloro-1,3-butadiene incorporated in
      the diet were conducted in B6C3F1 mice. Groups of five mice of each sex received
      diets containing 0, 30, 100, 300, 1,000, or 3,000 ppm hexachloro-1,3-butadiene
      for 15 days. Toxic responses in the 2-week studies, primarily in the higher dose
      groups, included abnormal clinical signs (lethargy, hunched posture, rough hair
      coats, light sensitivity, and/or in coordination), deaths (all mice in the two
      highest dose groups died by day 7), body and organ weight depression, and gross
      and histopathologic changes. The most prevalent microscopic lesion, seen in all
      hexachloro-1,3-butadiene-dosed mice, was renal tubular cell necrosis and/or
      regeneration. Regeneration was seen in lower dose groups. In addition to kidney
      lesions, histopathologic changes were also seen in the liver (hepatocyte
      necrosis, cytoplasmic vacuolization), lymphoid tissues (lymph node necrosis,
      depletion), and testis (seminiferous tubule giant cells) of mice in the two
      highest dose groups which died during the first week of the studies. Thirteen
      week studies were conducted in which groups of 10 mice per sex received 0,1,
      3,10, 30, or 100 ppm hexachloro-1,3-butadiene in feed (corresponding to doses of
      0, 0.1, 0.4, 1.5, 4.9, or 16.8 mg/kg per day for males and 0.2, 0.5, 1.8, 4.5, or
      19.2 mg/kg per day for females). No compound-related clinical signs or deaths
      were observed. Compared with controls, body weight gain was reduced in males
      receiving 30 and 100 ppm (-49% and -56%, respectively) and females receiving 100
      ppm (-47%). Kidney weights were reduced in the males receiving 30 and 100 ppm and
      females receiving 100 ppm. A compound-related increase in tubular cell
      regeneration in the renal cortex occurred in male and female mice. This lesion,
      characterized by a diffuse increase in basophilia of the tubular epithelial
      cytoplasm and an increase in the number of nuclei, increased in severity with
      increased dose. The motility of sperm from dosed mice was lower, though not dose
      related, than that from controls. Female mice were more susceptible to the
      toxicity of hexachloro-1,3-butadiene than male mice. Based on the histopathologic
      evaluations, the no-observed-adverse-effect level appeared to be 10 ppm for the
      male mice in this 13-week study; no such level was identified for the female
      mice. Synonyms: HCBD; hexachlorobutadiene; 1,1,2,3,4,4-hexachloro-1,3- butadiene;
      perchlorobutadiene; C 46; Dolen-Pur, (NOTE: These studies were supported in part
      by funds from the Comprehensive Environmental Response, Compensation, and
      Liability Act trust fund (Superfund) by an interagency agreement with the Agency
      for Toxic Substances and Disease Registry, U.S. Public Health Service.)

PMID- 12209168
TI  - NTP technical report on the toxicity studies of Methyl Ethyl Ketone Peroxide (CAS
      No. 1338-23-4) in Dimethyl Phthalate (CAS No. 131-11-3) (45:55) Administered
      Topically in F344/N Rats and B6C3F1 Mice.
AB  - Methyl ethyl ketone peroxide (MEKP) is an unstable organic peroxide used in the
      manufacture of acrylic resins, as a hardening agent for fiberglass-reinforced
      plastics, and as a curing agent for unsaturated polyester resins. It is
      commercially available as a 40% to 60% solution in dimethyl phthalate (DMP).
      Because exposure to MEKP is typically through dermal contact, 2-week and 13-week
      toxicity studies were conducted by topical application of MEKP in DMP (45:55 w/w)
      to the clipped dorsal region of male and female Fischer 344/N rats and mice.
      Animals were evaluated for histopathology and for reproductive endpoints. In
      vitro genetic toxicity studies of MEKP included assessments of mutagenicity in
      Salmonella typhimurium and in mouse lymphoma L5178Y cells and analysis of
      chromosomal aberrations and sister chromatid exchanges in Chinese hamster ovary
      cells. In addition, the peripheral blood of mice from the 13-week study was
      evaluated in the micronucleus assay. In the 2-week studies, groups of 5 animals
      of each species and sex were administered MEKP in DMP for 5 days per week at
      doses of 50.6, 101.3, 202.5, 405, and 810 mg/kg body weight per day for rats and
      112.5, 225, 450, 900, and 1800 mg/kg body weight per day for mice. Control groups
      received DMP or no treatment. No rats died during the studies, but at least 1
      mouse in each group receiving MEKP died. Body weight gains of rats decreased with
      increasing doses of MEKP; body weight gains of mice were not affected by
      treatment. The primary effects of topical administration of MEKP in both rats and
      mice were an extensive coagulative necrosis of the epidermis and dermis, variable
      degrees of inflammation of the adnexa, and epidermal regeneration and hyperplasia
      at the application site. Lesions considered secondary to the dermal lesions
      included increased hematopoiesis in the spleen in rats and mice and increased
      myeloid hyperplasia of the bone marrow in mice, primarily at the higher doses.
      Mice showed a marked, dose-related increase in liver weight. In the 13-week
      dermal studies, groups of 10 rats and 10 mice of each sex were administered MEKP
      in DMP for 5 days per week at doses of 1.07, 3.57, 10.7, 35.7, and 107 mg/rat and
      0.357, 1.19, 3.57, 11.9, and 35.7 mg/mouse. All high-dose mice, 3 high-dose
      female rats, and 1 female mouse in the 11.9 mg/animal group died or were
      sacrificed during the first week of the studies. Skin lesions similar to those
      seen in the 2-week studies were judged of sufficient severity to warrant early
      termination of surviving rats and mice in the 2 highest dose groups. All rats and
      mice in the remaining dose groups survived to the end of the studies, and weight
      gains were generally lower with increasing doses of MEKP. Skin lesions at the
      application site for the remaining animals (rats and mice) in the 10.7 mg/rat and
      3.57 mg/mouse dose groups involved a spectrum of necrosis, inflammation, and
      acanthosis (epidermal hyperplasia). Lesions in the lower dose groups were limited
      to acanthosis and hyperkeratosis in rats (1.07 and 3.57 mg/rat) and acanthosis in
      mice (0.357 and 1.19 mg/mouse). While splenic and bone marrow lesions similar to
      those described in the 2-week studies were seen in animals that died early in the
      13-week studies and in the rats and mice that showed ulcerative or necrotic
      injury, no other systemic changes were noted in animals that did not show
      ulcerative skin lesions. In genetic toxicity studies, MEKP in DMP (45:55 w/w) was
      not mutagenic in Salmonella typhimurium strains TA100, TA1535, TA1537, or TA98,
      with or without S9activation. A positive response was obtained in the mouse
      lymphoma assay for induction of trifluorothymidine resistance in L5178Y cells
      without S9. In cytogenetic tests with Chinese hamster ovary cells, MEKP induced
      sister chromatid exchanges and chromosomal aberrations, with and without S9. No
      increase in the frequency of micronucleated erythrocytes was observed in
      peripheral blood samples obtained from male and female mice at the termination of
      the 13-week toxicity study. In summary, topical administration of MEKP in DM of
      MEKP in DMP resulted in a spectrum of necrotic, inflammatory, and regenerative
      skin lesions limited to the application site. Histopathologic changes in the
      spleen and bone marrow were also seen in rats and mice with ulcerative skin
      lesions, and were considered a secondary response. A no-observed-adverse-effect
      level (NOAEL) for histopathologic skin lesions could not be determined from these
      studies, as lesions were observed with administration of daily doses as low as
      1.07 mg for rats and 0.357 mg for mice. Methyl Ethyl Ketone Peroxide Synonyms: 2
      Butanone Peroxide. Dimethyl Phthalate Synonyms: 1,2-Benzenedicarboxylic acid
      dimethyl ester; phthalic acid dimethyl ester; methyl phthalate; dimethyl 1,2
      benzene- dicarboxylate; DMP

PMID- 12209169
TI  - NTP technical report on the toxicity studies of Black Newsprint Inks Administered
      Topically to F344/N Rats and C3H Mice.
AB  - Toxicity studies were conducted by applying black newsprint inks or mineral oils
      to clipped skin of the dorsal interscapular area of C3H mice and F344/N rats of
      both sexes, to determine systemic and local effects. Four lots of both
      letterpress and offset types of newsprint ink were studied, either as composite
      mixtures or as individual lots. An industrial grade mineral oil, used as an
      extender for newsprint ink formulation, and USP medicinal grade mineral oil also
      were studied. Analyses for the presence of polycyclic aromatic hydrocarbons
      (PAHs) were conducted on composite ink mixtures and mineral oils; letterpress and
      offset ink mixtures were found to have cumulative concentrations of 206 and 105
      ppm, respectively; the concentration of PAHs in the printing ink mineral oil
      sample was 208 ppm, while none were detected in the USP grade mineral oil. In
      genetic toxicity studies, letterpress and offset newsprint ink composite mixtures
      were each mutagenic in Salmonella typhimurium strains TA98 and TA100 when tested
      in a preincubation protocol with added hamster liver S9. With rat liver S9,
      results for both inks were positive in strain TA98 and negative in strain TA100.
      Neither type of ink was mutagenic in the absence of S9 activation. In 30-day
      studies, 5 rats and mice per sex were given single, daily dermal applications of
      letterpress or offset newsprint inks, 5 days per week, for a total of 21 - 22
      applications. Dose groups for each type of ink received either the neat
      (undiluted) composite ink mixture, or the 3:1, 1:1, or 1:3 dilutions (ink:USP
      mineral oil), with a total dose volume of 100 (mice) or 250 (rats) &mgr;l. All
      animals survived until the end of the studies. Toxicity attributed to ink
      administration was limited to decreased body weight gains in female rats treated
      with neat and the 3:1 dilution of letterpress ink, and to scaliness at the site
      of application in 1 or more mice in each letterpress ink treatment group. As a
      result of grooming activity and the large amount of test chemical applied,
      chemicals were spread over the body, and there was evidence that some oral
      ingestion had occurred. In 13-week studies, various ink and mineral oil
      formulations were administered dermally to 10 rats and mice per sex. To prevent
      accumulation of inks and distribution over the body as seen in the 30-day
      studies, the frequency of application was reduced to twice weekly and the total
      dose volume was decreased to 20 microliters for mice and 50 microliters for rats.
      Treatment groups for rats consisted of letterpress ink mixture, offset ink
      mixture, printing ink mineral oil, USP mineral oil, and clipped, untreated
      controls. Groups of mice were administered each of the 4 individual lots of both
      letterpress and offset inks, the composite mixtures of each, and printing ink and
      USP mineral oils; clipped, untreated groups served as controls. All rats, all
      male mice, and all female mice except one administered offset ink-lot E survived
      to the end of the studies. Effects attributable to compound administration in
      rats were limited to decreased body weight gains in females treated with printing
      ink mineral oil and letterpress ink mixture, and increased liver and kidney
      weights in both males and females exposed to USP mineral oil; there were no local
      toxic effects at the site of application. In mice, there were no body weight
      effects, but liver weights were increased in most ink and mineral oil treatment
      groups of both sexes. Dermal toxicity was evidenced in mice by scaliness and
      irritation at the site of application of both sexes treated with USP mineral oil
      and letterpress ink-lot C. Microscopically, local toxicity at the site of
      application was observed in mice of all treatment groups and was characterized by
      acanthosis and inflammation. In summary, results of these studies indicate that
      topical administration of black newsprint inks and mineral oils produces local
      toxicity at the site of application in mice; toxic effects on the skin in this
      species are consistent with those of a primary cutaneous irritant. In rats,
      possible evidence for toxicity was limited to decreased body weight gains in
      females treated with letterpress ink formulations.

PMID- 12209170
TI  - NTP technical report on the toxicity studies of Glyphosate (CAS No. 1071-83-6)
      Administered In Dosed Feed To F344/N Rats And B6C3F1 Mice.
AB  - Glyphosate is a systemic, broad-spectrum, post-emergence herbicide used for non
      selective weed control. It was selected for study because of its widespread use,
      potential for human exposure, and the lack of published reports concerning
      comprehensive toxicity or carcinogenicity evaluations. Chemical disposition, 13
      week toxicity, and mutagenicity studies of glyphosate were conducted. In
      disposition studies, male F344/N rats were administered an oral dose (5.6 or 56
      mg/kg) of 14C-glyphosate. Blood, urine, fecal, and tissue samples were collected
      and analyzed for radioactivity. Within 72 hours after glyphosate dosing, 20-30%
      of the administered radioactivity was eliminated via urine, 70-80% via feces, and
      about 1% of the radioactivity remained in the tissues. Studies following oral,
      intravenous, and intraperitoneal administration of glyphosate indicated that the
      urinary radioactivity represented the amount of glyphosate absorbed and that the
      fecal radioactivity represented the amount unabsorbed from the gastrointestinal
      tract. In the 13-week toxicity studies, groups of 10 male and female F344/N rats
      and B6C3F1 mice were administered glyphosate in feed at 0, 3125, 6250, 12500,
      25000, or 50000 ppm. Glyphosate administration induced increases in serum bile
      acids, alkaline phosphatase, and alanine aminotransferase activities in rats,
      suggesting mild toxicity to the hepatobiliary system. Clinical pathology
      measurements were not performed with mice. No histopathologic lesions were
      observed in the livers of rats or mice. There was no evidence of adverse effects
      on the reproductive system of rats or mice. Cytoplasmic alteration was observed
      in the parotid and submandibular salivary glands of rats and parotid salivary
      glands in mice. The salivary gland effects of glyphosate were demonstrated to be
      mediated through an adrenergic mechanism which could be blocked by the adrenergic
      antagonist, propanolol. Glyphosate was not mutagenic in Salmonella, and did not
      induce micronuclei in mice. The no-observed-adverse-effect level (NOAEL) for the
      salivary gland lesions was 3125 ppm in the diet for mice. A NOAEL could not be
      determined from the rat study. Synonyms: Glyphosate, technical grade; Glycine, N
      (phosphonomethyl); N-phosphono-methyl glycine; N-(phosphonomethyl)glycine; MON
      0573; MON 2139.

PMID- 12209171
TI  - NTP technical report on the toxicity studies of t-Butyl Perbenzoate (CAS No. 614
      45-9) Administered By Gavage To F344/N Rats And B6C3F1 Mice.
AB  - t-Butyl perbenzoate (t-BP) is a relatively stable, lipid-soluble, organic
      peroxide widely used in the polymer industry. Studies were designed to determine
      the stability of t-BP in various biological media, its dermal absorption and
      distribution in intact animals, and the toxicity of t-BP when administered orally
      to both sexes of rats and mice for 14 days or 13 weeks. In genetic toxicity
      studies, t-BP was found to be mutagenic in Salmonella typhimurium strains TA100,
      TA1537, and TA98, with and without metabolic activation. t-BP-induced sister
      chromatid exchange and chromosomal aberrations in Chinese hamster ovary cells in
      vitro but did not induce formation of micronuclei in peripheral blood in mice in
      the 13-week studies. Stability studies indicated t-BP was sufficiently stable in
      dose formulations to permit administration by gavage, intravenous injection, or
      dermally. However, t-BP degraded rapidly in blood, stomach contents, and liver
      homogenates, or in the presence of glutathione. Initial degradation products of t
      BP are benzoic acid and t-butanol. Studies of t-BP disposition determined that
      approximately 16% of dermal doses administered to rats was absorbed and rapidly
      eliminated without tissue accumulation. Similarly, t-BP given intravenously was
      rapidly degraded and eliminated, primarily in urine, with no apparent
      accumulation in any tissue. Because dermal absorption was considered insufficient
      to administer a toxic dose, studies of t-BP toxicity were performed using gavage
      administration. Results of 14-day toxicity studies with 5 animals of each sex of
      rats and mice indicated that t-PB, administered by gavage in corn oil in doses
      ranging from 70 to 1112 mg/kg, produced no marked signs of systemic toxicity.
      Toxicity in mice, attributable to t- BP, was limited largely to increased stomach
      weights in males and females receiving the highest doses. This toxicity was
      characterized by forestomach epithelial hyperplasia, ulceration, and acute
      inflammation. Equimolar doses of the degradation products of t-BP (t-butanol and
      benzoic acid) also were administered in the 14-day studies to determine if t-BP
      toxicity could be attributed to the parent compound or products of its chemical
      degradation and/or metabolism. Results of these studies indicated that equimolar
      doses of t-butanol were not toxic in either sex or species. Some systemic
      toxicity of benzoic acid was observed in both sexes of mice, but not rats,
      receiving the highest dose (642 mg/kg). Toxicity was evidenced by the poor
      condition of dosed animals and in several deaths during the first week of the
      study. No lesions were observed microscopically, and it is speculated that this
      toxicity may have been due to acidosis. In the 13-week studies, t-BP was
      administered by gavage in water to 10 rats and 10 mice of each sex, at doses up
      to 500 mg/kg. The doses resulted in depressed body-weight gains in the highest
      dose groups and in dose-dependent increases in forestomach weights. Hyperplasia
      of the forestomach mucosa was observed in most groups of dosed rats and increased
      in severity with dose. Hyperplasia was characterized by increased cellularity and
      basophilia of the squamous epithelium with variable degrees of hyperkeratosis. t
      BP toxicity observed in mice was limited to increased forestomach weight in most
      dose groups and to less dramatic increases in glandular stomach weight in mice
      receiving the highest doses. Forestomach toxicity was characterized by dose
      dependent increases in hyperplasia of the squamous epithelium in all mice except
      those in the low dose group. Based on the results presented in this report, it is
      concluded that the no-observed-adverse-effect-level (NOAEL) for t-BP to induce
      forestomach lesions in rats and mice is approximately 30 mg/kg. Systemic toxicity
      was not observed in either species with oral doses as high as 1112 mg/kg.
      Synonyms: Benzenecarboperoxoic acid; 1,1-dimethylester; Esperox 10; Trigonox C; t
      BP.

PMID- 12209172
TI  - NTP technical report on the toxicity studies of para-Chloro-alpha,alpha,alpha
      Trifluorotoluene (CAS NO: 98-56-6) Administered in Corn Oil and alpha
      Cyclodextrin to F344/N Rats and B6C3F1 Mice in 14-Day Comparative Gavage Studies.
AB  - p-Chloro-alpha,alpha,alpha trifluorotoluene (CTFT) is a volatile, aromatic liquid
      used as a chemical intermediate in the manufacture of dinitroaniline herbicides.
      To evaluate the toxicity of CTFT, groups of F344/N rats and B6C3F1 mice of each
      sex were administered CTFT by gavage once a day for 14 consecutive days in either
      corn oil or in an experimental molecular complex vehicle, a-cyclodextrin (alpha
      CD). Dose levels selected for CTFT with the alpha-CD vehicle were 10, 50, and 400
      mg/kg; dose levels used with the corn oil vehicle were 10, 50, 400, and 1000
      mg/kg. The toxicokinetics of CTFT also were compared by gavage with the different
      vehicles and by i.v. administration. In genetic toxicity studies, CTFT was not
      mutagenic in Salmonella typhimurium. The elimination of an intravenous dose of
      CTFT from blood is best described by a triexponential equation. The data best fit
      a 3-compartment kinetic model with a very rapid distribution phase. A
      biexponential equation was found to best fit the elimination of CTFT from blood
      following a gavage dose in either corn oil or an aqueous molecular complex
      suspension, alpha-CD. However, the biological half-life (t 1/2) was the same in
      both routes, approximately 20 hours. Absorption of CTFT from the alpha-CD vehicle
      was found to be much faster than from corn oil. The average t 1/2 of the
      absorption phase for a 10 mg/kg dose of CTFT in the alpha-CD and corn oil
      vehicles was 7 and 150 minutes, respectively. Despite the differences in
      absorption, no statistical difference was observed in the calculated area under
      blood concentration versus time curves (AUC) obtained from rats dosed with CTFT
      in either vehicle. Blood concentrations of CTFT were proportional to dose, at
      levels as high as 400 mg/kg in both vehicles. The bioavailability of CTFT was
      shown to be complete in both vehicles, through comparing the AUC following oral
      and i.v. dosing. In 14-day toxicity studies, 1 of 10 female rats given the top
      dose of 1000 mg/kg CTFT in corn oil died on day 8; no deaths of male rats or of
      mice of either sex were attributable to the administration of CTFT. Body weight
      gains in all groups of rats and mice were similar with the exception of the top
      dose (1000 mg/kg) groups of male and female rats, which lost weight during the
      first week and resumed weight gain during the second. CTFT was found to
      accumulate in the kidneys of male rats, and there was a linear relationship
      between the kidney CTFT concentrations and the kidney levels of a2u-globulin, as
      determined by an ELISA assay. Microscopic changes in male rats included a dose
      related toxic nephropathy consistent with that previously described as "hyaline
      droplet nephropathy." Dosed male and female rats also had hepatocyte hypertrophy
      and cytoplasmic vacuolization of the adrenal cortex. Clinical pathology findings
      suggested a mild anemia and cholestasis in rats. In contrast to rats, mice did
      not show appreciable CTFT concentrations in any tissue evaluated, suggesting a
      more rapid elimination of the chemical. However, hepatocellular hypertrophy, and
      clinical pathology findings consistent with cholestasis and mild liver injury,
      were noted in mice in the 400 and 1000 mg/kg dose groups. These studies
      demonstrated that oral doses of CTFT of 400 mg/kg or higher caused liver
      hypertrophy in rats and mice and adrenal changes in rats. Doses of 50 mg/kg or
      higher caused "hyaline droplet nephropathy" in male rats. The results were
      similar with CTFT administered either in corn oil or in alpha-CD (although
      absorption of CTFT was somewhat more rapid with alpha-CD), suggesting that alpha
      CD may be an appropriate vehicle for toxicity studies with other chemicals.
      Synonyms: CTFT; p-Chloro-4-(trifluoromethyl) benzene; (p-chlorophenyl)
      trifluoromethane; 4-chlorobenzotrifluoride; Benzene, 1-chloro-4-(trifluoromethyl)
      ; p-(trifluoromethyl) chloro-benzene; p-chlorobenzotrifluoride; p-chlorotri
      fluoromethylbenzene; p-trifluoromethylphenyl chloride; parachloro
      alpha,alpha,alpha trifluorotoluene; parachlorobenzotrifluoride;
      parachlorotrifluoro-methylbenzene.

PMID- 12209173
TI  - NTP technical report on the toxicity studies of Trinitrofluorenone (Cas No. 129
      79-3) Administered by Dermal Application and Dosed Feed to F344/N Rats and B6C3F1
      Mice.
AB  - Trinitrofluorenone (TNF) is a major component of a toning formulation that at one
      time was used widely in certain photocopy processes. Because the principal route
      of exposure of humans to TNF probably would be dermal, studies were conducted to
      compare chemical absorption, distribution, excretion, and tissue retention, as
      well as toxicity in 14-day studies, by oral and dermal routes of exposure.
      Further, 13-week toxicity studies were carried out with TNF incorporated into the
      feed of rats and mice of both sexes. In genetic toxicity evaluations, TNF was
      found to be mutagenic in Salmonella typhimurium, with and without metabolic
      activation. In disposition and metabolism studies, excretion patterns following
      oral administration of radiolabeled TNF (in doses ranging between 1 and 100 mg/kg
      body weight) were similar; 20% and 70% of the administered dose appeared in urine
      and feces, respectively, during the first 72 hours. Residual radiolabel in
      tissues comprised less than 1% of the dose. The appearance in the feces of 60-70%
      of a 1 mg/kg i.v. dose provided evidence for substantial biliary excretion of
      TNF; studies of the radiolabeled materials extracted from urine and feces
      suggested that glucuronidation is a major biotransfomation of TNF and its
      metabolites. In the dermal exposure studies, groups of 5 F344/N rats and 5 B6C3F1
      mice of each sex were administered TNF in acetone by topical application once a
      day, 5 days per week, for 14 days. Doses were 0, 7.5, 15, 30, 60, or 120 mg/kg
      body weight for rats and 0, 12.5, 25, 50, 100, or 200 mg/kg for mice. There were
      no deaths, no adverse clinical signs, and no gross or microscopic changes related
      to treatment in either species, except for discoloration of skin at the site of
      application. Disposition studies with female rats showed that less than 10% of a
      dermal dose of 47 mg and less than 3% of a dermal dose of 400 mg were available
      systemically. In contrast, toxicity was observed in the 14-day feeding studies
      with TNF. Groups of 5 rats and 5 mice of each sex were fed diets containing TNF
      at concentrations of 0, 500, 1600, 5000, 16000, or 50000 ppm. There were no
      deaths of rats or mice, but body weight gains of rats receiving 50000 ppm were
      reduced by as much as 45%. Animals receiving diets with 5000 ppm or higher TNF
      had a black discoloration of the skin and hair and enlarged and/or dark thyroid
      glands. Mild follicular cell hypertrophy and pigmentation of the epithelium and
      colloid were noted in the thyroid gland. Among mice, the brain and gallbladder
      were dark; the spleen of females was dark and also enlarged by hematopoiesis.
      Thymic lymphoid depletion and atrophy of the seminal vesicles were present in top
      dose male rats (50000 ppm). In 13-week studies, groups of 10 animals of each sex
      received diets containing TNF at concentrations of 0, 1000, 2000, 4000, 8000, or
      16000 ppm for rats, and 0, 3125, 6250, 12500, 25000, or 50000 ppm for mice. No
      rats died, but the deaths of several mice in the 50000 ppm groups indicated a
      possible relation to TNF ingestion. Body weight gains of dosed rats were lower
      than controls and were dose-related. Top-dose male mice gained markedly less
      weight than controls. A mild macrocytic anemia and increase in methemoglobin was
      present in dosed rats at the end of the study. In both species, there was a
      widespread occurrence of a dark brown pigment in dosed animals, with little
      evidence of toxicity related to the pigment accumulation. Other treatment-
      related effects in male rats included mesenteric vascular inflammation, renal
      inflammation, testicular degeneration with reduced sperm count and motility,
      splenic hematopoiesis, and oval cell hyperplasia, cytoplasmic alteration, and
      mixed cell foci in the liver. Top-dose female rats had centrilobular hepatocyte
      cytoplasmic alteration and splenic hematopoiesis. Dosed mice of both sexes showed
      cystic degeneration of the thyroid gland, liver hypertrophy, and splenic
      hematopoiesis. In summary, TNF caused a variety of lesions in oral feeding
      studies. The no-observed-adverse-effect-level (NOAEL) for microscopic ced-adverse
      effect-level (NOAEL) for microscopic changes other than pigment accumulation was
      1000 ppm for rats. A NOAEL could not be determined for mice from this study.
      Limited dermal absorption likely would prevent significant systemic toxicity
      resulting from contact of TNF with the skin. Synonyms: TNF; 2,4,7-trinitro-9H
      fluoren-9-one.

PMID- 12209174
TI  - NTP technical report on the toxicity studies of Castor Oil (CAS No. 8001-79-4) in
      F344/N Rats and B6C3F1 Mice (Dosed Feed Studies).
AB  - Castor oil is a natural oil derived from the seeds of the castor bean, Ricinus
      communis. It is comprised largely of triglycerides with a high ricinolin content.
      Toxicity studies with castor oil were performed by incorporating the material at
      concentrations as high as 10% in diets given to F344/N rats and B6C3F1 mice of
      both sexes for 13 weeks. Genetic toxicity studies also were performed and were
      negative for mutation induction in Salmonella typhimurium, for induction of
      sister chromatid exchanges or chromosomal aberrations in Chinese hamster ovary
      cells, and for induction of micronuclei in the peripheral blood erythrocytes of
      mice evaluated at the end of the 13-week studies. Exposure to castor oil at
      dietary concentrations as high as 10% in 13-week studies did not affect survival
      or body weight gains of rats or mice (10 per sex and dose). There were no
      biologically significant effects noted in hematologic analyses in rats. Mild
      increases in total bile acids and in serum alkaline phosphatase were noted at
      various times during the studies in rats receiving the higher dietary
      concentrations of castor oil. Liver weights were increased in male rats receiving
      the 10% dietary concentration and in male and female mice receiving diets
      containing 5% or 10% castor oil. However, there were no histopathologic lesions
      associated with these liver changes, nor were there any compound-related
      morphologic changes in any organ in rats or mice. No significant changes were
      noted in a screening for male reproductive endpoints, including sperm count and
      motility, and no changes were observed in the length of estrous cycles of rats or
      mice given diets containing castor oil. Thus, no significant adverse effects of
      castor oil administration were noted in these studies. Synonyms: Ricinus Oil, oil
      of Palma Christi, tangantangan oil, phorboyl, Neoloid. 

PMID- 12209175
TI  - NTP technical report on the toxicity studies of Toxicity Studies of Antimony
      Potassium Tartrate (CAS No. 28300-74-5) in F344/N Rats And B6C3F1 Mice (Drinking
      Water and Intraperitoneal Injection Studies).
AB  - Antimony potassium tartrate (APT) is a complex salt that until recently was used
      worldwide as an anti-schistosomal drug. APT was efficacious in humans only if
      administered intravenously at a near-lethal total dose of 36 mg/kg. Because
      unconfirmed epidemiologic studies suggested a possible association between APT
      treatment and bladder cancer, prechronic toxicity studies were initiated with APT
      to select a route of administration and appropriate doses in the event chronic
      studies were needed. To determine the most appropriate route for longer-term
      studies, toxicity and concentrations of tissue antimony were compared in F344/N
      rats and B6C3F1 mice that were administered APT in drinking water or by i.p.
      injection for 14 or 16 days. The animals were assigned to dose groups,
      5/sex/species. Drinking water doses, estimated by water consumption, were 0, 16,
      28, 59, 94, or 168 mg/kg in rats and 0, 59, 98, 174, 273, or 407 mg/kg in mice;
      i.p. doses were 0, 1.5, 3, 6, 11, or 22 mg/kg in rats and 0, 6, 13, 25, 50, or
      100 mg/kg in mice. APT was poorly absorbed and relatively nontoxic when given
      orally. There was no mortality or histopathological lesions in rats or mice
      receiving doses of APT as high as 168 or 273 mg/kg, respectively. One mouse in
      the highest dose group (407 mg/kg) died, and there were treatment-related lesions
      in the liver and forestomach of most mice in this dose group. In contrast, i.p.
      administration of the drug was much more toxic, resulting in the deaths of rats
      administered 22 mg/kg; kidney and liver lesions were found in these rats. In
      mice, i.p. administration of APT caused deaths and liver lesions at dose levels
      one-fourth of those that caused similar effects by oral administration. All male
      and female mice injected with 100 mg/kg APT died; half of the female mice given
      50 mg/kg APT died; additional deaths occurred with doses as low as 6 mg/kg.
      Hepatocellular necrosis and inflammation of the liver capsule were present in
      both sexes of mice in the 50 mg/kg dose groups. As a result of these findings, an
      i.p. dose regimen was selected for subsequent studies. Groups of ten male and
      female F344/N rats and B6C3F1 mice were given 0, 1.5, 3, 6, 12, or 24 mg/kg doses
      of APT 3 times per week for 13 weeks by i.p. injection. Rats were more sensitive
      than mice to the toxic effects of APT, exhibiting dose-related mortality and
      reduction in body weight. Four male rats in the 24 mg/kg dose died; body weights
      in both sexes of rats from this dose group and in male rats from the 12 mg/kg
      dose group were 10-20% below controls. No clinical signs of toxicity in the mice,
      nor gross or microscopic lesions, could be attributed to APT. Increased
      concentrations of antimony, considered to be dose-related, were detected in the
      blood, liver, kidney, spleen, and heart of rats, and in the liver and spleen of
      mice. In rats, hepatocellular degeneration and necrosis were associated with dose
      related elevations in activities of the liver-specific serum enzymes, sorbitol
      dehydrogenase and alanine aminotransferase. By alternating the site of abdominal
      injection and the days of treatment, mesenteric inflammation at the site of
      administration was minimized in the rats and mice, indicating that the i.p. route
      would be suitable for chronic studies. Hepatotoxicity in rats occurred in dose
      groups where there was little evidence of renal toxicity and no cardiac toxicity;
      thus, serial measurement of liver-specific serum enzyme activities may be useful
      to monitor the presence and progression of hepatocellular degeneration in longer
      term exposures. Synonyms: APT; Tartar emetic; tartrated antimony; tartarized
      antimony; potassium antimonyltartrate; Bis [MU-[2,3-dihydroxy- butanedioato(4-)
      O1, O2:O3, O4]]-diantimonate dipotassium trihydrate (stereoisomer). 

PMID- 12209176
TI  - NTP technical report on the toxicity studies of Ethylbenzene (Cas No. 100-41-4)
      in F344/N Rats and B6C3F1 Mice (Inhalation Studies).
AB  - Ethylbenzene is commonly used as a solvent and chemical intermediate and as an
      additive in some motor fuel formulations. Inhalation toxicology studies of
      ethylbenzene (99% pure) were conducted by exposing groups of F344/N rats and
      B6C3F1 mice of each sex to ethylbenzene vapor at chamber concentrations of 0,
      100, 250, 500, 750, or 1000 ppm, 6 hours per day, 5 days per week for 13 weeks.
      No rats or mice died during the 13-week exposure. Body weight gains were slightly
      lower in the high dose groups of male and female rats, but the differences were
      not statistically significant. Absolute and relative kidney, liver, and lung
      weights were increased in the exposed rats, while weight increases occurred only
      in the livers of exposed mice. Chemically related histopathologic changes were
      not observed in any tissues of rats or mice. No changes were observed in the
      evaluation of sperm or vaginal cytology in rats or mice. Ethylbenzene was not
      mutagenic in Salmonella and did not induce chromosomal aberrations or sister
      chromatid exchanges in Chinese hamster ovary (CHO) cells in vitro, though it did
      induce trifluorothymidine resistance in mouse lymphoma cells at the highest
      concentration tested. Micronuclei assays in peripheral blood of mice were
      negative. Thus, there appears to be only minimal evidence of toxicity in F344/N
      rats and B6C3F1 mice exposed to ethylbenzene by inhalation at concentrations as
      high as to 1000 ppm for 13 weeks. Synonyms: EB, ethyl benzene, ethylbenzol,
      phenylethane. (NOTE: These studies were supported in part by funds from the
      Comprehensive Environmental Response, Compensation, and Liability Act trust fund
      (Superfund) by an interagency agreement with the Agency for Toxic Substances and
      Disease Registry, U.S. Public Health Service.)

PMID- 12209177
TI  - NTP technical report on the toxicity studies of Cresols (CAS Nos. 95-48-7, 108-39
      4, 106-44-5) in F344/N Rats and B6C3F1 Mice (Feed Studies).
AB  - Cresols are monomethyl derivatives of phenol, and are found as constituents of
      coal tar, in various industrial solvents and resins, and in some essential oils.
      In 28-day toxicity studies, F344/N rats and B6C3F1 mice of both sexes were given
      o-cresol, m-cresol, p-cresol, or m/p-cresol (60:40) at concentrations from 300
      ppm to 30,000 ppm in the diet. In 90-day studies, o-cresol or m/p-cresol (60:40)
      were added to the diet in concentrations as high as 30,000 ppm to F344/N rats and
      20,000 ppm (o-cresol) or 10,000 ppm (m/p-cresol) to B6C3F1 mice. In the 28-day
      studies, all rats survived (5 per sex per dose), but some mice given o-cresol at
      30,000 ppm, or m-cresol or p-cresol at 10,000 ppm or 30,000 ppm died before the
      end of the studies. Feed consumption was depressed during the first study week in
      all high- dose groups of animals and weight gains were generally less than
      controls in groups given 10,000 or 30,000 ppm in the four 28-day studies.
      Increased relative liver weights and kidney weights were noted in both rats and
      mice given concentrations of cresols as low as 3,000 ppm. However, there were no
      consistent microscopic changes associated with these weight increases. Bone
      marrow hypoplasia and uterus, ovary and occasional mammary gland atrophy were
      seen primarily at the highest dietary concentration, but also at 10,000 ppm with
      certain cresols. An effect specific to the p- cresol and m/p-cresol studies was
      atrophy and regenerative changes in the nasal epithelia and forestomach,
      presumably a direct result of the irritant effects of the chemical or its vapors.
      Results of reproductive tissue evaluations and estrus cycle characterizations
      with o-cresol and m/p-cresol gave no indication of adverse effects to the male
      reproductive system, but the estrus cycle was lengthened in rats and mice
      receiving the higher concentrations of o-cresol and rats receiving m/p-cresol. In
      the 90-day studies, no deaths of rats (20 per sex per dose) or mice (10 per sex
      and dose) could clearly be related to administration of either o-cresol or m/p
      cresol. Hematology, clinical chemistry, and urinalysis results were generally
      unremarkable in all studies, although an accumulation of bile acids in high-dose
      rats was considered evidence of a deficit in hepatocellular function resulting
      from ingestion of the chemical. Results of microscopic analyses were consistent
      with findings in the 28-day studies, and revealed evidence of mild bone marrow
      hypocellularity in rats and forestomach hyperplasia in mice given diets
      containing the higher concentrations of o-cresol. Evidence of nasal irritation
      was present in rats and mice receiving feed containing m/p-cresol. Additional
      lesions in rats receiving m/p-cresol included bone marrow hypocellularity and
      uterine atrophy. The cresol isomers exhibited a generally similar pattern of
      toxicities in rats and mice. Dietary concentrations of 3,000 ppm appeared to be
      minimal effect levels for increases in liver and kidney weights and deficits in
      liver function. Histopathologic changes, including bone marrow hypocellularity,
      irritation to the gastrointestinal tract and nasal epithelia, and atrophy of
      female reproductive organs, occasionally occurred at 10,000 ppm, but were more
      common at the high-dose of 30,000 ppm. Synonyms: phenol, 2-methyl-(9CI); 2
      cresol; o-cresylic acid; 1-hydroxy-2-methylbenzene; 2-hydroxytoluene; o
      hydroxytoluene; 2-methylphenol; o-methylphenol; o-methylphenylol; o-oxytoluene;
      RCRA Waste Number U052; o-toluol; UN 2076; phenol, 3-methyl-(9CI); 3-cresol; m
      cresole; m-cresylic acid; 1-hydroxy-3-methylbenzene; 3-hydroxytoluene; m
      hydroxytoluene; m-kresol; 3-methylphenol; m-methylphenol; m-oxytoluene; RCRA
      Waste Number U052; m-toluol; UN 2076; phenol, 4-methyl- (9CI); 4-cresol; p
      cresylic acid; 1-hydroxy-4-methylbenzene; 4-hydroxytoluene; p-hydroxytoluene; p
      kresol; 1-methyl-4-hydroxybenzene; p-methylhydroxy- benzene; 4-methylphenol; p
      methylphenol; p-oxytoluene; RCRA Waste Number U052; p-toluol; p-tolyl alcohol; UN
      2076. (NOTE: These studies were supported in part by funds from the Comprehensive
      Environmental Response, Compensation, and Liability Act trust fund (Superfund) by
      an interagency agreement with the Agency for Toxic Substances and Disease
      Registry, U.S. Public Health Service.)

PMID- 12209178
TI  - NTP technical report on the toxicity studies of Tetrachlorophthalic Anhydride
      (CAS No. 117-08-8) Administered by Gavage to F344/N Rats and B6C3F1 Mice.
AB  - Tetrachlorophthalic anhydride (TCPA) is primarily used as a flame retardant in
      plastics. Toxicology studies were conducted by administering TCPA by oral gavage
      to F344/N rats and B6C3F1 mice for 13 weeks. Evaluations included histopathology,
      clinical pathology, and analyses of reproductive system parameters. The genetic
      toxicity of TCPA was assessed with in vitro tests of mutagenicity in Salmonella
      typhimurium and induction of sister chromatid exchanges and chromosomal
      aberrations in Chinese hamster ovary cells; sister chromatid exchanges and
      chromosomal aberrations were also determined in mouse bone marrow cells following
      in vivo exposure. The ability of TCPA to induce sex-linked recessive lethal
      mutations was also studied in vivo in Drosophila melanogaster. Groups of 10 rats
      and 10 mice of each sex received TCPA in corn oil vehicle by oral gavage (5
      days/week) at doses of 0, 94, 187, 375, 750, and 1500 mg/kg. The deaths of 5 male
      rats and 1 female rat in the 1500 mg/kg dose group and 1 female rat in the 750
      mg/kg dose group were considered due to chemical toxicity. Mean final body
      weights and body weight gains were depressed in male rats in the 375, 750, and
      1500 mg/kg groups and in all groups of female rats receiving TCPA. Relative liver
      weights were slightly increased in males and females at doses of 187 mg/kg and
      higher, although a dose relationship was not apparent. Heart weights of surviving
      male rats in the high-dose group were also increased. Male and female rats
      exhibited dose-dependent increases in kidney weights and in the incidence and
      severity of renal tubule necrosis and/or dilation. No clinical pathology changes
      were clearly associated with chemical exposure. There were no chemical-related
      effects on survival, body weights, or organ weights in dosed mice. No chemical
      related lesions were identified in organs examined microscopically. Decreases in
      red blood cell parameters consistent with a mild, poorly regenerative anemia were
      the only evidence of possible compound toxicity in dosed mice. Sperm morphology
      and vaginal cytology evaluations in rats and mice revealed no adverse changes
      related to TCPA exposure. In genetic toxicology studies, TCPA, tested with and
      without exogenous metabolic activation (S9), was not mutagenic in Salmonella
      typhimurium and did not induce sister chromatid exchanges or chromosomal
      aberrations in Chinese hamster ovary cells. In the Drosophila melanogaster sex
      linked recessive lethal test, TCPA gave equivocal results when administered by
      feeding and negative results when administered by injection. No induction of
      chromosomal aberrations was observed in bone marrow cells of mice 17 hours after
      intraperitoneal injection of TCPA, although an increase in sister chromatid
      exchanges was detected in these cells 23 hours after injection. In summary, clear
      evidence of organ toxicity following administration of TCPA in corn oil by gavage
      for 13 weeks was limited to the kidney of rats. The no-observed-adverse-effect
      level for histopathologic lesions in this tissue was not achieved with doses as
      low as 94 mg/kg per day. No significant adverse effects were seen in mice given
      doses as high as 1500 mg/kg per day for 13 weeks. Synonyms: 4,5,6,7-Tetrachloro
      1,3-isobenzofurandione; 1,3-dioxy- 4,5,6,7-tetrachloroisobenzofuran; 3,4,5,6
      tetrachloro-1,2-benzene- dicarboxylic anhydride; niagathal; tetrathal.

PMID- 12209179
TI  - NTP technical report on the toxicity studies of Riddelliine (CAS No. 23246-96-0)
      Administered by Gavage to F344 Rats and B6C3F1 Mice.
AB  - Riddelliine is a naturally occurring pyrrolizidine alkaloid, a class of compounds
      occurring in rangeland plants of the genera Crotalaria, Amsinckia, and Senecio.
      Two-week and 13-week rodent toxicity studies of riddelliine were conducted
      because riddelliine can be a contaminant of foodstuffs, such as meat, grains,
      seeds, milk, herbal tea, and honey. In addition to histopathology, evaluations
      included clinical pathology and reproductive toxicity. In vitro genetic toxicity
      studies included assessments of mutagenicity in Salmonella typhimurium and of the
      induction of chromosomal aberrations and sister chromatid exchanges in Chinese
      hamster ovary cells. Riddelliine was also evaluated in vivo for the induction of
      micronuclei in mouse bone marrow and in peripheral blood and for the induction of
      S-phase synthesis and unscheduled DNA synthesis in the liver of rats and mice. In
      the 2-week studies, groups of five male and five female F344/N rats and B6C3F1
      mice were administered riddelliine in 0.1 M phosphate buffer by gavage at dose
      levels of 0, 0. 33, 1.0, 3.3, 10, or 25 mg/kg body weight five times per week,
      for a total of 12 doses. Four of five male rats in the 25 mg/kg group died or
      were killed moribund before the end of the study. Mean body weight gains of male
      rats in the 10 and 25 mg/kg groups were depressed. No deaths or body weight
      effects were observed in female rats. Male rats had dose-related hemorrhagic
      centrilobular hepatic necrosis, hepatocytic karyomegaly and cytologic
      alterations, pulmonary hemorrhage and/or edema, splenic extramedullary
      hematopoiesis, and pancreatic edema. Female rats exhibited fewer and less severe
      lesions than identically treated male rats. Heart weights of treated male and
      female rats were lower than those of the controls. No deaths or effects on body
      weight were observed in treated mice. Dose-related increases in absolute and
      relative liver weights and increased incidences of hepatic cytomegaly were the
      only treatment-related findings in male and female mice administered riddelliine.
      In the 13-week studies, groups of 20 male and 20 female F344/N rats and B6C3FI
      mice were administered riddelliine in 0.1 M phosphate buffer by gavage five times
      per week for 13 weeks. Rats received 0, 0.1, 0.33, 1.0, 3.3, or 10 mg/kg and mice
      received 0, 0.33, 1.0, 3.3, 10, or 25 mg/kg. Ten animals from each dose group
      were killed after 13 weeks of treatment. The remaining 10 animals in each dose
      group were observed without further treatment for up to 14 weeks; five animals
      from each dose group were killed after 7 weeks of recovery, and the remaining
      five animals per dose group were killed at the end of the 14-week recovery
      period. During the 13-week treatment period, 19 of 20 male rats in the high-dose
      group died; all others survived. Body weight gains were decreased with increasing
      dose at Week 13. During the 14-week recovery period, all male rats survived, but
      five high-dose females died. Mean body weight gains of dosed and control male
      rats were similar throughout the 1 4-week recovery period; the final mean body
      weights of the treated males approached the final mean body weight of the
      controls. Similarly, mean body weight gains among the treated female rats were
      similar to the control value at the end of the 14- week recovery period. However,
      the final mean body weight of female rats given 1.0 or 3.3 mg/kg remained lower
      than that of controls at the end of the 14-week recovery period. In the 13-week
      study, the most significant treatment-related histopathologic lesions in rats
      occurred in the liver and included hepatocyte cytomegaly and karyomegaly,
      cytoplasmic vacuolization, centrilobular necrosis, mixed inflammatory cell
      infiltration, and bile duct hyperplasia. Vascular lesions in the kidneys and
      lungs were observed in most high- dose rats after 13 weeks of riddelliine
      administration. Additional lesions were found in the heart, spleen, kidneys, and
      pancreas at 13 weeks. At the end of the 14-week recovery period, hepatocyte
      karyomegaly, cytomegaly, and cytoplasmic vacuolization persisted. In addition,
      the incidence of bile duct hyperplasia was markedly increased in dosed female
      rats, and foci of cytologic alteration or hyperplastic hepatocytes were observed
      in dosed rats that were allowed to recover for up to 14 weeks. Adenomas of the
      liver occurred in 2 of 10 females in the 10 mg/kg group at 13 weeks and in one of
      five females in this group after the 14-week recovery period; no adenomas were
      found in the livers of control females. Serum activities of alkaline phosphatase
      in male rats and sorbitol dehydrogenase in female rats increased with increasing
      dose. Reticulocyte counts consistently increased and platelet counts consistently
      decreased with increasing dose in treated male and female rats. The clinical
      pathology findings were indicative of liver damage and erythrocyte and platelet
      sequestration. In mice in the 13-week study, no deaths related to riddelliine
      treatment occurred. Body weight gains were depressed at the two highest dose
      levels (10 and 25 mg/kg); the depression in body weight persisted throughout the
      14- week recovery period. Dose-related increases in erythrocyte counts in male
      mice and in reticulocyte counts in female mice were observed. Dose-related
      decreases in platelet counts were also observed in both males and females.
      Centrilobular cytomegaly in the liver was noted at 13 weeks in males and females
      administered 25 mg/kg riddelliine; this lesion persisted through the recovery
      period in females. At the end of the 14-week recovery period, bile duct
      hyperplasia was seen in the liver in high-dose female mice. Epithelial
      hyperplasia of the forestomach was noted in male and female mice in the 10 and 25
      mg/kg groups after 13 weeks of treatment, but this lesion became less severe
      during the recovery period. In male rats administered up to 3.3 mg/kg and in male
      mice administered up to 25 mg/kg for 13 weeks, riddelliine did not adversely
      affect any of the reproductive end points evaluated. In female rats given 10
      mg/kg and in female mice given 25 mg/kg, the length of the estrous cycle was
      increased. However, no unequivocal adverse effects were noted on fertility, pup
      growth and survival, or weight gain of dams during pregnancy during the mating
      trial in rats, although mean body weights of dams given 0.1 or 1.0 mg/kg were
      significantly lower than the mean body weight of the controls throughout
      gestation and lactation. In contrast, riddelliine administered at a dose of 25
      mg/kg was toxic to the dams in the mouse mating trial, resulting in lower body
      weights at the beginning of gestation and throughout lactation. Administration of
      25 mg/kg riddelliine to mouse dams also affected fetal growth and survival; the
      average live litter size was significantly reduced, the number of pups born dead
      was increased, and the average pup weight was reduced throughout the 21-day
      postpartum period. Riddelliine was mutagenic in Salmonella typhimurium strain
      TA100 with, but not without, S9 activation; results of mutagenicity testing were
      negative in strains TA97, TA98, and TA1535. Riddelliine induced sister chromatid
      exchanges in Chinese hamster ovary (CHO) cells with and without S9. Chromosomal
      aberrations were induced in CHO cells only in the presence of S9. The frequency
      of micronucleated erythrocytes in mouse peripheral blood samples was not elevated
      after 4 or 13 weeks of daily gavage treatments; however, a weakly positive
      response was noted in the peripheral blood and bone marrow of male mice
      administered a single, high dose of riddelliine by gavage. Unscheduled DNA
      synthesis was detected in cultured hepatocytes from male and female rats and mice
      following 5 or 30 days of riddelliine treatment by gavage. In addition, an
      increase in S-phase DNA synthesis was observed in cultured hepatocytes of male
      and female rats treated for either time period. In summary, the administration of
      riddelliine to rodents by gavage for up to 13 weeks resulted in a spectrum of
      neoplastic and nonneoplastic effects similar to those previously described for
      other pyrrolizidine alkaloids. Rats were found to be somewhat more sensitive than
      mice, and males more sensitive than females, to the toxic effects of riddelliine.
      The no-observed-adverse-effect level (NOAEL) for histopathologic changes in the
      13-week studies was 3.3 mg/kg body weight for mice and 0.1 mg/kg body weight for
      rats. The liver was the primary target of riddelliine-induced injury that
      resulted in lesions characterized by cytomegaly and cytologic alteration in rats
      and mice and also by marked necrotic and proliferative changes in rats.
      Riddelliine is carcinogenic to female F344/N rats, based on the occurrence of
      hepatocellular adenomas. Synonyms: 13,19-didehydro-12,18-dihydroxy senecionan
      11,16- dione; trans-15-ethylidine-12b-hydroxy-12a-hydroxymethyl-13-methylenesenec
      1-enine; 3-ethylidine-3,4,5,6,9,11,13,14,14a,14b-decahydro-6-hydroxy-6
      (hydroxymethyl)-5-methylene (1,6)di-oxacyclododecino(2,3,4-gh)-pyrrolizidine-2,7
      dione.

PMID- 12209180
TI  - NTP technical report on the toxicity studies of Ethylene Glycol Ethers: 2
      Methoxyethanol, 2-Ethoxyethanol, 2-Butoxyethanol (CAS Nos. 109-86-4, 110-80-5,
      111-76-2) Administered in Drinking Water to F344/N Rats and B6C3F1 Mice.
AB  - Glycol alkyl ethers represent a class of high-production-volume chemicals with
      widespread industrial applications as solvents and chemical intermediates.
      Comparative toxicity studies with three glycol ethers, 2-methoxyethanol, 2
      ethoxyethanol, and 2-butoxyethanol, were conducted in F344/N rats and B6C3F1 mice
      in both 2-week and 13-week drinking water studies. Toxicologic endpoints
      evaluated in animals included histopathology, hematology, clinical chemistry,
      urinalysis, and reproductive system parameters. Genetic toxicity was also
      evaluated for each glycol ether in several in vitro and in vivo assays. In the 2
      week studies, groups of five male and five female rats and mice received 2
      methoxyethanol, 2-ethoxyethanol, or 2-butoxyethanol in the drinking water.
      Estimates of compound consumption based on water consumption by male and female
      rats ranged from 100 to 400 mg/kg for 2-methoxyethanol, 200 to 1600 mg/kg for 2
      ethoxyethanol, and 70 to 300 mg/kg for 2-butoxyethanol. For mice, consumption
      values ranged from 200 to 1300 mg/kg for 2-methoxyethanol, 400 to 2800 mg/kg for
      2-ethoxyethanol, and 90 to 1400 mg/kg for 2-butoxyethanol. There were no chemical
      related effects on survival for rats or mice in the 2-week studies. Decreased
      body weight gains were noted for both male and female rats treated with 2
      methoxyethanol or 2-ethoxyethanol for 2 weeks, and there were dose-related
      decreases in water consumption for rats of each sex treated with the ethylene
      glycol ethers. Most of the changes in organ weights for rats and mice treated
      with the glycol ethers were sporadic (mice) or related to low final mean body
      weights (rats), except for thymic atrophy in male and female rats and testicular
      atrophy in males of both species receiving 2-methoxyethanol or 2-ethoxyethanol.
      In the 13-week studies in rats, groups of 10 males and 10 females received 2
      methoxyethanol, 2-ethoxyethanol, or 2-butoxyethanol in the drinking water at
      concentrations ranging from 750 to 6000 ppm, 1250 to 20,000 ppm, or 750 to 6000
      ppm, respectively. In the 13-week studies in mice, groups of 10 males and 10
      females received 2-methoxyethanol, 2-ethoxyethanol, or 2-butoxyethanol in the
      drinking water at concentrations ranging from 2000 to 10,000 ppm, 2500 to 40,000
      ppm, or 750 to 6000 ppm, respectively. Estimates of compound consumption based on
      water consumption by male and female rats ranged from 70 to 800 mg/kg for 2
      methoxyethanol, 100 to 2200- mg/kg for 2-ethoxyethanol, and 70 to 500 mg/kg for 2
      butoxyethanol. For-mice, consumption values ranged from 300 to 1800 mg/kg for 2
      methoxyethanol, 600 to 11,000 mg/kg for 2-ethoxyethanol, and 100 to 1300 mg/kg
      for 2-butoxyethanol. Chemical-related mortality occurred in male and female rats
      administered 4500 or 6000 ppm 2-methoxyethanol and in male and female rats
      administered 20,000 ppm 2-ethoxyethanol. No deaths occurred in rats administered
      2-butoxyethanol or in mice administered 2-methoxyethanol, 2-ethoxyethanol, or 2
      butoxyethanol. Decreased body weight gains occurred in dosed rats and mice in all
      three studies; the greatest reductions in body weight gain were seen with 2
      methoxyethanol. In rats administered 2-methoxyethanol or 2-ethoxyethanol,
      treatment-related histopathologic changes were observed in the testes, thymus,
      and hematopoietic tissues (spleen, bone marrow, and liver). A dose-related
      degeneration of the germinal epithelium in the seminiferous tubules of the testes
      was more severe in 2-methoxyethanol-treated rats than in rats treated with 2
      ethoxyethanol. In special stop-exposure studies in male rats in which
      administration of the glycol ethers was stopped after 60 days, marked
      degeneration of the seminiferous tubules was present in rats treated with 3000
      ppm 2-methoxyethanol, and mild to moderate degeneration was observed in rats
      treated with 1500 ppm. Moderate to marked testicular degeneration was present in
      rats treated with 10,000 or 20,000 ppm 2-ethoxyethanol but not in rats treated
      with 5000 ppm. After 30 and 56 days of recovery from treatment with these
      chemicals, only partial recovery from testicular degeneration was observed. There
      was no testicular degeneration after 60 days of treatment with 1500 to 6000 ppm 2
      butoxyethanol. 2-Methoxyethanol treatment for 13 weeks resulted in a progressive
      anemia associated with a cellular depletion of bone marrow and fibrosis of the
      splenic capsule. Anemia was also seen with 2-ethoxyethanol, but evidence of an
      adaptive response was indicated by increased hematopoiesis in the bone marrow,
      spleen, and liver. Toxicity with 2-butoxyethanol was limited to the liver and
      hematopoietic system. Cytoplasmic alteration and a minimal hepatocellular
      degeneration were present in the liver of male and female rats. A minimal anemia
      was present, and a hematopoietic response was evident in the bone marrow and
      spleen. In mice, 2-methoxyethanol and 2-ethoxyethanol had similar effects on the
      testes, spleen, and adrenal gland (females only). A dose-related degeneration of
      the germinal epithelium in seminiferous tubules of the testes was more severe
      with 2-methoxyethanol than with 2-ethoxyethanol. A dose-related increase in
      splenic hematopoiesis was also more prominent with 2-methoxyethanol. Both 2
      methoxyethanol and 2-ethoxyethanol caused a prominent lipid vacuolization of the
      X-zone of the adrenal gland in female mice. There were no chemical-related
      lesions attributed to 2-butoxyethanol administration in mice. All three of the
      glycol ethers were negative in Salmonella typhimurium mutation tests conducted
      with and without induced hamster and rat liver S9. In the mouse lymphoma L5178Y
      cell mutation assay, 2-ethoxyethanol was negative without S9 but was weakly
      positive in the presence of induced rat liver S9; 2-methoxyethanol and 2
      butoxyethanol were not tested in this assay. At high concentrations, 2
      ethoxyethanol induced sister chromatid exchanges (SCEs) in Chinese hamster ovary
      cells with and without S9. Chromosomal aberrations (Abs) were also induced by 2
      ethoxyethanol, but only in the absence of S9 and without a delay in cell cycle.
      In contrast, 2-butoxyethanol induced cell cycle delay but did not induce SCEs or
      Abs with or without S9. 2-Ethoxyethanol was the only glycol ether tested for
      induction of sex-linked recessive lethal mutations in germ cells of Drosophila
      melanogaster; both feeding and injection trials were negative. In summary, based
      on survival, decreased body weight gains, and histopathologic effects, the rank
      order of toxicity for the three glycol alkyl ethers was 2-methoxyethanol>2
      ethoxyethanol>2-butoxyethanol; the toxic effects were more severe in rats than in
      mice. In the 13-week study of 2-methoxyethanol in rats, a no-observed-adverse
      effect level (NOAEL) was not reached, since testicular degeneration in males and
      decreased thymus weights in males and females occurred at the lowest
      concentration administered (750 ppm). In the 13-week study of 2-ethoxyethanol in
      rats, the NOAEL for decreased thymus weights in males was 1250 ppm; for female
      rats treated with 2-ethoxyethanol for 13 weeks, the NOAEL for all histopathologic
      and hematologic effects was 5000 ppm. In rats treated with 2-butoxyethanol for 13
      weeks, the NOAEL for liver degeneration was 1500 ppm in males and females. For
      male mice treated with 2-methoxyethanol for 13 weeks, the NOAEL for testicular
      degeneration and increased hematopoiesis in the spleen was 2000 ppm. A NOAEL was
      not reached for female mice treated with 2-methoxyethanol, since adrenal gland
      hypertrophy and increased hematopoiesis in the spleen occurred at the lowest
      concentration administered (2000 ppm). For male mice treated with 2-ethoxyethanol
      for 13 weeks, the NOAEL for testicular degeneration and increased hematopoiesis
      in the spleen was 20,000 ppm. For female mice in the 13-week study of 2
      ethoxyethanol, the NOAEL for adrenal gland hypertrophy and increased
      hematopoiesis in the spleen was 5000 ppm. No clear chemical-related effects were
      seen in male or female mice administered 2-butoxyethanol for 13 weeks at
      concentrations as high as 6000 ppm. Synonyms: 2-Methoxyethanol: Ethylene glycol
      monomethyl ether; methyl cellosolve; 2-Ethoxyethanol: Ethylene glycol monoethyl
      ether; cellosolve; 2-Butoxyethanol: Ethylene glycol monobutyl ether; butyl
      cellosolve.

PMID- 12209181
TI  - NTP technical report on the toxicity studies of Glutaraldehyde (CAS No. 111-30-8)
      Adminstered by Inhalation to F344/N Rats and B6C3F1 Mice.
AB  - Glutaraldehyde is a potent sensory irritant with the capability to cross-link, or
      fix, proteins. It is used industrially as an antimicrobial agent and as a cold
      sterilant in hospitals, and it has a variety of other industrial uses. The
      toxicity of glutaraldehyde was evaluated in 2-week and 13-week inhalation
      exposure studies in F344/N rats and B6C3F1 mice. In addition to histopathology,
      evaluations included clinical pathology and assessments of sperm morphology and
      estrous cycle length. In vitro genetic toxicity studies included assessments of
      mutagenicity in Salmonella typhimurium and in mouse lymphoma L5178Y cells and
      analysis of chromosomal aberrations and sister chromatid exchanges in Chinese
      hamster ovary cells. The ability of glutaraldehyde to induce sex-linked recessive
      lethal mutations was also studied in vivo in Drosophila melanogaster. In 2-week
      inhalation studies, groups of five rats and five mice of each sex were exposed to
      glutaraldehyde by whole-body inhalation at concentrations of 0, 0.16, 0.5, 1.6,
      5, and 16 ppm for 6 hours per day, 5 days per week. All rats and mice exposed to
      5 or 16 ppm glutaraldehyde died before the end of the studies; all mice exposed
      to 1.6 ppm also died. Rats exposed to 1.6 ppm did not gain weight. Deaths were
      attributed to severe respiratory distress. Mice appeared to be more sensitive
      than rats because the small airways of the nasal passage of mice were more easily
      blocked by cell debris and keratin. Lesions noted in the nasal passage and larynx
      of rats and mice included necrosis, inflammation, and squamous metaplasia. At
      higher exposure concentrations, similar lesions were present in the trachea of
      rats and mice and in the lung and on the tongue of rats. In 13-week studies,
      groups of 10 rats and 10 mice of each sex were exposed to glutaraldehyde by whole
      body inhalation at concentrations of 0, 62.5, 125, 250, 500, and 1000 ppb for 6
      hours per day, 5 days per week. There were no exposure-related deaths in rats,
      but all mice exposed to 1000 ppb and two female mice exposed to 500 ppb died
      before the end of the study. Body weight gains were reduced in male rats exposed
      to 1000 ppb and in female rats exposed to 500 or 1000 ppb. Body weight gains of
      male mice exposed to 125, 250, or 500 ppb and female mice exposed to 250 or 500
      ppb were reduced in a concentration-related manner. There was no clear evidence
      of systemic toxicity in rats or mice by histopathologic or clinical pathology
      assessments; however, exposure-related lesions in the respiratory tract were
      observed, and resembled those noted in the 2-week studies. In rats, the most
      severe lesions occurred in the anterior portions of the nasal passages and
      involved both the respiratory and olfactory epithelium. Hyperplasia and squamous
      metaplasia were most commonly noted on the lateral wall of the nasal cavity and
      on the tips of the nasoturbinates. Lesions were most extensive in rats exposed to
      1000 ppb, but were also noted in the 250 and 500 ppb groups and in one male
      exposed to 125 ppb. In mice, histopathologic lesions in the respiratory tract
      were most severe in animals in the 1000 ppb group and consisted of minimal to
      mild squamous metaplasia of the laryngeal epithelium, suppurative inflammation in
      the anterior parts of the nasal cavity, and minimal squamous metaplasia on the
      tips of the nasoturbinates. Necrosis and inflammation were noted at lower
      concentrations, primarily in the anterior portion of the nasal passage. In
      genetic toxicity studies, glutaraldehyde was mutagenic with and without S9
      metabolic activation in Salmonella typhimurium strains TA100, TA102, and TA104.
      Glutaraldehyde was mutagenic in mouse L5178Y lymphoma cells in the absence of S9
      and induced sister chromatid exchanges in Chinese hamster ovary cells with and
      without S9. In one laboratory, chromosomal aberrations were induced in Chinese
      hamster ovary cells by glutaraldehyde in the absence of S9 only; no increase in
      chromosomal aberrations was observed with or without S9 in a second laboratory.
      Glutaraldehyde did not induce sex-linked recessive lethal mutations in germ cells
      of male Drosophila melanogaster treated as adults by feeding or injection or
      treated as larvae by feeding. In summary, exposure of rats and mice to
      glutaraldehyde by inhalation for up to 13 weeks resulted in a spectrum of
      necrotic, inflammatory, and regenerative lesions confined to the upper
      respiratory tract. Mice were somewhat more sensitive than rats because the small
      airways of the nasal passage in mice were more prone to blockage with cellular
      debris, bacteria, and keratin. The no-observed-adverse-effect level (NOAEL) was
      125 ppb for respiratory lesions in rats. An NOAEL was not reached for mice, as
      inflammation was found in the anterior nasal passage at concentrations as low as
      62.5 ppb. Synonyms: 1,5-Pentanedial; glutaral; glutaric dialdehyde; 1,3
      diformylpropane.

PMID- 12209182
TI  - NTP technical report on the toxicity studies of 1,6-Hexanediamine Dihydrochloride
      (CAS No. 6055-52-3) Administered by Drinking Water and Inhalation to F344/N Rats
      and B6C3F1 Mice.
AB  - 1,6-Hexanediamine (HDA) is an aliphatic amine that is produced in large volumes
      in the United States. HDA is widely used as a corrosion inhibitor in lubricants
      and as an intermediate in the industrial synthesis of paints, resins, inks, and
      textiles. Toxicity studies of the dihydrochloride salt of HDA (HDDC) were
      conducted in male and female Fischer 344/N rats and B6C3F1 mice by the drinking
      water (2-week studies only) and whole-body inhalation routes (2-week and 13-week
      studies). Animals were evaluated for histopathology, clinical chemistry,
      hematology, and reproductive toxicity. In addition, the genetic toxicity of HDA
      was assessed in Salmonella typhimurium and in Chinese hamster ovary cells in
      vitro; HDDC was evaluated in the mouse micronucleus assay in vivo. In the 2-week
      drinking water studies, groups of 5 rats of each sex received HDDC at doses of
      0.75 to 6.7 mg/mL, and groups of 5 mice of each sex received doses of 0.2 to 3.0
      mg/mL for 14 or 15 days. All animals survived to the end of the studies. No gross
      or microscopic pathologic changes and no clinical abnormalities related to HDDC
      consumption were seen in any dose group. The only statistically significant
      change was a slight decrease in absolute and/or relative liver weights of female
      rats in the 1.7, 5.0, and 6.7-mg/mL treatment groups, in male rats in the 3.0
      mg/mL treatment group, and in female mice in the 0.8 mg/mL treatment group.
      Because there was no significant toxicity in these studies, 13-week drinking
      water studies were not conducted. In the 2-week inhalation studies, 5 rats and 5
      mice of each sex were exposed to 0, 10, 30, 89, 267, or 800 mg HDDC/m(3) for 6
      hours per day for 12 days. In the highest exposure group (800 mg/m(3)), all male
      and female rats, all female mice, and 2 male mice died before the end of the
      studies. In the remaining groups, there was a dose-dependent depression in body
      weight gain in male and female mice, but not in rats. Clinical signs were
      primarily related to upper respiratory tract irritation and included dyspnea and
      nasal discharge in rats and mice. Absolute and relative liver weights were
      reduced in some male mice, but this did not occur in a dose- dependent manner. In
      rats, histopathologic lesions that were considered related to chemical exposure
      included inflammation and necrosis of laryngeal epithelium as well as focal
      inflammation and ulceration of the respiratory and olfactory nasal mucosa. In
      mice, focal areas of inflammation and necrosis were present in the respiratory
      mucosa of the larynx and trachea in the 2 highest exposure groups. Nasal lesions,
      including focal inflammation and ulceration, and degeneration and necrosis of the
      olfactory and respiratory epithelium were also seen in mice. In addition, mild
      testicular degeneration was present in 2 mice from the highest exposure group
      (800 mg/m(3)). In the 13-week inhalation studies, 10 rats and 10 mice of each sex
      were exposed to 0, 1.6, 5, 16, 50, or 160 mg HDDC/m(3) for 6 hours per day, 5
      days per week for 13 weeks. In addition special groups of 20 male and 40 female
      rats and mice (mating trial animals) at each exposure level were included to
      assess the effect of HDDC on reproduction. All rats and mice in the base-study
      groups survived to the end of the studies, and there were no exposure-related
      changes in body weight. In the mating trials, 3 female mice exposed to 16 mg/m(3)
      and 1 female and 1 male mouse exposed to 50 mg/m(3) died before scheduled
      termination. These deaths, however, were not considered to be chemical related.
      In male mice in the base study, liver weights were increased relative to controls
      in the 2-highest exposure groups. No exposure-related changes in absolute or
      relative organ weights and no exposure-related clinical signs or gross lesions
      were seen in either species. In female rats, a dose-related decrease in white
      blood cell count was observed. Chemical-related microscopic lesions in male and
      female rats and mice were limited to the upper respiratory tract (larynx and
      nasal passages) in the 2 highest exposure groups and were similar in both
      species. These lesions included minimal to mild focal erosion/ulceration,
      inflammation, and hyperplasia of the laryngeal epithelium as well as degeneration
      of the olfactory and respiratory nasal epithelium. HDDC caused no significant
      changes in sperm morphology or in the length of the estrous cycle of rats or
      mice. In mating trials, HDDC demonstrated no adverse effects on reproduction of
      rats. The only statistically significant changes in reproductive parameters of
      mice were a slight increase in gestation length in the 50 mg/m(3) and 160 mg/m(3)
      exposure groups and a decrease in mean pup weight on Day 21 in the highest
      exposure group. These changes were not considered to be biologically significant.
      1,6-Hexanediamine was not mutagenic in 4 strains of Salmonella typhimurium, and
      it did not induce sister chromatid exchanges or chromosomal aberrations in
      cultured Chinese hamster ovary cells. These in vitro tests were conducted with
      and without exogenous metabolic activation (S9). Negative results were also
      obtained in an in vivo test that measured the frequency of micronucleated
      erythrocytes in peripheral blood of male and female mice. In summary, the
      toxicity of HDDC to rats and mice resulted from irritant properties of the
      chemical and was consistent with the effects of other irritant chemicals
      administered by inhalation. This toxicity was limited to the nose and airways. In
      the 2-week inhalation studies, deaths occurred in both rats and mice at the
      highest exposure level (800 mg/m(3)). In the 13-week studies, the no-observed
      adverse-effect-level (NOAEL) for respiratory damage was 5 mg/m(3) for rats and
      mice. HDDC had no adverse effect on reproduction of either species and was not
      genotoxic. Synonyms: Hexamethylenediamine dihydrochloride; 1,6-diaminohexane
      dihydrochloride; 1,6-hexamethylenediamine dihydrochloride; 1,6- hexylenediamine
      dihydrochloride; 1,6-diamino-n-hexane dihydrochloride; HMDA; HDA; HDDC.

PMID- 12209183
TI  - NTP Technical report on the toxicity studies of ortho-, meta-, and para-
      Nitrotoluenes (CAS Nos. 88-72-2, 99-08-1, 99-99-0) Administered in Dosed Feed to
      F344/N Rats And B6C3F1 Mice.
AB  - Nitrotoluenes are high production volume chemicals used in the synthesis of
      agricultural and rubber chemicals and in various dyes. Because of differences in
      the metabolism of the 3 isomers and their capability to bind to DNA, comparative
      toxicity studies of o-, m-, or p-nitrotoluene were conducted in F344 rats and
      B6C3F1 mice. Animals were evaluated for histopathology, clinical pathology, and
      toxicity to the reproductive system. The nitrotoluenes were also studied in
      several in vitro and in vivo assays for genetic toxicity. In 14-day studies, o
      nitrotoluene, m-nitrotoluene, or p-nitrotoluene was administered in the feed to
      male and female rats and mice at concentrations ranging from 388 to 20000 ppm (5
      animals/chemical/species/sex/dose). There were no effects on survival or clinical
      signs of toxicity in these studies, although animals at the higher doses showed
      decreases in body weight gains relative to controls. In the 13-week studies, o-,
      m-, or p-nitrotoluene was given to male and female rats and mice (10
      animals/chemical/species/ sex/dose) in the feed at concentrations between 625 and
      10000 ppm. The estimated daily doses based on measures of feed consumption were
      40 to 900 mg nitrotoluene/kg body weight/day for rats and 100 to 2000 mg/kg/day
      for mice and were similar for each of the 3 isomers when compared for each
      dietary level/sex/species. There were no effects on survival in any of the
      studies, and clinical signs of toxicity were limited to decreases in feed
      consumption. Decreased body weight gains occurred in dosed rats and mice in all
      studies at the higher dose levels and were most pronounced in rats receiving o
      nitrotoluene. In rats, histopathologic analyses after 13 weeks of dosing showed
      toxicity to kidney, spleen, and testis in animals receiving any of the 3 isomers,
      and toxicity to the liver and mesothelium in male rats given o-nitrotoluene.
      Kidney toxicity observed in male rats was characterized by the presence of
      hyaline droplets in tubular epithelial cells, attributed to an increase in the
      level of alpha-2MU-globulin. Pigment, possibly lipofuscin, and karyomegaly in the
      p-nitrotoluene study were present in the renal tubular epithelium of dosed male
      and female rats. In the spleen of treated male and female rats, there was a mild
      increase in hematopoiesis, hemosiderin deposition, and/or congestion; this effect
      was most severe with the para-isomer, followed by the ortho- and then the meta
      isomer. Administration of o-, m-, or p-nitrotoluene impaired testicular function
      of the rat, shown by degeneration of the testis and reduction in sperm
      concentration, motility, and spermatid number. All 3 isomers increased the length
      of the estrous cycle in rats. Hepatic toxicity was characterized by cytoplasmic
      vacuolization and oval cell hyperplasia and by an increase in the level of serum
      bile acids, SDH, and ALT activities in male rats given o-nitrotoluene. There was
      no histopathologic evidence for liver toxicity in male or female rats with the m-
      or p-isomers, or in female rats with the o-isomer; but evidence of liver injury
      was observed in these groups, indicated by increases in relative liver weights
      and elevations in bile acids and liver enzymes in serum. Mesotheliomas of the
      tunica vaginalis were observed in 3/10 male rats receiving o-nitrotoluene at 5000
      ppm, and mesothelial cell hyperplasia was observed in 2/10 male rats receiving o
      nitrotoluene at 10000 ppm. The only histopathologic evidence for toxicity in mice
      in the 13- week studies occurred in the olfactory epithelium in mice receiving o
      nitrotoluene, where the chemical caused degeneration and metaplasia. No liver
      lesions were noted in mice, but the 3 isomers caused increases in relative liver
      weights. There was no toxicity to the reproductive system in male or female mice
      treated with any of the nitrotoluene isomers. The 3 nitrotoluene isomers were not
      mutagenic in Salmonella typhimurium strains TA100, TA1535, TA1537, and TA98. Only
      p-nitrotoluene induced chromosomal aberrations in cultured Chinese hamster ovary
      (CHO) cells, and this required metabolic activation. Sister-chromatid exchanges
      were increased in CHO cells following exposure to each isomer; the requirement
      for metabolic activation varied. Only p-nitrotoluene was studied in the mouse
      lymphoma L5178Y test; it caused mutations with metabolic activation. Unscheduled
      DNA synthesis (UDS) was increased in in vitro incubations of hepatocytes isolated
      from both sexes of rats and mice after receiving a single in vivo oral dose of o
      nitrotoluene. UDS was not increased in a similar study with male rats given m- or
      p-nitrotoluene. o-Nitrotoluene also induced s-phase DNA synthesis in hepatocytes
      of rats but not in those of mice. In summary, the 3 nitrotoluene isomers were
      toxic to the kidney, spleen and/or reproductive system in rats; o-nitrotoluene
      also caused lesions in the liver of male rats. No treatment-related lesions were
      noted in mice except with o-nitrotoluene where olfactory epithelium degeneration
      occurred. The increase in relative liver weights and the increase in UDS in liver
      indicate that all 3 isomers affected the liver of female rats and of male and
      female mice, even though histopathologic lesions were not observed. In general,
      the extent of the toxicity was most severe with the o-isomer in both rats and
      mice. o-Nitrotoluene was carcinogenic in male rats in 13-week studies, based on
      the occurrence of mesothelioma and mesothelial cell hyperplasia in dosed groups.
      Synonyms: o-NT, 2NT, 2-nitrotoluene, 2-methylnitrobenzene, 2-nitrotoluol; m-NT,
      3NT, 3-nitrotoluene, 3-methylnitrobenzene, 3-nitrotoluol; p-NT, 4NT, 4
      nitrotoluene, 4-methylnitrobenzene, 4-nitrotoluol. 

PMID- 12209184
TI  - NTP technical report on the toxicity studies of N,N-Dimethylformamide (CAS No. 68
      12-2) Administered by Inhalation to F344/N Rats and B6C3F1 Mice.
AB  - N,N-Dimethylformamide (DMF), a colorless liquid with a high boiling point, is a
      solvent used in a large number of industrial processes. Male and female F344/N
      rats (30/sex/group) and B6C3F1 mice (10/sex/group) were exposed to DMF vapors at
      concentrations of 0, 50, 100, 200, 400, or 800 ppm, 6 hours/day, 5 days/week, for
      13 weeks in whole body exposure inhalation studies. In addition to
      histopathology, sperm morphology, and vaginal cytology, which were evaluated in
      both species, the studies examined clinical pathology, cardiovascular, and renal
      function in rats only. In genetic toxicity studies, DMF was not mutagenic in
      Salmonella typhimurium strains TA100, TA1535, TA1537, or TA98, with or without S9
      activation, nor did it induce germ cell mutations in male Drosophila melanogaster
      treated by feeding or injection. No induction of sister chromatid exchanges or
      chromosomal aberrations was noted in cultured Chinese hamster ovary cells treated
      in vitro with DMF, with or without an S9 metabolic activation system. In one
      laboratory, a marginal increase in mutant colonies was observed after treatment
      of mouse lymphoma L5178Y/TK+/- cells with DMF in the absence of S9; results from
      studies in 2 other laboratories were negative. In the 13-week studies, all rats
      survived exposures to DMF. Body weight gains were reduced by 50-65% in rats
      exposed at 800 ppm and to a lesser extent in the 400 ppm group. Evidence of
      hepatocellular injury was noted as early as day 4, based on increases in
      activities of liver-specific enzymes in serum in rats of both sexes exposed at
      200-800 ppm. Serum cholesterol levels were increased at all exposure
      concentrations. Relative liver weights were increased in male rats exposed at 100
      ppm and higher concentrations, and in female rats at all concentrations. Minimal
      to moderate centrilobular hepatocellular necrosis was seen in rats of both sexes
      exposed at 400 and 800 ppm; the lesion was more severe in females. There were no
      clear, adverse effects seen in urinalyses, in electrocardiographic studies, or in
      male reproductive system evaluations that could be related to DMF exposure.
      Hematologic studies showed mild hemoconcentration in males and females. Prolonged
      diestrus was observed in females exposed at 800 ppm. Among mice exposed to DMF
      for 13 weeks, there was no chemically related mortality. Body weight gains were
      approximately 30% less than controls in females exposed at 800 ppm. Relative
      liver weights were increased in males and females at all exposure concentrations.
      Centrilobular hepatocellular hypertrophy (minimal to mild) was found in all
      groups of male mice exposed to DMF, and in female mice exposed at 100 ppm and
      higher concentrations. The length of the estrous cycle in mice increased with
      increasing DMF exposure. In summary, DMF-related effects were seen in the liver
      of both rats and mice, with rats being more severely affected. For rats of both
      sexes, the no-observed-adverse-effect level (NOAEL) was 200 ppm, based on the
      absence of liver histopathology, although liver function assays and liver weights
      showed changes at all exposure levels (as low as 50 ppm). For mice,
      hepatocellular hypertrophy or increased liver weights occurred at all exposure
      concentrations. Synonyms: DMF, DMFA.

PMID- 12209185
TI  - NTP technical report on the toxicity studies of 2-Hydroxy-4-methoxybenzophenone
      (CAS No. 131-57-7) Adminstered Topically and in Dosed Feed to F344/N Rats and
      B6C3F1 Mice.
AB  - 2-Hydroxy-4-methoxybenzophenone (HMB) occurs naturally in flower pigments and is
      synthesized for use in sunscreens, as a UV stabilizer in various cosmetic
      products, and in plastic surface coatings and polymers. Toxicity studies of HMB
      were performed in F344/N rats and B6C3F1 mice, by administering HMB in feed and
      by topical application, in studies of 2 weeks' (5 animals/sex, dose and species)
      and 13 weeks' (10 animals/sex, dose and species) duration. Assessments included
      hematology, clinical chemistry, urinalysis, reproductive toxicity, and
      histopathologic evaluations. In both 2- and 13-week dosed feed studies, rats
      received diets containing 0, 3125, 6250, 12500, 25000, or 50000 ppm HMB. One high
      dose female rat died during the 2-week study. Body weight gains of high-dose male
      and female rats were reduced in the 13-week study. Liver and kidney weights were
      increased in dosed rats in both studies. In the 2-week studies, enlarged livers
      were associated with a marked hepatocyte cytoplasmic vacuolization in rats
      receiving diets containing concentrations of 6250 ppm HMB or higher; renal
      lesions, consisting of dilated tubules and regeneration of tubular epithelial
      cells, were found primarily in high-dose rats. In the 13-week studies, kidney
      lesions progressed to include papillary degeneration, or necrosis, and
      inflammation, while the liver lesion appeared to regress; liver enzymes in serum
      remained elevated. Rats receiving a diet with 50000 ppm HMB showed markedly lower
      epididymal sperm density and an increase in the length of the estrous cycle at
      the end of the 13-week studies. In 2-week dermal studies, rats received topical
      applications of 1.25 to 20 mg of HMB in an acetone or lotion vehicle. The only
      effects noted were small and variable increases in liver and kidney weights,
      reaching statistical significance primarily in the higher dose groups. In 13-week
      studies, rats received topical doses from 12.5 to 200 mg/kg HMB in acetone.
      Kidney weights were elevated in dosed groups of female rats. No other findings
      were attributed to HMB treatment. In 2- and 13-week dosed feed studies, mice
      received feed containing 0, 3125, 6250, 12500, 25000, or 50000 ppm HMB. A dose-
      related increase in liver weight associated with hepatocyte cytoplasmic
      vacuolization was the only finding in mice in the 2- week studies. Decreased body
      weight gains were dose-related in mice in the 13-week studies; mild increases in
      liver weights were seen in dosed mice of both sexes. Kidney weights were
      increased variably in dosed females. Microscopic lesions were noted only in the
      kidneys of males receiving 50000 ppm HMB; these included eosinophilic protein
      casts in dilated renal tubules and a mild inflammation associated with the
      dilated tubules. Mice in the highest dose group exhibited a decrease in
      epididymal sperm density and an increase in length of the estrous cycle. In 2
      week dermal studies, mice received topical applications from 0.5 to 8 mg HMB in
      an acetone or lotion vehicle. The only effects noted were minimal, variable
      increases in liver and kidney weights, primarily in the higher dose groups. In 13
      week studies, mice received topical doses of 22.75 to 364 mg/kg in acetone.
      Kidney weights were increased variably in dosed male mice. Epididymal sperm
      density was decreased at all 3 dose levels evaluated (22.75, 91, and 200 mg/kg).
      The genetic toxicity of HMB also was evaluated in mutagenicity studies with
      Salmonella typhimurium, in cytogenetic studies with Chinese hamster ovary (CHO)
      cells, and by evaluation of micronucleated erythrocytes in peripheral blood
      smears from mice in the 13-week studies. HMB was weakly mutagenic in Salmonella
      with metabolic activation, and induced sister-chromatid exchanges and chromosomal
      aberrations in CHO cells in the presence of a metabolic activation system. There
      was no increase in the frequency of micronucleated erythrocytes in the blood of
      mice receiving HMB. In summary, HMB produced generally similar effects following
      topical and oral administration to rats and mice. Consistent findings included
      decreases in epididymal sperm density, lengthened estrous cycle, and increased
      liver and kidney weights. Mice in the dosed feed studies exhibited microscopic
      changes in the kidneys, comprising tubular dilatation with eosinophilic protein
      casts. Dilatation, tubular regeneration, papillary degeneration, and inflammation
      were noted in the kidneys of rats; and liver lesions consisting of an apparently
      reversible hepatocyte cytoplasmic vacuolization occurred in both rats and mice. A
      no-observed-adverse-effect level (NOAEL) for microscopic lesions was 6250 ppm HMB
      in the diet for rats and mice. A NOAEL was not reached for decreased epididymal
      sperm density in the 13- week dermal study in mice (<23 mg/kg/day). Synonyms:
      Oxybenzone; 4-Methoxy-2-hydroxy-benzophenone; Cyasorb UV; Uvinul M 40; (2-hydroxy
      4-methoxyphenyl)phenyl-methanone; NSC-7778; Spectra-sorb UV; Syntase 62; UF 3;
      USAF CY-9; NCI-C60957.

PMID- 12209186
TI  - NTP technical report on the toxicity studies of Diethanolamine (CAS No. 111-42-2)
      Administered Topically and in Drinking Water to F344/N Rats and B6C3F1 Mice.
AB  - Diethanolamine is a high-production chemical used in cosmetics, in cutting
      fluids, as a dispersing agent for agricultural chemicals, and as an absorbent for
      acidic gases. Toxicology studies of diethanolamine were conducted in F344/N rats
      and B6C3F1 mice of both sexes for 2 weeks (5/sex/species/dose) and 13 weeks
      (10/sex/species/dose) to characterize and compare the effects of oral and dermal
      exposure. In addition to histopathology, evaluations included clinical pathology,
      urinalyses, and sperm morphology or vaginal cytology. In vitro genetic toxicity
      studies included assessments of mutagenicity in Salmonella typhimurium and mouse
      lymphoma L5178Y cells, analysis of chromosomal aberrations and sister chromatid
      exchange in Chinese hamster ovary cells, and determination of micronuclei formed
      in mice during the 13-week dermal exposure study. Groups of rats and mice
      received drinking water containing diethanolamine at concentrations of up to
      10000 ppm during studies of 2 or 13 weeks duration. In the 2-week studies, rats
      and mice of both sexes received in the were 0, 630, 1250, 5000, and 10000 ppm
      diethanolamine in the drinking water. In the 13-week studies, rats received 0,
      320, 630, 1250, 2500, and 5000 ppm (males) or 0, 160, 320, 630, 1250, and 2500
      ppm (females) in drinking water; male and female mice received 0, 630, 1250,
      2500, 5000, and 10000 ppm. All female rats in the 2 highest dose groups and 2
      males in the 10000 ppm group in the 2-week study died before the end of the
      study. In the 13-week study, deaths of mice occurred in the 3 highest dose
      groups; 2 male rats in the top dose group also died. Surviving animals in the
      higher concentration groups in both studies exhibited depressed weight gains.
      Rats receiving diethanolamine developed a poorly regenerative, microcytic anemia
      in both studies. In the 2-week study, dosed male and female rats had increased
      kidney weights, renal tubular cell necrosis, and decreased renal function; rats
      in the 13-week study also showed increased incidences or severity of nephropathy,
      tubular necrosis, and mineralization. Degeneration of the seminiferous tubules of
      the testis was noted in dosed males in both the 2- and 13-week studies, and sperm
      motility and count were decreased in the 13-week study. Demyelination in the
      brain (medulla oblongata) and spinal cord was observed in male and female rats in
      the 13-week study. In mice, dose-dependent increases in liver weight were
      observed in males and females in the 2-week study; cytologic alteration and
      necrosis of individual hepatocytes were observed in the highest dose group. In
      the 13-week drinking water study in mice, nephropathy and tubular necrosis were
      observed in males, and degeneration of cardiac myocytes, and hepatocellular
      necrosis were seen in males and females. Cytologic alteration in the
      submandibular salivary gland was noted in male and female mice. Hepatocyte
      cytologic alteration also was noted in all dosed groups of mice. In the 2-week
      dermal studies, groups of rats and mice were administered daily doses of
      diethanolamine in 95% ethanol, ranging from 160 to 2500 mg/kg for mice, and from
      125 to 2000 mg/kg for rats, 5 days per week. In 13-week studies, dermal doses
      ranged from 32 to 500 mg/kg for rats, and from 80 to 1250 mg/kg for mice. In the
      2-week study, early deaths of male rats and male and female mice occurred in the
      highest dose groups and in female rats in the 2 highest dose groups (1000 and
      2000 mg/kg). Body weight gains were reduced in rats and mice in the higher dose
      groups. Early deaths in the 13-week study were observed in the highest dose
      groups of rats (500 mg/kg) and mice (1250 mg/kg). Body weight gains were reduced
      in rats and mice given the higher doses. Rats in the dermal studies exhibited
      dose-dependent hematologic and renal function changes similar to those observed
      in rats in the drinking water study. In addition, in the 2-week study, rats
      exhibited ulcerative skin lesions at the site of application, accompanied by
      inflammatory cell infiltration, hyperkeratosis, and acanthosis (hyperplasia) of
      the epidermis.dermis. Hyperkeratosis, without ulceration, was observed in some
      animals. Ulceration at the site of application was observed in male and female
      mice. Acanthosis, without ulceration or inflammatory cell infiltration, was
      observed in mice in all lower dose groups. In the 13-week study, skin lesions at
      the site of application included ulceration and inflammation, hyperkeratosis, and
      acanthosis. Liver weights were increased in male and female rats, but there were
      no associated histopathological changes. Other treatment-related effects observed
      in rats included demyelination in the brain and spinal cord, and nephropathy,
      renal tubular necrosis, and/or tubular mineralization; mice exhibited cytological
      alterations in the liver and/or hepatocellular necrosis, renal tubular epithelial
      necrosis, and cardiac myocyte degeneration. In in vitro genetic toxicity studies,
      diethanolamine was not mutagenic in Salmonella typhimurium or mouse L5178Y
      TK&plusmn; cells. Diethanolamine did not induce sister-chromatid exchanges or
      chromosomal aberrations in Chinese hamster ovary cells, nor did it induce
      micronuclei in peripheral blood erythrocytes in mice exposed by topical
      application for 13 weeks. All in vitro studies were conducted with and without S9
      activation. Target organs of diethanolamine toxicity identified in these studies
      included bone marrow, kidney, brain, spinal cord, testis, and skin in rats, and
      liver, kidney, heart, salivary gland, and skin in mice. A no-observed-adverse
      effect-level (NOAEL) was not achieved for hematological changes or nephropathy in
      rats (<160 ppm), or for cytologic alteration of the liver in mice (<630 ppm) in
      the drinking water studies. In the dermal studies, a NOAEL was not achieved for
      hematological changes, nephropathy, or hyperkeratosis of the skin in rats (<32
      mg/kg), or for cytologic alteration of the liver or acanthosis of the skin in
      mice (<80 mg/kg). Synonyms: 2,2&vprime;-iminodiethanol; 2,2&vprime;
      iminobisethanol; diethylolamine; bis(hydroxy-ethyl)amine;
      2,2'dihydroxydiethylamine; 2,2&vprime;-aminodiethanol.

PMID- 12209187
TI  - NTP technical report on the toxicity studies of Formic Acid (CAS No. 64-18-6)
      Administered by Inhalation to F344/N Rats and B6C3F1 Mice.
AB  - Formic acid occurs in a variety of plants and fruits, mammalian tissues, and
      insect venoms. It is used industrially in preparing a variety of drugs, dyes, and
      chemicals; as a decalcifier; and in leather tanning. Formic acid also is an
      environmental contaminant of air and water and has been identified as the toxic
      intermediate (formate) in methanol poisoning. Two- and 13-week toxicity studies
      of formic acid were conducted in male and female F344/N rats and B6C3F1 mice by
      whole body inhalation exposure to formic acid vapors. In addition, in vitro
      genetic toxicity studies were performed with Salmonella typhimurium, with or
      without metabolic activation. Formic acid was not mutagenic in this assay. In 2
      week studies, groups of 5 F344/N rats and 5 B6C3F1 mice of each sex were exposed
      to formic acid for 6 hours a day, 5 days a week, at concentrations of 0, 31,
      62.5, 125, 250, or 500 ppm. Deaths occurred in animals exposed to 500 ppm (rats
      and mice) and 250 ppm (1 female mouse). Microscopic lesions in the respiratory
      and olfactory epithelia occurred in rats and mice exposed to 62.5 ppm and higher
      concentrations, with the severity related to the exposure concentration. The
      lesions consisted of squamous metaplasia, necrosis, and inflammation. Exposures
      had minimal or no effects on coagulation times, blood pH and electrolytes, or on
      concentrations and activities of urine analytes in rats during the 2-week
      studies. In 13-week studies, groups of 10 animals of each species and sex were
      exposed to formic acid at concentrations of 0, 8, 16, 32, 64, and 128 ppm for 6
      hours a day, 5 days a week. Two mice, 1 male and 1 female, died in the 128 ppm
      groups. Body weight gains were significantly decreased in mice exposed to 64 and
      128 ppm formic acid. Microscopic changes in rats and mice ranged from minimal to
      mild in severity and generally were limited to animals in the 128 ppm groups.
      Lesions related to exposure to formic acid consisted of squamous metaplasia and
      degeneration of the respiratory and olfactory epithelia, respectively.
      Hematologic and serum biochemical changes at interim and terminal time points
      were minimal to mild and, generally, were consistent with hemoconcentration.
      Overall, the effects of formic acid were consistent with those of irritant
      chemicals administered by inhalation exposure. The no-observed-adverse-effect
      level (NOAEL) for respiratory injury was 32 ppm in rats and mice. There was no
      significant evidence of systemic toxicity in these studies. Synonyms: Aminic
      Acid, Formylic Acid, Methanoic Acid, Hydrogen Carboxylic Acid.

PMID- 12209188
TI  - NTP technical report on the toxicity studies of Pesticide/Fertilizer Mixtures
      Administered in Drinking Water to F344/N Rats and B6C3F1 Mice.
AB  - Toxicity studies were performed with pesticide and fertilizer mixtures
      representative of groundwater contamination found in California and Iowa. The
      California mixture was composed of aldicarb, atrazine, 1,2-dibromo-3
      chloropropane, 1,2- dichloropropane, ethylene dibromide, simazine, and ammonium
      nitrate. The Iowa mixture contained alachlor, atrazine, cyanazine, metolachlor,
      metribuzin, and ammonium nitrate. The mixtures were administered in drinking
      water (with 512 ppm propylene glycol) to F344/N rats and B6C3F1 mice of each sex
      at concentrations ranging from 0.1x to 100x, where 1x represented the median
      concentrations of the individual chemicals found in studies of groundwater
      contamination from normal agricultural activities. This report focuses primarily
      on 26-week toxicity studies describing histopathology, clinical pathology,
      neurobehavior/neuropathology, and reproductive system effects. The genetic
      toxicity of the mixtures was assessed by determining the frequency of micronuclei
      in peripheral blood of mice and evaluating micronuclei and sister chromatid
      exchanges in splenocytes from female mice and male rats. Additional studies with
      these mixtures that are briefly reviewed in this report include teratology
      studies with Sprague-Dawley rats and continuous breeding studies with CD-1 Swiss
      mice. In 26-week drinking water studies of the California and the Iowa mixtures,
      all rats (10 per sex and group) survived to the end of the studies, and there
      were no significant effects on body weight gains. Water consumption was not
      affected by the pesticide/fertilizer contaminants, and there were no clinical
      signs of toxicity or neurobehavioral effects as measured by a functional
      observational battery, motor activity evaluations, thermal sensitivity
      evaluations, and startle response. There were no clear adverse effects noted in
      clinical pathology (including serum cholinesterase activity), organ weight,
      reproductive system, or histopathologic evaluations, although absolute and
      relative liver weights were marginally increased with increasing exposure
      concentration in both male and female rats consuming the Iowa mixture. In 26-week
      drinking water studies in mice, one male receiving the California mixture at 100x
      died during the study, and one control female and one female in the 100x group in
      the Iowa mixture study also died early. It could not be determined if the death
      of either of the mice in the 100x groups was related to consumption of the
      pesticide/fertilizer mixtures. Water consumption and body weight gains were not
      affected in these studies, and no signs of toxicity were noted in clinical
      observations or in neurobehavioral assessments. No clear adverse effects were
      noted in clinical pathology, reproductive system, organ weight, or
      histopathologic evaluations of exposed mice. The pesticide/fertilizer mixtures,
      when tested over a concentration range similar to that used in the 26-week
      studies, were found to have no effects in teratology studies or in a continuous
      breeding assay examining reproductive and developmental toxicity. The California
      and Iowa pesticide mixtures were tested for induction of micronuclei in
      peripheral blood erythrocytes of female mice. Results of tests with the
      California mixture were negative. Significant increases in micronucleated
      normochromatic erythrocytes were seen at the two-highest concentrations (10x and
      100x) of the Iowa mixture, but the increases were within the normal range of
      micronuclei in historical control animals. Splenocytes of male rats and female
      mice exposed to these mixtures were examined for micronucleus and sister
      chromatid exchange frequencies. Sister chromatid exchange frequencies were
      marginally increased in rats and mice receiving the California mixture, but
      neither species exhibited increased frequencies of micronucleated splenocytes.
      None of these changes were considered to have biological importance. In summary,
      studies of potential toxicity associated with the consumption of mixtures of
      pesticides and a fertilizer representative of groundwater contamination in
      agriculturative of groundwater contamination in agricultural areas of Iowa and
      California failed to demonstrate any significant adverse effects in rats or mice
      receiving the mixtures in drinking water at concentrations as high as 100 times
      the median concentrations of the individual chemicals determined by groundwater
      surveys. NOTE: These studies were supported in part by funds from the
      Comprehensive Environmental Response, Compensation, and Liability Act trust fund
      (Superfund) by an interagency agreement with the Agency for Toxic Substances and
      Disease Registry, U.S. Public Health Service.

PMID- 12209189
TI  - NTP technical report on the toxicity studies of a Chemical Mixture of 25
      Groundwater Contaminants Administered in Drinking Water to F344/N Rats and
      B6C3F(1) Mice.
AB  - Toxicity studies were performed with a chemically defined mixture of 25
      groundwater contaminants, using dose levels considered to have environmental
      relevance. The mixture contained 19 organic compounds and six metals (shown
      below); the selection of these compounds was based primarily on the frequency of
      their occurrence in United States Environmental Protection Agency surveys of
      groundwater contamination in the vicinity of hazardous waste disposal sites. This
      report focuses primarily on 26-week drinking water toxicity studies with male and
      female F344/N rats and B6C3F(1) mice. The endpoints evaluated included
      histopathology, clinical pathology, neurobehavioral studies, and reproductive
      toxicity. Additional studies using this same chemical mixture are briefly
      reviewed in this report and include an evaluation of spermatogenesis in B6C3F(1)
      mice exposed to the chemical mixture for 13 weeks, a continuous breeding study
      with Sprague-Dawley rats and CD-1(R) Swiss mice, studies of myelotoxicity in
      B6C3F(1) mice exposed to the chemical mixture for up to 31.5 weeks, studies of
      immunosuppression in B6C3F(1) mice exposed for up to 13 weeks, in vitro
      mutagenicity assays in Salmonella typhimurium and Escherichia coli, and measures
      of genetic damage in bone marrow and peripheral blood of F344/N rats and B6C3F(1)
      mice in 2-week drinking water studies. In a 26-week drinking water study in which
      rats were administered the chemical mixture at composite contaminant
      concentrations of 0, 11, 38, 113, or 378 ppm, no deaths occurred and the body
      weight gain of high-dose males was slightly less than that of the controls. Water
      consumption decreased with dose and was 24% to 28% less than that of the controls
      at the highest concentration. Changes in organ weights occurred primarily in high
      dose rats and included increased absolute and relative liver and kidney weights
      in females, increased relative kidney weight in males, and decreased absolute and
      relative thymus weights in males and females. Hematologic assessments indicated
      that rats receiving 378 ppm developed a microcytic anemia consistent with that
      accompanying iron depletion. Multiple foci of inflammation occurred in the liver
      of exposed rats. In high-dose females, these liver lesions were especially
      prominent and included bile duct and oval cell hyperplasia. Inflammation also
      occurred in the mesenteric lymph nodes, the adrenal gland, and the spleen. The
      amount of hemosiderin in the spleens of rats receiving the higher concentrations
      of the chemical mixture was less than normal. Components of a chemical mixture of
      25 groundwater contaminants include acetone, aroclor 1260, arsenic, benzene,
      cadmium, carbon tetrachloride, chlorobenzene, chloroform, chromium, 1,1
      dichloroethane, 1,2-dichloroethane, 1,1-dichloroethylene, 1,2-trans
      dichloroethylene, di(2-ethylhexyl) phthalate, ethylbenzene, lead, mercury,
      methylene chloride, nickel, phenol, tetrachloroethylene, toluene, 1,1,1
      trichloroethane, trichloroethylene, xylenes. In a 26-week study in which mice
      were exposed to the chemical mixture at concentrations of 0, 11, 38, 113, and 378
      ppm in drinking water, there were no clear adverse effects noted in survival,
      weight gain, clinical pathology parameters, or histopathologic evaluations. Water
      consumption decreased with increasing dose, and water consumption by high-dose
      mice was approximately 40% less than that by the controls. In neurobehavioral
      assessments, no clear treatment-related effects were observed in measures of
      forelimb and hindlimb grip strength, hindlimb footsplay, motor activity, response
      to a thermal stimulus, or startle response in rats or mice evaluated at 6-week
      intervals throughout the 26- week drinking water studies. There were no effects
      on sperm morphology or motility or on estrous cycle length in rats or mice
      receiving the chemical mixture during the 26-week studies. Sperm concentration
      was decreased in F(1) CD-1(R) Swiss mice during continuous breeding studies,
      although there were no clear adverse effects on the fertility of Sprague-Dawley
      rats or CD-1(R) Swiss mice in th CD-1&reg; Swiss mice in these studies. Pup
      weight, the number of live males, and the number of male pups per litter were
      slightly decreased in dosed rats in the continuous breeding study in rats; the
      number of live female mouse pups in litters born of the F(0) and F(1) generations
      was decreased in the 378 ppm group. The significance of these observations, if
      any, is not known. F(1) mice receiving 378 ppm had increased incidences of
      hepatic inflammation compared to the controls. In female B6C3F(1) mice that
      received the chemical mixture in drinking water at concentrations as high as 756
      ppm for 2 weeks or 378 ppm for 13 weeks, assessments of immune function showed
      suppression of hematopoietic stem cells and antigen-induced antibody-forming
      cells. This was manifested by impaired resistance to challenge with a nonlethal
      strain of mouse malaria, Plasmodium yoelii. Additional evidence of an adverse
      effect on hematopoietic stem cells was demonstrated by decreases in the in vitro
      colony-forming ability of granulocyte-macrophage progenitor cells and erythroid
      precursor cells isolated from female mice that had received the chemical mixture
      at a concentration of 378 or 756 ppm in 31.5 week studies. Potential genotoxic
      effects of the chemical mixture to the bone marrow of F344/N rats and B6C3F(1)
      mice were assessed in 2-week drinking water studies with concentrations as high
      as 756 ppm. Small increases in sister chromatid exchanges and micronucleated
      polychromatic erythrocytes occurred in the bone marrow of dosed male mice, and
      micronucleated polychromatic erythrocytes were also increased in dosed female
      mice. The chemical mixture did not induce mutations in Salmonella typhimurium
      strains TA98 and TA100 and did not induce DNA damage in Escherichia coli with or
      without metabolic activation. In summary, rats receiving drinking water
      containing a mixture of 25 common groundwater contaminants at levels of potential
      environmental relevance developed inflammatory lesions in the liver, spleen,
      lymph nodes, and adrenal gland, as well as evidence of an iron deficiency anemia.
      The inflammatory lesions could not be predicted based on the known toxic effects
      of the individual components of the chemical mixture. Mice exposed to similar
      concentrations of the chemical mixture did not show adverse effects in a standard
      toxicity study but developed deficits in bone marrow function, evidence of
      genetic damage, hepatic inflammation, and immunosuppression in other studies that
      generally included exposures to higher concentrations or exposures of longer
      duration. A no-observed-adverse-effect level for histologic injury (granulomatous
      inflammation of the liver) was 11 ppm in rats; however, no clear evidence for
      histologic injury was seen in mice exposed to concentrations of the chemical
      mixture as high as 378 ppm in a standard 26-week study. NOTE: These studies were
      supported in part by funds from the Comprehensive Environmental Response,
      Compensation, and Liability Act trust fund (Superfund) by an interagency
      agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public
      Health Service.

PMID- 12209190
TI  - NTP technical report on the toxicity studies of 1-Nitropyrene (CAS No. 5522-43-0)
      Administered by Inhalation to F344/N Rats.
AB  - 1-Nitropyrene is a by-product of combustion. It is the predominant nitrated
      polycyclic aromatic hydrocarbon emitted in diesel engine exhaust and has been
      found at concentrations of up to 57 pg/m(3) in the air over urban and suburban
      areas. 1-Nitropyrene is detoxified mainly to 1-aminopyrene by nitro reduction. 1
      Nitropyrene can also undergo ring oxidation, depending on the concentration of
      oxygen. Aryl nitrenium ions generated by nitro reduction or K-region nitropyrene
      epoxides generated by ring oxidation can react with DNA, forming adducts. 1
      Nitropyrene was nominated for toxicity study because it is mutagenic, it is found
      in the environment, and it has potential for human exposure. Administration by
      inhalation was chosen because humans are exposed to 1-nitropyrene mainly by
      inhalation. Nose-only inhalation was chosen because whole-body inhalation
      exposure would require a large quantity of purified 1-nitropyrene that is
      expensive and difficult to procure. The study was performed in rats because of
      technical problems with conducting nose-only inhalation studies in mice and
      because mice are known to be more resistant to 1-nitropyrene toxicity. In the
      base study, groups of 10 male and 10 female 7-week-old F344/N rats were exposed
      to 0, 0.5, 2, 8, 20, or 50 mg/m(3) 1-nitropyrene aerosol, 6 hours per day, 5 days
      per week, for 13 weeks. At 13 weeks, rats were evaluated for histopathology,
      clinical pathology, and reproductive system effects. In a supplemental
      evaluation, toxicokinetic effects were assessed in male F344/N rats exposed to 1
      nitropyrene for 13 weeks. All rats survived to the end of the 13-week exposure.
      For all groups, body weight gains of exposed rats were similar to those of
      concurrent controls (but lower than those of historical whole body inhalation
      study control rats); however, liver weights of exposed male rats were higher than
      those of the controls. There were slight variations in certain hematology and
      clinical chemistry parameters for some groups, but these were not considered
      related to 1-nitropyrene exposure. Squamous metaplasia of the respiratory mucosa
      was observed in the larynx of male rats exposed to 1-nitropyrene at a
      concentration of 2 mg/m(3) or greater and of female rats at all exposure
      concentrations. Squamous metaplasia of the bronchial epithelium also occurred in
      male and female rats in the higher exposure groups. Cytoplasmic alteration of the
      nasal respiratory epithelium was observed in both sexes exposed to 1-nitropyrene
      at a concentration of 8 mg/m(3)or greater. No treatment-related effects on sperm
      motility or vaginal cytology were noted. However, testicular atrophy was observed
      in all male rats and was considered a secondary effect resulting from the daily
      confinement within the exposure tubes. The elimination half-life of 1-nitropyrene
      in the lungs was about 1 hour for rats exposed to 8 mg/m(3)and 6 hours for rats
      exposed to 50 mg/m(3). Lung burdens of 1-nitropyrene in rats exposed to 8 mg/m(3)
      remained the same for the 13-week duration; however, lung burdens in rats exposed
      to 50 mg/m(3) increased with time indicating that the rats were unable to clear
      the 1-nitropyrene between exposures. The half-life of 1-nitropyrene in the plasma
      of rats exposed to 50 mg/m(3) was about 1 hour. Based on data contained in this
      report and previously published reports on the genetic toxicity, carcinogenicity,
      and toxicokinetics of 1-nitropyrene, it is the opinion of the National Toxicology
      Program (NTP) that 1-nitropyrene has a high likelihood of being carcinogenic to
      the respiratory tract, particularly under exposure conditions that lead to
      significant accumulations of 1-nitropyrene in the lungs, and perhaps other organs
      of F344/N rats. In summary, nose-only inhalation exposure to 1-nitropyrene for 13
      weeks induced squamous metaplasia of the laryngeal and bronchial respiratory
      epithelium in male and female rats. Cytoplasmic alteration in the nasal
      respiratory epithelium were also induced in male and female rats. The no-observed
      adverse-effect level (NOAEL) for male rats was 0.5 mg/m(3). A NOAEL for female
      rats could not be determined from these studies. Synonyms: 3-Nitropyrene; Pyrene,
      1-nitro.

PMID- 12209191
TI  - NTP technical report on the toxicity studies of 2-Chloronitrobenzene (CAS No. 88
      73-3) and 4-Chloronitrobenzene (CAS No. 100-00-5) Administered by Inhalation to
      F344/N Rats and B6C3F1 Mice.
AB  - 2-Chloronitrobenzene and 4-chloronitrobenzene are oily yellow solids that are
      used primarily as chemical intermediates in the production of dyes, lumber
      preservatives, drugs, and photographic chemicals. Although these chemicals are
      solids at room temperature, the vapor pressures of these chemicals are
      sufficiently high to result in significant inhalation exposure. Toxicity studies
      of 2-chloronitrobenzene and 4-chloronitrobenzene were performed by exposing male
      and female F344/N rats and B6C3F1 mice to the chemicals by whole-body inhalation
      6 hours per day, 5 days per week, for 2 weeks or 13 weeks. Animals were evaluated
      for histopathology, clinical chemistry (rats), hematology (rats), and
      reproductive system effects. In separate studies, the dermal absorption of the
      chemicals was compared, and the absorption, distribution, metabolism, and
      excretion were partially characterized following oral administration to male
      F344/N rats. 2-Chloronitrobenzene and 4-chloronitrobenzene were also administered
      orally to CD-1(R) Swiss mice for evaluation of reproductive and developmental
      toxicity. Genetic effects were evaluated in Salmonella typhimurium, in Chinese
      hamster ovary cells, and in Drosophila melanogaster. The highest exposure
      concentrations used in the 2 week and 13 week studies were limited by technical
      factors in vapor generation to 18 ppm (115.2 mg/m(3)) for 2-chloronitrobenzene
      and 24 ppm (153.6 mg/m(3)) for 4-chloronitrobenzene. Other concentrations were 0,
      1.1, 2.3, 4.5, and 9 ppm (0, 7, 14.7, 28.8, and 57.6 mg/m(3)) for 2
      chloronitrobenzene and 0, 1.5, 3, 6, and 12 ppm (0, 9.6, 19.2, 38.4, and 76.8
      mg/m(3)) for 4-chloronitrobenzene. In 2-week studies with 2-chloronitrobenzene,
      all rats survived to the end of the study. One of five male mice exposed to 18
      ppm died, but weight gains of exposed rats and mice were not affected. Exposed
      rats and mice had concentration-related increases in liver weights, and spleen
      weights were increased in rats and mice exposed to 18 ppm. Histopathologic
      findings in rats were limited to hemosiderin deposition in the liver and spleen
      at the highest exposure concentration. Exposed mice, primarily those in the 18
      ppm groups, had coagulative necrosis, hepatocytomegaly, and granulomatous
      inflammation in the liver. Splenic changes including increased hematopoietic cell
      proliferation and hemosiderin deposition occurred at concentrations as low as 4.5
      ppm. In 13-week studies with 2-chloronitrobenzene, all rats survived to the end
      of the study; 2 of 10 male mice exposed to 18 ppm died. Body weight gains of
      exposed rats and mice were similar to or somewhat higher than those of the
      respective controls. Methemoglobinemia occurred in rats and resulted in a
      normocytic, normochromic anemia that became responsive by the end of the study.
      Exposed rats and mice had increased liver weights, but these increases were not
      as great as those seen in the 2-week studies. Spleen weights were increased in
      exposed rats. Histopathologic changes in rats included increased basophilia of
      centrilobular hepatocytes, pigmentation and regeneration of the proximal
      convoluted tubules of the kidney, and hyperplasia of the nasal cavity respiratory
      epithelium. In mice, hepatocellular necrosis, cytomegaly, mineralization, and
      chronic inflammation occurred in the liver, primarily in mice in the 18 ppm
      group, and hematopoietic activity in the spleen was increased. In 2-week studies
      with 4-chloronitrobenzene, all rats and mice survived to the end of the studies.
      Body weight gains of exposed rats were similar to those of the controls; body
      weight gains of exposed mice were greater than those of the controls. Liver and
      spleen weights were increased in exposed rats and mice. In rats, histopathologic
      changes in the liver were limited to an increase in hemosiderin pigment in
      Kupffer cells. The spleens of exposed rats were congested and had increased
      hematopoietic activity and hemosiderin deposition. Kidneys of exposed male rats
      had lesions consistent with hyaline droplet nephropathy. The proximal convoluted
      tubules of exposed female rats c contained hemosiderin. Microscopic changes in
      exposed mice primarily involved increased hematopoietic activity in the spleen
      and hemosiderin pigmentation in the spleen, liver, and proximal convoluted
      tubules in the kidney. In 13-week studies with 4-chloronitrobenzene, there were
      no deaths that were clearly related to exposure to 4-chloronitrobenzene. Body
      weight gains of exposed rats and mice were either equal to or greater than those
      of the controls. A more severe methemoglobinemia developed in rats exposed to 4
      chloronitrobenzene than occurred in rats exposed to 2-chloronitrobenzene, and
      this methemoglobinemia resulted in a responsive macrocytic, hyperchromic anemia.
      Spleen weights were markedly greater in exposed rats and mice than in controls.
      In exposed rats, lesions in the spleen, liver, and kidney were similar to those
      described for the 2-week study. Additionally, increased hematopoietic cell
      proliferation in bone marrow, histiocytic hyperplasia in mediastinal lymph nodes,
      testicular atrophy, and chronic inflammation of the harderian gland occurred in
      exposed rats. In exposed mice, microscopic changes in the spleen and liver were
      similar to those noted in the 2-week study. Additional lesions included increased
      hematopoiesis and hemosiderin deposition in the bone marrow of exposed males and
      females and squamous cell hyperplasia of the forestomach epithelium in female
      mice. In reproductive system assessments, there was evidence of decreased
      spermatogenesis in rats exposed to either 2- or 4-chloronitrobenzene. In mice,
      effects were limited to a decrease in sperm motility in males exposed to 2
      chloronitrobenzene and an increase in estrous cycle length in females exposed to
      4-chloronitrobenzene. In continuous breeding studies, a progressive decrease in
      fertility was noted in CD-1&reg; Swiss mice receiving 4-chloronitrobenzene by
      oral gavage; fertility was not affected in mice administered 2-chloronitrobenzene
      by oral gavage. Percutaneous absorption of [14C]-2-chloronitrobenzene and [14C]-4
      chloronitrobenzene was demonstrated in rats. For doses ranging from 0.65 to 65
      mg/kg of either chemical, 33&percnt; to 40&percnt; of 2-chloronitrobenzene and
      51&percnt; to 62&percnt; of 4-chloronitrobenzene were absorbed under nonocclusive
      conditions. Oral absorption was somewhat higher than dermal absorption for both
      chemicals, and metabolism was complicated, with over 20 unidentified metabolites
      isolated from urine of rats given either 2- or 4-chloronitrobenzene. 2
      Chloronitrobenzene and 4-chloronitrobenzene were mutagenic in Salmonella
      typhimurium with S9 activation. In addition, both compounds induced sister
      chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells;
      requirements for S9 activation varied among testing laboratories. Neither
      compound induced sex-linked recessive lethal mutations in germ cells of male
      Drosophila melanogaster treated as adults or as larvae. In summary, inhalation
      exposure of rats and mice to 2- or 4-chloronitrobenzene resulted in methemoglobin
      formation and oxidative damage to red blood cells, leading to a regenerative
      anemia and a recognized spectrum of tissue damage and changes secondary to
      erythrocyte injury. In addition, numerous other lesions that were considered
      primary toxic effects occurred following exposure. These included renal hyaline
      droplet accumulation and testicular atrophy in male rats exposed to 4
      chloronitrobenzene and hyperplasia of the respiratory epithelium in rats exposed
      to 2-chloronitrobenzene. A no-observed-adverse-effect-level (NOAEL) for rats was
      not achieved, as increases in methemoglobin and histopathologic changes occurred
      at exposure concentrations as low as 1.1 ppm for 2-chloronitrobenzene and 1.5 ppm
      for 4-chloronitrobenzene in the 13-week studies. The NOAEL for histopathologic
      injury in mice was 4.5 ppm for 2-chloronitrobenzene and 6 ppm for 4
      chloronitrobenzene. 2-Chloronitrobenzene Synonyms: o-Cloronitrobenzene; 2-chloro
      1-nitrobenzene; ONCB. 4-chloronitrobenzene Synonyms: p-Chloronitrobenzene; 4
      chloro-1-nitrobenzene; PNCB.

PMID- 12209192
TI  - NTP technical report on the toxicity studies of Methylene Bis(thiocyanate) (CAS
      No. 6317-18-6) Administered by Gavage to F344/N Rats and B6C3F1 Mice.
AB  - Methylene bis(thiocyanate) is used as a biocide in a number of applications. Its
      major use is in water cooling systems and paper mills as an inhibitor of algae,
      fungi, and bacteria. Methylene bis(thiocyanate) was selected for study because of
      the potential for human exposure to the compound and because of the interest in
      organothiocyanates as a chemical class. Toxicity studies of methylene
      bis(thiocyanate) (approximately 98% pure) were conducted with male and female
      F344/N rats and B6C3F1 mice; the compound was administered to the animals by
      gavage in an aqueous methyl cellulose vehicle for 2 weeks or 13 weeks. In
      addition to these studies, the genetic toxicity of methylene bis(thiocyanate) was
      evaluated by determining mutagenicity in Salmonella typhimurium with and without
      S9 activation and frequency of micronucleated normochromatic erythrocytes in the
      peripheral blood of mice. In the 2-week studies, groups of five rats and five
      mice per sex were administered methylene bis(thiocyanate) at concentrations of 0,
      10, 20, 40, 80, and 160 mg/kg body weight. All animals in the two highest dose
      groups (80 and 160 mg/kg) died by Day 2 of the studies. Except for one female
      rat, all animals receiving 40 mg/kg methylene bis(thiocyanate) also died before
      the end of the studies. Few significant gross lesions were observed in the 80 and
      160 mg/kg groups. Clinical observations were similar to those reported for
      cyanide toxicity and included dyspnea, tremors. and ataxia. The stomach, which
      was identified as the target organ in rats and mice surviving for at least 24
      hours, had necrotic inflammatory lesions of the mucosal surface of both the
      glandular and nonglandular portions. In the 13-week studies, groups of 10 rats
      and 10 mice per sex were administered methylene bis(thiocyanate) at
      concentrations of 0, 1, 2, 4, 8, and 16 mg/kg body weight. In the rat study,
      deaths occurred in the 2, 4, 8, and 16 mg/kg groups, while in the mouse study,
      deaths occurred only in the 8 and 16 mg/kg groups. As in the 2-week studies, the
      stomach was identified as the primary target organ. However, the lower doses
      administered in the 13-week studies resulted in gastric effects that were limited
      to the forestomach and consisted primarily of squamous mucosal hyperplasia and
      hyperkeratosis. Rats receiving the higher doses of methylene bis(thiocyanate)
      developed a mild anemia, and sperm motility was decreased in male rats receiving
      4 or 8 mg/kg. Methylene bis(thiocyanate) was not mutagenic in S. typhimurium,
      with or without S9 activation. The frequencies of micronucleated normochromatic
      erythrocytes in the peripheral blood of dosed and control mice were similar.
      Chemical disposition studies of [14C]-labeled methylene bis(thiocyanate) were
      conducted in male F344 rats. In these studies, more than 90% of the administered
      radioactivity was eliminated in 48 hours. However, as the dose was increased from
      0.2 to 1 to 10 mg/kg, greater percentages of the administered radioactivity
      remained in the tissues. Blood cyanide concentrations were increased shortly
      after the administration of 10 mg/kg [14C]-methylene bis(thiocyanate) but were
      similar to control values 2 hours after dosing. Overall, the toxic effects of
      methylene bis(thiocyanate) were consistent with those of an irritant chemical
      administered by gavage. There was also some indication that the release of
      cyanide may result in acute toxicity at the higher dose levels used in these
      studies. The no-observed-adverse-effect level for forestomach lesions in the 13
      week studies was 4 mg/kg for male rats and 2 mg/kg for female rats and male and
      female mice. Synonyms: MBT; methylene-bis-thiocyanate; methylene bisthiocyanate;
      methylene dithiocyanate.

PMID- 12209193
TI  - NTP technical report on the toxicity studies of Isoprene (CAS No. 78-79-5)
      Administered by Inhalation to F344/N Rats and B6C3F1 Mice.
AB  - Isoprene, the 2-methyl analogue of 1,3-butadiene, has a high production volume
      and is used largely in the manufacture of synthetic rubber. Isoprene is also the
      major endogenous hydrocarbon exhaled in human breath. Two-week and 13-week
      inhalation toxicology studies were conducted in male and female F344/N rats and
      B6C3F1 mice to characterize potential adverse effects of isoprene. Male rats and
      male mice were also exposed to isoprene vapors for 6 months followed by a 6-month
      recovery period (stop- exposure protocol) to determine if isoprene produces a
      carcinogenic response similar to that of 1,3-butadiene after intermediate
      exposure durations. In addition to histopathology, evaluations included clinical
      pathology, tissue glutathione analyses, forelimb and hindlimb grip strength
      analyses, and sperm motility and vaginal cytology. Data from inhalation
      teratology studies of isoprene in rats and mice are also reported. In vitro
      genetic toxicity studies included assessments of mutagenicity in Salmonella
      typhimurium and sister chromatid exchanges and chromosomal aberrations in Chinese
      hamster ovary cells. In conjunction with the inhalation studies in mice,
      evaluations were also made of sister chromatid exchanges and chromosomal
      aberrations in bone marrow cells and micronuclei in peripheral blood of male mice
      exposed to isoprene for 12 days or 13 weeks. Target concentrations of isoprene in
      the inhalation chambers were 0, 438, 875, 1,750, 3,500, and 7,000 ppm in the 2
      week studies; 0, 70, 220, 700, 2,200, and 7,000 ppm in the 13-week and stop
      exposure studies; and 0, 280, 1,400, and 7,000 ppm in the teratology studies. In
      the 2-week studies, no changes related to chemical administration were observed
      in survival, body weight gain, clinical signs, hematologic or clinical chemistry
      parameters, or the incidence of gross or microscopic lesions in rats. In mice,
      there were no effects on survival; the mean body weight of males in the 7,000 ppm
      group was less than that of the controls. In mice, exposure to isoprene caused
      decreases in hematocrit values, hemoglobin concentrations, and erythrocyte
      counts, atrophy of the testis and thymus, cytoplasmic vacuolization of the liver,
      olfactory epithelial degeneration in the nasal cavity, and epithelial hyperplasia
      in the forestomach. Exposure to isoprene for 13 weeks produced no discernible
      toxicologic effects in rats. In the stop-exposure study, interstitial cell
      hyperplasia of the testis was observed in all male rats in the 7,000 ppm group
      after 6 months of exposure. Following the 6-month recovery period, male rats
      exposed to 700, 2,200, or 7,000 ppm isoprene had slightly greater incidences of
      interstitial cell adenomas of the testes than the controls. Exposure to isoprene
      for 13 weeks or 6 months produced no clear exposure-related effects on body
      weight gain in male or female mice; however, survival was decreased for male mice
      exposed to 7,000 ppm isoprene for 6 months. More notably, toxic and carcinogenic
      effects were induced at multiple organ sites in mice exposed to isoprene. After 6
      months of exposure and 6 months of recovery, male mice exposed to 700 ppm or
      higher concentrations of isoprene had greater incidences of neoplasms of the
      liver (0 ppm, 7/30; 70 ppm, 3/30; 220 ppm, 7/29; 700 ppm, 15/30; 2,200 ppm,
      18/30; 7,000 ppm, 17/28), lungs (2/30, 2/30, 1/29, 5/30, 10/30, 9/28),
      forestomach (0/30, 0/30, 0/30, 1/30, 4/30, 6/30), and harderian gland (2/30,
      6/30, 4/30, 14/30, 13/30, 12/30) than the controls. In addition to the higher
      neoplasm incidences in male mice exposed to 700 ppm or greater, incidences of
      multiple neoplasms and/or neoplasms of greater malignancy were also higher than
      in the controls. Hematologic effects similar to those occurring in exposed mice
      in the 2-week study, plus greater mean cell volume values than in the controls,
      were observed after 24 days and after 13 weeks of exposure to isoprene. These
      hematologic effects, which were not accompanied by greater reticulocyte counts or
      a higher frequency of polychromatic erythrocytes than controls, were indicative
      of a nonresponsive, macrocytic anemia. In male mice in the stop-exposure study,
      partial hindlimb paralysis in the 7,000 ppm group and a dose-related decrease in
      grip strength were observed near the end of the 6-month exposure period. Other
      nonneoplastic effects in mice exposed to isoprene included spinal cord and
      sciatic nerve degeneration, skeletal muscle atrophy, degeneration of the
      olfactory epithelium, epithelial hyperplasia of the forestomach, increased
      estrous cycle length, testicular atrophy, and decreased epididymal weight, sperm
      head count, sperm concentration, and sperm motility. The inhalation teratology
      studies did not show maternal or developmental toxicity in Sprague-Dawley rats at
      exposures of up to 7,000 ppm isoprene; in CD-1&reg; Swiss mice, exposure to
      isoprene resulted in lower fetal weights and a higher percentage of fetuses per
      litter with supernumerary ribs. Isoprene was not mutagenic in Salmonella
      typhimurium and did not induce sister chromatid exchanges or chromosomal
      aberrations in Chinese hamster ovary cells with or without exogenous metabolic
      activation; however, in mice, isoprene induced increases in the frequency of
      sister chromatid exchanges in bone marrow cells and in the frequency of
      micronucleated erythrocytes in peripheral blood. These inhalation studies showed
      that isoprene caused toxic effects in the testis of rats and at multiple organ
      sites in mice. In F344/N rats, exposure to 7,000 ppm isoprene for 6 months caused
      an increase in the incidence of testicular interstitial cell hyperplasia, and
      after 6 months of recovery there was a marginally increased incidence of benign
      testicular adenomas that may have been related to isoprene administration. No
      observable-adverse-effect levels (NOAELs) for isoprene-induced toxic lesions in
      mice were: 70 ppm for nonresponsive, macrocytic anemia, decreased hindlimb grip
      strength, olfactory epithelial degeneration, and decreases in epididymal weights,
      spermatid head counts, sperm concentration, and sperm motility; 220 ppm for
      forestomach epithelial hyperplasia; 700 ppm for increased estrous cycle length;
      and 2,200 ppm for testicular atrophy, sciatic nerve degeneration, and muscle
      atrophy. A NOAEL was not achieved for spinal cord degeneration (less than 70 ppm)
      or developmental toxicity (less than 280 ppm, based on lower body weights of
      female fetuses). In addition, the 6-month inhalation exposure plus 6-month
      recovery (stop-exposure) study provided clear evidence of carcinogenicity of
      isoprene in the liver, lung, forestomach, and harderian gland of mice. Because
      these studies involved exposures of male rats and male mice to isoprene for only
      6 months, they do not necessarily reveal the full carcinogenic potential of
      isoprene in these species. Most of the toxic and carcinogenic effects seen with
      isoprene were also caused by inhalation exposure to 1,3-butadiene. Synonyms:
      isopentadiene; 2-methyl-1,3-butadiene; beta-methylbivinyl.

PMID- 12209194
TI  - NTP technical report on the toxicity studies of Dibutyl Phthalate (CAS No. 84-74
      2) Administered in Feed to F344/N Rats and B6C3F1 Mice.
AB  - Dibutyl phthalate is a phthalate ester with extensive use in industry in such
      products as plastic (PVC) piping, various varnishes and lacquers, safety glass,
      nail polishes, paper coatings, dental materials, pharmaceuticals, and plastic
      food wrap. Concomitant with this extensive worldwide use is the high potential
      for human exposure to dibutyl phthalate in the workplace and the home environment
      through direct sources as well as indirectly, through contamination of water,
      air, and foodstuffs. Because existing toxicity information was considered
      inadequate, the effects of exposure to dibutyl phthalate were examined in male
      and female F344/N rats and B6C3F1 mice in 13-week feed studies. Furthermore, due
      to concern over the potential for pervasive exposure of humans to dibutyl
      phthalate, additional perinatal studies examined rats and mice exposed as pups in
      utero, for the 4 weeks of lactation, and for an additional 4 weeks postweaning.
      Additional studies examined the effects on rats of combining perinatal and adult
      subchronic exposure. Due to the recognized biologic activity of this and other
      phthalates, hepatic peroxisome proliferation during the in utero and lactational
      phases and testicular toxicity during the perinatal period were also examined.
      Finally, reproductive assessment by continuous breeding (including crossover
      mating trials and offspring assessment) and genetic toxicity studies were also
      conducted. In the maximum perinatal exposure (MPE) determination study in rats,
      dibutyl phthalate was administered in the diet to dams during gestation and
      lactation, and to the pups postweaning for four additional weeks, at
      concentrations of 0, 1,250, 2,500, 5,000, 7,500, 10,000, and 20,000 ppm.
      Decreased weight gains were noted in dams exposed to 20,000 ppm during gestation
      and to dams exposed to 10,000 ppm during lactation. The gestation index (number
      of live pups per breeding female) was significantly lower in the 20,000 ppm group
      than in the controls, and pup mortality in this group was marked (100% by Day 1
      of lactation); however, survival was 89% or greater in all other treatment
      groups. The mean body weight of pups in the 10,000 ppm group at Day 28 of
      lactation was approximately 90% of the mean weight of control pups. Pups were
      weaned onto diets containing dibutyl phthalate at the same concentrations fed to
      dams. After an additional 4 weeks of dietary administration, final mean body
      weights of pups in the 10,000 ppm groups were 92% of the control value for males
      and 95% of the control value for females. Hepatomegaly (increased relative liver
      weight) was observed in males in all exposed groups and in females receiving
      2,500 ppm or greater. No gross lesions were observed at necropsy. Moderate
      hypospermia of the epididymis was diagnosed in all male rats in the 7,500 and
      10,000 ppm groups; mild hypospermia of the epididymis was diagnosed in 2 of 10
      males in the 5,000 ppm group. No degeneration of the germinal epithelium was
      detected in the testis of these rats. Thus, although toxicologically important,
      the epididymal hypospermia was not considered to be life threatening, and 10,000
      ppm was recommended as the MPE concentration for male and female rats. In the
      subsequent subchronic toxicity study of dibutyl phthalate with perinatal
      exposure, dams were administered diets containing 0 or the MPE concentration
      (10,000 ppm) during gestation and lactation, and weaned pups were administered
      the same diets as their dams received for an additional 4 weeks, until the
      beginning of the 13-week exposure phase. Male and female rats then received diets
      containing dibutyl phthalate at concentrations of 0, 2,500, 5,000, 10,000,
      20,000, and 40,000 ppm for 13 weeks. No mortality or toxicity was observed in
      dams during the perinatal phase of the study; however, before pups were culled at
      4 days postpartum, the percentage of live pups per litter was 86% to 93% that of
      the controls. Through weaning, litter weights of exposed pups ranged from 89% to
      92% of the control values. Ten control and ten exposed pups per sex were examined
      at the time of trol and ten exposed pups per sex were examined at the time of
      weaning; hepatomegaly and markedly increased peroxisomal enzyme activities
      (approximately 9-fold greater than the control values) were observed in exposed
      pups. Body weights of the perinatally exposed pups remained lower than those of
      the controls throughout the 4-week period before the 13-week adult exposures
      began. During the 13-week adult exposure phase, the final mean body weight of
      males in the MPE: 0 ppm control group (MPE rats, returned to the base diet for 13
      weeks), was 95&percnt; that of the controls. The body weight gain of females in
      the MPE:0 ppm group was greater than that of the unexposed controls, and the
      final body weights of these two groups were similar. Body weight gains of rats
      treated with dibutyl phthalate as adults decreased with increasing exposure
      concentration; for rats that received the MPE concentration followed by 40,000
      ppm for 13 weeks, final body weights were 51&percnt; of the control value for
      males and 74&percnt; of the control value for females. Hepatomegaly apparently
      regressed in rats in the MPE:0 ppm groups but was observed in male rats receiving
      5,000 ppm or greater and in females receiving 2,500 ppm or greater. In males that
      received 20,000 ppm as adults, testis and epididymal weights were less than in
      the controls; males in the 40,000 ppm group also had a lower testis weight than
      the controls. Results of hematologic analyses conducted at the end of the 13-week
      exposure period suggested a mild anemia in male rats administered 10,000 ppm or
      greater as adults and female rats administered 40,000 ppm as adults.
      Hypocholesterolemia and hypotriglyceridemia were observed in male and female rats
      at the higher exposure concentrations. Hypotriglyceridemia was detected in
      females receiving 20,000 or 40,000 ppm and in males receiving 10,000 ppm or
      greater. Elevations in alkaline phosphatase activities and bile acid
      concentrations in male and female rats receiving 20,000 or 40,000 ppm as adults
      were indicative of cholestasis. Microscopic examination revealed hepatocellular
      cytoplasmic alteration, consistent with glycogen depletion, in male and female
      rats receiving a concentration of 10,000 ppm or greater. In the liver of rats
      receiving 40,000 ppm, small, fine, eosinophilic granules were also observed in
      the cytoplasm of hepatocytes. Ultrastructural examination suggested the presence
      of increased numbers of peroxisomes. Lipofuscin accumulation was detected in rats
      that received 10,000 ppm or greater. Consistent with the regression of the
      hepatomegaly in rats in the MPE:0 and MPE:2,500 ppm groups, peroxisomal enzyme
      activity was not elevated in these groups. Marked elevations of peroxisomal
      enzyme activity were detected, however, in males receiving 5,000 ppm or greater
      and in females receiving 10,000 ppm or greater; at the 40,000 ppm concentration,
      the highest concentration tested, enzyme activities were approximately 20 fold
      greater than the control values. Histopathologic examination of the testes
      revealed degeneration of the germinal epithelium, a mild to moderate focal lesion
      in rats in the 10,000 and 20,000 ppm groups and a marked, diffuse lesion in all
      males receiving 40,000 ppm; at 40,000 ppm, an almost complete loss of the
      germinal epithelium resulted. Testicular zinc concentrations were lower in the
      40,000 ppm group than in the controls, a finding consistent with the marked loss
      of germinal epithelium at this exposure concentration. Spermatogenesis was
      evaluated in rats in the 0, 2,500, 10,000, and 20,000 ppm groups; rats
      administered 20,000 ppm had fewer spermatid heads per testis than the unexposed
      controls, and epididymal spermatozoal concentration was less than that in the
      MPE:0 ppm group. For comparison with the perinatal subchronic study, a standard
      13-week evaluation of the toxicity of dibutyl phthalate in male and female rats
      was also conducted. In this study, rats received dibutyl phthalate at the same
      dietary concentrations used in the 13-week exposure phase of the study with
      perinatal exposure: 0, 2,500, 5,000, 10,000, 20,000, and 40,000 ppm. No deaths
      occurred in the standard study. Markedly reduced final mean body weights were
      observed in males and females in the 40,000 ppm groups (45&percnt; and 73&percnt;
      of control body weights, respectively); final mean body weights of males
      receiving 10,000 ppm or greater and females receiving 20,000 ppm or greater were
      lower than those of the controls. Hepatomegaly was observed in males that
      received 5,000 ppm or greater and in females that received 10,000 ppm or greater.
      Testis and epididymal weights of males in the 20,000 and 40,000 ppm groups were
      lower than those of the controls. A minimal anemia was detected in male rats
      receiving 5,000 ppm or greater. Hypocholesterolemia was observed in male and
      female rats receiving 20,000 or 40,000 ppm, and hypotriglyceridemia was detected
      in males in all exposed groups and in females receiving 10,000 ppm or greater.
      Elevations in alkaline phosphatase activity and bile acid concentration in male
      and female rats were considered indicative of cholestasis. Morphologic evaluation
      again confirmed the toxicity of dibutyl phthalate to the liver and testes of
      rats. Microscopic examination of the liver revealed hepatocellular cytoplasmic
      alterations, consistent with glycogen depletion, in male and female rats
      receiving 10,000 ppm or greater. In the liver of rats in the 40,000 ppm groups,
      small, fine, eosinophilic granules were also observed in the cytoplasm of
      hepatocytes. Ultrastructural examination suggested the presence of increased
      numbers of peroxisomes, and peroxisomal enzyme activity was elevated in the
      livers of male and female rats administered 5,000 ppm or greater; the enzyme
      activities in the 40,000 ppm groups were approximately 13-fold greater than the
      control value for males and 32-fold greater than the control value for females.
      Lipofuscin accumulation was detected in rats receiving 10,000 ppm or greater.
      Histopathologic examination of the testes revealed degeneration of the germinal
      epithelium, a mild to marked focal lesion in the 10,000 and 20,000 ppm groups and
      a marked, diffuse lesion in all males in the 40,000 ppm group; at 40,000 ppm, an
      almost complete loss of the germinal epithelium resulted. Testicular zinc
      concentrations were lower in the 20,000 and 40,000 ppm groups than in the
      controls. Serum testosterone values were also lower at these concentrations than
      in the controls. Spermatogenesis was evaluated in males in the 0, 2,500, 10,000,
      and 20,000 ppm groups; at 20,000 ppm, spermatid heads per testis and per gram
      testis, epididymal spermatozoal motility, and the number of epididymal
      spermatozoa per gram epididymis were lower than in the controls. All of these
      findings are consistent with the marked loss of germinal epithelium at these
      exposure concentrations. In the continuous breeding study, Sprague-Dawley rats
      received 0, 1,000, 5,000, or 10,000 ppm dibutyl phthalate in feed. Mean body
      weights of exposed dams at delivery and during lactation generally decreased with
      increasing exposure concentration. The mean pup weight at birth in the 10,000 ppm
      group was significantly lower than the control pup weight. The average number of
      live pups per litter in all exposed groups was lower than in the controls.
      Crossover mating trials in the F(0) generation revealed no effects on the
      fertility of male or female rats receiving 10,000 ppm. In contrast to the F(0)
      rats, mating, pregnancy, and fertility indices of F(1) rats were lower in the
      10,000 ppm group than in the controls. Germinal epithelial degeneration of the
      testes and absence or under development of the epididymides were noted in F(1)
      males in the 10,000 ppm group. Interstitial cell hyperplasia was noted in 7 of 10
      males in the 10,000 ppm group. These effects document the male and female
      reproductive toxicity of dibutyl phthalate in F(1) rats receiving 10,000 ppm and
      do not exclude the possibility of developmental toxicity to F2 offspring. In the
      MPE determination study in mice, dams received 0, 1,250, 2,500, 5,000, 7,500,
      10,000, or 20,000 ppm dibutyl phthalate in feed during gestation and lactation;
      pups were weaned onto the same diets as the dams received and were exposed for an
      additional 4 weeks. The gestation period was longer in dams that received 2,500
      ppm or greater than in the controls, and gestational body weight gain depressions
      were noted in dams receiving 7,500 ppm or greater. Only 5 of 20 females in the
      10,000 ppm group delivered live pups, and none of the 20 females receiving 20,000
      ppm delivered live pups. Only one pup in the 10,000 ppm group survived past
      Lactation Day 1; the number of live pups per litter in the 7,500 ppm group also
      remained low throughout lactation. No deaths of either male or female pups
      occurred after weaning. Initial (postweaning) and final body weights of male pups
      receiving 2,500 ppm or greater were significantly less than those of the control
      group. The mean body weights of exposed female pups were similar to the control
      body weight at weaning and remained similar throughout the 4 weeks postweaning.
      Hepatomegaly was present in male mice in all exposed groups, and the absolute
      liver weight of males administered 7,500 ppm was greater than that of the
      controls; although a similar change was apparent in females, no statistical
      differences between the liver weights of exposed and control females were
      detected. No treatment-related gross lesions were identified at necropsy, and no
      histopathologic lesions definitively associated with treatment were observed in
      male or female mice in the 7,500 ppm groups. The one surviving male pup in the
      10,000 ppm group had cytoplasmic alteration in the liver, consistent with
      peroxisome proliferation. Developmental toxicity and fetal and pup mortality were
      suggested at concentrations as low as 7,500 ppm. No subchronic toxicity study
      with prior MPE exposure was conducted with mice, although an MPE concentration of
      5,000 ppm was suggested by the data. In a standard 13-week toxicity study, mice
      received 0, 1,250, 2,500, 5,000, 10,000, or 20,000 ppm dibutyl phthalate in feed.
      No deaths occurred during this study. Mean body weights and weight gains of male
      and female mice decreased with increasing exposure concentration, and the
      decreases were significant for males and females that received 5,000 ppm or
      greater. Relative liver weights were greater in males and females receiving 5,000
      ppm or greater than in the controls. A minimal anemia was suggested in female
      mice in the 20,000 ppm group. Although no gross lesions were observed at
      necropsy, microscopic examination revealed hepatocellular cytoplasmic
      alterations, consistent with glycogen depletion, in male mice receiving 10,000 or
      20,000 ppm and female mice receiving 20,000 ppm. Small, fine, eosinophilic
      granules, consistent with peroxisome proliferation, were also observed in the
      cytoplasm of hepatocytes in males and females in the 20,000 ppm groups.
      Lipofuscin accumulation in the liver was detected in mice receiving 10,000 ppm or
      greater. In a continuous breeding study using Swiss (CD-1&reg;) mice, animals
      received 0, 300, 3,000, or 10,000 ppm dibutyl phthalate in feed. The fertility
      index, average number of litters per breeding pair, and average number of live
      pups per litter in the 10,000 ppm group were lower than in the controls.
      Crossover mating trials of mice receiving 10,000 ppm revealed effects on dams in
      the F(0) generation, with a lower fertility index, number of live pups per
      litter, and pup weight than in the controls. Liver weights were greater in males
      and females, and the uterine weight was less in exposed dams than in the
      controls. No other changes were observed at necropsy or on histopathologic
      examination. These data document the female reproductive toxicity of dibutyl
      phthalate in F(0) mice. Dibutyl phthalate was not mutagenic in Salmonella
      typhimurium strain TA98, TA100, TA1535, or TA1537 with or without exogenous
      metabolic activation but did induce mutations in L5178Y mouse lymphoma cells
      treated without metabolic activation. In peripheral blood samples obtained from
      male and female mice at the end of the 13-week study, frequencies of
      micronucleated normochromatic erythrocytes were similar between exposed and
      control mice. Together, the studies in rodents suggest that young rodents (in
      utero and perinatal) respond in a manner qualitatively similar to that of adult
      rats and mice. Dibutyl phthalate induced toxic effects in rodents as pups in
      utero and during the lactational phases of development and also affected young
      adults, as evidenced by fetotoxicity and lethality, body weight gain decrements,
      increased liver weights, hepatic peroxisome proliferation, testicular toxicity,
      and female reproductive toxicity. Dibutyl phthalate was lethal to rat fetuses and
      rat and mouse neonates at dietary concentrations that were not toxic to dams.
      Otherwise, there was no teratogenic or morphologic evidence that rodent young
      were uniquely sensitive to the effects of short-term dibutyl phthalate treatment.
      Synonyms: 1,2-Benzenedicarboxylic acid dibutyl ester; benzene-o-dicarboxylic acid
      di-n-butyl ester; o-benzenedicarboxylic acid dibutyl ester; butyl phthalate; n
      butyl phthalate; DBP; dibutyl 1,2-benzene dicarboxylate; dibutylphthalate; di-n
      butylphthalate; di(n-butyl) phthalate; dibutyl-o-phthalate; phthalic acid dibutyl
      ester. Trade Names: Celluflex DBP; Elaol; Ergoplast FDB; Ersoplast FDA; Genoplast
      B; Hexaplas M/B; Palatinol C; Polycizer DBP; PX 104; RC Plasticizer DBP; Staflex
      DBP; Uniflex DBP; Unimoll DB; Witcizer 300; Witicizer 300. (NOTE: These studies
      were supported in part by funds from the Comprehensive Environmental Response,
      Compensation, and Liability Act trust fund (Superfund) by an interagency
      agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public
      Health Service.)

PMID- 12209195
TI  - NTP technical report on the toxicity studies of Cupric Sulfate (CAS No. 7758-99
      8) Administered in Drinking Water and Feed to F344/N Rats and B6C3F1 Mice.
AB  - Cupric sulfate is an inorganic salt which is widely used in industry,
      agriculture, and veterinary medicine. Its applications include use as an algicide
      in potable waters and as a feed additive and therapeutic agent in swine, sheep,
      and cattle. Because copper salts are found in human water supplies, toxicity
      studies of cupric sulfate pentahydrate were conducted in male and female F344/N
      rats and B6C3F1 mice by the drinking water (2-week studies only) and dosed feed
      routes (2-week and 13-week studies). Animals were evaluated for hematology,
      clinical chemistry, urinalysis, reproductive toxicity, tissue metal accumulation,
      and histopathology. In the 2-week drinking water studies, groups of five rats and
      five mice per sex received cupric sulfate at concentrations of 300 to 30,000 ppm
      for 15 days. One female rat, one male mouse, and three female mice in the 3000
      ppm groups and all rats and mice in the 10,000 and 30,000 ppm groups died before
      the end of the studies. The remaining mice and rats in the 3000 ppm groups gained
      little or lost weight. Water consumption in the three highest dose groups of both
      species was reduced by more than 65%. Clinical signs observed in these groups
      were typical of those seen in moribund animals and were attributed to
      dehydration. The only gross or microscopic change specifically related to cupric
      sulfate toxicity was an increase in the size and number of cytoplasmic protein
      droplets in the epithelium of the renal proximal convoluted tubule in male rats
      from the 300 and 1000-ppm groups. In the 2-week feed studies, groups of five rats
      and five mice per sex were fed diets containing 1000 to 16,000 ppm cupric
      sulfate. No chemical-related deaths occurred in any dose group. Compared to the
      controls, rats and mice in the two highest dose groups had reduced body weight
      gains which were attributed to decreased feed consumption. Hyperplasia with
      hyperkeratosis of the squamous epithelium on the limiting ridge of the
      forestomach was seen in rats and mice of each sex; this lesion was more severe in
      rats than in mice. Inflammation of the liver, periportal to midzonal in
      distribution, occurred in rats in the 8000 and 16,000 ppm groups. Depletion of
      hematopoietic cells was evident in rats of each sex in the bone marrow (8000 and
      16,000 ppm) and spleen (16,000 ppm). Kidneys of male and female rats in the 4000,
      8000, and 16,000 ppm groups had an increased number and size of protein droplets
      in the epithelia of the renal cortical tubules. In the 13-week feed studies,
      groups of 10 rats per sex received diets containing 500 to 8000 ppm cupric
      sulfate, and groups of 10 mice per sex received diets containing 1000 to 16,000
      ppm cupric sulfate for 92 days; estimates of cupric sulfate consumption ranged
      from 32 to 551 mg/kg per day for rats and 173 to 4157 mg/kg per day for mice.
      There were no chemical-related deaths in rats or mice, and no clinical signs of
      cupric sulfate toxicity were recorded. Final mean body weights were lower than
      those of the controls for animals of both species receiving doses of 4000 ppm
      cupric sulfate and greater. In mice in the 13-week studies, there was a dose
      related decrease in liver weights. Hematologic, clinical chemistry, and
      urinalysis evaluations of rats in the 13-week study revealed variable chemical
      related changes that were, for the most part, restricted to the 4000 and 8000 ppm
      groups. Increases in serum alanine aminotransferase and sorbitol dehydrogenase
      activities in both sexes were indicative of hepatocellular damage, as were
      increases in 5'-nucleotidase and bile salts in males. Decreases in mean cell
      volume, hematocrit, and hemoglobin indicated the development of a microcytic
      anemia, while increases in reticulocyte numbers at the same time points suggested
      a compensatory response to the anemia by the bone marrow. Increases in urinary
      glucose and N-acetyl-beta-D-glucosaminidase (a lysosomal enzyme) and aspartate
      aminotransferase (alpha-cytosolic enzyme) were suggestive of renal tubule
      epithelial damage. Dose-related increases in copper occurred in all male rat
      tissues examined (lissues examined (liver, kidney, plasma, and testis). These
      increases were accompanied by increases in zinc in the liver and kidney. Plasma
      calcium was significantly reduced in the 4000 and 8000 ppm groups, and there was
      a trend toward reductions in calcium in the kidney and testis as well. In the
      8000 ppm group, plasma magnesium was significantly increased relative to the
      controls. Rats in the three highest dose groups had hyperplasia and
      hyperkeratosis of the forestomach, inflammation of the liver, and increases in
      the number and size of protein droplets in the epithelial cytoplasm and the
      lumina of the proximal convoluted tubules. These effects were similar to those
      seen in the 2-week feed study, and the incidence and severity of these lesions
      were dose related. Many of the droplets in male rat kidneys were large and had
      irregular crystalline shapes. These droplets stained strongly positive for
      protein but were negative by iron, PAS, and acid-fast (lipofuscin) staining
      methods. &alpha;-2-Microglobulin was present in the droplets of male rats, but
      there was no dose- related, qualitative difference in the content of this
      protein. In the 4000 and 8000 ppm groups, copper was distributed in a periportal
      to midzonal pattern in the liver and was restricted to the cytoplasm of the
      proximal convoluted tubule epithelium in the kidney. Copper was present in some,
      but not all, of the protein droplets. Transmission electron microscopy of the
      livers of rats of each sex revealed increases in the number of secondary
      lysosomes in hepatocytes in the periportal area. In mice of each sex receiving
      4000 ppm cupric sulfate and higher in the 13-week study, there was a dose-related
      increase in hyperplasia with hyperkeratosis of the squamous mucosa on the
      limiting ridge of the forestomach. Minimal positive staining for copper was
      present in the liver and was limited to high-dose (16,000 ppm) male and female
      mice. Cupric sulfate produced no adverse effects on any of the reproductive
      parameters measured in rats or mice of either sex. In summary, administration of
      cupric sulfate to rats in feed or drinking water resulted in significant gastric
      changes and hepatic and renal damage. The primary lesion in rats was an increase
      in the size and number of proteinaceous droplets in the epithelial cytoplasm and
      lumen of the proximal convoluted tubule. For rats in the 13-week study, the no
      observed-adverse-effect level (NOAEL) for evidence of histologic injury to the
      kidney was 1000 ppm for males and 500 ppm for females, while the NOAEL for liver
      inflammation was 1000 ppm for males and 2000 ppm for females. Hyperplasia with
      hyperkeratosis of the epithelium on the limiting ridge separating the forestomach
      from the glandular stomach was also seen in rats of each sex, and the NOAEL for
      this change was 1000-ppm cupric sulfate in the feed. Additionally, clinical
      pathology alterations noted in the 13-week study, along with histologic changes
      in bone marrow noted in the 2-week feed study, were indicative of a microcytic
      anemia with a compensatory bone marrow response. Mice appeared to be much more
      resistant to the toxic effects of cupric sulfate than rats. The primary target
      tissue in mice was the epithelium of the limiting ridge of the forestomach. The
      NOAEL for the hyperplasia and hyperkeratosis seen at this site in mice was 2000
      ppm cupric sulfate in the feed. Synonyms: Chalcanthite; Copper sulfate; cupric
      sulfate pentahydrate; bluestone; blue vitriol; Roman vitriol; Salzburg vitriol.
      (NOTE: These studies were supported in part by funds from the Comprehensive
      Environmental Response, Compensation, and Liability Act trust fund (Superfund) by
      an interagency agreement with the Agency for Toxic Substances and Disease
      Registry, U.S. Public Health Service.)

PMID- 12209196
TI  - Understanding the causes of health inequalities: incorporating personal, local,
      national, and global perspectives.

PMID- 12209197
TI  - What if New South Wales were more equal?

PMID- 12209198
TI  - Health, wellbeing and progress.

PMID- 12209199
TI  - Social capital and public expenditure in Australia.

PMID- 12209201
TI  - Globalisation and health.

PMID- 12209202
TI  - FactSheet: HIV and AIDS.

PMID- 12209200
TI  - Social inclusion and the public health: the case for partnerships.

PMID- 12209203
TI  - Communicable diseases, New South Wales: June 2002.

PMID- 12209205
TI  - Fatal work injuries in New South Wales.

PMID- 12209206
TI  - Farm-related injury in New South Wales: information for prevention.

PMID- 12209207
TI  - Australian approaches to the prevention of farm injury.

PMID- 12209208
TI  - Tractor safety in New South Wales--ROPS Retro-fitment Campaign.

PMID- 12209209
TI  - Child Safety on Farms strategy.

PMID- 12209210
TI  - Counting the cost of work-related injuries and diseases in poultry farming in New
      South Wales.

PMID- 12209211
TI  - Q Fever Register developed to address health concern in the meat industry.

PMID- 12209212
TI  - Release of Program for Enhanced Population Health Infostructure (PEPHI): a report
      of responses to the November 2000 discussion paper.

PMID- 12209213
TI  - FactSheet: Salmonellosis.

PMID- 12209214
TI  - Communicable diseases, New South Wales: May 2002.

PMID- 12209215
TI  - [GASTROENTEROLOGY AND HEPATOLOGY : NEXT MILLENNIUM]

PMID- 12209216
TI  - [HEPATITIS B AND C VIRUS INFECTION AS RISK FACTORS FORHEPATOCARCINOMA IN PERU:
      CASE AND CONTROL STUDY]
AB  - To investigate whether past exposure to Hepatitis B virus (HBV) and Hepatitis C
      Virus (HCV) were risk factors for the development of Hepatocellular Carcinoma
      (HCC) in Peru, a case-control study of 136 patients with HCC and 136 age-matched
      and sex-matched control subjects was performed. Past exposure to HBV and HCV were
      assessed respectively by antibody to hepatitis B core antigen (Anti-HBc) and
      HbsAg and anti-HCV.Of the HCC cases, 63.2% were posuitive for HbsAg and 0.73%
      foranti-HCV. Of the control patients, 4.4% were positive to HbsAg and 0.73% to
      anti-HCV.The mean age of patients with HCC negative for HbsAg was significantly
      greater than that of patients HCC positive for HbsAg (35.4 versus 29.4 years, p
      less than 0.001).The HbsAg patients are 36.26 times more prone to developing HCC
      than those with HbsAg negative (95% confidence interval: 15.31-90.7).Infection
      with HCV does not pose a risk for the development of HCC (RR 1, 95% confidence
      interval: 0.062-16.152).A causal relation between HBV infection in children HCC
      was observed. These results indicate that HbsAg carriage is a risk factor for HCC
      in Peru. The importance of vertical or perinatal transmission of HBV and the
      prophylactic role of passive immunization plus vaccination during childhood is
      emphasized as well as the selective vaccination of high risk groups.

PMID- 12209217
TI  - [ENDOSCOPIC TREATMENT OF EARLY GASTRIC CANCER ANDPRECANCEROUS GASTRIC LESIONS
      WITH MUCOSECTOMY]
AB  - The endoscopic treatment of early gastric cancer with mucosectomy has
      increasingly proved to be an effective modality for local treatment, especially
      if the tumor is limited to the mucosa, of a size no greater than 3 cm, with no
      histologic ulceration nor lymphatic vessel invasion and a cancer-negative
      resection line. The mucosectomy has also proved to be useful in the resection of
      precancerous lesions such as adenomas. Over a period of two years (1996-1997),
      five patients (three men and two women), who were diagnosed early gastric cancer
      (four of them) and adenoma with moderate dysplasia (one of them), were treated
      with mucosectomy using a conventional endoscopic snare and pure coagulation
      current. A plecemeal technique was used to achieve complete removal in two of
      these patients.In all five cases complete removal was achieved in a single
      session with no complications. Two patients underwent radical surgery with not
      tumor remnant or metastatic lymph node present in the resected specimen. All
      patients have remained free of recurrence during an mean follow-up period of
      sixteen months (range of 9-29 months).The early gastric cancer and gastric
      adenomas can be sultably removed with mucosectomy by the appropriate selection of
      patients.

PMID- 12209218
TI  - [ENDOGENOUS INTRAGASTRICAL MICROFLORA IN GASTRIC CANCER]
AB  - The aim of this prospective study was to identify the type of microbial flora and
      additionally to correlate the total number of microorganisms with factors such as
      age, tumoral area, and the pH gastric in unaffected gastric mucosal biopsies
      obtained during gastrojejunostomy (n=5) or gastrectomy (n=1) in patients with
      gastric adenocarcinoma (n=15) or lymphoma (n=1) at the Belen Hospital, Trujillo,
      Peru, between January 1, 1996 and April 30,1998. The mean age of the patients was
      54.4 + 18.3 years (range: 20 to 79 years) with a male:female ratio of 1:2,2.
      Fifteen of the patients (93.7%) were colonized. Aerobic species found in 7/15
      (46.7%), 5/15 (33.3%) showed a mixed aerobic and anaerobic bacterial growth, 1/15
      (6.7%) had growths of aerobic microorganisms and yeasts, and only 2/15 (13.3%) of
      the patients harbored yeasts. Gram-negative aerobic and gram-positive species
      were present in 4/7 (57.1 %) and 3/7 (42.9%) of the patients, respectively. In
      those patients who had a mixed bacterial growth, peptostreptococcus were the most
      common findings in 5/5 (100%) of the patients, and Helicobacter pylori was
      isolated only in one case. A gastric pH of 4 or more was found in 14/16 of the
      patients examined and 12 of them (85%) had growth of microorganisms. There was no
      significant statistical correlation among the pH of the gastric juice, age or
      tumoral area and the total number of microorganisms/gram in mucosal biopsies of
      the 7 cases evaluated. Antibiotic agents used as a prophylaxis in gastric cancer
      surgery should cover both aerobic and anaerobic microorganisms, especially those
      patients with a pH of 4 or more.

PMID- 12209220
TI  - [FULMINANT HEPATIC FAILURE IN CHILDREN]
AB  - This study describes the etiology, clinical and laboratory characteristics of
      Fulminant Hepatic Failure in a pediatric population of 29 patients, of the
      Instituto Nacional del Nino, Lima, Peru. In eleven (11) of them, the etiology
      could not be established. HAV wasthe most frequent etiology, with 8 patients
      (44.4%) followed by inorganic phosphorus poisoning with 5 patients (27.7%). The
      mean age was 5 years and 4 months; encephalopathy followed by vomiting were the
      main symptoms and/or signs prompting the admittance of the children. The duration
      of the illness was 14.6 days and the time between the appearance of jaundice and
      the onset of encephalopathy was 6.65 days, the lesser the time the poorer the
      prognosis. The most frequent symptom in the physical exam was hepatomegaly
      followed by jaundice and encephalopathy. During its evolution all patients showed
      signs of encephalopathy and jaundice. The short protrombine time and the high
      rate of transaminases correlated with an improved prognosis and the Aspartate
      transaminase and bilirrubines were higher in the infectious causes. The mortality
      rate was 69%. The most frequent complication was upper gastro-intestinal
      bleeding, continued by hydroelectrolyte imbalance.

PMID- 12209219
TI  - [DIGESTIVE TUBERCULOSIS IN THE EDGARDO REBAGLIATI MARTINSHOSPITAL (HNERM): A
      RETROSPECTIVE STUDY OVER A FIVE-YEAR PERIOD (1993-1998)]
AB  - INTRODUCTION: Tuberculosis is a common disease in Peru.Although there is evidence
      of the decrease in lung infections, abdominaltuberculosis and other
      extrapulmonary varieties show an increase in incidence. This study was performed
      in order lo determine incidence, clinical picture, diagnostic methods and
      procedures, compromised tissues and organs and treatment given to patients with
      Digestive Tuberculosis in the Hospitalization Area of the Digestive Disease
      Department of the Peruvian "Edgard Rebagliati Martins" Hospital in Lima-Peru, a 1
      500 bed Center. METHODS: 77 clinical records were reviewed, of patients
      discharged and diagnosed with Abdominal or Digestive Tuberculosis between January
      1993 to May 1998. Fifty eight of these records fuifilled the requirements.
      Results: The mean duration of symptoms was 5.49 months. The clinical
      characteristics are unspecific. The most frequent symptoms were weight loss,
      chronic diarrhea, abdominal pain and fever (over 70% of cases). The most common
      signs were abdominal pain, ascites and cachexia in more than 50% of the cases.
      The Laboratory tests are typical for chronic diseases and emphasize the
      erythrocite sedimentation rate that was high in 98% of cases. Adenosin Deaminase
      Assay (ADA) in ascific fluid was high in 95% of cases when peritoneal compromise
      was present and fluid could be obtained. The Radiology tests such as barium colon
      enema and intestinal transit tests were helpful together with Ultrasound and
      Computerized Tomography in detecting the intestinal location of the disease, the
      organs that had been affected as well assisting as to the decision to perform
      further invasive tests. We found 27.58% with gastrointestinal location, 43% with
      only peritoneal affection and 27.58% of mixed forms (gastrointestinal plus
      peritoneal). The endoscopic procedures have been decisive for the diagnosis of up
      to 90% of cases and Laparascopy has been of value, in up to 70% of the cases, for
      the detection of peritoneal affection. Six patients of our series have required
      exploratory Laparascopy for diagnosis. Treatment has been effective in 86% of
      cases. CONCLUSION: The diagnosis of Digestive Tuberculosis continues to be long,
      tedious and expensive. The incidence of this disease has increased in our
      Hospitalization Center since 1993. All cases reviewed require invasive procedures
      (endoscopic) or surgery for their final diagnosis. We emphasize the use of
      Laparoscopy tests for the evaluation of p0eritoneal affection.

PMID- 12209221
TI  - [PERITONEAL VENOUS SHUNT IN THE TREATMENT OF MALIGNANTASCITIS: PRELIMINARY
      REPORT]
AB  - The present study, mentions the use of a valve for the drainage os ascitic fluid,
      better known as the peritoneo venous shunt, as a paliation treatment in terminal
      oncologic patients. It was performed in four patients with diseminated
      carcinomas, of diferent primary ethiology. These patients had a bad life quality,
      because when admitted in our Radiology suite, the clinical examination showed
      shortness of breathearly saciety, lethargy, and were found handiccapped to
      perform their habitual skills. This is a short and preliminar series, but it is
      an encouraging report, because, the quality of life, our goal, is improved.

PMID- 12209222
TI  - [INGESTION OF CORROSIVE SUBSTANCES]
AB  - Every patient that ingests any caustic substance still constitutes a medical and
      surgical. The severity and extension of the chemical damage will basically depend
      on the concentration and quantity of the caustic substance ingested. Likewise,
      when a highly concentrated alkali or acid substance is ingested, the esophagus
      and stomach will be damaged, and this lesion could also spread to the duodenum,
      and in some cases to the jejunum. Furthermore, it may compromise adjacent organs
      with a high morbimortality. The severity degree of the lesion can be determined
      with no risk by a flexible endoscopy, and correlates well with the intensity of
      tissue damage, enabling us to decide the manner in which this lesion is to be
      handled, with a prognosis value. A superficial grade (1 or 2a),will require no
      treatment and it will evolve without sequela. However, upon the determination of
      deep, ulcerated circumferential lesions, or with necrotic fundus by endoscopy
      (Grade 2b, and 3), patients shall be hospitalized and shall receive enteral or
      parenteral nutrition, as well as antibiotic protection. Careful attention should
      be given due to the risk of perforation or hemorrhage, and ocasionally, urgent
      surgical treatment will be necessary.The use of corticosteroids has proved to be
      innefective in preventing stenosis and is potentially dangerous. The most
      frequent late sequela is the developing of esophageal stenosis (developing in 50
      70% of the 2b, and in all of the 3 who survive), and antral stenosis. The
      esophageal stenosis are tributaries of dilatations with bougies. An option to
      avoid stenosis, specially in children, is the placement of short plastic tubes,
      temporarily. In cases where there is no good response to the dilatations. or when
      the stenosis are long and multiple, surgery with interposition of colon or
      jejunum will be necessary. Usually, the development of gastric stenosis requires
      surgery. Motor alterations and gastroesophageal reflux as sequela may also be
      present, and belatedly, a greater risk to develoop squamous cancer.

PMID- 12209223
TI  - [SUCCESSFUL HANDLING OF HEMORRHAGES DUE TO JEJUNALVARICEAL VEIN WITH
      SCLEROTHERAPY AND ENDOLIGATURE: A REPORT ON ONE CASE]
AB  - A case of jejunal bleeding is reported. A 68-year-o1d man, who suffered previous
      gastrectomy and sclerotherapy for esophageal varices presented jejunal variceal
      bleeding. These varices were sclered and banded with good results.

PMID- 12209224
TI  - [ACUTE MESENTEROAXIAL GASTRIC VOLVULUS: A REPORT ON ONE CASE]
AB  - Acute gastric volvulus in children is uncommon. This paper reports a case
      presented in a 14-year-old female whose diagnosis was suspected preoperatively
      taking into account the Brouchardt triad (vomiting, epigastric pain and inability
      to pass the nasogastric tube into the stomach). The child underwent laparatomy
      and the final diagnosis was mesenteroaxial gastric volvulus complicated with
      gastric perforation. Closure of the perforation and gastropexy were performed and
      the operative results were satisfactory.

PMID- 12209225
TI  - [RETROGRADE ENDOSCOPIC CHOLANGIO PANCREOTOGRAPHY(PCRE)AND PAPILLOSPHINCTERECTOMY:
      A REPORT ON TWO CASES]
AB  - We report two paediatric patients diagnosed with Cholellithiasis and
      Choledocolithiasis who underwent Laparoscopic Cholecystectomy and
      Papillosphincterectomy.

PMID- 12209226
TI  - [COLONIC PARACOCCIDIOIMYCOSIS: A REPORT ON ONE CASE]
AB  - We present a 36-year-old patient with colonic paracoccidiodomycosis. The
      epidemiological, clinical, laboratory, radiological, pathological features and
      treatment of this unusual disease were reviewed.

PMID- 12209227
TI  - Trans-mediastinal gunshot wounds: are "stable" patients really stable?
AB  - Gunshot wounds that traverse the mediastinum frequently cause serious injury to
      the cardiac, vascular, pulmonary, and digestive structures contained within. Most
      patients present with unstable vital signs signifying the need for emergency
      operation. An occasional patient will present with stable vital signs. Work-ups
      for such a patient may range from surgical exploration to radiographic and
      endoscopic testing to mere observation. We report our experience with diagnostic
      work-up of the stable patient with a transmediastinal gunshot wound. All stable
      patients who present to our urban level I trauma center following a
      transmediastinal gunshot wound undergo diagnostic work-up consisting of chest
      radiograph, cardiac ultrasound, angiography, esophagoscopy, barium swallow, and
      bronchoscopy. The work-up is dependent on the trajectory of the missile.
      Information on these patients is kept in a prospective database maintained by the
      trauma attending physicians. This database was analyzed and comparisons were made
      using Student's t-test and the Fisher exact c2 as appropriate. Over a 68-month
      period, 50 stable patients were admitted following a transmediastinal gunshot
      wound. All of these patients had a chest radiograph followed by one or more of
      the above tests. 8 patients (16%) were found to have a mediastinal injury (4
      cardiac, 3 vascular, and 1 tracheo-esophageal) requiring urgent operation (group
      1). The remaining 42 patients (84%) did not have a mediastinal injury (group 2).
      There was no difference between groups with respect to blood pressure, pulse,
      respiratory rate, pH, base deficit, or initial chest tube output. There was one
      death in each group, and three complications in group 2. Patients may appear
      stable following a transmediastinal gunshot wound, even when they have life
      threatening injuries. There is no difference in vital signs, blood gas, or
      hemothorax to indicate which patients have serious injuries. We advocate
      continued aggressive work-up of these patients to avoid missing an injury with
      disastrous consequences.

PMID- 12209228
TI  - Tetanus: continuing problem in the developing world.
AB  - Despite diligent efforts by the World Health Organization and the governments of
      developing world countries, tetanus persists as a global health problem. This
      retrospective study was undertaken to assess the outcome for victims of tetanus
      presenting to the Baptist Medical Centre in Ogbomoso, Nigeria and to develop
      better management techniques for future patients. Sixty patients (46 males, 14
      females) with nonneonatal tetanus were seen over a 5-year period (1995-1999). The
      mean age was 26 years, and 74% were 30 years or younger. All patients were
      treated with antitetanus serum, antibiotics, wound debridement (when a wound was
      identified), and antispasmodics. No patients underwent tracheostomy or
      gastrostomy. The mortality rate was 44%. Factors significant for predicting
      mortality were age greater than 14 years, occupation as a farmer, short
      incubation period, short symptom duration, high degree of severity on
      presentation, and high temperature during hospital care. The best hope for
      improvement in the treatment of tetanus in our institution is more conscientious
      titration of antispasmodics to control spasms without causing significant
      respiratory depression. The only real hope for reducing the global mortality for
      tetanus, however, lies in renewed immunization efforts by all health care
      providers in developing world countries, not just community health workers.

PMID- 12209229
TI  - Necessity of axillary dissection in elderly women with early breast cancer.
AB  - The need for axillary dissection for staging and treating early breast cancer has
      been questioned recently. Can a patient forego axillary dissection, with its
      associated costs, risks, and morbidity, if it does not affect survival? The study
      attempted to find a subset of patients with early breast cancer in whom disease
      free survival was independent of axillary lymph node status. If survival does not
      depend on lymph node status, axillary dissection could be omitted in the care of
      these patients. This study included 378 women over age 70 with T1 breast cancer
      diagnosed and treated during January 1992 to December 1999 at both of our
      institutions: a large tertiary teaching hospital in Columbus, Ohio and a breast
      cancer treatment center in West Columbia, South Carolina. We compared the disease
      free survival, using the Kaplan-Meier estimate, in 334 node-negative patients and
      44 node-positive patients with T1 breast cancer. The 3- and 5-year survival rates
      of patients with T1N0 tumors were 86% and 77%, respectively; and the 3- and 5
      year survival rates for T1 node-positive tumors were 81% and 69%, respectively (p
      = 0.0673). There was no statistical difference between the node-negative and node
      positive groups. Axillary dissection in women over 70 years of age with early
      breast cancer may be unnecessary, as the presence of lymph node metastases does
      not appear to affect disease-free survival rates significantly in this patient
      group.

PMID- 12209230
TI  - Early experience with the Nuss minimally invasive correction of pectus excavatum
      in adults.
AB  - Nuss described a minimally invasive technique for correcting pectus excavatum in
      children. A curved stainless-steel bar is inserted behind the sternum through the
      chest cavity with the convex surface face down, then rotated 180 degrees to
      elevate the sternum and correct the deformity. The procedure gained wide
      acceptance in children. The purpose of this study was to determine if the
      procedure is effective in adults. Only patients with symptoms limiting lifestyle,
      chest wall indices higher than 3.25, and demonstrable cardiac compression on
      echocardiography were accepted. Between April 1998 and January 2001, 14 adults
      aged 19 to 46 underwent assessment for the Nuss minimally invasive technique for
      correction of pectus excavatum. Eight patients, 19 to 32 years of age, met the
      stated criteria for acceptance. The comorbidities were 2 asymmetrical
      deformities, 2 scolioses, 1 previous pectus repair, and 1 previous breast
      augmentation. The patients were informed of the benefits and disadvantages of
      both the Ravitch and the Nuss procedures. All patients except the first had
      talked to one or more adults who previously had the procedure. Follow-up was 7 to
      37 months (mean 22.1 months). Four patients have had their bars removed and
      maintained correction. Success of the operation was based on relief of cardiac
      compression, alleviation of symptoms, and adequate pain control. Operating time
      was 1 to 2:05 hours (mean 1:32 hours). Complications were pneumothorax in one
      patient, urinary retention in 2, and left lower lobe atelectasis in 5.
      Complications did not prolong hospitalization. Postoperative epidural analgesia
      was discontinued after 2 to 4 days (mean 2.8 days). Average daily pain scores
      were between 1.6 and 3.7 on a scale of 0 to 10. Hospital stay was 3 to 5 days
      (mean 4 days). Relief of symptoms and increase in activity were obtained in all
      patients. Relief of cardiac compression was demonstrated in the 6 patients who
      have had postoperative echocardiograms. Patients returned to normal activity 2 to
      4 weeks postoperatively (mean 2.3 weeks). Duration of pain medicine was 2 to 4
      weeks in 6 patients and 2 and 4 months for the other 2 (mean 5.5 weeks). There
      were 2 late complications related to the bar, but without loss of correction. The
      early experience with the Nuss minimally invasive pectus excavatum repair in
      adults is encouraging. The procedure is effective for correcting pectus excavatum
      in selected patients. Early results are dependent upon adequate bar stabilization
      and pain control. The long-term results in adults are unknown.

PMID- 12209231
TI  - Barrett's esophagus complicated with stricture: correlation between
      classification and the results of the different therapeutic options.
AB  - Benign esophageal stricture is a serious complication of persistent
      gastroesophageal reflux in patients with esophagitis and Barrett's esophagus. A
      classification of the severity of the stricture is proposed, based on its
      internal diameter, its length, and the ease or difficulty in dilating it. Among
      185 patients with esophageal strictures secondary to reflux esophagitis, 77
      (41.6%) corresponded to type I or mild stricture, 73 (39.4%) to type II or
      moderate, and 35 (19.6%) to type III. Medical treatment was performed in only 15
      cases, with 73% recurrence. Three types of surgical procedures were employed,
      always after dilatation, improvement of nutritional status, and a complete
      preoperative work-up: (1) conservative antireflux surgery, which had a high
      incidence of recurrence (41.1%); (2) acid suppression and duodenal diversion, in
      which 68 patients had a mortality rate of 2.9% and a recurrence rate of 4.4% (p
      <0.002); and (3) esophageal resection, which in 7 patients resulted in 1 death
      and no late recurrence. It is concluded that classification of the severity of
      the stricture is important to indicate the most appropriate treatment.
      Conservative antireflux surgery is followed by a high recurrence rate at late
      follow-up, whereas acid suppression and duodenal diversion seem to be an adequate
      procedure that is followed by a very low recurrence rate. Esophageal resection is
      indicated only for patients with severe or critical esophageal strictures.

PMID- 12209232
TI  - Choledocholithiasis: new approach to an old problem.

PMID- 12209234
TI  - Surgery of chronic pancreatitis: chronicle of confusion and despair.
AB  - The evolution of surgery for pancreatitic disease has been arduous owing to the
      technical difficulties of addressing the organ and the lack of understanding the
      mechanisms of the disease processes involving it. In particular, the tardy
      advance of surgery in the management of chronic pancreatitis exemplifies these
      problems. Because no specific target has been identified, mechanical intervention
      has for the most part reflected intuitive or creative attempts to address
      perceived pathologic issues such as sphincter disease, calculi, and fibrotic
      masses. The past and present remain a confusion of etiologies and diagnoses.
      Treatment remains for the most part a dramatically disappointing scenario, and
      both patients and their physicians are frustrated. Although the remarkable
      technologic progress exhibited by the odyssey of operative strategy from simple
      drainage, to ductal drainage, to the complex refinements of extensive resection
      is a testimonial to surgical skill and determination, it has been nullified to a
      large extent by the inability to address the initiating factors of the disease or
      alter those that engender progress of the pathology. It is not unreasonable to
      recognize that we are facing an enigmatic disease process generically classified
      as "chronic pancreatitis" for want of any more specific terminology. In the light
      of our current knowledge and experience, intervention should probably be modest
      in the extreme and limited to centers and individuals with expertise or who are
      involved in specific studies to determine the precise criteria and techniques
      necessary for optimum intervention. It is important that when charting such a
      course future surgeons involved in the management of chronic pancreatitis have an
      understanding of the historical evolution of the subject. As Theodor Billroth,
      the greatest of the surgical innovators remarked: "An awareness of the past is
      necessary to comprehend the present, and without it no consideration of the
      future is possible."

PMID- 12209235
TI  - Anatomic resection for severe liver trauma.

PMID- 12209236
TI  - Consistent decrease in telomere length in parathyroid tumors but alteration in
      telomerase activity limited to malignancies: preliminary report.
AB  - Telomerase is known to be activated and telomere length altered in various types
      of malignant and benign tumors, but whether this is also the case for parathyroid
      lesions has hitherto been unclear. We therefore investigated telomerase activity
      and telomere length in 3 parathyroid metastatic cancers, 6 adenomas, 2 cases of
      parathyroid hyperplasia, and 16 samples of normal parathyroid tissue. Telomerase
      activity, assayed by the telomeric repeat amplification protocol, was detected in
      all of the parathyroid cancers (100%), in none of the 8 parathyroid benign
      lesions, and in only 1 of the 16 normal parathyroid samples (8.3%). Telomere
      length, determined by the terminal restriction fragment assay, was reduced in the
      tumor tissues with a mean telomere length of 8.23 +/- 0.86 kbp compared with the
      12.61 +/- 0.81 kbp for the 16 age-matched subjects (p = 0.002). The results
      indicate that telomerase activity and telomere length may reflect the biologic
      behavior of individual parathyroid lesions.

PMID- 12209237
TI  - Indications and complications of latissimus dorsi myocutaneous flaps in oncologic
      breast surgery.
AB  - The use of the latissimus dorsi myocutaneous flap (LDMF) in reconstructive breast
      surgery is well documented. Few reports exist of its use in oncologic breast
      surgery. This series describes indications and complications of the LDMF in
      locally advanced cancer. The records of 83 patients were analysed for age and
      sex, menstrual status, stage, indication, margins of resection, chemotherapy,
      radiotherapy, complications, and survival. The indication was to cover defects
      caused by resection of locally advanced breast cancer (67 cases), recurrent
      breast cancer (13 cases), radiation damage (2 cases), and surgical complications
      (1 case). The mean age of the patients was 50.2 years; 52% were postmenopausal.
      The flaps had mean diameters of 32 by 14 cm. The donor site was skin grafted.
      Clear margins were achieved in 83%. At the LDMF insertion site, wound infection
      required drainage in 1 case; flap necrosis required reintervention in 7 cases. In
      2 cases a second skin graft was done for the LDMF donor site. The proportions of
      wound infections and incomplete skin graft take were significantly greater in
      patients receiving preoperative cyclophosphamide/methotrexate/5-fluorouracil
      (CMF) versus cyclophosphamide/doxorubicin/5-fluorouracil (CAF) chemotherapy (p <
      0.001 and p < 0.05, respectively). The late complication rate was 7.2%. The mean
      follow-up is 40.0 months. The complication rates for CMF versus CAF chemotherapy
      suggest an adverse effect of methotrexate, which warrants further investigation.
      The use of the LDMF made wide resection of locally advanced lesions and
      radionecrosis possible; major complications were rare. LDMF has its place in the
      armamentarium of the surgeon who regularly sees locally advanced breast cancer.

PMID- 12209238
TI  - Minimal blood loss in patients undergoing radical retropubic prostatectomy.
AB  - The objective of this study was to evaluate blood loss in patients undergoing
      radical retropubic prostatectomy. Blood loss and operating time were evaluated in
      a series of 197 consecutive patients with prostate cancer who underwent radical
      retropubic prostatectomy by a two-surgeon team. The patients were positioned
      supine with the table flexed and the patient in about 35 degrees Trendelenburg
      position. Results were compared with those recorded for an earlier series of 40
      patients operated in the supine position alone. The influence of parameters that
      might affect blood loss (peridural and hypotensive anesthesia, bilateral
      hypogastric artery clamping) was assessed in multivariate analyses. Since
      adoption of a Trendelenburg position with flexion of the hips, the mean
      intraoperative blood loss has decreased by 80%, to a low level of 260 cc; and
      transfusions have become exceptional (0.5%). The decrease in blood loss
      correlated with a decrease in operating time, which was reduced to an average of
      90 minutes. Whereas epidural anesthesia decreased blood loss by a modest 27%,
      intraoperative blood pressure, bilateral hypogastric artery clamping, and nerve
      sparing had little or no significant effect. Patient position and the surgical
      skill of a two-man team can virtually eliminate the risk of blood loss during
      radical retropubic prostatectomy. There is thus no need always to resort to other
      procedures or to preoperative autologous blood donation.

PMID- 12209239
TI  - One hundred citation classics in general surgical journals.
AB  - The number of times an article is cited in scientific journals reflects its
      impact on a specific biomedical field or specialty and reflects the impact of the
      authors' creativity. Our objective was to identify and analyze the
      characteristics of the 100 most frequently cited articles published in journals
      dedicated to general surgery and its close subspecialties. Using the database
      (1945-1995) of the Science Citation Index of the Institute for Scientific
      Information, 1500 articles cited 100 times and more were identified and the top
      100 articles selected for further analysis. The 100 articles were published
      between 1931 and 1990, with more than two-thirds of them published after 1960.
      The mean number of citations per article was 405, (range 278-1013). Altogether,
      84 of the articles originated from North America (USA 78, Canada 6) and the UK
      (12). New York State led the list of U.S. states with 14, and Harvard and
      Columbia University led the list of institutions with 6 articles each. The 100
      articles were published in 10 surgical journals led by the Annals of Surgery (n =
      40), followed by Surgery (n = 15), Archives of Surgery (n = 12), Surgery,
      Gynecology and Obstetrics (n = 11), and British Journal of Surgery (n = 10). A
      total of 80 of the articles reported clinical experiences, 6 were clinical review
      articles, and 14 dealt with basic science. Eighteen articles reported a new
      surgical technique and six a prosthetic device. Gastrointestinal surgery and
      trauma and critical care led the list of the surgical fields, each with 25
      articles, followed by vascular surgery (n = 15). Thirty-four persons authored two
      or more of the top-cited articles. This list of the top-cited papers identifies
      seminal contributions and their originators, facilitating the understanding and
      discourse of modern surgical history and offering surgeons hints about what makes
      a contribution a "top-cited classic." To produce such a "classic" the surgeon and
      his or her group must come up with a clinical or nonclinical innovation,
      observation, or discovery that has a long-standing effect on the way we practice
      be it operative or nonoperative. Based on our findings, to be well cited such a
      contribution should be published in the English language in a high-impact
      journal. Moreover, it is more likely to resonant loudly if it originates from a
      North American or British "ivory tower."

PMID- 12209240
TI  - Contemporary outcomes of ambulatory laparoscopic cholecystectomy in a major
      teaching hospital.
AB  - Ambulatory laparoscopic cholecystectomy is an established practice in our
      institution, with an experience of more than 800 cases. The present study is
      conducted to evaluate the contemporary outcomes of day-case laparoscopic
      cholecystectomy in the setting of a major teaching hospital. A retrospective
      analysis of 200 patients who underwent ambulatory laparoscopic cholecystectomies
      was performed to evaluate the postoperative morbidity, unplanned admission, and
      readmission rates. Causes for unanticipated admission and readmission were
      analyzed. Uneventful recovery was attained in 185 (92.5%) patients. The mean
      length of the operation was 56 +/- 20 (SD) minutes. There was no hospital
      mortality, and no patient required conversion to open cholecystectomy. Nine
      patients were admitted overnight after operation because of nausea and vomiting
      (n = 3), pain (n = 2), urinary retention (n = 2), medical observation n = 1), and
      patient's preference (n = 1), leading to an unanticipated admission rate of 4.5%.
      Six patients required readmission because of postoperative complications (n = 4)
      and abdominal pain (n = 2), giving a readmission rate of 3%. The overall
      postoperative morbidity rate was 3% (n = 6), including retained stones n = 4),
      bile leakage (n = 1), and hepatic subcapsular hematoma (n = 1). Ambulatory
      laparoscopic cholecystectomy is a safe practice in appropriately selected
      patients. Postoperative nausea and vomiting was the commonest reason for
      unanticipated admission after operation, and retained stones was the most
      frequent postoperative morbidity necessitating readmission.

PMID- 12209241
TI  - Mode of infiltrative growth of colorectal liver metastases is a useful predictor
      of recurrence after hepatic resection.
AB  - Many studies have been conducted to determine prognosis on the basis of the
      characteristics of metastatic liver tumor from colorectal cancer. The present
      study was carried out to determine whether the pathological mode of infiltrative
      growth (INF) of a metastatic liver nodule is useful in predicting recurrence in
      the remnant liver after hepatic resection. A total of 42 curative hepatic
      resections were performed for 37 patients with isolated liver metastases from
      colorectal cancer. Multivariate analysis (n = 42) showed that number, INF type,
      and size of liver metastases were statistically significant as independent risk
      factors. Of these, 28 resected liver metastases (smaller than 6 cm in size or
      containing fewer than 4 nodules) were classified pathologically into INF alpha or
      beta types (INF a b; n = 14) and gamma type (INFg; n = 14). Disease-free survival
      at 5 years was 64% for patients with INF a b type, and 14% for those with the INF
      g type of liver metastases. Of these, recurrent disease of the liver after
      hepatic resection was found in 2 (14%) and 11 (79%) patients with INF a b and INF
      g types, respectively. From these observations, we concluded that pathological
      infiltrative growth of liver metastases is an informative predictor of disease
      free survival and especially of recurrence in the remnant liver.

PMID- 12209242
TI  - Liver surgery in the era of tissue-preserving resections: early and late outcome
      in patients with primary and secondary hepatic tumors.
AB  - During recent decades, the understanding of the segmental-oriented liver anatomy
      has enabled development of resection of isolated liver segments or sectors as
      dictated by the localization and extent of the mass lesion. These newer surgical
      procedures provide the advantage of maximal preservation of functional
      parenchyma, therefore minimizing the occurrence of postoperative liver failure
      and, at the same time, expanding the indications for surgery. We analyzed the
      results after classical hemihepatectomies and segment-based resections in a
      consecutive, nonselected patient group. During the 7-year period between November
      1993 and November 2000, 270 patients with primary or secondary liver tumors were
      treated in our hospital; 167 of these patients underwent curative resections and
      their relevant data were entered into a statistical database. There were 77
      classical hemihepatectomies and 90 tissue-preserving resections. Total mortality
      and morbidity for the series was 3.6% and 29.9%, respectively. Morbidity but not
      mortality was significantly lower after tissue-preserving resections than after
      classical hemihepatectomy. Median follow-up was 36 months. Survival was
      comparable for the two different surgical approaches for patients with secondary
      liver malignancies. In contrast, patients with hepatocellular carcinomas lived
      significantly longer after tissue-preserving resections. Tissue-preserving liver
      resection is a safe technique allowing maximal preservation of functional
      parenchyma without compromising radicality. Therefore, tissue-preserving
      resection is especially useful for patients with hepatocellular carcinomas and
      cirrhosis.

PMID- 12209243
TI  - Pedunculated hepatocellular carcinoma: clinicopathologic study of 18 surgically
      resected cases.
AB  - We present the clinical features and outcomes of 18 surgically treated
      pedunculated hepatocellular carcinomas (P-HCCs). Hepatocellular carcinoma is a
      notorious, hyperendemic disease in Taiwan. Pedunculated HCC, although not a novel
      finding, has been recognized and diagnosed early by various imaging modalities.
      However, the clinicopathologic picture has not been fully clarified, and the
      prognosis varies in each report. From 1986 to 1998 the clinical features of 18
      surgically treated cases of P-HCC were reviewed, including demographics,
      laboratory data, operative findings, pathologic features, and follow-up results.
      Factors that may influence the outcomes were also analyzed. Clinical features and
      outcomes of 414 patients with nonpedunculated hepatocellular (HCC) were
      summarized for comparison. Of 432 surgical resected hepatocellular carcinomas, 18
      (4.2%) were P-HCCs. Larger tumor size, more capsule formation, less vascular
      invasion, and wider resection margins were significantly prominent in the
      patients in P-HCC group compared with those in the NP-HCC group. Multivariate
      stepwise logistic regression analysis revealed that the P-HCC group had
      significantly larger tumors and wider resection margins. The 1-, 3-, and 5-year
      survival rates of P-HCC patients were 88.3%, 77.4%, and 45.6%, respectively. A
      significant difference in survival was found between the P-HCC and NP-HCC groups.
      P-HCC patients without vascular invasion might have a significantly better
      survival demonstrated by log-rank analysis stratified by capsular invasion,
      vascular invasion, resection, and tumor size. We present the clinical features
      and outcomes of 18 surgically treated pedunculated HCCs. Pedunculated HCCs might
      have a better survival than conventional HCCs after hepatic resection, especially
      if there is no vascular invasion.

PMID- 12209244
TI  - Gastrointestinal recovery and outcome after laparoscopy-assisted versus
      conventional open distal gastrectomy for early gastric cancer.
AB  - Laparoscopy-assisted gastrectomy has been increasingly reported as the treatment
      of choice for early gastric cancer. However, there is little information
      regarding the benefits of laparoscopy-assisted distal gastrectomy (LADG). LADG
      and conventional open distal gastrectomy (DG) for early gastric cancer were
      compared in terms of operative outcome, recovery of bowel function,
      complications, and changes in body weight. Thirty-four patients underwent LADG
      for early gastric cancer. These patients were compared with 31 patients who
      underwent DG during the same period. For estimating gastrointestinal motility
      recovery, 20 radiopaque markers were inserted into the duodenum during surgery,
      and abdominal X-rays were taken daily until all markers were seen in the
      ascending colon. Age, gender, and histologic differentiation of the lesions were
      matched. The LADG group required a significantly longer operative time and the
      dissection of fewer lymph nodes. Postoperative hospital stay and the occurrence
      of postoperative complications (ileus) were significantly shorter and less
      frequent in the LADG group. The LADG group showed a more rapid recovery of
      gastrointestinal motor function compared with the DG group during the early
      postoperative period. Body weight 24 months after LADG was about 100% of pre
      illness weight, but no further weight change was encountered in the DG group. For
      selected patients with early gastric cancer, LADG with lymphadenectomy can
      provide a rapid recovery and good quality of life without compromising the cure
      rate.

PMID- 12209245
TI  - Clinical outcome of proximal versus total gastrectomy for proximal gastric
      cancer.
AB  - Tumors in the upper one-third of the stomach has been increasing. Although the
      standard operation for proximal gastric cancer has been total gastrectomy, some
      have used proximal gastrectomy reconstructed by jejunum or gastric tube. The aim
      of this study was to evaluate the surgical results, hospital costs, and quality
      of life after gastrectomy for cancer. A consecutive series of 51 patients with
      stage I or II proximal gastric cancer was studied: 14 underwent proximal
      gastrectomy reconstructed by gastric tube (direct anastomosis between esophagus
      and remnant of tube-like stomach), 17 proximal gastrectomy reconstructed by
      jejunum, and 20 total gastrectomy in Roux-en-Y fashion. Quality of life was
      estimated by a 24-item questionnaire with a scoring system of 1 to 3, and
      hospital costs covered all charges during the hospital stay. Operating time,
      blood loss, and hospital stay for the gastric tube group were less than those for
      the jejunum group or the total gastrectomy group. Hospital charges for the
      gastric tube group were lower than those for the jejunum group or the total
      gastrectomy group (141 x 10 4 yen, 179 x 10 4 yen, 211 x 10 4 yen, respectively).
      Although the total score for quality of life was not significantly different
      among the three groups (35.9, 39.5, 37.6), the number of meals per day was less
      and the performance status was better in the gastric tube group. Jejunal
      interposition was less favorably accepted by the patients as a good operation
      they would recommend to others. The results indicate that, in patients with
      proximal gastric cancer, proximal gastrectomy reconstructed by gastric tube
      provides a shorter operating time, earlier recovery, lower hospital charge, and
      better performance status when compared with proximal gastrectomy reconstructed
      with jejunum or total gastrectomy.

PMID- 12209246
TI  - Neoadjuvant chemotherapy followed by salvage surgery: effect on survival of
      patients with primary noncurative gastric cancer.
AB  - The prognosis for gastric cancer patients who undergo noncurative resection is
      extremely poor. This study evaluated the effects of neoadjuvant chemotherapy for
      primary noncurative gastric cancer. Thirty-four patients with biopsy-proven
      noncurative gastric cancer were treated with either of two neoadjuvant
      chemotherapies: FEMTXP (5-fluorouracil, epirubicin, methotrexate, cisplatin) or
      THP-FLPM (pirarubicin, 5-fluorouracil, leucovorin, cisplatin, mitomycin C).
      Noncurability was determined by conventional staging procedures, staging
      laparoscopy, and exploratory laparotomy. After chemotherapy the resectability of
      the tumors was reassessed. Patients who were judged to be candidates for curative
      resection underwent salvage surgery. Of the final 33 patients, 8 (24.2%) showed a
      major response [0 complete response (CR), 8 partial response (PR)]. In three
      patients the second laparoscopy revealed disappearance of the peritoneal
      metastasis. Of the 33 patients, 14 (42.4%) underwent salvage surgery, including 8
      curative resections (2 curability A, 6 curability B). Pathologic examinations
      revealed a grade 2 response in eight patients but no grade 3 response. Univariate
      analysis showed the following to be significant prognostic factors: histology
      type (differentiated type vs. undifferentiated type; p = 0.035), T4 as a
      noncurative factor (T4 vs. T3 or less; p = 0.025), clinical response (PR + no
      change vs. progressive disease; p = 0.002), and salvage surgery (resected vs.
      unresected; p = 0.001). Among these factors, salvage surgery was found to be the
      only independent prognostic factor by multivariate analysis, with a relative risk
      of 0.253 and a 95% confidence interval of 0.066 to 0.974. The treatment was well
      tolerated. Major toxicities of WHO grade 3 or more were leukopenia in 20 (60.6%),
      gastrointestinal toxicities in 5 (15.2%), renal toxicities in 2 (6.1%), and
      alopecia in 1 (3.0%). In conclusion, neoadjuvant chemotherapy is effective for
      primary noncurative gastric cancer when salvage surgery can be performed. A
      chemotherapy regimen with a higher complete response rate would improve the
      prognosis of this dismal disease even more.

PMID- 12209247
TI  - Different patterns of recurrence in gastric cancer depending on Lauren's
      histological type: longitudinal study.
AB  - The aim of this multicenter longitudinal study was to evaluate the pattern of
      recurrence in patients submitted to potentially curative surgery for intestinal
      type and diffuse-type gastric cancer. The study included 412 patients surgically
      treated at three Italian surgical departments, subdivided into 273 intestinal
      type cases (group A) and 139 diffuse-type cases (group B). Recurrence of disease
      was found in 41% of group A cases and 65% of group B cases (p < 0.0001). The
      incidence of locoregional, hematogenous, and peritoneal recurrence was 20%, 19%,
      and 9% in group A, and 27%, 16%, and 34% in group B, respectively; the difference
      between the two groups was statistically significant for peritoneal recurrence (p
      < 0.0001). Multivariate analysis identified as prognostic variables lymph node
      status, depth of invasion, extent of lymphadenectomy, advanced age, and male
      gender in group A; depth of invasion, extent of lymphadenectomy, tumor size, and
      lymph node status, in group B. Whereas in group A the incidence of peritoneal
      recurrence was limited in all subgroups examined, in group B very high rates were
      observed in cases with infiltration of the serosa, involvement of second-level
      lymph nodes, or large tumor size. The notable difference in the risk of
      peritoneal recurrence between the intestinal and diffuse types should be taken
      into consideration in the therapeutic approach to gastric cancer.

PMID- 12209248
TI  - Long-term results of patients with pT2 rectal cancer treated with radiotherapy
      and transanal endoscopic microsurgical excision.
AB  - Anterior resection and abdomino-perineal resection are the surgical techniques
      used most frequently in the treatment of rectal cancer. Local recurrence rates of
      10% to 14% are described after these conventional procedures. Preoperative
      neoadjuvant radiotherapy reduces local failure. Because local excision techniques
      can be applied to treat early rectal cancer in selected patients, we evaluated
      the results of preoperative high-dose radiotherapy and transanal endoscopic
      microsurgical excision (TEM) in patients with T2 rectal cancer. All patients
      underwent preoperative irradiation with 5,040 cGy, divided over 5 weeks. Forty
      days after completion of radiotherapy, the patients underwent complete full
      thickness local excision of the rectal lesion including adjacent perirectal fat
      by TEM. The patients were followed for up to 8 years. Thirty-five patients, with
      pT2 rectal cancer as determined by pathological examination of the surgical
      specimen were enrolled in the present study. The tumors were responsive to
      preoperative radiotherapy in 82.8% of cases. No intraoperative complications and
      no conversion to open surgery were observed. No major complications and no
      mortality occurred during the 60-day postoperative period. Minor postoperative
      complications were observed in 5 patients (14.3%). The median follow-up of the
      patients was 38 months (range 24 to 96 months). One local recurrence (2.85%) was
      noted. The probability of surviving at 96 months after completion of treatment
      was 83%. Local excision by TEM combined with preoperative high-dose radiotherapy
      can achieve results similar to those observed after conventional surgery in
      patients with pT2 rectal cancer.

PMID- 12209251
TI  - Ectoenzymatic ratios in relation to particulate organic matter distribution (Ross
      Sea, Antarctica).
AB  - The results of a study on ectoenzymatic activity (the enzyme activity bound to
      particles larger than 0.2 micro m) and its relation to organic particle
      concentration are reported here. The sampling was carried out during the 1994
      Antarctic spring, at a fixed station (Station 11) in the polynya of the Ross Sea,
      an area characterized by quick changes in sea ice cover. The sampling was
      repeated 4 times over a 20-day time period. The particulate organic matter
      distribution followed the physical structure of the water column, which depends
      on ice dynamics and is mainly determined by salinity. In the mixed-water surface
      layer (0-50 m) the concentrations were higher (on average 65.6 micro gC/L) than
      in the deeper water layer (50 m-bottom) (on average 19.1 micro gC/L). This
      distribution and quality, expressed by the protein:carbohydrate ratio, linked the
      particulate organic matter to the phytoplanktonic bloom which was in progress in
      the area. We determined the kinetic parameters of the glycolytic and proteolytic
      ectoenzymes and also the total activity for the proteolytic enzyme, in order to
      evaluate the contribution of the particle-bound activity. We observed higher
      values in the surface layer than in the deeper layer. b-Glucosidase activity
      ranged between 0.03 and 0.92 nmol L(-1) h(-1); b-N-acetylglucosaminidase activity
      was in the range of 0.04-0.58 nmol (L-1) (h-1). The total proteolytic activity
      (leucine aminopeptidase) ranged between 0.85 and 33.71 nmol L(-1) (h-1). The
      ectoproteolytic activity was about 35-60% of the total. The Km values were
      slightly higher for the proteolytic activity (on average 0.43 micro M for
      ectoproteolytic activity and 0.58 micro M for total proteolytic activity) than
      for the b-glucosidase (on average 0.36 micro M) and b-N-acetylglucosaminidase (on
      average 0.17 micro M), showing no remarkable variations in the water column. The
      ectoenzymatic ratios and their relationship with particulate organic substrates
      confirm the close link between organic substrate availability and degradation
      system response. The significant and positive correlations are not specific and
      suggest a prompt and efficient systemic response to the input of trophic
      resources. Nevertheless, changes in ectoenzyme activity and synthesis may act as
      adaptive responses to changing features of the ecosystem. In particular,
      variations in the proteolysis:glycolysis ratio depend on the functional features
      of the ecological system. In our study area this ratio is higher (about 10 or
      more) during production (particularly autotrophic) and lower (about 5 or less)
      during degradation/consumption events. The analysis of previous data, collected
      over a larger area characterized by different environmental conditions due to the
      changes of the pack ice cover, during the same cruise, confirms the existence of
      a significant relationship. Furthermore, the analysis of enzyme-uptake systems,
      expressed as Vmax:Km ratio, suggests that glycolytic ectoenzymes, although poorly
      expressed, may encourage microconsumers to grow rapidly on a wide range of
      organic substrates, including the refractory ones such as cellulose and chitin.
      However, low ectoenzyme potential exploitation rates of available organic
      substrates (on average about 5% for glycolytic and 12% for proteolytic
      ectoenzymes) would suggest that, during spring, zooplankton grazing or vertical
      and lateral transport are likely to play an important role in the removal of
      organic materials from the system.

PMID- 12209252
TI  - Diversity of azospirillum strains isolated from rice plants grown in saline and
      nonsaline sites of coastal agricultural ecosystem.
AB  - The diversity of indigenous Azospirillum spp. associated with rice cultivated
      along the coastline of Tamil Nadu was analyzed. Twelve sites with varying soil
      characteristics such as salinity, texture, and the host variety were chosen. Of
      the 402 strains isolated using NFB media, 302 were confirmed to be Azospirillum
      spp. and subjected to DNA polymorphism analysis using PCR-RFLP of 16S rDNA. They
      were also screened for their salt tolerance and microaerobic N2-fixing-dependent
      growth. On species identification, all the strains were found to be A.
      brasilense, A. lipoferum, or unidentified. On comparing the influence of the
      previously noted variability on the indigenous population, soil salinity was
      found to play a dominant role. This was revealed by PCR-RFLP studies and salt
      tolerance studies. A high association between soil salinity and the distribution
      of Azospirillum genotypes reveals that soil salinity should be taken into
      consideration while developing biofertilizers specifically for the coastal
      agricultural ecosystem.

PMID- 12209253
TI  - Phylogenetic diversity of winter bacterioplankton of eutrophic siberian
      reservoirs as revealed by 16S rRNA gene sequence.
AB  - Using 16S rRNA gene sequence analyses we investigated the bacterial diversity of
      winter bacterioplankton of two eutrophic Siberian reservoirs. These reservoirs
      show similarity in phytoplankton community composition in spring and autumn but
      tend to differ in summer in exhibiting cyanobacterial bloom. Forty-eight unique
      partial 16S RNA gene sequences retrieved from two libraries were mostly
      affiliated with the class Actinobacteria, b subdivision of the class
      Proteobacteria, and the phylum Cytophaga-Flavobacterium-Bacteroides. The clone
      library of the pond exhibiting summer cyanobacterial bloom showed more diversity
      in sequence composition. A significant number of bacterial 16S rRNA gene clones
      were closely related to freshwater bacteria previously found in different aquatic
      ecosystems. This finding confirms the assumption that some bacterial clades are
      globally distributed.

PMID- 12209254
TI  - Dissolved primary production and the strength of phytoplankton- bacterioplankton
      coupling in contrasting marine regions.
AB  - We analyzed the strength of phytoplankton-bacterioplankton coupling by comparing
      the rate of particulate (PPP) and dissolved primary production (DPP) with
      bacterial carbon demand (BCD) in four contrasting marine regions: offshore and
      coastal waters of the Southern Ocean, a coastal area of the NE Atlantic, and a
      coastal-offshore transect in the NW Mediterranean. We measured bacterial
      heterotrophic production (BHP) and estimated BCD from a literature model. Average
      phytoplanktonic percent extracellular release [PER = DPP/(DPP + PPP)] was 18-20%
      in the Antarctic (offshore and coastal, respectively), 16% in the NW
      Mediterranean, and 7% in the NE Atlantic. A significant inverse relationship was
      found between PER and total system productivity with pooled data. On average BHP
      amounted to <5% of total primary production in all regions. However, the strength
      of phytoplankton-bacterioplankton coupling, estimated as the potential importance
      of DPP in meeting BCD, differed greatly in the four regions. DPP was highly
      correlated to BCD in offshore Antarctic waters and was sufficient to meet BCD. In
      contrast, BCD exceeded DPP and bore no significant relationship in the remaining
      regions. The data suggest that a strong dependence of bacteria on algal
      extracellular production is only expected in open-ocean environments isolated
      from coastal inputs of DOC.

PMID- 12209255
TI  - Bacterial community dynamics across a floristic gradient in a temperate upland
      grassland ecosystem.
AB  - Alterations in soil bacterial communities across a transect between a semi
      natural upland grassland and an agriculturally improved enclosure were assessed
      using culture-based methods and a nucleic-acid-based method, terminal restriction
      fragment length polymorphism (TRFLP). While plant diversity decreased across the
      transect towards the improved area, numbers of 16S rDNA terminal restriction
      fragments increased, indicating an increase in numbers of bacterial ribotypes.
      Bacterial numbers, microbial activity, and potential functional diversity also
      followed a similar trend, increasing with decreasing plant diversity. Alterations
      in bacterial community structure were coincident with changes in soil
      physicochemical properties which also changed across the transect. Increases in
      soil pH, nitrate, phosphorus, potassium, and calcium occurred toward the improved
      grassland, while organic matter and ammonium declined. The inverse relationship
      between floristic diversity and bacterial ribotype numbers suggests that soil
      physicochemical factors may be as influential in determining bacterial diversity
      in soils of upland grassland communities as floristic diversity.

PMID- 12209257
TI  - Molecular biology and biochemistry of ammonia oxidation by Nitrosomonas europaea.
AB  - Nitrosomonas europaea uses only NH(3), CO(2) and mineral salts for growth and as
      such it is an obligate chemo-lithoautotroph. The oxidation of NH(3) is a two-step
      process catalyzed by ammonia monooxygenase (AMO) and hydroxylamine oxidoreductase
      (HAO). AMO catalyzes the oxidation of NH(3) to NH(2)OH and HAO catalyzes the
      oxidation of NH(2)OH to NO(2)(-). AMO is a membrane-bound enzyme composed of
      three subunits. HAO is located in the periplasm and is a homotrimer with each
      subunit containing eight c-type hemes. The electron flow from HAO is channeled
      through cytochrome c(554) to cytochrome c(m552), where it is partitioned for
      further utilization. Among the ammonia-oxidizing bacteria, the genes for AMO,
      these cytochromes, and HAO are present in up to three highly similar copies.
      Mutants with mutations in the copies of amoCAB and hao in N. europaea have been
      isolated. All of the amoCAB and hao gene copies are functional. N. europaea was
      selected by the United States Department of Energy for a whole-genome sequencing
      project. In this article, we review recent research on the molecular biology and
      biochemistry of NH(3) oxidation in nitrifiers.

PMID- 12209256
TI  - Cofactor-dependent pathways of formaldehyde oxidation in methylotrophic bacteria.
AB  - Methylotrophic bacteria can grow on a number of substrates as energy source with
      only one carbon atom, such as methanol, methane, methylamine, and
      dichloromethane. These compounds are metabolized via the cytotoxin formaldehyde.
      The formaldehyde consumption pathways, especially the pathways for the oxidation
      of formaldehyde to CO(2) for energy metabolism, are a central and critical part
      of the metabolism of these aerobic bacteria. Principally, two main types of
      pathways for the conversion of formaldehyde to CO(2) have been described: (1) a
      cyclic pathway initiated by the condensation of formaldehyde with ribulose
      monophosphate, and (2) distinct linear pathways that involve a dye-linked
      formaldehyde dehydrogenase or C(1) unit conversion bound to the cofactors
      tetrahydrofolate (H(4)F), tetrahydromethanopterin (H(4)MPT), glutathione (GSH),
      or mycothiol (MySH). The pathways involving the four cofactors have in common the
      following sequence of events: the spontaneous or enzyme-catalyzed condensation of
      formaldehyde and the respective C(1) carrier, the oxidation of the cofactor-bound
      C(1) unit and its conversion to formate, and the oxidation of formate to CO(2).
      However, the H(4)MPT pathway is more complex and involves intermediates that were
      previously known solely from the energy metabolism of methanogenic archaea. The
      occurrence of the different formaldehyde oxidation pathways is not uniform among
      different methylotrophic bacteria. The pathways are in part also used by other
      organisms to provide C(1) units for biosynthetic reactions (e.g., H(4)F-dependent
      enzymes) or detoxification of formaldehyde (e.g., GSH-dependent enzymes).

PMID- 12209258
TI  - Characterization of Synechocystis sp. strain PCC 6803 and deltanbl mutants under
      nitrogen-deficient conditions.
AB  - The impact of nitrogen deficiency on the unicellular cyanobacterium Synechocystis
      sp. strain PCC 6803 and three nbl (non-bleaching) mutants (deltanblA1, deltanblA2
      and deltanblB) was investigated. The deltanblA mutants entered a non-dividing,
      dormant state soon after the initiation of nitrogen starvation. The cells became
      larger, the membrane system was disorganized, and ribosomes were found near the
      membranes much less frequently. Photosystem II (PSII) activity declined to
      approximately 10% of the wild-type level and the amount of D1 protein declined
      precipitously, despite adequate psbA transcription; PSI activity declined, but
      more slowly. Transcription from PSII (except psbA), PSI and phycobilisome genes
      was very low. Fluorescence at 77K indicated many partially assembled or
      unassembled phycobilisomes. The level of transcript accumulation increased to
      normal by 4 h after the readdition of nitrogen to the culture. When NblA was
      present, the phycobilisomes were degraded to provide a nitrogen source for
      continued growth and metabolism. An important difference between the wild-type,
      mutant deltanblB, and the deltanblA mutants was seen in the rod linker proteins.
      Under nitrogen-deprivation condition, the L(R)33 and L(R)34.5 linker proteins
      were extensively degraded in the wild-type and deltanblB mutant, but remained
      intact in the deltanblA mutants.

PMID- 12209259
TI  - Enniatin synthetase is a monomer with extended structure: evidence for an
      intramolecular reaction mechanism.
AB  - Enniatin synthetase (Esyn), a 347-kDa multienzyme consisting of two substrate
      activation modules, is responsible for the nonribosomal formation of the
      cyclohexadepsipeptide enniatin. The synthesis follows the so-called thiol
      template mechanism. While this process is basically well established, no
      substantial insight into the 3-dimensional arrangement of these enzymes and
      possible interactions between them exists to date. To find out whether enniatin
      synthesis is an intramolecular process or the result of three interacting Esyn
      molecules (intermolecular), analytical ultracentrifugation equilibration studies
      were carried out. The molecular mass of Esyn was determined by
      ultracentrifugation and is in good agreement with that calculated from the ORF of
      the encoding gene, indicating that Esyn exists in solution as a monomer. This
      strongly suggests that synthesis of the cyclohexadepsipeptide enniatin follows an
      intramolecular reaction mechanism in which all three reaction cycles are
      catalyzed by a single Esyn molecule. This finding was supported by in vitro
      complementation studies in which [(14)C]-methylvalyl Esyn, upon incubation with
      the second substrate D-2-hydroxyisovaleric acid (D-Hiv) and ATP, did not yield
      radioactive enniatin. This confirms our previous assumption of an iterative
      reaction mechanism similar to that for fatty acid synthase. Furthermore, the
      sedimentation rate constant evaluated from analytical ultracentrifugation was
      lower (S(20,w)=14.1S) than expected (S(20,w)=16.9S) for a globular protein,
      indicating that Esyn has an extended structure.

PMID- 12209260
TI  - Formation of methylantimony species by an aerobic prokaryote: Flavobacterium sp.
AB  - Pure cultures of an aerobically grown Flavobacterium sp. were shown by hydride
      generation-cold trap-atomic absorption spectrometry to biomethylate inorganic
      antimony (III) supplied as potassium antimony tartrate. Growth inhibition of the
      Flavobacterium sp. by antimony (III) over the range 0-30 mg Sb l(-1) was assessed
      by optimising parameters within an extended logistic growth model. Antimony (III)
      concentrations over this range influenced both the extent of antimony
      biomethylation (up to 4.0 microg l(-1)) and the relative proportions of the
      involatile mono-, di, and trimethylantimony species formed. Provision of
      inorganic arsenic (III) alongside antimony (III) enhanced formation of the
      involatile methylantimony species up to eight-fold. The data are consistent with
      accumulation of involatile intermediates from an antimony or arsenic
      biomethylation pathway in culture supernatants. Low yields of methylantimony
      species (<0.03%) suggest that antimony biomethylation by the Flavobacterium sp.
      was a fortuitous rather than a primary resistance mechanism for this element.
      These findings demonstrate that anaerobiosis is not an obligate requirement for
      methylantimony formation in prokaryotes, thus broadening the range of habitats
      for potential formation of methylantimony species in nature.

PMID- 12209261
TI  - Aerobic and anaerobic metabolism of squalene by a denitrifying bacterium isolated
      from marine sediment.
AB  - The aerobic and anaerobic metabolism of the isoprenoid alkene squalene was
      investigated in a new type of marine denitrifying bacterium, strain 2sq31,
      isolated from marine sediment. Strain 2sq31 was identified as a species of
      Marinobacter. Under denitrifying conditions, the strain efficiently degraded
      squalene; of 0.7 mmol added per liter of medium, 77% was degraded within 120 days
      under anoxic conditions with nitrate as electron acceptor. Tertiary diols and
      methyl ketones were identified as metabolites, and an anaerobic pathway was
      suggested to explain the formation of such compounds. The first step in anaerobic
      degradation of squalene by strain 2sq31 involves hydration of double bonds to
      tertiary alcohols. Under oxic conditions, the degradation of squalene by strain
      2sq31 was rapid and involved oxidative splitting of the C-10/C-11 or C-14/C-15
      double bonds, in addition to the pathways observed under denitrifying conditions.

PMID- 12209262
TI  - Analysis of the initiator tRNA genes from a slow- and a fast-growing
      Mycobacterium.
AB  - Initiation of protein synthesis is a major post-transcriptional regulatory step
      in gene expression. The initiator tRNA gene from Mycobacterium smegmatis, a fast
      growing mycobacterium, was characterized and compared with its counterpart from
      Mycobacterium tuberculosis, a slow-growing mycobacterium. In both mycobacteria,
      the functional initiator tRNA genes were found in a single copy. Unlike the M.
      tuberculosis initiator tRNA, the CCA end of the M. smegmatis initiator is not
      encoded in the gene, and it is most likely added post-transcriptionally.
      Transcription start site mapping allowed accurate assignment of the hexameric -10
      and -35 promoter elements for both genes. These elements of the M. smegmatis
      initiator tRNA gene contain single nucleotide changes compared to their
      respective counterparts in the M. tuberculosis gene. Chloramphenicol acetyl
      transferase reporter assays suggested that the promoter of the initiator tRNA
      gene from M. smegmatis is twice as strong as that of M. tuberculosis,
      irrespective of whether the assays were performed in the fast-growing homologous
      host (M. smegmatis) or the slow-growing heterologous host (M. tuberculosis).
      Characterization of the M. smegmatis metU promoter, in this study, provides a
      valuable tool for the expression of genes in mycobacteria.

PMID- 12209263
TI  - Identification of cofactor discrimination sites in NAD-isocitrate dehydrogenase
      from Pyrococcus furiosus.
AB  - The role of Asp-328 and Ile-329 as a cofactor discrimination site of the NAD
      dependent isocitrate dehydrognase (NAD-IDH) from Pyrococcus furiosus has been
      verified by replacing these residues with Lys and Tyr, respectively, which are
      the corresponding residues in NADP-IDH from Escherichia coli. The Asp-328-Lys
      mutant showed dual coenzyme specificity, whereas introduction of the double
      mutation, Asp-328-Lys/Ile-329-Tyr shifted the cofactor preference from NAD to
      NADP. NADP-dependent P. furiosus IDH retained thermostability and thermoactivity
      compared with NAD-IDH.

PMID- 12209264
TI  - Mesorhizobium amorphae, a rhizobial species that nodulates Amorpha fruticosa, is
      native to American soils.
AB  - Amorpha fruticosa was inoculated with rhizosphere soil from Iowa, USA, and 140
      rhizobia isolated from root nodules were compared with Mesorhizobium amorphae
      originating from Chinese soils. PCR-RFLP patterns of the 16S rRNA gene from the
      isolates and from M. amorphaewere the same. All isolates had a symbiotic plasmid
      of the same size with a single nifHgene. DNA:DNA hybridization values, DNA G+C
      content, and induced Nod factor patterns also were similar. We concluded that the
      four genotypes distinguished among 53 representative American isolates were M.
      amorphae. Since A. fruticosa is native to the Americas and is highly specific in
      its nodulation requirement, M. amorphae probably was transmitted to China.

PMID- 12209265
TI  - Juxtaposition of signal-peptide charge and core region hydrophobicity is critical
      for functional signal peptides.
AB  - In Escherichia coli, exported proteins are synthesized as precursors containing
      an amino-terminal signal peptide which directs transport through the translocase
      to the proper destination. We have constructed a series of signal peptide
      mutants, incorporating linker sequences of varying lengths between the amino
      terminal charge and core region hydrophobicity, to examine the requirement for
      the juxtaposition of these two structural features in promoting protein
      transport. In vivo and in vitro analyses indicated that high transport efficiency
      via signal peptides with core regions of marginal hydrophobicity absolutely
      requires the proximity of sufficient charge.

PMID- 12209266
TI  - The relationship of temperature to desiccation and starvation tolerance of the
      Mycobacterium avium complex.
AB  - Mycobacterium avium grew in media at 14-37 degrees C, and persisted at 4 degrees
      C and 42 degrees C. The bacteria lost approximately 90% viability after 3 months
      in reverse-osmosis deionized water at 4-37 degrees C. Cooler temperatures lowered
      the death rate. Death rates also decreased after a 5- to 10-day starvation
      adaptation period. Alterations of the steady-state levels of different mycolic
      acid classes, presumably to facilitate thermoadaptation, were found. Following
      desiccation, M. avium lost viability at a constant rate (half-life of 2.3 days).
      This implies that bacilli contaminating dry medical surfaces would persist for
      short periods of time. The remarkable stress survival exhibited by M. avium
      further suggests persistence in a range of environmental and clinical settings.

PMID- 12209267
TI  - Opening the microcirculation: can vasodilators be useful in sepsis?
AB  - OBJECTIVE: A prominent feature of sepsis is dysfunction of the microcirculation,
      with impaired perfusion and regional tissue oxygenation causing a deficit in
      oxygen extraction. If shunting of oxygen transport past closed hypoxic
      microcirculatory beds is responsible for this, vasodilator therapy, which raises
      the driving pressure of the microcirculation and thereby promotes flow, could
      recruit such shunted microcirculatory units and improve tissue oxygenation.
      DESIGN: A literature search was conducted in Medline for evidence of this
      expected benefit of vasodilators in sepsis. METHODS: Studies were searched using
      the keyword for vasodilating drugs in combination with "sepsis," "septic,"
      "multiple organ failure," or "critically ill patients." The search included
      animal and clinical investigations but only where the effects of vasodilator
      therapy were demonstrated by regional measures of oxygen transport variables
      (e.g., oxygen extraction variables, regional ischemia, microcirculatory flow or
      tissue oxygenation measurements). The vasodilating drugs investigated included
      prostacyclin, pentoxifylline, N-acetyl-cysteine, and nitric oxide donors used in
      animal and human sepsis. RESULTS: Prostacyclin and nitric oxide donors are the
      best studied vasodilating agents in experimental sepsis and have shown improved
      tissue perfusion and oxygen extraction. In several clinical studies prostacyclin
      has also been shown to have such beneficial effects. Recent studies using
      orthogonal polarization spectral imaging have shown microcirculatory recruitment
      by nitric oxide donors in hemodynamically resuscitated septic patients. Whether
      such therapeutic modalities aimed at recruitment of the microcirculation improve
      outcome, however, still has to be determined.

PMID- 12209268
TI  - Predictive value of procalcitonin and interleukin 6 in critically ill patients
      with suspected sepsis.
AB  - OBJECTIVE: To evaluate the performance of procalcitonin (PCT), interleukin-6 (IL
      6), C-reactive protein, leukocyte count, D-dimer, and antithrombin III at onset
      of septic episode and 24 h later in prediction of hospital mortality in
      critically ill patients with suspected sepsis. DESIGN AND SETTING: Prospective,
      cohort study in two university hospital intensive care units. PATIENTS: 61
      critically ill patients with suspected sepsis. MEASUREMENTS AND RESULTS: The
      outcome measure was hospital mortality. Hospital survivors ( n=41) and
      nonsurvivors ( n=20) differed statistically significantly on day 1 (admission) in
      PCT, IL-6, SOFA score, and APACHE II score, and 24 h later in PCT, IL-6, and D
      dimer values. AT III, CRP, and leukocyte count did not differ. The areas under
      receiver operating curves showed reasonable discriminative power (>0.75) in
      predicting hospital mortality only for day 2 IL-6 (0.799) and day 2 PCT (0.777)
      values which were comparable to that of APACHE II (0.786), and which remained the
      only independent predictor of mortality. CONCLUSIONS: Admission and day 2 IL-6,
      and day 2 PCT, and day 2 D-dimer values differed significantly between hospital
      survivors and nonsurvivors among critically ill patients with suspected sepsis.
      However, in prediction of hospital mortality, only the discriminative power of
      day 2 PCT and IL-6 values, and APACHE II was reasonable as judged by AUC analysis
      (>0.75).

PMID- 12209269
TI  - Noninvasive pressure support ventilation in non-COPD patients with acute
      cardiogenic pulmonary edema and severe community-acquired pneumonia: acute
      effects and outcome.
AB  - OBJECTIVE: To compare the acute effects of noninvasive pressure support
      ventilation (NIPSV) in non-COPD patients with acute cardiogenic pulmonary edema
      (CPE) and severe community-acquired pneumonia (CAP) presenting with a similar
      hypoxemic respiratory failure and exploring the ensuing impact on outcome.
      DESIGN. Prospective, observational study. SETTING. Multidisciplinary ICU,
      regional teaching hospital. PATIENTS: Non-COPD patients with CPE or severe CAP.
      MEASUREMENTS AND RESULTS: Fifteen patients with CPE and eighteen with CAP were
      included. Both groups had similar low PaO2/FiO2 ratios at admission; SAPS II,
      baseline pH(a) were lower in the CPE group than in the CAP group. Within the
      first NIPSV observation period (60 min), the oxygenation improved significantly
      in both CPE and CAP-groups; respiratory rate (RR) significantly decreased in the
      CPE group ( P=0.005), but it remained unchanged in the whole CAP group; heart
      rate and mean arterial pressure significantly decreased in both groups. One
      patient (6.6%) in the CPE group and seven patients (38%) in the CAP group were
      intubated ( P=0.04). The mean total time spent on NIPSV was 9.6+/-6.3 h in the
      CPE and 37.2+/-36 h in the CAP group ( P=0.01). Unit mortality rate was 6.6% in
      the CPE and 28% in the CAP group ( P=0.2). Upon inclusion, all but one CAP
      patients who were subsequently intubated had a bacteremic pneumonia; unit
      mortality rate was 57% in intubated- and 9% in non-intubated CAP patients (
      P=0.05). CONCLUSIONS: NIPSV equally and rapidly improved oxygenation in non-COPD
      patients with CPE and severe CAP presenting with a similar hypoxemic respiratory
      failure, but the subsequent outcome was definitely different in the two groups,
      depending on the nature of the acute lung injury.

PMID- 12209270
TI  - Noninvasive ventilation for treating acute respiratory failure in AIDS patients
      with Pneumocystis carinii pneumonia.
AB  - OBJECTIVE: To compare noninvasive positive pressure ventilation (NPPV) vs.
      invasive mechanical ventilation in AIDS patients with Pneumocystis carinii
      pneumonia (PCP)-related acute respiratory failure (ARF). DESIGN: A single-center,
      prospective, case-control trial. SETTING: An ICU of a private tertiary hospital
      specialized in infectious disease. PATIENTS: Forty-eight AIDS patients with
      severe PCP-related ARF needing mechanical ventilation. INTERVENTIONS: Twenty-four
      patients treated with NPPV by a facial mask strictly matched with 24 patients
      treated with invasive ventilation by endotracheal intubation. RESULTS: Use of
      NPPV avoided intubation in 67% of patients, and avoidance of intubation was
      associated with improved survival (100% vs. 38%; P=0.003). NPPV-treated patients
      required fewer invasive devices ( P<0.001) and had a lower incidence of
      pneumothoraces (8.3% vs. 37.5%; P=0.039). The NPPV-treated group required a nurse
      workload similar to that of the conventional ventilation group, but this group
      had a shorter duration of stay in the ICU ( P=0.013). The NPPV-treated group had
      a lower mortality in the ICU, the hospital and within 2 months of study entry.
      Differences in mortality between the two groups disappeared after 6 months.
      CONCLUSIONS: The findings of this study seem to provide further support for
      applying NPPV in AIDS patients with severe PCP-related ARF as a first-line
      therapeutic choice, but randomized controlled trials are required to confirm our
      results.

PMID- 12209271
TI  - Effects of positive end-expiratory pressure on dead space and its partitions in
      acute lung injury.
AB  - OBJECTIVE: A large tidal volume (VT) and lung collapse and re-expansion may cause
      ventilator-induced lung injury (VILI) in acute lung injury (ALI). A low VT and a
      positive end-expiratory pressure (PEEP) can prevent VILI, but the more VT is
      reduced, the more dead space (VD) compromises gas exchange. We investigated how
      physiological, airway and alveolar VD varied with PEEP and analysed possible
      links to respiratory mechanics. SETTING: Medical and surgical intensive care unit
      (ICU) in a university hospital. DESIGN: Prospective, non-randomised comparative
      trial. PATIENTS. Ten consecutive ALI patients. INTERVENTION: Stepwise increases
      in PEEP from zero to 15 cm H2O. MEASUREMENTS AND RESULTS: Lung mechanics and VD
      were measured at each PEEP level. Physiological VD was 41-64% of VT at zero PEEP
      and increased slightly with PEEP due to a rise in airway VD. Alveolar VD was 11
      38% of VT and did not vary systematically with PEEP. However, in individual
      patients a decrease and increase of alveolar VD paralleled a positive or negative
      response to PEEP with respect to oxygenation (shunt), respectively. VD fractions
      were independent of respiratory resistance and compliance. CONCLUSIONS: Alveolar
      VD is large and does not vary systematically with PEEP in patients with various
      degrees of ALI. Individual measurements show a diverse response to PEEP.
      Respiratory mechanics were of no help in optimising PEEP with regard to gas
      exchange.

PMID- 12209272
TI  - Detecting lung injury in patients with pulmonary edema.
AB  - OBJECTIVE: Current entry rules for clinical trials of acute lung injury (ALI)
      depend on clinical criteria and arterial blood gas measurements. The objective of
      this study was to determine whether estimates of pulmonary vascular permeability
      could be used to more accurately identify patients with ALI for this purpose.
      DESIGN AND SETTING: Cross-sectional study in a university hosptial in a large
      metropolitan city. PATIENTS AND PARTICIPANTS: 21 patients with noncardiogenic
      pulmonary edema, 7 patients with hydrostatic forms of pulmonary edema, and 10
      healthy volunteers. INTERVENTIONS: Positron emission tomographic (PET) imaging
      with (68)Ga-labeled transferrin, or gamma-camera scintigraphy (gamma-S) with
      (99m)Tc-labeled albumin. All patients were studied within 24 h of onset, and all
      were selected exclusively on the basis of radiographic, not clinical, criteria.
      PET estimates of PTCER were used as a "gold standard." MEASUREMENTS AND RESULTS:
      Radioactivity data were analyzed to compute the pulmonary transcapillary escape
      rate (PTCER) and the normalized slope index. PTCER by gamma-S was more strongly
      correlated to PTCER(PET) than normalized slope index by gamma-S. Although
      PTCER(gamma) was significantly correlated with PaO2/FIO2, it did not distinguish
      patients with noncardiogenic pulmonary edema from those with hydrostatic
      pulmonary edema. CONCLUSIONS: These data cast doubt on whether the gamma-S method
      can be used as a screening tool in clinical trials of ALI.

PMID- 12209273
TI  - Comparative bench study of triggering, pressurization, and cycling between the
      home ventilator VPAP II and three ICU ventilators.
AB  - OBJECTIVE: To compare triggering, pressurization, and cycling of the home
      ventilator VPAP II with those of three ICU ventilators (Evita 4, Galileo, and
      Servo 300). DESIGN AND SETTING: Two-compartment lung model study in a research
      laboratory, university hospital. METHODS: One compartment was driven by an ICU
      ventilator to mimic "patient" inspiratory effort, while the other was connected
      to the tested ventilator. Pressure support of 10, 15, 20, and 25 cmH2O, and
      inspiratory efforts of 5, 10, 15, 20, and 25 cmH2O (inspiratory time 1 s) were
      used in normal, obstructive, and restrictive conditions. Triggering delay (Td),
      triggering workload, pressurization at 300 and 500 ms, and difference between the
      "patient's" inspiratory time and that of the ventilator were analyzed. RESULTS:
      No difference was noted in triggering workload between VPAP II, Evita 4, and
      Galileo while Servo 300 had a lower value. Pressurization at 300 ms on Evita 4
      and Servo 300 reached 75% of the ideal value, on Galileo 35%, and on VPAP II 45%.
      Pressurization at 500 ms on Evita 4 and Servo 300 reached 85% of the ideal value,
      on Galileo 50%, and on VPAP II 55%. Cycling was delayed in obstructive conditions
      and premature in restrictive conditions with each of the devices. CONCLUSIONS:
      The VPAP II performed as well as one ICU ventilator and less well than two. Home
      devices for noninvasive ventilation in acute respiratory failure outside the ICU
      could prove attractive as they are smaller, less costly, and easier to use than
      ICU machines.

PMID- 12209274
TI  - Single-dilator percutaneous tracheostomy: a comparison of PercuTwist and Ciaglia
      Blue Rhino techniques.
AB  - OBJECTIVE: To compare two single-dilator percutaneous tracheostomy techniques,
      Ciaglia Blue Rhino and the new PercuTwist technique. DESIGN AND SETTING:
      Randomized, observational clinical trial in patients undergoing elective
      percutaneous tracheostomy in the intensive care units of a university hospital.
      PATIENTS: Seventy consecutive, adult patients undergoing either Blue Rhino (
      n=35) or PercuTwist tracheostomy ( n=35). INTERVENTIONS: Performance of
      percutaneous tracheostomy with a novel screwlike dilating device (PercuTwist) or
      conically shaped, flexible rubber dilator (Blue Rhino). RESULTS: Stoma dilation
      was successful with the respective device in all patients. While subsequent
      tracheostomy cannula insertion was uneventful in all but one patients undergoing
      the Blue Rhino technique, it was difficult or even impossible in eight patients
      who underwent PercuTwist tracheostomy. Regarding serious and intermediate
      procedural-related complications, two cases of posterior tracheal wall injury
      occurred with the PercuTwist technique. No serious or intermediate complications
      were noted during Blue Rhino tracheostomy. There was no statistical significance
      between the two techniques in terms of minor and overall complications.
      CONCLUSIONS: So far the new PercuTwist technique represents an alternative to the
      established Blue Rhino technique. Nonetheless, the two cases of posterior
      tracheal wall injury should not be underestimated, on the one hand, but, on the
      other, may be attributed to a learning curve with a new technique. The new
      PercuTwist technique should be performed by various teams and in a considerably
      larger numbers of patients before an ultimate rating can be made.

PMID- 12209275
TI  - The cuff leak test to predict failure of tracheal extubation for laryngeal edema.
AB  - OBJECTIVE: Laryngeal edema secondary to endotracheal intubation may require early
      re-intubation. Prior to extubation the absence of leak around an endotracheal
      tube may predict laryngeal edema after extubation. We evaluated the usefulness of
      a quantitative assessment of such a leak to identify the patients who will
      require early re-intubation for laryngeal edema. METHODS: This prospective study
      included 76 patients with endotracheal intubation for more than 12 h. The leak,
      in percent, was defined as the difference between expired tidal volume measured
      just before extubation, in volume-controlled mode, with the cuff inflated and
      then deflated. The best cut-off value to predict the need for re-intubation for
      significant laryngeal edema was determined and the patients were divided into two
      groups, according to this cut-off value. RESULTS: Eight of the 76 patients (11%)
      needed re-intubation for laryngeal edema. Patients requiring re-intubation had a
      smaller leak than the other patients [9 (3-18) vs 35 (13-53)%, p<0.01]. The best
      cut-off value for gas leak was 15.5%. The high leak group included 51 patients,
      of whom only two patients (3%) required re-intubation. The low leak group
      included 25 patients, among whom six patients (24%) required re-intubation (
      p<0.01). The sensitivity of this test was 75%, the specificity 72.1%, the
      positive predictive value 25%, the negative predictive value 96.1% and the
      percent of correct classification 72.4%. CONCLUSIONS: A gas leak around the
      endotracheal tube greater than 15.5% can be used as a screening test to limit the
      risk of re-intubation for laryngeal edema.

PMID- 12209276
TI  - Conventional monitoring and intravascular volume measurement can lead to
      different therapy after upper gastrointestinal tract surgery.
AB  - OBJECTIVE: The purpose of this study was to compare the judgment of intravascular
      volume based either on conventional monitoring or on the data of COLD
      measurement. DESIGN: Single-blinded, observational study. SETTING: Intensive care
      unit (ICU). PATIENTS: Ten consecutive patients after upper gastrointestinal tract
      surgery for carcinoma. MEASUREMENTS AND RESULTS: Judgments ( n=59) about
      intravascular volume (hypo-, iso- or hypervolemic) were given twice a day until
      the 2nd postoperative day by two physicians. Physician A's judgment was based on
      conventional monitoring and physician B's judgment on COLD monitoring. Both were
      blinded for each other's judgment. The inter-rater agreement between A and B was
      analyzed using the weighted kappa statistic. Both physicians gave a
      recommendation about the volume therapy during the following 12 h. The
      therapeutic regimen, including volume therapy, was defined by physician A. The
      inter-rater-agreement regarding intravascular volume was poor (overall weighted
      kappa =0.095). The sum of absolute differences between A and B in their
      recommendation about infusion administration reached a median of 4,875 ml per
      patient. CONCLUSIONS: The poor inter-rater agreement between the two physicians
      and the consecutive difference in the infusion therapy may have clinical
      consequences and should be evaluated in further studies. These data cannot
      confirm which decision strategy should be preferred.

PMID- 12209277
TI  - Comparison of continuous thermodilution and bolus cardiac output measurements in
      septic shock.
AB  - OBJECTIVE: To compare continuous (CCO) and bolus (BCO) thermodilution cardiac
      output measurement techniques over a wide range of cardiac outputs and blood
      temperatures in a septic sheep model. DESIGN AND SETTING: Prospective
      experimental study in a university intensive care laboratory. SUBJECTS: Thirty
      five anesthetized sheep. INTERVENTIONS: Pulmonary artery catheters allowing
      measurement of CCO and BCO were placed through the external jugular vein. Cecal
      ligation and perforation was performed to induce septic shock. In 14 sheep two
      femoral venous catheters were placed and connected to a hemofiltration system to
      alter blood temperature. MEASUREMENTS: CCO and BCO were measured every hour
      during the experiment. Three 10-ml bolus injections of iced normal saline were
      given through a closed injectate system and then averaged. The CCO readings were
      collected just before the BCO measurements. The relationship between CCO and BCO
      was assessed using Bland and Altman's method. RESULTS: In 465 paired data the
      temperature ranged between 34.0 degrees and 40.9 degrees C, CCO between 1.4 and
      17.0 l/min, and BCO between 1.1 and 17.4 l/min. There was a highly significant
      correlation between CCO and BCO ( r=0.97). The bias (difference between CCO and
      BCO) was -0.19 l/min, the SD of the difference 0.45 l/min, and the limits of
      agreement -1.08/0.71 l/min. There were also highly significant correlations
      between CCO and BCO at the different temperatures (extreme values: 34.0-34.9
      degrees C, r=0.90; 40.0-40.9 degrees C, r=0.98). CONCLUSIONS: Thermodilution
      measurements of CCO are reliable, when compared to BCO measurements, over a large
      range of cardiac outputs and blood temperatures.

PMID- 12209278
TI  - Short-term treatment of severe hypertension of pregnancy: prospective comparison
      of nicardipine and labetalol.
AB  - OBJECTIVES: To assess the efficacy and safety of nicardipine in comparison to
      labetalol in the initial management of severe hypertension in pregnancy. DESIGN.
      Randomized prospective study. SETTING: The obstetric ward of the teaching
      hospital of Monastir Tunisia. PATIENTS: Sixty consecutive pregnant women admitted
      beyond the 24th week of pregnancy with severe hypertension. INTERVENTION:
      Patients were randomly assigned to receive intravenously for 1 h either labetalol
      ( n=30) or nicardipine ( n=30). Treatment was titrated to achieve a 20% lowering
      of blood pressure (BP). MEASUREMENTS: Maternal BP and heart rate were measured at
      inclusion and repeatedly during the first hour following the drugs
      administration. Fetal heart rate was recorded throughout the study period. The
      main outcome endpoints were the success rate and the length of time needed to
      achieve the therapeutic goal. The rate of maternal and fetal adverse events and
      dose adjustments were also analyzed. RESULTS: Labetalol and nicardipine achieved
      the 20% lowering in BP in the same proportion (63% and 70% success rates,
      respectively). Overall nicardipine caused a significantly greater decrease in
      systolic and diastolic BP. No patient had any episode of hypotension. The length
      of time to achieve the BP goal was also similar (12 vs. 11 min, respectively).
      Both drugs were well tolerated except for a moderate tachycardia observed with
      the use of nicardipine. CONCLUSION: Nicardipine and labetalol are effective and
      safe in the initial treatment of severe hypertension of pregnancy.

PMID- 12209279
TI  - Waiting for the break of dawn? The effects of discharge time, discharge TISS
      scores and discharge facility on hospital mortality after intensive care.
AB  - OBJECTIVE: To assess the effects of discharge Therapeutic Intervention Scoring
      System (TISS) scores, discharge time and type of discharge facility on ultimate
      hospital mortality after intensive care. DESIGN: Retrospective cohort study.
      SETTING: General intensive care unit (ICU) in a district general hospital.
      PATIENTS AND PARTICIPANTS: One thousand six hundred fifty-four ICU patients
      discharged to hospital wards or high dependency units (HDUs). MAIN MEASUREMENTS
      AND RESULTS: Vital status at ultimate hospital discharge was the main outcome
      measurement. The crude hospital mortality after ICU discharge (12.6%) was
      significantly associated with increasing discharge TISS scores (chi(2) for trend
      =9.0, p=0.028). This trend was similarly observed after adjusting for severity of
      disease. Patients with high TISS scores (>30) who were discharged to hospital
      wards had a higher risk (1.31; CI: 1.02-1.83) of in-hospital death compared with
      patients discharged to HDUs. Crude mortality was significantly higher for late
      20.00 h to 7.59 h) than for early (8.00 h to 19.59 h) discharges (18.8% versus
      11.2%, chi(2) =12.1, p=0.0004). Adjusted for disease severity, the mortality risk
      was 1.70-fold (CI: 1.28-2.25) increased for late ICU discharges. Patients
      discharged late to hospital wards had significantly higher severity-adjusted
      risks (1.87; CI:1.36-2.56) than had patients discharged to HDUs (1.35; CI: 0.77
      2.36). CONCLUSIONS: Both late discharge and high discharge TISS scores are
      indicators of "premature" ICU discharge and were associated with increased
      mortality. Intermediate care reduced the mortality of patients discharged
      "prematurely" from ICU. This adds to the growing evidence of the benefits of
      intermediate care after ICU discharge.

PMID- 12209280
TI  - Outcome and prognostic features of intensive care unit treatment in patients with
      hematological malignancies.
AB  - OBJECTIVE: To assess the outcome of intensive care unit (ICU) treatment in
      patients with hematological malignancies. DESIGN AND SETTING: Retrospective
      cohort study in the medical ICU of a university hospital. PATIENTS: 104
      critically ill patients after receiving conventional chemotherapy or autologous
      hematopoietic stem cell transplantation. INTERVENTIONS: We analyzed demographic
      data, underlying disease, intensity of antineoplastic regimen, cause of
      admission, need for mechanical ventilation, and hemofiltration, ICU survival, and
      survival after discharge, furthermore neutrophil count, C-reactive protein
      (<or=150 vs. >150 mg/l), antithrombin III, prothrombin time, and SAPS II (<or=50
      vs. >50) at ICU admission. All recorded variables were evaluated for prognostic
      relevance by univariate and multivariate analyses. MEASUREMENTS AND RESULTS:
      Overall ICU mortality was 44%, with significantly higher mortality in ventilated
      patients (74% vs. 12% in nonventilated patients, p<0.001). Overall survival for
      the entire group 6 months and 1 year after ICU admission was 33% and 29%,
      respectively. Multivariate analysis revealed mechanical ventilation and SAPS II
      as independent prognostic factors of both ICU mortality and long-term survival,
      while C-reactive protein predicted only ICU mortality. CONCLUSIONS: The outcome
      of patients not requiring ventilatory support in this study was encouraging,
      while invasive ventilation was again confirmed as predicting a dismal prognosis
      in this population. Efforts should be directed to avoiding this procedure by
      reducing the pulmonary toxicity of antineoplastic treatment and to making
      ventilatory support more tolerable.

PMID- 12209281
TI  - Endocrine measurements in survivors and non-survivors from critical illness.
AB  - OBJECTIVE: To compare measurements of thyroid and adrenal function between
      survivors and non-survivors in critical illness. DESIGN AND SETTING: Prospective,
      observational study at the medical/surgical intensive care unit (ICU) at Royal
      Infirmary of Edinburgh, Scotland. PATIENTS: 163 patients admitted to the
      intensive care unit over a 4-month period. INTERVENTIONS: We took blood samples
      within 1 h of ICU admission, and at 08:00 hours on the subsequent 2 days of ICU
      admission. We measured serum total (TT(4)) and free (fT(4)) thyroxine, total
      (TT(3)) and free (fT(3)) tri-iodothyronine, thyrotropin (TSH) and plasma cortisol
      concentrations. MEASUREMENTS AND RESULTS: TT(3) and TT(4) concentrations were
      significantly less in non-survivors than in survivors on admission and on day 1
      but not on day 2. Cortisol concentrations were higher in non-survivors on
      admission and on day 1 but not on day 2. TSH, fT(3) and fT(4) concentrations did
      not differ significantly between survivors and non-survivors at any time. Only
      TT(4) and cortisol were independent predictors of outcome. Prediction of outcome
      from the admission sample values was not better than using APACHE II scoring.
      CONCLUSIONS: Thyroid hormone and cortisol concentrations differ between survivors
      and non-survivors on admission to intensive care, but the values overlap. These
      differences do not allow accurate prediction of outcome from critical illness.

PMID- 12209282
TI  - A four-step protocol for limitation of treatment in terminal care. An
      observational study in 475 intensive care unit patients.
AB  - OBJECTIVE: To describe a four-step protocol for withholding and withdrawal of
      life support (WH/WDLS) in intensive care unit (ICU) terminal patients. DESIGN:
      Observational study. SETTING: A 10-bed ICU of a general hospital. PATIENTS:
      Eighty-three patients out of 475 consecutive patients admitted over a 1 year
      period had WH/WDLS. INTERVENTIONS: The healthcare team chose a pattern of
      treatment limitation on a four-step protocol for every patient every day. There
      were four alternatives: group 1: no limitation of care; group 2: patient
      designated do not resuscitate (DNR) and pressors limited to dopamine at a maximum
      dose of 20 microg/kg per min; others therapies were continued; group 3: active
      withdrawal of all therapy except comfort care, i.e., the patient continued to
      receive nursing, sedation/analgesia, hydration and mechanical ventilation with
      FIO2=0.21 and no positive end-expiratory pressure (PEEP). Sedation was adjusted
      to Ramsay 3-4. The group 4 was treated the same as group 3 except that minute
      ventilation was 5 l/min and sedation/analgesia adjusted to Ramsay 6. WH/WDLS was
      performed only if the full ICU staff and all family members agreed with the
      procedure. WH/WDLS was documented in the patient's chart. RESULTS: Withholding
      and withdrawal of life support was performed in 83 patients (17%): 25 patients in
      group 2 (15 deaths), 36 patients in group 3 (36 deaths) and 22 patients in group
      4 (22 deaths). Finally, 73 patients died after WH/WDLS. ICU stay was 10+/-17
      days, time from admission to WH/WDLS was 184+407 h and time from WH/WDLS to death
      was 64+/-84 h. CONCLUSION: This four-step protocol may promote medical decision
      making on end-of-life care.

PMID- 12209283
TI  - Quality of reporting of randomised controlled trials in the intensive care
      literature. A systematic analysis of papers published in Intensive Care Medicine
      over 26 years.
AB  - OBJECTIVE: To assess the number and quality of the reporting of randomised
      controlled trials (RCTs) published in Intensive Care Medicine. DESIGN: Systematic
      revision. SETTING: Randomised controlled trials published in Intensive Care
      Medicine. STUDY SELECTION: All RCTs published in this journal from its birth to
      December 2000 identified by MEDLINE and our own research. MEASUREMENTS AND
      RESULTS: The Jadad scale and the individual assessment of key methodological
      components, namely the randomisation process, blinding and reporting and handling
      of loss to follow-up, were used to evaluate the quality of reporting. Other
      information was extracted regarding the design characteristics and the analytical
      approach. 173 RCTs, 63% of which were from European countries, were analysed.
      Adequately reported RCTs according to a Jadad scale score of more than 2 were 44
      (25.4%). Analysis of individual methodological components revealed a variable
      percentage of adequate reporting ranging from 3.5% for randomisation to 10.4% for
      blinding and to 49.1% for loss to follow-up. Sample sizes were small with a
      median of 30 patients and rationale for its estimation was reported in 7.5%.
      Despite this, 81.5% of RCTs reported statistically significant results,
      suggesting that the treatment effects were strong or that a publication bias
      existed or that the uncertainty principle was not fulfilled. CONCLUSIONS:
      Randomised controlled trials offer the best evidence of the efficacy of medical
      interventions, provided that high standards of transparent reporting are used.
      More resolute attention to the methodological quality of reporting and adherence
      to recently published guidelines (CONSORT II) may help to achieve this result.

PMID- 12209284
TI  - Diagnostic accuracy of G-CSF, IL-8, and IL-1ra in critically ill children with
      suspected infection.
AB  - OBJECTIVE: To elucidate the diagnostic accuracy of granulocyte colony-stimulating
      factor (G-CSF), interleukin-8 (IL-8), and interleukin-1 receptor antagonist (IL
      1ra) in identifying patients with sepsis among critically ill pediatric patients
      with suspected infection. DESIGN AND SETTING: Nested case-control study in a
      multidisciplinary neonatal and pediatric intensive care unit (PICU) PATIENTS:
      PICU patients during a 12-month period with suspected infection, and plasma
      available from the time of clinical suspicion (254 episodes, 190 patients).
      MEASUREMENTS AND RESULTS: Plasma levels of G-CSF, IL-8, and IL-1ra. Episodes
      classified on the basis of clinical and bacteriological findings into: culture
      confirmed sepsis, probable sepsis, localized infection, viral infection, and no
      infection. Plasma levels were significantly higher in episodes of culture
      confirmed sepsis than in episodes with ruled-out infection. The area under the
      receiver operating characteristic curve was higher for IL-8 and G-CSF than for IL
      1ra. Combining IL-8 and G-CSF improved the diagnostic performance, particularly
      as to the detection of Gram-negative sepsis. Sensitivity was low (<50%) in
      detecting Staphylococcus epidermidis bacteremia or localized infections.
      CONCLUSIONS: In this heterogeneous population of critically ill children with
      suspected infection, a model combining plasma levels of IL-8 and G-CSF identified
      patients with sepsis. Negative results do not rule out S. epidermidis bacteremia
      or locally confined infectious processes. The model requires validation in an
      independent data-set.

PMID- 12209285
TI  - A comparison of two mortality risk scores for very low birthweight infants:
      clinical risk index for babies and Berlin score.
AB  - OBJECTIVE: To compare the performance of two mortality risk scores for very low
      birthweight (VLBW) infants. DESIGN AND SETTING: Cohort study in two university
      associated neonatal tertiary care units. PATIENTS: . The clinical risk index for
      babies and the Berlin score were assessed in 343 VLBW infants (below 1500 g)
      admitted to one center and 257 infants admitted to a second center between 1992
      and 1996. An additional 572 VLBW infants admitted at the former center during
      1978-1987 and 294 during 1988-1991 were studied for changes in risk-adjusted
      mortality over time. MEASUREMENTS AND RESULTS: Goodness of fit was excellent for
      both scores in both centers. Ability of discrimination was similarly high for
      both scores. The area under the receiver operating characteristic curves for all
      600 infants was 0.84 for the clinical risk index for babies, 0.82 for the Berlin
      score, and 0.77 for birthweight alone. Both scores discriminated less well in the
      present samples than they did in the populations in which they were developed.
      Applying the Berlin score in three periods revealed a continuous decrease in risk
      adjusted mortality from 1978 to 1996, indicating improvement in neonatal care.
      CONCLUSIONS: Both scores predicted death in hospital with high accuracy and
      interhospital reliability. Decreasing mortality in VLBW infants during the past
      20 years requires regular reevaluation of existing scoring systems to avoid
      overestimation of mortality risk.

PMID- 12209286
TI  - Pulse oximeter-enhanced accuracy of capnometry in children with cyanotic heart
      disease.
AB  - OBJECTIVES: To evaluate the relationship between the arterial end-tidal partial
      pressure of carbon dioxide (PCO2) difference (deltapCO2) and the degree of
      desaturation in children with cyanotic heart disease (CHD) and to come to a more
      reliable estimation of the arterial carbon dioxide partial pressure (PaCO2) from
      the end-tidal carbon dioxide partial pressure (PET-CO2). DESIGN AND SETTING: In
      part retrospective, in part prospective observational study at a university
      children's hospital. SUBJECTS AND INTERVENTIONS: We retrospectively assessed the
      relationship between the arterial oxygen saturation as measured by means of pulse
      oximetry (SpO2) and the arterial to end-tidal PCO2 differences (deltaPCO2) from
      the records of medical or surgical interventions in 43 patients with CHD. We
      derived a PaCO2-PET-CO2 correction formula that was prospectively validated in 34
      patients with CHD. MEASUREMENTS AND RESULTS: In the retrospective part we found a
      significant correlation between SpO2 and deltaPCO2 ( r (2)=0.84, p<0.001). The
      regression equation (corrected PET-CO2=raw PET-CO2-0.36xSpO2+39) was used in the
      prospective part to calculate the corrected PET-CO2. The r (2)s for the
      correlations between PaCO(2) and uncorrected and corrected PET-CO2 were 0.17 (
      p<0.05) and 0.94 ( p<0.001), respectively. The uncorrected PET-CO2 bias was 13.0
      mmHg, the bias +/- 2SDs was -0.1 and 26.2 mmHg. The corrected PET-CO2 bias was 
      0.6 mmHg, the bias +/- 2SD's was -4.0 and 2.9 mmHg. CONCLUSIONS: Correcting the
      PET-CO2 for the degree of hypoxia using the SpO2 in artificially ventilated
      infants and children with CHD results in a clinically applicable estimation of
      the PaCO2. As both SpO2 and PET-CO2 can be monitored continuously and non
      invasively, this could facilitate artificial ventilation management in children
      with CHD.

PMID- 12209287
TI  - Cytosine-phosphate-guanine (CpG) motifs are sensitizing agents for
      lipopolysaccharide in toxic shock model.
AB  - OBJECTIVE: Unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides
      are highly frequent motifs in bacterial DNA and rare in the mammalian genome.
      They are potent inducers of inflammatory cytokines and act synergistically with
      lipopolysaccharide (LPS) for the induction of tumor necrosis factor alpha (TNF
      alpha) production in vivo. It has therefore been suggested that innate immune
      reaction to bacterial unmethylated CpG motifs might contribute to the development
      of septic shock. We designed this study to assess the sensitization role of CpG
      motifs in LPS-induced shock using the D-galactosamine (D-GalN)-sensitized mouse
      model. DESIGN: A prospective, randomized in vivo animal laboratory study.
      SETTING: Experimental research laboratory. INTERVENTION: We performed experiments
      in which CpG, LPS and D-GalN were administrated sequentially in various orders or
      simultaneously in 8 week-old BALB/c mice. MEASUREMENTS AND RESULTS: Cytosine
      phosphate-guanine treatment potentiated LPS action only if injected prior to LPS.
      A combination of predefined sublethal doses of CpG (1 nmol/mouse) and LPS (1
      ng/mouse) not only had a synergetic effect on TNF-alpha production (20.3+/-9.2
      IU/ml versus 2.5+/-1.4 IU/ml and 5.6+/-3.4 IU/ml for CpG and LPS groups,
      respectively, p<0.05), but also led to animal death (5/5). An CpG effect requires
      de novo mRNA synthesis, since the sensitizing effect was inhibited by co
      administration of mRNA transcription inhibitors such as D-GalN and
      pentoxifylline, which is a specific TNF-alpha transcription inhibitor.
      Furthermore, CpG treatment provoked a strong TNF-alpha mRNA production in the
      liver that was dramatically reduced by pre-treatment with D-GalN. CONCLUSION: Our
      findings indicate that CpG motifs act synergistically with LPS by initializing
      the synthesis of TNF-alpha and/or TNF-alpha regulating factors, thereby acting as
      a sensitizing agent.

PMID- 12209288
TI  - Acute effects of non-invasive ventilatory support on functional mitral
      regurgitation in patients with exacerbation of congestive heart failure.
AB  - OBJECTIVE: The purpose of this study was to evaluate the acute effects of
      continuous positive airway pressure (CPAP) and bi-level airway pressure (BiPAP)
      on functional mitral regurgitation (MR) in patients with acute exacerbation of
      severe chronic congestive heart failure (CHF). DESIGN: A cross-over study.
      SETTING: A cardiopulmonary intensive care unit. PATIENTS AND INTERVENTIONS: Ten
      male patients affected by an acute exacerbation of congestive heart failure and
      hemodynamically significant MR were submitted to an echocardiograph color Doppler
      ultrasound evaluation during CPAP and BiPAP non-invasive ventilation. We analyzed
      left ventricle ejection fraction, area of MR and deceleration time (Dec-t).
      OUTCOME MEASURES: The primary end point was to evaluate whether CPAP and BiPAP
      were effective in reducing functional MR. RESULTS: After 30 min, the area of MR
      decreased from 10.0+/-2.7 to 8.0+/-2.9 cm(2) with CPAP and from 9.9+/-2.6 to
      8.6+/-2.6 cm(2) with BiPAP ( p<0.01); Dec-t increased from 120.9+/-12.7 to
      136.0+/-8.7 ms after CPAP and from 120.5+/-11.4 to 134.2+/-13.6 ms after BiPAP (
      p<0.01). CONCLUSION: In patients with exacerbation of severe CHF and functional
      MR, both modalities of non-invasive ventilation (CPAP and BiPAP) significantly
      improved ejection fraction and were equally effective in reducing MR.

PMID- 12209289
TI  - Procalcitonin: a marker to clearly differentiate systemic inflammatory response
      syndrome and sepsis in the critically ill patient?
AB  - OBJECTIVES: To define the role of procalcitonin in the differential diagnosis,
      prognosis and follow-up of critically ill patients. DESIGN: Prospective study
      during the 2-year period from January 1998-2000. PATIENTS: One hundred nineteen
      critically ill patients: 29 with systemic inflammatory response syndrome (SIRS)
      without any signs of infection, 11 with sepsis, 17 with severe sepsis, 10 with
      septic shock and 52 controls. Daily measurements of procalcitonin were performed
      by an immunocheminoluminometric assay, and values were correlated to the clinical
      characteristics of the patients. RESULTS: Mean concentrations of procalcitonin
      were 5.45 (95% CI: 2.11, 8.81), 7.29 (95% CI: -1.92,14.59), 6.26 (95% CI: -1.32,
      13.85) and 38.76 ng/ml (95% CI: 0.15, 77.38) on the 1st day in patients with
      SIRS, sepsis, severe sepsis and septic shock, respectively, and were
      statistically superior to those of control patients. Procalcitonin was gradually
      diminished over time with the resolution of the syndrome, while it was sustained
      in the same or more augmented levels upon worsening. Mean concentrations of
      procalcitonin on the 1st day for patients finally progressing to ARDS, to ARDS
      and acute renal failure, to ARDS, acute renal failure and DIC and to ARDS, acute
      renal failure, DIC and hepatic failure were 10.48, 8.08, 32.72 and 43.35 ng/ml,
      respectively. ROC curves of the sensitivity and specificity of procalcitonin for
      the evaluation of SIRS and sepsis were similar. CONCLUSIONS: The definite
      differential diagnosis between SIRS and sepsis may not rely on a single
      application of procalcitonin but on the complete clinical and laboratory
      evaluation of the patient with procalcitonin playing a considerable role.
      Procalcitonin is an early prognostic marker of the advent of MODS; therefore,
      daily determinations might help in the follow-up of the critically ill patient.

PMID- 12209290
TI  - Life-threatening hyperkalaemia following therapeutic barbiturate coma.
AB  - OBJECTIVE: To report the occurrence of life-threatening hyperkalaemia following
      treatment with therapeutic thiopentone coma. SETTING: The neurosurgical intensive
      care units of Royal North Shore Hospital and Liverpool Hospital, Sydney,
      Australia. PATIENTS: Three patients treated with theraputic thiopentone coma. One
      patient with raised intracranial pressure secondary to a severe traumatic brain
      injury and two patients with refractory vasospasm secondary to subarachnoid
      haemorrhage. Two of the three patients developed hypokalaemia on starting
      thiopentone, which was resistant to potassium supplementation. All three patients
      developed severe hyperkalaemia during the recovery phase of coma. This was life
      threatening in all three patients and fatal in one. CONCLUSIONS: Severe
      hypokalaemia refractory to potassium therapy may occur during therapeutic
      thiopentone coma. Severe rebound hyperkalaemia may occur after cessation of
      thiopentone infusion. Protocols for the management of patients with therapeutic
      barbiturate coma should recognise this potentially serious complication.

PMID- 12209291
TI  - A technique for the monitoring of blood flow during continuous haemofiltration.
AB  - OBJECTIVE: To establish a technique for the monitoring and graphic display of
      blood flow during continuous renal replacement therapy (CRRT). DESIGN AND
      SETTING: Technique assessment study in a tertiary intensive care unit. PATIENTS:
      Six ICU patients receiving CRRT. INTERVENTIONS: A technique was devised to
      monitor and graphically display blood flow during CRRT. This technique used a
      mini-ultrasound Doppler probe attached to the blood tubing with link to a lap top
      computer for quantitative graphic display. Blood flow was measured and displayed
      during routine treatment using this method in six patients. MEASUREMENTS AND
      RESULTS: Blood flow wave data were monitored and successfully displayed as a real
      time wave form and analysed using Windaq data analysis software. This initial
      analysis over a 6-h period revealed the following facts: (a) blood flow was not
      the same as set by the machine roller pump on nine occasions, (b) blood flow
      reductions defined as a drop in the 'diastolic' were 20% (seven) and 30% (two)
      less than set flow, (c) flow reductions frequently failed to trigger machine
      alarms, and (d) the blood flow wave displayed had unique characteristics.
      Complete flow monitoring was then undertaken for the functional life of one
      haemofilter over 24.5 h. There were 27 blood flow reductions, and blood flow was
      less than set for a total of 463.9 min or 31.5% of operating time. CONCLUSIONS:
      Blood flow during CRRT can be monitored by an ultrasound Doppler probe and
      displayed graphically. Preliminary data using this technique suggest potentially
      serious and undetected problems with blood flow during routine CRRT.

PMID- 12209292
TI  - Genetic analyses of the mouse deafness mutations varitint-waddler (Va) and jerker
      (Espnje).
AB  - Genetic studies on spontaneous mouse mutants with hearing defects have provided
      important insights into the function of genes expressed in inner ear hair cells.
      Here we report on our genetic analyses of the deaf mutants varitint-waddler (Va)
      and jerker (Espnje). A high-resolution genetic map localizes VaJ to a 0.14 +/-
      0.08 cM region between D3Mit85 and D3Mit259 on distal chromosome 3. By
      comparative mapping, the human ortholog resides at 1p22.3 between markers D1S3449
      and D1S2252. To study the effect of different genetic backgrounds on the hearing
      phenotype, Espnje and VaJ were crossed to various inbred strains. Auditory-evoked
      brainstem response tests on F2 progeny demonstrate that expression, inheritance,
      and penetrance of the hearing phenotype are solely controlled by the mutant
      allele. To test for a genetic interaction between Espnje and Cdh23v, auditory
      function was analyzed in double heterozygotes; no significant increases of
      thresholds of sound pressure levels were observed. The results establish the
      framework for cloning the Va gene and provide valuable insights into the genetics
      of deafness mutations in the mouse.

PMID- 12209293
TI  - Distribution and kinetic properties of GABAergic inputs to layer V pyramidal
      cells in rat auditory cortex.
AB  - Neocortical layer V is distinguished by both its pyramidal cells and its varied
      cortical and extracortical projections. Several studies suggest that the layer V
      pyramidal cell types, intrinsically bursting (IB) and regular spiking (RS) cells,
      differ both in the circuits in which they participate and in their inhibitory
      inputs. We quantified differences in inhibitory inputs to RS and IB cells using
      whole-cell voltage clamp techniques in the auditory cortex. We recorded miniature
      inhibitory postsynaptic currents (mIPSCs) and spontaneous IPSCs to gain kinetic,
      amplitude, and frequency information about GABAergic synapses. We then used focal
      sucrose applications to elicit mIPSC rate increases at the soma or dendrites of
      both cell types. We also electrically stimulated the axons giving rise to
      inhibitory synaptic inputs to measure minimally evoked IPSCs occurring at the
      soma or apical dendrites. We found that spontaneous and evoked IPSCs recorded
      from the auditory cortex have faster rise and decay kinetics when directly
      compared with those of the same layer V cells in other sensory cortical areas. We
      also found that mIPSCs observed in auditory IB and RS cells are different from
      one another. RS cell mIPSCs are larger and have faster rises and decays than IB
      cell mIPSCs, but IB cell mIPSCs occur more frequently. Focal sucrose application
      showed that most IB cell mIPSCs originate in the dendrites and are subject to
      dendritic filtering while most RS cell mIPSCs originate at the soma and are not
      filtered. These findings suggest that, first, IB and RS cells process their
      inputs in fundamentally different ways and, second, auditory cortical RS and IB
      cells may have specializations that allow them to process inhibitory inputs
      faster.

PMID- 12209294
TI  - 2002 - AHS meeting minutes at Tucson.
AB  - At the American Hernia Society meeting held in May 2002, researchers presented
      their experiences, techniques, and studies.

PMID- 12209295
TI  - Influence of laparotomy closure technique on collagen synthesis in the incisional
      region.
AB  - BACKGROUND: Variations of suture technique have an influence on the mechanical
      strength of laparotomy wounds. To investigate whether these differences in
      biomechanical properties influence collagen synthesis in the incisional region,
      an animal experiment on laparotomy closure was performed. MATERIAL: In 100 rats
      median laparotomies were closed with polypropylene. Continuous and single sutures
      were applied with variations of suture length to wound length (SLWL) ratio and
      suture tension. METHODS: Tissue samples from the incisional region after 2 and 4
      weeks were analysed spectro-photometrically for the concentration of collagen
      protein and by digital image analysis for the percentage of collagen type III.
      RESULTS: Running closure with an SLWL ratio >or=4:1 resulted in a significantly
      higher concentration of collagen protein than single sutures with the same SLWL
      ratio. In contrast, single closure with an SLWL ratio <4:1 led to in a higher
      collagen protein concentration than running closure with the same SLWL ratio.
      With an SLWL ratio >or=4:1 running sutures resulted in a significant reduction of
      the percentage of collagen type III after 4 weeks compared to single sutures.
      Closure with high suture tension led to a significant reduction of collagen
      protein between the 2nd and 4th week but left the percentage of collagen type III
      mostly unaffected. CONCLUSION: Suture technique, SLWL ratio, and suture tension
      have an effect on the ultrastructural composition of the regenerating tissue.
      This influence outlasts the period of tissue restructuring during which the
      presence of sutures in the incisional edges is absolutely required. Running
      sutures with an SLWL ratio >or=4:1 and low suture tension promote a favourable
      collagen composition of the incisional region.

PMID- 12209296
TI  - Lichtenstein inguinal herniorrhaphy using sutures versus tacks.
AB  - The Lichtenstein hernia repair has become a popular technique for most inguinal
      hernias performed in the United States. One attempt to improve on this technique
      includes the use of a tacker instead of suturing the mesh. This study compared
      the feasibility and time saving for placement of mesh for open inguinal hernias
      with a tacker versus polypropylene suture.Thirty-four patients were prospectively
      randomized to undergo open hernia repair using either running 2-0 polypropylene
      suture or a tacker device that contained spiral titanium tacks. Patients were
      examined after 1 week and followed for a mean of 8 months (range 1-26 months) to
      record postoperative complications and technical failure rate. Mesh placement
      times were significantly shorter in the tacker group (9.0+/-3.5 min) than the
      suture group (30.9+/-9.9 min). No technical complications or recurrences were
      found in the follow-up period in either group.Securing mesh with the tacker is
      safe, and repair appears durable at short-term follow-up. Using the tacker on
      open inguinal hernia repairs shortens the time for mesh placement compared to
      suture fixation. Decreased operative time may reduce overall cost.

PMID- 12209297
TI  - Intra-abdominal pressure: a reliable criterion for laparostomy closure?
AB  - BACKGROUND: Laparostomy is frequently performed in the surgical therapy of
      mechanical obstruction, peritonitis, or trauma to prevent abdominal compartment
      syndrome (ACS). Extended incisional hernia is inevitable when fascial closure is
      missed (up to 90% of cases). Intra-abdominal pressure (IAP) has not yet been
      evaluated as a criterion for the feasibility of fascial closure. PATIENTS AND
      METHODS: Over 12 months laparostomy was carried out in 40 patients. Definitive
      closure of the abdomen was performed after 4.4+/-3.7 days in 23 of these.
      Intravesical pressure was used to assess IAP before and after fascial closure.
      The resulting IAP was compared to the values of 90 patients undergoing elective
      abdominal surgery. Parameters of cardiocirculatory, renal, pulmonary, and liver
      function were also recorded. RESULTS: After closure of the laparostomy IAP
      increased significantly from 6.5+/-3.3 to 12.0+/-4.1 mmHg. Urine output decreased
      by 27% on the first postoperative day but regained normal levels thereafter. The
      central venous pressure increased by 31%. Other parameters of cardiocirculatory,
      renal, pulmonary, and liver function were unchanged. No case of ACS occurred. In
      the patients undergoing elective abdominal surgery IAP ranged from 6.5+/-2.1 to
      10.0+/-4.0 mmHg. CONCLUSIONS: Fascial closure increased the IAP, which was
      accompanied by short-termed decrease in urine output. At these levels of IAP
      fascial closure appears to be harmless, but further prospective studies are
      needed to determine the critical level of IAP for allowing a safe repair of large
      fascial defects.

PMID- 12209298
TI  - Open mesh plug hernioplasty in ambulatory surgery: a study of feasibility based
      on our experience in 413 procedures.
AB  - This study assessed the feasibility, safety, and reliability of open mesh plug
      hernioplasty under local anesthesia on an ambulatory basis. We retrospectively
      evaluated results using the open mesh plug technique in a series of 398 patients
      with 413 inguinal hernias (378 primary, 35 recurrent). Local anesthesia with
      sedation was used in 91% of procedures, locoregional anesthesia in 8%, and
      general anesthesia in 1%. Median operative time was 45 min. Only 1% of patients
      operated on in ambulatory surgery required hospitalization. There were only mild
      complications, all of which were managed on an outpatient basis. Median time of
      return to work was 8 days. Recurrence rate was 0.83% at a minimal follow-up of 12
      months. Open mesh plug hernioplasty is a reliable technique feasible in an
      outpatient basis.

PMID- 12209299
TI  - Prolene Hernia System compared with Lichtenstein patch: a randomised double blind
      study of short-term and medium-term outcomes in primary inguinal hernia repair.
AB  - BACKGROUND: Refinements in the configuration of mesh may ease handling and
      placement and reduce postoperative discomfort. MATERIAL AND METHODS: A total of
      206 patients were randomly and blindly allocated to receive the Prolene Hernia
      System (PHS) or Lichtenstein patch. Collected data included: surgical incision
      size, procedure time, pain scores, analgesic medication, complications, return to
      activity and work, and quality of life as measured by Short-Form 36 on days 3 and
      14. RESULTS: Immediate post-operative pain was significantly lower with PHS than
      with the patch. The proportion of PHS patients taking longer than 3 days to
      return to normal activity was 15.5%, compared to 28.4% of patch patients.
      Operating time was significantly shorter with PHS (34.1 vs. 38.3 min). There was
      no treatment effect on any of the quality of life scales as measured by Short
      Form 36. There were two recurrences in the patch group. CONCLUSIONS: The study
      indicates a reduction in operating time (4 min) and postoperative recovery with
      the PHS compared with patch.

PMID- 12209300
TI  - Rives-Stoppa procedure for repair of large incisional hernias: experience with 57
      patients.
AB  - BACKGROUND: The use of prosthetic materials in tension-free incisional hernia
      repairs has diminished reherniation rates markedly; however, infection,
      intestinal fistulization, and seroma formation have been reported after repairs.
      Use of the Rives-Stoppa procedure for incisional hernia repair, in which the
      prosthesis is placed between the rectus abdominis muscle and the posterior
      sheath, may reduce occurrence of these problems. METHODS AND MATERIALS: Over a 6
      year period 57 open abdominal wall incisional hernia repairs were performed using
      the Rives-Stoppa technique; 15 (26.3%) had previously undergone incisional hernia
      repair. The prosthetic materials used were polypropylene, expanded
      polytetrafluoroethylene (ePTFE), and ePTFE with perforations. The prosthesis size
      ranged from 8x8 cm to 20x28 cm (mean area 199.6 cm(2)). Follow-up consisted of an
      office visit 12 months postoperatively and at least one subsequent office visit
      or telephone interview; mean follow-up time was 34.9 months (range 11.7-81.9).
      RESULTS: There were no hernia recurrences (except in one patient whose prosthesis
      was removed), gastrointestinal complications, fistulas, or deaths. Seromas
      occurred postoperatively in seven patients (12.3%). Two patients (3.5%) had wound
      infections that required removal of the prosthesis. CONCLUSIONS: In this series
      the Rives-Stoppa technique had excellent long-term results, with minimal
      morbidity, in patients with large primary or recurrent incisional hernias. The
      absence of serious complications and hernia recurrences in patients with grafts
      in place suggests that the Rives-Stoppa procedure is the repair of choice in such
      patients.

PMID- 12209301
TI  - Evaluation of prosthetic mesh closure in semiopen-abdomen patients.
AB  - BACKGROUND: To avoid the adverse consequences of abdominal compartment syndrome
      and to reduce the high mortality the celiotomy wound in patients with abdominal
      sepsis was closed without tension using prosthetic mesh. This produces a semiopen
      situation that permits staged reinterventions together with the functional
      reconstitution of the continuity of the abdominal wall. MATERIAL AND METHODS:
      Twenty-five patients with intra-abdominal sepsis of various causes were evaluated
      retrospectively to assess the results of semiopen management of the septic
      abdomen and reoperations on demand in severe peritonitis. All of the patients
      were in a state of neglected peritonitis, and had at least one failing organ
      system. The Mannheim Peritonitis Index (MPI) scoring system was used for
      stratification of abdominal sepsis. RESULTS: The mean MPI score of 25 patients
      was 24, ranging 10 to 33. Eight (32%) patients were reexplored (MPI=21). There
      were overall 9 (36%) complications in patients with mean MPI score of 23. Six
      (24%) mesh-related complications (infection and enterocutaneous fistulas)
      developed (MPI=19). The mean MPI score of patients without complications was 24.
      Four (16%) patients died with index MPI score of 26 due to fulminant hepatitis,
      myocardial infarction, and multiple organ failure. The admission period averaged
      63 days. CONCLUSIONS: In 25 critically ill patients with abdominal sepsis the
      mortality was lower than expected, relative to heterogeneous data from the
      literature; also, major complications occurred less frequently although the mean
      MPI score was high. The authors conclude that this approach is a reliable
      contribution to the complex treatment of these patients.

PMID- 12209302
TI  - Open mesh versus non-mesh repair of groin hernia: meta-analysis of randomised
      trials based on individual patient data [corrected].
AB  - BACKGROUND: The EU Hernia Trialists Collaboration was established to provide
      reliable evaluation of newer methods of groin hernia repair. It involved 70
      investigators in 20 countries. MATERIALS AND METHODS: Twenty eligible trials
      (5016 participants) of open mesh vs. non-mesh groin hernia repair were
      identified. Meta-analysis was performed using raw individual patient data where
      possible. RESULTS: Fewer hernia recurrences were reported after mesh repair.
      There were no clear differences between mesh and non-mesh groups in
      complications. Overall, those in the mesh groups had a shorter hospital stay,
      quicker return to usual activities and less frequent persisting pain, but
      individual trial results varied. CONCLUSIONS: The review provides strong evidence
      that open mesh repair is associated with a reduction in the risk of recurrence of
      between 50% and 75%. There is also some evidence of quicker recovery and of lower
      rates of persisting pain following open mesh repair.

PMID- 12209303
TI  - Sliding hernias.

PMID- 12209304
TI  - Femoral pseudo-hernias.
AB  - Before surgical intervention in the femoral area, doctors should be mindful of
      two situations in which surgery is not indicated and, in fact, may cause harm.

PMID- 12209305
TI  - Entero-colocutaneous fistula: a late consequence of polypropylene mesh abdominal
      wall repair: case report and review of the literature.
AB  - BACKGROUND: The underlying risk associated with visceral mesh erosion is the
      close opposition of adjacent intestines to the prosthetic graft. This highly
      morbid condition has been described with most types and techniques of abdominal
      wall mesh repair. PATIENT: We report the case of a 52-year-old man who presented
      with an entero-colocutaneous fistula 10 years after prosthetic mesh repair of an
      incisional hernia. The fistula was excised and the abdominal wall defect repaired
      with a tissue-impervious composite. CONCLUSIONS: The use of a tissue-impervious
      barrier avoids development of enteric fistula when a prosthesis is placed
      directly over the viscera.

PMID- 12209306
TI  - Epigastric hernia and its etiology.
AB  - BACKGROUND: Controversies still prevail as to how exactly epigastric hernia
      occurs. Both the vascular lacunae hypothesis and the tendinous fibre decussation
      hypothesis have proved to be widely accepted as possible explanations for the
      etiology. PATIENT: We present a patient who suffered from early-onset epigastric
      hernia. CONCLUSIONS: We believe the identification of the ligamentum teres and
      its accompanying vessel at its fascial defect supports the vascular lacunae
      hypothesis. However, to further our understanding, biopsy of the linea alba in
      patients with epigastric hernias is indicated.

PMID- 12209308
TI  - High fidelity of homologous retroviral recombination in cell culture.
AB  - Genetic variation continues to be a major obstacle in the development of
      therapies and vaccines against retroviral infections and contributes extensively
      to viral pathogenesis and persistence. Recombination is one mechanism that
      increases retroviral variation by shuffling mutations from different genomes.
      Recent studies suggest that recombination not only shuffles the mutations but
      also generates them at high rates during reverse transcription. In contrast to
      these recent studies, this investigation shows that recombination does not
      generate mutations during recombination. A spleen necrosis virus (SNV)-based
      homologous recombination system was used to test the hypothesis that retroviral
      recombination is a high-fidelity process during replication of the virus in cell
      culture. The system consisted of a pair of SNV vectors expressing two drug
      resistance genes. The vectors were constructed so that cells containing
      recombinant proviruses could be selected by a double drug-resistant phenotype.
      Restriction enzyme digestion and agarose gel electrophoresis were used to map the
      location of recombination within 182 proviruses. Sequencing and single-strand
      conformation polymorphism techniques were then used to check for mutations within
      the recombinant proviruses. Since no mutations were detected among the 182
      recombinants that were analyzed, homologous recombination is a high-fidelity
      process for retroviruses in cell culture.

PMID- 12209309
TI  - Coccolithovirus (Phycodnaviridae): characterisation of a new large dsDNA algal
      virus that infects Emiliana huxleyi.
AB  - Emiliania huxleyi-specific viruses ( EhV) were isolated from E. huxleyi blooms
      off the coast of Plymouth, UK, in July 1999 and July/August 2001, and from an E.
      huxleyi bloom induced during a mesocosm experiment in a fjord off Bergen, Norway,
      during June 2000. Transmission electron microscopy revealed that all 10 virus
      isolates are 170-200 nm in diameter with an icosahedral symmetry. Their density
      is approximately 1.2 in CsCl gradients and they have large double stranded DNA
      genomes approximately 410 kb in size. Phylogenetic analysis of the DNA polymerase
      genes of these viruses suggests that EhV belongs to a new genus within the family
      of algal viruses, Phycodnaviridae. We propose to name this new virus genus
      Coccolithovirus. Differences within members of the Coccolithovirus were
      elucidated by host range analysis of the virus isolates and sequence analysis of
      a gene fragment encoding part of their putative major capsid protein. All 10
      virus isolates within this new genus only infected E. huxleyi strains that have
      previously been shown to exhibit low dimethylsulphoniopropionate lyase (DMSP
      lyase) activity (CCMP1516, CCMP374 and L), while E. huxleyi strains with high
      DMSP-lyase activity (CCMP373 and CCMP379) were resistant to infection.

PMID- 12209310
TI  - Sequence analysis of genome segments S4 and S8 of Mal de Rio Cuarto virus (MRCV):
      evidence that the virus should be a separate Fijivirus species.
AB  - This is the first sequence-based characterization of Mal de Rio Cuarto virus
      (MRCV), currently classified as a variant of Maize rough dwarf virus (MRDV) and
      exclusively found in South America. We sequenced and analyzed genome segments S4
      and S8. MRCV S4 coded for a putative 131.67 kDa protein while MRCV S8 coded for a
      putative 68.26 kDa protein containing an ATP/GTP-binding motif. The 5' and 3'
      ends of MRCV segments, were 5'AAGUUUUU3' and 5'CAGCUnnnGUC3', respectively.
      Prediction of secondary structure of both segments coding strands showed that
      terminal regions were able to form structures that are proposed to be replication
      and packaging signals. MRCV S4 showed identity to members of Fijivirus as well as
      to two other genera of the Reoviridae family. MRCV S8 revealed identity with Rice
      black streaked dwarf virus (RBSDV) S8, MRDV S7, Oat sterile dwarf virus (OSDV) S9
      and Nilaparvata lugens reovirus (NLRV) S7. While MRDV and RBSDV segments are
      highly homologous between each other, MRCV identity levels with them was
      considerably lower. We discussed the evolutionary relationships of MRCV to other
      Reoviridae, and based on phylogenetic analysis we proposed that although MRCV is
      related to MRDV, it could be regarded as a new species of the Fijivirus genus.

PMID- 12209311
TI  - PCR-RFLP based molecular typing of enteroviruses isolated from patients with
      aseptic meningitis in Korea.
AB  - We have evaluated PCR-RFLP as a practical method for rapid typing of
      enteroviruses causing aseptic meningitis in Korea. Through blind examination of
      80 clinical isolates from patients with aseptic meningitis, we have compared the
      results of conventional serotyping with PCR-RFLP based genotyping, which was
      developed for this study. Among the 80 case isolates, which had been previously
      typed by routine neutralization test, only 42 cases (52.5%) were matched with
      typing by PCR-RFLP. The result clearly demonstrated that the enterovirus serotype
      does not coincide with the genotype. Therefore, the classification of
      enteroviruses by genotyping with PCR-RFLP, although rapid and simple, may be
      complicated by regional or seasonal differences. However, the PCR-RFLP method
      developed in this study is applicable to the epidemiological study of
      enteroviruses when regional or seasonal differences exist, and is useful in
      identifying the source of an infection.

PMID- 12209312
TI  - Measles virus enhances the expression of cellular immediate-early genes and DNA
      binding of transcription factor AP-1 in lung epithelial A549 cells.
AB  - In this work we investigated the effect of measles virus (MV) infection on the
      expression of immediate-early genes junB, c-jun and c-fos mRNA as well as AP-1
      DNA-binding activity in the lung epithelial-like adenocarcinoma cell line A549.
      The transcription factor AP-1, which is a group of dimeric complexes of the Fos
      and Jun family proteins, is an important regulator in many cellular responses to
      different extracellular stimuli. Membrane cofactor protein CD46, which acts as a
      receptor for laboratory-adapted and vaccine strains of MV, has been reported to
      associate with beta1 integrin molecules, which are known to trigger signaling
      events and activate immediate-early genes. The expression of junB and c-jun mRNA
      was rapidly induced by MV. It was observed already at 1 h postinfection and
      detected again at the later phase of infection. Moreover, the expression of c-fos
      mRNA seemed to be weak and transient. The early induction was apparently
      associated with MV binding and CD46 clustering, whereas the later induction
      coincided with virus replication. MV infection also enhanced the activation of AP
      1 DNA-binding. Our results suggest that changes in the expression of immediate
      early genes and in the activation of AP-1 DNA-binding may have an important role
      in many cellular events detected in MV-infected cells.

PMID- 12209313
TI  - Expression of immunoreactive forms of the hepatitis C NS5A protein in E. coli and
      their use for diagnostic assays.
AB  - In this study different forms of the hepatitis C virus (HCV) NS5A protein,
      including a nearly full-length, an amino-terminal and a carboxy-terminal
      truncated form were produced in E. coli as fusion proteins with the MBP or the
      GST protein. The chimeric proteins were tested for their reactivity with sera
      from HCV infected patients by immunoblot and ELISA assays. A panel of 110 sera
      specimens, including 39 HCV-positive sera, 27 sera from patients with non-HCV
      associated liver disease and 44 healthy individuals were analyzed for the
      presence of antibodies to NS5A. Twenty four (61 %) out of the 39 HCV positive
      sera, showed reactivity against the nearly full length NS5A, 21 (54 %) against
      the amino-terminal part of NS5A and 20 (51 %) against the carboxy-terminal part
      of the NS5A protein in immunoblot assays, suggesting that immunoreactive epitopes
      are present both at the carboxy- and the amino- terminal part of the protein.
      None of the 71 HCV-negative serum samples showed any reactivity against the NS5A
      antigens. With the exception of one patient, similar data were obtained with an
      ELISA assay based on the use of the nearly full-length NS5A antigen. The data
      indicate that new forms of NS5A may be potentially valuable antigens for the
      development of serological assays for HCV.

PMID- 12209314
TI  - The efficacy of a DNA vaccine encoding herpes simplex virus type 1 (HSV-1)
      glycoprotein D in decreasing ocular disease severity following corneal HSV-1
      challenge.
AB  - Antiviral effects of a DNA vaccine against herpes simplex virus 1 (HSV-1)
      glycoprotein D (gD) were evaluated in eight week-old female BALB/c mice. The
      nuclease-insensitive construct (gD-ASOR) consisted of an HSV-1 gD encoding
      plasmid coupled to asialo orosomucoid (ASOR), targeting it to cells bearing ASOR
      receptors. Mice were immunized on day 0 and 7 with 10 microg doses of gD-ASOR or
      control substances. Fourteen days later, mice were infected by the corneal route
      with 10(5) pfu or 10(6) pfu HSV-1, strain 17syn+. Immunized mice showed a
      significant decrease in ocular disease severity over a 21-day observation period
      following infection compared to sham-immunized mice. Acute replication kinetic
      assays demonstrated a 100-fold decrease in viral titers on day 6 in trigeminal
      ganglia from immunized BALB/c mice compared to sham-immunized mice. Immunized
      mice showed a significant increase in numbers of CD4(+)T cells infiltrating the
      trigeminal ganglia at day 6 post infection compared to sham-immunized mice.
      Significant differences were not seen in latent viral reservoir between immunized
      and unimmunized mouse groups. Immunization with gD-ASOR decreased the severity of
      acute ocular HSV-1 infection, induced a CD4(+) T cell response, decreased the
      viral load in the trigeminal ganglia, but did not diminish viral latency.

PMID- 12209315
TI  - Analysis of conserved and non-conserved amino acids critical for ALSV (Avian
      leukemia and sarcoma viruses) integrase functions in vitro.
AB  - Retroviral integrase (IN) is the viral enzyme responsible for the integration of
      viral DNA into host cellular DNA. In vitro, recombinant IN protein is able to
      catalyze the 3'-processing, strand transfer and disintegration activities. In
      order to analyze the importance of specific residues of ALSV (Avian leukemia and
      sarcoma viruses) IN protein, we introduced 31 amino acid substitutions either in
      residues previously shown by others to be involved in IN oligomerization or in
      selected conserved and non-conserved residues through the IN sequence. We tested,
      in vitro, the three catalytic activities of these mutants as well as their
      capacity to bind DNA. We found that (i) 88% of the substitutions occurring on
      well-conserved residues have an effect on IN activities (ii) two mutants (S85T in
      the central catalytic domain and N197C in the C-terminal domain) present a
      reduced efficiency of DNA binding compared to the wild type protein. Moreover,
      all mutations made on the dimer interface of C-terminal domain present reduced
      activities, suggesting an important role of this part of the protein. Finally,
      for some mutations, we observed differences between the ALSV and HIV (Human
      immunodeficiency virus) IN corresponding residues.

PMID- 12209316
TI  - Classical swine fever virus NS5B-GFP fusion protein possesses an RNA-dependent
      RNA polymerase activity.
AB  - RNA-dependent RNA polymerase (RdRp) is the replicase of positive-strand RNA
      viruses. Expression and characterization of the replicase are the first steps in
      the elucidation of the virus replication mechanism. We expressed nonstructural
      protein 5B (NS5B) of classical swine fever virus (CSFV) as a fusion protein with
      green fluorescent protein (GFP) in porcine kidney cells (PK-15 cells), natural
      host cells of CSFV. The expressed CSFV NS5B-GFP fusion protein possessed RdRp
      activity. By fluorescence microscope it was observed that the density of the
      fusion protein near cytoplasmic membranes was higher than that in other parts of
      cells. This was in contrast to the distribution of the GFP alone which was
      uniformly distributed throughout the cytoplasm. The GFP is a signal for the
      location of NS5B in a host cell that allows in vitro and in vivo investigation of
      the distribution of plus-strand RNA virus RdRp.

PMID- 12209317
TI  - The relationship between Pepper mottle virus source leaf and spread of infection
      through the stem of Capsicum sp.
AB  - Pepper mottle virus (PepMoV) systemically infects Capsicum sp. in a typical
      source-to-sink manner with movement through the stem occurring in a predictable
      pattern. This study was carried out to determine the relationship between the
      inoculated leaf as a source of inoculum and the spread of PepMoV infection
      through the stem. C. annuum 'Early Calwonder' plants were mechanically inoculated
      onto the first leaf with PepMoV and sets of 30 plants had their inoculated leaves
      removed each day from 1 through 7 days post-inoculation (dpi) with the inoculated
      leaves tested for infection by ELISA at the time of excision. Beginning at 2 dpi,
      PepMoV infection in the stem of plants with the inoculated leaf excised and
      plants of a nonexcision control treatment was determined using immuno-tissue blot
      analysis. PepMoV was detected in inoculated leaves beginning at 3 dpi with the
      percentage of infected leaves increasing each day through 7 dpi. PepMoV was first
      detected in the stem of inoculated plants of the 3 dpi excision treatment. The
      accumulation and extent of spread of infection in the stem was similar for plants
      that had their inoculated leaf removed at a time preceding detection by ELISA to
      plants in the nonexcision control treatment. These findings suggest that once
      virus is allowed to enter the stem from the inoculated leaf, subsequent spread of
      infection through the stem is a process independent from the source leaf.

PMID- 12209318
TI  - Isolation of differentially expressed genes from white spot virus (WSV) infected
      Pacific blue shrimp (Penaeus stylirostris).
AB  - To isolate novel cellular factors that are activated or repressed upon WSV
      infection, the RNA fingerprints of healthy and WSV infected blue shrimp ( Penaeus
      stylirostris) were compared using the mRNA differential display technique. Thirty
      two unique differentially expressed, and one constitutively expressed, cDNA
      sequences were retrieved. Six of 32 cDNAs showed similarities with the database
      entries: cDNA 10G32-142 to a shrimp arginine kinase, 22C48-201 to shrimp
      mitochondrial ATPase gene; 22C47-197, 21G49-203 and 20A55-268 to shrimp ESTs and
      20G50-206 to a WSV gene, ORF 116. The constitutively expressed gene showed
      significant similarity to a yeast elongation factor 1-alpha gene. The expression
      of a subset of differentially expressed genes (13 of 32) was further evaluated by
      real-time RT-PCR. Ten of 13 genes showed statistically significant changes in
      expression between healthy and WSV infected animals suggesting that these genes
      may play an important role in WSV pathogenesis.

PMID- 12209319
TI  - A non-aphid-transmissible isolate of bean yellow mosaic potyvirus has an altered
      NAG motif in its coat protein.
AB  - An isolate of Bean yellow mosaic virus (BYMV) not transmitted by aphids (NAT) was
      compared with the aphid-transmissible isolate (MI) from which it was derived. For
      each isolate, the sequence of the coat protein and parts of the helper component
      was determined. A single nucleotide substitution caused a NAG to NAS alteration
      in the coat protein of the non aphid-transmissible isolate. Loss of aphid
      transmissibility in isolate BYMV(MI)-NAT was most likely caused by this mutation
      within the NAG motif. Systemic movement and accumulation of the virus in infected
      plants were not affected by the mutation.

PMID- 12209320
TI  - Identification of human astrovirus infections from stool samples with diarrhea in
      Korea.
AB  - Human astrovirus (HAstV) infections were confirmed in 17 (1.5%) of 1153 children
      and adults with diarrhea, from different regions of Korea, by testing their stool
      samples by reverse transcription-polymerase chain reaction using primers targeted
      to partial ORF 1a. Genotypes of isolates were determined by sequencing the 289-bp
      PCR products. The predominant genotype was HAstV type 1, with intragenotypic
      variation of 0.7%. Unlike Norwalk-like viruses (NLVs), rotavirus and enteric
      adenovirus, no data on HAstV have been reported in association with diarrhea in
      Korea. The incidence of HAstV infection reported in this study indicates that
      HAstV is one of the viral agents causing gastroenteritis in Korea, and that a
      continuous molecular epidemiological study of HAstV infection is required.

PMID- 12209322
TI  - The family Tymoviridae.
AB  - The family Tymoviridae comprises the genus Tymovirus, from which it derives its
      name, the genus Marafivirus and the newly established genus Maculavirus. Members
      of the family share the following characteristics: (i) non-enveloped isometric
      particles c. 30 um in diameter, with a rounded contour and prominent surface
      structures, and clustering of coat protein subunits in pentamers and hexamers;
      (ii) the presence in preparations of purified virus particles of two centrifugal
      components, made up of non-infectious protein shells (T) that may contain small
      amounts of RNA (primarily subgenomic coat protein mRNA) and of infectious
      nucleoproteins (B), that contain the virus genome; (iii) possession of a positive
      sense, single-stranded RNA genome with an unusually high cytidine content (32 to
      c. 50%), capped at the 5' terminus and containing a very large ORF encodes
      replication-related proteins analogous to those of other taxa of the "alpha-like"
      supergroup of ssRNA viruses; (iv) a replication strategy possibly encompassing
      posttranslational proteolytic cleavage of the polypeptide encoded by ORF1 by a
      papain-like virus-encoded protease, and coat protein expression via a subgenomic
      RNA; (v) the presence in infected cells of cytopathic structures, thought to be
      the sites of RNA replication, originating from severely altered chloroplasts
      and/or mitochondria, the periphery of which is lined with vesicles produced by
      the localized invaginations of the bounding membrane. There are 23, 4, and 2
      known species in the genera Tymovirus, Marafivirus and Maculavirus, respectively.
      The genus Marafivirus also contains one tentative species.

PMID- 12209321
TI  - Molecular epidemiology of hepatitis B virus in Afro-Venezuelan populations.
AB  - Hepatitis B virus (HBV) infection among Venezuelan populations of African origin
      was analyzed. These populations exhibited lower HBV prevalence than the one found
      in the African continent. Sequence analysis of 6 isolates showed that 3 belonged
      to genotype F, while the 3 others were HBV genotype A. HBV genotype A was more
      common in the Afro-Venezuelan groups than in the general Venezuelan population.
      This might reflect the introduction of genotype A during the slavery period. The
      absence of the African genotype E among these isolates supports the hypothesis of
      a recent origin for this HBV genotype. HBV genotype F has already been introduced
      to these relatively isolated communities.

PMID- 12209323
TI  - Maculavirus, a new genus of plant viruses.
AB  - Maculavirus is a new genus of plant viruses typified by Grapevine fleck virus
      (GFkV). A possible second member is Grapevine redglobe virus (GRGV).
      Maculaviruses are phloem-limited non-mechanically transmissible viruses with
      isometric particles c. 30 nm in diameter that have a rounded contour and
      prominent surface structure. Vectors, if any, are unknown. GFkV preparations
      contain two centrifugal components, T made up of empty protein shells and B,
      which contains 35% RNA. The coat protein (CP) has a molecular mass of 24 kDa. The
      genome is a single-stranded RNA that has c. 50% cytosine residues. It is 7564 nt
      in size, excluding the poly(A) tail and contains four putative open reading
      frames (ORF) that encode a 215.4 kDa polypeptide with the conserved motifs of
      replication-associated proteins of positive-strand RNA viruses (ORF1), the CP
      (ORF2), and one (GRGV) or two (GFkV) proline-rich polyproteins of 31.4 kDa (ORF3)
      and 15.9 kDa (ORF4), respectively, with unknown function. Replication-associated
      proteins and CP are phylogenetically related to those of members of the genera
      Tymovirus and Marafivirus. GFkV-infected grapevine cells contain vesiculated
      mitochondria, the possible site of RNA replication. In the natural host, GFkV
      particles accumulate in great quantity, sometimes in crystalline arrays in phloem
      cells.

PMID- 12209324
TI  - Early scheduled laparoscopic cholecystectomy following percutaneous transhepatic
      gallbladder drainage for patients with acute cholecystitis.
AB  - AIM: The present study was conducted to evaluate the effectiveness of early
      scheduled laparoscopic cholecystectomy (LC) following percutaneous transhepatic
      gallbladder drainage (PTGBD) for patients with acute cholecystitis. PATIENTS AND
      METHODS: 31 patients with acute cholecystitis were treated by early scheduled LC
      following PTGBD (group 1). These patients were compared with 9 patients treated
      by early LC without PTGBD (group 2) and with 12 patients treated by delayed LC
      following conservative therapy (group 3) for the success rate of intraoperative
      cholangiography, the conversion rate to open cholecystectomy, operative time, and
      hospital stay. Early scheduled LC following PTGBD was defined as scheduled LC
      when the patient's condition recovered and it was performed 1-7 days (mean: 4
      days) after admission. The patients' age in group 1, 2, and 3 was 66 +/- 13, 65
      +/- 10, and 64 +/- 9 years, respectively, without significant difference. Most of
      the patients had additional diseases. RESULTS: The success rate of intraoperative
      cholangiography was 97% (30/31) in group 1, 67% (6/9) in group 2, and 67% (8/12)
      in group 3. The conversion rate to open cholecystectomy was 3% (1/31) in group 1,
      33% (3/9) in group 2, and 33% (4/12) in group 3. The operative time for LC was 89
      +/- 33 min in group 1, 116 +/- 24 min in group 2, and 135 +/- 30 min in group 3.
      The mean hospital stay after LC was 9 +/- 4 days in group 1, 9 +/- 3 days in
      group 2, and 17 +/- 7 days in group 3. In group 1, the success rate of
      intraoperative cholangiography was higher, the conversion rate to open
      cholecystectomy was lower, and operative time was shorter than in groups 2 and 3
      with significant difference (p <0.05, p <0.05, and p <0.01, respectively).
      CONCLUSION: The findings of this study indicate that early scheduled LC following
      PTGBD is a safe and effective therapeutic option for patients with acute
      cholecystitis especially in elderly and complicated patients.

PMID- 12209325
TI  - Postoperative complications after laparoscopic incisional hernia repair.
      Incidence and treatment.
AB  - BACKGROUND: The popularity of laparoscopic repair of incisional hernias is
      increasing due to the apparent advantages of laparoscopy. PATIENTS AND METHODS: A
      group of 150 consecutive patients with incisional hernias were treated by
      laparoscopic IPOM technique with a Goretex Dualmesh between September 1999 and
      September 2001 and subsequently followed up. Some minor and major complications
      could clearly identify advantages as well as drawbacks of the technique. RESULTS:
      No primary mesh infection were observed but 4 recurrences, 3 of them due to
      technical mistakes, and 1 case with ileus due to a volvolus at day 4 p.o. were
      recorded. Further major complications included 2 early and 2 later stage trocar
      hernias, which needed surgical correction. Two patients developed secondary bowel
      perforation after thermal injury and after primary enterotomy which was closed by
      laparotomy. CONCLUSIONS: All complications, except one recurrence due to failure
      of the material, were surgical mistakes and cannot be attributed to the
      laparoscopic procedure. Consequently, after taking into account the surgical
      mistakes and possible technical errors, the low recurrence rate justifies further
      application of laparoscopic ventral hernia repair.

PMID- 12209326
TI  - Elemental composition of acidocalcisomes of Trypanosoma cruzi bloodstream
      trypomastigote forms.
AB  - The elemental composition of acidocalcisomes present in Trypanosoma cruzi
      bloodstream trypomastigotes was analyzed by X-ray microanalysis. Acidocalcisomes
      appear as electron-dense vesicles dispersed throughout the cytoplasm. X-ray
      microanalysis of whole cells adhered to Formvar-coated grids showed that they
      contained C, O, Na, Mg, P, S, Ca and Zn, although in some acidocalcisomes iron
      was also detected. However, in ultra-thin sections of parasites processed
      according to routine procedures, most elements were lost. Living parasites were
      incubated with gold-labeled holo-transferrin to test if the iron was taken up by
      receptor-mediated endocytosis. After incubation at 4 degrees C, labeling was
      observed only in the flagellar pocket membrane, showing that receptors to this
      protein are already present in bloodstream trypomastigotes. In parasites
      incubated at 28 degrees C no intracellular tracer was observed, despite the
      labeling in the flagellar pocket membrane. Our data show that some
      acidocalcisomes of T. cruzi bloodstream trypomastigotes contain iron and that
      this element was not taken up by receptor-mediated endocytosis.

PMID- 12209327
TI  - Purification of Taenia solium cysticerci superoxide dismutase and myoglobin
      copurification.
AB  - Superoxide dismutase from Taenia solium cysticerci ( Ts SOD) was purified by
      sequential ion exchange chromatography on quaternary-amino-ethyl-cellulose (QAE)
      followed by hydrophobic interaction on phenyl sepharose (PS) and chromatofocusing
      on a polybuffer exchanger 94 (PBE). Ts SOD is a 30 kDa molecular weight dimeric
      enzyme with 15 kDa monomers. It is partially negative, hydrophilic, with 6.3
      isoelectric point and has 2,900 U/mg activity. Bovine erythrocyte SOD antibodies
      cross react with Ts SOD. This enzyme is 80% inhibited by 10 mM of KCN suggesting
      that it has a Cu/Zn active site. Furthermore, Ts SOD totally loses its activity
      at 100 degrees C for 4 min. The first 25 amino acids from the Ts SOD N-terminal
      are (M K A V X V M R G E E G V K G V V H F T Q A G D A). This sequence is 76%
      similar to the Schistosoma mansoni Cu/Zn SOD. By chance, myoglobin (Mb) was also
      found during the purification process. A 16 kDa band was recognized in
      immunoblotting by horse heart Mb antibodies in QAE, PS and PBE, the last
      mentioned being found at pH 7.0. The first 15 amino acids from the amino terminal
      group (G L S D G E W Q L V L N V W G) in this 16 kDa protein are identical to
      several other Mbs which have been reported.

PMID- 12209328
TI  - Mast-cell-dependent histamine release after praziquantel treatment of Schistosoma
      japonicum infection: implications for chemotherapy-related adverse effects.
AB  - As previously shown, the development of adverse effects in praziquantel treatment
      of Schistosoma japonicum infection involves host anaphylactic reactions
      associated with a rapid elevation of the level of plasma histamine. This study,
      using genetically mast-cell-deficient mice, aimed at identifying the major source
      of plasma histamine released after praziquantel treatment. Mast-cell-deficient
      mice and congenic normal mice were treated with praziquantel 8 weeks after
      infection with S. japonicum. In normal congenic mice, the plasma histamine level
      at 60 min after chemotherapy was substantially higher (mean+/-SD: 123.34+/-23.13
      ng/ml) than that in mast-cell-deficient mice (7.02+/-3.48 ng/ml). These results
      show that mast cells play a predominant role in the rapid increase of the plasma
      histamine level. Despite their lack of increase in plasma histamine, mast-cell
      deficient mice exhibited post-praziquantel systemic signs but not histopathologic
      alterations due to allergic reactions, suggesting that unidentified mechanism(s)
      also contribute to the development of adverse post-praziquantel effects.

PMID- 12209329
TI  - Blood culture and polymerase chain reaction for the diagnosis of the chronic
      phase of human infection with Trypanosoma cruzi.
AB  - In the present study, we evaluated for the first time the profile of blood
      parasitism in untreated, chronic Chagas' disease. The study was conducted on 60
      patients and a control group of nine serologically negative individuals. Analysis
      of three blood samples showed 70% cumulative positivity for blood culture and
      86.7% positivity for PCR. The comparison of the two tests revealed that 41.1%
      (74/180) of the samples presented positive results for both PCR and blood
      culture, 22.2% (40/180) were positive for PCR alone, and 4.4% (8/180) were
      positive for blood culture and negative for PCR. The addition of the second
      sample raised positivity significantly for both blood culture ( P=0.0000) and PCR
      ( P=0.0369). Addition of the third sample was also statistically significant for
      blood culture ( P=0.0001) but not for PCR ( P=0.1186). These data point to the
      importance of studying the parasitemia of Trypanosoma cruzi-infected individuals
      before specific treatment. They also suggest that at least two blood samples
      should be collected and that two tests should be used, if possible--a procedure
      that considerably improves the parasitologic diagnosis of Chagas' disease and the
      evaluation of therapeutic efficacy.

PMID- 12209330
TI  - Do interleukin-6 and macrophage-migration inhibitory factor play a role during
      sex-associated susceptibility in murine cysticercosis?
AB  - In murine Taenia crassiceps cysticercosis, females sustain larger intensities of
      infection than males. However, during chronic infection, this difference
      disappears and males show a feminization process. To further study the role of
      two cytokines, interleukin-6 (IL-6) and macrophage-migration inhibitory factor
      (MIF), known to be involved in immunoendocrinological processes during sex
      associated susceptibility in cysticercosis, IL-6 and MIF gene knockout (KO) mice
      were infected, and the number of parasites and serum sex-steroid levels were
      measured. Results show that IL-6 and MIF KO mice of both genders infected with T.
      crassiceps cysticerci harbor similar numbers of parasites, with no change in sex
      hormone levels. However, in wild-type strains, females have twice as many
      parasites as males. At the same time, there is a decrease of 80% in testosterone
      and dihydrotestosterone serum levels, and a 100-fold increase in the levels of
      estradiol in infected male mice. These results suggest a role for both IL-6 and
      MIF genes in sex-associated susceptibility in murine T. crassiceps cysticercosis.

PMID- 12209331
TI  - Ectonucleotide diphosphohydrolase activity in Crithidia deanei.
AB  - In this work we describe the ability of living Crithidia deanei to hydrolyze
      extracellular ATP. In intact cells at pH 7.2, a low level of ATP hydrolysis was
      observed in the absence of any divalent metal (0.41+/-0.13 nmol P(i) h(-1) 10(7)
      cells(-1)). The ATP hydrolysis was stimulated by MgCl(2) and the Mg(2+)-dependent
      ecto-ATPase activity was 4.05+/-0.17 nmol P(i) h(-1) 10(7) cells(-1). Mg(2+)
      dependent ecto-ATPase activity increased linearly with cell density and with time
      for at least 60 min. The addition of MgCl(2) to extracellular medium increased
      the ecto-ATPase activity in a dose-dependent manner. At 5 mM ATP, half-maximal
      stimulation of ATP hydrolysis was obtained with 0.93+/-0.26 mM MgCl(2). This
      stimulatory activity was also observed when MgCl(2) was replaced by MnCl(2), but
      not CaCl(2) or SrCl(2). The apparent K(m) for Mg-ATP(2-) was 0.26+/-0.03 mM. ATP
      was the best substrate for this enzyme; other nucleotides, such as ITP, GTP, UTP
      and CTP, produced lower reaction rates. In the pH range from 6.6 to 8.4, in which
      the cells were viable, the acid phosphatase activity also present in this cell
      decreased, while the Mg(2+)-dependent ATPase activity did not change. This ecto
      ATPase activity was insensitive to inhibitors of other ATPase and phosphatase
      activities, such as oligomycin, sodium azide, bafilomycin A(1), ouabain,
      vanadate, molybdate, sodium fluoride and tartrate. To confirm that this Mg(2+)
      dependent ATPase was an ecto-ATPase, we used the impermeant inhibitor 4, 4'
      diisothiocyanostylbene 2'-2'-disulfonic acid as well as suramin, an antagonist of
      P(2) purinoreceptors and inhibitor of some ecto-ATPases. These two reagents
      inhibited the Mg(2+)-dependent ATPase activity in a dose-dependent manner. The
      cell surface location of the ATP-hydrolyzing site was also confirmed by
      cytochemical analysis.

PMID- 12209332
TI  - Behavioural dominance and Taenia crassiceps parasitism in BALB/c male mice.
AB  - Behavioural dominance relationships in mouse populations are based upon fighting
      and antagonistic behaviour. Social rank is affected by the physiological states
      present in the mice. Experimental infection by Taenia crassiceps cysticerci
      induced physiological disorders and disrupted the dominant-subordinate status.
      Infected male mice showed strong perturbations in territorial behaviour and
      aggressiveness. Infected dominant male mice did not show a significant reversal
      of dominance order compared to uninfected mice. In addition, during confrontation
      between naive infected and healthy mice, infected animals more often assumed a
      subordinate status than healthy ones. The effects of the infection by T.
      crassiceps were more likely to prevent adult male mice from becoming
      behaviourally dominant than to reverse existing dominance relationships. The
      results are discussed on the basis of the parasite manipulation hypothesis and
      host optimal foraging and decision-making theories.

PMID- 12209333
TI  - Polymorphism analysis of the internal transcribed spacer and small subunit of
      ribosomal RNA genes of Leishmania mexicana.
AB  - Leishmania mexicana causes a wide spectrum of clinical diseases. In spite of the
      variety of clinical forms, no data exist regarding genetic polymorphism of L.
      mexicana. We analyzed the polymorphism of the internal transcribed spacer (ITS)
      and the small subunit rRNA genes of 3 reference strains and 24 Mexican isolates
      of L. mexicana, by means of polymerase chain reaction and subsequent digestion by
      restriction enzymes. All strains of L. mexicana had invariant patterns for both
      the ITS and the small subunit of rRNA genes. Leishmania amazonensis and
      Leishmania venezuelensis displayed polymorphism only in the ITS. The high degree
      of identity of this region was confirmed by sequencing DNA from three L. mexicana
      isolates. There was almost complete identity of the sequence for the ITS region
      of L. venezuelensis and that of strains of Leishmania major, suggesting that
      these species may be more closely related than previously thought.

PMID- 12209334
TI  - A single genotype of Encephalitozoon intestinalis infects free-ranging gorillas
      and people sharing their habitats in Uganda.
AB  - Microsporidian spores have been detected by Chromotrope 2R and calcofluor stains
      in fecal samples of three free-ranging human-habituated mountain gorillas in
      Uganda and in two people who share gorilla habitats. All spore isolates have been
      identified by PCR with species-specific primers and fluorescent in situ
      hybridization with a species-specific oligonucleotide probe to be Encephalitozoon
      intestinalis. Sequencing analyses of the full length SSUrRNA amplified from all
      spore isolates were identical with Enc. intestinalis SSUrRNA GenBank SIU09929.
      Sequences generated from a fragment containing the internal transcribed spacer of
      these isolates were identical to GenBank sequence Y11611, i.e., Enc. intestinalis
      of anthroponotic origin. A single pathogen genotype in two genetically distant
      but geographically united host groups indicates anthropozoonotic transmission of
      Enc. intestinalis. It is highly unlikely that these two identical Enc.
      intestinalis genotypes were acquired independently by gorillas and people; it is
      much more probable that one group initiated infection of the other.

PMID- 12209335
TI  - Histodytes microocellatus gen. et sp. nov. (Dracunculoidea: Guyanemidae), a
      parasite of Raja microocellata on the European Atlantic coast (north-western
      Spain).
AB  - We describe a new genus, Histodytes, within the family Guyanemidae (Nematoda:
      Spirurida: Camallanina: Dracunculoidea). The type species, Histodytes
      microocellatus n. sp., is found in the gill, heart, kidney, spleen and gonad
      tissues of Raja microocellata from the continental shelf off the estuary of Muros
      y Noia (north-western Iberian Peninsula). Histodytes differs morphologically from
      the three other genera described to date in this family ( Guyanema,
      Travassosnema, Pseudodelphys) because the vulva is situated a long way back from
      the oesophageal-intestinal union, and the anterior uterine branch almost reaches
      to the level of this union. In addition, it can be distinguished from Guyanema
      and Travassosnema by the absence of caudal alae in the male, and from
      Travassosnema by the much greater length of the glandular oesophagus and the lack
      of an oesophageal appendix. Histodytes is the only guyanemid genus described to
      date from an elasmobranch and the first one to be found on the European Atlantic
      coast.

PMID- 12209336
TI  - Dose-dependent egg excretion in foxes ( Vulpes vulpes) after a single infection
      with Toxocara canis eggs.
AB  - Faecal egg counts were performed daily for a period of 4 months on six silver fox
      cubs inoculated individually with an egg dose of 30, 100, 300, 1,000, 3,000, or
      20,000 Toxocara canis eggs. At the lowest and the highest dose levels, the cubs
      did not develop patent infections. In the remaining cubs, the initial appearance
      of eggs in the faeces occurred 35-38 days post-infection (DPI), the patency
      period varied between 8 and 72 days, and the maximal EPG ranged from 980 to 5,700
      (39-85 DPI). The highest egg excretion rates were found in cubs inoculated with
      300 and 1,000 eggs. This study demonstrates that T. canis egg excretion rate in
      fox cubs is not linearly correlated with the ingestion level.

PMID- 12209337
TI  - Helminth fauna of the racoon dog (Nyctereutes procyonoides Gray, 1834) in
      Belorussian Polesie.

PMID- 12209338
TI  - Acid phosphatase activity in excretion/secretion products from Heligmosomoides
      polygyrus adults: an indicator of the physiological status of the worms.
AB  - Acid phosphatase (AP) activity was detected in 24 h culture media from adult
      Heligmosomoides polygyrus. Female and male excretion/secretion products showed
      similar specific activity. For both, the AP had a pH optimum of 4.0 and was
      inhibited by sodium fluoride, tartaric acid, and sodium orthovanadate. The
      release of AP by adult worms was significantly inhibited by adverse incubation
      conditions (temperatures of 20 degrees C and 4 degrees C), known physiological
      perturbers ( t-butylhydroperoxide and sodium azide), and broad spectrum
      anthelmintics (albendazole, levamisole, morantel, and ivermectin). These results
      indicate that the AP activity level in the culture medium may be an indicator of
      the physiological status of the worms.

PMID- 12209339
TI  - Discrimination of coloured patterns by honeybees through chromatic and achromatic
      cues.
AB  - We investigated pattern discrimination by worker honeybees, Apis mellifera,
      focusing on the roles of spectral cues and the angular size of patterns. Free
      flying bees were trained to discriminate concentric patterns in a Y-maze. The
      rewarded pattern could be composed of either a cyan and a yellow colour, which
      presented both different chromatic and achromatic L-receptor contrast, or an
      orange and a blue colour, which presented different chromatic cues, but the same
      L-receptor contrast. The non-rewarded alternative was either a single-coloured
      disc with the colour of the central disc or the surrounding ring of the pattern,
      a checkerboard pattern with non-resolvable squares, the reversed pattern, or the
      elements of the training pattern (disc or ring alone). Bees resolved and learned
      both colour elements in the rewarded patterns and their spatial properties. When
      the patterns subtended large visual angles, this discrimination used chromatic
      cues only. Patterns with yellow or orange central discs were generalised toward
      the yellow and orange colours, respectively. When the patterns subtended a visual
      angle close to the detection limit and L-receptor contrast was mediating
      discrimination, pattern perception was reduced: bees perceived only the pattern
      element with higher contrast.

PMID- 12209340
TI  - Lateral line reception in still- and running water.
AB  - The lateral line of fish is composed of neuromasts used to detect water motions.
      Neuromasts occur as superficial neuromasts on the skin and as canal neuromasts in
      subepidermal canals. Fibres of the lateral line nerves innervate both. There have
      been extensive studies on the responses of lateral line nerve fibres to dipole
      stimuli applied in still water. However, despite the fact that many fish live in
      rivers and/or swim constantly, responses of lateral line nerve fibres to dipole
      stimuli presented in running water have never been recorded. We investigated how
      the peripheral lateral line of still water fish ( Carassius auratus) and riverine
      fish ( Oncorhynchus mykiss) responds to minute sinusoidal water motions while
      exposed to unidirectional water flow. Both goldfish and trout have two types of
      posterior lateral line nerve fibres: Type I fibres, which most likely innervate
      superficial neuromasts, were stimulated by running water (10 cm s(-1)). The
      responses of type I fibres to water motions generated by a vibrating sphere were
      masked if the fish was exposed to running water. Type II fibres, which most
      likely innervate canal neuromasts, were not stimulated by running water.
      Consequently, responses of type II fibres to a vibrating sphere were not masked
      under flow conditions.

PMID- 12209341
TI  - Long-term light adaptation in photoreceptors of the housefly, Musca domestica.
AB  - The photoreceptors of many animals adapt, when illuminated, by reducing their
      sensitivities to light and improving their response speeds. Light adaptation is
      usually considered to be rapid and complete within minutes. However, under bright
      light conditions, I show that functionally significant improvements in impulse
      response amplitude and speed continue over the course of an hour in
      photoreceptors of the fly, Musca domestica. After sustained illumination, the
      average information rate, a measure of signalling performance, improved by 28% in
      a sample of sixteen photoreceptors. This long-term light adaptation is a robust
      phenomenon across animals and is repeatable within the same cell when light
      adapting sessions are separated by a period of darkness. White-noise analysis of
      voltage responses to light and current stimuli indicate that much of the long
      term changes observed are attributable to an improvement in the reliability with
      which photoreceptors register the timing of photon absorptions. It is also found
      that the impedance amplitude of the photoreceptor increases during long-term
      adaptation, suggesting that the area of the photoreceptor's membrane is reduced.

PMID- 12209342
TI  - Physiology and morphology of visual movement detector neurons in a crab
      (Decapoda: Brachyura).
AB  - Although visually elicited behaviors have been extensively studied in crabs,
      their investigation at the neurophysiological level is scant. The present study
      is a physiological and morphological description of intracellularly recorded and
      dye injected visual movement detector neurons that respond to the same stimulus
      that elicits the escape response in the crab Chasmagnathus granulatus. The
      neurons were investigated in intact animals. The response of movement detector
      neurons to the danger stimulus (an object moving above the animal) consists of a
      strong discharge of action potentials frequently superimposed on noisy graded
      potentials, whereas the response to stationary changes in illumination is weak or
      undetectable. The response to the moving stimulus is relatively independent of
      the background intensity and of the contrast between target and background.
      Repeated presentations of the moving stimulus produce rapid habituation of the
      neural response. Some of the neurons also respond to mechanical stimulation.
      These physiological results coincide with those from early studies on visual
      movement detector fibers of crustaceans achieved by extracellular recordings.
      However, there are no previous morphological studies of these neurons.
      Intracellular injection with Lucifer Yellow revealed that these neurons in
      Chasmagnathus arborize extensively in the internal medulla and in the lateral
      protocerebrum. They have their somata located in the cell body cluster laying
      beneath the internal medulla. Their axons project centripetally across the
      protocerebral tract.

PMID- 12209343
TI  - The sensory basis of olfactory search behavior in banded kokopu ( Galaxias
      fasciatus).
AB  - The sensory basis of olfactory search behavior was investigated in the banded
      kokopu, Galaxias fasciatus, using a flow tank. In the presence of a 2 cm s(-1)
      current flow, banded kokopu use both water current and chemical information to
      locate a food odor source. The superficial neuromasts of the lateral line system
      mediate the rheotactic component of the odor search. A physical block of one
      olfactory nostril did not affect the olfactory search strategy employed by banded
      kokopu in still water or in the presence of a current flow. Thus, there is no
      evidence that banded kokopu perform a bilateral comparison of the olfactory
      stimulus during their odor search. Previously, olfaction and gustation have been
      the only sensory systems shown to directly mediate orientation and movement
      towards odor sources in fish. The use of hydrodynamic cues by fish in location of
      an olfactory source has been previously proposed, but without direct experimental
      identification of the sensory systems employed. This study identifies the
      contributing roles of both olfactory and hydrodynamic sensory systems to the
      olfactory search repertoire of fish.

PMID- 12209344
TI  - Conduction velocity compensation for afferent fiber length in the trunk lateral
      line of the trout.
AB  - The trout lateral line contains about 122 trunk scales and is tens of centimeters
      long. The difference in time of arrival in the hindbrain of simultaneously
      elicited afferent responses from the neuromasts is unknown. Propagation times of
      single-fiber afferent responses to water motion revealed that their mean
      conduction velocity was lowest (13 m s(-1)) for fibers innervating a neuromast
      close to the operculum and highest (33 m s(-1)) for those close to the tail.
      Histological examination showed that the nerve close to the operculum comprises
      about 500 afferents and that this number diminishes from operculum to tail with
      4/scale. The mean diameter of the fibers changed from 12.5 micro m at the
      operculum to 7.5 micro m at three-quarters of the operculum-to-tail distance.
      Comparison of the distributions of diameters indicated that the fibers are
      tapered with the thick end towards the operculum. A model was developed
      describing the relationship between tapering and local conduction velocity. We
      conclude that simultaneous stimulation of all trunk neuromasts causes an average
      time-of-arrival difference in the hindbrain of 2.8 ms, which is 2.1 times less
      than the difference expected with a distance-independent conduction velocity.
      This suggests that tapering and velocity compensation are relevant for central
      processing of lateral line information.

PMID- 12209345
TI  - Temporal modulation transfer functions in auditory receptor fibres of the locust
      ( Locusta migratoria L.).
AB  - The temporal resolution of auditory receptors of locusts was investigated by
      applying noise stimuli with sinusoidal amplitude modulations and by computing
      temporal modulation transfer functions. These transfer functions showed mostly
      bandpass characteristics, which are rarely found in other species at the level of
      receptors. From the upper cut-off frequencies of the modulation transfer
      functions the minimum integration times were calculated. Minimum integration
      times showed no significant correlation to the receptor spike rates but depended
      strongly on the body temperature. At 20 degrees C the average minimum integration
      time was 1.7 ms, dropping to 0.95 ms at 30 degrees C. The values found in this
      study correspond well to the range of minimum integration times found in birds
      and mammals. Gap detection is another standard paradigm to investigate temporal
      resolution. In locusts and other grasshoppers application of this paradigm
      yielded values of the minimum detectable gap widths that are approximately twice
      as large than the minimum integration times reported here.

PMID- 12209346
TI  - Dendritic cell recovery after autologous stem cell transplantation.
AB  - There is persistent immunosuppression not only in allogeneic but also in
      autologous stem cell transplantation because humoral and cellular immunity may
      take a year or more to return to normal, with increased risk of infectious
      complications. This immune defect may also involve antigen presentation, in
      particular dendritic cell (DC) function. We evaluated DC subset reconstitution in
      58 patients who underwent bone marrow (BM) or peripheral blood (PB) autologous
      haematopoietic stem cell transplantation (HSCT). In all patients DC type 1 (DC1)
      and DC type 2 (DC2) were already significantly lower than in normal individuals
      before conditioning therapy (DC1/microl 3.1 +/- 1.0, DC2/microl 3.0 +/- 1.1). On
      day 0 and day +7 the mean DC1 and DC2 numbers were very low in both groups.
      Patients who received unmanipulated marrow or peripheral blood stem cells reached
      pre-conditioning levels of DC1 and DC2 cells on day +20. In patients receiving
      selected CD34 cells, DC increased slowly and pre-transplant counts were observed
      only on day +60. Nearly 'normal' levels of DC1 and DC2 could be observed in the
      first group from day +180, and were maintained thereafter; in CD34(+) selected
      patients DC1 and DC2 counts remained lower than normal. Our data emphasise that
      circulating antigen presenting cells (APC) recover quickly. It remains to be
      determined if DC frequency in PB reflects their tissue function. The relatively
      low incidence of infections in patients undergoing autologous transplantation,
      despite defective lymphocyte reconstitution, could be related to functionally
      efficient DC.

PMID- 12209348
TI  - Cyclophosphamide, etoposide and G-CSF to mobilize peripheral blood stem cells for
      autologous stem cell transplantation in patients with lymphoma.
AB  - We aimed to assess the effectiveness of cyclophosphamide, etoposide and G-CSF
      (C+E) to mobilize peripheral blood stem cells for autologous stem cell
      transplantation in patients with lymphoma. A matched cohort study was performed
      comparing patients mobilized with C+E to patients mobilized with cyclophosphamide
      and G-CSF (C alone). Patients were matched for disease, prior radiotherapy and a
      chemotherapy score reflecting the amount and type of prior chemotherapy. Thirty
      eight consecutive patients mobilized with C+E were compared with 38 matched
      controls. C+E was equivalent to C alone in terms of numbers of patients achieving
      a minimum threshold of > or =2 x 10(6)/kg CD34(+)cells (82% vs 79%, P = 0.74).
      C+E was superior, however, in terms of total CD34(+) yield (6.35 vs 3.3 x
      10(6)/kg, P < 0.01), achieving a target graft of > or =5 x 10(6)/kg (55% vs 34%,
      P = 0.04) and obtaining both a minimum (61% vs 32%, P < 0.01) and target (45% vs
      13%, P < 0.01) graft in one apheresis. This superiority was largely confined to
      patients with lower chemotherapy scores. There was no difference in neutrophil
      and platelet recovery or transfusion requirements for those who subsequently
      received high-dose therapy and stem cell transplantation. Thus, C+E improves the
      efficiency of peripheral blood stem cell collection, but does not increase the
      number of patients who can proceed to transplantation. Most of the benefit of the
      regimen was confined to patients who had not received extensive prior therapy.
      Novel strategies are required to increase the collection efficiency of 'hard to
      mobilize' patients.

PMID- 12209347
TI  - High stem cell dose will not compensate for T cell depletion in allogeneic non
      myeloablative stem cell transplantation.
AB  - The best strategies for non-myeloablative stem cell transplants (NST) are not
      known. We hypothesized that a high stem cell dose and post-transplant donor
      lymphocyte infusions (DLI) in a T cell-depleted NST setting may result in stable
      engraftment without severe GvHD. We used conditioning with 200 mg/kg
      cyclophosphamide, and ATG, a high peripheral stem cell dose of >10 x 10(6)
      CD34(+) cells/kg, T cell-depleted to <1 x 10(5) CD3(+) cells/kg followed by
      incremental DLI. Ten patients, 53 (42-61) years of age with hematological
      malignancy (CML in 3, MDS in 2, myeloma in 3 and CLL in 2) were included. All
      patients achieved initial engraftment, at a median 13.5 (10-20) days. Three
      patients achieved complete chimerism, four achieved a complete hematologic
      remission. In seven patients the graft ultimately failed. Acute GvHD grade II was
      seen in three patients after DLI. At a median follow-up of 28 months (range 15
      35), eight patients are alive, none died of treatment-related complications. NST
      with T cell depletion to prevent GVHD results in a high graft failure rate. High
      stem cell dose (> or =10 x 10(6) CD34(+)cells/kg) and post-transplant DLI will
      not compensate for the lack of T cells to ensure stable engraftment.

PMID- 12209349
TI  - Toxic megacolon: a life-threatening complication of high-dose therapy and
      autologous stem cell transplantation among patients with AL amyloidosis.
AB  - AL amyloidosis is a plasma cell disorder in which tissue deposition of
      immunoglobulin light chains leads to organ dysfunction. Recent reports of high
      dose therapy with autologous stem cell transplantation for amyloidosis suggest
      higher response rates and extended survival compared to those seen with
      conventional chemotherapy. However, substantial treatment-related toxicity has
      been observed. This case series describes our institutional experience with
      autologous transplantation in four patients with amyloidosis with an emphasis on
      unique gastrointestinal toxicities, including toxic megacolon.

PMID- 12209350
TI  - Mycophenolate mofetil for the treatment of acute and chronic GVHD is effective
      and well tolerated but induces a high risk of infectious complications: a series
      of 21 BM or PBSC transplant patients.
AB  - The use of mycophenolate mofetil (MMF) for prophylaxis of aGVHD and/or for
      treatment of acute or chronic GVHD is increasing. However, the benefit of MMF as
      an alternative to commonly used immunosuppressive agents still needs to be
      assessed. We ran a retrospective study on 21 consecutive patients (median age, 36
      years; range, 20-63) with aGVHD or extensive cGVHD following related (17) or
      unrelated (4) matched donor SCT (BM, 16; PBSC, 5) who received MMF (2 g/day)
      because of intolerance to or failure of CsA-containing combinations. Four of the
      six patients with aGVHD responded, and the response rate was 69% in cGVHD
      patients. We observed neither significant differences in terms of response rate
      for skin, liver and bowel nor dissociated response in cases of multiple organ
      involvement (67% of the patients). Response was the same for lichenoid and
      sclerodermatous skin cGVHD subtypes. No adverse effects, except diarrhea (three
      patients), were observed. However, 22 opportunistic or serious viral or bacterial
      infections occurred in 10 patients. Analysis of trough plasma levels showed a
      trend for a higher mean MPA concentration in patients responding to MMF. Our
      study highlights the high risk of infectious complications induced by the
      administration of MMF, an otherwise efficient and well-tolerated treatment for
      GVHD.

PMID- 12209351
TI  - Intensive chemotherapy for children and young adults with metastatic primitive
      neuroectodermal tumors of the soft tissue.
AB  - The MMT4 study was designed to explore an intensive chemotherapy regimen (MMT4
      89) and the role of high-dose melphalan (MMT4-91) in children with metastatic
      soft tissue sarcoma, including extraosseous peripheral neuroectodermal tumor
      (PNET). Thirty-one patients with PNET were treated between 1989 and 1995 (11
      according to MMT4-89 and 20 according to MMT4-91). Chemotherapy consisted of four
      CEVAIE cycles, each including three 3-week courses: CEV (carboplatin 500 mg/m(2),
      epirubicin 150 mg/m(2), vincristine 1.5 mg/m(2)), IVA ifosfamide 9 g/m(2),
      actinomycin 1.5 mg/m(2), vincristine 1.5 mg/m(2)), IVE (ifosfamide 9 g/m(2),
      etoposide 600 mg/m(2), vincristine 1.5 mg/m(2)). In MMT4-91 the fourth CEVAIE was
      replaced with melphalan 200 mg/m(2) with stem cell rescue. The CEV combination
      was evaluated as a window study. Surgery followed the second cycle. Radiotherapy
      was administered to post-surgical residual disease. The response rate was 55%
      after CEV, rising to 80% after the first CEVAIE. Twenty-five patients achieved
      complete remission (CR). Overall, the 5-year EFS was 22.6%: 36.4% and 15% for
      patients treated according to MMT4-89 and MMT4-91, respectively (P = 0.3). Local
      control was achieved in 77% of irradiated patients vs 45% of non-irradiated. Age
      >10 years was associated with significantly poorer outcome (P = 0.04). In
      conclusion, despite the high CR rate, intensive chemotherapy with or without high
      dose melphalan appeared to have little impact on the survival of patients with
      metastatic extraosseus PNET.

PMID- 12209352
TI  - Early infections in adults undergoing matched related and matched
      unrelated/mismatched donor stem cell transplantation: a comparison of incidence.
AB  - We compared the incidence of early infectious complications between matched
      related (MR) and matched unrelated/mismatched (MU/MM) allogeneic stem cell
      transplant (allo-SCT) recipients in a single centre over a 6-year period in 214
      consecutive adult patients. Early infections were defined as occurring from
      hospital admission for SCT until discharge. One hundred and fifty-nine patients
      received an allograft from MR donors and 55 patients received MU/MM allo-SCT. One
      hundred and eight of 214 patients had 147 episodes of fever. Ninety-three
      episodes (63%) were due to clinically or microbiologically documented infections
      and 54 episodes (37%) to fever not related to infection. Patients undergoing
      MU/MM transplantation tended to have more documented infections compared to
      recipients of MR allo-SCT (P = 0.06). Significantly more MU/MM transplant
      recipients had breakthrough infections with Herpes simplex virus type 1 (HSV-1, P
      = 0.003), and more CMV reactivation (P = 0.015). The mortality rate in all
      patients during hospitalisation post-SCT was 6.3% in MR and 18.2% in MU/MM allo
      SCT recipients (P = 0.009). Early mortality was associated with infection in 70%
      of the patients, with a similar distribution between MR and MU/MM transplant
      recipients. However, MU/MM transplant recipients had significantly more early
      deaths due to toxic causes (P < 0.001). We conclude that early post-transplant
      MU/MM transplant recipients tend to have more documented infections, and have
      significantly more breakthrough infections with HSV-1 and more CMV reactivation.
      MU/MM transplant recipients are at higher risk of early mortality, especially due
      to toxic causes.

PMID- 12209353
TI  - The efficacy of prophylactic outpatient antibiotics for the prevention of
      neutropenic fever associated with high-dose etoposide (VP-16) for stem cell
      mobilization.
AB  - High-dose etoposide (2 g/m(2)) plus G-CSF is a very effective regimen for
      peripheral blood progenitor cell (PBPC) mobilization. Unfortunately, neutropenia
      is common. The infectious complications associated with high-dose etoposide have
      not been previously described. After noting a high incidence of hospitalizations
      for neutropenic fever, we began a vigorous prophylactic antibiotic regimen for
      patients receiving high-dose etoposide plus G-CSF, attempting to reduce
      infectious complications. Ninety-eight patients underwent etoposide mobilization
      between December 1997 and June 2000. Three chronological patient groups received:
      (1) no specific antibiotic prophylaxis (n = 44); (2) vancomycin i.v., cefepime
      i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27); and (3) vancomycin
      i.v., clarithromycin p.o., and ciprofloxacin p.o. (n = 27). The patients not
      receiving antibiotic prophylaxis had a 68% incidence of hospitalization for
      neutropenic fever. In the patients receiving prophylaxis, the incidence was
      reduced to 26% and 15% respectively, for an overall incidence of 20% (P < 0.001
      for comparison between prophylaxed and unprophylaxed groups). We conclude that
      etoposide mobilization is associated with a significant incidence of neutropenic
      fever, which can be substantially reduced by a vigorous antimicrobial
      prophylactic program.

PMID- 12209354
TI  - Monitoring cytomegalovirus infection by antigenemia assay and two distinct plasma
      real-time PCR methods after hematopoietic stem cell transplantation.
AB  - We compared a CMV virus load determined by real-time PCR with an antigenemia
      value to analyze the correlation between these two methods. We also compared the
      values for virus load determined by the two distinct real-time PCR methods, which
      amplify the US17 region and immediate-early (IE) gene of CMV, respectively, to
      evaluate the reliability of these methods. Two hundred and sixty-five samples
      were obtained weekly from 29 patients, who had engraftment after unrelated bone
      marrow transplantation or HLA-mismatched related blood stem cell transplantation.
      CMV infection was detected in 115 samples from 22 patients by US17-PCR and 69
      samples from 20 patients by the antigenemia assay. Fifty-eight samples were
      positive for both assays, but 57 and 11 samples were positive only for US17-PCR
      and antigenemia, respectively. A good correlation of the results of US17-PCR and
      antigenemia was demonstrated (r = 0.61). All antigenemia-positive samples and
      randomly selected antigenemia-negative samples were subjected to IE-PCR. The
      results of IE-PCR showed a good correlation with those of antigenemia (r = 0.64).
      Furthermore, the best correlation was observed between US17-PCR and IE-PCR (r =
      0.83). In conclusion, both real-time PCR methods showed a good correlation with
      the antigenemia assay, and could be used to monitor CMV infection after
      hematopoietic stem cell transplantation.

PMID- 12209355
TI  - Successful treatment of post-transplant lymphoproliferative disorder in
      autologous blood stem cell transplant recipients.
AB  - We report three cases of post-transplant lymphoproliferative disorder (PTLD) in
      the context of autologous stem cell transplantation (ASCT) for multiple myeloma
      (MM) and non-Hodgkin's lymphoma. The first two cases received ASCT for MM, one
      with a CD34-selected autograft and the other with an unmanipulated autograft.
      Both these cases of PTLD achieved a complete response following treatment with
      IVIG, gancyclovir, solumedrol and interferon (IFN). The third case received ASCT
      with an unmanipulated autograft for relapsed angioimmunoblastic lymphoma. He also
      achieved a complete response but only after rituximab was added to IVIG,
      gancyclovir, solumedrol and IFN. None of these patients experienced a relapse of
      their PTLD with follow-up ranging from 1.5 to 5 years. These cases highlight the
      importance of considering PTLD in the differential diagnosis of lymphadenopathy
      and fever post ASCT. They also demonstrate the possibility of durable complete
      remission of post-ASCT PTLD following antiviral and immune modulating therapy.

PMID- 12209356
TI  - Combination treatment of bullous pemphigoid with anti-CD20 and anti-CD25
      antibodies in a patient with chronic graft-versus-host disease.
AB  - In this case report we describe a novel treatment with two chimeric monoclonal
      antibodies (MoAb) targeting the autoimmune B cell clone responsible for bullous
      pemphigoid (BP) as a manifestation of steroid refractory chronic graft-versus
      host disease (GVHD) that developed after unrelated cord blood transplantation.
      Monitoring the BP-specific circulating antibodies and CD25-expressing activated T
      lymphocyte subset led us to combine anti-CD20 (Rituximab) mediated B cell
      ablation with anti-CD25 (Daclizumab) therapy to block CD4(+) T cell help.
      Complete clinical and serologic response was achieved within 4 weeks of
      initiation of therapy allowing global immunosuppression to be dramatically
      reduced.

PMID- 12209357
TI  - Toxic epidermal necrolysis: differential diagnosis of an epidermolytic dermopathy
      in a hematopoietic stem cell transplant recipient.
AB  - Toxic epidermal necrolysis (TEN) is an epidermolytic skin disorder associated
      with drug administration. It is associated with an erythematous rash with full
      thickness epidermal loss and characteristic histology. A 35-year-old woman
      underwent allogeneic hematopoietic stem cell transplantation (HSCT) for severe
      aplastic anemia (SAA). She developed an acute epidermolytic rash and TEN was
      diagnosed on the basis of skin biopsy. In the HSCT setting, TEN should be thought
      of as an important differential diagnosis of epidermolytic dermopathies. The most
      distinctive diagnostic test in the differential diagnosis of these disorders is
      skin biopsy

PMID- 12209358
TI  - Cytokine gene polymorphism in human disease: on-line databases, supplement 2.

PMID- 12209359
TI  - Genetic variability in response to infection: malaria and after.
AB  - Recent studies have shown that the relatively short period of exposure of human
      populations to malaria has left in its wake a wide range of genetic diversity.
      And there is growing evidence that other infectious agents have, or are, having
      the same effect. By integrating further studies of human populations with genetic
      analyses of susceptibility to murine malaria it should now be possible to
      determine some of the mechanisms involved in the variation of susceptibility to
      infectious disease, information which may have important practical implications
      for both the diagnosis and better management of these conditions.

PMID- 12209360
TI  - Evidence for a locus (IDDM16) in the immunoglobulin heavy chain region on
      chromosome 14q32.3 producing susceptibility to type 1 diabetes.
AB  - Type 1 diabetes results from autoimmune destruction of pancreatic islet beta
      cells, possibly initiated or exacerbated by viral infections. Recent studies have
      demonstrated that antibodies towards enterovirus and autoantibodies towards islet
      cell components develop in the long preclinical phase of type 1 diabetes. We
      therefore hypothesised that susceptibility to type 1 diabetes could be influenced
      by genetic factors controlling production of antiviral antibodies or
      autoantibodies or both. To search for evidence of linkage or association (linkage
      disequilibrium) between type 1 diabetes and the immunoglobulin heavy chain (IGH)
      region, 351 North American and British families with > or =2 diabetic children
      were genotyped for IGH region microsatellites. Using affected sibpair analysis,
      significant evidence for linkage was obtained for three markers close to the IGH
      gene cluster (P values 0.004, 0.002, 0.002). No evidence was found for
      association using family-based methods. To attempt to confirm these findings, a
      smaller dataset (241 families, 138 with > or =2 diabetic children) from Denmark,
      a more genetically-homogeneous population, was genotyped for one marker only.
      These families showed no linkage, but significant evidence for association (P =
      0.019). This study suggests that a locus (assigned the symbol IDDM16) in the IGH
      region, possibly an IGH gene, influences susceptibility to type 1 diabetes.

PMID- 12209361
TI  - A genotypic association implicates myeloperoxidase in the progression of hepatic
      fibrosis in chronic hepatitis C virus infection.
AB  - The hepatitis C virus (HCV) is a major cause of liver disease and the
      complications of cirrhosis. Liver biopsies, performed prior to the development of
      liver cirrhosis, characteristically show an inflammatory cell infiltrate with
      varying degrees of fibrosis. Precisely how HCV infection induces hepatic
      fibrogenesis is unknown. Recent studies suggest the release of oxidants,
      cytokines and proteases from the host immune system are key to the development of
      fibrosis. Macrophages and neutrophils, cells heavily represented in the
      inflammatory cell response, contain the oxidant generating enzyme myeloperoxidase
      (MPO). Cellular levels of MPO can be influenced by a functional promotor
      polymorphism, -463G/A, which precedes the MPO gene. We examined the relationship
      between this MPO promotor genotype and the degree of fibrosis in 166 patients
      with chronic HCV infection. All patients had previously participated in clinical
      drug trials for the treatment of chronic HCV infection. The MPO genotype was
      determined from cryo-preserved lymphocytes obtained from patients prior to
      treatment. The degree of fibrosis was estimated from liver biopsy specimens
      obtained prior to treatment. We found that patients with the MPO GA/AA genotype
      were more likely to have advanced fibrosis scores compared with those with the GG
      genotype: Of the patients with GG genotype, 78% (79 of 102 cases) had lower
      Knodell Fibrosis scores of 0 or 1, compared to 56% (37 of 64 cases) of patients
      with GA/AA genotype (P < 0.05). The mechanism(s) by which MPO contributes to
      fibrosis progression remains to be determined.

PMID- 12209362
TI  - Genetic analysis of multicase families of visceral leishmaniasis in northeastern
      Brazil: no major role for class II or class III regions of HLA.
AB  - Familial aggregation, high relative risk to siblings, and segregation analysis,
      suggest genetic control of visceral leishmaniasis in Brazil. Class II gene
      effects in mice, and high circulating tumour necrosis factor alpha in humans,
      provide reasons to target HLA. Fifteen polymorphic markers across 1.03 Mb (DQB1
      to TNFa) were genotyped (87 multicase families; 638 individuals). Model-based
      parametric analyses using single-point combined segregation and linkage in COMDS,
      or multi-point linkage in ALLEGRO, failed to detect linkage. Model-free
      nonparametric affected sibling pair (SPLINK) or NPL(all) score (ALLEGRO) analyses
      also failed to detect linkage. Information content mapping confirmed sufficient
      marker information to detect linkage. Analysis of simulated data sets
      demonstrated that these families had 100% power to detect NPL(all) scores of 5 to
      6 (>LOD4; P < 0.00001) over the range (7% to 61%) of age-related penetrances for
      a disease susceptibility gene. The extended transmission disequilibrium test
      (TDT) showed no consistent allelic associations between disease and the 15 loci.
      TDT also failed to detect significant associations between extended haplotypes
      and disease, consistent with failure to detect significant linkage disequilibrium
      across the region. Linkage disequilibrium between adjacent groups of markers
      (HLADQ/DR; 82-1/82-3/-238bpTNFA; LTA/62/TNFa) was not accompanied by significant
      global haplotype TDT associations with disease. The data suggest that class
      II/III regions of HLA do not contain major disease gene(s) for visceral
      leishmaniasis in Brazil.

PMID- 12209363
TI  - Association of low-density lipoprotein receptor polymorphisms and outcome of
      hepatitis C infection.
AB  - The low-density lipoprotein receptor (LDLR) has been proposed to promote
      hepatitis C virus endocytosis and the cell membrane protein CD81 may also promote
      HCV host cell entry. The CD81 gene was sequenced to screen for novel
      polymorphisms, but no SNPs were identified. Polymorphisms within the LDLR gene
      are associated with the pathogenesis of familial hypercholesterolemia,
      atherosclerosis and obesity. We therefore studied genetic variation within the
      LDLR gene and clinical features of hepatitis C infection. An amino acid change in
      exon 8 was associated with severity of fibrosis; a SNP in exon 10 correlated with
      viral clearance and overall inflammation, and a SNP in the 3'UTR appeared to
      influence treatment response. There were no other significant associations
      between any of the SNPs studied and the clinical measures of hepatitis C
      infection. We furthermore report on linkage disequilibrium within the gene and
      haplotype frequencies in our population. Our findings support a possible role for
      the LDLR in the modulation of disease progression by affecting immune responses,
      rather than functioning as receptor for HCV.

PMID- 12209364
TI  - A weak association of HLA-B*2702 with Behcet's disease.
AB  - This study aimed to analyse the association of HLA-B alleles other than -B51 with
      Behcet's disease (BD). We also investigated the frequency of HLA-B alleles
      sharing the same natural killer cell immunoglobulin-like receptor (KIR) binding
      sequence with HLA-B51. Broad-genotyping of HLA-B locus by PCR-SSOP in 174 Turkish
      BD patients and 191 healthy controls confirmed the strong association of B*51
      with BD (60.9% in BD patients, 24.6% in healthy controls, OR = 4.78). No other
      HLA-B allele was identified showing an association with BD after adjusting for
      multiple testing or by using relative predispositional effects (RPE) analysis
      after the deletion of B*51. HLA-B alleles reacting with the sequence specific
      oligonucleotide probe 23, which corresponds to the KIR binding site of B*51, were
      found to be positive in 127 BD patients (73%) and 90 controls (47%) (OR = 3.03,
      95% CI 2-4.7). The repeated RPE analysis after separating HLA-B alleles carrying
      B51-KIR binding sequence as distinct alleles within a broad-type allele group
      revealed B*2702 allele as the only allele showing an association with BD after
      the deletion of B*51. Selective increase of B*2702, the only B*27 allele carrying
      the same KIR binding sequence with B*51, warrants investigation of the
      possibility of interaction of HLA molecules with KIRs on NK or other T cells in
      the pathogenesis of BD.

PMID- 12209365
TI  - LMP2 and LMP7 gene polymorphism in Mexican populations: Mestizos and Amerindians.
AB  - Low molecular weight polypeptide (LMP) genes are located within the major
      histocompatibility complex and have been associated with autoimmune diseases such
      as ankylosing spondylitis. In order to define the distribution of LMP genes in
      Mexican populations, the LMP2 and LMP7 polymorphism was analyzed in 312 Mexican
      individuals (95 Mexican Mestizos, 48 Nahuas, 56 Mazatecans, 50 Teenek, and 63
      Mayos) belonging to different ethnic groups. In Mexican populations both Mestizos
      and Amerindians presented similar distribution of LMP2 and LMP7 polymorphisms,
      except Nahuas and Mayos who presented the higher frequencies of LMP2-H/H and the
      lowest frequencies of LMP2-H/R genotypes (P < 0.05 when compared with Mexican
      Mestizos). The LMP7-K/K genotype was absent in Nahuas, Teenek and Mayos and only
      one Mazatecan individual presented this genotype. Differences with other
      populations were found in Mexicans. An increased frequency of LMP2-H and a
      decreased frequency of LMP2-R alleles were observed in Mexican Amerindians
      (Nahuas and Mayos) when compared with Brazilian Amerindians (Kaingang and
      Guarani) and Caucasians (Spaniards) (P < 0.05). All Mexican populations (Mestizos
      and Amerindians) presented an increased frequency of LMP7-Q allele and a
      decreased frequency of LMP7-K allele when compared to Brazilian Amerindians
      (Kaingang), Caucasians (United States) and Asian (Japan) populations (P < 0.05).
      Genetic distances showed that Mexican Mestizos have an important relation with
      Spaniards and with all Mexican Amerindians. The present data corroborate the
      influence of Spaniard and Amerindian genes in the Mexican Mestizo population and
      could help to define the true significance of LMP polymorphism as genetic and
      evolutive marker in the Amerindian populations.

PMID- 12209367
TI  - Rank nonsense?

PMID- 12209366
TI  - Tunisian endemic pemphigus foliaceus is associated with desmoglein 1 gene
      polymorphism.
AB  - Desmoglein 1 is the target antigen and probably the initiating immunogen of the
      autoantibody response in pemphigus foliaceus (PF), a blistering autoimmune skin
      disease. We previously showed that the desmoglein 1 gene (DSG1) is polymorphic
      and that one of its variants is associated with the sporadic form of PF observed
      in France. Herewith, we report, based on a case-control analysis, that the same
      DSG1 polymorphism participates in susceptibility to the endemic form of PF seen
      in Tunisia and, thus, show that common genetic factors govern the breakage of
      tolerance to desmoglein 1 in different epidemiological and environmental
      situations.

PMID- 12209368
TI  - The high-fat Greek diet: a recipe for all?
AB  - OBJECTIVE: To examine critically the published results of dietary surveys on the
      fat content of the Greek diet, and to assess its evolution and its relationship
      to the health of the Greeks. To consider the implications of these findings for
      current views on the nature and health implications of the traditional
      Mediterranean diet and how best to define it for use in modern policy making.
      DESIGN: A systematic review of the literature on food consumption in Greece.
      SETTING: Greece. RESULTS: The first fully published data on the fat content of
      the Greek diet-the Seven Countries Survey-relates only to a small number of adult
      males in Crete and Corfu; the legitimacy of extrapolating these results to the
      rest of Greece is questioned. Earlier studies and chemical validation of intakes
      point to a lower fat content of the traditional diet than that inferred for
      Crete. Nearly all later surveys relate only to urban groups in Athens (mostly
      case-control hospital-based samples) and a variety of non-representative Cretan
      groups. Only two studies are larger and more representative, but one uses FAO
      food balance-sheets to reflect the national diet, and the other surveyed school
      age children in three out of the 52 Greek counties. Unfortunately recent dietary
      studies have proved unreliable, given the continuing lack of national food
      composition tables with survey methods which proved inaccurate for dietary fat
      content. A progressive upward trend in total and saturated fat intake appears to
      have occurred with all health indicators in relation to fat indicating remarkable
      increases in adult and childhood obesity with attendant progressive deterioration
      in cardiovascular mortality and its risk factors, ie hypertension and diabetes.
      These data emphasise the need to alter current nutritional advice in Greece,
      particularly when it focuses on the promotion of olive oil and a high-fat diet.
      CONCLUSIONS: The findings reaffirm low-moderate fat policies for optimum health,
      within which olive oil can be an important component of the diet.

PMID- 12209369
TI  - Evaluation of nutritional assessment techniques in elderly people newly admitted
      to municipal care.
AB  - OBJECTIVES: To evaluate the Subjective Global Assessment (SGA) and the Mini
      Nutritional Assessment (MNA) with regard to validity using a combination of
      anthropometric and serum-protein measurements as standard criteria to assess
      protein-energy malnutrition (PEM). DESIGN: Cross-sectional study with consecutive
      selection of residents aged >or=65 y. SETTING: A municipality in the south of
      Sweden. SUBJECTS: During a year, starting in October 1996, 148 females and 113
      males, aged >or=65-104 y of age, newly admitted to special types of housing for
      the elderly, were included in the study. RESULTS: According to SGA, 53% were
      assessed as malnourished or moderately malnourished on admission. The
      corresponding figure from MNA was 79% malnourished or at risk of malnutrition.
      Both tools indicated that anthropometric values and serum proteins were
      significantly lower in residents classified as being malnourished (P<0.05).
      Sensitivity in detecting PEM was in SGA 0.93 and in MNA 0.96 and specificity was
      0.61 and 0.26, respectively. Using regression analysis, weight index and serum
      albumin were the best objective nutritional parameters in predicting the SGA- and
      MNA classifications. Item 'muscle wasting' in SGA and 'self-experienced health
      status' in MNA showed most predictive power concerning the odds of being assessed
      as malnourished. CONCLUSIONS: SGA was shown to be the more useful tool in
      detecting residents with established malnutrition and MNA in detecting residents
      who need preventive nutritional measures.

PMID- 12209370
TI  - Daily energy expenditure, activity patterns, and energy costs of the various
      activities in French 12-16-y-old adolescents in free living conditions.
AB  - BACKGROUND: Changes in lifestyle and increases in sedentary activities during
      recent decades have been shown to contribute to the prevalence of overweight in
      adolescents. OBJECTIVES: To determine the inter-individual variability and the
      day-to-day variations in daily energy expenditure (DEE) and activity pattern, and
      the energy costs and EE of the various activities of adolescents in free-living
      conditions. DESIGN: Sixty adolescents (four groups of 14-16 boys or girls aged 12
      16 y) participated in this cross-sectional study during spring or autumn.
      Activity patterns and EE were determined during five consecutive days, using both
      a diary and the heart rate recording method validated by whole-body calorimetry
      and laboratory tests. RESULTS: Mean DEE increased significantly with age in boys,
      but not in girls. However, the physical activity level did not vary significantly
      with sex and age. Mean DEE was significantly higher in spring than in autumn in
      the 12.6-y-old subjects. It was also 21% higher during the free days than during
      the schooldays in the active subjects, but 7% lower in the sedentary subjects.
      The energy cost of 22 activities was determined. Time and energy devoted to
      moderate and sport activities exhibited great inter-individual variability. They
      were lower in girls than in boys and decreased with age. The increase in EE
      resulting from moderate and sport activities instead of sedentary activities
      ranged from 0.2 to 2.7 MJ/day over the week. CONCLUSION: The great variability in
      DEE of adolescents resulted mainly from differences in the nature, duration and
      intensity of physical activities during the free days.

PMID- 12209371
TI  - Therapeutic effects of psyllium in type 2 diabetic patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of psyllium in type
      2 diabetic patients. DESIGN: The study included three phases: phase 1 (1 week),
      phase 2 (treatment, 14 g fibre/day, 6 weeks) and phase 3 (4 weeks). At the end of
      each phase a clinical evaluation was performed after the ingestion of a test
      breakfast of 1824.2 kJ (436 kcal). Measurements included concentrations of blood
      glucose, insulin, fructosamine, GHbA(1c), C-peptide and 24 h urinary glucose
      excretion. In addition, uric acid, cholesterol and several mineral and vitamin
      concentrations were also evaluated. SETTING: The study was performed at the
      Department of Pharmacology, Toxicology and Nursing at the University of Leon
      (Spain). SUBJECTS: Twenty type 2 diabetic patients (12 men and 8 women)
      participated in the study with a mean age of 67.4 y for men and 66 y for women.
      The mean body mass index of men was 28.2 kg/m(2) and that of women 25.9 kg/m(2).
      RESULTS: Glucose absorption decreased significantly in the presence of psyllium
      (12.2%); this reduction is not associated with an important change in insulin
      levels (5%). GHbA(1c), C-peptide and 24 h urinary glucose excretion decreased
      (3.8, 14.9 and 22.5%, respectively) during the treatment with fibre (no
      significant differences) as well as fructosamine (10.9%, significant
      differences). Psyllium also reduced total and LDL cholesterol (7.7 and 9.2%,
      respectively, significant differences), and uric acid (10%, significant
      difference). Minerals and vitamins did not show important changes, except sodium
      that increased significantly after psyllium administration. CONCLUSIONS: The
      results obtained indicate a beneficial therapeutic effect of psyllium (Plantaben)
      in the metabolic control of type 2 diabetics as well as in lowering the risk of
      coronary heart disease. We also conclude that consumption of this fibre does not
      adversely affect either mineral or vitamin A and E concentrations. Finally, for a
      greater effectiveness, psyllium treatment should be individually evaluated.

PMID- 12209372
TI  - Long-term consumption of fermented dairy products over 6 months increases HDL
      cholesterol.
AB  - OBJECTIVE: Assessment of the hypocholesterolaemic effect of yoghurt supplemented
      with Lactobacillus acidophilus 145 and Bifidobacterium longum 913 in women.
      DESIGN: The cross-over study consisted of three periods (7 weeks each): first
      period, control yoghurt for all 29 women; second period, probiotic yoghurt for 18
      women, control yoghurt for 11 women; third period, the reverse of that in the
      second period. SETTING: Department of Nutritional Physiology, Institute of
      Nutritional Science, Friedrich Schiller University, Jena. SUBJECTS: Twenty-nine
      healthy women, aged 19-56 y. Fifteen of these were normocholesterolaemic and 14
      women were hypercholesterolaemic. INTERVENTION: Yoghurt (300 g) daily containing
      3.5% fat and starter cultures of Streptococcus thermophilus and L. lactis.
      Probiotic yoghurt was the control yoghurt enriched with L. acidophilus 145, B.
      longum 913 and 1% oligofructose (synbiotic). RESULTS: The mean serum
      concentration of total cholesterol and the LDL cholesterol was not influenced by
      the synbiotic (P>0.05). The HDL concentration increased significantly by 0.3
      mmol/l (P=0.002). The ratio of LDL/HDL cholesterol decreased from 3.24 to 2.48
      (P=0.001). CONCLUSIONS: The long-term daily consumption of 300 g yoghurt over a
      period of 21 weeks (control and synbiotic) increased the serum concentration of
      HDL cholesterol and lead to the desired improvement of the LDL/HDL cholesterol
      ratio.

PMID- 12209373
TI  - Effect of riboflavin supplementation on plasma homocysteine in elderly people
      with low riboflavin status.
AB  - OBJECTIVE: To investigate the effect of riboflavin supplementation on plasma
      homocysteine (tHcy) concentrations in healthy elderly people with sub-optimal
      riboflavin status. DESIGN: A double-blind, randomized, placebo-controlled
      riboflavin supplementation trial. SETTING: Community based study in Northern
      Ireland. SUBJECTS: From a screening sample of 101 healthy elderly people, 52 had
      sub-optimal riboflavin status (erythrocyte glutathione reductase activation
      coefficient, EGRAC>or=1.20) and were invited to participate in the study.
      INTERVENTION: The intervention had two parts. Part 1 was a 12 week randomized
      double blind, placebo-controlled intervention with riboflavin (1.6 mg/day).
      Following completion of part 1, the placebo group went on to part 2 of the study
      which involved supplementation with folic acid (400 micro g/day) for 6 weeks
      followed by folic acid and riboflavin (1.6 mg/day) for a further 12 weeks, with a
      16 week washout period post-supplementation. The purpose of part 2 was: (a) to
      address the possibility that homocysteine-lowering in response to riboflavin may
      be obscured by a much greater effect of folate, and that, once folate status was
      optimized, a dependence of homocysteine on riboflavin might emerge; and (b) to
      demonstrate that these subjects had homocysteine concentrations which could be
      lowered by nutritional intervention. RESULTS: Although riboflavin supplementation
      significantly improved riboflavin status in both parts 1 and 2 of the study
      (P<0.001 for each), tHcy concentrations were unaffected (P=0.719). In contrast,
      folic acid supplementation (study part 2) resulted in a homocysteine lowering of
      19.6% (P=0.001). CONCLUSION: Despite the metabolic dependency of tHcy on
      riboflavin, it did not prove to be an effective homocysteine-lowering agent, even
      in the face of sub-optimal riboflavin status.

PMID- 12209374
TI  - Body composition in early onset eating disorders.
AB  - BACKGROUND: Body mass index (BMI) or equivalent weight for height indices are the
      most widely used measures of body composition in early onset and adolescent
      eating disorders. Although of value as screening instruments the limitation in
      disease states is their inability to discriminate fat and fat-free components of
      body weight. OBJECTIVE: To compare height-adjusted fat and fat-free components of
      body composition in children and young adolescents with different types of eating
      disorders with those of age matched reference children. DESIGN: Weight, height,
      triceps and subscapular skinfold thickness were measured in 172 children (aged 7
      16 y) with eating disorders receiving specialist treatment. Fat mass index (FMI)
      and fat-free mass index (FFMI) were calculated using Slaughter's and Deurenberg's
      equations and normalisation for height. Using data from 157 normal children,
      representative of the UK 1990 growth reference data, reference curves for FMI and
      FFMI+/-2 s.d. were derived. Results for patient groups were superimposed on these
      reference curves. RESULTS: FMI and FFMI were both reduced in eating disorders
      associated with malnutrition, including anorexia nervosa (AN). AN subjects did
      not differ from other subjects with comparable degrees of malnutrition. Children
      with eating disorders of normal weight, such as bulimia nervosa and selective
      eating, did not differ significantly from reference children in their relative FM
      and FFM. CONCLUSIONS: FM and FFM merit independent consideration in disorders of
      malnutrition in children, rather than expressing data as percentage body fat or
      percentage BMI. The implications of loss of FFM on growth and development merit
      further investigation.

PMID- 12209375
TI  - Self-perception of being overweight in Spanish adults.
AB  - OBJECTIVE: To describe the frequency, distribution and trend in misperceived
      overweight and obesity. DESIGN: Three independent cross-sectional studies carried
      out in 1987, 1995 and 1997 over representative samples of Spanish adult
      population. SETTING: Spanish adult population aged 20 y and over. SUBJECTS AND
      INTERVENTIONS: A total of 11 496 men and women aged 20 y and over with a body
      mass index (BMI) >or=25 kg/m(2). MAIN OUTCOME MEASURES: Prevalence and time trend
      of misperceived overweight and obesity based on self-perceived weight and height.
      RESULTS: Some 28.4% of the population did not perceive themselves to be
      overweight or obese in 1987 (26.9% in 1995/97). Overweight was more frequently
      misperceived among men, persons over 64 y of age, those residing in rural areas
      and those with an elementary educational level. The largest percentages of
      misperceived overweight were in the more moderate levels of BMI: 50% of men and
      30% of women with a BMI of 25-26.9 kg/m(2) in 1995/1997 did not perceive
      themselves to be overweight. CONCLUSIONS: Misperceived overweight and obesity is
      frequent in the adult population in Spain. Some social and cultural factors may
      explain its higher frequency in men, older individuals and those with elementary
      level of education. The fact that most of those who do not perceive themselves to
      be overweight are in the moderate levels of overweight should be taken into
      account when designing strategies for the prevention and control of overweight
      and obesity in the general population.

PMID- 12209376
TI  - Selenium status and associated factors in a British National Diet and Nutrition
      Survey: young people aged 4-18 y.
AB  - OBJECTIVE: Assessment of selenium status to provide normative reference values,
      and investigation of associated socio-demographic factors, in a national sample
      of British young people aged 4-18 y. SETTING: National Diet and Nutrition Survey
      a nationwide cross-sectional sample of young people aged 4-18 y living in
      mainland Britain in 1997. METHODS: Selenium status was measured, mainly in
      fasting blood samples, by plasma selenium concentration in 1127 participants, by
      red blood cell (RBC) selenium concentration in 1112, and by whole-blood
      glutathione peroxidase (GPx) activity in 658. RESULTS: No evidence of severe
      selenium deficiency or toxicity was observed. Plasma selenium concentration was
      directly correlated with RBC selenium concentration, and both were associated
      directly, although less strongly, with GPx activity. Plasma and RBC selenium
      concentrations increased significantly with age, with RBC concentrations
      significantly higher in older girls than boys. Region of domicile exhibited a
      significant relationship. Associations also occurred with parental occupational
      social class, selenium concentrations being higher in more socially advantaged
      children. Black and Indian children had considerably higher concentrations than
      Caucasian children. Concentrations, especially of plasma selenium, were
      significantly lower in children either (or both) of whose parents were smokers,
      although, unexpectedly, there was no evidence that children who themselves smoked
      had lower levels. CONCLUSIONS: The observed associations between selenium status
      indices and age, gender, social class, parental smoking and ethnic group indicate
      a complex network of biological factors which determine selenium concentrations
      in blood components, and which thus need to be controlled for when using these
      indices to assess selenium status in young people. SPONSORSHIP: The survey was
      commissioned jointly by the Department of Health and the Ministry of Agriculture,
      Fisheries and Food, whose responsibility has since been transferred to the Food
      Standards Agency. Support for the further analysis presented in this paper was
      provided by the Department of Health.

PMID- 12209377
TI  - Cross-sectional association between total level and type of alcohol consumption
      and glycosylated haemoglobin level: the EPIC-Norfolk Study.
AB  - OBJECTIVE: To investigate the association between total level and type of alcohol
      consumed and glycaemia. DESIGN: Cross-sectional study. SETTING: The EPIC-Norfolk
      Study, a population-based cohort study of diet and chronic disease. SUBJECTS AND
      METHODS: Non-diabetic men (n=2842) and women (n=3572), aged 40-78 y. Alcohol
      intake was assessed by self-reported questionnaire, and glycaemia measured by
      glycosylated haemoglobin (HbA(1c)). RESULTS: Ten percent of men and 18% of women
      reported drinking no alcohol. Among drinkers, median alcohol intake was 8
      units/week for men and 3 units/week for women. In analyses stratified by sex and
      adjusted for age, total energy intake, education, fruit and vegetable intake,
      smoking, family history of diabetes, physical activity, body mass index and
      waist:hip ratio, alcohol intake was inversely associated with HbA(1c) in men and
      women, although the association was stronger in women. A 1 unit/week increase in
      alcohol intake was associated with 0.0049% (s.e.=0.00223; P-value=0.028) and
      0.017% (s.e.=0.00343; P-value <0.001) reduction in HbA(1c) in men and women
      respectively. In similar multivariate analyses, wine intake was inversely
      associated with HbA(1c) in men, and wine, spirits and beer intake were inversely
      associated with HbA(1c) in women. When also adjusted for total alcohol intake,
      only the association between wine intake and HbA(1c) in men remained significant.
      CONCLUSION: Alcohol intake was associated with lower HbA(1c) level, an
      association not explained by confounding. The distinction between type of alcohol
      consumed was particularly important in men.

PMID- 12209378
TI  - Plasma concentrations of the flavonoids hesperetin, naringenin and quercetin in
      human subjects following their habitual diets, and diets high or low in fruit and
      vegetables.
AB  - OBJECTIVES: To determine the fasting plasma concentrations of quercetin,
      hesperetin and naringenin in human subjects consuming their habitual diets, and
      diets either high or low in fruit and vegetables. To investigate whether plasma
      concentrations of flavanones can serve as biomarkers of their intake. DESIGN:
      This was a cross-over, strictly controlled dietary intervention consisting of a 2
      week baseline period, and two 5 week dietary periods with a 3 week wash-out
      period in between. The low-vegetable diet contained few fruit and vegetables and
      no citrus fruit. The high-vegetable diet provided various fruits and vegetables
      daily including on average one glass of orange juice, one-half orange and one
      half mandarin. SUBJECTS: Thirty-seven healthy females. RESULTS: The high
      vegetable diet provided 132 mg of hesperetin and 29 mg of naringenin. The low
      vegetable diet contained no flavanones. The mean plasma hesperetin concentration
      increased from 12.2 nmol/l after the low-vegetable diet to 325 nmol/l after the
      high-vegetable diet. The respective increase for naringenin was from <73.5 nmol/l
      for all subjects to a mean value of 112.9 nmol/l. The mean plasma quercetin
      concentration was 52 nmol/l after the baseline period, during which habitual
      diets were consumed, and it did not change significantly during the intervention.
      Interindividual variation in the plasma levels of hesperetin and naringenin was
      marked and, after the baseline and wash-out periods, and the low-vegetable diet,
      a majority of the samples had plasma flavanone levels below the limit of
      detection. After the high-vegetable diet, hesperetin and naringenin were
      detectable in 54 and 22% of all samples. Quercetin was detectable in nearly all
      samples after all study periods. CONCLUSION: Hesperetin, naringenin and quercetin
      are bioavailable from the diet, but the plasma concentrations of hesperetin and
      naringenin are poor biomarkers of intake.

PMID- 12209379
TI  - The need to review the Spanish recommended dietary energy and nutrient intakes.
AB  - BACKGROUND: In the last decade, research in the field of nutrition has grown both
      in width and depth, and has incorporated the advances of other scientific fields,
      like artificial intelligence theories. Specifically in the case of recommended
      nutrient intakes, the fuzzy theory is an interesting contribution to the
      development of a new concept for the recommendations. The recommended intakes
      have passed from avoiding deficiency status to preventing several pathological
      aspects and reducing risk factors. OBJECTIVE: To establish whether the
      recommended dietary intakes for Spain (IREs) must be reviewed, taking into
      account the current scientific state of the art. METHODS: We have compared IREs,
      published in 1994, with the recently published 'Dietary Reference Intakes' (DRIs)
      for the American and Canadian population, the 'Referenzwerte fur die
      Nahrstoffzufuhr' (DACH) for the German, Swiss and Austrian population. In
      addition, the main guidelines of the EURODIET criteria (Nutrition and Diet for
      Healthy Lifestyles), which was developed for the population of the European Union
      Member States, were taken into account. As an example, comparisons were made for
      the elderly population group, establishing differences and similarities between
      the different scientific communities and the adequacy of Spanish recommended
      intakes for energy and nutrients. RESULTS: Recommended intakes for folate,
      calcium and vitamins C, D and E are lower in the IREs and probably should be
      increased. Recommended intakes for nutrients which have not previously been
      included in the IREs, such as vitamin K, selenium, copper, chromium, molybdenum,
      manganese, phosphorus, sodium, potassium, and water need to be developed.
      CONCLUSIONS: The current recommended intakes for the Spanish population need to
      be reviewed in order to encompass current scientific knowledge. Moreover, the
      opportunity to include non-nutrients (bioactive compounds) should be considered.

PMID- 12209380
TI  - Losses of vitamin A and E in parenteral nutrition suitable for premature infants.
AB  - OBJECTIVE: To assess the bioavailability of vitamins A and E administered
      parenterally with either water-soluble or lipid-soluble preparations. STUDY
      DESIGN: A water soluble preparation (MVI Pediatric) administered with a glucose
      amino acid solution and a lipid soluble preparation (Vitalipid N Infant) infused
      with a lipid emulsion were subjected to phototherapy light, different flow rates,
      light protection, different tubing materials and tubing sizes, and concentrations
      in the effluents were determined. RESULTS: Recovery of retinol in glucose-amino
      acid solution was poor under all conditions (16-30% without; 21-42% with light
      protection tubing) and increased to 61% with polyethylene and to 44% with
      polyurethane tubings. Polyurethane tubings with reduced volume improved retinol
      delivery to 56%. Retinylpalmitate (Vitalipid) losses were low, with recovery of
      86 and 77% with and without light protection, respectively. Recoveries of alpha
      tocopherylacetate in GLUC-AA were 103-107% without and 94-102% with light
      protection and of alpha-tocopherol in LIPID 89% without and 85% with light
      protection. CONCLUSIONS: Parenteral vitamin A delivery is improved by the
      infusion of retinylpalmitate with lipids. Light protecting tubings provide only a
      marginal benefit with artificial light and none with phototherapy light.
      Polyethylene and polyvinylchloride tubings adsorb less retinol than polyurethane
      tubings. Small tubing diameters resulting in higher flow rates enhance retinol
      delivery.

PMID- 12209381
TI  - Plasma glucose and insulin reduction after consumption of breads varying in
      amylose content.
AB  - OBJECTIVE: Consumption of a meal high in amylose starch (70%) decreases peak
      insulin and glucose levels and area under the curve (AUC). The objective was to
      determine the amount of amylose necessary in a meal for the beneficial decrease
      in glucose or insulin to occur. DESIGN: Twenty-five subjects, 13 men (averaging
      88.1 kg, 41 y, and 27.9 body mass index) and 12 women (averaging 72.4 kg, 41 y
      and 27.1 body mass index) were given six tolerance tests in a Latin Square
      design: glucose alone (1 g glucose/kg body weight) and five breads (1 g
      carbohydrate/kg body weight) made with 70% amylose cornstarch, standard
      cornstarch (30% amylose), and blends of the two starches (40, 50 and 60% amylose
      starch). A standard menu was fed for 3 days. One subject withdrew from the study.
      RESULTS: Glucose, insulin and glucagon response to the carbohydrate loads was
      similar in men and women. Peak glucose response was lowest after the breads
      containing 50-70% amylose starch. AUC was significantly higher after the glucose
      load than after all bread loads. The lowest AUCs occurred after the 60 and 70%
      amylose starch breads. Insulin response and AUC were significantly lower after
      the 60 and 70% amylose starch breads than after the glucose or the other breads.
      CONCLUSION: Results indicate that the amylose content of the starch used in the
      acute meal needs to be greater than 50% to significantly reduce plasma glucose
      and insulin in men and women.

PMID- 12209382
TI  - Use of energy-dense formula for treating infants with non-organic failure to
      thrive.
AB  - OBJECTIVE: To evaluate if simply increasing the energy density of the formula
      will lead to increased energy intake and weight gain in infants with non-organic
      failure to thrive. DESIGN: In this hospital-based trial, 15 infants (mean age,
      7.6+/-1.4 months) with non-organic failure to thrive were fed a regular strength
      formula (2.8 kJ/ml) for 3 days and then switched to the same formula with a
      higher energy density (4.18 kJ/ml) for 3 days after a 2 day 'wash-out' period.
      Daily nude weights and energy intakes were recorded for the two 3 day periods.
      RESULTS: During feeding with the higher density formula, nine (60%) infants had a
      significant increase in their energy intake and weight gain (both P<0.02); four
      (27%) showed no change in energy intake and self-regulated their intake by
      decreasing the volume of feeds consumed to maintain energy intake; and two (13%)
      infants consumed a significantly reduced amount of energy (P<0.02). CONCLUSION:
      Increasing the energy density of the formula may provide a useful intervention to
      increase the weight gain and energy intake of most infants with non-organic
      failure to thrive.

PMID- 12209383
TI  - Plasma deoxycholic acid concentration is elevated in postmenopausal women with
      newly diagnosed breast cancer.
AB  - OBJECTIVE: High concentrations of plasma deoxycholic acid (DCA) are found in
      human breast cyst fluid and it has been hypothesised that this may be related to
      risk of breast cancer. The aim of this pilot study was to ascertain whether
      plasma bile acid concentrations were greater in women with breast cancer. DESIGN:
      A case-control study comparing postmenopausal women with breast cancer with
      healthy controls was conducted. SUBJECTS: Twenty Caucasian postmenopausal breast
      cancer patients were recruited at the time of diagnosis together with 20 healthy
      controls matched for age and body mass index. Exclusion criteria included any
      treatment for breast cancer, use of hormone replacement therapy in the last 12
      months, diabetes mellitus, a history of liver or gall bladder disease or abnormal
      liver function. MEASUREMENTS: Fasting plasma bile acid concentrations were
      determined by gas-liquid chromatography/mass spectrometry. RESULTS: The mean
      plasma DCA concentration was 52% higher (P=0.012) in patients with breast cancer
      compared with controls. CONCLUSION: These results support the hypothesis that DCA
      may be involved in the aetiology of breast cancer.

PMID- 12209384
TI  - In defense of the Mediterranean diet.

PMID- 12209386
TI  - Differences in levels of heterozygosity in populations of the common gudgeon
      (Gobio gobio, Cyprinidae) among adjacent drainages in Central Europe: an effect
      of postglacial range dynamics?
AB  - Twenty-nine allozyme loci analyzed in 295 common gudgeons (Gobio gobio) from the
      Rhine, the upper Danube and the Elbe river systems revealed variability measures
      of P = 0.590, H(e) = 0.066, and G(ST) = 0.1415. Gene flow was estimated at N(e)m
      = 1.88 over 223 river km in the Danube basin, and at N(e)m = 1.96 over 300 river
      km in the Rhine system. Isolation-by-distance was not observed. Danubian gudgeons
      proved significantly more heterozygous (H(e) = 0.106) than those from the Rhine
      (H(e) = 0.057) or the Elbe drainages (H(e) = 0.029). Nine polymorphic enzymes
      contributed to this difference, which probably indicates dispersal bottlenecking
      of the postglacial immigrants into the Atlantic drainages of the study area.
      Refugial bottlenecking of gudgeons from Atlantic drainages in a Pleistocene
      refuge located in oceanic northwest Europe also seems possible. Slightly deeper
      genetic lineages in the Danube (G(ST) = 0.0859) than in the Rhine (G(ST) =
      0.0793) agree with this explanation, as does the greater mean genetic distance
      among pairs of population samples from the Danube (D = 0.0138) than from the
      Rhine (D = 0.0054). A genetic distance of D = 0.0085 separated Rhenish and
      Danubian gudgeons.

PMID- 12209387
TI  - Natural and artificial secondary contact in brown trout (Salmo trutta, L.) in the
      French western Pyrenees assessed by allozymes and microsatellites.
AB  - Analysis of allozyme polymorphism in brown trout (Salmo trutta) populations from
      south-western France shows that two genetically differentiated wild forms
      (characterised by the LDH-C1*100 and 90 alleles) introgress in this area. As
      allozymes could not evaluate the impact of stocking in the Atlantic basin,
      microsatellites have been necessary to detect the influence of hatchery fish and
      to confirm that the observed structure was natural. Microsatellites confirm the
      distinctness of the two wild forms based on allozyme loci. This situation
      provides a new example of secondary contact for this species in the Atlantic
      basin, with various levels of mixing being seen between the two population
      groups. The origin of these forms is discussed in the light of previous studies
      concerning modern and ancestral Atlantic trout (Hamilton et al, 1989) and
      lineages stemming from different glacial refuges (Garcia Marin et al, 1999; Weiss
      et al, 2000). This local analysis provides new insights in defining the
      evolutionary history of this species and confirms the important role of
      glaciation events in this history.

PMID- 12209388
TI  - Combining DNA sequences and morphology in systematics: testing the validity of
      the dragonfly species Cordulegaster bilineata.
AB  - Morphological and molecular techniques are rarely combined when answering
      questions of taxonomic validity. In this study, we combine morphological
      techniques with DNA sequences to determine the validity of the dragonfly species
      Cordulegaster bilineata. The two dragonfly species C. bilineata and C. diastatops
      are very similar in size, body color, and morphological characters, and due to
      these similarities, the status of C. bilineata as a valid species is in question.
      In this study we compare morphological measurements of males and internal
      transcribed spacer 1 (ITS-1) sequences of rDNA between the two taxa. The hamule
      measurements (where copulation occurs) of males show little difference between
      the taxa in question, but the anal appendage measurements (where the male first
      contacts the female) show marked divergence between the two taxa. Cluster
      analysis with these anal appendage measurements correctly assigns almost all
      individuals measured into their respective taxon. PCR amplification products of
      ITS-1 display a approximately 50 bp size difference between C. bilineata (n = 4)
      and C. diastatops (n = 5) regardless of collection site. Sequence data for these
      amplifications show 51 bp missing in one locus in the ITS-1 of C.
      bilineatarelative to C. diastatops. A lone population of C. diastatops from
      Wisconsin has three individuals with ITS-1 products that match the size of both
      C. bilineata and C. diastatops. One individual from this population appears to
      yield two ITS-1 amplification products that match both C. bilineata and C.
      diastatops. Although this population may be evidence for hybridization between
      the two taxa, such hybridization is not necessarily sufficient to disqualify the
      validity of a separate species designation for C. bilineata. Morphology and ITS-1
      sequences depict a high degree of divergence that is consistent with species
      level differences.

PMID- 12209390
TI  - Population genetic structure in a Mediterranean pine (Pinus pinaster Ait.): a
      comparison of allozyme markers and quantitative traits.
AB  - F-statistics were employed to analyse quantitative and allozyme variation among
      19 native populations of maritime pine (Pinus pinaster Ait.). Fourteen
      polymorphic allozyme loci were used to provide an empirical basis for
      constructing a null hypothesis to test natural selection as a determinant of
      quantitative evolution in stem form, total height growth and survival at 30 years
      old. Hidden biases, that may result in a difference between quantitative (Q(ST))
      and allozyme (F(ST)) differentiation which are not because of the action of
      natural selection, were avoided by comparing pairs of populations using linear
      models. All quantitative traits showed higher differentiation than allozymes. The
      highest divergence was found in stem form, whereas divergences in total height
      and survival were significantly lower. Differential adaptation to regional and
      local patterns of precipitation, temperature and soil type seem to be the best
      explanation of the different structure found in quantitative traits and allozyme
      loci. Possible bias in the estimation of Q(ST) due to the level of quantitative
      within-population diversity and the role of adaptation of maritime pine after the
      last glaciation to highly diverse ecological conditions are discussed with
      special reference to the actual geographical structure of gene diversity in the
      species' native range.

PMID- 12209389
TI  - Patterns of genetic variation in Pinus chiapensis, a threatened Mexican pine,
      detected by RAPD and mitochondrial DNA RFLP markers.
AB  - Pinus chiapensis (Pinaceae) is a large conifer, endemic to central and southern
      Mexico and north-western Guatemala. In order to assess the extent of genetic
      variation within and between populations of this species, samples were obtained
      from throughout the natural range and analysed using random amplified polymorphic
      DNA (RAPD) and mtDNA RFLPs markers. Probes for the CoxI mitochondrial gene
      enabled two mitotypes to be observed. Populations from the eastern and western
      limit of the range of the species were fixed for one mitotype ('A'), whereas two
      populations distributed near the centre of the range were fixed for another
      ('B'). When the samples were screened with eight 10-mer RAPD primers, a total of
      12 polymorphic bands were detected. The proportion of polymorphic bands was
      unusually low (24.5%) compared with other tree species. AMOVA analysis indicated
      that a significant proportion of the variation (P < 0.002) was distributed
      between populations; the extent of population differentiation detected (Phi(st) =
      0.226; G(ST ) = 0.194) was exceptionally high for a pine species. Pair-wise
      comparison of Phi(st) values derived from AMOVA indicated that populations were
      significantly (P < 0.05) different from each other in virtually every case. These
      results are interpreted in the context of the evolutionary history of the
      species, and the implications for its in- and ex situ conservation are discussed.

PMID- 12209391
TI  - Hierarchical analysis of genetic structure in Spanish donkey breeds using
      microsatellite markers.
AB  - The hierarchical population structure of five, native-Spanish donkey breeds
      (Andaluza, Catalana, Mallorquina, Encartaciones and Zamorano-Leonesa) has been
      studied using F-statistics. In addition, nine Moroccan asses and 24 Merens breed
      horses were included in the analysis. Data came from 15 DNA microsatellites. The
      analysis shows that Spanish donkeys are substructured at both hierarchical levels
      studied, among breeds and within breeds (between subpopulations). In the whole
      population, the deficit of heterozygotes was estimated to be about 21%. The
      fixation indices corresponding to differences between breeds, subpopulations
      within breeds, and within subpopulations were estimated to be 6.4%, 3.5% and
      3.0%, respectively. The dendrogram obtained shows that the Andaluza and the
      Moroccan ass form a separate cluster from the northern Spanish breeds (Catalana,
      Encartaciones, Mallorquina and Zamorana-Leonesa). These groupings coincide with
      those obtained from historical and archaeological data.

PMID- 12209392
TI  - Male fitness of oilseed rape (Brassica napus), weedy B. rapa and their F(1)
      hybrids when pollinating B. rapa seeds.
AB  - The likelihood that two species hybridise and backcross may depend strongly on
      environmental conditions, and possibly on competitive interactions between
      parents and hybrids. We studied the paternity of seeds produced by weedy Brassica
      rapa growing in mixtures with oilseed rape (B. napus) and their F(1) hybrids at
      different frequencies and densities. Paternity was determined by the presence of
      a transgene, morphology, and AFLP markers. In addition, observations of flower
      and pollen production, and published data on pollen fertilisation success, zygote
      survival, and seed germination, allowed us to estimate an expected paternity. The
      frequency and density of B. napus, B. rapa, and F(1) plants had a strong
      influence on flower, pollen, and seed production, and on the paternity of B. rapa
      seeds. Hybridisation and backcrossing mostly occurred at low densities and at
      high frequencies of B. napus and F(1), respectively. F(1) and backcross offspring
      were produced mainly by a few B. rapa mother plants. The observed hybridisation
      and backcrossing frequencies were much lower than expected from our compilation
      of fitness components. Our results show that the male fitness of B. rapa, B.
      napus, and F(1) hybrids is strongly influenced by their local frequencies, and
      that male fitness of F(1)hybrids, when pollinating B. rapa seeds, is low even
      when their female fitness (seed set) is high.

PMID- 12209393
TI  - Contact zones between chromosomal races of Mus musculus domesticus. 3. Molecular
      and chromosomal evidence of restricted gene flow between the CD race (2n = 22)
      and the ACR race (2n = 24).
AB  - The contact zone between the Ancarano (ACR; 2n = 24) and Cittaducale (CD; 2n =
      22) races of Mus musculus domesticus was studied. We used chromosomes and
      mitochondrial DNA (mtDNA) sequences of the control region as genetic markers to
      detect introgression between races. In total, 76 mice were trapped at 17
      localities. Cytogenetic analysis was performed on 73 mice. A segment of the
      control region (468 bp) was sequenced in 41 specimens. The two races are
      distributed parapatrically and the contact zone was identified inside a village
      (Pizzoli). No mixed population was found in the study area. The contact zone does
      not correspond to any geographical or ecological barrier but is located in a zone
      of potentially high density of mice. The sequence analysis clearly demonstrates
      genetic differentiation between races (1.4% of sequence divergence).
      Hybridization is rare. Evidence of introgression was found in two individuals in
      the contact zone: one individual of the ACR race carries a metacentric belonging
      to the CD race, while another ACR individual carries a CD-like haplotype. In
      these ecological conditions, the observed distribution pattern and the very low
      level of hybridization suggest the presence of a premating mechanism of
      reproductive isolation.

PMID- 12209394
TI  - Genetics of fluctuating asymmetry in pupal traits of the speckled wood butterfly
      (Pararge aegeria).
AB  - Fluctuating asymmetry (FA), small random differences between left and right, has
      been extensively used as a measure of individual quality, though its usefulness
      in that respect is controversial. Whether FA is heritable has implications for
      sexual selection theory and for its usefulness as an indicator of stress.
      Heritability (h(2)) of FA is, however, difficult to estimate precisely and
      reliably. Here we report h(2)s of FA for two pupal traits in the speckled wood
      butterfly (Pararge aegeria). We used a restriction error maximum likelihood
      (REML) analysis in combination with a jackknife procedure to analyse a large
      mixed offspring-parent/half-sib/full sib data set. A five-generation selection
      experiment provided a second set of narrow sense h(2)s. Narrow sense h(2)s were
      not significant and on average -0.029 (REML-analysis) and 0.031 (selection
      experiment) for the pupal segment covering the fore leg (LEG) and 0.057 and 0.004
      for a SPOT on that segment. Estimated percentage dominance variances were 0.057
      (LEG) and 0.027 (SPOT) and not significantly different from 0. The h(2) estimates
      had been slightly increased by cage effects. Average FA for LEG after five
      generations of selection were higher in the high lines than in the low lines, and
      the control lines were in between. No difference in FA between lines was found
      for SPOT. Although differences between lines were not significant, a slight h(2)
      (<3%) for LEG could not be excluded. The genetic effect was, however, small
      compared with the effect of foodplant quality. Larvae grown on foodplants that
      were not watered enough for good growth showed significantly higher FA for LEG,
      but not for SPOT, compared with larvae grown on good foodplants.

PMID- 12209398
TI  - It were to be wished the flaws were fewer...but the main thing is, does it hold
      good measure?

PMID- 12209399
TI  - Appropriate indicators for injury control?
AB  - Indicators are valuable tools used to measure progress towards a desired health
      outcome. Increased awareness of the public health burden due to injury has lead
      to a concomitant interest in monitoring the impact of national initiatives that
      aim to reduce the size of the burden. Several injury indicators have now been
      proposed. This study examines the ability of each of the suggested indicators to
      reflect the nature and extent of the burden of non-fatal injury. A criterion
      validity, population-based, prospective cohort study was conducted in Brisbane, a
      sub-tropical Metropolitan City on the eastern seaboard of Australia, over a 12
      month period between 1 January and 31 December 1998. Neither the presence of a
      long bone fracture nor the need for hospitalisation for 4 or more days were
      sensitive or specific indicators for 'serious' or major injury as defined by the
      'Gold Standard' Injury Severity Score (ISS). Subsequent analysis, using other
      public health outcome measures demonstrated that the major component of the
      illness burden of injury was in fact due to 'minor' not serious injury. However,
      the suggested indicators demonstrated low sensitivity and specificity for these
      outcomes as well. The results of the study support the need to include at least
      all hospitalisations in any population-based measure of injury and not attempt to
      simplify the indicator to a more convenient measure aimed at identifying just
      those cases of 'serious' injury.

PMID- 12209400
TI  - Measure for measure: the quest for valid indicators of non-fatal injury
      incidence.
AB  - In this edition of Public Health, McClure and colleagues report on research that
      considered the criterion validity of indicators based on serious long bone
      fracture and length of stay in hospital. They found that neither were sensitive
      or specific indicators for serious injury as defined by an Injury Severity Score
      (ISS) of 16 or more. They contend that their study findings ' em leader strongly
      support a return to a measure similar in intent to that encapsulated in the
      original UK Green Paper em leader '. We contend that their analysis does not
      provide any empirical evidence to support their view that there should be a
      return to the Green Paper: Our Healthier Nation indicator. Furthermore, we
      consider the analyses that they carry out to validate both the Saving Lives: Our
      Healthier Nation and the serious long bone fracture indicators are flawed. We
      agree that national (or state) indicators are very influential. They encourage
      preventive action and resource use aimed at producing favourable changes to these
      indicators. However, each of the four non-fatal indicators considered in their
      analysis have problems. Formal validation of existing indicators is necessary and
      the following aspects of validity should be addressed: face; criterion;
      consistency; and completeness and accuracy of the source date. Taking into
      account the current national data systems in England, possible options for one or
      more national non-fatal unintentional injury indicators have been proposed in our
      paper. Furthermore, the International Collaborative Effort on Injury Statistics
      (ICE) Injury Indicators Group is about to embark on the development of a
      strategic framework for the development of valid indicators of non-fatal injury
      occurrence.

PMID- 12209401
TI  - Predisposing and precipitating factors for falls among older people in
      residential care.
AB  - Falls and their consequences are serious health problems among older populations.
      To study predisposing and precipitating factors for falls among older people in
      residential care we used a cross-sectional study design with a prospective follow
      up for falls. Fifty-eight women and 25 men, with a mean age of 79.6 y, were
      included and prospectively followed up regarding falls for a period of 1 y after
      baseline assessments. All those who fell were assessed regarding factors that
      might have precipitated the fall. The incidence rate was 2.29 falls/person years.
      Antidepressants (selective serotonin reuptake inhibitors, SSRIs), impaired vision
      and being unable to use stairs without assistance were independently associated
      with being a 'faller'. Twenty-eight (53.8%) of the fallers suffered injuries as a
      result of their falls, including 21 fractures. Twenty-seven percent of the falls
      were judged to be precipitated by an acute illness or disease and 8.6% by a side
      effect of a drug. Acute symptoms of diseases or drug side effects were associated
      with 58% of the falls which resulted in fractures. We conclude that SSRIs seem to
      constitute one important factor that predisposes older people to fall, once or
      repeatedly. Since acute illnesses and drug side-effects were important
      precipitating factors, falls should be regarded as a possible symptom of disease
      or a side-effect of a drug until it is proven otherwise.

PMID- 12209402
TI  - Inpatient hospital care for lumbar intervertebral disc disorders in Finland in
      relation to education, occupational class, income, and employment.
AB  - The object of the study was to describe socioeconomic and demographic
      determinants of inpatient hospital care for lumbar intervertebral disc disorders
      (LIDD) in Finland. Information from the 1996 Finnish Hospital Discharge Register
      was linked with the 1995 Population Census. Poisson regression analyses were made
      with the total and the gainfully employed workforce aged 20-64 y as reference.
      All 48 public and seven private acute care general hospitals treating LIDD
      patients in Finland. In the workforce, 4643 patients aged 20-64 y (3692 among the
      gainfully employed) were admitted to the hospital due to LIDD (ICD-10: M51.1
      M51.9) in 1996. About one-half were treated surgically. The duration of
      unemployment in 1995 was inversely associated with hospitalisation for LIDD in
      1996, allowing for age, sex, education and personal income (unemployed for 12
      months vs 0 months: rate ratio 0.66; 95% CI 0.57-0.77). Among those employed for
      12 months in 1995, the level of education was inversely associated with the
      hospital admission rate. The rate was also higher in manual occupations as
      compared with the upper white-collar employees. The associations were clearer
      among the medically than the surgically treated patients. Hospitalisation for
      back disorder was, however, less common in the lowest income group as compared
      with the highest (0.65; 0.57-0.77) allowing for education, occupational class,
      age and sex. Women were less often admitted to the hospital than men, allowing
      for the socioeconomic factors (0.83; 0.77-0.90). When indicated by education or
      occupation, low socioeconomic status was associated with a relatively high rate
      of inpatient hospital care for LIDD. When indicated by personal income, the
      situation was the reverse. Unemployment and female gender predicted a relatively
      low rate of hospitalisation.

PMID- 12209403
TI  - Birthplace and social characteristics as risk factors for acute myocardial
      infarction in the province of Halland, Sweden.
AB  - The aim of the study was to explore the impact of birthplace and socio-economic
      characteristics on the risk of acute myocardial infarction (AMI) in a rural
      Swedish province. A case control study was performed and cases were all patients
      30-72-y-old treated for the first time for an AMI during 1980-1992 and identified
      in a computerised hospital register. Three controls for each case were randomly
      selected from the national population register and were matched for gender, age
      and municipality. Birthplace ie within or outside the province, and a variety of
      socio-economic background factors were determined for cases and controls. The
      study comprised a total of 18 948 individuals including cases and controls.
      Altogether 4737 cases of AMI were identified whereof 3514 were men. Being born in
      the province was associated with the lowest risk for AMI in both sexes (RR=0.62,
      CI 0.57-0.67 for men and RR=0.61, CI 0.53-0.69 for women). A substantially
      reduced risk for men was found in farmers. In both sexes, high socio-economic
      status had a favourable effect on the risk to suffer an AMI. Being born in the
      province carried the lowest risk for AMI in both sexes and was independent of
      other tested socio-economic factors (income, education, occupation, and civil
      status). Province characteristics might be associated with this protective
      factor. Alternatively, migration as such might include unfavourable exposures
      that increase the risk for AMI among those who had moved to the province.

PMID- 12209404
TI  - Cardiovascular mortality focusing on socio-economic influence: the low-risk
      population of Halland compared to the population of Sweden as a whole.
AB  - The aim of the study was to investigate the relationship between mortality from
      cardiovascular diseases (CVD) and socio-economic status (SES) in Sweden and to
      estimate to what extent the difference between a province with low mortality and
      the rest of Sweden was dependent on socio-economic factors. A population-based
      retrospective study with a historical prospective approach was performed covering
      a 10-y period in the province of Halland, Sweden, as well as Sweden as a whole.
      Altogether 1,654,744 men and 1,592,467 women were included, of whom 45,394 men
      and 43,403 women were from Halland, distributed according to SES. Multivariate
      analysis with Poisson regression was used. Relative risks with 95% confidence
      intervals were calculated. Both men and women with a low SES showed a
      significantly higher risk of death from CVD in Sweden as a whole. The risk was
      23% higher for male blue-collar workers and 44% higher for female blue-collar
      workers when compared to their white-collar counterparts. The level of mortality
      in Halland was 14% lower compared to the country as a whole when only age was
      taken into account. When the socio-economic variable was also included, this
      figure was 8%. The results show the substantial significance of social
      differences with respect to CVD mortality. The effect of SES seems to be more
      important than that of geographical conditions when the latter are isolated from
      socio-economic influence.

PMID- 12209405
TI  - Care-related risk factors for chronic diabetic complications in developing
      countries: a case from Egypt.
AB  - This work was the second phase of a wider study aiming at defining a plan for the
      improvement of health care services for diabetic patients and to decrease the
      incidence of its complications. The aim of this phase of the study was to define
      preventable risk factors for chronic diabetic complications, especially care
      related factors. A total of 472 diabetic patients with chronic complications were
      compared with 528 control patients, free from complications, in a multicentric
      case-control study. Multivariate logistic regression analysis revealed that
      diabetic patients over 49 y of age, and female gender were more likely to develop
      chronic diabetic complications. Among clinical variables, type and duration of
      diabetes, glycemic control, and hypertension were significant predictors of
      diabetic complications. Regarding patient and system practices, non-health
      insurance, need of help to reach health care facility, irregularity of follow-up
      visits and attending more than one clinic for follow-up, sources of health
      information other than physician and nurse, non-practicing leisure physical
      activities, and smoking were statistically significant risk factors. The study
      helped to identify preventable risk factors for serious complications of
      diabetes. It also identified groups of patients who needed priorities of
      screening programmes for potential development of complications since they were
      likely to develop such type of complications.

PMID- 12209406
TI  - What are Pakistani women's experiences of antenatal carrier screening for beta
      thalassaemia in the UK? Why it is difficult to answer this question?
AB  - In the UK antenatal screening of Pakistani women for thalassaemia carrier status
      is commonplace. This paper describes our attempts to investigate women's
      experiences of such screening and the reasons why this proved difficult to do.
      These included a pregnancy per year and communications failure between different
      health professionals involved in antenatal haemoglobinopathy screening. These
      issues have implications for the way in which such screening is conducted and
      these are discussed.

PMID- 12209407
TI  - Referral patterns to a district Child Development Centre: 25 years experience.
AB  - This study describes the changes in referral patterns to a district Child
      Development Centre over 25 y. Referral information was collected prospectively
      for all referrals seen at the Child Development Centre at Northampton, UK, from
      1974 to 1998 inclusive. This unique data set records CDC usage over 25 y in the
      same district and was collected, until recently, by the same individual.
      Professional awareness and identification of complex developmental problems
      appeared to improve over the study period. The data show a gradual rise in
      referral rates to reach a plateau of between 5.5 and 7.2 referrals per 1000
      children under 5 per annum. This level of referral achieves almost complete
      ascertainment of childhood disability needing statutory assessment by the age of
      6 y. The increases in early referrals followed educational intervention with
      primary health care teams emphasising the importance of early identification and
      referral.

PMID- 12209410
TI  - Evaluation of three peripheral arteriovenous fistulas for hemodialysis access in
      dogs.
AB  - OBJECTIVE: To design and create 3 types of arteriovenous fistulas (AVF) in normal
      dogs, to monitor the dogs for secondary cardiovascular complications, and to
      verify adequacy of these fistulas for hemodialysis vascular access. STUDY DESIGN:
      Experimental study. ANIMALS: Four normal adult dogs. METHODS: Cadaveric
      dissections were performed, and surgical protocols were generated for carotid
      jugular (CJ), brachial-cephalic (BC), and distal caudal femoral-lateral saphenous
      anastomosis (DCFLS) AVF. Each surgical procedure was then performed in 2 live
      dogs. Echocardiography was performed at days 0, 1, 3, 7, 14, 28, and 56 to
      evaluate the dogs for evidence of volume overload secondary to AVF formation.
      Estimation of luminal diameter and confirmation of fistula patency were performed
      using percutaneous color Doppler ultrasound. At day 56, hemodialysis was
      performed using each fistula as a vascular access. RESULTS: No significant
      changes occurred in the echocardiographic variables over time. All fistulas were
      patent at day 56 with mean luminal diameters of 4.5 mm (CJ), 4 mm (BC), and 1.5
      mm (DCFLS). The BC fistula was superior for ease of needle placement and
      stabilization and provided adequate blood flow for clinical hemodialysis.
      CONCLUSIONS: Based on this short-term study, arteriovenous fistulas appear to be
      a safe and effective means for hemodialysis access in dogs. CLINICAL RELEVANCE:
      The arteriovenous fistulas described provide an alternative to the central venous
      catheters currently used for chronic hemodialysis access in dogs.

PMID- 12209411
TI  - Cardiopulmonary bypass in the cat.
AB  - OBJECTIVE: To assess the physiologic response to, and acute survival of, cats
      undergoing cardiopulmonary bypass (CPB) and to evaluate the efficacy of a
      commercial human pediatric oxygenator system on cats weighing less than 6 kg.
      STUDY DESIGN: Experimental study. ANIMALS: Six intact male cats METHODS: Cats
      were placed on cardiopulmonary bypass by cannulating the cranial and caudal vena
      cavae and the carotid artery. The pediatric CPB circuit was primed with 150 mL of
      a balanced crystalloid solution. Venous drainage was enhanced by a controlled,
      vacuum-assist system. A cross-clamp was placed on the ascending aorta and cardiac
      arrest was induced by antegrade infusion of a cold cardioplegia solution. After
      45 minutes of arrest time, the cross-clamp was removed and the cats were weaned
      off bypass and decannulated. No blood products were administered. Heart rate,
      mean arterial pressure (MAP), central venous pressure, arterial blood gas,
      hematocrit (HCT), total plasma protein concentration (TP), serum electrolyte
      concentrations, and activated clotting time (ACT) were measured at baseline
      period (BL), during CPB, 60 minutes after CPB (CPB 60) and 90 minutes after CPB
      (CPB 90). A complete blood count (CBC), blood chemistry profile, and urinalysis
      were performed at BL, during CPB, and CPB 90. Cats were euthanatized after CPB
      90. RESULTS: Cardiopulmonary bypass resulted in a significant (P <.05) decrease
      in mean HCT (18.0%) and TP (2.3 gm/dL) at CPB 90 when compared to BL (30.5% and
      6.0 gm/dL, respectively). The MAP at CPB 90 (54 mm Hg) was decreased from BL (94
      mm Hg). The ACT increased from a mean of 124 seconds to > 400 seconds with
      heparinization and was reversed to 300 seconds with protamine. Mean platelet
      counts decreased from BL (369,000 /microL) to CPB 90 (94,500 /microL). Mean white
      blood cell counts decreased from 13,200 /microL at BL to 2,200 /microL at CPB 90.
      Upon reperfusion, 1 cat fibrillated but was successfully defibrillated.
      CONCLUSIONS: Cardiopulmonary bypass was performed successfully in 6 cats weighing
      less than 6 kg. Acute survival to 90 minutes after CPB was achieved in all 6 cats
      CLINICAL RELEVANCE: The ability to perform CPB in the cat may allow intracardiac
      repair of various heart defects in this species.

PMID- 12209412
TI  - Dorsal laminectomy for caudal cervical spondylomyelopathy: postoperative recovery
      and long-term follow-up in 20 dogs.
AB  - OBJECTIVE: To evaluate the postoperative morbidity and long-term outcome of dogs
      after dorsal laminectomy for caudal cervical spondylomyelopathy (CCSM). STUDY
      DESIGN: Retrospective study. SAMPLE POPULATION: Twenty dogs with CCSM. METHODS:
      Medical records of dogs treated by dorsal laminectomy for CCSM at North Carolina
      State University and Colorado State University between 1989 and 1999 were
      reviewed. Information on signalment, onset, progression and duration of clinical
      signs, diagnostic testing, sites of dorsal laminectomy, postoperative
      complications, length of hospitalization, and the ambulatory status on discharge
      was recorded. A minimum follow-up of 7 months was required for inclusion in the
      study. Neurologic status was graded (0 to 5) preoperatively, 2 days after
      surgery, and at the time of the study (final score). Improvement or worsening of
      the neurologic status was assessed by comparison of different scores for each
      dog. Additional follow-up information was obtained by means of a detailed
      telephone questionnaire directed at both the owner and referring veterinarian.
      RESULTS: Mean duration of clinical signs before surgery was 4.9 months. At
      admission, 15 dogs were ambulatory and 5 were nonambulatory. Neurologic status
      worsened in 70% of dogs 2 days after surgery but improved in all but 1 dog over
      the long term. Mean time to optimal recovery was 3.6 months. Long-term follow-up
      ranged from 7 months to 9 years (mean +/- SD, 3.2 +/- 2.4 years). Four dogs had
      confirmed recurrence; 2 other dogs may have had recurrence. CONCLUSIONS: Dorsal
      cervical laminectomy is an effective treatment for CCSM in those dogs with dorsal
      compression or multiple sites of involvement. CLINICAL RELEVANCE: Although most
      dogs' neurologic status transiently worsened after surgery, long-term outcome and
      recurrence rates were comparable to those seen with other surgical techniques for
      CCSM.

PMID- 12209413
TI  - A retrospective study of 40 dogs with polyarthritis.
AB  - OBJECTIVE: To characterize the epidemiologic, clinical, laboratory, and
      radiographic findings from dogs with polyarthritis (PA). STUDY DESIGN:
      Retrospective clinical study. SAMPLE POPULATION: Forty dogs. METHODS: Medical
      records of 40 dogs with a diagnosis of PA were reviewed. Retrieved data included
      breed, age at admission, sex, weight, clinical signs, and the results of synovial
      fluid analysis, complete blood count, serum chemistry profile, urinalysis,
      serologic screening tests for infectious diseases, and radiographic examination
      of affected joints. RESULTS: The incidence of PA was 0.37%. Twenty-nine breeds
      were represented; 16 dogs were male, and 24 were female. Mean body weight was
      20.1 +/- 15 kg. The mean age at admission was 5.6 +/- 4 years. Eighty percent of
      dogs with PA had difficulty or reluctance walking, 35% were lame, 33% had
      spontaneous vocalization without any obvious reason, 20% had exercise
      intolerance, 18% were febrile, and 7.5% had an inability to rise or move. Joint
      pain was identified in 40% of dogs. Synovial fluid color varied from colorless
      (36%) to yellow-tinged (36%) or hemorrhagic (28%). Synovial fluid mean cell count
      varied from 10 cells (400x) to 50 cells (1,000x). Leukocytosis occurred in 59% of
      the dogs and was more frequently identified in dogs with very severe synovial
      inflammation. Thirty-one percent of affected dogs were anemic. Serum biochemical
      profiles were considered abnormal in 13% of the dogs. Joint radiography did not
      identify erosive arthritis. CONCLUSIONS: PA is a common cause of locomotor
      abnormalities in dogs; however, true lameness and articular pain are not common
      clinical findings in dogs with PA. CLINICAL RELEVANCE: PA should be considered in
      the differential diagnosis for all dogs with difficulty walking.

PMID- 12209414
TI  - Juvenile pubic symphysiodesis in dysplastic puppies at 15 and 20 weeks of age.
AB  - OBJECTIVE: To examine the effects of juvenile pubic symphysiodesis (JPS) on hip
      joint conformation, hip laxity, gait, and the development of degenerative joint
      disease (DJD) in dysplastic puppies operated at 15 and 20 weeks of age. STUDY
      DESIGN: Randomized controlled prospective study. ANIMALS-Eighteen female hound
      puppies with increased hip laxity. METHODS: Puppies were randomized to 1 of 4
      treatment groups: JPS at 15 weeks of age (n = 6), sham-operated control at 15
      weeks of age (n = 3), JPS at 20 weeks of age (n = 6), and sham-operated control
      at 20 weeks of age (n = 3). Hip extension with pain scoring, Ortolani palpation,
      hip reduction angle measurement (HRA), PennHIP radiography (University of
      Pennsylvania) with measurement of distraction index, Norberg angle measurement,
      and transverse computed tomographic imaging to measure acetabular angle (AA) and
      dorsal acetabular rim angle (DARA), were tested preoperatively, and at 1 and 2
      years of age. RESULTS: JPS resulted in significant changes in AA, HRA, DARA, and
      conversion to Ortolani negative status. Larger and more rapid changes in hip
      conformation were seen when surgery was performed at 15 weeks of age. No
      significant changes were identified in control dogs. Twenty-five percent of JPS
      dogs developed DJD whereas 83% of control dogs developed DJD. CONCLUSIONS: JPS
      resulted in significant improvements in hip joint conformation and hip laxity in
      dysplastic puppies treated at 15 and 20 weeks of age. Improvements in
      conformation were significantly greater when surgery was performed at 15 weeks of
      age. CLINICAL RELEVANCE: JPS appears to be a promising treatment for hip
      dysplasia and is a safe and technically simple procedure to perform.

PMID- 12209415
TI  - A comparison of ultra-high-molecular weight polyethylene cable and stainless
      steel wire using two fixation techniques for repair of equine midbody sesamoid
      fractures: an in vitro biomechanical study.
AB  - OBJECTIVE: To compare the monotonic tensile and fatigue strength of 16-gauge
      stainless steel wire (SSW) to ultra-high-molecular weight polyethylene (UHMWPE)
      cable using a transfixed cerclage technique in an in vitro midbody sesamoid
      osteotomy model. Endoscopic modifications to Martins transfixed cerclage
      technique were developed. A new suture technique of fixation was compared with
      the transfixed cerclage technique by measuring gap formation after cyclic
      testing. STUDY DESIGN: An in vitro biomechanical paired equine cadaver limb
      study. SAMPLE POPULATION: Twenty-one paired cadaveric adult equine forelimbs.
      METHODS: Uniaxial medial midbody sesamoid osteotomies were created in paired
      adult equine forelimbs. Monotonic tensile strength was measured on 10 forelimbs
      repaired by a transfixed cerclage technique using wire or cable. Fatigue testing
      to failure was performed on 4 forelimbs repaired using the transfixed cerclage
      technique by cycling the limbs between 500 N and 2,000 N. The limbs were
      initially repaired with wire, cycled until the wire broke, then repaired with
      cable and cycled again to failure. Fatigue testing for gap displacement was
      performed on 8 limbs repaired with either the transfixed cerclage technique or
      the suture technique. Limbs were cycled between 500 N and 2,000 N for 10,000
      cycles. The limbs were repaired with wire initially, tested, and then repaired
      with cable and tested again. Twenty-two limbs were used for mechanical testing.
      The remaining limbs (20) were used to develop and practice the endoscopic
      transfixed cerclage (10 limbs) and suture (10 limbs) techniques. RESULTS:
      Ultimate tensile strength (UTS) of UHMWPE cable constructs was 34% greater than
      the UTS of SSW constructs. Fatigue strength was 2 to 20 times greater for UHMWPE
      cable constructs than SSW constructs. Separation of fragments was 153% less for
      limbs repaired by the suture technique compared with those repaired by the
      transfixed cerclage technique. CONCLUSIONS: UHMWPE cable shows promise for this
      clinical application because of its greater tensile and fatigue strength. The
      newly described suture technique significantly reduced gap formation compared
      with the transfixed cerclage technique. Osteotomy gap formation occurred early in
      cycling, suggesting that rigid support in the form of a cast may be needed during
      the early postoperative period for wiring techniques. CLINICAL RELEVANCE:
      Clinical testing of UHMWPE cable should eliminate problems of wire breakage seen
      with SSW. The endoscopic transfixed cerclage technique can be used by surgeons
      familiar with arthroscopic surgery. However, the suture technique needs to be
      tested in vivo to determine whether there is a clinical advantage compared with
      the transfixed cerclage technique.

PMID- 12209416
TI  - Use of a hydro-pool system to recover horses after general anesthesia: 60 cases.
AB  - OBJECTIVE: To report complications observed using a hydro-pool recovery system
      after general anesthesia in horses. STUDY DESIGN: Retrospective study. ANIMALS:
      Sixty horses. METHODS: Retrospective review of the medical records and quality of
      recovery from anesthesia of 60 horses that had surgical or diagnostic procedures
      under general anesthesia. RESULTS: Mean total anesthesia time was 182 minutes
      (range, 25 to 390 minutes). Mean time in the hydro-pool was 108 minutes (range,
      20 to 270 minutes). One horse that had bilateral rear limb extensor weakness
      while recovering in a padded recovery stall was moved to the hydro-pool and
      maintained for 12 hours. Ten horses developed some pulmonary edema; in 3 horses,
      the signs of pulmonary edema were severe; and 1 horse died from related
      complications. One horse developed septic arthritis of an operated stifle joint,
      and 2 horses developed incisional infections. Two horses incurred multiple skin
      abrasions on the distal aspect of their limbs during violent attempts to leave
      the pool. CONCLUSIONS: A hydro-pool system was useful for recovering horses from
      general anesthesia when difficult recoveries were anticipated because of the
      horse's injury, size, demeanor, duration of anesthesia, or risk of further
      injury. Recovery using the hydro-pool was more time and labor intensive than a
      standard stall recovery. Pulmonary edema that required treatment was a serious
      complication that occurred in 17% of the horses. Careful closure of the skin with
      cyanoacrylate glue and pressure from bandages were used to prevent postoperative
      incisional infections. CLINICAL RELEVANCE: A hydro-pool system is a useful method
      for recovering horses from general anesthesia when difficult recoveries are
      anticipated.

PMID- 12209417
TI  - Medial patellar ligament splitting for the treatment of upward fixation of the
      patella in 7 equids.
AB  - OBJECTIVE: To describe a surgical technique for splitting the proximal third of
      the medial patellar ligament (MPL) in horses and ponies with upward fixation of
      the patella (UFP), and to report outcome. STUDY DESIGN: Prospective clinical
      study. SAMPLE POPULATION: Four horses and 3 Shetland ponies. METHODS: With
      ultrasound guidance, the proximal third of the MPL was split by percutaneous use
      of a no. 15 scalpel blade. The rationale for this surgical procedure was to
      induce a localized desmitis with subsequent ligament thickening. No anti
      inflammatory drugs were administered, and horses and ponies were exercised the
      day after surgery. Clinical, radiographic and ultrasonographic follow-up
      evaluation was obtained. RESULTS: No short-term or long-term complications were
      observed, and no patients had clinical signs of UFP after surgery. This clinical
      effect was attributed to a 2- to 3-fold increase in size of the proximal part the
      MPL from an induced localized desmitis. CONCLUSIONS-Percutaneous splitting of the
      proximal third of the MPL resolved UFP in equids. CLINICAL RELEVANCE: Splitting
      of the proximal third of the MPL is effective for treatment of UFP and allows
      rapid return to normal activity.

PMID- 12209418
TI  - A comparison of the accuracy and safety of vertebral body pin placement using a
      fluoroscopically guided versus an open surgical approach: an in vitro study.
AB  - OBJECTIVE: To compare the safety and accuracy of Steinmann pin placement in
      vertebral bodies T10 through L7 using either an open or closed fluoroscopic
      method. STUDY DESIGN: In vitro radiographic and anatomic study. ANIMALS: Ten
      medium-sized canine cadavers. METHODS: Cadavers were randomly assigned to 2
      groups: open and closed. Steinmann pins were placed in vertebral bodies through a
      standard dorsal incision in the open group and percutaneously with the aid of
      fluoroscopy in the closed group. Pins were placed bilaterally in vertebral bodies
      T10 through L7 at approximately 30 degrees from horizontal and driven to a
      uniform depth. Necropsies were performed to examine potential pulmonary,
      vascular, or neurological trauma as a result of pin placement. Spines were cross
      sectioned through intervertebral disc spaces, and radiographs were performed to
      evaluate accuracy of pin placement. Descriptive statistics were determined for
      pin angle, percentage of bone purchase, and penetration length. Means of interest
      between groups were compared using a Student t test. Complication incidence was
      compared using Chi;(2) analysis. Significance was P <.05. RESULTS: Mean pin
      insertion angle was significantly different than 30 degrees for the open group in
      thoracic and lumbar vertebrae and for the closed group in thoracic vertebrae.
      Mean pin insertion angle for all vertebrae was significantly greater than 30
      degrees for the open group. Mean pin penetration distance in each vertebra was
      significantly different between groups with the closed group having less
      penetration and lower variance. Both groups were significantly different from the
      ideal penetration distance. The mean percentage of bone purchase was greater in
      the closed group for all vertebrae except T10 and T11. The complication incidence
      was significantly greater in the open group for thoracic vertebrae. CONCLUSION
      AND CLINICAL RELEVANCE: The results of this study suggest that a closed technique
      for placement of Steinmann pins in lumbar vertebrae for use in external skeletal
      fixation is a reasonable and safer alternative to the traditional open technique.
      Use of either technique in thoracic vertebrae should be avoided.

PMID- 12209419
TI  - The role of arthroscopic bursectomy in the treatment of trochanteric bursitis.
AB  - The use of arthroscopy to treat recalcitrant trochanteric bursitis is reported
      and its role in treating this common clinical entity is discussed. During a 7
      year period, 27 patients underwent this procedure. All patients complained of
      recurrent lateral hip pain despite at least 2 localized injections with
      corticosteroids. Minimum follow-up was 1 year, and the cases of 22 patients were
      reviewed after 5 years. Twenty-three of the 27 patients had good or excellent
      results immediately following the procedure and experienced no complications. At
      1 year, only 1 patient had experienced symptom recurrence, and at 5 years, only 2
      patients had had recurrence. All patients except 1 were satisfied with their
      outcome. Arthroscopically performed trochanteric bursectomy is a minimally
      invasive technique that appears to be both safe and effective for treating
      recalcitrant pain syndromes.

PMID- 12209420
TI  - Broken poly-L-lactic acid interference screw after ligament reconstruction.
AB  - The interference screw is a reliable method used to secure tendon to bone and
      bone to bone in ligament reconstruction. Historically, metal interference screws
      have been used for this purpose in both anterior cruciate ligament (ACL) and
      posterior cruciate ligament (PCL) reconstruction. However, several problems
      associated with the use of metal interference screws have led to the increasing
      use of bioabsorbable implants. Poly-L-lactic acid (PLLA) biodegradable
      interference screws have been used successfully for graft fixation in ligament
      reconstruction. Although adverse reactions have been reported with the use of
      biodegradable implants, late screw breakage is rare. To our knowledge no case
      exists of late screw breakage with bioabsorbable interference screws used in
      ligament reconstruction. We present one case in the setting of an ACL
      reconstruction and one with combined PCL and posterolateral corner
      reconstruction.

PMID- 12209421
TI  - Arthroscopic extraction of a drainage tube: solution for a troublesome problem.
AB  - We present a case of a foreign body retained in the knee joint after a hemovac
      tube was broken during removal at bedside. The foreign body was successfully
      extracted arthroscopically. Arthroscopy provides an excellent alternative in the
      management of this troubling complication, minimizing hospitalization and delay
      in recovery.

PMID- 12209422
TI  - Reconstruction of the anterior cruciate ligament with quadriceps tendon.
AB  - The author describes the technique he uses to reconstruct the anterior cruciate
      ligament (ACL) arthroscopically with autologous bone-quadriceps tendon (BQT)
      graft. The patellar bone is fixed in a femoral tunnel about 2.5 cm long, in a
      position that allows the tendinous extremity of the graft to appear on the extra
      articular exit of the tibial tunnel. The tibial tunnel is filled, making the
      integration of the tendon in the bone easier. The tendinous extremity of the
      graft is pulled by nonabsorbable wires, remaining strictly fixed by a staple or a
      screw in the anterointernal cortex of the tibia. When used in selected cases and
      when technical details are respected, this technique yields results similar to
      those obtained with the bone-patella tendon-bone (BPTB) graft. The functional
      recovery should be more careful with this technique than when the BPTB is used.
      Generally, less morbidity is seen with the BQT graft. The author believes that
      the BQT graft will be used more frequently, especially in ACL reconstruction, for
      patients whose jobs require kneeling or long periods of knee flexion, or in cases
      of low patella, patellar chondropathy, or tendinopathy of the patellar tendon.
      This technique may also be appropriate for revision surgeries.

PMID- 12209424
TI  - Degenerative arthritis arthroscopy and research.

PMID- 12209423
TI  - Anatomic tibial graft fixation using a retrograde bio-interference screw for
      endoscopic anterior cruciate ligament reconstruction.
AB  - The article describes a simple technique for anatomic anterior cruciate ligament
      (ACL) tibial graft fixation at the level of the intercondylar floor within a
      standard endoscopic tibial tunnel. Fixation is achieved with a retrograde
      positioned cannulated bio-interference screw delivered over a No. 5 permanent
      suture from a standard anteromedial portal. The screw is inserted into the tibial
      tunnel in an inside-out position, so that the head of the screw is flush with the
      intra-articular orifice of the tibial tunnel. Recent experimental, animal, and
      clinical studies have reported that the advantages of this type of anatomic graft
      fixation over nonanatomic tibial graft fixation include increased fixation
      strength, a more stable reconstruction through full knee range of motion, absence
      of postoperative tunnel expansion, and final biologic graft incorporation at or
      near the native ACL tibial insertion.

PMID- 12209425
TI  - Radiographic analysis of femoral tunnel position in postoperative posterior
      cruciate ligament reconstruction.
AB  - PURPOSE: The purpose of this study was to test the hypothesis that plain
      radiographs are accurate in assessing femoral tunnel positions in posterior
      cruciate ligament (PCL) reconstruction. TYPE OF STUDY: Cadaveric study. METHODS:
      Femoral tunnels were drilled in cadaveric distal femurs using standard techniques
      at the 12 o'clock, 1:30, and 3 o'clock positions in the left femora and at the 12
      o'clock, 10:30, and 9 o'clock positions in the right femora. At each of the three
      positions, a 9-mm tunnel was drilled with its anterior edge 2 mm posterior to the
      articular surface of the medial femoral condyle (MFC). Posterior or
      "malpositioned" tunnels were drilled with the anterior edge 11 mm posterior to
      the articular surface of the MFC. Four radiographs; a true lateral, a 10 degrees
      externally rotated lateral, a 10 degrees internally rotated film in the sagittal
      plane, and an anteroposterior (AP) radiograph were then taken of each tunnel with
      a radiopaque dilator in the tunnel. All radiographs were analyzed with the 4
      quadrant method (4 is the posterior quadrant) and the ratio method (0 is anterior
      and 1 is posterior). The AP radiograph was measured using a new technique, the
      intersection of the angle of a line through the center of the femoral tunnel and
      a line placed tangential to the femoral condyles. RESULTS: Means were calculated
      for each of the 6 tunnel positions on the 4 radiographs (lateral, external
      rotation, internal rotation, and AP). Of the 15 comparisons among tunnel
      postions, 13 could be discriminated using the lateral and AP radiographs. The
      high-anterior (HA) (12 o'clock position) could not be differentiated on any
      radiograph from the high-posterior (HP) (12 o'clock position). The internally
      rotated lateral radiograph could discriminate the midanterior (MA) (1:30 and
      10:30 positions) from the low-anterior (LA) (the 3 and 9 o'clock positions).
      CONCLUSIONS: Three radiographs; the AP, lateral, and internally rotated lateral,
      can be used to detect a significant difference in the majority of tunnel
      locations. The tunnel positions that could not be differentiated with these
      measurements were posterior and may not be clinically important. We concluded
      that a plain radiograph is an accurate indicator of PCL tunnel position.

PMID- 12209426
TI  - Arthroscopic posterior cruciate ligament repair.
AB  - PURPOSE: We present our technique of arthroscopic repair for femoral avulsion
      soft-tissue tears of the posterior cruciate ligament (PCL) and its results. TYPE
      OF STUDY: Case series, retrospective review. METHODS: We performed 13
      arthroscopic repairs of the PCL and reviewed them retrospectively. Follow-up was
      available for 11 (85%) patients. Nonabsorbable monofilament sutures were placed
      through the loose fibers of the ligament and tied over a bone bridge. Patients
      were evaluated using magnetic resonance imaging, comparative stress views, and
      according to the scoring systems of Lysholm and Gillquist and the International
      Knee Documentation Committee (IKDC). RESULTS: Mean follow-up was 51.4 months.
      IKDC scores revealed 4 (36.4%) patients with normal knee function, and 7 (63.6%)
      with nearly normal function. Average Lysholm and Gillquist score was 95.4 (90 to
      100). All athletes returned to the same or a higher level of competition.
      CONCLUSIONS: Arthroscopic repair of the PCL in patients with a femoral avulsion
      is effective in reducing postoperative instability and improving functional
      outcome.

PMID- 12209427
TI  - Arthroscopically assisted combined anterior and posterior cruciate ligament
      reconstruction in the multiple ligament injured knee: 2- to 10-year follow-up.
AB  - PURPOSE: This study presents the 2- to 10-year results of 35 arthroscopically
      assisted combined anterior cruciate ligament and posterior cruciate ligament
      (ACL/PCL) reconstructions evaluated preoperative and postoperatively using
      Lysholm, Tegner, and Hospital for Special Surgery knee ligament rating scales, KT
      1000 arthrometer testing, stress radiography, and physical examination. TYPE OF
      STUDY: Case series. METHODS: This study population included 26 men and 9 women
      with 19 acute and 16 chronic knee injuries. Ligament injuries included 19
      ACL/PCL/posterolateral instabilities, 9 ACL/PCL/medial cruciate ligament (MCL)
      instabilities, 6 ACL/PCL/posterolateral/MCL instabilities, and 1 ACL/PCL
      instability. All knees had grade III preoperative ACL/PCL laxity and were
      assessed preoperatively and postoperatively with arthrometer testing, 3 different
      knee ligament rating scales, stress radiography, and physical examination.
      Arthroscopically assisted combined ACL/PCL reconstructions were performed using
      the single-incision endoscopic ACL technique and the single femoral tunnel-single
      bundle transtibial tunnel PCL technique. PCLs were reconstructed with allograft
      Achilles tendon (in 26 cases), autograft bone-patellar tendon-bone (BPTB) (in 7
      cases), and autograft semitendinosus/gracilis (in 2 cases). ACLs were
      reconstructed with autograft BPTB (16 cases), allograft BPTB (12 cases), Achilles
      tendon allograft (6 cases), and autograft semitendinosus/gracilis (1 case). MCL
      injuries were treated with bracing or open reconstruction. Posterolateral
      instability was treated with biceps femoris tendon transfer, with or without
      primary repair, and posterolateral capsular shift procedures as indicated.
      RESULTS: Postoperative physical examination revealed normal posterior
      drawer/tibial step-off in 16 of 35 (46%) knees. Normal Lackman and pivot-shift
      test results were found in 33 of 35 (94%) knees. Posterolateral stability was
      restored to normal in 6 of 25 (24%) knees, and tighter than normal knee results
      were found in 19 of 25 (76%) knees evaluated with the external rotation thigh
      foot angle test. In this group, 30 degrees varus stress testing was normal in 22
      of 25 (88%) knees, and grade 1 laxity was found in 3 of 25 (12%) knees. 30
      degrees valgus stress testing was normal in 7 of 7 (100%) surgically treated MCL
      tears, and in 7 of 8 (87.5%) brace-treated knees. Postoperative KT-1000
      arthrometer testing mean side-to-side difference measurements were 2.7 mm (PCL
      screen), 2.6 mm (corrected posterior), and 1.0 mm (corrected anterior)
      measurements, a statistically significant improvement from preoperative status (P
      =.001). Postoperative stress radiographic side-to-side difference measurements
      measured at 90 degrees of knee flexion and 32 lb posteriorly directed proximal
      force were 0 to 3 mm in 11 of 21 (52.3%) knees, 4 to 5 mm in 5 of 21 (23.8%), and
      6 to 10 mm in 4 of 21 (19%) knees. Postoperative Lysholm, Tegner, and HSS knee
      ligament rating scale mean values were 91.2, 5.3, and 86.8, respectively, showing
      a statistically significant improvement from preoperative status (P =.001).
      CONCLUSIONS: Combined ACL/PCL instabilities can be successfully treated with
      arthroscopic reconstruction and the appropriate collateral ligament surgery.
      Statistically significant improvement is noted from the preoperative condition at
      2- to 10-year follow-up using objective parameters of knee ligament rating
      scales, arthrometer testing, stress radiography, and physical examination.
      Postoperatively, these knees are not normal, but they are functionally stable.
      Continuing technical improvements will probably improve future results.

PMID- 12209428
TI  - Quadruple hamstring anterior cruciate ligament reconstruction: a multicenter
      study.
AB  - PURPOSE: The use of blunt-threaded titanium interference screws for arthroscopic
      assisted fixation of a quadruple-strand hamstring anterior cruciate ligament
      (ACL) reconstruction has recently been reported. However, the pitfalls of the low
      medial portal technique, rehabilitation protocol, and long-term results have not.
      The purpose of this multicenter study was to prospectively evaluate this
      technique's application to ACL instability in symptomatic patients as well as to
      develop a standardized rehabilitation protocol. TYPE OF STUDY: Observation cohort
      study. METHODS: One hundred-twenty patients had quadruple hamstring ACL
      reconstructions, followed the study protocol, and were seen at 2 years follow-up.
      They were evaluated using Lysholm score, Lachman test, anterior drawer test,
      pivot-shift test, KT-1000, effusion assessment, and the Tegner Sports Activity
      Scale. RESULTS: The average Lysholm score improved 42 points; Lachman test,
      effusion assessment, anterior drawer test, KT-1000, and Tegner Sports Activity
      Scale scores all improved. Of 120 ACL reconstructions, 5 failed. Of these, 3
      failed from new late injury, 1 from technical error, and 1 from patient
      nonadherence to rehabilitation protocol. Some anterior knee pain was present in
      30% of patients, and 22% had at some time experienced hamstring pain that did not
      interfere with athletic activity. CONCLUSIONS: This multicenter study reports
      success with quadruple hamstring ACL reconstruction using the low medial portal
      technique. Specific pitfalls and a rehabilitation protocol are also discussed.
      Low medial portal position is critical in successful surgery. Variations in screw
      size to accommodate the variation in graft construct size are also recommended.

PMID- 12209429
TI  - The influences of biomechanical factors on cartilage regeneration after high
      tibial osteotomy for knees with medial compartment osteoarthritis: clinical and
      arthroscopic observations.
AB  - PURPOSE: A high tibial osteotomy (HTO) is often performed on knees with medial
      compartment osteoarthritis. However, in varus knees with medial compartment
      osteoarthritis, degeneration of the articular cartilage tends to progress due to
      medial deviation of the mechanical axis. This can result in eburnated bone. A
      widening of the medial joint space has been observed after HTO with a proper
      correction as a result of decreased stress on the load-bearing cartilage in the
      medial compartment. Researchers have reported obtaining a repair of the articular
      cartilage with both eburnation and clinical improvement using HTO in patients
      showing a medial deviation of the mechanical axis. However, which factors
      influence cartilage regeneration remain unclear. The purpose of this study was to
      quantitatively evaluate the influence of cartilage regeneration after a high
      tibial osteotomy for knees with medial compartment osteoarthritis. TYPE OF STUDY:
      Observational cohort study. METHODS: The study involved 58 knees in 47 patients.
      A modified Noyes classification was used for arthroscopic grading. The patients
      underwent a second look arthroscopic evaluation of the articular cartilage 18
      months after surgery. The articular cartilage was classified as no regenerative
      change (grade 1), white scattering with fibrocartilage (grade 2), partial
      coverage with fibrocartilage (grade 3), and even coverage with fibrocartilage
      (grade 4). The functional results were evaluated according to the Japanese
      Orthopedic Association score for osteoarthritic knees (JOA score), femorotibial
      angle (FTA), percentage of mechanical axis, and body mass index (BMI). RESULTS:
      Partial or even coverage with fibrocartilage (grade 3 and 4) was achieved on 55%
      of the femorotibial joint surfaces. A repair with white scattering with
      fibrocartilage (grade 2) was achieved in 34%, and 3 knees showed no regenerative
      change (grade 1). At follow up, significant differences were seen between grade 4
      and grade 1 in JOA score and percentage of mechanical axis. CONCLUSIONS: This
      study demonstrates the correlation between the visible improvement of the
      articular surface, the functional score, and the degree of correction obtained
      with a lateral closing wedge HTO.

PMID- 12209430
TI  - Articular cartilage defects in 1,000 knee arthroscopies.
AB  - PURPOSE: Focal chondral or osteochondral defects can be painful and disabling,
      have a poor capacity for repair, and may predispose patients for osteoarthritis.
      New surgical procedures that aim to reestablish hyaline cartilage have been
      introduced and the results seem promising. The purpose of this study is to
      provide reliable data on chondral and osteochondral defects in patients with
      symptomatic knees requiring arthroscopy and to calculate the prevalence of
      patients who might benefit from cartilage repair surgery. TYPE OF STUDY:
      Prospective study. METHODS: One thousand consecutive knee arthroscopies were
      included in this study. Immediately after each arthroscopy, the surgeon completed
      a questionnaire providing detailed information about the findings. Chondral and
      osteochondral lesions were classified in accordance with the system recommended
      by the International Cartilage Repair Society (ICRS). RESULTS: Chondral or
      osteochondral lesions (of any type) were found in 61% of the patients. Focal
      chondral or osteochondral defects were found in 19% of the patients. In these
      patients, 61% related their current knee problem to a previous trauma, and a
      concomitant meniscal or anterior cruciate ligament injury was found in 42% (n =
      81) and 26% (n = 50), respectively. The mean chondral or osteochondral total
      defect area was 2.1 cm(2) (range, 0.5 to 12; standard deviation [SD], 1.5). The
      main focal chondral or osteochondral defect was found on the medial femoral
      condyle in 58%, patella in 11%, lateral tibia in 11%, lateral femoral condyle in
      9%, trochlea in 6%, and medial tibia in 5%. It has been suggested that cartilage
      repair surgery may be most suitable in patients younger than 40 to 50 years old.
      A single, well-defined ICRS grade III or IV defect with an area of at least 1
      cm(2) in a patient younger than 40, 45, or 50 years accounted for 5.3%, 6.1%, and
      7.1% of all arthroscopies, respectively. CONCLUSIONS: Our study supports the
      contention that articular cartilage defects are common. It has the advantages of
      a prospective design and use of a new classification system recommended by the
      ICRS. This modern system focuses on objectively measurable parameters of the
      lesion's extent and not its surface appearance.

PMID- 12209431
TI  - Hypertrophy of the synovium in the anteromedial aspect of the knee joint
      following trauma: an unusual cause of knee pain.
AB  - PURPOSE: The purpose of this study was to describe the arthroscopic clinical
      findings and treatment in patients with pathologic hypertrophy of the synovium in
      the anteromedial joint compartment in conjunction with anteromedial knee pain.
      TYPE OF STUDY: Case series. METHODS: A group of 21 patients, ranging in age from
      11 to 68 years (mean, 29 years) with pathologic hypertrophic changes of the
      synovium in the anteromedial joint compartment were studied. Pathologic changes
      included inflammation, polyp-type appearances, or hypertrophic string forming a
      loop. The most significant clinical finding was pain in the anteromedial aspect
      of the knee joint. Of the 21 cases, 20 (95%) had a history of trauma to the
      involved knee. Assessments performed included Lysholm knee scores with a special
      emphasis on knee pain. The duration of symptoms ranged from 2 to 32 months (mean,
      13 months). Treatment consisted of an arthroscopic evaluation followed by
      debridement of the hypertrophic synovium using a laser, shaver, or thermal
      debrider. RESULTS: The mean follow-up was 5.1 years (1.2 to 10 years). Mean
      Lysholm score improved from 64.1 to 96.4 (P <.05). Specifically, the pain score
      improved from 4.3 to 23 (P <.05). All patients were free of pain within 3 weeks
      following arthroscopic debridement. Return to normal function, including sports,
      was achieved for all patients within 2 months. Arthroscopic evaluation revealed
      that 18 of 21 (86%) knees had mild chondral damage on the medial femoral condyle,
      grade I or II according to Outerbridge grading. CONCLUSIONS: Based on the
      clinical and arthroscopic findings, we concluded that pathologic hypertrophy of
      the synovium in the anteromedial joint compartment may result following trauma,
      causing mild chondromalacia changes in the medial femoral condyle and knee pain.
      Arthroscopic debridement of this pathologic tissue significantly improves
      symptoms.

PMID- 12209432
TI  - Osteoarthritis caused by an inverted acetabular labrum: radiographic diagnosis
      and arthroscopic treatment.
AB  - PURPOSE: An inverted labrum is an acknowledged but often elusive cause of
      osteoarthritis. The study goals were to define the characteristic radiographic
      features of secondary osteoarthritis of the hip due to an inverted labrum and
      report the results of arthroscopic treatment. TYPE OF STUDY: This is a case
      series study. METHODS: From 220 consecutive arthroscopic hip procedures, 9
      patients were identified who had had secondary osteoarthritis caused by an
      inverted labrum and who underwent a minimum 2 years follow-up. All were
      prospectively assessed with a modified Harris hip score. All patients underwent
      excision of a torn inverted labrum and chondroplasty. Three patients who had well
      circumscribed grade IV acetabular lesions also underwent microfracture of the
      subchondral bone. RESULTS: Characteristic anteroposterior radiographic features
      included isolated narrowing of the superolateral joint space. This narrowing
      caused a lateral convergence in the normally parallel lines created by the radius
      of curvature of the subchondral bone of the acetabulum and the convex surface of
      the femoral head. These 2 features created a false appearance of dysplasia
      (pseudodysplasia), because the center edge angle of Weiberg was normal in 6 cases
      (range, 24 degrees to 41 degrees; average, 29 degrees ) and was indicative of
      true dysplasia in only 3 cases (17 degrees ). The median preoperative score was
      51, and the postoperative hip score was 56. Only 4 patients showed significant
      improvement. The best results were in the group with microfracture; the average
      improvement in this group was 36. CONCLUSIONS: An inverted labrum is an
      occasionally encountered cause of osteoarthritis of the hip. The radiographic
      features seen with this disorder are quite characteristic and essentially
      pathognomonic. Recognizing these features in this population may help the
      physician avoid an unnecessarily extensive work-up for poorly explained hip pain.
      The 3 patients with microfracture responded well to the arthroscopic technique;
      otherwise the results of arthroscopic treatment were poor. The outcomes were no
      better than those previously reported for arthritis of all causes.

PMID- 12209433
TI  - The effect of continuous cryotherapy on glenohumeral joint and subacromial space
      temperatures in the postoperative shoulder.
AB  - PURPOSE: The objective of this investigation was to determine the effect of
      continuous cryotherapy on glenohumeral joint and subacromial space temperatures
      in the postoperative shoulder. TYPE OF STUDY: Prospective, randomized, and
      controlled clinical trial. METHODS: Twenty patients (10 cryotherapy, 10 controls)
      with a full-thickness rotator cuff repair were monitored with temperature sensors
      in the glenohumeral joint and subacromial space of the shoulder for 23
      postoperative hours. Statistical analysis (P <.05) was performed using the Mann
      Whitney rank-sum test. RESULTS: In comparing the cryotherapy and control groups,
      analysis of the glenohumeral joint and subacromial space temperatures revealed a
      statistical significance at 4, 8, and 23, and 4, 8, 16, and 20 postoperative
      hours, respectively. In addition, a trend toward a temperature-rising phase
      occurs from 4 to 12 hours and is followed by a trend toward a thermostatic phase
      from 12 to 23 hours during which temperatures remain relatively constant. The
      subacromial space was consistently cooler than the glenohumeral joint by an
      interval between 0.07 degrees C to 0.50 degrees C except at 23 hours
      postoperative where the glenohumeral joint was 0.05 degrees C cooler.
      CONCLUSIONS: Continuous cryotherapy causes a statistically significant reduction
      of both glenohumeral joint and subacromial space temperatures in the shoulder at
      variable times during the first 23 postoperative hours. Previous investigations
      have shown that minor elevations in intra-articular temperature can stimulate
      proteolytic enzyme activity, which has detrimental effects on articular
      cartilage. Previous research has also shown that cryotherapy is an effective
      nonpharmacological method of pain control. Yet the literature has assumed that
      the effects of cryotherapy are part of the basic analgesia mechanism because of a
      reduction in joint temperature. Our results affirm that reductions in
      glenohumeral joint and subacromial space temperatures in the postoperative
      shoulder do occur, leading to potential benefits of continuous cryotherapy as an
      effective mode of pain control in the postoperative care of patients.

PMID- 12209434
TI  - Bankart repair in traumatic anterior shoulder instability: open versus
      arthroscopic technique.
AB  - PURPOSE: The purpose of this study was to compare the results of open and
      arthroscopic Bankart repair using suture anchors in traumatic anterior
      glenohumeral instability. Variables measured were recurrence rate, range of
      motion, and return to preinjury activity. TYPE OF STUDY: Case control study.
      METHODS: Eighty-nine shoulders in 88 patients with traumatic unilateral anterior
      shoulder instability were evaluated using Rowe and University of California Los
      Angeles scores, recurrence, return to activity, and range of motion by an
      independent examiner at an average of 39 months after either an arthroscopic or
      open Bankart repair using suture anchors. The arthroscopic technique included a
      minimum of 3 anchors in most patients and a routine incorporation of capsular
      plication and proximal shift. Of the 89 shoulders, 30 shoulders (30 patients)
      underwent open Bankart repair and 59 shoulders (58 patients) underwent
      arthroscopic Bankart repair. RESULTS: Twenty-six shoulders (86.6%) in the open
      repair group showed excellent or good results, and 54 (91.5%) shoulders in the
      arthroscopic repair group showed excellent or good results. The arthroscopic
      group revealed slightly higher scores in the Rowe (P =.041) and UCLA scores (P
      =.026). Two patients (6.7%) in the open repair group and 2 (3.4%) in the
      arthroscopic repair group had experienced at least 1 episode of redislocation
      after the surgery. One patient (3.3%) in the open repair group and 4 (6.8%) in
      the arthroscopic repair group demonstrated mild apprehension. The overall
      residual instability was 10% in the open repair group and 10.2% in the
      arthroscopic repair group. There were no significant differences in the loss of
      external rotation and return to prior activity between the 2 groups (P >.05).
      Residual instability occurred more frequently in patients with fewer anchors.
      CONCLUSIONS: Arthroscopic suture anchor capsulorraphy showed similar results to
      the open Bankart procedure.

PMID- 12209435
TI  - Arthroscopic approach to acute bony Bankart lesion.
AB  - PURPOSE: To report on an arthroscopic approach to a bony Bankart lesion that uses
      a modified Bankart technique to fix the avulsed bone fragment to the healthy
      glenoid. TYPE OF STUDY: Case series study. METHODS: Of 250 patients who received
      surgical treatment for shoulder dislocation at our unit, 25 sport-practicing
      patients with acute traumatic dislocation of the shoulder and anterior glenoid
      rim fracture were included in this study. Inclusion criteria were bony Bankart
      lesions less than 3 months old and involving less than 25% of the glenoid,
      absence of associated lesions, and follow-up longer than 2 years. Arthroscopic
      procedures were performed using a modified Bankart technique to fix the avulsed
      bone fragment to the healthy glenoid rim using suture anchors. A modified Rowe
      score was devised for evaluating range of motion outcomes. RESULTS: Shoulder
      function and stability were restored in 23 patients (92%) by 2 years after
      surgery. There was no recurrence of instability. Range of motion was minimally
      reduced. All patients resumed sports activities: 23 (92%) at the same level of
      performance as before surgery and 2 (8%) at a lower level because of 20 degrees
      loss of external rotation. CONCLUSIONS: This arthroscopic technique seems to
      offer an optimal method for evaluating and treating isolated acute bony Bankart
      lesions involving less than 25% of the glenoid.

PMID- 12209436
TI  - Shoulder proprioception and function following thermal capsulorraphy.
AB  - PURPOSE: Because monopolar radiofrequency energy has a denaturing effect on the
      glenohumeral joint capsule during thermal capsulorraphy, we hypothesized that
      thermal treatment would have a deleterious effect on the mechanoreceptors present
      within the capsule, thereby affecting proprioception and function. The purpose of
      this study was to evaluate proprioception and function following thermal
      capsulorraphy. TYPE OF STUDY: Case series. METHODS: Twenty subjects (13 male, 7
      female) diagnosed with unilateral anterior, anteroinferior, or multidirectional
      glenohumeral instability with no significant concomitant pathologies, were
      treated with monopolar radiofrequency thermal capsulorraphy by one surgeon.
      Capsular redundancy was the primary diagnosis in all subjects. Subjects were
      bilaterally tested retrospectively 6 to 24 months (11.90 +/- 5.65 months)
      following surgery. Each subject's ability to actively reproduce joint positions
      (ARJP) and reproduce paths of motion (PMR) was measured with an electromagnetic
      motion analysis system. Both passive reproduction of joint positions (PRJP) and
      threshold to detect passive motion (TTDPM) were measured using a proprioception
      testing device. Function was quantified with the Shoulder Rating Questionnaire
      (SRQ). Proprioception data were analyzed with separate repeated measures ANOVA (P
      <.05). RESULTS: Statistical analysis revealed a significant ARJP difference
      between the involved and uninvolved limb (P =.005) indicating that reproduction
      error was less with the involved limb compared to the uninvolved limb. No
      significant interactions were present for TTDPM, PRJP, or PMR. The SRQ indicates
      that the subjects returned to near normal function (91.86/100 +/- 5.38 points) at
      the time of testing. CONCLUSIONS: The results from this study do not support our
      hypothesis of proprioception and functional deficits following thermal treatment.
      Normalized proprioception following thermal capsulorraphy may have resulted from
      the healing effects of thermal treated ligament, as reported in the literature,
      as well as facilitation of other mechanoreceptors present in adjacent tissue
      about the shoulder joint during rehabilitation. The results of this study
      indicate that no appreciative deleterious effects exist with proprioception and
      function following treatment of shoulder instability with thermal capsulorraphy.

PMID- 12209437
TI  - Thermal chondroplasty with bipolar and monopolar radiofrequency energy: effect of
      treatment time on chondrocyte death and surface contouring.
AB  - PURPOSE: The purpose of this study was to evaluate chondrocyte viability and
      surface contouring of articular cartilage using confocal laser microscopy (CLM)
      and scanning electron microscopy (SEM), respectively, during different treatment
      time intervals with monopolar and bipolar radiofrequency energy (RFE). TYPE OF
      STUDY: In vitro analysis using chondromalacic human cartilage. METHODS: Forty-two
      fresh osteochondral sections from patients undergoing partial or total knee
      arthroplasties were used to complete this study. Each of 36 sections was divided
      into 2 distinct 1-cm(2) regions that were treated with either bipolar or
      monopolar RFE. Six sections were maintained as untreated controls. Six RF
      treatment time intervals were evaluated: 5, 10, 15, 20, 30, and 40 seconds (6
      specimens per time interval per group). After treatment, each specimen was
      processed for CLM and SEM. RESULTS: CLM demonstrated that the depth of
      chondrocyte death in the monopolar RFE treatment group was significantly less
      than the bipolar group at each of the same time intervals (P <.05). SEM showed
      that each RFE device began to contour and smooth the articular surface after 15
      seconds of treatment. CONCLUSIONS: When applying thermal chondroplasty, a broad
      treatment time range could result in variable degrees of cartilage smoothness and
      significant chondrocyte death.

PMID- 12209438
TI  - The role of arthroscopic synovectomy in the management of hemarthrosis in
      hemophilia patients: financial perspectives.
AB  - PURPOSE: The purpose of this study was to determine the financial efficacy of
      arthroscopic synovectomy in hemophilia patients with recurrent hemarthroses. TYPE
      OF STUDY: Cost-benefit analysis. METHODS: A retrospective chart review from 1993
      through 1999 yielded 11 cases of arthroscopic synovectomies performed for
      recurrent hemarthroses at the University of Michigan. There were 7 ankle
      arthroscopies, 3 elbow arthroscopies, and 1 knee arthroscopy. The average age of
      the patients was 8 years (range, 4-13 years). All had the severe form of
      hemophilia A. The average follow-up was 41 months (range, 9-75 months). The
      preoperative costs were determined by multiplying the number of preoperative
      bleeds by the dollar amount of the replacement therapy used to treat the
      hemarthroses. The surgical costs included the surgery itself as well as the
      hospital stay and the dollar amount of the replacement therapy used in the
      perioperative period. The total postoperative costs included the surgical costs
      and the dollar amount of any replacement therapy used to treat any postoperative
      hemarthroses. RESULTS: The financial benefit of arthroscopic synovectomy was
      found to be statistically significant when average preoperative cost per month
      ($7,500) was compared with the average postoperative cost per month ($900), P
      =.028. Arthroscopic synovectomy was again found to be financially beneficial when
      the average total preoperative cost ($88,000) was compared with the average total
      postoperative cost ($24,000), P =.028. The average number of hemarthroses
      preoperatively was 71 and the average postoperatively was 7, which was
      statistically significant (P =.028). CONCLUSIONS: In this small series of
      patients with intermediate follow-up, arthroscopic synovectomy was found to be
      cost effective in the treatment of patients with recurrent hemarthroses.

PMID- 12209439
TI  - Arthroscopic proficiency: a survey of orthopaedic sports medicine fellowship
      directors and orthopaedic surgery department chairs.
AB  - PURPOSE: The goal of this study was to evaluate the opinion of sports medicine
      fellowship directors and orthopaedic surgery department chairpersons on how many
      repetitions the average resident needs to become proficient in several common
      arthroscopic procedures. TYPE OF STUDY: A cross-sectional study. METHODS: A
      questionnaire was mailed to all fellowship directors on a list maintained by the
      American Academy of Orthopaedic Surgeons and to all department chairpersons on a
      list maintained by the American Medical Association. Respondents were asked to
      estimate the number of operations needed for a trainee to reach minimal
      proficiency (able to perform procedure skin-to-skin with supervision) and
      proficiency (capable of performing procedure without supervision) for 5 common
      arthroscopic procedures: diagnostic knee scope, partial medial meniscectomy,
      anterior cruciate ligament (ACL) reconstruction, diagnostic shoulder scope, and
      subacromial decompression. RESULTS: A total of 164 of 230 (71%) people responded
      to the questionnaire. Department chairpersons who did not perform arthroscopy
      consistently estimated two thirds the number of operations that department
      chairpersons who did perform arthroscopy and nearly half the number of operations
      estimated by fellowship directors. Chairpersons who did perform arthroscopy had
      responses more similar to fellowship directors than to department heads who did
      not perform arthroscopy. CONCLUSIONS: These results indicate that, in the opinion
      of physicians involved in the education of residents and fellows, it may take a
      substantial number of repetitions to become proficient in arthroscopy. Physicians
      who perform little or no arthroscopy themselves may underestimate its difficulty.
      Interestingly, there was substantial variability in the number of repetitions
      estimated to achieve proficiency in all procedures. The results of this study may
      be helpful in designing arthroscopic training programs for orthopaedic residents
      or sports medicine fellows; however, the wide variability in opinions may
      indicate difficulty in reaching a consensus.

PMID- 12209440
TI  - Arthroscopic removal of an osteoid osteoma of the shoulder.
AB  - Two cases of arthroscopic retrieval of intra-articular shoulder pathology are
      presented. With this technique, areas that are often difficult to expose in an
      open fashion and those previously deemed inaccessible arthroscopically are
      localized readily. In the setting of intra-articular pathology, thought should be
      given to the possibility of arthroscopic retrieval or excision before proceeding
      with open surgery.

PMID- 12209441
TI  - Chronic lateral knee instability treated with a high tibial osteotomy.
AB  - Published studies have recommended correction of osseous alignment in patients
      with chronic deficiencies of multiple knee ligaments and varus angulation.
      However, similar treatment for isolated chronic lateral collateral ligament
      deficiency has not been reported. We report such a case treated successfully with
      a medial high tibial osteotomy using a dynamic external fixator.

PMID- 12209442
TI  - A safe, easy, and inexpensive technique for patient positioning in shoulder
      surgery.
AB  - We describe a technique that uses the Vac Pac (Olympic Medical, Seattle, WA) for
      patient positioning in shoulder surgery. This technique is well-liked by
      anesthesiologists, nurses, and operating room staff because of its ease and
      simplicity. If careful attention is given to detail during positioning, problems
      with encroachment on the operative field can be avoided. We believe this
      technique allows for safe and effective patient positioning for shoulder surgery
      using the readily available and inexpensive Vac Pac.

PMID- 12209443
TI  - The double-twist knot: a new arthroscopic sliding knot.
AB  - A safe and easy-to-tie sliding knot is necessary for arthroscopic repair of
      rotator cuff tears and glenoid labrum lesions. We describe the double-twist knot
      (DTK) technique, having tested the knot's tensile strength and compared it with
      other commonly used arthroscopic knots. The DTK is a modified Lark's head knot
      that can be tied only on a double suture. A No. 2 braided polyester suture was
      used to test the DKT against the Tennessee slider knot and Snyder's knot by means
      of a material testing system. Results showed a statistically significant (P
      <.001) higher tensile strength with the DTK than with the other 2 knots. The
      rationale for using a stitch with a double suture is to double the tensile
      strength while using the same number of surgical steps and operating time as with
      single-suture stitches.

PMID- 12209444
TI  - DNA binding induces conformational transition within human DNA topoisomerase I in
      solution.
AB  - We employed Raman and circular dichroism (CD) spectroscopy to probe the molecular
      structure of 68-kDa recombinant human DNA topoisomerase I (TopoI) in solution, in
      a complex with a 16-bp DNA fragment containing a camptothecin-enhanced TopoI
      cleavage site, and in a ternary complex with this oligonucleotide and topotecan.
      Raman spectroscopy reveals a TopoI secondary structure transition and significant
      changes in the hydrogen bonding of the tyrosine residues induced by the DNA
      binding. CD spectroscopy confirms the Raman data and identifies a DNA-induced
      (>7%) decrease of the TopoI alpha helix accompanied by at least a 6% increase of
      the beta structure. The Raman DNA molecular signatures demonstrated a bandshift
      that is expected for a net change in the environment of guanine C6 [double bond]
      O groups from pairing to solvent exposure. The formation of a ternary cleavage
      complex with TopoI, DNA, and topotecan as probed by CD spectroscopy reveals
      neither additional modifications of the TopoI secondary structure nor of the
      oligonucleotide structure, compared to the TopoI-oligonucleotide complex.

PMID- 12209445
TI  - Detailed account of confounding factors in interpretation of FTIR spectra of
      exfoliated cervical cells.
AB  - The confounding variables that can potentially lead to a misinterpretation of
      FTIR spectroscopy of exfoliated cervical cells is described. A detailed account
      of the spectral effects of the following variables in FTIR spectroscopic
      screening of exfoliated cervical cells is presented: polymorphs; Cell
      degradation; and impurities such as endocervical columnar cells, metaplastic
      cells, cervical mucus, red cells, and debris. The interpretation of the spectra
      of exfoliated cervical cells must be done with subtraction analysis, which
      includes these factors. This is essential to prevent unacceptable false-positive
      rates. The above techniques are subsequently applied to two clinic populations: a
      dysplasia clinic in follow-up patients with negative cytology and two general
      gynecology clinics with patients with negative cytology. In the dysplasia clinic
      group 250 sequential patients with negative smears were tested. Thirty had false
      positive smears as defined by the IR spectroscopy using the above methodology.
      Twenty of those patients subsequently had one follow-up and six had a positive
      abnormal smear. In the community clinic group 656 sequential patients were
      examined who had negative smears, of which 27 had false-positive FTIR spectra.

PMID- 12209446
TI  - Effects of terbium and pH on structure of anticoagulation factor II from
      Agkistrodon acutus venom probed by fluorescent spectroscopy and equilibrium
      dialysis.
AB  - Anticoagulation factor II (ACF II) isolated from the venom of Agkistrodon acutus
      is an activated coagulation factor X-binding protein with marked anticoagulant
      activity. Present studies show that the pH has a marked effect on the
      fluorescence intensity of holo-ACF II; however, no appreciable shift of the
      emission maximum of holo-ACF II was observed in the pH range of 3-10. It was
      deduced from a relatively weak fluorescence emission of holo-ACF II at a neutral
      pH (6-7) that native holo-ACF II assumes a compactly folded structure in which
      the most interior Trp residues and quenchers are adjacent. Terbium ions can
      completely replace both Ca2+ ions in holo-ACF II as determined by equilibrium
      dialysis. Two Tb3+-binding sites with different apparent Tb3+ association
      constant values, (2.1 +/- 0.2) and (1.0 +/- 0.1) x 10(7) M(-1), were identified
      through Tb3+ fluorescence titration. In addition, it was confirmed from the
      titration of holo-ACF II and Tb3+-ACF II with N-bromosuccinimide (NBS) that only
      interior Trp residues are involved in the energy transfer to Tb3+ ions and all
      accessible Trp residues located in the surface of holo-ACF II have a similar
      affinity to NBS while those located in the surface of Tb3+-ACF II have two
      different kinds of affinity to NBS, which suggests a conformational change of
      holo-ACF II on the substitution of Tb3+ for Ca2+.

PMID- 12209447
TI  - Two-dimensional near-IR correlation spectroscopy study of molten globule-like
      state of ovalbumin in acidic pH region: simultaneous changes in hydration and
      secondary structure.
AB  - The molten globule-like states of ovalbumin (OVA) in acid aqueous solutions are
      investigated by generalized two-dimensional (2D) Fourier transform near-IR (FT
      NIR) correlation spectroscopy. This new method allows us to explore the changes
      in hydration and the secondary structure simultaneously. FT-NIR spectra are
      measured for OVA aqueous solutions with concentrations of 1, 2, 3, 4, and 5 wt %
      over a pH range of 2.4-5.4. Concentration-perturbed 2D correlation spectra are
      calculated for the spectra in the 4850-4200 and 7500-5350 cm(-1) regions at
      different pH values. The 2D NIR synchronous spectrum in the 4850-4200 cm(-1)
      region shows a significant change upon going from pH 5.4 to 3.6. An autopeak at
      4265 cm(-1) that is due to a combination of a symmetric CH(2) stretching mode and
      a CH(2) bending mode of side chains seen at pH 5.0 disappears completely in the
      synchronous spectrum at pH 3.6. This suggests that some amino acid residues of
      OVA are subjected to microenvironmental changes with decreasing pH. More
      remarkable changes are observed in the synchronous spectra at pHs below 2.8. A
      band near 4600 cm(-1) arising from a combination of amide B and amide II modes
      (amide B/II) shifts downward with considerable broadening between pH 3.0 and 2.4,
      suggesting that the strength of the hydrogen bonds of amide groups of OVA changes
      significantly. The synchronous and asynchronous spectra in the 4850-4200 cm(-1)
      region show that the intensities of the bands attributable to amide groups and
      side chains of OVA and that of the band near 4800 cm(-1) arising from water
      change in phase with the increase in the concentration above pH 2.8, but they
      vary out of phase below pH 2.8. The 2D synchronous map in the 7500-5350 cm(-1)
      region also shows marked changes upon going from pH 2.8 to 2.6. A broad autopeak
      at around 6950 cm(-1) assigned to free water and bound water with weak hydrogen
      bonds becomes very weak in the synchronous spectrum at pH 2.6, while broad
      autopeaks around 6450 cm(-1) suddenly appear that are due to bound water with
      several hydrogen bonds and the first overtone of an NH stretching mode of the
      amide groups of OVA. Therefore, it is very likely that protein hydration and the
      hydrogen bonds of amide groups change simultaneously in a narrow pH region of 2.8
      2.6. It is probably that below pH 2.6 the protein assumes a molten globule-like
      state in which the whole molecule is very flexible, and side chains (but not the
      backbone chain) fluctuate significantly.

PMID- 12209448
TI  - FTIR spectroscopic method for detection of cells infected with herpes viruses.
AB  - Microscopic FTIR spectroscopy was used to investigate the spectral differences
      between normal cells in culture and cells infected with various members of the
      herpes family of viruses [Herpes simplex (HSV) and Varicella zoster (VZV)]. The
      main objective of this study is to evaluate the possibility of developing
      microscopic FTIR spectroscopy as a sensitive assay for the detection of herpetic
      infections at their early stages. The advantage of this method over conventional
      FTIR spectroscopy is that it facilitates inspection of restricted regions of
      tissue. Our results showed significant and consistent differences between all
      normal and HSV or VZV infected cells that were tested. Detectable and significant
      spectral differences between normal and infected cells are seen as early as 24 h
      postinfection, but the damage of the cells (cytopathic effect), caused by the
      infecting virus, can be seen by optical microscope observations at only 3 days
      postinfection. An impressive increase in the levels of vital cellular metabolites
      was seen in the herpes virus infected cells compared to normal cells. It seems
      that this spectral behavior is unique for infection with herpes viruses, because
      when these cells were infected with other viruses from different families like
      retroviruses, a considerable decrease in the levels of vital cellular metabolites
      was seen in infected cells compared to normal cells. Cluster analysis performed
      on FTIR mass chromatography yielded 100% accuracy in classifying control
      uninfected and VZV or HSV infected cells. Our data strongly support the
      possibility of developing FTIR microscopy as a diagnostic method for early
      detection of herpetic infections.

PMID- 12209449
TI  - Anomalously high cooperativity of oligodeoxycytidylic acid for luminescence
      resonance energy transfer to lanthanide ions.
AB  - The luminescence of terbium(III) and europium(III) through luminescence resonance
      energy transfer from mononucleotides and oligodeoxynucleotides is examined. Among
      mononucleotides, dGMP gives the strongest luminescence of terbium(III), while
      dTMP and dCMP yield a luminescence intensity of europium(III) that is larger than
      the other two cases. In the homodeoxydecamers, decadeoxycytidylic acid (dC10)
      produces the highest intensity for both metals. The anomalously large
      cooperativity of dC10 is explained by the easiness of deformation of the helical
      structure to bind lanthanide ions, and a circular dichroism study supports this
      explanation.

PMID- 12209450
TI  - Effect of biogenic amines on oxidation of farmorubicin by Fenton-like reagents.
AB  - The aim of this study was to investigate the effect of dopa and catecholamines on
      the generation of oxygen active species during oxidation of farmorubicin by
      "Fenton-like" reagents using chemiluminescent and spectrophotometric techniques.
      The tested catechols were found to reduce the light emission accompanying
      oxidation of farmorubicin by Co(II) + H2O2 and Cu(II) + H2O2 mixtures. The
      quenching effect was followed by their rapid oxidation to aminochromes possessing
      toxic activities.

PMID- 12209451
TI  - Vibrational, 1H-NMR spectroscopic, and thermal characterization of gladiolus root
      exudates in relation to Fusarium oxysporum f. sp. gladioli resistance.
AB  - Fourier transform Raman (FT Raman) and IR (FTIR) and (1)H-NMR spectroscopies
      coupled with differential scanning calorimetry (DSC) were applied to the
      characterization of root exudates from two cultivars of gladiolus (Spic Span and
      White Prosperity) with different degrees of resistance and susceptibility to
      Fusarium oxysporum gladioli, the main pathogen of gladiolus. This work was aimed
      at correlating the composition of root exudates with the varietal resistance to
      the pathogen. Spectroscopic analysis showed that White Prosperity root exudate
      differs from Spic Span root exudate by a higher relative amount of the aromatic
      phenolic and sugarlike components and a lower relative amount of carbonylic and
      aliphatic compounds. DSC analysis confirmed the spectroscopic results and showed
      that White Prosperity root exudate is characterized by an aromatic component that
      is present in a higher amount than in the Spic Span root exudate. The results are
      discussed in relation to the spore germination tests showing that White
      Prosperity, which is characterized by a remarkable resistance toward F. oxysporum
      gladioli, exudes substances having a negative influence on microconidial
      germination of the pathogen; root exudates from Spic Span, one of the most
      susceptible cultivars to F. oxysporum gladioli, proved to have no effect. White
      Prosperity's ability to inhibit conidial germination of F. oxysporum gladioli can
      be mainly related to the presence of a higher relative amount of aromatic
      phenolic compounds.

PMID- 12209452
TI  - Ab initio Hartree-Fock/6-31G** calculation on 9-beta-D-arabinofuranosyladenine-5'
      monophosphate molecule: application to the analysis of its IR and Raman spectra.
AB  - 9-beta-D-arabinofuranosyaldenine-5'-monophosphate (5'-ara-AMP) is an
      arabinonucleotide that has antiviral and antitumor activity. The accurate
      knowledge of the nature of its vibrational modes is a valuable step for the
      forthcoming elucidation of drug-nucleotide and drug-enzyme interactions. The FTIR
      and FT Raman spectra (4000-30 cm(-1)) of 5'ara-AMP and two deuterated derivatives
      ara-AMP-d(C8) (deuteration in C8) and ara-AMP-d7 (deuteration in C8, amino and
      hydroxyl groups) are reported. Theoretical vibrational calculations were
      performed using the Hartree-Fock/6-31G** method. An assignment of the observed
      spectra is proposed considering the scaled potential energy distribution of the
      vibrational modes of the 5'ara-AMP molecule and the observed band shifts by
      deuteration. The scaled ab initio frequencies are in good agreement with the
      experimental data (<3 cm(-1) SD).

PMID- 12209453
TI  - Two-dimensional correlation spectroscopy and principal component analysis studies
      of temperature-dependent IR spectra of cotton-cellulose.
AB  - The FTIR spectra were measured for raw Uplands Sicala-V2 cotton fibers over a
      temperature range of 40-325 degrees C to explore the temperature-dependent
      changes in the hydrogen bonds of cellulose. These cotton-cellulose spectra
      exhibited complicated patterns in the 3800-2800 cm(-1) region and thus were
      analyzed by both the exploratory principal component analysis (PCA) and two
      dimensional (2-D) correlation spectroscopy methods. The exploratory PCA showed
      that the spectra separate into two groups on the basis of thermal degradation of
      the cotton-cellulose and the consequent breakage of intersheet H-bonds present in
      its structure. Frequency variables, which strongly contributed to each principal
      component highlighted in its loadings plot, were linked to the frequencies
      assigned to vibrations of the OH groups involved in different kinds of H-bonds,
      as well as to vibrations of the CH groups. Deeper insights into reorganization of
      the temperature-dependent hydrogen bonding were obtained by 2-D correlation
      spectroscopy. Synchronous and asynchronous spectra were analyzed in the
      temperature ranges of 40 to 150 and 250 to 320 degrees C, the ranges indicated by
      PCA. Detailed band assignments of the OH stretching region and changes in the
      patterns of the hydrogen bonding network of the cotton-cellulose were proposed
      with the aid of the 2-D correlation spectroscopy analysis. Below 150 degrees C,
      distinctly different bands assigned to the less stable Ialpha and the more stable
      Ibeta interchain H-bonds O-6-H-6...O-3' were observed at about 3230 and 3270 cm(
      1), respectively. Evaporation of water entrapped in the cellulose network was
      examined by means of the band at about 3610 cm(-1). The cooperativity of hydrogen
      bonds, which play a key role in the cellulose conformation, was monitored by
      frequencies assigned to intrachain H-bonds. It was possible to separate the
      frequencies assigned to the O-2-H-2...O-6 and O-3-H-3...O-5 intrachain H-bonds
      into two separate ranges, the spread of which was controlled by the cooperativity
      effect. The temperature dependence of the asynchronous spectra indicated that the
      less stable O-3-H-3...O-5 bonds gave rise to an absorption extending from 3300 to
      3384 cm(-1), while the more stable O-2-H-2...O-6 bonds were characterized by the
      absorption between 3400 and 3470 cm(-1). The final breaking of the inter- and
      intrachain H-bonds, which occurs at the higher temperatures, was monitored by the
      asynchronous peaks at 3533 and 3590 cm(-1), respectively. On the basis of both
      the exploratory PCA and 2-D correlation spectroscopy investigations, it was
      possible to extract well-defined wavenumber ranges assigned to different kinds of
      intra- and interchain hydrogen bonds, as well as to the free OH groups of the
      cotton-cellulose.

PMID- 12209454
TI  - Surface enhanced IR absorption of nucleic acids from tumor cells: FTIR
      reflectance study.
AB  - The data on surface enhanced IR absorption (SEIRA) of nucleic acids deposited on
      a metal substrate were obtained using FTIR in reflectance mode. A 200-400 A thick
      gold film on a glass plate was the metal substrate. The approximate enhancement
      factors of the SEIRA for different vibrations of nucleic acids in our
      experimental conditions were 3-5. The roughness of the Au surface was about 50 A.
      Application of this method to nucleic acids isolated from tumor cells revealed
      some possible peculiarities of their structural organization, namely, the
      appearance of unusual sugar and base conformations, modification of the phosphate
      backbone, redistribution of the H-bond net, and so forth. This method enhanced a
      set of the bands, which is impossible to observe in conventional IR geometry. The
      SEIRA spectra of the RNA from tumor cells showed more sensitivity to the grade of
      tumor malignancy than the spectra of the DNA. After application of the anticancer
      drug doxorubicin to sensitive and resistant strains, the DNA isolated from these
      strains had different spectral features, especially in the region of the
      phosphate I and II bands. As induced by anticancer drugs, the conformational
      changes in the DNA from resistant and sensitive cancer strains could be
      characterized with different levels of structure disordering.

PMID- 12209455
TI  - Study of high molecular weight wheat glutenin subunit 1Dx5 by 13C and 1H solid
      state NMR spectroscopy. I. Role of covalent crosslinking.
AB  - This work describes a carbon and proton solid-state NMR study of the hydration of
      a high molecular weight wheat glutenin subunit, 1Dx5. The effect of the presence
      of disulfide bonds on the hydration behavior of the subunit is investigated by a
      comparison of the unalkylated and alkylated forms of the protein. Hydration
      induces partial plasticization of the protein so that some segments become more
      mobile than others. The 13C cross-polarization and magic-angle spinning (MAS)
      spectra of the samples in the dry state and at two hydration levels
      (approximately 40 and approximately 65% D2O) were used to monitor the protein
      fraction resisting plasticization (trains). Conversely, 13C single pulse
      excitation and 1H-MAS experiments were used to gain information on the more
      plasticized segments (loops). The molecular motion of the two protein dynamic
      populations was further characterized by 13C T1 and 1H T(1rho), T2, and T1
      relaxation times. The results suggest that hydration leads to the formation of a
      network held by a cooperative action of hydrogen bonded glutamines and some
      hydrophobic interactions. The looser protein segments are suggested to be glycine
      and glutamine-rich segments. The primary structure is therefore expected to
      significantly determine the proportion of trains and loops in the network. The
      presence of disulfide bonds was observed to promote easier plasticization of the
      protein and the formation of a more mobile network, probably involving a higher
      number of loops and/or larger loops.

PMID- 12209457
TI  - Circular dichroism spectra of DNA quadruplexes [d(G(5)T(5))](4) as formed with
      G(4) and T(4) tetrads and [d(G(5)T(5)). d(A(5)C(5))]2 as formed with Watson-Crick
      like (G-C)(2) and (T-A)(2) tetrads.
AB  - We utilize electrophoresis and find that a thermally treated equimolar mixture of
      the oligonucleotide d(G(5)T(5)) and its complementary oligonucleotide d(A(5)C(5))
      exhibits either two bands or a single band in one lane, depending on the
      conditions of the incubation solutions. The thermally treated d(G(5)T(5))
      solution loaded in a different lane exhibits a single band of the parallel
      quadruplex [d(G(5)T(5))](4), which is composed of homocyclic hydrogen-bonded G(4)
      and T(4) tetrads previously proposed. For the thermally treated equimolar mixture
      of d(G(5)T(5)) and d(A(5)C(5)), the fast band is assigned to a Watson-Crick
      d(G(5)T(5)). d(A(5)C(5)) duplex, so that the slow band with the same low mobility
      as that of [d(G(5)T(5))](4) may be assigned to either [d(G(5)T(5))](4) itself or
      a [d(G(5)T(5)). d(A(5)C(5))](2) quadruplex. If the latter compound is true, this
      may be the antiparallel quadruplex composed of the heterocyclic hydrogen-bonded G
      C-G-C and T-A-T-A tetrads proposed previously. After removing these three bands
      for the duplex and two kinds of hypothetical quadruplexes, we electrophoretically
      elute the corresponding compounds in the same electrophoresis buffer using an
      electroeluter. The eluted compounds are ascertained to be stable by
      electrophoresis. The circular dichroism (CD) and UV absorption spectra measured
      for the three isolated compounds are found to be clearly different. For the
      electrophoretic elution of the hypothetical [d(G(5)T(5))](4) quadruplex, the
      result of the molecularity of n = 4 obtained from the CD melting curve analysis
      provides further support for the formation of the parallel [d(G(5)T(5))](4)
      quadruplex already proposed. For the thermally treated equimolar mixture of
      d(G(5)T(5)) and d(C(5)A(5)), the fast band with a molecularity of n = 2
      corresponds to the Watson-Crick duplex, d(G(5)T(5)). d(A(5)C(5)). The slow band
      with a molecularity of n = 4 indicates the antiparallel quadruplex [d(G(5)T(5)).
      d(A(5)C(5))](2), whose observed CD and UV spectra are different from those of
      [d(G(5)T(5))](4). By electrophoresis, after reannealing the eluted compound
      [d(G(5)T(5)). d(A(5)C(5))](2), a distinct photograph showing the band splitting
      of this quadruplex band into the lower duplex and upper quadruplex bands is not
      possible; but by a transilluminator, we occasionally observe this band splitting
      with the naked eye. The linear response polarizability tensor calculations for
      the thus determined structures of the [d(G(5)T(5))](4) quadruplex, the McGavin
      like [d(G(5)T(5)). d(A(5)C(5))](2) quadruplex, and the Watson-Crick d(G(5)T(5)).
      d(A(5)C(5)) duplex are found to qualitatively predict the observed CD and UV
      spectra.

PMID- 12209456
TI  - Hydration of biological molecules: lipids versus nucleic acids.
AB  - We used FTIR spectroscopy to comparatively study the hydration of films prepared
      from nucleic acids (DNA and double-stranded RNA) and lipids (phosphatidylcholines
      and phosphatidylethanolamines chosen as the most abundant ones) at room
      temperature by varying the ambient relative humidity in terms of solvent-induced
      structural changes. The nucleic acids and phospholipids both display examples of
      polymorphism on the one hand and structural conservatism on the other; even
      closely related representatives behave differently in this respect. DNA undergoes
      a hydration-driven A-B conformational transition, but RNA maintains an A-like
      structure independently of the water activity. Similarly, a main transition
      between the solid and liquid-crystalline phases can be induced lyotropically in
      certain phosphatidylcholines, while their phosphatidylethanolamine counterparts
      do not exhibit chain melting under the same conditions. A principal difference
      concerning the structural changes that occur in the studied biomolecules is given
      by the relevant water-substrate stoichiometries. These are rather high in DNA and
      often low in phospholipids, suggesting different mechanisms of action of the
      hydration water that appears to induce structural changes on global- and local
      mode levels, respectively.

PMID- 12209458
TI  - Fourier transform IR and Fourier transform Raman spectroscopy studies of
      metallothionein-III: amide I band assignments and secondary structural comparison
      with metallothioneins-I and -II.
AB  - The secondary structures of porcine brain Cu(4)Zn(3)-metallothionein (MT)-III and
      Cd(5)Zn(2)MT-I, Cd(5)Zn(2)MT-II, and Zn(7)MT-I from rabbit livers in the solid
      state are investigated by Fourier transform IR spectroscopy (FTIR) and Fourier
      transform Raman spectroscopy (FT-Raman). The Cu(4)Zn(3)MT-III contains 26-28%
      beta-turns and half-turns, 13-14% 3(10)-helices, 47-49% random coils, and 11-12%
      beta-extended chains. The structural comparison of porcine brain Cu(4)Zn(3)MT-III
      with rabbit liver Cd(5)Zn(2)MT-I (II) and Zn(7)MT-I shows that the contents of
      the random coil structure are obviously increased. The results indicate that the
      insert of an acidic hexapeptide in the alpha domain of Cu(4)Zn(3)MT-III possibly
      forms an alpha helix. However, because the bands assigned to the alpha-helix and
      random coil structures are overlapped in the spectra, the content of random coil
      structures in Cu(4)Zn(3)MT-III is therefore higher than those in Cd(5)Zn(2)MT-I,
      Cd(5)Zn(2)MT-II, and Zn(7)MT-I.

PMID- 12209459
TI  - Spin trapping study of reactive oxygen species formation during bopindolol
      peroxidation.
AB  - The generation of singlet molecular oxygen ((1)O(2)) and hydroxyl radicals (HO*)
      during peroxidation of bopindolol in the presence of Co(II) ions was studied
      using electron spin resonance (ESR) and spectrophotometry methods. 2,2,6,6
      Tetramethyl-4-piperidone and 5,5-dimethyl-1-pyrroline-1-oxide were used as traps.
      The spectrophotometry determination of (1)O(2) was based on bleaching of p
      nitrosodimethylaniline (RNO), which was caused by the product of the reaction of
      (1)O(2) with imidazole and was followed by monitoring the decrease in optical
      density at 440 nm. The effect of (1)O(2) quenchers and oxygen free radical
      scavengers on the ESR signal and the bleaching of RNO was studied. The data
      presented here give new evidence for generation of the reactive oxygen species
      during peroxidation of bopindolol.

PMID- 12209460
TI  - Multinuclear NMR and FTIR studies of new polyoxaalkyl esters of lasalocid and
      their complexes with lithium and sodium cations.
AB  - Three new polyoxaalkyl esters of lasalocid are synthesized. Their ability to form
      complexes with Li(+) and Na(+) cations is studied using multinuclear NMR methods,
      FTIR spectroscopy in the middle and far IR regions, and mass spectrometry. It is
      found that lasalocid esters form only 1:1 complexes with the metal cations. The
      results of the NMR study in pyridine show that the polyoxaalkyl chain of the
      ester does not influence the complex formation of the lasalocid part of the
      esters. The reason for this is the competition of the pyridine molecules in the
      complexation process of metal cations. In chloroform the properties of the
      complex formation have changed and the oxaalkyl chain plays an important role
      within the complexation process, as demonstrated by the dependence of the
      respective continuous absorptions in the far IR region on the length of the
      oxaalkyl chain (i.e., on the number of the oxygen atoms in the chain). The
      modifications of the lasalocid molecule influences the complexation of the metal
      cation and probably the interactions with the membrane. An increase in antibiotic
      activity is found as a consequence of these changed interactions.

PMID- 12209461
TI  - Spectroscopic studies and PM5 semiempirical calculations of new Schiff bases of
      gossypol with polyoxaalkylamines.
AB  - Three Schiff bases of racemic gossypol with polyoxaalkylamines were synthesized
      and studied by FTIR and (1)H-NMR spectroscopy, and their structures were
      calculated by the PM5 semiempirical method. These Schiff bases exist in the solid
      state and in solutions as enamine forms. An increasing length of the polyoxaalkyl
      chain causes the increase of the interaction of the oxygen atoms of this chain
      with the OH groups in the 6,6' positions. This interaction is very well evidenced
      in the FTIR and (1)H-NMR spectra. The structures of the Schiff bases and the
      hydrogen bonds within these structures are discussed.

PMID- 12209462
TI  - Surface fluorescence resonance energy transfer studies on interfacial adsorption
      of Thermomyces (humicola) lanuginosa lipase, using monomolecular films of cis
      parinaric acid.
AB  - The fluorescence resonance energy transfer (FRET) technique was adapted to study
      the process whereby lipase is adsorbed to monomolecular lipid films spread at the
      air-water interface. When cis-parinaric acid (cis-PnA) was spread over an aqueous
      subphase before the injection of sodium taurodeoxycholate (NaTDC) and Thermomyces
      lanuginosa lipase (TLL), no FRET was observed. Under these conditions, no
      adsorption of TLL was detected using an ELISA. In contrast, FRET occurred when
      cis-PnA was spread over an aqueous subphase containing NaTDC and TLL. The FRET
      signals observed were attributed to the interactions between the adsorbed TLL and
      the cis-PnA monomolecular films. Comparisons between the fluorescence emission
      spectra corresponding to the bulk phase and the aspirated film, in the presence
      and absence of TLL, showed that cis-PnA was undetectable in the bulk phase. We
      concluded that the FRET originated from the interface and not from the bulk
      phase. Using surface FRET, we estimated that the surface excess of the
      catalytically inactive mutant, TLL(S146A), was 1.6 higher than that present in
      the wild-type TLL. This finding is in agreement with independent measurements of
      the surface excess of TLL and TLL(S146A) on monomolecular films of cis-PnA.

PMID- 12209463
TI  - Fourier transform IR study of aggregational behavior of N-acetyl-L- and N
      butyloxycarbonyl-L-glutamic acid oligomeric benzyl esters in dioxane and benzene:
      beta-turn --> antiparallel beta-sheet transition.
AB  - Oligomeric N-acetyl-L-glutamic acid benzyl esters (AN(p)Z) with exact residue
      numbers (N(p) = 2, 3, 4, and 5) and N-butyloxycarbonyl-L-glutamic acid benzyl
      esters (BOCN(p)Z) with exact residue numbers (N(p) = 4, 5, 6, and 8) are
      synthesized by a stepwise procedure in a liquid phase. The aggregational behavior
      of these oligomeric molecules in dioxane and benzene is examined by Fourier
      transform IR spectra. In particular, the concentration dependence of the IR
      spectra for the AN(p)Z solutions with N(p) values of 4 (A4Z) and 5 (A5Z) shows
      that the predominant antiparallel beta-sheet structure is stabilized above the
      critical aggregation concentration (cac), while other conformations including
      beta-turns may coexist below the cac. This fact provides evidence that
      aggregation induces the conformational transition from other conformers (probably
      beta-turns) to an antiparallel beta-sheet form. The IR results for the A3Z and
      A2Z solutions indicate that specific conformers (beta-turns), which are different
      from the beta-sheet structure, may be preferentially stabilized upon aggregation.
      Thus, the critical residue number of the AN(p)Z oligopeptides, which is essential
      for formation of a rodlike aggregate in dioxane and benzene, is 4 or 5.

PMID- 12209464
TI  - Conformational studies of wheat flour high relative molecular mass glutenin
      subunits by circular dichroism spectroscopy.
AB  - Conformational studies of 1Dx2, 1Bx7, and 1Dy12 high relative molecular mass
      glutenin subunits, extracted from Alisei 1 flour, are reported. Circular
      dichroism (CD) spectroscopy is employed to study their conformational
      polymorphism induced by urea and by urea in the presence of 1% sodium dodecyl
      sulfate (SDS). The CD spectra indicate that SDS promotes ordered structures. The
      addition of urea to the SDS-acetate solution of 1Dx2, 1Bx7, and 1Dy12 subunits
      eliminates the effect of SDS. Its addition to the acetate solution of proteins
      induces conformational transitions to form a poly-L-proline II-like structure.
      All the changes induced by urea follow a multistep transition process that is
      typical of proteins consisting of different domains.

PMID- 12209465
TI  - Effects of aminooxy analogues of biogenic polyamines on aggregation and stability
      of calf thymus DNA.
AB  - The effect of a series of aminooxy analogues of the biogenic polyamines
      spermidine and spermine on the conformation of calf thymus DNA is studied. These
      new molecules are isosteric and charge insufficient analogues that are suitable
      to study the roles of both charge distribution and structural requirements in the
      molecular physiology of the biogenic polyamines. They are also evidenced as
      useful tools to inhibit polyamine biosynthesis and cell growth. Circular
      dichroism (CD) spectra of solutions containing DNA and the aminooxy analogues at
      different concentrations (100-1000 microM) and different pH values, (5-7.5) are
      recorded. We use both sonicated and highly polymerized calf thymus DNA. The CD
      spectra of sonicated DNA showed the formation of Psi-DNA, a highly ordered
      aggregated structure similar to liquid crystals, in the presence of the aminooxy
      analogues. Aggregation induced by an aminooxy derivative of spermine is followed
      by DNA collapse when increasing the polyamine concentration. The features of Psi
      DNA are not detected for highly polymerized DNA. Temperature melting measurements
      support a high degree of structural order of the aggregates. The CD experiments
      indicate that dications are unable to induce major changes on the macromolecular
      structure of DNA. In addition, aggregation is only observed when the trimethylene
      moiety is present between two adjacent positive charges. The observed differences
      among the CD spectra of DNA solutions with different aminooxy derivatives of
      spermidine indicate different roles for different amino groups of this biogenic
      polyamine when interacting with DNA. Our results support the idea that aminooxy
      analogues can be used as good models in studying the physiological functions of
      biogenic polyamines.

PMID- 12209466
TI  - Study of wheat high molecular weight 1Dx5 subunit by (13)C and (1)H solid-state
      NMR. II. Roles of nonrepetitive terminal domains and length of repetitive domain.
AB  - This work follows a previous article that addressed the role of disulfide bonds
      in the behavior of the 1Dx5 subunit upon hydration. Here the roles of
      nonrepetitive terminal domains present and the length of the central repetitive
      domain in the hydration of 1Dx5 are investigated. This was achieved by comparing
      the hydration behavior of suitable model samples determined by (13)C- and (1)H
      NMR: an alkylated 1Dx5 subunit (alk1Dx5), a recombinant 58-kDa peptide
      corresponding to the central repetitive domain of 1Dx5 (i.e., lacking the
      terminal domains), and two synthetic peptides (with 6 and 21 amino acid residues)
      based on the consensus repeat motifs of the central domain. The (13)C cross
      polarization and magic angle spinning (MAS) experiments recorded as a function of
      hydration gave information about the protein or peptide fractions resisting
      plasticization. Conversely, (13)C single pulse excitation and (1)H-MAS gave
      information on the more plasticized segments. The results are consistent with the
      previous proposal of a hydrated network held by hydrogen-bonded glutamines and
      possibly hydrophobic interactions. The nonrepetitive terminal domains were found
      to induce water insolubility and a generally higher network hindrance. Shorter
      chain lengths were shown to increase plasticization and water solubility.
      However, at low water contents, the 21-mer peptide was characterized by higher
      hindrance in the megahertz and kilohertz frequency ranges compared to the longer
      peptide; and a tendency for a few hydrogen-bonded glutamines and hydrophobic
      residues to remain relatively hindered was still observed, as for the protein and
      large peptide. It is suggested that this ability is strongly dependent on the
      peptide primary structure.

PMID- 12209468
TI  - Sequence-specific recognition of DNA by hydrophobic, alanine-rich mutants of the
      basic region/leucine zipper motif investigated by fluorescence anisotropy.
AB  - We generated minimalist proteins capable of sequence-specific, high-affinity
      binding of DNA to probe how proteins are used and can be used to recognize DNA.
      In order to quantify binding affinities and specificities in our protein-DNA
      system, we used fluorescence anisotropy to measure in situ the thermodynamics of
      binding of alanine-rich mutants of the GCN4 basic region/leucine zipper (bZIP)
      domain to DNA duplexes containing target sites AP-1 (5'-TGACTCA-3') or ATF/CREB
      (5'-TGACGTCA-3'). We simplified the alpha-helical bZIP molecular recognition
      scaffold by alanine substitution: 4A, 11A, and 18A contain four, eleven, and
      eighteen alanine mutations in their DNA-binding basic regions, respectively.
      DNase I footprinting analysis demonstrates that all bZIP mutants retain the
      sequence-specific DNA-binding function of native GCN4 bZIP. Titration of
      fluorescein-labeled oligonucleotide duplexes with increasing amounts of protein
      yielded low nanomolar dissociation constants for all bZIP mutants in complex with
      the AP-1 and ATF/CREB sites: binding to the nonspecific control duplex was > 1000
      fold weaker. Remarkably, the most heavily mutated protein 18A, containing 24
      alanines in its 27-residue basic region, still binds AP-1 and ATF/CREB with
      dissociation constants of 15 and 7.8 nM, respectively. Similarly, wild-type bZIP
      binds these sites with K(d) values of 9.1 and 14 nM. 11A also displays low
      nanomolar dissociation constants for AP-1 and ATF/CREB, while 4A binds these
      sites with approximately 10-fold weaker K(d) values. Thus, both DNA-binding
      specificity and affinity are maintained in all our bZIP derivatives. This Ala
      rich scaffold may be useful in design and synthesis of small alpha-helical
      proteins with desired DNA-recognition properties capable of serving as
      therapeutics targeting transcription.

PMID- 12209467
TI  - Polysaccharide-polynucleotide complexes VIII. Cation-induced complex formation
      between polyuridylic acid and schizophyllan.
AB  - Schizophyllan belongs to the beta-1,3-D-glucan family, and dissolves as a single
      chain in dimethyl sulfoxide (DMSO) and as a triple helix in water, respectively.
      It is already known that when we prepare a mixture of poly(C) and schizophyllan
      in DMSO and subsequently exchange the solvent to water, poly(C) and schizophyllan
      can form a complex. When we applied this procedure to the poly(U) system, we
      could not induce the complex formation between poly(U) and schizophyllan at all.
      However, we found that addition of some alkaline cations is necessary to induce
      the complexation between poly(U) and schizophyllan. The complex stability
      strongly depends on both the cation species and the salt concentration. The
      complexation is sensitively reflected in the CD spectrum. The magnitude of the
      spectral change is followed by the order; Rb(+) >> K(+) > Na(+) ? Cs(+). This
      cation order in the stability is confirmed by the fluorescence polarization
      measurements. (23)Na-NMR spectroscopy reveals that the product system is
      stabilized by addition of the cations, suggesting that the OH group in
      schizophyllan and the phosphate anion in poly(U) synergistically form a specific
      ligand system for the cations. To the best of our knowledge, such a cation
      induced specific interaction between saccharides and polynucleotides has not been
      reported, and may provide a new clue to understand the biological role of beta
      1,3-D-glucans.

PMID- 12209469
TI  - Trifluoroethanol and binding to model membranes stabilize a predicted turn in a
      peptide corresponding to the first extracellular loop of the angiotensin II
      AT(1A) receptor.
AB  - Homology modeling of the angiotensin II AT(1A) receptor based on rhodopsin's
      crystal structure has assigned the 92-100 (YRWPFGNHL) sequence of the receptor to
      its first extracellular loop. Solution and membrane-bound conformational
      properties of a peptide containing this sequence (EL1) were examined by CD,
      fluorescence, and (1)H-NMR. CD spectra in aqueous solution revealed an
      equilibrium between less organized and folded conformers. NMR spectra indicated
      the coexistence of trans and cis isomers of the Trp(3)-Pro(4) bond. A positive
      band at 226 nm in the CD spectra suggested aromatic ring stacking, modulated by
      EL1's ionization degree. CD spectra showed that trifluoroethanol (TFE), or
      binding to detergent micelles and phospholipid bilayers, shifted the equilibrium
      toward conformers with higher secondary structure content. Different media gave
      rise to spectra suggestive of different beta-turns. Chemical shift changes in the
      NMR spectra corroborated the stabilization of different conformations. Thus,
      environments of lower polarity or binding to interfaces probably favored the
      formation of hydrogen bonds, stabilizing beta-turns, predicted for this sequence
      in the whole receptor. Increases in Trp(3) fluorescence intensity and anisotropy,
      blue shifts of the maximum emission wavelength, and pK changes also evinced the
      interaction between EL1 and model membranes. Binding was seen to depend on both
      hydrophobic and electrostatic interactions, as well as lipid phase packing.
      Studies with water-soluble and membrane-bound fluorescence quenchers demonstrated
      that Trp(3) is located close to the water-membrane interface. The results are
      discussed with regard to possible implications in receptor folding and function.

PMID- 12209470
TI  - Determination of isokinetic ratios necessary for equimolar incorporation of
      carboxylic acids in the solid-phase synthesis of mixture-based combinatorial
      libraries.
AB  - The methods used to study the relative reaction rates of 45 different aliphatic
      and aromatic carboxylic acids when coupled to resin-bound amino acid amides is
      described. Competition experiments involving the coupling of incoming carboxylic
      acids to resin-bound amino acid amides were performed. The relative composition
      of each N-acylated amino acid amide in the resulting mixtures was compared to
      controls prepared by physically mixing equal aliquots of individual compounds in
      order to study the relative reaction rates of the incoming carboxylic acids. The
      ratios of the incoming carboxylic acids were then iteratively adjusted to yield
      as close to equimolar products as possible. As expected, the steric and
      electronic nature of the incoming carboxylic acids was found to influence their
      relative reaction rates. The steric hindrance of the resin-bound amino acid
      appears to have a proportional effect on the reaction rates of the incoming
      carboxylic acids. N-acylated amino acid amides in the final mixtures, prepared
      using the final isokinetic ratios, were found to be approximately equimolar.

PMID- 12209471
TI  - DNA melting in the presence of fluorescent intercalating oxazole yellow dyes
      measured with a gel-based assay.
AB  - We measured the effect of the intercalating oxazole yellow DNA dye quinolinium,4
      [(3-methyl-2(3H)-benzoxazolylidene)methyl]-1-[3-(trimethylammonio)propyl]
      ,diiodide (YO-PRO) and its homodimer (YOYO) on the melting of self-complementary
      DNA duplexes using a gel-based assay. The assay, which requires a self
      complementary DNA sequence, is independent of the optical properties of the
      molecules in solution. The melting temperature of the DNA is observed to increase
      in direct proportion to the number of occupied intercalation sites on the DNA,
      irrespective of whether the dye molecules are in monomer or dimer form. The
      increase is approximately 2.5 degrees C for each intercalation site occupied in
      the presence of 38 mM [Na(+)], for dye/duplex ratios in which less than 1/5 of
      the available intercalation sites are occupied.

PMID- 12209472
TI  - Ab initio quantum mechanical models of peptide helices and their vibrational
      spectra.
AB  - Structural parameters for standard peptide helices (alpha, 3(10), 3(1) left
      handed) were fully ab initio optimized for Ac-(L-Ala)(9)-NHMe and for Ac-(L
      Pro)(9)-NHMe (poly-L-proline-PLP I and PLP II-forms), in order to better
      understand the relative stability and minimum energy geometries of these
      conformers and the dependence of the ir absorption and vibrational CD (VCD)
      spectra on detailed variation in these conformations. Only the 3(10)-helical Ala
      based conformation was stable in vacuum for this decaamide structure, but both
      Pro-based conformers minimized successfully. Inclusion of solvent effects, by use
      of the conductor-like screening solvent model (COSMO), enabled ab initio
      optimizations [at the DFT/B3LYP/SV(P) level] without any constraints for the
      alpha- and 3(10)-helical Ala-based peptides as well as the two Pro-based
      peptides. The geometries obtained compare well with peptide chain torsion angles
      and hydrogen-bond distances found for these secondary structure types in x-ray
      structures of peptides and proteins. For the simulation of VCD spectra, force
      field and intensity response tensors were obtained ab initio for the complete Ala
      based peptides in vacuum, but constrained to the COSMO optimized torsional
      angles, due to limitations of the solvent model. Resultant spectral patterns
      reproduce well many aspects of the experimental spectra and capture the
      differences observed for these various helical types.

PMID- 12209474
TI  - Control of peptide conformation by the Thorpe-Ingold effect (C alpha
      tetrasubstitution).
AB  - The preferred conformations of peptides heavily based on the currently
      extensively exploited achiral and chiral alpha-amino acids with a quaternary
      alpha-carbon atom, as determined by conformational energy computations, crystal
      state (x-ray diffraction) analyses, and solution ((1)H-NMR and spectroscopic)
      investigations, are reviewed. It is concluded that 3(10)/alpha-helical structures
      and the fully extended (C(5)) conformation are preferentially adopted by peptide
      sequences characterized by this family of amino acids, depending upon overall
      bulkiness and nature (e.g., whether acyclic or C(alpha) (i) <--> C(alpha) (i)
      cyclized) of their side chains. The intriguing relationship between alpha-carbon
      chirality and bend/helix handedness is also illustrated. gamma-Bends and
      semiextended conformations are rarely observed. Formation of beta-sheet
      structures is prevented.

PMID- 12209475
TI  - Biophysical methods to study ligand-receptor interactions of neuropeptide Y.
AB  - Neuropeptide Y (NPY) is a 36 amino acids peptide amide that was isolated for the
      first time almost 20 years ago from porcine brain. NPY displays a multiplicity of
      physiological effects that are transmitted by at least six G-protein coupled
      receptors (GPCRs) named Y(1), Y(2), Y(3), Y(4), Y(5), and y(6). Because of the
      difficulty in obtaining high-resolution crystallographic structures from GPCRs
      that all belong to seven transmembrane helices proteins, a variety of biophysical
      methods have been applied in order to characterize the interaction of ligand and
      receptor. In this review article we present the most relevant outcomes of the
      studies performed in this field by our group and others. The use of photoaffinity
      labeling allowed the molecular characterization of the Y(2) receptor. The
      concerted application of molecular modeling and mutagenesis studies led to a
      model for the interaction of the natural agonist and nonpeptide antagonists with
      the Y(1) receptor. The three-dimensional (3D) structure and dynamics of micelle
      bound NPY and their implications for receptor selection have been studied by NMR.
      The characterization of the tertiary and quaternary structure of the NPY dimer in
      solution at millimolar concentrations has been performed by NMR and extended to
      physiologically relevant concentrations by fluorescence resonance energy transfer
      (FRET) experiments performed with fluorescence-labeled analogues.

PMID- 12209476
TI  - Amyloidogenicity and cytotoxicity of islet amyloid polypeptide.
AB  - Insoluble amyloid formation by islet amyloid polypeptide (IAPP) in the islets of
      Langerhans of the pancreas is a major pathophysiological feature of noninsulin
      dependent diabetes mellitus (NIDDM) or type II diabetes. Because in vivo formed
      amyloid colocalizes with areas of cell degeneration and IAPP amyloid aggregates
      are cytotoxic per se, the process of IAPP amyloid formation has been strongly
      associated with the progressive pancreatic cell degeneration and thus much of the
      pathology of type II diabetes. IAPP is a pancreatic polypeptide of 37 residues
      that, in its soluble form, is believed to play a role as a regulator of glucose
      homeostasis. The molecular cause and mechanism of the conversion of soluble IAPP
      into insoluble amyloid aggregates in vivo and its role in disease progress still
      remain to be clarified. Nevertheless, in the past few years significant progress
      has been made in understanding the amyloidogenesis pathway of IAPP in vitro and
      gaining insight into the structural and conformational "requirements" of IAPP
      amyloidogenesis and related cytotoxic effects. Importantly, several of the
      studies have revealed significant similarities of the above features of IAPP to
      other amyloidogenic polypeptides such as the beta-amyloid polypeptide Abeta. This
      suggests that, at the molecular level, amyloidogenesis, and possibly related cell
      degeneration and disease pathogenesis by completely different polypeptide
      sequences, may obey to common structural and conformational "rules" and follow
      similar molecular pathways. This review describes studies on the structural and
      conformational features of IAPP amyloid formation and cytotoxicity, and the
      application of the obtained knowledge for the understanding of the molecular
      mechanism of the IAPP amyloidogenesis pathway and the related cytotoxicity.

PMID- 12209477
TI  - Insect neuropeptide antagonists.
AB  - The development of a new integrated approach to the generation of a novel type of
      insect neuropeptide (Np) antagonists and putative insect control agents based on
      backbone cyclic compounds is described. The approach, termed the backbone cyclic
      neuropeptide-based antagonist (BBC-NBA), was applied to the insect pyrokinin
      (PK)/pheromone biosynthesis activating neuropeptide (PBAN) family as a model, and
      led to the discovery of a potent linear lead antagonist and several highly
      potent, metabolically stable BBC antagonists, devoid of agonistic activity, which
      inhibited PBAN-mediated activities in moths in vivo. This review briefly
      summarizes our knowledge of insect Nps, describes the PK/PBAN Np family, presents
      the basic concepts behind the BBC-NBA approach, and introduces the advantages of
      this method for generation of Np agonists, antagonists and insecticide prototype
      molecules.

PMID- 12209478
TI  - The risk of cardiovascular thrombotic events with selective cyclooxygenase-2
      inhibitors.

PMID- 12209479
TI  - Effect of urate-lowering therapy on the velocity of size reduction of tophi in
      chronic gout.
AB  - OBJECTIVE: The optimal serum urate levels necessary for elimination of tissue
      deposits of monosodium urate in patients with chronic gout is controversial. This
      observational, prospective study evaluates the relationship between serum urate
      levels during therapy and the velocity of reduction of tophi in patients with
      chronic tophaceous gout. METHOD: Sixty-three patients with crystal-confirmed
      tophaceous gout were treated with allopurinol, benzbromarone, or combined therapy
      to achieve serum uric acid levels less than the threshold for saturation of urate
      in tissues. The tophi targeted for evaluation during followup were the largest in
      diameter found during physical examination. RESULTS: Patients taking
      benzbromarone alone or combined allopurinol and benzbromarone therapy achieved
      faster velocity of reduction of tophi than patients taking allopurinol alone. The
      velocity of tophi reduction was linearly related to the mean serum urate level
      during therapy. The lower the serum urate levels, the faster the velocity of
      tophi reduction. CONCLUSION: Serum urate levels should be lowered enough to
      promote dissolution of urate deposits in patients with tophaceous gout.
      Allopurinol and benzbromarone are equally effective when optimal serum urate
      levels are achieved during therapy. Combined therapy may be useful in patients
      who do not show enough reduction in serum urate levels with single-drug therapy.

PMID- 12209480
TI  - Short-term outcomes of acute knee injuries: does the provider make a difference?
AB  - OBJECTIVE: To compare the short-term outcomes of acute knee injuries treated by
      specialists and generalists. METHODS: Using patient logs, 168 adults with acute
      knee injuries were identified; 131 (78%) completed a questionnaire 3 months after
      initial presentation. RESULTS: The mean age of the 77 male and 54 female
      responders was 34.6 years (range 18-73 years). The injuries were classified as
      mild (n = 35), moderate (n = 75), or severe (n = 21). Most responders were
      satisfied with their care and outcome, but 22% noted some functional limitations.
      The 59 patients seeing an orthopedist were more likely to have had a severe
      injury, more physician visits, activity limitations, lost time from work or
      recreation, and more pain when compared with the 72 patients who never saw an
      orthopedist. Excluding surgical patients, however, satisfaction was not
      significantly different by provider. After multivariate modeling (adjusting for
      age, sex, injury severity, and diagnosis), there was no significant association
      between having seen an orthopedist and either treatment success or satisfaction.
      CONCLUSION: With the exception of time lost for recuperation in our community
      there is little difference in short-term outcome for patients with acute knee
      injury not undergoing surgery, regardless of the specialty of the treating
      physician.

PMID- 12209481
TI  - Racial differences in social network experience and perceptions of benefit of
      arthritis treatments among New York City Medicare beneficiaries with self
      reported hip and knee pain.
AB  - OBJECTIVE: To determine whether social network experience and perceptions of
      benefit of arthritis treatments influence the decision to seek diagnosis and
      treatment. METHODS: A population-based telephone survey of 515 black and 455
      white Medicare beneficiaries was conducted. Validated questionnaires adapted for
      use in a telephone interview were used to identify people with self-reported
      symptoms of hip or knee pain. Treatment history for arthritis-related pain and
      perceptions of benefit of treatment were also assessed. RESULTS: Forty-two
      percent of blacks and 31% of whites reported hip or knee pain. Forty-two percent
      of blacks and 65% of whites reported knowing someone who had surgery for hip or
      knee pain (P < 0.0001). Blacks were less likely than whites to report that
      surgery had helped someone they knew with hip or knee pain (not significant).
      CONCLUSION: Blacks know fewer people who have had surgical treatment of hip and
      knee pain than whites and appear to be less likely to perceive that such
      treatment is beneficial.

PMID- 12209482
TI  - Acute low back pain self-management intervention for urban primary care patients:
      rationale, design, and predictors of participation.
AB  - OBJECTIVES: To describe the rationale and design of a self-management program for
      low-income, urban, primary care patients with acute low back pain. Issues related
      to recruitment and protocol delivery, and attendance patterns and predictors of
      program attendance are described. METHODS: Two hundred eleven adult patients (73%
      female; 60% African American) were recruited from primary care neighborhood
      health centers. Focus groups were conducted for program development, and
      participants then completed a baseline interview and were randomized into groups
      receiving either usual care or a self-management intervention. RESULTS: Twenty
      nine percent of the intervention group attended the self-management class.
      Significant predictors of attendance included being older, reporting less income,
      and not working for pay. Attendees did not differ from nonattendees on back pain
      severity, symptoms, health-related quality of life, self-management processes, or
      satisfaction with care. CONCLUSION: Effective minimal-contact behavioral
      interventions are needed to reach larger portions of the patient population.

PMID- 12209483
TI  - Effects of video information on preoperative anxiety level and tolerability of
      joint lavage in knee osteoarthritis.
AB  - OBJECTIVE: To investigate the impact of video information on preoperative anxiety
      of patients scheduled to undergo joint lavage for knee osteoarthritis, and
      tolerability of the lavage. METHODS: A video film on joint lavage (duration 4
      minutes, 20 seconds) was made by medical communication professionals, based on
      recommendations of the medical and paramedical staff of the Institute of
      Rheumatology. Patients diagnosed with knee osteoarthritis and scheduled for
      lavage were assigned, using a preestablished list of randomization, to either the
      video group or the no-video group. In the operating room, preoperative anxiety
      level was measured on a 100-mm visual analog scale (VAS), and tolerability was
      assessed using a 4-grade scale. RESULTS: One hundred twelve patients (56 patients
      in each group) were included and completed the trial. Preoperative anxiety was
      lower by half for patients who had viewed the video (VAS 13 +/- 20 versus 26 +/-
      27; P = 0.0056). Tolerability of knee lavage was also significantly better in the
      video group (very tolerable 91% versus 48%; P < 0.0001). CONCLUSION: This
      prospective, controlled, randomized study confirms the usefulness of video
      information prior to an invasive rheumatology procedure.

PMID- 12209484
TI  - Long-term outcome in rheumatoid arthritis: a simple algorithm of baseline
      parameters can predict radiographic damage, disability, and disease course at 12
      year followup.
AB  - OBJECTIVES: To predict the long-term outcome of rheumatoid arthritis (RA) with
      respect to radiographic damage, disability, and disease course using baseline
      variables, and to construct decision trees identifying patients on an individual
      level at the extremes of the outcome spectrum of these 3 dimensions. METHODS: The
      12-year outcome of 112 female RA patients from a prospective inception cohort was
      assessed by measuring the tertiles of radiographic damage (measured by the
      modified Sharp/van der Heijde method, SHS), disability (measured by the Health
      Assessment Questionnaire, HAQ), and severe disease course as defined by patients
      with either the 33% highest cumulative disease activity (area under the curve of
      all observed disease activity scores) or the highest tertile of radiographic
      damage. Patients in the lowest (mild) and highest tertile (severe) of each
      outcome measure were identified. All baseline parameters known to be associated
      with each outcome (demographic and socioeconomic parameters; disease duration;
      disease activity measures; laboratory measures including rheumatoid factor, HLA
      typing, percentage agalactosyl IgG, functional and radiographic measures) were
      entered into cross-validated stepwise logistic regression models to find the best
      predictive combination of baseline parameters for each of the outcomes. Using the
      results of the logistic regression models, simple decision trees were constructed
      to categorize patients at an individual level in a particular prognostic group.
      RESULTS: After 12 years, the lowest and highest tertiles were, respectively, 42.3
      and 189 for the SHS and 0.37 and 1.25 for the HAQ. Fifty-five patients had a
      severe disease course. Mild and severe radiographic damage could be predicted
      with an accuracy of 90% and 85%, respectively. Mild and severe HAQ could be
      predicted with an accuracy of 90% and 84%, respectively, and severe disease
      course with an accuracy of 81%. The baseline variables found to be predictive of
      all 3 outcome measures were very similar and consisted of combinations of the
      following baseline parameters: swollen joint count (SJC), Ritchie score,
      rheumatoid factor (RF), the presence of erosions, and the HAQ score. Additional
      knowledge of the HLA typing hardly improved the accuracy of the prediction. To
      predict outcome at the individual level, simple decision trees were constructed
      using the RF, HAQ, SJC, and presence of erosions at baseline. CONCLUSION: The
      present study shows that prediction of outcome in long-term RA is possible and
      can be done using widely available baseline parameters.

PMID- 12209485
TI  - Preferences for improved health examined in 1,024 patients with rheumatoid
      arthritis: pain has highest priority.
AB  - OBJECTIVE: To examine preferences for improved health in patients with rheumatoid
      arthritis (RA). METHODS: A survey was mailed to patients with RA enrolled in a
      county-based register. The questionnaire comprised a variety of health status
      measures (Medical Outcome Study Short Form-36, Arthritis Impact Measurement
      Scales 2 [AIMS2], Modified Health Assessment Questionnaire, and visual analog
      scale for pain and fatigue). The patients were asked to check 3 of 12 areas in
      which they would most like to see improvement (item 60 AIMS2). The number of
      respondents was 1,024 (mean age/disease duration 63.4/12.7 years, 78.7% female).
      RESULTS: Pain was the preferred area for improvement in all subgroups of
      patients. Preference for improvement in pain was associated with lower age,
      higher levels of perceived pain, and lower scores for self efficacy related to
      pain. One-third of the patients with this preference did not report use of pain
      relieving medication. CONCLUSION: Pain is the area of health in which almost 70%
      of the patients would like to see improvement. This study suggests that more
      attention should be paid to the examination of patient preferences for
      improvement in health.

PMID- 12209486
TI  - Development and evaluation of a single value score to assess global range of
      motion in juvenile idiopathic arthritis.
AB  - OBJECTIVES: To develop a global range of motion score (GROMS) and to investigate
      the association between this newly developed measure of joint range of motion and
      physical function in children with active juvenile idiopathic arthritis (JIA).
      METHODS: Two scales were calculated, 1 measuring 56 selected joints and 1
      measuring 10 joints assessed as important to function by experts from the British
      Paediatric Rheumatology Group. These were measured in 50 patients with JIA whose
      disability was assessed using the Child Health Assessment Questionnaire (CHAQ).
      RESULTS: The GROMS measuring all joints and the GROMS measuring 10 joints closely
      agreed with each other, and both GROMS correlated significantly with the CHAQ (r
      = -0.52 and -0.62, respectively). CONCLUSION: The 10-joint GROMS is a simple,
      easy-to-use tool that measures overall change in joint range of motion that
      affects physical function in JIA.

PMID- 12209487
TI  - Relationship among the HLA-DRB1 shared epitope, smoking, and rheumatoid factor
      production in rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid factor (RF) production in rheumatoid arthritis (RA) is
      generally associated with more severe disease. In some studies, RF production has
      been associated with carriage of HLA-DRB1 alleles encoding the RA-associated
      shared epitope (SE). Patients who smoke are also more likely to be RF positive.
      In this study, we investigated whether the association between RF production and
      smoking was influenced by carriage of the SE. METHODS: The smoking histories of
      371 RA patients attending a hospital clinic were recorded. RF levels and SE
      status were determined for every patient, and the associations between the SE,
      smoking, and RF production were examined. HLA-DRB1 typing was performed using
      polymerase chain reaction. Results were analyzed using chi-square tests and
      logistic regression analysis. RESULTS: Patients who had ever smoked were
      significantly more likely to be RF positive than nonsmokers (odds ratio 2.2, P <
      0.0001). This remained significant (P = 0.003) after correction for age, sex, and
      disease duration in a logistic regression model. An association was also found
      between RF positivity and carriage of the SE (P = 0.03, after correction for age,
      sex, and disease duration), but significance was reduced or lost after correction
      for previous or current smoking (P = 0.05 and 0.09, respectively). Examination of
      the major SE phenotypes in this RA population by multivariate logistic regression
      analysis revealed that only DRB1*0401 was associated with RF positivity, and that
      this was independent of the influence of smoking. CONCLUSION: Our data confirm
      that RF production in RA patients is associated with smoking. This does not
      appear to depend on an HLA-DR-restricted immune response. The association of the
      SE with RF positivity is primarily due to HLA-DRB1*0401. This appears to be
      independent of the association with smoking, although smoking further increases
      the likelihood of RF production in DRB1*0401 patients.

PMID- 12209488
TI  - Systemic lupus erythematosus in three ethnic groups. XI. Sources of discrepancy
      in perception of disease activity: a comparison of physician and patient visual
      analog scale scores.
AB  - OBJECTIVE: To compare patient's and physician's assessment of disease activity in
      a multiethnic (Hispanic, African American, and Caucasian) cohort of systemic
      lupus erythematosus (SLE) patients. METHODS: Three hundred patients with SLE from
      the LUMINA (Lupus in Minority populations: Nature versus nurture) cohort were
      included. Disease activity was assessed with the Systemic Lupus Activity Measure
      (SLAM); patients and physicians assessed disease activity using a 10-cm anchored
      visual analog scale (VAS). The difference between VAS scores was termed
      discrepancy (>1 cm was considered a priori clinically relevant). Selected
      sociodemographic, clinical, behavioral, and psychological variables were examined
      in relation to discrepancy in univariable and multivariable models adjusting for
      the physician global VAS score in order to eliminate ceiling and floor effects.
      RESULTS: A discrepancy was exhibited by 58% of the patients. Abnormal laboratory
      findings were negatively associated with discrepancy, and poor self-perceived
      functioning and joint involvement were positively associated with discrepancy.
      Ethnicity did not account for discrepant perception of disease activity.
      CONCLUSION: Patients and physicians rate disease activity in SLE differently.
      Physicians appear to place more emphasis on laboratory features while patients
      place more emphasis on function.

PMID- 12209489
TI  - Anti-beta2-glycoprotein I antibodies in pediatric systemic lupus erythematosus
      and antiphospholipid syndrome.
AB  - OBJECTIVE: To determine whether serum beta2-glycoprotein I antibody (anti
      beta2GPI) detection improves identification of pediatric subjects at risk for
      antiphospholipid syndrome (APS). METHODS: Serum antiphospholipid antibodies (aPL)
      were identified by anticardiolipin enzyme-linked immunosorbent assay (ELISA),
      lupus anticoagulant assays, and syphilis screening in children with primary APS,
      systemic lupus erythematosus (SLE), or SLE plus APS. Anti-beta2GPI level and
      isotype were determined by beta2GPI ELISA and correlated with clinical
      manifestations and other aPL assays. RESULTS: One hundred-ten subjects under 22
      years of age and of mixed ethnicity were evaluated. Fifty-seven had SLE
      (including 14 with APS), 25 had primary APS, 16 had SLE-like APS, 6 were healthy
      children with aPL detected incidentally, 4 had other rheumatic diseases and 2 had
      other conditions. Anti-beta2GPI were detected in 48% of SLE subjects and did not
      improve aPL detection over standard tests. Anti-beta2GPI were associated with
      stroke (P = 0.014), but not with other APS manifestations, and were rarely
      detected in primary APS. Among subjects with APS manifesting as chronic
      thrombocytopenia, anti-beta(2)GPI distinguished subjects with SLE from those with
      primary APS. CONCLUSIONS: With the exception of stroke, anti-beta2GPI detection
      does not improve identification of pediatric APS over that of traditional aPL
      assays. Anti-beta2GPI are rare in pediatric primary APS, but may predict
      evolution of chronic thrombocytopenia to SLE.

PMID- 12209490
TI  - Patient preferences for treatment of lupus nephritis.
AB  - OBJECTIVE: To examine the amount of improvement in renal survival that lupus
      patients require before choosing cyclophosphamide over azathioprine for the
      treatment of lupus nephritis. METHODS: Patients were presented with descriptions
      of cyclophosphamide and azathioprine and asked to indicate their preferred choice
      if each conferred an equal probability of renal survival. Strength of preference
      was assessed by systematically increasing the probability of renal survival of
      the more toxic treatment until the respondent's choice switched. RESULTS: Ninety
      three well-educated women (mean age +/- SD 40 +/- 7 years) participated in the
      study. Ninety-eight percent (91/93) of the participants chose azathioprine over
      cyclophosphamide when both drugs conferred an equal probability of renal
      survival. Although most subjects switched preferences to cyclophosphamide for
      better renal survival, 31% (28/91) were unwilling to switch from azathioprine to
      cyclophosphamide for improved short-term renal survival, and 15% (14/91) were
      unwilling to switch from azathioprine to cyclophosphamide for improved long-term
      renal survival. CONCLUSION: Although the majority of patients switched
      preferences to cyclophosphamide for better renal survival, a substantial minority
      was unwilling to accept the toxicity associated with cyclophosphamide, even if it
      was much better than azathioprine at preventing renal failure.

PMID- 12209491
TI  - Guidelines for immunologic laboratory testing in the rheumatic diseases: an
      introduction.

PMID- 12209492
TI  - Evidence-based guidelines for the use of immunologic tests: antinuclear antibody
      testing.

PMID- 12209493
TI  - Accelerated nodulosis and vasculitis following etanercept therapy for rheumatoid
      arthritis.

PMID- 12209494
TI  - What do we know about lupus membranous nephropathy? An analytic review.

PMID- 12209495
TI  - Complementary and alternative medicine use and fibromyalgia.

PMID- 12209496
TI  - Sociocultural issues in clinical research: unraveling the Tuskegee syphilis
      study.

PMID- 12209498
TI  - Choosing treatment for proliferative lupus nephritis.

PMID- 12209499
TI  - B cell-ablative therapy for the treatment of autoimmune diseases.

PMID- 12209500
TI  - Apoptosis and cellular vitality: issues in osteoarthritic cartilage degeneration.

PMID- 12209501
TI  - Pulmonary hypertension in autoimmune rheumatic diseases: where are we now?

PMID- 12209502
TI  - Mortality in early inflammatory polyarthritis: cardiovascular mortality is
      increased in seropositive patients.
AB  - OBJECTIVE: To determine the degree and causes of any excess mortality observed
      during the early years of inflammatory polyarthritis (IP). METHODS: Between 1990
      and 1994, a total of 1,236 patients were registered with the Norfolk Arthritis
      Register, a primary care-based inception cohort. All patients were tracked on the
      National Health Service Central Register for notification of death. The vital
      status of each patient was determined as of December 31, 1999. Causes of death
      were coded according to the International Classification of Diseases, Ninth
      Revision. Expected death rates were calculated using annual death rates for the
      Norfolk population. Standardized mortality ratios (SMRs) were calculated for all
      IP patients and for the subgroups of patients who did and did not satisfy the
      American College of Rheumatology (ACR) 1987 criteria for rheumatoid arthritis
      (RA) at baseline, as well as for the subgroups who were and were not rheumatoid
      factor (RF) positive at baseline. RESULTS: By December 31, 1999, 160 patients
      (13%; 79 women and 81 men) had died. The median duration of followup in the
      entire cohort was 6.9 years. Mortality rates were not significantly increased in
      the entire group of patients with IP or in the subgroup who met the ACR 1987
      criteria for RA at baseline. In contrast, RF-positive patients had an increased
      rate of death from all causes (SMR in men 1.51, in women 1.41). Cardiovascular
      disease was the most common cause of death. The majority of the excess mortality
      in the RF-positive patients could be attributed to cardiovascular causes (SMR in
      men 1.34, in women 2.02). CONCLUSION: Excess mortality in the early years of IP
      is confined to patients who are seropositive for RF. While excess cardiovascular
      mortality has been described in patients with established RA, this is the first
      report of premature death from heart disease in the early years of IP.

PMID- 12209503
TI  - Efficacy of tacrolimus in rheumatoid arthritis patients who have been treated
      unsuccessfully with methotrexate: a six-month, double-blind, randomized, dose
      ranging study.
AB  - OBJECTIVE: To assess the efficacy, safety, and optimal dose of tacrolimus
      monotherapy in patients with rheumatoid arthritis (RA). METHODS: This phase II,
      randomized, double-blind, placebo-controlled monotherapy study was set in 12
      community sites and 9 university-based sites. Two hundred sixty-eight patients
      with RA who were resistant to or intolerant of methotrexate (mean dose 15.2
      mg/week) and had active disease for at least 6 months (mean tender joint count
      28.2, mean erythrocyte sedimentation rate 46.5 mm/hour) were randomized to
      receive treatment after discontinuation of methotrexate. Those who received at
      least 1 dose of tacrolimus were analyzed; 141 completed the study. Stable dosages
      of nonsteroidal antiinflammatory drugs and low-dose prednisone were allowed
      during treatment. All patients were given 1, 3, or 5 mg of tacrolimus or placebo
      once daily for 24 weeks. The American College of Rheumatology definition of 20%
      improvement (ACR20) and the tender and swollen joint counts at the end of
      treatment were the primary outcomes. RESULTS: ACR20 response rates demonstrated a
      clear dose response. The ACR20 response was observed in 15.5% of patients
      receiving placebo (95% confidence interval [95% CI] 7.1-23.9%), 29% of the 1 mg
      tacrolimus group (95% CI 18.3-39.7%) (P < 0.058); 34.4% of the 3 mg group (95% CI
      22.7-46.0%) (P < 0.013), and 50% of the 5 mg group (95% CI 37.8-62.3%) (P < or =
      0.001). The tender joint count improved statistically significantly in all
      tacrolimus groups. The swollen joint count, physical function, and patient
      assessed pain improved statistically significantly in the 3 mg and 5 mg groups.
      The incidence of creatinine elevation > or =40% above baseline levels increased
      in a dose-dependent manner. Dropout rates were high (41-59%) and were more common
      for inefficacy in the placebo patients (71.4%), whereas they were more common for
      toxicity in the high-dose tacrolimus groups (31-33%). Discontinuation for
      creatinine elevation occurred in the 3 mg (3.1%) and 5 mg (10.9%) tacrolimus
      groups. CONCLUSION: Tacrolimus improved disease activity in methotrexate
      resistant or -intolerant patients with RA. A dose response was observed when
      efficacy and toxicity were assessed at different doses. The optimal dose of
      tacrolimus appears to be >1 mg but < or=3 mg daily.

PMID- 12209504
TI  - Efficacy of selective B cell blockade in the treatment of rheumatoid arthritis:
      evidence for a pathogenetic role of B cells.
AB  - OBJECTIVE: The pathogenetic role of B cells in rheumatoid arthritis (RA) is under
      debate, but it is currently believed to be marginal. The availability of
      selective anti-B cell treatment provides a unique opportunity to clarify this
      issue. This study was undertaken to investigate the effects of B cell blockade in
      the treatment of refractory RA, and to evaluate the implications with regard to
      the role of B cells in the disease. METHODS: Five female patients with active,
      evolving erosive RA were treated with rituximab, an anti-CD20 chimeric monoclonal
      antibody. All 5 patients had been nonresponders to combination therapy with
      methotrexate plus cyclosporin A. Two of the 5 had also failed to respond to anti
      tumor necrosis factor alpha therapy. All of these treatments were discontinued 1
      month before institution of anti-CD20 therapy. RESULTS: Marked clinical
      improvement was observed in 2 patients (American College of Rheumatology 70%
      response [ACR70] and ACR50, respectively), starting at the end of the second
      month after institution of anti-CD20 therapy (month 2) and lasting until month 10
      in 1 patient (articular relapse) and month 12 in the other (last followup). ACR20
      response was observed in 2 additional patients, lasting until month 5 and month
      7, respectively (articular relapse in both). Decrease or normalization of serum C
      reactive protein and rheumatoid factor levels were observed in these patients. In
      contrast, patient 3 had no response to the treatment. RA synovitis and evolving
      erosive damage were decreased in patients exhibiting a major response, as
      demonstrated by imaging studies. CONCLUSION: Our finding of the clinical efficacy
      of selective B cell blockade indicates that B cells play a critical role in
      rheumatoid synovitis, at least in a subset of patients. Qualitative or
      quantitative differences in B cell commitment in RA pathobiology might have a
      function in the different responses observed.

PMID- 12209505
TI  - Comparison of synovial tissues from the knee joints and the small joints of
      rheumatoid arthritis patients: Implications for pathogenesis and evaluation of
      treatment.
AB  - OBJECTIVE: Serial synovial biopsy samples are increasingly being used for the
      evaluation of novel therapies for rheumatoid arthritis (RA). Most studies have
      used tissues from knee biopsies, but technical improvements have made serial
      small joint arthroscopy feasible as well. Theoretically, there could be
      differences in the features of synovial inflammation between various joints as a
      result of mechanical factors, differences in innervation, and other factors. We
      therefore undertook this study to compare the cell infiltrate in paired synovial
      biopsy samples from inflamed knee joints and paired inflamed small joints of
      patients with RA. METHODS: Nine RA patients with both an inflamed knee joint and
      an inflamed small joint (wrist or metacarpophalangeal joint) underwent an
      arthroscopic synovial biopsy of both joints on the same day. Multiple biopsy
      specimens were collected and stained for macrophages, T cells, plasma cells,
      fibroblast-like synoviocytes, and interleukin-6 (IL-6) by immunohistochemistry.
      Sections were evaluated by digital image analysis. RESULTS: There were no
      significant differences in mean cell numbers for all markers investigated in
      samples from the knee joint compared with samples from the small joints. We
      detected statistically significant correlations for the numbers of sublining
      macrophages, T cells, and plasma cells, as well as for IL-6 expression, between
      the knee joint and the small joints. However, there was no significant
      correlation between different joints for the numbers of intimal macrophages or
      fibroblast-like synoviocytes. CONCLUSION: The results of this study show that the
      inflammation in one inflamed joint is generally representative of that in other
      inflamed joints. Therefore, it is possible to use serial samples from the same
      joint, selecting either large or small joints, for the evaluation of
      antirheumatic therapies.

PMID- 12209506
TI  - Association between tumor necrosis factor receptor II and familial, but not
      sporadic, rheumatoid arthritis: evidence for genetic heterogeneity.
AB  - OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) binds the receptors TNFRI and
      TNFRII. Results of genome scans have suggested that TNFR2 is a candidate
      rheumatoid arthritis (RA) locus. A case-control study in a UK Caucasian
      population has shown an association between a TNFR2 genotype (196R/R in exon 6)
      and familial, but not sporadic, RA. The present study was undertaken to test this
      association in the French Caucasian population. METHODS: To test for an
      association in sporadic RA, 100 families were genotyped for the 196M/R
      polymorphism and analyzed using the transmission disequilibrium test and
      haplotype relative risk. To test for an association in familial RA, RA index
      cases from 100 affected sibpair (ASP) families were genotyped for 196M/R. Linkage
      analysis was performed with 3 TNFR2 microsatellite markers. RESULTS: The TNFR2
      196R/R genotype was not associated with sporadic RA (odds ratio [OR] 0.59, P =
      0.72), but was associated with familial RA (OR 4.0, P = 0.026). The association
      was most marked in the context of TNFR2 "twin-like" RA sibs (affected sibs
      sharing both TNFR2 haplotypes) (OR 9.2, P = 0.0017). Linkage analysis results
      were consistent with the association; most of the TNFR2 linkage evidence was
      found in the subgroup of families with 196R/R ASP index cases. CONCLUSION: This
      study is the first to replicate evidence of the involvement of TNFR2 in RA
      genetic heterogeneity. Our data refine the initial hypothesis, to suggest that a
      TNFR2 recessive factor, in linkage disequilibrium with the 196R allele, plays a
      major role in a subset of families with multiple cases of RA.

PMID- 12209507
TI  - Single-nucleotide polymorphisms in tumor necrosis factor receptor genes:
      definition of novel haplotypes and racial/ethnic differences.
AB  - OBJECTIVE: To characterize allele frequencies of known single-nucleotide
      polymorphisms (SNPs) in tumor necrosis factor receptor (TNFR) genes in African
      Americans with rheumatoid arthritis (RA), healthy African Americans, and healthy
      Caucasians. METHODS: One TNFRSF1B SNP (196 G/T) that influences susceptibility to
      familial RA in Caucasians and 3 SNPs in the 5' flanking region of the TNFRSF1A
      gene (-609G/T, -580A/G, and -383A/C) were genotyped in 108 African Americans with
      RA, 62 healthy African Americans, and 59 healthy Caucasians. RESULTS: There were
      no differences in TNFRSF1A allele frequencies between African Americans with RA
      and healthy African Americans. Allele frequencies were strikingly different,
      however, between healthy African Americans and healthy Caucasians: 0.13 versus
      0.42 for -609T, 0.49 versus 0 for -580G, and 0.14 versus 0 for -383C. We
      identified 4 novel haplotypes defined by the 3 TNFRSF1A SNPs, the distribution of
      which was markedly different in healthy Caucasians and healthy African Americans
      (P = 0.000001 by chi-square test-. The frequencies of the TNFRSF1B 196 genotypes
      were similar in African Americans with RA and healthy African Americans but
      differed between healthy African Americans and healthy Caucasians (P = 0.05).
      CONCLUSION: Although we observed no associations between known TNFR SNPs or
      haplotypes and RA, significant racial differences were observed at both loci.
      Comparison of these data with other published frequencies of TNFRSF1A and
      TNFRSF1B genotypes according to race suggests that the distribution in African
      American, Caucasian, and Asian populations differs significantly. These striking
      racial/ethnic differences in TNFR SNP frequencies may influence the likelihood of
      familial RA, severe disease, or response to TNF inhibitors and may have important
      evolutionary implications.

PMID- 12209508
TI  - Detection of antibodies to deiminated recombinant rat filaggrin by enzyme-linked
      immunosorbent assay: a highly effective test for the diagnosis of rheumatoid
      arthritis.
AB  - OBJECTIVE: To assay antifilaggrin autoantibodies, we developed an enzyme-linked
      immunosorbent assay (ELISA) using a "citrullinated" recombinant rat filaggrin.
      Our objectives were to assess its value for diagnosing rheumatoid arthritis (RA)
      and to compare the results with those obtained using 4 other reference methods
      for detection of antifilaggrin autoantibodies, including the commercially
      available ELISA that uses a modified "citrullinated" synthetic peptide derived
      from the sequence of human filaggrin (CCP-ELISA). METHODS: We analyzed 711 sera
      from patients with well-characterized rheumatic diseases, including 240 patients
      with RA. Antifilaggrin autoantibodies were detected by an ELISA using a
      recombinant rat filaggrin deiminated in vitro as immunosorbent (ArFA-ELISA). The
      results considered were the differences between the optical densities obtained on
      deiminated and nondeiminated proteins. Antibodies to rat esophagus epithelium
      were detected by indirect immunofluorescence, while antibodies to human filaggrin
      were detected by immunoblotting and by a recently described ELISA using a
      deiminated recombinant human filaggrin. Finally, CCP-ELISA was performed
      according to the manufacturer's recommendations. RESULTS: At the titer thresholds
      allowing diagnostic specificities of 0.95, 0.985, and 0.99 to be reached, the
      diagnostic sensitivities of the ArFA-ELISA were 0.76, 0.67, and 0.65,
      respectively. At these 3 thresholds, the sensitivities were significantly higher
      than those of the 4 other tests. Despite incomplete overlapping of the 5 tests,
      the high diagnostic performance of the ArFA-ELISA allows us to propose this test
      to replace all the other methods for antifilaggrin autoantibody detection.
      CONCLUSION: ArFA-ELISA appears to be the most efficient test among those
      available for the detection of antifilaggrin autoantibodies, in terms of
      diagnostic accuracy for RA. Its diagnostic performance in early RA and its
      prognostic value are currently under evaluation.

PMID- 12209509
TI  - Influence of epitopes CD44v3 and CD44v6 in the invasive behavior of fibroblast
      like synoviocytes derived from rheumatoid arthritic joints.
AB  - OBJECTIVE: To investigate the functional implications of CD44 splice variant
      expression in fibroblast-like synoviocytes (FLS) obtained from patients with
      rheumatoid arthritis (RA). METHODS: FLS were isolated from synovial tissue
      obtained from both diseased and nondiseased joints. The expression of splice
      variants containing exons v3 and v6 was analyzed using immunocytochemistry with
      exon-specific antibodies and reverse transcription-polymerase chain reaction
      followed by Southern blotting. The invasive capacity of the cells was studied in
      a transwell invasion assay. RESULTS: FLS obtained from RA joints expressed
      various CD44 splicing combinations containing the variant exons v3 and/or v6.
      These cells were highly invasive, whereas cells from normal tissues, which lacked
      expression of CD44 splice variants, were not. Variant exons CD44v3 and CD44v6
      were instrumental in matrix invasion in vitro, with cells enriched for CD44v3 and
      v6 exhibiting greater invasion and antibodies that specifically recognize CD44v3
      and v6 abrogating this capacity to invade. Invasive cells showed a reduced
      expression of CD44v7/8, and antibodies against this epitope had no significant
      effect on cellular infiltration of the matrix. The antibodies had no effect on
      cell migration into the porous section of the transwell. CONCLUSION: FLS obtained
      from patients with RA express CD44 splice variants and are highly invasive,
      whereas cells obtained from healthy tissue do not express these variants and are
      not invasive. Expression of the epitopes CD44v3 and CD44v6 is instrumental in the
      invasive capacity but not in cell migration. This finding highlights a functional
      implication for the expression of CD44 splice variants at the level of matrix
      degradation.

PMID- 12209510
TI  - The determinants of change in tibial cartilage volume in osteoarthritic knees.
AB  - OBJECTIVE: The rate of change in osteoarthritic (OA) tibial articular cartilage
      and the factors that influence it are not known. We examined a cohort of subjects
      with OA to determine the change in articular knee cartilage volume over the
      course of 2 years and to identify factors which might influence such change and
      its rate. METHODS: One hundred twenty-three subjects with OA underwent baseline
      knee radiography and magnetic resonance imaging (MRI) on their symptomatic knee.
      They were followed up 2 years later with a repeat MRI of the same knee. Knee
      cartilage volume was measured at baseline and at followup. Risk factors assessed
      at baseline were tested for their association with change in knee cartilage
      volume over time. RESULTS: Mean +/- SD total tibial articular cartilage decreased
      by 5.3 +/- 5.2% (95% confidence interval [95% CI] 4.4%, 6.2%) per year. The
      annual percentages of loss of medial and lateral tibial cartilage were 4.7 +/-
      6.5% (95% CI 3.6%, 5.9%) and 5.3 +/- 7.2% (95% CI 4.1%, 6.6%), respectively.
      Initial cartilage volume was the most significant determinant of loss of tibial
      cartilage in all compartments, while age was a significant determinant of lateral
      tibial cartilage loss, when possible confounders were accounted for. CONCLUSION:
      In OA, tibial cartilage volume is lost at a rate of approximately 5% per year.
      The main factor affecting cartilage loss is initial cartilage volume. Our results
      suggest that cartilage loss may be more rapid early in disease. Further study is
      required to determine whether the rate of cartilage loss in OA is steady or
      phasic, and to identify factors amenable to intervention to reduce cartilage
      loss.

PMID- 12209511
TI  - Knee cartilage of spinal cord-injured patients displays progressive thinning in
      the absence of normal joint loading and movement.
AB  - OBJECTIVE: Alterations in the morphologic, biochemical, and mechanical properties
      of cartilage occur after unloading and immobilization in animals. However, the
      findings have been inconsistent and it is unclear whether such changes also take
      place in humans. This study tested the hypothesis that progressive thinning of
      knee joint cartilage is observed after spinal cord injury. METHODS: In this in
      vivo study, knee cartilage was assessed in patients with complete, traumatic
      spinal cord injury at 6 (n = 9), 12 (n = 11), and 24 months (n = 6) after injury.
      Morphologic parameters of the knee cartilage (mean and maximum thickness as well
      as surface area) were computed from magnetic resonance imaging (MRI) data, and
      results were compared with those in young, healthy volunteers (n = 9). RESULTS:
      After 6 months of injury, the mean articular-cartilage thickness was
      significantly less in the patella and medial tibia (decrease of 10% and 16%,
      respectively; P < 0.05), but not in the lateral tibia (decrease of 10%), compared
      with the MRI findings in healthy volunteers. After 12 and 24 months of injury,
      the differences amounted to a reduction of 21% and 23%, respectively, in the
      patella, 24% and 25%, respectively, in the medial tibia, and 16% and 19%,
      respectively, in the lateral tibia. The changes were significant in all 3
      surfaces of the spinal cord-injured joint cartilage (P < 0.05-0.01). CONCLUSION:
      Our data show, for the first time, that progressive thinning (atrophy) of human
      cartilage occurs in the absence of normal joint loading and movement. This may
      have important implications for patient management, in particular for spinal cord
      injured patients and patients who are immobilized after surgery.

PMID- 12209512
TI  - Epigallocatechin-3-gallate inhibits interleukin-1beta-induced expression of
      nitric oxide synthase and production of nitric oxide in human chondrocytes:
      suppression of nuclear factor kappaB activation by degradation of the inhibitor
      of nuclear factor kappaB.
AB  - OBJECTIVE: The proinflammatory cytokine interleukin-1beta (IL-1beta) induces the
      production of high levels of nitric oxide (NO) in human chondrocytes. Green tea
      (Camellia sinensis) polyphenols are potent antiinflammatory agents and have been
      shown to inhibit NO production in tumor cell lines. In the present study, we
      examined the effect of epigallocatechin-3-gallate (EGCG), a green tea polyphenol,
      on IL-1beta-induced production of NO in primary human osteoarthritis (OA)
      chondrocytes. METHODS: Human chondrocytes were derived from OA cartilage and were
      treated with EGCG (100 microM) and IL-1beta (2 ng/ml) for different periods, and
      inducible nitric oxide synthase (iNOS) messenger RNA and protein expression was
      determined by real-time quantitative reverse transcriptase-polymerase chain
      reaction and Western blotting, respectively. Production of NO was determined as
      nitrite in culture supernatant. Activation and translocation of nuclear factor
      kappaB (NF-kappaB), levels of inhibitor of nuclear factor kappaB (IkappaB), and
      NF-kappaB DNA binding activity were determined by Western blotting and a highly
      sensitive and specific enzyme-linked immunosorbent assay. Activity of IkappaB
      kinase was determined using in vitro kinase assay. RESULTS: Human chondrocytes
      cotreated with EGCG produced significantly less NO compared with chondrocytes
      stimulated with IL-1beta alone (P < 0.005). The inhibition of NO production
      correlated with the suppression of induction and expression of NF-kappaB
      dependent gene iNOS. EGCG inhibited the activation and translocation of NF-kappaB
      to the nucleus by suppressing the degradation of its inhibitory protein
      IkappaBalpha in the cytoplasm. CONCLUSION: Our results indicate that EGCG
      inhibits the IL-1beta-induced production of NO in human chondrocytes by
      interfering with the activation of NF-kappaB through a novel mechanism. Our data
      further suggest that EGCG may be a therapeutically effective inhibitor of IL
      1beta-induced inflammatory effects that are dependent on NF-kappaB activation in
      human OA chondrocytes.

PMID- 12209513
TI  - Sites of collagenase cleavage and denaturation of type II collagen in aging and
      osteoarthritic articular cartilage and their relationship to the distribution of
      matrix metalloproteinase 1 and matrix metalloproteinase 13.
AB  - OBJECTIVE: To determine the sites of cleavage and denaturation of type II
      collagen (CII) by collagenase(s) in healthy and osteoarthritic (OA) human
      articular cartilage and their relationship to the distribution of matrix
      metalloproteinase 1 (MMP-1) and MMP-13. METHODS: Single (per subject) full-depth
      specimens from femoral condylar cartilage were isolated from articulating
      surfaces at autopsy from 8 subjects without arthritis and during arthroplasty
      from 10 patients with OA. Fixed frozen sections of cartilage were examined by
      immunoperoxidase localization, using antibodies to the collagenase-generated
      cleavage site in CII, to an intrachain epitope recognized only in denatured CII,
      and to MMP-1 and MMP-13 (proenzyme, activated enzyme, or enzyme/inhibitor
      complex). RESULTS: Staining for collagen cleavage, denaturation, and both MMPs
      was weak to moderate and was frequently observed in pericellular sites in
      cartilage from younger, nonarthritic subjects. In specimens from older subjects,
      this staining was often more widespread and of greater intensity. Similar
      staining was usually, but not always, seen for all antibodies. In OA cartilage,
      staining was often stronger and more intense than that in normal cartilage from
      older subjects, and the distribution of staining was often similar for the
      different antibodies. Pericellular staining in the deep zone was frequently more
      pronounced in arthritic cartilage and extended to territorial and sometimes
      interterritorial sites. In very degenerate specimens, staining was distributed
      throughout most of the cartilage matrix. CONCLUSION: These observations provide
      evidence for the presence of limited cleavage and denaturation of CII restricted
      to mainly pericellular and superficial sites in cartilage from younger, healthy
      subjects, where MMP-1 and MMP-13 are also selectively localized. Collagen
      degradation is more extensive and often more pronounced in cartilage from older,
      nonarthritic subjects. Characteristic changes in early OA are similar to those
      seen with aging in cartilage from older, healthy subjects, with collagen damage
      and collagenases concentrated closer to the articular surface. There was usually
      a close correspondence between the cleavage and denaturation of CII and the sites
      at which these collagenases were detected, suggesting that both MMPs are involved
      in the physiology and pathology. There was no evidence that the damage to CII is
      ordinarily initiated in sites other than at and near the articular surface and
      around chondrocytes.

PMID- 12209514
TI  - Light-activated gene transduction enhances adeno-associated virus vector-mediated
      gene expression in human articular chondrocytes.
AB  - OBJECTIVE: To evaluate the effects of ultraviolet (UV) light as an adjuvant for
      recombinant adeno-associated virus (rAAV) transduction in human articular
      chondrocytes. METHODS: Primary articular chondrocytes and immortalized
      chondrocytes (tsT/AC62) were exposed to various doses of UV light (0-1,000
      J/m(2)) and infected at various multiplicities of infection (MOIs) with rAAV
      containing the enhanced green fluorescent protein (EGFP) gene. Cells were
      analyzed for viability and EGFP expression by fluorescence-activated cell sorting
      on days 2, 4, and 8 following infection. To evaluate the transduction efficiency
      in intact articular cartilage, full-thickness explants were exposed to UV light
      (0-200 J/m(2)), infected with rAAV-eGFP, and analyzed for transduction via
      immunohistochemistry. RESULTS: Toxicity from UV exposure was observed at doses >
      or =500 J/m(2) and > or =200 J/m(2) in primary and immortalized chondrocyte
      cultures, respectively. Transduction efficiency was dependent on the UV dose,
      MOI, and time. In the cell line, the adjuvant effect of UV on the percentage of
      cells transduced was modest, but 100 J/m(2) increased the mean fluorescence
      intensity (MFI) of the transduced cells 4-fold. In contrast, UV treatment had a
      profound effect on the transduction efficiency of primary chondrocytes, which
      reached approximately 100% after exposure to 100 J/m(2) of UV light and 10(3)
      MOIs for 8 days. Under the same conditions, 200 J/m(2) of UV light enhanced the
      MFI 7-fold. In cartilage explants, there was no difference in the number of
      transduced chondrocytes at the edge of the explants in the superficial,
      intermediate, or basal zones; however, 200 J/m(2) of UV light increased the
      transduction efficiency 2-fold at a low MOI. In the center of the explants, the
      superficial chondrocytes were efficiently transduced; those in the intermediate
      and basal zones could not be efficiently transduced under any condition. In the
      superficial chondrocytes, a low MOI and 200 J/m(2) of UV light increased the
      transduction efficiency 3-fold (to 100%). CONCLUSION: UV light at doses of up to
      200 J/m(2) (which do not significantly affect cell viability) significantly
      enhances the transduction efficiency and expression of the transduced gene in
      cultures of rAAV-infected primary chondrocytes and in chondrocytes in the
      superficial zone of intact articular cartilage. These findings support the
      concept that UV-activated gene transduction could be used as an adjuvant for in
      vivo rAAV articular cartilage gene therapy with low viral titers to prevent
      and/or treat arthritis.

PMID- 12209515
TI  - The effects of age and sex on chondroitin sulfates in normal synovial fluid.
AB  - OBJECTIVE: To examine how age and sex influence chondroitin sulfates (CS) in
      normal synovial fluid, we measured the concentrations of chondroitin 6-sulfate
      (C6S), chondroitin 4-sulfate (C4S), and hyaluronic acid (HA) in healthy subjects
      of different ages. METHODS: Synovial fluid samples were obtained from 82 healthy
      volunteers, ages 20-79 years. RESULTS: The concentrations of CS and HA and the
      C6S:C4S ratio varied with age. Their values were highest between 20 and 30 years
      of age, and thereafter they showed a tendency to decrease. Statistically, the C6S
      concentration and the C6S:C4S ratio at ages 60-70 years were significantly lower
      than those at 20-30 years of age. There was also a clear between-sex difference,
      in which the CS concentrations and the C6S:C4S ratio in women were significantly
      lower than those in men (P = 0.0003 for C6S, P = 0.02 for C4S, P = 0.002 for
      C6S:C4S ratio). In sharp contrast, little between-sex difference was found in the
      HA concentration. In multiple regression analysis, age correlated strongly with
      the C6S concentration and the C6S:C4S ratio (r = -0.521 and r = -0.617,
      respectively), weakly with the C4S concentration (r = -0.202), and moderately
      with the HA concentration (r = -0.483). Sex showed a weak correlation with the
      concentrations of C6S and C4S and the C6S:C4S ratio (r = 0.307, r = 0.225, and r
      = 0.237, respectively), and little correlation was seen between sex and the HA
      concentration. CONCLUSION: The CS concentrations and the sulfation patterns in
      normal synovial fluid vary with age and sex, and these physiologic variations
      need to be taken into account when using synovial fluid CS as markers for
      arthritic conditions.

PMID- 12209516
TI  - Identification of synovium-specific homing peptides by in vivo phage display
      selection.
AB  - OBJECTIVE: To identify homing peptides specific for human synovium that could be
      used as targeting devices for delivering therapeutic/diagnostic agents to human
      joints. METHODS: Human synovium and skin were transplanted into SCID mice. A
      disulfide-constrained 7-amino acid peptide phage display library was injected
      intravenously into the animals and synovial homing phage recovered from synovial
      grafts. Following 3-4 cycles of enrichment, DNA sequencing of homing phage clones
      allowed the identification of specific peptides that were synthesized by a
      fluorenylmethyloxycarbonyl chemistry and used in competitive in vivo assays and
      immunohistochemistry analyses. RESULTS: We isolated synovial homing phages
      displaying specific peptides that distinctively bound to synovial but not skin or
      mouse microvascular endothelium (MVE). They retained their tissue homing
      specificity in vivo, independently from the phage component, the original
      pathology of the transplanted tissue, and the degree of human/murine graft
      vascularization. One such peptide (CKSTHDRLC) maintained synovial homing
      specificity both when presented by the phage and as a free synthetic peptide. The
      synthetic peptide also competed with and inhibited in vivo the binding of the
      parent phage to the cognate synovial MVE ligand. CONCLUSION: This is the first
      report describing peptides with homing properties specific for human synovial
      MVE. This was demonstrated using a novel approach targeting human tissues,
      transplanted into SCID mice, directly by in vivo phage display selection. The
      identification of such peptides opens the possibility of using these sequences to
      construct joint-specific drug delivery systems that may have considerable impact
      in the treatment of arthritic conditions.

PMID- 12209517
TI  - Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a
      randomized trial of low-dose versus high-dose intravenous cyclophosphamide.
AB  - OBJECTIVE: Glomerulonephritis is a severe manifestation of systemic lupus
      erythematosus (SLE) that is usually treated with an extended course of
      intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen,
      we evaluated the efficacy and the toxicity of a course of low-dose IV CYC
      prescribed as a remission-inducing treatment, followed by azathioprine (AZA) as a
      remission-maintaining treatment. METHODS: In this multicenter, prospective
      clinical trial (the Euro-Lupus Nephritis Trial [ELNT]), we randomly assigned 90
      SLE patients with proliferative glomerulonephritis to a high-dose IV CYC regimen
      (6 monthly pulses and 2 quarterly pulses; doses increased according to the white
      blood cell count nadir) or a low-dose IV CYC regimen (6 fortnightly pulses at a
      fixed dose of 500 mg), each of which was followed by AZA. Intent-to-treat
      analyses were performed. RESULTS: Followup continued for a median of 41.3 months
      in the low-dose group and 41 months in the high-dose group. Sixteen percent of
      those in the low-dose group and 20% of those in the high-dose group experienced
      treatment failure (not statistically significant by Kaplan-Meier analysis).
      Levels of serum creatinine, albumin, C3, 24-hour urinary protein, and the disease
      activity scores significantly improved in both groups during the first year of
      followup. Renal remission was achieved in 71% of the low-dose group and 54% of
      the high-dose group (not statistically significant). Renal flares were noted in
      27% of the low-dose group and 29% of the high-dose group. Although episodes of
      severe infection were more than twice as frequent in the high-dose group, the
      difference was not statistically significant. CONCLUSION: The data from the ELNT
      indicate that in European SLE patients with proliferative lupus nephritis, a
      remission-inducing regimen of low-dose IV CYC (cumulative dose 3 gm) followed by
      AZA achieves clinical results comparable to those obtained with a high-dose
      regimen.

PMID- 12209518
TI  - Genetic linkage and association of Fcgamma receptor IIIA (CD16A) on chromosome
      1q23 with human systemic lupus erythematosus.
AB  - OBJECTIVE: Although low-affinity alleles of human Fcgamma receptor types IIA and
      IIIA (FcgammaRIIA and FcgammaRIIIA, respectively) polymorphisms have been
      associated with systemic lupus erythematosus (SLE) in case-control studies, the
      relative contribution of these genes to SLE susceptibility has not been resolved.
      METHODS: We analyzed the distribution of alleles of FcgammaRIIA, FcgammaRIIIA,
      and FcgammaRIIIB in 126 multiplex-SLE pedigrees and FcgammaRIIA and FcgammaRIIIA
      in a case-control replication study, using allele-specific polymerase chain
      reaction and direct sequencing of genomic DNA. Statistical tests of association
      were performed to detect evidence of linkage between the single nucleotide
      polymorphisms and SLE. RESULTS: We found evidence for linkage at both the
      FcgammaRIIIA (single-point nonparametric linkage [NPL] 1.8, P = 0.038; multipoint
      NPL 2.7, P = 0.004) and the FcgammaRIIA (single-point NPL 2.0, P = 0.021;
      multipoint NPL 2.6, P = 0.006) loci, but not the FcgammaRIIIB locus. Family-based
      tests of association demonstrated increased transmission of the low-affinity F176
      allele at the FcgammaRIIIA locus (odds ratio [OR] 2.18, P = 0.0005 by
      transmission disequilibrium test and P = 0.002, by pedigree disequilibrium test
      [PDT]), but little evidence of preferential transmission of alleles at
      FcgammaRIIA (P = 0.089 by PDT). Stratification by ethnicity showed preferential
      transmission of the associated FcgammaRIIIA allele both in families of African
      American ancestry and in those of European American ancestry. Despite significant
      linkage disequilibrium between these genes, 2- and 3-locus haplotype analysis of
      the extended Fcgamma receptor cluster did not reveal any significant association
      beyond that observed with FcgammaRIIIA alone. In a large case-control replication
      study of 438 patients with SLE and 219 controls, FcgammaRIIIA provided the
      strongest evidence of an FcgammaR-SLE association (additive model: V/V 176 versus
      V/F 176 OR 1.51, V/V 176 versus F/F 176 OR 1.98, P = 0.007). CONCLUSION: To our
      knowledge, these data are the first to demonstrate linkage and both family-based
      and case-control-based association of FcgammaRIIIA with SLE. These data provide
      genetic evidence supporting a role for the physiologically relevant single
      nucleotide polymorphism of the FcgammaRIIIA gene in the pathophysiology of this
      complex genetic disease.

PMID- 12209519
TI  - T cell receptor repertoire of T cells in the kidneys of patients with lupus
      nephritis.
AB  - OBJECTIVE: To determine the role of T cells in the pathogenesis of lupus
      nephritis (LN). METHODS: Renal biopsy specimens from 12 patients with systemic
      lupus erythematosus were used for the experiments. We analyzed T cell receptor
      (TCR) Vbeta1-20 family genes on intrarenal T cells and on peripheral blood
      lymphocytes (PBLs) by nested reverse transcriptase-polymerase chain reaction
      (PCR) and Southern blot analysis. Nucleotide sequence was determined in the third
      complementarity-determining region of the TCR Vbeta gene in expanded T cells.
      Messenger RNA (mRNA) expression levels of Th1 and Th2 cytokines on infiltrating T
      cells were measured by nested PCR. RESULTS: The repertoire of TCR Vbeta in
      intrarenal T cells was relatively restricted compared with that in PBLs. The TCR
      Vbeta8 and TCR Vbeta20 genes were preferentially expressed in 6 of 12 patients
      (50%) and the TCR Vbeta9 and TCR Vbeta14 genes were expressed in 5 of 12 patients
      (42%). Junctional sequences of complementary DNA encoding the TCR Vbeta8 and TCR
      Vbeta20 genes in intrarenal T cells showed oligoclonal expansion, indicating
      antigen-driven stimulation. Interleukin-4 (IL-4) and IL-10 mRNA were highly
      expressed on intrarenal T cells, while interferon-gamma mRNA was not detected.
      CONCLUSION: Our findings suggest that T cells infiltrating the kidneys of
      patients with LN may recognize restricted epitopes on antigens and function as
      Th2-type T cells.

PMID- 12209520
TI  - Autoantibody to c-Mpl (thrombopoietin receptor) in systemic lupus erythematosus:
      relationship to thrombocytopenia with megakaryocytic hypoplasia.
AB  - OBJECTIVE: To examine the prevalence, clinical associations, and pathogenic role
      of autoantibodies to c-Mpl, the thrombopoietin (TPO) receptor, in patients with
      systemic lupus erythematosus (SLE). METHODS: Sera from 69 SLE patients, 84
      patients with idiopathic thrombocytopenic purpura (ITP), and 60 healthy
      individuals were screened for anti-c-Mpl antibodies by enzyme-linked
      immunosorbent assay using recombinant c-Mpl as an antigen. Clinical findings,
      autoantibody profiles, and serum TPO levels were compared between SLE patients
      with and without anti-c-Mpl antibodies. A pathogenic role for the anti-c-Mpl
      antibody was evaluated by examining its inhibitory effect on TPO-dependent cell
      proliferation and megakaryocyte colony formation. RESULTS: Serum anti-c-Mpl
      antibody was detected in 8 SLE patients (11.6%) and 7 ITP patients (8.3%), but in
      none of the healthy controls. Anti-c-Mpl antibody was associated with
      thrombocytopenia (P = 0.0002) and a decrease in bone marrow megakaryocytes (P =
      0.02) in SLE patients. Serum TPO levels in thrombocytopenic SLE patients with
      anti-c-Mpl antibodies were significantly elevated compared with levels in those
      without the antibodies (P = 0.007). IgG fractions purified from anti-c-Mpl
      antibody-positive sera bound to c-Mpl expressed on the cell surface and inhibited
      TPO-dependent cell proliferation and megakaryocyte colony formation. CONCLUSION:
      Autoantibody to c-Mpl is present in a subset of SLE patients with
      thrombocytopenia and megakaryocytic hypoplasia. It is likely that the impaired
      thrombopoiesis in these patients is mediated by the anti-c-Mpl antibody, which
      functionally blocks an interaction between TPO and c-Mpl.

PMID- 12209521
TI  - Diminished peripheral blood memory B cells and accumulation of memory B cells in
      the salivary glands of patients with Sjogren's syndrome.
AB  - OBJECTIVE: To delineate the mechanism of the abnormalities in B cell biology
      found in patients with primary Sjogren's syndrome (SS). METHODS: The distribution
      of peripheral B cell subpopulations in 21 patients with primary SS was analyzed
      by immunofluorescence labeling and flow cytometry. Immunoglobulin rearrangements
      were analyzed in single B cells isolated from the peripheral blood and parotid
      glands by fluorescence-activated cell sorting. RESULTS: A significant reduction
      in the number of peripheral CD27+ memory B cells was found in SS patients,
      including a significantly reduced number of CD27+/IgD+/IgM+/CD5+ memory B cells.
      Remarkably, SS patients with secondary lymphoma uniquely exhibited an increase in
      CD27-expressing peripheral B cells, including CD27(high) plasmablasts. Molecular
      analysis for mutated Ig gene rearrangements confirmed that CD27 expression
      distinguished naive and memory cells in SS. In contrast to the peripheral blood,
      the majority of parotid B cells from 1 patient examined exhibited both the
      mutational status and phenotype of memory B cells. Accordingly, the mutational
      frequencies of V(H) rearrangements were significantly greater in parotid B cells
      than in peripheral blood B cells, whereas the V(H) gene repertoire appeared to be
      very similar between the compartments. CONCLUSION: These data indicate that there
      is an accumulation/retention of memory B cells in the inflamed salivary glands of
      SS patients. It is possible that preferential accumulation of CD27+ memory B
      cells in the inflamed parotid gland explains their reduction in the peripheral
      blood.

PMID- 12209522
TI  - HLA-B27 modulates nuclear factor kappaB activation in human monocytic cells
      exposed to lipopolysaccharide.
AB  - OBJECTIVE: To study whether HLA-B27 modifies some key factors controlling
      inflammatory responses on lipopolysaccharide (LPS) stimulation in human monocytic
      cells. METHODS: U937 human monocytic cells were stably transfected with either
      HLA-B27 genomic DNA, HLA-B27 complementary DNA, HLA-A2 genomic DNA, or with the
      resistant vector pSV2neo (mock) alone. The cells were stimulated with LPS.
      Electrophoretic mobility shift assay was performed to determine nuclear factor
      kappaB (NF-kappaB) and heat-shock factor 1 activities, Western blotting was
      performed to detect the expressions of inhibitory kappaBalpha (IkappaBalpha) and
      heat-shock proteins (HSPs), and enzyme-linked immunosorbent assay was performed
      to measure tumor necrosis factor alpha (TNFalpha) secretion. RESULTS: The
      expression of HLA-B27 modulated the response to LPS in U937 human monocytic
      cells. Stimulation with LPS led to faster degradation of IkappaBalpha regulatory
      proteins, accompanied by faster and prolonged activation of NF-kappaB in HLA-B27
      expressing cells compared with HLA-A2 and mock transfectants. The secretion of
      TNFalpha upon LPS stimulation correlated well with the activation of NF-kappaB.
      No activation of the heat-shock response was observed. CONCLUSION: Our data
      indicate that HLA-B27 has effects on host responses to LPS that are unrelated to
      antigen presentation. Two crucial events in the development of arthritis, the
      activation of NF-kappaB and the secretion of TNFalpha, were found to be enhanced
      in HLA-B27-expressing cells upon LPS stimulation. Because LPS is known to be
      present in the inflamed joints of patients with reactive arthritis (ReA), the
      enhanced inflammatory response of HLA-B27-positive cells upon LPS stimulation
      offers an attractive explanation for the role of HLA-B27 in the development of
      ReA.

PMID- 12209524
TI  - Monocytic fasciitis: a newly recognized clinical feature of tumor necrosis factor
      receptor dysfunction.
AB  - Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a
      dominantly inherited autoinflammatory syndrome that results from mutations in
      TNFRSF1A, the gene that encodes the 55-kd tumor necrosis factor receptor.
      Clinically, patients present with recurrent episodes of fever in conjunction with
      localized inflammation at various sites. Myalgia is one of the most
      characteristic features of this syndrome and is frequently associated with an
      overlying erythematous, macular rash that, together with the myalgia, displays
      centrifugal migration. This has previously been believed to occur as a result of
      myositis. We describe herein the case of a 60-year-old man with TRAPS, in whom
      magnetic resonance imaging of the left thigh demonstrated edematous changes in
      the muscle compartments and surrounding soft tissues. A full-thickness wedge
      biopsy was performed, and hematoxylin and eosin staining and immunohistochemistry
      analysis of the specimen demonstrated normal myofibrils but a severely
      destructive monocytic fasciitis. These results suggest that the myalgia
      experienced by individuals with TRAPS is due to a monocytic fasciitis and not to
      myositis.

PMID- 12209523
TI  - The enlarging clinical, genetic, and population spectrum of tumor necrosis factor
      receptor-associated periodic syndrome.
AB  - OBJECTIVE: To characterize the frequency, clinical signs, and genotypic features
      of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a
      series of 394 patients of various ethnic origins who have recurrent inflammatory
      syndromes. METHODS: Sequencing of the coding region of the TNFRSF1A gene was
      performed in 128 patients in whom there was a high suspicion of TRAPS, and
      denatured high-performance liquid chromatography was used to systematically
      screen for TNFRSF1A in 266 patients with recurrent inflammatory syndrome and no
      or only 1 Mediterranean fever gene (MEFV) mutation. RESULTS: TNFRSF1A mutations
      were found in 28 (7.1%) of 394 unrelated patients. Nine (32%) of the 28 patients
      had a family history of recurrent inflammatory syndromes. In 13 patients, the
      length of the attack of inflammation was fewer than 5 days. Three of the
      mutations (Y20H, L67P, and C96Y) were novel. Two mutations, R92Q and (mainly)
      P46L, found in 12 and 10 patients, respectively, had lower penetrance compared
      with other mutations. TNFRSF1A mutations were found in patients of various ethnic
      origins, including those at risk for familial Mediterranean fever (FMF):
      Armenians, Sephardic Jews, and especially Arabs from Maghreb. Only 3 (10.7%) of
      the 28 patients had amyloidosis. CONCLUSION: TRAPS is an underdiagnosed cause of
      recurrent inflammatory syndrome. Its presence in the population of persons of
      Mediterranean ancestry and the short duration of the attacks of inflammation can
      lead to a fallacious diagnosis of FMF. Because an accurate diagnosis in patients
      with recurrent inflammatory syndromes is crucial for proper clinical management
      and treatment, genetic screening for TNFRSF1A is warranted.

PMID- 12209525
TI  - Underutilization of gastroprotective measures in patients receiving nonsteroidal
      antiinflammatory drugs.
AB  - OBJECTIVE: To determine the frequency of use of recommended gastroprotective
      strategies in a cohort of patients receiving recurrent treatment with
      nonsteroidal antiinflammatory drugs (NSAIDs). METHODS: A cross-sectional study
      was performed using administrative data from the Tennessee Medicaid (TennCare)
      program. The study population consisted of 76,765 recurrent recipients of NSAIDs
      (NSAID users), comprising 24% of the 319,402 persons ages 50 years or older
      enrolled in the TennCare program from January 1999 through June 2000. Frequency
      of use of either of 2 recommended gastroprotective strategies, involving either
      traditional NSAIDs combined with recommended anti-ulcer cotherapy or use of a
      selective cyclooxygenase 2-inhibiting drug (coxib), was measured and categorized
      by risk for ulcer complication. RESULTS: Among this cohort of recurrent NSAID
      users, 16% received 1 of the 2 recommended gastroprotective therapies: 10%
      received traditional NSAIDs along with antiulcer drugs at the recommended doses
      and 6% received coxibs. Among those patients with > or=2 risk factors for ulcer
      complications (age 75 years or older, peptic ulcer or gastrointestinal bleeding
      in the past year, or concurrent use of oral anticoagulants or corticosteroids),
      30% received such gastroprotective therapy. CONCLUSION: Use of recommended
      strategies to decrease ulcer complications in vulnerable populations is
      relatively uncommon.

PMID- 12209526
TI  - The safety of celecoxib in patients with aspirin-sensitive asthma.
AB  - OBJECTIVE: To determine whether celecoxib, a selective cyclooxygenase 2 (COX-2)
      inhibitor, cross-reacts in patients with aspirin-exacerbated respiratory disease
      (AERD) with asthma. METHODS: Sixty patients with asthma underwent double-blinded,
      placebo-controlled oral challenges with celecoxib (100 mg, 200 mg, and 2
      placebos) over 48 hours in our General Clinical Research Center. The next day,
      sensitivity to acetylsalicylic acid (ASA) was proven in all patients with the use
      of single-blinded ASA challenges. RESULTS: None of the 60 patients experienced
      any symptoms, changes in nasal examinations, or declines in forced expiratory
      volume in 1 second during the celecoxib challenges. All 60 patients experienced
      oculonasal and/or asthmatic reactions to ASA, with a mean provoking dose of 69
      mg. The exact 1-sided confidence interval for the probability of celecoxib
      inducing cross-reactions in AERD patients was calculated to be between 0% and 5%.
      CONCLUSION: Cross-reactivity between ASA and celecoxib does not occur in patients
      with AERD. These results do not preclude the possibility of other types of immune
      reactions occurring with celecoxib after prior exposure. Our results add to the
      growing body of evidence that inhibition of COX-1 is a critical initiating event
      in the precipitation of respiratory reactions in AERD patients following
      ingestion of nonsteroidal antiinflammatory drugs.

PMID- 12209527
TI  - Cartilage-specific constitutive expression of TSG-6 protein (product of tumor
      necrosis factor alpha-stimulated gene 6) provides a chondroprotective, but not
      antiinflammatory, effect in antigen-induced arthritis.
AB  - OBJECTIVE: To study the chondroprotective effect of constitutively expressed TSG
      6 protein (tumor necrosis factor alpha-induced protein 6; Tnfip6) in cartilage,
      using antigen-induced arthritis (AIA) in mice. METHODS: Transgenic mice
      constitutively expressing TSG-6 protein in cartilage were generated. Cartilage
      specific constitutive expression of TSG-6 protein was confirmed by in situ
      hybridization, Western blot analysis, and immunohistochemistry. Control and
      transgenic mice were immunized with methylated bovine serum albumin (mBSA), and
      arthritis was induced by the intraarticular injection of mBSA. Mice were
      monitored up to day 35 after the challenge, and knee joint sections were examined
      for loss of cartilage proteoglycan (aggrecan) using Safranin O staining and
      antibodies to neoepitopes generated by various metalloproteinases (MPs). The loss
      of aggrecan in Safranin O-stained sections was quantified by morphometric
      methods. RESULTS: Tsg6/tnfip6 transgenic mice constitutively expressed
      tsg6/tnfip6 messenger RNA and corresponding TSG-6 protein in cartilage from
      embryonic life through adulthood, without any phenotypic abnormalities. These
      mice were used for AIA studies. Intraarticular injection of mBSA uniformly
      induced severe inflammation both in control (wild-type and an irrelevant
      transgenic line) mice and in tsg6/tnfip6 transgenic mice. In contrast to the mBSA
      injected knee joints of control animals that were heavily damaged from day 5, the
      cartilage of transgenic mice that constitutively expressed TSG-6 protein remained
      intact for at least 1 week, and this was followed by a relatively reduced loss of
      aggrecan. Concomitant with the loss of aggrecan, MP-generated neoepitopes
      accumulated in unprotected joints. By day 35, the proteoglycan content returned
      to nearly normal levels in tsg6/tnfip6 transgenic mice, whereas it remained low
      in MP-damaged knee cartilage of control mice. CONCLUSION: TSG-6 protein is known
      to form a complex with inter-alpha-inhibitor (IalphaI), a potent serine protease
      inhibitor, which may be immobilized via the hyaluronan (HA)-binding domain of TSG
      6 protein in the HA-rich extracellular matrix of cartilage. Thus, the local
      accumulation of TSG-6 protein and TSG-6 protein-bound IalphaI in tsg6/tnfip6
      transgenic mice may inhibit serine proteases and subsequent activation of MPs. It
      is suggested that this mechanism might protect cartilage from extensive
      degradation even in the presence of acute inflammation.

PMID- 12209528
TI  - Reduction of CpG-induced arthritis by suppressive oligodeoxynucleotides.
AB  - OBJECTIVE: Bacterial DNA contains immunostimulatory CpG motifs that cause
      inflammation when injected into the knee joints of normal mice. We examined
      whether synthetic oligodeoxynucleotides (ODN) that suppress CpG-induced immune
      responses prevent CpG-induced arthritis. METHODS: CpG, suppressive, and/or
      control ODN were injected into the knees of BALB/c mice. Joint swelling and
      inflammation were evaluated by physical measurement, by histologic analysis of
      joint tissue, and by magnetic resonance imaging. RESULTS: Immunostimulatory CpG
      DNA induced local arthritis, characterized by swelling of the knee joints, the
      presence of inflammatory cell infiltrates, the perivascular accumulation of
      mononuclear cells, and hyperplasia of the synovial lining. Administering
      suppressive (but not control) ODN reduced the manifestations and severity of
      arthritis up to 80%. CONCLUSION: Suppressive ODN may be useful for the prevention
      or treatment of arthritis induced by bacterial DNA.

PMID- 12209529
TI  - Modulation of multiple experimental arthritis models by collagen-induced
      arthritis quantitative trait loci isolated in congenic rat lines: different
      effects of non-major histocompatibility complex quantitative trait loci in males
      and females.
AB  - OBJECTIVE: Collagen-induced arthritis (CIA) is a model of inflammatory arthritis
      with many similarities to rheumatoid arthritis (RA). We previously mapped in F(2)
      offspring of CIA-susceptible DA and CIA-resistant F344 rats, 5 quantitative trait
      loci (QTLs) for which F344 alleles were associated with reduced CIA severity. In
      the present study, we sought to characterize the independent arthritis-modulating
      effects of these 5 QTLs. METHODS: CIA-regulatory regions were transferred from
      the F344 genome to the DA background or vice versa by repeated backcrossing. The
      arthritis-modulating effects of the transferred alleles were determined by
      comparing the severity of experimentally induced arthritis in congenic rats with
      that in DA rats. RESULTS: Congenic lines with either the F344 major
      histocompatibility complex (MHC) on the DA background or the DA MHC on the F344
      background were resistant to CIA, confirming both MHC and non-MHC contributions
      to the genetic regulation of CIA. F344 alleles at the Cia3 and Cia5 regions of
      chromosomes 4 and 10 reduced CIA severity relative to that observed in DA rats.
      F344 Cia4 and Cia6 regions of chromosomes 7 and 8 failed to significantly alter
      CIA severity. Arthritis-modifying effects of Cia4 and Cia6 were, however,
      detected in pristane-induced and/or Freund's incomplete adjuvant oil-induced
      arthritis. The arthritis-modifying effects of the non-MHC CIA-regulatory loci
      differed in males and females. CONCLUSION: These congenic lines confirmed the
      existence and location of genes that regulate the severity of experimental
      arthritis in rats. Mechanisms responsible for the sex-specificity of individual
      arthritis-regulatory loci may explain some of the sex differences observed in RA
      and other autoimmune diseases in humans.

PMID- 12209531
TI  - Chronic exertional compartment syndrome as a cause of bilateral forearm pain.

PMID- 12209533
TI  - 2-chloro-2'-deoxyadenosine in the treatment of Sjogren's syndrome-associated B
      cell lymphoproliferation.

PMID- 12209530
TI  - Effect of an exogenous trigger on the pathogenesis of lupus in (NZB x NZW)F1
      mice.
AB  - OBJECTIVE: This study examined the interactions between exogenous and endogenous
      factors shaping the phenotype of lupus in autoimmune (NZB x NZW)F(1) mice exposed
      to pristane, a model environmental trigger. METHODS: Frequencies of various
      autoantibodies in untreated NZB/NZW mice were determined by various means
      (immunoprecipitation, enzyme-linked immunosorbent assay [ELISA], Crithidia
      luciliae kinetoplast staining). Pristane or saline was administered
      intraperitoneally to 9-12-week-old NZB/NZW mice, followed by serial studies of
      autoantibodies, total Ig levels (ELISA), and proteinuria (dipstick). RESULTS:
      Besides antichromatin/DNA responses, NZB/NZW mice spontaneously produced novel
      autoantibodies against the double-stranded RNA binding protein RNA helicase A
      (RHA). In contrast, NZB/NZW mice (n = 70) did not produce autoantibodies against
      the nuclear RNP (nRNP), Sm, Ro, or La antigens. Pristane exposure synergistically
      activated the production of antichromatin/DNA antibodies and dramatically
      accelerated renal disease. Production of anti-nRNP/Sm and Su autoantibodies also
      was induced, indicating that the unresponsiveness of NZB/NZW mice to these
      antigens can be overcome. Curiously, pristane treatment did not enhance the
      production of anti-RHA, suggesting that these autoantibodies are regulated
      differently than anti-DNA/chromatin and Sm. In contrast to previous reports that
      suggest a critical role of deficient interleukin-12 (IL-12) production in the
      pathogenesis of lupus, there was overproduction of IL-12 in the peritoneal cavity
      of pristane-treated NZB/NZW mice, and their spleen cells also produced large
      amounts of IL-12. CONCLUSION: These data lead us to propose that environmental
      influences exacerbate autoimmune manifestations in genetically lupus-susceptible
      mice through their stimulatory effects on proinflammatory cytokines, such as IL
      12.

PMID- 12209534
TI  - Treatment with infliximab restores normal aquaporin 5 distribution in minor
      salivary glands of patients with Sjogren's syndrome.

PMID- 12209535
TI  - Clinical images: Skeletal muscle pseudo-hypertrophy in myeloma-associated
      amyloidosis.

PMID- 12209536
TI  - Rituximab for the treatment of type II mixed cryoglobulinemia.

PMID- 12209538
TI  - Anti-tumor necrosis factor therapy and Listeria monocytogenes infection: report
      of two cases.

PMID- 12209539
TI  - Bullous skin lesions following infliximab infusion in a patient with rheumatoid
      arthritis.

PMID- 12209542
TI  - Synovial lymphocyte responses to microbiologic antigen stimulation indicate the
      etiology of undifferentiated and reactive arthritis, and possibly of rheumatoid
      arthritis: Comment on the article by Schnarr et al.

PMID- 12209543
TI  - Criteria for TUNEL labeling in determining apoptosis in human osteoarthritis
      cartilage: Comment on the article by Aigner et al.

PMID- 12209545
TI  - Parvovirus B19 infection of cultured skin fibroblasts from systemic sclerosis
      patients: comment on the article by Ray et al.

PMID- 12209554
TI  - Animals in biomedical research: victories and future challenges for researchers.

PMID- 12209556
TI  - Anatomy of a successful K-12 educational outreach program in the health sciences:
      eleven years experience at one medical sciences campus.
AB  - The Department of Anatomy and Neurobiology, College of Medicine, University of
      Arkansas for Medical Sciences (UAMS) is the administrative home of a nationally
      recognized educational outreach program in the health sciences for K-12 teachers
      (includes school nurses, counselors, etc.) and students. This program is called
      the Partners in Health Sciences (PIHS) program. It began in the summer of 1991
      and is based on an annual needs assessment of the state's teachers. PIHS is a
      program available to all teachers and students in the state. It has several
      different components: (1) a cafeteria of 21 days of mini-courses offered in the
      summer to meet the professional development needs of K-12 biology/health teachers
      and other school personnel; (2) weekly, interactive telecommunication broadcasts
      for students during the academic year; (3) intensive, 5-day workshops that train
      five selected teachers at a time (10 per year) to use an authoring software
      program to develop grade-appropriate interactive, computer-assisted,
      instructional (CAI) modules for Internet (http://k14education.uams.edu) use by
      teachers and students; (4) a monthly science night for students and their parents
      at a local science magnet high school; (5) field trips to the UAMS campus for
      teachers and their students; (6) community-requested presentations by program
      faculty; and (7) availability of earning undergraduate and graduate credit for
      science education majors in the College of Education, University of Arkansas at
      Little Rock. The data presented in this report span the period from 1991 through
      2001. For all program activities, 14,084 different participants have consumed a
      total of 50,029 hours of education.

PMID- 12209557
TI  - Infective agents in fixed human cadavers: a brief review and suggested
      guidelines.
AB  - Cadavers remain a principal teaching tool for anatomists and medical educators
      teaching gross anatomy. Infectious pathogens in cadavers that present particular
      risks include Mycobacterium tuberculosis, hepatitis B and C, the AIDS virus HIV,
      and prions that cause transmissible spongiform encephalopathies such as
      Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler-Scheinker syndrome
      (GSS). It is often claimed that fixatives are effective in inactivation of these
      agents. Unfortunately cadavers, even though they are fixed, may still pose
      infection hazards to those who handle them. Specific safety precautions are
      necessary to avoid accidental disease transmission from cadavers before and
      during dissection and to decontaminate the local environment afterward. In this
      brief review, we describe the infectious pathogens that can be detected in
      cadavers and suggest safety guidelines for the protection of all who handle
      cadavers against infectious hazards.

PMID- 12209558
TI  - Development of the coronary blood supply: changing concepts and current ideas.
AB  - Earlier views of the development of the coronary vasculature included angiogenic
      budding and growth of arteries from the aortic sinuses and veins from the
      coronary sinus. The current concept begins with the establishment of the
      epicardium from the proepicardial organ, an outgrowth of the dorsal wall of the
      pericardial cavity. Capillaries form in a subepicardial mesenchymal population,
      extending as a plexus toward the truncus arteriosus and the atria. Multiple
      vessels grow from a peritruncal ring of capillaries, preferentially invading the
      newly formed aorta. In a process involving apoptotic changes of both the aortic
      wall and the invading capillaries, orifices open at the level of the aortic
      sinuses. Smooth muscle cells and pericytes, recruited from the surrounding
      mesenchyme, contribute to the vessel walls, and the definitive coronary artery
      pattern is established. Similar events are occurring on the venous side of the
      coronary circulation, following a slightly earlier time course. Multiple factors
      govern this process, including VEGF and FGF-1 stimulating vasculogenesis and
      angiogenesis, and the angiopoietins and their tyrosine kinase receptors
      modulating interactions between endothelial cells and the mural components. As
      remodeling of the capillary plexus and the coronary orifices progresses, TGF beta
      released by apoptotic cells or from other sources likely modulates VEGF and FGF
      1, and also contributes to further apoptotic changes. A better appreciation of
      the controls of the mechanisms of coronary vessel development may direct further
      research in the prevention of arteriosclerosis and ischemic tissue injuries.

PMID- 12209560
TI  - Material properties of the inner and outer cortical tables of the human parietal
      bone.
AB  - Even though the cranial vault functions as protection for the brain and as a
      support structure for facial and masticatory functions, little is known about its
      mechanical properties or their variations. The cranial vault bone is interesting
      because of its maintenance in spite of low functional strains, and because
      calvarial bone cells are often used in cell culture studies. We measured
      thickness, density, and ash weight, and ultrasonically determined elastic
      properties throughout the cortices of 10 human parietal bones. The results are
      unique for studies of the cranial vault because: 1) measurements focused
      specifically on the cortical components, 2) the orientations of the axes of
      maximum stiffness were determined before measurement of elastic properties, and
      3) two related measurements (bone density and percent ash weight) were compared.
      Results showed that the periosteal cortical plate (outer table) and the endosteal
      cortical plate (inner table) had significant differences in material properties.
      The outer table was on average thicker, denser, and stiffer than the inner table,
      which had a higher ash weight percentage. Within each table there were
      significant differences in thicknesses, ash weight percentages, and E(2)/E(3)
      anisotropies among sites. Few sites on either table had significant orientations
      of the axes of maximum stiffness. Despite this apparent randomness in
      orientation, almost all sites exhibited anisotropies equivalent to other parts of
      the skeleton.

PMID- 12209559
TI  - Survey of fibroblast growth factor expression during chick organogenesis.
AB  - Members of the extensive fibroblast growth factor (FGF) family play many key
      roles during embryonic development. In later development, during the course of
      organogenesis, these factors have been shown to direct distinct cellular pathways
      within the context of a particular organ system. To gain more insight into the
      processes that these factors may be controlling, we conducted a survey of the
      expression of known FGF family members in chick embryos at stages 18-25. We show
      the expression patterns of fgf-2, -3, -4, -8, -10, -12, -13, -14, and -18 in the
      head, trunk, limbs, heart, and tail of the embryo.

PMID- 12209561
TI  - Suppression of the melanogenic potential of migrating neural crest-derived cells
      by the branchial arches.
AB  - The development of melanocytes from neural crest-derived precursors that migrate
      along the dorsolateral pathway has been attributed to the selection of this route
      by cells that are fate-restricted to the melanocyte lineage. Alternatively,
      melanocytes could arise from nonspecified cells that develop in response to
      signals encountered while these cells migrate, or at their final destinations. In
      most animals, the bowel, which is colonized by crest-derived cells that migrate
      through the caudal branchial arches, contains no melanocytes; however, the
      enteric microenvironment does not prevent melanocytes from developing from crest
      derived precursors placed experimentally into the bowel wall. To test the
      hypothesis that the branchial arches remove the melanogenic potential from the
      crest-derived population that colonizes the gut, the Silky fowl (in which the
      viscera are pigmented) was studied. Sources of crest included Silky fowl and
      quail vagal and truncal neural folds/tubes, which were cultured or explanted to
      chorioallantoic membranes alone or together with branchial arches or limb buds
      from Silky fowl, White Leghorn, or quail embryos. Crest and mesenchyme-derived
      cells were distinguished by using the quail nuclear marker. Melanocytes developed
      from Silky fowl and quail crest-derived cells. Melanocyte development from both
      sources was inhibited by quail and White Leghorn branchial arches (and limb
      buds), but melanocyte development was unaffected by branchial arch (and limb
      buds) from Silky fowl. These observations suggest that a factor(s) that is
      normally expressed in the branchial arches, and is lacking in animals with the
      Silky mutation, prevents cells with a melanogenic potential from colonizing the
      bowel.

PMID- 12209562
TI  - Species-specific differences of myosin content in the developing cardiac chambers
      of fish, birds, and mammals.
AB  - Key morphogenetic events during heart ontogenesis are similar in different
      vertebrate species. We report that in primitive vertebrates, i.e., cartilaginous
      fishes, both the embryonic and the adult heart show a segmental subdivision
      similar to that of the embryonic mammalian heart. Early morphogenetic events
      during cardiac development in the dogfish are long-lasting, providing a suitable
      model to study changes in pattern of gene expression during these stages. We
      performed a comparative study among dogfish, chicken, rat, and mouse to assess
      whether species-specific qualitative and/or quantitative differences in myosin
      heavy chain (MyHC) distribution arise during development, indicative of
      functional differences between species. MyHC RNA content was investigated by
      means of in situ hybridisation using an MyHC probe specific for a highly
      conserved domain, and MyHC protein content was assessed by immunohistochemistry.
      MyHC transcripts were found to be homogeneously distributed in the myocardium of
      the tubular and embryonic heart of dogfish and rodents. A difference between
      atrial and ventricular MyHC content (mRNA and protein) was observed in the adult
      stage. Interestingly, differences in the MyHC content were observed at the
      tubular heart stage in chicken. These differences in MyHC content illustrate the
      distinct developmental profiles of avian and mammalian species, which might be
      ascribed to distinct functional requirements of the myocardial segments during
      ontogenesis. The atrial myocardium showed the highest MyHC content in the adult
      heart of all species analysed (dogfish (S. canicula), mouse (M. musculus), rat
      (R. norvegicus), and chicken (G. gallus)). These observations indicate that in
      the adult heart of vertebrates the atrial myocardium contains more myosin than
      the ventricular myocardium.

PMID- 12209564
TI  - Heterogeneity of chondroitin sulfate glycosaminoglycan localization during early
      development of the striped bass (Morone saxatilis).
AB  - Recent studies have suggested important functions for proteoglycan-associated
      chondroitin sulfate glycosaminoglycans (GAGs) during embryonic and larval
      development in numerous organisms, including the teleost. Little is known,
      however, about the specific distribution of different chondroitin sulfate GAGs
      during early development. The present study utilized immunohistochemistry to
      localize chondroitin sulfate GAG antigens during development of the striped bass
      (Morone saxatilis). Immunoreagents utilized were monoclonal antibodies (MAbs)
      TC2, d1C4, and CS-56, which recognize, respectively, native epitopes on
      glycosaminoglycan chains enriched in chondroitin-4-, chondroitin-6-, and both
      chondroitin-4- and -6-sulfate. Little or no immunoreactivity was observed in
      gastrulating embryos at 18 hr postfertilization with any MAb tested. By 24 hr (8
      somites), the CS-56 epitope was localized around the notochord. At hatching (48
      hr) and early larval (72 hr) stages, d1C4 and CS-56 antigens codistributed in
      some sites (e.g., the notochord and myosepta), but a striking heterogeneity of
      chondroitin sulfate GAG localization was observed in other developing tissues,
      including the eye and specific subsets of basement membrane. At these latter time
      points, TC2 reacted primarily with the extracellular matrix of the developing
      heart, particularly the ventricular and conotruncal segments. Heterogeneous
      patterning of these chondroitin sulfate GAG epitopes suggests dynamic regulation
      of proteoglycan function during critical morphogenetic events in early
      development of the striped bass.

PMID- 12209563
TI  - Localization of the transmembrane proteoglycan syndecan-4 and its regulatory
      kinases in costameres of rat cardiomyocytes: a deconvolution microscopic study.
AB  - Syndecan-4 (syn-4), a transmembrane heparan sulfate-containing proteoglycan, is
      unique among the four members of the syndecan family in its specific cellular
      localization to complex cytoskeletal adhesion sites, i.e., focal adhesions.
      During early phenotypic redifferentiation of neonatal cardiomyocytes in culture,
      immunolocalization reveals syn-4 to be heavily concentrated in the perinuclear
      endoplasmic reticulum-Golgi region, with little found at the peripheral regions.
      Subsequently, syn-4 becomes localized to a cytoskeletal adhesion complex unique
      to striated muscle, the costamere. Soon after redifferentiation of myofibrils in
      cultured neonatal cardiomyocytes, syn-4 is present only in costameres, not in
      focal adhesions. In cultured adult cardiomyocytes, it is present in both
      costameres and focal adhesions-the latter in two distinct regions of the spread
      cardiomyocytes, reflecting localization with two types of actin-containing
      filaments. The fact that syn-4 is observed early in the costameric regions, as
      opposed to later in the focal adhesions, suggests that it may play an initial
      role in early adhesion/signal transduction mechanisms in close proximity to the
      contractile apparatus, as well as in transmission of contractile force to the
      collagenous extracellular matrix (ECM) which surrounds the cardiac myofibers in
      situ. With respect to possible regulatory mechanisms of syn-4, we localized syn-4
      with both the epsilon isoform of protein kinase C and the tyrosine kinase
      pp60(csrc) in costameric regions. These findings suggest that syn-4 may not only
      play a role in cellular adhesion and contractile force transmission, it may also,
      through ser, thr, and tyr phosphorylation, be part of an interactive signal
      transduction mechanism in myocardial functioning via these adhesive cytoskeletal
      complexes.

PMID- 12209565
TI  - Dosimetry implications of upper tracheobronchial airway anatomy in two mouse
      varieties.
AB  - Strain- and variety-related differences in responses of mice have been reported
      for a variety of inhaled particulate and gaseous materials. It is important to
      understand the potential contributions to such responses of differences in
      delivered doses to the respiratory tract as well as differences in biochemical
      processes. Deposition doses of inhaled particles are influenced by several
      factors, including airway anatomy, ventilation, and particle characteristics.
      Tracheobronchial airway morphometry for airway generations 1-6 of the BALB/c
      mouse was generated using replica lung casts prepared in situ. Measurements were
      performed on two groups: control and ovalbumin-sensitized male BALB/c mice. These
      measurements were compared with previously published airway morphometry of male
      B6C3F(1) mice. Sensitization did not significantly change measured airway
      dimensions in the BALB/c mouse. However, the two mouse varieties had significant
      differences in airway anatomy. The differences found in airway anatomy between
      mouse varieties correlated with differences in body length and chest
      circumference. Particle deposition predictions for both varieties of mice were
      performed for unit density spherical particles from 0.1 to 10 microm in diameter
      at two ventilation rates using a published aerosol dosimetry computer code.
      Particle deposition in the proximal tracheobronchial tree ranged up to 3 times
      greater for the BALB/c mouse for a 2 microm particle diameter and high
      ventilation rate. These differences in predicted particle deposition suggest that
      observed strain and variety differences in response to inhaled particulate matter
      may be in part due to differences in delivered doses to the respiratory tract.

PMID- 12209566
TI  - Histochemical and ultrastructural studies of cartilage resorption and acid
      phosphatase activity during antler growth in fallow deer (Dama dama).
AB  - Cartilage resorption in forming primary fallow deer antlers was studied by
      histochemistry and electron microscopy. A high activity of tartrate-resistant
      acid phosphatase (TRAP), a histochemical marker of skeletal resorbing cells, was
      first detected in cells located in the mesenchymal tissue separating the columns
      of hypertrophic cartilage. No cartilage resorption was observed in this region.
      Intense TRAP staining occurred in large multinucleated cells (identified as
      inactive osteoclasts) as well as in smaller cells (regarded as mononuclear
      osteoclast progenitors). On the basis of these findings it was concluded that
      this was the region where osteoclasts differentiated from progenitor cells.
      Further proximally, the mineralized cartilage was eroded by active osteoclasts
      that were located in Howship's lacunae and exhibited an intense TRAP staining.
      Electron microscopy showed that the cells identified as inactive osteoclasts
      lacked a polarized organization. In contrast, the active osteoclasts in the zone
      of cartilage resorption exhibited a typical polarized organization: the nuclei
      congregated near the basolateral cell surface, and there was a zone of deep
      membrane infoldings (ruffled border) surrounded by a clear zone at the apical
      cell pole adjacent to the resorption surface of the mineralized cartilage. The
      multinucleated cartilage-resorbing cells of the forming antler thus exhibited the
      typical histochemical and morphological features of active mammalian osteoclasts.
      Low levels of TRAP activity were also observed in hypertrophic chondrocytes;
      however, the specificity and potential significance of this staining remain to be
      elucidated.

PMID- 12209567
TI  - Nitric oxide synthase in the frog cerebellum: response of Purkinje neurons to
      unilateral eighth nerve transection.
AB  - When vestibular damage occurs, nitric oxide synthase (NOS) expression in rat
      cerebellar flocculus is affected. Since compensation for postural symptoms occurs
      and Purkinje cells play an important role in movement coordination and motor
      learning, we analyzed in situ the induction of NOS in the Purkinje cell
      population of the cerebellum (corpus cerebelli) of frog after unilateral
      transection of the eighth statoacoustic nerve to gain insight into the role of NO
      in neural plasticity after injury. Three days after neurectomy, the early effects
      induced NADPH diaphorase reactivity in most of the Purkinje cells on the
      ipsilateral side, while on the contralateral side the highest labeling was
      observed at 15 days. This finding can give information on the dynamics of
      vestibular compensation, in which NOS involvement was investigated. At 30 days,
      NADPH diaphorase reactivity was present in a large number of Purkinje cells of
      the whole cerebellum, while at 60 days a down-regulation for NADPH diaphorase
      reactivity was evident. A similar trend was observed for NOS-immunoreactivity,
      which was still present at 60 days in a high percentage of Purkinje cells, mainly
      on the ipsilateral side. On the basis of cell density evaluations, it was
      proposed that the early induction of NOS after neurectomy was linked to the
      degeneration of a part of the Purkinje neurons, while the permanence of NOS
      labeling might be due to a neuroprotective role of NO in the restoration phase of
      the vestibular compensation process.

PMID- 12209569
TI  - Comparison of responses to alarm calls by patas (Erythrocebus patas) and vervet
      (Cercopithecus aethiops) monkeys in relation to habitat structure.
AB  - We studied responses to alarm calls of sympatric patas (Erythrocebus patas) and
      vervet (Cercopithecus aethiops) monkeys in relation to habitat structure, with
      the intention of understanding the relationship between the environment and
      predator avoidance. Patas and vervet monkeys are phylogenetically closely related
      and overlap in body size. However, while patas monkeys are restricted to
      nonriverine habitats at our study site, vervets use both nonriverine and riverine
      habitats, allowing us to "vary" habitat structure while controlling for effects
      of group size, composition, and phylogeny. Patas monkeys in the nonriverine
      habitat responded to mammalian predator alarm calls with a greater variety of
      responses than did vervets in the riverine habitat, but not when compared with
      vervets in the nonriverine habitat. Ecological measurements confirm subjective
      assessments that trees in the riverine habitat are significantly taller and occur
      at lower densities than trees in the nonriverine habitat. Despite the lower
      density of trees in the riverine habitat, locomotor behavior of focal animals
      indicates that canopy cover is significantly greater in the riverine than the
      nonriverine habitat. Differences in responses to alarm calls by the same groups
      of vervets in different habitat types, and convergence of vervets with patas in
      the same habitat type, suggest that habitat type can be a significant source of
      variation in antipredator behavior of primates.

PMID- 12209570
TI  - Differential skeletal preservation at Windover Pond: causes and consequences.
AB  - In this paper, we evaluate the causes of differential skeletal preservation in
      the Windover Pond skeletal series (8BR246). We collected data on sex and age for
      approximately 110 individuals, and calculated a preservation score for each
      individual based on the presence of 80 skeletal landmarks. Our research questions
      evaluated the relationship between bone preservation and individual age and sex,
      and between the presence of preserved brain material and skeletal preservation,
      and the effects of burial location on bone preservation. The results indicate
      variability in average preservation for the sample (micro = 0.53, SD = 0.22) with
      an apparent lack of sex-specific (P = 0.79) or age-specific (P = 0.37)
      differences in preservation. The relationship between brain and skeletal
      preservation (P = 0.15) was not significant. The horizontal distribution of
      burials was not significantly correlated with skeletal preservation (north: r = 
      0.10, P = 0.93; east: r = 0.09, P = 0.45); however, vertical depth was a
      significant predictor of preservation (r = -0.31, P = 0.005), indicating that
      skeletal preservation decreased as burials were located closer to the ground
      surface. The observed variability in preservation scores may be related to the
      partial drying and resubmergence of the uppermost burials for the last few
      millennia. Comparison of Windover element-specific survival rates with previous
      analyses based on terrestrial samples (Galloway et al. [1997] Forensic taphonomy,
      Boca Raton: CRC Press; Waldron [1987] Death, decay and reconstruction,
      Manchester: Manchester University Press; Willey et al. [1997] Am J Phys Anthropol
      104:513-528) affirms the relationship between element weight or density and bone
      survival. The unique taphonomic context of our study sample effected little
      change in bone deterioration processes.

PMID- 12209571
TI  - Investigation of the link between visceral surface rib lesions and tuberculosis
      in a Medieval skeletal series from England using ancient DNA.
AB  - Seven human skeletons from a large assemblage from a rural English Medieval
      burial site show lesions, predominantly proliferative in nature, on the visceral
      surfaces of the ribs. In order to investigate whether these rib lesions were
      regularly associated with tuberculous infection, these individuals, together with
      a group of age- and sex-matched control skeletons without bony signs of
      infection, were subjected to polymerase chain reaction (PCR) assays aimed at
      detecting traces of DNA from infecting microorganisms of the Mycobacterium
      tuberculosis complex. The results provided no evidence for any regular
      association between visceral surface rib lesions and the presence of M.
      tuberculosis complex DNA in the study group. The significance of these findings
      for the paleopathological interpretation of visceral surface rib lesions is
      discussed.

PMID- 12209572
TI  - Segment and joint angles of hind limb during bipedal and quadrupedal walking of
      the bonobo (Pan paniscus).
AB  - We describe segment angles (trunk, thigh, shank, and foot) and joint angles (hip,
      knee, and ankle) for the hind limbs of bonobos walking bipedally ("bent-hip bent
      knee walking," 17 sequences) and quadrupedally (33 sequences). Data were based on
      video recordings (50 Hz) of nine subjects in a lateral view, walking at voluntary
      speed. The major differences between bipedal and quadrupedal walking are found in
      the trunk, thigh, and hip angles. During bipedal walking, the trunk is
      approximately 33-41 degrees more erect than during quadrupedal locomotion,
      although it is considerably more bent forward than in normal human locomotion.
      Moreover, during bipedal walking, the hip has a smaller range of motion (by 12
      degrees ) and is more extended (by 20-35 degrees ) than during quadrupedal
      walking. In general, angle profiles in bonobos are much more variable than in
      humans. Intralimb phase relationships of subsequent joint angles show that hip
      knee coordination is similar for bipedal and quadrupedal walking, and resembles
      the human pattern. The coordination between knee and ankle differs much more from
      the human pattern. Based on joint angles observed throughout stance phase and on
      the estimation of functional leg length, an efficient inverted pendulum mechanism
      is not expected in bonobos.

PMID- 12209573
TI  - Cross-site differences in foraging behavior of white-faced capuchins (Cebus
      capucinus).
AB  - Researchers have identified a variety of cross-site differences in the foraging
      behavior of free-ranging great apes, most notably among chimpanzees (Pan
      troglodytes) and more recently orangutans (Pongo pygmaeus), that are not due to
      obvious genetic or ecological differences. These differences are often referred
      to as "traditions." What is not known is whether this high level of
      interpopulation variation in behavior is limited to hominoids. In this study, we
      use long-term data from three Costa Rican field sites that are geographically
      close and similar ecologically to identify potential foraging traditions in white
      faced capuchins (Cebus capucinus). Foraging traditions are predicted in Cebus
      because of many behavioral and morphological convergences between this genus and
      the great apes. The processing techniques used for the same food species were
      compared across sites, and all differences found were classified as present,
      habitual, or customary. Proximity data were also analyzed to determine if social
      learning mechanisms could explain variation in foraging behavior. Of the 61 foods
      compared, we found that 20 of them are processed differently by capuchins across
      sites. The differences involve pound, rub, tap, "fulcrum," "leaf-wrap," and "army
      ant following." For most of the differences with enough data to analyze, the
      average proximity score of the "matched" dyads (two individuals within a group
      who shared a "different" processing technique) was statistically higher than the
      average proximity score of the remaining "unmatched" dyads.

PMID- 12209574
TI  - Are all grandmothers equal? A review and a preliminary test of the "grandmother
      hypothesis" in Tokugawa Japan.
AB  - An unresolved question arising from human evolutionary research relates to the
      function of the postreproductive period in human females. If menopause is not
      merely an artifact resulting from the benefits of civilization, there must be an
      adaptive mechanism favoring the offspring of women who continue to thrive well
      past the time of their last ovulation. The "grandmother hypothesis" was developed
      on the basis of the original suggestion by Williams (1957 Evolution 11:32-39)
      that "stopping early" would benefit already-born children. This idea, combined
      with the concepts of kin selection (Hamilton 1964 J Theor Biol 7:1-52) and
      parental investment (Trivers 1972 Sexual Selection and the Descent of Man,
      Chicago: Aldine, p. 136-179), was expanded to suggest that postreproductive women
      (in contrast to males) contribute to their inclusive fitness by extending support
      to their grandchildren. We used discrete time event history analysis (Allison
      [1984] Event History Analysis, Newbury Park: Sage; Allison [1995] Survival
      Analysis, Cary, NC: SAS Institute) and logistic regression on data provided in
      population registers (Shumon Aratame Cho, or SAC) from a village in central
      Japan, covering the period from 1671-1871, in a preliminary investigation of the
      effects of household grandparental presence on the probability of a child's
      death. We found that after accounting for the presence of other household
      members, the only grandparent whose presence exerted a consistent negative effect
      on the likelihood of a child's death was the mother's mother. Due to the small
      sample size of households that contained maternal grandmothers, these results
      failed to achieve statistical significance. Their importance, however, is in what
      they suggest about future research, i.e., census data from preindustrial
      societies can provide a basis for testing evolutionary proposals, including the
      "grandmother hypothesis."

PMID- 12209575
TI  - ALFRED: An allele frequency database for anthropology.
AB  - The deluge of data from the human genome project (HGP) presents new opportunities
      for molecular anthropologists to study human variation through the promise of
      vast numbers of new polymorphisms (e.g., single nucleotide polymorphisms or
      SNPs). Collecting the resulting data into a single, easily accessible resource
      will be important to facilitate this research. We created a prototype Web
      accessible database named ALFRED (ALelle FREquency Database,
      http://alfred.med.yale.edu/alfred/) to store and make publicly available allele
      frequency data on diverse polymorphic sites for many populations. In constructing
      this database, we considered many different concerns relating to the types of
      information needed for anthropology, population genetics, molecular genetics, and
      statistics, as well as issues of data integrity and ease of access to data. We
      also developed links to other Web-based databases as well as procedures for
      others to make links to the data in ALFRED. Here we present an overview of the
      issues considered and provisional solutions, as well as an example of data
      already available. It is our hope that this database will be useful for research
      and teaching in a wide range of fields, and that colleagues from various fields
      will contribute to making ALFRED an important resource for many studies as yet
      unforeseen.

PMID- 12209576
TI  - Brief communication: Haplogroup X confirmed in prehistoric North America.
AB  - Haplogroup X represents approximately 3% of all modern Native North American
      mitochondrial lineages. Using RFLP and hypervariable segment I (HVSI) sequence
      analyses, we identified a prehistoric individual radiocarbon dated to 1,340 +/-
      40 years BP that is a member of haplogroup X, found near the Columbia River in
      Vantage, Washington. The presence of haplogroup X in prehistoric North America,
      along with recent findings of haplogroup X in southern Siberians, confirms the
      hypothesis that haplogroup X is a founding lineage.

PMID- 12209577
TI  - Brief communication: arboreal bipedalism in Bwindi chimpanzees.
AB  - Evidence of the form and function of bipedal behavior in nonhuman primates
      provides critical evidence to test theories about the origins of hominid
      bipedalism. Bipedalism has long been considered an evolutionarily interesting but
      rare behavior in wild chimpanzees. During May 2001, chimpanzees of the Ruhija
      community in the Bwindi Impenetrable National Park, Uganda, engaged in an
      exceptional frequency of arboreal bipedalism when feeding in large Ficus trees.
      Seventy-eight bipedal bouts of at least 5 sec duration were recorded for the
      entire community (0.49 bouts/hr), with a mean duration of 13.7 sec (+/-1.6 sec).
      The animals employed many variations on the bipedal postural theme, ranging from
      erect standing on the largest substrates while grasping overhead limbs for
      support, to standing on one leg while suspending the other leg in space, to
      extended-lean standing, in which bipedal standing transitioned into horizontal
      arm-leg suspension as the animal reached for more distant fruits. Bipedalism was
      used as part of a behavioral repertoire that integrated brachiation, four-limbed
      suspension, and forelimb-supported standing for effective small-fruit foraging.
      These observations suggest that under certain ecological conditions, arboreal
      bipedalism can be an important posture for wild chimpanzees, and may have been an
      important behavioral precursor to full terrestrial bipedalism.

PMID- 12209578
TI  - Forearm rotation and the "origin of the hominoid lifestyle": a reply to Stern and
      Larson (2001).

PMID- 12209580
TI  - Clonality of multifocal urothelial carcinomas: 10 years of molecular genetic
      studies.
AB  - Multifocal occurrence and frequent recurrence are characteristic features of
      urothelial carcinomas of both the urinary bladder and the upper urinary tract. To
      describe the clonal nature of these tumors, 2 theories have been proposed. The
      monoclonality hypothesis describes the multiple tumors as descendants of a single
      genetically transformed cell spreading throughout the urothelium. In contrast,
      field cancerization caused by carcinogen exposure of the urothelium may lead to
      independent development of synchronous or metachronous nonrelated tumors at
      different sites of the urothelial tract. In the last 10 years, a multitude of
      molecular genetic studies have investigated the clonality of multifocal
      urothelial carcinomas. The majority of studies revealed a monoclonal origin of
      the multiple tumors. However, most of these studies investigated advanced
      invasive carcinomas. A small but significant proportion of multifocal urothelial
      carcinomas appear to arise from different clones, supporting the field
      cancerization hypothesis. Oligoclonal tumors might be more common in precursor
      lesions and early tumor stages. The frequent monoclonality found in patients with
      advanced tumors could be due to outgrowth of 1 tumor cell clone with specific
      genetic alterations. Two important mechanisms appear to be important for the
      spread of malignant cells: intraluminal seeding and intraepithelial migration.
      Investigation of the entire urothelial lining in patients with urothelial tumors
      should provide further insight into the development of multifocal urothelial
      carcinomas.

PMID- 12209581
TI  - Inhibitory effect of the peptide epitalon on the development of spontaneous
      mammary tumors in HER-2/neu transgenic mice.
AB  - Female FVB/N HER-2/neu transgenic mice from the age of 2 months were
      subcutaneously injected with saline, the peptide Epitalon(R) (Ala-Glu-Asp-Gly) or
      with the peptide Vilon(R) (Lys-Glu) in a single dose of 1 microg/mouse for 5
      consecutive days every month. Epitalon treatment reduced the cumulative number
      and the maximum size of tumors (p < 0.05). Furthermore, the number of mice
      bearing 1 mammary tumor was increased, whereas the number of mice bearing 2 or
      more mammary tumors was reduced in Epitalon-treated in comparison to saline
      treated animals (p < 0.05). The size but not the number of lung metastases was
      reduced in Epitalon-treated compared to saline-treated mice (p < 0.05). The
      treatment with Vilon produced significant negative effects when compared to the
      control group, with an increased incidence of mammary cancer development (p <
      0.05), a shorter mean latent period of tumors (p < 0.05) and an increased
      cumulative number of tumors (p < 0.05). A 3.7-fold reduction in the expression of
      HER-2/neu mRNA was found in mammary tumors from HER-2/neu transgenic mice treated
      with Epitalon compared to control animals. The expression of mRNA for HER-2/neu
      was also partially reduced in Vilon-treated mice, but it remained significantly
      higher in Vilon- than in Epitalon-treated animals (1.9-fold increase). The data
      demonstrate the inhibitory effect of Epitalon in the development of spontaneous
      mammary tumors in HER-2/neu mice, suggesting that a downregulation of HER-2/neu
      gene expression in mammary adenocarcinoma may be responsible, at least in part,
      for the antitumor effect of the peptide.

PMID- 12209582
TI  - Expression of an IGF-I receptor dominant negative mutant induces apoptosis,
      inhibits tumorigenesis and enhances chemosensitivity in Ewing's sarcoma cells.
AB  - IGF-IR plays an essential role in the establishment and maintenance of the
      transformed phenotype of ES cells and interference with the IGF-IR pathways
      causes reversal of the malignant potential of this neoplasm. In this report, we
      stably transfected a dominant negative IGF-IR expression plasmid in an ES cell
      line to determine the effectiveness of this strategy against the in vitro and in
      vivo growth of ES cells. DXR sensitivity of TC-71 cells expressing dominant
      negative mutants of IGF-IR was also examined. The mutated IGF-IR that we used
      carries a mutation in the ATP-binding domain of the intracellular beta subunit,
      while the extracellular, ligand-binding alpha subunit remains unchanged. Cells
      carrying the dominant mutant IGF-IR had a marked decrease in proliferation, a
      significant increase in anoikis-induced apoptosis and a severely reduced ability
      to form colonies in soft agar. In vivo, when cells carrying dominant negative IGF
      IR were injected into nude mice, the tumor formation and metastatic abilities of
      ES cells were reduced and survival increased. Furthermore, transfected clones
      showed significantly higher sensitivity to DXR, a major drug in the treatment of
      ES. These results indicate that the IGF/IGF-IR stimulation of ES cells may be
      inhibited by expression of mutated IGF-IR on their surfaces and that this
      strategy may be considered a possible alternative to impair this important target
      of ES cells, whose therapeutic potential was further confirmed.

PMID- 12209583
TI  - Non-competitive steroid inhibition of oestrogen receptor functions.
AB  - Currently available antioestrogens, such as tamoxifen, are competitive inhibitors
      that bind to the ligand binding sites of oestrogen receptors, ERalpha and ERbeta.
      The search for alternative anti-hormone therapies is prompted by the need for
      drugs that are effective when tumours become tamoxifen resistant. The existence
      of different receptor isoforms also raise the possibility of improving
      selectivity. Earlier use of the 3beta-hydroxysteroid dehydrogenase inhibitor,
      trilostane (4alpha,5- epoxy-17beta-hydroxy-3-oxo-5alpha-androstane-2alpha
      carbonitrile), suggested that it had beneficial actions in breast cancer that
      were only partially attributable to inhibition of steroidogenesis. The present
      studies on the interactions of trilostane with oestrogen receptors show that it
      (i) inhibits oestrogen-stimulated proliferation in MCF-7 breast cancer cells,
      (ii) enhances the affinity of oestradiol binding to ER in rat uteri and
      specifically increases oestradiol binding to an ERbeta-like isoform, (iii)
      inhibits ERalpha and ERbeta binding to the classical vitellogenin gene oestrogen
      response element (ERE) and (iv) inhibits oestrogen-stimulated gene transcription
      in ERE-linked reporter systems in MCF-7 cells. The results demonstrate a novel,
      presumably allosteric, mode of antioestrogen action. The beneficial actions of
      trilostane in breast cancer may be attributed to the combination of this
      antioestrogen effect with its well documented suppression of steroidogenesis.

PMID- 12209584
TI  - Cellular effects of CPT-11 on colon carcinoma cells: dependence on p53 and hMLH1
      status.
AB  - Irinotecan (CPT-11), a recently introduced component of a standard chemotherapy
      for colorectal cancer, induces in colon cancer cell lines in vitro cell cycle
      arrest and apoptosis. Since sporadic colon carcinomas exhibit in 50-60% mutations
      in the p53 gene and in 10-15% an MSI phenotype due in the great majority of the
      cases to hMLH1 inactivation, we investigated how these lesions influence the
      cellular effects of CPT-11 by using colorectal carcinoma cell line HCT116 (which
      has the genotype p53(+/+),hMLH1(-)) and 2 derivative cell lines with the
      genotypes p53(+/+),hMLH1(+) and p53(-/-),hMLH1(-). CPT-11 treatment induced G2/M
      arrest in all 3 cell lines within 48 hr. In the p53(+/+),hMLH1(+) cell line, G2/M
      arrest was maintained for at least 12 days. There was little concomitant
      apoptosis, but this was enhanced when the hMLH1 protein was absent. This enhanced
      apoptosis was accompanied by a shorter duration of the G2/M arrest than in the
      hMLH1(+) cell line. Partial abrogation of G2/M arrest by caffeine enhanced
      apoptosis in both hMLH1(+) and hMLH1(-) cells. By contrast, in the p53(-/-) cell
      line, the G2/M arrest was terminated within 4 days. Termination of the G2/M
      arrest was accompanied by a high level of apoptosis detectable through poly(ADP
      ribose)polymerase (PARP) cleavage, DNA fragmentation and by the appearance of
      cells with a DNA content <2N. The triggering of G2/M arrest was accompanied in
      the 3 cell lines by a transient phosphorylation of cdc-2, while the maintenance
      of the arrest in the p53(+/+) cell lines was accompanied by the overexpression of
      p53 and p21 proteins and, consequently, by the inhibition of cdc-2 kinase
      activity. These data indicate that: (i) CPT-11 induces long-term arrest in
      p53(+/+) cells and a short-term arrest followed by apoptosis in p53(-/-) cells;
      (ii) triggering of the arrest is p53 independent and is associated with a brief
      increase of phosphorylation of cdc-2, while the p53-dependent maintenance of G2/M
      arrest is associated with the inhibition of cdc-2 kinase activity by p21; and
      (iii) lack of hMLH1 protein enhances CPT-11-induced apoptosis. These results may
      be useful for designing rational therapies dependent on the p53 and mismatch
      repair status in the tumor.

PMID- 12209585
TI  - VEGF isoforms and mutations in human colorectal cancer.
AB  - We wished to demonstrate vascular endothelial growth factor (VEGF) transcript
      polymorphism in human colon cancer. RNA was extracted from 25 primary human
      colorectal adenocarcinomas followed by VEGF transcript amplification, fragment
      elution, subcloning, positive selection via insert analysis and sequencing. Four
      distinct splice variants were consistently expressed in cancer, including
      VEGF121, VEGF165, VEGF189 and the newly identified truncated splice variant
      VEGF145. Six novel mutations were characterized, all of which occurred within the
      conserved expression site of the gene and which consequently were present in all
      splice forms. Five cancers exhibited single nucleotide changes and 1 cancer a 2
      nucleotide deletion. A silent mutation was observed in exon 1 at position +70
      relative to the amplification start site, a 1- and 2-base deletion with
      frameshift and protein truncation in exon 3 at positions +172 and +171/172,
      respectively, a transition mutation in exon 3 at position +248 and 2 transition
      mutations in exon 4 at positions +398 and +403. All of these sense mutations
      should alter protein conformation. To our knowledge, this is the first report of
      VEGF145 in solid malignancy. Its biologic activity remains to be determined. We
      have demonstrated a variety of sporadic mutations within human colorectal cancer
      VEGF mRNA. Mutant angiogenic VEGF may provide a genomic basis for the diversity
      of tumor-host response and may prove to be important in antisense oligonucleotide
      targeting, since all the different VEGF isoforms would have to be neutralized to
      prevent angiogenesis.

PMID- 12209587
TI  - Mutational analysis of the class I beta-tubulin gene in human breast cancer.
AB  - Non-small cell lung cancers have a high incidence of somatic mutations of the
      beta-tubulin (class I) gene, suggesting involvement in the acquisition of
      resistance to taxanes, which exert their effects through binding to beta-tubulin.
      Since taxanes are often used in the treatment of breast cancer, we carried out a
      mutational analysis of the class I beta-tubulin (GenBank accession AF070600) gene
      in breast cancer. We paid special attention to the primer design so as not to
      amplify the pseudogenes. We identified 1 somatic mutation, codon 306 [Arg (CGC)
      to Cys (TGC)], and 2 genetic polymorphisms, codon 217 [Leu (CTG) to Leu (CTA)]
      and (C to T) at 57 bases downstream from exon 4. Our results suggest that
      acquisition of resistance to taxanes is unlikely to be explained by somatic
      mutations of the class I beta-tubulin gene in most breast cancers. In addition,
      the overestimation of the incidence of somatic mutations of the class I beta
      tubulin gene due to the pseudogenes is discussed.

PMID- 12209586
TI  - Molecular analysis of lipid-depleting factor in a colon-26-inoculated cancer
      cachexia model.
AB  - Cachexia in cancer is characterized by progressive emaciation involving depletion
      of host adipose tissue stores, the molecular mechanism of which remains largely
      unknown. In this study, we have attempted to clarify the biologic characteristics
      of lipid-depleting factor in a mouse cachexia model. Utilizing differentiated 3T3
      L1 adipocytes, we established an assay method quantifying the lipid-depleting
      activity in plasma derived from colon-26-inoculated mice and then analyzed the
      associated molecular mechanism. Injection (s.c.) of a mouse colon adenocarcinoma
      cell line, colon-26 clone 20, induced cachexia, as evidenced by progressive
      weight loss. Addition of clone 20-derived cachexigenic, but not clone 5-derived
      noncachexigenic, plasma to the culture medium of differentiated 3T3-L1 adipocytes
      reduced the TG content in cultured cells. The ability of the introduced plasma to
      induce TG loss in 3T3-L1 cells paralleled the body weight changes of tumor
      inoculated host mice. Clone 20 plasma, but not clone 5 plasma or recombinant IL
      6, elicited lipolytic activity, which induced glycerol release from 3T3-L1 cells.
      Addition of clone 20 plasma to cultured 3T3-L1 adipocytes reduced TG synthesis
      from [(14)C]-glucose compared to clone 5 plasma, indicating that the lipid
      depleting activity resulting from addition of clone 20 plasma depended not only
      on induction of lipolysis but also on inhibition of lipogenesis. Addition of
      clone 20 plasma to cultured 3T3-L1 adipocytes reduced the quantity of mature
      SREBP-1 in the nucleus of 3T3-L1 cells without affecting PPAR-gamma and C/EBP
      alpha. Although TNF-alpha induced apoptosis in 3T3-L1 cells, clone 20 plasma did
      not. These results suggest that the lipid-depleting factor in clone 20 plasma is
      different from either IL-6 or TNF-alpha, and that this factor interfered with not
      only lipolysis but also lipogenesis through SREBP-1 of 3T3-L1 adipocytes.

PMID- 12209588
TI  - In vitro and in vivo characterization of graft-versus-tumor responses in melanoma
      patients after allogeneic peripheral blood stem cell transplantation.
AB  - It has been shown that after allogeneic peripheral blood stem cell
      transplantation (PBSCT), donor T cells can induce potent graft-versus-tumor (GVT)
      effects in hematologic malignancies and possibly solid tumors such as renal cell
      carcinoma. Two patients (27 and 30 years old) with metastatic melanoma received
      allogeneic PBSCT from an HLA-identical sibling donor after reduced conditioning
      with fludarabine, carmustine and melphalan. One patient showed a delayed mixed
      response with complete regression of lymph node metastases but persistent liver
      metastasis at day +60 and +120, consistent with a GVT response. In order to
      generate donor-derived tumor-reactive cytotoxic T lymphocytes (CTLs), peripheral
      blood mononuclear cells were stimulated with donor dendritic cells (DCs) loaded
      with host tumor lysate. Using these culture conditions, a marked increase in
      CD8(+) CTLs was observed in both donors exhibiting a strong MHC class I
      restricted cytotoxic activity against the host tumor without cross-reactivity
      against nonmalignant host cells. CDR3 spectratyping was used to analyze the
      complexity of T-cell subpopulations in both CTL lines. Results demonstrate that
      oligoclonal T cells are expanded in vitro, exhibiting a marked overexpression of
      TCRVbeta3 (donor 1) and TCRVbeta4/Vbeta11 (donor 2) subfamilies. Functional
      (ELISPOT assay) and phenotypic (CDR3 spectratyping, sequencing Vbeta transcripts)
      analysis of patients' T cells at different time points after transplantation
      demonstrated an expansion of alloreactive T cells with a limited TCR Vbeta
      pattern. The Vbeta3 cDNA clone, being predominant in the CTL line from donor 1,
      could not be identified in patient 1 peripheral blood lymphocytes after
      transplant. Altogether, our results provide the first evidence that GVT effects
      against melanoma can induce tumor regression and that oligoclonal donor-derived
      CTLs specific against host tumor cells can be generated in vitro that may be used
      for adoptive T-cell transfer after allogeneic transplantation.

PMID- 12209590
TI  - TP53 mutations in breast cancer tumors of patients from Rio de Janeiro, Brazil:
      association with risk factors and tumor characteristics.
AB  - Somatic mutations in the TP53 gene are the most frequently observed genetic
      alterations in human malignancies, including breast cancer, which is one of the
      leading causes of death among women in Brazil. In our study, we determined the
      frequency and the pattern of TP53 mutations in malignant breast tumors from 120
      patients living in Rio de Janeiro, Brazil. TP53 mutations were found in 20% of
      the tumors, which contained a diversity of mutation types: missense (62.5%),
      nonsense (8.3%), silent (4.2%), intronic (12.5%), insertion (4.2%) and deletion
      (8.3%). Of a total of 15 missense mutations, 4 were observed at Arg248 and 2 at
      Cys242, which are directly involved in DNA binding and in zinc binding,
      respectively. A subgroup of 51 patients was analyzed with respect to the relation
      between the presence of TP53 mutations and classical risk factors and with tumor
      and patient characteristics. For this analysis, we used logistic regression and,
      in order to obtain more precise confidence intervals, they were recalculated
      using a bootstrap resampling technique. Our results demonstrate that these
      mutations are not statistically associated with the risk factors or the patients'
      characteristics. However, the presence of TP53 mutations is strongly associated
      with the aggressiveness of the tumors, measured by Elston classification (OR =
      11.97 and 95% CI of 2.24-307.05). This finding is in agreement with previous
      studies, which report the presence of TP53 mutations in tumors with poor
      prognosis. This correlation between tumor aggressiveness and TP53 mutations could
      be a crucial variable for the treatment and prognosis of breast cancer.

PMID- 12209589
TI  - Inhibition of CD40 expression and CD40-mediated dendritic cell function by tumor
      derived IL-10.
AB  - As CD40 plays a key role in both antitumor immunity and DC maturation, we have
      studied the regulation of its expression during DC hematopoiesis (dendropoiesis)
      in vitro and in vivo in the tumor microenvironment. Using MC38 colon
      adenocarcinoma tumor models, we have demonstrated that DCs generated in vitro
      from bone marrow precursors obtained from tumor-bearers have significantly lower
      expression of CD40 molecules compared to DCs generated from tumor-free mice.
      Furthermore, CD40 expression on DCs isolated from the spleens of tumor-bearing
      mice was also significantly reduced, suggesting that tumor-derived factors
      inhibit CD40 expression on DCs during dendropoiesis both in vitro and in vivo.
      Interestingly, CD40 ligation on DCs generated from tumor-bearers did not result
      in inducible expression of IL-12 protein or IL-12 p40 mRNA. However,
      Staphylococcus aureus-induced IL-12 production by DCs was not altered in tumor
      bearers, confirming that inhibition of IL-12 production by DCs generated in vitro
      from tumor-bearing mice was due to reduced expression of CD40 on DCs. We have
      also shown that MC38 tumor cells produce IL-10 and that exogenous IL-10 causes
      downregulation of CD40 expression on DCs. In addition, endogenous IL-10 produced
      by colon carcinoma cells inhibited CD40-dependent IL-12 production by DCs since
      tumor-induced inhibition of IL-12 production was abrogated by neutralizing anti
      IL-10 antibody. Finally, systemic administration of FLT3L and/or CD40L reversed
      CD40 and IL-12 (p40) deficiency of DCs in tumor-bearing mice in vivo. These
      findings thus demonstrate that tumor-derived factors, including IL-10, inhibit
      CD40 expression on DCs and DC precursors and suppress their maturation and
      function.

PMID- 12209591
TI  - Recent thymic emigrants and prognosis in T- and B-cell childhood hematopoietic
      malignancies.
AB  - The concentration of T-cell receptor rearrangement excision DNA circles (TRECs)
      in peripheral blood mononuclear cells (PBMCs) is currently known to be a marker
      of recent thymic emigrants. We evaluated the hypothesis that TREC values would be
      lower in childhood T-cell hematopoietic malignancies than in childhood B-cell
      acute lymphoblastic leukemia (ALL) or healthy controls because the former
      category may reflect compromised thymic function. From the Greek national
      childhood leukemia/lymphoma database we obtained all 30 available T-cell
      leukemia/non-Hodgkin's lymphoma cases, 30 age- and sex-matched childhood B-cell
      origin cases of ALL and 60 healthy hospital controls. We compared TREC levels in
      PBMCs using a real-time PCR assay. There was highly significant reduction of TREC
      values in children with T-cell malignancies (median 3,100 TRECs/10(6) PBMCs),
      whereas children with B-cell origin ALL had slightly but nonsignificantly lower
      TREC values compared to healthy children (medians 19,300 and 22,500 TRECs/10(6)
      PBMCs, respectively). During a median follow-up period of about 19 months, only 4
      children died. All of them had a T-cell hematopoietic malignancy and relatively
      low TREC values. The number of TRECs was higher among healthy girls than among
      healthy boys, and a similar pattern was evident in T-cell malignancies. It
      appears that there is a pattern of concordance of high TREC values with better
      disease prognosis in hematologic childhood malignancies. This applies to specific
      disease entities with better prognosis (B-cell origin ALL having higher TREC
      values than T-cell leukemia/lymphoma) and to gender, another important predictor
      of prognosis conditional on disease entity (girls having higher TREC values than
      boys); however, it may also be true for the survival of individual patients.
      These preliminary findings can be used as hypothesis-generating indications that
      should be confirmed in larger data sets.

PMID- 12209592
TI  - Targeting of the photocytotoxic compound AlPcS4 to Hela cells by transferrin
      conjugated PEG-liposomes.
AB  - Photodynamic therapy has attracted increasing interest over the last few years,
      whereby the activation of photosensitizers by light causes the production of
      reactive oxygen species (ROS), such as singlet oxygen, which are cytotoxic. The
      goal of our study was to enhance the photodynamic activity of the photosensitizer
      aluminum phthalocyanine tetrasulfonate (AlPcS4) through its specific delivery to
      tumor cells. Since many tumor cells, among which are HeLa cells, overexpress the
      transferrin receptor, we synthesized transferrin conjugated PEG-liposomes that
      contained AlPcS4 that could be internalized by receptor mediated endocytosis. The
      antiproliferative activity of the targeted liposomes was evaluated and compared
      to the native AlPcS4 and the non-targeted liposome. These findings were
      supplemented with data on intracellular concentration of the photo-active
      compounds. The accumulation together with ROS production after irradiation was
      visualized by using confocal microscopy to confirm the data found in the
      antiproliferative and accumulation assay. Tf-Lip-AlPcS4 was 10 times more
      photocytotoxic (IC(50), 0.63 microM) than free AlPcS4 at a light dose of 45 kJ/m
      whereas Lip-AlPcS4 displayed no photocytotoxicity at all. The high
      photocytotoxicity of Tf-Lip-AlPcS4 was shown to be the result of a high
      intracellular concentration (136.5 microM) in HeLa cells, which could be lowered
      dramatically by incubating the conjugate with a competing transferrin
      concentration. The images of intracellular accumulation and ROS production
      matched the accumulation and photocytotoxicity profile of the different photo
      active compounds. The photodynamic activity of the Tf-Lip-AlPcS4 conjugate on
      HeLa cells is much more potent than free AlPcS4 as a result of selective
      transferrin receptor mediated uptake.

PMID- 12209593
TI  - Serum levels of angiogenin, basic fibroblast growth factor and endostatin in
      patients receiving intensive chemotherapy for acute myelogenous leukemia.
AB  - Angiogenesis seems to be important both in the pathogenesis of acute myelogenous
      leukemia (AML) and for the susceptibility of AML blasts to chemotherapy. Recent
      clinical studies even suggest that antiangiogenic therapy can induce disease
      control in patients with AML relapse. In this context we have investigated the
      profile of the systemic component of angiogenic regulation in AML by
      characterizing the serum levels of (i) the angiogenic regulators angiogenin,
      basic fibroblast growth factor (bFGF) and endostatin; (ii) the endothelial cell
      marker soluble (s) E-selectin. Patients with untreated AML had increased levels
      of angiogenin, endostatin and sE-selectin, whereas the levels of bFGF were not
      significantly altered. The systemic levels of the proangiogenic bFGF, the
      antiangiogenic endostatin and the endothelial cell marker sE-selectin showed
      significant correlations, whereas angiogenin and sE-selectin levels were not
      correlated. Furthermore, intensive chemotherapy resulted in decreased systemic
      levels of the 2 proangiogenic mediators angiogenin and bFGF, whereas endostatin
      levels remained high after treatment. Although angiogenin normally is a part of
      the acute phase reaction, its systemic levels were not altered when patients with
      chemotherapy-induced cytopenia developed complicating bacterial infections. Our
      results suggest that intensive chemotherapy can modulate the systemic component
      of angiogenic regulation in AML patients.

PMID- 12209594
TI  - Incidence and survival of squamous cell carcinoma of the tongue in Scandinavia,
      with special reference to young adults.
AB  - In several countries, increased incidence of squamous cell carcinoma (SCC) of the
      tongue in young adults has been suspected during the last decades. Some reports
      indicate a lower survival rate for young patients compared to older patients. In
      other reports, there has not been any considerable difference in survival when
      comparing young adults to older patients, whereas some authors have shown better
      survival for young adults. This disease is rare in young adults, and early
      reports were based on comparable small numbers and selected patients. Our aim was
      first to perform a population-based study to determine if an increased incidence
      in SCC of the tongue could be verified in a larger population comprising the
      Scandinavian countries Denmark, Finland, Sweden and Norway. A second aim was to
      determine survival rates for young adults compared to older patients. The
      material was based on the annual cancer incidence and survival reports from the
      Scandinavian cancer registries. The study period was 1960-1994. During that
      period, 5,024 SCCs of the tongue were reported. Of these, 276 (5.5%) were young
      adults (20-39 years). The incidence increased at all ages except for women 65-79
      years old. The increase was most pronounced in young adults: 0.06-0.32 for men
      and 0.03-0.19 for women, counted by 100,000 person-years. Relative survival was
      significantly better for young adults compared to older patients.

PMID- 12209595
TI  - Leukaemia and non-Hodgkin's lymphoma in children of Sellafield male radiation
      workers.

PMID- 12209598
TI  - Differential sensitivity to imatinib of 2 patients with metastatic sarcoma
      arising from dermatofibrosarcoma protuberans.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a rare superficial sarcoma usually
      affecting the trunk, with significant risk of local recurrence. It is
      characterized by the presence of ring chromosomes or chromosomal translocations
      fusing the promoter of the collagen gene COL1A1 to the platelet-derived growth
      factor beta-chain gene PDGFB, increasing the production of PDGF locally and
      promoting autocrine or paracrine tumor growth. Fewer than 5% of patients with
      DFSP develop metastatic sarcoma, with a poor subsequent prognosis. Imatinib (STI
      571) was developed as an inhibitor of the PDGF receptor tyrosine kinase and has
      proven clinical activity against chronic myelogenous leukemia (expressing bcr
      abl) and gastrointestinal stromal tumors (expressing c-kit). We describe 2
      patients with metastatic and unresectable metastases from DFSP treated with
      imatinib. After confirmation of negative CD117 status of 2 sarcomas arising from
      DFSP, patients were given imatinib 400 mg po qd and assessed at regular intervals
      for their tolerance and response to therapy. One patient had a transient
      response, then progressed rapidly and died of disease. Another patient showed a
      partial response to therapy after 2 months, with resolution of superior vena cava
      syndrome and shrinking of metastatic lung lesions. His response is ongoing after
      6 months of therapy. These clinical data confirm findings from models of DFSP and
      support the use of imatinib in the rare setting of metastatic DFSP. Imatinib may
      be useful for patients with locally advanced DFSP, when other options for local
      therapy are limited.

PMID- 12209599
TI  - Tumor necrosis factor-related, apoptosis-inducing ligand supports growth of mouse
      mastocytoma tumors by killing tumor-infiltrating macrophages.
AB  - TRAIL antisense transfected mastocytoma cells (R56VTas) injected into syngeneic
      DBA/2 mice demonstrate significantly delayed tumor growth compared to mock
      transfected cells (R56VTMo). TRAIL expression in R56VTas cells was successfully,
      albeit not completely, downregulated, as shown by Western blots, flow-cytometric
      analysis and functionally by loss of cytolytic activity against TRAIL-R-bearing
      target cells. Immunohistochemic and immunoblotting analyses of ex vivo tumors
      confirmed the lower expression of TRAIL by the antisense transfection compared to
      the mock transfection. Investigating the mechanism of the delayed tumor growth,
      it was found that neither T nor NK cells but activated macrophages infiltrated
      the tumors. The number of infiltrating macrophages was significantly lower in the
      mock transfected compared to the TRAIL antisense transfected tumor sections,
      indicating that TRAIL-expressing tumor cells may lyse macrophages. Indeed,
      activated macrophages proved to be sensitive to TRAIL-mediated apoptosis. This
      indicates that, although macrophages can infiltrate the mastocytoma R56VT, they
      are in part eliminated by TRAIL-expressing tumor cells, allowing the tumor to
      rapidly grow. Hence, downregulation of TRAIL allows more macrophages to survive
      and to better attack the tumor cells, slowing down tumor growth. In conclusion,
      TRAIL expressed on R56VT tumor cells can impair an important innate immune
      defense mechanism against tumors by eliminating effector macrophages.

PMID- 12209600
TI  - Steady state levels of transforming growth factor-beta1 and -beta2 mRNA and
      protein expression are elevated in colonic tumors in vivo irrespective of dietary
      lipids intervention.
AB  - Colonic tumors of human origin produce abundant transforming growth factor (TGF)
      beta suggesting that TGF-beta is critical to their growth. Dietary lipids
      regulate a number of growth factors including TGF-beta. Whether elevated TGF-beta
      levels are consistently expressed in colonic tumors irrespective of the
      environmental milieu in an in vivo model is not known and forms the main
      objective of the present study. Male F344 rats were injected with azoxymethane,
      10 weeks later, rats bearing preneoplastic lesions were fed a low fat (5% corn
      oil) diet and 3 high fat (5% corn oil with 18% corn oil, fish oil or beef tallow)
      diets for 16 weeks. Colonic tumors and mucosae were processed and assessed for
      TGF-beta status. TGF-beta1 and -beta2 mRNA levels were upregulated in colonic
      tumors more than in mucosae of all diet groups. Dietary lipids modulated TGF-beta
      mRNA in both tumors and mucosae, high corn and fish oil diets upregulated TGF
      beta1 significantly more than the low fat corn oil or high fat beef tallow diets.
      Immunohistochemical assessments of tissues with different biological features
      revealed that TGF-beta1 and -beta2 were elevated in tumors and in selected
      microscopic preneoplastic lesions compared to normal mucosae. This is the first
      in vivo study, documenting that developing colonic tumors acquire upregulated TGF
      beta phenotype even in the presence of lipid environments capable of
      differentially regulating TGF-beta in normal mucosae. Elevated expression of TGF
      beta in a selected subset of microscopic preneoplastic lesions suggests that TGF
      beta plays an important role on both early and late stages of colon
      carcinogenesis.

PMID- 12209601
TI  - Heregulin inhibits proliferation via ERKs and phosphatidyl-inositol 3-kinase
      activation but regulates urokinase plasminogen activator independently of these
      pathways in metastatic mammary tumor cells.
AB  - Heregulin (HRG) and type I receptor tyrosine kinase (RTK) expression was
      investigated in the highly invasive and metastatic LM3 cell line, our previously
      described model of metastasis for mammary cancer (Bal de Kier Joffe et al. [1986]
      Invasion Metastasis 6:302-12; Urtreger et al. [1997] Int J Oncol 11:489-96).
      Although LM3 cells do not express HRG, they exhibit high levels of ErbB-2 and
      ErbB-3 as well as moderate expression of ErbB-4. Addition of exogenous HRGbeta1
      resulted in inhibition of both proliferation and migration of LM3 cells. HRGbeta1
      was also able to decrease the activity of urokinase-type plasminogen activator
      (uPA) and matrix metalloproteinase 9 (MMP-9), 2 key enzymes in the invasion and
      metastatic cascade. HRGbeta1 treatment of LM3 cells induced tyrosine
      phosphorylation of ErbB-2, ErbB-3 and ErbB-4 as well as the formation of ErbB
      2/ErbB-3 and ErbB-2/ErbB-4 heterodimers. Assessment of the signaling pathways
      involved in HRGbeta1 action indicated that the addition of HRGbeta1 to LM3 cells
      resulted in activation of phosphatidylinositol 3- kinase (PI-3K) and in strong
      induction of the association of the p85 subunit of PI-3K with ErbB-3. HRGbeta1
      also caused the rapid activation of ERK1/ERK2 and Stat3 and Stat5 (signal
      transducers and activators of transcription [STAT]). This is the first
      demonstration of the ability of HRGbeta1 to activate STATs in mammary tumor
      cells. Blockage of PI-3K activity with its chemical inhibitor wortmannin, or of
      MEK1/ERKs activity with PD98059, resulted in suppression of the ability of
      HRGbeta1 to inhibit LM3 cell growth. Notwithstanding the suppression of these 2
      signaling pathways, HRGbeta1 still proved capable of inhibiting uPA activity.
      Therefore, our results provide evidence that signaling pathways involved in
      HRGbeta1-induced proliferation appear to be distinct from those involved in
      HRGbeta1 regulation of uPA, a protease that plays a pivotal role in invasion and
      metastasis.

PMID- 12209602
TI  - Expression of CD154 on renal cell carcinomas and effect on cell proliferation,
      motility and platelet-activating factor synthesis.
AB  - CD40 activation by CD154 may trigger diverse cellular responses, ranging from
      proliferation and differentiation to growth suppression and cell death, in normal
      and malignant cells. However, the pathophysiologic role of CD154 expressed by
      tumor cells remains unclear. We have investigated the expression of the CD40
      CD154 system in 24 primary cultures derived from renal cell carcinomas, its
      correlation with tumor stage and its potential functional significance. We found
      coexpression of CD40 and CD154 in most of the renal carcinoma cell lines. CD154,
      but not CD40 expression, significantly correlated with tumor stage. Moreover,
      renal carcinoma cell lines also released the soluble form of CD154 into the
      supernatant. CD40 engagement by CD154 did not affect apoptosis or survival. On
      the contrary, CD154 stimulated cell proliferation, motility and production of
      PAF, a phospholipid mediator of inflammation with angiogenic properties.
      Furthermore, the renal carcinoma cell lines expressed PAF-R. Blockade of PAF-R by
      WEB-2170, a PAF-R antagonist, abolished the CD154-dependent motility, indicating
      a role for PAF synthesized after CD154 stimulation in renal carcinoma cell
      motility. In conclusion, this study identifies new functional properties for
      CD154, which are potentially relevant for the growth and dissemination of renal
      carcinoma cells.

PMID- 12209603
TI  - Increased expression of a COOH-truncated nucleophosmin resulting from alternative
      splicing is associated with cellular resistance to ionizing radiation in HeLa
      cells.
AB  - We previously demonstrated that transfecting HeLa cells with the 24 kDa basic
      fibroblast growth factor-2 (FGF-2) isoform dramatically increased cell survival
      after irradiation. To investigate genes implicated in this radioresistance
      acquisition, we compared mRNA expression between radioresistant 24 kDa FGF-2
      expressing cells (HeLa 3A) and radiosensitive control HeLa PINA cells using the
      differential display technique. Of the 32 differentially expressed mRNAs, 1
      presented a significant homology with a known gene. This 378 bp fragment
      presented 100% identity with exon 11 and 12 of human nucleophosmin (NPM) but
      differed by including a part of intron 9 in its 5' end. The differential
      expression of this fragment was confirmed using an RNase protection assay. We
      then cloned the entire corresponding mRNA and showed that it contained all the
      exons of NPM plus intron 9, suggesting that it was a splicing product of the NPM
      gene. This variant encoded for a 35-amino acid truncated NPM (NPM2). NPM2
      expression was increased in HeLa 3A. To investigate NPM2's role in
      radioresistance acquisition, we transfected HeLa cells with NPM2 cDNA and
      analyzed survival after irradiation of the clones obtained. After transfection
      with NPM2, radiosensitive HeLa cells exhibited a dramatic increase in cell
      survival after irradiation. Taken together, our results demonstrate that
      expression of a COOH-truncated NPM form resulting from the alternative splicing
      of NPM mRNA is able to increase cell survival after irradiation and suggests that
      it might be involved in cellular response to ionizing radiation.

PMID- 12209604
TI  - Novel products of the HUD, HUC, NNP-1 and alpha-internexin genes identified by
      autologous antibody screening of a pediatric neuroblastoma library.
AB  - Autologous serological screening of a cDNA expression library (SEREX) derived
      from childhood neuroblastoma led to the identification of 10 different antigens,
      including 6 novel gene products. The novel antigen 018INX was derived from a
      small open reading frame in a region of alpha-internexin mRNA that was previously
      described as 3' untranslated region. 018INX thus represents a novel type of tumor
      antigen. Five novel gene products were derived from NNP-1 (NNP3) and Hu genes
      (HuC-L, HuD3, HuDY, HuD1pro(c)). As indicated by sequence analysis, these
      antigens were generated by alternative splicing and/or alternative promoter usage
      or allelic polymorphism. mRNA expression analyses revealed different tissue
      restrictions of novel compared to known HuD and NNP-1 transcripts in normal and
      malignant tissues. The expressions patterns of distinct transcripts indicated
      potential clinical meanings as diagnostic and/or prognostic tissue markers. When
      kinetics of serum antibody titres against SEREX-defined antigens were compared to
      tumor load over time in our patient with neuroblastoma, we found 100-fold
      increases of anti-Hu and anti-018INX antibody titres preceding the clinical
      diagnosis of recurrent tumor growth after 2 years. When sera of pediatric
      patients with cancer (30) and healthy controls (30) were tested for humoral
      responses to SEREX-defined neuroblastoma antigens, we detected antibodies against
      all known antigens and NNP3 with low frequencies and titres in control sera,
      while anti-018INX and anti-Hu antibodies were found in cancer patients only. Our
      findings indicate that SEREX-defined tumor antigens might provide novel tools for
      understanding and treatment of this aggressive childhood malignancy.

PMID- 12209605
TI  - Ethnic variation in kallikrein expression in nipple aspirate fluid.
AB  - Socioeconomic factors cannot entirely explain why black women have an earlier age
      of breast cancer onset and higher mortality rates, stage for stage, than whites.
      We and others have shown that prostate-specific antigen [PSA, also known as human
      kallikrein (hK) 3] is a marker of breast as well as prostate cancer, that hK2 and
      hK3 are highly homologous at the DNA and protein level and that the level of
      progesterone, which appears to upregulate hK3, is influenced by ethnicity. We
      hypothesized that nipple aspiration fluid (NAF) hK2 and hK3 levels are (i) lower
      in black than white women; (ii) independently associated with breast cancer;
      (iii) influenced by menopausal status; and (iv) in combination are more
      informative about whether a woman has breast cancer than either marker alone. NAF
      was assayed for hK2 and hK3, and the results were stratified by ethnicity,
      presence or absence of cancer and menopausal status. Statistical analysis was
      then performed. When stratified by ethnicity, hK2 (p = 0.003) and hK3 (p = 0.027)
      levels in blacks were lower than in whites. hK2 was lower in premenopausal black
      than in white subjects, regardless of cancer status. Overall, hK2, hK3 and the
      ratio hK2/hK3 were lower in subjects with breast cancer than in normal subjects.
      hK3 was lower in postmenopausal women with breast cancer, regardless of
      ethnicity. hK2 and hK3 levels were higher in pre- than in postmenopausal whites.
      Using logistic regression and considering hK2, hK3, hK2/hK3 and ethnicity, hK3
      was significantly associated with breast cancer in both pre- (p < 0.001) and
      postmenopausal women (p = 0.023). In conclusion, whereas hK2, hK3, hK2/hK3 and
      ethnicity are each significantly associated with breast cancer bivariately, after
      entering the strongest predictor, hK3, into a logistic regression model, no other
      variable accounted for additional variation, although this observation is
      preliminary due to the limited number of black subjects in the study.

PMID- 12209606
TI  - Single-nucleotide polymorphism in the E-cadherin gene promoter modifies the risk
      of prostate cancer.
AB  - E-cadherin plays a major role in intercellular adhesion, cell polarity and tissue
      architecture. We determined the relative risk of PCa associated with a previously
      reported C/A SNP at -160 bp relative to the transcription-start site of the E
      cadherin gene promoter. Eighty-two PCa patients and 188 controls were genotyped.
      Genotype and allele frequencies differed significantly among cases and controls.
      A-allele carriers had a higher relative risk of PCa (OR = 3.6, 95% CI 2.0-6.4)
      compared to C-only carriers. AC and AA genotypes had an increased risk of PCa (OR
      = 3.8, 95% CI 2.1-6.8 and OR = 1.7, 95% CI 0.4-6.6, respectively) compared to CC
      genotypes.

PMID- 12209607
TI  - PTEN expression is associated with prognosis for patients with advanced
      endometrial carcinoma undergoing postoperative chemotherapy.
AB  - The prognostic significance of PTEN expression in endometrial carcinoma has not
      been clear. We conducted the present study to clarify the relationship between
      PTEN expression and prognosis in advanced endometrial carcinoma. Of 784 patients
      with endometrial carcinoma who underwent primary treatment between 1985 and 2000
      at 5 institutions, 98 pure endometrioid carcinomas with retroperitoneal lymph
      node metastasis were provided for our study. PTEN expression was determined by
      immunohistochemic staining. Negative or mixed PTEN staining was observed in 64
      (65.3%) patients. The survival rate for PTEN-positive patients was significantly
      higher than that for PTEN-negative or -mixed patients. PTEN-staining status was
      not associated with patient age, International Federation of Gynecology and
      Obstetrics (FIGO) stage, myometrial invasion or histologic grade. Of the 98
      patients, 87 received radiation therapy (n = 25) or chemotherapy (n = 62) after
      surgery. PTEN expression did not relate to survival for patients receiving
      radiation therapy. In contrast, the survival rate for PTEN-positive cases was
      significantly higher than that for PTEN-negative or -mixed cases when patients
      underwent chemotherapy (62.4% vs. 11.8%). Subsequent multivariate analysis
      revealed that PTEN staining was an independent prognostic factor for patients
      undergoing chemotherapy. PTEN-positive staining was a significant prognostic
      indicator of favorable survival for patients with advanced endometrial carcinoma
      who underwent postoperative chemotherapy.

PMID- 12209608
TI  - Extremely potent, rapid and costimulation-independent cytotoxic T-cell response
      against lymphoma cells catalyzed by a single-chain bispecific antibody.
AB  - A recent study reported on an anti-CD19/anti-CD3 single-chain bispecific antibody
      (bscCD19xCD3) exhibiting high activity against human B lymphoma cell lines
      (Loffler et al., Blood 2000;95:2098-103). In the present study, we have explored
      in detail the in vitro efficacy, T-cell donor variability, binding
      characteristics, specificity, kinetics and interleukin-2 (IL-2) dependence of
      bscCD19xCD3. We found that a majority of human donor T cells tested (n = 86) gave
      half-maximal B-lymphoma cell lysis (ED(50)) within a range of 10-50 pg/ml
      bscCD19xCD3, corresponding to sub-picomolar concentrations of the bispecific
      antibody. Under identical experimental conditions, the anti-CD20 monoclonal
      antibody rituximab had an at least 100,000-fold lower in vitro efficacy. The
      extreme potency of bscCD19xCD3 was in sharp contrast to the relatively low
      affinity of the anti-CD3 and anti-CD19 single-chain Fv portions in K(D) ranges of
      10(-7) and 10(-9) M, respectively. Cell lysis by bscCD19xCD3 was predominantly
      mediated by the population of CD8/CD45RO-positive T cells. Both immortalized CD4-
      and CD8-positive human T-cell clones were highly active effector cells as well.
      Cell lysis by bscCD19xCD3 was rapid and specific. The respective parental
      monoclonal antibodies inhibited cell lysis and CD19-negative cells were not
      harmed by T cells in the presence of high amounts of bscCD19xCD3. The potent T
      cell stimulus IL-2 could not markedly augment the activity of bscCD19xCD3
      stimulated T cells. In conclusion, bscCD19xCD3 could redirect unstimulated
      cytotoxic T cells against CD19-positive cells in an unexpectedly potent, rapid
      and specific fashion.

PMID- 12209609
TI  - Risk of invasive cervical cancer associated with polymorphic HLA DR/DQ
      haplotypes.
AB  - The genes encoding human leukocyte antigens (HLA) have shown to be associated
      with cervical neoplasia. To obtain reliable data on HLA associations with
      cervical tumors, the study should be performed within a strictly defined cohort.
      To investigate the population attributable risk of cervical cancer associated
      with the HLA class II haplotypes DR15 and DQ6 (DQA1*0102 and DQB1*0602), we
      performed a nested case-control study of 85 women who developed invasive cervical
      cancer and 120 healthy women from a population-based cohort of Swedish women. The
      relative risks of cervical cancer among DR15 and DQ6-positive women were 3.73
      [confidence interval (CI): 1.8-7.4] and 4.33 (CI: 2.1-8.5), corresponding to
      population attributable proportions of 27.9% and 30.8%, respectively. A
      susceptibility locus in the HLA class II region is involved in a substantial
      fraction of the etiology of cervical cancer.

PMID- 12209611
TI  - Risk factors for lung cancer among nonsmoking women.
AB  - To evaluate risk factors for lung cancer in nonsmoking women, we used data of a
      case-control study conducted between 1991 and 1996 in Germany. A total of 234
      female histologically confirmed lung cancer patients and 535 population controls
      who had never smoked more than 400 cigarettes in their lifetime were personally
      interviewed with respect to occupation, exposure to environmental tobacco smoke
      (ETS), family history of cancer, prior physician-diagnosed lung diseases or
      cancer and diet. One-year radon measurements in the last dwelling were performed.
      Odds ratios (OR) adjusted for age and region and 95% confidence intervals (CI)
      were calculated via logistic regression. When cumulative duration of exposure to
      ETS in hours was considered, the OR for high compared to not or low ETS exposed
      women was 2.62 (CI:1.35-5.06) for occupational exposure and OR=1.67 (CI:0.86
      3.25) for spousal exposure, exhibiting a significant trend for ETS at work.
      Working more than 10 years in jobs or industries with known or suspected lung
      carcinogens was associated with OR=2.0 (CI:0.99-4.0). An elevated risk due to
      prior lung diseases was present for pneumonia (OR=1.6; CI:1.07-2.40) and
      tuberculosis (OR=1.6; CI:0.77-3.37). No significant increase in risk with
      increasing residential radon levels or with the presence of a family history of
      lung cancer was apparent. Protective effects were observed for high vs. low
      consumption of fresh vegetables (OR=0.5; CI:0.25-0.82) and cheese (OR=0.3,
      CI:0.21-0.55). ETS at work, occupational hazards and previous pneumonia may be
      risk factors for lung cancer in nonsmoking women, while a diet rich in fresh
      vegetables and cheese seems to be protective.

PMID- 12209610
TI  - Prognostic relevance of MAGE-A4 tumor antigen expression in transitional cell
      carcinoma of the urinary bladder: a tissue microarray study.
AB  - TAAs of the MAGE family are mostly studied as targets of specific immune
      responses. Their potential relevance as tumor markers has also been underlined.
      We used a MAb, 57B, recognizing MAGE-A4 protein in paraffin-embedded sections, to
      evaluate its expression in bladder cancers by employing TMA including 2,317
      samples from 1,849 patients. In 2,090/2,317 cases (90.2%), immunostaining yielded
      interpretable results. Since for some patients more than 1 sample was available,
      only interpretable first biopsies (n = 1,628) were considered. MAGE-A4 protein
      was expressed at significantly (p < 0.001) higher frequency in squamous (25/55,
      45.5%) than in adeno (4/15, 26.7%), sarcomatoid (4/14, 28.6%), small cell (5/20,
      25%) or transitional cell (281/1,522, 18.5%) carcinomas. In TCCs, overall MAGE-A4
      positivity was significantly correlated with invasive phenotype (p < 0.001) and
      high tumor grade (p < 0.0001). Clinical data from 908 TCC patients were
      retrospectively evaluated, revealing that strong 57B staining was highly
      significantly associated with decreased tumor-specific survival (p < 0.0001).
      These data suggest that evaluation of MAGE-A4 protein expression is useful in the
      identification of groups of TCCs characterized by severe prognosis, thus possibly
      providing indications for early MAGE TAA-targeted immunotherapy.

PMID- 12209612
TI  - Is the telomerase assay useful for screening of endometrial lesions?
AB  - Telomerase activation is specifically observed in most cancers but not in normal
      tissues with some exceptions, such as germ cells or certain tissues with
      regenerative potential, suggesting a diagnostic opportunity for cancers involving
      measurement of telomerase activity. Cytologic screening for endometrial cancer
      has not been well established, due to the complexity of diagnostic criterion. In
      the present study, we investigated the utility of the telomerase assay for
      screening endometrial lesions. A total of 100 patients with or without
      endometrial lesions were examined for telomerase activity by the telomeric repeat
      amplification protocol (TRAP) assay using endometrial scraping samples and the
      correlation with cytology was investigated. The TRAP assay revealed frequent
      telomerase activation in normal endometria at reproductive age, particularly in
      67% of proliferative-phase endometria, suggesting that the telomerase assay is
      not suitable for screening women of reproductive age. However, in postmenopausal
      women, telomerase activity was rarely detected (8%) in normal endometria, while
      it was observed in >80% of endometrial cancers or hyperplasias. Interestingly,
      some cases of endometrial cancer and hyperplasia were misdiagnosed by cytology
      but correctly detected by the TRAP assay. The sensitivity of the TRAP assay to
      screen endometrial lesions was 87%, equivalent to that of cytology. Combination
      of cytology and the TRAP assay increased sensitivity to 100%. We thus concluded
      that measuring telomerase activity in endometrial scrapings is a useful
      diagnostic tool for the screening of endometrial lesions in postmenopausal women,
      particularly when used with cytology to increase screening sensitivity.

PMID- 12209613
TI  - Value of tenascin-C content and association with clinicopathological parameters
      in uterine cervical lesions.
AB  - To determine whether the content of the matrix protein tenascin-C (Tn-C) is of
      diagnostic or prognostic value in cervical lesions, we evaluated increases in Tn
      C immunoreactivity in 80 formalin-fixed, paraffin-embedded biopsies and surgical
      specimens of the uterine cervix. Tn-C content in the basement membrane zone and
      in the stroma was graded and compared to some prognostic parameters. In the
      normal cervix, Tn-C formed a thin continuous band. In cervicitis, Tn-C bands
      thickened in the basement membrane zone and the adjacent stroma in the form of
      thin filaments. In 30 squamous intraepithelial lesions (SILs) of various grades,
      Tn-C bands were either slightly (1+) or moderately (2+) thickened in the basement
      membrane zone, while slight stromal Tn-C immunoreactivity in the form of thin
      bands was observed in 12 cases, regardless of grade and inflammatory stromal
      reaction. In invasive carcinoma, Tn-C content was markedly increased in the
      stroma and around the invasive nests of tumors. The intensity of Tn-C
      immunoreactivity was significantly higher in grade I tumors than in others (p <
      0.04). The intensity of increase in Tn-C immunoreactivity was 10.5-fold (95% CI
      3.39-32.5) higher in invasive cervical carcinomas than in others (cervicitis, low
      grade SIL and high-grade SIL) (p = 0.0001). A significant correlation was found
      between weak Tn-C immunoreactivity and lymphatic space invasion (p = 0.001),
      lymph node metastasis (p = 0.01), desmoplastic stromal component (p = 0.0001) and
      stromal inflammation (p = 0.002). In conclusion, increase in Tn-C
      immunoreactivity may be of value in the assessment of noninvasive and invasive
      cervical lesions and the appearance of Tn-C may be an indicator of adequate
      biologic defense in cervical cancer patients.

PMID- 12209614
TI  - Cigarette smoking and breast cancer risk: a long latency period?
AB  - The association between cigarette smoking and breast cancer risk remains unclear.
      Few studies have examined cigarette smoking of very long duration as there may
      not have been a sufficient number of long-term smokers in studies conducted
      before the 1980s. Therefore, we examined the association between smoking and
      breast cancer risk using data from participants in a randomized controlled trial
      of screening for breast cancer involving 89,835 women aged 40-59 years at
      recruitment and with up to 40 years of smoking duration at that time. Women with
      breast cancer diagnosed through 31 December 1993 were identified by linkage to
      the Canadian Cancer Database. Cox proportional hazards models were used to
      estimate rate ratios (RRs) and 95% confidence intervals (CIs). During an average
      of 10.6 years of follow-up, we observed 2,552 incident cases of breast cancer. We
      found a positive association between cigarette smoking and breast cancer risk,
      driven mainly by women who had smoked for several decades and who, therefore, had
      commenced smoking many years earlier. Relative to never-smokers, women who had
      smoked 40 years or more and 20 cigarettes/day or more were at the highest risk
      (RR = 1.83, 95% CI 1.29-2.61); for women who had commenced smoking 40 years or
      more before assessment (a measure of smoking latency rather than duration and
      intensity), the RR was 1.22 (95% CI 0.99-1.59). Our findings suggest that smoking
      of very long duration and high intensity may be associated with increased risk of
      breast cancer.

PMID- 12209615
TI  - Human papillomavirus genotype prevalence in high-grade squamous intraepithelial
      lesions and colposcopically normal women from Zimbabwe.

PMID- 12209621
TI  - CTLA-4 engagement regulates NF-kappaB activation in vivo.
AB  - CTLA-4 engagement inhibits TCR-dependent functions and CTLA-4(-/-) mice develop a
      lymphoproliferative disorder leading to early lethality. In vitro, ligation of
      CTLA-4 reduces TCR-mediated activation of NF-kappaB, a transcription factor
      implicated in promoting T cell survival and cytokine production. However, whether
      NF-kappaB inhibition downstream of CTLA-4 is necessary for down-regulation of T
      cell responses is not known. We hypothesized that signaling pathways that are
      antagonized when CTLA-4 is engaged should be augmented when CTLA-4 is absent and
      found thatspontaneous NF-kappaB activity was increased in T cells from CTLA-4(-/
      ) mice. To determine the importance of NF-kappaB inhibition upon CTLA-4
      engagement in vivo, CTLA-4(-/-) mice were interbred with mice expressing a
      transdominant IkappaBalpha mutant under the control of the Lck promoter. The
      resulting mice had reduced spontaneous NF-kappaB activity in T cells,delayed
      mortality, and reduced leukocytic accumulation in spleen, lymph nodes, and
      exocrine pancreas as compared with CTLA-4(-/-) littermates. However, impaired NF
      kappaB activation in T cells did not prevent the up-regulation of activation
      markers on T cells or the acquisition of effector cytokine production. Thus,
      impaired NF-kappaB activity in T cells prevents specific aspects of the CTLA-4(-/
      ) phenotype, suggesting that inhibition of NF-kappaB activation is one of the key
      biochemical events regulated by CTLA-4 ligation in vivo.

PMID- 12209622
TI  - Peptide analysis, stability studies, and structural modeling explain
      contradictory peptide motifs and unique properties of the NOD mouse MHC class II
      molecule H2-A(g7).
AB  - The MHC class II molecule H2-A(g7) is the chief genetic determinant in insulin
      dependent diabetes mellitus of the non-obese diabetic (NOD) mice. Poor peptide
      binding ability, as well as presentation of a unique subset of peptides by this
      molecule was suggested to promote autoimmunity in this strain. However, several
      laboratories have presented results in favor of an H2-A(g7) molecule that can
      avidly bind many different peptides. The crystal structures of H2-A(g7) in
      complex with two different peptides did not completely resolve this issue. To
      analyze the peptide binding capacity and the motif requirements of H2-A(g7), we
      eluted natural ligands from purified H2-A(g7) molecules isolated from the H2
      A(g7)-transfected M12-C3 cells. A low peptide yield dominated by a few peptide
      ligands was found. Pool sequencing and alignment of individual ligands on the
      basis of molecular modeling revealed a peptide-binding motif with
      basic/aliphatic/small hydrophilic amino acids at relative position 1 (p1),
      aliphatic amino acids at p4, Ala at p6, and acidic amino acids and Ser/Gly at p9,
      as well as acidic residues at p10/11. Though weak, the binding of individual
      ligands, as well as the importance of an acidic C-terminal residue was confirmed
      by peptide binding studies to isolated H2-A(g7) molecules. Furthermore, the H2
      A(g7) molecule incompletely dissociated into its constituent chains in SDS
      electrophoresis under nonreducing conditions. This provides additional evidence
      of its weak affinity for peptides, which probably arises from the combination of
      beta56His/beta57Ser/beta78Ala and other unique H2-A(g7) residues in contact with
      the antigenic peptide. These results allow a better understanding of the role of
      this molecule in the development of autoimmunity and the identification of
      epitopes relevant to diabetes.

PMID- 12209623
TI  - Virus clearance and immunopathology by CD8(+) T cells during infection with
      respiratory syncytial virus are mediated by IFN-gamma.
AB  - CD8(+) T cells (CTL) are important effector cells for virus control and
      immunopathology after primary infection with respiratory syncytial virus (RSV).
      To investigate the effector mechanisms involved, we set up an adoptive transfer
      model, in which effector CTL specific for p82-90 of RSV M2 were generated in
      vivo, followed by short-term restimulation in vitro and transfusion into infected
      recipients. A total of 4 x 10(4) donor-derived p82-specific CTL homing to the
      lung within 4 days after transfusion were sufficient to completely eliminate a
      virusinoculum of 1.5 x 10(6) pfu. This was accompanied by significant lung
      pathology. Surprisingly, virus control and immunopathology proceeded unimpaired
      when donor cells lacking perforin, CD95 ligand or TNF were transfused. By
      contrast, treatment of recipient mice with a neutralizing antibody against IFN
      gamma or transfusion of IFN-gamma-deficient effector CTL largely abolished virus
      control and significantly reduced CD8(+) T cell-mediated pathology. In IFN-gamma
      deficient mice, high-dose primary infection experiments revealed attenuated
      immunopathology, but only slightly delayedvirus clearance, suggesting that other
      cells and molecules can partly substitute for the effects of CTL-derived IFN
      gamma on virus clearance. These experiments identify IFN-gamma as a key molecule
      in RSV-induced immunopathology and in CD8(+) T cell-mediated control of RSV
      infection.

PMID- 12209624
TI  - A non-peptide CCR5 antagonist inhibits collagen-induced arthritis by modulating T
      cell migration without affecting anti-collagen T cell responses.
AB  - The chemokine receptors CCR5 and CXCR3 have been implicated as playing a central
      role in directing a Th1 inflammatory response. Here, we investigated whether a
      synthetic CCR5 antagonist affects the process of T cell migration to sites of
      inflammation. Immunization of DBA/1 mice with type II collagen resulted in
      typical arthritis, which is associated with cellular infiltration. Treatment with
      a CCR5 antagonist strikingly affected the development of arthritis by reducing
      both incidence and severity of disease. There was no substantial difference
      between collagen-immunized mice with and without antagonist treatment in the
      induction of anti-collagen T cell responses and the capacity to produce IL-12.
      This endogenous IL-12 functioned to induce comparable levels of CCR5 in these two
      immunized groups of T cells. Whereas a massive infiltration of inflammatory cells
      including CCR5(+) T cells occurred in the joints of mice immunized without
      antagonist, cellular infiltration in the antagonist-treated group was only
      marginal. These results indicate that administration of a CCR5 antagonist
      inhibits the development of arthritis not by affecting the generation of collagen
      sensitized T cells but by interfering with their migration to joint lesions.

PMID- 12209625
TI  - Functional expression of the lymphoid chemokines CCL19 (ELC) and CCL 21 (SLC) at
      the blood-brain barrier suggests their involvement in G-protein-dependent
      lymphocyte recruitment into the central nervous system during experimental
      autoimmune encephalomyelitis.
AB  - Migration of autoaggressive T cells across the blood-brain barrier (BBB) is
      critically involved in the initiation of experimental autoimmune
      encephalomyelitis (EAE), an animal model for multiple sclerosis. The direct
      involvement of chemokines in this process was suggested by our recent observation
      that G-protein-mediated signaling is required to promote adhesion strengthening
      of encephalitogenic T cells on BBB endothelium in vivo. To search for chemokines
      present at the BBB, we performed in situ hybridizations and immunohistochemistry
      and found expression of the lymphoid chemokines CCL19/ELC and CCL21/SLC in
      venules surrounded by inflammatory cells. Their expression was paralleled by the
      presence of their common receptor CCR7 in inflammatory cells in brain and spinal
      cord sections of mice afflicted with EAE. Encephalitogenic T cells showed surface
      expression of CCR7 and the alternative receptor for CCL21, CXCR3. They
      specifically chemotaxed towards both CCL19 or CCL21 in a concentration dependent
      and pertussis toxin-sensitive manner comparable to naive lymphocytes in vitro.
      Binding assays on frozen sections of EAE brains demonstrated a functional
      involvement of CCL19 and CCL21 in adhesion strengthening of encephalitogenic T
      lymphocytes to inflamed venules in the brain. Taken together our data suggest
      that the lymphoid chemokines CCL19 and CCL21 besides regulating lymphocyte homing
      to secondary lymphoid tissue are involved in T lymphocyte migration into the
      immunoprivileged central nervous system during immunosurveillance and chronic
      inflammation.

PMID- 12209626
TI  - Evidence for an early appearance of modern post-switch immunoglobulin isotypes in
      mammalian evolution (II); cloning of IgE, IgG1 and IgG2 from a monotreme, the
      duck-billed platypus, Ornithorhynchus anatinus.
AB  - To trace the emergence of the modern post-switch immunoglobulin (Ig) isotypes in
      vertebrate evolution we have studied Ig expression in mammals distantly related
      to eutherians. We here present an analysis of the Ig expression in an egg-laying
      mammal, a monotreme, the duck-billed platypus (Ornithorhynchus anatinus).
      Fragments of platypus IgG and IgE cDNA were obtained by a PCR-based screening
      using degenerate primers. The fragments obtained were used as probes to isolate
      full-length cDNA clones of three platypus post-switch isotypes, IgG1, IgG2, and
      IgE. Comparative amino acid sequence analysis against IgY, IgE and IgG from
      various animal species revealed that platypus IgE and IgG form branches that are
      clearly separated from those of their eutherian (placental) counterparts.
      However, the platypus IgE and IgG still conform to the general structure
      displayed by the respective Ig isotypes of eutherian and marsupial mammals.
      According to our findings, all of the major evolutionary changes in the
      expression array and basic Ig structure that have occurred since the evolutionary
      separation of mammals from the early reptile lineages, occurred prior to the
      separation of monotremes from marsupial and placental mammals. Hence, our results
      indicate that the modern post-switch isotypes appeared very early in the
      mammalian lineage, possibly already 310-330 million years ago.

PMID- 12209627
TI  - Conversion of grass pollen allergen-specific human IgE into a protective IgG(1)
      antibody.
AB  - More than 100 million individuals exhibit IgE-mediated allergic reactions against
      Phl p 2, a major allergen from timothy grass pollen. We isolated cDNA coding for
      three Phl p 2-specific human IgE antibodies from a combinatorial library, which
      was constructed from lymphocytes of a grass pollen-allergic patient. Recombinant
      Phl p 2-specific IgE antibody fragments (Fab) recognized a fragment comprising
      the 64 N-terminal amino acids of Phl p 2 and cross-reacted with group 2 allergens
      from seven grass species. cDNA coding for the variable regions of one of the IgE
      Fab were cloned into aplasmid vector expressing the constant region of human
      IgG(1) to obtain a complete, recombinant Phl p 2-specific human IgG(1). This
      antibody blocked the binding of grass pollen-allergic patients IgE (n=26; mean
      inhibition: 58%) to Phl p 2 and caused a 100-fold reduction of Phl p 2-induced
      basophil histamine release. The recombinant human Phl p 2-specific IgG(1) may be
      used for environmental allergen detection, for standardization of diagnostic as
      well as therapeutic grass pollen allergen preparations and for passive therapy of
      grass pollen allergy.

PMID- 12209628
TI  - Gelatinase B deficiency protects against endotoxin shock.
AB  - Gelatinase B or matrix metalloproteinase-9 (MMP-9) is stored in the tertiary
      granules of polymorphonuclear leukocytes. These cells are key effectors in acute
      inflammatory diseases such as sepsis. Endotoxin leads to rapid release of
      gelatinase B from these granules in vitro and in vivo, but the role of this
      enzyme in bacterial sepsis and endotoxin shock remains unclear. We studied the
      clinical course of endotoxinemia and its relation with the expression of
      gelatinase B from the pool of circulating leukocytes in adult as well as in young
      mice in a model of endotoxin-induced shock and compared wild-type with gelatinase
      B-deficient mice. The gelatinase B-deficient mice were resistant to endotoxin
      shock, which implies that specific MMP-9 inhibition constitutes anapproach for
      the treatment of septic shock syndromes.

PMID- 12209629
TI  - Mutational analysis and molecular modeling of the binding of Staphylococcus
      aureus enterotoxin C2 to a murine T cell receptor Vbeta10 chain.
AB  - We investigated the role of the beta chain HV4 region in the binding of a Vbeta10
      T cell receptor to superantigen S. aureus enterotoxin C2 (SEC2)/MHC class II
      complexes. Residues 6971 of the Cw3/1.1 TCR Vbeta10 chain, derived from an H
      2K(d)-restricted cytotoxic clone, were individually changed to alanine using site
      directed mutagenesis, and mutated TCR beta chains were transfected along with the
      wild-type TCR alpha chain into a TCR alpha(-)beta(-) T hybridoma. SEC2/MHC
      recognition was measured by IL-2 production. Alanine substitutions in the HV4beta
      region, either did not affect (Ser69 and Lys71), or increased the recognition of
      SEC2/HLA-DR1 complex (Asp70), arguing against a general and direct role for the
      HV4beta region in superantigenrecognition. A theoretical-computational model of
      the SEC2/TCR Vbeta10 chain complex was constructed and predicted the presence of
      a unique salt bridge between Vbeta Asp30 and SEC2 Lys103. A perfect correlation
      was found between the likely presence of this salt bridge and the capacity of the
      HV4beta and previously obtained CDR1beta alanine mutants to induce an equal or
      greater response than the wild-type TCR.

PMID- 12209630
TI  - Evidence for preferred MHC class II-TCR recognition independent of the source of
      bound peptide.
AB  - The interaction between TCR and peptide-MHC is well described in terms of the
      recognition of the peptide, but the recognition of the MHC is less well
      understood. At issue is whether particular V gene products may have higher
      affinity for some MHC over others and to what extent the bound peptide influences
      V gene selection. We examined this issue by developing T cell lines in which the
      presenting MHC class II molecule has a constant TCR contact region, while the
      presented peptides vary. If there is an affinity between particular V genes and
      the specific MHC used, only a subset of the V genes will be associated with the
      response. Indeed, in all the cell lines analyzed, there was a reproducible usage
      of a limited number of Vbeta genes, regardless of the bound peptides. This Vbeta
      gene constraint was independent of the CDR3 sequence, compatible with the lack of
      involvement of specific peptides. Our results support the hypothesis that certain
      V gene products may have a preference for interacting with a particular MHC
      molecule, and this could have an impact in selectively controlling immune
      responses.

PMID- 12209631
TI  - Lipid rafts as the signaling scaffold for NK cell activation: tyrosine
      phosphorylation and association of LAT with phosphatidylinositol 3-kinase and
      phospholipase C-gamma following CD2 stimulation.
AB  - Natural killer (NK) cells participate in both innate and adaptive immunity
      through the prompt secretion of cytokines and ability to lyse virally infected
      cells or tumor cells. Although it has been well understood that lipid rafts
      (rafts) and a raft-associated linker for activation of T cells (LAT) plays a
      central role in TCR signal transduction, there are still great gaps in our
      knowledge of the molecular events involved in NK cell activation. We show here
      that CD2 and rafts became polarized to the site of NK cell activation by CD2
      cross-linking or target cell binding using confocal microscopy, and LAT and a
      significant amount of CD2 colocalized in raft fractions of sucrose-density
      gradient from an NK cell line, NK3.3. CD2 cross-linking strongly induced tyrosine
      phosphorylation of LAT, resulting in increased association with
      phosphatidylinositol 3-kinase (PI 3-K) and phospholipase C-gamma1 (PLC-gamma1).
      In vitro binding studies using glutathione S-transferase fusion proteins
      demonstrated that a large portion of the association between LAT and PI 3-K or
      PLC-gamma1 was mediated through their SH2 domains in tyrosine phosphorylation
      dependent manner. Furthermore, disruption of lipid rafts by cholesterol depletion
      from cell membranes using methyl-beta-cyclodextrin markedly reduced LAT tyrosine
      phosphorylation and NK cell functions, including cytotoxicity and granule
      exocytosis. These results document that modulation of raft integrity by
      aggregation of NK cell activating receptors, which leads to the formation of
      complexes of LAT with PI 3-K and PLC-gamma1, is essential for the NK cell lytic
      mechanisms.

PMID- 12209632
TI  - CD8 lethargy in the absence of CD4 help.
AB  - CD4 T cell help was proposed to have a pivotal role in orienting CD8 T cell
      responses to antigen stimulation. By activating antigen-presenting cells (APC),
      CD4 cells would induce their expression of costimulatory molecules, the "signal
      two" required to induce full CD8 activation, preventing CD8 tolerance. Recent
      data on this subject is contradictory, as the absence of help did not always
      result in CD8 tolerance. These differences were attributed either to the presence
      of residual CD4 help or, respectively to the type of antigen stimulation, the
      peptide affinity, the CTL frequencies, and/or the strength of the response. We
      therefore reassessed the role of CD4 help in CD8 responses using a system where
      CD4 cells are absent and APC not activated. This system can be manipulated to
      induce CD8 tolerance (at high antigen concentrations) or CD8 memory (at low
      antigen concentrations). We found that the presence of CD4 help did not prevent
      tolerance induction. On the other hand, the absence of CD4 help did not induce
      CD8 tolerance, but rather led to differentiation stage intermediate between
      naive/memory/tolerant cells that we call "lethargy". These findings indicate that
      role of CD4 help in CD8 responses does not follow a simple on-off rule, as
      previously suggested. They also reveal that the "tolerance versus memory"
      dichotomy fails to account for all possible states/properties of antigen
      experienced CD8 cells. Depending on the priming conditions, other intermediate
      stages of differentiation may occur.

PMID- 12209633
TI  - Proteasome inhibition leads to NF-kappaB-independent IL-8 transactivation in
      human endothelial cells through induction of AP-1.
AB  - IL-8 is an important mediator of leukocyte trafficking and activation,
      participating in tumor angiogenesis, inflammatory processes and coronary
      atherosclerosis. Under flow conditions IL-8, in conjunction with MCP-1, triggers
      the firm adhesion of monocytes to the vascular endothelium. While previous
      studies have suggested the requirement of NF-kappaB for IL-8 secretion by
      endothelial cells, we investigated the possibility of IL-8 transactivation under
      conditions of NF-kappaB suppression. Inhibition of the proteasome by MG-132 or
      lactacystin completely blocked TNF-alpha-induced IkappaBalpha degradation as well
      as NF-kappaB activity in human arterial endothelial cells. Surprisingly, basal
      secretion of IL-8 protein was eight- to tenfold induced by proteasome inhibitors,
      while MCP-1 expression was, as expected, completely down-regulated. IL-8 was up
      regulated at the transcriptional level, and promoter studies proved a more than
      ninefold induction of transcription factor AP-1 activity to be the cause of
      increased IL-8 transcription. Mutation of the AP-1 binding site in an IL-8
      promoter construct completely abrogated this effect, while mutation of the NF
      kappaB motif did not influence IL-8 transactivation by proteasome inhibitors.
      With DNA binding assays we found a seven- to eightfold induction of
      phosphorylated c-Jun and hence JNK kinase activity under MG-132 treatment.
      Induction of JNK kinase appeared independent of the cell type, even in tumor cell
      lines not responding to proteasome inhibitors. Since neither inactivation of p53
      in wild-type p53 cells nor reintroduction of functional p53 into p53(-/-) cells
      affected MG-132-inducible IL-8 secretion, a direct influence of p53 on IL-8
      regulation could be excluded. These results show that proteasome inhibitors can
      not only lead to functional AP-1 induction by enhanced c-Jun phosphorylation, but
      also transactivate the IL-8 gene in human endothelial cells despite complete
      suppression of NF-kappaB activity.

PMID- 12209634
TI  - Protection of marmoset monkeys against EAE by treatment with a murine antibody
      blocking CD40 (mu5D12).
AB  - CD40-CD40 ligand interactions are crucial to cognate interactions between T
      cells, B cells and antigen-presenting cells (APC), and contribute to non-antigen
      specific effector functions of APC in inflammatory disorders. Here we demonstrate
      that functional blockade of CD40 with an antagonist mouse anti-human CD40
      monoclonal antibody (mAb mu5D12) effectively prevents clinical expression of
      chronic demyelinating experimental autoimmune encephalomyelitis (EAE) in outbred
      marmoset monkeys, a preclinical model of multiple sclerosis. Anti-CD40 mAb
      interfered with development of clinical symptoms of marmoset EAE during the
      treatment period, even when treatment was started several weeks after T cell
      priming. Magnetic resonance imaging demonstrated inflammatory activity in the
      brain at initiation of antibody treatment, confirming that treatment interfered
      with the disease process. Access of therapeutic anti-CD40 to potential sites of
      action, the secondary lymphoid organs and the brain white matter lesions, was
      visualized in situ. The present data are the first to demonstrate the clinical
      potential of blocking APC and effector cell functions using murine antagonist
      anti-CD40 mAb in the treatment of chronic inflammatory diseases.

PMID- 12209635
TI  - Role of IgM antibodies versus B cells in influenza virus-specific immunity.
AB  - We have compared the role of IgM antibodies with the role of B cells in control
      of primary influenza virus infection. Mice deficient in IgM (IgM(-/-)), but
      capable of producing other Igisotypes, exhibited increased pulmonary virus titers
      compared to wild-type mice. However, IgM(-/-) mice were less susceptible compared
      to B cell-deficient micro MT) mice. CD4(+) T cells from spleen and lung draining
      lymph nodes of infected micro MT mice showed reduced proliferation upon virus re
      stimulation in vitro. Furthermore, numbers of IFN-gamma-producing CD4(+) effector
      T cells were reduced in the alveolar lavage (BAL) of micro MT mice but not IgM(-/
      ) mice. In contrast, total number of virus-specific CTL was almost comparable in
      BAL of micro MT and wild-type mice. Pulmonary recruitment of inflammatory
      macrophages and neutrophils occurred normally in both micro MT and IgM(-/-) mice.
      Interestingly, virus-specific IgG2a and IgG2b antibody responses were affected
      locally in the BAL and in the serum of IgM(-/-) mice, while IgG1 responses
      remained largely normal. Taken together, our data suggest a role for B cells to
      promote effector T cell responses and a role of both IgM and IgG antibodies in
      the defense against acute influenza virus infection.

PMID- 12209636
TI  - Growth and expansion of human T regulatory type 1 cells are independent from TCR
      activation but require exogenous cytokines.
AB  - Cloned T regulatory type 1 (Tr1) cells produce IL-10, TGF-beta, IFN-gamma, and
      very low or non-detectable levels of IL-2 and IL-4, following TCR-mediated
      activation. In addition, upon TCR stimulation, Tr1 cell clones up-regulate
      activation markers but show low proliferative responses, partially due to the
      suppressive effect of autocrine IL-10 and TGF-beta. Here we show that Tr1 cells
      have growth requirements different from those of Th1 and Th2 cells. Exogenous IL
      15, and to a lesser extent IL-2, induce and support the proliferation of Tr1
      cells in the absence of TCR activation. This strong cytokine response correlates
      with high constitutive levels of the IL-2/15Rbeta and common gamma chains
      expressed by Tr1 cell clones. Furthermore, suboptimal doses of IL-15, in
      combination with IL-2, induce a significant growth (median value: 25-fold
      increase in cell number) of Tr1 cell clones during a culture period of 11 days,
      which leads to an in vitro expansion of Tr1 cell clones comparable to that of Th1
      and Th2 cell clones. Tr1 cell clones cultured in IL-15 continue to secrete
      immunosuppressive cytokines and to proliferate poorly upon reactivation via TCR.
      These findings indicate that Tr1 cells are constitutively capable of responding
      to cytokines and mainly to IL-15. This growth factor enables a significant in
      vitro expansion of Tr1 cells facilitating further biological and biochemical
      characterization of this unique T cell subset.

PMID- 12209637
TI  - Characterization of the in vivo function of TNF-alpha-related apoptosis-inducing
      ligand, TRAIL/Apo2L, using TRAIL/Apo2L gene-deficient mice.
AB  - To define the normal physiological role for the TRAIL/Apo2L in vivo, we generated
      TRAIL/Apo2L gene-targeted mice. These mice develop normally and show no defects
      in lymphoid or myeloid cell homeostasis or function. Although TRAIL/Apo2L kills
      transformed cells in vitro, TRAIL/Apo2L(-/-) mice do not spontaneously develop
      overt tumors at an early age. However, in the A20 B cell lymphoma-transferred
      tumor model, TRAIL/Apo2L(-/-) mice are clearly more susceptible to death from
      overwhelming tumor burden, due to increased lymphoma load in the liver. A20
      tumors are susceptible to TRAIL/Apo2L killing in vitro, indicating that
      TRAIL/Apo2L may act directly to control A20 cells in vivo. Despite the fact that
      TRAIL binds osteoprotegerin and osteoprotegerin-transgenic mice are
      osteopetrotic, TRAIL/Apo2L(-/-) mice show no evidence of altered gross bone
      density, and no alterations in frequency or in vitro differentiation of bone
      marrow precursor osteoclasts. Moreover, leucine zipper TRAIL has no toxicity when
      repeatedly administered to osteoprotegerin(-/-) mice. Thus, TRAIL/Apo2L is
      important in controlling tumors in vivo, but is not an essential regulator of
      osteoprotegerin-mediated biology, under normal physiological conditions.

PMID- 12209638
TI  - Phenotypic analysis of the murine CD4-related glycoprotein, CD223 (LAG-3).
AB  - CD223 (LAG-3) is an activation-induced cell surface molecule, structurally
      similar to the T cell coreceptor CD4, that binds MHC class II molecules with high
      affinity. Little is known about the expression and function of murine CD223.
      Here, we show that mRNA expression is restricted to the thymic medulla, splenic
      red pulp and sparse cells in the adult brain cortex. In contrast, surprisingly
      high expression was seen in defined tracts at the base of the cerebellum and in
      the choroid plexus of day 7 postnatal brain. mCD223:Ig, but not CD4:Ig, fusion
      proteins stained cells expressing MHC class II molecules. Analysis of mCD223 cell
      surface expression was performed with a new monoclonal antibody (mAb) that
      recognizes an epitope in the D2 domain. Although it blocked mCD223 function in
      vitro, it did not block binding of mCD223 to MHC class II molecules. While very
      few TCRalpha beta T cells in the spleen and thymus of naive mice express surface
      mCD223 (<3 %), approximately 18 % TCR gamma delta T cells and approximately 10 %
      NK cells are positive. This small population of TCRalpha beta T cells are cycling
      memory T cells (BrdU(+), CD44(hi), CD62L(lo)). In contrast, all T cells express
      mCD223 2-3 days post activation. This study and the anti-CD223 mAb should greatly
      assist in the elucidation of CD223 function.

PMID- 12209639
TI  - Receptor editing in CD45-deficient immature B cells.
AB  - B cell receptor signaling threshold regulates negative selection of autoreactive
      B cells and determines the mechanism of B cell tolerance. Using mice carrying
      immunoglobulin transgene specific for MHC class I antigen K(k) (3-83 Tg mice),
      and IL-7-driven bone marrow (BM) culture system, we have previously shown that
      receptor editing is a major mechanism in B cell tolerance. To test the role of
      BCR signaling competence on the induction of tolerance-mediated receptor editing,
      we crossed the 3-83 Tg mice with mice deficient in CD45, a protein tyrosine
      phosphatase that functions asa positive regulator of the BCR signaling. We found
      that in the absence of self-antigen allelic exclusion is efficiently imposed in 3
      83 Tg CD45(-/-) mice, although numbers of peripheral B cells are reduced. Using
      our BM culture system, we show here that immature 3-83 Tg CD45(-/-) B cells
      encountering self-antigen are developmentally arrested and undergo secondary
      light chain recombination and receptor editing, not different than CD45
      sufficient cells. Thus, lack of CD45 does not abolish the receptor editing
      competence in immature B cells encountering high avidity membrane-bound antigen.

PMID- 12209640
TI  - Systemic immune responses induced by mucosal administration of lipopeptides
      without adjuvant.
AB  - We recently reported that parenteral injection of malaria palmitoyl-tailed
      peptides without adjuvant efficiently induces B, Th and CTL responses. We now
      show that intranasal (IN) or sub-lingual (SL) delivery of such lipopeptides
      induces strong systemic immune responses, as demonstrated by specific Th cell
      responses from the spleen as well as inguinal lymph nodes, and by the production
      ofhigh levels of serum antibodies. Overall, both types of responses were
      significantly higher than in parallel experiments in which the same lipopeptides
      were delivered by the subcutaneous (s.c.) route. Moreover, the mucosal route
      resulted in the preferential induction of IFN-gamma producing T cells and of
      IgG2a antibody production, as compared to the dominant IL-4 and IgG1 responses
      obtained by the s.c. route, thus bringing a distinct advantage in the field of
      many infectious diseases and allergy. Possibly related to this Th1 response, we
      found that dendritic cells, the principal immune-competent cells to encounter
      antigens within mucosal membranes, take up lipopeptide antigens more efficiently
      than macrophages. Mucosal immunization by lipidated peptides appears therefore as
      a novel, noninvasive vaccine approach that does not require the use of extraneous
      adjuvant and which, besides cost-effectiveness, has attractive practical and
      immunological features.

PMID- 12209642
TI  - Combinatorial peptide library-based identification of peptide ligands for tumor
      reactive cytolytic T lymphocytes of unknown specificity.
AB  - A novel approach for the identification of tumor antigen-derived sequences
      recognized by CD8(+) cytolytic T lymphocytes (CTL) consists in using synthetic
      combinatorial peptide libraries. Here we have screened a library composed of 3.1
      x 10(11) nonapeptides arranged in a positional scanning format, in a cytotoxicity
      assay, to search the antigen recognized by melanoma-reactive CTL of unknown
      specificity. The results of this analysis enabled the identification of several
      optimal peptide ligands, as most of the individual nonapeptides deduced from the
      primary screening were efficiently recognized by the CTL. The results of the
      library screening were also analyzed with a mathematical approach based on a
      model of independent and additive contribution of individual amino acids to
      antigen recognition. This biometrical data analysis enabled the retrieval, in
      public databases, of the native antigenic peptide SSX-2(41-49), whose sequence is
      highly homologous to the ones deduced from the library screening, among the ones
      with the highest stimulatory score. These results underline the high predictive
      value of positional scanning synthetic combinatorial peptide library analysis and
      encourage its use for the identification of CTL ligands.

PMID- 12209641
TI  - MHC class II isotype-specific signaling complex on human B cells.
AB  - The highly polymorphic human major histocompatibility complex (HLA) class II
      molecules are acknowledged as signaling receptors although their coupling to
      signaling pathways is not yet fully elucidated. In this study, we investigated
      how HLA class II can be coupled to protein tyrosine kinase (PTK) signaling
      pathway in B cells and whether there might be differences depending on HLA class
      II isotype. Using the human B cell line Ramos, we demonstrate that CD19 and CD20
      are two HLA class II-associated receptors that couple HLA class II to PTK
      signaling pathway where CD20 appears to be amajor component of HLA class II
      mediated activation of Src kinases. Both HLA-DR and HLA-DP co-immunoprecipitate
      tyrosine-phosphorylated proteins (p-Tyr) whereas only activation through HLA-DR
      increases the tyrosine phosphorylation of these proteins. Indeed, in contrast to
      HLA-DR, cross-linking HLA-DP induces neither tyrosine phosphorylation nor
      homotypic adhesion, and induces ERK1/2 activation. Differential association of
      these isotypes with CD20 appears to be one of the mechanisms underlying their
      differential signaling. We provide an experimental evidence for a mechanism by
      which HLA class II molecules can be coupled to PTK signaling pathway and,
      underscores their isotypes differential signaling. Further investigation of these
      mechanisms is likely to provide new insights into how isotype specific MHC class
      II signaling can contribute to the regulation of the immune response.

PMID- 12209643
TI  - Vaccination with recoverin, a cancer-associated retinopathy antigen, induces
      autoimmune retinal dysfunction and tumor cell regression in mice.
AB  - Recoverin (Rec)-specific CTL present in peripheral blood recognize Rec-expressing
      tumor cells of patients with cancer-associated retinopathy (CAR), a
      paraneoplastic retinopathy syndrome. To evaluate the effects of Rec on retina and
      cancer cells, we generated an experimental mouse model, tested the induction of
      Rec-specific anti-tumor CTL, and analyzed retinal function using
      electroretinogram (ERG) in these animals. We observed a Rec-specific CTL response
      in BALB/c mice and significant growth inhibition of Rec-expressing syngeneic
      MethA fibrosarcoma cells in vivo. R64 (AYAQHVFRSF) peptide, derived from Rec that
      induces anti-tumor CTL in humans, produced anti-tumor effects in BALB/c mice.
      Furthermore, elevated anti-Rec antibodies correlated with decreased ERG
      amplitudes in Rec, Rec-expressing tumor and R64-treated mice. These data suggest
      that Rec contains amino acid sequences which cause retinal dysfunction, but they
      also induce anti-tumor CTL and tumor regression. These observations describe
      initial characterization of the CAR mouse model, a necessary step in developing
      new insight into immunological mechanisms of paraneoplastic syndromes and tumor
      immunity for potential immunotherapeutic approaches to cancer.

PMID- 12209644
TI  - Cultured human intestinal mast cells express functional IL-3 receptors and
      respond to IL-3 by enhancing growth and IgE receptor-dependent mediator release.
AB  - Mast cells are immunoregulatory effector cells capable of releasing different
      mediators and cytokines implicated in inflammatory tissue processes. Previous
      studies suggested that IL-3 regulates growth and function of murine mast cells
      and human mast cell precursors, but does not affect mature human mast cells. In
      the present study, we found expression of IL-3 receptors (IL-3R) in freshly
      isolated human intestinal mast cells by reverse transcriptase (RT)-PCR and in
      mast cells cultured with stem cell factor (SCF) using RT-PCR and flow cytometry.
      IL-3R expression was enhanced when the culture medium was supplemented with IL-4
      in addition to SCF. In the presence of SCF, IL-3 significantly enhanced mast cell
      growth in a dose-dependent fashion (179+/-51% of control, p</=0.004, n=9, ED(50)
      approximately 15 ng/ml) by decreasing mast cell apoptosis rather than inducing
      proliferation. Furthermore, IL-3 selectively enhanced histamine (from 39.6+/-12.4
      to 51.2+/-15.7% specific release, p<0.02, n=8) and leukotriene C(4) (LTC(4),
      5.1+/-3.4 to 10.8+/-5.5 ng/10(6) mast cells, p<0.03, n=6) release triggered by
      IgE receptor cross-linking without affecting prostaglandin D(2) production. In
      conclusion, our data show that human intestinal mast cells express functional IL
      3R, indicating that IL-3 not only regulates growth and function of immature, but
      also that of mature human mast cells.

PMID- 12209646
TI  - Synergistic roles of IgM and complement in antigen trapping and follicular
      localization.
AB  - We have investigated the roles of IgM and complement (C) in the enhancement of
      primary immune responses and the localization of protein antigen (Ag) in the
      spleen. Pentameric but not monomeric IgM enhances antibody (Ab) responses in both
      wild-type and secretory micro-deficient (micro(s) (-/-)) mice, indicating that a
      single IgM clone is sufficient as long as it activates C. Ag localizes on
      follicular dendritic cells (FDC) within 16 h after injection of immune complexes
      (IC) containing pentameric but not monomeric IgM. Surprisingly, pentameric IgM
      containing IC were trapped in spleens of C3-depleted and Cr2-deficient mice.
      However, the IC were found only in the marginal zone (MZ), associated
      predominantly with MZ macrophages. IC were also detected in the MZ in normal mice
      within 1 h after injection, but associated with other cells in addition to MZ
      macrophages. The results demonstrate an important role for pentameric IgM in the
      initiation of Ag trapping, a step independent of C3 activation and of the
      interaction of IC with CR1 and CR2. The data also provide direct evidence that C3
      activation is required for the next phase of localization, in which Ag moves from
      the MZ to FDC, with consequent enhancement of specific immune responses.

PMID- 12209645
TI  - Strong antigenic selection shaping the immunoglobulin heavy chain repertoire of B
      1a lymphocytes in lambda 2(315) transgenic mice.
AB  - The B lymphocyte compartment of the recombinant mouse line L2 consists
      predominantly of CD5(+) B-1 cells that exclusively express the transgenic (Tg)
      lambda 2 L chain of the plasmacytoma MOPC315. Using such Tg mice as a simplified
      model to study positive selection processes, we show that restriction to a single
      L chain results in a strongly oligoclonal IgH chain repertoire in fetal and
      neonatal liver-derived B cells, as well as in peritoneal CD5(+) B-1 lymphocytes
      from adult mice. In contrast, in vitro differentiated fetal liver Pro/PreB-I
      cells from L2 embryos show a clear increase of complementarity determining region
      three (CDR3) diversity. These data suggest that the antibody repertoire of B-1a
      cells is strongly selected by antigen during fetal as well as adult peritoneal
      phase.

PMID- 12209647
TI  - Availability of antigen-presenting cells can determine the extent of CD4 effector
      expansion and priming for secretion of Th2 cytokines in vivo.
AB  - Like dendritic cells (DC), activated B cells are effective antigen-presenting
      cells (APC) for naive CD4 cells due to their expression of MHC class II and
      multiple costimulatory molecules. We showed previously that CD4 cells primed in B
      cell-deficient micro MT) mice undergo more limited expansion than in normal
      animals after immunization with keyhole limpet hemocyanin. Here we report that in
      the absence of B cells, priming of effectors with the capacity to produce the Th2
      cytokines, IL-4, IL-5 and IL-13, was profoundly reduced whereas the development
      of effectors that secrete the Th1 cytokine IFN-gamma was much less affected. A
      blockade of IL-12 reduced priming of IFN-gamma-secreting effectors but did not
      reverse the IL-4, IL-5, or IL-13 deficiency of the response. CD4 cell expansion
      and priming for Th2 cytokines in micro MT mice was reconstituted by adoptive
      transfer of activated splenic B cells, which were present throughout the primary
      response. However, transfer of splenic DC from either control or micro MT mice
      also supported development of Th2 cytokine responses, indicating that an APC
      deficit rather than a unique contribution of B cells accounted for diminished
      effector priming. We conclude that CD4 cell expansion must be sustained via APC
      for the development of Th2 cytokine-secreting effectors in vivo and that in
      responses to protein antigen, B cells can be a crucial population to serve in
      this role. The results suggest that the level of APC engagement can not only
      determine the extent of effector expansion, but also the overall Th1/Th2 cytokine
      balance.

PMID- 12209648
TI  - Lack of antigen-specific immune responses in anti-IL-7 receptor alpha chain
      antibody-treated Peyer's patch-null mice following intestinal immunization with
      microencapsulated antigen.
AB  - Peyer's patches (PP) represent a well-characterized inductive site in gut
      associated lymphoid tissue that actively acquires antigens from the intestinal
      lumen. It was reported that organized PP are not required for antigen-specific
      IgA responses induced by oral immunization with soluble antigen mixed with the
      mucosal adjuvant, cholera toxin. However, the role of PP in the induction of
      mucosal and systemic immune responses remains to be clarified in the case of
      particulate antigen. Here, we created PP-null mice by treating them with
      monoclonal anti-IL-7 receptor alpha chain (IL-7 R alpha) antibody during
      gestation and then immunized with antigen-encapsulated poly-lactic acid (PLA)
      microspheres. Brisk OVA-specific antibody responses were noted in serum and fecal
      extracts of normal mice following direct intestinal immunization with OVA in PBS
      (OVA-PBS) as well as in PLA-microspheres (OVA-MS). Antibody production was
      similarly elevated in PP-null mice immunized with OVA-PBS via direct injection
      into the intestinal tract. In contrast, OVA-specific antibody responses were
      dramatically decreased in both serum and fecal extracts collected from PP-null
      mice immunized intestinally with OVA-MS. These results were further supported by
      the number of OVA-specific antibody-forming cells detected in the spleen and
      intestinal lamina propria. PP deficiency also resulted in the reduction in OVA
      specific Th1/Th2 cell responses in the spleen and mesenteric lymph nodes of mice
      intestinally immunized with OVA-MS. These results suggested that organized PP do,
      in fact, play a crucial role in the induction of antigen-specific immune
      responses against ingested particulate antigen.

PMID- 12209649
TI  - CpG-DNA aided cross-presentation of soluble antigens by dendritic cells.
AB  - For cross-presentation immature dendritic cells (DC) require enhanced antigen
      (Ag) uptake and a maturation signal to prime for MHC class I-restricted CTL
      responses in vivo. While immunostimulatory CpG-DNA provides, via TLR9, the
      maturation signal, CpG-DNA linked to Ag augments cellular Ag uptake. In this
      study we show that CpG-DNA ovalbumin (OVA) conjugates trigger in vivo peptide
      specific CTL responses at tenfold lower Ag doses compared to a mixture of CpG-DNA
      plus OVA. We provide evidence that CpG-DNA-OVA conjugates shift OVA uptake by
      immature DC from the presumably inefficient fluid phase pinocytosis to efficient
      DNA receptor-mediated endocytosis. Since the DNA-binding receptor mediating
      endocytosis lacks any sequence specificity, cellular uptake of OVA conjugated
      with either stimulatory or non-stimulatory oligonucleotides (ODN) is equally
      enhanced. As a consequence cross-linking of OVA with either stimulatory or non
      stimulatory DNA yields, via enhanced OVA uptake, efficient generation and
      presentation of the dominant OVA-CTL epitope SIINFEKL. However, only stimulatory
      CpG-ODN cross-linked to OVA provide the DC maturation signal required to trigger
      robust primary CTL responses towards the cross-presented MHC class I complexed T
      cell epitope SIINFEKL. Our studies show that stimulatory CpG-ODN linked to Ag
      fulfill a dual role: enhancement of Ag uptake yielding efficient Ag cross
      presentation by DC and in addition, their activation into professional DC.

PMID- 12209650
TI  - CD4+CD25+ T cells as immunoregulatory T cells in vitro.
AB  - We have further characterized the in vitro phenotype and function of anergic and
      suppressive CD4(+)25(+) T cells. Following TCR ligation, DO.11.10 CD4(+)25(+) T
      cells suppress the activation of OT-1 CD8(+)25(-) T cells in an antigen
      nonspecific manner. Although suppression was seen when using a mixture of APC
      from both parental strains, it was very much more marked when using F1 APC. APC
      pretreated with, and then separated from CD4(+)25(+) T cells did not have
      diminished T cell costimulatory function, suggesting that APC are not the direct
      targets of CD4(+)25(+) T cell regulation. CTLA-4 blockade failed to abrogate
      suppression by CD4(+)25(+) T cells in mixing experiments. Although CD4(+)25(+) T
      cells failed to respond following cross-linking of TCR, they could be induced to
      proliferate following the addition of exogenous IL-2, allowing the generation of
      a T cell line from CD4(+)25(+) T cells. After the first in vitro restimulation,
      CD4(+)25(+) T cells were still anergic and suppressive following TCR engagement.
      However, after three rounds of restimulation, their anergic and suppressive
      status was abrogated.

PMID- 12209651
TI  - Differential sensitivity of Jurkat and primary T cells to caspase-independent
      cell death triggered upon Fas stimulation.
AB  - Fas-induced apoptosis, a key event in the regulation of lymphocyte homeostasis,
      is mainly mediated by the activation of a cascade of caspases. Using caspase- and
      Fas-associated death domain protein-deficient Jurkat cell lines as well as a pan
      caspase inhibitor (Z-VAD-fmk), we observed a second Fas-induced cell death event,
      independent of any known caspase activation. This pathway is of slow kinetics and
      displays some features of necrosis. However, this caspase-independent pathway
      does not seem to play a significant role in the Fas-mediated death of primary
      activated T cell blasts. Indeed, in this setting, Fas-induced cell death was
      always substantially inhibited by Z-VAD-fmk, suggesting that caspase activation
      is an absolute requirement in the Fas-induced death of primary human T
      lymphocytes.

PMID- 12209652
TI  - Mercaptoacetate decreases latency to initiate independent ingestion, but not
      suckling, in preweanling rats.
AB  - Altering oxidation of fatty acids by administration of mercaptoacetate (MA) or
      methyl palmoxirate has been demonstrated to stimulate independent ingestion in
      rat pups by 12 to 15 days of age. However, in other work, neither agent has been
      demonstrated to affect intake in the context of suckling. In the present
      experiments, we tested the effects of MA on both suckling and independent
      ingestive behavior by examining changes in latency to initiate suckling or
      independent ingestion and by measuring intake in short-term (30 min) and longer
      term (4 hr) suckling and independent ingestion tests in pups aged 12 to 15 days
      of age. The results demonstrated that (a) MA does not affect suckling intake in
      short- or longer term tests; (b) MA does not affect latency to attach to a
      nipple, most likely due to floor effects on latency to attach in control pups;
      (c) MA stimulates independent ingestion in short-term, but not longer terms
      tests; and (d) MA reduces the latency to initiate independent ingestion. These
      results suggest that administration of MA preferentially stimulates the
      initiation of independent ingestion over suckling, and that this response
      develops at an age just prior to the time at which independent ingestion is
      typically first expressed by rat pups.

PMID- 12209653
TI  - Effects of prenatal sensory stimulation on heart rate and behavioral measures of
      arousal in bobwhite quail embryos.
AB  - Although a number of studies have demonstrated the effects of altered prenatal
      experience on subsequent behavioral development, how these effects are achieved
      remains a topic of enduring interest. The present study examined the immediate
      effects of unimodal and multimodal prenatal sensory stimulation on physiological
      and behavioral arousal in bobwhite quail embryos. Embryos were videotaped and
      their heart rate was monitored during a 4-min exposure period to (a) no
      supplemental sensory stimulation, (b) unimodal auditory stimulation, (c) unimodal
      visual stimulation, (d) two sources of concurrent auditory stimulation, or (e)
      concurrent auditory/visual stimulation. Results indicated that quail embryos'
      overall activity levels and heart rate can be significantly affected by the type
      of prenatal sensory stimulation provided during the period prior to hatching. In
      particular, multimodal stimulation increased both behavioral activity levels and
      heart rate compared to controls. Across the unimodal and intramodal groups,
      however, behavioral and physiological measures revealed different patterns of
      activity in response to supplemental sensory stimulation, highlighting the value
      of using multiple levels of analysis in exploring arousal mechanisms involved in
      prenatal perceptual responsiveness.

PMID- 12209654
TI  - Subchronic methylphenidate administration has no effect on locomotion, emotional
      behavior, or water maze learning in prepubertal mice.
AB  - Methylphenidate hydrochloride (Ritalin, MPH) is frequently prescribed as a
      treatment for children with attention deficit hyperactivity disorder (ADHD), yet
      little research has been conducted to determine its potential long-term
      neurobehavioral effects. We assessed the effects of subchronic MPH administration
      (2.5, 5, 10, 20, 40, or 80 mg/kg) on male CD-1 mice treated from 26 to 32 days of
      age. When tested at 33 days of age in the open field and elevated plus maze,
      there were no significant differences in spontaneous locomotion, exploration, or
      fear- and anxiety-related behaviors. Testing from 34 to 37 days of age in a water
      maze task revealed no significant effects of any dose of MPH on learning in this
      simple paradigm. While it is difficult to extrapolate directly from these results
      to clinical effects in humans, our results indicate that preexposure of mice to
      MPH late in the postnatal developmental period does not appear to alter later
      behavior. We are currently conducting additional studies to further probe the
      potential effects of MPH administration during development and to examine various
      contributing factors including stage of development, duration of MPH
      administration, complexity of the task used to assess behavioral changes, and
      type of cognitive process being analyzed (attention, nonspatial working memory,
      etc.).

PMID- 12209655
TI  - Physiological arousal in females with fragile X or Turner syndrome.
AB  - Physiological arousal was measured in 12- to 22-year-old females with either
      fragile X, Turner syndrome, or neither disorder to explore potential differences
      in the manifestation of arousal and anxiety in adolescents and young women.
      Physiological arousal was measured at baseline and during performance on mental
      arithmetic, divided attention, and risk-taking tasks. Contrary to prediction,
      females with fragile X rarely exhibited higher arousal than females in either the
      Turner syndrome or comparison groups. On the Divided Attention Task, both the
      fragile X and Turner syndrome groups exhibited higher arousal relative to one
      another based on different physiological indices. Relative to the comparison
      group, the fragile X group presented with a heightened state of arousal at
      baseline, based on mean skin conductance range, which may account for little
      increase in arousal on the cognitive tasks for females with fragile X. Females
      with Turner syndrome exhibited higher arousal relative to the comparison group on
      all cognitive tasks, but not for all physiological measures. Factors potentially
      associated with heightened arousal in fragile X and Turner syndrome are
      discussed.

PMID- 12209656
TI  - Relative right versus left frontal EEG in neonates.
AB  - Although infants have been noted to have greater relative right or left frontal
      EEG as early as the neonatal period, other ways in which these newborns differ
      have not been reported. In this study, 48 newborns were divided on the basis of
      greater relative right versus greater relative left frontal EEG to determine
      whether these groups differed in other ways at the neonatal period including
      behavior, physiology, and biochemistry. We also were interested in whether these
      EEG patterns were related to any prenatal maternal variables including mood
      states (depression, anxiety, anger) and biochemistry as well as fetal activity.
      The greater relative right frontal EEG newborns had mothers with lower prenatal
      and postnatal serotonin and higher postnatal cortisol levels. The mothers of the
      greater relative right frontal EEG newborns also had greater relative right
      frontal EEG activation and lower vagal tone. The greater relative right frontal
      EEG newborns themselves had elevated cortisol levels, showed a greater number of
      state changes during sleep/wake behavior observations, and performed less
      optimally on the Brazelton Neonatal Behavior Assessment (T. B. Brazelton, 1973)
      including the habituation, motor, range of state, excitability, and depressive
      symptoms scales. These data suggest that greater relative right frontal EEG
      newborns may be at greater risk for developmental problems than those with
      greater relative left frontal EEG activation. In addition, a discriminant
      function analysis correctly classified 67% of the newborns' EEGs by prenatal
      maternal variables, suggesting that these might be used to target pregnant women
      for prenatal intervention.

PMID- 12209657
TI  - An exploratory study of fetal behavior at 33 and 36 weeks gestational age in
      hypertensive women.
AB  - The relationship between maternal blood pressure (BP) and fetal behaviors as well
      as differential spontaneous and vibroacoustic elicited fetal behaviors were
      examined in hypertensive (n = 21) compared to normotensive (n = 22) women at 33
      and 36 weeks gestational age (GA). Maternal BP was negatively related to GA at
      birth and birth weight. On average, fetuses of hypertensive women were born 2
      weeks earlier (38 weeks GA) and 340 g lighter. Maternal systolic BP was
      negatively related to the number of spontaneous body movements observed on
      ultrasound scan over 20 min and the magnitude of the fetal heart rate (FHR)
      acceleration elicited by a vibroacoustic stimulus. At 36 weeks GA, vibroacoustic
      stimulation elicited differential responding with fetuses in the hypertensive
      compared to the normotensive group having fewer body movements, a lower magnitude
      of FHR acceleration, and a lack of cardiac-body movement coupled responses. These
      findings suggest a relationship between maternal BP and fetal behaviors and
      differential functional development of sensory-motor response systems which need
      to be characterized in the subgroups of hypertensive disorders observed during
      pregnancy.

PMID- 12209658
TI  - EEG asymmetry, power, and temperament in children.
AB  - Measures of EEG spectral power, lateral asymmetry in the frontal and parietal
      areas, and social behavior with an examiner were analyzed on 166 children, 10 to
      12 years old, who were participating in a longitudinal study of the temperamental
      contributions to social behavior. Loss of 8- to 13-Hz power (alpha band) on the
      right, compared with the left, frontal area (right frontal active) was most
      prevalent among children who were classified as high reactive at 4 months and
      were highly fearful at 14 and 21 months. Second, greater frontal power in the 14-
      to 30-Hz band (beta) at rest was correlated with the tendency to be right frontal
      active. Finally, spontaneous talkativeness with an unfamiliar examiner was
      associated with right frontal activation and high alpha power for boys, but with
      right frontal activation and high beta power for girls. Right frontal activation
      is most characteristic of children who begin life with a temperamental bias
      favoring high reactivity and who develop a fearful reaction to unfamiliar events
      in the second year of life.

PMID- 12209659
TI  - Prenatal disturbance alters the size of the corpus callosum in young monkeys.
AB  - Many factors during fetal life and early infancy have been found to affect the
      development of the brain. The following study investigated whether maternal
      stress during pregnancy would influence the size and shape of one sensitive brain
      region, the corpus callosum, in infant monkeys. For 30% of the gestation period,
      from Days 90 to 140 postconception, gravid females were disturbed using an
      acoustical startle protocol for 10 min per day. Magnetic resonance imaging was
      then employed to obtain sagittal and coronal scans of their infants' brains.
      Morphometric measures of the corpus callosum were compared in 16 monkeys (5
      controls and 11 from disturbed pregnancies). Prenatal conditions altered the
      corpus callosum, but in a differential manner for male and female monkeys. Based
      on the midsagittal and parasagittal scans, prenatally disturbed male offspring
      showed a decrease in overall size of the corpus callosum whereas the prenatal
      disturbance resulted in an increased area in females. An evaluation of callosal
      height from the coronal images suggested that the volumetric change was
      associated with a shift in anterior-to-posterior shape from the genu back toward
      the splenium. These findings concur with observations in other animals and
      humans, which have indicated that prenatal and postnatal factors can influence
      the development of the corpus callosum, possibly affecting communication between
      the hemispheres.

PMID- 12209660
TI  - Screening for cervical disease in mature women: strategies for improvement.
AB  - BACKGROUND: Cervical carcinoma remains a significant health risk for the older
      woman. In the current study the yield of screening of mature women in an
      established, opportunistic screening program was examined. Strategies for
      improving screening in this age group were identified through examination of
      recent Pap test history of women with high grade squamous intra-epithelial
      lesions (HSIL). METHODS: From the population based registry of the Ontario
      Cervical Screening Program, the Pap test cytodiagnoses for almost 700,000 women
      screened during the first six months of 2000 were classified by age quintile.
      Screening yields for younger women (< 50 years of age) and mature women (>/= 50
      years of age) were compared using the detection ratio (abnormalities per 1000
      women tested). Any pap test results during the three years preceding a diagnosis
      of HSIL in mature women were identified (excluding any Pap test in the six months
      immediately prior to the HSIL cytodiagnosis) and classified into one of three
      categories: no prior test known, prior negative Pap test known, and prior
      abnormal Pap test known. RESULTS: Twenty four percent of all Pap tests in the six
      month period were from mature women. Approximately 11% of all cytodiagnoses of
      HSIL and carcinoma (HSIL+), and 13% of all low grade squamous intra-epithelial
      lesions (LSIL), HSIL, carcinoma, and atypical glandular cells of uncertain
      significance (AGUS); [LSIL+ and AGUS] cytodiagnoses, were from mature women. The
      yield of Pap testing in mature women (1.7 HSIL+ per 1000 women tested) was
      slightly more than 40% of that for younger women (4.2 HSIL+ per 1000 women
      tested). Mature women with HSIL were more likely to have had a history of no
      prior screening (61.1%) than younger women (49.5%). The majority (62.9%) of
      mature women with HSIL and a prior known Pap test had a prior registered abnormal
      Pap test. CONCLUSIONS: Pap testing of mature women yields a significant number of
      abnormalities, but is less efficient than Pap testing of younger women. Screening
      yield could be increased by recruiting mature women who are currently
      inadequately screened and by revising guidelines for cessation of screening.
      Proper followup of mature women with Pap test abnormalities would improve
      clinical outcome but could adversely affect the yield of Pap testing, since
      current inappropriate repeat testing of women would decrease.

PMID- 12209661
TI  - Diagnostic value, feasibility, and validity of preparing cell blocks from fluid
      based gynecologic cytology specimens.
AB  - BACKGROUND: The current study was conducted to investigate the diagnostic value,
      feasibility, and validity of preparing cell blocks from fluid-based gynecologic
      cytology methods. METHODS: The authors independently reviewed 125 cell blocks
      prepared from material remaining after the ThinPrep smear was diagnosed, with a
      concentration on those cases demonstrating abnormal results. RESULTS: The
      majority of cases were easy to diagnose on hematoxylin and eosin stained
      sections. The addition of a cell block preparation increased the detection of an
      endocervical cell component compared with the use of ThinPrep alone. Of the 125
      cell blocks studied, 15 were interpreted as high-grade squamous intraepithelial
      lesions, 70 were interpreted as low-grade SILs, 24 were interpreted as atypical
      squamous cells of undetermined significance, and 16 were determined to be within
      normal limits. Eighty-six of the cell blocks (69%) were found to be in agreement
      with the ThinPrep diagnosis, 29 (23%) demonstrated a lesser degree of abnormality
      on the cell block compared with the ThinPrep slide, and 10 (8%) demonstrated
      changes that were more severe than those diagnosed on the corresponding ThinPrep
      slide. Of the 54 cases for which histopathologic follow-up was available (e.g.,
      punch biopsy, cone biopsy, or hysterectomy), the biopsies, cytologies, and cell
      blocks were concordant in 15 cases (28%). Biopsy results were found to agree more
      closely with the cell block preparation than the ThinPrep slide in eight cases,
      and were found to identify more closely with the ThinPrep slide in four cases.
      Biopsy showed changes that were less severe than those found on either cytology
      or cell block in 23 cases (43%). Biopsy demonstrated changes that were more
      severe than those observed on either cytology or cell block in 4 cases (7%).
      CONCLUSIONS: The results of the current study demonstrate that this technique is
      feasible and useful as a complement to routine gynecologic cytology slide
      preparation and examination.

PMID- 12209662
TI  - Measuring sensitivity in gynecologic cytology: a review.
AB  - BACKGROUND: The sensitivity of gynecologic cytology has been measured in several
      different ways. The current review summarizes the major sources of bias and the
      results of these efforts. METHODS: In the current study, a review of the
      literature was conducted. RESULTS: The major sources of bias in measuring the
      sensitivity of gynecologic cytology are a lack of reproducibility, bias in the
      review process, bias in case selection, selection and correction of the gold
      standard, and the value of surrogate markers. Despite these sources of variation,
      the sensitivity of the Papanicolaou (Pap) smear is relatively stable, ranging
      from 50-75% if a single consistent threshold is used, to up to 94% if either
      Autopap-directed rescreening or thin-layer methods are used to diagnose high
      grade squamous intraepithelial lesions using a threshold of atypical squamous
      cells of undetermined significance. Methods for the routine evaluation of
      sensitivity currently are not available and may be difficult to devise.
      CONCLUSIONS: The sensitivity of the Pap smear in study situations is well known.
      Whether these reflect performance in real life is not known, and methods to
      compare performance in real life are not available.

PMID- 12209663
TI  - Cervical smear interpretations in women with a histologic diagnosis of severe
      dysplasia: factors associated with discrepant interpretations.
AB  - BACKGROUND: Because most low-grade squamous intraepithelial lesions (LSIL)
      regress spontaneously, the appropriate follow-up of women with a cytologic
      diagnosis of LSIL has engendered discussion. This retrospective study was
      undertaken to assess the feasibility of limiting colposcopy to women with
      cytologic interpretations of high-grade squamous intraepithelial lesions (HSIL)
      in a high-risk population. METHODS: The pathology computer files (including files
      from January to December 1997) of The University Hospital, University of Oklahoma
      Health Sciences Center, revealed 197 women whose histologic samples were coded as
      severe dysplasia. Of these, 138 had a cervical smear interpreted in our
      laboratory before the colposcopic visit. On review, the tissue samples of 119
      women met consensus criteria for severe dysplasia. RESULTS: Original cytologic
      diagnoses for 119 cytologic smears included 80 (62.7%) that were interpreted as
      HSIL. After retrospective review, 28 cases with LSIL or less were reclassified as
      HSIL and were considered to be discrepant for the purpose of this study. Major
      confounding factors in the original categorization include lack of consistency
      among the pathologists for the interpretation of metaplastic patterns and
      specimen adequacy, particularly air-drying artifact. Eleven cases (10.2%) did not
      have cells identifiable as HSIL because of sampling error and/or severe air
      drying artifact. CONCLUSIONS: These results indicate that a substantial number of
      histologically verified cases of severe dysplasia can have a smear interpretation
      of LSIL or less. The factors that hampered recognition of the true severity of
      the lesion in this series were identified and tabulated.

PMID- 12209664
TI  - Intraoperative touch imprint of sentinel lymph nodes in breast carcinoma
      patients.
AB  - BACKGROUND: Sentinel lymph node examination in patients with breast carcinoma has
      been gaining in popularity. Currently, there is no standard intraoperative
      assessment of sentinel lymph nodes. To assess the utility of an intraoperative
      touch imprint (TI) evaluation, the authors compared TI cytology with surface
      hematoxylin and eosin (H&E) histology in sentinel lymph nodes from patients with
      breast carcinoma. METHODS: Sixty five sentinel lymph node biopsy cases were
      identified. Diagnoses from TI and surface H&E histologic sections were compared.
      RESULTS: Touch imprint had a specificity of 100%, a negative predictive value of
      88%, a sensitivity of 65%, and a false negative rate of 9% per sentinel lymph
      node biopsy case. Eighty three percent of the false negative TI cases were due to
      micrometastasis. Preoperative chemotherapy, primary tumor type, and primary tumor
      size did not significantly contribute to false negative events. Touch imprint
      identified 67% of the cases that required completion axillary dissection.
      CONCLUSIONS: Touch imprint is a reliable and accurate intraoperative technique,
      with the potential to save a significant number of patients morbidity and the
      cost of a second surgical procedure to remove axillary lymph nodes. The
      difficulty of identifying micrometastases appeared to be the major source of
      false negative events, a problem that is not unique to TI cytology.

PMID- 12209666
TI  - "Histiocytoid" cells in fine-needle aspirations of papillary carcinoma of the
      thyroid: frequency and significance of an under-recognized cytologic pattern.
AB  - BACKGROUND: Although the classic cytologic features of papillary carcinoma of the
      thyroid in fine-needle aspirates have been well described, one uncommon feature,
      a vacuolated, histocyte-like cell without classic nuclear changes of papillary
      carcinoma, has been less well characterized. METHODS: The author reviewed a large
      series of thyroid aspirates for specimens with these cytologic features. RESULTS:
      Seven specimens were identified, representing approximately 6% of all aspirates
      with the features of papillary carcinoma and less than 0.5% of all aspirates. The
      cells resembled histiocytes but were larger, more atypical, and keratin positive
      in the one specimen that was tested. The cells had enlarged nuclei with abundant
      cytoplasm that often was vacuolated. The nuclei had grainy chromatin, occasional
      nucleoli, and lacked grooves and prominent pseudoinclusions. The background
      showed numerous, hemosiderin-laden macrophages typical of cyst contents in only
      three specimens. Calcifications were present in six specimens and resembled
      psammoma bodies in two specimens. Three specimens showed papillary carcinoma at
      resection, two specimens had other passes from the same nodule that were
      diagnostic of papillary carcinoma, and two specimens were from recent patients
      without follow-up. Only one of the three resected tumors showed prominent cystic
      change. None of 50 aspirates that were diagnosed as benign cyst contents had
      similar atypical cells, nor did resections of six predominantly cystic, benign
      lesions. CONCLUSIONS: Histiocytoid cells are present in as many as 6% of all
      aspirates in which some features of papillary carcinoma are present. Increased
      awareness of these cells may help improve the sensitivity of fine-needle
      aspiration for the diagnosis of papillary carcinoma of the thyroid.

PMID- 12209665
TI  - Endoscopic ultrasound-guided fine-needle aspiration biopsy: a study of 103 cases.
AB  - BACKGROUND: Endoscopic ultrasound (EUS) provides detailed imaging of both
      intramural and extramural structures within the abdomen and mediastinum. However,
      EUS is limited in its ability to differentiate an inflammatory/reactive process
      from a malignancy. Fine-needle aspiration biopsy (FNAB), coupled with EUS, allows
      for the sampling of the target lesion under ultrasound guidance in real time. To
      better evaluate the clinical utility and efficiency of EUS-FNAB, a retrospective
      analysis of the first 103 EUS-FNABs performed at our institute was undertaken.
      METHODS: EUS-FNABs was performed in 80 patients with 103 lesions. Both air-dried
      and alcohol-fixed smears were prepared and stained with Diff-Quik (American
      Scientific Products, McGraw Park, IL) and Papanicolaou stains, respectively. In
      addition, ThinPrep slides (Cytyc, Boxborough, MA) and cell blocks, when
      additional material was available, were also prepared. Immunohistochemical stains
      were performed on cell blocks wherever required. Cytologic diagnoses were then
      correlated with the final diagnoses. The latter was based on histologic
      examination of biopsies/resected pathology materials (n = 54) and clinical follow
      up (n = 48). Follow-up information was not available for one lesion. RESULTS: Of
      103 EUS-FNABs, 42 FNABs were from the pancreas, 38 from the lymph nodes (10
      mediastinal and 28 intraabdominal), 10 from the gastrointestinal tract, 7 from
      the liver, 4 from the adrenal gland, 1 from the biliary tract, and 1 from a
      retroperitoneal mass. The mean number of passes to obtain diagnostic materials
      was 3.3. Of 103 EUS-FNABs, 45, 9, 6, and 37 were reported as malignant,
      suspicious, atypical, and benign, respectively. Six FNABs were nondiagnostic. The
      authors did not encounter any false-positive cases. There were three false
      negative cases (two pancreatic carcinomas and one gastrointestinal stromal tumor
      of the stomach). No complications were encountered. The sensitivity, specificity,
      and accuracy were 71%, 100%, and 81%, respectively. If the FNABs that were
      classified as suspicious were considered as malignant, the sensitivity,
      specificity, and accuracy were 86%, 100%, and 91%, respectively. CONCLUSIONS: EUS
      FNAB is a safe and accurate diagnostic procedure for the evaluation of intramural
      and extramural lesions of the gastrointestinal tract. In the majority of cases,
      it obviates the need for more invasive diagnostic procedures to obtain a tissue
      diagnosis.

PMID- 12209667
TI  - Immunocytochemical analysis of breast cells obtained by ductal lavage.
AB  - BACKGROUND: Intraductal breast fluids containing exfoliated mammary epithelial
      cells can be harvested from the breast by ductal lavage to screen for disease
      associated cytologic abnormalities. In addition to epithelial cells, breast
      fluids contain large numbers of mammary foam cells, and the tissue of origin of
      these foam cells has been the subject of controversy for many years.
      Immunocytochemical, morphologic, and molecular studies variously have supported a
      mammary epithelial origin versus a histiocytic origin for this cell type. In the
      current study, the authors performed immunocytochemical analysis with epithelial
      specific and macrophage specific antibodies to characterize and quantify breast
      cells obtained by ductal lavage. METHODS: Breast fluids were harvested from 19
      individual breast ducts in 15 female patients by ductal lavage. Cells from each
      specimen were processed for immunocytochemical staining using the AE1/AE3
      multicytokeratin and CD68 (clone KP1) monoclonal antibodies. Cells were
      classified as mammary epithelial cells or mammary foam cells on the basis of
      morphologic criteria, and the cells were counted and evaluated for
      immunoreactivity with epithelial specific and macrophage specific antibodies.
      RESULTS: The CD68 macrophage specific antibody stained all ductal lavage cells
      that exhibited foam cell morphology. The AE1/AE3 multicytokeratin antibody
      demonstrated strong, positive staining of cells that exhibited epithelial
      morphology but failed to demonstrate significant staining of mammary foam cells.
      The lavage specimens contained a range of 3040-278,850 epithelial cells and 2230
      90,480 foam cells. The median numbers of epithelial cells and foam cells per
      lavage sample were 15,680 and 29,200, respectively. The ratio of epithelial cells
      to foam cells varied among specimens ranging from 3.4 to 0.09 (median, 0.8).
      Seven of 19 lavage specimens contained more epithelial cells than foam cells,
      whereas 12 samples contained a greater proportion of foam cells. CONCLUSIONS:
      Immunocytochemical analysis using the AE1/AE3 multicytokeratin and CD68
      antibodies supports a histiocytic origin for the majority of mammary foam cells
      harvested from the ductal system of the human breast by ductal lavage. Although
      mammary foam cells constitute a significant proportion of the cellular population
      obtained by ductal lavage, thousands of epithelial cells also are harvested.

PMID- 12209668
TI  - Transitional cell metaplasia of the uterine cervix is related to human
      papillomavirus: molecular analysis in seven patients with cytohistologic
      correlation.
AB  - BACKGROUND: Transitional cell metaplasia of the uterine cervix is an under
      recognized entity in cervical pathology. The underlying etiology and biologic
      significance remains uncertain. The thin-layer cytology findings and association
      with human papillomavirus (HPV) have not been studied thoroughly. METHODS: The
      authors retrospectively reviewed the clinical findings, thin-layer cytology and
      histologic features of pure transitional cell metaplasia of the uterine cervix
      occurring in seven perimenopausal or postmenopausal Chinese women at Pamela Youde
      Nethersole Eastern Hospital, Hong Kong, during the period from January, 1998 to
      April, 2001. Molecular techniques for HPV screening and genotyping using
      polymerase chain reaction and restriction fragment length polymorphism analysis
      were employed in the thin-layer cytology specimens and paraffin block material.
      RESULTS: In all seven patients, transitional cell metaplasia represented an
      incidental histologic finding. It occurred in the ectocervix, transformation
      zone, endocervix, or vagina. Histologically, it resembled urothelium of the
      urinary bladder and was comprised of multilayers of mitotically inactive,
      immature epithelial cells with vertically aligned oval nuclei, fine chromatin,
      indistinct nucleoli, and conspicuous longitudinal nuclear grooves. The
      superficial cells were oriented more horizontally and contained pale-staining
      cytoplasm similar to umbrella cells. Features consistent with transitional cell
      metaplasia were identified in two of seven preoperative thin-layer preparations.
      Cytologically, the affected parabasal cells recapitulated the features that were
      seen in histologic sections. In addition to the bland nuclear morphology and
      longitudinal nuclear grooves, the cell borders appeared distinct, and the
      appearance of a perinuclear cytoplasmic halo was common. Sometimes, the
      metaplastic cells assumed a spindle shape and appeared as cohesive, streaming
      cell clusters. Molecular study successfully demonstrated the presence of HPV in
      all seven patients, mostly in the liquid-based cytology samples. In general, the
      viral DNA load was relatively low; and, for samples in which HPV genotyping was
      feasible, HPV type 58 was the prevalent genotype. CONCLUSIONS: The current study
      demonstrates that transitional cell metaplasia of the uterine cervix is related
      to HPV. It also carries a distinctive cytologic appearance in thin-layer
      preparations. Based on the limited follow-up data from a small number of reported
      patients, transitional cell metaplasia seems to run an indolent clinical course.
      However, its peculiar association with HPV and its possible correlation, both
      morphologic and histogenetic, with cervical intraepithelial neoplasia need
      further investigation.

PMID- 12209670
TI  - Gemcitabine and platinum combinations in pancreatic cancer.
AB  - Progress in the treatment of pancreatic cancer in the past several decades has
      been very modest. Several new agents with activity against this disease have been
      identified. Of these, gemcitabine appears to be the most promising when used in
      combination with other drugs. Gemcitabine and cisplatin combinations have been
      tested in several studies. The major toxicity reported to occur with the
      gemcitabine-cisplatin combination is myelosuppression, which is greater than that
      encountered with single-agent gemcitabine. However, episodes of neutropenic fever
      or spontaneous bleeding are reported to be very infrequent. Pilot Phase II
      studies combining gemcitabine with cisplatin have shown improved outcomes in
      objective response rates and survival; however, these findings must be confirmed
      in larger randomized studies.

PMID- 12209671
TI  - Gemcitabine in combination with 5-fluorouracil with or without folinic acid in
      the treatment of pancreatic cancer.
AB  - Pancreatic cancer is one of the most frequently reported gastrointestinal tumors
      and has been reported to have a 5-year survival rate of < 5%. It is most commonly
      diagnosed at an advanced stage and until recently, the most frequently
      administered treatment for patients with advanced disease has been palliative 5
      fluorouracil (5-FU)-based chemotherapy. However, in clinical trials, the novel
      antinucleoside gemcitabine is currently considered the standard of care and has
      demonstrated both a survival benefit over 5-FU and an improvement in disease
      related symptoms in those patients with advanced disease. The current review
      presents an overview of recently completed and ongoing clinical trials of
      gemcitabine/5-FU combination therapy for pancreatic cancer. In these trials, the
      administration of 5-FU varied widely from bolus injection to 24-hour infusion to
      protracted infusion over several weeks. These variations make a definitive
      judgment of this combination difficult, especially because the majority of the
      data represent only Phase I and Phase II study results. Although a recently
      completed randomized Phase III trial of gemcitabine plus bolus 5-FU versus
      gemcitabine failed to show a clinically meaningful survival benefit for the
      combination arm, current data indicate that other gemcitabine/5-FU combinations
      might provide a therapeutic advantage over gemcitabine alone. However, the
      results of ongoing Phase III studies must be reviewed before a definitive
      statement can be made regarding the value of this combination in the treatment of
      pancreatic cancer.

PMID- 12209672
TI  - Gemcitabine-based therapy in pancreas cancer: gemcitabine-docetaxel and other
      novel combinations.
AB  - Since its approval in 1998 by the Food and Drug Administration, gemcitabine has
      rapidly become accepted as a standard part of palliative therapy for patients
      with advanced pancreatic cancer. It has modest activity when used as a single
      agent, and this has led to numerous studies combining it with other active
      agents, including cytotoxic as well as biologic and targeted therapies. Numerous
      Phase II studies suggest that the combinations may have greater activity than
      single agent therapy. However, randomized trials concerning this are still in
      progress. In the current article, a variety of gemcitabine-based novel
      combinations showing promising activity are reviewed.

PMID- 12209673
TI  - The pemetrexed/gemcitabine combination in pancreatic cancer.
AB  - Gemcitabine has modest antitumor activity in advanced pancreatic cancer. New
      agents are clearly needed. Pemetrexed (ALIMTA) is a novel antifolate that
      inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide
      ribonucleotide formyltransferase. Pemetrexed has shown in vitro activity against
      pancreatic cancer cell lines. In a Phase I trial of pemetrexed, two patients with
      pancreatic cancer achieved partial responses on the once every 21 days schedule.
      A Phase II trial of pemetrexed in patients with advanced pancreatic cancer showed
      an objective response rate of 6%, a one year survival of 28%, and a mild toxicity
      profile. The combination of pemetrexed and gemcitabine is synergistic in vitro
      and was broadly active in a Phase I trial. The pemetrexed/gemcitabine combination
      was evaluated in a Phase II trial in 42 patients with advanced pancreatic cancer.
      The promising activity observed in this study has led to an ongoing
      international, randomized, Phase III trial in 520 patients comparing the
      pemetrexed/gemcitabine combination with gemcitabine alone.

PMID- 12209674
TI  - On the development of gemcitabine-based chemoradiotherapy regimens in pancreatic
      cancer.
AB  - The use of chemotherapy with concurrent radiation therapy remains a standard
      treatment option for patients with unresectable or resected adenocarcinoma of the
      pancreas. This treatment strategy is based in large part on data from serial
      Gastrointestinal Tumor Study Group trials that have included 5-fluorouracil.
      Unfortunately, the majority of patients continue to succumb to the disease
      process. Recently, there has been a resurgence in clinical trials utilizing
      gemcitabine as a single agent, in combination chemotherapy regimens, and with
      concurrent radiation therapy. Use with concurrent radiation therapy is based in
      part on laboratory studies investigating mechanisms of radiosensitization and
      strategies that might increase the therapeutic index. In the current review, the
      authors summarize the preclinical data that support the use of gemcitabine as a
      radiosensitizing agent and the clinical trials that have been conducted to date.
      Issues regarding the use of gemcitabine in concurrent radiotherapy regimens need
      to be viewed in the context of both local and distant disease control, given the
      radiosensitizing and systemic activity of this agent.

PMID- 12209675
TI  - New applications of gemcitabine and future directions in the management of
      pancreatic cancer.
AB  - Gemcitabine has been reported to be an active agent in pancreatic cancer. Recent
      applications have included the use of a fixed-dose rate regimen in patients with
      advanced pancreatic cancer based on the observation that deoxycytidine kinase is
      saturated at the plasma gemcitabine concentrations achieved with standard
      infusion, thereby limiting the accumulation of intracellular gemcitabine
      triphosphate. In a Phase II study, this regimen was associated with survival
      rates better than those typically observed in patients with advanced disease.
      Gemcitabine also has been assessed as a radiosensitizer in locally advanced
      cancer and although toxicity was significant, objective responses were observed
      and included tumor response, which permitted curative resection. Future
      directions in therapy for pancreatic cancer include the development of agents
      targeting signal transduction pathways and nuclear transcription factors based on
      the continually improving understanding of the role of molecular events in
      carcinogenesis.

PMID- 12209676
TI  - How does interferon work? Does it even matter?

PMID- 12209677
TI  - Selection and description of cancer clinical trials participants--science or
      happenstance?
AB  - BACKGROUND: The selection of clinical trials participants is a critical step in
      study design, because it affects the generalizability of recommendations made on
      the basis of trial results and public acceptance of medical research. The authors
      assessed the heterogeneity of subgroups in cancer treatment and prevention trials
      and the analysis of subgroups in the evaluation of trial outcomes. METHODS: The
      authors reviewed published reports (1990-2000) of cancer prevention and treatment
      trials from 11 journals. They report here on all Phase III cancer treatment and
      prevention trials that had at least 100 participants and were conducted among
      adults in the United States. A structured abstract was developed and used to
      extract data from the 261 published reports. Descriptive summaries of the
      abstracted data provided the information included in this systematic review.
      RESULTS: Age and gender of study participants were reported in more than 90% of
      these trials, whereas fewer than 30% of the trials reported race or ethnicity.
      Gender was reported as an explicit criterion for participant selection primarily
      in studies of gender specific malignancies. Race and ethnicity were reported as
      explicit selection criteria for participant selection for five of the prevention
      trials and for none of the cancer treatment trials. The 105 treatment trials that
      reported including both men and women had 42,355 participants, and 38.6% of those
      participants were women. The 26 prevention trials that reported including both
      men and women had 73,995 participants, and 34.7% of those participants were
      women. Fifty-seven treatment trials reported participant ethnic diversity: There
      were 45,815 participants, with 10.5% African-American participants and with less
      than 1% Hispanic, Asian, or Native American participants. Seventeen prevention
      trials reported participant ethnic diversity: There were 91,741 participants,
      with 5.5% African-American participants, 1.7% Hispanic participants, and less
      than 1% Asian or Native American participants. CONCLUSIONS: Cancer treatment and
      prevention trial reports provide scant information about participant race and
      ethnicity. Such studies use participant selection criteria that do not define
      diverse subgroups, and few subgroup analyses are conducted. Improvements in the
      selection, reporting, and analysis of clinical trials participants are needed.

PMID- 12209678
TI  - Hormone replacement therapy and breast carcinoma risk in Hispanic and non
      Hispanic women.
AB  - BACKGROUND: Hormone replacement therapy (HRT) alleviates menopausal symptoms and
      prevents osteoporosis, but there is concern that long-term use may have an
      adverse impact on breast carcinoma risk. Epidemiologic studies report
      inconsistent findings regarding the relationship between HRT and postmenopausal
      breast carcinoma risk and there is little information on the HRT-associated risk
      among minority women. METHODS: To investigate the effects of HRT on breast
      carcinoma risk among Hispanic women, we examined data from the New Mexico Women's
      Health Study (NMWHS), a statewide case-control study comprising 366
      postmenopausal women with breast carcinoma and 403 controls. Conditional logistic
      regression was used to estimate the odds ratios (OR) and 95% confidence intervals
      (95% CI). RESULTS: After adjustment for sociodemographic, medical, and
      reproductive factors, we found an increased risk associated with long-term users
      of estrogen replacement therapy (ERT; OR for ERT use longer than 140 months was
      2.57, 95%CI, 1.25-5.28, compared with ERT use shorter than 17 months). In
      addition, there was a positive trend with the duration of ERT use (P < 0.01).
      Hispanic postmenopausal women appeared to be at a significantly greater risk than
      non-Hispanic white women (OR for ERT use longer than 140 months in Hispanics was
      5.53, 95%CI, 1.47-20.87; OR in non-Hispanics was 2.65, 95%CI, 0.95-7.34, compared
      with ERT use shorter than 17 months). In contrast, no significant association was
      observed for combined estrogen-progesterone use in either Hispanic or non
      Hispanic women. CONCLUSIONS: The results of this study indicated that
      postmenopausal women had significantly increased breast carcinoma risk for long
      term ERT use. The risks among Hispanic women were substantially higher than among
      non-Hispanic white women although they were not statistically significant.

PMID- 12209679
TI  - Immunohistochemical expression of erythropoietin and erythropoietin receptor in
      breast carcinoma.
AB  - BACKGROUND: Erythropoietin (Epo), induced by hypoxia, controls the survival,
      proliferation, and differentiation of Epo receptor (EpoR)-bearing erythroid
      progenitors and plays a role in the protection of neurons from hypoxic damage.
      Hypoxia in malignant disease is associated with invasion, metastasis, resistance
      to therapy, and selection for cells with diminished apoptotic potential. The
      authors recently demonstrated the basal and hypoxia-stimulated expression of Epo
      and EpoR in human breast carcinoma cell lines and in breast carcinomas,
      suggesting a role for autocrine Epo signaling in the hypoxic adaptations of
      mammary neoplasms. METHODS: The authors characterized the expression of Epo and
      EpoR by immunohistochemistry in 184 invasive mammary carcinomas and 158 in situ
      mammary carcinomas and benign mammary epithelium. They analyzed the correlation
      of Epo and EpoR immunostaining with clinicopathologic tumor features and the
      patients' smoking history. RESULTS: Benign mammary epithelial cells showed weak
      to-moderate expression of Epo and EpoR. EpoR immunostaining was increased in
      carcinomas compared with benign epithelium both in nonsmokers and smokers, and
      Epo immunostaining was increased in carcinomas compared with benign epithelium in
      nonsmokers but not in smokers. Prominent Epo staining was seen in tumor cells
      adjacent to necrotic areas and at the infiltrating edge of tumors. EpoR staining,
      but not Epo staining, was significantly greater in tumors that showed high
      histologic grade, tumor necrosis, lymphovascular invasion, lymph node metastases,
      and loss of hormone receptor expression. CONCLUSIONS: The current findings
      suggest that increased EpoR expression may play an important role in breast
      carcinogenesis. The induction of autocrine or paracrine Epo signaling may
      represent a novel mechanism by which hypoxia can promote breast carcinoma.

PMID- 12209680
TI  - Role of ultrasound-guided fine-needle aspiration of indeterminate and suspicious
      axillary lymph nodes in the initial staging of breast carcinoma.
AB  - BACKGROUND: Ultrasound (US) is more sensitive than physical examination alone in
      determining axillary lymph node involvement during preliminary staging of breast
      carcinoma. Due to occasional overlap of sonographic features of benign and
      indeterminate lymph nodes, fine-needle aspiration (FNA) of sonographically
      indeterminate/suspicious lymph nodes can provide a more definitive diagnosis than
      US alone. This study was undertaken to determine the diagnostic accuracy of US
      guided FNA of indeterminate/suspicious/metastatic-appearing axillary lymph nodes
      during the initial staging of breast carcinoma. METHODS: The cytology of 103
      cases of US-guided FNA of nonpalpable indeterminate/suspicious/metastatic
      appearing lymph nodes was compared with the final histopathologic status of the
      entire axilla after axillary dissection. The final axillary lymph node status was
      categorized as either negative when all lymph nodes were negative for metastasis
      or positive when there was evidence of metastasis in one or more lymph nodes. The
      sensitivity, specificity, diagnostic accuracy, and false-negative rate of US
      guided FNA of nonpalpable axillary lymph nodes in the preliminary staging process
      were calculated. RESULTS: In 51 of 103 cases (49.5%), the US-guided FNA and
      histopathology were both positive for metastasis. In 24 of 103 cases (23.3%),
      both were negative. The apparent false-positive FNA in 16 (15.5%) cases was
      explained by the complete response of the metastatic lymph nodes to neoadjuvant
      chemotherapy in the interval between FNA and axillary dissection. In 12 cases
      (11.6%), US-guided FNA was negative, but metastasis was seen in histologic
      sections. All cases with three or more lymph nodes with metastatic disease and
      93% of those with metastatic deposit measuring more than 0.5 mm were detected by
      US-guided FNA. The probability of detecting lymph nodes with smaller metastatic
      deposit measuring less than 0.5 cm was 44%. The overall sensitivity of US-guided
      FNA was 86.4%, the specificity was 100%, the diagnostic accuracy was 79.0%, the
      positive predictive value was 100%, and the negative predictive value was 67%.
      CONCLUSIONS: US-guided FNA of nonpalpable indeterminate and suspicious axillary
      lymph nodes is a simple, minimally invasive, and reliable technique for the
      initial determination of axillary lymph node status in breast carcinoma. The
      common causes of discrepancy between the initial and final axillary lymph node
      status include failure to visualize all lymph nodes during US examination, small
      sized metastases, and preoperative neoadjuvant chemotherapy.

PMID- 12209681
TI  - Survey of oncologists' perceptions of barriers to accrual of older patients with
      breast carcinoma to clinical trials.
AB  - BACKGROUND: Prior research has documented the under-representation in clinical
      trials of older patients with cancer. In part of a larger study to test the
      magnitude of these barriers to entering eligible older patients with carcinoma of
      the breast into clinical trials (Cancer and Leukemia Group B [CALGB] trial 9670),
      barriers to accruing eligible older patients to clinical trials were obtained
      from the physician's perspective. METHODS: One hundred fifty-six physicians (85%
      oncologists) who treated patients with breast carcinoma at 10 CALGB institutions
      completed a questionnaire concerning what they perceived as barriers to enrolling
      older patients with breast carcinoma on clinical trials and possible
      interventions that may improve accrual. RESULTS: Physicians' perceptions of the
      most important barriers to accrual of older patients were: 1) elderly patients
      have significant comorbid conditions that are not excluded by the protocol but
      that may affect how they would respond to treatment (16%); elderly patients have
      difficulty understanding what is required in a complicated treatment trial,
      resulting in poor compliance (16%); treatment toxicity (14%); and elderly
      patients often do not meet the eligibility criteria (15%). Oncologists most
      frequently suggested that the most effective interventions for improving the
      accrual of elderly patients to trials included making personnel available in the
      clinic to explain clinical trials to older patients and their families (25%) and
      providing physicians with educational materials concerning treatment toxicity in
      the elderly (18%). CONCLUSIONS: Physicians viewed barriers to accruing older
      patients with breast carcinoma to clinical trials as multidimensional, with the
      most important involving protocol requirements, treatment specific issues, and
      older patients' medical and cognitive characteristics. Thus, a variety of
      interventions would be needed to improve accrual of older patients to clinical
      trials, including increasing physicians' knowledge concerning treatment toxicity
      in the elderly, simplifying protocol requirements, and reducing treatment
      toxicity.

PMID- 12209683
TI  - Role of metallothioneins in irradiated human rectal carcinoma.
AB  - BACKGROUND: Metallothioneins (MT) are low-molecular weight, metal-binding
      proteins that play a role in cellular proliferation and differentiation, as well
      as in cellular defense mechanisms. They act as scavengers of free radicals
      produced by irradiation. A number of in vitro and in vivo studies have linked
      overexpression of cellular MT with tumor cell resistance to radiation. This is
      the first study that investigates whether MT expression is involved in the
      radioresistance of rectal carcinoma. METHODS: Using a mouse monoclonal antibody,
      MT expression was analyzed by immunohistochemistry on surgical samples (n = 85)
      from 85 patients with locally advanced rectal carcinoma who were treated
      preoperatively with a hyperfractionated and accelerated radiotherapy schedule and
      on tumor biopsies (n = 13) obtained before treatment. The potential correlations
      between MT expression and pathologic variables and survival were examined.
      RESULTS: MT were expressed strongly in both the cytoplasm and nucleus of tumor
      cells in 7 biopsy and 42 surgical samples. A comparison of MT expression in
      biopsy and surgical specimens showed that MT expression did not change after
      irradiation in most cases. Against all expectations, MT were expressed more
      frequently in tumors from responders than in those from the nonresponders (P =
      0.02). There was no correlation between MT expression and tumor stage, histology
      after radiotherapy, or survival. CONCLUSION: These findings do not Cansupport the
      hypothesis that MT overexpression at the end of radiotherapy is a marker for
      radiation resistance.

PMID- 12209682
TI  - Salvage chemotherapy for recurrent spinal cord ependymona.
AB  - BACKGROUND: Ependymomas are reported to constitute 4% of all primary central
      nervous system (CNS) malignancies in adults, 30% of which occur in the spinal
      cord. A prospective Phase II study to determine toxicity and response to chronic
      oral etoposide in patients with recurrent low-grade intramedullary spinal cord
      ependymoma (SCE) was conducted. METHODS: Ten patients (6 males and 4 females with
      a median age of 30 years) with recurrent SCE were treated with oral etoposide
      (50mg/m(2)/day given daily for 21 days followed by a 14-day break and then
      repeated constituted a cycle of therapy). All patients had failed surgery and
      radiotherapy and four patients had failed one prior chemotherapy. Blood counts
      were obtained weekly, and neurologic examination and a chemistry panel were
      performed monthly. Contrast-enhanced magnetic resonance imaging of the spine was
      performed every 8 weeks after a cycle of etoposide and before the next cycle of
      chemotherapy was initiated. RESULTS: Treatment-related complications included
      alopecia in 9 patients, nonbloody diarrhea in 6 patients, a baseline weight loss
      of > 10% in 5 patients, Grade (according to the National Cancer Institute Common
      Toxicity Scale) 3-4 neutropenia in 3 patients, Grade 3-4 thrombocytopenia in 3
      patients, and Grade 3-4 anemia in 2 patients. There were no treatment-related
      deaths reported. After 1 cycle of etoposide, 3 patients (30%) demonstrated
      progressive disease, 2 patients (20%) achieved a partial response, and 5 patients
      (50%) maintained stable disease. The overall median response or stable disease
      duration (disease-free progression) was 15 months (range, 2.5-45+ months). The
      overall median survival was 17.5 months (range, 3-45+ months). CONCLUSIONS:
      Chronic oral etoposide appears to be well tolerated, has modest toxicity, and had
      apparent activity in the small cohort of adults in the current study with
      surgically and medically refractory, recurrent, intradural intramedullary SCE.

PMID- 12209684
TI  - Does HER2/neu expression provide prognostic information in patients with advanced
      urothelial carcinoma?
AB  - BACKGROUND: Muscle-invasive urothelial carcinoma of the bladder is a highly
      lethal malignancy, particularly in the setting of locally advanced or metastatic
      disease. Prior reports of HER2/neu (c-erbB-2 or HER2) expression in bladder
      carcinoma have been mixed; therefore, its value in predicting metastasis or
      response to therapy has not been established in this tumor type. Thus, the
      authors evaluated a possible correlation between HER2 expression in patients with
      high-grade, muscle-invasive urothelial carcinoma of the bladder and outcome in
      patients who received paclitaxel-based chemotherapy. METHODS: Archival tumor
      tissues from patients with advanced urothelial carcinoma who were enrolled on two
      clinical trials of paclitaxel-based chemotherapy regimens were analyzed for
      HER2/neu expression by immunohistochemistry (IHC). The authors correlated HER2
      expression by IHC with clinical outcomes, such as response rate, progression free
      survival, and overall survival, using univariate analysis. RESULTS: Thirty-nine
      tumor specimens were assessed for HER2 expression, most of which (70%) were
      collected from patients with metastatic disease. All were high-grade urothelial
      carcinomas (transitional cell carcinomas, Grade 3). Strong HER2 expression
      (2+/3+) was seen in 28 patients (71%). Patients with responding disease had an
      HER2 expression rate of 78%, similar to the rate seen in patients with stable
      disease (75%). In contrast, patients with progressive disease had an HER2
      expression rate of 50%, although this difference did not reach statistical
      significance. However, univariate analysis showed that increased HER2 expression
      predicted an improvement in progression free and overall survival. When HER2
      status was used as a dichotomous variable, tumors with positive HER2 expression
      did not have any association with response or with progression free survival;
      however, positive HER2 status was associated significantly with a decreased risk
      of death (P = 0.03). CONCLUSIONS: This study of HER2 expression in bladder
      carcinoma focused on patients who were treated prospectively in a standardized
      fashion, unlike prior studies that have evaluated banked, archival specimens. The
      authors confirmed the findings of others that high-grade, muscle-invasive
      urothelial carcinoma of the bladder has a significant rate of HER2 expression
      (71%). However, contrary to other reports, the current study found that HER2
      expression in the context of paclitaxel-based chemotherapy decreased the risk of
      death significantly. Further research is warranted on the possible association of
      HER2 expression with chemosensitivitiy in urothelial carcinoma as well as the
      efficacy of HER2-targeted therapies (such as trastuzumab) for patients with high
      grade, muscle-invasive urothelial carcinoma of the bladder.

PMID- 12209685
TI  - Validation of a biopsy-based pathologic algorithm for predicting lymph node
      metastases in patients with clinically localized prostate carcinoma.
AB  - BACKGROUND: The authors validated an algorithm for the preoperative prediction of
      lymph node (LN) metastases in patients with clinically localized prostate
      carcinoma. The algorithm was applied to sextant biopsy material and radical
      retropubic prostatectomy (RRP) stage obtained from a cohort of men who were
      treated at the authors' institution. METHODS: Four hundred forty-three patients
      underwent systematic sextant biopsy and RRP with staging lymphadenectomy. The
      original algorithm was based on systematic sextant biopsy data and classified
      patients into three risk groups for LN metastases based on the biopsy result. If
      > or = 4 of 6 biopsies contained any Gleason Pattern 4 disease, then the patient
      was at high risk for LN metastases (45%). Patients with > or = 1 of 6 biopsies
      with dominant Gleason Pattern 4 disease (excluding high-risk patients) had an
      intermediate predicted risk (19%) of LN metastases. All other patients had a low
      predicted risk of LN metastases (2.2%). The authors assed the percentage of
      patients who were positive and negative for LN metastases and calculated the
      specificity and negative predictive value in the series when patients were
      classified according to the original algorithm. RESULTS: Twenty of 443 patients
      had intraoperative LN metastases. When applied to the current data, the Hamburg
      algorithm classified 404 patients in the low-risk group, 30 patients in the
      intermediate-risk group, and 9 patients in the high risk group. The incidence of
      LN metastases was 2.47% in the low-risk group, 20% in the intermediate-risk
      group, and 44.4% in the high-risk group. The negative predictive value for the
      low-risk group was 97.52%, and the specificity was 94.14%. CONCLUSIONS: The
      Hamburg algorithm proved a valid tool for the prediction of lymphatic spread in
      this validation study on data from the authors' institution. The algorithm may
      serve as a tool to select patients who do not need to undergo pelvic
      lymphadenectomy at the time they undergo RRP, hence reducing morbidity and
      expense. More importantly, with the increasing numbers of men undergoing
      treatment options in whom LN dissection is not performed, this validated
      algorithm provides an important selection basis regarding the appropriateness of
      a therapy that does not routinely include LN staging.

PMID- 12209686
TI  - Phase II study of paclitaxel plus carboplatin in patients with advanced carcinoma
      of the urothelium and renal dysfunction (E2896): a trial of the Eastern
      Cooperative Oncology Group.
AB  - BACKGROUND: Chemotherapy options for the patients with advanced urothelial
      carcinoma and renal dysfunction are limited. The authors performed a Phase II
      trial of paclitaxel plus carboplatin in patients with advanced carcinoma of the
      urothelium and renal dysfunction. METHODS: Forty-two patients were accrued; 37
      eligible patients were treated. Patients received paclitaxel 225 mg/m(2) over
      three hours followed by carboplatin targeted area under the concentration-time
      curve = 6 mg/mL. minute every three weeks for up to six cycles. RESULTS: The
      median number of cycles received was four (range, one to six). The objective
      response rate was 24.3% (95% confidence interval, 11.9-41.7%). The median
      progression free survival was 3 months and the median overall survival was 7.1
      months. The number of poor prognostic risk factors (Eastern Cooperative Oncology
      Group performance status > 1 or lung, liver, or bone metastases) significantly
      predicted for survival. The most common > or = 1 Grade 3 toxicities included
      granulocytopenia (60%) and neurotoxicity (35%). CONCLUSIONS:
      Paclitaxel/carboplatin is a chemotherapy option for patients with advanced
      urothelial carcinoma and renal dysfunction. Future trials in chemotherapy
      development for this patient population are warranted.

PMID- 12209687
TI  - Metastatic prostate carcinoma to bone: clinical and pathologic features
      associated with cancer-specific survival.
AB  - BACKGROUND: The objective of this study was to examine the clinical and
      pathologic features of metastatic prostate carcinoma to bone in a large cohort of
      men, and the associations of these features with outcome. METHODS: Sixty-eight
      men who underwent surgery for metastatic prostate carcinoma to bone for
      stabilization of a pathologic fracture or impending fracture were studied.
      Clinical characteristics included the type of treatment for the primary and
      metastatic prostate carcinoma, age and serum prostate specific antigen (PSA) at
      the diagnosis of the metastatic prostate carcinoma, radiographic findings of the
      metastasis (osteoblastic, osteolytic, or mixed), and the number of metastatic
      sites at the time of the surgery for the metastasis. Pathologic features examined
      included Gleason score of the metastatic prostate carcinoma. Immunohistochemical
      stains for MIB-1, cytokeratin, PSA, synaptophysin, chromogranin A, serotonin,
      estrogen receptor, progesterone receptor, and androgen receptor were performed
      for all cases. The Kaplan-Meier method was used to estimate cancer-specific
      survival. The duration of follow-up was defined as the interval from the date of
      surgery for the metastasis to the date of death or last follow-up. Univariate and
      multivariate Cox proportional hazards models were fit to assess the features that
      were associated with death from prostate carcinoma. RESULTS: The average
      (standard deviation) time from the surgery for the metastasis to death from
      prostate carcinoma was 1.5 (1.9) years, ranging from 0 days to 10 years, with a
      median of 1 year. The estimated cancer-specific survival rates at 1 year, 2
      years, and 3 years were 54.3%, 28.8%, and 22.9%, respectively. Median cancer
      specific survival occurred at 1.1 years. After 4 years of follow-up, there were
      only seven patients left at risk for death from prostate carcinoma. Features that
      were found to be significantly associated with death from prostate carcinoma
      univariately included the interval between the diagnosis of metastasis and the
      surgery for metastasis (P < 0.001), androgen deprivation therapy before surgery
      for the metastasis (P = 0.002), presentation with metastasis (P = 0.003), the
      number of metastatic sites (P = 0.034), Gleason score of the metastasis (P =
      0.002), and tumor positivity for chromogranin A (P = 0.041). On multivariate
      analysis, the interval between the diagnosis of metastasis and the surgery for
      metastasis (P < 0.001), Gleason score of the metastasis (P < 0.001), and tumor
      positivity for chromogranin A (P = 0.009) were associated significantly with
      death from prostate carcinoma. CONCLUSIONS: Although cancer-specific survival for
      patients after surgery for prostate carcinoma metastatic to bone is poor,
      assessments of tumor differentiation of the metastasis and chromogranin A
      positivity provide prognostic information.

PMID- 12209688
TI  - Impact of undergoing prostate carcinoma screening on prostate carcinoma-related
      knowledge and distress.
AB  - BACKGROUND: Despite the ongoing controversy regarding the utility of prostate
      carcinoma (PCa) screening, the prevalence of asymptomatic men who participate in
      free PCa screening programs is on the rise. However, this increased awareness has
      not been associated with increased knowledge about the potential limitations of
      PCa creening. We conducted a prospective assessment to delineate men's
      motivations for undergoing screening and to determine the impact of screening on
      psychological distress and on men's knowledge about PCa screening. METHODS: We
      conducted two telephone interviews with a group of 136 men registered to undergo
      free PCa screening at two hospital-based sites. The first interview was conducted
      before screening and the second interview followed receipt of the screening
      results. Interviews assessed demographics and screening history, reasons for
      undergoing the current screening, cancer-related and general psychological
      distress, knowledge of risk factors for PCa, and knowledge of the benefits and
      limitations of screening. Only participants with normal screening results were
      included in these analyses. RESULTS: "Seeking peace of mind about prostate
      cancer" was rated as the most important reason for undergoing screening. PCa
      related distress decreased following receipt of a negative result (P < 0.01).
      Stratified analyses indicated that this was particularly true among younger men
      and African American men (both Ps < 0.001). Awareness of the benefits of
      screening was very high, but awareness of limitations was low, with fewer
      limitations reported following screening compared with prescreening (P < 0.01).
      Although awareness of the established risk factors improved following screening,
      controversial risk factors (i.e., those with limited empirical support) and
      factors that were unrelated to PCa risk were also rated as more important in the
      development of PCa than they were before screening (all Ps < 0.05). Therefore,
      the results may reflect that following screening, participants were simply more
      likely to endorse plausible risk factors, rather than actually reflecting an
      increase in participants' knowledge. CONCLUSIONS: These results suggest the
      importance of developing informed consent procedures and educational programs for
      the asymptomatic men who participate in free prostate screening programs each
      year, as the decision to be screened is being made without the benefit of a full
      understanding of the current state of medical knowledge about PCa screening.
      Until the definitive results of the Prostate, Lung, Colorectal, and Ovarian
      Cancer Screening Trial are available, improved patient education is needed to
      assist men in making screening decisions consistent with their own preferences.

PMID- 12209689
TI  - Thirteen-year, long-term efficacy of interferon 2alpha and interleukin 2-based
      home therapy in patients with advanced renal cell carcinoma.
AB  - BACKGROUND: The goal of the current report was to demonstrate the long-term
      efficacy of outpatient subcutaneous (sc) interferon alpha (IFN-alpha) and sc
      interleukin 2 (IL-2)-based combination regimens in patients with metastatic renal
      cell carcinoma. METHODS: In three consecutive clinical trials, 443 patients
      received combined sc IFN-alpha and sc IL-2 (n = 97 patients); combined sc IFN
      alpha, sc IL-2, and intravenous (iv) 5-fluorouracil (5-FU) (n = 260 patients); or
      combined sc IFN-alpha, sc IL-2, and iv 5-FU with oral 13cis-retinoic acid (n = 86
      patients). RESULTS: The median overall survival was 21+ months. The 2-year, 5
      year, and 13-year survival rates were calculated at 45.26%, 15.96%, and 8.96%,
      respectively. The median time to disease progression was 6 months. The 2-year, 5
      year, and 13-year progression free survival rates were 17.84%, 9.54%, and 9.20%,
      respectively. CONCLUSIONS: The current data suggest that combined outpatient sc
      IFN-alpha and sc IL-2, according to the Atzpodien regimen, achieves long-term
      survival benefits in a subset of patients with metastatic renal cell carcinoma,
      both with and without 13-cis-retinoic acid and/or 5-fluorouracil.

PMID- 12209690
TI  - Salvage combination chemotherapy with 5-fluorouracil and actinomycin D for
      patients with refractory, high-risk gestational trophoblastic tumors.
AB  - BACKGROUND: The objective of this study was to evaluate the efficacy and toxicity
      of a high-dose 5-fluorouracil and actinomycin D regimen (the FA regimen) as
      salvage chemotherapy for patients with high-risk gestational trophoblastic tumors
      (GTTs). METHODS: From 1985 to 1997, 10 patients with refractory, high-risk GTTs
      were treated with the FA regimen at Chiba University Hospital. Of those 10
      patients, 7 patients developed drug resistance to methotrexate, etoposide, and
      actinomycin D combination chemotherapy (the MEA regimen); 1 patient developed
      recurrent disease after receiving the MEA regimen; and 2 patients developed
      recurrent disease after receiving combination chemotherapy with etoposide,
      methotrexate, and actinomycin D alternating with cyclophosphamide and vincristine
      (the EMA/CO regimen). The hematologic toxicity of the FA regimen was graded at
      every chemotherapy course. RESULTS: With the FA regimen, the survival rate was
      80.0% (8 of 10 patients) for a mean follow-up of 10 years. Two patients died due
      to multidrug resistance, and two patients subsequently developed recurrent
      disease. The two patients with recurrent disease were successfully salvaged again
      with the MEA regimen. The toxicity of the FA regimen was evaluated in 78 cycles.
      Myelosuppression seemed to be the dose-limiting toxicity, and the incidences of
      World Health Organization Grade 4 leukocytopenia and thrombocytopenia were 6.4%
      and 3.8%, respectively, of 78 cycles. CONCLUSIONS: Although etoposide-containing
      chemotherapy is currently the most effective and well-tolerated regimen for
      patients with high-risk GTTs, 20-30% of patients develop resistance to etoposide
      containing regimens. Salvage combination chemotherapy with FA is effective for
      these patients with refractory disease, and the toxicity is predictable and
      manageable.

PMID- 12209691
TI  - Association of hypoxia-inducible factors 1alpha and 2alpha with activated
      angiogenic pathways and prognosis in patients with endometrial carcinoma.
AB  - BACKGROUND: Hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha are
      essential regulatory proteins for the adaptation of tumor cells to hypoxia, and
      they stimulate angiogenesis through activation of the vascular endothelial growth
      factor (VEGF) gene. METHODS: HIF-1alpha and HIF-2alpha proteins were studied
      immunohistochemically in a group of 81 patients with Stage I endometrial
      adenocarcinoma of the endometrioid cell type. The results were correlated with
      intratumoral angiogenesis, the expression of the angiogenic factors VEGF and
      thymidine phosphorylase (TP), and the VEGF/receptor (VEGF/KDR) complex. Relations
      also were sought with estrogen receptor (ER) and progesterone receptor (PR), with
      the apoptosis-related proteins bcl-2 and p53, with several histopathologic
      parameters, and with patient prognosis. In addition, a sample of 25 normal
      endometria at various phases of the menstrual cycle was studied for the presence
      of HIF-1alpha and HIF-2alpha. RESULTS: HIF-1alpha expression was detected in 49%
      of endometrial carcinomas. The expression was cytoplasmic or mixed
      nuclear/cytoplasmic. HIF-1alpha expression was associated with up-regulation of
      the VEGF pathway and with increased standard microvessel density (sMVD) and
      activated VEGF/KDR microvessel density (aMVD). It also was associated with a poor
      prognosis in both univariate and multivariate analyses. HIF-2alpha protein showed
      a pattern of expression similar to the pattern seen in HIF-1alpha, but expression
      of HIF-2alpha protein occurred in only 17% of endometrial carcinomas, and it was
      associated with increased TP reactivity. There also was a relation of HIF-1alpha
      expression with well-differentiated endometrial neoplasms, and there was a
      marginal association of HIF-1alpha and HIF-2alpha with ER expression. With
      reference to normally cycling tissues, HIF-1alpha nuclear/cytoplasmic expression
      was particularly strong in the samples of early proliferative phase endometrium
      compared with HIF-2alpha protein expression, which showed a constant reaction
      throughout the menstrual cycle. CONCLUSIONS: The up-regulation of HIF-1alpha and,
      to a lesser extent, of HIF-2alpha is a common event in Stage I endometrial
      adenocarcinomas. In these tumors, HIF-1alpha expression is related to increased
      angiogenesis, through activation of the VEGF angiogenic pathway, and to an
      unfavorable prognosis. HIF-2alpha accumulation is associated with increased
      expression of the angiogenic factor TP.

PMID- 12209692
TI  - Financial analysis of patients with newly diagnosed acute myelogenous leukemia on
      protocol or standard therapy.
AB  - BACKGROUND: Medicare and third-party payers may be reluctant to pay for
      investigational (protocol) therapy for patients with cancer on the premise that
      such treatment is more expensive than standard therapy. However, prior studies
      that have attempted to compare protocol therapy with standard therapy have been
      difficult to interpret because of the assortment of malignancies studied and the
      lack of suitable control groups of patients who received standard therapy.
      METHODS: In the current study, the authors conducted a retrospective review of
      the financial charges associated with protocol or nonprotocol (standard)
      chemotherapy in patients with a single malignancy, newly diagnosed acute
      myelogenous leukemia (AML), who received their initial course of chemotherapy
      ("induction") at the Memorial Sloan-Kettering Cancer Center (MSKCC) between 1996
      and 1999. Protocol and nonprotocol groups were analyzed according to clinical
      characteristics and standard prognostic features to determine whether the two
      groups were comparable. Median charges for all patients were determined using a
      database that linked clinical information, financial data, and clinical outcomes.
      RESULTS: A total of 353 patients with newly diagnosed AML were registered at
      MSKCC during the time period studied; of these, 79 patients (22%) received all of
      their care at the institution. Thirty patients (38%) received treatment on an
      investigational protocol. Forty-nine patients (62%) did not receive protocol
      therapy for the following reasons: 10 patients (20%) did not meet eligibility
      criteria, 4 patients (8%) were eligible for protocol therapy but declined, and 35
      patients (71%) met protocol criteria but were not offered protocol therapy based
      on the judgment of their primary oncologist. The groups were not comparable
      because patients treated with standard therapy were older and had a poorer
      initial Eastern Cooperative Oncology Group (ECOG) performance status. Overall
      median charges for patients in the nonprotocol group were higher than for
      patients treated on a protocol although charges were not related to age, initial
      ECOG performance status, or cytogenetic risk group. CONCLUSIONS: Although charges
      for the nonprotocol group were higher, specific factors responsible for this
      difference were not identified. This study emphasizes the problems inherent in
      assembling suitable groups of patients for comparison.

PMID- 12209693
TI  - Prognostic value of plasma interleukin-6 levels in patients with chronic
      lymphocytic leukemia.
AB  - BACKGROUND: Interleukin 6 (IL-6) is a B-cell growth and differentiation factor,
      which may promote the growth of B-cell neoplasms. In chronic lymphocytic leukemia
      (CLL) patients, IL-6 plasma levels increased in a stage-dependent manner,
      suggesting that IL-6 may be a useful prognostic marker. The purpose of this study
      is to fully assess the prognostic value of IL-6 in CLL patients. METHODS: We
      measured the plasma levels of IL-6 in 100 CLL patients using an enzyme-linked
      immunoassay method. RESULTS: Increasing levels of IL-6 significantly correlated
      with patient age, severity of anemia, Rai stage, white cell count, and beta-2
      microglobulin (beta-2M). Although CLL patients did not differ significantly from
      the normal controls in the median IL-6 plasma level (P = 0.38), patients with
      advanced diseases (defined by Rai stage III/IV or beta-2M > 3.5) had a
      significantly higher median IL-6 plasma level than the normal controls (P <
      0.05). Furthermore, in patients with advanced diseases, Cox regression hazards
      model showed that a higher IL-6 level correlated with shorter survival (P =
      0.0001). Using IL-6 level of 3 pg/mL as a cutoff, patients with low IL-6 levels
      had a significantly longer overall survival than those with high IL-6 levels (log
      rank test, P = 0.002). In patients with CD38-positive CLL, patients with high IL
      6 levels (> 3 pg/mL) had significantly shorter survival (P = 0.03). To conclude,
      IL-6 is a particularly useful predictor for survival in CLL patients with
      advanced diseases. CONCLUSIONS: Our findings suggest that patients with advanced
      stage CLL as well as high IL-6 plasma levels may require aggressive therapeutic
      approaches and special consideration for experimental therapy.

PMID- 12209694
TI  - High prevalence of endocrine dysfunction in long-term survivors after allogeneic
      bone marrow transplantation for hematologic diseases.
AB  - BACKGROUND: The progressively increasing number of long-term survivors after
      allogeneic bone marrow transplantation (allo-BMT) led researchers to focus on the
      early and late complications of this procedure. Endocrine dysfunction occurred
      mostly in patients who had undergone total body irradiation (TBI) as part of
      pretransplantation treatment. The extent to which chemotherapy and immune system
      derangement affect endocrine function in allo-BMT recipients is still unclear.
      METHODS: Forty consecutive patients (21 women, 19 men) with hematologic diseases
      surviving 12 or more months after allo-BMT from HLA-identical siblings were
      studied. Patients' age at transplantation ranged from 13 to 45 years and their
      post-BMT follow-up lasted 12-62 months. The conditioning regimen BUCY2 was
      employed. Graft versus host disease (GVHD) was observed in the acute form in 13
      patients and in the chronic form in 26. The function of hypothalamic-pituitary
      gonad, thyroid, somatotrophic, and adrenal axes was assessed. RESULTS: The most
      common endocrine dysfunction was ovarian insufficiency (95% of women), followed
      by an increase in follicle-stimulating hormone in 47% of men, indicating
      spermatogenesis damage. Hormone replacement therapy was contraindicated in three
      women because of chronic liver GVHD and it was ineffective partially in four
      others because of reduced intestinal or cutaneous absorption. Thyroid dysfunction
      occurred in 47.5% of patients and included low T3 syndrome, chronic thyroiditis,
      and transient subclinical hyperthyroidism and subclinical hypothyroidism. Adrenal
      function was abnormal in 10%, mostly related to the prolonged corticosteroid
      treatment. IGF-I was lower than age-reference values in 27% of all patients and
      in 38% of those with chronic GVHD. Thyroid, adrenal, and IGF-I impairments were
      more frequent in patients with chronic GVHD than in patients without this disease
      (P = 0.048). CONCLUSIONS: A high prevalence of endocrine dysfunction was detected
      in a cohort of allo-BMT recipients not treated by TBI. Although gonadal failure
      was likely related to intensive myeloablative treatments, thyroid, adrenal, and
      IGF-I impairments were late events, suggesting that immunosuppressive treatment
      and immune system derangement may play a role in the development of endocrine
      dysfunction after allografting.

PMID- 12209695
TI  - Predictive factors for suicidal ideation in patients with unresectable lung
      carcinoma.
AB  - BACKGROUND: Despite serious concern over the suicidality of cancer patients in
      clinical oncology practice, few studies have addressed this issue. The purpose of
      the current study was to investigate the prevalence and predictive factors of
      suicidal ideation in patients with unresectable lung carcinoma in a follow-up
      setting. METHODS: Patients with newly diagnosed unresectable nonsmall cell lung
      carcinoma participated in this study. Their suicidal ideation was assessed 6
      months after disclosure of the cancer diagnosis. Predictive factors for suicidal
      ideation were investigated by assessing a broad range of biomedical and
      psychosocial factors between the time of disclosure and start of cancer therapy
      (baseline) and 6 months after disclosure of the cancer diagnosis (follow-up).
      RESULTS: Although strong suicidal ideation was rare in this population, 13 (15%)
      of the 89 subjects who completed the baseline and follow-up ratings had some
      degree of suicidal ideation 6 months after disclosure of the cancer diagnosis.
      Univariate analysis revealed that significant predictive factors for suicidal
      ideation were pain at baseline, declining physical function, and the development
      of a depressive disorder. Multivariate analysis indicated that pain at baseline
      (odds ratio [OR] = 3.72, 95% confidence interval [CI] = 1.12-14.69, P = 0.04) and
      the development of a depressive disorder (OR =27.97, 95% CI = 5.18-214.14, P =
      0.0003) were the final significant predictive factors. CONCLUSIONS: Suicidal
      ideation among unresectable lung carcinoma patients should not be neglected
      because it is not rare. Comprehensive care consisting of at least earlier pain
      management and appropriate psychiatric intervention is indispensable to prevent
      subsequent suicidal ideation.

PMID- 12209696
TI  - Dermoscopic and histopathologic diagnosis of equivocal melanocytic skin lesions:
      an interdisciplinary study on 107 cases.
AB  - BACKGROUND: Dermoscopy (dermatoscopy, epiluminescence microscopy) is increasingly
      employed for the preoperative detection of cutaneous melanoma; dermoscopic
      features of pigmented skin lesions have been previously defined using
      histopathology as the key to the code. In a preliminary study on 10 cases
      evaluated by nine dermoscopists and nine histopathologists, the authors
      experienced that when at least two dermoscopists disagree in evaluating a
      melanocytic lesion, even histopathologic consultations may give equivocal
      results. METHODS: One hundred seven melanocytic skin lesions, consecutively
      excised because of equivocal clinical and/or dermoscopic features, were
      retrospectively examined by eight dermoscopists and eight histopathologists; the
      diagnostic interobserver agreement was calculated by means of the Schouten k
      statistics. After histopathologic consultations, all 107 lesions underwent
      unblinded dermoscopic re-evaluation in order to find which dermoscopic features
      had given rise to histopathologic diagnostic difficulties. RESULTS: The
      interobserver ageement was good for both dermoscopy (k = 0.53) and histopathology
      (k = 0.74). Out of 48 cases evaluated by the dermoscopists in complete
      accordance, only 8 (16.7%) received at least one conflicting histopathologic
      diagnosis. Instead, among the remaining 59 cases with at least one disagreeing
      dermoscopic diagnosis, 21 (35.6%) received at least one disagreeing
      histopathologic diagnosis. The unblinded dermoscopic re-evaluation showed that
      five out of seven lesions with clear-cut regression structures were
      histopathologically controversial. CONCLUSIONS: At least for selected and
      reasonably difficult lesions, a diagnostic discrepancy among formally trained
      dermoscopists seems to be predictive for a diagnostic disagreement among
      histopathologists. Lesions showing clear-cut regression structures are prone to
      give some histopathologic disagreement.

PMID- 12209697
TI  - Immunomodulatory effects of high-dose and low-dose interferon alpha2b in patients
      with high-risk resected melanoma: the E2690 laboratory corollary of intergroup
      adjuvant trial E1690.
AB  - BACKGROUND: The clinical antitumor activity of recombinant interferon alpha2b
      (IFNalpha2b) has been well documented in patients with advanced and high-risk
      melanoma; however, its mechanism of action remains conjectural. Trial E2690
      evaluated the immunomodulatory effects of IFNalpha2b in vivo during treatment at
      high doses (the HDI arm; n = 51 patients) and at low doses (the LDI arm; n = 54
      patients) in relation to standard observation (OBS; n = 43 patients). METHODS:
      This study evaluated peripheral blood lymphocytes (PBLs) for phenotypic markers
      and cytotoxic functions at 1 month, 3 months, and 12 months in the HDI arm, the
      LDI arm, and the OBS arm and examined correlations between changes observed in
      PBLs or in tumors with regard to treatment dosage and disease outcome. Tumor
      biopsy samples were studied for response to IFNalpha2b at a range of
      concentrations in vitro. RESULTS: Baseline blood phenotypic and functional assays
      did not predict disease outcome; however, modulation of these immunologic assays
      by IFNalpha2b treatment was observed and was associated with IFNalpha2b dosage.
      Tumor cell class II major histocompatibility antigen expression (human
      leukocyte/lymphocyte antigen DR) and adhesion molecule expression (ICAM-1) were
      modulated by exposure to IFNalpha2b in a dose dependent manner. Blood natural
      killer (NK) cell function, T-cell function, and subset distribution were
      modulated early by patients in the HDI arm and later by patients in the LDI arm.
      None of the variables tested in these studies predicted recurrence free survival.
      The numbers of patients studied were smaller than may be needed to detect
      potentially clinically significant changes. CONCLUSIONS: These data demonstrate
      changes in immunologic parameters associated with IFNalpha2b treatment and dosage
      that may account for some of the differences in the clinical efficacy of this
      modality. The current results also suggest the need for further study of newer
      molecular intermediates of IFNalpha2b and T-cell response to specific antigens of
      melanoma.

PMID- 12209698
TI  - Modulation of growth and radiochemosensitivity of human malignant glioma cells by
      acidosis.
AB  - BACKGROUND: Glioblastoma commonly is characterized by hypoxia and acidosis and
      the histologic features of tissue necrosis and neovascularization. Current
      approaches of adjuvant radiochemotherapy for patients with glioblastoma have only
      a modest impact on the natural course of this disease. METHODS: The authors
      examined the effects of acidosis on growth and response to irradiation and
      chemotherapy in cultured human malignant glioma cells. RESULTS: The authors found
      that mild acidosis (pH 7.0) inhibited the growth of cell lines that retained wild
      type p53 activity but did not inhibit the growth of cell lines that were devoid
      of p53 function. Transfer of a dominant-negative p53 gene into p53 wild type
      cells failed to override the acidosis-conferred growth arrest, suggesting that
      loss of p53 activity per se does not mediate escape from acidosis-induced growth
      inhibition. Moderate acidosis (pH 6.6) inhibited the growth of all cell lines.
      Acidosis-mediated growth arrest was not associated with a specific type of cell
      cycle arrest, e.g., in G0/G1 or G2/M phase. Acidosis did not result in consistent
      changes in radiosensitivity; however, it enhanced the cytotoxic effects of
      lomustine but conferred protection from topotecan, vincristine, teniposide, and
      cisplatin cytotoxicity. Lomustine exhibited enhanced stability at low pH,
      providing a putative mechanism for the enhanced cytotoxic effects of lomustine in
      acidotic conditions. Decreased sensitivity to the other drugs did not result from
      altered multidrug resistance drug transport activity. CONCLUSIONS: Taken
      together, the current results suggest that tissue acidosis may be an important
      determinant of glioma cell responses to adjuvant radiochemotherapy. The superior
      activity of nitrosoureas, such as lomustine, compared with other agents in
      patients with glioblastoma may result in part from prolonged drug stability in an
      acidotic microenvironment.

PMID- 12209699
TI  - Radiographic response to neoadjuvant chemotherapy is a predictor of local control
      and survival in soft tissue sarcomas.
AB  - BACKGROUND: Downstaging of large soft tissue sarcomas can be accomplished by the
      use of neoadjuvant chemotherapy (NeoCT). The authors tested the hypothesis that
      radiographic response to NeoCT predicts improved local control and survival.
      METHODS: The authors reviewed the medical records of 65 patients with Stage II or
      III soft tissue sarcoma (42 extremity, 23 retroperitoneal) who were treated with
      doxorubicin or ifosfamide-based NeoCT from January 1991 to December 1996.
      Radiographic response and impact on surgical therapy were determined
      retrospectively by comparing imaging studies obtained before and after
      chemotherapy. RESULTS: The radiographic responses observed were partial response
      (PR; 22 patients [34%]); minor response (MR; 6 patients [9%]); stable disease (20
      patients [31%]); and progressive disease (17 patients [26%]). Downstaging
      sufficient to decrease the scope of the operation occurred in 13% of the
      patients, 78% had no change, and 9% had disease progression sufficient to
      increase the scope of the operation. Patients having any radiographic response
      (PR or MR) had a higher margin-negative resection rate, a better local recurrence
      free survival rate, and a better overall survival rate than did nonresponders.
      CONCLUSIONS: The NeoCT regimens used in this study resulted in tumor shrinkage
      sufficient to impact surgical therapy in a few patients. However, radiographic
      response predicted improved local control and overall survival rate.

PMID- 12209700
TI  - Telomerase activity and human telomerase reverse transcriptase mRNA expression
      are correlated with clinical aggressiveness in soft tissue tumors.
AB  - BACKGROUND: Telomerase is a ribonucleoprotein enzyme that extends telomere
      specific repeats on the ends of chromosomes. Telomerase activity has been
      detected frequently in various types of human tumors and has been associated with
      cell immortality and oncogenesis. Human telomerase reverse transcriptase (hTERT),
      a telomerase catalytic subunit, reportedly regulates telomerase activity. Little
      is known about telomerase activity and hTERT mRNA expression in soft tissue
      tumors. The objective of this study was to clarify the correlation between these
      two parameters and clinical aggressiveness in soft tissue tumors. METHODS: In 41
      surgically resected soft tissue tumors, telomerase activity was measured by the
      fluorescence-based telomeric repeat-amplification protocol and hTERT mRNA
      expression was determined by real-time polymerase chain reaction. RESULTS:
      Telomerase activity was detected in 52% of sarcomas and in none of the benign
      soft tissue tumors (P < 0.05). Telomerase activity was found in 77% of 13 locally
      recurrent sarcomas and in 89% of 9 sarcomas with distant metastasis. The
      frequency of the presence of telomerase activity in those tumors was
      significantly greater compared with the frequency of telomerase activity in the
      other sarcomas (P < 0.05 and P < 0.01, respectively). All telomerase positive
      sarcomas expressed hTERT mRNA. The mean level of hTERT mRNA expression in
      sarcomas was significantly greater compared with the mean hTERT mRNA expression
      level in benign tumors (P < 0.05) and in locally recurrent sarcomas compared with
      primary sarcomas (P < 0.001). CONCLUSIONS: The results of the current study
      suggest that the detection of telomerase activity and the level of hTERT mRNA
      expression are useful markers for evaluating the clinical aggressiveness in soft
      tissue tumors.

PMID- 12209701
TI  - Physical activity across the cancer continuum: report of a workshop: review of
      existing knowledge and innovative designs for future research.

PMID- 12209702
TI  - Long-term results of reirradiation for patients with recurrent rectal carcinoma.
AB  - BACKGROUND: The current study was conducted to assess the long-term results of
      reirradiation in patients with recurrent rectal carcinoma. METHODS: One hundred
      and three patients with recurrent adenocarcinoma of the rectum underwent
      reirradiation with concurrent 5-fluorouracil-based chemotherapy. The initial
      radiation dose to the pelvis ranged from 3000 to 7400 centigrays (cGy) with a
      median dose of 5040 cGy. The median time from initial treatment to recurrence was
      19 months. Irradiation techniques consisted of two lateral fields with/without a
      posterior pelvic field to include recurrent tumor with a margin of 2-4 cm only.
      The reirradiation doses ranged from 1500 to 4920 cGy with a median dose of 3480
      cGy. Total cumulative doses ranged from 7060 to 1080 cGy with a median total dose
      of 8580 cGy. After the reirradiation, 34 patients also underwent surgical
      resection for residual disease. Fourteen patients underwent pelvic exenteration,
      11 patients underwent abdominoperineal resection, 4 patients underwent transanal
      transabdominal proctosigmoidectomy, 2 patients underwent full thickness local
      excision, and 3 patients underwent a Hartmann resection. RESULTS: Follow-up
      ranged from 3 84 months with a median follow-up of 2 years. The median survival
      for the whole group was 26 months and the 5-year actuarial survival rate was 19%.
      The median interval and 5-year survival rate of patients undergoing surgical
      resection after reirradiation was 44 months and 22% compared with 14 months and
      15% for patients treated with reirradiation only (P = 0.001). Treatment was
      generally well tolerated. Fifteen patients required a treatment break and early
      termination of treatment for Grade 3 and higher diarrhea, moist desquamation, or
      mucositis. Late complications were seen in 22 patients, including persistent
      severe diarrhea in 18 patients with 10 patients requiring long-term parental
      support, small bowel obstruction was seen in 15 patients, fistula formation in 4
      patients, and coloanal stricture in 2 patients. There was no difference in
      incidence of acute or long-term complications by the total radiation dose
      delivered. CONCLUSIONS: In patients with recurrent rectal carcinoma, high doses
      of reirradiation can be delivered with acceptable risks without prohibitive long
      term side effects. Surgical salvage and long-term survival of patients are
      possible.

PMID- 12209703
TI  - Current concepts in radiation enteritis and implications for future clinical
      trials.
AB  - BACKGROUND: Radiation enteritis is one of the most feared complications of
      abdominal and pelvic radiation. Once its occurs, the process is relentless and
      may result in the patient's death. Available treatment is only supportive. Recent
      progress in molecular biology has shed some light on the pathogenesis of
      radiation enteritis and other diseases that are characterized by excessive
      fibrosis. New treatment modalities may be devised to improve the outcome of
      patients who are affected with this complication. METHODS: A literature search
      was used to identify the common denominator between many radiation-induced
      fibrotic conditions and other sclerotic diseases. Factors that affect the disease
      process and possible therapeutic interventions were evaluated. RESULTS: The
      hyperstimulation of transforming growth factor beta1 (TGF-beta1) leads to
      increased fibrosis and, ultimately, organ failure. Interferon gamma (IFN-gamma)
      inhibits the effects of TGF-beta1 in the nucleus. The fibrotic process may be
      reverted by IFN-gamma in various pathologic conditions. CONCLUSIONS: Radiation
      enteritis and other radiation-induced, long-term complications are characterized
      by excessive stimulation of TGF-beta1. Preliminary studies suggest that IFN-gamma
      may be effective in the treatment of patients with radiation-induced cutaneous
      fibrosis. IFN-gamma should be considered in Phase I-II studies to assess its
      toxicity and efficacy in the treatment of patients with radiation enteritis.

PMID- 12209704
TI  - Dextromethorphan for the reduction of immediate and late postoperative pain and
      morphine consumption in orthopedic oncology patients: a randomized, placebo
      controlled, double-blind study.
AB  - BACKGROUND: Postoperative pain is mediated centrally by N-methyl-D-aspartate
      (NMDA) receptors. The beneficial effects of preincision oral dextromethorphan
      (DM), which is an NMDA antagonist, on postoperative pain and intravenous patient
      controlled analgesia (IV-PCA) morphine (MO) consumption have been examined in
      patients undergoing surgery. The authors investigated 75 patients who underwent
      surgery for bone and soft tissue malignancies, in whom postoperative pain is more
      severe compared with patients who undergo general surgery. METHODS: Patients
      received placebo, DM 60 mg, or DM 90 mg (25 patients per group) before surgery
      and on each of the two following days in a randomized, double-blind, placebo
      controlled manner. Postoperative IV-PCA MO was started when subjective pain
      intensity was >/= 4/10 (visual score) and lasted for 72 hours. Rescue drugs on
      demand were oral paracetamol or dipyrone. RESULTS: The patients in the DM60 and
      DM90 groups similarly experienced 50-80% less pain (P < 0.01) compared with
      patients in the placebo group, both immediately and up to 3 days postoperatively,
      as well as a 50% reduction in the estimated overall maximal pain intensity (P <
      0.01). Both DM groups consumed 50-70% less MO than the nonmedicated individuals
      in the placebo group (P < 0.01), and their demand for rescue drugs on the first
      postoperative day also was significantly lower (P < 0.01). Patients in the DM
      groups also were sedated less ( approximately 70%; P < 0.01). There were no
      differences among the groups in terms of when the patients left their beds, when
      they were discharged home, or the number of overall side effects. CONCLUSIONS: DM
      is associated with reduced pain intensity, sedation, and analgesic requirements,
      even in patients undergoing surgery for bone and soft tissue malignancies. A 3
      day DM administration neither increased the incidence of side effects nor
      accelerated ambulation and discharge home.

PMID- 12209705
TI  - Prodrug bioactivation and oncolysis of diffuse liver metastases by a herpes
      simplex virus 1 mutant that expresses the CYP2B1 transgene.
AB  - BACKGROUND: Herpes simplex virus 1 (HSV-1) infection of cancer cells results in
      viral replication with cell destruction and liberation of progeny virion that
      infect adjacent tumor cells. rRp450 is a novel replication-conditional HSV-1
      mutant that expresses both the endogenous herpes viral thymidine kinase gene and
      the rat p450 CYP2B1 transgene; p450 bioactivates such cancer prodrugs as
      cyclophosphamide. METHODS: Viral cytotoxicity and replication assays were
      performed in colon carcinoma cells as well as primary human hepatocytes. For in
      vivo studies, diffuse liver metastases were generated by inoculating MC26 cells
      into the portal system of BALB/c mice. Mice were treated with control media,
      rRp450, or rRp450 plus cyclophosphamide. RESULTS: Cytopathic effects induced by
      rRp450 replication in colon carcinoma cells were equivalent to those induced by
      wild type HSV-1 in vitro. Assays developed to separate cytotoxicity mediated by
      viral replication from cytotoxicity mediated by chemotherapy confirmed that HSV-1
      thymidine kinase bioactivates ganciclovir and CYP2B1 bioactivates
      cyclophosphamide in rRp450-infected cells. rRp450 mediated cytotoxicity in the
      presence of cyclophosphamide was increased by 21% to 30% above that achieved by
      viral replication alone. Cyclophosphamide bioactivation produced bystander
      killing of colon carcinoma cells but not hepatocytes. In contrast to these
      effects of cyclophosphamide, rRp450 mediated cytotoxicity was reduced in the
      presence of ganciclovir. These findings are explained by further experiments
      showing that bioactivation of cyclophosphamide only minimally affected HSV-1
      replication in colon carcinoma cells, whereas bioactivation of ganciclovir
      markedly attenuated HSV-1 replication. In vivo studies revealed a substantial
      decrease in hepatic tumor burden in all rRp450-treated animals compared to
      controls. The addition of cyclophosphamide augmented rRp450's in vivo anti
      neoplastic effect. CONCLUSIONS: The rRp450 mutant HSV-1 is highly oncolytic
      against colon carcinoma cells both in vitro and in vivo. rRp450 displays
      preferential replication in colon carcinoma cells compared to normal hepatocytes.
      Activation of cyclophosphamide by the p450 transgene augmented the anti
      neoplastic effects of rRp450 without simultaneously decreasing viral replication.
      Oncolysis induced by HSV-1 replication combined with cyclophosphamide prodrug
      activation warrants further investigation as a potential therapy for colon
      carcinoma liver metastases.

PMID- 12209706
TI  - Urinary calcium excretion in the monitoring of bone metastases from prostatic
      carcinoma.

PMID- 12209708
TI  - Treatment of micropapillary serous ovarian carcinoma (the aggressive variant of
      serous borderline tumors).

PMID- 12209709
TI  - Is micropapillary serous carcinoma for real?

PMID- 12209710
TI  - Pathobiology of preoperative chemotherapy: findings from the National Surgical
      Adjuvant Breast and Bowel (NSABP) protocol B-18.
AB  - BACKGROUND: Examination was performed on pathologic material from patients
      enrolled in the National Surgical Adjuvant Breast Project (NSABP) protocol B-18,
      in which the clinical effects of preoperative (preop) and postoperative (postop)
      doxorubicin and cyclophosphamide (AC) were compared. METHODS: Of the total number
      of 1523 patients, 1234 patients (81%) were in the pathologically evaluable
      cohort. Six hundred twenty-six patients had been randomized prospectively to
      receive AC postop and 608 had been randomized to receive AC preop. Preentry
      diagnosis was made by fine-needle aspiration (FNA) and/or Tru-cut biopsy (TC). AC
      induced and other pathologic changes were identified, and their relation to
      pathologic response and overall survival (OS) and disease-free survival (DFS) was
      determined. Frequencies of the number of lymph node metastases, their size,
      stromal reaction, and extracapsular extension (ECE) were compared in the two
      treatment groups, as was their correlation with OS and DFS. Survival estimates
      were based on 9 years of follow-up. RESULTS: Approximately 13% of primary breast
      carcinoma cases exhibited both a clinical complete response (cCR) and a
      pathologic complete response (absence of invasive tumor [pCR]) to preop AC. An
      additional 7% of patients exhibited a pCR in the absence of a cCR. A pCR occurred
      in 38% of those patients determined to have achieved a cCR. Poor nuclear grade of
      the tumor cells in the pre-entry FNA and/or TC specimens significantly predicted
      a pCR. Patients with the latter exhibited a better OS and DFS compared with those
      with a pathologic partial response (presence of sparse invasive tumor [pPR]) or
      no pathologic response (pNR). Epithelial alterations considered to be induced in
      tumors by preop AC were comprised of types 1 and 2 giant cells with meganuclei,
      apocrine metaplasia, and cytoplasmic vacuolation. They had a high degree of
      specificity (range, 86-99%) but a low sensitivity (range, 7-38%). All were
      predictive of a pPR and were found to be related adversely to OS and DFS. A
      fibrous stromal reaction noted in tumors or their putative sites in the preop
      group was found to have only modest degrees of specificity (63%) and sensitivity
      (74%). Moderate/marked sclerosis of basement membranes of the ductal and ductular
      elements of the terminal ductolobular unit (TDLU) was significantly more frequent
      in nontumor-bearing areas of breasts from patients in the preop treatment group
      compared with those in the postop treatment group (67% vs. 48%; P < 0.0001). The
      degrees of change in the TDLU in patients in the postop treatment group were
      found to be unrelated to age. Lymphatic tumor extension in the primary tumor, as
      well as a positive lymph node status, were less frequent in the preop treatment
      group compared with the postop treatment group. The OS and DFS were nearly
      identical in both treatment groups, being 69% and 55% and 70% and 53% in the
      preop and postop treatment groups, respectively, at 9 years. A fibrous stromal
      response to lymph node metastases was found to be significant for DFS but not OS.
      ECE was similar in both groups (55% vs. 48%; P = 0.12). Only 1% of ECE was found
      to be related to axillary failure in both treatment arms combined. There was no
      significant difference with regard to the parameters of survival for patients in
      the postop treatment group whose lymph nodes contained micrometastases (< 2.0 mm)
      or mini micrometastases (< 1.0 mm) (the latter detected immunohistochemically
      with anticytokeratin), and a true-negative lymph node status (not
      immunohistochemically converted to positive). Conversely, there was no apparent
      difference with regard to OS in preop treated patients with lymph node
      micrometastases, mini micrometastases, and macrometastases (P = 0.19). Those with
      mini micrometastases had a significantly worse OS compared with those with a true
      negative lymph node status (P = 0.0007). DFS remained worse for patients in that
      treatment group with micrometastases and mini micrometastases compared with those
      with negative lymph nodes, although it was better than that for patients with
      macrometastases (P = 0.02). CONCLUSIONS: Poor nuclear grade of tumor cells in the
      preentry FNA or TC specimens in the preop group was predictive of a pCR. AC
      induced meganuclear giant cells and apocrine changes and nuclear and histologic
      grades of the primary tumors also were found to be prognostically significant in
      patients in the preop treatment group, and the latter two variables were found to
      be significant for those patients in the postop treatment group. No evidence was
      found to support the need for axillary lymph node radiation for ECE of lymph node
      metastases. Extended pathologic or immunohistochemical procedures also appear to
      be unnecessary for the detection of lymph node mini micrometastases, at least
      when traditional postop chemotherapy is used. The adverse relation between such
      small metastases and OS and DFS after preop AC appears to be related to the
      timing of the chemotherapy administration rather than any pathobiologic reasons.

PMID- 12209711
TI  - Concurrent cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy and
      radiotherapy for breast carcinoma: a well tolerated adjuvant regimen.
AB  - BACKGROUND: The current study was conducted to assess the toxicity of concurrent
      adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy
      and radiotherapy (RT) for early breast carcinoma. METHODS: In the current study,
      the authors reviewed the records of 680 consecutive breast carcinoma patients who
      received adjuvant CMF at the Princess Margaret Hospital between 1980-1990.
      Surgery was comprised of mastectomy in 64% of patients, breast conservation in
      35% of patients, and was unknown in 1% of patients. Two hundred two patients
      received concurrent CMF/RT that was defined as an overlap in CMF and RT
      administration of at least 21 days. Forty-seven patients received sequential
      CMF/RT (defined as no overlap or an overlap of < 7 days in CMF and RT
      administration). Other patients received CMF alone. Adverse effects of RT were
      graded retrospectively using the Radiation Therapy Oncology Group (RTOG)/European
      Organization for Research and Treatment of Cancer (EORTC) system. Reasons for
      interruption or failure to complete RT were recorded. The magnitude of
      chemotherapy dose reductions and delays also were noted. RESULTS: The median age
      of the patients was 44 years (range, 26-68 years) and 88% of the patients had
      lymph node-positive disease. RT was interrupted or discontinued due to side
      effects in 4% of patients (95% confidence interval [95% CI], 1.7-7.7%) and 0%
      (95% CI, 0-7.6%), respectively, of the concurrent and sequential groups (P =
      0.36). The incidence of Grade 3 or Grade 4 RT toxicity was 1.5% (95% CI, 0.3
      4.3%) and 2.1% (95% CI, 0.1-11.3%), respectively, for the concurrent and
      sequential groups (P = 0.57). The median relative dose intensity of chemotherapy
      for patients receiving concurrent CMF/RT, sequential CMF/RT, and CMF alone was
      0.87, 0.84, and 0.85, respectively (P = 0.22). CONCLUSIONS: The results of the
      current study demonstrate that the concurrent administration of CMF and RT is
      associated with a low risk of serious toxicity and is an acceptable adjuvant
      regimen for patients with breast carcinoma.

PMID- 12209712
TI  - Provider case volume and outcome in the evaluation and treatment of patients with
      mammogram-detected breast carcinoma.
AB  - BACKGROUND: Practice volume may affect the outcome of patients with breast
      carcinoma. Defining factors that influence the relation of volume and outcome for
      the diagnosis and treatment of breast carcinoma is important, because breast
      carcinoma is common, and care is decentralized. METHODS: Community-wide diagnosis
      and treatment of mammogram-detected breast carcinoma was examined using claims
      data from a single insurer representing 25% of the regional population. Among
      1001 mammogram-directed breast biopsies, the rate of breast carcinoma diagnosed
      by stereotactic core needle biopsy (SCNB) or excisional biopsy with needle
      localization (EBNL) and the rate at which breast-conserving surgery (BCS) was
      used were analyzed. Outcome and practice volume were examined for surgeons,
      radiologists, and medical centers. RESULTS: Two hundred twenty-four tumors were
      diagnosed by EBNL (604 diagnoses) and SCNB (397 tumors), for a 22.4% positive
      biopsy rate. The median number of procedures per physician was one. Positive
      biopsy rates for radiologists, surgeons, and medical centers did not correlate
      with practice volume. Positive biopsy rates for high-volume physician providers
      and medical centers ranged from 9% to 46%. The BCS rate was 45% and 64% for
      surgeons treating one or more than one claim, respectively. Tumor stage and
      surgeon case volume were the only independent predictors of BCS (P < 0.05).
      CONCLUSIONS: There is wide variation in diagnosis and treatment outcomes for
      patients with mammogram-detected breast carcinoma. Overall, practice volume was
      correlated with the use of BCS but not with the rate of positive biopsy. A wide
      variation in the positive biopsy rate among high-volume providers and medical
      centers suggests that volume of practice is not a surrogate for quality in the
      diagnosis of breast carcinoma.

PMID- 12209713
TI  - Predicting the survival of patients with breast carcinoma using tumor size.
AB  - BACKGROUND: Tumor size has long been recognized as the strongest predictor of the
      outcome of patients with invasive breast carcinoma, although it has not been
      settled whether the correlation between tumor size and the chance of death is
      independent of the method of detection, nor is it clear how tumor size at the
      time of treatment may be translated into a specific expectation of survival. In
      this report, the authors provide such a method. METHODS: A Kaplan-Meier survival
      analysis was carried out for a population of 1352 women with invasive breast
      carcinoma who were treated at the Van Nuys Breast Center between 1966 and 1990,
      and the data were analyzed together with survival data published by others.
      RESULTS: The authors found that the survival of patients with invasive breast
      carcinoma was a direct function of tumor size, independent of the method of
      detection. The results showed that the correlation between tumor size and
      survival was well fit by a simple equation, with which survival predictions could
      be made from information on tumor size. For example, a comparison of three large
      populations studied over the last 5 decades revealed a marked improvement
      (approximately 35% absolute) in the survival of patients with invasive breast
      carcinoma diagnosed on clinical grounds that could be ascribed to a reduction in
      tumor size. However, the capacity of screening mammography to find smaller tumors
      remains the best way reduce breast carcinoma deaths, with the potential for
      adding an additional approximately 20% absolute reduction in breast carcinoma
      deaths. The mathematic correlation between tumor size and survival is consistent
      with a biologic mechanism in which lethal distant metastasis occurs by discrete
      events of spread such that, for every invasive breast carcinoma cell in the
      primary tumor at the time of surgery, there is approximately a 1-in-1-billion
      chance that a lethal distant metastasis has formed. CONCLUSIONS: The correlation
      between tumor size and lethality is well captured by a simple equation that is
      consistent with breast carcinoma death as the result of discrete events of
      cellular spread occurring with small but definable probabilities.

PMID- 12209714
TI  - Childhood and adolescent thyroid carcinoma.
AB  - OBJECTIVES: This analysis was performed to evaluate the influence of clinical and
      treatment factors on local tumor control, control of distant metastasis,
      survival, and complications in children and adolescents with thyroid carcinoma.
      METHODS: The records of 56 children and adolescents with papillary and follicular
      carcinoma of the thyroid were reviewed. They ranged in age from 4 to 20 years.
      There were 43 females and 13 males. At diagnosis, 15 (27%) patients had disease
      confined to the thyroid, 34 (60%) had additional lymph node metastasis to the
      neck or upper mediastinum, and 7 (13%) also had lung metastasis. Treatment
      consisted of a total thyroidectomy in 48 patients, a subtotal thyroidectomy in 4
      patients, and a lobectomy in 4 patients. All 56 patients received postoperative
      thyroid hormone suppressive therapy. (131)I was administered to 82% (46 of 56) of
      patients after their initial surgery. RESULTS: The overall survival rate was 98%
      with a follow-up of 0.6-30.7 years (with a median follow-up of 11.0 years). The
      one death that occurred in this patient population was the result of a congenital
      heart defect and was unrelated to thyroid carcinoma. The 10-year progression-free
      survival rate was 61%. Nineteen patients (34%) experienced a recurrence of their
      thyroid carcinoma. The time to first recurrence of disease ranged from 8 months
      to 14.8 years (mean, 5.3 years). None of those with disease confined to the
      thyroid developed recurrent disease. The recurrence rate was 50% (17 of 34) in
      patients with lymph node metastasis and 29% (2 of 7) in patients with lung
      metastasis (P = 0.02). Tumor characteristics were evaluated for time to first
      recurrence utilizing the logistic likelihood ratio test to predict disease
      recurrence. Thyroid capsule invasion (P = 0.02), soft tissue invasion (P = 0.03),
      positive margins (P = 0.006), and tumor location at diagnosis (thyroid only vs.
      thyroid and lymph nodes vs. thyroid, lymph nodes, and lung metastasis, P = 0.02)
      were significant for developing recurrent disease. Patients younger than 15 years
      old at diagnosis were more likely to have more extensive tumor at diagnosis than
      patients who were 15 years and older (thyroid only vs. thyroid and lymph nodes
      vs. thyroid, lymph nodes, and lung metastasis, P = 0.02). CONCLUSION: Carcinoma
      of the thyroid in children and adolescents has little risk of mortality but a
      high risk of recurrence. Younger patients present with a more advanced stage of
      disease and are more likely to have disease recurrence. Total thyroidectomy and
      lymph node dissection, followed by postoperative (131)I therapy, thyroid hormone
      replacement (suppressive) administration, and diligent surveillance are
      warranted.

PMID- 12209715
TI  - Hepatic vascular isolation and perfusion for patients with progressive
      unresectable liver metastases from colorectal carcinoma refractory to previous
      systemic and regional chemotherapy.
AB  - BACKGROUND: Many patients with colorectal carcinoma develop unresectable
      metastases confined to the liver that remain the life-limiting component of
      disease despite best available systemic or regional chemotherapy. In the current
      study, the authors present their results using vascular isolation and perfusion
      of the liver for individuals with progressive, unresectable liver metastases from
      colorectal carcinoma that were refractory to both previous systemic and regional
      chemotherapy. METHODS: Seven patients with refractory, progressive, unresectable
      colorectal carcinoma metastases confined to the liver underwent a 60-minute
      hyperthermic (39-40 degrees C) isolated hepatic perfusion (IHP) and were followed
      for toxicity, response, and survival. RESULTS: There was no surgical- or
      treatment-related mortality; all patients experienced transient Grade 3-4
      (according to National Cancer Institute common toxicity criteria) hepatic
      toxicity. At a median potential follow-up of 16 months, the overall objective
      radiographic response rate (all partial responses) was 71% (5 of 7 assessable
      patients). It is interesting to note that two patients who were treated with
      tumor necrosis factor (TNF) alone demonstrated no response to therapy compared
      with all five patients who were treated with melphalan and TNF (three patients)
      or melphalan alone (two patients). For the 5 patients who responded to treatment,
      the median duration of response was 10 months (range, 10-13 months) and in all 7
      patients the mean overall survival was 19.7 months (range, 2-33 months),
      including 5 months and 7.5 months, respectively, for the 2 patients treated with
      TNF alone. CONCLUSIONS: The results of the current study demonstrate that IHP
      using melphalan with or without TNF has significant antitumor activity in this
      patient population. IHP deserves continued clinical evaluation as a therapeutic
      modality for patients with unresectable colorectal carcinoma metastases to the
      liver.

PMID- 12209716
TI  - Decreased Smad4 expression in the transforming growth factor-beta signaling
      pathway during progression of esophageal squamous cell carcinoma.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta) has antiproliferative
      effects in various cells, and inactivation of the TGF-beta signaling pathway
      contributes to tumor progression or development. Smad4, a tumor suppressor gene,
      is a central mediator in the signaling pathways of the TGF-beta superfamily. This
      study was undertaken to clarify the correlation between Smad4 expression and the
      clinicopathologic characteristics of patients with esophageal squamous cell
      carcinoma (SCC). The authors also investigated the expression of components of
      the TGF-beta signaling pathway in seven established cell lines derived from
      esophageal SCC. METHODS: Immunohistochemistry for Smad4 using monoclonal anti
      Smad4 antibody was performed on surgical specimens obtained from 80 patients with
      esophageal SCC. In seven cell lines, the authors examined the expression of
      components of the TGF-beta signaling pathway using Western and Northern blot
      analyses. RESULTS: There was a significant inverse correlation between Smad4
      expression and both depth of invasion (P = 0.0008) and pathologic stage (P =
      0.0079). The expression of Smad4 proteins could be detected in five of seven cell
      lines. The expression of TGF-beta type II receptor protein was decreased in two
      of seven cell lines, and the expression of both Smad2 and Smad3 proteins was
      decreased in only one cell line. The level of expression of Smad4 mRNA did not
      differ dramatically between cell lines and was not correlated with the quantity
      of Smad4 protein. CONCLUSIONS: In this study, the expression of Smad4 protein
      appeared to be correlated with the depth of invasion of esophageal SCC. The loss
      of Smad4 expression was not regulated at the level of transcription.

PMID- 12209717
TI  - Gastric carcinoma: pathology findings in a multiethnic population.
AB  - OBJECTIVES: To assess the pathology of gastric carcinoma and to determine whether
      carcinoma of the cardia occurs more often among whites than among other ethnic
      groups in Hawaii. This study focuses on demographic differences in subsite
      locations and histologic types of gastric carcinoma. METHODS: We reviewed 532
      sequential gastric carcinomas accessioned between 1993 and 1999 in the Hawaii
      Tumor Registry. Pathology reports and slides were reviewed by the study
      pathologist. RESULTS: Carcinoma of the cardia occurred in 51 (15.8%) of 323 males
      compared with 18 (8.6%) of 209 females (P = 0.02, after age adjustment). The age
      adjusted percent of cardia cases was 41.8% for Hawaiian white males compared with
      13.4% for men of all other ethnic groups (P = 0.0002). The age-adjusted percent
      of cardia cases was 22.4% for Hawaiian white females compared with 7.3% for
      females of other groups. (P = 0.08). At all age levels, females had more frequent
      diffuse carcinomas and less frequent intestinal type gastric carcinomas than men.
      The age-adjusted percent with diffuse carcinoma was 35.3% for females and 13.7%
      for males (P < 0.0001). Also, the sex-adjusted percent with diffuse carcinoma was
      26.0% for patients younger than 75 years of age compared with 17.0% for patients
      75 years or older (P = 0.01). Conversely, the sex-adjusted percent with
      intestinal carcinoma was 67.9% for patients younger than 75 years of age compared
      with 77.1% for patients 75 years or older (P = 0.02). The proportion of cases
      showing precursor lesions (intestinal metaplasia or superficial gastritis)
      increased progressively with the distance of the carcinoma from the cardia.
      CONCLUSIONS: Carcinoma of the cardia is predominantly a tumor of white males and
      is not associated with the multifocal gastritis characteristically found with
      carcinoma distal to the cardia. Diffuse gastric carcinoma shows no ethnic
      predilection, but expression of this phenotype is clearly related to the age and
      gender of the patient.

PMID- 12209718
TI  - Pretreatment prognostic factors for survival in patients with advanced urothelial
      tumors treated in a phase I/II trial with paclitaxel, cisplatin, and gemcitabine.
AB  - BACKGROUND: New chemotherapeutic agents, including paclitaxel and gemcitabine,
      are active in advanced bladder carcinoma, and combination regimens with these
      agents have shown promising results. Unlike conventional chemotherapy regimens,
      such as methotrexate, vinblastine, doxorubicin, and cisplatin, there are no data
      available on key predictive factors for response and survival with these novel
      agents. Since this information is needed for selection of patients for these new
      combinations and for stratification purposes in ongoing randomized trials, the
      authors aimed to study the predictive factors for response and survival to the
      current regimen containing cisplatin, paclitaxel, and gemcitabine. METHODS: The
      authors studied 56 patients with advanced urothelial tumors treated on a Phase
      I/II trial of paclitaxel, cisplatin, and gemcitabine (TCG) to identify
      pretreatment characteristics that were prognostic for survival using this novel
      combination. The pretreatment characteristics analyzed were age, gender, Eastern
      Cooperative Oncology Group performance status, histopathology (pure transitional
      versus other), visceral (liver, lung, or bone) metastasis, number of sites of
      disease, lactate dehydrogenase, and hemoglobin. RESULTS: The factors that were
      associated with a worse survival in univariate analysis were performance status >
      0, presence of visceral metastasis, and more than one site of malignant disease.
      In a multivariate model, performance status (P = 0.044) and visceral disease (P =
      0.008) showed independent statistical significance for decreased survival.
      Patients were then grouped based on these two independent prognostic factors.
      Median survival times in the groups of patients with zero, one, or two of these
      risk factors were 32.8 months, 17 months, and 9.6 months, respectively (P =
      0.0005). CONCLUSIONS: A pretreatment performance status > 0 and the presence of
      visceral metastasis have a profound impact on survival when using the TCG
      regimen. These two variables will be used to stratify patients in the upcoming
      Phase III randomized trial comparing this TGC regimen with a
      gemcitabine/cisplatin regimen in advanced urothelial tumors.

PMID- 12209719
TI  - A pilot study of thalidomide in patients with progressive metastatic renal cell
      carcinoma.
AB  - BACKGROUND: The highly vascular nature of renal cell carcinoma (RCC) suggests
      that angiogenesis inhibition may be therapeutic for patients with this disease.
      Thalidomide inhibits basic fibroblast growth factor and vascular endothelial
      growth factor (VEGF)-induced angiogenesis. METHODS: In a pilot study, we
      evaluated the safety and efficacy of escalating doses of thalidomide in patients
      with progressive metastatic RCC (mRCC), measurable disease, and good organ
      function. Patients received oral thalidomide starting at 200 mg per day and
      increasing by 100-200 mg per day weekly until a target dose of 1200 mg per day
      was reached. Study endpoints were objective tumor response and toxicity. RESULTS:
      Of the 20 patients enrolled, 19 were evaluable for response. Eighteen achieved
      the target dose. The most common, but reversible, toxicities were constipation,
      somnolence, and fatigue. Peripheral neuropathy was seen after prolonged therapy,
      necessitating dose reduction. Two patients achieved a partial response and nine
      had stable disease for a median of 14 months (range, 3-17 months). Median time to
      progression was 4.7 months (range, 0.7-31.3 months). Fifteen patients died
      (median survival, 18.1 months; 95% lower confidence bound 10.7). Survival was
      significantly longer in patients with higher hemoglobin level and longer time
      from first metastasis to start of thalidomide, but significantly shorter in
      patients with multiple organ involvement and previous treatments. CONCLUSIONS:
      Thalidomide at this dose is associated with manageable acute toxicities but long
      term dose-limiting neuropathy. Objective responses are rare in patients with mRCC
      and are characterized by delay in achieving maximum tumor reduction. Prolonged
      stable disease is seen in some patients, but the benefit of thalidomide, as well
      as other angiogenesis inhibitors, in that setting needs to be studied in
      controlled, randomized trials.

PMID- 12209720
TI  - Extragonadal germ cell tumors in Taiwan: an analysis of treatment results of 59
      patients.
AB  - BACKGROUND: Extragonadal germ cell tumors (EGCT) are rare. They are biologically
      distinct from their testicular counterparts. Information regarding these tumors
      from the Far East is limited. More investigations are warranted to define the
      optimal treatment. METHODS: Retrospective review of the medical records of 59
      patients with EGCT treated between 1983 and 2001 at a large, tertiary care
      institute in Taipei. RESULTS: The study population comprised 54 males and 5
      females, ranging in age from 1 to 68 years old (median age, 21 years). Primary
      tumors occurred in the mediastinum (n = 27), retroperitoneum (n = 6), central
      nervous system (CNS; n = 24), and other sites (n = 2). Patients received surgery,
      chemotherapy, radiotherapy, or a combination of treatment modalities as the
      primary treatment. Three patients with mediastinal seminoma achieved complete
      remission (CR) and are alive with no evidence of disease (NED), with a median
      follow-up of 118 months. Of 24 patients with mediastinal nonseminomas, 8 (33%)
      are alive with a median disease-free survival (DFS) period of 33 months. Two of
      six patients with retroperitoneal nonseminomas obtained CR and are alive with NED
      at 41 and 110 months, respectively. Of 24 patients with intracranial germ cell
      tumors, 16 had germinoma and 13 (81%) achieved CR with NED at 8-228 months
      (median duration, 104 months). Four of eight patients with CNS nongerminomas
      remain in CR and are alive with a median DFS period of 48 months. Four patients
      with mediastinal nonsemonimas treated with salvage chemotherapy died.
      CONCLUSIONS: The treatment results of our patients with seminomatous EGCT are
      comparable to those of Western countries. However, the treatment results of
      patients with nonseminomatous EGCT are not as good. The reason for this
      discrepancy needs to be explored for a better treatment outcome of for patients
      in Taiwan with EGCT.

PMID- 12209721
TI  - Association of overexpressed proline-directed protein kinase F(A) with
      chemoresistance, invasion, and recurrence in patients with bladder carcinoma.
AB  - BACKGROUND: It has been shown previously that proline-directed protein kinase
      F(A) (PDPK F(A)) is overexpressed in various human malignancies compared with its
      expression in normal controls, and the suppression of overexpressed PDPK F(A) is
      capable of inhibiting the growth of various types of human carcinoma cells,
      suggesting a role for this PDPK in human malignancies. In this report, the
      authors combine immunohistologic, molecular, cellular, and clinicopathologic
      studies to demonstrate further an essential critical role for overexpressed PDPK
      F(A) in bladder carcinoma invasion, chemoresistance, and poor prognosis. METHODS:
      The expression and localization of PDPK F(A) were analyzed by the
      immunohistochemical staining of specimens obtained from patients with primary
      transitional cell carcinoma (TCC) of the bladder. The stable antisense clones of
      human bladder carcinoma cells with specific suppression of overexpressed PDPK
      F(A) were established for invasion and chemosensitivity studies. RESULTS: The
      immunohistochemical study revealed that PDPK F(A) was overexpressed
      preferentially in the invasive bladder carcinoma tissues. It was found that the
      stable antisense clones with specific suppression of overexpressed PDPK F(A) to
      approximately 40% of the parental control level were capable of inhibiting the
      invasive activity and simultaneously enhancing the chemosensitivity of bladder
      carcinoma cells to various therapeutic drugs, such as vinblastine, vincristine,
      paclitaxel, and bleomycin. Clinicopathologic studies also revealed a correlation
      between overexpressed PDPK F(A) and disease recurrence/survival in patients with
      primary TCC (P < 0.05). CONCLUSIONS: Taken together, the results demonstrate an
      essential critical role of overexpressed PDPK F(A) in invasion, chemoresistance,
      and poor prognosis. Suppression of overexpressed PDPK F(A) may provide a new
      potential target for therapeutic intervention aimed at preventing
      chemoresistance, disease progression, and recurrence in patients with bladder
      carcinoma.

PMID- 12209722
TI  - Proliferative activity is the most significant predictor of recurrence in
      noninvasive papillary urothelial neoplasms of low malignant potential and grade 1
      papillary carcinomas of the bladder.
AB  - BACKGROUND: Recurrence of transitional cell carcinoma of the bladder cannot be
      predicted accurately by traditional criteria alone. This study examined the value
      of cell proliferative activity, morphometry, and expression of p53, c-erbB-2, and
      bcl-2 oncogenes in predicting recurrence of superficial papillary urothelial
      neoplasms of low malignant potential (LMP) and Grade 1 (G1) papillary carcinomas
      of the bladder. METHODS: Sixty-two patients (mean age, 62 years) with newly
      diagnosed superficial pTa bladder tumors (19 LMP, and 43 G1) were analyzed
      retrospectively. All patients underwent transurethral resection (TUR). Median
      follow-up was 69 months. Serial sections from formalin-fixed, paraffin-embedded
      material at initial TUR were stained with monoclonal antibodies (MoAbs) DO7,
      CB11, and bcl-2-124. Cell proliferation was assessed by MIB-1 MoAb, the quantity
      of argyrophilic nucleolar organizer region-associated proteins (AgNORs), and
      mitotic count. RESULTS: Of the 62 patients, 42 (67.7%) had one or more
      recurrences. Recurrence rates were higher in MIB-1 (P < 0.0001) and p53
      immunopositive cases (P = 0.02), when the mitotic count was greater than 5 (P =
      0.004), and in G1 carcinomas (P = 0.04). In univariate analysis, the disease-free
      period was shorter for MIB-1 (P < 0.0001) and p53 immunopositive (P = 0.0001)
      cases, for cases with high AgNOR quantity (P = 0.04), mitotic count greater than
      5 (P = 0.01), and in G1 carcinomas (P = 0.002). In multivariate analysis, only
      MIB-1 immunoreactivity retained independent prognostic significance. CONCLUSIONS:
      Despite the small cohort, the results confirm the prognostic value of cell
      proliferation and p53 expression in patients with bladder neoplasms. The results
      also indicate that MIB-1 immunopositivity is the most significant predictor of
      recurrence and disease-free survival in superficial LMP and G1 papillary bladder
      carcinomas.

PMID- 12209723
TI  - Recurrent micropapillary serous ovarian carcinoma.
AB  - BACKGROUND: The objectives of the current study were to: 1) characterize the
      clinical outcome of patients with recurrent micropapillary serous ovarian
      carcinoma (MPSC) and 2) evaluate the survival impact of secondary cytoreductive
      surgery and other prognostic variables. METHODS: Twenty-six patients with
      recurrent MPSC were identified retrospectively from hospital and tumor registry
      databases. Survival curves were generated from the time of tumor recurrence using
      the Kaplan-Meier method and statistical comparisons were performed using the log
      rank test, logistic regression analysis, and the Cox proportional hazards
      regression model. RESULTS: The median age of the patients at the time of
      recurrence was 46 years. The mean progression-free interval was 31.6 months, and
      92% of patients had advanced stage disease at the time of the initial diagnosis.
      Twenty-one patients underwent secondary cytoreductive surgery; tumor debulking
      was performed in 90.5% of cases and 52.4% of patients required an intestinal
      resection. Optimal resection (residual disease < or = 1 cm) was achieved in 15
      patients (71.4%). Patients undergoing optimal secondary cytoreduction had a
      median survival time of 61.2 months from the date of disease recurrence, compared
      with 25.5 months for those patients in whom suboptimal residual disease remained
      (P < 0.02) and 29.9 months for nonsurgical patients (P < 0.01). On multivariate
      analysis, optimal secondary cytoreduction was found to be the only independent
      predictor of survival. Salvage chemotherapy produced an objective response in 25%
      of patients with measurable disease. The administration of chemotherapy prior to
      surgical intervention was associated with a trend toward worse survival and a
      lower likelihood of optimal secondary cytoreduction. CONCLUSIONS: Optimal
      secondary cytoreductive surgery is feasible in the majority of patients with
      recurrent MPSC and is an independent predictor of subsequent survival. Surgical
      intervention should be considered for those patients with recurrent MPSC. [See
      editorials on pages 675-6 and 677-80, this issue.]

PMID- 12209724
TI  - Cyclooxygenase-2 expression in endometrial carcinoma: correlation with
      clinicopathologic parameters and clinical outcome.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) is overexpressed in endometrial hyperplasia
      and carcinoma, but no data have been reported until now about the expression of
      COX-2 and its possible clinical significance in endometrial carcinoma. We
      investigated by immunohistochemistry the expression of COX-2 in a single
      institutional series of primary untreated endometrial carcinoma patients. The
      relationship between COX-2 expression and microsatellite instability (MI) status
      was also analyzed. METHODS: The study was conducted on 69 primary untreated
      endometrial carcinoma patients who were admitted to the Department of Obstetrics
      and Gynecology, Catholic University of Rome. Immunohistochemistry was performed
      by using rabbit polyclonal antiserum against human COX-2. Analysis of MI was
      performed for 47 patients with endometrial carcinomas. RESULTS: Twenty-seven
      patients (39.1%) were scored as COX-2 positive. COX-2 positivity was higher
      (60.8%) in endometrial carcinoma with cervical or extrauterine involvement than
      in tumors limited to the corpus (28.3%; P = 0.0174). COX-2 positivity increased
      from Grade 1 (13.6%) to Grade 2 (41.7%) to Grade 3 (60.9%) endometrial carcinoma
      (P = 0.0049). Interestingly, considering early International Federation of
      Gynecology and Obstetrics stage patients (n = 53), the percentage of COX-2
      positivity was higher in patients with deep myometrial invasion (66.7%) than in
      patients without or less than 50% myometrial invasion (15.6%) (P = 0.0003). No
      association between COX-2 and MI status was found. COX-2-positive patients showed
      a trend to a shorter disease-free survival than COX-2-negative patients (P =
      0.09). CONCLUSIONS: COX-2 is expressed in a high percentage of a large series of
      primary endometrial tumors and its expression may be associated closely with
      parameters of tumor aggressiveness The possible prognostic role of COX-2 in
      endometrial carcinoma deserves further study.

PMID- 12209725
TI  - Vascular endothelial growth factor and social support in patients with ovarian
      carcinoma.
AB  - BACKGROUND: The modulation of immunologic activities relevant to cancer by
      behavioral factors, such as stress, depression, and social support, is well
      documented. However, associations of behavioral factors with cytokines involved
      in tumor angiogenesis have not been studied. Vascular endothelial growth factor
      (VEGF) is a key cytokine that is capable of stimulating tumor angiogenesis, and
      it has been associated with poorer survival in patients with ovarian carcinoma.
      VEGF is modulated by a variety of behaviorally sensitive factors, including
      sympathetic activation. This study examined relationships of social support and
      depressive symptoms with VEGF levels in preoperative patients with ovarian
      carcinoma. METHODS: Twenty-four women with ovarian carcinoma and 5 women with
      benign pelvic masses were recruited at the presurgical clinic visit, received
      psychosocial surveys, including the Functional Assessment of Cancer Therapy
      (Quality of Life) survey and the Profile of Mood States, and a blood draw. Serum
      VEGF levels were assessed by enzyme-linked immunosorbent assay. Analyses
      controlled for disease stage. RESULTS: Women with ovarian carcinoma who reported
      higher levels of social well being had lower levels of VEGF (P = 0.005). Greater
      support from friends and neighbors (P = 0.005) and less distance from friends (P
      = 0.04) were facets of social well being that were associated with lower VEGF
      levels. Individuals who reported greater helplessness (P = 0.03) or worthlessness
      (P = 0.08) had higher VEGF levels, but depression as a whole (P > 0.50) was not
      related to VEGF levels. CONCLUSIONS: Higher levels of social well being were
      correlated with lower VEGF levels in presurgical patients with ovarian carcinoma.
      These findings suggest a possible mechanism by which poor social support may be
      associated with disease progression. Further study of these relations may
      demonstrate novel pathways relating biobehavioral factors to tumor growth and
      disease progression.

PMID- 12209726
TI  - Hepatocellular carcinoma in elderly patients: beneficial therapeutic efficacy
      using percutaneous ethanol injection therapy.
AB  - BACKGROUND: The age of patients with hepatocellular carcinoma (HCC) has been
      increasing worldwide. The objective of this study was to assess the efficacy and
      safety of percutaneous ethanol injection therapy (PEIT) in elderly patients with
      HCC. METHODS: The authors retrospectively analyzed 653 patients who were treated
      with PEIT between 1985 and 1997. One hundred thirty-seven patients were age > or
      = 70 years, 90 of 137 patients (66%) were male, and 106 of 137 patients (77%)
      were positive for hepatitis C virus antibodies. Both survival rates and
      standardized mortality ratios (SMRs) related to the causes of death were compared
      between patients age > or = 70 years and patients age < 70 years. RESULTS: With
      the exception of greater maximum tumor size in elderly patients age > or = 70
      years, the clinical features of tumors and underlying liver disease were similar
      to those of patients age < 70 years The survival rates after PEIT in patients age
      > or = 70 years were 83%, 52%, and 27% at 1 year, 3 years, and 5 years,
      respectively. These results were comparable to the rates for patients age < 70
      years (1 year, 90%; 3 years, 65%; and 5 years, 40%). In addition, there was no
      difference in mortality from extrahepatic disease between the two groups (9.8%
      for patients age > or = 70 years vs. 9.4% for patients age < 70 years; P >
      0.999). The SMR of patients age > or = 70 years who died of causes related to
      extrahepatic disease (SMR, 0.56; 95% confidence interval [95%CI], 0.18-1.30) was
      lower compared with the SMR of patients age < 70 years (SMR, 1.75; 95%CI, 1.07
      2.71). The SMR of patients age > or = 70 years who died of causes related to
      liver disease (SMR, 115; 95%CI, 84.1-153.0) was similar to that of patients age <
      70 years (SMR, 120; 95%CI, 103.0-138.0). CONCLUSIONS: These results provide
      support for the treatment of patients with HCC age > or = 70 years by tumor
      ablation using PEIT.

PMID- 12209727
TI  - Serum concentrations of human hepatocyte growth factor is a useful indicator for
      predicting the occurrence of hepatocellular carcinomas in C-viral chronic liver
      diseases.
AB  - BACKGROUND: Numerous reports have examined the relationship between hepatocyte
      growth factor (HGF) and either the facilitation or suppression of the occurrence
      of hepatocellular carcinoma (HCC). METHODS: In this study, we measured serum HGF
      concentrations of blood samples and conducted prospective studies to examine the
      long-term outcome of C-viral chronic hepatitis (CH) and cirrhosis in patients.
      The subjects examined in this study include 99 patients with C-viral CH,
      cirrhosis, and HCC. The serum HGF level was measured in blood samples within 48
      hours of collection using enzyme-linked immunosorbent assay kits. RESULTS: The
      serum concentrations of HGF were significantly higher in patients with HCC than
      in patients with CH or cirrhosis. The detection rate of HGF and its mean serum
      level were significantly higher in patients with a low platelet count than in
      patients with a high platelet count. All of the patients with serum HGF
      concentrations of more than 0.6 ng/mL had HCC, irrespective of the levels of
      alpha-fetoprotein, vitamin K absence, or antagonist-II in the blood. Serum HGF
      concentrations increased concomitantly with increases in areas occupied by HCC.
      The cumulative incidence of occurrence of HCC was significantly higher in
      patients with high HGF concentrations than in patients with low HGF
      concentrations. Multivariate analysis revealed that the elevation in serum HGF
      level is the most important risk factor for the occurrence of HCC. CONCLUSIONS:
      The serum level of HGF represents the degree of the carcinogenic state in the
      liver of patients with C-viral CH and cirrhosis. Therefore, the determination of
      serum HGF concentrations may be useful as a third tumor marker of HCC in
      detection as well as follow-up therapy.

PMID- 12209728
TI  - Contrast-enhanced dynamic computed tomography for the evaluation of tumor
      angiogenesis in patients with lung carcinoma.
AB  - BACKGROUND: The objective of this study was to investigate the role of contrast
      enhanced dynamic computed tomography (CT) in the evaluation of tumor angiogenesis
      in patients with lung carcinoma and to assess its importance in predicting tumor
      size and lymph node involvement. METHODS: Dynamic CT scans were evaluated
      retrospectively in 130 patients with primary lung carcinoma who did not have
      distant metastasis and who underwent surgical resection with mediastinal lymph
      node dissection. Histopathologic findings of vascular endothelial growth factor
      (VEGF) expression and microvessel density (MVD) were correlated with the maximum
      attenuation values of time-attenuation curves (MAV) on dynamic CT scans. RESULTS:
      The MAV in VEGF positive tumors was greater compared with the MAV in VEGF
      negative tumors (66.1 +/- 4.6 vs. 30.9 +/- 2.7, respectively; P < 0.0001). An
      association was found between the MAV in VEGF positive tumors and MVD
      (correlation coefficient = 0.650; P < 0.0001). No difference was found in tumor
      size with pathologic confirmation and the MAV, VEGF expression, or MVD. The MAV,
      VEGF expression, and MVD in lung tumors with lymph node involvement were greater
      compared with the same values in lung tumors without lymph node involvement.
      CONCLUSIONS: The MAV of dynamic CT may be a predictor of tumor angiogenesis in
      patients with lung carcinoma and lymph node involvement.

PMID- 12209729
TI  - Prognostic significance of grading and staging systems using MIB-1 score in adult
      patients with soft tissue sarcoma of the extremities and trunk.
AB  - BACKGROUND: The predictive value of histologic grading and staging systems for
      overall survival in different types of adult soft tissue sarcoma of the
      extremities and trunk is unclear. METHODS: Histologic slides from 193 patients
      with primary tumors were reviewed for diagnosis, and Ki-67 (MIB-1) immunostaining
      was performed for grading in all patients. Univariate and multivariate analyses
      were conducted to analyze the results from patients with soft tissue sarcomas as
      a group and among the six main histologic categories: malignant fibrous
      histiocytoma (n = 49 patients), liposarcoma (n = 48 patients), synovial sarcoma
      (n = 30 patients), spindle cell sarcoma (n = 24 patients), small round cell
      sarcoma (n = 15 patients), and others (n = 27 patients). The median follow-up was
      50 months. RESULTS: Univariate analysis of soft tissue sarcomas showed that tumor
      size and depth, histologic type, MIB-1 score, grades based on three criteria
      (tumor differentiation/histologic type, necrosis, and either mitosis or MIB-1
      score) and disease stage, as assessed by tumor size, depth, and grade, were
      associated with overall survival. Among these variables, grading and staging
      systems using the MIB-1 score had better predictive value compared with the MIB-1
      score and standard grading and staging models in the main histologic categories.
      Because survival curves for the different tumor grades and stages showed similar
      trends between the different histologic types, multivariate analysis was
      conducted adjusting for age, gender, disease site, surgical margin, tumor size
      and depth, grade, stage, and histologic type. Consequently, Grade 3 emerged as
      the most significant adverse prognostic factor. Additional adverse prognostic
      factors were Stage III, Grade 2, a histologic type of spindle cell sarcoma, and
      patient age > 50 years at the time of presentation. The histologic type
      liposarcoma was identified as a favorable prognostic factor. CONCLUSIONS: The
      current results indicate that grading and staging systems using the MIB-1 score
      are very strong prognostic factors in patients with the main histologic types of
      soft tissue sarcoma. Specific assessment of histologic type should be carried out
      before deciding on treatment strategies.

PMID- 12209730
TI  - Surgical management of soft tissue sarcomas of the hand and foot.
AB  - BACKGROUND: Soft tissue sarcomas of the hand and foot present unique management
      challenges. The purpose of the current study study was to determine oncologic
      outcome, particularly with respect to factors affecting local recurrence, distant
      recurrence, and disease-specific survival. METHODS: A retrospective study was
      performed on 115 patients with soft tissue sarcomas of the hand or foot who were
      evaluated, treated, and followed at the authors' institution between 1980 and
      1998. The medical records and radiographs were reviewed. Kaplan-Meier analysis
      was used to assess patient survival. RESULTS: Most patients (95%) were referred
      after previous surgery. The majority of tumors (75%) were T1 lesions (less than 5
      cm), and most tumors (81%) were high grade. Patients who were treated by
      definitive, wide re-excision (n = 43) had a 10 year local recurrence-free
      survival of 88%, which was significantly better than the corresponding rate of
      58% for patients who did not have re-excision (n = 40, P = 0.05). Radiation
      improved local control in patients who did not undergo re-excision (n = 17, P =
      0.02). However, radiation did not improve local control in patients who had
      definitive re-excision with negative margins (n = 13, P = 0.51). The disease
      specific survival at 5 and 10 years was 76% and 65%, respectively, for patients
      who presented with localized disease. Disease-specific patient survival was
      significantly worse for patients who had regional or distant metastasis. Radical
      amputation as initial surgical treatment did not decrease the likelihood of
      regional metastasis and did not improve disease-specific patient survival. The
      presence of distant metastasis at presentation was an independent predictor of
      local recurrence. CONCLUSION: Limb sparing treatment is possible in many patients
      with soft tissue sarcomas of the hand and foot. Re-excision to achieve
      microscopically negative surgical margins is an effective method of achieving a
      high rate of local control in appropriately selected patients who present after
      unplanned excision of the primary tumor. There does not appear to be a survival
      benefit to immediate radical amputation, which should be reserved for cases where
      surgical excision or re-excision with adequate margins cannot be performed
      without sacrifice of functionally significant neurovascular or osseous
      structures.

PMID- 12209731
TI  - Human osteosarcoma expresses specific ephrin profiles: implications for
      tumorigenicity and prognosis.
AB  - BACKGROUND: The molecular mechanisms underlying malignancy of osteosarcoma are
      unknown. It has been reported that eph receptor protein tyrosine kinases and
      their ligands, ephrins, are associated with increased tumorigenicity in patients
      with breast carcinoma and melanoma. The expression and role of eph/ephrins in
      human osteosarcoma has not yet been characterized. METHODS: Ephrin-A1, ephrin-A3,
      ephrin-A4, ephrin-A5, ephrin-B1, ephrin-B2, and ephrin-B3 mRNA expression was
      examined by reverse transcription polymerase chain reaction analysis in nine
      specimens of human osteosarcoma tissue and five human osteosarcoma cell lines.
      Ephrin-B1 protein expression was detected immunohistochemically in human
      osteosarcoma tissue. Clinicopathologic correlation was made between the
      osteosarcoma specimens and their ephrin expression profiles. RESULTS: Normal bone
      specimens, osteosarcoma tissue specimens, and osteosarcoma cell lines expressed a
      distinct mRNA profile of ephrin-A1, ephrin-A4, and ephrin-B2. A second mRNA
      profile that included ephrin-A3, ephrin-A5, and ephrin-B1 was expressed by a
      subset of tumors. The expression of ephrin-B1 was correlated with a poorer
      clinical prognosis. Ephrin-B1 protein was expressed by osteosarcoma cells and
      blood vessels. CONCLUSIONS: The results of this study suggest that ephrin-B1
      expressed by osteosarcoma may be a poor prognostic marker through increased
      tumorigenicity.

PMID- 12209732
TI  - Modeling the impact of the decline in distant stage disease on prostate carcinoma
      mortality rates.
AB  - BACKGROUND: The incidence of distant stage prostate carcinoma was relatively flat
      until 1991 and then started declining rapidly. This decline probably was caused
      by the shift to earlier stage disease associated with the rapid dissemination of
      prostate specific antigen (PSA) screening. Prostate carcinoma mortality rates
      started falling at approximately the same time. In this article, the authors
      model the potential impact of this stage shift on prostate carcinoma mortality
      rates given various assumptions concerning the survival of patients with screen
      detected local-regional disease. METHODS: The authors used the CAN*TROL 2
      computer model to shift each deficit in the number of patients with distant stage
      disease to local-regional stage disease and modeled the implications on mortality
      using a set of base, optimistic, and pessimistic survival assumptions. A base
      survival assumes that a patient with screen-detected local-regional disease of a
      certain histologic grade has the same prognosis as a patient with clinically
      detected local-regional disease of same grade (i.e., an assumption of no length
      bias for patients with screen-detected disease), whereas the optimistic and
      pessimistic scenarios assume that survival is better or worse, respectively, than
      the base survival (i.e., complete cure for patients with favorable grade for the
      optimistic scenario and no improvements in survival for patients with unfavorable
      grade for the pessimistic scenario). RESULTS: Model results were compared with
      observed mortality trends. Rising age-adjusted mortality rates peaked in 1991 for
      white males and in 1993 for black males and then fell 21% and 13% for white males
      and black males, respectively, from 1990 through 1999. Under the modeled stage
      shift intervention, mortality rates would fall 18%, 8%, and 19% for both white
      males and black males under the base, pessimistic, and optimistic assumptions,
      respectively. CONCLUSIONS: It is impossible to know what the mortality trends
      would have been in the absence of the introduction of PSA screening. However,
      under the base assumption, it appears that the decline in distant stage disease
      can have a fairly sizable and rapid impact on population mortality. The
      optimistic scenario is not much improved over the base scenario, which is
      indicative of the facts that the survival of patients diagnosed with clinical
      local-regional prostate carcinoma is quite good and that further survival
      improvements can have only a marginal impact. Under the pessimistic scenario, it
      appears that something else must be responsible for much of the decline in
      mortality. Screening trial results from the United States and Europe may verify
      and isolate the size of any mortality benefit associated with PSA screening.
      Trial results eventually can be put back into these population models to help
      quantify the impact of screening, treatment, and other factors on population
      trends.

PMID- 12209733
TI  - Severe periorbital edema secondary to STI571 (Gleevec).
AB  - STI571 (imatinib mesylate; Gleevec) is a selective inhibitor of the bcr-abl, c
      kit, and platelet-derived growth factor receptor tyrosine kinases. Mild
      periorbital edema has been noted as a common side effect in Phase I and II trials
      of this drug for the treatment of patients with chronic myelogenous leukemia and
      gastrointestinal stromal tumors. The authors report the case of male patient age
      63 years who developed severe periorbital edema after treatment with STI571 for
      chronic myelogenous leukemia. His edema was severe enough to cause visual
      obstruction due to lower eyelid festoons that ultimately required surgical
      debulking. Histopathologic analysis of specimens of the excised upper and lower
      eyelid tissue revealed dermal dendrocytes that expressed the platelet-derived
      growth factor receptor and c-kit tyrosine kinases, suggesting a possible role for
      dermal dendrocytes in the development of this toxic effect.

PMID- 12209734
TI  - Relationship between changes in hemoglobin level and quality of life during
      chemotherapy in anemic cancer patients receiving epoetin alfa therapy.
AB  - BACKGROUND: Hemoglobin increases have been associated with quality of life (QOL)
      improvements in anemic cancer patients treated with epoetin alfa, but
      intervention generally has been reserved for symptomatic anemia or hemoglobin <
      10 g/dL. Relationships among hemoglobin, functional status, and patient reported
      QOL have not been well characterized. METHODS: Data from two open-label,
      community-based trials of epoetin alfa therapy that enrolled 4382 anemic cancer
      patients undergoing chemotherapy were used to evaluate the relationship between
      hemoglobin changes and QOL changes. The authors measured QOL using the Linear
      Analog Scale Assessment (LASA) and the more detailed, disease-specific Functional
      Assessment of Cancer Therapy-Anemia (FACT-An) instrument. Analyses were performed
      to determine the incremental change in QOL associated with hemoglobin increases
      (1 g/dL increments). RESULTS: Cross-sectional analyses showed a nonlinear
      relationship and significant positive correlation between high hemoglobin levels
      and high LASA and FACT-An scores (r = 0.25 and 0.29, respectively, P < 0.01).
      Patients with hemoglobin increases of > or = 2 g/dL reported statistically
      significant improvements in five FACT-An items selected a priori specifically to
      reflect functional capacity. An incremental analysis used regression methods to
      identify the longitudinal relationship between incremental changes in hemoglobin
      and QOL scores. This relationship was found to be nonlinear, with the maximum QOL
      gain occurring at a hemoglobin level of 12 g/dL (range, 11-13 g/dL). Patients
      with low baseline QOL scores and longer time periods between baseline and final
      QOL assessments experienced significantly (P < 0.05) greater increases in overall
      QOL. Progressive disease at baseline, change in disease status from baseline to
      end of study, and increase in self-reported pain or nausea all had significant (P
      < 0.05) negative effects on QOL scores. CONCLUSIONS: A direct relationship exists
      between hemoglobin increases during epoetin alfa therapy and corresponding QOL
      improvements in cancer patients receiving chemotherapy across the clinically
      relevant hemoglobin range of 8-14 g/dL. These data suggest that the maximal
      incremental gain in QOL occurs when hemoglobin is in the range of 11-13 g/dL.

PMID- 12209735
TI  - Beta 1-integrin protects hepatoma cells from chemotherapy induced apoptosis via a
      mitogen-activated protein kinase dependent pathway.
AB  - BACKGROUND: beta 1-integrin modulates cellular phenotype by mediating signals
      from the extracellular matrix (ECM). Although overexpression of integrin
      molecules in hepatocellular carcinoma (HCC) has been reported, the role of
      overexpressed beta 1-integrin in the disease process of HCC is not fully
      understood. The authors investigated the effects of beta 1-integrin on apoptosis
      in hepatoma cells. METHODS: Human hepatoma cell lines HepG2, Huh7, and HLE were
      stably transfected with full-length beta 1-integrin. Cells underwent apoptosis
      induced by chemotherapeutic reagents, including cis-platinum (II)-diammine
      dichloride, etoposide, and docetaxel. Cell survival and intracellular signaling
      pathways dependent on beta 1-integrin-mediated apoptosis effects were analyzed by
      treating cells with PD98059 (ERK inhibitor), SB203580 (p38MAP kinase inhibitor),
      wortmannin (phosphatidyl inositol-3-kinase inhibitor), and herbimycin A (tyrosine
      kinase inhibitor). RESULTS: All three hepatoma cell lines overexpressing beta 1
      integrin were protected from apoptosis induced by chemotherapeutic reagents,
      whereas parental or mock transfected cells were not. Treatment with PD98059 or
      SB203580 abolished the protective effect on apoptosis in cells overexpressing
      beta 1-integrin. Neither herbimycin nor wortmannin blocked the protective effects
      of beta 1-integrin overexpression. CONCLUSIONS: These data suggest that
      overexpression of beta 1-integrin confers resistance to apoptosis in hepatoma
      cells via a MAP kinase dependent pathway. beta1-integrin mediated signaling from
      the ECM in HCC cells may contribute to chemotherapy resistance.

PMID- 12209736
TI  - Effect of service screening mammography on population mortality from breast
      carcinoma.

PMID- 12209737
TI  - The impact of organized mammography service screening on breast carcinoma
      mortality in seven Swedish counties.
AB  - BACKGROUND: The evaluation of organized mammographic service screening programs
      is a major challenge in public health. In particular, there is a need to evaluate
      the effect of the screening program on the mortality of breast carcinoma,
      uncontaminated in the screening epoch by mortality from 1) cases diagnosed in the
      prescreening period and 2) cases diagnosed among unscreened women (i.e.,
      nonattenders) after the initiation of organized screening. METHODS: In the
      current study, the authors ascertained breast carcinoma deaths in the
      prescreening and screening epochs in 7 Swedish counties from tumors diagnosed in
      these epochs and in the age group 40-69 years in 6 counties and 50-69 years in 1
      county. Data regarding deaths were obtained from the Uppsala Regional Oncologic
      Center in conjunction with the National Cause of Death Register. The total number
      of women in the eligible age range living in each county was obtained from the
      annual population data of Statistics Sweden. Detailed screening data were
      provided by the screening centers in the seven counties, including the number of
      invited, the number attended, and whether each individual breast carcinoma case
      was exposed (screen-detected and interval cases combined) or unexposed (not
      invited or nonattenders) to mammographic screening. There were 2044 breast
      carcinoma deaths from 14,092 incident tumors diagnosed in the prescreening and
      screening epochs, and the total number of person-years was 7.5 million. Data were
      analyzed using Poisson regression with corrections for self-selection bias and
      lead-time bias when appropriate. RESULTS: The mortality reduction for breast
      carcinoma in all 7 counties combined for women actually exposed to screening
      compared with the prescreening period was 44% (relative risk [RR] = 0.56; 95%
      confidence interval [95% CI], 0.50-0.62). When all incident tumors were
      considered, both those exposed and those unexposed to screening combined,
      counties with > 10 years of screening were found to demonstrate a significant 32%
      mortality reduction (RR = 0.68; 95% CI, 0.60-0.77) and counties with < or = 10
      years of screening showed a significant 18% reduction in breast carcinoma
      mortality (RR = 0.82; 95% CI, 0.72-0.94) for the screening epoch compared with
      the prescreening epoch. Within the screening epoch, after adjustment for self
      selection bias, a 39% mortality reduction (RR = 0.61; 95%CI, 0.55-0.68) was
      observed in association with invitation to screening. CONCLUSIONS: Organized
      service screening in 7 Swedish counties, covering approximately 33% of the
      population of Sweden, resulted in a 40-45% reduction in breast carcinoma
      mortality among women actually screened. The policy of offering screening is
      associated with a mortality reduction in breast carcinoma of 30% in the invited
      population, exposed and unexposed combined. The results of the current study
      indicate that the majority of the breast carcinoma mortality reduction is indeed
      due to the screening.

PMID- 12209738
TI  - Detection method and breast carcinoma histology.
AB  - BACKGROUND: The association between method of detection and breast carcinoma
      histopathology has not been assessed adequately in a population-based setting.
      METHODS: Among women who were included in a population-based, case-control study
      of breast cancer, patients who were newly diagnosed with invasive breast
      carcinoma were identified from Wisconsin's statewide tumor registry. Only women
      age > or = 50 years were analyzed, because screening by mammography was not
      recommended before age 50 years at the time of the study. The breast tumors among
      these women (n = 2341 tumors) included the following histopathologies: lobular
      carcinoma (n = 206 tumors); ductal carcinoma, not otherwise specified (n = 1920
      tumors); papillary carcinoma (n = 15 tumors); medullary carcinoma (n = 36
      tumors); mucinous adenocarcinoma (n = 56 tumors); tubular adenocarcinoma (n = 41
      tumors); invasive comedocarcinoma (n = 24 tumors); scirrhous adenocarcinoma (n =
      15 tumors); and mixed ductal/lobular carcinoma (n = 28 tumors). RESULTS: Overall,
      women reported that 41% of tumors were detected by mammography, 48% of tumors
      were self detected, and 11% of tumors were detected by clinical breast
      examination (CBE). Detection by mammography was significantly more likely for
      women who had tubular carcinoma (83%; P < 0.001) and invasive comedocarcinoma
      (67%; P = 0.23) compared with women who had ductal carcinoma (40%). Mammography
      was significantly less likely to detect medullary carcinoma (17%) than ductal
      carcinoma (40%; P = 0.01). Lobular carcinoma was the only histopathology that,
      compared with ductal carcinoma, was detected significantly more often by CBE than
      by self detection. Mammography detected lobular carcinoma (42%) as frequently as
      ductal carcinoma (40%). However, the use of postmenopausal hormones may have
      modified these detection patterns: Among current users, mammography discovered a
      greater percentage of ductal carcinomas (51%) and fewer lobular carcinomas (36%)
      than nonusers. CONCLUSIONS: Among women age > or = 50 years, breast cancer
      detection by mammography, self detection, and CBE varied according to tumor
      histopathology.

PMID- 12209740
TI  - Follicular thyroid carcinoma: prognostic factors and the role of radioiodine.
AB  - BACKGROUND: The objective of this study was to investigate the patterns of
      recurrence, various prognostic factors, and the role of radioiodine in the
      treatment of patients with follicular thyroid carcinoma (FTC). METHODS: The
      clinical outcomes of 215 patients with FTC who were treated at a single
      institution were analyzed retrospectively. The mean follow-up was 10.8 years.
      RESULTS: The actuarial rates of cause specific survival (CSS), locoregional (LR)
      control, and freedom from distant metastasis (DM) at 10 years were 81%, 83%, and
      72.3%, respectively. The independent prognostic factors for survival were
      metastasis at presentation (relative risk [RR], 47.7), radioiodine (RAI)
      treatment (RR, 0.25), extrathyroidal extension (RR, 3.8), and the postoperative
      absence of macroscopic disease in the neck region (RR, 0.06). In patients who
      were treated with RAI, both the LR failure rate (RR, 0.24) and the mortality rate
      (RR, 0.25) were reduced to about 25%. Subgroup analysis revealed that RAI
      improved the survival of patients with DM at presentation (RR, 0.17) and improved
      the LR control rate in patients who had no DM at presentation (RR, 0.13). For
      patients who underwent total thyroidectomy with negative resection margins, RAI
      significantly reduced the rate of LR recurrence (RR, 0.05). Patients with the
      minimally invasive type of FTC had a good prognosis. The 10-year rates for CSS,
      LR control, and freedom from DM were 97.6%, 100%, and 90.6%, respectively. The
      prognosis of patients with frankly invasive FTC was much poorer. The 10-year
      rates for CSS, LR control, and freedom from DM were 66.7%, 100%, and 45%,
      respectively. CONCLUSIONS: RAI is an effective treatment for patients with FTC.
      It was associated with improved survival rates and fewer recurrences.

PMID- 12209739
TI  - Optimal use of sentinel lymph node biopsy versus axillary lymph node dissection
      in patients with breast carcinoma: a decision analysis.
AB  - BACKGROUND: There are no data available from randomized controlled trials that
      compare the efficacy of sentinel lymph node (SLN) biopsy with Level I/II axillary
      lymph node dissection (ALND) in patients with breast carcinoma. We performed a
      formal decision analysis to determine whether SLN biopsy is appropriate, compared
      with ALND, for patients with T1, T2, and T3 tumors and to quantify the relative
      value of these two procedures in the management of patients with breast
      carcinoma. METHODS: All clinically relevant outcomes were modeled for both SLN
      biopsy and ALND. The probabilities of complications and outcomes were derived
      using data from the University of Louisville Breast Cancer Sentinel Lymph Node
      Study and from extensive review of previous studies. Utilities were assigned by
      the authors, incorporating values from the literature whenever possible. RESULTS:
      The expected utility of SLN biopsy was higher than the expected utility for ALND
      for T1 and T2 tumors that were 4.0 cm or smaller. There was no clear preference
      for either procedure with tumors that were larger than 4.0 cm. The T1 and T2
      results were robust to sensitivity analysis. CONCLUSIONS: The results of this
      decision analysis suggest that SLN biopsy is preferred over ALND for patients
      with breast tumors that are 4.0 cm or smaller. Patients should be aware of the
      potential for false-negative results in SLN biopsy, but this risk is outweighed
      by the decreased morbidity associated with the procedure itself.

PMID- 12209741
TI  - Study of p53 immunostaining in the gastric epithelium of cagA-positive and cagA
      negative Helicobacter pylori gastritis.
AB  - BACKGROUND: p53 mutations are an early event in the multistep progression of
      gastric carcinoma. These mutations are often present in dysplastic and intestinal
      metaplastic gastric epithelium. However, the presence of immunohistochemically
      detectable p53 protein and p53 mutations in nondysplastic/nonmetaplastic gastric
      mucosa is more controversial. Recent reports have suggested that
      immunohistochemically detectable p53 protein may be present in the gastric
      epithelium of Helicobacter pylori gastritis. Furthermore, because cagA-positive
      H. pylori is associated with greater mucosal injury but decreased apoptosis, it
      would be interesting to determine if this phenotype is associated with greater
      immunostaining of p53, as the wild-type p53 gene helps to initiate apoptosis.
      METHODS: One hundred thirty-five patients with H. pylori-associated gastritis
      were immunohistochemically stained for p53 and quantified for the extent and
      intensity of the staining using a semiquantitative method (0, nil staining; 6,
      extensive and strong staining). The cagA status of the organism was determined by
      Western blot. RESULTS: Thirty-one patients (23%) showed strong p53 staining (> or
      = 4 of 6) in inflamed but otherwise normal gastric epithelium. In the 123 cagA
      positive H. pylori gastritis patients, the average p53 staining score was 2.5 of
      6. This is significantly higher than the corresponding score of 1.7 of 6 observed
      in the 12 patients with cagA-negative H. pylori gastritis (P = 0.04).
      CONCLUSIONS: Our results indicate that p53 protein is immunohistochemically
      detectable even before gastric metaplastic/dysplastic change occurs. The results
      also suggest that cagA-positive H. pylori might be associated with greater p53
      immunohistochemical staining. This would indicate that p53 immunohistochemical
      staining does not reliably differentiate between gastric dysplasia and reactive
      inflammatory atypia. If the p53 protein detected is a consequence of mutation,
      this would help to explain why cagA-positive H. pylori gastritis is associated
      with decreased apoptosis.

PMID- 12209742
TI  - Plasma osteopontin: associations with survival and metastasis to bone in men with
      hormone-refractory prostate carcinoma.
AB  - BACKGROUND: Osteopontin (OPN) is a secreted glycoprotein that is detectable in
      human body fluids. Its increased expression has been found in many malignancies,
      and a stimulatory effect on human prostate carcinoma cells in vitro has been
      demonstrated. Plasma OPN levels have been associated with tumor burden and
      survival in patients with metastatic breast carcinoma. The authors explored these
      associations in men with hormone-refractory prostate carcinoma (HRPC). METHODS:
      Plasma samples from 100 men with HRPC were collected. OPN was measured using an
      antigen-capture enzyme-linked immunosorbent assay technique. Multivariable
      analyses were performed to identify predictors of OPN and survival. RESULTS: At
      the time of OPN sampling, the median patient age was 73 years (range, 50-86
      years), and 92% of patients had metastases. The median plasma OPN level was 198.5
      ng/mL (range, 15.0-2363.0 ng/mL), the median prostate specific antigen level was
      67.8 microg/L (range, 0.1-7550.0 microg/L), and the median survival was 13.7
      months. OPN plasma levels were higher in patients with versus patients without
      bone metastases (P = 0.024). Multivariable modeling demonstrated an independent
      association of the OPN level with alkaline phosphatase, hemoglobin, and
      creatinine levels. The log-transformed OPN level (hazard ratio [HR], 2.38; P <
      0.0001), performance status (HR, 2.43; P = 0.007), and a history of prior
      radiotherapy for localized prostate carcinoma (HR, 0.48; P = 0.0229) were
      independent predictors of survival in a Cox multivariate model. CONCLUSIONS: In
      this study, in men with established HRPC, the plasma OPN level was associated
      with the presence of metastases to bone and with other measures of tumor burden,
      and it was correlated independently and negatively with survival.

PMID- 12209743
TI  - The relevance of prostatectomy findings for brachytherapy selection in patients
      with localized prostate carcinoma.
AB  - BACKGROUND: The efficacy of brachytherapy for patients with localized prostate
      carcinoma depends on adequate radiotherapeutic coverage of the primary tumor and
      its subclinical extraprostatic extensions. Predictive models based on pretherapy
      factors may be useful to estimate the likelihood for clinically relevant
      extraprostatic disease and may be incorporated into selection criteria for this
      procedure. METHODS: Multivariate logistic regression model building was performed
      using pretherapy factors in 2905 surgically staged patients with localized
      prostate carcinoma to estimate the probability of seminal vesicle and/or lymph
      node involvement. Bootstrap methods were employed to assess the stability of the
      final model parameters and to determine the sensitivity and specificity of the
      final model. RESULTS: Clinical tumor classification, biopsy Gleason score
      groupings, and serum prostate specific antigen (PSA) levels were associated with
      seminal vesicle and/or pelvic lymph node involvement. These factors were
      incorporated into a multivariate model that predicted for these adverse
      histopathologic features. Allowing for up to a 10% likelihood for seminal vesicle
      and/or pelvic lymph node involvement, patients with tumors classified as T1c-T2a,
      Gleason scores of 2-6, and PSA < or = 16 ng/mL; or with tumors classified as T1c
      T2a, Gleason scores of 7-10, and PSA < or = 4 ng/mL; or with tumors classified as
      T2b-T2c, Gleason scores of 2-6, and PSA < or = 6 ng/mL would be potential
      candidates for brachytherapy alone. CONCLUSIONS: The predictive model presented
      may provide criteria whereby an adequately performed prostate brachytherapy
      procedure is expected to encompass the intraprostatic and adjacent extraprostatic
      disease. Prostate brachytherapy alone may be considered in these circumstances,
      whereas the addition of external beam radiotherapy may be reserved for patients
      with disease that is apt to extend beyond the brachytherapy target volume.

PMID- 12209744
TI  - Late recurrence in 1263 men with testicular germ cell tumors. Multivariate
      analysis of risk factors and implications for management.
AB  - BACKGROUND: Testicular germ cell tumors are highly curable. However, 10-30% of
      patients have recurrence after initial treatment. The time-course of recurrence
      has implications for the duration of follow-up. This study was undertaken to
      assess the risk and time-course of recurrence and to identify patients at higher
      risk of late recurrence. METHODS: The records of 1263 patients with primary
      testicular germ cell tumors presenting to the Royal Marsden Hospital between
      December 1979 and December 1993 were reviewed. In all, 255 episodes of recurrence
      were documented (including 44 patients with multiple recurrences) and used to
      calculate recurrence-free survivals. RESULTS: Fifty-three patients (15 seminomas;
      38 nonseminomatous germ cell tumors [NSGCT]) had recurrence more than 2 years
      after initial presentation. A multivariate analysis of risk of recurrence after 2
      years identified positive markers at presentation and the presence of
      differentiated teratomas in postchemotherapy surgical specimens as significant
      predictors. Very late recurrence (> 5 years) occurred mainly in patients with
      metastatic NSGCT (12 of 14 patients) with a 1% annual risk of recurrence between
      5 and 10 years. Very late recurrence was also seen in one case of metastatic
      seminoma and one case of Stage I NSGCT managed by surveillance. Most late
      recurrences (n = 9) were detected at routine annual follow-up visits but five had
      recurrences with symptoms leading to an unscheduled clinic visit. CONCLUSION:
      Late recurrences are rare in patients with testicular germ cell tumors and follow
      up to detect recurrence may not be needed after 5 years, except in those
      presenting with metastatic NSGCTs.

PMID- 12209745
TI  - Overexpression of cyclooxygenase-2 is associated with a poor prognosis in
      patients with squamous cell carcinoma of the uterine cervix treated with
      radiation and concurrent chemotherapy.
AB  - BACKGROUND: The objective of this study was to determine whether cyclooxygenase-2
      (COX-2) overexpression was an indicator of prognosis in patients with
      International Federation of Gynecology and Obstetrics (FIGO) Stage IIB uterine
      cervical carcinoma who underwent radiation and concurrent chemotherapy. METHODS:
      Seventy-five patients with FIGO Stage IIB squamous cell carcinoma (SCC) of the
      uterine cervix who were treated with radiotherapy and concurrent chemotherapy
      between 1991 and 1996 were divided into two groups according to their COX-2 level
      in an immunohistochemical study: the COX-2 negative group (n = 54 patients) and
      the COX-2 positive group (n = 21 patients). The clinicopathologic features,
      patterns of treatment failure, and survival data for patients in the COX-2
      positive group were compared with data from the patients in the COX-2 negative
      group. Univariate and multivariate analyses were performed to determine the
      prognostic factors that influenced patient survival. RESULTS: In the
      immunohistochemical study, COX-2 overexpression was observed in approximately 30%
      of patients with FIGO Stage IIB SCC of the uterine cervix. With delayed
      regression to the initial treatment, the treatment failure rate of patients in
      the COX-2 positive group was much higher compared with the treatment failure rate
      of patients in the COX-2 negative group. The higher incidence of central failure
      and lymph node failure for patients in the COX-2 positive group was statistically
      significant (48% for the COX-2 positive group vs. 13% for the COX-2 negative
      group). However, there was no difference in the incidence of hematogenous
      metastases between the two groups (5% for the COX-2 positive group vs. 7% for the
      COX-2 negative group). In addition, increased COX-2 expression in tumor cells
      also was correlated with a shorter interval to tumor recurrence (median interval
      to recurrence, 9 months in the COX-2 positive group vs. 26 months in the COX-2
      negative group). Compared with patients in the COX-2 negative group, patients in
      the COX-2 positive group had lower overall actuarial and disease free survival
      rates (overall 5-year actuarial survival rates: 56% for the COX-2 positive group
      vs. 94% for the COX-2 negative group; P = 0.003). Univariate and multivariate
      analyses showed that COX-2 overexpression was an independent prognostic factor
      that surpassed other well-known clinicopathologic parameters. CONCLUSIONS: COX-2
      overexpression can be used as a potent molecular risk factor in patients with
      FIGO Stage IIB SCC of the uterine cervix who are treated with radiotherapy and
      concurrent chemotherapy.

PMID- 12209746
TI  - Changes in presentation and survival of head and neck carcinomas in Northeastern
      Italy, 1975-1998.
AB  - BACKGROUND: During the last 20 years, survival rates of head and neck carcinoma
      patients in the United States and Europe have plateaued. To determine the factors
      that can reduce mortality rates, we examined changes in clinical presentation and
      survival rates across 24 years of treatment of head and neck carcinoma patients.
      METHODS: A retrospective study of patients with head and neck carcinoma was
      conducted from January 1, 1975, to December 31, 1998. We identified 2143 eligible
      patients with squamous cell carcinoma of the oral cavity, oropharynx,
      hypopharynx, and larynx. Changes in gender, clinical stage, and therapy were
      evaluated separately for each site of cancer across five consecutive periods.
      Probability of dying and overall survival rates were estimated. Odds ratios (ORs)
      and hazard ratios were calculated. RESULTS: An increase in T1 versus T2 or higher
      stage carcinoma was more probable for the oral cavity and larynx (OR = 4.1 and
      3.0, respectively) in the last versus the earliest period. An increase in radical
      treatments was more probable for carcinomas of the oral cavity, oropharynx,
      hypopharynx, and larynx (10.2, 34.8, 12.5, and 2.1-fold, respectively) in the
      last versus the earliest period. A decreasing trend of probability of dying from
      the first head and neck carcinoma during the 1970s versus the 1990s was found.
      The overall survival rates at 5 years was 32% in 1975-1978 versus 51% in 1989
      1993. CONCLUSIONS: In contrast with survival rates in the United States and
      Europe, our findings show a significant increase in overall survival rates during
      the last 20 years. This increase is attributable to changes in diagnostic
      therapeutic approaches and to early consultation with a physician for symptoms
      arising in the head and neck region.

PMID- 12209747
TI  - Weight loss predicts mortality after recurrent oral cavity and oropharyngeal
      carcinomas.
AB  - BACKGROUND: The prognosis of patients with recurrent tumors of the head and neck
      generally is considered poor. Better prediction of outcomes can help physicians
      counsel patients about the merits of additional treatment. The TNM system, which
      was created for patients with primary tumors, may not provide optimal
      information. Anatomic staging systems traditionally have ignored symptom-based
      variables, such as weight loss, despite their known prognostic value. The
      objectives of this study were 1) to measure the prognostic impact of weight loss,
      2) to evaluate the prognostic value of the TNM staging system, and 3) to create a
      practical staging system capable of predicting survival after patients develop
      recurrent tumors of the oral cavity and oropharynx. METHODS: A retrospective
      chart review was used to identify an inception cohort of patients seeking
      treatment for recurrent, persistent, and second primary tumors of the oral cavity
      and oropharynx at the University of Washington. The primary outcome variable was
      1-year survival. RESULTS: The 1-year survival rate for the cohort (n = 97
      patients) was 38%, with a median survival of 0.7 years. Multivariate analysis
      (Cox regression) identified weight loss, previous radiation to the head and neck,
      and TNM stage of the recurrent tumor as factors that had a substantial impact on
      mortality. A second multivariate technique called conjunctive consolidation was
      used to determine the relative quantitative impact of each variable on survival
      and to develop a clinical staging system. Weight loss and previous radiation had
      the greatest influence, and the use of just these two variables resulted in a
      three-tiered staging system with 1-year survival rates of 62% (16 of 26
      patients), 44% (18 of 41 patients), and 10% (3 of 30 patients). In contrast, the
      TNM staging system produced survival rates of 60% (patients with Stage I
      disease), 67% (patients with Stage II disease), 32% (patients with Stage III
      disease), and 32% (patients with Stage IV disease). CONCLUSIONS: The authors
      found substantial variation in survival after patients developed recurrent tumors
      of the oral cavity and oropharynx. Two readily available clinical variables-
      weight loss and previous radiation--were combined to create a clinically
      practical staging scheme with more prognostic power than the TNM staging system.
      Until molecular markers can reliably used be to predict outcomes, greater
      attention needs to be given to the utility of simple, inexpensive, and
      surprisingly powerful clinical variables.

PMID- 12209748
TI  - BPDE-induced lymphocytic 3p21.3 aberrations may predict head and neck carcinoma
      risk.
AB  - BACKGROUND: Tobacco exposure is an established risk factor for head and neck
      squamous cell carcinoma (HNSCC). Benzo[alpha]pyrene diol expoxide (BPDE), a main
      metabolic product of the tobacco smoke constituent benzo[alpha]pyrene, induces
      chromosomal aberrations at specific loci. Chromosomal aberrations in peripheral
      blood lymphocytes (PBLs) induced by BPDE may reflect individuals' genetic
      susceptibility to tobacco carcinogens. METHODS: This study was designed to detect
      BPDE-induced aberrations in PBLs at locus 3p21.3 in cultured lymphocytic cells.
      Our hypothesis is that the presence of BPDE-induced 3p21.3 aberrations is a
      biomarker of an individual's genetic susceptibility and that individuals with
      these aberrations are at an increased risk for HNSCC. PBL cultures from 52 cases
      and 54 controls were treated with 2 microM BPDE for 24 hours before the 3p21.3
      aberrations were assessed by fluorescence in situ hybridization. One thousand
      lymphocyte interphases were scored for each sample. RESULTS: We found that BPDE
      induced chromosome 3p21.3 aberrations occurred more frequently in cases (mean:
      31.4 per 1000 cells) than in controls (mean: 22.1 per 1000 cells; P < 0.001).
      However, when 6q27 was selected as a control locus, no such difference was
      observed (P = 0.545). When the 75th percentile value of induced aberrations in
      the controls was used as a cutoff point to classify 3p21.3 BPDE-induced
      sensitivity, 30 of the 52 cases (57.69%) and only 14 of the 54 controls (25.93%)
      were sensitive to BPDE exposure. This approach resulted in an odds ratio of 4.8
      (95% confidence interval: 1.87-12.28) for HNSCC risk associated with BPDE-induced
      3p21.3 aberrations. There was also a dose-response relationship between the
      number of BPDE-induced aberrations at 3p21.3 and risk for HNSCC. CONCLUSIONS: The
      results from this study demonstrated that 3p21.3 may be a specific molecular
      target of tobacco carcinogens and that BPDE sensitivity at this locus may reflect
      an individual's genetic susceptibility to HNSCC.

PMID- 12209749
TI  - Phase II trial of interferon-alpha-2a plus psolaren with ultraviolet light A in
      patients with cutaneous T-cell lymphoma.
AB  - PURPOSE: To evaluate the efficacy and side effects of psolaren with ultraviolet
      light A (PUVA) and interferon-alpha-2a (IFN-alpha-2a) in patients with mycosis
      fungoides (MF) and Sezary syndrome (SS). PATIENTS AND METHODS: From May 1993 to
      January 1999, 63 symptomatic patients with all stages of MF and SS were treated
      in a prospective Phase II trial with systemic escalating doses of IFN-alpha-2a
      combined with PUVA for 1 year, followed by indefinite PUVA maintenance in
      complete responding patients. RESULTS: Sixty-three patients were enrolled (Stage
      IA, n = 6; IB, n = 37; IIA, n = 3; IIB, n = 3; III, n = 12; IVA, n = 2). Ten
      patients had received previous therapy. The median follow-up duration for the
      entire cohort is 37 months. Of 63 patients, 51 achieved a complete response (CR;
      74.6%) or partial response (PR; 6%) to therapy. The median response duration is
      32 months. The 5-year overall survival rate is 91% and the 5-year disease-free
      survival rate is 75%. No life-threatening side effects were observed. Five
      patients stopped IFN-alpha-2a therapy due to toxicity. Eighty-four percent of the
      patients received more than 75% of the planned dose (12 million units three times
      a week). CONCLUSIONS: This combination of IFN-alpha-2a and phototherapy is an
      effective and safe therapy for patients with symptomatic MF.

PMID- 12209750
TI  - Prophylactic intrathecal methotrexate and hydrocortisone reduces central nervous
      system recurrence and improves survival in aggressive non-hodgkin lymphoma.
AB  - BACKGROUND: Central nervous system (CNS) recurrence is almost invariably fatal in
      patients with aggressive non-Hodgkin lymphoma (NHL). Although some protocols are
      intended to prevent CNS disease, the value of CNS prophylaxis in patients with
      aggressive NHL remains to be determined. METHODS: We retrospectively analyzed a
      cohort of 68 adults with NHL who had been treated uniformly with systemic
      chemotherapy and had attained complete remission (CR) of disease. Patients ranged
      in age from 15 to 77 years (median, 56 years). Median follow-up after CR was 40
      months. After CR was attained, 29 patients (Group A) received CNS prophylaxis
      consisting of four doses of intrathecal methotrexate 10 mg/m(2) and
      hydrocortisone 15 mg/m(2) as soon as they could tolerate it. The other 39
      patients (Group B) did not receive CNS prophylaxis. RESULTS: Although bulky mass
      (45% vs. 21%, P = 0.03) was more frequent in Group A than in Group B, none of the
      patients in Group A experienced CNS recurrence (0%), whereas CNS recurrence
      occurred in six patients in Group B (15%). This difference was significant (P =
      0.03). Multivariate logistic regression analysis for CNS recurrence identified no
      CNS prophylaxis (P = 0.01) and bone marrow involvement (P = 0.02) as independent
      predictors. Among patients without CNS disease, systemic recurrence occurred in 5
      patients in Group A and in 11 patients in Group B (P = 0.12). The 5-year overall
      survival rate from CR was 80% in Group A and 58% in Group B (P = 0.05). The 5
      year recurrence-free survival rate from CR was 85% in Group A and 51% in Group B
      (P = 0.01). CONCLUSIONS: Prophylactic intrathecal methotrexate and hydrocortisone
      injection reduces the incidence of CNS recurrence following CR in patients with
      aggressive NHL and improves the chance of long-term survival.

PMID- 12209751
TI  - A single, high dose of idarubicin combined with cytarabine as induction therapy
      for adult patients with recurrent or refractory acute lymphoblastic leukemia.
AB  - BACKGROUND: The majority of adult patients who are treated for lymphoblastic
      disease will either develop recurrent disease or will be refractory to their
      initial therapy. One option for patients with recurrent/refractory disease is to
      administer a reinduction regimen that employs a dose-intense combination of
      anthracycline and cytarabine. These salvage regimens are relatively distinct from
      the traditional vincristine/prednisone-based programs that are used typically as
      primary induction therapy. The authors studied a regimen that contained high-dose
      cytarabine and a single high dose of idarubicin as salvage induction therapy for
      patients with recurrent or refractory lymphoblastic disease. METHODS: Twenty-nine
      previously treated adult patients with recurrent or refractory acute
      lymphoblastic leukemia were treated with a new intensive regimen. Eight patients
      had primary refractory disease. Twenty-one patients had recurrent disease, and 16
      of these patients developed recurrent disease while they were still receiving
      their primary therapy. The treatment regimen consisted of cytarabine 3.0 g/m(2)
      by 3-hour infusion daily for 5 days and idarubicin 40 mg/m(2) given as a single
      dose on Day 3. Filgrastim (granulocyte-colony stimulating factor) 5 microg/kg
      administered subcutaneously every 12 hours was started on Day 7 and was continued
      until the absolute neutrophil count was > 5000/microL. Response was assessed
      using standard criteria. RESULTS: There were 11 complete responses (38%; 95%
      confidence interval, 20-56%). Four patients subsequently underwent allogeneic
      bone marrow transplantation. Moderate but acceptable toxicity was observed given
      the severely myelosuppressive nature of the regimen. There was only one treatment
      related death (3%). Two patients, both with significant prior exposure to
      anthracyclines, suffered reductions in left ventricular function to the 20-30%
      range during episodes of severe systemic infection. After recovery from
      infection, the ejection fraction in one patient improved to 50%. CONCLUSIONS: The
      authors conclude that this regimen has moderate activity and a relatively low
      incidence of mortality for this high-risk group of patients. This regimen may be
      most suitable for patients who can undergo potentially curative allogeneic bone
      marrow transplantation if they achieve a complete response.

PMID- 12209752
TI  - Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with
      portal vein tumor thrombosis: analysis of 48 cases.
AB  - BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) with
      portal vein tumor thrombosis (PVTT) is extremely poor. The aim of this study was
      to elucidate the efficacy of hepatic arterial infusion chemotherapy (HAIC) for
      patients with advanced HCCs. METHODS: Forty-eight HCC patients with PVTT were
      treated by HAIC via a subcutaneously implanted injection port. Of these, 14 had
      PVTT in the second portal branch and 34 patients had PVTT in the first portal
      branch or in the main portal trunk. One course of chemotherapy consisted of daily
      cisplatin (7 mg/m(2) for 1 hour on Days 1-5) followed by 5-fluorouracil (170
      mg/m(2) for 5 hours on Days 1-5). Patients were scheduled to receive four serial
      courses of HAIC. Responders were defined as having either a complete response
      (CR) or partial response (PR) and nonresponders were defined as exhibiting stable
      disease or progressive disease. The prognosis after HAIC and factors related to
      survival were analyzed. RESULTS: Following HAIC, 4 and 19 patients exhibited a CR
      and PR, respectively (response rate = 48%). The 1, 2, 3, and 5-year cumulative
      survival rates of 48 patients treated with HAIC were 45%, 31%, 25%, and 11%,
      respectively. Median survival periods for 23 responders and 25 nonresponders were
      31.6 (range, 8.3-76.9) months and 5.4 (1.9-29.0) months, respectively.
      Therapeutic effect (P < 0.001) and hepatic reserve capacity (P = 0.021) were
      identified as significant prognostic factors by univariate analysis. Multivariate
      analysis identified only therapeutic effect as being significantly related to
      survival. CONCLUSIONS: HAIC using low-dose cisplatin and 5-fluorouracil may be a
      useful therapeutic option for patients with advanced HCC with PVTT. HCC patients
      with PVTT who respond to HAIC could certainly have survival benefits.

PMID- 12209753
TI  - Usefulness of tumor pressure as a prognostic factor in cases of hepatocellular
      carcinoma where the diameter of the tumor is 3 cm or less.
AB  - BACKGROUND: The current study was designed to determine the usefulness of
      pretreatment tumor pressure as a new prognostic factor in patients with small
      hepatocellular carcinoma (HCC; 3 cm or smaller in diameter). METHODS: The study
      included 39 patients with small HCC in whom tumor pressure was determined. They
      underwent percutaneous ethanol (with Lipiodol) injection therapy (Lp-PEI) or
      transcatheter arterial embolization (TAE) of the hepatic artery. Tumor pressure
      was determined percutaneously under ultrasonographic guidance. The factors
      analyzed were age, gender, mean blood pressure, the presence/absence of antibody
      to hepatitis C virus (anti-HCV), alcohol abuse, Child's classification, the
      presence/absence of esophagogastric varices, serum alpha-fetoprotein (AFP) level,
      tumor size, number of tumors, degree of tumor differentiation, the
      presence/absence of tumor capsule, tumor pressure, and the method of treatment.
      Multivariate analysis using Cox proportional hazards model was conducted on the
      factors that may have affected prognosis (P < 0.25) according to the univariate
      analysis using a proportional hazards model. RESULTS: The rates of local and
      distant recurrence were higher (P < 0.01, P < 0.01, respectively) and the
      survival rate was lower (P = 0.03) in patients with high tumor pressure than in
      those with low tumor pressure. Multivariate analysis revealed that tumor pressure
      (P < 0.01), AFP level (P = 0.01), and age (P = 0.01) were significant predictive
      factors associated with local recurrence. Tumor pressure (P < 0.01) and AFP level
      (P < 0.01) were both significantly associated with distant recurrence. The only
      significant predictive factor associated with survival rate was tumor pressure (P
      < 0.04). CONCLUSIONS: The current study revealed that tumor pressure was
      associated significantly with survival rates after Lp-PEI or TAE in patients with
      small HCC. There were also significant predictive factors associated with local
      recurrence, these being tumor pressure, AFP level, and age, and with distant
      recurrence, namely, tumor pressure and AFP level. Tumor pressure measured before
      the initial treatment of patients with small HCC may be a useful new prognostic
      factor.

PMID- 12209754
TI  - Brain metastases in locally advanced nonsmall cell lung carcinoma after
      multimodality treatment: risk factors analysis.
AB  - BACKGROUND: Brain metastases (BM) are frequent sites of initial failure in
      patients with locally advanced nonsmall cell lung cancer (LAD-NSCLC) undergoing
      multimodality treatments (MMT). New treatment and follow-up strategies are needed
      to reduce the risk of BM and to diagnose them early enough for effective
      treatment. METHODS: The incidence rate of BM as the first site of recurrence in
      112 patients with LAD-NSCLC treated with the same MMT protocol was calculated.
      The influence of patient, disease, and treatment-related factors on the incidence
      of BM and on the time-to-brain recurrence (TBR) was analyzed. RESULTS: BM as the
      first site of failure was observed in 25 cases (22% of the study population and
      29% of all recurrences). In 18 of those cases, the brain was the exclusive site
      of recurrence. Median TBR was 9 months. The 2-year actuarial incidence of BM was
      29%. Central nervous system (CNS) recurrence was more common in patients younger
      than 60 years (P = 0.006) and in whom bulky (> or = 2 cm) mediastinal lymph nodes
      were present (P = 0.02). TBR was influenced by age (P = 0.004) and by bulky lymph
      node disease (P = 0.003). Multivariate analysis confirmed the prognostic role of
      age, whereas the presence of clinical bulky mediastinal lymph nodes was of
      borderline significance. CONCLUSIONS: Our study confirmed a high rate of BM in
      patients with LAD-NSCLC submitted to MMT. Most of these CNS recurrences were
      isolated and occurred within 2 years of initial diagnosis. Age younger than 60
      years was associated with an increased risk of BM and reduced TBR, whereas the
      presence of clinical bulky mediastinal lymph nodes was of borderline
      significance. Although our data require further validation in future studies, our
      results suggest that additional trials on prophylactic cranial irradiation and on
      intensive radiologic follow-up should focus on these high-risk populations.

PMID- 12209755
TI  - Standards of care for anemia management in oncology: focus on lung carcinoma.
AB  - BACKGROUND: Anemia is common in patients with lung carcinoma, particularly among
      those undergoing platinum-based cytotoxic chemotherapy. Evidence is growing that
      anemia can have a profound impact on the patient's quality of life, often
      manifested as the patient's inability to function normally. METHODS: A literature
      review was conducted to provide a current picture of the incidence and impact of
      anemia in patients with lung carcinoma and the usage and limitations of current
      treatment. RESULTS: The incidence of anemia (a hemoglobin [Hb] level < 11g/dL) in
      lung carcinoma patients is approximately 50-60%, varying according to treatment
      regimen. However, despite evidence supporting the treatment of anemia, many
      clinicians only intervene when Hb levels fall below 8 g/dL. This may be because
      of a lack of awareness of the incidence and impact of anemia on cancer patients,
      but most likely is because of limitations of current treatment options (blood
      transfusion and recombinant human erythropoietin [epoetin-alpha]). Darbepoetin
      alpha represents a new generation of erythropoiesis-stimulating proteins.
      Biochemically distinct from epoetin-alpha, darbepoetin-alpha has a greater sialic
      acid content and biologic half-life than epoetin-alpha, but stimulates
      erythropoiesis in the same manner. Clinical trials involving patients with cancer
      related anemia have shown that darbepoetin-alpha has a threefold longer half-life
      than epoetin-alpha, which may allow less frequent dosing. The results from an
      ongoing clinical trial dedicated to testing the clinical benefits of darbepoetin
      alpha in treating anemia in lung carcinoma patients will provide a valuable
      insight into its full potential in this setting. CONCLUSIONS: Anemia is common
      but is reported to be undertreated in patients with lung carcinoma. The
      introduction of darbepoetin-alpha into clinical practice may overcome some of the
      limitations of current treatments and facilitate improvement in the management of
      cancer-related anemia.

PMID- 12209756
TI  - Expression and alteration of ras and p53 proteins in patients with lung carcinoma
      accompanied by idiopathic pulmonary fibrosis.
AB  - BACKGROUND: The ras oncogene and the p53 tumor suppressor gene play important
      roles in the carcinogenic process of lung carcinoma. The authors evaluated
      whether alterations of the ras and p53 proteins may contribute to the development
      of lung carcinoma in patients with idiopathic pulmonary fibrosis (IPF) and
      whether such alterations may explain the high incidence of lung carcinoma among
      patients with IPF. METHODS: Lung tissues were obtained from 35 patients who had
      IPF without complications of lung carcinoma and from 36 patients who had IPF with
      complications of lung carcinoma. Altered expression of ras and p53 proteins was
      evaluated by immunohistochemistry, and mutations of both genes were evaluated by
      polymerase chain reaction-single strand conformation polymorphism and sequencing
      analyses. RESULTS: The frequency of expression of ras protein in type II alveolar
      pneumocytes was significantly greater in lung tissues from patients with IPF who
      had lung carcinoma compared with lung tissues from patients with IPF who did not
      have lung carcinoma (75% vs. 40%, respectively; P < 0.01). K-ras point mutation
      in codon 12 (GGT to GTT transversion) was detected in lung tissue with
      interstitial pneumonia, in which ras protein was overexpressed in type II
      alveolar pneumocytes obtained from 2 of 41 patients with IPF complicated by lung
      carcinoma, causing amino acid substitution (Gly to Val) in both patients. A p53
      mutation was detected in three of six lung tissue samples from patients who had
      IPF lung with positive p53 immunoreactivity, and multiple mutations were detected
      in two samples. CONCLUSIONS: Expression of ras protein in type II alveolar
      pneumocytes and mutation in the codon 12 of K-ras gene in lung tissue may
      contribute to the induction of lung carcinoma in patients with IPF. Furthermore,
      the presence of multiple mutations in the p53 gene may explain the high incidence
      lung carcinoma in patients with IPF.

PMID- 12209757
TI  - Evaluation of the proliferation marker MIB-1 in the prognosis of cutaneous
      malignant melanoma.
AB  - BACKGROUND: The proliferation marker MIB-1, which recognizes the Ki-67 antigen,
      provides independent prognostic information in several tumor types. Its utility
      in melanoma has been evaluated mostly in studies of thick primary tumors. Its
      usefulness in thinner lesions has not been assessed adequately. METHODS: A well
      characterized cohort of 137 patients diagnosed with primary cutaneous melanoma at
      the New York University School of Medicine between 1972 and 1982 was studied
      based on the availability of representative tissues and adequate clinical follow
      up. Twenty-one tumors were less than or equal to 1.0 mm thick, 94 were between
      1.01 and 4.0 mm thick, and 22 were thicker than 4.0 mm. Tumor cell proliferation
      was assessed by immunohistochemistry using the monoclonal antibody MIB-1. MIB-1
      expression was correlated with baseline clinicopathologic parameters, as well as
      recurrence (RR), disease-free (DFS), and overall survival (OS) rates. Median
      follow-up among survivors was 6.5 years (range, 5.6-17.5). RESULTS: High
      proliferative index, defined as 20% or more of tumor cells showing nuclear
      immunoreactivity, was observed in 65 of 137 (47.4%) cases. High proliferative
      index was significantly correlated with increased tumor thickness (P < 0.001) and
      higher stage (P = 0.03). Trends approaching statistical significance were
      observed with ulceration of the primary tumor (P = 0.09), male gender (P = 0.06),
      and shorter DFS (P = 0.12). No significant associations were seen between high
      proliferative index and RR or OS. In multivariate analyses, tumor thickness was
      the strongest predictor of clinical outcome. CONCLUSIONS: In primary cutaneous
      melanoma, a high proliferative index is associated with clinicopathologic
      parameters predictive of worse clinical outcomes. However, it was not an
      independent predictor of clinical outcome.

PMID- 12209758
TI  - Evaluation of the efficiency of chemotherapy in in vivo orthotopic models of
      human glioma cells with and without 1p19q deletions and in C6 rat orthotopic
      allografts serving for the evaluation of surgery combined with chemotherapy.
AB  - BACKGROUND: Malignant gliomas of the central nervous system remain associated
      with dismal prognoses because of their diffuse invasion of the brain parenchyma.
      Very few experimental models that mimic clinical reality are available today to
      test potentially new therapies. The authors set up experimental in vivo glioma
      models of anaplastic astrocytomas of human and rat origins and anaplastic
      oligodendroglioma of human origin. Standard hospital chemotherapies were employed
      to test the validity of these models. METHODS: Three glioma cells lines obtained
      from the American Type Culture Collection (i.e., human Hs683 and U373 cells and
      rat C6 cells) were implanted into nude mouse brains (Hs683 and U373 cells) and
      rat brains (C6 cells). The astrocytic nature, as opposed to the oligodendrocytic
      nature, of the Hs683 and U373 models was investigated by using quantitative
      (computer-assisted microscopy) immunohistochemical characterizations of nestin,
      vimentin, glutathione-S-transferase alpha (GSTalpha), GSTmu, GSTpi, and p53
      expression. Comparative genomic hybridization (CGH) was employed to investigate
      1p19q losses. Chronic administrations of carmustine (BCNU), fotemustin, or
      temozolomide were assayed in the xenografted U373 and Hs683 models. Both BCNU
      related chemotherapy and surgery were assayed in the C6 model. RESULTS: The
      quantitative phenotypic analyses pointed to the oligodendroglial nature of the
      Hs683 cell line and the astrocytic nature of the U373 cell line. The Hs683 cells
      exhibited 1p19q losses, whereas the U373 cells did not. BCNU, fotemustin, and
      temozolomide dramatically increased the time of survival of the Hs683
      oligodendroglioma-bearing mice, whereas temozolomide only induced a weak but
      nevertheless statistically significant increase in the U373 glioma-bearing mice.
      In the C6 rat glioma model, surgery and BCNU chemotherapy were more efficient
      than either treatment alone. CONCLUSIONS: The in vivo models of gliomas of the
      central nervous system developed in the current work best mimicked clinical
      reality. They can be used either to identify new therapies against human gliomas
      or to optimize existing therapies.

PMID- 12209759
TI  - Quantitative measurement of post-irradiation neck fibrosis based on the young
      modulus: description of a new method and clinical results.
AB  - BACKGROUND: Postirradiation fibrosis is one of the most common late effects of
      radiation therapy for patients with head and neck carcinoma. An objective and
      quantitative method for its measurement is much desired, but the criteria
      currently used to score fibrosis are mostly semiquantitative and partially
      subjective. METHODS: The Young Modulus (YM) is a physical parameter that
      characterizes the deformability of material to stress. The authors measured the
      YM in soft tissues of the neck, at defined reference points, using an ultrasound
      probe and computer algorithm that quantified the indentation (deformation) on
      tissue due to a measured, applied force. One hundred five patients who had
      received previous radiation therapy to the entire neck were assessed, and the
      results were compared with the hand palpation scores and with a functional
      parameter represented by the range of neck rotation, and all results were
      correlated with symptoms. RESULTS: The YM was obtained successfully in all
      patients examined. It had a significant positive correlation with the palpation
      score and a significant negative correlation with the range of neck rotation. The
      YM was significantly higher on the side of the neck that received a boost dose of
      radiation, although the corresponding palpation scores were similar. The results
      of all three measurement methods were correlated with symptoms. CONCLUSIONS:
      Postirradiation neck fibrosis can be measured in absolute units based on the YM.
      The results showed a significant correlation with hand palpation scores, with
      restriction of neck rotation, and with symptoms. Compared with the palpation
      method, the YM is more quantitative, objective, focused on small subregions, and
      better discriminates regions subject to differential radiation dose levels. Its
      inclusion in the Analytic category of the Late Effects of Normal Tissues-SOMA
      system should be considered to facilitate comparative studies.

PMID- 12209760
TI  - Clinical importance of serum interleukin-18 and nitric oxide activities in breast
      carcinoma patients.
AB  - BACKGROUND: Interleukin-18 (IL-18) is a novel immunoregulatory cytokine that was
      known previously as interferon-gamma-inducing factor. IL-18 levels can be used as
      a serum indicator for monitoring the clinical course of patients with hematologic
      malignancies and gastric carcinoma. Nitric oxide (NO) is a pleiotropic molecule
      that participates in the multistep processing of carcinogenesis. METHODS: In the
      current study, we measured serum IL-18 and nitrate and nitrite levels in 38
      metastatic and 26 nonmetastatic breast carcinoma patients and 16 healthy control
      subjects. Serum nitrate and nitrite levels were measured as an index of NO
      generation. RESULTS: The levels of serum IL-18 and nitrate and nitrite were
      increased significantly in breast carcinoma patients compared with control
      subjects (P < 0.001). Serum IL-18 levels were significantly higher in the
      metastatic patients compared with the nonmetastatic patients (P < 0.001). There
      was no difference in serum nitrate and nitrite levels between metastatic and
      nonmetastatic patients (P > 0.05). Patients with bone metastasis have higher
      serum IL-18 levels and lower serum nitrate and nitrite levels compared with
      patients with liver, lung, and local metastasis (P < 0.001). There was no
      correlation among serum IL-18, nitrate and nitrite, CA 15-3, and carcinoembryonic
      antigen levels (P > 0.05). CONCLUSIONS: These findings suggest that serum IL-18
      and nitrate and nitrite levels may be useful markers in monitoring metastatic
      breast carcinoma patients. IL-18 and NO activities in breast carcinoma patients
      with bone metastasis may be more valuable in the follow-up of these patients.

PMID- 12209761
TI  - Pathologic evaluation of radical cystectomy specimens.

PMID- 12209762
TI  - Serum CYFRA 21-1 is one of the most reliable tumor markers for breast carcinoma.

PMID- 12209764
TI  - Clinical and histologic features of level 2 cutaneous malignant melanoma
      associated with metastasis.

PMID- 12209766
TI  - Hypothyroidism: a frequent event after radiotherapy for patients with head and
      neck carcinoma.

PMID- 12209768
TI  - Development of a large-scale biocalorimeter to monitor and control bioprocesses.
AB  - Calorimetry has shown real potential at bench-scale for chemical and biochemical
      processes. The aim of this work was therefore to scale-up the system by
      adaptation of a standard commercially available 300-L pilot-scale bioreactor. To
      achieve this, all heat flows entering or leaving the bioreactor were identified
      and the necessary instrumentation implemented to enable on-line monitoring and
      dynamic heat balance estimation. Providing that the signals are sufficiently
      precise, such a heat balance would enable calculation of the heat released or
      taken up during an operational (bio)process. Two electrical Wattmeters were
      developed, the first for determination of the power consumption by the stirrer
      motor and the second for determination of the power released by an internal
      calibration heater. Experiments were designed to optimize the temperature
      controller of the bioreactor such that it was sufficiently rapid so as to enable
      the heat accumulation terms to be neglected. Further calibration experiments were
      designed to correlate the measured stirring power to frictional heat losses of
      the stirrer into the reaction mass. This allows the quantitative measurement of
      all background heat flows and the on-line quantitative calculation of the
      (bio)process power. Three test fermentations were then performed with B.
      sphaericus 1593M, a spore-forming bacterium pathogenic to mosquitoes. A first
      batch culture was performed on a complex medium, to enable optimization of the
      calorimeter system. A second batch culture, on defined medium containing three
      carbon sources, was used to show the fast, accurate response of the heat signal
      and the ability to perfectly monitor the different growth phases associated with
      growth on mixed substrates, in particular when carbon sources became depleted. A
      maximum heat output of 1100 W was measured at the end of the log-phase. A fed
      batch culture on the same defined medium was then carried out with the feed rate
      controlled as a function of the calorimeter signal. A maximum heat output of 2250
      W was measured at the end of the first log-phase. This work demonstrates that
      real-time quantitative calorimetry is not only possible at pilot-scale, but could
      be readily applied at even larger scales. The technique requires simple, readily
      available devices for determination of the few necessary heat flows, making it a
      robust, cost-effective technique for process development and routine monitoring
      and control of production processes.

PMID- 12209769
TI  - Recovery and separation of cell lysate proteins using hydrogels guided by aqueous
      two-phase extraction principles.
AB  - The addition of poly(ethylene glycol) and salts to clarified cell lysates of
      Thiosphaera pantotropha increases sorption of microbial proteins into dextran
      hydrogels, consistent with the thermodynamics of aqueous two-phase extraction.
      Addition of 12 wt% PEG-10,000 to the lysate increased total sorption of protein
      by the dextran gel from 5.2 mg/g dextran to 37 mg/g; addition of either 0.1 M
      potassium iodide or tetrabutylammonium fluoride along with PEG to the lysate
      increased protein sorption to more than 63 mg/g, a 12-fold increase. SDS-PAGE
      demonstrated that the type of salt added controls which proteins are absorbed by
      the gel. Previously demonstrated only with model solutions, these results suggest
      another approach to recovery and separation strategies for proteins produced by
      fermentation.

PMID- 12209770
TI  - Integrated reactor concepts for the enzymatic kinetic synthesis of cephalexin.
AB  - Integrated process concepts for enzymatic cephalexin synthesis were investigated
      by our group, and this article focuses on the integration of reactions and
      product removal during the reactions. The last step in cephalexin production is
      the enzymatic kinetic coupling of activated phenylglycine (phenylglycine amide or
      phenylglycine methyl ester) and 7-aminodeacetoxycephalosporanic acid (7-ADCA).
      The traditional production of 7-ADCA takes place via a chemical ring expansion
      step and an enzymatic hydrolysis step starting from penicillin G. However, 7-ADCA
      can also be produced by the enzymatic hydrolysis of adipyl-7-ADCA. In this work,
      this reaction was combined with the enzymatic synthesis reaction and performed
      simultaneously (i.e., one-pot synthesis). Furthermore, in situ product removal by
      adsorption and complexation were investigated as means of preventing enzymatic
      hydrolysis of cephalexin. We found that adipyl-7-ADCA hydrolysis and cephalexin
      synthesis could be performed simultaneously. The maximum yield on conversion
      (reaction) of the combined process was very similar to the yield of the separate
      processes performed under the same reaction conditions with the enzyme
      concentrations adjusted correctly. This implied that the number of reaction steps
      in the cephalexin process could be reduced significantly. The removal of
      cephalexin by adsorption was not specific enough to be applied in situ. The
      adsorbents also bound the substrates and therewith caused lower yields.
      Complexation with beta-naphthol proved to be an effective removal technique;
      however, it also showed a drawback in that the activity of the cephalexin
      synthesizing enzyme was influenced negatively. Complexation with beta-naphthol
      rendered a 50% higher cephalexin yield and considerably less byproduct formation
      (reduction of 40%) as compared to cephalexin synthesis only. If adipyl-7-ADCA
      hydrolysis and cephalexin synthesis were performed simultaneously and in
      combination with complexation with beta-naphthol, higher cephalexin
      concentrations also were found. In conclusion, a highly integrated process (two
      reactions simultaneously combined with in situ product removal) was shown
      possible, although further optimization is necessary.

PMID- 12209771
TI  - Simulation of algae growth in a bench-scale bubble column reactor.
AB  - The growth of the marine red microalga Porphyridium sp. in a bubble-column
      photobioreactor was simulated. The proposed model constitutes a dynamic
      integration of the kinetics of photosynthesis and photoinhibition with the fluid
      dynamics of the bubble column, including the effects of shear stress on the
      kinetics of growth. The kinetic data used in the model were obtained in
      independent experiments run in a thin-film photobioreactor with defined
      light/dark cycles. The maintenance term was modified to take into account the
      effects of liquid flow in the bioreactor on the growth rate. A hybrid method
      proposed for the approximate solution of the equations gave an appreciable
      reduction of the calculation time. Extrapolations of the model indicated the
      possibility of predicting the optimal diameter for an assembly of bubble column
      photobioreactors. Satisfactory fit was found with the experimental results of
      biomass growth in a 13-liter bubble column.

PMID- 12209772
TI  - Selective separation of cis-trans geometrical isomers of beta-carotene via CO2
      supercritical fluid extraction.
AB  - We investigated a novel method for the selective separation of beta-carotene
      isomers from a freeze-dried powder of the algae Dunaliella bardawil using
      supercritical fluid extraction. The separation method relies on the different
      dissolution rate of the 9Z and all-E isomers of beta-carotene in SC-CO(2). At
      first, the equilibrium solubility of the two isomers in SC-CO(2) was determined
      at the extraction conditions of 44.8 MPa and 40 degrees C. The solubility of the
      9Z isomer was found to be nearly 4 times higher than that of the all-E isomer
      (1.92 x 10(-5) g all-E isomer/g CO(2) compared to 7.64 x 10(-5) g 9Z isomer/g
      CO(2)). When supercritical fluid extraction was applied to a carotenoid
      concentrate from the algae (29 wt% beta-carotene) or a freeze-dried powder of the
      algae (3.1% beta-carotene), a selective separation of the 9Z/all-E isomers of
      beta-carotene was obtained. Thirty-nine percent recovery of beta-carotene with
      80% purity of 9Z isomer was achieved at the initial stages of extraction (40 mL
      CO(2)). The extraction rate of beta-carotene from the freeze-dried algae powder
      was slower than that from the carotenoid concentrate, resulting in a reduction in
      the recovery and purity of the 9Z isomer. This indicates that even at the initial
      stage of the extraction the internal mass resistance is significant. Isomer
      purity and recovery could be enhanced upon grinding of the algae powder.

PMID- 12209773
TI  - Biodegradation of gasoline by gellan gum-encapsulated bacterial cells.
AB  - Encapsulated cell bioaugmentation is a novel alternative solution to in situ
      bioremediation of contaminated aquifers. This study was conducted to evaluate the
      feasibility of such a remediation strategy based on the performance of
      encapsulated cells in the biodegradation of gasoline, a major groundwater
      contaminant. An enriched bacterial consortium, isolated from a gasoline-polluted
      site, was encapsulated in gellan gum microbeads (16-53 microm diameter). The
      capacity of the encapsulated cells to degrade gasoline under aerobic conditions
      was evaluated in comparison with free (non-encapsulated) cells. Encapsulated
      cells (2.6 mg(cells) x g(-1) bead) degraded over 90% gasoline hydrocarbons
      (initial concentration 50-600 mg x L(-1)) within 5-10 days at 10 degrees C.
      Equivalent levels of free cells removed comparable amounts of gasoline (initial
      concentration 50-400 mg x L(-1)) within the same period but required up to 30
      days to degrade the highest level of gasoline tested (600 mg x L(-1)). Free cells
      exhibited a lag phase in biodegradation, which increased from 1 to 5 days with an
      increase in gasoline concentration (200-600 x mg L(-1)). Encapsulation provided
      cells with a protective barrier against toxic hydrocarbons, eliminating the
      adaptation period required by free cells. The reduction of encapsulated cell mass
      loading from 2.6 to 1.0 mg(cells) x g(-1) bead caused a substantial decrease in
      the extent of biodegradation within a 30-day incubation period. Encapsulated
      cells dispersed within the porous soil matrix of saturated soil microcosms
      demonstrated a reduced performance in the removal of gasoline (initial
      concentrations of 400 and 600 mg x L(-1)), removing 30-50% gasoline hydrocarbons
      compared to 40-60% by free cells within 21 days of incubation. The results of
      this study suggest that gellan gum-encapsulated bacterial cells have the
      potential to be used for biodegradation of gasoline hydrocarbons in aqueous
      systems.

PMID- 12209774
TI  - Glucose-to-fructose conversion at high temperatures with xylose (glucose)
      isomerases from Streptomyces murinus and two hyperthermophilic Thermotoga
      species.
AB  - The conversion of glucose to fructose at elevated temperatures, as catalyzed by
      soluble and immobilized xylose (glucose) isomerases from the hyperthermophiles
      Thermotoga maritima (TMGI) and Thermotoga neapolitana 5068 (TNGI) and from the
      mesophile Streptomyces murinus (SMGI), was examined. At pH 7.0 in the presence of
      Mg(2+), the temperature optima for the three soluble enzymes were 85 degrees C
      (SMGI), 95 degrees to 100 degrees C (TNGI), and >100 degrees C (TMGI). Under
      certain conditions, soluble forms of the three enzymes exhibited an unusual,
      multiphasic inactivation behavior in which the decay rate slowed considerably
      after an initial rapid decline. However, the inactivation of the enzymes
      covalently immobilized to glass beads, monophasic in most cases, was
      characterized by a first-order decay rate intermediate between those of the
      initial rapid and slower phases for the soluble enzymes. Enzyme productivities
      for the three immobilized GIs were determined experimentally in the presence of
      Mg(2+). The highest productivities measured were 750 and 760 kg fructose per
      kilogram SMGI at 60 degrees C and 70 degrees C, respectively. The highest
      productivity for both TMGI and TNGI in the presence of Mg(2+) occurred at 70
      degrees C, pH 7.0, with approximately 230 and 200 kg fructose per kilogram enzyme
      for TNGI and TMGI, respectively. At 80 degrees C and in the presence of Mg(2+),
      productivities for the three enzymes ranged from 31 to 273. A simple mathematical
      model, which accounted for thermal effects on kinetics, glucose-fructose
      equilibrium, and enzyme inactivation, was used to examine the potential for high
      fructose corn syrup (HFCS) production at 80 degrees C and above using TNGI and
      SMGI under optimal conditions, which included the presence of both Co(2+) and
      Mg(2+). In the presence of both cations, these enzymes showed the potential to
      catalyze glucose-to-fructose conversion at 80 degrees C with estimated lifetime
      productivities on the order of 2000 kg fructose per kilogram enzyme, a value
      competitive with enzymes currently used at 55 degrees to 65 degrees C, but with
      the additional advantage of higher fructose concentrations. At 90 degrees C, the
      estimated productivity for SMGI dropped to 200, whereas, for TNGI, lifetime
      productivities on the order of 1000 were estimated. Assuming that the most
      favorable biocatalytic and thermostability features of these enzymes can be
      captured in immobilized form and the chemical lability of substrates and products
      can be minimized, HFCS production at high temperatures could be used to achieve
      higher fructose concentrations as well as create alternative processing
      strategies.

PMID- 12209775
TI  - Sensitivity function-based model reduction: A bacterial gene expression case
      study.
AB  - Mathematical models used to predict the behavior of genetically modified
      organisms require 1). a (rather) large number of state variables, and 2).
      complicated kinetic expressions containing a large number of parameters. Since
      these models are hardly identifiable and of limited use in model-based
      optimization and control strategies, a generic methodology based on sensitivity
      function analysis is presented to reduce the model complexity at the level of the
      kinetics, while maintaining high prediction power. As a case study to illustrate
      the method and results obtained, the influence of the dissolved oxygen
      concentration on the cytN gene expression in the bacterium Azospirillum
      brasilense Sp7 is modeled. As a first modeling approach, available mechanistic
      knowledge is incorporated into a mass balance equation model with 3 states and 14
      parameters. The large differences in order of magnitude of the model parameters
      identified on the available experimental data indicate 1). possible structural
      problems in the kinetic model and, associated with this, 2). a possibly too high
      number of model parameters. A careful sensitivity function analysis reveals that
      a reduced model with only seven parameters is almost as accurate as the original
      model.

PMID- 12209776
TI  - Operational intensification by direct product sequestration from cell
      disruptates: application of a pellicular adsorbent in a mechanically integrated
      disruption-fluidised bed adsorption process.
AB  - A novel prototype adsorbent, designed for intensified fluidised bed adsorption
      processes, was assembled by the emulsification coating of 4% (w/v) porous agarose
      upon a zirconia-silica solid core. The adsorbent, designated ZSA (particle
      density 1.75 g/ml, maximum pellicle depth 40 microm), was subjected to physical
      and biochemical comparison with the performance of two commercial adsorbents
      (Streamline and Macrosorb K4AX). Bed expansion qualities and hydrodynamic
      characteristics (N, D(axl) and B(o)) of ZSA demonstrated a marked robustness in
      the face of elevated velocities (up to 550 cm/h) and biomass loading (up to 30%
      (ww/v)) disrupted yeast cells. Cibracron Blue derivatives of the pellicular
      prototype (ZSA-CB), evaluated in the batch and fluidised bed recovery of
      glyceraldehyde 3-phosphate dehydrogenase (G3PDH) from unclarified yeast
      disruptates, exhibited superior capacities and adsorption/desorption performance
      to the commercial derivatives. These advanced physical and biochemical properties
      facilitated a demonstration of the direct, mechanical coupling of bead-milling
      and fluidised bed adsorption in a fully integrated process for the accelerated
      recovery of G3PDH from yeast. The generic application of such pellicular
      adsorbents and integrated processes to the recovery of labile, intracellular
      products is discussed.

PMID- 12209778
TI  - General O-glycosylation of 2-furfuryl alcohol using beta-glucuronidase.
AB  - beta-Glucuronidase from bovine liver is able to catalyze transfer of several
      carbohydrates to furfuryl alcohol, an acid-sensitive diene, with transfer yields
      as high as 84%. Carbohydrates that were transferred in yields of 30% or higher
      include gluco-, galacto-, xylo-, and fucopyranose. Small variations in the
      configuration of the substrate hydroxyls lead to large variations in the
      catalytic behavior of the enzyme in terms of both the initial reaction velocities
      and the final ratios of transfer-to-hydrolysis. The high transfer yields and
      surprising nonspecificity towards carbohydrate suggest that the enzyme may be a
      versatile tool for the general O-glycosylation of dienic alcohols.

PMID- 12209777
TI  - Optical waveguide lightmode spectroscopy (OWLS) to monitor cell proliferation
      quantitatively.
AB  - The use of microscopic observations used for in situ monitoring of cell
      proliferation in the production of epidermal autografts is not satisfactory. In
      particular, the identification of the projected cell area from microscopic
      pictures by image analysis (IA) depends on intensity edges and level of contrasts
      and is thus limited to subconfluent cultures. Some of these problems can be
      solved by using optical waveguide lightmode spectroscopy (OWLS), which measures
      the effective refractive index of a thin layer above an Si(Ti)O(2) waveguide
      surface. In this study the use of OWLS to monitor cell adhesion, spreading, and
      growth was studied. The sensitivity of the method was investigated by using three
      different cell lines, two fibroblasts and one hepatoma cell line. Cell
      proliferation of two strains of fibroblasts and hepatoma cells was monitored up
      to 2 days with the OWLS. In parallel, cell density was determined at different
      time points microscopically using an additional window in the measuring chamber.
      The cell density of fully spread cells ( approximately 4 h after attachment) was
      found to be proportional to the OWLS signal. In long-term cultures the influence
      of the cell density from single cells to confluent cell cultures upon the OWLS
      signal was investigated. The exponentially growing number of hepatoma resulted in
      a linear increase of the sensor signal. Due to this and to the fact that the
      proliferating cells exhibit contact inhibition, it was concluded that the cell
      contact area must decrease exponentially. The results show the strength of OWLS
      for monitoring the adhesion and proliferation of anchorage-dependent cells in
      applications where an on-line indicator of the total biomass is needed.
      Additionally, OWLS provides metabolic information through detection of the cell
      mass in close contact with the waveguide.

PMID- 12209779
TI  - Macroaffinity ligand-facilitated three-phase partitioning (MLFTPP) for
      purification of xylanase.
AB  - It is shown that eudragit S-100, a copolymer of methylacrylic acid and
      methylmethacrylate, undergoes three-phase partitioning. It was found that 95%
      eudragit S-100 could be recovered as the interfacial precipitate by using 30%
      (w/v) ammonium sulfate, 1:1 ratio of t-butanol to polymer solution at 40 degrees
      C. Three-phase partitioning of proteins uses simultaneous addition of ammonium
      sulfate and t-butanol to precipitate proteins in an interfacial layer separating
      the aqueous phase and organic solvent. Exploiting the affinity of xylanases
      towards eudragit S-100, it was possible to purify xylanase from Aspergillus
      niger; 60% recovery of activity with 95-fold purification could be obtained by
      this process. The purified enzyme showed A single band on SDS-PAGE. The technique
      shows promise to develop into a general method that could be termed
      "macroaffinity ligand-facilitated three-phase partitioning (MLFTPP).

PMID- 12209780
TI  - Separating lysozyme from bacteriophage P22 in two-phase aqueous micellar systems.
AB  - This communication demonstrates that two-phase aqueous mixed (nonionic/ionic)
      micellar systems have the potential for improving the separation of proteins from
      viruses. Specifically, two separation experiments were performed to show that the
      addition of the anionic surfactant sodium dodecyl sulfate (SDS) to the two-phase
      aqueous nonionic n-decyl tetra(ethylene oxide) (C(10)E(4)) micellar system
      increases the yield of a model net positively charged protein, lysozyme, in the
      micelle-rich phase from 75 to 95%, while still maintaining approximately the same
      yield of a model net negatively charged virus, bacteriophage P22, in the micelle
      poor phase (97% vs. 98%).

PMID- 12209781
TI  - Production of L(+)-lactic acid from glucose and starch by immobilized cells of
      Rhizopus oryzae in a rotating fibrous bed bioreactor.
AB  - A rotating fibrous-bed bioreactor (RFB) was developed for fermentation to produce
      L(+)-lactic acid from glucose and cornstarch by Rhizopus oryzae. Fungal mycelia
      were immobilized on cotton cloth in the RFB for a prolonged period to study the
      fermentation kinetics and process stability. The pH and dissolved oxygen
      concentration (DO) were found to have significant effects on lactic acid
      productivity and yield, with pH 6 and 90% DO being the optimal conditions. A high
      lactic acid yield of 90% (w/w) and productivity of 2.5 g/L.h (467 g/h.m(2)) was
      obtained from glucose in fed-batch fermentation. When cornstarch was used as the
      substrate, the lactic acid yield was close to 100% (w/w) and the productivity was
      1.65 g/L.h (300 g/h.m(2)). The highest concentration of lactic acid achieved in
      these fed-batch fermentations was 127 g/L. The immobilized-cells fermentation in
      the RFB gave a virtually cell-free fermentation broth and provided many
      advantages over conventional fermentation processes, especially those with freely
      suspended fungal cells. Without immobilization with the cotton cloth, mycelia
      grew everywhere in the fermentor and caused serious problems in reactor control
      and operation and consequently the fermentation was poor in lactic acid
      production. Oxygen transfer in the RFB was also studied and the volumetric oxygen
      transfer coefficients under various aeration and agitation conditions were
      determined and then used to estimate the oxygen transfer rate and uptake rate
      during the fermentation. The results showed that the oxygen uptake rate increased
      with increasing DO, indicating that oxygen transfer was limited by the diffusion
      inside the mycelial layer.

PMID- 12209782
TI  - Controlled enzymatic removal of damaging casein layers on medieval wall
      paintings.
AB  - A new, gentle enzymatic method was developed for a controlled removal of casein
      layers from medieval wall paintings. These casein layers were applied over the
      last 60 years on wall paintings in order to decrease substantial damage due to a
      peeling off of the frescoes from the roughcast surface due to environmental
      effects. However, due to the aging of the casein layers (at 40-50 years), a more
      drastic peeling occurred and the danger of total destruction of the wall
      paintings is severe. Thus, screening was performed to find the most suitable
      enzyme for casein digestion. Alcalase 2.5 DX L was the most appropriate enzyme
      for an effective proteolysis reaction. The enzyme was immobilized on
      functionalized cellulose membrane. A membrane pad system with immobilized enzymes
      was developed which could be pressed on the casein layers on the wall painting. A
      controlled removal of the casein layers by proteolytic digestion was observed and
      it was possible to continuously wash off the hydrolyzed casein fragments from the
      wall painting surface by an aqueous carbonate buffer flowing through the membrane
      pad. The removal and the digestion was monitored by reverse HPLC. Additionally,
      an on-line monitoring system was set up in order to continuously follow the
      casein layer removal and the digestion procedure directly on the wall painting.
      This technique is based on noninvasive 2D-fluorescence monitoring. Optical fiber
      systems were used to continuously monitor the fluorescence intensity of casein
      bound tryptophan. The off-line data were verified with the on-line 2D
      fluorescence data. Based on the scientific result an appropriate technique for
      the controlled enzymatic removal of damaging casein layers on the surface of
      medieval wall paintings using immobilized enzyme is now available. It is now
      applied to remove such casein layers from medieval wall paintings in the
      Allerheiligen-Kapelle Cloister, Wienhausen, Germany, and the St. Alexander
      Kirche, Wildeshausen, Germany.

PMID- 12209783
TI  - Production of D-amino acid oxidase (DAO) of Trigonopsis variabilis in
      Schizosaccharomyces pombe and the characterization of biocatalysts prepared with
      recombinant cells.
AB  - The cDNA of D-amino acid oxidase (DAO) gene isolated from Trigonopsis variabilis
      was expressed in Schizosaccharomyces pombe. A clone, ASP327-10, transformed with
      plasmid vector, pTL2M5DAO, expressed catalytically active DAO in the presence of
      G418, and converted Cephalosprin C to alpha-ketoadipyl-7-cephalosporanic acid (KA
      7-ACA) and glutaryl-7-aminocephalosporanic acid (GL-7-ACA). Biocatalysts were
      prepared using ASP327-10 and T. variabilis, and evaluated to demonstrate the
      feasibility of recombinant S. pombe for industrial application. The cells were
      immobilized by crosslinking polyethylene imine after glutardialdehyde (GDA)
      fixation and permeabilization by alkaline treatment. Although the biocatalyst
      prepared from ASP327-10 exhibited DAO activity, catalase activity still remained
      fully even after permeabilization, under which condition, the catalase activity
      of T. variabilis decreased to 20-30%. Heat treatment was required before cell
      fixation by GDA to inactivate the catalase in S. pombe. This improved the
      efficiency of bioconversion to GL-7-ACA, but caused poor mechanical strength in
      the biocatalyst of S. pombe. To overcome this weakness, a catalase-deficient host
      strain was obtained by ethylmethansulfate mutagenesis. Moreover, taking economics
      into consideration, the integrative vector, pTL2M5DAO-8XL, with multi-copies of
      expression cassette was constructed to express DAO in S. pombe even in the
      absence of G418. The newly established integrant, ASP417-7, did not exhibit any
      catalase activity so that heat treatment was not required. The obtained integrant
      and its biocatalyst were significantly improved in GL-7ACA conversion ability and
      mechanical strength. This study demonstrates that the established integrant is a
      potential candidate as an alternative source of DAO enzyme.

PMID- 12209784
TI  - Pilot-scale production of (S)-styrene oxide from styrene by recombinant
      Escherichia coli synthesizing styrene monooxygenase.
AB  - Recombinant Escherichia coli JM101(pSPZ10) cells produce the styrene
      monooxygenase of Pseudomonas sp. strain VLB120, which catalyzes the oxidation of
      styrene to (S)-styrene oxide at an enantiomeric excess larger than 99%. This
      biocatalyst was used to produce 388 g of styrene oxide in a two-liquid phase 30-L
      fed-batch bioconversion. The average overall volumetric activity was 170 U per
      liter over a period of more than 10 h, equivalent to mass transfer rates of 10.2
      mmoles per liter per hour at a phase ratio of 0.5. At this transfer rate, the
      biotransformation system appeared to be substrate mass-transfer limited. The
      reactor had an estimated power input in the order of 5 W. L(-1), which is close
      to values typically obtained with commercially operating units. The product could
      be easily purified by fractional distillation to a purity in excess of 97%. The
      process illustrates the feasibility of recombinant whole cell biotransformations
      in two-liquid phase systems with toxic substrates and products.

PMID- 12209785
TI  - The use of microscale processing technologies for quantification of biocatalytic
      Baeyer-Villiger oxidation kinetics.
AB  - Microscale processing techniques would be a useful tool for the rapid and
      efficient collection of biotransformation kinetic data as a basis for bioprocess
      design. Automated liquid handling systems can reduce labor intensity while the
      small scale reduces the demand for scarce materials such as substrate, product,
      and biocatalyst. Here we illustrate this concept by establishing the use of
      several microwell formats (96-round, 96-deep square and 24-round well microtiter
      plates) for quantification of the kinetics of the E. coli TOP10 [pQR239] resting
      cell catalyzed Baeyer-Villiger oxidation of bicyclo[3.2.0]hept-2en-6-one using
      glycerol as a source of reducing power. By increasing the biocatalyst
      concentration until the biotransformation rate was oxygen mass-transfer limited
      we can ensure that kinetic data collected are in the region away from oxygen
      limitation. Using a 96-round well plate the effect of substrate
      (bicyclo[3.2.0]hept-2en-6-one) concentration on the volumetric CHMO activity was
      examined and compared to data collected from 1.5-L stirred-tank experiments. The
      phenomenon and magnitude of substrate inhibition, observed at the larger scale,
      was accurately reproduced in the microwell format. We have used this as an
      illustrative example to demonstrate that under adequately defined conditions,
      automated microscale processing technologies can be used for the collection of
      quantitative kinetic data. Additionally, by using the experimentally determined
      stoichiometry for product formation and glycerol oxidation, we have estimated the
      maximum oxygen transfer rates as a function of well geometry and agitation rate.
      Oxygen-transfer rates with an upper limit of between 33 mmol. L(-1). h(-1) (based
      solely on product formation) and 390 mmol. L(-1). h(-1) (based on product
      formation and glycerol oxidation) were achieved using a 96-square well format
      plate shaken at 1300 rpm operated with a static surface area to volume ratio of
      320 m(2). m(-3).

PMID- 12209786
TI  - Development of a novel diffusion-based method to estimate the size of the
      aggregated Abeta species responsible for neurotoxicity.
AB  - beta-Amyloid peptide (Abeta) is the primary protein component of senile plaques
      in Alzheimer's disease and is believed to be responsible for the
      neurodegeneration associated with the disease. Abeta is toxic only when
      aggregated, however, the size and structure of the aggregated species associated
      with toxicity is unknown. In the present study, we developed a diffusion-based
      method to simultaneously separate and detect the biological activity of toxic
      Abeta oligomers and used the method to examine the relationship between size of
      aggregated protein and toxicity to SH-SY5Y cells. From these measurements, the
      effective diffusivity and hydrodynamic radius of the toxic oligomeric species of
      Abeta could be determined. A sensitivity analysis was performed to examine the
      effects of model assumptions used in data analysis on the effective diffusivity
      calculated. The method provides a new estimate of the size of small toxic Abeta
      species associated with fibril formation. This work contributes to our
      understanding of the relationship between Abeta structure and toxicity and with
      further refinements may aid in our ability to design agents which alter the Abeta
      aggregation/dissociation processes associated with neurotoxicity.

PMID- 12209787
TI  - High-throughput screening and quantitative structure-efficacy relationship models
      of potential displacer molecules for ion-exchange systems.
AB  - A technique is presented for the high-throughput screening of ion-exchange
      displacers. Potential displacers were employed to displace proteins in parallel
      batch ion-exchange experiments. The percentage of protein displaced from a
      particular stationary phase was then used as a parameter to rank the displacers.
      By employing this technique, a large number of molecules possessing a range of
      affinities and properties could be rapidly evaluated. This data was then used
      together with traditional and electron density-based transferable atom equivalent
      (TAE) molecular descriptors computed for the displacer molecules to produce
      quantitative structure-efficacy relationship (QSER) models using a genetic
      algorithm/partial least squares (GA/PLS) regression approach. The QSER models
      were generated using a portion of the protein-displacement data, with the
      remainder serving as a test set. Descriptor selection and model building was
      accomplished using a genetic algorithm/partial least squares approach. The
      resulting models were found to have high-correlation coefficients and could be
      used to accurately predict the behavior of molecules not included in the training
      set. In addition, the models were employed to examine a virtual library of
      displacers based on modifications of neomycin to provide further insight into
      displacer design. The results presented here indicate that it may be possible to
      design displacers that can dramatically improve the effective selectivity of ion
      exchange chromatographic materials.

PMID- 12209788
TI  - Determination of oxygen gradients in engineered tissue using a fluorescent
      sensor.
AB  - Nutrient and oxygen supply of cells are crucial to tissue engineering in general.
      If a sufficient supply cannot be maintained, the development of the tissue will
      slow down or even fail completely. Previous studies on oxygen supply have focused
      on measurement of oxygen partial pressures (pO(2)) in culture media or described
      the use of invasive techniques with spatially limited resolution. The
      experimental setup described here allows for continuous, noninvasive, high
      resolution pO(2) measurements over the cross-section of cultivated tissues.
      Applying a recently developed technique for time-resolved pO(2) sensing using
      optical sensor foils, containing luminescent O(2)-sensitive indicator dyes, we
      were able to monitor and analyze gradients in the oxygen supply in a tissue over
      a 3-week culture period. Cylindrical tissue samples were immobilized on top of
      the sensors. By measuring the luminescence decay time, two-dimensional pO(2)
      distributions across the tissue section in contact with the foil surface were
      determined. We applied this technique to cartilage explants and to tissue
      engineered cartilage. For both tissue types, changes were detected in
      monotonously decreasing gradients of pO(2) from the surface with high pO(2) to
      minimum pO(2) values in the center of the samples. Nearly anoxic conditions were
      observed in tissue constructs ( approximately 0 Torr) but not in excised
      cartilage discs ( approximately 20 Torr) after 1 day. Furthermore, the oxygen
      supply seemed to strongly depend on cell density and cell function. Additionally,
      histological analysis revealed a maximum depth of approximately 1.3 mm of regular
      cartilage development in constructs grown under the applied culture conditions.
      Correlating analytical and histological analysis with the oxygen distributions,
      we found that pO(2) values below 11 Torr might impair proper tissue development
      in the center. The results illustrate that the method developed is an ideal one
      to precisely assess the oxygen demand of cartilage cultures.

PMID- 12209789
TI  - Interplay of SOS induction, recombinant gene expression, and multimerization of
      plasmid vectors in Escherichia coli.
AB  - Using pBR322- and pUC-derived plasmid vectors, a homologous (Escherichia coli
      native esterase) and three heterologous proteins (human interleukin-2, human
      interleukin-6, and Zymomonas levansucrase) were synthesized in E. coli
      IC2015(recA::lacZ) and GY4786 (sfiA::lacZ) strains. Via time-course measurement
      of beta-galactosidase activity in each recombinant culture, the SOS induction was
      estimated in detail and the results were systematically compared. In recombinant
      E. coli, the SOS response did not happen either with the recombinant insert
      negative plasmid backbone alone or the expression vectors containing the
      homologous gene. Irrespective of gene expression level and toxic activity of
      synthesized foreign proteins, the SOS response was induced only when the
      heterologous genes were expressed using a particular plasmid vector, indicating
      strong dependence on the recombinant gene clone and the selection of a plasmid
      vector system. It is suggested that in recombinant E. coli the SOS response
      (i.e., activation of recA expression and initial sfiA expression) may be related
      neither to metabolic burden nor toxic cellular event(s) by synthesized
      heterologous protein, but may be provoked by foreign gene-specific interaction
      between a foreign gene and a plasmid vector. Unlike in E. coli XL1-blue(recA(-))
      strains used, all expression vectors encoding each of the three heterologous
      proteins were multimerized in E. coli IC2015 strains in the course of
      cultivation, whereas the expression vectors containing the homologous gene never
      formed the plasmid multimers. The extent of multimerization was also dependent on
      a foreign gene insert in the expression vector. As a dominant effect of the SOS
      induction, recombinant plasmid vectors used for heterologous protein expression
      appear to significantly form various multimers in the recA(+) E. coli host.

PMID- 12209790
TI  - Optimization of recombinant protein expression level in Escherichia coli by flow
      cytometry and cell sorting.
AB  - Overexpression of recombinant proteins in Escherichia coli often leads to a
      severe growth retardation of the host cells. The phage T7 promoter phi10 in a pET
      vector was utilized to express human superoxide dismutase. Induction with IPTG
      lead to an increase in protein content and cell size and a termination of cell
      division, due to the deviation of the general metabolic fluxes from all cellular
      processes to plasmid maintenance and foreign protein synthesis. To generate
      promoter mutants which are better tolerated by the host cells we constructed a
      random mutation library by PCR with degenerated primers in a part of the promoter
      involved in the binding to the RNA polymerase and the initiation of
      transcription. This library was sorted by flow cytometry for cells with a lower
      total protein content as an indicator for continued cell replication and hence a
      less severe stress situation. The clones obtained had a similar SOD production
      compared to the original strain, but were able to reach higher densities in a
      batch culture, which resulted in a higher total yield.

PMID- 12209791
TI  - Yield prediction and stoichiometry of multi-step biodegradation reactions
      involving oxygenation.
AB  - Microorganisms can initiate the degradation of organic compounds by oxygenation
      reactions that require the investment of energy and electrons. This diversion of
      energy and electrons away from synthesis reactions leads to decreased overall
      cell yields. A thermodynamic method was developed that improves the accuracy of
      cell yield prediction for compounds degraded through pathways involving
      oxygenation reactions. This method predicts yields and stoichiometry for each
      step in the biodegradation pathway, thus enabling modeling a multi-step
      biodegradation process in which oxygenations occur and intermediates may persist.
      EDTA and benzene biodegradation are presented as examples. The method compares
      favorably with other yield prediction methods while providing additional
      information of yields for intermediates produced in the degradation pathway.

PMID- 12209792
TI  - The potential for establishment of axial temperature profiles during solid-state
      fermentation in rotating drum bioreactors.
AB  - The mixing and heat transfer phenomena within rotating drum bioreactors (RDBs)
      used for solid-state fermentation processes are poorly studied. The potential for
      the establishment of axial temperature gradients within the substrate bed was
      explored using a heat transfer model. For growth of Aspergillus oryzae on wheat
      bran within a 24 L RDB with air at a superficial velocity of 0.0023 m s(-1) and
      15% relative humidity, the model predicts an axial gradient between the air inlet
      and outlet of 2 degrees C during rapid growth, compared to experimental axial
      temperature gradients of between 1 and 4 degrees C. Undesirably high temperatures
      occur throughout the bed under these operating conditions, but the model predicts
      that good temperature control can be achieved using humid air (90% relative
      humidity) at superficial velocities of 1 m s(-1) for a 204 L RDB. For a 2200 L
      RDB, good temperature control is predicted with superficial velocities as low as
      0.4 m s(-1) with the airflow being switched from 90% to 15% relative humidity
      whenever the temperature at the outlet end of the drum exceeds the optimal
      temperature for growth. This work suggests that significant axial temperature
      gradients can arise in those RDBs that lack provision for axial mixing. It is
      therefore advisable to use angled lifters within RDBs to promote axial mixing.

PMID- 12209793
TI  - A functional genomics approach using metabolomics and in silico pathway analysis.
AB  - In the field of functional genomics increasing effort is being undertaken to
      analyze the function of orphan genes using metabolome data. Improved analytical
      equipment allows screening simultaneously for a high number of metabolites. Such
      metabolite profiles are analyzed using multivariate data analysis techniques and
      changes in the genotype will in many cases lead to different metabolite profiles.
      Here, a theoretical framework that may be applied to identify the function of
      orphan genes is presented. The approach is based on a combination of metabolome
      analysis combined with in silico pathway analysis. Pathway analysis may be
      carried out using convex analysis and a change in the active pathway structure of
      deletion mutants expressed in a different metabolite profile may disclose the
      function or the functional class of an orphan gene. The concept is illustrated
      using a simplified model for growth of Saccharomyces cerevisiae.

PMID- 12209794
TI  - Overexpression of an archaeal protein in yeast: secretion bottleneck at the ER.
AB  - Archaeal enzymes have great potential for industrial use; however, expressing
      them in their natural hosts has proven challenging. Growth conditions for many
      archaea are beyond typical fermentation capabilities, and to compound the
      problem, archaea generally achieve much lower biomass yields than Escherichia
      coli or Saccharomyces cerevisiae. To determine whether a eukaryotic host, S.
      cerevisiae, would be a suitable alternative for archaeal protein production, we
      examined the expression of the tetrameric beta-glucosidase from the
      hyperthermophilic archaeon Pyrococcus furiosus. We engineered the beta
      glucosidase to facilitate secretion into the culture medium and have demonstrated
      the beta-glucosidase's secretion and activity. We determined the dependence of
      beta-glucosidase secretion on gene copy number and obtained a transformant
      capable of secreting approximately 10 mg/L in batch culture. All transformants
      retained large intracellular fractions of beta-glucosidase, indicative of an
      intracellular bottleneck. Cell fractionation by sucrose density centrifugation
      and immunofluorescence identified the endoplasmic reticulum as the secretion
      bottleneck. Preliminary evidence indicates that the cause of this bottleneck is
      misfolding of the monomeric beta-glucosidase, rather than tetrameric association.
      Expression at moderately elevated temperatures (between 30 and 40 degrees C)
      improved beta-glucosidase yields, suggesting that higher temperature expression
      may improve folding and secretion yields.

PMID- 12209795
TI  - Self-activating factor X derivative fused to the C-terminus of a cellulose
      binding module: Production and properties.
AB  - In this work, a new derivative of FX was engineered. It comprises a cellulose
      binding module (CBM) fused to the N-terminus of the truncated light chain (E2FX)
      of FX and a hexahistidine tag (H6) fused to the C-terminus of the heavy chain.
      The sequence LTR at the site of cleavage of the activation peptide from the N
      terminus of the heavy chain is changed to IEGR to render the derivative self
      activating. However, N-linked glycans on the CBM of the derivative blocked its
      binding to cellulose and those on the activation peptide slowed its activation.
      Therefore, the sites of N-linked glycosylation on the CBM and on the activation
      peptide were eliminated by mutation. The final derivative can be produced in good
      yield by cultured mammalian cells. It is purified easily with Ni(2+)-agarose, it
      is self-activating, and it can be immobilized on cellulose. When immobilized on a
      column of cellulose beads, the activated derivative retains approximately 80% of
      its initial activity after 30 days of continuous hydrolysis of a fusion protein
      substrate. Under these conditions of operation, the effective substrate:enzyme
      ratio is >10(4).

PMID- 12209796
TI  - Screening for peptide affinity ligands on CIM monoliths.
AB  - Screening of peptide ligands for affinity chromatography usually involves
      incubation with the target protein in a batch system. In an additional step,
      peptides with fast binding kinetics have to be selected in respect to
      satisfactory performance under flow conditions on a support ensuring optimal
      three-dimensional presentation of the peptide. We have developed a rapid
      screening system based on peptide synthesis and screening on CIM((R)) disks. The
      disk size was minimized to fit into microplates usually applied for solid-phase
      extraction. In combination with a vacuum manifold, semi-automated peptide
      synthesis and screening for binding to a target protein under simulated
      chromatography conditions are possible. Various analytical methods can be applied
      for parallel and automated determination of the quantity, integrity, or activity
      of the target protein in the flow through or bound to the affinity support. This
      system also allows parallel screening for suitable chromatographic conditions
      like running buffer, washing, and elution conditions.

PMID- 12209797
TI  - Modeling aerobic carbon source degradation processes using titrimetric data and
      combined respirometric-titrimetric data: experimental data and model structure.
AB  - Experimental data are presented that resulted from aerobic batch degradation
      experiments in activated sludge with simple carbon sources (acetate and dextrose)
      as substrates. Data collection was done using combined respirometric-titrimetric
      measurements. The respirometer consists of an open aerated vessel and a closed
      non-aerated respiration chamber for monitoring the oxygen uptake rate related to
      substrate degradation. The respirometer is combined with a titrimetric unit that
      keeps the pH of the activated sludge sample at a constant value by addition of
      acid and/or base. The experimental data clearly showed that the activated sludge
      bacteria react with consumption or production of protons during aerobic
      degradation of the two carbon sources under study. Thus, the cumulative amount of
      added acid and/or base could serve as a complementary information source on the
      degradation processes. For acetate, protons were consumed during aerobic
      degradation, whereas for dextrose protons were produced. For both carbon sources,
      a linear relationship was found between the amount of carbon source added and the
      amount of protons consumed (in case of acetate: 0.38 meq/mmol) or produced (in
      case of dextrose: 1.33 meq/mmol) during substrate degradation. A model taking
      into account substrate uptake, CO(2) production, and NH(3) uptake for biomass
      growth is proposed to describe the aerobic degradation of a C(x)H(y)O(z)-type
      carbon source. Theoretical evaluation of this model for reference parameters
      showed that the proton effect due to aerobic substrate degradation is a function
      of the pH of the liquid phase. The proposed model could describe the experimental
      observations with both carbon sources.

PMID- 12209798
TI  - Modeling aerobic carbon source degradation processes using titrimetric data and
      combined respirometric-titrimetric data: structural and practical
      identifiability.
AB  - The structural and practical identifiability of a model for description of
      respirometric-titrimetric data derived from aerobic batch substrate degradation
      experiments of a C(x)H(y)O(z) carbon source with activated sludge was evaluated.
      The model processes needed to describe titrimetric data included substrate
      uptake, CO(2) production, and NH(3) uptake for biomass growth. The structural
      identifiability was studied using the Taylor series method and a recently
      proposed generalization method. It showed that combining respirometric and
      titrimetric data allows structural identifiability of one extra parameter
      combination, the biomass yield, Y(H), compared to estimation on separate data
      sets, on condition that the nitrogen fraction in biomass (i(XB)) is known.
      However, data from short-term batch substrate degradation experiments were not
      sufficiently informative to allow practical identification of all structurally
      identifiable parameters. Combining respirometry and titrimetry resulted in
      improvements of parameter confidence intervals compared to estimation on separate
      respirometric or titrimetric data sets. However, the level of the improvement
      seems to be substrate dependent: parameter confidence intervals improved
      considerably more for dextrose than for acetate degradation models. Noteworthy is
      the finding that the half-saturation substrate concentrations can be different
      depending on whether they are estimated from respirometric or titrimetric data.
      Moreover, this difference appears to be dependent on the carbon source
      considered: for dextrose, titrimetry-based K(S) values are higher than
      respirometry-based values while for acetate the opposite was found. It was
      hypothesized that this can be explained by the different point in cell metabolism
      where the proton production or consumption takes place, leading to a
      corresponding difference in timing between pH effect and oxygen consumption.
      Finally, the biomass yield Y(H) and the nitrogen content of the biomass i(XB)
      could be estimated from combined respirometric-titrimetric data obtained with
      addition of a known amount of carbon source. Y(H) can also be estimated from r(O)
      data when the initial substrate concentration S(S)(0) is known. The values found
      correspond to values reported in literature, but, interestingly, also seem able
      to reflect the occurrence of storage processes when pulses of acetate and
      dextrose are added.

PMID- 12209799
TI  - Hydrolysis of wheat starch and its effect on the falling number procedure:
      mathematical model.
AB  - A population balance model was developed for wheat starch hydrolysis to simulate
      the performance parameters of a viscosity-based device, known as the Falling
      Number instrument. The instrument is widely used as an indirect means to gauge
      the level of preharvest sprout activity in cereal grains such as wheat and
      barley. The model consists of three competing kinetics: starch gelatinization,
      enzymatic hydrolysis, and enzyme thermal deactivation. Using established
      principles of starch rheology and fluid mechanics, the model simulates the
      velocity profiles of the falling stirrer, starch gel viscosity, and the Falling
      Number readings at various levels of alpha-amylase. Model predictions for the
      velocity of the stirrer at any time during the downward fall, as well as the
      prediction of the total time needed for the fall, defined as the Falling Number,
      were in fair agreement with experimental measurements. There was better agreement
      between the modeled viscosity and the final viscosity of the starch gel as
      measured by a precision rheometer than there was with the measured Falling
      Number.

PMID- 12209800
TI  - Fractional precipitation of plasmid DNA from lysate by CTAB.
AB  - Preparative-scale purification of plasmid DNA has been attempted by diverse
      methods, including precipitation with solvents, salts, and detergents and
      chromatography with ion-exchange, reversed-phase, and size-exclusion columns.
      Chromatographic methods such as hydrophobic interaction chromatography (HIC),
      reversed phase chromatography (RPC), and size exclusion chromatography (SEC) are
      the only effective means of eliminating the closely related relaxed and denatured
      forms of plasmid as well as endotoxin to acceptable levels. However, the
      anticipated costs of manufacturing-scale chromatography are high due to (a) large
      projected volumes of the high-dosage therapeutic molecule and (b) restricted
      loading of the large plasmid molecule in the pores of expensive resins. As an
      alternative to chromatography, we show herein that precipitation with the
      cationic detergent, cetyltrimethylammonium bromide (CTAB), is effective for
      selective precipitation of plasmid DNA from proteins, RNA, and endotoxin.
      Moreover, CTAB affords novel selectivity by removal of host genomic DNA and even
      the more closely related relaxed and denatured forms of plasmid as earlier,
      separate fractions. Finally, plasmid that has been precipitated by CTAB can be
      purified by selectively dissolving under conditions of controlled salt
      concentration. The selectivity mechanism is most likely based upon conformational
      differences among the several forms of DNA. As such, CTAB precipitation provides
      an ideal nonchromatographic capture step for the manufacture of plasmid DNA.

PMID- 12209801
TI  - High-activity enzyme-polyurethane coatings.
AB  - The synthesis of water-borne polyurethane coatings in the presence of
      diisopropylfluorophosphatase (DFPase, E.C. 3.8.2.1) enabled the irreversible
      attachment of the enzyme to the polymeric matrix. The distribution of immobilized
      DFPase as well as activity retention are homogeneous within the coating. The
      resulting enzyme-containing coating (ECC) film hydrolyzes
      diisopropylfluorophosphate (DFP) in buffered media at high rates, retaining
      approximately 39% intrinsic activity. Decreasing ECC hydrophilicity, via the use
      of a less hydrophilic polyisocyanate during polymerization, significantly
      enhanced the intrinsic activity of the ECC. DFPase-ECC has biphasic deactivation
      kinetics, where the initial rapid deactivation of DFPase-ECC leads to the
      formation of a hyperstable and active form of enzyme.

PMID- 12209802
TI  - Computer-aided real-time estimation of reaction conversion for lipase-catalyzed
      esterification in solvent-free systems.
AB  - Real-time conversion estimation through macroscopic balancing was investigated
      for enzymatic esterification reactions in a solvent-free system. In principle,
      the conversion of ester synthesis can be determined from the amount of water
      produced by the reaction because water is formed as a by-product in the same
      molar ratio as the product. In this study, we show that the water production
      rate, and thereby the reaction conversion, can be estimated on-line from
      measurements of the relative humidity of the inlet and outlet air and the
      material balances of water in the system. In order to test the performance of the
      real-time conversion estimation method, the lipase-catalyzed esterification
      reaction of n-capric acid and n-decyl alcohol in solvent-free media was conducted
      while controlling the water activity at various values. When the reaction
      conversions estimated on-line were compared with those analyzed off-line by gas
      chromatography, good agreement was obtained: the average mean absolute error was
      +/- 2.4% of the reaction conversion despite the simplicity of the method. The on
      line estimation method presented here requires no expensive or complicated
      analytical instruments and no sampling of reaction medium. It can be used for
      monitoring nonaqueous enzymatic reactions where water is produced or consumed
      during reaction.

PMID- 12209803
TI  - Pattern analysis techniques to process fermentation curves: application to
      discrimination of enological alcoholic fermentations.
AB  - In fermentation processes, kinetic curves are generally aimed at control
      purposes. However, these curves could also contain information about inherent
      features of the product (such as origin, quality, etc.). This article presents
      several pattern analysis techniques used to classify fermentation curves. An
      application to alcoholic fermentation is presented as an illustration: it aims at
      retrieving the origin of a must from its fermentation curve. The fermentation
      kinetics of five vineyard musts, harvested over 9 years on the same parcels, were
      recorded. From these curves two sets of variables were generated: The first
      (p(1)) gathers all the kinetic curve points. The second (p(2)) contains a
      restrained number of variables, generated by the expert knowledge of the
      enologist. The set p(2) was processed by two very different techniques: a linear
      one (factorial discriminant analysis) and a nonlinear one (artificial neural
      networks). The set p(1) was processed by a new chemometric technique, the
      discriminant partial least-squares regression. For all the sets and the
      techniques used the selection of variables was studied. The interest in the
      latter is largely demonstrated both by theoretical and practical discussions. The
      discrimination results (up to 94% of good predictions) enhance the interest of
      the on-line measurements and their use in such pattern analysis tools.

PMID- 12209804
TI  - Purification of plasmid DNA by an integrated operation comprising tangential flow
      filtration and nitrocellulose adsorption.
AB  - There is an increasing interest in the development of scaleable and reproducible
      plasmid DNA purification protocols for vaccine and gene therapy. The use of an
      integrated unit operation, comprising tangential flow microfiltration coupled
      with the adsorption of contaminants onto nitrocellulose membranes as a single
      processing step was examined in this work. Experiments were performed using a
      custom-built tangential flow microfiltration rig (membrane area=12.5 cm(2)).
      Tangential flow filtration-adsorption of E. coli lysates containing a plasmid
      product removed most solids (>75%) and decreased chromosomal DNA contamination by
      75% w/w. Total plasmid DNA concentration and supercoiled content of the permeate
      were virtually identical to those of the feed, indicating a recovery yield of
      100% (transmission equal to 1). Results were similar for E. coli lysates
      containing either a 6.9 kb or a 20 kb plasmid. Significant reductions in RNA,
      endotoxin, and protein levels were also observed. The reproducibility and
      potential for scale up of this integrated filtration-adsorption operation makes
      it at attractive option for intermediate- to large-scale pharmaceutical-grade
      plasmid processing.

PMID- 12209805
TI  - Enhancement of a two-phase partitioning bioreactor system by modification of the
      microbial catalyst: demonstration of concept.
AB  - Application of two-phase partitioning bioreactors (TPPB) to the degradation of
      phenol and xenobiotics has been limited by the fact that many organic compounds
      that would otherwise be desirable delivery solvents can be utilized by the
      microorganisms employed. The ability to metabolize the solvent itself could
      interfere with xenobiotic degradation, limiting remediation efficiency, and hence
      represents a microbial characteristic incompatible with process goals. To avoid
      the issue of bioavailability, previous TPPB applications have relied on complex
      and often expensive delivery solvents or suboptimal catalyst-solvent pairings. In
      an effort to enhance TPPB activity and applicability, a genetically engineered
      derivative of Pseudomonas putida ATCC 11172 mutated in its ability to utilize
      medium-chain-length alcohols was generated (AVP2) and applied as the catalyst
      within a TPPB system with decanol as the delivery solvent. Kinetic analysis
      verified that the genetic alteration had not negatively affected phenol
      degradation. The volumetric productivity of AVP2 (0.48 g/L x h(-1)) was
      equivalent to that seen for wild-type ATCC 11172 (0.51 g/L x h(-1)), but a
      comparison of initial cell concentrations and yields revealed an improved phenol
      degrading efficiency for the mutant under process conditions. Yield coefficients,
      cell dry weight, and viable count determinations all confirmed the stability of
      the modified phenotype. This work illustrates the possibilities for TPPB process
      enhancement through a careful combination of genetic modification and solvent
      selection.

PMID- 12209806
TI  - Balancing GFP reporter plasmid quantity in large-scale transient transfections
      for recombinant anti-human Rhesus-D IgG1 synthesis.
AB  - Using transient expression, high amounts (>20 mg/mL) of secreted anti-human
      Rhesus-D IgG1 were produced in a suspension-adapted HEK293 EBNA cell line
      (Meissner et al., Biotechnol Bioeng 75: 197-203, 2001). Time of harvest was 3
      days after transfection. For the estimation of transfection efficiencies, we
      routinely co-transfected EGFP reporter DNA. At higher reporter plasmid
      concentrations, >2% of total transfecting plasmid DNA, a substantial reduction of
      recombinant antibody synthesis, was observed. This phenomenon was investigated in
      detail by co-expressing various green fluorescent protein (GFP) reporter
      constructs, which were targeted at different subcellular locations. Enhanced and
      humanized GFPs targeted to either the endoplasmic reticulum, the cytosol, or the
      nucleus reduced recombinant antibody production by 30 to 40% when present at
      higher concentrations in the transfection solution. The most severe effects were
      observed when the co-transfected EGFP was targeted to the endoplasmic reticulum,
      leading to a reduction of up to 80% in the presence of only 5% of reporter DNA.
      Interestingly, one nuclear-targeted GFP variant that was not codon optimized for
      expression in human cell lines could be added, to up to almost half of the total
      amount of transfecting DNA, without adverse effect on antibody production.
      Although the minimum amount of this reporter DNA needed for fluorescence reading
      was 10 times higher than for the other variants, it provided a much broader
      quantity range within which the transfection process could be studied without
      being negatively affected.

PMID- 12209807
TI  - Bioprocess applications of a Sindbis virus-based temperature-inducible expression
      system.
AB  - The production and study of toxic proteins requires inducible expression systems
      with low basal level expression and high inducibility. Here, we describe
      bioprocess applications of the pCytTS temperature-regulatable Sindbis virus
      replicon-based expression system. We used green fluorescent protein as a marker
      protein to optimize the selection of stable transfected clones with increased
      expression levels. Using the optimized protocol, clones were constructed that
      produced the growth-inhibiting, anti-viral protein interferon beta (beta-IFN).
      Selected clones were analyzed for temperature-dependent beta-IFN production in
      adherent and suspension cultures in serum free medium. Specific expression levels
      were around 1.0 x 10(5) IU/10(6) cells/day (0.5 microg/10(6) cells/day) in
      suspension cultures and over 1.5 x 10(6) IU/mL/day (7.5 microg/mL/day) in hollow
      fiber reactors using adherent cells. Hexahistidine-tagged beta-IFN purified from
      T-flask cultures was highly glycosylated and showed high specific activity. beta
      IFN mRNA amplified by the viral replicase for 10 days did not show an
      accumulation of mutations. These data suggest the applicability of the pCytTS
      inducible expression system for the production of high-quality glycoproteins in
      different reactors.

PMID- 12209808
TI  - Characterization of acid catalytic domains for cellulose hydrolysis and glucose
      degradation.
AB  - Cellulolytic enzymes consist of a catalytic domain, a linking peptide, and a
      binding domain. The paper describes research on carboxylic acids that have
      potential as catalytic domains for constructing organic macromolecules for use in
      cellulose hydrolysis that mimic the action of enzymes. The tested domains consist
      of the series of mono-, di-, and tricarboxylic acids with a range of pK(a)'s.
      This paper systematically characterizes the acids with respect to hydrolysis of
      cellobiose, cellulose in biomass, and degradation of glucose and compares these
      kinetics data to dilute sulfuric acid. Results show that acid catalyzed
      hydrolysis is proportional to H+ concentration. The tested carboxylic acids did
      not catalyze the degradation of glucose while sulfuric acid catalyzed the
      degradation of glucose above that of water alone. Consequently, overall yields of
      glucose obtained from cellobiose and cellulose are higher for the best carboxylic
      acid tested, maleic acid, when compared to sulfuric acid at equivalent solution
      pH.

PMID- 12209809
TI  - p27Kip1-mediated controlled proliferation technology increases constitutive sICAM
      production in CHO-DUKX adapted for growth in suspension and serum-free media.
AB  - We have engineered dihydrofolate reductase-deficient (dhfr(-)) Chinese hamster
      ovary (CHO)-DUKX B11 cells adapted for growth in serum-free suspension cultures
      for unlinked muristerone-inducible expression of the cyclin-dependent kinase
      inhibitor p27Kip1 and constitutive expression of the soluble intercellular
      adhesion molecule-1 (sICAM), a potent common cold therapeutic. Conditional
      overexpression of p27Kip1 resulted in a sustained G1-specific growth arrest of
      transgenic CHO-DUKX associated with up to fivefold-increased specific sICAM
      productivity. Herein we exemplify the implementation of controlled proliferation
      technology in a major biopharmaceutical production cell line that is compatible
      with key requirements for large-scale production procedures, including
      constitutive transgene expression and anchorage-independent growth in serum-free
      media.

PMID- 12209810
TI  - Use of frozen bagged seed inoculum for secondary metabolite and bioconversion
      processes at the pilot scale.
AB  - Frozen bagged seed inoculum was prepared, thawed and tested for seven cultures.
      Thawing techniques were developed and other key influences on thawing rate were
      quantified; seed bag thawing without a water bath rarely required more than 4 to
      5 h and was as short as 0.5 to 1 h for lower fill volume bags. Testing included
      growth of bagged seed as a function of bag fill volume (0.5, 1.0, 2.0, and 3.5
      L), comparison of culture age at time of bagging, growth of bagged versus
      laboratory-prepared seed, productivity of production cultures derived from bagged
      versus laboratory-prepared seed, growth of bagged seed as a function of volume
      percent glycerol added at time of bagging, and growth of bagged seed as a
      function of frozen storage time and temperature. For each culture tested,
      conditions were developed such that seed tanks inoculated with bagged seed showed
      only minimal delay in attaining the target oxygen uptake rate (OUR) relative to
      seed tanks inoculated with laboratory-prepared inoculum. Although the bag fill
      volume did influence culture growth in some cases, bag fill volumes required were
      reasonable (typically 2.0 to 3.5 L) compared with laboratory seed inoculum
      volumes of 2.0 L. In the most remarkable example, frozen bagged seed was prepared
      from a second-stage seed-tank cultivation of Glarca lozoyensis, then thawed and
      inoculated into first-stage seed medium. It grew to the desired OUR in a similar
      timeframe as laboratory-prepared inoculum inoculated into first-stage seed
      medium. Thus, the frozen bagged seed replaced an existing laboratory inoculum
      preparation period of 7 days without an appreciable delay in either of the two
      subsequent seed-tank growth stages. Furthermore, productivities were found to be
      comparable for bagged-seed-derived and laboratory-seed-derived production
      cultivations for four different fermentation processes.

PMID- 12209811
TI  - Advantages of continuous over batch reactors for the kinetic analysis of enzymes
      inhibited by an unknown substrate impurity.
AB  - A new experimental technique, employing a continuous stirred-tank reactor, for
      studying enzyme kinetics in the presence of inhibitor-contaminated substrate is
      described. The proposed method is simulated mathematically for competitive,
      uncompetitive, and mixed-type noncompetitive inhibition. The step-by-step
      experimental procedure is described, as is the necessary data analysis for
      determining the kinetic parameters. Differences in system response for enzyme
      inhibition by excess substrate and by an impurity are illustrated, and a
      stability analysis of the system is performed.

PMID- 12209812
TI  - Mathematical analysis of solid-liquid mass transfer in a batch reactor for the
      enzymatic transformation of testosterone to 4AD.
AB  - A previous mathematical analysis of mass transfer in a two-phase (solid-liquid)
      batch reactor for enzymatic transformation of testosterone to 4AD (Pereira et
      al., 1987) is extended to incorporate the effect of convective mixing. The
      results of the analysis showed that for a given enzyme loading, the mass transfer
      resistance in the solid (a function of the bead size) and the intensity of
      convective mixing (as embodied in the mass transfer coefficient) are two
      parameters that can be varied such that the overall mass transfer rate from the
      solid to the liquid phase ensures optimal reactor performance.

PMID- 12209813
TI  - Water and glucose gradients in the substrate measured with NMR imaging during
      solid-state fermentation with Aspergillus oryzae.
AB  - Gradients inside substrate particles cannot be prevented in solid-state
      fermentation. These gradients can have a strong effect on the physiology of the
      microorganisms but have hitherto received little attention in experimental
      studies. We report gradients in moisture and glucose content during cultivation
      of Aspergillus oryzae on membrane-covered wheat-dough slices that were calculated
      from (1)H-NMR images. We found that moisture gradients in the solid substrate
      remain small when evaporation is minimized. This is corroborated by predictions
      of a diffusion model. In contrast, strong glucose gradients developed. Glucose
      concentrations just below the fungal mat remained low due to high glucose uptake
      rates, but deeper in the matrix glucose accumulated to very high levels.
      Integration of the glucose profile gave an average concentration close to the
      measured average content. On the basis of published data, we expect that the
      glucose levels in the matrix cause a strong decrease in water activity. The
      results demonstrate that NMR can play an important role in quantitative analysis
      of water and glucose gradients at the particle level during solid-state
      fermentation, which is needed to improve our understanding of the response of
      fungi to this nonconventional fermentation environment.

PMID- 12209814
TI  - Mass transfer effects on the reaction rate for heterogeneously distributed
      immobilized yeast cells.
AB  - Here we examine the efficiency of different immobilized cell gradients applied to
      immobilized Saccharomyces cerevisiae fermenting glucose to ethanol. We developed
      a simulation model to fully study the competing effects of mass transfer
      hindrance and kinetics. It is based on a diffusion-reaction model and can be used
      to analyze the different cell concentration profiles inside an immobilized gel
      bead, in terms of effectiveness factors, productivity, and mass flux. The
      internal diffusion coefficient, which varies with the local cell concentration,
      as well as the external mass transfer, is taken into account when describing the
      efficiency. Although the diffusion hindrance is greater at higher cell
      concentrations, high cell concentration is still advantageous in the present case
      because the increase in reaction rate outweighs the diffusion hindrance. Thus,
      high cell concentrations contribute to increased productivity. The influence of
      the cell concentration gradient on the efficiency of the beads is negligible.
      Within the range of cell profiles studied it has been established that the
      location of the cells within the bead is of lesser importance. However, a steep
      cell gradient increases the importance of the external mass transfer.

PMID- 12209815
TI  - Rapid sampling for analysis of in vivo kinetics using the BioScope: a system for
      continuous-pulse experiments.
AB  - In this article we present a novel device, the BioScope, which allows elucidation
      of in vivo kinetics of microbial metabolism via perturbation experiments. The
      perturbations are carried out according to the continuous-flow method. The
      BioScope consists of oxygen permeable silicon tubing, connected to the fermentor,
      through which the broth flows at constant velocity. The tubing has a special
      geometry (serpentine channel) to ensure plug flow. After leaving the fermentor,
      the broth is mixed with a small flow of perturbing agent. This represents the
      start of the perturbation. The broth is sampled at different locations along the
      tubing, corresponding to different incubation times. The maximal incubation time
      is 69 s; the minimally possible time interval between the samples is 3-4 s.
      Compared to conventional approaches, in which the perturbation is carried out in
      the fermentor, the BioScope offers a number of advantages. (1) A large number of
      different perturbation experiments can be carried out on the same day, because
      the physiological state of the fermentor is not perturbed. (2) In vivo kinetics
      during fed-batch experiments and in large-scale reactors can be investigated. (3)
      All metabolites of interest can be measured using samples obtained in a single
      experiment, because the volume of the samples is unlimited. (4) The amount of
      perturbing agent spent is minimal, because only a small volume of broth is
      perturbed. (5) The system is completely automated. Several system properties,
      including plug-flow characteristics, mixing, oxygen and carbon dioxide transfer
      rates, the quenching time, and the reproducibility have been explored, with
      satisfactory results. Responses of several glycolytic intermediates in
      Saccharomyces cerevisiae to a glucose pulse, measured using a conventional
      approach are compared to results obtained with the BioScope. The agreement
      between the results demonstrates that the BioScope is indeed a promising device
      for studying in vivo kinetics.

PMID- 12209816
TI  - Integrated bioprocessing in Saccharomyces cerevisiae using green fluorescent
      protein as a fusion partner.
AB  - In this study, we examine the use of green fluorescent protein (GFP) for
      monitoring a hexokinase (HXK)-GFP fusion protein in Saccharomyces cerevisiae for
      various events including expression, degradation, purification, and localization.
      The fusion, HXK-EK-GFP-6 x His, was constructed where the histidine tag (6 x His)
      would allow for convenient affinity purification, and the enterokinase (EK)
      cleavage site would be used for separation of HXK from GFP after affinity
      purification. Our results showed that both HXK and GFP remained active in the
      fusion and, more importantly, that there was a linear correlation between HXK
      activity and GFP fluorescence. Enterokinase cleavage studies revealed that both
      GFP fluorescence intensity and HXK activity remained unchanged after separation
      of the fusion proteins, which indicated that fusion of GFP did not cause
      structural alteration of HXK and thus did not affect the enzymatic activity of
      HXK. We also found that degradation of the fusion protein occurred, and that
      degradation was limited to HXK with GFP remaining intact in the fusion. Confocal
      microscopy studies showed that while GFP was distributed evenly in the yeast
      cytosol, HXK-GFP fusion followed the correct localization of HXK, which resulted
      in a di-localization of both cytosol and the nucleus. GFP proved to be a useful
      fusion partner that may lead to the possibility of integrating the bioprocesses
      by quantitatively following the entire process visually.

PMID- 12209817
TI  - Supercritical fluid extraction of a lignocellulosic hydrolysate of spruce for
      detoxification and to facilitate analysis of inhibitors.
AB  - This work describes a novel approach to detoxify lignocellulosic hydrolysates and
      facilitate the analysis of inhibitory compounds, namely supercritical fluid
      extraction (SFE). The efficiency of the fermentation of lignocellulosic dilute
      acid hydrolysates depends upon the composition of the hydrolysate and the
      organism used. Furthermore, it has been shown that inhibitors in the hydrolysate
      reduce the fermentation yield. This knowledge has given rise to the need to
      identify and remove the inhibiting compounds. Sample clean-up or work-up steps,
      to provide a clean and concentrated sample for the analytical system, facilitate
      the characterization of inhibitors, or indeed any compound in the hydrolysates.
      Removal of inhibitors was performed with countercurrent flow supercritical fluid
      extraction of liquid hydrolysates. Three different groups of inhibitors (furan
      derivatives, phenolic compounds, and aliphatic acids) and sugars were
      subsequently analyzed in the hydrolysate, extracted hydrolysate, and extract. The
      effect of the SFE treatment was examined with respect to fermentability with
      Saccharomyces cerevisiae. Not only did the extraction provide a clean and
      concentrated sample (extract) for analysis, but also a hydrolysate with increased
      fermentability as well as lower concentrations of inhibitors such as phenolics
      and furan derivatives.

PMID- 12209818
TI  - A tribute to James E. Bailey.

PMID- 12209819
TI  - Jay Bailey as mentor--the students' perspective.
AB  - Professor James E. Bailey was not only a world-renowned leader and pioneer in
      biochemical engineering but also a mentor to the many graduate students and
      postdoctoral researchers in his group. To provide non-"Bailey-ites" with an
      impression of Jay as a mentor, we begin with a brief review of his career,
      focusing on the dynamics of the research group. Typical student experiences of
      being part of the Bailey group are then discussed, including the recognition of a
      particular research style and Jay's expectations for hard work. Finally, we
      provide some thoughts on Jay's mentoring style, which was marked by an ability to
      foster independence, a sense of quality, and passion for research. Jay's
      contributions as a mentor can perhaps be recognized as being as significant as
      his research achievements.

PMID- 12209820
TI  - Engineering of molecular and cellular biocatalysts: selected contributions by
      James E. Bailey.
AB  - James (Jay) E. Bailey was a pioneer in biotechnology and biochemical engineering.
      During his 30 years in academia he made seminal contributions to many fields of
      chemical engineering science, including catalysis and reaction engineering,
      bioprocess engineering, mathematical modeling of cellular processes, recombinant
      DNA technology, enzyme engineering, and metabolic engineering. This article
      celebrates some of his contributions to the engineering of molecular and cellular
      biocatalysts, and identifies the influence he had on current and future research
      in biotechnology.

PMID- 12209821
TI  - Cell-Surface display of heterologous proteins: From high-throughput screening to
      environmental applications.
AB  - A variety of expression systems for the display of either short peptides or fully
      folded proteins on E.coli and, to a lesser extent, on Gram-positive bacteria have
      been developed. The expression of proteins on the surface of microbial cells has
      proved extremely important for numerous applications ranging from combinatorial
      library screening and protein engineering, to whole cell biocatalysts and
      adsorbants for bioremediation purposes.

PMID- 12209822
TI  - A memorial review of Jay Bailey's contribution in prokaryotic metabolic
      engineering.
AB  - When mentioning prokaryotic metabolic engineering, most people will immediately
      think of Jay Bailey. Jay's contribution to this fast-growing field is evident and
      familiar to many. Therefore, instead of a detailed technical review, we attempt
      in this article to summarize his contribution and dissect reasons for his success
      in this area from a standpoint of one of his former students (VH) and of a
      colleague in the field (JCL). This short review is by no means complete and
      provides only a partial view of Jay's contribution to the metabolic engineering
      of prokaryotes.

PMID- 12209823
TI  - Metabolic engineering II. Eukaryotic systems.

PMID- 12209824
TI  - Analysis of fermentation processes using flow microfluorometry: Single-parameter
      observations of batch bacterial growth.
AB  - The laser flow microfluorometer (FMF) can determine the amounts of certain
      components in single cells at sample rates of several thousand cells per second.
      This technique has been employed to characterize Bacillus subtilis populations in
      batch fermentations with different inocula. Protein and nucleic acid
      distributions obtained by FMF analyses at different times during the batch have
      been decomposed using an optimized fit of summed subpopulation distributions. The
      results of these decomposition calculations, some of which have been
      approximately confirmed by independent microscopic observations, indicate that
      the relative numbers of single rods, cell chains, spores, and swollen rounded
      cells change dramatically during the entire fermentation including the stationary
      phase. The dynamics of these subpopulations may be related to secondary
      metabolite production.

PMID- 12209825
TI  - Structure-function relationships in immobilized chymotrypsin catalysis.
AB  - Specific activities and the amounts of active immobilized enzyme were determined
      for several different preparations of alpha-chymotrypsin immobilized on CNBr
      activated Sepharose 4B. Electron paramagnetic resonance (EPR) spectroscopy of
      free and immobilized enzyme with a spin label coupled to the active site was used
      to probe the effects of different immobilization conditions on the immobilized
      enzyme active site configuration. Specific activity of active enzyme decreased
      and rotational correlation time of the spin label increased with increasing
      immobilized enzyme loading. Enzyme immobilized using an intermediate six-carbon
      spacer arm exhibited greater specific activity and spin label mobility than
      directly coupled enzyme. The observed activity changes due to immobilization were
      completely consistent with corresponding active site structure alterations
      revealed by EPR spectroscopy.

PMID- 12209826
TI  - Analysis of growth rate effects on productivity of recombinant Escherichia coli
      populations using molecular mechanism models.
AB  - The influence of growth rate on Escherichia coli plasmid content and expression
      of a cloned-gene product has been described by a mathematical model based upon
      the molecular mechanism of lambdadv plasmid replication and known relationships
      between growth rate and transcription and translation activities of the host
      cell. The model simulates correctly decreases in plasmid content with increasing
      growth rate as observed experimentally for pBR322, NR1, R1, and Col E1 plasmids.
      A maximum with respect to growth rate in intracellular product accumulation is
      indicated by the model, as is a transient overshoot in product concentration
      following a shift from smaller to larger growth rate. Available data, although
      very limited, show the same trends. These results, obtained without parameter or
      kinetic form adjustments or manipulation, clearly illustrate the advantages of
      kinetic descriptions of recombinant systems based upon the pertinent molecular
      mechanisms.

PMID- 12209827
TI  - Intracellular expression of Vitreoscilla hemoglobin modifies microaerobic
      Escherichia coli metabolism through elevated concentration and specific activity
      of cytochrome o.
AB  - The function of the reversible oxygen-binding hemoprotein from Vitreoscilla
      (VHb), which enhances oxygen-limited cell growth and recombinant protein
      production when functionally expressed in Escherichia coli, was investigated in
      wild-type E. coli and in E. coli mutants lacking one of the two terminal
      oxidases, cytochrome o complex (aerobic terminal oxidase, Cyo) or cytochrome d
      complex (microaerobic terminal oxidase, Cyd). Deconvolution of VHb, cytochrome o,
      and cytochrome d bands from in vivo absorption spectra revealed a 5-fold
      enhancement in cytochrome o content and a 1.5-fold increment in cytochrome d by
      VHb under microaerobic environments (dissolved oxygen less than 2% air
      saturation). Based upon oxygen uptake kinetics measurements of these mutants, the
      apparent oxygen affinity of the Cyo(+), Cyd(-) E. coli was increased in the
      presence of VHb, but no difference in the apparent K(m) was observed for the Cyo(
      ), Cyd(+) strain. Results suggest that the expression of VHb in E. coli increases
      the level and activity of terminal oxidases and thereby improves the efficiency
      of microaerobic respiration and growth.

PMID- 12209828
TI  - Inverse metabolic engineering: a strategy for directed genetic engineering of
      useful phenotypes.
AB  - The classical method of metabolic engineering, identifying a rate-determining
      step in a pathway and alleviating the bottleneck by enzyme overexpression, has
      motivated much research but has enjoyed only limited practical success.
      Intervention of other limiting steps, of counter-balancing regulation, and of
      unknown coupled pathways often confounds this direct approach. Here the concept
      of inverse metabolic engineering is codified and its application is illustrated
      with several examples. Inverse metabolic engineering means the elucidation of a
      metabolic engineering strategy by: first, identifying, constructing, or
      calculating a desired phenotype; second, determining the genetic or the
      particular environmental factors conferring that phenotype; and third, endowing
      that phenotype on another strain or organism by directed genetic or environmental
      manipulation. This paradigm has been successfully applied in several contexts,
      including elimination of growth factor requirements in mammalian cell culture and
      increasing the energetic efficiency of microaerobic bacterial respiration.

PMID- 12209829
TI  - Engineering of coordinated up- and down-regulation of two glycosyltransferases of
      the O-glycosylation pathway in Chinese hamster ovary (CHO) cells.
AB  - Production of O-linked oligosaccharides that interact with selectins to mediate
      cell-cell adhesion occurs in one segment of a branched glycan biosynthesis
      network. Prior efforts to direct the branched pathway towards selectin-binding
      oligosaccharides by amplifying enzymes in this branch of the network have had
      limited success, suggesting that metabolic engineering to simultaneously inhibit
      the competing pathway may also be required. We report here the partial cloning of
      the CMP-sialic, acid:Galbeta1,3GalNAcalpha2,3-sialyltransferase (ST3Gal I) gene
      from Chinese hamster ovary (CHO) cells and the simultaneous inhibition of
      expression of CHO cell ST3Gal I gene and overexpression of the human UDP
      GlcNAc:Galbeta1,3GalNAc-R beta1,6-N-acetylglucosaminyltransferase (C2GnT) gene. A
      tetracycline-regulated system adjoined to tricistronic expression technology
      allowed "one-step" transient manipulation of multiple enzyme activities in the O
      glycosylation pathway of a previously established CHO cell line already
      engineered to express alpha1,3-fucosyltransferase VI (alpha1,3-Fuc-TVI).
      Tetracycline-regulated co-expression of a ST3Gal I fragment, cloned in the
      antisense orientation, and of C2GnT cDNA resulted in inhibition of the ST3Gal I
      enzymatic activity and increase in C2GnT activity which varied depending on the
      extent of tetracycline reduction in the cell culture medium. This simultaneous
      regulated inhibition and activation of the two key enzyme activities in the O
      glycosylation pathway of mammalian cells is an important addition to the
      metabolic engineering field.

PMID- 12209830
TI  - Development and distribution of the peptidergic system in larval and adult
      Patiriella: comparison of sea star bilateral and radial nervous systems.
AB  - Development of the larval peptidergic system in the sea star Patiriella regularis
      and structure of the adult nervous system in Patiriella species were documented
      in an immunofluorescence investigation using antisera to the sea star
      neuropeptide GFNSALMFamide 1 (S1) and confocal microscopy. P. regularis has
      planktotrophic development through bipinnaria and brachiolaria larvae. In early
      bipinnaria, two groups of immunoreactive cells appeared on either side of the
      anterior region and proliferated to form a pair of dorsolateral ganglia. The
      ganglia gave rise to fine varicose fibres that innervated the preoral and adoral
      ciliated bands. Peptidergic cells also innervated the postoral ciliated band, and
      a nerve tract connected the pre- and postoral bands. Fully developed bipinnaria
      had a well-developed peptidergic system, the organisation of which reflected the
      bilateral larval body plan. As the brachiolar attachment complex differentiated
      at the anterior end, the ganglia became positioned on either side of the anterior
      projection, from which they innervated the complex. It is suggested, based on the
      distribution of S1-like immunoreactivity in association with ciliary and
      attachment structures, that the peptidergic system functions in modulation of
      feeding, swimming, and settlement. The larval peptidergic system degenerates as
      the larval body is resorbed during metamorphosis. In adults, S1-like
      immunoreactivity was intense in the axonal region of the ectoneural nervous
      system and in hyponeural perikarya. Immunoreactive cells in the neuroepithelium
      connected with the surface and may be sensory. Examination of immunoreactivity in
      several Patiriella species attests to the highly conserved organisation of the
      peptidergic system in adult asteroids.

PMID- 12209831
TI  - Large-scale morphological survey of mouse retinal ganglion cells.
AB  - Five hundred twenty ganglion cells in an isolated whole-mount preparation of the
      mouse retina were labeled using the "DiOlistic" method (Gan et al. [2000] Neuron
      27:219-225) and were classified according to their morphological properties.
      Tungsten particles coated with a lipophilic dye (DiI) were propelled into the
      whole-mount retina using a gene gun. When a dye-coated particle contacted the
      cell membrane, the entire cell was labeled. The ganglion cells were classified
      into four groups based on their soma size, dendritic field size, and pattern and
      level of stratification. Broadly monostratified cells were classified into three
      groups: RG(A) cells (large soma, large dendritic field), RG(B) cells (small to
      medium-sized soma, small to medium-sized dendritic field), and RG(C) cells (small
      to medium-sized size soma, medium-sized to large dendritic field). Bistratified
      cells were classified as RG(D). This study represents the most complete
      morphological classification of mouse retinal ganglion cells available to date
      and provides a foundation for further understanding of the correlation of
      physiology and morphology and ganglion cell function with genetically manipulated
      animals.

PMID- 12209832
TI  - Mitotic activation of proliferative cells in the inner nuclear layer of the
      mature fish retina: regulatory signals and molecular markers.
AB  - New neurons continuously differentiate within the otherwise mature retina of
      teleost fish, both under normal conditions and in response to injury. We
      investigated the effects of surgical injury and intraocular injection of
      neurotrophic factors on the mitotic rate of proliferative inner nuclear layer
      cells (PINC). PINC are continually born in the inner nuclear layer and then
      migrate to the outer nuclear layer (ONL). Surgical excision of a part of a retina
      activates PINC mitotic activity near and far from the lesion. In the injured eye,
      up-regulation of PINC cells is largest in the dorsonasal sector of the retina,
      regardless of the site of lesion. Up-regulation extends even to the unlesioned
      contralateral eye, where it occurs in the same dorsonasal sector. Intraocular
      injection of ciliary neurotrophic factor mimics the effect of injury on PINC in
      the treated eye but not on the untreated contralateral retina. We searched for
      the expression in PINC of Pax6, a transcription factor linked to retinal
      progenitor cells and found that less than 0.5% of all PINC cells express it.
      Importantly, the number of Pax6-expressing PINC does not change significantly in
      the retinas subjected to any of the experimental manipulations tested. Under
      normal conditions, the default fate of PINC cells is to migrate to the ONL and,
      likely, replenish the rod progenitor pool. PINC respond to injury (both surgical
      and light-dependent) by increasing their mitotic rate; this increase is long
      lived, but there are no changes in the expression level of Pax6. PINC probably
      are a heterogenous cell population that can be specified for ultimate, different
      purposes: creating rod precursors, creating founder cells, creating cone
      precursors. Several fates are recognized now, but others may also be possible.

PMID- 12209833
TI  - N-methyl-D-aspartate receptor blockade inhibits estrogenic support of dendritic
      growth in a sexually dimorphic rat spinal nucleus.
AB  - The lumbar spinal cord of rats contains the sexually dimorphic, steroid-sensitive
      spinal nucleus of the bulbocavernosus (SNB). Dendritic development of SNB
      motoneurons requires the action of both androgens and estrogens. Estrogenic
      effects are limited to the initial growth of SNB dendrites through 4 weeks of
      age. During this postnatal period, dendritic growth in other spinal motoneurons
      is regulated by N-methyl-D-aspartate (NMDA) receptor activation. In this study,
      we tested whether NMDA receptor activation was involved in SNB dendritic growth
      and whether the estrogenic support of SNB dendritic growth was dependent on the
      activation of NMDA receptors. Motoneuron morphology was assessed in normal males,
      intact males treated daily with the NMDA receptor antagonist MK-801, castrated
      males treated with estradiol benzoate (EB), and castrated males treated with both
      EB and MK-801. SNB motoneurons were retrogradely labeled with cholera toxin
      horseradish peroxidase at 4 weeks of age (when dendritic length is normally
      maximal) and reconstructed in three dimensions. Somal area and dendritic length
      of SNB motoneurons in MK-801-treated, intact males were below those of normal
      males. Dendritic growth was partially supported in EB-treated castrates, but this
      growth was blocked by MK-801 treatment. These results suggest that, as in other
      motoneurons, dendritic development in the SNB involves NMDA receptors and,
      furthermore, that the estrogen-sensitive component of SNB dendritic development
      requires their activation.

PMID- 12209834
TI  - Role of Emx2 in the development of the reciprocal connectivity between cortex and
      thalamus.
AB  - Emx2 knockout mice appear to show a shift in the areal identity in the cerebral
      cortex , which is matched with altered distribution of thalamocortical
      projections (Bishop et al. [2000] Science 288:344-349; Mallamaci et al. [2000]
      Nat Neurosci. 3:679-686) [corrected]. We have examined the early establishment of
      these projections to understand how the altered Emx2 expression results in
      changes in their cortical targeting. We used carbocyanine dye tracing to
      visualize thalamocortical and corticofugal projections as well as
      immunohistochemistry for L1 and TAG-1, respective markers of the two axonal
      systems, in wild-type, heterozygote, and null mutant for Emx2 at embryonic (E)
      ages ranging from E13.5 to E18.5. These tracing studies demonstrated that, in
      Emx2 knockout mice, a large proportion of early thalamocortical projections were
      misrouted at the border between the diencephalon and telencephalon. This
      abnormality was associated with displaced connectivity of the internal capsule
      cells at the diencephalic-telencephalic junction. Interestingly, most of the
      aberrant thalamic projections compensated for the ventral entry to the
      telencephalon and still ascended to the cortex. Although this early targeting
      abnormality is associated with the altered Emx2 expression pattern in the cortex,
      it most probably occurs independently from it, and is related to earlier guidance
      defects at the diencephalic-telencephalic boundary. These defects might result in
      the altered and delayed arrival of thalamic projections to the cortex and, thus,
      contribute to the shifted thalamocortical matching previously observed in the
      Emx2 knockout mice.

PMID- 12209835
TI  - Anatomy of the brain neurogenic zones revisited: fractones and the
      fibroblast/macrophage network.
AB  - Cytogenesis in adult peripheral organs, and in all organs during development,
      occurs nearby basal laminae (BL) overlying connective tissue. Paradoxically,
      cytogenesis in the adult brain occurs primarily in the subependymal layer (SEL),
      a zone where no particular organization of BL and connective tissue has been
      described. We have reinvestigated the anatomy of the area considered the most
      neurogenic in the adult brain, the SEL of the lateral ventricle, in zones
      adjacent to the caudate putamen, corpus callosum, and lateral septal nucleus.
      Here, we report structural (confocal microscopy using laminin as a marker) and
      ultrastructural evidence for highly organized extravascular BL, unique to the
      SEL. The extravascular BL, termed fractones because of their fractal
      organization, were regularly arranged along the SEL and consisted of stems
      terminating in bulbs immediately underneath the ependyma. Fractones contacted
      local blood vessels by means of their stems. An individual fractone engulfed in
      its folds numerous processes of astrocytes, ependymocytes, microglial cells, and
      precursor cell types. The attachment site (base) of stems to blood vessels was
      extensively folded, overlying large perivascular macrophages that belong to a
      fibroblast/macrophage network coursing in the perivascular layer and through the
      meninges. In addition, collagen-1, which is associated with BL and growth factors
      during developmental morphogenetic inductions, was immunodetected in the SEL and
      particularly regionalized within fractones. Because macrophages and fibroblasts
      produce cytokines and growth factors that may concentrate in and exert their
      effect from the BL, we suggest that the structure described is implicated in
      adult neurogenesis, gliogenesis, and angiogenesis.

PMID- 12209836
TI  - Differential expression of calretinin and metabotropic glutamate receptor
      mGluR1alpha defines subsets of unipolar brush cells in mouse cerebellum.
AB  - The unipolar brush cell (UBC) is a type of glutamatergic interneuron in the
      granular layer of the cerebellum. The UBC brush and a single mossy fiber (MF)
      terminal contact each other within a cerebellar glomerulus, forming a giant
      synapse. Many UBCs receive input from extrinsic MFs, whereas others are
      innervated by intrinsic mossy terminals formed by the axons of other UBCs. In all
      mammalian species so far examined, the vestibulocerebellum is enriched of UBCs
      that are strongly immunoreactive for the calcium binding protein calretinin (CR)
      in both the somatodendritic and axonal compartment. UBCs have postsynaptic
      ionotropic glutamate receptors and extrasynaptic metabotropic glutamate receptors
      that immunocytochemically highlight their somatodendritic compartment and brush,
      respectively. In this study on the mouse cerebellum, we present evidence that
      immunoreactivities to CR and mGluR1alpha define two distinct UBC subsets with
      partly overlapping distributions in lobule X (the nodulus). In sections double
      labeled for CR and mGluR1alpha, the patterns of distributions of
      CR(+)/mGluR1alpha(-) UBCs and CR(-)/mGluR1alpha(+) UBCs differed along the
      mediolateral and dorsoventral axes of the folium. Moreover, mGluR1alpha(+) UBCs
      outnumbered CR(+) UBCs. Both UBC subsets were mGluR2/3, GluR2/3, and NMDAR1
      immunoreactive. The different distribution patterns of the two UBC subsets within
      lobule X suggest that expression of CR or mGluR1alpha by UBCs may be afferent
      specific and related to the terminal fields of different vestibular MF afferents.

PMID- 12209838
TI  - Changes in expression of fibroblast growth factor receptors during development of
      the mouse retinofugal pathway.
AB  - Retinal axons undergo several changes in organization as they pass through the
      region of the optic chiasm and optic tract. We used immunocytochemistry to
      examine the possible involvement of fibroblast growth factor receptors (FGFR) in
      these changes in retinal axon growth. In the retina, at all ages examined,
      prominent staining for FGFR was seen in the optic fiber layer and at the optic
      disk. At embryonic day 15 (E15), FGFR immunoreactivity was also detected in the
      ganglion cell layer, as defined by immunoreactivity for islet-1. At later
      developmental stages (E16 to postnatal day 0), FGFR were found in the optic fiber
      layer and the inner plexiform layer. In the ventral diencephalon, immunostaining
      for FGFR was first detected at E13 in a group of cells posterior to the chiasm.
      These cells appeared to match the neurons that are immunopositive for the stage
      specific embryonic antigen-1 (SSEA-1). FGFR staining was also found on the
      retinal axons at E13. At E14-E16, when most axons are growing across the chiasm
      and the tract, a dynamic pattern of FGFR immunoreactivity was observed on the
      retinal axons. The staining was reduced when axons reached the midline but was
      increased when axons reached the threshold of the optic tract. These results
      suggest that axon growth and fiber patterning in distinct regions of the
      retinofugal pathway are in part controlled by a regulated expression of FGFR.
      Furthermore, the axons with elevated FGFR expression in the optic tract have a
      posterior border of rich FGFR expression in the lateral part of the diencephalon.
      This region overlaps with a lateral extension of the SSEA-1-positive cells,
      suggesting a possible relation of these cells to the elevated expression of FGFR.

PMID- 12209839
TI  - Ultrastructure of afferents from the zona incerta to the posterior and
      parafascicular thalamic nuclei of rats.
AB  - We have examined the general ultrastructure of the posterior thalamic (Po) and
      parafascicular (Pf) nuclei of the dorsal thalamus, together with the
      ultrastructure of afferents to these nuclei from the zona incerta (ZI). The ZI of
      Sprague-Dawley rats was injected with biotinylated dextran (BD) by using
      stereotaxic coordinates, and the brains were prepared for routine BD
      histochemistry. The Po and Pf were then dissected free and processed for electron
      microscopy by using standard methods. A survey of the general ultrastructure of
      Po and Pf revealed many RS profiles (small with round vesicles) making asymmetric
      synapses around single, small (distal; 0.5-1.5 microm in diameter) or larger
      (proximal; 2-4 microm in diameter) dendrites. RL (large with round vesicles) and
      F type (pleomorphic vesicles) profiles, although sparse, were also observed.
      Single RLs were seen to envelope proximal dendrites and make asymmetric synapses
      that usually had a perforated appearance. F type profiles were seen to make
      symmetric synapses on proximal and sometimes distal dendrites. There were no
      profiles making synapses on other vesicle-filled profiles seen, reflecting the
      scarcity of interneurons in the Po and Pf of rats. Finally, BD-labeled terminal
      profiles from the ZI formed a homogeneous population within both the Po and Pf.
      They were small (1.1 +/- 0.2 microm in diameter; n = 238), contained round
      vesicles, and made asymmetric synapses with proximal ( approximately 75%) and, to
      a lesser extent, distal ( approximately 25%) dendrites; they formed part of the
      RS population of the Po and Pf. In conclusion, our results indicate that the ZI
      imparts a presumably excitatory (asymmetric synapses) input of high efficacy
      (preference for proximal dendrites) to the Po and Pf of the dorsal thalamus.

PMID- 12209837
TI  - Cell-specific expression of plasma membrane calcium ATPase isoforms in retinal
      neurons.
AB  - Ca(2+) extrusion by high-affinity plasma membrane calcium ATPases (PMCAs) is a
      principal mechanism for the clearance of Ca(2+) from the cytosol. The PMCA family
      consists of four isoforms (PMCA1-4). Little is known about the selective
      expression of these isoforms in brain tissues or about the physiological function
      conferred upon neurons by any given isoform. We investigated the cellular and
      subcellular distribution of PMCA isoforms in a mammalian retina. Mouse
      photoreceptors, cone bipolar cells and horizontal cells, which respond to light
      with a graded polarization, express isoform 1 (PMCA1) of the PMCA family. PMCA2
      is localized to rod bipolar cells, horizontal cells, amacrine cells, and ganglion
      cells, and PMCA3 is predominantly expressed in spiking neurons, including both
      amacrine and ganglion cells but is also found in horizontal cells. PMCA4 was
      found to be selectively expressed in both synaptic layers. Optical measurements
      of Ca(2+) clearance showed that PMCAs mediate Ca(2+) extrusion in both rod and
      cone bipolar cells. In addition, we found that rod bipolar cells, but not cone
      bipolar cells possess a prominent Na(+)/Ca(2+) exchange mechanism. We conclude
      that PMCA isoforms are selectively expressed in retinal neurons and that
      processes of Ca(2+) clearance are different in rod and cone bipolar cells.

PMID- 12209840
TI  - Morphological and electrophysiological characteristics of layer V neurons of the
      rat lateral entorhinal cortex.
AB  - The intrinsic electrophysiological and morphological properties of lateral
      entorhinal area (LEA) layer V neurons were investigated by sharp electrode
      intracellular recording and biocytin labeling in vitro. The morphological
      analysis revealed that layer V of the LEA contains three distinct subtypes of
      principal neurons, which were classified as pyramidal, horizontal, and
      polymorphic neurons. Pyramidal cells were the most abundant subtype (57%) and
      could be further subdivided into neurons with large, small, and star-like somas.
      Similarly to pyramidal cells, horizontal neurons (11%) had a prominent apical
      dendrite. However, their distinctive basal dendritic plexus extended primarily in
      the horizontal plane. Polymorphic neurons (32%) were characterized by a
      multipolar dendritic organization. Electrophysiological analysis of neurons in
      the three categories demonstrated a diversity of electrophysiological profiles
      within each category and no significant differences between groups. Neurons in
      the three subgroups could display instantaneous and/or time-dependent inward
      rectification and different degrees of spike frequency adaptation. None of the
      recorded cells displayed an intrinsic oscillatory bursting discharge. Many
      neurons in the three subgroups, however, displayed slow (3.5-14 Hz), sustained,
      subthreshold membrane potential oscillations. The morphological and
      electrophysiological diversity of principal neurons in the LEA parallels that
      previously reported for the medial entorhinal area and suggests that, with
      respect to the deep layers, similar information processing is performed across
      the mediolateral extent of the entorhinal cortex. Layer V of the entorhinal
      cortex may undertake very complex operations beyond acting as a relay station of
      hippocampal processed information to the neocortex.

PMID- 12209841
TI  - High-resolution three-dimensional imaging of the lateral plasma membrane of
      cochlear outer hair cells by atomic force microscopy.
AB  - The outer hair cells (OHCs) from the mammalian organ of Corti are assumed to
      enhance the sensitivity and the selectivity of the cochlea via an electromotile
      response to sound stimulation. These OHC mechanical changes feed energy back into
      the cochlea before completion of the transduction process by inner hair cells.
      OHC electromotility is thought to depend on specific transmembrane motor
      proteins. Electron microscopy has been used previously to image the OHC lateral
      plasma membrane, where voltage sensors and motors are located. A very specific
      and regular organization of membrane particles has been described, together with
      an equally specific submembraneous meshwork of cytoskeleton anchored to the
      plasma membrane. To confirm and extend these observations, we have used, for the
      first time on the OHC lateral wall, atomic force microscopy (AFM). As a result of
      an improved tapping mode technique as well as the unique ultrastructural
      organization of the OHC plasma membrane, we have obtained high-resolution three
      dimensional (3D) images of a markedly enhanced quality, allowing high-resolution
      3D imaging. Tapping-mode AFM confirmed the presence of regularly aligned
      particles (presumably transmembrane proteins) on both faces of the OHC plasma
      membrane. It also revealed the presence of markedly different membrane domains,
      smooth and undulating. The differences between these zones probably are due to
      local differences in cytoskeleton-membrane interactions. Moreover, 3D
      reconstructions allowed us to distinguish between globular and pore-like
      particles, a distinction that may be of great functional significance.

PMID- 12209842
TI  - Changes in MAP2 and tyrosinated alpha-tubulin expression in cochlear inner hair
      cells after amikacin treatment in the rat.
AB  - The expression of MAP2 (microtubule-associated protein 2) and of tyrosinated
      alpha-tubulin was investigated immunocytochemically in the cochleas of normal and
      amikacin-treated rats. For MAP2, two different antibodies were used: anti-MAP2ab,
      against the high molecular weight forms, and anti-MAP2abc, additionally against
      the embryonic form c. In the cochlea of the normal rat, the outer (OHCs) and
      inner (IHCs) hair cells were labeled for MAP2abc. The labeling was weaker in IHCs
      than in OHCs. The hair cells were rarely labeled for MAPab. Both OHCs and IHCs
      were labeled for tyrosinated alpha-tubulin. In the cochlea of the amikacin
      treated rat, aggregates of anti-MAP2abc and anti-tyrosinated alpha-tubulin
      antibodies were seen in the apical region of the IHCs as early as the end of the
      antibiotic treatment. In rats investigated during the following week, the cell
      body of most of the surviving IHCs were not labeled for MAP2abc and tyrosinated
      alpha-tubulin. Then, labeling for these two antibodies reappeared in the
      surviving IHCs, including their giant stereocilia. Fewer surviving IHCs were
      labeled for tyrosinated alpha-tubulin than for MAP2abc. The amikacin-poisoned
      IHCs were rarely labeled for MAP2ab. These results suggest that cochlear hair
      cells essentially express form c of MAP2. In the amikacin-damaged cochlea, the
      apical aggregation of MAP2c and tyrosinated alpha-tubulin within the poisoned
      IHCs could be implicated in a cell degenerative process. By contrast, the
      extinction and recovery of MAP2c and tyrosinated alpha-tubulin labeling in the
      remaining IHCs suggest the occurrence of a limited repair process. A possible
      role of MAP2 and tubulin in hair cell survival is discussed.

PMID- 12209843
TI  - Neuromodulatory complement of the pericardial organs in the embryonic lobster,
      Homarus americanus.
AB  - The pericardial organs (POs) are a pair of neurosecretory organs that surround
      the crustacean heart and release neuromodulators into the hemolymph. In adult
      crustaceans, the POs are known to contain a wide array of peptide and amine
      modulators. However, little is known about the modulatory content of POs early in
      development. We characterize the morphology and modulatory content of pericardial
      organs in the embryonic lobster, Homarus americanus. The POs are well developed
      by midway through embryonic (E50) life and contain a wide array of
      neuromodulatory substances. Immunoreactivities to orcokinin, extended FLRFamide
      peptides, tyrosine hydroxylase, proctolin, allatostatin, serotonin, Cancer
      borealis tachykinin-related peptide, cholecystokinin, and crustacean cardioactive
      peptide are present in the POs by approximately midway through embryonic life.
      There are two classes of projection patterns to the POs. Immunoreactivities to
      orcokinin, extended FLRFamide peptides, and tyrosine hydroxylase project solely
      from the subesophageal ganglion (SEG), whereas the remaining modulators project
      from the SEG as well as from the thoracic ganglia. Double-labeling experiments
      with a subset of modulators did not reveal any colocalized peptides in the POs.
      These results suggest that the POs could be a major source of neuromodulators
      early in development.

PMID- 12209844
TI  - Serotonin inputs to inspiratory laryngeal motoneurons in the rat.
AB  - Serotonergic neurons are distributed widely throughout the central nervous system
      and exert a tonic influence on a range of activities in relation to the sleep
      wake cycle. Previous morphologic and functional studies have indicated a role for
      serotonin in control of laryngeal motoneurons. In the present study, we used a
      combination of intracellular recording, dye-filling, and immunocytochemistry in
      rats to demonstrate close appositions between serotonin immunoreactive boutons
      and posterior cricoarytenoid (PCA) and cricothyroid (CT) motoneurons, both of
      which are located in the nucleus ambiguus and exhibit phasic inspiratory
      activity. PCA motoneurons received 29 +/- 5 close appositions/neuron (mean +/-
      SD, n = 6), with the close appositions distributed more frequently on the distal
      dendrites, less frequently on the proximal dendrites, and sparsely on the axons
      and somata. CT motoneurons received 56 +/- 15 (n = 6), with close appositions
      found on both the somata and dendrites, especially proximal dendrites. Close
      appositions on the axons were only seen on one CT motoneuron. These results
      demonstrate a significant serotonin input to inspiratory laryngeal motoneurons,
      which is more prominent on CT compared with PCA motoneurons, and may reflect the
      different functional role of the muscles that they innervate during the sleep
      wake cycle.

PMID- 12209845
TI  - Temporal and regional expression of NMDA receptor subunit NR3A in the mammalian
      brain.
AB  - NR3A is a developmentally regulated N-methyl-D-aspartate receptor (NMDAR) subunit
      that was previously known as NMDAR-L or chi-1. Unlike other NMDAR subunits, NR3A
      inhibits the NMDAR-associated ion channel in a novel manner, and a role in
      synaptogenesis has been suggested for this subunit. Here, we report a
      comprehensive study to delineate the temporal and anatomic expression of NR3A
      protein in the mammalian brain by using a monoclonal anti-NR3A antibody. NR3A
      protein was found to peak at postnatal day (P) 8, and to decrease gradually from
      P12 to adulthood in the rat central nervous system. Moreover, NR3A protein was
      heavily expressed in all areas of the isocortex, portions of the amygdaloid
      nuclei, and selective cell layers and nuclei of the hippocampus, thalamus,
      hypothalamus, brainstem, and spinal cord. NR3A protein was also expressed in the
      cerebellar cortex, whereas only weak signal was detected in the previous in situ
      studies by using riboprobes. At an ultrastructural level, NR3A was associated
      specifically with asymmetrical synapses and localized to postsynaptic membranes.
      This information will facilitate future research on NMDARs by providing clues to
      possible inclusion of the NR3A subunit in NMDARs in many brain regions.

PMID- 12209846
TI  - Alterations to neuronal polarity following permanent axotomy: a quantitative
      analysis of changes to MAP2a/b and GAP-43 distributions in axotomized motoneurons
      in the adult cat.
AB  - Following axotomy, morphologically unusual, distal processes (UDPs) emerge from
      motoneuron dendrites. These processes contain an axonal protein, growth
      associated protein 43 (GAP-43) but lack immunostaining for the dendritic protein
      microtubule-associated protein 2a/b (MAP2a/b). Thus, it appears that neuronal
      polarity alters following axotomy. Our goal was to describe this change in
      neuronal polarity on a more detailed and quantitative level. We asked two
      questions: Following axotomy, where in the entire neuron does the
      immunoreactivity for MAP2a/b and GAP-43 change and do these changes reflect a
      transformation of dendrite to axon or growth from terminal dendrites? Using
      intracellular labeling and immunocytochemistry, changes in MAP2a/b and GAP-43
      immunoreactivity were also found in processes with a morphology typical of
      terminal branches of intact motoneurons (called simple distal processes [SDPs]),
      as well as UDPs. Trajectories (the path from the soma to a single terminus) with
      UDPs and SDPs were longer than trajectories without these processes, and
      trajectories with UDPs were the longest. Trajectories without UDPs or SDPs were
      similar in length to trajectories from intact motoneurons. The distance from the
      soma to the point where MAP2a/b immunoreactivity became absent in trajectories
      with UDPs or SDPs was similar to the length of trajectories from intact
      motoneurons. Thus, following axotomy, two morphologically distinct types of axon
      like processes emerge from dendrites. The formation of these processes does not
      involve a transformation of the original dendrite, but rather growth at the ends
      of dendrites.

PMID- 12209847
TI  - Retinal characteristics of the ornate dragon lizard, Ctenophorus ornatus.
AB  - The retina of a diurnal insectivorous lizard, Ctenophorus ornatus (Agamidae) was
      investigated using microspectrophotometry and light and electron microscopy. A
      prominent broad yellow band was observed that extended across the mid-retina. The
      yellow coloration was found to originate from both oil droplets and diffuse
      pigmentation within cone inner segments. Microspectrophotometric analysis
      revealed yellow oil droplets with variable absorption of wavelengths below 520 nm
      and transparent oil droplets with no detectable absorptance between 350 and 750
      nm. Cones with transparent oil droplets lacked the diffuse yellow pigmentation.
      The mean wavelengths of maximum absorbance of visual pigments in the isolated
      cone outer segments were at 440, 493, and 571 nm. The retina was found to possess
      a deep convexiclivate fovea located within the yellow band, slightly
      dorsotemporal of the retinal midpoint. The topography of the retinal ganglion
      cells revealed that the fovea was contained within an area centralis.
      Photoreceptors were either single (80%) or unequal double (20%) cones. Within the
      region of the fovea, the cones were approximately 20% the diameter of those in
      the peripheral retina. Colored oil droplets and yellow pigment may increase
      visual acuity by absorbing short wavelength light scattered either by the
      atmosphere or the optical structures of the eye. The presence of a fovea
      containing slender cone photoreceptors and three visual pigments suggests that
      the lizard has high acuity and the potential for color vision.

PMID- 12209848
TI  - Comparison of hippocampal, amygdala, and perirhinal projections to the nucleus
      accumbens: combined anterograde and retrograde tracing study in the Macaque
      brain.
AB  - A combination of anterograde and retrograde tracing techniques was used to study
      the projections to the nucleus accumbens from the amygdala, the hippocampal
      formation (including the entorhinal cortex), and the perirhinal cortex in two
      species of macaque monkey. To help identify possible subregions within the
      nucleus accumbens, the distribution of calbindin was examined in two additional
      monkeys. Although this revealed evidence of "core"- and "shell"-like regions
      within the accumbens, these different regions could not consistently be related
      to cytoarchitectonic features. The rostral amygdala sent nearly equivalent
      projections to both the medial and the lateral portions of nucleus accumbens,
      whereas projections arising from the middle and caudal amygdala terminated
      preferentially in the medial division of nucleus accumbens. The basal nucleus was
      the major source of these amygdala efferents, and there was a crude topography as
      parts of the basal and accessory basal nuclei terminated in different parts of
      nucleus accumbens. The subiculum was the major source of hippocampal projections
      to the nucleus accumbens, but some hippocampal efferents also originated in the
      parasubiculum, the prosubiculum, the adjacent portion of CA1, and the uncal
      portion of CA3. These hippocampal projections, which coursed through the fornix,
      showed a rostrocaudal gradient as more arose in the rostral hippocampus.
      Hippocampal efferents terminated most densely in the medial and ventral portions
      of nucleus accumbens, along with light label in the adjacent olfactory tubercle.
      The entorhinal projections were more evenly distributed between the medial
      nucleus accumbens and the olfactory tubercle, whereas the perirhinal projections
      were primarily to the olfactory tubercle. These cortical inputs were less reliant
      on the fornix. Amygdala and subicular (hippocampal) projections overlapped most
      completely in the medial division of nucleus accumbens.

PMID- 12209849
TI  - Striate cortex in dichromatic and trichromatic marmosets: neurochemical
      compartmentalization and geniculate input.
AB  - The superficial layers of primate striate cortex (V1) contain a regular pattern
      of dense staining for cytochrome oxidase (CO) reactivity ("blobs") that receive
      direct input from the koniocellular layers of the lateral geniculate nucleus. It
      has been suggested that the blob regions are dedicated to processing color
      information. Here, the neurochemical compartmentalization of blobs and their
      input from the lateral geniculate nucleus (LGN) was measured in marmosets
      (Callithrix jacchus) identified as having either dichromatic or trichromatic
      color vision. In all animals, layer III of V1 showed a patchy distribution of CO.
      The spatial density of CO blobs (mean, 4.6 blobs/mm(2); range, 3.9-5.5), blob
      diameter, and the proportion of cortical area within blobs was not significantly
      different in dichromats and trichromats. The LGN input was studied by injecting
      retrograde tracer into V1. The koniocellular layers of the LGN contribute 11% of
      all relay cells, and form the only geniculate input to upper layer III of V1.
      Only half of all relay cells in the KC layers express calbindin. There is no
      obvious difference between dichromats and trichromats in the pattern of the
      geniculate projection to V1. It is concluded that the trichromatic phenotype is
      not associated with changes in the gross anatomy, neurochemistry, or organization
      of the geniculate afferents to the superficial layers of V1.

PMID- 12209850
TI  - Immunolocalization of PICK1 in the ascending auditory pathways of the adult rat.
AB  - Protein that interacts with C-kinase alpha (PICK1) is a PDZ domain protein that
      interacts with many binding partners in the central nervous system (CNS),
      including activated protein kinase Calpha and subunits of the AMPA subtype of
      glutamate receptor. Almost nothing is known about the anatomic distribution of
      PICK1 in the intact adult CNS. By using PICK1 antisera and peroxidase
      immunocytochemistry, we report on the distribution of PICK1 in the ascending
      pathways of the central auditory system of the adult rat. PICK1-immunoreactivity
      (ir) was observed in many component nuclei of the central auditory system,
      including the dorsal cochlear nucleus, anteroventral cochlear nucleus,
      posteroventral cochlear nucleus, some divisions of the superior olivary complex,
      inferior colliculus, medial geniculate body, and primary auditory cortex. The
      general staining pattern for PICK1-immunoreactivity was somatodendritic with
      scattered puncta in neuropil and somatodendritic regions. The distribution of
      PICK1 partially overlaps with PKCalpha and glutamate receptor subunits such as
      GluR2. These data suggest that PICK1 may function in the regulation of PKCalpha
      and GluR2 localization in components of the rat auditory system, which may be a
      fundamental mechanism of synaptic transmission and/or plasticity. J. Comp.
      Neurol.

PMID- 12209851
TI  - Age-related decreases in Nurr1 immunoreactivity in the human substantia nigra.
AB  - Nuclear receptor-related factor 1 (Nurr1), a member of the nuclear receptor
      superfamily, is associated with the induction of dopaminergic (DA) phenotypes in
      developing and mature midbrain neurons. It is well established that dopaminergic
      nigrostriatal function decreases with age. Whether age-related deficits in DA
      phenotypic markers are associated with alterations in Nurr1 expression is
      unknown. The present study found that virtually all of tyrosine hydroxylase
      immunoreactive (TH-ir) neurons within the young adult human substantia nigra were
      Nurr1-immunoreactive (Nurr1-ir) positive. Stereologic counts revealed a
      significant reduction in the number of Nurr1-ir nigral neurons in middle-aged
      (23.13%) and aged (46.33%) individuals relative to young subjects. The loss of
      Nurr1-ir neurons was associated with a similar decline in TH-ir neuron number. In
      this regard, TH-ir neuronal number was decreased in middle-aged (11.10%) and in
      aged (45.97%) subjects, and this loss of TH-ir neurons was highly correlated (r =
      0.92) with the loss of Nurr1-ir neurons. In contrast, the number of melanin
      containing nigral neuron number was generally stable across age groups,
      indicating that changes in Nurr1 and TH reflect phenotypic age-related changes
      and not frank neuronal degeneration. In support of this concept, confocal
      microscopic analyses of Nurr1-ir and TH-ir fluorescence intensity revealed
      parallel decreases in Nurr1- and TH-immunofluorescence as a function of age.
      These data demonstrate that age-related decline of DA phenotypic markers is
      associated with down-regulation of Nurr1 expression in the SN.

PMID- 12209853
TI  - Neonatal development of projections to the basolateral amygdala from prefrontal
      and thalamic structures in rat.
AB  - Recently an animal model for neurodevelopmental disorders has been developed. In
      this model the effects of an early neonatal [postnatal day 7 (Pd7)] basolateral
      amygdala lesion are compared with the effects of a lesion later in life (Pd21).
      Early amygdala damage results in enduring behavioral disturbances that become
      more manifest after puberty. These disturbances were not present in animals
      lesioned at Pd21. Accordingly it was postulated that the early damage may affect
      the neuroanatomical and neurochemical organization and functioning of other brain
      structures. To obtain information on the innervation of the amygdala during
      normal development, we used the retrograde tracer fluoro-gold. From neonatal day
      7 onward (studied until Pd19), retrogradely labeled cells were present in the
      caudal and rostral thalamus, the substantia innominata, and the prefrontal but
      not the caudal cortex. Development of the topography of the projecting cells
      differed substantially for the thalamic regions and substantia innominata vs. the
      cortical regions. In thalamic regions and substantia innominata, no changes were
      observed during the studied period (Pd7-Pd9). In the prefrontal cortex, the
      number of labeled cells increased (from Pd7 to Pd13), the topography of the
      location of the cells changed from unilateral to bilaminar (from Pd9 to Pd13),
      and the number of subareas in which the cells were present increased (from Pd7 to
      Pd13). In the caudal cortex, relatively few cells were present up to Pd15. From
      Pd17 onward, a bilaminar topography of the location of the cells was observed.
      These data provide information on the circuitry that may be involved in the
      aberrant neurodevelopment of neonatally amygdala-lesioned rats, which has been
      proposed as an animal model for neurodevelopmental psychopathological disorders.

PMID- 12209852
TI  - Pulvinar and other subcortical connections of dorsolateral visual cortex in
      monkeys.
AB  - The present study used injections of neuroanatomical tracers to determine the
      subcortical connections of the caudal and rostral subdivisions of the
      dorsolateral area (DL) and the middle temporal crescent area (MT(C)) in owl
      monkeys (Aotus trivirgatus), squirrel monkeys (Saimiri sciureus), and macaque
      monkeys (Macaca fascicularis and M. radiata). Emphasis was on connections with
      the pulvinar. Patterns of corticopulvinar connections were related to
      subdivisions of the inferior pulvinar (PI) defined by histochemical or
      immunocytochemical architecture. Connections of DL/MT(C) were with the PI
      subdivisions, PICM, PICL, and PIp; the lateral pulvinar (PL); and, more sparsely,
      the lateral portion of the medial pulvinar (PM). In squirrel monkeys, there was a
      tendency for caudal DL to have stronger connections with PICL than PICM and for
      rostral DL/MT(C) to have stronger connections with PICM than PICL. In all three
      primates, DL/MT(C) had reciprocal connections with the pulvinar and claustrum;
      received afferents from the locus coeruleus, dorsal raphe, nucleus annularis,
      central superior nucleus, pontine reticular formation, lateral geniculate
      nucleus, paracentral nucleus, central medial nucleus, lateral hypothalamus, basal
      nucleus of the amygdala, and basal nucleus of Meynert/substantia innominata; and
      sent efferents to the pons, superior colliculus, reticular nucleus, caudate, and
      putamen. Projections from DL/MT(C) to the nucleus of the optic tract were also
      observed in squirrel and owl monkeys. Similarities in the subcortical connections
      of the dorsolateral region, especially those with the pulvinar, provide further
      support for the conclusion that the DL regions are homologous in the three
      primate groups.

PMID- 12209854
TI  - Glial expression of estrogen and androgen receptors after rat brain injury.
AB  - Estrogens and androgens can protect neurons from death caused by injury to the
      central nervous system. Astrocytes and microglia are major players in events
      triggered by neural lesions. To determine whether glia are direct targets of
      estrogens or androgens after neural insults, steroid receptor expression in glial
      cells was assessed in two different lesion models. An excitotoxic injury to the
      hippocampus or a stab wound to the parietal cortex and hippocampus was performed
      in male rats, and the resultant expression of steroid receptors in glial cells
      was assessed using double-label immunohistochemistry. Both lesions induced the
      expression of estrogen receptors (ERs) and androgen receptors (ARs) in glial
      cells. ERalpha was expressed in astrocytes immunoreactive (ERalpha-ir) for glial
      fibrillary acidic protein or vimentin. AR immunoreactivity colocalized with
      microglial markers, such as Griffonia simplicifolia lectin-1 or OX-6. The time
      course of ER and AR expression in glia was studied in the stab wound model.
      ERalpha-ir astrocytes and AR-ir microglia were observed 3 days after lesion. The
      number of ERalpha-ir and AR-ir glial cells reached a maximum 7 days after lesion
      and returned to low levels by 28 days postinjury. The studies of ERbeta
      expression in glia were inconclusive; different results were obtained with
      different antibodies. In sum, these results suggest that reactive astrocytes and
      reactive microglia are a direct target for estrogens and androgens, respectively.

PMID- 12209855
TI  - Cellular and subcellular distribution of D-aspartate oxidase in human and rat
      brain.
AB  - The unusual amino acid D-aspartate is present in significant amounts in brain and
      endocrine glands and is supposed to be involved in neurotransmission and
      neurosecretion (Wolosker et al. [2000] Neuroscience 100:183-189). D-aspartate
      oxidase is the only enzyme known to metabolize D-aspartate and could regulate its
      level in different regions of the brain. We examined the cellular and subcellular
      distribution of this enzyme and its mRNA in human and rat brain by
      immunohistochemistry, in situ hybridization, and immunoelectron microscopy. D
      aspartate oxidase protein and mRNA are ubiquitous. The protein shows a granular
      pattern, particularly within neurons and to a significantly lesser extent in
      astrocytes and oligodendrocytes. No evidence for a synaptic association was
      observed. Whereas between most positive neurons only gradual differences were
      observed, in the hypothalamic paraventricular nucleus, neurons with high enzyme
      content were found next to others with no labeling. cDNA cloning of D-aspartate
      oxidase corroborates an inherent targeting signal sequence for protein import
      into peroxisomes. Immunoelectron microscopy showed that the protein is localized
      in single membrane-bound organelles, apparently peroxisomes.

PMID- 12209856
TI  - TRPC6 immunoreactivity is colocalized with neuronal nitric oxide synthase in
      extrinsic fibers innervating guinea pig intrinsic cardiac ganglia.
AB  - Tachykinins depolarize guinea pig intracardiac neurons by activating nonselective
      cationic channels. Recently, members of the transient receptor potential family
      of membrane channels (TRPC) have been implicated in the generation of G protein
      coupled receptor-activated nonselective cationic currents. We have investigated
      whether guinea pig cardiac neurons exhibit immunoreactivity to TRPC. Our results
      showed that nerve fibers within guinea pig intrinsic cardiac ganglia exhibited
      immunoreactivity to TRPC6. After culture of cardiac ganglia whole-mount explants
      for 72 hours, the TRPC6-IR fiber networks were absent. Therefore, the TRPC6-IR
      fibers were derived from sources extrinsic to the heart. A small percentage (
      approximately 3%) of intracardiac neurons also exhibited TRPC6 immunoreactivity
      in control preparations, and the percentage of cells exhibiting TRPC6
      immunoreactivity was not changed following explant culture for 72 hours. The few
      intrinsic TRPC6-IR neurons also exhibited nitric oxide synthase (NOS)
      immunoreactivity, indicating that they were nitrergic as well. We compared the
      immunohistochemical staining patterns of TRPC6-IR fibers with the staining
      patterns of a number of other neurotransmitters or neurotransmitter synthetic
      enzymes that mark specific extrinsic inputs to the intrinsic cardiac ganglia. The
      TRPC6-IR fibers were not immunoreactive for choline acetyltransferase, tyrosine
      hydroxylase, or substance P. However, the TRPC6-IR fibers exhibited
      immunoreactivity to neuronal NOS. Therefore, we propose that the TRPC6-IR fibers
      within the guinea pig intrinsic cardiac ganglia are vagal sensory fibers that
      also contain NOS. We found, in support of this conclusion, that TRPC6-IR cells
      were also present in sections of nodose ganglia.

PMID- 12209858
TI  - Introduction: The (overlooked) virtues of "unvirtuous" attitudes and behavior:
      reconsidering negativity, complaining, pessimism, and "false" hope.
AB  - The attitudes and behaviors examined in this special section-namely, negativity,
      complaining, pessimism, and "false" hope-have not typically been viewed as
      virtuous either in popular culture or in professional psychology. In
      reconsidering these attitudes and behaviors, each of the authors demonstrates how
      there may actually be virtue, or at least something positive, in what has
      typically been cast in a negative light.

PMID- 12209857
TI  - Distribution of galanin receptor 1 immunoreactivity in the rat stomach and small
      intestine.
AB  - Galanin affects gastrointestinal functions by activating different G protein
      coupled receptors. Here, we identified the sites of expression of the galanin
      receptor 1 (GAL-R1) subtype in the rat stomach and small intestine by using
      immunohistochemistry with an antibody raised to the third intracellular loop of
      rat GAL-R1 (GAL-R1(Y225-238)) and confocal microscopy. Antibody specificity was
      confirmed by (1) the detection of a band at approximately 70 kDa in Western blot
      of membranes from GAL-R1 transfected cells, (2) the cell surface staining of GAL
      R1 transfected cells, which was not detected in control cells, and (3) the
      abolition of Western signal and tissue immunostaining by preadsorbing the
      antibody with the peptide used for immunization. GAL-R1 immunoreactivity was
      localized to the cell surface of enterochromaffin-like cells, and of myenteric
      and submucous neurons, and to fibers distributed to the plexuses, interconnecting
      strands, muscle layers, vasculature, and mucosa. A dense network of GAL-R1
      immunoreactivity was observed in the deep muscular plexus in very close
      association with interstitial cells of Cajal visualized by c-kit immunostaining.
      In the ileum, 81.6% of GAL-R1 myenteric neurons and 70.7% of GAL-R1 submucosal
      neurons were substance P immunoreactive. Vasoactive intestinal polypeptide
      immunoreactivity was found in 48.3% of GAL-R1 submucosal neurons, but not in GAL
      R1 myenteric neurons. These findings support the hypothesis that GAL-R1 mediates
      galanin actions on gastrointestinal motility and secretion by modulating the
      release of other neurotransmitters and contributes to galanin-induced inhibition
      of gastric acid secretion by means of the suppression of endogenous histamine
      release.

PMID- 12209859
TI  - The tyranny of the positive attitude in America: observation and speculation.
AB  - According to both popular and professional indicators, the push for the positive
      attitude in America is on the rise. After considering the popular culture
      zeitgeist, I compare and contrast two recent professional psychology movements
      those of positive psychology and postmodern therapy-both of which rest on a
      foundation of optimism and positive thinking despite their opposing views about a
      proper philosophy of science. I then present cross-cultural empirical research
      that calls into question the typical (North American) assumption that a positive
      attitude is necessary for (a sense of) well-being. I also consider findings in
      health psychology, clinical/counseling psychology, and organizational behavioral
      science, findings which call into question the assumption that accentuating the
      positive (and eliminating the negative) is necessarily beneficial in terms of
      physical and mental health. The clinical/therapeutic implications of this
      analysis are addressed, as I put forth my conjecture about the existence of what
      I call the "tyranny of the positive attitude" in the form of a question: If there
      indeed now exists unprecedented pressure to accentuate the positive, could it
      then be that the pressure itself to be happy and optimistic contributes to at
      least some forms of unhappiness?

PMID- 12209860
TI  - The positive psychology of negative thinking.
AB  - As the positive psychology movement gains momentum, both within psychology and in
      the broader culture, it becomes increasingly important to ensure that the
      complexity of individual personality and psychological processes do not get lost
      in a "one-size-fits-all" approach to improving human functioning. In this
      article, we consider some of the ways that the costs and benefits of different
      kinds of optimism and pessimism may vary across different individuals,
      situations, and cultural contexts. We use defensive pessimism research to
      illustrate that there are times when pessimism and negative thinking are indeed
      positive psychology, as they lead to better performance and personal growth. We
      also consider the ways in which dominant American culture--and research in
      psychology--may underestimate some of the costs of optimism.

PMID- 12209861
TI  - "False" hope.
AB  - "False" hope is condemned in the literature on the grounds that it reflects the
      counterproductive use of: (a) expectations based on illusions rather than
      reality, (b) inappropriate goals, and (c) poor strategies to reach desired goals.
      Snyder, Harris, et al.'s (1991) hope theory involving self-referential thoughts
      about finding routes to desired goals (pathways) and the motivation to use those
      routes (agency) is used as a framework for examining these three criticisms of
      false hope. It is concluded that the presently available evidence does not
      support any of the false-hope criticisms. The implications of hope-related issues
      for the applied clinical arena are discussed.

PMID- 12209862
TI  - Whining, griping, and complaining: positivity in the negativity.
AB  - Recent years have seen a surge of interest in the positive psychology movement.
      The emphasis of positive psychology is on human virtue rather than on human vice,
      on human strength rather than human frailty. In an effort to focus on what is
      good about human nature, however, the positive psychology movement has neglected
      to examine the redeeming features of seemingly aversive behaviors. Thus, the
      purpose of the present article is to broaden the scope of positive psychology by
      examining, in addition to its negative facets, the positive features of one
      particular aversive behavior, complaining. After defining complaining, we address
      the personal, relational, interpersonal, and material benefits of complaining to
      show that there is, indeed, positivity in the negativity.

PMID- 12209863
TI  - Focusing on the positive, focusing on the negative: implications for
      psychotherapy.
AB  - Each of the contributions in this special section challenges some of our
      preciously held notions. We are challenged to be aware that an overfocus on
      positivity and optimism can be tyrannical, see the positivity in the negativity,
      realize that some pessimism can be adaptive, see that complaining has positive
      value, and be aware that false hope is not necessarily bad. Through an
      examination of these, I have suggested that (a) we have to be careful to deeply
      respect the individuality of our clients and to take seriously the possibility
      that there is some "ecological wisdom" in their apparently dysfunctional
      behavior, and (b) what is more important than optimism-pessimism, complaining
      versus not complaining, or false versus realistic hope is the degree to which the
      client adopts a task-focused orientation towards problems.

PMID- 12209864
TI  - Use of the reasons for depression questionnaire with adolescents.
AB  - The Reasons For Depression Questionnaire (RFD) was developed to examine the
      explanations that people give for being depressed. In its original form it was
      evaluated with samples of non-depressed and depressed university students and
      other adults. The data reported here were used to evaluate the use of the RFD
      with a community sample of New Zealand adolescents. While the underlying eight
      factor structure reported by the original authors was confirmed, with the
      addition of a ninth biological factor, additional principal component-factor
      analysis supported the existence of a six-factor solution for adolescents. The
      revised factor structure incorporated a revision of the scale's item content. It
      is proposed that an abbreviated scale (RFD-A) using 35 of the original 48 items
      would be more appropriate for use with adolescents.

PMID- 12209865
TI  - The reliability of the Massachusetts Substance Abuse Management Information
      System.
AB  - State substance abuse management information systems increasingly are becoming
      important tools for research, program management, and policy formulation at
      federal and state levels. These systems are currently undergoing radical
      expansion, leading to the creation of statewide performance and outcome
      monitoring systems for publicly-funded substance abuse treatment. This expansion
      makes imperative increased knowledge of the psychometric properties of the data
      in these systems. This study develops a method for examining the reliability of
      such data and applies it to the Massachusetts Substance Abuse Management
      Information System (SAMIS). Cohen's kappa, intraclass correlations, and the
      techniques of Heise (1969) are used to assess the reliability of different types
      of variables. Results show that key variables on the SAMIS Admission Form exhibit
      moderate to high reliability, supporting the use of this data for aggregate
      analyses. At the same time, caution should be used in making judgments about
      individual patients.

PMID- 12209867
TI  - Prediction of personality disorder traits by psychosis proneness scales in a
      German sample of young adults.
AB  - Prior research has focused on schizophrenia-spectrum disorder traits in psychosis
      prone subjects. The whole range of personality disorders were only explored in
      patient samples and with the relatives of patients. In light of this situation,
      the predictive value of Physical Anhedonia (PhA), Perceptual Aberration (PER),
      and Magical Ideation (MI) for personality disorder traits were examined
      dimensionally and categorically in a non-patient sample. We selected a non
      student sample (n = 404) and focused on two risk groups (PhA: n = 14; combined
      PER/MI: n = 36), and a control group (n = 19) using the SCID II to assess
      personality disorders at a time period two years later. MI explained most of the
      variance in clinically relevant schizotypal personality disorder symptoms, while
      PER and PhA dimensionally were associated with the number of diagnostic criteria
      met for other personality disorders. While both risk groups exceeded the control
      group in clinically relevant borderline traits, only the PER/MI-individuals
      differed in fulfilling more criteria for schizotypal personality disorder.

PMID- 12209866
TI  - Treatment of PTSD: stress inoculation training with prolonged exposure compared
      to EMDR.
AB  - The effectiveness of Stress Inoculation Training with Prolonged Exposure (SITPE)
      was compared to Eye Movement Desensitization and Reprocessing (EMDR). Twenty-four
      participants who had a diagnosis of Post Traumatic Stress Disorder (PTSD) were
      randomly assigned to one of the treatment conditions. Participants were also
      their own wait-list control. Outcome measures included self-report and observer
      rated measures of PTSD, and self-report measures of depression. On global PTSD
      measures, there were no significant differences between the treatments at the end
      of therapy. However on the subscale measures of the degree of intrusion symptoms,
      EMDR did significantly better than SITPE. At follow-up EMDR was found to lead to
      greater gains on all measures.

PMID- 12209868
TI  - The development and validation of the Dormitory Observation Report: a behavioral
      rating instrument for juvenile delinquents in residential care.
AB  - In order to provide an objective measure of problematic behavioral patterns among
      juvenile delinquents in residential facilities, the Dormitory Observation Report
      (DOR) was developed. The DOR assesses 11 dimensions of problematic behavioral
      patterns (e.g., physical assaultiveness, manipulativeness), as well as three
      dimensions of desirable behavioral patterns expected in an institutional setting
      (e.g., independent functioning, personal hygiene, care of surroundings).
      Empirical study regarding the reliability and validity of the DOR are reported,
      and the results are discussed in terms of the theoretical and practical
      implications of this instrument.

PMID- 12209869
TI  - The psychological effects of a lifestyle management course on war veterans and
      their spouses.
AB  - This research assessed the effect on a war-veteran outpatient group in a week
      long residential lifestyle-management course. This course also included the
      veterans' partners, and all participants were assessed at intake, post
      intervention, and at three- and six-month follow-ups. In summary, it was found
      that while there was a statistically significant drop in PTSD symptomatology for
      the veterans, the clinical utility of this improvement was minimal, with an
      estimated effect size of d = 0.19 by six-month follow-up. However, the veterans
      displayed a significant decrease in measures of depression, anxiety, and stress
      by six-month follow-up, all with small-to-moderate effect sizes. Likewise,
      ratings of anger showed statistically significant improvement with a moderate
      effect size. While dyadic adjustment displayed a significant improvement to six
      month follow-up, the derived effect size was small for the veterans. The spouses
      (all females in this study) displayed larger effect sizes on all measures, with
      the exception of ratings of anger, where a small effect was noted. Subjective
      quality-of-life indices displayed a significant change in the desired direction,
      although with a minimal effect for the veterans and a small effect size for the
      females. It was not feasible to have a control group during this naturalistic
      investigation and, therefore, caution is advised in over-generalizing from these
      data. However, these results warrant further 'controlled' investigation into the
      inclusion of spouses in the treatment of veterans and the utility of lifestyle
      management courses as a first step in the treatment of trauma related problems
      that have become chronic in nature within the veteran community.

PMID- 12209870
TI  - Development of a measure that integrates positive and negative affect and
      personality: the Comprehensive Personality and Affect Scales.
AB  - The development, reliability and validity of a new measure of personality and
      affect, the Comprehensive Personality and Affect Scales (COPAS) was investigated
      in three studies of college students. In study 1, the factor structure of
      personality, negative affect, and positive affect was assessed, with five-factors
      found in each of the three analyses. Fifteen scales (Personality: Emotionality,
      Extroversion, Openness, Conscientiousness, and Agreeableness; Negative Affect:
      Depression, Hostility, Agitation, Anxiety, and Social Anxiety; Positive Affect:
      Contentment, Joy, Love, Vigor, and Excitement) were constructed based on results
      of the factor analysis. Confirmatory factor analyses confirmed the measurement
      model. In study 2, the reliability and construct validity of each of the 15
      factor-derived scales was assessed in both referred and non-referred college
      students. Study 3 investigated the utility of the COPAS scales in differentiating
      referred and non-referred college students. Results indicated that reliability of
      the scales was good to excellent, while convergent and divergent validity was
      good for most scales. The COPAS scales were also shown to differentiate between
      referred and non-referred samples of college students. Overall, the COPAS was
      shown to be suitable for research with college student populations.

PMID- 12209871
TI  - Do early responders to psychotherapy maintain treatment gains?
AB  - This study examined early positive response to psychotherapy in a sample of 147
      college student clients seeking therapy at a university counseling center. Early
      response was determined based on a score representing the difference between
      client-obtained symptom distress session scores and expected scores derived from
      a large actuarial study of typical treatment response. In the present study,
      early positive response to therapy was associated with fewer psychological
      symptoms at therapy termination and follow-up and maintenance of therapy gains.
      These results are discussed in relation to placebo effects and common factors and
      their primary importance in producing meaningful change. Future research
      directions are recommended that include the use of early response for exploring
      the contribution of client variables and theoretically derived interventions as
      they relate to the outcome of psychotherapy.

PMID- 12209872
TI  - Reasons for therapy termination in a university psychology clinic.
AB  - This study examined the reasons for therapy termination documented by graduate
      student therapists. The closed case files of individual adult clients who had
      terminated their therapy experience at a university-based psychology clinic were
      reviewed. Results indicated that the most frequent reasons for termination
      documented by graduate student therapists were that clients stopped attending
      therapy sessions without providing their therapists with notice or reason and
      that clients reached a satisfactory termination point in their therapy
      experience. A substantial number of clients terminated therapy because of
      difficulties unrelated to therapy, seeking services elsewhere, or dissatisfaction
      with therapy services. Level of depressive symptomatology and the number of
      sessions attended differed across clients who had different reasons for
      termination. By addressing such client concerns early in the therapy experience,
      premature termination may be prevented.

PMID- 12209873
TI  - The Existential Loneliness Questionnaire: background, development, and
      preliminary findings.
AB  - We described the background and the development of a new measure of existential
      loneliness, the Existential Loneliness Questionnaire (ELQ). Specifically, we
      analyzed the items of the preliminary version of the ELQ (ELQ-P) using methods
      based on item response theory (the Rasch model) and examined the convergent and
      discriminative validity of the ELQ in a sample of 47 HIV-infected women. Item
      analysis produced an ELQ version consisting of 22 items that were internally
      consistent and performed well in measuring an underlying construct conceptualized
      as existential loneliness. In addition, the ELQ discriminated well between
      symptomatic and asymptomatic HIV-infected women. The ELQ correlated strongly with
      measures of depression, loneliness not identified as existential and purpose-in
      life and moderately strongly with a measure of hopelessness. Holding constant
      depression scores, the correlation between the ELQ and loneliness not identified
      as existential was significantly attenuated. Limitations of the study include the
      small sample size, which precluded an analysis of the dimensional structure of
      the ELQ.

PMID- 12209874
TI  - Calcium channel blockers inhibit galvanotaxis in human keratinocytes.
AB  - Directed migration of keratinocytes is essential for wound healing. The migration
      of human keratinocytes in vitro is strongly influenced by the presence of a
      physiological electric field and these cells migrate towards the negative pole of
      such a field (galvanotaxis). We have previously shown that the depletion of
      extracellular calcium blocks the directional migration of cultured human
      keratinocytes in an electric field (Fang et al., 1998; J Invest Dermatol 111:751
      756). Here we further investigate the role of calcium influx on the
      directionality and migration speed of keratinocytes during electric field
      exposure with the use of Ca(2+) channel blockers. A constant, physiological
      electric field strength of 100 mV/mm was imposed on the cultured cells for 1 h.
      To determine the role of calcium influx during galvanotaxis we tested the effects
      of the voltage-dependent cation channel blockers, verapamil and amiloride, as
      well as the inorganic Ca(2+) channel blockers, Ni(2+) and Gd(3+) and the Ca(2+)
      substitute, Sr(2+), on the speed and directionality of keratinocyte migration
      during galvanotaxis. Neither amiloride (10 microM) nor verapamil (10 microM) had
      any effect on the galvanotaxis response. Therefore, calcium influx through
      amiloride-sensitive channels is not required for galvanotaxis, and membrane
      depolarization via K(+) channel activity is also not required. In contrast,
      Sr(2+) (5 mM), Ni(2+) (1-5 mM), and Gd(3+) (100 microM) all significantly inhibit
      the directional migratory response to some degree. While Sr(2+) strongly inhibits
      directed migration, the cells exhibit nearly normal migration speeds. These
      findings suggest that calcium influx through Ca(2+) channels is required for
      directed migration of keratinocytes during galvanotaxis and that directional
      migration and migration speed are probably controlled by separate mechanisms.

PMID- 12209875
TI  - PTH-dependent adenylyl cyclase activation in SaOS-2 cells: passage dependent
      effects on G protein interactions.
AB  - Parathyroid hormone (PTH) sensitive adenylyl cyclase activity (ACA) in SaOS-2
      cells varies as a function of cell passage. In early passage (EP) cells (< 6),
      ACA in response to PTH and forskolin (FOR) was relatively low and equivalent,
      whereas in late passage (LP) cells (> 22), PTH exceeded FOR dependent ACA.
      Potential biochemical mechanisms for this passage dependent change in ACA were
      considered. In EP, prolonged exposure to pertussis toxin (PT) markedly enhanced
      ACA activity in response to PTH, Isoproterenol and Gpp(NH)p, whereas ACA in
      response to FOR was decreased. In contrast, the identical treatment of LP with PT
      diminished all ACA in response to PTH, Gpp(NH)p, and FOR. The dose dependent
      effects of PT on subsequent [(32)P]ADP-ribosylation of its substrates, GTPase
      activity, as well as FOR-dependent ACA, were equivalent in EP and LP. The
      relative amounts of G(alpha)i and G(alpha)s proteins, as determined both by
      Western blot, PT and cholera toxin (CT) dependent [(32)P]ADP-ribosylation, were
      quantitatively similar in EP and LP. Western blot levels of G(alpha)s and
      G(alpha)i proteins were not influenced by prior exposure to PT. Both PT and CT
      dependent [(32)P]ADP-ribosylation were dose-dependently decreased following
      exposure to PT. However, the PT-dependent decline in CT-dependent [(32)P]ADP
      ribosylation occurred with enhanced sensitivity in LP. The protein synthesis
      inhibitor cycloheximide partially reversed the PT associated decrease in FOR
      dependent ACA in EP. In contrast, cycloheximide completely reversed the PT
      associated decrease in FOR and as well as PTH dependent ACA in LP. G(alpha)s
      activity, revealed by cyc(-) reconstitution, was not altered either by cell
      passage or exposure to PT. The results suggest that the coupling between the
      components of the complex may be pivotally important in the differential
      responsiveness of early and late passage SaOS-2 cells to PTH.

PMID- 12209876
TI  - Modulation of the expression of p16INK4a and p14ARF by hnRNP A1 and A2 RNA
      binding proteins: implications for cellular senescence.
AB  - Cellular senescence is a terminal growth phase characteristic of normal human
      diploid fibroblasts. Altered gene expression during cellular senescence is
      numerous compared to that of younger proliferative cells in culture. We have
      previously reported that the levels and activities of hnRNP A1 and A2 RNA binding
      proteins are decreased in senescent human fibroblasts. Both proteins are
      multifunctional and may influence the expression of mRNA isoforms during
      development. In this study, we tested whether overexpression of either protein
      could modulate the mRNA isoforms of the INK4a locus, specifically p14(ARF) and
      p16(INK4a). Both INK4a mRNA isoforms have been shown to be growth suppressors and
      deletions of this locus allow cells to escape cellular senescence. We have found
      that increasing the ratio of either hnRNP A1 or A2 over that of splicing factor
      SF2/ASF results in the preferential generation of the p14(ARF) isoform.
      Overexpression of A1 or A2 RNA binding proteins also appear to increase the
      steady state mRNA levels of both isoforms, suggesting that in addition to
      alternative splicing, A1 and A2 may effect p14(ARF) and p16(INK4a) mRNA
      stability. A constitutive decrease in the ratio of hnRNP A1 or A2 to SF2/ASF in
      senescent fibroblasts is typically accompanied by an increase in the level of
      p16(INK4a) isoform. Our studies suggest that hnRNP A1 and A2 may exert an
      important role during replicative senescence by altering expression of cell cycle
      regulatory proteins through mRNA metabolism.

PMID- 12209877
TI  - Growth arrest in G1 protects against oxygen-induced DNA damage and cell death.
AB  - Although oxygen is required for normal aerobic respiration, hyperoxia (95%
      O(2)/5% CO(2)) damages DNA, inhibits proliferation in G1, S and G2 phases of the
      cell cycle, and induces necrosis. The current study examines whether growth
      arrest in G1 protects pulmonary epithelial cells from oxidative DNA damage and
      cell death. Mv1Lu pulmonary adenocarcinoma cells were chosen for studies because
      hyperoxia inhibits their proliferation in S and G2 phase, while they can be
      induced to arrest in G1 by altering culture conditions. Hyperoxia inhibited
      proliferation, increased intracellular redox, and rapidly reduced clonogenic
      survival. In contrast, Mv1Lu cells treated with transforming growth factor (TGF)
      beta1, deprived of serum or grown to confluency, arrested and remained
      predominantly in G1 even during exposure. Growth arrest in G1 significantly
      enhanced clonogenic survival by 10-50-fold. Enhanced survival was not due to
      reduction in the intracellular redox-state of the cells, but instead was
      associated with reduced DNA strand breaks and p53 expression. Our findings
      suggest that the protective effects of G1 is mediated not simply by a reduction
      in intracellular ROS, but rather through an enhanced ability to limit or rapidly
      recognize and repair damaged DNA.

PMID- 12209878
TI  - Synergistic effect of the anti-HER-2/neu antibody and cisplatin in immortalized
      and primary mesothelioma cell lines.
AB  - Malignant mesothelioma (MM) still remains a therapeutic and diagnostic problem to
      which new therapeutic perspectives are being continuously tried and tested. Three
      different primary cultures (MMGe-1, MES MM 98, and MES 1) and one immortalized
      cell line (MSTO 211 H) of human MM were studied in order to evaluate the HER
      2/neu expression. Three out of four cell lines showed a different level of c-erbB
      2 expression, the highest being detected on the MSTO 211 H cell line
      (fibroblastic phenotype), whereas MMGe-1 resulted negative. The effect of the
      anti-HER-2/neu antibody (Trastuzumab) alone, and in combination with cisplatin
      (CDDP) at different doses (ranging from 0.1 to 100 microg/ml), was studied on all
      the c-erB-2 positive cell lines. Trastuzumab was able to inhibit cell
      proliferation in a time-dependent manner, with growth inhibition also obtained at
      low concentrations (0.1-1 microg/ml). Combined treatment with Trastuzumab (10
      microg/ml) and CDDP (1 microg/ml) showed synergism. Our results were encouraging,
      and suggest a rationale for further investigations in a clinical setting.

PMID- 12209879
TI  - Proliferation of IL-6-independent multiple myeloma does not require the activity
      of extracellular signal-regulated kinases (ERK1/2).
AB  - The evolutionarily conserved Ras/Raf/MEK/ERK pathway is thought to be essential
      for proliferation of eukaryotic cells. The human multiple myeloma (MM) cell line
      8226 encodes an activated K-ras allele and proliferates without requirement for
      the main MM growth and survival factor IL-6. Surprisingly, the addition of the
      MEK1/2 inhibitors PD98059 or U0126 to 8226 cultures at doses that block virtually
      all ERK1/2 activity had minimal effects on the rapid proliferation of this cell
      line. In contrast, proliferation of the IL-6-dependent MM cell line, ANBL-6 was
      blocked by PD98059. Levels of activated forms of the other classical MAP kinases
      (JNK and p38) were very low during MM cell proliferation and, therefore, do not
      substitute for the mitogenic activities normally regulated by ERK kinases. These
      data demonstrate that proliferation of 8226 cells does not require ERK1/2
      activity, and suggest that IL-6-independent growth of MM may correlate with
      independence from a requirement for ERK activity. Other signal transduction
      pathways that appear to regulate cell cycle progression in these cells were
      examined.

PMID- 12209880
TI  - Calcium induces differentiation of primary human salivary acinar cells.
AB  - Cultivation of human parotid glands in serum-free medium (Ca(2+) concentration,
      0.2 mM) with growth supplements resulted in isolation of a homogeneous population
      of epithelial cells without any mesenchymal cells. The isolated cells showed an
      undifferentiated phenotype with scant cytoplasmic organelles, and low levels of
      alpha-amylase expression. The cells remained viable and undifferentiated for up
      to 24 passages when subcultured at 80% confluence in 0.2 mM Ca(2+) medium with a
      1:3 split ratios. There was little cell-cell contact. A Ca(2+) switch from 0.2 to
      1 mM induced cell-cell contact with translocation of desmosomal proteins from the
      cytoplasm to the cell membrane, and sequential differentiation of serous acinar
      cells with a glandular arrangement, well-developed cytoplasmic organelles and an
      increased level of alpha-amylase expression. These morphological changes and
      desmosome assembly were blocked by treatment with non-specific PKC inhibitor.
      Moreover, the addition of PKC activator, tetradecanoylphorbol 13-acetate (TPA),
      to 0.2 mM Ca(2+) medium caused transient assembly of desmosome-like structure,
      but did not induce cell-cell contact or morphological differentiation.
      Cultivation of the cells in 1.5 mM Ca(2+) medium resulted in increased
      stratification of the cells and reduced alpha-amylase expression. These findings
      provide the first demonstration that continuous cultivation in 1.0 mM Ca(2+)
      medium is required for cellular differentiation of salivary gland acinar cells,
      and maintenance of the differentiated state.

PMID- 12209881
TI  - Overexpression of the 18 kDa and 22/24 kDa FGF-2 isoforms results in differential
      drug resistance and amplification potential.
AB  - We investigated the role of low molecular weight (LMW) and high molecular weight
      (HMW) isoforms of basic fibroblast growth factor 2 (FGF-2) in the expression of
      transformation-related phenotypic alterations, drug sensitivity modulation, and
      gene amplification potential. For this purpose, we used NIH 3T3 and A31 cells
      transfected with different cDNA FGF-2 constructs allowing expression of the
      different proteins. Both cell lines showed marked phenotypic alterations when
      expressing the LMW FGF-2 or the four HMW FGF-2 isoforms: they acquired a
      transformed morphology, grew at higher saturation densities in 10% serum, and
      exhibited anchorage-independent growth and increased invasive potential. However,
      HMW FGF-2-expressing cells also grew in 1% serum and their invasive potential was
      lower than in cells expressing all FGF-2 forms or LMW FGF-2 alone. We have grown
      the different cell lines under a selective pressure of N-(phosphonacetyl)-l
      aspartate (PALA), a drug which specifically inhibits the aspartate
      transcarbamylase activity of the multifunctional carbamyl-P-synthetase/aspartate
      transcarbamylase/dihydro-orotase genes (CAD) enzyme (and thus inhibits de novo
      pyrimidine biosynthesis) and selects for cells with amplified copies of the CAD
      gene. Our results demonstrate that aberrant expression of the LMW FGF-2 and/or
      HMW FGF-2 isoforms differently modulates drug resistance and gene amplification
      properties in the NIH 3T3 and A31 cell lines by differential amplification of the
      CAD gene. Coexpression of all isoforms appears to be necessary to obtain
      cumulative effects and nuclear-targeted HMW FGF-2 has a pivotal role in such a
      cooperation.

PMID- 12209882
TI  - Sortilin is upregulated during osteoblastic differentiation of mesenchymal stem
      cells and promotes extracellular matrix mineralization.
AB  - Osteoblasts and adipocytes are derived from a common precursor in bone marrow,
      the mesenchymal stem cell (MSC). Factors driving human MSCs (hMSCs) to
      differentiate down the two lineages play important roles in determining bone
      density because it has been shown that bone volume loss associated with
      osteoporosis and aging is accompanied by reduced osteoblastic bone formation and
      increased marrow adipose tissue. The genes upregulated in hMSCs during osteogenic
      differentiation were screened using cDNA microarrays and were semi-quantitated by
      real-time RT-PCR. One of the genes identified was sortilin, which was upregulated
      one day after osteogenic induction and remained upregulated for a week. The
      overexpression of sortilin in hMSCs using an adenovirus vector resulted in the
      acceleration of mineralization during osteogenic differentiation without
      affecting alkaline phosphatase activity. Lipoprotein lipase (LPL), produced by
      adipocytes, is bound by sortilin, which may mediate its endocytosis. By adding
      LPL to osteogenic induction medium, osteoblastic mineralization was inhibited in
      a dose-dependent manner. Interestingly, sortilin overexpression abolished the LPL
      mediated suppression of osteogenic differentiation. hMSCs exist in marrow where
      LPL-producing adipose cells are abundant and where osteogenesis is negatively
      regulated by LPL. Sortilin has a counter effect of promoting osteogenesis by
      acting as a scavenger of LPL.

PMID- 12209883
TI  - Matrix protein glycation impairs agonist-induced intracellular Ca2+ signaling in
      endothelial cells.
AB  - Studies have shown diabetes to be associated with alterations in composition of
      extracellular matrix and that such proteins modulate signal transduction. The
      present studies examined if non-enzymatic glycation of fibronectin or a mixed
      matrix preparation (EHS) alters endothelial cell Ca(2+) signaling following
      agonist stimulation. Endothelial cells were cultured from bovine aorta and rat
      heart. To glycate proteins, fibronectin (10 microg/ml), or EHS (2.5 mg/ml) were
      incubated (37 degrees C, 30 days) with 0.5 M glucose-6-phosphate. Matrix proteins
      were coated onto cover slips after which cells (10(5) cells/ml) were plated and
      allowed to adhere for 16 h. For measurement of intracellular Ca(2+), cells were
      loaded with fura 2 (2 microM) and fluorescence intensity monitored. Bovine cells
      on glycated EHS showed decreased ability for either ATP (10(-6) M) or bradykinin
      (10(-7) M) to increase Ca(2+) (i). In contrast, glycated fibronectin did not
      impair agonist-induced increases in Ca(2+) (i). In the absence of extracellular
      Ca(2+), ATP elicited a transient increase in Ca(2+) (i) consistent with
      intracellular release. Re-addition of Ca(2+) resulted in a secondary rise in
      Ca(2+) (i) indicative of store depletion-mediated Ca(2+) entry. Both phases of
      Ca(2+) mobilization were reduced in cells on glycated mixed matrix; however, as
      the ratio of the two components was similar in all cells, glycation appeared to
      selectively impair Ca(2+) release from intracellular stores. Thapsigargin
      treatment demonstrated an impaired ability of cells on glycated EHS to increase
      cytoplasmic Ca(2+) consistent with decreased endoplasmic reticulum Ca(2+) stores.
      Further support for Ca(2+) mobilization was provided by increased baseline IP(3)
      levels in cells plated on glycated EHS. Impaired ATP-induced Ca(2+) release could
      be induced by treating native EHS with laminin antibody or exposing cells to
      H(2)O(2) (20-200 microM). Glycated EHS impaired Ca(2+) signaling was attenuated
      by treatment with aminoguanidine or the antioxidant alpha-lipoic acid. The
      results demonstrate that matrix glycation impairs agonist-induced Ca(2+) (i)
      increases which may impact on regulatory functions of the endothelium and
      implicate possible involvement of oxidative stress.

PMID- 12209884
TI  - Flavanones structure-related inhibition on TPA-induced tumor promotion through
      suppression of extracellular signal-regulated protein kinases: involvement of
      prostaglandin E2 in anti-promotive process.
AB  - Biological functions of flavanones have been studied extensively, however, the
      structure-related activities of flavanones on 12-o-tetradecanoylphorbol 13
      acetate (TPA)-induced promotive effects are still unclear. In this study,
      flavanone, 2'-OH flavanone, 4'-OH flavanone, 6-OH flavanone showed the most
      significant dose-dependent inhibition on TPA-induced proliferative effects among
      eight tested flavanones in NIH3T3 cells. TPA-induced mitogen activated protein
      kinases (MAPK) phosphorylation, ornithine decarboxylase (ODC), c-Jun, and
      cyclooxygenase 2 (COX-2) protein expressions in a time-dependent manner, and the
      maximal inductive time point is at 1 h for MAPK phosphorylation and 6 h for
      others. Flavanone, 2'-OH flavanone, 4'-OH flavanone, 6-OH flavanone showed the
      dose-dependent inhibition on TPA-stimulated MAPK phosphorylation, COX-2, ODC, c
      Jun protein expressions. Induction of, prostaglandin E(2) (PGE(2)) production was
      detected in TPA-treated NIH3T3 cells, and flavanone, 2'-OH flavanone, 4'-OH
      flavanone, 6-OH flavanone inhibited significantly PGE(2) production induced by
      TPA. Addition of PGE(2) reverses the inhibitory activities of flavanone, 2'-OH
      flavanone, 4'-OH flavanone, 6-OH flavanone on TPA-induced proliferation. And,
      PD98059, a specific inhibitor of ERKs, inhibited TPA-induced MAPK
      phosphorylation, accompanied by decreasing COX-2, c-Jun, and ODC protein
      expression, and showed dose-dependent inhibition on TPA-induced proliferation in
      cells. These results demonstrated that PGE(2) is an important mediator in TPA
      induced proliferation, and MAPK phosphorylation was located at the upstream of
      COX-2, c-Jun, and ODC gene expressions in TPA-induced responses. Furthermore,
      flavanone, 2'-OH flavanone, 4'-OH flavanone, 6-OH flavanone (100 microM)
      suppressed TPA-induced colony formation associated with blocking MAPK
      phosphorylation, ODC, c-Jun, and COX-2 proteins expression. And, 1,1-diphenyl-2
      picrylhydrazyl (DPPH) assay showed that flavanone, 2'-OH flavanone, 4'-OH
      flavanone, 6-OH flavanone did not perform potent anti-radical activities among
      these eight tested compounds. In conclusion, this study provided molecular
      evidences to demonstrate that flavanone, 2'-OH flavanone, 4'-OH flavanone, 6-OH
      flavanone were potent inhibitors on TPA-induced responses without notable
      cytotoxicity through suppression of PGE(2) production; and anti-radical activity
      of flavanones was not correlated with preventing the occurrence of tumor
      promotion. We proposed that blocking TPA-induced intracellular signaling
      responses might be involved in the anti-promotive mechanism of flavanones.

PMID- 12209885
TI  - Atrial natriuretic factor inhibits mitogen-induced growth in aortic smooth muscle
      cells.
AB  - Atrial natriuretic factor (ANF) is a polypeptide able to affect cardiovascular
      homeostasis exhibiting diuretic, natriuretic, and vasorelaxant activities. ANF
      shows antimitogenic effects in different cell types acting through R(2) receptor.
      Excessive proliferation of smooth muscle cells is a common phenomenon in diseases
      such as atherosclerosis, but the role of growth factors in the mechanism which
      modulate this process has yet to be clarified. The potential antimitogenic role
      of ANF on the cell growth induced by growth factors appears very intriguing. Aim
      of the present study was to investigate the possible involvement of ANF on rat
      aortic smooth muscle (RASM) cells proliferation induced by known mitogens and the
      mechanism involved. Our data show that ANF, at physiological concentration range,
      inhibits RASM cell proliferation induced by known mitogens such as PDGF and
      insulin, and the effect seems to be elicited through the modulation of
      phosphatidic acid (PA) production and MAP kinases involvement.

PMID- 12209886
TI  - Regulatory volume decrease is actively modulated during the cell cycle.
AB  - Nasopharyngeal carcinoma cells, CNE-2Z, when swollen by 47% hypotonic solution,
      exhibited a regulatory volume decrease (RVD). The RVD was inhibited by
      extracellular applications of the chloride channel blockers tamoxifen (30 microM;
      61% inhibition), 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, 100 microM;
      60% inhibition), and ATP (10 mM; 91% inhibition). The level and time constant of
      RVD varied greatly between cells. Most cells conducted an incomplete RVD, but a
      few had the ability to recover their volume completely. There was no obvious
      correlation between cell volume and RVD capacity. Flow cytometric analysis showed
      that highly synchronous cells were obtained by the mitotic shake-off technique
      and that the cells progressed through the cell cycle synchronously when incubated
      in culture medium. Combined application of DNA synthesis inhibitors, thymidine
      and hydroxyurea arrested cells at the G1/S boundary and 87% of the cells reached
      S phase 4 h after being released. RVD capacity changed significantly during the
      cell cycle progression in cells synchronized by shake-off technique. RVD capacity
      being at its highest in G1 phase and lowest in S phase. The RVD capacity in G1
      (shake-off cells sampled after 4 h of incubation), S (obtained by chemical
      arrest), and M cells (selected under microscope) was 73, 33, and 58%,
      respectively, and the time constants were 435, 769, and 2,000 sec, respectively.
      We conclude that RVD capacity is actively modulated in the cell cycle and RVD may
      play an important role in cell cycle progress.

PMID- 12209887
TI  - Titin-cap associates with, and regulates secretion of, Myostatin.
AB  - Myostatin, a secreted growth factor, is a key negative regulator of skeletal
      muscle growth. To identify modifiers of Myostatin function, we screened for
      Myostatin interacting proteins. Using a yeast two-hybrid screen, we identified
      Titin-cap (T-cap) protein as interacting with Myostatin. T-cap is a sarcomeric
      protein that binds to the N-terminal domain of Titin and is a substrate of the
      titin kinase. Mammalian two-hybrid studies, in vitro binding assays and protein
      truncations in the yeast two-hybrid system verified the specific interaction
      between processed mature Myostatin and full-length T-cap. Analysis of protein
      protein interaction using surface plasmon resonance (Biacore, Uppsala, Sweden)
      kinetics revealed a high affinity between Myostatin and T-cap with a KD of 40 nM.
      When T-cap was stably overexpressed in C(2)C(12) myoblasts, the rate of cell
      proliferation was significantly increased. Western analyses showed that
      production and processing of Myostatin were not altered in cells overexpressing T
      cap, but an increase in the retention of mature Myostatin indicated that T-cap
      may block Myostatin secretion. Bioassay for Myostatin confirmed that conditioned
      media from myoblasts overexpressing T-cap contained lower levels of Myostatin.
      Given that Myostatin negatively regulates myoblast proliferation, the increase in
      proliferation observed in myoblasts overexpressing T-cap could thus be due to
      reduced Myostatin secretion. These results suggest that T-cap, by interacting
      with Myostatin, controls Myostatin secretion in myogenic precursor cells without
      affecting the processing step of precursor Myostatin.

PMID- 12209888
TI  - Key issues involved with the use of miniature specimens in the characterization
      of the mechanical behavior of polymeric biomaterials--a review.
AB  - This article is arranged in three parts. In the first, a brief history of the use
      of miniature specimens for characterizing the mechanical behavior of materials in
      general is given. In the second part, several trends in literature reports of
      small punch and small shear punch tests of ultra-high-molecular-weight
      polyethylene and acrylic bone cement specimens are examined critically. In this
      exercise, special attention is paid to one test metric; namely, the work to
      failure [which is the area under the punch load (P) versus punch displacement
      (Delta) plot up to the failure point]. In the third part of the article, seven
      key issues in this field are discussed. In each case, the gaps in the current
      knowledge base are pointed out. Among those issues are determination of
      sensitivity of test results to test variables, development of methods for
      converting P-Delta results to bulk material properties, and constitutive modeling
      of the mechanical behavior of a polymeric biomaterial, under both small punch and
      small shear punch loading.

PMID- 12209889
TI  - Ion release in patients with metal-on-metal hip bearings in total joint
      replacement: a comparison with metal-on-polyethylene bearings.
AB  - Polyethylene (PE) wear has been shown to be a problem in long-term joint
      replacement using metal-on-PE bearing. The use of metallic heads articulating
      with metallic cups could solve this problem: success will be enhanced if wear and
      corrosion of the articulating surfaces are maintained at a low level. New models
      with metal-on-metal bearing have been proposed, to be used mainly for young
      subjects: such coupling seems to have a reduced release, but it is unclear yet if
      the medium-term corrosion rate is really negligible or, on the contrary, it is
      significantly higher than in the metal-on-PE bearing. Aim of our study was the
      comparison of ion release in the serum of two groups of patients who had the same
      type of stable cementless prosthesis, but different bearing: twenty-six patients
      with metal-on-metal (Group A) and fifteen patients with metal-on-PE bearing
      (Group B) were examined. The follow-up was 14-38 months for group A and 18-34
      months for group B. The serum concentration of chromium (Cr), cobalt (Co) and
      molybdenum (Mo) was measured. Twenty-two patients before surgery were used for
      comparison (Group C). The reference values were obtained from a population of
      twenty-two healthy subjects (Group D). Our findings indicate that metal-on-metal
      bearings produce a significantly higher systemic release of cobalt and chromium
      (ng/ml) when compared with levels found in metal-on-PE, pre-surgery and reference
      groups. Such a high release should induce to improve the bearing materials or, at
      least, to study the biologic fate of metal ions and consequently their long-term
      effects. In such a way a risk-to-benefit ratio for the patient could be
      established.

PMID- 12209890
TI  - Standardized analysis of UHMWPE wear particles from failed total joint
      arthroplasties.
AB  - Periprosthetic tissue obtained at revision surgery from eight total hip
      replacement cases was hydrolyzed, and polyethylene debris particles were isolated
      from each case. Individual particles were analyzed by scanning electron
      microscopy (SEM) and computerized image analysis in accordance with ASTM F1877
      98, a standard for quantitative description of wear debris. For comparison,
      periprosthetic tissues from eight total knee revision and four total shoulder
      revision cases were processed and analyzed with identical methods. A total of
      2599 hip, 4345 knee, and 1200 shoulder particles were analyzed. The morphologies
      of the isolated polyethylene particles from the total hip specimens were
      distinctly different from the total knee and total shoulder particles. The mean
      equivalent circle diameter (ECD) for hip particles was 0.694 microm +/- 0.005;
      knee particles measured 1.190 microm +/-0.009; and shoulder particles 1.183
      microm +/- 0.017. The ECD was significantly different between hip particles and
      those from the shoulder and knee. The mean aspect ratio (AR) for the hip
      particles was 1.626 +/- 0.015, compared to the knee particles at 1.935 +/- 0.015
      and shoulder particles at 2.082 +/- 0.033. The AR was statistically different
      among all three groups. Other descriptors from the ASTM standard, elongation (E),
      form factor (FF), and roundness (R) were all significantly different among the
      three groups of joints. This study demonstrates the utility of ASTM F1877-98 in
      differentiating wear debris particles from different sources.

PMID- 12209891
TI  - An investigation of the cytotoxicity and histocompatibility of in situ forming
      lactic acid based orthopedic biomaterials.
AB  - The cytotoxicity and biocompatibility of polymer networks prefabricated from
      multifunctional lactic acid based oligomers that are being developed for
      orthopedic applications were assessed through in vitro cytotoxicity analysis and
      subcutaneous implantation. After 7 and 14 days, no significant difference was
      observed in the relative viability or alkaline phosphatase activity of primary
      rat calvarial osteoblasts cultured in the presence or absence of degrading
      polymer networks, indicating that the degradation products had no detrimental
      effect on the function or activity of the cultured cells. The tissue response to
      preformed lactic acid networks implanted in rats consisted of a mild inflammatory
      response with an increase in fibrous capsule thickness and inflammation
      correlating with faster degrading polymer compositions. This relatively neutral
      response is indicative of a biocompatible, degradable polymer that has potential
      medical applications. Finally, porous scaffolds were implanted subcutaneously in
      rats, and vascularized fibrous tissue infiltration was highly dependent on the
      scaffold porosity and architecture. This finding indicates that an in situ
      forming porous scaffold of this composition may support the infiltration of
      surrounding vascularized tissue, and thus be applicable to orthopedic treatments
      of large bone defects.

PMID- 12209892
TI  - Deconvolution of surface topology for quantification of initial wear in highly
      cross-linked acetabular components for THA.
AB  - Evaluation of the surface morphology of short-term retrieved cross-linked
      acetabular components requires differentiation between the features generated
      during machining and the smaller-scale morphologies generated during the in vivo
      wear process. Previously, the distinction between the waviness of machining and
      the roughness of wear has been related to the grain size of the UHMWPE. Here a
      low-frequency cutoff is proposed, based on the maximum spectral frequency of
      machining marks, rather than on the grain size of the bulk UHMWPE material, as a
      reliable method for deconvolving machining marks from in vivo wear following
      short-term implantation. To this end, as-machined articulating surfaces of
      conventional (GUR 1050) and two groups of highly cross-linked UHMWPE acetabular
      components were examined to determine whether they exhibited a periodic surface
      morphology with a well-defined spatial frequency. The surface frequency spectra
      revealed low-frequency peaks associated with the machining marks, which were
      unique to each type of implant. Furthermore, the surface frequency spectra
      appeared uniform within a single group of implants. Statistically significant
      differences in the surface roughness and waviness were observed between the three
      groups of new implants. Our research suggests that machining marks can be
      effectively deconvolved from the articulating surface with the use of a Fourier
      transform algorithm with a single cutoff frequency of 0.08 1/microm,
      corresponding to a wavelength of 12.5 microm. The results of this study provide a
      unified conceptual framework for discriminating between waviness and roughness of
      the articulating surface for machined orthopedic components. The distinction
      between waviness and roughness is expected to be crucial for the comprehensive
      evaluation of wear surfaces after short-term implantation, when machining marks
      may be partially worn away or plastically deformed in vivo.

PMID- 12209893
TI  - Long-term biocompatibility of implanted polymer-based intrafascicular electrodes.
AB  - Polymer-based longitudinal intrafascicular electrodes (polyLIFEs) were
      chronically implanted into the sciatic nerve of white New Zealand rabbits (n=8)
      for a period of 6 months (hereafter referred to as the long-term group). The
      impact of the implantation procedure, as observed 6 months post surgery, was
      evaluated in a sham-treated control group (n=9). The contralateral sciatic nerve
      served as the control for each animal. Nerve-fiber counts, fiber diameters, and
      myelin thickness were estimated at the level of the implant site, 1.5 cm
      proximally, and 1.5 cm distally for both nerves in sham-treated and long-term
      groups. Implantation of polyLIFEs had no significant effect on fiber counts,
      nerve-fiber diameter, or myelin thickness. A slight increase in connective tissue
      in the vicinity of the implant site was evident in the long-term group, including
      a thin but dense capsule immediately surrounding the implanted electrode.

PMID- 12209894
TI  - Implantation study of a novel hydroxyapatite/collagen (HAp/col) composite into
      weight-bearing sites of dogs.
AB  - A hydroxyapatite/type I collagen (HAp/Col) composite, aligning hydroxyapatite
      nanocrystals along collagen molecules, has been prepared. The biocompatibility,
      osteoconductive activity, and efficacy as a carrier of rhBMP-2 of this novel
      biomaterial implanted in the weight-bearing site have been examined. The HAp/Col
      implants (15 mm in diameter and 20 mm in length) with a surface cross-linked
      layer containing rhBMP-2 (0 or 400 microg/ml) were implanted into bone defects of
      tibiae in three beagle dogs and fixed according to the Ilizarov method. As a
      control, bone defects of 20 mm in two beagle dogs did not receive implants, and
      the dogs were allowed to walk using an Ilizarov extraskeletal fixator. The
      specimens were removed from one dog in each group after 12 weeks. Also, the
      Ilizarov fixators in the rhBMP-treated dogs were removed after 12 weeks, after
      which full weight bearing started. The specimens were further taken out after 18
      and 24 weeks in the rhBMP-treated and non-rhBMP-treated dogs, and after 24 weeks
      in the control group. The change of bone mineral density, as well as radiological
      and histological findings, suggest that the implants are able to induce bone
      remodeling units and are a superior carrier of rhBMP-2 due to the stimulation of
      early callus and new bone formation.

PMID- 12209895
TI  - Characteristics and porcelain bond strength of (Ti,Al)N coating on dental alloys.
AB  - The effect of a novel titanium-aluminum nitride film, or (Ti,Al)N film, on the
      bond strength between a dental porcelain and two nickel-based dental alloy
      substrates was investigated. A thin layer of (Ti,Al)N film was deposited on flat
      metal samples using a reactive radio-frequency sputtering method. A uniform
      thickness of porcelain was applied to the film- coated metal samples. Metal
      ceramic specimens were subjected to three-point bending, and failure loads were
      recorded. Bond strengths between the porcelain and (Ti,Al)N-coated metal alloys
      ranged from 159.0 +/- 11.7 N to 278.0 +/- 12.3 N. These values were significantly
      greater (p< 0.05) than bond strengths recorded for control samples that did not
      incorporate the (Ti,Al)N film. An electron probe microanalyzer with a line
      profile mode was used to characterize the interface between the (Ti,Al)N film and
      the porcelain. Results of this investigation suggest that the (Ti,Al)N film (1)
      increases the flexural bond strength between dental porcelain and nickel-based
      alloy substrates by permitting elemental diffusion, (2) interferes with the
      surface oxide formation that characteristically originates from the nickel-based
      metal alloy substrate, and (3) provides an appropriate oxide layer for porcelain
      application.

PMID- 12209896
TI  - Effect of water treatment on the apatite-forming ability of NaOH-treated titanium
      metal.
AB  - NaOH and heat treatments of titanium metal induce an apatite-forming ability on
      the metal by producing a bioactive graded sodium titanate structure on its
      surface. An enhancement of the apatite-forming ability of titanium metal induced
      by the NaOH treatment was attempted by conjoining the water and heat treatments.
      These treatments are assumed to convert the sodium titanate into anatase, which
      is presumed to be more effective for apatite nucleation. The sodium titanate gel
      on the metal formed from the NaOH treatment was shown to transform into anatase
      by a simple immersion in pure water, with subsequent heat treatments. Forming
      anatase on the metal significantly improved the apatite-forming ability of the
      metal in a simulated body fluid (SBF). The apatite-forming ability correlated
      directly with the amount of anatase on the metal. It is therefore expected that
      bioactive titanium metal and its alloys with a higher bone-bonding ability can be
      obtained with the use of the water and subsequent heat treatments after the NaOH
      treatment.

PMID- 12209897
TI  - Comparison of two methods to measure permeability of dentin.
AB  - Dentin permeability was measured alternatively with two methods: a 10-microl
      capillary method with visual evaluation (PC) and a motorized automatic measuring
      device (Flodec, FD), both interposed in a simulated perfusion system. Eight human
      third molar coronal fragments were connected to systems, and their permeability
      to distilled water measured at 0, 5, 10, 15, 20, 25, and 29 cm H(2)O pressure.
      Resultant permeabilities (in microl/s) for both techniques were interrelated with
      the use of the Passing and Bablok nonparametric method, which gives information
      about the range of constant and proportional errors and their 95% confidence
      intervals (95CI). The relationship between the methods is described by the
      regression formula: FD = -0.0003 + 0.945.PC, with 95CI for constant (-0.0015
      0.0009) and for slope (0.738-1.168), indicating that both methods are
      interchangeable, although not identical.

PMID- 12209898
TI  - Effect of bleaching agents on the fluoride release and microhardness of dental
      materials.
AB  - The use of bleaching agents has become a popular procedure for whitening teeth.
      Recently introduced polyacid-modified composite resins (compomers) have several
      favorable features, such as improved physical properties and fluoride release.
      Because these two materials have many possibilities to interact in the oral
      cavity during dental treatment, it is necessary to understand such interaction.
      To evaluate the effect of a bleaching agent on dental restoratives, three
      compomers were photopolymerized and then bleached for 1, 2, 3 and 5 days with the
      use of 30% hydrogen peroxide. Fluoride release, surface microhardness, and
      surface modifications were evaluated. It was found that the cumulative fluoride
      release was found to be linearly correlated to the tested periods of bleaching in
      all compomers. Among the tested compomers, F2000 showed the highest cumulative
      fluoride release. Bleached compomers became soft because of surface degradation,
      so the surface microhardness decreased. F2000 showed an apparent crack formation
      that was not observed in other compomers. The nearly linear correlation between
      the filler content and microhardness was found in the control samples. However,
      the same correlation was not observed after the compomers were stored in a
      bleaching agent or distilled water.

PMID- 12209899
TI  - Evaluation of feasibility of hydroxyapatite putty as a local hemostatic agent for
      bone.
AB  - Although bone wax is known to cause an inflammatory reaction in soft tissue and a
      delay of bone healing, it is usually the first choice to arrest bleeding from
      bone. Hydroxyapatite (HAP) putty is proposed here. This study evaluated the
      feasibility of HAP putty with respect to whether or not it has potential value as
      a hemostatic agent for bone. First, the adhesive strength of HAP putty to bone
      was evaluated. The adhesive strength of HAP putty to wet bone was much higher
      when compared with that of bone wax, even though the adhesive strengths of HAP
      putty and bone wax to dry bone were equivalent. Next, to evaluate the hemostatic
      ability of HAP putty, bony defects were made in rabbits. HAP putty could arrest
      bleeding from bone within 3 min. However, when the hemostasis was performed with
      bone wax, bleeding was arrested within 8 min. Thus, HAP putty showed better
      hemostatic ability than bone wax. Finally, the tissue response to HAP putty in
      rabbit subcutaneous tissue was evaluated. Histological observation revealed a
      slight inflammatory response around HAP putty, whereas bone wax was surrounded by
      moderate inflammatory tissue. In conclusion, HAP putty has good potential value
      to be a hemostatic agent for bone because it has strong adhesion, good hemostatic
      ability, and biocompatibility.

PMID- 12209900
TI  - Morphologic and immunohistochemical observations of tissues surrounding retrieved
      transvenous pacemaker leads.
AB  - Immunohistochemical and morphologic techniques were employed to evaluate the
      tissue response around chronically implanted pacing leads. Seventeen leads were
      retrieved from 12 patients. Leads were extracted by direct manual traction (1),
      extraction with sheaths and locking stylets (1), or with by a combination of
      mechanical tools and Excimer laser sheaths (15). Mean lead implantation time was
      5.6 years (range 1-8 years). Frozen sections, 6-8 microm thick, were incubated
      with antibodies against HLA-DR antigen, endothelial cells, macrophages, T cells,
      plasma cells, fibrinogen, and interleukin-1beta. Prominent morphologic
      observations were fibrous encapsulations of the leads. Immunohistochemical
      analysis revealed a tissue generally devoid of inflammatory and immune cells. The
      fibrous capsule surrounding the lead was partially or completely covered with a
      monolayer of CD34 expressing endothelial cells. The results from this study
      provide useful information in design and material selection for pacemaker leads.
      Endothelialization of the fibrous encapsulation indicates a functionalization of
      blood-contacting surfaces around pacemaker materials, thus providing a mechanism
      for long-term persistence of foreign materials in the blood. The laser method
      allowed an efficient extraction of pacemaker leads without damage to the studied
      tissues, as suggested by the presence of immunolabeled cells close to the cut
      surfaces.

PMID- 12209901
TI  - Gamma irradiation alters fatigue-crack behavior and fracture toughness in 1900H
      and GUR 1050 UHMWPE.
AB  - Pitting and delamination remain causative factors of polyethylene failure in
      total knee replacement. Gamma irradiation induces cross linking in ultra-high
      molecular-weight polyethylene, which has been shown to improve wear resistance.
      Irradiation may reduce fracture toughness and fatigue strength, however, and the
      effects of irradiation are dependent upon the resin, processing technique, and
      radiation dose. The effects of varying levels of gamma irradiation (0, 33, 66,
      and 100 kGy) on the fracture toughness and fatigue-crack resistance of UHMWPE,
      isostatically molded from 1900H and GUR 1050 resins, were examined. Paris law
      regressions were performed to quantify fatigue-crack propagation rates as
      functions of change in stress intensity, and J-integral methods were used to
      quantify the elastic-plastic fracture toughness. The results indicated that gamma
      irradiation reduced the resistance of both materials to fatigue-crack growth, and
      that the reductions were radiation dosage and resin dependent. Irradiation at any
      level was detrimental to the fracture toughness of the 1900H specimens.
      Irradiation at 33 kGy increased fracture toughness for the GUR 1050 specimens,
      and substantial reductions were observed only at the highest irradiation level.
      Scanning electron microscopy of the fracture surface revealed diamond-like
      fracture patterns of the nonirradiated specimens indicative of ductile,
      multilevel fracture. Pronounced striations were apparent on these fracture
      surfaces, oriented perpendicular to the direction of crack growth. The striations
      appeared as folds in surface layers of the GUR 1050 specimens. At the highest
      irradiation levels, the striations were nearly eliminated on the fracture
      surfaces of the 1900H specimens, and were markedly less severe for the GUR 1050.
      These results demonstrated that at higher irradiation levels the materials became
      more brittle in fatigue, with less ductile folding and tearing of the fracture
      surfaces.

PMID- 12209902
TI  - Carbon dioxide extraction of residual chloroform from biodegradable polymers.
AB  - Biodegradable polymeric devices for drug delivery and tissue engineering are
      often fabricated with the use of organic solvents and may still contain
      significant amounts of solvent (> 1 wt%) even after aggressive vacuum drying.
      This excess solvent can interfere with tissue response and the mechanical
      properties of the devices. The aim of this article is to demonstrate that liquid
      CO(2) extraction can be used to reduce residual solvent in dense poly(L-lactide
      co-glycolide) devices to 50 ppm relatively quickly and with minimal changes in
      architecture under some conditions. Two liquid CO(2) extraction systems were
      developed to examine the removal of residual solvents from bar-shaped PLGA
      devices: (1) a low-pressure (1400 psi) batch system, and (2) a high-pressure
      (5000 psi) continuous-flow system. Eight hours of extraction in the high-pressure
      system reduced residual chloroform in 3 mm thick bars below the 50-ppm target. A
      simple Fickian diffusion model was fit to the extraction results. Diffusion
      coefficients ranged from 1.10 x 10(-6) cm(2)/s to 2.64 x 10(-6) cm(2)/s. The
      model predicts that approximately 1 h is needed to dry 1-mm bars to chloroform
      levels below 50 ppm, and 7 h are needed for 3 mm thick bars. The micro- and
      macroarchitectures of porous PLGA scaffolds created by particulate leaching were
      not significantly altered by CO(2) drying if the salt used to make the pores was
      not removed before drying.

PMID- 12209903
TI  - Biomembranes enriched with TGFbeta1 favor bone matrix protein expression by human
      osteoblasts in vitro.
AB  - The use of growth factors in oral tissue regeneration is currently under
      investigation. When growth factors are combined with commercial materials, the in
      vitro mechanisms of action still remain unclear. The present study first
      evaluated the capacity of barrier membranes, used in oral surgery, to sequester
      TGFbeta(1). Resorbable HYAFF, paroguide, poly DL-lactide and nonresorbable PTFE
      membranes were immersed in MEM containing 0.2 ng (125)I-TGFbeta(1) for different
      periods of time. It was found that HYAFF membrane and paroguide sequestered the
      most TGFbeta(1), which was then released in its active form (as shown by the
      CCL64 cell line bioassay). Untreated membranes and membranes enriched with
      TGFbeta(1) were then used as substrate for human bone cells to evaluate the
      synthesis of the osteoblast phenotype, as indicated by specific parameters.
      Results showed that membranes enriched with TGFbeta(1) increased alkaline
      phosphatase activity, collagen, and osteocalcin production more than untreated
      membranes. HYAFF and paroguide membranes, which sequestered the most of
      TGFbeta(1), were the most suitable for stimulating bone matrix proteins.

PMID- 12209904
TI  - Biological reactivity of zirconia-hydroxyapatite composites.
AB  - Materials and devices intended for end-use applications as implants and medical
      devices must be evaluated to determine their biocompatibility potential in
      contact with physiological systems. The use of standard practices of biological
      testing provides a reasonable level of confidence concerning the response of a
      living organism to a given material or device, as well as guidance in selecting
      the proper procedures to be carried out for the screening of new or modified
      materials. This article presents results from cytotoxicity assays of cell
      culture, skin irritation, and acute toxicity by systemic and intracutaneous
      injections for powders, ceramic bodies, and extract liquids of hydroxyapatite
      (HA), calcia partially stabilized zirconia (ZO), and two types of zirconia
      hydroxyapatite composites (Z4H6 and Z6H4) with potential for future use as
      orthopedic and dental implants. They indicate that these materials present
      potential for this type of application because they meet the requirements of the
      standard practices recommended for evaluating the biological reactivity of ATCC
      cell cultures (CCL1 NCTC clone 929 of mouse connective tissue and CCL 81 of
      monkey connective tissue) and animals (rabbit and mouse) with direct or indirect
      patient contact, or by the injection of specific extracts prepared from the
      material under test. In addition, studies involving short-term intramuscular and
      long-term implantation assays to estimate the reaction of living tissue to the
      composites studied, and investigations on long-term effects that these materials
      can cause on the cellular metabolism, are already in progress.

PMID- 12209905
TI  - Extracellular matrix of human amnion manufactured into tubes as conduits for
      peripheral nerve regeneration.
AB  - The human amnion consists of the epithelial cell layer and underlying connective
      tissue. After removing the epithelial cells, the resulting acellular connective
      tissue matrix was manufactured into thin dry sheets called amnion matrix sheets.
      The sheets were further processed into tubes, amnion matrix tubes (AMTs), of
      varying diameters, with the walls of varying numbers of amnion matrix sheets with
      or without a gelatin coating. The AMTs were implanted into rat sciatic nerves.
      Regenerating nerves extended in bundles through tubes of 1-2 mm in diameter and
      further elongated into host distal nerves 1-3 weeks after implantation.
      Morphometrical analysis of the regenerated nerve cable at the middle of each
      amnion matrix tube 3 weeks after implantation was performed. The average numbers
      of myelinated axons were almost the same (ca. 80-112/10(4) microm(2)) in AMTs of
      1-2 mm in diameter, as in the normal sciatic nerve (ca. 95/10(4) microm(2)). No
      myelinated fibers were found in AMTs composed of multiple thin tubes of 0.2 mm in
      diameter. The myelinated axons were thinner in implanted tubes than those in the
      normal sciatic nerve. The rate of occurrences of myelinated axons less than 4
      microm in diameter was significantly higher in the AMTs, whereas axons in the
      normal sciatic nerve were diverse in distribution, with the highest population at
      8-12 microm in diameter. Reinnervation to the gastrocnemius muscle was
      demonstrated electrophysiologically 9 months after implantation. It was concluded
      that the extracellular matrix sheet from the human amnion is an effective conduit
      material for peripheral nerve regeneration.

PMID- 12209906
TI  - Histological examination of beta-tricalcium phosphate graft in human femur.
AB  - Prominent osteoconductive activity and the biodegradable nature of beta
      tricalcium phosphate (beta-TCP) for bone grafts in animal experiments has been
      reported. A new type of beta-TCP has been manufactured at extraordinarily high
      purity and has been available as potent bone grafting substitute for clinical
      use. The histological features of grafted beta-TCP in human bone have been
      analyzed. A 33-year-old female with a bone tumor of the proximal femur underwent
      curettage and beta-TCP graft under the diagnosis of probable benign fibrous
      dysplasia. Four weeks later, the proximal femur, including the grafted beta-TCP
      was resected because of the final diagnosis of the curettaged materials was
      osteosarcoma. The resected specimen revealed abundant direct new bone apposition
      on beta-TCP. There was no cartilaginous tissue or enchondral ossification. Bone
      formation was more prominent in the periphery of the grafted area than in the
      center. There was a considerable number of osteoclast-like giant cells
      surrounding the beta-TCP. This case illustrated that highly purified beta-TCP had
      prominent osteoconductive activity and biodegradable nature in human bone.

PMID- 12209907
TI  - The peak-amplitude method of vibration analysis for nondestructively studying the
      structural integrity of dental gypsum.
AB  - The aim of this work was to estimate the internal friction of dental gypsum
      products by measuring their loss factor with the use of the peak-amplitude method
      of vibration analysis. Cylindrical specimens for the measurement of compressive
      strength and rectangular specimens for the measurement of loss factor were
      constructed from plaster, dental stone, and high-strength dental stone. The loss
      factor was measured by vibrating specimens up to their resonance frequency, where
      the peak-amplitude method was applied. It was found that the peak-amplitude
      method is a simple, quick, and reliable method for measuring the loss factor of
      dental gypsum products. Furthermore, it was also found that the drying process of
      these materials reduces their internal friction and hence lowers the loss factor,
      whereas the use of excess water in their formulation has the reverse result. The
      correlation between strength and loss factor was found to be strongly negative.
      The results of this study are in agreement with the results from research on the
      microstructure of dental gypsum.

PMID- 12209909
TI  - Effect of ball milling on the processing of bone substitutes with calcium
      phosphate powders.
AB  - Decreasing the microscale morphology of synthetic bone substitutes is of primary
      importance in order to enhance the morphology of the surface of the material,
      which is directly in contact with osteoconductive cells when it is implanted in
      bone. The aim of this study was to investigate the influence of ball milling of
      slurries on the microscale morphology of hydroxyapatite and tricalcium phosphate
      bone substitutes and the influence on their processing. Ball milling appeared to
      be a successful method in order to raise the sintering reactivity of the powders,
      that is, to decrease the sintering temperature and microstructural morphology of
      the material. However, it was demonstrated that ball milling had a great
      influence on dispersion, which became very difficult under long milling times
      because of dissolution of the calcium phosphate powders. Due to dissolution,
      ionic species were generated in the slurry and interfered with the dispersing
      agent. Moreover a reprecipitation process occurred simultaneously, and large
      particles of the most stable phase (HAP) formed. The presence of such large
      particles generated stress gradients and cracks in the material during the
      sintering stage.

PMID- 12209908
TI  - Chitosan-alginate PEC membrane as a wound dressing: Assessment of incisional
      wound healing.
AB  - Flexible, thin, transparent, novel chitosan-alginate polyelectrolyte complex
      (PEC) membranes, cast from aqueous suspensions of chitosan-alginate coacervates
      with CaCl(2), were evaluated as potential wound-dressing materials. MTT and NR
      assays suggested that the chitosan-alginate PEC membranes and their aqueous
      extracts were nontoxic towards mouse and human fibroblast cells. Cell growth was
      also not hindered by co-incubation with the membranes. Compared to conventional
      gauze dressing, the PEC membranes caused an accelerated healing of incision
      wounds in a rat model. Wounds closed at 14 days postoperatively, and histological
      observations showed mature epidermal architecture with keratinized surface of
      normal thickness and a subsided inflammation in the dermis. This was followed by
      an excellent remodeling phase with organized thicker collagen bundles and mature
      fibroblasts at 21 days postoperative. Control wounds continued to show signs of
      an active inflammatory phase under scab on Day 21. Closure rate and appearance of
      PEC membrane-treated wounds were comparable with Opsite(R)-treated wounds. On the
      basis of its biocompatibility and wound-healing efficacy, the chitosan-alginate
      PEC membrane can be considered for wound-dressing applications.

PMID- 12209910
TI  - Theoretical prediction and experimental determination of the effect of mold
      characteristics on temperature and monomer conversion fraction profiles during
      polymerization of a PMMA-based bone cement.
AB  - The present work is concerned with applications of a kinetic model for free
      radical polymerization of a polymethylmethacrylate-based bone cement.
      Autocatalytic behavior at the first part of the reaction as well as a diffusion
      control phenomenon near vitrification are described by the model. Comparison of
      theoretical computations with experimental measurements for the temperature
      evolution during batch casting demonstrated the capacity of the proposed model to
      represent the kinetic behavior of the polymerization reaction. Temperature
      evolution and monomer conversion were simulated for the cure of the cement in
      molds made of different materials. The maximum monomer conversion fraction was
      markedly influenced by the physical properties of the mold material. The
      unreacted monomer acts as a plasticizer that influences the mechanical behavior
      of the cement. Hence, the same cement formulation cured in molds of different
      materials may result in different mechanical response because of the differences
      in the amounts of residual monomer. Standardization of the mold type to prepare
      specimens for the mechanical characterization of bone cements is recommended.
      Theoretical prediction of temperature evolution during hip replacement indicated
      that for cement thickness lower than 6 mm the peak temperature at the bone-cement
      interface was below the limit stated for thermal injury (50 degrees C for more
      than 1 min). The use of thin cement layers is recommended to diminish the risk of
      thermal injury; however, it is accompanied by an increase in the amount of
      unreacted monomer present in the cured material.

PMID- 12209911
TI  - Cytotoxicity of ingredients of various dental materials and related compounds in
      L2- and A549 cells.
AB  - Various ingredients of dental materials and related compounds were tested for
      cytotoxicity in two alveolar epithelial cell lines (L2 and A549 cells). Release
      of lactate dehydrogenase (LDH) from cells was measured after incubation with the
      test substances for time intervals up to 48 h and expressed as percentage of
      total LDH content of lysed cells. Furthermore, the glutathione content of cells
      was determined in the nonmalignant L2 cells. Additionally, cell viability was
      assessed by microscopic examination. The highest cytotoxicity was observed with
      mercury compounds (methylmercuric chloride and mercury dichloride) in the range
      of 5-20 micromol/l. The composite components 2-hydroxyethylmethacrylate (HEMA)
      and triethleneglycoldimethacrylate (TEGDMA) showed time- and concentration
      dependent effects of cytotoxicity at high concentrations (about 1-5 mmol/l). A
      time dependence for GSH decrease was mainly found for the composite components up
      to 12 h of cellular exposure. L2 cells were more sensitive to both mercury and
      composite compounds than A549 cells. Gold compounds (sodiumaurothiomalate and
      gold particles < 1.5 microm) did not produce any sign of toxic reactions. A time
      dependent increased toxicity in pulmonary cell lines was found for the composite
      components HEMA and TEGDMA, but not for mercury and gold compounds.

PMID- 12209912
TI  - A field-focusing device to increase power output of ThermoRod trade mark implants
      for thermal ablation of tissue.
AB  - Induction heating of small, cylindrical ferromagnetic implants (1.4 cm long and 1
      mm in diameter) is a method for treating deep-seated tumors. These implants, or
      ThermoRods trade mark, are placed within a lesion in 1-cm(2) arrays and are
      exposed to an alternating magnetic field. The implants absorb energy from that
      field and transfer it as heat to the surrounding tissue. Each ThermoRod trade
      mark offers approximately 400 mW of power, and to kill cells, the target
      temperature must be greater than 42 degrees C. In this work, a magnetic field
      focusing device is employed to concentrate the induced magnetic flux toward a
      local region near the base of the prostate to increase the power output of
      proximal ThermoRods trade mark. This, in turn, allows for more complete thermal
      ablation of lesions near the base of the prostate where the heat-sink
      characteristics of the bladder can cause significant power losses. Boundary
      element analysis and in vitro testing have shown that the use of a ferrofluid
      based field-focusing device can lead to a significant increase in power output of
      approximately 25% and 13%, respectively, of proximal ThermoRods trade mark. These
      preliminary results indicate that the incorporation of such a ferrofluid-based
      focusing device into ThermoRod trade mark treatments is promising for the
      avoidance of significant power loss and for assuring complete thermal ablation of
      prostatic lesions.

PMID- 12209913
TI  - Effect of surface conditions on the color of dental resin composites.
AB  - The objectives of this study were to evaluate the effect of surface conditions of
      dental resin composites on the measured color depending on the measuring geometry
      (SCE, SCI), and to determine the color difference (DeltaE*) caused by varied
      surface conditions. Color and surface roughness (Ra) of five brands of resin
      composites of A2 shade were measured after polymerization and polishing with 600
      , 1000-, or 1500-grit SiC paper. Color was measured according to the CIE L*a*b*
      color scale. DeltaE* between different surface conditions was calculated by the
      equation DeltaE* = [(DeltaL*)(2) + (Deltaa*)(2) + (Deltab*)(2)](1/2). Before
      polishing, CIE L* values with the SCE were significantly lower than those
      measured with the SCI. Before polishing, DeltaE* values depending on the
      measuring geometry were very high (3.78-5.93). However, those after polishing
      were lower than 1.61. CIE L* values increased after polishing (p < 0.05) with the
      SCE; however, they were not changed with the SCI. DeltaE* values between Mylar
      covered and 600-grit polished specimens were 4.20-5.99 with the SCE and 0.27-1.46
      with the SCI. Measurement with the SCE geometry may result in accurate color
      determination, which reflects the surface conditions of dental restorative
      materials. DeltaE* values measured with the SCE between the specimens of
      different surface conditions were significantly higher than those with the SCI (p
      < 0.05).

PMID- 12209914
TI  - The electrochemical behavior of Ti-6Al-7Nb alloy with and without plasma-sprayed
      hydroxyapatite coating in Hank's solution.
AB  - The electrochemical behavior of Ti-6Al-7Nb alloy with and without plasma-sprayed
      hydroxyapatite (HA) coating was investigated in Hank's balanced salt solution at
      37 degrees C. This behavior was evaluated by analyzing both corrosion potential
      variation with time curves and potentiodynamic polarization curves. The
      polarization curves were determined both in aerated and deaerated solutions. It
      was found that the corrosion potential of uncoated sample is always more noble
      than that of coated one. In aerated solutions the polarization curve of a coating
      free alloy presents a typical passive/transpassive behavior, which is absent in
      the HA-coated alloy and in deaerated solution for both coated and uncoated
      conditions. In the latter polarization curves, the current density continuously
      increases with the increase of the potential. The corrosion rate determined from
      polarization curves is higher for HA-coated alloys, but it still can be
      considered negligible (less than 1 microA/cm(2)).

PMID- 12209915
TI  - The influence of system compliance and sample geometry on composite
      polymerization shrinkage stress.
AB  - The objective of this study was to use finite-element analysis to model
      tensilometer tests of polymerizing dental composites. A typical sample in
      polymerization shrinkage stress tests is shaped like a flat disk, that is, has a
      high aspect ratio (ratio of diameter to height). In the experimental literature
      it is implied that the induced stress state in the flat disk composite samples is
      uniaxial. Three published tensilometer tests of curing dental composite samples
      with similar high aspect ratios (varying from 3 to 5) were modeled, but with test
      configurations having low, intermediate and high relative compliance (a tenfold
      variation). With the use of linear elastic finite element analysis, an
      instantaneous volumetric shrinkage of 1% was applied to the composite via the
      thermal analogy and the following questions were addressed: 1. Does the
      numerically predicted state of stress in composite samples tested in this fashion
      differ substantially from the uniaxial stress state assumed in the experiments?2.
      How do the numerically predicted stresses compare with the experimentally
      determined nominal stresses?3. Does compliance of the mountings influence the
      numerically predicted stress state? The finite-element results predicted a
      complex triaxial stress state that was strongly influenced by the compliance of
      the mountings. For the low and intermediate system compliance the model
      overpredicted the polymerization contraction stress, as would be anticipated due
      to the inability of the model to account for viscoplastic flow. For high system
      compliance, the numerical and experimental stress values were in better
      agreement, mainly because the linear elastic mountings accounted for most of the
      measured system compliance.

PMID- 12209916
TI  - A new vascular prosthesis coated with polyamino-acid urethane copolymer (PAU) to
      enhance endothelialization.
AB  - Clinically available synthetic ePTFE vascular grafts frequently fail when used
      for small-diameter arterial substitution. The lower long-term patency of ePTFE
      grafts is due mainly to thrombogenicity and poor healing. We developed a new
      small-diameter (1.5-mm) ePTFE vascular prosthesis coated with polyamino-acid
      urethane copolymer (PAU) to enhance endothelialization. Coating with PAU made the
      hydrophobic ePTFE vascular graft hydrophilic. Scanning electron microscopy (SEM)
      observation showed that PAU was homogeneously coated on the ePTFE graft while
      maintaining the graft's porous structure. Fourier transform infrared attenuated
      total reflectance (FTIR-ATR) spectra showed PAU was present on graft inner
      surfaces. Noncoated and PAU-coated ePTFE vascular grafts were implanted into the
      rat abdominal aorta and evaluated within 1 week and at 8 weeks after
      implantation. We evaluated the extent of neoendothelialization by SEM, light
      microscopy, and immunohistochemical staining. Noncoated grafts showed partial
      endothelialization at proximal and distal areas of grafts but none at midsection.
      One-percent PAU-coated grafts showed incomplete neoendothelialization, but
      endothelial cells were observed in the midsection of grafts. Three-percent PAU
      coated ePTFE grafts showed complete endothelialization with typical endothelial
      cell layers under SEM and histologic observation. Immunohistochemical staining
      also showed that an endothelial cell lining positively reacted with anti-von
      Willebrand factor (endothelial cell marker) antibody. We conclude that PAU-coated
      ePTFE vascular grafts enhance endothelialization.

PMID- 12209917
TI  - Characterization of cartilagenous tissue formed on calcium polyphosphate
      substrates in vitro.
AB  - Successful joint resurfacing by tissue-engineered cartilage has been limited, in
      part, by an inability to secure the implant to bone. To overcome this, we have
      developed the methodology to form a cartilage implant in vitro consisting of a
      layer of cartilagenous tissue overlying a porous, biodegradable calcium
      polyphosphate (CPP) substrate. As bone will grow into the CPP after implantation,
      it will result in anchorage of the cartilage. In this study, the cartilagenous
      tissue formed in vitro after 8 weeks in culture was characterized and compared to
      native articular cartilage. Light microscopic examination of histological
      sections showed that there was a continuous layer of cartilagenous tissue on, and
      integrated with the subsurface of, the CPP substrate. The in vitro-formed tissue
      achieved a similar thickness to native articular cartilage (mean +/- SEM: in
      vitro = 0.94 +/- 0.03 mm; ex vivo = 1.03 +/- 0.01 mm). The cells in the in vitro
      formed tissue synthesized large proteoglycans (Kav +/- SEM: in vitro = 0.27 +/-
      0.01; ex vivo = 0.27 +/- 0.01) and type II collagen similar to the chondrocytes
      in the ex-vivo cartilage. The in vitro-formed tissue had a similar amount of
      proteoglycan (GAG microg/mg dry wt.: in vitro = 198 +/- 10; ex vivo = 201 +/- 13)
      but less collagen than the native cartilage (hydroxyproline microg/mg dry wt.: in
      vitro = 21 +/- 1; ex vivo = 70 +/- 8). The in vitro-formed tissue had only about
      3% of the load-bearing capacity and stiffness of the native articular cartilage,
      determined from unconfined mechanical compression testing. Although low, this was
      within the range of properties reported by others for tissue-engineered
      cartilage. It is possible that the limited load-bearing capacity is the result of
      the low collagen content and further studies are required to identify the
      conditions that will increase collagen synthesis.

PMID- 12209918
TI  - Human monocyte response to retrieved polymethylmethacrylate particles.
AB  - The purpose of this study was to compare retrieved polymethylmethacrylate (PMMA)
      particles from failed total hip arthroplasties in terms of size, shape, and the
      response of human monocytes with commercially available particles. PMMA particles
      were isolated from peri-implant tissues of five failed cemented total hip
      arthroplasties using tissue digestion and a sucrose density gradient technique.
      Prepolymerized cement powder and those from which barium sulfate had been removed
      were examined for comparison. After exposure of peripheral human monocytes to
      PMMA particles, tumor necrosis factor-alpha and interleukin-6 in medium were
      measured by using enzyme-linked immunosorbent assays. Image analysis revealed
      that retrieved particles were larger (retrieved: 1.24 microm; prepolymerized
      cement powder: 0.83 microm; barium sulfate-free powder: 0.87 microm) and were
      more irregular in shape and rougher than commercially available particles.
      Cytokine release was increased by all PMMA particle species. However,
      commercially available PMMA particles stimulated the release of necrosis factor
      alpha and interleukin-6 more strongly than did retrieved particles at very high
      doses. The observed difference in monocyte response might be due to the volume of
      the challenged particles. Another possible reason for the difference might be
      alteration of the surface chemistry of particles in situ and the difference in
      surface morphology between them.

PMID- 12209919
TI  - Theoretical investigation of elastic flexural properties for multistranded
      orthodontic archwires.
AB  - The bending and torsional stresses during flexure were detailed and simplified
      for a single twisted strand, which emulates a spring. General expressions were
      derived to evaluate the elastic properties (i.e., strength, stiffness, and range)
      of multistranded wires by combining the effects of a number of outer twisted
      strands, with or without an inner strand. Specific expressions were solved for
      single-stranded, twisted, and coaxial wires. Initially, we considered the
      following multistranded wire configurations: two- (twin), three- (triple), four
      strand (quad) twisted, and coaxial wires. The elastic properties of the twin and
      quad wires were essentially subsets of the triple wire. For a given overall wire
      diameter (D) and helix angle (alpha), the ranges of multistranded wires were
      independent of wire configurations. By varying the alpha from 45 to 85 degrees,
      the D from 0.394 to 0.546 mm (15.5 to 21.5 mil), and the stress at the
      proportional limit from 1.03 to 3.28 GPa (150 to 475 ksi), the theoretical
      elastic properties of triple and coaxial stainless steel wires matched many of
      the properties of conventional nickel titanium leveling wires.

PMID- 12209920
TI  - Bone formation by rat bone marrow cells cultured on titanium fiber mesh: effect
      of in vitro culture time.
AB  - The objective of this study was to examine the effect of cell culture time on
      bone formation by rat bone marrow cells seeded in titanium fiber mesh. As a
      seeding technique, a high cell suspension was used (3 x 10(6) cells/mL).
      Therefore, 30 meshes were repeatedly rotated in a 10 mL tube (containing 30 x
      10(6) cells) on a rotation plate (2 rpm) for 3 h. Osteogenic cells were cultured
      for 1, 4, and 8 days on titanium fiber mesh and finally implanted subcutaneously
      in rats. Meshes without cells were also implanted subcutaneously in rats. DNA and
      scanning electron microscopy (SEM) analyses and calcium measurements determined
      cellular proliferation and differentiation during the in vitro incubation period
      of the mesh implants. Four weeks after implant insertion, the animals were
      sacrificed. The implants, with their surrounding tissue, were retrieved and
      prepared for histologic evaluation and calcium measurements. DNA analysis of the
      in vitro experiment showed a lag phase from day 1 through day 4, but a 42%
      increase in DNA between days 4 and 8. SEM and calcium measurements indicated an
      increase in calcium from day 1 to day 4, yet only a small but significant
      increase from days 4 to 8. Histologic analysis demonstrated that bone was formed
      in all day 1 and day 4 implants, and that the bone-like tissue was present
      uniformly through the meshes. The bony tissue was morphologically characterized
      by osteocytes embedded in a mineralized matrix, with a layer of osteoid and
      osteoblasts at the surface. The day 8 implants showed only calcium phosphate
      deposition in the titanium fiber mesh. Calcium measurements of the implants
      revealed that calcification in day 1 implants was significantly higher (p < 0.05)
      compared to day 4 and day 8 implants. No significant difference in calcium
      content existed between day 4 and day 8 implants. On the basis of our results, we
      conclude that 1) bone formation was generated more effectively in osteogenic
      cells by a short culture time after seeding in titanium fiber mesh; 2) dynamic
      cell seeding is probably more effective than static cell seeding; and 3)
      selection of the right cells from the heterogenous bone marrow population remains
      a problem.

PMID- 12209921
TI  - Collagen fiber disruption occurs independent of calcification in clinically
      explanted bioprosthetic heart valves.
AB  - The durability of bioprosthetic heart valves (BHV) is severely limited by tissue
      deterioration, manifested as calcification and mechanical damage to the
      extracellular matrix. Extensive research on mineralization mechanisms has led to
      prevention strategies, but little work has been done on understanding the
      mechanisms of noncalcific matrix damage. The present study tested the hypothesis
      that calcification-independent damage to the valvular structural matrix mediated
      by mechanical factors occurs in clinical implants and could contribute to porcine
      aortic BHV structural failure. We correlated quantitative assessment of collagen
      fiber orientation and structural integrity by small angle light scattering (SALS)
      with morphologic analysis in 14 porcine aortic valve bioprostheses removed from
      patients for structural deterioration following 5-20 years of function.
      Calcification of the explants varied from 0 (none) to 1+ (minimal) to 4+
      (extensive), as assessed radiographically. SALS tests were performed over entire
      excised cusps using a 0.254-mm spaced grid, and the resultant structural
      information used to generate maps of the local collagen fiber damage that were
      compared with sites of calcific deposits. All 42 cusps showed clear evidence of
      substantial noncalcific structural damage. In 29 cusps that were calcified,
      structural damage was consistently spatially distinct from the calcification
      deposits, generally in a distribution similar to that noted in porcine BHV
      subjected to in vitro durability testing. Our results suggest a mechanism of
      noncalcific degradation dependent on cuspal mechanics that could contribute to
      porcine aortic BHV failure.

PMID- 12209922
TI  - Optimization of monomethoxy-polyethylene glycol grafting on the pancreatic islet
      capsules.
AB  - As a new approach to islet transplantation, biocompatible monomethoxy
      poly(ethylene glycol) (mPEG) was chemically grafted onto the pancreatic islet
      capsule. The aim of this study was to determine the optimal conditions for
      completely covering the islet by the mPEG while maintaining a high viability of
      islets according to the reaction time and the repeating number of the reaction.
      By grafting the fluorescein-PEG instead of mPEG, we determined the optimal mPEG
      grafting time as 1 h, during which time the procedure did not reduce islet
      viability. Insulin secretion from islets where the mPEG was grafted on for 3
      times was similar to that of control islets. Moreover, the mPEG-grafted islets
      rapidly responded to the changes in the glucose concentration in the same pattern
      as did control islets. These results showed that mPEG grafting did not damage the
      function of islets. In conclusion, when the mPEG grafting was performed for 1 h
      and repeated twice with 1-day culture between each mPEG-grafting step, the mPEG
      completely covered the islet capsules without any damage to the viability and
      function of the islets. The main advantage of mPEG grafting on the islet capsule
      is that it can protect the islet against the host's immune system without
      increasing the islet size so that it can be administered into the portal vein by
      the catheter.

PMID- 12209923
TI  - Calcium phosphate/chitosan composite scaffolds for controlled in vitro antibiotic
      drug release.
AB  - Macroporous chitosan scaffolds reinforced by beta-tricalcium phosphate (beta-TCP)
      and calcium phosphate invert glasses were fabricated using a thermally induced
      phase separation technique. These porous composite materials were specially
      designed as both a drug carrier for controlled drug release and a scaffold for
      bone regeneration. The controlled drug release of antibiotic gentamicin-sulfate
      (GS) loaded scaffolds and morphology of osteosarcoma MG63 cells cultured on the
      scaffolds were studied. In comparison with the GS loaded pure chitosan scaffolds,
      the initial burst release of GS was decreased through incorporating calcium
      phosphate crystals and glasses into the scaffolds, and the sustained release for
      more than 3 weeks was achieved. The possible mechanisms for the controlled drug
      release were investigated by SEM, FTIR, and measurements of the pH values of the
      PBS solution during the drug release test. SEM micrographs showed no apparent
      morphological differences for osteoblastic cells grown on the pure chitosan
      scaffolds and those grown on composite scaffolds. The cells were attached and
      migrated on these scaffolds, and exhibited a biological appearance, suggesting a
      good cellular compatibility.

PMID- 12209924
TI  - Liquid acrylate-endcapped biodegradable poly(epsilon-caprolactone-co-trimethylene
      carbonate). I. Preparation and visible light-induced photocuring characteristics.
AB  - Photocurable liquid biodegradable copolymers were prepared by ring-opening
      copolymerization of epsilon-caprolactone (CL) and trimethylene carbonate (TMC) in
      the presence of a multifunctional hydroxyl group-bearing substance (di-, tri-,
      and tetra-functional alcohol and poly(ethylene glycol) (PEG) and its four
      branched derivative) as an initiator and subsequent endcapping with acryloyl
      chloride at their hydroxyl terminals. These multifunctional, viscous liquid
      copolymers (molecular weights; approximately 2 x 10(3) to 7 x 10(3) g/mol) were
      converted to crosslinked solids by visible-light irradiation in the presence of
      camphorquinone as an initiator. The photocuring rate of these copolymers was
      enhanced by both higher functionality and lower molecule weight of the copolymers
      used. The photocuring rate depended on the amount of reducing agent (methacrylic
      acid 2-dimethylaminoethyl ester). Upon immersion in a phosphate buffer solution
      (pH 7.4), hydrolysis occurred preferentially on the surface except for photocured
      PEG-based copolymers that were degraded faster via both surface erosion and bulk
      degradation than low molecular weight alcohols-based copolymers. Cylindrical
      photocured constructs prepared by photoirradiation to the whole body in a mold
      filled with the liquid copolymer was demonstrated as an example of shape
      fabrication of biodegradable biomedical devices.

PMID- 12209925
TI  - Liquid acrylate-endcapped biodegradable poly(epsilon-caprolactone-co-trimethylene
      carbonate). II. Computer-aided stereolithographic microarchitectural surface
      photoconstructs.
AB  - Advanced micromedical devices may require computer-aided photofabrication, by
      which microarchitectural surface design and entire macroshaped body design are
      feasible. Liquid acrylate-endcapped poly(epsilon-caprolactone-co-trimethylene
      carbonate)s, poly(CL/TMC)s, prepared using trimethylene glycol (TMG) or
      poly(ethylene glycol) (PEG) as an initiator and an acrylate group for subsequent
      terminal capping, were used as photocurable copolymers. The
      stereolithographically microarchitectured photoconstructs were prepared using a
      custom-designed apparatus with a moving ultraviolet (UV) light pen driven by a
      computer-assisted design program. The prepared photoconstructs included
      microneedles, a microcylinder and microbanks on surfaces. In vitro hydrolytic
      degradation proceeded with surface erosion when hydrophobic TMG-based photocured
      copolymers were employed, whereas very fast degradation of hydrophilic PEG-based
      photocured copolymers probably via concerted actions of surface erosion and bulk
      degradation was observed. In vivo hydrolytic behavior upon subcutaneous
      implantation in rats indicated that surface erosion proceeded for TMG-based
      photoconstructs. Anti-inflammatory drug (indomethacin) loading into microneedle
      structured surfaces minimized inflammatory reactions. The possible biomedical
      microarchitectural three dimensinal in biomedical application photoconstructs was
      discussed.

PMID- 12209926
TI  - Characterization of microrough bioactive glass surface: surface reactions and
      osteoblast responses in vitro.
AB  - The current study characterized the in vitro surface reactions of microroughened
      bioactive glasses and compared osteoblast cell responses between smooth and
      microrough surfaces. Three different bioactive glass compositions were used and
      surface microroughening was obtained using a novel chemical etching method.
      Porous bioactive glass specimens made of sintered microspheres were immersed in
      simulated body fluid (SBF) or Tris solutions for 1, 6, 24, 48, or 72 h, and the
      formation of reaction layers was studied by means of a scanning electron
      microscope/energy dispersive X-ray analysis (SEM/EDXA). Cell culture studies were
      performed on bioactive glass disks to examine the influence of surface
      microroughness on the attachment and proliferation of human osteoblast-like cells
      (MG-63). Cell attachment was evaluated by means of microscopic counting of in
      situ stained cells. Cell proliferation was analyzed with a nonradioactive cell
      proliferation assay combined with in situ staining and laser confocal microscopy.
      The microroughening of the bioactive glass surface increased the rate of the
      silica gel layer formation during the first hours of the immersion. The formation
      of calcium phosphate layer was equal between control and microroughened glass
      surfaces. In cell cultures on bioactive glass, the microrough surface enhanced
      the attachment of osteoblast-like cells but did not have an effect on the
      proliferation rate or morphology of the cells as compared with smooth glass
      surface. In conclusion, microroughening significantly accelerated the early
      formation of surface reactions on three bioactive glasses and had a positive
      effect on initial cell attachment.

PMID- 12209927
TI  - Characterization of implant materials in fetal bovine serum and sodium sulfate by
      electrochemical impedance spectroscopy. I. Mechanically polished samples.
AB  - Electrochemical impedance spectroscopy is used to monitor the long-term stability
      (up to 150 days) of mechanically polished commercial pure titanium, Ti6Al4V,
      Ti6Al7Nb, and CoCrMo alloys in 0.1M sodium sulfate and fetal bovine serum. A
      capacitive spectrum in the frequency range from 10(-3) to 10(5) Hz is always
      found and the impedance spectra can be fitted by a simple parallel RC circuit
      with a constant phase element. The open circuit potential observed in serum is
      always more cathodic and the polarization resistance (R(p)) is higher than that
      recorded in sodium sulfate solutions. The observed variation of the equivalent
      capacitance in serum bovine suggests that an adsorption layer of organic
      molecules develops on the electrode surface and it is responsible for both the
      decrease in open circuit potential and the higher R(p), because it hinders the
      oxygen evolution reaction and the charge transfer responsible for the passive
      film dissolution (or growth). Among the alloys studied, Ti6Al4V displayed the
      highest steady-state values of R(p) both in serum and in sodium sulfate.

PMID- 12209928
TI  - A jet impingement investigation of osteoblastic cell adhesion.
AB  - When designing dental and orthopedic implants, it is important to consider
      phenomena occurring at the microscopic level, particularly at the bone-implant
      interface. The presence of hard tissue at this interface is essential to implant
      viability. The integrity of this tissue-biomaterial interface is dependent on
      appropriate osteoblast functions (adhesion, matrix deposition, etc.) in the
      immediate area. Researchers have modified various materials with cell-adhesive
      peptides with the ultimate goal of controlling osteoblast functions. This study
      used microjet impingement to compare the strength of adhesion of osteoblastic
      cells (at varying populations) and fibroblasts to peptide-modified substrates in
      the presence and absence of fetal bovine serum. In the presence of the serum,
      there was no significant difference in cellular adhesion strength between
      substrates. In the absence of serum, all cells tested adhered more strongly to
      underlying substrates, and the strength of cellular adhesion was greater on
      modified surfaces than on plain glass surfaces. In the absence of serum, second
      passage osteoblastic cells generally adhered to substrates more strongly than
      first-passage osteoblastic cells; fibroblasts adhered similarly to second-passage
      osteoblastic cells. Fundamental studies such as the present increase the
      understanding of cell adhesion to various substrates--knowledge that may be
      ultimately useful in creating an optimal bone-implant interface.

PMID- 12209929
TI  - Tissue responses against immunoisolating alginate-PLL capsules in the immediate
      posttransplant period.
AB  - Alginate-polylysine (PLL) capsules are commonly applied for immunoisolation of
      living cells for the treatment of a wide variety of diseases. Large-scale
      application of the technique, however, is hampered by insufficient
      biocompatibility of the capsules with failure of the grafts as a consequence.
      Most studies addressing biocompatibility issues of alginate-PLL capsules have
      focused on the degree of overgrowth on the capsules after graft failure and not
      on the reaction against the capsules in the immediate posttransplant period.
      Therefore, capsules were implanted in the peritoneal cavity of rats and retrieved
      1, 5, and 7 days later for histological examination and X-ray photoelectron
      spectroscopy analysis for evaluation of chemical changes at the capsule surface.
      After implantation, the nitrogen signal increased from 5% on day 0, to 8.6% on
      day 7, illustrating protein adsorption on the capsule's surface. This increase in
      protein content of the membrane was accompanied by an increase in the percentage
      of overgrown capsules from 0.5 +/- 0.3% on day 1 to 3.3 +/- 1.6% on day 7. The
      cellular overgrowth was composed of monocytes/macrophages, granulocytes,
      fibroblasts, erythrocytes, multinucleated giant cells, and basophils. This
      overgrowth was not statical as generally assumed but rather dynamic as
      illustrated by our observation that at day 1 after implantation we mainly found
      monocytes/macrophages and granulocytes that on later time points were substituted
      by fibroblasts. As the inflammatory reaction predictably interfere with survival
      of encapsulated cells, efforts should be made to suppress activities or
      recruitment of inflammatory cells. These efforts may be temporary rather than
      permanent because most inflammatory cells have disappeared after 2 weeks of
      implantation.

PMID- 12209930
TI  - Fabrication and surface modification of macroporous poly(L-lactic acid) and
      poly(L-lactic-co-glycolic acid) (70/30) cell scaffolds for human skin fibroblast
      cell culture.
AB  - The fabrication and surface modification of a porous cell scaffold are very
      important in tissue engineering. Of most concern are high-density cell seeding,
      nutrient and oxygen supply, and cell affinity. In the present study, poly(L
      lactic acid) and poly(L-lactic-co-glycolic acid) (70/30) cell scaffolds with
      different pore structures were fabricated. An improved method based on
      Archimedes' Principle for measuring the porosity of scaffolds, using a density
      bottle, was developed. Anhydrous ammonia plasma treatment was used to modify
      surface properties to improve the cell affinity of the scaffolds. The results
      show that hydrophilicity and surface energy were improved. The polar N-containing
      groups and positive charged groups also were incorporated into the sample
      surface. A low-temperature treatment was used to maintain the plasma-modified
      surface properties effectively. It would do help to the further application of
      plasma treatment technique. Cell culture results showed that pores smaller than
      160 microm are suitable for human skin fibroblast cell growth. Cell seeding
      efficiency was maintained at above 99%, which is better than the efficiency
      achieved with the common method of prewetting by ethanol. The plasma-treatment
      method also helped to resolve the problem of cell loss during cell seeding, and
      the negative effects of the ethanol trace on cell culture were avoided. The
      results suggest that anhydrous ammonia plasma treatment enhances the cell
      affinity of porous scaffolds. Mass transport issues also have been considered.

PMID- 12209931
TI  - Adhesive phase separation at the dentin interface under wet bonding conditions.
AB  - Under in vivo conditions, there is little control over the amount of water left
      on the tooth and, thus, there is the danger of leaving the dentin surface so wet
      that the bonding resin undergoes physical separation into hydrophobic and
      hydrophilic-rich phases. The purpose of this study was to investigate phase
      separation in 2,2-bis[4(2-hydroxy-3-methacryloyloxy-propyloxy)-phenyl] propane
      (BisGMA)-based adhesive using molecular microanalysis and to examine the effect
      of phase separation on the structural characteristics of the hybrid layer. Model
      BisGMA/HEMA (hydroxyethl methacrylate) mixtures with/without ethanol and
      commercial BisGMA-based adhesive (Single Bond) were combined with water at
      concentrations from 0 to 50 vol%. Macrophase separation in the BisGMA/HEMA/water
      mixtures was detected using cloud point measurements. In parallel with these
      measurements, the BisGMA/HEMA and adhesive/water mixtures were cast as films and
      polymerized. Molecular structure was recorded from the distinct features in the
      phase-separated adhesive using confocal Raman microspectroscopy (CRM). Human
      dentin specimens treated with Single Bond were analyzed with scanning electron
      microscopy (SEM) and CRM mapping across the dentin/adhesive interface. The model
      BisGMA/HEMA mixtures with ethanol and the commercial BisGMA-based adhesive
      experienced phase separation at approximately 25 vol% water. Raman spectra
      collected from the phase-separated adhesive indicated that the composition of the
      particles and surrounding matrix material was primarily BisGMA and HEMA,
      respectively. Based on SEM analysis, there was substantial porosity at the
      adhesive interface with dentin. Micro-Raman spectral analysis of the
      dentin/adhesive interface indicates that the contribution from the BisGMA
      component decreases by nearly 50% within the first micrometer. The morphologic
      results in corroboration with the spectroscopic data suggest that as a result of
      adhesive phase separation the hybrid layer is not an impervious 3-dimensional
      collagen/polymer network but a porous web characterized by hydrophobic BisGMA
      rich particles distributed in a hydrophilic HEMA-rich matrix.

PMID- 12209932
TI  - The most appropriate (Ca+Zn)/P molar ratio to minimize the zinc content of
      ZnTCP/HAP ceramic used in the promotion of bone formation.
AB  - The (Ca+Zn)/P molar ratio of zinc-containing tricalcium phosphate and
      hydroxyapatite composite ceramics (ZnTCP/HAP) was investigated in the range from
      1.50 to 1.66 to reveal the minimum zinc content possible in ceramics used in the
      promotion of osteoblastic cell proliferation and bone formation. The release rate
      of zinc increased with an increase in the (Ca+Zn)/P molar ratio up to 1.64
      (ZnTCP/HAP1.64) and then decreased over 1.64 even when the zinc content of
      ZnTCP/HAP was the same. The zinc release rate of ZnTCP/HAP1.64 with a 0.21 Zn wt
      % nearly coincided with that of ZnTCP/HAP1.60 with a 0.316 Zn wt %, which was
      found be the most effective for promoting bone formation in rabbit femora. This
      means that the zinc content needed to promote bone formation can be reduced by
      34% when the (Ca+Zn)/P molar ratio is increased to 1.64. The relative growth rate
      of MC3T3-E1 cells cultured on ZnTCP/HAP1.64 had a maximum value of 1.3 at a zinc
      content of 0.51 wt %; however, a 1.20 Zn wt % is required to attain the same
      value in relative growth rate in the case of ZnTCP/HAP1.60. A reduction in zinc
      content at a certain zinc release rate results from an increase in zinc content
      of the ZnTCP phase in ZnTCP/HAP. The ZnTCP/HAP1.64 would be better than any other
      ZnTCP/HAP relative to material safety because the risk of an accidental burst of
      zinc from the material is minimized due to the low zinc content.

PMID- 12209933
TI  - Novel approach for achieving double-layered cell sheets co-culture: overlaying
      endothelial cell sheets onto monolayer hepatocytes utilizing temperature
      responsive culture dishes.
AB  - Confluent human aortic endothelial cells (HAECs) cultured on thermo-responsive
      culture dish grafted with poly (N-isopropylacrylamide) were recovered as a
      contiguous cell sheet. The double-layered co-culture was achieved by placing the
      recovered HAEC sheet onto the rat hepatocyte layer directly. The double-layered
      structure of HAEC and hepatocytes remained in tight contact during culture.
      Hepatocytes in the layered co-culture system with the HAEC sheet maintained the
      differentiated cell shape and the albumin expression for over 41 days of culture,
      whereas the functions disappeared within 10 days of culture in control
      hepatocytes without the HAEC sheet. The layered co-culture of hepatocytes and the
      HAEC sheets, which allows for the expression of differentiated functions of
      hepatocyte continuously, such as liver lobule, offers a major advancement in
      liver tissue engineering.

PMID- 12209934
TI  - Studies on the tumor promoting mechanism of hard and soft segment models of
      polyetherurethane: Tyr265 phosphorylation of connexin43 is a key step in the GJIC
      inhibitory reaction induced by polyetherurethane.
AB  - Gap junctional intercellular communication (GJIC) is inhibited by 4,4'
      di(ethoxycarboamide) diphenylmethane (MDU) and polytetramethylene oxide 1000
      (PTMO1000), which are model chemicals of hard and soft segments of
      polyetherurethane (PEU), respectively. In our previous study, we suggested that
      the inhibition of GJIC induced by MDU and PTMO1000 may lead to accelerate
      promotion step by both segments after the initiation step by hard segment, MDU.
      To examine this hypothesis, we established connexin 43 overexpressed clones from
      Balb/c 3T3 A31-1-1 clones (A31-1-1 cells) by transfection. Here we show that
      these clones acquired much higher GJIC ability than parental A31-1-1 cells and
      kept them even if MDU or PTMO1000 was added to the culture. We also found that
      Mutation of Cx43 at Tyr-265 resulted in reduced inhibition of GJIC induced by MDU
      and PTMO1000. These findings suggest that inhibition of GJIC by PEU may be caused
      by Tyr-265 phosphorylation of Cx43 molecule.

PMID- 12209935
TI  - Activation of caspase 3 during shear stress-induced neutrophil apoptosis on
      biomaterials.
AB  - Within the complex environment of an implanted cardiovascular device comprised of
      dynamic flow and foreign materials, phagocytic neutrophils may be ineffective in
      combating infection due to cellular responses to shear stress. This may be
      explained, in part, by our recent reports of apoptosis of biomaterial-adherent
      leukocytes induced through exposure to shear stress. Here we utilize a rotating
      disk system to generate physiologically relevant shear stress levels (0-18
      dynes/cm(2)) at the surface of a polyetherurethane urea (PEUU) and investigate
      neutrophil intracellular pathways involved in shear-induced apoptosis. In situ
      detection of activated caspases, the enzymatic mediators of the apoptosis
      cascade, showed qualitatively that these proteases participate in shear-induced
      apoptosis and are activated in a shear-dependent manner. The involvement of
      caspase 3 was confirmed through immunoprecipitation and immunoblotting of
      extracted neutrophil proteins. Comparative studies with neutrophils adherent
      under static conditions demonstrated time-dependent activation of caspases in TNF
      alpha/cycloheximide-induced apoptosis, for which caspase-3 also was implicated.
      These findings are the first steps toward elucidation of the mechanisms behind
      the inappropriate induction of apoptosis by adhesion to biomaterials, which may
      contribute to the development and persistence of device-related infections.

PMID- 12209936
TI  - Repair of segmental defects in rabbit humeri with titanium fiber mesh cylinders
      containing recombinant human bone morphogenetic protein-2 (rhBMP-2) and a
      synthetic polymer.
AB  - To develop a new technology that enhances the regeneration potential of bone and
      the repair of large intercalated defects in long bone, recombinant human bone
      morphogenetic protein-2 (BMP-2; 20 microg or 40 microg) was mixed in a polymer
      gel (poly-lactic acid-polyethyleneglycol block copolymer; PLA-PEG; 200 mg) and
      incorporated into titanium fiber-mesh cylinders. Three 5-mm cylinders were placed
      end-to-end to fill a 15-mm defect created in the humeri of adult rabbits and were
      stabilized by an intramedullary rod. In controls, the titanium fiber-mesh
      cylinders were combined with PLA-PEG in the absence of BMP. Six weeks after
      implantation, new bone had formed on the surface of the implant and had bridged
      the defect. All of the defects (5/5) treated by cylinders containing 120 microg
      (40 microg x 3) of BMP were repaired completely. New bone formation was also
      found inside the pores of the cylinders. The defect was not repaired in the
      control animals. These results demonstrate that these new composite implants
      fabricated by combining rhBMP, synthetic degradable polymers and compatible
      biomaterials enhance the regeneration potential of bone. Thus, it is possible
      that large skeletal defects can be repaired using this prosthesis in lieu of
      autogenous bone graft.

PMID- 12209937
TI  - Mechanisms of magnesium-stimulated adhesion of osteoblastic cells to commonly
      used orthopaedic implants.
AB  - Poor cell adhesion to orthopaedic and dental implants may result in implant
      failure. Cellular adhesion to biomaterial surfaces primarily is mediated by
      integrins, which act as signal transduction and adhesion proteins. Because
      integrin function depends on divalent cations, we investigated the effect of
      magnesium ions modified bioceramic substrata (Al(2)O(3)-Mg(2+)) on human bone
      derived cell (HBDC) adhesion, integrin expression, and activation of
      intracellular signalling molecules. Immunohistochemistry, flow cytometry, cell
      adhesion, cell adhesion blocking, and Western blotting assays were used. Our
      findings demonstrated that adhesion of HBDC to Al(2)O(3)-Mg(2+) was increased
      compared to on the Mg(2+)-free Al(2)O(3). Furthermore, HBDC adhesion decreased
      significantly when the fibronectin receptor alpha5beta1- and beta1-integrins were
      blocked by functional blocking antibodies. HBDC grown on the Mg(2+)-modified
      bioceramic expressed significantly enhanced levels of beta1-, alpha5beta1-, and
      alpha3beta1-integrins receptors compared to those grown on the native unmodified
      Al(2)O(3). Tyrosine phosphorylation of intracellular integrin-dependent
      signalling proteins as well as the expression of key signalling protein Shc
      isoforms (p46, p52, p66), focal adhesion kinase, and extracellular matrix protein
      collagen type I were significantly enhanced when HBDC were grown on Al(2)O(3)
      Mg(2+) compared to the native Al(2)O(3). We conclude that cell adhesion to
      biomaterial surfaces is probably mediated by alpha5beta1- and beta1-integrin.
      Cation-promoted cell adhesion depends on 5beta1- and beta1-integrins associated
      signal transduction pathways involving the key signalling protein Shc and results
      also in enhanced gene expression of extracellular matrix proteins. Therefore,
      Mg(2+) supplementation of bioceramic substrata may be a promising way to improve
      integration of implants in orthopaedic and dental surgery.

PMID- 12209938
TI  - Loading of collagen-heparan sulfate matrices with bFGF promotes angiogenesis and
      tissue generation in rats.
AB  - The loading of biocompatible matrices with growth factors offers the opportunity
      to induce specific cell behavior. The attachment of heparan sulfate (HS) to these
      matrices may promote the binding, modulation, and sustained release of signaling
      molecules. In this study, basic fibroblast growth factor (bFGF) was bound to
      crosslinked collagenous matrices with and without covalently attached HS. The
      tissue response to these matrices was evaluated after subcutaneous implantation
      in rats. Attachment of HS to collagen matrices increased the bFGF binding
      capacity threefold and resulted in a more gradual and sustained release of the
      growth factor in vitro. bFGF primarily was located at the matrix margins. In
      vivo, the presence of HS without bFGF resulted in a transient vascularization,
      predominantly at the matrix periphery. Angiogenesis was further enhanced by
      combining HS with bFGF. In contrast to collagen-HS and collagen/bFGF matrices,
      collagen-HS/bFGF matrices remained highly vascularized throughout the matrix
      during the 10-week implantation period. In addition, these latter matrices
      revealed an intense and prolonged tissue response and considerably promoted the
      generation of new tissue. Foreign body reactions were only observed sporadically
      at this time interval. It is concluded that bFGF loading of collagen-HS matrices
      has additional value for those tissue-engineering applications that require
      enhanced angiogenesis and generation of new tissue.

PMID- 12209939
TI  - Genetic synthesis and characterization of pH- and temperature-sensitive silk
      elastinlike protein block copolymers.
AB  - The purpose of this work was to synthesize and characterize a pH- and temperature
      sensitive block copolymer containing repeating sequences from silk (Gly-Ala-Gly
      Ala-Gly-Ser) and elastin (Gly-Val-Gly-Val-Pro) protein. The monomer contained one
      repeat of silk and eight repeat units of elastin, with the first valine in one of
      the elastin repeats being replaced by glutamic acid. The copolymer was
      synthesized using genetic engineering techniques. The sensitivity of the
      copolymer to pH and temperature was examined at various polymer concentrations
      and ionic strengths. Turbidity measurements were carried out over a temperature
      range of 20 to 100 degrees C at various pH, concentration, and ionic strength
      values. The introduction of an ionizable residue (glutamic acid) rendered the
      copolymer sensitive to changes in pH. The transition termperature (T(t)), the
      temperature at which the polymer became insoluble upon increase in temperature,
      was modulated by changing the pH. In general, the T(t) value, was found: (1) to
      increase with an increase in pH, (2) to decrease with increasing ionic strength,
      and (3) to decrease with increasing concentration. Results of these studies
      suggest that by strategic placement of charged amino acids in genetically
      engineered silk-elastinlike protein block copolymers it is possible to precisely
      control sensitivity to stimuli such as pH and temperature.

PMID- 12209940
TI  - Response of normal female human osteoblasts (NHOst) to 17beta-estradiol is
      modulated by implant surface morphology.
AB  - Titanium (Ti) surfaces with rough microtopographies enhance osteogenic
      differentiation, local factor production, and response to osteogenic agents in
      vitro and increase pullout strength of dental implants in vivo. Estrogens
      regulate bone formation, resorption, and remodeling in females and may be
      important in implant success. Here, we tested the hypothesis that estrogen
      modulates osteoblast response to implant surface morphology. Primary female human
      osteoblasts were cultured to confluence on three Ti surfaces (pretreatment, PT -
      R(a) 0.60 microm; sandblasted and acid-etched, SLA - R(a) 3.97 microm; and Ti
      plasma-sprayed, TPS - R(a) 5.21 microm) and treated for 24 h with 10(-7) or 10(
      8) M 17beta-estradiol (E(2)). Cell number decreased with increasing surface
      roughness, but was not sensitive to E(2). Alkaline phosphatase specific activity
      of isolated cells and cell layer lysates was lower on rough surfaces. E(2)
      increased both parameters on smooth surfaces, whereas on rough surfaces, the
      stimulatory effect of E(2) on alkaline phosphatase was evident only when
      measuring cell layer lysates. Osteocalcin levels were higher in the conditioned
      media of cells grown on rough surfaces; E(2) had no effect in cultures on the
      plastic surfaces, but increased osteocalcin production on all Ti surfaces. TGF
      beta1 and PGE(2) production was increased on rough surfaces, and E(2) augmented
      this effect in a synergistic manner; on smooth surfaces, there was no change in
      production with E(2). The response of osteoblasts to surface topography was
      modulated by E(2). On smooth surfaces, E(2) affected only alkaline phosphatase,
      but on rough surfaces, E(2) increased levels of osteocalcin, TGF-beta1, and
      PGE(2). These results show that normal adult human female osteoblasts are
      sensitive to surface microtopography and that E(2) can alter this response.

PMID- 12209941
TI  - Thermal property and processability of elastomeric polymer alloy composed of
      segmented polyurethane and phospholipid polymer.
AB  - To develop a thermoplastic elastomer with high blood compatibility, a 2
      methacryloyloxyethyl phosphorylcholine (MPC) polymer was blended with the
      segmented polyurethane (SPU) for preparing the polymer alloy. A tensile strength
      measurement was carried out to evaluate its mechanical strength. The mechanical
      strength of the SPU/MPC polymer alloy is the same as that of the original SPU and
      sufficient for use in medical applications. The thermal properties of the polymer
      alloy were evaluated by differential scanning calorimetry (DSC). The DSC curves
      indicated that the MPC polymer blended into the SPU did not affect the hard
      segment domain of the SPU. The SPU/MPC polymer alloy can be processed by heat
      treatment at 150 degrees C. Even after heat treatment, the SPU/MPC polymer alloy
      showed good mechanical properties, and MPC units were observed on the surface.
      Protein adsorption from human plasma was observed to evaluate the blood
      compatibility of the polymer alloy. The SPU/MPC polymer alloy suppressed protein
      adsorption on the surface before and after the heat treatment. Based on these
      results, it is concluded that the SPU/MPC polymer alloy has an excellent
      potential for application in various medical devices.

PMID- 12209942
TI  - Tissue response to microfibers of different polymers: polyester, polyethylene,
      polylactic acid, and polyurethane.
AB  - Tissue response to single polymer microfibers of polyester (PET), polyethylene
      (PE), poly(L-lactic acid) (PLA), and polyurethane (PU) was assessed using a rat
      subcutaneous model. Fibers of diameters ranging from 1 to 15 microm were aligned
      parallel to each other on polycarbonate frames and implanted in the subcutaneous
      dorsum in the subscapular region. After 5 weeks of implantation, fibrous capsule
      thickness was significantly less for fibers of diameters 1-5 than for those of 11
      15 microm for all polymers tested. For PET and PU, 75.0 and 71.4% respectively of
      the 1-5 microm fibers had no capsule, while for PE and PLA only 45.5 and 56.3%
      respectively had no capsule. For 1-5 microm fibers, PE had significantly thicker
      capsules than PET and PU. Reducing fiber diameters from 6-10 to 1-5 microm
      induced a greater reduction in capsule thickness than changing polymers among
      PET, PE, and PLA. PU showed the least encapsulation of all polymers,
      demonstrating significantly thinner capsules than PET, PE, and PLA for 6-10 and
      11-15 microm fibers.

PMID- 12209943
TI  - Surface characteristics and dissolution behavior of plasma-sprayed hydroxyapatite
      coating.
AB  - One of the most important concerns with the clinical use of plasma-sprayed
      hydroxyapatite (HA) coatings is the resorption of the coating, and dissolution at
      neutral pH is one of the two major resorption mechanisms. In this study, highly
      crystalline pure HA powders were atmospherically plasma sprayed using various
      parameters. Dissolution of both HA powders and coatings was measured using a
      calcium ion meter. Surface characteristics, including phase, morphology, and
      roughness, were compared for the coatings before and after dissolution.
      Pulverized HA coatings exhibited significantly higher dissolution compared with
      the same quantity of feedstock HA powders because of the decreased crystallinity
      and fine crystal size of the coating. Furthermore, the dissolution decreased with
      the crystallinity of the coating. Dissolution of HA coatings did not show much
      difference with respect to the coatings in the initial stage of immersion (4 h).
      However, dissolution of all coatings reached saturation in a fresh physiological
      solution. The saturation values were much lower compared with their counterparts
      in the form of powders, which may imply the stability of HA coatings in long-term
      use. In addition to crystallinity, the particle melting status in the coatings,
      i.e., the volume of nanocrystals, and porosity, was found to be another important
      factor for the dissolution of the HA coating. X-ray diffraction patterns of HA
      coatings indicated the complete dissolution of impurity phases and amorphous
      phase after the coatings were immersed in the solution for 4 days. Coatings
      sprayed at lower power (27.5 kW) exhibited a pattern of crystalline HA whereas
      coatings sprayed at higher power (42 kW) exhibited a pattern of bone apatite.
      Surface morphologies showed preferential dissolution of amorphous phase in all
      coatings accompanied with precipitation of bone apatite observable for coatings
      sprayed at higher power. Surface roughness measured after the dissolution studies
      increased for the two coatings sprayed at lower power level but decreased for
      coatings sprayed at higher power level. This decrease is attributed to the better
      match in solubility characteristics between the fine crystals and the amorphous
      calcium phosphate within the coating.

PMID- 12209944
TI  - Low-dose, long-term exposures of dental material components alter human monocyte
      metabolism.
AB  - The short-term degradation of dental polymers and alloys in biological
      environments has been well documented, but recent evidence indicates that oral
      tissues may be chronically exposed to low levels of these released components.
      The effect of these chronic exposures on the ability of cells to respond to a
      subsequent challenge is not known. To investigate this idea, we exposed human THP
      1 monocytes to sublethal concentrations of HEMA, TEGDMA, Hg(2+), and Ni(2+) for 2
      weeks and then assessed the monocytic response to subsequent 24-h challenge with
      the same components at higher concentrations. Chronic (2 week) exposures of
      monocytes to HEMA and both metal ions significantly altered monocyte response to
      short-term (24 h) secondary exposures, even when overt effects of the chronic
      exposures were not apparent. However, cellular responses were highly variable
      depending on the material and its concentrations. For TEGDMA, no effects were
      seen. These results demonstrate that the chronic effects of materials must be
      considered even when the chronic exposure has no initial overt effect. The effect
      on cells may only be apparent if the cell is challenged by a secondary exposure.

PMID- 12209946
TI  - Interaction of fibrinogen with surfaces of end-group-modified polyurethanes: a
      surface-specific sum-frequency-generation vibrational spectroscopy study.
AB  - Fibrinogen adsorption on polyurethanes with different surface-modifying end
      groups (SMEs) has been studied with sum-frequency-generation vibrational
      spectroscopy (SFG). The results show very different protein adsorption properties
      for different SMEs on the same backbone polymer. Fibrinogen binds weakly on the
      hydrophilic backbone of a poly(dimethyl siloxane) (PDMS)-modified polyurethane
      surface but leaves the hydrophobic PDMS part untouched. On sulfonate end-group
      modified (SO(3(-) )) polyurethane surfaces, fibrinogen adsorbs well. However, on
      poly(ethylene oxide) (PEO)-modified surfaces, it adsorbs poorly. The protein
      resistant character of PEO is probably due to steric repulsion. This work
      demonstrates the utility of SFG in the study of protein adsorption on polymeric
      biomaterials at the molecular level and the ability of SMEs to mediate protein
      adsorption.

PMID- 12209945
TI  - Novel graft PLLA-based copolymers: potential of their application to particle
      technology.
AB  - This study describes the synthesis of novel biodegradable graft copolymers based
      on a backbone of poly (L-lactic acid) (PLLA) on which short blocks of
      polyacrylamide (PAcr) were grafted. Preliminary results of their potential in the
      field of controlled-release technologies also have been reported. The copolymers
      have been synthesized through the radical polymerization of acrylamide initiated
      by a peroxide in the presence of PLLA. Two different methodologies of synthesis,
      namely, in solution and in emulsion, have been tested. The structure of the
      copolymers was studied by (1)H-NMR and infrared spectroscopy and by differential
      scanning calorimetry (DSC) and cytotoxicity tests were conducted to assess their
      biocompatibility. The copolymers were used to prepare particles by the emulsion
      solvent evaporation technique. The shapes and dimensions of the particles were
      dependent on the polymer type and concentration used. The surfaces of the
      particles were modified by the presence of polyacrylamide residues, as
      demonstrated by zeta-potential measurements. The release behavior of the
      particles was assessed by encapsulating rhodamine B as the model compound. The
      release was faster for the particles prepared by the grafted polymer as a
      consequence of its increased hydrophilicity. Based on these novel biomaterials,
      preliminary results suggest a potential of the particles for peroral or
      parenteral drug delivery.

PMID- 12209947
TI  - In vitro change in mechanical strength of beta-tricalcium phosphate/copolymerized
      poly-L-lactide composites and their application for guided bone regeneration.
AB  - Novel composites of bioactive beta-tricalcium phosphate [Ca(3)(PO(4))(2)] and
      biodegradable copolymerized poly-L-lactide (CPLA) were prepared by a heat
      kneading method. The mechanical and chemical changes of the composites were
      evaluated in vitro by soaking in physiological saline and Dulbecco's phosphate
      buffered saline. When soaked in physiological saline, the 3-point mechanical
      strength decreased rapidly from 60 to 30 MPa in the initial 4 weeks and then
      gradually reached a plateau; the initial decrease in the mechanical strength was
      ascribed to the dissolution of beta-tricalcium phosphate from the surface. The
      mechanical properties evident at 8-12 weeks were sufficient for the composites to
      be used as a biodegradable material for regeneration of bone because the
      hydrolysis of CPLA was inhibited in both physiological saline and phosphate
      buffered saline as a result of a pH-buffering effect. Composite membranes 250
      microm thick were used to regenerate large bone defects in beagle dogs: 10 x 10 x
      10 mm(3) in volume in the mandible and 20 mm in length in the tibia. The
      afflicted areas covered with the composite membranes were almost perfectly filled
      with new bone 12 weeks after the operation, whereas those covered with a CPLA
      membrane or without any membranes were invaded by soft tissue.

PMID- 12209949
TI  - Improvement of the functions of osteoblasts seeded on modified poly(D,L-lactic
      acid) with poly(aspartic acid).
AB  - One of the challenges in the field of tissue engineering is the development of
      biomaterial/cell interactions. For the purposes of the present study, two
      molecular weights of poly(aspartic acid) (PASP) were used to modify poly(D,L
      lactic acid) (PDLLA) films in order to enhance their cell affinity. The
      properties of the PDLLA-modified surfaces and the controls were investigated by
      water contact angle measurement and electron spectroscopy for chemical analysis
      (ESCA). These data reflect the change in the biocompatibility of modified PDLLA
      surfaces. Then rat osteoblasts were seeded onto these modified surfaces and on
      controls to examine their effects on cell adhesion and proliferation. Cell
      morphologies on these surfaces were studied by scanning electron microscopy
      (SEM), and cell viability was evaluated with a MTT assay. In addition,
      differentiated cell function was assessed by measuring alkaline phosphatase (ALP)
      activity. The results suggest that PASP-modified surfaces may enhance the
      interactions between osteoblasts and PDLLA films.

PMID- 12209948
TI  - The chick chorioallantoic membrane as a novel in vivo model for the testing of
      biomaterials.
AB  - Current in vivo models for testing biomaterials are time and labor intensive as
      well as expensive. This article describes a new approach for testing biomaterials
      in vivo using the chorioallantoic membrane (CAM) of the developing chicken
      embryo, as an alternative to the traditional mammalian models. Fertilized chicken
      eggs were incubated for 4 days, at which time a small window was cut in the shell
      of the egg. After 1 week of incubation, the CAM received several test materials,
      including the endotoxin LPS, a cotton thread and a Silastic tubing. One day and 1
      week later, the tissue response to the test materials was assessed using gross,
      histological, and scanning electron microscope evaluations. The inflammatory
      response of the chorioallantoic membrane to biomaterials was fully characterized
      and found to be similar to that of the mammalian response and was also seen to
      vary according to test materials. We also found that the structure and geometry
      of the test materials greatly influenced the incorporation of the samples in the
      CAM. The similarity of the tissue response of the CAM with the mammalian models,
      plus the low cost, simplicity, and possibility to continuously visualize the test
      site through the shell window make this animal model particularly attractive for
      the rapid in vivo screening of biomaterials.

PMID- 12209950
TI  - Enhancement of osteogenesis on hydroxyapatite surface coated with synthetic
      peptide (EEEEEEEPRGDT) in vitro.
AB  - Some dental implants are coated with hydroxyapatite (HA), which preferentially
      binds to bone. Several matrix proteins have an arginine-glycine-aspartic acid
      (RGD) sequence where cells attach via an integrin receptor. We hypothesized that
      coating an HA surface with an RGD-containing peptide might enhance the attachment
      and differentiation of osteoblasts. The HA disks (diameter 34 mm, thickness 1 mm)
      were treated with a solution (50 mM Tris/HCl and 150 mM NaCl, pH 7.4) containing
      the peptide EEEEEEEPRGDT, in which the E repetition exerts a high affinity to HA.
      After washing with phosphate-buffered saline, KUSA/A1 mouse osteoblastic cells
      were inoculated onto the HA surface and cultured. After 30 min, the number of
      cells attached to the surface was counted. The DNA content and alkaline
      phosphatase (ALP) activity were measured after 10 days in culture. Expression of
      bone matrix proteins was also examined by means of reverse transcriptase
      polymerase chain reaction at 7 days; the mineralized area of the culture was also
      evaluated by staining with Alizarin Red S after 10 days. Treatment with the
      peptide stimulated cell attachment and increased DNA content and ALP activity.
      Furthermore, matrix protein expression and mineralized nodule formation were
      enhanced to a greater extent on the peptide-treated surface than on the
      nontreated surface. Our results indicate that coating an HA surface with RGD
      containing peptide enhances osteoblast attachment and differentiation. This
      peptide treatment of HA-coated implants may stimulate the osseointegration of the
      implants.

PMID- 12209951
TI  - New acrylic bone cements conjugated to vitamin E: curing parameters, properties,
      and biocompatibility.
AB  - Acrylic bone cement formulations with antioxidant character were prepared by
      incorporation of a methacrylic monomer derived from vitamin E (MVE). Increasing
      concentrations of this monomer provided decreasing peak temperature values,
      ranging from 62 to 36 degrees C, and increasing setting time with values between
      17 and 25 min. Mechanical properties were evaluated by compression and tension
      tests. Compressive strength of the new formulations were superior to 70 MPa in
      all cases. The cement containing 25 wt % MVE, however, showed a significant
      decrease in tensile properties. Biocompatibility of the new formulations was
      studied in vitro. The analysis of the effect of leachables from cements into the
      media showed continued cell proliferation and cell viability with a significant
      increase for the cement containing 15 wt % MVE. This formulation also showed a
      significant increase in cellular proliferation over a period of 7 days as
      indicated by the Alamar Blue test. The cells were able to differentiate and
      express phenotypical markers in presence of all materials. A significant increase
      in alkaline phosphatase activity was observed on the cements prepared in presence
      of 15-25 wt % MVE compared with PMMA. Morphological assessment showed that the
      human osteoblast (HOB) cells were able to adhere, retain their morphology, and
      proliferate on all the cements.

PMID- 12209952
TI  - In vivo drug distribution dynamics in thermoablated and normal rabbit livers from
      biodegradable polymers.
AB  - Image-guided radiofrequency ablation combined with intratumoral drug delivery
      provides a novel and minimally invasive treatment of liver cancers. In this
      study, the in vivo transport properties of doxorubicin in thermoablated and
      nonablated rabbit livers were characterized and compared. Doxorubicin was
      released from polymer implants (millirods) to the ablated and nonablated liver
      tissue. At different time points, the 2D distribution profiles were
      quantitatively determined by a fluorescence imaging method. Analysis of the
      doxorubicin concentration at the ablation boundary showed that it reached a
      maximum of 49.8 microg/g at 24 h after implantation, which was higher than the
      reported cytotoxic concentration of doxorubicin (6.4 microg/g) for liver VX-2
      cancer cells. This value dropped to 0.4 microg/g at 48 h after implantation due
      to the depletion of doxorubicin from the polymer millirod. Results also showed
      that the area of drug distribution was significantly larger in ablated tissue
      than nonablated tissue. The therapeutic penetration distance was found to be 5.2
      mm in thermoablated livers, compared to 1.2 mm in nonablated livers at 24 h. This
      difference in drug transport properties is attributed to destruction of the
      vasculature network in the ablated tissue as supported by histological analysis.
      Consequently, drug washout by blood perfusion is hampered while drug diffusion
      becomes the dominant process of transport in the ablated tissue. Results from
      this study provide insightful information on the rational design and development
      of polymer millirods for intratumoral drug delivery applications.

PMID- 12209953
TI  - Elevated protein expression of cyclin D1 and Fra-1 but decreased expression of c
      Myc in human colorectal adenocarcinomas overexpressing beta-catenin.
AB  - Mutations of the adenomatous polyposis coli tumor suppressor gene, or its
      downstream target beta-catenin, have been implicated in the initiation of most
      sporadic human colorectal epithelial neoplasms. These mutations, in turn, lead to
      aberrant nuclear accumulation of beta-catenin and subsequent activation of the
      beta-catenin/Tcf transcription factor complex. In vitro studies utilizing
      cultured human colon cancer cell lines have identified c-myc, cyclin D1 and fra-1
      as target genes of beta-catenin/Tcf signaling. In our study, 12 cases of human
      colorectal adenocarcinomas were examined by Western immunoblotting analysis and
      immunohistochemical staining to specifically investigate whether the protein
      expression of these target genes was indeed altered in vivo by beta-catenin
      dysregulation. The results show that the protein level of beta-catenin was
      significantly increased in all 12 tumors (3.4 +/- 1.0-fold increase compared to
      the control normal mucosa by Western immunoblotting, p < 0.05), and this increase
      was associated with positive nuclear staining by immunohistochemistry in 10
      cases. Increased levels of expression of cyclin D1 and Fra-1 proteins were also
      demonstrated in every tumor (9.0 +/- 2.7 and 3.3 +/- 0.9-fold increases compared
      to normal mucosa, respectively). Surprisingly, the protein level of c-Myc was
      significantly decreased in all tumors examined by 49 +/- 19% (p < 0.05), but the
      c-myc mRNA level was increased in 8 of 12 tumors when compared to that in normal
      mucosa by RT-PCR. Immunohistochemical staining performed on these carcinomas and
      additional 27 colorectal carcinomas further demonstrated that the protein
      expression level of c-Myc and beta-catenin nuclear localization were not
      correlated. Moreover, 15 of 20 colorectal adenomas exhibited positive nuclear
      beta-catenin immunostaining, among which 11 also exhibited increased c-Myc
      protein expression. These data thus support the notion that upregulation of
      cyclin D1 and Fra-1 in human colorectal adenocarcinomas is driven by abnormally
      expressed beta-catenin. However, the regulation of c-myc expression in colorectal
      tumors appears to be more complex. While dysregulated beta-catenin may cause a
      transcriptional upregulation of the c-myc gene, the c-Myc protein expression
      appears to be further regulated by a posttranscriptional mechanism(s) during the
      process of neoplastic progression.

PMID- 12209954
TI  - A novel gene, NMES1, downregulated in human esophageal squamous cell carcinoma.
AB  - To isolate genes with different expression levels in human esophageal SCC, SSH
      and reverse Northern were performed between cancer tissue and its normal
      counterpart. Among the differentially expressed genes identified, we report here
      cDNA corresponding to a 0.88 kb mRNA (NMES1), whose expression was observed in
      all 36 adjacent normal esophageal mucosae, while 31 (86%) matched cancer tissues
      showed a marked reduction or complete lack of its expression. Sequence analysis
      of its full-length cDNA revealed a gene encoding a predicted polypeptide of 9
      kDa. Northern blot showed that NMES1 was distributed mainly in the alimentary
      tract. The gene was mapped to 15q21.1 by screening the GenBridge 4 RH panel.
      Immunohistochemistry confirmed the downregulation of NMES1 in esophageal SCC at
      the protein level and showed that it is a nuclear protein. In situ hybridization
      revealed its different expression during mouse embryonic development, especially
      in bone, brain, stomach and intestine. The negative correlation of NMES1
      expression with esophageal oncogenesis suggests its suppressive role in
      tumorigenesis of the esophagus, while the precise function of NMES1 still needs
      further investigation.

PMID- 12209955
TI  - Inhibition of apoptosis in human breast cancer cells: role in tumor progression
      to the metastatic state.
AB  - Reduction in apoptosis has been associated with tumor metastases and response to
      chemotherapy in breast cancer. We examine the influence of apoptosis status and
      the expression of antiapoptotic proteins Bcl-2 and Bcl-x(L) on metastatic
      progression and response to therapy in an experimental model of breast cancer. We
      used human breast cancer cells (MDA-MB 435, MDA-MB 468 and MCF-7) to induce
      orthotopic xenograft tumors in nude mice. The overexpression of Bcl-2 or Bcl-x(L)
      influenced tumorigenicity, 468 transfectants being less tumorigenic than control
      (p < 0.0001). Lung metastasis appeared at day 120 in animals injected with
      435/Bcl-2 or 435/Bcl-x(L) and they showed higher metastatic activity than control
      435/Neo tumors (p = 0.02). In contrast, mice with 468 tumors were followed for 1
      year after tumor excision, but they did not develop metastatic foci. 435/Bcl-2
      and 435/Bcl-x(L) transfectant cells bound less readily to laminin (ANOVA, p <
      0.0001), fibronectin (ANOVA, p < 0.0001) and collagen type-IV (ANOVA, p < 0.0001)
      than 435/Neo cells. The overexpression of antiapoptotic proteins in 435
      transfectants rescued 20-40% of cells from anoikis at 64 hr in rocking
      conditions. In contrast, at this time only 5-10% of 468 and MCF-7 transfectant
      cells were rescued. Thus, the overexpression of the Bcl-2 or Bcl-x(L) associated
      with the loss of apoptosis in breast cancer cells in vivo may account for their
      metastatic behavior. These genes increase tumor metastasis when the oncogenic
      background has triggered the metastatic process, in which anoikis might determine
      tumor progression when the life span of the cells is extended.

PMID- 12209956
TI  - Expression of cadherin-8 in renal cell carcinoma and fetal kidney.
AB  - Cadherins represent a family of calcium-dependent cell adhesion molecules with an
      important regulatory function for maintenance of tissue architecture. Alterations
      of cadherin expression have been demonstrated in the development and progression
      of different epithelial tumors. In renal cell carcinoma (RCC), the majority of
      tumors express N-cadherin and cadherin-6. Screening a series of 16 RCC cell lines
      for the expression of different novel type II cadherins by RT-PCR revealed a
      complex pattern of cadherin expression: cadherins 6 and 14 were expressed in most
      of the RCC cell lines, whereas cadherins 11, 12 and 13 could not be detected at
      all. Interestingly, cadherin-8, previously shown in mice to be restricted to the
      CNS and thymus during development, was detected by RT-PCR, immunofluorescence and
      in situ hybridization in 4 of 16 RCC cell lines as well as in paraffin sections
      of the corresponding human RCC biopsies. In normal renal tissue, however,
      cadherin-8 could be detected only during the early stages of kidney development.
      These results suggest that alterations of type II cadherin expression may play a
      role in RCC development. In particular, cadherin-8 may be involved in both kidney
      morphogenesis as well as tumorigenesis in some types of RCC.

PMID- 12209957
TI  - Hypermethylation of the human telomerase catalytic subunit (hTERT) gene
      correlates with telomerase activity.
AB  - DNA methylation is an epigenetic process involved in embryonic development,
      differentiation and aging. It is 1 of the mechanisms resulting in gene silencing
      in carcinogenesis, especially in tumor suppressor genes (e.g., p16, Rb).
      Telomerase, the DNA polymerase adding TTAGGG repeats to the chromosome end, is
      involved in the regulation of the replicative life span by maintaining telomere
      length. This enzyme is activated in germ and stem cells, repressed in normal
      somatic cells and reactivated in a large majority of tumor cells. The promoter
      region of the hTERT gene, encoding for the catalytic subunit of human telomerase,
      has been located in a CpG island and may therefore be regulated at least in part
      by DNA methylation. We analyzed the methylation status of 27 CpG sites within the
      hTERT promoter core region by methylation-sensitive single-strand conformation
      analysis (MS-SSCA) and direct sequencing using bisulfite-modified DNA in 56 human
      tumor cell lines, as well as tumor and normal tissues from different organs. A
      positive correlation was observed among hypermethylation of the hTERT promoter,
      hTERT mRNA expression and telomerase activity (p < 0.00001). Furthermore, this
      correlation was confirmed in normal tissues where hypermethylation of the hTERT
      promoter was found exclusively in hTERT-expressing telomerase-positive samples
      and was absent in telomerase-negative samples (p < 0.00002). Since tumor tissues
      contain also nonneoplastic stromal elements, we performed microdissection to
      allow confirmation that the hTERT promoter methylation truly occurred in tumor
      cells. Our results suggest that methylation may be involved in the regulation of
      hTERT gene expression. To our knowledge, this is the first gene in which
      methylation of its promoter sequence has been found to be positively correlated
      with gene expression.

PMID- 12209958
TI  - Gene expression analysis of human thymoma correlates with tumor stage.
AB  - Thymoma is one of the most common solid tumors in the mediastinum. The recent
      development of high-density oligonucleotide arrays provides a unique opportunity
      to generate gene expression profiles of cells from various stages of tumor
      progression as it occurs in actual neoplastic tissues. We used oligonucleotide
      arrays to monitor in vivo gene expression levels in early- (stage I or II) and
      late- (stage IVa) stage thymoma tissues in 36 patients. These in vivo gene
      expression profiles were verified by real-time quantitative RT-PCR using
      LightCycler. Using both methods, 2 candidate genes were identified that were more
      highly expressed in advanced-stage thymomas. One was a well-known gene, c-JUN,
      and another was an unknown gene, AL050002. AL050002 expression, but not c-JUN
      expression, was also correlated with the WHO classification (type B3 vs. type B1,
      B2 or AB). The combined use of oligonucleotide microarray and real-time RT-PCR
      analyses provides a powerful new approach to elucidate the in vivo molecular
      events correlated with tumor stage of thymoma.

PMID- 12209959
TI  - Absence of simian virus 40 in human brain tumors from northern India.
AB  - Simian virus 40 (SV40), a monkey polyomavirus, was a contaminant of early
      poliovirus vaccines administered to millions of individuals in the 1950s and
      early 1960s. SV40 causes brain tumors in laboratory animals, and SV40 DNA
      sequences have been variably identified in human choroid plexus tumors and
      ependymomas. We studied the possible association between SV40 and human brain
      tumors in northern India, where humans have frequent contact with SV40-infected
      rhesus macaques. DNA from pathologic specimens from 33 ependymomas, 14 choroid
      plexus tumors and 18 control brain tissues (contused brain, brain metastases) was
      extracted and analyzed under masked conditions. We used real-time PCR to detect
      and quantify SV40 (T antigen) and human (GAPDH) DNA sequences. The SV40 PCR assay
      detected as few as 10 copies of SV40 DNA and had a linear range from 1 x 10(2) to
      1 x 10(6) copies. SV40 DNA was detected in 1 specimen (an ependymoma). However,
      few SV40 DNA copies were detected in this sample (<10 copies, equivalent to <1
      copy/350 cells, based on simultaneous GAPDH quantification), and SV40 was not
      detected when this sample was retested. Our findings do not support a role for
      SV40 in choroid plexus tumors or ependymomas from northern India.

PMID- 12209960
TI  - Presentation of native TROP-2 tumor antigens to human cytotoxic T lymphocytes by
      engineered antigen-presenting cells.
AB  - Professional antigen-presenting cells (APC), e.g. dendritic cells, express immuno
      proteasome components and process proteins for MHC presentation differently from
      non-immune cells. Thus, they induce reactivities against sets of peptides that do
      not overlap with those generated by non-professional APC, i.e., tumor cells, and
      stimulate cytotoxic T lymphocytes (CTL) that may not recognize them. The goal of
      this work was to establish a system for antigen presentation and in vitro
      stimulation of human CTL using "tumor-cell-like" engineered APC. Murine
      fibroblasts were transfected with human HLA Class I alleles, together with the
      B7.1, ICAM-1 and germ-line TROP2 genes. The last encodes a cell surface
      glycoprotein widely expressed by human cancers. Unseparated peripheral blood
      mononuclear cells from HLA Class I-matched individuals were stimulated in vitro
      by the engineered APC. These efficiently induced the activation and proliferation
      of antigen-specific HLA-restricted CTL lines and clones. The Trop-2-specific CTL
      demonstrated high specific cytotoxicity against the appropriate transfected
      target cells. They also efficiently lysed MCF-7 human tumor cells expressing
      endogenous HLA-A2.1, Trop-2 together with ICAM-1. These results demonstrate that
      Trop-2 is a target molecule recognized by human CTL. Moreover, they demonstrate
      that non-immune engineered APC efficiently process and present native tumor
      specific proteins in the context of human MHC Class I, and stimulate the growth
      and cytotoxicity of specific anti-tumor CTL.

PMID- 12209961
TI  - Labeled EGFr-TK irreversible inhibitor (ML03): in vitro and in vivo properties,
      potential as PET biomarker for cancer and feasibility as anticancer drug.
AB  - Radiosynthesis of ML03 (N-[4-[(4,5-dichloro-2-fluorophenyl)amino]quinazolin-6
      yl]acrylamide), an irreversible EGFr-TK inhibitor, was developed. Its in vitro
      and in vivo properties, its potential as PET biomarker in cancer and the
      feasibility of this type of compounds to be used as anticancer drug agents were
      evaluated. The compound was labeled with carbon-11 at the acryloyl amide group,
      via automated method with high yield, chemical and radiochemical purities. ELISA
      carried out with A431 lysate showed high potency of ML03 with an apparent IC(50)
      of 0.037 nM. The irreversible binding nature of ML03 was studied and 97.5% EGFr
      TK autophosphorylation inhibition was observed in intact A431 cells 8 hr post
      incubation with the inhibitor. Specific binding (67%) of [(11)C]ML03 was obtained
      in cells. An A431 tumor-bearing rat model was developed and the validity of the
      model was tested. In biodistribution studies carried out with tumor-bearing rats,
      moderate uptake was observed in tumor and high uptake in liver, kidney and
      intestine. In metabolic studies, fast degradation of [(11)C]ML03 was observed in
      liver and blood indicating a short half-life of the compound in the body. PET
      scan with tumor-bearing rats confirmed the results obtained in the ex vivo
      biodistribution studies. Although in vitro experiments may indicate efficacy of
      ML03, non-specific binding, ligand delivery and degradation in vivo make ML03
      ineffective as PET bioprobe. Derivatives of ML03 with lower metabolic clearance
      rate and higher bioavailability should be synthesized and their potential as
      anticancer drugs and PET bioprobes evaluated.

PMID- 12209962
TI  - A population-based prospective study of Chlamydia trachomatis infection and
      cervical carcinoma.
AB  - Persistent human papillomavirus (HPV) infection is an established cause of
      cervical cancer, but the role of other sexually transmitted agents, most notably
      Chlamydia trachomatis, has not been well defined. The women participating in the
      population-based cervical cancer screening program in Vasterbotten county of
      Northern Sweden were followed up for up to 26 years to identify 118 women who
      developed cervical cancer after having had a normal Pap smear (on average 5.6
      years later; range 0.5 months-26 years). As controls, we selected another 118
      women who were matched by birth cohort, time-point of sampling of the baseline
      normal smear and who had a normal smear at the time when the corresponding case
      was diagnosed with cancer. The Pap smears and cervical cancer biopsies were
      analyzed by PCR for C. trachomatis DNA and for HPV DNA. At baseline, C.
      trachomatis DNA was present in 8% of cases but not among any one of the controls.
      The relative risk for cervical cancer associated with past C. trachomatis
      infection, adjusted for concomitant HPV DNA positivity, was 17.1 (95% CI 2.6
      infinity). The presence of C. trachomatis and of HPV were not interrelated.
      Whereas C. trachomatis was primarily found in specimens taken many years before
      cancer diagnosis, HPV DNA was associated with a short lag time before cancer
      diagnosis. Whereas most women who were HPV DNA-positive in the prediagnostic
      smear were also positive for the same virus in the cervical cancer biopsy, none
      of the women were positive for C. trachomatis in both the prediagnostic smear and
      in the subsequent cervical cancer. In conclusion, a prior cervical C. trachomatis
      infection was associated with an increased risk for development of invasive
      cervical cancer.

PMID- 12209963
TI  - The density of melanocytic nevi correlates with constitutional variables and
      history of sunburns: a prevalence study among Italian schoolchildren.
AB  - In several studies from northern Europe, north America and Australia, melanocytic
      nevi are correlated with pigmentary traits and with intense sun exposure in a way
      similar to malignant melanoma. However, it is unclear if these data can be
      extrapolated to populations in other geographic locations and with different
      prevalent phenotypes. Our study was conducted among schoolchildren aged 13-14
      years in 16 Italian cities. The parents of 3,127 children of a total of 3,160
      (99%) consented to our study. A structured questionnaire was used to collect
      information about sun exposure and lifetime history of sunburns. Children were
      also examined by trained dermatologists to assess pigmentary traits and to make a
      count of melanocytic nevi. The median nevus density was higher among boys than
      girls. Areas that are usually chronically exposed to the sun exhibited a higher
      density of nevi compared to intermittently and rarely exposed areas. A higher
      density of nevi was found in children with lighter skin, blond hair and blue
      eyes. Red-haired children had a remarkably lower nevus density compared to the
      other color categories. The density of nevi increased with an increased number of
      reported episodes of sunburns. The results concerning nevi >/=6 mm in diameter
      paralleled those obtained for the total nevus density. However, at variance with
      total nevus density, a significant relation was also observed between larger nevi
      and freckling. Our study confirms that, in Italian schoolchildren, there is a
      relation between pigmentary traits, history of sunburns and the density of
      melanocytic nevi. Melanocytic nevi and malignant melanoma share a similar risk
      factor profile.

PMID- 12209964
TI  - Cigarette smoking, use of other tobacco products and stomach cancer mortality in
      US adults: The Cancer Prevention Study II.
AB  - Cigarette smoking is associated with increased risk of stomach cancer in many
      studies but there are limited data on this relationship in women and on risk
      associated with use of tobacco products other than cigarettes. We examined
      stomach cancer death rates in relation to cigarette smoking in women and use of
      cigarette, cigar, pipe, or smokeless tobacco in men in a nationwide prospective
      mortality study in the United States (US). Cohort follow-up from 1982-96
      identified 996 and 509 stomach cancer deaths among 467,788 men and 588,053 women,
      respectively. Cox proportional hazards models were fitted to estimate rate ratios
      (RR) and 95% confidence intervals (CI) using non-users of tobacco as the referent
      group. Multivariate-adjusted RRs were the highest for men who currently smoked
      cigars (RR = 2.29, 95% CI = 1.49-3.51) or cigarettes (RR = 2.16, 95% CI = 1.75
      2.67) and both increased with smoking duration. Women who currently (RR = 1.49,
      95% CI = 1.18-1.88) or formerly (RR = 1.36, 95% CI = 1.08-1.71) smoked cigarettes
      were at significantly increased risk, as were men who formerly smoked cigarettes
      (RR = 1.55, 95% CI = 1.28-1.88), or currently (RR = 1.81, 95% CI = 1.40-2.35) or
      formerly (RR: 1.57, 95% CI = 1.22-2.03) used more than one type of tobacco. Men
      who reported a history of chronic indigestion or gastroduodenal ulcer had
      substantially higher mortality rates associated with current cigarette (RR =
      3.45, 95% CI = 2.05-5.80) or cigar (RR = 8.93, 95% CI = 4.02-19.90) smoking, as
      did men who were current aspirin users. If causal, the estimated proportion of
      stomach cancer deaths attributable to tobacco use would be 28% in US men and 14%
      in women. We conclude that prolonged use of tobacco products is associated with
      increased stomach cancer mortality in men and women. The accumulated evidence
      from this and other studies support reconsidering stomach cancer as a tobacco
      related cancer.

PMID- 12209965
TI  - Anti-epidermal growth factor receptor-antibody therapy for treatment of breast
      cancer.
AB  - Recent studies demonstrated that tumors overexpressing the epidermal growth
      factor receptor (EGF-R, erbB-1) are associated with poor clinical outcome. This
      led to the development of a variety of monoclonal antibodies targeting the
      extracellular domain of this receptor tyrosine kinase. The aim of our study was
      the evaluation of anti-EGF-R antibody EMD 55900 therapy for treatment of breast
      cancer. On the basis of 299 tumor specimens derived from breast cancer patients,
      we investigated EGF-R expression and generated a collective of primary
      xenotransplants in athymic nude mice. The animals received therapy in 2 treatment
      schedules to investigate the therapeutic response in early stages of tumor
      formation as well as on well established tumors. Using 6 different tumors with
      EGF-R expression levels between 10-300 fmol/mg total protein, we found a
      therapeutic effect when the EGF-R expression of the tumors was at least 40
      fMol/mg. On the basis of these experimental data and our EGF-R expression
      analysis of breast cancer specimens, we conclude that up to 15% of breast cancer
      patients could benefit from this monotherapy with EMD 55900.

PMID- 12209966
TI  - Persistent oxidative stress in colorectal carcinoma patients.
AB  - We examine whether the level of 8-oxo-2'-deoxyguanosine (8-oxodGuo) in
      lymphocytes DNA is higher in colon cancer when compared to the control group.
      Factors that may influence oxidative stress such as antioxidant vitamins and uric
      acid were also determined. Blood samples were obtained from a control group of 55
      healthy persons and 43 colon cancers. 8-OxodGuo level and the vitamins
      concentration were measured by high-performance liquid chromatography. The levels
      of 8-oxodGuo were significantly higher whereas the concentrations of the vitamins
      and uric acid were significantly lower in colon cancer patients than in control
      group. Therefore, the decreased concentration of antioxidant vitamins together
      with lower amount of uric acid may be responsible for the formation of pro
      oxidative environment in blood of colorectal carcinoma patients.

PMID- 12209967
TI  - Lack of beta-tubulin gene mutations in early stage lung cancer.

PMID- 12209969
TI  - Impact of genomic instability in risk assessment and chemoprevention of oral
      premalignancies.
AB  - Head-and-neck cancer is a disfiguring disease with increasing incidence rates
      even in young people, whose exposure to known risk factors is limited. This
      emphasizes the importance of early identification, on an individual basis, of
      precursor lesions that will develop into carcinomas. The clinical value of
      identifying individuals at high risk of oral cancer is emphasized by the fact
      that these patients are likely to benefit from available chemopreventive
      measures, largely without adverse effects.

PMID- 12209970
TI  - Meta-iodobenzylguanidine induces growth inhibition and apoptosis of
      neuroendocrine gastrointestinal tumor cells.
AB  - Neuroendocrine gastrointestinal tumors take up, decarboxylate and store large
      amounts of monoamines. Radioactive-labeled monoamines like the norepinephrine
      analogue meta-iodobenzylguanidine (MIBG) have been used for the imaging of
      neuroendocrine tumors for many years. MIBG is selectively taken up via
      norepinephrine transporters (NETs) localized in the plasma membrane of
      neuroendocrine gastrointestinal tumor cells and thereby offers the possibility
      for specific and innovative therapeutic approaches. We investigated the
      antiproliferative, cytotoxic, cell cycle-arresting and apoptosis-inducing effects
      of MIBG in the neuroendocrine gastrointestinal tumor cell line STC-1 and for
      control in the nonneuroendocrine colorectal cancer cell line HT-29. RT-PCR
      revealed the expression of NET in STC-1 but not in HT-29 cells. MIBG dose
      dependently induced cytotoxicity and growth inhibition of STC-1 cells. It
      potently induced apoptosis in STC-1 cells as assessed by changes in the
      mitochondrial membrane potential, activation of caspase-3 and DNA fragmentation.
      Moreover, MIBG altered the expression of several genes involved in proliferation,
      apoptosis and stress responses as shown by cDNA arrays. In contrast, neither
      cytotoxicity, nor growth inhibition nor induction of apoptosis were detected in
      response to MIBG in the NET-deficient colorectal cancer cell line HT-29. Our data
      show that MIBG induces growth inhibition and apoptosis in neuroendocrine
      gastrointestinal tumor cells. MIBG did not arrest the cell cycle in either cell
      line. Thus, monoamine transporters in the plasma membrane of neuroendocrine
      gastrointestinal tumor cells are promising targets for innovative and specific
      treatment strategies of these tumors.

PMID- 12209971
TI  - Autocrine motility factor secreted by tumor cells upregulates vascular
      endothelial growth factor receptor (Flt-1) expression in endothelial cells.
AB  - The autocrine motility factor (AMF) is known as a cytokine regulating tumor cells
      motility via AMF receptor (AMFR) and promotes their metastasis. Recently, AMFRs
      have been found on the surface of host cells and it was showed that AMF possibly
      affects them. The signaling of AMF-AMFR in the host endothelial cells induces
      expression of a vascular endothelial growth factor receptor (VEGFR) Flt-1 and
      AMFR feedback that is regulated at the transcriptional level. AMF-exposure
      stimulated the Flt-1 expression on human umbilical vein endothelial cells
      (HUVECs) surface and this AMF-treated cells exhibited high-responsibility against
      VEGF. The protein kinase C (PKC) and phosphatidylinositol 3 kinase (PI3K) play an
      important role in this signal transduction. The findings of our study suggest the
      possibility of "tumor AMF-->host AMFR-->PKC, PI3K-->-->VEGFR or AMFR-
      >angiogenesis, metastasis" as a new signal cross talk between the tumor and the
      host.

PMID- 12209972
TI  - Inhibition of the mammary carcinoma angiogenic switch in C3(1)/SV40 transgenic
      mice by a mutated form of human endostatin.
AB  - Cancer therapies based on the inhibition of angiogenesis by endostatin have
      recently been developed. We demonstrate that a mutated form of human endostatin
      (P125A) can inhibit the angiogenic switch in the C3(1)/Tag mammary cancer model.
      P125A has a stronger growth-inhibitory effect on endothelial cell proliferation
      than wild-type endostatin. We characterize the angiogenic switch, which occurs
      during the transition from preinvasive lesions to invasive carcinoma in this
      model, and which is accompanied by a significant increase in total protein levels
      of vascular endothelial growth factor (VEGF) and an invasion of blood vessels.
      Expression of the VEGF(188) mRNA isoform, however, is suppressed in invasive
      carcinomas. The VEGF receptors fetal liver kinase-1 (Flk-1) and Fms-like tyrosine
      kinase-1 (Flt-1) become highly expressed in epithelial tumor and endothelial
      cells in the mammary carcinomas, suggesting a potential autocrine effect for VEGF
      on tumor cell growth. Angiopoietin-2 mRNA levels are also increased during tumor
      progression. CD-31 (platelet-endothelial cell adhesion molecule [PECAM]) staining
      revealed that blood vessels developed in tumors larger than 1 mm The
      administration of P125A human endostatin in C3(1)/Tag females resulted in a
      significant delay in tumor onset, decreased tumor multiplicity and tumor burden
      and prolonged survival of the animals. Endostatin treatment did not reduce the
      number of preinvasive lesions, proliferation rates or apoptotic index, compared
      with controls. However, mRNA levels of a variety of proangiogenic factors (VEGF,
      VEGF receptors Flk-1 and Flt-1, angiopoietin-2, Tie-1, cadherin-5 and PECAM) were
      significantly decreased in the endostatin-treated group compared with controls.
      These results demonstrate that P125A endostatin inhibits the angiogenic switch
      during mammary gland adenocarcinoma tumor progression in the C3(1)/Tag transgenic
      model.

PMID- 12209973
TI  - Monensin-mediated growth inhibition in acute myelogenous leukemia cells via cell
      cycle arrest and apoptosis.
AB  - Monensin, an Na(+) ionophore, regulates many cellular functions including
      apoptosis. However, there has been no report about the antitumoral effect of
      monensin on acute myelogenous leukemia (AML). Here, we investigated the
      antiproliferative effect of monensin on AML cells in vitro and in vivo. Monensin
      efficiently inhibited the proliferation of all of 10 AML cell lines, with IC(50)
      of about 0.5 microM. DNA flow cytometric analysis indicated that monensin induced
      a G(1) and/or a G(2)-M phase arrest in these cell lines. To address the mechanism
      of the antiproliferative effect of monensin, we examined the effect of monensin
      on cell cycle-related proteins in HL-60 cells. The levels of CDK6, cyclin D1 and
      cyclin A were decreased. In addition, monensin not only increased the p27 level
      but also enhanced its binding with CDK2. Furthermore, the activities of CDK2- and
      CDK6-associated kinases reduced by monensin were associated with
      hypophosphorylation of Rb protein. Monensin also induced apoptosis in AML cells
      including HL-60 cells. The apoptotic process of HL-60 cells was associated with
      changes in Bax, caspase-3, caspase-8 and mitochondria transmembrane potential
      (Deltapsi(m)). In particular, monensin (i.p. at a dose of 8 mg/kg thrice weekly)
      significantly reduced the tumor size of BALB/c mice that were inoculated s.c.
      with its derived cell line, WEHI-3BD cells (69% growth inhibition relative to
      control group; p < 0.05). Tumors from monensin-treated mice exhibited increased
      apoptosis, and these tumor were immunohistochemically more stained with Bax, Fas
      and p53 antibodies than control tumors. In conclusion, this is the first report
      that monensin potently inhibits the proliferation of AML cells.

PMID- 12209974
TI  - Cyclosporin A enhances the apoptotic effects of N-(4-hydroxyphenyl)retinamide in
      breast cancer cells.
AB  - 4HPR, an analogue of ATRA, effectively induces growth inhibition and apoptosis in
      breast cancer cell lines and animal models but is ineffective against advanced
      human breast tumors. Different compounds, including tamoxifen, are currently
      being tested to increase 4HPR efficacy in the clinic. Here, we report that
      cyclosporin A selectively increases the ability of 4HPR, but not ATRA, to induce
      growth inhibition and apoptosis in ER(+) and ER(-) breast cancer cell lines.
      Increased apoptosis by the 4HPR and cyclosporin A combination was correlated with
      increased production of the free radical nitric oxide. Thus, the 4HPR and
      cyclosporin A combination may potentially be a novel therapeutic modality against
      breast tumors.

PMID- 12209975
TI  - p53 status correlates with the differential expression of the DNA mismatch repair
      protein MSH2 in non-small cell lung carcinoma.
AB  - We examined the p53 status of 108 NSCLCs compared to the expression of MLH1 and
      MSH2 proteins. p53 overexpression was demonstrated by IHC in 64% of patients
      examined, whereas p53 mutations were detected in 43%. Twenty-two percent of
      mutations were located outside of the hot-spot (exons 5-8) area. p53 mutations
      and overexpression were more frequent in SCCL (57% and 73%, respectively) than in
      lung adenocarcinomas (22% and 50%, respectively). In NSCLC-carrying wild-type
      p53, increased expression of MSH2 correlated with p53 overexpression (p = 0.018).
      In addition, in SCCL, p53 mutations correlated with reduced MSH2 expression (p =
      0.019). These data suggest a relationship between p53 and MSH2. While there is
      evidence for p53 being a transcriptional activator of MSH2, the hypothesis that
      MSH2 acts as a DNA-damage signaller triggering p53 overexpression needs to be
      clarified in future studies.

PMID- 12209976
TI  - Increased risk of grade IV neutropenia after administration of 5-fluorouracil due
      to a dihydropyrimidine dehydrogenase deficiency: high prevalence of the
      IVS14+1g>a mutation.
AB  - Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in
      the catabolism of 5-fluorouracil (5-FU), and it is suggested that patients with a
      partial deficiency of this enzyme are at risk of developing severe 5-FU
      associated toxicity. We evaluated the importance of DPD deficiency, gender and
      the presence of the IVS14+1G>A mutation in the etiology of 5-FU toxicity. In 61%
      of cases, decreased DPD activity could be detected in peripheral blood
      mononuclear cells. Furthermore, the number of females (65%) in the total group of
      patients appeared to be higher than the number of males (35%) (p = 0.03).
      Patients with partial DPD deficiency appeared to have a 3.4-fold higher risk of
      developing grade IV neutropenia than patients with normal DPD activity. Analysis
      of the DPYD gene of patients suffering from grade IV neutropenia for the presence
      of the IVS14+1G>A mutation showed that 50% of the patients investigated were
      heterozygous or homozygous for the IVS14+1G>A mutation. Adopting a threshold
      level for DPD activity of 70% of that observed in the normal population, 14% of
      the population is prone to the development of severe 5-FU-associated toxicity.
      Below this threshold level, 90% of individuals heterozygous for a mutation in the
      DPYD gene can be identified. Considering the common use of 5-FU in the treatment
      of cancer, the severe 5-FU-related toxicities in patients with low DPD activity
      and the apparently high prevalence of the IVS14+1G>A mutation, screening of
      patients at risk before administration of 5-FU is warranted.

PMID- 12209978
TI  - Intratumoral injection of dendritic cells after treatment of anticancer drugs
      induces tumor-specific antitumor effect in vivo.
AB  - We investigated the in vivo antitumor effects of intratumoral (i.t.)
      administration of dendritic cells (DC) after low-dose chemotherapy using
      cisplatin + 5-FU. Combination of i.t. injection of DC and systemic chemotherapy
      induced complete rejection of the treated tumor, MC38 murine adenocarcinoma.
      Furthermore, the antitumor effects were also observed on a distant tumor
      inoculated in the contralateral flank of the animal. When 10x the number of tumor
      cells were inoculated, the antitumor effect of the combination of DC after
      chemotherapy was also confirmed and in comparison to that of DC or chemotherapy
      alone, thereafter contributed to a greater prolongation of survival. To analyze
      the mechanisms of the systemic antitumor effect generated in this system, we
      assessed the cytolytic activity against inoculated tumors. The cytolytic activity
      of effector cells from treated animals was shown to be tumor-specific and was
      mainly CD8 and MHC Class-I (p < 0.01) restricted. CD4 and MHC Class-II treatment
      marginally inhibited the cytolytic activity but not significantly (p = 0.07, 0.08
      respectively). The cytolysis of effector cells was enhanced more significantly by
      the treatment of both DC and chemotherapy, than that of either DC or chemotherapy
      alone. Our study suggests that the strategy of i.t. injection of DC after low
      dose chemotherapy could be a powerful weapon to treat patients with cancer in the
      clinical settings.

PMID- 12209977
TI  - Viruses and Hodgkin disease: no evidence of novel herpesviruses in non-EBV
      associated lesions.
AB  - The Epstein-Barr virus (EBV) is associated with a proportion of cases of Hodgkin
      disease (HD) and this association is believed to be causal. Epidemiological
      studies suggest that an infectious agent is involved in the aetiology of young
      adult HD, however, cases in this age group are less likely to have EBV-associated
      disease than cases diagnosed in early childhood or older adult years. Molecular
      studies have failed to find a consistent association between HD and other
      candidate viruses, and the aetiology of non-EBV-associated cases remains obscure.
      We looked for evidence of herpesvirus infection in samples of non-EBV-associated
      HD using a highly sensitive, degenerate PCR assay. Despite exhaustive sequence
      analysis of PCR products, no novel herpesviruses were identified. These results
      suggest that it is extremely unlikely that a novel herpesvirus is involved in the
      pathogenesis of non-EBV-associated HD.

PMID- 12209979
TI  - BXD recombinant inbred mice represent a novel T cell-mediated immune response
      tumor model.
AB  - To develop a better animal model for studying the effects of the host environment
      in neoplasia, we injected various genetically well-characterized H-2(d) RI
      strains of BXD mice with syngeneic breast cancer cells (TS/A) and monitored the
      growth of tumors over time. There was a marked difference in the growth of the
      implanted breast cancer cells among the 14 BXD RI strains, with 4 patterns of
      tumor development being observed: in type I, the implanted tumor cells grew
      rapidly in the first 2 weeks, necrosis of the tumors was observed and metastases
      to the intestinal lymph nodes and pancreas was observed, causing death; in type
      II, the implanted tumor cells grew slowly and attained a size after day 50 that
      required killing the animal, with tumor necrosis being rare and metastases
      absent; in type III, the implanted tumor cells grew initially but underwent a
      slow decline after 4 weeks; and in type IV, the implanted tumor cells failed to
      develop. Apoptosis of the implanted tumor cells was responsible for the
      regression of tumor nodules. The T-cell immune response minimized tumor
      development in types III and IV since T-cell depletion of the BXD RI mice
      resulted in aggressively growing tumors in these strains.

PMID- 12209980
TI  - Apoptotic body-loaded dendritic cells efficiently cross-prime cytotoxic T
      lymphocytes specific for NA17-A antigen but not for Melan-A/MART-1 antigen.
AB  - DCs hold promise for cancer immunotherapy due to their functional ambivalence:
      iDCs internalize antigens, then mDCs trigger naive T-cell activation. However, no
      consensus has been reached concerning the optimal mode of antigen acquisition for
      efficient cross-priming of TAA-specific CTLs, and this remains a field of
      investigation. Here, we used highly purified apobodies derived from an HLA-A*0201
      negative melanoma line as a source of tumor antigens for HLA-A*0201 DCs. We
      compared in vitro mDCs loaded with apobodies to DCs loaded with antigenic
      peptides, NA17-A(1-9) and Melan-A/MART-1(26-35) A27L analogue, for their capacity
      to stimulate melanoma antigen-specific T cells from autologous PBLs. Apobody
      phagocytosis did not induce spontaneous DC maturation, but phagocytic DCs were
      still responsive to maturation signals, resulting in a functional ability to
      activate antigen-specific lymphocytes. NA17-A-specific T lymphocytes were
      activated by both types of stimulation, whereas only peptide-pulsed DCs
      stimulated the growth of Melan-A/MART-1-specific lymphocytes. We also observed a
      lack of staining of melanoma-derived apobodies with a Melan-A-specific MAb,
      suggesting protein alteration during apoptosis induction. After HLA-A*0201/NA17-A
      multimer sorting, antigen-specific lymphocytes induced by mature DCs loaded with
      either peptide or apobodies displayed similar functional capacity against peptide
      pulsed T2 cells and melanoma cells. Therefore, apobody-loaded DCs can achieve T
      cell priming similar to that induced by peptide-pulsed DCs, provided that the
      apoptotic process allows the preservation of antigen expression.

PMID- 12209981
TI  - Prognostic significance of cytokine modulation in non-small cell lung cancer.
AB  - Increased production of immunosuppressive interleukin-10 (IL-10) by non-small
      cell lung cancer (NSCLC) and increased serum IL-10 concentrations in NSCLC
      patients have recently been correlated to reduced survival. We earlier
      demonstrated suppression of IL-2 secretion in whole blood cell cultures of NSCLC
      patients. We now analyzed the influence of IL-2 secretion on survival in NSCLC
      patients and the influence of IL-10 on IL-2 secretion. The correlation of the IL
      2 producing ability of whole blood cells in response to PHA in 90 NSCLC-patients
      at the time of diagnosis to survival was calculated by Crit-level, the Kaplan
      Meier method and the log-rank test. With a cut-off value of IL-2 production of
      1,100 pg/ml by whole blood cells the difference in survival was significant with
      a p-value of 0.014. In the group with high and low IL-2, median survival was 14.1
      and 9.7 months, respectively. In the subgroup of 33 surgically-treated patients
      the difference in survival was significant with a p-value of 0.011. In 14
      patients with surgical resection of the tumor and high IL-2 at diagnosis and 19
      patients with surgical resection, but low IL-2 at diagnosis, median survival was
      86.2 and 11.3 months, respectively. Secretion of IL-2 in whole blood cell
      cultures from healthy individuals was inhibited in a dose-dependent manner upon
      addition of IL-10. Taken together, suppression of IL-2 secretion has prognostic
      significance for survival of NSCLC-patients and may be mediated by tumor-derived
      IL-10.

PMID- 12209982
TI  - Non-invasive molecular detection of bladder cancer recurrence.
AB  - Transitional cell carcinoma (TCC) is the most common bladder tumor and
      approximately 90% of bladder TCC are superficial at initial diagnosis. High
      recurrence rate and possible progression to muscle invasive disease that is
      eventually indicated for radical cystectomy are established features of these
      tumors. Therefore, reliable predictors of tumor recurrence are of critical
      importance for management of superficial bladder TCC. Successful molecular
      diagnosis of bladder cancer by detecting genetic lesions: loss of heterozygosity
      (LOH) or microsatellite instability (MSI) in cells exfoliated in urine has been
      reported by several groups including ours. The aim of our study was to evaluate
      the predictive potential of microsatellite analysis of cells exfoliated in urine
      in the detection of superficial bladder TCC recurrence. We studied 47 Caucasian
      patients with confirmed superficial bladder TCC (37 pTa, 10 pT1) at initial
      diagnosis. Blood samples were obtained once from every patient whereas urine
      samples were collected before each cystoscopy (initial and follow-up). Matched
      DNAs from blood and urine were subjected to microsatellite analysis in a blinded
      fashion. The follow-up period ranged 12-48 months after tumor resection.
      Microsatellite analysis correctly identified 94% (44/47) of primary tumors and
      92% (12/13) of tumor recurrences. Interestingly enough, 75% (9/12) of tumor
      recurrences were molecularly detected 1-9 months before cystoscopic evidence of
      recurrent disease. This study demonstrated clearly that not only urine
      microsatellite analysis reliably detected superficial bladder tumors, but also
      was a reliable test for detecting and predicting tumor recurrence in Caucasian
      patients. These results warrant multicenter randomized trials.

PMID- 12209983
TI  - On cancer risks in second-generation immigrants to Sweden.

PMID- 12209986
TI  - Proneural and proneuroendocrine transcription factor expression in cutaneous
      mechanoreceptor (Merkel) cells and Merkel cell carcinoma.
AB  - Merkel cells form part of the peripheral neuroendocrine system of the skin and
      act as mechanoreceptors in touch response. Merkel cell carcinoma (MCC) is a rare,
      aggressive disease with similarities to small cell lung cancer (SCLC), which is
      also of neuroendocrine origin. We previously identified a novel DNA binding
      protein complex specific for MCC suspension cell lines, termed Merkel nuclear
      factor (MNF) by its binding to the POU-IV family DNA binding consensus sequence.
      Here we report that MNF contains the POU-IV family member Brn-3c and that Brn-3c
      is expressed in normal Merkel cells. Additionally, Brn-3c protein reactivity is
      restricted to a subset of MCC biopsies and is not seen in biopsies revealing
      adherent, variant cell lines lacking neuroendocrine markers. Recently, proper
      development of murine Merkel cells was shown to require the proneural basic helix
      loop-helix transcription factor, atonal family member, MATH1. We demonstrate a
      correlation between Brn-3c and HATH1 reactivity in MCC biopsies and cell lines
      with retention of neuroendocrine phenotype. In SCLC, the related basic helix-loop
      helix transcription factor HASH1 is responsible for neuroendocrine phenotype, but
      HASH1 transcripts were not detected in MCC cell lines. We propose that HATH1 and
      Brn-3c may form a transcriptional hierarchy responsible for determining
      neuroendocrine phenotype in Merkel cells and that lack of Brn-3c and/or HATH1 in
      MCC may indicate a more aggressive disease requiring closer patient follow-up.

PMID- 12209987
TI  - Antagonistic and agonistic effects of quinazoline tyrosine kinase inhibitors on
      mutant EGF receptor function.
AB  - A mutated form of the EGF receptor (EGFRvIII), resulting from deletion of exons 2
      7, is an oncogenic protein that is expressed in multiple human tumors. This
      mutation induces ligand-independent activation of the EGFR tyrosine kinase and
      thereby can initiate unregulated cell growth and tumorigenesis. Thus, inhibition
      of the kinase activity of EGFRvIII is a potential means of suppressing its
      oncogenic properties. Certain tyrosine kinase inhibitors (tyrphostins)
      specifically inhibit the wild-type EGFR and thereby inhibit tumor growth both in
      vitro and in vivo. We demonstrate that the quinazoline tyrphostins AG 1478 and AG
      1517 can suppress morphologic transformation of cell lines by EGFRvIII.
      Quinazolines were found to inhibit receptor autophosphorylation and signaling
      through MAP kinase, but had minimal effects on association of EGFRvIII with
      Grb2/SOS. Low concentrations of quinazoline also increased receptor dimerization
      and phosphotyrosine content. This was associated with increases in colony
      formation in soft agar and increased invasion through matrigel for AG 1478. Thus,
      both AG 1478 and AG 1517 can inhibit multiple EGFRvIII signaling pathways, but at
      low concentrations AG 1478 can enhance colony formation, presumably related to
      augmented homodimerization of the receptor and activation of downstream
      signaling.

PMID- 12209988
TI  - Target validation for genomics using peptide-specific phage antibodies: a study
      of five gene products overexpressed in colorectal cancer.
AB  - Genomic approaches are providing a wealth of information on differential gene
      expression in cancer. To identify the most interesting genes amongst the many
      identified, high-throughput methods for analysis of genes at the translational
      level are required. We have used a rapid method for the in vitro selection of
      antibodies to peptide antigens for the generation of probes to 5 gene products
      that we have found to be overexpressed in colorectal cancer. The rationale of our
      study was to select a non-immune phage displayed human antibody library on
      peptides designed from the coding regions of the gene sequences and to verify
      whether such antibodies would be suitable probes for the parental protein in
      immunohistochemical and Western blot analysis. After the generation of a profile
      of genes overexpressed in primary colorectal cancer (CRC) we selected 5 genes,
      Ese-3b, Fls353, PBEF, SPARC and Smad5 for a more detailed analysis using phage
      display-derived antibodies. For these 5 antigens we designed 14-20 amino acid
      peptides predicted to be exposed on the surface of the parental protein.
      Selection of a large phage displayed antibody library resulted in specific
      antibodies for 6 of 8 different peptides with between 2 and 15 different
      antibodies isolated per peptide. Of 20 antibodies tested, 2 antibodies recognized
      the putative parental protein from primary CRC tissue. An antibody specific for a
      PBEF-derived peptide (Fab/PBEF-D4) was shown to recognize a protein product of
      the expected molecular weight in Western blotting and showed overexpression in n
      = 6/8 matched tumor/normal protein lysates. Furthermore, in immunohistochemistry
      this antibody showed restricted staining of the tumor stromal compartment with no
      detectable staining of epithelial cells. The discovery that PBEF is overexpressed
      in cancer is unexpected given that the normal function of PBEF is as a cytokine
      required for the maturation of B cell precursors. We also report on the isolation
      of an antibody (Fab/SMAD-50) specific for a Smad5-derived peptide that showed
      cytoplasmic staining of epithelial cells in both CRC tumor and matched normal
      mucosa. Fab/SMAD-50 also bound to a group of proteins in Western blotting with
      molecular weights consistent with belonging to the Smad family. These antibodies
      may be suitable probes for further investigation of the roles of PBEF and Smad5
      in cancer. The amenability of phage display to automation suggests that this
      approach may be developed for implementation on a genomics scale. Indeed, the
      large-scale generation of antibody probes that can be used to study protein
      expression in situ would be of great value in target validation for functional
      genomics.

PMID- 12209990
TI  - Combined karyotyping, CGH and M-FISH analysis allows detailed characterization of
      unidentified chromosomal rearrangements in Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine tumor of the
      skin. Cytogenetic studies have indicated that deletions and unbalanced
      translocations involving chromosome 1 short arm material occur in 40% of the
      investigated cases. Recurrent chromosomal imbalances detected by comparative
      genomic hybridization (CGH) analysis were loss of 3p, 10q, 13q and 17p and gains
      of 1q, 3q, 5p and 8q. In order to study genomic aberrations occurring in MCC in
      further detail, we combined karyotyping, CGH and multiplex-fluorescence in situ
      hybridization (M-FISH), a strategy that proved to be successful in the analysis
      of other malignancies. Analysis of 6 MCC cell lines and 1 MCC tumor revealed
      mostly near-diploid karyotypes with an average of 5 chromosomal rearrangements.
      The observed karyotypic changes were heterogeneous, with 3-27 breakpoints per
      case, leading to imbalance of the involved chromosomal regions that was confirmed
      by CGH. Chromosomal rearrangements involving the short arm of chromosome 1, the
      long arm of chromosome 3 and gain of 5p material were the most frequently
      observed abnormalities in our study. In keeping with previous observations, this
      series of MCCs showed no evidence for high-level amplification. We provid a
      detailed description of chromosomal translocations occurring in MCC that could be
      useful to direct future intensive investigation of these chromosomal regions.

PMID- 12209989
TI  - Escape of p53 protein from E6-mediated degradation in HeLa cells after cisplatin
      therapy.
AB  - We previously reported that therapy of human cervical carcinoma HeLa cells with
      CP induced segregation of nucleoli and changes of nuclei characteristic of
      apoptosis. We raised the question of whether p53 can be reactivated by
      chemotherapy in HeLa cells despite the presence of HPV-encoded E6 activity.
      Cellular levels of p53 protein increased after CP treatment, reaching a maximum
      after 6 hr. p53 protein accumulated preferentially in the nucleoli, with a peak
      after 15 hr. CP-induced nucleolar targeting of p53 appears to be selective
      because p73, another member of the p53 gene family, accumulated primarily in
      nuclei in response to CP. Monitoring of the intranuclear distribution of Hdm-2, a
      negative regulator of p53, revealed this protein in the nucleoli of untreated
      controls translocated into chromatin during CP therapy. Interestingly, p14(ARF)
      showed an inverse intranuclear redistribution. Proteasome inhibitors were not
      able to mimic the effect of CP on p53 levels. Since the reduced stability of wild
      type p53 protein in HeLa cells is a consequence of its enhanced ubiquitination by
      virally encoded E6 protein, resulting in its accelerated degradation, we checked
      the cellular level of E6 during CP therapy. Six hours after application of CP, E6
      protein expression was markedly reduced. This coincided with the increase of
      cellular p53 and preceded the nucleolar accumulation of p53 protein, indicating
      that repression of virally coded E6 protein by CP contributes to the restoration
      of p53 expression.

PMID- 12209991
TI  - Autoantibodies to tubulin are specifically associated with the young age onset of
      the nasopharyngeal carcinoma.
AB  - By far the highest incidence of the Epstein-Barr virus (EBV)-associated
      nasopharyngeal carcinomas in young subjects was found in North Africa, a region
      of intermediate risk for adults. We used the immunofluorescence analysis and
      ELISA to characterize the presence of IgG autoantibodies to the cytoskeleton and
      nuclear proteins in sera of 82 Tunisian patients with primary nasopharyngeal
      carcinoma and those of 82 healthy subjects. To assess the specificity of the sera
      autoreactivity, inhibition tests were carried out using free autoantigens.
      Analysis of sera autoreactivity in patients with nasopharyngeal carcinoma and in
      control subjects showed that 23% of the patients had serum reactivity against
      more than 1 autoantigen tested compared to 1.2% in the control group (p = 10(
      4)). The most frequent auto reactivity in patient's sera was found with tubulin
      and nuclear proteins (19.5% and 22% respectively vs. 6.1% and 1.2% in controls).
      The IgG auto reactivity inhibition studies indicate that all autoantigens, except
      native DNA, showed low values of IC(50) (concentration of antigen causing 50%
      inhibition of the antibody binding) reflecting the high affinity of these IgG
      autoantibodies. When patients and controls were stratified according to their
      age, IgG autoantibodies to tubulin were found specifically associated with the
      young age onset of the nasopharyngeal carcinoma (age under 25 years). IgG auto
      reactivity comparison before and after cancer therapy showed that only anti
      tubulin reactivity was significantly affected by treatment. Our results
      demonstrate that the autoantibodies to the cytoskeleton and nuclear proteins are
      associated with the nasopharyngeal carcinoma in Tunisians. The anti-tubulin IgG
      autoantibodies may represent a serologic marker for the nasopharyngeal carcinoma
      in children and adolescents Tunisians.

PMID- 12209992
TI  - Indoleamine 2,3-dioxygenase contributes to tumor cell evasion of T cell-mediated
      rejection.
AB  - The priming of an appropriate anti-tumor T cell response rarely results in the
      rejection of established tumors. The characteristics of tumors that allow them to
      evade a T cell-mediated rejection are unknown for many tumors. We report on
      evidence that the expression of the immunosuppressive enzyme, indoleamine 2,3
      dioxygenase (IDO) by mononuclear cells that invade tumors and tumor-draining
      lymph nodes, is 1 mechanism that may account for this observation. Lewis lung
      carcinoma (LLC) cells stimulated a more robust allogeneic T cell response in
      vitro in the presence of a competitive inhibitor of IDO, 1-methyl tryptophan.
      When administered in vivo this inhibitor also resulted in delayed LLC tumor
      growth in syngeneic mice. Our study provides evidence for a novel mechanism
      whereby tumors evade rejection by the immune system, and suggests the possibility
      that inhibiting IDO may be developed as an anti-cancer immunotherapeutic
      strategy.

PMID- 12209993
TI  - Role for beta3 integrins in human melanoma growth and survival.
AB  - The role of alphaIIbbeta3 integrin in regulating platelet function is well
      appreciated, whereas its role in tumor progression and metastasis is not. The
      purpose of our study was to determine a functional relevance to expression of
      alphaIIbbeta3 integrin in cells derived from human solid tumors. A study of human
      melanoma biopsies (n = 24) showed that alphaIIbbeta3 expression increased with
      tumor thickness, which is indicative of metastatic propensity. Expression of
      alphaIIbbeta3 was 8% (+/-1.8), 33% (+/-10.4) and 62% (+/-5) in melanomas ranging
      in thickness from 0-1.5 mm, 1.5-4.0 mm and >4 mm, respectively; alphavbeta3 was
      equally high all categories. To determine biological function, we stably
      transfected alphaIIbbeta3 into human melanoma cells that express alphavbeta3, but
      not alphaIIbbeta3. Surface expression of alphavbeta3 remained unaltered between
      alphaIIbbeta3 (+) and mock transfected counterparts. The alphaIIbbeta3 (+) cells
      possessed increased ability to adhere, spread and migrate on fibrinogen. They had
      decreased ability to attach, spread and migrate on vitronectin.
      Immunocytochemistry showed that expression of alphaIIbbeta3 displaced alphavbeta3
      from focal contact points. When implanted subcutaneously into SCID mice, the
      alphaIIbbeta3 (+) cells developed approximately 4-fold larger tumors when
      compared to their mock counterparts and the level of apoptosis was reduced within
      the tumors. Results suggest that co-expression of the 2 beta3 integrins,
      alphavbeta3 and alphaIIbbeta3, in human melanoma cells enhanced cell survival and
      promoted growth in vivo.

PMID- 12209994
TI  - A geographic analysis of prostate cancer mortality in the United States, 1970-89.
AB  - The recently published atlas of cancer mortality in the United States revealed
      that prostate cancer mortality rates were elevated among white men in the
      Northwest, the Rocky Mountain states, the north-central area, New England and the
      South Atlantic area, and among black men in the South Atlantic area. Here we
      determine whether the elevated regional rates were statistically different from
      rates in the rest of the country and whether the pattern can be explained by
      selected regional characteristics. A spatial scan statistic was applied to county
      based mortality data from 1970 through 1989 to identify geographic clusters of
      the elevated rates for prostate cancer. Five clusters of elevated mortality were
      detected in white men (p < 0.005) and 3 in black men (p = 0.0001-0.056). For
      white men, the primary cluster was in the northwestern quadrant, followed by
      clusters in New England, the eastern part of the north-central area, the mid
      Atlantic states and the South Atlantic area, whereas for black men the primary
      cluster was in the South Atlantic area, followed by clusters in Alabama and the
      eastern part of the north-central area. Further analyses of these clusters
      revealed several significant subclusters (p < 0.05). None of the selected
      demographic and socioeconomic factors, separately or collectively, accounted for
      the primary clusters in the U.S. white and black populations. The patterns
      observed could not be attributed to selected demographic or socioeconomic
      characteristics but should provide leads for further study into the risk factors
      and the medical or reporting practices that may contribute to geographic
      variation in mortality from prostate cancer.

PMID- 12209995
TI  - Sun exposure predicts risk of ocular melanoma in Australia.
AB  - Previous studies examining sun exposure and ocular melanoma have produced
      inconsistent results. We investigated this association in a population-based case
      control study in Australia. Cases (n = 290) aged 18-79 years were diagnosed
      between January 1996 and July 1998. Controls (n = 893) were randomly selected
      from the electoral rolls and frequency-matched to cases by age, sex and state. A
      self-administered questionnaire and a telephone interview measured sun exposure
      on weekdays and weekends at 10, 20, 30 and 40 years of age and over the whole of
      life for specific jobs and recreations. Multivariate logistic regression models
      of ocular melanoma and sun exposure contained age, sex, region of birth, eye
      color and measures of ocular and cutaneous sun sensitivity as covariates. Choroid
      and ciliary body melanoma (n = 246) was positively associated with time outdoors
      on weekdays and, less persuasively, total time outdoors but not ambient solar
      irradiance. Odds ratios increased with increasing exposure to OR 1.8 (95%
      confidence interval 1.1-2.8) for the highest quarter of sun exposure on weekdays
      up to 40 years of age for men and women together. The strongest positive
      associations were for total exposure up to 40 years of age, lifetime occupational
      exposure and total exposure at about 20 years of age in men; all had odds ratios
      between 2 and 3 in the highest exposure categories. There was inconclusive
      evidence for an association between sun exposure and iris (n = 25) or
      conjunctival (n = 19) melanomas. Sun exposure is an independent risk factor for
      choroidal and ciliary body melanoma in Australia.

PMID- 12209996
TI  - Intraperitoneal bispecific antibody (HEA125xOKT3) therapy inhibits malignant
      ascites production in advanced ovarian carcinoma.
AB  - Bispecific antibody HEA125 x OKT3 was shown to redirect T lymphocytes toward
      carcinoma cells and to induce tumor cell lysis in vitro. Preclinical studies have
      demonstrated that tumor-associated lymphocytes (TAL) derived from malignant
      ascites can be used as effector cells with a high efficacy and without prior
      stimulation. These data provided the rationale for a clinical trial to
      investigate whether bsAb HEA125 x OKT3 is also able to induce tumor cell lysis in
      vivo and can be used for local treatment of malignant ascites arising from
      ovarian carcinoma. Ten ovarian carcinoma patients presenting with malignant
      ascites resistant to chemotherapy were enrolled in the study. They received
      weekly intraperitoneal injections of 1 mg bsAb diluted in 500 ml NaCl solution to
      allow homogeneous antibody distribution within the peritoneal cavity. All
      patients responded clinically well to the therapy. Eight patients experienced a
      complete and 2 patients a partial reduction of ascites production. A decrease or
      stabilization of tumor marker CA125 was detected in the sera of 8 patients. Only
      WHO Grade I and II toxicity was observed including mild fever, chills and
      allergic eczema. Thus, intraperitoneal application of bsAb HEA125 x OKT3 appears
      to be an easy and cost effective palliative treatment for ovarian carcinoma with
      recurrent ascites that leads to a substantially increased quality of life for the
      patients. During therapy TNF-alpha concentrations raised markedly in the ascites
      fluid whereas VEGF and sFLT-1 ascites levels declined. This indicates that not
      only T cell-mediated tumor cell lysis but also changes in vascular permeability
      due to downregulation of VEGF and its receptors might be responsible for the
      beneficial therapeutic effect.

PMID- 12209997
TI  - Cancer-testis antigen expression in uterine malignancies with an emphasis on
      carcinosarcomas and papillary serous carcinomas.
AB  - The cancer testis (CT) family of antigens are expressed in certain malignant
      neoplasms and are silent in normal adult tissues, except for the testis.
      Expression of 2 members of this family, MAGE-A4 and NY-ESO-1, has been described
      recently in germ cell tumors, malignant melanomas, certain carcinomas and
      sarcomas. Our study is the first to describe the expression pattern of CT
      antigens in uterine neoplasms. Ninety-eight cases of uterine neoplasms, including
      41 endometrioid, 19 papillary serous and 7 clear cell carcinomas, 22
      carcinosarcomas and 9 endometrial stromal sarcomas were studied.
      Immunohistochemistry was carried out with the 57B monoclonal antibody that
      recognizes predominantly the MAGE-A4 antigen in paraffinized tissues and the
      D8.38 antibody that recognizes NY-ESO-1. MAGE-A4 expression was found to be
      present in 12% of the endometrioid adenocarcinomas, 63% of the papillary serous
      carcinomas and 91% of the carcinosarcomas. Within the tumor population the extent
      of MAGE-A4 expression was highest in the carcinosarcomas. In 12 of 22 positively
      staining carcinosarcomas more than 50% of the tumor cells expressed MAGE-A4. NY
      ESO-1 expression was seen in 19% of the endometrioid adenocarcinomas, 32% of the
      papillary serous carcinomas and in 45% of the carcinosarcomas. CT antigen
      immunoreactivity was observed in both the carcinomatous and sarcomatous
      components of the carcinosarcomas and strong correlation between MAGE-A4 and NY
      ESO-1 expression was present in individual cases. In summary, strong MAGE-A4
      expression and to a lesser degree NY-ESO-1 expression is characteristic of the
      vast majority of uterine carcinosarcomas and a major subset of papillary serous
      carcinomas. These results suggest that CT antigen expression by these tumors may
      represent a novel target for immunotherapy.

PMID- 12209998
TI  - CDH1 c-160a promotor polymorphism is not associated with risk of stomach cancer.
AB  - We have combined data from case control studies designed to test the hypothesis
      that the c-160a promotor polymorphism in the gene coding for the cell adhesion
      molecule E-cadherin (CDH1) is associated with stomach cancer. A total of 899
      individuals (433 patients and 466 controls) were analyzed. The genotype
      frequencies did not differ significantly between cases and controls, and the
      genotype-specific risks were not significantly different from unity, with an odds
      ratio for heterozygotes compared with the common homozygote of 1.3 (95% CI 0.98
      1.8) and 1.2 (0.68-2.0) for rare homozygotes compared with common homozygotes. We
      found no evidence for differences in risk for the intestinal- and diffuse-type
      histopathologic subgroups.

PMID- 12209999
TI  - Role of Wnt pathway in medulloblastoma oncogenesis.
AB  - To clarify the roles of Wnt pathway in medulloblastoma oncogenesis,
      immunohistochemical staining of beta-catenin and Wnt-1 and genomic analyses of
      CTNNB1 (beta-catenin) and AXIN1 (axin 1) were examined in 23 sporadic cases.
      Accumulation of beta-catenin in tumor cells was immunohistochemically proven in 5
      cases; 2 cases showed positive immunoreactivity for Wnt-1 and another 2 showed
      mutation of either CTNNB1 or AXIN1. AXIN1 mutation was in exon 3, corresponding
      to GSK-3beta binding site and CTNNB1 mutation was in exon 3, corresponding to its
      phosphorylation site. Disruption of these proteins could result in upregulation
      of the Wnt signaling and accumulation of beta-catenin, followed by cell
      proliferation and medulloblastoma oncogenesis.

PMID- 12210000
TI  - Analysis of the human progesterone receptor gene polymorphism PROGINS in Austrian
      ovarian cancer patients.

PMID- 12210003
TI  - Folic acid and NTD--continued: genetic variants.

PMID- 12210004
TI  - Coarctation of the aorta in two siblings from a triplet, diabetic, in vitro
      fertilization pregnancy.

PMID- 12210005
TI  - Is omphalocele a consequence of high maternal estrogen levels?

PMID- 12210007
TI  - Classification of drugs for teratogenic risk: an anachronistic way of counseling.

PMID- 12210008
TI  - The heart of Turner syndrome: small matters.

PMID- 12210009
TI  - Turner syndrome morphology and morphometrics: Cardiac hypoplasia as a cause of
      midgestation death.
AB  - BACKGROUND: A female fetus with massive truncal-limb hydrops and large,
      loculated, nuchal hygromas in midgestation is highly likely to have Turner
      syndrome. This phenotype is recognized to be usually lethal, with only more
      mildly affected fetuses surviving to term birth. METHODS: The morphology and
      morphometrics of 117 midgestation fetuses with phenotypic Turner syndrome were
      analyzed. RESULTS: More than 90% of fetuses with phenotypic Turner syndrome were
      found to have heart weights below the 2.5 centile, as well as lung hypoplasia and
      restricted limb growth for brain weight standards, although brain weight was only
      mildly reduced for gestational age. In contrast, subnormal heart weight was much
      less common among fetuses with other etiologies of hydrops, hygromas, or pleural
      effusions. CONCLUSIONS: We hypothesize that myocardial hypoplasia is a primary
      defect in Turner syndrome, and it leads to or is a major contributor to the
      phenotypic features that end in midgestational death.

PMID- 12210010
TI  - Fetal methotrexate and misoprostol exposure: the past revisited.
AB  - BACKGROUND: Fetal aminopterin/methotrexate syndrome was described nearly 50 years
      ago when these agents were first used as abortifacients. Physicians essentially
      stopped using these agents when the associated anomalies were recognized. Over
      the last several years the use of methotrexate with or without misoprostol for
      management of ectopic pregnancy and medical terminations of pregnancy has
      increased. METHODS: A 23-year-old female sought a termination at eight weeks
      gestation. She was given methotrexate followed by misoprostol. RESULTS: The
      medical termination was unsuccessful. The patient elected to continue the
      pregnancy secondary to financial considerations. She presented at 39 weeks
      without intervening prenatal care. She was diagnosed with severe preeclampsia. At
      delivery the infant was hypotonic and growth restricted with multiple anomalies.
      CONCLUSIONS: Physicians are increasingly using methotrexate with or without
      misoprostol for treatment of ectopic pregnancies and medical terminations.
      Clinicians need to be aware of the characteristic teratologic effects of these
      two agents.

PMID- 12210011
TI  - Frozen-sectioning yields similar results as traditional methods for fetal
      cephalic examination in the rat.
AB  - BACKGROUND: An integral component of developmental toxicity studies is the
      evaluation of fetal anatomy, which consists of external, visceral, and skeletal
      examinations. The visceral examination includes an assessment of the fetal head
      which, in the rat, is typically completed after chemical fixation. Because
      chemical fixation requires approximately 7 days, a comprehensive visceral
      examination, including the head, of the fetal rodent cannot be completed at the
      time of cesarean section. An alternative method to chemical fixation was desired,
      whereby one could complete an overall visceral examination at the time of
      cesarean section. In addition, the method would also have to present fetal
      cranial structures in a manner consistent with that derived after chemical
      fixation. METHODS: Pregnant Sprague-Dawley rats were administered either 6
      aminonicotinamide (6AN), 6 or 12 mg/kg on gestation day 13, or all-trans retinoic
      acid (RA) 5 or 25 mg/kg on gestation days 9 and 10, untreated dams served as a
      control group. On gestation day 20, fetuses were sacrificed and removed via
      cesarean section and one-half of the fetuses from each litter were placed in
      Bouin's solution (chemical fixation) and the remaining fetuses maintained under
      refrigeration until just before frozen tissue preparation (freeze fixation).
      Sectioning of the fetal head was similarly conducted after either chemical or
      frozen-fixation. Fetal cranial findings observed after chemical fixation were
      compared to those observed after frozen-fixation in the untreated control and 6AN
      and RA-treated groups. RESULTS: The incidence and severity of the cranial
      findings, including effects on the eye, brain, and palate, were similarly
      observed, regardless of fixation method. CONCLUSIONS: A frozen sectioning method
      for evaluation of the fetal head, yielding results comparable to those derived
      after chemical fixation, is described. This procedure provides a viable
      alternative to chemical fixation, and allows the teratologist to complete a
      comprehensive fetal visceral examination at the time of cesarean section.

PMID- 12210012
TI  - Aryl hydrocarbon receptor nuclear translocator 2 (ARNT2): structure, gene
      mapping, polymorphisms, and candidate evaluation for human orofacial clefts.
AB  - BACKGROUND: Nonsyndromic orofacial clefts have an estimated incidence of 1/1000
      live births. Population genetic and embryologic studies suggest that cleft palate
      only (CPO) may be a distinct clinical entity from cleft lip with or without cleft
      palate (CL/P). Both CPO and CL/P are thought to be multifactorial in etiology,
      with evidence indicating that genetic, environmental, and developmental
      determinants may all play a role. The ARNT2 gene localizes to a conserved linkage
      group on mouse chromosome 7 that is syntenic with human chromosome 15q23-25. This
      chromosomal region was previously identified as a teratogen-induced clefting
      susceptibility locus in a genome-wide scan of AXB and BXA recombinant inbred
      mice. Arnt2 is expressed in the first branchial arch in mice. The teratogen
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) acts through the aryl hydrocarbon
      receptor (Ahr) pathway to produce dose-dependent CPO and thymic wasting in mice
      exposed in utero. Arnt2 and Ahr proteins dimerize in vitro. TCDD exposure is also
      associated with orofacial clefting in children of parents involved in
      agricultural work. METHODS: To determine whether ARNT2 influences human
      craniofacial development, we identified the human ARNT2 gene and conducted
      genomic structural analysis. Mutational screening was performed in infants with
      nonsyndromic CPO or CL/P who were identified by the Iowa Birth Defects Registry.
      RESULTS: A common amino acid polymorphism was detected but, no obvious disease
      causing mutations were detected by SSCP analysis. The microsatellite marker,
      GATA89D04 (D15S823) was identified within intron 11 of the human ARNT2 gene, and
      linkage disequilibrium of nonsyndromic CPO and CL/P parent-infant trios was
      conducted. CONCLUSIONS: No association was demonstrated with CPO (n = 45) and
      CL/P (n = 37). Teratology 66:85-90, 2002.

PMID- 12210013
TI  - Talipes equinovarus and maternal smoking: a population-based case-control study
      in Washington state.
AB  - BACKGROUND: Talipes equinovarus (TEV), also called congenital idiopathic
      clubfoot, true clubfoot and common clubfoot, is one of the most common major
      birth defects. Its correction is often difficult and expensive. Its etiology is
      poorly understood and few analytic epidemiological studies have been devoted to
      exploring specific risk factors for TEV. METHODS: Our population-based study
      consists of 239 documented cases of idiopathic TEV obtained from hospital and
      outpatient sources and 365 controls identified via random digit dialing from five
      Western Washington counties. Structured maternal interviews were conducted by
      trained interviewers and multiple logistic regression used to evaluate
      associations between maternal smoking and birth of a child with TEV. RESULTS: Our
      study shows strong associations between maternal smoking and idiopathic TEV. Case
      mothers were more likely to have smoked during pregnancy (OR = 2.2; 95% CI = 1.5,
      3.3). Increased TEV risk was seen with increased smoking and estimates ranged
      from 1.5 for the lightest smokers to 3.9 for the heaviest smokers. Gender
      specific differences in risk were also noted with risk estimates of 1.8 (95% CI =
      1.2, 3.0) for boys whose mothers smoked during pregnancy and 2.8 (95% CI = 1.4,
      5.4) for girls. Trends for increased risk with higher numbers of cigarettes were
      noted for both genders. For isolated TEV, the overall odds ratio (OR) for smoking
      was 2.4 (95% CI = 1.6, 3.6) with a range from 1.4-4.6. No confounders were noted.
      CONCLUSIONS: As postulated, maternal smoking during pregnancy appears to increase
      the risk of having a child with idiopathic clubfoot and the number of cigarettes
      smoked influence that risk. Further delineation of dose-response is warranted as
      are continued efforts to decrease maternal smoking during pregnancy.

PMID- 12210017
TI  - The Commission on Cancer of the American College of Surgeons: restructuring to
      meet the demand for quality cancer care and cancer data.

PMID- 12210018
TI  - Is abdominoperineal resection a good option for stage IV adenocarcinoma of the
      distal rectum?
AB  - BACKGROUND AND OBJECTIVES: The management of the primary lesion in patients with
      stage IV adenocarcinoma of the distal rectum is controversial. An
      abdominoperineal resection (APR) may be a good option. METHODS: A retrospective
      analysis of the medical records of 21 patients with stage IV distal rectal
      adenocarcinoma treated with an APR between January 1991 to December 2000 was
      performed. RESULTS: All patients had an Eastern Cooperative Oncology Group (ECOG)
      performance status of 1 and normal preoperative alkaline phosphatase and total
      bilirubin levels. Twelve patients (92%) with liver metastases had less than 25%
      of total liver volume involvement. Twenty patients (95%) had complete resolution
      of their symptoms related to the primary rectal cancer. The median follow-up was
      19 months (range 3-92 months), with a median survival of 21.6 months and a 2-year
      overall survival of 34%. CONCLUSIONS: Patients with stage IV distal rectal
      adenocarcinoma who have a good performance status, normal preoperative liver
      function tests, and minimal metastatic disease to the liver can be offered
      resective surgery.

PMID- 12210019
TI  - Biliary carcinoembryonic antigen in the diagnosis of occult hepatic metastases
      from colorectal cancer.
AB  - BACKGROUND AND OBJECTIVES: Twenty five percent of patients who undergo radical
      surgical treatment for colorectal cancer have occult hepatic metastases that
      become evident during the follow-up period. We evaluated whether biliary
      carcinoembryonic antigen (CEA) measurements could be used in these patients to
      diagnose occult hepatic metastases. METHODS: Three groups of patients were
      enrolled in the study. The first group consisted of patients treated for
      lithiasis of the common bile duct, the second group was affected by colorectal
      cancer and evident hepatic metastases, and the third group of patients underwent
      radical surgical treatment for colorectal cancer but had no evident hepatic
      metastases. RESULTS: In the first study group, mean biliary CEA level was 0.52
      ng/mL (normal value: 0-5 ng/mL) (diagnostic accuracy: 100%), 83.3 ng/mL in the
      second group (diagnostic accuracy: 91%) and 3.9 ng/mL in the third group. We
      registered only one false-positive result in the third group, whereas biliary CEA
      level was above normal values in the three patients in whom hepatic metastases
      developed (diagnostic accuracy: 89.5%). CONCLUSIONS: This study suggests that
      biliary CEA determination could represent an important method to select patients
      affected by occult hepatic metastases for inclusion in appropriate treatment
      protocols.

PMID- 12210020
TI  - Are the axillary lymph nodes treated by standard tangent breast fields?
AB  - BACKGROUND AND OBJECTIVES: With the increasing use of sentinel lymph node biopsy,
      a growing proportion of women with early-stage invasive breast cancer are
      undergoing breast conserving surgery without a formal axillary lymph node
      dissection. A frequent question raised is whether the level I-II axillary lymph
      nodes are treated with standard breast tangent fields. In an attempt to answer
      this question, surgical clips placed at the time of the level I-II axillary lymph
      node dissection were used as a surrogate for the location of the nodes and the
      simulator films for tangent fields of 45 patients were analyzed. METHODS: Study
      criteria were as follows: five or more clips placed in the axilla, and all clips
      and the humeral head visualized on the medial tangent film. Clips were scored as
      "in" or "out" of the tangent field, as defined by the delineator wires. All
      technical parameters were analyzed to determine whether any reproducible
      techniques would consistently include all of the clips and, hypothetically, the
      axillary nodes at levels I and II. RESULTS: All clips were included in the medial
      tangent breast radiation field in only 38% (17 of 45) of cases. CONCLUSIONS: The
      standard, two-field tangent breast fields do not reliably encompass the all level
      I-II axillary lymph nodes as defined by this study, but some of the nodes were
      treated in all 45 cases.

PMID- 12210022
TI  - Rationale and definition of the lateral extension of the inguinal lymphadenectomy
      for vulvar cancer derived from an embryological and anatomical study.
AB  - BACKGROUND AND OBJECTIVES: The objective of the present study was to define the
      location of the most lateral superficial inguinal node lying along the inguinal
      ligament, through an embryological and anatomotopographical study, in order to
      rationalize the lateral extension of the groin lymphadenectomy in vulvar cancer.
      METHODS: Sections of the upper portion of the femoral triangle belonging to three
      human fetuses, whose crown-rump (CR) length ranged from 70 to 310 mm,
      corresponding to a developmental age of 11 and 35 weeks, were studied. In
      addition, for an objective topographical evaluation of the disposition of the
      superficial inguinal lymph nodes, adult cadavers photographs of dissected
      Scarpa's triangle, reported in anatomical atlases, were analyzed. RESULTS: Both
      the embryological investigation and the anatomotopographical evaluation on
      cadavers photographs demonstrate that the most lateral superficial inguinal lymph
      node does not rise above the medial margin of the sartorius muscle, nor far
      lateral to the point where the superficial circumflex iliac vessels cross the
      inguinal ligament. CONCLUSIONS: On the basis of the present study, the authors
      believe that the superficial circumflex iliac vessels could represent the lateral
      surgical landmark, easily detectable, at which the inguinal lymphadenectomy
      should cease. Therefore, there is no need to extend the lateral excision to the
      anterior superior iliac spine. Finally, leaving the fatty tissue laterally to
      these vessels, some lymphatic channels could be preserved, decreasing the
      incidence and the entity of wound seroma and lymphedema.

PMID- 12210023
TI  - Biologic and imaging diagnosis of lymph node metastasis in esophageal carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Few reports have described the combined use of
      biologic and imaging techniques in the diagnosis of lymph node metastasis. We
      prospectively evaluated lymph node metastasis diagnosed by biologic and imaging
      means in patients with esophageal carcinoma. METHODS: Preoperative ultrasound and
      endoscopic ultrasound (EUS) examination were performed in 80 patients. Biopsy
      specimens were immunohistochemically examined using cyclin D1 (CD1) and
      desmoglein 1 (DG1) antibodies, and tumors were classified into three grades.
      RESULTS: The sensitivity, specificity, and accuracy values of ultrasound
      examination were 88.2, 58.6, and 77.5%, respectively. The incidence of nodal
      involvement was 0% (0/10) in patients with grade 1 tumors, 57.1% (16/28) in those
      with grade 2 tumors, and 83.3% (35/42) in those with grade 3 tumors. Of the 57
      patients with lymph node metastasis determined sonographically, 50 had grade 2 or
      3 tumors that were histologically confirmed. The remaining seven patients with
      grade 1 tumors did not have involved nodes. Of the 23 patients without lymph node
      metastasis according to ultrasound examination, the incidence of lymph node
      metastasis in patients with grade 1, 2, and 3 tumors was 0, 16.7, and 50.0%,
      respectively. CONCLUSIONS: When used together, imaging and molecular procedures
      may offer improved identification of lymph node metastasis in patients with
      squamous cell carcinoma of the esophagus.

PMID- 12210025
TI  - Postoperative morbidity, mortality, and survival in lung cancer associated with
      idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Although postoperative morbidity and mortality rates in patients with
      lung cancer have decreased with advances in perioperative management, those
      patients with idiopathic pulmonary fibrosis (IPF) remain at a high risk of
      complication and death. The frequency of postoperative morbidity and mortality
      rates in patients with lung cancer who have IPF have seldom been reported,
      however. METHODS: A retrospective study of 711 patients with lung cancer who had
      undergone surgical resection was conducted. Medical records were retrospectively
      compared for factors that might affect postoperative morbidity and mortality in
      patients with and without IPF. RESULTS: Of the 711 patients with lung cancer, 53
      (7.5%) had IPF. The patients with IPF had pulmonary morbidity and mortality more
      frequently than those without IPF (26% versus 9.1%, P < 0.01; 8% versus 0.8%; P <
      0.01). The 5-year survival was 43% among patients with IPF and 64.2% among those
      without IPF. Overall survival in patients with IPF was significantly lower than
      in those without IPF (P < 0.01), but disease-free survival was similar in the
      groups. Thirty-five percent of the deaths (8 of 23) were not related to lung
      cancer in those patients with IPF, compared with 18% (35 of 199) of the deaths
      among those without IPF (P = 0.048). CONCLUSION: Patients with IPF showed
      markedly higher postoperative pulmonary morbidity and mortality than those
      without IPF. The survival rate of patients with IPF was lower because of
      pulmonary complications. Careful preoperative evaluation and perioperative
      management are required to achieve optimal surgical outcome in patients with lung
      cancer who have IPF.

PMID- 12210026
TI  - Desmopressin inhibits lung and lymph node metastasis in a mouse mammary carcinoma
      model of surgical manipulation.
AB  - BACKGROUND AND OBJECTIVES: Desmopressin (DDAVP) is a synthetic derivative of
      vasopressin with hemostatic and fibrinolytic properties that has been used during
      surgery in patients with bleeding disorders. Our aim was to investigate the
      effect of DDAVP on lung and lymph node metastatic cell colonization using a
      preclinical mouse mammary carcinoma model of subcutaneous tumor manipulation and
      surgical excision. METHODS: Female BALB/c mice bearing the highly aggressive F3II
      mammary carcinoma were subjected to repeated manipulations of primary tumors (0.5
      kg/cm(2) during 2 min), followed (or not) by surgical excision. DDAVP was
      administered intravenously 30 min before and 24 h after each manipulation or
      surgery, at a dose of 2 microg/kg. At the end of the experiment, mice were
      sacrificed and necropsied. RESULTS: Tumor manipulation induced dissemination to
      the axillary nodes and increased up to 6-fold the number of metastatic lung
      nodules. Perioperative treatment with DDAVP dramatically reduced regional
      metastasis. The incidence of lymph node involvement in manipulated animals was
      12% with DDAVP and 87% without treatment (P < 0.02). Histopathological analysis
      of axillary nodes from DDAVP-treated animals showed sinusal histiocytosis and no
      evidence of cancer cells. Metastatic lung nodules were also reduced about 65% in
      animals treated with DDAVP (P = 0.026). CONCLUSIONS: Our results suggest a
      potential clinical application of DDAVP in the management of breast cancer, as
      well as other aggressive solid tumors. DDAVP may be useful to reduce the risk of
      metastatic cell colonization both during and after surgical manipulation.

PMID- 12210027
TI  - Review of the clinical, histological, and molecular aspects of pancreatic
      endocrine neoplasms.
AB  - Pancreatic endocrine neoplasms (PENs) are rare tumors, and little is known about
      their genetic and chromosomal alterations. Elucidation of the molecular events
      involved in PEN carcinogenesis has been hindered by the fact that PENs have been
      considered a single disease entity. The emergence of novel molecular
      characterization strategies has, however, made it apparent that these lesions
      exhibit diverse molecular fingerprints, which will facilitate the precise
      delineation of PEN prognosis, histopathology, and carcinogenesis.

PMID- 12210029
TI  - Treatment of nonresectable proximal bile duct carcinoma using intraoperative
      radiotherapy combined with hepatojejunostomy.

PMID- 12210030
TI  - Surgical quality in trials of adjuvant cancer therapy.

PMID- 12210031
TI  - Outcomes after emergency surgery for gastric perforation or severe bleeding in
      patients with gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: Free perforation and major bleeding in patients with
      gastric cancer are rare but serious conditions with potentially dangerous
      effects. To clarify the clinicopathologic characteristics of patients with these
      conditions and to determine the optimum management, we reviewed 16 cases of
      perforation and 13 cases of major bleeding in patients with gastric cancer who
      required emergency surgery. METHODS: We compared the clinical and histologic
      features of the patients with perforation and those with bleeding. Cox's
      multivariate regression analysis was used to compare survival rates between
      patients who underwent single-step surgery or a two-step radical procedure,
      between patients with stage I or II and stage III or IV cancer, between patients
      who underwent complete (R0) and incomplete (R1 or R2) resection, and between
      patients with bleeding and those with perforation. RESULTS: Many of the patients
      had advanced disease. There were no significant differences in clinicopathologic
      findings or survival between patients with gastric perforation and those with
      major bleeding. Patients who had major bleeding tended to have larger cancers. In
      the univariate analysis, gastrectomy (vs. no gastrectomy), R0 (vs. R1 or R2)
      resection, and lower stage (vs. higher stage) were highly correlated with
      improved survival time. CONCLUSIONS: Overall, patients with gastric cancers who
      underwent emergency gastrectomy had a poor prognosis, but it was better than that
      of patients who could not have gastrectomy because of the prXesence of advanced
      cancer. However, the survival rate was excellent in patients with early-stage
      cancer who underwent complete (R0) resection. We recommend complete resection
      when possible.

PMID- 12210032
TI  - Predictors of nodal metastasis in salivary gland cancer.
AB  - OBJECTIVES: This study was conducted to determine clinical and histologic factors
      that would predict nodal metastasis in patients with major salivary gland cancer.
      METHODS: A retrospective study of 40 patients who underwent surgery, including
      neck dissection, for major salivary gland cancer between 1975 and 1997 was
      performed. Patient charts were reviewed, and clinical and pathologic data were
      extracted along with outcome. Predictive factors were identified and survival
      curves were obtained. RESULTS: Neck dissections were performed in 40 patients,
      which revealed histologic evidence of tumor in lymph nodes in 15 cases.
      Histologically proven metastasis was found in 16% of specimens from elective and
      73% of specimens from therapeutic neck dissection. Five-year overall and
      locoregional disease-free survival rates for histologically positive and negative
      groups were 40% versus 63% (P < 0.05) and 67% versus 69% (P = 0.59),
      respectively. Univariate analysis of the factors revealed that clinical evidence
      of nodal metastasis (P < 0.001) and high-grade cancer (P < 0.033) predicted
      histologic nodal involvement. Multivariate analysis revealed that only a positive
      neck examination was a significant predictive factor (OR = 31, 95%CI = 2.99-312).
      CONCLUSIONS: Our results suggest that clinical neck examination is a reliable
      predictor of regional metastasis in patients with major salivary gland cancer. In
      view of the low frequency of occult metastases, routine elective treatment of the
      neck is not recommended.

PMID- 12210033
TI  - Analysis of gene expression in Egr-1 transfected human fibrosarcoma cells.
AB  - BACKGROUND AND OBJECTIVES: It has been shown previously that transcription factor
      Egr-1 functions as a tumor suppressor gene. This study was conducted to
      investigate the possible mechanisms responsible for this function. METHODS: A
      cDNA microarray technique was applied to study differential gene expression
      between Egr-1-transfected cells and control-transfected cells. RESULTS: A number
      of genes differentially expressed were identified. Among 5,184 genes examined by
      cDNA microarray technique, 53 were up-regulated in Egr-1 transfected cells, and
      276 were down-regulated in Egr-1 transfected cells by at least two times or more;
      13 genes were independently confirmed by reverse transcription polymerase chain
      reaction (RT-PCR). Of these 13 genes, 11 were in agreement with cDNA microarrays
      in terms of gene expression levels. CONCLUSIONS: Egr-1 regulated almost every
      category of genes according to gene ontology system, and repressed more genes
      than it induced. The identification and further characterization of genes
      regulated by Egr-1 should provide valuable information to understand Egr-1 tumor
      suppressor action and the role of Egr-1 as a transcription factor in general.

PMID- 12210034
TI  - Establishment and characterization of OCUT-1, an undifferentiated thyroid cancer
      cell line expressing high level of telomerase.
AB  - BACKGROUND & OBJECTIVES: Undifferentiated thyroid cancer is one of the most
      aggressive human malignancies, and the prognoses that have been reported are
      extremely poor. A number of studies have described the clinicopathologic features
      of this tumor and analyzed its biologic background to explain the extraordinarily
      aggressive nature of the tumor. Still the mechanism of cellular aggressiveness in
      undifferentiated thyroid cancer is not yet fully understood. METHODS: We
      established and characterized an undifferentiated thyroid cancer cell line, OCUT
      1, derived from the surgical specimen obtained from a 74-year-old Japanese woman
      with advanced undifferentiated thyroid cancer. RESULTS: The cell line had already
      maintained over 100 passages and was stably cultured for more than a year. The
      cell line was observed to maintain not only its morphologic similarity to the
      primary cancer cells, but also its aggressive nature, including high
      proliferative activity, numerous genetic abnormalities, and cytokine production.
      Further, we have demonstrated the expression of telomerase activity in the cell,
      which could represent one of the responsible mechanisms for the cellular
      aggressiveness of this type of tumor. CONCLUSIONS: This cell line might be useful
      for further study concerning the correlation between telomerase activation and
      disease progression or anaplastic change in thyroid cancer.

PMID- 12210035
TI  - Genetic profiling of colon cancer.

PMID- 12210036
TI  - Radical resection of a malignant mesenchymoma with hypogastric artery
      transposition.

PMID- 12210037
TI  - Minimally invasive video-assisted thyroidectomy and lymphadenectomy for
      micropapillary carcinoma of the thyroid.

PMID- 12210038
TI  - Computer graphic to design the approach for resection of esthesioneuroblastoma.

PMID- 12210039
TI  - Reoperation combined with intraoperative hyperthermic intrathoracic perfusion
      chemotherapy for pleural recurrence of thymoma.

PMID- 12210040
TI  - Inhibition-based metabolic drug-drug interactions: predictions from in vitro
      data.
AB  - There has been a growing interest in predicting in vivo metabolic drug-drug
      interactions from in vitro systems. High-throughput screening methods aimed at
      assessing the potential of drug candidates for drug interactions are widely used
      in industry. However, at present, there is no consensus on methodologies that
      would yield reliable quantitative predictions, because a number of issues remain
      unsolved, such as estimations of inhibition constants in vitro and inhibitor
      concentration around the enzyme site in vivo. In the present review, different
      approaches to estimation of inhibitor concentration around the enzyme site are
      summarized; also, the problems associated with estimation of in vitro K(i) values
      due to incubation conditions and environment differences between in vitro and in
      vivo are presented. A new approach based on comparisons of in vitro and in vivo
      inhibition potencies by calculation of in vivo inhibition constants is discussed.
      Examples of predictions of in vivo drug interactions based on mechanism-based
      inactivation are described. Unresolved issues that would allow further refinement
      of existing prediction models are also evaluated.

PMID- 12210041
TI  - Distribution, metabolism, and excretion of a novel surface-active agent, purified
      poloxamer 188, in rats, dogs, and humans.
AB  - Purified poloxamer 188 (PP188) is a nonionic, block copolymer surfactant with
      hemorheologic, antithrombotic, and anti-adhesive properties. PP188 is being
      studied in phase III clinical trials in sickle cell disease and has been found to
      be well tolerated and has demonstrated benefit in ameliorating the effects of
      acute painful vasoocclusive crisis. The disposition of PP188 was studied in rats,
      dogs, and humans to establish a basis for understanding the safety parameters in
      support of clinical trials. PP188 was primarily distributed in extracellular
      water with little or no uptake by red blood cells, and had its highest
      concentrations in highly perfused tissues such as the kidney, liver, spleen,
      lymph nodes, and gastrointestinal tract. PP188 had no apparent effect on P450
      isozymes in vitro. Metabolism was limited (< 5% of dose) with a higher molecular
      weight copolymer being the only other material detected in plasma or urine. Renal
      clearance was the controlling route of clearance for PP188 from the body. The 48
      h intravenous infusion doses of PP188 were cleared in all species by
      approximately 1 week after the cessation of dose administration. PP188's
      disposition is a model for other nonionic block copolymers with similar physical
      and chemical properties.

PMID- 12210042
TI  - Physicochemical characterization of solid dispersions of carbamazepine formulated
      by supercritical carbon dioxide and conventional solvent evaporation method.
AB  - Solid dispersions of carbamazepine (CBZ) were formulated by supercritical fluid
      processing (SCP) and conventional solvent evaporation in polyethylene glycol
      (PEG) 8000 with either Gelucire 44/14 or vitamin E TPGS NF (d-alpha-tocopheryl
      PEG 1000 succinate). Formulations were evaluated by dissolution, scanning
      electron microscopy, powder X-ray diffraction, and differential scanning
      calorimetry, and excipient cytotoxicity in Caco-2 cells by MTS [3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H
      tetrazolium, inner salt] assay. CBZ release was enhanced from supercritical fluid
      treated CBZ and the CBZ/PEG 8000 (1:5), CBZ/PEG 8000/TPGS or Gelucire 44/14
      (1:4:1) solid dispersions. The radically altered morphologies of SCP samples seen
      by scanning electron microscopy suggested polymorphic change that was confirmed
      by the X-ray diffraction and differential scanning calorimetry. Disappearance of
      the characteristic CBZ melting peak indicated that CBZ was dissolved inside the
      carrier system. Polymorphic change of CBZ during SCP led to faster dissolution.
      Therefore, SCP provides advantages over solid dispersions prepared by
      conventional processes.

PMID- 12210043
TI  - Biochemical evidence for transcytotic absorption of polyaspartamide from the rat
      lung: effects of temperature and metabolic inhibitors.
AB  - Airway-to-perfusate polyhydroxyethylaspartamide (PHEA) absorption was studied in
      the isolated perfused rat lung at a reduced temperature and by the use of
      metabolic inhibitors, to kinetically clarify the mechanisms and cellular pathways
      of its active absorption. Fluorophore-labeled PHEA (F-PHEA; 7.4 kDa) was
      administered into the airways, and its absorption followed with time at 25
      degrees C and in the presence of 2,4-dinitrophenol (DNP), ouabain (OUA), monensin
      (MON), and nocodazole (NOC). Across-dose absorption profiles were analyzed using
      a kinetic model incorporating active (V(max,P) and K(m,P)) and passive (k(a,P))
      absorption from the pulmonary lung region alongside the competing, pulmonary-to
      bronchial mucociliary escalator (k(E)). The model was validated at 25 degrees C
      and a lack of perturbation on the k(a,P) and k(E) values for passively absorbed
      solutes confirmed by studying the disposition of sodium fluorescein and 4.4 kDa
      fluorescein isothiocyanate-labeled dextran. F-PHEA absorption was significantly
      suppressed at 25 degrees C, compared with 37 degrees C, because of a significant
      decrease in the value of the maximum rate of active absorption, V(max,P) (4.37 -
      > 0.67 microg/min; p < 0.05), whereas the carrier-affinity term, K(m,P), was
      statistically unchanged. F-PHEA's active absorption was also significantly
      inhibited by DNP (> or =0.5 mM), OUA (> or =50 microM), MON (> or =10 microM),
      and NOC (> or =1 microM), whereas these inhibitors had no significant effect on
      the values for k(a,P) and k(E). Thus, F-PHEA's pulmonary active absorption in the
      rat lung was temperature- and adenosine 5'-triphosphate-derived intracellular
      energy-dependent (DNP and OUA inhibition) and apparently mediated via
      transcytosis through cytoplasmic endosomes and microtubules (MON and NOC
      inhibition).

PMID- 12210044
TI  - Effect of glycine on pH changes and protein stability during freeze-thawing in
      phosphate buffer systems.
AB  - Previous studies have established that the selective precipitation of a less
      soluble buffer component during freezing can induce a significant pH shift in the
      freeze concentrate. During freezing of sodium phosphate solutions,
      crystallization of the disodium salt can produce a pH decrease as great as 3 pH
      units which can dramatically affect protein stability. The objective of our study
      was to determine how the presence of glycine (0-500 mM), a commonly used bulking
      agent in pharmaceutical protein formulations, affects the pH changes normally
      observed during freezing in sodium phosphate buffer solutions and to determine
      whether these pH changes contribute to instability of model proteins in
      glycine/phosphate formulations. During freezing in sodium phosphate buffers, the
      presence of glycine significantly influenced the pH. Glycine at the lower
      concentrations (< or = 50 mM) suppressed the pH decrease normally observed during
      freezing in 10 and 100 mM sodium phosphate buffer, possibly by reducing the
      nucleation rate of salt and thereby decreasing the extent of buffer salt
      crystallization. The presence of glycine at higher concentration (> 100 mM) in
      the sodium phosphate buffer resulted in a more complete crystallization of the
      disodium salt as indicated by the frozen pH values closer to the equilibrium
      value (pH 3.6). Although high concentrations of glycine can facilitate more
      buffer salt crystallization and these pH shifts may prove to be potentially
      damaging to the protein, glycine, in its amorphous state, can also act to
      stabilize a protein via the preferential exclusion mechanism.

PMID- 12210045
TI  - Effects of poly(ethylene glycol) on efflux transporter activity in Caco-2 cell
      monolayers.
AB  - Poly(ethylene glycol) (PEG) is an excipient commonly used in pharmaceutical
      formulations to increase the aqueous solubility of drugs intended for oral
      administration. High concentrations of PEG are often used to solubilize drug
      candidates for in vitro experiments in cell culture (e.g., Caco-2 cell
      permeability studies) and/or for in vivo pharmacokinetic and safety studies in
      animals. Although PEG is often deemed safe in these studies based on gross
      morphological studies, changes on a molecular level may be overlooked. The
      purpose of this study was to determine the possible effects of PEG on efflux
      transporter activity in Caco-2 cell monolayers, an in vitro model of the
      intestinal mucosa. In these studies, relatively high, yet clinically achievable,
      concentrations of PEG-300 did not significantly change the passive paracellular
      or transcellular permeation of model solutes across Caco-2 cell monolayers. More
      importantly, PEG-300 inhibited efflux transporter activity in Caco-2 cell
      monolayers, which is probably mediated by P-gp and/or MRP. Such PEG-induced
      inhibition of efflux transporter activity is most likely caused by changes in the
      microenvironment of the Caco-2 cell membranes, which perturbs the ability of
      these transporters to efflux substrates such as taxol and doxorubicin.

PMID- 12210046
TI  - A comparison of commonly used polyethoxylated pharmaceutical excipients on their
      ability to inhibit P-glycoprotein activity in vitro.
AB  - P-glycoprotein (P-gp), a multidrug resistance (MDR) protein encoded by the MDR1
      gene in humans, is responsible for the efflux of structurally diverse drugs.
      Previous studies in our laboratory have shown that excipients such as
      poly(ethylene)glycol (PEG)-300, Cremophor EL, and Tween 80 inhibit P-gp activity
      in Caco-2 cell monolayers. The objective of this study was to determine the
      effects of these excipients in an MDR1- transfected Madin Darby Canine Kidney
      (MDR1-MDCK) cell line and to compare the results with those obtained from Caco-2
      cells. The results presented herein show that PEG-300 (20%, v/v) causes almost
      complete inhibition of P-gp activity in both Caco-2 and MDR1-MDCK cell
      monolayers, whereas Cremophor EL (0.1%, w/v) and Tween 80 (0.05%, w/v) only
      partially inhibit P-gp activity in Caco-2 cells. Cremophor EL (0.1%, w/v) and
      Tween 80 (0.05%, w/v) were inactive as P-gp inhibitors in MDR1-MDCK cell
      monolayers. This inability of Tween 80 and Cremphor EL to inhibit P-gp activity
      in MDR1-MDCK cells may be related to differences in the interactions of the
      surfactants with these different cell membranes. PEG-induced changes in P-gp
      activity are probably related to changes in the fluidity of the polar head group
      regions of cell membranes.

PMID- 12210047
TI  - Ionizable drugs and pH oscillators: buffering effects.
AB  - It has been proposed that chemical pH oscillators may form a basis for periodic,
      pulsed drug delivery of weak acids and bases across lipophilic membranes.
      However, drugs have been shown to interfere with the ability of the chemical
      systems to oscillate, and rhythmic delivery of drugs by this means has been
      demonstrated only under constrained circumstances. Herein, we provide evidence
      that low concentrations of acidic drugs can attenuate and ultimately quench
      chemical pH oscillators, by a simple buffering mechanism. A model system
      consisting of the bromate-sulfite-marble pH oscillator in a continuous stirred
      tank reactor is used, along with acidic drugs of varying concentration and acid
      dissociation constant, pK(D). A published kinetic model for this oscillator is
      modified to account for the presence of acidic drug, and the results of this
      model are in qualitative agreement with the experimental results.

PMID- 12210048
TI  - Transmucosal delivery of testosterone in rabbits using novel bi-layer
      mucoadhesive wax-film composite disks.
AB  - Testosterone exhibits very low oral bioavailability because of its low aqueous
      solubility and extensive first-pass metabolism. The purpose of this study was to
      develop a novel bi-layer mucoadhesive wax-film composite (WFC), and to test the
      relative bioavailability of testosterone via the buccal route in rabbits. The
      release rate of testosterone from optimal WFCs (3/8-in. diameter) per unit
      surface area was 5.6 microg x cm(2) x mL(-1) x min(-1) and was zero-order. Bi
      layer WFCs (average weight of 14 +/- 2.6 mg and thickness of 186 +/- 34 microns)
      containing 4 mg of testosterone were applied to the buccal pouch of anesthetized
      New Zealand white rabbits. Rabbits (n = 3) injected intravenously had C(max) and
      area under the curve values of 1200 +/- 46 ng/mL, and 48,227 +/- 12,995 ng x
      min/mL, respectively. Rabbits (n = 3) dosed via the buccal pouch had C(max),
      T(max), and area under the curve values of 127 +/- 13 ng/mL, 200 +/- 35 min, and
      24,221 +/- 1543 ng x min/mL. The relative bioavailability for rabbits treated
      with the WFC was 50.2 +/- 3.2% with a coefficient of variation of 6.4%. It was
      concluded that these bi-layer mucoadhesive WFCs disks could deliver
      physiologically relevant amounts of insoluble drugs such as testosterone across
      the buccal mucosa.

PMID- 12210049
TI  - Micronization of insulin from halogenated alcohol solution using supercritical
      carbon dioxide as an antisolvent.
AB  - Insulin was precipitated from solution in 1,1,1,3,3,3-hexafluoro-2-propanol
      (HFIP) using supercritical carbon dioxide (CO2) as an antisolvent. Biosynthetic
      human insulin crystals were dissolved in HFIP and the solution was sprayed
      through an ultrasonic nozzle into supercritical CO2. The factors in the 2(3)
      factorial experimental design with a center point replicate included pressure
      (83.7 and 97.5 bar), solution concentration (15 and 30 mg/mL), and solution flow
      rate (2 and 4 mL/min). Temperature (37 degrees C), CO2 mass flow rate (137
      g/min), and volume of solution sprayed (20 mL) were held constant. High
      performance liquid chromatography, circular dichroism spectroscopy, infrared and
      Raman spectroscopy, scanning electron microscopy, dry powder size distribution
      analysis, thermogravimetric analysis, and atomic absorption spectroscopy were
      used to characterize the processed insulin powder. The processed insulin retained
      its potency, was slightly degraded chemically, and exhibited reversible
      structural changes. The precipitated powder consisted of physical aggregates of
      50-nm spheres. Through deagglomeration of these aggregates, it may be possible to
      obtain discrete uniform particles (1-5 microm) suitable for pulmonary therapy.
      Over the ranges of operating variables studied, the factors chosen for the
      experimental design had little effect on the product characteristics.

PMID- 12210050
TI  - Influence of excipients, drugs, and osmotic agent in the inner core on the time
      controlled disintegration of compression-coated ethylcellulose tablets.
AB  - The effect of excipient, drug, and osmotic agent loaded in the inner core tablet
      on the time-controlled disintegration of compression-coated tablet prepared by
      direct compression with micronized ethylcellulose was investigated. The
      excipients [spray-dried lactose, hydroxypropyl methyl cellulose, sodium starch
      glycolate, microcrystalline cellulose, different drugs (sodium diclofenac: model
      drug, salbutamol sulfate, and theophylline anhydrate) and osmotic agent (sodium
      chloride)] were used to formulate the composition of the inner core tablet. The
      result indicates that drug release from all the compression-coated tablets was
      characterized by a distinctive lag of time followed by a faster drug release,
      dependent on the types of excipient and drug, and osmotic agent used in the inner
      core tablet. Respectively, the lag of time was 8.5, 12.4, 14.6, or 15.8 h for
      spray-dried lactose, hydroxypropyl methyl cellulose, sodium starch glycolate, or
      microcrystalline cellulose-loaded inner core tablet, as compared with 16.4 h for
      an inner core made of sodium diclofenac alone. The direct-compressible excipients
      such as spray-dried lactose, sodium starch glycolate, and microcrystalline
      cellulose seemed not to illustrate a marked disintegration function to rapidly
      rapture the outer coating layer. The lag of time was only slightly shortened from
      16.4 to 14.6 h, >24 to 17.8 h, or >24 to 21.3 h for sodium diclofenac,
      theophylline anhydrate, or salbutamol sulfate incorporated with sodium starch
      glycolate into the inner core tablet, respectively, suggesting that sodium starch
      glycolate did not perform its superdisintegration. Once an osmotic agent of
      sodium chloride was incorporated into the inner core tablet, the lag of time for
      the compression-coated tablet was markedly shortened to <1 h, as compared with
      16.4 h for drug alone. The more the amount of sodium chloride added, the less the
      time of lag obtained. Osmotic pressure did have a key role in controlling the
      drug dissolution. The present result implies that osmotic function is more
      suitable than superdisintegration function in designing a compression-coated
      tablet with time-controlled disintegration.

PMID- 12210051
TI  - Conformational flexibility and hydrogen-bonding patterns of the neotame molecule
      in its various solid forms.
AB  - The conformational flexibility and the molecular packing patterns of the neotame
      molecule in its various crystal forms, including neotame monohydrate, methanol
      solvate, ethanol solvate, benzene solvate, and anhydrate polymorph G, are
      analyzed in this work. The Cerius2 molecular modeling program with the Dreiding
      2.21 force field was employed to calculate the most stable conformations of
      neotame molecules in the gaseous state and to analyze the conformations of the
      neotame molecule in its various crystal forms. Using graph set analysis, the
      hydrogen bond patterns of these crystal forms were compared. The neotame molecule
      takes different conformations in its crystal forms and in the free gaseous state.
      Cerius2 found 10 conformers with lower conformational energies than those in the
      actual crystal structures, which represent an energetic compromise. The
      relatively large differences between the energies of the conformers indicate the
      necessity for rewriting or customizing the force field for neotame. The hydrogen
      bonding patterns of the neotame methanol and ethanol solvates are identical, but
      different from those of the other three forms, which also differ from each other.
      The neotame molecule in its various crystal forms takes different conformations
      that differ from those in the gaseous state because of the influence of crystal
      packing. The intramolecular ring, S5, is present in all the crystal forms. The
      following hydrogen bonding patterns occur in some of the crystal forms: diad, D;
      intramolecular rings, S(6) and S(7); chains, C(5) and C(6); and an intermolecular
      ring, R2(2)(12).

PMID- 12210052
TI  - Noncovalent dimerization of paclitaxel in solution: evidence from electrospray
      ionization mass spectrometry.
AB  - Paclitaxel, a unique antimitotic chemotherapy agent that inhibits cell division
      by binding to microtubules and prevents them from "depolymerizing," has received
      widespread interest because of its efficacy in fighting certain types of cancer,
      including breast and ovarian cancer. Paclitaxel undergoes aggregation at
      millimolar concentrations in both aqueous media and solvents of low polarity
      (mimicking hydrophobic environments). Its aggregation may have impact on its
      aqueous stability and its ability to stabilize microtubules. Here, we
      investigated the dimerization phenomenon of paclitaxel by electrospray ionization
      mass spectrometry (ESI-MS). Paclitaxel dimers were stable in solutions of
      acetonitrile/aqueous ammonium acetate (80/20) and aqueous sodium
      acetate/acetonitrile (92/8 or 95/5) at various pH values. Additional experiments
      using solution-phase hydrogen/deuterium exchange were employed to ascertain
      whether or not the observed dimers were formed in solution or as an artifact of
      the ESI process by ion-molecule reaction. The evidence supports formation of the
      dimer in solution, and the approach used can be extended to investigation of
      other types of drug-drug interactions.

PMID- 12210053
TI  - Isolation and characterization of metabolites of centpropazine in rat liver,
      intestine, and red blood cell homogenates.
AB  - The potential sites for metabolism of centpropazine (CPZ) (an antidepressant)
      were evaluated in male Sprague-Dawley rats. The isolation and identification of
      the major metabolites formed in the presence of rat liver S9 fraction, intestine,
      and red blood cells under aerobic conditions were performed using high
      performance liquid chromatography and electrospray ionization mass spectrometry.
      CPZ was found to be extensively metabolized to seven possible metabolites by
      liver S9 fraction in the presence of a nicotinamide adenine dinucleotide
      phosphate generating system at 37 degrees C. Both intestinal wall and red blood
      cells were also found to metabolize the compound. This metabolite structure was
      confirmed by comparison with that of its synthetic standard. The drug was stable
      in intestinal contents. On the basis of our finding, we propose the in vitro
      metabolic pathways for CPZ.

PMID- 12210054
TI  - Design, development, physicochemical, and in vitro and in vivo evaluation of
      transdermal patches containing diclofenac diethylammonium salt.
AB  - In this study, matrix-type transdermal patches containing diclofenac diethylamine
      were prepared using different ratios of polyvinylpyrrolidone (PVP) and
      ethylcellulose (EC) by solvent evaporation technique. The drug matrix film of PVP
      and EC was casted on a polyvinylalcohol backing membrane. All the prepared
      formulations were subjected to physical studies (moisture content, moisture
      uptake, and flatness), in vitro release studies and in vitro skin permeation
      studies. In vitro permeation studies were performed across cadaver skin using a
      modified diffusion cell. Variations in drug release profiles among the
      formulations studied were observed. Based on a physicochemical and in vitro skin
      permeation study, formulation PA4 (PVP/EC, 1:2) and PA5 (PVP/EC, 1:5) were chosen
      for further in vivo experiments. The antiinflammatory effect and a sustaining
      action of diclofenac diethylamine from the two transdermal patches selected were
      studied by inducing paw edema in rats with 1% w/v carrageenan solution. When the
      patches were applied half an hour before the subplantar injection of carrageenan
      in the hind paw of male Wistar rats, it was observed that formulation PA4
      produced 100% inhibition of paw edema in rats 12 h after carrageenan insult,
      whereas in the case of formulation PA5, 4% mean paw edema was obtained half an
      hour after the carrageenan injection and the value became 19.23% 12 h after the
      carrageenan insult. The efficacy of transdermal patches was also compared with
      the marketed Voveran gel and it was found that PA4 transdermal patches produced a
      better result as compared with the Voveran gel. Hence, it can be reasonably
      concluded that diclofenac diethylamine can be formulated into the transdermal
      matrix type patches to sustain its release characteristics and the polymeric
      composition (PVP/EC, 1:2) was found to be the best choice for manufacturing
      transdermal patches of diclofenac diethylamine among the formulations studied.

PMID- 12210055
TI  - Examination of the flow rheological and textural properties of polymer gels
      composed of poly(methylvinylether-co-maleic anhydride) and
      poly(vinylpyrrolidone): rheological and mathematical interpretation of textural
      parameters.
AB  - The purpose of this study was to mathematically characterize the effects of
      defined experimental parameters (probe speed and the ratio of the probe diameter
      to the diameter of sample container) on the textural/mechanical properties of
      model gel systems. In addition, this study examined the applicability of
      dimensional analysis for the rheological interpretation of textural data in terms
      of shear stress and rate of shear. Aqueous gels (pH 7) were prepared containing
      15% w/w poly(methylvinylether-co-maleic anhydride) and poly(vinylpyrrolidone)
      (PVP) (0, 3, 6, or 9% w/w). Texture profile analysis (TPA) was performed using a
      Stable Micro Systems texture analyzer (model TA-XT 2; Surrey, UK) in which an
      analytical probe was twice compressed into each formulation to a defined depth
      (15 mm) and at defined rates (1, 3, 5, 8, and 10 mm s(-1)), allowing a delay
      period (15 s) between the end of the first and beginning of the second
      compressions. Flow rheograms were performed using a Carri-Med CSL(2)-100
      rheometer (TA Instruments, Surrey, UK) with parallel plate geometry under
      controlled shearing stresses at 20.0 degrees +/- 0.1 degrees C. All formulations
      exhibited pseudoplastic flow with no thixotropy. Increasing concentrations of PVP
      significantly increased formulation hardness, compressibility, adhesiveness, and
      consistency. Increased hardness, compressibility, and consistency were ascribed
      to enhanced polymeric entanglements, thereby increasing the resistance to
      deformation. Increasing probe speed increased formulation hardness in a linear
      manner, because of the effects of probe speed on probe displacement and surface
      area. The relationship between formulation hardness and probe displacement was
      linear and was dependent on probe speed. Furthermore, the proportionality
      constant (gel strength) increased as a function of PVP concentration. The
      relationship between formulation hardness and diameter ratio was biphasic and was
      statistically defined by two linear relationships relating to diameter ratios
      from 0 to 0.4 and from 0.4 to 0.563. The dramatically increased hardness,
      associated with diameter ratios in excess of 0.4, was accredited to boundary
      effects, that is, the effect of the container wall on product flow. Using
      dimensional analysis, the hardness and probe displacement in TPA were
      mathematically transformed into corresponding rheological parameters, namely
      shearing stress and rate of shear, thereby allowing the application of the power
      law (eta = kgamma(n)) to textural data. Importantly, the consistencies (k) of the
      formulations, calculated using transformed textural data, were statistically
      similar to those obtained using flow rheometry. In conclusion, this study has,
      firstly, characterized the relationships between textural data and two key
      instrumental parameters in TPA and, secondly, described a method by which
      rheological information may be derived using this technique. This will enable a
      greater application of TPA for the rheological characterization of pharmaceutical
      gels and, in addition, will enable efficient interpretation of textural data
      under different experimental parameters.

PMID- 12210056
TI  - Apoptosis, necrosis, or whatever: how to find out what really happens?
AB  - There is no doubt that thorough knowledge of apoptotic cell death is of paramount
      importance for many areas of current research. Despite many available ways of
      detecting apoptotic cell death, the analysis of apoptosis reveals considerable
      conceptual and technological problems. In this issue of The Journal of Pathology,
      Grogan and colleagues offer an interesting study, in which they present a
      promising model system for investigating the spatio-temporal events of initiation
      and progression of apoptosis (and other forms of cell death). The confusing
      complexity of results based on parallel experiments in this paper might be partly
      due to technical variability or insufficiency; more likely, however, this
      provides evidence that most if not all approaches thought to be 'specific' for
      apoptotic cell death address different aspects of cell death, have different
      sensitivities and specificities, and are rather complementary than redundant.
      Grogan and colleagues provide an excellent demonstration of the uncertainties and
      ambiguities which result from basically all currently available technologies,
      yielding, even in one system, results which are partly confusing, because they
      are partly contradictory. This situation is typical for cell death analysis at
      present-not only in the cartilage field.

PMID- 12210057
TI  - In vitro model for the study of necrosis and apoptosis in native cartilage.
AB  - Apoptosis plays a role in everything from early development to ageing and in a
      host of disease states. Studying this important process in the in vivo state is
      critical, to understand its varied role and to open further avenues of
      therapeutic intervention. The present paper presents an ex vivo bovine articular
      cartilage model to study apoptotic and necrotic processes following acute injury.
      Ex vivo bovine articular cartilage was assessed 1, 3 and 6 days following holmium
      : YAG laser treatment (780 mJ). Markers to visualize cell viability, caspase-3
      activity, changes in mitochondrial membrane potential and the degree of DNA
      fragmentation (TUNEL assay) were used alone or in various combinations. Standard
      histology and transmission electron microscopy (TEM) were also performed for a
      more comprehensive assessment. A significant progression (p < 0.05) of
      ethidium/caspase-3-positive signal depth at day 3 preceded a significant increase
      (p < 0.05) in TUNEL signal depth by day 6. The mitochondrial matrix marker CMXRos
      was shown to provide an alternative to calcein-AM for assessing cell viability.
      The identification of chondrocyte apoptosis morphology by TEM was not conclusive.
      Nevertheless, TEM revealed that cells which were clearly necrotic also stained
      positively for TUNEL, thus indicating the risk of using TUNEL alone for the
      assessment of apoptosis. The model described here allows the rapid, spatial and
      temporal determination of cell viability and of apoptotic and necrotic processes
      in whole-tissue specimens after acute injury, and permits study of the balance
      between these events. The assessment of healthy and diseased cartilage and of the
      effects of surgical, pharmaceutical or in vitro intervention are immediate
      applications of these protocols. Moreover, this model may be useful for the study
      of key mechanisms involved in apoptosis or for the establishment of other markers
      of apoptosis.

PMID- 12210059
TI  - Allotype imbalance or microsatellite mutation in low-grade soft tissue sarcomas
      of the extremities in adults.
AB  - The ability to repair DNA double-strand breaks is essential to maintain
      chromosomal stability. Virtually all soft tissue sarcomas contain chromosomal
      instabilities, including clonal aberrations and cytogenetic aberrations. However,
      the relevance of DNA-dependent protein kinase (DNA-PK) in the pathogenesis of
      soft tissue sarcoma has not been clarified. The main aim of this work is to
      compare the prognostic impact of genotypic imbalance in low-grade soft tissue
      sarcomas of the extremities, and to correlate this with the translational level
      of DNA-PK. This study investigated 28 adult low-grade malignant spindle cell
      tumours of the extremities, predominantly fibrosarcomas, for loss of
      heterozygosity (LOH) and microsatellite mutation on flanking regions of each DNA
      PK subunit, with identical immunophenotypes. Twelve different polymorphic markers
      flanking the specific loci of three subunits comprise the genetic map of DNA-PK,
      at 22q13, 2q35, and 8q11. Translational activity was also analysed by western
      blot and conventional immunohistochemistry. The overall sarcoma 5-year survival
      rate was 61.7%. LOH was identified in the specific coding region of DNA-PK in
      39.29% for the DNA-PK catalytic subunit (cs), 17.86% for Ku70, and only 7.14% for
      Ku80. A positive LOH for DNA-PKcs was shown to be a significant factor for poor
      survival (log rank test p = 0.0160). Immunoreactivity and immunoblot results
      correlated with the loss of DNA-PKcs allotype in soft tissue sarcoma (Fisher's
      exact test p = 0.0037). Ku70 and DNA-PKcs were almost identical in terms of
      immunoreactivity. In conclusion, whereas microsatellite mutation seems an
      uncommon event during the evolution of low-grade fibrosarcoma of the extremities
      in adults, the loss of DNA-PKcs defines a biologically more aggressive subset.

PMID- 12210058
TI  - Loss of heterozygosity for the NF2 gene in retinal and optic nerve lesions of
      patients with neurofibromatosis 2.
AB  - Individuals affected with the neurofibromatosis 2 (NF2) cancer predisposition
      syndrome develop specific ocular lesions. To determine whether these lesions
      result from altered NF2 gene expression, microdissection and PCR were used to
      investigate 40 ocular lesions from seven eyes of four NF2 patients for LOH, with
      markers that flank the NF2 gene on chromosome 22q. NF2 protein (merlin)
      expression was also evaluated in these lesions, using immunohistochemistry.
      Retinal hamartoma was observed in all seven eyes, including one with combined
      pigment epithelial and retinal hamartoma (CPERH). Retinal tufts were present in
      four eyes (three patients), retinal dysplasia in two eyes (two patients), optic
      nerve neurofibroma in one eye, iris naevoid hyperplasia in two eyes (two
      patients) and pseudophakia in all eyes. Markers were informative in three
      patients (six eyes from three unrelated families). One patient was non
      informative due to prolonged decalcification. All retinal and optic nerve, but
      not iris lesions, demonstrated consistent LOH for the NF2 gene. Merlin was not
      expressed in the retina, optic nerve, or iris lesions. These results suggest that
      inactivation of the NF2 gene is associated with the formation of a variety of
      retinal and optic nerve lesions in NF2 patients.

PMID- 12210060
TI  - Phenotypic characterization of mononuclear and multinucleated cells of giant cell
      reparative granuloma of small bones.
AB  - Four cases of giant cell reparative granuloma (GCRG) of small bones were analysed
      in order to determine the pathogenesis of the lesion and the nature of the
      component mononuclear and multinucleated cells. In cell cultures, giant cells
      formed a non-proliferating homogeneous population which expressed features
      characteristic of the osteoclast phenotype, including leucocyte common antigen,
      CD68, vitronectin receptor, and tartrate-resistant acid phosphatase. The giant
      cells were capable of lacunar resorption and their activity was inhibited by
      calcitonin. In addition to numerous macrophage-like cells, some of which
      expressed osteoclast phenotypic characteristics, there were also mononuclear
      stromal cells which proliferated in culture and were alkaline phosphatase
      positive; these cells expressed receptor activator of NF-kappaB ligand (RANKL)
      and were capable of supporting human osteoclast formation from circulating
      precursors in vitro. These findings suggest that the osteoclast-like giant cells
      in GCRG of small bones are formed from monocyte/macrophage-like osteoclast
      precursors which differentiate into osteoclasts under the influence of
      mononuclear osteoblast-like stromal cells.

PMID- 12210061
TI  - Transcription and alternative splicing of telomerase reverse transcriptase in
      benign and malignant breast tumours and in adjacent mammary glandular tissues:
      implications for telomerase activity.
AB  - Telomerase activity was determined in 15 breast cancers, 24 benign breast
      lesions, and 36 breast tissues adjacent to benign or malignant tumours. A
      positive TRAP (telomeric repeat amplification protocol) signal was detected in
      67% of carcinomas and 29% of benign tumours. In five of ten cases, non-invaded
      breast tissues adjacent to telomerase-positive carcinomas also displayed
      telomerase activity. Conversely, in peritumoural specimens adjacent to benign
      lesions, telomerase activity was never detected. To investigate the regulatory
      mechanisms of telomerase activity in breast tissues, the expression of telomerase
      subunits was assessed, as well as the presence of alternatively spliced variants
      of human telomerase reverse transcriptase (hTERT). The presence of the hTERT full
      length transcript appeared necessary for telomerase activity in breast
      carcinomas. Specifically, all telomerase-positive carcinomas expressed the hTERT
      full-length message, together with different combinations of alternatively
      spliced variants, whereas in telomerase-negative cancers, the hTERT full-length
      transcript was not detectable, or its abundance was markedly lower than that of
      alternatively spliced variants. Results obtained in benign tumours and normal
      tissues surrounding carcinomas instead showed that the presence of hTERT full
      length transcript was not sufficient to determine telomerase activity. These
      findings suggest that in non-neoplastic tissues there are other mechanisms that
      suppress telomerase activity downstream from hTERT transcription and mRNA
      splicing and that such mechanisms have been lost during neoplastic
      transformation.

PMID- 12210062
TI  - Diagnosis of chronic atrophic gastritis by morphometric image analysis. A new
      method to overcome the confounding effect of the inflammatory infiltrate.
AB  - The risk of gastric cancer increases with the severity of gastric mucosal
      atrophy. Atrophy is a 'loss of properly specialized glands'. These glands may be
      substituted by metaplastic cells and by interstitial fibrosis, or displaced by an
      inflammatory infiltrate. Agreement among pathologists for the diagnosis of
      atrophy is poor (kappacoefficient < 0.4), probably because inflammatory
      infiltrate can confound the identification of gland loss. The aim of this study
      was to evaluate interstitial fibrosis by image analysis, and thereby overcoming
      the confounding effect of the inflammatory infiltrate. Gastric biopsies of 40
      controls (20 children and 20 adults) and 111 patients with chronic atrophic
      gastritis were examined. Patients underwent another biopsy a year later. Gastric
      sections were examined by conventional histology (updated Sydney system) and
      image analysis to detect collagen and non-collagen fibres. There were no
      significant intra- or inter-operator differences in the evaluation by image
      analysis of fibre content in either controls or patients. In both controls and
      patients, the mean percentage of collagen fibres was lower in the gastric body
      (9%) than in the antrum (10%). In the antrum it was 14%, 17% and 20% in patients
      with mild, moderate and severe atrophy, respectively. A year later, histology
      showed that the grade of atrophy had decreased in 42%, probably due to the
      regression of inflammation, and increased in 10% of cases, but interstitial
      fibrosis (expressed as collagen fibre content) was practically unchanged. The use
      of image analysis of gastric biopsies appears to be a reliable method with which
      to measure interstitial fibrosis, even in the presence of an inflammatory
      infiltrate. This study highlights the difference between 'real gastric atrophy',
      where glands are replaced by collagen fibres, and 'apparent gastric atrophy',
      where glands are displaced by an inflammatory infiltrate.

PMID- 12210063
TI  - Distinct promoter hypermethylation of p16INK4a, CDH1, and RAR-beta in intestinal,
      diffuse-adherent, and diffuse-scattered type gastric carcinomas.
AB  - Hypermethylation of CpG islands in gene promoters is associated with silencing of
      various tumour suppressor genes. Recent studies of colorectal and gastric
      carcinomas have defined a CpG island methylator phenotype (CIMP), which involves
      the targeting of multiple genes by promoter hypermethylation. In this study,
      methylation-specific polymerase chain reaction (PCR) was performed to study
      methylation of CpG islands in the promoters of the p16(INK4a), cadherin 1 (CDH1),
      and retinoic acid receptor-beta (RAR-beta) genes in 45 gastric carcinomas and to
      investigate whether CDH1 and RAR-beta promoter hypermethylation is associated
      with CIMP-positive gastric carcinoma. CpG island hypermethylation of the
      p16(INK4a), CDH1, and RAR-beta promoters was detected in 12 (27%), 26 (58%), and
      24 (53%) of the 45 gastric carcinomas, respectively. Hypermethylation of the
      p16(INK4a) promoter was more common in intestinal type than in diffuse type
      gastric carcinomas (p = 0.0023; Fisher's exact test) and was inversely associated
      with p53 mutations (p = 0.0225; Fisher's exact test). However, CDH1 and RAR-beta
      promoter hypermethylation was observed more frequently in diffuse-scattered type
      gastric carcinoma than in other types (intestinal and diffuse-adherent types) (p
      = 0.0175 and p = 0.0335, respectively; Fisher's exact test) and was not
      associated with p53 mutation status. Moreover, hypermethylation of the CDH1 and
      RAR-beta promoters occurred concordantly (p < 0.0001; Fisher's exact test). These
      results suggest that at least two types of promoter methylation status are
      involved in the development of the intestinal (p16(INK4a) promoter
      hypermethylation) and diffuse-scattered types (CDH1 and RAR-beta promoter
      hypermethylation) of gastric carcinoma.

PMID- 12210064
TI  - Protection of the Peyer's patch-associated crypt and villus epithelium against
      methotrexate-induced damage is based on its distinct regulation of proliferation.
AB  - The crypt and villus epithelium associated with Peyer's patches (PPs) is largely
      spared from methotrexate (MTX)-induced damage, compared with the non-patch (NP)
      epithelium. To assess the mechanism(s) preventing damage to the PP epithelium
      after MTX treatment, epithelial proliferation, apoptosis, and cell functions were
      studied in a rat-MTX model. Small intestinal segments containing PPs were excised
      after MTX treatment. Epithelial proliferation and apoptosis were assessed by
      detection of incorporated BrdU and cleaved caspase-3, respectively. Epithelial
      functions were determined by the expression of cell type-specific gene products
      at mRNA and protein level. Before and after MTX treatment, the number of BrdU
      positive cells was higher in PP crypts than in NP crypts. BrdU incorporation was
      diminished in NP crypts, while in PP crypts incorporation was hardly affected. In
      PP and NP crypts, similar and increased levels of cleaved caspase-3-positive
      cells were observed after MTX. The enterocyte markers, sucrase-isomaltase, sodium
      glucose co-transporter 1, glucose transporters 2 and 5, and intestinal and liver
      fatty acid binding protein, were down-regulated after MTX in NP epithelium but
      not in PP epithelium. In contrast, expression of the goblet cell markers, Muc2
      and trefoil factor 3, and the Paneth cell marker, lysozyme, was maintained after
      MTX in both PP and NP epithelium. In conclusion, as MTX-induced apoptosis was
      similar in PP and NP crypts, the protection of the PP epithelium seems to be
      based on differences in the regulation of epithelial proliferation. Enterocyte
      function in the PP epithelium was unaffected by MTX treatment. Goblet and Paneth
      cell function was maintained in both NP and PP epithelium.

PMID- 12210065
TI  - The expression of E-cadherin and catenins in colorectal tumours from familial
      adenomatous polyposis patients.
AB  - Familial adenomatous polyposis patients (FAP) harbour a germline mutation of the
      adenomatous polyposis coli gene (APC), and APC mutations are early events in the
      development of sporadic colorectal neoplasms. The APC protein interacts with beta
      catenin and gamma-catenin and APC mutations are believed to play a role in the
      altered levels of beta-catenin in colorectal tumours. Immunohistochemical studies
      have shown changes in the expression and distribution of E-cadherin and catenins
      in sporadic colorectal neoplasms. This study assessed the expression and
      distribution of E-cadherin and catenins in colorectal neoplasms and non
      neoplastic mucosa from FAP patients. The expression and cellular distribution of
      E-cadherin and catenins were studied by immunohistochemistry in 61 adenomas, five
      carcinomas, and non-neoplastic mucosa from 18 FAP patients. mRNA levels in the
      carcinomas were studied by in situ hybridization. The expression of E-cadherin
      and catenins was increased in over 80% of the adenomas, with evident cytoplasmic
      immunoreactivity. There was increased expression of E-cadherin and catenin in the
      carcinomas, with a notable increase in the levels of mRNA, in comparison with the
      non-neoplastic mucosa.

PMID- 12210066
TI  - Neuropilin-2 is a novel marker expressed in pancreatic islet cells and endocrine
      pancreatic tumours.
AB  - Neuropilin-2 (NP-2) is a cell surface transmembrane protein originally
      characterized as a receptor for the type 3 semaphorins, and more recently for a
      number of vascular endothelial growth factor (VEGF) isoforms. NP-2 expression has
      been recently localized to a subset of neuroendocrine cells in the
      gastrointestinal tract. The aim of this study was to define the expression
      pattern of NP-2 in normal pancreatic islets and to determine the utility of NP-2
      expression as a diagnostic marker of pancreatic endocrine tumours. Paraffin
      embedded tissue sections from 30 endocrine pancreatic tumours (EPTs) and from
      normal pancreas were immunostained with a rabbit polyclonal antibody generated
      towards NP-2. Nineteen of the tumours were hormonally functional (nine
      insulinomas, nine gastrinomas, and one glucagonoma). The NP-2 staining pattern
      was correlated with islet cell hormone expression. In addition, NP-2 expression
      was evaluated in other normal neuroendocrine tissues and neuroendocrine
      neoplasms. In normal pancreas, NP-2 stained a distinct subset of islet cells
      situated primarily at the islet periphery. Double immunohistochemical staining
      revealed co-localization with glucagon-expressing cells. Moderate to strong NP-2
      staining was present in 27 of 30 EPTs. Serial staining of the pancreatic tumours
      with insulin, gastrin, glucagon, pancreatic polypeptide (PP) or somatostatin did
      not reveal a distinct pattern of co-localization. NP-2 expression was not
      detected in neuroendocrine cells outside the gastroenteropancreatic system, or in
      their corresponding neoplasms, except for focal staining in one bronchial
      carcinoid tumour. In conclusion, the vast majority of EPTs examined expressed NP
      2, suggesting its utility as a diagnostic marker for these tumours. The function
      of NP-2 in islet cell biology or tumourigenesis remains to be elucidated.

PMID- 12210067
TI  - Detection of N-myc amplification by FISH in immature areas of fixed
      neuroblastomas: more efficient than Southern blot/PCR.
AB  - N-myc amplification is a major prognostic factor in neuroblastomas and is
      systematically investigated by Southern blot or polymerase chain reaction (PCR).
      A retrospective study of N -myc amplification has been carried out using
      fluorescence in situ hybridization (FISH) in 97 fixed neuroblastomas. For each
      tumour, FISH was performed on the area that contained the most immature
      neuroblasts. Among these 97 neuroblastomas, 16 were amplified and 12 were not
      interpretable. FISH was not interpretable in six cases. All neuroblastomas with N
      myc amplification detected by Southern blot/PCR were amplified with FISH, except
      three that were not interpretable. Four tumours that were not interpretable in
      Southern blot/PCR contained more than five copies of N-myc by FISH: one was
      aneuploid and three were truly amplified, containing more than ten copies of N
      myc. Among these three patients, two died in a short time of their tumours. Ten
      cases were not amplified by Southern blot/PCR and showed more than five copies by
      FISH: four were aneuploid and two showed heterogeneous amplification, with a few
      cells clearly amplified whereas most were not. Four cases were amplified, of
      which two patients died of their tumours. This study confirms that when applied
      to the most immature areas of fixed neuroblastomas, FISH displayed a higher
      sensitivity than molecular techniques (p < 0.001) and could detect heterogeneous
      amplification. FISH could therefore become an important complementary procedure
      in assessing prognosis in neuroblastomas.

PMID- 12210068
TI  - Spitz naevi may express components of the plasminogen activation system.
AB  - The plasminogen activation (PA) system is involved in the process of invasion and
      metastasis. Its major components are urokinase (uPA) and tissue-type plasminogen
      activator (tPA), plasminogen activation inhibitor type 1 and 2 (PAI-1 and PAI-2)
      and a receptor for urokinase (uPAR). In this study, the expression of plasminogen
      activation components in Spitz naevi was compared with that in common and
      dysplastic naevi on the one hand and primary cutaneous melanomas on the other.
      Spitz naevi had melanocytic positivity for uPA in 0% (0/36), tPA in 30% (6/20),
      PAI-1 in 10% (3/35), PAI-2 in 40% (8/21) and uPAR in 60% (13/21) of cases. This
      far exceeded the expression found in common (n = 25) and dysplastic (n = 15)
      naevi, which only showed melanocytic positivity for PAI-2 (20% and 15%
      respectively) and in one dysplastic naevus also for uPAR. This was much (for most
      components significantly) less than the proportion of primary melanomas with
      tumour cell positivity, which was 30% (11/38) for uPA, 80% (19/24) for tPA, 75%
      (28/38) for PAI-1, 80% (19/24) for PAI-2 and 80% (19/24) for uPAR. The main
      findings of this study are that Spitz naevi, firstly, may express plasminogen
      activator (tPA), inhibitors and the receptor of the PA system, but in a much
      smaller proportion than cutaneous melanomas; and secondly, do not express
      urokinase, whereas some of the melanomas do. uPA positivity may therefore be
      suggestive of melanoma. However, overlapping staining results imply that the PA
      system has limited value in the differential diagnosis between Spitz naevus and
      primary melanoma. As serine protease components are expressed, Spitz naevi may
      use this proteolytic machinery to accomplish matrix degradation, although in a
      more restricted, possibly transient manner than melanomas.

PMID- 12210069
TI  - p63 immunoreactivity in lung cancer: yet another player in the development of
      squamous cell carcinomas?
AB  - The p63 protein, a member of the p53 family of nuclear transcription factors, is
      characterized by different capabilities of transactivating reporter genes,
      inducing apoptosis, and functioning as dominant-negative agent. This study
      evaluated the prevalence and prognostic implications of p63 immunoreactivity in
      221 patients with stage I non-small cell lung carcinoma (NSCLC) and in 57
      patients with stage I-IV neuroendocrine tumours (NET). The results were
      correlated with the tumour proliferative fraction, the accumulation of p53
      protein, and with patient survival. p63 immunoreactivity was seen in 109/118
      squamous cell carcinomas, 15/95 adenocarcinomas, 2/2 adenosquamous carcinomas,
      4/6 large cell carcinomas, 9/20 poorly differentiated NET, and 1/37 typical and
      atypical carcinoids (p < 0.001). Furthermore, the prevalence of p63
      immunoreactive cells increased progressively from pre-neoplastic and pre-invasive
      lesions to invasive squamous cell carcinomas. In these latter tumours, but not in
      adenocarcinomas, p63 immunoreactivity correlated directly with the tumour
      proliferative fraction (p = 0.028), and inversely with the tumour grade (p =
      0.004). No relationship was found with p53 protein immunoreactivity or the other
      clinico-pathological variables examined. Although p63 is likely to be involved in
      the development of pulmonary squamous cell carcinoma, it does not carry any
      prognostic implication for NSCLC patients.

PMID- 12210070
TI  - Chromosome 14q LOH in localized clear cell renal cell carcinoma.
AB  - The progression of a malignant tumour is understood to be the result of the
      accumulation of multiple genetic aberrations. As up to 14% of organ-confined
      renal cell carcinomas will recur after surgery, tumour clones with metastatic
      potential must already be present in some of these localized tumours. The
      association of 14q LOH with high-grade tumours and advanced tumour stage suggests
      an important role for the gene in tumour progression. Chromosome 14q LOH has been
      analysed in microdissected specimens from 130 organ-confined (UICC TNM stage 1
      and 2) clear cell renal cell carcinomas using three microsatellite markers
      (D14S588, D14S617, GATA136B01). Tumours were classified as 14q LOH or not on the
      basis of LOH at one or more of the markers. The allelic imbalance ratio was used
      to determine both LOH and LOH proportion and the association between LOH and
      mortality, tumour size, histological grade and growth kinetics, measured by
      quantification of nucleolar organizer regions, was analysed. 14q LOH was present
      in 35.4% of informative cases at marker D14S588, 24.4% at D14S617, 36.4% at
      GATA136B01 and 39.5% for any one of the three markers. The mean 14q LOH
      proportion was 0.24 (range 0.009-0.80). LOH proportion correlated significantly
      with tumour size, AgNOR score and histological grade. It was also significantly
      associated with disease-specific mortality; (hazard ratio 1.22; 95% CI 1.02-1.45;
      p = 0.039). LOH proportion did not remain significant after adjusting for tumour
      size (hazard ratio 0.98; 95% CI 0.76-1.27; p = 0.90). These results indicate that
      the proportion of cells with 14q LOH in the tumour is associated with tumour
      aggressiveness; while this is not an independent predictor of survival, it may
      have some utility as a marker of latent metastatic potential.

PMID- 12210071
TI  - Patterns of chromosomal aberrations in urinary bladder tumours and adjacent
      urothelium.
AB  - Bladder cancer is often characterized by recurrent and multifocal growth, and
      tumours are frequently accompanied by precancerous alterations of the surrounding
      urothelium. These findings have led to the hypothesis that cells from areas of
      genetically aberrant but morphologically non-cancerous or even unremarkable
      mucosa may be the source of bladder carcinomas. Fluorescence in situ
      hybridization (FISH) was performed using ten probes targeting five different
      chromosomes that are known to be frequently altered in bladder cancer (centromere
      1, 8, 9, 11, 17 and 1p36, 8p23, 9p21, 11q13, 17p13) on paraffin-embedded tissue
      sections of 11 superficial bladder cancers. Copy number changes of the tumours
      were compared to those in the urothelium adjacent to the tumour. Eleven of 11
      (100%) tumours and eight of 11 (73%) samples of adjacent urothelium showed copy
      number changes of at least one chromosome. The occurrence of similar patterns of
      chromosomal aberrations in the tumours and their associated urothelium supports
      the hypothesis of a clonal relationship. It is concluded that FISH analysis
      targeting five different chromosomes is more sensitive than conventional
      histology for distinguishing between neoplastic and normal cells of the
      urothelium.

PMID- 12210072
TI  - Heterogeneous expression of Ku70 in human tissues is associated with
      morphological and functional alterations of the nucleus.
AB  - Ku70 is a subunit of DNA-protein kinase complex and involved in diverse
      intranuclear events including the repair of double-stranded DNA breaks. Ku70 is
      rich in the interphase nucleus of cultured cells. In human tissues, however, the
      distribution of Ku70 has not yet been systematically examined. To characterize
      the difference of Ku70 distribution between cells of human tissues and cultured
      cells, the expression of Ku70 was examined in various normal and neoplastic human
      tissues by immunohistochemistry and immunoblot. In addition, the role of Ku70 in
      the cellular response against ionizing radiation (IR) was analysed in fibroblasts
      after exposure to 5 Gy IR and apoptotic indices were examined in Ku70
      overexpressed fibroblasts from an ataxia telangiectasia patient and in normal
      fibroblasts, before and after irradiation. In contrast to cultured cells, Ku70
      was not detected in some interphase cells of human tissues and was distributed
      heterogeneously, even in the same nucleus. Ku70 expression was strikingly low in
      terminally differentiated cells such as neutrophils, eosinophils, glomerular
      capillary endothelial cells and fibroblasts, and was absent in spermatids. In
      spermatocytes, Ku70 was tightly integrated with chromosome filaments, unlike
      other somatic cells under mitosis. After exposure to IR, Ku70 expression was not
      increased in ataxia telangiectasia fibroblasts, but was significantly increased
      in normal fibroblasts. Most of the increased Ku70 was of soluble nuclear protein
      fraction. Furthermore, overexpression of Ku70 increased radiation resistance both
      in ataxia telangiectasia fibroblasts and normal fibroblasts. The presented data
      indicate that the distribution of Ku70 in cells of human tissues is closely
      associated with the cell cycle, cellular differentiation, nuclear shape and the
      process of repair of DNA damage caused by IR.

PMID- 12210073
TI  - Comment on a recent paper and editorial on the subject of dysplasia
      classification.

PMID- 12210074
TI  - Functional allelic loss detected at the protein level in archival human tumours
      using allele-specific E-cadherin monoclonal antibodies.
AB  - Immunohistochemical analysis has been used to show that expression of the
      homophilic cell-to-cell adhesion molecule, E-cadherin, is frequently altered in
      human cancers, including gastric and breast carcinoma. Besides genetic down
      regulation, structural mutations such as in-frame deletions of exon 8 and exon 9
      were frequently found; these may affect the binding of monoclonal antibodies used
      for immunohistochemical analysis. In this study it was found that antibodies HECD
      1 and E9, two monoclonal antibodies often used in E-cadherin immunoanalysis,
      react with epitopes present at least in part in exon 8 and exon 9, respectively.
      This study generated and characterized a mutation-specific monoclonal antibody, E
      cad delta 8-1, reacting with the mutant protein lacking exon 8 but not with the
      wild-type molecule. By using E-cad delta 8-1 and HECD-1, it was possible
      separately to analyse the immunoreactivity of mutant and normal E-cadherin
      proteins, respectively, in an allele-specific manner in archival material. A
      similar analysis was performed using E9 and the previously characterized mutation
      specific antibody E-cad delta 9-1. Typically, in gastric and breast cancer
      harbouring E-cadherin splice site gene mutations, the mutant proteins were
      expressed but the wild-type protein was not detected in malignant tissues. These
      results indicate that variant-specific monoclonal antibodies can be used to
      identify differentially expressed E-cadherin proteins. For immunohistochemical
      analysis of E-cadherin, at least two different monoclonal antibodies should be
      used to exclude alterations of the epitopes resulting in failure to detect a
      mutant protein.

PMID- 12210075
TI  - Analysis of the progression of fibroepithelial tumours of the breast by PCR-based
      clonality assay.
AB  - Fibroadenoma and phyllodes tumour of the breast are both fibroepithelial tumours.
      Although progression to epithelial malignancy has been described, the behaviour
      of most fibroadenomas is benign. Phyllodes tumours, on the other hand, can
      display locally destructive growth and can even metastasize. A relationship
      between the two tumours has been suggested in the literature. This study
      investigated the clonality of both the stroma and the epithelium of these
      fibroepithelial tumours and attempted to construct a model in which fibroadenoma
      can progress in both an epithelial and a stromal direction. Fibroadenomas (n=25)
      and phyllodes tumours (n=12) were selected for analysis. Tissue was
      microdissected and analysed for clonality using a polymerase chain reaction (PCR)
      based assay targeted at an X-linked polymorphic marker, the human androgen
      receptor gene (HUMARA). Nineteen fibroadenomas and nine phyllodes tumours could
      be analysed. Normal-appearing epithelium, hyperplastic epithelium, and stroma
      removed from fibroadenomas were polyclonal. As expected, carcinoma in situ (CIS)
      removed from four fibroadenomas was monoclonal. Three areas of apparent stromal
      expansion within fibroadenoma were monoclonal, suggesting stromal progression.
      Mostly, the stroma of phyllodes tumours was monoclonal and the epithelium
      polyclonal. In two cases, however, the epithelium seemed to be monoclonal,
      whereas in three other cases the stromal component was polyclonal. These findings
      indicate that fibroadenoma can progress in an epithelial direction to CIS and in
      a stromal direction to phyllodes tumour.

PMID- 12210076
TI  - Expression of trefoil peptides (TFF1, TFF2, and TFF3) in gastric carcinomas,
      intestinal metaplasia, and non-neoplastic gastric tissues.
AB  - Trefoil factor family (TFF) domain peptides consist of three members that play a
      role in intestinal mucosal defence and repair, and in tumourigenesis. The role of
      the three TFF members in the gastric carcinogenesis cascade remains poorly
      defined. This study examined seven gastric cell lines, 50 gastric cancers and
      their adjacent non-cancer tissues, and tissues from 40 non-cancer patients, in
      order to elucidate the chronology of TFF expression in various stages of gastric
      carcinogenesis. TFF expression was determined by RT-PCR, immunohistochemistry,
      and western blot. Aberrant expression of TFF1, TFF2, and TFF3 was frequently
      detected in gastric cell lines. Specifically, TFF1 was detected in all non-cancer
      patients, but was detected in only 50% of gastric cancer and 66% of adjacent
      normal tissues. TFF2 expression was demonstrated in 87.5% of non-cancer patients,
      34% of gastric carcinomas, and 58% of adjacent non-cancer tissues. There was a
      significant correlation between TFF1 and TFF2 expression in gastric cancer and
      adjacent non-cancer tissues (p<0.001). By contrast, TFF3 was detected in 25% of
      non-cancer patients and showed a predilection for areas with intestinal
      metaplasia (p=0.005). Sixty-two per cent of gastric cancers and 24% of
      neighbouring non-cancer tissues showed TFF3 expression. Immunoreactivity against
      TFF3 was demonstrated in goblet cells of intestinal metaplasia and within the
      cytoplasm and nuclei of tumour cells. Progressive loss of TFF1 and TFF2, together
      with the induction of TFF3, is likely to be involved in the early stage of the
      multi-step gastric carcinogenesis pathway.

PMID- 12210077
TI  - Expression of 4C8 antigen, a novel transendothelial migration-associated molecule
      on activated T lymphocytes, in inflammatory bowel disease.
AB  - Recruitment of peripheral leukocytes to intestine is an essential process for
      intestinal inflammation. This study examined the localization of a novel
      molecule, 4C8 antigen, in inflammatory bowel disease; this molecule is involved
      in the transendothelial migration of T lymphocytes. Surgical specimens of human
      intestine were obtained from nine patients with ulcerative colitis, 13 with
      Crohn's disease, and eight controls. Immunohistological staining was performed
      using antibodies against 4C8 antigen, and CD3, CD4, CD8, CD20, CD68, CD45RA,
      CD45RO, CD11a, and CD62 (E- and P-selectin) by the peroxidase method.
      Immunological double staining was subsequently performed for the same specimens
      stained with anti-4C8 antibody using the alkaline phosphatase method. In normal
      controls, 4C8-positive cells were mainly found in lamina propria. 4C8-positive
      cells were increased in lamina propria and submucosa of specimens with Crohn's
      disease. Accumulation of 4C8-positive cells surrounding CD62-positive vessels was
      found in the submucosa of specimens with inflammatory bowel disease, but not in
      controls. Immunohistological double staining revealed that the major subsets of
      4C8-positive cells were positive for CD3, CD4, CD45RO, and CD11a. 4C8-positive
      cells in human intestine belong to the subset of helper/inducer memory T cells
      newly recruited from the peripheral pool. Inhibition of the 4C8-ligand system
      could have potentially uses in the treatment of inflammatory bowel disease.

PMID- 12210078
TI  - FK409 inhibits both local and remote organ damage after intestinal ischaemia.
AB  - In addition to localized tissue injury, intestinal ischaemia-reperfusion (I/R)
      leads to remote organ damage, in particular to the lungs. Given that nitric oxide
      (NO) can attenuate I/R-induced tissue injury in many situations, this study
      evaluated the effects of the NO donor, FK409, on leukocyte adhesion in the
      microcirculation of the intestinal villus and also assessed pulmonary tissue
      damage after intestinal I/R injury. PVG rats were subjected to 30 min intestinal
      ischaemia and a sub-group of animals received the NO donor FK409 (10 mg/kg; i.v.)
      both 30 min prior to ischaemia and 30 min post-reperfusion. The intestinal
      mucosal surface was visualized via an incision made in an exteriorized ileal
      segment and leukocyte adhesion in the villous microcirculation was determined by
      in vivo microscopy. Total and differential leukocyte counts from peripheral blood
      were evaluated. Lungs were removed at the end for histological assessment. Six
      out of ten untreated I/R animals failed to survive the 2 h reperfusion period,
      whereas all ten FK409-treated animals survived. I/R induced a significant
      increase in villous leukocyte adhesion of untreated I/R animals (p<0.001) and
      this was significantly decreased by FK409 treatment (p<0.001). The total
      leukocyte count was significantly decreased in untreated I/R animals (p<0.001)
      and this primarily resulted from a reduction in circulating neutrophil numbers.
      This effect was not observed in FK409-treated animals. Collapsed alveoli,
      thickened interstitial walls, and a dense neutrophilic infiltrate were apparent
      in the lungs of untreated I/R animals, whereas lung histology was normal in FK409
      treated animals. In conclusion, FK409 prevented mortality, significantly reduced
      villous leukocyte adhesion, maintained circulating leukocyte numbers, and
      prevented pulmonary tissue injury following intestinal I/R. FK409 may therefore
      be of value in reducing both local and remote tissue damage and improving outcome
      in situations where intestinal I/R injury is obligatory, such as small bowel
      transplantation.

PMID- 12210079
TI  - Genetic progression in sporadic endometrial and gastrointestinal cancers with
      high microsatellite instability.
AB  - This study selected a series of 136 MSI-H (microsatellite instability at high
      frequency) gastric, colorectal, and endometrial carcinomas combining
      immunohistochemical analysis for hMLH1 or hMSH2 gene products and microsatellite
      study. The clinico-pathological profile of all tumours was correlated with the
      overall instability rates at coding and non-coding repeats, in order to clarify
      the role and the mutation timing of seven target genes (TGFbetaRII, IGFIIR, BAX,
      hMSH3, hMSH6, CHK1, and BRCA2) in the progression of an MSI-H neoplasm.
      Regardless of the primary site, the results confirm a model of oncogenesis in
      which inactivation of hMLH1, or less frequently hMSH2, may initiate a pathway
      culminating in a progressive accumulation of frameshifts in coding region (CDR)
      microsatellites. Comparing gastrointestinal and endometrial tumours,
      significantly lower levels of microsatellite instability at both coding and non
      coding repeats were observed. Among gastric and colorectal tumours, the detection
      of small shortening within Bat-26 and Bat-25 markers defines a subgroup of MSI-H
      gastrointestinal tumours invariably characterized by early stage at diagnosis. In
      these tumours, mutations of TGFbetaRII or BAX genes precede frameshifts in the
      other tested genes. The analysis of correlations between the mutational and
      clinico-pathological profiles of advanced gastrointestinal tumours revealed that
      the higher levels of microsatellite instability at both coding and non-coding
      repeats were not associated with a more advanced clinico-pathological stage or a
      less favourable outcome. A significant association was observed between a low
      number of CDR frameshifts and the presence of lymph-node metastasis in advanced
      gastrointestinal tumours. The existence of advanced MSI-H tumours with more
      aggressive behaviour and a 'mild mutator phenotype' could be explained by
      hypothesizing an overlapping of different mechanisms of tumourigenesis, including
      both the mutator and the suppressor pathways; this should be tested by further
      studies.

PMID- 12210080
TI  - Different expression of hepatitis B surface antigen between hepatocellular
      carcinoma and its surrounding liver tissue, studied using a tissue microarray.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide
      and is highly associated with chronic liver disease, including hepatitis B viral
      infection. In order to study the association between hepatitis B virus (HBV)
      infection and HCC development, tissue microarrays were used to detect the
      expression of hepatitis B surface antigen (HBsAg) in 194 HCCs and their
      surrounding liver tissues, using anti-HBsAg monoclonal antibody. The results
      showed that the expression of HBsAg is significantly lower in tumour tissue than
      in non-tumour tissue. Among the 138 cases with positive serum HBsAg, expression
      of HBsAg was more frequently detected in non-tumour tissue (103 cases, 75%) than
      in tumour tissue (11 cases, 8%). RT-PCR and Southern blot analysis were performed
      to explore the mechanism of the decreased expression of HBsAg in tumour cells.
      The RT-PCR results showed that absence or decreased expression of the HBV S gene
      was detected in 3/15 (20%) and 6/15 (40%) HCCs, respectively. Integration of HBV
      in 23 pairs of HCCs and their matched non-tumour liver tissues was studied by
      Southern blot. The results showed that the integrated HBV S gene sequence was
      detected in 19/23 tumours (83%) and 1/23 non-tumour tissues (4%), whereas the
      free replicative virus form was observed in 3/23 tumours (13%) and 14/23 non
      tumour tissues (61%). These findings suggest that HBsAg-negative results in
      tumour tissues were directly related to HBV DNA insertion and provide new
      insights into the involvement of HBsAg in hepatocarcinogenesis.

PMID- 12210081
TI  - Lack of in vivo blockade of Fas- and TNFR1-mediated hepatocyte apoptosis by the
      hepatitis C virus.
AB  - In vitro data have shown that the hepatitis C virus (HCV) core protein binds to
      protein members of the tumour necrosis factor receptor (TNFR) superfamily. Since
      this interaction could be relevant to HCV persistence and oncogenesis, this study
      assessed whether HCV may interfere with the apoptotic cascade in vivo. Apoptosis
      (by TUNEL) and Fas and TNFR1 expression (by immunohistochemistry) were scored in
      the liver of 60 chronic hepatitis C patients. Results were compared with the
      liver disease grading and staging scores and the HCV replication level in serum
      and liver. Apoptotic hepatocytes were stained in 29 cases. Fas was expressed in
      35 cases and TNFR1 in 21, 15 patients (25%) being negative for both receptors.
      Overall, the numbers of TUNEL-, Fas- and TNFR-positive hepatocytes did not
      correlate with the extent of intrahepatic CD8+ T-lymphocyte infiltration, the
      grading and staging of liver disease, or the serum or liver HCV RNA levels.
      Furthermore, when patients expressing either Fas or TNFR1 were stratified
      according to serum HCV RNA levels, cases with detectable hepatocyte apoptosis had
      higher HCV viraemias. In conclusion, an HCV-mediated, in vivo blockade of
      hepatocyte apoptosis via the Fas- or TNFR1-dependent pathways seems unlikely.

PMID- 12210082
TI  - Genetic and epigenetic alterations of the INK4a-ARF pathway in
      cholangiocarcinoma.
AB  - The INK4a-ARF locus, located on chromosome 9p21, encodes two cell-cycle
      regulatory proteins, p16(INK4a) and p14(ARF), acting through the Rb-CDK4 and p53
      pathways. To study the contribution of each pathway in the tumourigenesis of
      cholangiocarcinoma, the alterations of p14(ARF), p16(INK4a), p53, and pRb were
      analysed. After microdissection, DNAs from 51 cholangiocarcinomas were analysed
      by methylation-specific PCR (MSP), restriction-enzyme related polymerase chain
      reaction (RE-PCR), microsatellite analysis, mRNA expression, and DNA sequencing.
      Immunohistochemistry of p14(ARF), p16(INK4a), p53, and pRb was also performed.
      Promoter methylation of p14(ARF) was found in 13/51 cases (25%) and p16(INK4a)
      showed aberrant promoter methylation in 39/51 cases (76%) which correlated with
      loss of mRNA transcription. Two tumours (4%) had homozygous deletion of the INK4a
      ARF locus. Specific mutations of both exons were not detected. p14(ARF)
      inactivation appeared in the context of an unmethylated p16(INK4a) promoter in
      eight of 13 cases (61%) of the carcinomas methylated at p14(ARF). Mutations of
      p53 were found in 19 of 51 tumours (37%), and four of them (21%) harboured
      p14(ARF) inactivation. The pRb protein was detected in 30/51 (59%) tumours
      examined. The absence of pRB protein did not correlate with any of the examined
      parameters. Alterations of the INK4a-ARF locus, pRB or p53 status could not be
      established as independent prognostic factors in these tumours. These findings
      indicate that the INK4a-ARF locus is frequently inactivated in cholangiocarcinoma
      of the liver and occurs independently of the status of p53 or pRb.

PMID- 12210083
TI  - Mucin gene expression in intraductal papillary-mucinous pancreatic tumours and
      related lesions.
AB  - Intraductal papillary-mucinous tumours (IPMTs) of the pancreas are heterogeneous
      proliferations characterized by a malignant potential. The molecular mechanisms
      underlying the tumourigenesis process are not well understood. Recently, it has
      been shown that IPMTs secreting the mucin antigen MUC2 have a better prognosis,
      but the complete pattern of MUC gene expression has not yet been established. The
      aims of this study were to evaluate the mucin gene expression in 57 IPMTs and
      eight related lesions surgically resected and to relate MUC gene expression to
      the histological diagnosis. In situ hybridization (ISH) was performed in 28 cases
      with probes specific for the MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, and
      MUC7 genes. An immunohistochemical analysis was carried in all 65 cases and in 90
      conventional ductal adenocarcinomas of the pancreas using MUC1, MUC2, and MUC5AC
      antibodies. IPMTs of adenoma (dysplasia) type exhibited high expression of MUC2
      (93%), MUC5AC (97%), and, to a lesser extent, of MUC4 (71%), all of which were
      also observed in colloid carcinomas associated with IPMTs. In contrast, IPMTs
      with simple hyperplasia, intraductal oncocytic papillary neoplasms, and pyloric
      glandular adenomas exhibited little or no expression of MUC2. The mucin
      expression profile supports the existence of two types of invasive tumour
      associated with IPMTs: a colloid and an ordinary form. The latter shows a pattern
      similar to the conventional ductal adenocarcinomas with a loss of MUC2 and a gain
      of MUC1 and has a greater tendency to metastasize. In conclusion, the altered
      expression of mucin, characteristic of IPMT of adenoma type and of colloid
      carcinomas, may contribute to the better clinical outcome of these neoplasms,
      compared to conventional pancreatic ductal adenocarcinomas.

PMID- 12210084
TI  - Induction of PDX-1-positive cells in the main duct during regeneration after
      acute necrotizing pancreatitis in rats.
AB  - Pancreatic regeneration involves two pathways; proliferation and differentiation
      of pancreatic progenitor cells, which probably exist in pancreatic ductal
      epithelium, and replication of pre-existing differentiated acinar, islet, and
      ductal epithelial cells. During pancreatic development, differentiated cells
      arise from the ductal progenitor cells expressing the pancreatic/duodenal
      homeobox-1 (PDX-1) homeodomain transcription factor. The aims of this study were
      to characterize cell proliferation and differentiation during regeneration after
      acute necrotizing pancreatitis and to evaluate the role of PDX-1-positive stem
      cells. Necrotizing pancreatitis was induced in rats by retrograde intraductal
      infusion of sodium taurocholate. Cell types were classified into five categories:
      main, large, and small ductal epithelial cells, tubular complexes and acinar
      cells. Each category was scored using a 5-bromo-2'-deoxyuridine (BrdU) labelling
      index (LI) at various time points after induction of pancreatitis. Tissue
      sections were also immunostained for PDX-1 to determine the source of pancreatic
      stem cells. Acinar necrosis was observed at 24 h after induction of pancreatitis
      and most lobules were filled with tubular complexes on day 5. Subsequently, newly
      formed acinar cells were observed on day 7, but the lobular architecture returned
      to normal appearance on day 28. Proliferation started in the main and large ducts
      at 24 h; marked mitotic activity was evident in small ductal epithelial cells and
      tubular complexes on day 3, and in acinar cells on day 7. At 24 h after induction
      of pancreatitis, epithelial cells of the main duct with PDX-1-positive nuclei
      were greatly increased, simultaneously with the peak LI of BrdU. These results
      suggest that regeneration after necrotizing pancreatitis involves proliferation
      and differentiation of pancreatic progenitor cells, and that ductal epithelial
      cells with PDX-1-positive nuclei may contribute to the differentiation of
      pancreatic stem cells in the main duct.

PMID- 12210085
TI  - Altered expression of connexins 26 and 43 in Sertoli cells in seminiferous
      tubules infiltrated with carcinoma-in-situ or seminoma.
AB  - The expression of connexins (cx) 26 and 43 in testis infiltrated with carcinoma
      in-situ (CIS) or seminoma was examined to gain insight into the relationship
      between aberrant gap junctional communication and spermatogenic impairment in the
      neoplastic testis. In uninvolved tubules with normal spermatogenesis, cx43
      immunostaining was localized to the Sertoli-Sertoli junctional complex and cx26
      was absent. In contrast, infiltrated tubules with spermatogonial arrest or CIS
      only were negative for cx43, but displayed strong intracytoplasmic Sertoli cell
      staining for cx26. The Sertoli cells in these tubules re-expressed cytokeratin 18
      (ck18), signifying a reversion to a less differentiated state. Western blot
      analysis for cx43 revealed a single immunoreactive band at 43 kD (normal
      spermatogenesis) and three bands at 43, 41, and 39 kD (impaired spermatogenesis
      with CIS or seminoma). For cx26, a doublet band at 26/28 kD (normal
      spermatogenesis) and an additional doublet band at 52/54 kD (impaired
      spermatogenesis with CIS or seminoma) were observed. The altered expression of
      cx26 and cx43 in Sertoli cells in testes infiltrated with CIS or seminoma
      suggests that a derangement in intercellular communication between Sertoli cells
      and between Sertoli cells and germ cells may play a role in the resulting
      spermatogenic impairment and possibly in the proliferation and neoplastic
      progression of CIS cells.

PMID- 12210086
TI  - Significance of loss of heterozygosity of the RB1 gene during tumour progression
      in well-differentiated liposarcomas.
AB  - Tumour progression can be investigated in liposarcomas showing a transition from
      a low-grade well-differentiated (WD) to a high-grade dedifferentiated (DD)
      variant. As RB1 gene alterations are common defects in sarcomas, this study
      examined the frequency of RB1 loss of heterozygosity (LOH) in a group of 14 well
      differentiated liposarcomas (WDLs) and 17 well-differentiated/dedifferentiated
      liposarcomas (WD/DDLs), using a microdissection approach (PALM laser pressure
      catapulting) that allows the two histological components to be separated for
      polymerase chain reaction (PCR) analysis. In addition, RB1 protein expression and
      the Mib1 proliferation index were determined by immunohistochemistry and
      interphase FISH was performed with an RB1 probe at 13q14. By the use of four
      intragenic polymorphic RB1 markers (introns 1, 17, 20, and 25) for PCR, allelic
      losses were found only in the DD parts, but never in the pure WDLs or in the WD
      components of the WD/DDLs investigated. Furthermore, DD areas characterized by a
      heterogeneous RB1 protein expression pattern (35-65% immunopositivity), as
      compared with 90-100% RB1 positivity in WD areas, showed a marked increase in
      Mib1 proliferation index (19.6% versus 1.8% in WD areas; p<0.001). Interphase
      fluorescence in situ hybridization (FISH) detected a higher RB1-LOH rate in the
      DD components of WD/DDLs. Considering the different detection sensitivities of
      the three methodologies, it is concluded that loss of RB1 function already begins
      in the WDL, and that the tumour cell population with RB1-LOH starts prevailing in
      the tumour mass during progression of a WDL.

PMID- 12210087
TI  - Gene expression of TrkC (NTRK3) in human soft tissue tumours.
AB  - TrkC is a member of the Trk family of tyrosine kinase receptors and plays an
      important role in the development and maintenance of neural tissues. Although a
      variety of non-neuronal tissues have also been shown to express TrkC, the status
      of TrkC in soft tissue tumours has been poorly investigated, except for a small
      fraction of tumours including congenital/infantile fibrosarcoma characterized by
      an ETV6-NTRK3 (also known as Tel-TrkC) fusion gene. To broaden knowledge about
      the TrkC status in human neoplasms, the expression of TrkC transcripts was
      assessed in 51 soft tissue tumours of variable lines of differentiation by
      reverse transcription-polymerase chain reaction (RT-PCR), using primer sets
      flanking their extracellular domain, the tyrosine kinase domain, and the
      intracellular domain of a truncated variant (Trunc 1) described previously. In 44
      of the 51 tumours, TrkC transcripts, including alternatively spliced isoforms,
      were detected. The truncated transcripts (Trunc 1) were co-expressed in 40 of the
      44 tumours and were expressed in one tumour without native TrkC gene expression.
      In two of the remaining six tumours, part of the sequence coding the tyrosine
      kinase domain of TrkC appeared to be truncated. Using a 3' rapid amplification of
      cDNA ends (3'RACE) method, another truncated isoform (Trunc 2) was isolated from
      one of the tumours, in which the TrkC transcript was terminated with a novel 160
      base pair sequence. This truncated isoform was identified in nine of the 51
      tumours examined by RT-PCR using primers for Trunc 2. There was no clear
      correlation between the types of TrkC isoforms detected and histological types or
      grades of the tumours. These results suggest that human soft tissue tumours
      widely express TrkC, irrespective of their cellular lineage, morphology, and
      biological behaviour. Dysregulated TrkC expression may enhance overgrowth or
      transformation of various mesenchymal cells.

PMID- 12210088
TI  - Multiple complementary transcripts of pCMa1, a novel gene located at chromosome
      11p15.1-2, and melanocytic cell transformation.
AB  - The cDNA clone pCMa1 (0.45 kb) is one of the 12 novel cDNAs, previously
      identified when comparing RNA expression profiles of melanocytes, naevus cells,
      and non-metastatic melanoma cells. This clone did not reveal a unique long open
      reading frame. The pCMa1 gene localized to the distal, telomere proximal region
      on the short arm of chromosome 11.p15.1-2. Northern blot analyses with single
      stranded cRNA probes revealed the presence of various complementary pCMa1
      transcripts of different lengths, which are not enriched in the poly(A)(+) RNA
      fraction. The arbitrarily defined plus strand (used as a probe) mainly hybridized
      to 0.45 kb and 4.0 kb minus transcripts in total RNA samples, and the minus
      strand (used as a probe) hybridized to a major plus transcript of 4.0 kb. By RNA
      in situ hybridization, the highest levels of the plus transcripts were observed
      in melanocytic naevi (12/12), particularly in congenital naevi, whereas normal
      skin melanocytes (12/12) were negative. pCMa1 plus transcripts were detected in
      naevus cell nests (100%) near the dermo-epidermal junction. Expression, however,
      diminished to some extent in the deeper parts of the melanocytic naevi. Although
      most of the cutaneous primary melanoma lesions (11/15) showed detectable, but
      variable levels of plus transcripts of pCMa1 in the papillary to reticular
      dermis, not more than 10% of the melanoma cells were positive. The majority of
      melanoma metastases (6/7) were negative, while the positive lesion originated
      from a patient with a positive primary melanoma. Furthermore, plus transcripts
      were present in the nuclei of non-metastatic melanoma cells in culture, whereas
      metastatic cells showed elevated expression both in the nucleus and in the
      cytoplasm. Briefly, the data show transient up-regulation of pCMa1 in neoplastic
      progression of melanocytic cells, with peak levels occurring during naevus
      stages, and suggest that pCMa1 is a molecular marker in melanocytes for the early
      changes from the proliferating phenotype to malignant transformation.

PMID- 12210089
TI  - Vascular endothelial growth factor (VEGF) is expressed by neoplastic Hodgkin-Reed
      Sternberg cells in Hodgkin's disease.
AB  - Vascular endothelial growth factor (VEGF) is involved in tumour angiogenesis, an
      important process for the growth and metastatic potential of solid tumours.
      Numerous studies have demonstrated up-regulation of VEGF at both mRNA and protein
      level in various tumours and a correlation with advanced stage and prognosis has
      been demonstrated in some cases. Limited information exists about its role in
      lymphoid malignancies and in particular, Hodgkin's disease. The present study
      examined the immunohistochemical expression of VEGF using the monoclonal antibody
      VG1 in a series of 61 cases of Hodgkin's disease, including both classical
      Hodgkin's disease and the nodular lymphocyte predominance variant, and correlated
      these results with microvessel density, using an anti-CD31 monoclonal antibody.
      In 41 cases (70.6%) of classical Hodgkin's disease and one of the three cases of
      nodular lymphocyte predominance Hodgkin's disease, the neoplastic Reed-Sternberg
      and Hodgkin cells expressed VEGF. The staining observed was cytoplasmic, either
      diffuse or with a focal paranuclear distribution. Macrophages were always
      positive, while reactive lymphocytes showed occasional positivity. A variable
      amount of strong extracellular staining was also observed in the tissue stroma
      and intravascular plasma staining was prominent. There was no statistically
      significant relationship between VEGF expression and the subtype of Hodgkin's
      disease or microvessel density. In vitro studies using the Reed-Sternberg cell
      lines L428 and KM-H2 were also performed in both normoxia and hypoxia and VEGF
      protein production was assessed by flow cytometry (FACS), immunoassay of cell
      culture supernatant, and RT-PCR. Analysis by FACS demonstrated a subset of cells
      in both cell lines reacting with VG1 and analysis of secreted VEGF (pg/ml per
      1x10(6) cells) in cell culture supernatant confirmed the normoxic production in
      both cell lines and significant hypoxic induction (p<0.005). Additionally, both
      cell lines expressed VEGF mRNA, as demonstrated using the RT-PCR method. In
      conclusion, neoplastic cells express VEGF in Hodgkin's disease, as is the case in
      solid tumours, and this expression may be induced by hypoxia. The presence of
      VEGF in reactive macrophages and in the extracellular matrix might facilitate
      tumour progression.

PMID- 12210090
TI  - Detection of Epstein-Barr virus genome within thymic epithelial tumours in
      Taiwanese patients by nested PCR, PCR in situ hybridization, and RNA in situ
      hybridization.
AB  - Epstein-Barr virus (EBV) is known to be associated with a variety of tumours,
      including Burkitt's lymphoma, nasopharyngeal carcinoma, and some carcinomas of
      other organs with similar lymphoepithelioma-like features. The association
      between EBV and thymic epithelial tumours is inconclusive, as reports in this
      regard are not entirely consistent and the methods employed are of different
      sensitivity and specificity. This study examined 78 thymomas and 21 thymic
      carcinomas in Taiwanese patients, to detect the viral genome at both DNA and RNA
      levels. The tissue blocks were first screened by nested polymerase chain reaction
      (PCR) targeting on the first tandem internal repeats. The positive cases were
      further submitted for viral localization by in situ PCR insitu hybridization
      (ISH) and Epstein-Barr-encoded RNA-1 (EBER-1) ISH. None of the thymomas showed a
      detectable EBV genome. Eight thymic carcinomas were positive for EBV by nested
      PCR, of which six displayed nuclear signals within the tumour cells by in situ
      PCR ISH and/or RNA ISH, one displayed signals within the lymphocytes, and one
      showed no discernible in situ signals. Most of them exhibited a lymphoepithelioma
      like morphology. These results show that nested PCR is a sensitive method for
      screening the EBV genome in thymic epithelial tumours. In situ PCR ISH is
      reliable for localization of the virus, in addition to EBER-1 RNA ISH. Thymomas
      are not related to EBV, even in this endemic area. Thymic carcinomas, especially
      the lymphoepithelioma-like thymic carcinomas, are more often associated with the
      virus.

PMID- 12210091
TI  - Cathepsin K expression in epithelioid and multinucleated giant cells.

PMID- 12210094
TI  - Short window of opportunity for calpain induced growth cone formation after
      axotomy of Aplysia neurons.
AB  - Our laboratory has established that local activation of calpain by a transient
      elevation of the free intracellular calcium concentration is crucial for the
      induction of growth cone (GC) formation in cultured Aplysia neurons. The
      mechanisms and stages in which calpain is involved in the formation of a GC are
      not known. We began to study these questions by determining the nature of
      calpain's action and the stages in which calpain activity affects the cascade of
      events that leads to the formation of the GC and its extension. We report that
      the calpain-dependent transformation of an axonal segment into a GC occurs within
      a narrow window of opportunity that lasts approximately 5 min. If calpain is
      inhibited during this window of opportunity, GC formation does not occur.
      Inhibition of calpain after the window of opportunity slows down the rate of
      lamellipodial extension but doesn't arrest it. The proteolysis of spectrin, a
      calpain substrate and a major component of the membrane skeleton, occurs within
      this window of opportunity, in agreement with the hypothesis that spectrin
      proteolysis is an early step in the formation of the GC. If the onset of
      proteolysis is deferred, spectrin remains unchanged and GC formation is
      compromised. We suggest that calpain participates in two different processes: it
      is critical for the triggering of GC formation and plays a modulatory role during
      the extension of the GC's lamellipodia.

PMID- 12210095
TI  - Changing patterns of ganglion cell coupling and connexin expression during chick
      retinal development.
AB  - We have used dye injection and immunolabeling to investigate the relationship
      between connexin (Cx) expression and dye coupling between ganglion cells (GCs)
      and other cells of the embryonic chick retina between embryonic days 5 and 14 (E5
      14). At E5, GCs were usually coupled, via soma-somatic or dendro-somatic
      contacts, to only one or two other cells. Coupling increased with time until E11
      when GCs were often coupled to more than a dozen other cells with somata in the
      ganglion cell layer (GCL) or inner nuclear layer (INL). These coupled clusters
      occupied large areas of the retina and coupling was via dendro-dendritic
      contacts. By E14, after the onset of synaptogenesis and at a time of marked cell
      death, dye coupling was markedly decreased with GCs coupled to three or four
      partners. At this time, coupling was usually to cells of the same morphology,
      whereas earlier coupling was heterogeneous. Between E5 and E11, GCs were
      sometimes coupled to cells of neuroepithelial morphology that spanned the
      thickness of the retina. The expression of Cx 26, 32, and 43 differed and their
      distribution changed during the period studied, showing correlation with events
      such as proliferation, migration, and synaptogenesis. These results suggest
      specific roles for gap junctions and Cx's during retinal development.

PMID- 12210096
TI  - Female canaries that respond and discriminate more between male songs of
      different quality have a larger song control nucleus (HVC) in the brain.
AB  - In male songbirds the song control pathway in the forebrain is responsible for
      song production and learning. In most species, females do not sing and have
      smaller nuclei in the song control pathway. Although the function of the pathway
      in females is assumed to be associated with the perception of male song, there is
      little direct evidence to support this view. In this study on female canaries, we
      investigate the role of two key nuclei in the song control pathway (HVC and lMAN)
      in relation to playback of male song. Male canaries produce elaborate songs that
      function to attract and stimulate females. The songs are constructed from smaller
      units called syllables, and special syllables with a more complex structure (sexy
      syllables) are known to induce females to perform copulation solicitation
      displays (CSD) as an invitation to mate. By using computer-edited experimental
      songs, we first show that females discriminate between songs by producing
      significantly more CSD to those containing sexy syllables. We then sectioned the
      brains and used in situ hybridization to reveal song nuclei containing androgen
      receptors. We report positive correlations between the size of HVC and both total
      CSD response and the amount of discrimination between sexy and nonsexy songs. We
      found no such relationships between these measures and the size of lMAN. These
      results provide some evidence to support the view that, in female canaries HVC is
      involved in female perception and discrimination of male song. The results also
      have implications for the evolution of complex male songs by sexual selection and
      female choice.

PMID- 12210097
TI  - Mushroom bodies are not required for courtship behavior by normal and sexually
      mosaic Drosophila.
AB  - To elucidate the effect of feminization of male Drosophila brain cells on
      courtship control, we performed a large scale screening of expression drivers
      that can suppress male-specific behavior with transformer gene expression. Two
      drivers caused essentially total courtship suppression. The expression pattern of
      these drivers did not show any correlation with the mushroom bodies or the
      antennal lobes, the regions that have been suggested to play important roles in
      courtship. Ablation of mushroom bodies using hydroxyurea treatment did not affect
      this courtship suppression. The ablation did not change either wild-type
      heterosexual behavior or bisexual behavior caused by transformer expression
      driven by the same drivers used in the previous studies to suggest the
      involvement of the mushroom bodies in courtship. Our results show that
      feminization of different nonoverlapping cells in other parts of the
      protocerebrum was sufficient to cause the same bisexual or suppressed-courtship
      phenotype. Thus, contrary to previous assumptions, the mushroom bodies are not
      required for the control of courtship. Present evidence supports its mediation by
      other distributed protocerebral regions.

PMID- 12210098
TI  - Ovarian hormones after postnatal day 20 reduce neuron number in the rat primary
      visual cortex.
AB  - Previous work from our lab has documented a sex difference in neuron number in
      the binocular region of the adult rat primary visual cortex (Oc1B), with males
      having 19% more neurons than females. In the present study, the role of
      developmental steroid hormones in the formation of this difference was explored.
      Male and female rats underwent neonatal hormone manipulation (female +
      testosterone or dihydrotestosterone; male + flutamide) followed by gonadectomy on
      postnatal day 20. Animals that did not undergo hormone manipulation were either
      gonadectomized or sham operated at day 20. Neuron number was quantified in the
      monocular (Oc1M) and binocular (Oc1B) subfields of the adult rat primary visual
      cortex using the optical disector technique. As adults, day 20 gonadectomized
      females, as well as females + testosterone and females + dihydrotestosterone, had
      significantly more neurons than intact females. There was no difference in neuron
      number between postnatal day 20 gonadectomized males, males + flutamide, and
      intact males. Also, intact males had significantly more neurons than intact
      females in both in Oc1M and Oc1B. It appears that ovarian steroids after day 20
      are the primary cause of the lower number of neurons in the primary visual cortex
      of the female rat.

PMID- 12210099
TI  - Regeneration of retinal axons in the lizard Gallotia galloti is not linked to
      generation of new retinal ganglion cells.
AB  - Using anterograde tracing with HRP and antibodies (ABs) against neurofilaments,
      we show that regrowth of retinal ganglion cell (RGC) axons in the lizard Gallotia
      galloti commences only 2 months after optic nerve transection (ONS) and continues
      over at least 9 months. This is unusually long when compared to RGC axon
      regeneration in fish or amphibians. Following ONS, lizard RGCs up-regulate the
      immediate early gene C-JUN for 9 months or longer, indicating their reactive
      state. In keeping with the in vivo data, axon outgrowth from lizard retinal
      explants is increased above control levels from 6 weeks, reaches its maximum as
      late as 3 months, and remains elevated for at least 1 year after ONS. By means of
      BrdU incorporation assays and antiproliferating cell nuclear antigen
      immunohistochemistry, we show that the late axon outgrowth is not derived from
      new RGCs that might have arisen in reaction to ONS: no labeled cells were
      detected in lizard retinas at 0.5, 1, 1.5, 3, 6, and 12 months after ONS.
      Conversely, numbers of RGCs undergoing apoptosis were too low to be detectable in
      TUNEL assays at any time after ONS. These results demonstrate that retinal axon
      regeneration in G. galloti is due to axon regrowth from the resident population
      of RGCs, which remain in a reactive state over an extended time interval.
      Neurogenesis does not appear to be involved in RGC axon regrowth in G. galloti.

PMID- 12210100
TI  - Successive episodes of synapses production in the developing rat nucleus tractus
      solitarii.
AB  - In the rat nucleus tractus solitarii (NTS), synaptogenesis is thought to occur
      both pre- and postnatally. The present study was performed to precisely define
      the timetable of synapse formation in the NTS after birth. Changes in synapse
      morphology and densities were analyzed between postnatal day 3 (P3) and P28 using
      electron microscopy and ethanol phosphotungstic acid (E-PTA) staining. The
      proportion of morphologically immature synapses was high at P3 (38%) and P14
      (30%) and low (8-14%) at the other ages investigated (P7, P21, and P28). Synaptic
      density significantly increased between P7 and P14 (60%) and between P21 and P28
      (54%), but did not significantly change between P3 and P7 and between P14 and
      P21. Mean synaptic diameter also increased over the first postnatal month.
      Significant increases in synaptic size occurred between P3 and P7 (28%) and
      between P14 and P21 (15%). The present data indicate that, in the NTS,
      synaptogenesis occurs over a protracted period of time and involves distinct
      successive episodes of synapse production.

PMID- 12210101
TI  - Regulation of c-Ret, GFRalpha1, and GFRalpha2 in the substantia nigra pars
      compacta in a rat model of Parkinson's disease.
AB  - Glial cell line-derived neurotrophic factor (GDNF) family members have been
      proposed as candidates for the treatment of Parkinson's disease because they
      protect nigral dopaminergic neurons against various types of insult. However, the
      efficiency of these factors depends on the availability of their receptors after
      damage. We evaluated the changes in the expression of c-Ret, GFRalpha1, and
      GFRalpha2 in the substantia nigra pars compacta in a rat model of Parkinson's
      disease by in situ hybridization. Intrastriatal injection of 6-hydroxydopamine (6
      OHDA) transiently increased c-Ret and GFRalpha1 mRNA levels in the substantia
      nigra pars compacta at 1 day postlesion. At later time points, 3 and 6 days, the
      expression of c-Ret and GFRalpha1 was downregulated. GFRalpha2 expression was
      differentially regulated, as it decreased only 6 days after 6-OHDA injection.
      Triple-labeling studies, using in situ hybridization for the GDNF family
      receptors and immunohistochemistry for neuronal or glial cell markers, showed
      that changes in the expression of c-Ret, GFRalpha1, and GFRalpha2 in the
      substantia nigra pars compacta were localized to neurons. In conclusion, our
      results show that nigral neurons differentially regulate the expression of GDNF
      family receptors as a transient and compensatory response to 6-OHDA lesion.

PMID- 12210103
TI  - Development of the specialized AMPA receptors of auditory neurons.
AB  - At maturity, the AMPA receptors of auditory neurons exhibit very rapid
      desensitization kinetics and high permeability to calcium, reflecting the
      predominance of GluR3 flop and GluR4 flop subunits and the paucity of GluR2. We
      used mRNA analysis and immunoblotting to contrast the development of AMPA
      receptor structure in the chick cochlear nucleus [nucleus magnocellularis (NM)]
      with that of the slowly desensitizing and calcium-impermeable AMPA receptors of
      brainstem motor neurons in the nucleus of the glossopharyngeal/vagal nerves. The
      relative abundance of transcripts for GluRs 1-4 changes substantially in auditory
      (but not motor) neurons after embryonic day (E)10, with large decreases in GluR2
      and increases in GluR3 and GluR4. Relative to the motor neurons, NM neurons show
      a higher abundance of flop isoforms of GluRs 2-4 at E10, suggesting that auditory
      neurons are already biased toward expression of flop isoforms before the onset of
      synaptic function at E11. Immunoreactivities in NM show very distinct
      developmental patterns from E13 onward: GluR2 declines by >90%, GluR3 increases
      threefold, and GluR4 remains relatively constant. Our results show that there are
      a series of critical points during normal development, most occurring after the
      onset of function, when rapid changes in receptor structure (occurring via both
      transcriptional and post-transcriptional control mechanisms) produce the
      specialized AMPA receptor functions that enable auditory neurons to accurately
      encode acoustic information.

PMID- 12210102
TI  - Myosin light chain phosphorylation and growth cone motility.
AB  - According to the treadmill hypothesis, the rate of growth cone advance depends
      upon the difference between the rates of protrusion (powered by actin
      polymerization at the leading edge) and retrograde F-actin flow, powered by
      activated myosin. Myosin II, a strong candidate for powering the retrograde flow,
      is activated by myosin light chain (MLC) phosphorylation. Earlier results showing
      that pharmacological inhibition of myosin light chain kinase (MLCK) causes growth
      cone collapse with loss of F-actin-based structures are seemingly inconsistent
      with the treadmill hypothesis, which predicts faster growth cone advance. These
      experiments re-examine this issue using an inhibitory pseudosubstrate peptide
      taken from the MLCK sequence and coupled to the fatty acid stearate to allow it
      to cross the membrane. At 5-25 microM, the peptide completely collapsed growth
      cones from goldfish retina with a progressive loss of lamellipodia and then
      filopodia, as seen with pharmacological inhibitors, but fully reversible. Lower
      concentrations (2.5 microM) both simplified the growth cone (fewer filopodia) and
      caused faster advance, doubling growth rates for many axons (51-102 microm/h; p
      <.025). Rhodamine-phalloidin staining showed reduced F-actin content in the
      faster growing growth cones, and marked reductions in collapsed ones. At higher
      concentrations, there was a transient advance of individual filopodia before
      collapse (also seen with the general myosin inhibitor, butanedione monoxime,
      which did not accelerate growth). The rho/rho kinase pathway modulates MLC
      dephosphorylation by myosin-bound protein phosphatase 1 (MPP1), and manipulations
      of MPP1 also altered motility. Lysophosphatidic acid (10 microM), which causes
      inhibition of MPP1 to accumulate activated myosin II, caused a contracted
      collapse (vs. that due to loss of F-actin) but was ineffective after treatment
      with low doses of peptide, demonstrating that the peptide acts via MLC
      phosphorylation. Inhibiting rho kinase with Y27632 (100 microM) to disinhibit the
      phosphatase increased the growth rate like the MLCK peptide, as expected. These
      results suggest that: varying the level of MLCK activity inversely affects the
      rate of growth cone advance, consistent with the treadmill hypothesis and myosin
      II powering of retrograde F-actin flow; MLCK activity in growth cones, as in
      fibroblasts, contributes strongly to controlling the amount of F-actin; and the
      phosphatase is already highly active in these cultures, because rho kinase
      inhibition produces much smaller effects on growth than does MLCK inhibition.

PMID- 12210104
TI  - Evidence for species differences in the pattern of androgen receptor distribution
      in relation to species differences in an androgen-dependent behavior.
AB  - Chickens (Gallus gallus domesticus) and Japanese quail (Coturnix japonica), two
      closely related gallinaceous bird species, exhibit a form of vocalization-crowing
      which differs between the species in two components: its temporal acoustic
      pattern and its accompanying postural motor pattern. Previous work utilizing the
      quail-chick chimera technique demonstrated that the species-specific
      characteristics of the two crow components are determined by distinct brain
      structures: the midbrain confers the acoustic pattern, and the caudal hindbrain
      confers the postural pattern. Crowing is induced by androgens, acting directly on
      androgen receptors. As a strategy for identifying candidate neurons in the
      midbrain and caudal hindbrain that could be involved in crow production, we
      performed immunocytochemistry for androgen receptors in these brain regions in
      both species. We also investigated midbrain-to-hindbrain vocal-motor projections.
      In the midbrain, both species showed prominent androgen receptor immunoreactivity
      in the nucleus intercollicularis, as had been reported in previous studies. In
      the caudal hindbrain, we discovered characteristic species differences in the
      pattern of androgen receptor distribution. Chickens, but not quail, showed strong
      immunoreactivity in the tracheosyringeal division of the hypoglossal nucleus,
      whereas quail, but not chickens, possessed strong immunoreactivity in a region of
      the ventrolateral medulla. Some of these differences in hindbrain androgen
      receptor distribution may be related to the species differences in the postural
      component of crowing behavior. The results of the present study imply that the
      spatial distribution of receptor proteins can vary even between closely related
      species. Such variation in receptor distribution could underlie the evolution of
      species differences in behavior.

PMID- 12210105
TI  - Early and transient ontogenetic expression of the cocaine- and amphetamine
      regulated transcript peptide in the rat mesencephalon: correlation with tyrosine
      hydroxylase expression.
AB  - The ontogeny of cocaine- and amphetamine-regulated transcript (CART) expression
      has been analyzed by immunohistochemistry in the mesencephalon of the rat central
      nervous system, and compared to the pattern of tyrosine hydroxylase- (TH-)
      expression. CART-producing neurons were first detected on the embryonic day 11
      (E11) in the ventral mesencephalic vesicle. These neurons are among the first
      cells of the mantle layer to differentiate. From E13, a complementary pattern of
      distribution was observed, dividing the mantle layer into an external TH zone and
      an internal CART zone. Many TH-positive neurons were found to migrate from the
      neuroepithelium through the area containing the CART-immunoreactive neurons to
      settle more laterally. These TH cells exhibited prominent leading and trailing
      dendrites in the immediate vicinity of CART perikarya. On E16, the number of CART
      neurons appeared to diminish, and they were confined near the ventricle and
      around the fasciculus retroflexus. On E18 and E20, only the Edinger-Westphal
      nucleus exhibited a strong CART staining as described in the adult brain. Thus,
      the very early detection of CART during prenatal ontogeny led us to speculate
      that this peptide might have a role in the development of specific regions of the
      rat brain. In particular, our observations suggest that CART-expressing neurons
      might help the migration of the dopaminergic neurons of the substantia nigra.

PMID- 12210106
TI  - Presynaptic adenosine A1 receptors regulate retinohypothalamic neurotransmission
      in the hamster suprachiasmatic nucleus.
AB  - Adenosine has been implicated as a modulator of retinohypothalamic
      neurotransmission in the suprachiasmatic nucleus (SCN), the seat of the light
      entrainable circadian clock in mammals. Intracellular recordings were made from
      SCN neurons in slices of hamster hypothalamus using the in situ whole-cell patch
      clamp method. A monosynaptic, glutamatergic, excitatory postsynaptic current
      (EPSC) was evoked by stimulation of the optic nerve. The EPSC was blocked by bath
      application of the adenosine A(1) receptor agonist cyclohexyladenosine (CHA) in a
      dose-dependent manner with a half-maximal concentration of 1.7 microM. The block
      of EPSC amplitude by CHA was antagonized by concurrent application of the
      adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX).
      The adenosine A(2A) receptor agonist CGS21680 was ineffective in attenuating the
      EPSC at concentrations up to 50 microM. Trains of four consecutive stimuli at 25
      ms intervals usually depressed the EPSC amplitude. However, after application of
      CHA, consecutive responses displayed facilitation of EPSC amplitude. The
      induction of facilitation by CHA suggested a presynaptic mechanism of action.
      After application of CHA, the frequency of spontaneous EPSCs declined
      substantially, while their amplitude distribution was unchanged or slightly
      reduced, again suggesting a mainly presynaptic site of action for CHA.
      Application of glutamate by brief pressure ejection evoked a long-lasting inward
      current that was unaffected by CHA at concentrations sufficient to reduce the
      evoked EPSC amplitude substantially (1 to 5 microM), suggesting that postsynaptic
      glutamate receptor-gated currents were unaffected by the drug. Taken together,
      these observations indicate that CHA inhibits optic nerve-evoked EPSCs in SCN
      neurons by a predominantly presynaptic mechanism.

PMID- 12210107
TI  - Pre- and postsynaptic mechanisms in Hebbian activity-dependent synapse
      modification.
AB  - We have used a three compartment tissue culture system that involved two separate
      populations of cholinergic neurons in the side compartments that converged on a
      common target population of myotubes in the center compartment. Activation of the
      axons from one population of neurons produced selective down-regulation of the
      synaptic inputs from the other neuronal population (when the two inputs
      innervated the same myotubes). The decrease in heterosynaptic inputs was mediated
      by protein kinase C (PKC). An activity-dependent action of protein kinase A (PKA)
      was associated with the stimulated input and this served to selectively stabilize
      this input. These changes associated with PKA and PKC activation were mediated by
      alterations in the number of acetylcholine receptors at the neuromuscular
      junction. These results suggest that neuromuscular electrical activity produces
      postsynaptic activation of both PKA and PKC, with the latter producing
      generalized synapse weakening and the former a selective synapse stabilization.
      Treatment of the neuronal cell body and axon to increase PKC activity by putting
      phorbal ester (PMA) in the side chamber did not affect synaptic transmission
      (with or without stimulation). By contrast, PKA blockade in the side compartment
      did produce an activity-dependent decrease in synaptic efficacy, which was due to
      a decrease in quantal release of neurotransmitter. Thus, when the synapse is
      activated, it appears that presynaptic PKA action is necessary to maintain
      transmitter output.

PMID- 12210108
TI  - Initial stages of radial glia astrocytic transformation in the early postnatal
      anterior subventricular zone.
AB  - In the early postnatal subventricular zone (SVZ), two seemingly unrelated events
      occur simultaneously: a massive tangential migration of neuroblasts towards the
      olfactory bulb, known as the rostral migratory stream (RMS), and the outward
      movement of radial glia (RG) undergoing astrocytic transformation. Because of the
      orthogonal arrangement between these two sets of cells, little, if any, relevance
      has been ascribed for their possible interactions. By depositing DiI at the pial
      surface we have studied RG transformation within the SVZ/RMS, from birth up to
      the end of the first postnatal week. While still within the SVZ/RMS, RG
      morphology changed from simple bipolar to highly complex branched profiles,
      attaining their highest degree of complexity at the interface of the SVZ with the
      overlying white matter. At this interface cell bodies of radial glia accumulate
      and their processes run tangentially, surrounding the SVZ/RMS. Processes of RG
      surrounding the SVZ/RMS could also be observed by immunostaining for vimentin,
      GFAP, and nestin. In contrast, in the white matter all DiI-labeled RG presented a
      simple bipolar profile. These results indicate that the outward radial migration
      of the transforming RG does not occur uniformly. Instead, the different
      morphologies and cell densities that RG assume when they cross the SVZ/RMS and
      overlying white matter imply different migratory behaviors. Finally, our data
      suggest that RG provide a cellular scaffold to the early postnatal SVZ/RMS, much
      in the same way as astrocytes in the adult RMS.

PMID- 12210109
TI  - Evolution of median fin modules in the axial skeleton of fishes.
AB  - Detailed examples of how hierarchical assemblages of modules change over time are
      few. We found broadly conserved phylogenetic patterns in the directions of
      development within the median fins of fishes. From these, we identify four
      modules involved in their positioning and patterning. The evolutionary sequence
      of their hierarchical assembly and secondary dissociation is described. The
      changes in these modules during the evolution of fishes appear to be produced
      through dissociation, duplication and divergence, and co-option. Although the
      relationship between identified median fin modules and underlying mechanisms is
      unclear, Hox addresses may be correlated. Comparing homologous gene expression
      and function in various fishes may test these predictions.The earliest
      actinopterygians likely had dorsal and anal fins that were symmetrically
      positioned via a positioning module. The common patterning (differentiation) of
      skeletal elements within the dorsal and anal fins may have been set into motion
      by linkage to this positioning module. Frequent evolutionary changes in dorsal
      and anal fin position indicate a high level of dissociability of the positioning
      module from the patterning module. In contrast, the patterning of the dorsal and
      anal fins remains linked: In nearly all fishes, the endo- and exoskeletal
      elements of the two fins co-differentiate. In all fishes, the exoskeletal fin
      rays differentiate in the same directions as the endoskeletal supports,
      indicating complete developmental integration. In acanthopterygians, a new first
      dorsal fin module evolved via duplication and divergence. The median fins provide
      an example of how basic modularity is maintained over 400 million years of
      evolution.

PMID- 12210110
TI  - Conservation and variation in enamel protein distribution during vertebrate tooth
      development.
AB  - Vertebrate enamel formation is a unique synthesis of the function of highly
      specialized enamel proteins and their effect on the growth and organization of
      apatite crystals. Among tetrapods, the physical structure of enamel is highly
      conserved, while there is a greater variety of enameloid tooth coverings in fish.
      In the present study, we postulated that in enamel microstructures of similar
      organization, the principle components of the enamel protein matrix would have to
      be highly conserved. In order to identify the enamel proteins that might be most
      highly conserved and thus potentially most essential to the process of mammalian
      enamel formation, we used immunoscreening with enamel protein antibodies as a
      means to assay for degrees of homology to mammalian enamel proteins. Enamel
      preparations from mouse, gecko, frog, lungfish, and shark were screened with
      mammalian enamel protein antibodies, including amelogenin, enamelin, tuftelin,
      MMP20, and EMSP1. Our results demonstrated that amelogenin was the most highly
      conserved enamel protein associated with the enamel organ, enamelin featured a
      distinct presence in shark enameloid but was also present in the enamel organ of
      other species, while the other enamel proteins, tuftelin, MMP20, and EMSP1, were
      detected in both in the enamel organ and in other tissues of all species
      investigated. We thus conclude that the investigated enamel proteins, amelogenin,
      enamelin, tuftelin, MMP20, and EMSP1, were highly conserved in a variety of
      vertebrate species. We speculate that there might be a unique correlation between
      amelogenin-rich tetrapod and lungfish enamel with long and parallel crystals and
      enamelin-rich basal vertebrate enameloid with diverse patterns of crystal
      organization.

PMID- 12210111
TI  - Characterization of Hox genes in the bichir, Polypterus palmas.
AB  - It has been suggested that the increase in the number of Hox genes may have been
      one of the key events in vertebrate evolution. Invertebrates have one Hox
      cluster, while mammals have four. Interestingly, the number of Hox gene clusters
      is greater in the teleost fishes, zebrafish and medaka, than in mouse and human.
      The greater number of Hox clusters in the teleosts suggests that Hox gene
      duplication events have occurred during the radiation of ray-finned fishes. The
      question is when the Hox gene duplication event(s) that lead to seven Hox
      clusters in the teleosts actually occurred. We have addressed this question by
      studying the Hox genes in the bichir, Polypterus palmas. A preliminary PCR
      estimation of the number of Hox genes suggests that Polypterus has five different
      Hox9 cognate group genes, which may be an indication of more than four Hox
      clusters in the bichir.

PMID- 12210112
TI  - Evolution of developmental functions by the Eomesodermin, T-brain-1, Tbx21
      subfamily of T-box genes: insights from amphioxus.
AB  - We have identified an amphioxus T-box gene that is orthologous to the
      Eomesodermin, T-brain-1, and Tbx21 genes of vertebrates, and we have
      characterized its expression pattern during embryonic and larval development.
      AmphiEomes/Tbr1/Tbx21 is maternally expressed in oocytes and cleavage stage
      embryos. After the onset of zygotic transcription at the blastula stage, it is
      expressed in invaginating mesendoderm cells during gastrulation, but it is
      downregulated in presumptive ectoderm and neurectoderm. Expression is seen in
      both axial and paraxial mesendoderm in neurulae and early larvae, but it is not
      detected in differentiated endoderm, somites, or notochord. Expression persists
      in mesendoderm cells of the tail bud in early larvae, but it disappears between 1
      to 1.5 days post fertilization. Unlike orthologous genes in basal deuterostomes
      or vertebrates, no anterior neural expression domain is detected at any stage of
      development. Integrating phylogenetic and developmental data, we have
      reconstructed the evolutionary history of the Eomesodermin/Tbr1/Tbx21 subfamily
      of T-box genes from a single ancestral locus that originated very early in
      metazoan evolution, before the evolution of triploblasts from their diploblast
      ancestor.

PMID- 12210113
TI  - Aperture pattern ontogeny in angiosperms.
AB  - Pollen grains display a wide range of variation in aperture number and
      arrangement (pattern) in angiosperms. Apertures are well-defined areas of the
      pollen wall surface that permit pollen tube germination. For low aperture
      numbers, aperture patterns are characteristic of the major taxonomic divisions of
      angiosperms. This paper presents a developmental model that explains most of the
      aperture patterns that are recorded in angiosperms. It is based on the analysis
      of the different events that occur during meiosis and lead to microspore
      differentiation. It demonstrates that variation occurring during meiosis in
      angiosperms is sufficient to produce the core morphological set of the most
      commonly observed pollen morphologies.

PMID- 12210114
TI  - Amphi-Eomes/Tbr1: an amphioxus cognate of vertebrate Eomesodermin and T-Brain1
      genes whose expression reveals evolutionarily distinct domain in amphioxus
      development.
AB  - A cDNA for a novel T-box containing gene was isolated from the amphioxus
      Branchiostoma belcheri. A molecular phylogenetic tree constructed from the
      deduced amino acid sequence of the isolated cDNA indicates that this gene belongs
      to the T-Brain subfamily. In situ hybridization reveals that the expression is
      first detected in the invaginating archenteron at the early gastrula stage and
      this expression is down-regulated at the neurula stage. In early larvae, the
      expression appears again and transcripts are detected exclusively in the pre-oral
      pit (wheel organ-Hatschek's pit of the adult). In contrast to the vertebrate
      counterparts, no transcripts are detected in the brain vesicle or nerve cord
      throughout the development. These results are interpreted to mean that a role of
      T-Brain products in vertebrate forebrain development was acquired after the
      amphioxus was split from the lineage leading to the vertebrates. On the other
      hand, comparison of the tissue-specific expression domain of T-Brain genes and
      other genes between amphioxus and vertebrates revealed that the pre-oral pit of
      amphioxus has several molecular features which are comparable to those of the
      vertebrate olfactory and hypophyseal placode.

PMID- 12210115
TI  - Pentadactyl ground state of the avian wing.
AB  - The issue of the homology of bird fingers with those of pentadactyl amniotes has
      been a topic of contention for nearly 200 years. Data from the fossil record and
      phylogenetic systematics ascribe bird digit homologies to digits I, II, and III
      of pentadactyl amniotes while embryological evidence supports digital homologies
      of II, III, and IV. Using a molecular marker specific for condensation competent
      mesenchymal cells, we describe a pentadactyl arrangement of prechondrogenic
      digital anlagen in the wings of stage 29 chick embryos. Only the middle three
      anlagen develop into mature fingers. This pattern supports the hypothesis that
      bird fingers develop from digital anlagen II, III, and IV of pentadactylous
      amniotes. In addition, this result rejects a model assuming a shift in the
      primary axis in bird digit development and shows that a prechondrogenic digital
      anlage has been maintained in the bird lineage for at least 220 million years
      since the last known pentadactylous ancestor of the lineage. Such a vestige
      suggests that strong constraints are maintaining a pentadactyl ground state in
      amniotes.

PMID- 12210116
TI  - Pentadactyl pattern of the avian wing autopodium and pyramid reduction
      hypothesis.
AB  - We report herein that a pentadactyl developmental pattern is evident in early
      wing morphogenesis of Gallus (chicken) and Struthio (ostrich). Five avascular
      zones (spatially predestined locations of contiguous metacarpal and phalangeal
      aggregation) and four interdigital vascular spaces are established by the
      regression patterns of autopodial vasculature. Transient vestiges of the first
      and fifth metacarpals are confirmed histologically and histochemically. They lie
      within the preaxial-most and postaxial-most avascular zones, respectively. These
      observations reveal conservative patterning of the avian hand and corroborate a
      II-III-IV metacarpal interpretation, argue for II-III-IV identity of ossified
      digits in birds, and favour a simple reduction rather than a homeotic shift in
      terms of the phenotype expressed by Hox genes in the phylogeny of the avian
      manus. We suggest that gradual, bilateral reduction of phalanges and metacarpals,
      via apoptosis mediated by BMP, occurred during the evolution of birds (Pyramid
      Reduction Hypothesis). This is congruent with the establishment of a central wing
      axis that became co-opted for coordinated movements. On the basis of evidence
      presented here, the direct avian ancestor is predicted to have been five-fingered
      with dominant digits (+ metacarpals) as follow: II, III, IV.

PMID- 12210117
TI  - Shh-Bmp2 signaling module and the evolutionary origin and diversification of
      feathers.
AB  - To examine the role of development in the origin of evolutionary novelties, we
      investigated the developmental mechanisms involved in the formation of a complex
      morphological novelty-branched feathers. We demonstrate that the anterior
      posterior expression polarity of Sonic hedgehog (Shh) and Bone morphogenetic
      protein 2 (Bmp2) in the primordia of feathers, avian scales, and alligator scales
      is conserved and phylogenetically primitive to archosaurian integumentary
      appendages. In feather development, derived patterns of Shh-Bmp2 signaling are
      associated with the development of evolutionarily novel feather structures.
      Longitudinal Shh-Bmp2 expression domains in the marginal plate epithelium between
      barb ridges provide a prepattern of the barbs and rachis. Thus, control of Shh
      Bmp2 signaling is a fundamental component of the mechanism determining feather
      form (i.e., plumulaceous vs. pennaceous structure). We show that Shh signaling is
      necessary for the formation and proper differentiation of a barb ridge and that
      it is mediated by Bmp signaling. BMP signaling is necessary and sufficient to
      negatively regulate Shh expression within forming feather germs and this
      epistatic relationship is conserved in scale morphogenesis. Ectopic SHH and BMP2
      signaling leads to opposing effects on proliferation and differentiation within
      the feather germ, suggesting that the integrative signaling between Shh and Bmp2
      is a means to regulate controlled growth and differentiation of forming skin
      appendages. We conclude that Shh and Bmp signaling is necessary for the formation
      of barb ridges in feathers and that Shh and Bmp2 signaling constitutes a
      functionally conserved developmental signaling module in archosaur epidermal
      appendage development. We propose a model in which branched feather form evolved
      by repeated, evolutionary re-utilization of a Shh-Bmp2 signaling module in new
      developmental contexts. Feather animation Quicktime movies can be viewed at
      http://fallon.anatomy.wisc.edu/feather.html.

PMID- 12210118
TI  - Differential regulation of spontaneous and heat-induced HSP 70 expression in
      developing zebrafish (Danio rerio).
AB  - A spontaneous high expression of heat shock protein 70 (HSP 70) was found to
      arise in zebrafish (Danio rerio) at the larval stage (84 hr after fertilization).
      The level of HSP 70 in 84-hr-old larvae was estimated to be six- to eightfold
      that of 12-hr-old embryos. As heat-induced HSP 70 synthesis in many eukaryotic
      organisms is known to be mediated by a transcriptional-dependent pathway
      activated by heat shock factor 1 (HSF-1), we then examined if the spontaneous and
      heat-induced HSP 70 synthesis in zebrafish were controlled by the same mechanism.
      Although the transient increase of a 62-kDa HSF-1-like polypeptide in 72- to 96
      hr-old larvae seemed to correlate with the onset of the spontaneous HSP 70
      production, an anti-HSF-1 antibody cocktail supershifted the heat shock element
      (HSE) binding complex induced by stressed but not by unstressed zebrafish
      extracts. Northern blot and quantitative RT-PCR analysis demonstrated the
      predominant presence of the cognate form of hsp 70 mRNA (hsc 70 mRNA) in
      developing zebrafish. The extent of heat-induced HSP 70 production in 84-hr-old
      larvae matched well with a dramatic increase in hsp 70 mRNA accumulation, while
      no apparent increase in total hsp 70 mRNA could be detected in 72- to 84-hr-old
      unstressed larvae by northern blot analysis. The stable expression of hsc 70 mRNA
      specific to beta-actin mRNA in normal zebrafish was confirmed by RT-PCR analysis.
      Hence, the spontaneous high expression of HSP 70 in zebrafish is believed to be
      controlled by a mechanism different from the HSF-1-dependent transcriptional
      activation of hsp 70 under heat stress. J. Exp. Zool. 293:349-359, 2002.

PMID- 12210119
TI  - Mechanical performance and glycolytic requirement in trout ventricular muscle.
AB  - The glycolytic pathway seems to be coupled to the aerobic performance in
      mammalian cardiac muscle. Because many conditions are different in ectotherms,
      its influence on twitch force and resting force was recorded at 15 degrees C in
      isometric ventricular preparations from rainbow trout. To reduce glycolytic
      activity, preparations were exposed to 0.4 mmol l(-1) iodoacetate for 35 min or
      alternatively to 120 min anoxia in a glucose-free solution containing 10 &mgr;mol
      l(-1) adrenaline in an attempt to remove glycolytic substrates. The anoxic period
      was followed by recovery in an oxygenated solution containing aerobic substrates
      but no glucose. Control experiments indicated that this treatment, like
      iodoacetate, inhibits glycolysis, although glycogen was reduced by one half only.
      In fully oxygenated preparations with access to mitochondrial substrates, both
      attempts to reduce glycolytic activity tended to increase both resting force and
      the reductions in twitch force during high activity imposed by high stimulation
      rates and exposure to 10 &mgr;mol l(-1) adrenaline. Thus, the glycolytic pathway
      appears to be of specific importance under aerobic conditions also in the heart
      of ectotherms. J. Exp. Zool. 293:360-367, 2002.

PMID- 12210120
TI  - Molecular cloning and immunohistochemical localization of ubiquitin C-Terminal
      hydrolase expressed in testis of a teleost, the Nile Tilapia, Oreochromis
      niloticus.
AB  - We previously produced four monoclonal antibodies to testicular proteins of a
      teleost, the Nile tilapia. One of the monoclonal antibodies, TAT(Testicular
      Antigen of Tilapia)-10, recognizes a Mr=27,000 protein (27 kD protein), which is
      present in A and early B type spermatogonia, spermatids, and spermatozoa in
      testis. In order to clarify the function of this protein, molecular cloning was
      conducted. The cDNA for the 27 kD protein contains a complete open reading frame
      encoding 220 amino acid residues. The predicted amino acid sequence of the 27 kD
      protein was homologous to those of the ubiquitin carboxy-terminal hydrolases
      (UCH) reported in mammals. The measurement of the ubiquitin-releasing activity of
      the recombinant 27 kD protein revealed that the protein is the active form of
      UCH. Northern blot analysis showed that the UCH mRNA was expressed in ovary and
      brain in addition to the testis. Immunohistochemical study showed that, in brain,
      UCH was localized especially on the olfactory organ including the olfactory bulb
      and olfactory epithelium in olfactory rosetta, suggesting the involvement of the
      protein in chemoreceptive function. In the Tilapia ovary, UCH localized
      especially in pre-vitellogenic oocytes, suggesting that the enzyme activity could
      be important in oocyte growth. This is the first report for the cDNA cloning and
      cellular localization of UCH in fish. J. Exp. Zool. 293:368-383, 2002.

PMID- 12210121
TI  - Gallium nitrate: effects on cartilage during limb regeneration in the axolotl,
      Ambystoma mexicanum.
AB  - Gallium nitrate, a drug shown to have efficacy in Paget's disease of bone,
      hypercalcemia of malignancy, and a variety of experimental autoimmune diseases,
      also inhibits the growth of some types of cancer. We examined dose and timing of
      administration of gallium nitrate on limb regeneration in the Mexican axolotl,
      Ambystoma mexicanum. Administered by intraperitoneal injection, gallium nitrate
      inhibited limb regeneration in a dose-dependent manner. Gallium nitrate initially
      suppressed epithelial wound healing and subsequently distorted both anterior
      posterior and proximo-distal chondrogenic patterns. Gallium nitrate given at
      three days after amputation severely inhibited regeneration at high doses (6.25
      mg/axolotl) and altered the normal patterning of the regenerates at low doses
      (3.75 mg/axolotl). Administration of 6.25 mg of gallium nitrate at four or 14
      days prior to amputation also inhibited regeneration. In amputated limbs of
      gallium-treated axolotls, the chondrocytes were lost from inside the radius/ulna.
      Limbs that regenerated after gallium treatment was terminated showed blastema
      formation preferentially over the ulna. New cartilage of the regenerate often
      attached to the sides of the existing radius/ulna proximally into the stump and
      less so to the distal cut ends. J. Exp. Zool. 293:384-394, 2002.

PMID- 12210122
TI  - Distribution of GFAP immunoreactive structures in the rhombencephalon of the
      sterlet (Acipenser ruthenus) and its evolutionary implication.
AB  - Previous studies have revealed that although the brains of cypriniform teleosts
      (iberian barb, Barbus comiza; carp, Cyprinus carpio; goldfish, Carassius auratus)
      are rich in glial fibrillary acidic protein (GFAP), they have, however, areas
      devoid of GFAP immunoreactivity. The largest ones of these are in the
      rhombencephalon, e.g., the zones of the sensory and motor neurons in the vagal
      lobe. Our studies in amniotes suggested that the GFAP immunonegative areas could
      be characteristic of the more advanced brains (avian and mammalian), whereas no
      similar areas were found in reptiles. A similar tendency was found in the
      Chondrichthyes, i.e., GFAP immunonegative areas appeared as brain complexity
      progressed. The question arose whether the GFAP immunonegative brain areas in the
      Teleostei were also the result of such a tendency. Within the radiation of ray
      finned fishes (Actinopterygii), Chondrostei represent a less advanced level as
      compared to the Teleostei. Therefore, the distribution of GFAP immunoreactivity
      was investigated in the rhombencephalon of the sterlet (Acipenser ruthenus) as a
      representative of Chondrostei, and in the carp. Serial vibratome sections were
      processed according to the avidin-biotinylated horseradish peroxidase
      method.Several comparable GFAP immunoreactive structures were found in the two
      species: the dense periventricular ependymoglial plexus, the midsagittal glial
      septum, the small glial septa separating the nerve fiber bundles, and the wide
      glial endfeet lining the meningeal surface. In the vagal lobe in the zones
      adjacent to the meningeal and ventricular surfaces, the glial structures also
      proved to be similar. In contrast to the carp, however, no areas were found
      devoid of GFAP immunoreactivity in the sterlet.The results suggest that this
      trend of glial evolution, i.e., GFAP immunonegative areas appearing as brain
      complexity progressed, is a common feature shared by Actinopterygii, Amniota, and
      Chondrichthyes, despite their separate evolutionary histories. J. Exp. Zool.
      293:395-406, 2002.

PMID- 12210123
TI  - Effect of hypothyroidism induced by propylthiouracil on ovarian function and
      structure in offspring from treated mothers (Rats).
AB  - The aim of the present study was to investigate the effects of hypothyroidism
      induced during the pre- and postnatal periods of life on ovarian function and
      structure in offspring (pups) 120 days of age. Three groups were used. In the
      prenatal group, treatment was given from conception to parturition. In the
      postnatal group, treatment was given from parturition to 25 days postpartum.
      Hypothyroidism was induced by administration of 0.1% 6-n-propyl-2-thiouracil
      (PTU) in the drinking water of mothers. Body weights of the offspring were
      measured weekly. In each group, ten offspring were sacrificed at 120 days of age.
      Postnatal PTU treated pups showed delay in eye opening, teething, fur
      development, and weaning (35-37 days) compared to control animals (28-30 days).
      Body weight of offspring in the postnatal PTU treatment group was significantly
      decreased (P < 0.001), while the prenatal PTU treatment group showed a
      significant increase (P < 0.0001) compared to control animals. There was a
      significant (P < 0.05) reduction in paired ovarian weight of offspring in the
      postnatal PTU treatment group compared to control animals. Diameter of the
      ovaries was not affected by any treatment. Regarding the morphometery, only
      offspring in the prenatal PTU treatment group showed a significant (P < 0.001)
      increase in the diameter of graafian follicles. No significant difference was
      observed in morphometery of the granulosa layer, primary, and developing
      follicles of control and all treated groups. Number of primary, developing, and
      graafian follicles of all the treated groups was similar to that of the control
      group. The corpora lutea of the postnatal PTU treated group contained a
      population of large numbers of luteal cells compared to the control group. The
      prenatal PTU treated group did not exhibit a profound effect on ovarian
      morphology, histology, and morphometery. No difference was found in the serum
      estradiol concentration of control and PTU treated groups. J. Exp. Zool. 293:407
      413, 2002.

PMID- 12210124
TI  - Cuticle Ultrastructure Changes in the Crab Scylla serrata Over the Molt Cycle.
AB  - Morphological and chemical studies on the cuticle during the molt cycle of the
      crab Scylla serrata were performed in order to understand the layer formation.
      Cuticle ultrastructure was studied by scanning electron microscopy (SEM). Energy
      dispersive, X-ray diffraction, and X-ray fluorescence analysis were used for
      identification of the elements and phases in the inner surface of the cuticle. In
      the first stage (A) of cuticle formation, a thin pellicle organized as an
      irregular fragmented structure is built. It is composed mainly of alpha
      chitin/protein beta-keratin-like complexes where heterogeneous mineral nucleation
      occur. It is impregnated by ferric concretions, responsible for the brown colour
      of the carapace. At the beginning of the mineralization process, a spheroidal
      inorganic phase appears consisting of dicalcium phosphate dihydrate (DCPD)
      Ca/P=1.00, octacalcium phosphate (OCP) Ca/P=1.33 associated with hydromagnesite
      and bromapatite traces. During further cuticle development in the remaining A
      stage and in the beginning of the B stage, calcite and magnesian calcite are
      formed from the precursor calcium phosphate phase. The next development in the C
      stages is characterized by intense calcareous thickening consisting mainly of
      calcite and of magnesian calcite, which become the major mineral fraction of the
      cuticle. Organic-inorganic complex precipitations exhibit different aspects as
      spongiform, filamentary helicoidal, and concentric radial arrangements during C1,
      C2, and C3, respectively. During different stages of the cuticle formation in
      Scylla serrata, these mineral deposits may partially result from the balance
      among different organic contents, mainly between alpha-chitin and protein beta
      keratin-like compounds. On the other hand, the calcium crystallization on apatite
      and calcite polymorphic structures may be influenced by variations of physico
      chemical factors in the cuticle compartment. J. Exp. Zool. 293:414-426, 2002.

PMID- 12210125
TI  - Myocyte ploidy in heart chambers of birds with different locomotor activity.
AB  - The ploidy levels of atrio- and ventriculocytes were determined by means of
      cytofluorimetry in 31 species of birds. The obtained data were collated with
      postnatal growth rate, heart mass index, and relative masses of heart chambers.
      The difference between mean ploidy of cardiomyocytes in the left and right atrium
      is small (7.9+/-0.6%) and comparable to the difference in the masses of these
      chambers (10.5+/-0.8%). The difference between mean ploidy of atrio- and
      ventriculocytes is most pronounced for the left and right parts of heart (23.9+/
      1.4% and 24.0+/-1.3%, respectively) and corresponds to considerable differences
      in the average masses of atria and ventricles (4.5-fold and 2.1-fold,
      respectively). The mean cardiomyocyte ploidy levels in the left and right
      ventricles differ only slightly, as in the case of atria (by 8.1+/-0.5%), whereas
      the average mass of the left ventricle is greater by 237+/-16%. This discord can
      be explained by peculiarities of the growth, which is nonproportionally faster in
      the left ventricle during the last stage of proliferative heart growth as
      compared to other chambers. The cardiomyocyte ploidy is higher in birds with a
      relatively small heart and lower ability to flight. Birds with a high locomotor
      activity in the adult state have an athletic heart (mass index >1%); they are
      fast growing, altricial species with a low heart workload in the early postnatal
      ontogenesis. Birds with a low locomotor activity at the adult state are
      precocial; they grow slowly and have a high locomotor activity from the first
      minutes of life. Thus, notwithstanding the fact that a greater elevation of
      cardiomyocyte ploidy level is acquired under a higher functional load (ventricles
      vs. atria, left vs. right part of the heart), it is associated with a lower
      functional potential of the organ at the adult state. The level of somatic
      polyploidy can be considered an indicator of developmental tensions arising due
      to a high workload during the growth of a given organ and deficiency of resources
      invested into this growth. J. Exp. Zool. 293:427-441, 2002.

PMID- 12210126
TI  - Some observations on cortical inputs to the macaque monkey amygdala: an
      anterograde tracing study.
AB  - We have previously described the origins of neocortical inputs to the lateral
      nucleus of the macaque monkey amygdala based on retrograde tracing studies. Here
      we report results from studies that have attempted to confirm the projections
      from several candidate afferent regions using (3)H-amino acid autoradiography as
      an anterograde tracer. We have charted, based on the results of 33 separate
      injections, the topographic distribution of cortical projections throughout the
      amygdala. Areas TE and TEO of the inferotemporal cortex, portions of the superior
      temporal gyrus, and the granular region of the insula project primarily to the
      lateral nucleus, with little or no innervation of other amygdaloid nuclei. In
      contrast, orbitofrontal, medial prefrontal, and anterior cingulate regions
      project primarily to the basal and accessory basal nuclei and provide little
      innervation to the lateral nucleus. The orbitofrontal and medial prefrontal
      cortices, but not the anterior cingulate cortex, project to medially situated
      amygdaloid areas such as the cortical and medial nuclei and to the periamygdaloid
      cortex. The agranular and dysgranular insula, the parainsula, and rostral
      portions of the superior temporal gyrus project both to the lateral, basal, and
      accessory basal nuclei and to the medially situated nuclei. Projections to the
      central nucleus are particularly prominent from these regions. These data are
      discussed in relation to the hierarchical processing of sensory information that
      occurs within the amygdaloid complex.

PMID- 12210127
TI  - Clustered distribution of cAMP-dependent protein kinase regulatory isoform RI
      alpha during the development of the rat brain.
AB  - cAMP is a ubiquitous second messenger, which acts mainly through specific protein
      kinases that consist of two regulatory and two catalytic subunits. An unsolved
      problem in cAMP physiology is how it can regulate so many cellular functions
      through this simple enzymatic cascade. A tentative explanation is related to the
      different biochemical properties of the four regulatory subunit isoforms (RI
      alpha and RI beta, RII alpha and RII beta) and to their differential cell and
      tissue distribution. For example, detergent insoluble aggregates of RI alpha are
      present in some cholinergic neurons of the adult rat brain. Rat brains, from the
      embryonic stage to old age, were examined for the presence of highly concentrated
      clusters of RI alpha. They are present only in some neurons of restricted brain
      areas, for a limited time span. During development, labeled neurons appear in
      different brain areas after neuron migration, at a stage of advanced functional
      maturation. They have their greatest expression after birth but before sexual
      maturation, and then they slowly decline, persisting only in a few brain areas
      throughout life. The first appearance, time course, and eventual disappearance is
      different in the different brain areas: RI alpha clusters appear in brainstem,
      hypothalamus, and accessory olfactory bulb at a late embryonic stage; in the main
      olfactory bulb, hippocampus, and medial thalamic nuclei shortly after birth; and
      in the cortex as late as in the third and fourth postnatal week. During the rat's
      lifespan, the distribution of these peculiar RI alpha clusters undergo changes
      that may contribute to shape neuronal responses differentially to agents
      modifying cAMP levels.

PMID- 12210128
TI  - ATP-binding cassette transporter ABCA2 (ABC2) expression in the developing spinal
      cord and PNS during myelination.
AB  - We examined developmental characteristics of the ATP-binding cassette transporter
      ABCA2 (or ABC2) -expressing cells in rat spinal cord and peripheral nerves. In
      adult spinal cord, ABCA2 immunoreactivity was detected in lysosome-like
      organelles of mature oligodendrocyte cell bodies, and a single specific band was
      detected by Western blot analysis. In postnatal developing spinal cord, ABCA2
      immunolabeling was first detected in a small number of cells restricted to the
      ventral marginal area and the dorsal funiculus at birth (P0). ABCA2-positive
      cells were co-immunolabeled by O4, a marker for late progenitor and immature
      oligodendrocytes. At the same time, myelin basic protein was apparent in the same
      restricted regions. The number of ABCA2 and O4 co-immunolabeled cells increased
      quickly in both dorsal and ventral regions from P2 and reached a peak at P8.
      After transient expression from P0 to P8, O4 labeling in white matter tracts
      decreased and disappeared. In contrast, ABCA2-positive oligodendrocytes persisted
      in gray and white matter throughout the spinal cord into adulthood. These data
      suggest a role for the ABCA2 transporter in maturation of oligodendrocyte lineage
      cells and the onset of myelination in the central nervous system. In addition,
      ABCA2 immunoreactivity was detected in the ciliated region of the ependyma in the
      central canal from early postnatal development. ABCA2 immunoreactivity was also
      detected in the Schwann cell lineage in developing spinal nerves and in adult
      trigeminal and sciatic nerves. ABCA2 was also expressed in numerous undetermined
      cells distributed in para-nerve connective tissues and nerve sheaths throughout
      early postnatal development. These data indicate multiple levels of involvement
      for ABCA2 in nervous system development especially with strong evidence for a
      role in myelination.

PMID- 12210129
TI  - Density gradients of trans-synaptically labeled collicular neurons after
      injections of rabies virus in the lateral rectus muscle of the rhesus monkey.
AB  - We evaluated the two-dimensional distribution of superior colliculus (SC) neurons
      visualized after retrograde transneuronal transport of rabies virus injected into
      the lateral rectus muscle of rhesus monkeys to test whether the density of
      projection neurons might play a role in the spatiotemporal transformation and
      vector decomposition. If this were the case, the number of horizontal eye
      movement-related SC neurons should increase with their distance from the rostral
      pole of the SC and decrease with their distance from the representation of the
      horizontal meridian. Labeled neurons of the intermediate SC layers were counted
      inside a 1-mm-wide band that matched the horizontal meridian of the collicular
      motor map. Local areal densities were plotted against distance from the rostral
      SC pole. At 2.5 days after inoculation, there was no labeling in the SC. At 3
      days, moderate labeling appeared on both sides, mostly in the intermediate
      layers. At 3.5 days, cell numbers substantially increased and the laminar
      distribution changed as cells appeared in the superficial SC layers. At 3 days,
      rostrocaudal density profiles were unimodal, with peaks at locations near 50
      degrees (contralateral SC) and 25-30 degrees (ipsilateral SC) horizontal
      eccentricity. At 3.5 days, distributions were bimodal due to the appearance of a
      second high-density region near the rostral pole of the SC. The distribution of
      SC neurons influencing the abducens nucleus, thus, was nonuniform. Caudal sites
      contained more neurons, but the experimentally observed density gradients were
      shallower than the theoretically predicted ones that would be necessary to fully
      account for the spatiotemporal transformation. Similarly, we studied the
      distributions of cell densities in the intermediate SC layers along an
      isoamplitude line (representing saccades of equal amplitudes but different
      directions). Consistent with theoretical estimates of the density gradients
      required for vector decomposition, we found that the concentrations of labeled
      cells were highest in the vicinity of the horizontal meridian but their decrease
      toward the periphery of the motor map was steeper than predicted. We conclude
      that SC cell density gradients cannot fully account for the spatiotemporal
      transformation and vector decomposition in the absence of an additional mechanism
      such as the previously demonstrated (Grantyn et al., [1997] Soc. Neurosci. Abstr.
      23:1295; Moschovakis et al., [1998] J. Neurosci. 18:10219-10229) locus-dependent
      weighting of the strength of efferent projections to the saccade generators.

PMID- 12210130
TI  - Segregation of visual input to the mushroom bodies in the honeybee (Apis
      mellifera).
AB  - Insect mushroom bodies are brain regions that receive multisensory input and are
      thought to play an important role in learning and memory. In most neopteran
      insects, the mushroom bodies receive direct olfactory input. In addition, the
      calyces of Hymenoptera receive substantial direct input from the optic lobes. We
      describe visual inputs to the calyces of the mushroom bodies of the honeybee Apis
      mellifera, the neurons' dendritic fields in the optic lobes, the medulla and
      lobula, and the organization of their terminals in the calyces. Medulla neurons
      terminate in the collar region of the calyx, where they segregate into five
      layers that receive alternating input from the dorsal or ventral medulla,
      respectively. A sixth, innermost layer of the collar receives input from lobula
      neurons. In the basal ring region of the calyx, medulla neuron terminals are
      restricted to a small, distal part. Lobula neurons are more prominent in the
      basal ring, where they terminate in its outer half. Although the collar and basal
      ring layers generally receive segregated input from both optic neuropils, some
      overlap occurs at the borders of the layers. At least three different types of
      mushroom body input neurons originate from the medulla: (a) neurons with narrow
      dendritic fields mainly restricted to the vicinity of the medulla's serpentine
      layer and found throughout the medulla; (b) neurons restricted to the ventral
      half of the medulla and featuring long columnar dendritic branches in the outer
      medulla; and (c) a group of neurons whose dendrites are restricted to the most
      ventral part of the medulla and whose axons form the anterior inferior optic
      tract. Most medulla neurons (groups a and b) send their axons via the anterior
      superior optic tract to the mushroom bodies. Neurons connecting the lobula with
      the mushroom bodies have their dendrites in a defined dorsal part of the lobula.
      Their axons form a third tract to the mushroom bodies, here referred to as the
      lobula tract. Our findings match the anatomy of intrinsic mushroom body neurons
      (Strausfeld, 2002) and together indicate that the mushroom bodies may be composed
      of many more functional subsystems than previously suggested.

PMID- 12210131
TI  - Calcium-binding proteins map the postnatal development of rat vestibular nuclei
      and their vestibular and cerebellar projections.
AB  - We investigated whether three calcium-binding proteins, calretinin, parvalbumin,
      and calbindin, could identify specific aspects of the postnatal development of
      the rat lateral (LVN) and medial (MVN) vestibular nuclei and their vestibular and
      cerebellar connections. Calretinin levels in the vestibular nuclei, increased
      significantly between birth and postnatal day (P) 45. In situ hybridization and
      immunocytochemical staining showed that calretinin-immunoreactive neurons were
      mostly located in the parvocellular MVN at birth and that somatic and dendritic
      growth occurred between birth and P14. During the first week, parvalbumin
      immunoreactive fibers and endings were confined to specific areas, i.e., the
      ventral LVN and magnocellular MVN, and identified exclusively the maturation of
      the vestibular afferents. Calbindin was located within the dorsal LVN and the
      parvocellular MVN and identified the first arrival of the corticocerebellar
      afferents. From the second week, in addition to labeling vestibular afferents in
      their specific target areas, parvalbumin was also found colocalized with
      calbindin in mature Purkinje cell afferents. Thus, the specific spatiotemporal
      distribution of parvalbumin and calbindin could correspond to two successive
      phases of synaptic remodeling involving integration of the vestibular sensory
      messages and their cerebellar control. On the basis of the sequence of
      distribution patterns of these proteins during the development of the vestibular
      nuclei, calretinin is an effective marker for neuronal development of the
      parvocellular MVN, parvalbumin is a specific marker identifying maturation of the
      vestibular afferents and endings, and calbindin is a marker of the first
      appearance and development of Purkinje cell afferents.

PMID- 12210132
TI  - Distribution of calbindin D-28k in the entorhinal, perirhinal, and
      parahippocampal cortices of the macaque monkey.
AB  - We examined the distribution of calbindin D-28k-immunoreactive (CB-IR) neurons,
      fibers, and neuropil in the entorhinal (area 28), perirhinal (areas 35 and 36),
      and parahippocampal (areas TH and TF) cortices in the macaque monkey. Two main
      findings are reported. First, except for CB-IR neurogliaform cells that are only
      observed in the parahippocampal cortex, the morphology of CB-stained pyramidal
      and nonpyramidal cells were similar across the three cortical areas examined.
      Second, we find that the topography of CB staining differed between the three
      areas. The entorhinal cortex exhibits the most striking gradient of CB staining
      such that the most anterior and medial portions are most strongly labeled,
      whereas posterior and lateral areas exhibit only weak labeling. The labeling
      throughout the perirhinal and parahippocampal cortices is more homogeneous. Area
      35 contains only lightly stained neuropil and few CB-IR cells. Area 36 and areas
      TH and TF of the parahippocampal cortex contain a moderate to high density of CB
      IR cells and fibers throughout their full rostrocaudal extents, although each
      area exhibits unique laminar patterns of staining. In all areas examined, the
      highest density of CB-positive cells and fibers is observed in superficial layers
      with lower densities of CB-positive cells and fibers present in deep layers.
      These findings, taken together with our current understanding of the connections
      of these areas may have implications for understanding the circuit properties of
      the entorhinal, perirhinal, and parahippocampal cortices areas in both normal and
      disease states.

PMID- 12210133
TI  - Correlation between CGRP immunoreactivity and firing activity in cat abducens
      motoneurons.
AB  - A relationship between motoneuron activity and calcitonin gene-related peptide
      (CGRP) expression was previously suggested based on indirect inferences. We show
      here a positive correlation between CGRP immunoreactivity and firing activity in
      an experimental model that used tetanus neurotoxin (TeNT) to alter basal firing
      levels. A low dose (0.5 ng/kg) of TeNT injected in the lateral rectus muscle
      raised the basal firing rate of ipsilateral abducens motoneurons, estimated as
      the firing rate at straight-ahead gaze (F(0)); the firing rate returned to
      control values after 2 weeks. In contrast, a high dose (5 ng/kg) of TeNT
      decreased basal firing, which recovered slowly over a 7-week period. Expression
      of CGRP immunoreactivity by abducens motoneurons, preferentially related to
      betaCGRP gene expression, was analyzed during these periods of altered firing
      activity. The number of CGRP-immunofluorescent abducens motoneurons increased to
      approximately 120% by 7 days after low-dose TeNT, to include all available
      motoneurons in the nucleus. In addition, the average CGRP immunofluorescence
      optical density inside motoneurons almost doubled after 4 days and returned
      toward control values in the following 2 weeks. In contrast, a high-dose
      injection of TeNT reduced the number of CGRP-immunofluorescent motoneurons to
      5.4% of control 7 days post injection, and the number returned to 77.6% after 42
      days. CGRP immunofluorescence intensity inside motoneurons was also reduced.
      Regression analysis of F(0) values with either the number of CGRP-immunolabeled
      motoneurons, their average immunofluorescence intensity, or both factors combined
      resulted in positive correlations with regression coefficients of 0.87 or higher.
      Therefore, CGRP expression and firing activity in abducens motoneurons are
      positively correlated.

PMID- 12210135
TI  - Genetic influences on secondary degeneration and wound healing following spinal
      cord injury in various strains of mice.
AB  - Various inbred strains of mice exhibit dramatic differences in sensitivity to
      excitotoxic cell death induced by systemic injections of kainic acid (KA). The
      present study evaluates whether the same strains are also differentially
      sensitive to secondary degeneration after spinal cord injury, in which
      excitotoxic cell death is thought to play a pathogenic role. Spinal cord crush
      injuries were produced at T9 in two inbred strains that are resistant to KA
      induced excitotoxic cell death (C57Bl/6 and Balb/c) and four strains that are
      sensitive (CD-1, FVB/N, 129T2 Sv/EMS, and C57Bl/10). The spinal cord was prepared
      for light microscopy at intervals from 1 to 56 days postinjury, and the area of
      damaged tissue (termed lesion size) and amount of cavitation were determined by
      quantitative image analysis. Lesion size increased between 1 and 7 days in all
      strains and then decreased steadily in a wound-healing process that occurs
      uniquely in mice. The extent of cavitation also gradually decreased from 7 to 56
      days in all strains. Although lesion area and cavitation decreased in all
      strains, there were significant differences in lesion size and cavitation across
      strains. Specifically, lesion areas in the KA-sensitive strains FVB/N, 129T2
      Sv/EMS, and CD-1 were significantly larger at 56 days postinjury than in the KA
      resistant strains C57Bl/6 and Balb/c. We conclude that the genetic differences
      that confer resistance and sensitivity to KA-induced neurotoxicity also modify
      the secondary degenerative processes that occur after spinal cord injury, so that
      resistance to excitotoxic injury leads to smaller overall lesions and a more
      effective wound-healing response.

PMID- 12210134
TI  - Characterization of the optic nerve and retinal ganglion cell layer in the
      dysmyelinated adult Long Evans Shaker rat: evidence for axonal sprouting.
AB  - Myelin in the central nervous system (CNS) is hypothesized to help guide the
      growth of developing axons by inhibiting sprouting of aberrant neurites. Previous
      studies using animal models lacking CNS myelin have reported that increasing
      capacity for sprouting axons is negatively correlated with the degree of
      myelination. In the present study, we investigated the optic nerves of the
      recently identified Long Evans Shaker (LES) rat with prolonged dysmyelination of
      adult axons to determine whether the lack of myelin basic protein (MBP) in adult
      LES rats could manifest as increases in the population of CNS axons. We observed
      numerous small, unmyelinated axon profiles (<0.3 microm in diameter) clustered in
      bundles alongside normal caliber axons in dysmyelinated LES rats but not in
      normal myelinated Long Evans (LE) rats. These putative axon profiles resembled
      sprouting axons previously described in the CNS. Moreover, the high number of
      small putative axon profiles could not be accounted for by any significant
      increases in the number of ganglion cells and displaced amacrine cells in the
      ganglion cell layer when compared with normal rats as evaluated by using a
      variety of techniques. This finding suggests that the observed clusters of
      putative axon profiles were not due to developmental abnormalities in the retina
      but to the lack of myelin in the optic nerves of LES rats. The adult LES rat,
      therefore, may serve as a useful model to study the role of myelin in regulating
      axon development or axon regeneration after CNS injury in the adult mammalian
      system.

PMID- 12210136
TI  - Projections from the amygdaloid complex to the claustrum and the endopiriform
      nucleus: a Phaseolus vulgaris leucoagglutinin study in the rat.
AB  - The claustrum and the endopiriform nucleus contribute to the spread of
      epileptiform activity from the amygdala to other brain areas. Data of the
      distribution of pathways underlying the information flow between these regions
      are, however, incomplete and controversial. To investigate the projections from
      the amygdala to the claustrum and the endopiriform nucleus, we injected the
      anterograde tracer Phaseolus vulgaris leucoagglutinin into various divisions of
      the amygdaloid complex, including the lateral, basal, accessory basal, central,
      anterior cortical and posterior cortical nuclei, the periamygdaloid cortex, and
      the amygdalohippocampal area in the rat. Analysis of immunohistochemically
      processed sections reveal that the heaviest projections to the claustrum
      originate in the magnocellular division of the basal nucleus. The projection is
      moderate in density and mainly terminates in the dorsal aspect of the anterior
      part of the claustrum. Light projections from the parvicellular and intermediate
      divisions of the basal nucleus terminate in the same region, whereas light
      projections from the accessory basal nucleus and the lateral division of the
      amygdalohippocampal area innervate the caudal part of the claustrum. The most
      substantial projections from the amygdala to the endopiriform nucleus originate
      in the lateral division of the amygdalohippocampal area. These projections
      terminate in the central and caudal parts of the endopiriform nucleus. Lighter
      projections originate in the anterior and posterior cortical nuclei, the
      periamygdaloid cortex, the medial division of the amygdalohippocampal area, and
      the accessory basal nucleus. These data provide an anatomic basis for recent
      functional studies demonstrating that the claustrum and the endopiriform nucleus
      are strategically located to synchronize and spread epileptiform activity from
      the amygdala to the other brain regions. These topographically organized pathways
      also provide a route by means of which the claustrum and the endopiriform nucleus
      have access to inputs from the amygdaloid networks that process emotionally
      significant information.

PMID- 12210137
TI  - Acoustic trauma induces reemergence of the growth- and plasticity-associated
      protein GAP-43 in the rat auditory brainstem.
AB  - We explored the consequences of unilateral acoustic trauma to intracochlear and
      central nervous system structures in rats. An acoustic trauma, induced by
      applying click stimuli of 130 dB (sound pressure level; SPL) for 30 minutes,
      resulted in an instant and permanent threshold shift of 95.92 +/- 1.08 dB (SEM)
      in the affected ear. We observed, as a consequence, a structural deterioration of
      the organ of Corti. Deprivation-dependent changes of neurons of the auditory
      brainstem were determined using antibodies against neurofilament and the growth
      associated protein GAP-43 and compared with those following cochleotomy, studied
      earlier. By 231 days posttrauma, spiral ganglion cell bodies and their processes
      were almost entirely lost from all cochlear regions with destroyed organ of
      Corti. In the lateral superior olive (LSO) ipsilateral to the trauma, cell bodies
      of lateral olivocochlear neurons turned transiently GAP-43 positive within the
      first 1.5 years posttrauma. The time course of emergence and disappearance of
      this population of neurons was similar to that found after cochleotomy.
      Additionally, after noise trauma, principal cells in contralateral LSO and in
      medial superior olive (MSO) on both sides of the brainstem developed an
      expression of GAP-43 that began 3 and 16 days posttrauma, respectively, and
      lasted for at least 1 year. Such cells were rarely observed after cochleotomy. An
      unequivocal rise in GAP-43 immunoreactivity was also found in the neuropil of the
      inferior colliculus and the ventral cochlear nucleus, both preferentially on the
      acoustically damaged side. We conclude that the degree and specific cause of
      sudden unilateral deafness entail specific patterns of plasticity responses in
      the auditory brainstem, possibly to prevent the neural network dedicated to
      locate sounds in the environment from delivering erroneous signals centralward.

PMID- 12210138
TI  - BMP mRNA and protein expression in the developing mouse olfactory system.
AB  - The bone morphogenetic proteins (BMPs) play fundamental roles during the
      organization of the central nervous system. The presence of these proteins has
      also been demonstrated in regions of the adult brain that are characterized by
      neural plasticity. In this study, we examined the expression of BMP4, 6, and 7
      mRNAs and proteins in the murine olfactory system. The olfactory system is a
      useful model for studying cell proliferation and neural differentiation because
      both of these processes persist throughout life in the olfactory epithelium (OE)
      and olfactory bulb (OB). Our results demonstrate a differential expression of
      BMP4, 6, and 7 in the embryonic, postnatal, and adult olfactory system. In
      particular, BMP4 and BMP7 showed similar immunostaining patterns, being expressed
      in the olfactory region from the earliest stages studied (embryonic day 15.5) to
      adulthood. During development BMPs were expressed in the OE, olfactory bulb nerve
      layer, glomerular layer (GL), mitral cell layer (MCL), and subventricular zone.
      During the first postnatal week of life, BMP4 and 7 immunoreactivity (-ir) was
      particularly evident in the GL, MCL, and in the subependymal layer (SEL), which
      originates postnatally from the subventricular zone. In adults, BMP4 and 7
      immunostaining was present in the GL and SEL. Within the SEL, BMP4 and 7 proteins
      were expressed primarily in association with the astrocytic glial compartment.
      BMP6-ir was always found in mature olfactory receptor neurons and their axonal
      projections to the OB. In summary, these data support the hypothesis that BMPs
      play a role in the morphogenesis of the olfactory system during development and
      in its plasticity during adulthood.

PMID- 12210139
TI  - In Patas monkey, glutamic acid decarboxylase-67 and reelin mRNA coexpression
      varies in a manner dependent on layers and cortical areas.
AB  - In nonhuman and human primates, reelin immunoreactivity is expressed consistently
      in gamma-aminobutyric acid (GABA)-ergic interneurons of the three upper cortical
      layers (Impagnatiello et al. [1998] Proc. Natl. Acad. Sci. U S A 95:15718-15723;
      Rodriguez et al. [2000] Proc. Natl. Acad. Sci. U S A 97:3550-3555). To understand
      in detail the pattern of reelin synthesis in GABAergic interneurons of primate
      neocortex, a quantitative analysis of reelin and of glutamic acid decarboxylase
      67 (GAD(67)) mRNA-positive neurons as well as a quantitative analysis of total
      neuronal density measured by neuron-specific nuclear protein (NeuN)
      immunoreactivity was carried out in Patas monkey neocortex (Brodmann's areas 2,
      3, 4, 6, 9, 17, 18, and 24). Reelin mRNA is expressed in every cortical area and
      layer studied, but layer II of each cortical area consistently revealed the
      largest neuronal population expressing reelin mRNA compared with other layers.
      The percentages of GAD(67)-positive neurons in each layer of the eight cortical
      areas were 83-98% in layer I, 55-64% in layer II, 37-49% in layer III, 71-89% in
      layer IV, 54-68% in layer V, and 71-85% in layer VI. The percentages of GABAergic
      neurons expressing reelin were 86-100% in layer I, 76-84% in layer II, 52-96% in
      layer III, 23-33% in layer IV, 33-57% in layer V, and 34-54% in layer VI. These
      findings suggest that there may be two classes of GABAergic neurons that can be
      differentiated by their ability to express reelin mRNA and reelin protein. This
      differentiation may have a functional significance, considering that reelin is
      secreted into the extracellular matrix, where it plays a putative role in the
      maturation of newly formed dendritic spines and binds selectively to dendritic
      shafts and to spine postsynaptic densities and presumably to integrin receptors,
      including alpha(3) subunits (Rodriguez et al. [2000]).

PMID- 12210140
TI  - Expression of Vema in the developing mouse spinal cord and optic chiasm.
AB  - A critical phase of nervous system development is the formation of connections
      between axons and their synaptic targets. Intermediate targets play important
      roles in axon pathfinding by supplying growing axons with long- and short- range
      guidance cues at decision points along their trajectory. We recently identified
      Vema as a novel membrane-associated protein that is expressed at the ventral
      midline of the developing vertebrate central nervous system (CNS). We report that
      Vema is expressed in the floor plate, an intermediate target for pathfinding
      commissural axons located at the ventral midline of the developing mouse spinal
      cord. Interestingly, Vema expression overlaps with the position of an unique
      population of neurons situated at the midline of the ventral diencephalon and
      that function as intermediate targets for pathfinding retinal ganglion cell
      axons. The distribution of Vema in the developing spinal cord and optic chiasm
      resembles the expression patterns of a variety of molecules known to play
      important roles in axon guidance, including Robo2, Neuropilin2, and SSEA. The
      expression of Vema at two key choice points for pathfinding axons suggests an
      important role for this protein in regulating axon guidance at the midline of the
      developing mouse central nervous system.

PMID- 12210141
TI  - MEK inhibitor U0126 interferes with immunofluorescence analysis of apoptotic cell
      death.
AB  - BACKGROUND: Binding of extracellular growth factors to cell surface receptors
      often results in activation of the mitogen-activated protein kinase (MAPK). MAPK
      is regulated by MAPK kinase, also called MEK. Deprivation of growth factors
      during cell culture or intracellular MEK inhibition leads to inhibition of
      proliferation and apoptotic cell death. Besides other techniques, apoptotic cells
      can be identified by phosphatidylserine (PS) exposure and exclusion of membrane
      impermeant propidium iodide (PI). We investigated the limitations of detection of
      apoptotic cell death and cytofluorometry in cells cultured in the presence of the
      MEK inhibitor U0126. METHODS: Apoptotic cell death was induced in the
      plasmacytoma cell line INA-6, in peripheral blood mononuclear cells (PBMC), and
      in cultured T lymphoblasts by deprivation of interleukin-6 (IL-6) or by
      incubation with the MEK inhibitor U0126. Apoptotic cell death was quantified by
      flow cytometry using annexin V/propidium iodide (AxV/PI) double staining.
      RESULTS: U0126-treated cells dramatically changed their fluorescence pattern
      during cell culture. If AxV/PI staining is employed to detect apoptotic cell
      death, the background fluorescence mimicks PS exposure on viable cells. The
      compound itself has no intrinsic fluorescence in vitro but develops an intensive
      fluorescence during cell culture which can be observed in all fluorescence
      channels with a predominance in the FL1 channel (525 nm). We further demonstrate
      that at least some of the U0126-induced background fluorescence is dependent on
      cellular uptake and intracellular modifications or cellular responses.
      CONCLUSIONS: These results demonstrate that appropriate controls for every single
      time point are necessary if fluorescence analyses are performed in the presence
      of chemical enzyme inhibitors. In the case of MEK inhibitors, either the use of
      PD098059 or PD184352 as an alternative for U0126 or nonfluorometric methods for
      detection of apoptosis should be considered.

PMID- 12210142
TI  - Apoptotic rate: a new indicator for the quantification of the incidence of
      apoptosis in cell cultures.
AB  - BACKGROUND: Late apoptotic cells divide into apoptotic bodies and are missed by
      current detection methods. This results in an artificially low apoptotic index
      (AI). METHODS: This study proposes a flow cytometry-based ratiometric method that
      uses an internal reference standard of microbeads combined with fluorescein
      annexin V binding and 7-aminoactinomycin D to enumerate viable, necrotic, and
      early and late apoptotic cells within specific subsets of a heterogeneous
      culture. RESULTS: In the absence of cell growth, the number of apoptotic cells
      that undergo fragmentation into apoptotic bodies in culture can also be
      determined accurately by this method. This information can then be used to obtain
      the apoptotic rate (AR), a new indicator of apoptosis that calculates the
      proportion of cells that have undergone apoptosis with respect to the total
      number of seeded cells. The main limitation of the method is that the AR is only
      suitable for the study of apoptosis in noncycling cells. CONCLUSIONS: This study
      reveals the superiority of the proposed method over the widely used Nicoletti
      method and current annexin-V binding methods. The AI did not reflect the true
      incidence of lymphocyte apoptosis, neither in response to lectins or phorbol
      esters, nor to serum deprivation. AR was more sensitive than AI, detecting
      apoptosis at lower concentrations of cell death inducers in all the subsets
      studied.

PMID- 12210143
TI  - Small aggregates of platelets can be detected sensitively by a flow cytometer
      equipped with an imaging device: mechanisms of epinephrine-induced aggregation
      and antiplatelet effects of beraprost.
AB  - BACKGROUND: Although cross-talks between platelets and other blood cells are
      important in vivo, laboratory platelet aggregation tests have been performed
      mainly with the use of platelet-rich plasma (PRP) as samples. Methods that enable
      an efficient and sensitive detection of platelet aggregates in whole blood are
      being developed. METHODS: A flow cytometer equipped with an imaging device, the
      flow imaging cytometer 2 (FIC2), was used to detect platelet aggregates in whole
      blood. RESULTS: The FIC2 provides a resolution that is high enough to
      differentiate platelet aggregates from single platelets or other blood cells.
      Epinephrine elicited platelet aggregate formation in hirudin plus argatroban
      treated whole blood, but not in PRP. The reconstitution study revealed that a
      small amount of adenosine diphosphate (ADP) from erythrocytes may play an
      important role in epinephrine-induced platelet aggregation (in whole blood),
      through mediation of P2Y1 receptors. When the inhibitory effect of beraprost, an
      antiplatelet agent, on platelet aggregation was assessed, analysis of whole blood
      samples with FIC2 proved to be the most sensitive among the methods available.
      CONCLUSIONS: FIC2 is a promising device for detection of platelet aggregates in
      whole blood, with wide basic and clinical applications.

PMID- 12210144
TI  - Karyotyping of comparative genomic hybridization human metaphases using kernel
      nearest-neighbor algorithm.
AB  - BACKGROUND: Comparative genomic hybridization (CGH) is a relatively new molecular
      cytogenetic method that detects chromosomal imbalances. Automatic karyotyping is
      an important step in CGH analysis because the precise position of the chromosome
      abnormality must be located and manual karyotyping is tedious and time-consuming.
      In the past, computer-aided karyotyping was done by using the 4',6-diamidino-2
      phenylindole, dihydrochloride (DAPI)-inverse images, which required complex image
      enhancement procedures. METHODS: An innovative method, kernel nearest-neighbor (K
      NN) algorithm, is proposed to accomplish automatic karyotyping. The algorithm is
      an application of the "kernel approach," which offers an alternative solution to
      linear learning machines by mapping data into a high dimensional feature space.
      By implicitly calculating Euclidean or Mahalanobis distance in a high dimensional
      image feature space, two kinds of K-NN algorithms are obtained. New feature
      extraction methods concerning multicolor information in CGH images are used for
      the first time. RESULTS: Experiment results show that the feature extraction
      method of using multicolor information in CGH images improves greatly the
      classification success rate. A high success rate of about 91.5% has been
      achieved, which shows that the K-NN classifier efficiently accomplishes automatic
      chromosome classification from relatively few samples. CONCLUSIONS: The feature
      extraction method proposed here and K-NN classifiers offer a promising
      computerized intelligent system for automatic karyotyping of CGH human
      chromosomes.

PMID- 12210145
TI  - Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in
      vitro: potential therapeutic use in the treatment of inflammatory bowel disease.
AB  - BACKGROUND: Cytokines involved in inflammatory bowel disease (IBD) direct a
      predominantly cell-mediated T- helper-1 (Th1) immune response. The nonspecific
      anti-inflammatory treatment being used in the management of patients with IBD has
      not changed much since the 1970s and new therapeutic agents are keenly sought.
      Several compounds isolated from Allium sativum (garlic) modulate leukocyte cell
      proliferation and cytokine production. METHODS: To investigate the possible
      therapeutic effects of garlic in the treatment of patients with IBD, whole blood
      and peripheral blood mononuclear cells (PBMCs) were stimulated in the presence of
      various concentrations of garlic extract and the effect on leukocyte cytokine
      production was determined in vitro using multiparameter flow cytometry. RESULTS:
      Monocyte interleukin (IL)-12 production was inhibited significantly in the
      presence of low concentrations of garlic extract (>or=0.1 microg/ml total
      protein). Monocyte IL-10 production increased significantly and monocyte tumor
      necrosis factor-alpha (TNF-alpha), IL-1alpha, IL-6, IL-8, T-cell interferon-gamma
      (IFN-gamma), IL-2, and TNF-alpha decreased significantly in the presence of
      >or=10 microg/ml garlic extract. Twenty to fifty percent of the immunomodulatory
      activity of garlic extract on cytokine production was acid labile. The inhibitory
      activity of methylprednisolone, a commonly used anti-inflammatory in IBD, with
      garlic on leukocyte cytokine production was additive. CONCLUSIONS: By inhibiting
      Th1 and inflammatory cytokines while upregulating IL-10 production, treatment
      with garlic extract may help to resolve inflammation associated with IBD. An in
      vivo animal model study needs to be undertaken to determine the significance of
      these in vitro findings.

PMID- 12210146
TI  - Structure and dynamics of liquid water with different long-range interaction
      truncation and temperature control methods in molecular dynamics simulations.
AB  - We have used molecular dynamics simulations to study the physical properties of
      modified TIP3P water model included in the CHARMM program, using four different
      methods-the Ewald summation technique, and three different spherical truncation
      methods-for the treatment of the long-range interactions. Both the structure and
      dynamics of the liquid water model were affected by the methods used to truncate
      the long-range interactions. For some of the methods artificial structuring of
      the model liquid was observed around the cutoff radius. The model liquid
      properties were also affected by the commonly applied temperature control
      methods. Four different methods for controlling the temperature of the system
      were studied, and the effects of these methods on the bulk properties for liquid
      water were analyzed. The system size was also found to change the dynamics of the
      model liquid water. Two control simulations with the SPC/E water model were
      carried out. The self-diffusion coefficient (D), the radial distribution function
      (g(OO)), the distance dependent Kirkwood G-factor [G(k)(r)] and the
      intermolecular potential energy (E(pot)) were determined from the different
      trajectories and compared with the experimental data.

PMID- 12210147
TI  - A comparison of predicted and experimental vibrational spectra in some small
      fluorocarbons.
AB  - The vibrational assignments of difluoromethane, cis and trans 1,2
      difluoroethylene, trifluoroethylene, 2-fluoropropene, 1,1-difluoroethylene, and
      tetrafluoroethylene have been reassessed in the light of recent theoretical work.
      Inconsistent experimental wave number values and assignments have been clarified,
      and some changes to the experimental assignments are proposed. The assignments
      compare favorably with recent scaled density functional theory calculations using
      the hybrid three-parameter B3-PW91 density functional.

PMID- 12210148
TI  - Stable conformations of 12-crown-O3N and its Li+ complex in aqueous solution.
AB  - Stable conformations of 12-crown-O3N and its Li complexes in aqueous solution
      were investigated. To calculate the free energy differences of conformers of 12
      crown-O3N and its Li+ complex, our procedure was to make use of two programs,
      CONFLEX and BOSS. The former generates conformers, and the latter calculates the
      differences in free energy of solvation between two conformers in aqueous
      solution. It was confirmed that the present procedure is applicable in solving
      the question of what is the most stable conformation of 12-crown-O3N in aqueous
      solution. Results of the calculations suggest that the order of stability for
      conformers in a vacuum is different from that in aqueous solution. It was also
      confirmed that the coordination geometry of solvent waters to Li+ changes
      depending on the distance between the cation and the crown ring.

PMID- 12210149
TI  - Carbohydrate solution simulations: producing a force field with experimentally
      consistent primary alcohol rotational frequencies and populations.
AB  - We present a CHARMM Carbohydrate Solution Force Field (CSFF) suitable for
      nanosecond molecular dynamics computer simulations. The force field was derived
      from a recently published sugar parameter set.1 Dihedral angle parameters for the
      primary alcohol as well as the secondary hydroxyl groups were adjusted. Free
      energy profiles of the hydroxymethyl group for two monosaccharides (beta-D
      glucose and beta-D-galactose) were calculated using the new parameter set and
      compared with similar force fields. Equilibrium rotamer populations obtained from
      the CSFF are in excellent agreement with NMR data (glucose gg:gt:tg approximately
      66:33:1 and galactose gg:gt:tg approximately 4:75:21). In addition, the primary
      alcohol rotational frequency is on the nanosecond time scale, which conforms to
      experimental observations. Equilibrium population distributions of the primary
      alcohol conformers for glucose and galactose are reached within 10 nanoseconds of
      molecular dynamics simulations. In addition, gas phase vibrational frequencies
      computed for beta-D-glucose using this force field compare well with experimental
      frequencies. Carbohydrate parameter sets that produce both conformational
      energies and rotational frequencies for the pyranose primary alcohol group that
      are consistent with experimental observations should allow for increased accuracy
      in modeling the flexibility of biologically important (1-6)-linked saccharides in
      solution.

PMID- 12210150
TI  - Accelerated Poisson-Boltzmann calculations for static and dynamic systems.
AB  - We report here an efficient implementation of the finite difference Poisson
      Boltzmann solvent model based on the Modified Incomplete Cholsky Conjugate
      Gradient algorithm, which gives rather impressive performance for both static and
      dynamic systems. This is achieved by implementing the algorithm with Eisenstat's
      two optimizations, utilizing the electrostatic update in simulations, and
      applying prudent approximations, including: relaxing the convergence criterion,
      not updating Poisson-Boltzmann-related forces every step, and using electrostatic
      focusing. It is also possible to markedly accelerate the supporting routines that
      are used to set up the calculations and to obtain energies and forces. The
      resulting finite difference Poisson-Boltzmann method delivers efficiency
      comparable to the distance-dependent dielectric model for a system tested, HIV
      Protease, making it a strong candidate for solution-phase molecular dynamics
      simulations. Further, the finite difference method includes all intrasolute
      electrostatic interactions, whereas the distance dependent dielectric
      calculations use a 15-A cutoff. The speed of our numerical finite difference
      method is comparable to that of the pair-wise Generalized Born approximation to
      the Poisson-Boltzmann method.

PMID- 12210151
TI  - Determination of the effective dielectric constant from the accurate solution of
      the Poisson equation.
AB  - Constant dielectric (CD) and distance-dependent dielectric (DDD) functions are
      the most popular and widespread in the Molecular Mechanics simulations of large
      molecular systems. In this article, we present a simple procedure to derive an
      effective dielectric constant, epsilon (out,eff), for these two methods based on
      numerical solutions of the Poisson equation. It was found that because of the
      very approximate nature of the CD and DDD models there is no universal epsilon
      (out,eff), which will work equally well for all molecular systems. For example,
      different MD trajectories of the same molecule can produce different optimal
      epsilon (out,eff)s. The DDD function was found to yield better agreement with the
      numerical solutions of the Poisson equation than a CD model does. The reason is
      that a DDD function gives a better description of the electrostatic interactions
      at short distances between the atoms. Another interesting finding of this study
      is that under certain conditions epsilon (out,eff) can take negative values for a
      system of two atoms at a limited distance range. However, in principle, there is
      nothing to prevent the epsilon (out,eff) from taking negative values for specific
      conformations of some molecules.

PMID- 12210152
TI  - Mechanistic aspects of the dehydration and dehydrohalogenation of halo
      hydroxyformaldoxime conformers. A quantum chemical model study.
AB  - A detailed exploration of the configurational and conformational space of chloro-
      and bromo-hydroxyformaldoximes, Xhfaox (X = Cl, Br) has been carried out with the
      aid of the B3LYP level of density functional theory, using the 6-31G(d,p) basis
      set. The most stable configuration in each series of the Clhfaox and Brhfaox
      conformers corresponds to the Z-s-cis, s-trans configuration, while the highest
      energy Z-(s-trans, s-cis) conformers were found at 7.0(7.6) and 6.0(6.6) kcal
      mol(-1), respectively, at the B3LYP(QCISD(T)) levels of theory. Saddle points
      were also located on the PES of the Clhfaox and Brhfaox compounds corresponding
      to Z-(s-cis, s-cis) conformers at 13.8(14.9) and 13.6(14.6) kcal mol(-1),
      respectively, at the B3LYP(QCISD(T)) levels. Upon dehydration Xhfaox could afford
      a number of isomeric CXNO species. The dehydration processes of Xhfaox are
      predicted to be endothermic, the computed heats of reactions found in the range
      of 20.5 to 86.2 kcal mol(-1) and 15.9 to 100.4 kcal mol(-1) at the B3LYP and
      QCISD(T) levels, respectively. The reaction pathways for the addition of water to
      halo-fulminates yielding the most stable Xhfaox conformers was predicted to be
      concerted with a single transition structure, but are asynchronous with
      activation barriers of 32.8 and 43.0 kcal mol(-1) for the chloro- and bromo
      derivatives, respectively. The PES governing the isomerization reactions of the
      CXNO isomers have also been calculated, and possible isomerization pathways have
      been delineated. Upon dehydrohalogenation the Xhfaox conformers yield hydroxy
      isocyanate or hydroxy-fulminate, the former being more stable by 31.8(18.8) kcal
      mol(-1) at the B3LYP(QCISD(T)) levels of theory. The reaction pathways for the
      addition of HX to hydroxy-isocyanate were predicted to be slightly exothermic,
      the heats of reactions being -3.2 and -5.5 kcal mol(-1), respectively, and have
      to surmount high activation barriers of 39.7 and 35.0 kcal mol(-1), respectively.
      Similarly, the addition of HX to hydroxy-fulminate was predicted to be much more
      exothermic, the heats of reactions being -34.7 and -37.3 kcal mol(-1),
      respectively, and have to surmount much lower activation barriers of only 10.5
      and 7.5 kcal mol(-1) respectively, at the B3LYP level. Finally, calculated
      structures, relative stability, and bonding properties of all stationary points
      located on the PES of the systems and reactions studied are thoroughly discussed
      with respect to computed electronic properties.

PMID- 12210153
TI  - Binding of D- and L-captopril inhibitors to metallo-beta-lactamase studied by
      polarizable molecular mechanics and quantum mechanics.
AB  - The bacterial Zn2+ metallo-beta-lactamase from B. fragilis is a zinc-enzyme with
      two potential metal ion binding sites. It cleaves the lactam ring of antibiotics,
      thus contributing to the acquired resistance of bacteria against antibiotics. The
      present study bears on the binuclear form of the enzyme. We compare several
      possible binding modes of captopril, a mercaptocarboxamide inhibitor of several
      zinc-metalloenzymes. Two diastereoisomers of captopril were considered, with
      either a D- or an L-proline residue. We have used the polarizable molecular
      mechanics procedure SIBFA (Sum of Interactions Between Fragments ab initio
      computed). Two beta-lactamase models were considered, encompassing 104 and 188
      residues, respectively. The energy balances included the inter and intramolecular
      interaction energies as well as the contribution from solvation computed using a
      continuum reaction field procedure. The thiolate ion of the inhibitor is binding
      to both metal ions, expelling the bridging solvent molecule from the uncomplexed
      enzyme. Different competing binding modes of captopril were considered, either
      where the inhibitor binds in a monodentate mode to the zinc cations only with its
      thiolate ion, or in bidentate modes involving additional zinc binding by its
      carboxylate or ketone carbonyl groups. The additional coordination by the
      inhibitor's carboxylate or carbonyl group always occurs at the zinc ion, which is
      bound by a histidine, a cysteine, and an aspartate side chain. For both
      diastereomers, the energy balances favor monodentate binding of captopril via S-.
      The preference over bidentate binding is small. The interaction energies were
      recomputed in model sites restricted to captopril, the Zn2+ cations, and their
      coordinating end side chains from beta-lactamase (98 atoms). The interaction
      energies and their ranking among competing arrangements were consistent with
      those computed by ab initio HF and DFT procedures.

PMID- 12210158
TI  - Electrophoretic capture of circular DNA in gels.
AB  - Results on electrophoretic capture of circular DNA in porous gels are reviewed.
      Processes which cause arrest of circular forms of DNA during electrophoresis can
      provide very efficient separation mechanism for the purification of plasmids and
      bacterial artificial chromosomes if the corresponding linear form is not trapped
      and therefore removed by the electric field. Two types of such topological traps
      have been proposed, impalement and lobster traps, and we here review the present
      experimental support for the existence of these two circle-specific mechanisms.
      Experiments designed to characterize the traps are discussed, regarding the
      concentration of the traps as well as their efficiency and capacity to trap both
      relaxed and supercoiled circular DNA. Studies of the dynamics of the capture
      process show that the average capture time is on the order of 10 s at 20 V/cm, by
      which time the circles have migrated several hundred micrometers and have passed
      hundreds of traps. We also review results on attempts to improve the capacity and
      efficiency of the trapping process by modification of the gels either by
      enzymatic treatment or by cogelation of neutral polymers.

PMID- 12210159
TI  - Lattice models of DNA electrophoresis.
AB  - This article presents an overview of lattice polymer models used to study DNA
      electrophoresis. Three commonly used models--the bond fluctuation model, the cage
      model, and the repton model--are discussed, as well their extension to include
      electric fields, and simulation results obtained. Physical properties that are
      shared amongst these models are identified, and differences between the models
      are discussed.

PMID- 12210160
TI  - Strategies for dielectrophoretic separation in laboratory-on-a-chip systems.
AB  - Dielectrophoresis--the induced motion of polarizable particles in nonuniform
      fields--has proven to be an effective method for the separation of bioparticles
      such as cells, viruses and proteins. In this paper, the application of
      dielectrophoresis in miniaturized laboratories-on-a-chip is discussed, and
      strategies are described for using dielectrophoresis both for the binary
      separation of bioparticles and for the fractionation of many populations in such
      devices.

PMID- 12210161
TI  - Single molecule measurements of DNA transport through a nanopore.
AB  - We examined the voltage-driven movement of single-stranded DNA molecules in a
      membrane channel or "nanopore". Using single channel recording methods and a
      statistical analysis of many single molecule events, we determined how voltage
      influences capture and translocation in the nanopore. We verified that the mean
      time between capture events follows a simple exponential distribution, whereas
      the translocation times follow a unique distribution that is partly Gaussian and
      partly exponential. Measurements of polymer sequence effects demonstrated that
      translocation duration is heavily influenced by specific or nonspecific purine
      channel interactions. The single molecule approach we used revealed molecular
      interactions that can influence both capture rates and translocation velocities
      in a manner that enriches naive barrier crossing models.

PMID- 12210162
TI  - Evaluation of nanopores as candidates for electronic analyte detection.
AB  - In an effort to increase throughput and decrease the cost of electrophoretic
      separation of DNA and proteins, various groups are developing highly parallel,
      miniaturized separation devices based on capillaries etched into silicon, glass
      or plastic substrates. To date, these miniaturized devices have relied on optical
      detectors, thus placing a lower limit on instrument size, and complicating the
      incorporation of an entire DNA analyzer instrument on a chip. To address this
      limitation, we are evaluating nanopores as candidate Coulter counters for purely
      electronic detection of analytes in miniaturized electrophoresis and similar
      separation devices. To establish feasibility of this detection scheme, we have
      investigated the detection sensitivity of a nanopore sensor through experiments
      with the alpha-hemolysin (alpha-HL) ion channel, and through a Monte Carlo (MC)
      model of polymer capture rate with a cylindrical nanopore under an applied
      voltage. Experimental and model results are extrapolated to predict the capture
      rate of synthetic pores operating at higher voltages than presently achievable
      with protein pores.

PMID- 12210163
TI  - Concentration gradient used in double-stranded DNA separation by capillary
      electrophoresis.
AB  - Effects of concentration gradient on double-stranded DNA (dsDNA) separation by
      capillary electrophoresis are presented. By using a concentration gradient in the
      range between 0.8% and 3.2% for poly(N,N-dimethylacrylamide) (PDMA), the presence
      of a mesh-size gradient in the capillary could enhance the separation of larger
      size DNA fragments, better than that based on a single uniform concentration over
      the same capillary length. A decrease in the column length could make the
      gradient effect more obvious. An optimal capillary length could be achieved by
      using a judicious combination of the concentration gradient and the concentration
      range, yielding a maximum resolution for the system. The standard deviation of
      the migration time measured for each DNA fragment was less than 5% in ten
      continuous runs, suggesting that the gradient formed inside the column was quite
      stable.

PMID- 12210164
TI  - Cyclic capillary electrophoresis.
AB  - A strategy is described here for increasing both the resolution and the
      flexibility of capillary electrophoresis performed in a sieving medium of
      ungelled polymer. This strategy is based on analysis and, sometimes, re-analysis
      that is done in several stages of constant-field electrophoresis. Enhancement
      stages are between the analysis-stages. An enhancement-stage (i) increases the
      separation between peaks, while (ii) moving DNA molecules in the reverse
      direction. An enhancement-stage is based on an electrophoretic ratchet generated
      by a pulsed electrical field that can be zero-integrated. The ratchet-generating
      pulses are longer than the field pulses that have previously been used to improve
      the resolution of DNA molecules. No limit has been found to the resolution
      enhancement achievable. Apparently, diffusion-induced peak broadening is
      inhibited and, in some cases, may be reversed by the ratchet. The enhancement
      stages are critically dependent on the electrical field-dependence of a plot of
      electrophoretic mobility as a function of DNA length. To generate the pulsed
      electrical field, a computer-controlled system with a time resolution of 30
      microseconds has been developed. Programming is flexible enough to embed other
      pulses within ratchet-generating pulses. These other pulses can be either the
      previously used, shorter field-inversion pulses or high-frequency periodic
      oscillations previously found to sharpen peaks.

PMID- 12210165
TI  - DNA separation at a liquid-solid interface.
AB  - We demonstrate that it is possible to separate a broad band of DNA on a solid
      substrate without topological obstacles. The mobility was found to scale with
      molecular size (N) as N(-0.25), while the resolution scaled as N(0.75) indicating
      that diffusivity on this substrate was minimal. By varying the buffer
      concentration we were able to show that the mobility for a given chain length
      scaled with the persistent length (p) as p(1/2). This could be shown to be
      related to the Gaussian conformation of the chains adsorbed on the surface. A two
      dimensional corrugated surface of nonporous silica beads was produced using a
      self-assembling process at the air/water interface. Even though the surface
      corrugations were comparable to persistence length we show that they do not
      affect the mobility, indicating that surface friction rather than topological
      constraints are the predominant mechanism of separation on a surface.

PMID- 12210166
TI  - Nonlinear electrophoresis of point-like particles--is it possible?
AB  - A new universal method for the generation of nonlinear electrophoretic mobility
      of a packet of any particles is suggested. The method is based on the
      investigation of particle packet dynamics under the influence of an external
      force. The system under consideration is a homogeneous and isotropic medium with
      traps for these particles. Packet dynamics is described by a linear diffusion
      equation. The measured packet parameters are the position and the velocity of a
      packet maximum. It is shown that these parameters are nonlinear in the external
      field under definite limitations on the trap properties. This statement is proved
      both theoretically and experimentally for the simple model of diffusive
      substrate, the so-called comb structure. The prospects of designing new
      supporting substrates (microfluidic systems) with a nonlinear response are
      discussed.

PMID- 12210167
TI  - Investigation of the possibility of geometrical electrophoresis.
AB  - We investigate the possibility of geometrical electrophoresis, which is based on
      nanofabrication techniques. (GEE) utilizes geometrical effects during
      electrophoresis, which are generated by physical interactions between walls and a
      macromolecule confined in spaces smaller than the Flory radius. When a polymer is
      injected into a small space, confinement energy is usually required. However, the
      confinement energy form depends on the geometry of the space. In the case of
      electrophoresis, the electric field itself changes depending on the geometry.
      Using a nanofabricated quartz chip with a curved channel, we investigated
      electrophoretic behavior of high molecular weight DNA based on the curvature
      effect.

PMID- 12210168
TI  - Passive electrophoresis in microchannels using liquid junction potentials.
AB  - The formation of the liquid junction potential (LJP) is a well-studied phenomenon
      that occurs in the presence of ionic concentration gradients. Although the LJP
      has been well characterized, its impact has generally been overlooked in
      microfluidic applications. The characteristics of flow in microfluidic channels
      cause this phenomenon to be particularly important, both as a source of deviation
      from anticipated results and as a tool capable of being harnessed to perform
      useful tasks. It is demonstrated that LJPs formed in microchannels can induce
      appreciable electrophoretic transport of charged species without the use of
      electrodes or an external power supply. This process is demonstrated in an H
      filter (an H-shaped microfluidic channel used to bring two fluids into contact
      allowing extraction of diffusing species from one stream to another) by
      generating junction potentials between two flowing streams containing different
      concentrations of strong electrolytes and observing the mass transport of the
      charged dye fluorescein between those streams. It is shown that the LJP can be
      controlled to either accelerate or decelerate mass transport across a fluid
      interface in the absence of an interposed membrane. A preliminary mathematical
      description of the phenomena is offered to support the hypothesis that the
      observed mass transport is a result of the LJP. Possible practical microfluidic
      applications of electrophoretic transport without electrodes are discussed.

PMID- 12210169
TI  - Velocity-independent microfluidic flow cytometry.
AB  - Pressure-driven flow in microfluidic channels is characterized by a distribution
      of velocities. This distribution makes it difficult to implement conventional
      flow cytometry data analysis. We have demonstrated a method to measure velocity
      as an independent parameter when performing microfluidic flow cytometry. This
      method allows velocity-independent analysis of particles such as beads or cells,
      and allows flow cytometry analysis of extended objects, such as long DNA
      molecules. It allows accurate flow cytometry in transient and nonuniform flows.
      This general measurement method could be used in the future to measure the
      velocity of particles in a variety of existing microfluidic devices without the
      need for changes in their design.

PMID- 12210170
TI  - Trapping of DNA by dielectrophoresis.
AB  - Under suitable conditions, a DNA molecule in solution will develop a strong
      electric dipole moment. This induced dipole allows the molecule to be manipulated
      with field gradients, in a phenomenon known as dielectrophoresis (DEP). Pure
      dielectrophoretic motion of DNA requires alternate current (AC) electric fields
      to suppress the electrophoretic effect of the molecules net charge. In this
      paper, we present two methods for measuring the efficiency of DEP for trapping
      DNA molecules as well as a set of quantitative measurements of the effects of
      strand length, buffer composition, and frequency of the applied electric field. A
      simple configuration of electrodes in combination with a microfluidic flow
      chamber is shown to increase the concentration of DNA in solution by at least 60
      fold. These results should prove useful in designing practical microfluidic
      devices employing this phenomenon either for separation or concentration of DNA.

PMID- 12210171
TI  - Optimization of background electrolytes for capillary electrophoresis: II.
      Computer simulation and comparison with experiments.
AB  - A mathematical and computational model described in the previous paper (Gas, B.,
      Coufal, P., Jaros, M., Muzikar, J., Jelinek, L., J. Chromatogr. A 2001, 905, 269
      279) is adapted, algorithmized, and a computer program PeakMaster having a status
      of freeware (http://natur.cuni.cz/ approximately gas) is introduced. The model
      enables optimization of background electrolyte (BGE) systems for capillary zone
      electrophoresis. The model allows putting to use uni- or di- or trivalent
      electrolytes and allows also for modeling highly acidic or alkaline BGEs. It
      takes into account the dependence of ionic mobilities and dissociation of weak
      electrolytes on the ionic strength. The model calculates the effective mobility
      of analytes and predicts parameters of the system that are experimentally
      available, such as the transfer ratio, which is a measure of the sensitivity in
      the indirect UV detection or the molar conductivity detection response, which
      expresses the sensitivity of the conductivity detection. Further, the model
      enables evaluation of a tendency of the analyte to undergo electromigration
      dispersion or peak broadening. The suitability of the model is verified by
      comparison of the predicted results with experiments, even under conditions that
      are far from ideal (under extreme pH and a high ionic strength).

PMID- 12210172
TI  - Modeling the gel electrophoresis of short duplex DNA by Brownian dynamics: cubic
      gel lattice with direct interaction.
AB  - The technique of Brownian dynamics is used to model the electrophoretic mobility
      of spherical and rod-like particles in a three-dimensional cubic gel lattice. In
      addition to excluded volume interactions between the migrating particle and the
      gel, direct interactions are also included. The methodology is first applied to
      spherical particles in the absence of direct interactions and the resulting
      mobilities are shown to agree with independent studies. The methodology is then
      applied to rod-like models of short duplex DNA fragments 10-50 base pairs in
      length. In the absence of direct interactions between gel and DNA, calculated
      mobilities show a much weaker dependence on gel concentration than observed in
      experiments of DNA in Tris-acetate buffer and polyacrylamide gels. When an
      attractive interaction between gel and DNA of approximately -0.3 k(B)T per base
      pair at contact is included, good agreement between calculated and experimental
      mobilities is achieved.

PMID- 12210173
TI  - Modeling the dynamics of DNA electrophoresis on a flat surface.
AB  - We use molecular dynamics simulations to study the mechanism by which a flat,
      homogeneous surface can serve as an electrophoretic separation medium for DNA. We
      find that the mobility of DNA on the surface is a function of the conformation of
      the adsorbed DNA molecule, and that this mobility is controlled by the attraction
      between the DNA and the surface. Our results will provide guidelines for the
      fabrication of surfaces that can be used to separate DNA in a wide size range.

PMID- 12210174
TI  - Modeling of polynucleotide translocation through protein pores and nanotubes.
AB  - In an effort to understand recent experiments, we have performed Brownian
      dynamics simulations of polymer translocation through nanometer-scale protein
      pores under the influence of an external applied electric field. Multiple peaks
      in the translocation time distribution are observed in agreement with
      experiments. Under the same conditions, but replacing the protein pore with a
      rigid cylindrical tube of comparable size, only a single peak is observed in the
      translocation time distribution. These results directly show that the geometry of
      the protein pores is mainly responsible for multiple peaks observed in
      experiments. In the case of alpha-hemolysin channel, we find the vestibule, by
      confining many conformations of the translocating polymer, to be responsible for
      the second peak with longer translocation time.

PMID- 12210175
TI  - The propagator (retarded Green function) formalism as a new calculation method to
      predict the time evolution of bands in capillary electrophoresis and
      microchannels.
AB  - Capillary electrophoresis (CE) and microchannel (MC) techniques are important
      tools in chemical and biological sciences, mainly in the study of genomes,
      transcriptomes, proteomes, metabolomes, and organic as well as inorganic ions.
      The speed of DNA sequencing increased significantly during the last decade with
      the use of capillary electrophoresis (CE). The time evolution of the bands'
      spatial profile inside capillaries and channels is of paramount importance, since
      the main goal of these techniques is to maximize resolution (the ratio between
      the spacing of the peaks and their mean standard deviations). In the present
      work, the propagator (retarded Green function) formalism is applied to solve a
      few problems which are typical for CE and MC. We also apply this mathematical
      method to the problem of velocity gradients along the capillary, i.e., the time
      evolution of the bands is analyzed when they enter regions where they migrate
      with different velocities.

PMID- 12210176
TI  - DNA electrophoresis in agarose gels: effects of field and gel concentration on
      the exponential dependence of reciprocal mobility on DNA length.
AB  - Electrophoretic mobilities of DNA molecules ranging in length from 200 to 48 502
      base pairs (bp) were measured in agarose gels with concentrations T = 0.5% to
      1.3% at electric fields from E = 0.71 to 5.0 V/cm. This broad data set determines
      a range of conditions over which the new interpolation equation nu(L) =
      (beta+alpha(1+exp(-L/gamma))(-1) can be used to relate mobility to length with
      high accuracy. Mobility data were fit with chi(2) > 0.999 for all gel
      concentrations and fields ranging from 2.5 to 5 V/cm, and for lower fields at low
      gel concentrations. Analyses using so-called reptation plots (Rousseau, J.,
      Drouin, G., Slater, G. W., Phys. Rev. Lett. 1997, 79, 1945-1948) indicate that
      this simple exponential relation is obeyed well when there is a smooth transition
      from the Ogston sieving regime to the reptation regime with increasing DNA
      length. Deviations from this equation occur when DNA migration is hindered,
      apparently by entropic-trapping, which is favored at low fields and high gel
      concentrations in the ranges examined.

PMID- 12210177
TI  - A general approach to the analysis of errors and failure modes in the base
      calling function in automated fluorescent DNA sequencing.
AB  - We describe the analysis of errors and failure modes in the base-calling function
      in automated DNA sequencing, on instruments in which fluorescently-labeled Sanger
      dideoxy-sequencing ladders are detected via their times of migration past a fixed
      detector. A general approach entails the joint use of: (i) well-defined control
      samples such as M13mp18, and (ii) mathematical simulation of sequencing
      electropherograms, with the deliberate introduction of different types of
      distortion and noise. An algorithm, the electrophoretic trace simulator (ETS), is
      used to calculate electrophoresis traces corresponding to the output data stream
      of an automated fluorescent DNA sequencer. The ETS accepts a user-defined
      sequence of nucleotide bases (A, C, G, T) as input, and employs user-adjustable
      functions to compute the following critical parameters of an electropherogram:
      peak intensity, peak spacing, peak shape as a function of base number;
      background, noise, and spectral cross-talk correction (for a sequencer using
      multiple dyes). We use a combination of M13mp18 controls and simulated
      electropherograms to analyze two problems of considerable practical importance:
      (i) variation in electrophoretic migration rates between different lanes of a
      gel, and (ii) variation in signal intensity due to user-dependent loading
      artifacts. The issue of base-calling errors and failure modes, for
      electropherograms that contain noise and distortion, is addressed.

PMID- 12210178
TI  - Design and optimization of on-chip capillary electrophoresis.
AB  - We present a systematic, experimentally validated method of designing
      electrokinetic injections for on-chip capillary electrophoresis applications.
      This method can be used to predict point-wise and charge-coupled device (CCD)
      imaged electropherograms using estimates of species mobilities, diffusivities and
      initial sample plug parameters. A simple Taylor dispersion model is used to
      characterize electrophoretic separations in terms of resolution and signal-to
      noise ratio (SNR). Detection convolutions using Gaussian and Boxcar detector
      response functions are used to relate optimal conditions for resolution and
      signal as a function of relevant system parameters including electroosmotic
      mobility, sample injection length, detector length scale, and the length-to
      detector. Analytical solutions show a tradeoff between signal-to-noise ratio and
      resolution with respect to dimensionless injection width and length to the
      detector. In contrast, there is no tradeoff with respect to the Peclet number as
      increases in Peclet number favor both SNR and separation solution (R). We
      validate our model with quantitative epifluorescence visualizations of
      electrophoretic separation experiments in a simple cross channel microchip. For
      the pure advection regime of dispersion, we use numerical simulations of the
      transient convective diffusion processes associated with electrokinetics together
      with an optimization algorithm to design a voltage control scheme which produces
      an injection plug that has minimal advective dispersion. We also validate this
      optimal injection scheme using fluorescence visualizations. These validations
      show that optimized voltage scheme produces injections with a standard deviation
      less than one-fifth of the width of the microchannel.

PMID- 12210179
TI  - The effect of obstacle conductivity and electric field on effective mobility and
      dispersion in electrophoretic transport: a volume averaging approach.
AB  - The method of volume averaging has been used to determine the effective
      electrophoretic mobility and dispersion coefficients for molecular transport of
      point-like solutes in a two-phase porous medium where the electrical conductivity
      and the diffusion and mobility coefficients may vary in both phases. The formal
      theory, derived in previous work, is numerically evaluated for cases where the
      obstacle phase has a large or small conductivity relative to the fluid phase and
      where the diffusion coefficient of the solute in the obstacle phase can be large
      or small relative to that in the fluid phase. In agreement with previous Monte
      Carlo methods, the effective electrophoretic mobility is not a function of media
      conductivity or electric field when the obstacles are impermeable to solute
      transport or have small diffusion solute diffusion coefficients. However, the
      dispersion coefficient is a strong function of electric field and varies with
      obstacle conductivity when diffusive transport is small in the obstacles relative
      to the fluid. In contrast, the effective electrophoretic mobility is a function
      of electric field when conductivity of the obstacles is much larger than the
      fluid and when the obstacles are very permeable to solute but have low electrical
      conductivity.

PMID- 12210180
TI  - Simultaneous measurements of the electrophoretic mobility, diffusion coefficient
      and orientation of dsDNA during electrophoresis in polymer solutions.
AB  - We determined simultaneously the electrophoretic mobility, diffusion coefficient
      D and molecular orientation during electrophoresis of dsDNAs in polymer solutions
      ranging from the dilute to the semidilute regime. We established, for the first
      time, master scaling laws for the diffusion coefficient showing a universal
      behavior. A model found in the literature designed for the dilute regime allows,
      surprisingly, to describe the mobility data over the whole range of
      concentrations studied and at the same time the biased reptation with
      fluctuations (BRF) failed for the semidilute regime, even when constraint release
      of the network was taken into account. These quantitative determinations of D are
      of practical interest to evaluate band broadening during capillary
      electrophoresis and provide data for stimulating investigation of the physics of
      DNA electrophoretic motion.

PMID- 12210181
TI  - Critical factors for high-performance physically adsorbed (dynamic) polymeric
      wall coatings for capillary electrophoresis of DNA.
AB  - Physically adsorbed (dynamic) polymeric wall coatings for microchannel
      electrophoresis have distinct advantages over covalently linked coatings. In
      order to determine the critical factors that control the formation of dynamic
      wall coatings, we have created a set of model polymers and copolymers based on
      N,N-dimethylacrylamide (DMA) and N,N-diethylacrylamide (DEA), and studied their
      adsorption behavior from aqueous solution as well as their performance for
      microchannel electrophoresis of DNA. This study is revealing in terms of the
      polymer properties that help create an "ideal" wall coating. Our measurements
      indicate that the chemical nature of the coating polymer strongly impacts its
      electroosmotic flow (EOF) suppression capabilities. Additionally, we find that a
      critical polymer chain length is required for polymers of this type to perform
      effectively as microchannel wall coatings. The effective mobilities of double
      stranded (dsDNA) fragments within dynamically coated capillaries were determined
      in order to correlate polymer hydrophobicity with separation performance. Even
      for dsDNA, which is not expected to be a strongly adsorbing analyte, wall coating
      hydrophobicity has a deleterious influence on separation performance.

PMID- 12210182
TI  - Microdevice-based measurements of diffusion and dispersion in cross-linked and
      linear polyacrylamide DNA sequencing gels.
AB  - We use microfabricated gel electrophoresis devices incorporating integrated on
      chip electrodes, heaters, and temperature sensors to measure diffusion and
      dispersion of single-stranded DNA fragments in cross-linked and uncross-linked
      polyacrylamide gels. The microdevice format allows a complete set of diffusion
      and dispersion data to be collected in approximately one hour. These results are
      compared with corresponding data obtained in a macroscale DNA sequencer, and the
      effects of gel composition and initiation chemistry are explored. Although the
      diffusion and dispersion data exhibit similar qualitative trends both on chip and
      on the macroscale, the magnitudes of the coefficients measured in the microdevice
      are somewhat higher. This discrepancy is likely due to altered polymerization
      kinetics arising as a consequence of using a UV-initiated polymerization
      chemistry to cast the on-chip gels as opposed to the standard chemical
      polymerization employed on the macroscale. We also find that reductions in the
      magnitudes of diffusion and dispersion coefficients are achieved at higher
      polymer concentrations and at operating temperatures in the vicinity of 50
      degrees C. Finally, we find that cross-linked polyacrylamide gels yield
      significantly lower diffusion and dispersion coefficients than linear
      polyacrylamide. These findings can be used to identify rational strategies to
      improve separation performance in both micro- and macroscale gel electrophoresis
      systems.

PMID- 12210183
TI  - Size-based separation of synthetic polyelectrolytes in entangled polymer solution
      capillary electrophoresis: the effect of binary mixtures of separating polymers
      differing in molecular mass.
AB  - The influence on the electrophoretic behavior of polystyrenesulfonates of the
      percentage of high-molecular-mass chains in an entangled poly(ethylene oxide)
      solution having a bimodal molecular mass distribution has been investigated and
      compared with the results obtained for similar solutions of unimodal molecular
      mass distribution. The comparisons between the different separating polymer
      solutions were made at a constant total mass concentration, so as to keep
      constant the mesh size and to highlight the sole effect of the network dynamics.
      The use of binary polymer mixtures of two different molecular masses but of same
      nature can be a convenient alternative to modulate the dynamics of the network
      and the viscosity of the separating medium. A 20-30% content of high-molecular
      mass chains in an entangled poly(ethylene oxide) solution having a binary
      molecular mass distribution appears to be a good compromise for a moderate
      viscosity and a good separation selectivity in comparison with a solution
      containing only chains of high molecular mass at the same concentration.

PMID- 12210184
TI  - Determining the electrophoretic mobility and translational diffusion coefficients
      of DNA molecules in free solution.
AB  - The free solution mobility of DNA molecules of different molecular weights, the
      sequence dependence of the mobility, and the diffusion coefficients of small
      single- and double-stranded DNA (ss- and dsDNA) molecules can be measured
      accurately by capillary zone electrophoresis, using coated capillaries to
      minimize the electroosmotic flow (EOF) of the solvent. Very small differences in
      mobility between various analytes can be quantified if a mobility marker is used
      to correct for small differences in EOF between successive experiments. Using
      mobility markers, the molecular weight at which the free solution mobility of
      dsDNA becomes independent of molecular weight is found to be approximately 170 bp
      in 40 mM Tris-acetate-EDTA buffer. A DNA fragment containing 170 bp has a contour
      length of approximately 58 nm, close to the persistence length of DNA under these
      buffer conditions. Hence, the approach of the free solution mobility of DNA to a
      plateau value may be associated with the transition from a rod-like to a coil
      like conformation in solution. Markers have also been used to determine that the
      free solution mobilities of ss- and dsDNA oligomers are sequence-dependent.
      Double-stranded 20-bp oligomers containing runs of three or more adenine residues
      in a row (A-tracts) migrate somewhat more slowly than 20-mers without A-tracts,
      suggesting that somewhat larger numbers of counterions are condensed in the ion
      atmospheres of A-tract DNAs, decreasing their net effective charge. Single
      stranded 20-mers with symmetric sequences migrate approximately 1% faster than
      their double-stranded counterparts, and faster than single-stranded 20-mers
      containing A(5)- or T(5)-tracts. Interestingly, the average mobility of two
      complementary single-stranded 20-mers is equal to the mobility of the double
      stranded oligomer formed upon annealing. Finally, the stopped migration method
      has been used to measure the diffusion coefficients of single- and double
      stranded oligomers. The diffusion coefficients of ssDNA oligomers containing 20
      nucleotides are approximately 50% larger than those of double-stranded DNA
      oligomers of the same size, reflecting the greater flexibility of ssDNA
      molecules. The methods used to carry out these experiments are also described in
      detail.

PMID- 12210185
TI  - A family of novel DNA sequencing instruments based on single-photon detection.
AB  - We have developed a family of high-performance capillary DNA sequencing
      instruments based on a novel multicolor fluorescent detection technology. This
      technology is based on two technical innovations: the multilaser excitation of
      fluorescence of labeled DNA fragments and the "color-blind" single-photon
      detection of modulated fluorescence. Our machines employ modern digital and
      broadband techniques that are essential for achieving superior instrument
      performance. We discuss the design and testing results for several versions of
      the automated single lane DNA sequencers, as well as our approach to scaling up
      to multilane instruments.

PMID- 12210188
TI  - Electrophoretic mobility of human erythrocytes in the presence of poly(styrene
      sulfonate).
AB  - The adsorption and depletion of the anionic polymer poly(styrene sulfonate) (PSS)
      on fresh human red blood cells (RBC) were investigated by measuring RBC
      electrophoretic mobility as a function of polymer molecular mass (48-2610 kDa),
      ionic strength (15 and 150 mM NaCl) and polymer concentration (<or= 1.5 g/dL). A
      subset of studies was carried out using fixed and PSS-coated cells. Our results
      indicate a marked increase of mobility with molecular mass and polymer
      concentration. Adsorption of PSS onto fresh RBC was weak, with normal mobility
      restored following washing cells in PSS-free buffer. Calculated zeta potentials
      based upon mobility and medium viscosity rose up to 618 mV for 2610 kDa PSS
      compared to 13 mV for control cells, thus suggesting significant polymer
      depletion at the cell surface; fixed and PSS-coated RBC were insensitive to
      medium viscosity, also validating this depletion layer hypothesis. Calculated
      values of increased RBC surface charge were used to estimate polymer adsorption
      per cell; these estimates indicated linear adsorption isotherms and binding
      levels consistent with studies employing neutral polymers. In overview, our
      results suggest the usefulness of microelectrophoresis methods for studies of RBC
      interactions with charged polymers or proteins, and the value of this approach
      for future studies using proteins known to affect RBC-RBC interactions.

PMID- 12210189
TI  - Activity staining of plasma amine oxidase after polyacrylamide gel
      electrophoresis and its application to natural inhibitor screening.
AB  - Plasma amine oxidase (plasma AO, EC 1.4.3.6) is a copper-containing AO which
      converts benzylamine (BZ) to benzaldehyde, generating hydrogen peroxide and
      ammonia. The peroxidase was used as an ancillary enzyme to couple hydrogen
      peroxide to 3-amino-9-ethylcarbazole (AEC) to achieve plasma AO activity after
      electrophoresis on native polyacrylamide gels. It was confirmed that plasma AO is
      inhibited by semicarbazide but neither by clorgyline nor by deprenyl. We also
      used plasma AO activity staining for the screening of natural inhibitors. This
      fast and sensitive method can be used in the process of plasma AO purification,
      characterization, and inhibitor screening.

PMID- 12210190
TI  - An improved western blotting technique effectively reduces background.
AB  - We have developed a simple method to dramatically improve Western blotting by use
      of water washing as well as altered buffer conditions. Our improved protocol
      reduces the cost and labor of Western blotting by shortening the washing time and
      uses less buffer and other reagents. This procedure does not significantly change
      existing protocols of Western blotting analysis; it simply contains a few
      modifications to the washing step and buffer conditions. Our improved technique
      may therefore have broad applications in various experimental conditions.

PMID- 12210191
TI  - Mutation at minisatellite locus DYF155S1: allele length mutation rate is affected
      by age of progenitor.
AB  - A father/son material consisting of 1071 pairs was screened for de novo allele
      length mutation in locus DYF155S1. Six hundred of these pairs were also analyzed
      in locus DYF155S1 to detect de novo mutations in the minisatellite variant repeat
      (MVR)-code not resulting in a length change ("boundary switch" mutations). A
      modified MVR-polymerase chain reaction (PCR) method was used for this purpose.
      Twenty-seven de novo allele length mutations and eight "boundary switch"
      mutations were detected indicating mutation frequencies of approximately 2.5% and
      1.3%, respectively. The combined mutation rate for MVR-code mutation is
      approximately 3.8%. There is a significant increase in mutation rate with
      paternal age (p = 0.049) in allele length mutations. In the present material, the
      mutation rate in the oldest age group is three times that of the youngest age
      group. A similar age relationship is not observed in "boundary switch" mutations.
      A comparison between progenitors and the other fathers in the material revealed
      no obvious association between mutation rate and allele length or modular
      structure (variation in repeat sequence). More than 75% of the length mutations
      involved the gain or loss of one repeat only. This finding as well as the
      observed paternal age influence on mutation rate, suggests replication slippage
      to be the major mutation mechanism in length mutations. However, in one
      particular case, an allele length mutant revealed rearrangements with direct
      duplication of repeats at distant sites within the repeat array, and with both
      loss and gain of repeats. Such complex structural changes could indicate that
      some of the mutants might arise from sister chromatide exchange. The mutation
      rate of "boundary switch" mutations is by far higher than would be expected if
      these mutations are two independent one-step allele length mutations. A different
      age distribution of "boundary switch" mutations than of allele length mutations
      also argue against such a hypothesis. Together this could indicate that "boundary
      switches" are products of another mutation mechanism than the one-step allele
      length mutations.

PMID- 12210192
TI  - Monitoring of single nicks in duplex DNA by gel electrophoretic mobility-shift
      assay.
AB  - We demonstrate that the gel electrophoretic mobility-shift assay (EMSA) can be
      used for site-selective and quantitative monitoring of nicks in linear double
      stranded DNA (dsDNA) thus allowing to expediently follow the nicking activity of
      enzymes or other agents targeted to a designated dsDNA site. At elevated
      temperature and/or in the presence of urea, DNA fragments carrying a single nick
      produced by the nicking enzyme N.BstNBI exhibit a well-detectable gel retardation
      effect. On the basis of permutation analysis, the decreased electrophoretic
      mobility of nicked dsDNA fragments is attributed to a bend (or hinge) in the DNA
      double helix sequence-specifically generated by a nick. Since nick-induced DNA
      bending depends on interaction between base pairs adjacent to a nick, the change
      in mobility is different for nicked DNA sites with different sequences.
      Therefore, EMSA monitoring of differential mobility change caused by nicks within
      various DNA sequences could be useful for studying the differential base stacking
      and nearest-neighbor energetics.

PMID- 12210193
TI  - The impact of a plug of salts on the analysis of large volumes of dsDNA by
      capillary electrophoresis.
AB  - A partially filling technique for the analysis of DNA markers and polymerase
      chain reaction (PCR) products by capillary electrophoresis in the presence of
      electroosmotic flow using polymer solutions is presented. Either after or prior
      to the sample injection, a plug of salts at high pH was hydrodynamically
      injected. During the separation, poly(ethylene oxide) (PEO) solution entered the
      capillary. We have found that the position, length, and composition of the plugs
      affect the sensitivity, resolution, and speed on the analysis of PhiX-174/HaeIII
      DNA restriction fragments or a DNA mixture (pBR 322/HaeIII digest, pBR 328/BglI
      digest and pBR 328/HinfI digest) with different degrees. Through careful
      evaluation of the impact of anions and cations on the analysis of DNA, we have
      suggested that the optimal condition is applying a plug consisting of 32 mM NaCl
      and 0.01 M NaOH at 30 cm height for 60 s after sample injection. In the presence
      of such a plug, PEO adsorption reduces, and thus the separation is faster, as
      well as the sensitivity improves. Using this condition, the analysis of a DNA
      mixture (injected at 30 cm for 360 s) containing ten different PCR products
      amplified after 17 cycles was complete in 25 min. About a 2000-fold improvement
      in the sensitivity was achieved when compared to that by a conventional method
      (10 s injection) without applying a plug.

PMID- 12210194
TI  - Stacking by electroinjection with discontinuous buffers in capillary zone
      electrophoresis.
AB  - The work presented here demonstrates that electroinjection can be performed using
      discontinuous buffers, which can result in better stacking than that obtained by
      hydrodynamic injection. The sample can be concentrated at the tip of the
      capillary leaving practically the whole capillary for sample separation. This
      results in several advantages, such as better sample concentration, higher plate
      number and shorter time of stacking. However, sample introduction by
      electromigration is suited for samples free or low in salt content. Samples,
      which are high in salt content, are better introduced by the hydrodynamic
      injection for stacking by the discontinuous buffers. Different simple methods to
      introduce the discontinuity in the buffer for electroinjection are discussed.

PMID- 12210195
TI  - Application of capillary electrophoresis with field-amplified sample injection
      for the detection of new adrenoreceptor antagonist enantiomers in plasma in the
      low ng/mL concentration range.
AB  - Throughout the separation of chiral basic drugs by capillary electrophoresis (CE)
      with neutral hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as chiral selector, the
      sensitivity of detection has been improved by using field-amplified sample
      injection (FASI). In the present work, this on-line stacking method has been used
      to detect low ng/mL levels of cationic enantiomers of a new adrenoreceptor
      antagonist in plasma. A systematic study of the parameters affecting on-line
      concentration of these enantiomers (nature of the preinjection plug, composition
      of sample solvent, injection times of water and sample plugs) has been performed
      enabling the detection sensitivity of antagonist enantiomers to be improved by
      180 times compared with usual hydrodynamic injection. The quantification of each
      adrenoreceptor antagonist enantiomer in plasma samples was then performed in the
      2-100 ng/mL (or 8-400 nM) concentration range after a solid-phase extraction
      step. Using this FASI-CE-UV procedure, the limit of quantification (LOQ) for each
      enantiomer was in the low ng/mL concentration range (3 ng/mL or 10 nM).

PMID- 12210196
TI  - Solute-solvent interactions in micellar electrokinetic chromatography: V. Factors
      that produce peak splitting.
AB  - The experimental conditions that produce analyte peak splitting in micellar
      electrokinetic capillary chromatography (MEKC) have been systematically
      investigated. The system studied was a neutral phosphate buffer and sodium
      dodecyl sulfate (SDS) micelles as pseudostationary phase. A number of analytes
      showing a wide variety of hydrophobicity values and several organic solvents as
      sample diluents have been tested. Peak splitting phenomena are mainly due to the
      presence of organic solvent in the sample solution. They increase with the
      hydrophobicity of the analyte and decrease with the increase of the surfactant
      concentration. When hydrophobic compounds are analyzed the suggested ways to
      avoid split peaks are: (i) the use of 1-propanol or 1-butanol as sample diluent
      instead of methanol or acetonitrile or (ii) the use of high concentration of
      surfactant in the separating solution when the analyte must be dissolved in pure
      methanol or acetonitrile.

PMID- 12210197
TI  - Characteristics of electroosmotic flow and migration of neutral solutes under
      stepwise gradient elution of capillary electrochromatography.
AB  - A theoretical study on the velocity of electroosmotic flow (EOF) and the
      retention times of neutral solutes under multiple-step gradient of capillary
      electrochromatography (CEC) was carried out, focusing on that with three kinds of
      mobile phases. Through the model computations, the detaining time of the second
      kind of mobile phase in the column was proved to play an important role in
      affecting EOF. The variation speed of EOF was shown to be determined by the
      differences among dead times in different steps. In addition, the prediction of
      the retention times of 13 aromatic compounds under gradient mode was performed
      with the deduced equations. A relative error below 3.3% between the calculated
      and experimental values was obtained, which demonstrated the rationality of the
      theoretical deduction. Our study could not only improve the comprehension of
      stepwise gradient elution, but also be of significance for the further
      optimization of separation conditions in the analysis of complex samples.

PMID- 12210198
TI  - Development and optimization of an analytical method for the determination of UV
      filters in suntan lotions based on microemulsion electrokinetic chromatography.
AB  - Microemulsion electrokinetic chromatography (MEEKC) has been applied to the
      separation of some UV filters (Eusolex 4360, Eusolex 6300, Eusolex OCR, Eusolex
      2292, Eusolex 6007, Eusolex 9020, Eusolex HMS, Eusolex OS, and Eusolex 232)
      commonly found in suntan lotions. The composition of the microemulsion employed
      was optimized with respect to the best possible separation of the selected
      analytes using artificial neural networks (ANNs). Two parameters namely the
      composition of the mixed surfactant system comprising the anionic sodium dodecyl
      sulfate (SDS) and neutral Brij 35 and the amount of organic modifier (2-propanol)
      present in the aqueous phase of the microemulsion were modeled. Using an
      optimized MEEKC buffer consisting of 2.25 g SDS, 0.75 g Brij 35, 6.6 g 1-butanol,
      0.8 g n-octane, 17.5 g 2-propanol, and 72.1 g of 10 mM borate buffer (pH 9.2),
      eight target analytes could be separated in under 25 min employing a diode-array
      detector to segregate the overlapping signals obtained for Eusolex 9020 and
      Eusolex HMS. Detection limits from 0.8 to 6.0 nug/mL were obtained and the
      calibration plots were linear over at least one order of magnitude. The optimized
      method could be applied to the determination of Eusolex 6300 and Eusolex 9020 in
      a commercial suntan lotion.

PMID- 12210199
TI  - Separation of organic and inorganic arsenic species by capillary electrophoresis
      using direct spectrophotometric detection.
AB  - Capillary electrophoresis (CE) with UV detection was used for the determination
      of arsenite, arsenate, monomethylarsonic acid, dimethylarsinic acid, p
      aminophenylarsonic acid, 4-hydroxy-3-nitrobenzenearsonic acid, 4
      nitrophenylarsonic acid, phenylarsonic acid, and phenylarsine oxide. The
      electrophoretic mobilities of these anionic species were determined in a 20 mM
      phosphate buffer in a pH range from 4 to 11, which established pH 10 as the
      optimum for the separation. The target analytes were then separated in a fused
      silica capillary using 20 mM NaHCO(3)-Na(2)CO(3) buffer, pH 10, as electrolyte
      and detected at 192 nm. Both normal- and reversed electroosmotic flow (EOF)
      separation modes were investigated and in the latter case,
      poly(diallydimethylammonium chloride) (PDDAC), was used for dynamic coating of
      the capillary and to provide a stable and reproducible reversed EOF (relative
      standard deviation RSD, 0.39%). The influence of electrolyte pH and composition,
      applied voltage, as well as EOF reversal protocols upon the method performance
      criteria were investigated. The optimised method provided limits of detection for
      the target analytes of 1.62, 6.22, 1.45, 1.83, 0.34, 0.40, 0.40, 0.18, and 0.30
      mg/L As, respectively. Linearity was obtained in the range of 0.5-40 mg/L As (for
      aryl compounds) and from 5-100 mg/L As (for the remaining analytes).
      Reproducibility of peak areas was in the range of 0.8-5.5% RSD. The method was
      applied to the determination of four aryl arsenic compounds used as additives in
      animal feed. Analytes were extracted with 40 mM hydrochloric acid - acetonitrile
      4:1 v/v, and then cleaned up by passing through a C(18) solid-phase extraction
      cartridge before analysis by CE with detection at 200 nm. Recoveries for the four
      analytes were in the range of 78.8-108.3%.

PMID- 12210200
TI  - Capillary electrophoretic determination of thiosulfate, sulfide and sulfite using
      in-capillary derivatization with iodine.
AB  - A new capillary electrophoresis (CE) method was developed for the rapid, simple
      and selective determination of thiosulfate, sulfide and sulfite species. The
      proposed method is based on the in-capillary derivatization of separated sulfur
      anions by mixing their zones with the iodine zone during the electrophoretic
      migration and direct UV detection of iodide formed. The optimal conditions for
      the separation and derivatization reaction were established by varying
      electrolyte pH, electrolyte counter-ion, concentration of iodine, and applied
      voltage. The optimized separations were carried out in 20 mmol/L Tris-chloride
      electrolyte (pH 8.5) using direct UV detection at 214 nm. All three sulfur
      species were well resolved in less than 4 min. The method gives repeatability
      comparable or even better than this obtained for sulfur anions using standard CE
      technique. The proposed CE system was applied to the monitoring of sulfur anions
      in spent fixing solutions during the electrolytic oxidation.

PMID- 12210201
TI  - Performance of an ultraviolet light-emitting diode-induced fluorescence detector
      in capillary electrophoresis.
AB  - The performance of a fluorescence detector in capillary electrophoresis (CE)
      using a light-emitting diode (LED) as excitation source is reported. An
      ultraviolet LED pulsed at a repetition rate of 500 Hz, combined with a time
      discrimination and averaging acquisition system, was used. Limits of detection of
      3 and 18 fmoles (at a signal-to-noise ratio equal to 3) were achieved for
      fluorescamine-derivatized bradykinin and lysine, respectively. This system
      exhibited a linear response for a concentration range between 54 and 417 microM
      for derivatized lysine, and between 1.81 and 23.58 microM for derivatized
      bradykinin. This detection system showed to be very convenient for routine
      analytical applications.

PMID- 12210202
TI  - Chiral analysis of biogenic DL-amino acids derivatized by urethane - protected
      alpha-amino acid N-carboxyanhydride using capillary zone electrophoresis and
      micellar electrokinetic chromatography.
AB  - A new analytical method for enantioselective separation of DL-amino acids
      derivatized by N-fluorenylmethoxycarbonyl-L-alanyl N-carboxyanhydride (FMOC-L-Ala
      NCA) using capillary electrophoresis was developed. Separation parameters, such
      as composition and pH of the background electrolyte, and concentration of gamma
      cyclodextrin (in capillary zone electrophoresis) and sodium dodecyl sulfate (in
      micellar electrokinetic chromatography) were optimized. The separation method was
      validated and it suits well for purity analysis. Detection limit of the method
      was 0.2% of the minor enantiomer in the major one. The level of racemization in
      coupling during solid-phase peptide synthesis was studied using capillary
      electrophoresis with gamma-cyclodextrin as a chiral selector. The anchorage of
      the first (C-terminal) amino acid derivative to the solid supports bearing the
      hydroxylic groups is the key step of the synthesis affecting the extent of its
      racemization. FMOC-L-phenylalanine was chosen as the suitable model amino acid
      derivative making it possible to study the degree of racemization of N
      fluorenylmethoxycarbonyl-L-alanine-L-phenylalanine synthesized on different
      polymer resins, using the different condensation agents.

PMID- 12210203
TI  - Simultaneous analysis of sulfur-containing excitatory amino acids using micellar
      electrokinetic chromatography with diode array and laser-induced fluorescence
      detection.
AB  - The suitability of micellar electrokinetic chromatography (MEKC) coupled with
      diode array or laser-induced fluorescence (LIF) detection to analyze the four
      sulfur-containing excitatory amino acids (SEAA), homocysteine sulfinic acid
      (HCSA), homocysteic acid (HCA), cysteine sulfinic acid (CSA), and cysteic acid
      (CA) was investigated. 5-Carboxy-fluorescein succinimidyl ester was chosen as
      fluorescent reagent to derivatize HCSA, HCA, CSA, and CA. During method
      development, the yield of reaction dependent on pH and incubation time as well as
      the stability of the products were analyzed. The maximum yield was obtained after
      30 min using a 0.1 M borate buffer (pH 8.9) as derivatization buffer. Each
      labeled amino acid exhibited high stability at room temperature over a period of
      5 days. Baseline separation of labeled HCSA, HCA, CSA, and CA was obtained using
      a buffer consisting of 0.1 M borate, 50 mM sodium dodecyl sulfate (SDS), and 5%
      v/v methanol (pH 9.0). By applying LIF detection, limits of detection ranged from
      0.9 x 10(-10) M for HCSA to 6.0 x 10(-10) M for CA, respectively. Slightly
      modified separation conditions enabled the analysis of SEAA in cerebrospinal
      fluid in the presence of the neurotransmitters glutamate and aspartate. In
      conclusion, MEKC coupled with LIF detection is a suitable technique for the
      simultaneous and sensitive analysis of SEAA. Further work will focus on the
      validation of the method with cerebrospinal fluid as sample matrix.

PMID- 12210204
TI  - Determination of dye/protein ratios in a labeling reaction between a cyanine dye
      and bovine serum albumin by micellar electrokinetic chromatography using a diode
      laser-induced fluorescence detection.
AB  - The degree of labeling, i.e., dye/protein ratio (D/P) is important for
      characterizing properties of dye labeling with proteins. A method for the
      determination of this ratio between a fluorescent cyanine dye and bovine serum
      albumin (BSA), based on the separation of the labeling mixture using micellar
      electrokinetic chromatography with diode laser-induced fluorescence detection, is
      described. Two methods for the determination of D/P were examined in this study.
      In these methods, a hydrolysis product and impurities, which are usually
      unfavorable compounds that are best excluded for protein analysis, were utilized
      to determine the amounts of dye bound to BSA. One is a direct method in which a
      ratio of the peak area of BSA to the total peak area of all the products produced
      in the labeling reaction was used for determining the average number of dye
      molecules bound to a single BSA molecule. The other is an indirect determination,
      which is based on diminution of all peak areas related to the products except for
      the labeled BSA. These methods were directly compared by means of a
      spectrophotometric method. The experimental results show that the indirect method
      is both reliable and sensitive. Therefore, D/P values can be determined at trace
      levels using the indirect method.

PMID- 12210205
TI  - Measurement of ascorbic acid in single human neutrophils by capillary zone
      electrophoresis with electrochemical detection.
AB  - A method has been developed for the determination of ascorbic acid (AA) in
      individual human neutrophils by capillary zone electrophoresis with
      electrochemical detection at a carbon fiber microdisk bundle electrode. The
      natively easily oxidized substances such as glutathione, dopa, dopamine,
      serotonin, epinephrine do not interfere with the determination of ascorbic acid.
      A procedure of treating capillaries, which can overcome the influence of the
      adsorption of the substances in cells on the inner surface wall of the capillary
      on the migration time and the number of theoretical plates of interests, has been
      described. The average amount of AA in an individual neutrophil is 0.557 fmol,
      which is consistent with the literature value.

PMID- 12210206
TI  - DNA analysis on microfabricated electrophoretic devices with bubble cells.
AB  - Microfluidic devices with bubble cells have been fabricated on poly(methyl
      methacrylate) (PMMA) plates and have been employed for the analysis of DNA using
      polyethylene oxide (PEO) solutions. First, the separation channel was fabricated
      using a wire-imprinting method. Then, wires with greater sizes or a razor blade
      glued in a polycarbonate plate was used to fabricate bubble cells, with sizes of
      190-650 microm. The improvements in resolution and sensitivity have been achieved
      for large DNA (> 603 base pair, bp) using such devices, which depend on the
      geometry of the bubble cell. The main contributor for optimal resolution is
      mainly due to DNA migration at lower electric field strengths inside the bubble
      cell. On the other hand, slight losses of resolution for small DNA fragments have
      been found mainly due to diffusion, supported by the loss of resolution when
      separating two small solutes. With a bubble cell of 75 microm (width) x 500
      microm (depth), the sensitivity improvement up to 17-fold has been achieved for
      the 271 bp fragment in the separation of PhiX-174/HaeIII DNA restriction
      fragments. We have also found that a microfluidic device with a bubble cell of
      360 microm x 360 microm is appropriate for DNA analysis. Such a device has been
      used for separating DNA ranging from 8 to 2176 bp and polymerase chain reaction
      (PCR) products amplified after 30 cycles, with rapidity and improvements in the
      sensitivity as well as resolution.

PMID- 12210207
TI  - DNA-PKcs-OBA/Ku associate in the absence of DNA, as revealed by two-dimensional
      capillary gel electromobility shift assay.
AB  - Ors-binding activity (OBA) has been previously purified by its ability to
      specifically interact with A3/4, a 36-bp mammalian origin consensus sequence [1].
      Peptide sequence analyses identified OBA as Ku86, the largest subunit of Ku
      antigen, a heterodimeric protein (Ku70/Ku86) involved in several autoimmune
      disorders [2-5]. The affinity-purified fraction containing OBA/Ku is also
      enriched for DNA-dependent protein kinase DNA-PKcs, the catalytic subunit of the
      DNA-PK holoenzyme, of which Ku antigen is the DNA-binding subunit [6-8]. Glycerol
      gradient sedimentation analyses have demonstrated the presence of OBA/Ku in a
      high-molecular-weight complex. In order to investigate whether OBA/Ku and DNA
      PKcs are associated in this fraction, we have used a modification of the two
      dimensional gel electrophoresis technique originally described [9].
      Electromobility shift assays were developed in native capillary gels, which were
      subsequently used for sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) in the second dimension. The gels were then processed for Western
      blotting using the Ku70, Ku86 and DNA-PKcs antibodies. This approach has revealed
      the association of OBA/Ku and DNA-PKcs to give rise to the DNA-PK holoenzyme
      irrespective of the presence, or the absence of DNA. Altogether, we have proven
      the utility of this technique for the study of protein-protein and protein-DNA
      interactions.

PMID- 12210208
TI  - Biomic study of human myeloid leukemia cells differentiation to macrophages using
      DNA array, proteomic, and bioinformatic analytical methods.
AB  - A biomic approach by integrating three independent methods, DNA microarray,
      proteomics and bioinformatics, is used to study the differentiation of human
      myeloid leukemia cell line HL-60 into macrophages when induced by 12-O
      tetradecanoyl-phorbol-13-acetate (TPA). Analysis of gene expression changes at
      the RNA level using cDNA against an array of 6033 human genes showed that 5950
      (98.6%) of the genes were expressed in the HL-60 cells. A total of 624 genes
      (10.5%) were found to be regulated during HL-60 cell differentiation. Most of
      these genes have not been previously associated with HL-60 cells and include
      genes encoded for secreted proteins as well as genes involved in cell adhesion,
      signaling transduction, and metabolism. Protein analysis using two-dimensional
      gel electrophoresis showed a total of 682 distinct protein spots; 136 spots
      (19.9%) exhibited quantitative changes between HL-60 control and macrophages.
      These differentially expressed proteins were identified by mass spectrometry. We
      developed a bioinformatics program, the Bulk Gene Search System (BGSS,
      http://www.sinica.edu.tw:8900/perl/genequery.pl) to search for the functions of
      genes and proteins identified by cDNA microarrays and proteomics. The identified
      regulated proteins and genes were classified into seven groups according to
      subcellular locations and functions. This powerful holistic biomic approach using
      cDNA microarray, proteomics coupled to bioinformatics can provide in-depth
      information on the impact and importance of the regulated genes and proteins for
      HL-60 differentiation.

PMID- 12210209
TI  - Characterization of lactosylated proteins of infant formula powders using two
      dimensional gel electrophoresis and nanoelectrospray mass spectrometry.
AB  - Infant formula powders were analyzed by liquid chromatography-electrospray
      ionization-mass spectrometry (LC-ESI-MS) to assess the whey proteins quality,
      which may be altered by the heat treatment used during the processing conditions.
      Lactosylation was found to be the major chemical modification occurring in whey
      proteins. In parallel, a two-dimensional (2-D) gel electrophoresis was performed
      on the milk sample and the entire protein patterns were analyzed by nano-ESI-MS
      after cutting the different gel spots and in-gel trypsin digestion. A highly
      selective and specific tandem MS technique has been developed to characterize and
      localize up to ten lactosylation sites in beta-lactoglobulin (beta-Lg) and
      alpha(S2)-casein. alpha-Lactalbumin (alpha-La), with five lactosylated peptides,
      was found to be an interesting protein marker in the milk powder sample to detect
      chemical modification induced by the processing/storage conditions.

PMID- 12210210
TI  - Proteome analysis of human stomach tissue: separation of soluble proteins by two
      dimensional polyacrylamide gel electrophoresis and identification by mass
      spectrometry.
AB  - Two-dimensional gel electrophoresis (2-DE) maps for human stomach tissue proteins
      have been prepared by displaying the protein components of the tissue by 2-DE and
      identifying them using mass spectrometry. This will enable us to present an
      overview of the proteins expressed in human stomach tissues and lays the basis
      for subsequent comparative proteome analysis studies with gastric diseases such
      as gastric cancer. In this study, 2-DE maps of soluble fraction proteins were
      prepared on two gel images with partially overlapping pH ranges of 4-7 and 6-9.
      On the gels covering pH 4-7 and pH 6-9, about 900 and 600 protein spots were
      detected by silver staining, respectively. For protein identification, proteins
      spots on micropreparative gels stained with colloidal Coomassie Brilliant Blue G
      250 were excised, digested in-gel with trypsin, and analyzed by peptide mass
      fingerprinting with delayed extraction-matrix assisted laser
      desorption/ionization-mass spectrometry (DE-MALDI-MS). In all, 243 protein spots
      (168 spots in acidic map and 75 spots in basic map) corresponding to 136
      different proteins were identified. Besides these principal maps, overview maps
      (displayed on pH 3-10 gels) for total homogenate and soluble fraction, are also
      presented with some identifications mapped on them. Based on the 2-DE maps
      presented in this study, a 2-DE database for human stomach tissue proteome has
      been constructed and is available at
      http://proteome.gsnu.ac.kr/DB/2DPAGE/Stomach/. The 2-DE maps and the database
      resulting from this study will serve important resources for subsequent proteomic
      studies for analyzing the normal protein variability in healthy tissues and
      specific protein variations in diseased tissues.

PMID- 12210211
TI  - Mass spectrometric identification of mitochondrial oxidative phosphorylation
      subunits separated by two-dimensional blue-native polyacrylamide gel
      electrophoresis.
AB  - Blue-native polyacrylamide gel electrophoresis is a powerful tool for the
      separation of intact membrane protein complexes mainly applied to the analysis of
      the enzymes of the mitochondrial oxidative phosphorylation system (OXPHOS).
      Combined with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE), it reveals a two-dimensional pattern showing the individual subunits of
      the five OXPHOS multi-enzyme complexes. This pattern is useful in the diagnostic
      analysis of several diseases related to disorders in the oxidative
      phosphorylation system. However, in order to use this method for systematic
      diagnostic purposes and to be able to link disease with absence or reduced
      expression of specific subunits, an unambiguous identification of the individual
      subunits is necessary. In this study, we completed this task, implementing
      peptide mass fingerprinting and mass spectrometric sequence analysis. In the
      course of these analyses, we discovered a novel variant of a cytochrome c oxidase
      subunit VIc.

PMID- 12210212
TI  - Two-dimensional electrophoresis investigation of short-term response of flax
      seedlings to a cold shock.
AB  - The flax, Linum usitatissimum L., is particularly suitable for studying the
      transduction and long-term signal storage of environmental signals. To
      investigate the underlying molecular mechanisms, we have focused on the initial
      changes in the proteome since these offer the possibility of reflecting the
      plant's history of exposure to stress. In principle, this 'proteome signature'
      might be revealed by two-dimensional electrophoresis (2-DE). We have therefore
      determined the potential of 2-DE to study the kinetics of changes to the proteome
      of flax induced by a 1 min cold shock. Protein identification is difficult with
      flax because of the lack of knowledge of gene sequences. Nevertheless, 2-DE
      analysis can be informative providing the significance of changes can be
      evaluated. We have developed a stringent threshold method to determine the
      significance of changes in gels obtained with proteins extracted from hypocotyls
      at different times after cold shock. This allowed us to reliably detect and
      characterize the kinetics of a set of seven spots that responded to cold shock
      and that constitute candidates for a proteome signature of long-term signal
      storage.

PMID- 12210213
TI  - Expression patterns of antioxidant proteins in brains of patients with sporadic
      Creutzfeldt-Jacob disease.
AB  - Using two-dimensional gel electrophoresis (2-DE) and Western blot analysis, we
      were able to identify and quantify six antioxidant proteins, peroxiredoxin (Prx)
      I, Prx II, Prx III, 1-Cys Prx, putative peroxisomal antioxidant enzyme (PLP), and
      mitochondrial Mn superoxide dismutase (Mn-SOD) in two individual brain regions,
      cerebellum and frontal cortex of patients with sporadic Creutzfeldt-Jacob (sCJD).
      Among six antioxidant proteins, 1-Cys Prx showed significant increase (P > 0.05)
      in sCJD frontal cortex whereas Prx I was decreased (P > 0.01). In cerebellum,
      levels of all antioxidant proteins studied were comparable to those of controls.
      Our findings provide evidence for the link between aberrant expression of
      antioxidant proteins, 1-Cys Prx and Prx I and CJD neuropathogenesis and we
      discuss the neuropathological meaning of these dysregulated antioxidant proteins
      in sCJD brain.

PMID- 12210218
TI  - Batch electrophoretic cells with Eyring fluids: analysis of the hydrodynamics.
AB  - Mixing and dispersion phenomena caused by the carrier fluid in an electrophoretic
      cell is the main subject of this study. In particular, the effects of Joule
      heating on temperature and velocity profiles for Eyring-model fluids (EMF) are
      studied. The heat transfer is sequentially coupled with momentum transfer to
      derive an analytical expression for both the temperature and the velocity
      profiles. These results are then used to show the hydrodynamic behavior of the
      fluid in a batch electrophoretic cell. Furthermore, the results obtained are
      useful to compare with the fluid behavior of other carriers of different
      rheology, such as Newtonian fluids, power-law fluids, and viscoelastic fluids
      that obey the CEF model. The results show that EMF are potentially good carriers
      for relatively high Joule heat generation and therefore good candidates to
      control mixing inside the electrophoretic cell.

PMID- 12210219
TI  - Dispersive mixing in a batch electrophoretic cell with Eyring fluids.
AB  - The main objective of this study is analysis of dispersive mixing inside a batch
      electrophoretic cell due to Joule heating, especially for the case of non
      Newtonian carriers. To this end, a carrier fluid that follows the Eyring
      rheological model is used in the analysis of the species convective-diffusive
      equation that describes the solute motion inside the device. The hydrodynamic
      problem (Bosse, M. A. et al., Electrophoresis 2002, 23, 2149-2156) of the
      electrophoretic cell is sequentially coupled to this equation. Then, by following
      a procedure based on the area-averaging method, an effective diffusion
      coefficient is obtained. This equation is the first a priori design equation for
      devices such as the ones analyzed in this contribution. It is useful in
      determining mixing conditions for the values of the relevant parameters of the
      physical system. The results of this analysis are used to study the cell behavior
      under several conditions imposed by their main parameters. Finally, some
      suggestions are offered about the use of Eyring fluids as potential carriers
      useful for controlling dispersive mixing in batch electrophoretic cells.

PMID- 12210220
TI  - Electrokinetic transport of red blood cells in microcapillaries.
AB  - Electrokinetic flow of a suspension of erythrocytes (red blood cells, RBCs) in 20
      num cylindrical fused-silica capillaries is examined in the present work. Flow
      direction anomalies are observed experimentally and tentatively explained by the
      development of a pH gradient between the cathode well and the anode well due to
      electrolysis reactions at the electrodes. This pH gradient alters the local zeta
      potentials of both the capillary and the RBC and thus the local electroendosmotic
      liquid flow (EOF) velocities and RBC electrophoretic (EP) velocities. The two
      velocities are opposite in direction but with EOF dominating such that the RBC
      moves toward the cathode, opposite to the anode migration observed in bulk
      conditions. The opposing zeta potentials also lead to RBC aggregation at the
      anode end for low fields less than 25 V/cm. As the electroendosmotic velocity
      decreases at the anode end due to decreasing pH, pressure-driven back flow
      develops to oppose the original EOF at the remaining portions of the capillary
      ensuring constant fluid flux. When the anode EOF velocity is smaller in magnitude
      than the EP velocity, reversal of blood cell transport is observed after a short
      transient time in which a pH gradient forms. RBC velocities and pH dependencies
      on electric field and MgCl(2) concentration are presented along with data showing
      the accumulation of charge separation across the capillary. Also, a short-term
      solution to the pH gradient formation is presented that could help thwart
      development of pH gradients in micro-devices at lower voltages.

PMID- 12210221
TI  - One-, two-, and three-dimensional organization of colloidal particles using
      nonuniform alternating current electric fields.
AB  - We demonstrate here the use of nonuniform alternating current (AC) electric
      fields, generated by planar electrodes, for the organization of num-sized
      particles into one-, two-, and three-dimensional assemblies. The electrodes, with
      separations that vary from 35 to 300 num, are made of gold deposited on glass
      substrata. Latex, silica and graphite particles have been examined inside organic
      or aqueous media in order to illustrate the general applicability of the
      technique. Theoretical predictions of the particle response under the electric
      fields are experimentally confirmed for all the above particle/media combinations
      and can thus be used as a valuable design tool. The size and shape of the final
      structures are mainly dependent on the electrode shape and dimensions, but are
      also subject to the particle type and operating conditions. Particle organization
      in one dimension (strings) is achieved under conditions of positive or negative
      dielectrophoresis in the space between two energized electrodes. Two-dimensional
      particle organization (ordered, planar particles assemblies) was observed under
      conditions of negative dielectrophoresis, when quadrupole electrodes were
      employed. Moreover, when negative dielectrophoresis and stronger electric fields
      are applied (of the order of 50 kV(rms) m(-1)), three-dimensional, pyramid-like
      structures with a vertical dimension 1000-fold higher than that of the
      corresponding (planar) electrodes can be assembled. These 3-D structures can grow
      as free-standing assemblies, or inside templates etched in the substratum. The
      dielectrophoresis (DEP)-organized particle assemblies can subsequently be
      rendered permanent via the in situ fixing (cross-linking) of the individual
      particles.

PMID- 12210222
TI  - Impact of deglycosylation methods on two-dimensional gel electrophoresis and
      matrix assisted laser desorption/ionization-time of flight-mass spectrometry for
      proteomic analysis.
AB  - Glycosylation is a common post-translational modification that can add complexity
      to the proteome of many cell types. We used enzymatic and chemical methods of
      deglycosylation to treat a heavily glycosylated exoproteome sample from the
      filamentous fungus Trichoderma reesei. Deglycosylated samples were resolved on
      one-dimensional (1-D) and two-dimensional (2-D) gels in order to determine the
      effect of deglycosylation on the electrophoresis patterns and on the ability to
      identify proteins by peptide mass matching using matrix assisted laser
      desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) analysis of
      in-gel tryptic digests. We found that deglycosylation of the protein sample
      resulted in different protein patterns on 1-D and 2-D gels, reduced the
      complexity of gel patterns, and enhanced the protein identification of some
      proteins via MALDI-TOF-MS. Deglycosylation with trifluoromethanesulfonic acid
      (TFMS) was found to be more effective than enzymatic treatments. These
      deglycosylation techniques may be employed in whole proteome analysis to locate
      glycosylated proteins and assist in their identification by MS.

PMID- 12210223
TI  - Quantitative comparison and evaluation of two commercially available, two
      dimensional electrophoresis image analysis software packages, Z3 and Melanie.
AB  - While a variety of software packages are available for analyzing two-dimensional
      electrophoresis (2-DE) gel images, no comparisons between these packages have
      been published, making it difficult for end users to determine which package
      would best meet their needs. The goal here was to develop a set of tests to
      quantitatively evaluate and then compare two software packages, Melanie 3.0 and
      Z3, in three of the fundamental steps involved in 2-DE image analysis: (i) spot
      detection, (ii) gel matching, and (iii) spot quantitation. To test spot detection
      capability, automatically detected protein spots were compared to manually
      counted, "real" protein spots. Spot matching efficiency was determined by
      comparing distorted (both geometrically and nongeometrically) gel images with
      undistorted original images, and quantitation tests were performed on artificial
      gels with spots of varying Gaussian volumes. In spot detection tests, Z3
      performed better than Melanie 3.0 and required minimal user intervention to
      detect approximately 89% of the actual protein spots and relatively few
      extraneous spots. Results from gel matching tests depended on the type of image
      distortion used. For geometric distortions, Z3 performed better than Melanie 3.0,
      matching 99% of the spots, even for extreme distortions. For nongeometrical
      distortions, both Z3 and Melanie 3.0 required user intervention and performed
      comparably, matching 95% of the spots. In spot quantitation tests, both Z3 and
      Melanie 3.0 predicted spot volumes relatively well for spot ratios less than 1:6.
      For higher ratios, Melanie 3.0 did much better. In summary, results suggest Z3
      requires less user intervention than Melanie 3.0, thus simplifying differential
      comparison of 2-DE gel images. Melanie 3.0, however, offers many more optional
      tools for image editing, spot detection, data reporting and statistical analysis
      than Z3. All image files used for these tests and updated information on the
      software are available on the internet (http://www.umbc.edu/proteome), allowing
      similar testing of other 2-DE image analysis software packages.

PMID- 12210224
TI  - Quantitative evaluation of proteins in one- and two-dimensional polyacrylamide
      gels using a fluorescent stain.
AB  - The characteristics of protein detection and quantitation with SYPRO Ruby protein
      gel stain in one- and two-dimensional polyacrylamide gels were evaluated. Sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analyses of three
      different purified recombinant proteins showed that the limits of detection were
      comparable to the limits of detection with ammoniacal silver staining and were
      protein-specific, ranging from 0.5 to 5 ng. The linearity of the relationship
      between protein level and SYPRO Ruby staining intensity also depended on the
      individual protein, with observed linear dynamic ranges of 200-, 500-, and, 1000
      fold for proteins analyzed by SDS-PAGE. SYPRO Ruby protein gel stain was also
      evaluated in two-dimensional electrophoretic (2-DE) analysis of Escherichia coli
      proteins. The experiment involved analysis of replicates of the same sample as
      well as dilution of the sample from 0.5 to 50 nug total protein across gels. In
      addition to validating the 2-DE system itself, the experiment was used to
      evaluate three different image analysis programs: Z3 (Compugen), Progenesis
      (Nonlinear Dynamics), and PDQuest (Bio-Rad). In each program, we analyzed the 2
      DE images with respect to sensitivity and reproducibility of overall protein spot
      detection, as well as linearity of response for 20 representative proteins of
      different molecular weights and pI. Across all three programs, coefficients of
      variation (CV) in total number of spots detected among replicate gels ranged from
      4 to 11%. For the 20 representative proteins, spot quantitation was also
      comparable with CVs for gel-to-gel reproducibility ranging from 3 to 33%. Using
      Progenesis and PDQuest, a 1000-fold linear dynamic range of SYPRO Ruby was
      demonstrated with a single known protein. These two programs were more suitable
      than Z3 for examining individual protein spot quantity across a series of gels
      and gave comparable results.

PMID- 12210225
TI  - Comparison of lysis methods and preparation protocols for one- and two
      dimensional electrophoresis of Aspergillus oryzae intracellular proteins.
AB  - Filamentous fungal fermentations are used to produce billions of dollars of
      biochemical and pharmaceutical products annually, yet are plagued by a number of
      poorly understood problems that would benefit from proteomic analysis.
      Unfortunately, few publications are available which describe extraction of
      filamentous fungal proteins for two-dimensional electrophoresis. The goal here
      was to develop protocols for extraction of fungal proteins, from both wild-type
      and a recombinant strain of the industrially important filamentous fungi
      Aspergillus oryzae, to be used for both one- and two-dimensional electrophoresis
      (1-DE and 2-DE). Because fungal cell walls are exceptionally resistant to
      fragmentation, four lysis protocols were tested: (i) boiling in strong alkali
      solution, (ii) boiling in Sodium dodecyl surfate (SDS), (iii) chemical lysis in Y
      PER(R) reagent, and (iv) mechanical lysis via rapid agitation with glass beads in
      a Mini-BeadBeater(R). For both 1-DE and 2-DE, rapid agitation with glass beads
      was found to be the most efficient extraction method, yielding both mini- and
      large-format gels with little streaking or spot tailing, and proteins comprising
      a broad range of molecular weights and pI values.

PMID- 12210226
TI  - Proteomic evaluation of cell preparation methods in primary hepatocyte cell
      culture.
AB  - In vitro liver preparations are being used increasingly to study various aspects
      of chemical hepatotoxicity and thus have become powerful alternatives to in vivo
      toxicologic models. Primary hepatocyte culture systems are especially useful in
      screening cytotoxic and genotoxic compounds and assessing biochemical lesions
      associated with chemical exposure. We have begun to use this approach in
      combination with proteomic analysis to construct a molecular "toxicoproteomic"
      test system for a broad range of relevant and potentially toxic chemicals. Using
      a highly parallel two-dimensional electrophoretic (2-DE) protein separation
      system to analyze cells from culture systems, we previously observed significant
      variations in protein expression that were unrelated to chemical exposure. We
      hypothesized these artifactual protein alterations were the result of the
      variations in the culture conditions or cell manipulations, or both. Therefore,
      we conducted a study to assess the expression of hepatocyte proteins cultured on
      6-well plates and recovered for analysis either by scraping/pelleting or direct
      in-well solubilization. Following incubation of 1.2 x 10(6) hepatocytes in six
      well plate, recovery and solubilization of the cells and 2-DE of the solubilized
      lysates of 100 000 cells, we detected 1388 proteins in the in-well solubilized
      samples compared to 899 proteins in the washed/scraped/pelleted cell samples, a
      loss of 35%. Based on protein identification by peptide mass fingerprinting, the
      subcellular location of nearly all of the proteins whose abundance decreased were
      cytosolic and those few that increased were either microsomal, mitochondrial, or
      cytoskeletal proteins. These results emphasize the variation introduced by cell
      handling during recovery of hepatocytes from culture plates and may explain at
      least some of the artifactual differences observed in earlier in vitro
      experiments.

PMID- 12210227
TI  - Two-dimensional electrophoresis analysis of protein production during growth of
      Pseudomonas putida F1 on toluene, phenol, and their mixture.
AB  - The protein profiles of Pseudomonas putida F1 during growth on toluene, phenol,
      and their mixture were examined by two-dimensional polyacrylamide gel
      electrophoresis. Although this bacterium uses the same catabolic pathway for both
      substrates, P. putida F1 produced specific sets of proteins in response to
      toluene and phenol as single or mixed substrates. Proteins associated with growth
      on these substrates could be classified into three categories: ten Group T
      proteins were associated with the degradation of toluene, seventeen Group P
      proteins were associated with the degradation of phenol, and one Group M protein
      was observed to be associated only with toluene-phenol mixture degradation.
      During growth on the mixture, the protein profile of the cells shifted from Group
      T proteins to Group P proteins. This correlated well with the substrate
      consumption pattern, in which toluene was consumed first and growth on phenol did
      not begin until the medium was nearly depleted of toluene. Individual Group T and
      Group P protein intracellular concentrations had different transients as the
      cells grew on the mixture; seven protein levels increased, four decreased, and
      sixteen reached a maximum and then declined. The Group M protein reached a
      concentration maximum near the time when growth on phenol began. Variations in
      the maintenance of these proteins were also noted. These results demonstrate that
      cells growing on a mixture of substrates undergo significant physiological
      changes. Further investigation of these changes is expected to shed light on the
      unusual biodegradation kinetics previously observed with this mixed-substrate
      system.

PMID- 12210228
TI  - Apolipoprotein E and other cerebrospinal fluid proteins differentiate ante mortem
      variant Creutzfeldt-Jakob disease from ante mortem sporadic Creutzfeldt-Jakob
      disease.
AB  - The ability to perform an ante mortem differential diagnosis of Creutzfeld-Jakob
      disease (CJD) is aided by several clinical and molecular tests. There is a need
      for molecular tests which can reliably distinguish ante mortem variant CJD (vCJD)
      from ante mortem sporadic CJD (spCJD). A proteomics approach employing two
      dimensional protein electrophoresis is applied to the study of ante mortem CSF
      samples obtained in collaboration with the CJD Surveillance Unit and the National
      Hospital for Neurology and Neurosurgery. The sample set includes two cases of
      vCJD, three cases of spCJD and three neurologic controls. Preliminary data using
      a panel of seven molecular markers is able to distinguish vCJD from spCJD using a
      heuristic clustering algorithm. One of the molecular markers has been identified
      as apolipoprotein E which appears to be upregulated in the cerebrospiral fluid
      (CSF) of patients with vCJD as compared to spCJD. Analysis of ante mortem CSF may
      help to differentiate patients with vCJD from those patients with spCJD.

PMID- 12210229
TI  - Studies of potential cerebrospinal fluid molecular markers for Alzheimer's
      disease.
AB  - There is a need for a reliable, molecular-based ante mortem diagnostic test for
      Alzheimer's disease (AD). In this study, we examined the use of two-dimensional
      protein electrophoresis for generating molecular barcodes which may be useful for
      the clinical differentiation of AD patients from normals. We compared
      cerebrospinal fluid samples taken from AD patients with confirmed post mortem
      pathology to comparable specimens from normal volunteers. Using canonical
      correlation analysis, a panel of nine molecular markers were identified which
      segregated diseased cases from normal controls. Using the scaled volume image
      analysis variable, a principal factor analysis was also used to distinguish
      normal from AD spinal fluid, based on molecular markers identified using a
      heuristic clustering algorithm. The use of panels of molecular markers derived
      from proteomic analysis may offer the best prospect for developing molecular
      diagnostic tests for complex neurodegenerative disorders such as AD.

PMID- 12210230
TI  - Band-broadening effects in preparative free-flow zone electrophoresis.
AB  - Recently, we proposed a novel preparative free flow zone electrophoresis cell
      with extremely short residence time, which does not require external cooling
      (Poggel, M., Melin, T., Electrophoresis 2001, 22, 1008-1015). Within the new cell
      the smallest chamber dimension is not orientated perpendicular but in direction
      of the electric field. This alteration provides straight forward scale up
      opportunities. In this paper, new experimental results are reported, from which
      the limits of stable flow can be determined. The data suggest that not density
      differences but electrohydrodynamic effects are responsible for the disturbance
      of the laminar flow pattern, which is observed above a critical field strength.
      To demonstrate the efficiency of the new system, a three-component mixture
      consisting of bovine serum albumin (BSA), myoglobin and cytochrome c is
      processed, resulting in relatively high recovery and purity values of the
      different proteins, although a complete separation is not achieved.

PMID- 12210231
TI  - A single-strand conformation polymorphism method for the large-scale analysis of
      mutations/polymorphisms using capillary array electrophoresis.
AB  - We present a high-throughput single-strand conformation polymorphism (SSCP)
      method, performed on a commercially available capillary array DNA sequencer. We
      tested various sieving matrices and electrophoretic conditions, using 51 DNA
      fragments which included 45 fragments carrying only one single nucleotide
      polymorphism (SNP), 4 fragments having two SNPs and 2 fragments with insertion or
      deletion. Resolution of alleles was improved by increasing concentrations of both
      sieving matrices and buffers, and all examined polymorphisms of DNA fragments
      were detected, most of them (45 fragments) as clearly split allele peaks in
      heterozygotes. Allele frequencies of SNPs can be estimated accurately by
      determining the relative amounts of alleles in pooled DNA. In this method, the
      turn-around time for the analysis of 96 samples is less than 3 h. These results
      demonstrate that capillary array-based SSCP is an efficient and accurate
      technique for the large-scale quantitative analysis of mutations/polymorphisms.

PMID- 12210232
TI  - The separation of oligodeoxynucleotides having a single-base difference by
      affinity capillary electrophoresis using oligodeoxynucleotide- polyacrylamide
      conjugate.
AB  - We have developed an affinity capillary electrophoresis for gene mutation assay.
      We show a method for separating a mixture of oligodeoxynucleotides having single
      base difference using oligodeoxynucleotide-polyacrylamide conjugate. Because the
      conjugate behaved similarly to nonionic polyacrylamide in terms of migration
      rate, it can be used as a pseudoimmobilized affinity ligand in a polyacrylamide
      coated capillary. Oligodeoxynucleotide having an oncogene sequence and a version
      with one base substituted were completely separated by this method. The magnesium
      ion concentration was found to be a key factor in achieving efficient separation
      of oligodeoxynucleotides with the same chain length.

PMID- 12210233
TI  - Decreased protein peak asymmetry and width due to static capillary coating with
      hydrophilic derivatives of polydimethylacrylamide.
AB  - We have recently described [1] a fast and simple method for the "adsorbed static"
      coating of capillaries in capillary zone electrophoresis (CZE) with epoxy
      poly(dimethylacrylamide) (EPDMA). Protein CZE peaks in the EPDMA-coated
      capillaries exhibited a peak asymmetry similar to that obtained in capillaries
      with "covalent static" coating of polyacrylamide, suggesting a similar degree of
      adsorption of the protein onto the coating [2]. Instability of such coating at
      very low ionic strength and its stripping from the capillary in the presence of
      sodium dodecyl sulfate (SDS) also indicated a hydrophilic bonding of EPDMA to the
      silanol surface of the capillary, while its stripping in the CZE of "carboxylate
      modified" polystyrene suggested a competition between carboxylate and EPDMA for
      the hydrophilic bonds to silanol. To test those propositions, a number of EPDMA
      derived coating agents with increased hydrophilicity were synthesized. Of a
      number of the hydrophilic coating agents tested (Table 1) only two, 2% hydrolyzed
      EPDMA (HPDMA) hydrolyzed in sulfuric acid to effect the conversion of the epoxy
      groups to diols (Table 1, No. 38), and 20% EPDMA (Table 1, No. 44) exhibited for
      representative proteins a decreased peak asymmetry and width while the stability
      of the suppression of electroosmotic flow (EOF), and the stability of mobility in
      consecutive CZE runs was reduced relative to EPDMA. Coating agents which were
      more highly hydrophilic than those two (Table 1, No. 49) or less hydrophilic than
      2% EPDMA (Table 1, Nos. 57, 53, 46) provided no stable static coating.

PMID- 12210234
TI  - Isotachophoretic focusing and mass spectrometry detection as tools for improving
      the determination of aromatic sulfonates in capillary electrophoresis.
AB  - We explored isotachophoresis-capillary zone electrophoresis (ITP-CZE) with diode
      array detection on a single capillary to find out how to increase the injection
      volume and decrease the detection limits of aromatic sulfonates in CZE. The ITP
      was performed by applying a negative voltage in conjunction with hydrodynamic
      backpressure programming, and the terminating buffer was removed before the CZE
      separation, which resulted in highly sensitive determinations. The ITP increased
      the signal response of conventional hydrodynamic injection by a factor of 100,
      whereas the separation efficiency was unaffected. The limits of detection of the
      method were between 3 and 5 nugL(-1). The method was successfully used to
      determine these compounds in water samples. Experimental conditions for capillary
      electrophoresis-mass spectrometry were optimized and applied to determine
      aromatic sulfonates in water samples. These techniques enables the 2
      naphthalenesulfonate to be determined in water samples.

PMID- 12210235
TI  - Simulation and optimization of peptide separation by capillary electrophoresis
      mass spectrometry.
AB  - The potential of capillary electrophoresis (CE) for the separation of peptides
      has been extensively demonstrated in the last decade. Their correct
      characterization and sequenciation is a difficult task that can be accomplished
      using CE-mass spectrometry (CE-MS). An important limitation of CE-MS is the
      buffer choice since it should provide an adequate CE separation without ruining
      the MS signal. In this work, a new strategy is used to help to solve this
      limitation based on the combination of two different methodologies. Namely, an ab
      initio semiempirical model that relates electrophoretic behavior of peptides to
      their sequence is first used to obtain in a fast and easy way adequate CE buffers
      compatible with MS analysis. Next, CE-MS is used to separate and characterize
      peptides via the determination of their relative molecular masses. The usefulness
      of this procedure is demonstrated analyzing in a single CE-MS run a group of 10
      standard peptides of very different nature (i.e., relative molecular masses
      ranging from 132 to 1037 and isoelectric points ranging from 5.69 to 10.62). It
      is concluded that the use of this strategy can help to overcome the buffer
      limitation in CE-MS.

PMID- 12210236
TI  - Separation and characterization of human high-density apolipoproteins using a
      nonaqueous modifier in capillary electrophoresis-mass spectrometry.
AB  - The separation and characterization of human apolipoproteins and their isoforms
      was investigated using capillary electrophoresis (CE) in combination with mass
      spectrometry (MS). The focus of these analyses was the major protein constituents
      of plasma high-density lipoproteins, apolipoprotein A-I and A-II. Using aqueous
      buffers in CE, no separation between apolipoprotein A-I and A-II was observed.
      With the addition of 10-20% acetonitrile, however, the two species could be
      separated. Furthermore, multiple peaks for each of the apolipoprotein species
      were observed under these CE conditions. In order to identify and characterize
      the components, these separations were then coupled with online mass
      spectrometric detection (CE-MS). Our CE-MS results suggest that the multiple
      components observed in the acetonitrile-containing CE separation appear to be
      oxidized forms of the proteins in addition to native forms of the apolipoprotein
      A-I and A-II. These data are in agreement with previous reports that the
      methionine residues of the high-density lipoproteins (HDLs) are sensitive to
      oxidation, which in turn, alters their lipid binding characteristics and
      secondary structure. In addition to oxidized forms of the proteins,
      apolipoprotein A-II contained additional components, which varied in mass by 128
      Da. The structural differences between these components were determined by
      proteolytic digestion and tandem MS. Using these techniques, we determined that
      these components were due to truncation of the C-terminal glutamine amino acid
      residue on apolipoprotein A-II. These results demonstrate that CE in combination
      with MS is a promising technique for screening and characterizing isomers of
      plasma apolipoproteins.

PMID- 12210237
TI  - A statistical experimental design to study factors affecting enantioseparation of
      propranolol by capillary electrophoresis with cellobiohydrolase (Cel7A) as chiral
      selector.
AB  - The capillary electrophoretic enantioseparation of rac-propranolol using
      cellobiohydrolase Tr Cel7A as selector was optimized by an unbiased statistical
      experimental design. A set of pre-experiments was performed in order to identify
      critical experimental factors. In the definitive chemometric design pH, ranging
      from 5 to 7, ionic strength ranging between 0.01 and 0.02 and organic solvent
      additive in concentration from 1 to 19% v/v were studied. The response surface
      plot revealed a separation optimum in the pH interval studied. When all
      parameters were taken into account, a background electrolyte consisting of 0.016
      M bistris-acetate buffer with pH 6.5 and 17% v/v acetonitrile gave the optimum
      separation. The significance of the statistical design was confirmed by the
      generally good agreement obtained between predicted response and actual
      experimental data.

PMID- 12210238
TI  - Microemulsion electrokinetic chromatography versus capillary
      electrochromatography-UV-mass spectrometry for the analysis of flunitrazepam and
      its major metabolites.
AB  - Benzodiazepines, namely flunitrazepam and its three major metabolites, were
      successfully separated by microemulsion electrokinetic chromatography. Separation
      was achieved using an untreated fused-silica capillary (48 cm (effective length
      40 cm) x 50 num) at 25 kV; detection was performed by UV at 220 nm. The
      microemulsion system consisted of 70 mM octane, 800 mM 1-butanol, 80 mM sodium
      dodecyl sulfate (SDS) and 10 mM borate buffer, pH 9. Very high efficiencies (up
      to 400 000 plates) and resolution better than 3 were achieved. Since this
      technique is not compatible with mass spectrometry (MS) detection, a capillary
      electrochromatographic (CEC) method was developed to separate flunitrazepam and
      its metabolites. The effects of mobile phase composition and pH as well as
      voltage and temperature were systematically investigated. The optimized CEC
      method allowed the baseline separation of the investigated compounds. For the on
      line coupling of CEC with electrospray ionization-mass spectrometry, the column
      was connected to a void fused-silica capillary using a Teflon connection. This
      configuration was found efficient and suitable for hyphenation of commercial CEC
      and MS instrumentation using commercially available CEC columns.

PMID- 12210239
TI  - Investigation of capillary electrophoresis-laser induced fluorescence as a tool
      in the characterization of sewage effluent for fluorescent acids: determination
      of salicylic acid.
AB  - The investigation of emerging contaminant issues is a proactive effort in
      environmental analysis. As a part of this effort, sewage effluent is of current
      analytical interest because of the presence of pharmaceuticals and their
      metabolites and personal care products. The environmental impact of these
      components is still under investigation but their constant perfusion into
      receiving waters and their potential effect on biota is of concern. This paper
      examines a tool for the characterization of sewage effluent using capillary
      electrophoresis-laser induced fluorescence (CE-LIF) with a frequency-doubled
      laser operated in the ultraviolet (UV). Fluorescent acidic analytes are targeted
      because they present special problems for techniques such as gas chromatography
      mass spectrometry (GC-MS) but are readily accessible to CE-LIF. As an example of
      the application of this tool, salicylic acid is determined near the 100 ng/L (7 x
      10(-10) M) level in sewage effluent. Salicylic acid is a metabolite of various
      analgesics. Relatively stable in the environment, it is a common contaminant of
      municipal sewage systems. Salicylic acid was recovered from freshly collected
      samples of the effluent by liquid-liquid extraction. Confirmation of identity was
      by electron ionization GC-MS after conversion of the salicylic acid to the methyl
      ester by means of trimethylsilyldiazomethane. CE-LIF in the UV has revealed more
      than 50 individual peaks in the extract and a background response that suggests a
      large and indeterminate number of additional compounds are present. These data
      together with complementary techniques provide information on the complexity and
      components in these effluent streams.

PMID- 12210240
TI  - In-capillary derivatization and analysis of amino acids, amino phosphonic acid
      herbicides and biogenic amines by capillary electrophoresis with laser-induced
      fluorescence detection.
AB  - This paper describes a general approach for the in-capillary derivatization of
      amino compounds and the subsequent sensitive determination of the derivatives by
      micellar electrokinetic chromatography (MEKC) or capillary zone electrophoresis
      (CZE) with laser-induced fluorescence (LIF) detection. Amino acids, biogenic
      amines and amino phosphonic acid-herbicides were chosen as model analytes to
      evaluate the analytical potential of this approach. Fulfilment of the in
      capillary reaction of the analytes using LIF detection hinged on the excellent
      labeling chemistry of 5-(4,6-dichloro-s-triazin-2-ylamino)fluorescein (DTAF) and
      the good resolution achieved in the separation of derivatized analytes. Careful
      optimization of the electrophoretic conditions in the mixing step of this
      protocol allowed the determination of amino acids, biogenic amines and phosphorus
      containing amino acid-herbicides with concentration limits of detection at the
      nug/L level and relative standard deviations from 3.5 to 5.8%. The whole analysis
      is carried out within 20 min, resulting in a very simple, fast and practical
      approach for the fully automated analysis of amino acids and related compounds in
      low-volume and low-concentration samples.

PMID- 12210241
TI  - Stepwise gradient of linear polymer matrices in microchip electrophoresis for
      high-resolution separation of DNA.
AB  - The stepwise gradient of linear polymer matrices in microchannel electrophoresis
      is proposed as a means of achieving high-resolution separation of DNA samples
      containing a wide range of fragment sizes. In this method, multiple discrete
      steps in terms of polymer type or concentration are created in the microchannel
      by injecting appropriate solutions in order. The mixing of the various steps is
      found to be negligible compared to the effective length of separation channel,
      confirming that a stepwise gradient of matrices is formed. This technique is
      successfully applied to the analysis of restriction digest fragments and DNA
      ladders, and is demonstrated to provide higher resolution than the isocratic
      method, for both small and large fragments simultaneously. Even though the
      stepwise gradient is created manually, the reproducibility of the migration times
      of fragments in DNA samples is found to be quite good. Taken the separation of
      100 bp DNA ladder in three steps gradient pattern as an example, the relative
      standard deviations of migration times are respectively less than 0.53% and 3.1%
      in six consecutive injections in one channel and in different channels. The
      migration of DNA fragments in gradient mode is shown to be similar to that for
      the isocratic scheme, allowing the design of each step to be made in reference to
      existing knowledge. These promising results indicate the great potential of this
      stepwise gradient method for the analysis of DNA by microchip electrophoresis,
      offering both high resolution and good reproducibility.

PMID- 12210242
TI  - Indirect fluorescence detection of simple sugars via high-pH electrophoresis in
      poly(dimethylsiloxane) microfluidic chips.
AB  - This article describes the successful electrophoretic separation of simple
      carbohydrates in a polymeric microfluidic chip. The device fabricated in
      poly(dimethylsiloxane) (PDMS) is found to be stable in high-pH solutions. This
      allows sugars to be separated electrophoretically at pH values at or above their
      pK(a) using indirect fluorescence detection. Signal-to-noise values greater than
      10:1 were obtained using a mercury arc lamp excitation source and a fluorescein
      containing mobile phase for the detection of sugars at concentrations as low as 5
      mM. The results obtained compare favorably with published results for the same
      system using a traditional fused-silica capillary. Analysis of the data revealed
      a significant experimental sensitivity of the migration times measured in these
      PDMS devices, an aging effect that leads to considerable systematic drift over
      the course of a series of replicate measurements. These experiments highlighted
      the importance of the surface chemistry of PDMS, especially as it pertains to its
      ability to support stable electroosmotic flow within the separation device.
      Channel priming at high pH provides a necessary, but by itself insufficient,
      means by which this instability can be minimized.

PMID- 12210243
TI  - Design and performance of a microchip electrophoresis instrument with sensitive
      variable-wavelength fluorescence detection.
AB  - A modular instrument for high-speed microchip electrophoresis (MCE) equipped with
      a sensitive variable-wavelength fluorescence detection system was developed and
      evaluated. The experimental setup consists mainly of a lamp-based epifluorescence
      microscope for variable-wavelength fluorescence detection and imaging and a
      programmable four-channel bipolar high-voltage source capable of delivering up to
      +/- 10 kV per channel. The optical unit was equipped with a high-sensitivity
      photomultiplier tube and an adjustable aperture. The system was applied to MCE
      separations of flurescein isothiocyanate (FITC)-labelled amines utilizing blue
      light (450-480 nm) for excitation as well as for the separation of rhodamines
      utilizing excitation light in the green spectral region (531-560 nm). At
      optimized conditions baseline separation of four FITC-labelled amines could be
      obtained in less than 50 s at a detection limit of 460 ppt (1 nM) with a signal
      to-noise ratio of 3:1. Three rhodamines could be baseline-separated in less than
      6 s at a detection limit of 240 ppt (500 pM). The relative standard deviations of
      absolute migration times determined in repetitive MCE separations of FITC
      labelled amines were below 2.5% (n= 25). By the application of cyclodextrin
      modified electrolytes, chiral separation of FITC-labelled amines could be
      performed in seconds demonstrating the potential of microchip electrophoresis for
      chiral high-throughput screening.

PMID- 12210247
TI  - Separation and characterization of sub-microm- and microm-sized particles by
      capillary zone electrophoresis.
AB  - The analytical separation and characterization of particles in the size range of
      sub-microm and microm diameters by capillary zone electrophoresis (CZE) has been
      reviewed. The theoretical basis, on which the mobility can be interpreted to
      provide information regarding characteristics of particle surface, has shortly
      been presented. Particular emphasis was put on the model dependence of that
      interpretation and the need in most applications to forego the classical
      idealized model of spherical particles with "smooth" surfaces and to apply more
      realistic models, which take the "hairy" surface of real particles into account.
      Some highlights of the literature on the CZE of polystyrene latex microspheres,
      organic and inorganic colloids, lipoprotein particles, viruses, liposomes,
      biological membrane vesicles, and biological cells have been discussed. Also
      summarized are the reports on the particle size dependence of mobility and peak
      broadening in CZE and on electrophoretic behavior of rodlike particles and
      particle aggregates. Finally, the effects of neutral polymers in the background
      electrolyte on particle mobility and peak width are reviewed.

PMID- 12210249
TI  - Electrophoresis of cells and the biological relevance of surface charge.
AB  - Recent developments in electrophoresis of cells are reviewed. Problems and
      progress in automation and miniaturization of analytical electrophoresis
      instruments as well as in the interpretation of experimentally determined
      electrophoretic mobility (EPM) data are summarized: In recent times, the EPM
      determination techniques not only became more reliable and faster, but also more
      knowledge could be gained about the cell surface electrical properties, the
      structure of the glycocalyx as well as its influence on the cell peripheral
      regions and microenvironment by applying cell electrophoresis. In addition, ways
      are shown to solve discrepancies between physical requirements of a preparative
      cell electrophoresis procedure and the quantities of ions, which have to be
      dissolved in cell suspension media. As the modern machines allow the purification
      of untagged cells suspended in more cell friendly and physiological media, they
      are likely to be valuable tools in several useful practical applications in
      clinical transplantation, gene therapy and treatment of disease states.

PMID- 12210248
TI  - Particle separation by dielectrophoresis.
AB  - The application of dielectrophoresis to particle discrimination, separation, and
      fractionation is reviewed, some advantages and disadvantages of currently
      available approaches are considered, and some caveats are noted.

PMID- 12210250
TI  - Electrophoretic mobility of a charged spherical colloidal particle covered with
      an uncharged polymer layer.
AB  - A general expression is derived for the electrophoretic mobility of a spherical
      charged colloidal particle covered with an uncharged polymer layer in an
      electrolyte solution in an applied electric field for the case where the particle
      zeta potential is low. It is assumed that electrolyte ions as well as water
      molecules can penetrate the polymer layer. Approximate analytic expressions for
      the electrophoretic mobility of particles carrying low zeta potentials are
      derived for the two extreme cases in which the particle radius is very large or
      very small.

PMID- 12210251
TI  - Electrophoretic behavior of cerebellar granule neurons.
AB  - The electrophoresis of cerebellar granule neurons is observed, and a theoretical
      model proposed to simulate its electrophoretic behavior. We assume that the
      surface of a neuronal cell carries dissociable acidic functional groups, and the
      liquid phase contains a mixed (a:b) + (c:b) electrolyte, where a and c are the
      valences of cations and b is the valence of anions. The cations of valence c are
      allowed to bind to dissociated functional groups. The model proposed is readily
      applicable to the prediction of the surface properties of cerebellar granule
      neurons such as the density of dissociable functional groups and the equilibrium
      constant of the dissociation reaction. The applicability of the present model is
      justified by fitting it to the measured electrophoretic mobility data.

PMID- 12210252
TI  - Softness of the bacterial cell wall of Streptococcus mitis as probed by
      microelectrophoresis.
AB  - Chemical and structural complexity of bacterial cell surfaces complicate accurate
      quantification of cell surfaces properties. The presence of fibrils, fimbriae or
      other surface appendages on bacterial cell surfaces largely influence those
      properties and would therefore play a major function in interfacial phenomena as
      aggregation and adhesion. The electrophoretic softness and fixed charge density
      in the polyelectrolyte layer of nine Streptococcus mitis strains, usually
      carrying long sparsely distributed fibrils, were determined by the soft particle
      analysis using measured electrophoretic mobilities as a function of the ionic
      strength. In general, S. mitis cell surfaces are electrophoretically soft (1.0
      2.5 nm) with a fixed negative charge density of -1.2 to -4.3 x 10(6) Cm(-3).
      Further, a comparison with surfaces of other bacterial strains that are reported
      to be soft indicates that the Ohshima soft layer model does not provide
      information on the surface morphology causing the softness. The most likely
      reason is that the electroosmotic flow occurs only in the very outer region of
      thick extracellular surface layers. Nevertheless, determining the surface
      softness is essential for proper characterization of the cell surface
      electrostatics.

PMID- 12210253
TI  - Electrophoresis of solid particles at large Peclet numbers.
AB  - A theory of concentration polarization of a thin electrical double layer (DL) on
      a spherical particle is developed for the regime of large Peclet numbers which is
      realized in strong electric fields. In this regime, the concentration field
      arising outside DL is estimated under influence of diffusion and convection.
      According to the theory developed, polarization of DL at large Peclet numbers
      causes a change in the Stern potential, the formation of a dipole moment and the
      long-range potential. The diffuse layer deviates strongly from spherical symmetry
      and electroneutrality, and the screen of the surface charge is provided not only
      by the diffuse atmosphere but also by the charge induced in the convective
      diffusion layer. The effect of electric field on the induced charge gives rise to
      the additional electroosmotic slip, that was called "secondary electroosmosis".
      Thus, a nonlinear additional term for the Smoluchowski formula of electrophoretic
      velocity is based on the changes of zeta-potential and on the secondary
      electroosmotic slip. The comparison of theory with experimental results revealed
      considerable fitting.

PMID- 12210254
TI  - Electrophoresis of randomly charged particles.
AB  - The technique of "rotational electrophoresis" has been developed recently to
      measure the charge nonuniformity on Brownian particles in a suspension.
      Measurements of the angular velocity in electrophoresis are interpreted with
      electrokinetic theory to give a standard deviation of zeta potential among N
      regions on a particle. A key question is how various molecular mechanisms of
      charging could lead to charge nonuniformity on a length scale of O (100 nm).
      Simple statistical physics is used to show that although Poisson charging with
      univalent charges cannot explain recent measurements showing significant charge
      nonuniformity, random charging with multivalent charges can better explain the
      data. In addition, the result shows that a small number of charged
      "visualization" molecules can be adsorbed to a particle without impacting the
      experimental technique of rotational electrophoresis.

PMID- 12210255
TI  - Immunoelectrophoresis of red blood cells performed on microcapillary chips.
AB  - Immunoanalysis of blood cells on a microcapillary electrophoresis (nuCE) chip has
      been studied using sheep erythrocytes (ShE) as an example. Two different buffer
      solutions, the phosphate-buffered saline (PBS) and the gelatin veronal buffer
      (GVB) were examined in regard to the electrokinetic transport behavior of ShE
      suspended in these solutions inside the rectangular channel engraved on a quartz
      chip. This clarified two advantages of the use of GVB for on-chip cell
      electrophoresis: gelatin coatings prevent (i) nonspecific sticking of ShE on the
      channel wall, and cause (ii) an appreciable reduction in the zeta potential of
      the wall suppressing the electroosmotic flow of the buffer solution. As a result
      ShE suspended in the GVB can smoothly migrate from the cathode to the anode,
      which is the opposite flow direction of immunoglobulin G (IgG) antibodies under
      the physiological pH condition of 7.4. Based on these results, on-chip capillary
      cell immunoelectrophoresis of ShE and rabbit anti ShE antibodies (IgG) have been
      proposed and successfully accomplished using the GVB. It is demonstrated that the
      variation of the cell migration velocity originating from the change in the
      surface charge after binding antibodies is applicable to the fast detection of
      immune reactions and also to single-cell typing.

PMID- 12210256
TI  - Estimation of electrophoretic mobilities of red blood cells in 1-G and
      microgravity using a miniature capillary electrophoresis unit.
AB  - Electrophoretic mobilities of red blood cells (RBCs) were measured in
      microgravity using a home-made capillary electrophoresis unit, which consisted of
      two small reservoirs of 0.6 mL and a fused-silica capillary tubing with 2 cm in
      length and 50 num in inner diameter. Migration of RBCs was observed by a
      microscope at 1000 times magnification and recorded on a videotape. The
      experiments were performed during stays in microgravity (about 0.01 G), which
      lasted 20 s and were attained by parabolic flights of an aircraft. On average,
      the electrophoretic mobilities of RBCs determined in microgravity were about 30%
      higher than those measured at 1-G condition irrespectively whether the cells were
      suspended in saline or serum during measurements. This difference might be
      explained as being mainly due to the cell floating in microgravity. Morphological
      changes of RBCs may contribute partly to the difference, while the variation in
      viscosity of the medium under microgravity could play only a minor role.

PMID- 12210257
TI  - Determination of individual microsphere properties by capillary electrophoresis
      with laser-induced fluorescence detection.
AB  - Capillary electrophoresis with postcolumn laser-induced fluorescence detection
      was used to individually detect 6.0, 1.0, 0.5, and 0.2 num diameter polystyrene
      microspheres and individually measure their electrophoretic mobility. The
      analysis of a nanoliter-size volume from a microsphere suspension results in an
      electropherogram characterized by several narrow spikes in a well-defined
      migration time window. Each spike is associated with one microsphere because,
      when one single microsphere is introduced into the capillary by
      micromanipulation, the electropherogram has only one spike in the same migration
      time window. The distributions of individual measurements resulting from an
      electropherogram were used to evaluate the reproducibility from run to run,
      observe the effect of sodium dodecyl sulfate (SDS) added to the running buffer,
      and to investigate the origin of electrophoretic dispersion. As expected from the
      interactions between microspheres and SDS, the addition of this surfactant to the
      running buffer narrowed the range and shifted the average electrophoretic
      mobility to more negative values. After evaluating common sources of broadening
      in capillary electrophoresis, electrophoretic dispersion was attributed to
      microsphere heterogeneity. Unlike electropherograms displaying Gaussian-like
      profiles, the two-dimensional representations of the individual measurements
      provide a new alternative to evaluate and study electrophoretic-related
      properties of microspheres.

PMID- 12210258
TI  - Monitoring the migration behavior of living microorganisms in capillary
      electrophoresis using laser-induced fluorescence detection with a charge-coupled
      device imaging system.
AB  - Remarkably high apparent peak efficiencies (10(6)-10(9) theoretical plates per
      meter) in capillary electrophoresis (CE) could be achieved in the separation of
      two different kinds of bacteria and Baker's yeast using poly(ethylene oxide) as a
      necessary buffer additive. In these applications no deliberate stacking procedure
      was implemented. Seemingly, the investigated organisms in this study behave
      differently than molecules under an applied electric field. For molecules, these
      extremely high efficiencies are very unusual. Using a 488 nm argon-ion laser
      coupled to a charge-coupled device (CCD) camera it was possible to monitor the
      migration behavior of stained microorganisms over a length of 10 cm. This part
      simulates the very beginning of the CE run. In specific cases 60-70% of the
      monitored detection window could be filled with analyte without significant loss
      in peak efficiency. For a mixture of two different microorganisms the occurring
      separation process could be followed in detail. The effect of buffer
      concentration, polymer type, polymer molecular weight, polymer concentration, pH,
      and the effect of injection time was investigated. The expansion of fast and
      reproducible CE separations to other unicellular organisms may become a powerful
      tool in microbiological science and technology.

PMID- 12210259
TI  - Dielectrophoretic studies of the activation of human T lymphocytes using a newly
      developed cell profiling system.
AB  - Human T lymphocytes were stimulated using phorbol myristate acetate and
      ionomycin. Twenty-four hours post-activation the cells were harvested for DNA
      content and for measurements using a newly developed cell profiling system
      employing dielectrophoresis. This system provides individual cell size and
      dielectrophoresis data for statistically relevant numbers of control and
      activated cells. From this it was determined that the mean membrane specific
      capacitance decreased from 13.49 (+/- 4.72) mF/m(2) to 10.62 (+/- 5.13) mF/m(2).
      This can be related to a 21.3% reduction in the effective membrane surface area
      associated with membrane topography (e.g. reduction of membrane associated
      microvilli, blebs and folding), or to other changes of membrane architecture,
      following cell activation. From cytometric determinations of DNA content, it was
      concluded that these effects were related to a 3.0-fold decrease of cells in S
      phase, and a 1.5-fold increase in G1 cells. This work demonstrates the powerful
      potential of using dielectrophoresis as a noninvasive tool to follow
      physiological changes that accompany transmembrane signaling events.

PMID- 12210260
TI  - Multistage electrophoresis II: treatment of a kinetic separation as a
      pseudoequilibrium process.
AB  - An electrophoresis device is described which separates cells, particles, proteins
      and other separands by collecting samples having decreasing electrophoretic
      mobility in a train of inverted cavities while an electric field is applied
      between the inverted cavities and a sample cuvette containing a mixture of cells,
      particles, proteins or other separands. A circular plate is provided for the
      inverted cavities, and this circular plate is rotated to collect fractions. The
      system utilizes an innovative purification method that combines free
      electrophoresis and multistage extraction in an instrument capable of separating
      living cells, particles, and proteins in useful quantities at high
      concentrations. Most multistage processes are based on equilibrium separations,
      but electrophoresis is a kinetic separation; therefore, a pseudoequilibrium
      paradigm was developed for use in optimizing separation parameters including
      number of stages and electrophoresis time per stage. This paradigm allows the
      application of McCabe-Thiele type analysis, and it was calculated, for example,
      that two separands differing by 20% in electrophoretic mobility can be purified
      to 95% purity with acceptable yield in about seven stages. Laboratory experiments
      demonstrated a 95% purification in four stages of a separand originally present
      at 4% when electrophoretic mobilities differed by 80%.

PMID- 12210261
TI  - Application of intracellular microelectrophoresis to analysis of the influence of
      the low-level microwave radiation on electrokinetic properties of nuclei in human
      epithelial cells.
AB  - Intracellular microelectrophoresis was applied to investigate the electrokinetic
      properties of human buccal epithelium cell nuclei after exposure of cells to
      microwaves of wavelengths of 8 mm (f = 37.5 GHz) and 16 mm (f = 18.75 GHz) at a
      surface power density of 0.2 mW/cm(2). Irradiated or nonirradiated cells were
      suspended in a flat microelectrophoretic chamber and exposed to an electric field
      of 15 V/cm at a current flow of 0.1 mA. The cells, whose nuclei altered their
      intracellular location towards the anode of the externally applied electric
      field, were considered to have negatively charged nuclei. The percentage of cells
      with electrophoretically movable nuclei was determined as the value of
      electronegativity of cell nuclei (ENN). Microwaves induced changes of ENN during
      irradiation of 15-60 s. If cells of a donor had an elevated initial level of ENN,
      it decreased during irradiation. On the contrary, if cells of another donor had a
      low initial ENN level, irradiation induced ENN increase. No significant
      difference between the action of microwaves of wavelengths of 8 mm and 16 mm was
      found. However, microwave irradiation caused an increase in membrane permeability
      for the in vivo dye indigo Carmine in cells of all donors irrespectively of the
      initial levels they showed. This suggests that electrokinetic properties of
      nuclei in cells do not only depend on cell membrane permeability.

PMID- 12210262
TI  - Probing cell surface charge by scanning electrode potential.
AB  - A static mercury electrode was used for measurement of double-layer charge
      displacement signals caused by living plant cells of the unicellular marine alga
      Dunaliella tertiolecta. By scanning the electrode potential a point is reached
      where the charge density of a plant cell compensates the electrode charge
      density. The experimentally determined values of surface charges for unicellular
      marine alga Dunaliella tertiolecta cells are -0.63 and -0.75 nuC/cm(2) in 0.1 M
      NaCl and 1 M NaCl solutions, respectively.

PMID- 12210263
TI  - Cell adhesion and the negative cell surface charges in embryonic cells of the
      starfish Asterina pectinifera.
AB  - Spherical blastomeres of starfish embryos begin to adhere to neighboring
      blastomeres and to become columnar in shape from the 7(th) or 8(th) cleavage
      onward. Studying development of embryos in the presence of LiCl, we found that
      developmental changes in cell-cell contacts were accelerated by LiCl. In order to
      learn why LiCl increased the adhesiveness between blastomeres, the negative
      surface charge density was estimated by the method of cell electrophoresis. It
      turned out that the electrophoretic mobility (EPM) of all blastomeres isolated
      from LiCl-treated embryos before the 512-cell stage was remarkably decreased. At
      the mid-gastrula stage, however, when constituent cells were connected with each
      other more tightly, the EPM was significantly retarded irrespectively whether the
      cells had been isolated from control or from LiCl-treated embryos. From these
      results of cell electrophoresis we conclude that reduction of the negative
      surface charge density may be one of the important factors that enhance the
      adhesion of starfish embryonic cells.

PMID- 12210264
TI  - Characterization of the early stages of programmed cell death in maize root cells
      by using comet assay and the combination of cell electrophoresis with annexin
      binding.
AB  - An emerging topic in plant biology is whether plant cells display similar
      elements of programmed cell death (PCD) as animal cells do. We have studied cell
      death in maize roots exposed to cold stress by using fluorescence microscopy,
      terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling
      (TUNEL), DNA gel electrophoresis, single cell gel electrophoresis (SCGE), cell
      electrophoresis, and annexin binding techniques. The results showed that cell
      death in maize root cells triggered by cold stress was accompanied by a subset of
      features characteristic of animal PCD such as nuclear condensation and
      fragmentation, and oligonucleosomal DNA fragmentation. In addition to DNA
      laddering and TUNEL positivity, a "comet" pattern indicative of DNA breakage
      appeared as short as after one day of treatment. The maize root cell PCD process
      was also accompanied by an increase in negative surface charge of the dying cells
      due to exposure of phosphatiolylserine (PS) from inner to outer membrane. After
      annexin binding, however, the enhanced electrophoretic mobility (EPM) of the
      dying cells decreased nearly to normal values. This result suggests that the
      combination between cell electrophoresis and annexin binding provides a
      quantitative method for monitoring PS exposure during plant PCD.

PMID- 12210265
TI  - Particle electrophoresis as a tool to understand the aggregation behavior of red
      blood cells.
AB  - Red blood cell (RBC) electrophoresis measurements in polymer solutions have
      recently been introduced as a promising approach for investigating polymer-cell
      interactions near the RBC surface. A polymer-poor depletion layer near the RBC
      has been demonstrated: for depletion layers thicker than the double layer,
      viscosity within the depletion layer, rather than suspending medium viscosity,
      affects cell mobility. Using a well-documented model of sepsis in rats, we have
      induced RBC membrane damage, and then measured the electrophoretic mobility of
      rat RBC from control and septic animals. Mobility measurements were carried out
      for cells suspended in polymer-free buffer and in 0.5-2% solutions of dextran 500
      (500 kDa molecular mass); RBC aggregation in autologous plasma and in dextran 500
      was also studied. Our results indicate: (i) as anticipated from prior studies,
      the aggregation of RBC from septic animals is markedly enhanced (p<0.001) in
      plasma and in 0.5-1% dextran; (ii) the mobility of septic RBC in polymer-free
      buffer was identical to control, whereas cells from septic animals had lower
      mobilities in 0.5% dextran; (iii) Over the range studied (0.5-2%), the mobility
      of RBC from septic animals was less sensitive to increases of dextran
      concentration and hence medium viscosity. These mobility-aggregation findings can
      be partially interpreted in terms of a depletion model for RBC aggregation;
      alterations of RBC surface charge and the hydrodynamic friction within the cell's
      glycocalyx may also be involved. In overview, we believe that these results
      suggest the merits of microelectrophoresis for exploring protein or polymer
      behavior near biological particles and the potential value of future studies for
      understanding cell-cell interactions.

PMID- 12210266
TI  - Electrophoretic behavior of individual nuclear species as determined by capillary
      electrophoresis with laser-induced fluorescence detection.
AB  - We determined the feasibility of using capillary electrophoresis with postcolumn
      laser-induced fluorescence (CE-LIF) detection to characterize electrophoretic
      properties of isolated cell nuclei and impurities present in nuclear fractions.
      These fractions were isolated from NS-1 mouse hybridoma cells, stained with
      hexidium iodide, a DNA intercalating dye, and analyzed by CE-LIF detection. The
      corresponding electropherograms display two features: (i) broad peaks (6-90 s
      wide) caused by the cell culturing media and by free-DNA intercalated with
      hexidium iodide, and (ii) a large number of narrow peaks (180 ms wide), resulting
      from DNA associated with individual intact or disrupted nuclei. We confirmed that
      the narrow peaks were not caused by contaminating mitochondria. The overall
      electrophoretic mobility range of disrupted nuclei is 0 to -5 x 10(-4)cm(2)/Vs,
      while intact nuclei seem to have mobilities in the -1.5 to -3.5 x 10(-4)cm(2)/Vs
      range. Furthermore, the highly sensitive CE-LIF method reveals a high abundance
      of disrupted nuclei that cannot be directly observed by confocal microscopy.

PMID- 12210267
TI  - Different temperature sensitivity of endosomes involved in transport to lysosomes
      and transcytosis in rat hepatocytes: analysis by free-flow electrophoresis.
AB  - Endocytosis at reduced temperature has been used to define and characterize
      endosome subpopulations. Thus, the temperature sensitivity of endosome
      subpopulations involved in transport to lysosomes and transcytosis in rat
      hepatocytes was analyzed applying endosome labeling in the isolated perfused rat
      liver with route-specific ligands in combination with temperature shift
      protocols. Free-flow electrophoresis (FFE) that separates membranes and
      organelles based on their surface charge was then applied to isolate functional
      endosomes. Using asialoorosomucoid (ASOR) and polymeric immunoglobulin A (pIgA)
      as specific ligands of the lysosomal and transcytotic route, respectively, two
      distinct endosome subpopulations along either pathway were separated by FFE. Upon
      a short (1-3 min) internalization at 37 degrees C, 125I-ASOR and fluorescein
      isothiocyanate (FITC)-pIgA were colocalized in common early endosomes. Following
      a 5-10 min chase of the ligands at 37 degrees C endosomes labeled with 125I-ASOR
      were separated from endosomes labeled with FITC-pIgA, indicative of two distinct
      late compartments along the lysosomal and transcytotic route. Internalization at
      16 degrees C resulted in accumulation of both ligands in common early endosomes
      and, consequently, in inhibition of transport to lysosomes and transcytosis. When
      125I-ASOR or 125I-pIgA were first chased into late compartments at 37 degrees C
      and the temperature was subsequently lowered to 16 degrees C, biliary secretion
      of 125I-ASOR-derived counts was arrested, while biliary output of 125I-pIgA
      continued. In summary, ASOR en route to lysosomes can be blocked in early as well
      as in late endosomes at 16 degrees C, while biliary secretion of pIgA cannot be
      prevented by temperature reduction once the ligand had been transferred from
      early to late compartments.

PMID- 12210268
TI  - Isolation of peroxisomal subpopulations from mouse liver by immune free-flow
      electrophoresis.
AB  - Peroxisomes (PO) are a heterogeneous population of cell organelles which in
      mammals are most abundant in liver and kidney. Commonly, differential and density
      gradient centrifugation are used for their isolation which, however, give only
      rise to the so-called "heavy" PO with a buoyant density of 1.22-1.24 g/cm(3).
      Subpopulations other than the heavy PO which are also present in both of these
      tissues have escaped adequate purification because of their sedimentation
      characteristics which are close to those of other major organelles, in particular
      microsomes. Since the purification of these subpopulations has become an
      essential task in view of the putative importance of peroxisomal subpopulations
      in the biogenesis of this organelle, alternatives to density gradient
      centrifugation are required. Recently, we have introduced such a novel approach,
      named immune free flow electrophoresis (IFFE). IFFE combines the advantages of
      eletrophoretic separation with the high selectivity of an immune reaction. It
      makes use of the fact that the electrophoretic mobility of a subcellular
      particle, complexed with an antibody directed against the cytoplasmic domain of
      one of its integral membrane proteins is greatly diminished, provided the pH of
      the electrophoresis buffer is adjusted to pH approximately 8.0, the pI of
      immunoglobulin G (IgG) molecules. pH-values other than 8.0 proved to be less
      efficient, probably because IgG molecules only focus at pH 8.0 but are scattered
      at any other. Applying IFFE to heavy and light mitochondrial as well as
      microsomal fractions of rat liver not only regular PO (rho = 1.22-1.24 g/cm(3))
      but also other subpopulations could be isolated. To substantiate the validity of
      this approach, we now have subfractionated mouse liver homogenates accordingly.
      Of the PO subpopulations collected, mainly that obtained from the heavy
      mitochondrial fraction differed in its composition of matrix and membrane
      proteins as revealed by immunoblotting. This is in line with the data reported on
      rat liver thus confirming the potential of IFFE in the isolation of distinct
      subpopulations of hepatic PO.

PMID- 12210269
TI  - Electrokinetic and light scattering properties of pea and Chlamydomonas
      reinhardtii thylakoid membranes: effect of phytohemagglutinin.
AB  - The effects of phytohemagglutinin (PHA) and illumination on the surface charge
      densities and 90 degrees light scattering properties of pea and Chlamydomonas
      reinhardtii thylakoids were investigated. The electrophoretic mobility (EPM) of
      pea thylakoids decreased after treatment by various concentrations of PHA at
      ionic strengths of I = 0.01 and I = 0.02, while that of C. reinhardtii thylakoids
      remained stable except for a drop after treatment by PHA at a concentration of 6
      ng/mL in a medium with an ionic strength of I = 0.01. Illumination did not
      influence the EPM of untreated thylakoids. However, if the EPM of thylakoids had
      been retarded by pretreatment with PHA, light exposure stimulated a recovery of
      the reduced negative surface charge density up to at least the initial values. In
      addition to reducing EPM, PHA also induced a decrease of the basal light
      scattering property of pea thylakoids, which is an indicator of thylakoid
      aggregation. The physiological role of the membrane surface charges of thylakoid
      particles in lectin regulated processes of thylakoid stacking and activity is
      discussed.

PMID- 12210271
TI  - Gender-specific molecular heterosis of dopamine D2 receptor gene (DRD2) for
      smoking in schizophrenia.
AB  - We examined the genetic effect of DRD2 A1 allele in 167 Korean schizophrenics in
      relation to their smoking habit. Although there was no apparent difference in the
      genotype distributions of DRD2 gene among the female schizophrenics (n = 66), the
      male counterpart (n = 101) showed significant differences in their genotype
      distributions. The comparison between male smoking and non-smoking patients
      showed the difference in genotype distribution (P = 0.010) with a higher
      prevalence of A1 allele (P = 0.020) and frequency of heterozygotes (P = 0.005),
      but not frequency of the A1 allele. The A1A2 heterozygotes male showed
      significantly higher smoking rate compared to the A1A1 or A2A2 homozygotes male,
      and non-smokers were deficient in heterozygotes. By contrast, among female
      schizophrenics, the heterozygotes showed a lower smoking rate than homozygotes
      and there were more heterozygotes in non-smokers. The deviation from Hardy
      Weinberg expectations was observed in male and female non-smokers showing quite
      opposite profiles. Highly significant differences were seen between male and
      female non-smokers in A1 prevalence (P = 0.001), genotype distribution (P =
      0.00011), and frequency of heterozygotes (P = 0.00003), but not in A1 frequency.
      The analyses from both male and female as one group showing no significant
      difference in the genotype distributions between smokers and non-smokers could be
      explained by the gender difference in the genetic effect of DRD2 A1 allele. Our
      findings present the gender-specific molecular heterosis of DRD2 gene in relation
      specifically to the smoking status of schizophrenic patients. They indicate the
      importance of heterosis and gender effects that should be taken into
      consideration for the association studies.

PMID- 12210272
TI  - Linkage of chromosome 13q32 to schizophrenia in a large veterans affairs
      cooperative study sample.
AB  - Several prior reports have suggested that chromosomal region 13q32 may harbor a
      schizophrenia susceptibility gene. In an attempt to replicate this finding, we
      assessed linkage between chromosome 13 markers and schizophrenia in 166 families,
      each with two or more affected members. The families, assembled from multiple
      centers by the Department of Veterans Affairs Cooperative Studies Program,
      included 392 sampled affected subjects and 216 affected sib pairs. By DSM-III-R
      criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%)
      were classified as schizoaffective disorder, depressed. The families had mixed
      ethnic backgrounds. The majority were northern European-American families (n =
      62, 37%), but a substantial proportion were African-American kindreds (n = 60,
      36%). Chromosome 13 markers, spaced at intervals of approximately 10 cM over the
      entire chromosome and 2-5 cM for the 13q32 region were genotyped and the data
      analyzed using semi-parametric affected only linkage analysis. For the combined
      sample (with race broadly defined and schizophrenia narrowly defined) the maximum
      LOD score was 1.43 (Z-score of 2.57; P = 0.01) at 79.0 cM between markers
      D13S1241 (76.3 cM) and D13S159 (79.5 cM). Both ethnic groups showed a peak in
      this region. The peak is within 3 cM of the peak reported by Brzustowicz et al.
      [1999: Am J Hum Genet 65:1096-1103].

PMID- 12210273
TI  - Association analysis of an (AC)n repeat polymorphism in the GABA(B) receptor gene
      and schizophrenia.
AB  - The human gamma-aminobutyric acid type B (GABA(B)) receptor gene is a candidate
      gene for schizophrenia due to its chromosomal location and neurobiologic roles.
      In the present study, association analyses of genetic polymorphisms of the
      GABA(B) receptor gene with schizophrenia were carried out in 102 unrelated
      schizophrenic patients and 100 healthy controls, using a polymerase chain
      reaction-based, single-strand conformational polymorphism analysis. Although the
      Ala20Val and Gly489Ser mutations were not found in our samples, we found a novel
      polymorphism of (AC)n dinucleotide repeats located approximately 1.6 kb upstream
      from the translational start site. No significant difference in allele
      frequencies was found between controls and patients with schizophrenia (P =
      0.0587) using the Monte Carlo method. Significant differences were found between
      controls and patients with continuous-course schizophrenia (P = 0.0019), and
      between controls and patients with a positive family history of psychoses (P =
      0.0015). These differences, however, were not significant after Bonferroni
      correction. These data did not support our hypothesis that polymorphisms of the
      GABA(B) receptor gene may confer vulnerability for schizophrenia.

PMID- 12210274
TI  - Spatial working memory deficits in schizophrenia patients and their first degree
      relatives from Palau, Micronesia.
AB  - Spatial working memory deficits associated with dorsolateral prefrontal
      dysfunction have been found in Caucasian samples of schizophrenia patients and
      their first-degree relatives. This study evaluated spatial working memory
      function in affected and unaffected members of multiplex schizophrenia families
      from the Republic of Palau to determine whether the spatial working memory
      deficits associated with schizophrenia extend to this non-Caucasian population.
      Palau is an isolated island nation in Micronesia with an elevated prevalence of
      schizophrenia and an aggregation of cases in large multigenerational families.
      Our objective was to evaluate the potential for spatial working memory function
      to serve as one of multiple endophenotypes in a genetic linkage study of these
      Palauan schizophrenia families. A spatial delayed response task requiring
      resistance to distraction and a sensorimotor control task were used to assess
      spatial working memory in 32 schizophrenia patients, 28 of their healthy first
      degree relatives, and 19 normal control subjects. Schizophrenia patients and
      their relatives were significantly less accurate than normal control subjects on
      the spatial delayed response task but not on the sensorimotor control task. On
      both tasks, patients and relatives were slower to respond than the normal
      controls. There were no age or gender effects on accuracy, and working memory
      performance in schizophrenia patients was not significantly correlated with
      medication dosage. In summary, spatial working memory deficits that have been
      found in Caucasian schizophrenia patients and relatives were confirmed in this
      isolated Pacific Island family sample. These results suggest that spatial working
      memory deficits may be a potentially useful addition to the endophenotypic
      characterization of family members to be used in a comprehensive genome wide
      linkage analysis of these Palauan families.

PMID- 12210275
TI  - Brain volumes in familial and non-familial schizophrenic probands and their
      unaffected relatives.
AB  - Structural brain abnormalities are consistently reported in schizophrenic
      subjects but the etiology of these abnormalities remains unclear. We tested the
      contribution of genetic predisposition and obstetric complications to the
      structural brain abnormalities found in schizophrenic probands and their
      relatives. MRI scans were carried out on 35 schizophrenic probands from families
      multiply affected with the disorder, and 63 of their unaffected relatives,
      including 10 parents who appeared to transmit genetic risk to their children; as
      well as 31 schizophrenic probands from families with no other affected members,
      33 of their unaffected relatives; and finally 68 controls. Volumetric
      measurements of whole brain, lateral ventricles, third ventricle, cerebellum, and
      temporal lobes were completed for each subject. The impact of obstetric
      complications on brain structure was assessed across the gradient of presumed
      genetic predisposition. Both groups of schizophrenic probands displayed
      enlargement of the lateral and third ventricles, and there was a gradient of
      ventricular enlargement amongst the unaffected relatives in proportion to their
      likelihood of carrying schizophrenic genes. Ventricular enlargement was largely
      confined to males in both probands and unaffected relatives. Obstetric
      complications were associated with ventricular enlargement only in the familial
      probands. Non-familial probands displayed reduced volume of the temporal lobes
      bilaterally. In families with several schizophrenic members, ventricular
      enlargement is a marker for genetic liability, particularly in males. Individuals
      inheriting the susceptibility to schizophrenia appear particularly prone to
      develop ventricular enlargement in response to obstetric complications.

PMID- 12210276
TI  - Aromatic amino acid hydroxylase genes and schizophrenia.
AB  - Phenylalanine hydroxylase (PAH), which catalyzes the conversion of phenylalanine
      to tyrosine, shares physical, structural and catalytic properties with tyrosine
      hydroxylase (TH) and tryptophan hydroxylase (TPH) that catalyze the rate-limiting
      steps in the biosynthesis of the neurotransmitters dopamine, noradrenaline, and
      serotonin. Because these neurotransmitter systems have all been implicated in the
      pathophysiology of schizophrenia, the aromatic amino acid hydroxylases are among
      the likely candidates for genes associated with schizophrenia. A mutation in the
      functionally critical tetrahydrobiopterin cofactor binding domain of the PAH gene
      had been identified in African-American patients with the diagnosis of
      schizophrenia, and biochemical analyses suggested that this mutation has
      physiological consequences related to amine neurotransmitter function. DNA
      sequencing of the highly conserved cofactor binding domain of the PAH, TH, and
      TPH genes in African-American subjects with schizophrenia and unrelated, never
      mentally ill subjects from the NIMH Schizophrenia Genetics Initiative, was
      undertaken to assess the concordance of mutant genotype with psychiatric
      phenotype. The K274E mutation was observed in the PAH gene cofactor binding
      domain, and several polymorphisms were identified in adjacent intronic regions of
      the PAH, TH, and TPH genes. All of the genetic variants observed were represented
      in the schizophrenia group and in the never mentally ill group. Genetic
      evaluation of the family members of subjects with the PAH K274E mutation showed
      that all individuals with the K274E mutation also exhibited the PAH L321L
      polymorphism in the catalytic domain of the PAH enzyme.

PMID- 12210277
TI  - Alteration of branch site consensus sequence and enhanced pre-mRNA splicing of an
      NMDAR1 intron not associated with schizophrenia.
AB  - Aberrant splicing of pre-mRNA is recognized to account for a significant minority
      of disease-causing mutations. The N-methyl-D-aspartate receptor (NMDA) subunit
      gene R1 (NMDAR1) is alternatively spliced to produce eight length variants. In an
      examination of the NMDAR1 as a candidate gene in schizophrenia, a presumed
      microdeletion/insertion (del/ins) was observed in intron 10 of an African
      American male near a weak putative branch-site consensus sequence. Although exon
      10 is not known to be alternatively spliced, the del/ins was posited to alter
      splicing efficiency. If splicing were abolished and intron retention occurred, an
      in-frame translation product of more than 250 amino acids was predicted. To
      explore splicing efficiency, mini genes were examined through primer-extension
      analyses in NIH293 embryonic kidney cell cultures. Rather than disruption of
      splicing, the del/ins allele exhibited a fivefold enhancement in splicing. In an
      association analysis with additional schizophrenic cases and unaffected controls,
      all of African-American descent, the mutant allele was observed at equivalent
      frequencies. A family study also did not support cosegregation of the variant
      allele with psychiatric disease.

PMID- 12210278
TI  - Allele sharing for schizophrenia and schizo-affective disorder within a region of
      Homo sapiens specific XY homology.
AB  - A case (based upon an association with cerebral asymmetry) has been presented for
      a gene for psychosis within the Xq21.3/Yp region of homology that is specific to
      Homo sapiens. We tested this hypothesis using the pentanucleotide marker DXYS 156
      that is located within this region. In 84 families affected by schizophrenia or
      schizo-affective disorder no tendency toward increased allele sharing amongst
      siblings was observed (chi(2) = 0.002). We conclude either that this region does
      not include a gene predisposing to psychosis or that if it does, the relevant
      variation is epigenetic rather than sequence-based. With respect to the latter
      possibility we draw attention to the recent evolutionary history of the Xq21.3/Yp
      region. Genes within the region are in transition to protection from X
      inactivation and therefore may be epigenetically labile.

PMID- 12210279
TI  - Possible effect of the APOE epsilon 4 allele on the hippocampal volume and
      asymmetry in schizophrenia.

PMID- 12210280
TI  - DRD4 and novelty seeking: results of meta-analyses.
AB  - Studies of the association between polymorphisms within and near the dopamine D4
      receptor (DRD4) gene and novelty seeking (NS) have produced inconsistent results,
      raising questions about the strength of the relationship and the methodological
      conditions under which the relationship holds. We conducted three meta-analyses
      of existing studies to provide formal statistical measures of the strength of the
      DRD4-NS relationship. Results provided no support for a relationship between NS
      and the presence of the 7-repeat allele of the VNTR polymorphism. A small
      positive effect, however, was found for long repeats of the same polymorphism.
      The most promising findings were obtained for the relationship with the -521 C/T
      promoter polymorphism, for which the analysis showed an effect size of 0.32. The
      positive findings are consistent with a polygenic model of influence on
      fundamental personality dimensions.

PMID- 12210281
TI  - Norepinephrine transporter and alpha(2c) adrenoceptor allelic variants and
      personality factors.
AB  - It has been suggested that reward dependence, as measured by the Tridimensional
      Personality Questionnaire (TPQ), is related to central noradrenergic activity, a
      proposition supported by two studies of urinary norepinephrine metabolite. In the
      current investigation, 190 normal young Han Chinese were examined, with genetic
      polymorphisms determined for the norepinephrine transporter (1287G/A) and the
      alpha(2c)-adrenoceptor (Del322-325) to test the association with TPQ personality
      traits. No significant association was demonstrated for these two polymorphisms
      and any of the TPQ personality-factor scores, including reward dependence and its
      subscales. Our negative findings suggest that the investigated polymorphisms of
      the norepinephrine transporter and the alpha(2c) adrenoceptor do not play a major
      role in the reward-dependence personality trait as assessed by TPQ.

PMID- 12210282
TI  - Investigation of Notch3 as a candidate gene for bipolar disorder using brain
      hyperintensities as an endophenotype.
AB  - The purpose of the study was to consider MRI hyperintensities as a potential
      endophenotype for bipolar disorder (BPD) and to investigate Notch3 (CADASIL) as a
      candidate gene for BPD. MRI scans were performed on 21 members of a family with a
      high incidence of BPD. Two-point and multipoint linkage analyses were performed
      and two exons of Notch3 were investigated with SSCP. Fifteen of 21 family members
      had MRI hyperintensities, including all bipolar patients and six family members
      with no affective illness. Two-point linkage analysis yielded negative results
      for all models. Multipoint linkage analysis yielded negative results except for
      Model 1a, in which a maximal LOD score was -1.24. A mutation screen of Exons 3
      and 4 was negative. Notch3 does not appear to be a candidate gene for BPD in this
      family.

PMID- 12210284
TI  - No evidence of linkage or association between the norepinephrine transporter
      (NET) gene polymorphisms and ADHD in the Irish population.

PMID- 12210283
TI  - Lack of association of a single-nucleotide polymorphism of the mu-opioid receptor
      gene with anxiety-related traits: results from a cross-sectional study of adults
      and a longitudinal study of children.
AB  - There is evidence from animal experiments that the mu- and delta-opioid receptors
      may play a role in anxiety and depression. It might therefore be expected that
      functional polymorphisms of these genes in humans are associated with anxiety and
      depression. We investigated a single-nucleotide polymorphism (Asn40Asp) of the mu
      opioid receptor gene (OPRM1). This association was investigated in two samples:
      1) a cross-sectional survey of 867 community-living adults aged 18-79 years who
      were assessed for anxiety and depression symptoms and related personality traits;
      and 2) a longitudinal study of childhood temperament in which 660 children were
      followed from infancy to the mid-teens and assessed for anxiety-related
      temperament and behavior problems. The data did not support a role for the
      Asn40Asp polymorphism in anxiety and depression, despite adequate statistical
      power to detect small effects.

PMID- 12210285
TI  - No evidence for linkage of liability to autism to HOXA1 in a sample from the CPEA
      network.
AB  - A recent study by Ingram et al. [2000b: Teratology 62:393-405] suggests a
      (His)73(Arg) polymorphism (A:G) in HOXA1 contributes substantially to a liability
      for autism. Using 68 individuals diagnosed with Autism Spectrum Disorders, they
      found a significant dearth of G homozygotes and biased transmission of G alleles
      from parents to affected offspring, especially from mothers. Because the
      connection between HOXA1 and liability to autism is compelling, we attempted to
      replicate their finding using a larger, independent sample from the Collaborative
      Programs of Excellence in Autism (CPEA) network. In our data, genotype
      frequencies conform to Hardy-Weinberg equilibrium; allele transmissions meet
      Mendelian expectations; and there is no obvious sex-biased allele transmission.
      Based on our sample size, calculations suggest that we would have at least 95%
      power to detect linkage and association even if the A:G polymorphism were to
      account for only 1% of the heritability of autism. Therefore, although we cannot
      exclude the possibility that the samples in the two studies are intrinsically
      different, our data from our sample argue against a major role for HOXA1
      (His)73(Arg) in liability to autism.

PMID- 12210287
TI  - Evidence for parent of origin effect in late-onset Alzheimer disease.
AB  - Evidence for a parent of origin effect in Alzheimer disease was obtained from a
      sample of 148 sibships on which affection status of the parents was sought using
      family history interviews. The parent study recruited families with two or more
      affected sibs for late onset AD utilizing rigorous diagnostic criteria. In 74
      families, there was evidence of an affected parent, 49 maternal and 25 paternal.
      Genome scan data were analyzed for the sample as a whole and for the maternal and
      paternal families separately, using Genehunter-ASM. Seven regions with Z(lr)
      scores >or=2 were identified, four in maternal families (chr. 10,12,19,20) and
      three in paternal families (chr. 1,7,13). With the exception of the chromosome 10
      finding, analysis by parent of origin greatly increased evidence of linkage in
      areas showing no linkage in the overall analyses. For example, a chr. 12 region
      reached a LOD = 2.29 among maternal families whereas the same region showed a LOD
      = 0.3 when all families were analyzed together. The strongest findings among
      maternal families (chr. 10 and 12) were followed up with fine mapping that
      resulted in an increase in maximum LOD scores from 2.7-3.2 on chr. 10, and 2.29
      2.42 on chr. 12. These analyses highlight the importance of parent of origin
      effects in late-onset AD families and identify several genomic regions that may
      include genes linked to late-onset AD specific to disease transmission from the
      mother and require further investigation.

PMID- 12210286
TI  - No evidence for a susceptibility locus for idiopathic generalized epilepsy on
      chromosome 18q21.1.
AB  - A recent genome-wide scan showed strong evidence for a major locus for common
      syndromes of idiopathic generalized epilepsy (IGE) at the marker D18S474 on
      chromosome 18q21.1 (LOD score 4.5/5.2 multipoint/two-point). The present
      replication study tested the presence of an IGE locus in the chromosomal region
      18q21.1. Our linkage study included 130 multiplex families of probands with
      common IGE syndromes. Eleven microsatellite polymorphisms encompassing a
      candidate region of 30 cM on either side of the marker D18S474 were genotyped.
      The two-point homogeneity LOD score for D18S474 showed strong evidence against
      linkage at the original linkage peak (Z = -18.86 at theta(m = f) = 0.05),
      assuming a recessive mode of inheritance with 50% penetrance. Multipoint
      parametric heterogeneity LOD scores < -2 were obtained along the candidate region
      when proportions of linked families greater than 35% were assumed under recessive
      inheritance. Furthermore, non-parametric multipoint linkage analyses showed no
      hint of linkage throughout the candidate region (P > 0.19). Accordingly, we
      failed to support evidence for a major IGE locus in the chromosomal region 18p11
      18q23. If there is a susceptibility locus for IGE in this region then the size of
      the effect or the proportion of linked families is too small to detect linkage in
      the investigated family sample.

PMID- 12210288
TI  - No association between the neuronal nitric oxide synthase gene polymorphism and
      Alzheimer Disease.
AB  - Nitric oxide synthase (NOS) has been implicated in the pathogenesis of Alzheimer
      disease (AD). To examine the role of the neuronal NOS (nNOS) gene in AD, patients
      (n = 139) and control subjects (n = 101) were genotyped for the nNOS dinucleotide
      polymorphism. No association was demonstrated for AD and this particular nNOS
      polymorphism.

PMID- 12210289
TI  - Williams syndrome cognitive profile also characterizes Velocardiofacial/DiGeorge
      syndrome.

PMID- 12210290
TI  - Tardive dystonia and genetic polymorphisms of cytochrome P4502D6 and dopamine D2
      and D3 receptors: a preliminary finding.
AB  - Tardive dystonia is an uncommon but intractable and distressing complication of
      neuroleptic treatment. It is suggested that individual predisposing vulnerability
      plays a major role in the development of the side effect. This study aimed to
      investigate relationship tardive dystonia and several genetic factors such as
      polymorphism of cytochrome P4502D6, and receptor polymorphisms of dopamine D(2)
      (TaqI A and -141C Ins/Del polymorphisms) and D(3) (Ser(9)Gly polymorphism). Nine
      patients with tardive dystonia were genotyped for these genetic polymorphisms. No
      specific genotypes or alleles were overpresented in the patients. This study
      suggests that these polymorphisms are not related to the development of tardive
      dystonia.

PMID- 12210291
TI  - Coffin-Lowry syndrome: a 20-year follow-up and review of long-term outcomes.
AB  - The Coffin-Lowry syndrome has become well established since the first report of
      affected patients by Coffin et al. [1966: Am J Dis Child 112:205-213]. Since that
      time over a hundred cases have been reported and the responsible gene has been
      identified. However, there remains a paucity of long-term follow-up information
      on older patients with which to counsel affected families about prognosis. There
      is also much to be learned about genotype-phenotype correlations. In 1982 we
      reported 12 patients (including carrier mothers) from eight families, one of whom
      had died about the time the paper was written. Recently, we have been able to
      obtain follow-up information on six of the affected patients and one of the
      carrier mothers. A number of important complications have occurred, including
      premature death, loss of ambulation, and quadriplegia. This paper updates the
      medical histories of our patients and summarizes the clinically important
      complications that have been reported in patients with Coffin-Lowry syndrome.
      There are few data on patients over the age of 30, and much more longer term
      follow-up is required.

PMID- 12210293
TI  - Identification of uniparental disomy in phenotypically abnormal carriers of
      isochromosomes or Robertsonian translocations.
AB  - Carriers of either homologous or non-homologous acrocentric rearrangements are at
      an increased risk for aneuploidy, and, thus, for uniparental disomy (UPD).
      Abnormal phenotypes due to genomic imprinting are associated with UPD for the
      acrocentric chromosomes 14 and 15. The purpose of this study was to determine the
      prevalence of UPD in a population with acrocentric rearrangements (either an
      isochromosome or a Robertsonian translocation) and abnormal phenotypes. Fifty
      individuals were studied. Of the 50 rearrangements, two were homologous
      rearrangements and both showed UPD. Forty-eight were non-homologous Robertsonian
      translocations, of which two showed UPD. This study demonstrates that UPD
      explains the abnormal phenotypes in some balanced carriers of acrocentric
      rearrangements. Our results and the large number of case reports in the
      literature suggest that patients with abnormal phenotypes and acrocentric
      rearrangements of chromosomes 14 or 15 should be tested for UPD.

PMID- 12210292
TI  - HFE based re-evaluation of heterozygous hemochromatosis.
AB  - Homozygosity for the C282Y mutation in the HFE gene is strongly associated with
      hereditary hemochromatosis. More than one subject out of 10 in the general
      population is a heterozygote for the C282Y mutation. In this study, we address
      whether or not conclusions drawn from HLA-based family studies regarding the
      expression of heterozygous hemochromatosis are applicable to C282Y heterozygotes.
      The correlation between HLA-inferred and HFE genotypes and the variation of serum
      iron tests according to HFE genotype and other factors were studied in persons
      from well-characterized hemochromatosis pedigrees. Subjects were tested for both
      C282Y and H63D mutations. The following factors were studied: age, sex, alcohol
      consumption, body mass index, liver function tests, serum lipids and glucose,
      serum iron, transferrin saturation, and ferritin. HLA-inferred heterozygotes were
      C282Y heterozygotes in only 70% and compound heterozygotes (i.e., heterozygotes
      for both C282Y and H63D) in 20%. C282Y heterozygotes did not differ from wild
      type homozygotes in terms of serum iron tests. Only compound heterozygotes
      presented with slightly increased transferrin saturation. On the other hand,
      increased serum ferritin was strongly associated with overweight or lipidic or
      glucose abnormalities. C282Y heterozygotes selected from family studies do not
      have greater serum iron tests than wild type homozygotes, except for compound
      heterozygotes, and therefore should not require special followup. The discovery
      of abnormal iron tests in a C282Y heterozygote should lead to workup for other
      causes of iron overload.

PMID- 12210294
TI  - Review and meta-analysis of systematic searches for uniparental disomy (UPD)
      other than UPD 15.
AB  - All systematic searches for uniparental disomy (UPD) so far published and
      comprising clinically defined populations (Silver-Russell syndrome/primordial
      growth retardation (SRS/PGR) (n = 14), multiple malformations (n = 2), or rare
      syndromes (n = 12)) or situations at risk (confined placental mosaicism (CPM) (n
      = 13), spontaneous abortions (n = 6), additional marker chromosomes (n = 15),
      balanced non-Robertsonian translocations (n = 3), or balanced Robertsonian
      translocations (n = 15)) were reviewed. In many studies clinical and/or
      cytogenetic information on fluorescent in situ hybridization (FISH) results was
      very scarce. Meta-analysis concerning an adequate number of cases was possible
      for SRS/PGR, CPM, additional marker chromosomes, and balanced Robertsonian
      translocations only. As expected, the highest risk for UPD was found in cases
      with translocations between homologous acrocentric chromosomes (11 cases with UPD
      of 15 investigated) and in CPM due to a meiotic error (25 of 51 cases). In
      prenatal investigations or in cases with a normal phenotype, translocations
      between nonhomologous acrocentric chromosomes implied a risk for UPD of less than
      0.5%. The risks for maternal UPD 7 in cases with SRS/PGR, for UPD 15 in cases
      with an additional inv dup(15) marker chromosome, and for UPD of any chromosome
      in cases with multiple malformation/mental retardation were approximately 5.5%,
      and approximately 1.3%, respectively. Searches for UPD in well-defined syndromes
      (Brachmann-De Lange syndrome, Sotos syndrome, Rett syndrome, Weaver syndrome, or
      XX true hermaphroditism) were disappointing. Not a single case was found.

PMID- 12210295
TI  - Setleis syndrome: three new cases and a review of the literature.
AB  - Setleis syndrome is characterized by cutis aplasia or atrophic skin at the
      temples, which is said to resemble forceps marks. There may also be a coarse
      facial appearance, anomalies of the eyelashes and eyebrows, and periorbital
      puffiness. The mouth has a typical appearance with large lips, inverted "V"
      contour, and downturned overly defined corners. Patients usually have normal
      intelligence. Here are presented three cases with features of Setleis syndrome.
      One is an apparently isolated case; the others are father and son. All three have
      developmental delay. This second family is a further example of autosomal
      dominant inheritance in Setleis syndrome. These patients also suggest that
      developmental problems may be a more common manifestation than previously
      described. Two of the patients are the first described of Pacific Island descent.

PMID- 12210296
TI  - Behavioral phenotypes in four mental retardation syndromes: fetal alcohol
      syndrome, Prader-Willi syndrome, fragile X syndrome, and tuberosis sclerosis.
AB  - Behavioral phenotypes were studied in four mental retardation syndromes using the
      Developmental Behavior Checklist (DBC). The four samples comprised fetal alcohol
      syndrome (FAS), Prader-Willi syndrome (PWS), fragile X syndrome (FRAX), and
      tuberosis sclerosis (TSC). Both on the item and the subscale level, there were
      clear behavioral differentiations across the four syndromes. FAS and FRAX proved
      to be most clearly differentiated from the other two samples, with PWS and TSC
      showing lower scores and less abnormal behavior profiles. Neither intelligence
      nor gender nor age contributed to variations in the number of behavior
      abnormalities. It was concluded that the DBC as a quantitative approach
      contributes significantly to the differentiation of behavioral phenotypes in
      various mental retardation syndromes.

PMID- 12210297
TI  - Growth charts for nose length, nasal protrusion, and philtrum length from birth
      to 97 years.
AB  - Craniofacial measurements are an integral part in the evaluation of a dysmorphic
      patient. Since the clinical impression can be misleading, dysmorphic features
      should be validated by quantitative criteria wherever possible. Anthropometric
      measurements have been used in the characterization of many dysmorphic syndromes.
      However, data on normal craniofacial measurements is sparse and incomplete. In
      this study, we present normal values for nose size and philtrum length based on
      measurements on 2,500 healthy individuals of central European origin, ranging in
      age from zero to 97 years.

PMID- 12210298
TI  - Diagnostic dilemmas in the short rib-polydactyly syndrome group.
AB  - The short rib-polydactyly syndromes are a group of lethal skeletal dysplasias
      with autosomal recessive inheritance characterized by markedly short ribs, short
      limbs, usually polydactyly, and multiple anomalies of major organs. At least four
      types have been recognized. The radiological findings of 10 cases are presented.
      Each fetus or stillbirth has some of the radiological features of the four
      established types of short rib-polydactyly syndrome and raises diagnostic
      dilemmas in differentiating these entities. The overlapping phenotypes of these
      fetuses supports the previously suggested hypothesis that the different subtypes
      of the short rib-polydactyly syndrome group are not single entities, but rather
      part of a continuous spectrum with variable expressivity.

PMID- 12210299
TI  - Tetrasomy Y by structural rearrangement: clinical report.
AB  - Poly-Y karyotypes, except for 47,XYY, are rare events in humans. For instance, Y
      chromosome tetrasomy has been reported 10 times, 2 of which were by structural
      rearrangement. We present a 2-year-and-4-month-old boy who was referred for
      cytogenetic assessment because of global psychomotor delay. The GTG- and CBG
      banded karyotypes on PHA-stimulated lymphocytes showed two cell populations, one
      of them contained two identical isodicentric Y chromosomes, which was seen in 93%
      of metaphases analyzed, and a 45,X cell line (7%). This was confirmed by FISH
      with probes DYZ3 (recognizing the centromeric region of the Y chromosome), 91H4.5
      (recognizing Yp11.2), and DYZ1 (recognizing Y heterochromatin in Yq12). The
      breakpoint has occurred near the telomeric end of the heterochromatic region.
      Therefore, the karyotype is mos 47,X,idic(Y)(q12)x2[123]/45,X[9]. This is the
      second time that such a karyotype has been reported. This chromosomal anomaly was
      formed most likely by a U-type exchange. Clinical features included speech delay,
      short stature, brachycephaly, large ears, bilateral epicanthal folds,
      hypertelorism, delayed teeth eruption, bilateral radio-ulnar synostosis,
      bilateral fifth finger clinodactyly, normal external genitalia, and impulsive
      behavior. The father had normal phenotype and karyotype. A review of the
      tetrasomy Y patients is presented. All patients with Y chromosome tetrasomy
      exhibit some degree of mental retardation, various skeletal abnormalities, and
      facial dysmorphism. Nevertheless, the correlation between karyotype and phenotype
      is not yet well defined since few cases have been reported. This clinical report
      will be helpful in defining the phenotypic range associated with tetrasomy Y.

PMID- 12210300
TI  - Familial reciprocal translocation t(7;16) associated with maternal uniparental
      disomy 7 in a Silver-Russell patient.
AB  - We present the case of a maternal heterodisomy for chromosome 7 in the daughter
      of a t(7;16)(q21;q24) reciprocal translocation carrier. The proband was referred
      to the hospital for growth retardation and minor facial dysmorphism without
      mental retardation. A diagnosis of Silver-Russell syndrome was suspected.
      Chromosomal analysis documented a 46,XX,t(7;16)(q21;q24)mat chromosome pattern.
      Microsatellite analysis showed a normal biparental inheritance of chromosome 16
      but a maternal heterodisomy of chromosome 7. Occurrence of uniparental disomy
      (UPD) is a well-recognized consequence of chromosomal abnormalities that increase
      the rate of meiotic nondisjunction, mainly Robertsonian translocations and
      supernumerary chromosomes. Although reciprocal translocations should,
      theoretically, be also at increased risk of UPD, only three cases have been
      reported so far. However, because the association between uniparental disomy and
      reciprocal translocation may exist with an underestimated frequency, prenatal
      diagnosis is recommended when clinically relevant chromosomes for UPD are
      involved.

PMID- 12210301
TI  - Velo-cardio-facial syndrome: clinical report of a 70-year-old woman.
AB  - A clinical report is presented of a 70-year-old female in whom, after more than
      40 years residential psychiatric care, the diagnosis of velo-cardio-facial
      syndrome (VCFS) was ultimately established; the patient has a 46, XX.ish del
      (22)(q11.2q11.2)(D(22)S(75)-) karyotype. It is advocated that a rather specific
      psychopathological profile is present in patients with VCFS, for which the term
      psychopathological phenotype is introduced, that should include data from
      genetics, neuropathology, development, psychology, and psychiatry.

PMID- 12210302
TI  - Primary hypothyroidism and osteopenia associated with Neuhauser syndrome.
AB  - We report on a patient affected by Neuhauser megalocornea-mental retardation
      (MMR) syndrome, presenting with most of the major manifestations of this
      disorder, in association with primary hypothyroidism and osteopenia. These
      symptoms, previously reported in single patients, could be discrete features of
      MMR syndrome.

PMID- 12210303
TI  - Greenberg dysplasia (hydrops-ectopic calcification-moth-eaten skeletal
      dysplasia): prenatal ultrasound diagnosis and review of literature.
AB  - A second pregnancy of young, nonconsanguineous parents of Macedonian ethnic
      origin was examined by ultrasound. Polyhydramnios and hydrops fetalis were found
      as well as severe short limb, short stature, and cystic hygroma of the neck. An
      artificial abortion was performed at the age of 23 weeks. The radiological
      features included moth-eaten severely shortened long bones and ectopic
      calcifications of long bones, vertebral column, ribs, pelvis, larynx, trachea. In
      addition, the fetus had large head with depressed nasal bridge, severe
      platyspondyly, and short barrel-shaped trunk. Light microscopy demonstrated lack
      of chondrocyte columns and disorganization of the cartilaginous architecture.
      This is the seventh reported case of this rare form of lethal skeletal dysplasia.

PMID- 12210304
TI  - Apparently new osteodysplastic and primordial short stature with severe
      microdontia, opalescent teeth, and rootless molars in two siblings.
AB  - A Thai man and his sister affected with a newly recognized syndrome of
      proportionate primordial short stature are reported. The patients had severe
      intrauterine and postnatal growth retardation, prominent nose and nasal bridge,
      small pinnae, large sella turcica, areas of hypo- and hyperpigmentation of skin,
      dry and thin scalp hair, and long and straight clavicles. Ivory epiphyses and
      cone-shaped epiphyses of the hands were found when they were young, but most of
      them disappeared as they grew up. Scaphoid and trapezium had angular appearance.
      The second toes were unusually long. Distal symphalangism of toes and
      barchymesophalangy of fingers were noted. The findings that appear to distinguish
      this syndrome from the previously reported syndromes are long second toes,
      opalescent and rootless teeth, severe microdontia, severely hypoplastic alveolar
      process, and unerupted tooth. The mode of inheritance is suspected to be
      autosomal recessive.

PMID- 12210305
TI  - Early detection of severe cholestatic hepatopathy in COACH syndrome.
AB  - COACH syndrome is a disorder with cerebellar vermis hypoplasia, oligophrenia,
      ataxia, coloboma, and hepatic fibrosis. Sixteen cases with certain COACH
      diagnosis have been reported so far. Neurologic abnormalities are the first
      symptoms in most cases. The majority of cases were diagnosed late in childhood or
      adolescence. Complications of the hepatopathy contribute extensively to the
      morbidity and lethality in the course of the disease. Major complications are
      portal hypertension, esophageal varices, and gastrointestinal bleeding. We report
      of a child with only mild neurologic symptoms, but severe hepatic fibrosis with
      cholangiopathy, and review the literature. This is the first description of
      profound cholestatic hepatopathy in a very young child with COACH syndrome. The
      patient was found to have cerebellar vermis hypoplasia, unilateral optical nerve
      coloboma, mild dysmorphic signs, and a ventricular septum defect. Routine
      laboratory investigations eventually revealed elevated liver enzymes. Prothrombin
      time was abnormal. Ultrasound scan of the liver was normal. Hepatotropic viral
      infections were excluded. We performed a liver biopsy at the age of 16 months,
      confirming an early stage of cirrhosis with septal fibrosis and pseudolobules,
      inflammatory infiltrates, signs of cholestasis, and reduced numbers of
      intrahepatic bile ducts. Early detection and differentiation of liver pathology
      are important in COACH syndrome. Progressive destructive cholangiopathy may
      contribute to hepatic fibrosis in COACH syndrome. Liver disease can be severe
      even in cases with mild neurologic deficits.

PMID- 12210306
TI  - Cyst-like cerebral lesions in tuberous sclerosis.
AB  - Known brain manifestations of tuberous sclerosis (TSC) are cortical sclerotic
      tubera, giant cell astrocytomas, subependymal calcified nodules in the lateral
      walls of the lateral ventricles, and white matter heterotopias. In addition,
      small cyst-like lesions in the white matter have been described. We report on
      three TSC patients with hitherto undescribed large cyst-like cerebral lesions in
      subcortical and white matter locations. We emphasize that cystoid brain
      degeneration is a rare but typical cerebral manifestation of TSC and suggest
      that, in patients with such lesions, TSC should be taken into consideration.

PMID- 12210307
TI  - Estimate of prevalence of proximal 15q duplication syndrome.

PMID- 12210308
TI  - Another family with nonspecific X-linked mental retardation (MRX78) maps to
      Xp11.4-p11.23.

PMID- 12210309
TI  - Transmission of the mitochondrial t8993c mutation in a new family.

PMID- 12210310
TI  - Central nervous system abnormalities in Kabuki (Niikawa-Kuroki) syndrome.

PMID- 12210311
TI  - Distortion of female meiotic segregation and reduced male fertility in human
      Robertsonian translocations: consistent with the centromere model of co-evolving
      centromere DNA/centromeric histone (CENP-A).

PMID- 12210312
TI  - Does a Jewish type of Cohen syndrome truly exist?

PMID- 12210313
TI  - Human homologues of Osr1 and Osr2 are not involved in a syndrome with distal limb
      deficiencies, oral abnormalities, and renal defects.

PMID- 12210314
TI  - Limb/pelvis hypoplasia/aplasia with skull defect (Schinzel phocomelia):
      distinctive features and prenatal detection.

PMID- 12210316
TI  - Onset age of Parkinson disease.

PMID- 12210318
TI  - Familial interstitial 570 kbp deletion of the UBE3A gene region causing Angelman
      syndrome but not Prader-Willi syndrome.
AB  - Angelman syndrome (AS) is a disorder of psychomotor development caused by loss of
      function of the imprinted UBE3A gene. Since the paternal UBE3A copy is regularly
      silent, only mutations inactivating the maternal copy cause AS. Among 1,272
      patients suspected of AS, we found one with an isolated deletion of the UBE3A
      gene on the maternally inherited chromosome. Initial DNA methylation testing at
      the SNURF-SNRPN locus in the patient revealed a normal pattern. The deletion was
      only detected through allelic loss at microsatellite loci D15S1506, D15S122, and
      D15S210, and confirmed with fluorescence in situ hybridization (FISH) using
      bacterial artificial chromosome (BAC) probes derived from the loci. It extends
      approximately 570 kilobase pairs (kbp), encompassing the UBE3A locus, and is
      flanked by loci PAR/SN and D15S986. The deletion is familial, and haplotype
      studies suggest that a great grandfather of the index patient already carried
      this deletion, and that it causes AS when inherited through the female germline
      but not Prader-Willi syndrome (PWS) when paternally inherited. Our findings
      support the hypothesis that the functional loss of maternal UBE3A gene activity
      is sufficient to cause AS and that the deleted region does not contain genes or
      other structures that are involved in PWS. Finally, this case highlights that
      methylation tests can fail to detect some familial AS cases with a recurrence
      risk of 50%.

PMID- 12210319
TI  - Infantile hypotonia as a presentation of Rett syndrome.
AB  - Rett syndrome (RTT) is classically defined by meeting certain clinical diagnostic
      criteria. It affects mostly females, and one possible pathogenic mechanism was
      considered to involve mitochondrial function. This was based on the finding of
      ultrastructural alterations in the mitochondria and decreased respiratory chain
      enzyme activity. However, the principal etiology of RTT has since been found to
      be mutations in the MECP2 gene, which is located on the X chromosome. Molecular
      analysis has allowed the phenotype of MECP2 mutations to be broadened beyond RTT
      to include girls who have mild mental retardation, autism, and an Angelman
      syndrome phenotype, as well as males with severe encephalopathy. We present a
      girl with a previously described mutation in the MECP2 gene whose phenotype is of
      atypical RTT. She presented with hypotonia and developmental delay in infancy
      without a clear period of normal development. As part of her evaluation for
      hypotonia, a muscle biopsy and respiratory chain enzyme analysis showed a slight
      decrease in respiratory chain enzyme activity consistent with previous reports.
      This report supports broadening the phenotype of patients who should be
      considered for MECP2 mutation analysis to include cases of developmental delay
      and hypotonia without evidence of an initial period of normal development.
      Furthermore, it supports the hypothesis of an underlying secondary defect in
      energy metabolism contributing to the pathogenesis of RTT.

PMID- 12210320
TI  - Distribution of CGG repeats and FRAXAC1/DXS548 alleles in South American
      populations.
AB  - In order to assess the molecular variability related to fragile X (FMR1 locus),
      we investigated the distribution of CGG repeats and DXS548/FRAXAC1 haplotypes in
      normal South American populations of different ethnic backgrounds. Special
      attention was given to Amerindian Wai-Wai (Northern Brazil) and Ache (Paraguay),
      as well as to Brazilian isolated communities of African ancestry, the remnants of
      quilombos. Comparison of samples from quilombos, Amerindians, and the ethnically
      mixed, but mainly European-derived population of Sao Paulo revealed that the 30
      copy allele of the fragile X gene is the most frequent in all groups. A second
      peak at 20 repeats was present in the population of Sao Paulo only, confirming
      this as a European peculiarity. The distribution of DXS548 and FRAXAC1 alleles
      led to a high expected heterozygosity in African Brazilians, followed by that
      observed in the population of Sao Paulo. Amerindians showed the lowest diversity
      in CGG repeats and DXS548/FRAXAC1 haplotypes. Some rare alleles, for example, the
      148-bp (FRAXAC1) or 200-bp (DXS548) variants, which seem to be almost absent in
      Europe, occurred in higher frequencies among African Brazilians. This suggests a
      general trend for higher genetic diversity among Africans; these rarer alleles
      could be African in origin and would have been lost or possibly were not present
      in the groups that gave rise to the Europeans.

PMID- 12210321
TI  - Fine mapping of the IBD1 locus did not identify Crohn disease-associated NOD2
      variants: implications for complex disease genetics.
AB  - Crohn disease (CD) is a chronic relapsing inflammatory condition of the
      gastrointestinal tract. Recently, polymorphisms in NOD2 (CARD15), a gene mapping
      to the chromosome 16 IBD1 susceptibility locus, have been associated with
      susceptibility to CD. One group identified the gene by using classic positional
      cloning methods. Here, we report linkage and fine mapping analyses using 27
      microsatellite markers encompassing the IBD1 susceptibility locus in 131 CD
      affected sibling pairs, and a simplex family cohort. No evidence for linkage was
      observed, and microsatellite markers close to NOD2 did not show association.
      However, significant association was confirmed in 294 CD trios for the NOD2
      variants Arg702Trp and Leu1007fsinsC. Our fine mapping study of the IBD1 locus
      did not enable us to identify NOD2 as a CD gene, despite the presence of
      association with disease-causing alleles. This study illustrates the difficulties
      facing microsatellite linkage and linkage disequilibrium mapping methods for
      identifying disease genes in complex traits.

PMID- 12210322
TI  - Morphometric appraisal of the skull of Caroline Crachami, the Sicilian "dwarf"
      1815?-1824: a contribution to the study of primordial microcephalic dwarfism.
AB  - The skeleton of Caroline Crachami is a rare historical example of primordial
      microcephalic dwarfism (PMD). Studies show the condition to be heterogeneous,
      with at least three types, for which the assessment criteria rely on descriptive
      evaluations and/or simple measures with regard to cranial features. Advances in
      noninvasive imaging allow for a more complete morphometric examination of the
      skull of Caroline Crachami with the aim of clarifying aspects of the condition.
      In the present study, the skull of Caroline Crachami was three-dimensionally
      imaged with computed tomography (CT) and reconstructed in virtual space.
      Coordinates for a number of measurements were taken to represent interesting
      anatomies with an emphasis on those measures not easily replicated on the skull
      itself. Volumes of the endocranial cavity and sella turcica were also computed.
      These data were compared with normative values taken from the literature and
      measured from CT images of the Bosma collection. Findings indicate that the
      general size of the skull is equivalent to that of a 6- to 8-month-old, that the
      endocranial volume and cranial base angle are commensurate with that of a
      newborn, and that the sella volume is the same as that for an 8- to 15-month-old.
      Apart from these traits, the skull was well proportioned and within the range of
      normal variation for a skull aged between 2-9 years. We conclude that further
      quantitative analysis on related skulls is warranted in the study of PMD using
      the methods and techniques described.

PMID- 12210324
TI  - Duplication of 8p23.2: a benign cytogenetic variant?
AB  - We describe a duplication of the 8p23.2 band in seven individuals from four
      families. The duplication was recognizable as an enlarged 8p23.2 band on G-banded
      chromosomes at the 550 band level. It was transmitted from a parent to offspring
      in three of the four families in which both parents were karyotyped. Each proband
      in the four families had the enlarged band and showed various phenotypic
      abnormalities, but the abnormalities were inconsistent. Chromosomal and
      interphase fluorescence in situ hybridization (FISH) analysis of the enlarged
      band region defined a 2.5-Mb duplicated segment common to all seven individuals
      studied. Interphase FISH analysis of peripheral blood lymphocytes from 50
      unrelated normal individuals showed the duplication in three individuals. In view
      of these findings, it is most likely that the 8p23.2 duplication we described is
      a normal variant.

PMID- 12210323
TI  - Novel OCTN2 mutations: no genotype-phenotype correlations: early carnitine
      therapy prevents cardiomyopathy.
AB  - Primary systemic carnitine deficiency or carnitine uptake defect (OMIM 212140) is
      a potentially lethal, autosomal recessive disorder characterized by progressive
      infantile-onset cardiomyopathy, weakness, and recurrent hypoglycemic hypoketotic
      encephalopathy, which is highly responsive to L-carnitine therapy. Molecular
      analysis of the SLC22A5 (OCTN2) gene, encoding the high-affinity carnitine
      transporter, was done in 11 affected individuals by direct nucleotide sequencing
      of polymerase chain reaction products from all 10 exons. Carnitine uptake (at Km
      of 5 microM) in cultured skin fibroblasts ranged from 1% to 20% of normal
      controls. Eleven mutations (delF23, N32S, and one 11-bp duplication in exon 1;
      R169W in exon 3; a donor splice mutation [IVS3+1 G > A] in intron 3; frameshift
      mutations in exons 5 and 6; Y401X in exon 7; T440M, T468R and S470F in exon 8)
      are described. There was no correlation between residual uptake and severity of
      clinical presentation, suggesting that the wide phenotypic variability is likely
      related to exogenous stressors exacerbating carnitine deficiency. Most
      importantly, strict compliance with carnitine from birth appears to prevent the
      phenotype.

PMID- 12210325
TI  - Interstitial microdeletion of chromosome 1p in two siblings.
AB  - Two half-siblings are described with what we believe to be the second and third
      cases identified of the microdeletion, del(1)(p32.1p32.3). Both siblings had a
      tethered cord and had mental retardation, but otherwise their phenotypic
      presentations were quite different. The sister had failure to thrive, congenital
      dysplasia of the hip, absent corpus callosum, Chiari I malformation, and
      syringomyelia. The brother experienced neonatal seizures secondary to a
      hemorrhagic stroke. He had an accessory thumb, inguinal hernia, cryptorchidism,
      urinary reflux, and cholelithiasis. Although these children have only delayed
      development in common with the previously reported case, they help to further
      define chromosomal deletions in this area of chromosome 1. As yet, no clear
      phenotypic picture has emerged.

PMID- 12210326
TI  - Mosaic trisomy 9 and lobar holoprosencephaly.
AB  - The main features of trisomy 9 syndrome in mosaic and non-mosaic forms have been
      thoroughly described. Characteristic traits are low-set malformed ears,
      micrognathia, broad nose with bulbous tip, abnormal brain, congenital heart
      defects, abnormal hands and feet, genital abnormalities, and early death. We
      report a case of mosaic trisomy 9 with holoprosencephaly (HPE). The propositi was
      born at 37 weeks, with intra-uterine growth retardation, hypotelorism and single
      nostril, ventricular septal defect, anterior placement of anus, clenched hands
      with thumb adduction and ulnar deviation. Facial anomalies characteristic of
      trisomy 9 included deeply set eyes and short palpebral fissures, flat face with
      maxillary hypoplasia, small mouth, and low-set posteriorly angulated ears.
      Cytogenetic analysis showed mosaic trisomy 9 with 17% trisomic cells. Pathology
      confirmed lobar HPE. In literature, isolated arrhinia, related to the HPE
      spectrum, was reported in one case of mosaic trisomy 9. Our case raises the
      question of the causative role of trisomy 9 in full blown HPE.

PMID- 12210327
TI  - A dominantly inherited malformation syndrome with short stature, upper limb
      anomaly, minor craniofacial anomalies, and absence of TBX5 mutations: report of a
      Thai family.
AB  - We report on a Thai family with dominantly inherited malformation syndrome with
      upper limb anomalies, short stature, quadricuspid aortic valve, and minor
      craniofacial anomalies. The affected individuals comprised a mildly affected
      mother, a moderately affected daughter, and a most severely affected son. The
      daughter and son had short stature. The craniofacial abnormalities comprised
      frontal bossing, hypoplastic nasal bones, depressed nasal bridge, and broad nasal
      alae. The upper limb defects varies among the patients, ranging from radial ray
      defects in the mother through radial and ulnar ray defects with unilateral
      humeral hypoplasia in the daughter to radial ray defects with severe oligodactyly
      and bilateral humeral hypoplasia in the son. All patients in this family had
      hypoplasia of the shoulder girdle and resembled what is observed in many families
      with Holt-Oram syndrome. Moreover, the son showed quadricuspid aortic valve with
      mild aortic regurgitation. However, the present family did not show any mutation
      of the TBX5 gene, a disease-causing gene of Holt-Oram syndrome. The present
      family deserves further investigation on other genes that play a role in the
      development of the upper limbs, particularly of radial rays.

PMID- 12210328
TI  - Partial duplication 4q and deletion 1p36 in monozygotic twins with discordant
      phenotypes.
AB  - We report on monozygotic (MZ) twins with a de novo chromosome abnormality
      consisting of a partial duplication of chromosome 4 (q25-qter) and deletion of
      chromosome 1p36. These infants had dysmorphic facial features and other clinical
      manifestations similar to those described with the previously delineated
      duplication 4q and deletion 1p36 phenotypes and two other reported cases of
      combined partial duplication 4q and deletion 1p36. However, the twins were
      discordant for a number of congenital anomalies. The discordant phenotypes
      described in these genetically identical infants demonstrate that nongenetic
      factors may play a significant role in the phenotypic differences in patients
      with recognized chromosome duplication and deletion syndromes, which are usually
      attributed to the individual genotypic differences in the duplicated and/or
      deleted chromosome segments.

PMID- 12210329
TI  - Genitopatellar syndrome: a recognizable phenotype.
AB  - Genitopatellar syndrome is a newly described condition, subject of a single
      literature report to date. The condition comprises absent patellae, genital and
      renal malformations, joint dislocation, and mental retardation. Recurrence has
      been recorded in two kindreds, consistent with autosomal recessive inheritance.

PMID- 12210330
TI  - Genitopatellar syndrome: delineating the anomalies of female genitalia.
AB  - We report the second female with genitopatellar syndrome, a recently identified
      arthrogryposis syndrome. The salient features include severe mental retardation
      and microcephaly with absence of the corpus callosum, absent/hypoplastic
      patellae, genital anomalies, and hydronephrosis.

PMID- 12210331
TI  - Small familial supernumerary ring chromosome 2: FISH characterization and
      genotype-phenotype correlation.
AB  - A child and his mother were found to be mosaic for a small supernumerary marker
      chromosome (SMC) that was identified and characterized by means of fluorescent in
      situ hybridization. The marker chromosome was derived from the pericentromeric
      region of chromosome 2; the involvement of proximal 2q was determined by YAC
      probes. The proband was referred because of psychotic illness and mild mental
      retardation, whereas his mother presented only minor dysmorphisms. There are only
      a few published reports concerning SMC(2) or proximal 2q trisomy. We reviewed the
      previously reported cases in an attempt to establish genotype-phenotype
      correlations, which are particularly important when SMCs are identified in
      prenatal diagnosis.

PMID- 12210332
TI  - TCOF1 mutations excluded from a role in other first and second branchial arch
      related disorders.

PMID- 12210333
TI  - Genes and translocations involved in POF.
AB  - Changes at a single autosomal locus and many X-linked loci have been implicated
      in women with gonadal dysgenesis [premature ovarian failure (POF) with deficits
      in ovarian follicles]. For the chromosome 3 locus, a forkhead transcription
      factor gene (FOXL2) has been identified, in which lesions result in decreased
      follicles by haploinsufficiency. In contrast, sporadic X; autosomal
      translocations are distributed at many points on the X, but concentrate in a
      critical region on Xq. The association of the breakpoints with genes involved in
      ovarian function is thus far weak (in four analyzed cases) and has not been
      related to pathology in other POF patients. While many more translocations can be
      analyzed in detail as the human genome sequence is refined, it remains possible
      that translocations like X monosomy (Turner syndrome) lead to POF not by
      interrupting specific genes important in ovarian development, but by causing
      aberrations in pairing or X-inactivation during folliculogenesis. It is noted
      that the critical region has unusual features, neighboring the X-inactivation
      center and including an 18 Mb region of very low recombination. These suggest
      that chromosome dynamics in the region may be sensitive to structural changes,
      and when modified by translocations might provoke apoptosis at meiotic
      checkpoints. Choices among models for the etiology of POF should be feasible
      based on studies of ovarian follicle development and attrition in mouse models.
      Studies would prominently include gene expression profiling of developmental
      specific pathways in nascent ovaries with controlled levels of Foxl2 and
      interacting proteins, or with defined changes in the X chromosome.

PMID- 12210334
TI  - O patient, where art thou?

PMID- 12210335
TI  - Fifteen-year-old boy with stress-induced arrhythmia and sudden death.

PMID- 12210336
TI  - Don't use the term "amyoplasia" loosely.

PMID- 12210337
TI  - Further delineation of cardiac abnormalities in Costello syndrome.
AB  - We review the cardiac abnormalities in 94 patients (27 new, 67 literature) with
      Costello syndrome, an increasingly recognized syndrome consisting of increased
      birth weight, postnatal growth retardation, and distinctive facial, skin, and
      musculoskeletal features (MIM 218040). A cardiac abnormality was found in 59
      (63%) patients, with each of three categories occurring in approximately one
      third of patients. A cardiovascular malformation (CVM) was noted in 30%,
      typically pulmonic stenosis (46% of those with a CVM). Cardiac hypertrophy was
      reported in 34%, which involved the left ventricle in 50% and was usually
      consistent with classic hypertrophic cardiomyopathy (HCM). A variety of rhythm
      disturbances were reported in 33%. Most (74%) were atrial tachycardia that was
      reported as supraventricular, chaotic, multifocal, or ectopic. Of 31 patients
      with a rhythm abnormality, 22 (68%) had an additional abnormality, i.e., CVM (4),
      cardiac hypertrophy (12), or both (6). Nine patients had isolated dysrhythmia,
      five (56%) of whom died. All of the 12 (13%) patients who died had a cardiac
      abnormality. One patient died of embryonal rhabdomyosarcoma, but in the
      remainder, a cardiac cause of death could not be disproved. All patients with
      Costello syndrome need a baseline cardiology evaluation with echocardiography and
      Holter monitoring. Additional prospective evaluations, even in patients without
      apparent cardiac abnormalities, would be prudent, although data are insufficient
      to propose a specific schedule.

PMID- 12210338
TI  - Facial appearance in persistent hyperinsulinemic hypoglycemia.
AB  - Persistent hyperinsulinism is the most common cause of recurrent hypoglycemia in
      infancy because of inappropriate oversecretion of insulin by the pancreas.
      Pancreatic lesions can be either focal or diffuse, and they have distinct
      molecular bases. We have studied the facial features in 17 unrelated patients
      presenting with neonatal (n = 8) or infancy-onset (n = 9) hyperinsulinism.
      Hyperinsulinism was related to focal adenomatous hyperplasia (n = 7), diffuse
      hyperinsulinism (n = 5), non-operated hyperinsulinism (n = 2), and
      hyperinsulinism with hyperammonemia (n = 3). SUR1 or Kir6.2 mutations were found
      in six of seven focal adenomatous hyperplasia and three of five diffuse
      hyperinsulinism. A loss of the maternal allele from chromosome 11p15 in the
      lesion was found in all focal adenomatous hyperplasia. GLUD1 mutations were found
      in all patients with hyperammonemia. Large birth weight (mean > 3,800 g) was
      consistently observed (11/17) but protruding tongue, exomphalos, or visceromegaly
      were never noted and Wiedemann-Beckwith syndrome could always be ruled out. All
      patients presented with high forehead, small nasal tip, and short columella
      giving the impression that the nose is large and bulbous, smooth philtrum, and
      thin upper lip. A square appearance to the face was more obvious in younger
      patients. These specific facial features, observed in patients with
      hyperinsulinism of various molecular mechanisms, could be the consequence of
      fetal intoxication by insulin. However, to date, facial anomalies have not been
      noted in infants of diabetic mothers and inversely, malformations that are
      commonly reported in infants of diabetic mothers were not present in our
      hyperinsulinemic patients.

PMID- 12210339
TI  - Parental origin of normal X chromosomes in Turner syndrome patients with various
      karyotypes: implications for the mechanism leading to generation of a 45,X
      karyotype.
AB  - The parental origin of the X chromosome of 45,X females has been the subject of
      many studies, and most of them have shown that the majority (60-80%) of the X
      chromosomes are maternal in origin. However, studies on the parental origin of
      normal X chromosomes are relatively limited for Turner syndrome (TS) females with
      sex chromosome aberrations. In this study, we used PCR-based typing of highly
      polymorphic markers and an assay of methylation status of the androgen receptor
      gene to determine the parental origin of normal X chromosomes in 50 unbiased TS
      females with a variety of karyotypes. Our results showed a higher paternal
      meiotic error rate leading to the generation of abnormal sex chromosomes,
      especially in the case of del(Xp) and abnormal Y chromosomes. Isochromosome Xq
      and ring/marker X chromosomes, on the other hand, were equally likely the result
      of both maternal and paternal meiotic errors. A thorough review of previous
      results, together with our data suggests, that the majority of TS karyotype are
      caused by paternal meiotic errors that generate abnormal sex chromosomes, and
      that most 45,X cells are generated by mitotic loss of these abnormal sex
      chromosomes, resulting in maternal X dominance in these cells.

PMID- 12210340
TI  - Dendritic spine and dendritic field characteristics of layer V pyramidal neurons
      in the visual cortex of fragile-X knockout mice.
AB  - Fragile-X syndrome is a common form of mental retardation resulting from the
      inability to produce the fragile-X mental retardation protein. The specific
      function of this protein is unknown; however, it has been proposed to play a role
      in developmental synaptic plasticity. Examination of human brain autopsy material
      has shown that fragile-X patients exhibit abnormalities in dendritic spine
      structure and number, suggesting a failure of normal developmental dendritic
      spine maturation and pruning in this syndrome. Similar results using a knockout
      mouse model have previously been described; however, it was noted in retrospect
      that the mice used in that study may have carried a mutation for retinal
      degeneration, which may have affected cell morphology in the visual cortex of
      those animals. In this study, dendritic spines on layer V pyramidal cells of
      visual cortices, taken from fragile-X knockout and wild-type control mice without
      the retinal degeneration mutation and stained using the Golgi-Cox method, were
      investigated for comparison with the human condition. Quantitative analyses of
      the lengths, morphologies, and numbers of dendritic spines, as well as amount of
      dendritic arbor and dendritic branching complexity, were conducted. The fragile-X
      mice exhibited significantly more long dendritic spines and significantly fewer
      short dendritic spines than control mice. Similarly, fragile-X mice exhibited
      significantly more dendritic spines with an immature-like morphology and
      significantly fewer with a more mature type morphology. However, unlike the human
      condition, fragile-X mice did not exhibit statistically significant dendritic
      spine density differences from controls. Fragile-X mice also did not demonstrate
      any significant differences from controls in dendritic tree complexity or
      dendritic arbor. Long dendritic spines with immature morphologies are
      characteristic of early development or a lack of sensory experience. These
      results are similar to those found in the human condition and further support a
      role for the fragile-X mental retardation protein specifically in normal
      dendritic spine developmental processes. They also support the validity of these
      mice as a model of fragile-X syndrome.

PMID- 12210342
TI  - Further evidence for a fourth gene causing X-linked pure spastic paraplegia.
AB  - X-linked hereditary spastic paraplegias (HSPs) present with two distinct
      phenotypes: pure and complicated. The pure form is characterized by slowly
      progressive weakness and spasticity of the lower limbs, whereas the complicated
      forms have additional features (optic neuropathy, retinopathy, extrapyramidal
      disturbance, dementia, epilepsy, ataxia, ichthyosis, mental retardation, and
      deafness). Three X-linked loci have been identified for the complicated HSP,
      while mutations in the proteolipid gene (PLP) (locus SPG2) were implicated in
      both pure and complicated forms. The absence of identified mutations in the PLP
      gene in families with both complicated and pure HSP, linked to the SPG2 locus,
      suggests the existence of another gene in close proximity. We had previously
      reported a large pedigree with an X-linked form of pure HSP affecting 24 males
      [Zatz et al., 1976: J Med Genet 13:217-222]. Here, we present the results of
      linkage analysis in 19 members of this Brazilian family with markers in or near
      the PLP locus. Positive LOD scores were obtained with markers at the PLP locus
      (Zmax = 2.41 at Theta = 0); however, no mutation was found in the coding region
      of PLP, the intron-exon boundaries, or part of the promoter region. The
      possibility of a duplication of the PLP gene was also excluded. These results
      suggest either that there is another X-linked gene in close proximity to the PLP
      gene or that a novel mutation in the noncoding regions of the PLP gene may cause
      the disease in this family.

PMID- 12210341
TI  - Genetic counseling in hereditary breast/ovarian cancer in Israel: psychosocial
      impact and retention of genetic information.
AB  - Genetic counseling for individuals at high risk for developing breast and ovarian
      cancer (oncogenetic counseling) involves evaluation of cancer risk, psychological
      assessment, and genetic testing for germline mutations in BRCA1/BRCA2 genes. The
      long-term psychosocial impact of oncogenetic counseling on consultees and the
      retention of oncogenetic information are uncertain. We retrospectively
      interviewed 155 women who underwent oncogenetic counseling in a single medical
      center in Israel in 1996 (N = 50) and 1998 (N = 105). There were 29 (18.7%)
      BRCA1/BRCA2 mutation carriers and 126 non-carriers; 58 (37.4%) had a past or
      present history of cancer, and 97 (62.6%) were first-degree relatives within
      breast/ovarian cancer families. A questionnaire evaluating self-reported distress
      and anxiety symptoms before and after counseling, as well as the retention of
      relevant information (e.g., individual and offspring cancer risk, early detection
      schemes), one and three years after the initial consultation was administered.
      Overall, oncogenetic counseling had a minimal effect on anxiety-related symptoms.
      Mutation carriers reported anxiety-associated symptoms, such as sleeplessness and
      "bad mood", more frequently than non-carriers following oncogenetic counseling.
      As expected, 61.8% of carriers and only 30% of non-carriers accurately remembered
      the personal and offspring cancer risk and preventive and early detection
      schemes. We conclude that although there seemed to be slight worsening of anxiety
      related symptoms following oncogenetic counseling in BRCA1/BRCA2 mutation
      carriers, these symptoms were minimal and did not affect everyday life
      activities. In addition, there is an ongoing need to emphasize oncogenetic
      information to high-risk individuals.

PMID- 12210343
TI  - Evaluation of multiple presenilin 2 SNPs for association with early-onset
      sporadic Alzheimer disease.
AB  - The presenilin genes encode proteins that modify, mediate, or perform similar
      functions to gamma-secretase, the enzyme responsible for converting amyloid beta
      precursor protein (APP) into beta-amyloid. Mutations in the presenilin genes
      cause an increased production of Abeta42, the aberrant form of beta-amyloid found
      in the neural plaques of Alzheimer disease patients. Previously reported
      association studies of presenilin 2 (PSEN2) polymorphisms with early-onset
      Alzheimer disease (EOAD) have produced contradictory results. In an effort to
      resolve these differences, we tested eight single nucleotide polymorphisms in and
      around the 3' region of the PSEN2 gene for association with EOAD. An initial set
      of Scottish EOAD cases (n = 121) and controls (n = 152) was screened using the
      genotyping method dynamic allele-specific hybridization (DASH). No significant
      differences were seen between allele or genotype frequencies of cases and
      controls. However, when conditioned on the risk allele (epsilon 4) APOE, three
      polymorphisms showed allelic association with a P value below 0.05. These same
      polymorphisms were in near 100% linkage disequilibrium with each other (P < 5 x
      10(-5)), and in each, one of the homozygous genotypes was absent in controls but
      present in the cases. Replication in an independent set of Scottish EOAD cases (n
      = 84) and controls (n = 173) did not confirm this finding. From this study we
      find no evidence to suggest that variations in the PSEN2 gene pose as major risk
      factors for sporadic EOAD.

PMID- 12210344
TI  - Balanced X chromosome inactivation patterns in the Rett syndrome brain.
AB  - In Rett syndrome (RTT), an X-linked disorder essentially limited to females,
      neurological development goes awry. Causing this disarray in neuronal function is
      a mutated form of a protein known as methyl-CpG-binding protein 2 (MeCP2).
      Because the MECP2 gene is subject to X chromosome inactivation (XCI) in females,
      a number of studies have addressed whether the percentage of cells inactivating
      the normal vs. mutant chromosome in heterozygous females influences the
      phenotypic outcome of MECP2 mutations. Because most of these studies measured XCI
      in peripheral blood, however, interpretation of the results requires the
      assumption that XCI patterns in blood are representative of those in the brain,
      the primarily affected tissue. Here, we have analyzed the MECP2 sequence and XCI
      status in 13 brains of RTT patients. Mutations were identified in nine of the
      cases, with eight of these representing C to T transitions at CpG dinucleotides,
      and one being a novel frameshift mutation (765delA). Patterns of XCI were
      balanced in 10 of 10 cases for which the assay was informative. As previous
      studies have shown that a majority of RTT patients have balanced XCI patterns in
      peripheral blood, our results suggest that the pattern in blood is an accurate
      indicator of XCI patterns in the brain for a majority of cases, but there are
      some notable exceptions that this study may help explain. Given the correlation
      between balanced XCI and classic RTT, these results suggest that a certain
      percentage of neurons expressing the mutant MECP2 gene may be required for RTT to
      become manifest.

PMID- 12210346
TI  - Four cases with hypoplastic thumbs and encephaloceles.
AB  - We report on four infants with hypoplastic thumbs and occipital encephaloceles.
      None had either a chromosome abnormality or a family history of any major
      malformation. The literature and database were searched intensively. No similar
      cases were reported previously, suggesting that the constellations might
      represent a new genetic syndrome.

PMID- 12210345
TI  - Omodysplasia: an affected mother and son.
AB  - We describe a second family with mother to son transmission of omodysplasia, a
      rare skeletal dysplasia characterized by shortened humeri, shortened first
      metacarpals and craniofacial dysmorphism. The mother in this family had been
      diagnosed previously with Robinow syndrome; subsequently, her diagnosis was
      reclassified. Her pregnancy was closely monitored antenatally with serial
      ultrasound examinations. Delayed ossification of the humerus was noted
      prenatally. Her son had ambiguous genitalia and similar skeletal manifestations
      as his mother. A comparison to other known and suspected cases of dominant
      omodysplasia is presented. Our observations confirm the existence of a dominant
      variant of omodysplasia, document genital hypoplasia as an important feature of
      this syndrome in males and highlight the need to differentiate this entity from
      Robinow syndrome.

PMID- 12210347
TI  - Familial Axenfeld-Rieger anomaly, cardiac malformations, and sensorineural
      hearing loss: a provisionally unique genetic syndrome?
AB  - Axenfeld-Rieger anomaly (ARA) is an autosomal dominant disorder of the anterior
      chamber of the eye that includes a prominent and anteriorly displaced Schwalbe
      line and an iridocorneal synechiae, and is associated with iris hypoplasia,
      corectopia, and hole formation. Extraocular developmental abnormalities,
      especially of the teeth, facial bones, and periumbilical skin, have also been
      reported with ARA, in the context of the so-called Axenfeld-Rieger syndrome
      (ARS). Genetic heterogeneity exists, as ARA maps to chromosome 6p25, whereas ARS
      can be linked to both chromosome 4q25 and chromosome 13q14. Here we describe a
      new family in which ARA is associated with cardiac malformations and
      sensorineural hearing loss. No abnormalities of the teeth, facial bone, or
      periumbilical skin, which are considered of paramount importance in the diagnosis
      of ARS, were observed in our patients. Genetic studies will clarify if these
      patients represent a unique phenotypic expression of ARS or constitute the
      clinical presentation of a new genetic syndrome.

PMID- 12210348
TI  - Wolcott-Rallison syndrome in two siblings with isolated central hypothyroidism.
AB  - Two sibs with an infantile onset of hyperglycemia, recurrent hepatitis, renal
      insufficiency, developmental delay, and skeletal epiphyseal dysplasia are
      described. Clinical presentation and radiological features are suggestive of
      Wolcott-Rallison syndrome, a rare autosomal recessive disease. In both of our
      cases we found evidence of central hypothyroidism, which appears to be an
      associated feature of this syndrome. Hypothyroidism should be suspected and
      screened for in all cases of Wolcott-Rallison syndrome.

PMID- 12210349
TI  - Familial childhood onset neuropathy and cirrhosis with the 4977bp mitochondrial
      DNA deletion.
AB  - The common 4977 base pair mitochondrial deletion has been identified in
      association with a number of distinct clinical phenotypes. These include the
      Kearns-Sayre syndrome, the Pearson marrow-pancreas syndrome, and chronic
      progressive external ophthalmoplegia. We report the clinical and pathological
      findings in two siblings in whom the 4977 base pair mitochondrial DNA deletion
      was identified in muscle-derived mitochondrial DNA. One sibling manifested early
      onset liver and renal failure, and both developed prominent peripheral
      sensorimotor neuropathy. These clinical findings have not been previously
      described in association with the 4977bp mtDNA deletion and thus represent a
      further expansion of the spectrum of mitochondrial disease.

PMID- 12210350
TI  - Cobalamin disorder Cbl-C presenting with late-onset thrombotic microangiopathy.
AB  - Two siblings, a boy age 12 and his sister age 4 years, presented with proteinuria
      and hematuria, hypertension, and chronic hemolytic anemia. At age 13 years, the
      boy developed an episode of severe hypertensive encephalopathy and transient
      renal failure. Both children are attending normal school, have no neurologic
      symptoms, and only minimal pigmentary retinal abnormalities. Renal biopsy showed
      a chronic thrombotic microangiopathic nephropathy. Both patients had
      hyperhomocysteinemia and mild methylmalonic aciduria. Fibroblasts showed
      decreased cobalamin uptake, reduced methyl- and adenosyl-cobalamin formation, and
      deficient incorporation of formate and propionate, compatible with the Cbl-C
      complementation group, but milder than that found in cells from most patients.
      Both patients and their father carry a balanced reciprocal translocation.
      Parenteral hydroxycobalamin treatment reduced the homocysteine levels, and
      methylmalonic acid disappeared. Increasing the dosage of hydroxycobalamin from 1
      to 2.5, then 5 mg daily together with betaine, further reduced homocysteine
      levels (boy from 118 to 23 microM and girl from 59 to 14 microM). With this
      treatment, hemolysis has stopped, hematuria has disappeared, proteinuria has
      almost normalized, and creatinine clearance has been stable. Investigations for
      chronic thrombotic microangiopathy should include testing for this unusual but
      treatable disorder, regardless of age of presentation.

PMID- 12210351
TI  - A 45,X sterile male with Yp disguised as 21p.
AB  - An azoospermic male was found to have, by means of banding techniques, a 45,X
      karyotype including a monocentric chromosome 21 with an euchromatic short arm
      that looked similar to Yp. This rearranged chromosome was further characterized
      by FISH with a whole Y chromosome paint and the alphoid repeats DYZ3 and
      D13Z1/D21Z1; the former probe gave a positive signal onto such a peculiar arm
      without spreading into the long arm, whereas the alphoid repeats revealed an
      apparent compound centromere with Y- and 21-sequences. Therefore, an unbalanced
      Y;21 whole arm translocation was concluded and the karyotype written as 45,X.ish
      der(Y;21)(p10;q10)(wcpY+,DYZ3+,D13Z1/D21Z1+). This patient represents the first
      case of a Y;21 translocation in an apparent 45,X male, constitutes the fifth
      instance of a 45,X sterile male, and conforms to previously established karyotype
      phenotype correlations.

PMID- 12210352
TI  - Further case of Cantu syndrome: exclusion of cryptic subtelomeric chromosome
      aberrations.
AB  - Cantu syndrome consists of hypertrichosis, osteochondrodysplasia, and
      cardiomegaly, and has been reported in 18 patients to date. We report an infant
      with Cantu syndrome. In addition to typical findings, he had relatively mild
      radiological and cardiological manifestations. Previously undescribed findings
      included pyloric stenosis and elevated alkaline phosphatase levels. Brain scans
      showed bilateral calcification of the Arteriae thalamostriatae and widening of
      the outer liquor spaces and lateral ventricles. Because the propositus is the
      youngest patient reported to date, our findings refine the clinical spectrum of
      Cantu syndrome in neonates and young infants. The etiology and mode of
      inheritance of Cantu syndrome are unknown. Most cases are sporadic.
      Microdeletions have been discussed as a possible cause of Cantu syndrome.
      Recently, several syndromes with multiple congenital anomalies and mental
      retardation have been shown to be caused by subtelomeric chromosome aberrations.
      We excluded the presence of a cryptic subtelomeric chromosome anomaly in our
      patient by fluorescence in situ hybridization (FISH) screening with locus
      specific probes.

PMID- 12210353
TI  - Posterior urethral valves and mirror image anomalies in monozygotic twins.
AB  - Monozygotic (MZ) twins with both posterior urethral valves (PUV) and additional
      mirror image malformations are described. This association suggests that an early
      embryonic event may lead to MZ twinning, PUV, and mirror image anomalies.

PMID- 12210354
TI  - Revaluation twenty-three years later of a supernumerary derivative chromosome 9.

PMID- 12210355
TI  - Report of 46,XX/46,XY/47,XXY/48,XXYY mosaicism in an adult phenotypic male.

PMID- 12210356
TI  - Studies with His475Tyr glutamate carboxipeptidase II polymorphism and neural tube
      defects.

PMID- 12210357
TI  - Pulmonary alveolar microlithiasis: clinical features, evolution of the phenotype,
      and review of the literature.
AB  - Pulmonary alveolar microlithiasis (PAM) (MIM 265100) is a rare, autosomal
      recessive pneumopathy characterized by intra-alveolar formation and accumulation
      of tiny, roundish corpuscles called "microliths". The name "alveolar
      microlithiasis" was first used by Puhr in 1933; since then, several reports have
      appeared, and over 300 individuals with this condition have been reported. We
      have reviewed the PAM cases in the literature in light of personal experience,
      focusing on medical implications, disease diagnosis and progression over time,
      familial predisposition, and geographical and sex distribution. This study
      confirms autosomal recessive inheritance and does not support the role of other,
      non-genetic, factors in the pathogenesis of PAM.

PMID- 12210358
TI  - Some pitfalls of segregation analysis of complex traits.

PMID- 12210359
TI  - Somatic mosaicism and variable expression of Townes-Brocks syndrome.

PMID- 12210360
TI  - Genetic disorders of neuromuscular ion channels.
AB  - Ion channels are complex proteins that span the lipid bilayer of the cell
      membrane, where they orchestrate the electrical signals necessary for normal
      function of the central nervous system, peripheral nerve, and both skeletal and
      cardiac muscle. The role of ion channel defects in the pathogenesis of numerous
      disorders, many of them neuromuscular, has become increasingly apparent over the
      last decade. Progress in molecular biology has allowed cloning and expression of
      genes that encode channel proteins, while comparable advances in biophysics,
      including patch-clamp electrophysiology and related techniques, have made the
      study of expressed proteins at the level of single channel molecules possible.
      Understanding the molecular basis of ion channel function and dysfunction will
      facilitate both the accurate classification of these disorders and the rational
      development of specific therapeutic interventions. This review encompasses
      clinical, genetic, and pathophysiological aspects of ion channels disorders,
      focusing mainly on those with neuromuscular manifestations.

PMID- 12210361
TI  - Neuronal control and monitoring of initiation of movements.
AB  - The prerequisite for behavioral self-control is the ability to initiate actions
      and to cancel planned actions. A rational choice about which action to initiate
      or to withhold must be informed by the consequences of prior actions. The
      neuronal correlates of these processes have been studied with the countermanding
      paradigm. This task requires subjects to withhold planned movements in response
      to an imperative stop signal, which they can do with varying success. By
      recording the activity of single neurons in different parts of the frontal cortex
      of macaque monkeys performing this task, signals that are sufficient for
      controlling the initiation and inhibition of movements and other signals that
      evaluate the consequences of these movements have been identified.

PMID- 12210362
TI  - Intrapartum maternal lumbosacral plexopathy.
AB  - There are many conflicting theories regarding the mechanism and prognosis of
      acute foot drop during labor. We report seven women who had arrested labor and
      foot drop. Six had short stature and one had a large newborn. All had weakness of
      ankle dorsiflexion, eversion, and inversion, and sensory loss in the L-5
      dermatome. Superficial peroneal sensory nerve action potentials (SNAPs) were
      small or absent in six patients, and the sural SNAP was attenuated in one.
      Peroneal compound muscle action potential (CMAP) amplitude (recording from
      extensor digitorum brevis) was low in five, whereas the tibial CMAP was normal in
      all patients. Peroneal CMAP amplitude (recording from the tibialis anterior) was
      normal in three and small in three. Needle electromyography revealed decreased
      recruitment and fibrillation potentials in L-5-innervated muscles, mostly below
      the knee. We conclude that intrapartum foot drop occurs mostly in short women and
      is caused by lumbosacral trunk compression by the fetal head at the pelvic brim.
      The primary pathology is predominantly demyelination and recovery is complete in
      up to 5 months.

PMID- 12210363
TI  - Bimodal dose-dependence of FK506 on the rate of axonal regeneration in mouse
      peripheral nerve.
AB  - FK506 has been shown to enhance the rate of axonal regeneration after peripheral
      nerve lesions. However, quite variable doses of FK506 have been used in different
      animal studies. We examined the dose-dependence of FK506 on the rate of axonal
      regeneration after crush lesion of the mouse sciatic nerve. Mice received daily
      subcutaneous injections of FK506 at 0.2, 0.5, 1, 2, 5, or 10 mg/kg for 7 days
      after lesioning. A control group was injected with saline. The distance that
      regenerative axons advanced from the crush site was measured by the pinch test at
      2, 4, and 7 days. Regenerating axons reached greater mean distances in all FK506
      treated groups compared to the control group. The fastest regeneration rate was
      found at 5 mg/kg (12% increase over controls), although the 0.2 and 2 mg/kg doses
      achieved similar regeneration rates. In contrast, intermediate doses (0.5 and 1
      mg/kg) and a higher dose (10 mg/kg) were not different from controls. Calcitonin
      gene-related peptide immunohistochemical labeling of regenerating axons yielded
      similar results to those found with the pinch test. Based on our finding of a
      double peak in the dose-response for FK506, it is hypothesized that at least two
      mechanisms of action (perhaps corresponding to distinct functional binding sites)
      are evoked at different concentrations of the drug to accelerate nerve
      regeneration. These results have clinical implications for the pharmacological
      treatment of nerve injuries while avoiding immunosuppressive effects and for the
      design of related drugs with more specific activities.

PMID- 12210364
TI  - Ultrasound therapy facilitates the recovery of acute pressure-induced conduction
      block of the median nerve in rabbits.
AB  - Though the use of ultrasound for the treatment of carpal tunnel syndrome (CTS) or
      compression neuropathy has been described, its effect remains controversial. A
      test model of acute CTS was developed using rabbits. Acute median nerve
      compression was induced by the infusion of saline into the carpal tunnel under
      general anesthesia to elevate the intracarpal pressure. A reduction in the
      compound muscle action potential (CMAP) amplitude of the abductor pollicis was
      noted after intracarpal pressure increased. To investigate the efficacy of
      ultrasound in acute CTS, rabbits with acute median nerve compression were divided
      into 3 groups (10 each) and ultrasound was applied at different intensities to
      each group as follows: 1.5 W/cm(2) to group 1; 0.2 W/cm(2) to group 2; 0.0
      W/cm(2) (sham) to group 3. A total of 10 treatment sessions were given over a
      period of 2 weeks. Following ultrasound application, the CMAP amplitudes showed
      significant improvement in group 1 compared to the other two groups (P < 0.05),
      indicating facilitated recovery from acute CTS in this pressure-induced median
      nerve compression rabbit model. The benefits of ultrasound application in a
      clinical setting must be verified by further clinical trials.

PMID- 12210365
TI  - Refinements in nerve to muscle neurotization.
AB  - A modified surgical technique is introduced, enabling restoration of muscle
      function with direct muscular neurotization. Reliable clinical outcomes result
      from this technique. We report on a series of 10 patients in whom the supplying
      motor nerve had been lost at the level of the neuromuscular junction as the
      result of trauma or tumor resection. Our modification of the operative technique
      ensures a wide distribution of nerve fibers throughout the remaining muscle
      tissue and produces a mean motor recovery of M4 after a period of 1 to 2 years.

PMID- 12210366
TI  - MMG and EMG responses during fatiguing isokinetic muscle contractions at
      different velocities.
AB  - The purpose of this study was to determine mechanomyographic (MMG) and
      electromyographic (EMG) responses of the superficial quadriceps muscles during
      repeated isokinetic contractions in order to provide information about motor
      control strategies during such activity, and to assess uniformity in mechanical
      activity (MMG) between the investigated muscles. Ten adults performed 50 maximal
      concentric muscle contractions at three randomly selected contraction velocities
      (60, 180, and 300 degrees.s(-1)) on different days. Surface electrodes and an MMG
      sensor were placed on the vastus lateralis (VL), rectus femoris (RF), and vastus
      medialis (VM). EMG and MMG amplitude and peak torque (PT) were calculated for
      each contraction, normalized, and averaged across all subjects. The results
      demonstrated that MMG amplitude more closely tracked the fatigue-induced decline
      in torque production at each velocity than did EMG amplitude. This indicates that
      MMG amplitude may be useful for estimating force production during fatiguing
      dynamic contractions when a direct measure is not available, such as during
      certain rehabilitative exercises. MMG amplitude responses of the VL, RF, and VM
      were not uniform for each velocity or across velocities, indicating that it may
      be possible to detect the individual contribution of each muscle to force
      production during repeated dynamic contractions. Therefore, MMG amplitude may be
      clinically useful for detecting abnormal force contributions of individual
      muscles during dynamic contractions, and determining whether various treatments
      are successful at correcting such abnormalities.

PMID- 12210367
TI  - Reflex effects of induced muscle contraction in normal and spinal cord injured
      subjects.
AB  - The modulation of the soleus H reflex in response to functional electrical
      stimulation (FES) of the rectus femoris (RF) muscle and its overlying skin was
      examined in 11 normal adults and 6 patients with a clinically defined complete
      spinal cord injury (SCI). Stimulation of RF at twice motor threshold (MT)
      resulted in a long-lasting (>1,000 ms) and significant reduction (50-70% of
      control) in the size of the soleus H reflex in all normal subjects tested. For
      five of the SCI subjects, 2MT stimulation of RF induced a 55-60% reduction in the
      soleus H reflex that was also long-lasting (>160 ms). In the remaining SCI
      subject, 2MT stimulation resulted in an initial period of significant H-reflex
      facilitation (0-14 ms) that was followed by a longer-lasting inhibition
      commencing 60 ms after the cessation of the conditioning stimulation. Decreasing
      the strength of stimulation to below that required to generate a clear
      contraction in RF resulted in mixed facilitatory and inhibitory actions that were
      subject dependent. The changes in H-reflex excitability resulting from FES
      highlight the potential use of FES in the management of hypertonicity in SCI but
      also suggest that the central actions of FES need to be considered when FES gait
      restoration programs are designed.

PMID- 12210368
TI  - Apoptosis and apoptosis-related proteins in thyroid myopathies.
AB  - DNA fragmentation and apoptosis-related proteins have been investigated in
      thyroid cells and there is evidence that Fas-mediated apoptosis is inhibited by
      thyroid stimulating hormone (TSH). We investigated DNA fragmentation by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and Bcl-2
      and Fas antigen expression by immunocytochemistry in skeletal muscles from 12
      patients with hypothyroid myopathy and 5 patients with hyperthyroid myopathy. The
      finding of very few TUNEL-positive muscle fibers in both conditions suggests that
      apoptosis does not play a role in the pathogenesis of thyroid myopathies. Bcl-2
      expression increased significantly in hypothyroid myopathy, correlating with high
      serum TSH levels, and not with either triiodothyronine (T3) or thyroxine (T4)
      serum levels. By contrast, Fas antigen was overexpressed in hyperthyroid
      myopathy, correlating with low TSH levels. These findings suggest an anti
      apoptotic role for TSH itself in skeletal muscle.

PMID- 12210369
TI  - Predictive power of motor unit potential parameters in anal sphincter
      electromyography.
AB  - The diagnostic utility of motor unit potential (MUP) parameters is usually based
      exclusively on their diagnostic sensitivity, disregarding specificity. In the
      present study, advanced statistical methods were used to determine MUP parameters
      with the highest predictive power for the separation of neuropathic and normal
      external anal sphincter (EAS) muscles. Using multi-MUP analysis, 3,720 MUPs from
      138 muscles of 52 patients with cauda equina lesion and 2,526 from 112 muscles of
      64 controls were obtained. Only two principal components (PCs), which put weight
      on the MUP area and amplitude, were needed to explain all the data variability.
      On logistic and probit regression analyses, MUP area, duration, and number of
      turns gave results identical to all MUP parameters. Our results suggest that only
      these three MUP parameters are needed, and that they are as effective as PCs, in
      MUP analysis of chronic neuropathic EAS muscles. Reduced number of MUP parameters
      is expected to simplify MUP analysis and increase its specificity.

PMID- 12210370
TI  - Comparison of neuromuscular blockade and recovery with botulinum toxins A and F.
AB  - Intramuscular injection of botulinum toxin A is used to treat focal dystonias.
      Because immunoresistance has been documented in some patients, other molecular
      forms of the toxin have been evaluated clinically. The present investigation
      compared the time course and extent of neuromuscular blockade and recovery of
      botulinum toxin types A and F using an electromyographic monitoring system
      implanted in the rat hindlimb. For a given dose, the degree and duration of
      blockade was more complete with type A toxin. Delayed onset of recovery in
      animals that received high doses of type A toxin allowed time for denervative
      changes to prevent a full return to baseline, as confirmed histologically.
      Conversely, animals receiving type F toxin fully recovered within 30 days at all
      dose levels. The rapid recovery with type F toxin suggested that neuromuscular
      transmission was restored via the original terminals rather than through
      functional collateral sprouting. The reversible nature of blockade with this
      molecular species puts in question its future clinical utility.

PMID- 12210371
TI  - Mechanical properties of the electrically silent adult rat soleus muscle.
AB  - The isometric and isotonic in situ mechanical properties of the soleus muscle of
      adult female rats were determined after 60 days of inactivity induced by spinal
      cord isolation (SI). Compared to control, the absolute muscle mass, physiological
      cross-sectional area, and maximum tetanic tension of the soleus in SI rats were
      reduced by 69%, 66%, and 77%, respectively. Isometric twitch time-to-peak-tension
      and half-relaxation times were 41% and 60% shorter in SI than control rats. The
      maximum velocity of shortening (mm/s), as determined using the afterloaded
      technique, was 66% faster in SI than control rats, whereas unloaded shortening
      velocity was similar in the two groups (9% faster in SI rats). Peak power was 48%
      lower in SI than control rats. The SI soleus was 39% more fatigable than control.
      Thus, the soleus became a smaller, faster, and more fatigable muscle following 60
      days of inactivity. In general, the results indicate that the adaptations are of
      a lesser magnitude than those reported previously following denervation for the
      same duration. These data provide a baseline for future efforts to experimentally
      define the mechanisms of neurally mediated, but activity-independent, regulation
      of the mechanical properties of the rat soleus muscle.

PMID- 12210372
TI  - Sensory-predominant, painful, idiopathic neuropathy: inflammatory changes in
      sural nerves.
AB  - Sensory-predominant, painful, idiopathic neuropathies are a common clinical
      problem. In this retrospective study of 11 patients with such a neuropathy, we
      found axonal loss in 9, with multifocal axonal loss in 4 patients; there were
      large perivascular mononuclear inflammatory infiltrates (>50 cells) in 4 and
      smaller infiltrates (10-20 cells) in 4. These findings suggest that some cases of
      this neuropathy may be due to autoimmune vasculopathy and therefore may respond
      to immunotherapy.

PMID- 12210373
TI  - Clinical variant of familial amyloid polyneuropathy.
AB  - Hereditary amyloidosis with early and prominent peripheral nerve involvement is
      often designated familial amyloid polyneuropathy (FAP). The abnormality usually
      lies in the transthyretin (TTR) gene. We describe a patient with a tyr77 TTR gene
      mutation who presented with sensorimotor polyneuropathy but no other systemic
      symptoms of amyloidosis. This is one of a few documented cases of the tyr77
      mutation in North America. The clinical and electrophysiologic features of this
      unusual cause of sensorimotor polyneuropathy are discussed.

PMID- 12210374
TI  - The medial antebrachial cutaneous nerve: antidromic and orthodromic conduction
      studies.
AB  - Medial antebrachial cutaneous nerve (MABCN) conduction studies were performed
      antidromically and orthodromically in 70 control subjects to determine normal
      values and define the lower limits of normality. The mean sensory action
      potential (SAP) amplitudes were 17.7 and 17.5 microV and the sensory conduction
      velocities were 60 and 61 m/s, respectively, with the antidromic and orthodromic
      techniques. With both techniques, no SAP amplitude was lower than 6 microV. The
      lower limits of normal of the interside amplitude ratio were 1.66 when both
      techniques were used and 2.0 when only one was used.

PMID- 12210375
TI  - Malignant McLeod myopathy.
AB  - Mild myopathy is a common manifestation of the X-linked McLeod
      neuroacanthocytosis syndrome. We present a patient with McLeod syndrome and a
      primarily subclinical myopathy, who developed severe rhabdomyolysis with renal
      insufficiency after a prolonged period of excessive motor restlessness due to an
      agitated psychotic state and a single dose of clozapine. Other possible causes
      for rhabdomyolysis such as prolonged immobility, trauma, hyperthermia,
      generalized seizures, toxin exposure, or metabolic changes were excluded.
      Clinical course was favorable, with persistent slight elevation of serum creatine
      kinase levels caused by the underlying myopathy. Our findings suggest that McLeod
      myopathy is a predisposing factor for severe rhabdomyolysis. This possibly life
      threatening condition should be added to the clinical spectrum of McLeod
      syndrome, and serum creatine kinase levels should be carefully monitored in
      patients with this syndrome, particularly if a hyperkinetic movement disorder is
      present or neuroleptic medication is used.

PMID- 12210377
TI  - Influence of age on nerve conduction.

PMID- 12210379
TI  - Propriospinal transmission of part of the corticospinal excitation in humans.
AB  - In humans a substantial part of corticospinal excitation to upper limb
      motoneurons is mediated through cervical premotoneurons located rostral to
      motoneurons, analogous to the feline system of C3-C4 propriospinal neurons. The
      indirect (disynaptic) component of the corticospinal command passing through the
      propriospinal relay may be updated by the extensive convergence at this level of
      afferent inputs (both excitatory and inhibitory) from the moving limb.
      Propriospinal neurons are potently inhibited by feedback inhibitory interneurons
      facilitated from the motor cortex, and this explains why artificial volleys
      delivered to the pyramidal system by itself have failed to demonstrate this
      indirect corticospinal projection. The strength of this indirect corticospinal
      projection may be estimated in routine practice by the amount of suppression
      elicited by a cutaneous volley on the ongoing electromyogram of extensor carpi
      radialis, and is increased in patients recovering from hemiplegia and in early
      Parkinson's disease.

PMID- 12210380
TI  - Small-fiber neuropathy.
AB  - Small-fiber neuropathy is a common disorder. It is often "idiopathic" and
      typically presents with painful feet in patients over the age of 60. Autoimmune
      mechanisms are often suspected, but rarely identified. Known causes of small
      fiber neuropathy include diabetes mellitus, amyloidosis, toxins, and inherited
      sensory and autonomic neuropathies. Occasionally, small-fiber neuropathy is
      diffuse or multifocal. Depending on the type of small-fiber neuropathy, autonomic
      dysfunction can be significant or subclinical. Diagnosis is made on the basis of
      the clinical features, normal nerve conduction studies, and abnormal specialized
      tests of small-fiber function. These specialized studies include assessment of
      epidermal nerve fiber density as well as sudomotor, quantitative sensory, and
      cardiovagal testing. The sensitivities of these tests range from 59-88%. Each has
      certain advantages and disadvantages, and the tests may be complementary. Unless
      an underlying disease is identified, treatment is usually directed toward
      alleviation of neuropathic pain.

PMID- 12210381
TI  - Patterns of nerve conduction abnormalities in POEMS syndrome.
AB  - Polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS)
      syndrome is a rare cause of demyelinating and axonal neuropathy. POEMS syndrome
      and chronic inflammatory demyelinating polyneuropathy (CIDP) cause peripheral
      nerve demyelination, and the electrodiagnostic findings may therefore be similar,
      but the two disorders are distinct. To elucidate the electrodiagnostic features
      of POEMS syndrome, we reviewed nerve conduction studies of 8 patients, and
      compared their results with those in 42 patients with CIDP. The patients with
      POEMS syndrome showed (1) slowing of nerve conduction that was more predominant
      in the intermediate than distal nerve segments, (2) rare conduction block (6% of
      the tested nerves), and (3) more severe attenuation of compound muscle action
      potentials in the lower than upper limbs. Findings in the CIDP patients were
      characterized by multifocal conduction slowing that was occasionally dominant
      distally, frequent conduction block (44% of tested nerves), and less discrepancy
      between upper and lower limb nerves. The pattern of nerve conduction
      abnormalities differs between these disorders. Recognition of these typical
      patterns may be helpful for early diagnosis of POEMS syndrome.

PMID- 12210382
TI  - Interactions between endogenous nitric oxide and hypoxemia in activation of group
      IV muscle afferents.
AB  - It has previously been shown that both hypoxemia and nitric oxide (NO) synthase
      blockade depress the activation of group IV muscle afferents after muscle
      stimulation (MS). In the present study, we questioned whether hypoxemia exerts a
      specific inhibitory influence, independently from its effects on endogenous NO
      formation. This hypothesis was tested in two groups of anesthetized rabbits in
      which we examined the effects of hypoxemia, and then of subsequent NO synthase
      blockade by N(G)-nitro-L-arginine methyl ester (L-NAME), and vice versa. In each
      protocol, group IV afferent activity was recorded from the resting tibialis
      anterior muscle and after 3-min periods of MS that elicited a significant
      decrease in muscle force. NO synthase blockade in normoxemia suppressed the group
      IV afferent response to MS, and hypoxemia alone significantly reduced the post-MS
      activation of these nerve afferents (+18% vs. +28% in normoxemia). In hypoxemic
      rabbits, further NO synthase blockade abolished the post-MS activation of group
      IV afferents. Moreover, when hypoxemia followed the NO synthase blockade, MS
      significantly reduced the discharge of group IV afferents (-28%). Thus, while
      these muscle afferents are activated after fatiguing muscle contractions when the
      endogenous NO production is present, they are deactivated by hypoxemia when NO
      production is blocked. We conclude that endogenous NO production and hypoxemia
      exert opposite effects on the activation of the group IV afferents. Our data
      anticipate the neuromuscular side effects of treatments using exogenous NO or
      drugs acting on endogenous NO production.

PMID- 12210383
TI  - Diagnostic accuracy of electrodiagnostic testing in the evaluation of weakness.
AB  - Electrodiagnostic testing is often used in the evaluation of patients presenting
      with weakness, but the diagnostic accuracy of the test in this setting is
      unknown. We prospectively identified 100 patients presenting to our
      electromyography (EMG) laboratory with the chief complaint of weakness, and
      compared their referring diagnosis with the electrophysiological diagnosis
      reached after electrodiagnostic testing. We reviewed each patient's medical
      record 9 months after EMG to yield a final diagnosis. Electrodiagnostic testing
      led to a single diagnosis in 79% of the cases; in 31%, this diagnosis was
      unsuspected by the referring clinician. Adequate follow-up was available for 79%
      of the patients. The electrodiagnostic testing resulted in a single, correct
      diagnosis in 73% of the patients and provided more than one possible diagnosis,
      one of which was correct, in an additional 18%, for an overall diagnostic
      accuracy of 91% in this group of patients presenting with weakness.

PMID- 12210384
TI  - GDNF is regulated in an activity-dependent manner in rat skeletal muscle.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is produced by skeletal muscle
      and affects peripheral motor neurons. Elevated expression of GDNF in skeletal
      muscle leads to hyperinnervation of neuromuscular junctions, whereas postnatal
      administration of GDNF causes synaptic remodeling at the neuromuscular junction.
      Studies have demonstrated that altered physical activity causes changes in the
      neuromuscular junction. However, the role played by GDNF in this process in not
      known. The objective of this study was to determine whether changes in
      neuromuscular activity cause altered GDNF content in rat skeletal muscle.
      Following 4 weeks of walk-training on a treadmill, or 2 weeks of hindlimb
      unloading, soleus, gastrocnemius, and pectoralis major were removed and analyzed
      for GDNF content by enzyme-linked immunosorbant assay. Results indicated that
      walk-training is associated with increased GDNF content. Skeletal muscle from
      hindlimb-unloaded animals showed a decrease in GDNF in soleus and gastrocnemius,
      and an increase in pectoralis major. The altered production of GDNF may be
      responsible for activity-dependent remodeling of the neuromuscular junction and
      may aid in recovery from injury and disease.

PMID- 12210385
TI  - Class of nerve fiber involvement in sensory neuropathies: clinical
      characterization and utility of the plantar nerve action potential.
AB  - Precise classification of distal sensory polyneuropathies (SN) according to fiber
      type involvement is desirable for clinical and research purposes. The sural
      sensory response has served as an electrophysiologic gold standard for the
      assessment of large-fiber sensory dysfunction. However, patients labeled as
      having small-fiber sensory neuropathies on the basis of a normal sural response
      frequently have clinical evidence of large-fiber dysfunction. The surface
      recorded medial plantar potential has shown promise as a more sensitive indicator
      of large-fiber sensory dysfunction, but is not widely accepted because of
      concerns about age effects and a lack of large well-controlled studies in SN. We
      have thus correlated clinical type of SN: large-fiber sensory neuropathies
      (LFSN), small-fiber sensory neuropathies (SFSN), and mixed (large- and small
      fiber) sensory neuropathies (MFSN) with sural and medial plantar nerve conduction
      studies in 133 consecutive patients with distal SN and 108 control subjects. A
      combination of stringent clinical characterization and electrophysiologic
      features, especially the surface-recorded medial plantar rather than sural
      potential, was complementary, and permitted a more clear separation of LFSN,
      MFSN, and SFSN than with either approach used alone.

PMID- 12210387
TI  - Effect of moderate dehydration on torque, electromyography, and mechanomyography.
AB  - The purpose of the present investigation was to test the hypotheses that the
      mechanomyographic (MMG) signal would be affected by hydration status due to
      changes in the intra- and extracellular fluid content (which could affect the
      degree of fluid turbulence), changes in the filtering properties of the tissues
      between the MMG sensor and muscle, and changes in torque production that may
      accompany dehydration. Ten subjects (age 22.5 +/- 1.6 years) were tested for
      maximal isometric (MVC), submaximal isometric (25, 50, and 75%MVC), and maximal
      concentric isokinetic muscle strength of the biceps brachii in either a
      euhydrated or dehydrated state while the electromyographic (EMG) and MMG signals
      were recorded. Separate three-way and two-way ANOVAs indicated no change in
      torque, EMG amplitude, EMG mean power frequency (MPF), MMG amplitude, and MMG MPF
      with dehydration. The lack of dehydration effect suggests that MMG may be more
      reflective of the intrinsic contractile processes of a muscle fiber (torque
      production) or the motor control mechanisms (reflected by the EMG) than the
      tissues and fluids surrounding the muscle fiber.

PMID- 12210388
TI  - Conduction slowing in diabetic distal polyneuropathy.
AB  - The pathophysiologic significance of motor conduction slowing observed in
      diabetic distal symmetrical polyneuropathy (DSP) remains controversial. We have
      used multiple linear regression analysis of compound muscle action potential
      (CMAP) amplitude vs. motor conduction velocity (CV) and distal latency (DL) in 57
      patients with diabetic DSP and 34 patients with amyotrophic lateral sclerosis
      (ALS) to determine whether motor conduction slowing in diabetic DSP is due mainly
      to loss of large axons as in ALS or whether there is an additional demyelinative
      component. We found amplitude-dependent slowing of CV and DL in both diabetic DSP
      and ALS in the upper and lower extremities, consistent with a loss of large
      myelinated fibers. However, in diabetic DSP, there was also significant amplitude
      independent slowing in intermediate but not distal nerve segments, supportive of
      an additional demyelinative component. CMAP amplitude vs. CV and DL regression
      analyses using ALS as a control group for relatively pure axon loss may provide
      pathophysiologic information about motor nerves in other neuropathic disorders.

PMID- 12210386
TI  - Reduced thrombomodulin in human peripheral nerve microvasculature.
AB  - Thrombomodulin (TM), a vascular endothelial receptor, terminates the actions of
      thrombin and accelerates activated protein C formation. TM is ubiquitous
      throughout the systemic microcirculation but is reduced in brain regions
      predisposed to lacunar infarction. We investigated whether TM is present within
      human nerve and differentially expressed according to vessel caliber and
      proximity to the blood-nerve barrier. Vascular endothelial TM was detected on
      sural nerve biopsies with immunohistochemistry. The proportion of TM-positive
      microvessels was expressed relative to total von Willebrand factor (vWF)-positive
      vessels. Although vWF was detectable in all microvessels, TM expression was
      absent from the perineurial vessels. TM was detected in 47% (15-80%, 95%
      confidence level) of larger epineurial arterioles, in 43% (30-61%) of smaller
      epineurial vessels, and in 30% (19-47%) of endoneurial vessels. These findings
      demonstrate that TM is present in human nerve microvasculature but is regionally
      deficient in proximity to the blood-nerve barrier, which may predispose nerve to
      microvascular ischemia in inflammatory/prothrombotic conditions.

PMID- 12210389
TI  - Influences of electromechanical events in defining skeletal muscle properties.
AB  - Inactivity of the cat soleus muscle was induced via spinal cord isolation (SI),
      and the cats were maintained for 4 months. The soleus was electrically stimulated
      while lengthening (SI-L) or shortening (SI-S) during a simulated step cycle or
      during isometric (SI-I) contractions. For the SI, SI-S, SI-L, and SI-I groups,
      the soleus weights were 33, 55, 55, and 64% of the control, respectively, and the
      maximum tetanic tensions were 15, 30, 36, and 44% of the control, respectively.
      The specific tension was lower in all SI groups than in the control. Absolute
      forces at stimulation frequencies of 5-200 Hz were smaller in all SI groups than
      in the control. The SI-I group tended to have higher values for all force-related
      parameters than the other SI groups. Fatigue resistance was similar among all
      groups. The isometric twitch time-to-peak tension was shorter, and the frequency
      of the stimulation-tension response was shifted to the right in all SI groups
      with respect to the control. Maximum shortening velocities were 70, 59, and 73%
      faster for the SI, SI-S, and SI-L groups and similar to the control for the SI-I
      group. Inactivity resulted in an increased percentage of faster myosin heavy
      chains (MHCs) that was blunted in the SI-I and SI-L groups but not in the SI-S
      group. Pure type I MHC fibers atrophied by 80, 59, 58, and 47% in the SI, SI-S,
      SI-L, and SI-I groups. The data from the SI group quantify the contribution of
      activity-independent factors in maintaining the mechanical and phenotypic
      properties of the cat soleus. Relative to a fast-fatigable muscle, these results
      suggest that only 25% of the slowness (type I MHC) and none of the resistance to
      fatigue of the soleus muscle are dependent on activity-related factors. Short,
      daily bouts of electromechanical activation ameliorated several of these
      adaptations, with the isometric contractions being the most effective
      countermeasure. The clinical implications of these findings for rehabilitation
      strategies are discussed.

PMID- 12210390
TI  - Activity-independent neural influences on cat soleus motor unit phenotypes.
AB  - The physiological and phenotypic properties of motor units in the cat soleus
      muscle were studied after 4 months of inactivity induced by spinal cord isolation
      (SI). The soleus of some SI cats were stimulated for 30 min/day during an
      isometric (SI-I), shortening (SI-S), or lengthening (SI-L) phase of a simulated
      step cycle. Mean maximum tetanic tensions were approximately 15, 26, 32, and 51%
      of the control in the SI, SI-S, SI-L, and SI-I groups. Mean time-to-peak tension
      was approximately 50% shorter than the control in all SI groups. One motor unit
      was glycogen-depleted in each muscle via repetitive stimulation. Eighteen
      physiologically slow and 9 fast motor units from the spinal cord-isolated groups
      consisted of fibers that contained only slow myosin heavy chain (MHC) and
      sarco(endo)plasmic reticulum calcium-adenotriphosphatase (SERCA) isoforms. Two
      motor units (physiologically fast) consisted primarily of fibers that contained
      both fast and slow MHC and SERCA. These data reflect a dissociation between
      isometric speed-related properties and MHC and SERCA isoforms following
      inactivity. The predominance of fibers containing both fast and slow MHC and
      SERCA isoforms in 2 motor units demonstrates a strong motoneuronal influence on
      the muscle-fiber phenotype even when the motoneurons are silent.

PMID- 12210391
TI  - Lack of apoptosis in patients with progressive external ophthalmoplegia and
      mutated adenine nucleotide translocator-1 gene.
AB  - Adenine nucleotide translocator-1 (ANT-1), encoded by chromosome 4 (4q34-35
      locus), is a component of the mitochondrial permeability transition pores that
      are involved in apoptotic mechanisms. We studied muscle biopsies from seven
      individuals with autosomal dominant progressive external ophthalmoplegia caused
      by ANT-1 mutations. We found no instance of terminal deoxynucleotidyltransferase
      mediated dUTP nick end labeling (TUNEL) positivity nor significant expression of
      apoptosis-related proteins. Furthermore, there was no morphological evidence of
      apoptosis at the ultrastructural level. Thus, degeneration of muscle in this
      disorder is nonapoptotic.

PMID- 12210392
TI  - Comparison of MRI and electrophysiological studies for detecting brainstem
      lesions in traumatic brain injury.
AB  - The yield of magnetic resonance imaging (MRI) and electrophysiological studies in
      detecting brainstem lesions was assessed in 35 patients suffering from traumatic
      brain injury (Glasgow Coma Scale, 3-10). As an inclusion criterion, all patients
      had brainstem trauma as revealed by early MRI or electrophysiological studies. Of
      the 35 cases, 7 (20%) had brainstem lesions detected by MRI only, whereas in 10
      patients (29%), electrophysiological examination disclosed impairment of
      brainstem function with normal MRI. In 18 (51%) subjects, both diagnostic
      techniques revealed brainstem lesions. The midbrain was the most common location
      of lesions. Masseter reflex recording had the highest yield (93%) of abnormal
      findings. No mismatch with respect to site and side of abnormality occurred
      between MRI and electrophysiological studies. Outcome analysis indicated an
      unfavorable course for the vast majority (83%) of patients, regardless of the
      diagnostic means disclosing traumatic brainstem injury. Therefore, both
      techniques are effective in disclosing traumatic brainstem injury, with
      diagnostic overlap in about 50% of cases. In contrast to MRI,
      electrophysiological investigation is easily performed and repeated at low cost
      in the setting of an intensive care unit, where such patients are typically
      hospitalized after trauma. In addition to electrophysiological assessment of
      brainstem function, MRI is recommended in each case having normal
      electrophysiological findings when brainstem injury is suspected.

PMID- 12210393
TI  - Molecular analysis of the superoxide dismutase 1 gene in Spanish patients with
      sporadic or familial amyotrophic lateral sclerosis.
AB  - We performed a genetic analysis of the Cu/Zn superoxide dismutase gene (SOD1) in
      Spanish patients with sporadic or familial amyotrophic lateral sclerosis (ALS).
      We found mutations in 2 of 11 families (18%) with ALS. In addition, 1 of the 87
      sporadic ALS patients studied harbored a mutation in the same gene. We identified
      G37R in exon 2 of the SOD1 gene in 1 family. Another patient, with sporadic ALS,
      showed a novel N65S in exon 3. In addition, we found a novel I112M in exon 4 in
      another family. Our data highlight the genetic heterogeneity of patients with ALS
      harboring mutations in the SOD1 gene and confirm that families with autosomal
      dominant inheritance of the trait, regardless of their ethnic background, are
      more likely to carry mutations in such a gene.

PMID- 12210394
TI  - Repetitive nerve stimulation of the nasalis muscle: technique and normal values.
AB  - A technique of repetitive nerve stimulation of the facial nerve with recording
      from the nasalis and orbicularis oculi muscles was developed and tested in 15
      healthy subjects. Quality criteria were that the stimulus artifact should return
      to baseline before the onset of the compound muscle action potential (CMAP), and
      that the CMAP should begin with a negative phase, be biphasic in shape, and have
      an amplitude of over 1 mV. Repetitive nerve stimulation was only performed if all
      four criteria were met, which was the case in all 15 subjects for the nasalis
      muscle, but in only 5 subjects for the orbicularis oculi muscle. The largest
      observed decrement was 9% in area. Reptitive nerve stimulation of the nasalis
      muscle is thus feasible, but its diagnostic utility remains to be established in
      patients with disorders of neuromuscular transmission.

PMID- 12210395
TI  - Axonal hyperpolarization associated with acute hypokalemia: multiple excitability
      measurements as indicators of the membrane potential of human axons.
AB  - Multiple nerve excitability measurements have been proposed for clinical testing
      of nerve function, and an important determinant of excitability is membrane
      potential. We report a patient with acquired hypokalemic paralysis in whom
      multiple excitability indices (stimulus-response curve, strength-duration
      properties, threshold electrotonus, recovery cycle) were measured during and
      after an acute hypokalemic attack (serum K(+) level, 2.1 mEq/L and 4.5 mEq/L,
      respectively). During hypokalemia, there was a shift of the stimulus-response
      curve to the right, a decrease in strength-duration time constant, a "fanning
      out" of responses during threshold electrotonus, a reduction in relative
      refractory period, and an increase in superexcitability; all of these indicate
      axonal hyperpolarization, presumably due to the K(+) equilibrium potential being
      more negative. These indices returned to normal 20 h later, associated with
      normalization of the serum K(+) level. These results demonstrate that the changes
      associated with hypokalemic paralysis are not confined to muscle and that axons
      undergo hyperpolarization in vivo. Multiple excitability measurements can be used
      as a tool to identify changes in membrane potential of human axons.

PMID- 12210396
TI  - Evaluating patients with suspected peripheral neuropathy: do the right thing, not
      everything.

PMID- 12210397
TI  - Obturator neuropathy due to obturator hernia.

PMID- 12210400
TI  - Genotypic and phenotypic analysis of the env gene from South African HIV-1
      subtype B and C isolates.
AB  - The objective of the study was to assess the genotypic and phenotypic properties
      of 18 viral strains from human immunodeficiency virus-1 (HIV-1) positive patients
      and to identify subtype C isolates for vaccine design strategies. All the
      isolates were non-syncytium-inducing (NSI) in both the primary and MT-2 cell
      cultures. The amino acid charge of the V3 loop correlated with the NSI phenotype
      of the strains. The V3 competitive peptide enzyme immunoassay and DNA sequencing
      of the partial gp120 region gave concordant results on the 15 subtype C strains,
      whereas the three B genotypes gave a positive to B, a nonreactive to B, and a
      dual reaction to the B-D peptides, respectively. Sixteen of the isolates used
      only CCR5 as coreceptor whereas two isolates made use of additional coreceptors
      including CXCR4. In summary, all our subtype C isolates are NSI phenotypically
      and almost all of them use CCR5 exclusively as their coreceptor.

PMID- 12210401
TI  - Susceptibility of diverse primary HIV isolates with varying co-receptor
      specificity's to CXCR4 antagonistic compounds.
AB  - The chemokine receptors CCR5 and CXCR4 are an obvious target for HIV therapies.
      Two compounds, T-22 and AMD-3100, have been shown to inhibit infection of CXCR4
      using HIV-1 isolates. The specificity of T-22 and AMD-3100 was further confirmed
      by their ability to block entry of HIV-1 in GHOST-CXCR4 transfected cells with no
      effect on viral entry in the GHOST-CCR5 cells. The ability of T-22 to block
      replication of diverse HIV-1 isolates (group M, subtypes A, B, D, E, and F as
      well as group O) and HIV-2 primary isolates with varying coreceptor specificities
      ranging from exclusive CCR5 usage to multiple coreceptor usage was examined in
      detail. T-22 was found to be highly effective (>90%) at blocking infection of
      diverse HIV-1 (subtypes A-F, and group O) and HIV-2 isolates that use multiple
      coreceptors in human PBMCs homozygous for a 32-bp deletion in CCR5 (CCR5-/-), but
      less effective in CCR5 +/+ PBMCs. Additionally, sequential primary HIV-1 isolates
      obtained from a longitudinal cohort who had switched from single coreceptor usage
      to a broad range of multiple receptors could be blocked effectively by both T-22
      and AMD-3100 in CCR5-/- PBMCs. Our data suggest that CXCR4 antagonistic compounds
      are highly effective in blocking the entry of X4-tropic HIV-1, and that these
      compounds could be a useful additive to current anti-retroviral therapy for
      clinical management of HIV disease.

PMID- 12210402
TI  - Effects of gag mutations on human immunodeficiency virus type 1 particle
      assembly, processing, and cyclophilin A incorporation.
AB  - A series of human immunodeficiency virus (HIV) mutants was constructed either by
      deletion or by linker insertion at various regions in the gag coding sequences.
      The ability of each mutant to assemble virus particles and to process them
      proteolytically, as well as incorporate cyclophilin A, was analyzed by Western
      immunoblot. This investigation indicated that most of the gag mutants were
      assembled and released at a level comparable to that of wild-type virus. In an
      assay involving a single cycle of infection, mutants containing significant
      levels of cyclophilin A showed less in trans interference effects on wild-type
      infectivity than did cyclophilin A-deficient mutants. Mutations in the N-terminal
      two-thirds of capsid protein severely disrupted cyclophilin A incorporation, but
      they affected virus processing only slightly to moderately. Virions released from
      cyclosporine-treated cells were processed, as well as virions made by the mock
      treated cells. Also, protease inhibitor treatment had no detectable effect on the
      cyclophilin A incorporation. These results indicate that cyclophilin A
      incorporation is not required for virus particle processing and that virus
      processing does not affect cyclophilin A incorporation.

PMID- 12210403
TI  - Kaposi's sarcoma herpesvirus and HIV-1 seroprevalences in prostitutes in
      Djibouti.
AB  - Kaposi's sarcoma herpesvirus (KSHV) is linked causally to Kaposi's sarcoma.
      Epidemiological studies have shown that KSHV transmission can occur during sex
      among homosexual men, but heterosexual transmission seems to be very rare in KSHV
      low prevalence countries. A seroepidemiological study was conducted to determine
      whether KSHV is transmitted sexually between heterosexuals in an endemic country.
      Sera from 282 subjects of African origin living in Djibouti were tested for
      antibodies to KSHV and HIV-1. Among the 282 individuals, 43 were female
      prostitutes working in the streets (group 1), 123 were female prostitutes working
      in luxury bars (group 2), 41 were non-prostitute females (group 3), and 75 were
      non-prostitute males (group 4). KSHV seroprevalence was 26, 20, 17, and 36% in
      groups 1, 2, 3, and 4, respectively. The seroprevalence of KSHV is not different
      between street or bar prostitutes and non-prostitute females (OR = 1.67; P = 0.34
      and OR = 1.18; P = 0.73). These results suggest that in this endemic country
      commercial sex work does not seem to be a risk factor for KSHV infection and
      provides evidence against heterosexual transmission of KSHV in the female
      population studied.

PMID- 12210404
TI  - Genetic characterization of hepatitis A virus isolates from Buenos Aires,
      Argentina.
AB  - The Hepatitis A virus (HAV) has been classified in seven different genotypes,
      which include human (I, II, III, and VII) and simian (IV, V, and VI) groups. The
      sequence analysis of HAV strains contributes to the molecular epidemiology of the
      virus. Although the infection with HAV is endemic in Argentina and vaccination is
      being implemented in this country, using both IA and IB strains, there are very
      few data on the genotypes of the circulating viruses. On the basis of the
      sequences of 20 isolates collected in Buenos Aires during a 2-year period
      (extended to 3 years by two additional specimens), we observed the presence of a
      single sub-genotype, IA, but with a high genetic diversity. We analyzed the VP1
      2A junction and also the VP3-VP1 region. Most of the Argentine isolates grouped
      in at least two clusters. One of these was related to South American strains,
      thus suggesting a co-circulation of related isolates in neighbor countries. The
      other cluster was composed only of Argentine specimens. Other sequences were more
      scattered along the phylogenetic tree. However, we demonstrated that a consistent
      genetic relatedness of sequences could only be inferred on the basis of a more
      extensive sequencing of each isolate.

PMID- 12210405
TI  - HBV subtype as a marker of the clinical course of chronic HBV infection in
      Japanese patients.
AB  - Hepatitis B virus (HBV) genotype C is predominant in Japan. However, many HBV
      subtypes are involved in each genotype, and the clinical manifestations in the
      patients associated with each subtype remain unknown. Therefore, we investigated
      the relationship between HBV subtype and clinical aspects of chronic HBV
      infection. The subtype of 237 patients with chronic HBV infection, including 74
      asymptomatic carriers, was determined. The subtypes of 110 HBV carriers
      undergoing long-term follow-up management were determined twice to detect
      subtypic changes. The clinical features of the patients were also studied with
      regard to presence or absence of subtypic change. The subtypic distribution in
      the 237 HBV carriers was as follows: subtype adr, 161 (68%); subtype adw, 25
      (11%); subtype adwr, 12 (5%); subtype ar, 24 (10%); subtype adyr, 4 (2%); and
      unclassified, 8 (3%). The proportion of asymptomatic carriers in patients with
      subtype adw was significantly higher than those in patients with subtype adr (56%
      vs. 28%, P < 0.05). In addition, the proportion of HCC in patients with subtype
      adwr was significantly higher than those in patients with subtype adr (25% vs.
      6%, P < 0.05). The prevalence of subtype adr in 74 asymptomatic carriers tended
      to decrease with age (82% in carriers aged < or =35 years vs 43% in those aged >
      or =61 years, P < 0.05). The subtypic change and the course of chronic HBV
      infection had no significant correlation. These results suggest that HBV subtypes
      are associated with the clinical course of chronic HBV infection.

PMID- 12210406
TI  - Factors associated with viral breakthrough in lamivudine monoprophylaxis of
      hepatitis B virus recurrence after liver transplantation.
AB  - This study aimed to investigate the factors associated with viral breakthrough
      among liver transplant recipients who receive lamivudine monoprophylaxis.
      Consecutive patients receiving liver transplantation for HBV-related liver
      disease from June 1999 to October 2000 were studied. All patients received
      lamivudine 100 mg daily pre- and post-transplant. Serum samples were collected
      before lamivudine treatment, before liver transplantation, and then every 3-6
      months after liver transplantation. Lamivudine-resistant mutations at the YMDD
      motif of HBV P gene were detected by direct sequencing and HBV DNA was quantified
      by real-time polymerase chain reaction (PCR). Ten patients, 7 males and 3
      females, aged 50.5 +/- 7.9 years, were studied. Three patients had fulminant
      hepatitis and 7 patients had end-stage cirrhosis before liver transplantation.
      Lamivudine was started at 4.5 (range 0-40) weeks before liver transplantation.
      The median post-transplant follow-up was 16 (range 12-23) months. Four patients
      developed YMDD mutations 10.5 (0-16) months after transplantation with relapse of
      viraemia (median 1,294, range 51-3,135 MEq/ml). All patients who developed YMDD
      mutants had end-stage liver cirrhosis, and HBV DNA were detectable on the day of
      liver transplantation (median 0.62, range 0.086-1.63 MEq/ml). On the contrary,
      all 3 patients transplanted for fulminant hepatitis did not have YMDD mutation.
      Among the 3 end-stage cirrhotic patients who had negative HBV DNA before liver
      transplantation, none developed YMDD mutation. In conclusion, patients
      transplanted for fulminant hepatitis B and cirrhotic patients in whom HBV DNA
      could be rendered PCR negative before liver transplantation are unlikely to
      develop YMDD mutation on lamivudine monoprophylaxis.

PMID- 12210407
TI  - Variation of hepatitis C virus load, hypervariable region 1 quasispecies and CD81
      hepatocyte expression in hepatocellular carcinoma and adjacent non-cancerous
      liver.
AB  - Hepatitis C virus (HCV) infection is etiologically associated with the
      development of hepatocellular carcinoma (HCC) worldwide. HCV has been reported to
      exist and replicate in both HCC and adjacent non-cancerous liver tissue, but
      limited information was available on HCV viral load and quasispecies composition
      in HCC relative to adjacent non-cancerous hepatocytes. Previous study has also
      suggested CD81, a surface hepatocyte protein, as a receptor for HCV. To clarify
      the above, HCV-RNA and CD81-RNA titers in 20 paired hepatectomized liver and
      serum were quantitatively measured by chemiluminescent RT-cPCR. Hypervariable
      region 1 (HVR-1) variations of parallel specimens were analyzed after subcloning
      in 6 patients. HCV-RNA levels in serum and non-cancerous liver were markedly
      higher for HCV genotype 1 than genotype non-1. HCV levels were markedly higher in
      non-cancerous liver than in HCC (P = 0.001) in a genotype-independent manner,
      with a mean ratio of 56:1 for non-cancerous tissue to HCC. Both non-cancerous and
      HCC tissues had the same level of CD81-RNA expression, which was not linked to
      HCV load. HCV-RNA quantity in both HCC and non-cancerous liver correlated with
      the number of HVR-1 quasispecies in the tissue, and distinct HVR-1 subclones
      existed.

PMID- 12210408
TI  - Intrahepatic MxA and PKR protein expression in chronic hepatitis C virus
      infection.
AB  - The therapeutic effect of interferon-alpha and ribavirin in the treatment of
      chronic hepatitis C viral infection is limited. To identify patient
      characteristics that may predict responsiveness to treatment, the intrahepatic
      protein expression of two directly induced IFN-alpha effector proteins, MxA and
      PKR, were studied. Forty liver biopsy samples from patients with a variety of
      chronic liver diseases were stained for MxA and PKR protein using
      immunohistochemical techniques. In a HCV patient cohort, 30 liver biopsies were
      stained for MxA and PKR protein prior to treatment with IFN-alpha and ribavirin.
      PKR protein expression was not upregulated in viral liver disease. In contrast,
      MxA protein expression was significantly upregulated in viral liver disease (P =
      0.005). In chronic HCV liver disease, moderate to strong cytoplasmic expression
      of MxA protein was observed in hepatocytes and monocytes, indicating endogenous
      hepatocellular IFN-alpha pathway activation. In the HCV patient cohort treated
      with combination therapy, strong pre-treatment MxA hepatocyte expression was
      predictive of a non-response to treatment (odds ratio 9.33; P = 0.01; 95%
      confidence interval 1.63-53.2). This effect was independent of HCV genotype and
      viral load. It is concluded that pretreatment hepatocellular MxA expression may
      become a useful predictor of response to combination treatment with IFN-alpha and
      ribavirin.

PMID- 12210409
TI  - Cellular glycosaminoglycans and low density lipoprotein receptor are involved in
      hepatitis C virus adsorption.
AB  - The initial binding of Hepatitis C virus (HCV) to the cell membrane is a critical
      determinant of pathogenesis. Two putative HCV receptors have been identified,
      CD81 and low-density lipoprotein receptor (LDLr). CD81 interacts in vitro with
      the HCV E2 envelope glycoprotein, and LDLr interacts with HCV present in human
      plasma. In order to characterize these potential receptors for HCV, virus from
      plasma, able to replicate in cell culture, was inoculated on Vero cells or human
      hepatocarcinoma cells. HCV adsorption was assessed by quantitating cell
      associated viral RNA by a real-time RT-PCR method. Anti-LDLr antibody, low and
      very low density lipoproteins inhibited significantly HCV adsorption, confirming
      the role of LDLr as HCV receptor. Only one out of the two anti-CD81 antibodies
      used in this study led to a partial inhibition of HCV binding. This study also
      highlights a role for glycosaminoglycans (GAGs) in HCV adsorption: treatment of
      virus with heparin led to 70% inhibition of attachment, as did desulfation of
      cellular GAGs. Treatment of Vero cells with heparin-lyase significantly inhibited
      virus attachment but by only 30%. These results demonstrate the complexity of the
      HCV binding step in which LDLr interacts strongly with HCV, whereas the
      interaction of HCV with GAGs and particularly with CD81 seem to be more moderate.

PMID- 12210410
TI  - Sequence analysis of pre-S/surface and pre-core/core promoter genes of hepatitis
      B virus in chronic hepatitis C patients with occult HBV infection.
AB  - Although occult hepatitis B virus (HBV) infection in individuals without
      detectable hepatitis B surface antigen (HBsAg) may occur and has been reported to
      be common in patients with chronic hepatitis C, the related molecular mechanisms
      remain unknown. With the polymerase chain reaction, serum HBV DNA was sought in
      100 HBsAg-negative patients with chronic hepatitis C virus (HCV)-infection. In
      those with occult HBV infection, possible genomic variability of HBV was
      evaluated by amplification and direct sequencing of pre-S, surface, and pre
      core/core promoter genes. In total, 10 of the 100 patients (10%) had detectable
      serum HBV DNA, documenting an occult HBV infection. A deletion mutant in the pre
      S gene was found in one patient and mutations of the a determinant of HBsAg were
      observed in 2. In addition, a novel core promoter mutant (a dinucleotide
      substitution: T-to-C at nucleotide 1,802 and T-to-G at nucleotide 1,803,
      T1802C/T1803G) was found frequently in patients with occult HBV infection as
      compared to sex- and age-matched HBsAg-positive patients (80 vs. 10%, P < 0.001).
      In conclusion, the data suggest occult HBV infection is not uncommon in chronic
      hepatitis C patients in Taiwan, and a novel core promoter mutant may be
      associated with the absence of circulating HBsAg in these patients.

PMID- 12210412
TI  - Immunoglobulin G antibody avidity assay for serodiagnosis of hepatitis C virus
      infection.
AB  - It has been reported that the avidity of specific IgG antibody is lower in
      primary viral infection than in chronic viral infection. However, few studies
      have been reported on the IgG avidity in hepatitis C virus (HCV) infection. In
      the present study, 36 patients with antibody to HCV (anti-HCV) were examined for
      IgG avidity by an enzyme immunoassay with or without urea elution. The avidity
      index was significantly low in patients with primary HCV infection (7.7 +/- 6.8%,
      mean +/- SD), compared with patients with chronic HCV infection (77.0 +/- 21.8%)
      and individuals with past HCV infection (44.5 +/- 12.6%). Temporal changes of IgG
      avidity were examined in six patients with primary HCV infection. The avidity
      index was low in the acute phase of the infection and then increased with time.
      These results suggest that the avidity assay for IgG anti-HCV is a useful method
      for distinguishing primary HCV infection from chronic or past HCV infection.

PMID- 12210413
TI  - Inhibition of clinical isolates of human cytomegalovirus and varicella zoster
      virus by PNU-183792, a 4-oxo-dihydroquinoline.
AB  - The susceptibility of human cytomegalovirus (CMV) and varicella zoster virus
      (VZV) clinical isolates to PNU-183792, a 4-oxo-dihydroquinoline, was examined.
      The antiviral potency of PNU-183792, a non-nucleoside inhibitor, was compared to
      the licensed nucleoside inhibitors ganciclovir and acyclovir using plaque
      reduction and virus yield reduction assays. PNU-183792 was as potent against CMV
      as ganciclovir and was superior in potency to acyclovir against VZV. PNU-183792
      represents a new class of non-nucleoside inhibitors of human herpesviruses.

PMID- 12210414
TI  - Unusual manifestations of primary cytomegalovirus infection in patients without
      HIV infection and without organ transplants.
AB  - Primary cytomegalovirus (CMV) infection with marked constitutional symptoms is
      rare in immunocompetent individuals and in those with iatrogenic
      immunosuppression, except transplant recipients. Four patients admitted to
      hospital with clinical illnesses associated with primary CMV infection were
      identified over a 12-month period. Their medical records were reviewed with
      regard to clinical and laboratory data, and outcome. Primary CMV infection was
      defined by the concomitant presence of CMV IgM and low avidity CMV IgG antibody.
      Of two patients with no known underlying illness, one presented with
      thrombocytopenic purpura and the other with vasculitis. Two patients receiving
      immunosuppressants for underlying ulcerative colitis presented with CMV-induced
      pancytopenia and CMV colitis. Atypical lymphocytosis was a feature on blood film
      examination in three of the four cases. One patient with disseminated CMV
      infection died of progressive multiorgan failure despite antiviral treatment. CMV
      disease following primary CMV infection should be considered in otherwise
      immunocompetent individuals with atypical lymphocytosis on blood film analysis,
      and particularly in patients on immunosuppressants such as those with ulcerative
      colitis, since early diagnosis and treatment with antiviral drugs may improve
      outcome.

PMID- 12210411
TI  - Genetic heterogeneity of the envelope 2 gene and eradication of hepatitis C virus
      after a second course of interferon-alpha.
AB  - The heterogeneity of the envelope 2 (E2) gene of the hepatitis C virus (HCV) was
      involved in the sensitivity of HCV to interferon-alpha (IFN-alpha). To assess the
      factors leading to virus eradication by IFN-alpha, patients whose first treatment
      by IFN-alpha failed and who had virus eradication after a second treatment were
      studied. These patients were paired with subjects in whom both treatments failed.
      The phosphorylation homology domain of the E2 gene (E2-PHD) had no sequence
      variation between the two stages in both groups of patients. Therefore, this
      region has no clinical predictive value within a specific genotype. The
      hypervariable region 1 (HVR1) was analyzed by cloning and sequencing 20 clones
      per sample. Comparison of samples showed that the change in quasispecies induced
      by the first IFN-alpha therapy could be associated with virus elimination
      obtained after a second treatment. The greater proportion of nonsynonymous
      mutations that was noted before the second treatment in responders suggest that
      pretherapeutic immune response is a major factor determining virus elimination
      and that the immune status of these patients changed between the first and the
      second treatment.

PMID- 12210415
TI  - Transient CD4/CD8 ratio inversion and aberrant immune activation during dengue
      virus infection.
AB  - The immune status after dengue virus infection was studied in dengue patients
      from an outbreak of serotype 3 dengue virus infection in the southern part of
      Taiwan during November and December 1998. Consecutive blood samples from 29
      dengue patients, of whom 21 had dengue fever and 8 had dengue hemorrhagic
      fever/dengue shock syndrome, were collected, and the immunophenotypes of the
      peripheral blood mononuclear cells were determined by flow cytometry. The early
      activation marker CD69 appeared on lymphocytes and monocytes at day 4 after the
      onset of fever, and declined afterward. However, a transient reverse in the
      CD4/CD8 ratio occurred at days 6-10 after the onset of fever. The CD4/CD8 ratio
      inversion was manifested in 10 of 29 dengue patients and was encountered more
      frequently in dengue hemorrhagic fever/dengue shock syndrome than in dengue fever
      patients. Analysis of the clinical blood cell count of these 10 cases showed that
      increase of immature neutrophils developed at fever days 5-6, CD4(dim) or
      CD8(dim) monocytosis at days 6-7, and atypical lymphocytosis at days 8-10 after
      the onset of fever. Serum IL-6 was found at either day 7 or day 9-11. The PHA
      stimulated T-cell response was depressed as well. These changes in immune
      parameters indicate aberrant immune activation during dengue virus infection and
      might be involved in the pathogenesis of dengue virus infection.

PMID- 12210416
TI  - Neurological complications of acute and persistent Epstein-Barr virus infection
      in paediatric patients.
AB  - Neurological complications of Epstein-Barr virus (EBV) have been reported almost
      exclusively in the course of acute primary infections. The role of EBV in
      paediatric neurological disease was investigated prospectively over a 2-year
      period, searching for acute primary, chronic, and reactivated EBV infections.
      Active EBV infections were diagnosed in 10/48 patients, including two with acute
      primary EBV infections (cranial neuritis and cerebellitis), one with chronic
      active infection (T/NK cell lymphoma with cranial neuritis), and seven with
      reactivated infections. Among these seven patients, three showed "Alice in
      Wonderland" syndrome, one facial nerve palsy, one progressive macrocephaly, and
      two prolonged encephalitic illness. The prognosis was good except for the patient
      with lethal T/NK cell lymphoma and the two girls with encephalitic illness.
      Despite steroid treatment, these girls suffered prolonged cognitive impairment
      and epileptic seizures. Both developed left-sided hippocampal atrophy, and one of
      them hippocampal sclerosis. Like primary infections, reactivated EBV infections
      cause neurological complications in a considerable number of paediatric patients,
      lead to serious long-term complications, and may contribute to the pathogenesis
      of hippocampal lesions.

PMID- 12210417
TI  - Detection of human herpesvirus 8 DNA in serum from blood donors with HHV-8
      antibodies indicates possible bloodborne virus transmission.
AB  - Human herpesvirus 8 (HHV-8) is associated with Kaposi's sarcoma. There is a high
      seroprevalence of HHV-8 in several African countries, but the transmission route
      is not known definitively. In this study 174 serum samples from blood donors in
      Tanzania were examined by immunofluorescence assays detecting antibodies to
      latent and lytic HHV-8 antigens. Real-time polymerase chain reaction was used for
      detection and quantification of HHV-8 DNA in serum. In all, 83/174 (48%) of the
      subjects had antibodies to latent or lytic antigens. Forty (23%) had antibodies
      to both antigens and of those eight (20%) had detectable HHV-8 DNA in serum. HHV
      8 DNA load correlated with antibody titres to lytic, but not latent, HHV-8
      antigens. This supports the usefulness of anti-lytic antibodies in HHV-8 serology
      and suggests that transmission of HHV-8 by blood contact could be of importance
      in this region.

PMID- 12210418
TI  - Human herpesvirus 6 and multiple sclerosis: a study of T cell cross-reactivity to
      viral and myelin basic protein antigens.
AB  - Several reports have suggested an association of human herpesvirus 6 (HHV-6) with
      multiple sclerosis. Autoreactive T lymphocytes directed against myelin components
      seem to contribute to the pathogenesis of the disease. It has been suggested that
      molecular mimicry between viral and self-antigens might be one of the mechanisms
      that determine the onset of several autoimmune diseases. Following this
      hypothesis, the purpose of the present study was to evaluate if HHV-6 could play
      a role in activating T cells capable of cross-reaction with an important myelin
      component, the myelin basic protein. T cell lines were established from 22
      multiple sclerosis patients and from 16 healthy controls, and their capability to
      react to both virus and myelin basic protein antigens was compared. The analysis
      of T cell cross-reactivity in patients and controls did not show significant
      differences in the HHV-6 ability to activate myelin basic protein-reactive T
      cells. Similarly, the evaluation of the humoral immune response to HHV-6 in
      patients and controls did not mirror any abnormality in the HHV-6 status in
      multiple sclerosis patients. Therefore, although the findings of activity in
      vitro of T cell lines with dual specificity are consistent with the hypothesis of
      molecular mimicry, the lack of differences in cross-reactivity between patients
      and controls do not support molecular mimicry as an important mechanism in the
      physiopathology of this disease.

PMID- 12210419
TI  - Genotype spectrum of cervical human papillomavirus infection among sexually
      transmitted disease clinic patients in Hong Kong.
AB  - Previous studies have suggested that a few uncommon human papillomavirus (HPV)
      genotypes are prevalent in Chinese cervical cancer patients. To elucidate the
      genotype spectrum of HPVs circulating among Hong Kong Chinese, a cross-sectional
      study was conducted on 553 women who attended a public sexually transmitted
      disease clinic. HPV DNA was detected from cervical samples using the polymerase
      chain reaction, followed by genotype identification based on restriction fragment
      length polymorphism and direct sequencing. The prevalence of HPV was 30.6% for
      all types combined, 14.8% for high-risk types, 10.8% for low-risk types, and 7.1%
      for unknown-risk types. Among the HPV-positive women, 89.9% had single type
      infections; whereas the other 10.1% harboured more than one HPV type. HPV11 was
      the most prevalent genotype, detected in 5.1% of subjects; followed by HPV16
      (4.9%), HPV58 (4.3%), HPV6 (3.3%), and HPV53 and CP8304 (2.2% each). Other less
      common genotypes found were HPV18, 33, 39, 61, LVX160, MM4, MM7 (range: 0.7
      1.6%); HPV26, 45, 54, 56, 59, and LVX100 (range: 0.4-0.5%); HPV35, 40, 52, 55,
      68, MM8, and MM9 (0.2% each). This study shows that HPV58 is the second most
      common high-risk HPV genotype circulating among Chinese female sexually
      transmitted disease clinic patients in Hong Kong. This together with previous
      reports of the high prevalence of HPV58 among Chinese cervical cancer patients
      accentuate the importance of developing vaccines targeting at this otherwise
      uncommon genotype.

PMID- 12210420
TI  - Replication of enhancer-deficient amphotropic murine leukemia virus in human
      fibrosarcoma but not in primary human fibroblasts.
AB  - Amphotropic murine leukemia virus (MLV) replicates in cells from various
      mammalian species including humans and is a potential contaminant in MLV vector
      preparations for human gene transfer studies. In general, MLV replication depends
      on the expression of viral genes under the control of 75 bp enhancer elements in
      the long terminal repeat. However, in specific human fibrosarcoma and lymphoma
      lines replication of amphotropic MLV is possible without these enhancers.
      Fibrosarcomas are malignant tumors of fibroblast origin. To test the replication
      potential of intact and enhancerless amphotropic MLV in untransformed cells,
      infection studies with these viruses were carried out in three types of primary
      human fibroblasts. Replication of amphotropic MLV is observed in two of three
      tested fibroblast strains. None of these primary human fibroblasts is permissive
      for enhancer-deficient MLV, suggesting that replication of this virus may be
      limited to transformed cells.

PMID- 12210421
TI  - Detection and differentiation of Norwalk virus by reverse transcription
      polymerase chain reaction and enzyme-linked immunosorbent assay.
AB  - We have developed a reverse transcription-polymerase chain reaction and enzyme
      linked immunosorbent assay (RT-PCR-ELISA), using genetic cluster-specific probes
      in a microtiter plate format, for the detection and differentiation of Norwalk
      virus (NV) in stool samples. The specificity of the RT-PCR-ELISA was confirmed by
      testing 76 stool specimens and 15 tissue culture fluids derived from growths of
      unrelated viruses. The sensitivity of the RT-PCR-ELISA was compared with
      conventional PCR and Southern hybridization by testing the four cDNA clones
      derived from the RNA-dependent RNA polymerase region of the NV68 (NV/GI) virus
      and viruses in the NV/GII/P1B, the NV/GII/P2A, and the NV/GII/P2B cluster. This
      assay was as sensitive as the conventional RT-PCR with Southern hybridization
      regardless of primer pairs and probes used in the experiments. However, the
      actual sensitivity of this method was higher when clinical stool samples were
      examined because this assay examines all the samples irrespective of the RT-PCR
      results. The RT-PCR-ELISA format is simple, time saving, and suitable for testing
      many samples. It should be reliable for large-scale epidemiological studies of
      NV.

PMID- 12210422
TI  - Mixed infections of adults and children with multiple TTV-like mini virus
      isolates.
AB  - Testing of the DNA of TTV-like mini virus (TLMV) was done with serum samples
      obtained from 184 patients (children and adults) who visited different outpatient
      clinics at a university hospital in Florianopolis, south of Brazil. TLMV DNA was
      detected by PCR primers from the non-coding region of the genome. A global TLMV
      prevalence of 78% was found (94% among children below 11 years). PCR products
      from three serum samples (patients A-C) were cloned, and the sequences with a
      length of 201-227 nucleotides were determined for 16-19 clones derived from each
      of the sera. Among the 16 clones derived from patient C, 15 were identical, and
      the remaining one had a sequence homology of 99%. In contrast, eight different
      sequences were obtained among the 19 clones derived from patient A, and 10
      distinct sequences were depicted among the 17 clones derived from the serum of
      patient B. Additionally, 13 clones derived from a saliva sample of patient B were
      sequenced, and seven different nucleotide sequences obtained. One particular
      sequence was predominant in both serum (8/17 clones) and saliva (7/13 clones) of
      patient B. On a phylogenetic tree, sequences derived from patient A (a 6-year-old
      boy), as well as those derived from patient B (a 24-year-old man), were located
      in five distinct evolutionary branches, taking a minimum divergence of 5% between
      branches. This suggested that adults and children are coinfected frequently with
      several TLMV isolates of different origins.

PMID- 12210423
TI  - Sustained high proportion of zidovudine-resistant HIV variants despite prolonged
      substitution of zidovudine by other nucleoside reverse transcriptase inhibitors.
AB  - The consequences of zidovudine (ZDV) replacement by other nucleoside reverse
      transcriptase inhibitors on the expression of resistance mutations at codons 215
      and 41 of the reverse transcriptase (RT) gene was investigated prospectively in
      66 patients harboring mutant genotypes who were changed to an effective two- or
      three-drug combination antiretroviral regimen. Quantitation of mutant (MUT) viral
      populations at codon 215 by means of RT-PCR with differential hybridization of
      amplicons specific for MUT and wild (WT) variants revealed no difference in the
      proportion of 215 MUT variants prior to (93.5 +/- 2.4%) and 12 to 20 months after
      (96.9 +/- 1.9%) ZDV replacement, independently of a therapeutic change for
      stavudine. The fitness of the variants harboring the ZDV-resistant MUT 215
      genotype following drug withdrawal was calculated to be 96 to 99% of that of the
      variants harboring the WT 215 genotype. The apparent stability of ZDV-resistant
      variants in the study population may have two main complementary explanations:
      persistent selective pressure secondary to partial cross-resistance due to the
      new regimens given after the therapeutic alteration and suppression of viral
      replication after the therapeutic alteration that could have hampered the
      replacement of less fit variants by fitter variants. These findings indicate
      that, at least within 15 months following discontinuation of ZDV, an effective
      antiretroviral therapy is insufficient to allow for ZDV-resistant strains to
      disappear, and thus to allow for the safe re-introduction of the drug.

PMID- 12210424
TI  - Prolonged hepatitis A infection in an HIV-1 seropositive patient.
AB  - Hepatitis A virus (HAV) is a worldwide disease; in most cases, it causes an acute
      self-limited illness that does not lead to a chronic state. The course of HAV
      viremia in a homosexual male with human immunodeficiency virus type 1 (HIV-1) and
      the correlation between HIV and HAV viral load, alanine aminotranferase (ALT)
      level, and CD4(+) lymphocyte count were investigated during the course of the
      infection. HAV RNA was detected quantitatively up to 256 days after clinical
      onset. To our knowledge, this specific case is the first report of a prolonged
      infection with hepatitis A in a male with HIV-1. The ALT levels decreased
      gradually; however, 286 days after clinical onset of hepatitis, ALT levels were
      three times higher than normal values. HIV viral load was not affected by the
      infection with HAV and CD4(+) cell count was stable during the course of the co
      infection. The duration and the high-titer viremia of hepatitis A virus in an
      immunodeficient patient constitute a serious risk of the spread of hepatitis A
      within this population. As inactivated HAV vaccine is safe in HIV-positive
      subjects, it would be wise to establish a strategy of preventive vaccination in
      this high-risk group.

PMID- 12210425
TI  - Higher prevalence of anti-HCV antibodies among HIV-positive compared to HIV
      negative inhabitants of Addis Ababa, Ethiopia.
AB  - Serum samples (n = 4,593) collected in 1994 as part of a representative household
      community survey of the population of Addis Ababa who were 0-49 years old were
      tested for hepatitis C (HCV) antibodies. A third generation ELISA was used for
      primary screening and a line immunoblot assay for confirmation. HCV antibody
      prevalence was 0.9% (95% CI, 0.6-1.2%) and higher among HIV-positive compared to
      HIV-negative individuals (4.5% vs. 0.8%, respectively, P < 0.001). Similar higher
      prevalence of HCV antibodies was seen among HIV-positive compared to HIV-negative
      antenatal care attenders (2.9% vs. 0.8%, respectively, P = 0.003, n = 1,725), and
      sex workers (5.3% vs. 1.3%, respectively, P = 0.02, n = 383). Such association
      between HCV and HIV infection has not been described previously in Africa. After
      stratification by HIV status, HCV prevalence among women of the general
      population was identical to that of sex workers, suggesting that HCV sexual
      transmission is not common in this population and that HIV infection does not
      enhance susceptibility to HCV sexual transmission.

PMID- 12210426
TI  - High prevalence of a variant of SENV in intravenous drug user HIV-infected
      patients.
AB  - The prevalence, route of transmission, and clinical significance of SEN virus
      (SENV) infection was evaluated in 715 samples obtained from 150 blood donors, 165
      patients infected by HIV, 150 with HCV/HBV infection, 80 with autoimmune
      diseases, 40 with Primary Immunodeficiency, 40 with sexually transmitted
      diseases, 40 polytransfused, and from 50 unselected patients. The identification
      of SENV-DNA was performed by polymerase chain reaction and hybridization,
      followed by an immunoenzymatic method that identify different SENV strains. SENV
      A variant is largely represented among HIV-infected patients, being found in 71%
      of HIV(+) intravenous drug users and in 26% of individuals that had acquired HIV
      through sex. A high prevalence of SENV-A was observed also in HIV- polytransfused
      (27%) or in patients with sexually transmitted diseases (30%). These percentages
      are significantly higher than those observed in an unselected population and in
      blood donors. Prevalence of SENV-A is, therefore, high among HIV(+) patients with
      parental risk of exposure, but this infection does not appear to influence the
      clinical or immune status of HIV(+) patients.

PMID- 12210427
TI  - Genotypes and S-gene variability of Mexican hepatitis B virus strains.
AB  - The genotypes and subtypes of 15 Mexican hepatitis B virus strains were
      determined by sequencing and phylogenetic analysis of the small S-gene. The most
      predominant strains were found to be divergent genotype/subtype F/adw4 strains
      (66.6%), followed by A/adw2 (20.0%), D/ayw3 (6.7%), and G/adw2 (6.7%). The S
      genes of the Mexican genotype F strains and two Nicaraguan strains described
      previously formed a subcluster with more than 4% divergence from the other
      strains within this genotype. The Mexican strains within genotypes A and D showed
      the highest homology with strains from Europe and the United States. Ten amino
      acid substitutions not described previously were found in the S-genes of strains
      from nine chronic carriers, whereas the S gene in strains from six acute
      hepatitis B patients were highly conserved as compared to their respective
      genotypes. One genotype F strain from an HBsAg positive chronic carrier had a T
      to A mutation at position 647, forming a translational stop at codon 216. Two
      genotype F strains from HBsAg negative chronic carriers had a Val180 instead of
      an Ala found in the other genotype F strains. This study shows that a divergent
      genotype F predominates in Mexican strains analyzed, which presented amino acid
      substitutions not reported previously outside the a determinant.

PMID- 12210428
TI  - Core promoter mutations (A(1762)T and G(1764)A) and viral genotype in chronic
      hepatitis B and hepatocellular carcinoma in Guangxi, China.
AB  - Hepatitis B viruses (HBV) with core promoter mutations (A(1762)T, G(1764)A) were
      found in a previous study to be highly prevalent in patients from Guangxi, China
      with hepatocellular carcinoma (HCC). The aim of this study was to determine
      whether the mutations are prevalent in areas of Guangxi with high and lower
      incidences of HCC and whether they are associated with other severe sequelae of
      chronic hepatitis B, including the development of cirrhosis. In addition, the
      genotypes of the various HBV sequences were determined. Core promoter mutations
      were significantly more common in HCC patients than asymptomatic carriers from
      both regions of Guangxi and also were common in patients with cirrhosis and
      chronic hepatitis. The data also support the hypothesis that genotype C HBV
      causes more severe liver disease than does genotype B.

PMID- 12210429
TI  - Hepatitis B virus transmission in Brazilian hemodialysis units: serological and
      molecular follow-up.
AB  - A serological and molecular study of hepatitis B virus (HBV) infection was
      carried out in dialysis units in Central Brazil. Between 1995 and 1999, serum
      samples from all HBsAg-positive hemodialysis patients (n = 43) were tested for
      HBeAg/anti-HBe and subtyping by monoclonal ELISA. HBV DNA was detected by PCR and
      positive samples were genotyped by restriction fragment polymorphism pattern
      (RFLP) methodology. TheHBsAg prevalence declined in this population during the
      survey period (12-5.8%). HBeAg and anti-HBe were detected in 23 (53.5%) and 18
      (41.9%) sera, respectively. Thirty-six samples could be HBsAg subtyped: 21 were
      subtype ayw(3), 14 belonged to adw(2) and one was identified as adw(4). HBV DNA
      was present in 30 serum samples. Of these, 20 (66.7%) were genotype D, 9 (30%)
      genotype A, and 1 (3.3%) genotype F. In addition, the RFLP pattern could be
      determined in samples from 18/20 genotype D patients: D3 (10 strains), D7 (7
      strains) and D4 (1 strain); from 8/9 genotype A patients: A1 (6 strains) and A3
      (2 strains); and from the patient infected with genotype F: F1. Patterns D3 and
      D7 were associated closely with HBV infection in the two largest hemodialysis
      units studied. These findings confirm the value of the RFLP method as an
      effective molecular epidemiological tool for elucidating HBV transmission in
      hemodialysis units.

PMID- 12210430
TI  - Naturally occurring hepatitis B surface gene variants in chronic hepatitis B
      virus infection: correlation with viral serotypes and clinical stages of liver
      disease.
AB  - Virus variants escaping from host immunity may be implicated in the pathogenesis
      of hepatitis B virus (HBV) infection. In this cross-sectional study, the
      association was evaluated of the frequency of amino acid variation within the
      immunogenic epitopes of surface gene with different disease stages of chronic HBV
      infection. The surface gene of HBV encompassing the a determinant (amino acids
      124-148) and the putative HLA class I restricted cytotoxic T lymphocyte (CTL)
      epitope (amino acids 28- 51) were amplified and directly sequenced in 33
      asymptomatic carriers (Group I), 31 patients with chronic hepatitis (Group II),
      22 with cirrhosis (Group III), and 36 with hepatocellular carcinoma (Group IV).
      The amino acid sequences were compared subsequently with the consensus sequences
      of HBV serotype adw or adr. The frequency of amino acid variation per site per
      sequence (FEQ) was analyzed by generalized estimating equation with Poisson model
      after stratification by clinical and virological features. The FEQ was 1.21%
      overall, and was highest in Group IV patients and in patients above 50 years of
      age. In contrast, nine Group IV patients aged below 50 years who were infected
      with serotype adw had an inversely higher FEQ than those above 50; the age effect
      among hepatocellular carcinoma patients was significantly different from that
      among non-cancerous patients (P = 0.04). Variation of amino acid clustered within
      a determinant and CTL epitope for serotype adw but was distributed at random for
      serotype adr. Mutation hotspots differed between serotypes adw and adr. The FEQ
      of HBV surface protein is correlated positively with advancing age and severity
      of liver disease, and certain variants may contribute to the persistence of HBV
      infection.

PMID- 12210431
TI  - Drift in the hypervariable region of the hepatitis C virus during 27 years in two
      patients.
AB  - Serial serum samples were obtained over a 27-year period from a hepatitis C virus
      (HCV)-infected patient and from a nurse who appeared to become infected by this
      patient. The hypervariable region 1 (HVR1) and 5'noncoding region (5'NCR) of the
      HCV genome were amplified from each serum sample by polymerase chain reaction
      (PCR) and cloned. In the first serum specimen from the patient and the first two
      serum specimens from the nurse, most of the 20 clones from each serum sample had
      one common sequence in the HVR1 gene. All later serum samples contained a
      heterogeneous mixture of HCV quasispecies. The uniformity of the HVR1 sequence in
      the early samples and the emergence of greater diversity in later serum samples
      is consistent with the apparent transmission of HCV between the patient and nurse
      and the eventual emergence of other quasispecies as the virus replicated in the
      new host. In addition, the immune globulin given to the nurse may have been
      responsible for some of the HCV quasispecies changes observed in her serum.

PMID- 12210432
TI  - Long-term patterns of hepatitis C virus RNA concentrations in a cohort of HIV
      seronegative men with bleeding disorders.
AB  - Little is known about the natural history of hepatitis C virus (HCV) RNA
      concentrations over the course of infection. The aim of this study was to
      describe the natural history of HCV RNA concentrations in 85 HIV negative men
      with bleeding disorders infected with HCV for up to 30 years. HCV RNA
      concentrations were measured in yearly serum samples using a branched DNA assay.
      HCV RNA concentrations increased over time in this cohort. Two years after
      exposure to HCV, 53% of patients had undetectable concentrations and no patients
      had levels >7 log(10)(genome Eq/ml); by 20 years, these proportions had changed
      to 23% and 32% respectively. The RNA concentration correlated strongly with
      alanine aminotransferase (ALT; correlations of 0.41-0.71 depending on stage of
      infection) and aspartate aminotransferase (AST; 0.20-0.51) levels. Patients with
      haemophilia A had significantly higher HCV concentrations than those with other
      disorders. An effect of HCV genotype on HCV RNA concentrations became
      nonsignificant after excluding patients who were persistently HCV PCR negative
      and who could not be genotyped. The correlation of HCV RNA concentrations with
      other markers of liver function, such as ALT, means that studies with clinical
      outcomes are required to assess whether HCV RNA concentrations provide additional
      prognostic information to that provided by these other markers.

PMID- 12210433
TI  - Direct evidence for GB virus C/hepatitis G virus (GBV-C/HGV) superinfection:
      elimination of resident viral strain by donor strain in a patient undergoing
      liver transplantation.
AB  - The viral genome of GB virus C/hepatitis G virus (GBV-C/HGV), a single-strand RNA
      virus, is subject to considerable variability and at least four genotypes have
      been suggested based on phylogenetic analysis. While co-infection of GBV-C/HGV
      with other infectious agents such as hepatitis C virus (HCV) has been frequently
      observed, there is no report whether or not co-infection and/or superinfection
      occurs among different GBV-C/HGV strains. By studying a GBV-C/HGV positive
      recipient/donor pair in the context of undergoing liver transplantation, we have
      sequenced multiple clones derived from serum samples serially collected over four
      years. Detailed phylogenetic analyses have been performed with these sequences.
      The donor was infected with GBV-C/HGV genotype 1 and this strain completely
      replaced recipient GBV-C/HGV strain (genotype 2) after liver transplantation. The
      recipient's original viral strain became undetectable during follow-up. Sequence
      analysis failed to identify genetic recombination between the two genotypes, at
      least in whole structural domain. This study, therefore, provides direct evidence
      for GBV-C/HGV superinfection of one strain by another with one of them
      predominating probably due to replication competition.

PMID- 12210434
TI  - Large-scale comparison of experimental adjuvants with herpes simplex virus
      vaccine reveals a correlation of protection with IgG2a and IgG2b responses.
AB  - The potential of a large number of commercial and experimental adjuvant
      preparations to enhance the immunogenicity of an HSV-1 glycoprotein subunit
      vaccine was investigated. Evaluation was based on toxicity, HSV-specific antibody
      production, and protection against lethal challenge. All adjuvants tested
      increased the titer of antigen specific Ig levels when compared to subunit
      vaccine alone. However, following challenge, a broad range of protective
      responses were noted. Statistically significant correlations were observed
      between IgG antibody levels post immunization and the observed protection and
      these were particularly associated with antibodies of the IgG2a and IgG2b
      subclasses. The results emphasize the requirement of adjuvants for vaccine
      formulation when using subunit preparations, and demonstrate that the magnitude
      and efficacy of the induced immune response varies greatly with the choice of
      adjuvant.

PMID- 12210435
TI  - Herpes simplex virus type 1 variants arising after selection with an antiviral
      carrageenan: lack of correlation between drug susceptibility and syn phenotype.
AB  - Natural carrageenans of diverse structural types isolated from the red seaweed
      Gigartina skottsbergii were recently identified as potent and selective
      inhibitors of herpes simplex virus types 1 and 2 (HSV-1 and -2). The mu/nu
      carrageenan 1C3 was tested in vitro for its ability to select resistant variants.
      After serial passages of HSV-1 strain F in Vero cells in the presence of
      increasing concentrations of 1C3, viruses emerged that were approximately 2- to
      10-fold more resistant to 1C3 inhibition than parental virus; these viruses
      formed large plaques with an altered syncytial phenotype (1C3-syn). Plaque
      purified syncytial variants isolated from passages 13 and 14 have shown variable
      levels of resistance to 1C3, as well as to the other antiviral carrageenans
      isolated from G. skottsbergii and to other sulfated polysaccharides with known
      antiviral activity, such as heparin and dextran sulfate 8000, but all the clones
      were susceptible to acyclovir. The syn phenotype was not related to
      polysaccharide resistance. All the 1C3-syn variants formed large syncytia in Vero
      and CV-1 cells but did not induce fusion in other cell types. The growth
      efficiency in Vero cells, as well as the virulence for mice by intracerebral or
      intraperitoneal inoculation of 1C3-syn variants, showed no significant
      alterations in comparison with the parental virus. The syncytial properties were
      not affected by cyclosporine or melittin, suggesting that an alteration on
      glycoprotein gB could be responsible for the syn phenotype induced by 1C3.

PMID- 12210436
TI  - Bone marrow transplantation in a child with Wiskott-Aldrich syndrome latently
      infected with acyclovir-resistant (ACV(r)) herpes simplex virus type 1: emergence
      of foscarnet-resistant virus originating from the ACV(r) virus.
AB  - A human leukocyte antigen (HLA)-matched unrelated bone marrow transplantation
      (BMT) was performed in a 13-year-old patient with the congenital immunodeficiency
      syndrome, Wiskott-Aldrich syndrome. The patient had a history of acyclovir (ACV)
      resistant (ACV(r)) herpes simplex virus type 1 (HSV-1) infections prior to BMT.
      After BMT, the skin lesions caused by HSV-1 relapsed on the face and genito-anal
      areas. Ganciclovir (GCV) therapy was initiated, but the mucocutaneous lesions
      worsened. An HSV-1 isolate recovered from the lesions during this episode was
      resistant to both ACV and GCV. The ACV(r) isolate was confirmed to have the same
      mutation in the viral thymidine kinase (TK) gene as that of the previously
      isolated ACV(r) isolates from the patient. After treatment switch to foscarnet
      (PFA), there was a satisfactory remission but not a complete recovery. Although
      the mucocutaneous lesions improved, a PFA-resistant (PFA(r)) HSV-1 was isolated 1
      month after the start of PFA therapy. The PFA(r) HSV-1 isolate coded for the same
      mutation in the viral TK gene as the ACV(r) HSV-1 isolates. Furthermore, the
      PFA(r) isolate also expressed a mutated viral DNA polymerase (DNA pol) with an
      amino acid (Gly) substitution for Val at position 715. This is the first report
      on the clinical course of a BMT-associated ACV(r) HSV-1 infection that
      subsequently developed resistance to foscarnet as well.

PMID- 12210437
TI  - Molecular analysis of measles virus genome derived from SSPE and acute measles
      patients in Papua, New Guinea.
AB  - A very high annual incidence of 56 per million population below the age of 20
      years for subacute sclerosing panencephalitis (SSPE) has been reported from Papua
      New Guinea (PNG). In a more recent study, we have confirmed this unusual high
      incidence for Eastern Highlands Province (EHP) of PNG. In the study, it was
      observed that the vaccination rate among SSPE patients registered at Goroka Base
      General Hospital (GBGH) in EHP was higher than that of other infants in the
      province in recent years. To identify the measles virus (MV) responsible for SSPE
      in EHP, sequence analysis of hypervariable region of the N gene was performed
      from 13 MV genomes: 2 amplified from clinical specimens of SSPE patients and 11
      from acute measles patients. In 2 cases among the 11 with acute measles,
      nucleotide sequence of the entire H gene derived from isolated viruses was
      determined. Both nucleotide sequence and phylogenetic tree analyses showed that
      the amplified MV cDNAs were closely related to one another and belonged to the D3
      genotype though they were different from any previously reported MV sequences. No
      genome sequences of vaccine strains were detected. These findings suggest that
      the MV strains prevailing in the highlands of PNG belong to genotype D3 of the MV
      and this wild-type MV rather than the vaccine strains was likely to be
      responsible for SSPE in these patients.

PMID- 12210438
TI  - Norwalk-like virus 95/96-US strain is a major cause of gastroenteritis outbreaks
      in Australia.
AB  - Norwalk-like viruses (NLVs) were detected using a nested reverse transcriptase
      polymerase chain reaction (RT-PCR) with primers directed to the RNA polymerase
      region. Samples were examined from 11 separate outbreaks of gastroenteritis and
      five sporadic cases of childhood gastroenteritis between 1997 and 2000.
      Phylogenetic analysis of the 298 bp sequences showed that all strains belong to
      NLV genogroup II and the majority of the sequenced isolates (30/36) were members
      of the 95/96-US subset of strains associated with outbreaks recorded worldwide
      between 1995 and 1996. This was confirmed by analysis of the full length capsid
      region of a representative Australian isolate. This study demonstrates the
      usefulness of targeting primers for NLVs to the predominant circulating
      genotype(s) and confirms the spread of this subtype globally, including the
      Southern Hemisphere.

PMID- 12210439
TI  - Systemic and intestinal antibody responses to NSP4 enterotoxin of Wa human
      rotavirus in a gnotobiotic pig model of human rotavirus disease.
AB  - Antibody responses to the Wa human rotavirus (HRV) nonstructural protein NSP4, a
      viral enterotoxin, were evaluated in neonatal gnotobiotic (Gn) pigs. Gn pigs were
      inoculated orally with one dose of 10(5) fluorescent focus units (FFU) of
      virulent Wa HRV (HRV-V), to mimic natural infection, or with three doses of 5 x
      10(7) FFU attenuated Wa HRV (HRV-A) at 10-day intervals, to mimic oral attenuated
      rotavirus vaccines, or they were mock inoculated (mock). Subsets of pigs were
      challenged with 10(6) FFU of virulent Wa HRV at post-inoculation day 28 (PID 28).
      Post-challenge, the HRV-V pigs were completely protected against diarrhea and
      virus shedding, whereas the HRV-A pigs had a 50% protection rate against diarrhea
      and a 67% protection rate against virus shedding. All mock-inoculated pigs shed
      virus and had diarrhea post-challenge. Isotype antibody titers to NSP4 were
      compared in serum and intestinal contents, at post-inoculation day (PID) 28 and
      at post-challenge day 7 (PCD 7/PID 35) by indirect ELISA, using purified
      recombinant NH2-6xHis-tagged NSP4 of virulent Wa HRV. Pre-challenge, both the HRV
      V and HRV-A-inoculated pigs had similar moderate titers of serum IgG antibodies
      to NSP4. However, only the HRV-V-inoculated pigs developed detectable serum and
      intestinal IgA antibody titers to NSP4 pre-challenge, compared with the HRV-A
      inoculated pigs. The mock-inoculated pigs had no IgM, IgA, or IgG antibodies to
      NSP4 pre-challenge. All Wa HRV-inoculated pigs developed low to moderate titers
      of serum IgM, IgG, and IgA antibodies to NSP4 post-challenge, but the mock
      inoculated pigs had only IgM antibodies post-challenge. Both Wa HRV-inoculated
      groups developed low titers of IgA antibody to NSP4 in the small intestinal
      contents post-challenge, but titers were 5.8-fold higher in the HRV-V pigs. Our
      results concur with findings that both rotavirus vaccinated and naturally
      infected children seroconvert with modest IgG antibodies to NSP4 [Johansen et al.
      (1999) J Med Virol 59:369-367]. These data suggest that Gn pigs could be a useful
      model to evaluate serum and intestinal IgA antibodies to NSP4 and their role in
      protection against HRV infection. Further experiments may clarify whether (1) the
      NSP4 antibodies detected pre-challenge in the HRV-V pigs contribute to the higher
      protection rates observed, or (2) the reduced or delayed NSP4 antibody responses
      of the HRV-A pigs are associated with the lower protection rates in these pigs.

PMID- 12210440
TI  - Infection of simian B lymphoblastoid cells with simian immunodeficiency virus is
      associated with upregulation of CD23 and CD40 cell surface markers.
AB  - Simian immunodeficiency virus (SIV) as well as human immunodeficiency virus (HIV)
      induce polyclonal B-cell activation and are associated with the appearance of
      lymphomas in their respective hosts in either the presence or the absence of
      other co-infecting viruses such as Epstein-Barr virus (EBV). However, the
      pathogenic role of these retroviruses in the development of lymphoproliferative
      disorders remains poorly understood. To explore the virus-B-cell interactions,
      two immortalized lymphoblastoid B-cell lines (SL-P1 and SL-691) were established
      from cynomolgus monkeys that were naturally co-infected with a simian type D
      retrovirus-2 (SRV-2) and with the herpes virus Macaca fascicularis (HVMF-1). We
      addressed their susceptibility to SIV infection and the phenotypic modifications
      associated with SIV infection. In response, both cell lines (1) were co-infected
      with HVMF-1 (latent infection) and with SRV-2 (productive infection), (2) had a
      transformed phenotype because they did not require exogenous growth factors, and
      (3) when injected into mice with severe combined immunodeficiency (SCID),
      generated serially transplantable tumors. The B-cell origin of SL cells was
      demonstrated by the presence of rearrangements of the IgH gene and by the
      expression of typical B-cell lineage markers, such as CD20. SL-P1 and SL-691
      could be discriminated on the basis of different expressions of CD23 and CD40 and
      of kappa- and lambda-chains. Most importantly, SL-691 cells, but not SL-P1 cells,
      were susceptible to chronic noncytolytic SIV infection. This infection occurred
      in a CD4/CCR5/CXCR4-independent manner and was associated with the upregulated
      expression of CD23 and CD40 cell surface markers. In addition, CD20 expression,
      which progressively disappeared in SL-691 noninfected cells, was maintained in
      the SIV-infected counterpart. These findings support the hypothesis that SIV
      induce phenotypic perturbations in B cells that might eventually contribute to
      the development of lymphoproliferative disease.

PMID- 12210442
TI  - Epidemiology of cancer in adolescents.
AB  - In western populations, the annual incidence rate of cancer among adolescents
      aged 15-19 years is around 150-200 per million, intermediate between the rates
      for older children and young adults. The most frequent diagnostic groups are
      acute leukemia, lymphomas, central nervous system tumors, bone and soft tissue
      sarcomas, germ cell tumors, thyroid carcinoma, and malignant melanoma. While the
      causes of most cancers in teenagers are still unknown, health education and
      promotion and public health programs offer some scope for prevention among people
      of this age group. Reduction in sun exposure should lead to a reduction in
      incidence of melanoma, and elimination of hepatitis B in regions where it is
      endemic should result in a decrease in hepatic carcinoma. Five-year survival of
      patients diagnosed around 1990 exceeded 70% in the USA and UK. Entry to clinical
      trials appears to be much less frequent for adolescents with cancer than for
      children. There is some evidence that higher survival is associated with entry to
      trials or centralized treatment for certain cancers in this age group.

PMID- 12210443
TI  - Long-term survival of children with neuroblastoma prior to the neuroblastoma
      screening project in Germany.
AB  - BACKGROUND: In the last decades, prognosis of children with neuroblastoma has
      improved only slightly. Traditional estimates of survival reflect the survival
      experience of children diagnosed many years ago, and may thus not capture more
      recent progress in prognosis. We applied a new method of survival analysis,
      denoted period analysis, to provide more up-to-date estimates of long-term
      prognosis. We selected the cases diagnosed before the German neuroblastoma
      screening project in 1995, allowing to assess the method by comparing the 1994
      projected survival estimates with the observations made today (2000). PROCEDURE:
      The data comes from the population based German Childhood Cancer Registry. We
      included all 1,353 children diagnosed with neuroblastoma below age 15 between
      1980 and 1994. We derived 5-, 10-, and 15-year survival estimates using
      traditional analysis or period analysis as needed. Where possible we compared the
      period analysis estimates with the later obtained actual estimates. We showed
      trends in survival for the sample as a whole and for prognostic subgroups.
      RESULTS: Survival probabilities increased over time especially in the subgroups
      with poor prognosis. Short-term survival probabilities improved more than long
      term survival probabilities. Evaluation of the period-analysis estimates showed
      them to provide accurate and timely projections of prognosis of newly diagnosed
      patients. CONCLUSIONS: The results suggest major improvements in prognosis of
      children with neuroblastoma, even prior to the start of the German neuroblastoma
      screening project, especially in advanced disease. This could have been disclosed
      with the application of the period analysis method in 1995 even then with
      considerable accuracy. We recommend a more widespread application of this method
      especially in population-based cancer registries.

PMID- 12210444
TI  - Prospective study of carboplatin-based chemotherapy for pediatric germ cell
      tumors.
AB  - BACKGROUND: Survival of pediatric patients with malignant germ cell tumors has
      improved dramatically with the use of cisplatin-based chemotherapy, though
      patients are at high risk of significant long-term complications. In a
      prospective study, carboplatin was substituted for cisplatin in an attempt to
      minimize nephro- and oto-toxicities, while achieving excellent disease-free
      survival. PROCEDURE: All consecutive patients with malignant germ cell tumors at
      The Children's Hospital of Philadelphia were treated between 1989 and 1998. After
      pathologic confirmation of disease and pretreatment evaluation of pulmonary,
      renal, and otologic function, patients received etoposide 150 mg/m(2) days 1, 2,
      3; carboplatin 600 mg/m(2) day 2; and bleomycin 10 mg/m(2) day 3 for at least
      four courses. RESULTS: Twenty-three patients were entered for study, and were
      available for evaluation. All patients achieved either a complete or partial
      remission following therapy with surgery and chemotherapy. With a median of 58
      months of follow-up, overall survival is 91% and event-free survival is 87%.
      Therapy was given as an outpatient, and well tolerated, with 20 admissions for
      fever and neutropenia. Ototoxicity and nephrotoxicity, when evaluated, have been
      extremely limited. Three patients, all with stage III disease, have relapsed; one
      of these remains alive and disease free. CONCLUSIONS: Carboplatin can
      successfully substitute for cisplatin during the treatment of pediatric germ cell
      tumors without sacrificing response or survival. Long-term effects, especially
      nephrotoxicity and ototoxicity, were rare or mild among the small number of
      patients evaluated. Carboplatin appears to be a safe and efficacious alternative
      in the treatment of germ cell tumors, and should be considered as primary therapy
      for pediatric patients.

PMID- 12210445
TI  - Activity of postoperative carboplatin, etoposide, and high-dose methotrexate in
      pediatric CNS embryonal tumors: results of a phase II study in newly diagnosed
      children.
AB  - BACKGROUND: Chemotherapy is used as an alternative to irradiation or to minimize
      the irradiation exposure among infants with medulloblastoma or other CNS
      embryonal tumors. Adjuvant chemotherapy is commonly used in older children with
      high-risk medulloblastoma to improve survival or to allow a reduction in the
      craniospinal irradiation dose in standard-risk patients. However, optimal
      multimodality therapy, including the precise role of chemotherapy, has not been
      defined for these groups of patients. The objective of the present study is to
      assess the efficacy and toxicity of four postoperative courses of carboplatin,
      etoposide, and high-dose methotrexate in newly diagnosed children with
      medulloblastoma or other CNS embryonal tumors. PROCEDURE: Twenty-eight children,
      aged from 0.3 to 15.9 years (median, 6.2 years) with post-operative measurable
      residual CNS embryonal tumors were enrolled, comprising medulloblastoma (n = 19),
      supratentorial PNET (n = 7), and pineoblastoma (n = 2). Post-operative
      chemotherapy comprised carboplatin 350 mg/m(2) and etoposide 100 mg/m(2) on Days
      1 & 2, and methotrexate 8 g/m(2) on Day 3, repeated at 21-28-day intervals for a
      total of four courses. Therapy following completion of the initial Phase II study
      was influenced by patient age and investigator preference. RESULTS: The combined
      complete response rate (CR, 7/19) and partial response rate (PR, 7/19) was 74% in
      patients with medulloblastoma, 89% for patients with PNET/pineoblastoma (CR, 2/9
      and PR, 6/9), and for all patients it was 79%. Patients aged < 3 years at
      diagnosis had a combined PR and CR rate of 71% compared to 81% in patients aged >
      3 years. Treatment was well tolerated although myelosuppression and
      thrombocytopenia were common. CONCLUSIONS: The combination of carboplatin,
      etoposide, and high-dose methotrexate is highly active in pediatric patients with
      CNS embryonal tumors.

PMID- 12210446
TI  - Clinical utility of bronchoalveolar lavage in pediatric cancer patients.
AB  - BACKGROUND: Pulmonary disease in the pediatric cancer patient continues to pose a
      difficult clinical dilemma. Bronchoalveolar lavage (BAL) is commonly utilized for
      the diagnosis of pulmonary complications in the immunocompromised child.
      PROCEDURE: We retrospectively reviewed 53 BAL procedures performed in pediatric
      cancer patients with pulmonary disease between 1988 and 1998 to determine the
      diagnostic and clinical utility of BAL. Patients who had undergone prior
      myeloablative therapy were excluded from analysis. RESULTS: The majority of
      patients (83%) had an underlying diagnosis of acute leukemia or lymphoma. BAL
      yielded a specific diagnosis in 16 patients (30%), including 15 infections and 1
      malignant infiltration. Medical management was altered in an additional 14
      patients (26%) as a consequence of a negative BAL result. Severe but transient
      complications associated with the BAL procedure occurred in four patients (8%).
      Minor complications following the BAL occurred in 21 patients (40%) and included
      transiently increased oxygen requirement and anesthesia-related gastrointestinal
      complaints. The mortality from lung disease in this patient population was 7.5%.
      CONCLUSIONS: Both positive and negative BAL results contribute to the management
      of pediatric cancer patients with pulmonary disease. The low incidence of
      significant complications associated with BAL and the high mortality rate in this
      patient population support the choice of BAL as an initial diagnostic test in
      pediatric cancer patients with pulmonary disease.

PMID- 12210447
TI  - Normal monocyte-derived dendritic cell function in patients with Langerhans-cell
      histiocytosis.
AB  - BACKGROUND: Langerhans cell histiocytosis (LCH) is a histiocytic disease,
      characterized by the lesional accumulation of dendritic Langerhans cells together
      with T cells and eosinophils. The cause of this disease is unknown. Langerhans
      cells are bone marrow-derived dendritic cells (DCs), which can develop from
      CD34(+) hematopoietic progenitor cells as well as from monocytes. PROCEDURE: To
      test whether LCH patients have a general functional defect present in cells of
      their DC lineage, we generated immature DCs by culturing monocytes from nine
      patients with single- or multisystem LCH with GM-CSF and IL-4, and analyzed their
      phenotype and function before and after an in vitro maturation stimulus. Immature
      DCs were analyzed for their phenotype and cytokine production, DCs matured in
      response to TNF-alpha plus PGE(2) were analyzed for their phenotype, their
      stimulatory capacity in MLR, cell aggregation, and activation-induced apoptosis.
      RESULTS: In summary, no difference was found between both immature as well as
      mature DCs generated from patients and controls regarding the expression of CD1a,
      CD80, CD86, MHC class I, and MCH class II antigens. Similarly, no difference was
      found regarding IL-10, -12, and TNF-alpha production, as well as regarding cell
      aggregation and apoptosis in response to external stimuli. CONCLUSIONS: The
      absence of gross functional abnormalities in DCs generated from monocytes from
      patients with LCH makes the existence of a severe functional defect affecting all
      cells of the DC lineage in these patients unlikely.

PMID- 12210448
TI  - No association between Langerhans cell histiocytosis and human herpes virus 8.

PMID- 12210449
TI  - Incidence and trends in pediatric malignancies medulloblastoma/primitive
      neuroectodermal tumor: a SEER update. Surveillance Epidemiology and End Results.
AB  - BACKGROUND: It has been suggested that cerebellar medulloblastoma (M) and
      primitive neuroectodermal tumors (PNET) arising elsewhere in the nervous system,
      represent a single entity (M/PNET), although this concept is controversial.
      Cancer registries permit population-based description of cases reported as
      medulloblastoma, those reported as PNET and description of the aggregate, M/PNET.
      PROCEDURE: We reviewed the 768 cases of M/PNET (633 diagnosed medulloblastoma and
      135 diagnosed PNET) among persons under 20 years of age in the National Cancer
      Institute's Surveillance Epidemiology and End Results (SEER) database. RESULTS:
      The incidence of M/PNET rose 23%, from 4 per 10(6) person-years in 1973-77 to 4.9
      per 10(6) person-years in 1993-98. Cases reported as PNET were more likely than
      those reported as medulloblastoma to be supratentorial (30.4% vs. 1.9%, P <
      0.001) and to be female (42.2% vs. 35.4%, P = 0.13). The difference in 5-year
      survival between the 600 children with infratentorial medulloblastoma vs. the 49
      children with infratentorial PNET was not statistically significant (55% vs.
      43%). Regardless of reporting diagnosis, survival was poorer among children age 0
      3 years and those with supratentorial tumors. Children diagnosed in the more
      recent period from 1985-1998 had a longer median survival than children diagnosed
      in 1973-84 (4.9 years vs. 10 years, P < 0.05). Rates were 42% higher among Whites
      compared to Blacks (4.5/10(6) person-years vs. 3.1/10(6) person-years, P < 0.01).
      CONCLUSIONS: We found M/PNET is increasing in incidence and more frequent among
      Whites. Given that medulloblastoma and PNET are histologically identical and have
      similar epidemiologic profiles, future studies should provide analyses that
      combine these entities.

PMID- 12210450
TI  - Having a brain tumour: a journey through life.

PMID- 12210451
TI  - Cancer and the adolescent: the Second Teenage Cancer Trust International
      Conference, Royal College of Physicians, London, England, March 2001.

PMID- 12210452
TI  - Treatment of childhood acute lymphoblastic leukemia at a regional non-academic
      center in Belarus.
AB  - The outlook for children with cancer is improving in the less privileged nations
      of the world. This report from Belarus is representative of results that can be
      achieved.

PMID- 12210453
TI  - Medical research: why trouble the patient for informed consent?

PMID- 12210455
TI  - Outcome of B-cell non-Hodgkin lymphoma protocol CCCG-B NHL97: a report from
      Chinese multi-center cooperative group.

PMID- 12210456
TI  - Coeliac disease and ganglioneuroblastoma: an unusual association.

PMID- 12210457
TI  - Sonographic evaluation of liver nodularity: Inspection of deep versus superficial
      surfaces of the liver.
AB  - PURPOSE: We determined the diagnostic performance of assessing the nodularity of
      deep versus superficial surfaces of the liver as a predictor of cirrhosis.
      METHODS: One sonologist retrospectively reviewed the sonograms of 100 patients at
      risk for cirrhosis based on clinical data and laboratory tests. A second
      sonologist reviewed the sonograms of a subset of 25 patients to assess for inter
      reader variability, while the first sonologist re-reviewed the sonograms of a
      different subset of 25 patients for intrareader variability. Sonograms of all
      patients were obtained with standard sector- or curved-array transducers. Biopsy
      confirmation of cirrhosis was used as the standard for diagnostic accuracy.
      RESULTS: Fifty of the 100 patients had a pathologic diagnosis of cirrhosis. The
      sensitivity of inspection of the deep surface versus the superficial surface was
      86% versus 53% (p = 0.0003), respectively. Sensitivity was not dependent on
      pathologic type. Intrareader agreement was better for deep than for superficial
      surface observations. The overall inter-reader agreement was fair and comparable
      for both deep and superficial surface methods. CONCLUSIONS: The sensitivity for
      detecting cirrhosis based on surface nodularity is greater for deep than for
      superficial surface observations. As the prevalence of disease increases, the
      accuracy of assessment of the deep surface in predicting cirrhosis increases.

PMID- 12210458
TI  - Validity of sonographic screening for the detection of abdominal cancers.
AB  - PURPOSE: This study assessed the prevalence of abdominal cancers and the validity
      of sonographic screening for abdominal cancers in an asymptomatic population.
      METHODS: We investigated the findings of the first sonographic screening of
      16,024 residents of Osaka Prefecture. A comparison of records was carried out
      between the list of those screened and the Osaka Cancer Registry to identify
      false-negative results of our screening. RESULTS: The rate of subjects who
      required further testing after screening was 4.76% (762/16,024). Eleven of the
      762 subjects with a positive sonographic screening study had abdominal cancers
      detected on further testing. Three subjects had false-negative screening results.
      The positive predictive value of sonographic screening was 1.4% (11/762), and the
      rate of screening-detected cancers was 0.069% (11/16,024). The prevalence of
      abdominal cancers was 0.087% (14/16,024), the sensitivity of screening sonography
      for the detection of abdominal cancers was 78.6% (11/14), and the specificity was
      95.3% (15,259/16,010). Seven of 11 screening-detected cancers were resected
      curatively, and 6 of these patients are still alive. Five of these 6 cancers were
      renal cell carcinomas. CONCLUSIONS: The sensitivity of screening sonography was
      relatively high and the specificity was sufficient among our asymptomatic
      population. The present study suggests that the target organ for sonographic
      screening to detect curable cancers should be the kidneys.

PMID- 12210459
TI  - Sonographically guided percutaneous sclerosis using 1% polidocanol in the
      treatment of vascular malformations.
AB  - PURPOSE: The aim of this prospective study was to assess the safety and efficacy
      of sonographically guided percutaneous injection of 1% polidocanol for sclerosis
      of peripheral vascular malformations. METHODS: Patients with vascular
      malformations of soft tissues were invited to enroll in the study. Gray-scale and
      color Doppler sonography were performed to determine the texture, margins, and
      size of the lesions and to determine whether high-velocity blood flow was
      present. Using real-time sonographic guidance, lesions were punctured with a
      20/21-gauge spinal needle. When possible, venous return was occluded before
      injection. For each injection, 1-6 ml of 1% polidocanol was injected into 1 or
      more sites within the lesion. The sclerosing agent was not aspirated after
      injection. Repeat radiography was performed 1 month after each injection session.
      The procedure was repeated if the patient did not have a complete response,
      defined as an 80% or greater decrease in the volume of the lesion or resolution
      of the presenting symptoms. RESULTS: Of the 15 patients enrolled, 9 had venous
      malformations, 3 had lymphangiomas, 1 had a recurrent aneurysmal bone cyst, 1 had
      a venous pseudoaneurysm, and 1 had an arteriovenous malformation of the pinna.
      Each patient received 1-20 injections of 1% polidocanol (mean +/- standard
      deviation, 3.3 +/- 4.8 injections). This treatment resulted in a complete
      response of 7 venous malformations, 3 lymphangiomas, and the arteriovenous
      malformation and partial response of 2 venous malformations, the recurrent
      aneurysmal bone cyst, and the venous pseudoaneurysm. Only minor complications
      occurred. CONCLUSIONS: Sonographically guided percutaneous injection of 1%
      polidocanol for sclerosis of peripheral vascular lesions is simple, effective,
      and safe. This technique is especially effective in cases of soft tissue venous
      malformation and lymphangioma.

PMID- 12210460
TI  - Renal sonography in the diagnosis of renal obstruction or hydronephrosis in
      patients with cervical cancer.
AB  - PURPOSE: The aim of this prospective study was to evaluate the role of renal
      sonography and its use as an alternative to intravenous urography in detecting
      ureteral obstruction or hydronephrosis in patients with cervical cancer.
      MATERIALS AND METHODS: Patients with biopsy-confirmed carcinoma of the cervix who
      were referred to the radiotherapy center from February 6, 2001, through July 20,
      2001, were enrolled in this trial. All patients had previously undergone clinical
      staging by physical examination and either intravenous urography or CT scanning
      as the standard tests for diagnosing ureteral obstruction or hydronephrosis. All
      patients underwent renal sonography as an alternative diagnostic tool for
      diagnosing ureteral obstruction or hydronephrosis. RESULTS: Forty patients were
      enrolled. Their mean age was 46 years (range, 26-65 years). According to the FIGO
      staging system, 12% of the patients had clinical stages 1B2 and 2A disease, 20%
      had stage 2B, 8% had stage 3A, 50% had stage 3B, and 10% had a postoperative
      recurrence of cervical cancer. Thirty-four patients had had intravenous urography
      and 6 had had CT scans of the abdomen and pelvis. Sensitivity, specificity,
      positive and negative predictive values and overall accuracy rates for renal
      sonography were 76.5% (13/17), 100% (23/23), 100% (13/13), 85% (23/27), and 90%
      (36/40), respectively. Seventy-five percent (3/4) of the false-negative results
      occurred in patients with pelvic sidewall thickening on physical examination.
      CONCLUSIONS: Renal sonography may be used as an effective and relatively low-cost
      means of diagnosing ureteral obstruction in patients with cervical cancer without
      clinically evident pelvic sidewall thickening.

PMID- 12210461
TI  - Transvaginal sonography in the detection of retained products of conception after
      first-trimester spontaneous abortion.
AB  - PURPOSE: The aim of this study was to assess the use of transvaginal sonography
      to detect retained products of conception after first-trimester spontaneous
      abortion. METHODS: All women who arrived at our hospital with spontaneous first
      trimester abortions were included in this study and underwent transvaginal
      sonography. A sonographic diagnosis of "incomplete abortion" was based on a
      bilayer endometrial thickness of more than 8 mm. The final diagnosis of complete
      or incomplete abortion was based on the histopathologic findings at dilatation
      and curettage. The sensitivity and specificity of both clinical and sonographic
      examinations for detecting products of conception were assessed. RESULTS: A total
      of 113 women were recruited, and 14 were excluded for various reasons. Among 52
      women with a clinically incomplete abortion, only 50% had retained products of
      conception. The use of transvaginal sonography resulted in a 29% (15/52)
      reduction of surgical intervention in these women. On the other hand, 30% (14/47)
      of women with a clinical diagnosis of complete abortion had retained products of
      conception. The sensitivity and specificity of cervical status for detecting
      retained products of conception were 65% and 56%, respectively, whereas the
      overall sensitivity and specificity of transvaginal sonographic examination
      (bilayer endometrial thickness 8 mm or less) were 100% and 80%, respectively.
      CONCLUSIONS: Transvaginal sonography is a useful supplement to clinical
      assessment in women who experience a spontaneous first-trimester abortion. If
      this modality is used to assess the uterine cavity, the cervical status can be
      ignored. Use of transvaginal sonography should reduce unnecessary general
      anesthesia and uterine curettage.

PMID- 12210462
TI  - Sonographic detection of diffuse peripheral nerve enlargement in hereditary
      neuropathy with liability to pressure palsies.
AB  - Hereditary neuropathy with liability to pressure palsies (HNPP) is a disorder
      characterized by a tendency to develop focal neuropathies after trivial traumas.
      On teased nerve fiber studies, sausage-shaped myelin sheath swellings (tomacula)
      are found. We report the sonographic findings in a patient with genetically
      proven HNPP. We were able to demonstrate enlargement of several peripheral
      nerves, even nerves that were clinically unaffected. Enlargement was found not
      only at typical nerve entrapment sites but also outside these sites. This diffuse
      nerve enlargement may play an important role in the pathogenesis of entrapment
      neuropathies in HNPP patients.

PMID- 12210463
TI  - Giant iliopsoas bursitis: sonographic findings with magnetic resonance
      correlations.
AB  - We present the case of a 40-year-old man with rheumatoid arthritis who had a
      painless left inguinal mass. Sonographic examination revealed a large soft tissue
      mass with mixed internal echotexture and regular borders extending inside the
      pelvis and into the proximal portion of the thigh. Sonography also showed
      communication between the bursa of the iliopsoas muscle and the hip cavity, with
      intra-articular synovitis and erosion of the ileum. Giant iliopsoas bursitis
      secondary to hip involvement in rheumatoid arthritis was diagnosed on the basis
      of the sonographic findings. This diagnosis was confirmed by MRI.

PMID- 12210464
TI  - Gray-scale and color Doppler sonographic findings in a case of subacute
      granulomatous thyroiditis mimicking thyroid carcinoma.
AB  - Subacute granulomatous thyroiditis is a common disease of unknown cause and is
      usually self-limiting, with complete resolution of symptoms occurring
      spontaneously or after steroidal treatment. We report a case of subacute
      granulomatous thyroiditis in a 62-year-old woman whose clinical presentation was
      consistent with thyroid carcinoma. Gray-scale and color Doppler sonography
      revealed marked enlargement of the left lobe of the thyroid and markedly
      hypoechoic, ill-defined focal areas in both lobes. No flow was noted on color
      Doppler sonographic examination. Fine-needle aspiration of the thyroid was
      performed, and histopathologic examination of the specimen confirmed the
      diagnosis of subacute granulomatous thyroiditis. The patient received
      prednisolone therapy (20 mg/day) for 2 weeks and recovered well. This case report
      is the first to describe the gray-scale and color Doppler sonographic appearances
      of subacute granulomatous thyroiditis. This disease should be included in the
      differential diagnosis of patients with clinical signs and symptoms of thyroid
      carcinoma. Histopathologic examination is necessary to confirm the diagnosis.

PMID- 12210465
TI  - Sonographically guided percutaneous ethanol treatment of a symptomatic complex
      nodule with a large cystic component in a patient with thyroid hemiagenesis.
AB  - Thyroid hemiagenesis is a rare anomaly that is usually discovered incidentally
      during the evaluation of unrelated thyroid disorders. We present the case of a
      patient with hemiagenesis of the left thyroid lobe and a large, recurrent,
      symptomatic complex nodule with a large cystic component that occupied most of
      the right lobe. She had previously undergone multiple unsuccessful aspirations of
      the cyst. The patient was successfully treated with an intranodular injection of
      ethanol under sonographic guidance. The success of this procedure resulted in the
      resolution of symptoms and avoidance of surgical resection of the right lobe,
      with resulting hypothyroidism. We recommend that ethanol injections be considered
      for treatment of symptomatic cystic or benign solid nodules in patients with
      thyroid hemiagenesis and in those who have undergone hemithyroidectomy and have
      symptomatic nodules.

PMID- 12210466
TI  - Various Doppler sonographic appearances and challenges in prenatal diagnosis of
      vasa praevia.
AB  - Rupture of vasa praevia is associated with a high rate of fetal or neonatal
      mortality. Since the recent development of color and spectral Doppler sonography,
      prenatal diagnosis of vasa praevia has been increasing but is not yet consistent.
      We report 2 cases that were diagnosed prenatally, enabling cesarean section to be
      performed under optimal conditions to prevent complications. A better knowledge
      of the characteristic Doppler sonographic appearances and the risk factors
      associated with vasa praevia could greatly facilitate the prenatal diagnosis of
      this condition and hence the fetal prognosis.

PMID- 12210467
TI  - Clue for distinguishing hepatic arterial calcifications from pneumobilia.

PMID- 12210468
TI  - Sonographic features of diverticulitis and diverticulosis of the vermiform
      appendix.

PMID- 12210469
TI  - Potential of the hormonal hypothesis of sex ratio to explain the unusual sex
      ratios typical of some malformations.

PMID- 12210471
TI  - Reviewing old concepts at the start of a new millenium: growth restriction,
      adrenal hypoplasia, and thymomegaly in human anencephaly.
AB  - BACKGROUND: Anencephaly has been associated frequently with intrauterine growth
      retardation (IUGR), consistently with adrenal hypoplasia, and occasionally with
      an enlarged thymus. Few studies have analyzed the relationship between
      gestational age (GA), IUGR, associated anomalies and thymomegaly in anencephaly.
      The aims of our study were to evaluate this relationship and to highlight the
      usefulness of anencephaly as a model when investigating immune-endocrine
      interactions. METHODS: Fifty-two anencephalics' autopsies were reviewed
      retrospectively. Body weight, adrenal, and thymus weights were compared to
      prenatal, postnatal, and stillborn control values, and between associated and
      isolated anencephalic cases (presenting with and without other unrelated
      anomalies). Comparisons of adrenal and thymus weights were done by GA and by body
      weight. Thymus weight:body weight (TW:BW) ratios were compared to expected
      values. RESULTS: Anencephalics' body and adrenal weights were lower than their
      control values, whereas thymus weights did not differ. Body and thymus weights
      were twice as high in isolated than in associated anencephaly, whereas adrenal
      weights did not differ. Anencephalics TW:BW ratios were higher than their control
      values, higher in cases with IUGR, and higher in isolated rather than associated
      cases. When distributed by GA, thymus weights in anencephaly increased at a
      higher-than-expected rate. CONCLUSIONS: Our results suggest that adrenal
      hypoplasia is invariably present in anencephaly, and depending on an
      underdeveloped pituitary gland, seems to be independent of its etiology. On the
      contrary, IUGR mainly exists in associated cases and thymus enlargement mainly
      exists in isolated cases, suggesting a relationship with the underlying cause.

PMID- 12210472
TI  - Offspring of male and female parents with thalidomide embryopathy: birth defects
      and functional anomalies.
AB  - BACKGROUND: The aim of the study was to evaluate congenital malformations and
      functional anomalies in the offspring of Swedish parents with thalidomide
      embryopathy (TE). METHODS: Sixty-four children (29 girls, 35 boys) with ages
      ranging from 0-18 years, born to 34 Swedish parents (14 women, 20 men) with TE,
      were studied. Data on malformations and dysfunction were collected from medical
      records at maternity and child healthcare units, delivery units, hospitals,
      outpatient clinics and schools. RESULTS: Five children had both a mother and
      father with TE, 23 had a mother suffering from TE, and in 36 children the father
      had TE. One girl had a major malformation consisting of pulmonary stenosis, and
      single cases of minor physical features and positional deformities were observed.
      One boy had autism. Four children were born preterm, all to a TE mother. One
      child died within 24 hr after birth. Seven spontaneous abortions were registered,
      five of them in TE mothers. The cesarian section rate was 39% among the TE
      mothers, compared to 14% among the non-TE mothers. CONCLUSIONS: Malformations or
      functional anomalies similar to those typical for TE were not found in this group
      of children born to Swedish parents with TE. Cesarian sections were more
      frequently performed in TE mothers, partly because of pelvic and uterine
      malformations.

PMID- 12210473
TI  - Effects on toes from prenatal exposure to anticonvulsants.
AB  - BACKGROUND: Changes in the distal phalanges of the fingers, including coned
      epiphyses and hypoplasia of the phalanges, are recognized teratogenic effects of
      the anticonvulsant drugs phenytoin and phenobarbital. We hypothesized that the
      frequency of these changes would also be increased in the toes of children
      exposed to these drugs in comparison to unexposed children. METHODS: We report on
      the findings in an analysis of radiographs of the feet of 63 children exposed in
      utero to either phenytoin alone, phenobarbital alone or both drugs and 56
      unexposed comparison children. RESULTS: Only subtle changes were identified. The
      frequency of coned epiphyses and hypoplasia of phalanges of the toes was the same
      in both the anticonvulsant and unexposed children. Among the anticonvulsant
      exposed children, however, there was a strong association between the presence of
      coned epiphyses in the feet and in the hands: all five children with coned
      epiphyses in the hands, as described previously in the same individuals by Lu et
      al. ([2000] Teratology 61:277-283) had coned epiphyses in their feet (P =
      0.0012). Measurements showed a shortening of metatarsals in all three treatment
      groups, but this was significant only in the phenytoin monotherapy-exposed
      children. CONCLUSIONS: Subtle changes are present in the phalanges and
      metatarsals of the feet of anticonvulsant-exposed children, but the overall
      frequency is much less than occurred in the hands of the same children. We
      conclude that the presence of either coned epiphyses or hypoplasia of the
      phalanges of the toes cannot be considered a distinctive feature of the
      teratogenicity of the anticonvulsant drugs phenytoin and phenobarbital.

PMID- 12210474
TI  - Teratogen update: fetal effects after in utero exposure to coumarins overview of
      cases, follow-up findings, and pathogenesis.

PMID- 12210475
TI  - Androgens block interleukin-1 beta-induced promatrilysin expression in prostate
      carcinoma cells.
AB  - BACKGROUND: We have shown previously that interleukin (IL) -1 beta- and IL-6
      induced promatrilysin expression is mediated by an indirect pathway that requires
      NF kappa B-dependent synthesis of IL-6 and STAT3 signaling. We now demonstrate
      that IL-1 beta-induced but not IL-6-induced promatrilysin expression can be
      blocked by androgens in the prostate carcinoma cell line LNCaP (lymph node
      derived carcinoma cells of the prostate). METHODS: By using enzyme-linked
      immunosorbent assay analyses, promatrilysin was measured in LNCaP cells
      stimulated with IL-1 beta or IL-6 LNCaP-treated cells pretreated with
      testosterone. In addition, promatrilysin message was measured by using Northern
      analyses after IL-6-treated cells pretreated with testosterone. RESULTS: In LNCaP
      treated with testosterone before IL-1 beta stimulation induced promatrilysin
      expression was completely abrogated. Furthermore, testosterone completely
      abrogated NF kappa B transactivation activity and induction of IL-6 protein
      expression and mRNA. Testosterone and 5 alpha-dihydrotestosterone did not have an
      inhibitory effect on IL-6-induced promatrilysin expression. Testosterone also had
      no effect on basal promatrilysin expression or basal NF kappa B transactivation
      activity. CONCLUSION: From these data, we conclude that testosterone blocks IL-1
      beta-induced promatrilysin expression by inhibition of NF kappa B transactivation
      activity, which in turn, blocks IL-6 expression. These data suggest a mechanism
      in vivo by which invasive and metastatic prostatic carcinoma cell clones
      refractory to hormone ablation therapy may develop after chemical or surgical
      castration. Furthermore, these data suggest that, perhaps, upstream targets such
      as the cytokines IL-1 beta and IL-6 may provide alternative drug targets for
      inhibiting prostate cancer progression.

PMID- 12210476
TI  - Anti-tumor effects of toxins targeted to the prostate specific membrane antigen.
AB  - BACKGROUND: There is presently no effective therapy for relapsing, metastatic,
      androgen-independent prostate cancer. Immunotherapy with monoclonal antibody
      vehicled toxins (Immunotoxins, ITs) may be a promising novel treatment option for
      the management of prostate cancer in these cases. METHODS: Three anti-prostate
      specific membrane antigen (anti-PSMA) monoclonals (J591, PEQ226.5, and PM2P079.1)
      were cross-linked to ricin A-chain (RTA; native or recombinant), and their
      cytotoxic effects were investigated in monolayer and three-dimensional (3-D) cell
      cultures of prostate carcinoma cells (LNCaP). RESULTS: The various Immunotoxins
      showed effects in the nanomolar range (IC(50s) of 1.6-99 ng/ml) against PSMA+
      cells (IC(50) being the concentration inhibiting 50% cell proliferation or
      protein synthesis). PSMA(-) cell lines were 62- to 277-fold less sensitive to
      anti-PSMA ITs, evidencing an appreciable therapeutic window. Treatment with J591
      smpt-nRTA (0.35-31.7ng/ml) resulted in complete eradication of 3-D tumor
      micromasses or in 1.46- to 0.35-log reduction of target cells number, depending
      on the dose. CONCLUSION: Anti-PSMA ITs appear to be promising for use in the
      eradication of small prostate tumor cell aggregates present in tissues and in the
      bone marrow.

PMID- 12210477
TI  - Progressive prostate hyperplasia in adult prolactin transgenic mice is not
      dependent on elevated serum androgen levels.
AB  - BACKGROUND: Transgenic mice overexpressing the rat prolactin (PRL) gene under
      control of the metallothionein-1 promoter (Mt-1) develop a dramatic prostatic
      enlargement. These animals also display significantly elevated testosterone serum
      levels. In this study, we aim to clarify the role of circulating androgen levels
      in the promotion of abnormal prostate growth in the adult PRL transgenic mouse
      prostate. METHODS: Prostate morphology and androgen-receptor distribution
      patterns were analyzed in castrated and testosterone substituted adult PRL
      transgenic and in wild-type males. RESULTS: Progressive prostatic hyperplasia in
      adult PRL transgenic males was not affected by substitution to serum testosterone
      levels corresponding to wild-type. Furthermore, prolonged testosterone treatment
      in adult wild-type males did not produce any significant changes in prostate
      growth or morphology compared with wild-type controls. Immunohistochemical
      studies revealed a significantly increased proportion of androgen receptor
      positive epithelial cells in all lobes of the PRL transgenic prostate versus wild
      type. CONCLUSION: The present study demonstrates that progressive prostate
      hyperplasia in adult PRL transgenic mice is not dependent on elevated serum
      androgen levels. Furthermore, prolonged androgen treatment in adult wild-type
      male mice appears to have no significant effect on prostate growth. In addition,
      our results suggest that prolonged hyperprolactinemia results in changes in
      prostate epithelial and stromal cell androgen receptor distribution.

PMID- 12210479
TI  - Expression of somatostatin receptor subtypes 2 and 4 in human benign prostatic
      hyperplasia and prostatic cancer.
AB  - BACKGROUND: The presence of receptor subtypes for the inhibitory peptide
      somatostatin in prostatic tissue has been a controversial issue with conflicting
      reports. To elucidate whether prostatic epithelial cells express mRNA for
      somatostatin receptor (SSTR) subtype 2 and 4, we have investigated the
      localization of SSTR2 and SSTR4 transcripts in prostatic tissues by in situ
      hybridization. METHODS: Nonradioactive in situ hybridization was performed with
      specific fluorescein-labeled SSTR2 and SSTR4 riboprobes on consecutive sections
      of benign prostatic hyperplasia (BPH) and prostate cancer tissues. RESULTS: We
      report, for the first time, tissue localization of SSTR2 and SSTR4 mRNA in BPH
      and malignant cells of human prostate. Hybridization signals for SSTR4 mRNA
      transcripts were confined to the prostatic epithelium (12 of 16 BPH cases, and in
      12 of 13 carcinoma cases), whereas SSTR2 transcripts were predominantly localized
      in the stromal compartment but also were detectable in epithelial cells in a
      significant number of specimens (11 of 17 BPH cases, and in 12 of 14 carcinoma
      cases). Furthermore, the staining intensity for SSTR2 and SSTR4 transcripts is
      stronger in malignant cells compared with adjacent BPH epithelium. CONCLUSION:
      The data presented suggest that the expression of SSTR2 and SSTR4 transcripts is
      up-regulated in malignant cells and that not only SSTR2 agonists, but also
      compounds targeting the SSTR4 subtype may have a potential role in the treatment
      of prostate cancer.

PMID- 12210478
TI  - Both retinoids and androgens are required to maintain or promote functional
      differentiation in reaggregation cultures of human prostate epithelial cells.
AB  - BACKGROUND: Primary cultures and subcultures of prostate epithelial cells (PEC)
      proliferate markedly, but rapidly loose secretory differentiated function and
      androgen responsiveness. Here, we investigated whether differentiation could be
      restored or preserved by using three-dimensional reaggregation cultures treated
      with retinoids and/or androgens. METHODS: PEC were cultured as monolayers or as
      reaggregation cultures on a rotatory shaker. Reaggregation cultures were also
      developed from freshly isolated cells. Morphology was evaluated microscopically.
      Expression of cytokeratins (CKbasal for basal cells and CK18 for luminal cells),
      E-cadherin, alpha- and beta-catenin, androgen receptor (AR), and prostate
      specific antigen (PSA) was evaluated by immunohistochemistry and/or Western
      blotting. Differentiated function was further evaluated by measurements of PSA in
      the medium and by reverse transcriptase-polymerase chain reactions for AR, PSA,
      prostate specific membrane antigen, beta-microseminoprotein, and zinc-alpha 2
      glycoprotein. Proliferation was evaluated by immunohistochemical staining for Ki
      67. RESULTS: Monolayer cultures of PEC expressed CKbasal as well as CK18, a
      combination compatible with an intermediary amplifying population of epithelial
      cells. No expression of PSA could be detected, and all attempts to re-induce
      differentiation of PEC in classic two-dimensional culture systems failed. In
      reaggregation cultures of subcultured PEC, retinoids proved essential to maintain
      a compact three-dimensional structure. This effect was accompanied by increased
      levels of E-cadherin and of the catenins and by a shift in the cytokeratin
      expression pattern toward that typical for secretory differentiated cells (CK18
      only). Even in the presence of androgens, however, PSA remained undetectable.
      Similar effects of retinoids were observed in reaggregation cultures of freshly
      prepared PEC, and in the latter cultures, the combination of androgens and
      retinoids maintained a low level of PSA secretion for at least 40 days.
      CONCLUSIONS: A combination of retinoids and androgens is able to preserve, for a
      prolonged period of time, some degree of secretory differentiation in freshly
      isolated PEC maintained in reaggregation culture. The same combination is unable
      to restore secretory differentiation in subcultured PEC.

PMID- 12210480
TI  - Loss of heterozygosity at 7q31.1 and 12p13-12 in advanced prostate cancer.
AB  - BACKGROUND: Allelic losses on chromosome arms 2q, 3p, 5q, 6q, 7q, 8p, 9p, 10p,
      10q, 11p, 11q, 12p, 13q, 16q, 17p, 17q, 18q, and 21q are reportedly associated
      with progression and/or initiation of prostate cancer. In the present study, we
      performed a polymerase chain reaction (PCR) analysis of polymorphic
      microsatellite loci on the human chromosomes 7 and 12p13-12 in prostate cancer
      tissue to investigate the extent of involvement of these regions, which may
      contain putative tumor suppressor genes. METHODS: Tissue samples were obtained at
      autopsy from 17 men who died of hormone-refractory prostate cancer at Chiba
      University, Japan, and affiliated hospitals between June of 1992 and June of
      1995. DNA from normal tumor or metastatic tissue was used as the template for PCR
      amplification of a set of 16 polymorphic microsatellite loci on human chromosome
      7 and 6 loci on the human chromosome region 12p13-12. RESULTS: The frequencies of
      cases with loss of heterozygosity (LOH) at 7q31.1 were 8% in primary tumor tissue
      and 11% in metastatic tissue. The frequencies of cases with LOH at 12p13-12 were
      12% in primary tumor tissue and 25% in metastatic tumor tissue. CONCLUSIONS: In
      the present study, the frequencies of LOH at 7q31.1 were lower than in Western
      patients, suggesting that LOH in this region is not related to progression of
      prostate cancer in Japanese patients. The frequency of LOH at 12p13-12 was
      similar to that reported in Western countries, indicating that 12p13-12 may
      contain a tumor suppressor gene of prostate cancer.

PMID- 12210481
TI  - Association of the G289S single nucleotide polymorphism in the HSD17B3 gene with
      prostate cancer in Italian men.
AB  - BACKGROUND: Prostate cancer is a significant public health problem in this
      country. Substantial data support a plausible role for androgens in the etiology
      of this disease. The human HSD17B3 gene encodes the testicular (or type III) 17
      beta-hydroxysteroid dehydrogenase enzyme, which catalyzes testosterone
      biosynthesis in men. METHODS: We have investigated the G289S (glycine at codon
      289 replaced by serine) polymorphism at the HSD17B3 locus as a candidate single
      nucleotide polymorphism (SNP) for prostate cancer risk in constitutional DNA from
      103 Italian prostate cancer patients and 109 Italian disease-free centenarians to
      assess the role of this SNP in susceptibility to prostate cancer. RESULTS: The
      G289S polymorphism confers a significant increase in risk for prostate cancer
      (odds ratio = 2.5; 95% confidence interval, 1.03-6.07) in our study population.
      CONCLUSION: Our data are consistent with a plausible role of the G289S SNP in
      prostate cancer susceptibility. Therefore, the HSD17B3 gene may be a plausible
      candidate gene for prostate cancer risk.

PMID- 12210482
TI  - Fas-Fas ligand signaling pathway mediates an interleukin-12-induced rejection of
      a murine prostate tumor system.
AB  - BACKGROUND: Recent data suggest that anti-tumor activities of interleukin-12 (IL
      12) involve the induction of apoptosis. Fas (APO-1/CD95) is a type I membrane
      protein that is capable of initiating an apoptosis signaling pathway when bound
      to its ligand (FasL). We undertook this study to test the hypothesis that Fas
      FasL-mediated apoptosis plays a role in IL-12-induced tumor regression. METHODS:
      An mIL-12 expression vector driven by cytomegalovirus promoter was used to
      express murine IL-12 cDNA in the RM-9 murine prostate carcinoma cell line.
      Control RM-9 cells and RM-9 cells stably transfected with IL-12 gene (RM-9-IL12)
      were inoculated subcutaneously in 4- to 6-week-old male C57BL/J6 mice. Tumor size
      was measured every 3 days. Western blot and immunohistochemical assays were used
      to evaluate Fas and FasL protein expression. In situ fluorescent end labeling was
      used to label apoptotic cells. RESULTS: IL-12-expressing RM-9 prostate carcinoma
      cells transplanted into C57BL/J6 mice grew more slowly than control RM-9 cells
      and vector control RM-9-Luc cells. The average survival time of the RM-9-IL12
      mice was longer than 53 days, whereas the mean survival for mice transplanted
      with control RM-9 cells was only 16 days. Apoptotic cells were more numerous in
      RM-9-IL12 tumors: 10.3% vs. 1.5% in control (P = 0.001). Fas and FasL proteins
      were increased approximately twofold in the RM-9-IL12 tumors compared with the RM
      9 control tumors as determined by Western blot and immunohistochemical analyses
      (P < 0.05). CONCLUSION: The Fas-FasL-mediated apoptosis pathway may contribute to
      the IL-12-induced rejection of prostate carcinoma.

PMID- 12210483
TI  - Induction of cell cycle arrest and apoptosis in human prostate carcinoma cells by
      a recombinant adenovirus expressing p27(Kip1).
AB  - BACKGROUND: Adp27(Kip1), a recombinant adenovirus, was evaluated for expression
      of p27, a cyclin-dependent kinase inhibitor (CDKI) and tumor suppressor protein,
      in human prostate carcinoma cells. Effects of p27(Kip1) on cell cycle and
      apoptosis were analyzed. METHODS: We evaluated the effects of overexpression of
      p27(Kip1) in the human prostate carcinoma cell lines LNCaP, DU-145, and PC-3 in
      vitro and in vivo. Growth curve studies, cell cycle analysis, terminal
      deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL), and annexin V
      fluorescein isothiocyanate apoptosis analyses were conducted to determine effects
      of p27(Kip1) on cell cycle. CDKI activity assays and Western blots were conducted
      to determine presence/activities of CDKIs. RESULTS: Adp27(Kip1)-induced protein
      levels increased in a dose-dependent manner; p27(Kip1) protein was detected
      within 6 hr of infection with Adp27(Kip1) and remained stable for at least 48 hr.
      The activities of Cdk2, Cdk4, and Cdc2 kinases were inhibited 24 hr after
      infection with Adp27(Kip1). Bromodeoxyuridine incorporation demonstrated a dose
      dependent decrease in S-phase cells 24 hr postinfection. TUNEL analysis revealed
      an induction of apoptosis (10 pfu/cell) within 48 hr of infection in all cell
      lines. Growth curve analyses demonstrated that Adp27(Kip1) infection inhibited
      proliferation of all cell lines tested and decreased cell numbers for Adp27(Kip1)
      infected LNCaP and PC-3 cells by 96 hr. Cell cycle analysis of DNA content
      demonstrated an accumulation of cells in G0/G1-phase 24-120 hr after Adp27(Kip1)
      infection. In vivo studies demonstrated a reduction in LNCaP xenograft tumor
      growth rates in mice injected with Adp27(Kip1). CONCLUSION: Exogenous p27(Kip1)
      overexpression results in cell cycle regulation in the human prostate carcinoma
      cell lines tested, representing the first use of this vector on prostate cancer
      cell lines in vitro and in vivo. Moreover, p27(Kip1) expression is associated
      with an increase in early apoptosis, which represents a recently discovered
      function for this protein. It also represents the first time this association has
      been observed in prostate carcinoma cell lines. This study provides support for
      the further development of Adp27(Kip1) as a potential therapeutic vector in the
      treatment of adenocarcinoma of the prostate.

PMID- 12210484
TI  - Linkage between polymorphisms in the prostate specific antigen ARE1 gene region,
      prostate cancer risk, and circulating tumor cells.
AB  - BACKGROUND: The prostate specific antigen (PSA) gene has a polymorphic androgen
      response element (ARE) sequence with two alleles, A and G. PSA A-allele carriers
      have higher serum PSA levels in healthy men (HM). METHODS: We analysed DNA
      samples from 278 (556 alleles) unrelated individuals, 127 HM and 151 prostate
      cancer (PC) patients, for PSA ARE1 genotypes. RESULTS: The analysis of the
      frequencies from the 556 alleles indicates a significant overrepresentation of A
      allele in the PC group under the age of 67 compared with the HM group (63.3% vs.
      48.8%; P = 0.009). We found that men carrying two A-alleles have increased risk
      for PC onset under the age of 67 (odds ratio [OR] = 2.92; 95% confidence interval
      [CI], 1.10-7.86; P = 0.013). Multivariate logistic regression analysis confirmed
      this association (OR = 1.82; 95% CI, 1.03-3.22; P = 0.037). Furthermore, the
      homozygosity for the A-allele was associated with higher serum PSA levels (P =
      0.027) and with the presence of circulating tumor cells in the blood of PC
      patients (P = 0.018). CONCLUSION: Our results indicate that polymorphism in the
      PSA gene promoter may be an important biomarker for prostate cancer risk,
      especially for an earlier onset of PC.

PMID- 12210485
TI  - Enhanced expression of vimentin in motile prostate cell lines and in poorly
      differentiated and metastatic prostate carcinoma.
AB  - BACKGROUND: The metastatic potential of a series of prostate cell lines was
      analysed by measuring motility and invasiveness, and further correlated to the
      expression of epithelial differentiation markers. METHODS: Invasion and motility
      were measured using in vitro assays. Immunohistochemistry of cell lines and
      tissues was used to identify expression of cytokeratins 8 and 1, 5, 10, 14,
      vimentin, prostate specific antigen, prostate specific membrane antigen, androgen
      receptor, desmoglein, E-cadherin, beta1 integrin, CD44, hmet, vinculin and actin.
      RESULTS: Expression of vimentin was the only marker to correlate with motility,
      no markers correlated to invasion. Lower vimentin expression was observed in
      cells with low motility (PNT2-C2) and high expression in cells with high motility
      (P4E6, PNT1a, PC-3). Vimentin expression was not detected in well differentiated
      tumours, moderately differentiated tumours contained vimentin positive cells (1/9
      bone scan negative, 2/5 bone scan positive), but the majority of poorly
      differentiated cancers (4/11 bone scan negative, 9/14 bone scan positive) and
      bone metastases (7/8) had high vimentin expression in tumour cells. CONCLUSIONS:
      Motile prostate cancer cell lines express vimentin. In tissue sections, the
      presence of vimentin positive tumour cells correlated positively to poorly
      differentiated cancers and the presence of bone metastases.

PMID- 12210486
TI  - SWOG-9510: evaluation of topotecan in hormone refractory prostate cancer: a
      Southwest Oncology Group study.
AB  - BACKGROUND: Prostate cancer is the most common malignancy in American men, and as
      many as 70% of those initially treated for localized disease will ultimately
      progress and be considered candidates to receive therapy for metastatic cancer
      [Fuks et al.: Int J Radiat Oncol Bio Phys 21:537-547, 1991; Chodak et al.: N Engl
      J Med 330:246-248, 1994]. Although most will respond initially to hormone
      manipulation, essentially all will fail and require additional therapy. No
      standard chemotherapy approach has been shown to prolong survival significantly,
      and new agents are desperately needed. Topotecan is a new topoisomerase-1
      inhibitor whose early investigation suggested possible activity in hormone
      refractory prostate cancer. METHODS: In this phase II trial, patients having
      failed one or two prior androgen ablative therapies were treated with 21-day
      continuous intravenous infusions of topotecan at a dose of 0.5 mg/m(2) per day
      every 28 days. RESULTS: Twenty-six eligible patients were entered on the study.
      There were no confirmed tumor responses. Median survival was 9 months. The most
      common toxicities were hematologic, with 8 of 24 assessable patients experiencing
      grade 4 toxicity. CONCLUSION: Topotecan infusions at this dose are ineffective in
      the management of hormone-refractory prostate cancer.

PMID- 12210487
TI  - Polymorphisms in the androgen receptor and type II 5 alpha-reductase genes and
      prostate cancer prognosis.
AB  - BACKGROUND: Cytosine-adenine-guanine repeat length of the androgen receptor gene
      and the A49T and V89L polymorphisms of the 5 alpha-reductase (SRD5A2) gene have
      been associated with prostate cancer. METHODS: We investigated the relationship
      of the three genetic polymorphisms to tumor grade among 211 men who had undergone
      radical prostatectomy. Subjects had prostate cancer <3 cm(3) with a percentage of
      cancer represented by Gleason grade 4 or 5 (% Gleason grade 4/5) of either > or =
      20% or < or = 5%. We also examined the association between those genetic markers
      and prostate specific antigen (PSA) failure among 112 subjects with > or = 20%
      Gleason grade 4/5. RESULTS: In cross-sectional analysis, none of the
      polymorphisms was a significant predictor of % Gleason grade 4/5. In longitudinal
      analysis, the LL genotype at the V89L site was associated with statistically
      significant four- to sixfold increase in PSA failure risk after adjustment for
      clinicopathologic variables. CONCLUSIONS: We observed poorer prognosis among men
      with the LL genotype at codon 89 of the SRD5A2 gene. Lack of consistency between
      studies must be resolved before clinical utility of this marker is established.

PMID- 12210488
TI  - Postatrophic hyperplasia of the prostate in Japan: histologic and
      immunohistochemical features and p53 gene mutation analysis.
AB  - BACKGROUND: Postatrophic hyperplasia (PAH) is one of the patterns of prostatic
      atrophy but has been regarded as a precursor of prostatic cancer (PCA) because of
      its possible increase in proliferative activity compared with simple atrophy and
      morphologic mimicry of PCA. METHODS: Radical prostatectomy specimens obtained
      from 28 patients with PCA were analyzed by histologic and immunohistochemical
      methods by using 34 beta E12 and Ki-67 as primary antibodies. Tissue from PAH,
      PCA, high-grade prostatic intraepithelial neoplasia (HGPIN), a possible precursor
      of PCA, and benign hyperplasia were microdissected and p53 gene mutations were
      examined by the polymerase chain reaction-single strand conformation polymorphism
      method followed by direct sequencing. RESULTS: Histologically, PAH consists of
      compactly arranged small acini with irregular atrophic-appearing contours,
      mimicking PCA. PAH lesions were detected in 7 (25%) of 28 cases with PCA:
      multifocal in 6 of 7 (85.7%) cases, maximum size of lesions ranged from 0.3 to
      2.3 mm. Mild nuclear enlargement and small nucleoli were observed in all cases.
      Capsular or perineural invasion, crystalloids, and mitotic figures were not found
      in any case. Inflammatory changes and fibrosis near PAH were found in 100% and
      71% of cases, respectively. PAH involved non-transition zone in all cases and
      occasionally involved transition zone. Forty-three percent of PAH lesions were in
      proximity (<2 mm) to PCA. None of the clinical and pathologic factors examined
      were correlated with the presence of PAH. Immunohistochemical analysis by using
      34 beta E12 revealed intact basal cells. Proliferative activity defined by
      positive rate for labeling with MIB-1 antibody was intermediate between benign
      prostatic hyperplasia and HGPIN. The frequency of p53 mutations in PAH lesions
      was 5.3%, which was similar to that in HGPIN lesions (4.2%). Benign glands never
      showed mutations. CONCLUSION: These findings suggested that PAH might be a
      precursor for PCA.

PMID- 12210489
TI  - Prediagnostic toenail cadmium and zinc and subsequent prostate cancer risk.
AB  - BACKGROUND: Cadmium is a recognized human lung carcinogen that has also been
      positively associated with prostate cancer mainly in occupationally exposed men.
      The association between dietary and supplemental zinc intake and prostate cancer
      has not been consistent in epidemiologic studies. We evaluated the association
      between prediagnostic toenail cadmium and zinc concentrations and risk of
      prostate cancer in a cohort in which the primary route of exposure to cadmium and
      zinc is the diet. METHODS: Included in the analysis were 115 prostate cancer
      cases and 227 age-matched controls nested in the prospective CLUE II study
      located in Washington County, MD. Participants provided toenail samples at
      baseline in 1989. Furnace atomic absorption and flame atomic absorption were used
      to determine toenail cadmium and zinc concentrations, respectively. Odds ratios
      (OR) and 95% confidence intervals (CI) were estimated from conditional logistic
      regression models. RESULTS: Median toenail cadmium and zinc concentrations did
      not statistically significantly differ between prostate cancer cases (cadmium,
      45.9 ppb; zinc, 155.3 ppm) and controls (cadmium, 54.5 ppb; zinc, 164.0 ppm).
      Prostate cancer risk did not increase with increasing concentrations of cadmium
      (P trend = 0.9) and did not decrease with increasing concentrations of zinc (P
      trend = 0.2). For both metals, the ORs for the top four fifths were each below
      1.0 when compared with the bottom fifth. CONCLUSION: Men who have high toenail
      cadmium concentrations in the range observed in this general population sample
      were not at an increased risk for prostate cancer. Although there was no evidence
      of a linear dose-response, these findings suggest that risk of prostate cancer
      may be slightly lower among men with moderate and higher zinc intake.

PMID- 12210490
TI  - Does amount or type of alcohol influence the risk of prostate cancer?
AB  - BACKGROUND: Prostate cancer is one of the most common cancers among men, and it
      is unknown whether alcohol is associated with the development of prostate cancer.
      METHODS: The relationship between amount or type of alcohol and prostate cancer
      was studied in a pooled prospective setting conducted from 1976 to 1994 in
      Copenhagen, Denmark. The study population consisted of 12,989 subjects drawn from
      three different cohorts. During a mean follow-up of 12.3 yr, 233 subjects
      developed prostate cancer. RESULTS: None of the estimates for consumed amount of
      total alcohol diverged significantly from unity. Furthermore, drinkers of more
      than 13 beers, 13 glasses of wine, and 13 drinks of spirits had a risk of 1.03
      (CI: 0.67, 1.60), 0.92 (CI: 0.42, 1.99), and 1.01 (CI: 0.52, 1.98), respectively,
      compared with abstainers of the given beverage of alcohol. CONCLUSION: These
      results suggest that neither amount nor type of alcohol is associated with the
      risk of prostate cancer.

PMID- 12210491
TI  - Mutational analysis of ETV6 in prostate carcinoma.
AB  - BACKGROUND: In an effort to better understand the molecular events responsible
      for progression of prostate carcinoma to metastatic disease, we have recently
      identified a homozygous deletion at 12p12-13 involving ETV6 (tel). Although
      mutational analysis of ETV6 has not been examined previously in prostate
      carcinoma, it is an attractive candidate prostate cancer tumor suppressor gene
      since as it previously has been implicated in malignancy. Therefore, we decided
      to analyze 43 prostate cell lines, xenografts, and metastatic foci for
      inactivating mutations. METHODS: DNA was isolated from 7 cell lines, 18
      xenografts, and 18 metastatic deposits. Single-strand conformational polymorphism
      (SSCP) analysis of ETV6, was performed by polymerase chain reaction (PCR)
      amplification of each exon by using intron specific primers. PCR products were
      then resolved by gel electrophoresis, and aberrantly migrating PCR products were
      then sequenced. RESULTS: Two previously described polymorphisms and four novel
      sequence changes were identified. Polymorphisms at nucleotide 258 (G --> A, Thr -
      > Thr) and 602 (T --> C, Leu --> Pro) were identified in eight and one
      specimen(s), respectively. Analysis of noncancerous DNA confirmed the presence of
      the polymorphisms in the germ-line. Four possible mutations were identified at
      nucleotides 24 (T --> G, Cys --> Trp), 380 (G --> A, Arg --> Glu), 776 (G --> T,
      Arg --> Leu), and 876 (C --> T, Leu --> Leu). Three were in xenografts or cell
      lines. Because normal DNA was not available, these could represent rare
      polymorphisms. The sole mutation in a clinical specimen, at nucleotide 876, did
      not result in an amino acid change. CONCLUSION: Our data suggest that mutational
      inactivation ETV6 may occur in prostate carcinoma. The functional significance of
      these potential inactivating mutations remains to be determined.

PMID- 12210492
TI  - Direct effect of zinc on mitochondrial apoptogenesis in prostate cells.
AB  - BACKGROUND: Prostate epithelial cells uniquely accumulate significantly higher
      levels of zinc than other mammalian cells. We previously showed that the
      accumulation of high intracellular zinc levels in specific prostate cells results
      in the induction of apoptosis and the inhibition of cell growth. The apoptotic
      effect is due to zinc induction of mitochondrial apoptogenesis. We now report
      additional studies that corroborate this effect of zinc and provide insight into
      the mechanism of this unique effect. METHODS: The effect of exposure to
      physiological levels of zinc on apoptosis was determined for three human prostate
      cell lines (PC-3, BPH, and HPR-1). Zinc-induced apoptosis was identified by DNA
      fragmentation. The direct effect of zinc on isolated mitochondrial preparations
      from each cell line was determined. The mitochondrial release of cytochrome c was
      determined by Western blot. RESULTS: Exposure to zinc induced apoptosis in PC-3
      and BPH cells but not in HPR-1 cells. The zinc accumulation in PC-3 (4.3 +/- 0.3)
      and BPH (2.8 +/- 0.4) was higher than that in HPR-1 cells (1.8 +/- 0.1). The
      apoptotic effect of zinc on PC-3 cells could be observed as early as 4-6 hr of
      zinc treatment, and this effect was not reversible. The exposure of isolated
      mitochondria from PC-3 and BPH cells to zinc resulted in the release of
      cytochrome c; but zinc had no effect on mitochondria from HPR-1 cells.
      CONCLUSIONS: Exposure to zinc induces apoptosis in PC-3 and BPH cells, which
      accumulate high intracellular levels of zinc, but not in HPR-1 cells, which do
      not accumulate high levels of zinc. Once initiated, the induction of apoptosis is
      not reversed by the removal of zinc, i.e., it is an irreversible process. The
      apoptogenic effect is due to a direct effect of zinc on mitochondria that results
      in the release of cytochrome c. The cell specificity of zinc induction of
      apoptogenesis is dependent on the ability of the cells to accumulate high levels
      of intracellular zinc and on the ability of the mitochondria to respond to the
      direct effect of zinc.

PMID- 12210493
TI  - Resveratrol induces apoptosis in LNCaP cells and requires hydroxyl groups to
      decrease viability in LNCaP and DU 145 cells.
AB  - BACKGROUND: This study was conducted to determine the effects of resveratrol on
      prostate cancer cell viability through apoptosis induction and the significance
      of the three hydroxyl groups on resveratrol to the measured effect. METHODS:
      Hormone-sensitive LNCaP cells and hormone-insensitive DU 145 cells were treated
      with resveratrol, tri-methoxy-resveratrol, or diethylstilbestrol (DES; the
      positive control for toxicity and apoptosis). Cell viability was determined by
      using an MTS assay. Apoptosis was determined by the appearance of apoptotic
      morphology, annexin V-FITC-positive intact cells, and caspase activation.
      RESULTS: Resveratrol and DES decreased viability in LNCaP cells, but only
      resveratrol-treated cells expressed apoptotic morphology, annexin V-FITC-positive
      cells, and caspase activation. Tri-methoxy-resveratrol had no effect on DU 145
      cell-viability and was less toxic to LNCaP cells than resveratrol. CONCLUSION:
      Resveratrol was toxic to cells regardless of whether the cells were hormone
      responsive or -unresponsive. This finding suggests that the cell's hormone
      responsive status is not an important determinant of the response to resveratrol.
      Furthermore, the hydroxyl-groups on resveratrol are required for cell toxicity.
      Finally resveratrol but not DES induced caspase-mediated apoptosis.

PMID- 12210494
TI  - Fetotoxicity caused by the interaction between zinc and arsenic in mice.
AB  - Arsenic is an environmental pollutant that induces congenital malformations in
      experimental models and can contribute to human birth defects. The environmental
      exposure to arsenic is relatively small when compared with the doses required to
      cause teratogenicity in mice and other laboratory animals. In order to study the
      action of zinc in the arsenic-induced teratogenicity, in the present work mice
      were either pretreated with zinc and later with arsenic or were treated
      simultaneously with zinc and arsenic in vivo and in vitro. Following
      administration of arsenate on gestation day 8, pregnant females were killed on
      the 17th day of gestation; maternal and fetal data were collected by laparotomy
      and used to calculate reproductive parameters. Fetuses were analyzed for the
      presence of external malformation and, after the appropriate processing, visceral
      and skeletal analyses were accomplished. Conceptuses were exposed in whole embryo
      culture to arsenicals on gestation day 8 (3-6 somite stage). After a 26 h culture
      period, morphological development was assessed. Neither pretreatment with zinc
      nor simultaneous administration of zinc prevented arsenic teratogenicity in these
      experimental models.

PMID- 12210496
TI  - Rat ventral prostate microsomal biotransformation of ethanol to acetaldehyde and
      1-hydroxyethyl radicals: its potential contribution to prostate tumor promotion.
AB  - Rat ventral prostate microsomal fraction was able to biotransform ethanol to
      acetaldehyde and 1-hydroxyethyl radicals (1HEt) in the presence of NADPH and
      oxygen. The enzymatic processes involved were not inhibited by desferrioxamine,
      CO, SKF 525A, 4-methylpyrazole, or polyclonal antibody against P450 reductase but
      they were significantly inhibited by diethyldithiocarbamate, 2-mercapto-1
      methylimidazol, thiobenzamide, or diphenyleneiodonium chloride. Results would
      suggest the partial participation in these ethanol bioactivation processes of
      flavin containing monooxygenase (FMO) and/or other flavin dependent
      oxidases/peroxidases and of a non-iron metal-containing enzymes. Acetaldehyde and
      free radicals production by prostate microsomal fraction might potentially
      contribute to tumor promotion in heavy alcohol drinkers.

PMID- 12210495
TI  - Effects of glucose on cloning efficiency and mutagenesis of fetal rat cells.
AB  - In a previous study, treatment of rats with 10% glucose in the drinking water, as
      fetuses during gestation and for 1.5 months after delivery, significantly
      enhanced tumor incidence that resulted from N-methyl-N-nitrosourea (MNU, 20
      mg/kg) given transplacentally on gestation day 21, with a 1.6-fold increase in
      overall tumor incidence. We investigated whether glucose would have an effect on
      MNU-induced mutation in fetal F-344 rat somatic cells as measured in an in
      vivo/in vitro assay. Rat fetuses were exposed transplacentally to MNU on
      gestation day 16 and to a 10% glucose solution from gestation day 7 to day 17.
      Cells were isolated on gestation day 17 for determination of cloning efficiency
      and for selection of 6-thioguanine (6-TG)-resistant HGPRT mutants. Cloning
      efficiency of the fetal cells exposed to MNU alone was 22.6+/-2.3% S.E., while
      that for cells from fetuses exposed to MNU+glucose was 27.5+/-1.6% S.E., which
      was a significant difference (P=0.018). This indicates an effect of glucose on
      cell proliferation and survival. MNU treatment significantly increased the
      mutation frequency of fetal cells from a spontaneous value of 0.4 x 10(-6) per
      viable cell to (8.8+/-1.8 S.E.,) x 10(-6) (P=0.0087). The coexposure to MNU and
      glucose yielded a mutant frequency per plate of 0.62+/-0.05 S.E., which was a 1.5
      fold increase compared to MNU alone (0.43+/-0.11 S.E., P=0.075. In summary, the
      data indicate that glucose during pregnancy increases proliferation/survival of
      fetal cells and possibly also mutation rate.

PMID- 12210497
TI  - DNA-PK inhibitor wortmannin enhances DNA damage induced by bleomycin in V79
      Chinese hamster cells.
AB  - The fungal metabolite wortmannin (WM) is a potent and irreversible inhibitor of
      the enzyme DNA-dependent protein kinase (DNA-PK), a nuclear serine-threonine
      kinase, member of the phosphaditylinositol-3 kinase related kinase family. WM has
      been used in the last few years as a promising radiosensitizer mainly throughout
      cell survival experiments. However, few studies have addressed the role of DNA-PK
      inhibition in the repair of DNA lesions generated by antitumor agents. Bleomycin
      (BLM) is an antitumor agent used in the treatment of various neoplasia with a
      unique genotoxicity profile that mimics the ionizing radiation effects. In this
      study, we evaluated the effect of different concentrations of WM on the DNA
      damage induced by BLM. The cytokinesis-block micronucleus assay (CBMN) in V79
      Chinese hamster cells was used as the end-point. WM significantly increased the
      frequency of micronucleated cells (%MNBN) by about 2.2-fold, the number of
      micronuclei per binucleated cell (MN/BN) by about 2.4-fold, and also changed the
      pattern of the distribution of micronuclei induced by BLM. The frequency of
      micronucleated cells with 2 MN per cell and with > or = 3 MN per cell increased,
      whereas the frequency of micronucleated cells with 1 MN per cell decreased. WM
      was not genotoxic but decreased cell proliferation as assessed by the frequency
      of binucleated cells. Our results show that WM clearly enhances the efficacy of
      BLM in terms of DNA damage inflicted and therefore reinforces its use as a
      chemosensitizer.

PMID- 12210498
TI  - Inhibitory effects of ascorbic acid and folinic acid on chromosome aberrations
      induced by pyrimethamine in vitro.
AB  - In this study, the anticlastogenic effects of ascorbic acid and the protective
      effect of folinic acid against the formation of chromosomal aberrations in humans
      by pyrimethamine were investigated. Pyrimethamine is a folic acid antagonist used
      for the treatment of malaria and toxoplasmosis. In this study, 18 different
      healthy people, who do not drink alcohol and are non-smokers, were chosen as an
      experimental group; 0.025 mg/ml pyrimethamine was given to the lymphocyte
      culture, which had been prepared with the peripheral blood taken from this group.
      After that each of the following doses were given to the same culture: 20, 40,
      and 80 mM of ascorbic acid and 25, 50, and 100 mM of folinic acid. The results of
      the cytogenetic evaluation showed that the aberrations due to pyrimethamine in
      the chromosomes were reduced by ascorbic acid and folinic acid significantly,
      depending on the given dose.

PMID- 12210499
TI  - Teratogenic effects of N-ethyl-N-nitrosourea (ENU) on larvae of the self
      fertilizing fish Rivulus marmoratus (Cyprinodontiformes, Rivulidae).
AB  - We showed that N-Ethyl-N-Nitrosourea (ENU) induces teratogenesis in larvae of the
      self-fertilizing fish Rivulus marmoratus. We discuss this and the issue of
      carcinogenesis caused by ENU.

PMID- 12210500
TI  - Determination of allelic deletion of multiple endocrine neoplasm type 1 (MEN1)
      gene in acute myeloid leukemia (AML) by application of FISH-TSA technique.
AB  - We have used the single and dual color fluorescence in situ hybridization (FISH)
      technique combined with a new detection system, tyramide signal amplification
      (TSA), by using the multiple endocrine neoplasm type 1 (MEN1) gene and chromosome
      11 specific alpha satellite DNA probes for the study of the allelic deletion of
      the MEN1 gene. The MEN1 gene is a new tumor suppressor gene and has been recently
      cloned on chromosome 11q13. FISH combined with the TSA detection system was
      performed on bone marrow interphase nuclei of 22 patients with acute myeloid
      leukemia (AML). The FISH-TSA analysis revealed the mono allelic deletion of the
      MEN1 gene in 4 out of 22 patients (18.18%), 2 of 9 AML-M2 patients (22.2%), 1 of
      6 AML-M4 patients (16.6%), and 1 of 4 AML-M5 patients (25.0%). Our study
      indicates that allelic deletion of the MEN1 gene is not a major cause or a
      primary event in tumorigenesis of AML, although the long arm (q13 region) of
      chromosome 11 involves a chromosomal rearrangement in AML.

PMID- 12210501
TI  - Blocking the translation elongation factor-1 delta with its antisense mRNA
      results in a significant reversal of its oncogenic potential.
AB  - In spite of the strong evidence for the carcinogenic activity of cadmium and its
      related compounds, the underlying molecular mechanisms that lead to malignant
      transformation in cells exposed to cadmium remain unknown. Recently, Joseph et
      al. [J. Biol. Chem. 227:6131-6136, 2002] have identified, cloned, and
      characterized the mouse Translation Elongation Factor-1 delta sub-unit (TEF-1
      delta, GenBank Accession Number AF304351) as a novel cadmium-responsive proto
      oncogene. Presently, additional studies regarding the oncogenic potential of TEF
      1 delta have been carried out. Transfection of NIH3T3 cells with the pcDNA3.1
      expression vector containing the TEF-1 delta cDNA in the sense (5'-->3')
      orientation resulted in overexpression of the encoded 31 kDa protein.
      Transfection-mediated overexpression of TEF-1 delta protein resulted in
      transformation of the cells as evidenced from the appearance of transformed foci.
      Cotransfection of the cells with a mixture of plasmid DNA consisting of TEF-1
      delta cDNA in the sense (5'-->3') and in the antisense (3'-->5') orientation
      resulted in significant inhibition of translation of the TEF-1 delta protein.
      Antisense TEF-1 delta mRNA-mediated inhibition of translation of TEF-1 delta
      protein, furthermore, resulted in inhibition of TEF-1 delta-mediated
      transformation of NIH3T3 cells as evidenced from the decrease in the number of
      transformed foci. These results further confirm that overexpression of TEF-1
      delta is oncogenic and the antisense TEF-1 delta mRNA expression reverses its
      oncogenic potential.

PMID- 12210502
TI  - Genetic polymorphisms in the cytochrome P450 1A1, glutathione S-transferase M1
      and T1, and susceptibility to colon cancer.
AB  - Several polymorphic cytochrome P-450 and glutathione S-transferase (GST) enzymes
      are involved in the activation and detoxification of many potential carcinogens
      and may therefore be important in susceptibility to cancer induction. CYP1A1
      MspI, GSTM1, and GSTT1 are polymorphic enzymes and some alleles have been
      correlated with an increased risk of developing some cancers. In the present
      study, we examined possible associations between genetic polymorphisms of CYP1A1
      MspI, GSTM1, and GSTT1 and colon cancer in a United Kingdom population. An excess
      of CYP1A1 MspI, and GSTM1 null genotypes was observed amongst colon cancer
      patients, although this did not reach the level of statistical significance. We
      found no significant increase in the risk of colon cancer for either CYP1A1 MspI
      (OR = 1.39; 95%CI: 0.46-4.21) or GSTM1 null (OR = 1.41; 95%CI: 0.76-3.01)
      genotypes. Individuals with GSTT1 null genotype had no association with colon
      cancer (OR = 0.42; 95%CI: 0.09-2.02). No significant association was observed in
      the site of colon cancer (proximal vs. distal). This study suggests that the
      polymorphisms of CYP1A1 MspI, GSTM1, and GSTT1 are not associated with a
      significant risk of developing colon cancer in a United Kingdom population.

PMID- 12210503
TI  - Mass spectrometric detection in chromatography. Trends and perspectives.
AB  - The newest results in the use of miscellaneous mass spectrometric detection
      methods in various chromatographic techniques are compiled and critically
      evaluated. Examples of application in clinical chemistry, health care, and in the
      analysis of pharmaceuticals, environmental pollutants, foods and food products
      are given. The benefits and drawbacks of MS detection are discussed, and future
      trends are briefly discussed.

PMID- 12210504
TI  - On-Line HPLC-UV-mass spectrometry and tandem mass spectrometry for the rapid
      delineation and characterization of differences in complex mixtures: a case study
      using toxic oil variants.
AB  - An integrated differential approach to the characterization of complex mixtures
      is presented which includes the targeting of liquid chromatography (LC) peaks for
      identification using characteristic UV adsorption of the LC peak, subsequent
      molecular weight and formula determination using accurate mass LC mass
      spectrometry (MS), and structure characterization using accurate mass LC-tandem
      mass spectrometry. The use of differential UV adsorption aids in narrowing the
      scope of the study to only specific peaks of interest. Accurate mass measurement
      of the molecular ion species provides molecular weight information as well as
      atomic composition information. The tandem MS (MS/MS) spectra provide
      fragmentation information which allows for structural characterization of each
      component. Accurate mass assignment of each of the fragment ions in the MS/MS
      spectrum provides atomic composition for each of the fragment ions and thus
      further aids in the structural characterization. These experiments are
      facilitated through the use of on-line LC-MS and LC-MS/MS with in-line UV
      detection. A synthetic toxic oil (STO) related to Toxic Oil Syndrome is studied
      with a focus on possible contaminants resulting from the interaction of aniline,
      used as a denaturant, with the normal components of the oil. A differential
      analysis between the STO and a control oil is performed. LC peaks were targeted
      using UV absorbance to indicate the possible presence of the aniline moiety.
      Further differential analysis was performed through the determination of the MS
      signals associated with each component separated on the LC. Finally, the MS/MS
      data was also used to determine if the fragmentation of the targeted components
      indicated the presence of aniline. The MS/MS and accurate mass data were used to
      assign the structures for the targeted components.

PMID- 12210505
TI  - Determination of bisphenol A in rat brain by microdialysis and column switching
      high-performance liquid chromatography with fluorescence detection.
AB  - A sensitive column switching HPLC-fluorescence detection for determination of
      bisphenol A (BPA) in rat brain by coupling with microdialysis was developed. A
      microdialysis probe was inserted into the hypothalamus of rat brain and an
      artificial cerebrospinal fluid was used for perfusion. BPA in brain dialysate was
      subjected to a fluorescent derivatization with 4-(4,5-diphenyl-1H-imidazol-2
      yl)benzoyl chloride (DIB-Cl), and the excess reagent was removed by a column
      switching technique. Separation was carried out on two ODS semimicro-columns with
      the mobile phase of acetonitrile-H(2)O-methanol-tetrahydrofuran (55:10:35:2.5,
      v/v) and acetonitrile-0.1 M acetate buffer (pH 3.0)-methanol (35:10:55, v/v) at a
      flow rate of 0.10 and 0.15 mL/min for a precolumn and a separation column,
      respectively. Fluorescence intensity was monitored at 475 nm with excitation of
      350 nm. BPA could be sensitively detected at 0.3 ppb in 60 micro L brain
      microdialysate at a signal-to-noise ratio of 3. By the proposed method,
      concentrations of BPA in rat brain and plasma were monitored for 8 h after single
      i.v. or oral administration. It is proved that BPA is capable of penetrating the
      blood-brain barrier. The ratio of the area under the concentration-time curve of
      BPA in rat brain to that in blood was estimated to be about 3.0-3.8%.

PMID- 12210506
TI  - Capillary electrophoresis of Cr(VI) reducer Arthrobacter oxydans.
AB  - Rapid and effective separation of bacteria Arthrobacter oxydans was performed
      using capillary electrophoresis. For optimal separation of bacteria the influence
      of buffer concentration, pH and applied voltage were studied. It was found that
      the most appropriate conditions for electrophoretic mobility measurements are as
      follows: applied voltage 6-14 kV; buffer concentration 5-10 mM pH 6-8. At the
      stationary phase of growth there are always two main heterogeneous peaks. They
      are connected with the morphology of bacteria as well as with cell aggregation.
      The heterogeneity of samples may be explained by surface modifications of
      bacterial cells.

PMID- 12210507
TI  - Preliminary observations on the influence of rheumatoid alpha-1-acid glycoprotein
      on collagen fibril formation.
AB  - This study investigates the effect of alpha(1)-acid glycoprotein (AGP) isolated
      from both normal and rheumatoid plasma on type II collagen fibril formation.
      Rheumatoid samples were obtained over 2 years from two patients with early
      arthritis. The glycosylation of each sample was analysed to establish any
      correlation with fibrillogenesis. Rheumatoid AGP displays increased fucosylation
      compared to normal AGP. In both patients the fucosylation dipped after 1 year,
      then rose again over year 2. It is proposed that year 1 corresponds to the acute
      phase of the disease and the onset of chronic inflammation after this time
      produces a subsequent increase in fucosylation. Rheumatoid AGP influences type II
      collagen fibrillogenesis. Native fibrils were produced but with differences in
      the rate and extent of fibrillogenesis depending on AGP concentration and
      fucosylation. Low concentrations produced a decrease in fibrillogenesis rate and
      fibril diameter. High concentrations produced fibrils at a rate and diameter
      dependent on fucosylation. Highly fucosylated AGP produced narrow fibrils slowly,
      whereas poorly fucosylated AGP produced thicker fibrils more quickly. We propose
      that differences in glycosylation (especially fucosylation) of AGP are
      responsible for differences in collagen fibrillogenesis and this phenomenon may
      contribute to the exacerbation of cartilage destruction in rheumatoid arthritis.

PMID- 12210508
TI  - LC-ESI-MS analysis of taxoids from the bark of Taxus wallichiana.
AB  - LC-ESI-MS analysis was carried out for taxoid profiling of partially purified
      methanol extracts of the stem bark of Taxus wallichiana growing in different
      regions of the Himalayas (Kashmir, Himachal Pradesh, UP hills, Sikkim and
      Arunachal Pradesh). Cone voltage fragmentation of the protonated, ammonium or
      sodium cationized molecular species resulted in diagnostic fragment ions. Thus,
      information about the number and nature of substituents and the taxane skeleton
      (whether it is normal or rearranged) was readily available from the LC-ESI-MS
      spectra. The rearranged 11(15-->1)-abeo-taxanes showed a characteristic
      elimination of the hydroxyisopropyl along with an acetoxy group. The
      identification of the taxoids was achieved by comparison of the ESI mass spectra
      with those of the authentic taxoids available to us or by interpreting the ESI
      mass spectra. The results were also corroborated by MS/MS analysis of the
      partially purified extract injected directly into the ESI source. Paclitaxel, its
      analogues and their xylosides are present in samples from all the regions. An
      interesting observation is the detection of a large number of basic taxoids
      having nitrogen-containing side chains.

PMID- 12210509
TI  - Liquid chromatographic resolution of gemifloxacin mesylate on a chiral stationary
      phase derived from crown ether.
AB  - A new racemic fluoroquinolone antibacterial agent, gemifloxacin mesylate, has
      been successfully resolved on a chiral stationary phase (CSP) derived from (+)
      (18-crown-6)-2,3,11,12-tetracarboxylic acid. Compared to the Crownpak CR(+)
      column, the CSP used in this study was more effective for the resolution of
      racemic gemifloxacin mesylate, especially in terms of analytical time. The
      resolution of gemifloxacin mesylate enantiomers on the CSP was found to be
      dependent on the type and content of organic and acidic modifiers in the aqueous
      mobile phase and the column temperature.

PMID- 12210510
TI  - Toremifene metabolism in rat, mouse and human liver microsomes: identification of
      alpha-hydroxytoremifene by LC-MS.
AB  - The in vitro metabolism of toremifene has been studied in liver microsomal
      preparations from rat, mouse and human sources using high-performance liquid
      chromatography-electrospray ionisation mass spectrometry (HPLC-ESIMS). The
      metabolites detected were N-desmethyltoremifene (m/z 392), 4-hydroxytoremifene
      (m/z 422), 4'-hydroxytoremifene (m/z 422) and toremifene N-oxide m/z 422). In
      addition, a new polar metabolite with a protonated molecule at m/z 422 has been
      detected in all three species. The compound was identified by tandem MS-MS as
      alpha-hydroxytoremifene, an analogue of alpha-hydroxytamoxifen. The results
      showed that alpha-hydroxylation is a common feature of tamoxifen and toremifene
      metabolism and that alpha-hydroxytamoxifen is unlikely to be the reactive
      metabolite responsible for the hepatocarcinogenesis in rat, as widely believed.

PMID- 12210511
TI  - What can humans learn from flies about adenomatous polyposis coli?
AB  - Somatic or inherited mutations in the adenomatous polyposis coli (APC) gene are a
      frequent cause of colorectal cancer in humans. APC protein has an important tumor
      suppression function to reduce cellular levels of the signaling protein beta
      catenin and, thereby, inhibit beta-catenin and T-cell-factor-mediated gene
      expression. In addition, APC protein binds to microtubules in vertebrate cells
      and localizes to actin-rich adherens junctions in epithelial cells of the fruit
      fly Drosophila (Fig. 1). Very little is known, however, about the function of
      these cytoskeletal associations. Recently, Hamada and Bienz have described a
      potential role for Drosophila E-APC in cellular adhesion, which offers new clues
      to APC function in embryonic development, and potentially colorectal adenoma
      formation and tumor progression in humans.

PMID- 12210512
TI  - Functional evolution of Hox proteins in arthropods.
AB  - It is presumed that the evolution of morphological diversity in animals and
      plants is driven by changes in the developmental processes that govern
      morphology, hence basically by changes in the function and/or expression of a
      defined set of genes that control these processes. A large body of evidence has
      suggested that changes in developmental gene regulation are the predominant
      mechanisms that sustain morphological evolution, being much more important than
      the evolution of the primary sequences and functions of proteins. Recent reports
      challenge this idea by highlighting functional evolution of Hox proteins during
      the evolutionary history of arthropods.

PMID- 12210513
TI  - When machines get stuck--obstructed RNA polymerase II: displacement, degradation
      or suicide.
AB  - The severe hereditary progeroid disorder Cockayne syndrome is a consequence of a
      defective transcription-coupled repair (TCR) pathway. This special mode of DNA
      repair aids a RNA polymerase that is stalled by a DNA lesion in the template and
      ensures efficient DNA repair to permit resumption of transcription and prevent
      cell death. Although some key players in TCR, such as the Cockayne syndrome A
      (CSA) and B (CSB) proteins have been identified, the exact molecular mechanism
      still remains illusive. A recent report provides new unexpected insights into TCR
      in yeast. The identification and characterisation of a novel protein co-purifying
      with the yeast homologue of CSB (Rad26) imposes reassessment of our current
      understanding of TCR in yeast. What about humans?

PMID- 12210514
TI  - Non-stop decay--a new mRNA surveillance pathway.
AB  - Gene expression is an inherently complex process and errors often occur during
      the transcription and processing of mRNAs. Several surveillance mechanisms have
      evolved to check the fidelity at each step of mRNA manufacture. Two recent
      reports describe the identification of a novel pathway in eukaryotes that
      recognizes and degrades mRNAs that lack a stop codon. The non-stop decay
      mechanism releases ribosomes stalled at the 3' end of a mRNA and stimulates the
      exosome to rapidly degrade the transcript.

PMID- 12210515
TI  - Epithelial barrier function: assembly and structural features of the cornified
      cell envelope.
AB  - Terminally differentiating stratified squamous epithelial cells assemble a
      specialized protective barrier structure on their periphery termed the cornified
      cell envelope (CE). It is composed of numerous structural proteins that become
      cross-linked by several transglutaminase enzymes into an insoluble macromolecular
      assembly. Several proteins are involved in the initial stages of CE assembly, but
      only certain proteins from a choice of more than 20 different proteins are used
      in the final stages of CE reinforcement, apparently to meet tissue-specific
      requirements. In addition, a variable selection of proteins may be upregulated in
      response to genetic defects of one of the CE proteins or tissue injury, in an
      effort to maintain an effective barrier. Additionally, in the epidermis and hair
      fiber cuticle, a layer of lipids is covalently attached to the proteins, which
      provides essential water barrier properties. Here we describe our current
      understanding of CE structure, a possible mechanism of its assembly, and various
      disorders that cause a defective barrier.

PMID- 12210516
TI  - Canonical and non-canonical Wnt signaling pathways in Caenorhabditis elegans:
      variations on a common signaling theme.
AB  - Wnt glycoproteins are signaling molecules that control a wide range of
      developmental processes in organisms ranging from the simple metazoan Hydra to
      vertebrates. Wnt signaling also plays a key role in the development of the
      nematode C. elegans, and is involved in cell fate specification and determination
      of cell polarity and cell migration. Surprisingly, the first genetic studies of
      Wnt signaling in C. elegans revealed major differences with the established
      (canonical) Wnt signaling pathways of Drosophila and vertebrates. Thus, the Wnt
      dependent induction of endoderm in the early embryo and the specification of
      several asymmetric cell divisions during larval development are mediated by as
      yet novel Wnt signaling pathways that repress, rather than activate the TCF/LEF-1
      transcription factor POP-1. Recently, however, it has been shown that, in
      addition to these divergent Wnt pathways, C. elegans also has a canonical Wnt
      pathway that converts POP-1 into an activator and controls the expression of
      several homeobox genes. Interestingly, these different Wnt pathways use distinct
      beta-catenins to control POP-1 function: the endoderm induction pathway requires
      the beta-catenin WRM-1 and parallel input from a mitogen-activated kinase (MAPK)
      pathway to downregulate POP-1, whereas the canonical Wnt pathway employs the beta
      catenin BAR-1 to activate Wnt target gene expression.

PMID- 12210517
TI  - Secreted Frizzled-related proteins: searching for relationships and patterns.
AB  - Secreted Frizzled-related proteins (SFRPs) are modulators of the intermeshing
      pathways in which signals are transduced by Wnt ligands through Frizzled (Fz)
      membrane receptors. The Wnt networks influence biological processes ranging from
      developmental cell fate, cell polarity and adhesion to tumorigenesis and
      apoptosis. In the five or six years since their discovery, the SFRPs have emerged
      as dynamically expressed proteins able to bind both Wnts and Fz, with distinctive
      structural properties in which cysteine-rich domains from Fz- and from netrin
      like proteins are juxtaposed. The abundant expression of SFRP genes in the early
      embryo, altered expression patterns in disease states, and potential significance
      in the evolution of the vertebrate body plan, make these intriguing molecules
      relevant to investigations in diverse fields of biology and biomedical sciences.

PMID- 12210519
TI  - Protosilencers as building blocks for heterochromatin.
AB  - DNA repetitions may provoke heterochromatinization. We explore here a model in
      which multiple cis-acting sequences that display no silencing activity on their
      own (protosilencers) may cooperate to establish and maintain a heterochromatin
      domain efficiently. Protosilencers, first defined in budding yeast, have now been
      found in a wide range of genomes where they appear to stabilize and to extend the
      propagation of heterochromatin domains. Strikingly, isolated or moderately
      repeated protosilencers can also be found in promoters where they participate in
      transcriptional activation and have insulation functions. This suggests that the
      proper juxtaposition of a threshold number of protosilencers converts them from
      neutral or transactivating elements into ones that nucleate heterochromatin.
      Interactions might be transient or permanent, and are likely to occur over
      distances by looping. This model provides a conceptual framework for as varied
      phenomena as telomere-driven silencing in Drosophila, X inactivation in mammals,
      and rDNA silencing in S. cerevisiae. It may also account for the silencing that
      occurs when multiple copies of a transgene are inserted in tandem.

PMID- 12210518
TI  - Molecular control of neuronal migration.
AB  - Our understanding of neuronal migration has been advanced by multidisciplinary
      approaches. At the cellular level, tangential and radial modes of neuronal
      migration contribute to different populations of neurons and have differential
      dependence on glial cells. At the molecular level, extracellular guidance cues
      have been identified and intracellular signal transduction pathways are beginning
      to be revealed. Interestingly, mechanisms guiding axon projection and neuronal
      migration appear to be conserved with those for chemotactic leukocytes.

PMID- 12210520
TI  - Beyond structure: do intermediate filaments modulate cell signalling?
AB  - Intermediate filament (IF) proteins form the largest family of cytoskeletal
      proteins in mammalian cells. The function of these proteins has long been thought
      to be only structural. However, this single function does not explain their
      diverse tissue- and differentiation-specific expression patterns. Evidence is now
      emerging that IF also act as an important framework for the modulation and
      control of essential cell processes, in particular, signal transduction events.
      Here, we review the most recent developments in this growing and exciting new
      field.

PMID- 12210521
TI  - Quiet please, do not disturb: a hypothesis of embryo metabolism and viability.
AB  - This review uses nutritional markers of normal and impaired development to
      address the question; what makes a viable mammalian preimplantation embryo?
      Resolution of this question is important to ensure the long-term safety of embryo
      based biotechnologies in man and domestic animals, the optimisation of embryo
      production and culture conditions and the development of methods to select viable
      embryos for replacement. After considering the nutrition of embryos and somatic
      cells, and the phenomenon of caloric restriction, it is concluded that
      preimplantation embryo survival is best served by a relatively low level of
      metabolism; a situation achieved by reducing the concentrations of nutrients in
      culture media and encouraging the use endogenous resources.

PMID- 12210522
TI  - The modulator is a constitutive enhancer of a developmentally regulated sea
      urchin histone H2A gene.
AB  - Going back to the late 1970s and early 1980s, we trace the Xenopus oocyte
      microinjection experiments that led to the emergence of the concept of
      "modulator". The finding that the modulator could transactivate transcription
      from far upstream and in either orientation suggested that a new genetic element,
      different from the classical prokaryotic promoter sequences, had been discovered.
      This particular enhancer transactivates transcription of the sea urchin early
      (alpha) histone H2A gene which is regulated in early sea urchin development. We
      summarise the data from sea urchin microinjection experiments that confirm and
      extend the results obtained with Xenopus oocytes. We conclude that the H2A
      enhancer is bipartite, is located approx. 100 bp upstream of the TATAAATA box in
      the H2A gene of two sea urchin species and enhances transcription when placed at
      a position far upstream or far downstream of the gene unless an insulator
      intervenes between enhancer and promoter. Evidence from microinjection
      experiments with sea urchin embryos suggests that the developmental control of
      H2A expression resides not with the enhancer, which is constitutively active, but
      with a striking chromatin structure with two positioned nucleosomes near the 3'
      end of the gene. Within this structure, there is an insulator element.

PMID- 12210523
TI  - Nucleotide sequence-based typing of bacteria and the impact of automation.
AB  - DNA-based typing methods are increasingly important for the characterisation of
      bacteria. They are used to monitor the epidemiology of pathogens with public
      health significance and also to help understand the evolution and population
      biology of bacteria. However, these methods require accuracy and reproducibility
      and are often of a high-throughput nature. Laboratory automation is therefore the
      key to the successful implementation of such methods. This review describes the
      impact of automation on DNA-based typing methods, particularly multi-locus
      sequence typing (MLST), and the method components that can be automated.

PMID- 12210526
TI  - Mitochondrial dysfunction and Down's syndrome.
AB  - Neither the pathogenesis nor the aetiology of Down's syndrome (DS) are clearly
      understood. Numerous studies have examined whether clinical features of DS are a
      consequence of specific chromosome 21 segments being triplicated. There is no
      evidence, however, that individual loci are responsible, or that the oxidative
      damage in DS could be solely explained by a gene dosage effect. Using astrocytes
      and neuronal cultures from DS fetuses, a recent paper shows that altered
      metabolism of the amyloid precursor protein and oxidative stress result from
      mitochondrial dysfunction.1 These findings are consistent with considerable data
      implicating the role of the mitochondrial genome in DS pathogenesis and
      aetiology.

PMID- 12210527
TI  - Potential genetic variance and the domestication of maize.
AB  - Since Darwin, there has been a long and arduous struggle to understand the source
      and maintenance of natural genetic variation and its relationship to phenotype.
      The reason that this task is so difficult is that it requires integration of
      detailed, and as yet incomplete, knowledge from several biological disciplines,
      including evolutionary, population, and developmental genetics. In this 'post
      genomic' era, it is relatively easy to identify differences in the DNA sequence
      between individuals. However, the task remains to delineate how this abundant
      genetic diversity actually contributes to phenotypic diversity. This necessitates
      tackling the problem of hidden genetic variation. Genetic polymorphisms can be
      conditionally cryptic, but have the potential to contribute to phenotypic
      variation in particular genetic backgrounds or under specific environmental
      conditions. A recent paper by Lauter and Doebley highlights the contribution of
      hidden genetic variation to traits characterizing the morphological evolution of
      modern maize from its wild grass-like progenitor teosinte.1 This work is the
      first to demonstrate hidden variance for selected (agronomically 'adaptive')
      traits in a well-characterized model for morphological evolution.

PMID- 12210528
TI  - Adherens junctions: new insight into assembly, modulation and function.
AB  - Adherens junctions play pivotal roles in cell and tissue organization and
      patterning by mediating cell adhesion and cell signaling. These junctions consist
      of large multiprotein complexes that join the actin cytoskeleton to the plasma
      membrane to form adhesive contacts between cells or between cells and
      extracellular matrix. The best-known adherens junction is the zonula adherens
      (ZA) that forms a belt surrounding the apical pole of epithelial cells. Recent
      studies in Drosophila have further illuminated the structure of adherens
      junctions. Scaffolding proteins encoded by the stardust gene are novel components
      of the Crumbs complex, which plays a critical role in ZA assembly.1-3 The small
      GTPase Rap1 controls the symmetric re-assembly of the ZA after cell division.4
      Finally, the asymmetric distribution of adherens junction material regulates
      spindle orientation during asymmetric cell division in the sensory organ lineage.

PMID- 12210529
TI  - The Fox and the thyroid: the amphioxus perspective.
AB  - The evolutionary origins of several vertebrate organs are still controversial.
      The thyroid is classically thought to derive directly from the endostyle (a
      pharyngeal organ found in urochordates, cephalochordates and lampreys). Several
      molecular and biochemical lines of evidence agree with this scenario. However, a
      recent paper,1 describing the expression of a FoxE ortholog in amphioxus,
      suggests that some molecular pathways might actually have been recruited from an
      adjacent region of the pharynx. Although additional data from urochordates and
      lamprey are needed to confirm this hypothesis; these results propose an
      interesting new scenario for thyroid evolution that involved the reorganisation
      of genetical and morphological features in the pharyngeal endoderm in order to
      give rise to a entirely new organ. They also give an indication that the
      ancestral role of the FoxE gene family was probably limited to the
      differentiation of part of the pharynx.

PMID- 12210530
TI  - Regulation by transcription attenuation in bacteria: how RNA provides
      instructions for transcription termination/antitermination decisions.
AB  - Regulation of gene expression by premature termination of transcription, or
      transcription attenuation, is a common regulatory strategy in bacteria. Various
      mechanisms of regulating transcription termination have been uncovered, each can
      be placed in either of two broad categories of termination events. Many
      mechanisms involve choosing between two alternative hairpin structures in an RNA
      transcript, with the decision dependent on interactions between ribosome and
      transcript, tRNA and transcript, or protein and transcript. In other examples,
      modification of the transcription elongation complex is the crucial event. This
      article will describe and compare several of these regulatory strategies, and
      will cite specific examples to illustrate the different mechanisms employed.

PMID- 12210531
TI  - Non-neural adult stem cells: tools for brain repair?
AB  - Stem cells isolated from adult mammalian tissues may provide new approaches for
      the autologous treatment of disease and tissue repair. Although the potential of
      adult stem cells has received much attention, it has also recently been brought
      into question. This article reviews the recent work describing the ability of non
      hematopoietic stem cells derived from adult bone marrow to form neural
      derivatives and their potential for brain repair. Earlier transplantation
      experiments imply that grafted adult stem cells can differentiate into neural
      derivatives. Recent reports suggest, however, that such findings may be
      misleading and grafted cells acquiring different identities may merely be
      explained by their fusion with host cells and not the result of radical changes
      to their program of cellular differentiation. Nonetheless, in vitro studies have
      shown that neural development by bone-marrow-derived stem cells also appears
      possible. Understanding the molecular mechanisms that specify the neural lineage
      will lead to the development of tools for the targeted production of neural cell
      types in vitro that may ultimately provide a source of material to treat specific
      neurological deficits.

PMID- 12210532
TI  - Radiation-induced chromosome aberrations: insights gained from biophysical
      modeling.
AB  - Enzymatic misrepair of ionizing-radiation-induced DNA damage can produce large
      scale rearrangements of the genome, such as translocations and dicentrics. These
      and other chromosome exchange aberrations can cause major phenotypic alterations,
      including cell death, mutation and neoplasia. Exchange formation requires that
      two (or more) genomic loci come together spatially. Consequently, the
      surprisingly rich aberration spectra uncovered by recently developed techniques,
      when combined with biophysically based computer modeling, help characterize large
      scale chromatin architecture in the interphase nucleus. Most results are
      consistent with a picture whereby chromosomes are mainly confined to territories,
      chromatin motion is limited, and interchromosomal interactions involve mainly
      territory surfaces. Aberration spectra and modeling also help characterize DNA
      repair/misrepair mechanisms. Quantitative results for mammalian cells are best
      described by a breakage-and-reunion model, suggesting that the dominant
      recombinational mechanism during the G(0)/G(1) phase of the cell cycle is non
      homologous end-joining of radiogenic DNA double strand breaks. In turn, better
      mechanistic and quantitative understanding of aberration formation gives new
      insights into health-related applications.

PMID- 12210533
TI  - Common structural features of nucleic acid polymerases.
AB  - Structures of multisubunit RNA polymerases strongly differ from the many known
      structures of single subunit DNA and RNA polymerases. However, in functional
      complexes of these diverse enzymes, nucleic acids take a similar course through
      the active center. This finding allows superposition of diverse polymerases and
      reveals features that are functionally equivalent. The entering DNA duplex is
      bent by almost 90 degrees with respect to the exiting template-product duplex. At
      the point of bending, a dramatic twist between subsequent DNA template bases
      aligns the "coding" base with the binding site for the incoming nucleoside
      triphosphate (NTP). The NTP enters through an opening that is found in all
      polymerases, and, in most cases, binds between an alpha-helix and two catalytic
      metal ions. Subsequent phosphodiester bond formation adds a new base pair to the
      exiting template-product duplex, which is always bound from the minor groove
      side. All polymerases may undergo "induced fit" upon nucleic acid binding, but
      the underlying conformational changes differ.

PMID- 12210534
TI  - The colonial urochordate Botryllus schlosseri: from stem cells and natural tissue
      transplantation to issues in evolutionary ecology.
AB  - The urochordates, whose stem groups may have included the direct predecessors of
      the chordate line, serve as an excellent model group of organisms for a variety
      of scientific disciplines. One taxon, the botryllid ascidian, has emerged as the
      model system for studying allorecognition; this work has concentrated on the
      cosmopolitan species Botryllus schlosseri. Studies analyzing self-nonself
      recognition in this colonial marine organism point to three levels of
      allorecognition, each associated with different outcomes. The first level
      controls natural allogeneic rejections and fusions, in which blood-shared
      chimeras are formed. The second level leads to morphological resorption of
      partners within chimeras while the third allows the development of somatic and
      germ cell parasitic events. Recent studies on multi-chimeric entities formed in
      allogeneic fusions reveal evolutionary links between allorecognition, stem cell
      biology and ecology. Thus, the Botryllus system generates perspectives from
      different biological disciplines to yield a unique life history portrait.

PMID- 12210535
TI  - Conformational control through translocational regulation: a new view of
      secretory and membrane protein folding.
AB  - We suggest a new view of secretory and membrane protein folding that emphasizes
      the role of pathways of biogenesis in generating functional and conformational
      heterogeneity. In this view, heterogeneity results from action of accessory
      factors either directly binding specific sequences of the nascent chain, or
      indirectly, changing the environment in which a particular domain is synthesized.
      Entrained by signaling pathways, these variables create a combinatorial set of
      necessary-but-not-sufficient conditions that enhance synthesis and folding of
      particular alternate, functional, conformational forms. We therefore propose that
      protein conformation is productively regulated by the cell during translocation
      across the endoplasmic reticulum (ER), a concept that may account for currently
      poorly understood aspects of physiological function, natural selection, and
      disease pathogenesis.

PMID- 12210536
TI  - Going malignant: the hypoxia-cancer connection in the prostate.
AB  - The metabolic organization of both normal and malignant prostate cellular
      phenotypes involves some unusual and surprising features. In particular, both
      conditions exhibit ratios of NADH/NAD+ and NADPH/NADP+ characteristic of high
      oxidative states despite a chronic shortage of O2 in both conditions. In this
      paper, we observe that, in prostate cancer cells, the oxidizing power of the
      fatty acid synthesis (FAS) pathway is so large that redox is stabilized more
      favorably (more oxidized) than in normal prostate cells. This FAS-facilitated
      redox improvement occurs despite the fact that malignant cells are more O2
      limited and therefore express more hypoxia inducible factor 1 (HIF1) and express
      hypoxia-regulated genes more robustly. This unusual metabolic situation clearly
      separates direct regulatory effects of redox balance from secondary effects of
      hypoxia per se. The physiological significance of the FAS pathway is thus the
      harnessing of its oxidizing power for improving redox balance despite conditions
      of more extreme hypoxia. Similar hypoxia defense strategies are found in animal
      species that are unusually tolerant to oxygen lack. Our hypothesis is that the
      metabolic organization in the "low zinc, low citrate" phenotype reflects an
      hypoxia-defense adaptation geared toward redox balance, with prostate cancer
      cells being relatively more oxidized, even if more hypoxic, than normal prostate
      cells. Recognition and understanding of these redox balancing and hypoxia defense
      functions may lead to new intervention strategies by developing new intracellular
      targets for prostate cancer therapy.

PMID- 12210537
TI  - Fluorescence correlation spectroscopy for the detection and study of single
      molecules in biology.
AB  - The recent development of single molecule detection techniques has opened new
      horizons for the study of individual macromolecules under physiological
      conditions. Conformational subpopulations, internal dynamics and activity of
      single biomolecules, parameters that have so far been hidden in large ensemble
      averages, are now being unveiled. Herein, we review a particular attractive
      solution-based single molecule technique, fluorescence correlation spectroscopy
      (FCS). This time-averaging fluctuation analysis which is usually performed in
      Confocal setups combines maximum sensitivity with high statistical confidence.
      FCS has proven to be a very versatile and powerful tool for detection and
      temporal investigation of biomolecules at ultralow concentrations on surfaces, in
      solution, and in living cells. The introduction of dual-color cross-correlation
      and two-photon excitation in FCS experiments is currently increasing the number
      of promising applications of FCS to biological research.

PMID- 12210538
TI  - Oestrogenic activity of isobutylparaben in vitro and in vivo.
AB  - The alkyl esters of p-hydroxybenzoic acid (parabens) are used widely as
      preservatives in foods, pharmaceuticals and cosmetics to which the human
      population is exposed. Recent studies have reported that methylparaben,
      ethylparaben, n-propylparaben and n-butylparaben all possess oestrogenic activity
      in several in vitro assays and in animal models in vivo. This study reports on
      the oestrogenic activity of isobutylparaben in a panel of assays in vitro and in
      vivo. Isobutylparaben was able to displace [(3)H]oestradiol from cytosolic
      oestrogen receptor alpha of MCF7 human breast cancer cells by 81% at 100 000-fold
      molar excess. Using a clonal line of MCF7 cells containing a stably transfected
      oestrogen-responsive ERE-CAT reporter gene, CAT gene expression could be
      increased by isobutylparaben such that the magnitude of the response was the same
      at 10(-5) M isobutylparaben as with 10(-8) M 17beta-oestradiol. Isobutylparaben
      could also increase expression of the endogenous oestrogen-responsive pS2 gene in
      MCF7 cells and maximal expression at 10(-5) M isobutylparaben could be inhibited
      with the anti-oestrogen ICI 182 780. The proliferation of two oestrogen-dependent
      human breast cancer cell lines MCF7 and ZR-75-1 could be increased with
      isobutylparaben such that at concentrations of 10(-5) M the proliferation
      response was of the same magnitude as with 10(-8) M 17beta-oestradiol. Evidence
      for oestrogen receptor mediation of proliferation effects was provided by the
      inability of isobutylparaben to influence the growth of oestrogen-unresponsive
      MDA-MB-231 human breast cancer cells and by the ability of the anti-oestrogen ICI
      182 780 to inhibit the isobutylparaben effects on MCF7 cell growth. The
      proliferation response to 10(-10) M 17beta-oestradiol was not antagonized with
      isobutylparaben at any concentration from 10(-9) M to 10(-4) M in either MCF7 or
      ZR-75-1 cells. Finally, subcutaneous administration of isobutylparaben was able
      to increase the uterine weight in the immature mouse after three daily doses of
      1.2 or 12.0 mg per mouse. Previous work using linear-alkyl-chain parabens has
      shown that oestrogenic activity increases with alkyl chain length from
      methylparaben to n-butylparaben. The results here show that branching of the
      alkyl chain to isobutylparaben increases oestrogenic activity beyond that of the
      equivalent length linear alkyl chain in n-butylparaben.

PMID- 12210539
TI  - Subchronic toxicity of chloral hydrate on rats: a drinking water study.
AB  - The subchronic toxicity of chloral hydrate, a disinfection byproduct, was studied
      in rats following 13 weeks of drinking water exposure. Male (262 +/- 10 g) and
      female (190 +/- 8 g) Sprague-Dawley rats, ten animals per group, were
      administered chloral hydrate via drinking water at 0.2, 2, 20 and 200 ppm.
      Control animals received distilled water only. Gross and microscopic
      examinations, serum chemistry, hematology, biochemical analysis, neurogenic amine
      analysis and serum trichloroacetic acid (TCA) analysis were performed at the end
      of the treatment period. Bronchoalveolar fluids were collected at necropsy and
      urine specimens were collected at weeks 2, 6 and 12 for biochemical analysis. No
      treatment-related changes in food and water intakes or body weight gains were
      observed. There were no significant changes in the weights of major organs.
      Except for a mild degree of vacuolation within the myelin sheath of the optic
      nerves in the highest dose males, there were no notable histological changes in
      the tissues examined. Statistically significant treatment-related effects were
      biochemical in nature, with the most pronounced being increased liver catalase
      activity in male rats starting at 2 ppm. Liver aldehyde dehydrogenase (ALDH) was
      significantly depressed, whereas liver aniline hydroxylase activity was
      significantly elevated in both males and females receiving the highest dose. A
      dose-related increase in serum TCA was detected in both males and females
      starting at 2 ppm. An in vitro study of liver ALDH confirmed that chloral hydrate
      was a potent inhibitor, with an IC(50) of 8 micro M, whereas TCA was weakly
      inhibitory and trichloroethanol was without effect. Analysis of brain biogenic
      amines was conducted on a limited number (n = 5) of male rats in the control and
      high dose groups, and no significant treatment-related changes were detected.
      Taking into account the effect on the myelin sheath of male rats and the effects
      on liver ALDH and aniline hydroxylase of both males and females at the highest
      dose level, the no-observed-effect level (NOEL) was determined to be 20 ppm or
      1.89 mg kg(-1) day(-1) in males and 2.53 mg kg(-1) day(-1) in females. This NOEL
      is ca. 1000-fold higher than the highest concentration of chloral hydrate
      reported in the municipal water supply.

PMID- 12210540
TI  - Mineral deficiency and the use of the FETAX bioassay to study environmental
      teratogens.
AB  - The Frog Embryo Teratogenesis Assay: Xenopus (FETAX) bioassay has been employed
      extensively to screen compounds for teratogenic activity. Recent laboratory
      studies have indicated that low potassium concentrations retard Xenopus laevis
      development. The effects of varying concentrations of minerals on Xenopus laevis
      embryo length and development were examined to determine the utility of the FETAX
      bioassay in the study of environmental teratogens. Water samples collected from
      18 wetlands in Minnesota and North Dakota correlated with low mineral levels,
      causing delayed embryonic development in the FETAX bioassay. When the
      concentration of sodium or potassium was <5 ppm, Xenopus laevis development was
      delayed. As a result, it was difficult to assess teratogenic activity after 96 h
      of incubation. Furthermore, the length of the embryos-an indication of
      development-paralleled changes in mineral composition. Comparisons between
      different wetlands based on changes in one specific mineral were not possible due
      to a synergism between various minerals. If the concentration of sodium and/or
      potassium was <5 ppm but > or =2 ppm, extension of the FETAX bioassay to 120 h
      allowed organogenesis to proceed through stage 46, as required for scoring in
      accordance with ASTM guidelines for the FETAX bioassay. In those cases in which
      the concentration of sodium and/or potassium were <2 ppm, the embryos could not
      develop to stage 46 within 120 h and the FETAX bioassay was not suitable for
      detecting teratogenic activity. Published in 2002 by John Wiley & Sons, Ltd.

PMID- 12210541
TI  - Approaches to the assessment of toxicity data with endpoints related to endocrine
      disruption.
AB  - There has been a substantial proliferation in the number of studies reporting
      endocrine effects as an endpoint. The vast majority have focused on
      oestrogenicity in vitro but, with recent recommendations by the USEPA Endocrine
      Disrupter Screening and Testing Advisory Committee, tests are now being developed
      for (anti)-androgenicity and effects on the thyroid, largely because of the
      potential for altering reproduction or development via these mechanisms. Despite
      being a vital organ and involved in reproduction and development, there is
      currently no provision for assessing adrenocortical function. Similarly, the
      entire process of steroidogenesis poses multiple molecular targets for toxic
      disruption that are not included in current test strategies and at present there
      is no clear position on the significance of the data being generated. This review
      provides a framework for approaching endocrine data: that all the glands,
      tissues, receptors, transporter proteins and enzymes that comprise the endocrine
      system are targets for toxicity. They should be considered in much the same way
      as other target organs, with appropriate provision for the special cases of
      carcinogenesis and teratogenesis, and a pragmatic weight of evidence approach
      should be adopted considering all available data and recognizing its limitations.
      In this approach, structure-activity relationships and in vitro and targeted in
      vivo screens provide useful data but repeat-dose regulatory studies with defined
      endpoints provide the most powerful tools for hazard assessment. Pragmatic
      consideration should be given to exposure issues (which may highlight the
      practical irrelevance, for example, of very low potency oestrogens) and
      subsequently whether endocrine disruption is the critical or most sensitive
      endpoint for a compound. Finally, endocrine disruption may be considered a
      mechanism and, as with other toxic endpoints, knowledge of effect and no
      observable-effect levels and reversibility is as important as identifying the
      target tissue or any inherent hormone-like property.

PMID- 12210542
TI  - Assessment of genome damage in a population of Croatian workers employed in
      pesticide production by chromosomal aberration analysis, micronucleus assay and
      Comet assay.
AB  - The widespread use of pesticides suggests that the evaluation of their
      genotoxicity should be extended using the different assays available. In the
      present study we used two standard cytogenetic methods (chromosomal aberration
      analysis and micronucleus assay) and the Comet assay as a relatively new and
      powerful technique. The study included 10 workers occupationally exposed to a
      complex mixture of pesticides (atrazine, alachlor, cyanazine, 2,4
      dichlorophenoxyacetic acid, malathion) during their production and 20 control
      subjects with no history of exposure to any physical or chemical agents. For the
      chromosomal aberration analysis, whole blood was cultivated for 48 h, whereas for
      the micronucleus assay, whole blood was cultivated for 72 h. For the comet assay
      whole blood was embedded in agarose on a microscope slide, lysed with detergent,
      denaturated and subjected to alkaline electrophoresis. Damage to DNA was
      evaluated by measuring tail length and calculating the tail moment. A
      significantly increased number of chromatid and chromosome breaks, as well as the
      presence of dicentric chromosomes and chromatid exchanges in exposed subjects
      compared with control subjects (P < 0.05), was found. There was also a
      statistically significant difference in frequency and distribution of micronuclei
      between the two groups examined. In the exposed subjects the Comet assay showed a
      statistically significant (P < 0.001) increase in DNA migration. Results suggest
      that long-term occupational exposure to pesticides could cause genome damage in
      somatic cells and therefore may represent a potential hazard to human health.

PMID- 12210543
TI  - Protection from half-mustard-gas-induced acute lung injury in the rat.
AB  - The chemical warfare agent analog, 2-chloroethyl ethyl sulfide, known as 'half
      mustard gas' (HMG), is less toxic and less of an environmental hazard than the
      full molecule and has been shown to produce an acute lung injury in rats when
      instilled via intrapulmonary injection. This injury is characterized by massive,
      localized hemorrhage and edema into the alveolar compartment and can be
      quantitated by measuring extravasation of (125)I-bovine serum albumin into the
      extravascular compartment. Employing this rat model of HMG-induced lung injury,
      we observed significant attenuation of the pulmonary injury when experimental
      animals were complement or neutrophil depleted prior to HMG challenge.
      Significant protection also was provided by the use of antioxidants such as
      catalase, dimethyl sulfoxide, dimethyl thiourea, resveratrol and N-acetyl-L
      cysteine (NAC). The last compound showed protection from lung injury as high as
      70% and was still effective even when given up to 90 min after exposure of the
      lungs to HMG. These data suggest that acute lung injury caused by exposure to HMG
      may be related partially to complement mediated pathways and the generation by
      neutrophils of toxic oxygen species The data indicate that NAC is an effective
      antidote against HMG-induced acute lung injury in the rat.

PMID- 12210544
TI  - Pathophysiological responses following phosgene exposure in the anaesthetized
      pig.
AB  - This study aimed to develop a reproducible model of phosgene-induced lung injury
      in the pig to facilitate the future development of therapeutic strategies. Ten
      female young adult large white pigs were used. Following induction of anaesthesia
      using a halothane/oxygen/nitrous oxide mixture, arterial and venous catheters
      were inserted together with a pulmonary artery thermodilution catheter, and a
      suprapubic urinary catheter by laparotomy. Anaesthesia was maintained throughout
      the experiment by intravenous infusion of ketamine, midazolam and alfentanil. On
      completion of surgery the animals were allowed to equilibrate for 1 h and then
      were divided into two groups. Group 1 (n = 5) was exposed to phosgene for 10 min
      (mean Ct = 2443 +/- 35 mg min m(-3)) while spontaneously breathing, whereas
      control animals (Group 2 n = 5) were exposed to air. At 30 min post-exposure,
      anaesthesia was deepened in order to allow the initiation of intermittent
      positive pressure ventilation and the animals were monitored for up to 24 h.
      Cardiovascular and respiratory parameters were monitored every 30 min and blood
      samples were taken for arterial and mixed venous blood gas analysis and clinical
      chemistry. A detailed post-mortem and histopathology was carried out on all
      animals following death or euthanasia at the end of the 24-h monitoring period.
      Control animals (Group 2) all survived until the end of the 24-h monitoring
      period with normal pathophysiological parameters. Histopathology showed only
      minimal passive congestion of the lung. Following exposure to phosgene (Group 1)
      there was one survivor to 24 h, with the remainder dying between 16.5 and 23 h
      (mean = 20 h). Histopathology from these animals showed areas of widespread
      pulmonary oedema, petechial haemorrhage and bronchial epithelial necrosis. There
      was also a significant increase in lung wet weight/body weight ratio (P < 0.001).
      During and immediately following exposure, a transient decrease in oxygen
      saturation and stroke volume index was observed. From 6 h there were significant
      decreases in arterial pH (P < 0.01), P(a)O(2) (P < 0.01) and lung compliance (P <
      0.01), whereas oxygen delivery and consumption was reduced from 15 h onwards in
      phosgene-exposed animals. Mean pulmonary artery pressure of phosgene-exposed
      animals was increased from 15 h post-exposure, with periods of increased
      pulmonary vascular resistance index being recorded from 9 h onwards. We have
      developed a reproducible model of phosgene-induced lung injury in the
      anaesthetized pig. We have followed changes in cardiovascular and pulmonary
      dynamics for up to 24 h after exposure in order to demonstrate evidence of
      primary acute lung injury from 16 h post-exposure. Histopathology showed evidence
      of widespread damage to the lung and there was also a significant increase in
      lung wet weight/body weight ratio (P < 0.001).

PMID- 12210545
TI  - Evaluation of genotoxic damage of cadmium chloride in peripheral blood of
      suckling Wistar rats.
AB  - The aim of this study was to evaluate possible genotoxic damage of cadmium
      chloride exposure in suckling rats by means of the comet assay and the in vivo
      micronucleus test of rat blood lymphocytes, because no information is available
      on the genotoxic effect of cadmium in rats at this early age. Pups were receiving
      cadmium (as CdCl(2).H(2)O) orally in fractions of 0.5 mg for 9 days, totalling
      4.5 mg Cd kg(-1) body wt, or were given a single subcutaneous injection of 0.5 mg
      Cd kg(-1) body wt. Some pups in both exposed groups were receiving calcium
      supplement (CaHPO(4).2H(2)O) in feed to reduce the body load of cadmium. Control
      pups did not receive either cadmium or calcium supplement. Cadmium in the carcass
      and organs was measured by atomic absorption spectrometry. The results showed
      that the cadmium body burden was significantly lower when the animals were
      receiving calcium supplements along with oral cadmium. The results of the
      micronucleus and comet assays showed significant differences between the control
      and exposed groups, regardless of the route of cadmium administration. The only
      statistically significant difference between the two exposed groups (oral cadmium
      and oral cadmium + calcium supplements) was in the number of micronuclei. The
      results of the comet assay showed that tail length differed statistically only
      between the control and all exposed groups, regardless of the route of cadmium
      administration. It can be concluded that the applied cadmium doses caused
      detectable genome damage but it was lower in calcium-treated pups receiving
      cadmium orally.

PMID- 12210547
TI  - Purification and characterization of two forms of methanol dehydrogenases from a
      marine methylotroph.
AB  - Two methanol dehydrogenases (MDHs), MDH1 and MDH2, were purified from a marine
      methylotroph, Methylophaga sp. strain 1. Both enzymes had very similar
      properties, including the same native molecular weight, sizes of subunits and
      substrate specificity. The N-terminal amino acid sequence of the alpha-subunit of
      MDH2 differed from that of MDH1 by having a histidine residue at a highly
      conserved glutamate position, but both sequences showed approximately 50%
      homology to the alpha-subunits of other MDHs. MDH1 had higher specific activity
      than MDH2 with respect to methanol and ethanol as a substrate. The two enzymes
      did not appear to be isoforms but that either MDH1 or MDH2 could be a mutant
      arising from spontaneous mutation.

PMID- 12210546
TI  - Estimation of growth inhibition by copper and cadmium in heavy metal tolerant
      actinomycetes.
AB  - A new isothermic model of actinomycetes growth in presence of toxic
      concentrations of Cd(2+) and Cu(2+) is described. Microbial growth inhibition,
      displayed as a decrease of biomass, can be correlated with the increase of
      cadmium(II) or copper(II) concentration in the medium. The reciprocal dry biomass
      against metal concentration showed a linear correlation higher than 0.9 in tested
      strains. The mathematical model can be useful to predict the behavior of
      actinomycetes at inhibitory concentrations of copper(II) and cadmium(II) in large
      screening procedures.

PMID- 12210548
TI  - Extracellular enzymatic activities of Bipolaris sorokiniana isolates.
AB  - Several enzymatic activities were investigated in six isolates of the fungus
      Bipolaris sorokiniana, originating from different areas of Brazil. Among the
      glycosidases studied, beta-glucosidase, beta-N-acetylglucosaminidase, beta
      xylosidase, cellobiohydrolase, and chitobiohydrolase were the major activities.
      In some isolates, beta-glucuronidase, beta-galactosidase, and alpha-mannosidase
      activities were also present. Polysaccharide-hydrolyzing enzymes, such as pectin
      lyase and carboxymethyl cellulase were detected in significant amounts, and their
      activities were variable among the different isolates. Other enzymes, namely
      phosphatases, proteinases and phenol oxidase, were also examined, showing
      variable amounts depending on the isolate. The pH dependence of all enzymes
      tested was investigated. Endoproteinase, carboxymethyl cellulase, and
      phenoloxidase had maximum activity in the pH range of 6-8, whilst all other
      enzymes showed maximum activity at pH 4-6.

PMID- 12210549
TI  - Influence of inoculum type, inorganic salt and nitrogen to carbon ratio on
      sclerotium formation and carotenoid production in surface culture of Penicillium
      sp. PT95.
AB  - This study examined the respective effect of inoculum type, inorganic salt and
      nitrogen to carbon ratio on sclerotium formation and carotenoid production in
      surface culture of Penicillium sp. PT95. Neither the spore inoculum nor the
      mycelial pellet inoculum could result in the formation of sclerotium on a
      modified Czapek agar medium after incubation of 28 days, whereas the inoculum in
      the form of sclerotium caused the formation of numerous orange, sand-shaped
      sclerotia after incubation of 14 days. Among four inorganic salts tested,
      K(2)HPO(4) was more essential to the sclerotium formation and carotenoid
      production of strain PT95 as compared to KCl, MgSO(4) or FeSO(4). It was also
      shown that the combination of K(2)HPO(4), KCl and MgSO(4) could produce the best
      positive cooperation and give the highest sclerotia biomass (782 mg/plate) and
      carotenoid content in sclerotium (420 microg/g of dry sclerotia) as well as
      pigment yield (328 microg/plate). The medium containing 0.24 approximately 0.48
      g/l sodium nitrate-nitrogen was effective to both the sclerotium formation and
      carotenoid production of strain PT95 when available maltose-carbon concentrations
      were at 5.26 approximately 21.05 g/l. The optimal N:C ratio was found to be 1:25.

PMID- 12210550
TI  - Purification and properties of phenylalanyl aminopeptidase synthesised by
      Pseudomonas sp.
AB  - Intracellular aminopeptidase synthesized by a soil strain of Pseudomonas sp. was
      purified 323-fold using the following procedure: saturation with ammonium
      sulfate, separation by preparative electrophoresis, anion-exchange chromatography
      and gel filtration chromatography. Molecular weight of the enzyme determined
      according to the latter method was 57 kDa. Aminopeptidase showed a high substrate
      specificity and affinity to Phe-beta-naphtylamide (Phe-beta-NA) as a substrate. A
      considerable inhibition of the enzymatic activity by iodoacetamide and p
      chloromercuribenzoate (p-CMB) led to the conclusion that it was a cysteine
      aminopeptidase. Hydrosulphide compounds markedly stabilised the enzyme.
      Ethylenediaminetetra-acetic acid (EDTA), a metalloenzyme inhibitor, caused a
      double increase in the phenylalanyl aminopeptidase activity.( )Mg(2+) ions
      activated the enzyme to a negligible extent, whereas Co(2+), Cu(2+), Cd(2+) and
      Pb(2+) ions contributed to its inhibition. The highest enzymatic activity was
      observed at 37 degrees C and pH 7.0.

PMID- 12210551
TI  - The effects of NaCl and some heavy metals on the denitrification activity of
      Ochrobactrum anthropi.
AB  - Ochrobactrum anthropi is a well-known Gram-negative bacterium, with the ability
      to degrade atrazine, urea-formaldehyde and chlorophenols. Investigation were made
      of the nitrate and nitrite reduction capacities of the strain in succinate and
      glucose media, and the tolerance of its denitrification to NaCl and some heavy
      metals. Succinate proved to be a better carbon source to drive denitrification by
      O. anthropi. Batch fermentation studies in anaerobic succinate medium indicated
      reduction capacities of 85.4 +/- 9.1 and 48.6 +/- 5.2 mgh(-1)g(-1) dry cell for
      NO(3) (-) and NO(2) (-), respectively. The nitrite accumulation of the cells
      revealed that O. anthropi is a group C denitrifying bacterium. Its growth in DSM
      1 broth containing NaCl up to 40 g l(-1) demonstrates that O. anthropi belongs in
      the group of moderately halophilic bacteria. Despite the fact that 42.5 g NaCl l(
      1) caused 50% growth inhibition in DSM 1 broth, the cells in the stationary phase
      readily tolerated NaCl concentrations up to 100 g l(-1). Complete denitrification
      was achieved in test media containing 30 g NaCl l(-1) after 1 week and the
      nitrate reductase retained its activity up to 100 g NaCl l(-1). The cells were
      tolerant to Hg, Zn, Pb, Cu and Ni, and N(2) was producted at tolerated
      concentrations of the metal in the cases of Hg and Pb.

PMID- 12210552
TI  - Ubiquitin-like proteins in halobacteria.
AB  - Within our studies of protein degradation, the presence of ubiquitinylated
      proteins in haloalkaliphilic archaea was investigated. We found that
      Natronococcus occultus proteins that react with antibodies raised against
      ubiquitin appear in different growth phases, particularly in the initial and
      exponential ones. The expression of these proteins is increased when the cells
      are either treated with puromycin or starved for nutrients. Dot blot analysis of
      cell extracts with antibody against ubiquitin shows the presence of either
      ubiquitinylated or ubiquitin-like proteins not only in Natronococcus occultus,
      but also in various genera of halobacteria.

PMID- 12210553
TI  - Occurrence of crude oil degrading bacteria in gasoline and diesel station soils.
AB  - Microbial enumeration and identification were carried out on several oil
      contaminated soil samples collected from gasoline and diesel stations. Bacteria
      were the most dominant microbiota and were therefore classified to generic level.
      Eleven main genera were detected and Corynebacterium was the predominant genus in
      all the samples. Biochemical characterisation and substrate utilisation showed
      high percentage of lipolytic ability combined with high inorganic nitrogen
      utilisers. The ability of these cultures to degrade crude oil was tested
      individually and in mixed bacterial consortium at different temperatures and pH
      values. Maximum crude oil biodegradation of 78% was achieved using a bacterial
      consortium containing five cultures (Micrococcus sp. GS2-22, Corynebacterium sp.
      GS5-66, Flavobacterium sp. DS5-73, Bacillus sp. DS6-86 and Pseudomonas sp. DS10
      129) with 1% crude oil at 30 degrees C and pH 7.5. Such a consortium may be
      useful for bioaugmentation of oil contaminated environments.

PMID- 12210554
TI  - Probes for the dopamine transporter: new leads toward a cocaine-abuse therapeutic
      -A focus on analogues of benztropine and rimcazole.
AB  - In an attempt to discover a cocaine-abuse pharmacotherapeutic, extensive
      investigation has been directed toward elucidating the molecular mechanisms
      underlying the reinforcing effects of this psychostimulant drug. The results of
      these studies have been consistent with the inhibition of dopamine uptake, at the
      dopamine transporter (DAT), which results in a rapid and excessive accumulation
      of extracellular dopamine in the synapse as being the mechanism primarily
      responsible for the locomotor stimulant actions of cocaine. Nevertheless,
      investigation of the serotonin (SERT) and norepinephrine (NET) transporters, as
      well as other receptor systems, with which cocaine either directly or indirectly
      interacts, has suggested that the DAT is not solely responsible for the
      reinforcing effects of cocaine. In an attempt to further elucidate the roles of
      these systems in the reinforcing effects of cocaine, selective molecular probes,
      in the form of drug molecules, have been designed, synthesized, and
      characterized. Many of these compounds bind potently and selectively to the DAT,
      block dopamine reuptake, and are behaviorally cocaine-like in animal models of
      psychostimulant abuse. However, there have been exceptions noted in several
      classes of dopamine uptake inhibitors that demonstrate behavioral profiles that
      are distinctive from cocaine. Structure-activity relationships between chemically
      diverse dopamine uptake inhibitors have suggested that different binding
      interactions, at the molecular level on the DAT, as well as divergent actions at
      the other monoamine transporters may be related to the differing pharmacological
      actions of these compounds, in vivo. These studies suggest that novel dopamine
      uptake inhibitors, which are structurally and pharmacologically distinct from
      cocaine, may be developed as potential cocaine-abuse therapeutics.

PMID- 12210555
TI  - Chloroquine resistance in the malarial parasite, Plasmodium falciparum.
AB  - Malarial parasites remain a health problem of staggering proportions. Worldwide,
      they infect about 500 million, incapacitate tens of millions, and kill
      approximately 2.5 million (mostly children) annually. Four species infect humans,
      but most deaths are caused by one particular species, Plasmodium falciparum. The
      rising number of malarial deaths is due in part to increased drug resistance in
      P. falciparum. There are many varieties of antimalarial drug resistance, and
      there may very well be several molecular level contributions to each variety.
      This is because there are a number of different drugs with different mechanisms
      of action in use, and more than one molecular event may sometimes be relevant for
      resistance to any one class of drugs. Thus, "multidrug" resistance in a clinical
      setting likely entails complex combinations of overlapping resistance pathways,
      each specific for one class of drug, that then add together to confer the
      particular multidrug resistance phenotype. Nonetheless, rapid progress has been
      made in recent years in elucidating mechanisms of resistance to specific classes
      of antimalarial drugs. As one example, resistance to the antimalarial drug
      chloroquine, which has been the mainstay therapy for decades, is becoming well
      understood. This article focuses on recent advances in determining the molecular
      mechanism of chloroquine resistance, with particular attention to the
      biochemistry and biophysics of the P. falciparum digestive vacuole, wherein
      changes in pH have recently been found to be associated with chloroquine
      resistance.

PMID- 12210556
TI  - Anti-tumor mechanisms of valproate: a novel role for an old drug.
AB  - Valproic acid (VPA, 2-propylpentanoic acid) is an established drug in the long
      term therapy of epilepsy. During the past years, it has become evident that VPA
      is also associated with anti-cancer activity. VPA not only suppresses tumor
      growth and metastasis, but also induces tumor differentiation in vitro and in
      vivo. Several modes of action might be relevant for the biological activity of
      VPA: (1) VPA increases the DNA binding of activating protein-1 (AP-1)
      transcription factor, and the expression of genes regulated by the extracellular
      regulated kinase (ERK)-AP-1 pathway; (2) VPA downregulates protein kinase C (PKC)
      activity; (3) VPA inhibits glycogen synthase kinase-3beta (GSK-3beta), a negative
      regulator of the Wnt signaling pathway; (4) VPA activates the peroxisome
      proliferator-activated receptors PPARgamma and delta; (5) VPA blocks HDAC
      (histone deacetylase), causing hyperacetylation. The findings elucidate an
      important role of VPA for cancer therapy. VPA might also be useful as low
      toxicity agent given over long time periods for chemoprevention and/or for
      control of residual minimal disease.

PMID- 12210557
TI  - Recent advances in the discovery of flavonoids and analogs with high-affinity
      binding to P-glycoprotein responsible for cancer cell multidrug resistance.
AB  - P-glycoprotein (P-gp) is a plasma membrane glycoprotein that confers multidrug
      resistance on cells by virtue of its ability to exclude cytotoxic drugs in an ATP
      dependent manner. The most commonly considered hypothesis is that P-gp acts as an
      ATP-driven drug-export pump, the mechanism of which is not understood in detail.
      Therefore, a tremendous effort is being made to find out modulator molecules to
      inhibit P-gp. We have been developing flavonoid derivatives as a new class of
      promising modulators using a new in vitro rational-screening assay based on
      measurements of the binding-affinity toward the C-terminal nucleotide-binding
      domain (NBD2) of P-gp. This review is focused on our results obtained with a
      variety of flavonoids. Structure-activity relationships of flavonoids as
      potential MDR modulators are reported.

PMID- 12210558
TI  - Adult onset acute myelogenous leukemia and electromagnetic fields in Los Angeles
      County: bed-heating and occupational exposures.
AB  - In a large matched population-based case-control study of acute myelogenous
      leukemia (AML), we did not find incident AML in Los Angeles County (1987-1994) to
      be associated with previous exposure to electric blankets, electrically heated
      waterbeds, or occupations with presumed high exposure to electromagnetic fields.

PMID- 12210559
TI  - Developmental changes in Drosophila melanogaster following exposure to
      alternating electromagnetic fields.
AB  - This study investigated the biological effects of alternating electromagnetic
      fields (EMFs) on developmental stages of Drosophila melanogaster eggs and the
      first, second and third instar larvae stages. D. melanogaster eggs and larval
      stages were exposed to a 11 mT 50 Hz field produced by a pair of Helmholtz coils.
      Each stage was exposed to aEMFs for 2, 4, 6 and 8 h. Features of adult flies such
      as head, thorax, abdomen and other morphological changes were studied and
      compared. The frequency of abnormal flies was calculated using statistical
      methods at P <.05. The results obtained from exposing larvae in different stages
      of development showed a significant increase in the number of abnormal adult
      flies, whereas no significant increase was observed in the group arising from
      eggs exposed to aEMFs. Also, it appeared that duration of exposure correlates
      with the increase in the number of abnormal flies. There was no significant
      difference in mortality rate and sex distribution of the abnormal flies between
      field exposed and the control groups.

PMID- 12210560
TI  - Current density threshold for the stimulation of neurons in the motor cortex
      area.
AB  - The aim of this study was to determine a current density threshold for exciting
      the motor cortex area of the brain. The current density threshold for excitation
      of nerve fibres (20 microm in diameter) found in the literature is approximately
      1 A/m(2) at frequencies lower than 1 kHz. In consideration of a safety factor of
      100, the International Commission on Non-Ionizing Radiation Protection (ICNIRP)
      recommends to restrict the exposure to 0.01 A/m(2). The electromagnetic
      stimulation of neurons in the motor cortex is used in the clinical diagnosis of
      nerve lesions and neuropathy by means of magnetic or electrical transcranial
      stimulation. Combining medical data from clinical studies and technical
      specifications of the Magstim Model 200 stimulator, we were able to compute the
      current density threshold for the excitation of the human motor cortex by means
      of the finite element method (FEM). A 3D-CAD head model was built on the basis of
      magnetic resonance imaging (MRI) slices and segmented into four anatomical
      structures (scalp, skull, brain, and ventricular system) with different
      conductivities. A current density threshold for the stimulation of the motor
      cortex area of the upper limbs of 6 and 2.5 A/m(2) at 2.44 kHz and 50 Hz,
      respectively, was calculated. As these values lie above the recommended ICNIRP
      values by two orders of magnitude there is no need for lower safety standards
      with regard to stimulation of the brain.

PMID- 12210561
TI  - Determination of safety distance limits for a human near a cellular base station
      antenna, adopting the IEEE standard or ICNIRP guidelines.
AB  - This paper investigates the minimum distance for a human body in the near field
      of a cellular telephone base station antenna for which there is compliance with
      the IEEE or ICNIRP threshold values for radio frequency electromagnetic energy
      absorption in the human body. First, local maximum specific absorption rates
      (SARs), measured and averaged over volumes equivalent to 1 and to 10 g tissue
      within the trunk region of a physical, liquid filled shell phantom facing and
      irradiated by a typical GSM 900 base station antenna, were compared to
      corresponding calculated SAR values. The calculation used a homogeneous Visible
      Human body model in front of a simulated base station antenna of the same type.
      Both real and simulated base station antennas operated at 935 MHz. Antenna-body
      distances were between 1 and 65 cm. The agreement between measurements and
      calculations was excellent. This gave confidence in the subsequent calculated SAR
      values for the heterogeneous Visible Human model, for which each tissue was
      assigned the currently accepted values for permittivity and conductivity at 935
      MHz. Calculated SAR values within the trunk of the body were found to be about
      double those for the homogeneous case. When the IEEE standard and the ICNIRP
      guidelines are both to be complied with, the local SAR averaged over 1 g tissue
      was found to be the determining parameter. Emitted power values from the antenna
      that produced the maximum SAR value over 1 g specified in the IEEE standard at
      the base station are less than those needed to reach the ICNIRP threshold
      specified for the local SAR averaged over 10 g. For the GSM base station antenna
      investigated here operating at 935 MHz with 40 W emitted power, the model
      indicates that the human body should not be closer to the antenna than 18 cm for
      controlled environment exposure, or about 95 cm for uncontrolled environment
      exposure. These safe distance limits are for SARs averaged over 1 g tissue. The
      corresponding safety distance limits under the ICNIRP guidelines for SAR taken
      over 10 g tissue are 5 cm for occupational exposure and about 75 cm for general
      public exposure.

PMID- 12210562
TI  - Melanophore aggregation in strong static magnetic fields.
AB  - Contradicting results can be found in the literature on effects from magnetic
      exposure to pigment cells. We have studied the influence of strong, static,
      homogenous magnetic fields of 8 and 14 T on melanophore aggregation during
      exposure to the field. Melanophores, black pigment cells, in fish are large flat
      cells having intracellular black pigment granules. Due to large size, high
      optical contrast, and quick response to drugs, melanophores are attractive as
      biosensors as well as for model studies of intracellular processes. This is
      especially true for modeling nerve cells, since melanophores share stem cells
      with axons. Twenty experiments on black tetra fish fins were carried out in the
      two magnetic flux densities. The same number of control experiments were carried
      out in the magnet with the magnetic field turned off. Several factors, such as
      the degree of maximal aggregation, speed of aggregation, and irregularity of the
      speed, were examined. The statistical analysis showed no significant field
      effects on the aggregation, with one exception: the irregularity in aggregation
      speed in the 8 T field, compared to control. The believed reorientation of the
      cytoskeleton (microtubules) in the field or the induced Lorentz force on moving
      pigment granules, did not affect the aggregation.

PMID- 12210563
TI  - Bioelectrical parameters of the whole human body obtained through bioelectrical
      impedance analysis.
AB  - Knowledge of electrical properties of body tissues across the frequency spectrum
      is useful for tissue characterization. The bioelectric impedance analysis method,
      operating from 1 to 250 kHz (multi-frequency), was used in 23 normal male human
      subjects between the ages of 21 and 52 years, for estimation of their
      bioelectrical parameters. Amplitude of the output current was set to 800
      microA(RMS). The experimental data showed that bioelectric parameters were highly
      dependent on frequency and the presence of a threshold frequency around 4 kHz. In
      order to explain the unusual features observed in our experimental data, the
      human body was simulated through the Cole-Fricke-Cole model (RC circuit) and the
      Extended Cole-Fricke-Cole model (RLC circuit). The simulated data showed that the
      Extended Cole-Fricke-Cole model had a higher accuracy than the traditional Cole
      Fricke-Cole model. These results suggest that the unusual features could be due
      to the possible existence of inductive effects in biological cells and body
      tissues and that the inductive parameter and the threshold frequency could be
      used for characterizing the healthy tissues as well as the traditional
      bioelectric parameters.

PMID- 12210564
TI  - Effect of ultraviolet B radiation and 100 Hz electromagnetic fields on
      proliferation and DNA synthesis of Jurkat cells.
AB  - The use of ultraviolet B light (UVB) has been proven to be highly effective for
      treatment of various inflammatory skin diseases, but UVB phototherapy is limited
      by its carcinogenic side effects. It is necessary to uncover effectors that
      augment UVB so that similar or improved efficacy can be obtained with lower UVB
      doses. We found that low frequency, low intensity electromagnetic fields (EMFs)
      can act as such an effector and synergistically inhibit T lymphocyte
      proliferation. We first characterized the effects of UVB on Jurkat cells, a model
      for cutaneous T lymphocytes, and determined UVB's dose dependent inhibition of
      cell proliferation and induction of apoptosis. Cells exposed to a sublethal UVB
      dose retained their sensitivity to UVB, but repetitive irradiation seemed to
      cause accumulation of delayed DNA damage. We then exposed cells to combinations
      of UVB plus EMFs and found that 100 Hz, 1 mT EMFs decrease DNA synthesis of UVB
      activated Jurkat cells by 34 +/- 13% compared to UVB alone. The decrease is,
      however, most effective when relatively high UVB doses are employed. Since EMFs
      alone had only a very weak inhibitory effect (10 +/- 2%), the data suggest that
      EMFs augment the cell killing effects of UVB in a synergistic way. These findings
      could provide the basis for development of new and improved clinical phototherapy
      protocols.

PMID- 12210565
TI  - Contact voltage measured in residences: implications to the association between
      magnetic fields and childhood leukemia.
AB  - We measured magnetic fields and two sources of contact current in 36 homes in
      Pittsfield, MA. The first source, V(P-W), is the voltage due to current in the
      grounding wire, which extends from the service panel neutral to the water service
      line. This voltage can cause contact current to flow upon simultaneous contact
      with a metallic part of the water system, such as the faucet, and the frame of an
      appliance, which is connected to the panel neutral through the equipment
      grounding conductor. The second is V(W-E), the voltage between the water pipe and
      earth, attributable to ground currents in the water system and magnetic induction
      from nearby power lines. In homes with conductive water systems and drains, V(W
      E) can produce a voltage between the faucet and drain, which may produce contact
      current into an individual contacting the faucet while immersed in a bathtub. V(P
      W) was not strongly correlated to the magnetic field (both log transformed) (r =
      0.28; P < 0.1). On the other hand, V(W-E) was correlated to the residential
      magnetic field (both log transformed) (r = 0.54; P < 0.001), with the highest
      voltages occurring in homes near high voltage transmission lines, most likely due
      to magnetic induction on the grounding system. This correlation, combined with
      both frequent exposure opportunity for bathing children and substantial dose to
      bone marrow resulting from contact, lead us to suggest that contact current due
      to V(W-E) could explain the association between high residential magnetic fields
      and childhood leukemia.

PMID- 12210566
TI  - Effects of non-uniform static magnetic fields on the rate of myosin
      phosphorylation.
AB  - The effect on myosin phosphorylation from exposure to a magnetic field generated
      by an array of four permanent magnets was investigated. Two lateral positions in
      the non-uniform field over the array were explored, each at four vertical
      distances over the surface of the device. The rate of myosin phosphorylation was
      found to depend on the position laterally over the array as well as the distance
      from the device surface. The square magnet array was comprised of axially
      magnetized, cylindrical NdFeB permanent magnets arranged with poles of
      alternating polarity in a plane (MagnaBloc trade mark therapeutic device).
      Detailed dosimetry of the magnet array was compiled: the magnetic flux density
      averaged over the exposure volume spanned the range 0.7-86 mT for the eight
      different exposure positions. The corresponding range for the absolute field
      gradient was 0.4-20 T/m. Comparing the dosimetry to the experimental outcome, our
      results imply that magnetic field amplitude alone is not sufficient to describe
      the influence of the field in this preparation.

PMID- 12210567
TI  - Magnetic anisotropy of the radula of chiton Acanthochiton rubrolinestus LISCHKE.
AB  - The magnetic anisotropy of the whole radula, the major lateral radula teeth, and
      magnetic material in the major lateral radula teeth of the chiton Acanthochiton
      rubrolinestus LISCHKE have been studied by a magnetic torque meter and
      superconducting quantum interference device (SQUID) magnetometer. The length and
      width axes of the teeth are the easily magnetized axes, while the thickness axis
      is difficult to magnetize. The width and thickness axes of the radula are the
      easily magnetized axes, and the length axis is difficult to magnetize. The
      measurement results of the whole radula and the major lateral radula teeth agree
      well with each other. The magnetic anisotropy of the magnetic material is given
      as well as a possible distribution of the magnetic material in the major lateral
      radula teeth.

PMID- 12210569
TI  - Prenatal detection of structural abnormalities of chromosome 18: associations
      with interphase fluorescence in situ hybridization (FISH) and maternal serum
      screening.
AB  - We describe two cases of prenatally ascertained isochromosome 18. Case 1 included
      both an isochromosome 18p and an isochromosome 18q, while Case 2 involved only an
      isochromosome 18q. Both of these cases were associated with a positive maternal
      serum triple screen trisomy 18 risk (greater than 1 in 100 risk). In addition,
      fluorescence in situ hybridization (FISH) was performed on uncultured amniotic
      fluid interphase cells in both cases looking for aneuploidy for chromosomes 13,
      18, 21, X and Y. The results of the interphase analyses support the common
      knowledge that careful interpretation of interphase FISH analysis is necessary
      and that results should be followed by full cytogenetic analysis. To our
      knowledge these are the first reported cases of structurally abnormal chromosomes
      18 being associated with a positive maternal serum triple screen for trisomy 18.

PMID- 12210570
TI  - Uniparental disomy in fetuses diagnosed with balanced Robertsonian
      translocations: risk estimate.
AB  - Forty-two fetuses with non-homologous Robertsonian translocations were analyzed
      for uniparental disomy (UPD). One fetus with a de novo translocation t(13q;14q)
      had maternal isodisomy of chromosome 14. In a summary of the published data
      (including the present study), 315 cases were analyzed for UPD after prenatal
      diagnosis of balanced Robertsonian translocations, of these two fetuses had UPD,
      giving a risk estimate of 0.65% (CI 0.2-2.3). This risk justifies the
      recommendation of UPD analysis in fetuses diagnosed prenatally with Robertsonian
      translocations, with the emphasis on the chromosomes known to contain imprinted
      genes, such as 14 and 15. We also discuss the possibility of UPD in offspring of
      Robertsonian translocation carriers with normal karyotype. Based on the risk for
      UPD in fetuses with Robertsonian translocation we suggest to test these fetuses
      for UPD and to do so on amniocytes rather than chorionic villi when the risk for
      unbalanced karyotype is approximately 1%, comparable to the risk for UPD.

PMID- 12210571
TI  - Female pseudohermaphroditism in a fetus with a deletion 9(q22.2q31.1).
AB  - Interstitial deletions of chromosomal region 9q are rarely seen. We report the
      first prenatal diagnosis of a de novo interstitial deletion 9q. The fetus was
      karyotyped for intrauterine growth retardation (IUGR). Conventional and molecular
      cytogenetics showed female karyotype with a de novo deletion of the chromosomal
      region 9(q22.2q31.1) leading to a partial monosomy 9q. At autopsy, the fetus
      showed growth retardation, dysmorphy, and a female pseudohermaphroditism. These
      results suggest that a gene(s) for genital development reside in chromosomal
      region 9q22.2q31.1.

PMID- 12210572
TI  - Maternal serum hyperglycosylated human chorionic gonadotrophin (HhCG) in the
      first trimester of pregnancies affected by Down syndrome, using a sialic acid
      specific lectin immunoassay.
AB  - In a series of 54 cases of pregnancies complicated by Down syndrome and 224
      unaffected pregnancies we examined maternal serum levels of hyperglycosylated
      human chorionic gonadotrophin (HhCG) in samples collected in the first trimester
      (11-13 weeks) using a sialic acid-specific lectin immunoassay. We compared these
      levels with those of other potential first trimester serum markers [free beta
      hCG, pregnancy-associated plasma protein A (PAPP-A) and total hCG (ThCG)] and
      modeled detection rates and false-positive rates of various biochemical markers
      in conjunction with fetal nuchal translucency (NT) and maternal age using an
      maternal age standardized population. Maternal serum HhCG in cases of Down
      syndrome were significantly elevated (median MoM 1.97) with 24/54 (44%) of cases
      above the 95th centile for unaffected pregnancies. Free beta-hCG was also
      elevated (median MoM 2.09) with 33% of cases above the 95th centile. PAPP-A
      levels were reduced (median MoM 0.47) with 38% below the 5th centile. ThCG
      levels, whilst elevated (median MoM 1.34), had only 20% of cases above the 95th
      centile. Maternal serum HhCG levels were not correlated with fetal NT but showed
      significant correlation with ThCG and free beta-hCG and with PAPP-A in the Down
      syndrome group (r=0.536). Maternal serum HhCG levels in cases with Down syndrome
      had a significant correlation with gestational age, increasing as the gestation
      increased. When HhCG was combined together with fetal NT, PAPP-A and maternal
      age, at a 5% false-positive rate the modeled detection rate was 83%, some 6%
      lower than when free beta-hCG was used and some 4% better than when ThCG was
      used. Maternal serum HhCG is unlikely to be of additional value when screening
      for Down syndrome in the first trimester.

PMID- 12210573
TI  - Chondrodysplasia punctata (CDP) with features of the tibia-metacarpal type and
      maternal phenytoin treatment during pregnancy.
AB  - We describe a 2-year-old boy with chondrodysplasia punctata (CDP). The boy was
      exposed to phenytoin, in combination with carbamazepine, during pregnancy. There
      has been previous evidence for a connection between phenytoin exposure during
      pregnancy and chondrodysplasia punctata. The boy had clinical and some
      radiological characteristic features of CDP, of the tibia-metacarpal type. We
      know of no other report on a child exposed to phenytoin during pregnancy who
      developed CDP of this type.

PMID- 12210574
TI  - Prenatal identification of esophageal atresia: the role of ultrasonography for
      evaluation of functional anatomy.
AB  - OBJECTIVE: To suggest a new ultrasonographic approach for prenatal diagnosis of
      esophageal atresia (EA). METHODS: Since 1995, whenever EA is suspected, we
      perform a systematic multiplanar ultrasonographic scanning of the fetal upper
      body in order to demonstrate an esophageal pouch. This includes three image plans
      of the neck and upper chest: coronal, sagittal and axial views in the cephalic
      direction. The scan time is 20-30 min. RESULTS: Twenty-five pregnant patients
      were referred during the period under study for prenatal examinations due to
      polyhydramnios and/or absent or small stomach. In six fetuses an esophageal pouch
      was demonstrated at ultrasonography in utero, thus a definitive diagnosis of EA
      was obtained. All six were confirmed with EA postpartum. In 19 fetuses an
      esophageal pouch was not demonstrated and all delivered normal neonates. During
      the same period two additional newborns, who were not included in the referred
      patients because amniotic fluid volume and stomach size were normal, were
      diagnosed postpartum with EA. The earliest gestational age of pouch visualization
      was at 23 weeks. The sagittal view was the best for visualizing a low-level
      pouch, and the coronal view was optimal for revealing a high pouch. CONCLUSIONS:
      Our three-sectional view of the neck and upper chest is useful for in utero
      detection of esophageal pouch that may enhance the prenatal diagnosis of EA. The
      positive predictive value for prenatal ultrasound for detecting EA is 100% with a
      sensitivity of 80%.

PMID- 12210575
TI  - Prenatal diagnosis of a 45,X male with a SRY-bearing chromosome 21.
AB  - Male phenotype associated with a 45,X karyotype is an infrequent finding. We
      present a case diagnosed prenatally on amniocentesis performed for maternal age.
      The male phenotype was associated with a translocation of a distal part of Yp
      including the pseudoautosomal SHOX gene and SRY gene on the short arm of a
      chromosome 21. By DNA analysis we could show that the X chromosome was of
      maternal origin and that the breakpoint was in interval 3 of the Y chromosome.
      Mechanisms and genetic counselling are discussed based on a review of published
      cases of 45,X and XX males.

PMID- 12210576
TI  - Isochromosome 5p mosaicism at prenatal diagnosis: observations and outcomes in
      six cases at chorionic villus sampling and one at amniocentesis.
AB  - We present six cases of 47,+i(5p)/46 mosaicism diagnosed at chorionic villus
      sampling (CVS), this being the first prospective series to be reported. The
      clinical indication in each was advanced maternal age. Further prenatal studies
      in four (amniocentesis, plus fetal blood sampling in one) did not show the
      isochromosome. In one case, subsequent amniocentesis showed 1/48 in situ colonies
      with the isochromosome, but fetal blood was karyotypically normal. These five
      pregnancies resulted in phenotypically normal livebirths; further normal follow
      up reports (from age 4 months through 4 years) are noted in four of these.
      Analysis of placental tissue in one case confirmed the presence of the i(5p)
      mosaicism. In the remaining case, in which 100% of CVS cultured cells had the
      i(5p), the pregnancy was terminated. Fetal skin fibroblasts did not show the
      i(5p). Thus, in none of these six cases was true fetal mosaicism detected, nor an
      abnormal phenotype noted. We suggest that a 47,+i(5p)/46 karyotype, detected at
      CVS, may frequently reflect confined placental mosaicism. In addition, we report
      a case of the primary diagnosis of 47,+i(5p)/46 mosaicism at amniocentesis. The
      infant appeared normal at birth, but a brain malformation was subsequently
      identified.

PMID- 12210578
TI  - Prenatal diagnosis and intrafamilial clinical heterogeneity of Fraser syndrome.
AB  - Fraser syndrome (MIM 219000) is a rare disorder of autosomal recessive
      inheritance, characterized by the association of cryptophthalmos, syndactyly and
      genital abnormalities. Here we report on two cases of Fraser syndrome
      (cryptophthalmos syndrome) in a non-consanguineous couple, with variable
      expression in echographic, clinical and autopsy findings. Furthermore, we
      highlight the difficulties in prenatal diagnosis of Fraser syndrome.

PMID- 12210577
TI  - Rapid prenatal diagnosis of sickle cell diseases using oligonucleotide ligation
      assay coupled with laser-induced capillary fluorescence detection.
AB  - Prenatal diagnosis of sickle cell diseases has been available for several years,
      and our laboratory has performed over 1000 prenatal diagnoses. However, currently
      available techniques are labor-intensive and time-consuming, and thus the
      diagnosis is delayed, making the mother's decision difficult. We describe a
      rapid, high-throughput technique based on the ligation assay coupled with
      automated capillary fluorescence detection. This new approach allows the
      diagnosis of both Hgb S and Hgb C to be available in a few hours. We have
      utilized this technique in 30 prenatal diagnoses and found it to be in complete
      agreement with the standard diagnoses.

PMID- 12210579
TI  - Prenatal diagnosis of female monozygotic twins discordant for Turner syndrome:
      implications for prenatal genetic counselling.
AB  - We describe a set of monozygotic (MZ) female twins, one of whom presented with a
      typical Turner syndrome (TS) phenotype and the other a normal female phenotype.
      Prenatal fetal ultrasonographic examination showed a monochorial diamniotic
      pregnancy with a hygroma colli and growth delay in Twin A and no anomalies in
      Twin B. Karyotypic analysis performed on fetal blood samples demonstrated a
      46,XX/45,X (23/2) mosaicism in Twin A and a normal 46,XX chromosome constitution
      in Twin B. At birth, Twin A presented with a typical TS and Twin B had a normal
      female phenotype. Postnatal cytogenetic investigation of blood lymphocytes showed
      the same 46,XX/45,X mosaicism in both twins: 46,XX/45,X (40/7) in Twin A and
      46,XX/45,X (40/5) in Twin B. Further investigations at the age of 10 months
      showed in Twin A a 46,XX/45,X (98/2) mosaicism in lymphocytes and 100% of 45,X
      (50 analysed cells) in fibroblasts, and in Twin B a normal 46,XX (100 analysed
      cells) chromosome constitution in lymphocytes but a mild 46,XX/45,X (78/2)
      mosaicism in fibroblasts. Monozygosity was confirmed by molecular analysis. To
      our knowledge, this is the first report of prenatal diagnosis of MZ female twins
      discordant for TS. Review of reported sets of MZ female twins (eight cases) or
      triplets (one case) discordant for TS shows, as in the present case, that the
      phenotype correlates better with the chromosomal distribution of mosaicism in
      fibroblasts than in lymphocytes. In the blood of MZ twins chimerism may modify
      the initial allocation of the mosaicism. These results suggest that, in cases of
      prenatal diagnosis of MZ female twins discordant for TS, the phenotype of each
      twin would be better predicted from karyotype analysis of cells from amniotic
      fluid than from fetal blood.

PMID- 12210580
TI  - Prenatal prediction of childhood-onset spinal muscular atrophy (SMA) in Turkish
      families.
AB  - Childhood-onset spinal muscular atrophy (SMA) is one of the most common
      neurodegenerative genetic disorders. SMN1 is the SMA-determining gene deleted or
      mutated in the majority of SMA cases. There is no effective cure or treatment for
      this disease yet. Thus, the availability of prenatal testing is important. Here
      we report prenatal prediction for 68 fetuses in 63 Turkish SMA families using
      direct deletion analysis of the SMN1 gene by restriction digestion. The genotype
      of the index case was known in 40 families (Group A) but unknown in the remaining
      23 families (Group B). A total of ten fetuses were predicted to be affected.
      Eight of these fetuses were derived from Group A and two of these fetuses were
      from Group B families. Two fetuses from the same family in Group A had the
      SMNhyb1 gene in addition to homozygous deletion of the NAIP gene. One fetus from
      Group A was homozygously deleted for only exon 8 of the SMN2 gene, and further
      analysis showed the presence of both the SMN1 and SMNhyb1 genes but not the SMN2
      gene. In addition, one carrier with a homozygous deletion of only exon 8 of the
      SMN1 gene was detected to have a SMNhyb2 gene, which was also found in the fetus.
      To our knowledge, these are the first prenatal cases with SMNhyb genes. Follow-up
      studies demonstrated that the prenatal predictions and the phenotype of the
      fetuses correlated well in 33 type I pregnancies demonstrating that a careful
      molecular analysis of the SMN genes is very useful in predicting the phenotype of
      the fetus in families at risk for SMA.

PMID- 12210581
TI  - Hypomandibular faciocranial dysostosis in consanguineous parents revealed by
      ultrasound prenatal diagnosis.
AB  - We report here the fourth case of hypomandibular faciocranial dysostosis (HFD).
      The diagnosis was made at birth on the association of severe retrognathia,
      microstomia, severe hypoglossia with glossoptosis, persistent buccopharyngeal
      membrane, median cleft palate, bifid uvula, down-slanting palpebral fissures,
      short nose with anteverted nares, laryngeal hypoplasia, and low-set ears. A
      severe microstomia and micrognathia were detected by ultrasound at 31 weeks of
      gestation. Interestingly, even though the present case exhibits many facial
      dysmorphic features characteristic of HFD, craniosynostosis was absent. This
      report suggests that craniosynostosis is not mandatory for the diagnosis of this
      condition. Furthermore, we present a new argument for an autosomal recessive mode
      of inheritance for HFD.

PMID- 12210582
TI  - Is unexplained third trimester intrauterine death of fetuses with gastroschisis
      caused by umbilical cord compression due to acute extra-abdominal bowel
      dilatation?
AB  - We report on a case of gastroschisis in which sudden dilatation of extra
      abdominal bowel at 34+1 weeks was followed by an unusual umbilical flow velocity
      waveform (diastolic notching). The condition was associated with normal umbilical
      Doppler indices, brain sparing effect and a non-reactive cardiotocograph (CTG).
      Findings at postnatal surgery strongly suggested severe cord compression by the
      herniated dilated bowel. The significance of notching in the umbilical artery
      waveform is discussed, as is the potential importance of this sign in the
      prepartum management of fetuses with gastroschisis.

PMID- 12210583
TI  - First trimester screening with free beta-hCG, PAPP-A and nuchal translucency in
      pregnancies conceived with assisted reproduction.
AB  - OBJECTIVE: To evaluate the effect of in vitro fertilization (IVF) and
      intracytoplasmic sperm injection (ICSI) on free beta-human chorionic
      gonadotrophin (beta-hCG), pregnancy-associated plasma protein A (PAPP-A) and
      nuchal translucency (NT). METHODS: First trimester maternal dried whole blood
      specimens from 74 singleton pregnancies (32 by IVF and 42 by ICSI) and 30 twin
      pregnancies (16 by IVF and 14 by ICSI) in which conception was achieved with
      assisted reproduction techniques were matched with five controls resulting in 370
      singleton controls and 150 twin controls. NT was measured using the Fetal
      Medicine Foundation protocol. Free beta-hCG, PAPP-A and NT levels were compared
      between the IVF and control groups and between the ICSI and control groups using
      the Mann-Whitney U test. RESULTS: In singleton pregnancies, the only significant
      difference was a 21% (95% CI: -35%--7%) reduction in PAPP-A in IVF cases. In twin
      pregnancies, the only significant difference was a 12% (95% CI: -34%--3%)
      reduction in NT in IVF cases. In singleton pregnancies, the false-positive rate
      for Down syndrome screening was 1.4% and 1.9% greater for the IVF and ICSI
      groups, respectively, compared to controls for a general screening population.
      CONCLUSIONS: Patients undergoing assisted reproduction techniques should be
      counseled about the possibility of increased false-positive rates. Larger studies
      are needed to confirm this observation and to develop appropriate adjustment
      factors to reduce false-positive rates.

PMID- 12210584
TI  - Outcome of prenatally diagnosed trisomy 6 mosaicism.
AB  - We report the prenatal diagnosis of trisomy 6 mosaicism via amniocentesis, in
      which trisomy 6 cells were identified in three of five culture vessels with 33%
      (5/15) of colonies showing trisomic cells. The pregnancy was electively
      terminated and examination revealed minor abnormalities (shortening of the
      femurs, micrognathia, posterior malrotation of the ears, and bilateral
      camptomelia of the second digit of the hands and fifth digits of the feet).
      Cytogenetic analysis of the placenta showed trisomy 6 in 100% of 20 cells
      studied. Karyotype was 46,XX in 100 cells examined from fetal skin. There are
      relatively few prenatally diagnosed cases of mosaic trisomy 6 at amniocentesis.
      Confined placental mosaicism (CPM) has been postulated in other cases where
      follow-up cytogenetic studies were not available. The present case differs from
      those previously reported, as it appears to represent CPM of chromosome 6 with
      phenotypic effects to the fetus.

PMID- 12210585
TI  - Novel mutation and prenatal sonographic findings of glutaric aciduria (type I) in
      two Taiwanese families.
AB  - Glutaric aciduria type I (GA I) is an autosomal recessively inherited inborn
      error with a defect of the enzyme glutaryl-CoA dehydrogenase (GCDH), which has
      never been diagnosed prenatally in Taiwanese patients. We present the prenatal
      sonographic findings and mutational analysis data of three children in two
      Taiwanese families. One patient from each family was diagnosed postnatally due to
      macrocephaly and neurological deterioration at 4 months and 10 months,
      respectively. The third child, sister of the first patient, was diagnosed
      prenatally at 11 weeks' gestation through chorionic villus sampling (CVS).
      Molecular analysis revealed that the fetus and child in Family 1 were homozygous
      for a common mutation, IVS10 -2A>C, which has not been reported in the Caucasian
      population. The patient in Family 2 was a compound heterozygote for IVS10 -2A>C
      and a novel mutation 749T>C (L238P). After genetic counseling, the couple decided
      to continue the second pregnancy. However, dilatation of quadrigeminal cistern
      (QC) and suspicious macrocephaly were noted at 30 weeks. Progressive dilatation
      of the QC associated with macrocephaly, fronto-temporal atrophy and wide space of
      perisylvian fissure were found in the follow-up scans. The affected girl was
      delivered at 37 weeks' gestation by cesarean section. Postnatal magnetic
      resonance imaging (MRI) studies confirmed the prenatal sonographic findings. With
      prenatal sonographic findings and mutational analysis presented in the present
      cases, the feasibility of prenatal diagnosis of GA I in high-risk pregnancy can
      not be overlooked.

PMID- 12210587
TI  - Second trimester molecular diagnosis of a stop codon FGFR3 mutation in a type I
      thanatophoric dysplasia fetus following abnormal ultrasound findings.

PMID- 12210586
TI  - Comparison and integration of first trimester fetal nuchal translucency and
      second trimester maternal serum screening for fetal Down syndrome.
AB  - BACKGROUND: It is uncertain whether first trimester nuchal translucency (NT) is
      more effective than the well-established second trimester serum screening for
      fetal Down syndrome or whether their combination works best. We report data from
      a large multicentre non-interventional trial in which all subjects underwent both
      first and second trimester screening. METHODS: All women who attended the
      obstetric clinic before 15 weeks' gestation were recruited. An ultrasound
      examination was performed at 10 to 14 weeks to measure the NT. The nuchal
      measurements were not acted upon unless the fetus showed gross features of
      hydrops fetalis. All women had serum alpha-fetoprotein (AFP) and human chorionic
      gonadotrophin (hCG) assay at 15 to 20 weeks. The Down syndrome risk assigned by
      serum screening was disclosed and amniocentesis was offered if this assigned risk
      was >or=1:250 or if the women were 35 years and older. The efficacy of different
      combinations of screening markers was compared. RESULTS: Between January 1997 and
      August 2000, 17 590 women were recruited (19% >or=35 years old). After excluding
      subjects who miscarried, defaulted the serum test and other reasons, 16 237
      pregnancies were analysed. Of these, 35 pregnancies were affected by Down
      syndrome (2.2 cases per 1000 pregnancies). At a false-positive rate of 5%, the
      detection rate of Down syndrome by NT alone, NT and age, serum hCG, AFP and age,
      and NT, hCG, AFP and age were 61%, 69%, 73% and 86%, respectively. CONCLUSION:
      Integration of NT and second trimester serum AFP and hCG assay yielded the best
      screening efficacy for Down syndrome.

PMID- 12210588
TI  - Maternal cell contamination in an amniotic fluid sample.

PMID- 12210589
TI  - Improved methodology for evaluating nuchal thickness in the second trimester.

PMID- 12210590
TI  - Morphological analysis of cementum and root dentin after Er:YAG laser
      irradiation.
AB  - BACKGROUND AND OBJECTIVES: To investigate the morphology of cementum and root
      dentin after Er:YAG laser irradiation with and without water coolant, compared to
      that after CO(2) laser irradiation and an untreated surface. STUDY
      DESIGN/MATERIALS AND METHODS: Ten extracted healthy human teeth were used. Er:YAG
      and CO(2) lasers were applied with energy outputs of 0.4 W, with and without
      coolant and 0.5 W, without coolant, respectively. Scanning electron microscopy
      (SEM) analysis was performed at high and ultra-high magnifications. RESULTS: The
      surface of cementum was micro-irregular with numerous projections while that of
      dentin appeared scaly after Er:YAG laser irradiation. Unlike after CO(2) laser
      treatment, no major melting or cracking was observed with Er:YAG laser treatment.
      The use of water spray produced fine micro-irregularities without attached
      debris. Ultra-high magnification revealed similar microparticles-composed aspects
      for both cementum and dentin. However, the more porous structure of the surface
      was observed after Er:YAG laser irradiation without water spray. CONCLUSIONS:
      Cementum and root dentin presented distinct micro-roughness after Er:YAG laser
      irradiation, possibly due to structural differences in the original tissue.
      However, under ultra-high magnifications, both cementum and dentin presented
      similar characteristics of the irradiated surface. In addition, the use of water
      spray during laser irradiation minimized thermal effects and resulted in a
      cleaner and less porous surface.

PMID- 12210591
TI  - Oral bacteria in multi-species biofilms can be killed by red light in the
      presence of toluidine blue.
AB  - BACKGROUND AND OBJECTIVES: Oral bacteria can be killed by light in the presence
      of a suitable photosensitizer, and this could be used in the treatment of oral
      infections. In these diseases, however, bacteria are present as biofilms, which
      are refractive to antimicrobial agents. The purpose of this study was to
      determine whether oral bacterial biofilms were susceptible to lethal
      photosensitization. STUDY DESIGN/MATERIALS AND METHODS: Multi-species biofilms of
      oral bacteria were irradiated with light from a helium/neon laser in the presence
      of toluidine blue O (TBO) and the survivors enumerated. Controls examining the
      effects of light and TBO alone were also included. The biofilms were also
      examined by confocal scanning laser microscopy (CSLM). RESULTS: CSLM revealed
      that the biofilms had structures similar to those of dental plaque. Although, the
      biofilms consisted of extremely large numbers of bacteria ( approximately 9 x
      10(9)), 97.4% were killed following irradiation with 31.5 J of laser light in the
      presence of 25 microg/ml TBO. CONCLUSIONS: Substantial numbers of oral bacteria
      in multi-species biofilms can be killed by light in the presence of TBO. This may
      be useful in the treatment of dental plaque-related diseases.

PMID- 12210592
TI  - Therapeutic low energy laser improves the mechanical strength of repairing medial
      collateral ligament.
AB  - BACKGROUND AND OBJECTIVES: Low energy laser therapy has been shown to enhance
      collagen production but its effect on tissue strength is not well reported. We
      tested the effects of therapeutic laser on the strength of healing medial
      collateral ligaments (MCLs) in rats. STUDY DESIGN/MATERIALS AND METHODS: Twenty
      four rats received surgical transection to their right MCL and eight received
      sham operation. After surgery, 16 received a single dose of gallium aluminum
      arsenide laser to their transected MCL for 7.5 minutes (n = 8) or 15 minutes (n =
      8) and eight served as control with placebo laser, while the sham group didn't
      receive any treatment. The MCLs were biomechanically tested at either 3 or 6
      weeks post-operation. RESULTS: The normalized ultimate tensile strength (UTS) and
      stiffness of laser and sham groups were larger than control (P < 0.001). The UTS
      of laser and sham groups were comparable. Laser and sham groups had improved in
      stiffness from 3 to 6 weeks (P < 0.001). CONCLUSIONS: A single dose of low energy
      laser therapy improves the UTS and stiffness of repairing MCL at 3 and 6 weeks
      after injury.

PMID- 12210593
TI  - Importance of cutaneous cooling during photothermal epilation: theoretical and
      practical considerations.
AB  - BACKGROUND AND OBJECTIVES: Sapphire contact cooling is widely used to prevent non
      specific epidermal injury from occurring during selective laser treatment of
      unwanted hair and vascular lesions. This small study was performed to examine the
      clinical response of the skin to 800-nm laser irradiation with varying extent of
      cutaneous sapphire contact cooling. Observed clinical responses are compared to
      those predicted by theoretical analysis in an attempt to construct a more
      complete picture of sapphire contact cooling and its role in preventing non
      targeted tissue devitalization during laser treatment of the skin using a
      wavelength, pulse duration, and radiant exposure commonly used for laser hair
      removal. STUDY DESIGN/MATERIALS AND METHODS: Three subjects each received a total
      of three pulses of laser light (800 nm) of equal radiant exposure (60 J/cm(2)),
      pulse duration (30 msec), and spot size (9 mm x 9 mm), but with varying extent of
      cutaneous cooling. One site was pre-cooled and heat-sinked with a chilled (5
      degrees C) sapphire window in contact with the skin; another site was heat-sinked
      only with a room-temperature (20 degrees C) sapphire window in contact with the
      skin; and a third site received no pre-cooling or heat-sinking. Each site was
      examined immediately after treatment and at intervals throughout a 3-month
      period. The thermal response of the tissue was calculated in each case using a
      Monte Carlo model for light transport in multi-layered tissues coupled with an
      axisymmetric finite-difference heat diffusion model. Thermal injury was modeled
      as a first-order kinetic rate process using an Arrhenius expression. RESULTS: In
      all three subjects, the sites that were pre-cooled and heat-sinked showed no
      evidence of epidermal or dermal devitalization. The three sites that were heat
      sinked only had a few patches of perifollicular epidermal devitalization and
      subsequent desquamation without any permanent epidermal or dermal injury, as
      would be evidenced by pigmentary alteration or textural change. In each subject,
      the site that received no pre-cooling or heat-sinking sustained epidermal and
      dermal devitalization, appearing as ulceration and resulting in sustained
      erythema and textural alteration. Clinical responses predicted by theoretical
      analysis agree with the clinical observations and show that the dominant effect
      of sapphire contact cooling for pulse durations of 30 msec or less is the
      reduction of fluence within the epidermis resulting from index matching at the
      skin surface. CONCLUSIONS: The results of this small study suggest that by
      judiciously selecting the laser pulse duration and pre-cooling and heat-sinking
      the epidermis in a manner that provides index matching and compression of the
      skin, epidermal damage can be avoided while administering the highest, most
      effective radiant exposures.

PMID- 12210594
TI  - Acne treatment with a 1,450 nm wavelength laser and cryogen spray cooling.
AB  - BACKGROUND AND OBJECTIVES: A laser with a wavelength in the mid-IR range
      targeting the depth in skin where sebaceous glands are located in combination
      with cryogen spray cooling was evaluated for treatment of acne. In this non
      ablative treatment, the laser energy heats the dermal volume encompassing
      sebaceous glands whereas the cold cryogen spray preserves the epidermis from
      thermal damage. STUDY DESIGN/MATERIALS AND METHODS: Monte Carlo simulations and
      heat transfer calculations were performed to optimize the heating and cooling
      parameters. A variety of heating and cooling parameters were tested in an in vivo
      rabbit ear study to evaluate the histological effect of the device on sebaceous
      glands and skin. Similar experiments were performed on ex vivo human skin. A
      clinical study for the treatment of acne on backs of human males was also
      conducted. RESULTS: Monte Carlo simulations and heat transfer calculations
      resulted in a thermal damage profile that showed epidermal preservation and peak
      damage in the upper dermis where sebaceous glands are located. Ex vivo human skin
      histology confirmed the damage profile qualitatively. In vivo rabbit ear
      histology studies indicated short-term thermal alteration of sebaceous glands
      with epidermal preservation. In the human clinical study on the back, a
      statistically significant reduction in lesion count on the treated side compared
      to the control side was seen (p < 0.001). Side effects were transient and few.
      CONCLUSIONS: The studies reported here demonstrate the feasibility of treating
      acne using a photothermal approach with a mid-IR laser and cryogen cooling.

PMID- 12210595
TI  - Selective photothermolysis of the sebaceous glands for acne treatment.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study is to evaluate the efficacy
      of a long pulse diode laser (Cynosure, Inc.) to target and destroy enlarged
      sebaceous glands that are preloaded with Indocyanine green (ICG) chromophore.
      STUDY DESIGN/MATERIALS AND METHODS: This study was designed in three phases.
      First, preliminary studies were performed to determine the ability of ICG to
      penetrate into enlarged sebaceous glands. Once penetration of the sebaceous gland
      was confirmed, the second phase was to determine the necessary parameters for the
      diode laser to effectively target the ICG loaded glands. This was done using
      laser-tissue interaction analysis. The final phase was done with patients that
      had active acne on their back to determine if selective destruction of the
      sebaceous glands could be achieved and also to assess the safety and efficacy of
      this novel treatment for acne. RESULTS: Fluorescence microscopy of biopsy samples
      show evidence of ICG penetration into the sebaceous glands. Histological
      examination of biopsy samples from the treated areas finds selective necrosis of
      the sebaceous glands. Preliminary clinical results demonstrate a decrease in acne
      noted in the treatment area at 3, 6, and 10 months follow-up. CONCLUSIONS: ICG
      and diode laser treatment is a new approach for the treatment of acne based on
      experimentally observed selective photothermolysis of the sebaceous glands.

PMID- 12210596
TI  - Magnetite tattoos.
AB  - BACKGROUND AND OBJECTIVES: Tattoo removal is a significant problem. The
      extraction of magnetite (Fe(3)O(4)) ink tattoos by a magnetic field was
      investigated, with and without Q-switched laser treatment. STUDY DESIGN/MATERIALS
      AND METHODS: Magnetite particles (1.4 microm) were used to make mature, black
      skin tattoos on hairless albino rats. A Q-switched ruby laser (QSRL) 3.5 J/cm(2),
      6.5-mm spot size, 40-nanosecond pulse width was used for treatment. Permanent
      magnets (1.4 T, 6-mm diameter) were tested to extract the magnetite particles,
      alone and after QSRL. Lightening of treated tattoos was measured from digital
      photographs, and the amount and distribution of magnetite in skin biopsies was
      scored blindly. RESULTS: External application of magnets on mature magnetite
      tattoos without prior QSRL treatment, did not significantly extract, lighten,
      darken, or change their histologic appearance. A magnetic field applied
      immediately after QSRL treatment extracted some ink when epidermal injury was
      present, and caused significant redistribution of magnetite into the upper dermis
      with vertical banding along magnetic field lines. When applied for 3 weeks
      following QSRL, magnets caused darkening of tattoos. CONCLUSIONS: Magnetite skin
      tattoos can be manipulated by external magnets, especially after Q-switched laser
      treatment. Magnetically-extractable tattoos may be feasible.

PMID- 12210597
TI  - Holmium: YAG laser-induced liquid jet knife: possible novel method for
      dissection.
AB  - BACKGROUND AND OBJECTIVES: Making surgical incisions in vessel-rich organs
      without causing bleeding is difficult. Thus, it is necessary to develop new
      devices for this purpose, especially for surgery involving small vessels as in
      neurosurgery, where damage against even small cerebral vessels result in severe
      neurological deficits. STUDY DESIGN/MATERIALS AND METHODS: A laser-induced liquid
      jet was generated by irradiating pulsed Holmium Yttrium-Aluminum-Garnet (Ho: YAG)
      laser (beams of 350 microseconds pulse width) within a copper tube (internal
      diameter, 1 mm) with pure water (150 ml /hour). Ho: YAG laser beams were
      irradiated through an optical fiber (core diameter, 0.4 mm). The influence of the
      input of laser energy, structure of the nozzle, and the stand-off distance
      between the optical fiber tip and nozzle exit on the jet velocity was measured by
      a high-speed video camera to evaluate controllability of jet. The effect on
      artificial organs made of 10 and 30%(w/v) gelatin, each of which represent
      features of soft tissue and blood vessels. RESULTS: Jet velocity increased in
      proportion to gain in laser energy input, and maximum penetration depth into
      10%(w/v) gelatin was 35 mm by single exposure at 350 mJ/pulse without impairing a
      vessel model. Shapes of nozzle also modified jet velocity with optimal
      nozzle/tube area ratio of 0.25. CONCLUSIONS: The laser-induced liquid jet has
      excellent potential as a new tool for removing soft tissue without damaging vital
      structures.

PMID- 12210598
TI  - Myocardium tissue ablation with high-peak-power nanosecond 1,064- and 532-nm
      pulsed lasers: influence of laser-induced plasma.
AB  - BACKGROUND AND OBJECTIVES: We investigated the mechanism and characteristics of
      porcine myocardium tissue ablation in vitro with nanosecond 1,064- and 532-nm
      pulsed lasers at laser intensities up to approximately 5.0 GW/cm(2). Particular
      attention was paid to study the influence of the laser-induced plasma on the
      ablation characteristics. The applicability of these two lasers to
      transmyocardial laser revascularization (TMLR) was discussed. STUDY
      DESIGN/MATERIALS AND METHODS: Porcine myocardium tissue samples were irradiated
      with 1,064- and 532-nm, Q-switched Nd:YAG laser pulses, and the ablation depths
      were measured. The temporal profiles of the laser-induced optical emissions were
      measured with a biplanar phototube. For the ablated tissue samples, histological
      analysis was performed with an optical microscope and a polarization microscope.
      RESULTS: The ablation efficiency at 1,064 nm was higher than that at 532 nm. The
      ablation threshold at 1,064 nm (approximately 0.8 GW/cm(2)) was lower than that
      at 532 nm (approximately 1.6 GW/cm(2)), in spite of the lower absorption
      coefficient being expected at 1,064 nm. For the 1,064-nm laser-ablated tissues,
      thermal damage was very limited, while damage presumably caused by the mechanical
      effect was observed in most of the cases. For the 1,064-nm laser ablation, the
      ablation threshold was equal to the threshold of the laser-induced optical
      emission (approximately 0.8 GW/cm(2)), while for the 532-nm laser ablation, the
      optical emission threshold ( approximately 2.4 GW/cm(2)) was higher than the
      ablation threshold. CONCLUSIONS: We considered that for the 1,064-nm laser
      ablation, the tissue removal was achieved through a photodisruption process at
      laser intensities of > approximately 0.8 GW/cm(2). At laser intensities of > 3.0
      GW/cm(2), however, the ablation efficiency decreased; this can be attributed to
      the absorption of incoming laser pulses by the plasma. For the 532-nm laser
      ablation, the tissue removal was achieved through a photothermal process at laser
      intensities of > approximately 1.6 GW/cm(2). At laser intensities of > 2.4
      GW/cm(2), a photodisruption process may also contribute to the tissue removal, in
      addition to a photothermal process. With regard to the ablation rates, the 1,064
      nm laser was more suitable for TMLR than the 532-nm laser. We concluded that the
      1,064-nm Q-switched Nd:YAG laser would be a potential candidate for a laser
      source for TMLR because of possible fiber-based beam delivery, its compact
      structure, cost effectiveness, and easy maintenance. Animal trials, however, have
      to be carried out to evaluate the influence of the tissue damage.

PMID- 12210599
TI  - Image cytometric bcl-2:bax and bcl-2:bcl-x ratios in invasive breast carcinoma:
      correlation with prognosis.
AB  - BACKGROUND: The bcl-2 family of proteins are important regulators of apoptosis.
      Some of the members, such as bcl-2 and bcl-x(L), inhibit cell death, whereas
      others, such as bax and bcl-x(S), promote cell death. We evaluated the ratios of
      bcl-2:bax and bcl-2:bcl-x expression by image cytometry in invasive breast
      carcinoma to determine prognostic significance. DESIGN: Five-micron sections of
      formalin-fixed, paraffin-embedded tissue from 88 invasive breast carcinomas were
      immunostained using steam antigen retrieval, an avidin biotin-complex technique
      with automated stainer and primary antibodies against bcl-2 (1/160; Dako,
      Carpenteria, CA), bax (1/1,500; PharMingen, San Diego, CA), and bcl-x (1/1,500;
      PharMingen). Positive controls were tonsil (bcl-2) and normal breast (bax and bcl
      x) tissue samples. Immunostain was measured in 15 high power fields as percentage
      positive area (PPA) in nuclei and cytoplasm using the CAS 200 image analyzer
      (Becton Dickinson, San Jose, CA). RESULTS: Median follow-up was 105 months (range
      11-130). Significantly improved disease-free survival was found in patients with
      a bcl-2:bcl-x ratio > or = 1 by univariate and multivariate analyses. The bcl
      2:bax ratio was not predictive of overall or disease-free survival. A significant
      difference in overall and disease-free survival was found between carcinomas with
      positive and negative bcl-2 expression by univariate analysis; by multivariate
      analysis, bcl-2 expression was an independent prognostic factor for disease-free
      survival. The 5-year survival rates were 77% and 50% in patients with bcl-2
      positive and bcl-2-negative carcinomas, respectively. CONCLUSION: A bcl-2:bcl-x
      ratio > or = 1, assessed by image cytometry, is significantly associated with
      improved disease-free survival in patients with invasive breast carcinoma.
      Significantly increased overall and disease-free survival is associated with
      positive bcl-2 expression.

PMID- 12210600
TI  - Determination of ploidy and steroid receptor status in breast cancer by laser
      scanning cytometry.
AB  - BACKGROUND: Measurements on DNA content and steroid receptor status in breast
      cancer are of great clinical interest. Objective determination of estrogen and
      progesterone receptor expression should help to define the lowest levels of
      positivity still responding to adjuvant antihormonal therapy. For this purpose, a
      simple protocol for laser scanning cytometry is presented. METHODS: Analysis of
      54 routine breast cancer samples was performed by laser scanning cytometry (LSC).
      To obtain single cell preparations from fresh tumor tissue, slides were prepared
      using the Cervisoft cytological device. Exact determination of tumor cell DNA
      content was done by referring to the CD45-positive tissue leukocyte fraction as
      the internal diploid reference cell population. Steroid receptor-expressing cells
      were detected by indirect immunolabeling. RESULTS: Indirect immunofluorescence
      allowed the best quantification of both the estrogen and progesterone receptor
      expressing cell fractions by LSC. The number of receptor-expressing cells could
      be given in percentage. For comparison, the 10% cutoff value was used to
      determine receptor positivity. CONCLUSION: LSC enabled a simple, reliable, and
      inexpensive determination of DNA index and steroid receptor expression in breast
      cancer specimens by objective criteria.

PMID- 12210601
TI  - Combined DNA flow cytometry and sorting with k-ras2 mutation spectrum analysis
      and the prognosis of human sporadic colorectal cancer.
AB  - BACKGROUND: Activation of the k-ras2 pathways and chromosomal instability leading
      to aneuploidy in human sporadic colorectal cancer (sCRC) is essential to the
      tumor cell ability to survive, grow, and metastatize. METHODS: The study included
      135 patients with sCRC who were followed up for a median of 72 months. Multiple
      fresh-frozen fragments obtained from superficial and invasive areas of the tumors
      were mixed and used to detect the degree of DNA aneuploidy (DNA index [DI]) and S
      phase fraction by two scatter signals and 4,6-diamidino-2-phenylindole-2
      hydrocloride (DAPI) fluorescence flow cytometry (FCM). PCR amplification and k
      ras2 mutation spectrum analysis were performed using enriched epithelial nuclei
      after sorting DNA aneuploid nuclei and DNA diploid nuclei from which tissue
      infiltrating lymphocytes were absent. RESULTS: DNA aneuploidy was detected in 98
      (73%) and k-ras2 mutations in 54 cases (40%). Univariate analyses of overall
      survival with both Dukes' A to D or B to C series of cases showed that DNA
      multiple aneuploidy, k-ras2 mutations, older age, and distal site, but not
      increased S-phase fraction, were predictive of worse outcome. Multivariate Cox
      models strongly indicated that k-ras2 mutations, but neither single nor multiple
      DNA aneuploidy, were an independent prognostic factor in both series of patients.
      In particular, with B and C Dukes' stage patients (n = 110), the relative risk
      (RR) of death was above 2.5 with k-ras2 mutations and above 3 with the G-->C/T
      transversions. CONCLUSION: Combined FCM and k-ras2 analysis may be used to
      predict long-term increased risk of death in sCRC patients.

PMID- 12210602
TI  - Immunophenotypic characterization of myelopoiesis in early and late
      myelodysplastic syndromes: use of CD44 as an aid in early diagnosis.
AB  - We investigated the possibility that myeloid cells from the bone marrow (BM) of
      myelodysplastic patients differ in their expression of CD44 antigen compared with
      expression of the antigen in normal controls. In addition, two triple-surface
      marker assays incorporating, respectively, CD44/CD33/CD66 and CD33/CD34/HLA-DR
      were used to evaluate the degree of myeloid maturation and assess the number of
      blasts in BM by flow cytometry. Patients with early-stage myelodysplastic
      syndrome (MDS; RA [FAB classification]) have significantly decreased expression
      of CD44 on gated myeloid cells. In contrast, patients with late-stage MDS (RAEB
      and RAEB-T [FAB classification]) showed an elevated expression of CD44 and an
      increased number of CD34 blasts compared with early-stage MDS patients and normal
      controls. Late-stage MDS patients also had an increase in the immature myeloid
      compartment (CD66 weak expression) compared with early-stage MDS patients and
      normal controls. We have already included this assay as part of our MDS
      evaluation protocol alongside BM morphology and cytogenetics.

PMID- 12210603
TI  - Improved flow cytometric method to enumerate residual cells: minimal linear
      detection limits for platelets, erythrocytes, and leukocytes.
AB  - Increasing demand for quality control of blood products requires more sensitive
      methods to enumerate residual cells. Presently, the reported threshold (in cells
      per microliter) is 400 for red blood cells, 30-500 for platelets, and 1 for
      leukocytes. To examine precision and linearity in enumerating residual platelets
      and red blood cells, EDTA-anticoagulated blood from healthy donors was serially
      diluted with serum, stained in TruCount tubes using a no-lyse/no-wash procedure
      and a monoclonal antibody cocktail against the CD42a (FL1) and glycophorin-A
      (FL2) epitopes, and analyzed by flow cytometry. Leukocyte counts were determined
      in separate tubes. Cell preparation and analysis were performed once for 20 blood
      samples each and 20 times using the same specimen. Acquisition from the same tube
      was performed separately for platelets (threshold on FL1) and red blood cells
      (threshold on FL2). Multiparameter analysis was used for data evaluation. Linear
      results were obtained for platelets per microliter between 3,410 and 5 and for
      red blood cells per microliter between 54,000 and 3. For the lower cell
      concentrations, the coefficient of variation was 16.7% for platelets and 10.9%
      for red blood cells. The presented method allows the distinction between
      physiologically intact and ghost red blood cells. The method represents a
      reliable, sensitive, and accurate approach to quantify platelets and red blood
      cells in diluted blood. It can be applied to enumerate residual cells in plasma
      products and meets the increasing demand for quality control in blood components.

PMID- 12210604
TI  - Mapping of antibody responses to the protective antigen of Bacillus anthracis by
      flow cytometric analysis.
AB  - BACKGROUND: Knowledge of the target and functional capability of the antibody
      response against an antigen provides more specific and relevant information about
      protective immunity than measuring the total amount of antibody produced against
      an antigen. METHODS: Using flow cytometry, a competitive assay has been created
      for measuring the antibody response against important epitopes of an antigen.
      Monoclonal antibodies (mAbs) against the protective antigen (PA) component of
      Bacillus anthracis are available that neutralize the activity of lethal toxin
      (LeTx). Flow cytometric analysis revealed that these mAbs bind PA conjugated to
      polystyrene latex microspheres. RESULTS: Unlabeled mAbs against PA competed with
      fluorescent mAbs that bind the homologous epitope but not with fluorescent mAbs
      that bind heterologous epitopes. Four-parameter logistic models were developed
      for measuring the antibody response against two epitopes of PA. Sera from anthrax
      vaccinated rabbits inhibited the binding of fluorescent mAbs to either epitope;
      the degree of inhibition correlated with the dilution of sera. CONCLUSIONS: The
      response in the rabbit sera to either epitope on PA depended on the dose of
      vaccine administered to the rabbits. No inhibition was seen with sera from
      control animals. With no species-specific components, this assay could be adapted
      readily for comparing responses between species.

PMID- 12210605
TI  - Phagocytosis of apoptotic cells assessed by flow cytometry using 7
      Aminoactinomycin D.
AB  - BACKGROUND: Apoptotic cells are recognized specifically by macrophages and are
      cleared rapidly by phagocytosis. However, the recognition mechanisms involved in
      the clearance of apoptotic cells by macrophages are still not fully understood.
      Therefore, new methods must be designed to better our understanding of the
      mechanisms of interaction between macrophages and apoptotic cells. 7
      Aminoactinomycin D (7-AAD) is a fluorescent DNA-binding stain usually used as a
      single agent to detect apoptotic cells by flow cytometry. We propose the use of 7
      AAD-stained apoptotic cells as targets for a new flow cytometry phagocytosis
      assay. METHODS: Murine T-cell lymphoma YAC-1 cells were treated with etoposide to
      induce apoptosis. Etoposide-treated YAC-1 target cells were stained subsequently
      with 7-AAD and then coincubated with resident peritoneal macrophages to allow
      phagocytosis. The samples were analyzed by flow cytometry. Macrophages that had
      phagocytosed 7-AAD-stained apoptotic cells were identified by their bright red
      fluorescence and the resulting values were expressed as the percentage of cells.
      RESULTS: The phagocytic cells appeared as a distinct population characterized by
      bright fluorescence, which could not be detected in the negative controls. The
      effects of a phagocytic enhancer (interferon-gamma [IFN-gamma]) or inhibitor
      (incubation at 4 degrees C) were assessed accurately with this flow cytometric
      method. CONCLUSIONS: We describe the use of 7-AAD in an assay that is easy and
      quick to perform. This flow cytometric-based assay allows the quantification of
      phagocytosis of apoptotic cells by macrophages.

PMID- 12210606
TI  - Confocal DNA cytometry: a contour-based segmentation algorithm for automated
      three-dimensional image segmentation.
AB  - BACKGROUND: Confocal laser scanning microscopy (CLSM) presents the opportunity to
      perform three-dimensional (3D) DNA content measurements on intact cells in thick
      histological sections. So far, these measurements have been performed manually,
      which is quite time-consuming. METHODS: In this study, an intuitive contour-based
      segmentation algorithm for automatic 3D CLSM image cytometry of nuclei in thick
      histological sections is presented. To evaluate the segmentation algorithm, we
      measured the DNA content and volume of human liver and breast cancer nuclei in 3D
      CLSM images. RESULTS: A high percentage of nuclei could be segmented fully
      automatically (e.g., human liver, 92%). Comparison with (time-consuming)
      interactive measurements on the same CLSM images showed that the results were
      well correlated (liver, r = 1.00; breast, r = 0.92). CONCLUSIONS: Automatic 3D
      CLSM image cytometry enables measurement of volume and DNA content of large
      numbers of nuclei in thick histological sections within an acceptable time. This
      makes large-scale studies feasible, whereby the advantages of CLSM can be
      exploited fully. The intuitive modular segmentation algorithm presented in this
      study detects and separates overlapping objects, also in two-dimensional (2D)
      space. Therefore, this algorithm may also be suitable for other applications.

PMID- 12210607
TI  - Optimizing and quantifying fusion of liposomes to mammalian sperm using resonance
      energy transfer and flow cytometric methods.
AB  - BACKGROUND: Liposomes are used to carry pharmaceutical agents and to alter the
      lipid composition of cell membranes. This study compared resonance energy
      transfer (RET), fluorescence dequenching, and flow cytometry as monitors and
      quantifiers of fusion between liposomes and mammalian spermatozoa. METHODS:
      Preliminary experiments used RET to determine the optimum sperm concentration for
      fusion of DL-alpha-phosphatidylcholine dipalmitoyl (PC)/DL-alpha
      phosphatidylethanolamine dipalmitoyl (PE) liposomes at 35 degrees C +/- 5 mM
      Ca2+. Microscopy confirmed the fusion of liposomes, not just adhesion (n = 3).
      Dequenching tested the time-dependent fusion of liposomes of two different lipid
      compositions to sperm, both, (n = 3) +/- 1 mM Ca2+ and (n = 3) without Ca2+ at
      two sperm concentrations. Finally, flow cytometry absolutely quantified the
      percentage of sperm fusing to liposomes at different liposome-to-sperm ratios (n
      = 4) and with sperm from different donors (n = 3). RESULTS: RET detected fusion
      of liposomes with sperm and microscopy confirmed the interaction to be true
      fusion. Dequenching detected more fusion of liposomes with sperm at 100 x 10(6)
      sperm per milliliter than at lower concentrations (P < 0.05). Fusion dynamics
      differed with lipid composition but Ca2+ had no effect. Flow cytometry reliably
      quantified the percentage of sperm fusing with liposomes, which varied from bull
      to bull (P < 0.05). CONCLUSION: Liposome fusion with mammalian sperm membranes
      can be quantified cytometrically and varies with lipid composition, sperm-to
      liposome ratio, and individual animals.

PMID- 12210608
TI  - Effects of caspase inhibition on camptothecin-induced apoptosis of HL-60 cells.
AB  - BACKGROUND: During camptothecin (CAM)-induced apoptosis of HL-60 cells, the
      external exposure of phosphatidylserine (PS) can either precede or follow DNA
      cleavage. The evidence suggests that cells in S-phase when CAM is added undergo
      rapid DNA, nuclear, and cellular disintegration before exposing PS on the outside
      of the plasma membrane, whereas cells moving from G1 into S-phase after CAM is
      added expose PS before they manifest the other phenomena. This study describes
      further investigations using the broad spectrum caspase inhibitor Z-VAD-FMK. The
      cells were cultured for a period long enough to ascertain whether a particular
      phenomenon was only delayed or was blocked completely. METHODS: Changes in cell
      light scatter, binding of annexin V-fluorescein isothiocyanate (FITC) to PS,
      uptake of propidium iodide (PI) as a measure of plasma membrane integrity, and
      DNA content after membrane fixation/permeabilization were monitored by flow
      cytometry during 24-h cultures. Fluorescence microscopy was used to examine cell
      morphology. RESULTS: Caspase inhibition blocked DNA cleavage, breakdown of the
      nuclear membrane, and formation of apoptotic bodies. It also revealed the
      existence of a CAM-activated early S-phase checkpoint. Cells arrested in early S
      phase preceded the appearance of PS-positive cells. Caspase inhibition delayed
      both PS exposure and loss of plasma membrane integrity but did not prevent
      either. CONCLUSIONS: The results support the hypothesis that the sequence of
      apoptotic phenomena in an individual CAM-treated HL-60 cell depends on the stage
      of proliferation of that cell when it encounters the CAM. They are also
      consistent with the hypothesis that caspases are not required for PS exposure or
      the loss of plasma membrane integrity, but they are involved indirectly in
      promoting these phenomena.

PMID- 12210609
TI  - Flow cytometric analyses of intraplant nuclear DNA content variation induced by
      sticky chromosomes.
AB  - BACKGROUND: In several plant species, sticky chromosomes are a consequence of
      genetic mutations or environmental effects on mitosis and meiosis. Sticky
      chromosomes result in an unequal distribution of genetic material in daughter
      cells. This unequal distribution is hypothesized to result in an increase in the
      coefficient of variation (CV) of the G1 peak of dividing cells. METHODS: The st1
      mutant and a nonmutant line in the same genetic background of maize (Zea mays L.)
      were planted in a soilless mix. A wheat (Triticum aestivum L. em thell.) line was
      grown in both low and high aluminum-saturated soil. Both plant species were
      assessed for sticky chromosomes by Feulgen-stained mitotic analysis and flow
      cytometric analysis of propidium iodide (PI)-stained G1 nuclei. RESULTS: In the
      st1 mutant, a significant increase in the number of abnormal anaphase figures was
      observed. An increase in abnormal mitotic figures was observed in wheat plants
      grown in aluminum soil. Using flow cytometry, an increase in the CV of the G1/G0
      peak was seen in the maize mutant and in wheat grown at high levels of aluminum
      saturation. This increase correlated with the number of abnormal anaphase cells
      observed. CONCLUSIONS: Flow cytometry was sensitive enough to detect the
      intraplant nuclear DNA variation associated with sticky chromosomes within a
      plant.

PMID- 12210611
TI  - Peptide mapping of proteins in human body fluids using electrospray ionization
      Fourier transform ion cyclotron resonance mass spectrometry.
AB  - Human body fluids have been rediscovered in the post-genomic era as great sources
      of biological markers and perhaps particularly as sources of potential protein
      biomarkers of disease. Analytical tools that allow rapid screening, low sample
      consumption, and accurate protein identification are of great importance in
      studies of complex biological samples and clinical diagnosis. Mass spectrometry
      is today one of the most important analytical tools with applications in a wide
      variety of fields. One of the fastest growing applications is in proteomics, or
      the study of protein expression in an organism. Mass spectrometry has been used
      to find post-translational modifications and to identify key functions of
      proteins in the human body. In this study, we review the use of human body fluids
      as sources for clinical markers and present new data that show the ability of
      Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) to
      identify and characterize proteins in four human body fluids: plasma,
      cerebrospinal fluid (CSF), saliva, and urine. The body fluids were tryptically
      digested without any prior separation, purification, or selection, and the digest
      was introduced into a 9.4 T FTICR mass spectrometer by direct-infusion
      electrospray ionization (ESI). Even though these samples represent complex
      biological mixtures, the described method provides information that is comparable
      with traditional 2D-PAGE data. The sample consumption is extremely low, a few
      microliters, and the analysis time is only a few minutes. It is, however, evident
      that the separation of proteins and/or peptides must be included in the
      methodology, in order to detect low-abundance proteins and other proteins of
      biological relevance.

PMID- 12210612
TI  - Threshold photoionization in time-of-flight mass spectrometry.
AB  - Multi-photon excitation in a time-of-flight mass spectrometer (TOF-MS) is shown
      to lead to threshold ions with defined internal energy. A powerful technique for
      the production of threshold ions is based on the excitation of high long-lived
      Rydberg states embedded in the ionization continuum. The Rydberg molecules are
      separated with suitable separation techniques from ions produced by a direct
      multi-photon ionization process. Finally, the ionization of the Rydberg molecules
      in a delayed pulsed electric field leads to threshold ions. This work reviews
      several separation techniques, and reports on applications of threshold
      ionization for investigation of the structure, energetics, and dynamics of
      neutral molecules, molecular cations, and cluster cations.

PMID- 12210613
TI  - Studies of biomolecular conformations and conformational dynamics by mass
      spectrometry.
AB  - In the post-genomic era, a wealth of structural information has been amassed for
      proteins from NMR and crystallography. However, static protein structures alone
      are not a sufficient description: knowledge of the dynamic nature of proteins is
      essential to understand their wide range of functions and behavior during the
      life cycle from synthesis to degradation. Furthermore, few proteins have the
      ability to act alone in the crowded cellular environment. Assemblies of multiple
      proteins governed by complex signaling pathways are often required for the tasks
      of target recognition, binding, transport, and function. Mass spectrometry has
      emerged over the past several years as a powerful tool to address many of these
      questions. Recent improvements in "soft" ionization techniques have enabled
      researchers to study proteins and biomolecular complexes, both directly and
      indirectly. Likewise, continuous improvements in instrumental design in recent
      years have resulted in a dramatic expansion of the m/z range and resolution,
      enabling observation of large multi-protein assemblies whose structures are
      retained in the gas phase. In this article, we discuss some of the mass
      spectrometric techniques applied to investigate the nature of the conformations
      and dynamical properties that govern protein function.

PMID- 12210615
TI  - A Bayesian fixed effects analysis of the Mantel-Haenszel model applied to meta
      analysis.
AB  - When performing a meta analysis, it is often necessary to combine results from
      several 2 x 2 contingency tables. The Mantel-Haenszel model assumes a common
      measure of association between the treatment and outcome variables across the
      tables. A Bayesian method is described for drawing inferences regarding the
      measure of association, for checking the plausibility of the Mantel-Haenszel
      model, and for drawing inferences regarding the success rates for the individual
      studies. While the methodology is readily extendable to random effects models, a
      fixed effects approach avoids the complex statistical modelling of a mixture
      distribution which is required for the good application of random effects models.

PMID- 12210616
TI  - Network meta-analysis for indirect treatment comparisons.
AB  - I present methods for assessing the relative effectiveness of two treatments when
      they have not been compared directly in a randomized trial but have each been
      compared to other treatments. These network meta-analysis techniques allow
      estimation of both heterogeneity in the effect of any given treatment and
      inconsistency ('incoherence') in the evidence from different pairs of treatments.
      A simple estimation procedure using linear mixed models is given and used in a
      meta-analysis of treatments for acute myocardial infarction.

PMID- 12210617
TI  - Fixed-effect versus random-effect models for evaluating therapeutic preferences.
AB  - A preference trial is a special form of cross-over trial where clinical
      conditions determine when patients change treatment, in a prescribed order. This
      leads to binary responses with variable lengths. In cross-over trials with normal
      responses, patient effect may be treated as either fixed or random. However, with
      binary responses, random- and fixed-effect assumptions may lead to very different
      conclusions, so that one is no longer an alternative to the other.

PMID- 12210618
TI  - Periodograms and pulse detection methods for pulsatile hormone data.
AB  - Pulse detection algorithms and spectral analysis are the two most common methods
      for analysing pulsatile hormone data. We compared a popular high quality pulse
      detection algorithm (CLUSTER) to spectral analysis on a data set comparing
      luteinizing hormone data in depressed and control women. For these data,
      periodogram analysis methods, in particular Fisher's periodicity test, were
      superior in distinguishing the groups. Extending the pulse detection method to
      include measures of intra-individual variability improved its discriminatory
      performance. The two methods complement each other.

PMID- 12210619
TI  - Prediction of the long-term survival in breast cancer patients according to the
      present oncological status.
AB  - After a breast cancer diagnosis, single or multiple events can occur during
      follow-up (recurrence, metastasis, and death). An analysis of long-term survival
      should take into account not only the initial characteristics of the patient, but
      also her oncological status (that is, her history) after surgery. For this
      purpose, we used a technique proposed by Klein, Keiding and Copelan (1994), to
      predict the probability of a patient being alive 20 years after surgery for a
      breast cancer, based on data concerning her oncological status at time t. The
      first step of the model was to estimate the hazard function for each event of
      interest (recurrence, metastasis, and death) in a Cox model including initial
      patient characteristics (age, tumour size, number of involved axillary lymph
      nodes and the Scarff, Bloom and Richardson (SBR) histo-prognostic grade) and time
      dependent covariates representing the occurrence of intermediate events
      (recurrence and metastasis). The second step was to use these estimations to
      calculate the conditional probability of being alive 20-t years later for a
      patient, given her oncological status at time t (t<10 years). In this second
      step, the method presented by Klein, Keiding and Copelan was extended to include
      non-proportional hazards. This model has been applied to a population of 3180
      patients operated on for a breast cancer at the Institut Gustave Roussy between 1
      January 1954 and 31 December 1983. At the time of surgery, the probability of
      survival at 20 years is 0.78 for all patients. Ten years after surgery, if no
      recurrence or metastasis are observed, the probability of survival at 20 years
      will rise to 0.89. If only a recurrence is observed, the probability of a patient
      being alive at 20 years will drop to 0.72. If a metastasis and no recurrence is
      observed, the probability of survival at 20 years will be only 0.18. If both
      recurrence and metastasis are observed the probability of survival at 20 years
      will be equal to 0.09. In conclusion, the model used dynamically appraises the
      prognosis and represents a new approach for studying the outcome of breast cancer
      patients having undergone surgery.

PMID- 12210620
TI  - Estimation of the time-dependent vaccine efficacy from a measles epidemic.
AB  - We present a method to estimate the time-dependent vaccine efficacy from the
      cohort-specific vaccination coverage and from data on the vaccination status of
      cases and apply it to a measles epidemic in Germany which involved 529 cases, 88
      of whom were vaccinated and 370 unvaccinated (for the remaining 71 cases the
      vaccination status is unknown). Our epidemiological model takes into account that
      maternal antibodies prevent successful vaccination and that vaccine immunity may
      be lost over time. Model parameters are estimated from the data using maximum
      likelihood. Vaccination coverage, as determined in school surveys, ranged from
      27.6 per cent for the cohort born in 1974 to 85 per cent for the 1986 cohort,
      which is far too low to prevent measles transmission. Cohorts for which no school
      surveys were performed are omitted from analysis. Thus, sufficient data are
      available for only 282 cases, 69 of whom are vaccinated. According to our
      estimates, measles vaccinations provided no immunity before 1978 (95 per cent CI:
      0 to 47 percent), for the period 1978-1982, the estimated vaccine efficacy was 80
      percent (95 percent CI: 67 to 89 percent), and for 1982-1990 it was 97 percent
      (95 percent CI: 93 to 99 percent). After 1990, the estimated value dropped to 89
      per cent, but its confidence interval widely overlaps with that of the previous
      period (95 percent CI: 74 to 97 percent). Loss of immunity was estimated to be
      zero (95 percent CI: 0 to 0.003/year). Several sensitivity analyses were
      performed with respect to the model assumptions. A modified model which assumed
      constant efficacy at all vaccination times yielded a high estimate of 96 per cent
      (95 percent CI: 92 to 98 percent) for primary vaccine efficacy but also a high
      loss rate of immunity of 0.007/year (95 percent CI: 0.001 to 0.012) to explain
      the high fraction of vaccinated cases among older individuals. The likelihood
      score value is however significantly inferior compared to the score value of the
      model with time-dependent vaccine efficacy.

PMID- 12210622
TI  - Evaluating serial observations of precancerous lesions for further study as a
      trigger for early intervention.
AB  - Many long-term studies of the early detection of cancer involve serial
      observations of precancerous lesions and information as to whether or not the
      subject was diagnosed with cancer during the study period. Often the purpose of
      these studies is to decide whether or not the precancerous lesion should be
      studied in a future trial as a trigger for early intervention. A general approach
      to the analysis of cancer biomarkers is to estimate false and true positive rates
      to determine if they fall in the target region of those false and true positives
      that indicate promise for further study. The challenge with analysing serial data
      on precancerous lesions is estimating false and true positive rates when the
      number of observations varies among subjects. To solve this problem, we propose a
      Markov chain model in reverse time. The methodology is illustrated using serial
      observations of precancerous lesions found on sputum cytology.

PMID- 12210621
TI  - Maximum likelihood estimation in the joint analysis of time-to-event and multiple
      longitudinal variables.
AB  - Joint modelling of longitudinal and survival data has received much attention in
      recent years. Most have concentrated on a single longitudinal variable. This
      paper considers joint modelling in the presence of multiple longitudinal
      variables. We explore direct association of time-to-event and multiple
      longitudinal processes through a frailty model and use a mixed effects model for
      each of the longitudinal variables. Correlations among the longitudinal variables
      are induced through correlated random effects. We allow effects of categorical
      and continuous covariates on both longitudinal and time-to-event responses and
      explore interactions between the longitudinal variables and other covariates on
      time-to-event. Estimates of the parameters are obtained by maximizing the joint
      likelihood for the longitudinal variable processes and the event process. We use
      a one-step-late EM algorithm to handle the direct dependence of the event process
      on the modelled longitudinal variables along with the presence of other fixed
      covariates in both processes. We argue that such a joint analysis with multiple
      longitudinal variables is advantageous to one with only a single longitudinal
      variable in revealing interplay among multiple longitudinal variables and the
      time-to-event.

PMID- 12210623
TI  - Penalized likelihood approach to estimate a smooth mean curve on longitudinal
      data.
AB  - This paper aims to propose a penalized likelihood approach to estimate a smooth
      mean curve for the evolution with time of a Gaussian variable taking into account
      the correlation structure of longitudinal data. The model is an extension of the
      mixed effects linear model including an unspecified function of time f(t). The
      estimator (circumflex)f(t) is defined as the solution of the maximization of the
      penalized likelihood and is approximated on a basis of cubic M-spline with a
      reduced number of knots. We present modifications of four criteria (cross
      validation, generalized cross-validation, T of Rice, Akaike's criterion) to
      estimate the smoothing parameter when data are correlated; these four criteria
      gave very similar results in the simulation study. The simulation study showed
      also the superiority of the Bayesian confidence bands of the mean curve over the
      frequentist ones. We develop empirical Bayes estimates of subject-specific
      deviations. This approach was applied to study the progression of CD4+ lymphocyte
      counts in a cohort of HIV patients treated with protease inhibitors.

PMID- 12210624
TI  - An application of the technique of density estimation in geographical
      epidemiology of goitre in the Muzaffarpur district of Bihar state of India.
AB  - The Gangetic plains in the Sub-Himalayan belt of India are known endemic areas
      for goitre. The districts of Muzaffarpur and Sitamarhi in the eastern zone in the
      Bihar state of India showed a prevalence of over 30 per cent of goitre in a
      survey conducted by the Indian Council of Medical Research (ICMR) during 1983
      1986. In the present paper, the technique of density estimation is employed to
      estimate the probability density functions of goitre-affected and normal (non
      goitre) populations of the district of Muzaffarpur. The likelihood ratio is then
      plotted against distance of the villages from the Indo-Nepal border keeping their
      distances from the headquarters in the district of Sitamarhi at fixed level.
      Using the odds form of Bayes rule, the posterior odds of goitre are calculated
      and compared at two given points.

PMID- 12210625
TI  - A solution to the problem of separation in logistic regression.
AB  - The phenomenon of separation or monotone likelihood is observed in the fitting
      process of a logistic model if the likelihood converges while at least one
      parameter estimate diverges to +/- infinity. Separation primarily occurs in small
      samples with several unbalanced and highly predictive risk factors. A procedure
      by Firth originally developed to reduce the bias of maximum likelihood estimates
      is shown to provide an ideal solution to separation. It produces finite parameter
      estimates by means of penalized maximum likelihood estimation. Corresponding Wald
      tests and confidence intervals are available but it is shown that penalized
      likelihood ratio tests and profile penalized likelihood confidence intervals are
      often preferable. The clear advantage of the procedure over previous options of
      analysis is impressively demonstrated by the statistical analysis of two cancer
      studies.

PMID- 12210627
TI  - A comment on replication, p-values and evidence, S.N.Goodman, Statistics in
      Medicine 1992; 11:875-879.

PMID- 12210626
TI  - A weighted estimating equation for linear regression with missing covariate data.
AB  - Linear regression is one of the most popular statistical techniques. In linear
      regression analysis, missing covariate data occur often. A recent approach to
      analyse such data is a weighted estimating equation. With weighted estimating
      equations, the contribution to the estimating equation from a complete
      observation is weighted by the inverse 'probability of being observed'. In this
      paper, we propose a weighted estimating equation in which we wrongly assume that
      the missing covariates are multivariate normal, but still produces consistent
      estimates as long as the probability of being observed is correctly modelled. In
      simulations, these weighted estimating equations appear to be highly efficient
      when compared to the most efficient weighted estimating equation as proposed by
      Robins et al. and Lipsitz et al. However, these weighted estimating equations, in
      which we wrongly assume that the missing covariates are multivariate normal, are
      much less computationally intensive than the weighted estimating equations given
      by Lipsitz et al. We compare the weighted estimating equations proposed in this
      paper to the efficient weighted estimating equations via an example and a
      simulation study. We only consider missing data which are missing at random; non
      ignorably missing data are not addressed in this paper.

PMID- 12210629
TI  - Meta-analysis combining parallel and cross-over clinical trials. I: Continuous
      outcomes.
AB  - Among clinical trials assessing a given treatment, often parallel and cross-over
      designs are used together. In the first paper of a series of three, we explore
      two methods to pool continuous outcomes in a meta-analysis combining parallel and
      cross-over trial designs: the weighted mean difference (WMD) and the standardized
      weighted mean difference (SWMD). The combined design meta-analytic formulae are
      based on a weighted average of the two design treatment estimates. A random
      effects model can be implemented. Both WMD and SWMD can be used, the choice of
      the method is determined by the type of outcomes obtained in the trials. Compared
      to the number of included subjects, the relative weight of the cross-over design
      is large in combined-design meta-analysis. Differences in the weight estimation
      between WMD and SWMD can also accentuate the relative weight of cross-over
      trials, which must be considered a case of design-specific bias.

PMID- 12210630
TI  - Meta-analysis combining parallel and cross-over clinical trials. II: Binary
      outcomes.
AB  - We examine different methods to pool binary outcomes used both in parallel and
      cross-over trials. Odds ratio (OR) estimators obtained from joint conditional
      probabilities in cross-over trials, such as the Mantel-Haenszel and Peto methods,
      are compared to an OR estimator using marginal results of cross-over trials. When
      there is correlation between the outcomes in the two cross-over periods, joint
      conditional ORs differ from marginal ORs and cannot be combined with OR estimates
      from parallel trials. The marginal OR estimate is independent of the between
      period correlation and it includes a correction for cross-over correlation in the
      variance estimate. As its computation is similar in cross-over and parallel
      trials, it is the method of choice to pool results from parallel and cross-over
      trials in a combined design meta-analysis.

PMID- 12210631
TI  - Meta-analysis combining parallel and cross-over clinical trials. III: The issue
      of carry-over.
AB  - In meta-analysis combining results from parallel and cross-over trials, there is
      a risk of bias originating from the carry-over effect in cross-over trials. When
      pooling treatment effects estimated from parallel trials and two-period two
      treatment cross-over trials, meta-analytic estimators of treatment effect can be
      obtained from the combination of parallel trial results either with cross-over
      trial results based on data of the first period only or with cross-over trial
      results analysed with data from both periods. Taking data from the first cross
      over period protects against carry-over but gives less efficient treatment
      estimators and may lead to selection bias. This study evaluates in terms of
      variance reduction and mean square error the cost of calculating meta-analysis
      estimates with data from the first period instead of data from the two cross-over
      periods. If the information on cross-over sequence is available, we recommend
      performing two combined design meta-analyses, one using the first cross-over
      period data and one based on data from both cross-over periods. To investigate
      simultaneously the statistical significance of these two estimators as well as
      the carry-over at meta-analysis level, a method based on a multivariate analysis
      of the meta-analytic treatment effect and carry-over estimates is proposed.

PMID- 12210632
TI  - Flexible parametric proportional-hazards and proportional-odds models for
      censored survival data, with application to prognostic modelling and estimation
      of treatment effects.
AB  - Modelling of censored survival data is almost always done by Cox proportional
      hazards regression. However, use of parametric models for such data may have some
      advantages. For example, non-proportional hazards, a potential difficulty with
      Cox models, may sometimes be handled in a simple way, and visualization of the
      hazard function is much easier. Extensions of the Weibull and log-logistic models
      are proposed in which natural cubic splines are used to smooth the baseline log
      cumulative hazard and log cumulative odds of failure functions. Further
      extensions to allow non-proportional effects of some or all of the covariates are
      introduced. A hypothesis test of the appropriateness of the scale chosen for
      covariate effects (such as of treatment) is proposed. The new models are applied
      to two data sets in cancer. The results throw interesting light on the behaviour
      of both the hazard function and the hazard ratio over time. The tools described
      here may be a step towards providing greater insight into the natural history of
      the disease and into possible underlying causes of clinical events. We illustrate
      these aspects by using the two examples in cancer.

PMID- 12210633
TI  - A Bayesian approach to parameter estimation in HIV dynamical models.
AB  - In the context of a mathematical model describing HIV infection, we discuss a
      Bayesian modelling approach to a non-linear random effects estimation problem.
      The model and the data exhibit a number of features that make the use of an
      ordinary non-linear mixed effects model intractable: (i) the data are from two
      compartments fitted simultaneously against the implicit numerical solution of a
      system of ordinary differential equations; (ii) data from one compartment are
      subject to censoring; (iii) random effects for one variable are assumed to be
      from a beta distribution. We show how the Bayesian framework can be exploited by
      incorporating prior knowledge on some of the parameters, and by combining the
      posterior distributions of the parameters to obtain estimates of quantities of
      interest that follow from the postulated model.

PMID- 12210634
TI  - Robustness of choice of number of doses for maximum likelihood estimation of the
      ED(50) in bioassay.
AB  - A number of studies have looked at the choice of number of doses for estimating
      the median effective dose (ED(50)) when the form of a dose-response curve is
      correctly assumed (see, for example, Muller and Schmitt, 1990). Here we address
      the question of the robustness of number of doses chosen using Muller and
      Schmitt's method when a logistic dose-response curve is incorrectly assumed. The
      underlying true dose-response curves considered include the probit, cubic
      logistic and Aranda-Ordaz asymmetric models. The simulation results show that,
      for the above true dose-response curves and the uniform design density with doses
      spaced symmetrically or slightly asymmetrically around the assumed ED(50),
      choosing as many doses as possible either minimizes the mean squared error (MSE)
      or produces a MSE chosen to the minimum.

PMID- 12210635
TI  - Potential of feature selection methods in heart rate variability analysis for the
      classification of different cardiovascular diseases.
AB  - In this study heart rate variability (HRV) analysis was applied to characterize
      patients suffering from coronary heart disease (CHD), dilated cardiomyopathy
      (DCM) and patients who had survived an acute myocardial infarction (MI). On the
      basis of several HRV parameters, an optimal discrimination between the different
      kinds of cardiovascular diseases and between the diseases and healthy controls
      (HC) was derived by feature selection and linear classification. For each task a
      small favourable subset of a set of 33 potentially interesting HRV measures was
      selected with the intention of improving the diagnostic value and facilitating
      the physiological interpretation of HRV analysis. Time- and frequency-domain
      parameters as well as parameters from non-linear dynamics were included in the
      analysis. With the expectation that different diseases are characterized by
      different phenomena, feature selection was applied for each task separately.
      Using the features optimal for one task to another task can reveal a loss in
      performance, but it turned out that one specific parameter set (set1: normalized
      low frequency LF/P and a non-linear variability measure WPSUM13) was applicable
      for all tasks, where diseased and healthy subjects have to be distinguished,
      without significant reduction in performance. This set seems to be a general
      marker for pathologic changes in HRV and might be used for early detection of
      heart diseases. The classification between different heart diseases requires
      another parameter set (set2: meanNN and sdaNN, reflecting the steady state
      behaviour of the heart rate and long and short term SEAR describing the spectral
      composition). However, the use of set1 for the separation of different kinds of
      diseases, where set2 is appropriate, led to significant reduction in performance
      and vice versa. This observation may be important for future developments of HRV
      measures especially suitable for the assessment of disease severity.

PMID- 12210636
TI  - On the issue of 'multiple' first failures in competing risks analysis.
AB  - In the classical competing risks framework, a subject may only fail from one of
      several distinct causes. However, in the context of cancer clinical trials where
      information on first relapse is usually of interest, there could be occasions
      when 'multiple' first recurrences are identified at a particular follow-up. In
      this instance, the competing risks methodology cannot be implemented without
      first tackling the issue of 'tied' first failure. When the tied events were
      substantial, Arriagada et al. regarded each competing failure separately, and
      combined the 'simultaneous' failures into a single category for analysis. This
      paper describes two other methods of accounting for 'multiple' failures. First,
      the ties were dealt with by applying a weighting factor which was equal to the
      reciprocal of the number of ties. We also considered 'jittering' which randomly
      adds or subtracts a small number to each 'tied' event time to randomly break the
      tie. As illustrated using the data obtained from a randomized trial of patients
      with operable osteosarcoma, the estimates based on Arriagada's approach have
      larger standard errors. Estimates from the other alternative methods were
      similar. Multiple jittering has the advantage of wide applicability in any
      situation of tied survival times. However, it takes a longer computer running
      time, especially when the number of replicates is large. The weighted Cox
      approach is the method of choice where statistical software allows its
      implementation without extra programming effort.

PMID- 12210637
TI  - A three-dimensional model for the tooth-loss patterns by multi-plane regression
      analysis.
AB  - The construction of dental condition models is one of the useful methods for
      analysis of epidemiological surveys. The purpose of this investigation was to
      make a simple model with clear turning points for the longitudinal tooth-loss
      patterns of Japanese adults by means of multi-plane regression analysis. Since
      1957, the Japanese Ministry of Health and Welfare has carried out national
      surveys of dental conditions every six years. The data of present tooth numbers
      by age (24-79 years) and sex from these surveys were used for this study. When
      there are turning points between two variables, intersecting straight lines
      regression is a valid means. However, a new method was developed so that the data
      of this study had three variables. The new three-dimensional model by multi-plane
      regression analysis seemed to fit tooth-loss patterns of Japanese adults within
      three phases. Younger subjects are represented in the first phase followed by the
      third phase of elders, where tooth loss was rather slow. However, in the second
      phase, middle-aged subjects, people lost their teeth rapidly. Thus, prolongation
      of the first phase could be an important factor to improve overall dental health.

PMID- 12210638
TI  - Disease prevalence estimations based on contact registrations in general
      practice.
AB  - This paper describes how to estimate the prevalence of chronic diseases in a
      population using data from contact registrations in general practice with a
      limited time length. Instead of using only total numbers of observed patients
      adjusted for the length of the observation period, we propose the use of (i) the
      time of the first contact of patients, (ii) the joint total numbers of patients
      and contacts, and (iii) the sets of patients in distinct time intervals, to
      generate prevalence rate estimates. The three new prevalence rate estimators have
      been developed assuming either a homogeneous or a parameterized heterogeneous
      patient population. Systematic and stochastic components of the estimators have
      been analysed by cross-validation for five chronic diseases using data from the
      Dutch 'Study on Chronic Conditions'. The results show that the first two
      estimators work well for diseases with a relatively structured visiting
      behaviour, such as hypertension and diabetes mellitus, assuming a time-constant
      contact rate and homogeneous patient population. For diseases such as ischaemic
      heart disease, chronic non-specific respiratory diseases and osteoarthritis, that
      do not satisfy these assumptions, the methods generally result in
      underestimations.

PMID- 12210639
TI  - Sympercents: symmetric percentage differences on the 100 log(e) scale simplify
      the presentation of log transformed data.

PMID- 12210640
TI  - Comorbidity between eating disorders and anxiety disorders: a review.
AB  - OBJECTIVE: We conducted a critical literature review on studies assessing the
      prevalence of anxiety disorders (AD) in subjects with eating disorders (ED)
      (anorexia nervosa and bulimia nervosa). In the first part, we discuss
      methodological issues relevant to comorbidity studies between ED and AD. In the
      second part, taking into account these methodological considerations raised, we
      summarize the findings of these studies. METHOD: We performed a manual and
      computerized search (Medline) for all published studies on comorbidity between ED
      and AD, limiting our search from 1985-2001 to get sufficiently homogeneous
      diagnostic criteria for both categories of disorders. RESULTS: Too few studies
      include control groups and few studies have compared diagnostic subgroups of ED
      subjects, with scarce or conflicting results. DISCUSSION: We discuss the results
      taking into account the methodological problems observed. We give guidelines for
      reviewing the results of published studies and planing future research.

PMID- 12210641
TI  - A randomized secondary treatment study of women with bulimia nervosa who fail to
      respond to CBT.
AB  - OBJECTIVE: Since the description of bulimia nervosa as a distinct diagnostic
      entity in 1979, several psychological and pharmacological interventions have been
      developed and empirically tested. The existence of several effective treatments,
      none of which is completely effective, is common to most psychiatric conditions.
      The research question that flows from such findings is whether second-level
      treatments would be effective for those who fail initial treatment. METHOD: In
      the case of bulimia nervosa, the research findings suggest that cognitive
      behavioral therapy (CBT) is the first level of treatment and that both
      antidepressant medication and interpersonal psychotherapy (IPT) may potentially
      be effective second-level treatments. This was a multicenter study in which 194
      patients were initially treated with CBT. Those treated unsuccessfully (n = 62)
      were then randomized to treatment with IPT or medication management. RESULTS: Of
      those assigned to secondary treatment, 37 completed such treatment and 25 dropped
      out or were withdrawn. The abstinence rate for subjects assigned to treatment
      with IPT was 16% and for those assigned to medication management was 10%. No
      significant differences were found between medication and IPT in either the
      intent-to-treat or completer analysis. DISCUSSION: Dropout rates were high, and
      response rates were low among BN patients assigned to secondary treatments who
      failed to achieve remission with CBT. Offering lengthy sequential treatments
      appears to have little value, and alternative models for therapy need to be
      tested.

PMID- 12210642
TI  - Prospective predictors of the onset of anorexic and bulimic syndromes.
AB  - OBJECTIVE: This study investigated prospective predictors of lifetime history
      diagnoses of partial- and full-syndrome anorexia nervosa and bulimia nervosa
      (referred to as anorexic syndrome and bulimic syndrome.) METHOD: Participants
      were 157 females who were studied initially in the 7th-10th grades (ages 12-16)
      and followed-up 2 and 8 years later in middle adolescence (ages 14-18) and young
      adulthood (ages 20-24), respectively. A telephone interview to determine lifetime
      history of anorexic and bulimic syndromes was conducted in young adulthood.
      RESULTS: In multivariate analyses controlling for initial eating symptoms,
      initial perfectionism and low body weight predicted young adult onset of anorexic
      syndrome, and initial negative emotion predicted young adult onset of bulimic
      syndrome. DISCUSSION: Our findings suggest that adolescent girls who are
      initially thin and also adhere to perfectionistic standards may be at risk for
      developing anorexic syndrome. For bulimia, negative affect may contribute to the
      development of the binge-purge cycle.

PMID- 12210643
TI  - Body dysmorphic disorder in patients with anorexia nervosa: prevalence, clinical
      features, and delusionality of body image.
AB  - OBJECTIVE: The prevalence of body dysmorphic disorder in patients with anorexia
      nervosa is unknown. We hypothesized that body dysmorphic disorder would be
      underdiagnosed in patients with anorexia nervosa and that comorbidity with body
      dysmorphic disorder would result in greater overall dysfunction. METHOD: Forty
      one patients with DSM-IV anorexia nervosa completed the Body Dysmorphic Disorder
      Questionnaire, a self-report screen for body dysmorphic disorder. A follow-up
      interview was conducted using a reliable clinician-administered semistructured
      diagnostic instrument for DSM-IV body dysmorphic disorder. Delusionality about
      appearance was assessed using a validated semistructured interview. Comorbid DSM
      IV diagnoses, number of hospitalizations and suicide attempts were obtained by
      means of a detailed diagnostic interview. RESULTS: Sixteen (39%) of the 41
      patients with anorexia nervosa were diagnosed with comorbid body dysmorphic
      disorder unrelated to weight concerns. The anorexia nervosa patients with body
      dysmorphic disorder had significantly lower overall functioning and higher levels
      of delusionality than the anorexic patients without body dysmorphic disorder.
      DISCUSSION: These preliminary results suggest that body dysmorphic disorder may
      be relatively common among patients with anorexia nervosa. The presence of
      comorbid body dysmorphic disorder may indicate a more severe form of illness.

PMID- 12210644
TI  - Fractures in patients with anorexia nervosa, bulimia nervosa, and other eating
      disorders--a nationwide register study.
AB  - OBJECTIVE: To study fracture risk in patients with anorexia nervosa (AN), bulimia
      nervosa (BN), or eating disorders not otherwise specified (EDNOS). METHOD: Cohort
      study including all Danes diagnosed with AN (n = 2,149), BN (n = 1,294), or EDNOS
      (n = 942) between 1977 and 1998. Each patient was compared with three randomly
      drawn age- and gender-matched control subjects. RESULTS: Fracture risk was
      increased in AN after diagnosis compared to controls (incidence rate ratio: 1.98,
      95% CI: 1.60-2.44), but not before. The increased fracture risk persisted more
      than 10 years after diagnosis. A significant increase in fracture risk was found
      before diagnosis in BN (1.31, 95% CI: 1.04-1.64), with a trend towards an
      increase after diagnosis (1.44, 95% CI: 0.93-2.22). EDNOS patients had a
      significant increase in fracture risk before (1.39, 95% CI: 1.06-1.81) and after
      diagnosis (1.77, 95% CI: 1.25-2.51). DISCUSSION: The increased fracture risk many
      years after diagnosis indicates permanent skeletal damage.

PMID- 12210645
TI  - Full syndromal versus subthreshold anorexia nervosa, bulimia nervosa, and binge
      eating disorder: a multicenter study.
AB  - OBJECTIVE: The diagnostic criteria for anorexia nervosa (AN), bulimia nervosa
      (BN), and binge eating disorder (BED) establish symptom severity levels, which
      are used to separate full cases from partial cases. However, the value of these
      distinctions is unclear. METHOD: Three hundred eighty-five women with full or
      partial AN, BN, or BED were assessed at entry into a longitudinal study of eating
      disorders. RESULTS: Stepwise discriminant analysis revealed that full and partial
      BN were discriminated by the Yale-Brown-Cornell Eating Disorders Scale total
      scores (kappa =.46). However, it was not possible to discriminate between full
      and partial AN or BED. Discriminant analysis also demonstrated clear differences
      between full AN, BN, and BED. DISCUSSION: Full BN can be differentiated from
      partial BN by more severe eating disorder symptoms, whereas both full and partial
      AN and full and partial BED appear quite similar. These results emphasize the
      distinct nature of AN, BN, and BED, as well as the similarities between full and
      partial cases.

PMID- 12210646
TI  - Restoration of ovarian and uterine maturity in adolescents with anorexia nervosa.
AB  - OBJECTIVE: To determine the optimal weight-to-height ratio to achieve maturity of
      the reproductive organs when visualized by pelvic ultrasound in adolescent girls
      with anorexia nervosa. To examine the distribution of weight-to-height ratios in
      the group of adolescents in whom pelvic maturity was attained. METHODS:
      Adolescent girls with anorexia nervosa received serial transabdominal pelvic
      ultrasound scans as they regained weight. A record of their weight-to-height
      ratio had been noted on each occasion. The scans were defined as mature or
      immature using strict criteria. RESULTS: There was a wide range of weight-to
      height ratios in both the mature and immature groups of patients with a
      considerable overlap between the groups. However, 88% of the sample required a
      weight-to-height ratio of 100% (body mass index [BMI] 20) to achieve reproductive
      maturity. CONCLUSION: Previous target weights have been too low to ensure
      reproductive maturity. The resulting hypoestrogenic state increases the risk of
      future osteoporosis. Pelvic ultrasound is the safest and most reliable method for
      determining ovarian and uterine maturity in adolescent girls with anorexia
      nervosa.

PMID- 12210647
TI  - Similarities and differences between Caucasian and African American college women
      on eating and dieting expectancies, bulimic symptoms, dietary restraint, and
      disinhibition.
AB  - OBJECTIVE: To clarify race differences in eating disorder risk factors and
      symptoms, by comparing Caucasian and African American samples on the factor
      structures, intercorrelations, and mean levels of endorsement on a set of risk
      and symptom measures. METHOD: A sample of 300 Caucasian and 200 African American
      undergraduates completed measures of eating and thinness/dieting expectancies,
      the Three-Factor Eating Questionnaire (TFEQ), and the BULIT. RESULTS: The factor
      structures of each measure were invariant across race. Intercorrelations among
      the measures generally did not differ across race. On the three expectancy
      measures predictive of symptomatology, two of three scales of the TFEQ, and the
      BULIT, African American women had lower mean scores than Caucasian women.
      Socioeconomic status did not account for the results: in this sample, it was
      unrelated to race and correlated with only 1 of 20 measures. DISCUSSION: The
      factor-based meaning of these measures appears to be consistent across race. The
      measures correlate similarly across race, suggesting that the risk process may be
      similar for both races, but African American women endorsed significantly fewer
      risk factors and fewer symptoms.

PMID- 12210648
TI  - Eating and body image disturbances in adolescent psychiatric inpatients: gender
      and ethnicity patterns.
AB  - OBJECTIVE: To examine gender and ethnicity patterns in eating and body image
      disturbances in adolescents hospitalized in a psychiatric facility. METHOD:
      Participants comprised 715 inpatients who completed the Millon Adolescent
      Clinical Inventory. Gender (317 males, 398 females), ethnicity (553 Caucasians,
      77 Latino Americans, 85 African Americans), and Gender x Ethnicity interactions
      in the features of eating disorders and body image disturbance were explored in
      the study group. RESULTS: Eating-related disturbances at diagnostic threshold
      were infrequent but participants' reported rates of specific features and
      symptoms were not. Overall, a significantly higher proportion of females than
      males reported features of eating and body image disturbances. The three ethnic
      groups differed significantly in their reports of body image disturbances but not
      in their endorsement of features of eating disorders. Post-hoc comparisons
      revealed that a significantly higher proportion of Caucasian participants
      reported body image concerns than did African American and Latino American
      participants who did not differ significantly from one another. Significant
      Gender x Ethnicity interactions were observed, with Caucasian females endorsing
      higher rates of features of eating disorders and body image disturbances than
      African American and Latino American females. DISCUSSION: In adolescent
      psychiatric inpatients, although Caucasian females report the highest rates of
      the features of eating and body image disturbances, such concerns are not
      uncommon in males and in minorities.

PMID- 12210649
TI  - Beyond shape and weight: exploring the relationship between nonbody determinants
      of self-esteem and eating disorder symptoms in adolescent females.
AB  - OBJECTIVE: Recent research using the Shape and Weight-Based Self-Esteem (SAWBS)
      Inventory has shown that basing self-esteem on shape and weight is related to
      eating disorder and psychiatric symptoms. This study examined the relationship
      between other determinants of self-esteem assessed in the SAWBS Inventory (e.g.,
      friendships, intimate relationships, school/work competence) and eating disorder
      and psychological health variables. METHOD: Female high school adolescents (N =
      235) participated in this study. The relative contribution of the self-esteem
      dimensions to eating disorder and self-esteem was examined. RESULTS: In addition
      to shape and weight, basing self-esteem on intimate relationships was also
      related to higher eating disorder symptoms and lower body and global self-esteem.
      The only protective factors to emerge in this study were basing self-esteem on
      competence at school and other activities. DISCUSSION: Basing self-esteem on
      intimate relationships was associated with similar physical and health problems
      to basing self-esteem on shape and weight. The implications of these findings
      with regard to healthy adolescent development are addressed.

PMID- 12210650
TI  - An evaluation of the relationship between mood and binge eating in the natural
      environment using ecological momentary assessment.
AB  - OBJECTIVE: Although many current theories of disordered eating focus on affective
      mechanisms, relatively little is known about the covariation of mood and eating
      in peoples' natural environments. This study examined the relationship between
      mood and binge eating behavior in the natural environment. METHOD: Twenty-seven
      college students with subclinical binge eating behavior self-monitored their mood
      on a handheld computer seven times daily for 2 weeks. RESULTS: On binge days,
      participants reported having significantly worse mood than on nonbinge days. When
      the trajectory of mood around the time of a binge was examined, no significant
      differences between prebinge and postbinge time were found when the entire binge
      day was examined. No mood differences were found between just prior to the binge
      (30-60 min prior to binge) compared with just after the binge (also within 30-60
      min). A postbinge report indicated that reported mood immediately after a binge
      was worse than mood just prior to the binge. DISCUSSION: This study provides
      evidence that the affective experience of binge eating, when assessed in the
      natural environment, is negative. Furthermore, there was no evidence that binge
      eating was a response to an immediate or transient negative mood state or that
      binge eating provided relief from negative mood.

PMID- 12210651
TI  - The situational inventory of body-image dysphoria: psychometric evidence and
      development of a short form.
AB  - OBJECTIVE: Among the facets of the multidimensional body-image construct is the
      experience of dysphoric emotions about the body in specific situational contexts.
      The present article reviews the evidence concerning a unique measure of this
      facet, the Situational Inventory of Body-Image Dysphoria (SIBID). METHOD: The
      reliability and validity of the SIBID were examined across multiple studies
      conducted by the author. Because the 48-item length of this measure may preclude
      its use by some researchers, a 20-item short-form was developed and evaluated.
      RESULTS: Findings consistently confirmed the SIBID's internal consistency,
      stability, and convergent, discriminant, and construct validity. The short form
      was found to be a psychometrically sound alternative to the longer version.
      DISCUSSION: The SIBID has utility in assessing negative body-image affect. Its
      use in research with both clinical and nonclinical populations is encouraged.

PMID- 12210652
TI  - Pattern of birth and eating attitudes in young adults: failure to replicate in a
      warmer climate.
AB  - OBJECTIVE: Previous research (based in the United Kingdom) has shown a link
      between warmer temperatures at birth and restrictive eating attitudes in early
      adulthood. The current study examined whether this pattern can be replicated in a
      warmer area of the northern hemisphere (Southwest Spain). METHODS: The
      participants were 261 preuniversity volunteers (125 women and 136 men) born in
      Extremadura, Southwest Spain. Mann-Whitney tests and chi-square analyses were
      used to compare the eating characteristics of participants born in warm versus
      cooler months. Spearman's rho was used to test for dimensional associations
      between temperature at birth and eating characteristics. RESULTS: There were no
      links between temperature at birth and restrictive eating attitudes, whether
      temperature and eating pathology were considered dimensionally or categorically.
      DISCUSSION: The association of temperature at birth and restrictive eating
      pathology in early adulthood is not replicable in a warmer climate. Possible
      explanations are suggested to account for this pattern of findings.

PMID- 12210653
TI  - Gastric dilatation in a girl with former obesity and atypical anorexia nervosa.
AB  - OBJECTIVE: This case report describes a 16 year-old girl of normal weight with
      acute gastric dilatation due to binge eating habits. METHOD AND RESULTS:
      Psychiatric assessment revealed a history of obesity and later atypical anorexia
      nervosa, but no current diagnosis of a typical eating disorder. After one month
      of daily binges a food excess was followed by an acute massive gastric dilatation
      which led to a laparotomy. DISCUSSION: Clinicians should be aware that abnormal
      eating habits may cause severe somatic complications even in patients of normal
      weight who are not currently diagnosed as having a typical eating disorder.
      Careful investigation of eating habits might have resulted in therapeutic gastric
      emptying at an earlier stage, thus avoiding the need for surgery in our patient.

PMID- 12210654
TI  - Research on energy expenditure in individuals with eating disorders: a review.
AB  - OBJECTIVE: This study reviews the published research on energy expenditure in
      individuals with anorexia nervosa (AN), bulimia nervosa (BN), and binge eating
      disorder (BED). METHOD: Individual studies are reviewed and their results
      summarized. RESULTS: The most consistent finding is a reduction in resting energy
      expenditure (REE) in patients with AN, which increases with increased energy
      intake and body weight. Data regarding BN are inconsistent. Three available
      studies in subjects with BED have not found evidence of changes in energy
      expenditure corrected for lean body mass compared with obese non-binge eaters.
      DISCUSSION: The ability to measure REE reliably and cost-effectively may aid in
      the refeeding of patients with AN in whom REE is reduced. Changes in individuals
      with BN and BED have yet to be consistently identified.

PMID- 12210655
TI  - High-caloric supplements in anorexia treatment.
AB  - OBJECTIVE: This study compares weight gain and therapy duration in two groups of
      patients with anorexia nervosa, the first receiving a normal diet aimed at
      promoting weight gain, the second receiving high-caloric supplements in addition
      to this normal diet. The study includes patients from two clinics with comparable
      psychotherapeutic treatment settings except for the substitution. METHODS: Eighty
      four patients were examined. Of these, 29 patients with substitution were
      compared with 29 patients without substitution. In addition, 13 patients without
      substitution from the first clinic were compared with 13 patients without
      substitution from the second clinic to exclude potential differences between the
      two institutions independent of the substitution. RESULTS: Substitution leads to
      more rapid weight gain, to greater weight on discharge, and to shorter therapy
      duration. Differences could be observed between patients severely or less
      severely underweight on admission and between patients with restrictive or
      bulimic anorexia. CONCLUSION: Within the framework of inpatient psychosomatic
      treatment involving a psychotherapeutic treatment setting, substitution
      facilitates weight gain.

PMID- 12210656
TI  - Olanzapine in the treatment of anorexia nervosa: an open label trial.
AB  - OBJECTIVE: The primary goal of the study was to determine if olanzapine is
      effective in producing weight gain in patients with anorexia nervosa. METHOD:
      Twenty patients with anorexia nervosa (restricting or binge/purge subtype)
      without schizophrenia, schizoaffective disorder, or bipolar disorder enrolled in
      an open label study of olanzapine 10 mg. Patients attended weekly drug monitoring
      sessions and weekly group medication adherence sessions that provided
      psychoeducation. RESULTS: Eighteen patients received the drug and 14 patients
      completed the 10-week study. The four drop-outs had gained a mean of 3.25 lb at
      their last visit. Of the 14 patients who completed the study, 10 gained an
      average of 8.75 lb and 3 of these patients attained their ideal body weight. The
      remaining four patients who completed the study lost a mean of 2.25 lb.
      DISCUSSION: These findings are promising with clinically significant weight gain
      in an outpatient setting during a brief 10-week period.

PMID- 12210657
TI  - Predictors of relapse following successful dialectical behavior therapy for binge
      eating disorder.
AB  - OBJECTIVE: To identify predictors of relapse at 6-month follow-up for women with
      binge eating disorder (BED). METHOD: Participants were 32 women with BED who had
      initially achieved abstinence from binge eating after 20 weeks of dialectical
      behavior therapy (DBT) adapted for patients with BED. Posttreatment predictor
      variables included the subscales Restraint, Weight Concerns, and Shape Concerns
      from the Eating Disorders Examination (EDE), the Emotional Eating Scale score,
      the Rosenberg Self-Esteem Scale, body mass index, and early versus late age of
      binge eating onset. RESULTS: The largest effect sizes for predicting relapse were
      found with early onset of binge eating and higher EDE Restraint scores.
      DISCUSSION: Previous findings that earlier age of onset (age 16 years or younger)
      is linked to less successful treatment outcome are now extended to the 6-month
      follow-up assessment. The finding that higher restraint scores after treatment
      predict relapse adds to the literature concerning the role of restraint in
      patients with BED.

PMID- 12210658
TI  - Bulimia nervosa: friend or foe? The pros and cons of bulimia nervosa.
AB  - OBJECTIVE: The aim of the current study was to use a qualitative approach to
      investigate the attitude of people with bulimia nervosa (BN) to their illness.
      METHOD: Patients with BN were asked to write two letters to their bulimia, one
      addressing it as a friend and the other addressing it as an enemy. We used a
      coding scheme to classify themes in letters of people with anorexia nervosa (AN)
      to group together themes expressed by those with BN. We revised the coding scheme
      to include themes that were not present in the letters of people with AN.
      RESULTS: There were both similarities and differences in the themes described by
      AN and BN patients. Two positive themes (BN allowing the individuals to eat and
      not get fat and BN as a way of dealing with boredom) and two negative themes
      (shame or low self-esteem resulting from BN and obsessive thoughts of weight and
      shape) were added to the coding scheme to account for these differences.
      DISCUSSION: The positive and negative aspects of BN differ in some important ways
      from those expressed by patients with AN. The meaning of these differences is
      discussed with reference to the wider symptom pattern of BN compared with AN and
      their importance with reference to motivation for change is outlined.

PMID- 12210659
TI  - Alcohol and drug-related negative consequences in college students with bulimia
      nervosa and binge eating disorder.
AB  - OBJECTIVE: The purpose of this study was to investigate the association between
      disordered eating and substance use in a nonclinical sample of college students.
      METHOD: Participants completed the Eating Disorder Diagnostic Scale (EDDS), which
      includes full diagnostic criteria for bulimia nervosa (BN), binge eating disorder
      (BED), and anorexia nervosa (AN) as outlined in the 4th edition of the Diagnostic
      and Statistical Manual of Mental Disorders, as well as assessments of both
      alcohol and drug use and use-related consequences. RESULTS: Individuals meeting
      criteria for BN reported more alcohol-related negative consequences despite the
      fact that they did not drink significantly more alcohol and did not drink more
      frequently than non-eating-disordered individuals. Similarly, individuals with BN
      reported more negative consequences related to illicit drug use than non-eating
      disordered individuals, although no differences in lifetime and recent use of
      drugs were found. DISCUSSION: Results highlight the importance of distinguishing
      between use and consequences in evaluating eating disorders and comorbid
      substance use problems.

PMID- 12210660
TI  - Relationship among body image, exercise behavior, and exercise dependence
      symptoms.
AB  - OBJECTIVE: The purpose of the present study was to examine the relationship among
      body image, exercise behavior, body mass index (BMI), and primary exercise
      dependence symptoms in physically active individuals. METHOD: Male and female
      university students (N = 474) completed self-report measures of exercise
      behavior, height, weight, exercise dependence symptoms, social physique anxiety,
      and body satisfaction. RESULTS: Hierarchical multiple regressions with forced
      block entry by gender were conducted to examine the effects of exercise behavior,
      BMI, and exercise dependence symptoms on body satisfaction and social physique
      anxiety. For females, BMI was the strongest positive predictor of body
      dissatisfaction and social physique anxiety. For males, exercise behavior was the
      strongest negative predictor of body dissatisfaction and social physique anxiety.
      DISCUSSION: It was concluded that after controlling for the effects of BMI and
      exercise behavior, primary exercise dependence symptoms were not strong
      predictors on body image, especially for females.

PMID- 12210661
TI  - Reported sexual abuse and bulimic psychopathology among nonclinical women: the
      mediating role of shame.
AB  - OBJECTIVE: Despite consistent evidence that a reported history of sexual abuse is
      linked to later bulimic psychopathology, less is known about the psychological
      processes that underpin this relationship. This study examines the hypothesis
      that shame acts as a mediator in the link between reported sexual abuse and
      bulimic attitudes. METHOD: A nonclinical sample of female undergraduates (N =
      214) completed standardized measures of experiences of sexual abuse, internalized
      shame, and bulimic psychopathology. Regression analyses were used to test for the
      mediating role of shame. RESULTS: The findings were compatible with a model where
      levels of shame partially account for the relationship between any history of
      reported sexual abuse and bulimic psychopathology, but entirely account for the
      link between intrafamilial abuse and bulimic attitudes. CONCLUSIONS: The
      experience of shame appears to be important in understanding the relationship
      between reported sexual abuse and bulimic attitudes. Where individuals report a
      history of sexual abuse, particularly intrafamilial abuse, it may be clinically
      useful to focus on shame as a psychological consequence of that experience.

PMID- 12210662
TI  - A large-scale survey of eating disorder symptomatology among female adolescents
      in the People's Republic of China.
AB  - OBJECTIVES: This study was designed to document comprehensively the prevalence of
      the signs, symptoms, and associated features of anorexia nervosa and bulimia
      nervosa among schoolgirls in the People's Republic of China. METHODS: Female
      participants were recruited from both junior and senior high schools with varying
      levels of academic performance in six cities (Beijing, Shanghai, Guangzhou,
      Zunyi, Xin Xiang, and Yinchuan) that are representative of different geographical
      regions in China (North East, Central East, South East, South West, North West,
      and North). In each school, girls were recruited across all grades, in order to
      cover ages 12-19 years. The final sample comprised 1,246 participants whose mean
      age was 15.76 years. The questionnaire, developed specifically for the purpose of
      this research, assessed the diagnostic criteria and associated features of
      anorexia nervosa and bulimia nervosa outlined in the 4th ed. of the Diagnostic
      and Statistical Manual of Mental Disorders. RESULTS AND DISCUSSION: Our results
      have shown a surprisingly high level of weight-related concerns among schoolgirls
      across mainland China. There would seem to be few cases of anorexia or bulimia,
      although some girls satisfy criteria for partial diagnoses. Our findings
      highlight the difficulty of identifying girls who are underweight, at least by
      applying the standard Western procedure for categorizing body mass index.

PMID- 12210663
TI  - Characteristics of eating disorder patients without a drive for thinness.
AB  - OBJECTIVE: The aim of this study was to investigate two samples of patients
      affected by anorexia nervosa (AN) or bulimia nervosa (BN), respectively, with and
      without the diagnostic feature of drive for thinness (DT). METHOD: The samples
      comprised 70 consecutive eating disorder (ED) outpatients at the Department of
      Psychiatry (University of Pisa) and 106 AN patients admitted to a day hospital in
      Toronto, Canada. Subjects were assessed on clinical and psychometric parameters.
      RESULTS: In both countries, 17% of the subjects had low DT as measured by the
      Eating Disorder Inventory (EDI). They comprised the atypical group and appeared
      to have less severe psychopathology. DISCUSSION: Weight phobia should not be
      viewed as critical to the diagnosis of ED and DT could be a culture-bound
      dimension. Considering the differences between the two groups, the
      characterization of patients as typical and atypical may be clinically useful.

PMID- 12210664
TI  - Fear, disgust, and abnormal eating attitudes: a preliminary study.
AB  - OBJECTIVE: Clinical descriptions of eating disorders emphasize the role of fear
      (e.g., fear of weight gain, weight phobia, morbid dread of fatness). The present
      study explored whether disgust, an emotion that is linked intimately with food,
      may also be an important emotional response to eating and weight-related issues
      in women with abnormal eating attitudes. METHOD: Forty nonclinical female
      participants were presented with a series of food, drink, body shape, and emotion
      related stimuli. They were asked to rate each on a number of responses associated
      with fear and disgust. In addition, participants completed standard questionnaire
      measures of eating attitudes, phobias, and disgust sensitivity. RESULTS: Ratings
      of fear and disgust were higher in women with abnormal eating attitudes than in
      those without for high-calorie foods and for overweight body shapes, but not for
      drinks and slim body shapes. In response to fear and disgust relevant images,
      women with abnormal eating attitudes also rated emotional responses higher, but
      this was restricted to the appropriate emotion (i.e., higher levels of fear in
      response to fear stimuli and higher levels of disgust in response to disgust
      stimuli). CONCLUSION: In women with abnormal eating attitudes, both disgust and
      fear responses to food and body shape issues are equally salient. Thus, an
      emphasis on fear in eating disorders, to the exclusion of disgust, may be
      unwarranted.

PMID- 12210665
TI  - The impact of racial stereotypes on eating disorder recognition.
AB  - OBJECTIVE: Eating disorders are commonly believed to affect Caucasian women more
      so than other women. The authors examined whether participants recognize
      disturbed eating symptoms to a lesser degree in an African American or Hispanic
      female compared with a Caucasian female. METHOD: A sample of 160 undergraduate
      students of different ethnic backgrounds read a passage about an adolescent girl
      who displayed eating disorder symptoms. Participants received one of three
      passages; the passages differed only regarding the girl's race (African American,
      Caucasian, or Hispanic). Participants completed questionnaires used to reveal
      possible racial stereotypes about eating disorders. RESULTS: The study found that
      the race of the adolescent girl had a significant impact on detection of
      disturbed eating patterns, such that participants recognized the eating disorder
      more when they read about a Caucasian girl than when they read about a minority
      girl (Hispanic or African American). DISCUSSION: The results have implications
      for public awareness of eating disorders, as well as clinical implications for
      work with eating disorder patients from various ethnic backgrounds.

PMID- 12210666
TI  - Eating-related concerns, mood, and personality traits in recovered bulimia
      nervosa subjects: a replication study.
AB  - OBJECTIVE: Limited data suggest that eating-related concerns and behaviors,
      disturbances in mood, and altered temperament persist following recovery from
      bulimia nervosa (BN). METHOD: In order to replicate and extend such findings, 11
      women who were long-term recovered from BN (>1 year with no binging, purging, or
      restricting behaviors, normal weight, and regular menstrual cycles) were compared
      with 15 healthy volunteer women on the Eating Disorders Invertory-2 (EDI-2), the
      Beck Depression Inventory, the State Trait Anxiety Inventory, and the
      Multidimensional Personality Questionnaire (MPQ). RESULTS: Compared with the
      control women, the recovered BN women showed elevated levels of the EDI-2
      subscales of Drive for Thinness, Body Dissatisfaction, Ineffectiveness,
      Perfectionism, and Social Insecurity, greater depression and anxiety, elevated
      levels of the MPQ Stress Reaction dimension and the higher-order factor of
      Negative Emotionality, and lower levels of the MPQ Well Being and Closeness
      dimensions. DISCUSSION: Core eating and weight-related concerns, dysphoric
      affect, social discomfort, and personality traits indicative of perfectionism
      persist following long-term recovery from BN.

PMID- 12210667
TI  - The effects of psychoeducation on disturbed eating attitudes and behavior in
      young women with type 1 diabetes mellitus.
AB  - OBJECTIVE: This study aimed to evaluate the effect of a six-session
      psychoeducation (PE) program on young women with type 1 diabetes mellitus (DM)
      and disordered eating attitudes and behavior. METHOD: Two hundred twelve young
      women attending a pediatric diabetes clinic were screened for signs of eating
      disturbance. Of these women, 130 passed the screening and were invited to
      participate in the intervention phase of the study. Eighty-five subjects were
      randomized to the PE or treatment-as-usual group. Assessments were conducted
      before and after treatment and at 6-month follow-up. RESULTS: Intention-to-treat
      group by time multivariate analyses of variance (MANOVAs) indicated significant
      reductions following PE treatment on the Restraint and Eating Concern subscales
      of the Eating Disorder Examination (EDE) and on the Drive for Thinness and Body
      Dissatisfaction subscales of the Eating Disorder Inventory (EDI), but no
      improvement in frequency of purging by insulin omission or hemoglobin A1c levels.
      DISCUSSION: The PE group was associated with reductions in eating disturbance,
      but not with improved metabolic control.

PMID- 12210668
TI  - Hypophosphatemia following self-treatment for anorexia nervosa.
AB  - Hypophosphatemia is recognized as a serious complication of hospital treatment
      for patients with anorexia nervosa but may also occur prior to medical
      intervention. METHOD: This paper reports a case of severe hypophosphatemia in a
      patient who consumed large quantities of carbohydrates following a period of
      dietary restraint. DISCUSSION: The possible mechanisms underlying the
      hypophosphatemia in this case are discussed and its management is described.

PMID- 12210669
TI  - Social system of the Alaotran gentle lemur (Hapalemur griseus alaotrensis):
      genetic characterization of group composition and mating system.
AB  - Group composition and mating system were investigated in wild Alaotran gentle
      lemurs (Hapalemur griseus alaotrensis) using genetic markers. These small-bodied
      herbivorous and cathemeral primates are endemic to the reed and papyrus beds
      around Lac Alaotra in Madagascar. They live in small groups in small, defended
      territories. Data were collected during the rainy seasons in 1996, 1997, and
      1999, and include 99 individuals from 22 neighboring social groups and an
      additional 30 animals from other areas representing most of the geographic range.
      Animals were located by researchers canoeing in the marshes bordering the lake.
      After a group's size was determined by direct observation, all individuals were
      captured, marked, and released. During handling each individual was weighed and
      sexed, and hair samples for DNA extraction were collected. A 342 bp mtDNA control
      region sequence and 10 nuclear microsatellite loci provided multilocus genotypes
      that were used to assess pedigree relations and population structure. Alaotran
      gentle lemurs were found in groups of two to nine individuals (mean: 4.3),
      comprising one or two breeding females, their offspring, and one reproducing
      male. Solitary individuals of both sexes were encountered rarely. Breeding
      females were the permanent core of the social groups, whereas intergroup transfer
      of reproductive males was relatively frequent. Forty percent of all reproducing
      groups contained two breeding females, which were related to each other as
      closely as mother-daughter or full sisters. Parentage assessment revealed a
      variable mating system ranging from serial monogamy to polygyny within social
      groups. At least 8% of paternities involved extragroup males. Additional data on
      life history and reproduction are presented, and the social system of the
      Alaotran gentle lemur is discussed in the light of the new genetic findings.

PMID- 12210670
TI  - Chromosomal homologies between Cebus and Ateles (primates) based on ZOO-FISH and
      G-banding comparisons.
AB  - ZOO-FISH (Fluorescent "in vitro" hybridization) was used to establish the
      chromosomal homology between humans (HSA) and Cebus nigrivitatus (CNI) and Ateles
      belzebuth hybridus (ABH). These two species belong to different New World monkey
      families (Cebidae and Atelidae, respectively) which differ greatly in chromosome
      number and in chromosome morphology. The molecular results were followed by a
      detailed banding analysis. The ancestral karyotype of Cebus was then determined
      by a comparison of in situ hybridization results, as well as chromosomal
      morphology and banding in other Platyrrhini species. The karyotypes of the four
      species belonging to the genus Cebus differ from each other by three inversions
      and one fusion as well as in the location and amounts of heterochromatin. Results
      obtained by ZOO-FISH in ABH are in general agreement with previous gene-mapping
      and in situ hybridization data in Ateles, which show that spider monkeys have
      highly derived genomes. The chromosomal rearrangements detected between HSA and
      ABH on a band-to-band basis were 27 fusions/fissions, 12 centromeric shifts, and
      six pericentric inversions. The ancestral karyotype of Cebus was then compared
      with that of Ateles. The rearrangements detected were 20 fusions/fissions, nine
      centromeric shifts, and five inversions. Atelidae species are linked by a
      fragmentation of chromosome 4 into three segments forming an association of 4/15,
      while Ateles species are linked by 13 derived associations. The results also
      helped clarify the content of the ancestral platyrrhine karyotype and the mode of
      chromosomal evolution in these primates. In particular, associations 2/16 and 5/7
      should be included in the ancestral karyotype of New World monkeys.

PMID- 12210671
TI  - Contexts and behavioral correlates of trill vocalizations in wild white-faced
      capuchin monkeys (Cebus capucinus).
AB  - Primate vocalizations that appear to occur independently of specific contexts
      typically are considered to be contact calls. However, results from several
      recent studies indicate that these calls function to facilitate social
      interactions. White-faced capuchin monkeys (Cebus capucinus) emit a high
      frequency vocalization, termed a "trill," in social interactions and during
      travel. In this study, immatures emitted most trills, but adult females also
      trilled; by contrast, adult males rarely trilled. Infants emitted the majority of
      trills, and they trilled at significantly higher rates than adult females.
      Infants trilled most when approaching other individuals. Furthermore, infants
      emitted proportionately more trills than other age classes when approaching other
      individuals. I therefore focused on the detailed context and immediate behavioral
      correlates of trilling by infants. Infants that trilled when approaching others
      tended to interact affiliatively with them subsequently (i.e., climbing on,
      touching, receiving grooming, and performing food inspection) more than infants
      that did not trill when approaching. Therefore, infant trilling may have had an
      immediate effect on the recipient's behavior.

PMID- 12210672
TI  - Sequential culture medium promotes the in vitro development of Macaca
      fascicularis embryos to blastocysts.
AB  - In vitro production of blastocyst stage embryos from Macaca fascicularis (Mf) has
      not previously been demonstrated without cell support. Historical data indicates
      that a large proportion of Mf embryos arrest at the morula stage in nonsequential
      culture medium (NSM) lacking serum supplementation and/or cell support. Here we
      report the application of a sequential culture system supporting in vitro
      production of Mf blastocysts. Mf embryos produced by in vitro fertilization (IVF;
      n = 69) were subjected to in vitro culture without cell support in either a
      commercial sequential embryo culture medium (SM) or an NSM. At 24 hr post
      insemination (PI) embryos generated from in vivo and in vitro matured oocytes and
      cultured in the NSM cleaved to two or more cells in significantly greater
      proportions (15/23; 65%) compared to embryos cultured in SM (14/46; 30%).
      However, by day 3 PI embryo development beyond eight cells was not different in
      NSM (9/23; 39%) compared to SM (25/46; 54%). At day 5 PI embryo development to
      the morula stage was slightly lower in NSM (8/23, 35%) compared to SM (21/46,
      45%), and embryo degeneration was slightly higher in NSM (9/23, 39%) compared to
      SM (9/46, 20%). After 7-9 days of in vitro culture, embryo development to the
      blastocyst stage and embryo degeneration were significantly lower and higher,
      respectively, in NSM (0/23, 0%; and 23/23, 100%) compared to SM (9/46, 20%; and
      26/46, 56%). In this study the sequential culture system was better able to
      support in vitro development of Mf embryos compared to nonsequential culture
      systems.

PMID- 12210673
TI  - Response patterns of bonnet macaques following up to 75 weeks of continuous
      access to social-video and food rewards.
AB  - Three individually housed bonnet macaque males were given 75 weeks of continuous
      access to a joystick task with a reward choice of either viewing live color video
      of a bonnet group or obtaining a banana-flavored food treat. Here we report data
      for weeks 44-75 following a change in the stimulus group displayed in the video.
      The new stimulus group enhanced responding to the video for two subjects over the
      entire 32 weeks of this study, although there was some decline across weeks, and
      the video continued to be an effective reward for the duration of the study for
      all subjects.

PMID- 12210674
TI  - Disappearances of individuals from social groups have implications for
      understanding natal dispersal in monogamous owl monkeys (Aotus azarai).
AB  - The socially monogamous owl monkeys (Aotus spp.) live in small groups of two to
      five individuals. We used monthly demographic data collected from 16 social
      groups between 1997-2001 to estimate the age of disappearance from their natal
      groups and the timing of those disappearances in a population of owl monkeys
      (Aotus azarai azarai) in Formosa, Argentina. We applied survival analysis
      techniques to 48 months of observations of 47 individuals to construct age
      specific probabilities of disappearance. Two-thirds of the individuals (eight of
      12), for which disappearance could be well timed, disappeared at around 2 years
      of age. The average age at disappearance for these individuals was 29 months (+/
      8), whereas the mean age of disappearance obtained from the survival analysis of
      censored and uncensored data was almost 3 years (mean+/-SD, 35+/-3 months).
      Ninety-two percent of all disappearances of adult size individuals (11 of 12)
      occurred around the birth season. Our data suggest that at least some individuals
      disperse soon after sexual maturation while others remain for up to 4 years in
      their natal groups.

PMID- 12210675
TI  - Agricultural Safety and Health in a New Century. Proceedings of a conference. 28
      30 April 2000, Cooperstown, New York, USA.
AB  - BACKGROUND: The National Institute of Occupational Safety and Health Agricultural
      Centers periodically convene center scientists and educators working on NIOSH
      sponsored projects and other persons with expertise in agricultural safety and
      health. METHODS: Selected papers from the most recent conference in April, 2000,
      are presented. They focus on ergonomic factors, hazards to the health and safety
      of migrant workers and educational efforts in this population, injuries to
      children, the environmental hazards of discarded agrichemicals, the difficulty of
      assessing worker exposure, non-Hodgkin's lymphoma in Canadian farmers,
      prioritization of health and safety issues and the economics of roll-over
      protective structures. CONCLUSIONS: The diversity and severity of the challenges
      in agriculture both on small farms and in agribusiness are enormous. It is hoped
      that these papers will assist professionals at all levels in addressing these
      complex problems.

PMID- 12210676
TI  - Ergonomic exposures in apple harvesting: preliminary observations.
AB  - BACKGROUND: Recent research on occupational injury to apple harvest workers in
      New York and Pennsylvania indicates that muscle strain is one of their leading
      problems. A descriptive study of ergonomic risks for strains of the shoulder and
      lower back among apple harvesters was carried out to identify opportunities for
      intervention. METHODS: Based upon pilot observation in four orchards, a Posture
      Activities-Tools-Handling (PATH) data collection template was designed and used
      to analyze the work of fifty-one workers in eight additional apple orchards.
      RESULTS: Physical loading on the shoulder appears to result from three major
      factors: reaching to pick apples with elbows over shoulder height; downward
      pressure from the bucket's strap in contact with the collarbone; and strain from
      carrying the ladder. Strain to the back appeared to come from three
      circumstances: static, awkward picking postures; bending to empty the picking
      bucket into the bin; and supporting a full load of the apples with the lower
      back. CONCLUSION: Possible intervention strategies are suggested, with emphasis
      on direct communication and active involvement on the part of the growers and
      harvesters.

PMID- 12210677
TI  - Ergonomic exposure case studies in Massachusetts fishing vessels.
AB  - BACKGROUND: Musculoskeletal disorders may not have been studied as much as
      greater risks in the dangerous environment of commercial fishing. Primary
      prevention of risk for these kinds of injuries and illnesses begins by a detailed
      understanding of what risks are likely to be common in the different fisheries,
      and how those risks might be reduced. METHODS: Ergonomic job analyses were
      conducted on three different types of fishing vessels in Massachusetts:
      gillnetting, otter trawling, and lobstering. Direct observation was used to link
      posture to task. Noise measurements, tool analysis, and cycle time measurements
      were also included. RESULTS: Production speed, materials handling, and vessel
      movement contributed to musculoskeletal stress by affecting observable postural
      deviation, repetition, and forceful exertions. CONCLUSIONS: Interventions to
      reduce ergonomic risk factors might be possible through utilization of below deck
      space in certain boats, through better technology, or through simple tool
      adjustments.

PMID- 12210678
TI  - Assessment of occupational health and safety risks of farmworkers in Colorado.
AB  - BACKGROUND: Migrant farmworkers face a variety of hazards including exposure to
      pesticides and agricultural chemicals. However, few studies have quantatively
      evaluated these risks. METHODS: Hazards were assessed during 32 field surveys
      conducted in the agricultural fields and 15 surveys at five camps. Observations
      of 1,461 farmworkers for potential hazards were recorded. Estimated risk was
      evaluated on a four-point scale (no hazard, minor, serious, and critical). A
      total of 229 farmworkers were interviewed about field conditions. RESULTS: Two
      out of the five camps did not have safe drinking water. Risks for farmworkers
      were lower when a manager was living on site. Field surveys estimated higher risk
      when provision of sanitation was deficient (P < 0.05). Farmworkers' responses
      concerning field conditions differed from the survey findings. CONCLUSIONS: Risks
      for farmworkers depended largely on the environment provided. Discordances
      between survey results and farmworkers' interview responses suggested that self
      reported data might have limited validity for this population. Working and living
      conditions require improvement to decrease occupational risks for farmworkers.

PMID- 12210679
TI  - Theater as a mechanism for increasing farm health and safety knowledge.
AB  - BACKGROUND: The agricultural industry has one of the highest injury and fatality
      rates of all industries in the US. Hispanic farm workers constitute the largest
      percentage of farm workers on Eastern Washington farms. Literacy levels, language
      skills, and migration patterns need to be considered when developing farm health
      and safety education. Theater was chosen as a method to provide health education
      and farm safety training to farm workers and their families living in a three
      county region of Eastern Washington. METHODS: The most urgent health and safety
      education needs of Hispanic farm workers were identified by a series of focus
      groups and key informant interviews. The resulting data was used to develop four
      Spanish one-act plays, which were presented in each of the three counties. To
      test the effectiveness of theater as an educational tool each of the plays was
      accompanied by pre-and post-play self-report questionnaires. These were analyzed
      using two-tailed Chi-square (chi(2)) tests of significance and a one-tail
      Marginal Homogeneity statistic. RESULTS: A total of 301 persons completed pre
      test post-test questionnaires; 185 were farm workers and 115 were local community
      members. Thirteen of seventeen questions designed to measure information gained
      directly from the plays showed a significant degree of positive knowledge change
      (P = < 0.10). Follow-up interviews conducted 2 months after play viewing suggest
      that participants retain some of the health and safety messages in the plays.
      CONCLUSIONS: The hypothesis, "appropriate farm health and safety knowledge
      increases as a result of attendance at a one-act Spanish play enacted by a
      community players' group" was validated since 13 of 17 questions showed a
      significant degree of positive knowledge change. Overall, participants indicated
      that they liked the plays, recalled the story lines easily, and would attend
      additional plays if given the opportunity.

PMID- 12210680
TI  - New York State child agricultural injuries: how often is maturity a potential
      contributing factor?
AB  - BACKGROUND: Children living or working on New York farms face unique hazards and
      experience on-farm injuries related to these. The New York Community Partners for
      Healthy Farming (CPHF) surveillance provided a unique source of information for
      analyses of risk factors-particularly age-for these events. METHODS: Agricultural
      injuries recorded by the state's agricultural nurse surveillance (CPHF) program
      over a 6-year period were analyzed. Injuries were classified by type, severity,
      and possible contributing factors, including whether the age of the victim was
      below the "job appropriate age limits" designated by the investigators using
      materials from the North American Guidelines for Children's Agricultural Tasks
      (NAGCAT). RESULTS: Of the 164 recorded injuries to persons aged 1-18 years, 29
      were fatalities, 18 were disabling, and 55% occurred while working. Leading
      injury types were tractor run-over (12) and overturns (11). Of those injured
      while working, 35% were under the "job appropriate age limits." Tasks of loading
      hay (square bales) (100%, 3), fieldwork with trailed implements (100%, 3), and
      feeding calves (100%, 2) most frequently involved very young victims. Grouped by
      injury source, injuries involving non-powered wagons had the highest frequency of
      under-age victims (82%, 9). CONCLUSION: The frequency of problems with job
      appropriate ages suggests that some children on NY farms may be developmentally
      inappropriate for the tasks to which they are being assigned. The NAGCAT
      Guidelines are a needed tool for child agricultural injury prevention in New
      York.

PMID- 12210681
TI  - Reclamation of pesticides in New York State.
AB  - BACKGROUND: Unwanted agrichemicals pose a unique threat that many states now
      address this with statewide collection programs. In New York, this is done at the
      discretion of individual counties. METHODS: We compiled and analyzed registration
      inventories from five separate county-based pesticide collections located in
      three different agricultural regions. Telephone surveys of thirty-one of New
      York's leading agricultural counties gathered information on their strategies for
      disposal of unwanted pesticides. RESULTS: The combined collections yielded 54,214
      pounds of pesticides from 123 farms (441 lbs/farm). The most common active
      ingredients collected included older (and often discontinued) agents such as
      organochlorine (5,355 lbs, 9.8%) and arsenic (3,832 lbs, 7.1%) compounds, as well
      as more modern and commonly used active ingredients such as organophosphate
      pesticides (3,200 lbs, 5.9%). Disposal costs ranged from $2.03 to $2.86 per
      pound. Data from three collections indicated that 27% of the recovered pesticide
      (13,123 lbs) was stored in "unacceptable", "leaky", or "poor" containers. Of 31
      agricultural counties, only 17 (55%) have hosted at least one farm pesticide
      collection event in the past. Planning for future collections is quite limited.
      CONCLUSIONS: There is a potentially large amount of toxic chemicals, some in
      decaying containers, that poses a risk to soil and groundwater in the state. The
      planning of future collections in New York State is haphazard. Carefully designed
      pesticide collection projects can be effective and should be a priority for local
      and state health officials.

PMID- 12210682
TI  - Cholinesterase measurements with an automated kit.
AB  - BACKGROUND: The Test-mate kit determines acetylcholinesterase (AChE, EC 3.1.1.7)
      and hemoglobin content of a drop of blood, displaying enzyme activities
      normalized to 25 degrees C. Previous models produced inconsistent results at
      different temperatures. This report focuses on the current model, ChE 400, and
      two instruments of a previous OP model. METHODS: AChE activities were determined
      by the Ellman assay, using the three kits and a 96-well microplate reader.
      Temperatures ranged from 10 to 37 degrees C. Fetal bovine serum was the source of
      AChE. RESULTS: Normalized activities decreased below 20 degrees C in the ChE
      model and below 25 degrees C in the OP models. Activities of the same serum
      sample differed between the three Test-mate kits, ranging from 1.03 to 1.49
      micromoles/min/ml. Percent errors were greater than with the microplate reader at
      all temperatures. CONCLUSIONS: Neither we nor the manufacturer recommend the
      current Test-mate model for fieldwork. Nevertheless, there have been field
      measurements with Test-Mate kits, and we recommend that an enzyme activity
      standard be run in parallel with their use.

PMID- 12210683
TI  - Canadian male farm residents, pesticide safety handling practices, exposure to
      animals and non-Hodgkin's lymphoma (NHL).
AB  - BACKGROUND: A majority of published studies indicate that farmers have an
      elevated risk of developing non-Hodgkin's lymphoma (NHL) compared to other
      workers. METHODS: We evaluated accidental exposure to pesticides, the use of
      personal protective equipment, and exposure to animals among male farm residents
      in a Canadian population-based, multi-centre, NHL-control questionnaire study.
      RESULTS: In a multivariate model, the following variables had statistically
      significant adjusted odds ratios (OR) using 95% confidence intervals (95% CI) (a)
      higher risk: having more than 13 head of swine, raising bison, elk or ostriches,
      a personal history of cancer, > 4 and < or = 15 years of farm residence and
      occupational exposure to diesel fuel and exhaust; (b) lower risk: raising cattle
      and a personal history of measles. CONCLUSIONS: Future multidisciplinary studies
      of NHL should include a comprehensive review of exposure to animals in sufficient
      detail to assess etiological mechanisms to explain the putative associations
      between exposure to farm animals and NHL.

PMID- 12210684
TI  - Health and safety hazards in Northwest agriculture: setting an occupational
      research agenda.
AB  - BACKGROUND: Agriculture is among the most hazardous occupations in the United
      States. Research can provide new insights about disease and injury and serve as
      the foundation for occupational health and safety policies. The determination of
      research priorities can be problematic. Public participation approaches offer
      opportunities to identify and integrate various perspectives. METHODS: The agenda
      process was modeled on the NIOSH National Occupational Research Agenda. Center
      staff contacted representatives of producer groups, labor, health care, academia,
      and public agencies to participate in telephone interviews and a daylong
      workshop. RESULTS: Twelve research priorities were identified: musculoskeletal
      disorders; respiratory disease; skin disease; traumatic injuries; chemical
      exposures; special populations at risk; social and economic foundations of
      workplace safety; risk communication barriers; diagnostic approaches; hazard
      control technology; intervention effectiveness; and surveillance research
      methods. CONCLUSIONS: The agenda process engaged stakeholders in priority
      setting. The resulting document is a useful guide for occupational safety and
      health in agriculture.

PMID- 12210685
TI  - Cost-effectiveness of roll-over protective structures.
AB  - BACKGROUND: Roll-over protective structures (ROPS) are proven to prevent
      fatalities from agricultural tractor overturns, accounting for more than one
      third of all production agriculture-related fatalities in the United States. In
      1997, there were approximately 1.2 million ROPS-retrofittable tractors in the
      United States. METHODS: A decision analysis is used to compare the health
      outcomes of installing ROPS on retrofittable tractors, relative to doing nothing.
      A cost-effectiveness analysis builds on these results to assess the costs and
      benefits of installing ROPS on retrofittable tractors. RESULTS: Doing nothing
      would result in 1,450 fatalities and 1,806 nonfatal injuries, while installing
      ROPS would prevent 1,176 fatalities and 957 nonfatal injuries. Installing ROPS
      would cost $489,373 per injury prevented. CONCLUSIONS: Installing ROPS on
      retrofittable tractors would reduce fatalities from tractor overturns by more
      than 80% and nonfatal injuries by about 53%. The cost per injury prevented would
      be similar to that of other injury-preventing interventions. ROPS would help
      prevent additional injuries from falling off tractors and tractor collisions with
      motor vehicles.

PMID- 12210686
TI  - Induction of ferritin and lipid peroxidation by coal samples with different
      prevalence of coal workers' pneumoconiosis: role of iron in the coals.
AB  - BACKGROUND: Differences in levels of bioavailable iron (BAI) in coal may be
      responsible for the observed regional differences in the prevalence and severity
      of coal workers' pneumoconiosis (CWP). METHODS: Twenty-nine coal samples from
      three coal mine regions were tested in human lung epithelial Type II A549 cells.
      They were from Utah (UT), West Virginia (WV), and Pennsylvania (PA) with a
      prevalence of CWP of 4, 10, and 26%, respectively. RESULTS: Low molecular weight
      (LMW) chelators bound iron, a fraction of BAI in the cells released from coals,
      ferritin, and lipid peroxidation were significantly higher in cells treated with
      various coals than in control cells, with an increasing order of UT < WV < PA, in
      parallel to the prevalence of CWP in these coal mine regions. Deferoxamine (DFO),
      a specific iron chelator, was used to distinguish effects of BAI from those of
      other transition metals. Our results indicate that BAI in the coals of WV and UT
      is the main metal species in inducing ferritin and lipid peroxidation. In
      contrast, biological effects of PA coals are not only from BAI, but from other
      transition metals as well. CONCLUSIONS: Based on a large number of coal samples
      from various seams, the findings of this study provide further evidence that
      metals, particularly iron, play important roles in coal dust-induced cellular
      damage, ultimately leading to the development of CWP and contributing to the
      regional differences in the prevalence of the disease.

PMID- 12210687
TI  - Arsenic and porphyrins.
AB  - BACKGROUND: To evaluate the possible effect of inorganic arsenic (iAs) and of its
      species on the urinary excretion of porphyrin homologues. METHODS: Total
      porphyrins and their homologues (copro, penta, hexa, hepta, uroporphyrins) and
      arsenic species (trivalent and pentavalent As; monomethyl arsonic acid; dimethyl
      arsenic acid; arsenobetaine) were measured respectively by HPLC and HPLC-ICP MS
      in urine from 86 art glass workers exposed to iAs and from 54 controls. RESULTS:
      A significant increase in the excretion of penta and uroporphyrins was
      demonstrated for workers exposed to As; As3 was the species best correlated with
      urinary porphyrin excretion. CONCLUSIONS: The increase of urinary excretion for
      some porphyrin homologues appears to be consistent with the inhibition by As of
      URO-decarboxylase in the heme biosynthesis pathway. The determination of urinary
      porphyrin homologues could be useful to assess, on a group basis, some early
      effects of arsenic and to demonstrate possible individual susceptibility to the
      element.

PMID- 12210688
TI  - Estimation of the incidence of pleural mesothelioma according to death
      certificates in France.
AB  - BACKGROUND: The number of cases of pleural mesothelioma in France has varied
      substantially according to methods of assessment. MATERIALS AND METHODS: We
      collected information from certifying physicians about 316 subjects who died
      between 1 July 1992 and 30 June 1993 in three regions of France with a cause of
      death coded as ICD-9 category 163. The ICD codes selected as the cause of death
      for 178 deaths between 1 January 1987 and 31 December 1992 histologically
      confirmed and diagnosed as pleural mesothelioma by an expert committee were
      examined. Finally, we used this information to estimate the number of deaths from
      pleural mesothelioma in France in 1992. RESULTS: In Part I, 45% (men: 54%; women:
      28%) of the cases coded as ICD-9 section 163 were definitely or probably
      mesothelioma; 18% (men: 16%; women: 21%) possibly mesothelioma; and 37% (men:
      30%; women: 51%) other tumors, primarily adenocarcinoma metastases. In Part II,
      74% of the confirmed pleural mesotheliomas were coded in category 163 (men: 75%;
      women: 70%). Extrapolation nationwide indicated that 902 deaths were coded as ICD
      9 163 in 1992: 521 cases involved definite or probable mesothelioma and 724
      definite, probable, and possible cases. CONCLUSIONS: The analysis of this sample
      suggests that estimating the number of mesothelioma cases from the cause-of-death
      statistics may overestimate their incidence, but that death certificates appeared
      to report the diagnosis of histologically confirmed mesothelioma accurately.

PMID- 12210689
TI  - Occupational exposures and the risk of ovarian cancer in Sweden.
AB  - BACKGROUND: Studies of occupational exposures and ovarian cancer, often limited
      by few subjects or proportionate mortality data, have yielded inconsistent
      results. METHODS: Swedish women employed in 1960, 1970, or during both years were
      followed from 1971 to 1989 using census data linked to nationwide cancer and
      death registries. A total of 9,591 ovarian cancer cases were identified among
      1,670,517 women. Poisson regression was used to estimate the relative risk of
      ovarian cancer in specific occupational groups and in women exposed to particular
      occupational exposures defined by job exposure matrices. We lacked data on
      reproductive factors. RESULTS: Jobs associated with elevated ovarian cancer rates
      in this and previous studies include dry cleaning, telegraph and telephone work,
      paper packaging, and graphic and printing work. In contrast to results of some
      previous studies, we found that hairdressers and beauticians were not at
      increased risk of ovarian cancer. Organic dusts, aromatic amines, aliphatic and
      aromatic hydrocarbons are suggested as specific etiologic agents. CONCLUSIONS: In
      this large study, we have confirmed some results from smaller studies and
      identified some new relationships that need to be confirmed elsewhere.

PMID- 12210691
TI  - Historical risks of tuberculin skin test conversion among non-physician staff at
      a large urban hospital.
AB  - BACKGROUND: Nosocomial transmission of Mycobacterium tuberculosis among workers
      at a 1000-bed inner-city hospital led to an extensive evaluation of this risk
      among workers with potential exposure to TB patients or laboratory specimens.
      METHODS: Retrospective cohort study to determine the incidence and risk of
      tuberculin skin test (TST) conversions among workers employed 1/1/90 to 9/30/92.
      RESULTS: Personal, community, and occupational risk factors were evaluated in
      2,362 workers with potential M. tuberculosis exposure and 886 workers with no
      known exposure. The 33-month cumulative rate of TST conversion was 5.8% for
      potentially exposed workers and 2.0% for controls (RR 3.6; 95% CI; 2.2-5.8).
      Among workers with potential M. tuberculosis exposure, statistically
      significantly elevated risks were found for nurses, laboratory technicians,
      pharmacy workers, phlebotomists, housekeepers, clerks, emergency room workers,
      and emergency responders. CONCLUSIONS: Workers with patient contact and those
      employed in certain occupational groups were at increased risk for occupational
      M. tuberculosis infection.

PMID- 12210690
TI  - Occupation, exposure to chemicals and risk of gliomas and meningiomas in Sweden.
AB  - BACKGROUND: Occupational exposures may be related to the development of brain
      cancer. The objective was to estimate occupational-specific risk of gliomas and
      meningiomas among Swedish men and women gainfully employed in 1970 over the
      period 1971-1989, and the influence of occupational exposure to chemical
      substances. METHODS: A dataset linking cancer diagnoses from the Swedish national
      cancer register to occupational and demographical data obtained in the 1970
      census was used to fit log-linear Poisson models, in order to obtain relative
      risks adjusted by age, period, geographical area and town size. Exposure to 13
      chemicals was assessed using a Swedish job-exposure matrix. RESULTS: The main
      findings of this study among men were the increased risk of glioma with
      occupational exposure to arsenic, mercury, and petroleum products and of
      meningioma with lead. Women in occupational sectors with a higher socio-economic
      status showed an increased incidence of both, gliomas and meningiomas.
      CONCLUSIONS: Occupational exposure to some chemicals appeared to be related with
      an increased risk of glioma and meningioma in men. Exposures involved in glioma
      and meningioma development seemed to be different.

PMID- 12210692
TI  - Assessment of personal protective equipment use among Midwestern farmers.
AB  - BACKGROUND: Personal protective equipment (PPE) is readily available and widely
      recommended, yet usage among agricultural workers is largely unknown. METHODS: A
      mail survey of 2,483 farmers in six Midwestern states with telephone follow-up
      addressed PPE usage related to sun exposure, noise abatement, chain saw usage,
      welding and metal work, handling of large animals in and out of confinement
      facilities, feed handling, manure storage facilities, and mixing and applying
      chemicals. Summary statistics of survey responses were compiled. RESULTS: With
      the exception of welding masks, PPE usage was low. Farmers were satisfied with
      availability of PPE through local hardware and farm cooperatives, but the
      decision to use PPE was personal and influenced little by outside parties.
      CONCLUSION: PPE usage rates by farmers on Midwestern farms need to be increased.
      The desire of the individual farmer to reduce risk of personal injury or exposure
      should be targeted. The most effective venue will be local agricultural extension
      services.

PMID- 12210693
TI  - Prevalence of musculoskeletal symptoms and carpal tunnel syndrome among dental
      hygienists.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) and other work-related musculoskeletal
      disorders (MSDs) are common problems in general industry as well as dental
      hygiene. The purpose of this study is to determine the prevalence of CTS and
      other MSDs among dental hygienists. No previous studies involving dental
      hygienists have combined nerve conduction studies (NCS) and symptoms in their CTS
      case definitions. METHODS: Dental hygienists (N = 95) completed a symptom and job
      factors survey, hand symptom diagram, and underwent NCS across the wrist.
      RESULTS: At least one MSD was reported by 93%. Prevalence of CTS was 8.4%
      utilizing a case definition of symptoms and NCS, but 42% if defined by symptoms
      alone. Age, BMI, and the number of patients treated per day were significant
      factors associated with CTS. CONCLUSIONS: Dental hygienists are exposed to
      occupational factors that increase the risk of CTS. A case definition that does
      not include NCS overestimates CTS prevalence.

PMID- 12210694
TI  - Work-related cumulative trauma disorders of the upper extremity: navigating the
      epidemiologic literature.
AB  - BACKGROUND: Cumulative trauma disorder of the upper extremity (CTDUE) is an
      umbrella term used to describe disorders resulting from repeated use of the upper
      extremity over time rather than a specific incident. The primary purpose of this
      article is to summarize the literature regarding the rate of work-related CTDUE,
      while drawing attention to the various factors contributing to the wide range of
      reported findings. METHODS: The Cumulative Index to Nursing and Allied Health and
      Medline databases were searched for articles focusing on etiology or rates of
      occurrence of work-related CTDUE and their findings were summarized. RESULTS:
      Potential reasons for rising rates, a gender differential, and the substantial
      range in rates and rate ratios are delineated and important factors to consider
      when interpreting rates derived from workers' compensation data are detailed.
      CONCLUSIONS: Future research should attempt to correctly identify more specific
      categories of CTDUE in well-defined and accurately-quantified "at risk"
      populations to provide more meaningful information regarding the epidemiology of
      CTDUE and the effectiveness of control activities.

PMID- 12210696
TI  - Abstracts of the International Continence Society 32nd Annual Meeting.
      Heidelburg, Germany, 28-30 August 2002.

PMID- 12210695
TI  - Anything but beryllium: the beryllium industry's corruption of safety
      information.

PMID- 12210707
TI  - Mean arterial pressure (MAP): an alternative and preferable measurement to
      systolic blood pressure (SBP) in patients for hypotension detection during
      hemapheresis.
AB  - Current protocols utilize systolic blood pressure (SBP) of less than 80 mmHg as
      objective evidence of hypotension during hemapheresis. However, tissue
      hypoperfusion is the pathophysiologic endpoint of low blood pressure, and mean
      arterial pressure (MAP), rather than SBP, is the physiologic driving force behind
      blood flow to organs and tissues. It is thus hypothesized that MAP is more
      appropriate than SBP in the assessment of hypotension and that a threshold MAP
      can be utilized as a sensitive indicator of hypotension during hemapheresis.
      Thirty-one patients who experienced hypotension during hemapheresis over a 4.5
      year period reflecting forty-four hypotensive episodes were selected. The initial
      phase of each hemapheresis procedure provided baseline MAP and blood pressure
      (BP) measurements as control values. BP and MAP were then determined at the onset
      of subjective hypotension and compared to one another by using regression and
      sensitivity analyses. Correlation coefficients between SBP and MAP were found to
      be 0.8097 in baseline normotensive patients and 0.7725 in hypotensive patients.
      Sensitivity in the detection of hypotension was 0.09% for SBP equal to 80 mmHg
      and 56.81% for MAP equal to 70 mmHg. An SBP of 80 mmHg or less was therefore
      concluded to be a less sensitive and physiologically less appropriate measurement
      of hypotension than MAP. As a single value less than 70 mmHg or a series of
      successive measurements trending downward toward 70 mmHg, MAP provides an
      objective assessment of hypotension that may precede hemodynamic decompensation.

PMID- 12210708
TI  - Mononuclear cell collection in patients undergoing extra-corporeal photo
      chemotherapy for acute and chronic graft-vs.-host-disease (GvHD): comparison
      between COBE Spectra version 4.7 and 6.0 (AutoPBSC).
AB  - A constant improvement in the performance of blood cell separators has been
      observed in recent years, allowing better yields in peripheral blood stem cell
      collection (PBSC) either from healthy donors or for autologous purposes.
      Nevertheless, to our knowledge, no reports on the efficiency of mononuclear cell
      (MNC) collection in patients undergoing extra-corporeal photochemotherapy (ECP)
      for graft-vs.-host-disease (GvHD) have been published. We retrospectively
      investigated the efficiency of 167 MNC collections performed consecutively in 12
      patients between January 1999 and June 2001 by means of the COBE Spectra version
      4.7 (V 4.7) or version 6.0 (V 6.0), for 109 and 58 procedures, respectively. MNC
      fractional extraction (FE) was higher in the V 6.0 group compared to the V 4.7
      group : 0.59 +/- 0.21 vs. 0.51 +/- 0.22 (P < 0.05). However, platelet
      contamination was lower in the products obtained with V.6.0 compared to those
      obtained with V.4.7: 740 ( 630 x 10(3)/(L vs. 2,073 ( 1,429 x 10(3)/(L (P <
      0.05). Only two patients with acute GvHD, both from V 4.7 group, required post
      ECP platelet transfusion. The recently released version 6.0 allowed a
      satisfactory MNC yield with minimal platelet contamination in patients scheduled
      to undergo ECP for acute or chronic GvHD.

PMID- 12210709
TI  - Synchronised therapy and high-dose cyclophosphamide in proliferative lupus
      nephritis.
AB  - The aim of this open study was to compare the outcomes and side effects of
      plasmapheresis (PP) in patients with proliferative lupus nephritis treated with
      cyclophosphamide (Cyc) boluses. The study involved 28 consecutive patients. All
      of the patients met the ACR modified criteria for SLE and underwent a qualifying
      renal biopsy. In group I, patients were treated with synchronised therapy (PP, 50
      ml/kg, followed by pulse Cyc, 750 mg/m(2), repeated monthly for 6 months),
      whereas in group II, they were given only intermittent Cyc boluses (at the same
      dosage). The data were collected in the patients' records according to a
      standardised protocol. Patients were followed-up for a mean of 4 years. The
      disease-free survival was analysed using Kaplan-Meier estimated survival curves
      ([S(t)]). At the end of the 6-month treatment period, a statistically significant
      number of patients in group I (75%) was in complete remission in comparison to
      group II (31%) (P < 0.02), whereas at long-term follow-up, these percentages were
      similar (41% vs. 50%, P = n.s.). The main functional and immunological parameters
      showed a normalisation in both groups. The risk of a poor renal outcome
      significantly correlated with high serum creatinine levels at the onset of
      nephritis (P < 0.05). We documented a higher rate of infectious complications in
      group I. This study reports that synchronised therapy is useful in inducing a
      faster remission in patients with proliferative lupus nephritis. However, it is
      not superior to conventional therapy at long term follow-up analysis. Positive
      results should be reinforced by a long-term maintenance therapy.

PMID- 12210710
TI  - Therapeutic plasma exchange in recurrent focal segmental glomerulosclerosis
      following transplantation.
AB  - Focal segmental glomerulosclerosis (FSGS) recurs in 30% of renal allograft
      transplants with graft loss in half of the cases. A humoral factor may be
      implicated. We report on the use of therapeutic plasma exchange (TPE) in 11
      patients with recurrent FSGS post transplantation. Medical records from 1989-2000
      were reviewed for 11 adults transplanted for biopsy proven FSGS. Ten patients
      developed proteinuria (x: 6.1 g; range: 3-40 g/24 h) within 2 months of
      transplantation. In 1 patient, proteinuria (4 g) occurred 2 years post
      transplantation. Biopsy in six patients revealed early recurrent FSGS, while in
      five, suspected recurrence was based on clinical findings. Each patient received
      5-11 TPEs (x: 6) with the COBE Spectra, daily or on alternate days with 2.5-3.5 L
      5% albumin as the replacement fluid. In four, FFP was included because of
      coagulopathy. All received immunosuppression (IS) during and after TPE. A
      persistent drop in 24 h urine protein (U.P.) was observed in 10/11 patients.
      Seven had >70% drop in 24 h U.P. following the course of TPE, while three had a
      reduction of 45-50%. No change occurred in 1 patient. Follow-up (9 months-5
      years) of seven patients has shown a persistent U.P. of <1 g with successful
      allograft survival. In these patients, TPE appeared effective in early recurrent
      FSGS. The decrease in U.P. may result from combined TPE and IS. Although the
      disease is designated in category III by the ASFA, TPE should be considered early
      when FSGS recurrence is established.

PMID- 12210711
TI  - Long-term treatment of myasthenia gravis with immunoadsorption.
AB  - Acute treatment of myasthenic crisis with immunoadsorption (IA) or plasma
      exchange is well established. The efficiency of chronic apheresis therapy in
      myasthenia gravis (MG), however, and its efficacy in reducing concomitant
      potentially harmful immunosuppressive therapy, is unknown. We treated 13 patients
      with therapy-resistant MG or severe steroid or azathioprine therapy-related side
      effects, or both, with long-term IA [median, 38 (range: 16-59) months]. IA was
      performed every second day until partial remission was achieved (modified
      Osserman score <2). Subsequently, oral immunosuppressive therapy was reduced and
      the frequency of IA adapted to the clinical symptoms. After initiation of IA the
      mean (SEM) Osserman score decreased from 3.23 +/- 0.12 to 1.23 +/- 0.08 within 1
      month (P < 0.01). Mean azathioprine dose was reduced concomitantly from 89 +/-
      9.4 mg/day to 56 +/- 11 mg/day (P < 0.05), and mean prednisolone dose from 41 +/-
      7.6 mg/day to 22 +/- 8.5 mg/day (P < 0.05). After 36 months the number of IA
      sessions/month had been reduced from 4.81 +/- 0.24 to 2.64 +/- 0.4 (P < 0.05),
      the mean azathioprine dose to 25 +/- 17 mg/day and the mean prednisolone dose to
      9 +/- 3.6 mg/day. Six out of thirteen patients were weaned from IA after a median
      of 33 (range, 16-50) months and a decrease of the Osserman score to 0.33 +/-
      0.33. In these patients MG remained stable during a follow-up period of 28
      (range, 16-38) months. We conclude that long-term IA enables the reduction of
      oral immunosuppressants in patients with contraindications or resistance to
      steroid and azathioprine therapy. Furthermore, almost 50% of the patients can be
      weaned from IA with then substantial lower need of further immunosuppressive
      therapy.

PMID- 12210712
TI  - In hereditary hemochromatosis, red cell apheresis removes excess iron twice as
      fast as manual whole blood phlebotomy.
AB  - The current treatment of hereditary hemochromatosis (HH) consists of performing
      periodic manual whole blood phlebotomies. Erythroapheresis (EPH) is considered to
      be an alternative procedure if the classic treatment is contra-indicated. A
      prospective study of 13 consecutive cases of HH were included in a periodic EPH
      program with the aim of assessing the efficacy, feasibility, and tolerability of
      EPH in the treatment of HH by induction and maintenance. Iron depletion (ferritin
      <20 microg/l) was achieved in all patients after a mean of 6.7 +/- 2.9 months of
      treatment and a mean of 13.5 +/- 7.2 EPH sessions. The procedure was well
      tolerated and there were no complications. After a follow-up period of 10.5 +/-
      6.6 months, only four patients have required further maintenance sessions beyond
      6 months after completing the induction therapy. The efficacy, speed,
      tolerability, and more favorable schedule of an EPH program facilitate treatment
      of HH.

PMID- 12210713
TI  - Transfusion-related acute lung injury during plasma exchange: Suspecting the
      unsuspected.
AB  - Transfusion-related acute lung injury (TRALI) has been implicated with use of
      almost all types of blood products that contain variable amounts of plasma. Even
      though the reported incidence of TRALI is rare, its overall occurrence is thought
      to be more common, as less severe cases remain unreported. More TRALI cases are
      unrecognized and misdiagnosed due to lack of suspicion and absence of appropriate
      investigation. There are exceedingly rare reports of TRALI during plasma exchange
      despite the fact that liters of plasma may be used for replacement during a
      single procedure. We describe a mild case of TRALI during plasma exchange for
      thrombotic thrombocytopenic purpura in a 56-year-old woman, status post
      autologous hematopoietic stem cell transplant for non-Hodgkin's lymphoma. She
      developed severe rigors, peripheral cyanosis, hypoxia, and a transient diffuse
      pulmonary infiltrate. Of the 10 U of plasma used, one was from a multiparous
      female donor with HLA antibodies reactive with patient's granulocytes in
      immunofluorescence and agglutination assays. This case emphasizes the fact that
      the physicians and apheresis staff should consider TRALI in the differential
      diagnosis for patients developing respiratory distress during or soon after the
      procedure. Diagnosing TRALI has implications not only for the plasma exchange
      recipient, but also for the management of donors found to have leukocyte
      antibodies.

PMID- 12210714
TI  - Direct hemoperfusion using a polymyxin B immobilized column improves acute
      respiratory distress syndrome.
AB  - Acute respiratory distress syndrome (ARDS) is characterized by a high mortality
      rate. We have studied whether direct hemoperfusion using a polymyxin B
      immobilized fiber column (PMX-DHP) is effective for acute lung injury (ALI) and
      ARDS. Two ALI and eighteen ARDS patients were evaluated, four congestive heart
      failure (CHF) patients were evaluated as cardiogenic pulmonary edema, and we
      retrospectively compared the outcome with ten patients with ARDS who had been
      hospitalized between 1990 and 1998 as the untreated group. PMX-DHP was carried
      out twice at a rate of 80-100 ml/minute for 2 hours, with a time interval of
      approximately 24 hours. We monitored systolic blood pressure (BP), diastolic BP,
      and the PaO(2)/FIO(2) (PF) ratio before and after PMX-DHP treatment. The
      mortality was classified if patients were alive at day 30 after initiating PMX
      DHP. The mortality of ARDS patients was approximately 20%. Systolic BP increased
      significantly from 106 +/- 20 to 135 +/- 21 and to 125 +/- 20 mmHg on the
      following day. Diastolic BP increased from 61 +/- 16 to 78 +/- 15, and to 72 +/-
      12 mmHg. The PF ratio increased significantly from 125 +/- 54 to 153 +/- 73, and
      163 +/- 78 Torr. CHF patients did not reveal improvement of systolic, diastolic
      BP, and PF ratio after PMX-DHP. Eight of ten patients in the untreated group died
      through exacerbated ARDS. In ARDS patients, PMX-DHP improved circulatory
      disturbance and oxygenation despite the underlying diseases. The mortality
      improved compared with that before induction of PMX-DHP.

PMID- 12210715
TI  - Calculated platelet dose: Is it useful in clinical practice?
AB  - The corrected count increment (CCI) can standardize assessment of platelet
      transfusions by correcting for patient's body surface area (BSA) and platelet
      dose (PD). By using a fixed CCI and a desired post-transfusion platelet count,
      CCI formula can be used to calculate PD. Our transfusion service has used the
      following formula since May 1990, to determine the number of platelet units to
      transfuse in non-bleeding patients: 1 where, 7,000 is expected platelet count
      increment per unit transfused, and 1.7 is BSA in square meters in a normal adult.
      To evaluate its usefulness, a retrospective review was performed of all 2,202
      platelet transfusions at our level-one trauma center, between 1/1/98 and
      12/31/00. Eighty-three transfusions in 69 adult patients, in which a calculated
      PD was determined prior to transfusion, were evaluated for platelet increments at
      1, 1-18, or 18-24 hours post-transfusion. Transfusions that used the calculated
      PD (n = 49) were compared with those that were based on clinical judgment alone
      (n = 34). These two groups were comparable in their pre-transfusion platelet
      counts, ABO compatibility, and unit storage duration. The mean calculated PD
      transfused in the first group was 6 U +/- 1 standard deviation, which was not
      different from the second group (P = 0.2). There was no difference in the
      platelet count increments at 1, 1-18, or 18-24 hours post-transfusion. This study
      suggests that using a PD based on the CCI formula does not reduce platelet usage
      when the routine PD is six or less platelet concentrates.

PMID- 12210716
TI  - Runx2, a multifunctional transcription factor in skeletal development.
AB  - The identification of Runx2 (runt-related protein 2) function has greatly
      advanced the understanding of skeletal development over the last 5 years. Runx2
      is regulated transcriptionally and post-translationally through the activity of
      many identified factors, although, the physiological significance of each remains
      to be demonstrated. The interaction of Runx2 with other transcription factors and
      cofactors has been shown to be important in Runx2-dependent gene regulation.
      Runx2 plays important roles in multiple steps of skeletal development. Runx2
      determines the lineage of osteoblasts from multipotent mesenchymal cells,
      enhances osteoblast differentiation at an early stage, and inhibits osteoblast
      differentiation at a late stage. Runx2 plays crucial roles in chondrocyte
      maturation and in the specification of cartilage phenotypes. Furthermore, Runx2
      is involved in vascular invasion into cartilage and osteoclastogenesis.
      Therefore, the determination of Runx2 function and the investigation of the
      cascades of Runx2-dependent gene regulation are important in the elucidation of
      skeletal biology.

PMID- 12210717
TI  - Further characterization of human fetal osteoblastic hFOB 1.19 and hFOB/ER alpha
      cells: bone formation in vivo and karyotype analysis using multicolor fluorescent
      in situ hybridization.
AB  - We have previously generated an immortalized human fetal osteoblastic cell line
      (hFOB) using stably transfected temperature sensitive SV40 T-antigen (Harris et
      al. [1995a] J. Bone. Miner. Res. 10:178-1860). To characterize these cells for
      phenotypic/genotypic attributes desired for a good cell model system, we
      performed karyotype analysis by multicolor fluorescent in situ hybridization (M
      FISH), their ability to form bone in vivo without developing cell transformation,
      and finally their ability to form extracellular matrix formation in vitro. The
      karyotype analysis of hFOB cells revealed structural or numeric anomalies
      involving 1-2 chromosomes. In contrast, the human osteosarcoma MG63 cells
      displayed multiple, and often complex, numeric, and structural abnormalities.
      Subcutaneous injection of hFOB cells in the presence of Matrigel into nude mice
      resulted in bone formation after 2-3 weeks. Electron microscopic analysis of the
      extracellular matrix deposited by hFOB cells in culture revealed a parallel array
      of lightly banded fibrils typical of the fibrillar collagens such as type I and
      III. These results demonstrate that the hFOB cell line has minimal chromosome
      abnormalities, exhibit the matrix synthetic properties of differentiated
      osteoblasts, and are immortalized but non-transformed cell line. These hFOB cells
      thus appear to be an excellent model system for the study of osteoblast biology
      in vitro.

PMID- 12210718
TI  - Morphological changes induced by extracellular matrix are correlated with
      maturation of rat small hepatocytes.
AB  - Small hepatocytes (SHs), which are known to be hepatic progenitor cells, were
      isolated from an adult rat liver. SHs in a colony sometimes change their shape
      from small to large and from flat to rising/piled-up. The aim of the present
      study is to clarify whether the alteration of cell shape is correlated with the
      maturation of SHs and whether extracellular matrix (ECM) can induce the
      morphological changes of SHs. We used liver-enriched transcription factors
      (LETFs) such as hepatocyte nuclear factor (HNF) 4 alpha, HNF6, CCAAT/enhancer
      binding proteins (C/EBP) alpha, and C/EBP beta, tryptophan 2,3-dioxygenase (TO),
      and serine dehydratase (SDH) as markers of hepatic maturation. To enrich the
      number of SH colonies, the colonies were isolated from dishes and replated.
      Replated colonies proliferated and the average number of cells per colony was
      about five times larger at day 9 than at day 1. When the cells were treated with
      laminin, type IV collagen, a mixture of laminin and type IV collagen, Matrigel or
      collagen gel (CG), only the cells treated with Matrigel dramatically changed
      their shape within several days and had reduced growth activity, whereas the
      cells treated with other ECM did not. HNF4 alpha, HNF6, C/EBP alpha, C/EBP beta,
      and TO were well expressed in the cells treated with Matrigel. Furthermore,
      addition of both glucagon and dexamethasone dramatically induced the expression
      of SDH mRNA and protein in the cells treated with Matrigel. In conclusion,
      morphological changes of SHs may be correlated with hepatic maturation and
      basement membrane (BM)-like structure may induce the morphological changes of
      SHs.

PMID- 12210719
TI  - Arsenic induces oxidative stress and activates stress gene expressions in
      cultured lung epithelial cells.
AB  - Chronic exposure to low levels of arsenic can cause lung cancer. However, the
      cellular and molecular mechanisms for lung cell transformation in response to
      arsenic are not known. These studies investigated the hypothesis that low levels
      of arsenic increase intracellular oxidant levels, promote production of mitogenic
      transcription factors and antioxidant enzymes. Initially, arsenic decreased GSH
      cellular level and rapidly increased to 280% of GSH level in nonexposed lung
      cells in 24 h. Buthionine sulfoximine (BSO) potentiated the arsenic toxicity of
      lung epithelial cells (LEC). Exposure of LEC to 5 microM arsenite cause time
      dependent increase in gamma-glutamylcysteine synthetase (gamma-GCS) expression.
      Our data demonstrated that arsenic induced the heavy subunit of gamma-GCS (gamma
      GCS-HS) mRNA levels as early as 4 h as compared to the control level. It
      significantly increased (sixfolds) gamma-GCS-HS mRNA expression after 8 h of
      treatment. The activation of AP-1 transcription factors may also play a
      regulatory role in this process. Significant elevations in c-fos and c-jun mRNA
      levels were observed within 30 min after exposure to arsenic and by enhancement
      of AP-1 DNA binding activity and transactivation activity. Responsiveness of LEC
      to oxidative stress caused by arsenic exposure was further evaluated with
      mobility shift assay involving redox-sensitive transcription factor NF-kappa B.
      The specificity of binding was verified by an antibody-supershift. The NF-kappa B
      DNA binding activities increased more than twofold 30 min after exposure to
      arsenic and returned to control levels after 4 h of treatment. It remains to be
      determined whether NF-kappa B plays a role in the As-induced apoptosis or
      alternatively in attempting to protect the cells from As-induced cell death by
      upregulating the expression of resistance factors.

PMID- 12210720
TI  - Microgravity modifies protein kinase C isoform translocation in the human
      monocytic cell line U937 and human peripheral blood T-cells.
AB  - Individual protein kinase C (PKC) isoforms fulfill distinct roles in the
      regulation of the commitment to differentiation, cell cycle arrest, and apoptosis
      in both monocytes and T-cells. The human monocyte like cell line U937 and T-cells
      were exposed to microgravity, during spaceflight and the translocation (a
      critical step in PKC signaling) of individual isoforms to cell particulate
      fraction examined. PKC activating phorbol esters induced a rapid translocation of
      several PKC isoforms to the particulate fraction of U937 monocytes under
      terrestrial gravity (1 g) conditions in the laboratory. In microgravity, the
      translocation of PKC beta II, delta, and epsilon in response to phorbol esters
      was reduced in microgravity compared to 1 g, but was enhanced in weak
      hypergravity (1.4 g). All isoforms showed a net increase in particulate PKC
      following phorbol ester stimulation, except PKC delta which showed a net decrease
      in microgravity. In T-cells, phorbol ester induced translocation of PKC delta was
      reduced in microgravity, compared to 1 g, while PKC beta II translocation was not
      significantly different at the two g-levels. These data show that microgravity
      differentially alters the translocation of individual PKC isoforms in monocytes
      and T-cells, thus providing a partial explanation for the modifications
      previously observed in the activation of these cell types under microgravity.

PMID- 12210721
TI  - Identification of cultured progenitor cells from human marrow stroma.
AB  - The marrow stromal cells (MSC) are essential for regulation of bone remodeling
      and hematopoiesis. It is of prime importance to isolate MSC and to expand the
      proliferating cells ex vivo. In this study, we analyzed cultured MSC for various
      cellular parameters, including cell morphology, cell cycle, and expression of
      cell surface antigens by flow cytometry. MSC were divided based on cell size to
      small (S-cells) and large (L-cells) and were visualized by light and electron
      microscope. The S-cells were proliferating cells correlated with G0/G1 phase of
      cell cycle, and expressed cFOS. The expression of surface markers CD-34, -44, 
      51, -61, -62E, -62P, -62L was quantified using flow cytometry. CD-44 was
      ubiquitously expressed by S and L cells, CD-51 and -61 were expressed by 30%-38%
      of S-cells. CD-34 and -62 expressed 20% positive of the analyzed cells that were
      of the proliferating progenitors (S-cells). This study enables the identification
      of subpopulations from MSC with special attention paid to the proliferating cells
      from ex vivo cultures of marrow stroma.

PMID- 12210722
TI  - Purification and characterization of the active form of tyrosine hydroxylase from
      mesangial cells in culture.
AB  - The capacity of mesangial cells (MC) to produce catecholamines (CAs) has been
      investigated in our laboratory. To study the CA cascade, it is necessary to
      examine some steps in their metabolic pathway. Tyrosine hydroxylase (TH)
      catalyzes the rate-limiting step in the biosynthesis of these biogenic amines
      (dopamine (DA), norepinephrine (NE), and epinephrine (EPI)). Since the glomerular
      mesangium is their target in the regulation of renal sodium transport and renin
      secretion, the aim of the study was to determine the presence of TH in these
      cells in culture. The CA levels were detected in immortalized MC by high
      performance liquid chromatography with electrochemical detection. The following
      concentrations were found in the intracellular region and in the medium,
      respectively: NE = 284 +/- 31 and 134 +/- 22, EPI = 75 +/- 14 and 22 +/- 5, and
      DA = 42 +/- 14, 40 +/- 20 pg/mg cell protein. The enzymatic activity of the cell
      lysate and medium was measured based on L-dopa formation. In the presence of o
      phenanthroline, both samples presented 39% inhibition. The biopterin was detected
      in the intracellular and in the medium (64.87 and 631.99 pmol/mg protein,
      respectively) using high-performance liquid chromatography with ultraviolet
      detection. The cell lysate was submitted to a DEAE-Sephacel column, followed by
      gel filtration, and Heparin-Sepharose. TH was purified 613.16-fold with a
      specific activity of 466.0 pg/mg cell protein. Immunoblotting using monoclonal
      antibody revealed the presence of TH in the different purification steps.
      Purified TH was sequenced, presenting an alignment with amino-terminal sequence
      of mouse enzyme. Our results demonstrated the presence of active TH in MC,
      suggesting that these cells are able to produce CA "in vivo", and establishing a
      convenient purification method for TH that can be applied to the study of the
      molecular properties of the enzyme modified "in vivo" by different physiological
      and pathophysiological stimuli.

PMID- 12210723
TI  - C2PA is a nuclear protein implicated in the heat shock response.
AB  - C2PA is a protein of unknown function that is expressed in spermatocytes. PDZ
      RGS3 is a signaling molecule whose PDZ domain binds Ephrin-B2 and mediates
      reverse signaling of this protein. C2PA and PDZ-RGS3 have identical PDZ domains.
      To explore the function of C2PA, we compared it with PDZ-RGS3 with respect to
      tissue distribution, subcellular localization, and biochemistry. C2PA is
      expressed only in testis, whereas PDZ-RGS3 is expressed in various tissues
      including brain, heart, lung, liver, spleen, kidney, small intestine, skeletal
      muscles, and testis. These proteins also differ in their subcellular
      distribution, in that PDZ-RGS3 is cytosolic while C2PA is exclusively nuclear.
      C2PA is distributed diffusely in the nucleus and forms a few foci at 37 degrees
      C. However, when cells are exposed to 42 degrees C, the number of C2PA foci is
      increased. These heat shock-induced foci colocalize with CREB-binding protein and
      heat shock factor-1. In contrast, the distribution of PDZ-RGS3 does not change
      during heat stress. When overexpressed, C2PA induces heat shock response element
      (HSE)-dependent gene transcription, whereas PDZ-RGS3 does not. These data suggest
      that the function of C2PA is distinct from that of PDZ-RGS3, and that C2PA may be
      involved in the heat shock response in testis.

PMID- 12210724
TI  - Glucose-dependent regulation of osteoclast H(+)-ATPase expression: potential role
      of p38 MAP-kinase.
AB  - Bone resorption is glucose concentration dependent. Mechanisms regulating glucose
      dependent increases in bone resorption have not been identified. Glucose
      activates p38 MAP-kinase in other cells and since MAP kinases activate
      transcription factors, we hypothesized that glucose-stimulated bone resorption
      may be modulated by increased expression of the vacuolar H(+)-ATPase. Glucose
      activates osteoclast p38 MAP-kinase in a time and concentration-dependent manner
      as determined by Western analysis with phospho-specific p38 antibody while total
      p38 levels are unchanged. The K0.5 for glucose-dependent activation of p38 MAP
      kinase is approximately 7 mM, activation is maximal at 30 min and is elevated but
      returning to basal levels by 60 min. The concentration-dependent increase in H(+)
      ATPase expression was confirmed by Northern analysis. The specific inhibitor of
      p38 MAP-kinase, SB203580, inhibited glucose transport in osteoclasts, as well as
      glucose concentration-dependent increases in bone resorption and expression of
      H(+)-ATPase A and B subunits. Glucose had no effect on calmodulin expression
      levels that are regulated in response to other environmental changes. The glucose
      stimulated increase in H(+)-ATPase mRNA expression is a specific response to
      glucose since glucose has little effect on G3PDH mRNA levels. We conclude that
      glucose regulates osteoclast H(+)-ATPase expression by a mechanism likely to
      involve p38 MAP-kinase.

PMID- 12210725
TI  - ERK activation and alpha v beta 3 integrin signaling through Shc recruitment in
      response to mechanical stimulation in human osteoblasts.
AB  - Osteoblast growth and differentiation are critical processes for bone development
      and maintenance, and are regulated by both humoral and mechanical factors.
      Humoral (hormonal) factors can affect gene transcription via MAPkinases, e.g.,
      extracellular signal-regulated kinase (ERK). We studied whether the ERK pathway
      is also involved in processing mechanical inputs in human bone cells. Exposing
      MG63 cells to physiologically relevant levels of fluid flow resulted in ERK
      phosphorylation. Genistein blocked this response, indicating that it is dependent
      on tyrosine phosphorylation. Furthermore, alpha v beta 3 integrins were activated
      in response to fluid flow, as shown by recruitment of adaptor molecule Shc and
      clustering of alpha v beta 3 in focal adhesion-like structures. Antibodies
      blocking formation of beta 1 or beta 3 integrin-matrix interactions or RGD
      peptides could not inhibit fluid flow-induced ERK phosphorylation, suggesting
      that formation of new integrin-matrix interactions is not essential for this
      response and that other upstream mechanosensors regulate induction of ERK
      phosphorylation in response to fluid flow in human bone cells.

PMID- 12210726
TI  - Okadaic acid stimulates osteopontin expression through de novo induction of AP-1.
AB  - Osteopontin, a major non-collagenous bone matrix protein, is strikingly
      upregulated in various tissues under certain pathologic conditions, including
      cancer. However, the mechanism of upregulation of the osteopontin gene in tumor
      cells remains unclear. Okadaic acid, a strong non-phorbol ester tumor promoter,
      is known to stimulate the expression of osteopontin. The aim of the present study
      was to understand the mechanism by which okadaic acid regulates osteopontin gene
      expression. Okadaic acid stimulated osteopontin mRNA expression in several cell
      lines within 3 h, and the increase in osteopontin mRNA was sustained for 24 h.
      New protein synthesis was required for the okadaic acid-elicited increase in
      osteopontin mRNA expression. A serial promoter deletion study showed that the
      okadaic acid-response element is located between positions -265 and -73, a
      sequence that includes the Runx2, Ets-1, and AP-1 binding sequences. Okadaic acid
      increased the mRNA expression of AP-1 components but not of Runx2 or Ets-1. Site
      directed mutagenesis and electrophoretic mobility shift assays confirmed that
      protein binding of the AP-1 consensus sequence is necessary for the okadaic acid
      mediated osteopontin gene upregulation. These results indicate that de novo
      induction of the oncoprotein AP-1 is required for okadaic acid-stimulated
      osteopontin gene upregulation.

PMID- 12210727
TI  - Cyclic AMP mediated GSTP1 gene activation in tumor cells involves the interaction
      of activated CREB-1 with the GSTP1 CRE: a novel mechanism of cellular GSTP1 gene
      regulation.
AB  - The human GSTP1 gene is frequently over-expressed in many human cancers and the
      expression increases with tumor progression and is associated with a more
      aggressive biology, poor patient survival, and resistance to therapy. The
      molecular regulation of the human GSTP1 gene during malignancy is, however, still
      not well understood. Recently, we reported the presence of a cAMP response
      element (CRE) in the 5'-region of the human GSTP1 gene, raising the possibility
      that the cAMP signaling pathway, frequently aberrant in human cancers, may play
      an important role in the transcriptional activation of the GSTP1 gene in human
      tumors. In this study, we report that the GSTP1 gene is an early cAMP response
      gene. Treatment of cells of the human lung carcinoma cell line, Calu-6, with 25
      microM forskolin to activate the cAMP pathway resulted in a rapid and significant
      (sevenfold after 30 min) increase in GSTP1 gene transcripts, which peaked at 12
      fold after 4 h. The forskolin-activated GSTP1 transcription in Calu-6 cells was
      suppressed dose-dependently by a 2-h pre-treatment with 0.1, 1.0, and 10 microM
      of the adenylate cyclase inhibitor, 2', 5'-dideoxyadenosine. Western blot
      analysis showed a rapid, fivefold increase, in GSTP1 protein levels after
      treatment with 25 microM forskolin, with a peak at 2 h post-treatment. The levels
      of phosphorylated CRE (Ser133) binding protein-1 (CREB-1) increased rapidly,
      sevenfold at 30 min, and reached 10-fold at 4 h following forskolin treatment.
      Intracellular cAMP levels also increased rapidly reaching 12-fold at 30 min. Gel
      mobility shift and supershift assays and DNase/footprinting analyses demonstrated
      that CREB-1 bZIP and CREB-containing nuclear extracts recognized the GSTP1 CRE
      with high affinity and specificity. Binding of CREB-1 bZIP to the GSTP1 CRE was
      abolished when the GSTP1 CRE sequence 5'-CGTCA-3', was mutated at the core
      nucleotides. Finally, transfection studies using luciferase plasmid constructs
      showed the GSTP1 CRE to be required for the cAMP-activated gene expression.
      Together, these findings describe a novel cAMP- and CREB-1-mediated mechanism of
      transcriptional regulation of the GSTP1 gene and suggest that this may be an
      important mechanism underlying the increased GSTP1 expression observed in tumors
      with an aberrant cAMP signaling pathway and in normal cells under conditions of
      stress, associated with increased intracellular cAMP.

PMID- 12210728
TI  - Fanconi anemia protein complex is a novel target of the IKK signalsome.
AB  - Fanconi anemia (FA), a genetic disorder predisposing to aplastic anemia and
      cancer, is characterized by hypersensitivity to DNA-damaging agents and oxidative
      stress. Five of the cloned FA proteins (FANCA, FANCC, FANCE, FANCF, FANCG) appear
      to be involved in a common functional pathway that is required for the
      monoubiquitination of a sixth gene product, FANCD2. Here, we report that FANCA
      associates with the IkappaB kinase (IKK) signalsome via interaction with IKK2.
      Components of the FANCA complex undergo rapid, stimulus-dependent changes in
      phosphorylation, which are blocked by kinase-inactive IKK2 (IKK2 K > M). When
      exposed to mitomycin C, cells expressing IKK2 K > M develop a cell cycle
      abnormality characteristic of FA. Thus, FANCA may function to recruit IKK2, thus
      providing the cell a means of rapidly responding to stress.

PMID- 12210729
TI  - Runx1, c-Myb, and C/EBPalpha couple differentiation to proliferation or growth
      arrest during hematopoiesis.
AB  - Immature hematopoietic precursors proliferate as they differentiate, whereas
      terminal differentiation is associated with cell cycle arrest. Stem cell lineage
      commitment and subseqent maturation is regulated predominantly by transcription
      factors. Runx1 and c-Myb act in early stage hematopoietic cells to both stimulate
      proliferation and differentiation, whereas C/EBPalpha, and perhaps other C/EBP
      family members, block progression from G1 to S and induce terminal maturation.
      Coupling of differentiation to either proliferation or growth arrest by
      transcription factors is likely an important regulatory mechanism in multiple
      developmental systems.

PMID- 12210730
TI  - Interaction of the retinoblastoma gene product, RB, with cyclophilin A negatively
      affects cyclosporin-inhibited NFAT signaling.
AB  - The retinoblastoma susceptibility gene product, p105Rb (RB), is generally
      believed to be an important regulator in the control of cell growth,
      differentiation, and apoptosis. Several cellular factors that form complexes with
      RB and exert their cellular regulatory functions have been identified, such as
      the newly identified RB:cyclophilin A (CypA) complex. The physical interactions
      between RB and CypA were demonstrated by glutathione S-transferase affinity
      matrix binding assays and immunoprecipitation, followed by Western blot analyses.
      The N-terminal region of CypA mediated the interaction with RB, whereas the
      region upstream of the A-pocket of RB was required for binding to CypA. Ectopic
      expression of RB into Jurkat cells partially blocks the function of cyclosporin
      (CsA) to inhibit nuclear factor for activation of T cell (NFAT) activation by
      phorbol ester (PMA) plus ionomycin A (IA), suggesting that RB may prevent CsA
      inhibition of T lymphocyte activation. These results are further evidenced by the
      effect of RB on both calcineurin (CN) and NFAT binding activity in vitro,
      suggesting that the interaction of RB with CypA interferes with the CsA:CypA
      complex and blocks CsA-inhibited CN activity. These data reveal the functional
      link between RB and CypA and their involvement in T cell activation signaling.

PMID- 12210731
TI  - Detection and characterization of RANK ligand and osteoprotegerin in the thyroid
      gland.
AB  - Receptor activator of NF-kappaB (RANK) ligand (RANKL) and osteoprotegerin (OPG)
      play essential roles in bone metabolism and immune responses. RANKL activates
      RANK, which is expressed by osteoclasts and dendritic cells (DC), whereas OPG
      acts as its decoy receptor. The role of RANKL and OPG in thyroid physiology is
      unclear. Northern analysis revealed pronounced OPG mRNA levels in normal human
      thyroid. By contrast, RANKL mRNA levels were most abundant in lymph node and
      appendix, and low in the thyroid. In the human thyroid follicular cell line XTC
      and in primary human thyroid follicular cells, OPG mRNA levels and protein
      secretion were upregulated by interleukin (IL)-1beta (33-fold), tumor necrosis
      factor (TNF)-alpha (eightfold), and thyrotropin (TSH) (threefold). RANKL mRNA was
      stimulated in XTC by IL-1beta and TNF-alpha, but inhibited by TSH. Conditioned
      medium harvested from IL-1beta-treated XTC (containing high concentrations of
      OPG) inhibited RANKL-induced CD40 upregulation and cluster formation of DC. OPG
      mRNA levels were three times more abundant in surgical thyroid specimens of
      Graves' disease as compared to other thyroid diseases. Our data suggest that
      RANKL and OPG are produced in the thyroid gland by thyroid follicular cells, are
      regulated by cytokines and TSH, and are capable of modulating dendritic cell
      functions. Thus, these cytokines may represent important local immunoregulatory
      factors involved in the pathogenesis of autoimmune thyroid diseases.

PMID- 12210732
TI  - Th1 and Th2 cytokines exert regulatory effects upon islet microvascular areas in
      the NOD mouse.
AB  - In this study, we show that intra- and peri-islet microvascular areas undergo
      different changes during the islet inflammation in the nonobese diabetes-prone
      female mice. Actually, although the islet vascular area (IVA) considerably
      decreases while the infiltration progresses, at 15 weeks of age, the peri-islet
      vascular bed is unexpectedly and significantly increased. On the contrary, the
      intra-IVA is significantly decreased, due to vessel dilation. Later, by 20-25
      weeks of age, a decrease of both IVA occur, due to a significant islet beta cell
      loss. Moreover, a dramatic fall of natural free radical scavenger values, which,
      in turn, exert an influence upon vessels, is observed. These effects are
      completely counteracted by the administration of IL-4, a Th2 protective cytokine;
      IL-10, another putative Th2 cytokine, exerts direct effects upon endothelial cell
      (EC) function, as shown by the increase of endothelial nitric oxide synthase
      (eNOS) mRNA transcripts and by the release of endothelial NO which, in turn,
      exert vasodilatory effects; moreover, this cytokine significantly upregulates
      adhesion molecules on endothelia. On the other hand, IL-1beta, a Th1
      proinflammatory cytokine, dramatically increases nitrite and nitrate levels, as
      well as inducible nitric oxide synthase (iNOS) transcripts and also upregulates
      islet ICAM-1 expression as well as circulating ICAM-1 levels. Taken together, our
      findings clearly show that cytokines and islet endothelia are directly involved
      in the pathophysiology of the disease. Their reciprocal influence gives new
      insight to understand the role of microvasculature during islet beta cell attack.

PMID- 12210733
TI  - Constitutive activation of met kinase in non-small-cell lung carcinomas
      correlates with anchorage-independent cell survival.
AB  - Lung cancer is currently the most frequent cause of cancer death in North
      America. Hepatocyte growth factor (HGF) and its receptor Met are frequently over
      expressed in non-small-cell lung carcinomas (NSCLC), but their potential role in
      tumor progression is not clearly known. To assess the role of HGF/Met signaling
      in lung carcinomas, we have examined the expression, activation status, and
      function of Met in NSCLC cell lines (n = 7), established from primary tumors or
      pleural fluids of cancer patients. We observed Met expression in three NSCLC cell
      lines, two of which exhibited constitutive tyrosine-phosphorylation of Met, and
      Met kinase activity. In addition, the observed constitutive activation of Met was
      sustained under anchorage-independent conditions, and correlated with
      phosphatidyl inositol 3-kinase-dependent cell survival. Immunoreactive HGF-like
      protein was secreted by two Met-positive and two Met-negative NSCLC cell lines.
      However HGF activity, as determined by the ability to induce cell scattering and
      tyrosine-phosphorylation of Met in reporter cell lines, was detected in
      conditioned medium from only one Met-negative NSCLC cell line: none of the
      conditioned media from Met-expressing NSCLC cell lines showed detectable HGF
      activity. Thus, constitutive activation of Met in NSCLC cell lines may occur at
      least in part through intracrine, or HGF-independent mechanisms. Interestingly,
      additional paracrine stimulation with exogenous recombinant HGF was required for
      DNA synthesis and correlated with increased activation of ERK1/2 in all Met
      positive NSCLC cell lines, regardless of the basal activation status of Met.
      These findings indicate that a medium level of constitutive activation of Met
      occurs in some NSCLC cell lines, and correlates with survival of detached
      carcinoma cells; whereas additional paracrine stimulation by recombinant HGF is
      required for DNA synthesis. Thus constitutive and paracrine activation of Met may
      provide complementary signals that promote survival and proliferation,
      respectively, during tumor progression of NSCLC.

PMID- 12210734
TI  - Characterization of a 1,25(OH)2-vitamin D3-responsive capacitative Ca2+ entry
      pathway in rat osteoblast-like cells.
AB  - We investigated the existence of a capacitative Ca2+ entry (CCE) pathway in ROS
      17/2.8 osteoblast-like cells and its responsiveness to 1,25-dihydroxy-vitamin D3
      [1,25(OH)2D3]. Depletion of inner Ca2+ stores with thapsigargin or 1,25(OH)2D3 in
      the absence of extracellular Ca2+ transiently elevated cytosolic Ca2+ ([Ca2+]i);
      after recovery of basal values, Ca2+ re-addition to the medium markedly increased
      Ca2+ entry, reflecting pre-activation of a CCE pathway. Recovery of the Ca2+
      overshoot that followed the induced CCE was mainly mediated by the plasma
      membrane Ca2+-ATPase. Addition of 1,25(OH)2D3 to the declining phase of the
      thapsigargin-induced CCE did not modify further [Ca2+]i, indicating that steroid
      activation of CCE was dependent on store depletion. Pre-treatment with 1 microM
      Gd3+ inhibited 30% both thapsigargin- and 1,25(OH)2D3-stimulated CCE, whereas 2.5
      microM Gd3+ was required for maximal inhibition ( approximately 85%). The
      activated CCE was permeable to both Mn2+ and Sr2+. Mn2+ entry sensitivity to Gd3+
      was the same as that of the CCE. However, 1-microM Gd3+ completely prevented
      capacitative Sr2+ influx, whereas subsequent Ca2+ re-addition was reduced only
      30%. These results suggest that in ROS 17/2.8 cells CCE induced by thapsigargin
      or 1,25(OH)2D3 is contributed by at least two cation entry pathways: a Ca2+/Mn2+
      permeable route insensitive to very low micromolar (1 microM) Gd3+ accounting for
      most of the CCE and a minor Ca2+/Sr2+/Mn2+ permeable route highly sensitive to 1
      microM Gd3+. The Ca2+-mobilizing agonist ATP also stimulated CCE resembling the
      Ca2+/Sr2+/Mn2+ permeable entry activated by 1,25(OH)2D3. The data demonstrates
      for the first time, the presence of a hormone-responsive CCE pathway in an
      osteoblast cell model, raising the possibility that it could be an alternative
      Ca2+ influx route through which osteotropic agents influence osteoblast Ca2+
      homeostasis.

PMID- 12210735
TI  - Role of c-fos in the regulation of type X collagen gene expression by PTH and
      PTHrP: localization of a PTH/PTHrP-responsive region in the human COL10A1
      enhancer.
AB  - PTH and PTHrP have been shown to inhibit maturation of growth plate chondrocytes
      and the expression of type X collagen. In order to examine the regulatory
      mechanisms involved, fetal bovine growth plate chondrocytes were incubated for 24
      48 h under serum-free conditions with PTH and PTHrP and various aminoterminal,
      midregional, and carboxyterminal fragments of these hormones. Analysis of type X
      collagen mRNA levels by Northern hybridization showed a significant suppression
      by PTH (1-84), PTH (1-34), and PTHrP (1-40), but not by PTH (28-48) or PTH (53
      84). PTH fragment (3-34) did not reduce alpha1(X) mRNA levels, while bis
      indolylmaleimide, an inhibitor of the protein-kinase C pathway, did not affect
      alpha1(X) mRNA suppression by PTH, supporting the notion that the inhibition of
      type X collagen expression by PTH involves predominantly the adenylate cyclase
      pathway of the PTH/PTHrP-receptor. Since PTH and PTHrP have been shown to induce
      c-fos in osteoblasts and chondrocytes, the possibility was tested that c-fos
      mediated the suppressive effect of PTH/PTHrP on collagen X expression. In fetal
      bovine hypertrophic chondrocytes PTH (1-34), but not PTH (3-34) nor the
      midregional or C-terminal PTH fragments induced c-fos expression. In order to
      identify cis- and trans-acting elements in the COL10A1 gene involved in c-fos
      mediated inhibition of collagen X expression by PTH/PTHrP, reporter gene
      constructs carrying various fragments of the human COL10A1 promoter coupled to
      the luciferase gene were transfected into hypertrophic chondrocytes. A tissue
      specific, strong enhancer region, which we had previously located in the promoter
      of the human type X collagen gene COL10A1, was further narrowed down to a 530-bp
      sequence, located between - 1,870- and - 2,407 bp upstream of the transcription
      start site. The transcriptional activity of this enhancer element in transfected
      hypertrophic chondrocytes was significantly reduced after incubation with PTH (1
      34) or PTHrP (1-40). Transcription of these reporter genes was also inhibited
      when chondrocytes were cotransfected with a c-fos expression vector. These
      results indicate the presence of a PTH/PTHrP responsive element in the human
      COL10A1 enhancer, which may be represented by multiple putative AP-1 sites
      located in this region.

PMID- 12210736
TI  - Associated proteins of lens adherens junction.
AB  - Cytoplasmic proteins associated with adherens junctions were identified in the
      chicken ocular lens. The catenins, alpha, beta, and gamma, were present in
      epithelial and fiber cells, although their pattern of distribution changed with
      fiber cell differentiation. The sharp decline in alpha-catenin with fiber cell
      formation and the increasing Triton-insolubility of N-cadherin suggests that
      another subtype of alpha-catenin exists in the lens.

PMID- 12210737
TI  - Flow cytometric detection of total and serine 473 phosphorylated Akt.
AB  - The evaluation of regulatory proteins is important for biological studies and is
      also established as a prognostic marker for cancer diagnosis. Very recently, it
      has been highlighted that the serine/threonine kinase Akt plays a fundamental
      role in survival pathways and is also involved in the onset of resistance to anti
      neoplastic drugs and ionizing radiation in cell lines derived from solid tumors.
      For its full activation Akt needs to be phosphorylated on Serine 473 residue.
      Molecules that are fundamental in determining resistance to therapeutic
      treatments might serve in the future as clinical markers to tailor therapy and/or
      predict treatment response. The aim of this study was to ascertain whether or not
      flow cytometric analysis of total Akt and of its form phosphorylated on Serine
      473 could be related to standard techniques such as Western blotting with
      phosphospecific antibodies and in vitro kinase assay. To this end, we employed as
      experimental models HL-60 and PC-12 lines in which there is an enhancement of Akt
      activity. Our results showed that flow cytometry analysis, performed on fixed and
      permeabilized cells, correlated well with the results provided by in vitro
      activity assays and Western blots. Therefore, our findings might indicate that
      flow cytometric study of Akt (both total and phosphorylated) content may be
      applied in routine work for phenotyping of hematological and non-hematological
      neoplasias, and allow for its use as a useful marker for the classification and
      the prognosis of neoplastic diseases.

PMID- 12210738
TI  - Sp1 and Sp3 activate the testis-specific histone H1t promoter through the H1t/GC
      box.
AB  - The testis-specific linker histone H1t gene is transcribed exclusively in mid to
      late pachytene primary spermatocytes. Tissue specific expression of the gene is
      mediated in large part through elements located within the proximal promoter.
      Previous work in transgenic animals showed that a unique 40 bp promoter element
      designated H1t/TE is essential for spermatocyte-specific expression. The H1t/TE
      element contains a GC-box, which is a perfect consensus binding site for members
      of the Sp family of transcription factors. We have shown that Sp1 and Sp3 are
      present in testis cells from 9-day-old and adult rats and in pachytene primary
      spermatocytes and early spermatids and that they can bind to the H1t/GC-box.
      Mutagenesis of the GC-box reduced H1t promoter activity. Furthermore, a CpG
      dinucleotide within the GC-box was totally unmethylated in rat testis primary
      spermatocytes where the gene is transcribed but it was methylated in liver where
      the gene is silenced. These previous studies supported the importance of the GC
      box and suggested that Sp transcription factors contribute to expression of the
      H1t gene. In this study, we show that co-transfection of Sp1 and Sp3 expression
      vectors leads to an upregulation of histone H1t promoter activity in several cell
      lines including testis GC-2spd cells. However, very low H1t promoter activity is
      seen in GC-2spd cells grown at 39 degrees C, which correlates with lower levels
      of Sp1 and Sp3 in these cells grown at this elevated temperature. Upregulation of
      the H1t promoter by Sp1 and Sp3 was also seen in cotransfected NIH3T3 and C127I
      cell lines. On the other hand, co-transfection of the Sp1 and Sp3 expression
      vectors does not lead to upregulation of activity of the cell-cycle dependent
      histone H1d promoter.

PMID- 12210739
TI  - NG2 proteoglycan mediates beta1 integrin-independent cell adhesion and spreading
      on collagen VI.
AB  - Collagens V and VI have been previously identified as specific extracellular
      matrix (ECM) ligands for the NG2 proteoglycan. In order to study the functional
      consequences of NG2/collagen interactions, we have utilized the GD25 cell line,
      which does not express the major collagen-binding beta(1) integrin heterodimers.
      Use of these cells has allowed us to study beta(1) integrin-independent phenomena
      that are mediated by binding of NG2 to collagens V and VI. Heterologous
      expression of NG2 in the GD25 line endows these cells with the capability of
      attaching to surfaces coated with collagens V and VI. The specificity of this
      effect is emphasized by the failure of NG2-positive GD25 cells to attach to other
      collagens or to laminin-1. More importantly, NG2-positive GD25 cells spread
      extensively on collagen VI. beta(1) integrin-independent extension of ruffling
      lamellipodia demonstrates that engagement of NG2 by the collagen VI substratum
      triggers signaling events that lead to rearrangement of the actin cytoskeleton.
      In contrast, even though collagens V and VI each bind to the central segment of
      the NG2 ectodomain, collagen V engagement of NG2 does not trigger cell spreading.
      The distinct morphological consequences of NG2/collagen VI and NG2/collagen V
      interaction indicate that closely-related ECM ligands for NG2 differ in their
      ability to initiate transmembrane signaling via engagement of the proteoglycan.

PMID- 12210740
TI  - Expression of a releasable form of annexin II by human keratinocytes.
AB  - Annexin II is a multifunctional calcium-dependent phospholipid binding protein
      whose presence in epidermis has previously been reported. However, like other
      members of annexin family, annexin II has been regarded as either an
      intracellular protein or associated with the cellular membrane. Here, we report
      the presence of a releasable annexin II and p11, two monomers of annexin II
      tetramer, in keratinocyte-conditioned medium (KCM). Proteins present in KCM were
      fractionated on a gel filtration column and following further evaluation, a
      releasable protein with apparent MW of 36 kDa was identified. Further
      characterization identified this protein as the p36 monomer of annexin II
      tetramer. The phospho-tyrosine antibody did not visualize this protein as the
      phosphorylated form of p36. Several experiments were conducted to examine whether
      this protein is soluble or associated with keratinocyte cell membranes in the
      conditioned medium. A centrifugation of conditioned medium was not able to bring
      this protein down into the pellet. Surprisingly, the results of Western analysis
      identified p36 and p11, two monomers of the annexin II tetramer, in conditioned
      medium derived from either keratinocytes cultured alone or keratinocytes co
      cultured with fibroblasts. In contrast to the keratinocyte-conditioned medium in
      which annexin II was easily detectable, both monomers were barely detectable in
      conditioned medium collected from dermal fibroblasts. This finding was in
      contrast to the cell lysates in which p36 was detectable in both keratinocytes
      and fibroblasts. However, the amount of this protein was markedly higher in
      keratinocyte lysate relative to that of dermal fibroblasts. Conditioned medium
      derived from keratinocyte established from adult showed a higher level of annexin
      II compared to that of keratinocytes established from newborn babies. The
      expression of p11 seems to increase with differentiation of keratinocytes derived
      from either adult or newborn skin samples. When the site of annexin synthesis in
      human skin was examined by immunohistochemical staining, the antibody for p36
      localized the annexin to the keratinocyte cell members in the basal and
      suprabasal keratinocytes. In conclusion, Western blot detection of both p36 and
      p11 in conditioned medium from skin cells revealed that human keratinocytes, but
      not fibroblasts, express a releasable monomer form of annexin II which is
      regulated by differentiation status of keratinocytes. This finding is consistent
      with the localization of annexin II detected by immunohistochemical staining.

PMID- 12210741
TI  - MT1-MMP, but not secreted MMPs, influences the migration of human microvascular
      endothelial cells in 3-dimensional collagen gels.
AB  - Matrix metalloproteinases (MMPs) and their specific inhibitors the TIMPs play
      significant roles in angiogenesis. We investigated how the expression of specific
      MMPs and TIMPs by human microvascular endothelial cells (hmECs) was modulated by
      culture of the cells in 3-dimensional (3D) type I collagen gels versus 2
      dimensional (2D) collagen-coated surfaces. By reverse-transcription polymerase
      chain reaction (RT-PCR), levels of mRNA for MMPs-1, -2, and -13, MT1-MMP, and
      TIMPs-1 and -2 were similar in 2D versus 3D cultures. By Western blot assay, TIMP
      1 and proMMP-1 were present and were expressed similarly in media from 2D versus
      3D cultures, whereas active MMPs-1, -9, and -13 were not detected. Active MMP-13
      was present in cell lysates (CL) and was increased in lysates from 3D cultures
      relative to 2D cultures. Relative to 2D cultures, CL and media from 3D cultures
      exhibited a decrease in expression of TIMP-2 and an increased conversion of
      proMMP-2 and proMT1-MMP to active or processed forms. The MMP inhibitor GM6001
      interfered with the migration of hmECs in 3D cultures, but not in 2D cultures.
      Addition of active MMP-1 or blocking antibodies to TIMP-1 did not affect the
      migration of hmECs in 3D collagen. Migration in 3D collagen was decreased by TIMP
      2 (an inhibitor of MT1-MMP), but not by TIMP-1 (a poor inhibitor of MT1-MMP, but
      an efficient inhibitor of MMP-2). Collectively, our data indicate that MT1-MMP
      contributes significantly to the movement of hmECs through 3D collagen, in
      contrast to secretory-type MMPs-1, -2, -9, and -13, which are not critical for
      this movement.

PMID- 12210742
TI  - Synergistic stimulation of MUC1 expression in normal breast epithelia and breast
      cancer cells by interferon-gamma and tumor necrosis factor-alpha.
AB  - The MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in
      human breast cancers. Persistent stimulation by proinflammatory cytokines may
      contribute to increased MUC1 transcription by tumor cells. We demonstrate that
      MUC1 expression in T47D breast cancer cells and normal human mammary epithelial
      cells (HMEC) is enhanced by tumor necrosis factor-alpha (TNF-alpha) in the
      presence of interferon-gamma (IFN-gamma). MUC1 responsiveness to these cytokines
      was modest in T47D cells and robustly induced in HMEC. Transient transfection of
      T47D cells with mutant MUC1 promoter constructs revealed that a kappaB site at 
      589/-580 and the STAT-binding element at -503/-495 and were required for
      cooperative stimulation by TNFalpha and IFN-gamma. Binding of NFkappaB p65 to the
      MUC1 kappaB site was induced by TNF-alpha treatment, as demonstrated by
      electrophoretic mobility shift assay. Specific mutation of the kappaB site
      prevented binding of NFkappaB p65 and blocked TNF-alpha stimulation of MUC1
      promoter activity. Collectively, these studies demonstrate synergistic
      stimulation of MUC1 expression by TNF-alpha and IFN-gamma that is mediated by
      independent actions of NFkappaB p65 and STAT1alpha upon kappaB and STAT sites,
      respectively, in the MUC1 promoter. Strong induction of MUC1 expression by these
      proinflammatory cytokines is clearly evident in normal mammary epithelium. In
      contrast, breast tumor cells appear to override normal regulatory responses via
      as yet undefined cis-elements.

PMID- 12210743
TI  - Involvement of PI3-kinase and its association with c-Src in PTH-stimulated rat
      enterocytes.
AB  - Phosphoinositide-3-kinase (PI3K) is a lipid kinase, which phosphorylates the D3
      position of phosphoinositides, and is known to be activated by a host of protein
      tyrosine kinases. PI3K plays an important role in mitogenesis in several cell
      systems. However, whether parathyroid hormone (PTH) affects the activity and
      functional roles of PI3K in intestinal cells remain to be determined. The
      objective of this study was to identify and characterize the PI3K pathway, and
      its relation to other non-receptor tyrosine kinases in mediating PTH signal
      transduction in rat enterocytes. PTH dose- and time-dependently increased PI3K
      activity with a peak occurring at 2 min. The tyrosine kinase inhibitor genistein,
      c-Src inhibitor PP1 and two structurally different inhibitors of PI3K, LY294002
      and wortmannin, suppressed PI3K activity dependent on PTH. Co-immunoprecipitation
      analysis showed a constitutive association between c-Src and PI3K, which was
      enhanced by PTH treatment, suggesting that the cytosolic tyrosine kinase forms an
      immunocomplex with PI3K probably via the N-SH2 domain of the p85alpha regulatory
      subunit. In response to PTH, tyrosine phosphorylation of p85alpha was enhanced,
      effect that was abolished by PP1, the inhibitor of c-Src kinase. PTH causes a
      rapid (0.5-5 min) phosphorylation of Akt/PKB, effect that was abrogated by PI3K
      inhibitors, indicating that in rat enterocytes, PI3K is an upstream mediator of
      Akt/PKB activation by PTH. We report here that PI3K is also required for PTH
      activation of the mitogen-activated protein kinases ERK1 and ERK2. Taken
      together, the present study demonstrate, for the first time, that PTH rapidly and
      transiently stimulates PI3K activity and its down effector Akt/PKB in rat
      enterocytes playing c-Src kinase a central role in PTH-dependent PI3K activation
      and that PI3K signaling pathway contributes to PTH-mediated MAPK activation.

PMID- 12210744
TI  - Oleic acid-induced PKC isozyme translocation in RAW 264.7 macrophages.
AB  - Fatty acids are important second messengers that mediate various cellular
      functions, but their role in the formation of macrophage foam cells is not known.
      High plasma levels of oleic acid (OA) in obese patients are often associated with
      a high risk for atherosclerosis. In this study, we investigated the protein
      kinase C (PKC) isozymes involved in OA-induced lipid accumulation in RAW 264.7
      macrophages. The results show that OA induces translocation of PKC alpha, beta1,
      and delta from the cytosol to the cell membrane 5 min after the treatment. After
      16 h incubation with OA, PKC delta was found to be colocalized with adipose
      differentiation-related protein (ADRP) on the surface of lipid droplets, but
      immunoprecipitation experiments showed that PKC delta was not biochemically
      associated with ADRP. After 16 h incubation with OA plus phorbol 12-myristate 13
      acetate (PMA), PKC delta staining on the lipid droplet surface was not seen,
      whereas the accumulation of lipid droplets was unaffected. Furthermore,
      downregulation of PKC delta was confirmed by immunoblotting. These results
      demonstrate possible involvement of specific PKC isozymes in the early phase of
      lipid accumulation, possibly during the uptake of OA.

PMID- 12210745
TI  - A novel mechanism for the regulation of osteoblast differentiation: transcription
      of periostin, a member of the fasciclin I family, is regulated by the bHLH
      transcription factor, twist.
AB  - Periostin is a secreted protein that is highly expressed in early osteoblastic
      cells in vitro and in periosteum and periodontal ligament tissues in vivo. It is
      known that periostin supports cellular adhesion and spreading in vitro. Although,
      the mechanisms of transcriptional regulation of periostin are poorly understood,
      gene-profiling data have revealed that overexpression of Twist, a basic helix
      loop-helix (bHLH) transcription factor, resulted in increased periostin
      expression as validated by Northern blot and reverse transcription-polymerase
      chain reaction (RT-PCR) analyses. Twist is an important transcription factor for
      cell type determination and differentiation and has been shown to play an
      important regulatory role in early osteogenesis. In situ hybridization of mouse
      calvarial bones indicated that periostin and Twist mRNA are co-localized at the
      osteogenic fronts of calvarial bones. To characterize the 5' flanking region of
      the periostin gene, primer extension was carried out to identify the
      transcription start site, and DNA sequence analysis confirmed the presence of a
      'Twist-box' response element. The results of electrophoretic mobility shift assay
      (EMSA) using nuclear extracts of MC3T3-E1 cells revealed that Twist bound to the
      Twist-box sequence on the periostin promoter. In vivo footprinting experiments
      using ligation-mediated PCR (LM-PCR) indicated that the Twist-box sequence was
      protected in undifferentiated MC3T3-E1 preosteoblasts but not in differentiated
      MC3T3-E1 osteoblasts. To determine whether Twist actually regulates the periostin
      expression, 293T cells were transiently co-transfected with the periostin
      promoter construct and the human Twist expression vector. Reporter analysis
      indicated that the periostin promoter activities were enhanced by overexpression
      of Twist. These data suggest that Twist can bind to the periostin promoter in
      undifferentiated preosteoblasts and up-regulate periostin expression, consistent
      with the up-regulation of periostin expression by Twist as observed in the gene
      profiling data.

PMID- 12210746
TI  - Biochemical and cellular characteristics of the four splice variants of protein
      kinase CK1alpha from zebrafish (Danio rerio).
AB  - Protein kinase CK1 (previously known as casein kinase I) conforms to a subgroup
      of the great protein kinase family found in eukaryotic organisms. The CK1
      subgroup of vertebrates contains seven members known as alpha, beta, gamma1,
      gamma2, gamma3, delta, and epsilon. The CK1alpha gene can generate four variants
      (CK1alpha, CK1alphaS, CK1alphaL, and CK1alphaLS) through alternate splicing,
      characterized by the presence or absence of two additional coding sequences. Exon
      "L" encodes a 28-amino acid stretch that is inserted after lysine 152, in the
      center of the catalytic domain. The "S" insert encodes 12 amino acid residues and
      is located close to the carboxyl terminus of the protein. This work reports some
      biochemical and cellular properties of the four CK1alpha variants found to be
      expressed in zebrafish (Danio rerio). The results obtained indicate that the
      presence of the "L" insert affects several biochemical properties of CK1alpha:
      (a) it increases the apparent Km for ATP twofold, from approximately 30 to
      approximately 60 microM; (b) it decreases the sensitivity to the CKI-7 inhibitor,
      raising the I50 values from 113 to approximately 230 microM; (c) it greatly
      decreases the heat stability of the enzyme at 40 degrees C. In addition, the
      insertion of the "L" fragment exerts very important effects on some cellular
      properties of the enzyme. CK1alphaL concentrates in the cell nucleus, excluding
      nucleoli, while the CK1alpha variant is predominantly cytoplasmic, although some
      presence is observed in the nucleus. This finding supports the thesis that the
      basic-rich region found in the "L" insert acts as a nuclear localization signal.
      The "L" insert-containing variant was also found to be more rapidly degraded
      (half-life of 100 min) than the CK1alpha variant (half-life of 400 min) in
      transfected Cos-7 cells.

PMID- 12210747
TI  - ATP and UTP at low concentrations strongly inhibit bone formation by osteoblasts:
      a novel role for the P2Y2 receptor in bone remodeling.
AB  - There is increasing evidence that extracellular nucleotides act on bone cells via
      multiple P2 receptors. The naturally-occurring ligand ATP is a potent agonist at
      all receptor subtypes, whereas ADP and UTP only act at specific receptor
      subtypes. We have reported that the formation and resorptive activity of rodent
      osteoclasts are stimulated powerfully by both extracellular ATP and its first
      degradation product, ADP, the latter acting at nanomolar concentrations, probably
      via the P2Y1 receptor subtype. In the present study, we investigated the actions
      of ATP, ADP, adenosine, and UTP on osteoblastic function. In 16-21 day cultures
      of primary rat calvarial osteoblasts, ADP and the selective P2Y1 agonist 2
      methylthioADP were without effect on bone nodule formation at concentrations
      between 1 and 125 microM, as was adenosine. However, UTP, a P2Y2 and P2Y4
      receptor agonist, known to be without effect on osteoclast function, strongly
      inhibited bone nodule formation at concentrations >or= 1 microM. ATP was
      inhibitory at >or= 10 microM. Rat osteoblasts express P2Y2, but not P2Y4 receptor
      mRNA, as determined by in situ hybridization. Thus, the low-dose effects of
      extracellular nucleotides on bone formation and bone resorption appear to be
      mediated via different P2Y receptor subtypes: ADP, signalling through the P2Y1
      receptor on both osteoclasts and osteoblasts, is a powerful stimulator of
      osteoclast formation and activity, whereas UTP, signalling via the P2Y2 receptor
      on osteoblasts, blocks bone formation by osteoblasts. ATP, the 'universal'
      agonist, can simultaneously stimulate resorption and inhibit bone formation.
      These findings suggest that extracellular nucleotides could function locally as
      important negative modulators of bone metabolism, perhaps contributing to bone
      loss in a number of pathological states.

PMID- 12210748
TI  - P-cadherin expression in canine lactating mammary gland.

PMID- 12210749
TI  - Analysis of the energetic state of heart cells after adenovirus-mediated
      expression of hALC-1.
AB  - Expression of the human atrial myosin light chain 1 (hALC-1) in the cardiac
      ventricle in vivo as well as in primary cultivated adult cardiomyocytes caused a
      pronounced positive inotropic effect. Therefore, it is one of the most promising
      candidate gene to treat congestive heart failure (CHF). In this work, we
      investigated, whether hALC-1 expression also modifies the energetic state of
      cardiomyocytes. Primary cultivated neonatal rat hearts cells (NRHC) were infected
      with adenoviral vectors (Ad vectors) containing a hALC-1 cDNA (AdCMV.hALC-1) or a
      control Ad vector. Infection efficiency of NRHC reached 100% at 50 multiplicity
      of infection (MOI). Interestingly and in contrast to primary cultures of liver
      cells, there were no cytotoxic side effects or induction of apoptosis up to MOI
      50 in Ad vector infected NRHC. NRHC expressed large amounts of hALC-1 upon
      infection with AdCMV.hALC-1 which could easily been detected by protein staining
      and Western blot analysis. Analysis of intracellular hALC-1 localization by
      double-labeling immunofluorescence of AdCMV.hALC-1 infected cardiomyocytes
      revealed the typical myofibrillar striation pattern, as well as co-localization
      of hALC-1 with myosin heavy chains. There was no difference in the oxygen
      consumption between controls and AdCMV.hALC-1 infected NRHC. These data suggest
      that first: adenoviral vectors could be used as a safe and effective tool for
      gene transfer to cardiomyocytes, and second: that a positive inotropic effect of
      hALC-1 is not associated with enhanced oxygen consumption.

PMID- 12210750
TI  - Immunocytochemical studies on lipid droplet-surface proteins in adrenal cells.
AB  - Perilipin and ADRP, located on the surface of intracellular lipid droplets, are
      proposed to be involved in adipocyte lipid metabolism. The aim of the present
      study was to investigate the effect of PKA and PKC activities on the distribution
      of perilipin and ADRP in primary cultured adrenal cells, and the role of ERK in
      PMA- and calphostin C-induced steroidogenesis. Immunofluorescence staining
      indicated that in addition to p160, a capsular protein of steroidogenic lipid
      droplets, perilipin and ADRP were localized on the lipid droplet surface. Stimuli
      such as activation of PKA by db cAMP or inhibition of PKC by calphostin C, which
      increase corticosterone synthesis in various magnitudes, caused detachment of
      p160 and perilipin, but not ADRP, from the lipid droplet surface. Activation of
      PKC by PMA induced increase in corticosterone synthesis, however, it did not
      affect the distribution of perilipin, p160, or ADRP on the lipid droplet surface,
      suggesting the presence of mechanisms for promoting sterodiogensis other than
      causing detachment of lipid droplet surface proteins. We further demonstrated
      that ERK pathway was involved in PMA-induced steroidogenesis, since PD98059,
      specific inhibitor of MEK, blocked the increases in steroidogenesis and
      phosphorylation of ERK caused by PMA, but not by cAMP-PKA. These data indicate
      that p160, perilipin, and ADRP were all located on the lipid droplet surface in
      rat adrenal cells. On the basis of its non-responsiveness to lipolytic
      stimulation, ADRP may be a structural protein of the lipid droplet surface,
      whereas their immediate response to lipolytic stimuli suggest that perilipin and
      p160 are functional proteins. PKC regulates adrenal steroidogenesis through ERK
      cascade, whereas PKA pathway does not involve ERK.

PMID- 12210751
TI  - Differentiation-dependent induction of CYP1A1 in cultured rat small intestinal
      epithelial cells, colonocytes, and human colon carcinoma cells: basement membrane
      mediated apoptosis.
AB  - Rat small intestinal epithelial cells and human colon adenocarcinoma cells
      cultured on Matrigel expressed the differentiation specific enzyme, sucrase
      isomaltase, as determined by indirect immunofluorescence. Rat small intestinal
      epithelial cells, rat colonocytes, and human colon adenocarcinoma cells developed
      an altered morphology when cultured on Matrigel and became apoptotic within 24-48
      h. Benzo[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin caused a 2- and 5-fold
      induction, respectively, of ethoxyresorufin-o-deethylase activity in rat small
      intestinal epithelial cells cultured on Matrigel. Benzo[a]pyrene- or 2,3,7,8
      tetrachlorodibenzo-p-dioxin-induced ethoxyresorufin-o-deethylase activity in rat
      small intestinal epithelial cells cultured on plastic was not detected. 2,3,7,8
      tetrachlorodibenzo-p-dioxin treatment caused a 14-fold induction of transfected,
      rat CYP1A1-promoter-luciferase activity in rat small intestinal epithelial cells
      cultured on Matrigel. Benzo[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin
      treatment induced ethoxyresorufin-o-deethylase activity by 6- and 1.6-fold,
      respectively in rat colonocytes cultured on Matrigel. Induction of
      ethoxyresorufin-o-deethylase activity was not observed in rat colonocytes
      cultured on plastic. CYP1A1-promoter-luciferase activity was induced 3-fold by
      2,3,7,8-tetrachlorodibenzo-p-dioxin in rat colonocytes cultured on Matrigel.
      Induction of CYP1A1-promoter-luciferase activity in rat small intestinal
      epithelial cells or rat colonocytes cultured on plastic was not observed.
      Ethoxyresorufin-o-deethylase activity in human colon adenocarcinoma cells,
      cultured on either plastic or Matrigel, was induced 7-fold by benzo[a]pyrene.
      2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced ethoxyresorufin-o-deethylase activity
      was 2-fold greater in human colon adenocarcinoma cells cultured on Matrigel
      compared to cells cultured on plastic. Extracellular matrix-mediated
      differentiation and apoptosis of intestinal cells provide in vitro systems for
      study of the regulation of CYP1A1 expression, carcinogen activation in the gut
      and mechanism(s) of apoptosis of colon cancer cells.

PMID- 12210752
TI  - Reversible changes in the nuclear lamina induced by hyperthermia.
AB  - The nuclear matrix (NM) has been identified as a potential target for heat
      induced cell killing. Previous studies have shown that heat-shock may
      significantly modulate lamin B content. Since changes in NM structure have often
      been accompanied by changes in protein composition, we investigated whether
      hyperthermia induced changes in nuclear lamina (NL) structure in non-tolerant and
      thermotolerant cells, and the implications of these changes on cell survival.
      Using indirect immunofluorescence techniques and confocal microscopy, we found
      that heating cells at 42 or 45.5 degrees C caused invaginations and other
      distortions of the peripheral NL. While hyperthermia did not alter the number or
      structure of internal lamin B foci, heat-induced alterations to the peripheral NL
      were dose-dependent. Interestingly, NL structure recovered with time after
      heating in cells that were destined to live or die. Thermotolerant cells heated
      at 45.5 degrees C showed similar initial changes in the NL compared to non
      tolerant cells, but recovery occurred much faster. Taken together, these results
      suggest that the amount of initial damage to the peripheral NL is not correlated
      with heat-induced cell killing. However, the possibility that an increased rate
      of recovery might confer a survival advantage cannot be discounted.

PMID- 12210753
TI  - Systemically administered rhBMP-2 promotes MSC activity and reverses bone and
      cartilage loss in osteopenic mice.
AB  - Osteoporosis is a disease manifested in drastic bone loss resulting in osteopenia
      and high risk for fractures. This disease is generally divided into two subtypes.
      The first, post-menopausal (type I) osteoporosis, is primarily related to
      estrogen deficiency. The second, senile (type II) osteoporosis, is mostly related
      to aging. Decreased bone formation, as well as increased bone resorption and
      turnover, are thought to play roles in the pathophysiology of both types of
      osteoporosis. In this study, we demonstrate in murine models for both type I
      (estrogen deficiency) and type II (senile) osteopenia/osteoporosis that reduced
      bone formation is related to a decrease in adult mesenchymal stem cell (AMSC)
      number, osteogenic activity, and proliferation. Decreased proliferation is
      coupled with increased apoptosis in AMSC cultures obtained from osteopenic mice.
      Recombinant human bone morphogenetic protein (rhBMP-2) is a highly osteoinductive
      protein, promoting osteogenic differentiation of AMSCs. Systemic intra-peritoneal
      (i.p.) injections of rhBMP-2 into osteopenic mice were able to reverse this
      phenotype in the bones of these animals. Moreover, this change in bone mass was
      coupled to an increase in AMSCs numbers, osteogenic activity, and proliferation
      as well as a decrease in apoptosis. Bone formation activity was increased as
      well. However, the magnitude of this response to rhBMP-2 varied among different
      stains of mice. In old osteopenic BALB/c male mice (type II osteoporosis model),
      rhBMP-2 systemic treatment also restored both articular and epiphyseal cartilage
      width to the levels seen in young mice. In summary, our study shows that AMSCs
      are a good target for systemically active anabolic compounds like rhBMP-2.

PMID- 12210754
TI  - Transport of inorganic phosphate in primary cultures of chondrocytes isolated
      from the tibial growth plate of normal adolescent chickens.
AB  - This report describes Pi transport activity in chondrocytes isolated from the
      growth plate (GP) of normal adolescent chickens grown in primary cell culture.
      Our recent work showed that Pi transport in matrix vesicles (MV) isolated from
      normal GP cartilage was not strictly Na+-dependent, whereas previously
      characterized Pi transport from rachitic GP cartilage MV was. This Na+-dependent
      Pi transporter (NaPiT), a member of the Type III Glvr-1 gene family, is expressed
      only transiently during early differentiation of GP cartilage, is enhanced by Pi
      deficiency, and is most active at pH 6.8. Since GP mineralization requires
      abundant Pi and occurs under slightly alkaline conditions, it seemed unlikely
      that this type of Pi transporter was solely responsible for Pi uptake during
      normal GP development. Therefore we asked whether the lack of strict Na+
      dependency in Pi transport seen in normal MV was also evident in normal GP
      chondrocytes. In fact, cellular Pi transport was found not to be strictly Na+
      dependent, except for a brief period early in the culture. Choline could equally
      serve as a Na+ substitute. Activity of choline-supported Pi transport was optimum
      at pH 7.6-8.0. In addition, prior exposure of the cells to elevated extracellular
      Pi (2-3 mM) strongly enhanced subsequent Pi uptake, which appeared to depend on
      prior loading of the cells with mineral ions. Prevention of Pi loading by
      pretreatment with Pi transport inhibitors not only inhibited subsequent cellular
      Pi uptake, it also blocked mineral formation. Treatment with elevated
      extracellular Pi did not induce apoptosis in these GP chondrocytes.

PMID- 12210755
TI  - Microwave exposure induces Hsp70 and confers protection against hypoxia in chick
      embryos.
AB  - To determine if microwave exposure could elicit a biological effect in the
      absence of thermal stress, studies were designed in which chick embryos were
      exposed to athermal microwave radiation (915 MHz) to look for induction of Hsp70,
      a protein produced during times of cellular stress that aids in the protection of
      cellular components. Levels of Hsp70 were found to increase within 2 h, with
      maximum expression ( approximately 30% higher than controls) typically occurring
      by 3 h from the start of exposure. Other embryos were exposed to microwave
      radiation prior to being subjected to hypoxic stress, and were found to have
      significantly higher survival (P < 0.05) following re-oxygenation than non
      exposed controls. The results of these studies indicate that not only can
      athermal microwave exposures activate the stress protein response pathway; they
      can also enhance survivability following exposure to a subsequent, potentially
      lethal stress. From a public health standpoint, it is important that more studies
      be performed to determine if repeated exposures, a condition likely to be found
      in cell phone use, are still beneficial.

PMID- 12210756
TI  - 1,25(OH)2D3-mediated phosphate uptake in isolated chick intestinal cells: effect
      of 24,25(OH)2D3, signal transduction activators, and age.
AB  - We have previously reported an absence of a 1,25(OH)2D3-mediated effect on 45Ca
      handling by intestinal epithelial cells isolated from normal chicks (Nemere and
      Campbell [2000] Steroids 65:451-457). In the current work, we provide evidence
      that in similar cell preparations, 1,25(OH)2D3 increased 32P uptake within 5 min
      of addition, and reached 150% of controls after 10 min (P < 0.05). Both isolated
      enterocytes and the perfused duodenal loop system exhibited apparent biphasic
      dose-response curves for 1,25(OH)2D3-stimulated 32P uptake and transport, and
      inhibition of stimulation by 24,25(OH)2D3. A comparison of signal transduction
      activators demonstrated the following parallels in both isolated intestinal cells
      and perfused duodena: lack of effect of forskolin (a protein kinase (PK) A
      activator) on 32P handling, but simulation by BAY K8644 (a calcium channel
      activator) and phorbol ester (a PKC activator). Finally, we tested the effect of
      1,25(OH)2D3 on phosphate uptake in epithelial cells isolated from birds of
      increasing ages (7, 14, and 28 wk). In contrast to the robust response of cells
      from young, growing chicks, 1,25(OH)2D3 had no effect on enterocytes from 14 or
      28 wk birds. Western analyses with Ab 099 against the 1,25(OH)2D3 (1,25D3)
      Membrane-Associated Rapid Response Steroid (MARRS) binding protein revealed a
      decrease in average density of the immunoreactive band with age. PKC activity
      determined in isolated epithelial cells exhibited a decrease in average basal
      (control) activity with age, as well as a decrease in response to 1,25(OH)2D3
      activation. In enterocytes from 7-14- or 28-week birds, PKC was enhanced 170,
      120, and 105% of controls, respectively. The combined data validate 32P uptake in
      isolated enterocytes as a model system to study 1,25D3-MARRS protein function,
      and indicate that for phosphate transport, the rapid actions of 1,25(OH)2D3 are
      physiologically more important in growing animals than immature ones.

PMID- 12210757
TI  - Altered expression and localization of N-myristoyltransferase in experimentally
      induced rat model of ischemia-reperfusion.
AB  - N-myristoyltransferase (NMT) catalyzes the attachment of myristate onto the amino
      terminal glycine residue of select polypeptides. In the present study, we
      investigated the expression and activity of NMT in rat heart after ischemia and
      reperfusion. Western blot analysis of rat heart samples indicated a prominent
      immunoreactive band of 66 kDa probed with human NMT antibody. Both the expression
      and activity of NMT were increased by ischemia-reperfusion. Immunohistochemical
      studies showed cytosolic localization of NMT in normal rat heart and predominant
      nuclear localization after ischemia followed by reperfusion. The pre-ischemic
      perfusion and post-ischemic reperfusion of hearts with a cell-permeable calpain
      inhibitor (N-Ac-Leu-Leu-methioninal) suppressed the increase in calpain
      expression and reversed the localization of NMT from nucleus to cytoplasm. This
      is the first study demonstrating the expression and alteration of NMT
      localization in cardiac ischemia and pertaining to a possible role of co
      translational modification of proteins in cardiac functions and injury.

PMID- 12210758
TI  - Role of endogenous regucalcin in transgenic rats: suppression of kidney cortex
      cytosolic protein phosphatase activity and enhancement of heart muscle microsomal
      Ca2+-ATPase activity.
AB  - Rats were generated by pronuclear injection of the transgene with a cDNA
      construct encoding rat regucalcin that is a regulatory protein of Ca2+ signaling.
      Transgenic (TG) founders were fertile, transmitted the transgene at the expected
      frequency, and bred to homozygote. Western analysis of the cytosol prepared from
      the tissue of TG female rats (5-week-old) showed a remarkable expression of
      regucalcin (3.3 kDa) protein in the liver, kidney cortex, heart, lung, stomach,
      brain, spleen, muscle, colon, and duodenum. Regucalcin expression of TG male rats
      was seen in the liver, kidney cortex, heart, and lung. In wild-type (wt) male and
      female rats, regucalcin was mainly present in the liver and kidney cortex.
      Regucalcin inhibited protein phosphatase activity in rat kidney cortex cytosol
      and activated Ca2+-ATPase activity in rat heart muscle microsomes. The
      suppressive effect of regucalcin on protein phosphatase activity was
      significantly enhanced in the cytosol of kidney cortex of TG male and female rats
      as compared with those of wt rats. Likewise, heart muscle microsomal Ca2+-ATPase
      activity was significantly enhanced in TG rats. The changes in their enzyme's
      activities in TG rats were completely abolished in the presence of anti
      regucalcin monoclonal antibody (100 ng/ml) in the enzyme reaction mixture.
      Moreover, the body weight of TG female rats was significantly lowered as compared
      with that of wt rats. Serum inorganic phosphorus concentration was significantly
      increased in TG male and female rats, while serum calcium, glucose, triglyceride,
      free cholesterol, albumin, and urea nitrogen concentrations were not
      significantly altered in TG rats. Regucalcin TG rats should be a useful model to
      define a regulatory role of endogenous regucalcin in the tissues in vivo.

PMID- 12210759
TI  - Effects of alpha lipoic acid, ascorbic acid-6-palmitate, and fish oil on the
      glutathione, malonaldehyde, and fatty acids levels in erythrocytes of
      streptozotocin induced diabetic male rats.
AB  - In this research, it has been aimed to evaluate the improvement effects of alpha
      lipoic acid (ALA), ascorbic acid-6-palmitate (AA6P), fish oil (FO), and their
      combination (COM) on some biochemical properties in erythrocytes of
      streptozotocin (STZ)-induced diabetic male rats. According to experimental
      results, glutathione (GSH) level in erythrocytes decreased in diabetes (P <
      0.01), D + ALA, and D + AA6P groups (P < 0.001). Malonaldehyde (MA) level
      increased in diabetes (P < 0.05), D + FO, and D + COM groups (P < 0.001), but its
      level in D + AA6P and D + ALA groups was lower in diabetes group (P < 0.01).
      Total lipid level in diabetes and diabetes plus antioxidant administered groups
      were higher than control. Total cholesterol level was high in diabetes and D +
      ALA groups (P < 0.05), but its level reduced in D + FO compared to control and
      diabetes groups, P < 0.05, < 0.001, respectively. Total triglyceride (TTG) level
      was high in the D + ALA (P < 0.05) and D + COM (P < 0.001) groups. In contrast,
      TTG level in blood of diabetes group was higher than diabetes plus antioxidant
      and FO administered groups (P < 0.001). According to gas chromatography analysis
      results, while the palmitic acid raised in diabetes group (P < 0.05), stearic
      acid in D + FO, D + ALA, and diabetes groups was lower than control (P < 0.05),
      oleic acid reduced in D + COM and D + FO groups, but its level raised in D + AA6P
      and D + ALA groups (P < 0.01). As the linoleic acid (LA) elevated in ALA + D, D +
      AA6P, and diabetes groups, linolenic acid level in diabetes, D + AA6P, and D + FO
      groups was lower than control (P < 0.001). Arachidonic acid (AA) decreased in D +
      ALA, D+ AA6P, and diabetes groups (P < 0.01), but its level in D + COM and D + FO
      was higher than control (P < 0.05). Docosahexaenoic acid (DHA) increased in D +
      AA6P and D + COM (P < 0.05). While the total saturated fatty acid level raised in
      diabetes group, its level reduced in D + ALA and D + FO groups (P < 0.05). In
      contrast, total unsaturated fatty acid level in D + ALA and D + FO groups was
      higher than control (P < 0.05). In conclusion, present data have confirmed that
      the combination of the ALA, AA6P, and FO have improvement effects on the
      recycling of GSSG to reduced GSH in erythrocytes of diabetic rats, and in
      addition to this, oxidative stress was suppressed by ALA and AA6P, and
      unsaturated fatty acid degree was raised by the effects of ALA and FO.

PMID- 12210761
TI  - Role of nuclear PKC delta in mediating caspase-3-upregulation in Jurkat T
      leukemic cells exposed to ionizing radiation.
AB  - The response of Jurkat T cells to ionizing radiation (IR) includes cell cycle
      arrest and DNA damage, which lead to the occurrence of apoptosis. Here, we try to
      elucidate some of the early intracellular signals which control the induction of
      such a process upon IR exposure, addressing to examine the specific role of
      several PKC isoforms (delta, epsilon, zeta) and their subcellular distribution.
      Attention has been focused on the connections between nuclear PKC delta
      activation and the expression of cell death regulators (Bcl-2 family proteins
      Bad, Bax and Bcl-2) and cell death effector caspase-3 (CPP32) which lead to the
      cleavage of cytoskeletal and nuclear proteins and induction of apoptosis.
      Altogether these results let us to conclude that PKC delta, potentiating the pro
      apoptotic effect of caspase 3, plays a key role in the cellular response to IR
      and thus can be considered a molecular target for therapy.

PMID- 12210760
TI  - Human endothelial cells selectively express large amounts of pancreatic-type
      ribonuclease (RNase 1).
AB  - Pyrimidine-specific ribonucleases are a superfamily of structurally related
      enzymes with distinct catalytic and biological properties. We used a combination
      of enzymatic and non-enzymatic assays to investigate the release of such enzymes
      by isolated cells in serum-free and serum-containing media. We found that human
      endothelial cells typically expressed large amounts of a pancreatic-type RNase
      that is related to, if not identical to, human pancreatic RNase. This enzyme
      exhibits pyrimidine-specific catalytic activity, with a marked preference for
      poly(C) substrate over poly(U) substrate. It was potently inhibited by placental
      RNase inhibitor, the selective pancreatic-type RNase inhibitor Inhibit-Ace, and a
      polyclonal antibody against human pancreatic RNase. The enzyme isolated from
      medium conditioned by immortalized umbilical vein endothelial cells (EA.hy926)
      possesses an amino-terminal sequence identical to that of pancreatic RNase, and
      shows molecular heterogeneity (molecular weights 18,000-26,000) due to different
      degrees of N-glycosylation. Endothelial cells from arteries, veins, and
      capillaries secreted up to 100 ng of this RNase daily per million cells, whereas
      levels were low or undetectable in media conditioned by other cell types
      examined. The corresponding messenger RNA was detected by RT-PCR in most cell
      types tested so far, and level of its expression was in keeping with the amounts
      of protein. The selective strong release of pancreatic-type RNase by endothelial
      cells suggests that it is endowed with non-digestive functions and involved in
      vascular homeostasis.

PMID- 12210762
TI  - BEACH family of proteins: phylogenetic and functional analysis of six
      Dictyostelium BEACH proteins.
AB  - The beige and Chediak-Higashi syndrome (BEACH)-domain containing proteins
      constitute a new family of proteins found in all eukaryotes. The function of
      these proteins, which include the Chediak-Higashi syndrome (CHS) protein,
      Neurobeachin, LvsA, and FAN, is still poorly understood. To understand the
      diversity of this novel protein family, we analyzed a large array of BEACH-family
      protein sequences from several organisms. Comparison of all these sequences
      suggests that they can be classified into five distinct groups that may represent
      five distinct functional classes. In Dictyostelium we identified six proteins in
      this family, named LvsA-F, that belong to four of those classes. To test the
      function of these proteins in Dictyostelium we created disruption mutants in each
      of the lvs genes. Phenotypic analyses of these mutants indicate that LvsA is
      required for cytokinesis and osmoregulation and LvsB functions in lysosomal
      traffic. The LvsC-F proteins are not required for these or other processes such
      as growth and development. These results strongly support the concept that BEACH
      proteins from different classes have distinct cellular functions. Having six
      distinct BEACH proteins, Dictyostelium should be an excellent model system to
      dissect the molecular function of this interesting family of proteins.

PMID- 12210763
TI  - Differential effects of iron deficiency on the expression of CD80 and CD86 co
      stimulatory receptors in mitogen-treated and untreated murine spleen cells.
AB  - The interaction of CD28 and its ligands (CD80, CD86) on antigen presenting cells
      and that of TCR/CD3-MHC are required for T lymphocyte activation. To determine
      whether impaired lymphocyte proliferation associated with iron deficiency is due
      to reduced expression of these ligands, spleen cells obtained from eight to nine
      C57BL/6 mice/group of iron deficient (ID), iron replete (R), control (C), pair
      fed (PF), and high iron (HI) mice were labeled with anti-CD80-fluorescein
      isothiocyante (FITC) and anti-CD86-FITC. Diets differed only in iron
      concentration: 5, 50, and 125 mg/kg for the ID, C, and HI, respectively. Mean
      levels of hemoglobin and liver iron stores of ID and R mice were less than 50%
      those of C mice (P < 0.005). In non-activated and concanavalin A-treated
      cultures, significant differences were observed among groups in the percentage of
      CD80 + cells: ID>R > C = PF = HI (P < 0.05). The same trend was observed for CD86
      + cells (P > 0.05). Fluorescence intensity (FI) of either marker did not
      significantly change by iron status. In vitro iron chelation by deferoxamine (20,
      200 microg/ml) for 1, 2, and 24 h increased FI of both markers on unactivated B
      and T cells (P < 0.05). However, it had no effect on FI of either marker of
      mitogen-treated cells presumably because the maximum levels are achieved by the
      mitogen. Lymphocyte proliferative responses to mitogens positively and
      significantly correlated with CD80 and CD86 FI (r = 0.41-0.59) but negatively
      correlated with the percentages of CD80 + cells (r = -0.48) (P < 0.05). Data
      suggest that impaired lymphocyte proliferation associated with iron deficiency is
      not due to reduced CD80 and CD86 expression.

PMID- 12210764
TI  - Evidence implicating a mid-region sequence of IGFBP-3 in its specific IGF
      independent actions.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3) is one of six high
      affinity-binding proteins that share a common function in regulating the
      bioavailability of the insulin-like growth factors. The six binding proteins have
      highly conserved C- and N-terminals that are essential to this function.
      Additionally, they all have specific functions on cellular homeostasis
      independent to the regulation of the insulin-like growth factors. It has
      previously been shown that insulin-like growth factor binding protein-3 can
      accentuate UV-induced apoptosis in a human carcinoma cell line. Using the KYSE
      190 oesophageal carcinoma cell line we have demonstrated that a 15 amino acid
      (aa) peptide that lies within the mid-region of the protein can mimic the effect
      of the intact protein. This region contains the serine residues Ser(111) and
      Ser(113). Using two protocols, we modified these serine residues and have shown
      that both phosphorylation and derivatization of IGFBP-3 can negate the
      accentuation of UV-induced cell death. These three independent pieces of evidence
      support the hypothesis that the variable mid-region is responsible for the
      specific pro-apoptotic functions of IGFBP-3, and suggest that phosphorylation may
      provide a mechanism for regulation of this action.

PMID- 12210765
TI  - Subcellular localization of the hypusine-containing eukaryotic initiation factor
      5A by immunofluorescent staining and green fluorescent protein tagging.
AB  - Eukaryotic initiation factor 5A (eIF-5A) is the only protein in nature that
      contains hypusine, an unusual amino acid residue formed posttranslationally by
      deoxyhypusine synthase and deoxyhypusine hydroxylase. Although the eIF-5A gene is
      essential for cell survival and proliferation, the precise function and
      localization of eIF-5A remain unclear. In this study, we have determined the
      subcellular distribution of eIF-5A by indirect immunofluorescent staining and by
      direct visualization of green fluorescent protein tagged eIF-5A (GFP-eIF5A).
      Immunofluorescent staining of the formaldehyde-fixed cells showed that eIF-5A was
      present in both the nucleus and cytoplasm. Only the nuclear eIF-5A was resistant
      to Triton extraction. Direct visualization of GFP tagged eIF-5A in living cells
      revealed the same whole-cell distribution pattern. However, a fusion of an
      additional pyruvate kinase (PK) moiety into GFP-eIF-5A precluded the nuclear
      localization of GFP-PK-eIF-5A fusion protein. Fusion of the GFP-PK tag with three
      different domains of eIF-5A also failed to reveal any nuclear localization of the
      fusion proteins, suggesting the absence of receptor-mediated nuclear import.
      Using interspecies heterokaryon fusion assay, we could detect the nuclear export
      of GFP-Rev, but not of GFP-eIF-5A. The whole-cell distribution pattern of eIF-5A
      was recalcitrant to the treatments that included energy depletion, heat shock,
      and inhibition of transcription, translation, polyamine synthesis, or CRM1
      dependent nuclear export. Collectively, our data indicate that eIF-5A gains
      nuclear entry via passive diffusion, but it does not undergo active
      nucleocytoplasmic shuttling.

PMID- 12210767
TI  - A new synthesis of oxadiazole, thiazolidinone, N-phthalimidoamino carbonyl and
      arylidene derivatives with potential antimicrobial activity.
AB  - Condensation of carbohydrazide derivatives Ia, b with dimethyl
      acetylenedicarboxylate and acetylenedicarboxylic acid yielded benzofuran
      derivatives II a-d. Reaction of Ib with aromatic aldehydes formed products III a
      d. Treatment of compounds III a-d with mercaptoacetic acid yielded the
      cyclocondensation products (IVa-d). Phthalic anhydride reacted with compounds
      (Ia, b)to form products (Va, b). It has been found that both khellin and visnagin
      (VIa, b)react with aromatic aldehydes to give arylidene derivatives (VIIa-e).
      Condensation of diphenyl nitrilamine with 2-arylidene furochromones VII
      derivatives afforded cyclo-adducts (VIII a-i). The antibacterial activities of
      the selected compounds were tested against Staphylococcus aureus, B. subtilis, E.
      coli, Pseudomonas, Salmonella and Erwinia with good results.

PMID- 12210768
TI  - Alkannin and shikonin: effect on free radical processes and on inflammation - a
      preliminary pharmacochemical investigation.
AB  - Alkannin and shikonin, two natural products from Alkanna tinctoria and
      Lithospermum erhythrorhizon (Boraginaceae), are used in folk medicine where they
      are claimed to possess, among other properties, wound healing and anti
      inflammatory activity. We investigated, together with the structurally related
      naphthazarin, their in vitro antioxidant and hydroxyl radical scavenging activity
      as well as their in vivo antiinflammatory activity. I was found that all examined
      compounds significantly inhibited in vitro lipid peroxidation of ra hepatic
      microsomal membranes, competed with DMSO for free hydroxyl radicals, and reduced
      inflammation (mouse paw edema induced by FCA) very efficiently. The examined
      compounds proved equal or superior to the common reference compounds for each of
      these properties. I is concluded that the claimed and/or proven actions of
      alkannin and shikonin are attributable at least partly to their intervention in
      free radical processes.

PMID- 12210769
TI  - New withanolides and other constituents from the fruit of Withania somnifera.
AB  - Two new steroidal lactones of the withanolide-type, 5beta, 6alpha, 14alpha,
      17beta, 20beta-pentahydroxy-1-oxo-20 S, 22R-witha-2, 24-dienolide (1)and 6alpha,
      7alpha-epoxy-5alpha, 14alpha, 17alpha, 23beta-tetrahydroxy-1-oxo-22R-witha-2, 24
      dienolide (2), were isolated from the fruit of Withania somnifera (L.) Dunal
      (Solanaceae) growing in Southern Egypt, together with two known coumarins,
      scopoletin (3)and aesculetin (4), a known triterpene, viz. Beta-amyrin (5), and
      two known phytosterols, viz. stigmasterol (6) and sitosterol (7). The structures
      of the isolated compounds have been elucidated by spectroscopic methods including
      UV, IR, (1)H-, (13)C-NMR, DEPT experiments, HRFAB-, FAB-, and EI-mass
      spectrometry. The in vitro antimicrobial activity of the new withanolide (1) and
      the alcoholic fruit extract are discussed.

PMID- 12210766
TI  - Differential nuclear receptor signalling from DR4-type response elements.
AB  - Nuclear receptors form a large family of highly related transcription factors
      that transform an incoming signal in the form of a lipophilic hormone into an
      activation of the basal transcriptional machinery. The specific recognition of
      nuclear receptor DNA binding sites, referred to as response elements (REs),
      determines the genes that can be regulated by nuclear hormones. In this study, it
      was shown that the complexes of the retinoid X receptor (RXR) with either the
      vitamin D3 receptor (VDR), the thyroid hormone receptor (T3R) or the liver X
      receptor (LXR) have comparable functionality on a RE of the rat pit-1 gene that
      is formed by a direct repeat of two hexameric binding motifs spaced by 4
      nucleotides (DR4). The sequence of two nucleotides 5'-flanking the downstream
      binding motif of this DR4-type RE and, interestingly, also those flanking the
      upstream motif were shown to have in part rather drastic and receptor-specific
      effects on heterodimer complex formation on DNA. In particular, a downstream
      substitution into GA reduced the complex formation for LXR specifically, while
      upstream substitutions into AA or TA increase complex formation for LXR and, to a
      lesser extent, T3R. The preference of this in vitro complex formation was shown
      to correlate well with the functional activity of the nuclear receptors in living
      cells. The results of this study allow (i) a more detailed understanding of known
      REs, (ii) a more straightforward search for putative REs in newly identified
      promoter sequences, for example, of the whole human genome, and (iii) a more
      precise prediction of the hormone responsiveness of the respective genes.

PMID- 12210770
TI  - Styrylquinazoline derivatives as HIV-1 integrase inhibitors.
AB  - Styrylquinazoline derivatives were prepared by Perkin condensation and evaluated
      for inhibitory activity against HIV-1 integrase. Among them, compound 5c
      containing a free catechol ring was the most potent (IC(50)=0.8 +/- 1.9
      microM)and showed 6-fold more potency than the corresponding styrylquinoline
      compound (IC(50) = 130.7 +/- 8.6 microM).

PMID- 12210771
TI  - Synthesis and antimicrobial activity of some 2-[p-substituted-phenyl]benzoxazol-5
      yl-arylcarboxyamides.
AB  - New 2-[p-substituted-phenyl ]benzoxazol-5-yl-arylcarboxyamides derivatives have
      been synthesized by reacting 5-amino-2-[p-substituted-phenyl ]benzoxazoles with
      substituted-arylcarboxylic acid chlorides. The structures of the synthesized
      compounds were confirmed by IR and (1)H NMR spectral data. Antimicrobial
      activities of the compounds were investigated using the two-fold serial dilution
      technique against different Gram-positive and Gram-negative bacteria and the
      yeast C. albicans in comparison with standard drugs. Microbiological results
      indicated that the synthesized compounds possess a broad spectrum of activity,
      having an MIC value of 25-200 microg/mL at molar concentration values of 3.45 x
      10(-5) and 5.74 x 10(-4) against the tested microorganisms.

PMID- 12210772
TI  - Pyrido[2, 3-d]pyrimidines and pyrimido[5',4':5, 6]pyrido[2, 3-d]pyrimidines as
      new antiviral agents: synthesis and biological activity.
AB  - A series of 7-amino- and 7-oxo-5-aryl-6-cyanopyrido[2, 3-d]pyrimidines, 4 and 11,
      respectively, and pyrimido [5', 4':5, 6]pyrido[2, 3-d]pyrimidine derivatives 6
      and 7 was synthesized and investigated as antiviral agents. Different synthetic
      strategies for the preparation of the target compounds were explored. A synthetic
      procedure for 4 and 11 starting with 6-amino-1, 2, 3, 4-tetrahydro-2, 4
      dioxopyrimidine, proper aldehyde, and malononitrile or ethyl cyanoacetate,
      respectively, in a one-pot reaction proved to be the method of choice for
      preparation of compounds of such type. Construction of another pyrimidine ring on
      the pyridine nucleus of compound 4 was achieved either by reaction with phenyl
      iso(thio)cyanate or with formic acid to yield 6 and 7, respectively. The
      structure of the prepared compounds was confirmed through elemental analysis and
      spectral investigation. Most of the newly synthesized compounds were subjected to
      antiviral activity testing against herpes simplex virus (HSV) where some of them
      show good activities.

PMID- 12210773
TI  - Eosin Y as an internal standard for a plate reader-based quantitation of a
      histone deacetylase substrate.
AB  - Ongoing interest in histone deacetylase (HDAC) inhibitors as potential anticancer
      drugs and mechanistic tools for the study of gene regulation is driving the
      improvement of assay techniques for the determination of HDAC activity. We
      previously reported the first non-isotopic substrate for HDAC. A plate reader
      based determination of the substrate conversion utilized a boraindacene as an
      internal standard which is no longer commercially available. We report here that
      Eosin Y is a suitable replacement for that purpose, leading to a validated HDAC
      assay with increased throughput.

PMID- 12210774
TI  - Anti-HIV activity of thiosemicarbazone and semicarbazone derivatives of (+/-)-3
      menthone.
AB  - A series of thiosemicarbazones and semicarbazone derivatives of (+/-)-3-menthone
      have been synthesized and their anti-HIV activity evaluated against HIV
      1(III(B))and HIV-2 (ROD). The studies revealed that maximum protection is offered
      by chloro-substituted derivatives 2 and 7 against HIV-1 (III(B)) and HIV-2 (ROD).

PMID- 12210775
TI  - 3-Alkyl- and 3-aryl-7H-furo[3,2-g]-1-benzopyran-7-ones: synthesis,
      photoreactivity, and fluorescence properties.
AB  - A series of 3-alkyl- and 3-aryl-7H-furo[3, 2-g]-1-benzopyran-7-ones, known as
      linear furocoumarins, was synthesized and evaluated for their dark- and
      photobinding (crosslink formation) with DNA as well as for their
      spectrophotometric and fluorescent properties, lipophilicity, and ability to
      photobleach N, N-dimethyl-p-nitrosoaniline (RNO) after irradiation with UVA
      light. 8-Methoxypsoralen (8-MOP, 9-methoxy-7H-furo[3, 2-g]-1-benzopyran-7-one)
      and 4, 5', 8-trimethylpsoralen (TMP, 2, 5, 9-trimethyl-7H-furo[3, 2-g]-1
      benzopyran-7-one) were used as reference compounds in all tests. The
      investigations support the formation of a molecular complex between the
      furocoumarins and DNA. Crosslink formation with DNA after irradiation with UVA
      light was detectable for compounds with a methyl or phenyl substituent in
      position 3, but not for those bearing either a tert-butyl, a 4-methoxyphenyl, or
      a 2, 5-dimethoxyphenyl group. All furocoumarins exhibited sufficient absorption
      in the UVA wavelength range and are fluorescent. All compounds showed a higher
      lipophilicity than 8-MOP. Generally the 3-alkyl substituted furocoumarins had a
      capacity to photobleach RNOwhich was higher than that of the 3-aryl substituted
      ones. Some of the 3-aryl substituted furocoumarins displayed a photobleaching
      ability which was similar to or lower than that of 8-MOP.

PMID- 12210776
TI  - Synthesis and antibacterial activity of 1beta-methylcarbapenems having a 2, 2
      disubstituted-1, 3-diazabicyclo[3.3.0]octan-4-one moiety and related compounds.
      Part III.
AB  - The synthesis of new series of 1beta-methylcarbapenems having a 2, 2
      disubstituted-1, 3-diazabicyclo[3.3.0]octan- and -[4.3.0]nonan-4-one moiety is
      described. Their in vitro antibacterial activities against both Gram-positive and
      Gram-negative bacteria were tested and the effect of the substituent of the
      bicyclic ring was investigated. A particular compound (16 f) bearing a
      hydroxymethyl group showed the most potent antibacterial activity and the
      compound (17 a) with a 1, 3-diazabicyclo[4.3.0]nonane moiety exhibited excellent
      stability against renal dehydropeptidase-I (DHP-I) to Meropenem.

PMID- 12210777
TI  - Synthesis and benzodiazepine receptor binding activity of 2, 9-disubstituted
      quinolino[2', 3'-5, 4](3-pyrazolino)[3, 2-b]purin-4-ones.
AB  - 2, 9-Disubstituted quinolino[2', 3'-5, 4](3-pyrazolino)pyrimidin-2-ones and purin
      4-ones were synthesized and their benzodiazepine receptor activity was evaluated
      for their ability to displace [(3)H]R015-1788 from its specific binding in bovine
      brain membranes. Compound 5c caused 83 +/- 8 %inhibition in [(3)H]R015-1788
      specific benzodiazepine receptor binding followed by compounds 5f, 5h, and 5i
      while other analogs were inactive at 10 microM concentration.

PMID- 12210778
TI  - Synthesis and antitumor evaluation of new polysubstituted thiazole and derived
      thiazolo[4, 5-d]pyrimidine systems.
AB  - The synthesis of three categories of compounds containing the 1H-pyrazole ring
      linked to some dihydrothiazoles, thiazolidinones, and thiazolo[4, 5-d]pyrimidines
      through different linkages is described. Nine of the newly synthesized target
      compounds were selected by the NCI for in-vitro antitumor screening. Four
      compounds, namely 4a, 4b, 13, and 14, exhibited a broad spectrum of antitumor
      activity against most of the tested tumor cell lines. Compound 4a, 3-phenyl-4
      amino-5-(3, 5-dimethyl-1-phenyl-1H-pyrazole-4
      methylidenehydrazinocarbonyl)thiazole-2(3H)-thione proved to be the most active
      antitumor agent in the present study with GI(50), TGI, and LC(50) MG-MID values
      of 3.93, 41.7, and 91.2 microM, respectively. The same compound also exhibited
      high selectivity towards CNS SNB-75 and Ovarian IGROV1 cancer cell lines at both
      the GI(50) and TGI levels. Compound 4b, 3-(4-chlorophenyl)-4-amino-5-(3, 5
      dimethyl-1-phenyl-1H-pyrazole-4-methylidenehydra-zinocarbonyl) thiazole-2(3H)
      thione showed nearly the same pattern of activity as 4a but to a lesser extent.
      Compounds 13 and 14 displayed moderate antitumor activity against most of the
      tested tumor cell lines with GI(50) MG-MID values range of 20.4-80.6 microM and
      TGI MG-MID values of 55.5-95.5 microM.

PMID- 12210779
TI  - Synthesis and multidrug-resistance modulating activity of a series of
      thienothiazines.
AB  - A series of thienothiazines was synthesized and tested for their ability to
      inhibit P-glycoprotein, which is responsible for multidrug resistance in tumor
      cells. Highest activity was found for compounds with a homoveratryl side chain,
      which is also present in other modulators of multidrug resistance, such as
      verapamil. Although for several classes of MDR-modulators lipophilicity was shown
      to be a major determinant for high activity, no satisfactory correlation was
      obtained for the set of thienothiazines (r = 0.35). However, the use of molar
      refractivity as descriptor yields a good correlation with biological activity.
      This gives renewed evidence for the importance of molar refractivity and
      indicates that, in addition to lipophilicity, polar interactions also play an
      important role in ligand/receptor interaction.

PMID- 12210780
TI  - Synthesis and antitumor activity of enantiomerically pure [1,2-diamino-1-(4
      fluorophenyl)propane]dichloroplatinum(II) complexes.
AB  - Enantiomerically pure 1, 2-diamino-1-(4-fluorophenyl)propanes were synthesized by
      stereospecific and stereoselective procedures by use of the (1R, 2S)- and (1S,
      2R)-2-amino-1-(4-fluorophenyl)propanols (12a) as intermediates. The enantiomeric
      purity was determined by (1)H NMR spectroscopy after conversion of the
      propanolamines and the diamines with (1R)-myrtenal into mono- and diimines. For
      the coordination to platinum the diamines were reacted with K(2)PtCl(4). The
      resulting dichloroplatinum(II) complexes 4F-Ph/Me-PtCl(2) were tested for
      antiproliferative activity on the MCF-7 breast cancer cell line. (SS)- and (RR)
      4F-Ph/Me-PtCl(2) produced the strongest inhibitory effect. Both complexes showed
      cytocidal effects, (SS)-4F-Ph/Me-PtCl(2) even in a concentration of 1 microM. The
      (1S, 2R)- and (1R, 2S)-configurated complexes were far less active (SS > RR > RS
      = SR) and comparable in this respect with the standard cisplatin.

PMID- 12210781
TI  - New neurons for aging brains.

PMID- 12210782
TI  - Neuroplasticity in old age: sustained fivefold induction of hippocampal
      neurogenesis by long-term environmental enrichment.
AB  - Neurons are continually born from endogenous stem cells and added to the dentate
      gyrus throughout life, but adult hippocampal neurogenesis declines precipitously
      with age. Short-term exposure to an enriched environment leads to a striking
      increase in new neurons, along with a substantial improvement in behavioral
      performance. Could this plastic response be relevant for explaining the
      beneficial effects of leading "an active life" on brain function and pathology?
      Adult hippocampal neurogenesis in mice living in an enriched environment from the
      age of 10 to 20 months was fivefold higher than in controls. Relatively, the
      increase in neuronal phenotypes was entirely at the expense of newly generated
      astrocytes. This cellular plasticity occurred in the context of significant
      improvements of learning parameters, exploratory behavior, and locomotor
      activity. Enriched living mice also had a reduced lipofuscin load in the dentate
      gyrus, indicating decreased nonspecific age-dependent degeneration. Therefore, in
      mice signs of neuronal aging can be diminished by a sustained active and
      challenging life, even if this stimulation started only at medium age. Activity
      exerts not only an acute but also a sustained effect on brain plasticity.

PMID- 12210783
TI  - Pallidal stimulation for parkinsonism: improved brain activation during sequence
      learning.
AB  - We used (15)O-labeled water and positron emission tomography to assess the effect
      of deep brain stimulation of the internal globus pallidus on motor sequence
      learning in Parkinson's disease. Seven right-handed patients were scanned on and
      off stimulation while they were performing a motor sequence learning task and a
      kinematically matched motor execution reference task. The scans were performed
      after a 12-hour medication washout. Stimulation parameters were adjusted for
      maximal motor improvement; experimental task parameters were held constant across
      stimulation conditions. Internal globus pallidus stimulation improved motor
      ratings by 37% (p < 0.01). During the sequence learning task, stimulation
      improved performance as measured by several correct anticipatory movements (p <
      0.01) and by verbal report (p < 0.001). Concurrent positron emission tomography
      imaging during learning demonstrated significant (p < 0.01) increases in brain
      activation with stimulation in the left dorsolateral prefrontal cortex,
      bilaterally in premotor cortex, and in posterior parietal and occipital
      association areas. Stimulation did not affect the activity of these regions
      during the performance of the motor execution reference task. These findings
      suggest that internal globus pallidus deep brain stimulation can enhance the
      activity of prefrontal cortico-striato-pallidothalamic loops and related
      transcortical pathways. Improved sequence learning with stimulation may be
      directly related to these functional changes.

PMID- 12210784
TI  - A nonischemic forearm exercise test for McArdle disease.
AB  - Ischemic forearm exercise invariably causes muscle cramps and pain in patients
      with glycolytic defects. We investigated an alternative diagnostic exercise test
      that may be better tolerated. Nine patients with McArdle disease, one with the
      partial glycolytic defect phosphoglycerate mutase deficiency, and nine matched,
      healthy subjects performed the classic ischemic forearm protocol and an identical
      protocol without ischemia. Blood was sampled in the median cubital vein of the
      exercised arm. Plasma lactate level increased similarly in healthy subjects
      during ischemic (Delta5.1 +/- 0.7mmol L(-1)) and non-ischemic (Delta4.4 +/- 0.3)
      tests and decreased similarly in McArdle patients (Delta-0.10 +/- 0.02 vs Delta
      0.40 +/- 0.10mmol L(-1)). Postexercise peak lactate to ammonia ratios clearly
      separated patients and healthy controls in ischemic (McArdle, 4 +/- 2 [range, 1
      12]; partial glycolytic defect phosphoglycerate mutase deficiency, 6; healthy, 33
      +/- 4 [range, 17-56]) and non-ischemic (McArdle, 5 +/- 1 [range, 1-10]; partial
      glycolytic defect phosphoglycerate mutase deficiency, 5; healthy, 42 +/- 3
      [range, 35-56]) protocols. Similar differences in lactate to ammonia ratio
      between patients and healthy subjects were observed in two other work protocols
      using intermittent handgrip contraction at 50% and static handgrip exercise at
      30% of maximal voluntary contraction force. All patients developed pain and
      cramps during the ischemic test, and four had to abort the test prematurely. No
      patient experienced cramps in the non-ischemic test, and all completed the test.
      The findings indicate that the diagnostic ischemic forearm test for glycolytic
      disorders should be replaced by an aerobic forearm test.

PMID- 12210785
TI  - Gene transfer of HSP72 protects cornu ammonis 1 region of the hippocampus neurons
      from global ischemia: influence of Bcl-2.
AB  - We investigated whether HSV gene transfer of HSP72 in vivo and in vitro: (1)
      protected cornu ammonis 1 region of the hippocampus neurons from global cerebral
      ischemia; and (2) affected Bcl-2 expression. HSV vectors expressing HSP72 and
      beta-galactosidase (reporter) or beta-galactosidase only (control vector) were
      injected into cornu ammonis 1 region of the hippocampus 15 hours before induction
      of global cerebral ischemia (n = 10) and sham-operated rats (n = 8). HSP72 vector
      treated rats displayed significantly more surviving transfected neurons (X-gal
      positive, 31 +/- 8) compared with control vector-treated rats (10 +/- 4) after
      global cerebral ischemia. Sham-operated rats displayed similar numbers of X-gal
      positive neurons (HSP72 vector 18 +/- 8 vs control vector 20 +/- 7). The
      percentage of beta-galactosidase and Bcl-2 coexpressing neurons in HSP72-treated
      rats after global cerebral ischemia (84 +/- 4%) was greater than that in control
      vector-treated rats (58 +/- 9%). The percentage of beta-galactosidase and Bcl-2
      coexpressing neurons in sham-operated rats was similar in HSP72 (93 +/- 7%) and
      in control vector-treated rats (88 +/- 12%). HSP72 vector transfection led to 12
      times as much Bcl-2 expression as the control vector in uninjured hippocampal
      neuronal cultures. In injured (oxygen-glucose deprivation) hippocampal neuron
      cultures, HSP72 vector transfection led to 2.8 times as much Bcl-2 expression as
      control vector. We show that HSP72 overexpression protects cornu ammonis 1 region
      of the hippocampus neurons from global cerebral ischemia, and that this
      protection may be mediated in part by increased Bcl-2 expression.

PMID- 12210786
TI  - Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia Aging
      Study.
AB  - Inflammatory responses are associated with cardiovascular disease and may be
      associated with dementing disease. We evaluated the long-term prospective
      association between dementia and high-sensitivity C-reactive protein, a
      nonspecific marker of inflammation. Data are from the cohort of Japanese American
      men who were seen in the second examination of the Honolulu Heart Program (1968
      1970) and subsequently were reexamined 25 years later for dementia in the
      Honolulu-Asia Aging Study (1991-1996). In a random subsample of 1,050 Honolulu
      Asia Aging Study cases and noncases, high-sensitivity C-reactive protein
      concentrations were measured from serum taken at the second examination; dementia
      was assessed in a clinical examination that included neuroimaging and
      neuropsychological testing and was evaluated using international criteria.
      Compared with men in the lowest quartile (<0.34mg/L) of high-sensitivity C
      reactive protein, men in the upper three quartiles had a 3-fold significantly
      increased risk for all dementias combined, Alzheimer's disease, and vascular
      dementia. For vascular dementia, the risk increased with increasing quartile.
      These relations were independent of cardiovascular risk factors and disease.
      These data support the view that inflammatory markers may reflect not only
      peripheral disease, but also cerebral disease mechanisms related to dementia, and
      that these processes are measurable long before clinical symptoms appear.

PMID- 12210787
TI  - Peripheral F2-isoprostanes and F4-neuroprostanes are not increased in Alzheimer's
      disease.
AB  - Quantitative biomarkers of oxidative damage, such as the F(2)-isoprostanes
      (IsoPs) and F(4)-neuroprostanes (F(4)-NeuroPs), may be useful in assessing
      progression and response to therapeutics in patients with Alzheimer's disease.
      F(2)-IsoPs and F(4)-NeuroPs are reproducibly increased in brain and cerebrospinal
      fluid of Alzheimer's disease patients; however, results in blood and urine have
      been conflicting. We tested the hypothesis that F(2)-IsoPs and F(4)-NeuroPs in
      plasma or urine quantitatively reflect oxidative damage to the central nervous
      system. Our results showed that urine levels of F(2)-IsoPs or their major
      metabolite were not significantly different between 56 Alzheimer's disease
      patients and 34 controls. In addition, urine and cerebrospinal fluid F(2)-IsoP
      levels in 32 Alzheimer's disease patients did not correlate. Supporting these
      conclusions, elevated rat cerebral F(2)-IsoPs and F(4)-NeuroPs after systemic
      exposure to kainic acid were not associated with a significant change in their
      plasma or urine levels. These results show that plasma and urine F(2)-IsoPs and
      F(4)-NeuroPs do not accurately reflect central nervous system levels of these
      biomarkers and are not reproducibly elevated in body fluids outside of central
      nervous system in Alzheimer's disease patients. These results should guide the
      organization of clinical trials now being planned for patients with Alzheimer's
      disease.

PMID- 12210788
TI  - Differences in membrane properties of axonal and demyelinating Guillain-Barre
      syndromes.
AB  - Guillain-Barre syndrome is classified into acute motor axonal neuropathy (AMAN)
      and acute inflammatory demyelinating polyneuropathy (AIDP) by electrodiagnostic
      and pathological criteria. In AMAN, the immune attack appears directed against
      the axolemma and nodes of Ranvier. Threshold tracking was used to measure indices
      of axonal excitability (refractoriness, supernormality, and threshold
      electrotonus) for median nerve axons at the wrist of patients with AMAN (n = 10)
      and AIDP (n = 8). Refractoriness (the increase in threshold current during the
      relative refractory period) was greatly increased in AMAN patients, but the
      abruptness of the threshold increases at short interstimulus intervals indicated
      conduction failure distal to the stimulation (ie, an increased refractory period
      of transmission). During the 4 week period from onset, the high refractoriness
      returned toward normal, and the amplitude of the compound muscle action potential
      increased, consistent with improvement in the safety margin for impulse
      transmission in the distal nerve. In contrast, refractoriness was normal in AIDP,
      even though there was marked prolongation of distal latencies. Supernormality and
      threshold electrotonus were normal in both groups of patients, suggesting that,
      at the wrist, membrane potential was normal and pathology was relatively minor.
      These results support the view that the predominantly distal targets of immune
      attack are different for AMAN and AIDP. Possible mechanisms for the reduced
      safety factor in AMAN are discussed.

PMID- 12210789
TI  - Premotor cortex is involved in restoration of gait in stroke.
AB  - Cortical activation during hemiplegic gait was assessed in six nonambulatory
      patients with severe stroke (four men, two women; four with right and two with
      left hemiplegia; 57 years old and 3 months after stroke on average), using a near
      infrared spectroscopic imaging system. Each patient performed tasks of treadmill
      walking (0.2km/hr), alternated with rest every 30 seconds for four repetitions,
      under partial body weight support, either with mechanical assistance in swinging
      the paretic leg control (CON) or with a facilitation technique that enhanced
      swinging of the paretic leg (FT), provided by physical therapists. Gait
      performance was associated with increased oxygenated hemoglobin levels in the
      medial primary sensorimotor cortex in the unaffected hemisphere greater than in
      the affected hemisphere. Both cortical mappings and quantitative data showed that
      the premotor activation in the affected hemisphere was enhanced during hemiplegic
      gait. There was also a prominent activation in the presupplementary motor area.
      Overall cortical activations and gait performance were greater in walking with FT
      than with CON. These indicate that multiple motor areas including the premotor
      cortex and presupplementary motor area might play important roles in restoration
      of gait in patients with severe stroke.

PMID- 12210790
TI  - Cofactors of mitochondrial enzymes attenuate copper-induced death in vitro and in
      vivo.
AB  - Copper toxicity contributes to neuronal death in Wilson's disease and has been
      speculatively linked to the pathogenesis of Alzheimer's and prion diseases. We
      examined copper-induced neuronal death with the goal of developing
      neuroprotective strategies. Copper catalyzed an increase in hydroxyl radical
      generation in solution, and the addition of 20 microM copper for 22 hours to
      murine neocortical cell cultures induced a decrease in ATP levels and neuronal
      death without glial death. This selective neuronal death was associated with
      activation of caspase-3 and was reduced by free radical scavengers and Z-Val-Ala
      Asp fluoromethylketone, consistent with free radical-mediated injury leading to
      apoptosis. Pyruvate dehydrogenase is especially vulnerable to inhibition by
      oxygen free radicals, and the upstream metabolites, pyruvate,
      phosphoenolpyruvate, and 2-phosphoglycerate were elevated in cortical cells after
      toxic exposure to copper. One approach to protecting pyruvate dehydrogenase from
      oxidative attack might be to enhance binding to cofactors. Addition of thiamine,
      dihydrolipoic acid, or pyruvate reduced copper-induced neuronal death. To test
      efficacy in vivo, we added 1% thiamine to the drinking water of Long Evans
      Cinnamon rats, an animal model of Wilson's disease. This thiamine therapy
      markedly extended life span from 6.0 +/- 1.6 months to greater than 16 months.

PMID- 12210791
TI  - Novel antibodies to synuclein show abundant striatal pathology in Lewy body
      diseases.
AB  - Intracytoplasmic inclusions composed of alpha-synuclein (alpha-syn) are
      characteristic of neurodegenerative Lewy body disorders. Using novel monoclonal
      antibodies raised against altered alpha-syn, we uncovered an unprecedented and
      extensive burden of alpha-syn pathology in the striatum of Lewy body disorders.
      The highest density of striatal pathology was observed in patients with a
      combination of Alzheimer's disease and dementia with Lewy bodies or pure dementia
      with Lewy bodies, and these alpha-syn aggregates may contribute to the
      parkinsonism seen in these disorders.

PMID- 12210792
TI  - Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of
      autosomal dominant or recessive progressive external ophthalmoplegia.
AB  - One form of familial progressive external ophthalmoplegia with multiple
      mitochondrial DNA deletions recently has been associated with mutations in POLG1,
      the gene encoding pol gammaA, the catalytic subunit of mitochondrial DNA
      polymerase. We screened the POLG1 gene in several PEO families and identified
      five different heterozygous missense mutations of POLG1 in 10 autosomal dominant
      families. Recessive mutations were found in three families. Our data show that
      mutations of POLG1 are the most frequent cause of familial progressive external
      ophthalmoplegia associated with accumulation of multiple mitochondrial DNA
      deletions, accounting for approximately 45% of our family cohort.

PMID- 12210793
TI  - Progressive loss of cardiac sympathetic innervation in Parkinson's disease.
AB  - This study addressed whether cardiac sympathetic denervation progresses over time
      in Parkinson's disease. In 9 patients without orthostatic hypotension, 6
      [(18)F]fluorodopamine positron emission tomography scanning was repeated after a
      mean of 2 years from the first scan. 6-[(18)F]fluorodopamine-derived
      radioactivity was less in the second scan than in the first scan, by 31% in the
      left ventricular free wall and 16% in the septum. In Parkinson's disease, loss of
      cardiac sympathetic denervation progresses in a pattern of loss suggesting a
      dying-back mechanism.

PMID- 12210794
TI  - No mutation in the TRKA (NTRK1) gene encoding a receptor tyrosine kinase for
      nerve growth factor in a patient with hereditary sensory and autonomic neuropathy
      type V.
AB  - Hereditary sensory and autonomic neuropathy type IV (HSAN-IV) and type V (HSAN-V)
      are autosomal recessive genetic disorders, both characterized by a lack of pain
      sensation. We report a girl with clinical and neurophysiological findings
      consistent with a diagnosis of HSAN-V. We sequenced her TRKA gene, encoding a
      receptor tyrosine kinase for nerve growth factor and responsible for HSAN-IV, but
      we could not detect any mutation. These data indicate that a gene (or genes)
      other than TRKA is probably responsible for HSAN-V in some patients.

PMID- 12210795
TI  - X-linked creatine deficiency syndrome: a novel mutation in creatine transporter
      gene SLC6A8.
AB  - Among creatine deficiency syndromes, an X-linked condition related to a defective
      creatine transport into the central nervous system has been described recently.
      Hallmarks of the disease are the absence of a creatine signal at brain
      spectroscopy, increased creatine levels in blood and urine, ineffectiveness of
      oral supplementation, and a mutation in the SLC6A8 (Online Mendelian Inheritance
      in Man [OMIM] 300036) creatine transporter gene. We report on a patient in whom a
      novel mutation (1221-1223delTTC) was identified.

PMID- 12210796
TI  - Vertebrobasilar stroke as a late complication of a Blalock-Taussig shunt.
AB  - We describe a 39-year-old patient with a cerebellar infarct and a history of a
      tetralogy of Fallot corrected during childhood. This is the first documented case
      of vertebrobasilar stroke occurring as a late complication of a Blalock-Taussig
      shunt followed by total cardiac repair.

PMID- 12210797
TI  - Cerebral X-linked adrenoleukodystrophy in a girl with Xq27-Ter deletion.
AB  - An 8.5-year-old girl with a pathogenic mutation (515insC) of the ATP-binding
      cassette, subfamily D, member 1 gene (ABCD1) on her maternally derived X
      chromosome showed clinical, biochemical, and magnetic resonance imaging
      abnormalities similar to those in affected males. Cytogenetic studies led to the
      surprise finding of a de novo deletion of Xq27 on the paternally derived X
      chromosome. A bone marrow transplant had an apparently favorable effect.
      Cytogenetic studies should be performed in all severely symptomatic X-linked
      adrenoleukodystrophy heterozygotes.

PMID- 12210798
TI  - A novel mutation in the deoxyguanosine kinase gene causing depletion of
      mitochondrial DNA.
AB  - Recently, a homozygous single-nucleotide deletion in exon 2 of the deoxyguanosine
      kinase gene (DGUOK) was identified as the disease-causing mutation in 3
      apparently unrelated Israeli-Druze families with depleted hepatocerebral
      mitochondrial DNA. We have discovered a novel homozygous nonsense mutation in
      exon 3 of DGUOK (313C-->T) from a patient born to nonconsanguineous German
      parents. This finding shows that mutations in DGUOK causing mitochondrial DNA
      depletion are not confined to a single ethnic group.

PMID- 12210799
TI  - Dyskinesias and grip control in Parkinson's disease are normalized by chronic
      stimulation of the subthalamic nucleus.
AB  - Deep-brain stimulation of the subthalamic nucleus appears to reduce levodopa
      induced dyskinesias, but whether this effect is caused by the reduction of the
      total levodopa ingestion or represents a direct effect on the motor system is
      unknown. Precision grip force of grasping movements and levodopa-induced
      dyskinesias was analyzed in 10 parkinsonian patients before and after 3 months of
      deep-brain stimulation of the subthalamic nucleus. Peak grip force was abnormally
      increased before surgery in the off-drug state and, particularly, in the on-drug
      state (sensitization). This grip force upregulation normalized with chronic deep
      brain stimulation in both conditions (desensitization). Peak-dose dyskinesias
      also improved, and off-dystonia was completely abolished. Mean dosage of
      dopaminergic drugs was reduced, but force overflow and dyskinesias were equally
      improved in 2 patients without a reduction. Despite the same single levodopa test
      dose, force excess and levodopa-induced dyskinesias were drastically reduced
      after 3 months of deep-brain stimulation of the subthalamic nucleus. This
      indicates that direct effects of deep-brain stimulation of the subthalamic
      nucleus on levodopa-induced dyskinesias are likely to occur. Grip force overflow
      is a promising parameter to study the desensitizing effect of chronic deep-brain
      stimulation on levodopa-induced dyskinesias.

PMID- 12210800
TI  - Demonstration of acute ischemic lesions in the fetal brain by diffusion magnetic
      resonance imaging.
AB  - The possibility of detecting acute hypoxic-ischemic brain lesions by prenatal
      magnetic resonance imaging or ultrasound is low. We present a case of a fetus
      with a vein of Galen arteriovenous malformation in whom prenatal diffusion
      weighted magnetic resonance imaging at 33 weeks of gestation clearly detected
      cerebral acute ischemic lesions, associated with remarkable decrease of the
      average apparent diffusion coefficient, whereas T2-weighted imaging was still not
      informative.

PMID- 12210801
TI  - Selective loss of cholinergic sudomotor fibers causes anhidrosis in Ross
      syndrome.
AB  - Ross syndrome consists of segmental hyperhidrosis with widespread anhidrosis,
      Adie syndrome, and areflexia. The cause of this disorder is unknown. Selective
      degeneration of cholinergic fibers or of neural crest-derived structures has been
      suggested. We present clinical and skin biopsy data of 4 patients, providing
      evidence of reduced cholinergic sweat gland innervation in hypohidrotic skin by
      morphometric analysis. These findings indicate a selective degenerative process
      of the cholinergic sudomotor neurons.

PMID- 12210802
TI  - Normokalemic periodic paralysis revisited: does it exist?
AB  - Normokalemic periodic paralysis (normoKPP) is well established in the literature,
      but there are doubts as to whether it exists as a discrete entity. Retrospective
      clinical and molecular analysis has confirmed suspicions that most normoKPP
      families actually have a variant of hyperkalemic periodic paralysis (hyperKPP)
      due to a mutation of the muscle-specific sodium channel gene (SCN4A). However,
      the original normoKPP family described by Poskanzer and Kerr (Poskanzer DC, Kerr
      DNS. A third type of periodic paralysis, with normokalemia and favourable
      response to sodium chloride. Am J Med 1961;31:328-342) has remained unchallenged.
      We identified the Met1592Val mutation of SCN4A in an affected descendent of this
      original normoKPP family. This is the final piece in the puzzle: normoKPP is
      actually a variant of hyperKPP and is not a distinct disorder.

PMID- 12210803
TI  - Human antibodies against amyloid beta peptide: a potential treatment for
      Alzheimer's disease.
AB  - Naturally occurring antibodies directed against beta-amyloid (Abeta) were
      detected in intravenous immunoglobulin preparations. After intravenous
      immunoglobulin treatment in patients with different neurological diseases, total
      Abeta and Abeta(1-42) in the cerebrospinal fluid was reduced significantly
      compared with baseline values. In the serum, total Abeta levels increased after
      intravenous immunoglobulin treatment, whereas no significant change was observed
      in Abeta(1-42) levels. Antibodies against Abeta were found to be increased in the
      serum and cerebrospinal fluid after intravenous immunoglobulin treatment. This
      study provides evidence that intravenous immunoglobulin or purified Abeta
      antibodies may modify Abeta and Abeta(1-42) levels, suggesting potential utility
      as a therapy for Alzheimer disease.

PMID- 12210808
TI  - Bcl-2 family of proteins in indolent B-cell non-Hodgkin's lymphoma: study of 116
      cases.
AB  - The bcl-2 family of proteins comprises both antagonists and agonists of
      apoptosis. We have investigated whether subsets of indolent B-cell non-Hodgkin's
      lymphoma (IB-NHL) differ in the expression of the bcl-2 family members; 116 cases
      of IB-NHL, composed of chronic lymphocytic leukemia (CLL, n = 48), follicular
      lymphoma (FL, n = 38), marginal zone B-cell lymphoma (MZBCL, n = 15), and mantle
      cell lymphoma (MCL, n = 15), were investigated for expression of bcl-2, bcl-X,
      mcl-1, bax, and bak proteins by immunohistochemistry. Expression of bcl-2 and bcl
      X proteins was moderate/high among most IB-NHLs. Expression of mcl-1 was
      low/absent in most cases of CLL and MCL and low/moderate in most cases of FL and
      MZBCL. Most MCLs did not express bax protein. Bax expression was absent/low among
      most cases of CLL and low/moderate among most cases of FL and MZBCL. Expression
      of bak was moderate/low among most cases of CLL, MZBCL, and MCL but was
      absent/low among most cases of FL. The different subsets of IB-NHLs differ in
      their expression of mcl-1, bax, and bak proteins.

PMID- 12210804
TI  - Role of SCA2 mutations in early- and late-onset dopa-responsive parkinsonism.

PMID- 12210807
TI  - Spectrum of beta-thalassemia mutations and their association with allelic
      sequence polymorphisms at the beta-globin gene cluster in an Eastern Indian
      population.
AB  - In this report, the spectrum of beta-thalassemia mutations and genotype-to
      phenotype correlations were defined in large number of patients (beta-thalassemia
      carriers and major) with varying disease severity in an Eastern Indian population
      mainly from the state of West Bengal. The five most common beta-thalassemia
      mutations were detected, which included IVS1-5 (G-->C), codon 15 (G-->A), codon
      26 (G-->A), codon 30 (G-->C), and codon 41/42 (-TCTT). These accounted for 85% in
      80 beta-thalassemic alleles deciphered from 56 patients, including beta
      thalassemia major and carriers, and 15% of alleles remained uncharacterized in
      these patients. Expression of the human beta-globin gene is regulated by an array
      of cis-acting DNA elements, including five DNase I hypersensitive sites (HSs) in
      the locus control region (LCR), promoters that incorporate certain silencer
      elements, and enhancers at 3' of the beta-globin gene. For detailed studies and
      to understand the molecular basis of beta-thalassemia, we studied two groups of
      subjects: a group of 12 patients from four families having beta-thalassemia major
      and carrier phenotype and a control group of 26 healthy individuals. In these two
      groups, we examined portions of the beta-globin gene locus control region HSs 1,
      2, 3, and 4, which included the (CA)(x)(TA)(y) repeat motif, the
      (AT)(x)N(y)(AT)(z) repeat motif, the inverted repeat sequence TGGGGACCCCA, the
      promoter region of the (G)gamma-globin gene, an (AT)(x)(T)(y) repeat 5' of the
      silencer region, and the beta-globin gene and its 3' flanking region. We
      investigated the allelic sequence polymorphisms in these regions and their
      association with the beta-thalassemia mutations to know the possible genotype
      phenotype relationship in beta-thalassemia patients. An analysis of cis-acting
      regulatory regions showed varied sequence haplotypes associated with some
      frequent beta-thalassemia mutations in this Eastern Indian population.

PMID- 12210809
TI  - Follow-up examinations including sequential bone marrow biopsies in essential
      thrombocythemia (ET): a retrospective clinicopathological study of 120 patients.
AB  - Diagnosis of essential thrombocythemia (ET) has been usually established by
      regarding the criteria of the Polycythemia Vera Study Group. Accordingly, a
      retrospective clinicopathological study was performed on 120 patients with a
      follow-up ranging between 5 and 13 years and repeated bone marrow trephine
      examinations. Following the new WHO classification, at presentation patients
      revealed three distinctive patterns of bone marrow (BM) features: (true) ET in 43
      patients, prefibrotic idiopathic myelofibrosis (IMF) in 50 patients, and early
      IMF in 27 patients. Heterogeneity of morphological features was associated with
      correspondingly expressed laboratory data. Contrasting initial and early IMF,
      patients with true ET displayed an about 80% probability to lack splenomegaly,
      anemia, and increase in the LDH and LAP values and also failed to show any
      myeloblasts or erythroblasts on the peripheral blood films. Follow-up
      examinations including sequential BM biopsies (mean interval 39 +/- 31 months)
      disclosed that of the 43 patients with true ET only one developed an increase in
      reticulin. On the other hand, 65 of 77 patients with prefibrotic and early IMF
      evolved into overt myelofibrosis-osteosclerosis. Moreover, survival analysis
      demonstrated significant differences in our patients. A neglectable proportion of
      life loss according to a sex- and age-matched general population was found in
      true ET (less than 11%) opposed to IMF without or mild fibrosis (range 21% to
      32%).

PMID- 12210810
TI  - Arsenic trioxide in the treatment of newly diagnosed acute promyelocytic
      leukemia: a single center experience.
AB  - Arsenic trioxide (As(2)O(3)) has been found effective in the treatment in the
      treatment of acute promyelocytic leukemia (APML). Most studies with As(2)O(3)
      involve patients with APML who have relapsed following standard therapy. Between
      January 1998 and July 2000, 14 patients were recruited for an ongoing trial of
      As(2)O(3) in the treatment of newly diagnosed APML. Arsenic trioxide was
      administered at a dose of 10 mg/day until complete remission (CR) was achieved.
      Afterward, a consolidation course and a maintenance schedule consisting of
      As(2)O(3) as a single agent were administered over 6 months. There were 3 early
      deaths related to intra-cerebral hemorrhage: two on day 3 and one on day 4. Of
      the 11 evaluable patients, one died on day 21 secondary to uncontrolled sepsis,
      while the remaining 10 (91%) have attained CR. The average time to CR was 52.3
      days (range: 34-70 days). One patient developed an isolated central nervous
      system (CNS) relapse and subsequently went into a second CR following therapy
      with triple intrathecal chemotherapy, cranial irradiation, and an additional 4
      week course of systemic As(2)O(3). This patient, as well as the remaining nine,
      has continued to remain in CR at a median follow up of 15 months (range: 2-33
      months). Eight out of 10 patients achieved molecular remission at variable
      periods during their consolidation and maintenance schedules. One patient
      developed an ATRA syndrome and was administered daunorubicin (40 mg/day) for 2
      days. The side effects with this therapy were minimal and did not require
      cessation of therapy in any patient. There was no significant hepatic toxicity.
      In our experience, arsenic trioxide is effective in inducing and maintaining
      remission in patients with APML with minimal side effects. The optimal regimen
      and total dose required need to be defined.

PMID- 12210811
TI  - Bone marrow necrosis: clinicopathologic analysis of 20 cases and review of the
      literature.
AB  - Bone marrow necrosis (BMN) is a relatively uncommon clinicopathologic entity. The
      etiology is diverse, and malignancy, especially hematopoietic in origin, is the
      most common underlying disease of BMN. In this retrospective analysis, cases with
      BMN were re-evaluated for etiology, histopathologic details, and clinical
      manifestations. In the last 8 years, 23 cases of BMN were detected among the
      1,083 bone marrow (BM) biopsies, and the prevalence was found to be 2.2%. Three
      of these 23 cases with BMN were children, and 20 cases were in adults. Sixteen of
      these cases (80%) had underlying malignant disease, and four (20%) had
      nonmalignant disease. Among the malignant cases, three cases had acute
      myeloblastic leukemia (AML), four had relapsed Hodgkin's disease (R-HD), one had
      acute lymphoblastic leukemia (ALL), two had chronic myelocytic leukemia (CML),
      two had non-Hodgkin's lymphoma (NHL), three had disseminated intravascular
      coagulation (DIC) associated with metastatic solid tumor, and one had
      myelodysplastic syndrome/myeloproliferative syndrome (MDS/MPS). Among the
      nonmalignant cases, two had tuberculosis infection, one had anti-phospholipid
      syndrome (APS), and one had a history of drug ingestion. The most common symptoms
      were bone pain, fever, fatigue, and jaundice. The most common laboratory findings
      were variable and associated with underlying disease, but anemia, leukopenia,
      thrombocytopenia, and high LDH and alkaline phosphatase levels were detected in
      the majority of the cases, as was also seen in other series. BMN was graded
      according to the extent of necrosis in the BM biopsy, and necrosis was extensive
      in 12 cases, moderate in five cases, and mild in three cases. Increased reticulin
      was found in 16 cases; four cases had severe, eight had moderate, and four had
      mild fibrosis, and this was found to be an interesting accompanying finding in
      BMN. In conclusion malignancy is the most common cause of BMN but some
      nonmalignant conditions such as tuberculosis and APS may be the underlying cause
      of BMN.

PMID- 12210812
TI  - Cardiac abnormalities in children with sickle cell anemia.
AB  - Sickle cell anemia (SCA) results in chronic volume overload of the heart due to
      hemodilution. Previous echocardiographic studies of cardiac function in children
      with SCA have not accounted for these abnormal loading conditions. The objectives
      of this study were to (1) determine how the degree of anemia and transfusion
      status relate to cardiac findings and (2) evaluate cardiac function using load
      independent parameters of function. We evaluated 77 patients with SCA, ages 2 to
      22 years (mean +/- SD = 11.7 +/- 4.7), using physical examination,
      electrocardiography, and echocardiography. We compared two groups of patients.
      Group 1 consisted of 57 non-transfused patients, and Group 2 consisted of 20
      patients on a chronic transfusion protocol. Group 1 patients exhibited a
      significantly lower hemoglobin, higher cardiac output, and larger left
      ventricular (LV) end-diastolic dimension and LV mass than groups 2 (P < 0.05).
      However, the velocity of circumferential fiber shortening-wall stress index (a
      load-independent measure of systolic function) was normal and not statistically
      different between the two groups. Conversely, the LV myocardial performance index
      (a measure of combined systolic and diastolic function) was significantly higher
      in Group 2 (P < 0.001), possibly indicating impaired myocardial diastolic
      function. SCA in children results in a volume-overloaded heart with a significant
      increase in LV dimensions and mass, both proportional to the degree of anemia.
      Despite these abnormal loading conditions, systolic function is preserved.
      Patients on a chronic transfusion protocol may develop diastolic dysfunction
      despite iron chelation therapy.

PMID- 12210813
TI  - Spontaneous reports of thrombocytopenia in association with quinine: clinical
      attributes and timing related to regulatory action.
AB  - Quinine has been marketed in the United States (U.S.) both over-the-counter (OTC)
      and by prescription for numerous purposes, including malaria and muscle spasms.
      In 1994 and 1995, the U.S. Food and Drug Administration (FDA) acted to limit the
      marketing of quinine based on the conclusion that no data supported its safe and
      efficacious use in these settings. This report includes clinical attributes from
      the largest case series to date of apparently isolated thrombocytopenia in
      association with quinine and trends in the receipt of spontaneous adverse event
      reports to FDA's Center for Drug Evaluation and Research (CDER) for this drug
      event combination in relation to regulatory action. In this study, we reviewed
      reports of spontaneous adverse drug events received by CDER. From 1974 through
      December 2000, CDER received 397 adverse event reports for quinine. Based on
      crude, unreviewed counts, 141 (35.5%) of these reports described apparently
      isolated thrombocytopenia. Reporting for this event peaked in 1995, coincident
      with regulatory action, and has subsequently declined. After elimination of cases
      confounded by acute or chronic disease or concomitant drug therapy, 64 reports of
      quinine-associated thrombocytopenia were used to form a case series. This case
      series, including 11 cases since January 1996, supports the potential for rapid
      time-to-onset (median 7 days) and clinical severity (hospitalization reported in
      55 of the 64 cases). Although the number of reports since regulatory action is
      limited, CDER continues to receive reports of thrombocytopenia in association
      with quinine in use for nocturnal leg cramps. Extrapolation of spontaneous
      adverse event reports for a product with substantial OTC use precludes estimates
      of rates/incidence. Therefore, the effect of regulatory actions in 1994/1995 is
      difficult to measure using this approach. Although reports have decreased since
      regulatory actions on quinine, quinine remains available in the U.S. by
      prescription and in food products/dietary supplements. This case series confirms
      previous smaller series that suggest quinine-associated thrombocytopenia may
      present rapidly with symptoms of profound thrombocytopenia. Clinicians evaluating
      patients with new-onset and apparently idiopathic thrombocytopenia should
      maintain clinical vigilance for ingestion of quinine and elicit a detailed
      food/dietary supplement history from the patient.

PMID- 12210814
TI  - HIV and refractory anemia with excess blasts (RAEB).
AB  - We report the case of a 36 year old man who was hospitalized with pneumonia and
      pancytopenia with refractory anemia with excess blasts confirmed by bone marrow
      biopsy. He was subsequently found to have advanced HIV infection. Both the HIV
      infection and the myelodysplastic syndrome responded to highly active anti
      retroviral therapy (HAART) with sustained normalization of his hematologic
      abnormalities within 79 days.

PMID- 12210815
TI  - Acute rhabdomyolysis as a complication of cytarabine chemotherapy for acute
      myeloid leukemia: case report and review of literature.
AB  - Rhabdomyolysis is an unusual complication of chemotherapy that can lead to
      substantial morbidity through such complications as renal failure, infections,
      and disseminated intravascular coagulation. The syndrome has been described after
      treatment with cyclophosphamide, 5-azacytidine, interleukin-2, and interferon and
      after bone marrow transplantation. We report a patient with acute myeloid
      leukemia who developed fulminant rhabdomyolysis after treatment with a cytarabine
      containing regimen. The syndrome was complicated by acute renal failure requiring
      hemodyalisis, respiratory insufficiency, and pancreatitis. We suggest that the
      muscle damage might be related to the known ability of cytarabine to trigger the
      release of cytochrome c from the mitochondria, which could lead to uncoupling of
      the oxidative phosphorylation with subsequent depletion of ATP reserves at the
      skeletal muscle and rhabdomyolysis.

PMID- 12210816
TI  - Effective treatment with recombinant factor VIIa of severe bleeding due to
      acquired factor VIII inhibitor and acquired thrombocytopathy.

PMID- 12210817
TI  - Treatment of two patients with acquired factor VIII inhibitors using
      cyclophosphamide and prednisone.

PMID- 12210818
TI  - Origin of Hb S Antilles.

PMID- 12210819
TI  - Successful treatment with 2-chlorodeoxyadenosine of secondary lesions of the
      central nervous system in low-grade lymphoid malignancies.

PMID- 12210820
TI  - Recombinant FVIIa in the treatment of bleeding in acquired hemophilia.

PMID- 12210821
TI  - CD5-negative chronic lymphocytic leukemia or monoclonal B-lymphocytosis of
      undetermined significance?

PMID- 12210822
TI  - Paradigm shifts in Alzheimer's disease and other neurodegenerative disorders: the
      emerging role of oligomeric assemblies.
AB  - Alzheimer's disease (AD) is a progressive, neurodegenerative disorder
      characterized by amyloid deposition in the cerebral neuropil and vasculature.
      These amyloid deposits comprise predominantly fragments and full-length (40 or 42
      residue) forms of the amyloid beta-protein (Abeta) organized into fibrillar
      assemblies. Compelling evidence indicates that factors that increase overall
      Abeta production or the ratio of longer to shorter forms, or which facilitate
      deposition or inhibit elimination of amyloid deposits, cause AD or are risk
      factors for the disease. In vitro studies have demonstrated that fibrillar Abeta
      has potent neurotoxic effects on cultured neurons. In vivo experiments in non
      human primates have demonstrated that Abeta fibrils directly cause pathologic
      changes, including tau hyperphosphorylation. In concert with histologic studies
      revealing a lack of tissue injury in areas of the neuropil in which non-fibrillar
      deposits were found, these data suggested that fibril assembly was a prerequisite
      for Abeta-mediated neurotoxicity in vivo. Recently, however, both in vitro and in
      vivo studies have revealed that soluble, oligomeric forms of Abeta also have
      potent neurotoxic activities, and in fact, may be the proximate effectors of the
      neuronal injury and death occurring in AD. A paradigm shift is thus emerging that
      necessitates the reevaluation of the relative importance of polymeric (fibrillar)
      vs. oligomeric assemblies in the pathobiology of AD. In addition to AD, an
      increasing number of neurodegenerative disorders, including Parkinson's disease,
      familial British dementia, familial amyloid polyneuropathy, amyotrophic lateral
      sclerosis, and prion diseases, are associated with abnormal protein assembly
      processes. The archetypal features of the assembly-dependent neuropathogenetic
      effects of Abeta may thus be of relevance not only to AD but to these other
      disorders as well.

PMID- 12210823
TI  - Analysis of neuronal gene expression with laser capture microdissection.
AB  - The brain is a heterogeneous tissue in which the numbers of neurons, glia, and
      other cell types vary among anatomic regions. Gene expression studies performed
      on brain homogenates yield results reflecting mRNA abundance in a mixture of cell
      types. Therefore, a method for quantifying gene expression in individual cell
      populations would be useful. Laser capture microdissection (LCM) is a new
      technique for obtaining pure populations of cells from heterogeneous tissues.
      Most studies thus far have used LCM to detect DNA sequences. We developed a
      method to quantify gene expression in hippocampal neurons from mouse brain using
      LCM and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). This
      method was optimized to permit histochemical or immunocytochemical visualization
      of nerve cells during LCM while minimizing RNA degradation. As an example, gene
      expression was quantified in hippocampal neurons from the Tg2576 mouse model for
      Alzheimer's disease.

PMID- 12210824
TI  - Two separate domains in the golli myelin basic proteins are responsible for
      nuclear targeting and process extension in transfected cells.
AB  - The golli products of the myelin basic protein (MBP) gene are expressed in
      neurons and oligodendrocytes (OLs). In certain neuronal populations, golli
      proteins undergo translocation between the nucleus and cytoplasm/processes during
      development. The proteins consist of two domains, a golli domain of 133 amino
      acids and an MBP domain of variable length. One objective of this study was to
      identify the sequences responsible for nuclear targeting. Site-directed
      mutagenesis and deletion analyses were used to generate a series of golli-green
      fluorescent protein (GFP) DNA constructs that were transfected into OL and
      neuronal cell lines to follow localization by confocal microscopy. The results
      indicated that a 36-residue stretch in the MBP domain is essential for nuclear
      targeting, and the sequence appears to be a nontraditional localization signal
      motif. The studies also revealed that overexpression of golli proteins could
      induce dramatic changes in cell morphology. In OL lines, overexpression of intact
      golli proteins, or golli peptide alone, caused an increase in the length and
      number of processes, and the elaboration of membrane sheets. In the neuronal
      lines, there was a dramatic increase in number and length of extensions. The
      results, consistent with the timing of golli expression in cells during neural
      development, suggest that golli proteins may be involved in process
      formation/extension in OLs and neurons during development. These studies have
      defined two functional domains in the golli protein. Sequences in the MBP domain
      target the protein into the nucleus and sequences within the golli domain induce
      process sheet extension in OLs and neurons.

PMID- 12210825
TI  - Hepatocyte growth factor stimulates the proliferation and migration of
      oligodendrocyte precursor cells.
AB  - Hepatocyte growth factor (HGF) was initially identified as a potent mitogen for
      mature hepatocytes and has since been found to affect a variety of cells.
      Evidence suggests that HGF may also influence the nervous system, in that HGF
      stimulates the proliferation of myelin-forming Schwann cells and olfactory
      ensheathing cells. However, it is not known whether HGF influences
      oligodendrocytes. To address this issue, oligodendrocyte precursors were obtained
      from neonatal rat cerebra and cultured. Immunostaining and Western blotting
      revealed expression of both HGF and the HGF receptor (c-Met) by cultured
      oligodendrocytes. When the ability of HGF to stimulate oligodendrocyte division
      and migration was examined, we observed that treatment with HGF (10-50 ng/ml)
      elicited twofold increases in oligodendrocyte precursor proliferation. HGF also
      enhanced oligodendrocyte precursor migration, with 2.5-fold increases in rates of
      migration seen after treatment for 8 hr. HGF also influenced inducing the
      oligodendrocyte cytoskeleton by altering patterns of F-actin and beta-tubulin
      distribution and enhanced the expression of actin and beta-tubulin. These
      observations show that a functional HGF/c-Met system is present in
      oligodendrocytes, which can influence the growth, development, and cytoskeletal
      organization of oligodendrocytes.

PMID- 12210826
TI  - Interferon-gamma acutely induces calcium influx in human microglia.
AB  - The acute actions of the cytokine, interferon-gamma (IFN-gamma), on intracellular
      calcium [Ca(2+)](i) levels in human microglia were investigated. In the presence
      of a calcium-containing physiological solution (Ca(2+)-PSS), IFN-gamma caused a
      progressive increase in [Ca(2+)](i) to a plateau level with a mean rate of
      increase of 0.81 +/- 0.17 nM/s and mean amplitude of 102 +/- 12 nM (n = 67
      cells). Washout of the cytokine did not alter the plateau established with IFN
      gamma in Ca(2+)-PSS; however, introduction of a Ca(2+)-free PSS diminished
      [Ca(2+)](i) to baseline levels. The decrease in [Ca(2+)](i) with Ca(2+)-free PSS
      would indicate that the response to IFN-gamma was mediated by an influx pathway.
      This result was confirmed in separate experiments showing the lack of an induced
      change in [Ca(2+)](i) with IFN-gamma applied in Ca(2+)-free PSS. The increase in
      [Ca(2+)](i) induced in Ca(2+)-PSS was reduced to near baseline levels when the
      external solution contained low Cl(-) in the maintained presence of IFN-gamma
      suggesting that cellular depolarization inhibited the cytokine mediated entry
      pathway. The compound SKF96365, which blocks store operated influx of Ca(2+) in
      human microglia, was ineffective in altering the increase in [Ca(2+)](i),
      however, La(3+) completely inhibited the Ca(2+) response induced by IFN-gamma.
      Whole-cell patch clamp studies showed no effect of IFN-gamma to alter outward
      currents and inward rectifier K(+) currents. The influx of Ca(2+) may serve a
      signaling role in microglia linking IFN-gamma to functional responses of the
      cells to infiltrating T lymphocytes into the central nervous system (CNS) during
      inflammatory processes.

PMID- 12210827
TI  - Characterization of neuronal death induced by focally evoked limbic seizures in
      the C57BL/6 mouse.
AB  - Research into the molecular mechanisms of epileptic brain injury is hampered by
      the resistance of key mouse strains to seizure-induced neuronal death evoked by
      systemically administered excitotoxins such as kainic acid. Because C57BL/6 mice
      are extensively employed as the genetic background for transgenic/knockout
      modeling in cell death research but are seizure resistant, we sought to develop a
      seizure model in this strain characterized by injury to the hippocampal CA
      subfields. Adult male C57BL/6 mice underwent focally evoked seizures induced by
      intraamygdala microinjection of kainic acid. Kainic acid (KA) effectively
      elicited ipsilateral CA3 pyramidal neuronal death within a narrow dose range of
      0.1-0.3 microg, with mortality < 10%. With employment of the most consistent (0.3
      microg) dose, seizures were terminated 15, 30, 60, or 90 min after KA by
      diazepam. Damage was largely restricted to the ipsilateral CA3 subfield of the
      hippocampus, but injury was also consistent within CA1, suggesting that this
      mouse model better reflects the hippocampal neuropathology of human temporal lobe
      epilepsy than does the rat, in which CA1 is typically spared. Confirming this CA1
      injury as seizure specific and not a consequence of ischemia, we used laser
      Doppler flowmetry to determine that cerebral perfusion did not significantly
      change (97% to 118%) over control. Degenerating cells were > 95% neuronal as
      determined by neuron-specific nuclear protein (NeuN) counterstaining of terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeled (TUNEL) brain
      sections. Furthermore, TUNEL-positive cells often exhibited the morphological
      features of apoptosis, and small numbers were positive for cleaved caspase-3.
      These data establish a mouse model of focally evoked seizures in the C57BL/6
      strain associated with a restricted pattern of apoptotic neurodegeneration within
      the hippocampal subfields that may be applied to research into the molecular
      basis of neuronal death after seizures.

PMID- 12210828
TI  - Gene transfer of glial cell-derived neurotrophic factor and cardiotrophin-1
      protects PC12 cells from injury: involvement of the phosphatidylinositol 3-kinase
      and mitogen-activated protein kinase kinase pathways.
AB  - Gene therapy for neurodegenerative diseases may utilize the expression of
      neurotrophic factors because of their potential to promote survival and
      regeneration of injured neuronal cells. Increasing numbers of these factors are
      being considered for gene transfer, but their specificity and efficacy in
      neuroprotection are greatly variable. The major aims of this study were to carry
      out gene transfer of various neurotrophic factors and investigate their
      mechanisms of action as well as their protective effects on the viability of rat
      pheochromocytoma (PC12) cells. We used glutamate, S-nitroso-N-acetyl-DL
      penicillamine (SNAP), and staurosporine to induce excitatory damage, oxidative
      stress, and apoptosis, respectively, because these mechanisms are thought to
      participate in various disease processes leading to degeneration of cells. We
      utilized adenovirus vectors for efficient gene transfer of trophic factors (glial
      cell derived neurotrophic factor [GDNF] and cardiotrophin-1 [CT-1]) or calbindin
      D28k. We found that GDNF and CT-1 gene transfers were equally effective in saving
      PC12 cells from injury, but calbindin expression did not show any beneficial
      effects. GDNF gene transfer was much more efficient in protecting PC12 cells from
      damage than direct GDNF administration. The protection by GDNF expression against
      staurosporine was mediated through both phosphatidylinositol 3-kinase (PI3K) and
      mitogen-activated protein kinase kinase (MAPK kinase; MEK) pathways, but only the
      MEK pathway was involved in the protection against SNAP. In contrast, the
      protective effect of GDNF against glutamate toxicity was independent of these RET
      dependent signal transduction pathways.

PMID- 12210829
TI  - Long-term lithium treatment prevents neurotoxic effects of beta-bungarotoxin in
      primary cultured neurons.
AB  - Lithium is the most commonly used drug for the treatment of manic-depressive
      illness. The precise mechanisms underlying its clinical efficacy remain unknown.
      In this study, we found that long-term exposure to lithium chloride protected
      cultured cerebellar granule neurons (CGNs) against beta-bungarotoxin (beta-BuTX)
      induced neurotoxicity. This neuroprotection was exhibited at the therapeutically
      relevant concentration of 1.2 mM lithium. Pretreatments for 3-5 days (long-term)
      were required for protection to occur; but a 3 hr treatment (short-term) was
      ineffective. In contrast, a longer treatment for 6-7 days or a higher
      concentration of 3 mM lithium led not only to loss of the neuroprotective effect
      but also to a neurotoxic effect. These findings suggest that lithium protection
      is limited to its narrow window of concentration and apparently relevant to its
      narrow therapeutic index in clinical application. Measurement of intracellular
      calcium [Ca(2+)](i) revealed that neurotoxic concentrations of beta-BuTX markedly
      increased [Ca(2+)](i), which could be attenuated by long-term, but not short
      term, lithium treatment. Thus, the protection induced by lithium in CGNs was
      attributed to its inhibition of calcium overload. In addition, the Ca(2+)
      signaling pathway, including reactive oxygen species production and mitochondrial
      membrane potential reduction, along with the neurotoxic effect of beta-BuTX was
      blocked by long-term, but not short-term, lithium treatment. All of these results
      indicate that a crucial step for lithium protection is modulation of [Ca(2+)](i)
      homeostasis and that lithium neurotoxicity possibly, at least in part, is due to
      calcium overload. In conclusion, our results suggest that lithium, in addition to
      its use in treatment of bipolar depressive illness, may have an expanded use in
      intervention for neurotoxicity.

PMID- 12210830
TI  - Malignant rhabdoid tumor shows incomplete neural characteristics as revealed by
      expression of SNARE complex.
AB  - To elucidate the biological differences in neural phenotype between malignant
      rhabdoid tumor (MRT) and neuroblastoma cell lines, we examined the expression of
      solube N-ethylmaleimide-sensitive fusion protein attachment protein receptor
      (SNARE) complex proteins in MRT cell lines under differentiation induction with
      12-O-tetradecanoylphorbol-13-acetate (TPA). Six MRT cell lines (TM87-16, STM91
      01, TTC642, TTC549, YAM-RTK1, and TTC1240) and six neuroblastoma cell lines (IMR
      32, NH12, SCCH26, TGW, NB-1, and NB-NR) were used in this study. Expression of
      SNAREs: the vesicle SNARE (synaptotagmin, synaptophysin, and synaptobrevin-2) and
      the target SNARE (syntaxin 1A, SNAP-25A/B) was examined. Our results showed that
      in MRT cells, only two cell lines (TM87-16, TTC642) expressed the vesicle SNARE
      and the target SNARE with the exception of SNAP-25B, while all neuroblastoma
      cells expressed the entire SNARE complex. During differentiation, synaptotagmin
      was upregulated in these two MRT cell lines. Interestingly, synaptophysin was
      downregulated in these MRT cell lines in contrast with the neuroblastoma cell
      lines. SNAP-25B was not expressed in MRT cells after differentiation with TPA.
      MRT cells having a neural phenotype morphologically looked like neuroblastoma
      cells after treatment with TPA. However, the expression of SNARE complex was
      incomplete in MRT cells. Our results suggest that the biological characteristics
      of MRT cells with neural phenotype are distinct from those of neuroblastoma
      cells.

PMID- 12210831
TI  - Role of low-affinity p75 receptor in nerve growth factor-inducible growth arrest
      of PC12 cells.
AB  - Mutant PC12 cell clones (PC84 cells) were obtained by transfection with nerve
      growth factor (NGF) cDNA. These cells secreted active NGF, extended short
      processes, and proliferated faster than the parental PC12 cells. These features
      are of great interest because the parental PC12 cells cease proliferation and
      extend long processes when transfected with NGF cDNA. PC84 cells expressed a high
      level of acetylcholinesterase activity and neurofilament M, which indicates that
      PC84 cells were differentiated. The inhibition of TrkA by K252a diminished the
      short processes of PC84 cells but had no effect on their fast proliferation. The
      expression level of TrkA in PC84 cells was comparable to that in PC12 cells;
      whereas that of another NGF receptor, p75, was significantly lower. These data
      suggest that the decrease of p75 contributed to the continuous growth of PC84
      cells, which was confirmed by suppressing p75 activity of PC12 cells with the
      antisense oligonucleotide of p75 or with anti-p75 neutralizing antibody. The
      treated cells did not cease proliferation in the presence of NGF and extended
      short processes. Our results suggest that NGF signaling via TrkA affects the
      differentiation characteristics of PC12 cells but that an additional signaling
      via p75 is necessary for the growth arrest of the cells.

PMID- 12210832
TI  - Alterations in matrix metalloproteinase-9 levels and tissue inhibitor of matrix
      metalloproteinases-1 expression in a transforming growth factor-beta transgenic
      model of hydrocephalus.
AB  - The development of spontaneous hydrocephalus in mouse models resulting from the
      overexpression of transforming growth factor-beta (TGFbeta-1) has been previously
      described, although the mechanism by which this occurs remains obscure. It has
      been previously demonstrated that increased expression of TGFbeta has
      consequences for the levels of matrix metalloproteinases (MMPs) and their
      specific inhibitors (tissue inhibitors of MMPs, or TIMPs). These remodeling
      proteins play an important role in extracellular matrix (ECM) maintenance through
      degradation and deposition of ECM components. The present study investigated the
      relationship between elevated levels of TGFbeta-1, the ECM modulators TIMP-1 and
      MMP-9, and development of hydrocephalus in the neonatal mouse. In newborn pups,
      TIMP-1 mRNA levels were equal between animals expressing the TGFbeta-1 transgene
      and littermates without the transgene. However, immunohistochemistry of
      littermate pups shows that the distribution of TIMP-1 was changed from
      homogeneous with large punctate concentrations of signal to uniform, dense
      staining in hydrocephalic animals carrying the TGFbeta-1 transgene. The mRNA
      levels of MMP-9 were decreased in the transgenic animals, as were the activity
      levels MMP-9. These results suggest that the remodeling protein MMP-9 and its
      specific inhibitor, TIMP-1, may contribute to the spontaneous development of
      hydrocephalus in this transgenic model by altering the ECM environment.

PMID- 12210833
TI  - Characterization of cholera toxin B subunit-induced Ca(2+) influx in
      neuroblastoma cells: evidence for a voltage-independent GM1 ganglioside
      associated Ca(2+) channel.
AB  - The role of endogenous GM1 ganglioside in neurite outgrowth has been studied in
      N18 and NG108-15 neuroblastoma cells with the GM1-specific ligand cholera toxin B
      subunit (Ctx B), which stimulates Ca(2+) influx together with neuritogenesis. Our
      primary goal has been to identify the nature of the calcium channel that is
      modulated by GM1. An L-type voltage-operated Ca(2+) channel (VOCC) was previously
      proposed as the mediator of this phenomenon. This investigation, employing fura-2
      fluorescent measurements and specific channel blockers and other agents, revealed
      that GM1 modulates a hitherto unidentified Ca(2+) channel not of the L type. It
      was opened by Ctx B; was permeable to Ca(2+) and Ba(2+) but not Mn(2+); and was
      blocked by Ni(2+), Cd(2+), and La(3+). Although most dihydropyridines inhibited
      Ctx B-induced Ca(2+) influx as well as neurite outgrowth at higher
      concentrations, they and other VOCC blockers at normally employed concentrations
      failed to do so, suggesting uninvolvement of VOCC. In addition, Ca(2+) influx
      induced by Ctx B was not mediated by cGMP-dependent or G-protein-coupled
      nonselective cation channels, as demonstrated by the cGMP antagonist Rp-cGMPS or
      the G-protein/receptor uncoupling agent suramin, respectively. Finally, Ca(2+)
      influx was unlikely to be due to inhibition or reversal of Na(+)-Ca(2+) exchanger
      via Ctx B induction of Na(+) uptake, insofar as no effect was seen on blocking
      Na(+) channels, inhibiting Na(+)-K(+)-ATPase, or eliminating extracellular Na(+).
      The results suggest that this novel channel is gated by interaction with GM1,
      which, when associated with the channel and bound by appropriate ligand, promotes
      Ca(2+) influx. This in turn induces signaling for the onset of neuritogenesis.

PMID- 12210834
TI  - Postnatal development of 11beta-hydroxysteroid dehydrogenase type 1 in the rat
      hippocampus.
AB  - Glucocorticoids (GCs) have important actions in the hippocampus of the brain,
      where their access to glucocorticoid receptor (GR) is increased by 11beta
      hydroxysteroid dehydrogenase type 1 (11beta-HSD1). 11beta-HSD1 converts
      biologically inactive 11-dehydrocorticosterone into active corticosterone.
      However, the postnatal development of 11beta-HSD1 in the hippocampus is not
      properly understood. In this study, the postnatal distribution and development of
      11beta-HSD1 in the hippocampus of the rat brain was studied with
      immunohistochemistry and Western blot analysis. Results showed that abundant
      11beta-HSD1 immunoreactive substance (ir-11beta-HSD1) was present in the
      hippocampus. There were homogeneous distributions of 11beta-HSD1 in the
      hippocampal CA1, CA2, CA3, CA4 regions and the dentate gyrus at postnatal days 1,
      3, and 7. Interestingly, the developmental distribution of GR in the hippocampus
      followed the same pattern as 11beta-HSD1. Western blot analysis demonstrated that
      a higher level of expression of 11beta-HSD1 in the hippocampus was found in the
      first 2 weeks of life. The expressions of 11beta-HSD1 started to drop to adult
      levels at about postnatal day 15 both in the hippocampus and in other brain
      areas. These results suggest that the higher expression of 11beta-HSD1 in the
      neonatal hippocampus may be important for the maturation of the central nervous
      system mediated by GCs through GR.

PMID- 12210835
TI  - Human bone marrow stromal cell cultures conditioned by traumatic brain tissue
      extracts: growth factor production.
AB  - Treatment of traumatic brain injury (TBI) with bone marrow stromal cells (MSCs)
      improves functional outcome in the rat. However, the specific mechanisms by which
      introduced MSCs provide benefit remain to be elucidated. Currently, the ability
      of therapeutically transplanted MSCs to replace injured parenchymal CNS tissue
      appears limited at best. Tissue replacement, however, is not the only possible
      compensatory avenue in cell transplantation therapy. Various growth factors have
      been shown to mediate the repair and replacement of damaged tissue, so trophic
      support provided by transplanted MSCs may play a role in the treatment of damaged
      tissue. We therefore investigated the temporal profile of various growth factors,
      brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular
      endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and
      hepatocyte growth factor (HGF), within cultures of human MSCs (hMSCs) conditioned
      with cerebral tissue extract from TBI. hMSCs were cultured with TBI extracts of
      rat brain in vitro and quantitative sandwich enzyme-linked immunosorbent assays
      (ELISAs) were performed. TBI-conditioned hMSCs cultures demonstrated a time
      dependent increase of BDNF, NGF, VEGF, and HGF, indicating a responsive
      production of these growth factors by the hMSCs. The ELISA data suggest that
      transplanted hMSCs may provide therapeutic benefit via a responsive secretion of
      an array of growth factors that can foster neuroprotection and angiogenesis.

PMID- 12210836
TI  - Metabolic changes in the cerebrospinal fluid of patients with lumbar disc
      herniation or spinal stenosis.
AB  - Metabolite levels in cerebrospinal fluid from patients with lower back pain
      and/or sciatica caused by disc herniation or spinal stenosis were compared with
      levels in pain-free controls using proton magnetic resonance spectroscopy.
      Significant differences for several metabolites were found in patients with pain
      compared with controls. Most changes were found in the group with disc
      herniation, including reductions in glucose, alanine, and lactate, suggesting
      increased aerobic metabolism in this group. There was a significant reduction in
      the level of glucose in the group with spinal stenosis irrespective of whether
      the patients were compared with the whole control group (age-weighted) or with
      age-matched controls. Additionally, inositol and creatinine were reduced in
      patients with disc herniation. Inositol was also significantly reduced in the
      spinal stenosis group when age matched to controls. Insofar as the levels of pain
      recorded by the patients with lumbar pathology were similar in the two groups, it
      seems more likely that the reductions in metabolite levels recorded in the group
      with disc herniations are related to disc pathology rather than the perception of
      pain. However, the possibility that pain perception contributes to the metabolic
      changes cannot be excluded.

PMID- 12210837
TI  - Developmentally regulated changes in cellular compartmentation and synaptic
      distribution of actin in hippocampal neurons.
AB  - Actin dynamics and actin-based motility are important for neurite outgrowth and
      synapse plasticity. Recent work implicates actin in synapse assembly, but the
      morphological relationship between actin and synapses during development is
      unclear. Here we used developing hippocampal neurons grown in culture to examine
      the relationship between F- and G-actin and clusters of synaptic proteins. Both F
      and G-actin are most enriched in dendritic and axonal growth cones, but only G
      actin is present within the distal tips of filopodia. Outside of growth cones, F
      actin levels are greater in dendrites than in axons, whereas G-actin levels are
      slightly greater in axons than in dendrites. The distribution of both F- and G
      actin is consistent with their presence at synapses, but only F-actin levels
      become detectably enhanced at synaptic sites. Quantitative analyses suggest that
      first-forming synapses are associated with enhanced levels of pre- and
      postsynaptic F-actin that do not necessarily remain elevated during synapse
      maturation. However, nearly all mature excitatory synapses become associated with
      high, mostly postsynaptic concentrations of F-actin contained principally within
      dendritic spines. Mature shaft and GABAergic synapses are also associated with
      enhanced levels of F-actin, but to a lesser degree. Thus, although F-actin is
      essential for function and maintenance of young synapses, it need not be highly
      concentrated at every site. The large increase in postsynaptic F-actin
      concentration observed in mature neurons is likely to reflect actin's role in
      dendritic spine morphology and in synapse plasticity.

PMID- 12210838
TI  - Single-chain variable fragment antibodies against the neural adhesion molecule
      CHL1 (close homolog of L1) enhance neurite outgrowth.
AB  - The neural cell adhesion molecule CHL1 (close homolog of L1) plays important
      roles in neurite outgrowth and neuronal survival in vitro. Reproducible and
      functionally active CHL1 antibodies are critical for a better understanding of
      the functional properties of CHL1 in vitro and in vivo. We have isolated human
      single-chain variable fragment (scFv) antibodies against mouse CHL1 from a human
      synthetic phage display library. To improve the binding activity of such
      antibodies, a clone (C12) was selected for affinity maturation by combined random
      mutagenesis of the V(H) gene and site-directed cassette mutagenesis to introduce
      random mutations in the complementarity determining region 3 (CDR3) of the V(L)
      gene. From the mutant phage display library, we selected a clone (6C2) that gave
      the strongest signal as determined by ELISA. The dissociation constant of 6C2 (Kd
      2.28 x 10(-8) M) was increased approximately 85-fold compared with the wild-type
      clone C12 (Kd 1.93 x 10(-6) M). 6C2 detected CHL1 by Western blot analysis in
      mouse brain homogenates and detected CHL1 in CHL1-transfected cells by
      immunofluorescence. Furthermore, the wild-type and affinity-matured antibodies
      promoted neurite outgrowth of hippocampal and cerebellar neurons in vitro. Our
      results suggest that the affinity-matured CHL1 scFv antibody will serve a range
      of applications in vitro and in vivo.

PMID- 12210839
TI  - Evidence for a role of the N-terminal domain in subcellular localization of the
      neuronal connexin36 (Cx36).
AB  - The expression and functional properties of connexin36 (Cx36) have been
      investigated in two neuroblastoma cell lines (Neuro2A, RT4-AC) and primary
      hippocampal neurons transfected with a Cx36-enhanced green fluorescent protein
      (EGFP) expression vector. Transfected cells express Cx36-EGFP mRNA, and Cx36-EGFP
      protein is localized in the perinuclear area and cell membrane. Upon
      differentiation of cell lines, Cx36-EGFP protein was detectable in processes with
      both axonal and dendritic characteristics. Small gap junction plaques were found
      between adjacent cells, and electrophysiological recordings demonstrated that the
      electrical properties of these gap junctions were virtually indistinguishable
      from those reported for native Cx36. Mutagenesis of Cx36 led to the
      identification of a structural element that interferes with normal protein
      localization. In contrast, site directed mutagenesis of putative protein
      phosphorylation motifs did not alter subcellular localization. This excludes
      phosphorylation/dephosphorylation as a major regulatory step in Cx36 protein
      transport.

PMID- 12210840
TI  - Differential lineage restriction of rat retinal progenitor cells in vitro and in
      vivo.
AB  - To identify and characterize the lineage potential of rat neural retina
      progenitor cells (NRPCs) in vitro and engrafted into rats with retinal
      degeneration, NRPCs were isolated from neural retinas of embryonic day 17 Long
      Evans rats and cultured in serum-free or serum-containing media with fibroblast
      growth factor 2 and neurotrophin 3. After expansion, cellular differentiation was
      initiated by the withdrawal of these growth factors. Despite forming primary
      neurospheres, NRPCs cultured in serum-free medium survived poorly after passage.
      In contrast, NRPCs cultured in serum-containing medium could be expanded for up
      to 12 passages and differentiated into glial fibrillary acidic protein-positive
      glial cells and retina-specific neurons expressing rhodopsin, S-antigen,
      calbindin, recoverin, and calretinin. For in vivo analysis, passage 1 (P1)
      undifferentiated NRPCs were labeled with bromodeoxyuridine (BrdU), implanted into
      the subretinal space of Royal College of Surgeons (RCS) rats, and analyzed
      immunohistochemically 4 weeks postgrafting. The grafted NRPCs showed extensive
      glial differentiation, irrespective of their topographic localization. A few BrdU
      labeled grafted NRPCs expressed protein kinase C, a marker for bipolar and
      amacrine interneuron-specific differentiation. Other retina-specific or
      oligodendrocytic differentiation was not detected in the grafted cells. Although
      NRPCs are capable of self-renewal and multilineage differentiation in vitro, they
      developed mostly into glial cells following engraftment into the adult retina.
      These data suggest that the adult retina retains epigenetic signals that are
      either restrictive for neuronal differentiation or instructive for glial
      differentiation. Induction of lineage-specific cell differentiation of engrafted
      NRPCs to facilitate retinal repair will likely require initiation of specific
      differentiation in vitro prior to grafting and/or modification of the host
      environment concomitantly with NRPC grafting.

PMID- 12210841
TI  - Syndecan-3 and perlecan are differentially expressed by progenitors and mature
      oligodendrocytes and accumulate in the extracellular matrix.
AB  - Oligodendrocyte progenitors originate in the subventricular zone, proliferate,
      migrate to their final destinations, differentiate, and interact with axons to
      produce multilamellar myelin sheaths. These processes are regulated by a variety
      of environmental signals, including growth factors, the extracellular matrix, and
      adhesion molecules. Heparan sulfate proteoglycans are premier candidates as
      participants in this regulation by virtue of their structural diversity and their
      capacity to function as coreceptors for both growth factors and extracellular
      matrix molecules. Consistently with this, we have previously shown that
      oligodendrocyte progenitors are unable to proliferate in response to fibroblast
      growth factor-2 (FGF-2) in the absence of sulfated heparan sulfate proteoglycan.
      Here we show that members of three families of heparan sulfate proteoglycans,
      syndecan, perlecan, and glypican, are developmentally and posttranscriptionally
      regulated during oligodendrocyte-lineage progression: Syndecan-3 is synthesized
      by oligodendrocyte progenitors (but not terminally differentiated
      oligodendrocytes) and is up-regulated by FGF-2; perlecan synthesis increases as
      oligodendrocytes undergo terminal differentiation; glypican-1 is expressed by
      both progenitors and differentiated oligodendrocytes. Astrocytes express glypican
      1 and perlecan but not syndecan-3. All three of these heparan sulfate
      proteoglycans are shed from the cell surface and bind to specific substrates. The
      developmentally regulated expression of these heparan sulfate proteoglycans is
      indicative of their participation in events involving growth factor receptors and
      the extracellular matrix that may regulate oligodendrocyte progenitor
      proliferation, migration, and adhesion phenomena.

PMID- 12210842
TI  - Molecular mechanisms involved in the actions of apotransferrin upon the central
      nervous system: Role of the cytoskeleton and of second messengers.
AB  - Apotransferrin (aTf), intracranially administered into newborn rats, produces
      increased myelination with marked increases in the levels of myelin basic protein
      (MBP), phospholipids and galactolipids, and mRNAs of MBP and 2', 3' cyclic
      nucleotide 3'-phosphohydrolase (CNPase). Cytoskeletal proteins such as tubulin,
      actin, and microtubule-associated proteins are also increased after aTf
      injection. In contrast, almost no changes are observed in myelin proteolipid
      protein (PLP) or in its mRNA or cholesterol. In the present study, we used brain
      tissue slices and cell cultures highly enriched for oligodendroglia to
      investigate signaling pathways involved in the action of aTf, and to find out
      whether cytoskeletal integrity and dynamics were essential for its action upon
      the neural expression of certain genes. Treatment of brain-tissue slices with aTf
      produced a marked increase in the expression of MBP, CNPase, and tubulin mRNAs.
      Colchicine, cytochalasin, and taxol severely reduced the effect of aTf. Addition
      to cultures of an antibody against transferrin receptor (TfR), protein kinase
      inhibitors, or a cyclic AMP (cAMP) analogue showed that a functionally intact TfR
      was necessary, and that tyrosine kinase, protein kinase C and A, as well as
      calcium-calmodulin-dependent kinase (Ca-CaMK) activities appeared to mediate aTf
      actions upon the expression of the above mentioned genes. Changes in the levels
      of phosphoinositides and cAMP induced by aTf in oligodendroglial cell (OLGc)
      cultures correlated with these results and coincide with an activation of the
      cyclic response element binding protein (CREB) and of mitogen activated protein
      kinases. The increased expression of certain myelin genes produced by aTf appear
      to be mediated by interaction of this glycoprotein with its receptor, by the
      cytoskeleton of the OLGc, and by a complex activation of protein kinases which
      lead to CREB phosphorylation.

PMID- 12210843
TI  - Comparative analysis of Schwann cell lines as model systems for myelin gene
      transcription studies.
AB  - Primary and immortalized cultured Schwann cells are commonly utilized in analyses
      of myelin gene promoters, but few lines are well-characterized in terms of their
      endogenous expression of myelin genes. This is particularly significant in that
      cultured Schwann cells typically do not express myelin genes at levels comparable
      to those observed in vivo. In this study, the steady-state levels of mRNA and
      protein for five Schwann cell markers (PMP22, P0, MBP, MAG, and LNGF-R) were
      assessed in primary Schwann cells and six representative Schwann cell lines (RT4
      D6P2T, JS-1, RSC96, R3, S16, and S16Y). RT4-D6P2T and S16 cells were the most
      similar to myelinating Schwann cells based on their comparatively high expression
      of PMP22 and P0 mRNA. Both RT4-D6P2T and S16 also expressed P0 protein. In
      addition, the previously reported P1-A positive regulatory region from the
      myelination-specific PMP22 promoter demonstrated significant activity in both
      these cell lines. However, nuclear proteins that interacted with P1-A were
      different in extracts prepared from RT4-D6P2T and S16 cells. Primary Schwann
      cells expressed myelin proteins at levels that were equal or less than those
      observed with the RT4-D6P2T and S16 lines, indicating that primary Schwann cells
      are not necessarily better than immortalized Schwann cells as model systems for
      the study of myelin gene regulation. The data presented here demonstrate that
      cultured Schwann cells used to study myelin gene promoters have to be carefully
      selected on the basis of the endogenous level of expression of the myelin gene
      under study.

PMID- 12210844
TI  - Androgen receptor messenger RNA and protein in adult rat sciatic nerve:
      implications for site of androgen action.
AB  - Gonadal androgens exert a wide variety of effects on several neuromuscular
      systems, including controlling the developmental fate of motoneurons and
      neuromuscular synapses and promoting the growth of adult dendrites and axons.
      Paramount in understanding the molecular mechanisms behind androgen action is
      determining where androgen acts; does androgen act directly or indirectly on
      cells to change their fate and function? One step toward answering this question
      has been to determine which cells express androgen receptors (ARs). Motoneurons
      and skeletal muscles both have ARs and are, therefore, potential sites of
      androgen action. Recent evidence indicates that the sciatic nerve in rats also
      contains AR mRNA (Magnaghi et al. [1999] Brain Res. Mol. Brain Res. 70:36-44),
      although which cell type expresses ARs remains unanswered. In this study, we
      explored the question of which cell populations in the rat sciatic nerve express
      ARs. Using immunocytochemistry and reverse transcriptase-PCR, we confirmed the
      presence of AR protein and mRNA in sciatic nerve from adult rats and found a sex
      difference, favoring males, in the number of cell nuclei immunopositive for AR.
      This difference was not due to a sex difference in the overall number of cell
      nuclei. We also found a difference favoring males in AR mRNA, evidence also
      suggesting that AR expression is higher in males than in females. Results from
      double-immmunolabeling experiments in sciatic nerve from adult males suggest
      that, within the endoneurial compartment, endoneurial fibroblasts stain
      prominently for AR, with some endothelial cells also AR(+). Although Schwann
      cells showed light AR immunostaining, this staining is apparently nonspecific. We
      conclude that cells within peripheral nerve have ARs and may, therefore, mediate
      some of the effects of androgens on neuromuscular systems.

PMID- 12210845
TI  - S-adenosyl-methionine-induced apoptosis in PC12 cells.
AB  - Our previous studies showed that S-adenosyl-methionine (SAM) induced Parkinson's
      disease-like changes in rat. It caused death to dopamine neurons in the
      substantia nigra, which appeared shrunken and fragmented, indicative of apoptosis
      like changes (Charlton and Crowell [1995] Mol. Chem. Neuropathol. 26:269-284;
      Charlton [1997] Life Sci. 61:495-502). In this study, we investigated whether SAM
      causes apoptosis in both undifferentiated PC12 (PC12) cells and nerve growth
      factor (NGF)-differentiated PC12 (D-PC12) cells. S-adenosyl-homocysteine (SAH),
      the nonmethyl analog of SAM, was also tested. SAM and SAH (1.0 nM to 10.0 microM)
      caused lactate dehydrogenase (LDH) release from the PC12 cells and D-PC12 cells;
      cells with morphological changes and fluorescent DNA fragmentation staining were
      detected among both PC12 cell and D-PC12 cell. Compared with the PC12 cell, the D
      PC12 cell, a postmitotic cell, was more sensitive to the toxic effects of SAM or
      SAH and presented much greater LDH release, suggesting a lethal effect;
      surprisingly, the amounts of apoptotic cells did not differ significantly between
      the two kinds of cells. In medium deprived of exogenous methionine, a decline in
      LDH release was observed in PC12 and D-PC12 cells. Also, lower levels of
      intracellular SAM and SAH were observed in the methionine-deleted media, which
      were reversed by the addition of either SAM or SAH. An antivitamin B(12)
      monoclonal antibody was added to methionine-depleted medium, resulting in
      deficiency of both endogenous and exogenous methionine, which caused further
      decreases in LDH release and reduction in the levels of intracellular SAM and
      SAH. The preliminary data showed different sensitivities to SAM or SAH between
      PC12 cell and D-PC12 cells, which suggests that PC12 cell may be more stable as a
      metabolic model. Apoptosis of PC12 cells was also assessed by PARP cleavage
      detection, Western blot analysis of Bax and Bcl-2 proteins, and DNA laddering on
      agarose gel electrophoresis. The proapoptoic protein Bax was dominantly
      expressed, whereas Bcl-2 was slightly down-regulated by SAM. SAH weakly induced
      the expression of Bax and slightly decreased Bcl-2 levels. The effects of SAM and
      its analog, SAH, were demonstrated conclusively to induce apoptosis in PC12
      cells.

PMID- 12210846
TI  - Neurons overexpressing mutant presenilin-1 are more sensitive to apoptosis
      induced by endoplasmic reticulum-Golgi stress.
AB  - Most early-onset cases of familial Alzheimer's disease (FAD) are linked to
      mutations in two related genes, ps1 and ps2. FAD-linked mutant PS1 alters
      proteolytic processing of the amyloid precursor protein and increases
      vulnerability to apoptosis induced by various cell stresses. In transfected cell
      lines, mutations in ps1 decrease the unfolded-protein response (UPR), which is
      the response to the increased amounts of unfolded proteins that accumulate in the
      endoplamic reticulum (ER), indicating that these mutations may increase
      vulnerability to ER stress by altering the UPR signalling pathway. Here we report
      that, in primary cultured neurons from cortices of transgenic mice,
      overexpression of mutated PS1 (M146L mutation) but not PS1 wild-type (wt)
      enhanced spontaneous neuronal apoptosis that involved oxidative stress and
      caspase activation. In PS1M146L cultures, neurons displaying immunoreactivity for
      human PS1 were threefold more vulnerable to spontaneous apoptosis than the
      overall neuronal population. In addition, PS1M146L transgenic neurons were more
      sensitive to apoptosis induced by various stresses, including two ER-Golgi
      toxins, nordihydroguaiatric acid and brefeldin A (also known to induce UPR), as
      well as staurosporine. In contrast, PS1 wt transgenic neurons were resistant to
      apoptosis induced by Golgi-ER toxins but displayed a comparable vulnerability to
      staurosporine. Our study demonstrates that, as previously reported,
      overexpression of FAD-linked mutant PS1 enhances neuronal vulnerability to
      spontaneous and induced apoptosis. In addition, we show that this vulnerability
      was correlated with mutant PS1 protein expression and that PS1 wt overexpression
      selectively prevented ER-Golgi stress-induced apoptosis. These data indicate that
      PS1 interferes with a specific apoptotic pathway that results from a dysfunction
      of the ER-Golgi compartment.

PMID- 12210847
TI  - Cerebral postischemic reperfusion-induced demethylation of the protein
      phosphatase 2A catalytic subunit.
AB  - Brain reperfusion after a period of global ischemia induces changes in the
      phosphorylation state of a great number of proteins. Neuronal responses to
      ischemia and reperfusion are quite different depending on the brain region, and
      phosphorylation changes may be implicated in this tissue-specific response. For
      this reason, we have used both biochemical and immunohistochemical methods to
      investigate the potential role of PP2A, the most abundant Ser/Thr phosphatase in
      the brain, in ischemic injury. PP2A activity as measured with phosphorylase a as
      substrate was slightly inhibited after 30 min ischemia followed by 30 min
      reperfusion, and this inhibition correlated with an increased S6K1 and ERK1/2
      phosphorylation. Using a monoclonal antibody unable to recognize the methylated
      form of PP2Ac, we demonstrated that the catalytic subunit of PP2A (PP2Ac) was
      highly methylated in the brain. In addition, the postischemic reperfusion-induced
      changes in PP2Ac methylation were studied in sections from cerebral cortex,
      hippocampus and striatum. Regional differences in PP2Ac methylation were observed
      within control brains, and the postischemic reperfusion caused a generalized
      demethylation of PP2Ac. Those regions in the control brains containing highest
      levels of methylated PP2Ac were the most intensively demethylated after
      reperfusion and corresponded to the regions most vulnerable to ischemic damage.

PMID- 12210848
TI  - Oxidative stress induced by phenylketonuria in the rat: Prevention by melatonin,
      vitamin E, and vitamin C.
AB  - Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency
      of the phenylalanine hydroxylation system and is characterized by a block in the
      conversion of phenylalanine (PHE) to tyrosine. We examined the effects of
      maternal hyperphenylalaninemia on the morphological and biochemical development
      of pup rat brain and cerebellum. In our model of PKU we evaluated a number of
      markers of oxidative stress such as Ehrlich adducts formation, lipid
      peroxidation, as well as the levels of reduced and oxidized glutathione, and the
      activities of the enzymes glutathione peroxidase and glutathione reductase. We
      also studied the expression of heme-oxigenase-1 and mitogen-activated protein
      kinase 1/2 (MAPK 1/2) as additional markers of oxidative stress. We demonstrate
      that PKU strongly increased most of the oxidative stress markers studied and
      induced significant morphological damage. We also showed that daily
      administration of melatonin (20 mg/kg BW), vitamin E (30 mg/kg BW), and vitamin C
      (30 mg/kg BW) until delivery prevented the oxidative biomolecular damage in the
      rat brain and cerebellum. Although no significant differences were observed among
      the antioxidants studied, it should be noted that the doses of melatonin were
      less than those for vitamins E and C. We conclude that PKU induces a clear state
      of oxidative stress that is somehow involved in the brain and body damage
      occurring in this inborn error. Moreover, melatonin and other antioxidants are
      capable of preventing completely the damage induced by PKU.

PMID- 12210850
TI  - Essential tremor is a monosymptomatic disorder.

PMID- 12210849
TI  - Activation of adenosine triphosphate-sensitive potassium channels confers
      protection against rotenone-induced cell death: therapeutic implications for
      Parkinson's disease.
AB  - It is anticipated that further understanding of the protective mechanism induced
      by ischemic preconditioning will improve prognosis for patients of ischemic
      injury. It is not known whether preconditioning exerts beneficial actions in
      neurodegenerative diseases, in which ischemic injury plays a causative role. Here
      we show that transient activation of ATP-sensitive potassium channels, a trigger
      in ischemic preconditioning signaling, confers protection in PC12 cells and SH
      SY5Y cells against neurotoxic effect of rotenone and MPTP, mitochondrial complex
      I inhibitors that have been implicated in the pathogenesis of Parkinson's
      disease. The degree of protection is in proportion to the bouts of exposure to an
      ATP-sensitive potassium channel opener, a feature reminiscent of ischemic
      tolerance in vivo. Protection is sensitive to a protein synthesis inhibitor,
      indicating the involvement of de novo protein synthesis in the protective
      processes. Pretreatment of PC12 cells with preconditioning stimuli FeSO(4) or
      xanthine/xanthine oxidase also confers protection against rotenone-induced cell
      death. Our results demonstrate for the first time the protective role of ATP
      sensitive potassium channels in a dopaminergic neuronal cell line against
      rotenone-induced neurotoxicity and conceptually support the view that ischemic
      preconditioning-derived therapeutic strategies may have potential and feasibility
      in therapy for Parkinson's disease.

PMID- 12210851
TI  - Essential tremor: a heterogenous disorder.

PMID- 12210852
TI  - Genetics of parkinsonism.
AB  - Parkinson's disease (PD) was noted to have a familial component as early as 1880
      (Leroux, 1880). More recently, the discovery of several genetic factors
      influencing parkinsonism has emphasized the importance of heredity in PD. The
      clinical spectrum of familial parkinsonism is wide; it includes not only PD, but
      also dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP),
      essential tremor, and other disorders. In the general population, it is likely
      that PD results from combined genetic and environmental factors, most of which
      are not yet known. The discovery of causal mutations in the gene for alpha
      synuclein, parkin, and of genetic linkages to chromosomes 2p4, 4p5, and three
      loci on 1q6-8 have revolutionized PD research. This review focuses on recent
      progress in the Mendelian genetics of PD and those diseases in which parkinsonism
      is a prominent feature, and considers how these discoveries modify our beliefs
      regarding the etiology and pathogenesis of these disorders.

PMID- 12210853
TI  - Small-amplitude cortical myoclonus in Parkinson's disease: physiology and
      clinical observations.
AB  - We studied the occurrence of small-amplitude myo- clonus in 20 idiopathic
      Parkinson's disease patients who had no evidence of dementia as defined by
      criteria in the Diagnostic and Statistical Manual of Mental Disorders, fourth
      edition. Parkinson's disease was diagnosed by United Kingdom Brain Bank criteria,
      and clinical assessment was performed with the Unified Parkinson's Disease Rating
      Scale motor score, Hoehn and Yahr staging, and the Mini-Mental State Examination.
      Clinical assessment showed a range of mild-to-moderate disease severity. All
      patients underwent polygraphic electro-encephalographic-electromyographic (EMG)
      recording with back-averaging, somatosensory evoked potential testing, and
      attempted elicitation of long-latency EMG responses. Multichannel surface EMG
      recording during muscle activation showed irregular, multifocal, brief (<50 msec)
      myoclonus EMG discharges. Back-averaging consistently showed a focal, short
      latency, electroencephalographic transient prior to the myoclonus EMG discharge.
      Cortical somatosensory evoked potential waves were not enlarged, and long-latency
      EMG responses at rest were not present. The small-amplitude myoclonus in such
      cases arises from an abnormal discharge from the sensorimotor cortex. The
      mechanism of this cortical myoclonus in Parkinson's disease has differences from
      the more common "cortical reflex myoclonus" physiology. Advanced parkinsonism is
      not a requirement for manifestation of this myoclonus type. Although the
      myoclonus occurred without dementia in these cases, its relationship to the
      subsequent development of cognitive impairment remains to be defined.

PMID- 12210854
TI  - Analysis of sway in Parkinson's disease using a new inclinometry-based method.
AB  - In order to analyze balance control, we developed a new inclinometry-based method
      to provide direct information about body sway in the side-to-side and forward
      backward directions. We tested the clinical utility of this method for analyzing
      balance in Parkinson's disease (PD), and studied the clinical correlates of the
      balance measures in PD. Postural sway was measured during quiet stance with eyes
      open and eyes closed in 28 PD patients and in 32 age- and sex-matched control
      subjects. Postural sway was modeled using side-to-side and forward-backward
      directional sway movements, sway velocity, and sway area. The amount of postural
      sway in the PD patients was greater than in the control subjects, the higher
      level being most marked in patients with severe or long-duration PD. All the side
      to-side directional sway parameters were abnormal in the PD patients compared
      with the control subjects (P < 0.05), whereas the forward-backward directional
      parameters did not differentiate the two groups. The most sensitive measures of
      sway were path length, velocity, and area. The duration and severity of PD seem
      to be particularly associated with the amount of side-to-side directional
      postural sway. This new inclinometric method appears to be useful in quantifying
      postural sway and evaluating balance impairment in PD.

PMID- 12210855
TI  - Clinical, 18F-dopa PET, and genetic analysis of an ethnic Chinese kindred with
      early-onset parkinsonism and parkin gene mutations.
AB  - We report on clinical (18)F-labeled 6-fluorodopa ((18)F-dopa) positron emission
      tomography (PET) and molecular genetic analyses of an ethnic Chinese family in
      which three siblings presented with early-onset Parkinson's disease. As described
      in some parkin patients, neither sleep benefit nor diurnal fluctuation was noted.
      Interestingly, depression, anxiety, and obsessive-compulsive disorders were
      manifest. The (18)F-dopa PET scans showed bilateral presynaptic dopaminergic
      dysfunction without marked lateralization. Molecular genetic analysis showed
      identical chromosome 6 haplotypes inherited by affected subjects, with alternate
      allelic deletions of parkin exons 3 and 4. Furthermore, mRNA analyses identified
      aberrantly spliced parkin transcripts, suggesting that unusual parkin protein
      isoforms may be expressed in the brain and retain some function.

PMID- 12210856
TI  - The effect of quetiapine on psychosis and motor function in parkinsonian patients
      with and without dementia.
AB  - Recently, several small studies have indicated that quetiapine may be useful in
      the treatment of drug-induced psychosis in patients with PD. However, there have
      been questions related to atypical antipsychotic therapy and patient selection
      and how that may affect response and tolerability, especially worsening of the
      motor symptoms of PD. In particular, the presence or absence of dementia seems to
      be important. The aim of this study was to evaluate the effect of quetiapine on
      psychosis and motor symptoms in PD patients with and without dementia. A
      retrospective record review of patient responses to quetiapine was conducted.
      Response of psychosis was assessed through patient and caregiver interviews.
      Motor symptom change in relation to this therapy was assessed by patient and
      caregiver interviews and completion of the motor portion of the Unified
      Parkinson's Disease Rating Scale (UPDRSm). Analysis was performed by comparing
      psychosis and motor feature measures from before and after therapy for the group
      as a whole and for demented and nondemented subgroups, using nonparametric tests
      and Fisher's exact test. Forty-three consecutively treated PD patients were
      evaluated. The mean dose of quetiapine was 54 mg per day and the duration of
      therapy was 10 months. Eighty-one percent of patients demonstrated partial or
      complete amelioration of psychosis. Five patients (13%) experienced a worsening
      of PD motor symptoms, which was corroborated by changes seen in UPDRSm. When the
      group was examined as a whole, no significant change in UPDRSm score was noted.
      When demented (n = 20) and nondemented (n = 19) patients were compared,
      improvement in psychosis occurred in similar numbers of patients, but a
      significant difference in the numbers of patients who experienced a worsening of
      motor symptoms was seen (P < 0.02, Fisher's exact test). All five patients who
      complained of motor worsening were in the demented group. UPDRSm score after
      therapy tended to be worse in the demented group (P = 0.55, Mann-Whitney U test).
      There was no significant change in the levodopa dose. Approximately 80% of
      patients chose to continue therapy. We conclude that quetiapine is effective in
      improving psychosis in approximately 80% of PD patients both with and without
      dementia. Patients with dementia seem to have a higher propensity for worsening
      of motor symptoms.

PMID- 12210857
TI  - Unilateral and bilateral pallidotomy for idiopathic Parkinson's disease: a case
      series of 115 patients.
AB  - Lesioning of the internal pallidum is known to improve the symptoms of idiopathic
      Parkinson's disease (PD) and alleviate dyskinesia and motor fluctuations related
      to levodopa therapy. The benefit obtained contralateral to a single lesion is
      insufficient in some cases when symptoms are bilaterally disabling. However,
      reports of unacceptably high rates of adverse effects after bilateral pallidotomy
      have limited its use in such cases. We report on the outcome of unilateral (UPVP)
      and bilateral (BPVP) posteroventral pallidotomy in a consecutive case series of
      115 patients with PD in the United Kingdom and Australia. After 3 months, UPVP
      resulted in a 27% reduction in the off medication Part III (motor) Unified
      Parkinson's Disease Rating Scale score and abolition of dyskinesia in 40% of
      cases. For BPVP, these figures were increased to 31% and 63%, respectively.
      Follow-up of a smaller group to 12 months found the motor scores to be worsening
      but benefit to dyskinesia and activities of daily living was maintained. Speech
      was adversely affected after BPVP, although the change was small in most cases.
      Unilateral and bilateral pallidotomy can be performed safely without
      microelectrode localisation. Bilateral pallidotomy appears to be more effective,
      particularly in reducing dyskinesia; in our experience, the side effects have not
      been as high as reported by other groups.

PMID- 12210858
TI  - Effects of bilateral stimulation of the subthalamic nucleus in patients with
      severe Parkinson's disease and motor fluctuations.
AB  - We present the efficacy and side effects of bilateral deep brain stimulation
      (DBS) of the subthalamic nuclei (STN) performed with a more simplified surgical
      procedure than described by the Grenoble group. A consecutive series of 26
      patients with advanced and levodopa-responsive Parkinson's disease and motor
      complications was evaluated using the Unified Parkinson's Disease Rating Scale
      (UPDRS) part I-VI, timed tests, and a patient diary for 2 days concerning on-off
      phenomenon and dyskinesias. At 3 months, evaluation of stimulation by the UPDRS
      motor score was performed in a double-blind manner and a significant improvement
      of 57% was found. The results 12 months after surgery off medication showed
      significant improvement in both UPDRS motor score and activities of daily living
      of 64% and, on medication, a significant reduction of 86% in duration of
      dyskinesias and 83% in duration of off-periods. Reduction in medication was less
      than for other groups, probably because we used smaller doses of levodopa before
      the operation. No serious side effects were encountered. When the patients are
      carefully selected and followed up, bilateral DBS of STN is a significant
      progress in treatment of advanced idiopathic Parkinson's disease with levodopa
      induced motor complications.

PMID- 12210859
TI  - Parkinsonism in multiple system atrophy: natural history, severity (UPDRS-III),
      and disability assessment compared with Parkinson's disease.
AB  - We analyzed parkinsonian features in multiple system atrophy (MSA) compared with
      age- and disease duration-matched Parkinson's disease (PD) patients, and assessed
      the applicability of the Unified Parkinson's Disease Rating Scale (UPDRS) -III
      motor scale as a means of rating their severity. Cross-sectional analysis of
      parkinsonism was done using UPDRS-III, International Cerebellar Atatia Rating
      Scale, and disability scales (Hoehn and Yahr [H&A], Schwab and England, Katz and
      Lawton) in 50 unselected MSA patients and in 50 matched PD patients. At symptom
      onset, falls occurred 10 times more frequently in MSA, whereas limb tremor was 10
      times more common in PD. At first visit (10.2 months), hemiparkinsonism and pill
      rolling rest tremor were less common in MSA. Hypomimia, atypical rest, postural
      or action tremor, as well as postural instability were more frequent in MSA. At
      study examination (62.4 months), parkinsonian signs in MSA patients were more
      frequently symmetrical and associated with axial rigidity, antecollis and
      postural instability. A levodopa response of >50% was seen in <10% of MSA
      patients. Modified H&Y stages (3.2 +/- 1.3 vs. 2.2 +/- 0.78) and UPDRS-III scores
      (48.14 +/- 19.5 vs. 31.74 +/- 12.9) were significantly (P = 0.0001) higher in
      MSA. The internal consistency of the UPDRS-III was fair in MSA patients
      (Cronbach's alpha >0.90), and correlated well with marked dependency on the
      Schwab and England and Katz and Lawton scales. Factor structure analysis of UPDRS
      III in MSA showed five clinically distinct subscores accounting for 74% of the
      variance, differing from PD by the dependency of the face-speech and limb
      bradykinesia items and independence of the postural-action tremor from the rest
      tremor items. There was a significant correlation (R(2) = 0.70, P = 0.001)
      between ICARS ataxia and UPDRS-III scores in MSA patients. Results confirm a
      distinct profile of parkinsonism in MSA and greater severity and disability
      compared with PD. It also indicates that the UPDRS-III provides a useful severity
      measure of parkinsonism in MSA, albeit contaminated by additional cerebellar
      dysfunction.

PMID- 12210860
TI  - Evidence for shoulder girdle dystonia in selected patients with cervical disc
      prolapse.
AB  - Some patients with cervical disc herniation suffer from persistent nuchal pain
      and muscle spasms after decompressive surgery despite the lack of clinical and
      radiological signs for actual spinal root compression. Sonographic examination of
      the brain in some of these patients showed increased echogenicity of the
      lentiform nuclei as described in patients with idiopathic dystonia. This has been
      linked to an altered Menkes protein level and copper metabolism. We suggest a
      relationship between persistent nuchal pain after adequate cervical disc surgery
      and dystonic movement disorders. Thirteen patients with persistent nonradicular
      nuchal pain after at least one cervical disc surgery and without evidence of
      continuing spinal root compression and 13 age-matched controls were included. All
      patients had a complete neurological examination, ultrasound, and MRI scan of the
      brain. In addition, Menkes protein mRNA levels of leucocytes were analyzed in
      patients and controls. All patients with persistent nuchal pain exhibited a
      constant tonic unilateral shoulder elevation associated with an ipsilateral
      hypertrophy of the trapezius muscle. Ultrasound examination showed an increased
      echogenicity of the lentiform nucleus in one patient unilaterally and in 10
      patients bilaterally but in none of the controls. On MRI the T2-values of the
      lentiform nuclei were found to be higher in patients exhibiting a
      hyperechogenicity of the lentiform nuclei compared to controls (P = 0.01). In
      addition, Menkes protein mRNA levels were decreased in patients with cervical
      disc herniation (P = 0.03). Clinical, neuroimaging, and biochemical findings of
      this selected patient sample with chronic nuchal pain and muscle spasms after
      cervical disc surgery resemble alterations in patients with idiopathic cervical
      dystonia. This suggests a link between both disorders. A peripheral trauma to the
      nerve roots may precipitate dystonic movements in susceptible patients and
      chronic dystonic muscle contraction would account for the persistent nuchal pain.

PMID- 12210861
TI  - Genetic and clinical heterogeneity in paroxysmal kinesigenic dyskinesia: evidence
      for a third EKD gene.
AB  - Paroxysmal kinesigenic dyskinesia (PKD) is characterised by paroxysms of choreic,
      dystonic, ballistic, or athetoid movements. The attacks typically last seconds to
      minutes in duration and are induced by sudden voluntary movement. PKD loci have
      been identified on chromosome 16. We present the clinical and genetic details of
      two British and an Indian family with PKD. Linkage to the PKD loci on chromosome
      16 has been excluded in one of these families, providing evidence for a third
      loci for PKD. Detailed clinical descriptions highlight the presence of both
      adolescent and infantile seizures in some of the PKD families. This study
      attempts to clarify the relationship of adolescent and infantile seizures to PKD
      and provides evidence that PKD is both genetically and clinically heterogeneous.

PMID- 12210862
TI  - Secondary paroxysmal dyskinesias.
AB  - Paroxysmal dyskinesias (PxDs) are involuntary, episodic movements that include
      paroxysmal kinesigenic (PKD), paroxysmal nonkinesigenic (PNKD), and paroxysmal
      hypnogenic (PHD) varieties. Although most PxDs are primary (idiopathic or
      genetic), we found 17 of our 76 patients with PxD (22%) to have an identifiable
      cause for their PxD (10 men; mean age, 41.4 years). Causes included peripheral
      trauma (in three patients), vascular lesions (in four), central trauma (in four),
      kernicterus (in two), multiple sclerosis (in one), cytomegalovirus encephalitis
      (in one), meningovascular syphilis (in one), and migraine (in one). The latency
      from insult to symptom onset ranged from days (trauma) to 18 years (kernicterus),
      with a mean of 3 years. Nine patients had PNKD, two had PKD, five had mixed
      PKD/PNKD, and one had PHD. Hemidystonia was the most common expression of the
      paroxysmal movement disorder, present in 11 patients. Both of the patients with
      PKD had symptom durations of <5 minutes. Symptom duration ranged from 10 seconds
      to 15 days for PNKD and from 5 minutes to 45 minutes for mixed PKD/PNKD. There
      were no uniformly effective therapies, but anticonvulsant drugs, clonazepam, and
      botulinum toxin injections were the most beneficial. Awareness of the variable
      phenomenology and the spectrum of causes associated with secondary PxD will allow
      for more timely diagnosis and early intervention.

PMID- 12210863
TI  - Adult-onset tic disorders.
AB  - We report on 8 patients with adult-onset motor tics and vocalisations. Three had
      compulsive tendencies in childhood and 3 had a family history of tics or
      obsessive-compulsive behaviour. In comparison with DSM-classified, younger-onset
      Gilles de la Tourette syndrome, adult-onset tic disorders are more often
      associated with severe symptoms, greater social morbidity, a potential trigger
      event, increased sensitivity, and poorer response to neuroleptic medication.

PMID- 12210864
TI  - Levodopa-responsive rubral (Holmes') tremor.

PMID- 12210870
TI  - Riluzole prolongs survival time and alters nuclear inclusion formation in a
      transgenic mouse model of Huntington's disease.
AB  - Glutamate excitotoxicity has been suggested to contribute to the pathogenesis of
      Huntington's disease (HD). Riluzole is a substance with glutamate antagonistic
      properties that is used for neuroprotective treatment in amyotrophic lateral
      sclerosis and which is currently tested in clinical trials for treatment of HD.
      R6/2 transgenic mice, which express exon 1 of the human HD gene with an expanded
      CAG triplet repeat, serve as a well-characterized mouse model for HD with
      progressing neurological abnormalities and limited survival. We treated R6/2 HD
      transgenic mice with riluzole orally beginning at a presymptomatic stage until
      death to investigate its potential neuroprotective effects in this mouse model
      and found that survival time in the riluzole group was significantly increased in
      comparison to placebo-treated transgenic controls. Additionally, the progressive
      weight loss was delayed and significantly reduced by riluzole treatment;
      behavioral testing of motor coordination and spontaneous locomotor activity,
      however, showed no statistically significant differences. We also examined the
      formation of the HD characteristic neuronal intranuclear inclusions (NII)
      immunohistologically. At a late disease stage, striatal NII from riluzole-treated
      transgenic mice showed profound changes in ubiquitination, i.e., NII were less
      ubiquitinated and surrounded by ubiquitinated micro-aggregates. Staining with
      antibodies directed against the mutated huntingtin revealed no significant
      difference in this component of NII. Taken together, these data suggest that
      riluzole is a promising candidate for neuroprotective treatment in human HD.

PMID- 12210871
TI  - Test-retest reliability of the unified Parkinson's disease rating scale in
      patients with early Parkinson's disease: results from a multicenter clinical
      trial.
AB  - Our objective was to assess the test-retest reliability of the Unified
      Parkinson's Disease Rating Scale (UPDRS). The UPDRS is the most widely used
      instrument for measuring severity of parkinsonian symptoms in clinical research
      and in practice. The validity and inter-rater reliability of this scale have been
      previously studied. We examined the test-retest (intrarater) reliability of the
      UPDRS and derived subscales. Four hundred patients with early-stage Parkinson's
      disease (PD) who were participating in a multicenter clinical trial were
      evaluated using the UPDRS on two separate occasions (screening and baseline
      visits) prior to receiving treatment. The same neurologist at each center rated
      the subjects at both examinations that were, on average, 14.6 +/- 7.6 days apart
      (range 3-36 days). Test-retest reliability was estimated using the intraclass
      correlation coefficient (ICC) for the total UPDRS score, the mental, ADL, and
      motor subscale scores, and other derived subscale scores. Weighted kappa
      statistics were calculated for individual UPDRS items. The ICCs for the UPDRS
      scores were as follows: total score, 0.92; mental, 0.74; ADL, 0.85; motor, 0.90.
      ICCs for derived symptom-based scales ranged from 0.69-0.88. Reliability of
      specific items was generally lower than for summary scales. Reliability was
      slightly better in patients for whom the testing interval was within 14 days.
      Based on conventional standards, the UPDRS scores were found to have excellent
      test-retest reliability in this sample of patients with early PD rated by
      academic movement disorder specialists. The findings are in agreement with
      previous reports on interrater reliability.

PMID- 12210872
TI  - Further evidence for an association of the paraoxonase 1 (PON1) Met-54 allele
      with Parkinson's disease.
AB  - Paraoxonase1 (PON1) is an arylesterase mainly expressed in the liver that
      hydrolyzes organophosphates such as pesticides, reported risk factors for
      Parkinson's disease (PD), and other neurotoxins. A Leu-Met 54 polymorphism in the
      gene for PON1-affecting enzyme activity was recently shown, employing a new
      restriction enzyme technique, to be associated with Parkinson's disease. We
      examined the same polymorphism by automated capillary sequencing in a sample of
      Caucasian subjects from the Stockholm area in Sweden (127 healthy individuals and
      114 patients with PD) and found similar distributions and a similar difference in
      our sample. The genotype distribution in our PD material was LL 36.0%, LM 45.6%,
      and MM 18.4%; in our control material, it was LL 45.7%, LM 44.1%, and MM 10.2%.
      Based on the previously established increase in allele frequencies of the lower
      activity Met-variant of PON1, we could confirm a significant association using a
      one-sided chi(2) test. Results remained significant with a two-sided chi(2) test,
      allowing for both increases and decreases in frequencies. Our data confirm an
      association between the PON1 Leu-Met 54 polymorphism and PD by demonstrating a
      similar association. The distribution between familial and nonfamilial PD
      patients was equal. No other synonymous or nonsynonymous polymorphisms were found
      in the sequenced coding region of PON1.

PMID- 12210873
TI  - ACT and UCH-L1 polymorphisms in Parkinson's disease and age of onset.
AB  - alpha1-Antichymotrypsin (ACT) and ubiquitin carboxy-terminal hydrolase L1 (UCH
      L1) have been suggested as susceptibility factors for Parkinson's disease (PD).
      We replicated these findings in a Chinese case-control sample consisting of 160
      PD cases and 160 carefully matched control subjects. Genotypes were determined
      using polymerase chain reaction and BstN1 or Rsa1 restriction enzyme assay.
      Analysis showed no significant difference between PD patients and controls for
      genotype or allele frequencies of the ACT and UCH-L1 S18Y polymorphisms. UCH-L1
      S18Y polymorphism carriers, however, were found to be significantly less frequent
      in early-onset PD patients with a reduced risk of 0.557 (95% C.I. = 0.314-0.985;
      P = 0.043). These data suggest that ACT polymorphism does not influence the risk
      for developing PD. UCH-L1 S18Y polymorphism, however, may be a weak protective
      factor against early-onset PD.

PMID- 12210874
TI  - Prevalence of stroke in Parkinson's disease: a postmortem study.
AB  - The results of previous epidemiological studies of the relationship between
      Parkinson's disease and stroke have been conflicting; some showing a reduced risk
      of ischaemic and haemorrhagic stroke during life, and others indicating an
      increased likelihood of stroke-related death. We compared the frequency of
      cerebral infarcts and haemorrhages at postmortem in 100 cases of pathologically
      verified idiopathic Parkinson's disease and 100 age-matched control brains. No
      significant differences were found in the numbers of infarcts or haemorrhages or
      stroke-related deaths between the two groups. Our findings do not indicate either
      a protective effect against stroke, or a greater susceptibility to death from
      stroke, in the population studied.

PMID- 12210875
TI  - Sleep disorders in Parkinson's disease.
AB  - We sought to estimate the frequency and nature of sleep disturbances in Indian
      Parkinson's disease (PD) patients. One hundred forty nine consecutive PD patients
      attending the Movement Disorders Clinic of the All India Institute of Medical
      Sciences, New Delhi, India and 115 age-matched healthy controls participated.
      After clinical evaluation, sleep assessment was done using a 23-question,
      validated sleep questionnaire. Mean age of PD patients and the duration of
      illness were 58.37 (S.D. 10.45) years and 5.7 (S.D. 3.85) years, respectively.
      The mean age of the controls was 56.50 (S.D. 11.45) years (P > 0.05). Sleep
      problems were seen in 63 (42%) PD patients compared to 12% of controls. These
      were: insomnia in 32%, nightmares in 32%, and excessive day time sleepiness in
      15% of PD patients as compared with 5%, 5% and 6%, respectively, in controls (P <
      0.025). Presence of nightmares was significantly associated with higher Hoehn and
      Yahr score (P < 0.002), high unified Parkinson's disease rating scale (UPDRS)
      Part I score (P < 0.000) and levodopa dose (P < 0.025). Excessive daytime
      sleepiness correlated with higher Hoehn and Yahr stage (P < 0.004), and levodopa
      dose (P < 0.040). The sleep latency was longer in PD patients as compared to
      controls (P < 0.000). Multiple logistic regression analysis showed association of
      sleep disturbances with UPDRS Part III, Schwab and England score, levodopa dose,
      rigidity score, and bradykinesia score. Sleep problems are much more common in PD
      patients compared to controls (P < 0.001), and correlate with increased severity
      of disease.

PMID- 12210876
TI  - Monosymptomatic resting tremor and Parkinson's disease: a multitracer positron
      emission tomographic study.
AB  - We sought to elucidate the relationship between monosymptomatic resting tremor
      (mRT) and Parkinson's disease (PD). We studied eight mRT patients (mean Hoehn and
      Yahr [H&Y], 1.1 +/- 0.4), eight patients with PD (mean H&Y, 1.5 +/- 0.8), who
      showed all three classic parkinsonian symptoms, and seven age-matched healthy
      subjects. Subjects underwent cerebral magnetic resonance imaging (MRI) and
      multitracer positron emission tomography (PET) with 6-[(18)F]fluoro-L-dopa (F
      dopa), [(18)F]fluorodeoxyglucose (FDG), and [(11)C]raclopride (RACLO). PD and mRT
      patients did not show significant differences in F-dopa-, RACLO-, or FDG-PET
      scans. In F-dopa- and RACLO-PET, significant differences between the pooled
      patient data and control subjects were found for the following regions: anterior
      and posterior putamen ipsilateral and contralateral to the more affected body
      side, and ipsilateral and contralateral putaminal gradients of the K(i) values.
      Furthermore, we found a difference for the normalized glucose values of the whole
      cerebellum between the control group (0.94 +/- 0.06) and PD patients (1.01 +/-
      0.04; P < 0.05) but not for the mRT group (0.97 +/- 0.03). Our findings indicate
      that monosymptomatic resting tremor represents a phenotype of Parkinson's
      disease, with a nearly identical striatal dopaminergic deficit and postsynaptic
      D2-receptor upregulation in both patient groups. We suggest that the cerebellar
      metabolic hyperactivity in PD is closer related to akinesia and rigidity rather
      than to tremor.

PMID- 12210877
TI  - [18F]-Dopa positron emission tomography imaging in early-stage, non-parkin
      juvenile parkinsonism.
AB  - There are few reports of positron emission tomography (PET) in juvenile
      parkinsonism (JP). We report on the results of (18)F-6-fluoro-L-dopa (FD) PET in
      a 14-year-old patient with JP of 5 years duration associated with atypical
      features. This is the youngest subject to be investigated to date. There was a
      severe asymmetric reduction in striatal FD uptake, with a rostrocaudal gradient
      in the putamen similar to that seen in adult-onset idiopathic parkinsonism.
      Extensive DNA analysis in this patient did not show mutations in the parkin gene.

PMID- 12210878
TI  - Accuracy of acute levodopa challenge for clinical prediction of sustained long
      term levodopa response as a major criterion for idiopathic Parkinson's disease
      diagnosis.
AB  - Clinical idiopathic Parkinson's disease (PD) diagnosis requires following strict
      clinical criteria. Final definitive diagnosis can only be made after pathological
      confirmation and, despite following clinical criteria, several cases are
      misdiagnosed. We assessed sensitivity and specificity of acute challenge with
      levodopa (L-dopa) to predict sustained long-term L-dopa responsiveness as a major
      criterion for clinical diagnosis of PD. A consecutive series of 82 patients first
      seen at a movement disorders clinic with a parkinsonian syndrome without specific
      diagnosis was included. A second examiner, blind to the presumptive diagnosis,
      performed in each patient an acute challenge with 250/50 mg of L-dopa-carbidopa
      and rated the test as positive or negative according to whether values reached a
      minimal 30% of improvement on UPDRS scores. Positive tests were considered
      supportive of presumptive clinical diagnosis of Parkinson's disease. Blind to
      test results and according to clinical presumption, the first examiner started
      patient treatment with the necessary L-dopa dose or, alternatively, until
      reaching 1 g for 1 month in those who failed to display a positive test response.
      At 24 month follow-up, they were re-tested with 1 g for 1 month when required. At
      this point, clinical criteria of the U.K. Parkinson's Disease Society Brain Bank
      were applied and definitive clinical diagnosis of PD was made. Sensitivity,
      specificity, and positive predictive ratio for acute challenge were calculated.
      Overall sensitivity and specificity of acute L-dopa challenge to predict clinical
      diagnosis of PD was 70.9% and 81.4%, respectively; positive predictive ratio was
      88.6%. When patients were divided into three groups according to their UPDRS
      motor section score at initial examination, sensitivity and specificity varied:
      Group I (<or= 10), 71.4% and 100%; Group II (11-20), 75% and 75%; and Group III
      (>or=21), 36.4% and 87%, respectively. Positive predictive ratio increased to
      100% in Group I and to 87.5% in Group III. The positive result of initial acute L
      dopa challenge predicts chronic L-dopa responsiveness as major criterion of PD in
      all patients with UPDRS motor scores lower than 10.

PMID- 12210879
TI  - Acupuncture therapy for the symptoms of Parkinson's disease.
AB  - Interest in alternative medical treatments, including acupuncture, is increasing.
      Alternative treatments must be subjected to the same objective standards as all
      medical treatments. A non-blinded pilot study of the safety, tolerability, and
      efficacy of acupuncture (ACUPX) for the symptoms of (PD) was performed. Twenty PD
      patients (mean age, 68 years; disease duration, 8.5 years; Hoehn and Yahr [H&Y]
      stage, 2.2; Unified Parkinson's Disease Rating Scale score [UPDRS], 38.7) each
      received acupuncture treatments by a licensed acupuncturist. All patients were
      treated with two acupuncture treatment sessions per week. The first seven
      patients received 10 treatments and the last 13 patients 16 treatments. Patients
      were evaluated before and after ACUPX with the Sickness Impact Profile (SIP);
      UPDRS; H & Y; Schwab and England (S & E); Beck Anxiety Inventory (BAI); Beck
      Depression Inventory (BDI); quantitative motor tests, including timed evaluations
      of arm pronation supination movements, finger dexterity, finger movements between
      two fixed measured points, and the stand-walk-sit test; and a patient
      questionnaire designed for the study. Following ACUPX, there were no significant
      changes in the UPDRS, H&Y, S&E, BAI, BDI, quantitative motor tests, total SIP or
      the two SIP Dimension scores. Analysis of the 12 SIP categories not corrected for
      multiple comparisons revealed a post-ACUPX improvement in the sleep and rest
      category only (P = 0.03). On the patient questionnaire, 85% of patients reported
      subjective improvement of individual symptoms including tremor, walking,
      handwriting, slowness, pain, sleep, depression, and anxiety. There were no
      adverse effects. ACUPX therapy is safe and well tolerated in PD patients. A range
      of PD and behavioral scales failed to show improvement following ACUPX other than
      sleep benefit, although patients reported other discrete symptomatic
      improvements. A broad battery of tests in PD patients suggested that ACUPX
      resulted in improvement of sleep and rest only. This finding needs to be verified
      using more in-depth and controlled evaluation of ACUPX for PD-related sleep
      disturbance.

PMID- 12210880
TI  - Long-term follow-up of globus pallidus chronic stimulation in advanced
      Parkinson's disease.
AB  - To assess the long-term follow-up of the globus pallidus internus (GPi)
      stimulation, six patients were evaluated every year by using the Unified
      Parkinson's Disease Rating Scale (UPDRS). Three years postoperatively, GPi
      stimulation led to a significant improvement of dyskinesia severity (50%, P =
      0.05) and activities of daily living (subscore of quality of life scale, 9%, P =
      0.05). However, the improvement induced by chronic pallidal stimulation on the
      mean daily duration in the off state was lost at the last assessment.

PMID- 12210881
TI  - Contribution of the interleukin-1beta gene polymorphism in multiple system
      atrophy.
AB  - We studied genetic polymorphisms in the promoter region at position -511 of the
      interleukin (IL) -1beta gene (IL-1B-511) and at position -889 of the IL-1alpha
      gene (IL-1A-889), in 111 Japanese patients with multiple system atrophy (MSA) and
      160 controls. The distribution of IL-1B-511 was significantly different between
      MSA patients and controls, because of the under-representation of patients with
      homozygotes for allele 2 (IL-1B-511*2), a high producer of IL-1beta. The
      frequency of IL-1A-889*2, a high secretor of IL-1alpha, was also decreased in MSA
      patients. Our findings suggest that abnormal cytokine expression may be
      implicated in the pathogenesis of MSA.

PMID- 12210882
TI  - Presynaptic parkinsonism in multiple system atrophy mimicking Parkinson's
      disease: a clinicopathological case study.
AB  - We describe the clinicopathological findings in a patient aged 63 years at death
      who, at age 55 years, developed levodopa-responsive parkinsonism with no atypical
      features. A diagnosis of idiopathic Parkinson's disease (PD) was made. During the
      clinical course, fluctuations and dyskinesias appeared. Eight years after onset,
      he was successfully treated with subthalamic nucleus stimulation but died 3 weeks
      postoperatively from pulmonary embolus. Brain autopsy showed marked neuronal loss
      and gliosis in the substantia nigra and locus coeruleus, and, to a much lesser
      extent, in the basis pontis, inferior olivary nuclei, and cerebellar cortex.
      Striatum was normal. There were numerous oligodendroglial and neuronal
      cytoplasmic inclusions and neuropil threads, the highest density being localized
      in the pons and cerebellar white matter. No Lewy bodies were observed. We
      conclude that nigral, presynaptic parkinsonism may occur in multiple system
      atrophy, which even in the long run can be indistinguishable from PD. Putaminal
      preservation accounts for good response to both levodopa therapy and subthalamic
      nucleus stimulation.

PMID- 12210883
TI  - Post-streptococcal autoimmune neuropsychiatric disease presenting as paroxysmal
      dystonic choreoathetosis.
AB  - Paroxysmal dystonic choreoathetosis (PDC) is an episodic, non-kinesogenic,
      extrapyramidal movement disorder. It is postulated that PDC is an ion channel
      disorder. We describe a sporadic case of paroxysmal dystonic choreoathetosis
      occurring after streptococcal pharyngitis. The episodes were characterized by
      abrupt-onset dystonic posturing, choreoathetosis, visual hallucinations and
      behavioral disturbance. Each episode lasted between 10 minutes and 4 hours, and
      occurred up to 4 times per day. In between attacks, examination was normal. The
      episodes waxed and waned in frequency during a 6-month illness. Magnetic
      resonance imaging of the brain was normal. Post-streptococcal neuropsychiatric
      disease has a proposed autoimmune etiology, which is supported by the presence of
      serum antibasal ganglia antibodies. Western immunoblotting of this case's serum
      demonstrated antibody binding to a basal ganglia antigens of molecular weight 80
      kDa and 95 kDa. Immunohistochemistry examination demonstrated specific antibody
      binding to large striatal neurones. We propose that autoantibodies produced in
      post-streptococcal neuropsychiatric disease cause alteration in
      neurotransmission, possibly secondary to ion channel binding.

PMID- 12210884
TI  - Tourettism and dystonia after subcortical stroke.
AB  - The term "tourettism" has been used to describe Tourette syndrome (TS)-like
      symptoms secondary to some specific cause. Tics associated with attention deficit
      hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or both, are
      commonly present in TS, but this constellation of symptoms has been rarely
      attributed to stroke. We describe two boys who suffered a subcortical stroke and
      subsequently developed hemidystonia, tics, and behavioral comorbidities. Both had
      right hemispheric stroke involving the basal ganglia at 8 years of age, and in
      both the latency from the stroke to the onset of left hemidystonia was 2 weeks.
      In addition to ADHD and OCD, both exhibited cranial-cervical motor tics but no
      phonic tics. The temporal relationship between the stroke and subsequent TS-like
      symptoms, as well as the absence of phonic tics and family history of TS symptoms
      in our patients, argues in favor of a cause and effect relationship, and the
      observed association provides evidence for an anatomic substrate for TS and
      related symptoms.

PMID- 12210885
TI  - Major and minor form of hereditary hyperekplexia.
AB  - Hyperekplexia is a hereditary neurological disorder characterized by excessive
      startle responses. Within the disorder two clinical forms can be distinguished.
      The major form is characterized by continuous generalized stiffness in the first
      year of life and an exaggerated startle reflex, accompanied by temporary
      generalized stiffness and falls, whereas in the minor form only excessive startle
      and hypnic jerks have been described. Mutations in the gene encoding the alpha-1
      subunit of the glycine receptor (GLRA1) are responsible for the major form of
      hyperekplexia but no mutation was detected in patients with the minor form in the
      large Dutch pedigree originally described by Suhren and colleagues. Here we
      describe the genetic analysis of the GLRA1 gene of two English families in which
      both forms of hyperekplexia were present. Mutation analysis revealed no genetic
      defect in the GLRA1 gene in patients carrying either the minor or major forms.
      This is further evidence that the minor form of hyperekplexia is seldom due to a
      genetic defect in the GLRA1 gene.

PMID- 12210886
TI  - Association between dopamine transporter gene polymorphism and susceptibility to
      Parkinson's disease in Japan.
AB  - We studied a polymorphism in the dopamine transporter (DAT) gene in 236 Japanese
      patients with Parkinson's disease (PD) and compared the results with 220
      controls. The 1215A/G genotype of the DAT gene was significantly different
      between PD patients and controls, suggesting a possible involvement of DAT in
      genetic susceptibility to PD.

PMID- 12210887
TI  - Did Charles Dickens describe progressive supranuclear palsy in 1857?
AB  - A character from one of Charles Dickens's lesser known works is presented, whose
      attributes suggest a possible diagnosis of progressive supranuclear palsy.

PMID- 12210888
TI  - Parkinsonian syndrome induced by amlodipine: case report.
AB  - An elderly patient who developed marked symptoms of parkinsonism in response to
      amlodipine for the treatment of arterial systemic hypertension is described. She
      had a complete reversal of her motor symptoms after discontinuation of the drug.

PMID- 12210889
TI  - Micrographia secondary to lenticular lesions.
AB  - Four patients with a stroke developed micrographia. In two patients, the
      condition was pure and in the two other patients it was associated with signs of
      writer's cramp. We conclude that infarct of the left lenticular nucleus could
      either mimic pure micrographia similar to that of Parkinson's disease or
      micrographia associated with dystonia.

PMID- 12210890
TI  - Familial essential tremor is not associated with SCA-12 mutation in southern
      Italy.
AB  - We investigated 30 patients with familial essential tremor (ET) for
      spinocerebellar ataxia type 12 (SCA-12) mutations. No patient presented a CAG
      repeat larger than 19, suggesting that familial ET and SCA-12 are distinct
      diseases.

PMID- 12210891
TI  - Impact of cervical dystonia on quality of life.
AB  - We studied the effect of cervical dystonia on quality of life in a cohort of 289
      patients by using a generic health status measurement scale (SF36). Cervical
      dystonia had a significant negative impact on quality of life compared with age
      matched general population data. This negative impact was comparable to that seen
      in multiple sclerosis, Parkinson's disease, and stroke.

PMID- 12210892
TI  - Orthostatic paroxysmal dystonia.
AB  - A 52-year-old man with a history of cerebrovascular disease presented with a 3
      year history of paroxysmal hemidystonia precipitated by assuming an upright
      position after sitting or lying down. MRA showed occlusion of the contralateral
      internal carotid artery (ICA) and near-total occlusion of the ipsilateral ICA.
      Subtraction single proton emission computed tomography demonstrated decreased
      perfusion in the contralateral frontoparietal cortex during the typical dystonic
      spell. We have coined the term "orthostatic paroxysmal dystonia" for this
      phenomenon.

PMID- 12210893
TI  - Cervical dystonia in twins.

PMID- 12210894
TI  - Survival duration of Parkinson's disease patients living in Greece who carry the
      G209A alpha-synuclein mutation.

PMID- 12210895
TI  - Hemiballism during subthalamic nucleus lesioning.

PMID- 12210896
TI  - A single FKS homologue in Yarrowia lipolytica is essential for viability.
AB  - The synthesis of beta-1,3-glucan, the structural component of the yeast cell wall
      which gives shape to the cell, occurs at the plasma membrane and is the result of
      the activity of at least a two-component complex. Fks1p is the catalytic subunit
      directly responsible for the synthesis of beta-1,3-glucan, whilst the second
      subunit, Rho1p, has a GTP-dependent regulatory role. FKS1 has been characterized
      in Saccharomyces cerevisiae, where its function is at least partially redundant
      with that of FKS2/GSC2. FKS homologues have also been identified in several other
      fungal species, including Candida albicans, Schizosaccharomyces pombe,
      Aspergillus nidulans, Cryptococcus neoformans and Paracoccidiodes brasiliensis.
      In this work, we have used degenerate oligonucleotides derived from the conserved
      regions of Fks1ps to isolate the possible FKS homologue genes of the strictly
      aerobic non-conventional yeast Yarrowia lipolytica. Using this approach, we have
      isolated a single FKS homologue which we have named YlFKS1; this codes a 1961
      amino acid protein that shows a high degree of homology with other Fksps.
      Expression analysis of YlFKS1 under different conditions affecting the cell wall
      did not reveal significant differences. Finally, attempts to obtain a Y.
      lipolytica strain containing a disrupted YlFKS1 allele failed, despite having
      used two different techniques. Taken together, these results suggest that, unlike
      S. cerevisiae, YlFKS1 is the only FKS1 homologue in Y. lipolytica and is
      essential for growth.

PMID- 12210897
TI  - Characterization of the putative maltose transporters encoded by YDL247w and
      YJR160c.
AB  - The maltose permease family of Saccharomyces cerevisiae comprises five proteins,
      three of which are characterized, MAL31, MAL61 and AGT1 and two putative
      permeases, YDL247w (MPH2) and YJR160c (MPH3). The two uncharacterized permeases
      share 100% identity and have 75% identity with MAL31 and MAL61 and 55% identity
      with AGT1. Characterization of the genes YDL247w and YJR160c confirmed that they
      encode alpha-glucoside permeases capable of transporting maltose, maltotriose,
      alpha-methylglucoside and turanose. Analysis of the promoter regions identified
      regulatory elements, binding sites for the transcriptional activator, Malx3p and
      the inhibitory protein, Mig1p. Further analysis of the flanking sequences located
      blocks of identity covering five open reading frames, indicating that this region
      was involved in chromosomal block duplication. The members of the maltose
      permease family are proteins that have strongly overlapping but nevertheless
      distinct functions, which is a selective advantage for yeast, as it reflects
      successful adaptation to the variety of environmental conditions to which the
      yeast cells are exposed; such adaptability is very important in an industrial
      context.

PMID- 12210898
TI  - HXT5 expression is determined by growth rates in Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, hexose transporter (Hxt) proteins
      transport glucose across the plasma membrane. The Hxt proteins are encoded by a
      multigene family with 20 members, of which Hxt1-4p and Hxt6-7p are the major
      hexose transporters. The remaining Hxt proteins have other or unknown functions.
      In this study, expression of HXT5 under different experimental set-ups is
      determined. In glucose-grown batch cultures, HXT5 is expressed prior to glucose
      depletion. Independent of the carbon source used in batch cultures, HXT5 is
      expressed after 24 h of growth and during growth on ethanol or glycerol, which
      indicates that growth on glucose is not necessary for expression of HXT5.
      Increasing the temperature or osmolarity of the growth medium also induces
      expression of HXT5. In fed-batch cultures, expression of HXT5 is only observed at
      low glucose consumption rates, independent of the extracellular glucose
      concentration. The only common parameter in these experiments is that an increase
      of HXT5 expression is accompanied by a decrease of the growth rate of cells. To
      determine whether HXT5 expression is determined by the growth rate, cells were
      grown in a nitrogen-limited continuous culture, which enables modulation of only
      the growth rate of cells. Indeed, HXT5 is expressed only at low dilution rates.
      Therefore, our results indicate that expression of HXT5 is regulated by growth
      rates of cells, rather than by extracellular glucose concentrations, as is the
      case for the major HXTs. A possible function for Hxt5p and factors responsible
      for increased expression of HXT5 upon low growth rates is discussed.

PMID- 12210899
TI  - ARL1 and membrane traffic in Saccharomyces cerevisiae.
AB  - To examine the functions of the Arf-like protein, Arl1p, in Saccharomyces
      cerevisiae, a null allele, arl1delta::HIS3, was constructed in two strains. In
      one background only, loss of ARL1 resulted in temperature-sensitive (ts) growth
      (suppressed on high-osmolarity media). Allelic variation at the SSD1 locus
      accounted for differences between strains. Strains lacking ARL1 exhibited several
      defects in membrane traffic. First, arl1delta strains secreted less protein as
      measured by TCA-precipitable radioactivity found in the media of [(35)S]-labelled
      cells. A portion of newly synthesized carboxypeptidase Y (CPY) was secreted
      rather than correctly targeted to the vacuole. Uptake of the fluid-phase marker,
      lucifer yellow, was reduced. All these phenotypes were exacerbated in an ssd1
      background. The ts phenotype of the arl1deltassd1 strain was suppressed by YPT1,
      the yeast Rab1a homologue, suggesting that ARL1 and YPT1 have partially
      overlapping functions. These findings demonstrate that ARL1 encodes a regulator
      of membrane traffic.

PMID- 12210900
TI  - Vectors designed for efficient molecular manipulation in Candida albicans.
AB  - Functional studies on genes of Candida albicans have been hampered by the fact
      that few vectors are available for efficient cloning and expression in C.
      albicans, in contrast to Saccharomyces cerevisiae. Here we report that six
      vectors were constructed for molecular manipulation in C. albicans. All of them
      contained the autonomous replicating sequence ARS2 and the uracil gene as a
      selective marker. Introduction of multicloning site (MCS) facilitated directional
      cloning into various convenient restriction sites is discussed. Distal to the
      MCS, the additions of sequences encoding yeast-enhanced green fluorescent protein
      3 (yEGFP3) and the terminator of chitin synthase 2 (TCHS2) enabled us to express
      an open reading frame (ORF) with its own promoter as a GFP fusion protein, so
      that its intracellular localization could be easily determined. A vector of 7.4
      kb was also constructed to express a cloned ORF as a GFP fusion protein under the
      control of an inducible MET3 promoter (PMET3) located proximal to the MCS. Since
      this vector was relatively large in size for expressing ORFs, two additional
      vectors of 6.7 kb were constructed by inserting PMET3 and TCHS2 proximal and
      distal to the MCS of the above vector containing MCS only, respectively. These
      six vectors made it possible to study C. albicans in greater detail. They can be
      used in identification of a promoter, intracellular localization of a protein,
      and in the induction of lethal genes.

PMID- 12210901
TI  - Physiological role of the second alcohol oxidase gene MOD2 in the methylotrophic
      growth of Pichia methanolica.
AB  - The methylotrophic yeast Pichia methanolica has nine multiple alcohol oxidase
      (AOD) isozymes, which can be detected on native electrophoretic polyacrylamide
      gel and are encoded by two genes, MOD1 and MOD2. The aim of this work is to
      reveal the physiological roles of these AOD subunits, especially that of Mod2p,
      encoded by the second AOD-encoding gene, MOD2. A strain expressing only MOD2
      showed severe growth inhibition with a low concentration of methanol (0.1%), but
      its growth was restored with an increase in the methanol concentration (up to
      3%). The expression of MOD2 using the CbAOD1 promoter in the Candida boidinii
      alcohol oxidase-depleted strain was more advantageous for methylotrophic growth
      with high methanol concentrations than that of MOD1. The expression of MOD2 was
      not observed under derepression conditions (0% methanol), and the expression
      level increased with an increase in the methanol concentration used for
      induction. The expression of MOD1 was observed under derepression conditions and
      was rather constant throughout the tested methanol concentration range.
      Therefore, the ratio of Mod2p to Mod1p in an active AOD octamer was proved to be
      mainly controlled by changes in the MOD2 mRNA level. These and other results show
      that Mod2p is a unique AOD subunit more adapted to methylotrophic growth with
      high methanol concentrations (3%) than Mod1p.

PMID- 12210902
TI  - Genetic interactions link ARF1, YPT31/32 and TRS130.
AB  - A genetic screen for synthetic lethal interactions with arf1(-) identified a
      recessive mutation in TRS130, one of 10 components in the trafficking protein
      particle (TRAPP) complex (Sacher et al., 2000). As TRS130 is an essential gene,
      the synthetic lethal allele (trs130-101) is a novel one that requires ARF1 for
      viability. This allele was found to exhibit no defects in secretory function,
      i.e. processing of carboxypeptidase Y or invertase. YPT31 and YPT32 were
      identified in a subsequent screen as high-copy suppressors of arf1(-)trs130-101.
      Increasing the gene dosage of YPT31/32 also suppressed lethality resulting from
      deletion of TRS130 or TRS120 but not three other essential TRAPP subunit-encoding
      genes. Although unable to suppress defects in several alleles of ARF1, increasing
      the gene dosage of YPT31/32 suppressed the cold sensitivity of gcs1(-), an Arf
      GTPase-activating protein (GAP). Thus, these genetic interactions provide initial
      evidence for linkage of Arf and TRAPP signalling and for Ypt31/32 proteins
      functioning downstream of both components in the TRAPP complex and of Arf
      signalling via the Gcs1 Arf GAP.

PMID- 12210904
TI  - Novel methodology for the archiving and interactive reading of clinical magnetic
      resonance spectroscopic imaging.
AB  - Archiving clinical magnetic resonance spectroscopic imaging (MRSI) data and
      presenting the data to specialists (e.g., neuroradiologists, neurosurgeons,
      neurologists, neuro-oncologists, and MR scientists) who work in different
      physical locations is a practical problem of significance. This communication
      describes a novel solution. The study hypothesis was that it is possible to use
      widely available distributed computing techniques to create a clinical MRSI user
      interface addressable from any personal computer with a suitable network
      connection. A worldwide web MRSI archive and interface system was created that
      permits the user to interactively view individual MRSI voxel spectra with
      correlation to MR images and to parametric spectroscopic images. Web browser
      software (i.e., Netscape and Internet Explorer) permits users in various physical
      locations to access centrally archived MRSI data using a variety of operating
      systems and client workstations. The system was used for archiving and displaying
      more than 1000 clinical MRSI studies performed at the authors' institution. The
      system also permits MRSI data to be viewed via the Internet from distant
      locations worldwide. The study illustrates that widely available software
      operating within highly distributed electronic networks can be used for archiving
      and interactive reading of large amounts of clinical MRSI data.

PMID- 12210903
TI  - Characterization of Ypr1p from Saccharomyces cerevisiae as a 2
      methylbutyraldehyde reductase.
AB  - The metabolism of aldehydes and ketones in yeast is important for biosynthetic,
      catabolic and detoxication processes. Aldo-keto reductases are a family of
      enzymes that are able to reduce aldehydes and ketones. The roles of individual
      aldo-keto reductases in yeast has been difficult to determine because of
      overlapping substrate specificities of these enzymes. In this study, we have
      cloned, expressed and characterized the aldo-keto reductase Ypr1p from the yeast
      Saccharomyces cerevisiae and we describe its substrate specificity. The enzyme
      displays high specific activity towards 2-methylbutyraldehyde, as well as other
      aldehydes such as hexanal. It exhibits extremely low activity as a glycerol
      dehydrogenase. The enzyme functions over a wide pH range and uses NADPH as co
      factor. In comparison to other mammalian and yeast aldo-keto reductases, Ypr1p
      has relatively high affinity for D,L-glyceraldehyde (1.08 mM) and hexanal (0.39
      mM), but relatively low affinity for 4-nitrobenzaldehyde (1.07 mM). It displays
      higher specific activity for 2-methylbutyraldehyde than does yeast alcohol
      dehydrogenase and has a K(m) for 2-methyl butyraldehyde of 1.09 mM. The enzyme is
      expressed during growth on glucose, but its levels are rapidly induced by osmotic
      and oxidative stress. Yeast in which the YPR1 gene has been deleted possess 50%
      lower 2-methylbutyraldehyde reductase activity than the wild-type strain. This
      suggests that the enzyme may contribute to 2-methyl butyraldehyde reduction in
      vivo. It may therefore play a role in isoleucine catabolism and fusel alcohol
      formation and may influence flavour formation by strains of brewing yeast.

PMID- 12210905
TI  - Recessed elliptical-centric view-ordering for contrast-enhanced 3D MR angiography
      of the carotid arteries.
AB  - Fast arterial-venous transit in the carotid arteries requires accurate, reliable
      timing of the acquisition to the bolus transit to maximize arterial signal and
      minimize venous artifacts. The rising edge of the bolus is not utilized in
      conventional elliptical-centric view-ordering because the critical k-space center
      must be acquired with full arterial enhancement. In this study, a recessed
      elliptical-centric view-ordering scheme is introduced in which the k-space center
      is acquired a few seconds following scan initiation. The recessed view-ordering
      is shown to be more robust to timing errors than the conventional scheme in a
      study of 37 patients.

PMID- 12210906
TI  - Preliminary report on in vivo coronary MRA at 3 Tesla in humans.
AB  - Current limitations of coronary magnetic resonance angiography (MRA) include a
      suboptimal signal-to-noise ratio (SNR), which limits spatial resolution and the
      ability to visualize distal and branch vessel coronary segments. Improved SNR is
      expected at higher field strengths, which may provide improved spatial
      resolution. However, a number of potential adverse effects on image quality have
      been reported at higher field strengths. The limited availability of high-field
      systems equipped with cardiac-specific hardware and software has previously
      precluded successful in vivo human high-field coronary MRA data acquisition. In
      the present study we investigated the feasibility of human coronary MRA at 3.0 T
      in vivo. The first results obtained in nine healthy adult subjects are presented.

PMID- 12210907
TI  - In vivo monitoring of hepatic glutathione in anesthetized rats by 13C NMR.
AB  - A method for in vivo (13)C NMR monitoring of hepatic glutathione (GSH) in intact,
      anesthetized rats has been developed. Studies were conducted using a triple
      tuned, surgically implanted surface coil designed for this animal model. The coil
      permitted complete decoupling and sufficient resolution in the (13)C NMR spectrum
      to monitor the time course of hepatic (13)C-metabolites of intravenously
      administered 2-(13)C-glycine, particularly GSH at 44.2 ppm and serine signals at
      61.1 and 57.2 ppm, respectively. It further allowed concomitant monitoring of
      high-energy phosphagens and intracellular pH by (31)P NMR. To confirm in vivo NMR
      peak assignments, we compared high-resolution 2D (1)H[(13)C] heteronuclear
      multiple quantum coherence and 1D (13)C spectra of hepatic perchloric acid
      extracts to those of authentic standards. The fractional isotopic enrichment of
      hepatic (13)C-glycine increased exponentially at a rate of 1.68 h(-1) and reached
      its plateau level of 81% in 2 h. The (13)C fractional isotopic enrichment of GSH
      increased exponentially at a rate of 0.316 h(-1) and reached 55% after 4 h of 2
      (13)C-glycine infusion, but without achieving a plateau. To confirm that the
      resonance at 44.2 ppm resulted from GSH, a rat was given an intravenous dose of 2
      oxothiazolidine-4-carboxylic acid (OTC), a cysteine precursor that increases
      intracellular GSH. As expected, with OTC administration the hepatic (13)C GSH-to
      glycine peak area increased more than sevenfold.

PMID- 12210908
TI  - Quantitative 1H-magnetic resonance spectroscopy of human brain: Influence of
      composition and parameterization of the basis set in linear combination model
      fitting.
AB  - Localized short-echo-time (1)H-MR spectra of human brain contain contributions of
      many low-molecular-weight metabolites and baseline contributions of
      macromolecules. Two approaches to model such spectra are compared and the data
      acquisition sequence, optimized for reproducibility, is presented. Modeling
      relies on prior knowledge constraints and linear combination of metabolite
      spectra. Investigated was what can be gained by basis parameterization, i.e.,
      description of basis spectra as sums of parametric lineshapes. Effects of basis
      composition and addition of experimentally measured macromolecular baselines were
      investigated also. Both fitting methods yielded quantitatively similar values,
      model deviations, error estimates, and reproducibility in the evaluation of 64
      spectra of human gray and white matter from 40 subjects. Major advantages of
      parameterized basis functions are the possibilities to evaluate fitting
      parameters separately, to treat subgroup spectra as independent moieties, and to
      incorporate deviations from straightforward metabolite models. It was found that
      most of the 22 basis metabolites used may provide meaningful data when comparing
      patient cohorts. In individual spectra, sums of closely related metabolites are
      often more meaningful. Inclusion of a macromolecular basis component leads to
      relatively small, but significantly different tissue content for most
      metabolites. It provides a means to quantitate baseline contributions that may
      contain crucial clinical information.

PMID- 12210909
TI  - Orientational diffusion reflects fiber structure within a voxel.
AB  - Several new MR techniques have been introduced to infer direction through
      diffusion in multiple nerve fiber bundles within a voxel. To date, however, there
      has been no physical model reported to evaluate these methodologies and their
      ability to determine fiber orientation. In this article a model of diffusion
      analogous to nerve fibers is presented. Diffusion measurements at multiple
      closely spaced angles of 15 degrees in samples with different fiber orientations
      are compared with theoretical calculations for restricted diffusion in
      cylindrical geometry. Orientational diffusion measurements are shown to reflect
      fiber geometry and theoretical predictions to within 10%. Simulations of fiber
      crossings within a voxel suggest fiber orientation does not correspond to the
      direction of the largest measured diffusion coefficient, but theoretical
      knowledge of signal decay curves can predict the shape of these diffusion
      coefficient contours for given fiber orientation probabilities.

PMID- 12210910
TI  - Orientational dependence of T2 relaxation in articular cartilage: A microscopic
      MRI (microMRI) study.
AB  - The experiments reported herein are the first MRI investigations of the
      orientational dependence of T(2) relaxation in articular cartilage at microscopic
      resolution over the 360 degrees angular space. For each of six canine cartilage
      specimens, 48 independent T(2)-weighted proton images were acquired for 12
      different specimen orientations. Pixel-wise monoexponential fits of these proton
      images produced 12 T(2) relaxation images, each with an in-plane pixel resolution
      of 13.7 microm. Cartilage T(2) as a function of specimen orientation was shown to
      follow approximately the angular dependence of the nuclear dipole-dipole
      interaction, with local maxima at approximately 55 degrees, 125 degrees, 235
      degrees, and 305 degrees. However, the relative amplitudes of the T(2) maxima
      deviated somewhat from those expected from the dipolar interaction. The
      amplitudes of these maxima also varied with tissue depth: the largest amplitudes
      were found in the radial zone, intermediate amplitudes were found in the
      superficial zone, and there was a continuous decrease in amplitude approaching
      the transitional zone from the superficial zone above and the radial zone below.
      We explain the discrepancy between the observed T(2) anisotropy and the angular
      dependence of the dipolar interaction by means of a simple model which considers
      the average of one isotropic and two anisotropic spin populations-the first being
      associated with "free" water, and the latter two arising from collagen-associated
      waters. We show that even for the "long" T(2) components, which arise in multiple
      compartment studies of collagen-water systems, there appears to be two
      subpopulations. Each has the same peak value of T(2), but the angular dependence
      of one is shifted in phase by 90 degrees relative to the other by virtue of the
      fact that each is associated with groups of mutually perpendicular fibrils.

PMID- 12210911
TI  - Effects of intracellular pH, blood, and tissue oxygen tension on T1rho relaxation
      in rat brain.
AB  - The effects of intracellular pH (pH(i)), paramagnetic macroscopic, and
      microscopic susceptibility on T(1) in the rotating frame (T(1rho)) were studied
      in rat brain. Intracellular acidosis was induced by hypercapnia and pH(i),
      T(1rho), T(2), diffusion, and cerebral blood volume (CBV) were quantified. Taking
      into account the CBV contribution, a prolongation of parenchymal T(1rho) by 4.5%
      was ascribed to a change in tissue water relaxation caused by a one unit drop in
      pH(i). Blood T(1rho) was found to prolong linearly with blood oxygenation
      saturation (Y). The macroscopic susceptibility contribution to parenchymal
      T(1rho) was assessed both through BOLD and an iron oxide contrast agent, AMI-227.
      The T(1rho) data from these experiments could be described by intravascular
      effects with insignificant effects of susceptibility gradients on tissue water.
      Tissue oxygen tension (PtO(2)) was manipulated and monitored with microelectrodes
      to assess its plausible contribution to microscopic susceptibility and
      relaxation. Parenchymal T(1rho) was virtually unaffected by variations in the
      PtO(2), but T(1) was shortened in hyperoxia and T(2) showed a negative BOLD
      effect in hypoxia. It is demonstrated that pH(i) directly modulates tissue
      T(1rho), possibly through its effect on proton exchange; however, neither BOLD
      nor PtO(2) directly influence tissue T(1rho). The observations are discussed in
      the light of physicochemical mechanisms contributing to the ischemic T(1rho)
      changes.

PMID- 12210912
TI  - Cerebral spinal fluid contamination of the measurement of the apparent diffusion
      coefficient of water in acute stroke.
AB  - The measurement of the apparent diffusion coefficient (ADC) of water in brains of
      stroke patients is used in models developed to help distinguish reversible from
      irreversible ischemic injury. The ADC by conventional methods may be
      overestimated by the presence of cerebral spinal fluid (CSF) in sulci and
      perivascular spaces. In this study the hypothesis that DWI with CSF suppression
      (FLAIR-DWI) would result in different ADC values than those obtained with the
      conventional DWI technique was investigated. Thirty-one patients with stroke
      onset of less than 6 hr and an acute lesion on conventional DWI were studied.
      Both conventional isotropic DWI and FLAIR-DWI were performed using a single-shot
      echo-planar technique. In all 31 patients, CSF-suppressed ADC was lower than
      conventional ADC. The mean (SD) of the 31 patients' lesion ADC was 0.64 (0.08) x
      10(-3) mm(2) s(-1) with FLAIR-DWI and 0.72 (0.09) x 10(-3) mm(2) s(-1) with
      conventional DWI (P < 0.001). The overestimation of ADC in conventional DWI
      corresponded to the percentage of the voxel that contained CSF. Suppression of
      CSF leads to lesion ADC values that are more homogeneous and more than 15% lower
      than those obtained with conventional DWI techniques. This suggests that FLAIR
      DWI ADC measurements are more accurate than conventional ADC maps.

PMID- 12210913
TI  - MRI of lungs using partial liquid ventilation with water-in-perfluorocarbon
      emulsions.
AB  - A novel (1)H-MRI contrast modality for rat lungs has been developed using water
      in-perfluorocarbon (PFC) emulsions for partial liquid ventilation (PLV). The
      feasibility of the new ventilation protocol for (1)H-MRI studies of lungs has
      been demonstrated. (1)H-MR images of lungs have been obtained with sensitivity
      and spatial resolution higher than those of the (19)F-MRI of lungs previously
      reported. Diffusion-weighted MRI measurements of lungs showed that the results
      obtained are related to the pulmonary architecture and functional properties of
      lungs. Although the methodology needs further improvement and evaluation, it
      appears to have great potential in a wide range of new applications in the field
      of lung MRI, such as in vivo detection of lung cancer, emphysema, and allograft
      rejection following lung transplantation. The ability of this technique to
      achieve high-quality MR images of lungs, together with its technical simplicity,
      stability, and low cost, makes this method a promising imaging technique for the
      lungs.

PMID- 12210914
TI  - Using UNFOLD to remove artifacts in parallel imaging and in partial-Fourier
      imaging.
AB  - In dynamic MRI, it is often difficult to achieve the acquisition speed required
      to resolve or freeze the temporal variations of the imaged object. Several MRI
      methods aim at speeding up the image acquisition process. Through assumptions
      and/or prior knowledge, these dynamic MRI methods allow part of the needed data
      to be calculated instead of acquired. For example, partial-Fourier imaging
      assumes that phase varies smoothly within the object, and parallel imaging (e.g.,
      simultaneous acquisition of spatial harmonics (SMASH) and sensitivity encoding
      (SENSE)) uses prior knowledge about receiver-coil sensitivity. While these
      methods accelerate acquisition, they can introduce artifacts or amplify noise in
      doing so. The present work aims at accelerating image acquisition significantly,
      while introducing almost no artifacts or noise amplification. It is shown here
      that new, extra information is gained if dynamic MRI methods are modified so that
      the sampling function changes in specific ways from time-frame to time-frame. In
      other words, the set of k-space locations that are acquired (instead of
      calculated) changes with time. The present temporal strategy, based on the
      UNaliasing by Fourier-encoding the Overlaps in the temporaL Dimension (UNFOLD)
      method, can be incorporated into common dynamic MRI methods. Results with partial
      Fourier, SMASH, and SENSE imaging are presented here, where UNFOLD's contribution
      is to very significantly reduce the artifact and/or amplified noise content. Used
      in this way, UNFOLD contributes indirectly, rather than directly to the
      improvement in image acquisition speed, as it allows companion methods to operate
      properly at greater acceleration settings than would otherwise be feasible.

PMID- 12210915
TI  - Frequency-modulated steady-state free precession imaging.
AB  - Exploration of the possibilities of steady-state free precession (SSFP)
      excitation has led to the discovery that it is tolerant of slow variations in
      spectral offset frequency. The effect has been used to eliminate banding
      artifacts from images obtained with the fully balanced SSFP imaging sequence.

PMID- 12210916
TI  - Correction of concomitant magnetic field-induced image artifacts in nonaxial echo
      planar imaging.
AB  - Echo-planar images acquired in nonaxial planes are often distorted. Such image
      distortion has limited the applications of the echo-planar imaging (EPI)
      technique. In this article, it is demonstrated that a considerable amount of the
      distortion is caused by the higher-order magnetic field concomitant with the
      linear magnetic field gradient, or the concomitant magnetic field. The image
      distortion caused by the concomitant magnetic field is more prominent when a
      higher gradient amplitude is used for readout. It is also shown that the
      concomitant magnetic field can cause ghosting and blurring. A theoretical
      analysis is performed for the concomitant field effect in nonaxial EPI images. A
      point-by-point (or line-by-line) phase correction algorithm is developed to
      correct the image distortion, ghosting, and blurring. A postreconstruction
      processing algorithm is also developed to correct image distortion with much
      higher computational efficiency. Experimental results show that both correction
      methods effectively reduce the image distortion in coronal or sagittal images.

PMID- 12210918
TI  - Fluorine electron double resonance imaging for 19F MRI in low magnetic fields.
AB  - This work demonstrates the feasibility of generating fluorine NMR images at a
      very low magnetic field of 0.015 T by making use of the Overhauser enhancement of
      (19)F NMR signal brought about by a stable, water-soluble, narrow-line
      paramagnetic contrast agent. The enhancement in the (19)F NMR images depends on
      the concentration of the single electron contrast agent, the pO(2), and the
      electron paramagnetic resonance (EPR) irradiation power. The applicability of
      this technique for (19)F NMR imaging is demonstrated with phantom samples, where
      a time resolution of 4-10 min is achieved. Proton electron double resonance
      imaging (PEDRI) and fluorine electron double resonance imaging (FEDRI) images
      were also obtained from rat kidneys ex vivo, perfused with 10 mM Oxo63 and 10 M
      trifluoroacetic acid. The spatial and temporal resolutions of these images are
      comparable to those obtained at magnetic fields 2-3 orders of magnitude larger.
      Constant NMR frequency (628 kHz) operation permits both FEDRI and PEDRI of
      identical slices without removing the object under investigation. This
      feasibility of coregistration of proton-based anatomical PEDRI image with
      physiological FEDRI image offers good potential for studying fluorine-containing
      tracers.

PMID- 12210917
TI  - Time-resolved, undersampled projection reconstruction imaging for high-resolution
      CE-MRA of the distal runoff vessels.
AB  - Imaging of the blood vessels below the knee using contrast-enhanced (CE) MRI is
      challenging due to the need to coordinate image acquisition and arrival of the
      contrast in the targeted vessels. Time-resolved acquisitions have been successful
      in consistently capturing images of the arterial phase of the bolus of contrast
      agent in the distal extremities. Although time-resolved exams are robust in this
      respect, higher spatial resolution for the depiction of tight stenoses and the
      small vessels in the lower leg is desirable. A modification to a high-spatial
      resolution T(1)-weighted pulse sequence (projection reconstruction-time resolved
      imaging of contrast kinetics (PR-TRICKS)) that improves the through-plane spatial
      resolution by a factor of 2 and maintains a high frame rate is presented. The
      undersampled PR-TRICKS pulse sequence has been modified to double the spatial
      resolution in the slice direction by acquiring high-spatial-frequency slice data
      only after first pass of the bolus of contrast agent. The acquisition reported in
      the present work (PR-hyperTRICKS) has been used to image healthy volunteers and
      patients with known vascular disease. The temporal resolution was found to be
      beneficial in capturing arterial phase images in the presence of asymmetric
      filling of vessels.

PMID- 12210919
TI  - Proton electron double resonance imaging of the in vivo distribution and
      clearance of a triaryl methyl radical in mice.
AB  - Proton electron double resonance imaging (PEDRI) measures the spatial
      distribution of paramagnetic species in biological samples using the Overhauser
      effect. Triaryl methyl (TAM) free radicals have been developed as a spin probe
      for PEDRI since they have very long T(1e). Therefore, low RF power levels are
      sufficient to saturate the electron spin system with resultant high NMR
      enhancement facilitating application of PEDRI in living animals. In this report,
      PEDRI studies were performed at 0.02 T. The power-dependent image enhancement was
      studied using phantoms of TAM in saline, then the distribution and
      pharmacokinetics of TAM in living mice were measured. Following intravenous
      administration of 0.7 mmol/kg of TAM, enhancements of up to -34 were observed
      enabling visualization of its distribution within the body. Maximum uptake of TAM
      in the vascular compartment was seen 1 min postadministration with half-clearance
      within 5 min. Maximum uptake in the kidneys occurred at 10 min with half
      clearance at 26 min and maximum accumulation in the bladder after 50 min. Thus,
      TAM is initially compartmentalized in the vasculature and this is followed by
      rapid uptake and excretion by the kidneys. PEDRI enabled rapid imaging of the
      distribution and clearance of this paramagnetic probe and this information should
      facilitate the use of TAM as a label for oximetry and other applications. Magn
      Reson Med 48:530-534, 2002.

PMID- 12210920
TI  - Quantitation of absolute 2H enrichment of plasma glucose by 2H NMR analysis of
      its monoacetone derivative.
AB  - A simple (2)H NMR method for quantifying absolute (2)H-enrichments in all seven
      aliphatic positions of glucose following its derivatization to monoacetone
      glucose is presented. The method is based on the addition of a small quantity of
      (2)H-enriched formate to the NMR sample. When the method was applied to [2
      (2)H]monoacetone glucose samples prepared from [2-(2)H]glucose standards of known
      enrichments in the range of 0.2-2.5%, enrichment estimates derived by the NMR
      method were in good agreement with the real enrichment values of the [2
      (2)H]glucose precursors. The measurement was also applied to monoacetone glucose
      derived from human plasma glucose samples following administration of (2)H(2)O
      and attainment of isotopic steady state, where glucose H2 and body water
      enrichment are equivalent. In these studies, the absolute H2 enrichment of plasma
      glucose estimated by the formate method was in good agreement with the (2)H
      enrichment of body water measured by an independent method.

PMID- 12210921
TI  - Pathway selection by pulsed field gradients.
AB  - A method for pathway selection in a multiple spin-echo pulse sequence applying
      crusher gradients before and after each pi pulse, to dephase unwanted pathways,
      is described. This method selects the only pathway that would contribute to the
      measurable signal if the pi pulses were perfect (1,-1,1,-1, em leader ). Good
      pathway selection is essential in pulse programming, especially when the CPMG
      condition is not met. An interactive applet was also developed to deal with these
      calculations.

PMID- 12210922
TI  - Continuous arterial spin labeling using a local magnetic field gradient coil.
AB  - Continuous arterial spin labeling (ASL) using a locally induced magnetic field
      gradient for adiabatic inversion of spins in the common carotid artery of human
      volunteers is demonstrated. The experimental setup consisted of a helmet
      resonator for imaging, a circular RF surface coil for labeling, and gradient
      loops to produce a magnetic field gradient. A spin-echo (SE) echo-planar imaging
      (EPI) sequence was used for imaging. The approach is independent of the gradients
      of the MR scanner. This technology may be used if the imaging gradient system
      does not produce an appropriate magnetic field gradient at the location of the
      carotid artery-for example, in a head-only scanner-and is a prerequisite for the
      development of a system that allows continuous labeling during the imaging
      experiment.

PMID- 12210923
TI  - Volume of rat lungs measured throughout the respiratory cycle using 19F NMR of
      the inert gas SF6.
AB  - The lung volumes of mechanically ventilated rats were measured over the course of
      the respiratory cycle using the NMR signal strength from inhaled
      sulfurhexafluoride. Rats with elastase-induced emphysema showed larger lung
      volumes and slower exhalation than control rats. For humans the technique should
      be able to provide lung volume measurements at least 20 times a second.

PMID- 12210924
TI  - k-space interpretation of the Rose Model: noise limitation on the detectable
      resolution in MRI.
AB  - Noise limitation on the detected spatial resolution, described by the Rose Model,
      is well known in X-ray imaging and routinely used in designing X-ray imaging
      protocols. The purpose of this article is to revisit the Rose Model in the
      context of MRI where image data are acquired in the spatial frequency domain. A k
      space signal-to-noise ratio (kSNR) is introduced to measure the relative signal
      and noise powers in a circular annulus in k-space. It is found that the kSNR
      diminishes rapidly with k-space radius. The Rose criterion that the voxel SNR
      approximately 4 is translated to kSNR cutoff values was tested using theoretical
      derivation and experimental histogram analysis. Experiments demonstrate that data
      acquisition beyond this cutoff k-space radius adds little or no information to
      the image. In order to reduce the noise limit on spatial resolution, the signal
      strength must be improved through means such as increasing the coil sensitivity,
      contrast enhancement, and signal averaging. This finding implies that the optimal
      k-space volume to be sampled or the optimal scan time in MRI should be matched to
      the relative SNR level.

PMID- 12210925
TI  - Rapid method for correction of CSF partial volume in quantitative proton MR
      spectroscopic imaging.
AB  - Partial volume effects with cerebrospinal fluid (CSF), if uncorrected, can lead
      to underestimation of metabolite concentrations in quantitative proton magnetic
      resonance spectroscopic imaging (MRSI) of the brain. A rapid method for the
      correction of CSF partial volume effects is described based on selective CSF
      imaging using long echo time (TE) fast spin echo (FSE) magnetic resonance imaging
      (MRI). In order to achieve maximum suppression of signal from brain parenchyma,
      the FSE sequence is coupled with an inversion recovery (IR) pulse. Scan time is
      minimized using single shot (SS) IR-FSE. The method is validated against a
      current "gold standard" for the determination of CSF volumes, namely, segmented
      3D spoiled gradient-echo (SPGR) scans. Excellent agreement in CSF percentage
      determined by the two methods was found (linear regression analysis: slope = 0.99
      +/- 0.02, intercept = 2.08 +/- 0.45; mean +/- standard errors, R = 0.93) in
      pooled data from four healthy subjects. An example of the use of SS-IR-FSE for
      partial volume correction in a leukodystrophy patient with T(2) hyperintense
      lesions is demonstrated. SS-IR-FSE is a simple and rapid method for applying
      partial volume corrections in quantitative proton MRSI, which may be of
      particular value in the clinical environment when time constraints do not allow
      longer, perhaps more accurate segmentation methods to be used.

PMID- 12210926
TI  - UNFOLD using a temporal subtraction and spectral energy comparison technique.
AB  - In dynamic MRI, several methods have been demonstrated to increase acquisition
      speed by decreasing the number of sequential phase encodings. The UNFOLD
      technique interleaves the measurements of k-space, reconstructs aliased images
      from each k-space interleaf, and applies a temporal low-pass filter to obtain the
      nonaliased images. However, low-pass filter resolution of the nonaliased images
      fails if there is overlap between the spatially aliased temporal spectra. In this
      study a subtraction method was used to remove the static portion of the image.
      The aliased and nonaliased dynamic portions are then resolved by comparing the
      temporal energy of bands in the power spectrum. This method was combined with the
      3D 2 x 2 UNFOLD (a factor of 2 interleaves in two directions) technique. The
      combination resulted in a factor of 4 improvement in acquisition speed.
      Application of this method to a time-resolved, contrast-enhanced flow phantom
      study is presented.

PMID- 12210927
TI  - Simultaneous diffusion MRI measurements from multiple perfused rat hippocampal
      slices.
AB  - Rat brain slices provide a controllable tissue model in which to investigate the
      biophysical basis of diffusion-weighted magnetic resonance (MR) signal changes
      observed clinically in nervous tissue after ischemic injury. This study describes
      a new multislice perfusion chamber that allows for the simultaneous acquisition
      of diffusion-weighted MR images from multiple perfused rat hippocampal slices
      (eight slices in the present study). These images had a signal-to-noise ratio
      (SNR) of 48 +/- 3 at b = 8080 s/mm(2), which was sufficient to analyze the
      multicomponent diffusion properties of water in rat hippocampal slices. The
      tissue water diffusion parameters (f(fast) = 0.527 +/- 0.041, D(fast) = 1.268 +/-
      0.087 x 10(-3) mm(2)/s, and D(slow) = 0.060 +/- 0.003 x 10(-3) mm(2)/s) were
      stable for at least 8 hr after slice procurement (ANOVA, P > 0.05), suggesting
      that it may be possible to study the acute temporal evolution of diffusion
      changes in multiple brain slices following experimental perturbation.

PMID- 12210928
TI  - Mapping at glomerular resolution: fMRI of rat olfactory bulb.
AB  - The rat olfactory bulb contains approximately 2000 functional units called
      glomeruli which are used to recognize specific characteristics of odorants.
      Activity localization of individual glomerulae ( approximately 0.002 microL) has
      important consequences for understanding mechanisms in olfactory information
      encoding. High-resolution functional MRI (fMRI) data from the rat olfactory bulb
      are presented using the blood oxygenation level dependent (BOLD) method at 7 T.
      Either individual or clusters of fMRI voxels suggestive of activity in the
      olfactory nerve and glomerular layers were reproducibly detected with repeated 2
      min exposures of iso-amyl acetate at spatial resolution of 0.001-0.003 microL.
      The importance of glomerular clustering for olfaction and the implications of
      BOLD mapping with even higher spatial resolution (i.e., <<0.001 microL voxels)
      are discussed. High-resolution in vivo mapping of the rat olfactory bulb with
      fMRI at high magnetic field promises to provide novel data for understanding
      olfaction.

PMID- 12210929
TI  - Eliminating spurious lipid sidebands in 1H MRS of breast lesions.
AB  - Detecting metabolites in breast lesions by in vivo (1)H MR spectroscopy can be
      difficult due to the abundance of mobile lipids in the breast which can produce
      spurious sidebands that interfere with the metabolite signals. Two-dimensional J
      resolved spectroscopy has been demonstrated in the brain as a means to eliminate
      these artifacts from a large water signal; coherent sidebands are resolved at
      their natural frequencies, leaving the noncoupled metabolite resonances in the
      zero-frequency trace of the 2D spectrum. This work demonstrates that using the
      zero-frequency trace-or equivalently the average of spectra acquired with
      different echo times-can be used to separate noncoupled metabolite signals from
      the lipid-induced sidebands. This technique is demonstrated with simulations,
      phantom studies, and in several breast lesions. Compared to the conventional
      approach using a single echo time, echo time averaging provides increased
      sensitivity for the study of small and irregularly shaped lesions.

PMID- 12210930
TI  - Quantitative measurement of regional lung ventilation using 3He MRI.
AB  - A new strategy for a quantitative measurement of regional pulmonary ventilation
      using hyperpolarized helium-3 (3He) MRI has been developed. The method employs
      the build-up of the signal intensity after a variable number of (3)He breaths. A
      mathematical model of the signal dynamics is presented, from which the local
      ventilation, defined as the fraction of gas exchanged per breath within a given
      volume, is calculated. The model was used to create ventilation maps of coronal
      slices of guinea pig lungs. Ventilation values very close to 1 were found in the
      trachea and the major airways. In the lung parenchyma, regions adjacent to the
      hilum showed values of 0.6-0.8, whereas 0.2-0.4 was measured in peripheral
      regions. Monte Carlo simulations were used to investigate the accuracy of the
      method and its limitations. The simulations revealed that, at presently
      attainable signal-to-noise ratios, the ventilation parameter can be determined
      with a relative uncertainty of <5% over a wide range of values.

PMID- 12210931
TI  - In vivo GABA+ measurement at 1.5T using a PRESS-localized double quantum filter.
AB  - A point-resolved spectroscopy (PRESS)-localized double quantum filter was
      implemented on a 1.5T clinical scanner for the estimation of gamma-amino butyric
      acid (GABA) concentrations in vivo. Several calibrations were found to be
      necessary for consistent results to be obtained. The apparent filter yield was
      approximately 38%; filter strength was sufficient to reduce the singlet
      metabolite peaks in vivo to below the level of the noise. Metabolite-nulled
      experiments were performed, which confirmed that significant overlap occurred
      between macromolecule signals and the GABA resonance at 3.1 ppm. Although the
      multiplet arm at 2.9 ppm was confirmed to be relatively free of contamination
      with macromolecules, some contribution from these and from peptides is likely to
      remain; therefore, the term GABA+ is used. GABA+ concentrations were estimated
      relative to creatine (Cr) at the same echo time (TE) in a group of controls,
      studied on two occasions. The GABA+ concentration in 35-ml regions of interest
      (ROIs) in the occipital lobe was found to be 1.4 +/- 0.2 mM, with scan-rescan
      repeatability of 38%.

PMID- 12210932
TI  - Comparison of quantitative perfusion imaging using arterial spin labeling at 1.5
      and 4.0 Tesla.
AB  - High-field arterial spin labeling (ASL) perfusion MRI is appealing because it
      provides not only increased signal-to-noise ratio (SNR), but also advantages in
      terms of labeling due to the increased relaxation time T(1) of labeled blood. In
      the present study, we provide a theoretical framework for the dependence of the
      ASL signal on the static field strength, followed by experimental validation in
      which a multislice pulsed ASL (PASL) technique was carried out at 4T and compared
      with PASL and continuous ASL (CASL) techniques at 1.5T, both in the resting state
      and during motor activation. The resting-state data showed an SNR ratio of
      2.3:1.4:1 in the gray matter and a contrast-to-noise ratio (CNR) of 2.7:1.1:1
      between the gray and white matter for the difference perfusion images acquired
      using 4T PASL, 1.5T CASL, and 1.5T PASL, respectively. However, the functional
      data acquired using 4T PASL did not show significantly improved sensitivity to
      motor cortex activation compared with the 1.5T functional data, with reduced
      fractional perfusion signal change and increased intersubject variability.
      Possible reasons for these experimental results, including susceptibility effects
      and physiological noise, are discussed.

PMID- 12210933
TI  - Gastrointestinal transit times in mice and humans measured with 27Al and 19F
      nuclear magnetic resonance.
AB  - Gastric emptying and gastrointestinal (GI) transit times in mice and humans were
      monitored noninvasively by using 27Al and 19F nuclear magnetic resonance (NMR).
      Al(3+) bound to ion-exchange resin and perfluorononane were administered orally
      as selective and specific markers for the stomach and the entire GI tract,
      respectively. 27Al- and 19F-MR spectroscopy (MRS) was employed to follow
      quantitatively boli of the mixed markers in awake, fed mice over a period of 48
      hr. The selectivity of the markers was confirmed by whole-body 1H-, 27Al-, and
      19F-MRI of anesthetized mice. Gastric emptying in humans was also monitored with
      27Al-MRS of aluminum-loaded ion exchange resin. GI transit was assessed by 19F
      projection imaging of pharmaceutical capsules tagged with perfluorononane.
      Quantitative analysis of the MR data revealed that gastric emptying in humans
      proceeded linearly, whereas in mice an exponential decay was observed. This
      difference is explained by the respective feeding patterns of humans and mice.
      Humans usually achieve nearly complete gastric emptying before each meal. In
      contrast, very short delays between successive food intakes in small animals
      result in successive dilution of the stomach contents. For stomach emptying in
      mice the exponential decay constant was 74 min, whereas the half-time of the
      linear gastric emptying in humans was 30 min.

PMID- 12210934
TI  - Changes in CBF-BOLD coupling detected by MRI during and after repeated transient
      hypercapnia in rat.
AB  - The effect of hypercapnia on the cerebral metabolic rate of oxygen consumption
      (CMRO(2)) remains incompletely understood. This study examined the relationship
      between susceptibility (blood oxygenation level dependent (BOLD)) and perfusion
      weighted (flow-sensitive alternating inversion recovery (FAIR)) MRI techniques
      both during induction of repeated transient hypercapnia (THC) and after return to
      normocapnia during whisker barrel functional activation. During induction of THC
      the FAIR signal became significantly elevated over control after 100 s of
      hypercapnia (P = 0.039), with a trend of increasing significance to 5 min (P =
      0.000008). The FAIR signal in the activated cortex during subsequent normocapnia
      was significantly increased compared to pre-THC control after each successive
      period of THC. The mean grouped FAIR signal increased by 81% +/- 63% after one
      exposure (P = 0.021), by 163% +/- 55% after the second exposure (P = 0.0002), and
      by 240% +/- 54% after the third exposure (P = 0.000002). The mean grouped BOLD
      signal trended upward, but did not increase significantly during or after
      exposure 1, 2, or 3. These data demonstrate increased uncoupling of perfusion
      weighted from susceptibility imaging techniques, both in nonactivated cortex
      during hypercapnia, and with activation after multiple exposures to THC. These
      results are consistent with saturation of BOLD contrast as well as with increases
      in CMRO(2) with stimulation after multiple exposures to THC.

PMID- 12210935
TI  - Oxygen-enhanced MRI of the brain.
AB  - Blood oxygenation level-dependent (BOLD) contrast MRI is a potential method for a
      physiological characterization of tissue beyond mere morphological
      representation. The purpose of this study was to develop evaluation techniques
      for such examinations using a hyperoxia challenge. Administration of pure oxygen
      was applied to test these techniques, as pure oxygen can be expected to induce
      relatively small signal intensity (SI) changes compared to CO(2)-containing gases
      and thus requires very sensitive evaluation methods. Fourteen volunteers were
      investigated by alternating between breathing 100% O(2) and normal air, using two
      different paradigms of administration. Changes ranged from >30% in large veins to
      1.71% +/- 0.14% in basal ganglia and 0.82% +/- 0.08% in white matter. To account
      for a slow physiological response function, a reference for correlation analysis
      was derived from the venous reaction. An objective method is presented that
      allows the adaptation of the significance threshold to the complexity of the
      paradigm used. Reference signal characteristics in representative brain tissue
      regions were established. As the presented evaluation scheme proved its
      applicability to small SI changes induced by pure oxygen, it can readily be used
      for similar experiments with other gases.

PMID- 12210936
TI  - Simultaneous perfusion and BOLD imaging using reverse spiral scanning at 3T:
      characterization of functional contrast and susceptibility artifacts.
AB  - Reverse spiral scanning with arterial spin-labeling was developed at 3T to
      simultaneously detect perfusion and BOLD signals in the brain by subtracting or
      adding the control and labeled images, respectively, in the same dataset. BOLD
      contrast was improved with the longer effective echo time achieved in the reverse
      spiral scan compared to conventional forward spiral scans. Susceptibility
      artifacts near air-tissue interfaces in the brain were substantially reduced in
      the reverse spiral images due to their early data acquisition time and, hence,
      less signal attenuation. Brain activation experiments with the reverse spiral
      scan were performed on normal subjects and were compared to forward spiral
      imaging in the same subjects. The experiments demonstrated that reverse spiral
      imaging was able to detect perfusion and BOLD signals simultaneously and
      reliably, even in the brain regions with severe susceptibility-induced local
      gradients, while forward spiral scans were either not optimal for detecting the
      two functional signals at the same time or were vulnerable to susceptibility
      artifacts.

PMID- 12210937
TI  - Three-dimensional spiral MR imaging: Application to renal multiphase contrast
      enhanced angiography.
AB  - A fast MR pulse sequence with spiral in-plane readout and conventional 3D
      partition encoding was developed for multiphase contrast-enhanced magnetic
      resonance angiography (CE-MRA) of the renal vasculature. Compared to a standard
      multiphase 3D CE-MRA with FLASH readout, an isotropic in-plane spatial resolution
      of 1.4 x 1.4 mm(2) over 2.0 x 1.4 mm(2) could be achieved with a temporal
      resolution of 6 sec. The theoretical gain of spatial resolution by using the
      spiral pulse sequence and the performance in the presence of turbulent flow was
      evaluated in phantom measurements. Multiphase 3D CE-MRA of the renal arteries was
      performed in five healthy volunteers using both techniques. A deblurring
      technique was used to correct the spiral raw data. Thereby, the off-resonance
      frequencies were determined by minimizing the imaginary part of the data in image
      space. The chosen correction algorithm was able to reduce image blurring
      substantially in all MRA phases. The image quality of the spiral CE-MRA pulse
      sequence was comparable to that of the FLASH CE-MRA with increased spatial
      resolution and a 25% reduced contrast-to-noise ratio. Additionally, artifacts
      specific to spiral MRI could be observed which had no impact on the assessment of
      the renal arteries.

PMID- 12210939
TI  - Reconstruction of MR images from data acquired on an arbitrary k-space trajectory
      using the same-image weight.
AB  - A sampling density compensation function denoted "same-image (SI) weight" is
      proposed to reconstruct MR images from the data acquired on an arbitrary k-space
      trajectory. An equation for the SI weight is established on the SI criterion and
      an iterative scheme is developed to find the weight. The SI weight is then used
      to reconstruct images from the data calculated on a random trajectory in a
      numerical phantom case and from the data acquired on interleaved spirals in an in
      vivo experiment, respectively. In addition, Pipe and Menon's weight (MRM
      1999;41:179-186) is also used in the reconstructions to make a comparison. The
      images obtained with the SI weight were found to be slightly more accurate than
      those obtained with Pipe's weight.

PMID- 12210938
TI  - Time-resolved contrast-enhanced imaging with isotropic resolution and broad
      coverage using an undersampled 3D projection trajectory.
AB  - Time-resolved contrast-enhanced 3D MR angiography (MRA) methods have gained in
      popularity but are still limited by the tradeoff between spatial and temporal
      resolution. A method is presented that greatly reduces this tradeoff by employing
      undersampled 3D projection reconstruction trajectories. The variable density k
      space sampling intrinsic to this sequence is combined with temporal k-space
      interpolation to provide time frames as short as 4 s. This time resolution
      reduces the need for exact contrast timing while also providing dynamic
      information. Spatial resolution is determined primarily by the projection readout
      resolution and is thus isotropic across the FOV, which is also isotropic.
      Although undersampling the outer regions of k-space introduces aliased energy
      into the image, which may compromise resolution, this is not a limiting factor in
      high-contrast applications such as MRA. Results from phantom and volunteer
      studies are presented demonstrating isotropic resolution, broad coverage with an
      isotropic field of view (FOV), minimal projection reconstruction artifacts, and
      temporal information. In one application, a single breath-hold exam covering the
      entire pulmonary vasculature generates high-resolution, isotropic imaging volumes
      depicting the bolus passage.

PMID- 12210940
TI  - Multiecho segmented EPI with z-shimmed background gradient compensation (MESBAC)
      pulse sequence for fMRI.
AB  - A MultiEcho Segmented EPI with z-shimmed BAckground gradient Compensation
      (MESBAC) pulse sequence is proposed and validated for functional MRI (fMRI) study
      in regions suffering from severe susceptibility artifacts. This sequence provides
      an effective tradeoff between spatial and temporal resolution and reduces image
      distortion and signal dropout. The blood oxygenation level-dependent (BOLD)
      weighted fMRI signal can be reliably obtained in the region of the orbitofrontal
      cortex (OFC). To overcome physiological motion artifacts during prolonged
      multisegment EPI acquisition, two sets of navigator echoes were acquired in both
      the readout and phase-encoding directions. Ghost artifacts generally produced by
      single-shot EPI acquisition were eliminated by separately placing the even and
      odd echoes in different k-space trajectories. Unlike most z-shim methods that
      focus on increasing temporal resolution for event-related functional brain
      mapping, the MESBAC sequence simultaneously addresses problems of image
      distortion and signal dropout while maintaining sufficient temporal resolution.
      The MESBAC sequence will be particularly useful for pharmacological and affective
      fMRI studies in brain regions such as the OFC, nucleus accumbens, amygdala,
      parahippocampus, etc.

PMID- 12210941
TI  - Mapping the fiber orientation in articular cartilage at rest and under pressure
      studied by 2H double quantum filtered MRI.
AB  - The one-dimensional (2)H double quantum filtered (DQF) spectroscopic imaging
      technique was used to study the orientation of collagen fibers in articular
      cartilage. The method detects only water molecules in anisotropic environments,
      which in cartilage is caused by their interaction with the collagen fibers. A
      large quadrupolar splitting was observed in the calcified zone and a smaller
      splitting in the radial zone. In the transitional zone the splitting was not
      resolved and a small splitting was again detected in the superficial zone. From
      measurements performed at two orientations of the plug relative to the magnetic
      field it was deduced that in the calcified and radial zones the fibers are
      oriented perpendicular to the bone, bending at the transitional zone and
      flattening at the superficial zone. The effect of load applied to the cartilage
      bone plug was monitored by the same technique. At low loads there is a small
      decrease in the quadrupolar splitting in the calcified zone, a marked decrease in
      the radial zone, and an increase of the splitting accompanied by a thickening of
      the superficial zone. Under high loads, while the thickening and the splitting of
      the superficial zone further increase, the splitting in the radial and calcified
      zones completely collapse. Pressure-induced changes in the thickness of the
      surface zone indicate flattening of the collagen fibers near the surface. The
      marked collapse of the splitting near the bone at high pressures may result from
      crimping of the collagen fibers.

PMID- 12210942
TI  - Detection and modeling of non-Gaussian apparent diffusion coefficient profiles in
      human brain data.
AB  - This work details the observation of non-Gaussian apparent diffusion coefficient
      (ADC) profiles in multi-direction, diffusion-weighted MR data acquired with
      easily achievable imaging parameters (b approximately 1000 s/mm(2)). A technique
      is described for modeling the profile of the ADC over the sphere, which can
      capture non-Gaussian effects that can occur at, for example, intersections of
      different tissue types or white matter fiber tracts. When these effects are
      significant, the common diffusion tensor model is inappropriate, since it is
      based on the assumption of a simple underlying diffusion process, which can be
      described by a Gaussian probability density function. A sequence of models of
      increasing complexity is obtained by truncating the spherical harmonic (SH)
      expansion of the ADC measurements at several orders. Further, a method is
      described for selection of the most appropriate of these models, in order to
      describe the data adequately but without overfitting. The combined procedure is
      used to classify the profile at each voxel as isotropic, anisotropic Gaussian, or
      non-Gaussian, each with reference to the underlying probability density function
      of displacement of water molecules. We use it to show that non-Gaussian profiles
      arise consistently in various regions of the human brain where complex tissue
      structure is known to exist, and can be observed in data typical of clinical
      scanners. The performance of the procedure developed is characterized using
      synthetic data in order to demonstrate that the observed effects are genuine.
      This characterization validates the use of our method as an indicator of
      pathology that affects tissue structure, which will tend to reduce the complexity
      of the selected model.

PMID- 12210943
TI  - Ventilation-perfusion ratio of signal intensity in human lung using oxygen
      enhanced and arterial spin labeling techniques.
AB  - This study investigates the distribution of ventilation-perfusion (V/Q) signal
      intensity (SI) ratios using oxygen-enhanced and arterial spin labeling (ASL)
      techniques in the lungs of 10 healthy volunteers. Ventilation and perfusion
      images were simultaneously acquired using the flow-sensitive alternating
      inversion recovery (FAIR) method as volunteers alternately inhaled room air and
      100% oxygen. Images of the T(1) distribution were calculated for five volunteers
      for both selective (T(1f)) and nonselective (T(1)) inversion. The average T(1)
      was 1360 ms +/- 116 ms, and the average T(1f) was 1012 ms +/- 112 ms, yielding a
      difference that is statistically significant (P < 0.002). Excluding large
      pulmonary vessels, the average V/Q SI ratios were 0.355 +/- 0.073 for the left
      lung and 0.371 +/- 0.093 for the right lung, which are in agreement with the
      theoretical V/Q SI ratio. Plots of the V/Q SI ratio are similar to the
      logarithmic normal distribution obtained by multiple inert gas elimination
      techniques, with a range of ratios matching ventilation and perfusion. This MRI
      V/Q technique is completely noninvasive and does not involve ionized radiation. A
      limitation of this method is the nonsimultaneous acquisition of perfusion and
      ventilation data, with oxygen administered only for the ventilation data.

PMID- 12210944
TI  - Perfusion quantification using Gaussian process deconvolution.
AB  - The quantification of perfusion using dynamic susceptibility contrast MRI (DSC
      MRI) requires deconvolution to obtain the residual impulse response function
      (IRF). In this work, a method using the Gaussian process for deconvolution (GPD)
      is proposed. The fact that the IRF is smooth is incorporated as a constraint in
      the method. The GPD method, which automatically estimates the noise level in each
      voxel, has the advantage that model parameters are optimized automatically. The
      GPD is compared to singular value decomposition (SVD) using a common threshold
      for the singular values, and to SVD using a threshold optimized according to the
      noise level in each voxel. The comparison is carried out using artificial data as
      well as data from healthy volunteers. It is shown that GPD is comparable to SVD
      with a variable optimized threshold when determining the maximum of the IRF,
      which is directly related to the perfusion. GPD provides a better estimate of the
      entire IRF. As the signal-to-noise ratio (SNR) increases or the time resolution
      of the measurements increases, GPD is shown to be superior to SVD. This is also
      found for large distribution volumes.

PMID- 12210946
TI  - Single-point (constant-time) imaging in radiofrequency Fourier transform electron
      paramagnetic resonance.
AB  - This study describes the use of the single-point imaging (SPI) modality, also
      known as constant-time imaging (CTI), in radiofrequency (RF) Fourier transform
      (FT) electron paramagnetic resonance (EPR). The SPI technique, commonly used for
      high-resolution solid-state nuclear magnetic resonance (NMR) imaging, has been
      successfully applied to 2D and 3D RF-FT-EPR imaging of phantoms containing narrow
      line EPR spin probes. The SPI scheme is essentially a phase-encoding technique
      that operates by acquiring a single data point in the free induction decay (FID)
      after a fixed delay (phase-encoding time), following the pulsed RF excitation, in
      the presence of static magnetic field gradients. Since the phase-encoding time
      remains constant for a given image data set, the spectral information is
      automatically deconvolved, providing well-resolved pure spatial images.
      Therefore, images obtained using SPI are artifact-free and the resolution is not
      significantly limited by the line width, compared to the images obtained using
      the conventional filtered back-projection (FBP) scheme, suggesting that the SPI
      modality may have advantages for EPR imaging of large objects. In this work the
      advantages and limitations of SPI as compared to FBP are investigated by imaging
      suitable phantom objects. Although SPI takes longer to perform than the FBP
      method, optimization of the data collection scheme may increase the temporal
      resolution, rendering this technique suitable for in vivo studies. Spectral
      information can also be extracted from a series of SPI images that are generated
      as a function of the delay from the excitation pulse.

PMID- 12210945
TI  - Polarization of the RF field in a human head at high field: a study with a
      quadrature surface coil at 7.0 T.
AB  - The RF field intensity distribution in the human brain becomes inhomogeneous due
      to wave behavior at high field. This is further complicated by the spatial
      distribution of RF field polarization that must be considered to predict image
      intensity distribution. An additional layer of complexity is involved when a
      quadrature coil is used for transmission and reception. To study such complicated
      RF field behavior, a computer modeling method was employed to investigate the RF
      field of a quadrature surface coil at 300 MHz. Theoretical and experimental
      results for a phantom and the human head at 7.0 T are presented. The results are
      theoretically important and practically useful for high-field quadrature coil
      design and application.

PMID- 12210947
TI  - Volume tracking cardiac 31P spectroscopy.
AB  - The limited reliability and accuracy of cardiac spectroscopy have been partly
      attributed to effects from respiratory motion. In this work, we developed a
      prospective volume tracking method for respiratory motion compensation based on
      multiple navigator echoes and demonstrated its application in cardiac (31)P
      spectroscopy. The sequence consists of two 2D selective excitation pulses
      preceding the spectroscopic experiment to sample respiratory motion components.
      The navigator information is evaluated in real-time to calculate the shift of the
      heart from respiration. Based on the displacement information, the spectroscopic
      volume and/or grid position is prospectively corrected to track the volume of
      interest. The method was validated with a moving compartment phantom simulating
      in vivo respiratory motion. With volume tracking, no signal contamination was
      apparent. Spectra obtained in 14 healthy volunteers were evaluated using time
      domain fitting procedures. The fitting accuracy improved consistently with volume
      tracking compared to data from non-navigated reference acquisitions. Compared to
      other gating approaches available for spectroscopy, the current technique does
      not degrade the scan efficiency, thus allowing effective use of scan time.

PMID- 12210948
TI  - On the timing characteristics of the apparent diffusion coefficient contrast in
      fMRI.
AB  - For the past 10 years, functional MRI (fMRI) has seen rapid progress in both
      clinical and basic science research. Most of the imaging techniques are based on
      the blood oxygenation level-dependent (BOLD) contrast which arises from the field
      perturbation of the paramagnetic deoxyhemoglobin due to the mismatch between the
      local oxygen demand and delivery. Because the changes of oxygenation level take
      place mostly in the veins, the dominant signal sources of the BOLD signal are
      intra- and extravascular proton pools of the veins. Perfusion imaging methods,
      developed parallel to the BOLD technique, seek to quantify the blood flow and
      perfusion. Recently, perfusion imaging using arterial spin tagging methods have
      been used to study brain function by investigating the changes of the blood flow
      and perfusion during brain activation, thereby generating an alternative contrast
      mechanism to the functional brain imaging. Since most of these methods require
      tagging pulse and wait time for blood to be delivered to the imaged slice, the
      temporal resolution may not be optimal. Dynamic intravoxel incoherent motion
      (IVIM) weighting schemes using apparent diffusion coefficient (ADC) contrast were
      suggested to image the relative changes of the in-plane blood flow during brain
      function. In this report, it was demonstrated that, in addition to the spatial
      discrepancies of the activated areas, the time course based on the ADC contrast
      consistently precedes that from the BOLD contrast with timing offset on the order
      of 1 sec. Since arterial networks would have different spatial locations and
      preceding temporal characters, the findings in this report are indicative that
      the ADC contrast is sensitive to the arterial blood flow changes.

PMID- 12210949
TI  - MRI cardiac tagging using a sinc-modulated RF pulse train.
AB  - A method of spatial modulation of magnetization using the RF pulse train is
      described for improved cardiac tagging. The method is based on a sinc-modulated
      RF pulse train in the presence of constant gradient. Such an RF pulse train
      yields a rectangular profile of saturated magnetization, and the bandwidth of the
      sinc envelope controls the width of the saturation tag. Compared to DANTE and
      SPAMM tagging techniques, this method offers sharper-edged tags and the ability
      to change the ratio of tag width to tag separation. The approach was implemented
      on a 9.4 T vertical bore NMR system and demonstrated with both phantom and in
      vivo mouse heart studies.

PMID- 12210950
TI  - Study of the effect of CSF suppression on white matter diffusion anisotropy
      mapping of healthy human brain.
AB  - Healthy human brain diffusion anisotropy maps derived from standard spin echo
      diffusion tensor imaging (DTI) were compared with those using fluid-attenuated
      inversion recovery (FLAIR) preparation prior to DTI to null the signal from
      cerebrospinal fluid (CSF). Consistent comparisons entailed development of DTI
      postprocessing methods, image masking based on fitting quality, and an objective
      region-of-interest-based method for assessment of white matter extent. FLAIR DTI
      achieved an extended delineation of major white-matter tracts (genu, splenium,
      and body of the corpus callosum) close to large CSF-filled spaces (lateral
      ventricles), but did not affect representation of tracts remote from CSF
      (internal and external capsules and coronal radiation). This result, which was
      detectable qualitatively (visual inspection), was verified quantitatively by
      analyses of the relative anisotropy (RA) distribution over white matter
      structures for 11 subjects. FLAIR DTI thus suppresses the CSF signal that
      otherwise masks underlying anisotropic parenchymal tissue through partial volume
      averaging.

PMID- 12210951
TI  - MR tagging early after myocardial infarction in mice demonstrates contractile
      dysfunction in adjacent and remote regions.
AB  - The purpose of this study was to use MR myocardial tagging to assess regional
      cardiac function after myocardial infarction (MI) in mice. Eight mice were imaged
      before and 1 day after MI. MRI included cine imaging, myocardial tagging, and
      contrast-enhanced imaging. Regional percent circumferential shortening (%CS) was
      measured from the tagged images, and the region of hyperenhancement on the
      contrast-enhanced images was used to determine the infarcted, adjacent, and
      remote zones. Ejection fraction (EF) fell from 59% +/- 6% at baseline to 32% +/-
      6% after MI (P < 0.01). At baseline, %CS was 14.5% +/- 3.4%. After MI, %CS was
      0.7% +/- 4.4% in the infarcted zone, 7.4% +/- 4.4% in the adjacent zone, and
      11.8% +/- 4.2% in the remote zone. %CS was statistically different for all
      comparisons between the infarcted, adjacent, remote, and baseline groups (P <
      0.01). MR tagging can detect regional differences in myocardial function post-MI
      in mice.

PMID- 12210953
TI  - Superresolution in MRI?

PMID- 12210952
TI  - Characterization and reduction of gradient-induced eddy currents in the RF shield
      of a TEM resonator.
AB  - Radiofrequency (RF) shields that surround MRI transmit/receive coils should
      provide effective RF screening, without introducing unwanted eddy currents
      induced by gradient switching. Results are presented from a detailed examination
      of an effective RF shield design for a prototype transverse electromagnetic (TEM)
      resonator suitable for use at 3 Tesla. It was found that effective RF shielding
      and low eddy current sensitivity could be achieved by axial segmentation (gap
      width = 2.4 mm) of a relatively thick (35 microm) copper shield, etched on a
      kapton polyimide substrate. This design has two main advantages: first, it makes
      the TEM less sensitive to the external environment and RF interference; and
      second, it makes the RF shield mechanically robust and easy to handle and
      assemble.

PMID- 12210956
TI  - Purification and characterization of a digestive alkaline protease from the
      larvae of Spilosoma obliqua.
AB  - A digestive protease from Spilosoma obliqua (Lepidoptera: Arctiidae) fifth instar
      larval guts was purified and characterized. The protease was purified using
      ammonium sulfate fractionation, ion-exchange chromatography, and hemoglobin
      sepharose affinity chromatography. The purification procedure resulted in a 37
      fold increase in the specific activity of the protease. Protease thus obtained
      was found to be electrophoretically pure under native and denaturing conditions.
      The purified protease had a molecular mass of 90 kDa as determined by gel
      filtration, and a pH optimum of 11.0. The purified protease optimally hydrolyzed
      casein at 50 degrees C. A Km of 2 x10(-6) M was obtained using BApNA as a
      substrate for the purified alkaline protease. The ability of S. obliqua protease
      and bovine trypsin to hydrolyze various synthetic substrates (BApNA, BAEE, and
      BAME), and the inhibition patterns of S. obliqua and bovine trypsin with
      "classical" trypsin inhibitors are also reported.

PMID- 12210957
TI  - Co-development of Encarsia formosa (Hymenoptera: Aphelinidae) and the greenhouse
      whitefly, Trialeurodes vaporariorum (Homoptera: Aleyrodidae): a histological
      examination.
AB  - Using histological techniques, we have simultaneously examined the co-development
      of the Aphelinid parasitoid Encarsia formosa and its host the greenhouse
      whitefly, Trialeurodes vaporariorum. Previously we have determined that
      regardless of the whitefly instar parasitized, parasitoid larvae would not molt
      to their final instar until the whitefly reaches its maximum dimensions. In
      unparasitized T. vaporariorum, this point in development corresponds to the
      initiation of the adult molt. In part, this study was conducted to determine the
      developmental state of parasitized whiteflies at the time they achieve their
      maximum dimensions. It was found that parasitized final instar T. vaporariorum
      do, in fact, undergo a final molt and that E. formosa larvae will not molt to
      their final instar until this has occurred. The timing of the final whitefly molt
      appears unaffected by parasitization. The commonly observed melanization of
      parasitized whiteflies appears to be a consequence of this molt. In addition, we
      have discovered that the adult wasp oviposits within the ventral ganglion of the
      whitefly, and that major organ systems of the whitefly persist very late into
      parasitoid development. We also report the presence of possible endosymbiotic
      bacteria residing in the fatbody of E. formosa.

PMID- 12210958
TI  - Analysis of involvement of the 3'-untranslated regions in regulating mRNA
      stability for vitellogenin, cyanoprotein alpha, and cyanoprotein beta from the
      bean bug, Riptortus clavatus.
AB  - The degradation of the 3'-untranslated regions (UTRs) of vitellogenin,
      cyanoprotein alpha, and cyanoprotein beta from the bean bug, Riptortus clavatus,
      was analyzed in vitro. The degradation pattern was similar for all three RNAs,
      with a high degradation rate in non-diapausing adult insects and no degradation
      in the fifth instar nymphs and in diapausing adults, and was not correlated with
      the expression levels of these three proteins. Proteins binding to the 3'-UTRs
      were detected in polysomal and cytosolic extracts. These factors, however, were
      present in all developmental stages. The abundance of the polysomal factor showed
      little variation, but the cytosolic factor was enriched in adult insects. Cross
      competition experiments demonstrated that the same factors bound to all three
      RNAs with similar affinity. The pattern of degradation, presence of the binding
      factors in all stages, and their inability to distinguish between the target
      sequences indicate that the 3'-UTRs do not participate in controlling the
      expression of these three proteins.

PMID- 12210959
TI  - Purification and characterization of acetylcholinesterase from cotton aphid
      (Aphis gossypii Glover).
AB  - A simple and effective method was set up to purify acetylcholinesterase (AChE,
      EC3.1.1.7) from the cotton aphid, Aphis gossypii Glover. The procedure involved
      filtration on a sephadex G-25 column, separation with sephadex G-200 and
      procainamide affinity column. AChE from both susceptible and resistant strains
      were purified to a single band as resolved on denaturing polyacrylamide gel
      electrophoresis (SDS-PAGE). The specific activity increased by 35,100- and 33,680
      fold with a yield of 30.3 and 29.8%, respectively. The molecular mass of the
      purified AChE was about 63,500 Dalton as determined by SDS-PAGE. However, three
      bands resolved on PAGE gel electrophoresis, leading to the inference that native
      AChE exists in three forms. The optimum conditions for measuring the activity of
      purified AChE with kinetic method were 0.02M phosphate buffer, pH7.2, 0.02 mM
      5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), and 25 degrees C. Investigation also
      revealed that crude extract and purified AChE had different kinetic
      characteristics and inhibitory properties. They responded differently to varied
      DTNB, ATChI, and phosphate buffer ion concentrations, as well as pH, temperature,
      and inhibitors. The purified AChE was more sensitive to eserine, methamidophos,
      and pirimicarb. Especially for resistant aphids, the sensitivity of purified AChE
      to methamidophos and pirimicarb was enhanced 6.43 and 11.73 times, respectively.
      We infer that one or more factors in the crude extract from the resistance strain
      have more influence on AChE sensitivity. Further study is needed to investigate
      the basis of these observations.

PMID- 12210960
TI  - Eicosanoids mediate Manduca sexta cellular response to the fungal pathogen
      Beauveria bassiana: a role for the lipoxygenase pathway.
AB  - Many studies have documented the involvement of eicosanoids in insect cellular
      immune responses to bacteria. The use of the fungal pathogen Beauveria bassiana
      as a nodulation elicitor, with inhibition of phospholipase A(2) by dexamethasone,
      extends the principle to fungi. This study also provides the first evidence of
      involvement of the lipoxygenase (LOX) pathway rather than the cyclooxygenase
      (COX) pathway in synthesis of the nodulation mediating eicosanoid(s). The LOX
      product, 5(S)-hydroperoxyeicosa-6E,8Z,11Z,14Z-tetraenoic acid (5-HPETE),
      substantially reversed nodulation inhibition caused by dexamethasone and the LOX
      inhibitors, caffeic acid and esculetin. The COX product, prostaglandin H(2)
      (PGH(2)), did not reverse the nodulation inhibition by dexamethasone or the COX
      inhibitor, ibuprofen. None of the inhibitors tested had a significant effect on
      the phagocytosis of B. bassiana blastospores in vitro. Hemocyte phenoloxidase
      activity was reduced by dexamethasone, esculetin, and the COX inhibitor,
      indomethacin. The rescue candidates 5-HPETE and PGH(2) did not reverse the
      inhibition.

PMID- 12210961
TI  - Microsurgery, complex reconstruction, and fellowships.

PMID- 12210962
TI  - Lining the mouth floor with prelaminated fascio-mucosal free flaps: clinical
      experience.
AB  - Soft-tissue defects of the mouth floor need thin, foldable, and pliable tissues
      able to preserve local anatomy as well as chewing, phonation, and deglutition.
      The oral mucosa is made of a stratified, nonkeratinized, epithelium-secreting
      mucus, which lubricates the oral cavity and facilitates tongue movements. No flap
      exists that can reproduce the physiology of the oral mucosa better than the oral
      mucosa itself. Prefabrication of mucosal flaps may represent the best solution.
      Therefore, 10 consecutive cases of mouth floor cancer were treated with
      prelamination of the fascia antibrachialis with mucosal grafts obtained from the
      healthy cheek, and with subsequent transplantation 3 weeks later. A significant
      increase in mucosal graft surface was seen in all cases, with a mean size twice
      the original. All flaps healed uneventfully. Follow-up time ranged between 2-60
      months (average, 26.6 months). Morphological and functional results were
      excellent. Tongue motility, speech intelligibility, and swallowing were
      reestablished in all treated cases. Mucosal prelamination of the forearm fascia
      is feasible and allows physiological reconstruction of oral cavity defects up to
      6 x 4 cm.

PMID- 12210963
TI  - Lower limb replantations: indications and a new scoring system.
AB  - The need for reconstruction of lower limb amputations is increasing, due to high
      energy trauma in road accidents and work-related injuries. The indication for
      lower limb replantation is still controversial. Compared with upper limb
      replantations, indications are more select due to the frequent complications in
      lower limb salvage procedures, such as severe general complications or local
      complications such as necrosis, infections, nonunions, the need for secondary
      lengthening, or other reconstructive procedures. The satisfactory results given
      by artificial prosthesis, such as quicker recovery time and fewer secondary
      procedures, also contribute to the higher degree of selection for lower limb
      replantation candidates. Since 1993, we have replanted 14 amputations of the
      lower limb in 12 patients, including 2 bilateral cases. Although survival of the
      replanted segment was obtained in all patients, 5 cases were subsequently
      amputated for severe secondary complications. Of the remaining 9 cases, evaluated
      by means of Chen criteria, 7 had good results (3 Chen I and 4 Chen II), 1
      sufficient (Chen III), and 1 poor (Chen IV). The best results were obtained in
      young patients. Our experience led us to examine the necessity for careful,
      objective patient selection. We developed a score evaluation system by modifying
      the international classifying method for severe limb traumas (mangled extremity
      severity score, or MESS system). This relatively simple system, based on the
      retrospective study of our cases, considers several parameters (patient's age,
      general conditions, level and type of lesion, time of injury, and associated
      lesions), giving each one a score. The total score gives the indication for
      replantation, predicts the functional outcome, and facilitates decision-making.

PMID- 12210964
TI  - Microsurgical reconstruction of lower limb bone defects following tumor resection
      using vascularized fibula osteoseptocutaneous flap.
AB  - This study included 25 patients with lower limb tumors who had wide local
      resection and reconstruction by vascularized fibula osteoseptocutaneous flap, and
      who had their surgery performed at least 24 months before the end of the study.
      The average age at operation was 23.5 years. Twenty-three tumors were
      malignant;16 were staged as high-grade sarcomas (stage IIA, stage IIB, and
      Ewing's sarcoma). Tumor volume averaged 293.2 cc (range, 41.4-860). The resulting
      defect after tumor resection averaged 16 cm (range, 9-20 cm). The fibula was
      inserted as a single strut in 21 patients, and as a double-barrel construct in 4
      patients. Fixation was augmented by interlocking nail in 11 cases, bridge plate
      in 9 cases, and external fixator in 5 cases. Twenty-four (96%) flaps survived.
      All grafts united in an average period of 4.5 months (range, 3-8 months) after
      transfer. Two secondary procedures were necessary to achieve graft union. Full
      weight bearing was possible after an average period of 7.5 months (range, 5-14
      months). Significant hypertrophy (> or =30% of original fibular diameter)
      occurred in 85% of patients after an average period of 10 months from the index
      operation. In the latest follow-up radiographs (mean, 32 months), the degree of
      hypertrophy averaged 90% (range, 30-200%). Graft fracture occurred in three
      patients, and all healed conservatively. The Musculoskeletal Tumor Society rating
      score (MTSRS) averaged 21.2 points at the end of the first postoperative year,
      and 23.6 at the end of the study.

PMID- 12210965
TI  - Shoulder fusion and free-functioning gracilis transplantation in patients with
      elbow and shoulder paralysis caused by poliomyelitis.
AB  - Six children between 7-16 years of age presented with flail shoulder and elbow
      caused by poliomyelitis. Shoulder fusion was followed by free-functioning
      gracilis transplantation to replace the atrophied biceps muscle. The transplanted
      muscle was reinnervated by either the spinal accessory or phrenic nerve. Follow
      up averaged 44 months (range, 56-23 months). All cases developed at least grade 3
      power of elbow flexion and were able to place their hands to their mouths. Five
      out of 6 cases were able to flex their elbow against resistance. One case
      required tension readjustment, and elbow flexion contracture of 45 degrees
      developed in another case. On average, the transplanted gracilis started to
      contract 3 months after transplantation, and muscle power reached grade 2 at 5-6
      months and grade 3 at 9-12 months. Muscles supplied by the spinal accessory nerve
      were earlier to contract and ultimately attained more power than those supplied
      by the phrenic nerve, probably because of easier rehabilitation. Shoulder fusion
      and free-functioning gracilis transplantation for biceps replacement provide a
      solution for restoration of function in children with flail shoulder and elbow,
      as caused by poliomyelitis. The procedure can be useful in other neuromuscular
      conditions, such as late-presenting Erb's palsy, especially when no other muscles
      are available for local transfer.

PMID- 12210967
TI  - Improved renal transplantation in the rat with a nonsplinted ureteroureterostomy.
AB  - Orthotopic renal transplantation in the rat is a widely used model in immunology
      and transplantation-related research. Although numerous modifications of the
      surgical technique of ureteric reconstruction were evaluated, ureter
      complications following this reconstruction still occurred frequently. Instead of
      dividing the ureter in the middle between kidney and bladder (method 1), the
      anastomosis was performed close to the renal pelvis after cutting the ureter
      obliquely (method 2), which enlarged the diameter of the ureteral anastomosis 2
      fold. The incidence of stenosis of ureteric anastomosis was 12.5% (3/24) using
      method 1, whereas this complication was avoided completely (0/45) using method 2.
      Furthermore, the risk of injury to the ureter was reduced, as isolation of the
      ureter was limited. These modifications improved the last delicate step in the
      procedure of rat kidney transplantation.

PMID- 12210968
TI  - Facial contour restoration in Barraquer-Simons syndrome using two free TRAM
      flaps: Presentation of two case reports and long-term follow-up.
AB  - Barraquer-Simons syndrome, a disorder of unknown etiology, is characterized by a
      cephalothoracic lipodystrophy. We present 2 patients treated with a bilateral
      free transverse rectus abdominis myocutaneous (TRAM) flap to restore facial
      contour. Our technique of using a muscle component to fill the cheek defect was
      based on our experience with free muscle transfer in facial reanimation. In
      comparison with adipose tissue, muscle tissue does not show a tendency for ptosis
      because of its consistency and firm attachment of the muscle surface to the
      surrounding tissues. These cases demonstrate the possibility for the use of
      simultaneous dissection of the face and flaps, and the reliability of the
      vascular pedicle. The stability of the abdominal wall was secured by closure of
      the rectus sheath over Teflon mesh, which has been proven to prevent hernia. Our
      long-term follow-up demonstrates a stable symmetrical facial appearance.

PMID- 12210970
TI  - Rethinking justice.
AB  - Changes in the way people marry, bear children and live together, combined with
      the changing nature of support for families, has put pressure on the justice
      system to adjust to new family and community realities in order to accomplish
      justice goals. Although the entire legal system is implicated by the changing
      nature of families and communities, most scholars and practitioners have focused
      on the judicial system and those courts most relevant to family issues: namely,
      the juvenile, family, and criminal courts. As scholars and practitioners began to
      'rethink justice,' whole new reform movements of therapeutic jurisprudence,
      restorative justice, and community justice (among others) have emerged to offer
      new paradigms for the administration of justice. In this essay we discuss ways in
      which families and the justice system interact to strengthen and weaken each
      other to accomplish justice goals.

PMID- 12210971
TI  - From moral theory to penal attitudes and back: a theoretically integrated
      modeling approach.
AB  - From a moral standpoint, we would expect the practice of punishment to reflect a
      solid and commonly shared legitimizing framework. Several moral legal theories
      explicitly aim to provide such frameworks. Based on the theories of
      Retributivism, Utilitarianism, and Restorative Justice, this article first sets
      out to develop a theoretically integrated model of penal attitudes and then
      explores the extent to which Dutch judges' attitudes to punishment fit the model.
      Results indicate that penal attitudes can be measured in a meaningful way that is
      consistent with an integrated approach to moral theory. The general structure of
      penal attitudes among Dutch judges suggests a streamlined and pragmatic approach
      to legal punishment that is identifiably founded on the separate concepts central
      to moral theories of punishment. While Restorative Justice is frequently
      presented as an alternative paradigm, results show it to be smoothly incorporated
      within the streamlined approach.

PMID- 12210972
TI  - Apology in the criminal justice setting: evidence for including apology as an
      additional component in the legal system.
AB  - The criminal justice system has reached unprecedented scope in the United States,
      with over 6.4 million people under some type of supervision. Remedies that have
      the potential to reduce this number are continually being sought. This article
      analyzes an innovative strategy currently being reconsidered in criminal justice:
      the apology. Despite a legal system that only sporadically acknowledges it,
      evidence for the use of apology is supported by social science research, current
      criminal justice theories, case law, and empirical studies. Social psychological,
      sociological and socio-legal studies pinpoint the elements and function of
      apology, what makes apologies effective, and concerns about apology if it were
      implemented in the criminal justice system. Theoretical evidence is examined
      (including restorative justice, therapeutic jurisprudence, crime, shame, and
      reintegration) to explore the process of apology in the criminal justice context.
      Attribution theory and social conduct theory are used to explain the apology
      process specifically for victims and offenders. A brief examination of case law
      reveals that though apology has no formal place in criminal law, it has surfaced
      recently under the federal sentencing guidelines. Finally, empirical evidence in
      criminal justice settings reveals that offenders want to apologize and victims
      desire an apology. Moreover, by directly addressing the harmful act, apology may
      be the link to reduced recidivism for offenders, as well as empowerment for
      victims. This evidence combined suggests that apology is worthy of further study
      as a potentially valuable addition to the criminal justice process.

PMID- 12210973
TI  - Restorative justice innovations in Canada.
AB  - As many jurisdictions move towards more retributive measures as a means to
      address public discontent with crime, a parallel movement has developed in regard
      to restorative justice. This article presents three restorative initiatives
      currently in use in Canada. Each initiative addresses offender behavior and
      community engagement at a different point in the justice continuum. The use of
      Sentencing Circles is an example of how restorative justice principles can be
      instituted at the front end, prior to an offender becoming lodged in the system.
      The Restorative Justice Options to Parole Suspension project demonstrates how
      community engagement can assist in preventing offenders from being returned to
      the system once they have achieved conditional release. The Circles of Support
      and Accountability project has enlisted the support of professionally supported
      volunteers in the community reintegration of high-risk sexual offenders. These
      initiatives are presented within a framework of effective correctional
      interventions and increased empowerment for a variety of stakeholders.

PMID- 12210974
TI  - A teen court evaluation with a therapeutic jurisprudence perspective.
AB  - Teen court defendants were assessed on several attitudinal measures when they
      entered and when they completed their teen court program. Teen court volunteers
      and high school civics students in a control group were assessed on the same
      measures at two points in time that approximated the length of teen court
      involvement for defendants. Re-offense rates for defendants were assessed. In
      addition, defendants and their parents completed satisfaction surveys. The teen
      court experience did not significantly impact the attitudes and beliefs of either
      the defendants or the volunteers. The re-offense rate for defendants was 13%,
      which is similar to other teen court programs and less than the re-offense rate
      for the general diversion program in the county that was the target of the study.
      Since this teen court selected youth with the least serious delinquency activity
      (primarily shoplifting), conclusions about the program's effectiveness in
      reducing further offending cannot be made. Defendants and their parents reported
      high levels of satisfaction with their teen court experience but defendants
      became more alienated from institutional authority. This study did not support
      the teen court experience as having a generally beneficial impact on defendants
      or volunteers that would be expected from a therapeutic jurisprudence
      perspective.

PMID- 12210975
TI  - The effects of defendant remorse on mock juror decisions in a malpractice case.
AB  - The purpose of this study was to observe the effects of defendant remorse on
      monetary damages awarded to a plaintiff in a malpractice case. In two
      experiments, the physician-defendant expressed remorse at the time of the
      incident and again at trial, expressed remorse at trial, explicitly demonstrated
      a lack of remorse at trial, or made no mention of remorse (or a lack thereof).
      Participants decided how much money to award to the plaintiff and evaluated both
      the plaintiff and the defendant on several dimensions. Participants awarded
      greater compensation when the physician expressed remorse at the time of the
      incident than in the other conditions, both when the plaintiff was the injured
      patient's spouse in a wrongful death suit (experiment 1) and when the patient
      sued on his own behalf (experiment 2). This effect of remorse was greater for
      males than for females (experiment 1) and for relatively severely injured
      plaintiffs (experiment 2).

PMID- 12210976
TI  - Achieving community justice through faith-based initiatives.
AB  - Prior to 1996, most churches and other faith-based organizations were ineligible
      to receive federal funding for community services. In a little noticed provision
      of the Welfare Reform Act of 1996 known as 'charitable choice,' the federal
      government allowed religious groups to receive money for social programs without
      requiring them to censor their religious expression or give up their religious
      identity. States, with varying degrees of vigor and success, have partnered with
      faith-based organizations to provide community services that serve the purpose of
      transitioning people from welfare to work. Recent political developments and
      legislation suggest an expanded role for faith-based organizations to receive
      federal money to develop community services, including money for community
      justice projects. The Comment begins with an overview of the political and legal
      contexts that allow the development of promoting community justice initiatives
      through faith-based efforts. Next, there is a discussion of practical
      considerations that influence decisions of churches and faith-based organizations
      to participate in these activities. Finally, there is discussion of the roles
      social scientists and others might play to facilitate community justice
      initiatives through faith-based efforts.

PMID- 12210977
TI  - Effects of mood and emotion on juror processing and judgments.
AB  - This study explored the influence of mood and emotion on mock-jurors' processing
      of testimonial inconsistencies, perceptions of witness credibility and offender
      culpability, and verdicts. Jurors' mood and testimonial consistency were
      manipulated using a simulated trial with a 2 (mood: sad/neutral) x 2 (testimonial
      consistency: consistent/inconsistent) between-groups design. Sad mood resulted in
      more accurate reporting of testimonial inconsistencies, a finding consistent with
      previous research indicating more substantive processing in association with sad
      mood. Direct relationships between veridicality and number of inconsistencies
      detected and mock-juror judgments were also observed. Although anger was not
      experimentally manipulated, the data suggest that trial circumstances which
      arouse anger in jurors may impair processing and also bias their judgments of
      witnesses and defendants. Possible directions for research on mood and emotion in
      the courtroom context are suggested.

PMID- 12210979
TI  - Mechanisms of protein folding: molecular chaperones and their application in
      biotechnology.

PMID- 12210980
TI  - G-protein subunit dissociation is not an integral part of G-protein action.

PMID- 12210981
TI  - Carbohydrate microarrays.

PMID- 12210983
TI  - On the transformation of (S)-2-hydroxypropylphosphonic acid into fosfomycin in
      Streptomyces fradiae--a unique method of epoxide ring formation.
AB  - (1S,2S)- and (1R,2S)-2-hydroxy-[1-D(1)]propylphosphonic acid were synthesised
      from (1S,2S)-2-benzyloxy-[1-D(1)]propanol, which was obtained by horse liver
      alcohol dehydrogenase catalysed reduction of the corresponding aldehyde. When
      (1S,2S)-2-hydroxy-[1-D(1)]propylphosphonic acid was fed to Streptomyces fradiae,
      the deuterium was retained to the same extent in fosfomycin (cis-epoxide) and its
      co-metabolite trans-epoxide. Removal of the hydrogen (deuterium) atom from the C
      1 atom of deuterated 2-hydroxypropylphosphonic acids is a stereospecific process
      (the hydrogen atom of (S)-2-hydroxypropylphosphonic acid is pro-R). The formation
      of the O--C-1 bond of fosfomycin occurs with net inversion of configuration, the
      formation of the O--C-1 bond of the trans-epoxide with net retention.

PMID- 12210982
TI  - Probing biomolecular interactions of glutathione transferase M2-2 by using
      peptide phage display.
AB  - The interactions between biomolecules and human glutathione transferase M2-2 (GST
      M2-2) were probed by using 9- and 15-mer combinatorial peptide libraries
      displayed on phage. The peptide libraries were based on random DNA sequences
      fused to gIII, a gene that expresses a phage coat protein and thus causes the
      peptides to be displayed on the surface of phage particles. A peptide sequence
      was enriched through binding to GST M2-2, which indicated a successful selection.
      Binding studies with the peptide displayed on phage showed binding specificity.
      The sequence of the peptide had similarities to segments of proteins in the Swiss
      Prot Database, to c-Jun N-terminal kinase (JNK), and to the protein Bcl3. JNK is
      linked to the regulation of the transcription factor AP-1. Use of cell-based
      assays of the transcriptional activity of AP-1 allowed a novel coactivation
      function of GST M2-2 to be demonstrated. Specificity in the activation was
      indicated by the lack of effect of GST A1-1. No coactivator function of GST M2-2
      could be demonstrated in assays with Bcl3. These results suggest that GST M2-2
      has biological roles in addition to catalysis of detoxication reactions, and
      demonstrate the potential of phage display in functional genomics research.

PMID- 12210984
TI  - Inhibition of adhesion of type 1 fimbriated Escherichia coli to highly
      mannosylated ligands.
AB  - The inhibitory potencies of a number of mannosides, di- and trivalent mannosides,
      a set of mannose-terminating dendrimers, and five types of mannose-bearing
      neoglycoproteins were determined by using a binding assay that measures the
      binding of (125)I-labeled, highly mannosylated neoglycoprotein to a type 1
      fimbriated Escherichia coli (K12) strain in suspension. The IC(50) values (the
      concentration of inhibitor that causes 50 % reduction in the bound (125)I-ligand
      to E. coli) obtained by this method were much lower than the equivalent values
      obtained by hemagglutination or in assays that involve microplate immobilization.
      Two important factors that strongly influence the affinity to E. coli adhesin
      are: 1) the presence of an alpha-oriented aglycon that has a long aliphatic chain
      or an aromatic group immediately next to the glycosyl oxygen, and 2) the presence
      of multiple mannosyl residues that can span a distance of 20 nm or longer on a
      relatively inflexible structure. The two best inhibitors, which are a highly
      mannosylated neoglycoprotein with the longest linking arm between a mannose and
      protein amino group and the largest mannosylated dendrimer (fourth generation),
      exhibited sub-nM IC(50) values.

PMID- 12210985
TI  - Mutants of 4-oxalocrotonate tautomerase catalyze the decarboxylation of
      oxaloacetate through an imine mechanism.
AB  - A designed single amino acid substitution can alter the catalytic activity and
      mechanism of 4-oxalocrotonate tautomerase (4-OT). While the wild-type enzyme
      catalyzes only the tautomerization of oxalocrotonate, the Pro1Ala mutant (P1A)
      catalyzes two reactions--the original tautomerization reaction and the
      decarboxylation of oxaloacetate. Although the N-terminal amine group of P1A is
      involved in both reactions, our results support a nucleophilic mechanism for the
      decarboxylase activity, in contrast to the general acid/base mechanism that has
      been previously established for the tautomerase activity. These findings
      demonstrate that a single catalytic group in a 4-OT mutant can catalyze two
      reactions by two different mechanisms.

PMID- 12210986
TI  - Combinatorial synthesis of new cationic lipids and high-throughput screening of
      their transfection properties.
AB  - Here we describe the first synthesis-screening approach for the identification
      and optimization of new cationic lipids for gene transfer in various cell lines.
      Combinatorial solid-phase chemistry was used to synthesize a library of new
      cationic lipids based on 3-methylamino-1,2-dihydroxypropane as the polar,
      cationic lipid part. As the nonpolar lipid part, different hydrocarbon chains
      were bound to the amino group of the scaffold and the amino group was further
      methylated to afford constantly cationic lipids. Lipids were synthesized in both
      configurations and as racemates, and the counter ions were also varied. By using
      a fully automated transfection screening method and COS-7 cells, the cationic
      lipid N,N-ditetradecyl-N-methyl-amino-2,3-propanediol (KL-1-14) was identified as
      a candidate lipid for the development of an improved transfection reagent.
      Screening the transfection properties of KL-1-14 in numerous combinations with
      the helper lipids dioleoylphosphatidylethanolamine (DOPE) and cholesterol (Chol)
      revealed that Chol is the most suitable helper lipid and the best KL-1-14/Chol
      ratio is 0.5-0.7. Compared to the standard transfection lipid N-[1-(2,3
      dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl sulfate (DOTAP), transfection
      efficiency was improved by a factor of about 40. Furthermore, by using R- and S
      configured KL-1-14, it could be shown that the configuration of the lipids had no
      significant influence on its transfection efficiency. The highest transfection
      efficiencies were achieved with chloride as the counter ion. The new lipofection
      reagent was further tested to transfect the cell lines MDA-MB-468, MCF-7, MDCK
      C7, and primary dentritic cells (DC), which are important for the development of
      new anticancer gene therapy strategies. Even in these cells, KL-1-14/Chol (1:0.6)
      had improved transfection efficiencies, which were about two to four times higher
      than for DOTAP.

PMID- 12210987
TI  - Selection of small-molecule mediators of the RNA regulation of PKR, the RNA
      dependent protein kinase.
AB  - The RNA-dependent protein kinase (PKR) is a component of the interferon antiviral
      response and a member of the class of RNA-binding proteins with a double-stranded
      RNA binding motif. PKR is activated when it binds to double-stranded RNA (dsRNA)
      or viral replicative intermediates that comprise dsRNA and this activation
      results in the inhibition of protein synthesis. Some viruses circumvent this
      activity through the synthesis of highly structured decoy RNAs that bind PKR and
      block activation. Small-molecule mediators of the binding of PKR to these RNA
      inhibitors would be useful tools to further define the importance of specific PKR
      RNA complexes in vivo and may possess antiviral activity. Here we investigate the
      ability of a library of structurally diverse peptide-acridine conjugates (PACs)
      to target a complex formed between the dsRNA binding domain (dsRBD) of PKR and a
      viral RNA inhibitor. We used a novel screening method based on the cleavage of
      RNA ligands with ethylenediaminetetraacetic acid.Fe modified protein. The
      selection revealed a PAC (9-anilinoacridine-4-Hyp-Nap-Nap, where Hyp is trans-4
      hydroxyproline and Nap is 1-napthylalanine), able to inhibit the binding of the
      PKR dsRBD to RNA with an IC(50) value of 10 +/- 5 microM. Furthermore, the
      structural requirements for inhibition by the selected PAC were substantiated in
      an independent PKR activation assay. We found that the potency of inhibition by
      an intercalating ligand can be increased by the introduction of a substituent
      that does not increase the overall charge of the molecule. This result is
      important for the design of inhibitors of PKR-RNA binding that function inside
      living cells.

PMID- 12210988
TI  - Specificity studies of bacillus 1,3-1,4-beta-glucanases and application to
      glycosynthase-catalyzed transglycosylation.
AB  - Bacillus 1,3-1,4-beta-glucanases hydrolyze 1,3-1,4-beta-gluco-oligosaccharides
      with a retaining mechanism. The binding-site cleft of these endoglycosidases is
      composed of six subsites (-4 to +2) of which subsite -3 makes the largest
      contribution to transition state stabilization. The specificity of this subsite
      is here analyzed for both glycosidase and glycosynthase activities in the wild
      type and the nucleophile-less E134A mutant Bacillus licheniformis enzymes. A D
      galactosyl residue on the nonreducing end of a trisaccharide substrate is
      accepted by the enzyme and binds at subsite -3 in the productive enzyme-substrate
      complex. The wild-type enzyme catalyzes the hydrolysis of the substrate
      Glcbeta4Glcbeta3GlcbetaMU (Glc=glucosyl, MU=4-methylumbelliferyl) with a
      k(cat)/K(M) value only 1.3-fold higher than for the Galbeta4Glcbeta3GlcbetaMU
      (Gal=galactosyl) substrate. The corresponding alpha-fluorides act as good donors
      for the glycosynthase condensation reaction with mono- and disaccharide acceptors
      catalyzed by the E134A mutant. Whereas self-condensation and elongation products
      are also obtained as minor compounds with the Glcbeta4Glcbeta3GlcalphaF donor,
      nearly quantitative yields of single condensation products are obtained with the
      Galbeta4Glcbeta3GlcalphaF donor, in which the axial configuration of the 4-OH
      group on the nonreducing end prevents self-condensation and elongation reactions.

PMID- 12210989
TI  - Aspartyl phosphonates and phosphoramidates: the first synthetic inhibitors of
      bacterial aspartate-semialdehyde dehydrogenase.
AB  - The synthesis of methylene phosphonate, difluoromethylene phosphonate and
      phosphoramidate analogues of aspartyl phosphate, together with reduced analogues,
      is described. These compounds were shown to be effective inhibitors of aspartate
      semialdehyde dehydrogenase (ASA-DH) from Escherichia coli. However, despite the
      structural similarity of the compounds, different patterns of inhibition were
      observed, indicative of two phases of recognition and binding. Correlation
      between measured inhibition constants with pK(a) values supports the theory that
      binding at the phosphate binding site is optimised for singly ionised phosphate
      analogues.

PMID- 12210990
TI  - Receptor-dependence of the transcription read-out in a small-molecule three
      hybrid system.
AB  - Small-molecule three-hybrid systems show promise as an in vivo alternative to
      affinity chromatography for detecting small-molecule-protein interactions. While
      several three-hybrid systems have been reported, little has been done to
      characterize these systems and, in particular, to test the assumption that the
      protein-small-molecule interaction can be varied without disrupting the
      transcription read-out. Recently we reported a dexamethasone-methotrexate
      chemical inducer of dimerization (CID) for use in the yeast three-hybrid system,
      based on the well-studied ligand-receptor pairs dexamethasone (Dex)
      glucocorticoid receptor (GR) and methotrexate (Mtx)-dihydrofolate reductase
      (DHFR). Here we describe our first efforts to characterize this system, by
      focusing on a comparison of the activity of a bacterial and a mammalian DHFR as a
      test case of the influence of the ligand-receptor pair on the transcription read
      out. By using a lacZ reporter gene, the activity of several GR and DHFR protein
      chimeras with different orientations and linker sequences and Dex-Mtx CIDs with
      different chemical linkers have been compared. In addition, Western analyses and
      in vivo biochemical assays have been carried out to confirm the integrity of the
      GR and DHFR protein chimeras. The transcription read-out is found to be much more
      sensitive to the structure of the protein chimeras than the CID. The most
      surprising result is that the levels of transcription activation are consistently
      higher with the bacterial than the mammalian DHFR, despite the fact that both
      proteins bind Mtx with an inhibition constant (K(I)) in the low pM range. These
      results set the stage for understanding three-hybrid systems at the biochemical
      level so that they can be used to detect ligand-receptor pairs with a range of
      structures and dissociation constants.

PMID- 12210991
TI  - Purine-based inhibitors of inositol-1,4,5-trisphosphate-3-kinase.

PMID- 12210993
TI  - Binding and docking of synthetic heterotrimeric collagen type IV peptides with
      alpha1beta1 integrin.

PMID- 12210992
TI  - Solution- and solid-phase synthesis of the polybasic lipid-modified C termini of
      Rho A and K-Ras 4B.

PMID- 12210994
TI  - Computational studies of subtilisin-catalyzed transesterification of sucrose:
      importance of entropic effects.

PMID- 12210996
TI  - Salt-promoted protein folding, preferential binding, or electrostatic screening?
AB  - The extended coil/molten globule conformational equilibrium exhibited by
      ferricytochrome c in 10 to 20 mM HCl was examined using free boundary capillary
      electrophoresis. Addition of the osmolyte glucitol, also called sorbitol, to
      shift the conformational equilibrium toward the molten globule markedly
      diminished the mobility of the protein. This diminution can be entirely assigned
      to the relative viscosity of the added glucitol. The insensitivity of the
      viscosity corrected protein mobility to added glucitol suggests that both the
      extended coil and molten globule conformations of cytochrome c are free draining
      in an electrophoresis measurement. Addition of a neutral salt to shift the
      conformational equilibrium toward the molten globule conformation also markedly
      diminished the mobility of the protein. This diminution can be entirely assigned
      to the electrostatic screening afforded by the added salt. The onset of the
      conformational transition observed by optical measurements and the onset of
      electrostatic screening observed by mobility measurements appear to be in common
      for some but not all neutral salts. The exception suggests that preferential
      binding of the anion of a neutral salt to the molten globule conformation and not
      electrostatic screening is principally responsible for the shift in the
      conformational equilibrium of cytochrome c in acidic solutions.

PMID- 12210997
TI  - Combining the GOR V algorithm with evolutionary information for protein secondary
      structure prediction from amino acid sequence.
AB  - We have modified and improved the GOR algorithm for the protein secondary
      structure prediction by using the evolutionary information provided by multiple
      sequence alignments, adding triplet statistics, and optimizing various
      parameters. We have expanded the database used to include the 513 non-redundant
      domains collected recently by Cuff and Barton (Proteins 1999;34:508-519; Proteins
      2000;40:502-511). We have introduced a variable size window that allowed us to
      include sequences as short as 20-30 residues. A significant improvement over the
      previous versions of GOR algorithm was obtained by combining the PSI-BLAST
      multiple sequence alignments with the GOR method. The new algorithm will form the
      basis for the future GOR V release on an online prediction server. The average
      accuracy of the prediction of secondary structure with multiple sequence
      alignment and full jack-knife procedure was 73.5%. The accuracy of the prediction
      increases to 74.2% by limiting the prediction to 375 (of 513) sequences having at
      least 50 PSI-BLAST alignments. The average accuracy of the prediction of the new
      improved program without using multiple sequence alignments was 67.5%. This is
      approximately a 3% improvement over the preceding GOR IV algorithm (Garnier J,
      Gibrat JF, Robson B. Methods Enzymol 1996;266:540-553; Kloczkowski A, Ting K-L,
      Jernigan RL, Garnier J. Polymer 2002;43:441-449). We have discussed alternatives
      to the segment overlap (Sov) coefficient proposed by Zemla et al. (Proteins
      1999;34:220-223).

PMID- 12210998
TI  - Non-native interactions, effective contact order, and protein folding: a
      mutational investigation with the energetically frustrated hydrophobic model.
AB  - By Monte Carlo simulations, we explored the effect of single mutations on the
      thermodynamics and kinetics of the folding of a two-dimensional, energetically
      frustrated, hydrophobic protein model. Phi-Value analysis, corroborated by
      simulations beginning from given sets of judiciously chosen initial contacts,
      suggests that the transition state of the model consists of a limited region of
      the native structure, that is, a folding nucleus. It seems that the most
      important contacts in the transition state (large and positive Phi) are not the
      ones with the highest contact order, because in this case the entropic cost of
      their formation would be too high, but exactly the ones that decrease the
      entropic cost of difficult contacts, reducing their effective contact order.
      Mutations of internal monomers involved in high-order contacts were actually the
      ones resulting in the fastest kinetics (and Phi < 0), indicating they tend to
      make low order, non-native contacts of low entropic cost that stabilize the
      unfolded state with respect to the transition state. Folding acceleration by
      other non-native interactions was also observed and a simple general mechanism is
      proposed according to which non-native contacts can act indirectly over the
      folding nucleus, "chelating" out potentially harmful contacts. The polymer graph
      of our model, which facilitates the visualization of effective contact orders,
      successfully suggests the relative kinetic importance of different contacts and
      is reasonably consistent with analogous graphs for the well characterized family
      of SH3 domains.

PMID- 12210999
TI  - Structural parameterization of the binding enthalpy of small ligands.
AB  - A major goal in ligand and drug design is the optimization of the binding
      affinity of selected lead molecules. However, the binding affinity is defined by
      the free energy of binding, which, in turn, is determined by the enthalpy and
      entropy changes. Because the binding enthalpy is the term that predominantly
      reflects the strength of the interactions of the ligand with its target relative
      to those with the solvent, it is desirable to develop ways of predicting enthalpy
      changes from structural considerations. The application of structure/enthalpy
      correlations derived from protein stability data has yielded inconsistent results
      when applied to small ligands of pharmaceutical interest (MW < 800). Here we
      present a first attempt at an empirical parameterization of the binding enthalpy
      for small ligands in terms of structural information. We find that at least three
      terms need to be considered: (1) the intrinsic enthalpy change that reflects the
      nature of the interactions between ligand, target, and solvent; (2) the enthalpy
      associated with any possible conformational change in the protein or ligand upon
      binding; and, (3) the enthalpy associated with protonation/deprotonation events,
      if present. As in the case of protein stability, the intrinsic binding enthalpy
      scales with changes in solvent accessible surface areas. However, an accurate
      estimation of the intrinsic binding enthalpy requires explicit consideration of
      long-lived water molecules at the binding interface. The best statistical
      structure/enthalpy correlation is obtained when buried water molecules within 5-7
      A of the ligand are included in the calculations. For all seven protein systems
      considered (HIV-1 protease, dihydrodipicolinate reductase, Rnase T1,
      streptavidin, pp60c-Src SH2 domain, Hsp90 molecular chaperone, and bovine beta
      trypsin) the binding enthalpy of 25 small molecular weight peptide and nonpeptide
      ligands can be accounted for with a standard error of +/-0.3 kcal x mol(-1).

PMID- 12211000
TI  - Molecular motions and conformational changes of HPPK.
AB  - 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) belongs to a class of
      catalytic enzymes involved in phosphoryl transfer and is a new target for the
      development of novel antimicrobial agents. In the present study, the fundamental
      consideration is to view the overall structure of HPPK as a network of
      interacting residues and to extract the most cooperative collective motions that
      define its global dynamics. A coarse-grained model, harmonically constrained
      according to HPPK's crystal structure is used. Four crystal structures of HPPK
      (one apo and three holo forms with different nucleotide and pterin analogs) are
      studied with the goal of providing insights about the function-dynamic
      correlation and ligand induced conformational changes. The dynamic differences
      are examined between HPPK's apo- and holo-forms, because they are involved in the
      catalytic reaction steps. Our results indicate that the palm-like structure of
      HPPK is nearly rigid, whereas the two flexible loops: L2 (residues 43-53) and L3
      (residues 82-92) exhibit the most concerted motions for ligand recognition and
      presumably, catalysis. These two flexible loops are involved in the recognition
      of HPPKs nucleotide and pterin ligands, whereas the rigid palm region is
      associated with binding of these cognate ligands. Six domains of collective
      motions are identified, comprised of structurally close but not necessarily
      sequential residues. Two of these domains correspond to the flexible loops (L2
      and L3), whereas the remaining domains correspond to the rigid part of the
      molecule.

PMID- 12211001
TI  - Natural coordinate representation for the protein backbone structure.
AB  - A new model for describing the geometry of the C(alpha) backbone atoms in protein
      molecules is derived. This model uses one continuous variable per amino acid.
      This is half the number of degrees-of-freedom used in traditional backbone
      models. The new model was tested on 721 PDB structures and its average accuracy
      was determined to be 1.14 A cRMSD. This model can be used as a description of
      local structure that provides higher resolution than the traditional secondary
      structure categories. Also, because this structure description is one
      dimensional, it can be used to align structures with the same efficiency and
      convergence properties available in the popular sequence alignment tools.
      Furthermore, the 1:1 correspondence with the amino acid sequence has implications
      for combined sequence/structure alignment. Conventional secondary structure
      prediction was used to further reduce the number of degrees-of-freedom in 16 test
      proteins. In those cases, the average cRMSD degraded from 0.96 to 2.33 A while
      the number of degrees-of-freedom improved (reduced) by more than 30%.

PMID- 12211002
TI  - Impact of incorporating the 2C5 crystal structure into comparative models of
      cytochrome P450 2D6.
AB  - Cytochrome P450 2D6 (CYP2D6) metabolizes approximately one third of the drugs in
      current clinical use. To gain insight into its structure and function, we have
      produced four different sets of comparative models of 2D6: one based on the
      structures of P450s from four different microorganisms (P450 terp, P450 eryF,
      P450 cam, and P450 BM3), another on the only mammalian P450 (2C5) structure
      available, and the other two based on alternative amino acid sequence alignments
      of 2D6 with all five of these structures. Principal component analysis suggests
      that inclusion of the 2C5 crystal structure has a profound effect on the modeling
      process, altering the general topology of the active site, and that the models
      produced differ significantly from all of the templates. The four models of 2D6
      were also used in conjunction with molecular docking to produce complexes with
      the substrates codeine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP);
      this identified Glu 216 [in the F-helix; substrate recognition site (SRS) 2] as a
      key determinant in the binding of the basic moiety of the substrate. Our studies
      suggest that both Asp 301 and Glu 216 are required for metabolism of basic
      substrates. Furthermore, they suggest that Asp 301 (I-helix, SRS-4), a residue
      thought from mutagenesis studies to bind directly to the basic moiety of
      substrates, may play a key role in positioning the B'-C loop (SRS-1) and that the
      loss of activity on mutating Asp 301 may therefore be the result of an indirect
      effect (movement of the B'-C loop) on replacing this residue.

PMID- 12211003
TI  - Evaluating CASP4 predictions with physical energy functions.
AB  - Physical energy scoring functions based on implicit solvation models are tested
      by evaluating predictions from the most recent CASP4 competition. The best
      performing scoring functions are identified along with the best protocol for
      preparing structures before energies are evaluated. Ranking of structures with
      the best scoring functions is compared across CASP4 targets to establish when
      physical scoring functions can be expected to reliably distinguish structures
      that are most similar to the native fold in a set of misfolded or unfolded
      protein conformations. The results are used to interpret previous studies where
      scoring functions were tested on the standard decoy sets by Park, Levitt, and
      Baker. We show that the best physical scoring functions can be applied
      successfully in automated consensus scoring applications where a single best
      conformation has to be selected from a set of structures from different sources.
      Finally, the potential for better protein structure scoring functions is
      discussed with a suggestion for an empirically parameterized linear combination
      of energy components.

PMID- 12211004
TI  - Anisotropic effective interactions in a coarse-grained tube picture of proteins.
AB  - Recent studies have shown that a coarse-grained description of a protein backbone
      represented as a tube of non-zero thickness captures many of the common
      characteristics of small globular proteins. Here we argue that such a physical
      picture leads to a prediction of inherently anisotropic amino acid interactions.
      In order to test this prediction, we have carried out an extensive analysis of a
      data bank made up of 600 proteins with low sequence homology and covering many
      different three-dimensional folds. This analysis, based on the study of the
      geometrical properties of the vectors joining next-nearest neighbor C(alpha)
      atoms along the chain, shows clearly that when amino acids are in contact, the
      distribution of their relative orientations is not random but exhibits peaks at
      specific angles whose values reflect, in general, the tubular nature of proteins
      and, more specifically, the nature of the secondary structure motifs, which are
      the building blocks of protein structures. Our results suggest that the
      incorporation of the relative orientation of amino acids in contact could play a
      vital role in simplified coarse-grained schemes for determining effective
      interaction parameters for use in folding, threading, and docking.

PMID- 12211005
TI  - Role of C-terminal region of Staphylococcal nuclease for foldability, stability,
      and activity.
AB  - The role of the C-terminal region of Staphylococcal nuclease (SNase) was examined
      by deletion mutation. Deletions up to eight residues do not affect the structure
      and function. The structure and enzymatic activity were partially lost by
      deleting Ser141-Asn149 (Delta141-149), and deletion of Trp140-Asn149 (Delta140
      149) resulted in further loss of structure and activity. A 13-residue deletion
      showed the same effect as the 10-residue deletion. Both Ser141Gln and Ser141Ala
      mutations for an eight-residue deletion mutant did not alter properties as well
      as Ser141A1a for full-length SNase. In contrast, Trp140Ala mutation for Delta141
      149 shows the same effect as the deletion of Trp140. Trp140Ala mutation for full
      length SNase causes the loss of native structure. These observations indicate the
      significance of the 140th and the 141st residues. The side-chain of the 140th
      residue is required to be tryptophan; however, the backbone of the 141st residue
      is solely critical for foldability, but the side-chain information is not
      crucial. All of the mutants that take a non-native conformation show enzymatic
      activity and inhibitor-induced folding, suggesting that foldability is required
      for the activity.

PMID- 12211006
TI  - Discriminative ability with respect to amino acid types: assessing the
      performance of knowledge-based potentials without threading.
AB  - We present a novel method designed to analyze the discriminative ability of
      knowledge-based potentials with respect to the 20 residue types. The method is
      based on the preference of amino acids for specific types of protein environment,
      and uses a virtual mutagenesis experiment to estimate how much information a
      given potential can provide about environments of each amino acid type. This
      allows one to test and optimize the performance of real potentials at the level
      of individual amino acids, using actual data on residue environments from a
      dataset of known protein structures. We have applied our method to long-range and
      medium-range pairwise distance-dependent potentials. The results of our study
      indicate that these potentials are only able to discriminate between a very
      limited number of residue types, and that discriminative ability is extremely
      sensitive to the choice of parameters used to construct the potentials, and even
      to the size of the training dataset. We also show that different types of
      pairwise distance potentials are dominated by different types of interactions.
      These dominant interactions strongly depend on the type of approximation used to
      define residue position. For each potential, our methodology is able to identify
      a potential-specific amino acid distance matrix and a reduced amino acid alphabet
      of any specified size, which may have implications for sequence alignment and
      multibody models.

PMID- 12211007
TI  - Crystal structure of MTH169, a crucial component of
      phosphoribosylformylglycinamidine synthetase.

PMID- 12211008
TI  - NMR structure of the Escherichia coli protein YacG: a novel sequence motif in the
      zinc-finger family of proteins.

PMID- 12211010
TI  - Variability in the pKa of histidine side-chains correlates with burial within
      proteins.
AB  - Acidic pKas of histidines buried within the protein interior are frequently
      rationalized on the contradictory basis of either polar interactions within the
      protein or the effects of a hydrophobic environment. To examine these
      relationships, we surveyed the buried surface area, depth of burial, polar
      interactions, and crystallographic temperature factors of histidines of known
      pKa. It has been found that buried environments of histidines do not always
      result in acidic pKas. Instead, the variability of histidine pKas increases for
      residues where the majority of the side-chain is buried. Because buried
      histidines are always found in mixed polar/apolar environments, multiple
      environmental contributions to pKa values must be considered. However, the
      quantitative relationships between heterogeneous environments and pKa values are
      not immediately apparent from the available data.

PMID- 12211011
TI  - Information-theoretic dissection of pairwise contact potentials.
AB  - Pairwise contact potentials have a long, successful history in protein structure
      prediction. They provide an easily-estimated representation of many attributes of
      protein structures, such as the hydrophobic effect. In order to improve on
      existing potentials, one should develop a clear understanding of precisely what
      information they convey. Here, using mutual information, we quantified the
      information in amino acid potentials, and the importance of hydropathy, charge,
      disulfide bonding, and burial. Sampling error in mutual information was
      controlled for by estimating how much information cannot be attributed to
      sampling bias. We found the information in amino acid contacts to be modest: 0.04
      bits per contact. Of that, only 0.01 bits of information could not be attributed
      to hydropathy, charge, disulfide bonding, or burial.

PMID- 12211012
TI  - Distinguishing foldable proteins from nonfolders: when and how do they differ?
AB  - When a denatured polypeptide is put into refolding conditions, it undergoes
      conformational changes on a variety of times scales. We set out here to
      distinguish the fast events that promote productive folding from other processes
      that may be generic to any non-folding polypeptide. We have apply an ab initio
      folding algorithm to model the folding of various proteins and their
      compositionally identical, random-sequence analogues. In the earliest stages,
      proteins and their scrambled-sequence counterparts undergo indistinguishable
      reductions in the extent to which they explore conformation space. For both
      polypeptides, an early contraction occurs but does not involve the formation of a
      distinct intermediate. Following this phase, however, the naturally-occurring
      sequences are distinguished by an increase in the formation of three-body
      correlations wherein a hydrophobic group desolvates and protects an intra
      molecular hydrogen bond. These correlations are manifested in a mild but
      measurable reduction of the accessible configuration space beyond that of the
      random-sequence peptides, and portend the folding to the native structure. Hence,
      early events reflect a generic response of the denatured ensemble to a change in
      solvent condition, but the wild-type sequence develops additional correlations as
      its structure evolves that can reveal the protein's foldability.

PMID- 12211013
TI  - Conformational states of the glucocorticoid receptor DNA-binding domain from
      molecular dynamics simulations.
AB  - Molecular dynamics simulations (MD) have been performed on variant crystal and
      NMR-derived structures of the glucocorticoid receptor DNA-binding domain (GR
      DBD). A loop region five residues long, the so-called D-box, exhibits significant
      flexibility, and transient perturbations of the tetrahedral geometry of two
      structurally important Cys4 zinc finger are seen, coupled to conformational
      changes in the D-box. In some cases, one of the Cys ligands to zinc exchanges
      with water, although no global distortion of the protein structure is observed.
      Thus, from MD simulation, dynamics of the D-box could partly be explained by
      solvent effects in conjunction with structural reformation of the zinc finger.

PMID- 12211014
TI  - Cys(x)His(y)-Zn2+ interactions: thiol vs. thiolate coordination.
AB  - In zinc proteins, the Zn2+ cation frequently binds with a tetrahedral
      coordination to cysteine and histidine side chains, for example, in many DNA
      binding proteins, where it plays primarily a structural role. We examine the
      possibility of thiolate protonation in Cys(x)His(y)-Zn2+ groups, both in proteins
      and in solution, through a combination of theoretical calculations and database
      analysis. Seventy-five percent of the thiolate-coordinated zincs in the Cambridge
      Structural Database are tetrahedral, while di-alkanethiol coordination always
      involves five or more ligands. Ab initio quantum calculations are performed on
      (ethanethiol/thiolate)(3)imidazole-Zn2+ complexes in vacuum, yielding geometries
      and gas phase basicities. Protonating one (respectively two) thiolates increases
      the Zn-S(thiol) distance by 0.4 A (respectively 0.3 A), providing a structural
      marker for protonation. The stabilities of the complexes in solution are compared
      by combining the gas phase basicities with continuum dielectric solvation
      calculations. In a continuum solvent with permittivity epsilon = 4, 20, or 80,
      one of three thiolates is predicted to be protonated at neutral pH. By extension,
      Cys4-Zn2+ groups are expected to be protonated in the same conditions. In
      contrast, most Cys3His and Cys4 geometries in the Protein Data Bank (PDB) appear
      consistent with all-thiolate Zn2+ coordination. This apparent discrepancy is
      resolved by two recent surveys of zinc protein structures, which suggest that
      these all-thiolate sites are stabilized by charged and polar groups nearby in the
      protein, thus overcoming their intrinsic instability. However, the experimental
      resolution is not sufficient in all the PDB structures to rule out a
      thiol/thiolate mixture, and protonated thiolates may occur in some proteins not
      solved at high resolution or not represented in the PDB, as suggested by recent
      mass spectrometry experiments; this possibility should be allowed for in X-ray
      structure refinement.

PMID- 12211015
TI  - Crystal structures of unligated and CN-ligated Glycera dibranchiata monomer
      ferric hemoglobin components III and IV.
AB  - Erythrocytes of the marine annelid, Glycera dibranchiata, contain a mixture of
      monomeric and polymeric hemoglobins. There are three major monomer hemoglobin
      components, II, III, IV (also called GMH2, 3, and 4), that have been highly
      purified and well characterized. We have now crystallized GMH3 and GMH4 and
      determined their structures to 1.4-1.8 A resolution. The structures were
      determined for these two monomer hemoglobins in the oxidized (Fe3+, ferric, or
      met-) forms in both the unligated and cyanide-ligated states. This work differs
      from two published, refined structures of a Glycera dibranchiata monomer
      hemoglobin, which has a sequence that is substantially different from any bona
      fide major monomer hemoglobins (GMH2, 3, or 4). The high-resolution crystal
      structures (presented here) and the previous NMR structure of CO-ligated GMH4,
      provide a basis for interpreting structure/function details of the monomer
      hemoglobins. These details include: (1) the strong correlation between
      temperature factor and NMR dynamics for respective protein forms; (2) the unique
      nature of the HisE7Leu primary sequence substitutions in GMH3 and GMH4 and their
      impact on cyanide ion binding kinetics; (3) the LeuB10Phe difference between GMH3
      and GMH4 and its impact on ligand binding; and (4) elucidation of changes in the
      structural details of the distal and proximal heme pockets upon cyanide binding.

PMID- 12211016
TI  - Inhibitor binding alters the directions of domain motions in HIV-1 reverse
      transcriptase.
AB  - Understanding the molecular mechanisms of HIV-1 reverse transcriptase (RT) action
      and drug inhibition is essential for designing effective antiretroviral
      therapies. Although comparisons of the different crystal forms of RT give
      insights into the flexibility of different domains, a direct computational
      assessment of the effect of inhibitor binding on the collective dynamics of RT is
      lacking. A structure-based approach is used here for exploring the dynamics of RT
      in unliganded and inhibitor-bound forms. Non-nucleoside RT inhibitors (NNRTI) are
      shown to interfere directly with the global hinge-bending mechanism that controls
      the cooperative motions of the p66 fingers and thumb subdomains. The net effect
      of nevirapine binding is to change the direction of domain movements rather than
      suppress their mobilities. The second generation NNRTI, efavirenz, on the other
      hand, shows the stronger effect of simultaneously reorienting domain motions and
      obstructing the p66 thumb fluctuations. A second hinge site controlling the
      global rotational reorientations of the RNase H domain is identified, which could
      serve as a target for potential inhibitors of RNase H activity.

PMID- 12211017
TI  - Prediction of an HMG-box fold in the C-terminal domain of histone H1: insights
      into its role in DNA condensation.
AB  - In eukaryotes, histone H1 promotes the organization of polynucleosome filaments
      into chromatin fibers, thus contributing to the formation of an important
      structural framework responsible for various DNA transaction processes. The H1
      protein consists of a short N-terminal "nose," a central globular domain, and a
      highly basic C-terminal domain. Structure prediction of the C-terminal domain
      using fold recognition methods reveals the presence of an HMG-box-like fold. We
      recently showed by extensive site-directed and deletion mutagenesis studies that
      a 34 amino acid segment encompassing the three S/TPKK motifs, within the C
      terminal domain, is responsible for DNA condensing properties of H1. The position
      of these motifs in the predicted structure corresponds exactly to the DNA-binding
      segments of HMG-box-containing proteins such as Lef-1 and SRY. Previous analyses
      have suggested that histone H1 is likely to bend DNA bound to the C-terminal
      domain, directing the path of linker DNA in chromatin. Prediction of the
      structure of this domain provides a framework for understanding the higher order
      of chromatin organization.

PMID- 12211018
TI  - Design and folding of dimeric proteins.
AB  - In a similar way in which the folding of single-domain proteins provides an
      important test in the study of self-organization, the folding of homodimers
      constitutes a basic challenge in the quest for the mechanisms that are the basis
      of biological recognition. Dimerization is studied by following the evolution of
      two identical 20-letter amino acid chains within the framework of a lattice model
      and using Monte Carlo simulations. It is found that when design (evolution
      pressure) selects few, strongly interacting (conserved) amino acids to control
      the process, a three-state folding scenario follows, where the monomers first
      fold forming the halves of the eventual dimeric interface independently of each
      other, and then dimerize ("lock and key" kind of association). On the other hand,
      if design distributes the control of the folding process on a large number of
      (conserved) amino acids, a two-state folding scenario ensues, where dimerization
      takes place at the beginning of the process, resulting in an "induced type" of
      association. Making use of conservation patterns of families of analogous dimers,
      it is possible to compare the model predictions with the behavior of real
      proteins. It is found that theory provides an overall account of the experimental
      findings.

PMID- 12211019
TI  - Effects of a helix substitution on the folding mechanism of bovine alpha
      lactalbumin.
AB  - The structure, stability, and unfolding-refolding kinetics of a chimeric protein,
      in which the amino acid sequence of the flexible loop region (residues 105-110)
      comes from equine lysozyme and the remainder of the sequence comes from bovine
      alpha-lactalbumin were studied by circular dichroism spectroscopy and stopped
      flow measurements, and the results were compared with those of bovine alpha
      lactalbumin. The substitution of the flexible loop in bovine alpha-lactalbumin
      with the helix D of equine lysozyme destabilizes the molten globule state,
      although the native state is significantly stabilized by substitution of the
      flexible loop region. The kinetic refolding and unfolding experiments showed that
      the chimeric protein refolds significantly faster and unfolds substantially
      slower than bovine alpha-lactalbumin. To characterize the transition state
      between the molten globule and the native states, we investigated the guanidine
      hydrochloride concentration dependence of the rate constants of refolding and
      unfolding. Despite the significant differences in the stabilities of both the
      molten globule and native states between the chimeric protein and bovine alpha
      lactalbumin, the free energy level of the transition state is not affected by the
      amino acid substitution in the flexible loop region. Our results suggest that the
      destabilization in the molten globule state of the chimeric protein is caused by
      the disruption of the non-native interaction in the flexible loop region and that
      the disruption of the non-native interaction reduces the free energy barrier of
      refolding. We conclude that the non-native interaction in the molten globule
      state may act as a kinetic trap for the folding of alpha-lactalbumin.

PMID- 12211020
TI  - Thermal folding and mechanical unfolding pathways of protein secondary
      structures.
AB  - Mechanical stretching of secondary structures is studied through molecular
      dynamics simulations of a Go-like model. Force versus displacement curves are
      studied as a function of the stiffness and velocity of the pulling device. The
      succession of stretching events, as measured by the order in which contacts are
      ruptured, is compared to the sequencing of events during thermal folding and
      unfolding. Opposite cross-correlations are found for an alpha-helix and a beta
      hairpin structure. In a tandem of two alpha-helices, the two constituent helices
      unravel nearly simultaneously. A simple condition for simultaneous versus
      sequential unraveling of repeat units is presented.

PMID- 12211021
TI  - Folding and stretching in a Go-like model of titin.
AB  - Mechanical stretching of the I27 domain of titin and of its double and triple
      repeats are studied through molecular dynamics simulations of a Go-like model
      with Lennard-Jones contact interactions. We provide a thorough characterization
      of the system and correlate the sequencing of the folding and unraveling events
      with each other and with the contact order. The roles of cantilever stiffness and
      pulling rate are studied. Unraveling of tandem titin structures has a serial
      nature. The force-displacement curves in this coarse-grained model are similar to
      those obtained through all atom calculations.

PMID- 12211022
TI  - Understanding protein structure-function relationships in Family 47 alpha-1,2
      mannosidases through computational docking of ligands.
AB  - Family 47 alpha-1,2-mannosidases are crucial enzymes involved in N-glycan
      maturation in the endoplasmic reticula and Golgi apparati of eukaryotic cells.
      High-resolution crystal structures of the human and yeast endoplasmic reticulum
      alpha-1,2-mannosidases have been recently determined, the former complexed with
      the inhibitors 1-deoxymannojirimycin and kifunensine, both of which bind in its
      active site in the unusual 1C4 conformation. However, unambiguous identification
      of the catalytic proton donor and nucleophile involved in glycoside bond
      hydrolysis was not possible from this structural information. In this work, alpha
      D-galactose, alpha-D-glucose, and alpha-D-mannose were computationally docked in
      the active site in the energetically stable 4C1 conformation as well as in the
      1C4 conformation to compare their interaction energetics. From these docked
      structures, a model for substrate and conformer selectivity based on the
      dimensions of the active site was proposed. Alpha-D-galactopyranosyl-(1-->2)
      alpha-D-mannopyranose, alpha-D-glucopyranosyl-(1-->2)-alpha-D-mannopyranose, and
      alpha-D-mannopyranosyl-(1-->2)-alpha-D-mannopyranose were also docked into the
      active site with their nonreducing-end residues in the 1C4 and E4 (representing
      the transition state) conformations. Based on the docked structure of alpha-D
      mannopyranosyl-E4-(1-->2)-alpha-D-mannopyranose, the catalytic acid and base are
      Glu132 and Glu435, respectively.

PMID- 12211023
TI  - Structure of 2C-methyl-D-erythrol-2,4-cyclodiphosphate synthase from Haemophilus
      influenzae: activation by conformational transition.

PMID- 12211024
TI  - Crystal structure of the YciO protein from Escherichia coli.

PMID- 12211025
TI  - Crystal structure of thy1, a thymidylate synthase complementing protein from
      Thermotoga maritima at 2.25 A resolution.

PMID- 12211026
TI  - Completion and refinement of 3-D homology models with restricted molecular
      dynamics: application to targets 47, 58, and 111 in the CASP modeling competition
      and posterior analysis.
AB  - A method is presented to refine models built by homology by the use of restricted
      molecular dynamics (MD) techniques. The basic idea behind this method is the use
      of structure validation software to determine for each residue the likelihood
      that it is modeled correctly. This information is used to determine constraints
      and restraints in an MD simulation including explicit solvent molecules, which is
      used for model refinement. The procedure is based on the idea that residues that
      the validation software identifies as correctly positioned should be strongly
      constrained or restrained in the MD simulations, whereas residues that are likely
      to be positioned wrongly should move freely. Two different protocols are
      compared: one (applied to CASP3 target T58) using full structural constraints
      with separate optimization of each short fragment and the other (applied to T47)
      allowing some freedom using harmonic restraining potentials, with automatic
      optimization of the whole molecule. Structures along the MD trajectory that
      scored best in structural checks were selected for the construction of models
      that appeared to be successful in the CASP3 competition. Model refinement with MD
      in general leads to a model that is less like the experimental structure (Levitt
      et al. Nature Struct Biol 1999;6:108-111). Actually, refined T47 was slightly
      improved compared to the starting model; changes in model T58 led not to further
      enhancement. After the X-ray structure of the modeled proteins became known, the
      procedure was evaluated for two targets (T47 and the CASP4 target T111) by
      comparing a long simulation in water with the experimental target structures. It
      was found that structural improvements could be obtained on a nanosecond time
      scale by allowing appropriate freedom in the simulation. Structural checks
      applied to fast fluctuations do not appear to be informative for the correctness
      of the structure. However, both a simple hydrogen bond count and a simple
      compactness measure, if averaged over times of typically 300 ps, correlate well
      with structural correctness and we suggest that criteria based on these
      properties may be used in computational folding strategies.

PMID- 12211027
TI  - Optimization of a new score function for the generation of accurate alignments.
AB  - The accuracy of the alignments of protein sequences depends on the score matrix
      and gap penalties used in performing the alignment. Most score functions are
      designed to find homologs in the various databases rather than to generate
      accurate alignments between known homologs. We describe the optimization of a
      score function for the purpose of generating accurate alignments, as evaluated by
      using a coordinate root-mean-square deviation (RMSD)-based merit function. We
      show that the resulting score matrix, which we call STROMA, generates more
      accurate alignments than other commonly used score matrices, and this difference
      is not due to differences in the gap penalties. In fact, in contrast to most of
      the other matrices, the alignment accuracies with STROMA are relatively
      insensitive to the choice of gap penalty parameters.

PMID- 12211028
TI  - Mapping pathways of allosteric communication in GroEL by analysis of correlated
      mutations.
AB  - An interesting example of an allosteric protein is the chaperonin GroEL. It
      undergoes adenosine 5'-triphosphate-induced conformational changes that are
      reflected in binding of adenosine 5'-triphosphate with positive cooperativity
      within rings and negative cooperativity between rings. Herein, correlated
      mutations in chaperonins are analyzed to unravel routes of allosteric
      communication in GroEL and in its complex with its co-chaperonin GroES. It is
      shown that analysis of correlated mutations in the chaperonin family can provide
      information about pathways of allosteric communication within GroEL and between
      GroEL and GroES. The results are discussed in the context of available
      structural, genetic, and biochemical data concerning short- and long-range
      interactions in the GroE system.

PMID- 12211029
TI  - 1.3-A resolution structure of human glutathione S-transferase with S-hexyl
      glutathione bound reveals possible extended ligandin binding site.
AB  - Cytosolic glutathione S-transferases (GSTs) play a critical role in xenobiotic
      binding and metabolism, as well as in modulation of oxidative stress. Here, the
      high-resolution X-ray crystal structures of homodimeric human GSTA1-1 in the apo
      form and in complex with S-hexyl glutathione (two data sets) are reported at 1.8,
      1.5, and 1.3A respectively. At this level of resolution, distinct conformations
      of the alkyl chain of S-hexyl glutathione are observed, reflecting the
      nonspecific nature of the hydrophobic substrate binding site (H-site). Also, an
      extensive network of ordered water, including 75 discrete solvent molecules,
      traverses the open subunit-subunit interface and connects the glutathione binding
      sites in each subunit. In the highest-resolution structure, three glycerol
      moieties lie within this network and directly connect the amino termini of the
      glutathione molecules. A search for ligand binding sites with the docking program
      Molecular Operating Environment identified the ordered water network binding
      site, lined mainly with hydrophobic residues, suggesting an extended ligand
      binding surface for nonsubstrate ligands, the so-called ligandin site. Finally,
      detailed comparison of the structures reported here with previously published X
      ray structures reveal a possible reaction coordinate for ligand-dependent
      conformational changes in the active site and the C-terminus.

PMID- 12211030
TI  - Aromatic side-chain interactions in proteins. I. Main structural features.
AB  - In a data set of 593 nonhomologous proteins from the PDB, we have analyzed the
      pairing of phenylalanine, tyrosine, tryptophan, and histidine residues with their
      closest aromatic partner. The frequency distribution of the shortest interatomic
      distance of partners is bimodal with a sharp peak at approximately 3.8 A and a
      wider one at a longer distance. Only the 3.8 A peak corresponds to direct ring
      ring interactions thus aromatic pairs. The aromatic pairs were separated into two
      classes, near-sequence pairs and far-sequence pairs. Near sequence pairs
      stabilize local structure, and far-sequence pairs stabilize tertiary structure.
      Far-sequence pairs (74% of all pairs) mainly bridge two beta-strands, followed by
      pairs that bridge a beta-strand and a helix, and pairs that bridge a beta-strand
      and a random coil structure. Pairs that bridge helices are rare. The secondary
      structure of the near-sequence pairs depends on the partner distance in the
      sequence. When the partners are 1, 3, or 4 residues apart in the sequence, pairs
      are mostly found in helical structures. When the partners are two apart, pairs
      are mostly found in the same beta-strand. Analysis of the frequency of near
      sequence pairs supports the hypothesis that aromatic pairing occurs after, rather
      than before, the formation of secondary structures.

PMID- 12211031
TI  - Aromatic side-chain interactions in proteins. II. Near- and far-sequence Phe-X
      pairs.
AB  - We have collected all aromatic pairs (3152) involving an N-phenyl partner in a
      dataset of 593 proteins of the PDB: 728 of these pairs involve a partner residue
      less than 6 apart in the sequence. These near-sequence Phe-X pairs correspond to
      specific conformations that stabilize secondary structures, mainly alpha-helices
      when the residues are 1, 3, and 4 apart, and beta-strands when they are 2 apart
      in the sequence. These conformations are not spatially random and have been
      examined in detail. The remaining phenylalanine pairs (2424) are between partners
      more than 5 apart in the sequence. Of these far-sequence pairs, 34% of
      occurrences are in sheets. Next in frequencies are pairs that bridge a beta
      strand to a helix (24%), followed by pairs that bridge a beta-strand to a random
      coiled structure (15%). Helix to helix pairs only constitute 12% of these far
      sequence pairs. Analysis of the pairing frequency supports the hypothesis that
      aromatic interactions are late events of protein folding.

PMID- 12211032
TI  - Stability of macromolecular complexes.
AB  - Macromolecular interactions are crucial in numerous biologic processes, yet few
      general principles are available that establish firm expectations for the
      strength of these interactions or the expected contribution of specific forces.
      The simplest principle would be a monotonic increase in interactions as the size
      of the interface grows. The exact relationship might be linear or nonlinear
      depending on the nature of the forces involved. Simple "linear-free energy"
      relationships based on atomic properties have been well documented, for example,
      additivity for the interaction of small molecules with solvent, and, recently,
      have been explored for ligand-receptor interactions. Horton and Lewis propose
      such additivity based on buried surface area for protein-protein complexes. We
      investigated macromolecular interactions and found that the highest-affinity
      complexes do not fulfill this simple expectation. Instead, binding free energies
      of the tightest macromolecular complexes are roughly constant, independent of
      interface size, with the notable exception of DNA duplexes. By comparing these
      results to an earlier study of protein-ligand interactions we find that: (1) The
      maximum affinity is approximately 1.5 kcal/mol per nonhydrogen atom or 120
      cal/mol A(2) of buried surface area, comparable to results of our earlier work;
      (2) the lack of an increase in affinity with interface size is likely due to
      nonthermodynamic factors, such as functional and evolutionary constraints rather
      than some fundamental physical limitation. The implication of these results have
      some importance for molecular design because they suggest that: (1) The stability
      of any given complex can be increased significantly if desired; (2) small
      molecule inhibitors of macromolecular interactions are feasible; and (3)
      different functional classes of protein-protein complexes exhibit differences in
      maximal stability, perhaps in response to differing evolutionary pressures. These
      results are consistent with the widespread observation that proteins have not
      evolved to maximize thermodynamic stability, but are only marginally stable.

PMID- 12211033
TI  - Triage protein fold prediction.
AB  - We have constructed, in a completely automated fashion, a new structure template
      library for threading that represents 358 distinct SCOP folds where each model is
      mathematically represented as a Hidden Markov model (HMM). Because the large
      number of models in the library can potentially dilute the prediction measure, a
      new triage method for fold prediction is employed. In the first step of the
      triage method, the most probable structural class is predicted using a set of
      manually constructed, high-level, generalized structural HMMs that represent
      seven general protein structural classes: all-alpha, all-beta, alpha/beta,
      alpha+beta, irregular small metal-binding, transmembrane beta-barrel, and
      transmembrane alpha-helical. In the second step, only those fold models belonging
      to the determined structural class are selected for the final fold prediction.
      This triage method gave more predictions as well as more correct predictions
      compared with a simple prediction method that lacks the initial classification
      step. Two different schemes of assigning Bayesian model priors are presented and
      discussed.

PMID- 12211034
TI  - Progress toward virtual screening for drug side effects.
AB  - The development and application of a computational protocol for conducting
      virtual screens of drug side interactions is described. A conventional drug
      docking algorithm (AutoDock) is used to conduct two separate studies. First, a
      series of docking simulations is performed by using guanosine diphosphate and
      adenosine diphosphate as prototype drugs with the goal of successfully
      differentiating known receptors from a large number of bait receptors. Using the
      electrostatic energy of the purine ring as a basis for discrimination allows the
      correct identification of receptors in blind studies with 100% specificity and
      94% sensitivity. In a second study, similar methodology is used to investigate
      the binding of clinically relevant inhibitors (Gleevec, purvalanol A, and
      hymenialdisine) to a variety of protein kinase targets. Overall, excellent
      agreement between experimental and predicted preferences for kinase targets is
      obtained. An important conclusion from the latter study is that homology-modeled
      structures of putative receptors may reasonably be used as targets for docking
      when directly solved crystal structures are not available. The prospects for
      routine application of the methodology as a means of identifying potential side
      interactions of candidate drugs are discussed.

PMID- 12211035
TI  - Protein domain identification and improved sequence similarity searching using
      PSI-BLAST.
AB  - Protein sequences containing more than one structural domain are problematic when
      used in homology searches where they can either stop an iterative database search
      prematurely or cause an explosion of a search to common domains. We describe a
      method, DOMAINATION, that infers domains and their boundaries in a query sequence
      from local gapped alignments generated using PSI-BLAST. Through a new technique
      to recognize domain insertions and permutations, DOMAINATION submits delineated
      domains as successive database queries in further iterative steps. Assessed over
      a set of 452 multidomain proteins, the method predicts structural domain
      boundaries with an overall accuracy of 50% and improves finding distant
      homologies by 14% compared with PSI-BLAST. DOMAINATION is available as a web
      based tool at http://mathbio.nimr.mrc.ac.uk, and the source code is available
      from the authors upon request.

PMID- 12211036
TI  - Normal mode analysis of macromolecular motions in a database framework:
      developing mode concentration as a useful classifying statistic.
AB  - We investigated protein motions using normal modes within a database framework,
      determining on a large sample the degree to which normal modes anticipate the
      direction of the observed motion and were useful for motions classification. As a
      starting point for our analysis, we identified a large number of examples of
      protein flexibility from a comprehensive set of structural alignments of the
      proteins in the PDB. Each example consisted of a pair of proteins that were
      considerably different in structure given their sequence similarity. On each
      pair, we performed geometric comparisons and adiabatic-mapping interpolations in
      a high-throughput pipeline, arriving at a final list of 3,814 putative motions
      and standardized statistics for each. We then computed the normal modes of each
      motion in this list, determining the linear combination of modes that best
      approximated the direction of the observed motion. We integrated our new motions
      and normal mode calculations in the Macromolecular Motions Database, through a
      new ranking interface at http://molmovdb.org. Based on the normal mode
      calculations and the interpolations, we identified a new statistic, mode
      concentration, related to the mathematical concept of information content, which
      describes the degree to which the direction of the observed motion can be
      summarized by a few modes. Using this statistic, we were able to determine the
      fraction of the 3,814 motions where one could anticipate the direction of the
      actual motion from only a few modes. We also investigated mode concentration in
      comparison to related statistics on combinations of normal modes and correlated
      it with quantities characterizing protein flexibility (e.g., maximum backbone
      displacement or number of mobile atoms). Finally, we evaluated the ability of
      mode concentration to automatically classify motions into a variety of simple
      categories (e.g., whether or not they are "fragment-like"), in comparison to
      motion statistics. This involved the application of decision trees and feature
      selection (particular machine-learning techniques) to training and testing sets
      derived from merging the "list" of motions with manually classified ones.

PMID- 12211037
TI  - MIAX: a new paradigm for modeling biomacromolecular interactions and complex
      formation in condensed phases.
AB  - A new paradigm is proposed for modeling biomacromolecular interactions and
      complex formation in solution (protein-protein interactions so far in this
      report) that constitutes the scaffold of the automatic system MIAX (acronym for
      Macromolecular Interaction Assessment X). It combines in a rational way a series
      of computational methodologies, the goal being the prediction of the most native
      like protein complex that may be formed when two isolated (unbound) protein
      monomers interact in a liquid environment. The overall strategy consists of first
      inferring putative precomplex structures by identification of binding sites or
      epitopes on the proteins surfaces and a simultaneous rigid-body docking process
      using geometric instances alone. Precomplex configurations are defined here as
      all those decoys the interfaces of which comply substantially with the inferred
      binding sites and whose free energy values are lower. Retaining all those
      precomplex configurations with low energies leads to a reasonable number of
      decoys for which a flexible treatment is amenable. A novel algorithm is
      introduced here for automatically inferring binding sites in proteins given their
      3-D structure. The procedure combines an unsupervised learning algorithm based on
      the self-organizing map or Kohonen network with a 2-D Fourier spectral analysis.
      To model interaction, the potential function proposed here plays a central role
      in the system and is constituted by empirical terms expressing well-characterized
      factors influencing biomacromolecular interaction processes, essentially
      electrostatic, van der Waals, and hydrophobic. Each of these procedures is
      validated by comparing results with observed instances. Finally, the more
      demanding process of flexible docking is performed in MIAX embedding the
      potential function in a simulated annealing optimization procedure. Whereas
      search of the entire configuration hyperspace is a major factor precluding
      hitherto systems from efficiently modeling macromolecular interaction modes and
      complex structures, the paradigm presented here may constitute a step forward in
      the field because it is shown that a rational treatment of the information
      available from the 3-D structure of the interacting monomers combined with
      conveniently selected computational techniques can assist to elude search of
      regions of low probability in configuration space and indeed lead to a highly
      efficient system oriented to solve this intriguing and fundamental biologic
      problem.

PMID- 12211038
TI  - NMR structure of conserved eukaryotic protein ZK652.3 from C. elegans: a
      ubiquitin-like fold.

PMID- 12211040
TI  - Defining the boundaries of public health.

PMID- 12211039
TI  - Crystal structure of D-ribose-5-phosphate isomerase (RpiA) from Escherichia coli.

PMID- 12211041
TI  - Smallpox in Glasgow, 1900-1902.

PMID- 12211042
TI  - Alphavirus vectors and vaccination.
AB  - Alphaviruses are positive-stranded RNA viruses that have a broad host range and
      therefore are capable of replicating in many vertebrate and invertebrate cells.
      The single-stranded alphavirus genome is divided into two ORFs. The first ORF
      encodes the nonstructural proteins that are translated upon entry of the virus
      into the cytoplasm and are responsible for transcription and replication of viral
      RNA. The second ORF is under the control of a subgenomic promoter and normally
      encodes the structural proteins, which are responsible for encapsidation of viral
      RNA and final assembly into enveloped particles. Expression vectors have been
      engineered from at least three alphaviruses in which the structural protein gene
      region has been replaced by heterologous genes and have been shown to express
      high levels of the heterologous protein in cultured cells. These RNA vectors,
      known as replicons, are capable of replicating on their own but are not packaged
      into virus-like particles unless the structural proteins are provided in trans.
      Thus, replicons are single cycle vectors incapable of spreading from infected to
      noninfected cells. Because of these features, alphavirus replicon vectors are
      being developed as a platform vaccine technology for numerous viral, bacterial,
      protozoan and tumour antigens where they have been shown to be efficient inducers
      of both humoral and T cell responses. In addition, as the alphavirus structural
      proteins are not expressed in vaccine recipients, antivector immune responses are
      generally minimal, allowing for multiple effective immunisations of the same
      individual.

PMID- 12211043
TI  - DNA-based immunotherapy: potential for treatment of chronic viral hepatitis?
AB  - Persistent HBV and HCV infection represent major causes of chronic liver disease
      with a high risk of progression to liver cirrhosis and hepatocellular carcinoma
      (HCC). Conventional protein-based vaccines are highly efficacious in preventing
      HBV infection; whereas in therapeutic settings with chronically infected
      patients, results have been disappointing. Prophylactic vaccination against HCV
      infection has not yet been achieved due to many impediments including frequent
      spontaneous mutations of the virus with escape from immune system control. Using
      animal models it has been demonstrated that DNA-based immunisation strategies may
      overcome this problem because of their potential to induce immunity against
      multiple viral epitopes. DNA-based vaccines mimic the effect of live attenuated
      viral vaccines, eliciting cell mediated immunity in addition to inducing humoral
      responses. Efficacy may further be improved by addition of DNA encoding
      immunomodulatory cytokines and more recently, direct genetic modulation of
      antigen-presenting cells, such as dendritic cells (DC), has been shown to
      increase antigen-specific immune responses. This review focuses on immunological
      aspects of chronic HBV and HCV infection and on the potential of DNA- and DC
      based vaccines for the treatment of chronic viral hepatitis.

PMID- 12211044
TI  - The role of Epstein-Barr virus-encoded small RNAs (EBERs) in oncogenesis.
AB  - Epstein-Barr virus (EBV)-encoded RNAs (EBERs) are the most abundant viral
      transcripts in latently EBV-infected cells. Recently, we found that EBERs play a
      key role in the maintenance of malignant phenotypes of Burkitt's lymphoma (BL)
      cells. They confer clonability in soft agarose, tumorigenicity in immunodeficient
      mice, resistance to apoptosis and induction of interleukin (IL)-10, which acts as
      an autocrine growth factor of BL cells. Furthermore, we demonstrated that EBERs
      confer resistance to interferon (IFN)-alpha-induced apoptosis by inhibition of
      double-stranded (ds) RNA-activated protein kinase (PKR), which is the key
      mediator of the antiviral effect of IFN-alpha. These studies provide a new notion
      that RNA molecules contribute to oncogenesis.

PMID- 12211045
TI  - Varicella-zoster virus latency in human ganglia.
AB  - Varicella-zoster virus (VZV) is a human herpesvirus which causes varicella
      (chickenpox) as a primary infection, and, following a variable period during
      which it remains in latent form in trigeminal and dorsal root ganglia,
      reactivates in later life to cause herpes zoster (shingles). VZV is a significant
      cause of neurological disease including post-herpetic neuralgia which may be
      persistent and highly resistant to treatment, and small and large vessel
      encephalitis. VZV infections are more frequent with advancing age and in
      immunocompromised individuals. An understanding of the mechanisms of latency is
      crucial in developing effective therapies for VZV infections of the nervous
      system. Such studies have been hampered by the difficulties in working with the
      virus and also the lack of a good animal model of VZV latency. It is known that
      the ganglionic VZV burden during latency is low. Two of the key questions that
      have been addressed are the cellular site of latent VZV and the identity of the
      viral genes which are transcribed during latency. There is now a consensus that
      latent VZV resides predominantly in ganglionic neurons with less frequent
      infection of non-neuronal satellite cells. There is considerable evidence to show
      that at least five viral genes are transcribed during latency. Unlike herpes
      simplex virus-1 latency, viral protein expression has been demonstrated during
      VZV latency. A precise knowledge of which viral genes are expressed is crucial in
      devising novel antiviral therapy using expressed genes as therapeutic targets.
      Whether gene expression at both the transcriptional and translational levels is
      more extensive than currently reported will require much more work and probably
      new molecular technology.

PMID- 12211046
TI  - Malignant tumors of the nasal cavity and paranasal sinuses.
AB  - PURPOSE: To evaluate the role of radiation therapy in patients with nasal cavity
      and paranasal sinus tumors. MATERIALS AND METHODS: Between October 1964 and July
      1998, 78 patients with malignant tumors of the nasal cavity (48 patients),
      ethmoid sinus (24 patients), sphenoid sinus (5 patients), or frontal sinus (1
      patient) were treated with curative intent by radiation therapy alone or in the
      adjuvant setting. There were 25 squamous cell carcinomas, 14 undifferentiated
      carcinomas, 31 minor salivary gland tumors (adenocarcinoma, adenoid cystic
      carcinoma, and mucoepidermoid carcinoma), 8 esthesioneuroblastomas, and 1
      transitional cell carcinoma. Forty-seven patients were treated with irradiation
      alone, 25 with surgery and postoperative irradiation, 2 with preoperative
      irradiation and surgery, and 4 with chemotherapy in combination with irradiation
      with or without surgery. RESULTS: The 5-year actuarial local control rate for
      stage I (limited to the site of origin; 22 patients) was 86%; for stage II
      (extension to adjacent sites (eg, adjacent sinuses, orbit, pterygomaxillary
      fossa, nasopharynx; 21 patients) was 65%; and for stage III (destruction of skull
      base or pterygoid plates, or intracranial extension; 35 patients) was 34%. The 5
      year actuarial local control rate for patients receiving postoperative
      irradiation was 79% and for patients receiving irradiation alone was 49% (p
      =.05). The 5-, 10-, 15-, and 20-year ultimate local control rates for all 78
      patients were 60%, 56%, 48%, and 48%, respectively. The 5-, 10-, 15-, and 20-year
      cause-specific survival rates for all 78 patients were 56%, 45%, 39%, and 39%,
      respectively. The 5-, 10-, 15-, and 20-year absolute survival rates for all 78
      patients were 50%, 31%, 21%, and 16%, respectively. Of the 67 (86%) patients who
      were initially seen with node-negative disease, 39 (58%) received no elective
      neck treatment, and 28 (42%) received elective neck irradiation. Of the 39
      patients who received no elective neck treatment, 33 (85%) did not experience
      recurrence in the neck compared with 25 (89%) of 28 patients who received
      elective neck irradiation. Most patients who received elective neck irradiation
      (57%) had stage III disease. Twenty-one (27%) of 78 patients had unilateral
      blindness develop secondary to radiation retinopathy or optic neuropathy; the
      complication was anticipated in most of these patients, because the ipsilateral
      eye was irradiated to a high dose. Four patients (5%) unexpectedly had bilateral
      blindness develop because of optic neuropathy. All four of these patients
      received irradiation alone. CONCLUSION: Surgery and postoperative radiation
      therapy may result in improved local control, absolute survival, and
      complications when compared with radiation therapy alone. Elective neck
      irradiation is probably unnecessary for patients with early-stage disease.

PMID- 12211047
TI  - Nutrition and pharyngeal cancer: results from a case-control study in Spain.
AB  - BACKGROUND: Oropharyngeal and hypopharyngeal cancer is increasing all over the
      world, frequently affecting more and more women and younger individuals and not
      only the typical 50- to 60-year-old heavy smoker and drinking man. In addition, 5
      year overall survival rate remains poor (30% to 40% in most series), despite
      advances in treatment. Therefore, it is crucial to understand as accurately as
      possible the risk factors for these malignancies to improve primary prevention.
      METHODS: We report the results from a case-control study of pharyngeal cancer
      risk factors conducted in Spain involving 232 consecutive patients who were
      gender- and age-matched with 232 controls. Data were collected by interviewer
      administered personal interview. RESULTS: Our results show that low intake of
      fruit, fruit juice, uncooked vegetables, dietary fiber-containing foods (legume
      and cereals), fish, milk, and dairy products is an independent risk factor for
      pharyngeal cancer and that high consumption of meat and fried foods also
      increases the risk once data are adjusted for tobacco smoking and alcohol
      drinking. CONCLUSIONS: Although findings for fruit, juice, and uncooked
      vegetables are in accordance with those from other authors and can be explained
      on a biologic basis, the relationship between pharyngeal cancer and dietary
      excess of saturated fatty acids needs experimental investigation. Findings for
      milk, dairy products, and fish also warrant more detailed epidemiologic research
      because of conflicting data reported in the literature and because of the
      reportedly ambiguous role of retinol in human cancers. No conclusive explanations
      for the protective effect of dietary fiber-containing foods can be put forward
      today. Our results are uniquely attributable to oropharyngeal and hypopharyngeal
      cancers because of the small size of our nasopharyngeal cancer subsample.

PMID- 12211048
TI  - Human papillomavirus and p53 mutational status as prognostic factors in head and
      neck carcinoma.
AB  - BACKGROUND: Mutations of the p53 tumor-suppressor gene are common in squamous
      cell carcinoma of the head and neck (SCCHN) and may portend a worse prognosis.
      Human papillomavirus (HPV) represents another potential prognostic factor for
      SCCHN. The oncogenic potential of HPV may be due to the ability of its E6
      oncoprotein to promote degradation of wild-type p53 protein. We wish to determine
      whether there is a lower incidence of p53 mutations in HPV-positive versus HPV
      negative tumors, and if HPV and/or p53 status has an impact on survival. METHODS:
      Thirty-two SCCHN specimens were analyzed for mutations of the p53 gene using
      single-strand conformational polymorphism (SSCP) analysis followed by DNA
      sequencing. The HPV status of all specimens was evaluated by use of polymerase
      chain reaction with HPV consensus primers and Southern blot hybridization.
      Pertinent clinical information was obtained from chart review. RESULTS: Nonsilent
      p53 mutations were present in 2 of 15 (13%) of HPV-positive tumors compared with
      6 of 17 (35%) of HPV-negative tumors (p =.229; Fisher's exact test, odds
      ratio.28). A survival advantage was found between HPV-positive compared with HPV
      negative specimens (p =.0264) and between p53 wild type compared with p53 mutant
      specimens (p =.01) by univariate log rank analysis. When stratified according to
      both HPV and p53 status, a statistically significant survival difference was
      observed largely because of a 100% survival for the HPV-positive/p53 wild-type
      group (p =.003). CONCLUSIONS: This preliminary study supports the notion that the
      presence of HPV confers a survival advantage among HNSCC patients, particularly
      when p53 is wild type.

PMID- 12211049
TI  - Clinical significance of interleukin-6 and interleukin-6 receptor expressions in
      oral squamous cell carcinoma.
AB  - BACKGROUND: Recent studies showed that interleukin-6 (IL-6) played a role in
      tumor development. However, available information about the prognostic
      significance of IL-6 and IL-6 receptors (IL-6R) for oral squamous cell carcinoma
      (OSCC) is limited. METHODS: Eighty-six patients with OSCC were enrolled.
      Immunohistochemical staining was used to determine IL-6R expression and in-situ
      hybridization for IL-6 mRNA transcripts in surgical specimens. Clinicopathologic
      correlation was evaluated by chi-square test and survival by log rank test.
      RESULTS: Expression rates of IL-6R and IL-6 mRNA transcripts in tumor specimens
      were 73.3% and 54.7%, much higher than those in nontumor mucosa (p <.001). IL-6R
      overexpression was associated with larger tumors and more advanced histologic
      grade (p <.05). The presence of IL-6 mRNA transcripts was inversely correlated
      with distant metastasis, lymph node involvement, and second primary SCC (p <.05)
      and predicted better survival (p =.007). CONCLUSIONS: IL-6-IL-6R coexpression was
      rather high in OSCC, and IL-6 mRNA transcript expression might influence patient
      survival. The biologic role of IL-6-IL-6R coexpression in OSCC needs additional
      investigation.

PMID- 12211050
TI  - The pattern of expression of Mn and Cu-Zn superoxide dismutase varies among
      squamous cell cancers of the lung, larynx, and oral cavity.
AB  - BACKGROUND: Despite the importance of reactive oxygen species (ROS) in the
      development of smoking-related cancers, little is known about the pattern of
      expression of ROS scavengers in these cancers. METHODS: In this present study, we
      examined the expression of manganese superoxide dismutase (Mn-SOD) and
      copper/zinc superoxide dismutase (Cu-Zn-SOD), which are essential enzymes that
      eliminate ROS, in squamous cell cancers (SCCs) of the lung (n = 12), larynx (n =
      13), and oral cavity (n = 20). RESULTS: SCCs of larynx and oral cavity showed
      significantly enhanced immuhistochemical expression of Mn-SOD compared with the
      matched uninvolved epithelium. The higher expression of Mn-SOD was shown to be
      late and early events in the process of SCC development in the larynx and the
      oral cavity, respectively. The expression of Mn-SOD in SCCs of the lung was
      significantly lower compared with luminal cells of the uninvolved epithelium but
      not compared with basal cells or an average expression of SOD in basal and
      luminal cells. The expression of both Mn-SOD and cytoplasmic or nuclear Cu-Zn-SOD
      in bronchial epithelium adjacent to invasive cancer was significantly lower
      compared with its expression in the uninvolved bronchial epithelium away from
      cancer. This resulted in a significant difference in SOD expression between
      cancer and uninvolved bronchial epithelium away from cancer but not between
      cancer and uninvolved epithelium adjacent to cancer. CONCLUSIONS: There are
      significant differences in the expression of Mn-SOD and Cu-Zn-SOD among SCCs of
      the lung, larynx, and oral cavity. The results also suggest that variations in
      distance between cancer and uninvolved tissues evaluated could contribute to
      conflicting results of SOD expression.

PMID- 12211051
TI  - Reliable detection of p53 aberrations in squamous cell carcinomas of the head and
      neck requires transcript analysis of the entire coding region.
AB  - BACKGROUND: Aberrations of the p53 tumor suppressor gene are common events in
      squamous cell carcinomas of the head and neck (SCCHN). However, reported
      frequencies range considerably, and the predictive value of aberrant p53 is
      continuing to be an issue of controversy. These inconsistencies are possibly
      caused by methodical limitations. METHODS: In cell lines established from 23
      SCCHN, we performed sequence analysis of p53 mRNA and genomic DNA, as well as
      protein detection using immunohistochemistry and Western blotting. RESULTS: Of
      the 23 SCCHN, 21 (91%) tumors have aberrant or no p53, including four aberrations
      (19%) located outside the usually examined exons 5 to 9. A second allele is
      present in 11, and the respective transcript in 4 tumors. Expression of protein
      could be detected in only 12 of the 21 p53 aberrant tumors (57%). CONCLUSIONS:
      Depending on the methodical approach applied, a considerable number of SCCHN may
      be misclassified regarding their p53 status.

PMID- 12211052
TI  - Molecular cytogenetic analysis of head and neck squamous cell carcinoma: By
      comparative genomic hybridization, spectral karyotyping, and expression array
      analysis.
AB  - BACKGROUND: A combination of molecular cytogenetic and expression array analysis
      has been performed on head and neck squamous cell carcinoma (HNSCC) of the oral
      cavity and supraglottis. These studies were performed to identify consensus
      regions of chromosomal imbalance and structural rearrangement to determine
      whether genes located in these genomic regions are subject to alterations in gene
      expression. Such combinatorial studies may help to identify recurrent patterns of
      altered gene expression in the context of specific chromosomal changes. METHODS:
      Comparative genomic hybridization (CGH) was used to identify net genomic
      imbalances and spectral karyotyping (SKY) to visualize the numerical and
      structural chromosomal changes in metaphase preparations. Expression microarray
      analysis of HNSCC cell lines and primary tongue tumors was also performed to
      identify genes that were commonly overexpressed or underexpressed compared with
      adjacent normal tissue. RESULTS: CGH detected gains at 3q (64%), 8q (45%) and
      6q22-qter (45%) and losses at 18q22-qter (27%). SKY analysis of seven cell lines
      identified frequent structural rearrangement of the following chromosomal
      regions: 3q, 5p13-q11.2, 5q32-q34, 7p12-q11.2, 8p12-q12, 9p, 10p, 13p13-q12,
      14q11.1-q11.2, 15p13-q11.2, 16p11.1-q11.1, 18q22-q23, and 22p13-q11.2. Consistent
      deregulation of interleukin 8, integrin alpha-6, c-MYC, epithelial discoidin
      domain receptor 1, and sterol regulatory element binding protein were apparent by
      expression analysis. Interestingly, some of these genes map to regions of genomic
      imbalance and chromosomal rearrangement as determined by our molecular
      cytogenetic analysis. CONCLUSIONS: In this small study, a combinatorial analysis
      using SKY, CGH, and microarray provides a model linking the changes in gene
      expression to changes in chromosomal dosage and structure. This approach has
      identified a subset of genetic changes that provide new opportunities for
      investigating the genetic basis of tumorigenesis in HNSCC.

PMID- 12211053
TI  - Spindle epithelial tumor with thymus-like differentiation (SETTLE) of the
      thyroid.
AB  - BACKGROUND: Tumors of the so-called intrathyroidal epithelial thymoma type are a
      rare group of thyroid neoplasm tumors. Of this type of tumor, spindle epithelial
      tumor with thymus like differentiation (SETTLE) has been reported only 17 times
      in English literature. METHODS: An 18-year-old woman was initially seen with a 6
      cm left thyroid mass that was resected with a left thyroidectomy. Histopathologic
      features of the excised left thyroid tumor together with an immunohistochemistry
      and electron microscopy led us to a diagnosis of SETTLE. RESULTS: Most of the
      specimen was composed of highly cellular spindle cells that formed intersecting
      and streaming fascicles. The spindle cells showed both vimentin immunoreactivity
      and cytokeratin immunoreactivity but no immunoreactivity for thyroglobulin or
      calcitonin. Electron microscopic examination of the spindle cells demonstrated
      prominent cytoplasmic tonofilaments, desmosomes, and basal lamina consistent with
      epithelial cell origin. DNA content analysis by flow cytometry revealed DNA
      diploidy. CONCLUSIONS: SETTLE of thyroid gland is an extremely rare entity. A
      review of the literature reveals that SETTLE has distinctive morphologic features
      and an immunohistochemical profile.

PMID- 12211054
TI  - Intramanchette transport (IMT): managing the making of the spermatid head,
      centrosome, and tail.
AB  - Intramanchette transport (IMT) and intraflagellar transport (IFT) share similar
      molecular components: a raft protein complex transporting cargo proteins
      mobilized along microtubules by molecular motors. IFT, initially discovered in
      flagella of Chlamydomonas, has been also observed in cilia of the worm
      Caenorhabditis elegans and in mouse ciliated and flagellated cells. IFT has been
      defined as the mechanism by which protein raft components (also called IFT
      particles) are displaced between the flagellum and the plasma membrane in the
      anterograde direction by kinesin-II and in the retrograde direction by
      cytoplasmic dynein 1b. Mutation of the gene Tg737, encoding one of the components
      of the raft protein complex, designated Polaris in the mouse and IFT88 in both
      Chlamydomonas and mouse, results in defective ciliogenesis and flagellar
      development as well as asymmetry in left-right axis determination. Polaris/IFT88
      is detected in the manchette of mouse and rat spermatids. Indications of an IMT
      mechanism originated from the finding that two proteins associated with the
      manchette (Sak57/K5 and TBP-1, the latter a component of the 26S proteasome)
      repositioned to the centrosome and sperm tail once the manchette disassembled.
      IMT has the features of the IFT machinery but, in addition, facilitates
      nucleocytoplasmic exchange activities during spermiogenesis. An example is Ran, a
      small GTPase present in the nucleus and cytoplasm of round spermatids and in the
      manchette of elongating spermatids. Upon disassembly of the manchette, Ran GTPase
      is found in the centrosome region of elongating spermatids. Because defective
      molecular motors and raft proteins result in defective flagella, cilia, and cilia
      containing photoreceptor cells in the retina, IMT and IFT are emerging as
      essential mechanisms for managing critical aspects of sperm development. Details
      of specific role of Ran GTPase in nucleocytoplasmic transport and its relocation
      from the manchette to the centrosome to the sperm tail await elucidation.

PMID- 12211055
TI  - Sox9 in a teleost fish, medaka (Oryzias latipes): evidence for diversified
      function of Sox9 in gonad differentiation.
AB  - Sox9 is a transcription factor containing the Sry-related high-mobility-group
      (HMG) box. Mutations in human SOX9 gene cause skeletal defects and male-to-female
      sex reversal, indicating its essential roles in chondrogenesis and testis
      development. Comparative studies have shown that Sox9 is expressed in
      chondrogenic tissues and testis in other vertebrates. Therefore, it was suggested
      that roles of Sox9 in cartilage and male gonad development are conserved among
      vertebrates. To investigate the evolutional significance of Sox9 in the gonad and
      cartilage development of teleost fish, we isolated medaka sox9 and analyzed its
      expression. Two kinds of transcripts (sox9 and sox9lf) were isolated by cDNA
      library screening. The sox9 encoded 487 amino acids and showed approximately 70%
      amino acid identity with known vertebrate SOX9 proteins. The sox9lf was a longer
      form of the sox9, which was transcribed from an additional exon in the 5'
      upstream region. Interestingly, the expression of medaka sox9 was predominantly
      observed in the adult ovary by northern blot and in situ hybridization analyses,
      whereas in the testis, its expression was detectable only by RT-PCR. During
      medaka embryogenesis, its expression was observed in the cranial cartilage and
      pectoral fin endoskeleton. These observations suggest that the function of Sox9
      in the cartilage is conserved among vertebrates, while that in the gonad is quite
      different in medaka.

PMID- 12211056
TI  - Toxicogenomic effects of neonatal exposure to diethylstilbestrol on mouse
      testicular gene expression in the long term: a study using cDNA microarray
      analysis.
AB  - We examined the effect of neonatal exposure to diethylstilbestrol (DES) on mouse
      testicular gene expression, using in-house mouse fetus (day 14.5) cDNA
      microarrays. Newborn male ICR mice were exposed to DES (50 microg/mouse/day) from
      neonatal day 1 to 5. Differential expression was detected in 14 genes in 4-week
      old (day 28) mouse testes by cDNA microarray analysis; 11 genes (AI035263,
      AU080565, AU080361, AU080678, AI131681, AU080631, AA986882, AI037066, AA986537,
      AI156816, and AI596237) were up-regulated and three genes (AI131656, AI118968,
      and AI117606) were down-regulated in DES-treated mouse testes. Higher expression
      levels of the former eight genes, out of the up-regulated genes picked-up by the
      microarray, were also confirmed by reverse transcription and real-time polymerase
      chain reaction (real-time RT-PCR) analysis. However, the differential expression
      of other genes could not be confirmed. Real-time RT-PCR analysis also revealed
      that expression levels of the eight genes were still higher in DES-treated testes
      at 8 and 12 weeks of age. Our results suggest that cDNA microarray analysis is a
      useful method by which a large number of gene expressions are simultaneously
      detected and changes in gene expression are screened. In addition, our results
      suggest that these genes, whose expressions are changed in the testes of adult
      mice by fetal or neonatal exposure to exogenous chemicals, might be candidates
      for predictive biological markers.

PMID- 12211057
TI  - Structure and expression of the follicle-stimulating hormone receptor gene in a
      marsupial, Macropus eugenii.
AB  - Follicle stimulating hormone (FSH) is essential for folliculogenesis. The
      function of FSH is mediated through its receptor (FSHr) and modulation of the
      receptor is thought to be the mechanism by which the responsiveness of follicles
      to gonadotrophins is regulated. FSHr is alternatively spliced to produce several
      transcripts in all eutherian species studied. However, controversy exists over
      the significance of alternatively spliced transcripts. In this study, we cloned
      and characterised the tammar wallaby (Macropus eugenii) FSHr gene and examined
      its expression. Comparison of gene structure and function between marsupials and
      eutherians enables identification of conserved features that are likely to be of
      functional significance. Tammar FSHr shares 94% amino acid similarity with human
      FSHr and is expressed in both the adult testis and ovary suggesting a similar
      function for this gene in both marsupials and eutherians. Tammar FSHr undergoes
      alternate splicing to produce four transcripts consistent with the splice
      variants seen in eutherians. These results strongly suggest that alternate
      splicing is of functional significance in the ovary since it has remained a
      highly conserved character of this gene for over 100 million years of divergent
      evolution.

PMID- 12211058
TI  - Inheritance of resistance of bovine preimplantation embryos to heat shock:
      relative importance of the maternal versus paternal contribution.
AB  - Brahman preimplantation embryos are less affected by exposure to heat shock than
      Holstein embryos. Two experiments were conducted to test whether the ability of
      Brahman embryos to resist the deleterious effects of heat shock was a result of
      the genetic and cellular contributions from the oocyte, spermatozoa, or a
      combination of both. In the first experiment, Brahman and Holstein oocytes were
      collected from slaughterhouse ovaries and fertilized with spermatozoa from an
      Angus bull. A different bull was used for each replicate to eliminate bull
      effects. On day 4 after fertilization, embryos >or= 9 cells were collected and
      randomly assigned to control (38.5 degrees C) or heat shock (41 degrees C for 6
      hr) treatments. The proportion of embryos developing to the blastocyst (BL) and
      advanced blastocyst (ABL; expanded and hatched) stages was recorded on day 8.
      Heat shock reduced the number of embryos produced from Holstein oocytes that
      developed to BL (P < 0.001, 55.6 +/- 4.2% vs. 29.8 +/- 4.2%) and ABL (P < 0.01,
      37.7 +/- 3.6% vs. 12.2 +/- 3.6%) on day 8 as compared to controls. In contrast,
      heat shock did not reduce development of embryos produced from Brahman oocytes
      (BL = 42.1 +/- 4.8% vs. 55.6 +/- 4.8% for 38.5 and 41 degrees C, respectively;
      ABL = 17.6 +/- 4.2% vs. 32.4 +/- 4.2%). In the second experiment, oocytes from
      Holstein cows were fertilized with semen from bulls of either Brahman or Angus
      breeds. Heat shock of embryos >or= 9 cells reduced development to BL (P < 0.002)
      and ABL (P < 0.005) for embryos sired by both Brahman (BL = 54.3 +/- 7.7% vs.
      23.4 +/- 7.7%; ABL = 43. +/- 7.4% vs. 7.9 +/- 7.4%, for 38.5 and 41 degrees C,
      respectively) and Angus bulls (BL = 57.9 +/- 7.7% vs. 31.0 +/- 7.7%; ABL = 33.6
      +/- 7.4% vs. 18.4 +/- 7.4%, for 38.5 and 41 degrees C, respectively). There were
      no breed x temperature interactions. Results suggest that the oocyte plays a more
      significant role in the resistance of Brahman embryos to the deleterious effects
      of heat shock than the spermatozoa.

PMID- 12211059
TI  - Predictive variables of in vitro fertilization and pre-implantation embryo
      development in the mouse.
AB  - The present study aims to analyze the cause-effect relationships among several in
      vitro fertilization and pre-implantation embryo development variables in the
      mouse. Superovulation of hybrid (C57Bl/6JIco female X CBA/JIco male) female mice
      of 4-6 weeks of age was induced by a priming injection of pregnant mare's serum
      gonadotropin at the estrus stage of the estrous cycle followed after a 48-hr
      interval by human chrorionic gonadotropin. Ovulated cumulus-enclosed oocytes were
      inseminated with sperm from hybrid males of 12-16 weeks of age. The multiple
      linear regression analyses performed indicated that (a) total number of ovulated
      oocytes is a good predictor of both fertilization frequency and total number of
      cells in day-5 blastocysts; (b) fertilization frequency predicts percentage of
      day-5 blastocysts; (c) total number of cells in day-5 blastocysts is predicted by
      percentage of day-5 blastocysts; and (d) total number of cells in day-5
      blastocysts predicts percentage of apoptotic cells, number of inner cell mass
      (ICM) and trophectoderm (TE) cells, and ICM/TE ratio in day-5 blastocysts.
      Mitotic index in day-5 blastocysts was positively correlated with total number of
      ovulated oocytes, percentage of ovulated cumulus-enclosed oocytes, fertilization
      frequency, percentage of day-5 blastocysts and total number of cells in day-5
      blastocysts. On the contrary, it was negatively correlated with percentage of
      apoptotic cells in day-5 blastocysts.

PMID- 12211060
TI  - Basigin expression and hormonal regulation in mouse uterus during the peri
      implantation period.
AB  - Basigin, a transmembrane glycoprotein belonging to the immunoglobulin
      superfamily, has been shown to be essential for fertilization and implantation.
      The aim of this study was to determine the expression and hormonal regulation of
      basigin gene in mouse uterus during the peri-implantation period. Basigin
      immunostaining and mRNA were strongly localized in luminal and glandular
      epithelium on day 1 of pregnancy and gradually decreased to a basal level from
      day 2-4 of pregnancy. Basigin mRNA expression in the sub-luminal stroma was first
      detected on day 3 of pregnancy and increased on day 4 of pregnancy. On day 5 of
      pregnancy, the expression of basigin protein and mRNA was only detected in the
      implanting embryos, and the luminal epithelium and sub-luminal stroma surrounding
      the embryos. A similar expression pattern of basigin was also induced in the
      delayed-implantation uterus which was activated by estrogen injection. On day 6-8
      of pregnancy, although a basal level of basigin protein was detected in the
      secondary decidual zone, basigin mRNA expression was strongly seen in this
      location. Basigin mRNA was also highly expressed in the decidualized cells under
      artificial decidualization. Estrogen significantly stimulated basigin expression
      in the ovariectomized mouse uterus. A high level of basigin immunostaining and
      mRNA was also seen in proestrus and estrus uteri. These results suggest that
      basigin expression is closely related to mouse implantation and up-regulated by
      estrogen.

PMID- 12211061
TI  - Immunological evidence for progesterone and estradiol receptors in the freshwater
      crayfish Austropotamobius pallipes.
AB  - In this article, we present evidence for progesterone and estradiol receptors (PR
      and ER, respectively) in the female of the crayfish Austropotamobius pallipes. To
      our knowledge, this is the first report of sex steroid receptors in crustaceans.
      By using immunohistochemistry and Western blotting approaches and employing three
      different antibodies against PR (human PR, chicken PR-hinge region, and chicken
      PR A/B domain) and antibodies against human ER, we showed the presence of PR in
      the ovary and hepatopancreas and ER in the hepatopancreas of the freshwater
      crayfish A. pallipes. The immunological characteristics and the tissue
      localization suggest a relatedness with both PR and ER in vertebrates along with
      their involvement in the modulation of reproductive functions in this
      crustaceans.

PMID- 12211062
TI  - Effects of the aromatase inhibitor fadrozole on plasma sex steroid secretion,
      spermatogenesis and epididymis morphology in the lizard, Podarcis sicula.
AB  - Recently, increasing importance has been attached to the role of estrogens and
      their receptors in male reproduction, since they have been found to be abundant
      in the male reproductive tract. In the lizard, Podarcis sicula, a seasonal
      breeder, estrogens seem to be involved in the regulation of testicular activity.
      Particularly, it has been hypothesized that the block of spermatogenesis and the
      complete regression of the epididymis and other secondary sexual characters
      (SSCs) in autumn might be due to high estrogen levels. To investigate the role of
      estrogens in the reproductive process of male lizards, we utilized Fadrozole
      ((AI) [4-(5,6,7,8-tetrahydroimidazole [1,5-a] pyridin-5-yl)-benzonitrile
      monohydrochloride] (CGS 16949A)), a nonsteroidal inhibitor of aromatase, the
      enzyme involved in the aromatization of androgens to estrogens, evaluating its
      effects on plasma sex-hormone release, spermatogenesis and epididymis morphology.
      For this purpose, adult male lizards, captured during the autumnal recrudescence,
      were intraperitoneally injected with 0.5 microg and 5 microg/g/body weight of AI
      for 15 and 30 days. In the animals treated with the higher AI dose, estrogen
      levels decreased if compared to the control groups, whereas androgen levels
      increased. Furthermore, histologic sections of testes and epididymes showed that
      the 30-day treatment with AI-induced spermatogenesis resumption with release of
      sperms into the large lumen of the seminiferous tubules, and the epididymes
      appeared more developed with moderately secreting columnar canal cells.
      Therefore, it is proposed that failure of spermatogenesis in autumn might be due
      to high estrogen levels.

PMID- 12211063
TI  - Involvement of endothelin-1 and its receptors in PGF2alpha-induced luteolysis in
      the rat.
AB  - The possible mediatory role of endothelin-1 (ET-1) in prostaglandin F(2alpha)
      (PGF(2alpha))-induced luteolysis in the rat was examined. The effect of
      PGF(2alpha) was tested on day 9 of pregnancy either in vivo, by injecting
      cloprostenol, an analog of PGF(2alpha) or in vitro, in isolated intact corpora
      lutea incubated with PGF(2alpha). Luteolysis was confirmed by progesterone
      determination in the peripheral blood serum or in the culture medium,
      respectively. Administration of cloprostenol (.0025 mg/rat) induced within 1 hr,
      a significant fall (from 56.8 to 27.6 ng/ml, P < 0.0001) in serum progesterone
      concentrations that was associated with an increased expression of the mRNA to ET
      1 and its protein product in rat luteal tissue. Elevated level of ET-1 were also
      determined at the spontaneous regression of the CL, upon parturition. Expression
      of the ET receptors, ETA and ETB was not affected by cloprostenol. On the other
      hand, this PGF(2alpha) analog induced expression of luteal VEGF mRNA. In vitro
      experiments demonstrate that the LH (100 ng/ml)-induced increase in luteal
      progesterone secretion was reduced by PGF(2alpha) (1 microg/ml). The inhibitory
      effect of PGF(2alpha) was reversed by BQ123 (10(- 7) M), that is a selective ETA
      receptor antagonist. We conclude that the PGF(2alpha)-induced elevation in luteal
      expression of ET-1 combined with the reversal of its luteolytic effect by an ETA
      receptor antagonist suggest that ET-1 may take part in the PGF(2alpha)-induced
      luteolysis in the rat.

PMID- 12211064
TI  - Ultrastructure of oocyte maturation, fertilization, and early embryo development
      in vitro in the Siberian tiger (Panthera tigris altaica).
AB  - The application of assisted reproduction techniques to wild cats has been stalled
      by a lack of basic knowledge of the reproductive biology in these species. In
      this study, the ultrastructure of Siberian tiger (Panthera tigris altaica)
      cumulus-oocyte-complexes (COCs), as well as in vitro produced (IVP) zygotes and
      embryos were investigated, to estimate the normality of the manipulated
      reproduction processes. Adult female tigers were subjected to a purified porcine
      pFSH/pLH stimulation treatment followed by oocyte aspiration. According to
      morphological appearance at the stereomicroscopical level, COCs were classified
      as mature, immature, or degenerated, and then allocated into the following
      groups: presumptively immature COCs, which were in vitro matured (IVM-group)
      before fixation; presumptively mature COCs, which were either fixed after
      retrieval (pre-IVF-group), following in vitro insemination (IVF-group) or
      following in vitro insemination and subsequent in vitro culture (IVC-group). All
      specimens were processed for light and transmission electron microscopy (TEM).
      Both the IVM- and pre-IVF-group included oocytes in meiotic stages ranging from
      prophase I to metaphase II, and some prophase I oocytes in the IVM-group were
      apparently in their growth phase. The IVF-group presented features of presumptive
      normal fertilization, but aberrations such as polynucleation were also noted. The
      IVC-group included cleavage stage embryos of which, however, many were
      polynucleated. In conclusion, the procedures used for stimulation, aspiration,
      and classification of COCs resulted in retrieval of a heterogeneous population of
      oocytes which, following IVF and IVC, displayed a high rate of developmental
      deviations.

PMID- 12211065
TI  - Centrosome dynamics and inheritance in related sexual and parthenogenetic
      Bacillus (Insecta Phasmatodea).
AB  - In animals, some general features of centrosome dynamics and inheritance have
      been widely recognized. The most acknowledged model assigns to sperm the
      contribution of a centriole to the fertilized egg, which in turn provides the
      pericentriolar materials, including gamma-tubulin, recruiting them from the
      cytoplasm: the main zygote microtubule organizing center (MTOC) is thus
      reconstituted to organize first the spermaster and then the full first embryonic
      spindle. Obviously the model cannot apply to parthenogenetic systems, which
      actually rely on egg components alone. In stick insects of the Bacillus genus,
      the spindle of both somatic and germ cells is clearly anastral, therefore we have
      been investigating their centrosome in sexual and parthenogenetic taxa by
      analyzing its component dynamics and transmission through the use of monoclonal
      beta- and gamma-tubulin antibodies and transmission electron microscopy (TEM). It
      has been shown that in sexually reproducing species the spermatozoon does not
      contribute the centriole, so that the egg wholly provides the MTOC and the
      ensuing anastral spindle of the embryo: MTs appear to derive from pronuclear
      chromatin surroundings and no asters are observed. The parthenogenetic embryo
      development is the same as the sexual one if syngamy is excepted. The
      parthenogenetic mechanism realized by these panoistic insects appears to differ
      from that observed in the meroistic hymenopteran and drosophilid species, where
      the embryo spindle derives from asters formed in the egg cortex. In stick
      insects, the lack of sperm contribution to embryonic centrosome appears to be a
      major trait accounting for the widespread occurrence of facultative and obligate
      parthenogenesis within the order.

PMID- 12211066
TI  - GPX5 is present in the mouse caput and cauda epididymidis lumen at three
      different locations.
AB  - In mice, GPX5 is a secreted protein abundantly synthesized by the caput
      epididymidis. The protein is secreted as early as the initial segment of the
      caput and is found subsequently associated with the sperm plasma membrane in a
      sub-acrosomic localization. We show here that GPX5 is present in the caput and
      cauda epididymides lumens in three different locations: either free as a soluble
      protein in the caput epididymal fluid, weakly bound to caput sperm membranes, or,
      finally, associated to lipid-containing structures conferring to the protein a
      protective effect against proteolytic digestions. Within the cauda epididymidis,
      the amount of free GPX5 is low compared to the caput and the association with
      sperm membranes proved to be more solid. In both caput and cauda sperm samples,
      the association of GPX5 with the sperm membrane protects GPX5 from proteolytic
      cleavages. Protection against proteolytic digestions can be overcome by physical
      treatments of epididymal fluid and sperm samples such as ultrasounds or very
      acidic pH. These data suggest that complex phenomena and structures participate
      in the transfer and binding of the caput-secreted GPX5 protein to the sperm
      plasma membrane.

PMID- 12211067
TI  - G(alpha)s levels regulate Xenopus laevis oocyte maturation.
AB  - Progesterone, produced by follicular cells, induces Xenopus laevis oocyte
      maturation through a very early event that inhibits the activity of the adenylyl
      cyclase effector system. The participation of a G-protein has been implicated,
      based on the fact that the inhibitory effect of the steroid is GTP-dependent, and
      it has been proposed that progesterone acts interfering with G(alpha)s function
      at the plasma membrane. Here we investigate whether the change in oocyte
      G(alpha)s levels affects the maturation process induced by progesterone.
      Overexpression of X. laevis wild type (wt) G(alpha)s and the constitutive
      activated G(alpha)s(QL) mutant, both blocked progesterone-induced maturation,
      G(alpha)s(QL) being much more effective than the wt protein. On the other hand,
      depletion of G(alpha)s, by the use of antisense oligonucleotides, caused
      spontaneous maturation measured as MAPK activation, indicating clearly that the
      presence of G(alpha)s is necessary to keep oocytes arrested. Overexpression of
      three different G-protein coupled receptors (GPCR), the beta2-adrenergic receptor
      and the m4 and m5 muscarinic receptors, all caused inhibition of MAPK activation
      induced by progesterone. These receptors, upon their activation with the
      respective ligands, might be inducing the release of G(beta)gamma from their
      respective G(alpha), which together with endogenous G(alpha)s-GTP, activate
      adenylyl cyclase. Our results indicate that G(alpha)s plays an important role in
      the maturation process and support previous findings of G(beta)gamma
      participation, suggesting the presence of a mechanism where a constitutively
      activated G(alpha)s subunit, together with the G(beta)gamma heterodimer, both
      maintain high levels of intracellular cAMP levels, blocking the G2/M transition.

PMID- 12211068
TI  - Chromosome condensation in pig oocytes: lack of a requirement for either cdc2
      kinase or MAP kinase activity.
AB  - In this study, butyrolactone I (BL I), a potent and specific inhibitor of cyclin
      dependent kinases (cdk), is shown to inhibit germinal vesicle breakdown (GVBD) in
      pig oocytes. Oocytes treated with 100 microM BL I were arrested in the germinal
      vesicle (GV)-stage and displayed low activity of cdc2 kinase and MAP kinase.
      Nevertheless, chromosome condensation occurred and highly condensed bivalents
      were seen within an intact GV after a 24-hr culture in the presence of BL I. The
      inhibitory effect of BL I on MAP kinase activation during culture was likely
      mediated through a cdk-dependent pathway, since MAP kinase activity present in
      extracts derived from metaphase II eggs was not inhibited by BL I. The block of
      GVBD could be released by treating oocytes with okadaic acid (OA), an inhibitor
      of type 1 and 2A phosphatases; 82% of the oocytes treated with the combination of
      OA/BL I underwent GVBD, and MAP kinase became activated, while cdc2 kinase
      remained inhibited. These results suggest that both chromosome condensation and
      GVBD could occur without activation of cdc2 kinase, whereas an increase in MAP
      kinase activity may be a requisite for GVBD in pig oocytes in conditions when
      cdc2 kinase activation is blocked by BL I.

PMID- 12211069
TI  - Protein serine and threonine phosphorylation, hyperactivation and acrosome
      reaction in in vitro capacitated hamster spermatozoa.
AB  - Monoclonal antibodies against phosphoserine and phosphothreonine were used in the
      present study to investigate the changes in serine and threonine phosphorylation
      respectectively during capacitation of hamster spermatozoa. Immunoblot analysis
      of hamster spermatozoa capacitated in TALP, a medium that supports capacitation,
      showed that a set of four proteins of molecular weight 56, 63, 66, and 100 kDa
      was phosphorylated both at the serine and threonine residues. In addition, five
      other proteins of molecular weight 32, 39, 45, 53, and 61 kDa were phosphorylated
      specifically at the threonine residues. Of these nine proteins, the 100 kDa
      protein showed a time dependent or capacitation-dependent decrease in intensity
      which coincided with the percentage acrosome-reacted spermatozoa. In contrast,
      the 49 and 63 kDa threonine phosphorylated proteins showed increased
      phosphorylation coinciding with capacitation. H8 (a serine and threonine kinase
      inhibitor) had a transient effect on the phosphorylation of these two
      phosphothreonine proteins but inhibited acrosome reaction substantially all
      through the treatment period. Okadaic acid (OA) (a serine and threonine protein
      phosphatase inhibitor) inhibited hyperactivation but had no effect on acrosome
      reaction. In fact, OA stimulated acrosome reaction. Finally the
      immunofluorescence studies indicated localization of the serine phosphorylated
      proteins in tail as well as in head of the capacitated hamster spermatozoa
      whereas the threonine phosphorylated proteins were localized mostly in the tail
      of the spermatozoa. The findings of the present study suggest that
      serine/threonine phosphorylation and the enzymes responsible for regulating the
      level of phosphorylation play an important role in capacitation and capacitation
      associated events namely hyperactivation and acrosome reaction. However, further
      studies are needed in order to establish the exact role of these proteins in
      capacitation of spermatozoa.

PMID- 12211070
TI  - Ran, a GTP-binding protein involved in nucleocytoplasmic transport and
      microtubule nucleation, relocates from the manchette to the centrosome region
      during rat spermiogenesis.
AB  - Ran, a Ras-related GTPase, is required for transporting proteins in and out of
      the nucleus during interphase and for regulating the assembly of microtubules.
      cDNA cloning shows that rat testis, like mouse testis, expresses both somatic and
      testis-specific forms of Ran-GTPase. The presence of a homologous testis-specific
      form of Ran-GTPase in rodents implies that the Ran-GTPase pathway plays a
      significant role during sperm development. This suggestions is supported by
      distinct Ran-GTPase immunolocalization sites identified in developing spermatids.
      Confocal microscopy demonstrates that Ran-GTPase localizes in the nucleus of
      round spermatids and along the microtubules of the manchette in elongating
      spermatids. When the manchette disassembles, Ran-GTPase immunoreactivity is
      visualized in the centrosome region of maturing spermatids. The circumstantial
      observation that fractionated manchettes, containing copurified centrin
      immunoreactive centrosomes, can organize a three-dimensional lattice in the
      presence of taxol and GTP, points to the role of Ran-GTPase and associated
      factors in microtubule nucleation as well as the potential nucleating function of
      spermatid centrosomes undergoing a reduction process. Electron microscopy
      demonstrates the presence in manchette preparations of spermatid centrosomes,
      recognized as such by their association with remnants of the implantation fossa,
      a dense plate observed only at the basal surface of developing spermatid and
      sperm nuclei. In addition, we have found importin beta1 immunoreactivity in the
      nucleus of elongating spermatids, a finding that, together with the presence of
      Ran-GTPase in the nucleus of round spermatids and the manchette, suggest a
      potential role of Ran-GTPase machinery in nucleocytoplasmic transport. Our
      expression and localization analysis, correlated with functional observations in
      other cell systems, suggest that Ran-GTPase may be involved in both
      nucleocytoplasmic transport and microtubules assembly, two critical events during
      the development of functional sperm. In addition, the manchette-to-centrosome Ran
      GTPase relocation, together with the similar redistribution of various proteins
      associated to the manchette, suggest the existence of an intramanchette molecular
      transport mechanism, which may share molecular analogies with intraflagellar
      transport.

PMID- 12211071
TI  - Genotoxicity of naturally occurring indole compounds: correlation between
      covalent DNA binding and other genotoxicity tests.
AB  - 3-Methylindole (3MI), melatonin (Mel), serotonin (Ser), and tryptamine (Tryp)
      were evaluated in vitro for their potential to induce DNA adducts, DNA strand
      breaks, chromosomal aberrations (Abs), inhibition of DNA synthesis, and
      mutations. All compounds produced DNA adducts in calf thymus DNA in the presence
      of rat liver S9. In cultured rat hepatocytes, all produced DNA adducts but none
      induced DNA strand breaks. In Chinese hamster ovary cells, 3MI and Mel produced
      DNA adducts, Abs, and inhibition of DNA synthesis with and without S9, except
      that Mel without S9 did not form adducts. Ser formed DNA adducts, was an
      equivocal Abs inducer, and suppressed DNA synthesis. Tryp induced neither adducts
      nor Abs, but did suppress DNA synthesis with S9. Ser and Tryp were less cytotoxic
      than 3MI and Mel. Mel, Ser, and Tryp failed to induce mutations in Salmonella and
      E. coli strains with or without S9. 3MI and Mel produced DNA adducts but not
      mutations in Salmonella TA100 with S9. 3MI and its metabolite indole 3-carbinol
      also did not induce mutations in a shuttle vector system in human cells. The lack
      of correlation between DNA adducts and other genotoxicity endpoints for these
      indole compounds may be due to the higher sensitivity of the (32)P-postlabeling
      adduct assay or it may indicate that the indole-DNA adducts per se are not
      mutagenic and are not able to induce strand breaks or alkali-labile lesions. The
      indole-induced Abs may result from cytotoxicity and suppression of DNA synthesis
      with minimal if any contribution from DNA adducts.

PMID- 12211072
TI  - DNA damage assessment by comet assay of human lymphocytes exposed to jet
      propulsion fuels.
AB  - Exposure to jet fuel damages DNA and results in a number of physiological changes
      in liver, lung, immune, and neurological tissue. In this study the single-cell
      gel electrophoresis assay or comet assay was used to compare the DNA damage in
      human peripheral lymphocytes produced by three jet propulsion fuels: JP-8, JP-5,
      and JP-8+100. These fuels consist of complex mixtures of aliphatic, aromatic, and
      substituted naphthalene hydrocarbons. Two exposure times were investigated which
      correspond to estimated occupational exposure times and concentrations of fuels
      were used that were based on previous fuel toxicity studies. Analysis of samples
      for the extent of DNA damage as determined by tail moment and percent tail DNA
      was performed on exposed cells following a brief recovery time. All fuels
      produced significant increases in DNA damage; however, only JP-8+100 was
      genotoxic at the lowest exposure concentration (1:500). At the highest exposure
      concentration (1:75), the mean tail moments for JP-8 and JP-8+100 (32.041 +/-
      2.599 and 45.774 +/- 4.743, respectively) were significantly greater than for JP
      5 (1.314 +/- 0.474). These results indicate that JP-8+100 is the most potent
      inducer of DNA damage in human peripheral lymphocytes and that both JP-8+100 and
      JP-8 are capable of damaging lymphocyte DNA to a greater extent than JP-5.

PMID- 12211073
TI  - Aroclor 1254 alters morphology, survival, and gene expression in Xenopus laevis
      tadpoles.
AB  - PCBs are persistent environmental contaminants that cause a variety of adverse
      health effects in wildlife and humans. This article describes the use of
      signature gene expression patterns that link increased PCB exposure with
      progressive, adverse biological effects. Developing Xenopus laevis tadpoles of
      two age classes were exposed to the PCB mixture Aroclor 1254 for 2 days. Real
      time PCR was used to quantitate mRNA expression for 11 physiologically relevant,
      potential bioindicator genes. Younger tadpoles (5 days postfertilization) were
      resistant to Aroclor 1254 and showed few changes in gross morphology, swimming
      behavior, survival, or gene expression. Older tadpoles (11 days
      postfertilization) were more susceptible to Aroclor 1254. Exposure to 25 and 50
      ppm Aroclor 1254 caused alterations in gross morphology and swimming behavior and
      statistically significant decreases in survival. These tadpoles showed
      statistically significant decreases in gene expression for 9 out of the 11 genes
      measured. Tadpoles exposed to 10 ppm showed incipient health changes but had gene
      expression profiles similar to the tadpoles treated with higher doses of Aroclor
      1254. Tadpoles exposed to 1 ppm did not exhibit any observable adverse health
      effects, yet statistically significant decreases in gene expression occurred in
      these tadpoles (4 out of 11 genes). After prolonged exposure, tadpoles exposed to
      1 and 10 ppm Aroclor 1254 exhibited health effects similar to those exposed to
      higher concentrations. Therefore, changes in expression of specific genes may
      serve not only as molecular bioindicators of Aroclor 1254 exposure but also as
      predictors of impending adverse health effects.

PMID- 12211074
TI  - Mutation analysis of K-ras-2 in liver angiosarcoma and adjacent nonneoplastic
      liver tissue from patients occupationally exposed to vinyl chloride.
AB  - Vinyl chloride (VC) is a potent liver carcinogen that induces angiosarcomas in
      humans and animals. Recent evidence shows that liver tumors from patients with VC
      exposure may have a specific K-ras mutation pattern. This study was performed to
      determine the status of K-ras-2 in liver angiosarcomas (LAS) from workers
      occupationally exposed to VC. We examined the presence of K-ras-2 mutations in 15
      LAS from patients with known exposure to VC (median exposure: 8,260 ppm [range
      3,900- 21,000 ppm]]. In all cases, other risk factors for the development of LAS
      were excluded. Direct DNA sequencing after microdissection of the tumor cells was
      used for the analysis. Heterozygous mutations of K-ras-2 were detected in 8/15
      LAS (53%). Five patients (33%) had a mutation of codon 12 and three of codon 13
      (20%). The most common changes were G-->A transitions in five LAS which lead to
      the substitution of aspartic acid for glycine in the resulting p21 protein. In
      two patients (13%), mutations of the K-ras-2 gene were identified in the adjacent
      nonneoplastic liver tissue. These data indicate that VC induces a high frequency
      of G-->A transitions in human LAS. This mutation pattern is likely a consequence
      of VC-DNA-adduct formation.

PMID- 12211075
TI  - Photoclastogenicity-an improved protocol, its validation, and investigation of
      the photogenotoxicity of DMBA.
AB  - An improved protocol was developed to detect light-induced clastogenic
      photoproducts in Chinese hamster ovary (CHO) cells. Dishes (60 mm) containing
      cells and the test material or vehicle control in 3 mL of phosphate-buffered
      saline were exposed to light using a SUNTEST CPS solar simulation unit.
      Importantly, cells were exposed at about 25 cm from the light source, thereby
      allowing a short exposure time of 2 min. With this exposure the assay was
      conducted with lids removed during the UV exposure with minimal risk of
      contamination. After preliminary experiments an exposure of 165.6 mJ/cm(2) UVA:
      17.0 mJ/cm(2) UVB was selected for treatments with the different phototoxins.
      Under these exposure conditions about 10-15% aberrant cells were induced in
      vehicle control cultures with no or minimal cytotoxicity. The well-known
      photoclastogens 8-methoxypsoralen (8-MOP) and chlorpromazine (CLZ) were tested.
      In agreement with published data, 8-MOP and CLZ were clastogenic (lowest observed
      effect level, LOEL, was 0.0159 microg/mL and 1.03 microg/mL, respectively). In
      the absence of UV, 8-MOP was clastogenic at a much higher concentration (LOEL 251
      microg/mL without UV vs. 0.0159 microg/mL with UV) while CLZ was negative up to a
      toxic concentration of 35 microg/mL. 7,12-Dimethylbenz[a]anthracene (DMBA), which
      is photomutagenic in bacteria, was clastogenic at > or =0.005 microg/mL with UV
      light (without S9) and at > or =2.53 microg/mL with S9 (without UV light). These
      results demonstrate the utility of the protocol for the detection of
      photoclastogenicity and expand the characterization of DMBA's photogenotoxic
      activity.

PMID- 12211076
TI  - New measure of DNA repair in the single-cell gel electrophoresis (comet) assay.
AB  - Since its introduction by Ostling and Johanson [1984; Biochem Biophys Res Commun
      123:291-298] and independent modifications by Singh et al. [1990; Exp Cell Res
      175:184-191] and Olive et al. [1988; Radiat Res 112:86-94], the comet assay has
      been widely used in genetic toxicology, environmental biomonitoring, molecular
      and human epidemiology, and clinical investigations. There are still several
      issues to be resolved before the comet assay is accepted as a standard assay for
      detecting DNA damage and repair in a single cell. One of the major issues is the
      proper quantification of DNA damage/repair. The aim of this article is to develop
      a new quantitative measure of DNA damage/repair which is represented in the dose
      time-response surface. We propose to use the second derivative (2D) of the dose
      time-response surface for measuring DNA repair activity. This approach enables us
      to represent the DNA repair activity of cells exposed to a DNA-damaging agent
      with a single number by combining all the information of a dose-time-response
      experiment. The computation procedure includes the application of linear
      regression. An SAS/AF-based program, "Comet Assay," was developed for this
      computation and is freely available on the Internet. We considered the response
      of each of four DNA damage parameters: tail moment, tail length, tail DNA, and
      tail inertia for constructing the dose-time-response surface. Using data from 25
      patients, we observed that 2Ds based on tail moment and tail DNA were highly
      correlated and that tail inertia might provide information on a somewhat
      different aspect of DNA damage/repair.

PMID- 12211077
TI  - Effect of dithiocarbamate pesticide zineb and its commercial formulation,
      azzurro. II. micronucleus induction in immunophenotyped human lymphocytes.
AB  - The frequency of micronuclei was measured in human peripheral B-lymphocytes and
      some T-lymphocyte subpopulations exposed in vitro to 1.0-100.0 microg/ml of the
      dithiocarbamate pesticide zineb and its commercial formulation azzurro. The
      peripheral mononuclear lymphocytes were stimulated in vitro with
      phytohemagglutinin after pesticide treatment and B-lymphocytes and the various T
      lymphocyte subsets were classified by the MAC (morphology, antibody, chromosomes)
      method, which allows the immunological identification of different cell lineages.
      An increased frequency of micronuclei in CD20(+) (P < 0.01), CD3(+) (P < 0.01),
      and CD8(+) lymphocytes (P < 0.01) was observed only when 25.0 microg/ml of zineb
      and azzurro were employed. The frequency of micronuclei in treated CD8(+) cells
      did not differ from treated CD20(+) lymphocytes (P > 0.05). Lower concentrations
      of pesticides did not increase the frequency of micronuclei from that observed in
      control cultures. Furthermore, for both zineb and azzurro cytotoxicity was
      observed at doses higher than 50.0 microg/ml. Significant increases in the
      proportion of CD20(+) (P < 0.01) and CD8(+) cells (P < 0.01) among mitotic and
      interphasic lymphocytes from both zineb- and azzurro-treated cultures were
      observed only when a concentration of 25.0 microg/ml was employed. In contrast,
      significant decreases in the proportion of CD3(+) (P < 0.01) and CD4(+) cells (P
      < 0.01) were found for both mitotic and interphasic lymphocytes from zineb- and
      azzurro-treated cultures. The MAC methodology revealed that among the different
      lymphocyte subpopulations analyzed (CD20, CD3, CD4, and CD8), the induction of
      micronuclei by zineb and its commercial formulation azzurro was restricted to
      CD20(+) B-cells and T-suppressor/cytotoxic CD8(+) lymphocytes.

PMID- 12211078
TI  - Genotoxicity of 5-aminolevulinic and 4,5-dioxovaleric acids in the
      salmonella/microsuspension mutagenicity assay and SOS chromotest.
AB  - 5-Aminolevulinic acid (ALA) is a heme precursor that accumulates in some
      porphyric disorders and in lead poisoning which can undergo metal-catalyzed
      oxidation producing reactive oxygen species and the keto-aldehyde, 4,5
      dioxovaleric acid (DOVA). Evidence in vitro of ALA-induced DNA lesions suggests
      that ALA and DOVA have mutagenic potential that could possibly contribute to an
      increased frequency of hepatocellular carcinoma (HCC) in patients with acute
      intermittent porphyria (AIP). In this study, we evaluated the genotoxic potential
      of ALA and DOVA. In the absence of exogenous metabolic activation, ALA and DOVA
      were mutagenic in Salmonella typhimurium tester strain TA104. ALA was also
      mutagenic in S. typhimurium TA102, but not in TA98, TA100, or TA1535, indicating
      an oxidative mechanism. Removal of H(2)O(2) with catalase gave only partial
      protection, suggesting generation of other mutagenic species. Both ALA and DOVA
      damaged the DNA of Escherichia coli PQ37, inducing the SOS response detected by
      an increase in beta-galactosidase activity. These results verified the potential
      mutagenic activity of ALA and DOVA and reinforce the hypothesis that DNA damage
      induced by ALA may be associated with the development of HCC in individuals
      suffering from AIP.

PMID- 12211079
TI  - Dietary folate deficiency enhances induction of micronuclei by arsenic in mice.
AB  - Folate deficiency increases background levels of DNA damage and can enhance the
      genotoxicity of chemical agents. Arsenic, a known human carcinogen present in
      drinking water supplies around the world, induces chromosomal and DNA damage. The
      effect of dietary folate deficiency on arsenic genotoxicity was evaluated using a
      mouse peripheral blood micronucleus (MN) assay. In duplicate experiments, male
      C57Bl/6J mice were fed folate-deficient or folate-sufficient diets for 7 weeks.
      During week 7, mice on each diet were given four consecutive daily doses of
      sodium arsenite (0, 2.5, 5, or 10 mg/kg) via oral gavage. Over the course of the
      study the folate-deficient diet produced an approximate 60% depletion of red
      blood cell folate. Folate deficiency by itself was associated with small but
      significant increases in MN in normochromatic erythrocytes (NCEs) and
      polychromatic erythrocytes (PCEs). Arsenic exposure was associated with
      significant increases in MN-PCEs in both folate-deficient and folate-sufficient
      mice. MN-PCE frequencies at the 10 mg/kg dose of arsenic were increased 4.5-fold
      over vehicle control in folate-deficient mice and 2.1-fold over control in folate
      sufficient mice. At the 5 and 10 mg/kg doses of arsenic, MN-PCE levels were
      significantly higher (1.3-fold and 2.4-fold, respectively) in folate-deficient
      mice compared to folate-sufficient mice. Very few MN from either control or
      treated animals in either experiment exhibited kinetochore immunostaining,
      suggesting that the MN were derived from chromosome breakage rather than from
      whole chromosome loss. These results indicate that folate deficiency enhances
      arsenic-induced clastogenesis at doses of 5 mg/kg and higher.

PMID- 12211082
TI  - Neutralization of neutrophin-3 in the ventral tegmental area or nucleus accumbens
      differentially modulates cocaine-induced behavioral plasticity in rats.
AB  - These experiments were designed to assess the influence of neurotrophin-3 (NT-3)
      and brain-derived neurotrophic factor (BDNF) in the mesoaccumbens dopamine system
      on the initiation of behavioral sensitization to cocaine. A neutralizing antibody
      for NT-3, BDNF or their vehicle was administered into the ventral tegmental area
      (VTA) or nucleus accumbens prior to each of four daily injections of 15 mg/kg
      cocaine. Behavioral sensitization was operationally defined as a significant
      increase in the behavioral response to cocaine relative to the first daily
      injection. Results indicated that the NT-3 antibody had differential effects when
      administered into the VTA or nucleus accumbens. Intra-VTA microinjection of anti
      NT-3 resulted in enhanced sensitization to repeated cocaine injections in that
      the cocaine-induced behavioral response in the anti-NT-3 group was significantly
      greater than the vehicle group following the second and third daily injections of
      cocaine. Administration of anti-NT-3 into the nucleus accumbens increased the
      behavioral response to cocaine over all 4 days of cocaine administration, with no
      sensitization of this behavioral response. In contrast, pretreatment with anti
      BDNF into the VTA or nucleus accumbens had no influence on the initiation of
      behavioral sensitization to cocaine. Taken together, these data indicate that
      neutralization of NT-3 in the VTA enhances cocaine-induced behavioral
      sensitization, while administration of the NT-3 antibody into the nucleus
      accumbens increases the hyperactive behavioral response induced by cocaine but
      impairs the further development of behavioral sensitization.

PMID- 12211081
TI  - Augmentation by zinc of NMDA receptor-mediated synaptic responses in CA1 of rat
      hippocampal slices: mediation by Src family tyrosine kinases.
AB  - Normal neuronal activity results in the release of zinc from the synaptic
      vesicles of glutamatergic terminals and subsequent entry into postsynaptic
      neurons. Although the exact physiological role of zinc translocation is currently
      unknown, it is very likely that intracellular zinc exerts long-term modulatory
      effects upon synaptic transmission since zinc affects various molecules involved
      in signaling pathways. In this study we used rat hippocampal slices to examine
      the effect of zinc on glutamatergic synaptic transmission in the Schaffer
      collateral-CA1 synapses. Following a 10-min exposure to 0.3-1 mM zinc, the
      magnitude of NMDA receptor-mediated field excitatory postsynaptic potentials
      (fEPSP) gradually increased over the subsequent 30-40 min. In contrast, the
      magnitude of AMPA/kainate receptor-mediated fEPSPs remained unchanged. The
      selective potentiation of NMDA receptor-mediated fEPSPs by zinc was unlikely to
      be a presynaptic event, since the degree of paired-pulse facilitation was
      unaltered. Interestingly, the specific Src family tyrosine kinase inhibitor PP2
      completely blocked zinc-induced potentiation of NMDA receptor-mediated fEPSP
      while the inactive analog PP3 had no effect, thereby suggesting the involvement
      of Src family tyrosine kinases. Furthermore, zinc exposure increased levels of
      total and tyrosine-phosphorylated forms of NR2A and NR2B in a PP2-dependent
      manner in both hippocampal slices and cell cultures. In addition, zinc treatment
      of hippocampal cultures increased the levels of tyrosine phosphorylation at the
      two positive regulatory sites of Src family tyrosine kinases. Our results
      demonstrate that zinc increases NMDA receptor function via Src family tyrosine
      kinase-mediated increases of NR2A and 2B tyrosine phosphorylation. We speculate
      that intense release of endogenous synaptic zinc may potentiate NMDA receptor
      mediated transmission in zinc-containing glutamatergic pathways by a similar
      mechanism.

PMID- 12211083
TI  - Specificity of synapse formation between Lymnaea heart motor neuron and muscle
      fiber is maintained in vitro in a soma-muscle configuration.
AB  - Precise neuronal connectivity during development is subservient to all nervous
      system functions in adult animals. However, the cellular mechanisms that
      mastermind this neuronal connectivity remain largely unknown. This lack of
      fundamental knowledge regarding nervous system development is due in part to the
      immense complexity of mammalian brain, as cell-cell interactions between defined
      sets of pre- and postsynaptic partners are often difficult to investigate
      directly. In this study, we developed a novel model system which has allowed us
      to reconstruct synapses between identified motor neurons and their target heart
      muscle cell in a soma-muscle configuration. Utilizing this soma-myocardial cell
      synapse model, we demonstrate that synapses between somata and heart muscle cells
      can be reconstructed in cell culture. The soma-myocardial cell synapses required
      12-24 h to develop and thus differed temporally from conventional neuromuscular
      synapses (seconds to a few minutes). We also demonstrate that the synapses are
      target cell-type-specific and are most likely independent of transmitter
      phenotypic characteristics of presynaptic neurons.

PMID- 12211084
TI  - GBR-12909 effect on dopamine outflow depends on phosphorylation in the caudate
      nucleus of the rat.
AB  - Modulation of the dopamine (DA) transporter inhibitor GBR-12909 effect on DA
      release by protein kinases and protein phosphatases was studied in slices of the
      rat caudate nucleus measuring DA outflow in the superfusate of static chambers.
      Activation of protein kinase A and C markedly enhanced the effect of GBR-12909,
      whereas protein kinase inhibition by H7 reduced the GBR-12909 effect. Inhibition
      of protein phosphatases (PPP) 1 and 2A by okadaic acid did not modify basal
      outflow of DA. However, after the addition of okadaic acid a dramatic and
      biphasic effect was found when DA outflow was enhanced by GBR-12909. Inhibition
      of PPP 2A enhanced extracellular DA levels, while inhibition of PPP 1 and 2A
      completely abolished the effect of GBR-12909. In contrast to tetrodotoxin, the
      voltage-activated calcium channel blocker omega-conotoxin MVIIC inhibited GBR
      12909 effects on DA outflow. Additionally, in aCSF devoid of calcium GBR-12909
      did not increase DA liberation. These results suggest a complex and strong
      influence of phosphorylation on GBR-12909 effects on calcium channel-dependent DA
      outflow at low-affinity piperazine binding sites in slices of the rat caudate
      nucleus in vitro.

PMID- 12211085
TI  - Brain DA D2 receptors predict reinforcing effects of stimulants in humans:
      replication study.
AB  - We had shown that striatal DA D2 receptors levels predicted the reinforcing
      responses to the psychostimulant drug methylphenidate in nondrug-abusing
      subjects. Here, we assessed the replicability of this finding. We measured D2
      receptors with PET and [(11)C]raclopride (twice to determine stability) in seven
      nondrug-abusing subjects to assess if they predicted the self-reports of "drug
      liking" to intravenous methylphenidate (0.5 mg/kg). DA D2 measures were
      significantly correlated with "drug-liking" in both evaluations (r = 0.82 and r =
      0.78); subjects with the lowest levels reported the higher ratings of "drug
      liking" and vice versa. These results replicate our previous findings and provide
      further evidence that striatal DA D2 receptors modulate reinforcing responses to
      stimulants in humans and may underlie predisposition for drug self
      administration.

PMID- 12211086
TI  - Food restriction modulates amphetamine-conditioned place preference and nucleus
      accumbens dopamine release in the rat.
AB  - Food restriction has been shown to increase self-administration of
      psychostimulants, including cocaine and amphetamine (AMPH). Consistent with this,
      food-restricted rats are more sensitized to the rewarding effects of cocaine as
      measured by conditioned place preference (CPP). This study investigated whether
      moderate food restriction in rats (15 g/day) results in an increased CPP,
      relative to ad libitum-fed controls, to a second psychostimulant, AMPH.
      Conditioning trials consisted of six alternating injections of i.p. AMPH (0.425
      6.8 mg/kg) and i.p. saline, paired with distinct environments. On Day 7, a drug
      free 20-min choice test for environment was carried out to assess CPP. 0.85 mg/kg
      AMPH significantly increased CPP in food-restricted vs. ad libitum-fed rats. At
      1.7 and 3.4 mg/kg AMPH, food-restricted rats showed decreased CPP, but increased
      locomotor activity, relative to ad libitum fed controls. To evaluate whether an
      alteration in extracellular fluid DA levels in the nucleus accumbens (NAc) core
      could account for these behavioral alterations, DA release was measured by
      microdialysis. DA release to a single acute i.p. injection of either 0.85 or 1.7
      mg/kg AMPH was comparable in food-restricted and ad libitum fed rats. However, ad
      libitum fed rats demonstrated conditioned DA release after an AMPH conditioning
      paradigm analogous to the CPP paradigm, whereas food-restricted rats demonstrated
      no conditioned DA release. In conclusion, altered DA release in the nucleus
      accumbens core is not a primary effect of moderate food restriction and cannot
      completely account for either the altered CPP behavior or enhanced locomotor
      activity observed in this study.

PMID- 12211087
TI  - Hippocampal expression of c-fos is not essential for spatial learning.
AB  - The formation of long-term memory is thought to involve underlying changes in
      synaptic strength. Many studies have focused on the mechanisms of spatial
      learning behavior in mammals that is critically dependent on the proper function
      of the hippocampus. Because of the enduring nature of long-term memory, it is
      thought that gene expression is involved in this process. The immediate early
      gene (IEG) c-fos encodes a transcription factor. The c-Fos proteins form
      heterodimeric proteins with the c-Jun family proteins and the resulting AP-1
      transcription complex plays a key role in coupling short-term events elicited by
      stimuli received at the cell membrane to long-term neuroplastic changes by
      regulating gene expression. c-fos is induced in the hippocampus after spatial
      learning. Despite this knowledge, the precise role of c-fos in memory formation
      and the underlying mechanisms remain unknown. To start investigating the role of
      c-fos in learning and memory and underlying mechanisms, we evaluated spatial
      learning capabilities using mice carrying a hippocampal region-specific mutation
      of c-fos. We found that the c-fos mutant mice exhibit normal spatial learning
      behaviors in both the Morris water maze and the Barnes maze tests compared to
      control mice. Our results suggest that hippocampal c-fos expression is not
      essential for spatial learning.

PMID- 12211089
TI  - 5-HT(1A) receptor imaging in the human brain: effect of tryptophan depletion and
      infusion on [(18)F]MPPF binding.
AB  - The 5-HT(1A) receptor has been implicated in a variety of physiological
      processes, psychiatric disorders, and neurodegenerative disorders. [(18)F]MPPF is
      a useful radioligand for quantitative imaging of 5-HT(1A) receptors in human
      subjects. Previous studies have shown that the binding of some radioligands is
      sensitive to changes in neurotransmitter concentration, whereas in other cases,
      binding is not affected. In the present study we investigated if [(18)F]MPPF
      binding to the 5-HT(1A) receptor is sensitive to changes in 5-HT. Changes in 5-HT
      levels were achieved by influencing its synthesis through tryptophan depletion,
      including a tryptophan-free amino acid drink 4.5 h prior to the PET scan and
      tryptophan infusion (10 mg/ml, 50 mg/kg, 30 min, starting 60 min prior to the PET
      scan). Binding of [(18)F]MPPF in the brain of six healthy, male volunteers was
      compared in these two conditions. Mean binding potentials in the medial temporal
      cortex, cortical regions, and raphe nucleus did not significantly differ between
      the two conditions. The results of the study show that, under the experimental
      conditions used, [(18)F]MPPF binding was not affected. It is hypothesized that
      the increases in 5-HT levels needed to produce a measurable effect on [(18)F]MPPF
      binding would be significantly greater than that possible with tryptophan
      manipulation. Therefore, in pathological conditions, where such large increases
      in 5-HT levels are not expected, [(18)F]MPPF seems a useful ligand to measure 5
      HT(1A) receptor distribution without the interference of endogenous 5-HT.

PMID- 12211088
TI  - Fos expression in GABAergic cells and cells immunopositive for NMDA receptors in
      the inferior and superior colliculi following audiogenic seizures in rats.
AB  - Given the evidence that the inferior colliculus (IC) and superior colliculus (SC)
      seem to play key roles in connecting auditory pathways and seizure output
      pathways in the neuronal network for audiogenic seizures (AS) in rats, we
      examined Fos activation in GABAergic cells and cells immunopositive for glutamate
      N-methyl-D-aspartate (NMDA) receptors in the IC and SC following AS using the
      double-labeling procedure. Generalized tonic-clonic seizures (GTCS), which
      developed as an advanced form of AS in some of the susceptible rats, induced an
      increase in Fos expression in three IC substructures-the dorsal cortex of IC
      (DCIC), central nucleus of IC (CIC), and external cortex of IC (ECIC)-and in one
      SC substructure, the deep gray layer of SC (DpG). Compared with the rats showing
      GTCS, rats exhibiting wild running (WR) without proceeding to GTCS showed a
      different pattern of AS-induced Fos expression. The DpG in the WR animals showed
      no significant increase in the levels of Fos-like immunoreactivity. The degrees
      of Fos activation that occurred in GABAergic cells and cells immunopositive for
      NMDA receptors were similar in the DCIC, CIC, ECIC, and DpG following AS. These
      results suggest that Fos activation in the DpG is involved in the development
      from WR to GTCS in AS-susceptible rats. They also provide some evidence that some
      GABAergic neurons in the IC and SC and glutamatergic afferents (via NMDA
      receptors) to these structures are activated by AS.

PMID- 12211090
TI  - Influence of aging and social isolation on changes in brain monoamine turnover
      and biosynthesis of rats elicited by novelty stress.
AB  - Aging is a risk factor of human depression. Middle-aged or older men are
      vulnerable to adverse life events and an absence of social contact and easily
      become depressed. In the present study, we investigated the influence of aging on
      responses to life events in socially isolated conditions. We applied isolation
      rearing (4 W) to two age groups, older (18 M) and younger (11 W), of male F344
      rats that had been reared in a group and then examined responses to novelty
      stress (20 min). Changes in brain monoamines and their metabolites such as
      dopamine (DA), serotonin (5-HT), dihydroxyphenylacetic acid (DOPAC), homovanilic
      acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in six regions:
      the prefrontal cortex, nucleus accumbens, hippocampus, amygdala, midbrain, and
      raphe nuclei. MANOVA was carried out for rearing condition, age, and novelty
      stress. Isolation significantly changed monoamines and their metabolites, except
      in amygdala and raphe nuclei. Aging significantly altered them in all regions,
      although novelty stress did not. In the amygdala and midbrain, isolation
      significantly changed monoamine biosynthesis, with monoamine turnover remaining
      unchanged. In the prefrontal cortex and nucleus accumbens, aging significantly
      altered turnover, while biosynthesis remained unchanged. Novelty stress
      significantly varied only the turnover in the prefrontal cortex. The interaction
      between isolation and aging indicated that aging influences changes in turnover
      and biosynthesis elicited by isolation primarily at the center of the mesolymbic
      DA system, the midbrain, and in raphe nuclei of the 5-HT system. In peripheral
      regions of the mesolymbic system, aging primarily affects changes in turnover
      induced by isolation.

PMID- 12211091
TI  - Predosing with the unlabeled "inactive" enantiomer as a tool for improvement of
      the PET signal.
AB  - In this study we investigated whether the PET signal of labeled (S)-citalopram
      could be improved by predosing with the unlabeled distomer (R)-citalopram. Ten
      minutes before intravenous injection of 1.5 MBq [(3)H]-(S)-citalopram, rats were
      given i.v. 0.9% saline, 16 or 24 microg (R)-citalopram. Sixty minutes after
      injection of [(3)H]-(S)-citalopram, the brains were dissected into eight regions.
      The binding obtained in each brain region was compared to cerebellum as a
      reference region. Predosing with saline, 16 and 24 microg (R)-citalopram yielded
      thalamus/cerebellum ratios of 1.6 +/- 0.12, 1.6 +/- 0.12, and 1.1 +/- 0.26 (means
      +/- SD), respectively. It is concluded that the nonspecific binding of
      radiolabeled (S)-citalopram cannot be reduced by predosing with the 150 times
      less active enantiomer (R)-citalopram, possibly due to the pool of nonspecific
      sites being too large for blocking.

PMID- 12211092
TI  - Effect of SA4503 on the electrically evoked release of (3)H-acetylcholine from
      striatal and hippocampal rat brain slices.
AB  - Recent microdialysis data has shown that the systemic administration of the
      selective sigma(1) receptor agonist SA4503 increases the extracellular levels of
      acetylcholine (ACh) in the hippocampus, but not the striatum, of freely moving
      rats. In the present study, we examined the effect of SA4503 on the electrically
      evoked release of (3)H-ACh in rat brain slices isolated from the hippocampus and
      striatum. At 100 and 300 nM concentrations of SA4503, the electrically evoked
      release of (3)H-ACh was increased in hippocampal but not striatal slices.
      Concentrations below 100 nM did not alter the electrically evoked release of (3)H
      ACh in either brain area. These results tentatively suggest that the increase in
      extracellular ACh levels observed in the hippocampus after the systemic
      administration of SA4503 could in part be related to its interaction with
      sigma(1) receptors in the hippocampus.

PMID- 12211093
TI  - Intravenous self-administration of amphetamine is increased in a rat model of
      depression.
AB  - Affective disorders and substance abuse frequently coexist, yet few previous
      studies have examined drug self-administration using animal models of depression.
      The olfactory-bulbectomized rat is a well-established model that exhibits a high
      degree of neurochemical similarity to depression. Olfactory bulbectomy (OBX)
      increases dopamine receptor densities in the ventral striatum, which may increase
      the reinforcing effects of drugs of abuse. Experiments were designed to test the
      hypotheses that acquisition and stable self-administration of amphetamine would
      be increased in bulbectomized rats. In the first experiment, rats underwent
      bilateral OBX or sham surgery and intravenous jugular catheters were implanted 12
      14 days later. Acquisition was examined using a standard operant paradigm
      involving a nose-poke response for a very low dose of D-amphetamine sulfate (12
      microg/infusion, IV). A separate group of rats received coinfusions of sulpiride.
      In a second experiment designed to minimize differences in acquisition and
      examine stable self-administration, lever pressing for a low (0.10 mg/kg, IV) or
      high (0.25 mg/kg, IV) dose of D-amphetamine sulfate was measured in rats
      pretrained to lever press for food. Bulbectomized rats acquired the self
      administration of very low dose amphetamine faster than sham-operated rats and
      this effect was reversed by sulpiride coinfusion. Stable self-administration of
      the low dose of amphetamine was also markedly increased in bulbectomized rats.
      The findings reveal the utility of the OBX model for studying the neurobiological
      basis of depression and drug abuse comorbidity and support the hypothesis that
      neurochemical abnormalities associated with depression may enhance the addictive
      properties of some drugs of abuse.

PMID- 12211094
TI  - Fear-like biochemical and behavioral responses in rats to the predator odor, TMT,
      are dependent on the exposure environment.
AB  - Several laboratories have reported that exposure to predator odor can result in
      stress-like effects in rodents. While some laboratories have reported fear-like
      alterations in behavior, other laboratories, including our own, have failed to
      consistently observe fearful behaviors in rats exposed to the predator odor TMT.
      One potential contributing factor to this discrepancy is the handling of the rat
      and its test environment. In the current report, we examine biochemical,
      endocrinological, and behavioral effects of TMT in two distinct open fields: one
      small, familiar, and dimly lit, while the other was large, novel, and brightly
      lit. Only exposure to TMT in the large, novel open field resulted in fearful
      behavior; however, no increase in dopamine turnover was noted compared to no odor
      and control odor rats. As expected, the different open fields resulted in some
      biochemical and behavioral differences, including more horizontal locomotion and
      less grooming, higher serum corticosterone, and increased dopamine turnover in
      the ventral prefrontal cortex in the large open field. Finally, compared to the
      same open field controls, TMT exposure elevated rat serum corticosterone levels
      in both open fields and dopamine turnover in the dorsal and ventral medial
      prefrontal cortex and amygdala of rats only in the small, familiar open field.
      These results indicate that the TMT-induced biochemical activation of may occur
      without detectable fearful behaviors and may indicate a mechanism that prepares
      the animal for the expression of a fearful response if additional provocative
      stimuli are present.

PMID- 12211095
TI  - Phenotypic, ethologically based resolution of spontaneous and D(2)-like vs D(1)
      like agonist-induced behavioural topography in mice with congenic D(3) dopamine
      receptor "knockout".
AB  - Uncertainty as to the functional role of the D(3) dopamine receptor, due
      primarily to a paucity of selective agonists or antagonists, is being addressed
      in mice with targeted gene deletion ("knockout") thereof. This study describes,
      for the first time, the phenotype of congenic D(3)-null mice. Initially, 129/Sv x
      C57BL/6 D(3)-null mice were backcrossed 14 times onto C57BL/6; they were then
      assessed using an ethologically based approach which resolves all topographies of
      behaviour within the mouse repertoire. The ethogram of D(3)-null mice, on
      comparison with wildtypes, was characterised by no alteration in any topography
      of behaviour over an initial period of exploration; subsequent assessment over
      several hours revealed only increased rearing among females due to delayed
      habituation. Low doses of the selective D(2)-like agonist RU 24213 (0.016-0.25
      mg/kg) inhibited topographies of exploratory behaviour; this effect was
      diminished in D(3)-null mice only when investigated following prolonged
      habituation, and then only for certain topographies of behaviour, primarily
      sniffing and rearing. High doses of RU 24213 (0.1-12.5 mg/kg) induced stereotyped
      sniffing and "ponderous" locomotion, while the selective D(1)-like agonist SK&F
      83959 (0.016-2.0 mg/kg) promoted characteristic grooming syntax; these effects
      did not differ materially between the genotypes. When examined topographically on
      an essentially congenic C57BL/6 background (<0.005% 129/Sv), the resultant
      phenotype indicated essential conservation of the mouse ethogram, high-dose D(2)
      like stimulatory effects, and D(1)-like stimulatory effects in the absence of
      D(3) receptors. A role for D(3) receptors in inhibitory processes appeared
      topographically circumscribed and only when baseline levels of behaviour were
      low.

PMID- 12211096
TI  - Prediction and assessment of extrapyramidal side effects induced by risperidone
      based on dopamine D(2) receptor occupancy.
AB  - In the present study, we attempted to predict the risk of extrapyramidal side
      effects of a selective monoaminergic antagonist, risperidone, by analyzing the
      correlation between the dopamine D(2) receptor occupancy and the degree of
      extrapyramidal side effects of the drug. The occupancies of D(2) and 5-HT(2)
      receptors at various doses of risperidone were calculated by means of a receptor
      occupancy theory. The extrapyramidal side effects after administration of
      risperidone were attempted to predict by theoretical analysis of the correlation
      between the calculated occupancies and the evidence of extrapyramidal symptoms
      using a ternary complex model. The pharmacokinetic/pharmacodynamic analysis
      utilized the data concerning the pharmacokinetics of risperidone and 9
      hydroxyrisperidone (active metabolite), their binding affinities with D(2) and 5
      HT(2) receptors, and the clinical evidence of extrapyramidal symptoms
      (Extrapyramidal Symptom Rating Scale: ESRS), gathered from the literature. The
      mean occupancy of 5-HT(2) receptors after the administration of regular doses of
      risperidone was suggested to be more than 90%, whereas the mean occupancy of D(2)
      receptors varied between 50-80%, depending on the dose. The correlation between
      the occupancy of D(2) receptors and the extrapyramidal symptoms could be
      successfully analyzed with a ternary complex model, showing the predictability of
      the model for the extrapyramidal side effects of risperidone. Since the estimated
      risk of the extrapyramidal side effects varied with the dose, the present method
      of predicting the extrapyramidal side effects of risperidone may provide a basis
      for developing a rational dosing regimen for the drug.

PMID- 12211097
TI  - Effect of glutamatergic systems on in vivo binding of [(125)I]beta-CIT in the
      brain of a rat model of Parkinson's disease.
AB  - The effect of MK-801, a noncompetitive NMDA receptor antagonist, on both in vivo
      and in vitro binding of [(125)I]beta-CIT (RTI-55) was investigated in a rat model
      of Parkinson's disease. The binding experiments were performed 2 weeks after
      unilateral intranigral microinjection of 6-hydroxydopamine (6-OHDA). In the in
      vitro binding study, no alterations in [(125)I]beta-CIT binding in rat brain
      sections were observed after addition of MK-801, 0.03 microM or 3 microM, to the
      incubation medium. However, in vivo [(125)I]beta-CIT binding to the dopamine
      transporter in both nonlesioned and 6-OHDA-lesioned striatum was significantly
      increased by pretreatment with MK-801. In vivo [(125)I]beta-CIT binding to the
      serotonin (5HT) transporter in nonlesioned cerebral cortex, hypothalamus, and
      thalamus was also significantly increased by MK-801. However, the degree of
      change in the specific binding of [(125)I]beta-CIT induced by MK-801 was smaller
      in the lesioned cerebral cortex. Kinetic analysis, by a simplified three
      compartment model with the cerebellum as the reference region, revealed that
      these alterations in the in vivo [(125)I]beta-CIT binding induced by MK-801 were
      mainly due to changes in the rate constants of in vivo binding, the input rate
      constant, k(3), and the output rate constant, k(4). These results indicate that
      the glutamatergic system significantly affects the function of dopamine
      transporters in the degenerated dopaminergic neurons in Parkinson's disease.

PMID- 12211098
TI  - Chronic repetitive transcranial magnetic stimulation (rTMS) does not affect
      tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) expression in rats
      in vivo.

PMID- 12211099
TI  - Embryonic wound healing by apical contraction and ingression in Xenopus laevis.
AB  - We have characterized excisional wounds in the animal cap of early embryos of the
      frog Xenopus laevis and found that these wounds close accompanied by three
      distinct processes: (1) the assembly of an actin purse-string in the epithelial
      cells at the wound margin, (2) contraction and ingression of exposed deep cells,
      and (3) protrusive activity of epithelial cells at the margin. Microsurgical
      manipulation allowing fine control over the area and depth of the wound combined
      with videomicroscopy and confocal analysis enabled us to describe the kinematics
      and challenge the mechanics of the closing wound. Full closure typically occurs
      only when the deep, mesenchymal cell-layer of the ectoderm is left intact; in
      contrast, when deep cells are removed along with the superficial, epithelial cell
      layer of the ectoderm, wounds do not close. Actin localizes to the superficial
      epithelial cell-layer at the wound margin immediately after wounding and forms a
      contiguous "purse-string" in those cells within 15 min. However, manipulation and
      closure kinematics of shaped wounds and microsurgical cuts made through the purse
      string rule out a major force-generating role for the purse-string. Further
      analysis of the cell behaviors within the wound show that deep, mesenchymal cells
      contract their apical surfaces and ingress from the exposed surface. High
      resolution time-lapse sequences of cells at the leading edge of the wound show
      that these cells undergo protrusive activity only during the final phases of
      wound closure as the ectoderm reseals. We propose that assembly of the actin
      purse-string works to organize and maintain the epithelial sheet at the wound
      margin, that contraction and ingression of deep cells pulls the wound margins
      together, and that protrusive activity of epithelial cells at the wound margin
      reseals the ectoderm and re-establishes tissue integrity during wound healing in
      the Xenopus embryonic ectoderm.

PMID- 12211100
TI  - Myosin II dynamics in Dictyostelium: determinants for filament assembly and
      translocation to the cell cortex during chemoattractant responses.
AB  - In the simple amoeba Dictyostelium discoideum, myosin II filament assembly is
      regulated primarily by the action of a set of myosin heavy chain (MHC) kinases
      and by MHC phosphatase activity. Chemoattractant signals acting via G-protein
      coupled receptors lead to rapid recruitment of myosin II to the cell cortex, but
      the structural determinants on myosin necessary for translocation and the second
      messengers upstream of MHC kinases and phosphatases are not well understood. We
      report here the use of GFP-myosin II fusions to characterize the domains
      necessary for myosin II filament assembly and cytoskeletal recruitment during
      responses to global stimulation with the developmental chemoattractant cAMP.
      Analysis performed with GFP-myosin fusions, and with latrunculin A-treated cells,
      demonstrated that F-actin binding via the myosin motor domain together with
      concomitant filament assembly mediates the rapid cortical translocation observed
      in response to chemoattractant stimulation. A "headless" GFP-myosin construct
      lacking the motor domain was unable to translocate to the cell cortex in response
      to chemoattractant stimulation, suggesting that myosin motor-based motility may
      drive translocation. This lack of localization contrasts with previous work
      demonstrating accumulation of the same construct in the cleavage furrow of
      dividing cells, suggesting that recruitment signals and interactions during
      cytokinesis differ from those during chemoattractant responses. Evaluating
      upstream signaling, we find that iplA null mutants, devoid of regulated calcium
      fluxes during chemoattractant stimulation, display full normal chemoattractant
      stimulated myosin assembly and translocation. These results indicate that calcium
      transients are not necessary for chemoattractant-regulated myosin II filament
      assembly and translocation.

PMID- 12211102
TI  - Laminin-1 increases motility, path-searching, and process dynamism of rat and
      mouse Muller glial cells in vitro: implication of relationship between cell
      behavior and formation of retinal morphology.
AB  - Spatial correlation was observed between the localization of laminin-1 at the
      inner limiting membrane (ILM) and extensive Muller glial process arborization in
      the same area, as demonstrated by immunolabeling of Muller glial processes and
      laminin-1 in rat retinae in situ. To test if this spatial correlation is due to a
      functional relationship, we investigated the impact of laminin-1 on the motility
      of cultured primary rat and mouse retinal Muller glial cells by statistical
      analysis of computer-controlled videomicroscopic time-lapse images. We
      demonstrate that laminin-1 increases motility and path-searching activity of
      Muller cells in vitro and it also enhances the cells' process
      formation/withdrawal dynamism. The increase in path-searching activity and cell
      process dynamism indicates that there is a functional relationship between
      laminin-1 and Muller glial cells presumably involving signaling towards the
      cytoskeleton. We hypothesize that laminin-1 is involved in process arborization
      of Muller cells at the vitread border of the retina resulting in the formation of
      the functional barrier made up of Muller glial endfeet.

PMID- 12211101
TI  - Localised depletion of polymerised actin at the front of Walker carcinosarcoma
      cells increases the speed of locomotion.
AB  - Spontaneously migrating Walker carcinosarcoma cells usually form lamellipodia at
      the front. Combined treatment with 10(-5)M colchicine and 10(-7)M latrunculin A
      produces large defects in the cortical F-actin layer at the leading front and
      suppresses lamellipodia. However, the cortical actin layer at the rear is intact
      and shows myosin IIA accumulation. These cells, showing no or little detectable
      cortical F-actin at the front and no morphologically recognisable protrusions,
      migrate faster than control cells with lamellipodia and an intact cortical actin
      layer. This documents that the cortical actin layer or actin-powered force
      generation at the front is redundant for locomotion. Colchicine and latrunculin A
      have synergistic effects in compromising the cortical layer at the front and in
      increasing the speed of locomotion, but antagonistic effects on the relative
      amount of F-actin per cell. Colchicine but not latrunculin A, can increase the
      proportion of polarised and locomoting cells under appropriate conditions.
      Locomotion and polarity of cells treated with latrunculin A and colchicine is
      inhibited at latrunculin A concentrations >10(-7)M, by the myosin inhibitor BDM
      or the ROCK inhibitor Y-27632. Colchicine and Y-27632 have antagonistic effects
      on polarity and the speed of locomoting cells. The data show that locomotion of
      metazoan cells, which normally form lamellipodia, can be driven by actomyosin
      contraction behind the front (cell body, uropod). They are best compatible with a
      cortical contraction/frontal expansion model, but they are not compatible with
      models implying that actin polymerisation or actomyosin contraction at the front
      drive locomotion of the cells studied.

PMID- 12211103
TI  - Reorganization and translocation of the ectoplasmic cytoskeleton in the leech
      zygote by condensation of cytasters and interactions of dynamic microtubules and
      actin filaments.
AB  - The formation and bipolar translocation of an ectoplasmic cytoskeleton of rings
      and meridional bands was studied in interphase zygotes of the glossiphoniid leech
      Theromyzon trizonare. Zygotes consisted of a peripheral organelle-rich ectoplasm
      and an internal yolk-rich endoplasm. After microinjection of labeled tubulin
      and/or actin, zygotes were examined by time-lapse video imaging,
      immunofluorescence and confocal microscopy. The rings and meridional bands were
      formed by condensation of a network of moving cytasters that represented
      ectoplasmic secondary centers of microtubule and actin filament nucleation. In
      some cases the network of cytasters persisted between the rings. The cytoskeleton
      had an outer actin layer and an inner microtubule layer that merged at the
      irregularly-shaped boundary zone. Bipolar translocation of the rings, meridional
      bands, or the network of cytasters led to accumulation of the cytoskeleton at
      both zygote poles. Translocation of the cytoskeleton was slowed or arrested by
      microinjected taxol or phalloidin, in a dose-dependent fashion. Results of drug
      treatment probably indicate differences in the degree and speed at which the
      cytoskeleton becomes stabilized. Moreover, drugs that selectively stabilized
      either microtubules or actin filaments stabilized and impaired movement of the
      entire cytoskeleton. Microtubule poisons and latrunculin-B failed to disrupt the
      cytoskeleton. It is concluded that the microtubule and actin cytoskeletons are
      dynamic, presumably cross-linked and resistant to depolymerizing drugs. They
      probably move along each other by a sliding mechanism that depends on the
      instability of microtubules and actin filaments.

PMID- 12211104
TI  - Cytoskeletal structure of myoblasts with the mitochondrial DNA 3243A-->G mutation
      and of osteosarcoma cells with respiratory chain deficiency.
AB  - The cytoskeleton, mainly composed of actin filaments, microtubules, and
      intermediate filaments, is involved in cell proliferation, the maintenance of
      cell shape, and the formation of cellular junctions. The organization of the
      intermediate filaments is regulated by phosphorylation and dephosphorylation. We
      examined cell population growth, apoptotic cell death, and the morphology of
      cytoskeletal components in myoblast cultures derived from patients with the 3243A
      ->G mutation in mitochondrial DNA (mtDNA) and from control subjects by means of
      assays detecting cellular nucleic acids, histone-associated DNA fragments and by
      immunolabeling of cytoskeletal components. Population growth was slower in the
      3243A-->G myoblast cultures, with no difference in the amount of apoptotic cell
      death. The organization of vimentin filaments in myoblasts with 3243A-->G was
      disturbed by randomization of filament direction and length, whereas no
      disturbances were observed in the other cytoskeletal proteins. Vimentin filaments
      formed large bundles surrounding the nucleus in mtDNA-less (rho(0)) osteosarcoma
      cells and in osteosarcoma cells after incubation with sodium azide and
      nocodazole. We conclude that defects in oxidative phosphorylation lead to
      selective disruption of the vimentin network, which may have a role in the
      pathophysiology of mitochondrial diseases.

PMID- 12211105
TI  - Arachidonic acid signaling to the cytoskeleton: the role of cyclooxygenase and
      cyclic AMP-dependent protein kinase in actin bundling.
AB  - Cell adhesion to the extracellular matrix via integrins is a primary regulatory
      mechanism for numerous aspects of normal cellular function. However, disruption
      of this interaction can result in pathology. For example, one characteristic of
      transformed cells is loss of adhesion dependence for viability. Adhesion also is
      a necessary step in tumor metastasis. It has been shown previously, in HeLa
      cells, that cell attachment to a gelatin-coated substrate results in the release
      of arachidonic acid, which is metabolized by lipoxygenase. A subsequent cascade
      of lipid second messengers activates protein kinase C, which triggers actin
      polymerization leading to cell spreading. We now demonstrate by inhibitor studies
      and biochemical analysis, a parallel branch of arachidonic acid signaling that
      reorganizes the actin cytoskeleton into small bundles. This branch of the pathway
      is initiated by cyclooxygenase, which generates prostaglandins and causes the
      downstream activation of cyclic AMP-dependent protein kinase. This work
      elucidates a system of interacting signals in which arachidonic acid functions at
      a branch point in cytoskeletal signaling. The lipoxygenase branch provides
      polymerized actin; these actin filaments act as a substrate for the cylooxygenase
      branch to generate actin bundles.

PMID- 12211106
TI  - Actin-based phagosome motility.
AB  - Despite abundant evidence of actin's involvement at the particle internalization
      stage of phagocytosis, little is known about whether phagosomes undergo the same
      type of actin-based motility as observed with endocytic vesicles or such
      intracellular pathogens as Listeria and Shigella. By employing video microscopy
      to follow the fate of latex bead-containing phagosomes within the cytoplasm of
      bone marrow macrophages, we have made the novel observation of actin-based
      phagosome motility. Immunofluorescence microscopy confirmed that phagosomes
      containing IgG-opsonized, bovine serum albumin (or BSA) -coated or uncoated latex
      beads all formed actin-rich rocket tails that persisted only during a brief, 1-2
      min period of actin-based motility. Average speeds of actin-based phagosome
      motility were 0.13 +/- 0.06 microm/s for IgG-coated beads, 0.14 +/- 0.04 microm/s
      for BSA-coated beads, and 0.11+/- 0.03 microm/s for uncoated beads. Moreover, the
      speeds and motile-phase duration of each type of phagosome were comparable to the
      behavior of pinosomes [Merrifield et al., 1999: Nat. Cell Biol. 1:72-74.].
      Determination of optimal conditions for observing and analyzing actin-based
      phagosome motility should facilitate future investigations of phagocytosis and
      phagosome maturation.

PMID- 12211107
TI  - A tissue-specific exon of myosin Va is responsible for selective cargo binding in
      melanocytes.
AB  - Class V myosins are molecular motors used for intracellular transportation and
      organelle tethering. The mouse Myosin Va (MyoVa) is encoded by the dilute locus,
      which is alternatively spliced to generate several tissue specific isoforms. The
      tail of MyoVa is the putative cargo-binding domain. To determine the functions of
      different isoforms of MyoVa and the minimal cargo-binding region, we tagged
      various isoforms and different portions of the mouse MyoVa tail with a green
      fluorescent protein and examined their intracellular localizations in the mouse
      melan-a cells. We found that the amino acid sequence encoded by an alternatively
      spliced exon, exon F, is necessary for the selective binding of MyoVa to
      melanosome. The MyoVa isoforms lacking this amino acid sequence are not targeted
      to the melanosomes, but localized to the perinuclear region instead. These
      findings suggested that MyoVa is able to bind to more than one types of cargos,
      with the selectivities determined by alternative spliced sequences.

PMID- 12211108
TI  - Computer simulation of flagellar movement VIII: coordination of dynein by local
      curvature control can generate helical bending waves.
AB  - Computer simulations have been carried out with a model flagellum that can bend
      in three dimensions. A pattern of dynein activation in which regions of dynein
      activity propagate along each doublet, with a phase shift of approximately 1/9
      wavelength between adjacent doublets, will produce a helical bending wave. This
      pattern can be termed "doublet metachronism." The simulations show that doublet
      metachronism can arise spontaneously in a model axoneme in which activation of
      dyneins is controlled locally by the curvature of each outer doublet microtubule.
      In this model, dyneins operate both as sensors of curvature and as motors.
      Doublet metachronism and the chirality of the resulting helical bending pattern
      are regulated by the angular difference between the direction of the moment and
      sliding produced by dyneins on a doublet and the direction of the controlling
      curvature for that doublet. A flagellum that is generating a helical bending wave
      experiences twisting moments when it moves against external viscous resistance.
      At high viscosities, helical bending will be significantly modified by twist
      unless the twist resistance is greater than previously estimated. Spontaneous
      doublet metachronism must be modified or overridden in order for a flagellum to
      generate the planar bending waves that are required for efficient propulsion of
      spermatozoa. Planar bending can be achieved with the three-dimensional flagellar
      model by appropriate specification of the direction of the controlling curvature
      for each doublet. However, experimental observations indicate that this "hard
      wired" solution is not appropriate for real flagella.

PMID- 12211109
TI  - Amorphin is phosphorylase; phosphorylase is an alpha-actinin-binding protein.
AB  - In a study of myofibrillar proteins, Chowrashi and Pepe [1982: J. Cell Biol.
      94:565-573] reported the isolation of a new, 85-kD Z-band protein that they named
      amorphin. We report that partial sequences of purified amorphin protein indicate
      that amorphin is identical to phosphorylase, an enzyme important in the
      metabolism of glycogen. Anti-amorphin antibodies also reacted with purified
      chicken and rabbit phosphorylase. To explore the basis for phosphorylase's
      (amorphin's) localization in the Z-bands of skeletal muscles, we reacted
      biotinylated alpha-actinin with purified amorphin and with purified phosphorylase
      and found that alpha-actinin bound to each. Radioimmune assays also indicated
      that phosphorylase (amorphin) bound to alpha-actinin, and, with lower affinity,
      to F-actin. Negative staining of actin filaments demonstrated that alpha-actinin
      mediates the binding of phosphorylase to actin filaments. There are several
      glycolytic enzymes that bind actin (e.g., aldolase, phosphofructokinase, and
      pyruvate kinase), but phosphorylase is the first one demonstrated to bind alpha
      actinin. Localization of phosphorylase in live cells was assessed by transfecting
      cultures of quail embryonic myotubes with plasmids expressing phosphorylase fused
      to Green Fluorescent Protein (GFP). This resulted in targeting of the fusion
      protein to Z-bands accompanied by a diffuse pattern in the cytoplasm.

PMID- 12211110
TI  - A talin fragment as an actin trap visualizing actin flow in chemotaxis,
      endocytosis, and cytokinesis.
AB  - A C-terminal 63-kDa fragment of talin A from Dictyostelium discoideum forms a
      slowly dissociating complex with F-actin in vitro. This talin fragment (TalC63)
      has been tagged with GFP and used as a trap for actin filaments in chemotactic
      cell movement, endocytosis, and mitotic cell division. TalC63 efficiently
      sequesters actin filaments in vivo. Its translocation reflects the direction and
      efficiency of an actin flow. Along the body of a migrating Dictyostelium cell,
      this flow is directed from the front to the tail. If during chemotaxis one or two
      new fronts are induced, the flow is always directed away from these fronts. The
      flow thus reflects the re-programming of cell polarity in response to changing
      gradients of chemoattractant. In endocytosis, the fluorescent complexes are
      translocated to the base of a phagocytic or macropinocytic cup. During mitosis,
      the complexes of F-actin with TalC63 accumulate within the midzone of anaphase
      cells. If TalC63 is strongly expressed, the entire cleavage furrow is filled out
      by sequestered actin filaments, and cytokinesis is severely impaired. These cells
      are considered to mimic the phenotype of mutants deficient in the shredding of
      actin filaments that normally occurs in the mid-zone of a dividing cell.

PMID- 12211111
TI  - Pseudopodium dynamics and rapid cell movement in Dictyostelium Ras pathway
      mutants.
AB  - Loss of either of the Ras pathway members RasS or GefB causes growing
      Dictyostelium cells to move aberrantly rapidly. In this study, we describe the
      changes in motility that underlie these phenotypes using computer-assisted 3D
      dynamic image analysis. Unexpectedly, the two mutants use different mechanisms to
      achieve rapid migration. The rasS(-) cells' motility is characterised by highly
      dynamic cell morphology, with rapidly extending and retracting pseudopodia. The
      gefB(-) cells do not have an unusually dynamic morphology, and achieve their
      efficient translocation by the continual remodelling of an existing dominant
      anterior pseudopodium. In spite of these dramatic changes in pseudopodium
      behaviour, the underlying motility cycle of both mutants remains normal. The
      levels of F-actin in both mutant cell lines are significantly elevated with
      respect to the wild-type parental cells, suggesting a possible biochemical basis
      for these emphatic phenotypes.

PMID- 12211112
TI  - Diverse chemotactic responses of Dictyostelium discoideum amoebae in the
      developing (temporal) and stationary (spatial) concentration gradients of folic
      acid, cAMP, Ca(2+) and Mg(2+).
AB  - The responses of Dictyostelium discoideum amoebae to developing (temporal) and
      stationary (spatial) gradients of folic acid, cAMP, Ca(2+), and Mg(2+) were
      studied using the methods of computer-aided image analysis. The results presented
      demonstrate that the new type of experimental chambers used for the observation
      of single cells moving within the investigated gradients of chemoattractants
      permit time lapse recording of single amoebae and determination of the
      trajectories of moving cells. It was found that, besides folic acid and cAMP
      (natural chemoattractants for Dictyostelium discoideum amoebae), also
      extracellular Ca(2+) and Mg(2+) are potent inducers of these cells' chemotaxis,
      and the amoebae of D. discoideum can respond to various chemoattractants
      differently. In the positively developing gradients of folic acid, cAMP, Ca(2+),
      and Mg(2+) oriented locomotion of amoebae directed towards the higher
      concentration of the tested chemoattractants was observed. However, in the
      negatively developing (temporal) and stationary linear (spatial) gradients, the
      univocal chemotaxis of amoebae was recorded only in the case of the Mg(2+)
      concentration gradient. This demonstrates that amoebae can respond to both
      developing and stationary gradients, depending upon the nature of the
      chemoattractant. We also investigated the effects of chosen inhibitors of
      signalling pathways upon chemotaxis of D. discoideum amoebae in the positively
      developing (temporal) gradients of tested chemoattractants. Verapamil was found
      to abolish the chemotaxis of amoebae only in the Ca(2+) gradients. Pertussis
      toxin suppressed the chemotactic response of cells in the gradients of folic acid
      and cAMP but did not prevent chemotaxis in those of Ca(2+) and Mg(2+), while
      quinacrine inhibited chemotaxis in the gradients of folic acid, cAMP, and Ca(2+)
      but only slightly affected chemotaxis in the Mg(2+) gradient. None of the tested
      inhibitors causes inhibition of cell random movement, when applied in isotropic
      solution. Also EDTA and EGTA up to 50 mM concentration did not inhibit locomotion
      of amoebae in control isotropic solutions.

PMID- 12211113
TI  - Cytoplasmic dynein/dynactin mediates the assembly of aggresomes.
AB  - Aggresomes are pericentrosomal cytoplasmic structures into which aggregated,
      ubiquitinated, misfolded proteins are sequestered. Misfolded proteins accumulate
      in aggresomes when the capacity of the intracellular protein degradation
      machinery is exceeded. Previously, we demonstrated that an intact microtubule
      cytoskeleton is required for the aggresome formation [Johnston et al., 1998: J.
      Cell Biol. 143:1883-1898]. In this study, we have investigated the involvement of
      microtubules (MT) and MT motors in this process. Induction of aggresomes
      containing misfolded DeltaF508 CFTR is accompanied by a redistribution of the
      retrograde motor cytoplasmic dynein that colocalizes with aggresomal markers.
      Coexpression of the p50 (dynamitin) subunit of the dynein/dynactin complex
      prevents the formation of aggresomes, even in the presence of proteasome
      inhibitors. Using in vitro microtubule binding assays in conjunction with
      immunogold electron microscopy, our data demonstrate that misfolded DeltaF508
      CFTR associate with microtubules. We conclude that cytoplasmic dynein/dynactin is
      responsible for the directed transport of misfolded protein into aggresomes. The
      implications of these findings with respect to the pathogenesis of
      neurodegenerative disease are discussed.

PMID- 12211114
TI  - Characterization of nuclear betaII-tubulin in tumor cells: a possible novel
      target for taxol.
AB  - As the subunits of microtubules, alpha- and beta-tubulins have been thought to
      only exist in the cytoplasm where they are incorporated into microtubules.
      However, the beta(II) isotype of tubulin has recently been observed in the nuclei
      of rat kidney mesangial cells [Walss et al., 1999: Cell Motil. Cytoskeleton
      42:274-284]. In this study, we detected nuclear beta(II)-tubulin in rat C6 glioma
      cells, human T98G glioma cells, human MCF-7 breast carcinoma cells, human MDA-MB
      435 breast carcinoma cells, and human Hela cervix carcinoma cells. In addition,
      nuclear beta(II)-tubulin in these cells was found to exist as alphabeta(II)
      dimers instead of assembled microtubules and appeared to be particularly
      concentrated in the nucleoli. Several anti-tubulin drugs were used to treat C6
      cells to determine their influence on nuclear beta(II)-tubulin. Taxol, a tubulin
      drug with higher specificity for beta(II)-tubulin than for other beta-tubulin
      isotypes, irreversibly decreased nuclear beta(II) content in a concentration
      dependent manner in C6 cells. Meanwhile, cells were found to be apoptotic as was
      suggested by the presence of multiple micronuclei and DNA fragmentation. On the
      other hand, no depletion of nuclear beta(II)-tubulin was observed when C6 cells
      were incubated with colchicine or nocodazole, two anti-tubulin drugs with higher
      specificity for the alphabeta(IV) isotype, supporting the hypothesis that drugs
      with higher specificity for beta(II)-tubulin deplete nuclear beta(II)-tubulin.

PMID- 12211115
TI  - Cell migration and proliferation are not discriminatory factors in the in vitro
      sociologic behavior of bronchial epithelial cell lines.
AB  - A model of cellular cohesion has been developed, which permits the in vitro study
      of the spatial and temporal distribution of two human bronchial cell lines. The
      spatial distribution of cells in culture was characterized from videomicroscopic
      recordings and analyzed using an algorithmic program of cellular sociology based
      on the use of three geometrical models: Voronoi's partition, Delaunay's graph,
      the and minimum spanning tree (MST). The results obtained suggested that the
      manner of cellular cohesiveness could be used to differentiate between the
      organizational behaviors of the cell lines: non-invasive 16HBE14o- cells rapidly
      formed clusters with a cohesive organization, whereas invasive BZR cells remained
      isolated and were characterized by a non-cohesive organization. Videomicroscopic
      and image analysis techniques also demonstrated that cell migration and
      proliferation are not discriminatory factors for explaining differences in the
      spatial organizations of the two cell lines. We concluded that the random nature
      of cell movement combined with the cell adhesion capacity are determinant factors
      in cell cluster formation.

PMID- 12211117
TI  - Can clock drawing test help to differentiate between dementia of the Alzheimer's
      type and vascular dementia? A preliminary study.
AB  - OBJECTIVES: the purpose of this preliminary study was to determine if clock
      drawing performance may help to differentiate between dementia of the Alzheimer's
      type (DAT) and vascular dementia (VD) patients. METHODS: eighty-eight community
      dwelling outpatients were comprehensively evaluated and met DSM-IV criteria for
      DAT or VD. Cognitive evaluation included the Mini-Mental State Examination (MMSE)
      and the Cambridge Cognitive Examination (CAMCOG). CAMCOG derived clock drawings
      were blindly evaluated by the same investigator, according to Freedman's method
      for clock drawing, and a total score as well as subscores (contour, numbers,
      hands and center) were determined. RESULTS: There were no significant differences
      between DAT and VD patients in terms of demographic (age, gender, education) and
      cognitive (MMSE score, CAMCOG score) characteristics. On the average, the VD
      group showed slightly poorer performance on each of the clock drawing test (CDT)
      measures studied. With application of the Bonferroni correction, only Freedman's
      total score and hands subscore were statistically different between groups
      (p<0.003, p<0.004, respectively). Stepwise logistic regression analyses showed
      that the only significant variable was Freedman's total score (B=-0.273,
      p=0.005). Stepwise discriminant analysis identified Freedman's total score as the
      only significant predictor of diagnosis (Wilkes' lambda=0.903, p=0.003). This
      model correctly classified 65.9% overall into the respective DAT and VD groups.
      CONCLUSIONS: CDT scored according to a comprehensive technique may be of value in
      differentiating DAT from VD patients. We hypothesize that the classificatory
      ability of Freedman's method might be attributed to its presumed sensitivity to
      impaired executive functioning which is more pronounced in VD compared with DAT
      patients.

PMID- 12211116
TI  - Protein phosphorylation regulates actomyosin-driven vesicle movement in cell
      extracts isolated from the green algae, Chara corallina.
AB  - In Characean cells endoplasmic streaming stops upon membrane depolarization
      accompanied by Ca(2+) entry. We investigated the mechanism of this cessation of
      endoplasmic streaming by reconstituting the vesicle movement in vitro. In a
      living cell of Chara corallina, there are a number of vesicles moving along actin
      cables. Vesicles in the endoplasm squeezed out of the cell into a medium
      containing Mg-ATP showed directional movements under a dark field microscope.
      When the extracted endoplasm was treated with 20 nM okadaic acid, vesicles showed
      only movements like the Brownian motion. When it was treated with 50 nM
      staurosporine, directional movements of vesicles were activated. These movements
      were analyzed by image processing of videomicroscopic records. Vesicle movements
      along F-actin filaments were also observed by merging both images of the same
      field by dark field microscopy and fluorescence microscopy, indicating that
      myosin on the vesicle surface was responsible for vesicle movements. We also
      examined the effects of okadaic acid and staurosporine on in vitro sliding of F
      actin on Chara myosin. When Chara myosin was treated with 20 nM okadaic acid in
      the cell extract, the number of sliding F-actin filaments was greatly reduced. In
      contrast, it increased when Chara myosin was treated with 50 nM staurosporine. In
      addition, Chara myosin treated with protein kinase C greatly diminished its
      motility. These results suggest that inactivation of Chara myosin via its
      phosphorylation is responsible for cessation of endoplasmic streaming.

PMID- 12211118
TI  - Selective non-response to clinical assessment in the longitudinal study of aging:
      implications for estimating population levels of cognitive function and dementia.
AB  - OBJECTIVE: to identify the cognitive outcome of interviewed participants who did
      not progress to partake in clinical assessments in a longitudinal aging study.
      DESIGN: a retrospective study was conducted on participants who were interviewed
      but who did not complete the clinical assessment (including an extended cognitive
      assessment) at either Wave 1 or both Wave 1 and Wave 3 of the Australian
      Longitudinal Study of Ageing. A total of 1947 participants aged 70 and older
      commenced the study, 246 participants without clinical data at either or both
      Waves 1 and 3 were identified for the sub-sample followed-up retrospectively. The
      Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) was
      administered to informants and medical records were reviewed. RESULTS:
      participants who did not complete the clinical assessment at Wave 3 reported
      poorer health and had poorer cognitive function at Wave 1 independent of age and
      gender. Rates of possible dementia or cognitive decline were higher in the group
      who did not undertake the clinical assessment compared with both those who did
      the clinical assessment and with population data. CONCLUSION: selective non
      response to clinical assessment in a longitudinal aging study is associated with
      higher risk of cognitive decline and probable dementia. Longitudinal aging
      studies may underestimate rates of dementia and population levels of cognitive
      decline.

PMID- 12211119
TI  - Burnout and stress amongst old age psychiatrists.
AB  - OBJECTIVE: to investigate the relationship between work patterns, burnout and
      stress in consultant old age psychiatrists. METHODS: we sent a postal survey to
      all old age psychiatrists on the Faculty of Old Age Psychiatry, Royal College of
      Psychiatrists, list. Participants completed a workload questionnaire, the Stress
      Checklist and the Maslach Burnout Inventory during a specified week. RESULTS:
      burnout scores were unaffected by gender and team working, but old age
      psychiatrists scoring within the high burnout range were younger, scored highly
      on stress, spent less time on research, study and audit, and more time
      travelling. The whole group scored highly on emotional exhaustion. CONCLUSIONS:
      job plans should encourage research/study and audit, and cut down travelling. The
      finding related to age is not fully understood, but suggests consideration of
      support groups for new consultants and review of whether current training
      programmes adequately prepare people for work as a consultant.

PMID- 12211120
TI  - Factor structure of the Cornell Scale for Depression in Dementia among Japanese
      poststroke patients.
AB  - BACKGROUND: the present study reports on the first translation and use of the
      Cornell Scale for Depression in Dementia (CSDD) (Alexopoulos, Abrams, Young, &
      Shamoian, 1988) among poststroke patients (n = 101) in Japan. OBJECTIVES: the
      study had three main purposes: 1. To examine the factor structure of the CSDD
      among Japanese poststroke patients; 2. To compare this with the factor structure
      identified for Anglo-American Alzheimer's (AD) patients; and 3. To examine the
      prevalence and covariates of depressive symptoms among the Japanese stroke
      survivors. METHODS: poststroke patients and their caregivers (n = 202), at a
      random sample of neurological hospitals in western Japan, were interviewed using
      the study instruments. Data was also collected from patient charts. All subjects
      at each site who met the study criteria participated in the study. RESULTS: the
      four-factor solution for poststroke subjects was analogous to that found among AD
      patients with 2 main exceptions. In contrast to AD patients: 1. Physical
      complaints were unrelated to depressed mood in stroke patients; and 2. Agitation
      and psychosis loaded with depressed mood in stroke patients rather than as a
      separate unique factor as in AD patients. However, in the exploratory 5-factor
      model, agitation and suicidal ideation comprised a unique factor. Using standard
      cutoff scores for the CSDD, 58.2% of poststroke patients had scores suggesting
      possible depression. CSDD scores were not related to functional ability, or
      stroke characteristics such as aphasia or right or left-sided paralysis. However,
      scores were significantly higher among subjects < or = 2 years poststroke.
      Feelings of irritability, anxiety, sadness, and sleep problems were most
      prevalent. DISCUSSION: despite the prevalence of depressive symptoms, none of the
      subjects were currently receiving any mental health treatment. Findings suggest
      that symptoms differ by poststroke duration, which may necessitate different
      treatment approaches.

PMID- 12211121
TI  - Cross-cultural comparison of the Mini-Mental State examination in United Kingdom
      and United States participants with Alzheimer's disease.
AB  - OBJECTIVES: the relative difficulties of items on the Mini-Mental State
      Examination (MMSE) were compared in English-speaking Alzheimer's disease (AD)
      patients in the United States (US) and United Kingdom (UK). METHODS: participants
      were aged 75 and over, with a clinical diagnosis of AD according to standardized
      methods. Initial MMSE scores from an AD patient registry in the US (n = 401), and
      a field survey in the UK (n = 139) were compared. Item Characteristic Curve
      analysis (ICC) was used to calculate the relative difficulty of individual MMSE
      items, adjusted for the remaining MMSE items. Age, gender, education, and
      severity of disease were evaluated as possible confounders. RESULTS: UK
      participants found it relatively more difficult to name their county than US
      participants did to name their state. The relative difficulties of registration
      and recall, repeating a phrase, and following verbal directions also were
      significantly higher for the UK participants, even after adjustment for other
      factors. CONCLUSIONS: differences between the cohorts could be explained by
      translation artifacts in the test items or by cultural differences in the
      manifestation of AD. In this study, most, if not all differences can be explained
      by the former. ICC analysis can be used to develop tests that are functionally
      equivalent, a prerequisite for comparing dementia in different populations.

PMID- 12211122
TI  - The Geriatric Mental State Examination in the 21st century.
AB  - The Geriatric Mental State Examination (GMS) is now established as one of the
      most commonly used mental health assessments for older people. Its strengths lie
      in extensive validity studies, high inter-rater reliability, accessibility to
      trained raters, irrespective of professional background and its continual
      evolution and adaptation. Its computerisation, association with supplementary
      instruments and support by a diagnostic algorithm provides a comprehensive
      diagnostic system and syndrome profile for each subject. The instrument has been
      validated against most major diagnostic systems and has been used as outcome
      measures in intervention studies. It has been translated into numerous languages
      and validated as a diagnostic instrument in various cultures. Such studies have
      exposed weaknesses, including the over diagnoses of organic states in populations
      with poorly developed education. On-going studies continue to address these
      issues, providing a culture sensitive instrument enabling unique trans-cultural
      research in a relatively under-researched field.

PMID- 12211123
TI  - Personality traits and socio-epidemiological status of hospitalised elderly
      benzodiazepine users.
AB  - OBJECTIVE: to define personality traits and socio-epidemiological status of
      hospitalised elderly chronic benzodiazepine (BZD) users. METHODS: this case
      controlled study assessed psychological characteristics (using the Millon
      Clinical Multiaxial Inventory-MCMI-I) and socio-epidemiological status (sex, age,
      education, marital status and housing) in 40 hospitalised geriatric patients
      taking BZDs for at least 3 months and 40 non-users, excluding dementia. RESULTS:
      comparisons between groups: Compulsive personality pattern was more pronounced in
      the control group (p = 0.008). Severe personality pathology: a predisposition to
      borderline disorder was stronger among the BZD-users (p = 0.001). Clinical
      syndromes: anxiety, dysthymic disorder (p < 0.001) and tendency to alcohol
      dependence (p = 0.020) prevailed in the BZD-users. No severe syndromes were
      found. Widowed persons were more prevalent between the BZD-users (p = 0.03). All
      significant differences resulted from disparities between females. Predictors of
      BZD-use and clustering of traits: Dysthymic disorder was predictive of BZD-use
      (odds ratio (OR) 6.3 [95% confidence intervals (CI) 2.2-18.2]). It was strongly
      correlated with anxiety (r(s) = 0.93) and somatoform disorder (r(s) = 0.71).
      Dysthymic disorder and alcohol dependence predicted BZD-use in women (OR 15.3
      [CI: 2.4-95.7] and OR 9.1 [CI: 1.2-64.9], respectively). There were no specific
      predictors in men. CONCLUSIONS: chronic elderly BZD-users are typically widowed
      females with dysthymic disorder, anxiety, predisposition to alcohol dependence
      and borderline disorder. Before prescribing BZDs, it is important to recognize
      the nature of the elderly population at risk for BZD-use and to consider a
      broader-ranging therapeutic management of the predisposing personality traits.

PMID- 12211124
TI  - A confirmatory factor analysis of the 12-item General Health Questionnaire among
      older people.
AB  - BACKGROUND: the 12-item General Health Questionnaire (GHQ) is useful in measuring
      psychiatric morbidity in older people. Previous studies of its factor structure
      were often based on samples of young persons and on exploratory factor analysis
      techniques. The results varied from suggesting one to three factors. METHODS:
      this study involved 2123 participants aged over 60 and 7490 younger adults in a
      population-based survey in Britain. It compared the relative plausibility of
      several factor structures proposed by previous researchers, as indicated by the
      Akaike's Information Criterion and the Non-Normed Fit Index. Correlation between
      factors and internal consistency were examined. Mean subscale scores by
      demographic characteristics were analysed by ANOVA for the best-fit model.
      RESULTS: the 3-factor structure proposed by Graetz gave the best fit in both
      older and younger people. The properties of this model in older people were
      examined in details. The patterns of internal consistency and between-factor
      correlation were found satisfactory. Differences and similarities in subscale
      scores between demographic groups e.g. marital status, were presented.
      CONCLUSION: the 12-item General Health Questionnaire may measure three aspects of
      mental health, namely Anxiety and Depression, Social Dysfunction, and Loss of
      Confidence.

PMID- 12211125
TI  - The distribution of Mini-Mental State Examination scores in an older UK African
      Caribbean population compared to MRC CFA study norms.
AB  - OBJECTIVE: to describe normative data for the Mini-Mental State Examination
      (MMSE) in a UK African-Caribbean population and compare these with norms for
      white UK-born elders. DESIGN: a comparison of MMSE data from two cross-sectional
      surveys. METHOD: the MMSE had been administered to a community UK African
      Caribbean population and scores were compared to norms from the Medical Research
      Council Cognitive Function and Ageing Study (CFAS). MMSE data were analysed for
      248 African-Caribbean participants aged 55-75 and 5379 CFAS participants aged 65
      74, without visual or auditory problems. Distributions of scores were tabulated
      and error rates for individual items compared. RESULTS: Median MMSE scores were
      25 (interquartile range 22-27) for the whole African-Caribbean sample, 24 (22-27)
      for those aged 65-75 in the African-Caribbean sample, and 27 (25-29) for CFAS.
      Differences in error rates were specific to particular items: naming the season,
      serial seven subtraction, phrase repetition, three-stage command, and copying
      intersecting pentagons. These differences persisted when both samples were
      restricted to those with statutory duration of education, who were literate and
      who had worked in non-manual occupations. Normative data are displayed for MMSE
      scores in both groups. CONCLUSION: different distributions of MMSE scores between
      UK African-Caribbean and Caucasian groups can be principally explained by
      cultural bias in certain items. If the MMSE is to be administered to older
      African-Caribbean people, specific normative data should be referred to or else a
      culturally modified version of the instrument should be used.

PMID- 12211126
TI  - Just keep taking the tablets: adherence to antidepressant treatment in older
      people in primary care.
AB  - BACKGROUND: poor adherence to antidepressant medication may account for a
      significant proportion of treatment failures. Adherence levels and factors
      associated with adherence have not previously been studied in older people.
      OBJECTIVES: to report the prevalence and correlates of adherence to
      antidepressants in people > or = 65 years of age in a primary care setting.
      METHOD: sixty-seven patients currently being prescribed antidepressants from a
      single rural general practice were assessed using a range of questionnaires
      measuring adherence to antidepressants, severity of depression, specific health
      education about antidepressants, level of side-effects, insight, positive and
      negatives beliefs about medication in general and antidepressants in particular,
      level of intellectual functioning (past and present), a past history of recovery
      from depression, type of antidepressant, complexity of prescriptions, age and
      living arrangements. RESULTS: forty-five participants (67.2%) were fully
      adherent; seven (10.4%) mostly adherent, three (4.5%) adhered sometimes, three
      rarely and nine (13.4%) never. Backwards linear regression found that adherence
      increased with information given and cognitive impairment and decreased with
      concerns about taking antidepressants and severity of side-effects. CONCLUSIONS:
      non-adherence to antidepressant medication is a significant problem in older
      patients. Our study probably overestimated adherence as it was self-report, which
      usually overestimates adherence and the refusals are more likely to have been
      people not taking tablets but still found nearly one third of the patients were
      non-adherent. An intervention comprising education, eliciting and addressing
      specific concerns about antidepressant medication and using medication, which
      minimises side effects, may be helpful.

PMID- 12211127
TI  - Is mental health economics important in geriatric psychiatry in developing
      countries?
AB  - BACKGROUND: limited healthcare budgets and a seamless demand for resources
      suggests that a formula for allocating resources is needed. Economic evaluation
      can assist in developing this formula. METHOD: mental health economic studies
      (cost minimisation, cost-effectiveness, cost-utility, cost-benefit and cost of
      illness analysis) in geriatric psychiatry from developed and developed countries
      were examined along with all mental health economic studies in developed
      countries. RESULTS: there were no health economic studies in geriatric psychiatry
      from developing countries against a background of many such studies in developed
      countries. There were a greater number of health economic studies in other areas
      of psychiatry in developing countries. Several reasons for the paucity of such
      studies, the feasibility of undertaking these studies and their significance are
      discussed. CONCLUSION: mental health economic studies in geriatric psychiatry in
      developing countries are feasible, realistic and may well have an important part
      to play in the allocation of resources. Also, data sets necessary for such
      studies are emerging from many developing countries.

PMID- 12211128
TI  - Caregiver burden in mobile and non-mobile demented patients: a comparative study.
AB  - OBJECTIVES: to identify the impact of behavior disturbances on subjective burden
      of caregivers in demented patients attending day care services. METHODS: subjects
      were 379 primary caregivers of randomly sampled demented patients living at home,
      who attended geriatric day care programs. The caregiver burden of the mobile and
      non-mobile demented patients were measured using the Zarit Caregiver Burden
      Interview (ZBI). The Mini-Mental State Examination (MMSE) and the Personal Self
      Maintenance Scale (PSMS) were used to assess the patients' condition. The
      Troublesome Behavior Scale (TBS), originally developed in Japan, was used to
      assess the frequency of behavior disturbances exhibited by patients. RESULTS: the
      caregivers of the mobile demented patients reported greater caregiver burden
      compared to those of the non-mobile demented patients. The frequency of behavior
      disturbance was significantly higher in the mobile patients than the non-mobile
      patients. For the mobile patient caregivers, wandering, interfering, aggression
      and repetition were the predictors of caregiver burden. For the non-mobile
      patient caregivers, 'repeating same questions and/or clinging' was the only
      predictor of caregiver burden. CONCLUSION: the caregivers of the mobile demented
      patients reported higher burden due to the patients' behavior disturbance
      compared to those of the non-mobile patients. These findings indicate a need for
      further development of interventions to prevent behavior disturbances that are
      especially burdensome for caregivers.

PMID- 12211129
TI  - Relationship between depressive symptomatology and the subcortical brain syndrome
      in dementia.
AB  - OBJECTIVES: the aim of the present study was to elucidate a possible relationship
      between depressive symptomatology and regional brain symptomatology in demented
      patients. METHODS: 170 consecutive inpatients were studied. They suffered from
      Alzheimer's disease (103 patients), vascular dementia (48 patients), or
      frontotemporal dementia (19 patients). The patients underwent a neuropsychiatric
      investigation, which included assessments of (1) depression, and (2) regional
      brain symptomatology. Depressive symptomatology was assessed as presence of (a)
      depressed mood, and (b) anxiety. In the further statistical analysis, the
      presence of depressed mood and/or anxiety was also evaluated. The principle of
      the regional symptom analysis was the successive aggregation of observable
      symptom variables, leading to the final determination of four possible regional
      brain syndromes (frontal, subcortical, parietal and global), by way of the
      Stepwise comparative status analysis (STEP). The possible correlations between
      regional brain symptomatology and depressive symptomatology were analysed by
      means of (a) chi(2) statistics, and (b) a logistic regression analysis in which
      confounding factors were included (age, degree of dementia, duration). RESULTS:
      the subcortical syndrome correlated with depressed mood (chi(2), p = 0.002;
      logistic regression, p = 0.002). A negative correlation was noted between the
      parietal syndrome and depressed mood (p = 0.010 and p = 0.013, respectively). No
      other significant correlations between presence of regional brain syndrome and
      presence of depressive symptomatology could be seen. CONCLUSIONS: demented
      patients with a clinically established subcortical dysfunction appear to be more
      susceptible to depressive symptomatology. The results of this study also suggest
      that posterior brain dysfunction in dementia is not correlated with depressive
      symptomatology.

PMID- 12211130
TI  - A study of premorbid personality and behavioural and psychological symptoms of
      dementia in nursing home residents.
AB  - OBJECTIVE: to investigate the relationship between pre-morbid personality and
      behavioural and psychological symptoms of dementia (BPSD). METHODS: we studied 58
      subjects with dementia and depression and/or psychosis residing in 11 Sydney
      nursing homes cross-sectionally. Informal caregivers completed ratings of
      residents' pre-morbid personality on the NEP Five-Factor Inventory (NEO-FFI).
      Information on BPSD was obtained using the BEHAVE-AD. RESULTS: higher neuroticism
      was predictive of delusions; higher agreeableness of hallucinations,
      aggressiveness, affective disturbance and overall behavioural disturbance; and
      higher openness of affective disorder. CONCLUSION: our findings are inconsistent
      with previous research and clinical experience. Prospective studies are needed to
      clarify the association between personality and behavioural disturbance in
      dementia.

PMID- 12211131
TI  - Sunlight levels and behavioural disturbance in dementia.

PMID- 12211132
TI  - The psychogeriatric health care system in Germany.

PMID- 12211134
TI  - Management of Parkinson's disease: an evidence-based review.

PMID- 12211135
TI  - Anticholinergic therapies in the treatment of Parkinson's disease.

PMID- 12211136
TI  - Amantadine and other antiglutamate agents: management of Parkinson's disease.

PMID- 12211137
TI  - Levodopa: management of Parkinson's disease.

PMID- 12211138
TI  - MAO-B inhibitors for the treatment of Parkinson's disease.

PMID- 12211139
TI  - COMT inhibitors: management of Parkinson's disease.

PMID- 12211141
TI  - DA agonists -- ergot derivatives: bromocriptine: management of Parkinson's
      disease.

PMID- 12211142
TI  - DA agonists -- ergot derivatives: cabergoline: management of Parkinson's disease.

PMID- 12211143
TI  - DA agonists -- ergot derivatives: dihydroergocryptine (DHEC): management of
      Parkinson's disease.

PMID- 12211144
TI  - DA agonists -- ergot derivatives: lisuride: management of Parkinson's disease.

PMID- 12211145
TI  - DA agonists -- ergot derivatives: pergolide: management of Parkinson's disease.

PMID- 12211146
TI  - DA agonists -- non-ergot derivatives: apomorphine: management of Parkinson's
      disease.

PMID- 12211147
TI  - DA agonists -- non-ergot derivatives: piribedil: management of Parkinson's
      disease.

PMID- 12211148
TI  - DA agonists -- non-ergot derivatives: pramipexole: management of Parkinson's
      disease.

PMID- 12211149
TI  - DA agonists -- non-ergot derivatives: ropinirole: management of Parkinson's
      disease.

PMID- 12211150
TI  - Drugs to treat autonomic dysfunction in Parkinson's disease.

PMID- 12211151
TI  - Treatment of depression in idiopathic Parkinson's disease.

PMID- 12211152
TI  - Drugs to treat dementia and psychosis: management of Parkinson's disease.

PMID- 12211153
TI  - Surgical treatment for Parkinson's disease: deep brain surgery.

PMID- 12211154
TI  - Surgical treatment for Parkinson's disease: neural transplantation.

PMID- 12211155
TI  - Physical and occupational therapy in Parkinson's disease.

PMID- 12211156
TI  - Psychosocial counseling in Parkinson's disease.

PMID- 12211157
TI  - Speech therapy in Parkinson's disease.

PMID- 12211158
TI  - Proceedings of the Annual Meeting of the International Society for the Study of
      Women's Sexual Health. October 25-28, 2002. Boston, Massachusetts, USA.

PMID- 12211159
TI  - Retracted publication.

PMID- 12211160
TI  - Interhemispheric cooperation for familiar but not unfamiliar face processing.
AB  - Evidence for interhemispheric cooperation during language processing has been
      demonstrated for words, but not for meaningless pseudowords. Specifically,
      responses were found to be faster and more accurate when identical copies of a
      word were presented bilaterally to both hemispheres, relative to unilateral
      single presentations. This bilateral advantage for words seems to be a robust
      effect in normals. The present study addressed the question of whether the
      bilateral advantage is restricted to lexical material or whether it is a more
      global phenomenon occurring for meaningful material in general. Thirty healthy
      participants performed a familiarity decision in which one copy of familiar and
      unfamiliar faces was presented tachistoscopically to the right visual hemifield
      (RVF), the left visual hemifield (LVF) or simultaneously to both visual
      hemifields (bilateral condition, BVF). We obtained a highly significant
      familiarity by visual field interaction(P < 0.006) showing that only for familiar
      faces, a bilateral advantage was obtained. Unfamiliar face processing did not
      yield a bilateral advantage. We conclude that interhemispheric cooperation only
      occurs for meaningful material for which cortical representations can be assumed.

PMID- 12211161
TI  - Pathogenesis of HIV-associated lipodystrophy.

PMID- 12211162
TI  - Natural history and prevalence of HIV-associated lipodystrophy.

PMID- 12211163
TI  - Timing is everything.

PMID- 12211164
TI  - Keeping up in our swiftly changing field.

PMID- 12211165
TI  - HIV-related drug metabolism and cytochrome P450 enzymes.

PMID- 12211166
TI  - Report on the 13th International AIDS Conference.

PMID- 12211167
TI  - Antiretroviral rounds. Reason to be worried.

PMID- 12211168
TI  - Animal model for cerebral arteriovenous malformation (ref. Acta Neurochirurgica
      2000, 142; 1231-40.

PMID- 12211169
TI  - Platelet-derived growth factor A (pdgf-a) expression during zebrafish embryonic
      development.
AB  - Zebrafish pdgf-a gene was cloned and its expression pattern studied during
      zebrafish embryogenesis. Zebrafish pdgf-a mRNA was present at high levels in
      fertilized eggs as well as in all embryonic cells up to the end of gastrulation.
      Spatially restricted expression started after the onset of segmentation and was
      mainly localized in the developing pharyngeal arches. Transient expression was
      also detected in Kupffer's vesicle, a teleost-specific structure, and in lateral
      trunk and tail regions surrounding the neural keel, as well as areas of the
      developing pronephros.

PMID- 12211170
TI  - GFP expression in Hydra: lessons from the particle gun.
AB  - The cnidarian Hydra is an important model organism to study pattern formation and
      tem cell differentiation. In the past, however, it has been difficult to study
      gene function in Hydra because the animals have hot been accessible to gene
      transfection studies, we have now developed a method to transiently express GFP
      tagged proteins in Hydra using a green fluorescent protein (GFP) expression
      plasmid under the control of the Hydra actin promoter and a particle gun to
      introduce it into Hydra cell nuclei. We achieve strong transient GFP expression
      in a small but reproducible number of epithelial and interstitial cells.
      Implications for the use of this method to carry out single cell assays with GFP
      tagged Hydra proteins are discussed.

PMID- 12211171
TI  - Electronic poster presentations in BAPEN--a controlled evaluation.
AB  - INTRODUCTION: We sought to compare the quality of e-poster and traditional poster
      communications. METHODS: At the 2001 BAPEN congress, ten presenters were invited
      to supplement their poster by submitting its title and contents electronically.
      On projection, the submissions appeared as a poster. During chaired rounds,
      presenters 'talked to' the projection as if it were a traditional poster. They
      'clicked' onto individual tables or figures to enlarge to full screen. A further
      'click' returned the screen to poster format. Delegates attending two e-poster
      sessions, and a control group attending two simultaneous traditional poster
      rounds, responded to a questionnaire, on a scale 0--4, to statements which
      related: to the ability to (1) hear and (2) see well, (3) the posters'clarity and
      attractiveness, (4) whether the format of the session captured their interest and
      (5) encouraged discussion. Delegates also responded on how e-posters should be
      used in future meetings. Comparison was made using chi2 for trend. RESULTS:
      Questionnaires were returned from attendees at e-poster (27) and traditional (25)
      poster rounds. For all questions, the trend was in favour of e-posters with
      significant differences seen for 'seeing' (P= 0.009), 'interest capture' (P<
      0.007) and 'encouragement of discussion' (P<0.05). Thirty-two vs one delegates
      thought that e-posters should be used in future, 28 vs 4 delegates thought that e
      posters and traditional posters should be used together, but most(23 vs 8)
      thought that traditional posters should not be completely replaced. CONCLUSIONS:
      E-posters enable detailed search of a computer-based database of presentations,
      and viewing of the full content of all posters. Post-conference collaboration is
      enhanced by facilitating e-mail contact. E-posters should be used in tandem with
      traditional posters to improve the delivery of original communications.

PMID- 12211172
TI  - Report from the 2nd meeting on tracer Network for Metabolic Research.

PMID- 12211173
TI  - Bibliography. Current world literature. Drug allergy.

PMID- 12211174
TI  - Bibliography. Current world literature. Insect allergy.

PMID- 12211175
TI  - The anticlockwise twist.

PMID- 12211176
TI  - Practices in relation to nutritional care and support--report from the Council of
      Europe.
AB  - Disease-related undernutrition is significant in European hospitals but is seldom
      treated. In 1999, the Council of Europe decided to collect information regarding
      Nutrition programmes in hospitals and for this purpose a network consisting of
      national experts from 12 of the Partial Agreement member states was established.
      The aim was to review the current practice in Europe regarding hospital food
      provision, to highlight deficiencies and to issue recommendations in improve the
      nutritional care and support of hospitalised patients. The data collection
      regarding the nutritional care providers and their practices of nutritional care
      and support showed that the use of nutritional risk screening and assessment, and
      of nutritional support and counselling was sparse and inconsistent, and that the
      responsibilities in these contexts were unclear. Besides, the educational level
      with regard to nutritional care and support was limited at all levels. All
      patients have the right to expect that their nutritional needs will be fulfilled
      during a hospitalisation. Optimal supply of food is a prerequisite for an optimal
      effect of the specific treatment offered to patients. Hence, the responsibilities
      of staff categories and the hospital management with respect to procuring
      nutritional care and support should be clearly assigned. Also, a general
      improvement in the educational level of all staff groups is needed.

PMID- 12211177
TI  - Artificial nutrition: dilemmas in decision-making.
AB  - Artificial nutrition is a supportive medical therapy to attain pre-defined
      objectives, which should be adjusted to changing clinical situations. Optimal
      decision-making is based on the available scientific evidence blended with the
      science of probability and a spice of the art of uncertainty. Complex dilemmas in
      decision-making often occur given the paucity of solid scientific data to endorse
      precise indications and timing of prescription, whilst goals to be achieved may
      vary from clinical benefits to compassionate use. Hence, healthcare professionals
      must be aware and abide by the current norms of medical ethics, whereby eliciting
      and respecting patients' preferences is paramount. Patient-focused care implies:
      to respect patients' rights, to clearly inform and involve the patient in the
      decision-making process, to implement a therapeutic plan based on the best
      available care to suit patients' needs and informed options.

PMID- 12211178
TI  - Fetal MR imaging.

PMID- 12211179
TI  - Notched ureter sign.

PMID- 12211180
TI  - Comments on Diederich et al.: low dose CT: new tool for screening lung cancer.

PMID- 12211181
TI  - Serious deficiencies in numbers of medical physics experts in diagnostic
      radiology.

PMID- 12211183
TI  - Bibliography. Current world literature. Hemostasis/thrombosis.

PMID- 12211182
TI  - Sterilization issues in vCJD--towards a consensus: meeting between the Central
      Sterilizing Club and Hospital Infection Society. 12th September 2000.

PMID- 12211184
TI  - Gait analysis.

PMID- 12211185
TI  - Measuring functional abilities of patients with knee problems: rationale and
      construction of the DynaPort knee test.
AB  - We present the rationale and design of the DynaPort knee test. The test aims at
      measuring knee patients' functional abilities in an unobtrusive, user-friendly
      way. Test persons wear several belts around their trunk and legs. The belts
      contain accelerometers, the signals of which are stored in a recorder, embedded
      in one of the belts. The knee test consists of a set of 29 tasks related to
      activities of daily life ("test items"). Accelerometer signals are analyzed in
      terms of 30 "movement features" (accelerations, angles, durations, frequencies,
      and some dimensionless numbers). In data analysis, the beginning and end of each
      test item is marked by hand; otherwise, analysis is automatic. We compared 140
      knee patients with 32 healthy controls and found 541 of the 29 x 30=870 test item
      x movement feature combinations differed significantly between the two groups.
      From these 541 combinations the DynaPort knee score is calculated by the weighted
      averages of movement features per item, then weighted averages of items per
      cluster (locomotion, rising and descending, transfers, lifting and moving
      objects), and finally the average of the clusters. In an initial study the test
      retest reliability of the knee test proved high, and the test turned out to be
      sufficiently responsive (0.7 patients' standard deviations improvement after 24
      months). However, it remains difficult to interpret the scores in more meaningful
      terms than merely "better" or "worse." Extensive reliability studies in the
      future will further assess the validity of the test and provide more insight into
      the meaning of the scores. The DynaPort knee test may thus become an important
      instrument for evaluating patients'functional abilities in knee-related clinical
      practice and research.

PMID- 12211186
TI  - Radiofrequency energy induced heating of bovine capsular tissue: in vitro
      assessment of newly developed, temperature-controlled monopolar and bipolar
      radiofrequency electrodes.
AB  - This in vitro investigation characterized temperature changes associated with
      radiofrequency (RF) energy induced heating of bovine capsular tissue using newly
      developed, temperature-controlled monopolar (Vulcan RF system and Vulcan, TAC-S
      Electrothermal Probe) and bipolar (VAPR II RF system and VAPR TC RF electrode) RF
      systems and electrodes. Bovine capsular tissue samples were placed in a saline
      bath maintained at room temperature. Both RF generators were used at settings of
      75 degrees C and 40 W. The RF electrodes were placed in stationary positions on
      the tissue samples and activated for 1- to 10-s. A fluoroptic thermometry system
      was utilized to record temperatures at the RF electrode-tissue interface at 1-s
      intervals. The results indicated that the mean tissue temperatures for the
      monopolar RF electrode tended to be higher than those produced by the bipolar RF
      electrode, especially during the 2- to 10-s RF delivery time intervals (P<0.05).
      Notably, during the 2- to 10-s time intervals the monopolar RF electrode produced
      mean tissue temperatures that exceeded the set temperature of 75 degrees C (range
      of differences +1.2 to +15.7 degrees C highest mean temperature 90.7 degrees C).
      By comparison, the bipolar RF electrode maintained tissue temperatures relatively
      close to the set temperature(range of differences -3.2 to +2.7 degrees C; highest
      mean temperature 77.7 degrees C). These findings provide basic temperature
      profiles for the two new temperature-controlled RF devices.

PMID- 12211187
TI  - Original technique for the treatment of ligament-related genu recurvatum:
      preliminary results.

PMID- 12211188
TI  - Predictors of parental adjustment to children's epilepsy in rural India.
AB  - BACKGROUND: Negative societal attitudes towards disability affect the adjustment
      of parents when their child is diagnosed with epilepsy. Recent studies have
      suggested that parental and child outcomes, including adjustment, can be
      influenced by non-directed social support to mothers of children with disability.
      The objective of our study was to test the hypothesis that maternal satisfaction
      with social support, measured at the beginning of treatment, would predict
      parental adjustment to the child's epilepsy after 1 year of treatment. METHODS:
      We enrolled 46 mothers of children aged 6-18 years with epilepsy in the study. We
      measured social support using the modified Dunst family support scale, and
      parental adjustment using a locally validated instrument (S-PAM). Correlation was
      tested using a multiple linear regression model, allowing for confounding
      variables. RESULTS: Parental adjustment at outcome was positively independently
      correlated with satisfaction with social support at baseline,and negatively with
      severity of the child's epilepsy. The regression model explained 34% of the total
      variance. CONCLUSIONS: Taken together with evidence from previous studies, this
      finding supports the idea that helping parents to find more satisfaction within
      their (new or existing) social networks will promote adjustment to their child's
      disability.

PMID- 12211189
TI  - The meaning of a multimodal approach for children with ADHD: experiences of
      service professionals.
AB  - BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood mental
      disorder characterized by inattention, impulsiveness and overactivity. It is also
      characterized by heterogeneity and ambiguity. Effective intervention is
      influenced by these two factors. This pervasive disorder impacts various domains
      of functioning, including academics, peer relations, familial relationships and
      self-esteem. A confounding factor is the high rate of comorbidity with diagnoses
      such as learning disabilities, oppositional defiant disorder or conduct disorder.
      No one intervention has emerged as maximally effective across all symptoms and
      domains. Consequently, a multimodal approach is regarded as the favoured method
      of intervention. However, no clear definition of'multimodal' exists. METHOD: This
      study explored the meaning of multimodal from the perspective of professionals
      employed in a tertiary care hospital setting in which children with ADHD are
      assessed and treated. A qualitative design using a phenomenological approach
      allowed professionals to speak from their practice experiences. RESULTS AND
      CONCLUSION: Although no clear definition of multimodal emerged, professionals
      identified issues key to this approach and proposed a model for intervention.

PMID- 12211190
TI  - What families with children with brittle bones want to tell.
AB  - Osteogenesis imperfecta or brittle bone disease (BBD) is a most unusual disease
      and a limited number of people in the world are suffering from it. Most studies
      focus on the medical aspects of the disease and very little has been done with
      regard to the pedagogical and psycho-social aspects of the disease. This article
      is based on a questionnaire answered by 30 families, and interviews with 10
      families with children and adolescents with BBD, and the purpose is to survey the
      consequences of the disease in daily life. Although medical treatment is of
      utmost importance, it is necessary to regard also other aspects, as it is
      significant to have a holistic view of the child in his/her environment.

PMID- 12211191
TI  - Nightmares and anxiety in elementary-aged children: is there a relationship.
AB  - OBJECTIVE: To determine whether a relationship exists between children's anxiety
      level and nightmare occurrence. METHOD: A total of 60 kindergarten, second and
      fourth grade school children and their parents completed questionnaires assessing
      nightmare occurrence and anxiety. RESULTS: According to parental report, children
      who experience nightmares have significantly higher levels of anxiety than
      children who do not experience nightmares. The results also indicate a
      relationship between nightmare distress and trait anxiety. CONCLUSION: These
      findings suggest that anxiety issues should be considered in children who are
      experiencing nightmares.

PMID- 12211192
TI  - Psychological adjustment in children with end stage renal disease: the impact of
      maternal stress and coping.
AB  - OBJECTIVE: To explore maternal and child perspectives on children's adjustment in
      the context of paediatric renal disease, and maternal psychological variables
      that may account for variance in child and maternal ratings. METHODS: Forty-three
      children with end stage renal disease and their maternal caregivers completed the
      Strengths and Difficulties Questionnaire (SDQ). Mothers also reported on their
      own mental health, and the strategies they used to cope with their child's
      illness. The severity of the child's condition was rated independently by a renal
      clinician. RESULTS: Compared with normative data for the SDQ mothers reported
      their children to be at increased risk of psychological problems. However, the
      children themselves reported no more problems than a normative sample. Mothers'
      coping and mental health explained some of the variance in their ratings of the
      child's adjustment but were not predictive of the children's self-ratings.
      CONCLUSIONS: The results suggest that maternal factors may not explain the
      variability in children's adjustment to chronic illness, perhaps especially
      within the age range studied here. Practical implications of the data are also
      discussed. In particular, a systemic approach to paediatric liaison by
      psychologists is emphasized.

PMID- 12211193
TI  - Severe cold hemagglutinin disease (CHD) successfully treated with rituximab.

PMID- 12211194
TI  - Pharmacology of PEG-asparaginase in childhood acute lymphoblastic leukemia (ALL).

PMID- 12211195
TI  - Idiopathic thrombocytopenic purpura, Helicobacter pylori infection, and HLA class
      II alleles.

PMID- 12211196
TI  - ABO blood group also influences the von Willebrand factor (VWF) antigen level in
      heterozygous carriers of VWF null alleles, type 2N mutation Arg854GIn, and the
      missense mutation Cys2362Phe.

PMID- 12211197
TI  - Therapy-related MDS and AML in acute promyelocytic leukemia.

PMID- 12211198
TI  - Homozygous intragenic deletion of type I hexokinase gene causes lethal hemolytic
      anemia of the affected fetus.

PMID- 12211199
TI  - Congenital heart disease management in developing countries.

PMID- 12211200
TI  - Classification of a collection of malformed human hearts: practical experience in
      the use of sequential segmental analysis.
AB  - The inauguration of Sequential Segmental Analysis (SSA) a few decades ago
      provides basic conditions to establish a universally applicable classification
      system for cardiac malformations. To gain practical experience, we used this
      method to classify a collection of 292 congenitally malformed human hearts. Our
      aims were to determine advantages and problems of the SSA and to make
      recommendations for a better practical usability and documentation. SSA is an
      appropriate instrument for the description of complex cardiac malformations
      because it is a logical step-by-step approach based on the heart morphology. The
      method optimizes the diagnosis of different malformed hearts. However, there are
      some disadvantages of SSA concerning terminology, localization of simple septal
      defects and exact topographic description of heart structures. For these reasons,
      we recommend a graphic description of the malformed heart using symbols based on
      the SSA. The most important prerequisite for an interdisciplinary acceptable
      classification system of cardiac malformations is to include morphological as
      well as functional aspects of the hearts.

PMID- 12211201
TI  - Myocardial performance index combining systolic and diastolic myocardial
      performance in doxorubicin-treated patients and its correlation to conventional
      echo/Doppler indices.
AB  - This study was designed to evaluate the utility of myocardial performance index
      (MPI) in anthracycline cardiotoxicity. The MPI measures the ratio of total time
      spent in isovolumic activity (isovolumetric contraction time and isovolumetric
      relaxation time) to the ejection time, thus giving a global index combining
      systolic and diastolic myocardial performance. In this study, MPI was measured in
      35 doxorubicin-treated children (aged 108.5+/-55.31 months, 23 males and 12
      females) in sinus rhythm and 32 age-matched controls, and it was compared with
      conventional Doppler echocardiographic parameters. The isovolumetric contraction
      time was prolonged (38.37+/-24.43 vs 26.37+/-15.53, p <0.02) and ejection time
      was shortened (231.91 +/- 28.87 vs 256.21+/-19.55, p<0.001) in doxorubicin
      treated patients compared to that in normal children. The isovolumetric
      relaxation time did not show significant difference between patients and control
      group (60.11+/-10.92 vs 61.06+/-12.12, p>0.05). MPI was significantly increased
      in doxorubicin-treated patients compared with that in control groups (0.42+/-0.07
      vs 0.34+/-0.06, p<0.001), and significant correlation was observed between MPI
      and fractional shortening, ejection fraction, and left ventricular end diastolic
      and end systolic diameters (respectively, r = -0.508, p <0.002; r = -0.532,
      p<0.001; r = 0.467 p<0.005; r=0.606, p<0.001). Also, a weak correlation was found
      between MPI and duration of the disease and patient ages (r = 0.393, p < 0.02; r
      = 0.379; p < 0.02). However, there was no correlation between MPI and cumulative
      doxorubicin dose (r = 0.311, p > 0.05) and diastolic Doppler parameters in
      doxorubicin-treated patients. We think that MPI may be a useful parameter in
      monitoring left ventricular dysfunction in anthracyline-treated patients.

PMID- 12211202
TI  - Atrial septal defect with failure to thrive in infancy: hidden pulmonary vascular
      disease?
AB  - Atrial septal defects are usually asymptomatic, and are closed surgically or by a
      catheter implanted device in preschool age children. Rarely, they may cause
      symptoms in infancy, and management at this age is debated. We report our
      experience of six infants who underwent surgical closure, with variable outcomes.
      Five of these had significant extracardiac pathology. Our data suggest the need
      to exclude other causes of symptoms, both cardiac and non-cardiac. The question
      should be asked as to whether surgery is of benefit in these children, and
      particularly whether they may have underlying primary pulmonary vascular disease.

PMID- 12211203
TI  - Cardiac troponin T: its role in the diagnosis of clinically suspected acute
      myocarditis and chronic dilated cardiomyopathy in children.
AB  - This study was conducted to assess the use of the serum cardiac troponin T (cTnT)
      level as a noninvasive indicator to differentiate acute myocarditis and chronic
      dilated cardiomyopathy in pediatric patients. Myocarditis and dilated
      cardiomyopathy are clinically difficult to differentiate. Endomyocardial biopsy
      proved to be quite useful. However, the nature of the procedure--invasiveness,
      time-consuming, and limited sensitivity--caused some concerns, especially in
      pediatric patients. Hence, we attempted to find an alternative method that could
      give a prompt diagnosis of acute myocarditis. Twenty cases with clinically
      suspected myocarditis or dilated cardiomyopathy and a control group of 21 cases
      with moderate left-to-right shunt and congestive heart failure were recruited.
      History, physical examination, electrocardiogram, chest roentgenogram,
      echocardiogram, cTnT, creatine kinase MB isoenzyme (CK-MB mass), and/or
      endomyocardial biopsy were compared. The gold standard used to diagnose
      myocarditis is endomyocardial biopsy (Dallas criteria) and/or recovery from
      cardiovascular problems within 6 months of follow-up. Ten patients were diagnosed
      as having myocarditis (group 1) and 10 with chronic dilated cardiomyopathy (group
      2). The control group of 21 cases was designated as group 3. The median serum
      cTnT levels were 0.088 (0.04-3.11), 0.010 (0.010-0.990), and 0.010 (0.010-0.550)
      ng/ml in groups 1, 2, and 3, respectively. The mean CK-MB mass level for groups,
      1, 2, and 3 were 18.35 (7.14-70.00), 4.80 (0.54-108.00), and 2.26 (0.95-7.06)
      ng/ml. The study showed that both the cTnT and CK-MB mass levels were
      significantly higher in group 1 than either group 2 or group 3. Histopathology
      was studied in 9 cases. In 2 of 5 cases and in all 4 cases in group 1 and group 2
      histopathology was pathologically proved. Levels of cTnT and CK-MB were
      significantly higher for myocarditis than for dilated cardiomyopathy and left-to
      right shunt with CHF. Further study is needed to assess the optimum cTnT level
      for differentiating both conditions.

PMID- 12211204
TI  - Cardiac hydatic cyst causing cerebral emboli in a child.
AB  - Cardiac hydatic cyst is rarely encountered. In this article, a case of hydatid
      cyst localized in the left ventricle causing cerebral emboli is reported.

PMID- 12211205
TI  - Extreme pulsus alternans with P wave alternans in a child.
AB  - Pulsus alternans was observed in a child with left ventricular dysfunction
      secondary to systemic hypertension. The Echo-Doppler of supravalvular aorta and a
      simultaneous electrocardiographic trace (ECG) clearly demonstrated the mechanism
      of an apparent abrupt halving of pulse frequency compared with the ECG, similar
      to an electromechanical dissociation 2:1. Besides the extreme pulsus alternans, a
      P wave and a PP cycle length change were also observed. Both mechanical and
      electrical alternans disappeared with afterload reduction by nitroprusside
      treatment.

PMID- 12211206
TI  - Video-assisted cardioscopy for infectious endocarditis.
AB  - We successfully resected vegetation of infectious endocarditis in right
      ventricular outflow tract using a video-assisted cardioscopy without
      ventriculotomy. Video-assisted cardioscopy provided clear and precise
      visualization of vegetation on the anterior wall of right ventricular outflow.
      This technique is effective to visualize remote intra-cardiac structures, and to
      facilitate repairs, while avoiding the need for extended cardiac incisions.

PMID- 12211207
TI  - Minimal standards for electroencephalography in Canada.

PMID- 12211208
TI  - Theoretical framework for a dynamic cone-beam reconstruction algorithm based on a
      dynamic particle model.
AB  - Dynamic cone-beam reconstruction algorithms are required to reconstruct three
      dimensional (3D) image sequences on dynamic 3D CT combining multi-row two
      dimensional (2D) detectors and sub-second scanners. The speed-up of the rotating
      gantry allows one to improve the temporal resolution of the image sequence, but
      at the same time, it implies increase in the dose delivered during a given time
      period to keep constant the signal-to-noise ratio associated with each frame. The
      alternative solution proposed in this paper is to process data acquisition on
      several half-turns in order to reduce the dose delivered per rotation with the
      same signal-to-noise ratio. In order to compensate for time evolution and motion
      artefacts, we propose to use a dynamic particle model to describe the object
      evolution during the scan. In this article, we first introduce the dynamic
      particle model and the dynamic CT acquisition model. Then, we explain the
      principle of the proposed dynamic cone-beam reconstruction algorithm. Lastly, we
      present preliminary results on simulated data.

PMID- 12211209
TI  - Multichannel algorithm for fast 3D reconstruction.
AB  - Some recent medical imaging applications such as functional imaging (PET and
      SPECT) or interventional imaging (CT fluoroscopy) involve increasing amounts of
      data. In order to reduce the image reconstruction time, we develop a new fast 3D
      reconstruction algorithm based on a divide and conquer approach. The proposed
      multichannel algorithm performs an indirect frequential subband decomposition of
      the image f to be reconstructed (f = sigma fj) through the filtering of the
      projections Rf. The subband images fj are reconstructed on a downsampled grid
      without information suppression. In order to reduce the computation time, we do
      not backproject the null filtered projections and we downsample the number of
      projections according to the Shannon conditions associated with the subband
      image. Our algorithm is based on filtering and backprojection operators. Using
      the same algorithms for these basic operators, our approach is three and a half
      times faster than a classical FBP algorithm for a 2D image 512 x 512 and six
      times faster for a 3D image 32 x 512 x 512.

PMID- 12211211
TI  - A novel nanoporous graphitic composite.
AB  - A novel nanoporous composite containing micrographitic carbon layers is
      synthesized by preliminarily expanding the interlayer of an oxidized product of
      graphite using surfactant, followed by Si bridging/pillaring, and carbonization.

PMID- 12211212
TI  - LET dependence of lethality in Arabidopsis thaliana irradiated by heavy ions.
AB  - To clarify the effect of heavy ions in plants, dry seeds of Arabidopsis were
      irradiated with carbon, neon, and argon ions with various linear energy transfer
      (LET) values. The relative biological effectiveness (RBE) for lethality peaked at
      LET values over 350 keV/microns for neon and argon ions. This LET giving the peak
      RBE was higher than the LET of 100-200 keV/microns which was reported to have a
      maximum RBE for other types of cells, such as mammalian cells. Furthermore,
      sterility showed a higher RBE at an LET of 354 keV/microns with neon ions than
      that at an LET of 113 keV/microns with carbon ions. Lethality and sterility are
      both considered to be caused by damage to DNA. The results indicate that the LET
      having a maximum of RBE for lethality is higher in Arabidopsis seeds than in
      other unicellular systems. The most likely explanation for this shift of LET is
      that the DNA in dry seeds has a different chemical environment and/or hydration
      state than the DNA in cells in culture.

PMID- 12211214
TI  - [12S rRNA, cytochrome b and MDR1 gene DNA sequence and phylogenetic evolution of
      Muntiacus (M. muntjak, M. reevesi, M. crinifros)].
AB  - In the paper, 784 bp-DNA fragmensts of 12S rRNA and cytochrome b gene on
      Mitochondrial DNA and 728 bp-DNA fragments of MDR1 (multidrug resistance) gene
      from Muntiacus (M. muntjak, M. reevesi, M. crinifrons) were amplified and
      sequenced, while their phylogenetic relationships and classification were
      analysed. The molecular phylogenetic trees were constructed based on these
      combined DNA sequences, the results suggested that DIST is 0.042 between M.
      crinifrons and M. muntjak; DIST is 0.047 between M. crinifrons and M. reevesi;
      DIST is 0.055 between M. muntjak and M. reevesi, counted according to the
      evolution speed of 2.5% per million year, the divergent time between M.
      crinifrons and M. muntjak is 1.68 million year; the divergent time between M.
      crinifrons and M. reevesi is 1.88 million year; the divergent time between M.
      muntjak and M. reevesi is 2.2 million year; The conclusion is that the M.
      crinifrons and M. reevesi were diverged from an ancestor analogied with M.
      muntjak, M. nuntjak is the oldest species, M. crinifrons and M. reevesi are newer
      ones.

PMID- 12211213
TI  - A phase I trial of weekly gemcitabine and subcutaneous interferon alpha in
      patients with refractory renal cell carcinoma.
AB  - INTRODUCTION: Recombinant human interferon-a2b (rHuIFN-alpha2b) and Interleukin-2
      have limited effectiveness in the treatment of metastatic renal cell carcinoma
      (MRCC). Gemcitabine (Gemzar) is also reported to have activity against MRCC, and
      recent in vitro, in nude mice xenografts, and human data suggests increased
      activity of gemcitabine (Gemzar) when combined with IFN-alpha2b. PURPOSE: A phase
      I clinical trial utilizing gemcitabine (Gemzar and rHuIFN-alpha2b was conducted
      in patients with metastatic renal cell carcinoma. METHODS: Treatment consisted
      of: gemcitabine (Gemzar) 600 mg/m2 I.V. weekly and rHuIFN-alpha2b 1.0 MU/m2 (dose
      level A) or 3.0MU/m2 S.C. (dose level B) three times a week for 6 weeks with a 2
      weeks rest period. RESULTS: Thirteen patients were entered into the trial and
      were evaluated. Dose limiting toxicity was predominantly hematologic, and was
      seen at dose level B. This included grade 3 anemia (1 patient), neutropenia (1
      patient), and nausea (1 patient) and grade 4 neutropenia (1 patient). The maximal
      tolerated dose was gemcitabine (Gemzar) 600 mg/m2 I.V. weekly and rHuIFN-alpha2b
      1.0 MU/m2 three times a week. CONCLUSION: This combination of gemcitabine
      (Gemzar) and rHuIFN-alpha2b has significant hematologic toxicity despite low
      doses of each agent. Further investigation of this combination using this
      schedule is not recommended.

PMID- 12211215
TI  - Potential mouse tumor model for pre-clinical testing of mage-specific breast
      cancer vaccines.
AB  - Currently, there is a lack of suitable pre-clinical mouse models for testing and
      optimization of experimental cancer vaccines. Here, in situ developed mammary
      tumors of MMTV-v-Ha-ras and MMTV-c-myc transgenic mice and normal mammary, liver,
      spleen, and testis were screened for expression of tumor-associated antigens
      (TAA) Mage-b1/2/3 by reverse-transcriptase polymerase chain reaction (RT-PCR) and
      Southern blot hybridization. Mage-b1/2/3 are homologues of the human TAA MAGE
      B1/2/3. Expression of these human MAGE genes has been found in tumors of various
      histological types, including breast cancer. Mage-specific RT-PCR products (using
      primers that amplify all three Mage-b1/2/3) were detected in mammary tumors of
      the MMTV-v-Ha-ras and MMTV-c-myc transgenic mice and in testis, but not in other
      normal tissues. RT-PCR products obtained from the mammary tumors (using primers
      that amplify the complete protein-encoding region of Mage-b1/2/3) were cloned and
      sequenced, and appeared to be most homologous with Mage-b3. Comparison of the
      Mage-b3 gene in mammary tumors and normal tissues suggest that somatic mutations
      did not occur in the Mage-b3 gene of the ras- and myc-induced mammary tumors. In
      addition, no differences were found between the Mage-b3 cDNA of testis, the only
      normal tissue that expresses Mage-b3, and Mage-b3 in genomic DNA of normal
      kidney, where Mage-b3 is silent. The MMTV-v-Ha-ras and MMTV-c-myc transgenic mice
      of this study are the first immune competent mouse models with in situ developed
      mammary tumors in which the expression of Mage-b3 TAA has been demonstrated. This
      makes them potentially suitable as a mouse model for pre-clinical testing of Mage
      specific cancer vaccines in vivo.

PMID- 12211216
TI  - Galantamine pharmacokinetics, safety, and tolerability profiles are similar in
      healthy Caucasian and Japanese subjects.
AB  - The aim of this study was to compare the pharmacokinetics of galantamine in
      healthy Japanese and Caucasian subjects and assess the safety and tolerability of
      galantamine in both ethnic groups. Parallel groups of healthy Japanese (n = 13; 6
      males and 7 females)and Caucasian (n = 12; 6 males and 6 females) subjects
      matched for weight and age received single oral doses of galantamine 4 mg, or
      galantamine 8 mg, or placebo in a double-blind, three-way crossover trial
      according to a randomized dosing schedule. Concentrations of galantamine and
      norgalantamine were determined in plasma and urine samples taken up to 48 and 24
      hours after dosing, respectively. Safety and tolerability were monitored
      throughout the trial by recording adverse events, laboratory tests, and
      cardiovascular parameters. The mean plasma concentration-time profiles of
      galantamine were very similar after single doses of galantamine (4 and 8 mg), and
      there was an approximate dose proportionality of galantamine pharmacokinetic
      parameters in both Caucasian and Japanese ethnic groups. The mean (+/- SD)
      pharmacokinetic parameters in the two ethnic groups did not show any clinically
      relevant differences. The ratios for the area under the plasma-concentration
      curve from time zero to infinity (AUC)0-infinity) in Japanese:Caucasian subjects
      with 4 and 8 mg doses were 103% (90% confidence interval [CII = 92-116) and 107%
      (90% CI = 94-121), respectively. Ratios for maximum plasma concentration (Cmax)
      values were 107% (90% CI= 90-127) and 108% (90% CI= 95-123), respectively. These
      ratios and associated 90% CIs were within the 80% to 125% range limit of
      bioequivalence. Analysis of variance (ANOVA) showed that these ratio values
      demonstrated no statistically significant difference between the two ethnic
      groups. There was no overt difference in the adverse event profile in Japanese
      subjects compared with Caucasian subjects. There were no serious adverse events,
      and no subjects discontinued from the study because of adverse events. No
      consistent or clinically relevant pattern of blood chemistry, hematology, or
      cardiovascular changes was seen. These results suggest that the pharmacokinetic
      profiles of galantamine after single-dose administration are not statistically
      significantly different between Caucasian and Japanese groups. Galantamine was
      well tolerated. The safety and tolerability of galantamine were very similar in
      the two ethnic groups.

PMID- 12211217
TI  - Pharmacokinetic evaluation of the possible interaction between selected
      concomitant medications and orlistat at steady state in healthy subjects.
AB  - To investigate the influence of orlistat on the pharmacokinetics of selected
      concomitant medications (amitriptyline, atorvastatin, cyclosporine, losartan,
      metformin, phentermine, and sibutramine) at or within two-fold of therapeutic
      doses, open-label, multiple-dose (for 6 or 7 days), randomized, two-period
      (except for cyclosporine, for which a three-way crossover design was used)
      crossover studies were performed in healthy volunteers ages 18 to 65 years, with
      a body mass index between 18 and 30 kg/m2. At steady state, blood samples were
      taken for measuring plasma concentrations of interacting drugs and/or active
      metabolites. Subjects were also evaluated for adverse events, vital signs, and
      clinical and laboratory safety. Treatments were compared for AUC0-24, Cmax, tmax,
      and t1/2 of selected concomitant medications (parent drugs and/or active
      metabolites). ANOVA was performed to assess the significance of the carry-over
      effect and provide the variance estimate for the 90% confidence intervals (CIs).
      With the exception of cyclosporine, whose absorption was reduced by approximately
      one-third, the results of the statistical analysis demonstrated equivalencefor
      the two primary parameters for all drugs studied: ratios of the log-transformed
      means for both AUC and Cmax were close to 1.00, with 90% CIs contained entirely
      within the bioequivalence region of 0.80 to 1.25; there were no clinically
      significant differences in t1/2 and tmax. There was a higher incidence of adverse
      events under treatment B (selective concomitant medications and orlistat) than
      under treatment A (selective concomitant medications alone); most of this
      difference was due to expected gastrointestinal adverse events known to occur
      with orlistat. Other adverse events were sporadic and unremarkable. All adverse
      events were either mild or moderate in intensity. There were no clinically
      relevant changes in vital signs or laboratory values. In conclusion, except for
      cyclosporine, there was no effect of orlistat on the pharmacokinetics of
      selective concomitant medications when these drugs were taken concomitantly with
      orlistat.

PMID- 12211218
TI  - Pharmacokinetic and pharmacodynamic differences between ocular and nasal
      instillation of carteolol on intraocular pressure and heart rate in Japanese men
      with high CYP2D6 activity.
AB  - Sublingual administration of carteolol or instillation into one eye reduces
      intraocular pressure (IOP) in both eyes. This suggests that carteolol absorbed
      systemically can reduce IOP and that the extra-ophthalmic route (e.g., the nasal
      route) can be an alternative method of drug administration. The authors compared
      the differences between ocular and nasal instillation relating to the
      pharmacokinetic and pharmacodynamic effects of a carteolol-ophthalmic solution on
      IOP and heart rate (HR) in a randomized, double-blind, crossover, placebo
      controlled design in 11 healthyyoung extensive metabolizers for CYP2D6. The tmax,
      Cmax, and AUC0-t of carteolol (0.8 mg) instilled into the nostril were
      significantly higher than those into the eye (p < 0.05): tmax (h) = 0.25 (0.17
      5.0),1.0 (0.17-5.0) (median value with range in the parenthesis, ocular vs.
      nasal); Cmax (ng/ml) = 1.33 +/- 1.57, 2.29 +/- 2.09; and AUC0-t (ng x h/ml) =
      9.36 +/- 2.04, 21.13 +/- 1.58 (geometric mean +/- SD, ocular vs. nasal). The
      reduction of IOP after ocular instillation persisted significantly longer than
      that of nasal instillation (p < 0.05). The HR was significantly reduced after
      both ocular and nasal instillation (p < 0.05), although there were no significant
      differences between them. In conclusion, ocular instillation of a carteolol
      ophthalmic solution has advantages over nasal instillation in controlling IOP and
      the potential to decrease adverse reactions due to lower plasma concentrations.

PMID- 12211219
TI  - Celecoxib does not affect the antiplatelet activity of aspirin in healthy
      volunteers.
AB  - Celecoxib is a novel cyclooxygenase-2-specific inhibitor for the management of
      acute pain, primary dysmenorrhea, and the signs and symptoms of arthritis. This
      double-blind, placebo-controlled study in 16 healthy volunteers evaluated whether
      celecoxib alters the effect of concomitant aspirin on platelet function.
      Volunteers received celecoxib (400 mg/day) or placebo for 4 days. On day 5, they
      also received a single 325 mg dose of aspirin with either 200 mg celecoxib or
      placebo. Thromboxane and platelet aggregation response to adenosine 5'
      diphosphate (ADP), collagen, and arachidonic acid were measured before the first
      dose of celecoxib or placebo (baseline) and before dosing and 2 and 8 hours post
      dose on day 5. There was no significant difference in thromboxane inhibition
      between the two groups (percent inhibition: placebo 99.4%, celecoxib 99.0%; p =
      0.555). There was also no significant difference in the effect of aspirin on
      platelet aggregation due to ADP, collagen, or arachidonic acid between the
      groups. Therefore, these data indicate that celecoxib does not alter the effects
      of aspirin on platelet function.

PMID- 12211220
TI  - Which studies of therapy merit credence? Vitamin E and estrogen therapy as
      cautionary examples.
AB  - A vast and continuously growing amount of material on drugs exists in the
      literature to read and evaluate. Frequently, the papers and their recommendations
      are conflicting and contradictory. Readers are faced with the dilemma of deciding
      what to believe. The need for evidence-based medicine as a foundation for optimal
      clinical research and patient care requires application of the best scientific
      methods. Various methods are discussed. Generally, the most powerful method to
      test a clinical hypothesis is the randomized, controlled clinical trial. By
      contrast, epidemiology/observation studies have certain inherent weaknesses that
      can lead to erroneous conclusions. The examples of estrogen therapy in
      postmenopausal women and of vitamin E therapy to reduce cardiovascular risk are
      discussed extensively to provide historical perspective and to demonstrate
      erroneous conclusions reached using epidemiology/observation studies. The
      sociology of journal publication is briefly described, and an attempt is made to
      assess who benefits and who is harmed when leading medical journals publish
      erroneous results. Types of bias and confounding issues leading to errors are
      discussed, and the need is emphasized for publication of rigorous studies after
      careful evaluation by editors to avoid repetition of past mistakes and to ensure
      publication of correct medical information.

PMID- 12211221
TI  - A review of the pharmacologic and pharmacokinetic aspects of rosuvastatin.
AB  - Rosuvastatin is a new HMG-CoA reductase inhibitor with unique pharmacologic and
      pharmacokinetic properties. It has additional HMG-CoA reductase enzyme-binding
      interactions that cause tighter binding, has substantial active transport into
      hepatocytes, and has the lowest IC50 for sterol synthesis in hepatocytes.
      Rosuvastatin 10 mg and 80 mg dosages have superior low-density lipoprotein (LDL)
      cholesterol-lowering efficacy as compared to atorvastatin 10 mg and 80 mg.
      Rosuvastatin 10 mghas also been shown to have superior LDL reductions to 20 mg of
      both simvastatin and pravastatin. This agent can raise high-density lipoprotein
      (HDL) 8% to 12% and lower triglycerides by 10% to 35%. Rosuvastatin is a
      hydrophilic agent with poor penetration in extrahepatic tissue such as human
      umbilical vein endothelial cells and fibroblasts. It also has a low potential for
      cytochrome P450 drug interactions and can be dosed in the morning or night. In
      conclusion, rosuvastatin is an agent with molecular alterations that provide it
      with unique pharmacologic and phannacokinetic effects. As such, it is a novel and
      unique HMG-CoA reductase inhibitor for the treatment of hyperlipidemia.

PMID- 12211223
TI  - Coriolus versicolor: a medicinal mushroom with promising immunotherapeutic
      values.
AB  - Coriolus versicolor (CV) is a medicinal mushroom widely prescribed for the
      prophylaxis and treatment of cancer and infection in China. In recent years, it
      has been extensively demonstrated both preclinically and clinically that aqueous
      extracts obtained from CV display a wide array of biological activities,
      including stimulatory effects on different immune cells and inhibition of cancer
      growth. The growing popularity of aqueous CV extracts as an adjunct medical
      modality to conventional cancer therapies has generated substantial commercial
      interest in developing these extracts into consistent and efficacious oral
      proprietary products. While very limited information is available on the
      physical, chemical, and pharmacodynamic properties of the active principles
      present in these extracts, there has been sufficient scientific evidence to
      support the feasibility of developing at least some of these constituents into an
      evidence-based immunodulatory agent. In this article, the background, traditional
      usage, pharmacological activities, clinical effects, adverse reactions, active
      constituents, and regulatory aspects of CV are reviewed. Presented also in this
      review are the current uses and administration, potential drug interactions, and
      contraindication of aqueous extracts prepared from CV.

PMID- 12211222
TI  - Evaluation of highly bound drugs: interspecies, intersubject, and related
      comparisons.
AB  - Free (unbound) drug is generally the pharmacologically relevant parameter for
      drug exposure. Thus, comparisons among species, among individuals, and in other
      situations such as cell culture or drug metabolism experiments in vitro should be
      based on free drug. Although the traditional focus has been on the absolute value
      for free drug, the applications for the data in this study are primarily
      comparative. Therefore, the authors evaluated direct dialysis of one plasma
      sample versus another. At equilibrium, the total concentration of valproate in
      human plasma was 3-fold higher than in rat plasma. The total concentration of
      monoacetyl dapsone was 10-fold higher in human plasma than in rat plasma and 18
      fold higher in human plasma than in dog plasma. These results confirm predictions
      derived from conventional dialysis of each plasma sample separately versus
      buffer. These data can be interpreted directly, without interspecies correction
      factors for binding, especially for the most important cases--drugs that are
      highly protein-bound.

PMID- 12211224
TI  - Effects of celecoxib and diclofenac on blood pressure, renal function, and
      vasoactive prostanoids in young and elderly subjects.
AB  - Cyclooxygenase (COX) inhibitors are among the most widely used drugs, especially
      in the elderly. It has been claimed that the new COX-2 inhibitors offer
      advantages in terms of drug safety. To test this hypothesis, the authors compared
      in a double-blind, randomized trial the effects of celecoxib (200 mg bid) and
      diclofenac (75 mg bid) on blood pressure and renal function in two groups (each n
      = 12) of young (mean age = 32 years) and elderly (mean age = 68 years)
      normotensive subjects. Changes from baseline in the 24-hour blood pressure
      profiles, parameters of the renin-angiotensin-aldosterone system, inulin
      clearance, urinary marker proteins, and eicosanoid excretion were monitored
      during the treatment period of 2 weeks. Comparison between celecoxib and
      diclofenac showed no significant difference in minor alterations of blood
      pressure. During daytime, there was a trend to elevation of mean arterial blood
      pressure (mmHg) by celecoxib in the elderly of 2.8 (95 % confidence interval [CI)
      = -2.5 to 8.2) in comparison with the young subjects of -1.3 (95% CI= -3.7 to
      1.0); there was also a trend to elevation of mean arterial blood pressure by
      diclofenac in the elderly of 4.1 (95% CI= -1.2 to 9.4) in comparison with the
      young subjects of 0.4 (95% CI= -2.4 to 3.2). In both populations, the authors
      found no significant drug effects on the parameters of the renin-angiotensin
      aldosterone system, inulin clearance, and urinary marker proteins. As expected,
      diclofenac reduced excretion of allprostanoids, whereas celecoxib did not affect
      production of TxB2 and its metabolites. Neither in young nor in elderly
      normotensive subjects were blood pressure and renal function significantly
      affected by a short-term treatment with standard doses of celecoxib and
      diclofenac. Therefore, normal aging appears not to represent a special risk
      factor in therapy with these two agents.

PMID- 12211226
TI  - Data on IVF clinics show wide variation in success rate.

PMID- 12211225
TI  - Novel formulations of cetrorelix acetate in healthy men: pharmacodynamic effects
      and noncompartmental pharmacokinetics.
AB  - The objective of this study was to investigate the effects on the
      pharmacodynamics and noncompartmental pharmacokinetics after weekly subcutaneous
      administration of novel formulations of cetrorelix acetate in healthy men. In a
      randomized parallel-group study, single subcutaneous doses of cetrorelix acetate
      (concentration: 2.5 mg peptide base/ml) dissolved in aqueous gluconic acid
      (CET/glu, dose: 5 or 10 mg peptide base) or in water (CET/wat, dose: 10 mg
      peptide base) were given to 36 subjects once weekly in the morning for 4 weeks.
      Cetrorelix plasma, serum testosterone, luteinizing hormone, andfollicle
      stimulating hormone concentrations were monitored after each administration for 1
      week, with extensive profiling after the first and fourth administration.
      Cetrorelix plasma concentrations were analyzed by radioimmunoassay and serum
      hormone concentrations by enzyme immunoassays. At least half-maximum testosterone
      suppression started with all treatments within less than 1 day. Deepest and
      longest testosterone suppression was achieved by 10 mg CET/glu. Duration of
      atleasthalf-maximum suppression was after the first dose median of 82 hours and
      after the fourth dose median of 122 hours, respectively. Substantial suppression
      was also evidentfor luteinizing hormone (LH) and, to a lesser extent, forfollicle
      stimulating hormone (FSH). On average, Cmax was nearly doubled after single and
      multiple doses, and AUC(tau) was increased by about 50% after single doses and
      about 30% after multiple doses of 10 mg CET/glu as compared to 10 mg CET/wat. For
      tmax and t1/2, no significant differences were found between formulations. It was
      concluded that testosterone suppression increased with weekly subcutaneous
      administrations of 10 mg CET/glu. Compared to CET/wat, bioavailability and
      duration of suppression were increased with CET/glu.

PMID- 12211227
TI  - Commentary: Systematic reviewers face challenges from varied study designs.

PMID- 12211228
TI  - Commentary: A UK primary care perspective on treating acne.

PMID- 12211229
TI  - Social insurance--the right way forward for health care in the United Kingdom?
      Against.

PMID- 12211230
TI  - Peer review of statistics in medical research. Suggested solution may partly
      solve other problem.

PMID- 12211231
TI  - Peer review of statistics in medical research. Reviewers' contributions should be
      thoughtful, constructive, and encouraging.

PMID- 12211232
TI  - Peer review of statistics in medical research. Rationale for requiring power
      calculations is needed.

PMID- 12211233
TI  - Peer review of statistics in medical research. Reporting power calculations is
      important.

PMID- 12211234
TI  - Trends in HIV, gonorrhoea, and syphilis. Sexual health services in general
      practice can be improved.

PMID- 12211235
TI  - Selection of medical students. Sheffield University has developed an outreach
      programme.

PMID- 12211237
TI  - On Hippocrates. Either help or do not harm the patient.

PMID- 12211238
TI  - Does the presence of ideomotor apraxia affect the prognosis of functional
      recovery in a woman who has had a stroke?

PMID- 12211239
TI  - Can a comprehensive lymphedema management program decrease limb size and reduce
      the incidence of infection in a woman with postmastectomy lymphedema?

PMID- 12211240
TI  - Mantophasmatodea now in South Africa.

PMID- 12211241
TI  - Mycobacterium leprae and demyelination.

PMID- 12211242
TI  - The ups and downs of global research centers.

PMID- 12211243
TI  - Human reproductive cloning.

PMID- 12211244
TI  - Quaestio disputata: when does quality of life count? A response to Gilbert
      Meilaender.

PMID- 12211245
TI  - The fivefold root of an ethics of surgery.
AB  - Surgical ethics have generally been framed as general medical ethics applied to
      surgical contexts. This model is helpful, but may miss some of the special
      features of the surgical process and relationship. It is suggested in this paper
      that there are five categories of experience and relationship which are
      especially important in surgery--rescue, proximity, ordeal, aftermath, and
      presence. The sense of rescue, the feeling of relational proximity, the ordeal
      and aftermath of surgery are things which the patient experiences. Understanding
      these experiences allow surgeons to understand what may be asked of them in an
      ethical sense. Recognition of the reality and validity of each category in the
      surgical process highlights the importance of presence, the acts by which the
      surgeon demonstrates that he is present to the patient throughout the surgical
      process and its aftermath. While the teaching of communication skills may never
      compensate for insensitivity, the ideal of presence as virtue and duty can be
      taught by precept and example.

PMID- 12211246
TI  - Abortion and neonaticide: ethics, practice, and policy in four nations.
AB  - Abortion, particularly later-term abortion, and neonaticide, selective non
      treatment of newborns, are feasible management strategies for fetuses or newborns
      diagnosed with severe abnormalities. However, policy varies considerably among
      developed nations. This article examines abortion and neonatal policy in four
      nations: Israel, the US, the UK and Denmark. In Israel, late-term abortion is
      permitted while non-treatment of newborns is prohibited. In the US, on the other
      hand, later-term abortion is severely restricted, while treatment to newborns may
      be withdrawn. Policy in the UK and Denmark bridges some of these gaps with
      liberal abortion and neonatal policy. Disparate policy within and between nations
      creates practical and ethical difficulties. Practice diverges from policy as many
      practitioners find it difficult to adhere to official policy. Ethically, it is
      difficult to entirely justify perinatal policy in these nations. In each nation,
      there are elements of ethically sound policy, while other aspects cannot be
      defended. Ethical policy hinges on two underlying normative issues: the question
      of fetal/newborn status and the morality of killing and letting die. While each
      issue has been the subject of extensive debate, there are firm ethical norms that
      should serve as the basis for coherent and consistent perinatal policy. These
      include 1) a grant of full moral and legal status to the newborn but only partial
      moral and legal status to the late-term fetus 2) a general prohibition against
      feticide unless to save the life of the mother or prevent the birth of a fetus
      facing certain death or severe pain or suffering and 3) a general endorsement of
      neonaticide subject to a parent's assessment of the newborn's interest broadly
      defined to consider physical harm as well as social, psychological and or
      financial harm to related third parties. Policies in each of the nations surveyed
      diverging from these norms should be the subject of public discourse and, where
      possible, legislative reform.

PMID- 12211247
TI  - Competence and paternalism.
AB  - Some bioethicists have argued in favor of a sliding scale notion of competence,
      paternalistically requiring greater competence in relation to more significant
      risk. I argue against a sliding scale notion, taking issue with the positions of
      Allen E. Buchanan and Dan W. Brock, Ian Wilkes, and Joel Feinberg. Rejecting
      arguments that a sliding scale is supported by legal cases, by ordinary usage,
      and by fallible judgments about competence, I argue in favor of greater evidence
      of competence when risk is greater. Two clinical cases are examined, both
      involving amputation, to show that my fixed concept of competence, with a
      requirement of clearer evidence of competence when risk is high, better accounts
      for good moral decisions in bioethics.

PMID- 12211248
TI  - On cloning human beings.
AB  - The purpose of this paper is to show that arguments for and against cloning fail
      to make their case because of one or both of the following reasons: 1) they take
      for granted customary beliefs and assumptions that are far from being
      unquestionable; 2) they tend to ignore the context in which human cloning is
      developed. I will analyze some of the assumptions underlying the main arguments
      that have been offered for and against cloning. Once these assumptions are
      critically analyzed, arguments both rejecting and supporting human cloning seem
      to lose weight. I will first briefly present the main arguments that have been
      proposed against cloning and I will argue that they fail to establish their case.
      In the next section I will evaluate some of the positive arguments that have been
      offered supporting such technology. This analysis will show that the case for
      cloning also fails. Finally, I will maintain that because critics and especially
      supporters of this technology neglect the context in which human cloning is
      developed and might be implemented, their arguments are far from compelling.

PMID- 12211250
TI  - A response to Walter Glannon.

PMID- 12211249
TI  - Identity, prudential concern, and extended lives.
AB  - Recent advances in human genetics suggest that it may become possible to
      genetically manipulate telomerase and embryonic stem cells to alter the
      mechanisms of aging and extend the human life span. But a life span significantly
      longer than the present norm would be undesirable because it would severely
      weaken the connections between past- and future-oriented mental states and turn
      the psychological grounds for personal identity and prudential concern for our
      future selves. In addition, the collective effects of longer lives might lower
      the quality of life for all people. These two problems provide reasons against
      genetic manipulation of cells to alter the length of the human life span.

PMID- 12211251
TI  - Reply to Harris.

PMID- 12211252
TI  - The effect of space flight on human cellular immunity.
AB  - T-lymphocyte responsiveness to mitogens is depressed by an average of 56% in
      humans (129 subjects) tested during and after space flight. Although there is not
      yet conclusive evidence of a clinical significance of the test, it is clear that
      factors of space flight like stress, closed environment and cosmic radiation may
      affect immune responsiveness. The data obtained from space crews may be compared
      to the depression seen in subjects undergoing heavy physical stress of head down
      tilt bedrest. Recently, delayed hypersensitivity [correction of hypersensivity]
      response was tested on crews of the US space shuttle and of the orbital station
      MIR by means of a commercially available "skin test". Again, the response was
      lower in 14 of the 15 subjects tested. In two cases, a strong in flight
      depression could be related to heavy physical and psychological stress
      experienced in flight. The data available today are not sufficient to draw
      conclusions on the hazard of infectious diseases during and after space flight.
      Although the changes observed never harmed the health of astronauts,
      immunological changes must be seriously investigated and understood in view of
      long-duration flights on space stations in an Earth orbit and to other planets
      like Mars and the Moon.

PMID- 12211253
TI  - Role of the sympathetic nervous system in the generation of one-minute wave in
      body fluid volume during upright standing.
AB  - In clarifying the role of sympathetic nerve outflow to the muscles in the genesis
      of one-minute waves in body fluid volume, power spectral analysis of muscle
      sympathetic nerve activity (MSNA) was performed. MSNA was recorded by
      microneurography in an upright standing position simultaneously with the
      measurements of body circumference, venous pressure at the dorsum pedis veins,
      intrathoracic fluid volume, soleus EMG, and calf fluid volume. Subjects were
      seven healthy male volunteers aged 18 to 32 years. Spectral analysis revealed the
      one-minute oscillation in MSNA as well as in other variables. Cross spectral
      analysis between the soleus EMG and each variable revealed a phase order of the
      one-minute oscillations. It was as follows: 1) an increase in calf fluid volume;
      2) a decrease in intrathoracic fluid volume; 3) an increase in venous pressure at
      the dorsum pedis veins; 4) an increase in the soleus EMG activation; 5) an
      activation of MSNA; 6) a decrease in calf fluid volume; and 7) an increase in
      intrathoracic fluid volume. It is concluded that sympathetic nerve activity as
      well as cardiovascular variables have a cyclic rhythm with a duration of one
      minute to maintain hemodynamic homeostasis in humans in an upright standing
      position.

PMID- 12211254
TI  - [One hundred years' history of public health activities in Korea].
AB  - In a dictionary of epidemiology, recently edited by John Last, public health was
      defined as one of the efforts organized by society to protest, promote, and
      restore the peoples' health. It is the combination of sciences, skills, and
      beliefs that is directed to the maintenance and improvement of the health of all
      the people through collective or social action. In most countries, the efforts to
      protect, promote, and restore the peoples' health are mostly organized by the
      government, and therefore, the history of public health in the respective
      countries is closely related to the state of government and its administrative
      structures. In this article, the history of public health activities in Korea
      during the last 100 years has been reviewed in four consecutive time periods from
      the end of Li Dynasty till now. The public health during the first some 50 years
      from 1897 when the Dae Han Empire began to 1945 when the Japanese colonial period
      ended can be characterized by enforcement of personal and environmental hygiene
      by the police. In those days, communicable disease control was the main purpose
      of such public health measures. Second phase of Korean public health from 1945 to
      the time of military coup in 1961 is characterized by enactment of various public
      health laws and the related public health practices. Major health related laws
      are communicable disease control law, environmental hygiene act, industrial
      safety and health law, and so on. Important public health practice in this time
      period was family planning. Third phase of public health history from 1962 to
      1992 can be recorded as the time when the actual public health practices were
      fully developed. Because of well established health center activities throughout
      the country, basic public health services were provided together with primary
      medical care services to the people in rural areas. Since 1993, two civilian
      governments have been trying to change the concept of their health administration
      from providing public health services to improve welfare of the whole population.
      Emphasis was put on health promotion, and for this, the government enacted a
      health promotion law. Based on this law, even special funds for various health
      promotion activities are now available by taxing on tobacco sales.

PMID- 12211256
TI  - Teaching a college course on children and death: a 13-year report.

PMID- 12211257
TI  - Medicare program; prospective payment system for long-term care hospitals:
      implementation and FY 2003 rates. Final rule.
AB  - This final rule establishes a prospective payment system for Medicare payment of
      inpatient hospital services furnished by long-term care hospitals (LTCHs)
      described in section 1886(d)(1)(B)(iv) of the Social Security Act (the Act). This
      final rule implements section 123 of the Medicare, Medicaid, and SCHIP [State
      Children's Health Insurance Program] Balanced Budget Refinement Act of 1999
      (BBRA) and section 307(b) of the Medicare, Medicaid, and SCHIP Benefits
      Improvement and Protection Act of 2000 (BIPA). Section 123 of the BBRA directs
      the Secretary to develop and implement a prospective payment system for LTCHs.
      The prospective payment system described in this final rule replaces the
      reasonable cost-based payment system under which LTCHs are currently paid.

PMID- 12211258
TI  - Health insurance flexibility and accountability initiative: opportunities and
      issues for states.

PMID- 12211259
TI  - Factors affecting nonmedical participants' allocation of scarce medical
      resources.
AB  - This study was designed to determine the factors that affect nonmedical
      participants' judgments in constructing a ranked waiting list for kidney patients
      requiring dialysis. Participants (N=167) were given a questionnaire that provided
      minimal demographic data about 16 hypothetical patients. Participants were
      requested to rank patients in order of priority for treatment. Each participant's
      personal demographic details were also obtained. Patients differed on four
      dimensions: gender, income, alcohol consumption, and religious beliefs, yielding
      a 2x2x2x2 design. The participants favoured for treatment included females over
      males, "poor" over "rich," nondrinkers over drinkers, and Christians over
      atheists. Results are discussed in terms of establishing democratic criteria and
      informing medical personnel on explicit factors which may affect their decision
      making, thus guarding against biases in judgment.

PMID- 12211260
TI  - Last rights: the ethics of research on the dead.
AB  - People have strong views about being the subjects of research after their deaths.
      Should these views be given any weight and, if so, how much? How could we find
      out what the views are and what should we do if we cannot? This paper defends the
      idea of posthumous interests and discusses the significance of those interests
      for research ethics. It argues that we can be guided by a symmetry between the
      interests of living and dead people and uses posthumous privacy as an example. It
      also claims that the weight of those interests might not decline even over long
      periods of time. The arguments have important implications for the ethics of
      (amongst others) biomedical, archaeological, anthropological, historical, and
      sociological research.

PMID- 12211261
TI  - Euthanasia in the Netherlands: the state of the legal debate.

PMID- 12211262
TI  - Informed consent ten years later: the impact of Reibl v. Hughes.
AB  - In 1980 the Supreme Court of Canada introduced major doctrinal changes in the law
      of informed consent in its decision in Reibl v. Hughes. This article assesses the
      significance of that decision by examining its impact in a number of areas. Based
      on an analysis of 117 cases since Reibl, the article concludes that the decision
      has had very little impact on the frequency and severity of malpractice claims.
      Reibl has also had little impact on legal developments in other areas of health
      law or in jurisdictions outside Canada, and its effect on medical practice
      remains unclear. The article concludes that the true significance of Reibl may
      lie in its symbolic importance as reflecting a fundamental change in the doctor
      patient relationship and the power and authority underlying that relationship.

PMID- 12211263
TI  - Pharmacogenetics: ethical issues and policy options.
AB  - Pharmacogenetics offers the prospect of an era of safer and more effective drugs,
      as well as more individualized use of drug therapies. Before the benefits of
      pharmacogenetics can be realized, the ethical issues that arise in research and
      clinical application of pharmacogenetic technologies must be addressed. The
      ethical issues raised by pharmacogenetics can be addressed under six headings:
      (1) regulatory oversight, (2) confidentiality and privacy, (3) informed consent,
      (4) availability of drugs, (5) access, and (6) clinicians' changing
      responsibilities in the era of pharmacogenetic medicine. We analyze each of these
      categories of ethical issues and provide policy approaches for addressing them.

PMID- 12211264
TI  - Searching across boundaries: national information resource on ethics and human
      genetics.

PMID- 12211265
TI  - Paying for kidneys: the case against prohibition.
AB  - We argue that healthy people should be allowed to sell one of their kidneys while
      they are alive--that the current prohibition on payment for kidneys ought to be
      overturned. Our argument has three parts. First, we argue that the moral basis
      for the current policy on live kidney donations and on the sale of other kinds of
      tissue implies that we ought to legalize the sale of kidneys. Second, we address
      the objection that the sale of kidneys is intrinsically wrong because it violates
      the Kantian duty of respect for humanity. Third, we address a range of
      consequentialist objections based on the idea that kidney sales will be
      exploitative. Throughout the paper, we argue only that it ought to be legal for
      an individual to receive payment for a kidney. We do not argue that it ought to
      be legal for an individual to buy a kidney.

PMID- 12211266
TI  - Public policy and the sale of human organs.
AB  - Gill and Sade, in the preceding article in this issue of the Kennedy Institute of
      Ethics Journal, argue that living individuals should be free from legal
      constraints against selling their organs. The present commentary responds to
      several of their claims. It explains why an analogy between kidneys and blood
      fails; why, as a matter of public policy, we prohibit the sale of human solid
      organs, yet allow the sale of blood; and why their attack on Kant's putative
      argument against the sale of human body parts is misplaced. Finally, it rejects
      the claim that the state is entitled to interfere with the actions of individuals
      only if such actions would harm others. We draw certain lines grounded in what
      Rawls has termed "public reason" beyond which we do not give effect to the
      autonomous self-regarding decisions of individuals. Public resistance to the sale
      of human body parts, no matter how voluntary or well informed, is grounded in the
      conviction that such a practice would diminish human dignity and our sense of
      solidarity. A system of organ donation, in contrast, conveys our respect for
      persons and honors our common humanity.

PMID- 12211267
TI  - Reasonable magic and the nature of alchemy: Jewish reflections on human embryonic
      stem cell research.
AB  - The controversy about research on human embryonic stem cells both divides and
      defines us, raising fundamental ethical and religious questions about the nature
      of the self and the limits of science. This article uses Jewish sources to
      articulate fundamental concerns about the forbiddenness of knowledge in general
      and of knowledge thought of as magical creation. Alchemy, and the turning of
      elements into gold and into substances for longevity, and magic used for the
      creation of living beings was at stake in various Talmudic texts. Since
      contemporary discourse calls regenerative science magical, and makes claims about
      its restorative power, careful reflection on when magic is forbidden and when it
      is responsible allows a novel understanding of ethical questions in stem cell
      research.

PMID- 12211268
TI  - Some initial reflections on NBAC.

PMID- 12211269
TI  - Comment on the muromics "garden path".

PMID- 12211270
TI  - "Outbreak of hind limb paralysis in young CFW Swiss Webster mice".

PMID- 12211271
TI  - Evolution: the founding principle of animal models of human disease.

PMID- 12211272
TI  - Factors affecting oogenesis in the South African clawed frog (Xenopus laevis).
AB  - Xenopus laevis, commonly known as the South African Clawed frog, is a hardy
      adaptable species that is relatively easy to maintain as a laboratory animal.
      Gametogenesis in wild Xenopus laevis is continuous and under ideal conditions,
      reproduction can occur year round. This unique aspect of amphibian reproduction
      offers an advantage over mammalian model systems: the eggs and oocytes collected
      from laboratory maintained Xenopus laevis provide an abundant and readily
      obtainable supply of material for cellular and biological research. However, many
      investigators report that laboratory Xenopus laevis go through periods of
      unexplained inefficient or complete failure of oocyte production or the
      production of poor quality oocytes. This results in experimental delays,
      inability to reproduce data, and ultimately the use of more animals. There is a
      lack of evidenced based information regarding the housing conditions that are
      necessary to optimize the health and fecundity of this species in captivity, but
      studies of wild Xenopus laevis have shown that temperature, age of the female,
      and nutrition are of key importance. The objective of this report is to review
      oogenesis with a special emphasis on these factors as they pertain to laboratory
      Xenopus laevis maintained for the purpose of providing a steady supply of eggs
      and oocytes. Harvesting methods and other experimental techniques that affect the
      quality of eggs and oocytes are also discussed.

PMID- 12211273
TI  - Evaluation of sensitivity and specificity of a Mycoplasma haemomuris-specific
      polymerase chain reaction test.
AB  - BACKGROUND AND PURPOSE: Mycoplasma haemomuris, a small pleomorphic bacterium
      parasitic of red blood cells, often causes chronic and subclinical infection of
      rodents. Mycoplasma haemomuris is uncultivable, and a serologic testing method is
      not readily available. The purpose of the study reported here was to develop a
      sensitive and specific polymerase chain reaction (PCR) test for detection of M.
      haemomuris in blood samples. METHODS: On the basis of the regions of the M.
      haemomuris 16S rRNA gene most divergent from corresponding regions of related
      bacteria, M. haemomuris-specific primers were designed so that these primers
      could selectively amplify M. haemomuris DNA. A PCR test was performed, using
      blood samples from BALB/c mice infected with M. haemomuris strains TR 8564, TR
      8563, and TR 8556. RESULTS: Use of the PCR test enabled detection of M.
      haemomuris DNA in a minimum of 0.0001 microl of infected mouse blood. The test
      also was specific for M. haemomuris and did not amplify closely related species,
      such as M. haemofelis, M. haemosuis, M. orale, or Anaplasma marginale.
      CONCLUSION: This method is sensitive and specific for detection of M. haemomuris.

PMID- 12211274
TI  - Evaluation of a spontaneous canine model of immunoglobulin E-mediated food
      hypersensitivity: dynamic changes in serum and fecal allergen-specific
      immunoglobulin E values relative to dietary change.
AB  - The purpose of the pilot study reported here was to evaluate serum and fecal
      total and allergen-specific immunoglobulin E (IgE) responses to dietary change in
      five Maltese x beagle dogs with suspected food hypersensitivity, compared with
      those of five clinically normal dogs. Clinical parameters (pruritus, otitis, and
      diarrhea) improved in the Maltese x beagle dogs during feeding of a novel diet,
      and signs were exacerbated by oral allergen provocation. Relative concentrations
      of serum and fecal wheat-, corn-, and milk-specific IgE were determined by use of
      an ELISA. The onset of clinical signs of disease was accompanied by an increase
      in serum allergen-specific IgE concentrations. In contrast, changes in clinical
      signs of disease or allergen-specific IgE values were not seen in the control
      group undergoing the same regimen. Total serum IgE concentration was measured by
      use of the ELISA, and comparison with known quantities of a monoclonal IgE
      allowed absolute values to be reported. Values were high in the Maltese x beagle
      colony (7 to 34 microg/ml), compared with those in the control dogs (0.7 to 6
      microg/ml). Total serum and total fecal IgE concentrations did not change in
      either group during the study. Although allergen-specific IgE was detected in the
      feces of both groups, significant interassay variability made interpretation of
      the results difficult. The authors concluded that these Maltese x beagle dogs
      satisfied the currently recognized clinical criteria for the diagnosis of canine
      food hypersensitivity. Furthermore, the clinical and serologic responses seen in
      these dogs in response to oral allergen provocation suggest that this may be a
      useful model for the study of spontaneous food hypersensitivity.

PMID- 12211275
TI  - Characterization of lymphocyte subsets in the bronchiolar lymph nodes of BALB/c
      mice infected with cilia-associated respiratory bacillus.
AB  - Cilia-associated respiratory (CAR) bacillus is an unclassified, gram-negative,
      extracellular bacterium that causes chronic respiratory tract disease in rodents.
      Infected mice develop microscopic lesions characterized by a primary lymphocytic
      response followed by macrophage and neutrophilic infiltration. To characterize
      the lymphocytic subsets that respond to CAR bacillus infection, BALB/c mice were
      inoculated with 10(5) CAR bacillus bacteria. At seven weeks after inoculation,
      mice were euthanized and the tracheobronchiolar and hilar lymph nodes were
      collected and stained for cell surface markers to T cells (CD3, CD4, and CD8), B
      cells (B220, CD5), natural killer (NK) cells (pan-NK) and intracellular
      interleukin 10 (IL-10) and interferon-gamma (IFN-gamma). Flow cytometric analysis
      of lymph nodes from CAR bacillus-infected mice revealed 11% increase in frequency
      of B cells (R220+), 12% increase in the frequency of double-negative (CD4-CD8
      CD3+) T cells, and slight increase in the B-1 subset of B cells (B220+CD5+).
      There was no change in the frequency of NK cells. The CAR bacillus-infected mice
      had an overall decrease in the frequency of T cells. Intracellular cytokine
      staining revealed distinct populations of T cells producing IL-10 and IFN-gamma,
      and IL-10 production from B cells; NK cells were not a substantial source of IFN
      gamma. To our knowledge, this is the first characterization of lymphocytic
      responses and suggestion that B cells and double-negative T cells may be
      principally responsible for the lesions associated with CAR bacillus infection.

PMID- 12211276
TI  - Soft tissue movement and stress shielding do not affect bone ingrowth in the bone
      conduction chamber.
AB  - A variety of bone chambers are used in orthopedic research to study bone and
      tissue ingrowth in small and large animals. If different bone chambers are placed
      in one species, differences in bone ingrowth are observed. For instance, bone
      ingrowth in the bone conduction chamber (BCC) is high, but is low or absent in
      the repeated sampling bone chamber (RSBC). This difference may be explained by
      the design and fixation of these chambers. It is known that stress shielding and
      micromovement can influence bone formation. The objective of the study reported
      here was to determine whether stress shielding or soft tissue movement affected
      bone ingrowth in the BCC in the goat. Two types of caps were made, with fixation
      similar to that of the fixation plate of the RSBC. By placing the caps over the
      BCCs and fixating the caps directly to the tibial bone, the effect of stress
      shielding was studied. One cap was in direct contact with the bone chamber
      underneath, the other cap did not touch the chamber. This difference was used to
      observe whether movement of the soft tissue on top of the chamber and cap would
      affect bone ingrowth. Each limb received one control chamber without a cap and a
      chamber with a cap, either with or without contacting the BCC, yielding four
      implants per goat. After 12 weeks, bone and total tissue ingrowths were measured.
      Bone ingrowth was seen in 38 of 40 chambers. Total tissue and bone ingrowths were
      comparable between control chambers and BCCs with a cap, irrespective of type.
      Neither stress shielding, nor lack of movement of soft tissue affected bone
      ingrowth. Other factors in the design of the chambers were responsible for the
      difference in bone ingrowth between the BCC and the RSBC.

PMID- 12211277
TI  - Adoptive transfer of BALb/c mouse splenocytes reduces lesion severity and induces
      intestinal pathophysiologic changes in the Mycobacterium avium Subspecies
      paratuberculosis beige/scid mouse model.
AB  - Successful immune reconstitution would enhance resistance of beige/scid mice to
      chronic infection with Mycobacterium avium subspecies paratuberculosis, but may
      cause damage to intestinal tissue. Therefore, we investigated the effect of
      adoptive transfer of BALB/c mouse splenocytes on lesion severity and intestinal
      physiology in beige/scid mice infected with M. paratuberculosis. Mice were
      inoculated intraperitoneally (i.p.) with M. paratuberculosis, and two weeks later
      were inoculated i.p. with viable spleen cells from immune-competent BALB/c mice.
      Mice were necropsied 12 weeks after infection when engraftment of lymphocytes,
      clinical disease, pathologic lesions, and intestinal electrophysiologic
      parameters were evaluated. Lymphocytes were rare in control beige/scid mice not
      inoculated with spleen cells. In contrast, high numbers of CD4+, CD8+, and B220+
      lymphocytes were detected in the spleen of all beige/scid mice (n = 24)
      inoculated with spleen cells, indicating that adoptive transfer resulted in
      successful engraftment of donor lymphocytes (immune reconstitution). Immune
      reconstitution of M. paratuberculosis-infected beige/ scid mice significantly
      reduced the severity of clinical disease and pathologic lesions, and numbers of
      bacteria in the liver. However, intestinal electrophysiologic parameters studied
      in vitro indicated that intestinal tissues from reconstituted beige/scid mice had
      reduced short-circuit current responses (due to reduced ion secretion) following
      electrical, glucose, and forskolin stimulation. These abnormal responses
      suggested that neural or epithelial cells in the intestine were damaged. We
      conclude that successful immune reconstitution of beige/scid mice enhance their
      resistance to M. paratuberculosis infection, but may cause pathophysiologic
      changes associated with intestinal inflammation.

PMID- 12211278
TI  - Optimal equilibration conditions for practical vitrification of two-cell mouse
      embryos.
AB  - The objective of the study reported here was to elucidate the optimal
      equilibration conditions for carrying out vitrification of two-cell mouse
      embryos, using a solution containing 2M dimethyl sulfoxide, 1M acetamide, and 3M
      propylene glycol (DAP213) as a cryoprotectant. Embryos were subjected to an
      equilibration process under 20 conditions of a combination of different
      temperatures (10 to 37 degrees C) and times (5 to 90 sec), and viability of the
      embryos was assessed by the rate of development into blastocysts and into live
      fetuses. As a result, these rates of development into blastocysts did not differ
      from those for unfrozen embryos. The rate of development of frozen-thawed embryos
      into live fetuses under conditions of 30 sec. at 20 degrees C, which was selected
      as having by highest operability, was 55.2%, comparable to the value (65.0%) for
      unfrozen embryos. Thus, the optimal equilibration condition for vitrification of
      two-cell mouse embryos, using DAP213 solution, was 30 sec at 20 degrees C, under
      which embryo viability was maximized, and this equilibration process was
      considered useful as a practical two-cell embryo freezing process in the
      vitrification method.

PMID- 12211279
TI  - Detection of rodent Helicobacter spp. by use of fluorogenic nuclease polymerase
      chain reaction assays.
AB  - Polymerase chain reaction (PCR) analysis is the standard method for detection of
      Helicobacter spp. infections in laboratory rodents, with H. hepaticus, H. bilis,
      and H. typhlonius considered primary pathogens. Fluorogenic nuclease PCR assays
      that detect all known rodent Helicobacter spp., or that specifically detect H.
      hepaticus, H. bilis, or H. typhlonius were developed to eliminate post-PCR
      processing, enhance specificity, and provide quantitative data on starting
      template concentration. Each fluorogenic PCR assay detected a minimum of 10
      copies of target template, had comparable or greater sensitivity when compared
      directly with corollary gel detection PCR assays, and detected only targeted
      species when numerous Helicobacter spp. and other enteric bacteria were analyzed.
      Fluorogenic nuclease PCR analysis of fecal DNA samples obtained from numerous
      laboratory mice sources detected all samples with positive results by use of
      Helicobacter spp., H. hepaticus, H. bilis, and/or H. typhlonius gel detection PCR
      analysis, except for one sample that had positive results by H. typhlonius gel
      detection PCR but negative results by H. typhlonius fluorogenic nuclease PCR
      analysis. Among fecal DNA samples that were Helicobacter spp. negative by use of
      all gel detection PCR assays, the fluorogenic nuclease PCR assays detected target
      template in only one sample that was positive by use of the Helicobacter spp. and
      the H. bilis fluorogenic nuclease PCR assays. In conclusion, fluorogenic nuclease
      PCR assays provide sensitive, specific, and high-throughput diagnostic assays for
      detection of Helicobacter spp., H. hepaticus, H. bilis, and H. typhlonius in
      laboratory rodents, and the quantitative data generated by these assays make them
      potentially useful for bacterial load determination.

PMID- 12211280
TI  - Pseudocapillaria tomentosa, a nematode pathogen, and associated neoplasms of
      zebrafish (Danio rerio) kept in research colonies.
AB  - Infections with capillarid nematodes were observed in zebrafish (Danio rerio)
      kept at several research facilities and in a large carcinogen exposure study
      previously conducted at Oregon State University. We report a morphologic
      description that identifies the worm as Pseudocapillaria tomentosa, a common
      nematode of cyprinid and other fishes. Pathologic lesions associated with the
      infection ranged from inflammatory changes to aggressive neoplasms of the
      intestine (i.e., intestinal carcinomas and mixed malignant neoplasms). Capillarid
      nematodes may have intermediate or paratenic hosts. Using a laboratory
      transmission study, we confirmed that the parasite has a direct life cycle.

PMID- 12211281
TI  - Nucleic acid deletions and copy number in rats.
AB  - Rats fed either a cereal-based or purified diet of variable folate content
      (deficient, replete, or supplemented) inadvertently were infected with
      sialodacryoadenitis virus, which resulted in an increased frequency of hepatic
      mitochondrial DNA (mtDNA) deletions that persisted for three weeks after the
      period of acute signs of disease. The amount of the "common deletion" (4.8 kb,
      bases 8103-12937) in liver was measured by quantitative co-amplification of the
      mitochondrial D-loop and the mitochondrial deletion, using a real-time
      quantitative polymerase chain reaction assay. The relative abundance of mtDNA was
      determined by co-amplifying mitochondrial D-loop versus the rat beta-actin gene.
      Virus-infected rats had more mtDNA deletions (P < 0.0001) and higher copy number
      (P < 0.0001) than did uninfected animals. There was no effect of diet on
      frequency of deletions. Diet affected mtDNA relative abundance in the infected,
      but not the uninfected rats. Relative abundance was higher (P = 0.004) in rats of
      the high folate group than in rats of the low-folate or folate-replete groups,
      and was significantly higher in rats of the cereal diet group than that in those
      of the purified diet group. In conclusion, sialodacryoadenitis virus infection in
      rats was associated with increased frequency of hepatic mtDNA deletions. Thus,
      sialodacryoadenitis virus infection mitigated biological processes in the liver
      of rats, and mtDNA damage was modulated by diet.

PMID- 12211282
TI  - High mortality due to Tetrahymena sp. infection in laboratory-maintained
      zebrafish (Brachydanio rerio).
AB  - A large colony of laboratory zebrafish (Brachydanio rerio) used in the study of
      early vertebrate embryogenesis began experiencing acute, unexplained mortality
      that approached 100% among approximately 30-day-old resident fry. The initial
      differential diagnosis included ammonia, nitrite, or chlorine toxicosis, as well
      as iatrogenically induced toxicosis associated with improper sanitation
      procedures of laboratory equipment. Necropsy of dead and moribund fry prior to
      fixation revealed swarms of ovoid-shaped, motile, ciliated protozoa with a
      "spiraling football" motion. Wet mount preparations of various water samples also
      contained high numbers of similar protozoa. Histologic examination of affected
      fry revealed numerous, periodic acid-Schiff-positive forms within the body
      coelom, and epithelial and muscle tissues. The protozoa were consistent
      morphologically with members of the genus Tetrahymena, which is usually a free
      living, nonpathogenic ciliated protozoa in fresh and saltwater environments.
      Relevant disease associated with Tetrahymena spp. in viviparous fish has been
      reported as a result of concurrent disease, immunosuppression, or poor water
      quality conditions. To the authors' knowledge, this is the first report of an
      epizootic involving laboratory maintained zebrafish, and the diagnostic course
      and therapeutic interventions undertaken to alleviate Tetrahymena species
      associated clinical disease.

PMID- 12211283
TI  - Type-3 von willebrand's disease in a rhesus monkey (Macaca mulatta).
AB  - Severe type-3 von Willebrand's disease (vWD) was diagnosed in a young male rhesus
      monkey that had excessive bleeding from minor wounds. Plasma samples from the
      monkey had no detectable quantitative or functional von Willebrand factor (vWF),
      low Factor-VIII coagulant activity, and moderate prolongation of activated
      partial thromboplastin time. Testing of the affected monkey's extended family
      revealed a likely hereditary basis for the vWD, in that the sire and a paternal
      half-sister had markedly reduced plasma vWF concentration. Fresh whole blood was
      transfused to control frequent bleeding episodes throughout the monkey's life.
      Although vWD is the most common inherited bleeding disorder in humans and dogs,
      this is the first report of vWD in a nonhuman primate.

PMID- 12211284
TI  - Prevention of perinatal group B streptococcal disease. Revised guidelines from
      CDC.
AB  - Group B streptococcus (GBS) remains a leading cause of serious neonatal infection
      despite great progress in perinatal GBS disease prevention in the 1990s. In 1996,
      CDC, in collaboration with other agencies, published guidelines for the
      prevention of perinatal group B streptococcal disease (CDC. Prevention of
      perinatal group B streptococcal disease: a public health perspective. MMWR
      1996;45[RR-7]:1-24). Data collected after the issuance of the 1996 guidelines
      prompted reevaluation of prevention strategies at a meeting of clinical and
      public health representatives in November 2001. This report replaces CDC's 1996
      guidelines. The recommendations are based on available evidence and expert
      opinion where sufficient evidence was lacking. Although many of the
      recommendations in the 2002 guidelines are the same as those in 1996, they
      include some key changes: * Recommendation of universal prenatal screening for
      vaginal and rectal GBS colonization of all pregnant women at 35-37 weeks'
      gestation, based on recent documentation in a large retrospective cohort study of
      a strong protective effect of this culture-based screening strategy relative to
      the risk-based strategy * Updated prophylaxis regimens for women with penicillin
      allergy * Detailed instruction on prenatal specimen collection and expanded
      methods of GBS culture processing, including instructions on antimicrobial
      susceptibility testing * Recommendation against routine intrapartum antibiotic
      prophylaxis for GBS-colonized women undergoing planned cesarean deliveries who
      have not begun labor or had rupture of membranes * A suggested algorithm for
      management of patients with threatened preterm delivery * An updated algorithm
      for management of newborns exposed to intrapartum antibiotic prophylaxis Although
      universal screening for GBS colonization is anticipated to result in further
      reductions in the burden of GBS disease, the need to monitor for potential
      adverse consequences of intrapartum antibiotic use, such as emergence of
      bacterial antimicrobial resistance or increased incidence or severity of non-GBS
      neonatal pathogens, continues, and intrapartum antibiotics are still viewed as an
      interim strategy until GBS vaccines achieve licensure.

PMID- 12211285
TI  - A critique of social capital.
AB  - This article critiques the concepts of communitarianism and social capital as
      used in the United States and in Europe. For the United States, the author
      focuses on Robert Putnam's understanding of both concepts, showing that the
      apolitical analysis of the Progressive Era, of the progressive developments in
      Northern Italy, and of the situation of labor unions in the United States is not
      only insufficient but wrong. The critique also includes the difference between
      U.S. communitarianism and its European versions, Christian democracy and New
      Labour, and the limitations of both approaches. The uses and misuses of these
      concepts in the political debate are discussed.

PMID- 12211286
TI  - How International Monetary Fund and World Bank policies undermine labor power and
      rights.
AB  - Based on reviews of hundreds of loan and project documents from the International
      Monetary Fund (IMF) and World Bank, this article provides detailed evidentiary
      support for critics who have long claimed that the international financial
      institutions require Third World countries to adopt policies that harm the
      interests of working people. After reviewing loan documents between the IMF and
      World Bank and 26 countries, the authors show that the institutions' loan
      conditionalities include a variety of provisions that undermine labor rights,
      labor power, and tens of millions of workers' standard of living. These include
      downsizing of the civil service and privatization of government-owned
      enterprises; promotion of labor flexibility: the notion that firms should be able
      to hire and fire workers, or change terms and conditions of work, with minimal
      regulatory restrictions; mandated wage rate reductions, minimum-wage reductions
      or containment, and spreading the wage gap between government employees and
      managers; and pension reforms, including privatization, that cut social security
      benefits. These labor-related policies take place in the context of broader IMF
      and World Bank structural adjustment packages that emphasize trade
      liberalization, with macroeconomic policies that further advance corporate
      interests at the expense of labor.

PMID- 12211287
TI  - Case studies of violations of workers' freedom of association: migrant
      agricultural workers.
AB  - As part of its report "Unfair Advantage: Workers' Freedom of Association in the
      United States under International Human Rights Standards," Human Rights Watch
      conducted a series of case studies in a dozen states, covering a variety of
      industries and employment sectors, analyzing the U.S. experience in the light of
      both national law and international human rights and labor rights norms.
      Presented here are the case studies of migrant agricultural workers.

PMID- 12211288
TI  - Reintegration: public or private responsibility? Consequences of Dutch and Danish
      policies toward work-disabled persons.
AB  - The Scandinavian welfare states are known for their universal social security
      coverage and high labor-market participation rates for all groups in society. The
      institutional setup in continental European welfare states, on the other hand, is
      said to foster a divide between employed persons and persons outside the labor
      market. In the area of disability policies, The Netherlands and Denmark
      illustrate this distinction. In The Netherlands, strong ties exist between the
      employer and the sick-listed worker, both because of solid job-protection
      legislation and because the financing of sickness and disability benefits is
      closely linked to the individual employer. In contrast, employer responsibility
      is limited in Denmark, where an extensive responsibility rests with public
      authorities. The author investigates the consequences of these differences using
      panel data on Dutch and Danish long-term sick-listed workers. The findings show
      that the strong ties in The Netherlands between employers and sick-listed workers
      enhance labor-market reintegration of long-term sick-listed workers. A
      significant drawback of the Dutch policy, however, is that employers refrain from
      employing persons with a high risk of falling ill. As a result, Dutch disability
      policy leads to a bigger insider-outsider divide than Danish policy.

PMID- 12211289
TI  - WTO confidential: the case of asbestos. World Trade Organization.
AB  - The World Trade Organization (WTO), created in 1995, adjudicates "trade disputes"
      between member nations in cases with great human rights, cultural, environmental,
      and public health significance. Throughout the process of dispute resolution and
      even after a case is concluded, very little of what happens is made accessible to
      the public. However, it is one thing to criticize the WTO for its lack of
      transparency from outside the process, and another to critically examine what was
      withheld from disclosure and what dangers that presents. This is the inside story
      from a scientific adviser to one of the parties in a WTO case, analyzing what
      happened from a public health point of view. This analysis concludes that the
      public health justification of banning asbestos was accepted in the end by the
      economists at the WTO, despite the WTO's bias in favoring the party (Canada)
      making the free trade challenge (to public health legislation, in this case) in
      numerous stages of the process, despite the WTO's utter lack of expertise in
      science, medicine, engineering, and public health, and despite important
      erroneous statements made to the WTO under the cover of confidentiality. Despite
      its result, this case illustrates that the WTO's threat to national sovereignty
      could never withstand the light of day, that the people of the world would reject
      this dangerous free trade fundamentalism if the limitations and dangers of the
      process were open for all to see.

PMID- 12211290
TI  - The World Health Report 2000: World Health Organization health policy steering
      off course-changed values, poor evidence, and lack of accountability.
AB  - The World Health Report 2000 on health systems has raised concerns about its
      political biases, its methods and indicators, and its lack of reliable data.
      Tracing the origins of the Report, this article argues that it counteracts many
      of the concerns that gave rise to preparation of the Report in the first place.
      The mutually agreed-upon value-base, expressed in the Health for All strategy,
      has been largely abandoned. The Report includes contradictory messages, and many
      of its recommendations are not evidence-based. Furthermore, the ranking of
      countries according to their health systems' performance is not useful for health
      policy-making, even if the methods and data could be improved. Because the member
      states and governing bodies of the WHO were not consulted during the production
      of the Report, the WHO secretariat has not received a mandate to change the value
      base of the WHO's health policy or the aims of the Report. The WHO should return
      to its mandate as a normative intergovernmental U.N. agency on health.

PMID- 12211291
TI  - Occupational medicine: toward a worker/patient empowerment approach to
      occupational illness.
AB  - Clinicians practicing occupational medicine are increasingly confronted with
      patients who have complex illnesses with chronic nonspecific symptoms. Most
      clinicians use the traditional tools of biomedicine to diagnose and treat the
      illness, determine etiology, and assess disability. This article argues that the
      biomedical approach is inadequate to effectively evaluate and treat occupational
      illness. After reviewing several critiques of biomedicine, including
      biopsychosocial, feminist, class, and critical theory/postmodern perspectives,
      the author offers an alternative approach that builds on aspects of these
      perspectives as well as the "popular education" work of Paulo Freire. Constraints
      on, and possibilities for, the development of an alternative approach that
      attempts to build patients' capacities for transformative action are explored.

PMID- 12211292
TI  - Breaking the wall of silence: AIDS policy and politics in Nigeria.
AB  - AIDS was first diagnosed in Nigeria in 1986. By that time, the government had
      enough information from experiences in other African countries to goad it into
      quickly establishing a control program. Nigeria's National AIDS Control program,
      however, fell victim to years of military arbitrariness and uncertainty. It was
      underfunded and had three directors in as many years. This arbitrariness and
      general lukewarm response from government occurred despite rapid increases in
      seroprevalence rates. Available data indicate a national prevalence of 5.4
      percent and rates as high as 30 percent among some "high-risk" groups; as many as
      10 to 15 persons with full-blown AIDS are admitted weekly in some tertiary
      facilities. Experiences in communities show an already heavy and growing burden.
      The nonchalance of past military regimes is gradually being reversed with
      Nigeria's return to civil rule in May 1999. Perhaps because of the fragmented
      statistics and the government's seeming conspiracy of silence, Nigeria is not
      included in the count of African countries with high HIV/AIDS prevalence. The
      author suggests that the new democratic government needs to go beyond professed
      commitment to demonstrable action to halt the spread and address social and other
      impacts of the epidemic.

PMID- 12211293
TI  - Do minorities in the United States receive fewer mental health services than
      whites?
AB  - Older studies have found that minorities in the United States receive fewer
      mental health services than whites. This analysis compares rates of outpatient
      mental health treatment according to race and ethnicity using more recent,
      population-based data, from the 1997 National Ambulatory Medical Care Survey and
      National Hospital Ambulatory Medical Care Survey. The authors calculated visit
      rates per 1,000 population to either primary care or psychiatric providers for
      mental health counseling, psychotherapy, and psychiatric drug therapy. In the
      primary care setting, Hispanics and blacks had lower visit rates (per 1,000
      population) for drug therapy than whites (48.3 and 73.7 vs. 109.0; P <.0001 and P
      < .01, respectively). Blacks also had a lower visit rate for talk therapy (mental
      health counseling or psychotherapy) than whites (23.6 vs. 42.5; P < .01). In the
      psychiatric setting, Hispanics and blacks had lower visit rates than whites for
      talk therapy (38.4 and 33.6 vs. 85.1; P < .0001 for both comparisons) and drug
      therapy (38.3 and 29.1 vs. 71.8; P < .0001 for both comparisons). These results
      indicate that minorities receive about half as much outpatient mental health care
      as whites.

PMID- 12211295
TI  - Health as an essential human need, a right of citizenship, and a public good:
      health for all is possible and necessary.
AB  - This statement to the second World Social Forum, presented in Porto Alegre on
      January 30, 2002, summarizes the conclusions of the first International Forum for
      the Defense of the Health of People. The statement denounces macroeconomic
      adjustment policies and the militarization of international relationships for
      their devastating effects on people's health and quality of life, and proposes a
      wide public debate and action on a development model that moves toward equity and
      promotes health and well-being as a human right and a public good.

PMID- 12211294
TI  - A review of data on the health sector of the United States January 2002.
AB  - This report presents data on the state of U.S. health care at the end of 2001. It
      provides information on access to health care, inequalities in incomes and
      medical care, the increasing costs of health care and health insurance, and the
      role of corporate money in the provision of health care and the development,
      marketing, and patenting of pharmaceuticals. The author also looks at the state
      of health maintenance organizations, the results of some recent surveys on
      physicians' and public opinion on managed care, and news about the nursing
      professions. Also provided is an update on Congressional activity on health care
      legislation, the role of health care industry money in politics, and some
      developments in health care systems elsewhere in the world.

PMID- 12211296
TI  - East Timor in transition: health and health care.
AB  - East Timor was liberated from 400 years of conquest and exploitation in an armed
      struggle that ended, in September 1999, in a conflagration that destroyed its
      social and physical infrastructures. For two years the territory has been under
      United Nations administration. Political conditions remain unstable as the result
      of many intrinsic and external factors. Its economy continues to depend upon
      infusions of funds from multilateral, bilateral, and private sources. Efforts by
      expatriates to introduce Euro-American cultural and technical models have been
      applied to the factors that determine health, with modest results. East Timor
      expects to be totally independent of foreign control early in 2002. Its future
      health will depend upon continuing collaboration between international and local
      leadership in evolving effective government, economy, and health services
      designed, managed, and executed by Timorese.

PMID- 12211297
TI  - Comparative analysis of allozyme, random amplified polymorphic DNA, and
      microsatellite polymorphism on Chinese native chickens.
AB  - Allozyme, random amplified polymorphic DNA (RAPD), and microsatellite
      polymorphisms were examined and compared among five native populations of Chinese
      chickens, two fast-growing broiler lines, and one layer line. Three assay systems
      resulted in a different average heterozygosity or gene diversity in each of the
      eight populations. The lowest average heterozygosity was obtained with allozyme
      analysis (0.2209), intermediate heterozygosity was obtained with RAPD (0.2632),
      and the highest heterozygosity was observed with microsatellite analysis
      (0.7591). The genetic distances among all populations measured by three methods
      were also different. Allozyme data showed close relationships between Chinese
      native chickens and the two broiler lines, but they were both remotely related to
      the layer line. Microsatellite polymorphism analysis was similar to the allozyme
      analysis but genetic distances from RAPD showed a close relationship between
      Chinese native chickens and broiler and layer chickens.

PMID- 12211298
TI  - Influence of mating ratio and group size on indicators of fearfulness and stress
      of hens and cocks.
AB  - The effects of the male to female mating ratio on the heterophil to lymphocyte
      ratio and duration of tonic immobility (indicators of stress and fearfulness,
      respectively) were analyzed in two different experiments with different group
      sizes. In Experiment 1, four different mating ratios (1:11, 1:5, 1:3, and 1:1)
      and 10 different Spanish breeds of chickens were used; each breeding pen had 12
      birds. In Experiment 2, two different mating ratios (1:11 and 1:1) and four
      breeds were analyzed; 60 birds were used. There were significant differences
      among mating ratios (P < 0.001) for the heterophil to lymphocyte ratio in females
      of both group sizes. Hens housed with a mating ratio of 1:1 had higher heterophil
      to lymphocyte ratios than did hens housed with a 1:11 mating ratio in the group
      with 12 birds (0.53 vs. 0.35) or that with 60 birds (0.76 vs. 0.37). Hens in a
      mating ratio of 1:1 had significant heterophilia and lymphopenia (P < 0.001). The
      1:5 and 1:3 male to female mating ratios did not differ significantly from the
      1:11 mating ratio. The effect of the group size was significant when the mating
      ratio was 1:1 but not when it was 1:11. There was no significant difference among
      mating ratios in terms of tonic immobility for hens. Cocks housed with a mating
      ratio of 1:1 and a group size of 60 birds showed shorter duration of tonic
      immobility (P < 0.05) than did cocks housed with a 1:11 mating ratio (203 vs. 296
      s). The results suggest that very high mating ratios should not be used in
      conservation populations because it increases physiological and psychological
      stress responses.

PMID- 12211299
TI  - Concentration of immnoglobulin G in plasma varies among 6C.7 recombinant congenic
      strains of chickens.
AB  - Chicken Lines 63 and 72 were inbred during selection for resistance or
      susceptibility to viral-induced tumors. A sandwich ELISA assay was adapted to
      define the milligrams per milliliter of Ig-gamma (IgG) in plasma from chickens of
      Lines 63 and 72, as well as 19 recombinant congenic strains (RCS). Each RCS
      resulted from a 7(2) x 6(3) F(1) and two backcross matings using 63 as the
      recurrent female line. The IgG levels in the RCS were evaluated after four to
      seven generations of sib-matings, when each RCS was becoming inbred and fixed for
      a different 12.5% of the 72 genome. In three generations approximately 24-wk-old
      chickens of Line 72 had higher levels of plasma IgG than chickens of Line 63 (P <
      0.05). None of the RCS had repeatable IgG levels comparable to Line 7(2).
      However, in the last two generations, two of the 18 RCS had higher IgG levels
      than nine with low IgG levels (P < 0.05). There was no correlation between an IgG
      level of a RCS and resistance to Marek's disease. It was concluded that selected
      RCS may be useful for identifying genes that determine differences in IgG levels,
      as well as for understanding the relationship between genes, IgG levels, and
      other traits that differ between Lines 63 and 72.

PMID- 12211300
TI  - Heterosis of growth and reproductive traits in fowl.
AB  - Long-term divergent selection for high (HH) and low (LL) BW at 56 d of age in
      White Plymouth Rock chickens resulted in deviations from a typical chronological
      timeline for reproductive development. Line HH chickens of the 42nd generation of
      selection (S(42)) were heavier at 28, 56, 168, and 266 d of age, as well as at
      sexual maturity than those from line LL of the same generation, and commenced egg
      production at a younger age (188 d vs. 217 d). Once the LL chickens reached
      sexual maturity, 99.5% of their ovulations resulted in normal oviposits, in
      contrast to 94.6% for HH females. Heterosis, as measured by differences of F(1)
      progeny from the parental lines, can have a positive or negative sign. Although
      negative heterosis does not imply inferiority, results may be confusing because,
      depending on the trait, positive or negative can biologically be the phenotype
      that is preferred. Heterosis was calculated using coefficients of variation and
      means for reciprocal crosses from S(41) parents of the selected lines. Growth and
      reproductive traits were measured in this experiment. In almost all cases,
      heterosis calculated using coefficients of variation had a narrower range of
      magnitudes.

PMID- 12211301
TI  - Effect of selection for growth rate on embryonic breast muscle development in
      turkeys.
AB  - Muscle development at 20 and 25 d of incubation was studied in a randombred
      control line (RBC2), a subline (F) of RBC2 selected only for increased 16-wk BW,
      a commercial sire line (B), and reciprocal crosses of the F and B lines. Muscle
      samples from three males and three females of each genetic group were collected
      in such a manner to avoid contraction. After fixing, the muscles were stained
      with hematoxylin and eosin, measurements of muscle fiber width, muscle fiber
      bundle length and width, number of fibers within a 15.6 microm2 area, and
      extracellular matrix perimysial (PW) and endomysial (EW) width were taken with an
      Olympus XI 70 microscope equipped with an Olympus Magna Fire digital camera
      linked to Image Pro software. From each slide, 20 measurements were taken for
      each characteristic analyzed. In most of the muscle traits measured, additive
      genetic variation, as indicated by line differences, occurred when the RBC2 line
      was included in the comparison of pure lines. However, when only the B and F
      lines were compared, line differences were less frequent. In comparisons of the B
      and F lines and their reciprocal crosses, heterosis, as measured by contrasts of
      the average of the pure lines and the average of the reciprocal crosses, was an
      important source of variation for individual fiber measurements (negative) and
      extracellular space (positive) at 20 d of incubation but was less important at 25
      d of incubation. No significant interactions between genetic group and sex were
      noted at 20 d of incubation, but such interactions were frequent at 25 d of
      incubation. These results suggest that muscle organizational differences between
      the two sexes begin to occur between these two ages and are not the same for
      different genetic groups.

PMID- 12211302
TI  - In vitro activity of therapeutic drugs against Histomonas meleagridis (Smith,
      1895).
AB  - Histomoniasis or blackhead is a life-threatening disease of turkeys that is
      caused by a flagellated protozoan, Histomonas meleagridis. The development of an
      assay to measure the sensitivity of drugs traditionally used against this
      parasite, as reputed to be effective against other protozoan parasites, is
      described. The in vitro minimum lethal concentrations (MLC), time for drug
      efficacy, and parasite viability after removal of residual drugs were determined.
      Three of the 10 tested drugs, fenbendazole, albendazole, and sulfadiazine, were
      found to be ineffective against H. meleagridis. Nifursol, the only compound still
      authorized as a feed additive in Europe, is an inhibiting agent but is not lethal
      in vitro. Roxarsone, an arsenical derivate similar to nitarsone (the only
      authorized drug in United States), is effective at high concentration (200
      microg/mL) after a long exposure (48 h). The lethal activity of dimetridazole,
      metronidazole, ronidazole, tinidazole, and furazolidone in vitro was
      demonstrated. Dimetridazole (MLC = 25 microg/mL after 6 h of exposure),
      metronidazole (MLC = 50 microg/mL after 24 h), and furazolidone (MLC = 50
      microg/mL after 24 h) are rapidly effective at low concentrations. These results
      confirm the effectiveness of dimetridazole, a drug that has been used in the
      treatment and prevention of blackhead. In May 2002 this compound was removed as
      feed additive in Europe.

PMID- 12211303
TI  - Detection of experimental Salmonella enteritidis and S. typhimurium infections in
      laying hens by fluorescence polarization assay for egg yolk antibodies.
AB  - Identifying infected laying flocks is a critical component in efforts to prevent
      eggborne transmission of Salmonella enteritidis to humans. In the present study,
      egg yolk samples from experimentally infected chickens were tested for specific
      antibodies with a very rapid fluorescence polarization assay using tracers
      prepared from the O-polysaccharides of S. enteritidis and S. typhimurium and a
      conventional ELISA using an S. enteritidis flagellin antigen. In two trials,
      groups of specific-pathogen-free laying hens were infected orally with 106 or
      10(8) cfu of S. enteritidis (phage type 13a) or with 10(8) cfu of S. typhimurium.
      Eggs were collected during five weekly postinoculation intervals. Both
      fluorescence polarization and ELISA detected the majority of hens infected with
      S. enteritidis at either dose level, although they also frequently cross-reacted
      with samples from hens infected with S. typhimurium. Fluorescence polarization
      with an S. typhimurium tracer was likewise able to consistently detect S.
      typhimurium infection but also tended to cross-react with samples from hens
      infected with S. enteritidis. Fluorescence polarization appears to offer a simple
      and rapid alternative to conventional serological methodology, although concerns
      about specificity may limit the usefulness of antibody testing data.

PMID- 12211304
TI  - Reduction of eggshell aerobic plate counts by ultraviolet irradiation.
AB  - The effects of 254 nm ultraviolet light (UV) radiation on aerobic plate count
      (APC) of egg shells were investigated. In the first experiment, eggs were exposed
      to UV treatment (7.35 mW/cm2) for 0, 15, 30, and 60 s. Three eggs from each
      treatment were aseptically collected and placed into sterile plastic bags
      containing 50 mL of sterile phosphate-buffered solution. Serial dilutions of the
      phosphate-buffered solution were plated on aerobic plate count agar and incubated
      at 37 C for 48 h. Exposure of eggshells to 30 and 60 s UV significantly reduced
      aerobic plate counts compared to untreated eggs. Exposure to 60 s of UV resulted
      in a 2 to 3 log10 cfu/egg APC reduction and reduced counts below detectable
      levels. In the second experiment, UV lights were placed in a chamber equipped
      with a commercial-style egg conveyor. A UV treatment of 7.5 mW/cm2 and time
      intervals of 0, 12, 36, and 48 s were used. Three eggs were placed consecutively
      on the conveyor and passed through the chamber. The center egg was selected for
      APC evaluation. Sample size, dilution, plating, and incubation procedures were
      used as described for the first experiment. A significant 1 to 2 log10 reduction
      in colony-forming units per egg between the eggs treated 48 s to the untreated
      eggs was detected. The results of these studies show that UV light treatment at
      high intensities and low time intervals has the potential to reduce aerobic plate
      counts of eggshells.

PMID- 12211305
TI  - In situ detection and quantification of bursa of fabricius cellular proliferation
      or apoptosis in normal or steroid-treated neonatal chicks.
AB  - Apoptosis, or programmed cell death, is believed to be the mechanism for
      depletion of lymphocytes recognizing self-antigens following clonal expansion in
      the bursa of Fabricius. Although bursal apoptosis has previously been shown to
      increase following in vivo exposure to glucocorticoids, the microanatomical site
      of induced or normal apoptosis has not been unequivocally established. Presently,
      we adapted the existing terminal deoxynucleotidal transferase-mediated dUTP nick
      end labeling (TUNEL) assay for use with neonatal bursae. Similar to previous
      reports, TUNEL revealed that normal apoptosis is preferentially, but not
      exclusively, ongoing in bursal follicular cortical cells. Administration of a
      single dose of a synthetic glucocorticoid (dexamethasone) or androgen (19
      nortestosterone) did not significantly (P < 0.05) alter follicular lymphocyte
      numbers or apoptosis per unit of area at the time points evaluated post
      administration (6 or 24 h). However, administration of 19-Nortestosterone
      increased the interfollicular epithelial thickness, a change usually associated
      with edema, within 6 h following treatment. Additionally, administration of the
      androgen 19-nortestosterone significantly decreased the number of proliferating
      cells as detected using mouse anti-proliferating cell nuclear antigen (PCNA) as a
      primary immunohistochemical antibody. In normal (control) bursal sections,
      occasional follicles consisting of predominantly apoptotic cells were observed
      (0.26% of follicles). Such follicles were consistently one-tenth the area of
      normal follicles. This incidental finding may suggest occasional occurrence of a
      common signal for deletion, such as a common integral or clonal mistake, viral
      infection, or an aberrant paracrine signal.

PMID- 12211306
TI  - The influence of labile dietary methyl donors on the arginine requirement of
      young broiler chicks.
AB  - Two experiments were conducted with Ross x Ross boiler chicks in battery brooders
      from 1 to 14 d of age to determine the influence of dietary methyl donors on the
      Arg requirement of young broiler chicks. Experiment 1 had a 6 x 2 factorial
      design, with six levels of Arg supplementation (0, 0.1, 0.2, 0.3, 0.4, and 0.5%)
      and two levels of DL-Met supplementation (0 and 0.2% of the diet). The design of
      Experiment 2 was identical to Experiment 1, except that a second source of labile
      methyl groups was added, 0.2% betaine (6 x 3 factorial arrangement). Both
      experiments had four replicate pens of 10 chicks each per treatment. The basal
      diet was based on corn (34.52%), whey (26.96%), corn gluten meal (16.53%),
      soybean meal (11.74%), and poultry fat (23% CP and 3.20 kcal/g of ME). At 14 d,
      three chicks per replicate were randomly killed, and breast muscle was collected
      and pooled for creatine analysis. The broken-line linear model was used to
      estimate the Arg requirements of the chicks. There were no differences in Arg
      requirements due to methyl source so the data were pooled. In Experiment 1, the
      Arg requirements were 1.17 +/- 0.04% for gain, 1.23 +/- 0.03% for feed conversion
      ratio (FCR), and 1.18 +/- 0.03% for muscle creatine, when the diet contained 0.45
      or 0.65% Met. In Experiment 2, the Arg requirements were 1.20 +/- 0.05% for gain,
      1.23 +/- 0.03% for FCR, and 1.26 +/- 0.02% for muscle creatine. There was no
      apparent difference in the Arg requirement of young broilers due to methyl donor
      supplementation.

PMID- 12211307
TI  - An investigation of calcium citrate-malate as a calcium source for young broiler
      chicks.
AB  - Two experiments were conducted to compare a sample of calcium citrate-malate (CC
      M) with a sample of commercial-grade limestone in starting broiler chick diets.
      In the first experiment, with 0.7 or 0.9% calcium from limestone or CC-M, no
      differences in bone development (dry fat-free tibia, tibia weight, tibia ash, or
      tibia calcium) were observed due to calcium source. However, chicks fed the diets
      based on CC-M had better 0- to 18-d body weight gains and feed conversion ratios
      than those fed limestone. In the second experiment with 0.50, 0.55, 0.60, 0.65,
      or 0.70% calcium from limestone or CC-M, chicks again had better body weight
      gains when fed CC-M compared to those fed limestone. Chicks fed diets based on CC
      M and NaP2PO4 had very similar bone development and tibial dyschondroplasia
      pathology to those fed limestone and Na2H2PO4. However, a control group of chicks
      fed 0.70% calcium from limestone and dicalcium phosphate did not grow as well as
      the others and had lower weights of tibia and tibial bone ash, calcium, and
      phosphorus compared to the others. It is concluded that CC-M is a good calcium
      source, comparable in bioavailability to limestone. Although CC-M may improve
      broiler growth, its action is not through increased bioavailability of calcium.

PMID- 12211308
TI  - Effect of low-protein diets on growth performance and body composition of broiler
      chicks.
AB  - Three experiments were conducted to investigate effects of dietary manipulations
      to improve growth performance and whole-body composition of broiler chicks fed
      low-protein diets supplemented with crystalline amino acids. In all experiments,
      male chicks (1 d old) were fed a common corn-soybean meal diet (23% CP) for 7 d
      and subsequently allotted to treatment diets in a completely randomized design
      (10 chicks per floor pen, six replications). Chicks had free access to the
      isoenergetic diets (3,200 kcal MEn/kg) for 2 wk, after which chicks were weighed
      and then fasted for 24 h, and the whole-body DM, N, and ether extract contents of
      two chicks per pen (and six baseline chicks) were determined. In Experiment 1,
      Gln or Asn replaced 1% triammonium citrate in the low-protein diet (19% CP). In
      Experiments 2 and 3, dietary concentrations of crystalline essential and
      nonessential amino acids, respectively, were increased incrementally in the low
      protein diets (19 to 20% CP). In all experiments, chicks fed low-protein diets
      grew slower, used feed less efficiently, and retained less N and more ether
      extract than chicks fed the control diets (P < or = 0.05), despite additions of
      crystalline Gln or Asn and despite increased dietary concentrations of
      crystalline essential and nonessential amino acids. Chicks fed low-protein diets
      excreted less N (P < 0.001) than did chicks fed the high-protein diets, and N
      excretion increased linearly (P < 0.001) with N intake. In summary, low-protein
      diets failed to support equal growth performance to that of high-protein control
      diets.

PMID- 12211309
TI  - Prediction of whole-body composition from the whole-body dry matter percentage of
      three-week-old broiler chicks.
AB  - Whole carcasses of 3-wk-old broiler chicks from four independent experiments were
      analyzed for percentage of whole-body DM, ether extract, and CP. The percentage
      of whole-body ash was calculated by the difference among DM, ether extract, and
      CP. A linear relationship between percentage whole-body DM and percentage whole
      body ether extract (P < 0.001; r2 = 0.798) was found, but no relationships were
      detected between percentage whole-body DM and percentage whole-body CP (P = 0.29;
      r2 = 0.010). The percentage of whole-body ash was moderately correlated with the
      percentage of whole-body DM (P = 0.04; r2 = 0.036). In conclusion, the percentage
      of whole-body ether extract of 3-wk-old broiler chicks can be predicted from the
      percentage of whole-body DM by using the prediction equation Y = 0.961x - 17.855.
      Neither the percentages of whole-body CP nor ash could be accurately predicted
      from the wholebody DM percentage.

PMID- 12211310
TI  - Effects of microbial phytase supplementation on mineral utilization and serum
      enzyme activities in broiler chicks fed different levels of phosphorus.
AB  - An experiment was conducted to study the effect of microbial phytase (Natuphos
      500) supplementation in chicks (0 to 6 wk of age) fed different levels of
      nonphytate phosphorus (nPP) on performance, mineral retention, bone and plasma
      minerals and serum enzyme activities. Data were analyzed as a 2 x 2 factorial
      arrangement with two levels of nPP for age periods of 1-d-old to 3 wk (0.35 and
      0.22%) and 3 to 6 wk (0.27 and 0.14%) and two levels of phytase (0 and 500 U/kg)
      in each period. A positive control, adequate in nPP and Ca without phytase, was
      used. The low-nPP diets caused a negative effect on the performance (P < 0.05)
      compared to the normalnPP diet. Phytase had a favorable effect on weight gain at
      3 wk (P < 0.004) and 6 wk (P < 0.0475) of age and on feed consumption only at 3
      wk (P < 0.0106). Feed efficiency was not affected at any stage by addition of
      phytase. Performances of chicks fed with 0.35 and 0.27% nPP and phytase were
      comparable to those obtained with the normal-nPP diets. Decreasing nPP content in
      the diet increased (P < 0.0001) P retention at 3 and 6 wk of age, increased Mg
      retention at 6 wk, and decreased (P < 0.0001) Ca and Zn retentions at 3 and 6 wk,
      respectively. Phytase supplementation increased (P < 0.0001) Ca, P, Mg, and Zn
      retention at 3 and 6 wk of age. Likewise, the decrease in nPP content in the diet
      caused a significant reduction of tibia ash (P < 0.0023) and Mg content (P <
      0.0001) in tibia ash and reduced liver (P < 0.0240), spleen (P < 0.0176), and
      tibia (P < 0.0001) weights. Similarly, Ca (P < 0.0369) and Zn (P < 0.0181)
      contents in tibia ash were increased in response to decreasing nPP levels in the
      diet. Phytase supplementation increased tibia weight (P < 0.0019), tibia ash (P <
      0.0021), and Mg (P < 0.0339) and Zn (P < 0.0353) concentrations and reduced (P <
      0.0161) the relative liver weight. By decreasing nPP levels in the diet, plasma
      Ca (P < 0.0001), Mg (P < 0.0001) and Zn (P < 0.0048) concentrations, and alkaline
      phosphatase (ALP) activity (P < 0.0299) increased, and plasma P content (P <
      0.0001), aspartate aminotransferase (AST) activity (P < 0.0001), and total
      protein (TP) content (P < 0.0050) were reduced. Phytase supplementation increased
      plasma P level (P < 0.0001) and serum AST activity (P < 0.0049), reduced plasma
      Ca (P < 0.0001) and Mg (P < 0.0050) contents, and reduced serum alanine
      aminotransferase (ALT) (P < 0.0048), ALP (P < 0.0001) and lactate dehydrogenase
      (LDH) (P < 0.0192) activities. Plasma Zn was not affected by phytase
      supplementation. These results demonstrated that microbial phytase
      supplementation to low-P diets improved performance; P, Ca, Mg, and Zn use; and
      tibia weight and relative liver weight in broiler chickens. Likewise, serum AST,
      ALT, ALP, and LDH activities, as well as TP concentration, were also affected by
      phytase supplementation.

PMID- 12211311
TI  - Microstructure and mineral content of femora in male turkeys with and without
      fractures.
AB  - Microscopic and radiographic observations, as well as ash, calcium, phosphorus,
      copper, manganese, and zinc concentrations, were evaluated from femora of 32- to
      35-wk-old male turkeys from two different farms (A and B). Turkeys from Farm A
      were divided into birds with femoral fracture (AF) and without femoral fracture
      (ANF). Turkeys from Farm B did not have femoral fractures (BNF). In the mid
      diaphyseal cortex of turkeys without femoral fractures, collagen fibers were
      evenly distributed parallel to the transverse plane of bone surface. In contrast,
      collagen fibers were disorganized and the cortex was osteoporotic in turkeys with
      femoral fractures. Each turkey with femoral fractures also had callus on the
      mediocaudal region of the femoral middiaphysis. The periosteal callus was
      interrupted at the insertion of the puboischiofemoralis muscle. Muscle attachment
      to the bone might have interfered with the formation of periosteal callus. The
      concentration of calcium was lower in the cortex of turkeys in group AF compared
      to turkeys in groups ANF and BNF. The focal nature of the callus, along with the
      low levels of calcium, is indicative of a local repair response with alteration
      in cortical structure and altered concentrations of minerals in the cortex. These
      changes in the bone and the routine handling of the birds might have predisposed
      the turkeys to complete fractures of the femur.

PMID- 12211312
TI  - The effect of hepatocyte growth factor on turkey satellite cell proliferation and
      differentiation.
AB  - The effect of hepatocyte growth factor (HGF) on turkey satellite cell
      proliferation and differentiation was examined in cell culture. Satellite cell
      clones were established from one muscle of an individual turkey. The results
      showed that HGF is a potent activator and mitogen of turkey satellite cells and
      embryonic myoblasts with maximal stimulation at 1 ng/mL. HGF is also an inhibitor
      of differentiation of turkey satellite cells. Heterogeneity in the responsiveness
      to HGF in the turkey satellite cell population was observed between clones
      selected for fast (Early) or slow (Late) rates of proliferation. However, two
      other Early clones exhibited responses similar to those of two other Late clones.
      When combined with insulin-like growth factor (IGF) and fibroblast growth factor
      (FGF), singularly or in combination, HGF did not exert any additive or
      synergistic effects on Early or Late clone proliferation. Whereas when combined
      with IGF, FGF, and platelet-derived growth factor (PDGF), HGF significantly
      stimulated proliferation of the Late clone but not the Early clone. Addition of
      anti-HGF antibody to culture media diminished proliferation and provided evidence
      of autocrine production of HGF by turkey satellite cell cultures. Heterogeneity
      also exists in the turkey satellite cell population with respect to autocrine
      production of HGF.

PMID- 12211313
TI  - Comparing growth and condition in post release juvenile common pheasants on
      different diets.
AB  - ABSTRACT We studied juvenile common pheasants Phasianus colchicus in 10 large
      open-topped release pens in woodlands on a shooting estate in southern England in
      1998. In six pens the pheasants were fed a pelleted high-protein feed from 6 to
      16 wk of age; in the four other pens they were fed the diet from 6 to 10 wk and
      then wheat grain only from 10 to 16 wk. Natural plant and animal food was also
      available to the birds in and around the release pens. When a sample of
      previously tagged, numbered, and weighed birds was caught from each pen and
      reweighed at 16 wk of age, we noted that birds from pens that remained on the
      high-protein feed had gained more weight than those from pens in which the diet
      was switched to grain only (P < 0.05). Of approximately 500 tagged birds
      collected during shooting days between 5 and 15 wk later, differences in body
      mass gain between groups were still significant (P < 0.05). A subsample, 50 males
      and 50 females aged 22 to 24 wk, of tagged birds that were shot were kept for
      postmortem examination. From this smaller sample, the differences in body mass
      were not significant (P > 0.05). Breast muscle mass and tarsal length did not
      differ between treatments. However cloacal fat was higher in the birds fed a high
      protein diet (P < 0.05), suggesting that the results relating to body mass were
      due to differences in fat accumulation. Most pheasants examined postmortem
      contained the gut nematode Heterakis gallinarum with an average burden of 118 +/-
      14 worms per bird. Although the abundance of these worms was not related to diet,
      it was negatively correlated with body mass, breast muscle mass, and cloacal fat
      (P < 0.05).

PMID- 12211314
TI  - Intravenous micro-particle injections and pulmonary hypertension in broiler
      chickens: acute post-injection mortality and ascites susceptibility.
AB  - Intravenously injected micro-particles become trapped within the pulmonary
      vasculature where they increase the resistance to blood flow and trigger
      pulmonary hypertension. We tested the hypothesis that i.v. micro-particle
      injections can be used to trigger acute (24 to 48 h) post-injection mortality in
      broilers having the most limited pulmonary vascular capacity, or ascites in
      broilers whose marginal cardiopulmonary capacity renders them susceptible to
      pulmonary hypertension syndrome (PHS). Progressive inflammation-associated
      responses were initiated within the lung parenchyma by 10 to 80 microm diameter
      dextran polymer (Sephadex) and 30 microm diameter cellulose micro-particles,
      leading to the scavenging of Sephadex micro-particles from the pulmonary
      vasculature by <5 d post-injection, whereas the cellulose micro-particles
      persisted for >7 d post-injection. The persistency and size of the cellulose
      apparently facilitated chronic occlusion of blood flow through precapillary
      arterioles, thereby triggering appreciable post-injection mortality and PHS at
      relatively low injection volumes (0.3 to 0.6 mL at 0.02 g/mL). In contrast, the
      small size of the polystyrene microspheres (15 microm), and the lack of
      persistency of the Sephadex micro-particles, apparently precluded the reliable
      occurrence of post-injection mortality or PHS until higher volumes (>0.8 mL at
      0.02 g/mL) were injected. Values for the total susceptibility index (TSI: 24 to
      48 h post-injection mortality + PHS mortality) following cellulose injections
      were higher for broilers reared at cool temperatures than at thermoneutral
      temperatures. The incidences of PHS induced by exposing broilers from different
      genetic lines to constant cool temperatures qualitatively paralleled the
      respective post-injection mortalities elicited by injecting the cellulose micro
      particle suspension into the same lines. These observations indicate the micro
      particle injection methodology potentially can replace unilateral pulmonary
      artery occlusion as the technique of choice for genetically selecting broilers
      that have a sufficiently robust pulmonary vascular capacity to resist the onset
      of pulmonary hypertension and PHS. The functional importance of the relative
      antigenicity of different micro-particle types, and the extent to which key
      immune-mediated responses, either beneficial or detrimental, might be co-selected
      by the micro-particle injection technology, remain to be clarified.

PMID- 12211315
TI  - Relative and absolute photorefractoriness in turkey hens: profiles of prolactin,
      thyroxine, and triiodothyronine early in the reproductive cycle.
AB  - An experiment was conducted to determine whether a commercial strain of turkey
      hens exhibits relative photorefractoriness (rPR) during a reproductive cycle and
      to ascertain whether plasma levels of certain hormones early in the reproductive
      cycle might be associated with subsequent expression of rPR or absolute
      photorefractoriness (aPR). Twenty-seven percent of hens maintained on a
      stimulatory photoperiod of 18L:6D for 19 wk and then given a shorter, but still
      stimulatory, photoperiod (13L:11D) ceased to lay and their ovaries regressed
      within 4 wk. These hens were considered rPR. Subsequent exposure to the 18L:6D
      photoperiod resulted in ovarian recrudescence in 41.7% of these PR individuals,
      confirming the presence of rPR at 19 wk after photostimulation. Absolute PR was
      observed in 15.1% of hens during a 27-wk reproductive season. Hens that became
      rPR or aPR exhibited significantly lower plasma prolactin levels at 8 and 14 wk
      after photostimulation than did hens that remained photosensitive (PS). Plasma
      levels of thyroxine were lower at 1 and 2 wk following photostimulation in hens
      that subsequently became PR than in hens that remained PS. We conclude that
      turkey hens may exhibit rPR and aPR during a reproductive cycle, whereas
      flockmates may remain PS for at least 27 wk. The presence of long daylengths,
      thyroid hormones, and PRL did not assure expression of PR. The expression of PR
      appears to be associated with reduced plasma throxine levels during a period when
      programming of PR is thought to occur and with reduced levels of prolactin
      following peak egg production.

PMID- 12211316
TI  - Pulmonary hypertensive response to endotoxin in cellulose-primed and unprimed
      broiler chickens.
AB  - Previous studies indicate that individual broilers vary widely in their pulmonary
      vascular responsiveness to i.v. injections of endotoxin. This individual
      variability may reflect differences acquired during previous respiratory
      challenges or genetic variability that may be associated with susceptibility to
      pulmonary hypertension syndrome (ascites). In the present study, we compared the
      endotoxin responses of 4- to 5- wk-old control broilers (unprimed) and broilers
      in which the pulmonary vasculature had been immunologically challenged 48 h
      previously by an i.v. injection of cellulose micro-particles (primed). The
      injected cellulose micro-particles are carried in the venous blood to the lungs,
      where they become trapped in the pulmonary vasculature and initiate acute focal
      inflammatory responses within the surrounding lung parenchyma. Physiological
      variables (respiratory rate, heart rate, pulmonary and systemic arterial
      pressures) were evaluated prior to and following the i.v. administration of 1 mg
      of Salmonella typhimurium endotoxin. Prior to endotoxin injection, the
      respiratory rate was higher in primed than in unprimed broilers; however, the
      heart rate, pulmonary arterial pressure, and systemic arterial pressure did not
      differ between groups. Broilers in both groups exhibited similar ranges of
      individual variability in their endotoxin responses. The overall time of onset,
      magnitude, and duration of the pulmonary hypertensive responses were similar for
      both groups. Accordingly, the initiation of a preexisting inflammatory response
      within the lung parenchyma did not alter the timing, amplitude, or variability of
      the subsequent pulmonary hypertensive response to endotoxin in broilers.

PMID- 12211317
TI  - Immunohistochemical evidence of cytochrome C oxidase subunit II involvement in
      pulmonary hypertension syndrome (PHS) in broilers.
AB  - Defects and variation in the relative amount of protein subunits in the
      mitochondrial electron transport chain (ETC) have been hypothesized to be
      involved, in part, in the pathogenesis of pulmonary hypertension syndrome (PHS),
      a costly metabolic disease. Thus, the major objective of this study was to
      determine whether differences in relative amounts of cytochrome c oxidase subunit
      I and II (COX I and II) can be detected by immunohistochemistry and digital image
      analysis in muscle tissue of broilers with PHS compared to control broilers.
      Cross sections of the breast muscle (pectoralis major) were stained with
      monoclonal antibodies for COX I and II. Relative areas of multiple microscope
      viewing fields (400x) per tissue section of COX I and II were quantified by
      counting immunopositive pixels on the digital images. Whereas the number of
      immunopositive pixels for COX II was higher in PHS birds compared to controls,
      there were no difference for COX I. The amount of COX II was positively
      correlated with the right to total ventricular weight ratio (RV:TV), suggesting
      that there may be increased expression of COX II associated with severity of
      pulmonary arterial hypertension. Thus, it is possible that COX II expression in
      PHS broiler may be involved in the pathogenesis of PHS.

PMID- 12211318
TI  - Effect of a short-term feed outage on broiler performance, live shrink, and
      processing yields.
AB  - This study was conducted to investigate the effect of a 12-h feed outage at
      various times prior to slaughter on subsequent broiler performance, live shrink,
      and processing yields. Broilers were full-fed or subjected to a 12-h feed outage
      followed by a refeeding period of 12, 24, or 48 h. Bird live weights or feed
      consumption was monitored during the outage and recovery periods. Birds were
      subjected to a 10-h feed withdrawal period and were slaughtered using simulated
      commercial conditions. Carcass weights were recorded through processing for yield
      determinations. The 12-h feed outage affected female broilers more than male
      broilers. Although all birds lost weight during their respective feed outage
      periods, birds were able to consume enough feed upon refeeding such that no
      significant differences in final live weight were detected at the initiation of
      feed withdrawal. Female broilers processed after a 12-h refeeding period had
      significantly larger gall bladders (by weight) as compared to the gall bladders
      of birds in the other treatments. Other processing parameters were not
      significantly affected by treatment. A 12-h feed outage and feed replacement
      prior to normal preslaughter feed withdrawal does not significantly affect
      processing yields, provided sufficient feed is replaced for at least 12 h prior
      to feed withdrawal. Because total feed consumption did not change following feed
      outage replacement, feed must be sufficient to compensate for that not consumed
      during the outage.

PMID- 12211319
TI  - Soaking turkey meat in salt-glucose syrup solutions--an experimental study of
      mass transfers.
AB  - Turkey meat can be salted and dried in one step by soaking in a concentrated salt
      glucose syrup solution at low temperature. Sugar impregnation is minimal; only
      low molecular weight sugars generally penetrate the product. Glucose uptake is
      very quick, suggesting the possible involvement of passive glucose transporters.
      The operational scope of this process, depending on the targeted end-product
      features, was determined for turkey meat on the basis of clearly characterized
      mass transport phenomena between the product and the soaking solution. With 2 cm
      thick meat fillets processed at 10 C it is thus possible to obtain salted-dried
      end-products containing 2 to 10% salt and 35 to 70% water, ranges that are
      compatible with a broad range of commercial cured products.

PMID- 12211320
TI  - Effect of antioxidants on the quality of irradiated sausages prepared with turkey
      thigh meat.
AB  - The effects of antioxidants on the flavor and color of electron-beam-irradiated
      turkey sausages were studied. Sausages were prepared from turkey thigh meat, NaCl
      (2.0%), phosphate (0.5%), water (10%), and one of five antioxidant treatments
      (none, vitamin E, sesamol, rosemary extract, or gallic acid at 0.02%). Sausages
      were stuffed and cooked in an 85 C smokehouse to an internal temperature of 74 C,
      then chilled and sliced to 1.5-cm thickness, and vacuum-packaged. Packaged
      sausages were randomly divided into three groups and irradiated at 0, 1.5 or 3.0
      kGy, using an electron beam. Volatiles, color, 2-TBA-reactive substances values,
      and sensory characteristics were analyzed. The antioxidant effect of sesamol was
      the highest, followed by vitamin E and gallic acid; rosemary extract had the
      weakest antioxidant effect. Irradiation induced red color in sausages, but
      addition of gallic acid, rosemary extract, or sesamol reduced it. Gallic acid was
      very effective in lowering the redness of irradiated and nonirradiated sausages.
      The redness (a*) values of sausages with added gallic acid that were irradiated
      at 0, 1.5, and 3.0 kGy were 1.49,2.03, and 2.29, respectively, whereas those of
      control sausages under the same irradiation conditions were 2.58, 2.81, and 3.25,
      respectively. The reduction of redness in irradiated sausages by antioxidants was
      not related to CO, because antioxidants had no effect on CO production by
      irradiation. The amount of total volatiles was decreased significantly by
      antioxidants, but antioxidants had minimal effect on the off-flavor of turkey
      sausages induced by irradiation.

PMID- 12211321
TI  - Culture and panic disorder: how far have we come?

PMID- 12211322
TI  - Panic probes and the identification of panic: a historical and cross-cultural
      perspective.
AB  - This article reviews the historical development of the category of panic disorder
      in the United States, particularly the shifting perspectives on both what causes
      panic and how the presence of panic should be determined. The notion that panic
      attacks of a panic-disorder type must be "out of the blue" and "unexpected,"
      except in the case of triggering by a particular place (i.e., agoraphobia), is
      critiqued. The authors illustrate that a meaningful epidemiological determination
      of panic rates in other cultural groups must be preceded by a detailed
      ethnography that ascertains the catastrophic cognitions, core symptoms, and
      typical cues of panic attacks in that particular context.

PMID- 12211323
TI  - Panic disorder, somatization, and the new cross-cultural psychiatry: the seven
      bodies of a medical anthropology of panic.
AB  - This article aims to adduce a framework that will allow for the cross-cultural
      study of panic disorder. The authors take sensation as the key unit of analysis,
      aiming to contribute to a medical anthropology of sensation. The seven analytic
      perspectives that are suggested in the article are the following: the full
      spectrum of panic attack sensations (the sensation body), the biological
      generation of panic sensations (the biological body), sensation as invoking an
      ethnophysiology (the ethnophysiological body), sensation as metaphor (the
      metaphoric body), sensation as invoking the landscape (the landscape body),
      sensation as invoking catastrophic cognitions (the catastrophic cognitions body),
      and sensation as invoking memory (the memory-associational body).

PMID- 12211324
TI  - Panic disorder in African-Americans: symptomatology and isolated sleep paralysis.
AB  - While attention has been paid to the study of panic disorder (PD) with or without
      agoraphobia among Caucasians, surprisingly little empirical research within the
      United States has looked at the phenomenology of PD among minority groups. In
      this paper we present data we have collected and review other research on the
      phenomenology, social supports, and coping behavior among African-Americans with
      panic disorder. Our studies indicate that, in comparison to Caucasians, African
      Americans with PD reported more intense fears of dying or going crazy, as well as
      higher levels of numbing and tingling in their extremities. African-Americans
      reported higher rates of comorbid post traumatic disorder and more depression.
      African-Americans also used somewhat different coping strategies (such as
      religiosity and counting one's blessings), less self-blame, and were somewhat
      more dissatisfied with social supports. The incidence of isolated sleep paralysis
      was, as per previous reports, higher in African-Americans. These findings,
      results of other research, and the implications for assessment and treatment are
      discussed within a semantic network analysis of panic (Hinton and Hinton 2002,
      this issue).

PMID- 12211325
TI  - Comparative phenomenology of ataques de nervios, panic attacks, and panic
      disorder.
AB  - This article examines a clinical sample of 66 Dominican and Puerto Rican subjects
      who reported ataques de nervios and also psychiatric disorder, and disentangles
      the phenomenological experiences of ataque de nervios, panic attacks, and panic
      disorder. In-depth cultural interviews assessed the symptomatic phenomenology of
      ataque episodes from the local perspective as well as in terms of key panic
      features, such as recurrence, rapid peaking of symptoms, and lack of provocation.
      Independent diagnostic assessments of panic attacks and disorder were also used
      to establish the phenomenological overlap between ataque and panic. Our findings
      indicate that 36 percent of ataques de nervios fulfill criteria for panic attacks
      and between 17 percent and 33 percent for panic disorder, depending on the
      overlap method used. The main features distinguishing ataques that fulfill panic
      criteria from ataques that do not include whether the episodes were provoked by
      an upsetting event in the person's life and the rapidity of crescendo of the
      actual attack. A key finding is that ataques often share individual
      phenomenological features with panic episodes, but that these features usually do
      not "run together" during the ataque experience. This confirms previous findings
      that ataque is a more inclusive construct than panic disorder. The importance of
      these findings for the clinical diagnosis and treatment of persons with ataques
      is discussed.

PMID- 12211326
TI  - Dizziness and panic in China: associated sensations of zang fu organ
      disequilibrium.
AB  - In China, distress is commonly experienced as dizziness that can develop into
      acute episodes resembling Western panic attacks. These distressing sensations
      occur in a unique cultural context with a distinctive set of associated symptoms,
      beliefs and purported etiologies. The experience of illness is informed by
      traditional Chinese medicine (TCM), an indigenous theory that elaborates a system
      of organ functioning called zang fi. Depending on the implicated zang fi organ
      disequilibrium, dizziness and panic present with a specific constellation of
      associated physical and mental symptoms. This paper presents a clinical survey of
      psychiatric disorders that demonstrates dizziness to be characteristic of Chinese
      anxiety states, most particularly panic. Three specific cases of dizziness
      focused panic ascribed to different states of zangfu disequilibrium are
      described. In a typical pattern, initial dizziness and associated symptoms
      intensify until they generalize into panic attacks. The degree of dizziness and
      panic corresponds to the state of disequilibrium of the zang fu organ system as
      well as instability of the social, interpersonal and environmental context of the
      patient. This paper elucidates the dynamic interpretants of dizziness in the
      Chinese context to contribute to a medical anthropology of this sensation.

PMID- 12211327
TI  - Panic attack in a context of comorbid anxiety and depression in a Tibetan
      refugee.

PMID- 12211328
TI  - A theoretical framework of ecological phase transitions for characterizing tree
      grass dynamics.
AB  - This paper describes a theoretical framework of ecological phase transitions for
      modeling tree-grass dynamics and analyzing the shifts or phase transitions from
      one vegetation structure to another in the southern Texas landscape. This
      framework implements the integration of percolation theory, fractal geometry and
      phase transition theory as a method for modeling the spatial patterns of tree
      grass dynamics, and nonlinear Markov non-equilibrium thermodynamic stability
      theory as a method for characterizing temporal tree-grass dynamics and phase
      transition. An historical sequence of aerial photographs at a Prosopis-thornscrub
      savanna parkland site in southern Texas was used to determine the parameters of
      the models. The preliminary analytical result accords well with current
      understanding and field survey of vegetation dynamics in the southern Texas
      landscape. The potential of such approaches and other relevant theories such as
      self-organized criticality and synergetics to vegetation dynamics is also
      discussed.

PMID- 12211329
TI  - A new method based on entropy theory for genomic sequence analysis.
AB  - We have refined entropy theory to explore the meaning of the increasing sequence
      data on nucleic acids and proteins more conveniently. The concept of selection
      constraint was not introduced, only the analyzed sequences themselves were
      considered. The refined theory serves as a basis for deriving a method to analyze
      non-coding regions (NCRs) as well as coding regions. Positions with maximal
      entropy might play the most important role in genome functions as opposed to
      positions with minimal entropy. This method was tested in the well-characterized
      coding regions of 12 strains of Classical Swine Fever Virus (CSFV) and non-coding
      regions of 20 strains of CSFV. It is suitable to analyze nucleic acid sequences
      of a complete genome and to detect sensitive positions for mutagenesis. As such,
      the method serves to formulate the basis for elucidating the functional
      mechanism.

PMID- 12211330
TI  - Egg distributions and the information a solitary parasitoid has and uses for its
      oviposition decisions.
AB  - Approximately three decades ago the question was first answered "whether
      parasitoids are able to assess the number or origin of eggs in a host" for a
      solitary parasitoid, Leptopilina heterotoma, by fitting theoretically derived
      distributions to empirical ones. We extend the set of different theoretically
      postulated distributions of eggs among hosts by combining searching modes and
      abilities in assessing host quality. In the models, parasitoids search either
      randomly (Poisson) (1) or by vibrotaxis (Negative Binomial) (2). Parasitoids are:
      (a) assumed to treat all hosts equally, (b) able to distinguish them in
      unparasitised and parasitised hosts only, (c) able to distinguish them by the
      number of eggs they contained, or (d) able to recognise their own eggs.
      Mathematically tractable combinations of searching mode (1 and 2) and abilities
      (a,b,c,d) result in seven different models (M1a, M1b, M1c, M1d, M2a, M2b and
      M2c). These models have been simulated for a varying number of searching
      parasitoids and various mean numbers of eggs per host. Each resulting
      distribution is fitted to all theoretical models. The model with the minimum
      Akaike's information criterion (AIC) is chosen as the best fitting for each
      simulated distribution. We thus investigate the power of the AIC and for each
      distribution with a specified mean number of eggs per host we derive a frequency
      distribution for classification. Firstly, we discuss the simulations of models
      including random search (M1a, M1b, M1c and M1d). For M1a, M1c and M1d the
      simulated distributions are correctly classified in at least 70% of all cases.
      However, in a few cases model M1b is only properly classified for intermediate
      mean values of eggs per host. The models including vibrotaxis as searching
      behaviour (M2a, M2b and M2c) cannot be distinguished from those with random
      search if the mean number of eggs per host is low. Among the models incorporating
      vibrotaxis the three abilities are detected analogously as in models with random
      search. Experiments with two species of solitary parasitoids (L. heterotoma and
      Asobara tabida) are conducted. All theoretically postulated distributions are
      separately fitted to the resulting experimental egg distributions. The AIC
      criterion is used to choose the best fitting theoretical distribution. For both
      parasitoid species the frequency distribution of best fitting models for
      experimental data is compared to the classification of distributions generated by
      simulations. This leads to the conclusion that both L. heterotoma and A. tabida
      are able to distinguish between parasitised and unparasitised hosts. For L.
      heterotoma the results point to an ability to assess the number of eggs in a
      host, whereas A. tabida does not seem to have this ability. This difference
      suggests that an egg is more valuable for L. heterotoma than for A. tabida.

PMID- 12211331
TI  - A brief history of R0 and a recipe for its calculation.
AB  - In this paper I present the genesis of R0 in demography, ecology and
      epidemiology, from embryo to its current adult form. I argue on why it has taken
      so long for the concept to mature in epidemiology when there were ample
      opportunities for cross-fertilisation from demography and ecology from where it
      reached adulthood fifty years earlier. Today, R0 is a more fully developed adult
      in epidemiology than in demography. In the final section I give an algorithm for
      its calculation in heterogeneous populations.

PMID- 12211332
TI  - Twenty-four-Hour blood pressure variability after acute ischemic stroke.
AB  - In people who are healthy, circadian rhythm in blood pressure is well
      established, with a 10% to 20% decrease in systolic and diastolic blood pressure
      during nighttime. Deviations correlate with target organ disease such as left
      ventricular hypertrophy, retinopathy, renal disease, and stroke. Little is known
      about blood pressure and circadian patterns in stroke patients. This study
      examined 13 patients hospitalized after ischemic stroke and monitored 24-hour
      blood pressure with ambulatory blood pressure monitors programmed tocollect
      readings every 30 minutes. All subjects had an abnormal pattern in blood pressure
      that did not dip during nighttime. Blood pressure load, a reported indicator of
      risk for target organ damage, was exceeded in all subjects during daytime and
      nighttime. Thus stroke patients are at high risk for target organ disease
      including recurrent stroke. Hypertensive management of stroke patients requires
      further investigation.

PMID- 12211333
TI  - Endotracheal suctioning: open versus closed with and without positive end
      expiratory pressure.
AB  - An open system of delivery of supplemental oxygen was compared with a closed
      system during endotracheal suction (ETS) at zero end-expiratory pressure (ZEEP)
      and 10 cm H2O positive end-expiratory pressure (PEEP). Four protocols in a 2 x 2
      design were administered in random order to 12 anesthetized and oleic acid
      injured animals. Statistically significant differences were found between
      protocols for arterial carbon dioxide tension (PaCO2), arterial oxygen saturation
      (SaO2), airway pressure (Paw), right atrial pressure (Pra), intrathoracic
      pressure (Pit), arterial pressure, and right ventricular afterload. Intrathoracic
      pressure and systolic aortic pressure differed between open and closed systems.
      Statistically significant differences between ZEEP and PEEP were found for PaCO2,
      SaO2, Paw, Pra, Pit, aortic pressure, and right ventricular afterload. Suctioning
      through a closed system made little difference in subject responses, but
      clinically significant differences existed when suctioning subjects on and off
      PEEP.

PMID- 12211334
TI  - National practice with assessment and monitoring of neuromuscular blockade.
AB  - The Food and Drug Administration, drug manufacturers, and critical care experts
      recommend using peripheral nerve stimulators (PNSs) to monitor depth of blockade
      when administering neuromuscular blocking agents (NMBAs). This study evaluates
      critical care nurses' practices regarding use of PNSs, identifies problems
      associated with their use, and determines other methods of assessing level of
      blockade to guide medication titration. Of respondents to a survey, 75% reported
      administering NMBAs for long-term use in their critically ill patients. In
      facilities using NMBAs, 63% monitored blockade level with aPNS. Because of
      practice disparities and monitoring problems, further education and research are
      needed to ensure adequate monitoring during NMBA administration.

PMID- 12211335
TI  - Heel ulcers in critical care units: a major pressure problem.
AB  - Identification and prevention of a heel ulcer in the critical care unit requires
      timely, systematic, and aggressive therapeutic interventions. Effective
      assessment, together with simple awareness of those at high risk for breakdown,
      can facilitate reduction in partial- and full-thickness injuries that later
      require extensive treatment measures and possible limb loss. This article
      provides current information regarding risk assessment tools, lower extremity
      assessment of perfusion and neuropathy, and guidelines for intervention.

PMID- 12211336
TI  - Critical care family members' satisfaction with bereavement experiences.
AB  - Heideggerian hermeneutics is used to illuminate the dialogues of 23 participants
      who experienced the death of a family member in the critical care unit within the
      past year. Those constructs that were considered helpful and satisfying during
      the process of losing the family member included information from the hospital
      staff, support from the family, and unrestricted visits. Those that were
      considered unhelpful and dissatisfying during the process of losing the family
      member included inaccessibility of the physician, cause of death, inadequate
      treatment, uncaring staff, and not being present at time of death. Constructs
      that were considered helpful and satisfying in the time since death were family,
      friends, and clergy. Those that were considered unhelpful and dissatisfying since
      death included legal/financial problems, dealing with bureaucracies, dealing with
      other bereaved family members, funeral homes, and organ donation.

PMID- 12211337
TI  - Family presence during CPR: new decisions in the twenty-first century.
AB  - At present, a great deal of controversy exists on whether family members should
      be allowed during the resuscitation of a loved one at a hospital. Literature
      reports that family presence is beneficial in some cases. However, other
      literature, in contrast, indicates this practice is not advantageous. This
      article discusses recent findings and explores pros and cons of family members'
      presence during cardiopulmonary resuscitation. Making this information available
      to health care personnel provides information for future dialogue.

PMID- 12211338
TI  - Thromboembolic disease and cancer: possible new treatments.
AB  - Hypoxia-induced endothelin (ET) and vascular endothelial growth or permeability
      factor (VEGF) play an important role in tumor biology by promoting angiogenesis.
      Angiogenesis alters hemostasis and promotes thromboembolic disease (TED).
      Therapeutic angiogenesis directed against ET and VEGF may reduce the incidence of
      TED in cancer patients.

PMID- 12211339
TI  - ERP implementation in rural health care.
AB  - Enterprise resource planning (ERP) systems provide organizations with the
      opportunity to integrate individual, functionally-oriented information systems.
      Although much of the focus in the popular press has been placed on ERP systems in
      large for-profit organizations, small hospitals and clinics are candidates for
      ERP systems. Focusing information systems on critical success factors (CSFs)
      allows the organization to address a limited number of areas associated with
      performance. This limited number of factors can provide management with an
      insight into dimensions of information that must be addressed by a system.
      Focuses on CSFs for small health-care organizations. In addition, also considers
      factors critical to the implementation of health-care information systems.
      Presents two cases. The results indicate support for the continuing use of CSFs
      to help focus on the benefits of ERPs. Focusing on groups of tangible and
      intangible benefits can also assist the rural health-care organization in the use
      of ERPs.

PMID- 12211340
TI  - Enhancing clinical and management discourse in ICT (information and communication
      technology) implementation.
AB  - Modern NHS organisations are seen to be increasingly reliant, in terms of
      achieving improvements and service targets, on the efficient provision of
      information to enable clinical, administrative and managerial decision making A
      key barrier to effective ICT introduction in NHS trust hospitals has been
      identified as the complex social, organisational and political issues endemic
      within the organisation, preventing true discourse amongst key stakeholders. This
      paper describes how the adaptation of critical social theoretical thinking may be
      used to develop an innovative approach to participative process and information
      flow modeling. This approach is used within a hospital trust to investigate its
      potential as a precursor to ICT procurement and development. Empirical results of
      the research are described with suggestions for a more informed approach to ICT
      introduction, leading to a re-examination of issues concerning: historical
      context, emancipatory practice and the role of the systems analyst.

PMID- 12211341
TI  - The deferrable elective patient: a means of reducing waiting-lists in
      orthopaedics.
AB  - The orthopaedic trauma session is almost universally adopted as a means of coping
      with non-elective orthopaedic demand Here patients who can be stabilised are
      treated in a weekday planned theatre session. It allows for greater consultant
      involvement and a reduction in out-of-hours operating. The utilisation of trauma
      theatre time is typically low. However, there is an opportunity to make better
      use of this time by including some "deferrable elective patients" in the session.
      These are elective patients who have been offered earlier treatment in return for
      accepting the possibility of postponement, if the trauma demand on the day of the
      appointment is high Simulation of patient demand was used to explore the balance
      between maximising the utilisation of the theatre sessions, avoiding too many
      overruns and ensuring a reasonable quality of care in a typical hospital in the
      UK.

PMID- 12211342
TI  - Management demands on information and communication technology in process
      oriented health-care organizations: the importance of understanding managers'
      expectations during early phases of systems design.
AB  - There are numerous challenges to overcome before information and communication
      technology (ICT) can achieve its full potential in process-oriented health-care
      organizations. One of these challenges is designing systems that meet users'
      needs, while reflecting a continuously changing organizational environment.
      Another challenge is to develop ICT that supports both the internal and the
      external stakeholders' demands. In this study a qualitative research strategy was
      used to explore the demands on ICT expressed by managers from functional and
      process units at a community hospitaL The results reveal a multitude of partially
      competing goals that can make the ICT development process confusing, poor in
      quality, inefficient and unnecessarily costly. Therefore, from the perspective of
      ICT development, the main task appears to be to coordinate the different visions
      and in particular clarify them, as well as to establish the impact that these
      visions would have on the forthcoming ICT application.

PMID- 12211343
TI  - A proposed approach for modelling health-care systems for understanding.
AB  - Discrete event simulation (DES) application is not as widely perceived as being
      useful for problem solving in the health-care arena as in other application
      areas. Suggests that this might be due to the way DES is applied in health-care
      modelling, as it follows a traditionally based-on-engineering approach This may
      not be a problem in itself; however, health-care systems are often complex in
      that they involve multiple decision-makers and thus understanding and
      communication between the various stakeholders are potentially problematic.
      Thinks that problem understanding and efficient communication tools largely
      contribute to the solution; consequently, proposes a modelling approach to
      enhance stakeholder understanding and communication. The approach is based on
      participation of stakeholders; it is also iterative rather than step-based. To
      demonstrate this approach, gives an example, aiming to show how this approach has
      been used successfully to facilitate the understanding process, concluding that
      involving stakeholders throughout not only helps them to understand their problem
      better, but also enables them to more fully appreciate the findings resulting
      from the model. This approach thus serves usefully to enrich the communication
      between the stakeholders.

PMID- 12211344
TI  - Clinical ICT systems: augmenting case management.
AB  - In order to improve the diagnosis and subsequent care given to patients, health
      care workers involved in the management of their care, as well as the treatment
      itself, are increasingly looking at the role that information and communication
      technologies (ICTs) can play in supporting the complex interactions between
      patient, doctor or nurse, consultant and medical equipment. Effective
      communication both amongst health-care workers and between health-care workers
      and their patients in both primary and secondary care is vital; ICTs can play an
      important role in this. In this paper possible interpretations given to the term
      "telemedicine" are discussed, and then attention is turned to the challenges
      involved in human interaction and the role of ICTs. An example of a clinical ICT
      system (AIDMAN) is used to illustrate how face-to-face interaction has usefully
      been supported by way of a "virtual" consultation, which facilitates remote
      medical diagnosis and can provide improved case management.

PMID- 12211345
TI  - Evaluation of the impact of a PACS system on an intensive care unit.
AB  - Describes part of a wider evaluation exercise undertaken to assess the impact of
      the introduction of a picture-archiving and communication system (PACS) on the
      adult intensive care unit (AICU) at the Royal Brompton NHS Trust in London. The
      objectives of this research were to evaluate the perceptions of PACS of the
      medical and ancillary staff working within AICU as well as to undertake a
      preliminary assessment of its impact on the workload of radiographers.
      Questionnaires, interviews and a process analysis were undertaken. The research
      findings indicate that the overall perception of staff towards the introduction
      of the PACS was positive. The impact of the system on the workload of
      radiographers was significant, reducing the time taken to obtain an image from 90
      to 60 minutes. However, lessons to be learned for future PACS implementations
      include the need to ensure compatibility with existing IT systems, adequate IT
      support and initiatives to ensure that the benefits of PACS are communicated to
      the hospital at large.

PMID- 12211346
TI  - Implementation of intelligent decision support systems in health care.
AB  - The full implementation of any intelligent system in health care, which is
      designed for decision support, has several stages, from initial problem
      identification through development and, finally, cost-benefit analysis. Central
      to this is formal objectivist evaluation with its core component of inherent
      performance of the outputs from these systems. A Medline survey of one type of
      intelligent system is presented, which demonstrates that this issue is not being
      addressed adequately. Lack of criteria for dealing with the outputs from these
      "black box" systems to prescribe adequate levels of inherent performance may be
      preventing their being accepted by those in the health-care domain and, thus,
      their being applied widely in the field.

PMID- 12211347
TI  - Using geographical information systems for management of back-pain data.
AB  - In the medical world, statistical visualisation has largely been confined to the
      realm of relatively simple geographical applications. This remains the case, even
      though hospitals have been collecting spatial data relating to patients. In
      particular, hospitals have a wealth of back pain information, which includes pain
      drawings, usually detailing the spatial distribution and type of pain suffered by
      back-pain patients. Proposes several technological solutions, which permit data
      within back-pain datasets to be digitally linked to the pain drawings in order to
      provide methods of computer-based data management and analysis. In particular,
      proposes the use of geographical information systems (GIS), up till now a tool
      used mainly in the geographic and cartographic domains, to provide novel and
      powerful ways of visualising and managing back-pain data. A comparative
      evaluation of the proposed solutions shows that, although adding complexity and
      cost, the GIS-based solution is the one most appropriate for visualisation and
      analysis of back-pain datasets.

PMID- 12211348
TI  - Managing managed care: the enabling role of IS/IT.
AB  - In their conceptualization of the principal/agent relationship, Jensen and
      Meckling were not referring to a knowledge worker (KM) agent. Agency theory is
      extended to the context of a KW agent to identify a key role for IS/IT in
      facilitating the monitoring function. To test this, the dynamics of a critical
      principal-KW agent relationship in the health-care industry are investigated It
      is demonstrated that IS/IT goes beyond just alleviating the agency problem to
      enabling the KW agent to perform "self-monitoring". The results are significant
      for health care, agency relationships and the use of IS/IT with knowledge
      workers.

PMID- 12211349
TI  - Clinical and experimental studies of autoimmune inner ear disease.
AB  - Otolaryngologists have long sought to identify causes of sensorineural hearing
      loss that could be reversed by medical treatment. An increasing amount of
      clinical and experimental evidence indicates that this postulated entity is
      related to autoimmune inner ear disease. Because of the lack of well-defined
      detection methods for identifying autoimmune processes within the human inner ear
      and the fact that it is one of the few organs of the body not amenable to
      diagnostic biopsy there has been great interest in developing animal models that
      mimic clinical entities. Different models will be presented in this paper. The
      results of these studies should provide sufficient evidence to establish a clear
      position in mainstream immunology for the entity of autoimmune inner ear disease.

PMID- 12211351
TI  - Hearing loss evaluation of Sjogren's syndrome using distortion product
      otoacoustic emissions.
AB  - Sjogren's syndrome (SS) is a cell-mediated immune disorder primarily affecting
      the exocrine glands and hearing loss may be the first otological manifestation of
      this autoimmune disease. In order to assess the degree of sensorineural hearing
      loss in SS, 22 female patients were examined by means of standard audiometric
      tests (pure-tone audiometry, acoustic reflexes and impedance testing) and using
      distortion product otoacoustic emissions (DPOAEs). The results indicated that
      only 36.3% of the patients had mild sensorineural hearing loss. Hearing level and
      distortion product threshold estimates were found to be significantly correlated.
      No relationship was found between the duration of the disease and the DPOAE and
      hearing threshold variables. The data suggest that SS may not directly cause
      sensorineural hearing loss.

PMID- 12211350
TI  - Cochlear function in ears with immunomediated inner ear disorder.
AB  - The aim of the present study was to evaluate the performance of ears with inner
      ear disorder, responsive to immunosuppressive drugs, in advanced tests designed
      to assess primary cochlear functions (temporal integration, frequency
      selectivity, cochlear mechanics). The results of this study suggest that
      immunomediated inner ear disease results, in the acute clinical stage, in the
      development of endolymphatic hydrops, which increases the stiffness of the
      vibrating structures within the inner ear and causes dysfunctions of the outer
      hair cells. Our patients presented with upsloping or flat sensorineural hearing
      loss, absence of evoked otoacoustic emissions and distortion-product otoacoustic
      evoked emissions and abnormal temporal integration, frequency selectivity and
      cochlear mechanics. Following immunosuppressive treatment, hydrops recovered,
      hearing subsequently returned to normal, the audiometric curve became flat at low
      to-middle frequencies and primary cochlear function tended to normalize. This
      study seems to support the usefulness of testing primary cochlear functions in
      order to monitor the clinical course of immunomediated inner ear disorders.

PMID- 12211352
TI  - Human leukocyte antigen-A, -B, -C and -DR alleles and soluble human leukocyte
      antigen class I serum level in Meniere's disease.
AB  - Previous studies have suggested that many human leukocyte antigen (HLA)-A, -B, -C
      and -DR alleles are associated with Meniere's disease (MD), an inner ear disorder
      with a proposed autoimmune etiopathogenesis. Despite some discrepancies many
      reports are in agreement with a hypothesis suggesting an influence of
      serologically detected HLA-C products in the susceptibility to the disease. To
      confirm these data we investigated the distribution of HLA-A, -B, -C and -DR
      antigens that well define the HLA polymorphism using DNA typing. Furthermore, as
      autoimmune factors have been claimed to play a role in MD, we investigated the
      serum level of soluble HLA class I (sHLA-I). Molecular typing of HLA class I and
      II was performed using polymerase chain reaction sequence-specific primers in 41
      patients affected by MD, 34 patients affected by other inner ear diseases (OIDs)
      and 101 healthy subjects. An ELISA technique was employed to investigate the
      serum level of sHLA-I in 17 MD patients, 10 OID patients and 83 healthy subjects.
      The results showed a significantly increased frequency of the Cw*07 specificities
      in MD patients when compared to OID patients (63.4% vs 32.3%; p = 6.9 x 10(-3);
      relative risk [RR] = 3.6) and healthy subjects (63.4% vs 35.6%; p = 2.28 x 10(
      3); RR = 3.1). The sHLA-I concentrations detected in sera did not differ
      significantly between MD patients (616 +/- 271 ng/ml), OID patients (570 +/- 307
      ng/ml) and healthy subjects (518 +/- 340 ng/ml).

PMID- 12211353
TI  - Molecular mechanism of autoimmune hearing loss.
AB  - Molecules considered as autoantigens in autoimmune sensorineural hearing loss and
      Meniere's diseases are type II collagens, type IX collagens, 30 kD proteins of
      inner ear membranes, laminin, 68 kD proteins of inner ear, PO protein, Raf I
      protein and beta-tubulin are reviewed in relation to molecular mechanisms of
      autoimmune injury of inner ear resulting in hearing loss.

PMID- 12211354
TI  - Autoimmunity in sudden sensorineural hearing loss: possible role of anti
      endothelial cell autoantibodies.
AB  - In order to verify whether anti-endothelial cell autoantibodies (AECAs) can be
      used as serological markers of inner ear vasculitis in sudden sensorineural
      hearing loss (SSHL), 32 patients affected by idiopathic SSHL were investigated.
      All patients underwent a routine general physical examination and extensive
      audiovestibular, microbiological and immunological investigations. Fourteen
      normal subjects without a history of HL, autoimmune or metabolic disease served
      as controls. Detection of AECAs was performed using an indirect
      immunofluorescence technique. AECA-positive patients were treated with
      methylprednisone, while AECA-negative patients were treated with a combined
      regimen of steroids, plasma expander and aspirin. The average hearing recovery
      for 5 frequencies (0.25-4 kHz) was analyzed in each subject 1 month after
      treatment and every 3 months thereafter; median follow-up was 12 months (range 9
      18 months). A total of 15/32 patients (46.8%; 11/19 females, 4/13 males) were
      AECA-positive and thus differed significantly from the normal population in whom
      only 2/14 tested cases were positive (p = 0.03). Severe hearing loss was
      associated with being AECA-positive in 8/11 cases. During follow-up, 25/32
      patients improved their hearing and 17 of these patients were AECA-negative. The
      seven cases without hearing improvement were all AECA-positive. In patients with
      SSHL, immune-mediated vascular damage may have a pathogenetic role and AECAs may
      represent a serological marker of vasculitis even if they are not inner ear
      specific and even if they represent an epi-phenomenon rather than the only cause
      of SSHL.

PMID- 12211355
TI  - Use of mammalian inner ear antigens for the diagnosis of autoimmune sudden loss
      of vestibular function.
AB  - It has been postulated that bilateral sensorineural hearing loss (SNHL) may be
      the result of an ongoing autoimmune process against the inner ear and a pattern
      of progressive bilateral SNHL linked to an autoimmune inner ear disorder has been
      reported. Various attempts have been made to develop an assay to confirm the
      diagnosis of autoimmune inner ear disease. In this study we used a Western blot
      assay to determine the presence of IgG antibodies directed against a PO antigen
      (30 kDa) of the guinea pig in the sera of patients affected by sudden loss of
      vestibular function (SLVF). Ten patients affected by vestibular neuritis were
      enrolled: eight with unilateral vestibular loss and two with sequential bilateral
      impairment. We also tested nine patients with sudden unilateral hearing loss,
      five with benign paroxysmal positional vertigo and six normal subjects. In the
      present study only one patient, a woman affected by bilateral vestibular
      impairment, had IgG antibodies against the PO protein. Our results indicate
      either that the antigen PO is not a valid marker for autoimmune unilateral SLVF
      or that our patients did not have an immunological basis for their disease.
      However, we can suggest that bilateral impairment of vestibular function and
      bilateral progressive SNHL are more likely to be immune-mediated disorders and
      that PO could be a valid marker for these diseases. As bilateral vestibular
      neuritis is an uncommon disease, a multicentre study is required to confirm our
      suggestions.

PMID- 12211356
TI  - Immune-mediated hearing loss: basic mechanisms and options for therapy.
AB  - Immune responses are an important component of the defense of the inner ear
      against infection. However, immunity appears to be restricted in the labyrinth,
      as the inflammation associated with immune responses can damage the delicate
      cellular structures that mediate hearing and balance. When immunoregulation is
      compromised, either experimentally or through disease, immune-mediated inner ear
      damage and hearing loss can result. Because there are few resident leukocytes
      within the labyrinth, immunity and inflammation are mediated primarily by cells
      that enter the inner ear following the activation of post-capillary venules,
      which in the cochlea are the spiral modiolar veins. Activated lymphocytes are an
      important component of the infiltrating leukocytes, and their interactions with
      antigen mediate inner ear immunity. While evidence of autoimmunity specific to
      the inner ear is incomplete, an autoimmune origin is often suspected in
      idiopathic, bilateral, rapidly progressive hearing loss. Systemic
      immunosuppressive drugs can be effective in reversing such hearing loss, although
      at the cost of occasionally severe side-effects. Experimental evidence suggests
      that local therapy may be effective in treating this condition, if it were to
      target the infiltration of leukocytes into the labyrinth.

PMID- 12211357
TI  - Cochlear implants in systemic autoimmune vasculitis syndromes.
AB  - The concept that autoimmunity may damage the inner ear was introduced by McCabe
      in 1979. Audiovestibular symptoms may occur in isolation or may be mediated by
      vasculitis in patients affected by systemic autoimmune disorders. Sensorineural
      hearing loss (SNHL) is typical in Cogan's syndrome but occurs less frequently in
      Bechet's syndrome and in systemic necrotizing vasculitides. Patients affected by
      immune-mediated profound SNHL represent ideal candidates for cochlear
      implantation as these patients become deaf after years of hearing. The disease
      itself and the medication taken may, however, influence the prognosis of cochlear
      implantation in these patients. We retrospectively evaluated the pre- and
      intraoperative findings as well as the postoperative course and performance of a
      group of five patients affected by a systemic vasculitis syndrome who received a
      cochlear implant. Implantation was successful in all patients, no complications
      occurred and excellent postoperative speech perception was achieved. We conclude
      that cochlear implantation in patients affected by immune-mediated inner ear
      disorders is effective although the long-term results remain to be evaluated.

PMID- 12211358
TI  - Parent figure transitions and delinquency and drug use among early adolescent
      children of substance abusers.
AB  - Children of substance abusing parents have an elevated risk for experiencing
      disruptions in household composition and for engaging in problem behaviors. This
      study investigated whether multiple parent figure transitions predicted the
      likelihood of delinquency and drug use among a sample of early adolescents with
      parents receiving methadone treatment for opiate addiction. Controlling for
      baseline delinquency, child characteristics, family conflict, parental
      depression, and parent criminal history, a greater number of parenting
      disruptions during the longitudinal study period was associated with a higher
      probability of delinquent behavior. Gender moderated the effect of parent figure
      transitions in a parallel analysis for drug use. After accounting for baseline
      drug use and potentially confounding factors, only adolescent females had a
      higher likelihood of drug use as the number of family disruptions increased. In
      contrast, age was strongly associated with drug use for males. A subgroup of
      youths who experienced tremendous family instability and had no single consistent
      parent figure during the study period were at extreme risk for delinquent
      behavior. The findings are interpreted in terms of cumulative stress resulting
      from multiple parenting disruptions over time and differential influences on the
      expression of problem behaviors depending on gender.

PMID- 12211359
TI  - Vulnerability factors for homelessness associated with substance dependence in a
      community sample of homeless adults.
AB  - We studied a community probability sample of 1185 homeless individuals to examine
      substance dependence in relationship to other personal and social vulnerabilities
      linked to homelessness, including sociodemographics, childhood/adolescent
      factors, prehomelessness factors, multiple episodes of homelessness, and the
      quality of shelter in their current episode of homelessness. These vulnerability
      factors were significantly concentrated in homeless individuals with lifetime and
      recent substance dependence, especially among those with both alcohol and drug
      dependence. In addition, the profiles of the homeless with alcohol dependence
      alone were distinct from those with drug dependence alone or both, with older
      age, more males, longer histories of homelessness, and significantly poorer
      quality shelter during the previous 30 days. Therefore, homeless individuals with
      substance dependence have many vulnerabilities beyond their substance dependence
      that should be dealt with in treatment or other service settings before lasting
      housing can be achieved.

PMID- 12211360
TI  - Gender differences in HIV risk behaviors among young injectors and their social
      network members.
AB  - Using epidemiological and social network research methods, this study examines
      gender differences in HIV risk and protective behaviors and social network
      characteristics among 193 young injection drug users (IDUs) and 127 referred
      members of their social networks. Respondents reported on their drug use, sexual
      behavior, and relationships within three types of social networks: hang out
      (i.e., friendship); drug use; and sexual networks. Most respondents were homeless
      and had experienced numerous life stressors. Females' social networks consisted
      more predominantly of drug injectors, and members more frequently appeared
      multiple networks. Females reported needle sharing more frequently than males,
      but also reported more protective behaviors such as needle exchange use and
      carrying clean syringes. Young female IDUs may compound their risk by having sex
      and injecting with higher risk partners. However, their propensity to practice
      protective behaviors may provide an opening for interventions to reduce their HIV
      risk and that of their social network members.

PMID- 12211361
TI  - Lifetime inhalant use among alternative high school students in Texas: prevalence
      and characteristics of users.
AB  - This cross-sectional study describes the prevalence of lifetime inhalant use and
      identifies demographic, psychosocial, and other risk behavior characteristics of
      students reporting lifetime inhalant use. The sample consisted of 354 students
      attending alternative high schools (dropout prevention/recovery schools) in
      Texas. The prevalence of lifetime inhalant use was 27.7%. After controlling for
      potentially confounding factors, students reporting lifetime inhalant use were
      less likely to be financially supported by their parents/guardians, more likely
      to use alcohol/tobacco, marijuana, and cocaine, and more likely to carry weapons
      and consider suicide. Study results may allow school officials, parents,
      researchers, and health care providers to gain a better understanding of inhalant
      use among students at risk for dropping out of school, a group which has not been
      extensively studied by previous researchers.

PMID- 12211362
TI  - Health services utilization by injection drug users participating in a needle
      exchange program.
AB  - OBJECTIVE: To determine the characteristics associated with health care and drug
      treatment utilization among a distinctly high-risk sub-population of injectors
      participating in a needle exchange program (NEP). METHODS: Between June 1998 and
      May 1999, study staff collected demographic and health services utilization data
      on participants of the Baltimore NEP. Odds ratios and logistic regression were
      used to identify the participant characteristics associateds with utilizing
      primary health care and drug treatment during the prior 3 years. RESULTS: Among
      269 participants, 81% were African-American and 66% were male. Over half (56%)
      had not graduated from high school, 89% were unemployed, 70% did not have health
      insurance, and the median age was 39 years. Fifty-eight percent of the
      participants reported utilizing primary care (i.e., visited a physician or other
      health care provider) and 44% had utilized drug treatment during the prior 3
      years. Primary care utilization was associated with age > or = 39 [adjusted odds
      ratio (AOR) = 1.82], having health insurance (AOR = 2.16), and exchanging a
      higher volume of syringes per NEP visit (AOR = 2.45). Recent drug treatment
      utilization was associated with African-American race (AOR = 0.41), unemployment
      (AOR = 2.72), having health insurance (AOR = 2.05), and exchanging a higher
      volume of syringes per NEP visit (AOR = 0.60). CONCLUSIONS: Health insurance was
      significantly associated with the recent utilization of both primary care and
      drug treatment, yet only one-third of NEP attenders were insured. Facilitating
      the uptake of health insurance services at NEP sites may improve the access to
      health care for drug users who are currently not utilizing the health care
      system.

PMID- 12211363
TI  - Responses to a drug and alcohol problem assessment for primary care by ethnicity.
AB  - Differences in responses by ethnic group to The Drug Abuse Problem Assessment for
      Primary Care (DAPA-PC) were examined. The DAPA-PC is a self-administered (via
      computer), internet-based screening instrument with automatic scoring, patient
      profile for medical reference, and unique motivational messages. Results indicate
      differences between blacks and whites on responses to several items in these
      instruments. Differences in drug use were also found between the two ethnic
      groups in hair/urine results. The screening criteria for the DAPA-PC instrument
      appear to work for both the groups in this study. Differences in responses to
      alcohol and drug screening instruments by ethnic group should be taken into
      consideration when designing screening instruments for alcohol and/or other drug
      use and these instruments should be adapted for different ethnic groups, when
      necessary. The results of this study suggest that the DAPA-PC instrument is a
      useful alcohol and drug abuse screening instrument for both the blacks and whites
      in a primary care population.

PMID- 12211364
TI  - Alcohol use among out-of-treatment crack using African-American women.
AB  - OBJECTIVE: The purpose of this study was to categorize the quantity and frequency
      of alcohol use among African-American women who were abusing crack cocaine and to
      explore relationships between categories of alcohol use and demographic
      variables, cocaine use, comorbidity, and risky sexual behaviors. METHOD: Data
      were collected from 635 out-of-treatment crack cocaine-abusing African-American
      women in the Raleigh/Durham area of North Carolina. The women were categorized as
      light (n = 272), moderate (n = 216), or heavy drinkers (n = 147). RESULTS: Women
      classified as heavy drinkers were demographically similar to light and moderate
      drinkers. Heavy drinkers used more crack cocaine and were more likely to engage
      in sexual risk behaviors than were the other two drinking groups. The heavy
      drinkers also reported greater psychological distress, and they were more likely
      to report histories of physical, sexual, and emotional abuse. CONCLUSIONS: Heavy
      alcohol use among crack-abusing African-American women may be a marker for a host
      of underlying problems that require special attention. The HIV prevention
      programs and substance abuse treatment programs that provide services to crack
      abusing women should screen for heavy drinking. Women identified as heavy
      drinkers should undergo more in-depth assessments and receive additional
      referrals as appropriate.

PMID- 12211365
TI  - Commentary on why national epidemiological estimates of substance abuse by race
      should not be used to estimate prevalence and need for substance abuse services
      at community and local levels.
AB  - Large-scale epidemiological studies suggest substantially lower prevalence rates
      of substance abuse disorders in Black Americans than in White Americans. This is
      counterintuitive since indicators of socioeconomic status, which on an average
      are lower in Blacks than Whites, are inversely associated with the prevalence of
      psychiatric disorders. Herein, we recommend against the use of race-specific
      national epidemiological data to estimate prevalence of substance abuse disorders
      and need for services at community/local levels. This is important so that
      catchment areas with high proportions of minorities receive equitable levels of
      substance abuse prevention and treatment resources. We illustrate our
      recommendation through observations and potential biases (e.g., reporting bias)
      identified from large-scale epidemiological studies of the prevalence of
      substance use disorders between Black and White Americans.

PMID- 12211366
TI  - The heritability of alcohol abuse and dependence: a meta-analysis of behavior
      genetic research.
AB  - A meta-analysis was performed on 50 family, twin, and adoption studies in which
      problem drinking and alcohol dependence served as the primary criterion measure.
      The results showed that far from being an established "fact," the genetic
      foundations of alcohol misuse are modest and heterogeneous. A weighted mean phi
      effect size of 0.12 (95% Confidence Interval = 0.11-0.12) was obtained for the
      total sample of 72 effect sizes. Four potential moderator variables (proband
      gender, sample nationality, pattern severity, year of publication) were examined
      with outcomes confirming that the heritability of alcohol misuse is stronger in
      males and in studies employing more severe definitions of abuse (alcoholism,
      alcohol dependence). When the effect size measure was restricted to studies using
      male subjects with more severe diagnoses of alcohol misuse, the unweighted mean
      phi effect size was only 0.18 (95% Confidence Interval = 0.15-0.21), with an even
      smaller weighted mean phi effect size of 0.15 (95% Confidence Interval = 0.12
      0.18); results which indicate an upper limit of 30-36% for the heritability of
      alcohol misuse.

PMID- 12211367
TI  - Effects of selection for ultrasound intramuscular fat percentage in Angus bulls
      on carcass traits of progeny.
AB  - Angus bulls (n = 20) from three pure-bred herds in Georgia were acquired to
      determine the impact of selecting sires based on phenotypic yearling ultrasound
      intramuscular fat percentage (UIMF) or UIMF EPD on marbling score of steer
      progeny. Each year in each herd, pairs of bulls were selected to create large
      differences based on their age adjusted phenotypic yearling UIMF measurements.
      The average UIMF, weighted by number of progeny per sire, was 3.75% (SD = 1.10%)
      and 1.70% (SD = 0.53%) for high UIMF (HU) and low UIMF (LU) bulls, respectively.
      All available ultrasound measurements collected in the purebred co-operator herds
      were combined with other ultrasound records collected by the American Angus
      Association for the computation of genetic values for ultrasound fat thickness,
      ribeye area, and intramuscular fat percentage. Each year bulls were randomly
      mated to 14 to 30 commercial Angus females. Carcass weight, fat thickness at the
      12th rib, ribeye area at the 12th rib, marbling score, yield grade, and quality
      grade measurements were collected on 188 steer progeny. Carcass data were
      linearly adjusted to 480 d of age at slaughter. Steer progeny sired by HU bulls
      had higher age-adjusted marbling score and quality grade (P < 0.05), and smaller
      age-adjusted ribeye area (P < 0.05) than steer progeny sired by LU bulls. No
      significant differences between phenotypic UIMF lines were found for age-adjusted
      fat thickness (P = 0.84) and yield grade (P = 0.33) in the steer progeny. The
      regression of age-adjusted carcass marbling score and quality grade of the steer
      progeny on ultrasound intramuscular fat percentage EPD of the sires produced
      highly significant regression coefficients of 90.50 and 49.20, respectively.
      Thus, yearling Angus bulls selected for high-phenotypic UIMF and UIMF EPD can be
      expected to produce steer progeny with significantly higher amounts of marbling
      and quality grade. It also appears that marbling can be increased without
      corresponding increases in external fat thickness and yield grade.

PMID- 12211368
TI  - Effects of supplementation with high linoleic or oleic cracked safflower seeds on
      postpartum reproduction and calf performance of primiparous beef heifers.
AB  - Primiparous Angus x Gelbvieh (n = 36) rotationally crossed beef cows (initial BW
      = 487.9 +/- 10.5 kg, body condition score = 5.5 +/- 0.02) were utilized to
      determine effects of supplemental safflower seeds high in linoleic (76% 18:2) or
      oleic (72% 18:1) acid on cow BW change, body condition score, milk production and
      composition, calf weight gain, cow serum metabolites, and metabolic hormones. On
      d 3 postpartum, cows were randomly assigned to one of three isonitrogenous
      dietary supplements with equal total quantity of TDN: corn-soybean control
      supplement (n = 12); high-linoleate safflower seeds (n = 12); or high-oleate
      safflower seeds (n = 12). Safflower-seed supplements were formulated to provide
      5% DMI as fat. Supplements were individually fed from d 3 postpartum through 90 d
      postpartum. Cows had ad libitum access to native grass hay (7.8% CP), trace
      mineralized salt, and water. Date of parturition was evenly distributed across
      treatments with all cows calving within 14 +/- 0.8 d. There were no differences
      (P = 0.65) in total OM intake among treatments. Although cow BW change did not
      differ (P = 0.33) by treatment, supplementation influenced cow body condition
      score (P = 0.02) with linoleate-supple-mented cows in higher (P = 0.005)
      condition overall than oleate-supplemented cows (5.1 +/- 0.06 vs 4.9 +/- 0.06).
      Twenty-four-hour milk production did not differ (P = 0.68) among treatments.
      Percentage milk fat was not different at d 30; however, at d 60 and d 90
      percentage milk fat was greater (P ( 0.05) in control and oleate-supplemented
      cows than in linoleate-supplemented cows. Calf BW gains (P = 0.27) and adjusted
      205-d weights (P = 0.48) were not affected by supplement treatment.
      Supplementation did not influence serum concentrations of glucose (P = 0.38),
      NEFA (P = 0.61), GH (P = 0.29), IGF-I (P = 0.81), insulin (P = 0.26), or IGF-I
      binding proteins (P > or = 0.11). Days to conception did not differ (P = 0.40)
      among treatments. Although overall productivity of the primiparous cows and their
      calves was not altered by safflower-seed supplementation, differential effects
      were noted between supplements. Oleate supplementation increased percentage milk
      fat at d 60, and cow body condition score was lower than in linoleate
      supplemented cows. Linoleate-supplemented cows had greater body condition scores
      by 90 d postpartum than either corn-soybean- or oleatesupplemented cows.

PMID- 12211369
TI  - Weight necessary to change body condition scores in Angus cow.
AB  - Weights and body condition scores (BCS) were measured and assessed on Angus
      females (n = 367) over 14 yr (1981 to 1994) to allow calculation of weight
      adjustments for different BCS. Data were collected at five time periods:
      prepartum, postpartum, prebreeding, postbreeding, and midgestation. Individual
      cows with multiple records were included in the analysis as repeated measures to
      yield 3,912 total observations. Body condition score was assigned on a scale of 1
      = emaciated to 9 = obese. Only BCS 2 through 8 were analyzed, as there were zero
      recorded observations of BCS 1 or 9. The final model included age and the time
      period by BCS interaction as fixed effects. Year by animal within age interaction
      and a residual error term were treated as random effects. Animal was included to
      correct for repeated measures across time periods and years for individual
      animals. All these effects were significant (P < 0.0001). Weight adjustments for
      BCS were calculated for each time period. Cow weight and weight adjustments for
      BCS were not consistent for each time period. Overall weight adjustments to
      adjust cows to BCS of 5 were (kg +/- SEM) BCS = 2 (68 +/- 12), BCS = 3 (50 +/-
      4), BCS = 4 (21 +/- 1), BCS = 5 (0), BCS = 6(-24 +/- 2), BCS = 7(-51 +/- 3), and
      BCS = 8 (-73 +/- 7).

PMID- 12211370
TI  - Relationships between body weight at first mating and subsequent body
      development, feed intake, and reproductive performance of rabbit does.
AB  - A retrospective study was performed to evaluate the relationships between BW at
      first insemination and subsequent body development, feed intake, reproductive
      performance, and culling rate of rabbit does. Young rabbit does are vulnerable to
      body energy deficit in first lactation, resulting in decreased reproductive
      performance and high replacement rate. Heavy does at first insemination might be
      able to benefit from the extra amount of BW to cope with the energy deficit
      during first lactation. Data of three experiments were used in which does were
      given ad libitum access to feed during rearing and inseminated at 14.5 wk of age.
      The first two parities of each doe were recorded. Does were categorized in three
      groups based on their BW at 14.5 wk of age (first insemination): heavy (BW > or =
      4,000 g), medium (BW 3,500 to 4,000 g), and small (BW < 3,500 g). Among does that
      kindled, differences in BW at first insemination were related to differences in
      voluntary feed intake and body growth rate during rearing. Heavy does consumed
      more feed per day (+ 45 g/d, P < 0.001) and had a higher BW gain (+ 12 g/d, P <
      0.001) than small does from weaning (4.5 wk) to 14.5 wk of age. Body weight at
      first insemination did not affect BW, feed intake, and culling rate during the
      first two parities. Heavy does were heavier at first insemination and remained so
      throughout the reproductive period, but they followed a similar BW curve as
      medium and small does. A higher BW at first insemination (14.5 wk of age)
      improved litter size in the first parity (8.9, 7.7, and 6.4 for heavy, medium,
      and small does, respectively, P < 0.05). Extra BW at start of reproduction
      improves litter size in the first parity but does not contribute to an improved
      feed intake or increased BW development during reproduction.

PMID- 12211371
TI  - Shade effects on performance, carcass traits, physiology, and behavior of heat
      stressed feedlot heifers.
AB  - To determine whether shade influences performance, carcass traits, immunology,
      respiration rate, and behavior of cattle under conditions similar to those in
      commercial feedlots, we used 168 heifers in 12 soil-surfaced pens. Six pens were
      shaded with a galvanized steel-roofed shade (approximately 4 m high), allowing
      for 2.12 m2 of shade/heifer, and six pens served as the unshaded control. Heifers
      were fed a 90% concentrate diet during the 121-d trial that began in mid-June,
      performance variables (DMI, BW, ADG, gain:feed) were measured, and dietary
      concentrations of NEm and NEg calculated from performance data. A blood sample
      was collected to assess immune measures. Respiration rates and behaviors
      (feeding, drinking, walking, standing, lying, agonistic, and bulling) also were
      measured during the study. Carcass data (yield grade, kidney, pelvic, and heart
      fat, longissimus muscle area, hot carcass weight, quality grade, liver abscess
      rate, and incidence of dark-cutting beef) were collected at slaughter. Shaded
      heifers had higher (P < 0.05) DMI, ADG, and final BW than unshaded heifers. The
      gain:feed ratio and calculated dietary NEm and NEg concentrations did not differ
      (P > 0.26) between treatments. Most carcass traits did not differ between
      treatments, but more (P < 0.02) carcasses ofheifers in shaded pens graded USDA
      Choice than those in unshaded pens, which resulted primarily from the incidence
      of dark cutters being decreased (P < 0.04) by approximately half in carcasses
      from shaded compared with unshaded heifers. Respiration rate and percentage of
      circulating neutrophils were decreased (P < 0.01) for shaded compared with
      unshaded heifers. The treatment x time of day effect was significant (P < 0.05)
      for all behavioral measurements. Shaded heifers spent more time laying down
      (0800, 1200, and 1500, P < 0.05) and less time standing (1200 and 1500, P < 0.05)
      than unshaded heifers. Agonistic behavior was less (P < 0.05) for shaded than for
      unshaded heifers at 1900 and 2000, and bulling was less (P < 0.05) for-shaded
      than unshaded heifers at 2100. Results suggest that shade improved performance
      and altered behavior by feedlot heifers during the summertime in West Texas.

PMID- 12211372
TI  - Nutrient composition of Kansas swine lagoons and hoop barn manure.
AB  - A total of 312 samples in two experiments were analyzed to determine mean
      nutrient concentrations of swine lagoons and hoop barns in Kansas. First, in a
      retrospective study (Exp. 1), we obtained 41 sample analyses from the Kansas
      Department of Agriculture of sow, nursery, wean-to-finish, finish, and farrow-to
      finish operations in 1999. The average total N concentration was 899 ppm (SD =
      584 ppm), while the total P concentration was 163 ppm (SD = 241 ppm). In an
      attempt to reduce the variation, we conducted a prospective experiment
      standardizing collection procedure, laboratory techniques, phase of production,
      and season of year to more accurately determine the nutrient concentrations of
      swine lagoons in Kansas. In Exp. 2, we used 236 lagoon and 35 hoop barn manure
      samples taken in 2000 from Kansas swine operations to determine the impacts of
      production phase and season of the year on nutrient concentration. The different
      operations with swine lagoons were: 1) sow; 2) nursery; 3) wean-to-finish; 4)
      finish; and 5) farrow-to-finish, with a total of 9, 8, 7, 10, and 8 lagoons
      sampled from each phase of production, respectively. The total N and P
      concentrations from lagoons were 1,402 and 204 ppm, respectively, averaged over
      all samples. Concentrations of total N were higher in wean-to-finish and
      finishing lagoons (P < 0.05) compared with sow and farrow-to-finish lagoons.
      Lagoon analyses also revealed that N concentrations decreased (linear, P < 0.05)
      during the summer and fall compared with winter and early spring. The
      concentration of P was greater (P < 0.05) for wean-to-finish compared with farrow
      to-finish lagoons. Phosphorus concentrations for all lagoons increased
      (quadratic, P < 0.05) from February until June, but then declined steady
      throughout the remainder of the year. Average total N and P in hoop barns were
      8,678 and 4,364 ppm, respectively. No seasonal changes in N and P concentrations
      were observed in manure from hoop barns. Season and type of production phase
      affect the nutrient content of Kansas swine lagoons, and producers will benefit
      from obtaining individual analyses from their lagoons when developing nutrient
      management plans rather than utilizing published reference values.

PMID- 12211373
TI  - Genetic parameters and trends for lean growth rate and its comvonents in U.S.
      Yorkshire, Duroc, Hampshire, and Landrace pigs.
AB  - Records on 361,300 Yorkshire, 154,833 Duroc, 99,311 Hampshire, and 71,097
      Landrace pigs collected between 1985 and April of 2000 in herds on the National
      Swine Registry Swine Testing and Genetic Evaluation System were analyzed. Animal
      model and REML procedures were used to estimate random effects of animal genetic,
      common litter, maternal genetic, and the covariances between animal and maternal
      for lean growth rate (LGR), days to 113.5 kg (DAYS), backfat adjusted to 113.5 kg
      (BF), and loin eye area adjusted to 113.5 kg (LEA). Fixed effects of contemporary
      group and sex were also in the statistical model. Based on the single-trait
      model, estimates of heritabilities were 0.44, 0.44, 0.46, and 0.39 for LGR; 0.35,
      0.40, 0.44, and 0.40 for DAYS; 0.48, 0.48, 0.49, and 0.48 for BF; and 0.33, 0.32,
      0.35, and 0.31 for LEA in the Yorkshire, Duroc, Hampshire, and Landrace breeds,
      respectively. Estimates of maternal genetic effects were low and ranged from 0.01
      to 0.05 for all traits across breeds. Estimates of common litter effects ranged
      from 0.07 to 0.16. A bivariate analysis was used to estimate the genetic
      correlations between lean growth traits. Average genetic correlations over four
      breeds were -0.83, -0.37, 0.44, -0.07, 0.08, and -0.37 for LGR with DAYS, BF, and
      LEA, DAYS with BF and LEA, and BF with LEA, respectively. Average genetic trends
      were 2.35 g/yr, -0.40 d/yr, -0.39 mm/yr, and 0.37 cm2/yr for LGR, DAYS, BF, and
      LEA, respectively. Results indicate that selection based on LGR can improve
      leanness and growth rate simultaneously and can be a useful biological selection
      criterion.

PMID- 12211374
TI  - Repeated-measure animal models to estimate genetic components of mature weight,
      hip height, and body condition score.
AB  - Information on mature weight, hip height, and body condition score from Angus
      cows was analyzed to estimate variance components and compare prediction models.
      Observations from repeated measures were analyzed with animal models with or
      without condition score as a covariate and with or without an effect for
      permanent environment. Heritability (repeatability) estimates for mature weight,
      hip height, and condition score from Method R procedures were 0.40 (0.77), 0.62
      (0.81), and 0.11 (0.38), respectively, from animal models containing a permanent
      environmental effect but without a covariate for condition score. Heritability
      estimates from animal models without a permanent environmental effect were
      similar to repeatability estimates from animal models with it, suggesting
      inflated estimates of genetic variance from models not containing a permanent
      environmental effect. Regressing mature weight on condition score reduced both
      additive genetic variance and permanent environmental variance, increasing the
      heritability estimate of mature weight to 0.54 and altering the biological
      interpretation of the trait. The covariate for condition score had little effect
      on hip height. Regressions of mature weight and hip height on condition score
      were 25.9 kg/unit of body condition score and 0.4 cm/unit, respectively. Least
      squares means for mature weight and hip height tended to increase until 7 and 5
      yr of age, respectively. Condition score tended to increase until 6 yr of age and
      decrease after 8 yr of age. Correlations between breeding value solutions for the
      same trait were high whether or not prediction models included a permanent
      environmental effect or a covariate for condition score, and whether or not the
      variance components used were derived from models containing a covariate for
      condition score. Results suggest the importance of including a permanent
      environmental effect in genetic prediction models for these traits. Whether
      mature weight should be adjusted for body condition is arguable, depending on
      availability of condition score predictions and tools for analyzing mature weight
      and condition score predictions in an environment-specific context.

PMID- 12211375
TI  - Effect of duration of performance test on variance component estimates for lamb
      growth rate.
AB  - The objective was to determine the effect of periods of adjustment and duration
      of performance test on estimating genetic variance parameters for ADG. Variance
      components were estimated from ADG data collected from 1978 to 1984 on a total of
      1,047 Targhee ewe and ram lambs at the U.S. Sheep Experiment Station (Dubois,
      ID). Across all years, lambs averaged 84 +/- 9 d of age and 25 +/- 5.4 kg of
      weight when placed on test. Lambs were provided ad libitum access to a commercial
      pellet of barley grain and ground alfalfa for 14 wk. Every 2 wk, ADG was
      recorded. Overall mean ADG for the entire 14-wk period across all years was 249.3
      +/- 56.5 g. Variance components were estimated from a single-trait animal model
      using REML for cumulative combinations of time on feed in 2-wk intervals from 4
      to 14 wk and varying the adjustment period from 2 to 6 wk. The model included
      fixed effects for year (1978 to 1984), sex of lamb (ewe or ram), and genetic line
      (selected or control), and two covariates (age and weight at beginning of
      performance test). As the duration of the performance test increased, phenotypic
      variances for ADG decreased: 54 and 13 g2 at 4 and 14 wk on test, respectively.
      Also, estimates of direct heritability increased with extended duration on test:
      0.20 +/- 0.06 and 0.35 +/- 0.07 at 4 and 14 wk on test, respectively.
      Heritability estimates increased little after 8 wk on feed (0.33, 0.33,0.38, and
      0.35 for 8, 10, 12, and 14 wk, respectively). Genetic and environmental
      correlations among durations of the performance test were estimated from two
      trait models. All genetic correlations among durations of performance test were
      greater than 0.88 which suggests that all measures of ADG were genetically
      similar. However, environmental correlations among duration of performance test
      ranged from 0.31 to 1.00 with the smaller environmental correlations occurring
      between 4 to 6 wk with 12 to 14 wk on feed. These results indicate that a period
      of 8 wk or greater was sufficient to observe differences among animals for ADG
      due to direct genetic effects under this environment.

PMID- 12211376
TI  - Reflection on the history, coordination, and funding trends for U.S. public meat
      research: information to enhance resource allocation.
AB  - A study was conducted to analyze resource allocation for public meat research in
      the United States and characterize the portfolio of meat research investments.
      Trends in the amount of public resources provided for meat research (beef, pork,
      lamb, and poultry) were analyzed for fiscal years 1980, 1985, 1990, 1995, and
      1997. An in-depth analysis was conducted for data from fiscal year 1998 to
      characterize the profile of the research portfolio. Funding levels and scientist
      year equivalents were aggregated to represent the measures of resource allocation
      for three mutually exclusive research categories: 1) meat quality, 2) food
      safety, and 3) product development and processing. Data for the 1998 profile
      analysis were derived from a computer search based on the combination of key
      words and research classification codes to avoid duplication and cluster research
      projects. Individual research projects were individually reviewed and a
      percentage was assigned to four mutually exclusive research categories: 1) meat
      quality, 2) food safety, 3) product development and processing, and 4) marketing.
      As meat research evolved over the past century, considerable efforts were
      expended by researchers and administrators to ensure the coordination of research
      and program relevance. This is demonstrated by the establishment of numerous
      multistate research committees. Total funding for meat science increased only
      modestly when adjusted for inflation during the two decades of this study;
      however, notable changes occurred in the distribution of resources in the
      portfolio. Funding for meat quality and product development and processing
      remained virtually unchanged when adjusted for inflation, whereas funding for
      food safety increased considerably. The total number of scientists conducting
      meat research remained virtually unchanged during the period, but the proportion
      allocated to food safety research increased substantially. The federal portion of
      total funding decreased from 61.3% to 51.6% between 1980 and 1997, whereas the
      percentage from both state appropriations and private sources increased.
      Modifications in research emphasis were influenced by industry problems such as
      meat quality, public perceptions about food safety, the availability of research
      funding, scientific advances occurring in molecular biology and genetic
      manipulation, and the changing meat industry. The information in this paper
      provides administrators and researchers the opportunity to make better informed
      decisions about resource allocation for meat research.

PMID- 12211377
TI  - Can goats learn about foods through conditioned food aversions and preferences
      when multiple food options are simultaneously available?
AB  - The objective of this study was to determine the extent to which herbivores are
      able to use conditioned food aversions and preferences to learn about the
      nutritional and toxic properties of food plants, when food options are
      simultaneously available. Conditioned food aversions and preferences have been
      invoked as important mechanisms by which free-ranging herbivores optimize food
      selection by learning about the negative and positive consequences of consuming
      particular plant species through a series of encounters. In most previous tests
      of this hypothesis, access to individual test foods has been separated in time,
      giving animals the opportunity to associate particular foods with particular post
      ingestive effects. We presented animals with a more complex scenario by offering
      test feeds simultaneously during the learning phase. Such a test is an important
      step in assessing the importance of conditioned food responses as mechanisms by
      which herbivores learn to select an optimal diet. We first assessed the ability
      of goats to learn about test foods and their post-ingestive effects, when
      different conifer species were offered on separate days during the learning phase
      and animals were dosed with compounds eliciting positive, negative, or neutral
      post-ingestive effects. We then investigated the ability of animals to learn to
      make appropriate choices when all potential test foods were simultaneously
      available during the learning phase. The results confirmed that goats can learn
      to associate particular foods with particular post-ingestive effects and adjust
      their diet selection accordingly. The success with which animals made such
      associations was greatly reduced when they were presented with test foods
      simultaneously during the learning phase. When test foods were simultaneously
      available, animals tended to select a mixed diet, thereby reducing their
      opportunity to learn about the post-ingestive effects of particular foods. The
      results suggest that caution is required in extrapolating results of artificial
      conditioning experiments to free-ranging herbivores. The results also suggest
      that reducing the risk of toxicity through selection of mixed diets is an
      important component of a successful foraging strategy.

PMID- 12211378
TI  - Influence of macronutrients and activated charcoal on intake of sagebrush by
      sheep and goats.
AB  - We determined if supplemental macronutrients or activated charcoal influenced
      intake of sagebrush, a shrub that contains terpenes. Sheep (lambs 3 mo age, 33
      kg) and goats (kids 5 mo age, 28 kg) were fed supplements high in energy, high in
      protein, or offered a choice between the two supplements before and after
      receiving sagebrush for 4 h/d. The effect of activated charcoal, a compound that
      reduces bioavailability of toxins, was assessed by offering charcoal mixed with a
      carrier or the carrier alone while animals consumed sagebrush for 4 h/d. The
      effects of supplemental macronutirents were tested before and after charcoal
      supplementation. Activated charcoal did not increase intake of sagebrush by sheep
      or goats (P > 0.05), but supplemental macronutrients influenced intake of
      sagebrush by both species (P < 0.05). Intake of sage-brush was markedly higher
      for animals fed the high-protein supplement than for animals fed the high-energy
      supplement (P < 0.05). Lambs (before and after charcoal supplementation) and kids
      (after charcoal supplementation) offered a choice between the two supplements
      used sagebrush at levels comparable to animals supplemented with protein. They
      consumed more CP than animals fed the high-energy supplement and more ME than
      lambs fed the high-protein supplement (P < 0.05). Thus, providing a choice
      between supplements enhanced intake of sagebrush and enabled animals to achieve a
      more balanced intake of macronutrients. Preference for supplement and sagebrush
      also depended on an animal's immediate past history with a supplement. Sheep and
      goats previously fed the high-energy or the high-protein supplement preferred,
      respectively, the high-protein or the high-energy supplement when given a choice
      (P < 0.05). The changes in preference for supplement caused a decreased intake of
      sagebrush by groups that preferred the energy concentrate, and an increased
      intake of sagebrush by groups that preferred the protein concentrate. Thus,
      supplements of different energy and protein densities consistently altered intake
      of sagebrush by sheep and goats.

PMID- 12211379
TI  - Conjugated linoleic acid depresses the delta9 desaturase index and stearoyl
      coenzyme A desaturase enzyme activity in porcine subcutaneous adipose tissue.
AB  - Conjugated linoleic acid (CLA) has been shown to have an effect on subcutaneous
      fatty acid composition and has been reported to decrease stearoyl coenzyme A
      desaturase (SCD) activity by decreasing mRNA expression and(or) catalytic
      activity in rodents and rodent cell lines. This investigation was designed to
      study the effects of CLA, corn oil, or beef tallow supplementation on s.c.
      adipose tissue fatty acid composition, adiposity, SCD enzyme activity, and the
      delta9 desaturase index in piglets. Eighteen crossbred barrows 16 to 18 d of age
      were adapted to diet for 1 wk and then assigned randomly to one of three
      treatments: 1.5% added CLA, 1.5% added corn oil, or 1.5% added beef tallow.
      Barrows were penned individually and fed the supplemental oils for 35 d (to 25.6
      +/- 0.6 kg BW). Subcutaneous adipose tissue samples were obtained after
      slaughter. Fatty acid composition of the s.c. adipose tissue differed for each
      fatty acid measured due to diet with the exception of 18:3. The concentrations of
      CLA trans-10, cis-12 and cis-9, trans-11 were elevated from nondetectable to 1.62
      and 2.52 g/100 g lipid, respectively (P < 0.001 for both isomers). Conjugated
      linoleic acid decreased the delta9 desaturase index (P < 0.01) and SCD enzyme
      activity, expressed as nanomoles of palmitate converted to palmitoleate/(7 min x
      g of tissue) (P = 0.075) and nanomoles of palmitate converted to palmitoleate/(7
      min 105 cells) (P= 0.056). Tallow-fed pigs had a greater proportion of large
      adipocytes (> 700 pL) and the greatest SCD activity. These data provide the first
      direct evidence that dietary CLA depresses SCD enzyme activity in porcine adipose
      tissue, which may in part be responsible for the depression of adiposity by CLA
      observed by others in market weight pigs.

PMID- 12211381
TI  - Technical note: the effect of freezing on Warner-Bratzler shear force values of
      beef longissimus steaks across several postmortem aging periods.
AB  - The objective of this study was to compare fresh and frozen protocol procedures
      for Warner-Bratzler shear force (WBSF) determination on steaks aged for different
      periods of time. The fresh protocol consisted of measuring WBSF on steaks cooked
      on the exact day the aging period ended. The frozen protocol consisted of
      measuring WBSF on steaks that were aged, frozen (-16 degrees C) for approximately
      2 mo, thawed for 24 h, and then cooked. Twenty-two strip loin steaks from each of
      20 crossbred heifers and steers were individually vacuum-packaged and assigned to
      either the fresh or frozen protocol and one of 11 aging periods (1, 2, 3, 4, 5,
      6, 7, 10, 14, 21, or 35 d). The frozen protocol resulted in lower (P < 0.05) WBSF
      values than the fresh protocol for beef longissimus steaks that were aged for 1,
      2, 3, 4, 6, 7, 10, 14, or 35 d postmortem. An interaction (P < 0.05) between
      protocol and postmortem aging resulted from larger differences between protocols
      at shorter aging periods than at longer aging periods. Correlations and mean
      differences revealed that frozen protocol WBSF values were not highly indicative
      of fresh protocol WBSF values at the same period of postmortem aging, but rather
      suggested that frozen protocol WBSF values at shorter aging times were useful in
      estimating WBSF values from fresh protocols at longer aging times. Cooking loss
      was higher (P < 0.05) for frozen vs fresh protocol steaks at all aging periods
      except for 14, 21, or 35 d. These findings suggest that if research constraints
      warrant the freezing of samples, shorter aging periods before freezing (6 and 7
      d) should be used to estimate WBSF of fresh aged beef (14 to 21 d). In trials in
      which several postmortem aging periods or very short aging periods are of
      interest, we recommend that WBSF be assessed using the fresh protocol.

PMID- 12211380
TI  - Short-term feeding of vitamin D3 improves color but does not change tenderness of
      pork-loin chops.
AB  - The objective of this study was to determine the effect of short-term feeding of
      vitamin D3 (D3) on blood plasma calcium concentrations and meat quality of pork
      loin chops. Three experiments were carried out to meet this objective. Experiment
      1 used 250,000 IU and 500,000 IU/d to determine the effective dose of dietary D3
      to raise blood plasma calcium concentration. Experiment 2 used 500,000 IU D3/d to
      determine the appropriate length of feeding time to elevate blood plasma calcium
      prior to harvest. Experiment 3 used 500,000 IU D3/d to determine the
      effectiveness of increased blood plasma calcium in improving postmortem quality
      and tenderness of pork-loin chops. Pigs fed 500,000 IU D3/d in Exp. 1 exhibited
      higher (P < 0.05) and more stable plasma calcium concentration over a 14-d
      feeding trial compared with pigs fed 250,000 IU D3/d and control pigs. Therefore,
      500,000 IU D3/d was the dose chosen for Exp. 2, in which pigs fed 500,000 IU D3/d
      for 3 d prior to harvest exhibited elevated and stable plasma calcium
      concentrations; this length of time was deemed sufficient in which to observe
      differences in postmortem meat tenderness in Exp. 3. Vitamin D3 supplementation
      resulted in lower (P < 0.02) L* values and higher (P < 0.03) a* values of loin
      chops at 7 and 14 d of shelf storage. Vitamin D3 supplementation did not affect
      quality characteristics (measured by use of subjective scores) or tenderness
      (quantified via Warner-Bratzler shear force or Star probe values). On the basis
      of these findings, feeding 500,000 IU D3/d to finishing pigs improved most Hunter
      color values at 14 d of storage but did not improve pork-loin chop tenderness at
      1 to 21 d of retail shelf storage.

PMID- 12211382
TI  - Influence of brahman-derivative breeds and Angus on carcass traits, physical
      composition, and palatability.
AB  - Steers were generated from Angus (A), Beefmaster (BM), Brangus (BA), Gelbray
      (GB), and Simbrah (SB) sires mated to cows of their breed and to Brahman x
      Hereford F1 cows (except A) to characterize their carcass traits, composition,
      and palatability. The 290 steers (48 A, 48 BM, 36 BA, 31 GB, and 46 SB) were
      slaughtered at an equal fatness end point as determined by real-time ultrasound
      and visual evaluation. Angus steers had lighter (P < 0.01), more youthful (P <
      0.01) carcasses with a higher (P < 0.05) quality grade, more (P < 0.01) fat
      thickness, and a larger (P < 0.01) longissimus area/100 kg than BM-, BA-, GB-,
      and SB-sired steers. Angus steers also had a lower (P < 0.01) specific gravity, a
      higher (P < 0.01) percentage fat and less (P < 0.05) lean in the 9th to 11th rib,
      and steaks aged for 10 d were more tender (P < 0.01) than steaks from Brahman
      derivative sired steers. The BM- and BA-sired steers had lighter (P < 0.01), more
      youthful (P < 0.05) carcasses, and smaller (P < 0.01) longissimus area than GB-
      and SB-sired steers. The 9th to 11th rib section from the BM- and BA-sired steers
      had less lean and more bone (P < 0.01) than GB- and SB-sired steers. The BA-sired
      steers had more (P < 0.01) marbling and a higher (P < 0.05) quality grade than BM
      sired steers. The SB-sired steers had heavier (P < 0.01) carcasses than the GB
      sired steers. There were no differences in shear force for steaks aged for 3 d
      for any of the breed types, but with 10 d of aging, steaks from Angus steers were
      more tender, possibly indicating that steaks of Brahman-derivative breeds aged at
      a slower rate than those from Angus.

PMID- 12211383
TI  - Effect of folic acid and glycine supplementation on embryo development and folate
      metabolism during early pregnancy in pigs.
AB  - The present work aimed to determine if different levels of prolificacy either by
      parity or by genetic origin are linked to folate metabolism. Nulliparous
      Yorkshire-Landrace (YL) and multiparous YL, and multiparous Meishan-Landrace (ML)
      sows were randomly assigned to two treatments: 0 ppm or 15 ppm folic acid+0.6%
      glycine. Supplements were given from the estrus before mating until slaughter on
      d 25 of gestation. At slaughter, embryo and endometrial tissues were collected to
      determine concentrations of DNA, protein, and homocysteine. Allantoic fluid
      samples were also collected to determine concentrations of folates, vitamin B12
      and amino acids. Blood samples were taken at first estrus, at mating, and on d 8,
      16, and 25 of gestation to determine serum concentrations of folates, vitamin
      B12, and relative total folate binding capacity (TFBC). Over the entire
      experiment, multiparous YL sows had higher average serum concentrations of
      folates than nulliparous YL sows (P < 0.05) but had similar serum concentrations
      of relative TFBC. Concentrations of folates and relative TFBC averaged higher in
      ML measured over the entire experiment than in multiparous YL sows (P < 0.05).
      Concentrations of serum vitamin B12 were higher in multiparous YL than in ML sows
      or YL nulliparous sows (P < 0.05) over the entire experiment. In allantoic fluid,
      folates, vitamin B12, and essential amino acids contents were significantly lower
      in ML than in YL multiparous sows (P < 0.05). The folic acid+glycine supplement
      increased concentrations of serum folates, but the increase was more marked in
      nulliparous YL sows (nulliparous x folic acid+glycine, P < 0.05). The folic
      acid+glycine supplement had no effect on litter size and embryo survival, but it
      tended to increase embryo DNA in multiparous YL sows (P = 0.06) but not in ML and
      nulliparous YL sows. Homocysteine was decreased by folic acid+glycine supplement
      in embryos from all sows, but in endometrium, the folic acid+glycine effect was
      dependent on parity (nulliparous x folic acid+glycine, P < 0.05). The effects of
      folic acid+glycine on litter size and embryo development and survival and some
      aspects of folate metabolism suggest that the basal dietary content of folic
      acid+glycine was adequate for ML and nulliparous YL sows but not to optimize
      embryo development in YL multiparous sows.

PMID- 12211384
TI  - Dietary lysine and threonine requirements of the pregnant sow estimated by
      nitrogen balance.
AB  - Two experiments were conducted to determine the lysine and threonine requirements
      of gestating sows. In the first experiment, four levels of lysine
      (0.34,0.42,0.48, and 0.56% crude lysine, and 0.24,0.31, 0.38, and 0.45%
      standardized ileal digestible lysine) were compared in eight multiparous Large
      White sows. Each sow received successively the four diets according to a Latin
      square experimental design. Nitrogen balance was measured over 11 d after a 10-d
      period of adaptation to the experimental diet. In the second experiment, four
      threonine/lysine ratios (0.63, 0.73, 0.80, and 0.89 on a crude basis and 0.61,
      0.71, 0.77, and 0.87 on a standardized ileal digestible amino acid basis) were
      compared in 16 multiparous sows, according to a Latin-square experimental design.
      The standardized ileal digestibility of amino acids in the experimental diets was
      determined with ileo-rectal anastomized growing pigs. In the first experiment,
      nitrogen retention was affected by lysine supply (linear, P < 0.001; quadratic, P
      < 0.04). Nitrogen retention was lowest for treatment 1 (8.0 g/ d) and highest for
      treatments 3 and 4 that did not differ. Nitrogen retention plateaued at 14.7 g/d
      in sows consuming 10.5 g/d of digestible lysine. The maintenance requirement for
      digestible lysine was calculated to be 27 mg/kg BW(0.75) with an efficiency of
      utilization of digestible lysine above maintenance at 59%. In the second
      experiment, nitrogen retention was affected (P < 0.03) by the threonine:lysine
      ratio. It was lower for the lowest threonine:lysine ratio (0.63) than for the
      other three treatments that did not differ among each other. These results
      indicate that the optimal standardized digestible threonine:lysine ratio appears
      to be about 0.71 for multiparous gestating sows.

PMID- 12211385
TI  - Alterations in lipid metabolism induced by recombinant bovine tumor necrosis
      factor-alpha administration to dairy heifers.
AB  - Endotoxin induces marked changes in lipid metabolism via its effects on
      cytokines. To evaluate the role of tumor necrosis factor-alpha (TNF) in mediating
      changes of lipid metabolism in ruminants, we performed a crossover saline
      controlled study in Holstein heifers (n = 8; 394.0 kg average BW), investigating
      the metabolic effects of a single intravenous administration of recombinant
      bovine TNF (rbTNF, 5.0 microg/kg). Blood samples were taken from a jugular vein
      at 0 (1100, just before injection), 0.5, 6, 12, and 24 h after each treatment.
      Dry matter intake in the heifers was not affected by single administration of the
      rbTNF. The rbTNF produced early as well as later hypertriglyceridemia (P < 0.05)
      in dairy heifers. The rbTNF also induced an early and sustained rise (P < 0.05)
      in the plasma NEFA concentration. Plasma retinol concentration was decreased (P <
      0.05) at 24 h after rbTNF injection, whereas the a-tocopherol concentration was
      not significantly affected by rbTNF treatment. At 0.5 and 24 h, there was an
      increase (P < 0.05) in the plasma concentration of the very-low-density
      lipoprotein (VLDL) fraction in rbTNF-treated heifers. Between 6 and 24 h after
      rbTNF treatment, concentration of the low-density lipoprotein fraction declined
      (P < 0.05) but the high-density lipoprotein fraction was not altered in the rbTNF
      treated heifers. These results indicate that TNF produces a hypertriglyceridemic
      response associated with an increase of the VLDL fraction and a disturbance of
      retinol metabolism in dairy heifers.

PMID- 12211386
TI  - Serum leptin and its adipose gene expression during pubertal development, the
      estrous cycle, and different seasons in cattle.
AB  - Circulating concentrations of leptin and IGF-I, leptin gene expression, and serum
      binding of [126I]ovine leptin in cattle during pubertal development, as well as
      leptin gene expression and circulating concentrations of leptin during the
      estrous cycle and different calendar seasons, were investigated. Multivariate
      regression analysis was utilized to evaluate temporal changes in BW, leptin mRNA,
      and serum concentrations of IGF-I and leptin normalized to the week of puberty
      (Exp. 1). Body weight accounted for most of the variation associated with the
      onset of puberty in the full regression model (R2 = 0.99; P < 0.01). However,
      serum leptin was closely related to changes in BW (r = 0.85; P < 0.02) and in the
      absence of BW was most predictive of pubertal onset (r2 = 0.73; P < 0.01). Mean
      concentrations of leptin increased (P < 0.0001) linearly from 16 wk before until
      the wk of pubertal ovulation in yearling heifers reaching sexual maturation from
      early spring to midsummer. Leptin mRNA transformed to a percent of the value at
      puberty increased (P < 0.02) as puberty approached, but serum leptin and leptin
      mRNA values were not well correlated. We found no evidence of leptin-binding
      proteins in serum of developing heifers. Combined mean serum concentrations of
      IGF-I (ng/mL) during periods III and IV (-9 wk to wk of puberty; 216.6 +/- 9)
      were 21% higher (P < 0.0001) than combined mean concentrations of IGF-I during
      periods I and II (-19 to wk of puberty; 193 +/- 10). In mature heifers and cows
      (Exp. 2), serum leptin tended to decrease (P = 0.10) during the late luteal/early
      follicular phase of the estrous cycle, which corresponded to a reduction (P <
      0.03) in adipocyte leptin gene expression. In mature ovariectomized cows, serum
      concentrations of leptin increased (P < 0.001) by 34% from early winter to the
      summer solstice and remained unchanged throughout the remainder of the year (Exp.
      3). Results from these studies indicate that marked increases in both circulating
      leptin and leptin gene expression occur in developing heifers during pubertal
      development and are associated with increases in serum IGF-I and BW. Seasonal
      effects on circulating leptin observed in mature cows from winter to summer could
      also plausibly account for a portion of the prepubertal rise in serum leptin
      observed in heifers.

PMID- 12211388
TI  - Supplementing barley or rapeseed meal to dairy cows fed grass-red clover silage:
      I. Rumen degradability and microbial flow.
AB  - The present study was conducted to measure the flow of microbial and nonmicrobial
      N fractions entering the omasal canal of lactating dairy cows fed grass-red
      clover silage supplemented with barley and rapeseed meal. Four ruminally
      cannulated Finnish Ayrshire dairy cows were fed, in a 4 x 4 Latin square design,
      grass-red clover silage alone or supplemented with (on DM basis) 5.1 kg/d of
      barley, 1.9 kg/d of rape-seed meal or 5.1 kg/d of barley and 1.9 kg/d rapeseed
      meal. Nonammonia N flow entering the omasal canal was fractionated into microbial
      and nonmicrobial N using 15N. Microbial N was fractionated into N associated with
      liquid-associated bacteria, particle-associated bacteria, and protozoa.
      Supplementation of diets with barley increased microbial N flow entering the
      omasal canal (P < 0.01) but had no effect on nonmicrobial N flow. Increased
      microbial N flow was attributed to liquid-associated bacteria and protozoa.
      Barley had no effect on apparent ruminal N degradability, but increased true
      ruminal N degradability (P < 0.01). Barley had no effect on urinary N excretion,
      but increased daily N retention (P = 0.03). Furthermore, barley supplementation
      decreased ruminal (P = 0.02) and total tract (P < 0.01) NDF digestibility.
      Supplementation of diets with rapeseed meal increased apparent ruminal N
      degradability (P < 0.01) and nonmicrobial N flow entering the omasal canal (P <
      0.01), but had no effect on true ruminal N degradability. Despite higher N
      excretion in urine, rapeseed meal improved daily N retention (P < 0.01). Milk
      yield was increased (P < 0.01) by barley and rapeseed meal supplements, with the
      responses being additive. Responses attained with barley were primarily due to
      increased energy supply for ruminal microbes and improvements in energy and
      protein supply for the animal. However, provision of readily digestible
      carbohydrates in barley did not improve microbial capture of ruminal ammonia.
      Benefits associated with rapeseed meal supplementation were explained as an
      increase in the supply of ruminally undegradable protein.

PMID- 12211387
TI  - Metabolism of propionate and 1,2-propanediol absorbed from the washed
      reticulorumen of lactating cows.
AB  - To investigate the metabolism of 1,2-propanediol (PPD) in lactating cows
      independently of normal rumen microbial metabolism, three ruminally cannulated
      lactating Holstein cows were subjected to three experimental infusion protocols
      under washed reticulo-ruminal conditions in a Latin square design. Reticulo
      ruminal absorption rates were maintained for 420 min by continuous intraruminal
      infusion of VFA and PPD. With the control treatment, 1,246 +/- 39 mmol/ h of
      acetate and 213 +/- 5 mmol/h of butyrate were absorbed from the reticulorumen.
      With the propionate treatment, 1,148 +/- 39 mmo/h of acetate, 730 +/- 23 mmol/h
      of propionate and 196 +/- 5 mmol/h of butyrate were absorbed from the
      reticulorumen. With PPD treatment, 1,264 +/- 39 mmol/h of acetate, 220 +/- 5
      mmol/h of butyrate and 721 +/- 17 mmol/h of PPD were absorbed from the
      reticulorumen. Glucose irreversible loss rate (ILR), as well as the relative
      enrichment of plasma lactate and alanine, were determined by primed continuous
      infusion of [U-13C]glucose in a jugular vein. Treatments did not affect (P >
      0.10) the plasma concentrations of glucose (4.2 +/- 0.1 mmoVL), alanine (0.14 +/-
      0.01 mmol/L), or insulin (80 +/- 25 pmol/L). The plasma concentration of lactate
      was higher (P < 0.05) with both propionate (0.84 +/- 5 mmol/L) and PPD treatment
      (0.81 +/- 5 mmol/ L) compared with the control treatment (0.29 +/- 0.5 mmol/L).
      The plasma concentration of pyruvate was higher (P < 0.05) with the propionate
      treatment (0.09 +/- 0.01 mmol/L) compared with the control treatment (0.03 +/-
      0.01 mmol/L). The plasma concentration of 3-hydroxybutyrate was lower (P < 0.05)
      with the propionate treatment (0.15 +/- 0.03 mmol/L) compared with the control
      treatment (0.40 +/- 0.03). With the PPD treatment, the plasma concentrations of
      pyruvate and 3-hydroxybutyrate were in between the other treatments and tended (P
      < 0.10) to be different from both. The plasma concentration of PPD increased
      throughout the infusion period with the PPD treatment and reached a concentration
      of 4.9 +/- 0.6 mmol/L at 420 min. The ILR of glucose was not affected (P > 0.10)
      by treatments (441 +/- 35 mmol/h). The relative 13C enrichment of plasma lactate
      compared with that of glucose decreased (P < 0.05) with the PPD treatment
      compared with the control treatment (44 to 21 +/- 3%). It was concluded that PPD
      has a low rate of metabolism in cows without a normal functioning rumen, although
      about 10% of the absorbed PPD was metabolized into lactate.

PMID- 12211389
TI  - Supplementing barley or rapeseed meal to dairy cows fed grass-red clover silage:
      II. Amino acid profile of microbial fractions.
AB  - Four ruminally cannulated dairy cows were used to examine the effect of diet on
      the AA composition of rumen bacteria and protozoa, and the flow of microbial and
      nonmicrobial AA entering the omasal canal. Cows were offered grass-red clover
      silage alone, or that supplemented with 5.1 kg DM of barley, 1.9 kg DM of
      rapeseed meal, or 5.1 kg DM of barley and 1.9 kg DM of rapeseed meal according to
      a 4 x 4 Latin square design with a 2 x 2 factorial arrangement of treatments.
      During the first 10 d of each period, cows had free access to silage and,
      thereafter intake was restricted to 95% of ad libitum intake. Postruminal digesta
      flow was assessed using the omasal canal sampling technique in combination with a
      triple marker method. Liquid- (LAB) and particle- (PAB) associated bacteria were
      isolated from digesta in the reticulorumen and protozoa from digesta entering the
      omasal canal. Microbial protein flow was determined using 15N as a microbial
      marker. Flows of AA entering the omasal canal were similar in cows fed silage
      diets supplemented with barley or rapeseed meal. However, rapeseed meal increased
      nonmicrobial AA flow while barley increased the flow of AA associated with LAB
      and protozoa. Diet had negligible effects on the AA profile of microbial
      fractions. Comparison of AA profiles across diets indicated differences between
      LAB and PAB for 10 out of 17 AA measured. Rumen bacteria and protozoa were found
      to be different for 14 out of 15 AA measured. For grass silage-based diets,
      energy and protein supplementations appear to alter postruminal AA supply through
      modifications in the proportionate contribution of microbial and nonmicrobial
      pools to total protein flow rather than as a direct result of changes in the AA
      profile of microbial protein.

PMID- 12211390
TI  - Methionine as a methyl group donor in growing cattle.
AB  - Holstein steers were used in two 5 x 5 Latin square experiments to evaluate the
      sparing of methionine by alternative sources of methyl groups (betaine and
      choline). Steers were housed in metabolism crates and limit-fed a soybean hull
      based diet high in rumen degradable protein. To increase energy supply, ruminal
      infusions of volatile fatty acids and abomasal infusions of glucose were
      provided. An amino acid mixture, limiting in methionine, was infused abomasally
      to ensure that nonsulfur amino acids did not limit protein synthesis. Treatments
      for Exp. 1 were abomasal infusion of 1) water, 2) 2 g/d L-methionine, 3) 1.7 g/d
      L-cysteine, 4) 1.6 g/d betaine, and 5) 1.7 g/d L-cysteine + 1.6 g/d betaine.
      Treatments for Exp. 2 were abomasal infusion of 1) water, 2) 2 g/d L-methionine,
      3) 8 g/d betaine, 4) 16 g/d betaine, and 5) 8 g/d choline. In both experiments,
      nitrogen retention increased in response to methionine (P < 0.05), demonstrating
      a deficiency of sulfur amino acids. Responses to cysteine, betaine, and choline
      were all small and not significant. The lack of response to cysteine indicates
      that the response to methionine was not due to transsulfuration to cysteine or
      that cysteine supply did not alter the flux of methionine through
      transsulfuration. The lack of response to betaine suggests that the steers' needs
      for methyl groups were met by the dietary conditions or that betaine was
      relatively inefficient in increasing the remethylation of homocysteine to
      methionine and, thereby, reducing the synthesis of cysteine from homocysteine.
      Under our experimental conditions, responses to methionine were likely due to a
      correction of a deficiency of methionine per se rather than of methyl group
      donors.

PMID- 12211391
TI  - Observational study of temperature, moisture, pH and bacteria in straw bedding,
      and faecal consistency, cleanliness and mastitis in cows in four dairy herds.
AB  - A study of four dairy farms showed that much of the straw stored for bedding was
      too wet (over 15 per cent moisture content). Most of the beds, including their
      top surfaces, were damp (above 75 per cent relative humidity). The temperature of
      the surface of most of the straw beds was related to the air temperature, many
      being below 15 degrees C, but below the surface the temperatures of most beds
      reached between 15 degrees C and 45 degrees C within about a week of their being
      renewed. Bacterial counts also reached a plateau within one to two weeks. The pH
      of the top layers of straw was usually between 8.5 and 9.5. Adding lime daily to
      the top layer of the straw failed to raise the pH to levels at which Escherichia
      coli and Streptococcus uberis do not survive. Most of the counts of E coli and
      faecal streptococci in the top layers of straw were above 10(6) colony-forming
      units/g. Counts of E coli and S uberis were much higher in the beds of early
      lactation cows than in those of dry cows. Many of the early lactation cows were
      heavily and persistently contaminated with faeces. Dry cows were much cleaner.
      Groups of cows with firmer faeces were also cleaner. The farm with the lowest
      incidence of mastitis had the cleanest cows and the most satisfactory beds.

PMID- 12211392
TI  - Seroprevalence of Actinobacillus pleuropneumoniae serovars 2, 3 and 9 in
      slaughter pigs from Belgian fattening farms.
AB  - Fifty randomly selected fattening pig herds were studied to investigate the
      epidemiological characteristics of infections with Actinobacillus
      pleuropneumoniae serovars 2, 3 and 9, and to identify risk factors for their
      within-herd seroprevalences. Information about 13 farm characteristics was
      obtained by means of a questionnaire and used to assess potential risk factors
      for the percentage of slaughter pigs with antibodies against each of the three
      serovars. The presence of antibodies was measured with an indirect ELISA. The
      median within-herd seroprevalence for serovar 2 was 58 per cent (range 0 to 100
      per cent), for serovar 3, 53 per cent (range 10 to 95 per cent), and for serovar
      9, 35 per cent (range 5 to 100 per cent). All but one farm tested positive for A
      pleuropneumoniae serovar 2, and all the farms were positive for A
      pleuropneumoniae serovars 3 and 9. There was a positive association (P < 0.05)
      between each pair of serovars. The within-herd seroprevalence of serovar 2 was
      significantly associated with the density of pig herds in the municipality (odds
      ratio [OR] = 1.60; P < 0.05) and with the absence of preventive medication at the
      start of the fattening period (OR = 2.77; P < 0.10). No significant risk factors
      were found for serovar 3. The percentage of pigs positive for serovar 9 was
      significantly associated with a slaughter date in June (OR = 2.30; P < 0.10) and
      with herds in which the finishing houses were not divided into separate
      compartments (OR = 2.99; P < 0.05).

PMID- 12211393
TI  - Toxin types of Clostridium perfringens isolated from free-ranging, semi
      domesticated reindeer in Norway.
AB  - Samples of faeces were taken from 166 healthy domesticated reindeer (Rangifer
      tarandus tarandus) from three flocks in different reindeer husbandry districts in
      northern Norway and examined bacteriologically for the presence of Clostridium
      perfringens. The organism was isolated from 98 (59 per cent) of the reindeer. The
      isolates were classified into C perfringens toxin types by PCR analysis specific
      for the genes encoding the four major toxins (alpha, beta, epsilon and tau) and
      were subclassified by the detection of the genes encoding C perfringens beta2
      toxin and enterotoxin. All the isolates belonged to C perfringens toxin type A.
      In addition, 15 of the 98 isolates were PCR-positive for the beta2-toxin gene,
      and two of the isolates had the the gene encoding for enterotoxin.

PMID- 12211394
TI  - Encephalitis of unknown aetiology in young starlings (Sturnus vulgaris) and house
      sparrows (Passer domesticus).

PMID- 12211395
TI  - Embryonic development in quadruplet equine pregnancies.

PMID- 12211396
TI  - Uterus didelphys in a goat.

PMID- 12211397
TI  - Need for vigilance in the aftermath of FMD and CSF.

PMID- 12211398
TI  - Fasciolosis in cattle and sheep.

PMID- 12211399
TI  - Future of the RCVS library.

PMID- 12211400
TI  - RCVS fees for 2003.

PMID- 12211401
TI  - Hunting debate.

PMID- 12211403
TI  - Eliminating HIV-1 reservoirs.
AB  - HIV-1 infection can now be treated effectively in many patients in the developed
      world, using combination antiretroviral therapeutics, called highly active
      antiretroviral therapy (HAART). Nevertheless, these regimens do not cure HIV-1
      infection. Residual disease is maintained via proviral latency in resting CD4+ T
      lymphocytes and possibly monocytes/macrophages. In addition, low-level viral
      replication continues in a cryptic manner during HAART. As such, a variety of
      approaches to both activate the latent reservoirs and deplete residual viral
      replication are being developed. In understanding the molecular pathogenesis of
      HIV-1 disease, one can potentially target these cellular reservoirs of HIV-1
      persistence.

PMID- 12211404
TI  - Immune reconstitution in HIV-1-infected patients.
AB  - HIV-1-specific CD8 cytotoxic and CD4 helper T-lymphocytes, which are respectively
      the central effector and regulatory cells in viral infections, together with
      fully functional antigen-presenting cells, are essential at all stages of HIV-1
      infection to control viral activity. Recent studies indicate that such protective
      HIV-1-specific immune responses can be preserved/induced in HIV-1-infected
      individuals, utilizing strategies such as treatment interruption after early
      HAART. Despite successful combination antiretroviral drug therapy, strong anti
      HIV-1 T-cell responses are often not apparent in chronic HIV-1 infection,
      diminishing the probability of viral eradication. Thus, the therapeutic use of
      immunization and cytokines are required to induce and steer immunity towards a
      desirable outcome. Here, we review and discuss therapeutic immunization and
      immunotherapy with regard to their potential use in the treatment of chronic HIV
      1 infection.

PMID- 12211405
TI  - SJ-3366 Sam Jin Pharmaceutical.
AB  - Sam Jin is investigating SJ-3366, a non-nucleoside reverse transcriptase
      inhibitor (NNRTI), for the potential treatment of HIV infection [302450]. As well
      as acting as an NNRTI, SJ-3366 also interferes with HIV-1 entry via an
      intermediate target formed after virus-cell attachment [341146], [363900]. As of
      June 1998, Sam Jin had been awarded a patent for SJ-3366 in South Africa, with
      applications pending in 22 other countries [302450].

PMID- 12211406
TI  - Recent advances in corticosteroids for the treatment of asthma.
AB  - The currently available therapy for asthma is highly effective and is able to
      control the disease in the majority of patients. There are two types of
      treatments for asthma: rapid relief of symptoms, used as needed and long-term
      control, used on a regular basis. Rapid relief is provided by short-acting beta2
      agonists and anticholinergics. The control of asthma is achieved by treatment
      with inhaled corticosteroids (ICS), theophylline, long acting beta2-agonists and
      antileukotrienes. Beta2-agonists and corticosteroids dominate asthma therapy,
      with over 65% of the market share. Corticosteroids are the most effective drugs
      available to clinicians for the control of inflammation in patients with asthma.
      ICS have revolutionized the treatment of asthma and are now the first-line
      treatment for chronic asthma in all ages.

PMID- 12211407
TI  - Anti-IgE therapy of asthma.
AB  - There is a strong association between serum levels of immunoglobulin E (IgE) and
      asthma development. Allergen binds to IgE on basophils and mast cells, leading to
      cell degranulation and release of inflammatory mediators. A humanized antibody to
      IgE that reduces circulating free IgE, omalizumab (Genentech Inc/Novartis
      AG/Tanox Inc), inhibits the early- and late-phase response to allergen. In
      clinical trials of moderate-to-severe asthma, omalizumab allowed a reduction in
      oral and inhaled corticosteroids while improving peakflows and reducing
      exacerbations, particularly in patients at high risk of serious asthma-related
      morbidity. Omalizumab is a useful addition to the treatment armamentarium for
      patients with moderate-to-severe asthma.

PMID- 12211408
TI  - ONO-6818 Cortech/Ono.
AB  - ONO-6818 (CP-955) is the lead compound in a series of orally bioavailable
      neutrophil elastase inhibitors licensed from Cortech and under investigation by
      Ono for the potential treatment of inflammatory conditions, such as rheumatoid
      arthritis, inflammatory bowel disease and chronic obstructive pulmonary disease
      (COPD) [174095]. ONO-6818 was in phase I studies for COPD in Japan as of December
      1999 [366431]. Phase I trials for this indication in Japan and the US were
      ongoing in September 2001 [368565], [422782], [446138]. As of June 2002, however,
      a number of unconfirmed reports stated that the compound had moved into phase II
      trials in Japan and was in preparation for phase II trials in the US [456596],
      [456597].

PMID- 12211409
TI  - Roflumilast Altana Pharma.
AB  - Roflumilast is a specific PDE4 inhibitor being developed by Altana Pharma
      (formerly known as Byk Gulden) for the potential treatment of asthma and chronic
      obstructive pulmonary disease [312928].

PMID- 12211410
TI  - Antithrombotic drugs for the treatment of heparin-induced thrombocytopenia.
AB  - Because patients with heparin-induced thrombocytopenia (HIT) have an extremely
      high frequency of developing thrombosis, treatment options other than heparin are
      essential. Prophylaxis against thrombosis should also be considered. The current
      American College of Chest Physicians guidelines for the treatment of acute
      heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) include the use
      of danaparoid, lepirudin or argatroban, alone or in combination with warfarin.
      For documented clinical thrombosis associated with HIT, patients should be
      treated with a direct thrombin inhibitor at therapeutic activated partial
      thromboplastin time for 7 to 10 days. Warfarin should not be used during the
      acute phase of HIT, unless a thrombin inhibitor is being used simultaneously.
      Conversion to warfarin can be done when the acute phase of HIT has passed. Due to
      the high likelihood of cross-reactivity, the use of low molecular weight heparins
      in patients with HIT is not recommended. For prophylactic treatment of HIT
      patients, despite a lack of other indications for anticoagulation, a direct
      thrombin inhibitor can be initiated with a low level of anticoagulation until the
      thrombocytopenia resolves. This regimen is continued until laboratory evidence is
      provided that the HIT antibody is no longer detectable. HIT patients, in addition
      to needing anticoagulation to treat thrombosis, can require anticoagulation for
      non HIT-related events, such as for the treatment of myocardial infarction,
      unstable angina and long-term anticoagulation for heart valves or atrial
      fibrillation. For these situations, and if immediate anticoagulation is needed,
      the use of a direct thrombin inhibitor with switch-over to warfarin is a useful
      option. However, optimal dosing regimens have not been established in all cases.

PMID- 12211411
TI  - Heparin and low molecular weight heparin in thrombosis and beyond.
AB  - Despite efforts in finding and developing new anticoagulants, unfractionated
      heparin and low molecular weight heparin (LMWH) will continue to play a pivotal
      role in the management of thrombotic disorders. While bleeding and heparin
      induced thrombocytopenia represent major side effects of this drug, it has
      remained the anticoagulant of choicefor the prophylaxis and treatment of arterial
      and venous thrombotic disorders, surgical anticoagulation and interventional
      usage. Understanding the heparin structure led to the development of LMWHs,
      synthetic heparinomimetics, antithrombin and anti-Factor Xa agents.

PMID- 12211412
TI  - Oxygen carriers.
AB  - Three polyhemoglobins, formed by intermolecular cross-linking of hemoglobin
      molecules are in advanced phase III clinical trials and two conjugated
      hemoglobins, formed by cross-linking of hemoglobin molecules with soluble
      polymer, are also undergoing clinical trials. A perflubron-based emulsion is
      undergoing phase III clinical trials and a new recombinant human hemoglobin that
      does not bind to nitric oxide is also being developed. New oxygen carriers with
      antioxidant properties are being developed for conditions with potential for
      ischemia-reperfusion injuries. Third generation oxygen carriers are based on
      microencapsulation of hemoglobin and red blood cell enzymes either in liposomes
      or in biodegradable nanocapsules. This review will briefly discuss lessons learnt
      from the past, give an overview on the current status of selected oxygen carriers
      and discuss research areas in need of further development.

PMID- 12211413
TI  - Vitronectin receptors in vascular disorders.
AB  - Various integrin antagonist candidates, including antibodies, cyclic peptides,
      peptidomimetics and non-peptides, have been clinically evaluated and have been
      shown to successfully modulate certain disease processes. The most advanced
      integrin antagonists in clinical development include intravenous platelet
      alphaIIb/beta3 integrin antagonists, leukocyte alpha4/beta1 integrin antagonists
      and vascular alpha v/beta3 antagonists. This review will focus on the key role of
      the alpha v integrin (alpha v/beta3 and alpha v/beta5) in vascular disorders,
      such as angiogenesis-mediated disorders and vascular restenosis.

PMID- 12211414
TI  - ART-123 Asahi Kasei.
AB  - Asahi Kasei is developing a recombinant thrombomodulin (ART-123), a human protein
      with both thrombin inhibiting and protein C stimulating activities, for the
      potential treatment of thromboembolism and blood clotting disorders, such as
      disseminated intravascular thromboembolism [169907]. By September 2000, it had
      entered phase III trials [383525]. A patent, US-05916874, claiming a method for
      treating liver injury and whose composition comprises a thrombomodulin, was
      published in 1999 by the company.

PMID- 12211415
TI  - Orexins (hypocretins): their role in appetite and arousal.
AB  - Serendipity and hypothesis-driven research both contributed to the discovery and
      characterization of two recently identified neuropeptides thought to be involved
      in the control of appetite and arousal. These two peptides, named hypocretin-1
      and -2, or orexin-A and -B, originated from a common precursor, prepro-hypocretin
      or prepro-orexin, encoded by a gene localized to human chromosome 17q21.
      Orexin/hypocretin neuropetides are produced by a small set of neurons in the
      lateral hypothalamic and perifornical areas, classically involved in the control
      of feeding behavior, blood pressure and central regulation of immune function.
      Orexin-/hypocretin-containing neurons project widely to the CNS, and orexin
      receptors have been found in areas known to participate in the control of
      feeding, sleep, wakefulness, neuroendocrine homeostasis and autonomic regulation.
      Initially, a role in appetite control was suggested as the main action of the two
      hypothalamic neuropetides, as their site of synthesis and incretion, the lateral
      hypothalamus, is primarily involved in the control of food ingestion. Destruction
      of lateral hypothalamic areas results in underfeeding, and orexins were thought
      to be the substances mediating appetite-stimulating drives. Further studies
      indicate a more complex array of functions and effects. The orexin signaling
      pathway is now thought to participate in a complex cycle of energy homeostasis,
      including the control of food intake, waking time, motor activity, metabolic
      rate, heart rate and blood pressure.

PMID- 12211416
TI  - Drugs under investigation for attention-deficit hyperactivity disorder.
AB  - There has been substantial development of pharmacological treatments for
      attention-deficit hyperactivity disorder (ADHD) recently. The greatest change is
      the approval of new delivery systems for methylphenidate (MPH) and amphetamine
      (AMP) that permit once a day dosing. There are also a number of new compounds
      under development for the disorder, including several non-stimulant agents. These
      compounds target the noradrenergic, histaminergic and dopaminergic systems. The
      recent developments in the pharmacological treatment of ADHD should increase
      therapeutic options and the percentage of individuals with the disorder who can
      be effectively treated.

PMID- 12211417
TI  - Risperidone: a potential treatment for autism.
AB  - Autistic disorder (autism) is a neuropsychiatric syndrome characterized by marked
      deficits in reciprocal social relatedness, communication impairment and a narrow
      range of interests and/or repetitive behaviors. Autism is frequently associated
      with, but distinct from, mental retardation. It is classified as a subtype of
      pervasive developmental disorder (PDD) along with 'PDD not otherwise specified'
      (NOS) and Asperger's disorder. These disorders have in common marked impairments
      in social relatedness. Individuals with autism may also have other symptoms that
      become the primary focus of psychiatric treatment. These associated symptoms
      include aggression, self-injury, irritability and anxiety.

PMID- 12211418
TI  - Duloxetine Eli Lilly.
AB  - Duloxetine is a serotonin (5-HT) and norepinephrine (NE) uptake inhibitor in pre
      registration for depression. In vivo studies demonstrate that duloxetine inhibits
      5-HT and NE transporters and this may induce an antidepressant effect [159168].
      In humans, duloxetine has a low affinity for most 5-HT subtypes and for
      muscarinic, histamine H1, alpha1-adrenergic, alpha2-adrenergic and dopamine D2
      receptors [444103]. Thus, it is not surprising that the meta-analysis of four
      recent clinical studies suggests duloxetine is a potent and well-tolerated
      antidepressant [429723]. By December 2001, Lilly had filed an NDA for depression.
      The launch of duloxetine is planned for the second half of 2002 [434250],
      [436220]. In April 2002, filing for stress urinary incontinence was anticipated
      for later in 2002 [456894]. Analysts at Banc of America predicted in April 2002,
      that the drug will be launched in the first quarter of 2003. The company projects
      US $400 million in revenue in 2003 and anticipates duloxetine to reach peak sales
      of over US $1 billion [450920]. Analysts at Morgan Stanley, projected US $25
      million in sales in the fourth quarter 2002, rising to US $900 million in 2006
      [450937]. At the same time, Credit Suisse First Boston anticipated launch for
      late 2002, with US $220 million in duloxetine revenues in 2003 and US $457
      million in 2004 [450936].

PMID- 12211419
TI  - MethyPatch Noven.
AB  - Noven Pharmaceuticals is developing a transdermal patch formulation of
      methylphenidate for the treatment of attention deficit hyperactivity disorder
      (ADHD) [325808]. Phase III trials were completed in February 2002 [438893]; at
      this time, the company predicted a 2003 launch for the product [441478]. In April
      2002, based on pivotal phase III trial results, Noven expected to file an NDA
      with the FDA in mid-2002 and to launch the product in the second half of 2003
      [445181]. In June 2002, the NDA was filed [456552]. The original phase III trials
      were completed in the first quarter of 2001 [407254]. However, preliminary
      analysis of the phase III trial, reported in April 2001, suggested that a
      supplemental study would be required to support the filing [403771]. At this
      time, an NDA filing, originally planned for the second quarter of 2001, was
      rescheduled for the first half of 2002 [400122], [407640], [410285], [441478]. As
      of August 2001, the supplemental study was expected to begin in autumn of that
      year [417877]. In October 2001, enrolment was initiated in Noven's pivotal,
      double-blind, placebo-controlled, multicenter phase III study of MethyPatch
      [427321], and it was completed in February 2002 [438893]. In May 2001, the
      company was issued patent US-06210705 relating to the transdermal delivery of
      methylphenidate for the treatment of ADHD [410285]. In June 2001, ABN AMRO
      predicted sales of US $61 million in 2002, rising to US $74 million in 2005
      [422762]. Analysts at Morgan Stanley predicted in May 2002 that the product would
      make US sales of US $9.1 million in 2003, rising to US $22.5 million in 2006
      [454573].

PMID- 12211420
TI  - Escitalopram H Lundbeck.
AB  - Lundbeck and Forest have developed and launched escitalopram, the therapeutically
      active (S)-enantiomer of citalopram, as an improved follow-up compound for the
      potential treatment of depression. In December 2001, Lundbeck received Swedish
      approval for the treatment of depression and panic disorder [433058], and in
      January 2002, the product was approved in Switzerland for the treatment of
      depression [434736]. By May 2002 it had been approved in Belgium, Denmark, the
      UK, France, Iceland, Luxembourg, Norway and Austria, as a result of the European
      Mutual Recognition Procedure. Independently, regulatory authorities in Lithuania
      had also approved the drug for the treatment of depression. Launch in these
      countries will begin immediately after price and reimbursement negotiations are
      completed [450860]. By June 2002, it had been launched in Switzerland, Sweden and
      the UK [454488]. Based on the approvals in the EU, national applications are
      being submitted in several Central and Eastern European countries, where review
      and the first approvals were expected in the second half of 2002. At this time,
      the approval of escitalopram in Australia and Canada was expected in the second
      half of 2002 and the first half of 2003, respectively [450860]. It became evident
      in May 2002, that Portugal, Greece, Italy, Spain, Finland and Germany did not
      intend to approve escitalopram for marketing within the 90-day timeframe, and, at
      this time, Lundbeck, in accordance with the advice of the reference country,
      Sweden, chose to withdraw the registration applications from these six countries.
      At this time, the company still expected escitalopram to be approved in these
      countries [450860]. In the US, Forest submitted an NDA in March 2001 [402983] and
      in January 2002, Forest received an approvable letter from the FDA for
      escitalopram; at this time, US launch was expected in mid-2002 [437487],
      [444243]. By March 2002, Lundbeck had started to supply escitalopram to Forest
      [442326]. Lundbeck and Morchida entered a Japanese development and marketing
      agreement in May 2002, replacing a collaboration with Mitsui [453377].

PMID- 12211421
TI  - Selegiline transdermal system Somerset.
AB  - Somerset is developing a selegiline transdermal system (STS) for potential use in
      the treatment of depression. It has also been developed for Alzheimer's disease
      (AD), Parkinson's disease and attention-deficit hyperactivity disorder (ADHD)
      [182121], although no development has been reported for AD or ADHD in recent
      years. Somerset claims the transdermal system could be more effective than the
      oral formulation of selegiline already marketed [250573]. In May 2001, Somerset
      filed an NDA with the US FDA for STS for the treatment of depression [410848],
      however, in March 2002, the company received a 'non-approvable' letter from the
      FDA requesting additional efficacy data. At this time, Somerset had scheduled a
      meeting with the FDA to review and clarify their comments [456735]. Selegiline
      will be co-promoted in the US by Watson, under the terms of a previous agreement
      [275389].

PMID- 12211422
TI  - Endothelin receptor antagonists as therapeutic agents for cancer.
AB  - Endothelins (ETs) are 21-amino acid peptides involved in many different
      pathological conditions. ETs, mediated by the ET(A) receptor, are mitogenic for
      many types of cancer cells. ETs seem to both promote and inhibit apoptosis,
      dependent on the cell and tissue types. The anti-apoptotic effect of ETs is
      mediated predominantly by the ET(A) receptor. The ET system also plays a role in
      metastases. Indeed, animal studies and human clinical trials with ET(A) receptor
      antagonists suggest that they may be useful therapeutic agents for treating
      cancer. This paper reviews recent studies on the role of the ET system in
      tumorigenesis and provides an update on the recent development of ET receptor
      antagonists, in clinical studies for cancer.

PMID- 12211423
TI  - Atrasentan Abbott.
AB  - Atrasentan is a selective endothelin ET(A) receptor antagonist under development
      by Abbott for the potential treatment of cancer, particularly prostate cancer,
      for which it is in phase III trials [413197]. In July 2002, phase II trials for
      renal, ovarian, lung, colorectal, breast and brain cancers were being initiated
      [457800]. Atrasentan has been granted Fast Track status, allowing for a rolling
      NDA [414666], [443479]; the company was planning to begin filing for prostate
      cancer in late 2003. Atrasentan has also been in phase I trials for hypertension
      [319405], [326268], but development for this indication had been halted by 2001
      [407049].

PMID- 12211424
TI  - CCI-779 Wyeth.
AB  - Wyeth Research (formerly Wyeth-Ayerst Research) is developing the sirolimus
      (rapamycin) analog CCI-779 as a potential treatment for various cancers [320924].
      By November 2001, phase III trials had been initiated [428972], [429576]. In
      October 2001, Raymond James predicted filing in 2003, with a potential launch in
      2005 [426718]. In March 2002, CCI-779, was designated for fast-track development
      by the FDA for the treatment of renal cell carcinoma after failure of initial
      therapy [442535]; at this time phase III trials for renal cell carcinoma and
      phase II trials for various solid tumors were ongoing [444030]. In March 2002,
      Wyeth revealed that filing was anticipated for 2004/2005 [443491]. In June and
      August 2001, Lehman Brothers predicted sales of US $40 million ($20 million in
      the US) in 2003, rising to US $75 million ($38 million in the US) in 2004
      [418901], [420809]. In October 2001, analysts at Raymond James expected potential
      sales of the product at US $250 million [426718]. In May 2002, a patent (WO
      00240000) was published claiming CCI-779 to be useful for the treatment of
      cancers of various origins, including renal, breast, cervical, uterine, head and
      neck, lung, prostate, pancreatic, ovarian, colon, lymphoma and melanoma.

PMID- 12211425
TI  - Is leptin the link between fat and bone mass?
AB  - Recently, leptin has emerged as a potential candidate responsible for protective
      effects of fat on bone tissue. However, it remains difficult to draw a clear
      picture of leptin effects on bone metabolism because published data are sometimes
      conflicting or apparently contradictory. Beyond differences in models or
      experimental procedures, it is tempting to hypothesize that leptin exerts dual
      effects depending on bone tissue, skeletal maturity, and/or signaling pathway.
      Early in life, leptin could stimulate bone growth and bone size through direct
      angiogenic and osteogenic effects on stromal precursor cells. Later, it may
      decrease bone remodeling in the mature skeleton, when trabecular bone turnover is
      high, by stimulating osteoprotegerin (OPG) expression. Leptin negative effects on
      bone formation effected through central nervous system pathway could
      counterbalance these peripheral and positive effects, the latter being
      predominant when the blood-brain barrier permeability decreases or the serum
      leptin level rises above a certain threshold. Thus, the sex-dependent specificity
      of the relationship between leptin and bone mineral density (BMD) in human
      studies could be, at least in part, caused by serum leptin levels that are two-
      to threefold higher in women than in men, independent of adiposity. Although
      these hypotheses remain highly speculative and require further investigations,
      existing studies consistently support the role of leptin as a link between fat
      and bone.

PMID- 12211426
TI  - Insulin-like growth factor I is required for the anabolic actions of parathyroid
      hormone on mouse bone.
AB  - Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the
      mechanism(s) by which it works remains imperfectly understood. Previous studies
      have indicated that PTH stimulates insulin-like growth factor (IGF) I production,
      but it remains uncertain whether IGF-I mediates some or all of the skeletal
      actions of PTH. To address this question, we examined the skeletal response to
      PTH in IGF-I-deficient (knockout [k/o]) mice. These mice and their normal
      littermates (NLMs) were given daily injections of PTH (80 microg/kg) or vehicle
      for 2 weeks after which their tibias were examined for fat-free weight (FFW),
      bone mineral content, bone structure, and bone formation rate (BFR), and their
      femurs were assessed for mRNA levels of osteoblast differentiation markers. In
      wild-type mice, PTH increased FFW, periosteal BFR, and cortical thickness (C.Th)
      of the proximal tibia while reducing trabecular bone volume (BV); these responses
      were not seen in the k/o mice. The k/o mice had normal mRNA levels of the PTH
      receptor and increased mRNA levels of the IGF-I receptor but markedly reduced
      basal mRNA levels of the osteoblast markers. Surprisingly, these mRNAs in the k/o
      bones increased several-fold more in response to PTH than the mRNAs in the bones
      from their wild-type littermates. These results indicate that IGF-I is required
      for the anabolic actions of PTH on bone formation, but the defect lies distal to
      the initial response of the osteoblast to PTH.

PMID- 12211427
TI  - Insulin-like growth factor I effect on the number of osteoblast progenitors is
      impaired in ovariectomized mice.
AB  - Because insulin-like growth factor (IGF) I is an important regulator of bone
      formation, we proposed the hypothesis that IGF-I could contribute in regulating
      the number of osteoblast progenitors (colony-forming unit fibroblast with ALP
      activity [CFU-F/ALP+]). To test ex vivo and in vivo effects of IGF-I on the
      number of CFU-F/ALP+, bone marrow cells (BMCs) derived from normal mice, growth
      hormone (GH)-deficient lit/lit mice, or ovariectomized (OVX) mice were cultured
      and the CFU-F/ALP+ number was counted. Ex vivo treatment of IGF-I increased the
      CFU-F/ALP+ number in a dose-dependent manner compared with vehicle-treated
      control cultures. The CFU-F/ALP+ number was decreased by 20% (p < 0.01; n = 7-9)
      in GH-deficient lit/lit mice compared with age-matched control mice. Four weeks
      after OVX or sham operation, IGF-I (2 microg/g body wt) or vehicle was
      administered twice on day 1, and 5 days later, BMCs were removed from the femur
      and cultured for 10 days (n = 9-10 per group). IGF-I administration increased the
      CFU-F/ALP+ number by 63% (p < 0.01) and 19% (NS), respectively, in sham-operated
      (sham) and OVX mice compared with the vehicle-treated control group. The serum
      IGF-I level was similar in OVX mice compared with sham mice; this finding is
      different from that found in rats in which OVX increases the serum IGF-I level.
      This study showed that IGF-I is an important regulator of osteoblast-progenitor
      number in the BMCs of mice both ex vivo and in vivo and that the IGF-I response
      to increase the number of osteoblast progenitors was impaired in OVX mice.

PMID- 12211428
TI  - Expression of a 1,25-dihydroxyvitamin D3 membrane-associated rapid-response
      steroid binding protein during human tooth and bone development and
      biomineralization.
AB  - The calciotropic hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has been
      established to control skeletal tissue formation and biomineralization via the
      regulation of gene expression. This action involves the well-characterized
      nuclear 1,25(OH)2D3 receptor. However, it has been recognized that several
      cellular responses to 1,25(OH)2D3 may not to be related to the exclusive nuclear
      receptor. Indeed, this secosteroid is able to generate rapid responses that have
      been proposed to be mediated by interactions of the ligand, which is a putative
      cell membrane-associated rapid-response steroid (MARRS) binding protein for
      1,25(OH)2D3 [1,25D3-MARRS]. The nongenomic pathway of 1,25(OH)2D3 was studied
      here in detail by immunolocalization of the 1,25D3-MARRS during the specific
      context of human prenatal development. Western blotting with proteins extracted
      from 4 week- to 27-week-old embryos was performed, evidencing a 65-kDa molecular
      species recognized by antibody Ab 099 generated against synthetic peptides
      corresponding to the N terminus of the 1,25D3-MARRS from chick intestinal
      basolateral membranes. Based on this biochemical conservation of protein in the
      human species, the temporospatial expression patterns were established in the
      craniofacial skeleton at the same ages. Comparative analysis was performed in
      teeth and bones from early morphogenesis to terminal cell differentiation and
      extracellular biomineralization. The data show the potential implication of
      1,25D3-MARRS in the heterogeneous cell population including ameloblasts,
      odontoblasts, osteoblasts, and osteoclasts. The epithelial-mesenchymal cascade
      related to odontogenesis was coincident with a sequence of up- and down
      regulation of immunoreactive 1,25D3-MARRS. Biomineralization was associated with
      a striking up-regulation in the adjoining secretory cells in all tissues.
      Finally, osteoclasts appeared also to express the 1,25D3-MARRS during these early
      phases of bone modeling. Previously obtained data of the nuclear vitamin D
      receptor (VDR) expression and this study on 1,25D3-MARRS suggest the existence of
      cross-talk between the genomic and nongenomic pathways during human development.

PMID- 12211429
TI  - Long bones from the senescence accelerated mouse SAMP6 have increased size but
      reduced whole-bone strength and resistance to fracture.
AB  - The senescence accelerated mouse strain P6 (SAMP6) has emerged as a useful model
      of senile osteoporosis because it has many features of the disease, including low
      trabecular bone formation and low areal bone density. We further characterized
      the SAMP6 model of senile osteoporosis by comparing morphological, mechanical,
      and densitometric properties of femurs and tibias from SAMP6 mice to those of the
      control strain (SAMR1) at 4 months and 12 months of age. SAMP6 long bones had
      increased periosteal width and endosteal area (p < 0.05), resulting in an average
      increase of 30% in moments of inertia (p < 0.05), but no difference in bone area
      (p > 0.05) compared with control. Despite their increased moments of inertia,
      long bones from SAMP6 mice were relatively weak and brittle. Ultimate bending
      moment was reduced by 25%, and both postyield displacement and energy-to-fracture
      were reduced by 60% compared with SAMR1 controls (p < 0.001). Average cortical
      ash fraction was increased slightly from 0.74 in SAMR1 to 0.76 in SAMP6 bones (p
      < 0.05), indicating that increased mineralization may have contributed to the
      brittleness of SAMP6 bones. The relative differences we observed--increased
      endosteal and periosteal dimensions, reduced bending strength, increased
      brittleness, and increased mineralization--are analogous to changes that occur in
      the aging human skeleton. Moreover, these features were consistently observed in
      young (4-month) and old (12-month) animals. These findings extend the previous
      descriptions of the SAMP6 mouse and identify key mechanical features that further
      validate its relevance as a unique and functionally relevant model of senile
      osteoporosis.

PMID- 12211430
TI  - 1Alpha,25-dihydroxyvitamin D3 promotes vascularization of the chondro-osseous
      junction by stimulating expression of vascular endothelial growth factor and
      matrix metalloproteinase 9.
AB  - Vitamin D deficiency results in defects in endochondral bone development
      characteristic of rickets, which include elongation of the cartilaginous growth
      plates and disorganization of the primary spongiosa. These defects are caused in
      part by impaired cartilage mineralization and vascularization of the chondro
      osseous junction. Blood vessel invasion of mineralized cartilage is an essential
      step in endochondral ossification, providing access for cells that degrade
      cartilage as well as those that form bone. Vascular endothelial growth factor
      (VEGF) was shown to be a key regulator of this process when infusion of a
      dominant negative VEGF receptor effectively blocked vascular invasion and
      endochondral ossification in the growth plates of juvenile mice. Here, we show
      that the active metabolite of vitamin D 1alpha,25-dihydroxyvitamin D3
      [1alpha,25(OH)2D3] directly stimulates transcription of mRNAs encoding VEGF121
      and -165 isoforms in the CFK2 chondrogenic cell line. Enhanced VEGF expression
      also was evident in growth plate chondrocytes and osteoblasts in the tibia of
      juvenile mice treated systemically with 1alpha,25(OH)2D3. This was seen in
      conjunction with enhanced expression of matrix metalloproteinase (MMP) 9, which
      activates VEGF stored in the cartilage matrix, in osteoclastic cells adjacent to
      the chondro-osseous junction. The alterations in VEGF and MMP-9 expression were
      accompanied by enhanced vascular invasion of mineralized cartilage, as assessed
      by CD31 immunoreactivity. These results provide evidence that 1alpha,25(OH)2D3
      signaling stimulates VEGF and MMP-9 gene expression and promotes
      neovascularization of the epiphyseal growth plate in vivo through increased
      availability of active growth factor.

PMID- 12211431
TI  - Low-magnitude mechanical loading becomes osteogenic when rest is inserted between
      each load cycle.
AB  - Strategies to counteract bone loss with exercise have had fairly limited success,
      particularly those regimens subjecting the skeleton to mild activity such as
      walking. In contrast, here we show that it is possible to induce substantial bone
      formation with low-magnitude loading. In two distinct in vivo models of bone
      adaptation, we found that insertion of a 10-s rest interval between each load
      cycle transformed a locomotion-like loading regime that minimally influenced
      osteoblast activity into a potent anabolic stimulus. In the avian ulna model, the
      minimal mean (+SE) periosteal labeled surface (Ps.LS) observed in the intact
      contralateral bones (1.6 +/- 1.5%) was doubled after 3 consecutive days of low
      magnitude loading (3.8 +/- 1.5%; p = 0.03). However, modifying the regimen by
      inserting 10 s of rest between each load cycle significantly enhanced the
      periosteal response (21.9 +/- 4.5%; p = 0.03). In the murine tibia model, 5
      consecutive days of 100 low-magnitude loading cycles did not significantly alter
      mean periosteal bone formation rate (BFR) compared with contralateral bones
      (0.011 +/- 0.005 microm3/microm2 per day vs. 0.021 +/- 0.013 microm3/microm2 per
      day). In contrast, separating each of 10 of the same loading cycles with 10 s of
      rest significantly elevated periosteal BFR (0.167 +/- 0.049 microm3/microm2 per
      day; p = 0.01). Endocortical bone formation parameters were not altered by any
      loading regimen in either model. We conclude that 10 s of rest between each load
      cycle of a low-magnitude loading protocol greatly enhances the osteogenic
      potential of the regimen.

PMID- 12211432
TI  - Mechanical properties of adult vertebral cancellous bone: correlation with
      collagen intermolecular cross-links.
AB  - Although the mechanical strength of cancellous bone is well known to depend on
      its apparent density, little is known about the influence of other structural or
      biochemical parameters. This study specifically investigates the cross-linking of
      the collagen in human vertebral bone samples and its potential influence on their
      mechanical behavior. Multiple cylindrical samples were cored vertically in the
      vertebral bodies of nine subjects (aged 44-88 years). Three spinal levels (T9,
      T12 or L1, and L4) and three sample sites within a vertebral body (anterior,
      posterior, and lateral) were used, for a total of 68 samples. The density was
      measured with peripheral quantitative computed tomography (pQCT) and all
      cylinders were mechanically tested in compression. After mechanical testing, they
      were unmounted and used for biochemical analysis. The amount of collagen (wt/wt
      of bone) and its content in reduced immature cross-links, that is,
      hydroxylysinonorleucine (HLNL, mol/mol of collagen) and
      dihydroxylysinornorleucine (DHLNL), as well as stable mature cross-links, that
      is, hydroxylysyl-pyridinoline (HP), lysyl-pyridinoline (LP), and pyrrole cross
      link were determined for each cylinder. None of the biochemical parameters
      correlated to the density. On multiple linear regression, the prediction of the
      mechanical properties was improved by combining density data with direct collagen
      cross-link assessment. The HP/LP ratio appeared as a significant predictor to the
      strength (r = 0.40; p = 0.001) and stiffness (r = 0.47; p < 0.001) samples with a
      high HP/LP ratio being stronger and stiffer. Additionally, the ultimate strain
      correlated to the HP or LP concentration (r = 0.38 or 0.49; p < 0.01). Different
      subjects had different HP/LP ratios and different HP or LP concentrations in
      their vertebral bone samples, and the location of origin within a subject had no
      influence on the concentration. These observations suggest that the nature of the
      organic matrix in adult vertebral bone is variable and that these variations
      influence its mechanical competence.

PMID- 12211433
TI  - Radius bone strength in bending, compression, and falling and its correlation
      with clinical densitometry at multiple sites.
AB  - This study comprehensively analyzes the ability of site-specific and nonsite
      specific clinical densitometric techniques for predicting mechanical strength of
      the distal radius in different loading configurations. DXA of the distal forearm,
      spine, femur, and total body and peripheral quantitative computed tomography
      (pQCT) measurements of the distal radius (4, 20, and 33%) were obtained in situ
      (with soft tissues) in 129 cadavers, aged 80.16 +/- 9.8 years. Spinal QCT and
      calcaneal quantitative ultrasound (QUS) were performed ex situ in degassed
      specimens. The left radius was tested in three-point bending and axial
      compression, and the right forearm was tested in a fall configuration,
      respectively. Correlation coefficients with radius DXA were r = 0.89, 0.84, and
      0.70 for failure in three-point bending, axial compression, and the fall
      simulation, respectively. The correlation with pQCT (r = 0.75 for multiple
      regression models with the fall) was not significantly higher than for DXA.
      Nonsite-specific measurements and calcaneal QUS displayed significantly (p <
      0.01) lower correlation coefficients, and QUS did only contribute to the
      prediction of axial failure stress but not of failure load. We conclude that a
      combination of pQCT parameters involves only marginal improvement in predicting
      mechanical strength of the distal radius, nonsite-specific measurements are less
      accurate for this purpose, and QUS adds only little independent information to
      site-specific bone mass. Therefore, the noninvasive diagnosis of loss of strength
      at the distal radius should rely on site-specific measurements with DXA or pQCT
      and may be the earliest chance to detect individuals at risk of osteoporotic
      fracture.

PMID- 12211434
TI  - Regional alterations of type I collagen in rat tibia induced by skeletal
      unloading.
AB  - Skeletal unloading induces loss of mineral density in weight-bearing bones that
      leads to inferior bone mechanical strength. This appears to be caused by a
      failure of bone formation; however, its mechanisms still are not well understood.
      The objective of this study was to characterize collagen, the predominant matrix
      protein in bone, in various regions of tibia of rats that were subjected to
      skeletal unloading by 4 weeks tail suspension. Sixteen male Sprague-Dawley rats
      (4 months old) were divided into tail suspension and ambulatory controls (eight
      rats each). After the tail suspension, tibias from each animal were collected and
      divided into five regions and collagen was analyzed. The collagen cross-linking
      and the extent of lysine (Lys) hydroxylation in unloaded bones were significantly
      altered in proximal epiphysis, diaphysis, and, in particular, proximal metaphysis
      but not in distal regions. The pool of immature/nonmineralized collagen measured
      by its extractability with a chaotropic solvent was significantly increased in
      proximal metaphysis. These results suggest that skeletal unloading induced an
      accumulation of post-translationally altered nonmineralized collagen and that
      these changes are bone region specific. These alterations might be caused by
      impaired osteoblastic function/differentiation resulting in a mineralization
      defect.

PMID- 12211435
TI  - The effect of in vivo mechanical loading on estrogen receptor alpha expression in
      rat ulnar osteocytes.
AB  - The presence of estrogen receptor alpha (ER alpha) in osteocytes was identified
      immunocytochemically in transverse sections from 560 to 860 microm distal to the
      midshaft of normal neonatal and adult male and female rat ulnas (n = 3 of each)
      and from adult male rat ulnas that had been exposed to 10 days of in vivo daily
      10-minute periods of cyclic loading producing peak strains of either -3000 (n =
      3) or -4000 microstrain (n = 5). Each animal ambulated normally between loading
      periods, and its contralateral ulna was used as a control. In animals in which
      limbs were subject to normal locomotor loading alone, 14 +/- 1.2% SEM of all
      osteocytes in each bone section were ER alpha positive. There was no influence of
      either gender (p = 0.725) or age (p = 0.577) and no interaction between them (p =
      0.658). In bones in which normal locomotion was supplemented by short periods of
      artificial loading, fewer osteocytes expressed ER alpha (7.5 +/- 0.91% SEM) than
      in contralateral control limbs, which received locomotor loading alone (14 +/-
      1.68% SEM; p = 0.01; median difference, 6.43; 95% CI, 2.60, 10.25). The
      distribution of osteocytes expressing ER alpha was uniform across all sections
      and thus did not reflect local peak strain magnitude. This suggests that
      osteocytes respond to strain as a population, rather than as individual strain
      responsive cells. These data are consistent with the hypothesis that ER alpha is
      involved in bone cells' responses to mechanical strain. High strains appear to
      decrease ER alpha expression. In osteoporotic bone, the high strains assumed to
      accompany postmenopausal bone loss may reduce ER alpha levels and therefore
      impair the capacity for appropriate adaptive remodeling.

PMID- 12211436
TI  - A new method for in vivo analysis of parathyroid hormone-calcium set point in
      mice.
AB  - Although methods for measuring the parathyroid hormone (PTH)-calcium set point in
      vivo in humans and large animals exist, translating such methods to the
      increasingly important mouse model poses considerable challenges. We also found
      that manipulation of dietary calcium does not yield sufficiently high or low
      serum calcium levels to achieve the minimum and maximum PTH levels needed for set
      point estimations. Therefore, we developed a new method for in vivo evaluation of
      the relative set point in mice. Intraperitoneal injection of calcium gluconate
      caused progressive increases in serum calcium over 120 minutes, with
      corresponding decreases in serum PTH levels. Intraperitoneal injection of Na2
      EGTA caused a nadir of serum calcium at 30 minutes and a corresponding peak value
      of serum PTH. The lowest and highest serum calcium concentrations achieved were
      6.7 mg/dl and 10.0 mg/dl, respectively. Linear regression analyses indicated high
      correlation coefficients (serum calcium vs. serum PTH; r = 0.969). To obtain the
      additional data points needed for set point estimation, blood was collected 30
      minutes after intraperitoneal injection by tail nicking from three mice once a
      day, on 8 consecutive days, using multiple doses of calcium gluconate or Na2
      EGTA. The lowest and highest serum calcium concentrations achieved were 5.0 mg/dl
      and 11.4 mg/dl. Maximum and minimum PTH levels were indeed observed, and a
      sigmoidal curve with a set point of 7.8 mg/dl was readily generated by the four
      parameter model that was fit using a nonlinear mixed effects statistical
      approach. This protocol for in vivo set point analysis should be applicable in
      the future study of multiple genetically engineered and pharmacologically treated
      mouse models.

PMID- 12211437
TI  - Long-term predictions of the therapeutic equivalence of daily and less than daily
      alendronate dosing.
AB  - Less than daily alendronate dosing has been identified as an attractive
      alternative to daily dosing for patients and physicians. A recent 2-year study
      found bone mineral density (BMD) changes caused by weekly alendronate dosing
      therapeutically equivalent to that caused by daily dosing. There are no methods
      that can be used to predict how long therapeutic equivalence will be maintained
      after the first 2 years of treatment. In addition, it is unclear if dosing less
      frequently than weekly also might be therapeutically equivalent to daily dosing.
      In this study we use a computer simulation to develop predictions of the
      therapeutic equivalence of daily and less than daily dosing over time periods as
      long as a decade. The computer simulation uses a cell-based computer model of
      bone remodeling and a quantitative description of alendronate
      pharmacokinetics/pharmacodynamics (PK/PD). The analyses suggest that less than
      daily dosing regimens do not increase BMD as much as daily dosing. However, model
      predictions suggest that dosing as frequent as weekly still may be
      therapeutically equivalent to daily dosing over periods as long as 10 years. In
      addition, the simulations predict dosing less frequently than weekly may be
      therapeutically equivalent to daily dosing within the first year of treatment but
      may not be therapeutically equivalent after 10 years. Hypotheses based on these
      simulations may be useful for determining which dosing regimen may be most
      attractive for clinical trials.

PMID- 12211438
TI  - Cyclic adenosine monophosphate/protein kinase A mediates parathyroid
      hormone/parathyroid hormone-related protein receptor regulation of
      osteoclastogenesis and expression of RANKL and osteoprotegerin mRNAs by marrow
      stromal cells.
AB  - Parathyroid hormone (PTH) is a major regulator of osteoclast formation and
      activation, effects that are associated with reciprocal up- and down-regulation
      of RANKL and osteoprotegerin (OPG), respectively. The roles of specific
      downstream signals generated by the activated PTH/PTH-related protein (PTHrP)
      receptor (PTH1R), such as cyclic adenosine monophosphate/protein kinase A
      (cAMP/PKA) and phospholipase C/protein kinase C (PLC/PKC), in controlling RANKL
      and OPG expression and osteoclastogenesis remain uncertain. In MS1 conditionally
      transformed clonal murine marrow stromal cells, which support PTH-induced
      osteoclast formation from cocultured normal spleen cells, PTH(1-34) increased
      RANKL and macrophage colony-stimulating factor (M-CSF) mRNA expression and
      decreased that of OPG when present continuously for 7-20 days at 37 degrees C in
      the presence of dexamethasone (Dex). In cells precultured for 7 days and then
      treated with PTH(1-34), similar reciprocal regulation of RANKL and OPG occurred,
      maximally at 6-24 h, that was of greater amplitude than the changes induced by
      chronic (7-10 days) PTH exposure. These acute effects of PTH(1-34) were mimicked
      by PKA stimulators (8-bromoadenosine [8Br]-cAMP or forskolin [FSK]), blocked by
      the PKA inhibitor Rp-cAMPs but unaffected by the PKC inhibitor GF109203X. Amino
      truncated PTH(1-34) analogs PTH(5-34) and PTH(7-34) neither increased cAMP
      production in MS1 cells nor regulated RANKL or OPG mRNA. Reciprocal RANKL/OPG
      mRNA regulation was induced in MS1 cells by PTH(3-34) but only at high
      concentrations that also increased cAMP. The highly PKA-selective PTH analog
      [Gly1,Arg19]human PTH(1-28) exerted effects similar to PTH(1-34) on RANKL and OPG
      mRNAs and on osteoclast formation, both in MS1/spleen cell cocultures and in
      normal murine bone marrow cultures. The direct PKC stimulator 12-O
      tetradecanoylphorbol-13-acetate (PMA) did not induce RANKL mRNA in MS1 cells, but
      it did up-regulate OPG mRNA and also antagonized osteoclast formation induced by
      PTH(1-34) in both MS1/spleen cocultures and normal bone marrow cultures. Thus,
      cAMP/PKA signaling via the PTH1R is the primary mechanism for controlling RANKL
      dependent osteoclastogenesis, although direct PKC activation may negatively
      regulate this effect of PTH by inducing expression of OPG.

PMID- 12211439
TI  - Differential regulation of chemokine secretion in tuberculous and staphylococcal
      osteomyelitis.
AB  - Bone infection or osteomyelitis is characterized by uncontrolled inflammation and
      destructive bone loss although little is known about immunopathogenesis of
      infection. We investigated control of chemokine secretion from osteoblasts
      infected with either Mycobacterium tuberculosis, which normally elicits a
      granulomatous host response, or Staphylococcus aureus, which drives a host
      response dominated by neutrophil influx. We show that M. tuberculosis infection
      of cultured and primary osteoblasts induces extensive secretion of the chemokines
      interleukin (IL)-8, inducible protein (IP) 10, RANTES, and monocyte
      chemoattractant protein (MCP) 1 within 72 h (1630 +/- 280 pg/ml per 4 x 10(5)
      cells, 74,130 +/- 8480 pg/ml per 4 x 10(5) cells, 18,330 +/- 3040 pg/ml per 4 x
      10(5) cells, and 138,670 +/- 13,340 pg/ml per 4 x 10(5) cells, respectively, for
      MG-63 osteoblasts). S. aureus infection also results in secretion of these
      chemokines but secretion is delayed and of lesser magnitude (210 +/- 10 pg/ml per
      4 x 10(5) cells, 11,570 +/- 1240 pg/ml per 4 x 10(5) cells, 930 +/- 34 pg/ml per
      4 x 10(5) cells, and 13,770 +/- 720 pg/ml per 4 x 10(5) cells for IL-8, IP-10,
      RANTES, and MCP-1, respectively). The minimal up-regulation of secretion of the
      neutrophil attractant IL-8 in staphylococcal infection is both striking and
      unexpected. In both infections, chemokine secretion was dependent on the presence
      of live organisms. Differences in kinetics and magnitude of chemokine secretion
      are associated with distinct patterns of mRNA expression, as assessed by
      ribonuclease protection assay (RPA) and reverse-transcription polymerase chain
      reaction (RT-PCR). In addition, nuclear localization of the transcription factor
      activator protein (AP) 1 in M. tuberculosis-infected osteoblasts also is distinct
      as compared with S. aureus-infected cells. In summary, this study shows that
      osteoblasts have an important pathogen-specific role in control of chemokine gene
      expression and secretion during the human immune response to osteomyelitis.

PMID- 12211440
TI  - Direct effect of acute metabolic and respiratory acidosis on parathyroid hormone
      secretion in the dog.
AB  - Because both metabolic (Met Acid) and respiratory acidosis (Resp Acid) have
      diverse effects on mineral metabolism, it has been difficult to establish whether
      acidosis directly affects parathyroid hormone (PTH) secretion. Our goal was to
      determine whether acute Met Acid and Resp Acid directly affected PTH secretion.
      Three groups of dogs were studied: control, acute Met Acid induced by HCl
      infusion, and acute Resp Acid induced by hypoventilation. EDTA was infused to
      prevent acidosis-induced increases in ionized calcium, but more EDTA was needed
      in Met Acid than in Resp Acid. The PTH response to EDTA-induced hypocalcemia was
      evaluated also. Magnesium needed to be infused in groups receiving EDTA to
      prevent hypomagnesemia. The half-life of intact PTH (iPTH) was determined during
      hypocalcemia when PTH was measured after parathyroidectomy. During normocalcemia,
      PTH values were greater (p < 0.05) in Met Acid (92 +/- 19 pg/ml) and Resp Acid
      (77 +/- 22 pg/ml) than in controls (27 +/- 5 pg/ml); the respective pH values
      were 7.23 +/- 0.01, 7.24 +/- 0.01, and 7.39 +/- 0.02. The maximal PTH response to
      hypocalcemia was greater (p < 0.05) in Met Acid (443 +/- 54 pg/ml) than in Resp
      Acid (267 +/- 37 pg/ml) and controls (262 +/- 48 pg/ml). The half-life of PTH was
      greater (p < 0.05) in Met Acid than in controls, but the PTH secretion rate also
      was greater (p < 0.05) in Met Acid than in the other two groups. In conclusion,
      (1) both acute Met Acid and Resp Acid increase PTH secretion when the ionized
      calcium concentration is normal; (2) acute Met Acid may increase the bone efflux
      of calcium more than Resp Acid; (3) acute Met Acid acts as a secretogogue for PTH
      secretion because it enhances the maximal PTH response to hypocalcemia.

PMID- 12211441
TI  - Transcription from the tartrate-resistant acid phosphatase promoter is negatively
      regulated by the Myc oncoprotein.
AB  - TRAP, a characteristic marker of osteoclast differentiation, is an enzyme that
      plays an active role in the process of bone resorption. Despite the importance of
      TRAP in osteoclast biology, the components involved in the transcriptional
      regulation of this gene are largely unknown. This study investigated the
      regulation of TRAP transcription by the Myc oncoprotein in three different cell
      types. A series of nested TRAP promoter deletion constructs were cotransfected
      into P388D1 murine macrophages and C3H10T1/2 murine embryonic fibroblasts along
      with a backbone plasmid control or expression plasmids containing v-Myc, c-Myc,
      or an inactive v-Myc protein construct (delta84/NLS). Both v-Myc and c-Myc
      negatively regulated transcription from the TRAP promoter in P388D1 and C3H10T1/2
      cells, 90% and 50%, respective to cell type and amount of endogenous Myc protein,
      and delta84/NLS had no effect. The functional Myc-responsive element(s) within
      the TRAP promoter was localized to a region between -436 and +1 bp, which
      contains two putative Myc-inhibitory binding sites coincident with an initiator
      element (Inr) at -116 bp and -18 bp. Conversely, in the HD-11EM chicken v-Myc
      transformed preosteoclast cell line, the full-length TRAP promoter transcription
      was increased when endogenous v-Myc levels were decreased in response to
      pretreatment of these cells with 1alpha,25-dihydroxyvitamin D3
      [1alpha,25(OH)2D3]. This report provides the first evidence of the specific
      regulation of TRAP at the transcriptional level by Myc, a transcription factor
      that is normally expressed at relatively high levels in preosteoclasts and other
      myelomonocytic cells and suggests that Myc plays an active role in suppressing
      the transcription of a mature osteoclast selective gene.

PMID- 12211442
TI  - Transforming growth factor-beta1 negatively regulates crystallin expression in
      teeth.
AB  - Previously, we have reported that targeted overexpression of transforming growth
      factor (TGF) beta1 in the teeth of the transgenic mice (dTGF-beta1) results in a
      novel tooth phenotype phenomimicking the most prevalent tooth disorders in human.
      This phenotype was associated with discoloration and attrition of teeth due to
      defective mineralization. Here, we report a novel expression of crystallin family
      members in developing mouse teeth and its regulation by TGF-beta1 in these
      transgenic mice. AlphaB- and beta-crystallins were found to be elevated in dTGF
      beta1 mouse teeth, whereas gamma-crystallin (gammaB, gammaC, and gammaF), a
      marker of cell differentiation, was significantly reduced. Because crystallins
      are believed to be stress-related proteins, their expression in teeth implicates
      them in a similar role because teeth are constantly subjected to physical
      friction and temperature fluctuations.

PMID- 12211443
TI  - Genome screen for quantitative trait loci contributing to normal variation in
      bone mineral density: the Framingham Study.
AB  - A genome-wide scan was performed in a randomly ascertained set of 330 extended
      families from the population-based Framingham Study to identify chromosomal
      regions possibly linked to bone mineral density (BMD). A set of 401
      microsatellite markers was typed at a 10-centimorgan (cM) average density
      throughout the genome. BMD was measured at the femoral neck, trochanter, Ward's
      area, and lumbar spine in 1557 participants of both Framingham cohorts. BMDs were
      adjusted for age, body mass index (BMI), height, alcohol, caffeine, calcium and
      vitamin D intakes, smoking, physical activity, and estrogen use in women within
      each sex and cohort. Strong heritabilities (values between 0.543 and 0.633) were
      found for the adjusted BMD at all sites. Two-point and multipoint quantitative
      linkage analyses were performed for each BMD site using the maximum likelihood
      variance components method. By two-point screening, loci of suggestive linkage
      were identified on chromosomes 6 and 21, with the maximum log10 of the odds ratio
      (LOD) scores of 2.34 for the trochanter at D21S1446 and 2.93 for the femoral neck
      at D6S2427. Lumbar spine BMD had maxima at D6S2427 (LOD = 1.88) and at D12S395
      (LOD = 2.08). Multipoint linkage analysis revealed suggestive linkage of
      trochanteric BMD at a broad (approximately 20 cM) interval on chromosome 21q,
      with the peak linkage close to D21S1446 (LOD = 3.14). LOD scores were 2.13 at
      8q24 with Ward's BMD and 1.92 at 14q21.3 with lumbar spine BMD. This largest
      genome screen to date for genes underlying normal variation in BMD, adjusted for
      a large number of covariates, will help to identify new positional candidate
      genes, otherwise unrecognized.

PMID- 12211445
TI  - Biofiltration of ammonia gas with sponge cubes coated with mixtures of activated
      carbon and zeolite.
AB  - Removal of ammonia gas was investigated using a biofilter system packed with
      small cubes of polyurethane sponge that were coated with a powder mixture of
      activated carbon and natural zeolite. Experimental tests and measurements include
      removal efficiency, pH, metabolic products of ammonia and kinetic analysis. A
      removal efficiency over 90% can be obtained with ammonia concentrations below 150
      ppm and at contact times above 23 sec.The ammonia adsorbing power of the present
      biocarrier can protect the biofilter system from a high ammonia shock loading in
      the feed. The maximum removal rate, Vm, obtained from the kinetic analysis is
      8.47 g N (kg carrier)(-1) day(-1) and the saturation constant Ks is 50.36 ppm.
      Nitrite is produced dominantly during the entire experiments. The cell number of
      nitrifying bacteria is 1.58 x 10( cell (g carrier)(-1). The present synthetic bio
      carrier is considered to be one of the best among bio-carriers that have been
      used for the biofiltration of ammonia.

PMID- 12211444
TI  - Tryptophan missense mutation in the ligand-binding domain of the vitamin D
      receptor causes severe resistance to 1,25-dihydroxyvitamin D.
AB  - In this study, two related young children, brother and sister, exhibited severe
      vitamin D-resistant rickets without alopecia. Sequence analysis of the total
      vitamin D receptor (VDR) cDNA from skin fibroblasts revealed a substitution of
      the unique tryptophan of the VDR by arginine at amino acid 286 (W286R). Cultured
      skin fibroblasts of the two patients expressed normal-size VDR protein
      (immunocytochemistry and Western blotting) and normal length VDR mRNA (Northern
      blotting). But, these fibroblasts, as well as COS-7 cells transfected with the
      W286R mutant, failed to bind 3H 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The
      tryptophan substitution did not affect VDR trafficking toward the nucleus but
      abolished the 24-hydroxylase gene response to 1,25(OH)2D3, even at 10(-6) M
      concentrations. In conclusion, this case report of a new family with hereditary
      vitamin D-resistant rickets (HVDRR) emphasizes the crucial role of the VDR
      tryptophan for ligand binding and for transactivation of 1,25(OH)2D3 target
      genes. It clearly shows the clinical significance of this VDR amino acid for
      calcium homeostasis and bone mineralization. This observation suggests further
      that the presence of a stable VDR-bound ligand may not be obligatory for normal
      hair follicle development.

PMID- 12211446
TI  - Calibration and validation of activated sludge model No.2d for Spanish municipal
      wastewater.
AB  - Activated Sludge Model No. 2d (ASM2d) was validated with data obtained from pilot
      scale plant treating municipal wastewater from the city of Valencia (Spain).
      First of all, ASM2d was calibrated using experimental data from anaerobic, anoxic
      and aerobic batches. A set of kinetic and stoichiometric parameters resulted from
      these assays. Differences between the values obtained and default values proposed
      in ASM2d can be explained by the presence of glycogen accumulating organisms
      (GAOs). The calibrated model was then used to simulate results from a pilot
      plant. Simulation using the set of parameters obtained accurately reproduces
      experimental results. This paper also presents a detailed procedure to estimate
      kinetic and stoichiometric parameters for heterotrophic, autotrophic and
      polyphosphate accumulating bacteria.

PMID- 12211447
TI  - Fermentation of municipal primary sludge: effect of SRT and solids concentration
      on volatile fatty acid production.
AB  - Laboratory bench-scale experiments were conducted to investigate the performance
      of primary sludge fermentation for volatile fatty acids production. Primary
      sludges from two major wastewater treatment plants located in Valencia (Pinedo
      and Carraixet) were used. Experiments were performed at solids retention times
      between 4 and 10 days, and total volatile solids concentrations between 0.6% and
      2.8%. Operation at two temperatures (20 degrees C and 30 degrees C) was also
      checked. Results indicated the importance of feed sludge characteristics on
      volatile fatty acids yields, being approximately double for the Carraixet
      wastewater treatment plant sludge than for the Pinedo plant. In both cases,
      higher volatile fatty acids yields were observed at higher total volatile solids
      concentrations. Solids retention times above 6 days scarcely improve volatile
      fatty acids yields, while experiments conducted at 4 days of solids retention
      times show an important decrease in volatile fatty acids yields. On raising
      temperature an increase in volatile fatty acids yields was observed, mainly due
      to an improvement in the hydrolysis of particulate organic matter.

PMID- 12211448
TI  - Remediation of fine fractions of dredged sediments by flotation.
AB  - In the Netherlands, large quantities of contaminated dredged sludge have to be
      deposited or treated in the near future. Because of the large amounts of small
      particles involved, successful treatment is difficult. In this study a new
      flotation method on laboratory scale was used as an alternative remediation
      technique. Dissolved air was used to create small bubbles. Tests were performed
      with the finest fractions of sediments of Overschie (Rotterdam) and Petrol Harbor
      (Amsterdam) sludges contaminated with Polycyclic Aromatic Hydrocarbons (PAH).
      Several agents and conditions were tested with respect to the flotation
      efficiency. For Overschie sludge the best results were obtained without collector
      and SDS as frother. The PAH concentration in the Froth was up to 8 times higher
      than that in the non-floating fractions. The collected amount of dry matter in
      the froth was around 13%. With a two step flotation, the PAH concentration of the
      non-floating "clean" fraction was reduced from 240 mg (kg d m(-1)) to 99 mg (kg d
      m(-1)). For Petrol Harbor sludge the best results were obtained with the alcohol
      based frothers Aerofroth and Montanol. The flotation was less selective than with
      Overschie sediment. Around 50%. solids were collected in the froth and the PAH
      concentration in the Froth was around 2 times higher than in the Settled fraction
      and 3-5 times higher than in the fraction Remains.

PMID- 12211449
TI  - Physicochemical characterization of UASB sludge with different size
      distributions.
AB  - Upflow anaerobic sludge blanket (UASB) sludges developed in UASB system are used
      to treat various wastewaters. Methanogenic microbial consortia in UASB sludges
      convert organic compounds to methane under anaerobic conditions. Sludge granules
      are developed by self-granulation of microorganisms and dynamic balance between
      granule growth and decay results in coexistence of UASB sludges with different
      sizes in the reactor. In this study, UASB sludges taken from a laboratory-scale
      UASB reactor were classified into 4 groups based on their diameters and their
      physicochemical characteristics were investigated. Each group was analyzed for
      settling ability, specific methanogenic activity (SMA), and elemental content.
      Settling ability was proportional to diameter of UASB sludges, suggesting
      effective detainment of larger granular sludges in the reactor. When acetate o r
      glucose was used as a substrate, a ll groups showed a relatively slight
      difference in SMA. However SMA with a volatile fatty acid mixture showed a
      significant increase with sludge diameter, suggesting better establishment of
      syntrophic relationship in larger granular sludges. Larger granular sludges
      showed a higher value of SMA upon environmental changes(ie., pH, temperature, or
      toxicant concentration). Comparative analysis of elemental contents showed that
      content (dry weight %) of most tested elements (Fe, Ca, P, Zn, Ni, and Mn)
      decreased with sludge diameter, suggesting that the elements could be important
      for initial granulation. Taken together, this study verified experimentally that
      physicochemical properties of UASB sludges are related to UASB sludge size
      distributions. Overall results of physicochemical characterization supports that
      larger granular sludges are better applicable to UASB systems.

PMID- 12211450
TI  - Mercury speciation in sediments of a tropical coastal environment.
AB  - The speciation of mercury in tropical coastal areas, although scarcely studied,
      has presented an odd behaviour when compared with the results obtained in
      temperate environments. In this work, we measured the concentrations of mercury
      species (mercuric mercury, methyl-mercury and dimethyl-mercury) in the sediments
      of Sepetiba Bay (Brazil) and compared these with geochemical parameters. Twenty
      eight sediment samples were extracted in an open microwave system and mercury
      speciation was carried out by ethylation, cryogenic focusing, gas chromatography
      and quartz furnace atomic absorption spectrometry. Fraction < 63 microm, organic
      carbon and total sulphur contents and redox potential were measured in order to
      outline the geochemical characteristics of the sediments. While mercuric mercury
      presented concentrations ranging between 22.65 and 134.61 ng g(-1), methyl
      mercury concentrations ranged between < 2.0 and 4.4 ng g(-1). Only a few dimethyl
      mercury concentrations were relatively high (up to 14.6 ng g(-1)). The results of
      mercuric mercury presented an unexpected positive correlation with sulphur
      contents showing that mercury is forming stable sulphide complexes, even under
      very reducing conditions. This would render mercury available for t he formation
      of methyl- or dimethyl-mercury that would be both fixed in the sediments and
      volatilised.

PMID- 12211451
TI  - A degradation and toxicity study of three textile reactive dyes by ozone.
AB  - Textile reactive dyes are very recalcitrant to biodegradation, causing aesthetic,
      acute and chronic toxicity problems in receiving waters. In this study, we
      present the degradation of three different reactive dyes (Reactive Black 5,
      Reactive Blue 19 and Reactive Blue 21) by ozone, at two different pH conditions.
      The ozonation process achieved a very fast decoloration rate for the studied
      dyes. The influence of pH in the ozonation of these dyes was only significant for
      Reactive Black 5. The toxicity of dyes, after pre-treatment, was evaluated using
      Vibrio fisheri (microtox). There was little change in toxicity for Reactive Black
      5, but there was a reduction for Reactive Blue 19. A significant increase in
      toxicity for Reactive Blue 21 was verified, caused by the increase in the
      bioavailability of th e cooper ion that was in the complexed form before the
      treatment with ozone.

PMID- 12211452
TI  - Levels and distribution patterns of polychlorinated biphenyl congeners in surface
      sediments from Galicia coast (Northwestern, Spain) according to granulometric
      characteristics.
AB  - In order to know distribution patterns of polychlorinated biphenyl congeners in
      the marine environment from Galida, PCBs n degrees 31, 28, 52, 101, 118, 153,
      105, 138, 156 and 180 were isolated by Soxhlet extraction from three fractions of
      different particle size (<0.063 mm, 0.063-0.2 mm and >0.2 mm) in surface marine
      sediments; the quantification was performed using GC-MS and GC-ECD. Distribution
      of PCB congeners was shifted in favour of higher chlorinated compounds (CBs
      138,153 and 180) and highly correlated to TOC content. In general, the finest
      fractions (<0.063 mm) of sediment presented the highest loadings of PCBs, only
      the sediment from As Pias zone exhibited the highest concentration of chlorinated
      congeners in the coarsest fraction. CB 52 concentration, slightly volatile
      compound, was related to water temperature. By means of multivariate techniques
      of data exploration as hierarchical duster analysis and principal components
      analysis, sediment samples from un-contaminated and slightly contaminated areas
      were clearly separated; groupings between samples from nearby zones appeared.

PMID- 12211453
TI  - ASExpert: an integrated knowledge-based system for activated sludge plants.
AB  - The activated sludge process is commonly used for secondary wastewater treatment
      worldwide. This process is capable of achieving high quality effluent. However it
      has the reputation of being difficult to operate because of its poorly understood
      biological behaviour, variability of input flows and the need to incorporate
      qualitative data. To augment this incomplete knowledge with experience, knowledge
      based systems were introduced in the 1980s however they didn't receive much
      popularity. This paper presents the Activated Sludge Expert system (ASExpert),
      which is a rule-based expert system plus a complete database tool proposed for
      use in activated sludge plants. The paper focuses on presenting the system's main
      features and capabilities to revive the interest in knowledge-based systems as a
      reliable means for monitoring plants. Then it presents the methodology adopted
      for ASExpert validation along with an assessment of testing results. Finally it
      concludes that expert systems technology has proved its importance for enhancing
      performance, especially if in the future it is integrated to a modern control
      system.

PMID- 12211454
TI  - Treatment of effluents of poultry slaughterhouse with aluminum salts and natural
      polyelectrolytes.
AB  - A mixture of aluminum salts and natural polyelectrolytes, extracted from the
      cactus Opuntia ficus indica, has been used for cleaning of wastewater from
      poultry slaughterhouse. The aggregation and settling properties of colloids and
      complex organics such as oil, grease, fats, proteins, and suspended solids, was
      increased if compared with conventional methods of wastewater treatment using
      only aluminum or iron sulfate. A mixture of aluminum salt in a concentration
      range of 300 to 600 mg l(-1) and natural polyelectrolytes of 0.6 to 0.8 mg l(-1)
      was used for flocculation and coagulation. The combination of coagulant and
      natural polyelectrolytes was able to remove chemical oxygen demand (86%), oil and
      grease (93%), turbidity (89%), and suspended solids (93%). Methanization activity
      was also investigated for the effluents in natura.

PMID- 12211455
TI  - Photocatalyzed mineralization of kraft black liquor on ZnO/Fe2O3 coupled
      semiconductor.
AB  - Photocatalysis using ZnO-Fe2O3 coupled catalyst removed partially the organic
      matter dissolved in kraft black liquor obtained from pinus wood cooking. The
      photo-assisted oxidation using different ZnO/Fe2O3 ratios was studied following
      the CO, evolution during the course of the reaction. A synergy of the composite
      improves the mineralization observed. The optimal ZnO to Fe2O3 ratio varied from
      0.5 to 0.7 which allowed the highest mineralization rates.

PMID- 12211456
TI  - Micromechanical measurement of active sites on silicon nitride using surface free
      energy variation.
AB  - We have investigated chemical reactions between adsorbed water and active sites
      on a silicon nitride surface as a function of temperature and relative humidity
      using microcantilevers. Effects that might produce a change in the response of
      the microcantilever, such as a mass adsorption, surface tension of the adsorbed
      water, and changes in thermal conductivity, were systematically investigated. It
      is shown that the judicious choice of experimental conditions could make these
      effects essentially inconsequential in comparison with the instrument response
      produced by the change in free surface energy of the microcantilever due to the
      chemical reactions. Using this method, the variation in free surface energy when
      changing from dry to high humidity conditions was found and the number of active
      sites that reacted was estimated. This method may be extended to other problems
      for use in determining surface free energy change and thus the density of
      reactant sites under different conditions of interest.

PMID- 12211458
TI  - Mechanical property measurements of nanoscale structures using an atomic force
      microscope.
AB  - This paper describes nanometer-scale bending tests of fixed single-crystal
      silicon (Si) and silicon dioxide (SiO2) nanobeams using an atomic force
      microscope (AFM). The technique is used to evaluate elastic modulus of the beam
      materials and bending strength of the beams. Nanometer-scale Si beams with widths
      ranging from 200 to 800 nm were fabricated on a Si diaphragm using field-enhanced
      anodization using an AFM followed by anisotropic wet etching. Subsequent thermal
      oxidation of Si beams was carried out to create SiO2 beams. Results from the
      bending tests indicate that elastic modulus values are comparable to bulk values.
      However, the bending strength appears to be higher for these nanoscale structures
      than for large-scale specimens. Observations of the fracture surface and
      calculations of the crack length from Griffith's theory appear to indicate that
      the maximum peak-to-valley distance on the beam top surfaces influence the values
      of the observed bending strengths.

PMID- 12211457
TI  - Read/write mechanisms and data storage system using atomic force microscopy and
      MEMS technology.
AB  - Information storage system that has a potentially ultrahigh storage density based
      on the principles of atomic force microscopy (AFM) has been developed. Micro
      electro-mechanical systems (MEMS) technology plays a major role in integration
      and miniaturization of the standard AFM. Its potential application for ultrahigh
      storage density has been demonstrated by AFM with a piezoresponse mode to write
      and read information bits in ferroelectric Pb(Zr(x)Ti(1 - x))O3 films. With this
      technique, bits as small as 40 nm in diameter have been achieved, resulting in a
      data storage density of simply more than 200 Gb/in2. Retention loss phenomenon
      has also been observed and investigated by AFM in the piezoresponse mode.
      Finally, local piezoelectric measurements of PZT films by different processing
      technologies are discussed in detail.

PMID- 12211459
TI  - Observation of recording pits on phase-change film using a scanning probe
      microscope.
AB  - A phase-change film is a key material for optical data storage media such as
      rewritable compact disks (CD-RW) and digital versatile disk random access memory
      (DVD-RAM). Data pits are recorded as differences in crystal state (crystallized
      state vs. amorphous state) on phase-change film. It is very important to
      distinguish the crystal state difference in a very small area for material
      research of phase-change film. Measuring size and shape of recorded data pits is
      also very important for the development to achieve good data reliability and high
      data density of optical data storage media. The crystal state difference in very
      small areas of phase-change film is successfully observed by Kelvin probe force
      microscopy (KFM) and scanning near-field optical/atomic force microscopy (SNOAM).
      The advantage of KFM and SNOAM for measuring physical property differences in a
      very small area is demonstrated.

PMID- 12211460
TI  - Current and potential characterization on InAs nanowires by contact-mode atomic
      force microscopy and Kelvin probe force microscopy.
AB  - We fabricated InAs nanowires on GaAs giant step structures, and studied their
      surfaces by two methods; one was current detection by contact-mode atomic force
      microscopy, and the other was surface potential measurement by Kelvin probe force
      microscopy (KFM). In the current detection method, the regions where the large
      current flowed were distributed along the step edges, and these regions agreed
      well with the expected distribution of InAs. This result confirms that the InAs
      nanowires were formed along the GaAs giant step edges. The KFM measurements
      showed that the potential value became more negative along each step edge, where
      the InAs nanowire was expected to be formed. The surface potential of the InAs
      nanowires is more negative than that of the surrounding GaAs, which may result
      from the electron accumulation in the InAs nanowires.

PMID- 12211461
TI  - An atomic force microscope-based investigation of vertical transport through
      GaAs/GaAlAs/InAlAs/GaAs step-barrier heterostructures.
AB  - Study of vertical transport through heterostructures consisting of single,
      double, or multiple quantum barriers is of both fundamental and technological
      interest. While extensive data regarding electron transport is available for
      single- and double-barrier structures, relatively less information is available
      for transport through step-barrier structures. In this paper, we present results
      from a study of room temperature vertical transport through a
      GaAs/GaAlAs/InAlAs/GaAs multistep-barrier heterostructure. A typical atomic force
      microscope has been adapted to perform transport measurements, thus allowing
      precise control of the physical location of the region of measurement. I-V
      measurements reveal negative differential resistance (NDR) peaks, thus confirming
      the formation of resonant states in a triangular well created when a voltage bias
      is applied across the step barrier. I-V curves have also been calculated by
      numerically solving the Schrodinger wave equation for this step-barrier
      structure. Comparison between the measured and calculated I-V curves shows
      reasonable agreement in the number of NDR peaks. However, discrepancies exist
      between the measured and calculated values for the voltages at which these NDR
      peaks occur. Some possible reasons for these discrepancies are discussed in this
      work.

PMID- 12211462
TI  - DC electric-field-induced DNA stretching for AFM and SNOM studies.
AB  - An effective method of DNA stretching on mica surfaces is proposed for an
      extremely low concentration of DNA. The method is based on an electric field and
      well applied on the concentration range from 57 x 10(-3) to 57 x 10(-6) ng/ml.
      The stretching exists in a gap between positive and negative electrodes. The
      difference in the stretching efficiency among the different surfaces of bare
      mica, Mg2+ soaked mica and AP-mica is discussed. The best performance of the
      stretching is found from the surface of AP-mica for the same experimental
      condition of sample concentration and applied voltage. Finally, from a Scanning
      near-field optical microscope image, it is found that well-stretched DNA
      molecules have shown more similar optical resolution, which is inferred from an
      optical fiber probe, itself.

PMID- 12211463
TI  - Surface potential contrasts between silicon surfaces covered and uncovered with
      an organosilane self-assembled monolayer.
AB  - Surface potentials of Si substrates covered with a organosilane self-assembled
      monolayers (SAMs) were measured with reference to the substrate uncovered with
      the SAM using Kelvin probe force microscopy. Based on a photolithographic
      technique, the reference surface was prepared in a micrometer scale on each of
      the samples. SAMs were prepared from n-octadecyltrimethoxysilane [ODS:
      CH3(CH2)17Si(OCH3)3], 3,3,3-trifluoropropyltrimethoxysilane [FAS3:
      CF3(CH2)2Si(OCH3)3], heptadecafluoro-1,1,2,2-tetahydro-decyl-1-trimethoxysilane
      [FAS17: CF3(CF2)7(CH2)2Si(OCH3)3] or n-(6-aminohexyl) aminopropyltrimethoxysilane
      [AHAPS: H2N(CH2)6NH(CH2)3Si(OCH3)3) by chemical vapor deposition. Potentials of
      the surfaces covered with ODS-, FAS3- and FAS17-SAMs became more negative than
      the uncovered Si substrate, while the surface covered with AHAPS-SAM showed a
      more positive surface potential than the reference. The potential contrasts of
      these SAMs to the reference were -25, -170, -225 and +50 mV for ODS-, FAS3-,
      FAS17- and AHAPS-SAMs, respectively. These results almost agreed with potentials
      expected from the dipole moments of the corresponding precursor molecules
      estimated by ab initio molecular orbital calculation, except for FAS3-SAM.
      Despite FAS3 molecule having a larger dipole moment than FAS17 molecule, the
      surface potential contrast of FAS3-SAM was smaller than that of FAS17-SAM, since
      surface coverage of FAS3-SAM was relatively incomplete compared with the other
      SAMs.

PMID- 12211464
TI  - Direct observation of polyhydroxyalkanoate chains by atomic force microscopy.
AB  - Atomic force microscopy in the tapping mode was used to investigate aqueous
      acetone-treated polyhydroxyalkanoate (PHA) inclusions freshly isolated from a
      recombinant bacterium. The PHA is a copolymer containing about 95 mol% 3
      hydroxybutyrate units while the rests are units of 3-hydroxyhexanoate, 3
      hydroxyoctanoate, 3-hydroxydecanoate, and 3-hydroxydodecanoate. Polymer chains
      extending to several micrometers in length were observed on glass cover slips
      upon the evaporation of the aqueous acetone. The polymer chains seem to exist in
      the form of fibrillar aggregates. The height of the microfibrils was about 1 nm.
      Upon prolonged standing at ambient conditions, the microfibrils dissociated into
      finer strands of about 0.5 nm in height. The results suggest that biosynthesized
      PHA are stored in the inclusions in an amorphous state but with minimal chain
      entanglement. This is possible because the PHA chains exist in the form of
      fibrillar aggregates that may be the product of a special biosynthesis mechanism.

PMID- 12211465
TI  - A study of positive charge effect on AFM anodization lithography using metal
      phosphate monolayers.
AB  - Monolayer films of metal phosphate were prepared by sequential adsorption of
      phosphoric acid (PA) and metal ions (Zr4+ or Ca2+). The monolayer formation was
      confirmed and characterized by ellipsometry and atomic force microscopy (AFM).
      Nanometer-scale patterning on the self-assembled metal phosphate films has been
      achieved using AFM. The difference in AFM lithography on positively charged
      surfaces in the case of Zr4+ and Ca2+ ions was investigated and summarized. Since
      the presence of the positive charges allows electrons to move from a tip to a
      layer easily, the lithographic process initiates at a lower voltage in the layer
      of Zr2+ phosphate than in the layer of Ca phosphate or PA. Other lithographic
      results on metal phosphate layers were compared with those on a monolayer of PA.

PMID- 12211466
TI  - AFM nanolithography on a mixed LB film of hexadecylamine and palmitic acid.
AB  - An evenly mixed Langmuir film of hexadecylamine (HDA) and palmitic acid (PA) was
      prepared on the air-water interface and transferred to a Si substrate for the
      fabrication of nano-sized patterns. Vibrational spectrum of the transferred film
      shows that all acid groups of PAs were deprotonated and amine groups of HDAs were
      protonated by an acid-base reaction. The effect of mixing ratios in atomic force
      microscopy anodization lithography on the mixed films was investigated in terms
      of the line width of the protruded pattern. While the line width fabricated on PA
      film was 221 nm, the width on the mixed film was reduced to 84 nm under the same
      lithographic conditions. It is believed that the phenomenon was originated from
      the mixed structure from the interaction of HDA and PA. The chemical composition
      difference caused by the presence of ammonium cation in resist resulted in
      reducing the line width fabricated in the mixed Langmuir-Blodgett film.

PMID- 12211467
TI  - Orientation and relocation of biphenyl thiol self-assembled monolayers under
      sliding.
AB  - Recent studies have emphasized the use of biphenyl thiol (BPT) monolayers as a
      resist in electron lithography. In this paper, friction and wear properties of
      BPT monolayers have been studied by atomic force microscopy. The BPT molecular
      chains are compliant and experience orientation under normal load, which in turn
      reduces the friction force. During sliding it is observed that after the first
      several scans, the friction force of BPT is significantly reduced, but the
      surface height does not show any apparent change. These observations suggest that
      the orientation is reversible and can be facilitated by initial sliding.
      Relocation and accumulation of BPT occurs during the first several scans, which
      lead to the formation of larger terrace. Based on the wear studies of a single
      BPT terrace, it is found that the wear lives of self-assembled monolayers
      increase exponentially with terrace size.

PMID- 12211468
TI  - Investigation of nanotribological properties of self-assembled monolayers with
      alkyl and biphenyl spacer chains (invited).
AB  - Understanding the relationships between molecular structure and nanotribological
      performance of self-assembled monolayers (SAMs) are quite important for molecular
      tailoring for efficient lubrication. For this purpose, SAMs, having alkyl and
      biphenyl spacer chains with different surface terminal groups (-CH3, -COOH, and 
      OH), and head groups (-SH and -OH), were prepared. The influence of spacer
      chains, surface terminal groups, and head groups on adhesion, friction and wear
      properties were investigated by contact mode atomic force microscopy (AFM). The
      relative stiffness of SAMs was determined by force modulation mode AFM and
      indentation experiments using load-displacement curves. The friction properties
      of SAMs are explained using a molecular spring model in which local stiffness
      governs the friction properties. Micropatterned SAMs specimen were fabricated and
      studied to verify the molecular spring model. The influence of relative humidity,
      temperature and velocity on adhesion and friction was studied. The failure
      mechanisms of SAMs and substrates were investigated by wear and continuous
      microscratch AFM technique. Based on these studies, the adhesion, friction and
      wear mechanisms of SAMs at molecular scale are discussed.

PMID- 12211469
TI  - Effect of aggregation state on nanotribological behaviors of organosilane
      monolayers.
AB  - Nanotribological behaviors of organosilane monolayers prepared by the Langmuir
      Blodgett (LB) and chemisorption methods are discussed in terms of their
      aggregation states. Aggregation structure of the LB n-octadecyltrichlorosilane
      (OTS-C18) monolayers changed from a rectangular to an amorphous phase via a
      hexagonal phase with increasing temperature. A distinct lateral force decrease
      accompanies the phase transition. The LB alkyltrichlorosilane monolayers with
      longer alkyl chains were in a crystalline state at 293 K. The lateral force of
      the LB alkyltrichlorosilane monolayers at 293 K increased with increasing chain
      length. The n-triacontyltrichlorosilane LB monolayer (TATS-C30) in a rectangular
      phase showed higher lateral force than that of the alkyltrichlorosilane with
      shorter alkyl chains in a hexagonal phase. The lateral force of the OTS-C18
      monolayer prepared by the LB method was higher than that of the chemisorbed one
      because of the higher packing density of alkyl chain for the LB monolayer, though
      both monolayers are in a hexagonal phase at 293 K. A large increase in lateral
      force was observed for the 18-nonadecenyltrichlorosilane (NTS) after oxidation of
      vinyl end groups.

PMID- 12211470
TI  - Nanochemical surface analyzer in CMOS technology.
AB  - We have developed an atomic force microscopy (AFM) cantilever system, fabricated
      using a standard CMOS process and a few post-processing steps, capable of
      detecting the difference between hydrophilic and hydrophobic samples for the
      purpose of nanochemical surface analysis. The fully integrated cantilever
      comprises a thermal actuator for cantilever deflection and a Wheatstone bridge to
      sense cantilever bending, thus obviating the need for cumbersome laser detection
      and external piezoelectric drives. Glass microspheres have been affixed to the
      cantilevers and, were either modified with a self-assembled monolayer to form
      hydrophobic tips, or left unmodified for hydrophilic tips. Force-distance curves
      have been used to measure the force between the functionalized/unfunctionalized
      tips and hydrophobic/hydrophilic sample surfaces. In an optimization step three
      different Wheatstone bridge sensors have been designed and characterized; best
      Wheatstone bridge sensitivity is 8.0 microV/nm with a 713 nm/mW actuator
      efficiency.

PMID- 12211471
TI  - Scanning surface potential microscopic studies of photo-voltaic Langmuir-Blodgett
      assemblies containing an A-S-D triad molecule.
AB  - Scanning surface potential microscopy was applied to detect the photo-voltaic
      response of Langmuir-Blodgett (LB) monolayer assemblies containing an amphiphilic
      A-S-D triad molecule (ASD) with two different concentrations. The triad acts as a
      charge separation unit in the same way as the photosynthetic reaction center. In
      addition, the photo-induced multistep electron transfer systems can be organized
      in the LB monolayers: first electrons and holes are separated across the
      monolayer through the ASD triads upon photo-excitation and then the resultant
      electrons and holes are further separated by lateral diffusion among the
      concentrated A and the D moieties, respectively. The change in surface potential
      was clearly observed on an LB assembly with the high ASD concentration in a mixed
      ASD monolayer with omega-tricosenoic acid (T) (the molar ratio of ASD:T = 1:5),
      while the photo-response could not be observed on an LB monolayer with the low
      ASD concentration (the molar ratio of ASD:T = 1:30). It was interesting to note
      that the average surface concentration of ASD in the latter diluted monolayer was
      decreased only to 6 of that of the former concentrated monolayer. If the photo
      response depended linearly on the ASD concentration, the surface potential would
      be readily detected in the latter monolayer. The nonlinearity can be attributed
      to the effect of succeeding lateral diffusion of the separated charges among the
      ASD triads. To clarify the effect of the lateral diffusion, the other type of LB
      assemblies, i.e., A/A-S-D double layers, was fabricated by alternate deposition
      of an additional acceptor (A) layer and the ASD layer. In the A/A-S-D assemblies,
      significant photo-induced surface potential change was observed with an A layer
      of a high A concentration (A:T = 1:2) even when the ASD concentration was low in
      the ASD layer (ASD:T = 1:30). This result supported an idea that the additional A
      layer enhanced lateral electron diffusion and resulted in electron accumulation
      in A layer and hole accumulation in the diluted ASD layer in the A/A-S-D system.

PMID- 12211472
TI  - Surface modification of an organosilane self-assembled monolayer on silicon
      substrates using atomic force microscopy: scanning probe electrochemistry toward
      nanolithography.
AB  - Organosilane self-assembled monolayers (SAMs) have been applied to resist
      materials for nanolithography based on scanning probe microscopy. An organosilane
      SAM was prepared on Si substrates from a precursor, that is
      octadecyltrimethoxysilane. Using an atomic force microscope with a conductive
      probe, current was injected from the probe into the SAM-covered Si substrate so
      that the SAM was locally degraded at the probe-contacting point. Nanoscale
      patterns drawn on the SAM was clearly imaged by lateral force microscopy. The
      patterning could be conducted in air while, in vacuum at the order of 10(-6)
      Torr, no detectable patterns were fabricated. The presence of adsorbed water at
      the probe/sample junction was confirmed to be crucial for the patterning of the
      SAM/Si. Its mechanism was, thus, ascribed to electrochemical reactions of both
      the SAM and Si with adsorbed water.

PMID- 12211473
TI  - Effect of temperature on friction observed between a Si3N4 tip and a
      dodecanethiol self-assembled monolayer on Au(1 1 1).
AB  - Recent computational studies (Phys. Rev. Lett. 70 (1993) 1960; Phys. Rev. B 62
      (2000) 17055) predicted that friction of ordered organic monolayer had
      characteristic dependence on temperature, where the maximum friction was observed
      around rotator transition point of the monolayer. This remained to be confirmed
      experimentally. Using a friction force microscope (FFM) combined with a
      temperature regulation module, we attempted to investigate such dependence on
      temperature (130 K-room temperature) on a self-assembled monolayer of
      dodecanethiol prepared on Au(1 1 1). The observed friction showed strong
      dependence on temperature and good agreement with the computational prediction.

PMID- 12211474
TI  - Imaging the proteins pseudoazurin and apo-pseudoazurin on gold by STM in air:
      effect of the bias voltage.
AB  - We have applied scanning tunnelling microscopy (STM) to the study of two
      proteins: pseudoazurin and apo-pseudoazurin. Both proteins adsorbed onto a Au (1
      1 1) surface are visible to STM individually, forming into layers and
      multilayers, with currents from about 55 to 600 pA. The images reproduce well the
      expected dimensions laterally but not in the z direction. The apparent height of
      the proteins varies with the voltage polarity, being higher at negative sample
      voltages. The bias also affects their shape. Negative sample voltages of more
      than 1.5 V orient the proteins present on a gold terrace in parallel rows. The
      layer of water adsorbed on surfaces in ambient conditions can be related to our
      results to explain the reduced z dimensions, the asymmetry with the voltage
      polarity and the alignment of proteins at voltages more negative than -1.5 V.

PMID- 12211475
TI  - A near-field microscopy study of submicron domain structure in a model lung
      surfactant monolayer.
AB  - The submicron domain structure of coexisting liquid condensed (LC) and liquid
      expanded (LE) phases in monolayers composed of palmitic acid and 20 wt% of a lung
      surfactant protein B fragment has been investigated. Near-field microscopy was
      used to simultaneously measure topography and fluorescence images of monolayers
      that were prepared at a surface pressure of 15 mN/m and a temperature of 22
      degrees C. The use of a fluorescently tagged peptide allowed for unambiguous
      determination of the peptide location in the two-component system. The LC and LE
      phases in the monolayers are measured on the submicron length scale. A 6-11 A
      height difference between the LC and LE phases was evident in the height images.
      Gradual transitions between the LC and LE domains were observed across a 1.3
      microm length scale in the near-field fluorescence images, but were significantly
      sharper in the simultaneously collected topography images and in the separately
      measured AFM images. These results may reflect the occurrence of peptide
      encroachment into the LC domains.

PMID- 12211476
TI  - Reversible stretching of a monomeric unit in a dimeric bovine carbonic anhydrase
      B with the atomic force microscope.
AB  - We have previously shown that a full stretching of native carbonic anhydrase B
      (CAB) using the atomic force microscope could not be achieved, presumably due to
      the presence of a 'knot' in the C-terminal region of the protein. When we used an
      engineered dimer of CAB, where the N-terminal monomeric unit (unit I) was
      expected to be 'knotless', we successfully recorded extension of the protein up
      to 110 nm which was long enough to account for the full extension of unit I
      monomer. In this paper we report that, by limiting the maximum length of
      extension to 90 nm extensions (corresponding to about 80 nm extension of the
      dimer and 70 nm of unit I), retractions of the polypeptide chain can be repeated
      cyclically without breaking the covalent crosslinking system. The force-extension
      curves obtained from the forward and reverse cycles of such experiments were
      almost perfectly superimposable with each other and with the corresponding part
      of the curves obtained from full extension experiments suggesting that the
      structure of unit I in the dimer was reversibly stretched and contracted. During
      the stretching of unit I of the dimer in either type of the experiments mentioned
      above, we occasionally observed a force peak having the force of about 0.5-0.7 nN
      when extension length reached 40-50 nm. We interpreted the appearance of such
      force peaks as an indication of formation of a tightly folded domain structure in
      unit I of CAB dimer.

PMID- 12211477
TI  - Use of AFM for imaging and measurement of the mechanical properties of light
      convertible organelles in plants.
AB  - We obtained topographic images of etioplasts and chloroplasts and measured their
      elasticity in a physiological buffer using an atomic force microscope (AFM) and
      found a possible correlation between the morphological and mechanical properties
      during the light conversion of etioplasts to chloroplasts. Alcian blue 8GX dye
      was found to be effective for immobilizing the plant organelles stably on a glass
      surface for AFM experiments. We employed the tapping-mode AFM with a cantilever
      soft enough to measure the elasticity of the organelles in a liquid solution. The
      best images of soft, spherical organelles were obtained using the tapping-mode
      AFM with oscillation at the thermal vibration frequency of the cantilever of
      around 3 kHz. Whereas etioplasts were found to be smooth-surfaced and stiff
      against compression by the AFM tip, before light conversion to chloroplasts, they
      became rough-surfaced and mechanically soft after exposure to light. The
      elasticity of etioplasts was 20 times higher than that of chloroplasts, probably
      reflecting changes in their inner structures.

PMID- 12211478
TI  - Combination of AFM with an objective-type total internal reflection fluorescence
      microscope (TIRFM) for nanomanipulation of single cells.
AB  - A new instrument was constructed by combining an objective-type total internal
      reflection fluorescence microscope with an atomic force microscope (AFM). Our
      purpose of constructing such an instrument is to detect and confirm the result of
      cellular level manipulations made with the AFM part through the detection system
      of the highly sensitive fluorescence microscope part. In this combination,
      manipulations are now possible from the nanometer to the micrometer scales and
      the fluorescence detection system is sensitive enough even for localizing single
      molecules. In this paper, we applied the system as a precise intracellular
      injector (nanoplanter). Fluorescent beads were first chemically immobilized onto
      a ZnO whisker that was glued to an AFM tip and were injected into a living
      BALB/3T3 cell together with the whisker. It was demonstrated that the system
      could clearly show the result of injection, that is, the presence of a small
      number of fluorescent beads in the cell.

PMID- 12211479
TI  - Immobilisation of Semliki forest virus for atomic force microscopy.
AB  - Semliki Forest virus (SFV), an alphavirus, is a single-stranded positive-sense
      RNA virus. The RNA genome is surrounded by a protein shell known as the capsid
      which itself is surrounded by a lipid envelope of host cell origin. In this
      study, SFV strain L10 enveloped virus and its capsid were immobilised onto
      silicon wafer supports which had been pre-coated with a monolayer of the relevant
      anti-viral antibody. After drying, the samples were imaged in air, using non
      contact mode atomic force microscopy (AFM). Quantification of the AFM images has
      revealed that both the strain L10 enveloped virus and capsid collapse when
      immobilised in this manner. The capsid undergoes more significant collapse
      compared to the enveloped virus. The dimensions of the immobilised enveloped
      virus and capsid have been compared to a model where the free spherical particles
      collapse into ellipsoids during immobilisation. For the immobilised capsid the
      dimensions are consistent with this model whereas for the enveloped virus the
      model is less effective. The dimensions of the enveloped virus appear to be
      affected by the antibody used for immobilisation.

PMID- 12211480
TI  - Patterning DNA on microm scale on mica.
AB  - Double-stranded DNA molecules were patterned by selective adsorption to
      aminosilane patterns on mica surfaces. Line patterns with 10 microm spacing were
      made by photolithography and transferred to a polymer stamp. The stamp was then
      used for applying aminosilane molecules by microcontact-printing technique on
      mica substrates. We applied DNA in Tris-EDTA (TE) buffer solution on the
      patterned substrate, and incubated it for 5 min at room temperature. The sample
      was then rinsed with pure water, and dried with nitrogen gas. Tapping mode force
      microscopy showed that DNA was adsorbed selectively on the aminosilanized parts
      of the mica substrate. We also tried to bridge two aluminum electrodes with DNA
      using AC electrophoresis.

PMID- 12211481
TI  - Adsorption kinetics and mechanical properties of thiol-modified DNA-oligos on
      gold investigated by microcantilever sensors.
AB  - Immobilised DNA-oligo layers are scientifically and technologically appealing for
      a wide range of sensor applications such as DNA chips. Using microcantilever
      based sensors with integrated readout, we demonstrate in situ quantitative
      studies of surface-stress formation during self-assembly of a 25-mer thiol
      modified DNA-oligo layer. The self-assembly induces a surface-stress change,
      which closely follows Langmuir adsorption model. The adsorption results in
      compressive surface-stress formation, which might be due to intermolecular
      repulsive forces in the oligo layer. The rate constant of the adsorption depends
      on the concentration of the oligo solution. Based on the calculated rate
      constants a surface free energy of the thiol-modified DNA-oligo adsorption on
      gold is found to be -32.4 kJ mol(-1). The adsorption experiments also indicate
      that first a single layer of DNA-oligos is assembled on the gold surface after
      which a significant unspecific adsorption takes place on top of the first DNA
      oligo layer. The cantilever-based sensor principle has a wide range of
      applications in real-time local monitoring of chemical and biological
      interactions as well as in the detection of specific DNA sequences, proteins and
      particles.

PMID- 12211482
TI  - Mapping of lateral vibration of the tip in atomic force microscopy at the
      torsional resonance of the cantilever.
AB  - Lateral vibration of the tip in atomic force microscopy was mapped at the
      torsional resonance of the cantilever by attaching a shear piezo element at the
      base of the cantilever or under the sample. Fixed frequency excitation and self
      excitation of torsional motion were implemented. The lateral vibration utilized
      as measured by an optical lever was in the order of 10 pm to 3 nm, and its
      frequency approximately 450 kHz for a contact-mode silicon nitride cantilever.
      The amplitude and phase of the torsional motion of the cantilever was measured by
      a lock-in-amplifier or a rectifier and plotted in x and y as the sample was
      raster scanned. The imaging technique gave contrast between graphite terraces,
      self-assembled monolayer domains, silicon and silicon dioxide, graphite and mica.
      Changing contrast was observed as silicon islands oxidized in atmosphere, showing
      that the imaging technique can detect change in lateral tip mobility due to
      changes occurring near the surface. Torsional self-excitation showed nanometric
      features of self-assembled monolayer islands due to different lateral
      dissipation. Dependence of torsional resonance frequency on excitation amplitude,
      and contrast change due to driving frequency around resonance were observed.

PMID- 12211483
TI  - Scanning probe microscopy installed with nanotube probes and nanotube tweezers.
AB  - We have developed well-controlled processes for the growth and manipulation of
      carbon nanotubes. The relatively thin multiwalled nanotubes were prepared with
      high purity by arc discharge with a high gas temperature. In the manipulation of
      nanotubes, the first crucial process is to prepare a nanotube array, so-called
      nanotube cartridge. We have found the alternated current electrophoresis of
      nanotubes by which nanotubes are aligned at the knife-edge of a disposal razor.
      The second important process is to transfer a nanotube from the nanotube
      cartridge onto a substrate in a scanning electron microscope. Using this method,
      we have developed nanotube probes and nanotube tweezers that operate in a
      scanning probe microscope (SPM). The nanotube probes have been applied for
      observation of biological samples and industrial samples to clarify their
      advantages. The nanotube tweezers have been demonstrated for their motion in
      scanning electron microscope and operated to carry a nanomaterial in a SPM.

PMID- 12211484
TI  - Performance of the carbon nano-tube assembled tip for surface shape
      characterization.
AB  - The carbon nano-tube (CNT) has ideal properties for atomic force microscope (AFM)
      tips. We assembled a CNT using 2 three-axial manipulators in a scanning electron
      microscope (SEM) chamber. In this process, the length and angle of the CNT were
      adjusted by observing the SEM image, after which the CNT was glued by
      amorphouscarbon. The results of performance are as follows. The lifetime of the
      CNT tip proved to be 5 times better than that of the silicon tip when
      continuously measuring the micro-roughness of a Czochralski (Cz) P-type (100)
      silicon wafer. The CNT tip is able to trace a narrow space (width less than 1
      microm) better than the conventional silicon tip because of its high aspect
      ratio. The relationship between the observed image and CNT geometry is discussed
      herein.

PMID- 12211485
TI  - Self-sensing piezoresistive cantilever and its magnetic force microscopy
      applications.
AB  - A newly developed Si self-sensing piezoresistive cantilever is presented. Si
      piezoresistive cantilevers for scanning microscopy are fabricated by Si micro
      machining technique. The sensitivity of the piezoresistive cantilever is
      comparable to the current laser detecting system. Topographic images are
      successfully obtained with the piezoresistive cantilever and some comparisons are
      made with the laser detecting system. Furthermore, the magnetic film (Co-Cr-Pt)
      is coated on the tip of the piezoresistive cantilever for magnetic force
      microscopy (MFM) application. The magnetic images are successfully obtained with
      the self-sensing MFM piezoresistive cantilever. The self-sensing piezoresistive
      cantilevers have been successfully applied in scanning probe microscopy and MFM.

PMID- 12211486
TI  - Developments for inverted atomic force microscopy.
AB  - Atomic force microscopy (AFM) has been used to study a wide range of systems.
      Chemically and biologically modified probes have extended AFM by coupling
      chemical and biological information with the physical measurements. In an effort
      to further expand the capabilities of modified AFM probes, previous studies
      investigated the use of an inverted AFM design (i-AFM), wherein a microfabricated
      tip array is used to image a cantilever-supported sample. This report details
      developments in cantilever and tip array fabrication which are aimed at improving
      the applicability and performance of this i-AFM design. Using an epoxy-based
      procedure, commercial cantilevers were modified with a series of standard
      substrates, including template-stripped gold, highly oriented pyrolytic graphite,
      and mica. The samples on these cantilevers were imaged with i-AFM, and lateral
      force images are obtained. This paper demonstrates the first use of i-AFM for
      measuring friction.

PMID- 12211487
TI  - Near-field optical microscopy with video signal processor to apply a CCD imaging
      device as a variable area photo-sensor for improving operability and spectrum
      mode imaging.
AB  - We have developed a video signal processor for improving the operability and
      function of scanning near-field optical microscopy (SNOM). The video signal
      processor applies a CCD imaging device as a variable area photo-sensor in the
      SNOM unit instead of conventional photo-detectors. The signal processor converts
      the intensity of a selected area in video frames to a numerical value with a rate
      of 30 Hz. Consequently, the CCD imaging device can be used as a photo-detector of
      variable areas and positions for detecting a small area of a optical probe
      position. The need for a precise optical axis alignment is relaxed due to the
      large sensing area of the CCD device. Using the video signal processor, near
      field optical and topographic images have been obtained by SNOM/AFM system
      simultaneously. By adding a spectrometer between the SNOM unit and the CCD
      device, the spectrum signal of selected wavelength ranges has been monitored by
      the video signal processor to provide an optical image.

PMID- 12211488
TI  - Mapping and control of atomic force on Si(1 1 1)square root(3) x square root(3)
      Ag surface using noncontact atomic force microscope.
AB  - We demonstrated the possibility of measuring the three-dimensional force-related
      map with true atomic resolution between an Si tip and Si(1 1 1)square root(3) x
      square root(3)-Ag sample surface by measuring the tip-sample distance dependence
      of noncontact atomic force microscope (NC-AFM) image, i.e. atomically resolved
      atomic force spectroscopy. Furthermore, we demonstrated the possibility of
      controlling the interaction force between the atom on the tip apex and a sample
      atom of Si(1 1 1)square root(3) x square root(3)-Ag surface on an atomic scale by
      placing an Ag atom on the Si tip apex instead of Si atom.

PMID- 12211489
TI  - A complementary-metal-oxide-semiconductor-field-effect-transistor-compatible
      atomic force microscopy tip fabrication process and integrated atomic force
      microscopy cantilevers fabricated with this process.
AB  - A complementary-metal-oxide-semiconductor-field-effect-transistor-compatible
      process for the fabrication of atomic force microscopy cantilevers with
      integrated tips has been developed. For the first time, the tips are fabricated
      after the completion of the regular complementary metal-oxide-semiconductor-field
      effect-transistor fabrication process sequence. On-chip circuit components, such
      as piezoresistive deflection sensors, deflection actuators, and amplifiers, are
      fabricated on the mirror-polished surface of the wafer, ensuring optimal
      performance. The tip fabrication process is based on anisotropic silicon etching
      at low temperature using a tetramethylammonium hydroxide solution. The
      anisotropic etching process has been optimized to ensure process controllability.
      Using the described process, complementary-metal-oxide-semiconductor-field-effect
      transistor-based cantilevers with piezoresistive deflection sensors and
      integrated tips have been successfully fabricated. Force-distance curves and
      scanning images in constant-force mode have been recorded.

PMID- 12211490
TI  - Room temperature scanning Hall probe microscopy using GaAs/AlGaAs and Bi micro
      hall probes.
AB  - A room temperature scanning Hall probe microscope system utilizing GaAs/AlGaAs
      and bismuth micro-Hall probes was used for magnetic imaging of ferromagnetic
      domain structures on the surfaces of crystalline thin film garnets and permanent
      magnets. The Bi micro-Hall probes had dimensions ranging between 0.25 and 2.8
      microm2 and were fabricated using a combination of optical lithography and
      focused ion beam milling. The use of bismuth was found to overcome surface
      depletion effects associated with semiconducting micro-Hall probes. Our
      experiments demonstrated that Bi is a practical choice of material for
      fabricating sub-micron sized Hall sensors.

PMID- 12211491
TI  - Effect of locally delivered minocycline microspheres on markers of bone
      resorption.
AB  - BACKGROUND: Gingival crevicular fluid (GCF) biomarkers associated with bone
      resorption may be useful to determine periodontal disease status and response to
      therapy. The pyridinoline cross-linked carboxy-terminal telopeptide of type I
      collagen (ICTP), a bone-specific degradation product, and interleukin 1-beta (IL
      1), a potent bone-resorptive cytokine, have both been associated with periodontal
      disease activity. Minocycline is a tetracycline derivative possessing
      antimicrobial effects on periodontal pathogens and inhibitory properties on
      matrix metalloproteinases (MMPs) associated with tissue destruction. The aim of
      this study was to evaluate the effect of periodontal treatment in the form of
      scaling and root planing (SRP) and locally administered minocycline microspheres
      on the GCF levels of ICTP and IL-1. METHODS: Forty-eight chronic periodontitis
      patients were randomly assigned to 2 groups (SRP plus subgingival application of
      vehicle control [SRP + V], or SRP plus subgingival application of minocycline
      microspheres [SRP + M]) and monitored at 8 sites per subject at baseline and 1,
      3, and 6 months. Four shallow (PD < or = 3 mm) and 4 deep (PD > or = 5 mm) sites
      were evaluated for both marker levels and for probing depth (PD), clinical
      attachment level (CAL), and bleeding on probing (BOP). Eight periodontally
      healthy control subjects with no probing depths >3 mm and no loss of attachment
      were also monitored at the same time intervals. GCF levels of ICTP and IL-1 were
      determined using radioimmunoassay and enzyme-linked immunosorbent assay
      techniques, respectively. RESULTS: Significant differences (P<0.001) in GCF
      levels of ICTP and IL-1 were found between deep and shallow sites at all time
      points in both treatment groups. In addition, healthy subjects demonstrated
      significantly reduced levels of both markers compared to both shallow and deep
      sites in periodontitis patients (P <0.001). Only the SRP + M treated patients
      exhibited significant reductions (P <0.05) in both ICTP and IL-1 levels 1 month
      after treatment. Furthermore, the SRP + M group demonstrated significantly lower
      IL-1 levels (P <0.02) at 1 month compared to the SRP + V group. CONCLUSIONS:
      Results of this study indicate that GCF levels of ICTP and IL-1 correlate with
      clinical measures of periodontal disease and may aid in assessing disease status
      and response to periodontal therapy. Furthermore, local administration of
      minocycline microspheres led to a potent short-term reduction in GCF IL-1 levels.
      Additional studies are needed to address whether repeated administration of
      scaling and root planing along with minocycline microspheres will achieve long
      term reductions in GCF ICTP and IL-1 levels.

PMID- 12211492
TI  - Permeability of Streptococcus mutans and Actinobacillus actinomycetemcomitans
      Through guided tissue regeneration membranes and their effects on attachment of
      periodontal ligament cells.
AB  - BACKGROUND: Microbial colonization on barrier materials used in guided tissue
      regeneration (GTR) may adversely affect treatment outcomes. The purposes of this
      study were: 1) to compare the invasion of Streptococcus mutans and Actinobacillus
      actinomycetemcomitans through 3 GTR membranes, composed of expanded
      polytetrafluoroethylene (ePTFE; non-resorbable), a glycolide fiber composite, and
      type I collagen (both bioabsorbable), and 2) to explore the effects of bacteria
      on the attachment of periodontal ligament (PDL) fibroblasts onto these membranes.
      METHODS: Bacterial permeability was analyzed using a tube capped with a GTR
      membrane as a septum and filled with media. The tube was then placed in a bigger
      tube inoculated with S. mutans or A. actinomycetemcomitans. The passage of
      bacteria through the membranes into the inner tube was monitored. For cellular
      attachment experiments, primary human PDL cells were placed onto the GTR
      membranes with or without bacteria. Attached cells were analyzed by scanning
      electron microscopy (SEM) analysis. RESULTS: The ePTFE membrane had the best
      barrier effects followed by the collagen membrane and then the glycolide fiber
      composite membrane. Moreover, S. mutans passed through these membranes faster
      than A. actinomycetemcomitans. The attachment of PDL cells on the 3 membranes was
      also varied. The ePTFE membrane was the worst substrate for PDL fibroblast
      attachment. Moreover, both bacteria influenced the cellular attachment on the GTR
      membranes. CONCLUSIONS: Differences in the behavior of 3 GTR membranes penetrated
      by S. mutans and A. actinomycetemcomitans were demonstrated. The results suggest
      that attachment of PDL cells was affected on bacterial-contaminated GTR
      membranes, which may alter healing following membrane exposure.

PMID- 12211493
TI  - A study of the initial attachment and subsequent behavior of rat oral epithelial
      cells cultured on titanium.
AB  - BACKGROUND: The seal between an implant and the oral epithelium is an important
      factor for successful implant therapy. The purpose of this study was to evaluate
      the initial attachment and subsequent behavior of rat oral epithelial (OE) cells
      on pure titanium (Ti) used for dental implants. METHODS: OE cells derived from 4
      day-old rats were cultured on Ti, polystyrene culture dishes, and glass
      coverslips. The number of attached cells, cell areas, number of colonies, and
      proliferation rates were measured. Additionally, immunostaining of vinculin and
      laminin-5 (LN5) was performed, and LN5-immunoreactive areas were measured.
      RESULTS: After 24 hours of culture, there were fewer cells attached to the Ti
      than to the polystyrene dishes or glass coverslips, and the area of cells was
      greater on the polystyrene than on the Ti or glass. OE cells reached their
      maximum proliferation rate after 48 hours of culture on the polystyrene and
      glass, and after 72 hours on Ti. LN5 was deposited behind cells as they migrated,
      and the LN5-immunoreactive area was smaller on Ti than on polystyrene after 96
      hours of culture. CONCLUSIONS: The initial attachment of OE cells to Ti was
      inferior to that on polystyrene or glass, and the OE cell migration area
      indicated by the deposition of LN5 was smaller on Ti than on the other materials.
      Therefore, this study suggests that further improvement of Ti surface properties
      is needed for rapid attachment and spreading of oral epithelium to dental
      implants.

PMID- 12211494
TI  - Nifedipine induces gingival epithelial hyperplasia in rats through inhibition of
      apoptosis.
AB  - BACKGROUND: Nifedipine is used as a long-acting vasodilator; one of its side
      effects is gingival overgrowth, characterized by an accumulation of collagenous
      components within the gingival connective tissue and epithelial hyperplasia with
      elongated, branched rete pegs penetrating into the connective tissue. We
      investigated the effect of nifedipine on apoptosis of gingival keratinocytes of
      rats to elucidate the mechanism of nifedipine-induced gingival epithelial
      hyperplasia. METHODS: Twenty-day-old rats were fed a powdered diet containing or
      lacking nifedipine for 8 to 30 days. The mandibular gingiva and palatal mucosa
      were removed on days 8, 15, or 30, and epithelial thickness was examined by light
      microscopy. In situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin
      nick end labeling (TUNEL) assay was used to examine apoptosis of keratinocytes in
      the epithelium. In addition, we examined the effects of nifedipine on
      proliferation of keratinocytes and epithelial cell life on day 8 by 5-bromo-2'
      deoxyuridine (BrdU) staining. RESULTS: Microscopic examination showed gingival
      epithelial hyperplasia in nifedipine-treated rats after day 15. Apoptosis of
      gingival keratinocytes was seen to be inhibited in nifedipine-treated rats on day
      8 and 15. Also, nifedipine did not induce an increase of keratinocyte
      proliferation activity in terms of the number of cells showing positive staining
      with BrdU. Prolongation of cell life by nifedipine was observed on day 8 in
      gingival epithelium through a delay of upward cell movement compared to controls.
      However, epithelial hyperplasia was not detected in palatal mucosa, and there
      were no significant differences in apoptotic rates of keratinocytes and cell life
      between nifedipine-treated rats and control rats. CONCLUSIONS: These results
      suggest that nifedipine induces epithelial hyperplasia in gingival overgrowth not
      by an increase in keratinocyte proliferation, but by prolongation of cell life
      through reduction of apoptosis before epithelial hyperplasia is detectable.

PMID- 12211495
TI  - Detection of Porphyromonas gingivalis DNA in aortic tissue by PCR.
AB  - BACKGROUND: Periodontopathogens may play a role in the etiology of cardiovascular
      disease. The aim of the present study was to investigate biopsies of aortic
      tissue for the presence of periodontopathogens. METHODS: Samples taken from the
      aortas of 26 patients connected to a heart-lung machine during open-heart surgery
      were analyzed in a gene-diagnostics laboratory by polymerase chain reaction.
      Immediately after biopsy, the samples were transferred into liquid nitrogen and
      stored at -80 degrees C. 16S rRNA gene-directed primers were used for general
      detection of bacterial cells, and specific primers for detection of Porphyromonas
      gingivalis and Actinobacillus actinomycetemcomitans. Questionable amplificons
      were verified by Southern hybridization using DNA probes. RESULTS: Bacterial DNA
      was found in 23 of 26 (88.5%) samples, in most cases only in concentrations
      around the detection limit. Four samples were clearly positive for P. gingivalis;
      A. actinomycetemcomitans was not detected. CONCLUSION: These results might
      indicate a link between periodontopathogens entering the cardiovascular system
      and cardiovascular disease.

PMID- 12211496
TI  - The effect of aspirin on the periodontal parameter bleeding on probing.
AB  - BACKGROUND: The absence or presence of bleeding on probing (BOP) is a sign of
      periodontal health or disease, but the presence of BOP is not an accurate
      predictor of disease progression. Aspirin is increasingly used in the prevention
      of cerebrovascular and cardiovascular diseases and is a non-disease factor that
      may modify bleeding indices given its antithrombolytic activity. The purpose of
      this double-blind placebo-controlled randomized clinical trial was to study the
      effect of short-term daily aspirin ingestion on the clinical parameter BOP.
      METHODS: A total of 46 periodontally healthy subjects were included in this
      study: 16 received placebo, 15 low-dose aspirin (81 mg), and 15 regular dose (325
      mg) aspirin. Clinical parameters assessed included plaque index, periodontal
      probing depth, and BOP using an automated pressure-sensitive probe. Measurements
      were recorded before and after 7-day exposure to placebo and aspirin regimens.
      RESULTS: A statistically significant difference in BOP was found in patients with
      > or = 20% of bleeding sites during the visit prior to placebo or aspirin
      exposure (n = 11). The group treated with 325 mg aspirin exhibited a moderate yet
      statistically significant increase in BOP (12.4%) compared to the placebo group
      (there was no significant difference between the 81 mg aspirin group and
      placebo). The tendency to bleed was not statistically significant in the group
      which exhibited <20% (n = 35) of bleeding sites during the visit prior to
      exposure. CONCLUSION: Aspirin intake of 325 mg daily for 7 days moderately
      increased the appearance of bleeding on probing in a population that had > or =
      20% BOP sites.

PMID- 12211497
TI  - Frequency of reactivity for Porphyromonas gingivalis and Prevotella spp. in supra
      and subgingival plaques, and periodontal clinical parameters according to
      subject age.
AB  - BACKGROUND: The present study was conducted to assess the association between
      selected clinical parameters and the distribution of Porphyromonas gingivalis
      (Pg), Prevotella intermedia (Pi), Prevotella nigrescens (Pn), and Prevotella
      melaninogenica (Pm) in supra- and subgingival plaque samples measured by an
      immunoslot blot assay (IBA) using their monoclonal antibodies. METHODS: Plaque
      samples from 299 patients aged 6 to 69 randomly chosen from a group of dental
      outpatients were examined. Plaque index, gingival index, and probing depths were
      evaluated according to the criteria of positive (cell number > or = 10(6)) or
      negative (<106) reactivity to the 4 different monoclonal antibodies. RESULTS: An
      increase in probing depth in subjects exhibiting either a positive or negative
      reaction for the 4 test bacteria was associated with increasing age. Comparing
      bacteria-positive subgingival plaque samples to their corresponding bacteria
      negative counterparts, we found an increased plaque index in children positive
      for any of the 4 bacteria; in addition, that for Pg and Pi was increased in
      subjects 40 to 49 years old. The gingival index increased with increasing amount
      of Pi and Pn, but not with Pg and Pm in those 20 to 29 years of age. The
      frequency of Pg reactivity in subgingival plaque was markedly enhanced in
      subjects older than 30 to 39 years of age, and was significantly higher than that
      in supragingival plaque. The frequency of Pi and Pn reactivity was significantly
      increased in adults aged 20 to 29 and plateaued at older ages. The frequency of
      Pm reactivity was relatively low and independent of subject age. CONCLUSIONS: The
      increase in probing depth with increasing age was not affected by the occurrence
      of periodontopathic bacteria. The high rate of occurrence of Pg, together with Pi
      and Pn, in subgingival plaque of the adult age groups was suggested to be
      associated with the high frequency of periodontal disease in the older age groups
      (above 30 to 49 years of age). The IBA appears to be useful for the efficient and
      rapid detection of periodontopathic bacteria.

PMID- 12211498
TI  - Eikenella corrodens in subgingival plaque: relationship to age and periodontal
      condition.
AB  - BACKGROUND: The purpose of this study was to determine the prevalence and
      distribution of Eikenella corrodens (E. corrodens) in subgingival plaque in
      different age and periodontitis groups and to examine whether its presence is
      related to periodontal diseases. METHODS: A total of 273 subgingival plaque
      samples from 213 periodontitis patients and 60 healthy subjects were assessed.
      Smears from each plaque sample were made and E. corrodens was detected by means
      of indirect immunofluorescent technique. Mean percentage of E. corrodens per
      total bacteria (distribution) was calculated in each sample. The prevalence (% of
      positive samples) and distribution of E. corrodens were statistically analyzed
      based on age or diagnosis by means of Fisher's exact test and analysis of
      variance (ANOVA). RESULTS: Prevalence of E. corrodens decreased by age in the
      healthy control group; however, prevalence did not change in periodontitis
      groups. Distribution of E. corrodens was highest in juvenile periodontitis (JP)
      (2.3 +/- 1.5%) followed by post-JP (1.7 +/- 2.1%), prepubertal periodontitis (1.4
      +/- 1.1%), rapidly progressive periodontitis (0.8 +/- 0.7%), adult periodontitis
      (0.7 +/- 0.6%), and healthy subjects (0.3 +/- 0.3%) (ANOVA, P<0.0001). The <20
      year-old age group with periodontitis showed the highest distribution of E.
      corrodens (2.2 +/- 1.6%) compared to the older age groups who were either healthy
      or had periodontitis (ANOVA, P<0.0001). CONCLUSIONS: Since the distribution of E.
      corrodens is significantly higher in JP, post-JP, and PP, E. corrodens might play
      an important role in the occurrence or progression of periodontitis in young
      patients.

PMID- 12211499
TI  - Immunohistochemical analysis of lymphocyte subpopulations in cyclosporin A
      induced gingival overgrowth.
AB  - BACKGROUND: Cyclosporin A (CsA) is an immunosuppressive agent that is known to
      induce gingival overgrowth (GO). Pharmacological, genetic, immunologic, and
      inflammatory factors seem to be involved in the complex pathogenesis of drug
      induced GO. Lymphocyte subpopulations in human gingival connective tissue have
      been implicated in the pathogenesis of inflammatory periodontal diseases. One
      purpose of this study was to quantify CD4, CD8-, CD57-, and epithelial membrane
      antigen (EMA)-positive cells in the gingiva of renal transplant recipients
      treated with CsA, and compare them to findings in healthy controls. A second aim
      was to correlate cell numbers with clinical findings. METHODS: The study included
      19 kidney recipients who were taking CsA and had significant GO (CsAGO+), 13
      recipients who were taking CsA but showed no GO (CsAGO-), and 14 systemically
      healthy individuals with gingivitis (C). Sections from gingival biopsies were
      incubated with monoclonal antibodies for CD4, CD8, EMA, and CD57, and then
      analyzed using the avidin-biotin complex method. In each specimen, the
      mononuclear cell types were quantified and their distribution was evaluated in 3
      separate tissue zones: S = subepithelial connective tissue beneath the sulcular
      epithelium; O = subepithelial connective tissue beneath the oral epithelium; and
      M = middle connective tissue. RESULTS: There were no significant differences
      among the groups with respect to the numbers of CD4+ and CD8+ cells in each of
      the 3 zones (P >0.05). In zone S, the CsAGO+ group had significantly more EMA
      positive cells than either the C or CsAGO- groups (P <0.05). There were
      significant differences among the groups regarding numbers of CD57+ (natural
      killer) cells in zone M, with the lowest cell numbers in the CsAGO+ patients
      (P<0.05). CONCLUSIONS: The results showed that low numbers of natural killer
      cells are important in the expression of plaque-induced inflammatory changes in
      CsA-associated GO. It appears that these cells may influence the drug's ability
      to induce proliferative activity.

PMID- 12211501
TI  - Calculation of simplified single-root surface area from simulated X-ray
      projection.
AB  - BACKGROUND: The prognosis of a tooth affected by periodontitis might depend on
      the amount of bone remaining around the root surface. The surface area of a
      single tooth root relates to a simulated x-ray projection. METHODS: The aim of
      the study was to determine root surface area from radiographs. Two methods were
      used. In the first, cross-sections of a single-tooth root were simulated using
      ellipses with different eccentricities. Projection data from 90 directions at 1
      degrees intervals were obtained, which were then used to estimate circumferences
      that were then compared with the known circumference. In the second model,
      circumference was estimated from projection data derived from the projection of
      an ellipse with the central ray parallel to the long axis. The estimated
      circumference was compared with possible circumferences resulting from this
      projection data. RESULTS: In the first model, all estimated circumferences are
      less than the true circumferences. The largest error in each case decreased
      rapidly as the eccentricity of the simulated ellipse decreased. Less than 6% of
      the largest errors were found when the eccentricity is 0.83. In the second model,
      the estimation should be within less than 2% of error when the asymmetry factor
      is less than 0.6. CONCLUSIONS: The circumference of an elliptical object can be
      approximated from the projection data of this ellipse. Therefore, the surface
      area of a single tooth root may be estimated with clinically useful accuracy from
      the projection data.

PMID- 12211500
TI  - Evaluation of the titanium Ti-6Al-7Nb alloy with and without plasma-sprayed
      hydroxyapatite coating on growth and viability of cultured osteoblast-like cells.
AB  - BACKGROUND: Osseointegrated dental implants are currently recognized as a
      standard treatment method in dentistry. Titanium (Ti) and its alloys are the
      metals of choice for endosseous parts of currently available dental implants. Ti
      6Al-4V is the most used Ti alloy, however; an improved version, Ti-6Al-7Nb, has
      been recently developed. METHODS: Rat osteoblast-like cells (osteo- 1 culture)
      were used to analyze the biocompatibility of Ti-6Al-7Nb alloy with and without
      hydroxyapatite (HA) coating. The cells were grown on culture Petri dishes on the
      top of either plain Ti-6Al-7Nb or HA-coated Ti-6Al-7Nb disks. Osteo-1 cells grown
      on plain culture dishes were used as controls. Growth and cell viability curves
      were obtained by scanning electron microscopy. For the growth and viability
      curves, 10(4) cells were seeded on 35 mm dishes. Cells from each group were
      counted, in triplicate at 3, 7, 11, and 15 days after seeding using the Trypan
      blue dye exclusion assay. RESULTS: The cells grew as multiple layers on both Ti
      6Al-7Nb substrates, showing extracellular matrix only when grown on HA-coated Ti
      6Al-7Nb disks. The cells grown on HA-coated Ti-6Al-7Nb grew more slowly than the
      other 2 groups, with significantly smaller cell numbers than control cultures at
      the end of the experimental time. Additionally, the HA coated Ti-6Al-7Nb group
      presented smaller percentage of cell viability when compared to the control
      group. However, no significant differences were observed between the Ti groups.
      CONCLUSIONS: The presence of HA on the Ti-6Al-7Nb surface impaired the cell
      growth and viability of osteo-1 cells. However, this coating improved the
      extracellular matrix formation. Thus, our cell viability and structural studies
      showed that Ti-6Al-7Nb with or without HA coating has relevant physical and
      biological properties as an implant material.

PMID- 12211502
TI  - Periodontal therapy may reduce the risk of preterm low birth weight in women with
      periodontal disease: a randomized controlled trial.
AB  - BACKGROUND: Recent studies have suggested that periodontal disease is a risk
      factor for preterm low birth weight (PLBW). A randomized controlled trial was
      undertaken to help further evaluate the proposed association between periodontal
      disease and PLBW. METHODS: Four hundred pregnant women with periodontal disease,
      aged 18 to 35, were enrolled while receiving prenatal care in Santiago, Chile.
      Women were randomly assigned to either an experimental group (n = 200), which
      received periodontal treatment before 28 weeks of gestation or to a control group
      (n = 200) which received periodontal treatment after delivery. Previous and
      current pregnancies and known risk factors were obtained from patient medical
      records and interviews. The primary outcome assessed was the delivery at less
      than 37 weeks of gestation or an infant weighing less than 2,500 g. RESULTS: Of
      the 400 women enrolled, 49 were excluded from the analyses for different reasons.
      The incidence of PLBW in the treatment group was 1.84% (3/163) and in the control
      group was 10.11% (19/188), (odds ratio [OR] 5.49, 95% confidence interval [CI]
      1.65 to 18.22, P= 0.001). Multivariate logistic regression analysis showed that
      periodontal disease was the strongest factor related to PLBW (OR 4.70, 95% CI
      1.29 to 17.13). Other factors significantly associated with such deliveries were:
      previous PLBW (OR 3.98, 95% CI 1.11 to 14.21), less than 6 prenatal visits (OR
      3.70, 95% Cl 1.46 to 9.38), and maternal low weight gain (OR 3.42, 95% CI 1.16 to
      10.03). CONCLUSIONS: Periodontal disease appears to be an independent risk factor
      for PLBW. Periodontal therapy significantly reduces the rates of PLBW in this
      population of women with periodontal disease.

PMID- 12211503
TI  - Factors that modulate the effects of bone morphogenetic protein-induced
      periodontal regeneration: a critical review.
AB  - The healing process initiated by a single molecular species of bone morphogenetic
      protein (BMP) such as BMP-2 or BMP-7 sets in motion a cascade of cellular events
      resulting in differentiation of progenitor cells into phenotypes involved in
      periodontal regeneration. For example, animal studies show that a single dose of
      recombinant human (rh) BMP-2 increases the rate of normal intramembranous bone
      formation and enhanced cementum formation during periodontal wound healing.
      However, the optimal effects of BMPs are modulated by a range of factors that
      need careful evaluation in clinical studies. These factors include the influence
      of root conditioning, occlusal loading, BMP dose, and the release characteristics
      of the carrier as well as the suitability of the model to evaluate the efficacy
      of BMPs. Each of these factors may affect the rate of BMP-induced osteogenesis
      and cementogenesis and subsequent periodontal ligament (PDL) formation during the
      early and late stages of periodontal wound healing. Although BMP-2 initiates stem
      cells along an osteogenic pathway, the dose may have to be of sufficient
      concentration to ensure other growth and differentiation factors do not redirect
      or retard the osteogenic potential of the cell. Understanding when to manipulate
      the cell's differentiation pathway with the application of single or multiple
      doses of BMPs at the appropriate concentration is required to optimize the effect
      of BMPs in periodontal wound healing. Therefore, different release profiles from
      the same carrier may be particularly important in tissues with mixed cell
      populations such as in the periodontium, where similar tissues like bone and
      cementum grow at different rates. Furthermore, treatment of intrabony defects
      with BMPs are likely to not only require appropriate temporal release of the
      BMP(s), but also a carrier that can serve as a template for new tissue formation
      providing space maintenance and supporting the mucoperiosteal flap. Many of these
      issues have not been adequately addressed from a periodontal standpoint;
      therefore the purpose of this review is to clarify our current understanding of
      the factors that are likely to modulate the effects of BMP-induced periodontal
      regeneration. Moreover, assessing the importance of these factors is essential
      prior to conducting expensive human clinical trials.

PMID- 12211504
TI  - Primary extranodal malignant lymphoma affecting the periodontium.
AB  - BACKGROUND: Non-Hodgkin's lymphoma may arise in extranodal tissues within the
      head and neck region. These lesions may occur in the oral cavity, but rarely
      appear on the gingiva. Due to their malignant nature, rapid identification,
      diagnosis, and treatment of non-Hodgkin's lymphomas are essential to patient
      survival. METHODS: An unusual case of primary extranodal non-Hodgkin's lymphoma
      is described. The small lesion arose on the gingiva and alveolar mucosa. Upon
      excision, the tissue was submitted for microscopic examination, with the
      expectation that the lesion would be benign and excision would constitute the
      entirety of treatment. However, a diagnosis of primary extranodal large B-cell
      lymphoma was returned. RESULTS: In addition to excision of the lesion, the
      patient underwent a complete work-up to rule out other systemic lesions.
      Chemotherapy and radiation therapy were performed. The patient has remained
      healthy, without recurrence of lymphoma for 3 years. CONCLUSIONS: This case
      reinforces the importance of submitting excised tissues for microscopic
      examination even when the lesion appears totally benign. In addition, it
      highlights the need for complete excision of suspected lesions, with generous
      borders of normal tissue. With current periodontal plastic surgical techniques,
      most defects remaining after soft tissue biopsy can be managed with good esthetic
      results.

PMID- 12211505
TI  - A retrospective case series comparing the use of demineralized freeze-dried bone
      allograft and freeze-dried bone allograft combined with enamel matrix derivative
      for the treatment of advanced osseous lesions.
AB  - BACKGROUND: Combined regenerative approaches have been used for treating advanced
      osseous lesions around teeth. The aim of combining treatments is to enhance both
      clinical predictability and regenerative outcome compared to a monotherapeutic
      approach. This case series from a private practice reports on the clinical
      efficacy of an enamel matrix derivative (EMD) combined with either demineralized
      freeze-dried bone allograft (DFDBA) or freeze-dried bone allograft (FDBA) in the
      treatment of advanced infrabony lesions. The advanced lesions were veneered by a
      rapidly formed absorbable polymer barrier of poly(DL-lactide) to enhance graft
      containment. METHODS: A total of 22 consecutive patients, each contributing one
      infrabony lesion, are reported. After patients completed presurgical preparation,
      the infrabony lesions were surgically treated with a combined approach that
      included root surface treatment with citric acid. The two groups differed in
      their composite graft; one received DFDBA-EMD (n = 10) and the other received
      FDBA-EMD (n = 12). Patients followed a stringent postoperative protocol and were
      evaluated 6 months postsurgery. Clinical outcomes were assessed by changes in
      clinical attachment level (CAL) and probing depth (PD) from pretreatment.
      Surgical re-entry of several sites was possible in each group. RESULTS: CAL at
      pretreatment measured 9.2 +/- 1.3 mm and 9.1 +/- 1.9 mm for DFDBA-EMD and FDBA
      EMD groups, respectively, with corresponding PD of 8.4 +/- 1.6 mm and 8.9 +/- 2.0
      mm for each group. At 6 months post-treatment, CALs were reduced to 4.7 +/- 1.3
      mm and 3.8 +/- 1.0 mm for DFDBA-EMD and FDBA-EMD groups, respectively; with
      corresponding PD decreased to 3.0 +/- 0.8 mm and 3.2 +/- 1.0 mm. Relative
      improvements in CAL for the DFDBA-EMD and DFDBA-EMD groups were 49.1% +/- 11.0%
      and 57.3% +/- 9.4%, respectively (P <0.07). CONCLUSIONS: This case series
      demonstrates the clinical benefits of using a combined therapeutic approach in
      which a biologic mediator (EMD) was combined with either DFDBA or FDBA. In this
      limited case series, a trend was observed towards greater improvement in clinical
      attachment level gain in advanced infrabony defects when EMD was combined with
      FDBA as compared to DFDBA. Larger prospective controlled clinical trials are
      needed to determine if differences exist in the relative efficacy of DFDBA versus
      FDBA in combination with EMD.

PMID- 12211506
TI  - Periodontal diseases are curable.

PMID- 12211507
TI  - Periodontal management of patients with cardiovascular diseases.
AB  - Periodontists are often called upon to provide periodontal therapy for patients
      with a variety of cardiovascular diseases. Safe and effective periodontal
      treatment requires a general understanding of the underlying cardiovascular
      diseases, their medical management, and necessary modifications to
      dental/periodontal therapy that may be required. In this informational paper more
      common cardiovascular disorders will be discussed and dental management
      considerations briefly described. This paper is intended for the use of
      periodontists and members of the dental profession.

PMID- 12211508
TI  - Obese, older adults with knee osteoarthritis: weight loss, exercise, and quality
      of life.
AB  - This study examined the effects of dietary weight loss and exercise on the health
      related quality of life (HRQL) of overweight and obese, older adults with knee
      osteoarthritis. A total of 316 older men and women with documented evidence of
      knee osteoarthritis were randomly assigned to 1 of 4 18-month interventions:
      dietary weight loss, exercise, dietary weight loss and exercise, or healthy
      lifestyle control. Measures included the SF-36 Health Survey and satisfaction
      with body function and appearance. Results revealed that the combined diet and
      exercise intervention had the most consistent, positive effect on HRQL compared
      with the control group; however, findings were restricted to measures of physical
      health or psychological outcomes that are related to the physical self.

PMID- 12211509
TI  - Effects of a videotape information intervention for spouses on spouse distress
      and patient recovery from surgery.
AB  - Shortly before hospital release, the spouses of 226 male and 70 female coronary
      artery bypass graft patients were randomly assigned to view an optimistically
      slanted information tape, a tape that featured coping with more ups and downs, or
      no tape at all. Results indicated that women, whether as patients or as
      caregivers, were at elevated risk for a variety of negative outcomes during the
      subsequent 6 months. However, female patients who had spouses in the optimistic,
      mastery-tape condition were protected from the elevated levels of problems that
      characterized women whose spouses received only standard discharge preparation.
      Results are discussed in relation to research on optimism effects and work that
      suggests men may generally be less effective caregivers than women.

PMID- 12211510
TI  - Long-term psychological sequelae of smoking cessation and relapse.
AB  - The authors examined whether smoking cessation and relapse were associated with
      changes in stress, negative affect, and smoking-related beliefs. Quitters showed
      decreasing stress, increasing negative health beliefs about smoking, and
      decreasing beliefs in smoking's psychological benefits. Quitters became
      indistinguishable from stable nonsmokers in stress and personalized health
      beliefs, but quitters maintained stronger beliefs in the psychological benefits
      of smoking than stable nonsmokers. Relapse was not associated with increases in
      stress or negative affect However, relapsers increased their positive beliefs
      about smoking and became indistinguishable from smokers in their beliefs. For
      quitters, decreased stress and negative beliefs about smoking may help maintain
      successful cessation. However, for relapsers, declining health risk perceptions
      may undermine future quit attempts.

PMID- 12211511
TI  - Motivational interviewing in health promotion: it sounds like something is
      changing.
AB  - Motivational interviewing (MI), initially developed for addiction counseling, has
      increasingly been applied in public health, medical, and health promotion
      settings. This article provides an overview of MI, outlining its philosophic
      orientation and essential strategies. Major outcome studies are reviewed, nuances
      associated with the use of MI in health promotion and chronic disease prevention
      are described, and future directions are offered.

PMID- 12211512
TI  - Adherence to exercise prescriptions: effects of prescribing moderate versus
      higher levels of intensity and frequency.
AB  - Sedentary adults (N = 379) were randomly assigned in a 2 x 2 design to walk 30
      min per day at a frequency of either 3-4 or 5-7 days per week, at an intensity of
      either 45%-55% or 65%-75% of maximum heart rate reserve. Analyses of exercise
      accumulated over 6 months showed greater amounts completed in the higher
      frequency (p = .0001) and moderate intensity (p = .021) conditions. Analyses of
      percentage of prescribed exercise completed showed greater adherence in the
      moderate intensity(p = .02) condition. Prescribing a higher frequency increased
      the accumulation of exercise without a decline in adherence, whereas prescribing
      a higher intensity decreased adherence and resulted in the completion of less
      exercise.

PMID- 12211513
TI  - Examining social-cognitive determinants of intention and physical activity among
      black and white adolescent girls using structural equation modeling.
AB  - Structural equation modeling was used to evaluate components within the theories
      of reasoned action (TRA), planned behavior (TPB), and self-efficacy (SET) for
      understanding moderate and vigorous physical activity among 1,797 Black and White
      adolescent girls. Modest to strong support was provided for components of TPB and
      SET; weak support was provided for components of TRA. Perceived behavioral
      control was related to vigorous physical activity. Self-efficacy was related to
      moderate and vigorous physical activity, and it accounted for the effect of
      intention on physical activity. The observed relationships were similar between
      Black and White girls. Self-efficacy and perceived behavioral control are
      independent influences on physical activity among Black and White adolescent
      girls and warrant study as potential mediators in physical activity
      interventions.

PMID- 12211514
TI  - Effect of family environment and donor source on patient quality of life
      following renal transplantation.
AB  - The authors examined the degree to which the supportiveness of a patient's family
      environment predicts change in quality of life following renal transplantation.
      The sample consisted of 95 patients receiving renal grafts from either a living
      donor or a cadaveric donor. Patients were initially assessed prior to
      transplantation with follow-up assessment occurring an average of 5.5 months
      after transplantation. Among patients receiving a living-donor kidney, those
      reporting a more supportive family environment exhibited reduced depression,
      improved mobility, and improved social functioning. However, those living-donor
      recipients reporting less family support exhibited increased depression and
      diminished mobility and social functioning after transplantation. Patients
      receiving a kidney from a cadaveric donor showed modest improvements in quality
      of life regardless of the degree of family support.

PMID- 12211515
TI  - Beyond invulnerability: the importance of benefits in adolescents' decision to
      drink alcohol.
AB  - Some investigators propose that adolescents engage in risky behaviors mainly
      because they perceive themselves to be invulnerable to risk. However, studies
      have typically not included perceived benefits. In the current study, 5th, 7th,
      and 9th graders were surveyed about their perceptions of and experience with
      alcohol and tobacco. Results indicated that perceptions of the benefits were
      significantly related to drinking and smoking 6 months later, over and above
      perceptions of the risks, age of the respondent, and experience level. Further,
      the importance of benefits was replicated across 3 separate analyses. Experience
      with alcohol alone, especially positive experience, was also related to
      perception and behavior. These findings are discussed in terms of how to improve
      messages and influence adolescents' decisions regarding risk-taking behaviors.

PMID- 12211516
TI  - Psychological impact of benign breast biopsy: a longitudinal, comparative study.
AB  - The impact of benign breast biopsy (BBB) on distress and perceptions of risk for
      breast cancer (BC) was examined. Interviews were conducted with 100 women shortly
      after notification of biopsy results and 4 and 8 months post-BBB. Compared with
      matched healthy comparison (HC) women without BBB, the BBB group evidenced
      greater BC-specific distress at baseline. BC-specific distress declined after
      BBB, remaining elevated relative to the HC group at the 8-month follow-up.
      Dispositional (optimism, informational coping style), demographic (education),
      clinical (family history of BC), and cognitive (BC risk perception) variables
      were associated with baseline levels of BC-specific distress or persistence of
      distress. Results support the monitoring process model (S. M. Miller, 1995) and
      the cognitive social health information processing model (S. M. Miller, Y. Shoda,
      & K. Hurley, 1996).

PMID- 12211517
TI  - Pathways through adolescent smoking: a 7-year longitudinal grouping analysis.
AB  - This study examined longitudinal patterns of smoking among students (N = 852)
      followed from 6th through 12th grades using longitudinal grouping analysis. Six
      patterns (clusters) were identified: nonsmokers, quitters, experimenters, early
      escalators, late escalators, and continuous smokers. Baseline (6th-grade)
      differences in associated risk factors were examined. Growth curve modeling
      revealed meaningful intercluster differences in risk factor trends over the study
      period. In general, nonsmokers had the fewest baseline risk factors and slowest
      increase in risk factors, whereas continuous smokers had higher baseline and more
      rapidly increasing trends in risk factors. Results suggest that some clusters may
      respond to population-based antismoking interventions, whereas others (early
      escalators and continuous smokers) will probably require more focused
      interventions.

PMID- 12211518
TI  - Comparison of price change and health message interventions in promoting healthy
      food choices.
AB  - This study examines the feasibility and effectiveness of an environmental
      intervention for improving diet by comparing the impact of health messages,
      lowered prices, and their combination on the purchase of healthy food items in a
      restaurant. Price decreases alone, rather than a combination of price decreases
      and health messages, were associated with a higher level of increased purchases
      of some healthy food items as compared with control items over a 4-month period.
      Price decreases may be a more powerful means than health messages of increasing
      consumption of healthy foods. Health messages may have paradoxical effects if
      foods labeled as healthy are assumed to taste bad.

PMID- 12211519
TI  - Predicting future blood donor returns: past behavior, intentions, and observer
      effects.
AB  - A prospective design was used to explore the efficacy of 6 factors (e.g.,
      intentions) to predict the number of future blood donations in an initial sample
      of 630 blood donors. Differential predictions are made for the roles of past
      behavior and intentions with respect to occasional (4 or fewer previous blood
      donations) and regular (5 or more previous blood donations) blood donors.
      Intentions were predictive for occasional donors, and past behavior was
      predictive for regular donors. Furthermore, for regular donors only, an inverted
      U-shaped curve explained the relationship between past behavior and future
      behavior. Finally, it is reported that observing others fainting produces a
      reduction in the number of future donations for occasional donors. The
      theoretical and practical implications of these findings are discussed.

PMID- 12211520
TI  - Mind over matter: internalization of the thinness norm as a moderator of
      responsiveness to norm misperception education in college women.
AB  - The authors examine the effectiveness of norm misperception education in
      decreasing disordered eating. One hundred seven 1st-year college women completed
      questionnaires assessing their own and others' actual and ideal body size as well
      as their own disordered eating and were then randomly assigned to read either a
      norm misperception or a control brochure. Participants completed questionnaires
      immediately after reading the brochures and again 3 months later. Although there
      were no main effects of brochure condition at the follow-up, participants who
      primarily compared themselves with other college women and who read the norm
      misperception brochure had higher actual and ideal weight as well as less
      frequent disordered eating. The discussion focuses on the theoretical and applied
      implications of these findings.

PMID- 12211521
TI  - Sumatriptan-induced chest symptoms in Japanese.

PMID- 12211522
TI  - Beta-blockers have beneficial effects even on unclassified cardiomyopathy such as
      isolated ventricular noncompaction.

PMID- 12211523
TI  - Epstein-Barr virus survival: expression and release of Fas ligand.

PMID- 12211524
TI  - Polymyalgia rheumatica and elderly-onset rheumatoid arthritis.

PMID- 12211525
TI  - Upper respiratory tract tuberculosis; rare but clinically important infectious
      disease.

PMID- 12211526
TI  - High-dose immunoablative therapy with hematopoietic stem cell support in the
      treatment of severe autoimmune disease: current status and future direction.
AB  - In the past 5 years approximately 500 patients worldwide suffering from severe
      autoimmune disease (AD) have received an autologous hematopoietic stem cell
      transplantation (HSCT) as treatment following high-dose chemotherapy. The EBMT
      and EULAR data base contains 370 registrations, the most frequently transplanted
      ADs being multiple sclerosis (MS), systemic sclerosis (SSc), rheumatoid arthritis
      (RA), juvenile idiopathic arthritis (JIA), systemic lupus erythematosus (SLE) and
      idiopathic thrombocytopenic purpura (ITP). Around 70% responded initially well,
      with durable remission/stabilization seen more frequently in MS and SSc than in
      RA and SLE, the latter having around 2/3 relapses, the majority of which respond
      to simple agents. Overall 8% transplant-related mortality was seen with large
      inter AD differences (12.5% in SSc and only one patient in RA) probably
      reflecting the degree of vital organ involvement at the time of transplant. This
      phase I/II data has led to a running phase III randomized trial in SSc called the
      Autologous Stem cell Transplantation International Scleroderma (ASTIS) trial, and
      it will soon begin in MS (ASTIMS) and RA (ASTIRA). The concept of immunological
      "re-setting" has evolved, and needs to be confirmed by longer follow-up and the
      multicentre, international phase III randomized studies.

PMID- 12211527
TI  - High mortality in hospitalized elderly patients with feeding tube placement.
AB  - OBJECTIVE: We investigated the influence of feeding tube placement on survival in
      hospitalized elderly patients. METHODS: To assess long-term mortality in an
      inception cohort and the influence of feeding tube placement on survival, one
      hundred six hospitalized elderly patients from a nursing home were followed up
      through and after the index hospitalization for placement of a feeding tube and
      mortality. Cox regression hazards model was constructed for both univariate and
      multivariate analyses. RESULTS: A feeding tube was placed in 15% (16/106) of the
      study patients during the index hospitalization. Median survival of the 106
      patients was 381 days. A total of 92 patients (87%) survived the index
      hospitalization, and 52 (49%) were still alive at the last follow-up. In the
      multivariate survival model which included older age, hip fracture history,
      admitting diagnosis of pneumonia, and tube feeding placement, only feeding tube
      placement (hazard ratio, 2.29; 95% confidence interval, 1.22-4.33) was
      significantly associated with higher mortality. CONCLUSION: In hospitalized
      elderly patients from nursing home, feeding tube placement may be a risk factor
      for mortality.

PMID- 12211528
TI  - Pathological analysis of the cavitary wall in Mycobacterium avium intracellulare
      complex pulmonary infection.
AB  - OBJECTIVE: The present study was designed to evaluate the process of cavity
      formation in Mycobacterium avium intracellulare complex (MAC) lung infection,
      pathologically and clinically. METHODS: Using resected lung specimens, we first
      evaluated the distribution of MAC as well as the distribution of myofibroblasts
      in MAC lung infection according to several pathological findings classified as
      bronchiectasis, centrilobular nodules, cavity, nodules, bronchiolitis, or
      consolidation. Resected lung specimens (9 cases) were evaluated by special
      staining: Ziehl-Neelsen's method and immunohistochemically for CD68 (stain for
      monocytes and macrophages) and alpha-smooth muscle actin (stain for
      myofibroblasts). Chest CT findings were also examined in these 9 patients. In
      addition, the serial chest CT scans were reviewed in another 3 patients to
      evaluate the process of cavity formation, radiologically. RESULTS: Although
      extensive granuloma formations were observed in every pathological
      classification, MAC was demonstrated only in the necrotic tissue of the inner
      surface of the cavitary wall, which was connected to the airway. Myofibroblasts
      which expressed alpha-smooth muscle actin were intensely demonstrated in the
      cavitary wall compared with other pathological classifications. In the cavitary
      wall, the layer of epithelioid cells and multinucleated giant cells surrounded
      necrosis, and the layer of myofibroblasts surrounded the layer of epithelioid
      cells. Chest CT findings demonstrated that the cavitary walls were relatively
      thick. The evaluation of serial chest CT scans demonstrated that cavities were
      formed from previously existing nodules. CONCLUSIONS: Detection of mycobacteria
      in the cavitary wall, massive infiltration of myofibroblasts compared with other
      pathological classifications, and connection to the drainage bronchus, were
      believed to be important in the process of cavity formation in MAC pulmonary
      infection.

PMID- 12211529
TI  - Evidence against strong correlation between chest symptoms and ischemic coronary
      changes after subcutaneous sumatriptan injection.
AB  - OBJECTIVE: To evaluate the adverse events possibly caused by sumatriptan
      injection and explore the relationship between chest symptoms along with
      sumatriptan injection and coronary ischemia among Japanese patients with
      migraine. METHODS: A cumulative total of 112 subcutaneous injections in 62
      patients were evaluated. ECG was continuously monitored before and until 5
      minutes after injection on 92 occasions. PATIENTS: Sixteen men and 46 women aged
      from 16 to 60 (mean 39+/-12) years. Their clinical diagnoses were migraine with
      aura, migraine without aura, cluster headache, and others. RESULTS: Chest
      symptoms occurred following 17% of all injections and in 15% of all patients.
      None of these chest symptoms was accompanied by ECG changes. CONCLUSIONS:
      Although the risk of coronary ischemia with sumatriptan treatment is commonly
      stated, our data suggest that chest symptoms following sumatriptan injection are
      not strongly associated with coronary ischemia in the Japanese population. The
      mechanism of chest symptoms following sumatriptan administration should be
      further elucidated.

PMID- 12211530
TI  - Contribution of research in basic and clinical sciences in Japan.
AB  - OBJECTIVE: To investigate the degree of Japan's contribution in basic and
      clinical research in the last decade. METHODS: Original articles published in
      1990-2000 in highly reputed basic and clinical journals were accessed through
      MEDLINE database. The number of articles having affiliation with a Japanese
      institution was counted separately for basic and clinical journals. RESULTS: Of
      total articles, Japan's contributions in basic and clinical research were 3.1%
      and 0.7%, respectively (p=0.0001). The recent increase in the contribution was
      significant for basic research (p=0.01), but not for clinical research (p=0.91).
      CONCLUSION: The barriers to boosting high quality clinical research in Japan
      should be determined and accordingly appropriate measures should be taken
      forthwith.

PMID- 12211531
TI  - Ulcerative colitis in monozygotic twin sisters.
AB  - We present a rare occurrence of woman monozygotic twins with ulcerative colitis
      (UC). A 21-year-old woman came to our hospital because of diarrhea, abdominal
      pain and hematochezia. We diagnosed this case as proctitis type UC by endoscopic
      and histological findings. Six months later, her twin sister developed total
      colitis type UC. Both twins had HLA-A24, B52, DR2, and DQ1 serological types, and
      had DRB1*1502 DNA type, previously shown to be associated with UC. This case
      report suggested an association of genetic factor together with environmental
      factors in the etiology for UC.

PMID- 12211532
TI  - Inflammatory pseudotumor of the mesentery causing portal venous thrombosis and
      cavernomatous transformation.
AB  - A 32-year-old man was admitted to our hospital complaining of abdominal pain in
      the left upper quadrant. A mass was palpable on the left side of the umbilicus.
      Laboratory data revealed anemia, elevated erythrocyte sedimentation rate,
      hypergammaglobulinemia, and prolonged prothrombin time. Computed tomography
      demonstrated a soft tissue mass in the mesentery of the jejunum, portal venous
      thrombosis, and cavernomatous transformation in the porta hepatis. The patient
      was eventually diagnosed by laparoscopic partial resection as having inflammatory
      pseudotumor of the mesentery. Four months later, all of his symptoms and abnormal
      laboratory findings completely disappeared without any therapy. Inflammatory
      pseudotumor should be kept in mind as a cause of portal venous thrombosis, and/or
      cavernomatous transformation although it is rare.

PMID- 12211533
TI  - Crow-Fukase syndrome associated with high-output heart failure.
AB  - A 64-year-old woman was admitted with systemic edema and exertional dyspnea. High
      output heart failure was diagnosed by right heart catheterization and she was
      treated with diuretics. After 3 weeks, her symptoms disappeared but a high
      cardiac output state persisted. A diagnosis of Crow-Fukase syndrome was made
      based on the presence of polyneuropathy, organomegaly, endocrinopathy, M-protein,
      and skin changes. Her serum vascular endothelial growth factor (VEGF) level was
      markedly elevated after recovery from heart failure. We suspect that an elevated
      VEGF level and a high cardiac output state may play a role in the pathogenesis of
      heart failure in Crow-Fukase syndrome.

PMID- 12211534
TI  - Carvedilol-induced changes in cardiac diastolic performance in a patient with
      isolated noncompaction of the myocardium.
AB  - Isolated ventricular noncompaction (IVNC) is an unusual congenital heart disease.
      The morphological features are trabeculations and intertrabecular recesses within
      the left ventricle. Important clinical considerations include the high mortality
      due to depressed cardiac function, and the instance of ventricular arrhythmia and
      systemic embolism. One of reasons for the high mortality is that there is still
      no effective therapy with the exception of the recommendation for anticoagulation
      therapy to prevent embolisms. Hence, we describe a 29-year-old man with IVNC
      presenting with chronic heart failure. Careful up-titration of carvedilol in this
      patient changed the parameters of cardiac diastolic performance

PMID- 12211535
TI  - Successful salvage therapy of irinotecan for relapsed Hodgkin's lymphoma.
AB  - A 30-year-old man, who had a repeated history of relapsed Hodgkin's lymphoma over
      7 years, developed bilateral pleural effusion and chest wall involvement. He was
      treated with weekly irinotecan hydrochloride (CPT-11; 80 mg/m2/week). Partial
      response was observed after two cycles of irinotecan. Neutropenia and diarrhea
      were tolerable. This case demonstrated that irinotecan has a therapeutic effect
      in patients with relapsed Hodgkin's lymphoma.

PMID- 12211536
TI  - A possible mechanism of NK cell-lineage granular lymphocyte proliferative
      disorder (NK-GLPD) in a patient with chronic active Epstein-Barr virus infection
      (CAEBV) and severe hypersensitivity to mosquito bites (SHMB).
AB  - We report the case of a young female patient with chronic active Epstein-Barr
      virus infection (CAEBV) and severe hypersensitivity to mosquito bites (SHMB). She
      showed a marked increase of NK cell population in peripheral blood. The NK cell
      population was suggested to be infected with EBV, and to be oligoclonal by
      Southern blotting using an EBV genome terminal-repeat probe. The NK cells
      aberrantly expressed CD25, a high affinity receptor for IL-2, and showed an
      augmented in vitro proliferative response to IL-2. Moreover, they also showed
      enhanced expression of both Fas-ligand and Bcl-2, and resistance to in vitro Fas
      induced apoptotic cell death (Fas-ACD). Taken together, these observations
      suggested that both the augmentation of proliferative response to IL-2 and the
      decrease in Fas-ACD may cause NK cell lineage granular lymphocyte proliferative
      disorder (NK-GLPD) in patients with CAEBV and SHMB.

PMID- 12211537
TI  - Elderly onset rheumatoid arthritis complicated by polymyalgia rheumatica.
AB  - We report herein the case of a 70-year-old patient with elderly onset rheumatoid
      arthritis associated with severe muscle pain in shoulder and pelvic girdle. The
      patient revealed erosive polyarthritis with high titers of rheumatoid factor.
      Muscle pain started one month after the onset of rheumatoid arthritis followed by
      muscle weakness and muscle atrophy. Synovial effusion and edema in the soft
      tissue outside of the articular capsule in the knee joint were confirmed
      ultrasonographically. Administration of prednisolone at 20 mg/day dramatically
      abolished the muscular manifestations. The coexistence of an early stage of
      elderly onset rheumatoid arthritis and polymyalgia rheumatica was considered due
      to the presence of seropositive erosive arthritis and severe muscle
      manifestations at the same time.

PMID- 12211538
TI  - Active hepatic capsulitis caused by Paragonimus westermani infection.
AB  - Paragonimiasis is an important re-emerging parasitosis in Japan. Although the
      lungs and pleural cavity are the principal sites affected with the parasite,
      ectopic infection can occur in unexpected sites such as skin and brain. This case
      report describes a patient with active hepatic capsulitis due to Paragonimus
      westermani infection. The patient was successfully treated with praziquantel at
      the dose of 75 mg/kg/day for 3 days.

PMID- 12211539
TI  - Tonsillar tuberculosis associated with pulmonary and laryngeal foci.
AB  - Tonsillar tuberculosis is one of the uncommon forms of extrapulmonary
      tuberculosis. We report a case of tonsillar tuberculosis associated with
      pulmonary and laryngeal foci. A 23-year-old female was admitted for evaluation of
      hoarseness and difficulty in swallowing. Bilateral palatine tonsils were
      enlarged, and a tonsillectomy was performed. Since a histological study revealed
      tonsillar tuberculosis, antituberculous agents were administered. After the
      treatment the pulmonary lesions detected with chest computed tomography were
      improved, and her symptoms were relieved. The possibility of tonsillar
      tuberculosis should be considered when unexplained enlarged tonsil is observed in
      patients with pulmonary tuberculosis.

PMID- 12211540
TI  - Afebrile scrub typhus (Tsutsugamushi disease) with acute respiratory distress
      syndrome.
AB  - A 74-year-old Japanese man with scrub typhus presented without the typical
      symptom of high fever and subsequently developed the complication of acute
      respiratory distress syndrome. It was suspected that exposure occurred at the
      river side of Kinugawa, Tochigi Prefecture, Japan. His body temperature was below
      38.0 degrees C. After intensive supportive care and minocycline therapy, he
      dramatically recovered. With the increase in popularity of outdoor recreation,
      scrub typhus can be found in clinics all over Japan. Physicians should therefore
      be aware of the manifestations of the disease and the necessity of early
      treatment in suspected cases.

PMID- 12211542
TI  - Preference of laparoscopic splenectomy over steroid therapy in a young field
      athlete with immune thrombocytopenic purpura.

PMID- 12211541
TI  - Successful non-surgical treatment of brain abscess and necrotizing fasciitis
      caused by Bacillus cereus.
AB  - Musculoskeletal and central nervous system infections caused by Bacillus cereus
      are very rare. Only a few cases have been reported, whose clinical courses
      strongly suggested that surgical procedures combined with appropriate
      antimicrobial therapy are necessary to cure these infections. A 60-year-old man
      with severe neutropenia due to myelodysplastic syndrome, developing necrotizing
      fasciitis and brain abscess caused by Bacillus cereus is reported. Without
      performing any surgical procedures, the patient was successfully treated with
      systemic antimicrobial therapy combined with granulocyte colony stimulating
      factor, which contributed to the increase in the neutrophil count.

PMID- 12211543
TI  - Chronic advanced pulmonary hypertension.

PMID- 12211544
TI  - X-ray absolute calibration of the time response of a silicon photodiode.
AB  - The time-dependent response of a 1-mm2 silicon photodiode was characterized by
      use of pulsed synchrotron radiation in the 4- to 16-nm-wavelength range. Modeling
      the input radiation pulse and the electrical response of the photodiode allowed
      the photodiode's capacitance as a function of wavelength and applied bias voltage
      to be determined. The capacitance was in the 7- to 19-pF range and resulted in
      response fall times as small as 0.4 ns. The capacitance determined by pulsed x
      ray illumination was in good agreement with the capacitance determined by pulsed
      optical laser illumination. The absolute responsivity was measured by comparison
      with the responsivity of a calibrated photodiode.

PMID- 12211545
TI  - Polarization Talbot self-imaging with computer-generated, space-variant
      subwavelength dielectric gratings.
AB  - Self-imaging of a periodic space-variant polarized field is demonstrated. The
      field is created by use of space-variant subwavelength dielectric gratings. Our
      observations include self-imaging of the fields at the Talbot planes as well as
      the translation of incident polarization variation into intensity modulation at
      certain planes. We demonstrate the formation of a one-dimensional nondiffracting
      beam with uniform intensity and a nontrivial polarization structure.

PMID- 12211546
TI  - Volume grating couplers: polarization and loss effects.
AB  - We analyze the polarization-dependent performance and the loss performance of
      volume grating couplers using a leaky-mode approach in conjunction with rigorous
      coupled-wave analysis for two configurations: the volume grating in the cover
      layer and the volume grating in the waveguide. The angular dependence of TE and
      TM polarization coupling efficiency is studied, and designs for polarization
      dependent and polarization-independent couplers are presented for both
      configurations. Polarization-dependent couplers are obtained with an outcoupling
      angle close to normal. Polarization-independent couplers are obtained with
      outcoupling angles away from normal, 46.7 deg in the case of a volume grating in
      the cover layer and 54.4 deg in the case of a volume grating in the waveguide.
      The effect of loss on coupler performance is also analyzed. It is found that, for
      cases of practical importance, the effect of lossy coupler materials is small.
      The estimated loss for a commercially available material is 5 dB/cm. For TE
      polarized light and the volume grating in the waveguide, a loss of this magnitude
      reduces the coupling efficiency by less than 3%, whereas in the case of the
      volume grating in the cover layer, it reduces the coupling efficiency by less
      than 0.3%.

PMID- 12211547
TI  - Fresnel diffraction effects in the frontlight for a liquid-crystal display.
AB  - In a new type of illumination system for reflective liquid-crystal displays, the
      frontlight, unwanted shadows appear in certain viewing directions. It will be
      shown that for an accurate description of these shadows the geometrical optics
      approach is not satisfactory and that Fresnel diffraction has to be taken into
      account. A model for the diffraction effects was developed, and the predicted
      results correspond well to the measurements. In addition, some remarkable effects
      were explained from the theory of Fresnel zones.

PMID- 12211548
TI  - From the reflected spectrum to the properties of a fiber Bragg grating: a genetic
      algorithm approach with application to distributed strain sensing.
AB  - We describe a genetic algorithm approach to solve an inverse problem in optics,
      which determines the characteristics of a fiber Bragg grating from its reflected
      spectrum. The validity of the proposed method is demonstrated by use of a Bragg
      sensor for the measurement of nonlinear strain acting on a uniaxial aluminum test
      specimen.

PMID- 12211549
TI  - Multiple fiber Bragg grating sensor system using code-division multiple access.
AB  - We propose and demonstrate experimentally a multiple fiber Bragg grating sensor
      system that uses a LED as a light source and adapts the code-division multiple
      access method to separate individual sensor signals. We measured static and
      dynamic strains and cross-talk levels among sensor signals. With our proposed
      scheme, a low-cost sensor system can be designed with a fast response speed.
      Cross-talk levels between sensor signals are found to be below the -30-dB level.

PMID- 12211550
TI  - Design and plasma deposition of dispersion-corrected multiband rugate filters.
AB  - Inverse Fourier transform method has been commonly used for designing complex
      inhomogeneous optical coatings. Since it assumes dispersion-free optical
      constants, introducing real optical materials induces shifts in the position of
      reflectance bands in multiband inhomogeneous minus (rugate) filters. We propose a
      simple method for considering optical dispersion in the synthesis of multiband
      rugate filter designs. Model filters designed with this method were fabricated on
      glass and polycarbonate substrates by plasma-enhanced chemical vapor deposition
      of silicon oxynitrides and SiO2/TiO2 mixtures with precisely controlled
      composition gradients.

PMID- 12211551
TI  - Estimation of longitudinal resolution in optical coherence imaging.
AB  - The spectral shape of a source is of prime importance in optical coherence
      imaging because it determines several aspects of image quality, especially
      longitudinal resolution. Wide spectral bandwidth, which provides short coherence
      length, is sought to obtain high-resolution imaging. To estimate longitudinal
      resolution, the spectral shape of a source is usually assumed to be Gaussian,
      although the spectra of real sources are typically non-Gaussian. We discuss the
      limit of this assumption regarding the estimation of longitudinal resolution. To
      this end, we also investigate how coherence length is related to longitudinal
      resolution through the evaluation of different definitions of the coherence
      length. To demonstrate our purpose, the coherence length for several theoretical
      and real spectral shapes of sources having the same spectral bandwidth and
      central wavelength is computed. The reliability of coherence length computations
      toward the estimation of longitudinal resolution is discussed.

PMID- 12211552
TI  - Phase-shifting apodizers for increasing focal depth.
AB  - We propose the use of a phase-shifting apodizers to increase focal depth, and we
      study the axial and radial behavior of this kind of apodizer under the condition
      that the axial intensity distribution is optimized for high focal depth.

PMID- 12211553
TI  - Three-dimensional optical high-resolution profiler with a large observation
      field: foot arch behavior under low static charge studies.
AB  - Our aim is to describe a method for detecting small deformations from a three
      dimensional (3D) shape of large lateral dimensions. For this purpose the
      measurement method is based on the simultaneous utilization of several 3D optical
      systems and the phase-shifting technique. In this way, the following problems
      appear: optical distortion due to the large field observed, nonlinear phase-to
      height conversion, conversion of image coordinates into object coordinates for
      each 3D optical system, and coordinate unification of all optical systems. The
      resolution is 50 microm with a field of view of 320 mm x 150 mm. We used this
      system to study the 3D human foot arch deformation under low loads in vivo. First
      results indicate the hysteresis behavior of the human foot under a low load (50
      to 450 N).

PMID- 12211554
TI  - High-accuracy measurements of the refractive index and its temperature
      coefficient of calcium fluoride in a wide wavelength range from 138 to 2326 nm.
AB  - The refractive indices of synthetic calcium fluoride for 69 wavelengths from 138
      nm in the deep ultraviolet to 2326 nm in the near infrared were measured by the
      minimum-deviation method in a nitrogen environment. We made these measurements at
      20 degrees and 25 degrees C, respectively, to determine the thermal coefficients
      of the refractive index over this wide-wavelength region. These refractive
      indices were fitted to a four-term Sellmeier dispersion formula. The temperature
      coefficients of the refractive index were fitted to a Hoffman-type dispersion
      formula. The standard deviation of the residual between the observed values and
      the calculated values was 0.6 x 10(-6) for the refractive index and was 0.13 x
      10(-6)/degrees C for the temperature coefficient of the refractive index.

PMID- 12211555
TI  - Optical assessment of head-mounted displays in visual space.
AB  - The optics of head-mounted displays (HMDs) is designed from the pupil of the eye
      to the miniature display, and the optics is thus commonly solely assessed in the
      plane of the miniature display. Such assessment does not provide information that
      usefully interfaces with task-based performance metrics. We present a
      comprehensive framework for the assessment of the optics of HMDs in visual space,
      which applies to nonrotationally symmetric systems as well. Four key measures of
      visual performance are presented, and macro files were implemented to validate
      the framework. We illustrate the methods using an Erfle eyepiece.

PMID- 12211556
TI  - Colorimetry-based retardation measurement method with white-light interference.
AB  - A colorimetry-based retardation measurement (CBRM) method is presented. The
      specimen, between crossed polarizers, is illuminated with a white-light source.
      The retardation that is due to the birefringence of the specimen produces a white
      light interference color. The x, y chromaticity coordinates of the color produced
      are measured with a spectrophotometer. The resulting x, y values are compared
      with a retardation x, y database that we obtained by measuring the retardation
      with an accurate Senarmont compensator and the x, y chromaticity values along the
      length of a 0-4-order quartz wedge. The technique was validated by the
      measurement of a variety of retardation plates. The retardation accuracy (mean
      error) of the CBRM method is shown to be 3.6 nm. The resolution is +/-0.2 nm, and
      the measurement range is 5-2150 nm. The method substitutes for a polariscope and
      eliminates errors associated with quarter-wave plates. The CBRM method does not
      utilize any moving parts and thus is fast and can be automated.

PMID- 12211557
TI  - Prototype results of a phase-shifting interferometer capable of measuring the
      complex index and profile of a test surface.
AB  - Results are presented from a prototype phase-shifting interferometer capable of
      measuring both the real and the imaginary part of the complex index of refraction
      and the surface profile of a test surface. The three parameters of interest are
      extracted from the measured data by maximum-likelihood estimation theory. The
      performance of the system is quantitatively assessed with Cramer-Rao lower
      bounds. The results are shown to be strongly dependent on the quantization of the
      interferograms from the 8-bit CCD camera, the incident electric field amplitude,
      and the relative amplitude and phase difference of each polarized component
      through each arm of the interferometer.

PMID- 12211558
TI  - One-beam interferometer by beam folding.
AB  - A novel one-beam interferometer based on beam folding is described. The device
      resembles a Mach-Zehnder interferometer in which the two arms are located
      together in one collimated beam. Different halves of the same beam interfere with
      the help of a mirror--with its reflecting surface along the axis of the optical
      system--placed near the focal plane of the imaging lens. Phase-delay control is
      achieved by application of an electrical potential to a Pockels cell, which
      permits the use of techniques of phase-stepping interferometry.

PMID- 12211559
TI  - Interferometric measurement of the refractive-index distribution in plastic
      lenses by use of computed tomography.
AB  - A nondestructive measurement method that makes possible the measurement of a
      three-dimensional refractive-index distribution of any shape plastic lens is
      presented. In this method, a Mach-Zehnder interferometer and shearing
      interferometer are combined into a single optical system and are used
      selectively. Interference fringes of a test object that is immersed in matching
      liquid are detected at various rotation angles. And transmitted wave fronts are
      calculated with these interference fringes. Finally, the refractive-index
      distribution is obtained by computed tomography analysis. In addition, accurate
      control of the matching liquid temperature makes it possible to measure the
      absolute refractive index of the test object. This system has good performance
      with a measurement accuracy of 10(-4) or better peak to valley.

PMID- 12211560
TI  - Real-time color holographic interferometry.
AB  - A new optical technique based on real-time color holographic interferometry has
      been developed for analyzing unsteady aerodynamic wakes in fluid mechanics or for
      measuring displacements and deformations in solid mechanics. The technique's
      feasibility is demonstrated here. It uses three coherent wavelengths produced
      simultaneously by a cw laser (mixed argon and krypton). Holograms are recorded on
      single-layer panchromatic silver halide (Slavich PFG 03C) plates. Results show
      the optical setup can be adjusted to obtain a uniform background color. The
      interference fringe pattern visualized is large and colored and exhibits a single
      central white fringe, which makes the zero order of the interferogram easy to
      identify. An application in a subsonic wind tunnel is presented, in which the
      unsteady wake past a cylinder is recorded at high rate.

PMID- 12211561
TI  - Designing an optical disk lens without analytical definition of aspheric
      surfaces.
AB  - We have developed a new method to design aspheric lenses. The conventional
      technique is usually based on analytic definition of optical surfaces; in the new
      method discretely defined aspheres are used, and the final design is attained
      point by point with an iterative algorithm. Simulation results are compared with
      results obtained with conventional optical design software to prove that this new
      method is more effective and reliable for designing aspheric lenses, especially
      when the aspheric order is high.

PMID- 12211562
TI  - Photoelastic and acousto-optical properties of Cs2HgCl4 crystals.
AB  - We use a Mach-Zehdner interferometric technique to study the piezo-optical
      properties of Cs2HgCl4 crystals at room temperature. All piezo-optical (pi(mn))
      and photoelastic (p(in)) tensor constants are obtained. A substantial
      photoelastic effect and low ultrasonic velocities in these crystals determine a
      relatively high figure of merit M2 for isotropic diffraction (for a certain
      geometry of acousto-optical interactions, M2 approximately 110 x 10(-15) s3/kg).
      The new material may be considered, therefore, a candidate for applications in
      acousto-optical devices. The dependence of the acoustic walk-off angle on the
      direction of sound propagation is calculated for the principal crystallographic
      planes.

PMID- 12211563
TI  - Three-dimensional simulations of light propagation in periodic liquid-crystal
      microstructures.
AB  - A composite scheme based on the finite-difference time-domain method and a plane
      wave expansion method is developed and applied to the optics of periodic liquid
      crystal microstructures. This is used to investigate three-dimensional light-wave
      propagation in grating-induced bistable nematic devices with double periodicity.
      Detailed models of realistic devices are analyzed with emphasis on two different
      underlying surface-relief grating structures: a smooth bisinusoidal grating and a
      square-post array. The influence of the grating feature size is quantified.
      Device performance is examined in conjunction with an appropriate compensation
      layer, and the optimum layer thickness is determined for the different grating
      geometries.

PMID- 12211564
TI  - Modulation of retroreflection by controlled frustration of total internal
      reflection.
AB  - Retroreflective images are useful in outdoor application for which high
      legibility is required both during the day and in response to vehicular
      illumination. To date, all variable message retroreflective images have employed
      mechanical shutters as the switching mechanism. As an alternative, we propose a
      method for switching the total internal reflection effect used in retroreflectors
      by means of pneumatic actuation of surface treated polydimethylsiloxane gel. This
      approach is both effective and compatible with current large-scale manufacturing
      methods.

PMID- 12211565
TI  - Electric-field-induced motion of polymer cholesteric liquid-crystal flakes in a
      moderately conductive fluid.
AB  - Polymer cholesteric liquid-crystal flakes suspended in a fluid with nonnegligible
      conductivity can exhibit motion in the presence of an ac electric field. The
      plateletlike particles with a Grandjean texture initially lie parallel to the
      cell substrates and exhibit a strong selective reflection that is diminished or
      extinguished as the flakes move. Flake motion was seen within a specific
      frequency bandwidth in an electric field as low as 5 mV(rms)/microm. Flakes
      reoriented about their longest axis to align parallel to theapplied field, and a
      rise time of 560 ms was seen in a 40-mV(rms)/microm field at 100 Hz.

PMID- 12211566
TI  - Digital in-line holography of microspheres.
AB  - We have used digital in-line holography (DIH) with numerical reconstruction to
      image micrometer-sized latex spheres as well as ferrimagnetic beads suspended in
      gelatin. We have examined in detail theoretically and experimentally the
      conditions necessary to achieve submicrometer resolution of holographic
      reconstructions. We found that both transparent and opaque particles could be
      imaged with a resolution that was limited only by the wavelength of the light
      used. Simple inspection of intensity profiles through a particle allowed an
      estimate to be made of the particle's three position coordinates within an
      accuracy of a few hundred nanometers. When the derivative of a second-order
      polynomial fitted to the intensity profiles was taken, the X, Y, Z position
      coordinates of particles could be determined within +/-50 nm. More-accurate
      positional resolution should be possible with the help of more-advanced computer
      averaging techniques. Because a single hologram can give information about a
      large collection of distributed particles, DIH offers the prospect of a powerful
      new tool for three-dimensional tracking of particles.

PMID- 12211567
TI  - Epifluorescence collection in two-photon microscopy.
AB  - We present a simple model to describe epifluorescence collection in two-photon
      microscopy when one images in a turbid slab with an objective. Bulk and surface
      scattering determine the spatial and angular distributions of the outgoing
      fluorescence photons at the slab surface, and geometrical optics determines how
      efficiently the photons are collected. The collection optics are parameterized by
      the objective's numerical aperture and working distance and by an effective
      collection field of view. We identify the roles of each of these parameters and
      provide simple rules of thumb for the optimization of the epifluorescence
      collection efficiency. Analytical results are corroborated by Monte Carlo
      simulation.

PMID- 12211568
TI  - Evaluation of a variable-addressability monocular.
AB  - A variable-addressability monocular that provides a variation in resolution
      across the field of view is presented. The variation in resolution is based on
      the eye's visual-acuity curve. A prototype has been built that does a nonlinear
      mapping of the pixels, designed to work most efficiently with the human visual
      system. In addition a conventional, uniform-addressability prototype has been
      built. A human-factors experiment is presented that directly compares the
      variable-addressability prototype with the conventional system. The human-factors
      results show that the variable-addressability prototype provides better
      resolution 13% of the time but is 15% slower in use than the uniform
      addressability prototype.

PMID- 12211569
TI  - Simultaneous measurement of current and voltage by use of one bismuth germanate
      crystal.
AB  - An optical fiber sensor is presented that allows current and voltage to be
      measured simultaneously by use of only one block of bismuth germanate crystal.
      The polarized light from the sensing crystal is split into two light beams: One
      beam is utilized for current measurement based on the Faraday effect, and the
      other one is utilized for voltage measurement based on the Pockels effect.
      Compared with the existing optical sensors that can measure current and voltage
      simultaneously, this sensor is simple and inexpensive and allows measurement of
      electric power. The simultaneous measurements of ac electric current from 0.05 to
      10 A, voltage from 1 to 235 V, and power from 2 to 1000 W have been achieved with
      good linear-response characteristics. The input characteristics and measurement
      uncertainties that are due to the nonlinear error of the sensing system are also
      discussed.

PMID- 12211570
TI  - Sub-quarter-wave multilayer coatings with high reflectance in the extreme
      ultraviolet.
AB  - Multilayer coatings with a small number of layers were designed and prepared to
      provide an increase in normal-incidence reflectance in the extreme ultraviolet
      compared with the reflectance of available single-layer coatings, namely, SiC,
      B4C, and Ir. Multilayers were designed to produce coatings with the highest
      possible reflectance at 91.2 and at 58.4 nm. At these wavelengths all the
      materials absorb radiation strongly, but still a reflectance enhancement can be
      obtained by means of sub-quarter-wave multilayer coatings with two or more
      different materials. Sub-quarter-wave multilayer coatings based on Al, MgF2,
      diamondlike carbon, B4C, SiC, and Ir showed higher reflectance than single-layer
      coatings of SiC and B4C not only at the target wavelength but in a wide band
      ranging from 50 nm to the 121.6-nm H Lyman-alpha line. Multilayer coatings
      suffered some reflectance degradation over time. However, after approximately 80
      100 days of aging in a desiccator, the reflectance for the multilayer coatings
      was greater than for the single-layer coatings.

PMID- 12211571
TI  - Polarized light scattering by dielectric and metallic spheres on silicon wafers.
AB  - The polarization and intensity of light scattered by monodisperse polystyrene
      latex and copper spheres, with diameters ranging from 92 to 218 nm, deposited on
      silicon substrates were measured with 442-, 532-, and 633-nm light. The results
      are compared with a theory for scattering by a sphere on a surface, originally
      developed by others [PhysicaA 137,209 (1986)], and extended to include coatings
      on the sphere and the substrate. The results show that accurate calculation of
      the scattering of light by a metal sphere requires that the near-field
      interaction between the sphere and its image be included in acomplete manner. The
      normal-incidence approximation does not suffice for this interaction, and the
      existence of any thin oxide layer on the substrate must be included in the
      calculation.

PMID- 12211572
TI  - Fabrication and optical properties of metastable Cu-Ag alloys.
AB  - A series of single-phase metastable Cu-Ag solid solutions was deposited by
      magnetron sputtering at liquid-nitrogen temperature. The lattice constant
      increases with increasing Ag content. The spectroscopic ellipsometer measurements
      clearly show that with increasing Ag content, the Cu-like and Ag-like absorption
      edges in the visible wavelength range shift continuously toward the high-energy
      and the low-energy sides, respectively.

PMID- 12211573
TI  - Characterization of the supermirror hard-x-ray telescope for the InFOCmuS balloon
      experiment.
AB  - A hard-x-ray telescope is successfully produced for balloon observations by
      making use of depth-graded multilayers, or so-called supermirrors, with platinum
      carbon (Pt/C) layer pairs. It consists of four quadrant units assembled in an
      optical configuration with a diameter of 40 cm and a focal length of 8 m. Each
      quadrant is made of 510 pieces of coaxially and confocally aligned supermirrors
      that significantly enhance the sensitivity in an energy range of 20-40 keV. The
      configuration of the telescope is similar to the x-ray telescope onboard Astro-E,
      but with a longer focal length. The reflectivity of supermirrors is of the order
      of 40% in the energy range concerned at a grazing angle of 0.2 deg. The effective
      area of a fully assembled telescope is 50 cm2 at 30 keV. The angular resolution
      is 2.37 arc min at half-power diameter 8.0 keV. The field of view is 12.6 arc min
      in the hard-x-ray region, depending somewhat on x-ray energies. We discuss these
      characteristics, taking into account the figure errors of reflectors and their
      optical alignment in the telescope assembly. This hard-x-ray telescope is
      unanimously afforded in the International Focusing Optics Collaboration for
      muCrab Sensitivity balloon experiment.

PMID- 12211574
TI  - Absorption and scattering images of heterogeneous scattering media can be
      simultaneously reconstructed by use of dc data.
AB  - We present a carefully designed phantom experimental study aimed to provide solid
      evidence that both absorption and scattering images of heterogeneous scattering
      media can be reconstructed independently from dc data. We also study the
      important absorption-scattering cross-talk issue. In this regard, we develop a
      simple normalizing scheme that is incorporated into our nonlinear finite-element
      based reconstruction algorithm. Our results from the controlled phantom
      experiments show that the cross talk of an absorption object appearing in
      scattering images can be eliminated and that the cross talk of a scattering
      object appearing in absorption images can be reduced considerably. In addition,
      these carefully designed phantom experiments clearly suggest that both absorption
      and scattering images can be simultaneously recovered and quantitatively
      separated in highly scattering media by use of dc measurements. Finally, we
      discuss our results in light of recent theoretical findings on nonuniqueness for
      dc image reconstruction.

PMID- 12211575
TI  - Salmonella surveillance: a global survey of public health serotyping.
AB  - To better understand the global epidemiology of salmonellosis and the national
      surveillance programmes used for salmonella infections in humans, we conducted a
      global survey of the 191 WHO Member States. We gathered information on the total
      number of salmonella isolates serotyped, and the 15 most commonly isolated
      serotypes from humans in 1990 and 1995. Of the 104 countries that responded, 76
      (73.1%) conducted public health surveillance for salmonella and 69 of these
      (90.8%) conducted serotyping as part of the surveillance. Fifty-nine countries
      (56.7% of those responding) provided information about the most commonly isolated
      serotypes in 1995. Three serotypes, Enteritidis, Typhimurium and Typhi accounted
      for 76.1% of all isolates reported in 1995. One of these three was the most
      common serotype identified in 93.2% of countries reporting data for that year. In
      1995, Enteritidis was the most frequently isolated serotype in 35 countries,
      followed by Typhi (12 countries) and Typhimurium (8 countries). The global
      pandemic of Salmonella Enteritidis continued to expand. The mean national
      proportion of all salmonella isolates that were Enteritidis increased globally
      from 25.6% in 1990 to 36.3% in 1995. Serotyping is a frequently used component of
      a public health response to the global challenge of salmonellosis. Support for
      serotyping as part of national salmonella surveillance, and for rapid
      international communication of the results via a new WHO electronic website will
      help target future prevention strategies.

PMID- 12211576
TI  - Partial VP1/2A gene sequence based molecular epidemiology of wild type 1
      poliovirus isolates from some parts of India.
AB  - Genomic variability within the sequences of VP1/2A junction among polioviruses
      from across the globe has revealed the existence of several endemic genotypes and
      their epidemiological inter-relationships; but such data on Indian isolates are
      scanty. The present work was intended to ascertain the persistence and
      transmission pattern of different genotypes of wild type 1 polioviruses
      circulating in India. Forty-eight wild type 1 poliovirus isolates obtained from
      different parts of India during 1996-8 were subjected to RT-PCR and nucleotide
      sequencing using M13 tailed primers. A 293 base pair region was amplified and
      sequenced for genetic variation study. Considering the 15% divergence of the
      sequences from Sabin 1, the isolates from six different states of India confirmed
      a single dominant genotype 4. Phylogenetic analysis revealed the circulation and
      active inter-state transmission of many genetically distinct strains of wild
      poliovirus type 1 belonging to genotype 4. This warrants the need for insisting
      on more efficient surveillance mechanisms so as to assess the impact of an
      extensive pulse polio immunization programme in India.

PMID- 12211577
TI  - An outbreak of hepatitis A among homosexuals linked to a family outbreak.
AB  - Several outbreaks of hepatitis A occurred in Norway in 1995-8. Molecular
      epidemiology was used to follow the spread of hepatitis A virus in the
      population. Distinct strains of hepatitis A virus (HAV) were detected by reverse
      transcriptase-polymerase chain reaction (RT-PCR) and subsequent sequencing in
      serum from patients in different communities at risk of infection. Two HAV
      strains were detected in an outbreak among 26 men having sexual contact with
      other men. One of these strains was also detected in a geographically limited
      family outbreak. The family outbreak was first believed to be acquired abroad.
      The sequence information linked the two outbreaks, and epidemiological and
      serological analyses revealed the transmission route. This study demonstrates the
      importance of molecular epidemiology in outbreak investigation, surveillance and
      monitoring of hepatitis A in the population.

PMID- 12211578
TI  - Evaluation of hepatitis C surveillance in Poland in 1998.
AB  - The aim was to evaluate hepatitis C surveillance in Poland during 1998. Hepatitis
      C reports were obtained from epidemiology offices. Public health staff were
      interviewed to collect information on surveillance operations. To estimate the
      proportion of acute cases among the total reported, a study was conducted in the
      Warsaw district to validate case reports. A total of 1661 (97.2%) hepatitis C
      cases were studied. Hepatitis C surveillance was timely and acceptable to the
      user, but did not provide a number of information elements required to
      differentiate acute from chronic cases of infection. Of the 268 case reports
      available in the Warsaw district, only 15 (5.6%) met the acute hepatitis C case
      definition. It is concluded that hepatitis C surveillance in Poland cannot
      provide useful incidence estimates and information regarding risk factors for
      acute infection. A strict case definition and a modified case form with specific
      questions for HCV transmission routes should be applied.

PMID- 12211579
TI  - A large hotel outbreak of Norwalk-like virus gastroenteritis among three groups
      of guests and hotel employees in Virginia.
AB  - A large outbreak of acute gastroenteritis occurred among three different groups
      of guests and the employees of a Virginia hotel within a 2-week period in
      November 2000. At least 76 of the hotel's guests and 40 hotel employees had acute
      gastroenteritis during this period. All tested ill persons were infected with the
      same strain of Norwalk-like virus, as shown by cloning and sequencing of virus
      detected in stool specimens from the three guest groups and the employees.
      Epidemiologic investigation suggested food as the probable source for the guests.
      Most of the employees, including those sick, did not eat in the hotel, suggesting
      that environmental contamination and person-to-person transmission could have
      contributed to the outbreak. The disease continued to spread in the hotel,
      passing from one guest group to another, by food, environmental contamination,
      and/or by person-to-person transmission through infected employees and guests.
      The study describes procedures implemented to control the outbreak and makes
      recommendations for future outbreak control.

PMID- 12211580
TI  - A prolonged outbreak of Norwalk-like calicivirus (NLV) gastroenteritis in a
      rehabilitation centre due to environmental contamination.
AB  - An outbreak of Norwalk-like calicivirus (NLV) gastroenteritis occurred in a
      rehabilitation centre in southern Finland between December 1999 and February
      2000. An epidemiological investigation was conducted to determine the source and
      extent of the outbreak. More than 300 guests and staff members became ill during
      the outbreak. No food or activity in the centre could be linked epidemiologically
      to illness. NLV genogroup II was detected by RT-PCR in stool samples of
      symptomatic guests and employees. All strains reacted similarly with the
      microplate hybridization probe panel and showed the same nucleotide sequence,
      indicating that they represented the same NLV strain. Food and water samples were
      negative for NLV, whereas NLV was detected in three environmental specimens. The
      strains from patients and environment were identical based on microplate
      hybridization probes, suggesting that environmental contamination may have been
      important for the spread of calicivirus and the protracted course of the
      outbreak.

PMID- 12211581
TI  - Inter-test reliability of the anti-RESA indices based on ELISA tests using
      eluates from whole blood spots dried on filter paper.
AB  - The ring-infected erythrocyte surface antigen (RESA), is one of the falciparum
      malaria vaccine candidates rarely studied in Brazil. Fieldwork logistics to
      conduct serology studies is simplified when eluates from whole blood dried on
      filter paper can be used. Therefore, this study aimed to assess the inter-test
      reliability for the anti-RESA ELISA-based indices using eluates from filter paper
      and from serum samples. The study population consisted of 210 individuals
      (Brazil) from whom matched samples were collected. Anti-RESA ELISA-based index
      means (+/- S.D.) were 15.29% (+/-28.13%) for filter paper and 11.79% (+/-23.67%)
      for serum samples. The intra-class correlation coefficient was estimated to be
      82.38%, indicating high test reliability. However, there was a significant
      tendency for filter paper test results to have higher values than serum sample
      test results (P < 0.001). Explanations for this finding may be the presence of
      haemoglobin in the eluates from filter paper, which may interfere with ELISA
      testing.

PMID- 12211582
TI  - A clarification of transmission terms in host-microparasite models: numbers,
      densities and areas.
AB  - Transmission is the driving force in the dynamics of any infectious disease. A
      crucial element in understanding disease dynamics, therefore, is the
      'transmission term' describing the rate at which susceptible hosts are
      'converted' into infected hosts by their contact with infectious material.
      Recently, the conventional form of this term has been increasingly questioned,
      and new terminologies and conventions have been proposed. Here, therefore, we
      review the derivation of transmission terms, explain the basis of confusion, and
      provide clarification. The root of the problem has been a failure to include
      explicit consideration of the area occupied by a host population, alongside both
      the number of infectious hosts and their density within the population. We argue
      that the terms 'density-dependent transmission' and 'frequency-dependent
      transmission' remain valid and useful (though a 'fuller' transmission term for
      the former is identified), but that the terms 'mass action', 'true mass action'
      and 'pseudo mass action' are all unhelpful and should be dropped. Also, contrary
      to what has often been assumed, the distinction between homogeneous and
      heterogeneous mixing in a host population is orthogonal to the distinction
      between density- and frequency-dependent transmission modes.

PMID- 12211583
TI  - Drug resistances in salmonella isolates from animal foods, italy 1998-2000.
AB  - We investigated the distribution of serotypes and patterns of drug resistance of
      206 strains of salmonella isolated in southern Italy in the years 1998-2000 from
      raw food of animal origin, faeces of food animals and animal feed. To improve
      knowledge of mobile genetic elements carrying the resistance genes, some
      molecular features were also investigated within isolates resistant to three or
      more antibiotics. A high proportion of isolates, 52.2% and 37.7%, respectively,
      belonging to both Typhimurium and other serotypes of animal origin, proved to be
      multidrug resistant. The DT104 complex specific multidrug pattern of resistance
      was quite infrequent among isolates other than Typhimurium, but resistances to
      nalidixic acid and kanamycin were more frequent within these last ones (36.9% vs.
      11.4% and 56.5% vs. 2.2%, respectively). Class I integrons were detected in
      isolates of Typhimurium and seven different serotypes. The relevance of food
      animal environment as a drug resistance reservoir and animal food as a potential
      resistance gene vehicle between the farm and human ecological niches is confirmed
      by our findings.

PMID- 12211584
TI  - Escherichia coli O157:H7 infection in cows and calves in a beef cattle herd in
      Alberta, Canada.
AB  - Escherichia coli O157:H7 infection of cows and calves in a naturally-infected
      beef cattle herd in Alberta, Canada, was investigated over 2 years, encompassing
      two calf production cycles. In both years of the study, E. coli O157:H7 was
      isolated from the faeces of cows shortly after but not before parturition in late
      winter: 6/38 (16%) in 1996 and 13/50 (26%) in 1997. At < 1 week post-partum,
      13/52 (25%) calves born in 1997 were shedding the organism. Faecal shedding of E.
      coli O157:H7 by cows and calves continued over the 7 weeks that they were in the
      calving pens, with the organism being isolated from the faeces of 2-18% of cows
      and 23-26% of calves during this period. Five weeks after they were moved onto a
      native grass pasture, all the calves and all but one cow in 1997 had ceased
      shedding the organism. When the calves were weaned in the fall, E. coli O157:H7
      was isolated from the faeces of 0-1.5% of the calves 1 week prior to weaning and
      from 6-14% of the calves within 2 weeks after weaning. Parturition, calving pens
      and weaning appear to be important factors in maintaining E. coli O157:H7
      infections in this beef cattle herd. Isolates from cows and calves during the
      immediate post-partum period were mostly of the same pulsed-field gel
      electrophoresis (PFGE) type of E. coli O157:H7. Similarly, at weaning a common
      PFGE type of E. coli O157:H7, which differed slightly from the post-partum PFGE
      type, was isolated from the calves. These typing data suggest a common source of
      infection for the animals as well as demonstrate clonal turnover of resident
      populations of this pathogen.

PMID- 12211585
TI  - A long-term study on the prevalence of shiga toxin-producing Escherichia coli
      (STEC) on four German cattle farms.
AB  - The occurrence of Shiga toxin-producing Escherichia coli (STEC) was studied on
      four cattle farms. STEC were detected in 29-82% of the cattle. STEC with
      additional EHEC markers were detected on all farms. The occurrence of the
      complete virulence marker pattern (stx1 and/or stx2, eae, EHEC(hlyA), katP, espP)
      was correlated with the presence of known STEC serotypes. STEC O26:H11 and
      O165:H25 with the complete pattern of virulence markers were the most prevalent.
      STEC O157 (H7/H-) STEC O103:H2 and STEC O145:H- were found sporadically. Five
      clonal subgroups of the STEC O26:H11 isolates were identified by pulsed-field gel
      electrophoresis. STEC O26:H11 were present in three groups of cattle. This
      serotype was detected in a single group over the entire fattening period. Most
      STEC O26:H11 with the complete pattern of potential virulence markers were found
      in clinically healthy cattle. These animals may represent a risk factor for
      farmers and consumers.

PMID- 12211586
TI  - Prevalence of campylobacters in chicken flocks during the summer of 1999 in
      Finland.
AB  - In order to determine the prevalence of campylobacter positive broiler flocks in
      Finland, every flock from all three major slaughterhouses was studied during the
      period from 1 May to 30 September 1999. Caecal samples were taken in the
      slaughterhouses from five birds per flock. A total of 1132 broiler flocks were
      tested and 33 (2.9%) of those were campylobacter positive. Thirty-one isolates
      were C. jejuni and two isolates were C. coli. Isolates were serotyped for heat
      stable antigens (Penner) and genotyped with pulsed-field gel electrophoresis
      (PFGE). The most common serotypes were serotypes 6, 7, 12 and 4-complex. Together
      with SmaI and KpnI patterns there were 18 different PFGE genotypes. Simultaneous
      monitoring of chicken flocks and typing of the isolates produced data which can
      be used to study the epidemiology of campylobacters in chicken as well as their
      role in human infections.

PMID- 12211587
TI  - Human salmonellosis associated with young poultry from a contaminated hatchery in
      Michigan and the resulting public health interventions, 1999 and 2000.
AB  - Although approximately 95% of disease caused by nontyphoidal salmonella is
      transmitted by foodborne vehicles, four documented salmonella outbreaks in the
      1990s have been traced to contact with young poultry. No environmental studies of
      source hatcheries were completed. This case-control study was performed by
      comparing culture-confirmed Salmonella Infantis in Michigan residents, identified
      between May and July 1999, with two age- and neighbourhood-matched controls.
      Eighty environmental and bird tissue samples were collected from an implicated
      hatchery; all salmonella isolates underwent pulsed-field gel electrophoresis
      (PFGE) analysis. The study included 19 case-patients sharing the same PFGE
      subtype and 37 matched controls. Within 5 days before illness onset, 74% of case
      patients resided in households raising young poultry compared with 16% of
      controls (matched OR 19.5; 95% CI 2.9, 378.1). Eight hatchery samples yielded
      Salmonella Infantis with PFGE subtypes matching the patients' isolates. This
      investigation identified birds from a single hatchery as the source of human
      illness and confirmed the link by matching PFGE patterns from humans, birds and
      the hatchery environment. Subsequent public health interventions reduced, but did
      not eliminate, transmission of poultry-associated salmonellosis. Five additional
      PFGE-linked cases were identified in Spring 2000, necessitating quarantine of the
      hatchery for depopulation, cleaning and disinfection.

PMID- 12211588
TI  - Spread of Staphylococcus aureus resistant to penicillin and tetracycline within
      and between dairy herds.
AB  - One hundred and seven bovine isolates of penicillin and tetracycline resistant
      Staphylococcus aureus, recovered from 25 different dairy herds in various parts
      of Norway, were characterized using antimicrobial susceptibility testing,
      multilocus enzyme electrophoresis, ribotyping, plasmid analysis and serotyping of
      capsular polysaccharide. Forty-one isolates from one particular herd, 37 isolates
      from 5 herds that used a common pasture and milking parlour in summer and 21
      isolates from 12 herds in 8 different counties belonged to the same strain. The
      remaining 8 isolates, which originated from herds in 5 different counties, were
      assigned to 6 different strains. Seven out of these 8 isolates had the same
      plasmid restriction profile. In conclusion, penicillin and tetracycline resistant
      S. aureus occurring in dairy herds in Norway mainly seems to represent one
      particular strain that has achieved widespread distribution or belong to one of
      several different strains carrying identical plasmids.

PMID- 12211589
TI  - Transmission of Actinobacillus pleuropneumoniae in pigs is characterized by
      variation in infectivity.
AB  - Ten transmission trials with Actinobacillus pleuropneumoniae were carried out.
      The observed transmission was highly variable, which was surprising since the
      design of the trials was very similar. We investigated whether the variable
      transmission could be explained by variation in infectivity of A.
      pleuropneumoniae infected pigs. We looked for measurable characteristics, which
      could be indicative for infectious pigs or for the level of infectivity. The
      characteristic that appeared to be most indicative for a pig being infectious was
      an A. pleuropneumoniae positive tonsil at necropsy. The characteristic that was
      correlated to the level of infectivity was the number of A. pleuropneumoniae
      colonies isolated from the nasal swab, i.e. the probability for an infectious pig
      to infect a susceptible pig was tenfold higher on days where at least ten
      colonies were isolated. In this study it is shown that it is possible to measure
      the bacterial transmission of A. pleuropneumoniae under controlled circumstances
      if variation in infectivity is taken into account.

PMID- 12211590
TI  - Comparison of vaccination strategies for the control of dog rabies in Machakos
      District, Kenya.
AB  - Demographic and epidemiological field data were used in a deterministic model to
      describe dog rabies transmission in Machakos District, Kenya and to predict the
      impact of potential vaccination strategies for its control. The basic
      reproduction number (R0) was estimated to be 2.44 (1.52-3.36, 95% confidence
      limits). There were three key model predictions. The first was that a threshold
      dog density (K(T)) of 4.5 dogs km(-2) (3.8-5.2 dogs km(-2), 95% confidence
      limits) was required to maintain transmission. The second was that the estimated
      annual vaccination rate of 24% failed to decrease incidence and actually
      increased the stability of transmission and may be counter-productive. Thirdly,
      to control rabies, it was predicted that 59% (34%-70%, 95% confidence limits) of
      dogs should be vaccinated at any one time. This requires approximately 70%
      coverage for annual but only 60% coverage for semi-annual vaccination campaigns.
      Community-level vaccination trials are needed to test these predictions.

PMID- 12211591
TI  - Faecal contamination and enterotoxigenic Escherichia coli in street-vended chili
      sauces in Mexico and its public health relevance.
AB  - The street-vended food industry provides employment and cheap ready-to-eat meals
      to a large proportion of the population in developing countries like Mexico, yet
      little is known about its role in the transmission of food borne diseases (FBD).
      Because of its wide consumption, street-vended chili sauces in Mexico are
      potential vehicles of FBD. An observational study was performed in Mexico City
      collecting 43 street-vended chili sauces. These sauces were prepared under poor
      hygienic conditions of handling and selling. Consumers add 4-8 ml of chili sauce
      per taco, ingest 2-5 tacos per meal and on average, 50 consumers frequent a stall
      per day. Seventeen (40%) samples were faecally contaminated and 2(5%) sauces
      harboured sufficient enterotoxigenic Escherichia coli to cause disease.
      Weestimate that the consumption of only one of these chili sauces could result in
      ETEC disease inat least 21,000 consumers per year, making them important
      potential vehicles of FBD.

PMID- 12211592
TI  - Molecular epidemiology of nalidixic acid-resistant campylobacter isolates from
      humans and poultry by pulsed-field gel electrophoresis and flagellin gene
      analysis.
AB  - To investigate the potential of poultry products as the source of human
      infections associated with quinolone-resistant campylobacters, 140 human and 75
      poultry isolates of nalidixic acid-resistant campylobacters were collected
      between 1996 and 1998, and analysed by two molecular typing methods. By the
      analysis of restriction fragment length polymorphism of the flagellin gene, 33
      distinct patterns were obtained, with 18 of which shared by both human (89%) and
      poultry (93%) isolates. By the pulsed-field gel electrophoresis of SmaI
      restricted macrofragments, 105 different profiles were obtained, and 11 were
      found in both human (40%) and poultry (23%) isolates. When the two typing methods
      were combined, 112 unique genotypes were obtained, 11 of which were shared by
      both populations, including 53 (38%) human isolates and 14 (19%) poultry
      isolates. Although domestic poultry products are still important sources of the
      quinolone-resistant campylobacter infections in humans, there are other factors
      that might contribute to these increasing infections simultaneously. A more
      stringent policy in the use of antimicrobial agents in food animals can no longer
      be ignored.

PMID- 12211593
TI  - Decline in epidemic of multidrug resistant Salmonella typhi is not associated
      with increased incidence of antibiotic-susceptible strain in Bangladesh.
AB  - Since 1987, multidrug resistant (MDR) strains of Salmonella Typhi, resistant
      simultaneously to ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole,
      have caused epidemics of severe typhoid fever in Asia and Africa. A retrospective
      analysis of blood culture results (1989-96) in a Diarrhoea Treatment Centre in
      Dhaka, Bangladesh detected MDR strains in 0.3% (8 of 2793) of samples in 1990.
      The isolation rate peaked to 3.2% (240 of 7501) in 1994 (P < 0.01) and decreased
      to 1.8% (165 of 9348) in 1995 and further to 1.0% (82 of 8587) in 1996 (P < 0.01
      compared to 1994) indicating the emergence and decline of MDR typhoid epidemic.
      Ten of 15 MDR strains tested had a 176 kb conjugative R plasmid that mediates
      resistance to ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole to
      Escherichia coli K12. Unlike MDR strains, the isolation rate (approximately 3.3%)
      of susceptible S. Typhi remained remarkably unchanged during the study. The
      significant decrease in isolation of MDR strains suggests that cheaper and
      effective first-line antibiotics may re-emerge as drugs of choice for the
      treatment of typhoid fever in Bangladesh.

PMID- 12211594
TI  - An outbreak of Salmonella enteritidis phage type 34a infection in primary school
      children: the use of visual aids and food preferences to overcome recall bias in
      a case control study.
AB  - Outbreaks of infectious intestinal disease are common in schools. Case control
      studies are useful in the investigation of infectious disease outbreaks but the
      time interval between illness and investigation can lead to recall bias,
      particularly in young children. We describe an outbreak of Salmonella enteritidis
      phage type 34a infection involving 54 clinical cases in two adjacent schools, and
      a novel approach to overcome recall bias. The likely dates of infection were
      identified from the epidemic curve. We created a visual display of the menu from
      those days and asked 9 cases and 18 matched controls to identify their food
      preferences from this display. Preference for chocolate mouse was significantly
      associated with illness (P = 0.006). The results of the case control study agreed
      with the findings of the environmental investigation. We believe our approach
      could be used in other circumstances, where subjects are young children or recall
      bias is a concern.

PMID- 12211596
TI  - Combinations of putative virulence markers in typical and variant
      enteroaggregative Escherichia coli strains from children with and without
      diarrhoea.
AB  - Enteroaggregative Escherichia coli (EAEC) is defined by the ability to produce
      aggregative adherence (AA) to cultured cells. We analysed 128 EAEC strains,
      isolated from children with and without diarrhoea, regarding the presence of 11
      EAEC virulence genes. Seventy strains carried and 58 lacked the EAEC probe
      sequence; 17 probe positive and 31 probe negative strains showed variations in
      the AA pattern. All EAEC probe positive strains carried at least one EAEC marker;
      aspU (94.3%), irp2 (91.4%), and aggR (74.3%) were the most prevalent. Conversely,
      among the EAEC probe negative strains, 41.4% were devoid of any marker and astA
      predominated (44.8%). No significant statistical difference in the prevalence of
      any marker between cases and controls in both EAEC probe groups or AA variants
      was found. We suggest that the EAEC probe positive strains may have a higher
      pathogenic potential or alternatively, EAEC probe negative strains may harbour
      virulence factors as yet undescribed.

PMID- 12211595
TI  - Isolation and characterization of enterohaemorrhagic Escherichia coli O157:1H7
      from cattle in Belgium and Poland.
AB  - EHEC O157 were isolated from faeces of Belgian and Polish beef slaughter cattle.
      In Belgium, 1281 faecal samples were analysed by immunomagnetic separation [IMS]
      after enrichment in buffered peptone water from June 1998 till July 1999. Eighty
      one samples (6.3%) were positive for E. coli O157. Phage type 8 was most
      frequently found. Bulls between 1 and 2 years old, slaughtered in September and
      October were most frequently found positive. Atypical biochemical features were
      observed in some isolates: 22 (27%) isolates were urease positive and 1 (1.2%)
      isolate was unable to ferment lactose. In Poland, 551 faecal samples, taken from
      January 1999 till December 1999, were examined using exactly the same techniques.
      Four faecal samples (0.7%) were positive for O157 EHEC, yielding seven phage type
      8 isolates. All positive samples were from cattle younger than 2 years. Positive
      samples occurred in August, September and October.

PMID- 12211597
TI  - The epidemiology of glycopeptide-resistant enterococci on a haematology unit-
      analysis by pulsed-field gel electrophoresis.
AB  - As part of an interventional study to determine glycopeptide-resistant
      enterococci (GRE) acquisition on a three-ward haematology unit, rectal swabs were
      taken weekly from 293 patients recruited to the study between June 1995 and
      December 1996. The GRE isolates obtained from the first positive rectal swab from
      120 colonized patients, the isolates from 7 patients with clinical infection and
      43 isolates obtained from the ward environment were compared by pulsed-field gel
      electrophoresis (PFGE). Sixty-three of 120 patients were colonized by one of
      strains A-H, while 49 were colonized by unique strains. The first 18 weeks were
      associated with the highest prevalence of GRE by rectal swab, with a single
      strain A responsible for 52% of acquisitions on ward 2, 22% on ward 3 and 36% on
      ward 4. Other smaller ward associated clusters were evident. Environmental
      sampling of ward 2 during this time showed that all but 2 of 30 isolates were
      indistinguishable from strain A. As the GRE prevalence fell, rectal swab and
      environmental isolates became more heterogeneous, and strain A disappeared after
      week 55. GRE prevalence rose again in the final 15 weeks of the study, and a new
      predominant strain B emerged on ward 2 responsible for 50% of new acquisitions.
      In the seven patients with clinical infection with GRE, the clinical isolates
      were compared with the contemporaneous rectal swab isolate, and were found to be
      the same in only two cases. An analysis of five long-term carriers colonized for
      a median of 19 weeks (range 11-34) showed colonization with at least two and in
      one case six distinct strains, raising the question of how many strains may be
      colonizing a patient at any one time, and suggesting that multiple colonies
      should be analysed. These data suggest that cross-infection was an important
      factor in the spread of GRE when the colonization rate was high.

PMID- 12211598
TI  - Risk factors for pneumonia in infants and young children and the role of solid
      fuel for cooking: a case-control study.
AB  - We evaluated the risk factors for childhood pneumonia with particular reference
      to indoor air-pollution associated with solid fuel use for cooking (e.g. coal,
      wood, dung), using a case-control study in a children's hospital in Calcutta.
      Cases were 127 children aged 2-35 months of either sex admitted with pneumonia
      and controls were 135 children attending their immunization clinic. Solid fuel
      use (odds ratio = 3.97, CI = 2.00-7.88), history of asthma in the child (OR =
      5.49, CI = 2.37-12.74), poor economic status indicator (OR = 4.95, CI = 2.38 to
      10.28), keeping large animals (OR = 6.03, CI = 1.13-32.27) were associated with
      high risk of pneumonia after adjusting for confounding (logistic regression
      analysis). Nearly 80% of people in India use such smoke producing fuel and the
      population attributable risk would be very high. This finding has important
      health policy implications. Furthermore, history of asthma is a useful prognostic
      indicator for early action for prevention of severe pneumonia.

PMID- 12211599
TI  - Haemophilus influenzae type b and cross-reactive antigens in natural Hib
      infection dynamics; modelling in two populations.
AB  - Natural immunity to Haemophilus influenzae type b (Hib) invasive disease is based
      on antibodies arising in response to encounters with Hib or cross-reactive (CR)
      bacteria. The relative importance of Hib and CR contacts is unknown. We applied a
      statistical model to estimate the total rate of immunizing infections of Hib and
      CR prior to wide-scale vaccinations in Finland and the UK. The average rates of
      these contacts were 0.7 and 1.2 per year per child in Finland and the UK,
      respectively. Using a rough estimate of 0.1 Hib acquisitions per year per child
      in the UK based on carriage rates, the proportion of Hib among all immunizing
      contacts was in the order of 10%, suggesting that CR bacteria have a major role.
      In general, varying frequency of CR contacts may explain some differences in the
      pre-vaccination incidence and age-distribution of invasive disease in different
      countries.

PMID- 12211600
TI  - Prevalence of antibodies to Brucella spp. and risk factors related to high-risk
      occupational groups in Eritrea.
AB  - In a study of three high-risk occupational groups using Rose Bengal and
      complement fixation tests, the highest prevalence (7.1%) was found among dairy
      farm workers and owners in randomly selected dairy-cattle farms, followed by
      veterinary personnel (4.5%) and inhabitants in pastoralist areas (3.0%). There
      was no evidence for significant differences between the three populations. Among
      dairy farm workers, a higher risk was associated with the presence of sheep in
      the farm (OR = 13.2, CI = 2.2-76.7). In the pastoral area, a high risk was linked
      to having close contact with animals (OR = 6.32, CI = 0.88-infinity), while a
      reduced risk was seen for contact with cattle (OR = 0.18, CI = 0-1.30). Symptoms
      suggestive of brucellosis were more commonly observed among the dairy farm
      workers, mainly found in the highlands, than among the pastoralist area
      inhabitants, where malaria is prevalent. The study documents not only the
      presence of serological and clinical evidence of human brucellosis, but also risk
      factors related to it in Eritrea, for the first time.

PMID- 12211601
TI  - A population-based estimate of the burden of diarrhoeal illness in the United
      States: FoodNet, 1996-7.
AB  - This study was performed to better understand and more precisely quantify the
      amount and burden of illness caused by acute diarrhoea in the United States
      today. A telephone-based population survey was conducted between 1 July, 1996,
      and 31 June, 1997, in sites of the Foodborne Diseases Active Surveillance Network
      (FoodNet). The overall prevalence of acute diarrhoea in the 4 weeks before
      interview was 11%, giving a rate of 1.4 episodes of diarrhoea per person per
      year. The rate of diarrhoeal illness defined as a diarrhoeal episode lasting
      longer than 1 day or which resulted in significant impairment of daily activities
      was 0.7 per person per year. It can be concluded that acute diarrhoea is common
      and represents a significant burden of illness in the United States. Our data on
      self-reported diarrhoea, when generalized to the entire nation, suggests 375
      million episodes of acute diarrhoea each year in the United States. Many of these
      episodes are mild. However, our data also indicate that there are approximately
      200 million episodes of diarrhoeal illness each year in the United States.

PMID- 12211602
TI  - Detection of four Borrelia burgdorferi genospecies and first report of human
      granulocytic ehrlichiosis agent in Ixodes ricinus ticks collected in central
      Italy.
AB  - The presence of Borrelia burgdorferi s.l. and of Ehrlichia phagocytophila group
      was sought by PCR in Ixodes ricinus collected in a protected area of central
      Italy. Nymphs (n = 1475, gathered in 295 pools of 5 nymphs each) and adult ticks
      (n = 28) were examined. B. burgdorferi s.l. was detected in 13.8% of the nymph
      pools; of these, 63.4% were infected by B. valaisiana, 26.8% by B. afzelii, 7.3%
      by B. garinii, and 2.5% by B. burgdorferi s.s. Only a single adult male tick
      proved to host B. afzelii. The agent of human granulocytic ehrlichiosis (HGE) was
      detected in 2.7% of the nymph pools. Two HGE agent-positive nymph pools were also
      found to be positive for B. garinii and for B. afzelii, respectively. This is the
      first report from central Italy of the finding of the HGE agent in ticks.

PMID- 12211603
TI  - Contribution of RSV to bronchiolitis and pneumonia-associated hospitalizations in
      English children, April 1995-March 1998.
AB  - Estimates of the number of hospitalizations attributable to specific pathogens
      are required to predict the potential impact of vaccination. All hospital
      admissions for lower respiratory tract infection (LRI) in children < 5 years in
      England in 1995-8 were reviewed. Most admissions (76.8%) were not associated with
      specific organisms. Seasonality in pathogens that cause bronchiolitis and
      pneumonia was used to predict the proportion of cases with unspecified aetiology
      attributable to different organisms using multiple linear regression. Of 12,298
      admissions for LRI, 17.5% were due to RSV infection. An estimated 74.8% (95% CI,
      72.0-77.7%) of 'unspecified bronchiolitis' admissions and 16.3% (95% CI, 13.7
      18.8%) of unspecified pneumonia' admissions were RSV related. The total mean
      annual incidence of hospital admissions attributable to RSV is 28.3/1000 children
      < 1 year of age, and 1.3/1000 children 1-4 years old. The greater burden of RSV
      infection than indicated through discharge data is revealed through applying
      simple statistical methods.

PMID- 12211604
TI  - Efficacy of oryzalin and associated histological changes in Cryptosporidium
      infected neonatal rats.
AB  - This paper reports the anti-cryptosporidial effects of, and concomitant
      amelioration of the histological changes in the gut of neonatal rats with
      intestinal cryptosporidiosis treated with the dinitroaniline, oryzalin. The ED50
      was determined to be 7 mg/kg using twice daily doses administered for 3
      consecutive days. A maximum inhibition of 85.5% was achieved at 25 mg/kg and this
      inhibition remained constant despite increasing the oryzalin dose to 200 mg/kg.
      Cryptosporidiosis significantly decreased the intestinal villus/crypt (VC) ratio
      by approximately 50% (duodenum = 2.3, jejunum = 2.5 and ileum = 1.7) when
      compared to uninfected untreated controls (duodenum = 4.3, jejunum = 5.9 and
      ileum = 4.5). Treatment with oryzalin doubled the VC ratio in the duodenum,
      jejunum and ileum following doses of 5 mg, 50 mg and 200 mg/kg respectively.
      Oryzalin concentrations in the small intestine contents and plasma were
      determined, using HPLC, at 0.5, 1 and 2 h after dosing. The much greater dose
      required to return VC ratios to normal in the ileum (200 mg/kg) compared to the
      duodenum (6.25 mg/kg) appeared to reflect the decreased concentration of the drug
      in the distal small intestine. Concentrations of oryzalin equivalent to the in
      vitro IC50 were maintained for 2 h in the first half of the small intestine
      following a single dose of 100 mg/kg.

PMID- 12211605
TI  - Potential remedy against Echinococcus multilocularis in wild red foxes using
      baits with anthelmintic distributed around fox breeding dens in Hokkaido, Japan.
AB  - The effect of bait-delivered anthelmintic to reduce the prevalence of
      Echinococcus multilocularis in wild red foxes was evaluated in Koshimizu, in the
      eastern part of Hokkaido, Japan. The study area (200 km2) was divided into baited
      and non-baited sections. The anthelmintic baits were distributed around fox den
      sites in the baited section every month for 13 months. After 1 year of the
      anthelmintic bait distribution, the prevalence of E. multilocularis in foxes,
      evaluated either by the parasite egg examination (from 27.1 to 5.6%) or
      coproantigen ELISA (from 59.6 to 29.7%), decreased in the baited section
      contrasting to that in the non-baited section (parasite egg: from 18.8 to 24.2%;
      ELISA: from 41.9 to 45.8%). The prevalence of E. multilocularis in grey red
      backed vole Clethrionomys rufocanus, caught around fox dens, born after bait
      distribution also decreased and was significantly lower than that in non-baited
      section. However, within the study periods, the coproantigen-positive rate in fox
      faeces sporadically increased, while egg-positive rate constantly decreased.
      Since coproantigen ELISA can detect pre-patent infection, this observation
      indicates that reinfection pressure in the baited section was still high even
      after the 13 months of anthelmintic bait distribution. Therefore, the bait
      distribution longer than our study period is required for the efficient control
      of E. multilocularis in wild red fox population.

PMID- 12211606
TI  - Specificity of PCR and in situ hybridization assays designed for detection of
      Marteilia sydneyi and M. refringens.
AB  - Primers and DNA probes designed for use in the specific detection of the
      paramyxean parasites Marteilia sydneyi and Marteilia refringens were tested for
      their potential to cross-react with closely related species in Polymerase Chain
      Reaction (PCR) and in situ hybridization. PCR primers and a DNA probe designed
      within the ITS1 rRNA of M. sydneyi were specific for M. sydneyi when compared
      with related species of Marteilia and Marteilioides. PCR primers designed within
      the 18S rRNA of M. refringens were specific in the detection of this species in
      PCR while a DNA probe (named Smart 2) designed on the same gene cross-reacted
      with M. sydneyi in tissue sections of Saccostrea glomerata as well as
      Marteilioides sp. infecting Striostrea mytiloides. Though not species specific,
      the Smart 2 probe provided a stronger signal in detection of all stages of M.
      sydneyi than the ITSI probe. The ITS probe is proposed for use as a confirmatory
      diagnostic tool for M. sydneyi.

PMID- 12211607
TI  - Pathological effects of Pseudodiplorchis americanus (Monogenea: Polystomatidae)
      on the lung epithelium of its host, Scaphiopus couchii.
AB  - Infection of the desert toad, Scaphiopus couchii, by the monogenean
      Pseudodiplorchis americanus involves 2 principal sites: post-invasion juveniles
      reside in the respiratory tract for 1 month before migrating to the urinary
      bladder where they reach sexual maturity and may live up to 4 years. While
      previous work has demonstrated the long-term impact on host condition of the
      blood-feeding adults, this study assesses pathological effects of the short-term
      pulmonary infection. Lung ultrastructure was compared in toads (i) maintained in
      captivity for 1 year without invasion, and (ii) experimentally infected with 50
      300 juveniles/host, equivalent to burdens in the wild, and examined 23-44 days
      p.i. Typically, the alveolar lining of S. couchii is composed of a single cell
      type with characteristics of both Type I and Type II pneumocytes. However,
      infected lung tissue exhibited an inflammatory reaction with epithelial cell
      vacuolation, interstitial oedema, and an increase of alveolar exudate, leucocytes
      and fibrous tissue. Accompanying a post-infection increase in host immune cells
      in the lungs, there was evidence of reciprocal tegumental damage to the
      parasites. Lung epithelium of toads free of infection for 1 year exhibited scar
      tissue representing a residual effect of past infection. The pathological
      consequences of P. americanus infection therefore have 2 components. Acute lung
      infection coincides with the host's brief activity season: impaired respiratory
      function could compromise feeding and accumulation of reserves and hence ability
      to survive following a 10 month period of hibernation. Additionally, adult toads
      are normally exposed annually to re-infection and may accumulate chronic lung
      damage with extended effects on host survival.

PMID- 12211608
TI  - Expression of the filarial nematode phosphorylcholine-containing glycoprotein,
      ES62, is stage specific.
AB  - ES62, an immunomodulatory phosphorylcholine-containing glycoprotein secreted by
      the rodent filarial nematode Acanthocheilonema viteae, has previously been shown
      to be produced by L4 larvae and adult worms only. However, homologous sequences
      to ES62 have recently been found in L1 and L3 cDNA libraries of certain human
      filarial nematodes. Therefore, the various stages of A. viteae were re-examined
      and it was again found that only the post-L3 stages secreted ES62. Synthesis but
      not secretion by earlier stages was ruled out by examination of the protein
      content of whole worm extracts and by immunoelectron microscopy. However,
      examination by PCR of the mRNA for ES62 revealed that it was found in the L1 and
      L3 larvae. This may explain why homologous sequences to ES62 have been found in
      Brugia malayi and Onchocerca volvulus larval cDNA libraries. It also suggests
      that filarial nematodes, in general, may secrete ES62. To obtain evidence for
      this, we investigated production by Brugia pahangi, a close relation of B.
      malayi. We found that ES62 was indeed secreted but, as with A. viteae, only by
      the post-L3 stages, although again the mRNA for ES62 could be detected in the
      earlier stages. Overall our results suggest that production of ES62 is not
      species specific, that it is indeed stage specific, and that this may be due to
      post-transcriptional control of expression.

PMID- 12211609
TI  - Effects of phytohormones on the surfaces of plant-parasitic nematodes.
AB  - The direct effects of phytohormones (auxin and kinetin) and root diffusates on
      the surface lipophilicity of the plant parasitic nematodes Globodera
      rostochiensis and Meloidogyne incognita were investigated. The fluorescent lipid
      probe AF18 (5-N(octodecanoyl) aminofluorescein) was used to detect surface
      changes. Root diffusates increased AF18 uptake by G. rostochiensis while it had
      no effect on M. incognita. Kinetin and auxin decreased AF18 uptake in G.
      rostochiensis, while they had the opposite effect on M. incognita. Auxin/kinetin
      ratio was also found to be important in triggering the surface changes,
      especially at high concentrations. Whether plant nematodes have auxin and/or
      kinetin binding proteins is discussed as well as the mechanism behind the surface
      lipophilicity changes due to root diffusates and phytohormones.

PMID- 12211610
TI  - Characterization of Meloidogyne javanica surface coat with antibodies and their
      effect on nematode behaviour.
AB  - The surface coat of the 2nd-stage juveniles (J2) of plant-parasitic nematodes is
      considered to be involved in interactions with microorganisms in the soil and
      rhizosphere, as well as with the host plant. Characterization of surface antigens
      might be important in the development of new nematode control strategies. In this
      study, polyclonal and monoclonal antibodies raised against Meloidogyne javanica,
      M. incognita and other plant-parasitic nematodes were tested for their binding to
      the surface coat and secreted-excreted products of M. javanica. Some of the
      monoclonal and polyclonal antibodies raised against M. incognita showed cross
      reactivity with the surface coat of M. javanica. Western blot analysis of M.
      javanica surface coat extracts revealed labelling of several polypeptides with a
      48 kDa main band for the polyclonal antibody IACR-PC Mi 373, and a 55 kDa main
      band for PC Mj E2. Further characterization of the antigens recognized by the
      polyclonal antibody PC Mj E2, in planta, showed that they were present in the
      parasitic stages J2 and J3 and that the surface coat was shed during root
      penetration. The hypodermis of the infective juveniles was labelled by PC Mj E2
      and the monoclonal antibody IACR-Misec 3F.4, suggesting that these surface
      antigens are produced in the hypodermis. Nematode behaviour was affected by all
      the antibodies that bound to the surface coat of the pre-parasitic J2, and we
      demonstrated that the movement pattern of the M. javanica J2 was affected by
      these antibodies. Continuous binding of the antibodies to the M. javanica surface
      inhibited the infection of Arabidopsis thaliana roots on agar plates.

PMID- 12211611
TI  - Altered host behaviour: manipulation or energy depletion in tapeworm-infected
      copepods?
AB  - Parasites are able to influence intermediate hosts in a way that optimizes their
      growth and transmission to the next host. Macrocyclops albidus (Copepoda) suffer
      from a reduced escaping ability and an increased level of general activity, when
      infected with Schistocephalus solidus (Cestoda). This facilitates predation by
      the subsequent host, the three-spined stickleback. However, instead of adaptive
      host manipulation by the tapeworm, the altered copepod behaviour might be
      explained more simply as a constraint of the infection. Energy depletion could
      lead to decreased muscle performance and increased food searching activity.
      Furthermore, resource allocation among host tissues might change after infection.
      We therefore analysed the amount of storage lipids and muscle tissue before and
      after experimental infection. To determine the amount of muscles, we developed a
      new polarization-microscopic technique. Irrespective of infection, lipids and
      muscles were predictors of copepod survival. However, we found no effect of the
      parasite infection on muscles or lipids, and no indication of a change in
      resource allocation between these tissues. Our study suggests that behavioural
      changes in infected copepods are mediated by a mechanism different from energy
      depletion or a re-allocation of resources between muscles and lipids. We rather
      propose that the tapeworms directly manipulate copepod behaviour.

PMID- 12211612
TI  - Reduced efficacy of the immune melanization response in mosquitoes infected by
      malaria parasites.
AB  - Although the mosquito vectors of malaria have an effective immune system capable
      of encapsulating many foreign particles, they rarely encapsulate malaria
      parasites in natural populations. A possible reason for this apparent paradox is
      that infection by malaria reduces the capability of the mosquito to mount an
      effective immune response. To investigate this possibility, we blood-fed Aedes
      aegypti mosquitoes on an uninfected chicken or on one infected with Plasmodium
      gallinaceum, and compared the proportions of the infected and uninfected
      mosquitoes that melanized a negatively charged Sephadex bead injected into the
      thorax 1, 2 and 4 days after blood-feeding. About 40% of the uninfected
      mosquitoes, but less than 25% of the infected ones, melanized the bead. The
      difference between infected and uninfected mosquitoes was most obvious 1 day
      after infection (at the parasite's ookinete stage), while the difference
      diminished during the early oocyst stage (2 days after infection) and disappeared
      at the later oocyst stage (4 days after infection). These results suggest that
      the parasite can either actively suppress its vector's immune response or that it
      modifies the blood of its chicken host in away that reduces the efficacy of the
      mosquito's immune system. In either case, the reduction of immunocompetence can
      have important consequences for malaria control, in particular for the current
      effort being invested into the genetic manipulation of mosquitoes.

PMID- 12211613
TI  - The phylogeography of Asian Schistosoma (Trematoda: Schistosomatidae).
AB  - Partial (DNA) sequences are presented for 2 nuclear (18S and 28S rRNA genes) and
      2 mitochondrial (12S rRNA and ND1 genes) loci for 5 species belonging to the
      Schistosoma japonicum, S. sinensium and S. indicum groups of Asian Schistosoma.
      Fresh field isolates were collected and cultured for the following taxa: S.
      incognitum (S. indicum group, central Thailand), S. mekongi (S. japonicum group,
      southern Laos), S. ovuncatum (S. sinensium group, northern Thailand), S. spindale
      (S. indicum group, northeast Thailand and central Thailand isolates) and S.
      sinensium (S. sinensium group, Sichuan Province, China). This represents the
      first published DNA sequence data for S. ovuncatum and for S. sinensium s.s. from
      the type locality in China. The paper also presents the first sequence data at
      the above loci for S. incognitum (except for the 28S sequences) and S. sinensium.
      Congruence was observed between the phylogenies estimated for each locus,
      although the relationships of S. incognitum were not so well resolved. Fitch
      Margoliash, maximum likelihood (M/L) and maximum parsimony methods were used to
      estimate the phylogenies and the agreement between them was similar to that
      observed between loci. The ML tree was considered to best represent the data and
      additional 28S sequences (taken from the GenBank), for S. haematobium, S.
      japonicum, S. mansoni and Orientobilharzia turkestanicum, were used to construct
      an overall phylogeny. The S. indicum group taxa showed considerable divergence
      from the other Asian species and closest affinity with the African group. S.
      ovuncatum and S. sinensium appeared as sister taxa but their status as sibling
      species remained supported. The findings are discussed in the context of
      phylogeographical hypotheses for the origin of Schistosoma. An Asian origin for
      Schistosoma is also considered.

PMID- 12211614
TI  - Trends in the occurrence, determinants, and consequences of multiple births.
AB  - After a substantial decrease in the middle of the 20th century, multiple
      pregnancy rates have increased in many Western countries. Between the mid-1970s
      and 1998, the rate of twin pregnancies increased by 50% to 60% in England and
      Wales, France, and the United States. The rates of triplet or higher-order
      multiple pregnancies increased by 310% in France, 430% in England and Wales, and
      696% in the United States. One fourth to one third of the increase in twin or
      triplet pregnancies are attributable to a contemporaneous increase in maternal
      age. Furthermore, in countries with high occurrence of multiple births, 30% to
      50% of twin pregnancies and at least 75% of triplet pregnancies occur after
      infertility treatment. The impact of the increase in multiple births on preterm
      delivery rates in the overall population is mainly attributable to twin
      pregnancies. In Canada, France, and the United States, an increase in preterm
      births among multiples contributed almost as much as the increase in occurrence
      of multiple births to the increase or stabilization of the overall rates of
      preterm delivery observed in these countries.

PMID- 12211615
TI  - Obstetric intervention, stillbirth, and preterm birth.
AB  - Despite widespread recognition that preventing preterm birth is the most
      important perinatal challenge facing industrialized countries, preterm birth has
      increased steadily in recent years. This article examines the relation between
      trends in preterm birth, preterm labor induction/cesarean delivery, stillbirth,
      and infant mortality. The recent rise in preterm birth in the United States and
      Canada has been mainly due to increases in mild preterm birth (34-36 weeks). Live
      births at 34 to 36 weeks' gestation have increased largely as a consequence of
      increases in preterm induction and preterm cesarean delivery among women at high
      risk for adverse pregnancy outcomes. Increased obstetric intervention at 34 to 36
      weeks' gestation appears to have led to larger-than-expected temporal declines in
      stillbirth rates at this gestation. Infant mortality rates have declined overall
      and also among live births at 34 to 36 weeks' gestation. Obstetric intervention
      at preterm gestation, when indicated, can prevent stillbirth and reduce infant
      morbidity and mortality despite the increasing rates of preterm delivery.

PMID- 12211616
TI  - Trends in fetal growth among singleton gestations in the United States and
      Canada, 1985 through 1998.
AB  - We examined trends in fetal growth among singleton live births in the United
      States and Canada. The data files (n = 48,637,680; 16.6% blacks) for US births,
      and the Canadian Birth Database of Statistics Canada (n = 3,167,702) for Canadian
      births were used. Trends were assessed between 1985-86 and 1997-98 with reference
      to mean birthweight, birthweight-for-gestational-age z-score, and proportions
      delivered low birthweight (< 2,500 g), small for gestational age (SGA:
      birthweight < 10th centile for gestational age) and large for gestational age
      (LGA: birthweight > 90th centile). The term "mean birth weight" increased in the
      US and Canada between 1985 and 1998, as have the mean z-score. Rates of term SGA
      births declined among US (11% among whites and 12% among blacks) and Canadian
      births (27%). Preterm SGA births increased by 3% and 17%, respectively, among US
      whites and blacks, but declined by 11% among Canadian births. Further, term LGA
      births increased in the US (5% among whites and 9% among blacks) and Canada
      (24%). Preterm LGA births declined by 13%, 25%, and 14% among US whites and
      blacks, and Canadian births, respectively. These findings suggest that US and
      Canadian babies are getting bigger. The role of preterm obstetrical induction and
      preterm cesarean delivery are likely to have influenced these trends.

PMID- 12211617
TI  - Trends in fetal and infant deaths caused by congenital anomalies.
AB  - Understanding the causes that underlie the recent dramatic declines in infant
      deaths caused by congenital anomalies requires an appreciation of trends in cause
      specific infant mortality, and especially trends in gestational age-specific and
      cause-specific fetal mortality. This article examines temporal changes in
      gestational age-specific and cause-of-death-specific fetal mortality rates in
      Canada, congenital anomaly-related infant mortality rates in Canada, England and
      Wales, and the United States, and cause-of-death-specific infant mortality rates
      in Canada and the United States. Fetal deaths caused by congenital anomalies at
      very early gestation (20-25 weeks) have increased dramatically in recent years,
      while fetal and infant deaths at later gestations have declined. Prenatal
      diagnosis and selective termination of pregnancies affected by congenital
      anomalies appears to be the major factor responsible for the accelerated decline
      in infant deaths. Further declines in overall infant mortality in industrialized
      countries can be expected as a result of an increasing uptake of prenatal
      diagnosis.

PMID- 12211618
TI  - Trends in neural tube defect prevalence, folic acid fortification, and vitamin
      supplement use.
AB  - In this review, the authors analyze international trends in rates of neural tube
      defects (NTDs) during the past three decades. Population-based data sources
      include the Metropolitan Atlanta Congenital Defects Program and other US birth
      defects surveillance programs in the National Birth Defects Prevention Network,
      the International Clearinghouse for Birth Defects Monitoring Systems, and US and
      Canadian vital records. To analyze trends in vitamin consumption, we review data
      from the US National Health and Nutrition Examination Surveys and international
      surveys of multivitamin use. We discuss the role of factors associated with
      historic and continuing declines in NTD rates in most countries. These factors
      include the introduction and increased utilization of prenatal diagnosis,
      recommendations for multivitamin use in women of childbearing age, and population
      wide increases in blood folate levels that have occurred since food fortification
      was mandated. We also discuss research needs for further NTD prevention. This is
      a US government work. There are no restrictions on its use.

PMID- 12211619
TI  - Trends in smoking and overweight during pregnancy: prevalence, risks of pregnancy
      complications, and adverse pregnancy outcomes.
AB  - The prevalence of smoking during pregnancy is decreasing in some, but not all,
      developed countries, as the prevalence of overweight is increasing rapidly in
      most countries. During pregnancy, smoking increases the risk of placental
      abruption, but reduces the risk of preeclampsia, while overweight increases the
      risks of gestational diabetes, preeclampsia, and cesarean delivery. Both smoking
      and overweight are associated with dose-dependent increases in risks of
      stillbirth and very preterm birth (< 32 weeks). From a public health perspective,
      smoking and overweight today probably represent the most important modifiable
      risk factors for pregnancy complications and adverse pregnancy outcomes.

PMID- 12211620
TI  - Population trends in sudden infant death syndrome.
AB  - This review documents and assesses recent trends in sudden infant death syndrome.
      We review medical literature, Internet resources, and national governmental data.
      A striking reduction in SIDS incidence of more than 50% has been observed in
      various countries after interventions, particularly during the early 1990s, to
      reduce the prevalence of prone infant sleeping. A reduction in postneonatal
      mortality has accompanied these lower rates. Evaluation studies from several
      countries indicate that the SIDS rate drop is largely attributable to a decline
      in the proportion of babies sleeping prone. Within countries, the SIDS rate
      decline has not occurred to the same extent for different ethnic and socio
      economic groups. Future public health activities must aim to address this issue.
      In the post-intervention era, the relative importance of the risk factors of side
      compared to supine sleeping and soft bedding near the infant's airway have become
      more evident. Recent death scene data indicate that a substantial proportion of
      the remaining SIDS deaths could be avoided by supine sleeping and by providing a
      safe sleeping environment for all infants.

PMID- 12211621
TI  - The effect of gestational age errors and their correction in interpreting
      population trends in fetal growth and gestational age-specific mortality.
AB  - In perinatal research and clinical practice, gestational age is a crucial
      variable for measuring fetal "growth" (birth weight for gestational age) and for
      estimating the risk of mortality and morbidity. Yet, reported gestational age
      values are affected by random and systematic errors. This article reviews methods
      for detecting and correcting errors in gestational age and compares the effects
      of these methods on fetal growth standards and on the use of population-based
      data in analysis of trends in gestational-age specific infant mortality.

PMID- 12211622
TI  - Contribution of genetic polymorphisms in ethanol-metabolizing enzymes to problem
      drinking behavior in middle-aged Japanese men.
AB  - Among ethanol-metabolizing enzymes, the ALDH2*2 allele, ADH2*2 allele, and c2
      allele of the cytochrome P450-2E1 (CYP2E1) gene are unique to Orientals. This
      prompted us to analyze their contribution to drinking behavior in 322 middle-aged
      Japanese men. The ALDH2*2 allele, detected in nearly half of the subjects, showed
      an overwhelming protective effect against a high level of alcohol consumption and
      problem drinking behavior, as determined by the Kurihama Alcoholism Screening
      Test (KAST). The ADH2*2 allele, in 95% of the subjects, exhibited an additive
      suppressive effect on alcohol consumption, whereas the c2 allele of CYP2E1, in
      40% of the subjects, was associated with greater alcohol consumption. Problem
      drinkers showing a KAST score of 2.0 or higher were frequent among the few
      subjects with the ADH2*1/1 genotype, but not in the large number of subjects
      having the c2 allele of CYP2E1. These findings may explain, at least in part, why
      in Japan the number of alcoholic patients is small relative to the number of
      heavy drinkers.

PMID- 12211623
TI  - Genetic and environmental influences on the development of intelligence.
AB  - Measures of intelligence were collected in 209 twin pairs at 5, 7, 10, and 12
      years of age, as part of a longitudinal project on intelligence, brain function,
      and behavioral problems. Intelligence was measured at 5, 7, and 10 years of age
      with the RAKIT, a well-known Dutch intelligence test, consisting of 6 subscales.
      At 12 years of age, the complete WISC-R was administered (12 subscales). Both
      intelligence tests resulted in a measure of full-scale IQ (FSIQ). Participation
      rate is around 93% at age 12. Correlation coefficients over time are high: (r(5
      7) = .65; r(5-10) = .65; r(5-12) = .64; r(7-10) = .72; r(7-12) = .69 and r(10-12)
      = .78). Genetic analyses show significant heritabilities at all ages, with the
      expected increase of genetic influences and decrease of shared environmental
      influences over the years. Genetic influences seem to be the main driving force
      behind continuity in general cognitive ability, represented by a common factor
      influencing FSIQ at all ages. Shared environmental influences are responsible for
      stability as well as change in the development of cognitive abilities,
      represented by a common factor influencing FSIQ at all ages and age-specific
      influences, respectively.

PMID- 12211624
TI  - The heritability of gender identity disorder in a child and adolescent twin
      sample.
AB  - The heritability and prevalence of the gender identity disorder (GID) was
      examined, as well as its comorbidity with separation anxiety and depression, in a
      nonretrospective study of child and adolescent twins. The parents of 314 twins
      (ages 4-17 years; 96 monozygotic pairs [MZ] and 61 dizygotic [DZ] pairs)
      completed the Coolidge Personality and Neuropsychological Inventory (CPNI)
      containing a six-item DSM-IV-based GID scale. Prevalence of clinically
      significant GID symptomatology in the twin sample was estimated to be 2.3%.
      Univariate model fitting analyses were conducted using an ordinal transformation
      of the GID scale. The model that best described the data included a significant
      additive genetic component accounting for 62% of the variance and a nonshared
      environmental component accounting for the remaining 38% of the variance. Results
      suggested no heterogeneity in the parameter estimates resulting from age. The
      correlation between GID and depression was modest, but significant (r = .20; P <
      .05), whereas the correlation between GID and separation anxiety was
      nonsignificant (P > .05). Overall, the results support the hypothesis that there
      is a strong heritable component to GID. The findings may also imply that gender
      identity may be much less a matter of choice and much more a matter of biology.

PMID- 12211625
TI  - Prenatal cocaine exposure alters maternal retrieval behavior in mice.
AB  - Previous studies have demonstrated alterations in maternal retrieval behavior as
      a result of direct cocaine exposure. To establish the influence of prenatal
      cocaine exposure on pup retrieval, we exposed pups of three F1 genotypes by
      injecting their mothers (all C57BL/10J strain) with 20 mg/kg cocaine
      hydrochloride or saline subcutaneously on gestation days 7 to 17. When those pups
      became adults, control and exposed females were mated with males of the same
      genotype and tested for pup retrieval on postpartum days 4 and 5. Because
      ultrasonic calls are known to be elicitors of maternal retrieval behavior, the
      rate of ultrasonic calling was measured. Prenatal cocaine exposure exerted a
      significant effect upon retrieval latency on day 4. No relationship was found
      between genotype and retrieval latency.

PMID- 12211626
TI  - The effects of cold, rotation, and genotype on the production of ultrasonic calls
      in infant mice.
AB  - There has been a revival of interest recently in the ultrasonic calls of infant
      rodents as investigators are using them to assess neurobehavioral development and
      animal models of anxiety. We compared the rates of ultrasonic calling of infant
      mice of two genotypes in two situations, cold and rotation. The subjects of study
      were 169 mouse pups from 29 litters and of two F1 genotypes, C57BL/10J x DBA/2J
      and C57BL/10J x SJL/J. Half of each litter was recorded in a cool situation for
      20 seconds and the other half was recorded while rotating at 10 rpm for 20
      seconds. All pups were recorded on days of age 2 to 8. Rotation elicited calling
      at about twice the rate as cool temperature on each day of age and on average
      across days; situation (cold or rotation) accounted for over 50% of the variation
      between litters. Genotype also altered call rate, and on some days situation and
      genotype interacted. In studies of neurobehavioral development and the effects of
      pharmacological agents on infant mice, it is particularly important to understand
      the roles of the stimuli and genotypes employed.

PMID- 12211627
TI  - Genetic control of germline sexual dimorphism in Drosophila.
AB  - Females produce eggs and males produce sperm. Work in Drosophila is helping to
      elucidate how this sex-specific germline differentiation is genetically encoded.
      While important details remain somewhat controversial, it is clear that signals
      generated by somatic cells, probably in the embryonic gonads, are required as
      extrinsic factors for germline sex determination. It is equally clear that the
      sex chromosome karyotype of the germ cell is an intrinsic factor for germline sex
      determination. There is also extensive somatic signaling required for
      differentiation of germline cells in the adult gonads. Mismatched germline and
      somatic line sexual identities place germ cells in an inappropriate signaling
      milieu, which results in either failed maintenance of germline stems cells when
      female germ cells are in a male soma or overproliferation of germline cells when
      male germ cells are in a female soma. The well-studied somatic sex determination
      genes including transformer, transformer-2, and doublesex are clearly involved in
      the nonautonomous signaling from somatic cells, while the autonomous functions of
      genes including ovo, ovarian tumor, and Sex-lethal are involved in the germline.
      The integration of these two pathways is not yet clear.

PMID- 12211628
TI  - Functional diversity of axonemal dyneins as studied in Chlamydomonas mutants.
AB  - Cilia and flagella of most organisms are equipped with two kinds of motor protein
      complex, the inner and outer dynein arms. The two arms were previously thought to
      be similar to each other, but recent studies using Chlamydomonas mutants indicate
      that they differ significantly in subunit structure and arrangement within the
      axoneme. For example, whereas the outer dynein arm exists as a single protein
      complex containing three heavy chains, the inner dynein arm comprises seven
      different subspecies each containing one or two discrete heavy chains.
      Furthermore, the two kinds of arms appear to differ in function also. Most
      strikingly, our studies suggest that inner-arm dynein, but not outer-arm dynein,
      is under the control of the central pair microtubules and radial spokes. The
      axoneme thus appears to be equipped with two rather distinct systems for beating:
      one involving inner-arm dyneins, the central pair and radial spokes, and the
      other involving outer-arm dynein alone.

PMID- 12211629
TI  - Genetic alterations in ovarian cancer cells that might account for sensitivity to
      chemotherapy in patients.
AB  - The cellular response to anticancer agent treatments is determined by many
      factors that could be altered in tumor cells. The induction of apoptosis of
      cancer cells is thought to be important for the overall response of these cells.
      Despite the introduction of new and potent anticancer agents, the survival rate
      for patients with ovarian cancer remains poor. In general ovarian cancer cells
      present a poor propensity to undergo apoptosis, which could be one of the reasons
      for this relatively poor response observed in the clinic. Induction of apoptosis
      is the result of activation and repression of pro- and antiapoptotic genes, which
      are regulated by complex mechanisms. Many cancer cells activate a "survival"
      program to escape disruption and allow propagation. In this review we have
      analyzed the role of genetic alterations observed in ovarian cancer cells in
      determining cellular response to drug treatment.

PMID- 12211630
TI  - Conventional and nonconventional roles of the nucleolus.
AB  - As the most prominent of subnuclear structures, the nucleolus has a well
      established role in ribosomal subunit assembly. Additional nucleolar functions,
      not related to ribosome biogenesis, have been discovered within the last decade.
      Built around multiple copies of the genes for preribosomal RNA (rDNA), nucleolar
      structure is largely dependent on the process of ribosome assembly. The nucleolus
      is disassembled during mitosis at which time preribosomal RNA transcription and
      processing are suppressed; it is reassembled at the end of mitosis in part from
      components preserved from the previous cell cycle. Expression of preribosomal RNA
      (pre-rRNA) is regulated by the silencing of individual rDNA genes via alterations
      in chromatin structure or by controlling RNA polymerase I initiation complex
      formation. Preribosomal RNA processing and posttranscriptional modifications are
      guided by a multitude of small nucleolar RNAs. Nearly completed ribosomal
      subunits are exported to the cytoplasm by an established nuclear export system
      with the aid of specialized adapter molecules. Some preribosomal and nucleolar
      components are transiently localized in Cajal bodies, presumably for modification
      or assembly. The nonconventional functions of nucleolus include roles in viral
      infections, nuclear export, sequestration of regulatory molecules, modification
      of small RNAs, RNP assembly, and control of aging, although some of these
      functions are not well established. Additional progress in defining the
      mechanisms of each step in ribosome biogenesis as well as clarification of the
      precise role of the nucleolus in nonconventional activities is expected in the
      next decade.

PMID- 12211631
TI  - Gene silencing.
AB  - Gene silencing has evolved in a broad range of organisms probably as defense
      mechanisms against invasive nucleic acids. Two major strategies are utilized.
      Transcriptional gene silencing (TGS) acts to prevent RNA synthesis and
      posttranscriptional gene silencing (PTGS) acts to degrade existing RNA. Although
      the final effects are similar, the mechanisms of TGS and PTGS are species
      specific. In most eukaryotes, gene silencing is associated with de novo DNA
      methylation. However, Caenorhabditis elegans shows an efficient PTGS-like
      mechanism but lacks a DNA methylation system. Additionally, key enzymes involved
      in plant and nematode PTGS, the cellular RNA-directed RNA polymerases, appear to
      be missing in Drosophila melanogaster. In this review, we discuss common features
      of TGS and PTGS that have been identified across species but for TGS we will
      concentrate only on methylation-mediated gene inactivation. This effort is
      complicated by the vague borders between gene silencing and normal gene
      regulation. Mechanisms that are involved in gene silencing are also used to
      regulate controlled expression of endogenous genes. To outline the general
      aspects, gene silencing will be defined as narrowly as possible. The intention
      behind this review is to stimulate discussion and we seek to facilitate this by
      introducing speculative concepts that could lead to some reappraisal of the
      literature.

PMID- 12211633
TI  - Pulmonary microbial infection in mice: comparison of different application
      methods and correlation of bacterial numbers and histopathology.
AB  - Many investigations have been performed in characterising experimental bacterial
      infections in the lung of mice using several pathogens. Robust experimental
      pulmonary infection models require a reproducible method of application with
      defined numbers of pathogens to the respiratory tract without contaminating
      extrapulmonary tissues. At the same time trauma due to the experimental procedure
      should be kept to a minimum. So far several routes of administration have been
      used but a systematic comparison of these methods is still missing. Here we
      provide a comprehensive evaluation of view controlled i.t. instillation,
      tracheotomy, intranasal application, blind instillation and aerosol infection. An
      infection dose of up to 5 x 10(4) bacteria (L. monocytogenes) was applied to a
      group of ten mice by each technique and the animals were killed after 1 h or 24h.
      The number of viable bacteria was estimated by plating homogenates of the lungs
      and spleens. In addition, pathological effects on lung tissue were examined by
      histology 24h after infection. The highest reproducibility was achieved after
      applying Listeria directly in the trachea under view or by tracheotomy. However,
      mice were severely affected in their vitality after tracheotomy. Thus, for
      topical application of bacterial suspension into the lung the view controlled
      i.t. instillation is most appropriate.

PMID- 12211632
TI  - Pulmonary inflammation in rats after intratracheal instillation of quartz,
      amorphous SiO2, carbon black, and coal dust and the influence of poly-2
      vinylpyridine-N-oxide (PVNO).
AB  - Effects of poly-2-vinylpyridine-N-oxide (PVNO) were investigated in numerous in
      vivo and in vitro studies published in the nineteen sixties and seventies. These
      studies showed that PVNO inhibited development of fibrosis from quartz dust and
      improved lung clearance of quartz after inhalation exposure. Ameliorating effects
      of PVNO were observed also for pulmonary damage from colloidal SiO2 and organic
      substances, and the fibrogenic inflammation caused by carrageenan. Although it is
      not proven that silicosis is a precondition for quartz-induced lung tumours, we
      investigated the hypothesis that PVNO could reduce the lung tumour risk from
      quartz in rats. A carcinogenicity study was therefore started in rats with the
      main focus on the quantitative relationships among pulmonary inflammation,
      fibrosis and neoplasia caused by intratracheal instillation of 3 mg quartz DQ 12
      with or without additional subcutaneous PVNO treatment. Other study groups were
      treated with multiple dust instillations, i.e. 30 instillations of 0.5 mg
      amorphous SiO2 at intervals of 2 weeks, 10 instillations of 0.5 mg of ultrafine
      carbon black or 1 mg coal at weekly intervals. The analyses of the
      bronchoalveolar lavage fluid (BALF) 9 months after start of the life-time study
      showed that the aim of producing similar levels of increased enzyme
      concentrations in the four groups treated with quartz/PVNO, amorphous SiO2,
      carbon black and coal was achieved. A 2.5- to 7.7-fold increase for lactate
      dehydrogenase (LDH), total protein, alkaline phosphatase and gamma-glutamyl
      transferase (gamma-GT) was found in these groups as compared to the control. In
      contrast, quartz treatment without PVNO increased the LDH level up to 24-fold and
      of total protein to 13-fold. However, the cell counts in the BALF were not so
      much different in all five groups, i.e. quartz without PVNO (leukocytes: 480.000,
      PMN: 190.000), quartz with PVNO (leukocytes: 300.000, PMN: 100.000), amorphous
      SiO2 (leukocytes: 570.000, PMN: 315.000), carbon black (leukocytes: 390.000, PMN:
      150.000) and coal (leukocytes: 200.000, PMN: 65.000). Histopathological
      investigations after four weeks and three months revealed that the used PVNO
      sample was active in the quartz and amorphous SiO2 groups and markedly reduced
      the incidences or severity of several pulmonary changes such as macrophage
      accumulation, inflammatory cell infiltration, interstitial fibrosis, bronchiolo
      alveolar hyperplasia, alveolar lipoproteinosis and amorphous SiO2 -induced
      granulomatous alveolitis/interstitial fibrotic granulomas. Also in the lung
      associated lymph nodes (LALN), PVNO treatment significantly reduced the incidence
      and severity of inflammation in both quartz and amorphous SiO2 groups as
      evidenced by the presence of well-circumscribed aggregates of intact particle
      laden macrophages without signs of degeneration and accompanying granulocytic
      infiltration and fibrosis. Immunological investigations at the 9 months timepoint
      on the in vitro production of reactive nitrogen (RNI) or oxygen (ROI)
      intermediates and tumour necrosis factor (TNF-alpha) from BALF-derived cells
      indicated a diminished responsiveness to LPS in all particle treatment groups. A
      diminished production of ROI was also found in the quartz, carbon black, and coal
      dust groups, respectively, as compared to the values seen in the quartz/PVNO- and
      amorphous SiO2 treated groups. Treatment with quartz plus PVNO restored the
      capability of the cells to respond to LPS as compared to the treatment with
      quartz alone. TNF-alpha production was diminished in the groups treated with
      quartz, carbon black, and coal dust alone whereas in the quartz/PVNO- and
      amorphous SiO2-treated groups an elevated TNF-alpha production was seen. These
      results led to the conclusion that only amorphous SiO2 did not affect the
      "normal" ability of the cells to respond to LPS and that PVNO protected the cells
      from a toxic effect of the quartz particles.

PMID- 12211634
TI  - Analysis of markers of exposure to polymeric methylene-diphenyl diisocyanate
      (pMDI) in rats: a comparison of dermal and inhalation routes of exposure.
AB  - Rats received polymeric methylenediphenyl-diisocyanate (pMDI) or a mixture of
      methylenediphenyl-4,4'-diamine (4,4'-MDA) and amino-di(aminophenylmethylene)
      benzene (3-core MDA) by single inhalation or dermal exposure. The ratio of 4,4'
      MDA and 3-core MDA used in this study mirrored that of 4,4'-MDI and 3-core MDI
      present in pMDI. The yields of the corresponding markers of exposure in
      hydrolyzed blood (Hb-adducts) and urine were determined. For the inhalation
      exposure, rats were acutely exposed for a duration of 6 h to 3.7 mg pMDI/m3 and
      2.7 mg MDA/m3, respectively. Furthermore, C x t products of approximately 1200 mg
      pMDI/m3 x h were examined, ranging from 3 h x 6.2 mg/m3, 1.5 h x 12.7 mg/m3, 45
      min x 25.1 mg/m3, and 23-min x 58.1 mg/m3. Additional groups of rats received
      equimolar doses of pMDI and MDA by epicutaneous exposure, i.e., 100 mg pMDI/kg
      bw, equivalent to approximately 50 mg 4,4'-MDI/kg bw and 34 mg 3-core MDI/kg bw
      or 79 mg MDA-mixture/kg bw, equivalent to 46 mg 4,4'-MDA/kg bw and 33 mg 3-core
      MDA/kg bw. The biomarkers measured in this study suggest that the kind and yield
      of biomarkers are dependent on the route of exposure and differ markedly for MDI
      and MDA. This isocyanate appears to undergo reactions specific to the site of
      first contact (e.g., formation of adducts, conjugates and/or polyureas),
      suggesting that these markers of 'total body burden' can neither predict the
      local dose at that site nor does it provide any means to identify the route
      receiving the most critical dose. Similarly, it appears that the formation of
      biomarkers is governed by reactions requiring an intact isocyanate group rather
      than hydrolysis. In contrast, for MDA this type of portal-of-entry specificity
      was not observed. Moreover, trace amounts of diamines available to dermal
      contact, with respect to the isocyanate, may cause false-positive readings. Thus,
      in spite of the recognized advantages of biomonitoring to identify cryptic
      exposures not readily detected by conventional analytical sampling procedures, in
      regard to pMDI this technique appears to be potentially biased to overestimate
      exposure, i.e., results obtained from integrating dosimeters of exposure need to
      be verified by adequate air monitoring.

PMID- 12211635
TI  - The results of the interference of nitrates and vitamin E in the metabolism in
      the connective tissue of rat's liver.
AB  - We examined 72 female Wistar rats which were divided into 6 groups. The animals
      were administered sodium nitrate (V), vitamin E or both compounds at the same
      time. In order to estimate the interference of nitrates in the presence of
      vitamin E with the metabolism of rat's liver, we determined the composition and
      the amount of glycosoaminoglycans (GAGs). It was stated that the total amount of
      GAGs increased in livers of all rats. Basing on all fractions of the examined
      GAGs it was determined that the most significant differences between individual
      groups appeared in the amount of heparane sulphate (HS). The results obtained
      confirmed the fact of the changes taking place in the picture of liver GAGs in
      the process of ageing of the examined animals. The results obtained, however,
      allowed to state the normalising influence of vitamin E on the quantitative
      composition of GAGs of rats which drank nitrates.

PMID- 12211636
TI  - Species- and sex-specific variations in binding of ochratoxin A by renal proteins
      in vitro.
AB  - The mycotoxin ochratoxin A (OTA) is a potent renal carcinogen in rodents and
      induces renal fibrosis in pigs. Furthermore, OTA has been associated with the
      development of renal tumors and nephropathies in humans. Large species- and sex
      differences are observed in sensitivity toward OTA-mediated toxicity and
      carcinogenicity, yet neither the mechanism(s) resulting in OTA toxicity nor the
      reasons for the observed species- and sex-specificities are known. This paper
      investigated variations in OTA handling viz binding to renal proteins which could
      possibly explain the observed differences in OTA susceptibility in vivo and in
      vitro. The results obtained via a modification of a standard receptor-binding
      assay demonstrated the presence of at least one homogeneous binding component in
      renal cortical homogenates from pig, mouse, rat and humans. This component was
      shown to bind OTA in a specific and saturable manner. A range of compounds
      selected for their affinity for steroid receptors and/or for various known
      organic anion transporters were employed in a competition assay to answer the
      question whether this homogenous OTA binding component represents a steroid-like
      receptor component or one of the known organic anion transporters of the kidney.
      Although many of the compounds were able to compete with OTA for protein-binding,
      the competition patterns displayed a distinct species specificity and did not
      correspond to the competition patterns associated with presently known organic
      anion transporters of the kidney in the mouse, rat or human. The data thus
      suggests the presence of a new organic anion transporter or more likely, a
      cytosolic binding component of unknown function with high affinity and capacity
      for OTA binding in humans, rats, mice and possibly pigs.

PMID- 12211637
TI  - Cloning of animals--perspectives for biomedical research.

PMID- 12211638
TI  - Stereology--benefits and pitfalls.

PMID- 12211639
TI  - Importance and impact of discovery pathology.

PMID- 12211640
TI  - Laser technologies in toxicopathology.

PMID- 12211641
TI  - Effect of d,l-ethionine administration on the histomorphology of canine
      pancreatic acinar and beta-cells.
AB  - d,l-Ethionine produces pancreatic exocrine necrosis and islet proliferation in
      hamsters and dogs. As a first step in examining whether induction of islet
      proliferation has therapeutic applications in animals with exhausted or destroyed
      insulin-producing beta-cells, we studied pancreatic pathological alterations
      after intravenous administration of d,l-ethionine in normal dogs.
      Histomorphological changes in pancreatic acinar cells and beta-cells were
      assessed in three groups of six clinically normal crossbred dogs administered d,l
      ethionine (100 mg/ kg) intravenously three times a week for two weeks. Six
      additional dogs served as untreated controls. Group I was euthanased and
      necropsied on day 15 (72 hours after the final dose of ethionine). Groups II and
      III were euthanased on days 29 and 43 respectively. Severe acinar destruction
      occurred resulting in significant (p < 0.001) shrinkage of the pancreas in all
      groups. Although there was variability in histomorphology within groups,
      pancreases of group I generally exhibited widespread loss of pancreatic acinar
      structure. Remaining acinar cells were difficult to discern from other cell types
      within lobules and were surrounded by infiltrates, predominantly of lymphocytes.
      Partial acinar cellular regeneration had occurred by day 29, but was still
      incomplete at day 43. Immunohistochemistry suggested that the effect of d,l
      ethionine administration on the histomorphology of beta-cells in the left lobe
      was minimal; however, morphometry demonstrated a significant (p < 0.05) increase
      in the number of individual beta-cells in groups II and III, and clusters of 2
      10, 10-20 and 20+ cells in Group II. It is probable that the apparent increase in
      the number of individual and other beta-cell arrangements observed in some groups
      resulted primarily from alterations in the exocrine tissue, although some beta
      cell hyperplasia cannot be excluded completely.

PMID- 12211642
TI  - Experimental renal failure and iron overload: a histomorphometric study in the
      alveolar bone of rats.
AB  - Renal failure is a serious disease of a relatively high incidence, which among
      other lesions, causes bone alterations. These patients frequently suffer from
      anemia that is generally treated with iron. Given that iron overload inhibits
      bone formation, our aim was to evaluate the effect of iron on the interradicular
      bone of animals with experimental renal failure. Acute renal failure was induced
      in male rats by 5/6 nephrectomy. The animals were subjected to iron overload in
      the form of daily intraperitoneal injections of 88 mg/kg body weight of iron
      dextran over a period of 16 days. Tetracyclines were injected intraperitoneally
      14 days apart to evaluate dynamic parameters of bone. Serum urea and creatinine
      levels were evaluated immediately before the animals were killed on day 30.
      Static and dynamic histomorphometric measurements were performed. The data
      indicate that the iron overload modified the response of the renal failure
      animals which showed decreased interradicular bone volume and adynamic bone
      disease, characterized by reduced cell activity. These results should be taken
      into account when renal failure patients treated with iron must undergo dental
      treatments that depend on bone forming activity for their success.

PMID- 12211643
TI  - 5-Azacytidine (5AzC)-induced histopathological changes in the central nervous
      system of rat fetuses.
AB  - 5-Azacytidine (5AzC) is a cytidine analogue which possesses nitrogen atom instead
      of carbon atom at the position 5 of the pyrimidine ring. In this study, detailed
      histopathological changes were sequentially examined in the rat fetal brain
      obtained from dams treated with 5AzC (10 mg/kg) on day 13 of gestation (GD13). At
      6 hours after treatment (HAT), a prominent accumulation of neuroepithelial cells
      showing pleomorphic mitotic figures were observed in the telencephalic wall. The
      mitosis-index peaked at 6 HAT, and decreased thereafter. Neuroepithelial cells
      positive for nick end labeling (TUNEL) method, which is widely used for the
      detection of apoptotic cells, prominently increased at 9 HAT, and the TUNEL-index
      peaked at 12 HAT. TUNEL-positive cells showed ultrastructural characteristics of
      apoptosis. At 24 HAT, the formation of rosette-like structures was observed in
      the fetal brain. From the results of the present study, it was evident that
      abnormal mitosis and neuronal apoptosis were induced in the rat fetal brain
      following 5AzC-administration to dams on GD13. In addition, it is suggested that
      5AzC-induced apoptosis might occur mainly in the post mitotic phase of cell
      cycle.

PMID- 12211644
TI  - Protective role of melatonin and a combination of vitamin C and vitamin E on lung
      toxicity induced by chlorpyrifos-ethyl in rats.
AB  - The ameliorating effects of melatonin and vitamin C plus vitamin E were examined
      histologically and biochemically in lung tissues in rats exposed to chlorpyriphos
      ethyl (CE). Experimental groups were as follows: Control group (C), CE treated
      group (CE), vitamin C plus vitamin E treated group (Vit), melatonin treated group
      (Mel), vitamin C plus vitamin E plus CE treated group (Vit + CE), and melatonin
      plus CE treated group (Mel + CE). Vitamin E and vitamin C were administered
      intramuscularly at the rates of 150 and 200 mg per kg body weight, respectively,
      in Vit and Vit + CE groups, once a day for 6 consecutive days. Melatonin was
      administered intramuscularly at the rate of 10 mg per kg body weight in Mel and
      Mel + CE groups, once a day for 6 consecutive days. At the end of the fifth day,
      the rats of CE, Vit + CE and Mel + CE groups were treated orally with CE
      dissolved in corn oil with two equal doses of 41 mg CE per kg body weight at zero
      and twenty-first hours. Tissue samples of lungs were taken by using appropriate
      techniques for biochemical and histological examinations under anesthesia at the
      twenty-fourth hours of CE administration, at the end of the sixth day of the
      experiment. In tissue homogenates, the level of thiobarbituric acid reactive
      substances (TBARS), antioxidant potential (AOP), and the activities of superoxide
      dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were
      determined. TBARS was significantly high (p < 0.05) in CE group compared to
      control group, while TBARS was found to significantly decrease (p < 0.05) with
      Vit and Mel groups compared to control. On the other hand, TBARS was seen to
      significantly decrease (p < 0.05) in both groups of Vit + CE and Mel + CE
      compared to CE group. In comparison with CE group, SOD activity was significantly
      high (p < 0.05) with the groups of Vit, Mel, Vit + CE and Mel + CE. GSH-Px
      activity was found to significantly decrease (p < 0.05) with CE group, compared
      with both C and Vit groups. AOP was significantly lower (p < 0.01) in CE group
      than C group. Although there was an increased AOP with Vit + CE and Mel + CE
      groups compared to CE group, the increase in AOP was only seen to be significant
      (p < 0.05) in Mel + CE group. In comparison with C group, AOP significantly (p <
      0.05) increased with Vit group. There was also a significant (p < 0.05) increase
      in AOP with Mel + CE group, compared with CE group. Additionally, AOP was
      significantly lower (p < 0.05) in Vit + CE group than Mel + CE group. Lungs were
      examined histologically at the end of sixth day. There were remarkable changes in
      the histomorphology of peribronchial and perivascular area in the lung of rats
      treated with CE. These were infiltration of mononuclear cells (such as
      lymphocytes, plasmocytes, macrophages), hyperplasia of type II pneumocyte, and
      thickened and increased connective tissue. Damage to the lung tissue such as
      increased inflammatory mononuclear cells in peribronchial and perivascular areas
      were more pronounced for the CE group than Vit + CE and Mel + CE groups in which
      these changes were higher than C, Vit and Mel groups. These results suggest that
      CE increases lipid peroxidation and decreases antioxidant enzymes activities and
      AOP due to increasing oxidative stress induced by CE, and high doses of vitamin C
      plus vitamin E and melatonin considerably reduce CE toxicity in lung tissues of
      rats.

PMID- 12211645
TI  - IFCC: primary reference procedures for the measurement of catalytic
      conccentrations of enzymes--the new concept.

PMID- 12211646
TI  - Allele frequency of the G-->T mutation of the col1A1 gene analyzed by an ARMS-PCR
      in osteoporotic subjects with femoral neck fractures.
AB  - The allele frequency of the G-->T mutation of COL1A1 gene (collagen type I alpha
      1 gene, GenBank accession n. AF017178) was analyzed by a newARMS-PCR method in
      240 osteoporotic subjects bearing a femoral neck fracture. The method is based on
      the amplification refractory mutation system-polymerase chain reaction (ARMS
      PCR). Normal and mutated alleles were detected by two PCRs, in which a common
      forward primer (positions 1307 to 1336 of the gene) and two reverse primers
      (positions 1566 to 1546), differing in the 3'-base (3'-C for the normal Sallele
      and 3'-A for the mutated sallele) are used. In the SS condition, amplification
      occurs only in one of the two PCRs, and in the ss condition only in the other. In
      the Ss condition both reactions give a product. This ARMS-PCR method avoids the
      use of any restriction enzyme, as described by Grant and colleagues in a
      previously published method based on a mismatched reverse primer which introduced
      a restriction site in the T-substituted (s) allele and in a method recently
      proposed by Vinkanharju and co-workers. In a survey for COL1A1 polymorphism in
      240 osteoporotic subjects with femur fractures, here presented, a frequency of
      80.6% was found for the G allele and 19.4% for the T allele. There were 66.7%
      dominant SS subjects, 27.9% Ss heterozygotes and 5.4% ss recessive homozygotes.

PMID- 12211647
TI  - Vitamin supplementation normalizes total plasma homocysteine concentration but
      not plasma homocysteine redox status in patients with acute coronary syndromes
      and hyperhomocysteinemia.
AB  - Despite the growing evidence that elevated total homocysteine (tHcy) in plasma is
      a cardiovascular risk factor, the mechanism underlying the vascular injury is
      still unknown. Studies are difficult due to the fact that little is known about
      the formation of different homocysteine species in vivo. In the present study we
      have investigated the different fractions of tHcy in 21 patients with acute
      coronary syndromes and elevated concentration of plasma tHcy. A subgroup of the
      patients (n=16) was investigated before and after a 3 months study period with or
      without vitamin supplementation (folic acid 5 mg, pyridoxine 40 mg and
      cyanocobalamin 1 mg once daily). A major finding is that these patients had a
      lowered ratio (0.95%) between the concentration of reduced homocysteine (HcyH)
      and tHcy compared to controls (1.38%). A low ratio HcyH/tHcy in plasma in
      combination with elevated plasma tHcy concentrations might reflect increased
      oxidative activity or decreased reducing capacity in plasma from the patients.
      Another main finding in the present study is that, although vitamin
      supplementation of these patients normalized plasma tHcy, the ratio between HcyH
      and tHcy did not normalize. Since substantial evidence indicates that progression
      of arteriosclerosis is related to enhanced oxidant activity, the premature
      vascular disease associated with increased plasma tHcy concentration might be due
      to increased oxidative activity and the elevated plasma tHcy concentration may
      only reflect the increased oxidative stress.

PMID- 12211648
TI  - Mutation analysis of the MPZ and PMP22 genes in Croatian patients.
AB  - We used single-strand conformation polymorphism analysis for mutational screening
      in two candidate genes, MPZ and PMP22, which have an important role in the
      pathogenesis of Charcot-Marie-Tooth disease (CMT) and related peripheral
      neuropathies. A novel Ser8Ser polymorphism was found in exon 1 of the MPZ gene in
      two heterozygous subjects, in a father with mild CMT2 phenotype and his daughter
      with normal clinical data. Thr118Met polymorphism was found in exon 5 of the
      PMP22 gene. The patient heterozygous for 118Met allele had CMT1 disease. We can
      conclude that the occurrence of the 118Met allele does not usually cause CMT1 and
      that it is not a clinically relevant disease marker.

PMID- 12211649
TI  - Dynamic equilibrium between protein S and C4b binding protein is important for
      accurate determination of free protein S antigen.
AB  - Protein S in circulation is in a dynamic equilibrium with C4b binding protein
      (C4bBP), thus affecting the measurement of free protein S antigen. We addressed
      the issue of overestimation of the free protein S concentration with current
      immunoassays due to the dynamic equilibrium and propose a new method for its
      accurate determination. Our assay system was tested at different reaction
      temperatures using purified free protein S, protein S-C4bBP complexes, plasma
      samples, and a commercially available free protein S assay kit. At a reaction
      temperature of 37 degrees C, the free protein S fraction increased from 0.5 ng/ml
      (at 4 degrees C) to 7.8 ng/ml, and from 4.5 ng/ml (at 4 degrees C) to 56 ng/ml
      when the concentration of the assayed protein S-C4bBP complexes was 20 ng/ml and
      200 ng/ml, respectively. In plasma samples, free protein S levels were
      approximately 0.8 microg/ml and 6 pg/ml higher at 25 degrees C and 37 degrees C,
      respectively compared to measurements at 4 degrees C. Measurements of free
      protein S in plasma using a commercially available assay kit were approximately
      0.6 microg/ml higher at 25 degrees C than measurements performed at 4 degrees C.
      Dynamic equilibrium between protein S and C4bBP affects the measurement of free
      protein S antigen. Measurement of free protein S antigen should be performed
      under conditions where protein S is not dissociated from protein S-C4bBP
      complexes, as exemplified by assay at low temperature (4 degrees C).

PMID- 12211650
TI  - Immunoassay of anti-thyroid autoantibodies: high analytical variability in second
      generation methods.
AB  - The use of highly sensitive immunometric methods in clinical laboratories to
      assay anti-thyroid antibodies has progressively expanded in recent years but it
      is not known whether the new techniques have improved the analytical variability
      connected with the preceding methodologies. The Italian Society of Laboratory
      Medicine Study Group on Autoimmune Diseases conducted a collaborative study with
      the biomedical industry to evaluate the degree of standardization of the new
      analytical procedures. Twelve companies agreed to participate in the study on the
      search for anti-thyroglobulin (anti-Tg) and anti-thyroperoxidase (anti-TPO)
      antibodies in nine sera from patients with autoimmune thyroiditis, and in six
      sera from patients with non-autoimmune thyroid disease; ten immunometric and
      three immunofluorescence methods were employed. Agreement of qualitative results
      was close to 90% for anti-Tg and 97% for anti-TPO, with no important differences
      between the methods; variability of the quantitative results, expressed as CV% of
      absolute (in lU/ml) and relative (in cut-off concentration multiples) values was
      93.9% and 102.3%, respectively, for anti-Tg, and 75.5% and 62.9%, respectively,
      for anti-TPO. These findings show that despite the progressive improvement in the
      analytical techniques, the variability between methods for the assay of anti-Tg
      and anti-TPO is still unexpectedly high, and probably due to several factors such
      as uncertainty in defining the positive cutoff concentration, absence of adequate
      international reference preparations, modality of autoantigen purification, and
      analytical variability in the assay procedures.

PMID- 12211651
TI  - The measurement of insulin-like growth factor-I (IGF-I) concentration in random
      urine samples.
AB  - The aim of the present study was to assess a suitable expression of the urinary
      concentration of a protein/ peptide hormone such as insulin-like growth factor-I
      (IGF-I), measured in the urine of healthy individuals when the specimen
      collection is executed randomly. One hundred and twenty male subjects were
      divided by age into four groups, namely healthy sedentary young (SYA) and older
      (SOA) adults, older (OC) and young (YC) children. In a single urine specimen,
      randomly collected during the morning from each individual, total urinary IGF-I
      was measured by immunoradiometric method, and urinary creatinine (uCr) and total
      proteins (utPr) were measured by capillary electrophoresis and spectrophotometric
      methods, respectively. The urinary IGF-I concentrations were not significantly
      different in all groups investigated and they were (mean +/- SD): 82.7 +/- 82.8
      ng/l, 103.5 +/- 83.3 ng/l, 80.4 +/- 64.4 ng/l in OC, SYA and SOA, respectively;
      only in the YC group there was a tendency to higher values (125.2 +/- 93.2 ng/l)
      compared with the other groups. utPr ranged from 26 to 40 mg/l and did not
      demonstrate significant differences between groups. The urinary IGF-I correlated
      with uCr and utPr, and statistical significance was observed in all measurements.
      The measurement of urinary IGF-I in random urine and its ratio to utPr is an
      innovative, useful way of investigation of urinary protein/peptide hormones.

PMID- 12211652
TI  - Urinary bikunin determination provides insight into proteinase/proteinase
      inhibitor imbalance in patients with inflammatory diseases.
AB  - Bikunin (BK) is a Kunitz-type proteinase inhibitor responsible for most of the
      antitryptic activity of urine and so is known as the urinary trypsin inhibitor.
      As its excretion increases in inflammatory conditions, it is often considered to
      be a positive acute phase protein (APP). However, the gene for BK is
      downregulated in inflammation. In human plasma the major part of BK is covalently
      linked through a glycosaminoglycan chain to one or two homologous peptide heavy
      chains, thus forming high molecular weight proteinase inhibitors called pre-alpha
      inhibitor (PalphaI) and inter-alpha-inhibitor (IalphaI), respectively. The C
      terminal parts of these heavy chains are very sensitive to proteolysis.
      Neutrophil proteinases in particular are able to release from IalphaI and PalphaI
      BK (M, about 25,000) which retains its antitryptic activity and is quickly
      excreted in urine. It was therefore an early supposition that the higher urinary
      excretion of BK occurring during inflammatory diseases should be, at least in
      some respect, related to a partial proteolysis of IalphaI and PalphaI. In this
      study we observed that BK, determined as antitryptic activity, was clearly
      increased in urine from 35 patients with inflammatory diseases varying in origin
      and severity (76.5 +/- 75.5 IU/g vs. reference value <10 IU/g creatinine). This
      increase seems mainly to be associated with polymorphonuclear leukocyte
      activation, monitored by human leukocyte elastase (HLE) determination rather than
      with the acute phase response assessed by C-reactive protein (CRP) measurement.
      For all the patients we found that the urinary levels of BK and serum
      concentration of intact IalphaI correlated inversely (r=-0.36; p=0.03), in
      agreement with the presumed precursor-product relationship linking IalphaI and
      BK. We also proved that urinary BK was significantly higher, and serum IalphaI
      was significantly lower, in samples with plasma HLE values above the reference:
      90 microg/l. Taken together, our results demonstrate that BK, the urinary
      excretion of which is increased in inflammatory conditions, originates, at least
      partly, from IalphaI and PalphaI by proteolytic cleavage. Consequently, urinary
      BK determination provides information on the severity of systemic proteolysis
      occurring in inflammation. We also demonstrated that during inflammatory diseases
      IalphaI and PalphaI concentrations in serum are dependent on their increased
      utilization as well as on the regulation of their biosynthesis.

PMID- 12211654
TI  - Comparison of laser-probe and photometric determination of the urinary
      crystallization risk of calcium oxalate.
AB  - A variety of equipment is used for the observation of precipitation processes
      which occur in urinary samples. The Bonn-Risk-Index, a measure of the calcium
      oxalate crystallization risk of human urine, has been developed with the use of
      an in-line laser-probe gauge. For basic research or in clinical laboratories,
      however, this instrument, which fulfills industrial requirements for the
      evaluation of particle size distributions, is not widely available. The
      evaluation of an alternative method to determine the Bonn-Risk-Index based on a
      more commonly available apparatus would therefore be useful. In vitro
      crystallization experiments with 124 native urine samples from stone-forming and
      non-stone forming individuals were performed in order to determine their
      crystallization risk according to the Bonn-Risk-Index approach. The onset of an
      induced urinary crystallization was detected by simultaneous sample monitoring
      with an in-line laser-probe and a conventional dip-in photometer. A decrease of
      the sample's relative light transmissivity from initially 100% to 98% was assumed
      to be a reliable photometer-based criterion to indicate that crystallization
      actually began. The laser-probe signal was set as the reference measure. Linear
      regression analysis of the results of the laser-probe and the photometer-based
      Bonn-Risk-Index determinations reveals a significant and close correlation
      between the two measures. Method comparison by statistical evaluation shows i)
      that no significant deviation from linearity exists and ii) that both methods are
      statistically identical. The differences in the results are small enough to be
      confident that the photometer can be used in place of the laser-probe for
      clinical purposes. The photometer is a reliable, easy-to-use and cost-effective
      method for the determination of a triggered crystallization event in a urine
      sample. The assumed 98% criterion allows the determination of the Bonn-Risk-Index
      with adequate accuracy.

PMID- 12211653
TI  - Breath markers and soluble lipid peroxidation markers in critically ill patients.
AB  - Free radical-mediated inflammatory processes account for a great portion of
      morbidity and mortality in critically ill patients. The purpose of this study was
      to determine two plasma peroxidation markers and three volatile markers related
      to lipid peroxidation, metabolic activity and cholesterol metabolism, and to
      explore relationships between the different markers and patients' clinical
      status. Substances were analyzed in whole blood and in exhaled air in patients
      with head injury, acute respiratory distress syndrome (ARDS) and in those being
      at risk of developing ARDS. These results were compared with the baseline
      measurements in healthy individuals. Additionally, patients were assessed
      according to their inflammatory status. Concentrations of malondialdehyde and
      thiobarbituric acid-reactive substances in plasma as well as pentane
      concentrations in breath increased with increasing inflammatory status. Although
      these compounds are generated through peroxidation of fatty acids, concentrations
      of these markers were significantly different in patient groups. Isoprene
      concentrations were lowest in the ARDS group. Acetone concentrations were not
      different between patient groups. We conclude that for the assessment of lipid
      peroxidation and other inflammatory reactions a set of parameters has to be
      defined. More detailed insights into inflammatory processes can be obtained when
      the volatile markers and the serum markers are considered together.

PMID- 12211655
TI  - Comparison of first trimester, second trimester and integrated Down's syndrome
      screening results in unaffected pregnancies.
AB  - Our aim was to compare the results of first trimester combined test, second
      trimester triple test, and integrated test in the same pregnant population. We
      retrospectively studied 927 women, all giving birth to an unaffected baby except
      for two cases of Down's syndrome. The women underwent a nuchal translucency
      ultrasound measurement and a blood sampling for pregnancy-associated plasma
      protein A and free beta-hCG subunit (free total chorionic gonadotropin subunit)
      assay in the first trimester of pregnancy. A second trimester biochemical
      screening (alpha-fetoprotein, unconjugated oestriol and total hCG) was performed
      later. The correlations between each pair of markers and between each marker
      level and maternal age were calculated. No marker showed significant correlation
      with any other or with maternal age, with the obvious exception of free beta-hCG
      subunit and total hCG. The false-positive rate (cut-off level: 1 in 350 at term)
      was 1.5% for the first trimester test, 3.6% for the second trimester test and
      0.54% for the integrated test. In 10/14 pregnancies, the increased risk in the
      first trimester was not confirmed neither in the second trimester nor by the
      integrated test. In 29/33 women with an increased risk in the second trimester,
      the first trimester and the integrated test results were discordant. The absence
      of correlation among different marker levels suggests that the information
      supplied by the first and second trimester tests is different. Integrating first
      and second trimester markers in a single test could pose the ethical problem of
      withholding first trimester results and thus denying the possible advantages of
      an earlier pregnancy termination.

PMID- 12211656
TI  - Anti-phospholipid antibodies in diabetes mellitus.
AB  - The presence of autoantibodies to phospholipids may be associated with various
      pathological disorders; diabetes could be one of them because of the changes
      occurring in lipid metabolism but there are only few reports examining this
      question, and they are not always leading to the same conclusions because of the
      differences in the procedures or in the phospholipids tested. We carried out a
      systematic comparative study of diabetic serum antibody binding to all
      phospholipids, anionic and zwitterionic, by a quantitative ELISA. The implication
      of the hydrophobic moiety of the lipids was also studied: the presence of
      autoantibodies to the fatty acyl chains was investigated. Our results show the
      presence of anti-phospholipid antibodies in diabetic sera, particularly anti
      phosphatidylinositol and anti-phosphatidylcholine which have never been tested
      before, and appear to be associated with macroangiopathic complications. The
      antigenic epitopes are mainly the polar heads as no antibody binding to the
      hydrophobic moiety was observed. We discuss the relation of those antibodies to
      the angiopathic complications and to the direct effects of hyperglycemia on lipid
      antigenicity.

PMID- 12211658
TI  - The changes of superoxide dismutase, catalase and glutathione peroxidase
      activities in erythrocytes of active and passive smokers.
AB  - Cigarette smoking has been implicated in the pathogenesis of ischemic heart
      disease, emphysema, obstructive lung disease and neoplastic disorders. More than
      1000 constituents of smoke, including many oxidants, pro-oxidants, free radicals
      and reducing agents, have been identified. The activities of erythrocyte
      superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px),
      which are the important components of antioxidant defense system, were measured
      in 100 healthy volunteers. This study included heavy smokers (consuming
      cigarettes > or = 20 per day; n=30, group I), light smokers (consuming
      cigarettes<20 per day; n=30, group II), passive smokers (exposed to cigarette
      smoke in the indoor environment; n=20, group III), and non-smokers (n=20, the
      control group). While activities of SOD and CAT in erythro cytes were
      significantly lower in groups I, II and III than in the control group (p<0.01 for
      all), mean erythrocyte GSH-Px activity in group III was higher than that in
      groups l, II and in controls. These results suggest that the increased oxidative
      stress occurs in smokers, owing to the free radicals present in smoke. It might
      cause a decrease in antioxidant enzyme activities and oxidant/antioxidant
      imbalance. We also observed that passive smokers were affected by the
      environmental smoke to the same extent as active smokers.

PMID- 12211657
TI  - Alteration of serum enzymes in primary hypothyroidism.
AB  - In order to study the relationships between serum enzymes and the degree of
      hypothyroidism, 114 patients with primary hypothyroidism aged from 7 to 65 years
      were investigated. Forty one percent of patients exhibited normal levels of serum
      enzymes, while 59% had high levels either alone or in combination. The frequency
      of enzyme elevation was as follows: creatine kinase: 37%, aspartate
      aminotransferase: 35%, alanine aminotransferase: 29%, amylase: 15%, alkaline
      phosphatase: 3%. No significant correlation between thyroid stimulating hormone
      and serum enzyme levels was observed. This was due to highly variable release of
      enzymes from cells resulting presumably from individual metabolic set-point.
      Replacement therapy with thyroxine resulted in remarkable lowering of creatine
      kinase not only from high level to normal as early as 3 weeks even before
      normalization of thyroid stimulating hormone, but also from high normal to low
      normal level. The elevation of amylase and its response to thyroxine is being
      reported for the first time.

PMID- 12211659
TI  - Internal quality control system for non-stationary, non-ergodic analytical
      processes based upon exponentially weighted estimation of process means and
      process standard deviation.
AB  - The analytical processes in clinical laboratories should be considered to be non
      stationary, non-ergodic and probably non-stochastic processes. Both the process
      mean and the process standard deviation vary. The variation can be different at
      different levels of concentration. This behavior is shown in five examples of
      different analytical systems: alkaline phosphatase on the Hitachi 911 analyzer
      (Roche), vitamin B12 on the Access analyzer (Beckman), prothrombin time and
      activated partial thromboplastin time on the STA Compact analyzer (Roche) and PO2
      on the ABL 520 analyzer (Radiometer). A model is proposed to assess the status of
      a process. An exponentially weighted moving average and standard deviation was
      used to estimate process mean and standard deviation. Process means were
      estimated overall and for each control level. The process standard deviation was
      estimated in terms of within-run standard deviation. Limits were defined in
      accordance with state of the art- or biological variance-derived cut-offs. The
      examples given are real, not simulated, data. Individual control sample results
      were normalized to a target value and target standard deviation. The normalized
      values were used in the exponentially weighted algorithm. The weighting factor
      was based on a process time constant, which was estimated from the period between
      two calibration or maintenance procedures. The proposed system was compared with
      Westgard rules. The Westgard rules perform well, despite the underlying
      presumption of ergodicity. This is mainly caused by the introduction of the
      starting rule of 12s, which proves essential to prevent a large number of rule
      violations. The probability of reporting a test result with an analytical error
      that exceeds the total allowable error was calculated for the proposed system as
      well as for the Westgard rules. The proposed method performed better. The
      proposed algorithm was implemented in a computer program running on computers to
      which the analyzers were linked on-line. Each result was evaluated on-line, and a
      limit violation was immediately reported. The system has performed satisfactorily
      in our laboratory for ten analyzers for over 1 year.

PMID- 12211660
TI  - Evaluation of commutability of control materials.
AB  - The commutability of 13 control materials was evaluated by performing parallel
      measurements on two different analysers: a Synchron CX-5 Delta from Beckman
      Coulter and a Vitros 950 from Ortho-Clinical Diagnostics. Twenty three clinical
      chemistry analytes (substrates, electrolytes and enzymatic activities) were
      determined in plasma from 15 different patients in order to define intermethod
      relationship for each analyte. The relationship observed for each control
      material was compared to those obtained for patients' specimens. The results show
      that commutability depends both on the tested analyte and on the control
      material. No totally commutable material has been found for the whole set of
      tested parameters. Most control materials were commutable for inorganic
      phosphate, glucose, chloride, triglycerides, alanine aminotransferase, amylase
      and y-glutamyltransfera-se, but less than a quarter of control materials were
      commutable for sodium, calcium, creatinine, alkaline phosphatase and lipase.
      Seven materials were commutable for more than half of the analytes, whereas five
      control materials were commutable for less than a quarter of these analytes. We
      propose to verify the commutability of materials before their use in an external
      quality control assessement.

PMID- 12211661
TI  - IFCC primary reference procedures for the measurement of catalytic activity
      concentrations of enzymes at 37 degrees C. Part 1. The concept of reference
      procedures for the measurement of catalytic activity concentrations of enzymes.
AB  - This paper is the first in a series dealing with reference procedures for the
      measurement of catalytic activity concentrations of enzymes at 37 degrees C and
      with the certification of reference preparations. Other parts deal with: Part 2.
      Reference Procedure for the Measurement of Catalytic Concentration of Creatine
      Kinase; Part 3. Reference Procedure for the Measurement of Catalytic
      Concentration of Lactate Dehydrogenase; Part 4. Reference Procedure for the
      Measurement of Catalytic Concentration of Alanine Aminotransferase; Part 5.
      Reference Procedure for the Measurement of Catalytic Concentration of Aspartate
      Aminotransferase; Part 6. Reference Procedure for the Measurement of Catalytic
      fication of Four Reference Materials for the Determination of Enzymatic Activity
      of y-Glutamyltransferase, Lactate Dehydrogenase, Alanine Aminotransferase and
      Creatine Kinase at 37 degrees C. A document describing the determination of
      preliminary reference values is also in preparation.

PMID- 12211662
TI  - IFCC primary reference procedures for the measurement of catalytic activity
      concentrations of enzymes at 37 degrees C. Part 2. Reference procedure for the
      measurement of catalytic concentration of creatine kinase.
AB  - This paper is the second in a series dealing with reference procedures for the
      measurement of catalytic activity concentrations of enzymes at 37 degrees C and
      the certification of reference preparations. Other parts deal with: Part 1. The
      Concept of Reference Procedures for the Measurement of Catalytic Activity
      Concentrations of Enzymes; Part 3. Reference Procedure for the Measurement of
      Catalytic Concentration of Lactate Dehydrogenase; Part 4. Reference Procedure for
      the Measurement of Catalytic Concentration of Alanine Aminotransferase; Part 5.
      Reference Procedure for the Measurement of Catalytic Concentration of Aspartate
      Aminotransferase; Part 6. Reference Procedure for the Measurement of Catalytic
      Concentration of gamma-Glutamyltransferase; Part 7. Certification of Four
      Reference Materials for the Determination of Enzymatic Activity of gamma
      Glutamyltransferase, Lactate Dehydrogenase, Alanine Aminotransferase and Creatine
      Kinase at 37 degrees C. A document describing the determination of preliminary
      reference values is also in preparation. The pro- described 30 degrees C IFCC
      reference method (1). Differences are tabulated and commented on in Appendix 3.

PMID- 12211663
TI  - IFCC primary reference procedures for the measurement of catalytic activity
      concentrations of enzymes at 37 degrees C. Part 3. Reference procedure for the
      measurement of catalytic concentration of lactate dehydrogenase.
AB  - This paper is the third in a series dealing with reference procedures for the
      measurement of catalytic activity concentrations of enzymes at 37 degrees C and
      the certification of reference preparations. Other parts deal with: Part 1. The
      Concept of Reference Procedures for the Measurement of Catalytic Activity
      Concentrations of Enzymes; Part 2. Reference Procedure for the Measurement of
      Catalytic Concentration of Creatine Kinase; Part 4. Reference Procedure for the
      Measurement of Catalytic Concentration of Alanine Aminotransferase; Part 5.
      Reference Procedure for the Measurement of Catalytic Concentration of Aspartate
      Aminotransferase; Part 6. Reference Procedure for the Measurement of Catalytic
      Concentration of gamma-Glutamyltransferase; Part 7. Certification of Four
      Reference Materials tamyltransferase, Lactate Dehydrogenase, Alanine
      Aminotransferase and Creatine Kinase at 37 degrees C. A document describing the
      determination of preliminary upper reference limits is also in preparation. The
      procedure described here is deduced from the previously described 30 degrees C
      IFCC reference method (1). Differences are tabulated and commented on in Appendix
      1.

PMID- 12211664
TI  - The Ionising Radiation (Medical Exposure) regulations (IRME) 2000--radiological
      considerations.
AB  - 1) IRME regulations apply to the trust and not to the individual clinician. 2)
      Each trust must have written regulations outlining how the IRME regulations are
      to be applied locally. 3) The IRME regulations and, almost certainly, the local
      directions, have the force of the law and breaches may be dealt with by both the
      criminal and the civil courts. 4) All radiological examinations using ionising
      radiation must be reported either by a radiologist or a clinician, and the report
      must be filed in the patient's case notes. 5) It is unlawful to request a
      radiological examination if it is not to be reported. 6) No regulation mentions
      the quality or timeliness of the radiological report.

PMID- 12211665
TI  - Fusion of the lumbar spine. A consideration of the indications.

PMID- 12211666
TI  - The history of fractures of the proximal femur. The contribution of the Dublin
      Surgical School in the first half of the 19th century.
AB  - The designation 'Adam Bogen' (arch) which is used in the German literature as a
      description of the thick medial cortex of the femoral neck is incorrect. This
      arch was described by Robert Adams (1795-1871), who was an Irish anatomist and
      surgeon. Adams, Colles and Smith were outstanding surgeons who described
      fractures of the proximal femur in detail during the first half of the 19th
      century and who together formed the Dublin Surgical School. The most important
      aspects of these fractures were described between 1818 and 1839.

PMID- 12211667
TI  - Injury to the lateral femoral cutaneous nerve during harvest of iliac bone graft,
      with reference to the size of the graft.
AB  - In patients who underwent autogenous iliac bone grafting we studied prospectively
      injury to the lateral femoral cutaneous nerve (LFCN) in relation to the size
      (length, depth, width) of the graft. We also examined the neurological deficit,
      by questioning them about numbness and/or pain in the lateral thigh. The risk of
      injury was significantly higher in those in whom the depth of the graft was more
      than 30 mm. With regard to the length of the graft the incidence of nerve injury
      was 20% when the graft was 45 mm long or more, 16% when it was between 30 mm and
      45 mm long, and 8% when it was less than 30 mm long. We should inform patients of
      the possibility of such injury, and take size into consideration when harvesting
      grafts from the ilium.

PMID- 12211668
TI  - Wound healing after implant surgery in HIV-positive patients.
AB  - We performed a prospective, blind, controlled study on wound infection after
      implant surgery involving 41 procedures in patients infected with the human
      immunodeficiency virus (HIV) and 141 in HIV-negative patients. The patients were
      staged clinically and the CD4 cell count determined. Wound infection was assessed
      using the asepsis wound score. A risk category was allocated to account for
      presurgical contamination. In HIV-positive patients, with no preoperative
      contamination, the incidence of wound infection (3.5%) was comparable with that
      of the HIV-negative group (5%; p = 0.396). The CD4 cell count did not affect the
      incidence of infection (r = 0.16). When there was preoperative contamination, the
      incidence of infection in HIV-positive patients increased markedly (42%) compared
      with that in HIV-negative patients (11%; p = 0.084). Our results show that when
      no contamination has occurred implant surgery may be undertaken safely in HIV
      positive patients.

PMID- 12211669
TI  - Management of chronic pain in whiplash injury.
AB  - We investigated the response of chronic neck and shoulder pain to decompression
      of the carpal tunnel in 38 patients with whiplash injury. We also determined the
      plasma levels of substance P (SP) and calcitonin gene-related peptide (CGRP),
      which are inflammatory peptides that sensitise nociceptors. Compared with normal
      control subjects, the mean concentrations of SP (220 v 28 ng/l; p < 0.0001) and
      CGRP (400 v 85 ng/l; p < 0.0005) were high in patients with chronic shoulder and
      neck pain before surgery. After operation their levels fell to normal. There was
      resolution of neurological symptoms with improvement of pain in 90% of patients.
      Only two of the 30 with chronic neck and shoulder pain who had been treated
      conservatively showed improvement when followed up at two years. In spite of
      having neuropathic pain arising from the median nerve, all these patients had
      normal electromyographic and nerve-conduction studies. Chronic pain in whiplash
      injury may be caused by 'atypical' carpal tunnel syndrome and responds favourably
      to surgery which is indicated in patients with neck, shoulder and arm pain but
      not in those with mild symptoms in the hand. Previously, the presence of
      persistent neurological symptoms has been accepted as a sign of a poor outcome
      after a whiplash injury, but our study suggests that it may be possible to treat
      chronic pain by carpal tunnel decompression.

PMID- 12211670
TI  - Complex fractures of the distal humerus in the elderly. The role of total elbow
      replacement as primary treatment.
AB  - Between 1995 and 2000, 19 consecutive patients with fractures of the distal
      humerus were treated by primary total elbow replacement using the Coonrad-Morrey
      prosthesis. No patient had inflammatory or degenerative arthritis of the elbow.
      The mean age at the time of injury was 73 years (61 to 95). According to the AO
      classification, 11 patients had suffered a C3 injury, two a B3 and two an A3. One
      fracture was unclassified. Two patients died from unrelated causes and one was
      unable to be assessed because of concurrent illness. The mean time to follow-up
      was three years (1 to 5.5). At follow-up 11 patients (68%) reported no pain, four
      (25%) had mild pain with activity and one had mild pain at rest. The mean flexion
      arc was 24 degrees to 125 degrees. The mean supination was 90 degrees (70 to 100)
      and pronation 70 degrees (50 to 110). No elbow was unstable. The mean
      Disabilities of the Arm, Shoulder and Hand score was 23 (0.92 to 63.3) and the
      mean Mayo elbow performance score was 93 (80 to 100). Of the 16 patients, 15 were
      satisfied with the outcome. Radiological evaluation revealed only one patient
      with a radiolucent line at the cement-bone interface. It was between 1 and 2 mm
      in length, was present on the initial postoperative radiograph and was non
      progressive at the time of follow-up. Primary total elbow arthroplasty is an
      acceptable option for the management of comminuted fractures of the distal
      humerus in elderly patients when the configuration of the fracture and the
      quality of the bone make reconstruction difficult.

PMID- 12211671
TI  - Intertrochanteric osteotomy for avascular necrosis of the head of the femur.
      Survival probability of two different methods.
AB  - We have compared different types of intertrochanteric osteotomy for avascular
      necrosis of the hip and evaluated their performance in the light of improving
      outcome after total hip arthroplasty (THA). During a period of 14 years we
      performed 63 flexion osteotomies (partly combined with varus or valgus
      displacement), 29 rotational osteotomies, 13 varus osteotomies, eight medialising
      osteotomies and two extension osteotomies. The mean period of follow-up for all
      115 operations was 7.3 years (maximum 24.6). At follow-up, 27 of 29 patients with
      a rotational osteotomy had already undergone a THA, compared with 36 of 63 after
      flexion osteotomy. A high incidence of complications (55.2%) was seen early after
      rotational osteotomy, compared with 17.5% after flexion osteotomy. For all
      osteotomies there was a high correlation between the size of the necrotic area
      and the incidence of failure, which also correlated with the preoperative Ficat
      and Steinberg stages. Using Kaplan-Meier survivorship analysis, Sugioka's
      rotational osteotomy showed a survival probability after five years of 0.26 (95%
      confidence interval 0.49 to 0.14), and after ten years of 0.15 (CI 0.36 to 0.06).
      The survival probability for flexion osteotomy was 0.70 (CI 0.83 to 0.59) after
      five years and 0.50 (CI 0.65 to 0.38) after ten years. The subgroup of flexion
      osteotomy with a necrotic sector of less than 180 degrees achieved the best
      survival probability of 0.90 (CI 1.00 to 0.80) after five years and 0.61 (CI 0.84
      to 0.45) after ten years. The indications for intertrochanteric osteotomy for
      avascular necrosis of the hip have to be addressed critically. Even flexion
      osteotomy in cases with small areas of necrosis provides only temporary benefit.
      Rotational osteotomy was associated with a high incidence of complications.

PMID- 12211672
TI  - Migration of the femoral stem after impaction bone grafting. First results of an
      ongoing, randomised study of the exeter and elite plus femoral stems using
      radiostereometric analysis.
AB  - We report the initial results of an ongoing randomised, prospective study on
      migration of the Exeter and Elite Plus femoral stems after impaction
      allografting, as measured by radiostereometry. Clinically, the impaction
      technique gave good results for both stems. The mean subsidence in the first year
      was 1.30 mm and 0.20 mm for the Exeter and the Elite Plus stems, respectively. In
      the second year, the Exeter stem continued to subside further by a mean of 0.42
      mm, while the Elite Plus stem did not do so. Subsidence of the Exeter stem
      correlated with deficiency of bone stock as graded on the Gustilo and Pasternak
      scale. This correlation was not found for the Elite Plus stem. None of the other
      parameters which were studied predisposed to subsidence. There was no significant
      association between the amount of subsidence and the radiological appearance of
      the graft for either stem. Our findings do not support the theory that radial
      compression, due to subsidence of the Exeter stem, is the essential stimulus for
      remodelling in impaction allografting.

PMID- 12211673
TI  - The type of cement and failure of total hip replacements.
AB  - Using data from the Norwegian Arthroplasty egister, we have assessed the survival
      of 17 323 primary Charnley hip prostheses in patients with osteoarthritis based
      upon the type of cement used for the fixation of the implant. Overall, 9.2% had
      been revised after follow-up for ten years; 71% of the failures involved aseptic
      loosening of the femoral component. We observed significantly increased rates of
      failure for prostheses inserted with CMW1 and CMW3 cements. Using implants fixed
      with gentamicin-containing Palacos cement as the reference, the adjusted Cox
      regression failure rate ratios were 1.1 (95% CI 0.9 to 1.4) for implants cemented
      with plain Palacos, 1.1 (95% CI 0.7 to 1.6) for Simplex, 2.1 (95% 1.5 to 2.9) for
      gentamicin-containing CMW1, 2.0 (95% CI 1.6 to 2.4) for plain CMW1 and 3.0 (95%
      CI 2.3 to 3.9) for implants fixed with CMW3 cement. The adjusted failure rate at
      ten years varied from 5.9% for implants fixed with gentamicin-containing Palacos
      to 17% for those fixed with CMW3.

PMID- 12211674
TI  - The performance of two hydroxyapatite-coated acetabular cups compared with
      Charnley cups. From the Norwegian Arthroplasty Register.
AB  - We have compared the survival of two hydroxyapatite (HA)-coated cups, 1208 Atoll
      hemispheric and 2641 Tropic threaded, with cemented Charnley all-polyethylene
      cups (16 021) using the Cox regression model. The Tropic cup used in combination
      with an alumina ceramic femoral head, had good results, similar to those of the
      Charnley cup. When used in combination with a stainless-steel head, however, the
      risk of revision beyond four years was increased 3.4 times for the Tropic cup
      compared with the Charnley cup (p < 0.001). Over the same period, the Atoll cup
      had an increased risk of revision of 3.8 times when used with the alumina heads
      (p < 0.001) and an increased risk of 6.1 times when used with stainless-steel
      heads (p < 0.001). Revision because of wear and osteolysis was more common with
      both types of HA-coated cup than with the Charnley cup. The rate of revision of
      the Atoll cup because of aseptic loosening was also increased. We found that HA
      coated cups did not perform better than the Charnley cup.

PMID- 12211675
TI  - Meniscofemoral ligaments revisited. Anatomical study, age correlation and
      clinical implications.
AB  - The meniscofemoral ligaments were studied in 84 fresh-frozen knees from 49
      cadavers. Combined anterior and posterior approaches were used to identify the
      ligaments. In total, 78 specimens (93%) contained at least one meniscofemoral
      ligament. The anterior meniscofemoral ligament (aMFL) was present in 62 specimens
      (74%), and the posterior meniscofemoral ligament (pMFL) in 58 (69%). The 42
      specimens (50%) in which both ligaments were present were from a significantly
      younger population than that with one MFL or none (p < 0.05). Several anatomical
      variations were identified, including oblique fibres of the posterior cruciate
      ligament (PCL), which were seen in 16 specimens (19%). These were termed the
      'false pMFL'. The high incidence of MFLs and their anatomical variations should
      be borne in mind during arthroscopic and radiological examination of the PCL. It
      is important to recognise the oblique fibres of the PCL on MRI in order to avoid
      wrongly identifying them as either a pMFL or a tear of the lateral meniscus. The
      increased incidence of MFLs in younger donors suggests that they degenerate with
      age.

PMID- 12211676
TI  - The Johnson-Elloy (Accord) total knee replacement. Poor results at 8 to 12 years.
AB  - We have found poor mid-term results in a multisurgeon series of 94 Johnson-Elloy
      (Accord) total knee replacements. A total of 27 knees (29%) has required
      revision, in 26 for aseptic loosening. Only 18 (19%) remain in situ, and these
      give poor function, are painful and most show radiological evidence of early
      failure. At 12 to 13 years the survival rate is 43% (confidence interval 29 to
      57) with failure requiring revision as the endpoint. Proximal migration of the
      femoral component is associated with considerable loss of bone stock. We believe
      that all patients who have this implant should be recalled for regular review in
      order to anticipate this problem.

PMID- 12211677
TI  - Tourniquet-induced restriction of the quadriceps muscle mechanism. Fact or
      fiction?
AB  - Many knee surgeons flex the knee and sometimes also extend the hip before
      inflating a tourniquet on the thigh. This practice stems from the belief that
      these manoeuvres prevent excessive strain on the quadriceps during surgery, the
      assumption being that movement of the muscle is restricted by an inflated
      tourniquet. We therefore examined, using ultrasound, the movement of the
      quadriceps muscle above and below the tourniquet before and after inflation. We
      applied a tourniquet of standard size to the thigh of five volunteers for
      approximately five minutes. A bubble of air was injected into the quadriceps
      muscle above the tourniquet and was the proximal point of reference. The
      musculotendinous junction was the distal point. The movement of the reference
      point was measured by ultrasound before and after inflation of the tourniquet.
      Each measurement was repeated with either the knee flexed and the hip extended,
      or the hip flexed and the knee extended. The mean and standard deviation were
      recorded. Before inflation the mean amount of passive movement was 1.1 +/- 0.13
      cm proximal and 4.0 +/- 0.08 cm distal to the tourniquet, with a range of
      movement of the knee of 0 degrees to 137 degrees (6.7 degrees). After inflation
      the mean passive movement was 1.0 +/- 0.07 cm proximal and 4.0 +/- 0.08 cm distal
      to the tourniquet with a range of 0 degrees to 132 degrees (+/- 7.6 degrees). The
      ultrasound findings therefore have shown no evidence of restriction of the
      quadriceps muscle by an inflated tourniquet.

PMID- 12211678
TI  - Extramedullary or intramedullary tibial alignment guides: a randomised,
      prospective trial of radiological alignment.
AB  - We undertook a prospective, randomised study of 135 total knee arthroplasties to
      determine the most accurate and reliable technique for alignment of the tibial
      prosthesis. Tibial resection was guided by either intramedullary or
      extramedullary alignment jigs. Of the 135 knees, standardised postoperative
      radiographs suitable for assessment were available in 100. Correct tibial
      alignment was found in 85% of the intramedullary group compared with 65% of the
      extramedullary group (p = 0.019). We conclude that intramedullary guides are
      superior to extramedullary instruments for alignment of the tibial prosthesis.

PMID- 12211679
TI  - Deterioration of long-term clinical results after the Elmslie-Trillat procedure
      for dislocation of the patella.
AB  - We examined 39 patients (45 knees) who had undergone an Elmslie-Trillat procedure
      for recurrent or habitual dislocation of the patella with a follow-up of more
      than ten years. The mean age at the time of surgery was 18.4 years; the mean
      follow-up was 161 months (120 to 238). Using Fulkerson's functional knee score,
      41 knees (91%) had an excellent or good result at a mean follow-up of 45 months,
      and this was maintained in 29 (64%) at the final review. The main cause of
      deterioration in the clinical results was the onset or worsening of
      patellofemoral joint pain, not patellar instability.

PMID- 12211680
TI  - Rotationplasty after failure of a knee prosthesis for a malignant tumour of the
      distal femur.
AB  - Failure of massive knee endoprostheses implanted for malignant tumours of the
      distal femur in children presents a difficult problem. We present the results of
      rotationplasty undertaken under these circumstances in four boys. They had been
      treated initially at a mean age of 9.5 years for a stage-IIB malignant tumour of
      the distal femur by resection and implantation of a massive knee endoprosthesis.
      After a mean period of eight years and a mean of four operative procedures, there
      was failure of the endoprosthesis because of aseptic loosening in two and
      infection in two. Function was poor with a mean Musculoskeletal Tumor Society
      score of 7.5/30, and considerable associated psychological problems. At a mean
      follow-up of 4.5 years after rotationplasty there was excellent function with a
      mean score of 27.5/30 and resolution of the psychological problems.

PMID- 12211681
TI  - Eosinophilic granuloma. A different behaviour in children than in adults.
AB  - Localised Langerhans-cell histiocytosis of bone (eosinophilic granuloma) is a
      benign tumour-like condition with a variable clinical course. Different forms of
      treatment have been reported to give satisfactory results. However, previous
      series all contain patients with a wide age range. Our aim was to investigate the
      effect of skeletal maturity on the rate of recurrence of isolated eosinophilic
      granuloma of bone excluding those arising in the spine. We followed up 32
      patients with an isolated eosinophilic granuloma for a mean of five years; 17
      were skeletally immature. No recurrences were noted in the skeletally immature
      group even after biopsy alone. By contrast, four of 13 skeletally mature patients
      had a recurrence and required further surgery. This suggests that eosinophilic
      granuloma has a low rate of recurrence in skeletally immature patients.

PMID- 12211682
TI  - The treatment of sacral giant-cell tumours by serial arterial embolisation.
AB  - Giant-cell tumours of the sacrum are difficult to treat. Surgery carries a high
      risk of morbidity, local recurrence and mortality. Radiation is effective in some
      patients, but has a risk of malignant change. We evaluated the effectiveness of
      serial arterial embolisation as an alternative to surgery. Five patients with
      giant-cell tumours of the sacrum which had been primarily treated by serial
      embolisation were retrospectively reviewed for changes in the size of the tumour.
      In four the symptoms resolved with full return of function and arrest in the
      growth of the tumour. They remained free from growth, recurrence, or metastases
      at follow-up (4 to 17 years). One patient died from metastatic disease within 18
      months of the initial diagnosis.

PMID- 12211683
TI  - Screening of neonatal instability and of developmental dislocation of the hip. A
      survey of 132,601 living newborn infants between 1956 and 1999.
AB  - Between 1956 and 1999, 132,601 living children were born in Malmo, and screened
      for neonatal instability of the hip. All late diagnosed patients have been
      followed and re-examined clinically and radiologically. During the first years of
      screening, less than five per 1,000 living newborn infants were treated. This
      figure increased to 35 per 1000 in 1980, but later diminished again to about six
      per 1,000 annually after 1990. The number of referred cases decreased from 45 per
      1,000 in 1980 to between 10 to 15 per 1,000 from 1990. During the period of high
      rates of referral and treatment a larger number of paediatricians were involved
      in the screening procedure than during the periods with low rates of ferral and
      treatment. Altogether 21 patients (0.16 per 1,000) with developmental dislocation
      of the hip were diagnosed late, after one week. At follow-up, 18 were free from
      symptoms and 15 considered to be diologically normal.

PMID- 12211684
TI  - Universal or selective screening of the neonatal hip using ultrasound? A
      prospective, randomised trial of 15,529 newborn infants.
AB  - The aim of this study was to evaluate whether universal (all neonates) or
      selective (neonates belonging to the risk groups) ultrasound screening of the
      hips should be recommended at birth. We carried out a prospective, randomised
      trial between 1988 and 1992, including all newborn infants at our hospital. A
      total of 15 529 infants was randomised to either clinical screening and
      ultrasound examination of all hips or clinical screening of all hips and
      ultrasound examination only of those at risk. The effect of the screening was
      assessed by the rate of late detection of congenital or developmental hip
      dysplasia in the two groups. During follow-up of between six and 11 years, only
      one late-detected hip dysplasia was seen in the universal group, compared with
      five in the subjective group, representing a rate of 0.13 and 0.65 per 1,000,
      respectively. The difference in late detection between the two groups was not
      statistically significant (p = 0.22). When clinical screening is of high quality,
      as in our study, the effect of an additional ultrasound examination, measured as
      late-presenting hip dysplasia, is marginal. Under such circumstances, we consider
      that universal ultrasound screening is not necessary, but recommend selective
      ultrasound screening for neonates with abnormal or suspicious clinical findings
      and those with risk factors for hip dysplasia.

PMID- 12211685
TI  - Congenital abnormalities of the urogenital tract in association with congenital
      vertebral malformations.
AB  - There is a close link between the embryological development of the
      musculoskeletal system and all other main organ systems. We report a prospective
      series of 202 patients with congenital vertebral abnormalities and document the
      associated abnormalities in other systems. There were 100 boys and 102 girls. In
      153 there were 460 associated abnormalities, a mean of 2.27 abnormalities for
      each patient. Intravenous pyelography was carried out on 173 patients (85.6%) and
      ultrasonography on the remaining 29 (14.4%). Patients with genitourinary
      anomalies were more likely to have musculoskeletal (p = 0.002), gastrointestinal
      (p = 0.02) and cardiac abnormalities (p = 0.008) than those without genitourinary
      involvement. A total of 54 (26.7%) had at least one genitourinary abnormality,
      the most frequent being unilateral renal agenesis. There was urinary obstruction
      in six (3%). There was no association between genitourinary abnormality and the
      place of birth, parental age, birth order, level of spinal curvature, or the
      number, type and side of spinal anomaly. There was, however, a statistically
      significant association (p = 0.04) between costal and genitourinary
      abnormalities. The incidence of genitourinary abnormalities (26.7%) was similar
      to that of previously reported series. The diagnosis of a congenital vertebral
      abnormality should alert the clinician to a wide spectrum of possible associated
      anomalies most of which are of clinical importance.

PMID- 12211686
TI  - Humeral osteonecrosis leading to the early detection of a bronchial carcinoma.
AB  - The new Ionising Radiation (Medical Exposure) Regulations 2000 (IR (ME)ER) were
      implemented in January 2001. These regulations state that "the referrer must
      record in the patient's notes that a radiograph was taken and what it showed". As
      a result it is now incumbent upon the orthopaedic surgeon to document formally
      the findings of all requested radiographs. We present a case in which a left
      upper bronchial carcinoma was detected initially on a radiograph of the left
      shoulder. It highlights the importance of careful examination of the entire
      radiographic image and the documenting of the findings.

PMID- 12211687
TI  - An unusual case of a postoperative bone cyst.
AB  - We describe an unusual case of a postoperative bone cyst resulting from a
      retained fragment of surgical glove. We highlight some of the problems associated
      with gloves and suggest ways of safeguarding against similar complications.

PMID- 12211688
TI  - Mutual associations among microstructural, physical and mechanical properties of
      human cancellous bone.
AB  - Previous studies have shown that low-density, rod-like trabecular structures
      develop in regions of low stress, whereas high-density, plate-like trabecular
      structures are found in regions of high stress. This phenomenon suggests that
      there may be a close relationship between the type of trabecular structure and
      mechanical properties. In this study, 160 cancellous bone specimens were produced
      from 40 normal human tibiae aged from 16 to 85 years at post-mortem. The
      specimens underwent micro-CT and the microstructural properties were calculated
      using unbiased three-dimensional methods. The specimens were tested to determine
      the mechanical properties and the physical/compositional properties were
      evaluated. The type of structure together with anisotropy correlated well with
      Young's modulus of human tibial cancellous bone. The plate-like structure
      reflected high mechanical stress and the rod-like structure low mechanical
      stress. There was a strong correlation between the type of trabecular structure
      and the bone-volume fraction. The most effective microstructural properties for
      predicting the mechanical properties of cancellous bone seem to differ with age.

PMID- 12211689
TI  - Roentgen single-plane photogrammetric analysis (RSPA.) A new approach to the
      study of musculoskeletal movement.
AB  - We present a new approach for the accurate reconstruction of three-dimensional
      skeletal positions using roentgen single-plane photogrammetric analysis (RSPA).
      This technique uses a minimum of three markers embedded in each segment which
      allow continuous, real-time, internal skeletal movement to be measured from
      single-plane images, provided that the precise distance between the markers is
      known. A simulation study indicated that the error propagation in this approach
      is influenced by focus position, object position, the number of control points,
      the accuracy of the previous measurement of the distance between markers and the
      accuracy of image measurement. For reconstruction of normal movement of the knee
      with an input measurement error of SD = 0.02 mm, the rotational and translational
      differences between reconstructed and original movement were less than 0.27
      degrees and 0.9 mm, respectively. Our results showed that the accuracy of RSPA is
      sufficient for the analysis of most movement of joints. This approach can be
      applied in combination with force measurements for dynamic studies of the
      musculoskeletal system.

PMID- 12211690
TI  - Bone ingrowth in the presence of particulate polyethylene. Synergy between
      interface motion and particulate polyethylene in periprosthetic tissue response.
AB  - We have investigated whether the presence of polyethylene (PE) alone is
      sufficient to cause an aggressive periprosthetic tissue response, or whether
      certain mechanical interface conditions can allow bone to grow while in the
      presence of PE. An experimental implant was loaded in the presence and absence of
      particulate PE under stable and unstable conditions. Bone with a thin,
      discontinuous fibrous membrane formed in both groups of stable implants, either
      in the presence or absence of PE. By contrast, a continuous fibrous membrane
      consistently formed in both groups of unstable implants. The membrane consisted
      of loose fibrous connective tissue when PE was absent, and dense connective
      tissue with macrophages and a synovial lining when PE was present. In this model,
      if the interface was stable, the presence of PE was not sufficient to prevent the
      formation of bone or to produce a phagocytic tissue response. Only when the
      interface was unstable did a fibrous membrane form, and only then in the presence
      of PE.

PMID- 12211692
TI  - Is titanium so bad?

PMID- 12211691
TI  - Effects of alumina and zirconium dioxide particles on arachidonic acid metabolism
      and proinflammatory interleukin production in osteoarthritis and rheumatoid
      synovial cells.
AB  - We describe a model which can be used for in vitro biocompatibility assays of
      biomaterials. We studied the in vitro response of human osteoarthritis or
      rheumatoid arthritis fibroblast-like synoviocytes to Al2O3 or ZrO2 particles by
      analysing the production of interleukin-1 (IL-1) and interleukin-6 (IL-6) and the
      metabolism of arachidonic acid via lipoxygenase and cyclo-oxygenase pathways. Our
      results show that, in these cells and under our experimental conditions, Al2O3
      and ZrO2 did not significantly modify the synthesis of IL-1 and IL-6 or the
      metabolism of arachidonic acid.

PMID- 12211693
TI  - Should slipped capital femoral epiphysis (SCFE), a misnomer, be renamed as
      idiopathic capital femoral physiolysis (ICFP).

PMID- 12211694
TI  - Supracondylar extension fracture of the humerus in children.

PMID- 12211695
TI  - Nineteenth century mercury: hazard to wading birds and cormorants of the Carson
      River, Nevada.
AB  - Contemporary mercury interest relates to atmospheric deposition, contaminated
      fish stocks and exposed fish-eating wildlife. The focus is on methylmercury
      (MeHg) even though most contamination is of inorganic (IoHg) origin. However,
      IoHg is readily methylated in aquatic systems to become more hazardous to
      vertebrates. In response to a classic episode of historical (1859-1890) IoHg
      contamination, we studied fish-eating birds nesting along the lower Carson River,
      Nevada. Adult double-crested cormorants (Phalacrocorax auritus), snowy egrets
      (Egretta thula) and black-crowned night-herons (Nycticorax nycticorax) contained
      very high concentrations of total mercury (THg) in their livers (geo. means 134.8
      microg/g wet weight (ww), 43.7 and 13.5, respectively) and kidneys (69.4, 11.1
      and 6.1, respectively). Apparently tolerance of these concentrations was possible
      due to a threshold-dependent demethylation coupled with sequestration of
      resultant IoHg. Demethylation and sequestration processes also appeared to have
      reduced the amount of MeHg redistributed to eggs. However, the relatively short
      time spent by adults in the contaminated area before egg laying was also a factor
      in lower than expected concentrations of mercury in eggs. Most eggs (100% MeHg)
      had concentrations below 0.80 microg/g ww, the putative threshold concentration
      where reproductive problems may be expected; there was no conclusive evidence of
      mercury-related depressed hatchability. After hatching, the young birds were fed
      diets by their parents averaging 0.36-1.18 microgMeHg/g ww through fledging.
      During this four to six week period, accumulated mercury concentrations in the
      organs of the fledglings were much lower than found in adults, but evidence was
      detected of toxicity to their immune (spleen, thymus, bursa), detoxicating
      (liver, kidneys) and nervous systems. Several indications of oxidative stress
      were also noted in the fledglings and were most apparent in young cormorants
      containing highest concentrations of mercury. This stress was evidenced by
      increased thiobarbituric acid-reactive substances, low activities of enzymes
      related to glutathione metabolism and low levels of reduced thiols, plus an
      increase in the ratio of oxidized to reduced glutathione. At lower concentrations
      of mercury, as was found in young egrets, we observed elevated activities of
      protective hepatic enzymes, which could help reduce oxidative stress. Immune
      deficiencies and neurological impairment of fledglings may affect survivability
      when confronted with the stresses of learning to forage and the ability to
      complete their first migration.

PMID- 12211696
TI  - K-ras oncogene DNA sequences in pink salmon in streams impacted by the Exxon
      Valdez oil spill: no evidence of oil-induced heritable mutations.
AB  - It was hypothesized in previous studies that the Exxon Valdez oil spill in Prince
      William Sound, Alaska, induced heritable mutations and resulted in mortality of
      pink salmon (Oncorhynchus gorbuscha) embryos. In one of these studies, laboratory
      exposure of pink salmon embryos to crude oil resulted in apparent mutation
      induction in exon 1 and exon 2 of the K-ras oncogene, but no fish from the area
      impacted by the oil spill were analyzed. We assessed K-ras exon 1 and exon 2 DNA
      sequences in pink salmon from five streams that were oiled and five streams that
      were not oiled by the Exxon Valdez oil spill in Prince William Sound, and two
      streams with natural oil seeps and one stream without seeps on the Alaska
      Peninsula. Of the 79 fish analyzed for exon 1 and the 89 fish analyzed for exon
      2, none had the nucleotide substitutions representing the mutations induced in
      the laboratory study. Other variable nucleotides occurred in similar proportions
      in oiled and non-oiled streams and probably represent natural allelic variation.
      These data do not support the hypothesis that heritable mutations in the K-ras
      gene were induced by the Exxon Valdez oil spill or oil seeps.

PMID- 12211697
TI  - Toxic and feeding deterrent effects of native aquatic macrophytes on exotic grass
      carp (Ctenopharyngodon idella).
AB  - Declines of amphibians have been attributed to many factors including habitat
      degradation. The introduction of grass carp (Ctenopharyngodon idella) as a
      biological agent for aquatic plant control in ponds and lakes managed narrowly
      for human recreation has likely contributed to amphibian declines through massive
      plant removal and associated habitat simplification and thus degradation. This
      research examined the interactions among grass carp and three Midwestern aquatic
      plants (Jussiaea repens, Ranunculus longirostris, and R. flabellaris) that may be
      of value in rehabilitation of habitats needed by amphibians. The feeding
      preference study found that C. idella avoided eating both J. repens and R.
      longirostris. Ranunculus species studied to date contain a vesicant toxin called
      ranunculin that is released upon mastication. The study that compared the effects
      of R. flabellaris, J. repens and a control food administered by tube feeding to
      C. idella found significant lesions only in the mucosal epithelium of the
      individuals exposed to R.flabellaris. The avoidance by C. idella of J. repens and
      R. longirostris in the feeding preference study, and the significant toxicity of
      R. flabellaris demonstrated by the dosing study, indicate these plants warrant
      further examination as to their potential effectiveness in aquatic amphibian
      habitat rehabilitation.

PMID- 12211698
TI  - Effects of lead on 4-aminobiphenyl pharmacokinetics in liver, kidney, spleen,
      testes, heart, lung and hemoglobin adduct for rat model.
AB  - Lead affects almost every system in the body and 4-aminobiphenyl increases the
      incidence of bladder cancer among human exposed to aromatic amines, but little
      attention has been paid to the effects of lead (heavy metals) on the distribution
      and metabolic kinetics of 4-ABP (organic pollutants) in the organisms of the
      terrestrial ecosystems. In this study, male S.D. rats as model animals drinking
      tap water with and without lead with i.p. injection of 4-aminophenyl were used to
      study 4-aminobiphenyl pharmacokinetics with statistical analysis in three types
      of information systems: (1) hemoglobin adduct in the blood; (2) distribution
      concentrations in liver, kidney, spleen, testes, heart and lung; (3) relative
      weights of the six organs. Kinetic equations of 4-aminobiphenyl-hemoglobin adduct
      for two groups of rats drinking water with and without lead were all linear.
      Principal components were obtained based on three types of variants: (1) variants
      of distribution concentrations; (2) variants of relative weights; (3) variants of
      hemoglobin adduct, distribution concentrations and relative weights. Through a
      comparison of two groups of principal components, the result implied that lead
      changed 4-aminobiphenyl distribution kinetics in the six organs, had significant
      effects on the six organ relative weights, and had also significant effects on
      all thirteen variants as a whole. Correlation analysis of the principal
      components showed that lead could not significantly change the relation of
      hemoglobin adduct with time after dosing 4-aminobiphenyl. However, another result
      indicated that lead considerably improved the correlation between hemoglobin
      adduct and the thirteen variants as a whole. This implied that hemoglobin adduct
      could characterize all the thirteen variants as an index of 4-aminobiphenyl
      pharmacokinetics for the rats drinking water with lead, which conclusion was not
      suitable for the rats drinking water without lead. The research indicated that
      heavy metals existing in the organisms play an important role in the studies on
      pharmacotoxicology of organic pollutants. Frequently, various xenobiotics (heavy
      metals and organic pollutants) enter organisms simultaneously, therefore heavy
      metals should be considered comprehensively in the pharmacotoxicology of organic
      pollutants in animals in the terrestrial ecosystems theoretically and
      practically.

PMID- 12211699
TI  - Sublethal effects of exposure to chemical compounds: a cause for the decline in
      Atlantic eels?
AB  - Because of their unusual life cycle, American and European eels (Anguilla
      rostrata Lesueur and A. anguilla L.), are particularly exposed to pollutant
      effects. Because silver eels fast when they leave the freshwater system, the
      transoceanic migration forces them to constitute energy reserves in the form of
      muscle lipids, that are needed for successful spawning. Using species biological
      data, toxicological and ecotoxicological information, hypotheses are given to
      assess the contribution of pollution from freshwater sources to the recorded
      decline in the American and European eels fisheries since the 1980s. This paper
      first describes the lipid storage problems and the relative migratory capacities.
      Then several studies on the accumulation of xenobiotics in various anatomical
      compartments, on the biological half-lives of these compounds, and on their
      sublethal toxicity, are reviewed. During migration, lipid mobilization returns
      persistent lipophilic pollutants back into circulation, these being concentrated
      particularly in gonads at the crucial time of gametogenesis. Extrapolation of
      toxicological analysis (individual physiology) to the population level (spawning
      success) suggests that the quality of future spawners leaving freshwaters is one
      of the prime factors for the conservation of this threatened species.

PMID- 12211700
TI  - Solar UV radiation enhances the toxicity of arsenic in Ceriodaphnia dubia.
AB  - Extensive research exists regarding the toxicity of metals (including arsenic) to
      aquatic invertebrates. However, there has been little consideration of potential
      synergies between metals and ultraviolet (UV) radiation--despite considerable
      debate on this topic in human health research. Ultraviolet radiation is nearly
      ubiquitous in the natural environment, but it is generally overlooked as a
      confounding variable in toxicological assessments. We evaluate synergies between
      arsenic and solar UV radiation using the crustacean, Ceriodaphnia dubia. Both
      laboratory (with simulated solar radiation) and outdoor (with natural solar
      radiation) factorial experiments were performed with two intensities of UV (low
      and high) and four arsenic concentrations (0, 1, 1.25 and 1.5 mg/l). The
      laboratory experiment was multigenerational, examining survival and fecundity
      effects. The combination of high UV + 1.5 mg/l As adversely impacted survival;
      whereas, High UV + 0 mg/l As and Low UV + 1.5 mg/l As treatments did not. These
      results suggest synergism. This pattern was consistent for all three generations.
      Fecundity effects were not consistent across generations, and arsenic was
      demonstrated to have a greater impact than UV. Outdoor experiments were limited
      to assessing survival. Exposures in September 1999 resulted in a pattern similar
      to that in the laboratory exposure. High UV + 1.5 mg/l As treatment elicited
      diminished survival as compared to high UV + 0 mg/l As and low UV + 1.5 mg/l As.
      These results indicate that a synergistic effect between arsenic and UV exposure
      is possible under ambient conditions and within a relatively narrow dose range.
      The mechanism of this effect is unknown but could include synergistic genotoxic
      or oxidative stress. These findings point to the importance of using realistic UV
      exposures when determining criteria for protection of aquatic life.

PMID- 12211701
TI  - Damage to extrahepatic bile ducts during laparoscopic cholecystectomy--own
      experience.
AB  - In the years 1991-2000, 6873 patients were operated at the Department of General,
      Oncological and Thoracic Surgery in Central Medical Hospital in Warsaw, due to
      cholecystolithiasis. Extrahepatic bile ducts were damaged in 9 patients. These
      lesions included: pointed damage with electrocoagulation, bile duct incision or
      sectioning and the resection of the main stem of bile duct. In 7 patients, the
      lesions were diagnoses intraoperatively and the conversion was performed. Two
      patients required laparotomy at later stage. As complications developed, some
      patients required relaparotomy. Two patients died due to multiorgan failure. The
      injury of extrahepatic bile ducts remains a dangerous, potentially life
      threatening complication of cholecystectomy, irrespective of the operative
      technique applied.

PMID- 12211702
TI  - Immunological abnormalities in children with biliary atresia.
AB  - Since orthotopic liver transplantation is the treatment of choice for bilary
      atresia, the role of nutritional support preceding this procedure is significant.
      The aim of this study was to assess the selected parameters of both humoral and
      cellular immunity before and after nutritional support. Eight children aged 1.08
      7 years. with biliary atresia, qualified to LTx, received high-calorie standard
      diet supplemented with MCT oil. The distribution of functionally different
      lymphocyte subpopulations in the peripheral blood was evaluated using double
      color flow cytometry (EPICS-MCL, Coulter). The concentrations of total serum
      immunoglobulins were measured by nephelometry (Beckman Array 360) and
      concentrations of IgG subclasses by ELISA. Abnormalities in the expression of
      lymphocyte surface markers as well as in immunoglobulin synthesis were as
      follows: 1) decrease in the percentage of total CD3+ (4/8), CD4+ (5/8), CD8+
      (3/8) cells and markedly elevated percentage of CD19+ B cells (4/8); 2) reduction
      of the proportion of 'naive' CD4+ and CD8+ lymphocytes but normal percentage of
      'memory' CD4+ and CD8+ cell subsets; 3) hypergammaglobulinemia with especially
      high levels of IgG (16.0-3.05 g/l) and IgA (2.6-6.66 g/l) was found in 6 out of 8
      children. Treatment with hypercaloric diet did not improve the immunological
      parameters. We conclude that lymphopenia and possibly also hypergammaglobulinemia
      observed in BA children resulted mainly from the deficiency of the so-called
      'naive', suppressor-inducer CD4+ T cell subset (CD4+/CD45RA+) that is known to
      maintain the proper level of immunoglobulin synthesis by inhibition of B cell
      differentiation into plasma cells.

PMID- 12211703
TI  - Hepatobiliary scanning in the diagnosis of biliary atresia.
AB  - Early diagnosis is vital in the neonatal cholestasis. The aim of this study was
      to assess the usefulness of hepatobiliary scanning in the diagnosis of biliary
      atresia. 33 hepatobiliary scannings performed in 30 children with cholestasis
      over the last two years were analysed. The mean age at the diagnosis was 6.6
      weeks. The investigation was carried out with Multispect camera using intravenous
      infusion of 99mTc-MBrIDA. In 23 patients there was no passage of the
      radiolabelled substance into the intestinal tract. In 18 patients biliary atresia
      was diagnosed. One patient with a clinical suspicion of Alagille syndrome had two
      scannings performed at the interval of two weeks. In 1 child a common biliary
      tract cyst with total obstruction of extrahepatic biliary tree was diagnosed. In
      18 children with biliary atresia the diagnosis was confirmed during the operation
      and Kasai procedure was performed. In 2 children the second scanning showed bile
      drainage. In 3 children intrahepatic cholestasis was diagnosed in addition to the
      bile passage failure. Hepatobiliary scanning in the diagnosis of neonatal
      cholestasis was characterised by high sensitivity (100%) but lower specificity
      (75%). In difficult cases the final diagnosis should be made on a basis of
      complex clinical, biochemical and radiological techniques and, if necessary, it
      should be verified by intraoperative cholangiography.

PMID- 12211704
TI  - Value of magnetic resonance cholangiography (MRC) in primary sclerosing
      cholangitis (PSC).
AB  - BACKGROUND: Magnetic resonance cholangiography is a relatively new method, hence
      it has not gained a proper status yet in the diagnostic algorithm in patients
      with bile duct diseases. Many authors believe that MRC is an effective method for
      the visualisation of bile ducts. The aim of the study is to evaluate MRC
      usefulness in patients with PSC. MATERIAL AND METHODS: The study material
      consisted of 4 patients with PSC (3 men and 1 woman) aged 23-50 years. Patients
      were subjected to liver MRI in transverse plane, and T1 and T2-weighted images
      were obtained. Additionally, magnetic resonance cholangiography was performed
      with Gyroscan 0.5 T unit and Magnevist contrast medium. RESULTS: The patients
      manifested cholestasis and hepatitis of different duration (range: 2-14 years).
      The biochemical analyses revealed FA ranging from 563 to 1114 IU/l, GGTP 157-1270
      IU/L, AlAT 56-295 IU/L, AspAT 80-190 IU/L. Three out of four patients displayed
      significant increase in the level of ANCA antibodies. Histopathological
      investigation of the liver, conducted in 3 out of 4 patients, showed cholangitis
      et pericholangitis. ERCP was attempted in all the patients. In one case,
      irregular, overlapping and narrowed bile ducts were found, while in two cases it
      was impossible to fill intrahepatic ducts. ERCP was not performed due to
      technical obstacles encountered in one patient. All the subjects underwent MRC.
      In three cases, the segmental irregular dilatation of intrahepatic ducts was
      observed, while in one case intrahepatic ducts were poorly marked. The defect in
      the filling of initial segment of common bile duct was diagnosed in one patient.
      Another patient had a lesion adjacent to common bile duct--low signal intensity
      in T1 and the intensification after the administration of contrast medium
      indicate the presence of expansive process. CONCLUSIONS: 1. MRC is an accurate
      examination enabling the visualisation of all bile ducts in their natural size.
      2. Simultaneous MRI of the liver allows for the diagnosis of focal lesions. 3.
      MRC may be used in those cases, where ERCP cannot be performed for technical
      reasons or when it is objected by the patient.

PMID- 12211705
TI  - Nasobiliary drainage for biliary leaks after laparoscopic cholecystectomy.
AB  - BACKGROUND: The optimal endoscopic procedure and the appropriate duration of
      treatment in management of patients with biliary leaks after laparoscopic
      cholecystectomy (LC) have not been established so far. The aim of the study is
      the evaluation of endoscopic drainage by endoscopic sphincterotomy (ES) and/or
      nasobiliary tube placement in treatment of biliary leaks after LC. MATERIAL AND
      METHODS: ERCP identified a biliary fistula site after LC in 17 patients as
      arising from the cystic duct stump (n = 12), anomalous branch of right hepatic
      duct (n = 1) and common bile duct (n = 4). The mean time from LC to referral was
      7.5 days. Therapy consisted of insertion of 7F-nasobiliary tube without ES in 13
      patients and with ES in 4 patients. ES was performed only in cases of common bile
      duct injury. Nasobiliary tubes were used in all patients because this allowed for
      frequent contrast examinations in order to monitor efficacy of therapy and to
      determine the exact duration of treatment required. RESULTS: Nasobiliary tube
      placement alone was effective for the treatment of biliary leaks after LC in all
      patients, except 4 patients with common bile duct injury. Nasobiliary tube alone
      is not as effective for drainage of this part of the biliary tree as the
      combination of ES with nasobiliary tube. All leaks closed within 1 week, except
      for four patients with common duct leaks in whom 2 weeks were required for
      closure of the fistula. CONCLUSION: Nasobiliary tube placement is effective in
      healing biliary leaks after LC. I prefer to avoid ES because of its procedure
      related risk. ES was performed only in cases of common bile duct injury in order
      to reduce the resistance to normal bile to a minimum.

PMID- 12211706
TI  - Percutaneous treatment of malignant bile duct strictures in patients treated
      unsuccessfully with ERCP.
AB  - BACKGROUND: The preferred treatment of malignant distal bile duct strictures is
      endoscopic stent insertion. When this fails, percutaneous drainage is an
      alternative to surgery. The purpose of this study was to evaluate the success and
      complication rate of temporary percutaneous treatment. MATERIAL AND METHODS: 20
      patients (12 men, 8 women, mean age 62 years) with obstructive jaundice secondary
      to pancreatic carcinoma (14 patients), metastases of colorectal carcinoma (3
      patients) and cholangiocarcinoma (3 patients) underwent percutaneous treatment
      after 2 unsuccessful attempts of endoscopic cannulation. Puncture of the
      intrahepatic bile duct system was done under US and direct radiological
      monitoring using a 22-gauge needle. RESULTS: In 11 patients bile was drained
      internally-externally using multiple side holes catheters placed percutaneously
      via the bile ducts and Vater's papilla into the duodenum. In 4 patients bile was
      drained internally by percutaneous stent insertion. In all other patients bile
      was drained externally. The internal-external bile drainage was temporary. 14
      days after this procedure in all patients endoscopic sphincterotomy was performed
      and endoprosthesis was placed. In the group with percutaneous internal bile
      drainage further endoscopic treatment was successful in 2 patients and in
      remaining patients the next stent had to be inserted percutaneously. In the group
      with percutaneous external bile drainage stent placement during ERCP was possible
      in 2 patients. The overall success rate for bile drainage was 100%. In 15
      patients (75%) further endoscopic retrograde procedures were thus made possible.
      Complications occurred in 2 of the 20 patients (10%). None were life-threatening
      and surgical intervention was not necessary. One patient developed cholangitis
      and one another--bacteraemia. CONCLUSION: Temporary, percutaneous bile drainage
      is an alternative with a high success rate when endoscopic cannulation fails.
      Surgery can be avoided in nearly 75% of cases.

PMID- 12211707
TI  - Carcinoma adenoides cysticum as a primary neoplasm most probably derived from
      biliary ducts--case report.
AB  - Adenoid cystic carcinoma is a typical tumor of large and small salivary glands
      and sometimes of the breast. The aim of this report is presentation of a case of
      primary liver cancer with adenoid cystic cancer histology in 21-year old female
      patient. The tumor was discovered accidentally during pregnancy. The patient did
      not complain of any ailments. In biochemical tests only slightly elevated
      bilirubin, alkaline phosphatase and GGT concentrations were observed. No focal
      lesions in other organs were found in imaging examinations. Huge tumor of 30-cm
      diameter was found during surgery, encompassing almost whole left and right lobe
      of the liver. The biopsy taken from the tumor revealed histological picture
      typical for adenoid cystic carcinoma. Additional stainings and
      immunohistochemical examinations pointed to biliary ducts as possible place of
      origin of the neoplasm. SUMMARY: Among primary liver tumours of atypical clinical
      course the possibility of adenoid cystic carcinoma, deriving most probably from
      the biliary ducts, should be considered.

PMID- 12211708
TI  - Prognostic factors in the treatment of chronic hepatitis B with interferon alpha
      in children.
AB  - One hundred children with chronic hepatitis B, aged 1-17.3 years participated in
      the study. The results of treatment with interferon alpha (IFN-alpha) were
      evaluated. An attempt was made to define the factors predicting positive response
      to treatment. Three million units of IFN-alpha 2a or 2b were given by
      subcutaneous injections to analysed patients 3 times a week for 20 weeks.
      Positive treatment outcome reflected in HbeAg elimination was observed in 46% of
      children. High AlAT activity preceding therapy had a statistically significant
      effect on positive treatment outcome. The inhibition of HBV replication caused by
      the treatment was permanent and it coexisted with the normalisation of AlAT
      activity in blood serum. Full response to therapy with IFN-alpha measured with
      the elimination of HbeAg and HbsAg was observed in 14% of children. It was
      favoured by high AlAT activity before treatment and short HBV duration.

PMID- 12211709
TI  - Correlation of morphological alterations of light and electron microscopy in
      chronic type B and C hepatitis.
AB  - Chronic type B and C hepatitis involves inflammatory lesions of a variable
      intensity and variably advanced fibrosis. Considering current, progressively
      growing requirements for correct evaluation of lesions in liver biopsies, an
      attempt was made to appraise suitability of selected techniques for a broadened
      histopathological diagnosis. The lesions were evaluated at the level of light and
      electron microscopy. Material for the study consisted of liver biopsies obtained
      from adults and children (n = 60) with serological markers of chronic type B or
      type C hepatitis. Routine techniques of staining for light and electron
      microscopy, as well as the techniques of Brachet and Feulgen, were applied. HBcAg
      expression and HBV-DNA detection in children with chronic type B hepatitis were
      studied employing the avidin-biotin peroxidase complex (ABC) technique and in
      situ hybridisation with the ImmunoMax signal amplification. Slight or moderately
      intense inflammatory lesions (grading of 1 to 2 points) and a low level of
      fibrosis advancement (staging of 1 to 2 points) prevailed in the material,
      independently of the etiologic agent involved and age of the patient. Both in
      children and in adults, extensive lesions in the nuclear chromatin represented
      the common trait of chronic type B and type C hepatitis examined by light
      microscopy. Ultrastructural patterns confirmed the lesions and demonstrated virus
      resembling particles in the cell nuclei. In HCV infection, hepatocyte cytoplasm
      contained tubular and horseshoe-shaped structures with lesions of mitochondria,
      while in HBV infection Dane's particles and tubular forms of HBsAg were detected.
      For cognitive reasons and due to frequently equivocal literature data, our data
      on ultrastructural lesions in chronic type C hepatitis seem to be of particular
      interest. Using the ImmunoMax signal amplification, we were able to diagnose HBV
      infection under light microscope and to define stage of the infection. Their
      sensitivity, specificity and relatively short time required for performing the
      tests makes them advisable in the routine diagnosis of the two infections.

PMID- 12211710
TI  - Evaluation of HBV and HCV antigens expression in correlation with HBV DNA and HCV
      RNA occurrence in liver biopsy specimens of patients with chronic hepatitis type
      B and chronic hepatitis type C, respectively.
AB  - MATERIAL AND METHODS: The material studied consisted of single liver biopsy
      specimens and serum samples from 97 patients diagnosed by clinical and
      serological criteria as having chronic hepatitis of either type B (38 patients
      seropositive for HBsAg) or type C (59 patients seropositive for anti-HCV).
      Diagnosis of chronic hepatitis, including grading and staging of the process, was
      established by histopathological examination of routinely stained serial paraffin
      sections. The expression of HBV and HCV antigens was detected in frozen sections
      by amplified immunoperoxidase method (EnVision, DAKO) with the use of monoclonal
      anti-HBs antibodies (DAKO), polyclonal anti-HBc antibodies (Biogenex) and FITC
      labeled human antibodies to HCV antigens. HBV DNA and HCV RNA were searched for
      in tissue homogenates with PCR (In Gen; Terpol, Sieradz) and RT PCR (Cobas
      Amplicor HCV RNA, Roche), respectively. RESULTS: HBsAg was detected in all and
      HBcAg in 26 of the 38 biopsy specimens with chronic hepatitis type B from
      patients who were seropositive for HBsAg and anti-HBc, and for either HBeAg (25
      cases) or anti-HBe (13 cases). HBV DNA was identified in 32 out of 38 liver
      biopsy specimens. Out of the 32 HBV DNA positive specimens, 6 that had been
      obtained from patients seropositive for anti-HBe, lacked HBcAg expression. HCV
      antigens were found in 27 (50%) out of 54 specimens which showed the presence of
      HCV RNA. CONCLUSIONS: These results are indicative for a strong positive
      correlation between the expression of HBV antigens and that of HBV DNA in liver
      biopsy specimens. The detection of HCV antigens has proved to positively
      correlate with that of HCV RNA in 50% of the specimens examined. It appears,
      therefore, that testing of liver biopsy specimens for HBV and HCV antigens may,
      in a significant proportion of cases, extend the histopathological diagnosis as
      to include identification of the etiologic factor.

PMID- 12211711
TI  - Short-term changes of serum IL-2 and IL-6 induced by interferon alpha-2b in
      patients with chronic hepatitis C.
AB  - BACKGROUND: The standard therapy of chronic hepatitis C with interferon alpha
      (IFN alpha) and ribavirin has established but limited efficacy. The prognostic
      factors of treatment are still under investigation. IL-2 and IL-6 are key
      cytokines involved in activation of B and T lymphocytes and thus in humoral and
      cellular responses; they are also deeply involved in generation and maintenance
      of inflammatory processes. The aim of the study was to evaluate the short-term
      influence of INF alpha-2b on serum IL-2 and IL-6 levels in sustained responders
      (SR) and non-responders (NR). MATERIAL AND METHODS: Altogether 12 patients (7
      males and 5 females) chronically infected with HCV (anti-HCV positive, HCV-RNA
      positive by PCR) were enrolled to the study. Patients were treated with IFN 3 MU
      tiw for 6 months and then they were followed for another 6 months. Five patients
      responded to the treatment (sustained responders-SR)-Group I, seven patients did
      not respond (non-responders-NR)-Group II. Serum concentrations of IL-2 and IL-6
      were assessed by ELISA before ['0'] and at 1st ['1'], 2nd ['2'], 3rd ['3'], 6th
      ['4'] and 12th ['5'] hour after the first IFN injection. CONCLUSIONS: Interferon
      alpha-2b induced short-term increase of serum IL-2 concentrations in SR but not
      in NR. Serum IL-6 level increased both in SR and NR but this effect was more
      pronounced and persisted longer in sustained responders.

PMID- 12211712
TI  - Interferon versus interferon and UDCA combined therapy in chronic hepatitis C.
AB  - BACKGROUND: Interferon alpha (IFN) has been shown to have established efficacy in
      the treatment of chronic hepatitis C but its effectiveness is unsatisfactory.
      Combined therapies with IFN and other antiviral or immunomodulatory drugs are
      under evaluation. A combination of interferon alpha and ursodeoxycholic acid UDCA
      has been reported to give better results than interferon alone. The aim of the
      study was to assess the efficacy of IFN monotherapy versus IFN and UDCA therapy
      in patients with chronic hepatitis C. MATERIAL AND METHODS: We studied 38
      patients (25 males and 13 females) chronically infected with HCV (anti-HCV
      positive, HCV-RNA positive by PCR). Seventeen of them were treated with IFN 3 MU
      tiw for 6 months--Group I. The remaining 21 patients were treated with IFN, at
      the same dosage, plus UDCA (10 mg/kg/day) also for 6 months--Group II. Patients
      were followed for 6 months. 6 months after the end of therapy, laboratory
      biochemical parameters, HCV viremia and proportion as well as time to relapse
      were assessed. CONCLUSIONS: In contrast to previous reports we did not find any
      differences neither in proportion of HCV reactivation nor in the time of its
      appearance among patients treated because of chronic hepatitis B with IFN alone
      or with IFN plus UDCA combined therapy. We also did not find any difference in
      initial and late response to the treatments in both groups.

PMID- 12211713
TI  - Epidemiology of hepatitis C virus infections in children.
AB  - BACKGROUND: Epidemiological analysis of hepatitis C virus infections in children
      diagnosed and treated in the Hepatology Outpatient Clinic in Bytom between 1996
      and 1999. MATERIAL AND METHODS: The study comprised 62 children with detected
      serum presence of anti-HCV antibodies (ELISA method) and/or HCV-RNA (RT-PCR
      method). Risk factors for the infection were thoroughly analysed on the base of
      questionnaires. RESULTS: It was established that in 55 (88.7%) children high
      probability of infection existed in connection with past hospitalization and
      applied diagnostic and therapeutic procedures, such as: transfusion of blood and
      its preparations (24.19%), surgical procedures (22.58%), hospital treatment
      without invasive procedures and blood transfusions (19.35%). Familial exposure
      was a risk factor in 4.84% of cases, while in 6.45% of cases there were no
      burdens in the history. CONCLUSIONS: 1. In the evaluated group of children HCV
      infection was iatrogenic in character in majority of cases. 2. Hospitalization,
      even without invasive procedures, may be an important risk factor for HCV
      infection. 3. Familial exposure seems to be of secondary importance in
      transmission of HCV infection.

PMID- 12211714
TI  - Influence of HBV or HCV associated chronic liver diseases on the course and
      outcome of purulent, bacterial meningoencephalitis.
AB  - BACKGROUND: Aim of the study was evaluation of HBV or HCV associated chronic
      liver diseases (HBV or HCV CHLD) influence on the course and outcome of purulent,
      bacterial meningoencephalitis (PBME), without symptoms of sepsis. MATERIAL AND
      METHODS: Between 1995-99 there were 8 patients with PBME, with chronic HBV (5
      subjects) or HCV (3 subjects) infection, treated in our centre; mean age 43
      years. Str. pneumoniae and N. meningitidis were etiologic factors of PBME in 25%
      and 12.5% of patients, respectively. In 62.5% of cases etiology of PBME remained
      unknown. In 2 patients HBV or HCV CHLD was diagnosed before PBME (1 case--chronic
      active hepatitis, 1 case--postinflammatory liver cirrhosis). During
      hospitalization due to PBME in 4 patients liver cirrhosis was diagnosed on the
      base of clinical picture and laboratory results, in 2 patients chronic hepatitis
      B or C was subject to further diagnostic procedures. RESULTS: In 7 subjects
      (87.5%) significant increase of AlAT and AspAT activity was recorded during acute
      phase of neuroinfection as compared to results preceding the hospitalization (to
      300-400 U/l). Together with recovery from PBME decrease of aminotransferases
      activity was noted. In 1 fatal case high AlAT and AspAT activity was observed for
      the whole time of the disease. In 2 other patients with liver cirrhosis,
      classified into class A of Child-Turcott-Pugh classification at the beginning of
      PBME, after transient insignificant aminotransferases increase sudden
      decompensation of liver functions during recovery from PBME was observed. Both
      patients died due to haemorrhage from esophageal varices. In all patients with
      PBME and HBV or HCV CHLD inflammatory parameters of cerebrospinal fluid were
      increased for longer than average time. It was the reason of longer hospital
      stay. The influence of HBV or HCV CHLD on PBME outcome was not observed.
      CONCLUSIONS: 1. In patients with PBME concomitant HBV or HCV CHLD may exert
      negative influence on the course of neuroinfection and extend the period of
      hospitalization. 2. The increase of aminotransferases activity in these patients
      may suggest other hepatotropic virus superinfection and require further
      diagnostics. 3. In the case of HBV or HCV associated postinflammatory liver
      cirrhosis PBME may be connected with rapid liver disease progression and even the
      death of a patient.

PMID- 12211715
TI  - Autoimmune reactions in HBV and HCV.
AB  - BACKGROUND: Hepatotropic viruses HBV and HCV are capable of triggering autoimmune
      reactions (AIH). The aim of the study was the assessment of clinical course of
      AIH in patients with HBV and HCV, and the revision of treatment methods employed
      in these cases. MATERIAL AND METHODS: Among 120 patients with AIH and those
      qualified for antiviral therapy, 21 (17.5%) subjects were selected, including 16
      with HCV (7 men and 9 women) and 5 with HBV (including 2 men and 3 women). AIH
      diagnosis was based on international criteria taking into account biochemical
      tests, autoantibodies and morphological picture of the liver. HBV infection was
      confirmed with the determination of HBV markers and HCV--with the presence of
      antiHCV and HCV RNA. RESULTS: The duration of infection at AIH diagnosis was
      difficult to assess in patients with HCV. AIH was diagnosed when patients were
      qualified for antiviral treatment. Three patients displayed high anti-LKM1, 8-
      ANA and SMA, two pts--ANA, two pts--SMA, one pt--ANA + pANCA and one--SMA +
      pANCA. Nine patients did not show hyperproteinaemia, and hypergammaglobulinaemia
      was not observed in 2 patients. Six patients suffered from other immunity
      disorders--thrombocytopenia, vasculitis, arthritis, visceral lupus erythematosus.
      The diagnosis of chronic hepatitis was confirmed by morphological examinations in
      15 patients. Ten subjects received adrenocortical hormones, 3 patients were
      treated with adrenocortical hormones and azathioprine, 4 received interferon and
      3 received no treatment. All patients with HBV proved HBeAg(-). In these
      patients, AIH symptoms developed 5-18 years after the diagnosis of HBV infection.
      Liver biopsy confirmed the diagnosis in 4 patients. SMA was observed in 2
      subjects, ANA and SMA--in the remaining patients. All the subjects manifested
      typical biochemical changes as well as high IgG values. Extrahepatic exponents of
      immune process were observed in 3 patients. Three subjects were treated with
      Encorton (Prednisone), while 2 patients received Encorton and Azathioprine.
      CONCLUSIONS: Patients with HBV and HCV infections may manifest the features of
      AIH in the course of the disease, which requires careful attention while
      selecting treatment.

PMID- 12211716
TI  - Bcl-2 antigen expression in patients with chronic hepatitis C and advanced
      fibrosis.
AB  - Bcl-2 antigen is a proto-oncogene responsible for the inhibition of the death of
      cells in the mechanism of apoptosis. The expression of bcl-2 antigen was analysed
      in liver bioptates obtained from patients with chronic hepatitis C. Thirty-five
      patients with advanced fibrosis (bridging fibrosis or cirrhosis) and various
      inflammatory activity were investigated. Control group was formed of the subjects
      with minimum or non-existent fibrosis. Histological and immunohistochemical
      assessments were performed with the use of widely-acceptable methods. The
      expression of bcl-2 antigen within portal spaces and lobules was evaluated. The
      values of lobular index declined as the fibrosis increased. As far as portal
      space index is concerned, no significant changes in correlation with fibrosis
      advancement were noticed. Additionally, the expression of bcl-2 antigen was
      recorded within lymphocyte infiltrations in lobules and portal spaces, in the
      epithelium of bile ducts in portal spaces and proliferating bile ductules in
      lobules as well as in perisinusoid cells. In hepatocytes, bcl-2 expression was
      detected more often among controls than in the analysed patients. The expression
      of bcl-2 antigen is directly proportional to the degree of inflammatory activity
      and it is inversely proportional to the degree of fibrosis. It seems that
      positive colour reaction with bcl-2 antigen in lobules may be of prognostic value
      for the prediction of collagen fibroplasia development. Bcl-2 expression in
      portal spaces has a limited diagnostic value for the prediction of the scope of
      fibrosis in patients with chronic hepatitis C.

PMID- 12211717
TI  - Porphyria cutanea tarda, hepatitis C virus and selected symptoms of cholestasis.
AB  - BACKGROUND: The influence of hepatitis C virus (HCV) infection on the development
      of porphyria cutanea tarda (PCT) was recently detected, but the status of trace
      elements in etiology of the diseases is relatively poorly recognized.
      Individually observed symptoms of cholestasis do not seem to be related to the
      above conditions. MATERIAL AND METHODS: A group of 22 PCT patients (37-73 years
      old, mean 54.9 years), including 10 cases (45.5%) of serum HCV-RNA positive, as
      evaluated by automatic Cobas AmplicorTM Hepatitis C ver. 2.0 assay (Roche
      Diagnostics), was assessed. None of the patients have recently abused alcohol.
      Serum levels of copper and bilirubin, activity of gammaglutamyltranspeptidase
      (GGTP) and alkaline phosphatase (ALP) were measured in all patients. RESULTS: We
      have found statistically significant differences between both mean serum activity
      of GGTP (145.9 U/l vs. 58.3 U/l, p = 0.004) and mean serum copper levels (131.9
      mg/dl vs. 79 mg/dl, p = 0.003) in patients infected with HCV compared to the
      other PCT patients, respectively. Mean serum ALP activity was also higher, but
      the difference was not of statistical importance (106.9 U/l vs. 90.9 U/l, p =
      0.24); mean serum bilirubin concentration was significantly lower in HCV-infected
      patients (0.55 mg/dl vs. 0.85 mg/dl, respectively, p = 0.035). CONCLUSION: In our
      group of PCT patients we have noticed a higher serum copper level and higher
      activity of both GGTP and alkaline phosphatase, but lower level of serum
      bilirubin in patients infected with HCV as compared with those not infected. This
      observation does not confirm suggestions concerning the role of HCV in promotion
      of cholestatic liver disease in PCT patients. The influence of HCV infection on
      the metabolism of copper and GGTP activity is connected rather with the
      inflammatory lesions in the liver of PCT patients infected with HCV. Bilirubin
      metabolism in PCT patients requires further studies for its elucidation.

PMID- 12211718
TI  - Influence of hepatitis C virus (HCV) infection on porphyrin and iron metabolism
      in porphyria cutanea tarda (PCT) patients.
AB  - BACKGROUND: Porphyria Cutanea Tarda (PCT) is the most common form of porphyria.
      It is characterised by lowered activity of uroporphyrinogen decarboxylase. It
      seems possible that the hepatitis C virus (HCV) infection triggers the symptoms
      of PCT. MATERIAL AND METHODS: A group of 29 PCT patients (33-73 years old, mean
      54 years) was evaluated. In these patients the serum HCV-RNA (by mean of
      automatic Cobas AmplicorTM Hepatitis C ver. 2.0 assay, Roche Diagnostics),
      activity of transaminases (ALT, AST), serum protein fractions, iron, total iron
      binding capacity (TIBC), ferritin, transferrin, transferrin saturation, and
      urinary porphyrins excretion were assessed. RESULTS: The presence of HCV-RNA was
      detected in 12 cases (41.4%). Statistically important differences between
      currently HCV infected patients and other PCT patients concerned the following
      parameters: mean body mass (68.5 vs. 78.0 kg, p = 0.02), mean body mass index
      (22.4 vs. 26.8 kg/m2, p = 0.007), mean serum activities of ALT (112.6 vs. 65.4
      U/l, p = 0.02) and AST (85.0 vs. 56.5 U/l, p = 0.038), total serum protein
      concentration (78.0 vs. 71.6 g/l, p = 0.016) and serum alpha-2 protein
      concentration (7.2 vs. 5.5 g/l, p = 0.009), respectively. Some other not
      significant differences were also found: mean serum iron level 182 vs. 169
      micrograms/dl, transferrin concentration 2.77 vs. 2.56 g/l, transferrin
      saturation 43 vs. 45%, serum TIBC 445 vs. 397 mg/dl and ferritin concentration
      394 vs. 400 micrograms/l, respectively. The mean urinary uroporphyrin
      concentrations were 643 micrograms/l vs. 366 micrograms/l (p = 0.16) and those of
      coproporphyrins were 190 micrograms/l vs. 136 micrograms/l (p = 0.37),
      respectively. CONCLUSION: In the group of PCT patients investigated no
      significant relationship between current HCV infection and iron or porphyrin
      metabolism was noted. Nevertheless, HCV infection significantly influences the
      symptoms of liver damage and seems to influence other metabolic parameters in PCT
      patients.

PMID- 12211719
TI  - HCV-RNA detection in liver bioptates--a comparison of automatic and 'home-made'
      protocols combined with a new procedure of HCV-RNA extraction.
AB  - BACKGROUND: For HCV-RNA detection in liver tissue a generally accepted reference
      method has not been established yet. Therefore, we have developed a procedure of
      HCV-RNA extraction from liver tissue and compared two methods of HCV-RNA
      detection. MATERIALS AND METHODS: A set of 32 liver biopsy specimens, obtained
      from chronically HCV infected patients, has been examined. At the time of biopsy,
      serum HCV-RNA was detectable in 20 patients in RT-PCR automatic Cobas AmplicorTM
      Hepatitis C assay, ver. 2.0 (Roche Molecular Systems, Inc, Pleasanton, CA, USA) 2
      serum samples were negative for HCV-RNA and 10 patients has not been tested.
      Liver tissue has been homogenized in the presence of CRSR-Green (Fast RNA Kit
      Green, Bio101, Inc, Vista, CA, USA) and a mixture of phenol/chloroform/isoamylic
      alcohol, using a FastPrep homogenizator (Bio101, Inc, Vista, CA, USA). Then RNA
      has been isolated from the material obtained using the Total RNA Prep Plus
      procedure (A&A Biotechnology, Gdansk, Poland). Presence of HCV-RNA was next
      tested by means either of 'home-made' nested RT-PCR procedure or the RT-PCR
      automatic Cobas AmplicorTM Hepatitis C assay, ver. 2.0. In case of an inhibition
      of PCR detected in the first run of automatic assay, both PCR procedures have
      been repeated. RESULTS: In 5 cases of automatic assay an inhibition of PCR
      reaction has been detected in the first run, the RT-PCR procedures has been then
      successfully repeated in the second run. The presence of HCV-RNA in the liver
      tissues was detected in a total of 22 cases (69%) by mean of automatic assay and
      in a total of 20 cases (63%) by means of 'home-made' RT-PCR procedure. Except for
      two cases of HCV-RNA positivity in a biopsy tissue, detected by means of
      automatic but not 'home-made' procedure, the results obtained employing the
      methods have been identical. In one serum HCV-RNA positive case, the presence of
      HCV RNA has not been detected in a liver tissue using both methods. CONCLUSIONS:
      Our procedure of RNA isolation combined either with automatic Cobas AmplicorTM
      Hepatitis C assay, ver. 2.0 or 'home-made' RT-PCR procedure may be useful for
      establishing presence of HCV-RNA in liver tissue. In this combination, the
      automatic assay seems to be more sensitive than the 'home-made' procedure.

PMID- 12211720
TI  - Effect of IFN-alpha on total haemolytic activity of CH50 complement system and
      C3, C4 levels in children with chronic hepatitis C.
AB  - BACKGROUND: The pathogenesis of chronic hepatitis induced by virus C as well as
      the mechanisms responsible for the elimination of this infection are still not
      fully understood. The course of HCV infection depends on the extent to which both
      specific and non-specific response is induced. One of the treatment methods
      applied in HCV is the use of IFN-alpha which has both antiviral and
      immunomodulatory activity. The knowledge of IFN-alpha effect on non-specific
      humoral response may be helpful in the choice of optimal strategy for HCV
      prevention and treatment. The purpose of the study was the assessment of total
      haemolytic activity of CH50 complements as well as C3 and C4 levels in children
      with chronic hepatitis C treated with IFN-alpha. MATERIAL AND METHODS: Sixty
      children aged 3-15 years with chronic hepatitis C were included in the study. The
      diagnosis was based on biochemical examinations, the presence of HCV RNA and
      histological investigations of the liver. The study group was divided into two
      subgroups of 30 children each. One subgroup was treated with subcutaneous
      recombined IFN-alpha (Intron A Schering Plough) at the dose of 3 MU 3 times a
      week for 6 months, while the other subgroup was a control. All the children
      underwent the assessment of total haemolytic activity of CH50 complement
      according to modified Mayer's technique as well as the concentration of its
      components C3 and C4 with turbidimetric method with the use of Behring reagents
      and Turbi Time system. The assessments were performed at the beginning of the
      study and 6 months later. RESULTS: Total haemolytic activity of CH50 complement
      and C3, C4 levels after 6 months of IFN-alpha therapy were significantly higher
      in children on IFN-alpha when compared to control group. Among children treated
      with IFN-alpha, 9 managed to eliminate HCV genetic material from blood serum.
      Mean values of analysed parameters did not differ at both stages of the study in
      the IFN-alpha group between the children with and without HCV RNA elimination.
      CONCLUSIONS: Higher total haemolytic activity of CH50 complement and C3, C4
      levels after 6 months of treatment with IFN-alpha administered to children with
      chronic hepatitis C suggest that IFN-alpha is capable of reducing complement
      activity.

PMID- 12211721
TI  - Autoimmune hepatitis in the course of chronic HAV--four year observation.
AB  - The paper presents a case of a 17-year-old girl with type 1 autoimmune hepatitis
      in whom biochemical, serological and histopathological markers of chronic
      hepatitis A were observed for the last 4 years. The diagnosis was based on
      elevated levels of gammaglobulins, IgG and the presence of autoantibodies (ANA,
      SMA). At first, the patient was treated with the pulses of corticosteroids and
      then, as no improvement was observed, continuous steroid therapy was involved.
      Relatively mild clinical course of the disease and good response to treatment
      with prednisone were recorded. Our observations suggest that HAV is capable of
      inducing autoimmune reactions and they indicate possible development of chronic
      hepatitis A.

PMID- 12211722
TI  - Factors influencing natural history of chronic hepatitis C.
AB  - The aim of the study was to asses influence of selected epidemiologic and
      virusologic factors on the course of chronic hepatitis C (CHC). Data obtained
      from 550 CHC patients was analyzed (F/M: 241/309; age: 14-87, average age: 44.9
      +/- 15.6). HbsAg and HIV-positive, as well as patients taking drugs were excluded
      from the study. Progression of the liver disease was assessed by the maximal ALT
      activity, presence of clinical or histopathological symptoms of hepatic
      cirrhosis, and 363 liver biopsy results. Clinical and histological data was
      analyzed depending on: patients sex, age (= 40, and > 40 years old), portal of
      infection (history data on transfusion or another source of infection), history
      of HBV infection (presence or absence of anti-HBc antibodies), and HCV genotype
      (1b or no-1b group). HCV genotype was determined in 170 patients by the use of
      commercial InnoLipa kit (Innogenetics). Statistical analysis was based on t
      Student test and chi-squared test with or without Yates correction. It was proved
      that in patients over 40 years old or with history of transfusion inflammatory
      activity and liver fibrosis activity are significantly higher than in the rest of
      patients. More advanced age, transfusion and history of HBV infection are risk
      factors for hepatic cirrhosis development in CHC patients. Neither patient's sex
      nor HCV genotype were found to have significant influence on the course of CHC.

PMID- 12211723
TI  - DRB1 alleles in relation to severity of liver disease in patients with chronic
      hepatitis C.
AB  - The aim of our study was analysis of relation between HLA class II antigens and
      the liver disease severity in chronic hepatitis C (CHC) patients. The subject of
      analysis was data obtained from 134 CHC patients with disease confirmed by
      histopathologic test (F/M: 62/72; age 16-74; average age 41.4 +/- 12.7 yrs), HCV
      RNA-positive, HbsAg- and HIV-negative with no coexistence of any other liver
      diseases. Liver biopsy specimens were estimated according to Ishak's criterions
      (grading 0-18; staging 0-6). HLA DRB1 alleles were determined by a commercial
      method INNOLiPA DRB (Innogenetics, Belgium). Statistical analysis considered
      alleles occurring with frequency higher than 10%. The necroinflammatory activity
      (average grading score) was compared in groups of patients with- and without
      particular allele. The frequency of each allele's occurrence was analyzed
      according to patients sex, age and staging score of liver fibrosis. In
      statistical analysis t-Student test and chi-squared test with or without Yates'
      correction were applied. Statistically significant correlation was found between
      occurrence of DRB1*13 and DRB1*07 alleles and necroinflammatory activity
      intensification, and between occurrence of DRB1*13 allele and progression of
      liver disease. Mild liver damage, instead, expresses statistically significant
      relation with DRB1*11 allele.

PMID- 12211724
TI  - Thyroid gland dysfunctions during antiviral therapy of chronic hepatitis C.
AB  - BACKGROUND: The aim of this study was assessment of the frequency of thyroid
      dysfunctions (TD) during antiviral treatment of chronic hepatitis C (CHC).
      MATERIAL AND METHODS: Data obtained from 120 not treated before patients with
      CHC, confirmed by the liver biopsy, and with the correct initial thyroid
      function, was analyzed. 63 patients were treated with IFN-alpha, and 57 with IFN
      + ribavirin combined therapy. HCV genotype was determined in 80 patients, and
      alleles HLA DRB1 in 74. Both tests were carried out by the use of commercial
      assay InnoLipa (Innogenetics, Belgium). All the patients had TSH level regularly
      monitored every 4 weeks. If any abnormalities were observed, the whole set of
      tests was applied for diagnosis. Frequency of TD was analyzed according to
      patients' sex, therapy scheme, HCV genotype and HLA DBR1 alleles. Both groups,
      with TD and without TD were compared by the initial data, such as: patients' sex,
      age, ALT activity, and liver biopsy results. RESULTS: TD occurred in 40 patients
      (33.3%): in 7 (5.8%) signs of hypothyroidism, and in 33 (27.5%) hyperthyroidism.
      In 14 patients (11.7%) autoimmunological thyroiditis was diagnosed, in 2 (1.7%)
      subacute thyroiditis, and in the rest of patients only temporary changes in TSH
      concentration, without any clinical manifestations, were observed. In 4 women,
      the antiviral treatment was withdrawn, because of thyreotoxicosis, and in 6
      patients thyroid hormones supplementation was needed after termination of
      interferon application. Thyroid complications occurred significantly more often
      in women than in men. No significant differences according to the age, therapy
      scheme, ALT activity, fibrosis stage, nor HCV genotype were find in the TD
      frequency. Among 13 genotyped DRB1 alleles, differences were observed only in
      DRB*11 allele frequency: in 37.7% of patients with TD, and in 9.1% of patients
      without TD (p = 0.0093; Pc = 0.12). CONCLUSIONS: Antiviral treatment induces more
      often latent and transient thyroid dysfunctions as well as autoimmunological, and
      subacute thyroidis. The last mentioned complication may be the indication for
      withdrawal of the treatment, or may cause persistent hypothyroidism. Regular
      monitoring of TSH concentration, in 4-weeks intervals, seems to be essential for
      early diagnosis of thyroid complications.

PMID- 12211725
TI  - Assessment of HBV DNA levels in human plasma and peripheral blood mononuclear
      cells by TaqMan Q-PCR assay.
AB  - Hepatitis B virus DNA (HBV DNA) levels were quantitatively determined by a TaqMan
      quantitative polymerase chain reaction (TaqMan Q-PCR) in the plasma and in the
      peripheral blood mononuclear cells (PBMCs) of 120 patients with biopsy proven
      chronic hepatitis. The number of HBV DNA copies ranged from 10(1) to 10(10)/ml of
      the blood. There were no significant differences between plasma and PBMCs levels
      of HBV DNA in neither of HBV infected alone nor HCV co-infected patients. The
      number of HBV DNA copies was higher in the both compartments in blood of patients
      infected with HBV only, in comparison to those co-infected with HBV and HCV. In
      patients chronic hepatitis caused by both viruses (co-infection), decrease of HBV
      DNA copies in the PBMCs preceded its disappearance from the plasma. Our results
      suggest that assessment of HBV DNA in PBMCs does not produce important advantage
      in diagnosis of chronic hepatitis, and it seems to have the prognostic
      significance of positive outcome among the patients with chronic hepatitis
      induced by HBV and HCV co-infection. Our results also indirectly indicate that
      HCV may reciprocally inhibit replication of HBV.

PMID- 12211726
TI  - Increased AST and GGT activity as marker of RT-PCR inhibition in RNA extracts
      from peripheral blood.
AB  - The presence of HCV RNA in PMBC, with simultaneous absence of the virus in the
      plasma (7.8%), suggests that blood is better material for HCV RNA detection than
      plasma or serum in the diagnostic procedures of patients with chronic hepatitis C
      as well as in monitoring the antiviral therapy. We studied 111 patients with
      chronic hepatitis C (anti-HCV+) and elevated level of at least one biochemical
      marker: AST, ALAT, GGT, AP and bilirubin. Inhibition of amplification was 2% in
      plasma and 34% in whole blood samples. We applied modification of extraction to
      reduce the inhibitory effect on PCR, by introducing additional purification of
      the RNA extract in the Chomczynski method. After our modification of extraction
      was applied, inhibition was reduced to 1%. In attempt to identify such inhibitory
      markers that would label the samples, in which additional RNA extract
      purification should be applied, we analysed the activity of AST and ALAT enzymes,
      the key markers for parenchymal liver damage; GGT and AP, the markers for
      cholestatic hepatitis as well as bilirubin. We observed that the increased GGT
      and AST activities were correlated with the inhibition of RT-PCR. This
      correlation was statistically significant; for AST (Mann-Whitney test p = 0.09654
      and Kolmogorow-Smirnow test p = 0.01543) and for GGT (Mann-Whitney test p =
      0.02419 and Kolmogorow-Smirnow test p = 0.01921).

PMID- 12211727
TI  - Dynamics of HCV replication in patients with chronic hepatitis C during
      interferon and ribavirin combined therapy.
AB  - Objective of the present study was to determine the effect of combined therapy
      with interferon alfa-2b (3 MU; thrice weekly s.c.) and ribavirin (1200 mg daily
      p.o.) on the number of copies of positive and negative strands of the hepatitis C
      virus RNA (HCV RNA) in patients with biopsy-proven chronic hepatitis C. Number of
      copies of both strands was determined by a TaqMan reverse transcription
      quantitative polymerase chain reaction (TaqMan RT Q-PCR) in the whole blood
      before treatment, and 4, 12 or 24 weeks after introduction of the treatment.
      Before the treatment positive strand of HCV RNA was more frequently detectable
      and its level was higher compared to that of the negative strand. In several
      patients, we observed therapy-induced transient appearance or increase in the
      number of copies of the negative HCV RNA strand. As a result of 24-week
      treatment, the negative strand of HCV RNA was eliminated from the blood more
      effectively than the positive strand. Our results suggest that the assessment of
      dynamics of changes of the positive and negative strands levels of HCV RNA in
      interferon-naive patients with chronic hepatitis C may be useful in monitoring
      short-term effectiveness of combined antiviral therapy. They also indicate that
      TaqMan RT Q-PCR appears to be a valuable tool in monitoring the therapy in these
      patients.

PMID- 12211728
TI  - Does schistosomiasis interfere with application of Knodell score for assessment
      of chronic hepatitis C?
AB  - BACKGROUND: Schistosoma Mansoni (SM) is a significant etiology of liver disease
      in Egypt. Chronic hepatitis, predominantly HCV, is a major health problem
      worldwide. Whether, schistosomal affection could interfere with assessment of
      necroinflammatory injury and degree of fibrosis in liver biopsy of chronic
      hepatitis, is not a settled issue. The present study is an attempt to highlight
      this problem. MATERIAL AND METHODS: 185 individuals--pure schistosomal affection
      (25 pts), pure HCV (100 pts), and mixed schistosomal and HCV (HCV + SC) (60 pts)-
      were included. They were selected from among 222 biopsied patients with chronic
      liver disease attending the liver unit of Internal Medicine Department, Mansoura
      University July 1999-May 2000. They were subjected to rectal snip and serological
      test for schistosomiasis, liver functions, HBV, HCV serological markers, serum
      qualitative and quantitative PCR and liver biopsy. Masson trichrom stain was
      performed to assess fibrosis. Immunohistochemical staining for HBsAg & HBcAg were
      performed. Modified Knodell score was applied to assess the biopsy. RESULTS: Five
      out of the 25 pure schistosomal and only 2 of the mixed group revealed
      schistosomal granuloma. 30% and 33% of pure HCV and mixed patients, respectively,
      were found to be cirrhotic. No significant statistical difference was identified
      between the two groups with respect to necroinflammatory injury and Knodell score
      (p = 0.81). Additionally, no significant difference was identified related to the
      stage of fibrosis (p = 0.77). CONCLUSION: Schistosomal hepatic affection does not
      alter or interfere with assessment of necroinflammatory injury or fibrosis in
      mixed HCV-schistosomal liver affection.

PMID- 12211729
TI  - Acute haemolytic syndrome and liver failure as the first manifestations of
      Wilson's disease.
AB  - Acute liver failure and haemolytic syndrome appeared quite suddenly as the first
      manifestations of Wilson disease (WD) in five of our patients previously regarded
      as healthy persons (although an interview showed that 2-4 weeks prior to the
      illness the patients complained of several non-specific symptoms, such as
      abdominal pain, headaches, fever, weakness or behavioural changes). All the
      patients were young women (17-23 years), none of them had any history of liver
      disease. They were admitted with icterus, nausea, vomiting and symptoms of
      increasing haemolysis. The diagnosis of WD was given as disturbed copper
      metabolism. After a short period of observation ascites and anasarca occurred,
      haemorrhagic diathesis and other symptoms of liver failure increased. Levels of
      clotting factors decreased rapidly. Despite treatment with D-penicillamine,
      plasmapheresis, and symptomatic drugs, three of the women died in irreversible
      liver coma, due to the unavailability of liver transplantation. The fourth woman
      was carried to the Transplantation Centre, due to aggravation of the symptoms of
      liver failure, where liver transplantation was performed. Histopathologically
      micronodular cirrhosis was shown in all these cases. The fifth patient survived
      having undergone the above treatment without liver transplantation. The main
      differences between the patient who survived and those who died or underwent
      transplantation were relatively higher activity of alkaline phosphatase (26 U/l
      vs. 10-20 U/l), slightly higher levels of clotting factors and prothrombin time,
      which never fall below 68% of the control (versus 14-44% in other patients). Only
      in the surviving patient was the Kayser-Fleischer ring present. In four of our
      patients we found family members who were carriers of WD.

PMID- 12211730
TI  - Acute hepatic failure in alcoholic liver disease.
AB  - 296 patients with first clinical symptoms of alcoholic liver disease were
      hospitalized in Probationary-Infectious Diseases Department in Kielce, between
      1994-2000. In 52 (17.6%) of them, acute hepatic failure was diagnosed by
      detection of hepatic encephalopathy. Initial laboratory data of those patients
      who died (6.1%), and those who survived (11.5%) was compared. No statistically
      significant differences in analyzed parameters were found, except for
      significantly higher bilirubin concentration in the group of deceased. In both
      groups of patients, the frequency of hepatic failure complications, present at
      the admission to the hospital or those developed in the course of the disease,
      was also analyzed. The following complications were observed significantly more
      often in deceased: ascites, hepatorenal syndrome (HRS), spontaneous bacterial
      peritonitis (SBP), and gastrointestinal haemorrhage (GIH), while sepsis was
      similarly frequent in both groups.

PMID- 12211731
TI  - Scintiscanning in diagnostics of hepatopulmonary syndrome in children.
AB  - BACKGROUND: Arterial blood oxygenation disturbances accompanying liver cirrhosis
      are referred to as hepatopulmonary syndrome (HPS). HPS develops due to the
      formation of intrapulmonary arteriovenous shunts and dilatation of the vascular
      bed. The aim of the study was to assess the incidence of arteriovenous shunts in
      children with hepatic cirrhosis and HPS suspected on the basis of clinical signs,
      qualified for liver transplantation. MATERIAL AND METHODS: The study was carried
      out in a group of 21 children aged from 1.2 to 17.7 years (mean age 8.4); 8 girls
      and 13 boys. The patients were diagnosed as follows: biliary cirrhosis due to
      extrahepatic bile duct impatency--12, post-inflammatory liver cirrhosis due to
      infection with HVB--2, autoimmune hepatitis--2, fibrosis of the liver--2, alpha 1
      antitrypsin deficiency--1, progressive familial intrahepatic cholestasis--1,
      cystic fibrosis--1. The presence of arteriovenous anastomoses in the lungs was
      detected by scintiscanning utilizing microspheres (albumin macroaggregates).
      Under physiologic conditions, technetium-labeled microspheres injected i.v. are
      accumulated in pulmonary capillaries. Radioactivity detected in other organs
      (kidneys, brain) indicates the presence of pathologic shunts omitting the
      alveoli. A percentage ratio of radioactivity detected in the brain to that
      present in the lungs serves as the index of blood flow through the anastomosis
      (SI--shunt index). According to Grimon, the mean SI value for healthy children
      amounts to 0.43%, the values ranging from 1% to 2% are regarded as borderline
      ones, and those above 2% allow unequivocal diagnosis of HPS. RESULTS: The SI
      values obtained in the study ranged from 0.06 to 51%. In 7 patients SI exceeded
      1%, reaching 1.23% in one, and over 3% in the remaining 6 patients. No
      correlations were found either between SI value and the etiology of cirrhosis, or
      between the index and clinical condition of the patient assessed according to
      Child-Pugh scale. CONCLUSIONS: 1. Scintiscanning revealed the presence of
      arteriovenous shunts in the lungs of 6/21 (28.6%) investigated patients. 2. No
      correlation was found between the severity of HPS and the etiology and stage of
      the underlying disease.

PMID- 12211732
TI  - Do fibrinolytic proteins of human bile derive exclusively from gall bladder?
AB  - BACKGROUND: In this study we addressed the issue of whether fibrinolytic proteins
      are presented in gall bladder bile only or in choledochus bile as well. MATERIAL
      AND METHODS: Gall bladder bile was obtained from 20 patients (Group I) undergoing
      laparoscopic cholecystectomy. Bile from common bile duct was aspirated after
      insertion Kehr drainage from 9 patients (Group II). The concentrations of t-PA, u
      PA, PAI-1 and PAI-2 were measured by ELISA. RESULTS: We have shown that in
      cholecystectomized patients fibrinolytic proteins can be detected in bile both
      from gall bladder and from choledochus. Mean concentrations of t-PA, u-PA, PAI-1
      were lower in Group II (5.69 ng/ml vs 15.7; 0.46 ng/ml vs 0.7; 16.82 ng/ml vs
      26.16 ng/ml) or nearly equal for PAI-2 (343.53 ng/ml vs 341.02). All differences
      were insignificant (p > 0.05). CONCLUSIONS: Based on these results we concluded
      that the entire biliary tree produces the fibrinolytic proteins thus this
      production is not restricted to the gall bladder as it was earlier reported [1].

PMID- 12211733
TI  - Evaluation of acid gastric secretion with 24-hour pH-metry in patients with acute
      and chronic hepatitis induced by HBV.
AB  - BACKGROUND: Acute and chronic diseases of the liver often coexist with functional
      disorders and pathological changes in the stomach. Lavish data indicate greatly
      higher incidence of ulcerations and gastric erosions in patients with various
      hepatopathies. Due to considerable discrepancies in the assessment of acid
      gastric secretion, an attempt has been made to evaluate this phenomenon with 24
      hour pH-metry in patients with acute and chronic HBV. MATERIAL AND METHODS: The
      study material consisted of two equal groups of patients with dyspepsia--12
      subjects with acute HBV and 12 subjects with chronic HBV, as well as 15 healthy
      volunteers forming a control group. At enrollment, the patients over 65 years of
      age were excluded from the study as well as those with chronic diseases, with the
      history of surgery in gastrointestinal tract and the subjects treated with the
      medicines affecting gastric secretion. All the patients underwent pH-metry with
      the use of DL70 pH-meter with a glass electrode. Median pH (Me) and mean pH
      (Arith. mean) obtained during 24 hours were used in the analysis. RESULTS: The
      following results were obtained: Me = 1.57, Arith. mean = 1.97 in control group,
      Me = 2.57, Arith. mean = 3.12 in patients with acute HBV, Me = 1.47, Arith. mean
      = 1.77 in patients with chronic HBV. On the basis of the statistical analysis, no
      statistically significant differences in gastric secretion determined with the
      help of 24-hour pH-metry were found between the analysed groups. CONCLUSION:
      Patients with acute and chronic HBV do not display statistically significant
      differences in gastric secretion determined with the help of 24-hour pH-metry.

PMID- 12211734
TI  - Range of serum bile acid concentrations in neonates, infants, older children, and
      in adults.
AB  - BACKGROUND: Serum total bile acids (tBA) determination is a non-invasive, simple
      and very sensitive diagnostic test in evaluation of liver disorders. However, its
      usefulness is limited by lack of the data on normal value range of serum tBA
      concentrations in children, especially neonates and infants. The aim of the study
      was evaluation of serum tBA concentrations according to the age and gender of
      children, and their comparison with the values found in adults. MATERIAL AND
      METHODS: Serum tBA concentration measurements were performed using enzymatic
      colorimetric test Enzabile (Nycomed Pharma, N) in blood samples collected 3 hours
      after last meal in newborns and infants, and fasting in children over 1 year of
      age. The studied children were healthy, without any abnormalities on physical
      examination. In adults, the measurements were performed in fasting patients with
      inguinal hernia without any other concomitant diseases scheduled for elective
      surgery. Two hundred seventy eight children (145 females and 133 males) of ages
      ranging from the 1st day of life to 16 years, and 63 adults (39 males and 24
      females) were investigated. RESULTS: Serum tBA concentrations in newborns (mean
      (SD: 19.6 +/- 5.2 mumol/l) were significantly higher than the values found in
      adults (5.1 +/- 2.9 mumol/l). Serum tBA concentrations increased gradually after
      delivery, with peak values occurring at the age of 1 month (22.2 +/- 5.1
      mumol/l), which then gradually declined to nearly adult levels. No gender-related
      differences were observed in serum tBA concentrations in children. CONCLUSIONS:
      It is mandatory to refer to the age of the patient, interpreting values of serum
      tBA concentration in children.

PMID- 12211735
TI  - Correlation between liver damage and degree of gastric mucose colonization by
      Helicobacter pylori in subjects with parenchymatous liver damage.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) is an important factor responsible
      for chronic inflammatory conditions of the gastric mucosa. It has been
      demonstrated in numerous animal studies that some Helicobacter species may cause
      parenchymatous liver damage. The aim of the study was to investigate whether
      there is any correlation between the incidence of parenchymatous liver damage,
      and the incidence and degree of colonization of the gastric mucosa by H. pylori.
      MATERIAL AND METHODS: The study was carried out in the group of 30 patients (14
      females, 16 males) whose mean age was 37 years, hospitalized because of
      parenchymatous liver damage without clinical symptoms of cirrhosis. All the
      patients had gastroscopy and urease tests performed, and mucosal biopsies were
      taken for immunomorphological investigations. The patients were divided into
      groups, group I comprising those with positive, and group II with negative urease
      test results. RESULTS: Positive urease tests were obtained in 26/30 patients
      (group I), 18/26 of whom demonstrated macroscopic changes of the gastric mucosa
      visible in gastroscopy. Group II with negative urease test results comprised 4/30
      patients, 2/4 of whom had detectable changes in the gastric mucosa. The presence
      of H. pylori antigens was demonstrated by gastric mucosa immunomorphology in all
      30 patients. The degree of invasion of H. pylori was visualized by
      immunofluorescence, which allowed to differentiate deep mucosal invasion of H.
      pylori (bacterial antigens present in lymph follicles and at the base of
      muciferous glands) observed in group I in 14/26 and in group II in 1/4 cases and
      superficial invasion (epithelium and mucosal surface) observed in group I in
      12/26, in group II in 3/4. CONCLUSIONS: The obtained results may suggest more
      frequent H. pylori infections in subjects with parenchymatous liver damage than
      in the population without liver damage. Immunofluorescence seems to be a highly
      sensitive method allowing for detection of even small degrees of gastric mucosa
      colonization by H. pylori.

PMID- 12211736
TI  - HELLP syndrome in primigravida related to disturbances in fatty acid oxidation in
      foetus.

PMID- 12211737
TI  - Effect of high fiber vegetable-fruit diet on the activity of liver damage and
      serum iron level in porphyria cutanea tarda (PCT).
AB  - BACKGROUND: During the treatment of coronary heart disease with a vegetable-fruit
      diet, we have observed the positive effect of the treatment on PCT patients.
      Therefore, we have now examined the short-term results of the diet on the
      selected PCT activity parameters. The study was approved by our Review Board.
      MATERIAL AND METHODS: A group of 13 male PCT patients (mean age 52 years) was
      evaluated. We assessed the body mass index (BMI), serum iron level, activity of
      transaminases (ALT, AST), severity of skin symptoms, and urinary prophyrins
      excretions, before and after a three-week period of vegetable-fruit diet. The
      diet was of natural vegetable/fruit products, and its daily caloric content was
      ca. 500 kcal/day. RESULTS: The mean BMI before and after the diet period were
      26.8 +/- 4.7 vs. 25.8 +/- 4.3 (p = 0.001), the serum activities of ALT 122.0 +/-
      60.7 U/l vs. 75.6 +/- 31.8 U/l, and of AST 91.8 +/- 56.0 U/l vs. 55.2 +/- 14.2
      U/l (p = 0.001), respectively. The mean serum iron levels were 188.6 +/- 75.7
      mg/dl vs. 140.2 +/- 56.4 mg/dl, serum ferritin concentrations 574 +/- 351 vs. 499
      +/- 340 ng/ml (p = 0.04), respectively. Severity of skin lesions and urinary
      coproporphyrins excretion were significantly diminished during the diet; urinary
      uroporphyrins excretion was also lowered, but not to a statistically significant
      level. CONCLUSION: In our group of PCT patients, we noticed the beneficial effect
      of the vegetable-fruit diet on selected disease parameters. The diet may be
      useful in the treatment of PCT and diseases associated with PCT.

PMID- 12211738
TI  - Results of rubber band ligation of esophageal varices.
AB  - BACKGROUND: The aim of the paper is to analyze the results of endoscopic rubber
      band ligation of esophageal varices performed between 1 January 1998 and 1
      November 2000 at the Department of GI Surgery of 4th Military University
      Hospital. MATERIAL AND METHODS: Cases of 50 patients with massive upper GI
      variceal bleeding present on admission or with the history of such a bleeding
      were reviewed. A total of 85 endoscopic procedures of rubber band ligation were
      performed. In 9 (18%) cases ligation was performed due to massive variceal
      bleeding, in 1 case the complementary obliteration of stomach fundus varices with
      Aethoxysclerol was performed. In 10 (20%) cases in grade C of Child-Pough scale
      of liver failure, 3 endoscopic procedures were performed, in 15 (30%) in grade B-
      2 procedures, in the remaining 25 (50%) cases, also in grade B--1 procedure was
      performed. Procedures were conducted with Wilson-Cook Multi-Band Ligator SAEED
      SixShooter. RESULTS: In all cases with non-bleeding esophageal varices the
      overall good result of treatment was achieved, with collapsing of variceal
      columns. In 8 (88.8%) of 9 cases treated due to variceal bleeding, good
      hemostasis was achieved and no reintervention was necessary. In 1 case of massive
      variceal bleeding endoscopic treatment failed and patient eventually died. In 25
      (50%) cases the complementary (1 or 2) rubber band ligations were performed.
      Follow-up period has ranged from 1 to 34 months. No cases of severe complications
      after the procedure were noted. In early period after the procedure 43 (86%)
      patients complained of transient, mild retrosternal pain and mild to moderate
      dysphagia. CONCLUSIONS: Endoscopic rubber band ligation is a safe and effective
      treatment for esophageal varices both in cases of variceal bleeding and as
      elective procedure.

PMID- 12211739
TI  - Liver cystadenocarcinoma--case report.
AB  - A 69-year-old woman was admitted to our Department with the diagnosis of liver
      cyst. She had previously undergone liver cyst fenestration 10 years before. After
      abdominal spiral CT, the patient was qualified for laparotomy. A cystic formation
      was localized in the central part of the liver, in the 4th segment and was found
      to compress the hilar bile ducts. A 4.5 bisegmentectomy was performed. During the
      postoperative course, a biliary fistula was observed, which resolved
      spontaneously. The treatment was also complicated by myocardial infarction. The
      patient was discharged in good condition 30 days postoperatively. The
      pathological diagnosis revealed cystadenocarcinoma.

PMID- 12211740
TI  - Risk factors for morbidity following liver surgery.
AB  - The aim of this study is to define risk factors for severe complications
      following anatomical liver resections. The study material consists of the first
      50 patients (26 women, 24 men, at mean age 50.6 years) treated at 3rd Department
      of Surgery 2nd Faculty of Medicine, Medical University in Warsaw. The indications
      for resection included benign neoplasm in 19 cases and malignancy in 31 cases.
      All the patients underwent anatomical liver resection in accordance with
      Couinaund's segmental division. In order to define prognostic factors for severe
      postoperative complications, a multi-factor statistical analysis was conducted.
      The following parameters were analysed: patient's age, the levels of bilirubin,
      total protein, albumin, prothrombin time, kaolin-kephalin time, range of
      resection and blood loss during operation. Eleven patients (22%) died in
      postoperative period. In 8 cases the death was caused by liver failure.
      Statistical analysis showed that blood loss, albumin level on fifth postoperative
      day and kaolin-kephalin time before and after surgery are independent risk
      factors predisposing to the development of complications.

PMID- 12211741
TI  - Liver regeneration after anatomical resections.
AB  - BACKGROUND: The authors present the results of investigation of liver
      regeneration after partial parenchyma resection. MATERIAL AND METHODS: 20
      patients (16 females, 4 male) aged 31-67 years were operated on because of
      metastatic colon cancer (7 cases), cavernous hemangioma (6 cases), hepatocellular
      carcinoma (1), alveococcosis (2), metastases of malignant melanoma (1), gall
      bladder carcinoma (1), FNH (1) and mucous cystadenocarcinoma (1). The resection
      according to anatomical segments by Couinaud were performed. Spiral CTs including
      liver volumetry were taken before and 30 days after the operation. on the 7-th
      day after the surgery, liver biopsy was performed and the material was examined
      under light and electron microscope. RESULTS: There was no postoperative
      mortality. We observed transient elevation of transaminases, bilirubin levels and
      decrease of albumin level. Control spiral CT revealed increased liver volume in
      15 cases (75 percent). In 16 cases (80 percent), electron microscopy
      investigations showed regeneration of the liver (mitotic figures). CONCLUSIONS:
      Our material shows that hyperplasia as well as blood vessel and bile duct
      neogenesis play a very important role in liver regeneration process.

PMID- 12211742
TI  - Hepatic artery thrombosis in patients after liver transplantations.

PMID- 12211743
TI  - Intrahepatic portosystemic shunt in treatment of complications of portal
      hypertension.
AB  - BACKGROUND: The aim of the paper is to present the role of transjugular
      intrahepatic portosystemic shunt (TIPS) in the treatment of portal hypertension
      complications such as variceal bleeding and persistent ascites. MATERIAL AND
      METHODS: Between June 1992 and December 2000, 56 patients with portal
      hypertension developed in the course of hepatic cirrhosis were qualified for
      TIPS. The indications for TIPS included esophageal variceal bleeding, recurrent
      despite endoscopic treatment (N-40), active esophageal variceal hemorrhages in
      which traditional methods used to stop the bleeding proved ineffective (N-8) and
      ascites failing to respond to high doses of diuretic agents (N-8). The studied
      group consisted of 30 females and 26 male patients aged from 17 to 68 (mean age
      52 yrs). According to Child-Pugh surgical risk classification, 26 patients
      belonged to group B, and 30 to group C. RESULTS: In 50 patients (83.5%) an
      intrahepatic shunt was formed and the stent(s) implanted. In 42 cases (75%), long
      lasting patency of the shunt was obtained and esophageal variceal bleeding was
      stopped. Active esophageal variceal hemorrhages were stopped in all the cases.
      The remission of massive ascites and hepatorenal syndrome was obtained in 7 out
      of 8 patients. CONCLUSIONS: TIPS is a non-surgical method relieving portal
      hypertension in patients with variceal hemorrhages recurrent despite endoscopic
      treatment. Very good results were also obtained in the cases with active variceal
      hemorrhages. TIPS has proved to be an effective method of treatment in the
      patients with massive ascites and hepatorenal syndrome.

PMID- 12211744
TI  - Lymphocyte subsets in peripheral blood and bronchoalveolar lavage in patients
      with primary biliary cirrhosis.
AB  - BACKGROUND: The objective of this study was to examine the hypothesis that total
      blood and bronchoalveolar lavage (BAL) lymphocytes and their subsets in patients
      with primary biliary cirrhosis (PBC) with coexistent alveolitis are different
      from those in patients with PBC alone. Total blood and BAL lymphocytes and their
      subsets were evaluated in both types of patients and compared with a control
      group of normal healthy subjects. MATERIAL AND METHODS: 17 patients with well
      documented PBC were divided into two groups: Group A--patients with coexisting
      alveolitis and Group B--patients with no alveolitis. Diagnosis was based on
      bronchoalveolar lavage. The control group consisted of healthy subjects. The
      lymphocyte subsets, including CD3, CD4, CD8, CD20 and CD56 were identified in
      blood and BAL cytospin smears using specific monoclonal antibodies. RESULTS: The
      percentage of CD3 and CD8 lymphocytes in BAL was significantly lower in a Group
      A, whereas the percentage of NK was significantly increased in group B as
      compared with the reference group. The percentage of blood CD4 lymphocytes in
      both subgroups of the PBC patients was significantly decreased as compared with
      the controls. The percentage of NK in both groups was significantly increased as
      compared with the controls. CONCLUSIONS: The relationship between the blood and
      BAL lymphocyte subsets in both studies groups were similar. Therefore, we suggest
      that PBC is a systemic disease in which lymphocytic infiltrations are not limited
      to the liver but may also involve lungs and probably other organs.

PMID- 12211745
TI  - Anticholestatic activity of flavonoids from artichoke (Cynara scolymus L.) and of
      their metabolites.
AB  - It is well known that water-soluble extracts of artichoke (Cynara scolymus L.)
      leaves exert choleresis. When studying this effect in vitro using primary
      cultured rat hepatocytes and cholephilic fluorescent compounds, it was noticed
      that the artichoke leaf extracts not only stimulated biliary secretion, but that
      they also reestablished it when secretion was inhibited by addition of
      taurolithocholate to the culture medium. Furthermore, taurolithocholate-induced
      bizarre bile canalicular membrane distortions detectable by electron microscopy
      could be prevented by artichoke leaf extracts in a dose-dependent manner when
      added simultaneously with the bile acid. These effects were exerted by the
      flavonol luteolin and, to a lesser extent, by luteolin-7-O-glucoside, while
      chlorogenic acid and 1.5-dicaffeoyl quinic acid were almost ineffective.
      Surprisingly, metabolites produced by the cultured hepatocytes were able to
      stimulate biliary secretion substantially as well as prevent canalicular membrane
      deformation. These results demonstrate that artichoke leaf extracts exert a
      potent anticholestatic action at least in the case of taurolithocholate-induced
      cholestasis. Flavonoids and their metabolites may contribute significantly to
      this effect.

PMID- 12211746
TI  - New therapeutic options of carcinoid syndrome metastatic to the liver.
AB  - Carcinoid syndrome is a relatively rare disease, generally associated with poor
      prognosis. Conventional diagnostic and therapeutic methods often prove inadequate
      and ineffective. New therapeutic options have recently been provided by
      Radiolabeled long-acting somatostatin analogs (Octreotide), alpha interferon, 131
      MIBG and non-pharmacological methods--embolization of the hepatic artery, gene
      therapy, and combined therapies.

PMID- 12211747
TI  - Correlation between the haemodynamics of portal collateral circulation and the
      incidence of esophageal bleeding in patients with portal vein thrombosis--a
      preliminary report.
AB  - The aim of this study was to determine a correlation between the haemodynamics of
      portal collateral circulation (PCC) and the incidence of bleeding episodes. The
      prospective analysis included 17 patients with portal hypertension resulting from
      prehepatic block but without history of oesophageal bleeding. Every two months
      the changes in PCC and incidence of oesophageal bleeding were evaluated. The
      follow-up ranged from 3 to 12 months. The statistical correlation between the
      portal haemodynamic disorders and the tendency to bleed was investigated.
      Variceal bleeding occurred in 6 patients during the time of observation, mostly
      in patients with development of hepatofugal PCC. Authors suggest that the
      development of hepatofugal PCC is the main factor of variceal bleeding in
      patients with portal vein thrombosis (PVT).

PMID- 12211748
TI  - Support of diagnosis of liver disorders based on a causal Bayesian network model.
AB  - We describe our work on HEPAR II, a probabilistic causal model for diagnosis of
      liver disorders. The model, a Bayesian network capturing the causal interactions
      among various risk factors, diseases, symptoms, and test results, is based on
      expert knowledge combined with clinical data captured in medical records. The
      main applications of HEPAR II are assistance is diagnosis and training of
      beginning diagnosticians. We outline the principles of the applied approach,
      present a brief description of the model, and report its diagnostic performance.

PMID- 12211749
TI  - Harvesting II and III hepatic segments from live related donors.

PMID- 12211750
TI  - Diagnosis of chronic hepatitis.
AB  - In this brief review the basic information concerning diagnosis of chronic
      hepatitis is presented. The evaluation of patient with chronic hepatitis must
      consider a number of possible etiologies. In some chronic hepatitis cases hepatic
      injury may be due to more than one agent. Because the clinical signs of chronic
      hepatitis are not characteristic or the course of disease may be asymptomatic
      special attention should be dedicated to biochemical, immunological and
      virological tests. The most sensitive and specific tests and techniques should be
      used in differential diagnosis. The knowledge about extrahepatic manifestations
      of liver diseases, mainly due to immunological disorders, is also very important.
      However, the role of liver biopsy in chronic hepatitis cases is essential to
      confirm the diagnosis and indicate the possible etiology.

PMID- 12211751
TI  - Management of iatrogenic lesions of the biliary tract.
AB  - A wide spectrum of iatrogenic biliary complications is encountered. Most are the
      results of preventable trauma or technical mishaps during cholecystectomy. There
      is no doubt that the incidence of iatrogenic lesions of the bile tract increased
      since the introduction of laparoscopic cholecystectomy. These include bile
      leakage, biliary tree obstruction, postsurgical strictures and various types of
      biliary fistulas. The purpose of this article is to review the clinical features
      of these iatrogenic lesions with emphasis of their interventional and surgical
      management.

PMID- 12211752
TI  - Surgical treatment of hilar cholangiocarcinoma (Klatskin tumor)--analysis of the
      curative strategies.

PMID- 12211753
TI  - Acute liver failure due to Wilson's disease.

PMID- 12211754
TI  - Interventional radiological and endoscopical techniques in biliary tract
      obstruction.
AB  - For years biliary tree was explored and treated exclusively by open surgery.
      These method, as a treatment of choice of obstructive jaundice, supported by
      intraoperative cholangiography or cholangioscopy is widely acceptable up to now
      despite questions of adequacy, technical problems in cancer patients, time needed
      either for procedure and postoperative care of patients. More than 50 years ago,
      first diagnostic (followed in a short time by therapeutical modalities)
      transhepatic opacification of bile ducts was reported. During next 20 years, to
      the era of endoscopy, such approach remained the most accurate diagnostic and
      interventional tool in this area. In 1968 first endoscopic opacification of bile
      duct was reported and 6 years after, first endoscopic sphincterotomy in patients
      with common bile duct stones was done in Germany and in Japan. In the late 70s
      first endoscopical nasobiliary drainage and endoscopical insertion of biliary
      stents was announced. Today noninvasive methods, like Magnetic Resonance
      Cholangiopancreatography, 3 D Ultrasound Scanning or Computed Tomography,
      replaced both techniques mentioned above in diagnostic field. However,
      therapeutical procedures and histological confirmation of the disease origin
      remains in hands of interventional radiologists and endoscopists. This brief
      description presents present and future techniques of less invasive therapeutical
      approach to the biliary tree.

PMID- 12211755
TI  - Gene therapy of primary and metastatic liver tumors.

PMID- 12211756
TI  - Extracorporeal support of the failing liver.

PMID- 12211757
TI  - Tumors of the bile ducts--pathological aspects.

PMID- 12211758
TI  - Toxicology. What's your poison?

PMID- 12211759
TI  - Should nurses new to the NHS be tested for HIV?

PMID- 12211760
TI  - Should Best get a shot at extra time?

PMID- 12211761
TI  - Our midwives really do deliver the goods.

PMID- 12211762
TI  - Cutting edge nursing.

PMID- 12211764
TI  - The media should get its facts right when writing NHS horror stories.

PMID- 12211763
TI  - Global resistance.

PMID- 12211765
TI  - Cancer care. Part 2. How cancer service users can influence research and
      practice.
AB  - There is increasing cooperation between NHS service providers and patients, who
      provide feedback on the care they receive and make suggestions for research and
      changes in practice. This article discusses why such links are necessary and
      describes the cancer research open day organised by a cancer network as one
      example of a forum for such exchanges of information to take place. The authors
      believe this example of collaborative interaction between patients and health
      professionals can be adapted and used by nurses working in a variety of health
      care settings.

PMID- 12211766
TI  - Focusing nursing care on the older person.
AB  - The second article in our two-part series on gerontological nursing features two
      case studies that flag up examples of good practice in two clinical areas. The
      first describes a nurse manager's four-year catering services review, which
      resulted in a new approach to nutrition and benefited older patients in a rural
      hospital. The second describes how a charge nurse and staff on a long-stay
      elderly care ward used a psychosocial approach to end ward routines and introduce
      individualised care. The results, although not yet formally assessed, are
      encouraging and staff hope their experience and collaboration with the University
      of Paisley will help other nurses working in the specialty.

PMID- 12211767
TI  - Improving services by listening to patients.
AB  - When an elderly care unit took part in a national survey of patients' views, the
      results prompted staff to try to improve the service they offered. Changes were
      made on the basis of the survey, including improved patient information, changes
      in visiting hours and the provision of activities for patients. Further surveys
      have shown increased patient satisfaction, while staff morale has improved and
      sickness absence has decreased.

PMID- 12211768
TI  - Developing the nurse practitioner's role in minor surgery.
AB  - The role of a minor surgery nurse practitioner has been developed to benefit
      patients, the hospital trust and the nurse herself. An experienced theatre nurse
      was given intensive training by the surgical team, enabling her to provide a one
      stop clinic for minor surgical procedures. Using local anaesthesia, the nurse
      removes common lesions such as moles, cysts and lipomas. Patients can bypass the
      wait for an outpatient appointment and subsequent day surgery. The success of the
      project has led to the introduction of a course in minor surgical skills for
      nurse practitioners in a range of specialties including dermatology, accident and
      emergency and primary care. The aim is to develop joint training for junior
      doctors and nursing staff.

PMID- 12211769
TI  - Cardiopulmonary resuscitation. Administration of medicines.

PMID- 12211770
TI  - Day in the life.

PMID- 12211771
TI  - The UNOS renal transplant registry.
AB  - The shortage of cadaver kidneys relative to increasing demand for transplantation
      has lead to a remarkable rise in transplantation from living donors. Based upon
      data reported to UNOS, the number of living donor kidneys transplanted in 2000
      (5,106) nearly equaled the number of cadaver kidneys from preferred donors aged 6
      50. HLA-mismatched siblings, offspring, spouses and other genetically unrelated
      donors accounted for nearly 80% of increased living donor transplantation during
      1994-2000. Despite the increased use of poorly HLA-matched living donor kidneys,
      the actuarial 10-year graft survival rates for transplants between 1988-2000 were
      clustered between 53-57% for HLA-mismatched living donor grafts, except for
      offspring-to-parent transplants (49%) when the recipients were generally older.
      The 10-year survival rate for 96,053 cadaver grafts was 38% during the same
      period. The 5-year graft survival rates for more recent (1996-2000) cadaver donor
      transplants were 66%, 62% and 56% for recipients of first, second and multiple
      grafts, respectively (p < 0.001). The comparable results among recipients of
      living donor kidneys were 67%, 66% and 59% (p = ns). The 5-year graft survival
      rates for HLA-matched first grafts were 7% higher than those for HLA-mismatched
      transplants when the kidney was from a living or cadaver donor. HLA-identical
      sibling transplants provided the best long-term graft survival (85% at 5 years
      and a 32 year half-life). Even with improved crossmatch tests and stronger
      immunosuppression, sensitization was associated with 8% lower graft survival at 5
      years and with a higher rate of late graft loss among first cadaver kidney
      recipients. Sensitization also was associated with an increase in delayed graft
      function from 22% of unsensitized first transplant recipients to as much as 36%
      among multiply retransplanted patients. Recipient race was a key factor in long
      term graft survival of both living and cadaver donor kidneys. The rate of late
      graft loss was double among blacks compared with recipients with other racial
      origins whether the kidney was from a living or cadaver donor. Black recipients
      accounted for 29% of first cadaver transplants during 1996-2000, but only 14% of
      living donor grafts. Thus an important component of long-term differences in
      graft survival comparing living and cadaver donor transplants is the disparate
      racial demographics. Both the recipient and donor populations are aging. The
      proportion of cadaver kidney recipients over age 50 increased from 26% to 45% and
      the proportion of living donor kidney recipients over age 50 rose from 10% to 35%
      between 1988 and 2000. The aging population affects the transplant outcome as 65%
      of graft losses among young recipients (ages 10-15) were attributed to acute or
      chronic rejection compared with only 25% of grafts lost among patients over age
      60. More than half of graft losses among older recipients were due to death with
      a functioning graft. Kidneys from donors over age 60 comprised 9% of first
      cadaver transplants and yielded a 50% 5-year graft survival rate compared with
      70% when the donor was aged 19-45. Kidneys from donors over age 60 accounted for
      only 3% of first living donor transplants and their 84% 5-year graft survival
      rate was comparable to that for younger donor kidneys. Despite declining
      immunological graft losses with advancing recipient age, the effect of HLA
      matching was similar among recipients of first cadaver transplants aged 50 or
      under and those over age 50. Completely HLA-mismatched grafts had a 10% lower 5
      year graft survival rate than HLA-matched grafts when the recipient was over 50
      compared with a 14% lower survival rate in younger recipients. The graft half
      lives were shorter by 5-7 years for HLA-mismatched kidneys transplanted to older
      or younger recipients, respectively.

PMID- 12211772
TI  - The dual kidney transplant registry.
AB  - There has been a steady increase in the utilization of aged donor kidneys for
      dual transplantation during the past several years. As the follow-up of these
      dual kidney recipients accrues, it is clear that the long-term graft survival
      rate approaches that seen in recipients of single kidneys transplanted from
      younger donors. Because the kidneys used for dual kidney transplants would have
      otherwise been discarded, it is imperative to recognize that kidneys from cadaver
      donors that fall outside the normal acceptance criteria are a valuable resource
      and can provide excellent long-term function when properly placed. Reducing cold
      storage time may be the single most important aspect to insuring long-term graft
      survival in recipients of aged dual kidney transplants.

PMID- 12211773
TI  - Laparoscopic live donor nephrectomy at the University of California San
      Francisco.
AB  - Laparoscopic donor nephrectomy is quickly becoming the preferred technique for
      kidney retrieval, since it removes many of the disincentives of kidney donation.
      Our experience at UCSF has confirmed that the procedure is safe, with excellent
      donor recovery. The transplanted kidney appears to function as well as any kidney
      retrieved using an open technique, at least in the short-term. Development of a
      successful laparoscopic donor program is best done initially with a team
      approach, utilizing the skills of an advanced laparoscopic surgeon, and with
      careful patient selection. With time, the technique can be done well by properly
      trained transplant surgeons with basic laparoscopic skills, with or without a
      hand-assist technique. As experience grows, this procedure can be applied to
      virtually every potential donor, and hopefully will improve live kidney donation
      rates.

PMID- 12211774
TI  - The kidney transplant program at the Massachusetts general hospital.
AB  - Between February 1963 and December 2000, 1,627 kidney transplants were performed
      at the Massachusetts General Hospital. The majority (62%) were from cadaveric
      donors, although in recent years (1996-2000) 52% have been allografts from living
      donors, with an increase in living unrelated donors. The introduction of CsA and
      OKT3 in 1984 was associated with a significant improvement in actuarial renal
      allograft survival, although a persistent late attrition of allografts continues
      beyond the first year after transplantation. As reported in other centers,
      current actuarial survival for living unrelated allografts is superior to that of
      cadaveric allografts, and is quite similar to that observed in recipients of non
      HLA identical living-related transplants. Our preliminary laparoscopic donor
      nephrectomy experience is encouraging as excellent allograft survival and
      function has been observed, with minimal morbidity associated with the procedure
      and a low rate of conversion to open nephrectomy. Recent changes in
      immunosuppressive protocols have resulted in lower early acute rejection rates,
      however the incidence of delayed graft function remains unchanged in cadaveric
      renal transplantation. The role of humoral immunity in allograft rejection has
      been progressively clarified and new approaches to control donor specific
      alloantibody production have been shown to be effective. Current clinical studies
      are ongoing to determine the optimal type and dose of calcineurin inhibitors
      beyond the first year after transplantation and to study whether avoidance of
      steroids is safe and feasible. Finally, an innovative tolerance induction
      protocol using the mixed chimerism approach has been successfully accomplished in
      selected patients with end-stage renal disease secondary to multiple myeloma.
      These encouraging observations emphasize that major changes from current
      immunosuppressive regimens are likely to occur over the next few years as more
      approaches to tolerance induction are explored clinically.

PMID- 12211775
TI  - The Barnes-Jewish Hospital/Washington University Renal Transplant Program:
      comparison of two eras 1991-1994 and 1995-2000.
AB  - The first cadaveric transplant at Barnes-Jewish Hospital/Washington University
      was performed in 1963, the first living related transplant in 1965, and the first
      living unrelated transplant in 1983. Changes in the renal transplant program
      initiated in 1993 and 1994 resulted in many improvements over the past decade.
      Our comparison of 2 modern eras of transplant, 1991-1994 and 1995-2000, showed
      the following: 1. No significant differences in patient and donor
      characteristics. 2. Trends toward greater use of living donors (p = 0.07), older
      cadaveric donors (p = 0.084) and particularly cadaveric donors > 55 years of age
      (p = 0.09). 3. Decreasing mean CIT: 19.2 hours vs. 14.2 hours (p < 0.001). 4.
      Decreasing use of donors with CIT > 24 hours: 22% to 3%, (p < 0.001). 5.
      Decreased rate of DGF: 13% vs. 8% (p = 0.044). 6. Decreased rate of symptomatic
      CMV: 35% vs. 14% (p < 0.001). 7. Decreased rate of PTLD: 3.5% vs. 0.5% (p =
      0.004). 8. Decreased one-year rate of acute rejection: 41% vs. 15% (p < 0.001).
      9. Current one-year rate of acute rejection < 8%. 10. Decreased length of initial
      hospital stay: 12.7 days to 8.0 days (p < 0.001). 11. Decreased length of
      hospital in the first year after transplant: 10.6 days vs. 6.4 days (p < 0.001).
      12. There were no improvements in patient and graft survival at one and 3 years.
      a. one-year patient survival rates: 95% vs. 96%. b. 3-year patient survival
      rates: 90% vs. 90%. c. one-year death-censored graft survival rates: 91% vs. 94%.
      d. 3-year death-censored graft survival rates: 87% vs. 88%.

PMID- 12211776
TI  - Cadaveric renal transplantation in African-Americans in South Carolina.
AB  - The renal transplant program at the MUSC was established in 1968 and is the only
      transplant center in South Carolina. It serves a large population of African
      American patients who constitute nearly two-thirds of the waiting list and more
      than half of all renal transplants. Between 1968-2000, 969 transplants were
      performed in 906 AA patients. Most received organs from cadaveric donors, while
      only 99 (10%) of AA patients received living donor transplants. The acceptance of
      living unrelated donors and the use of laparoscopic nephrectomy have had a
      negligible impact on living donations in this racial group. Primary disease had
      little effect on outcome except in diabetics whose mortality was higher. The one
      year graft survival rates improved dramatically with the aggressive use of CsA
      without the use of antibody induction. The overall one- and 5-year graft survival
      rates improved from 53% and 32%, respectively, in the 1978-1983 era to 87% and
      59%, respectively, in the 1993-2001 era. At MUSC, the emphasis has been on
      reducing mortality due to sepsis by limiting the number of rejections treated
      particularly in recipients of cadaveric organs. While this has resulted in
      reduced overall early mortality, it has not adversely affected graft survival.
      Our experience suggests that while short-term graft survival has improved
      significantly over the years for AA patients, the long-term outcome still remains
      relatively unchanged.

PMID- 12211777
TI  - Living-unrelated renal transplantation at the University of Wisconsin.
AB  - Since 1984, we have performed 243 living-unrelated renal transplants at the
      University of Wisconsin. Rejection occurred in 47% of the patients. Graft loss
      occurred in 59 patients and 39 patients died. Graft survival in LURD transplants
      at 10 years is 54% and 43% at 15 years. Patient survival is 68% at 10 years and
      54% at 15 years. These long-term results demonstrate that LURD is equivalent to
      haploidentical renal transplantation and superior to cadaveric transplantation.
      Husband-to-wife donation demonstrated improved graft survival when compared with
      wife-to-husband and nonspousal donation. Living-unrelated renal transplantation
      has been utilized successfully at the University of Wisconsin and may help to
      alleviate the donor shortage.

PMID- 12211778
TI  - Early and long-term results using older kidneys from cadaver or living donors.
AB  - The persisting shortage of organs for transplantation justifies the use of all
      possible donors. We compared results for 110 patients, who received solitary
      kidneys from cadaver donors over age 60 years (OCD) with those for 976 patients,
      who were transplanted with kidneys from 11-49-year-old cadaver donors, whom we
      defined as "ideal" age. Although the 4% incidence of primary nonfunction and the
      24% rate of delayed graft function were significantly higher (p < 0.001) in the
      OCD group compared with the ideal group (0.8% and 8.0%, respectively), OCD
      kidneys can offer good results when low-risk recipients are carefully selected
      and the cold ischemia time is sharply reduced. Moreover, graft survival rates for
      14 OCD grafts, implanted in patients under age 45 were 93% at one, 3 and 10 years
      compared with 79%, 74% and 42% at the same time points for 96 OCD recipients over
      age 45. The rate of delayed graft function was higher among 19 OCD grafts
      preserved for more than 20 hours, and these grafts yielded significantly lower
      survival rates than 91 OCD grafts preserved for less than 20 hours; with rates of
      67%, 58% and 44% and 85%, 81% and 51%, respectively, after one, 3 and 10 years.
      Thirty-five kidneys from living donors over age 60 had comparable overall graft
      survival rates to living donor kidneys from donors under age 60 (92%, 92% and 92%
      vs. 92%, 88% and 80% at one, 3 and 10 years, respectively). An original point
      scoring system, based only on macroscopic evaluation of the graft, avoids the
      need for a biopsy and does not prolong cold ischemia time. Microvascular bench
      reconstructions of the renal artery, damaged by atherosclerosis, expand the
      possibility for safe transplantation of older kidneys without performing a double
      renal transplant.

PMID- 12211780
TI  - Liver transplantation at Dumont-UCLA Transplant Center: an experience with over
      3,000 cases.
AB  - Liver transplantation has seen extraordinary advances over the past 2 decades and
      now represents the only life-saving therapy for many patients with decompensated
      liver disease, regardless of etiology. As the indications for transplantation
      expand, the patient waiting list continues to grow, while the number of available
      donors each year remains relatively constant. As a result, there is a marked
      shortage of donor organs, prolonging the waiting time and thereby increasing the
      mortality of patients while waiting for OLT. At UCLA, we are actively pursuing
      novel approaches to increase retrieval of transplant organs. The use of in-vivo
      split-liver transplantation represents an effective technique to safely expand
      the number of organs and also provides a size-matched organ for pediatric
      patients. Living-donor liver transplantation represents a significant surgical
      achievement in an effort to expand the critical shortage of donor organs.
      However, the added risk imposed on a healthy individual by the use of this
      technique raises serious bio-ethical concerns. Although the results of OLT have
      improved substantially, most of the current recipient morbidity and mortality
      results from recurrence of disease, infectious complications, rejection, PNF, and
      technical complications. The development of effective pharmacological agents to
      prevent disease recurrence, as well as improvements in immunosuppression therapy
      will be important issues in the upcoming decade.

PMID- 12211779
TI  - Live-donor renal transplantation at the Urology & Nephrology Center of Mansoura:
      1976-1998.
AB  - Based on more than 1,200 living donor transplants performed at the Urology &
      Nephrology Center at Mansoura University between 1976-1998, we report: 1. The
      overall graft survival rate was 75.8% and 51.9% at 5 and 10 years, respectively,
      with a projected half-life of 10.7 years. 2. Three factors acted as independent
      variables that significantly influenced graft survival: the number of HLA
      mismatches, the number of acute rejection episodes and the presence of
      posttransplant hypertension. a. Grafts with 2 or fewer HLA-A, -B and -DR
      mismatches had a significantly better survival rate. b. The incidence and the
      number of early acute rejection episodes had a significant negative impact on
      graft survival. c. A significant reduction in graft survival was associated with
      hypertension uncontrolled by or newly developed after transplantation. 3.
      Bilharziasis had no impact on the outcome. 4. Despite improvements in tissue
      matching and immunosuppression, an important proportion of grafts is still lost
      following living-donor kidney transplantation. 5. Efforts must be directed to
      identify better regimens, which can provide adequate immunosuppression and
      minimal nephrotoxicity.

PMID- 12211781
TI  - Results of liver transplantation in a Spanish group: a report from the Cordoba
      unit.
AB  - The liver transplantation unit from Cordoba, Spain, performed its first liver
      transplantation in 1989. Since then, 500 liver transplants have been performed in
      our institution up to November 2001. Our one-year recipient and graft survival
      rates are 77% and 76%, respectively. These recipient and graft survival rates are
      lower when compared with other results in the English language literature, and we
      present evidence here that the disparity results from 4 especially problematic
      aspects of our program: 1) the expanded use of donors, 2) the policy of
      allocation and prioritization in our institution, 3) the recurrence of primary
      liver disease and 4) de-novo neoplasms. Liver transplantation with unstable,
      hypernatremic donors or donors with a lengthy hospitalization and grafts with a
      prolonged cold ischemia time leads to diminished graft survival. When several
      marginal criteria accumulate in a donor, the results are even poorer.
      Consequently, the delayed non-function rate is especially high in our series.
      Attention to severe liver preservation injury as a primary mechanism of graft
      losses with marginal donors is given. The impact of the policy of the "sickest
      first" principle in our center with a long waiting list seems to benefit urgent
      but not elective patients. Survival in elective patients is poorer than expected
      considering their clinical condition. The use of the sickest-first or urgency
      principle in our unit has not been efficient or equitable and may partially
      explain the poorer survival of our patients. Finally, the recurrence of primary
      disease and incidence of de-novo tumors after transplantation in our unit are
      similar those reported in English language literature.

PMID- 12211782
TI  - Application of a continuous disease severity score to the OPTN liver waiting
      list.
AB  - In a move to establish measurable, objective criteria for cadaveric liver
      allocation, the United Network for Organ Sharing OPTN will implement the Model
      for End Stage Liver Disease (MELD) system in early 2002 as a replacement for the
      current Child-Turcotte-Pugh (CTP)-based Status 2A, 2B, and 3 categories for
      patients waiting for a cadaver donor liver transplant. The MELD is a continuous
      mortality risk score based on serum creatinine, bilirubin, and INR. Although
      originally developed in patients undergoing the transjugular intrahepatic
      portosystemic shunt (TIPS) procedure, analysis of OPTN data shows that the
      components of MELD (in particular, bilirubin) have a very strong correlation with
      mortality in liver transplant candidates. Univariate analyses showed that
      pretransplant mortality significantly increased when the MELD score was > 1.8. In
      the study cohort, 25% of the patients had a MELD score > 1.8. Multivariate
      analysis showed that the MELD score was an independent predictor of mortality,
      with a 2-unit increase multiplying the risk of mortality by a factor of 5.6. The
      MELD and CTP scores were correlated, but MELD scores varied widely for any given
      CTP score, indicating that some patients could be disadvantaged with the status
      based system. The MELD score was validated in an independent dataset; concordance
      with 3-month mortality was 0.88. We conclude that the MELD score is a good
      indicator of disease severity and that implementation of this system should
      direct more livers to those patients in greatest need of transplantation.

PMID- 12211783
TI  - Living donor liver transplantation in Kyoto, 2001.
AB  - The living-donor liver transplant program at Kyoto University Hospital entered
      its 12th year in 2001. The rapid increase in adult patients that occurred with
      active use of right hemi-liver grafts is now reaching its plateau, limited by OR
      facilities and bed capacity. Graft selection is now being polarized to the left
      lateral section and right hemi-liver, and disease indications are becoming more
      similar to those for Western cadaveric programs, including a program for
      hepatocellular carcinoma. With the active introduction of right hemi-liver
      grafts, donor selection requires more multifactorial attention. Although most
      anatomical variants are managed surgically without significant risk, small-for
      size grafts combined with high-risk patients are often a continuing problem even
      with the use of right hemi-liver grafts. Solutions for small-for-size syndrome
      with or without persistent portal hypertension and massive ascites are urgent
      targets of research. It will take some more time in Japan until the final
      establishment of a mutual compensatory system between cadaveric and living donor
      programs covering medical and socioeconomical aspects is achieved.

PMID- 12211784
TI  - University of Arizona, Cardiac Transplantation: changing patterns in selection
      and outcomes.
AB  - Among 391 patients who received heart transplants at the University of Arizona
      since 1990, the percentage of bridge-to-transplant device patients receiving
      donor hearts has increased from 6.7% to 50%. Survival after transplantation in
      this-bridge-to transplant group and has been consistently 10-15% lower than
      patients who do not require a device. The result has been that our overall
      survival rate is beginning to fall. We have come to 2 major conclusions based on
      these results: First, the current UNOS system ranking candidates as Status 1A,
      1B, and 2 may not identify those who are at higher risk for transplantation. It
      has failed to do so in our program. Rather, by grouping the potential recipients
      into patients with a device, Status 1 nondevice patients, and Status 2 patients,
      we have found a significantly lower survival rate after transplantation in the
      device group. This suggests that the problems shared by device patients such as
      being anticoagulated, having a difficult reoperation at the time of
      transplantation, and having increased inflammation and decreased immunity clearly
      place these patients in a very different risk group than other potential
      recipients. Second, these results lead us to believe that some high-risk device
      patients may not be suitable for transplantation and might be better if treated
      with devices as alternatives to transplantation.

PMID- 12211785
TI  - Center and other factor effects in recipients of living-donor kidney transplants.
AB  - 1. LIVING DONOR KIDNEY TRANSPLANTS: Using 1996-2001 UNOS Registry data, we
      assessed the joint influence of center, 19 pre- and 5 posttransplant factors on
      renal allograft function in 21,830 patients transplanted with living donor
      kidneys. During an initial risk period, 21,033 recipients were projected to keep
      their grafts through one year (an average 96.4% one-year graft survival), and, in
      a second risk period, 17,775 recipients were projected to keep their grafts
      through 5 years (84.5% conditional 5-year graft survival after surviving one year
      posttransplant). 2. CENTER EFFECTS: Following multivariate log-linear analysis,
      57.5% and 26.5% of assignable variation in one- and 5-year living-donor graft
      survival rates were due to the variation across 234 transplant centers. Center
      effect dominated other factors in influencing early outcomes among living kidney
      donor transplants. A program's size was associated with this center effect since
      all large centers (400+ living donor kidneys) had better-than-average one-year
      graft survival rates, whereas smaller centers (< or = 100 grafts) had wide ranges
      in short-term outcomes (87-100%). Center size did not play a role in explaining
      long-term variation, and the extent to which uniformity in care remains the
      responsibility of the original center needs to be investigated. 3. PRETRANSPLANT
      FACTOR EFFECTS: The impact of the 19 pretransplant cofactors on short-term
      outcomes among living donor transplants was clinically small--adjusted one-year
      graft survival rates across all categories exceeded 94%. However, their long-term
      effects were stronger and more typical of cadaveric results. The following 4
      factors, each explaining > 10% of the assignable variation in conditional 5-year
      graft survival, were ranked and independently yielded poor results: 1) kidneys
      from parental donors; 2) grafts in male recipients; 3) teenage/adult recipients
      (> 12 years); and 4) black recipients. Recipient's original disease and body mass
      index, donor's race and age, and HLA matching were highly significant factors,
      but their impact on long-term graft survival was less than those observed
      previously in cadaveric renal transplants. 4. POSTTRANSPLANT FACTOR EFFECTS:
      Short- and long-term outcomes were relatively stable regardless of the
      maintenance drug initiated at hospital discharge. Living donor transplant
      outcomes were similar for Neoral versus Tacrolimus and for MMF versus
      azathioprine. Kidney graft survival among living donor transplants was strongly
      affected by delays in graft function or acute rejection episodes. 5. CONCLUSIONS:
      During the first year posttransplant, the benefits of receiving a living donor
      kidney (versus a cadaver kidney) mitigate negative cofactor risks of graft
      failure. Beyond one-year, recipients of living donor kidneys are subjected to the
      same deleterious effects from cofactors and early posttransplant events that
      impact the long-term graft survival following cadaveric transplantation.

PMID- 12211786
TI  - Maintenance immunosuppression.
AB  - An "intent-to-treat" analysis was developed to examine the administration of
      primary and adjunctive immunosuppressive agents by year of transplant for
      unsensitized, sensitized, multi-organ and living donor transplant recipients by
      centers reporting to the UNOS Registry of Renal Transplant Recipients. Based on
      these analyses, several trends were noted: Tacrolimus became the dominant primary
      agent for multi-organ transplant recipients in 1998, sensitized recipients in
      2000, and unsensitized and living-donor transplant recipients in 2001. MMF became
      the dominant adjunctive agent for all transplants studied in 1996. The
      combination of CsA-MMF was most often administered to unsensitized and living
      donor recipients while Tac-MMF was most often used for multi-organ transplants.
      The trend of decreasing rejection rates from 60% in 1996 to 20% in 2001 was
      similar for each type of transplant studied. Rejection rates were highest with
      the Csa-Aza combination and lowest with the Tac-MMF combination. Combinations
      with the lowest rates of rejection did not necessarily have the highest graft
      outcome. HLA matching decreased rejection rates and improved graft outcome for
      each type of transplant and immunosuppression combination. Graft outcome in HLA
      matched living donor transplants was highest with the less potent CsA-Aza
      combination and lowest with the Tac-MMF combination. Treatment crossover from CsA
      to Tac or Aza to MMF was least frequent among HLA-matched recipients. Crossover
      from MMF to Aza was highest in HLA-matched living donor transplants.

PMID- 12211787
TI  - Crossmatch tests--an analysis of UNOS data from 1991-2000.
AB  - Based on more than 20,000 cadaver donor transplants reported to UNOS between 1991
      2000 with crossmatch results, the following observations were made: 1. One
      hundred sixty-nine transplants performed despite a positive T-cell NIH crossmatch
      (usually with an historical serum sample) were reported to UNOS and had 5%, 6%,
      7%, and 11% lower graft survival at one, 6, 12, and 24 months after
      transplantation compared with negative crossmatch transplants, respectively. 2.
      Transplants with a positive T-cell FCXM (n = 714) yielded 4%, 7%, and 9% lower
      graft survival at one, 6, and 12 months after transplantation compared with
      negative crossmatch transplants, respectively. 3. Transplants with a positive B
      cell crossmatch using NIH, Wash, AHG or flow cytometry XM yielded statistically
      significantly lower (4-6%) graft survival rates compared with B-cell negative
      crossmatch transplants. 4. The differences in graft survival rates comparing
      recipients with a positive versus a negative T-cell crossmatch test (NIH, AHG,
      and FCXM) were significant in univariate analyses; however, only the NIH and FCXM
      showed a significant effect on graft survival after adjustment of other factors
      in a multivariate analysis. 5. Regrafted patients with a positive T- and B-cell
      FCXM experienced a higher incidence of primary nonfunction (12%) compared with
      those who had a negative T- and B-cell FCXM (1%; P < 0.001). Flow cytometric or
      ELISA screening of patient sera in addition to conventional cytotoxic crossmatch
      tests can provide additional information to aid in the final decision of renal
      transplantation.

PMID- 12211788
TI  - Annual trends and triple therapy--1991-2000.
AB  - 1. Although the number of cadaver donor transplants did not increase
      substantially over the past 10 years, unrelated living donor grafts increased
      from 153 in 1991 to 1,661 through 2000. Use of spousal and other unrelated donor
      organs contributed to this increase. There was a modest increase in living
      related donor transplants from 2,328 in 1991 to 3,451 in 2000. 2. Cadaver donor
      graft survival at one year improved from 84% in 1991 to 90% in 2000. In contrast,
      one-year graft survival of living donor transplants only improved from 93% in
      1991 to 95% in 2000. 3. Throughout the 10-year period, approximately 13% of
      transplants were repeat transplants from cadaver donors and roughly 8% were
      regrafts from live donors. 4. Cadaver donor transplants into White recipients
      declined from 68% in 1991 to 60% in 2000. For living donors, the percentage of
      White patients remained constant at about 70%. 5. Graft survival in patients of
      all races was about equal at one year but diverged at 3 years, with Asians having
      the highest and Blacks having the lowest 3-year graft survival rates. 6. Average
      donor age increased from 31.7 in 1991 to 36 in 2000 for cadaveric donor
      transplants and 37.9 in 1991 to 40.4 in 2000 for living donor transplants.
      Cadaveric kidneys from donors older than 50 years of age yielded significantly
      lower 3-year graft survival. 7. Average recipient age for cadaveric donor
      transplants increased from 42.1 in 1991 to 46.8 in 2000. The average recipient
      age for living donor transplants also increased steadily from 33.7 in 1991 to
      42.9 in 2000. There was relatively little effect on graft survival rates for
      advanced age recipients. 8. The percentage of sensitized recipients receiving
      cadaver donor grafts declined from 27% in 1991 to 21% in 2000. Similarly,
      sensitized recipients receiving living donor grafts decreased from 17% in 1991 to
      13% in 2000. Graft survival in patients with more than 50% PRA was lower at 3
      years for patients receiving cadaveric donor grafts. Highly sensitized patients
      receiving living donor grafts had graft survival rates similar to those who were
      not sensitized. 9. Cold ischemia times decreased from an average of 24.2 hours in
      1991 to 18.9 hours in 2000. Improved graft survival rates over those 10 years
      were noted in all groups, and even cold ischemia times more than 36 hours yielded
      3-year graft survivals comparable to those with lower cold ischemia times in
      1998. 10. The need for dialysis has remained constant at about 23% over the last
      10 years for patients receiving kidneys from cadaveric donors. The rate of
      dialysis for patients receiving kidneys from living donors was about 5% for each
      of the 10 years examined. First day anuria increased from 11% in 1991 to 16% in
      2000 for cadaver donor transplants and 3% in 1999 to 5% in 2000 for living donor
      grafts. 11. Cadaveric donor patients requiring dialysis had a 3-year graft
      survival rate of 63% if there was no first day anuria and 56% if they had first
      day anuria. This is in contrast to 80% 3-year graft survival for those with
      immediate diuresis and no need for dialysis. The 3-year graft survival rate for
      those receiving living donor grafts and needing dialysis was 58% if they had
      first day diuresis and 41% if they ware anuric on the first day. Conversely,
      those who had first day function and did not require dialysis had 89% 3-year
      graft survival. 12. Among the patients receiving cadaveric grafts with first day
      diuresis there was a marked reduction in those with rejection, from 21% in 1991
      to 5% in 2000. Similarly, for this type of patient receiving living donor grafts,
      the reduction was 17% in 1991 to 5% in 2000. However, graft survival among these
      patients did not change significantly. The greatest improvement was noted in
      those with first day anuria and no rejection. 13. Patients who did not require
      dialysis, and had rejection prior to discharge decreased markedly from 17% in
      1991 to 3% in 2000 in those receiving cadaveric grafts and 15% in 1991 to 3.9% in
      2000 for those receiving living donors. Graft survival of cadaveric transplants
      in those needing dialysis, with and without rejection, improved the most in the
      10 year period. 14. Hospitalization days for cadaveric transplant recipients were
      reduced from 19 days in 1991 to 10 days in 2000 and 16 days in 1991 to 8 days in
      2000 for recipients of living donor grafts. There was an increase in discharge
      serum creatinine values from 2.3 mg/dl in 1991 to 3.3 mg/dl in 2000 for cadaver
      donor grafts. 15. Double therapy was utilized for about 15% of cadaveric and
      living donors. There was a sharp increase in induction therapy, peaking at 51% in
      1994 and decreasing to 5% by 2000 for cadaveric donor transplants. Induction did
      not improve graft survival for either cadaver or living donor transplant
      recipients. 16. Triple therapy improved graft survival of White and Black
      patients, but did not affect the half-lives in either race. 17. The lower graft
      survival from older donors was not affected by triple therapy for cadaver donor
      transplants. Triple therapy removed the donor age effect for recipients of living
      donor grafts. 18. Triple therapy practically eliminated the effect of
      sensitization for cadaveric donor grafts. Both double and triple therapy
      virtually eliminated the sensitization effect for living donors. 19. Triple
      therapy significantly improved the survival of kidneys with more than 36 hours
      cold ischemia time so that 3-year graft survival was 76% at 3 years compared with
      81% for kidneys stored 1-12 hours. 20. Triple therapy improved the 3-year graft
      survival of kidneys with first day anuria from 50% for double therapy to 69% for
      triple therapy in cadaver donor transplants. For living donor transplants, there
      was a similar improvement from 57% with double therapy to 72% with triple
      therapy. 21. Triple therapy improved the 3-year cadaveric graft survival rate of
      kidneys requiring dialysis from 51% with double therapy to 67% for triple
      therapy. There was a similar improvement for living donors needing dialysis from
      37% to 61% at 3 years.

PMID- 12211790
TI  - Sensitization 2001.
AB  - 1. The rate of transfusion decreased from 64% in 1992 to 36% in 2000. This need
      for transfusions continued despite the introduction of erythropoetin. Females
      were transfused more frequently than males. SLE patients were transfused more
      often than those with other diseases. 2. Transfusions no longer had a beneficial
      effect on the outcome of transplantation, but rather with more transfusions, the
      graft outcome became lower, as might be expected. 3. Rejection of a kidney
      transplant had the strongest effect on sensitization, followed by transfusion and
      then pregnancies. Females were more susceptible to sensitization than males.
      Although non-transfused males should not have been sensitized, as many as 13%
      were reported to have antibodies. As many as 20% of nulliparous females without
      transfusions also were reported to have antibodies. 4. SLE patients were most
      often sensitized among patients with various diseases. Females of all diseases
      were more sensitized than males. 5. Unsensitized regraft patients had a 3% lower
      3-year graft survival than unsensitized first graft patients. Among sensitized
      patients, regraft patients had a 4% lower graft survival than sensitized first
      graft patients. 6. Patients with polycystic kidney disease had the highest 3-year
      graft survival in both the sensitized and non-sensitized patients. Sensitization
      to a PRA level of less than 50% was not detrimental to patients with all the
      various diseases. 7. For cadaver donor regraft patients, HLA-DR mismatch had a
      greater effect than AB mismatch. There was a 10 percentage point lower 3-year
      graft survival in cadaver donor regraft patients mismatched for 2 DR antigens
      than mismatched for 0 DR antigens. 8. For living donor transplants, regrafts from
      0 AB or 0 DR mismatched transplants had the same graft survival as first
      transplants.

PMID- 12211791
TI  - World Transplant Records--2001. Patients who currently have functioning
      allogeneic transplants.

PMID- 12211789
TI  - Worldwide thoracic organ transplantation: a report from the UNOS/ISHLT
      international registry for thoracic organ transplantation.
AB  - Based on data reported to the UNOS/ISHLT Thoracic and International Registry for
      Thoracic Organ Transplantation: 1. The number of heart transplant operations
      performed in the United States decreased between 1998-1999 and 17 (1%) more
      procedures were performed in 1999 (2,181) than in 2000 (2,198). Sixty-nine more
      lung transplants (an 8% increase) were reported in 2000 than in 1999. 2. Coronary
      artery disease and cardiomyopathy were the most frequently cited indications for
      heart transplantation in the US and have been reported at similar rates during
      the past 10 years. Combined, these diagnoses account for approximately 85% of all
      heart transplants. In 2000, half of all lung transplants were performed for
      emphysema/COPD or alpha-1 antitrypsin deficiency. The most frequently reported
      diagnoses for thoracic transplantation outside the US were: cardiomyopathy (49%)
      for heart, cystic fibrosis (30%) for double lung, emphysema/COPD (34%) for single
      lung and primary pulmonary hypertension (21%) for heart-lung transplants. 3. US
      heart transplant recipients were predominately male (76%), aged 50-64 (51%) and
      white (81%). US lung transplant recipients were also predominately between ages
      50-64 (47%) and white (90%), but unlike heart recipients were more likely to be
      female (51%). No meaningful variance from the US recipient demographic profile
      was noted for the non-US recipients during the same time period. 4. Pediatric
      recipients (< 18 years of age) received 11% of the reported heart transplants and
      6% of the reported lung transplants in the US. 5. Among US thoracic transplant
      recipients during 1999, the one-year survival rates were 84% for heart, 59% for
      heart-lung and 77% for lung. The 5-year survival rates for transplants performed
      during 1995 were: 71% for heart, 56% for heart-lung and 44% for lung transplants.
      6. The long-term patient survival rates were: 23% at 19 years for heart, 16% at
      11 years for lung and 23% at 14 years for heart-lung recipients. 7. During the
      first year after transplantation, 66% of heart recipients and 44% of lung
      recipients did not require rehospitalization. Among those recipients who were
      rehospitalized, the major cause was infection.

PMID- 12211792
TI  - Worldwide Transplant Center Directory. Kidney transplants.

PMID- 12211793
TI  - Worldwide Transplant Center Directory. Kidney/pancreas transplants.

PMID- 12211794
TI  - Worldwide Transplant Center Directory. Pancreas transplants.

PMID- 12211795
TI  - Worldwide Transplant Center Directory. Islet transplants.

PMID- 12211796
TI  - Worldwide Transplant Center Directory. Heart transplants.

PMID- 12211797
TI  - Worldwide Transplant Center Directory. Heart/lung transplants.

PMID- 12211798
TI  - Worldwide Transplant Center Directory. Lung transplants.

PMID- 12211800
TI  - Worldwide Transplant Center Directory. Liver transplants.

PMID- 12211799
TI  - Analysis of United States (US) and non-US pancreas transplants reported to the
      United network for organ sharing (UNOS) and the international pancreas transplant
      registry (IPTR) as of October 2001.
AB  - As of October 10, 2001, > 17,000 pancreas transplant had been reported to the
      IPTR, > 11,500 in the US and > 4,700 outside the US. An era analysis of US cases
      from 1987 to 2001 showed a progressive improvement in outcome (p < 0.04), with
      pancreas transplant graft survival rates (GSRs) going from 75% to 83% at one year
      for SPK cases, from 50% to 78% for PAK cases, and from 49% to 78% for PTA cases.
      The improvements were due both to decreases in technical failure (TF) rates (from
      14% to 7% in SPK, 23% to 8% in PAK, and 23% to 10% in PTA) and immunological
      failure rates (going from 7% to 2% for SPK, from 25% to 2% for PAK, and from 28%
      to 4% for PTA cases). The proportion of recipients > 45 years old increased from
      5% to 25%, and the improved outcomes encompassed the older patients as well. In
      patients > 45 years old, SPK pancreas GSRs at one year increased from 74% to 80%
      (p < 0.007). Pancreas GSRs were also similar for recipients reported to have Type
      1 or Type 2 diabetes (at one year, 84% and 83%, respectively for 1997-2001 SPK
      transplants), the latter designated in 5% of the recipients. Contemporary
      pancreas transplant outcomes were calculated separately for 1997-2001 US and non
      US cases. US patient survival rates at one year were > or = 95% in each recipient
      category, with one year pancreas GSRs of 83% for SPK (n = 3885), 79% for PAK (n =
      630), and 78% for PTA (n = 240) (p = 0.0002). The immunological graft failure
      rates for 1997-2001 US SPK, PAK and PTA cases were 4%, 6%, and 8% at one year (p
      = 0.0001). There was a progressive increase in the use of ED (as opposed to BD)
      for duct management, to 67% for 1997-2001 US SPK transplants, 51% for PAK and 42%
      for PTA. Of US SPK ED transplants, 22% had venous drainage via the portal system.
      US pancreas GSRs were not significantly different for 1997-2001 ED (n = 2,519)
      and BD (n = 1,260) US SPK transplants (82% and 85%, respectively, at one year),
      nor was there a difference in pancreas GSRs for systemic (n = 1,958) versus
      portal (n = 557) venous-drained ED SPK transplants (82% vs. 84% at one year).
      Kidney GSRs were slightly higher for ED versus BD US SPK cases, 93% versus 91% at
      one year (p = 0.03). Duct management did matter for solitary (PAK and PTA)
      pancreas transplants. Pancreas GSRs for PAK recipients were 85% at one year for
      BD (n = 316) versus 74% for ED (n = 303) US transplants (p < 0.02); for PTA 81%
      (n = 168) versus 74% (p > or = 0.37). However, BD transplants were associated
      with a 12% conversion rate to ED by two years posttransplant. Recipient age made
      little difference for outcome in any category. Indeed, in the PTA category GSRs
      were significantly higher for US recipients > 45 years old (n = 66) than 21-45
      years old (n = 216), 85% versus 77% at 1 year (p < or = 0.10). TAC + MMF was the
      dominant maintenance immunosuppressant for 1999-2001 US cases (> 70%). In an
      analysis of outcome according to type of anti-T-cell antibody agents (depleting
      vs. non-depleting vs. none) for induction therapy in TAC + MMF treated
      recipients, there were no differences in GSRs in any of the categories. In regard
      to non-US cases, the overwhelming majority were in the SPK category (n = 1,649
      for 1997-2001), with a one year pancreas GSR of 82%, not significantly different
      than for US cases. In summary, pancreas transplant graft survival rates were
      nearly 80% at one year in recipients of solitary (PAK and PTA) pancreas
      transplants, and > 80% in SPK recipients for 1997-2001 cases. The outcome
      continues to improve as increasing numbers of solitary pancreas transplants are
      done.

PMID- 12211801
TI  - Worldwide Transplant Center Directory. Multi transplants.

PMID- 12211802
TI  - Worldwide Transplant Center Directory. Intestine transplants.

PMID- 12211803
TI  - Worldwide Transplant Center Directory. Stem cell transplants.

PMID- 12211804
TI  - Worldwide Organ Procurement Organization Directory.

PMID- 12211805
TI  - The OPTN waiting list, 1988-2000.
AB  - More patients in the United states are waiting for organ transplants that at any
      time in the past and the remarkable growth of the UNOS waiting list has become a
      key issue for the transplant community. 1. On October 31, 2001, there were
      84,277, registrations on the combined UNOS waiting list. Among these, 63% were
      awaiting kidney transplantation, and 22% were awaiting liver transplantation. 2.
      The majority of patients on the UNOS waiting list on October 31, 2000, were of
      blood type O (52%), white (55%) and male (58%), and awaiting their first
      transplant (87%). 3. The percentage transplanted within one year of listing has
      been declining for most organs, although that percentage has been somewhat stable
      for heart and lung between 1998-2000. 4. Blood type and medical urgency have a
      significant impact upon the percent transplanted within one year of listing for
      most organ types. Patients awaiting heart, pancreas, and intestinal transplants
      experience the highest probability of receiving a transplant within one year. 5.
      Deaths per patients waiting have declined since 1988 for most patients awaiting
      life-saving organs and have remained relatively low for those awaiting a kidney,
      pancreas, or kidney-pancreas transplant. Deaths were highest for lung and heart
      lung patients, but appear to be declining.

PMID- 12211806
TI  - Organ donation in the United States: 1988-2000.
AB  - Based upon information reported to the United Network for Organ Sharing: 1. There
      were 5,985 cadaveric and 5,702 living donors recovered in 2000, a 47% and 213%
      increase, respectively, over those recovered in 1988. 2. The number of cadaveric
      donors aged 50 or older has increased from 12% of all donors in 1988 to 31% of
      all donors in 2000. 3. The typical cadaveric donor in 2000 was a white male with
      ABO blood type O between the ages of 18-34. In 2000, a typical living donor was a
      white female with ABO blood type O between the ages of 35-49. 4. Between 1988
      2000, the percentage of minority donors increased for cadaveric donors (17% to
      26%), and for living donors (24% to 31%). 5. The number of living donors who were
      either spouses or unrelated to the recipient increased from 4% in 1988 to 26% in
      2000. 6. In 2000, California (9.6%) was most often listed as the state of
      residence for cadaveric donors, followed by Texas (7.7%) and Florida (7.3%). 7.
      In 2000, cadaveric donors were recovered most often on Tuesdays (15.0%), followed
      by Thursdays (14.8%) and Fridays (14.7%). 8. In 2000, living donors were
      recovered most often on Wednesdays (27.8%), followed by Tuesdays (26.7%) and
      Thursdays (19.9%). 9. In 2000, cadaveric donors were recovered most often in July
      (9.2%), followed by September (9.0%), January and April (8.7%). 10. In 2000,
      living donors were recovered most often in June (9.5%), followed by November
      (9.2%) and August (9.0%).

PMID- 12211807
TI  - Report from the national transplantation pregnancy registry (NTPR): outcomes of
      pregnancy after transplantation.
AB  - The NTPR continues to analyze the safety of pregnancy in female transplant
      recipients as well as outcomes of pregnancies fathered by male transplant
      recipients. With regard to female recipients, pregnancy does not appear to
      adversely affect graft function, when the function of the transplanted graft is
      stable prior to pregnancy. A small percentage of recipients with each
      transplanted organ develops rejection, graft dysfunction or graft loss. These
      events may occur in recipients with pre-pregnancy graft dysfunction or on
      occasion, occur unpredictably. Female cyclosporine-treated kidney recipients with
      both shorter and longer intervals from transplant to conception have been
      analyzed, with favorable outcomes noted. It appears sensible to continue to
      advise recipients to wait one to 2 years after transplant to allow for stable
      graft function as well as stabilization of immunosuppressive medications.
      However, given that favorable outcomes can occur with either shorter or longer
      intervals, these recipients need to be counseled and followed on a case-by-case
      basis. Newer agents and more potent regimens are under continued surveillance.
      Two cases with structural malformations have been noted in female recipient
      offspring with exposure to MMF during pregnancy. Data remain limited and are
      insufficient to determine a specific malformation incidence. The risk of graft
      rejection as well as graft dysfunction must be weighed against the risk of
      potential teratogenicity when maintaining female recipients on MMF during
      pregnancy. For male recipients maintained on MMF, there have been no patterns of
      problems noted in their offspring. The structural malformation incidence in
      newborn of cyclosporine-treated recipients is in the range expected for the
      general population without any specific predominance of malformations. It remains
      to be seen whether or not any specific pattern of problems will become apparent
      in the newborn with newer regimens. Controversy surrounding breastfeeding
      continues, although it has become an option that some recipients choose to
      consider. Data have accrued in liver, heart, pancreas-kidney and lung recipients.
      Among lung recipients, there appears to be poorer maternal survival postpartum,
      which may be related to pregnancy or may be inherent in this population.
      Continued entries to the registry, especially in light of newer combinations of
      immunosuppressive agents, should help to provide the guidelines for management.
      All centers are encouraged to participate.

PMID- 12211808
TI  - Stuck in the middle again.

PMID- 12211809
TI  - A cut above. Interview by Charlotte Alderman.

PMID- 12211810
TI  - Working wonders. Interview by Charlotte Alderman.

PMID- 12211811
TI  - What nurses really want.

PMID- 12211812
TI  - Beneath the surface.

PMID- 12211813
TI  - Disabled people in hospital: evaluating the CNS role.
AB  - AIM: To evaluate a newly established clinical nurse specialist (CNS) post for
      disabled people in a large acute hospital. METHOD: An action research approach
      was used to collect the data. Information was obtained by speaking to people with
      disabilities, hospital and community staff and voluntary organisations. A
      questionnaire was devised and sent to 38 clients. Of these, 24 were returned.
      Other sources of information included case scenarios from the wards, admissions
      data, nurses' views, diary reflections and feedback from carers. RESULTS: The
      results demonstrated that the CNS role improved the support and information
      clients received before hospital admission. Clients felt less anxious about going
      into hospital. Staff's awareness of disability increased and the training and
      education needs of staff were also identified. CONCLUSION: The action research
      cycle enabled the CNS to identify problem areas in a structured way and to
      implement change through critical self-reflection. Some disabled people are not
      having their needs met in hospital. The main reason for this was a lack of
      awareness among staff about disability. However, the implementation of the CNS
      role improved the care of people with disability and increased staff awareness.

PMID- 12211814
TI  - Older people and nursing: the contemporary agenda.
AB  - The NHS Plan outlines the government's proposals for funding long-term care.
      Pauline Ford presents the RCN's response: although some aspects of the plan are
      welcomed, others need to be addressed before implementation.

PMID- 12211815
TI  - Internet skills for nurses.
AB  - As the internet becomes increasingly accessible to more people, it is important
      to understand its relevance to nursing. Rod Ward discusses its benefits and
      drawbacks, and the need for evaluating web information.

PMID- 12211816
TI  - Students' HIV status leaks are being investigated.

PMID- 12211817
TI  - Career opportunities in childhood cancer nursing.

PMID- 12211818
TI  - Rights and wrongs.

PMID- 12211819
TI  - Lest we forget. Interview by Steven Black.

PMID- 12211820
TI  - Burning issue.

PMID- 12211821
TI  - Control in the community.

PMID- 12211822
TI  - Identifying the knowledge gaps.

PMID- 12211823
TI  - Linking chronic pain and depression.
AB  - BACKGROUND: Patients experiencing chronic pain often seem to develop depression.
      Much research has been carried out into the potential biological, social and
      psychological links between the two. CONCLUSION: Despite the quantity of
      research, this review of the literature reveals that few firm conclusions can be
      drawn from our knowledge to date.

PMID- 12211824
TI  - Urethral catheter selection.
AB  - Many patients undergo urethral catheterisation. Selecting the most appropriate
      catheter for an individual patient requires knowledge and a practical
      understanding of the types of catheter available. A number of factors should be
      considered in catheter selection, including patient needs, indications for
      catheterisation, the type of material, the balloon size and the length and
      diameter of the catheter. The aim of this article is to provide information that
      will clarify some of the concerns nurses might have regarding urethral
      catheterisation.

PMID- 12211826
TI  - The equaliser. Interview by Steven Black.

PMID- 12211825
TI  - Continence in older people: a priority for primary care.
AB  - Many older people experience some form of incontinence and, as a large proportion
      will respond well to treatment, the problem should not be ignored.

PMID- 12211827
TI  - At the heart of nursing.

PMID- 12211828
TI  - Racism in psychiatry.

PMID- 12211830
TI  - Go with the flow.

PMID- 12211831
TI  - Alternative views.

PMID- 12211832
TI  - Clinical nurse managers' perceptions of factors affecting role performance.
AB  - AIM: This study explored clinical nurse managers' perceptions of the factors
      affecting role performance. METHOD: Interviews were carried out with 15 clinical
      nurse managers in four trusts. RESULTS: Results highlight the main influences on
      the role, the barriers to successful role fulfillment, and the stressors that
      cause some of the postholders to consider leaving the NHS. CONCLUSION: The
      findings of this exploratory study established the diversity of the clinical
      nurse manager role and showed that they continue to play a central role in
      healthcare delivery.

PMID- 12211833
TI  - Zero tolerance of violence against healthcare staff.
AB  - A government campaign aimed at stopping violence against healthcare staff is a
      start in dealing with the problem of aggression in the workplace. Staff attitudes
      will also need to be addressed, particularly in those areas where violence has
      become an accepted part of the job, if zero tolerance is to be achieved.

PMID- 12211835
TI  - Assessment of a breathless patient.
AB  - This article discusses a systematic approach to the assessment of a breathless
      patient and outlines the principles of oxygen delivery. The indications for
      oxygen administration, different methods of delivery and the nursing management
      of oxygen therapy are examined.

PMID- 12211834
TI  - Fast-tracking older people through A&E.
AB  - This article explores the concept and feasibility of fast-tracking older people
      through A&E services to enable appropriate admission and quality responsive
      patient care. It illustrates how an academic assignment undertaken as part of a
      pre-registration programme could be adapted for publication to challenge thinking
      and encourage examination of potential new ways of working.

PMID- 12211836
TI  - Waiting in vain.

PMID- 12211837
TI  - Hard times. A better deal is on the way for long-term care residents, but home
      owners fear for their future.

PMID- 12211838
TI  - Smooth operator. Interview by Catharine Sadler.

PMID- 12211839
TI  - Share deal. Interview by Pat Healy.

PMID- 12211840
TI  - Full marks for effort.

PMID- 12211841
TI  - Take ME seriously.

PMID- 12211843
TI  - Safety in numbers.

PMID- 12211844
TI  - A private matter.

PMID- 12211845
TI  - 'Under 16s get pregnant too'.

PMID- 12211846
TI  - Mouth to mouth.

PMID- 12211848
TI  - Nurse prescribing: what do patients think?
AB  - AIM: To explore nurse prescribing from the patient's viewpoint. METHOD: This
      study was undertaken in one primary care group in Leicestershire. All prescribing
      health visitors (n = 17), district nurses (n = 9) and practice nurses (n = 1)
      were asked to recruit five patients for whom they had prescribed. Fifty patients
      took part in a telephone or face-to-face interview. Participants were
      predominantly low or new users of nurse prescribing, while the nurse prescribers
      were experienced. RESULTS: Participants identified that nurse prescribers had key
      skills in assessment, observation, diagnosing and providing information. Nurse
      prescribing was accepted by all participants as a practical and responsive method
      of service delivery. Gains identified were better use of the nurse's and doctor's
      time, convenience, a quality relationship with the nurse and expertise of the
      nurse. Disadvantages identified included the limitations of the Nurse
      Prescribers' Formulary and the training and competence of nurse prescribers.
      CONCLUSION: This study helps affirm that nurse prescribers meet the needs of
      patients, with positive experiences in terms of the process and outcomes. Future
      developments suggested by participants appear to reflect government concerns.
      Such changes include the need to develop and maintain competence to uphold public
      safety and for the formulary to be expanded. To ensure that the NHS workforce is
      used more effectively, participants agreed with providing patient-centred
      services and the renegotiation of traditional roles.

PMID- 12211849
TI  - Education for nurses returning to practice.

PMID- 12211850
TI  - Syringe pumps and start-up time: ensuring safe practice.
AB  - The start-up time is the delay between starting an infusion pump and the delivery
      of fluid at the set flow rate. Mechanical slack in syringe pumps can lead to
      start-up delays of an hour or more at low-flow rates. During this period no
      medication is delivered to the patient. The causes of the start-up time delay,
      its implications and methods of minimising the delay are explained.

PMID- 12211852
TI  - Learning about sex. Interview by Chris Mayer.

PMID- 12211851
TI  - The pressures felt by informal carers of people with dementia.
AB  - Caring for people with dementia is complex and demanding, and informal carers
      carry out much of the care. In this article, Madeline Armstrong outlines the
      different types of dementia and discusses the psychological approaches to care.
      Informal carers experience many stressors when caring for people with dementia
      and Admiral nurses play an important role in supporting carers.

PMID- 12211853
TI  - Soya elixir.

PMID- 12211854
TI  - Moving picture.

PMID- 12211855
TI  - Crisis management.

PMID- 12211856
TI  - Perceptions of racism in the health service.
AB  - AIM: The information reported in this article formed part of a large study, which
      examined how the pre-registration nursing curriculum prepares students to work
      with minority ethnic groups. Questions on racism were asked as a subsidiary to
      the main area under study. METHOD: A questionnaire was sent to student nurses (n
      = 1035) and lecturers (n = 303) teaching pre-registration students in the North
      West Region. Participants were also invited to record their qualitative comments.
      RESULTS: The results showed that a higher percentage of lecturers than students
      had heard what they perceived to be racist comments in the classroom. Several
      students commented that racist attitudes were mainly the result of a lack of
      knowledge and/or ignorance. CONCLUSION: From the study results, it appears that
      racism is still evident in the classroom and the clinical placement area.

PMID- 12211857
TI  - An audit of care planning on a neurology unit.
AB  - Care planning is an important aspect of nursing care. Carol Kirrane discusses the
      use of an audit tool to improve patient care planning within a neurology unit.
      The use of this audit tool has led to more patient-focused, individualized and
      holistic care planning by nurses.

PMID- 12211858
TI  - Improving practice with a nurse nutrition team.
AB  - This article describes how the introduction of a nurse nutrition team has led to
      improved staff morale and communication, as well as increasing the number of
      appropriate referrals to the dietician.

PMID- 12211860
TI  - Persistence pays off. Interview by Charlotte Alderman.

PMID- 12211859
TI  - Nutritious, enjoyable food in nursing homes.
AB  - Mary Clay describes ways in which nurses should ensure that patients in nursing
      homes receive appropriate dietary care.

PMID- 12211861
TI  - Blurred vision.

PMID- 12211863
TI  - Assault v discipline.

PMID- 12211864
TI  - Better continence management.

PMID- 12211865
TI  - Applying collaborative practice to health promotion.
AB  - BACKGROUND: Since the publication of the Health of the Nation document in 1992,
      collaborative practice has been at the forefront of health service reform. While
      other professional groups have readily adopted health promotion and
      collaboration, the nursing profession has experienced difficulties in changing
      practice and some have resisted reform. The author examines the issues
      surrounding nursing's apparent hesitancy in adopting collaborative working
      practices. CONCLUSION: To promote collaborative practice, nurses need to be aware
      of the range of teams and agencies involved in health promotion and acknowledge
      the client as an equal member of the team. However, better education, training
      and shared learning initiatives are essential to improve collaborative practice.

PMID- 12211866
TI  - Developing multidisciplinary profiles in a day hospital.
AB  - The Ferguson Day Hospital provides a patient-centred, multidisciplinary service
      for patient assessment and rehabilitation. The authors describe the development
      of a patient profile that has centralised documentation and reflects the
      multidisciplinary nature of the services provided.

PMID- 12211867
TI  - Sharing the care of children with HIV infection.
AB  - Providing shared care for children with HIV infection can improve their quality
      of life. Jo White explores some of the issues that arise when the care of HIV
      infected children is shared between a specialist centre and a local district
      general hospital. Factors that are important for successful shared care are
      discussed.

PMID- 12211868
TI  - Making sense of cancer.
AB  - Nurses caring for patients with cancer do so at varying stages of the disease
      trajectory from diagnosis to death. Having an understanding of cancer biology,
      potential causes and classification should enable you to understand the treatment
      options and to communicate more effectively with patients, their families and
      friends.

PMID- 12211869
TI  - A rebirth in standards.

PMID- 12211870
TI  - Age-old practices.

PMID- 12211871
TI  - Support service.

PMID- 12211872
TI  - A rationale for oral care.
AB  - BACKGROUND: Although oral hygiene is an essential aspect of care for every
      patient admitted to hospital (Jenkins 1989, Watson 1989), it would appear that
      oral care procedures are not based on research evidence but on tradition,
      anecdotal evidence and subjective assessments. This article reviews the research
      evidence for oral care to identify best practice. CONCLUSION: There is
      substantial literature on mouth care, but research does not substantiate current
      methods of oral care. Research-based education on mouth care should be promoted
      within the nursing curricula.

PMID- 12211873
TI  - Reflective practice in thermoregulatory nursing care.
AB  - This article demonstrates how the use of a reflective model can aid organisation
      and rationalisation of thoughts that, in turn, results in improved nursing care
      of patients with fever.

PMID- 12211874
TI  - PICC securement: minimising potential complications.
AB  - Peripherally inserted central catheters are used for a variety of parenteral
      therapies. This article discusses the advantages of securing these catheters and
      different methods of securement.

PMID- 12211875
TI  - The use of intravenous therapy.
AB  - Nurses have a professional and legal responsibility to understand the rationale
      for the use of prescribed fluids. Safe administration requires an understanding
      of the role of electrolytes and water and of the mechanisms of movement between
      different body compartments.

PMID- 12211876
TI  - Repairing the bodyworks.

PMID- 12211877
TI  - The role of pharmaceutical companies in research and development--plaudits and
      cautions.

PMID- 12211878
TI  - Diagnostic concepts and the prevention of schizophrenia.

PMID- 12211879
TI  - Understanding predisposition to schizophrenia: toward intervention and
      prevention.
AB  - OBJECTIVE: Early intervention to prevent schizophrenia is one of the most
      important goals of schizophrenia research. However, the field is not yet ready to
      initiate trials to prevent prodromal or psychotic symptoms in people who are at
      risk for developing the disorder. In this paper, we consider some of the major
      obstacles that must be studied before prevention strategies become feasible.
      METHOD AND RESULTS: One of the most important hurdles is the identification of a
      syndrome or set of traits that reflects a predisposition to schizophrenia and
      that might provide potential targets for intervention. In a recent reformulation
      of Paul Meehl's concept of schizotaxia, we integrate research findings obtained
      over the last 4 decades to propose a syndrome with meaningful clinical
      manifestations. We review the conceptualization of this syndrome and consider its
      multidimensional clinical expression. We then describe preliminary research
      diagnostic criteria for use in adult, nonpsychotic, first-degree relatives of
      patients diagnosed with schizophrenia, based on negative symptoms and
      neuropsychological deficits. We follow this with evidence supporting the validity
      of the proposed syndrome, which mainly includes social dysfunction and response
      to a low dosage of one of the newer antipsychotic medications. CONCLUSIONS:
      Continued progress toward the eventual initiation of prevention strategies for
      schizophrenia will include sustained efforts to validate the traits reflecting a
      predisposition to develop the disorder (for example, schizotaxia), follow-up
      studies to confirm initial findings, and the identification of potentially useful
      preventive interventions.

PMID- 12211880
TI  - Preventing schizophrenia and psychotic behaviour: definitions and methodological
      issues.
AB  - Although schizophrenia onset usually occurs in late adolescence or early
      adulthood, much research shows that its seeds are planted early in life and that
      eventual onset occurs at the end of a neurodevelopmental process leading to
      aberrant brain functioning. This idea, along with the fact that current therapies
      are far from fully effective, suggests that preventive treatments may be needed
      to achieve an ideal outcome for schizophrenia patients and those predisposed to
      the disorder. In this article, we review the methodological challenges that must
      be overcome before effective preventive interventions can be created. Prevention
      studies will need to define the target population. This requires the
      identification of risk factors that will be useful in selecting at-risk people
      for preventive treatment. We review currently identified risk factors for
      schizophrenia: genes, psychosocial factors, pregnancy and delivery complications,
      and viruses. We also review 3 different types of prevention programs: universal,
      indicated, and selective. For schizophrenia, we distinguish prevention programs
      that target prodromal cases and those that target the disorder's premorbid
      precursors. Although those targeting prodromal cases provide a useful framework
      for early treatment of the disorder, studies of premorbid individuals are needed
      to design a truly preventive treatment.

PMID- 12211881
TI  - Association of QEEG findings with clinical characteristics of OCD: evidence of
      left frontotemporal dysfunction.
AB  - OBJECTIVE: Our objectives were 1) to determine hemispheric asymmetry and regional
      differences on the EEGs of patients with obsessive-compulsive disorder (OCD); and
      2) to investigate the effects of sex, treatment response, illness duration, and
      Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores on quantitative
      electroencephalographic (QEEG) measurements. METHOD: We recorded EEGs (12
      channel) from 22 unmedicated patients with OCD but no depression and from 20 age-
      and sex-matched control subjects. All patients and control subjects underwent
      detailed neurological and psychiatric evaluations including the Hamilton
      Depression Rating Scale (HDRS) and Y-BOCS. RESULTS: QEEG revealed higher
      frequencies of slow-wave bands and lower frequencies of alpha activity at
      predominantly left frontotemporal localization in patients with OCD, compared
      with control subjects. Analysis of variance of QEEG parameters and clinical
      characteristics showed that sex had a significant effect on delta and alpha
      frequencies of frontotemporal areas during hyperventilation (HV). Increasing
      total Y-BOCS score correlated positively with increased frequencies of right
      parietal delta activity and decreased frequencies of right frontotemporal alpha
      activity during HV. A significantly increased left frontal slow-wave activity and
      decreased beta activity during HV in treatment responders led us to consider that
      frontal lobe functions were better in this group of patients. Illness duration
      had no important effect on QEEG. CONCLUSION: Patients with OCD showed important
      frontotemporal dysfunction, predominantly in the left hemisphere. This was
      particularly evident in female subjects and in treatment responders. QEEG may be
      beneficial in understanding the neurobiological basis of OCD.

PMID- 12211882
TI  - Ecstasy and drug consumption patterns: a Canadian rave population study.
AB  - OBJECTIVE: This study investigates the drug consumption patterns of a sample of
      rave attendees in the city of Montreal, Quebec, and seeks to identify the
      prevalence of 3,4-methylendioxymethamphetamine (MDMA) and other drug use in this
      population. METHOD: We administered a self-report questionnaire to 210
      respondents. For various licit and illicit substances, participants reported
      their age of first use, number of lifetime uses, and usage in the previous 30
      days. RESULTS: We found a significant rank order for the sequence of first use:
      1) alcohol, 2) nicotine, 3) cannabis, 4) LSD, 5) psilocybin, 6) amphetamine, 7)
      cocaine, 8) MDMA, 9) gamma-hydroxybutyrate (GHB), 10) ephedrine, 11) ketamine.
      Alcohol and cannabis were the most commonly used substances, both in cumulative
      number of lifetime uses and in usage in the preceding 30 days. MDMA and
      amphetamine were also notable as the next 2 most popular drugs for use in the
      preceding 30 days and in terms of those who had tried the drugs at least once. We
      identified a progressive rank order of experimentation, with early alcohol or
      cannabis use (or both) associated with the early use of all other drugs tried by
      more than 25% of the sample. We found MDMA and amphetamine use to be prevalent,
      as was general experimentation with all drugs studied, other than heroin.
      CONCLUSION: Drug consumption levels were substantial in this "rave" population,
      particularly with respect to recent use of MDMA, amphetamine, cannabis, and
      alcohol. Results also indicate that the sequence of drug experimentation in this
      population follows an identifiable pattern.

PMID- 12211883
TI  - The 2 "Es" of research: efficacy and effectiveness trials.
AB  - Studies that investigate the usefulness of various therapies fall along a
      continuum that ranges from those looking at whether an intervention can work
      under ideal circumstances (efficacy trials) to those that focus on whether a
      treatment works when applied in the real world (effectiveness trials). Whether a
      study is closer to one end of the spectrum or the other affects almost every
      aspect of the trial. These aspects include which patients are eligible for
      enrollment, the degree of control over the way the intervention is delivered,
      which patients are or are not included in the analyses, how missing data are
      handled, and even which statistical tests may be used. The 2 types of trials may
      yield different results, but both provide useful information. This paper explores
      these issues, shows the decisions researchers must take at each phase of a trial,
      and discusses how clinicians should interpret the results.

PMID- 12211884
TI  - Serum cholesterol level comparison: control subjects, anxiety disorder patients,
      and obsessive-compulsive disorder patients.
AB  - OBJECTIVE: To determine whether panic disorder is associated with elevated serum
      cholesterol levels. Serum cholesterol levels of panic disorder patients are
      reported to be elevated. This could explain the higher-than-expected
      cardiovascular mortality in this population. Some evidence exists wherein
      cholesterol levels are also increased in patients with general anxiety disorder
      and phobias. To date, there are only 2 reports on cholesterol levels of obsessive
      compulsive disorder (OCD) patients, giving controversial results. METHOD: We
      compared serum cholesterol levels of anxiety disorder patients, OCD patients, and
      normal control subjects with each other (n = 60 in each group). Serum cholesterol
      was measured in each subject before treatment. Subjects of the 3 groups were
      matched by age and sex. RESULTS: Patients with anxiety disorders and OCD had
      elevated cholesterol levels, compared with normal control subjects. Cholesterol
      levels in OCD patients were comparable with those in patients with phobia.
      CONCLUSIONS: Our data support the assumption that elevation in cholesterol level
      is not a specific feature of panic disorder (as most assumed), but more generally
      associated with anxiety disorders. Increased cholesterol levels in patients with
      anxiety disorders and OCD may be of clinical relevance.

PMID- 12211885
TI  - Perceptions of intimidation in the psychiatric educational environment in
      Edmonton, Alberta.
AB  - OBJECTIVE: To examine the perceptions of intimidation in the psychiatric
      educational environment in Edmonton, Alberta. METHODS: We distributed a 7-point
      modified Likert scale questionnaire that included questions with respect to
      intimidation perceptions and experience in psychiatry during a 1-week period to
      all student interns on psychiatry rotations, residents, and teaching faculty in
      the 5 teaching hospitals in Edmonton. RESULTS: A total of 92 individuals
      responded, with response rates of 81% for faculty, 82% for residents, and 84% for
      students. Response rates did not differ among sites. While there were differences
      between site and group with respect to comparing the perceived intimidation in
      psychiatry with other specialties, respondents did not view psychiatry as worse
      than other specialties. Although, overall, women perceived intimidation as more
      prevalent at their sites than did men, the overall means reflect sites that are
      relatively free from intimidation. Faculty and student interns within sites,
      except for the university hospital, tended to disagree on management's approach
      to perceived intimidation. All groups, however, reported little personal
      experience and felt their sites had little tolerance for intimidators.
      CONCLUSIONS: Reported perceptions and personal experiences of intimidation within
      the psychiatric learning environment in Edmonton are low.

PMID- 12211886
TI  - Senior residents in psychiatry: views on training in developmental disabilities.
AB  - OBJECTIVES: To determine the proportion of senior residents who believed their
      education in the field of developmental disabilities was adequate and to collect
      suggestions for improvements. METHOD: We distributed a self-administered
      questionnaire to senior residents prior to an annual voluntary preparatory exam.
      Their views on training in developmental disabilities and ideas about improving
      curricula were solicited in detail, and their feedback results were analyzed.
      RESULTS: Of the 89 senior residents who attended the exam, 60 (67.4%) completed
      the survey. This represents 29% of the national complement. Most (85%) of the one
      half who reported receiving undergraduate training in developmental disabilities
      felt the quantity was inadequate. Almost 90% of those who did not receive
      training felt they should have. Of respondents, 85% received residency training
      in dual diagnosis, but most (59%) felt more curriculum time was needed.
      CONCLUSIONS: Senior residents also desire curricular enhancements that experts in
      developmental disabilities have long recommended.

PMID- 12211887
TI  - Evidence that latitude is directly related to variation in suicide rates.
AB  - OBJECTIVE: To use available suicide-rate data from 20 countries to see patterns
      and relations more clearly. METHOD: We obtained raw suicide rates from the
      Organization for Economic Cooperation and Development (OECD) database from 1960
      through 1997 and calculated averages and standard deviations. RESULTS: There is a
      positive linear relation between the variation in suicide rate and geographic
      latitude. CONCLUSIONS: The variation in light-dark cycles is superimposed upon
      human mood.

PMID- 12211888
TI  - Massive weight gain and hostility force mirtazapine stoppage.

PMID- 12211889
TI  - Functional dyspepsia and mirtazapine.

PMID- 12211890
TI  - Re: Using language in psychiatry.

PMID- 12211891
TI  - Psychotic mania in bipolar II depression related to sertraline discontinuation.

PMID- 12211892
TI  - [Delirium associated with azithromycin administration].

PMID- 12211893
TI  - Behavioural therapy for the treatment of alcohol abuse and dependence.

PMID- 12211894
TI  - Study of HLA-DR expression on skin lesions of leprosy before and during multiple
      drug therapy.
AB  - Leprosy is a dynamic disease in which cell mediated immunity (CMI) plays an
      important role in host defense and control of the clinical spectrum. This study
      was carried out to detect immune activation in the granuloma of leprosy during
      multiple drug therapy (MDT) by studying the expression of human leukocytic
      antigen-DR (HLA-DR) in the granuloma before and during therapy. Skin punch
      biopsies were taken before and at least once 2-4 weeks after starting MDT in 20
      newly diagnosed patients. Two biopsies, 2-4 weeks apart, were also taken from 10
      new patients who did not yet receive any treatment, for comparison. Furthermore,
      biopsies were taken before and during corticosteroid therapy in five patients who
      developed reversal reaction during MDT. The biopsy specimens were studied for the
      expression of HLA-DR using the immunofluorescent staining which was found to be
      visibly increased in 17 out of 20 new cases (85%) within 2-4 weeks after starting
      MDT, while no change in the expression was noticed in those who did not receive
      any treatment (p < 0.001). This might reflect the increased production of
      interferon gamma (IFN gamma) specially from granuloma lymphocytes after being
      stimulated with the excessive release of mycobacterial antigen from killed
      bacilli during therapy. The five patients who developed reversal reaction during
      MDT had strong HLA-DR expression in the first biopsies which declined
      subsequently 2-6 weeks after starting prednisolone therapy. Our results suggest
      that CMI was activated in skin lesions of leprosy during MDT. Such activation was
      not only restricted to those who developed reversal reaction across the
      therapeutic course, which indicates that the difference between patients who
      developed such reaction and those who did not, was likely to be quantitative
      rather than qualitative, with a more exaggerated CMI response in the former.
      Furthermore, it seems that the beneficial effect of MDT is accompanied by
      important changes in the immune cell profile which have a great role in
      overcoming such infection.

PMID- 12211895
TI  - Contrary to BCG, MLM fails to induce the production of TNF alpha and NO by
      macrophages.
AB  - Pathogenic mycobacteria must possess efficient survival mechanisms to resist the
      harsh conditions of the intraphagosomal milieu. In this sense, Mycobacterium
      lepraemurium (MLM) is one of the most evolved intracellular parasites of murine
      macrophages; this microorganism has developed a series of properties that allows
      it not only to resist, but also to multiply within the inhospitable environment
      of the phagolysosome. Inside the macrophages, MLM appears surrounded by a thick
      lipid-envelope that protects the microorganism from the digestive effect of the
      phagosomal hydrolases and the acid pH. MLM produces a disease in which the loss
      of specific cell-mediated immunity ensues, thus preventing activation of
      macrophages. In vitro, and possibly also in vivo, MLM infects macrophages without
      triggering the oxidative (respiratory burst) response of these cells, thus
      preventing the production of the toxic reactive oxygen intermediaries (ROI).
      Supporting the idea that MLM is within the most evolved pathogenic
      microorganisms, in the present study we found, that contrary to BCG, M.
      lepraemurium infects macrophages without stimulating these cells to produce
      meaningful levels of tumor necrosis factor alpha (TNF alpha) or nitric oxide
      (NO). Thus, the ability of the microorganisms to stimulate in their cellular
      hosts, the production of ROI and RNI (reactive nitrogen intermediates), seems to
      be an inverse correlate of their pathogenicity; the lesser their ability, the
      greater their pathogenicity.

PMID- 12211896
TI  - Irrational use of skin-bleaching products can delay the diagnosis of leprosy.

PMID- 12211897
TI  - Uveitis seen in the long clinical course of leprosy.

PMID- 12211898
TI  - Ninhydrin sweat test in the early detection of leprosy.

PMID- 12211899
TI  - Regarding Mohamed, facial lesions resembling to leprosy.

PMID- 12211900
TI  - Study of pattern of ocular changes in different types of leprosy patients.

PMID- 12211901
TI  - Serum monocyte chemoattractant protein-1 is elevated in lepromatous leprosy
      patients with high bacterial indices.

PMID- 12211903
TI  - Should nursing posts be sponsored commercially?

PMID- 12211902
TI  - MR imaging of neuropathic feet in leprosy patients with suspected osteomyelitis.
AB  - This study was undertaken to analyze MRI findings in leprosy patients with
      neuropathic feet, which are suspected of having osteomyelitis. As far as we know,
      there is no literature concerning osteomyelitis and MRI in neuropathic leprosy
      feet at present. Therefore, we have included MRI examination of 18 events of
      suspected osteomyelitis in 12 leprosy patients. All patients with long-standing
      neuropathic foot problems were clinically suspected of having osteomyelitis. All
      patients underwent the MRI protocol with the inclusion of Two Point Dixon
      Chemical Shift Imaging as a fat-suppression sequence. For the MRI evaluation, we
      used signs that are described in literature for detecting osteomyelitis in
      diabetic feet. The primary MRI signs were positive in 17 of 18 patients. The
      secondary MRI signs were positive in 100% of the patients. Our results show that
      MRI with the use of Two Point Dixon Chemical Shift Imaging is a promising
      diagnostic modality to detect osteomyelitis in the presence of
      neurosteoarthropathic changes in patients with leprosy. Whenever available, MRI
      could play an important role in detecting osteomyelitis in leprosy patients with
      long-standing neuropathic feet.

PMID- 12211904
TI  - Pull no punches with serial bullies.

PMID- 12211905
TI  - Bullies, back off.

PMID- 12211907
TI  - Coming along swimmingly.

PMID- 12211906
TI  - 10 steps to personal power.

PMID- 12211908
TI  - Kissing companion.

PMID- 12211909
TI  - Cancer care. Part 1. Mental health care for women with breast cancer.
AB  - Women with breast cancer often experience anxiety and depression related to their
      diagnosis, treatment and prognosis. A collaborative project was set up by a
      breast care nurse and a liaison psychiatric nurse after they detected a gap in
      the services on offer to these women. Their initiative uses an established
      assessment tool to detect potential mental health problems and a patient pathway
      to ensure that the women's needs are monitored and met throughout their illness.

PMID- 12211910
TI  - Extended prescribing: the legal implications.
AB  - The number of nurses with prescribing powers is increasing and the potential
      legal implications of this extended responsibility are not yet known. This
      article describes the development of nurse prescribing, from the Crown reports
      and the government's responses to them to the most recent moves to extend nurses'
      prescribing powers. It also examines whether enhanced prescribing
      responsibilities are likely to place nurses at increased risk of litigation.

PMID- 12211911
TI  - Interdisciplinary work in community mental health.
AB  - The idea of mental health and social care staff working within clearly defined
      roles is often frowned upon as poor and retrogressive practice, out of step with
      the government's modernisation agenda. But as this article points out,
      increasingly blurred roles in already stressful and demanding clinical teams can
      be counterproductive, with practitioners becoming entrenched in their own
      perception of their particular roles and less flexible in their work. Conversely,
      well-defined boundaries and clearly defined roles can be supportive and enabling,
      providing a containing structure for teams to work within.

PMID- 12211912
TI  - Integrating health care services for older people.
AB  - A review of inpatient and community services for older people in Liverpool
      revealed that although quality services were being provided, this was only to a
      limited number of patients. The tracker nurses' role at this stage was to
      determine the factors that resulted in the emergency readmission of patients aged
      over 65 and attempt to prevent this. Eight months later the team began to focus
      on extending its services to a wider patient group by screening all emergency
      admissions and inpatients at a local acute hospital. The team compiled action
      plans for patients with complex needs, enabling discharge planning to begin as
      soon as possible after admission and ensuring that the needs of patients
      requiring intermediate care were met quickly. The average number of transfers to
      intermediate care trebled as a result of this change in focus.

PMID- 12211913
TI  - Sharing good practice in the care of older people.
AB  - Good nursing care, informed by best practice, is an integral part of achieving
      positive health outcomes for older people. The first article in a two-part series
      on gerontological nursing discusses collaboration between higher education and
      clinical practice which aims to improve practice in the specialty. It outlines
      the development of a Scottish project that promoted such an exchange of
      information by holding regular forums. The project has been a success and it is
      hoped that it will lead to the establishment of a centre of excellence for
      gerontological care. Next week's article focuses on the shared approach to care.

PMID- 12211914
TI  - Cardiopulmonary resuscitation. Advisory defibrillation--2.

PMID- 12211915
TI  - Nurse prescribing and pain management.

PMID- 12211916
TI  - Management of chronic pain.

PMID- 12211917
TI  - Elderly care nurses' knowledge.

PMID- 12211918
TI  - Making sense of epidural analgesia.

PMID- 12211919
TI  - Day in the life.

PMID- 12211920
TI  - Overview of outcomes research: state of the art.

PMID- 12211921
TI  - Qualitative research in diabetes: the role of stories in the culture of science.

PMID- 12211922
TI  - The certified diabetes educator and the pedorthist working together.

PMID- 12211923
TI  - Effective strategies for reaching high-risk minorities with diabetes.
AB  - The NDOP goals of enhancing diabetes awareness by increasing screening activities
      within select African American neighborhoods and involving residents in health
      promotion activities were met during the course of the project. The coalition
      focused on principles suggested for diabetes programs directed at African
      American communities, including involving a target audience, providing a service,
      empowering people, and respecting cultural diversity. The focus group mechanism
      facilitated the input of community members into the program design prior to
      implementation and insured their involvement throughout the project. The
      screening and education program fostered empowerment by increasing community
      residents' control, focusing on their strengths, and identifying personal health
      goals. Funding support from the New York State Department of Health and the
      American Association of Diabetes Educators' Research Foundation were both
      essential in implementing the program. The program was well received. Most of the
      participant evaluations rated the program as excellent or very good. The program
      sites, although demographically situated within identified African American
      communities, produced a greater number of Caucasian and Hispanic participants
      than expected. Although the older group of African American women constituted 25%
      of the total population screened, it did not reach the desired number of 300
      participants. Future programs need to target sites where older African American
      women are more likely to be found in greater numbers. Key to the program's
      success was building strong partnerships with community leaders who served as
      cultural spokespersons for the initiative to ensure participation from the
      community. Developing this partnership proved to be more challenging than
      originally anticipated and required a respectful, persevering approach. Yet once
      the coalition achieved cohesion, the volunteer members were invaluable in
      planning and implementing program events. Community members eventually took
      charge of the coalition and organized programs that have extended beyond the 2
      year period of the grant. The coalition continues to expand; members have been
      added and education programs at churches and community meetings are ongoing.
      Addressing the problem of diabetes in African American communities requires
      programs that are innovative, culturally and educationally appropriate, and
      presented regularly. Such ongoing efforts can increase the knowledge in African
      American communities and ultimately enhance the health outcomes of community
      members.

PMID- 12211924
TI  - An educator's guide to the diabetes outcomes measurement systems.

PMID- 12211925
TI  - Development and validation of a literacy assessment tool for persons with
      diabetes.
AB  - PURPOSE: This research was conducted to develop a valid, reliable, quick, and
      nonstigmatizing tool for assessing literacy in the healthcare setting. METHODS:
      The Literacy Assessment for Diabetes (LAD) instrument was developed as a word
      recognition test composed of 3 graded word lists in ascending difficulty. This
      literacy test, which was specific to diabetes, measured a patient's ability to
      pronounce terms that they would encounter during clinic visits and in reading
      menu and self-care instructions. The majority of the terms were on a 4th-grade
      reading level, with the remaining words ranging from the 6th-through 16th-grade
      levels. To assess reliability and validity, the LAD was compared with the Wide
      Range Achievement Test (WRAT3) and the Rapid Estimate of Adult Literacy in
      Medicine (REALM) by administering all 3 tests to 203 participants in a test
      retest study design. RESULTS: All 3 tests (LAD, REALM, and WRAT3) reliably
      detected true intrasubject variation in word recognition from test to retest. In
      addition, LAD measured word recognition ability similar to the REALM and WRAT3.
      CONCLUSIONS: The LAD is a reliable and valid instrument for measuring literacy in
      adults with diabetes. It can be administered in 3 minutes or less, and the raw
      score is scaled to a reading grade level.

PMID- 12211926
TI  - Development of the diabetes problem-solving measure for adolescents.
AB  - PURPOSE: This paper describes the development and psychometric properties of the
      Diabetes Problem-Solving Measure for Adolescents (DPSMA). METHODS: The DPSMA is a
      structured, interview-based questionnaire that examines how adolescents with type
      1 diabetes solve diabetes-related self-management problems. Seventeen diabetes
      related self-management problem vignettes were derived from a survey of
      adolescents and their parents. The vignettes were reviewed and finalized by a
      multidisciplinary team of diabetes experts. A sample of 43 adolescents, 13 to 17
      years old, with type 1 diabetes, was used to establish the psychometric
      properties of the instrument. RESULTS: The scale demonstrated acceptable internal
      consistency and interrater reliability. Predicted relationships with scores on
      concurrently administered measures of adherence, diabetes quality of life, and
      metabolic control provided support for construct validity. CONCLUSIONS: The
      results suggest that the DPSMA has acceptable internal consistency, interrater
      reliability, and construct validity. It may be a useful tool to help healthcare
      providers understand the diabetes-related problem-solving abilities of their
      adolescent patients.

PMID- 12211927
TI  - A diabetes-specific measure of patient desire to participate in medical decision
      making.
AB  - PURPOSE: The goal of this study was to develop a diabetes-specific scale of
      patient desire to participate in medical decision making (DPMD) and examine its
      internal consistency reliability, stability, and validity (content, discriminant,
      convergent, and construct). METHODS: In a cross-sectional study, 65 patients with
      type 2 diabetes from a teaching hospital's general medical clinic were
      interviewed at baseline and 2 weeks later to measure their DPMD scores. Data were
      collected on demographic/clinical features, health value, social support, desire
      to make a final decision, and value of patient autonomy. RESULTS: Of the 11 DPMD
      items, 2 distinct factors emerged representing desire for discussion and desire
      for information. The DPMD scale had high internal consistency reliability, was
      stable over 2 weeks and demonstrated good content validity. DPMD scale items were
      more correlated with each other than with health value or social support.
      Overall, patients who obtained diabetes education reported greater desire to
      participate in decisions. Younger patients had a greater overall desire for
      discussion. The DPMD desire for discussion subscale correlated with patients'
      desire to make the final treatment decision but not with patients' value of
      autonomy. CONCLUSIONS: The DPMD is a brief, reliable, valid measure for assessing
      patient desire to participate in diabetes medical decision making.

PMID- 12211928
TI  - The content, integrity, and efficacy of a nurse coaching intervention in type 2
      diabetes.
AB  - PURPOSE: The purpose of this study was to systematically evaluate the content,
      integrity, and efficacy of a nurse coaching intervention provided after diabetes
      education that focused on dietary and exercise lifestyle change in persons with
      type 2 diabetes. METHODS: A multimethod design incorporated an interpretive
      approach to examine the content and integrity of the intervention and a multiple
      baseline, single-subject method to determine the preliminary efficacy of the
      intervention. RESULTS: The primary strategies of the nurse coaching intervention
      consisted of facilitating lifestyle change through educational reinforcement,
      psychosocial support, and motivational guidance. Aggregate quantitative outcomes
      revealed a modest increase in health-promoting behaviors and a decrease in
      fasting blood glucose, indicating a trend toward physiologic adaptation.
      Participants demonstrated a significant increase in integration reflective of
      psychosocial adaptation. CONCLUSIONS: Providing individualized nursing care after
      diabetes education may improve health outcomes and the quality of life of persons
      newly diagnosed with type 2 diabetes. This multimethod design is a cost-effective
      approach for preliminary evaluation of complex and/or novel interventions.

PMID- 12211929
TI  - Toward a research agenda for the American Association of Diabetes Educators.

PMID- 12211930
TI  - A study of forearm versus finger stick. Blood glucose monitoring.

PMID- 12211931
TI  - Special delivery. Interview by Lynne Pearce.

PMID- 12211932
TI  - Championing the cause.

PMID- 12211933
TI  - Dressing for effect.

PMID- 12211934
TI  - Control freakery.

PMID- 12211935
TI  - Uniforms: a comparative evaluation of tunic tops.
AB  - AIM: The aim of this study was to produce a recommendation for selection of a
      tunic top for female nurses, based on previously established ergonomic criteria.
      METHOD: Four tunic top designs were evaluated using functional tests, including
      anthropometry, body-part discomfort charts, product feature questionnaires and
      comparative ranking. A convenience sample of nurses from one trust wore the
      tunics during the study tests. The trial draws heavily on previous research on
      nurses' uniforms and applies ergonomic criteria to tunic top design. RESULTS: The
      researchers were not able to identify on optimum design using the results of the
      trial. The tunics compared were relatively restrictive, with one tunic being
      identified as the least restrictive of the four. CONCLUSION: The researchers are
      now taking this initiative forward in a participatory ergonomics project with
      nursing staff to try to produce a uniform design that will meet functional
      ergonomic criteria. Prototypes will be evaluated using the protocol from this
      trial.

PMID- 12211936
TI  - The role of the CNS in head and neck oncology.
AB  - This article provides an insight into the development of the first clinical nurse
      specialist (CNS) post in head and neck oncology in Northern Ireland. The author
      reflects on her personal experience of the benefits and the difficulties in the
      first year of practice. Although the article focuses on head and neck cancer
      services, the concepts can be applied to setting up specialist nursing services
      in other specialties.

PMID- 12211937
TI  - Non-steroidal anti-inflammatory drugs: clinical issues.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) include aspirin, ibuprofen and
      diclofenac. They are widely prescribed to control pain and inflammation
      associated with disease or injury affecting joints and other tissues. The authors
      describe the clinical uses, mechanism of action and potential side effects.
      Paracetamol/acetaminophen is included in this discussion, although it is not an
      NSAID.

PMID- 12211938
TI  - Crisis? What crisis?

PMID- 12211939
TI  - The pill: still swinging at 40.

PMID- 12211940
TI  - Two generations. Family planning nurses have provided support to decades of young
      women in need of contraception and advice.

PMID- 12211941
TI  - Making a difference. Interview by Lynne Pearce.

PMID- 12211942
TI  - Netting good advice.

PMID- 12211943
TI  - Don't expect miracles.

PMID- 12211944
TI  - Health care, epilepsy and learning disabilities.
AB  - There is a high incidence of epilepsy among people with learning disabilities.
      However, there is no comprehensive strategy for epilepsy care and little research
      is carried out into health issues and learning disabilities.

PMID- 12211945
TI  - Regulation of water, sodium and potassium: implications for practice.
AB  - Regulation of fluid balance is a complex subject. Sharon Edwards discusses the
      physiological principles involved.

PMID- 12211946
TI  - Clinical governance and pressure ulcer management.
AB  - The government has introduced a framework for clinical governance as a means to
      promote high quality services for patients. Caroline Dowsett discusses the
      importance of adopting a positive approach to clinical governance within pressure
      ulcer management.

PMID- 12211947
TI  - Sitting: pressure ulcer development.
AB  - Seating is a major factor in pressure ulcer development, but it is frequently
      overlooked in the literature on pressure area management. Pressure ulcers are
      largely preventable and nurses are integral to the promotion of good practice.
      The author examines how implementing careful patient assessment, correct
      positioning and providing optimum seating equipment can help to reduce the risk
      of pressure ulcer development.

PMID- 12211948
TI  - Wound debridement: evaluating the costs.
AB  - Debridement is the technique used to remove slough and necrotic tissues that can
      prevent or delay wound healing. The authors compare the published evidence on the
      speed and cost-effectiveness of larval therapy with that of more conventional
      dressings used to promote autolytic wound debridement.

PMID- 12211949
TI  - Compression therapy in leg ulcer management.
AB  - Leg ulcer management is an important consideration for all nurses involved in the
      care of older people. Non-specialists in tissue viability might not always be
      aware of the evidence base for best practice. The authors examine the
      effectiveness of multilayer and single-layer long- or short-stretch bandage
      systems in leg ulcer management.

PMID- 12211950
TI  - Children in need.

PMID- 12211951
TI  - World class service.

PMID- 12211952
TI  - Driving change. Interview by Catharine Sadler.

PMID- 12211953
TI  - Abandoned but not alone. Interview by Mary Hampshire.

PMID- 12211954
TI  - Walk-in wonderland.

PMID- 12211955
TI  - Language barrier.

PMID- 12211957
TI  - Right to life.

PMID- 12211958
TI  - Confidence boost.

PMID- 12211960
TI  - Self-administration of medicine and older people.
AB  - BACKGROUND: Non-adherence to medication regimens is a significant problem in
      older patients, which can lead to therapeutic failure and the wastage of
      resources. Common causes include poor patient memory, physical difficulties,
      unpleasant side effects and a lack of social support. CONCLUSION: Strategies such
      as careful labelling, self-administration of medicine programmes, simplifying
      drug regimens and the use of medication compliance devices can help to promote
      patient adherence. Some of these interventions will work for certain patients,
      however the authors recommend that a multidisciplinary assessment and a regular
      review of each patient's ability to adhere to medication should be undertaken.

PMID- 12211962
TI  - HIV-positive students can still train.

PMID- 12211961
TI  - Type 2 diabetes in children.
AB  - The prevalence of type 2 diabetes mellitus is increasing in children and is
      reaching epidemic proportions in some western countries. Sue Howdle and Terry
      Wilkin examine the extent of the problem, the disease process, screening,
      prevention and management of type 2 diabetes.

PMID- 12211964
TI  - Diverse practice.

PMID- 12211963
TI  - Deep vein thrombosis: clinical nursing management.
AB  - The occurrence of a deep vein thrombosis is potentially life threatening and
      rapid assessment and treatment are essential to prevent development of a
      pulmonary embolism. Prophylaxis and risk assessment are important aspects of DVT
      management.

PMID- 12211965
TI  - Don't leave it to chance.

PMID- 12211966
TI  - The state of medical education in Texas.

PMID- 12211967
TI  - Compensation planning in academic medicine.

PMID- 12211968
TI  - State funding of academic medical centers in Texas: where does graduate medical
      education fit?

PMID- 12211969
TI  - Development of a rural training track for Texas.
AB  - Rural areas in Texas constitute a major portion of the state. Health care access
      and distribution issues in rural areas are recognized on many levels, from the
      local community with limited resources or facing the loss of a critical health
      care professional to the Texas Medical Association and Texas state government.
      Rural training tracks are one way to provide family medicine residents with the
      knowledge, skills, and attitudes necessary for successful practice in rural
      areas. Building collaborative relationships between rural physicians and
      university-based residency programs, as described in this project, may offer one
      solution to the problem of medically underserved rural communities in Texas.

PMID- 12211970
TI  - Community-based medical education: two campuses, one faculty, one school.

PMID- 12211971
TI  - Patient safety and medical education: a partnership for the future.

PMID- 12211972
TI  - The true story of pertussis vaccination: a sordid legacy?

PMID- 12211973
TI  - Alexander the Great, seafaring, and the spread of leprosy.

PMID- 12211974
TI  - The Association of Hygieia with Asklepios in Graeco-Roman Asklepieion medicine.

PMID- 12211975
TI  - The Lancett Club at a Thurtell Feast, by Thomas Rowlandson.

PMID- 12211976
TI  - Simultaneous catalytic removal of NOx and diesel soot particulate over perovskite
      type oxides and supported Ag catalysts.
AB  - A series of perovskite-type oxides and supported Ag catalysts were prepared, and
      characterized by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy
      (XPS). The catalytic activities of the catalysts as well as influencing factors
      on catalytic activity have been investigated for the simultaneous removal of NOx
      and diesel soot particulate. An increase in catalytic activity for the selective
      reduction of NOx was observed with Ag addition in these perovskite oxides,
      especially with 5% Ag loading. This catalyst could be a promising candidate of
      catalytic material for the simultaneous elimination of NOx and diesel soot.

PMID- 12211977
TI  - Continuous treatment of azo acid dyes by photo-dependent denitrifying sludge.
AB  - Simultaneous removals of dye and nitrate by photo-dependent denitryfying
      sludge(PDDS) have been demonstrated in a continuous-flow bench-scale reactor. The
      best C/N for the degradation of azo dyes by PDDS was 1.5. The specific removal
      rate of azo dye AB92 decreased with a decrease in hydraulic retention time and
      increased with a decrease in solids retention time. The degradation rate of TOC
      decreased with a decrease in hydraulic retention time. AB92, which has nitro and
      hydroxyl substitutions in non-para positions, was uniquely degraded. During
      continuous flow treatment experiments using PDDS, complete degradation of azo
      dyes AB92 and AO20 at influent concentrations of 40 mg/L and 30 mg/L,
      respectively, was achieved with an HRT of 16.

PMID- 12211978
TI  - Excavation and characterization of refuse in closed landfill.
AB  - Refuse in landfills becomes stabilized as organic matter in refuse degrades and
      soluble inorganic substances dissolve during their long-term stabilization
      process. In this paper, this process is also referred to as mineralization
      process and the resultant stabilized refuse referred to as aged refuse. Aged
      refuse contains a wide spectrum and huge quantity of microorganisms with strong
      decomposition capability for refractory organic matter present in some wastewater
      such as leachate. In this study, aged refuse excavated from 2 to 10 years old
      closed landfill compartments in Shanghai Refuse Landfill is characterized in
      terms of particulate distribution by screening, total nitrogen, total phosphorus,
      biodegradable matter. The approaches for redevelopment of both land and aged
      refuse in the stabilized landfills are proposed.

PMID- 12211979
TI  - Impact of triazophos insecticide on paddy soil environment.
AB  - A laboratory incubation study was carried out to elucidate the dynamic response
      of insecticide (triazophos) on a paddy field soil health under controlled
      moisture (flooded soil) and temperature (25 degrees C). The insecticide was
      applied at five levels that were 0.0 (control), 0.5 field rate (FR), 1.0 FR, 5.0
      FR, and 10.0 FR, where FR was 1500 ml/hm2, and the parameters were studied at 1,
      4, 7, 14, and 21 days after treatments' addition. The electron transport system
      (ETS)/dehydrogenase activity exhibited a negative correlation with insecticide
      concentrations, and the activity affected adversely as the concentration
      increased. The higher doses of 5 and 10 field rates significantly reduced the ETS
      activity, while lower rates failed to produce any significant inhibiting effect
      against the control. The toxicity of insecticide decreased towards decreasing the
      ETS activity with the advancement of incubation period. The insecticide caused an
      improvement in the soil phenol content and it increased with increasing
      concentration of insecticide. The insecticide incorporation applied at various
      concentrations did not produce any significant change in soil protein content and
      it remained stable throughout the incubation period of 21-days. The response of
      biomass phospholipid content was nearly similar to ETS activity. The phospholipid
      content was decreased with the addition of insecticide and the toxicity was in
      the order: 10 FR (field rate) > 5 FR > 1.0 FR > 0.5 FR > control and it also
      decreased with incubation period.

PMID- 12211980
TI  - Experimental analysis of a nitrogen removal process simulation of wastewater land
      treatment under three different wheat planting densities.
AB  - Nitrogen contaminant transport, transformation and uptake simulation experiments
      were conducted in green house under three different planting density of winter
      wheat. They were Group A, planting density of 0.0208 plants/cm2, Group B, 0.1042
      plants/cm2, and Group C, 0.1415 plants/cm2. The capacity and ratio of nitrogen
      removal were different on three kinds of conditions of wastewater land treatment.
      From analysis of wastewater treatment capacity, wastewater concentration and
      irrigation intensity for Group C were suitable and nitrogen quantity added was 2
      times of that for Group B, 2.6 times for Group A while nitrogen residue was only
      7.06%. Hence, wastewater irrigation and treatment design with purpose of waste
      water treatment should select the design with maximum capacity, optimal removal
      ratio and least residue in soil, which was closely related to crop planting
      density, crop growth status and also background nitrogen quantity in soil.

PMID- 12211981
TI  - Spatial variations of Pb in the vertical zone of the soil-plant system in the
      Changbai Mountain National Nature Reserve.
AB  - The characteristics of vertical and horizontal variations of lead element(Pb) in
      soil-plant system of vertical zone in Changbai Mountain National Nature
      Reserve(CNNR) were studied. The results showed that Pb concentrations in soils of
      vertical zone are all above 25 mg/kg, and the average Pb concentration of each
      soil zone negatively correlates its degree of variation, i.e. brown coniferous
      forest soil zone has the lowest average Pb concentration of four soil zones, and
      the highest horizontal variation; however, mountain soddy forest soil has the
      highest average Pb concentration, and the lowest horizontal variation; the
      average concentration of plant Pb of each plant zone is lower than the worldwide
      average level of Pb in plant(Clarke), respectively, and plant Pb content order is
      consistent with soil Pb content order, but their horizontal variations are
      different from those in soil zones, the variation of mountain tundra forest zone
      is highest, but Betula ermanii forest zone the lowest. Vertical variation of
      plant Pb is obviously higher than that in soils with variation coefficient of
      89.76%; the enrichment capability of plant for Pb is depended on the plant types
      and the different organs of plant; parent material and parent rock, pH values,
      soil organic matter and soil particle fraction etc. are the main factors
      influencing variations of Pb content in soil-plant system of vertical zone in
      CNNR.

PMID- 12211982
TI  - The affect of industrial activities on zinc in alluvial Egyptian soil determined
      using neutron activation analysis.
AB  - Thirty-two surface (0-20 cm) soil samples were collected from different locations
      in Egypt representing non-polluted, moderately and highly polluted soils. The aim
      of this study was to evaluate total Zn content in alluvial soils of Nile Delta in
      Egypt by using the delayed neutron activation analysis technique (DNAA), in the
      irradiation facilities of the first Egyptian research reactor (ET-RR-1). The
      gamma-ray spectra were recorded with a hyper pure germanium detection system. The
      well resolved gamma-ray peak at 1116.0 keV was efficiently used for 65Zn content
      determination. Zn content in non-polluted soil samples ranged between 74.1 and
      103.8 ppm with an average of 98.5 +/- 5.1 ppm. Zn content in moderately polluted
      soils ranged between 136.0 and 232.5 ppm with an average of 180.1 +/- 32.6 ppm.
      The highest Zn levels ranging from 240.0 and 733.0 ppm with an average of 410.3
      +/- 54.4 ppm, were observed in soil samples collected from, either highly
      polluted agricultural soils exposed to prolonged irrigation with industrial
      wastewater or surface soil samples from industrial sites.

PMID- 12211983
TI  - On the minimum cost of an evolutionary strategy response to environment stress.
AB  - Two revised drafts about a simple evolution trade-off function studied by
      Mitchell(Mitchell, 2000) were put up first. Considering the complex of the
      environment, or the nonlinear interaction of the environment and species, we put
      up two new cost functions: [formula: see text] In the first case, if the
      environment is adverse to species (a > 0), the region of low-stress which is more
      suitable for the intolerant species is very small, and at the same environment
      stress z, the tolerant species will pay the more cost than it will paid in the
      normal environment. However the tolerant species will pay more cost but low
      strategies in the environment of a < 0 than that it will paid in the environment
      of a = 0 or a > 0. In the second case, the results showed that the greater the
      stress of the environment is, or the more complex the environment is, the lower
      cost the intolerant species will pay in the region of z < 1. In order to exist or
      to evolve from an environment of high-stress, the organisms must possess a higher
      u, or a better means of mitigating of the stress of environment. Meanwhile in the
      region d > 1, when d decrease, the intolerant species will pays more lower cost
      of exploiting a habitat in the low-stress environment while the tolerant one will
      pays more lower cost in the high-stress environment. This means that scale d
      describes the selection character of the species system in the evolution process,
      the smaller the d(d < 1) is, the better the selection or the mitigation the
      system will possesses.

PMID- 12211984
TI  - Phytosynthetic bacteria (PSB) as a water quality improvement mechanism in saline
      alkali wetland ponds.
AB  - The efficiency of phytosynthetic bacteria (PSB) to improve the water quality in
      saline-alkali ponds was studied, the result showed that (1) PSB application could
      increase the content of DO, NO3-(-)N and effective phosphorus (EP) in ponds; (2)
      the changes of COD were not evident, just effective in later period after PSB
      application; (3) PSB application could decrease the contents of NH4-(-)N (NH3-N),
      NO2-(-)N; (4) PSB application could improve the structure of the effective
      nitrogen (EN) and EP, stimulate the growth of phytoplankton, and increase primary
      productivity, and finally increase the commercial profits of ponds because of the
      increase of EP and the decrease of EN contents; (5) the effect-exerting speed of
      PSB was slower, but the effect-sustaining time was longer; (6) the appropriate
      concentration of PSB application in saline-alkali wetland ponds was 10 x 10(-6)
      mg/L, one-time effective period was more than 15 days. So PSB was an efficient
      water quality improver in saline-alkali ponds.

PMID- 12211985
TI  - Preparation of PFS coagulant by sectionalized reactor.
AB  - The oxidation rate of ferrous sulfate is investigated for the preparation of
      polyferric sulfate (PFS) coagulant. It is proved that this reaction is zero order
      with respect to Fe2+, first order with respect to NO2(g), and first order with
      respect to the interface area between gas phase and liquid phase. According to
      this mechanism, sectionalized reactor(SR) is used in place of traditional reactor
      (TR), and the liquid of reaction mixture is recycled by pump. As a result, not
      only the flow path of reaction liquid is prolonged, but also gas-liquid contact
      area enlarged, and the reaction distinctly accelerated, compared with traditional
      reactor. The effects of parameters including temperature, acidity and others on
      the reaction rate are also discussed.

PMID- 12211986
TI  - Characteristics of the natural organic matter sorption affects of organic
      contaminants.
AB  - Several soil samples were used to study how the characteristics of natural
      organic matter (NOM) affect sorption of organic compounds. These soils contains
      different amounts and types of NOM. Aromaticity of NOM (percentage of aromatic
      carbons) was determined from solid-state CPMAS 13C NMR spectra and the soil
      effective polarity was computed from the equation developed by Xing et al.
      Naphthalene was used to examine the sorption characteristics of NOM. Both
      aromaticity and polarity of NOM strongly affected sorption of naphthalene. Old
      NOM showed higher affinity than that in the surface, young soils. Sorption
      increased with increasing aromaticity and decreasing polarity. Thus, the sorption
      coefficients of organic contaminants cannot be accurately predicted without some
      consideration of NOM characteristics.

PMID- 12211987
TI  - Agricultural sustainability in a sensitive environment--a case analysis of Loess
      Plateau in China.
AB  - Loess Plateau, an arid and semi-arid region in Northwest China, is well-known for
      its most serious soil erosion in terms of sediment yield each year. Soil erosion,
      which is intensified by agricultural activities, is the major factor influencing
      sustainable agriculture development in this region. It reduces productivity by
      removing nutrients and especially reducing water availability that is essential
      for crop production in the area. It also brings about off-site costs by demanding
      more efforts for maintenance of banks and dams along Yellow River through raising
      the riverbed with sediment. Climate is capricious and extreme weather conditions
      occur frequently, which impairs normal agricultural production with erosion and
      also decrease of water availability. Extensive way of farming still dominates on
      the Loess Plateau, which cannot produce satisfying economic results and needs to
      be improved or altered. Conventional agricultural production pattern needs to be
      reconsidered for husbandry has not been granted its due position. Agriculture is
      the backbone of economy. Poor agricultural production impedes economic
      development and vice versa, backward economy also influences the advancement of
      agriculture. Besides a large population, education status of farmers is another
      threshold that requires being resolved for a sustainable agriculture. Although
      conventional agriculture has been practiced there for more than 5000 years, now
      it cannot meet the demand for food and fiber by the increasing population and
      some of its farming practices are contributing to environmental degradation
      directly or indirectly and can sustain no longer. Agriculture on Loess Plateau
      needs to find its own way of sustainability. To work toward a sustainable
      agriculture, chances and challenges both indwell on Loess Plateau.

PMID- 12211988
TI  - A genetic algorithm based stochastic programming model for air quality
      management.
AB  - This paper presents a model that can aid planners in defining the total allowable
      pollutant discharge in the planning region, accounting for the dynamic and
      stochastic character of meteorological conditions. This is accomplished by
      integrating Monte Carlo simulation and using genetic algorithm to solve the
      model. The model is demonstrated by using a realistic air urban-scale SO2 control
      problem in the Yuxi City of China. To evaluate effectiveness of the model,
      results of the approach are shown to compare with those of the linear
      deterministic procedures. This paper also provides a valuable insight into how
      air quality targets should be made when the air pollutant will not threat the
      residents' health. Finally, a discussion of the areas for further research are
      briefly delineated.

PMID- 12211989
TI  - Removal of copper from a copper sulphate solution using an ultrasonic
      electrolysis process.
AB  - The application of ultrasonic-electrolysis process for the removal of copper is
      studied. In the ultrasonic field cavitation acts as jets and agitates the
      solution and breaks the barrier layer between the cathode surface and the bulk of
      the solution. Thus increases metal deposition on the cathode surface. The results
      show that an ultrasonic field is successful for the removal of low copper
      concentrations in solution.

PMID- 12211990
TI  - Vegetation patterns and nature reserve construction in an extremely-arid desert
      in Anxi, NW China's Gansu Province.
AB  - Anxi County is located in the northwestern part of the Hexi Corridor in Gansu
      Province and has the sole national level nature reserve of extremely-arid desert
      in China. Phytosociological methods (Braun-Blanquet, 1964) are used to classify
      plant community types in this area. Eleven are distinguished, including six of
      deserts, four of cases and one transitional type between deserts and cases.
      Direct gradient analysis (DCA) is employed to correlate the distribution of plant
      communities to physiogeographic conditions. This study makes clear that water is
      the most important ecological factor for the distribution of plant species and
      communities in this area. The effects of water have been demonstrated in
      different ways. A vegetation gradient from lower altitude to higher altitude in
      the southern part of the reserve is driven by a precipitation gradient. The
      effects of the depth of ground water table contribute to the differentiation of
      vegetation from desert to oasis in the flat area. In a finer scale, the washed
      gullies have obviously higher species richness and also higher vegetation cover
      than the surround gobi surfaces, possibly caused by the effects of floods. The
      vegetation patterns demonstrate that the area of Anxi County is a complete
      landscape unit. The range of the current nature reserve is not large enough for
      the purpose of conserving the unique biodiversity in this area.

PMID- 12211991
TI  - Photo-assisted fenton oxidation of refractory organics in UASB-pretreated
      leachate.
AB  - Nearly 91% of organic pollutants in Hong Kong leachate could be effectively
      removed by the UASB (upflow anaerobic sludge blanket) process followed by the
      fenton coagulation. The COD (chemical oxygen demand) of leachate was lowered from
      an average of 5620 mg/L to 1910 mg/L after the UASB treatment at 37 degrees C,
      and was further lowered to 513 mg/L after fenton coagulation. The remaining
      refractory residues could be further removed by photochemical oxidation with the
      addition of H2O2. The BOD/COD ratio was greatly increased from 0.062 to 0.142,
      indicating the biodegradability of organic residues was improved. The
      photochemical oxidation for the fenton-coagulation supernatant was most effective
      at pH 3-4, with the addition of 800 mg/L of H2O2, and UV radiation time of 30
      minutes. The final effluent contained only 148 mg/L of COD, 21 mg/L of BOD
      (biochemical oxygen demand) and 56 mg/L of TOC (total organic carbon).

PMID- 12211992
TI  - Effect of hydrodynamic characteristics on reaeration process.
AB  - The equilibrium-perturb technique was used in the flume reaeration experiment.
      The interfacial mass transfer coefficients of DO were obtained by implementation
      of the oxygen-flux theory in the study. The turbulence characteristics of the
      flow field were investigated by numerical simulation approach. The expression of
      interfacial mass transfer coefficient related with velocity and turbulence
      kinetic energy was built. Examination with the experimental datum of different
      cases showed the validation of the expression.

PMID- 12211993
TI  - Differences of cadmium absorption and accumulation in selected vegetable crops.
AB  - A pot experiment and a sandy culture experiment grown with three vegetable crops
      of Chinese cabbage (B. chinensis L., cv. Zao-Shu 5), winter greens (B. var.
      rosularis Tsen et Lee, cv. Shang-Hai-Qing) and celery (A. graveolens L. var.
      dulce DC., cv. Qing-Qin) were conducted, respectively. The initial soil and four
      incubated soils with different extractable Cd (0.15, 0.89, 1.38, 1.84 and 2.30 mg
      Cd/kg soil) were used for the pot experiment. Five treatments were designed (0,
      0.0625, 0.125, 0.250 and 0.500 mg Cd/L) in nutrient solution in the sandy culture
      experiment. Each treatment in pot and sandy culture experiments was
      trireplicated. The objectives of the study were to examine Cd accumulation in
      edible parts of selected vegetable crops, its correlation with Cd concentrations
      in vegetable garden soil or in nutrient solution, and evaluate the criteria of Cd
      pollution in vegetable garden soil and in nutrient solution based on the hygienic
      limit of Cd in vegetables. Cadmium concentrations in edible parts of the three
      selected vegetable crops were as follows: 0.01-0.15 mg/kg fresh weight for
      Chinese cabbage, 0.02-0.17 mg/kg fresh weight for winter greens, and 0.02-0.24
      mg/kg fresh weight for celery in the pot experiment, and 0.1-0.4 mg/kg fresh
      weight for Chinese cabbage, 0.1-1.4 mg/kg fresh weight for winter greens, and
      0.05-0.5 mg/kg fresh weight for celery in the pot experiment (except no-Cd
      treatment). The order of the three test vegetable crops for cadmium accumulation
      in the edible parts was celery > winter greens > Chinese cabbage in both the pot
      experiment and the sandy culture experiment. Cadmium accumulation in edible parts
      or roots of the vegetable crops increased with increasing of cadmium
      concentration in the medium (soil or nutrient solution). And cadmium
      concentrations in edible parts of the test vegetable crops were significantly
      linearly related to the Cd levels in the growth media (soil and nutrient
      solution). Based on the regression equations established and the limit of cadmium
      concentration in vegetable products, the thresholds of Cd concentration in the
      growth medium evaluated was as follows: 0.5 mg/kg soil of extractable Cd for soil
      and 0.02 mg/L for nutrient solution. The high capacity for cadmium accumulation
      in the edible parts of different vegetable crops together with the absence of
      visual symptoms implies a potential danger for humans.

PMID- 12211994
TI  - Effect of leachate recycling and inoculation on the biochemical characteristics
      of municipal refuse in landfill bioreactors.
AB  - Activity development of key groups of enzymes involved in municipal refuse
      decomposition was measured in laboratory landfill bioreactors with and without
      leachate recycling and inoculation for about 210 days. The results showed that
      the enzymes (amylase, protease, cellulase, lipase and pectinase) were present in
      fresh refuse but at low values and positively affected by leachate recycling and
      refuse inoculation. The total average of cellulase activity in digesters D3
      operated with leachate recycling but no inoculation, D4 and D5 operated with
      leachate recycling and inoculation was much higher than that in digesters D1 and
      D2 without leachate recycling and inoculation by 88%-127%, 117%-162% and 64%-98%.
      The total average of protease activity was higher in digester D4 than that in
      digesters D1, D2, D3 and D5 by 63%, 39%, 24% and 24%, respectively, and the
      positive effect of leachate recycling and inoculation on protease activity of
      landfilled refuse mainly was at the first two months. The total average of
      amylase activity was higher in digesters D3, D4 and D5 than that in digesters D1
      and D2 by 83%-132%, 96%-148% and 81%-129%. During the early phase of incubation,
      the stimulatory effect of inoculation on lipase activity was measured, but refuse
      moisture was the main factor affecting lipase activity of landfilled refuse. The
      inoculation, initial and continuous inoculation of microorganisms existing in
      leachate, was the mainly stimulatory factor affecting pectinase activity of
      landfilled refuse.

PMID- 12211995
TI  - Effects of butachlor on microbial enzyme activities in paddy soil.
AB  - This paper reports the influences of the herbicide butachlor (n-butoxymethl
      chloro-2', 6'-diethylacetnilide) on microbial respiration, nitrogen fixation and
      nitrification, and on the activities of dehydrogenase and hydrogen peroxidase in
      paddy soil. The results showed that after application of butachlor with
      concentrations of 5.5 micrograms/g dried soil, 11.0 micrograms/g dried soil and
      22.0 micrograms/g dried soil, the application of butachlor enhanced the activity
      of dehydrogenase at increasing concentrations. The soil dehydrogenase showed the
      highest activity on the 16th day after application of 22.0 micrograms/g dried
      soil of butachlor. The hydrogen peroxidase could be stimulated by butachlor. The
      soil respiration was depressed within a period from several days to more than 20
      days, depending on concentrations of butachlor applied. Both the nitrogen
      fixation and nitrification were stimulated in the beginning but reduced greatly
      afterwards in paddy soil.

PMID- 12211996
TI  - Quantitative structure retention relationship studies for predicting relative
      retention times of chlorinated phenols on gas chromatography.
AB  - A new method of quantitative structure-retention relationship (QSRR) studies was
      reported for predicting gas chromatography (GC) relative retention times (RRTs)
      of chlorinated phenols (CPs) using a DB-5 column. Chemical descriptors were
      calculated from the molecular structure of CPs and related to their gas
      chromatographic RRTs by using multiple linear regression analysis. The proposed
      model had a multiple square correlation coefficient R2 = 0.970, standard error SE
      = 0.0472, and significant level P = 0.0000. The QSRR model also reveals that the
      gas chromatographic relative retention times of CPs are associated with
      physicochemical property interactions with the stationary phase, and influenced
      by the number of chlorine and oxygen in the CP mOlecules.

PMID- 12211997
TI  - Reversed flow injection spectrophotometric determination of low residuals of
      chlorine dioxide in water using chlorophenol red.
AB  - A novel, simple, rapid, sensitive and highly selective flow injection procedure
      for the spectrophotometric determination of chlorine dioxide in the presence of
      other chlorine species, viz, free chlorine, chlorite, chlorate and hypochlorite,
      is developed. The method is based on the discoloration reaction between chlorine
      dioxide and chlorophenol red and can overcome the shortcomings existed in direct
      spectrophotometric determination for chlorine dioxide owing to the serious
      interference of free and combined chlorine. The procedure gave a linear
      calibration graph over the range 0-0.71 mg/L of chlorine dioxide. With a
      detection limit of 0.024 mg/L and a sample throughput of 60 samples/h.

PMID- 12211998
TI  - Photocatalytic degradation of PCP-Na with TiO2 photocatalysis loaded with
      platinum.
AB  - Titanium dioxide (TiO2) samples of different crystal forms were prepared by
      hydrolysis tetrabutyl titanate in various water to alkoxide ratios and sintering
      the hydrolysis product at different temperatures. The photocatalysts coated on
      hollow glass beads and loaded with platinum varying from 0.2% to 2.4% by weight.
      The photocatalytic degradation rate of sodium pentachlorophenolate (PCP-Na)
      depends on the preparing conditions such as: sintering temperatures, water to
      alkoxide ratios (R), platinum content and the size. The proper conditions of
      preparation photocatalysts are as follows: the ratio of TiO2: sodium silicate:
      hollow glass beads: platinum is 10:5:20:0.15 (w/w), R is 100, sintering
      temperature is 650 degrees C, and the size of hollow glass is 0.5-1 mm. Under
      these conditions, the ratio between acatase and rutile of the photocatalyst is
      2:1, and the photocatalytic activity is high.

PMID- 12211999
TI  - European Convention on Human Rights: effects on psychiatric care.
AB  - The introduction of the European Convention on Human Rights into UK law will have
      a direct effect on practice in mental health care. The authors discuss
      developments associated with the Convention, examine different articles and
      suggest the changes they could bring. They suggest that, rather than reacting to
      the development of convention rights, healthcare professionals should take the
      opportunity to influence new standards for psychiatric care.

PMID- 12212000
TI  - Childhood immunisation.
AB  - There is much debate surrounding the topic of immunisation. Helen McCarthy
      discusses the immunisation process with an emphasis on risk assessment.

PMID- 12212001
TI  - Understanding and managing cellulitis.
AB  - Cellulitis is a relatively common emergency in acute and community care settings,
      and can be a source of significant pain and anxiety for affected patients. This
      article examines the management of patients with generalised cellulitis--an
      infection of the skin and subcutaneous tissues, which is exacerbated by the
      presence of damaged skin, poor circulation or diabetes mellitus. Appropriate
      dressing regimens for the management of wounds resulting from this infection are
      discussed. Localised cellulitis that develops as a result of an existing wound
      infection is not covered in this article.

PMID- 12212002
TI  - Surgical wound management: the role of dressings.
AB  - The history of surgical wound management illustrates how dressings have evolved
      over the years and sets the scene for modern wound-healing products. The aim of
      this article is to discuss the management of surgical wounds and the value of
      wound-healing products for carers and patients in the current healthcare climate
      of cost-efficacy and clinical governance.

PMID- 12212003
TI  - Use of Doppler ultrasound in leg ulcer assessment.
AB  - Adequate patient assessment is the most important element of chronic wound
      management, and the use of holistic techniques enables practitioners to make
      informed clinical judgements. Doppler ultrasound is integral to the holistic
      assessment of leg ulcers. This article reviews the procedure for measuring
      ankle/brachial pressure indices using Doppler ultrasound and outlines various
      diagnostic tests that employ the Doppler principle.

PMID- 12212004
TI  - Yellow card.

PMID- 12212005
TI  - Island life. Interview by Steven Black.

PMID- 12212006
TI  - Prescription for change.

PMID- 12212007
TI  - Blood technique.

PMID- 12212008
TI  - Perceptions of men's sexual health behaviour.
AB  - AIM: The aim of the pilot study was to explore lay and professional perceptions
      of men's sexual health behaviour and the factors affecting risk in relation to
      sexually transmitted infection (STI). METHOD: The research was conducted in two
      cities in the UK and data were collected using a semi-structured questionnaire. A
      purposive sampling technique was used to ensure that a mixture of lay and
      professional responses was received. RESULTS: The results indicate that lay and
      professional respondents perceive that STI risk is related to social inequality.
      Men from minority ethnic groups and lower social classes are believed to be at
      particular risk of contracting STIs but their needs are not being adequately
      addressed by sexual health services and information providers. CONCLUSION:
      Further research is needed to discover the ways in which sexual health and risk
      are affected by social inequality. Service providers and planners need to
      consider the possible consequences of developing sexual health services for the
      male population.

PMID- 12212009
TI  - Helping patients with tinnitus: guidance for nurses.
AB  - It is no longer necessary for people with tinnitus to suffer, as self-help
      strategies are available. Nurses are in a position to provide information about
      tinnitus and help people to manage their condition. This article gives guidance
      for nurses produced by the British Tinnitus Association.

PMID- 12212011
TI  - Keep it on the record.

PMID- 12212010
TI  - HIV and AIDS: an overview.
AB  - Despite a decrease in deaths due to AIDS in industrialised nations, there is
      still much confusion surrounding HIV and AIDS. The authors provide an up-to-date
      overview.

PMID- 12212012
TI  - Imagine imaging.

PMID- 12212013
TI  - The clinical importance of postprandial hyperglycemia.

PMID- 12212014
TI  - Addressing religion and spirituality in African Americans with diabetes.

PMID- 12212015
TI  - Ten tips for becoming a certified diabetes educator.

PMID- 12212016
TI  - Patient perceptions of prandial oral therapy for type 2 diabetes.
AB  - PURPOSE: This survey was conducted to assess patient perceptions of glycemic
      control, convenience, and flexibility of a prescribed prandial oral therapy for
      type 2 diabetes mellitus. METHODS: Questionnaires distributed by physicians
      yielded baseline responses from 3696 patients who were beginning repaglinide
      treatment. Data were analyzed from 1233 respondents who also completed follow-up
      questionnaires after 4 weeks of treatment. RESULTS: Among respondents, 60% were
      taking repaglinide with other antidiabetic agents in combination therapy; 59%
      were taking metformin, and 24% were taking troglitazone. Most respondents (84%)
      indicated that they were "satisfied" or "very satisfied" with repaglinide
      therapy, 92% wished to continue its use, and 60% believed that the treatment had
      improved their attitude toward taking antidiabetic medication. Patients perceived
      that fasting blood glucose levels were reduced during treatment, as was the
      incidence of hyperglycemia. Corresponding changes in perceived frequency of
      hypoglycemia during repaglinide treatment were minimal. CONCLUSIONS: Patient
      perceptions of prandial oral therapy with repaglinide were predominantly
      positive, due mostly to the perception that glucose control was achieved, with
      minimal perception of any increase in hypoglycemic episodes.

PMID- 12212017
TI  - Perceived difficulty of diabetes treatment in primary care: does it differ by
      patient ethnicity?
AB  - PURPOSE: The purpose of this cross-sectional study was to determine the attitudes
      of internal medicine physicians toward treating diabetes in different patient
      ethnic groups and compared with treating common chronic medical conditions in
      primary care. METHODS: The survey instrument was administered to 55 internal
      medicine physicians. An e-mail message was sent to each physician with a
      hyperlink to a site where the survey could be completed. The instrument was a
      modified, quantitative 10-point scale designed to measure attitudes regarding the
      difficulty of treating diabetes. RESULTS: Diabetes was perceived to be more
      difficult to treat than hyperlipidemia and angina. African Americans with
      diabetes were perceived to be more difficult to treat than Caucasian patients.
      Difficulty in treating diabetes was comparable to that for hypertension,
      arthritis, and congestive heart failure. Physicians were confident about
      treatment efficacy for diabetes and changing diabetes outcomes, but not about the
      adequacy of time and resources for diabetes treatment. CONCLUSIONS: Diabetes was
      perceived as a difficult disease to treat, African American patients were more
      difficult to treat, and time and resources were inadequate for diabetes
      treatment. To improve diabetes care, there is a need to address these attitudes
      and concerns of internal medicine physicians.

PMID- 12212018
TI  - Heuristic model linking contextual processes to self-management in African
      American adults with type 2 diabetes.
AB  - PURPOSE: This article examines the influence of various environmental factors on
      the diabetes self-care practices of African American adults with type 2 diabetes.
      METHODS: A heuristic model was developed that considers how community barriers
      and supports, availability and use of insurance, diabetes education, medical
      provider-patient relationships, extended family processes, and psychological
      functioning may indirectly affect metabolic control through the patient's ability
      to regulate diabetes. RESULTS: The proposed model offers a framework to
      demonstrate the complexity of diabetes management that may be unique to the
      African American experience. CONCLUSIONS: A comprehensive view of the
      environmental context will lead to new and more effective approaches in diabetes
      education and counseling for African American adults with type 2 diabetes.

PMID- 12212019
TI  - A national job analysis of certified diabetes educators by the National
      Certification Board for Diabetes Educators.
AB  - PURPOSE: The job analysis described in this report was conducted by the National
      Certification Board for Diabetes Educators (NCBDE) to (1) provide a basis for
      documenting the continuing validity of the certified diabetes educator
      examination (CDE), (2) define areas that should be assessed in future
      certification examinations, and (3) ensure that the content of certification
      examinations is job related. METHODS: A diabetes educator job task list was
      developed and used to create a job analysis survey. The survey was distributed
      randomly to 1079 CDEs throughout the United States. RESULTS: Of the 1079 surveys
      that were distributed, 327 were suitable for analysis, with relevant demographic
      subgroups adequately represented. An examination matrix and detailed content
      outline were constructed from the survey data that will be used by the NCBDE to
      assemble future test forms. CONCLUSIONS: Specifications for the CDE examination
      were developed that were directly related to the important activities that
      diabetes educators perform. Future forms of the CDE examination will be matched
      to job-related, criterion-referenced test specifications and will have strong
      evidence of content validity. Future forms of the exam will contain 200 items at
      specified cognitive levels with a representative sampling of tasks within 4 core
      areas from the detailed content outline.

PMID- 12212020
TI  - Peer coaching: an intervention for individuals struggling with diabetes.
AB  - PURPOSE: The purpose of this study was to determine the value of peer coaching
      and its influence on behavior change. METHODS: Coaches who were known to be
      successfully managing their diabetes were paired with individuals who were
      struggling with behavior change associated with managing diabetes. The pairs were
      matched according to age, sex, and physical appearance. Coaches met initially
      with participants in a face-to-face meeting for 1 hour and talked with them once
      a week for 10 to 15 minutes for the next 8 weeks. The initial interview and
      subsequent phone conversations focused on the person's problems and efforts at
      behavior change. RESULTS: At the end of the study, the pairs participated in a
      videotaped focus group to discuss their views on coaching and its influence on
      behavior change. Participants reported that coaching was personal, useful in
      disease management, and helpful in their quest to establish and adhere to
      routines of care. Participants also reported making progress toward changing
      their behavior related to diet, exercise, and blood glucose monitoring. Sustained
      behavior change was not measured. CONCLUSIONS: Peer coaching appears to have
      merit as a viable, low-cost intervention with the potential of helping
      individuals with diabetes who need to change their behavior.

PMID- 12212021
TI  - [Phamacognostical identification of medicinal plants of paederia].
AB  - OBJECTIVE: To distinguish accurately the dried medicinal plants of Paederia in
      Guangxi Province. METHOD: Using regular methods for identification of crude
      drugs. RESULTS: Obvious distinctions were found among leaf quality, presence of
      hair characteristics, inflorescence morphology, presence of non-glandular hair
      and scleroid cells along with their sizes, forms and superficial characteristics.
      Obvious distinctions were also found among cuticular veins of leaf cuticles,
      projecting of cells' outer walls, development of metaxylem, shapes and separation
      of crystal cells and wood fibers under microscope. CONCLUSION: All the above
      mentioned characteristics can be used for species identification.

PMID- 12212022
TI  - [Infrared spectral identification of rhizoma Corydalis and rhizoma Corydalis
      repentis].
AB  - OBJECTIVE: To study the IR spectra of Rhizoma Corydalis and Rhizoma Corydalis
      Repentis. METHOD: The petroleum ether, ethyl ether and water extracts obtained by
      the same isolating procedure from Rhizoma Corydalis and Rhizoma Corydalis
      Repentis were determined by IR spectrophotometry. RESULTS: The IR spectral
      evidences of the two samples showed distinct characteristics and good
      repeatability. CONCLUSION: The IR spectral evidences can be used to differentiate
      Rhizoma Corydalis and Rhizoma Corydalis Repentis.

PMID- 12212023
TI  - [Determination of chlorogenic acid in chrysanthemum morifolium Ramat.flower].
AB  - OBJECTIVE: To determine the contents of chlorogenic acid in flower of
      Chrysanthemum morifolium. METHOD: Column: Nova-Pak C18, 4 microns, 4.6 mm x 250
      mm, mobile phase: MeOH-0.1 mol.L-1 NaH2PO4(pH 2.65)30:70, detection wavelength:
      328 nm. RESULTS: Flowers of 20 batches bought from the market were analysed.
      Contents of chlorogenic acid were 0.060%-0.467%. CONCLUSION: Chlorogenic acid is
      a suitable component for the quality control of C. morifolium.

PMID- 12212024
TI  - [Effect of space flight on ultrastructure in medicinal plant Datura innoxia
      Mill].
AB  - OBJECTIVE: To substantiate the effect of space environment on medicinal plants.
      METHOD: The seeds of Datura innoxia were set up in retrievable satellites. After
      returning to earth, the ultrastructural changes were observed by means of
      electron microscope. RESULTS: In cells of weightless group and hit group, some
      changes were found in chloroplast grana, starch grains and vesicles in
      chloroplasts. No obvious changes were observed in nuclei. CONCLUSION: Space
      environment has some effect on the ultrastructure in D. innoxia, and chloroplast
      is more sensitive to space environment than other organs.

PMID- 12212025
TI  - [Morphological studies on seeds from 5 species of medicinal Rhododendron].
AB  - OBJECTIVE: To provide a scientific evidence for the identification of
      Rhododendron species. METHOD: Investigation of the seed form of 5 species of
      Rhododendron was done by electronic microscope scanning. RESULTS: R. simsii
      belongs to the wingless type, and R. augustinii, R. decorum, R. delavayi and R.
      discolor belong to the winged type. CONCLUSION: The 5 species of medicinal
      Rhododendron can be distinguished according to such features as the form, wing
      and rib of seeds.

PMID- 12212026
TI  - [Analysis of the genetic relationship among the three types of Trichosanthes
      kirilowii Maxim. by random amplified polymorphic DNA (RAPD)].
AB  - OBJECTIVE: Discussing the discordance in purchasing and utilizing a new type of
      Trichosanthes kirilowii called "Niuxin-gualou" from Shandong Province. METHOD:
      The genetic relationship among the three types of T. kirilowii including "Ren
      gualou", "Tang-gualou" and "Niuxin-gualou" from Shandong was analyzed by random
      amplified polymorphic DNA(RAPD). RESULTS: Among the three types studied, the
      genetic distance is the smallest between "Niuxin-gualou" and "Ren-gualou", and
      the largest between "Niuxin-gualou" and "Tang-gualou". CONCLUSION: "Niuxingualou"
      is genetically more similar to "Ren-gualou".

PMID- 12212027
TI  - [Studies on precipitate of Huanglian-Huangqin couples in decoction].
AB  - OBJECTIVE: Chemical composition of precipitate was researched when Huanglian
      Huangqin was decocted. METHOD: Ployamide column chromatography, TLC and TOF-MS
      were used. RESULT: The precipitate contains berberine, palmatine, jalrorrhizing,
      epiberberine, copticine, baicaling and wogonoside. CONCLUSION: The precipitate is
      effective composition in Chinese medical decoction. The research provides new
      data on medical effects of Huanglian-Huangqin couples.

PMID- 12212028
TI  - [Chemical constituents of Cynanchum chinense R. Br].
AB  - OBJECTIVE: To investigate the chemical constituents in the aerial part of
      Cynanchum chinense. METHOD: The chemical constituents were extracted with solvent
      and separated by column chromatography. The structures were identified by
      spectral methods: RESULT: The structures were identified as 7-O-alpha-L-rhamnopy
      ranosyl-kaempferol-3-O-alpha-L-rhamnopyranoside, 7-O-alpha-L-rhamnopy-ranosyl
      kaempferol-3-O-beta-D-glucopyranoside and 7-O-alpha-L-rhamnopyr-anosylkaempferol
      3-O-beta-D-glucopyranosyl(1-->2)- beta-D-glucopyranoside. CONCLUSION: All the
      three compounds were separated from C. chinense for the first time.

PMID- 12212029
TI  - [Determination of buddlejasaponin IV in Clinopodium Linn. by HPLC].
AB  - OBJECTIVE: To determine the contents of buddlejasaponin IV in Clinopodium plants.
      METHOD: A high-performance liquid chromatographic method was used to determine
      buddlejasaponin IV in Clinopodium plants and Tabellae Clinopodii. The
      determination was carried out on a C18 reversed-phase column by methanol
      water(70:30) elution solvent with UV detection at 210 nm. RESULT: The contents of
      buddlejasaponin IV in different samples were different. The average recovery was
      101.3% and RSD 1.73%. CONCLUSION: The method for determining buddlejasaponin IV
      was established for the first time.

PMID- 12212030
TI  - [Determination of stilbene in radix Polygoni multiflori by HPLC and its stability
      study].
AB  - OBJECTIVE: To develop a HPLC method for determining stilbene in Radix Polygoni
      Multiflori and studying its stability. METHOD: HPLC conditions: An Econosphere
      C18 column, a mixture of methanol-water(30:70) as mobile phase, and UV detection
      at 310 nm. In addition, the stability of stilbene was studied at high temperature
      and in acidic solution. RESULT: The linear range of calibration curve was 2.24 x
      10(-2)-1.12 x 10(-1) micrograms(n = 6) with a correlation coefficient of 0.99998,
      the average recovery with RSD being 99.96% +/- 1.54%. CONCLUSION: The method is
      sensitive, accurate and speedy. Stilbene in aqueous solution is stable, but high
      temperature(80 degrees C) tends to affect the stability. In acidic solution no
      stability can be found.

PMID- 12212031
TI  - [The effect of cold- and heat-natured medicines on 5-HT and NE cells and nerve
      fibres in rat's brain, pituitary and adrenal].
AB  - OBJECTIVE: To study how cold- and heat-natured medicines act on 5-HT and NE cells
      in the brain, pituitary and adrenal of rats. METHOD: Based on immunohistochemical
      method, the specific anti-TH and anti-5-HT sera were used to observe the changes
      of 5-HT and NE cells in brain and adrenal as well as fibres in pituitary. The
      contents of these two transmitters in brain were also determined by
      fluoriphotometry. RESULTS: Cold-natured medicines made the staining of 5-HT cells
      deeper and NE cells lighter, while heat-natured medicines act by contraries.
      CONCLUSION: Cold-natured medicines increase the content of 5-HT in brain and
      decrease the content of NE, while heat-natured medicines work the other way
      around. The morphologic changes are consistent with the functional ones.

PMID- 12212032
TI  - [Hepatoprotective effect of several constituents of Lonicera fulvotomentosa hsu
      et S. C. cheng, and L. macranthoide Hand.-Mazz. on CC1(4) and D-galactosamine
      induced liver injuries in mice and rats].
AB  - OBJECTIVE: To study the hepatoprotective effect of several constituents of
      Lonicera fulvotomentosa and L. macranthoide on CC1(4) and D-Galactosamine induced
      liver injury in mice and rats. METHOD: Mice and rats were given s.c. several
      constituents of L. fulvotomentosa and L. macranthoide, sGPT, hepatic
      triglycerides(TG) and malondialdehyde (MDA) were determined. RESULTS: All the
      compounds reduced the rise of sGPT and TG induced by CC1(4) and D-Galactosamine.
      Hepatic MDA formation caused by CC1(4) was also significantly decreased.
      CONCLUSION: Several constituents of L. fulvotomentosa and L. macranthoide are
      effective in decreasing CC1(4) and D-Galactosamine-induced liver injuries, and
      this effect appears to be due to the decrease of lipid peroxidation of CC1(4).

PMID- 12212033
TI  - [Effect of sodium ferulate on proliferation of rabbit aortic smooth muscle cells
      induced by oxidized LDL].
AB  - OBJECTIVE: To investigate the effect of sodium ferulate on the proliferation and
      lipid peroxidation of aortic smooth muscle cells(SMC). METHOD: Using experimental
      models of proliferation of cultured rabbit aortic SMC induced by oxidized-low
      density lipoprotein, the level of lipoperoxide(LPO) was determined by
      thiobarbituric acid reactive substance(TBARS) method and 3H-thymidine(3H-TdR)
      incorporation was used to observe DNA synthesis. RESULTS: SF markedly reduced the
      increase of medium LPO and inhibited the 3H-TdR incorporation in a dose-dependent
      manner. CONCLUSION: SF can inhibit the proliferation of SMC. The inhibitory
      effect may be related to the inhibition of lipid peroxidation.

PMID- 12212034
TI  - [The RYR1 genotype of the pigs from Neijiang of China].
AB  - The aim of this study was to test the RYR1 genotype of 25 Neijiang pigs ao as to
      provide data for the selective breeding of medical experimental pig strains. PCR
      RFLP technique was used. The results showed that the RYR1 genotype of all the 25
      porcine cases was HALNN and all of the 25 porcine cases were Halothane Negative.
      These suggested that Neijiang pig could be one of the porcine strains selectively
      bred for medical experiments and clinically for pig-to-human xenotransplantation.
      PCR-RFLP technique is a reliable and simple method for RYR1 gene testing.

PMID- 12212035
TI  - [Rapid determination of cefazolin in porcine serum by high performance capillary
      electrophoresis].
AB  - A rapid high performance capillary electrophoretic method was established to
      assay cefazolin in porcine blood serum. Porcine serum was deproteined by 60%
      acetonitrile and superlants were injected with 10 s pressure load. The final
      assay condition was: 40 cm x 75 microns silica capillary, 50 mmol/L bicarbonate
      buffer at pH10, 20 kV for 5 min, 254 nm UV detection. The assay was linear within
      the range of 5-320 micrograms/ml, the intra-day and inter-day relative standard
      deviations ranged from 1.7% to 8.0%. Analytical recovery of cefazolin was 107.9%,
      the limit of detection was 1.5 micrograms/ml, the limit of quantitation was 3.6
      micrograms/ml. To investigate the pharmacokinetic profile of cefazolin in pig,
      six adult pigs were injected with 16 mg/kg cefazolin and all data was analyzed by
      pharmacokinetic software 3P87. Cefazolin metabolism in adult pigs appeared to be
      a typical two-compartment model with a clearance of 8.43 ml/(kg.min).

PMID- 12212036
TI  - [A study on digestion of Gal alpha (1,3) Gal on porcine vascular endothelial
      cells by alpha-galactosidase].
AB  - This study was designed to explore ways to prevent immune rejection in
      xenotransplantation. Porcine vein endothelial cells treated by alpha
      Galactosidase were used to investigate the expression of Gal alpha(1,3) Gal on
      porcine vascular endothelial cells, and the morphology of vascular endothelial
      cells. The results showed that Gal alpha (1,3) Gal (alpha-Gal) on porcine
      vascular endothelial cells, which is the major epitome of xenoantigen, could be
      digested by alpha-Galactosidase within 30 minutes. No morphological changes were
      observed in the porcine vascular endothelial cells within a period of one hour
      after the treatment. This suggested that the treatment of porcine tissues with
      alpha-Galactosidase could be a new and effective way to prevent hyperacute
      rejection after xenotransplantation.

PMID- 12212038
TI  - [Immunogenicity and immunoprotection of a leptospiral DNA vaccine].
AB  - Leptospirosis is one of the most widespread zoonosis. Immunization of NZW rabbit
      with plasmid DNA constructs encoding leptospiral endoflagellin can induce
      specific antibody response in the animal. The vector, VR1012 consists of a pUC18
      backbone with the cytomegalovirus (CMV) IE1 enhancer, promoter, and intron A
      transcription regulatory elements and the BGH polyadenylation sequences driving
      the expression of leptospiral endoflagellar gene, flaB2. In this study, a pair of
      oligonucleotide primers were designed to amplify the endoflagellar of L.
      interrogans serovar lai. An approximately 840 bp fragment was generated with PCR
      and inserted into expressed plasmid vector, VR1012, after the fragment of VR1012
      were digested respectively with EcoRV and Sall. A recombinant plasmid (designated
      VR1012 + flaB2) was obtained. Plasmid encoding leptospiral endoflagellin was
      injected into quadriceps of NZW rabbits. This resulted in the generation of
      specific leptospiral antibody with very high ELISA titer. Immunoprotection was
      performed in guinea pigs. The group "VR1012 + flaB2" had higher survival rate,
      compared with the group "VR1012 only" (control) and the group "Normal Saline
      only" (control). The result suggests that the technique of DNA injection should
      have an advantage over certain previous vaccine technologies.

PMID- 12212037
TI  - [Immunohistochemical detection of hepatitis C virus antigen from hepatocellular
      carcinoma].
AB  - To investigate the infection of HCV and the expression of HCV antigen (HCAg) in
      HCC, immunohistochemical protocol was performed on tumorous liver tissues from 40
      patients with HCC to detect HCAg and hepatitis B virus surface antigen (HBsAg)
      simultaneously. The results showed that the positive rates for HCAg and HBsAg
      were 17.5% (7/40) and 70% (28/40) respectively. HBsAg and HCAg were
      simultaneously detected in six of 40 cases and only one case had HCAg positive
      alone in the liver tumorous tissue. The positive signals were localized in
      diffuse cytoplasm of hepatocytes and the positively stained cells were mainly
      distributed in local pattern. The results suggested that HCV infection did exist
      in some cases of HCC, so HCV might be a viral risk factor in addition to HBV in
      the genesis of HCC in China.

PMID- 12212039
TI  - [DNA typing for HLA-A by polymerase chain reaction with sequence-specific
      primers].
AB  - The authors have established a method of DNA typing for HLA-A antigen in Chinese
      by using polymerase chain reaction with sequence-specific primers (PCR-SSP). HLA
      A alleles were successfully typed in all clinical samples and 36 standard DNAs by
      PCR-SSP. A total of 635 A antigens were typed in 345 donor-recipients, including
      55 homozygotes and 290 heterozygotes. Twenty alleles of HLA-A were accurately
      distinguished by DNA typing. No false positive or false negative typing results
      were obtained. Reproducibility was 100%. The overall time of DNA typing was 5
      hours. The typing results were concordant with the results of UCLA Tissue Typing
      Lab. Comparative study of HLA-A typing was carried out using PCR-SSP and standard
      serology. The results showed that the discrepancy rate of serology was 9.0%,
      containing 13 individuals incorrectly interpreted by serology and 16 serological
      "blanks" turned out to be a definable alleles by PCR-SSP. In conclusion, DNA
      typing for HLA-A by PCR-SSP has proved to be a high-resolution, high-specificity,
      rapid and accurate technique, suitable for clinical application with a greater
      precision than serology.

PMID- 12212040
TI  - [Comparative study on livertaxis of lactosaminated human growth hormone and
      galactosyl-human growth hormone].
AB  - This study was conducted to compare the livertaxis of lactosaminated human growth
      hormone (hGH-L) with that of galactosyl human growth hormone (hGH-Gal), using
      radioactive tracer technique. hGH-L and hGH-Gal were first prepared. After hGH-L,
      hGH-Gal and hGH were labelled with 131I or 125I, the data on biodistribution in
      mice, imaging in rabbits and chicken were obtained. hGH-L and hGH-Gal had
      remarkable livertaxis and their percentages for uptake in liver were 68.83%
      74.65% and 68.18%-74% respectively, which were about two times as high as that of
      hGH. All of the hepatic bindings were receptor-mediated. But, the synthesizing of
      hGH-L was more easy-to-do, more mild in reaction conditions, and more economical
      of raw material as compared with the synthesizing of hGH-Gal. Therefore, hGH-L is
      a more potential receptor-mediated hepatic targeting secreting somatomedian drug
      for treating dwarfism.

PMID- 12212041
TI  - [S-phase arrest associated apoptosis leads to diversities of drug resistance and
      mutation rate in human breast cancer cells].
AB  - To find out different abilities of drug resistance and mutation rate and its
      fundamental mechanism among the human breast cancer cells, two variants, L-2 and
      Br-1, derived from a common parent cell line of MDA-MB-435, were assayed for
      sensitivity to PALA and determined for their mutation rate to drug resistance by
      clone formation and fluctuation analysis respectively. Further, by means of cell
      growth rate test, flow cytometry, measurement of DNA fragmentation and western
      blot, the relationship between drug resistance and mutation rate and cell cycle
      control and apoptosis was explored. The results showed that the mechanism of S
      phase arrest associated apoptosis created such a different ability of drug
      resistance and stability of genome in two cell lines with identical p53 mutation.

PMID- 12212042
TI  - [Study of mutagenesis of two procarcinogens in human amnion cells using a shuttle
      vector pWB1].
AB  - Using 2 x 10(-5) mol/ml beta-NF (beta-naphthoflavone) to induce FL cells to
      express cytochrome P450 isozymes at a reasonable level, we have studied the
      mutagenesis of two procarcinogens, aflatoxin B1 and benzo (alpha)pyrene, at four
      different doses. Except for their top doses, all other doses induced mutation in
      target gene SupF carried by plasmid pWB1 at the frequency of 10(-4), which is
      higher than the spontaneous mutation frequency (7.61 x 10(-6)). Aflatoxin B1
      demonstrated normal effect-dose relationship. Meanwhile no mutant was detected in
      their correspondent negative controls. All the results suggest that shuttle
      vector pWB1 can be conveniently used for detection of procarcinogens and study of
      their mutagenesis mechanisms in human cells.

PMID- 12212043
TI  - [Distribution of nitric oxide synthase-positive neurons in the hypothalamus of
      cat].
AB  - NADPH-diaphorase histochemistry was used to study the distribution of Nitric
      Oxide Synthase (NOS)-Positive neurons in the hypothalamus of adult cat. NOS
      positive neurons were observed in the paraventricular hypothalamic nucleus,
      suprachiasmatic nucleus, dorsomedial hypothalamic nucleus, perifornical nucleus,
      anterior hypothalamic area and lateral hypothalamic area. Two differences between
      the cat and rat were noticed. Firstly, NOS-positive neurons were observed in the
      suprachiasmatic nucleus of cat, but the neurons in that of rat were negative for
      NOS. Secondly, the neurons in supraoptic nucleus of rat exhibited an intensive
      reaction to NADPH-diaphorase, but those in that of cat were faintly visible.

PMID- 12212044
TI  - [Kinetics of the Ca(2+)-activated K+ channel in Ca2+ induced cortex neurons
      damage].
AB  - Ca(2+)-activated K+ channels were studied by using the patch clamp technique of
      single channel recordings from the primary culture fetal SD rat cortex neurons.
      Besides their physiologic characters, the effects of increasing cytosolic and
      cytoplasmic Ca2+ triggered neuronal damage were also studied. The results showed
      that Kca with conductance around 170PS was predominant in the rat cortex neurons.
      These channels almost did not open at physiologic intracellular free Ca2+
      concentration (10(-8) mol/L), but was extremely activated at intracellular free
      Ca2+ concentration (10(-6) mol/L). So the open probabilities of the KCa in the
      cortex neurons obviously depended on the concentration of cytoplasmic Ca2+ and
      membrane potential. The KCa activated by increasing of intracellular Ca2+ during
      the early stage of anoxia may be a protective reaction of ischemic neurons.

PMID- 12212045
TI  - [Effects of reperfusion on neuronal changes and macrophagic response after
      transient focal ischemia--reperfusion of brain in rats].
AB  - Male SD rats(n = 29) were subjected to 2 hours' middle cerebral artery occlusion
      and were killed at various times of reperfusion (0.5-48 hours). The histological
      features of neuronal changes, the macrophagic response and the relationship
      between them were investigated. The neurons underwent acute changes(shrinking or
      swollen), and the pyknotic apoptotic neurons were occasionally seen within 3
      hours. The number of apoptotic neurons increased with recirculation time. The
      scattered red neurons and ghost cells were first found at 6 hours of reperfusion.
      Many apoptotic neurons, apoptotic bodies were detected in the penumbra of
      ischemic core at 48 hours. Lectin histochemistry with GSI-B4 was performed to
      observe the macrophage. The results showed the active microglia and macrophage
      from meninges presented at 12 hours. The macrophages from parenchyma vessels
      appeared at 24 hours. Reactive microglia and extrinsic macrophage aggregated into
      the band of macrophage which phagocytized the apoptotic neurons. The results
      indicate that, firstly, it is important to prevent the neuronal apoptosis and
      reduce the volume of infarct in stroke patients; secondly, irreversible neuronal
      lesions simultaneously stimulate microglial activation and the presence of
      extrinsic macrophages from meninges was earlier than the appearance of the
      macrophages from parenchyma blood-monocytes. The authors also suggest that the
      data on the neuronal changes over time after ischemia and reperfusion be useful
      reference materials for selecting the most timely medication to treat cerebral
      infarction.

PMID- 12212046
TI  - [The expression of IGF-I, TGF beta and Fas-L in granulosa cells of ovarian
      follicle with relation to the onset of atresia in rats].
AB  - This study was designed to investigate the effects of IGF-I, TGF beta and Fas-L
      on the sustaining of granulosa cells of ovarian follicle and the modulation of
      apoptosis of those cells, and to understand the molecular mechanisms of ovarian
      follicle atresia. Paraffin-embedded sections of SD rat ovary were made. Both
      TUNEL method and PCNA immunohistochemistry were employed to recognize atretic and
      healthy follicles. The expression of IGF-I, TGF beta, Fas-L and their receptors
      was displayed by immunostaining. The results showed that most of the granulosa
      cells within the healthy preantral and antral follicles were PCNA(+). At the
      early stage of atretic antral follicle, more than 5 granulosa cells were labelled
      by TUNEL method, and some granulosa cells were PCNA(+). At the late stage of
      atretic antral follicle, were labelled by TUNEL method. The immunoreactive
      products of IGF-I, IGF-IR, TGF beta, TGF beta R, Fas and Fas-L could be seen in
      the granulosa cells of healthy antral follicles. But, Granulosa cells were only
      TGF beta, TGF beta R and Fas immunopositive in all atretic antral follicles. In
      conclusion, combination of TUNEL method and PCNA immunochemistry is of benefit
      for distinguishing atretic follicles from healthy follicles. IGF-I might play an
      important role in stimulating proliferation of the granulosa cells and sustaining
      them. The lower expression or disappearance of IGF-I in the antral follicle might
      cause the onset of atresia. TGF beta, Fas-L and Fas might mediate apoptosis of
      the granulosa cells in antral follicles, causing follicle atresia. But, their
      effects of mediation could be inhibited as IGF-I exists in the follicles.

PMID- 12212047
TI  - [Dose-related response of adenosine in hypoxic pulmonary hypertension in
      canines].
AB  - The vasodilator test is of critical importance in determining the reversibility
      of pulmonary hypertension and hence the indication of surgical treatments for
      cases of marginal pulmonary hypertension associated with left to right shunt.
      This study aimed at the dose-related vasodilation effect of adenosine (AD) on
      hypoxic pulmonary hypertension. The hemodynamic indexes were examined in 8
      canines with acute hypoxic pulmonary hypertension after administration of
      intravenous adenosine. The results showed that AD decreased both systemic and
      pulmonary pressures in a dose-dependent way, with very close linear correlation;
      so did the systemic and pulmonary resistance (r = -0.970 and -0.994,
      respectively; P < 0.001). The PASP reductions were significantly greater than
      SASP reductions at AD doses of 100 to 200 micrograms/(kg.min) (from -11.0% +/-
      4.2% to -27.7% +/- 14.8% vs from -2.6% +/- 7.4% to -14.9% +/- 7.0%,
      respectively), while PVR reductions were significantly greater than SVR
      reductions (-18.8% +/- 8.05% vs -10.2% +/- 6.86% and -29.8% +/- 14.46% vs -21.1%
      +/- 9.53%, respectively, P < 0.05). AD increased cardiac output and cardiac index
      to the significant degree only when the dosage increased to 300
      micrograms/(kg.min) or above. These results suggest that AD seems to be the
      choice of drug in vasodilator test of left to right shunt pulmonary hypertension,
      and the proper dosage ranges from 100 to 200 micrograms/(kg.min).

PMID- 12212048
TI  - [Effects of warm blood and clot crystalloid cardioplegia on the heart rate
      variability of canine].
AB  - The objectives of this study were to explore the mechanisms of cardiac autonomic
      system (CAS) impairment and to assess whether warm blood cardioplegia can prevent
      the decrease of heart rate variability (HRV) after CPB. Twelve adult mongrel dogs
      were divided into two groups. One group received warm blood cardioplegia and
      maintained at a systemic temperature of 38 degrees C throughout the experiment
      (WB group). The other received cold crystalloid cardioplegia at 31 degrees C and
      topical hypothermia (CC group). Anesthesia was induced and maintained with sodium
      pentobarbital and isoflurane. The heart was exposed through a right thorectomy.
      CPB was established using a single right atrial cannula. The arterial cannula was
      placed in the right femoral artery. The crossclamp time for both groups was 30
      minutes. Serum potassium levels were normalized throughout the study. Each
      animal's ECG was continuously recorded for 24 hours before surgery and for the
      first five postoperative days (POD) using a two-channel Holter monitor. The data
      were analyzed for heart rate variability (TP = total power, 0.01-1.00; LF = low
      frequency, 0.04-0.15; HF = high frequency, 0.15-0.40; LF/HF). There were no
      differences in the preoperative values. In both groups the TP, LF, and HF
      decreased, compared to control (P < 0.05), with CC group having significantly
      lower TP, LF and HF than the WB group (P < 0.05). The LF/HF did not change both
      between groups and between before- and after-CPB in each group (P > 0.05). The
      mean heart rate at 24 hours (MHR) increased in both groups, compared to control
      (P < 0.05), with CC group having a significantly higher MHR than WB group (P <
      0.05). The data suggest that CPB, with warm blood or cold crystalloid
      cardioplegia does not disturb the balance of CAS, but it causes the decrease of
      HRV, and warm blood cardioplegia can not prevent the impairment of HRV.

PMID- 12212049
TI  - [The in vitro release kinetics of Daunorubicin polybutylcyanoacrylate
      nanoparticles].
AB  - The in vitro release kinetics of Daunorubicin Polybutylcyanoacrylate
      Nanoparticles(DNR-PBCA-NP) was studied by dynamic dialysis system. The
      concentration of Daunorubicin was determined by spectrophotometry. The result
      showed the in vitro release kinetics of DNR-PBCA-NP could be well characterized
      by a biexponential equation. There were two phases in the process of drug
      release. The initial phase was a fast release phase (the burst effect). The
      second phase was a slow release phase.

PMID- 12212050
TI  - [Effects of yi qi tong mai oral liquid on acute myocardial ischemia in dogs].
AB  - The objective of this study was to assess the prophylactic and therapeutic
      effects of Yi Qi Tong Mai Oral Liquid (YQTMOL) on acute myocardial ischemia. The
      models of ischemia were made, in which the anterior coronary arteries of
      anesthetized dogs were ligated. Four groups of dogs were examined and compared.
      We determined the extent of their myocardial ischemia and infarction by means of
      epicardial mapping and N-BT staining. The results showed that in the treatment
      groups, the increase of sigma-ST was inhibited 30-180 minutes after the oral
      administration of YQTMOL(compared with control group, P < 0.01), and the sigma-ST
      was decreased (P < 0.05). Furthermore, in the group dosed with YQTMOL (10 g/kg),
      the ratios of "area of infarction/heart weight" and "area of infarction/ventricle
      weight" both decreased (compared with control group, P < 0.05). These findings
      indicated that YQTMOL reduced the area of myocardial ischemia and the degree of
      myocardial infarction in dogs, so it could be effective for the prevention and
      treatment of acute myocardial ischemia.

PMID- 12212051
TI  - [Significance of specific time constant and F-V curve configuration in evaluating
      small airway function for smokers].
AB  - To evaluate the clinical significance of the specific time constant (S tau) and F
      V curve configuration in testing small airway functions for smokers, routine
      ventilatory functions, S tau and F-V curve configuration were studied in 116
      passive and light, heavy active smokers. Routine ventilatory functions and F-V
      curve configuration were determined with routine method. S tau were calculated
      from S tau = 1/V. The results showed that the distribution of convex type rose
      with the degree of smoking, and the decrease of V50, V25 and elongation of S tau
      50, S tau 25 in convex type were just consistent with heavy smokers. The range of
      elongation of S tau 50 and S tau 25 was 120%-130% of predicted value in both
      heavy smokers and convex type. These showed there were slight disturbances in
      functions of small airways. Compared with COPD patients previously measured,
      their S tau 75, S tau 50, S tau 25 all prolongated to higher degree and meant
      both large and small airways were affected. Therefore, the convex type,
      elongation of S tau 50 and S tau 25, and decrease of V50 and V25 were sensitive
      indices for detecting small airway functions. They can be recommended for
      clinical application.

PMID- 12212052
TI  - [Microvessel count in normal cervical tissue and in cervical carcinomas].
AB  - This study was conducted to determine microvessel count(MVC) status in normal
      cervical tissue (NCT) and in cervical carcinomas (CCs). 15 cases of NCT and 80
      cases of CCs were stained by immunohistochemical method for Factor VIII related
      antigen (F8RA). The results showed that the MVC in CCs was much higher than that
      in NCT and it was correlated with clinical stage, size of tumor and lymph node
      status (P < 0.05). Every time when MVC increased by 5 in number (LM x 200, field
      0.739 mm2), the chance of lymph node metastasis increased by 1.61 times. There
      was no relationship between MVC and tumor grade. These suggested that MVC might
      be a useful early parameter in the diagnosis and prognosis of CCs.

PMID- 12212053
TI  - [The change of plasma level of endothelin-1 in patients with cor pulmonale and
      the effects of Captopril].
AB  - The purpose of this study was to investigate the role of endothelin(ET) in the
      development of cor pulmonale and the mechanism of captopril in treatment. The
      plasma ET-1 levels of 36 patients with cor pulmonale and 20 normal subjects were
      measured by radioimmunoassay. Twenty patients were treated with antibiotics and
      oxygen, and the other 16 patients were treated with antibiotics, oxygen and
      captopril for 14 days. The results showed that the ET-1 level of patients with
      cor pulmonale (88.9 +/- 8.9 ng/L) was significantly higher than that of normal
      control (53.5 +/- 5.1 ng/L). After treatment, the ET-1 level declined
      significantly in both groups of patients (P < 0.01); the ET-1 level in patients
      treated with captopril was lower than that in patients not treated with captopril
      (P < 0.05), but the level of ET-1 in patients was still higher than that of
      normal control (P < 0.05). These suggest that ET-1 may play an important role in
      the onset of cor pulmonale and captopril can reduce the ET-1 level.

PMID- 12212054
TI  - [A clinical study on systemic inflammatory response syndrome and multiple organ
      dysfunction syndrome in patients with abdominal surgical emergency].
AB  - In order to analyze the development from systemic inflammatory response
      syndrome(SIRS) to multiple organ dysfunction syndrome (MODS) and probe the
      therapeutic strategies, the authors studied retrospectively the clinical data of
      SIRS and MODS in 1374 patients with abdominal surgical emergency. The results
      showed that on admission the morbidity of SIRS was 32.5%, afterwards the
      morbidity of MODS was 6.4%, and the mortality of the patients with SIRS was 4.8%.
      After 48 hours' therapy, MODS developed in 33.0% of the SIRS cases. Of all the
      1374 patients, 40 developed MODS(2.9%) and 27 died (67.5%). The authors point out
      that the outcome of the patients with abdominal surgical emergency can be
      improved on condition that SIRS is early diagnosed, the cause of SIRS after 48
      hours of therapy is well defined, and the body inflammatory response is properly
      regulated.

PMID- 12212055
TI  - [Significance of apoptosis status and apoptosis-associated antigen expression in
      human colorectal adenocarcinoma sequence].
AB  - To investigate the effects of apoptosis on colorectal tumorigenesis and its
      possible biological significance, the apoptotic frequency in primary cultural
      cell of 9 normal mucosa, 4 adenomas and 9 adenocarcinomas in time period of 2,
      12, 24, 48 hour was measured by flow cytometry. The apoptotic cells index (AI) in
      situ for 15 colorectal normal mucosa, 7 hyperplastic epithelial, 25 adenomas and
      77 adenocarcinomas was identified by the terminal deoxynucleotidyl
      transferasemediated dUTP-biotin nick end labeling technique (TUNEL). Ki-67
      proliferate index (KI), wafl and p53 genes were immunostained with ABC method.
      The results showed that culture related apoptotic incidence was obviously
      decreased in cultural tumor cell when compared with mucosa cell after 24-48 hour
      in vitro. There was a directly positive relationship between the spontaneous
      apoptosis and Ki-67-index in vivo. The well differentiated or early stage lesions
      with intensive bcl-2 expression were significantly more likely to have low AI and
      KI. Both mp53 accumulation and wafl depression which mainly related to KI, had no
      apparent correlation with AI, bcl-2/bax expression and clinicopathological
      features statistically; elevatory bax/bcl-2 and pervasive wafl depression led to
      an increasing AI/KI both in adenoma with atypia and in advanced cancer with
      distant metastasis or embolus, comparatively. The data indicated that the
      reduction of susceptibility to inductive apoptosis may contribute to the early
      phase of tumorigenesis, that AI in vivo may reflect proliferative activity, and
      that bcl family was closely associated with spontaneous apoptosis and biological
      behavior of human colorectal cancer.

PMID- 12212056
TI  - [Pathological morphology of arterioles and main visceal organs in primary
      hypertension--an analysis of 45 autopsies].
AB  - The autopsy materials of 45 cases of primary hypertension were studied
      retrospectively. The arteriolar lesions were reviewed. The arterioles < 100
      microns in diameter were defined as distal arterioles; those > or = 100 microns
      and < 300 microns in diameter were proximal arterioles. The lesions of arteriolar
      wall were categorized as plasma infiltration and hyaline degeneration, and
      according to seriousness, the latter was divided into three degrees: I, II and
      III. The results revealed that (1) the arteriolar lesions in different areas of
      the body were at different stages of seriousness; (2) the changes in the distal
      arterioles were earlier than those in the proximal ones; in brain, the proximal
      arterioles dilated first, and then occurred the hyline degeneration; (3) hyaline
      degeneration took place early in the abdominal organs such as kidney, liver and
      pancreas, but relatively late in brain; (4) different parts of an organ were at
      different stages of seriousness; and (5) the lesions in different organs led to
      different consequences. The pathogenesis of arteriolar sclerosis in primary
      hypertension was also discussed.

PMID- 12212057
TI  - [Preliminary study on apoptosis and expression of apoptosis-related genes in
      peripheral blood lymphocytes of patients with systemic lupus erythematosus].
AB  - This study was conducted to explore the clinical implication of the relationship
      between systemic lupus erythematosus (SLE) and peripheral blood lymphocytes (PBL)
      apoptosis and apoptosis-related gene expression. Terminal deoxynucleotidyl
      transferase mediated nick end labelling technique and flow cytometry were used to
      detect the apoptotic cell; immunohistochemistry ABC was used to detect the
      expressions of bcl-2 and Fas in 29 cases of SLE. The results showed that the rate
      of apoptosis of PBL in SLE patients was significantly higher than that in normal
      control (P < 0.001), and that in patients with rheumatoid arthritis (P < 0.001).
      After 48 hour's culture, the apoptotic rate further increased in SLE patients
      (33.44%). There was a significant correlation between the SLE activity and the
      rate of apoptosis in vitro (r = 0.86, P < 0.001). The rate of apoptosis of PBL in
      SLE-nephritis patients was higher than that in non-SLE-nephritis patients (P <
      0.01). Before and after the culture, the expressions of bcl-2 and Fas in PBL of
      patients with SLE were higher than those in normal control (P < 0.01, P < 0.001).
      So the authors suggest that increased rate of apoptosis may be used as an index
      for evaluating the severity of SLE cases.

PMID- 12212058
TI  - [Changes and clinical significance of serum thyroxine level in patients with
      congestive heart failure].
AB  - In order to explore the relationship between congestive heart failure (CHF) and
      serum thyroxine, we assayed serum thyroxine level in 52 patients with CHF and 28
      normal persons by means of radioimmunoassay (RIA). The results showed that
      triiodothyronine reduced and reverse triiodothyronine elevated significantly in
      the patients compared with the normal (P < 0.05). The more severe heart failure
      developed, the more obvious changes of the hormones were observed. The results
      suggest that the alterations of serum thyroid level may be used as an index of
      the severity of heart failure.

PMID- 12212060
TI  - [A pair-matched comparison and follow-up study of patients with euthytroid Graves
      ophthalmopathy and patients with hyperthyroid graves ophthalmopathy].
AB  - This study was intended to acquire a knowledge about the similarity and
      difference between euthyriod Graves ophthalmopathy (EGO) and hyperthyroid Graves
      ophthalmopathy (HGO), and about the outcome of the EGO cases. Twenty-seven EGO
      patients were pair-matched with 27 HGO patients, and 18 of the EGO patients were
      followed up for 1-6 years. The results showed that the EGO group had markedly
      more patients with diplopia, failure to close lids, limitation of eyeball
      movements, cornea involvement, and more patients with a difference of two eyes'
      exophthalmos degrees > or = 2 mm, but the HGO group had more patients with optic
      nerve involvement. No significant difference was found between the two groups'
      ophthalmopathic indexes by using the t-test. Drug therapy of the EGO group was
      more efficacious than that of the HGO group. The results of follow-up study
      showed that 61% of the EGO cases had hyperthyroidism and goiter within 5 months
      to 3 years, but 39% of the cases had no hyperthyroidism up to 6 years. These data
      suggest that EGO is associated with thyroid diseases and it can stand "alone" as
      an auto-immune disease.

PMID- 12212059
TI  - [Effect of arginine on deep partial-thickness burn in rats].
AB  - To investigate the therapeutic effect of arginine on burn, a randomized
      controlled trial in 20% TBSA deep partial-thickness burned rats was designed. The
      rats' wound healing, cellular immunity and nitrogen balance were evaluated at
      appointed postburn days. The results showed that the arginine group got better
      wound healing and faster recovery of cellular immunity, and achieved positive
      nitrogen balance. These suggest that supplement of exogenous arginine after burn
      may be beneficial to the victim in promoting would healing, reducing postburn
      immune suppression and enhancing anabolism of protein.

PMID- 12212061
TI  - [Effects of Dexamethasone, Fluorometholone and Florex on intraocular pressure
      after photorefractive keratectomy].
AB  - To evaluate the results of elevated intraocular pressure (IO) secondary to
      dropping of 0.1% Dexamethasone, Fluorometholone and Florex for 1-3 months after
      photorefractive keratectomy, we summed up and analysed the 3-month follow-up data
      on 546 eyes in three groups. The rates of IO elevated in Dexamethasone,
      Fluorometholone and Florex were 36%, 12.4% and 31.9% respectively. After topical
      use of corticosteroid, some of the elevations of IO took place as early as two
      weeks, but most of them occurred around 1 month. Eleven patients with IO
      elevation of both eyes had visual acuity decreased associated with eye-ache and
      halos and the other patients had no symptoms. After discontinuation of
      corticosteroid and institution of antiglaucoma therapy, the IO became normal in 3
      7 days. In practice, this means that patients receiving corticosteroid eyedrops
      for more than two weeks should be checked for the possibility of ocular
      hypertension to prevent the corticosteroid glaucoma.

PMID- 12212062
TI  - [Sonographic measurement of uterine cervix in pregnancy].
AB  - The objective of this study was to evaluate the accuracy of the measurement of
      the cervix by comparing transvaginal sonography (TVS) with transabdominal
      sonography (TAS) and to assess TVS measurement of the cervix in pregnancy. The
      cervix was measured in the first, second, third trimesters and at term by TVS in
      131 normal singleton pregnancies and by TAS in normal pregnant women. The results
      showed that TVS was better in providing successful rate and accurate
      identification of uterine cervical length, compared with TAS. The cervical
      lengths in the first, second, third trimesters and at term were 30.22 mm, 32.25
      mm, 30.04 mm and 25.86 mm respectively. The results suggest that TVS be superior
      to TAS in cervical measurement and that in normal pregnancy, the cervical length
      does not change significantly until the time when cervical length shortening
      begins at term.

PMID- 12212063
TI  - [The maternal-fetal harm study of intrahepatic cholestasis of pregnancy].
AB  - The aim of this study was to assess the harm of intrahepatic cholestasis of
      pregnancy (ICP) to the mother and fetus. The symptoms, liver function and outcome
      of 471 cases of ICP in our hospital during 1989-1996 were studied
      retrospectively. The mean pregnant weeks when pruritus first came on was 32.4 +/-
      4.7 (12-40) weeks, the incidence of preterm delivery 16.6% (78 cases); the
      perinatal mortality 12.7@1000 (6 cases). The incidence of the cases associated
      with amnion fluid II degree-III degree (n = 108) was 24.2%. The relationship
      between the mode of delivery (natural labor = 1, forceps delivery = 2, cesarean
      section = 3) and newborn Apgar scores was positive (r = 0.1188, P < 0.05). The
      amniotic fluid status in the group of 30-33(+6) pregnant weeks was significantly
      worse than that in the group of term pregnancy (0.89 +/- 1.11 vs 0.55 +/- 0.96, P
      < 0.05). The amniotic fluid status in the group with serum total bilirubin > 34
      mumol/L was worse than that in the 17.1-34 mumol/L group (0.96 +/- 1.1 vs 0.65 +/
      1.04, P < 0.05), and that in the group with serum total bile acid concentration
      > 40 mumol/L was worse than that in the serum total bile acid normal group (< or
      = 20 mumol/L) (0.89 +/- 1.1 vs 0.33 +/- 0.8, P < 0.05). Our results suggest that
      the severity of ICP may be indicated by early onset of pruritus (30-36(+6)
      pregnant weeks), the rising of serum total bilirubin level and the increasing of
      total bile acid concentration, and based on these indicators, timely cesarean
      section may increase the newborn Apgar scores.

PMID- 12212064
TI  - [Study on the radioligand binding assay of cholecystokinin receptor in rat
      cerebral cortex].
AB  - A radioligand binding assay system for determining the characterization of CCK
      receptor is presented. Using Bolton-Hunter reagent, we prepared a biologically
      active, specific 125I-BH-CCK8. The iodination mixture was then transferred to a
      column of Sephadex G-25 and examined by silica thin layer chromatography. Its
      specific activity and radiochemical purity were 3.4 TBq/mmol and 96%
      respectively. Binding of 125I-BH-CCK8 to the membrane of rat cerebral cortex was
      rapid, reversible, time-temperature dependent, saturable and specific. The
      labeled CCK was shown to have biological activity as measured by the CCK receptor
      radioassay. Under our laboratorial conditions, the CCK binding required an hour
      to reach equilibrium at 4 degrees C. We chose polyethylene glycol 6,000 and gamma
      globulin protein for the separation of B and F. Scatchard plot of CCK binding was
      linear with a Kd value of 1.098 nmol/L and Bmax of 197.5 fmol/mg protein. The
      results of this study support the stand-point that CCK may function as a
      regulatory peptide in brain and hence may be of use for clarifying the CCK
      receptor's function in central nervous system.

PMID- 12212065
TI  - [Application of enzyme-linked immunosorbent assay for cholecystokinin].
AB  - An enzyme-linked immunosorbent assay for octapeptide cholecystokinin (CCK) has
      been developed. Using this method we distinguished two kinds of CCK-related
      peptides and is also useful for identified the compounds with CCK-like structure
      in tissue extracts, as well as different antipeptide antisera. The results showed
      that this method could be applied to preliminary structure analysis of CCK.

PMID- 12212066
TI  - [Establishment of a heterologous graft model for human breast infiltrating duct
      carcinoma in nude mice].
AB  - A heterologous graft model for human breast infiltrating duct carcinoma is
      reported in this paper. The grafts derived from an infiltration duct carcinoma of
      a patient's right breast and her metastatic lymphnode mass were transplanted into
      the breast pads of nude mice in 1996, and the carcinoma masses were found in
      breast pads 31 days later. By now, the grafts of carcinoma have been transplanted
      into nude mice for 15 passages with a full success in 59 mice and with the
      biological characteristics of the original breast carcinoma. This heterologous
      graft model was established for the first time in China and the results suggest
      it be a good model for further research of breast carcinoma.

PMID- 12212067
TI  - [Determination of nitrite in serum and tissue by oscillopolarography].
AB  - A method for determining nitrite in serum and placenta tissue by
      oscillopolaropgraphy is reported in this paper. Nitrite in 0.10 ml of serum or
      placenta homogenate reacts with sulfanilmide and N-1 (1-Naphthyl)
      ethylendiamindihydrochloride in diluted hydrochloric acid medium to form an azo
      compound which can produce a sensitive reductive polarographic wave in ammonium
      alkaline medium. The wave height is directly proportional to the nitrite content,
      the method has a detection limit of 0.56 microgram/L (corresponding to the
      nitrite content of 0.61 mumol/L in serum or 0.22 microgram/g), RSD, of 6.1%-7.8%
      and recoveries of 92.0%-108.0% (mean value 100.6%). The method is sensitive,
      simple and can determine the nitrite directly without removal of the proteins in
      the samples.

PMID- 12212068
TI  - [Studies on chemical constituents of Stelmatocrypton khasianum (Benth.) H. Bail].
AB  - OBJECTIVE: To study the chemical constituents of Stelmatocrypton khasinum.
      METHOD: Using chromatographic methods to isolate compounds from S. khasinum and
      chemical and spectral methods to elucidate their structures. RESULT: Eight
      compounds, cleomiscosin A(1), 4-methoxy salicylicaldehyde(2), vanillin(3),
      isovanillin(4), 4-methoxy salicylic acid(5), isovanillic acid(6), 2,4-dihydroxy
      benzoic acid(7) and 4-hydroxy-benzoic acid(8) were isolated from the stem of S.
      khasianum. CONCLUSION: Except compound 2, all the compounds were obtained from
      this plant for the first time.

PMID- 12212069
TI  - [Studies on chemical constituents from the flower of Albizzia julibrissin
      Durazz].
AB  - OBJECTIVE: To study the chemical constituents in the flower of Albizzia
      julibrissin. METHOD: Chromatographic and spectroscopic analyses were used to
      isolate and elucidate the chemical constituents in the plant. RESULT: Two
      compounds were isolated from the petroleum ether and ethyl acetate fractions of
      the flower and identified as tetracosanoic acid and quercitrin. CONCLUSION: These
      two compounds were obtained from the plant for the first time.

PMID- 12212070
TI  - [Preventive effect of cardiomyopeptidin on rat heart injured by ischemia
      reperfusion].
AB  - OBJECTIVE: To investigate the preventive effect of cardiomyopeptidin of small
      molecular weight polypeptide on rat hearts injured by ischemia-reperfusion.
      METHODS: In a rat model injured by ischemia-reperfusion in the heart, observation
      was made on the influence of cardiomyopeptidin on the activities of creatine
      kinase (CK) and lactate dehydrogenase(LDH), as well as on the content of MDA in
      plasma after the preventive drug was used. RESULTS: Cardiomyopeptidin could
      obviously prevent the injury caused by ischemia-reperfusion, reduce the
      activities of CK and LDH and the content of MDA in a dose-dependent manner.
      CONCLUSION: Cardiomyopeptidin has a preventive effect on myocardium injured by
      ischemia-reperfusion and this may be related to its reducing the release of
      myocardial enzyme and anti-lipoperoxidation.

PMID- 12212071
TI  - [Studies on antitussive, antiasthmatic, expectorant and anti-inflammatory effects
      of Jin'an kechuan granules].
AB  - OBJECTIVE: To study the pharmacologic effect of Jin'an Kechuan granules. METHOD:
      Routine antitussive, antiasthmatic and expectorant methods were used. RESULT:
      Jin'an Kechuan granules in the doses of 16, 8, 4 g.kg-1 ig could significantly
      decrease the frequency of cough caused by ammonia water in mice, and increase the
      secretion of phenol red from mouse tracheas in a dose-dependent manner. The
      granules also help increase the threshold voltage to induce cats to cough,
      prolong the latent period of asthma induced by histamine and acetylcholine
      mixture, and antagonize the contraction of isolated trachea strips induced by
      histamine and acetylcholine in guinea pigs. Jin'an Kechuan granules had
      inhibitory effects on common bacteria in the respiratory tract as well as on the
      swelling of acute inflammation in mice and rats. CONCLUSION: Jin'an Kechuan
      granules have antitussive, antiasthmatic, expectorant and anti-inflammatory,
      antibacterial effects.

PMID- 12212073
TI  - [Chemical approaches to the research & development of modern traditional Chinese
      pharmacy].
AB  - OBJECTIVE: To study chemical approaches to the research and development of modern
      traditional chinese pharmacy. METHOD: To put forward several views on the aspects
      that concerns chemical approaches to the research and development of modern
      traditional chinese pharmacy. RESULT AND CONCLUSION: Dactyloscopic system should
      be set up for the quality control of traditional chinese medicinal materials and
      preparations. In the research of effective components in traditional chinese
      medicines proper treatment should be given to the new compounds that arise in the
      process of decocting compound prescriptions.

PMID- 12212072
TI  - [Experimental study on effect of sanmiao mixture capsules on prostate hyperplasia
      in mice and rats].
AB  - OBJECTIVE: To observe the effect of Sanmiao Mixture Capsules(SMC) on prostate
      hyperplasia in mice and rats. METHOD: The model of prostate hyperplasia was made
      by injecting testosterone propionate in to male mice(5 g.kg-1.d-1, 21 d) and
      rats(3 g.kg-1.d-1, 14 d). The treated group was administered SMC(mice: 36.3 g.kg
      1 and 18.2 g.kg-1; rats: 25.2 g.kg-1 and 12.6 g.kg-1), the normal control group
      1.9 g.kg-1, and the model control group NS. hours after the last administration
      serum tests were carried out on E2, AKP and Zn2+. Then the animals were killed,
      prostates taken out and weighed, index of prostate was calculated and
      pathological examination performed. RESULT: In the SMC treated group, the
      prostate weight and index were lowered(P < 0.01) the mean activation of E2 was
      raised, and the mean concentration of AKP and Zn2+ was inhibited (P < 0.01).
      CONCLUSION: SMC are helpful in checking prostate hyperplasia in mice and rats,
      the mechanism being probably related to the raising of activation of E2 as well
      as to the inhibition of concentration of AKP and Zn2+.

PMID- 12212074
TI  - [Agrobacterium-mediated medicinal plant transformation].

PMID- 12212075
TI  - [A study on quality standard of Rabdosia lophanthoides (Buch.-Ham. ex D. Don
      Hara)].
AB  - OBJECTIVE: To establish quality standards for safe and correct use of Rabdosia
      lophanthoides. METHOD: Field investigation and pharmacognostic study. RESULT: R.
      lophanthoides was confirmed as a derivative of R. lophanthoides. CONCLUSION: A
      convenient and effective method for identifying the herb has been established.

PMID- 12212076
TI  - [Establishment of symbiotic system for Anoectochilus roxburghii (Wall.) Lindl.
      and endophytic fungi].
AB  - OBJECTIVE: Setting up a symbiotic system for Anoectochilus roxburghii and
      endophytic fungi, so as to study the relationship between them and try to set up
      new cultural methods for A. roxburghii. METHOD: A. roxburghii and its endophytic
      fungi were cultured together on five kinds of media in flasks. The growth of the
      plantlets and fungi were observed. Symbiotic conditions were selected according
      to symbiotic characteristics. RESULTS: A symbiotic system for A. roxburghii and
      endophytic fungi was set up. The optimum composition of the system induded NH4NO3
      825 mg.L-1, KNO3 950 mg.L-1, MgSO4 185 mg.L-1, and inositol 100 mg.L-1, other
      organic components being 2/3 times those of MS medium, sugrose 15 g.L-1, and
      other components being the same as those of MS medium, agar 9 g.L-1, pH 5.8. The
      culture was effected at 24-25 degrees C under cool white fluorescent light (150
      lx) for a photoperiod of 11 hours. CONCLUSION: A. roxburghii and endophytic fungi
      can grow well together and form endomycorrhiza in the symbiotic system. Moreover,
      endophytic fungi help stimulate the growth and development of A. roxburghii.

PMID- 12212078
TI  - [Stable life prediction for a complex injection of Chinese materia medica by
      initial average rate stability test].
AB  - OBJECTIVE: To predict the stable life for a complex injection of Chinese materia
      medica. METHOD: The prediction was carried out by initial average rate stability
      tests, and the contents of puerarin and danshensu (major active components of the
      injection) were assayed by HPLC. RESULT: The degradation of puerarin followed the
      first order action, while danshensu was hard to determine; the t0.9,25 degrees C
      was 3.49 years and 1.69 years respectively. CONCLUSION: The stable life of the
      injection has been determined as 1.5 years.

PMID- 12212077
TI  - [Investigation on growth and development of Tussilago farfara L. in Beijing].
AB  - OBJECTIVE: To provide a scientific basis for the introduction and harvest of T.
      farfara in Beijing. METHOD: Random sampling in late growing period. RESULT: T.
      farfara reached the peak of vegetation growth in early September and concurrently
      began its reproductive growth. During this period its bud and rhizome began to
      form and develop and kept growing until the period of freezing weather.
      CONCLUSION: There are two optimum the times for reaping T. farara bud: one is
      around the fifteenth day before the period of freezing weather, and the other is
      around the tenth day after the thawing season in the next year.

PMID- 12212079
TI  - [The structure identification of Julibroside J6 from Albizia julibrissin Durazz].
AB  - OBJECTIVE: To study the saponin from Albizia julibrissin. METHODS: A saponin was
      separated by using chromatography and its structure was elucidated on the basis
      of spectral data. RESULTS: A saponin was obtained and it's structure was
      identified as 3-O-[beta-D-xylopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->6)
      beta- D-2-deoxy-2-acetamidoglucopyranosyl]-21-O-(6S-2-trans-2-hydroxymethyl- 6
      methyl-6-O-[4-O-(6S-2-trans-2-hydroxymethyl-6-methyl-6-hydroxy-2, 7-octadienoyl)
      beta-D-quinovopyranosyl]-2, 7-octadienoyl)-acacic acid-28-O-beta-D
      glucopyranosyl(1-->3)-[alpha-L-arabinofuranosyl- (1-->4)]-alpha-L-rhamnopyranosyl
      (1-->2)-beta-D-glucopyranosyl ester. CONCLUSION: The saponin is a new compound
      named Julibroside J6.

PMID- 12212080
TI  - [Determination of baicalin in banxiaxiexintang decoction different combinations
      of the by PR-HPLC].
AB  - OBJECTIVE: To the amount of baicalin in Banxiaxiexintang Decocted of different
      combinations were determined by PR-HPLC. METHOD: An YWG C18 column was used with
      a mobile phase of MeOH-H2O-H3PO4(47:53:0.05) and an UV detector at the wavelength
      of 274 nm. RESULT AND CONCLUSION: The amount of baicalin decreases when Radix
      Scutellariae is decocted with Rhizoma Coptidis, Rhizoma Pinelliae and Rhizoma
      Zingiberis.

PMID- 12212081
TI  - [Histological studies on rinds of 18 species of Gualou].
AB  - OBJECTIVE: To make clear the histological characteristics of rinds for eighteen
      species of Gualou. METHOD: Observing the cross sections and separate divide of
      the rinds with light microscope. RESULT AND CONCLUSION: Of eighteen rinds of
      Gualou, each trichome on exocarp, wood fiber and thickness of ring of stone cell
      are different from one another, this distinction can be used to identify the
      different rinds of Gualou.

PMID- 12212082
TI  - [Studies on quality standard of Fructus Amomi].
AB  - OBJECTIVE: To study the quality standard of different parts and species of
      Fructus Amomi from different producing. METHOD: GC method, ash determination and
      water determination. RESULT: The contents of bornyl acetate in different parts
      and species of Fructus Amomi from different producing areas were obviously
      different, but the traditional curative effects remained unchanged. The standards
      for the total ash content, acid-insoluble ash content and water content in
      Fructus Amomi have been set up. CONCLUSION: Bornyl acetate with a definite
      content limit should be chosen as the index in studying the quality standard of
      Fructus Amomi.

PMID- 12212083
TI  - [A study on fresh rhizome simulation model and its application to comprehensive
      agronomic measures for good quality and high yield of Curcuma longa L].
AB  - OBJECTIVE: To work out standardized cultivating measures for Curcuma longa
      according to the analysis of fresh rhizome simulation model. METHOD: Second order
      orthogonal rotative regression design. RESULT: The fresh rhizome simulation model
      was built up, and 5 main measures that affect fresh rhizome yield were analyzed
      by the mathematical model of five unknowns second order orthogonal rotative
      regression. Sowing time, plant population and potassium play an important role in
      raising the fresh rhizome yield. Sowing time is clearly interrelated with plant
      population, and plant population is clearly interrelated with the fertilizer used
      Sufficient N and K are necessary for raising the yield. There is a clear
      interrelation among the fertilizer factors. CONCLUSION: Optimal farming measures:
      sowing time March 1-17, and plant population-110,000 to 115,000 mother rhizomes
      per hm2. The optimal fertilizer requirements have also been formulated.

PMID- 12212084
TI  - [Studies on introducing and cultivating ginseng in Emei Mountain area].
AB  - OBJECTIVE: To introduce and cultivate Panax ginseng in Emei Mountainarea of low
      latitudes. METHODS: Introduce and cultivate ginseng in some fields of different
      elevations, and determine the contents of ginsenosides in ginseng samples
      obtained from the different elevations and different growth periods. RESULTS:
      Ginseng was successfully introduced to Emei Mountain area. Its quality basically
      approaches the quality of ginseng growing in northeast China. CONCLUSION: It is
      feasible to introduce and cultivate ginseng in Emei Mountain area with elevations
      from 1200 m to 1600 m.

PMID- 12212085
TI  - [A study on hemostatic and immunological actions of fresh and dry Dihuang].
AB  - OBJECTIVE: To investigate the difference between fresh and dry Dihuang (Radix
      Rehmanniae) in hemostatic and immunological actions. METHODS: The hemostatic
      action was assessed in aspirin-treated mice; immunological action was assessed by
      phagocytosis of macrophages in dexamethasone-treated mice; and Con A-induced
      mitogenesis and LPS-induced alkaline phosphatase activity of splenocytes were
      determined in thyroxin-treated mice. RESULT: The blood clotting in mice induced
      by aspirin was inhibited by oral administrations of juice decoction of fresh
      Dihuang or decoction of dry Dihuang alike. The action of fresh Dihuang juice was
      stronger than that of dry Dihuang decoction. Oral administrarion of fresh Dihuang
      juice or decoction for 10 days enhanced LPS-induced alkaline phosphatase activity
      of splenocytes in thyroxin-treated mice. The juice also enhanced Con A-induced
      splenocyte mitogenesis. The action of dry Dihuang decoction was weaker than that
      of fresh juice in increasing LPS-induced alkaline phosphatase activity.
      CONCLUSION: It is recommended to follow the tradition of using fresh Dihuang
      juice or decoction to treat some diseases such as hemorrhagenic troubles.

PMID- 12212086
TI  - [GC-MS analysis of essential oils from the roots of Saposhnikovia divaricata
      (Turcz.) Schischk, Libanotis laticalycina Shan et Sheh, Seseli yunnanense Franch.
      and Peucedanum dielsianum Fedde ex Wolff].
AB  - OBJECTIVE: To analyze the constituents of the essential oils from the roots of
      Saposhnikovia divaricata, Libanotis laticalycina, Seseli yunnanense and
      Peucedanum dielsianum. METHOD: GC-MS method was used. RESULT: 58 compounds were
      identified. CONCLUSION: To compare the constituents and their contents of 6
      samples, 3 samples of S. divaricata growing in 3 places are similar, L.
      laticalycina, S. yunnanense and P. dielsianum are different from S. divaricata in
      varying degrees.

PMID- 12212087
TI  - [Studies on chemical constituents of the roots of Gypsophila oldhamiana Miq].
AB  - OBJECTIVE: To separate compounds from the root of Gypsophila oldhamiana. METHOD:
      Chemical and chromatographic methods were used to separate the compounds. IR, MS,
      NMR were used to determine the structures of compounds. RESULT: Compound
      pentacosanoic acid, lacceroic acid, beta-sitosterol, alpha-spinasterol,
      daucosterol and sucrose were identified. CONCLUSION: All the above compounds were
      obtained from this genus for the first time.

PMID- 12212088
TI  - [Determination of flavonoids in pollen typhae(Puhuang) by HPCE and HPLC].
AB  - OBJECTIVE: To determine two flavonoids isorhamnetin-3-O-neohesperidoside(I) and
      typheneoside(II) in Pollen Typhae by HPCE and HPLC. METHOD: HPCE conditions:
      buffer = 0.02 mol.L-1 borate, 0.05 mol.L-1 SDS and 10% acetonitrile; V = 20 kV; T
      = 30 degrees C; lambda = 270 nm; sample size = 30 kPa.s, HPLC conditions: C18
      lumn, acetonitrile-water (15:85) as mobile phase detection wavelength at 254 nm.
      RESULT: The contents of flavonoids I and II in five different Typha species and
      eighteen commercial samples of traditional Chinese drug Puhuang were between 0.1%
      0.6%. CONCLUSION: These two methods are rapid, simple, accurate and can be used
      for the quality control of this traditional Chinese drug.

PMID- 12212089
TI  - [Quantitative determination of cholic acid in Calulus Bovis].
AB  - OBJECTIVE: To establish a method to determine the Content of cholic acid in
      Calulus Bovis. METHOD: The content was determined by TLCS. RESULT: Recovery rate
      was 96.54%, RSD was 1.68%. CONCLUSION: Accurate and reproducible, this method can
      be used for the quality control of Calulus Bovis.

PMID- 12212090
TI  - [Effect of feishuling on production of tumor necrosis factor alpha from hamster
      alveolar macrophages].
AB  - OBJECTIVE: To observe the effect of the traditional Chinese medicine Feishuling
      on the production of tumor necrosis factor alpha (TNF-alpha) from hamster
      alveolar macrophages in vitro and investigate the mechanism of its preventive and
      therapeutic effect on chronic obstructive pulmonary diseases(COPD). METHOD:
      Alveolar macrophages were harvested through bronchoalveolar lavage and cultured,
      Feishuling were added to the culture medium with lipopolysaccharide(LPS)
      simultaneously or 6 h after LPS. TNF-alpha production in the culture supernatants
      was tested by ELISA assay and the expression of TNF-alpha mRNA in the cells was
      measured through in situ hybridization. RESULT: After administration of
      Feishuling, the content of TNF-alpha in the supernatants and the expression of
      TNF-alpha mRNA in the cells were decreased more significantly than those in LPS
      stimulation group(P < 0.01), and there was a dose-effect relationship, but no
      significant differences were observed as compared with the simple culture medium
      group(P > 0.05). CONCLUSION: The effect of reducing the production of TNF-alpha
      from alveolar macrophages and inhibiting the damage mediated by TNF-alpha might
      be a part of the mechanism of Feishuling to prevent and treat COPD.

PMID- 12212091
TI  - [A study on nasal absorption of psoralen and isopsoralen in Psoralea corylifolia
      L].
AB  - OBJECTIVE: To investigate the nasal absorption regularities of psoralen and
      isopsoralen of different concentrations. METHOD: Building an experimental model
      of rat in situ nasal recirculation and determining the contents of psoralen and
      isopsoralen by HPLC. RESULT: The nasal absorption of psoralen and isopsoralen
      fitted in with zero order kinetics, getting saturated with the increase of
      concentration. CONCLUSION: A suitable concentration is necessary for the
      preparation of nasal remedies psoralen and isopsoralen.

PMID- 12212092
TI  - [Studies on immunomodulatory function of polysaccharide of Fructus Ligustri
      Lucidi].
AB  - OBJECTIVE: To explore the immunomodulatory mechanism of Chinese medicine Fructus
      Ligustri Lucidi and to find its efficient material base. METHOD: The effects of
      FLLPS on the immunoactivity of mouse speen lymphocyte were studied in vitro or
      vivo by means of MTT. RESULT: FLLPS could obviously promote the speen lymphocyte
      proliferation in normal mice and mice with Yin-deficiency selected by injection
      with adrenocorticortropic hormone. CONCLUSION: FLLPS has an immunomodulatory
      function for both normal mice and mice with Yin-deficiency.

PMID- 12212093
TI  - [Influence of drug compatibility on extractive retes of chlorogenic acid and
      isochlorogenic acid in simiaoyonglan tang decoction].
AB  - OBJECTIVE: To study the influence of drug compatibility on the extractive rates
      of chlorogenic acid and isochlorogenic acid in Simiaoyonglan Tang (SMYAT)
      decoction. METHOD: The contents of chlorogenic acid and isochlorogenic acid in
      SMYAT decoction, Flos Lonicerae and Flos Lonicerae in combination with other
      single drugs were determined by TLC-UV spectrophotometry respectively. The data
      from this experiment were treated statistically. RESULTS: The contents of
      chlorogenic acid in other five prescriptions of different compatibilities
      decreased markedly in comparison with those in Flos Loniceraes decoction (P <
      0.01). The content of isochlorogenic acid in SMYAT decoction as a whole was about
      the same as thar in Flos Loniceraes decoction, but decreased significantly in
      other prescriptions of different compatibilities (P < 0.01). CONCLUSION: Drug
      compatibility is one of the main causes for changes of chlorogenic acid and
      isochlorogenic acid contents in SMYAT decoction.

PMID- 12212094
TI  - [Studies on quality standards for Pollen Typhae(puhuang)].
AB  - OBJECTIVE: To work out quality standards for Pollen Typhae(Puhuang). METHOD:
      Isorhamnetin-3-O-neohesperidoside, typhaneoside, isorhamnetin and beta-sitosterol
      in Pollen Typhae marketed in ten cities of China were identified by TLC. The
      contents of isorhamnetin-3-O-neohesperidoside and typhaneoside were determined by
      HPLC. RESULT: The method is sensitive and specific for identifying isorhamnetin-3
      O-neohesperidoside, typhaneoside, isorhamnetin and beta-sitosterol. The linear
      ranges of isorhamnetin-3-O-neohesperidoside and typhaneoside were 0.188-0.940
      microgram with and average recovery of 97.77%; and 0.164-0.820 microgram with an
      average recovery of 98.42% respectively. CONCLUSION: The method can be used both
      qualitatively and quantitatively as standards for the quality control of Pollen
      Typhae.

PMID- 12212095
TI  - [A study on cultivation techniques for Glycyrrhiza uralensis fisch. in Daxing
      County area, Beijing].
AB  - OBJECTIVE: To study the suitable cultivation techniques for Glycyrrhiza uralensis
      in the sandy soil in Daxing county area, the Beijing. METHOD: Small plot trial
      and Large-scale cultivation in the fields. RESULT AND CONCLUSION: Uralensis can
      be cultivated in the sandy soil in Daxing County area, Beijing.

PMID- 12212096
TI  - [Studies on chemical constituents of processed green tangerine peel].
AB  - OBJECTIVE: To study the chemical constituents of processed green tangerine
      peel(Citrus reticulata). METHOD: Using chemical techniques and spectroscopic
      analysis. RESULT: Four compounds were isolated from the peel and identified as
      hesperidin, neohesperidin, nobiletin and tangeritin. CONCLUSION: The compounds
      were obtained from this peel for the first time.

PMID- 12212098
TI  - [Flavonoids and anthraquinone from Dioscorea bulbifera L].
AB  - OBJECTIVE: To study the chemical constituents of Dioscorea bulbifera. METHOD:
      Column chromatography with silica gel was employed for the isolation and
      purification of constituents. The structures were elucidated by UV, IR, MS, 1H
      NMR and 13C NMR analyses. RESULT: Three compounds were obtained and elucidated as
      3,7-dimethoxy-5,4'-dihydroxyflavone; 3,7-dimethoxy-5,3',4'-trihydroxyflavone and
      emodin. CONCLUSION: These compounds were separated from D. bulbifera for the
      first time.

PMID- 12212097
TI  - [Studies on technology of supercritical-CO2 fluid extraction for volatile oils
      and saikosaponins in Bupleurum chinense DC].
AB  - OBJECTIVE: To study the technology of supercritical-CO2 fluid extraction (SFE
      CO2) for the volatile oils and saikosaponins in Bupleurum chinense. METHOD:
      Exploring the effects of pressure, temperature, extraction time, flow rate of CO2
      and entrainers on the yield of the oils and saikosaponin-contained extracts;
      determining the optimum conditions for SFE-CO2; analyzing the oils by GC/MS and
      comparing the technology of SFE-CO2 with that of traditional steam distillation.
      RESULT: The optimum extraction conditions turned out to be--for volatile oils:
      pressure (EP) = 20 MPa, temperature (ET) = 30 degrees C, isolator I pressure (1P
      I) = 12 MPa, temperature(1T-I) = 65 degrees C, isolator II pressure (1P-II) = 6
      MPa, temperature (1T-II) = 40 degrees C, extraction time = 4 hours, and CO2 flow
      rate = 10-20 kg.(h.kg)-1 crude drug; for saikosaponins: EP = 30 MPa, ET = 65
      degrees C, 1P I = 12 MPa, 1T I = 55 degrees C, 1P II = 6 MPa, 1T II = 43 degrees
      C, extraction time = 3 hours, entrainer = 60% ethanol, and CO2 flow rate = 20-25
      kg.(h.kg)-1 crude drug. CONCLUSION: SFE-CO2 excels the traditional steam
      distillation in raising yield and reducing extraction time. The oils are composed
      of 22 constituents including caproaldehyde, and the saikosaponins can only be
      extracted with the help of entrainers under higher pressure and temperature.

PMID- 12212099
TI  - [Studies on the effect-increasing components for molluscacides in nut of Areca
      catech L].
AB  - OBJECTIVE: To investigate the effect-increasing action of Areca catech for
      molluscacide. METHOD: Experiments were conducted on the effect-increasing
      components isolated from the dry nut of A. catech. RESULT: Arecoline has been
      proved the most effect-increasing component. CONCLUSION: When used with SPA
      arecoline could reduce markedly the doses of the two agents.

PMID- 12212100
TI  - [Studies on chemical constituents of Curcuma aromatica salisb].
AB  - OBJECTIVE: To study the effective ingredients of Curcuma aromatica. METHOD:
      Solvent extraction was used. The constituents were isolated with resin D-101
      silica gel column and thin-layer chromatography, and the structures were
      elucidated by physico-chemical properties and spectral analysis. RESULT:
      Curdione, neocurdione, curcumol, tetramethylpyrazine and (R)-(+)-1,2
      hexadecanediol were isolated from C. aromatica. CONCLUSION: Neocurdione and (R)
      (+)-1,2-hexadecanediol were isolated from C. aromatica for the first time, and
      was isolated from Curcuma and reported for the first time.

PMID- 12212101
TI  - [Isolation and identification of three steroid compounds from Mauremys mutics
      plastron].
AB  - OBJECTIVE: To investigate the steroids components from extract of Mauremys
      mutics. METHOD: The steroid compounds were isolated by using vacuum liquid
      chromatography and PTLC. The structures of three compounds were determined by
      spectral, chromatographic and chemical analysis. RESULTS: Three steroids were
      isolated from M. mutics and identified as cholesterol, elcosenoic acid
      cholesterol ester, cholester-4-ene-3-one. CONCLUSION: All the three compounds
      were isolated from M. mutics for the first time.

PMID- 12212102
TI  - [Determination of astragaloside IV in radix Astragali by HPLC with evaporative
      light scattering detector].
AB  - OBJECTIVE: To develop a new method for the determination of astragaloside IV in
      Radix Astragali. METHOD: A HPLC-ELSD method was set up, using Hypersil C18 column
      (150 mm x 4.6 mm), acetonitrile-water(1:2) as mobile phase with a flow rate of
      1.0 ml.min-1. The parameters of drift tube and gas flow rate of the detector were
      set at 105 degrees C and 2.96 L.min-1 respectively. RESULT: The calibration curve
      was linear in the range of 2.02-10.12 micrograms. The average recovery was
      100.5%. CONCLUSION: The active constituent astragaloside IV in Radix Astragali
      can be separated effectively. ELSD detection is appropriate for the determination
      of constituents with end absorption at low ultra-violet wavelengths.

PMID- 12212103
TI  - [Modulation of tonic herbs on the immune cell inhibition in stressed model animal
      and its possible mechanism].
AB  - OBJECTIVE: To observe the effect of tonic herbs on the immune cell proliferation
      in stressed mice. METHODS: A model of stressed mice was built to observe the
      effect of such tonic herbs as Tusizi, Chuanduan; Nuzhenzi, Gouqizi on the calcium
      concentration in cytoplasm in the process of immune cell reproduction, as well as
      on the membrane fluidity of splenetic lymphocytes, IL-2, IL-2R and cell period.
      RESULTS: The tonic herbs could improve the proliferation ability of spleen
      lymphocyte in the stressed mice, reduce the calcium concentration, and recover
      the fluidity of cell membrane. They could also improve the activity of IL-2 and
      increase the amount of IL-2R cell(P < 0.01). The combination of the four tonic
      herbs proved more effective, facilitating the cell into DNA synthetic period and
      reducing the retention period in G0/G1 (P < 0.01). CONCLUSION: Tonic herbs can
      modulate the reproductive function of the spleen lymphocyte and relieve the
      unfavorable response of the stress on the organism.

PMID- 12212104
TI  - [Effect of jiaweiyiguanjian decoction on hypothalamus-pituitary-thyroid gland
      (HPT) in rat model with Yin-deficiency of liver and kidney induced by slow
      irritation].
AB  - OBJECTIVE: To explore the mechanism of Jiaweiyiguanjian decoction in nourishing
      the liver and kidney. METHOD: A rat model with Yin-deficiency of liver and kidney
      was made by way of slow irritation. Thyrotropin-releasing-hormone(TRH) of thyron
      and blood, TSH of pituitary and blood, thyroxine, 3,5,3',5
      tetraiodothyronine(FT4) and 3,3',5-traiodothyronine(FT4), 3,3',5
      traiodothyronine(rT3) were used as indexes to study the effect of the decoction
      on HPT. RESULT: The TRH Secretion from hypothalamus increased (P < 0.05), TSH of
      pituitary and blood reduced(P < 0.05), FT3 and FT4 of blood decreased at the same
      time and rT3 of blood, increased. The indexes of the treatment group were found
      almost the same as the those of the normal control group. CONCLUSION:
      Jiaweiyiguanjian Decoction could adjust HPT.

PMID- 12212105
TI  - [Effect of chuanwu and baishao used separately or in combination on adjuvant
      arthritis in rats].
AB  - OBJECTIVE: To study the effect of Chuanwu(Aconitum carmichaeli) and
      Baishao(Paeonia lactiflora) used separately or in combination on the adjuvant
      arthritis in rats. METHOD: Chuanwu-Baishao decoctions of different proportions
      were orally administered to three different rat models with adjuvant arthritis to
      observe the preventing and curing actions on the primary and secondary adjuvant
      arthritis in rats. RESULT: The curing action on the primary adjuvant arthritis
      appeared the same whether the two ingredients were used separately or in
      combination, while on the secondary adjuvant arthritis the combination, produced
      significant preventing effect. Chuanwu was proved weaker in action when used
      alone Chuanwu and Baishao were very efficacious in curing adjuvant arthritics
      when used in combination other than separately. CONCLUSION: In preventing and
      curing the secondary adjuvant arthritis in rats Chuanwu and Baishao work better
      in combination.

PMID- 12212106
TI  - [Preliminary studies on chemotaxonomy of Caprifoliaceae L].
AB  - OBJECTIVE: To study the taxonomy of Caprifoliaceae. METHOD: Using
      chemotaxonomical methods to discuss the distribution characteristics of chemical
      constituents in Caprifoliaceae family. RESULTS: Iridoids and flavonoids were
      confirmed as the characteristic constituents of Caprifoliaceae family.
      CONCLUSION: Though there are great deviations among the genera of Caprifoliaceae
      family, it is not recommended to separate genus Sambucus and genus Viburnum from
      Caprifoliaceae family.

PMID- 12212107
TI  - [Cloning of the recombinant human hepatocyte growth factor gene].
AB  - The full length of HGF cDNA gene(2,184 bp) was amplified successfully from human
      placental tissue using RT-PCR technique, and then cloned into pGEM-T vector,
      which was identified and confirmed by restriction endonuclease mapping using Nde
      I, Bg1 II, Hind III, BamH I and Xho I, as well as DNA sequencing. The above clone
      of HGF cDNA gene was successfully subcloned into the retrovirus vector(pLNL-XHC),
      which may be used for further studies of gene expression and gene therapy.

PMID- 12212108
TI  - [The effects of exogenous p16 expression on CDK4, Cyclin D1 and pRb in
      nasopharyngeal carcinoma cell lines].
AB  - OBJECTIVE: To investigate the effect of exogenous p16 on Cyclin D1, CDK4 and pRb,
      and to explore the mechanism of the growth suppression of p16 in nasopharyngeal
      carcinoma cell lines. METHODS: The curve of cell growth rate in three kinds of
      HNE1, # 3-2 and # 4-2 cell lines was analyzed and their double time was compared.
      Then the distribution of the cell cycle was detected by flow cytometry. The
      expression of p16 and the effect of exogenous p16 expression on CDK4, Cyclin D1
      and pRb are studied by means of Western Blot. RESULTS: As compared with HNE1, # 3
      2 and # 4-2 showed a longer double time(23.4 h vs 28.8 h, 31.2 h). # 4-2 showed a
      significant accumulation of cells in G0/G1 phase(P < 0.01) and decreasing in S
      phase(P < 0.05) while HNE1 and # 3-2 had no obvious difference(P > 0.05). Cyclin
      D1 expression was upregulated in # 4-2 but downregulated in # 3-2 by exogenous
      expressed p16. No obvious difference on CDK4 expression was found.
      Hypophosphorylated pRb was detected in three cell lines. The expression was
      stronger in # 4-2, and # 3-2 than that in HNE1 and Hela. Hyperphosphorylated pRb
      was also detected in HNE1. CONCLUSION: Exogenous p16 expression may arrest cell
      cycle in G0/G1 phase and suppress cell growth. The major mechanism is not to
      regulate the level of the expression of CDK4. There might be a threshold in p16
      regulating Cyclin D1 expression. However, the final result contributes to the
      inhibition of pRb phosphorylation.

PMID- 12212109
TI  - [The mechanism of macrophage apoptosis induced by lipopolysaccharide in mice].
AB  - Apoptosis is a major form of cell death, characterized morphologically by
      chromatin condensation and biochemically by endonuclease cleavage of DNA into
      oligonucleosomal fragments. We investigated apoptosis mechanism of peritoneal
      macrophage(M phi) induced by peritoneal injection of lipopolysaccharide(LPS) in
      mice. The results showed that: LPS induced the apoptosis of peritoneal M phi and
      concomitant decrease of phagocytosis(vs control group, P < 0.01), the
      concentration of NO2-/No3- in the peritoneal lavage fluid significantly increased
      after LPS injection; AG(inhibitor of iNOS) and PDTC(inhibitor of reactive oxygen
      species) prevented the apoptosis of M phi and reduced the concentration of NO2
      /NO3- in the peritoneal lavage fluid. In vitro experiment, we found that AG and
      PDTC inhibited the apoptosis of M phi induced by IFN(100 U.ml-1) + LPS (10
      micrograms.ml-1) by using DNA gel electrophoresis analysis. These evidences
      support that NO and active oxygen species may be involved in the apoptosis
      process of peritoneal M phi induced by LPS in mice.

PMID- 12212110
TI  - [The effects of a novel aminosteroid on WEHI-3B leukemia cells].
AB  - OBJECTIVE: To evaluate the effect of a novel aminosteroid(KH) on WEHI-3B cells.
      METHODS: The effects and mechanism of KH on proliferation, differentiation and
      apoptosis of WEHI-3B cells in vitro were studied by semi-solid colony culture,
      MTT assay, morphologic examination, NBT reduction test, NSE assay, DNA
      fragmentation in gel electrophoresis and RT-PCR of c-myc oncogene. RESULTS: The
      growth of leukemic colony was inhibited by KH(10(-8)-10(-4) mol.L-1) after
      treatment of KH for 7 days. The percentages of NBT and NSE positive cells were
      increased from 40.38% to 71.17% and 48.25% to 79.25%, respectively as well as the
      typical ladders of DNA fragments in gel electrophoresis were also observed after
      WEHI-3B cells were treated with KH(10(-8)-10(-4) mol.L-1) for 5 days. The c-myc
      mRNA expression of WEHI-3B cells was decreased by 58.7% after WEHI-3B cells were
      treated with KH(10(-8) mol.L-1) for 5 days. CONCLUSION: KH might suppress the
      proliferation of WEHI-3B cells, induce the differentiation of WEHI-3B cells into
      macrophage-like cells and facilitate the cell apoptosis. There is relationship
      between the above effects and c-myc mRNA expression of WEHI-3B cells.

PMID- 12212111
TI  - [Analysis of ultrasonography on menopausal endometrium diseases].

PMID- 12212112
TI  - [Influence of human cytomegalovirus infection on the expression of HOX genes in
      human embryo lung cells].
AB  - The expressions of HOX genes in human embryo lung (HEL) cells were detected with
      semi-quantitative RT-PCR method. The results were that HEL cells expressed HOXB7
      gene and its expression increased after human cytomegalovirus (HCMV) infection.
      The level of expression reached maximum at 48 h after HCMV infection. Treated
      with all-trans retinoic acid (ATRA), the expression of HOXB7 in HEL cells
      infected by HCMV was significantly increased. The results suggest that the
      abnormal expression of HOX genes induced by HCMV might possibly play a role in
      virus-induced abnormal embryogenesis.

PMID- 12212113
TI  - [The anti-leukemia effect of Sophora flavescens and its mechanism].
AB  - By using CFU-GM/CFU-L colony assay, NBT/MTT reductant test and DNA fragmentation
      analysis, we studied the effects of Sophora flavescens (SF) on CFU-GM
      proliferative ratio in human normal bone marrow/umbilical cord blood and on
      proliferation, differentiation and apoptosis in human acute myelogenous leukemia
      HL-60 cells. The results showed that 5, 10, 15, 20 micrograms.microliter-1 of SF
      significantly inhibited proliferation and induced apoptosis in the HL-60 cells in
      a dose-dependent fashion. Fifteen micrograms.microliter-1 of SF also induced
      differentiation in HL-60 cells. Furthermore, cytotoxic activity of SF(5-15
      micrograms.microliter-1) was not apparent on human normal hematopoietic
      progenitors(CFU-GM). The results indicate that an appropriate concentration of SF
      has a selective antileukemic effect. Thus, these are important impetuses for
      further research of SF as an anticancer agent.

PMID- 12212114
TI  - [A case-control study on the risk factors for preterm delivery].
AB  - The risk factors for preterm delivery were analyzed with 1:2 matched case-control
      study by conditional logistic regression analysis. The result showed that the
      main risk factors for preterm delivery were neuroticism scores, premature rupture
      of the membranes, husband's smoking frequency during the third trimester of
      pregnancy, pregnancy induced hypertension, working strength and first-trimester
      vaginal bleeding. It is indicated that an examination before delivery and gaining
      weight during pregnancy are helpful to decrease the occurrence of preterm
      delivery.

PMID- 12212115
TI  - [Clinical investigation of effects of bizhongxiao decoction (BZX) on rheumatoid
      arthritis on active phase].
AB  - Ninety-six patients with rheumatoid arthritis(RA) on active phase were divided
      into BZX-treated group(BZXG) and methotrexate-treated group(MTXG). The results
      showed that after 1-month treatment, symptoms and signs, such as joint
      tenderness, arthralgia, arthroncus, of patients in BZXG improved notably(P < 0.01
      or P < 0.05), while those of patients in MTXG did not improve, there was
      significant difference between these two groups(P < 0.01 or P < 0.05). After 3
      month treatment, these symptoms and signs improved in both groups(P < 0.01 or P <
      0.05), but BZX had a better effect than MTX. ESR, CRP, RF, C3, IgG, IgA and IgM
      decreased significantly in both groups after treatment(P < 0.01 or P < 0.05),
      ESR, CRP in BZXG decreased more and faster than those in MTXG. In BZXG the
      obviously efficient rat was 70%, the total efficacy rate was 94%, while in MTXG
      was 52% and 87% respectively. It is indicated that BZX can improve symptoms and
      signs of patients with RA, has better and faster effects on acute phase reaction
      than MTX; and it has anti-immunologic effects similar to MTX, and has no obvious
      side effect.

PMID- 12212116
TI  - [Expression of bcl-2 in the normal endometrium and endometrium of adenomyosis].
AB  - Using immunohistochemical ABC staining, we detected the expression and role of
      bcl-2 in normal endometrium(n = 17) and eutopic and ectopic endometrium with
      adenomyosis(n = 16) during the menstrual cycle. The first result was that the
      expressions of bcl-2 in the eutopic endometrium were the same as the normal
      endometrium, showing predominantly in the glandular epithelial cells, and
      obviously cyclic changes throughout the menstrual cycle. This result suggests
      that these changes may be regulated by ovarian hormone and play an important role
      in the proliferation and physiologic death of normal endometrial glandular
      epithelial cells to regulate the menstrual cycle. Bcl-2 expression in the
      glandular cells of ectopic endometrium of adenomyosis had no cyclic change and
      bcl-2 staining had remained in the whole menstrual cycle. The second result
      suggests that the above mentioned phenomena may play an important role in the
      pathogenesis of adenomyosis.

PMID- 12212117
TI  - [The effect of FHIT gene on renal cell carcinomas].
AB  - OBJECTIVE: To study the potential role of FHIT gene in renal cell carcinomas.
      METHODS: Cancerous tissues derived from 23 patients with renal cell carcinomas
      and an established cell line were examined for the alteration of FHIT gene
      transcripts and structure of genomic DNA by using RT-PCR and Southern blot
      hybridization assays. RESULTS: Eight point three percent(2/24) of cancerous
      tissues exhibited aberrant transcripts. The transcript in the renal-cell cancer
      cell line appeared a small-size one when cDNA was amplified with outside nest
      primer; absent expression of transcript was shown when amplified with inside nest
      primer. About twenty percent(5/24) cancerous tissues showed genomic rearrangement
      in FHIT gene locus. CONCLUSION: FHIT gene exhibited aberrant transcripts and
      genomics in some of renal cell cancers. Therefore change of FHIT gene may play a
      role in development of renal cell carcinomas.

PMID- 12212118
TI  - [Variation of blood lipids and circulatory endocrine factors in patients with
      acute myocardial infarction].
AB  - OBJECTIVE: To observe the dynamic variations of blood lipids and circulatory
      endocrine factors in acute myocardial infarction(AMI) patients. METHODS: We
      determined plasma levels of ET-1, ANP, insulin and serum lipids on the 1st, 3rd,
      7th and 14th day in 41 patients with acute myocardial infarction. RESULTS: The
      serum levels of TC, LDL-C obviously decreased from the 3rd to the 7th day, and
      gradually elevated on the 14th day. The serum level of TG elevated gradually and
      showed significant difference after one week. HDL-C had no significant
      difference. The levels of ET-1 and insulin increased to highest level on the 1st
      day and decreased gradually since then. However, ANP reached the highest value on
      the 3rd day, and decreased markedly in fourteen days later. On the 1st day, only
      the concentration of insulin was negatively related with serum levels of TC, LDL
      C(r = -0.376, -0.388, respectively, P < 0.05). The concentrations of blood lipids
      weren't related with circulatory endocrine factors during other phases.
      CONCLUSION: The primary characteristics of blood lipids dynamic variations are
      the decrement of TC, LDL-C and the increment of TG during acute phase of AMI.
      Meanwhile, the concentrations of ET-1, ANP and insulin present dynamic variations
      and may effect the metabolism of blood lipids through some cytokines.

PMID- 12212119
TI  - [The vitronectin anchors on placenta tissue of hypertensive pregnancy].
AB  - Using immunohistochemistry staining and Western-blot techniques, we detected the
      distribution and content of vitronectin antigen in placenta tissue of one case of
      hypertensive pregnancy in order to explore pathogenesis of the development of
      hypertensive pregnancy. The results were that vitronectin expressions on
      hypertensive pregnant placenta were obviously higher than those on normal
      placenta, which suggests that fibrin deposition on placenta tissue was associated
      with suppression of fibrinolysis.

PMID- 12212120
TI  - [Anatrophic nephrolithotomy through intersegmental line for the treatment of
      stagborn renal stone].

PMID- 12212121
TI  - [Effects on ang II receptor antagonist on experimental glomerulosclerosis].
AB  - OBJECTIVE: To observe the effects of angiotensin II receptor antagonist losartan
      in experimental glomerulosclerosis. METHODS: The 5/6 nephrectomized rats were
      randomly divided into losartan treatment group and control group, the rats with
      sham operation served as normal control. Urine proteins were measured in the 2nd,
      4th and 6th week after operation, and serum BUN, creatinine, total protein and
      albumin were measured in the 6th week following operation. Renal pathologic
      changes were evaluated in the 6th week. RESULTS: Losartan not only reduced urine
      protein, serum creatinine and BUN(P < 0.01), but also significantly ameliorated
      glomerular mesangial proliferation and glomerular sclerosis. CONCLUSION: The
      results suggest that losartan can retard progression of glomerulosclerosis in 5/6
      nephrectomized rats.

PMID- 12212122
TI  - [Expression of different receptors of the apoptosis inducing gene TRAIL in human
      ovarian tumors].
AB  - Reverse transcriptase polymerase chain reaction (RT-PCR) was applied to assay
      mRNA expression of TRAIl(the TNF related apoptosis inducing ligand) receptors
      (DR5, DcR1, and DcR2) in 3 cases of normal ovarian tissues, 6 cases of ovarian
      benign tumors, and 16 cases of ovarian cancers. Peripheral blood lymphocytes were
      used as a positive control. Positive expression of the DR5 and DcR1 were found in
      peripheral blood lymphocytes and 3 cases of normal ovaries. Positive expressions
      of the DR5 and DcR1 were 83.3%(5/6) in benign ovarian tumors and 68.8%(11/16) in
      ovarian cancers respectively. Positive expression of the DcR2 was only found in
      normal ovaries and benign tumors. These findings suggest that expression of
      different receptors may play an important role in the apoptosis regulation of
      ovarian tumors, especially DcR2.

PMID- 12212123
TI  - [Effects of myocardial ischemia on 24-hour QT interval variability].
AB  - OBJECTIVE: To explore the significance of QT variability in myocardial ischemia.
      METHODS: Twenty-four-hour QT interval variability in 37 patients with myocardial
      ischemia and 42 patients without myocardial ischemia were measured with 24-hour
      Holter recordings. RESULTS: QT interval variability in patients with myocardial
      ischemia was larger than that in patients without myocardial ischemia.
      CONCLUSION: Myocardial ischemia can influence QT interval variability.

PMID- 12212124
TI  - [5 cases of hemolytic transfusion reactions induced by anti-E].

PMID- 12212125
TI  - [Change of bone mineral density in type 2 diabetes mellitus with nephropathy].
AB  - OBJECTIVE: To investigate into the changes of bone mineral density(BMD) in Type 2
      diabetes mellitus with nephropathy(DN) and without nephropathy(DM). METHODS: BMD
      of lumbar vertebrae 1-4 and femur in 93 cases of Type 2 diabetes mellitus(41
      cases of DN and 52 cases of DM) were measured with dual energy x-ray
      absorptiometry(DEXA) and were compared with age, sex, and BMI-matched normal
      control group. RESULTS: No significant differences were found in BMD of femoral
      total, neck, L1-L4 between DM and normal controls in females(P > 0.05). DM in men
      had higher BDM at L2, femoral total neck than normal controls(P < 0.05). BMD at
      femoral total, neck, in females and L1-L4 femoral total neck in men in DN group
      were lower than DM group, but had no statistical differences. CONCLUSION: The
      changes in BMD of above areas in DM were normal and higher because of different
      areas. BMD in DN had lower predisposition.

PMID- 12212126
TI  - [The effects of jiexinkang on the apoptosis of leukemic cells].
AB  - The effects of Chinese medicine jiexinkang(JXK) on apoptosis of leukemic cells
      were studied by morphology approach and electrophoresis of DNA fragments.
      RESULTS: 1. The apoptotic cells and apoptotic bodies were found by electrical
      microscopy and the typical ladders of DNA fragments were detected by
      electrophoresis. 2. JXK induced apoptosis of leukemic cells(HL-60 and K562) in a
      certain range of concentration and at appropriate time. The time to K562 cell
      apoptosis was longer than that of HL-60 and its dosage was larger than that of HL
      60. CONCLUSION: HL-60 and K562 leukemic cell apoptosis may be induced by JXK and
      there is correlation between dose and time. The study provides experimental
      evidences for the clinical treatment of leukemia.

PMID- 12212127
TI  - [Protective effects of low dose nitric oxide inhalation on lung
      ischemia/reperfusion injury during cardiopulmonary bypass surgery].
AB  - OBJECTIVE: Out aim is to study the effects of inhaling nitric oxide(NO) on the
      pulmonary ischemia/reperfusion injury during cardiopulmonary bypass surgery.
      METHODS: Cardiac valve replacement was performed on twenty patients with chronic
      rheumatic heart valve disease under cardiopulmonary bypass, and they were
      randomly divided into two groups: control group(n = 10) and NO group(n = 10). We
      monitored the following: mean pulmonary arterial pressure(MPaP), pulmonary
      vascular resistance(PVR), peak airway pressure (PAP), cyclic guanosine
      monophosphate(cGMP), inter-cellular adhesion molecule-1(ICAM-1), xanthinoxidase
      (XOD), malondialdehyde(MDA), PaO2 and the duration of post-operative mechanical
      ventilation. RESULTS: The PAP, MPaP and PVR in the control group were much higher
      than those in NO group after reperfusion(P < 0.05). The durations of
      postoperative mechanical ventilation in NO group were shorter than those in the
      control group(P < 0.01). The cGMP and PaO2 after reperfusion in NO group were
      higher(P < 0.01), and the ICAM-1, XOD, MDA were lower(P < 0.05) than those in the
      control group. CONCLUSIONS: 1. If aortic clamp time is over 1 h, lung
      ischemia/reperfusion injury may occur during cardio-pulmonary bypass surgery. 2.
      Inhaling 20 ppm NO in the early phase of reperfusion has protective effects on
      the lung ischemia/reperfusion injury during cardio-pulmonary bypass surgery. 3.
      The mechanisms of the protective effects may be related with the increase of cGMP
      and the decrease of ICAM-1, XOD, MDA.

PMID- 12212128
TI  - [Repair of cardiac defects by minimal incision without aortic cross-clamp].
AB  - From July 1998 to June 1999, seventy two patients underwent repair of congenital
      heart defects by a partial sternal split and a limited skin incision(4-8 cm)
      under cardiopulmonary bypass without aortic cross-clamp at our institution. The
      average age of these patients was 4 years and 5 months(range: 7 months to 12
      years), and the average weight was 15.6 kg(range: 7 kg to 30 kg). Fifty six
      patients had simple ventricular septal defects, sixteen suffered from atrial
      septal defects. The average bypass time was (21 +/- 20) min (range: 8-58 min).
      All patients recovered rapidly from the operation in an uneventful postoperative
      course. Our experience demonstrates that this technique is feasible and can be
      performed easily in young children with simple cardiac defects, and has excellent
      cosmetic results.

PMID- 12212129
TI  - [Dynamic changes of serum lipids in patients with acute stroke].
AB  - The dynamic changes of the serum levels of total cholesterol(TC),
      triglyceride(TG), high density lipoprotein-cholesterol(HDL-c) and
      subfraction(HDL2-c), apolipoprotein(Apo) A-I, ApoB, lipoprotein(a)[Lp(a)] and
      fibrinogen(Fg) were measured in forty-one patients with acute[including 31
      cerebral hemorrhagic patients(ICH), and 10 cerebral infraction patients(CI)]. The
      results showed that the serum levels of HDL-c and subfractions, ApoA-I and TC
      gradually decreased in ICH during acute phase, and reduced to the lowest level on
      the fourteenth day, while the levels of TG and ApoB had no obvious change, the
      serum levels of Fg and Lp(a) increased to the highest level on the seventh day.
      The serum levels of Lp(a), ApoB and TG had no obvious change in CI during acute
      phase, and the serum levels of TC, HDL-c and subfraction, ApoA-I decreased, while
      the level of Fg increased in CI, but there was no statistical significance. It is
      suggested that Lp (a) is a positive acute reactive lipoprotein in ICH, and HDL
      and ApoA-I are negative acute reactive substances in ICH and CI.

PMID- 12212130
TI  - [Determination of vanillymandelic acid in urine by high performance liquid
      chromatography].
AB  - OBJECTIVE: To develop a high performance liquid chromatography(HPLC) for
      determining vanillylmandelic acid(VMA) in urine. METHODS: The analytical column
      was packed with Nova-Pak C18. Flow rate was 0.9 ml.min-1. The mobile phase was 40
      mmol.L-1 NaH2PO4 buffer. The VMA of 30 healthy people in 24 hour urine were
      tested by the internal standard method and with electrochemical detector. RESULT:
      The linear range was from 5 mumol.L-1 to 200 mumol.L-1. The mean analytical
      recovery rate was 99.1%. The mean within-day coefficient of variation(CV) was
      5.8%, and the mean day-to-day CV was 7.7%. The detection limit was 0.28 mumol.L
      1. The VMA of 24 hour urine was 18.13 +/- 6.17 mumol in healthy people.
      CONCLUSIONS: The method is suitable for routine determination of VMA in urine.

PMID- 12212131
TI  - [Clinical analysis of 318 cases of new-mode cesarean section].
AB  - OBJECTIVES: To study types of new mode cesarean section (CS) and its clinical
      value. METHODS: Four hundred and sixty-eight pregnant women with operative
      indications were randomly divided into three groups: the new mode CS group whose
      peritoneum was not sewed, the new mode CS group whose peritoneum was sewed, and
      the lower segmental CS group. The duration of operation, bleeding volume,
      morbidity after operation, and B type ultrasound for examining the incision were
      observed. RESULTS: There were significant difference in the duration of
      operation, bleeding volume, and morbidity after operation between the lower
      segmental CS and the two types of the new mode CS (P < 0.05). There was no
      significant differences in the bleeding volume and morbidity after operation
      between the two types of the new mode CS (P > 0.05), but there were significant
      difference in the duration of operation and the incision examined by B type
      ultrasound (P < 0.05). CONCLUSION: The new mode CS has shorter operative period,
      less bleeding, weak pain, faster recovery of peristalsis, and lower incidence of
      post-operative morbidity.

PMID- 12212132
TI  - [A case of anesthetic management of pigback orthtopic liver transplantation].

PMID- 12212133
TI  - [A clinical study on male patients with systemic lupus erythema].
AB  - To know the clinical characteristics of male patients with systemic lupus
      erythema(SLE), the clinical and laboratory indications of 46 male SLE patients
      were analysed and compared with those of 269 females. The results showed that: 1.
      There was family history in 21.28% of male patients. 2. As compared with female
      SLE patients, pleurisy, pericarditis, lupus nephritis(LN), proteinuria, renal
      failure, the incidence of types, V-LN and the positive rate of Sm antibody were
      more common in males while facial erythema, Raynaud's phenomenon and photoallergy
      were less in male. There were statistical differences between the male and
      female. 3. The confirmed diagnosis for the male SLE was delayed. The recovery
      rate was lower and the mortality was higher in males. These findings suggest that
      evident genetic predisposition, atypical clinical manifestations, serious renal
      injury and the worse prognosis are the characteristics of male SLE.

PMID- 12212134
TI  - [A study of quality standards for fuyanke granule].
AB  - OBJECTIVE: To establish the quality standards for fuyanke(FYK) granule. METHODS:
      The phellodendron Chinese schneid, polygonum cuspidatum, sieb. et Zucc and
      glycyrrihza uralensis fisch in FYK granule were identified by thin-layer
      chromatography(TLC). The contents of berberine were determined by thin-layer
      chromatographic scanning(TLCs). RESULTS: The average recovery rate was 97.86%,
      and the relative standard deviation 1.96%. CONCLUSION: The method is simple,
      accurate and reliable.

PMID- 12212135
TI  - [Morphologic and histochemical characteristics of the dental cuticle on the teeth
      affected by periodontitis in juvenile].

PMID- 12212136
TI  - [Influence on immune function of mice by instillating BCG-PSN intravesically].

PMID- 12212138
TI  - [Indocyanine green angiography in traumatic choroids rupture].

PMID- 12212137
TI  - [Erythrocyte membrane adenosine triphosphatase activity determination in patients
      with liver-yin deficiency syndrome].

PMID- 12212139
TI  - [Short-term therapy of terbinafine for superficial cutaneous mycosis].

PMID- 12212140
TI  - [Expression of P53, bcl-2 protein and proliferating cell nuclear antigen in
      cutaneous squamous cell carcinoma].

PMID- 12212141
TI  - [Levels of serum soluble tumor necrosis factor receptor in patients with lung
      cancer].

PMID- 12212143
TI  - [Clinical analysis on 29 cases of aortic dissection].

PMID- 12212142
TI  - [Relation between the cerebral ischemia pre-conditioning and hippocampal
      pyramidal apoptosis].

PMID- 12212144
TI  - [Effect of qingkailing on glutamate and NMDA receptor of brain tissue].
AB  - The effects of QingKaiLing on the content of glutamate(Glu) and gamma
      aminobutyric acid(GABA), and the numbers and affinity of N-methyl-D-aspartate
      (NMDA) receptor in brain tissue were observed. QingKaiLing did not change the
      content of Glu and GABA and the ratio of Glu/GABA in brain tissue (P > 0.05). The
      numbers of NMDA receptor on membrane of neuron were significantly decreased in
      QingKaiLing group(P < 0.05). These results suggested that the brain protective
      mechanism of QingKaiLing be in relation to decreasing the numbers of NMDA
      receptor.

PMID- 12212145
TI  - [Effect of curcumin on the proliferation of murine CFU-GM and WEHI-3B cells].
AB  - OBJECTIVE: To evaluate the effect of curcumin on the proliferation of
      hematopoietic progenitor cells or leukemic stem cells. METHODS: Mouse bone marrow
      cells (colony forming unit-granulocyte and macrophage, CFU-GM) and WEHI-3B cells
      were observed using the colony assays. RESULTS: The curcumin significantly
      inhibited the proliferation of both CFU-GM and WEHI-3B cells in a dose-dependent
      manner ranging from 10(-8) to 10(-4) mol.L-1; their IC50S were 1.036 x 10(-5)
      mol.L-1 and 1.220 x 10(-6) mol.L-1 of curcumin respectively. CONCLUSION: The
      proliferation of murine CFU-GM and WEHI-3B cells can be suppressed by curcumin.
      The inhibitory effect of curcumin on the proliferation of WEHI-3B cells is
      stronger than that of CFU-GM.

PMID- 12212146
TI  - [The roles of alpha B-crystallin during early phase of myocardial ischemic
      preconditioning in rats].
AB  - OBJECTIVE: This study designed to observe intracellular translocation of alpha B
      crystallin, a small heat shock protein, and its possible implication during the
      early phase of myocardial ischemic preconditioning in isolated Langendorff rat
      hearts. Eighteen male Wistar rats(180-250 g) were randomly divided into three
      groups: 1. Control group(Ctrl) was perfused with K-H solution throughout the
      experiment; 2. ischemia-reperfusion group (I-R) experienced 30 min of global
      ischemia and 120 min of reperfusion and 3. preconditioning and ischemia
      reperfusion group(PC + I-R) was preconditioned with three cycles of short
      myocardial ischemia(5 min each, separated by 5 min of reperfusion) prior to 30
      min of ischemia and 120 min of reperfusion. It was showed that cytosolic soluble
      alpha B-crystallin rapidly translocated to insoluble intracellular structure
      after ischemic preconditioning, then gradually returned to soluble cytosol pool
      and almost completely recovered at about 60 min after preconditioning. In the
      meanwhile, ischemic preconditioning markedly alleviated subsequent myocardial
      ischemia-reperfusion injury, as indicated by the improvement of LVP, + dp/dt max,
      coronary flow, heart rate, CPK release and malondialdehyde(MDA) production. The
      results suggest that the intracellular translocation of alpha B-crystallin might
      be important for myocardial protection during the early phase of ischemic
      preconditioning.

PMID- 12212147
TI  - [Heat shock pretreatment increases alpha B-crystallin expression and protects
      cardiomyocytes against injury induced by hydrogen peroxide].
AB  - The protective effects of heat shock pretreatment against the injury induced by
      hydrogen peroxide(H2O2) were evaluated in neonatal rat cardiomyocytes. The
      results showed that heat shock pretreatment significantly reduced cell mortality
      rate, LDH release rate and increased total antioxidation of the cells. Western
      blot analysis demonstrated that heat shock pretreatment induced expression of
      alpha B-crystallin and immunoelectron microscopy demonstrated H2O2-mediated alpha
      B-crystallin translocation from cytoplasm to nucleus and microfilament in
      cardiomyocytes. The results suggest that the mechanism of protective effect of
      heat shock pretreatment might involve the induction and translocation of alpha B
      crystallin which then protect cardiomyocytes against H2O2-induced injury by
      stabilizing cytoskeletal structure and increasing anti-oxidation capacity of the
      cells.

PMID- 12212148
TI  - [Cloning and analysis of different regions of SRY promoter].
AB  - The luciferase systems were used to assay the promoter activity of SRY gene with
      clones of different parts of the 5' flanking region within 544 bp which has basal
      promoter activity. The results were that the 179 bp region from nt. -353 to nt. 
      174 upstream of the first ATG included a silent element; the 49 bp region from
      nt. -112 to nt. -63 included an enhanced element and the 63 bp region from nt. 
      174 to nt. -112 included an essential promoter sequency for gene transcription.
      These results give some important clues to elucidate the expression and
      regulation mechanisms of SRY gene.

PMID- 12212149
TI  - [The electron probe microanalysis on oral precancer treated by garlic].
AB  - OBJECTIVE: To evaluate the effect of 4 kinds of trace elements on experimental
      oral precancer treated by garlic. METHODS: The palatal mucosae of 42 Wistar rats
      were painted with 0.5% of 4-nitroquinololine-1-oxide(4NQO) three times weekly for
      7 weeks by coating method. Then the animals were divided randomly into two
      groups. The treatment group was treated three times weekly with garlic solution
      at the posterior hard palatal mucosae by coating method, and in the control
      group, the vehicle-distilled water was used instead of garlic solution. At the
      5th and 8th weeks of the treatment and the 7th week after the treatment was
      stopped, some animals were killed. The palatal epithelial cells were prepared and
      surveyed by electron probe microanalysis. RESULTS: During the treating period,
      garlic improved the levels of epithelial cells' nuclei copper, selenium,
      molybdenum and extranuclei selenium, molybdenum(P < 0.01), but it decreased the
      contents of epithelial cells' extranuclei copper and extra- and intranuclei
      zinc(P < 0.01). CONCLUSIONS: Garlic can treat the oral precancer by improving the
      levels of epithelial cells' nuclei copper, selenium, and molybdenum and
      extranuclei selenium and molybdenum.

PMID- 12212150
TI  - [Model of diffuse axonal injury and focal brain injury in rats].
AB  - OBJECTIVE: To establish a rather ideal experimental brain injury model in rats,
      in which diffuse axonal injury(DAI) and focal brain contusion were made
      concurrently. METHODS: The pathophysiological changes were monitored, and the
      histological changes were observed under naked eye, microscope and electric
      microscope. RESULTS: 1. The mortality in the group suffering from DAI with focal
      contusion(Group A) was much higher than that in DAI(Group B) and sham group(Group
      C); 2. The time of post-injury primary coma in Group A [(5.19 +/- 0.49) h] was
      longer than that in Group B [(2.75 +/- 0.16) h] and Group C [(2.77 +/- 0.20) h]
      significantly(P < 0.01); 3. Immunohistological examination showed that the
      diffuse axonal injury could be seen in several parts of the brain(subcortical,
      corpus callosum and brainstem) in Group A; 4. We observed in Group A under
      electric microscope that the axons were swollen and degenerated fragmently,
      neurofilaments ranged disorderly and there was vacuolation. CONCLUSION: The model
      is cheap, simple and can be easily repeated. Furthermore it can be used to
      research the changes of pathophysiology, histology and moleculobiochemistry of
      head injury in human beings.

PMID- 12212151
TI  - [A case of infection-associated hemophagocytosis syndrome].

PMID- 12212152
TI  - [Study of the risk factors of blood pressure in children].
AB  - The blood pressure of 495 normal children aged nine to fourteen years were
      measured. The body height, weight, blood lipid profile, fasting blood
      glucosum(FBS) were also measured. The children's family history of hypertension
      and their dietary status and physical exercise status were investigated. The
      results showed that the older the child, the higher the blood pressure. On single
      factor analysis, systolic blood pressure (SBP) was positively correlated with
      age, family history of hypertension, intake of whole lipid milk, body height,
      weight, BMI, blood TC, LDL-C and FBS, whereas it was negatively correlated with
      the time of physical exercises and blood HDL-C/TC. Diastolic blood pressure(DBP)
      was positively correlated with age, body height, weight, IBM, FBS, blood TC and
      LDL-C, whereas it was negatively correlated with blood HDL-C/TC. Multifactor
      regression analysis showed that weight, age, blood TC and FBS had significant
      effects on SBP, while weight, age, blood TC and LDL-C had significant effect on
      DBP. Therefore, avoiding obesity, improving dietary status, taking more physical
      exercises and suitably lowering blood lipid and FBS should be carried out in
      children.

PMID- 12212153
TI  - [Experimental study on Jurkat cell apoptosis induced by Boswellia carterii Birdw
      extractive].
AB  - OBJECTIVE: To study the influence of Boswellia carterii Birdw(BCB) extractive of
      different concentrations on human Jurkat cell apoptosis at different time points.
      METHODS: Agarose gel electrophoresis, transmission electron microscope(TEM) and
      flow cytometry(FCM) were used for observing DNA ladders, morphology of Jurkat
      cells and cell cycle, respectively. RESULTS: BCB induced apoptosis of Jurkat
      cells and typical DNA ladders; TEM demonstrated the presence of apoptosis Jurkat
      cells, condensation of cytoplasm, numerous vaculoes in cytoplasm, compaction of
      the nuclear chromatin and formation of apoptosis dody. The sub-G1 peak was
      detected by cell cycle analysis. It revealed that G1 phage cells increased and S
      phage cells decreased. CONCLUSION: The data indicate that BCB extractive induces
      time- and concentration-dependent apoptosis in Jurkat cell line.

PMID- 12212154
TI  - [Protective effect of traditional Chinese medicine nao-yi-an granule in
      experimental rats with hemorrhagic stroke].
AB  - In order to establish a model of intracerebral hemorrhage(ICH), 0.4 U bacterial
      collagenase was injected stereotaxically into globus pallidus in rats.
      Neurological deficit score was investigated, and inducible nitric oxide
      syntahse(iNOS) mRNA was detected in 72 rats. The results showed that: in the
      group treated by nao-yi-an granule(NYA), the recovery time was shorter than that
      in other groups, and low concentration nitrite and weak signal of iNOS mRNA were
      found. It suggests that inhibition of iNOS induction is one of the
      pharmacological effects of NYA.

PMID- 12212155
TI  - [Effects of cordyceps sinensis on T lymphocyte subsets and hepatofibrosis in
      patients with chronic hepatitis B].
AB  - In order to find an effective drug to cure patients with chronic hepatitis B,
      cordyceps sinensis had been used to treat 25 patients with chronic hepatitis B.
      The comprehensive index, including T lymphocyte subsets (CD4, CD8), hyaluronic
      acid(HC) and precollagen type III(PC III), were observed before and after
      treatment. After 3 months of treatment, CD4 and CD4/CD8 ratio increased
      significantly(P < 0.05), while HA and PC III decreased significantly(P < 0.05)
      compared with the control. The results suggest that the beneficial effects might
      be obtained by using cordyceps sinensis to adjust the T lymphocyte subsets level
      and to treat hepatic fibrosis on patients with chronic hepatitis B.

PMID- 12212156
TI  - [The efficacy of parenteral nutrition with different energy for systemic
      inflammatory response syndrome (SIRS) in the aged].
AB  - To evaluate the efficacy and safety of parenteral nutrition (PN) with lower or
      higher energy for treating systemic inflammatory response syndrome (SIRS) in the
      aged, thirty old SIRS critically ill patients were involved in a randomized
      control clinical trial. Fifteen cases were treated by PN with lower energy (105
      KJ.kg-1.d-1), and another fifteen cases with higher energy (146 KJ.kg-1.d-1) for
      6 days. The data about metabolisms of protein, glucose and fat, blood gas
      analysis, acute physiology and chronic health evaluation (APACHE II) were
      analysed. The results showed that: 1. The effects of 105 KJ.kg-1.d-1 PN in
      increasing organism protein and maintaining nitrogen balance were the same as
      those of 146 KJ.kg-1.d-1 PN. 2. The levels of fast blood sugar and triglyceride
      maintained unchanged in 105 KJ.kg-1.d-1 PN group, while they increased
      significantly in 146 KJ.kg-1.d-1 PN group(P < 0.05). 3. PaO2 was raised greatly
      in 105 KJ.kg-1.d-1 PN group, while not in 146 KJ.kg-1.d-1 PN group. 4. 105 KJ.kg
      1.d-1 PN and 146 KJ.kg-1.d-1 PN decreased APACHE II(P < 0.05), but the efficiency
      of 105 KJ.kg-1.d-1 PN was better than that of 146 KJ.kg-1.d-1 PN (P < 0.05). We
      conclude that PN with 105 KJ.kg-1.d-1 energy intake is more effective and safer
      for treating SIRS than that with 146 KJ.kg-1.d-1 in the aged.

PMID- 12212157
TI  - [Efficacy of radiotherapy combined with Traditional Chinese medicine (TCM) in NPC
      patients].
AB  - From January 1992 to November 1994, 163 patients with nasopharyngeal carcinoma
      (NPC) were prospectively randomized into three groups: standard radiotherapy
      (SRT) group, external irradiation and after-load intracavitary radiation in
      combination with traditional Chinese medicine (EIAIRC) group, and external
      irradiation plus traditional Chinese medicine (EIC) group. All patients were
      treated with usual radiotherapy. The nasopharynx's radiation dose was 50-60 Gy,
      intracavitary irradiation 16 Gy/2 times (The distance from radiation source to
      spot of reference was 14 mm away). The radiation dose in EIC and SRT group was 68
      72 Gy, respectively. The results were as follows: 1. There were no statistical
      difference among the three groups in 3-year or 5-year survival rate and no local
      relapse or distant metastasis. 2. The TCM alleviated the acute radiation reaction
      and damage effects. It indicates that the therapy might decrease radiation dose
      and the TCM does not induce NPC distant metastasis.

PMID- 12212158
TI  - [A case of common bile duct polyps diagnosed by ultrasonography].

PMID- 12212159
TI  - [Reconstruction of forearm function by fibular transfer with vascular
      anastomoses].
AB  - OBJECTIVE: To analyse and report the reconstruction of forearm function by
      fibular transfer with vascular anastomoses. METHODS: Fourteen cases of forearm
      function dismissed due to defects of bone were managed by fibular transfer with
      vascular anastomoses. RESULTS: All cases obtained satisfactory effects, and
      recovered their normal function. CONCLUSION: The vascularized fibular transfer is
      a good method to reconstruct the forearm function with defects of bone resulting
      from injury or tumor.

PMID- 12212160
TI  - [Alterations of transforming growth factor beta 1 and p27kip1 mRNAs in gastric
      mucosa carcinogenesis].
AB  - OBJECTIVE: To investigate the effect of transforming growth factor beta 1 (TGF
      beta 1) and p27kip1 in gastric mucosa carcinogenesis. METHODS: RT-PCR was used to
      detect TGF beta 1 and p27kip1 mRNAs in normal gastric mucosa, simple hyperplasia,
      dysplasia and gastric carcinoma tissues respectively. RESULTS: There were
      expressions of TGF beta 1 and p27kip1 mRNAs in normal gastric mucosa, simple
      hyperplasia, dysplasia and gastric carcinoma tissues, the expressive levels of
      TGF beta 1 and p27kip1 mRNAs decreased gradually among the four groups. The
      expressive level of TGF beta 1 and p27kip1 mRNAs in gastric carcinoma group were
      significantly lower than those in other three groups(P < 0.05). CONCLUSIONS: The
      data indicate that TGF beta 1 and p27kip1 may play an important role in the
      development and carcinogenesis of gastric carcinoma. Semi-quantification PCR
      technique is effective for detecting mRNA expressive level in tissues.

PMID- 12212161
TI  - [The features and significance of immunophenotyping in adult acute leukemia].
AB  - Immunophenotypic assay was determined by using indirect immunofluorescent method
      in 120 adult patients with acute leukemia. Eight monoclonal CD antibodies
      consisting of anti-CD2, -CD7, -CD10, -CD19, -CD13, -CD33, -CD14, and anti-HLA-DR
      monoclonal antibodies were applied conventionally. The results were that
      immunophenotyping had high corresponding rate to FAB morphology typing in
      diagnosing acute leukemia. Also there were some patients who had cross or inverse
      CD marker expression or no specific CD antigen expression. There were some
      immunophenotypic features in AML-M3, ALL-L3, and B-Lineage and T-Lineage acute
      lymphocytic leukemia respectively. Prognostic significance was observed in the
      patients with specific immunophenotypes, that is acute myeloid leukemia patients
      with lymphoid antigen (Ly+ AML) and some cases with inverse immunophenotypes.

PMID- 12212162
TI  - [Relationship between the expression of bcl-2 apoptosis and acute myelogenous
      leukemia prognosis].
AB  - In order to check the anti-apoptosis gene bcl-2 protein expression in 58 AML
      patients we used the immunohistochemical method, and analyse the relationship
      between bcl-2 protein and prognosis of AML. The result showed that the high
      expression of bcl-2 protein was related to poor clinical prognosis of AML. This
      shows that the expression of bcl-2 gene can serve as an index for the prognosis
      of AML.

PMID- 12212163
TI  - [Changes of amino acids in cerebrospinal fluid of patients with cerebral
      infarction].
AB  - Using high performance liquid chromatography, we measured the Asp, Glu, Ser, Gly,
      Thr, Arg, Ala, Tyr, Met, Val, Phe, Ile, Ley, Lys, GABA concentrations in
      cerebrospinal fluid(CSF) of 15 patients with ischemic cerebral infarction and 10
      control subjects. The severity of the neurological deficit was assessed with
      Chinese stroke scale; infarct volume was determined by Zhang's method. The
      concentration of Asp, Glu, Ala, Leu were higher significantly in the infarct
      group than that in control(P < 0.01; P < 0.05); however, the concentration of
      GABA in the infarct group was lower than that in control(P < 0.05). The
      concentrations of Asp and Glu were positively correlated with infarct volume(rAsp
      = 0.56, P < 0.05; rGlu = 0.52, P < 0.05). The other amino acids were not
      correlated with infarct volume. All of the amino acids determined were not
      correlated with severity of neurological deficit. The results support the
      excitoxic activity of Asp and Glu in patients with ischemic cerebral infarction.
      Whether GABA protects neuronal tissue from ischemic cerebral damage needs to be
      studied further.

PMID- 12212164
TI  - [Study of parturient-controlled epidural blockade for labor analgesia].
AB  - To explore the feasibility of parturient-controlled epidural blockade for labor
      analgesia, 44 primiparas requesting labor analgesia (Group I) were selected for
      testing the above method according to the ASA (American Society of
      Anesthesiology) Class I or II. Forty-six primiparas were selected as control
      (Group II). The conditions of control group were similar to those of Group I in
      all aspects except labor analgesia. The results showed that in Group I labor pain
      was significantly relieved 5 minutes after anesthesia, and almost eliminated 15
      minutes after anesthesia; 95% parturients achieved adequate analgesia. Systolic
      pressure, diastolic pressure, heart rate and respiratory rate were significantly
      decreased 5 minutes after anesthesia but still in normal range. The uterine
      contraction, labor process, delivery mode, postpartum hemorrhage, side effects
      and neonatal Apgar's score had no significant difference between the two groups.
      It is suggested that the parturient-controlled epidural blockade is efficiently
      applied to labor analgesia.

PMID- 12212165
TI  - [The treatment of severe complications of laparoscopic cholecystectomy].
AB  - The treatment of 24 cases of severe complications of laparoscopic cholecystectomy
      (LC) in 1993-1998 is reported. Among them, 16 cases were from the other
      hospitals. The patients included 14 cases of bile duct injury, 3 cases of bile
      leak, 1 case of duodenal injury, 5 cases intraoperative hemorrhages, 1 case
      mediastinal emphysema. The data showed that bile duct injury was the most severe
      complication of LC. It is suggested that in order to prevent the complications a
      training of operators on adaptive exercise and standard intraoperative procedure
      should be undertaken. The diagnosis and treatment of severe complications are
      discussed and some useful advice is given in this paper.

PMID- 12212166
TI  - [Changes of endothelium-dependent and endothelium-independent dilatation of
      brachial arteries in patients with coronary heart disease].
AB  - By using high resolution ultrasound, the dilatation changes of brachial arteries
      during reactive hyperemia and after sublingual administration of glyceryl
      trinitrate(GTN) were measured in 99 subjects, consisted of 33 controls and 66
      patients with established coronary heart disease. The results showed that both
      flow-mediated dilatation(FMD) and GTN-induced dilatation of brachial arteries in
      patients with coronary heart disease were significantly reduced as compared with
      those in control group(2.44% +/- 2.94% vs 8.17% +/- 4.80% and 16.58% +/- 6.26% vs
      23.12% +/- 8.88%, respectively, P < 0.01 for all). Multiple linear stepwise
      regression analysis showed that FMD was positively related to high-density
      lipoprotein cholesterol and inversely related to baseline diameters of brachial
      arteries, age and low-density lipoprotein cholesterol, whereas GTN induced
      dilatation was positively related to FMD and inversely related to baseline
      diameters of brachial arteries. The present study suggests that both endothelium
      dependent and endothelium-independent vasodilatation are impaired in patients
      with coronary heart disease.

PMID- 12212167
TI  - [Investigation of trace elements in hair of patients with prostate carcinoma,
      benign prostatic hypertrophy, and normal controls].
AB  - Five trace metals (Cd, Cu, Fe, Mn, and Zn) in the hair of healthy subjects(n =
      10) and patients with benign prostatic hypertrophy (n = 17) and prostatic cancer
      (n = 18) were determined using atomic absorption spectrophotometry. The results
      were that zinc level in patients with prostatic carcinoma [(79.1 +/- 37.3)
      microgram.g-1] was significantly lower than that in patients with benign
      prostatic hypertrophy [(129 +/- 26.7) microgram.g-1] and normal controls [(152 +/
      31.5) microgram.g-1] (All P < 0.01); Cd, Cu, Fe, and Mn levels in the hair
      showed no statistic difference among the three groups (P > 0.05). It is suggested
      that the low zinc level in the hair might provide an important clue for
      diagnosing prostatic carcinoma at the early stage.

PMID- 12212168
TI  - [Study of plasma neuron-specific enolase activity of patients with chronic
      pulmonary heart disease complicated by pulmonary encephalopathy].
AB  - The plasma neuron-specific enolase (NSE) activity in the 15 patients of chronic
      pulmonary heart disease complicated by pulmonary encephalopathy and 10 chronic
      pulmonary heart disease without pulmonary encephalopathy (controls) were
      detected. The results showed that NSE activity in patients with moderate, severe
      pulmonary encephalopathy were significantly higher than those of patients with
      mild pulmonary encephalopathy, stable patients and controls. The plasma NSE
      activity from the patients with pulmonary encephalopathy were negatively
      correlated with the PaO2 and were positively correlated with PaCO2. This study
      suggests that plasma NSE activity may reflect the degree of brain damage by
      chronic hypoxia and remain of CO2 in the patients with chronic pulmonary heart
      disease.

PMID- 12212169
TI  - [Severe side effects of the treatment of acute promyelocytic leukemia with all
      trans retinoic acid].
AB  - Sixty-three cases with acute promyelocytic leukemia (APL) were treated with all
      trans retinoic acid (ATRA). The rates of hyperleukocytosis, intracranial
      hypertension, retinoic acid syndrome were 57.1%, 9.5%, and 3.2% respectively.
      Mortality of the treatment was 11.1%. Under ATRA treatment, hyperleukocytosis
      leading to leukostasis was the cause of death in patients with APL. We therefore
      suggest that the patients with such leukocyte levels (that is, 5.0 x 10(9).L-1 on
      the 6th day, 10.0 x 10(9).L-1 on the 10th day, 15.0 x 10(9).L-1 on the 15th day)
      can be used as guidelines for starting chemotherapy(homoharringtonine); before
      ATRA treatment, while leukocyte counts are > 10 x 10(9).L-1, the patients only
      receive homoharringtonine; when leukocyte counts are < or = 5.0 x 10(9).L-1, the
      patients receive a combination of homoharringtonine and ATRA. Retinoic acid
      syndrome is a distinctive complication of ATRA therapy in the patients with APL.
      While the syndrome occurs, the treatment of ATRA must be stopped and
      corticosteroids must be used.

PMID- 12212170
TI  - [Analysis of prognosis of severe hepatitis].
AB  - OBJECTIVE: To study the effect of prognosis of severe hepatitis. METHODS: The
      prognosis factors of 286 patients with severe hepatitis were studied with
      monofactor analysis(chi 2 test, t test) and polyfactors analysis(logistic
      regressive analysis). RESULTS: The factors affected the prognosis of the patients
      were age, therapeutics, biochemistry data and complications. CONCLUSION: To
      decrease the mortality of the patients with severe hepatitis, we should adopt
      rational therapeutics and prevent complications in clinical practice.

PMID- 12212171
TI  - [Evaluation of organ function monitoring and supporting during the treatment of
      multiple trauma].
AB  - OBJECTIVE: To analyse the evaluation of organ function monitoring and supporting
      during the treatment of multiple trauma. METHODS: Eighty-eight patients with
      severe multiple trauma were admitted into Department of Intensive Care Unit(ICU)
      and the cardiovascular, respiratory, renal, and coagulation functions, milieu
      interieur, and infectious sources were monitored. RESULTS: Seventy-six cases
      survived and twelve cases died. The major delayed diagnoses included pneumothorax
      hematopneumothorax, intraperitoneal organ injury, and fracture. The major
      complications were severe infection, hypotension, acute renal failure, adult
      respiratory distress syndrome (ARDS), and multiple organ disfunction
      syndrome(MODS). CONCLUSION: Active monitor and support of organ function can
      lower the rate of missed or delayed diagnoses and also decrease complications.

PMID- 12212172
TI  - [Functional repairing of complete type of epispadias: report of 2 cases].

PMID- 12212173
TI  - [Measurement of the inferior vena cava diameter for estimating fluid status in
      hemodialysis patients].
AB  - OBJECTIVE: To investigate the clinical application of inferior vena cava diameter
      (VCD) for estimating fluid status. METHODS: VCD were measured during the
      expiratory phase (VCD-E) in 64 patients before hemodialysis (hypervolemia) and 71
      normovolemia cases by ultrasonography, meanwhile collapsibility index (CI) were
      calculated. RESULTS: (1) VCD-E was (10.69 +/- 2.18) mm, CI was (26.24 +/- 6.34)%
      in normovolemic group; and (13.78 +/- 2.95) mm, (19.28 +/- 6.24%) in hypervolemic
      group respectively. There were significant differences in both (P < 0.01). (2)
      Change of VCD-E between pre- and post-dialysis was related with the amount of
      ultrafiltration during hemodialysis (r = 0.38, P < 0.01). The ratio was (2.0 +/-
      1.2) mm.kg-1. (3) By using VCD-E to estimate hypervolemia, receiver operating
      characteristic (ROC) curve showed if VCD-E > or = 13.0 mm, the sensitivity was
      87.0% and the specificity was 87.5%. CONCLUSION: VCD-E in postdialysis patients
      would approach (10.7 +/- 2.2) mm, which could be interpreted as being close to
      the dry weight. Thus VCD appears to be a valuable tool in estimating fluid
      status.

PMID- 12212174
TI  - [High-performance liquid chromatography determination of histamine in nasal
      mucosa of guinea pig after post-column derivatization].
AB  - A rapid and simple method for determining histamine by post-column derivatization
      liquid chromatography with fluorescent detection was described. SCX weakly acidic
      cation exchange column was used as an analytical column. Histamine was eluted at
      13 min 12 s by 40 mmol.L-1 of trisodium citrate (pH5.50) at flow rate of 1.0
      ml.min-1. The recoveries of histamine ranged from 1.0 mumol.L-1 to 100 mumol.L-1
      were above 92%. The detection limit for histamine was 50 nmol.L-1 and the linear
      range for histamine was 50 nmol.L(-1)-500 mumol.L-1.

PMID- 12212175
TI  - [Evaluation of susceptibility of tupaia to hepatitis B virus with cyclosporin A].

PMID- 12212176
TI  - [Influence of over-weight and obesity on blood pressure, blood sugar, lipid and
      uric acid in elderly people].

PMID- 12212177
TI  - [Long-term follow-up of mitomycin C in trabeculectomy].

PMID- 12212178
TI  - [Study of intracranial hypertension from traumatic brain edema treated with
      eliminating the stagnant and catharsis with a small dose mannitol].

PMID- 12212179
TI  - [Pathogen analysis of urogenital infection in Hunan Province of China].

PMID- 12212180
TI  - [Measurements of IL-6 and TNF-alpha in tuberculosis and malignant effusion].

PMID- 12212181
TI  - [Squamous cell carcinoma of renal pelvis].

PMID- 12212182
TI  - [Study of plasma endothelin and calcitonin gene related peptide in patients with
      heart failure].

PMID- 12212183
TI  - [Clinical analysis of 134 cases of herpes zoster].

PMID- 12212184
TI  - [Autologous epidermal grafting plus sicorten cream in the treatment of vitiligo].

PMID- 12212185
TI  - [Restoration of cervical wedge-shaped defect of teeth using sandwich technique of
      light cure composite and glass ionomer cement].

PMID- 12212186
TI  - [Clinical analysis of drug-induced demyelinating encephalopathy].

PMID- 12212188
TI  - [A case of pulmonary blastoma metastasized to the heart].

PMID- 12212187
TI  - [Comparative study on the efficacy of KLH-IDT and SEA-IDT in diagnosing
      schistosomiasis japonica].
AB  - Thirty-three egg-positive subjects and 32 egg-negative subjects were tested
      synchronously by KLH-IDT and SEA-IDT in endemic area of schistosomiasis. Compared
      with stool examination, the positive coincidence rate of KLH-IDT and SEA-IDT were
      90% and 100%, respectively, which showed no statistical significance(P > 0.05),
      and the negative coincidence rate of KLH-IDT and SEA-IDT were 71.9% and 25%,
      respectively, which showed statistical significance(P < 0.01). Of the 31 egg
      negative subjects, 9 subjects showed positive by both SEA-IDT and KLH-IDT, and 15
      subjects showed positive by SEA-IDT but negative by KLH-IDT. Both double positive
      subjects and single positive subjects were examined further by miracidium
      hatching test, there were 2 subjects showing positive among the 9 double positive
      subjects. In addition, of 27 subjects that had been treated one year before, only
      6 subjects showed positive by KLH-IDT, the reversion rate was 77.8%; whereas, the
      reversion rate was 22.2% (6/21) by SEA-IDT. The results suggest that KLH-IDT has
      high value in diagnosing schistosomiasis, particularly shows a potential in
      assessing therapeutic efficacy of schistosomiasis.

PMID- 12212189
TI  - [Expression and purification of recombinant Schistosoma japonicum paramyosin].
AB  - Paramyosin of Schistosoma japonicum was expressed at a high level in E. coli. The
      recombinant protein could be easily purified from bacteria lysate by fast protein
      liquid chromatography(FLPC) on a TALON resin column, due to the protein being
      expressed with a tag of six histidine residue fused to the N-terminus. The
      protein was completely soluble and could be eluted under non-denaturing condition
      using imidazole. To eliminate imidazole and residue of E. coli, the elution was
      further purified by ion-exchange chromatography. The purified protein will be
      used in water buffaloes in the study on protective immunity against Schistosoma
      japonicum.

PMID- 12212190
TI  - [Protective effects of baicalin, mannitol and dexamethasone on infective brain
      edema in rats].
AB  - OBJECTIVE: To compare the therapeutic effects of baicalin, mannitol and
      dexamethasone on infective brain edema(IBE) in rats. METHODS: Forty normal
      Sprague-Dawley(SD) rats (200 +/- 30) g by weight were divided into 5 groups
      randomly: (1) normal saline control group(NS, n = 8); (2) infective brain edema
      group (BE, n = 8); (3) mannitol treatment group(MAN, n = 8); (4) dexamethasone
      treatment group(DXM, n = 8); and (5) baicalin treatment group(BC, n = 8).
      Pertussis bacilli(PB, contained bacilli in 10.8 x 10(9), 0.2 ml-1.kg-1) were
      injected into the left carotid arteries through the left common carotid arteries
      by puncture to obtain BE models. The contents of brain water, sodium ion,
      potassium ion and Evans blue in brain tissues were observed too. RESULTS: The
      contents of brain water, sodium ion, and EB in BE group were higher than those in
      BE group(P < 0.01), they decreased in MAN, DXM, BC groups and were lower than
      those in BE group(P < 0.01). In MAN, DXM, BC groups, there were no significant
      difference in the contents of brain water and sodium ion(P > 0.05). The EB
      content in BC group was higher than that in MAN and DXM groups(P < 0.01). The
      content of potassium ion in BE group was higher than that in MAN and DXM groups,
      the content of potassium ion was similar to that in NS group, but lower than that
      in BC group. Light microscope inspection in MAN, DXM and BC groups showed
      lessened brain edema, slight increase of perivascular space, and occasional nerve
      cell pyknotic nucleus. We found on nerve cell vacuolar degeneration in DXM group.
      CONCLUSION: Baicalin, mannitol and dexamethasone all have similar protective
      effects on infective brain edema in rats.

PMID- 12212191
TI  - [Five-case report of Bartter syndrome].

PMID- 12212192
TI  - [Intravenous infection of C. albicans induces apoptosis of cortical thymocytes in
      mice].
AB  - In this study, we aimed to understand the location of apoptotic cells in murine
      thymus and phenotype of murine thymocytes involved in C. albicans induced
      apoptosis. Results showed that significant increase of apoptotic cells in thymus
      began at 6 h after intravenous injection of C. albicans and kept increased at 12
      h, 18 h and 24 h. Quantitative changes of thymocytes with different phenotype
      measured by flow cytometry revealed that percentage of CD3+ and CD8+ cells were
      significantly reduced compared to the controls. Moreover in situ cell death
      detection of thymic tissue revealed that apoptotic cells induced by C. albicans
      mainly located in the thymic cortex, while in the thymic medulla a very small
      number of thymocytes was involved. Taken together our study indicates that C.
      albicans induces apoptosis of murine thymocytes, moreover the apoptosis possibly
      involves the major immature CD3+ CD4+ CD8+ cells in the thymic cortex and minor
      mature CD3+ CD4- CD8+ cells in the thymic medulla.

PMID- 12212193
TI  - [Spectrophotometric determination of copper in the hair of the patients with
      rheumatoid arthritis].
AB  - A new color reaction of copper (II) with solochrome cyanine R was studied by
      spectrophotometry. The results were that in the pH6 of HAc-NaAc buffer solution
      solochrome cyanine R reacted with copper (II) to form a violet complex; the
      maximum absorption of the complex was at 565 nm and its apparent molar absorption
      coefficient was 8.25 x 10(5) L.mol-1.cm-1. Beer's Law was obeyed in the range of
      0-0.48 microgram.ml-1. This method was used to determine copper levels in the
      hair samples of 5 normal persons and 5 rheumatoid arthritis patients. The results
      showed that the hair copper level of arthritis patients was significantly higher
      than that of normal persons (P < 0.01).

PMID- 12212194
TI  - [Preliminary report on immunoscreening of Schistosoma japonicum adult worm cDNA
      library by sera from infected Microtus fortis].
AB  - Microtus fortis (Mf) is resistant to Schistosoma japonicum (Sj) infection. To
      explore if Mf responses to special Sj antigens after infection, Sj adult worm
      cDNA library was screened with sera from infected Mf. Twelve positive clones were
      obtained after rescreening. After automatically excised with the helper phage,
      positive clones were further identified by PCR. The size of Sj cDNA fragments in
      positive clones ranged from 300 bp to 1.8 kb. Six of these fragments were 300 bp,
      one was 1 kb, and five were 1.8 kb in size. The results indicate that the
      infected Mf serum could recognize Sj specific antigens. It is valuable to further
      study the immune protection of these cloned molecules.

PMID- 12212195
TI  - [Protective effect of perindopril on dysfunction of endothelium-dependent
      relaxation in diabetic rats].
AB  - To investigate the effect of Perindopril, an angiotensin converting enzyme(ACE)
      inhibitor, on dysfunction of ECs-dependent relaxation in diabetic rats induced by
      streptozotocin(STZ) at different times, acetylcholine(Ach)-induced ECs-dependent
      relaxation of rat aortic rings was tested, and the concentrations of plasma
      glucose and AngII were measured. The results showed that: 1. Four weeks later
      after injecting STZ, the function of ECs-dependent relaxation was not injured in
      diabetic control group(DC), but the concentrations of plasma glucose and AngII
      were increased significantly compared with normal control group(NC). The Ach
      induced relaxation was declined obviously compared with NC at 8 or 16 weeks after
      injecting STZ. 2. treatment with Perindopril significantly protected the function
      of ECs-dependent relaxation, the Ach-induced relaxation was obviously increased
      compared with DC. The concentration of plasma glucose was not changed, but the
      plasma AngII was reduced compared with DC. CONCLUSION: Perindopril could protect
      the function of ECs-dependent relaxation in diabetic rats.

PMID- 12212196
TI  - [Chemically induced (streptozotocin-alloxan) diabetes mellitus in dogs].
AB  - To evaluate the efficiency and toxic and side effect of the combined chemical
      inducer for Type I diabetes mellitus, Type I diabetes in 9 adult dogs were
      induced with alloxan(50 mg.kg-1) and streptozotocin (30 mg.kg-1) with vein
      injection. After 7-14 days, the blood glucose of 5 male dogs was kept on high
      levels [mean value was (22.7 +/- 3.2) mmol.L-1], exogenous insulin was (21.4 +/-
      2.4) U.day-1. Three female dogs died in 7 days after they had been injected with
      the combined inducers. Alloxan-streptozotocin combination administration reduced
      the dosage of each drug, and decreased the toxic and side effect of each drug.
      The results suggest that this method has a high rate of success to induce Type I
      diabetes male dogs.

PMID- 12212197
TI  - [Effects of Buyang huanwu decoction on the release of vWF and the expression of
      tissue factor induced by tumor necrosis factor alpha in cultured bovine aortic
      endothelial cells].
AB  - OBJECTIVE: To study the effects of Buyang huanwu decoction (BHD) on the release
      of von Willebrand factor(vWF) and the expression of tissue factor(TF) activity
      induced by tumor necrosis factor alpha (TNF alpha) in cultured bovine aortic
      endothelial cells (BAECs). METHODS: BAECs from neonatal cox were cultured and 4-8
      passages were used. Cells were incubated for 8 hours after addition of different
      treatments. The supernatant was used to measure vWF and BAECs lysate to determine
      TF activity. RESULTS: 1. Compared with the control, TNF alpha enhanced the
      expression of TF activity(12.79 +/- 2.59 vs. 4.69 +/- 0.83, P < 0.01) and the
      effects were in dose-dependent manner(r = 0.9712, P < 0.01); BHD inhibited the
      effects of TNF alpha(P < 0.01). 2. Compared with the control, TNF alpha promoted
      the release of vWF from endothelial cells (13.28 +/- 4.76 vs. 6.42 +/- 2.84, P <
      0.01) and BHD inhibited the effect of TNF alpha(P < 0.01). CONCLUSION: BHD can
      inhibit the expression of TF and the release of vWF induced by TNF alpha.

PMID- 12212199
TI  - [Influence of lead on activity of nitric oxide synthase in neurons and vessel
      smooth muscle of small intestine in rats].
AB  - The beta-NADPH histochemical method was used to study the effect of lead on
      activity of nitric oxide synthase(NOS) in neurons and vessel smooth muscles of
      intestinal wall in rats. The results showed that the number of NOS positive
      neurons and fibers was decreased and degenerative changes of some NOS positive
      neurons were found after the lead acetate intraperitoneal injection. The activity
      of NOS in the vessel smooth muscles was reduced. It suggests that lead colic may
      be induced by reduction of NO in the neurons which innervate the gut smooth
      muscles.

PMID- 12212198
TI  - [Relationship between vascular endothelial growth factor expression and
      microvessel density in hepatocellular carcinomas and their surrounding liver
      tissue].
AB  - The relationship between vascular endothelial growth factor (VEGF) expression and
      microvessel density was studied with immunohistochemical method in hepatocellular
      carcinoma (HCC) and pericarcinomatous liver tissue. The positive rate of VEGF in
      HCCs was significantly lower than in surrounding liver tissues (66.7% vs. 85.4%,
      P < 0.05). There was no significant difference between HCC and pericarcinomatous
      liver tissue on expressive intensity of VEGF. The positive signal of VEGF was
      mainly localized in cytoplasma of cancer cells, pericarcinomatous hepatocytes,
      and vascular endothelial cells. The microvessel density in HCC was higher than in
      pericarcinomatous liver tissue and closely correlated to differentiated degree of
      cancer cells (rs = 0.5870; rs = 0.8235). The poorer cancer cell differentiation,
      the higher microvessel density. The results suggest that VEGF may not be the sole
      factor that stimulates angiogenesis in HCC genesis and development. To detect
      microvessel density in judging prognosis and biological behavior of HCC is more
      important than that of VEGF.

PMID- 12212200
TI  - [Experimental study of tendon allograft].
AB  - A series of immunologic tests, including lymphocyte cell toxicity test, as well
      as lymphocyte transformation test, macrophage function test, histological
      examination, and biomechanical measurement were carried out in guinea pigs to
      compare the effect of deep freezing(Group I) with deep freeze drying(Group II) on
      tendon allografts. The results revealed that the lymphocyte mortality,
      lymphocytic-transformed rate and phagocytizing rate of the macrophages in Group I
      and Group II were lower than those in non-processed allograft group (Group III)
      and had no statistical difference among Group I, Group II and Group III. As
      compared with the non-processed allograft, the freezed and freeze-dried
      allografts showed ameliorated immunologic reactions, mild morphological lesion
      and better mechanical strength after transplantation. The results suggest that
      deep freezing and deep freeze-drying processing are valid measures in tendon
      allograft treatment.

PMID- 12212201
TI  - [Allelic polymorphism of HLA-DQA1 locus in Han nationality in Hunan province].
AB  - OBJECTIVE: To explore the genetic polymorphism of HLA-DQA1 locus in Han
      nationality in Hunan province. METHOD: Sixty samples randomly selected from
      healthy individuals of Han nationality in Hunan province were typed for HLA-DQA1
      by PCR/SSP in combination with silver-staining PCR/SSCP. RESULTS: Ten types of
      HLA-DQA1 alleles were found in all 60 samples, HLA-DQA1*0302, *0501, *0102 were
      the common alleles with gene frequencies of 0.2254, 0.2254, and 0.2041
      respectively. Twenty-six kinds of genotypes were found, and the genotype
      distribution fitted the Hardy-Weinberg equilibrium test (P > 0.05). Five samples
      which had ambiguity in their PCR/SSP typing were further clarified with PCR/SSCP
      analysis. CONCLUSIONS: Normal gene frequency values of HLA-DQA1 alleles in Han
      nationality in Hunan province are provided; PCR/SSCP can be used to eliminate the
      ambiguity which might exist in PCR/SSP typing for HLA-DQA1 locus.

PMID- 12212202
TI  - [Research on mental health status of 726 adolescents and its influential
      factors].
AB  - Mental health status of 726 adolescents and their backgrounds were investigated
      with Symptom Check List(SCL-90) and self-designed questionnaire. The results
      showed that the prevalence rate of psychological problems ranged from 6.34% to
      24.93%. Among these problems, obsession led all the others. Females had higher
      scores in interpersonal sensitivity, depression, anxiety, phobia than males.
      Logistic regression analysis indicated that the major factors contributed to
      mental health status of adolescents were the relationship between teacher and
      student, father's concern with his child, only child or not, parents'
      expectations, personality and sex. The study provides reference source for
      improving the mental health status of adolescents.

PMID- 12212203
TI  - [Study on the etiology of herpes viral encephalitis in Changsha area].
AB  - OBJECTIVE: To study the relationship between herpes viral infection and viral
      encephalitis. METHODS: The cerebral spinal fluid(CSF) and sera of the patients
      with viral encephalitis were detected for herpes virus-specific IgG and IgM with
      indirect fluorescent antibody assay (IFA). RESULTS: One hundred and thirty-three
      (14.4%) cases of 921 patients with viral encephalitis were diagnosed as herpes
      simplex viral encephalitis, of which the maximum morbidity is under the age of
      10, 9(0.98%) cases as cytomegaloviral encephalitis and 12 (1.3%) cases as
      varicella-zoster viral encephalitis. CONCLUSION: Herpes simplex viruses are the
      common causative agents of viral encephalitis in Changsha area, and IFA is
      valuable for the diagnosis of herpes viral encephalitis.

PMID- 12212204
TI  - [Analysis of dynamic blood pressure of essential hypertension patients with
      Ganyang shangkangzheng or Gan-shengyinxuzheng].
AB  - Inspecting twenty-four hours dynamic blood pressure of sixty-two essential
      hypertension patients with Ganyang shangkangzheng or Gan-shengyinxuzheng in
      normal conditions and analysing blood pressure's dynamic regularity of the two
      groups with different traditional Chinese medicine Zheng type, we found that the
      blood pressure of Ganyang shangkangzheng patients was higher in the daytime than
      that at night, and the Gan-Shengyinxuzheng patients had the reverse results. The
      results suggest that the dynamic blood pressure value may be an objective index
      for differential diagnosis of traditional Chinese medicine Zheng types of
      patients with essential hypertension.

PMID- 12212205
TI  - [Investigation of the effects of biotic field of plant seedling on human body].
AB  - In this paper we investigated the effects on human bodies after being placed in
      the Jiang's guideti cabin with biotic field to receive the plant seedlings'
      irradiating biological electromagnetic waves. The results found that the
      erythrocyte membrane permeability and fragidity were decreased, its tenacity
      increased, the secretion of thyroid and sexual hormones increased, the immune
      function enhanced and there was no significant alteration of the adrenal cortical
      hormone secretion. It is suggested that the electromagnetic wave from the plant
      seedlings is beneficial to the erythrocyte function, improves the metabolism,
      enhances the adolescent activities, improves sexual activity and enhances immune
      function, thus it is effective to health care and rejuvenation.

PMID- 12212206
TI  - [Effects on simvastatin in continuous ambulatory peritoneal dialysis patients
      with hyperlipidemia].
AB  - The therapeutic effects of simvastatin on hyperlipidemia and its protective
      effects on residual renal function (RRF) in continuous ambulatory peritoneal
      dialysis (CAPD) patients with hyperlipidemia were observed. Forty-seven CAPD
      patients were randomly divided into two groups, the treatment group and control
      group. The treatments of two groups were the same except that the treatment group
      patients were additionally given simvastatin 20 mg.d-1. The results were that,
      after 12-week treatment, the total cholesterol (TC), triglyceride (TG), low
      density lipoprotein (LDL), and apoprotein B100 (ApoB100) in the treatment group
      significantly decreased, but high density lipoprotein (HDL) and apoprotein A1
      (ApoA1) significantly increased compared with the control group (all P < 0.05);
      one year later, RRF of patients of both groups all decreased but there was no
      significant difference between them. The results suggest that simvastatin can
      effectively normalize lipidemia, but has no protective effect on RRF in CAPD
      patients.

PMID- 12212207
TI  - [Graft of AAA bone combined with autologous red bone marrow for treatment of bone
      defects].
AB  - To evaluate the effect of autolyzed antigen-extracted allogenic bone ("AAA" bone)
      graft combined with autogenic red bone marrow on bone defects, 58 cases with
      benign bone tumor(66 long bones) were treated with curettage operation, and the
      post-curettage bone defects were filled with the complex of "AAA" bone combined
      with autogenic red bone marrow. Forty two cases(49 bones) were followed up by
      taking X-ray radiography every 2 months in a period of 1-3 years. The result
      showed that 49 bones all got bony healing within 9 months(6 months in average).
      It is suggested that "AAA" bone combined with autogenic red bone marrow may be an
      ideal material for bone defect repairing.

PMID- 12212208
TI  - [Extracorporeal shock wave lithotripsy for renal calculi].
AB  - OBJECTIVE: The aim of the study was to determine the effectiveness of
      extracorporeal shock wave lithotripsy(ESWL) therapy for renal calculi. METHODS:
      126 patients were treated with Shanghai HX-902 lithotriptor on an inpatient
      basis. The stone size varied from 0.5 to 2.5 cm. Some patients had a double-J
      stent inserted prior to treatment. RESULTS: The overall stone-free rate in 2
      months was 45.6%, whereas it was 53.3%, 40.8% and 18.1% according to the stone
      size, < or = 0.8, 0.9-1.9 and > or = 2 cm, respectively. Complications were rare,
      including 1 subcapsular hematoma formation, 15 renal colics and 5 stone streets,
      which were managed by conservative treatment or ureteral stenting or additional
      ESWL and resulted in complete stone clearance. CONCLUSION: ESWL therapy is a
      reasonable and effective method for renal stone, percutaneous
      nephrolithotripsy(PCNL) or open surgery should be considered for stones larger
      than 2 cm.

PMID- 12212209
TI  - [Effect of peritoneal dialysis in elderly patients].
AB  - OBJECTIVE: To evaluate the effects of peritoneal dialysis in elderly patients.
      METHOD: One hundred and fifty-five patients were divided into two groups(elder
      aged group > or = 60 years, 59 cases; medium aged group < 60 years, 96 cases).
      The changes of blood pressure, Hb and renal function between the two groups were
      compared after six months of peritoneal dialysis. The data were processed by SPSS
      7.0 software. RESULTS: Primary disease analysis showed 47.4% hypertension and
      28.8% diabetes in elder-aged group and 72.9% chronic glomerulonephritis in medium
      aged group. The changes of Bp and Hb was not significant in both groups after
      dialysis. Renal function was improved in both groups. Concentration of total
      protein and albumin was decreased in elder-aged group and remained nearly
      unchanged in medium-aged group after dialysis. The survival rates of the two
      groups had no difference. CONCLUSION: As a simple, safe and effective method,
      peritoneal dialysis is especially suitable to elderly patients for continuous
      treatment.

PMID- 12212210
TI  - [Relationship between insulin resistance and clustering of risk factors of
      cerebrovascular disease].
AB  - OBJECTIVE: To study the relationship between insulin resistance and clustering of
      risk factors of cerebrovascular disease. METHODS: The serum concentrations of
      fasting glucose, insulin, lipids, the activities of tissue-type plasminogen
      activator (t-PA) and plasminogen activator inhibitor-1(PAI-1), and the level of
      blood pressure were measured in 159 patients with stroke and 40 healthy control
      subjects. RESULTS: All subjects were divided into 4 groups in the light of number
      of risk factors of cerebrovascular disease. As the number of risk factors
      increased, the insulin sensitivity index (ISI) in four groups gradually
      decreased. The ISI in the patients with cerebrovascular disease was negatively
      associated with increased levels of SBP, DBP, TG, APOB, and PAI-1 activity (P <
      0.01) and positively with decreased level of HDL (P < 0.01). CONCLUSION: Insulin
      resistance is associated with clustering of risk factors of cerebrovascular
      disease, the more resistant, the more clustered.

PMID- 12212211
TI  - [Effects of aprotinin on TNF-alpha levels after cardiopulmonary bypass].
AB  - OBJECTIVE: This study evaluates the anti-inflammatory activity of full-dose and
      pump-prime-only(low-dose) aprotinin by means of comparing tumor necrosis factor
      alpha(TNF-alpha) levels of both groups after CPB. METHODS: Twenty-nine adults
      with rheumatic heart disease were randomized into three groups: (1) full-dose
      aprotinin-treated group(Group A, n = 10); (2) pump-prime-only aprotinin-treated
      group(Group B, n = 10), and (3) control group(Group C, n = 9). Plasma
      concentrations of TNF-alpha were measured by enzyme-linked immunosorbent assay
      technique at baseline(before operation), and at 2, 24 hours after CPB
      termination. RESULTS: A significant(P < 0.05) increase of TNF-alpha occurred in
      all three groups at 2 and 24 hours after CPB termination when compared with the
      same group at baseline. In Group A, TNF-alpha level was significantly lower than
      that in group C(P < 0.05) at 24 hours after CPB, but not in group B(P > 0.05).
      CONCLUSIONS: Both CPB and operative stimulus induce the increase of cytokine TNF
      alpha after CPB. Full-dose aprotinin has the anti-inflammatory effect by means of
      reducing TNF-alpha level after CPB. Low-dose aprotinin dose not reduce TNF-alpha
      level. So it no significant anti-inflammatory effect.

PMID- 12212212
TI  - [Arthroscopic meniscus plasty of the discoid cartilage of the knee joint].
AB  - From 1989 to 1998, arthroscopic discoid lateral meniscus plasty was performed in
      twenty-eight patients(thirty-one joints), and evaluated in a short follow-up
      term. The mean age was 21.5(6-42) years. The average follow-up period lasted 8.4
      months. The results were assessed by the Ikeuchi's grading, 87.1% joints had
      excellent and good results, including all incomplete types and 77.8% complete
      type of discoid meniscus. It is suggested that arthroscopic meniscus plasty plays
      an important role in the treatment of discoid meniscus of knee, and should be
      performed possibly as soon as the disease was diagnosed by arthroscopic
      examination.

PMID- 12212213
TI  - [Clinical significance of P-glycoprotein and CD34 expression of acute leukemia].
AB  - The expression of P-glycoprotein(P-170) and CD34 was detected in the bone marrow
      mononuclear cells of 30 patients with acute leukemia by immunocytochemical
      technique using JSB-1 and Tuk 3 monoclonal antibody. The results were that
      expression of P-170 and CD34 had no significant difference between acute
      nonlymphoblastic leukemia and acute lymphoblastic leukemia(P > 0.05). The
      clinical therapeutic effect was poor in P-170 or CD34 positive patients and had
      significant difference compared with those negative patients(P < 0.05). Judgments
      of therapeutic effect for acute leukemia can be improved by detecting the
      expression of P-170 and CD34 simultaneously.

PMID- 12212214
TI  - [Comparative study of pulmonary magnetic resonance angiography (MRA)].
AB  - Imaging was performed using a 1.0 Tesla superconducting MR system with a body
      coil. Two-dimensional(2D) turbo FLASH sequence and/or three-dimensional(3D) FISP
      sequence were carried out in 46 volunteers with 113 pulmonary MRA. The total MRAs
      were divided into 4 groups and analysed. The results showed: After Gd-DTPA was
      injected, the signal-to-noise ratio(SNR) of pulmonary 2D- and 3D-TOF MRA was
      increased in 46 normal pulmonary MR angiography cases(P < 0.01); the number of
      left and right pulmonary artery divisions identified was much greater than that
      before Gd-DTPA injection both in 2D- and 3D-MOF(except lingual segment of left
      lobe). It is suggested that Gd-DTPA may markedly promote the efficiency of
      pulmonary MRA.

PMID- 12212215
TI  - [Effect of puerarin on heart function and serum oxidized-LDL in the patients with
      chronic cardiac failure].
AB  - OBJECTIVE: To observe the effect of puerarin on heart function and serum oxidized
      LDL(ox-LDL) in patients with chronic cardiac failure. METHODS: Seventy-eight
      patients with chronic cardiac failure were randomly divided into two groups,
      regular group (R) and regular + puerarin group (P). All patients in two groups
      received conventional treatment with inotropic agents, diuretic, and vasodilator,
      etc. The patients in the P group took puerarin 400 mg.d-1 for 10 days. RESULTS:
      After treatment, the clinical heart function of the patients in the two groups
      was improved, but there was no significant difference between them; the left
      ventricular ejection fraction (EF) of patients in the P group was higher than
      that in the R group(P < 0.05); and serum ox-LDL level was significantly decreased
      in the P group patients, but that was no change in the R group patients(P <
      0.05). CONCLUSION: Puerarin may improve the clinical heart function, increase the
      left ventricular ejection, meanwhile, it may decrease the level of ox-LDL.

PMID- 12212216
TI  - [Myelopathy-hand and cervical spondylotic myelopathy].
AB  - The clinical manifestations and MRI characteristics of 58 patients with cervical
      spondylotic myelopathy were analysed in this study. The results showed that there
      was myelopathy-hand in 49 patients and none in 9 patients. Two groups were not
      significantly different in gender, age, course and involved segment, side or
      level of spinal cord(P > 0.05), but were significantly different in the
      compression degree of spinal cord(P < 0.01). In the positive group, the degree of
      myelopathy-hand was positively related to the severity of spastic gait, pyramidal
      tract sign and spinal cord compression.

PMID- 12212217
TI  - [Effect of propofol and propofol combined with ketamine on cardiovascular
      system].
AB  - OBJECTIVE: To prevent blood pressure from reducing caused by injection of
      propofol. METHODS: Thirty patients, ASA Grade I-II, were randomly allocated into
      one of the two groups: Group I (Group P, n = 15) and Group II (Group K + P, n =
      15), the patients received 2 mg.kg-1 propofol in Group I and 1 mg.kg-1 ketamine
      before equal dose of propofol in Group II. Systolic blood pressure(SBP),
      diastolic blood pressure(DBP), mean blood pressure and heart rate were measured
      before injection and 1 min, 3 min, 5 min and 10 min respectively after injection.
      RESULTS: Blood pressure in Group I was significantly lower than Group II.
      CONCLUSION: Ketamine can attenuate the hemodynamic responses to propofol.

PMID- 12212219
TI  - [Effects of rhGM-CSF and rhG-CSF on growth of CFU-F derived from acute leukemia
      (AL) patient bone marrow in vitro].
AB  - By using the cultural method of CFU-F derived from bone marrow in the patient
      with acute leukemia in vitro, we dissected the effects of rhGM-CSF and rhG-CSF on
      growth of CFU-F derived from AL patient bone marrow. The results showed that rhGM
      CSF and rhG-CSF enhanced the number of colonies of CFU-F and its proliferation
      activity. Both factors had a synergy on the above effects. The effects of rhGM
      CSF on CFU-F were significantly greater than that of rhG-CSF. The data indicate
      that rhGM-CSF and rhG-CSF might regulate hemopoiesis more effectively by
      stimulating the growth of fibroblast and improving bone marrow microenvironment.

PMID- 12212218
TI  - [Research of compound cyclosporin A mouthwash in the treatment of oral lichen
      planus].
AB  - Thirty patients of oral lichen planus(OLP) were treated with compound CyA
      mouthwash, while the control group was treated with KouTai. The results showed
      that the rate of success and total rate of success of patients treated with
      compound CyA mouthwash were 63 percent and 97 percent respectively, but those of
      the control group treated with kouTai were 10 percent and 63 percent
      respectively. There was a statistically significant difference(P < 0.01). No side
      effects were found. The mouthwash is an effective, safe and local drug used in
      the treatment of OLP.

PMID- 12212220
TI  - [Expressions and their clinical significance of bcl-2 and nm23 in epithelial
      ovarian carcinoma].
AB  - The expressions of bcl-2 and nm23 protein in epithelial ovarian carcinoma were
      analyzed by immunohistochemical method. The results were that 1. the positive
      expression of bcl-2 protein was 60% (27/45) in epithelial carcinoma; the positive
      expression of bcl-2 protein in Grade I was 31.25% (5/16), in Grade II 57.14%
      (8/14), in Grade III 93.33% (14/15) and there were significant differences among
      them (P < 0.05); 2. the positive expression of nm23 protein was 40% (18/45) in
      epithelial carcinoma; the positive expression of bcl-2 protein in Stage I/II was
      57.1% (12/21), in Stage III/IV 25% (6/24), and there was significant difference
      between them (P < 0.05). We conclude that the expressions of bcl-2 and nm23
      protein are associated with tumor differentiation and clinical stage
      respectively. Analyzing the expressions of bcl-2 and nm23 are beneficial to the
      prognosis of the ovarian tumor patients.

PMID- 12212222
TI  - [Study of the fluid-percussion graded model of experimental brain injury in
      rats].
AB  - OBJECTIVE: To study the histopathological aspects of the fluid-percussion graded
      model of experimental brain injury in rats and the relationship between the fluid
      percussion graded model and the clinical grades of brain injury. METHODS: The
      graded model of rats was set up by using the device of the improved fluid
      percussion model, then we observed the changes of brain tissue of rats. RESULTS:
      The fluid-percussion graded model of experimental brain injury could be
      pathologically graded. CONCLUSION: The pathological grade of the fluid-percussion
      graded model can be used to evaluate the degree of brain injury in clinic and in
      experiments.

PMID- 12212221
TI  - [Effect of thrombin on cell proliferation and plasminogen activator inhibitor
      type (PAI-1) expression in human embryonic glomerular mesangial cells].
AB  - OBJECTIVE: To explore the effect of thrombin on cell proliferation and
      plasminogen-activator inhibitor Type 1(PAI-1) expression in human embryonic
      glomerular mesangial cells. METHODS: Methyl-tetragolium (MTT) incorporation,
      fibrin plate assay and Northern blotting hybridization were used to examine the
      mesangial cells proliferation, protein activity and mRNA expression of PAI-1 in
      cultured human embryonic mesangial cells induced by thrombin, respectively.
      RESULTS: Thrombin enhanced glomerular mesangial cell proliferation, PAI-1 protein
      activity and mRNA expression in a dose-dependent manner, which could be blocked
      by hirudin, a specific inhibitor of thrombin. CONCLUSION: Thrombin could enhance
      mesangial cell proliferation, and up-regulate protein activity and mRNA
      expression of PAI-1 in cultured human embryonic glomerular mesangial cells. It
      may play an important role in the pathogenesis of glomerulosclerosis induced by
      thrombin.

PMID- 12212223
TI  - [Clinical analysis of 29 cases of hounglass spinal tumor].
AB  - We analysed retrospectively 29 cases with hounglass tumor in spinal canal from
      March 1990 to November 1998 in our hospital. Hounglass tumors in all patients
      were successfully diagnosed by CT scanning and magnetic resonance imaging(MRI).
      Microsurgery was carried out in 27 cases(27/29). Sixteen out of 27 cases were
      followed up from 8 months to 7 years. The result showed that 12 cases got
      complete healing, and 3 cases incomplete healing. The paper has stress discussion
      on the clinical features, CT, MRI examination and operation of the disease.

PMID- 12212224
TI  - [Oral submucous fibrosis complicated with lichen planus disease].

PMID- 12212225
TI  - [Effects of serum-free murine bone marrow endothelial cell conditioned medium on
      the growth of CFU-E and BFU-E].
AB  - Serum-free murine bone marrow endothelial cell conditioned medium(mBMEC-cm) was
      collected. The mBMEC-cm was ultrafiltered in Centriprep. The concentrated
      retentive substance of mBMEC-cm (MW > 10,000) and filtrate of mBMEC-cm(MW <
      10,000) were obtained. The effects of mBMEC-cm on the growth of CFU-E and BFU-E
      were investigated. The results showed: 1. The retentive substance of mBMEC-cm
      significantly enhanced the growth of CFU-E and BFU-E. The effects of mBMEC-cm(2%
      6%, V/V) on the growth of CFU-E and BFU-E were dose-dependent. 2. The filtrate of
      mBMEC-cm markedly inhibited the growth of CFU-E and BFU-E. The effects of the
      filtrate of mBMEC-cm on the growth of CFU-E and BFU-E were also dose-dependent.
      The mechanism of regulation will be studied further.

PMID- 12212227
TI  - [Effect of prolonging time for sampling on preservation of ultrastructure during
      the specimen preparation].
AB  - The ultrastructural change of rat liver, which was not immediately fixed after
      separation from the animal, was observed under electron microscope. The results
      showed that the ultrastructure of hepatocytes still satisfied the needs for
      diagnostic electron microscopy if the isolated livers were soaked in normal
      saline for 30 minutes, at room temperature, or placed in 4 degrees C refrigerator
      for 60 minutes, then they were fixed. After the isolated samples were put at room
      temperature for over 30 minutes, ultrastructure of hepatocytes were damaged so
      severely as to lose value for observation under electron microscope.

PMID- 12212226
TI  - [Detection of GLO I phenotypes in blood and blood stains using agarose starch gel
      electrophoretic analysis].
AB  - The distribution of GLO I phenotypes was studied using mixed agarose starch gel
      electrophoresis in 234 Chinese Han population in Changsha area. Three GLO I
      phenotypes were detected. The gene frequencies were as follows: GLO I1 = 0.1303
      and GLO I2 = 0.8697. The phenotype frequencies of GLO I were compared not only
      among the different nationalities but with those reported by other countries.
      Both the 20 bloodstain samples kept at room temperature for 40 days and the other
      20 bloodstain samples kept at 4 degrees C for at least 100 days could be
      correctly phenotyped. Two out of 8 watered bloodstains, their GLO I2-1 phenotype
      was changed to GLO I2-2. In blind trial, 15 bloodstain samples kept at room
      temperature for 40 days could be phenotyped correctly.

PMID- 12212228
TI  - [Effect of an improved rice soup culture medium on Candida albicans forming
      chlamydospore].
AB  - Three types of culture medium that stimulated Candida albicans to form
      chlamydospore were compared with the improved rice soup culture medium. The
      results were that the effect of the improved rice soup culture medium on
      stimulating C. albicans to form chlamydospore was better than the effects of
      others; a large number of chlamydospores could be gotten in 18 h. The results
      indicate that this method, the improved rice soup culture medium, is easy,
      simple, and economic. A method for making the teaching slide of C. albicans
      forming chlamydospore was also introduced.

PMID- 12212229
TI  - [Rapid high performance liquid chromatography for determination of phenylalanine
      and tyrosine in serum].
AB  - OBJECTIVE: To develop a rapid assay for the determination of phenylalanine and
      tyrosine in serum. METHODS: The serum sample was injected directly into High
      performance liquid chromatography(HPLC) system after precipitation of protein
      with perchloric acid, and monitored at 190 nm with an ultraviolet detector.
      RESULTS: Good linearity was observed in 6-1,512 mumol.L-1 range for
      phenylalanine, the intra-run and inter-run imprecisions(CV) were 3.68% and 4.01%,
      the recovery rate was 98.6%; good linearity was observed in 5.4-1,380.0 mumol.L-1
      range for tyrosine, the intra-run and inter-run imprecisions were 1.87% and
      2.59%, the average recovery rate was 98.9%. CONCLUSION: This method is simple,
      rapid, sensitive, accurate, and suitable for clinical application.

PMID- 12212230
TI  - [Bone mineral density characteristics at the femoral neck and Ward's triangle for
      Chinese women].
AB  - The incidence of hip fracture is not as high in Chinese women compared to women
      from Western countries, though they usually have low bone mineral density(BMD)
      and get osteopenia easily. In this study, reference data(white women) supplied by
      the manufacturer of Hologic was compared with data obtained from healthy women in
      Changsha, Hunan, P.R.C. One thousand four hundred and eighty-eight Chinese women
      aged 15 to 95 years were randomly recruited. Measurements of BMD were taken at
      the hip by the dual energy x-ray absorptiometry(QDR 4,500A, Hologic Inc., USA).
      The BMD was somewhat lower than reference curves at all ages and all sites. But
      at the femoral neck and Ward's triangle, Chinese women reached their peak BMD 5
      to 10 years later than the reference group, and had a lower BMD rate of decrease
      for about 35 years after peak BMD was reached. Whether the differences(i.e.,
      longer time to peak BMD and a lower BMD decrease rate at the neck and Ward's
      triangle after the peak BMD reached) will result in a protection from hip
      fractures for Chinese women needs to be studied in the future.

PMID- 12212231
TI  - [Expression of interleukin-5 and interleukin-10 and their relationship in
      asthma].
AB  - To explore the expression of interleukin-5(IL-5) and interleukin-10(IL-10) and
      their relationship in asthma, we measured the cells in bronchial alveolar lavage
      fluid(BALF) of guinea pigs, and examined the expression of IL-5 mRNA and IL-10
      mRNA of bronchial tissue by reverse transcription polymerase chain reaction(RT
      PCR) in control group(Group C, n = 10), asthmatic group(Group A, n = 11) and
      dexamethasone treatment group(Group B, n = 10). The results showed that the
      eosinophil(EOS) percentage and the expression of IL-5 mRNA were significantly
      higher in Group A[(48.64 +/- 17.8)%, (106.91 +/- 20.09)% respectively] than that
      in Group C[(15.10 +/- 11.48)%, (62.60 +/- 13.84)%] and Group B[(28.4 +/- 10.32)%,
      (75.30 +/- 10.70)%]. In contrast, the IL-10 mRNA expression in Group A[(47.5 +/-
      5.3)%] was obviously lower compared with that in Group C[(101.2 +/- 4.2)%] and
      Group B[(80.1 +/- 8.3)%]. The correlation between the expression level of IL-5
      mRNA and percentage of EOS was positive(r = 0.924, P < 0.01), whereas the IL-5
      mRNA was negatively correlated with IL-10 mRNA expression(r = -0.731, P < 0.01).
      CONCLUSION: IL-5 and EOS might play a role in the pathogenesis of asthma, the
      inhibition of IL-10 mRNA expression may cause the increase of IL-5 expression in
      asthma. The beneficial effects of corticosteroid treatment in asthma may partly
      result from increasing IL-10 mRNA expression and inhibiting IL-5 mRNA expression.

PMID- 12212232
TI  - [The negative effect of 4-methylhistamine, an H2 receptor agonist, on
      cytotoxicity of Ara-C for HL-60 leukemia cells].
AB  - OBJECTIVE: To study the effect of 4-methylhistamine on cytotoxicity of Ara-C for
      HL-60 leukemia cells in vitro. METHODS: Proliferation of HL-60 cells was
      determined by semi-solid colony culture and 3H-TdR incorporation. The typical NBT
      reduction was used to check cell differentiation. Intracellular cAMP and calcium
      concentration were determined by high pressure liquid chromatography(HPLC) and
      fluorescence method, respectively. RESULTS: When HL-60 cells were pretreated with
      10(-8) mol.L-1 4-MH for 24 hrs, the cytotoxicity of Ara-C[10(-8)-10(-4)mol.L-1]
      for HL-60 leukemia cells was significantly decreased both in liquid and semisolid
      culture. The result of colony counting indicated that the IC50 for HL-60 cells
      were 1.68 x 10(-6)mol.L-1 with 4-MH pretreatment nad 2.14 x 10(-8)mol.L-1 without
      4-MH pretreatment, respectively. Therefore, the potency of Ara-C was reduced
      nearly 80 times according to IC50 doses. It is interesting that 10(-6)mol.L-1
      ranitidine, an antagonist of H2 receptor, can elaborate the negative effect of 4
      MH on cytotoxicity of Ara-C for HL-60 cells. CONCLUSION: The dose of Ara-C should
      be adequately increased, or Ara-C should be used with H2 receptor antagonist such
      as ranitidine when treating myeloid leukemia patients.

PMID- 12212233
TI  - [Effect of a novel aminosteroid on animal model of murine myelomonocytic
      leukemia].
AB  - To evaluate the effect of a novel aminosteroid on murine myelomonocytic leukemia,
      BALB/c mice were treated by the novel aminosteroid for 7 days after receiving 1 x
      10(6) WEHI-3B(myelomonocytic leukemia) cells intraperitoneally. The counts and
      classification of white blood cells obtained from tail blood were determined on
      the day before transplanting WEHI-3B cells and 7, 14, 21, 28 days after
      transplantation. Undifferentiated cell percentage of bone marrow and spleen
      weight were checked 30 days after transplantation. The results demonstrated that
      the above indexes of mice treated with the novel aminosteroid were decreased
      compared with those treated with normal saline(NS). Decrease of the indexes
      showed a dose-dependent relationship ranging from 5-20 mg.kg-1.d-1. It is
      suggested that leukemia mice could be effectively treated by the novel
      aminosteroid and the efficacy maybe paralleled with the dosage of the novel
      aminosteroid.

PMID- 12212234
TI  - [Correlative study on HLA-DR2 allelic polymorphism and systemic lupus
      erythematosus in the Han nationality in Hunan province].
AB  - Fifty-eight systemic lupus erythematosus (SLE) patients and 59 normal controls of
      the Han nationality in Hunan province were involved in this study to analyze the
      correlation between HLA-DR2 group specific amplification in combination with HLA
      DRB generic amplification PCR/SSCP technique to detect the sequence variation
      within exon 2 of HLA-DR2 alleles outside the sequence specific primer matching
      positions. The results were that HLA-DR2 was strongly correlated with SLE (RR =
      2.71, P < 0.01); and HLA-DRB1 * 1501 was the allele correlated with disease (RR =
      3.01, Pc < 0.05). In addition, PCR/SSCP showed that there was not any novel
      sequence variation in exon 2 of HLA-DR2 alleles in the Han nationality in Hunan
      province.

PMID- 12212235
TI  - [MDM2 gene amplification and overexpression in nasopharyngeal carcinoma].
AB  - MDM2 gene amplification and overexpression were detected by DNA dot blot analysis
      and reverse transcription-polymerase chain reaction (RT-PCR) in 32 cases of
      nasopharyngeal carcinoma (NPC), 10 cases of chronic inflammation of
      nasopharyngeal epithelium(CINE) and NPC cell line HONE1. One case of NPC showed
      MDM2 gene amplification, NPC cell line HONE1 and ten cases of NPC showed MDM2
      mRNA overexpression. No MDM2 gene amplification and overexpression were found in
      CINE. MDM2 mRNA overexpression was significantly related to cervical lymph node
      metastasis, but not to T stage of NPC. The results indicate that MDM2 gene may
      play an important role in the pathogenesis and the process of metastasis of NPC.

PMID- 12212236
TI  - [Kenacort-A treatment in children with refractory nephrotic syndrome].

PMID- 12212237
TI  - [Study on the optimum experimental conditions for the steady growth of human K
      562 cell line].
AB  - The results of the assays of growth state, semisolid colony culture,
      cytomorphological and chromosome analysis for K-562 cell line showed that the
      cells had the similar biological characteristics with the cells which were
      originally established. It suggests that the growth state of K-562 cells under
      the experimental conditions in our laboratory are steady.

PMID- 12212238
TI  - [Effects of different loading exercises on endogenous sex hormones and their
      metabolites].
AB  - Small loading and strengthening exercises were performed by 22 athletes(11 males
      and 11 females). The levels of serum hormones and their urinary metabolites were
      detected. The results showed that the serum levels of testosterone(T), free
      testosterone(FT) and 17-OH-progesterone(17-OHP) in male athletes exhibited no
      conspicuous changes. The excretion of their urinary androsteroids was
      significantly increased after exercises(P < 0.05), but significantly decreased in
      the recovery period(P < 0.05). After small loading exercises, their serum levels
      of T and FT revealed no obvious changes except those of 17-OHP which evidently
      increased in female athletes(P < 0.05); whereas the excretion of their urinary
      steroid hormones declined promptly after the exercises and in the recovery period
      (all P < 0.05). After strengthening exercises, the serum levels of T, FT and 17
      OHP decreased distinctly in female athletes (all P < 0.05), the excretion of
      their urinary steroid hormones raised clearly after training and in the recovery
      period(P < 0.05). Therefore, it is suggested that the secretion and metabolism of
      sex hormones in the organism are influenced by the loading quality of sports
      during training, and sexual difference exists simultaneously.

PMID- 12212240
TI  - [Present-conditions of nutritional knowledge of clinical doctors].
AB  - Nutritional knowledge of 184 clinical doctors was investigated by questionnaires.
      The results showed that clinical doctors did not have enough nutritional
      knowledge to meet the demands of their work. The doctors grasped fundamental
      nutritional knowledge better than clinical nutritional knowledge (P < 0.01).
      There was no significant difference between the doctors in different groups with
      different academic degrees, professional titles, work histories, and departments
      (P > 0.05). Therefore, we suggest that the class hours of nutrition science can
      be added, the course of clinical nutrition can be offered in medical university,
      and the nutritional knowledge of clinical doctors can be improved by conducting
      nutritional science training course.

PMID- 12212239
TI  - [Study on trace elements in epithelial cells during oral carcinogenesis prevented
      by garlic].
AB  - Sixty-two Wistar rats were divided randomly into two groups, thirty-one for each
      group. The posterior hard palatal mucosae of all animals were painted thrice
      weekly with 0.5% 4-nitroquinoline 1-oxide(dissolved in dimethyl sulfoxide).
      Before that, the garlic injection solution and the distilled water were painted
      at the same place of the experimental and control group animals, respectively.
      All animals were killed in turn from the beginning of the experiment at random at
      the 10th, 13th, and 19th week. Then, trace elements of intranuclear and cytoplasm
      of epithelial cells or cancer cells at the mentioned weeks were surveyed by
      electron probe microanalysis. The results were that garlic decreased the levels
      of intranuclear and cytoplasm copper(P < 0.05); the levels of intranuclear and
      cytoplasm selenium at the 10th week and the 13th week(P < 0.05) and those of zinc
      at the 19th week (P < 0.01) increased. So, garlic inhibits oral carcinogenesis by
      changing concentrations of intranuclear and cytoplasm trace elements that is
      copper, zinc, selenium, and the ratio of the three elements.

PMID- 12212241
TI  - ["Bu-yang huanwu tang" inhibited the pathogentic process of atherosclerosis
      induced by cholesterol-rich diet in rabbits].
AB  - BACKGROUND AND OBJECTIVE: "Bu-yang huanwu tang", a decoction of Chinese herbs
      widely used in the treatment for cardio- and cerebro-vascular diseases, has been
      demonstrated to be able to inhibit platelet adhesion and aggregation, to lower
      blood lipids, to regulate vascular tone from animal experiments. The aim of this
      study is to determine whether this decoction inhibits the pathogentic process of
      atherosclerosis induced by cholesterol-rich diet in rabbits. METHODS: Three
      groups of rabbits received the following different diets for 9 weeks: 1. standard
      diet; 2. atherogenic diet(standard diet plus 1% cholesterol and 3.3% fat); 3.
      atherogenic diet plus this decoction(5 g.kg-1.d-1). Plasma lipids, 6-keto-PGF1
      alpha, endothelin levels were detected and the histological atherosclerotic
      changes were evaluated. RESULTS: This decoction inhibited the progression of
      aortic and abdominal aortic intimal plaques and reduced aortic intimal
      thickening. CONCLUSION: The anti-atherogenic mechanism might be related to the
      decrease of plasma cholesterol and triglycerides and the increase of PGI2. The
      facts suggest that "Bu-yang huanwu tang" has antiatherogenic and antithrombotic
      effects.

PMID- 12212242
TI  - [Frequency of prothrombin gene G20210A variant in the 3'-untranslated region in
      Chinese people with ischemic stroke].
AB  - OBJECTIVE: To ascertain the frequency of prothrombin(F II) gene 3'-untranslated
      region(3'-UT) G20210A variant and to explore whether this mutation is related to
      arterial thrombosis in Chinese people. METHODS: We studied 49 patients with
      thrombosis and 46 healthy Chinese persons. The patients had a first ischemic
      stroke. The G20210A mutant allele of the prothrombin gene in all blood specimens
      was investigated by DNA extraction, polymerase chain reaction amplification, Hind
      III digestion and polyacrylamide gel electrophoresis (PAGE). RESULTS: The
      patients and normal control subjects were all homozygous for the normal G20210G
      allele, and there was no any F II G20210A variant. CONCLUSION: Factor II gene 3'
      UT G20210A mutant allele is absent in Chinese patients with ischemic stroke and
      normal subjects; its mutation may not be a major risk factor for thrombogenesis
      in Chinese people.

PMID- 12212243
TI  - [Detection of the soluble form of the Fas molecule in patients with multiple
      sclerosis].
AB  - We examined the levels of the soluble form of the Fas(sFas) in the cerebrospinal
      fluids(CSF) and the sera of patients with multiple sclerosis(MS) using an enzyme
      linked immunosorbent assay (ELISA). The levels of sera and CSF sFas were
      significantly higher in MS patients than that in other neurological diseases
      (OND) group and healthy control(HC); MS patients in the active stage had more
      sFas molecule than that in the inactive stage. It suggests that sera and CSF sFas
      may be related to clinical activity in patients with MS, and that sFas may play
      an important role in the pathogenesis of the MS.

PMID- 12212244
TI  - [Analysis of retinoic acid in subretinal fluid in patients with rhegmatogenous
      retinal detachment].
AB  - To investigate the relationship between the level of retinoic acid (RA) in the
      subretinal fluid (SRF) and the extent of the vitreoretinopathy in 56 patients
      with rhegmatogenous retinal detachment, we studied the levels of RA in both SRF
      and serum using high liquid chromatography and also examined those levels in part
      of patients who took oral vitamin A 150,000 U.d-1. The results were that the
      level of RA in the SRF increased with the grade of the proliferative
      vitreoretinopathy (PVR); the levels of RA in both SRF and serum were
      significantly higher in the cases with vitamin A than those without. We conclude
      that retinoic acid metabolism between retinal pigment epithelial cells and neural
      epithelia was unbalanced after retinal detachment. Oral vitamin A is helpful to
      inhibit the genesis and development of the proliferative vitreoretinopathy.

PMID- 12212245
TI  - [Therapeutic hemodynamic effects of external counterpulsation on elderly patients
      with brain infarction during convalescence].
AB  - The therapeutic hemodynamic effects of external counterpulsation(ECP) and medical
      routine therapy in elderly patients with brain infarction during convalescence
      were investigated by Transcranial Doppler (TCD). The results showed that
      hemodynamic parametres(Vp, Vm, DVp, DVm) and asymmetry of MCA in elderly patients
      with brain infarction who were treated with ECP have improved significantly(P <
      0.001), but that of MCA in elderly patients with brain infarction who were
      treated with medical routine therapy have not significantly improved. Therapeutic
      hemodynamic effects of ECP on elderly patients with brain infarction were much
      better than that of medical routine therapy(P < 0.001).

PMID- 12212246
TI  - [Clinical significance of calcitonin expression in lung tissue with
      bronchiectasis].
AB  - OBJECTIVE: To investigate the relation between the pathologic feature of
      bronchiectasis and the expression of calcitonin(CT) protein within pulmonary
      neuroendocrine cells(PNEC) in bronchiectasis. METHOD: CT expression of PNEC was
      detected using immunohistochemistry(SP method) and quantitative analysis was
      completed by counting CT positive cell number on per 10 cm length of epithelium.
      RESULT: CT positive PNEC were found both at all levels of airway tree in all 37
      cases of bronchiectasis and 10 cases of control, but none were found in alveolar
      ducts and alveoli. In bronchiectasis, CT positive PNEC was 67.59 +/- 10.57 per 10
      cm length of epithelium, and in control group 5.48 +/- 1.06. Statistical analysis
      revealed a significant difference between bronchiectasis and control(P < 0.001).
      CONCLUSION: There was a high level CT expression in bronchiectasis. The PNEC
      hyperplasia may play a role in the chronic inflammation of bronchiectasis.

PMID- 12212247
TI  - [Analysis of complication in the spinal pedicle screw internal fixation].
AB  - In 1990-1998, five hundred and twenty patients treated with spinal pedicle screw
      internal fixation were analyzed. The main operative complication was screw
      misplacement(7.1%), and others such as screw bend and extra-long screw were less
      seen. The postoperative complications included screw breakage (13.3%) and
      backache(14.2%). Recently, by making use of RF screw system and X-ray monitor,
      the complications were significantly decreased.

PMID- 12212248
TI  - [Low volume mechanical ventilation in the treatment of patients with chronic
      obstructive lung diseases with type II respiratory failure].
AB  - To study the value of low volume ventilation in chronic obstructive lung disease
      (COPD) with Type II respiratory failure, 35 patients were divided into two groups
      at random. The tidal volume of regular volume ventilation group was 12-14 ml.kg-1
      and that of low volume ventilation group was 6-8 ml.kg-1. Some indexes of airway
      pressures and blood gases were recorded and those of cardiovascular function were
      monitored continuously. The results were that compared to the normal volume
      ventilation group, the actual ventilation in liters per minute was lower
      obviously, the expiratory time longer, the incidence rate of lung barotrauma
      lower, peak inspiratory pressure, end-inspiratory-pressure, and internal positive
      end-expiratory pressure smaller, and side-effect on hemodynamics less in the low
      volume group. The results suggest that low volume ventilation with permissive
      hypercapnia is better than normal volume ventilation in COPD.

PMID- 12212249
TI  - [A morphometric study on the microvessel in oral submucous fibrosis].
AB  - To investigate the pathologic change of the microvessel in oral submucous
      fibrosis(OSF), the pathologic buccal tissues of 27 patients with OSF were studied
      by using immunochemical method. Microvessel quantity(MVQ), quantity density(QD),
      microvessel area(MVA) and area density(AD) were determined by means of computer
      aided image analysis system. The results showed the increase in MVQ and QD in the
      early stage and the decrease in MVQ, QD, MVA and AD in the middle stage and the
      late stage. The authors concluded that presence of microvessel hyperplasia
      occurred in the early stage of OSF.

PMID- 12212250
TI  - [Ultrasonic diagnostic value of endometrium cancer].

PMID- 12212251
TI  - [Electrocardiographic QRS waves of healthy Chinese population with different ages
      and sexes].
AB  - OBJECTIVE: To develop a normal electrocardiographic QRS wave standard in Chinese
      population with different ages and sexes. METHODS: Fourteen leads
      electrocardiographic QRS waves of 4,322 Chinese healthy subjects aged from birth
      to 85 years old divided into 11 age-groups were analysed and studied. RESULTS:
      There were highly significant differences in QRS amplitudes and cardiac electric
      axes of different ages and sexes. The changes of QRS amplitudes which increased
      and decreased with advancing age were usually earlier in female than in male.
      Comparing with QRS waves there were higher QRS amplitudes in girls than in boys
      in the newborn period; however, it is higher in male than in female in puberty
      and middle-aged persons. The sex difference was not obvious relatively in small
      children and the aged. There was significant difference in QRS amplitudes when
      electrocardiograms of Chinese people compared with those of Westerners.
      CONCLUSION: A Chinese normal electrocardiographic QRS standard established
      according to different ages and sexes may be applied clinically.

PMID- 12212252
TI  - [The expression of p42/p44MAPK and cyclin D1 protein and their relationship in
      Hodgkin's disease].
AB  - The expressions of p42/44 mitogen-activated protein kinase(p42/p44MAPK) and
      cyclin D1 protein were detected by SP immunohistochemical technique in 40 cases
      of Hodgkin's disease(HD) and 13 cases of reactive hyperplasia(RH). The results
      showed that p42/p44MAPK and cyclin D1 protein were both overexpressed in RS/H
      cells of HD(positive rates were 72.5% and 70% respectively), and their positive
      rates were positively correlated(P < 0.01). The data suggest that MAPK cascades
      signal transduction may play an important role in genesis of HD. MAPK may induce
      overexpression of cyclin D1 protein and result in persistent proliferation and
      progression of RS/H cells.

PMID- 12212253
TI  - [Brainstem auditory evoked potentials (BAEPs) and assessment of personality test
      in patients with migraine].
AB  - OBJECTIVE: To explore personality test and brainstem auditory potentials (BAEPs)
      in patients with migraine. METHODS: BAEPs and eysenck personality scale were
      recorded in 30 patients with migraine. RESULTS: The abnormal rate of BAEPs was
      53%. The latency of individual wave I, III and V were prolonged, so did the
      interval of the wave III and wave V. The results of personality test showed that
      3 patients(10%) manifested introvert personality, 12 patients (40%) extravert
      personality, and 17 patients (56%) the intermediate personality. CONCLUSION: It
      is indicated that migraine may be related to the disturbance of brainstem
      disfunction and personality of patients.

PMID- 12212255
TI  - [A case report of large clear cell carcinoma of thyroid].

PMID- 12212256
TI  - [Surgical treatment for mitral valve prolapse].
AB  - OBJECTIVE: To determine the excellent operative procedure to treat mitral valve
      prolapse (MVP). METHODS: Fifty seven patients with MVP were divided into three
      groups: Group I received traditional chordal reconstruction; Group II underwent
      chordal replacement using expanded polytetrafluorethylene(e-PTFE) sutures and
      artificial ring valvuloplasty reconstruction; Group III submitted mitral valve
      replacement. RESULTS: Mitral regurgitation volume was reduced significantly in
      Group II [(1.3 +/- 3.8) ml] and Group III [(1.2 +/- 3.4) ml] than that in Group I
      [(4.7 +/- 7.7) ml] (P < 0.05). CONCLUSION: The utilization of e-PTFE sutures as
      artificial chordae and artificial ring valvuloplasty for MVP is a more reliable
      and safe procedure than traditional mitral valve reconstruction, and can avoid
      the complications of long term anticoagulant therapy after mechanical valve
      replacement.

PMID- 12212254
TI  - [Effect of propofol and midazolam on cerebral oxygen supply and demand imbalance
      during cardiopulmonary bypass].
AB  - Thirty patients undergoing heart valve replacement were divided randomly into
      three groups (n = 10): control group, propofol group and midazolam group. Jugular
      bulb blood oxygen saturation (SjO2), arterialvenous oxygen content difference (Da
      vO2) and cerebral oxygen extraction rate(CEO2) were measured at various periods
      of cardiopulmonary bypass (CPB). The results showed: SjO2 decreased
      significantly, Da-vO2 and CEO2 increased markedly during rewarming period in
      control group; but in propofol group and midazolam group, SjO2, CEO2 and Da-vO2
      did not decline significantly compared with baseline. It is suggested that
      administering propofol or midazolam is helpful in avoiding cerebral oxygen supply
      and demand imbalance during CPB.

PMID- 12212257
TI  - [Detection of D -dimer in pleural effusion].
AB  - The content of D -dimer in pleural fluid of different causes was examined by the
      ELISA method in 45 patients. The results were that the contents of D -dimer in
      both tuberculous and empyema pleural effusions were significantly higher than in
      malignant pleural effusion (P < 0.01; P < 0.05). D -dimer was positively
      correlated with lactic dehydrogenase (LDH) in pleural fluid (r = 0.4168, P <
      0.01). The results suggest that fibrinolytic activities in tuberculous and
      empyema pleural effusion are much higher than in malignant pleural effusion. The
      detection of D -dimer in pleural fluid may reflect the extent of pleural
      inflammation and be helpful in the differential diagnosis of pleural effusion.

PMID- 12212258
TI  - [Detection of apoptosis by in situ labeling and study on the expression of PCNA
      in hypertrophic scars and keloids].
AB  - To investigate the involvement of apoptosis and proliferation in the lesions of
      hypertrophic scars and keloids, eighteen samples of hypertrophic scar and five
      samples of keloid were collected. The apoptosis was detected with terminal
      deoxynucleatidyl transferase mediated d-UTP biotin nick end labeling(TUNEL) and
      the expression of PCNA was assessed with immunohistochemical technique in scar
      lesions and normal skin. Results showed that in hypertrophic scar and keloid
      samples the rate of proliferating cells in dermis was higher than that of normal
      skin(P < 0.05), whereas the apoptosis index between scars and normal skin shows
      no statistical significance. It indicates that excessive proliferation and the
      lack of apoptosis of cells in dermis may cause the formation and development of
      hypertrophic scars and keloids.

PMID- 12212259
TI  - [The relationship between bone mineral density and secondary hyperparathyroidism
      bone disease].
AB  - The bone mineral density (BMD) and Z score in distal 1/3 radius were measured
      with dual energy X-ray absorptiometry (DEXA) in 185 hemodialysis (HD) patients,
      meanwhile serum parathyroid hormone (PTH), alkaline phosphatase (ALP) and hand X
      rays were detected. Results showed that BMD in HD patients was significantly
      lower than that in control group(P < 0.05), and decreased with dialysis duration
      increasing. BMD in HD patients was negatively related with PTH, ALP and rate of
      subperiosteal erosions. By using Z score to diagnose hyperparathyroidism bone
      disease, receiver operating characteristic (ROC) curve was worked out. If Z score
      < or = -2.02, the sensitivity was 79.41% and specificity was 78.15%. In
      conclusion the measurement of BMD is a useful tool for the detection of
      hyperparathyroid bone disease.

PMID- 12212260
TI  - [Prognostic effect of angina before acute myocardial infarction in elderly
      patients].
AB  - OBJECTIVE: The present study examined whether angina 48 h before acute myocardial
      infarction provided protection in early and adult patients. To investigate the
      effect of ischemic preconditioning in senescent heart. METHODS: We
      retrospectively verified whether antecedent angina within 48 h myocardial
      infarction exerted a beneficial effect on in-hospital outcomes in adult(< 60
      years old, n = 68) and elderly (> or = 60 years old, n = 118) patients. RESULTS:
      In-hospital congestive heart failure was more frequent in adult patients without
      than in those with previous angina(16.7% vs 2.6%, P < 0.05), as were cardiogenic
      shock and death(23.3% vs 5. 3%, P < 0.05) and the combined end points(in-hospital
      congestive heart failure and shock or death) (40.0% vs 7.9%, P < 0.01). In
      contrast, the presence or absence of previous angina before acute myocardial
      infarction in elderly patients seemed to have no obvious influence, the incidence
      of in-hospital congestive heart failure(17.7% vs 20.0%, P > 0.05), shock and
      death(23.5% vs 20.3%, P > 0.05) and combined end points(41.2% vs 40.0%, P >
      0.05). But the elderly patients with angina showed a significantly smaller
      infarct size compared with elderly patients without angina, the long-term
      cardiogenic death was more frequent in elderly patients without than in those
      with previous angina(18.0% vs 5.9%, P < 0.05). CONCLUSIONS: The presence of
      angina before acute myocardial infarction seems to confer significant protection
      against in-hospital outcomes in adults; this effect seems to be present in
      elderly patients. This study suggests that the protection afforded by angina in
      adult and elderly patients may involve the occurrence of ischemic
      preconditioning.

PMID- 12212261
TI  - [Intraoperative application of acute normovolemic hemodilution].
AB  - To investigate the effects of acute normovolemic hemo-dilution(ANHD) on
      hemodynamics and hemobiochemistry during surgery. In 30 patients(ASA Grade I-III)
      undergoing selective surgery, ANHD was accomplished by exchanging whole blood(8.0
      +/- 2.7) ml.kg-1 with an equal volume of gelofusine after induction of
      anesthesia. The results showed: after ANHD, Hb, Hct and Plc levels respectively
      decreased by 13.8%(P < 0.05), 17.1%(P < 0.05) and 7.1%(P > 0.05), and yet kept in
      normal range; MAP, HR, SpO2, ECG maintained the normal level; and no significant
      changes were observed in the concentration of Na+, K+ and Cl-. ANHD is a safe and
      effective technique of autotransfusion, and can decrease or avoid the risk of
      disease transmission.

PMID- 12212262
TI  - [An improved deresining method for semithin sections embedded-epoxy resin].
AB  - Deresining must be performed for HE, specific histochemical staining and
      immunohistochemical detection on semithin-sections embedded-epoxy resin. The
      deresining process in general methods had to take 24 hours, and the semithin
      sections were easily separated from slides. An improved method was introduced in
      this paper, by which deresining time was only 5 minutes, and it could also avoid
      the separation of semithin-sections from the slides. The staining result was very
      good, and the resolving power of images was high.

PMID- 12212263
TI  - [Derivative-ratio derivative spectrum method for determining nitrate and nitrite
      radicals (NO3- and NO2-) in environmental water].
AB  - A derivative-ratio derivative spectrum method was devised for resolving the
      interference of two components in a two-component mixture measured in derivative
      spectrum method. The ratio derivative spectrum was obtained from the derivative
      absorption spectrum of the mixture divided by a derivative absorption spectrum of
      one of the components. The derivative of ratio derivative spectrum against
      wavelength resulted in the derivative-ratio derivative spectrum that was
      determined by the concentration of one component of the mixture. The results
      suggest that this method is better than ratio derivative spectrum method and it
      can be applied for determining nitrate and nitrite (NO3- and NO2-) in environment
      water samples. Being simple and stable, it can eliminate the influence of the
      interfering materials, giving a recovery rate of more than 96.7%.

PMID- 12212264
TI  - [Screening of all types of alleles of (A-C)n dinucleotide tandem repeat sequence
      of aldose reductase gene].
AB  - The screening method of seven alleles (Z-6, Z-4, Z-2, Z, Z + 2, Z + 4 and Z + 6)
      in the (A-C)n dinucleotide tandem repeat sequence was studied. These alleles
      constitute a microsatellite DNA marker upstream of the transcription initiation
      site on the aldose reductase gene. At first, genoimic DNAs were isolated from
      leucocyte pellets, and the region containing the dinucleotide repeats was
      amplified by PCR with a pair of amplification primers that flanked 132-144 bp
      region. Then, the PCR products of the DNA samples whose alleles belonged to
      homozygotes were selected, purified, and sequenced directly in order to find out
      the types of alleles. Finally, using Z-2 allele as a marker, the samples
      containing Z-2 allele were detected by 12% fromamide-urea gel electrophoresis
      together with silver-staining. This method is simple, quick and accurate. It
      facilitates the screening of a large number of samples and is also suitable for
      identification of other dinucleotide tandem repeat sequences.

PMID- 12212265
TI  - [An improved method of preparative techniques for electron microscopic
      examination in renal biopsy].

PMID- 12212266
TI  - [Determination of urinary endothelin-1 and nitric oxide in patients with
      different pathologic types of primary glomerulonephritis].

PMID- 12212267
TI  - [Ergometrine provocative test for diagnosing variant angina pectoris].

PMID- 12212268
TI  - [Preliminary study on establishing the technique of human embryo reconstruction].

PMID- 12212269
TI  - [Effects of insulin on synthesis and secretion of apolipoproteins A I, A II,
      B100, C III and E by cultured HepG2 cells].
AB  - This study was intended to observe the effects of insulin on synthesis and
      secretion of apolipoproteins by hepatic cells. The HepG2 cells were cultured in
      RPMI 1640 media with bovine insulin (1 microgram/ml media and 10 micrograms/ml
      media) for 72 hours, and the apolipoproteins contents in cultured media were
      measured by radioimmunodiffusion assay (RID) kits developed by authors' research
      laboratory. 40 fold lyophilizely condensed culture media were used for the
      assays. The results showed that the relative amounts of apo A I, A II, B100, C
      III and E secreted by HepG2 cells detected by this method were 824 +/- 27, 813 +/
      24, 4875 +/- 82, 597 +/- 74 and 97 +/- 4 ng/mg cell protein, respectively. When
      1.0 microgram/ml medium of bovine insulin was added into the culture media, apo A
      I and apo E secretion remained unchanged. When compared with the control, while
      apo A II tended to decrease, apo C III tended to increase, and apo B100 secretion
      decreased by 21.2%; when 10.0 micrograms/ml medium of insulin was added, apo A I,
      A II and B100 secretion decreased by 6.9% (P < 0.05), 44.3% (P < 0.01) and 29.3%
      (P < 0.01) respectively, while apo C III secretion increased by 51.8% (P < 0.01).
      These results support certain parts of the hypothesis of pathogenesis of Chinese
      endogenous hypertriglyceridemia proposed by Bing-Wen Liu.

PMID- 12212271
TI  - [Study of the immunological tolerance induced by peripheral intravenous infusion
      of donor-specific antigens].
AB  - In the experiment, donor specific tolerance was induced by DST, DSSL and DSBM
      through peripheral intravenous transfusion in rat cervical cardiac
      transplantation model. The results showed there were significant differences in
      graft survival time between the blank control group and the other groups (P <
      0.05). The mean graft survival time days of the DST, DSSL and DSBM groups were
      28.9 +/- 13.7, 42.9 +/- 6.6 and 40.3 +/- 11.6 days, respectively. The effect of
      component infusion was obviously better than that of DST (P < 0.05), but no
      statistical difference was observed between DSSL and DSBM. CsA gave a noticeable
      synergistic effect to the induction of immunological tolerance. MLR and CD8+ T
      cell were remarkably reduced(P < 0.05) in the cases of component transfusion.
      This study suggested that components transfusion may be of clinical use for donor
      specific tolerance inducing.

PMID- 12212272
TI  - [Sub-cloning and preliminary sequence analysis of the gene encoding of a
      cefoperazone hydrolyzing beta-lactamase isolated from Escherichia coli].
AB  - Escherichia coli HX88108, which is resistant to cefoperazone(CPZ), was isolated
      from a severely infected patient. We studied genetical basis of beta-lactamase
      produced in E. coli HX88108 by pFL25, one of the recombinant plasmid of pFC.
      Largescale pFL25 plasmid was extracted, purified, and cleaved with restriction
      endonuclease EcoR I, Sal I, Pvu I, then subcloned into vector pUC19 as 1.9 kb,
      0.9 kb, 0.65 kb fragments respectively. Recomminant plasmids were selected by
      alpha-complementation and determined by restriction endonuclease analysis. DNA
      sequencing was performed by the dideoxy polymerase chain termination method.
      Partial nucleotide sequence(1-78 nucleotide position) of the gene was found to be
      highly homologous (97%) with the gene coding for TEM-52 extended spectrum beta
      lactamase of K. pneumonise, suggesting that the beta-lactamase coded by the
      cefoperazone resistant gene might be derived from TEM-type beta-lactamase.

PMID- 12212273
TI  - [High-level expression of human acidic fibroblast growth factor in E. coli and
      its purification].
AB  - A reconstructed human acidic fibroblast growth factor (haFGF) cDNA was cloned
      into the expression vector pkk223-3, and the expression in Escherichia coli.
      JM109 was induced by IPTG induction; the expression level of the recombinant
      haFGF was about 80 mg/L. The expressed haFGF was purified to identity by heparin
      affinity chromatography and the recovery rate of haFGF was 65%. The specific
      activity of the purified haFGF was ED50 4.6 ng/ml. The characters of recombinant
      haFGF was identical to that of natural one.

PMID- 12212270
TI  - [Alignment of DNA sequences of ompL1 genes of insert fragment of recombinant
      plasmid, pDC38 of L. interrogans serovar lai and L. kirschneri].
AB  - In a previous study a genomic library of L. interrogans serovar lai was
      constructed by the present authors. Hybridization analysis (In situ, dot blot,
      Southern blot) with the DNA fragment containing OmpL1 (alpha-32P labeled) was
      performed. One of positive clones designated pDC38, was analyzed with 9
      restriction enzymes (EcoRI, Bam HI, Hind III, Bgl, XbalI, ScaI, KpnI, PstI, Dra
      II). DNA hybridization was applied to analyze the homology of the recombinant
      fragment of ompL1 with the DNA of 18 strains of L. interrogans. The results
      showed that the homology of fragments of ompL1 were present in pathogenic
      Leptospira strains, but they were not in the non-pathogenic Leptospira biflexa
      strain Patoc I, Leptonema illini strain 3055. Therefore, Dr. David A. Haake
      performed the sequencing of pDC38. The results showed that pDC38 contained two
      inserts of 2.7 kb and 3.0 kb. The 3.0 insert contained a complete copy of the
      ompL1 gene. Dr. David A. Haake amplified the ompL1 gene using PCR primers
      specific for the ends of the gene and cloned the amplicon into pBluescript KS for
      sequencing. The alignment of complete DNA sequences of ompL1 of L. kirschneri and
      L. interrogans serovar lai showed the similarity of nucleotide sequences was 90%,
      variation was 10%. The derived amino acid sequence showed there was a high degree
      of amino acid sequence homology with ompL1 of L. kirschneri. These findings
      indicated that ompL1 gene was one of the important outer membrane protein genes
      in the L. interrogans serovar lai and using the probe pDC38 might provide a good
      tool for classification and identification of Leptospira.

PMID- 12212274
TI  - [Detection of HNP1 gene expression by RT-PCR in transfected tracheal epithelial
      cells].
AB  - By using lipofection reagent DOSPER, the plasmid vector carrying the human
      neutrophil defensin HNP1 gene(pBabe-Neo-HNP1) was transferred into human, rabbit
      tracheal epithelial cells cultured in serum-free complement medium. Determination
      of HNP1 mRNA expression in tracheal epithelial cells was performed by reverse
      transcription-polymerase chain reaction (RT-PCR). The result showed that HNP1
      gene expression was detected both in human and rabbit transfected epithelial
      cells; while in untransfected epithelial cells, no specific signals were detected
      by RT-PCR. This result and the result of our previous determination by
      immunocytochemical staining both demonstrated that the epithelial cells could
      express the antibiotic peptide when transfected with its gene, suggesting that
      the mucosal antibiotic peptide gene transfer might develop a new antimicrobial
      approach to prevention and treatment of respiratory infections.

PMID- 12212275
TI  - [Study on the contents of serum HDL subclasses in type N hyperlipidemics].
AB  - Contents of serum HDL subclasses in normolipidemics (n = 24) and type IV
      hyperlipidemics (n = 24) were determined using two-dimensional gel
      electrophoresis associated with immunodetection method. The results showed that
      the contents of pre-beta 1 HDL (P < 0.001) and HDL3a (P < 0.05) increased
      significantly and that of HDL2b (P < 0.001) decreased significantly in
      hyperlipidemics, compared with normolipidemics. Serum TG concentrations of
      hyperlipidemics showed positive correlation with pre-beta 1 HDL (r = 0.582) and
      HDL3a (r = 0.692) and negative correlation with HDL2b (r = -0.506) and HDL2a (r =
      -0.552). These results indicated that the maturation of HDL could be abnormal in
      type IV hyperlipidemics.

PMID- 12212276
TI  - [Free radicals on cataracts induced by sodium selenite studied by ESR and LPO].
AB  - We made a electron spin resonance (ESR) study on rat cataracts induced by
      Na2SeO3. A signal was detected at about g = 2.0026, and the content of electron
      spins (CES) in lens of rat administrated Na2SeO3 for a short time is higher than
      that of control significantly. At the late stage of cataracts, the content of CES
      was lower than normal level. The results of kinetics analysis showed that the CES
      grow up with the administration of Na2SeO3 and decays in index-law after
      administration. The results suggested that free radical scavengers or
      antioxidants should be useful for preventing cataracts at initial stage of the
      oxidation damage to lens, but they could aggravate cataracts at late stage of
      cataracts. This can explain the controversy about the curative effect of
      antioxidant to cataracts.

PMID- 12212277
TI  - [Changes of telomere length in human nasopharyngeal carcinoma].
AB  - Using Southern hybridization, we analysed the telomere length from thirty
      patients with nasopharyngeal carcinoma and demonstrated telomere reduction in
      these individuals when compared with their age-matched controls. Of the 30
      samples, 16.67% had telomere elongation, 76.67% had telomere reduction and 6.67%
      exhibited equal lengths as compared with the controls. Analysis of leukocytes
      from 30 controls indicated that the telomere length decreased (average 39 base
      Pairs Per year) with aging and a statistically significant correlation between
      the length and age was noted (r = -0.3913, P < 0.05). These results suggest that
      the consequences of telomere shortening in nasopharyngeal carcinoma may lead to
      chromosome instability.

PMID- 12212278
TI  - [Expression of P53 protein in premalignant lesion and carcinoma of larynx].
AB  - To investigate the expression of P53 protein in the premalignant lesion and
      carcinoma of laryngeal epithelium, the authors used DO-7, an antibody to wild and
      mutant type P53 protein. Eleven cases of simple hyperplasia of epithelium (SHE),
      32 cases of atypical hyperplasia of epithelium (AHE) and 42 cases of laryngeal
      squamous cell carcinoma (LSCC) were examined by ABC technique. The results showed
      that the overexpression of P53 protein were 0%, 31.25% and 52.38% in SHE, AHE and
      LSCC, respectively. The positive rate of P53 protein were 0%, 33.33% and 75.00%
      in mild, moderate and severe AHE, respectively. In well, moderately and poorly
      differentiated carcinomas of larynx, the positive rates were 62.50%, 76.92% and
      15.39%, respectively. There were highly significant differences (P < 0.01). No
      correlation was found between the P53 protein overexpression and the clinical
      stages, neck lymph node metastasis, local recurrence and, survival of LSCC. The
      results suggest that the overexpression of P53 protein may play a role in the
      pathogenesis and development of LSCC.

PMID- 12212279
TI  - [Expression of heat shock protein (HSP70) in normal endometrium and endometrial
      carcinomas].
AB  - Expression of heat shock protein 70 (HSP70) in normal endometrium tissue and
      endometrial carcinoma was analyzed by the present authors to determine the
      relationship between HSP70 expression and the prognosis of endometrial
      carcinomas. The immunohistochemical reactivity of monoclonal antibodies against
      HSP70 was examined in 44 endometrial carcinomas and 40 normal endometria HSP70
      respectively. HSP70 was expressed stronger in carcinomas than in normal.
      Expression of HSP70 was found in 56.82% of endometrial carcinomas and was well
      correlated with histological grade (P < 0.05). These results suggest that HSP70
      may play a role in the prognosis of endometrial carcinomas.

PMID- 12212280
TI  - [The effects of combined use of multiple growth factors on proliferation and
      differentiation of human osteoblast-like cells].
AB  - Four growth factors PDGF, bFGF, IGF-II and TGF-beta, which is believed to have
      biological effects on bone cells, were examined in this study. The aim was to
      assess the effects of combinations of three and four growth factors on the
      proliferation and differentiation of osteoblast-like cells. The incorporation of
      3H-TdR, 3H-Proline of osteoblast-like cells and alkaline phosphatase content of
      the cells were tested. The results showed the combinations of three and four
      growth factors stimulated the synthesis of DNA, collagen and ALP of osteoblast
      like cells. These four growth factors interacted synergistically. The
      combinations of three and four growth factors showed stronger promoting effect on
      osteoblast-like cells, compared with the combinations of two growth factors.
      These findings suggest that the combined use of growth factors be a potential way
      of bone defect reconstruction and treatment of human bone disease.

PMID- 12212281
TI  - [Effect of transforming growth factor-beta on proliferation cycle of epiphyseal
      chondrocyte].
AB  - In order to investigate the effect of transforming growth factor-beta (TGF-beta)
      on chondrocyte proliferation cycle, we used flow-cytometry to assess the
      epiphyseal chondrocyte of embryonic chick femora which was cultured in free-serum
      media and treated with TGF-beta. The results showed that after treated with TGF
      beta for 24 h, the proliferation indexes(PIs) of experimental groups(0.11 ng,
      0.33 ng, 1.00 ng/ml) were lower than the PIs of the control groups, but the PI of
      3.00 ng/ml group was higher than that of the control group (P < 0.001). After
      treated for 48 h, except the 0.11 ng/ml group, the PIs of experimental groups
      were lower than those of the control (P < 0.001). And after treated for 96 h, the
      PIs of all groups were higher than those of the control; the PI of the 0.33 ng/ml
      group was the highest (P < 0.001). These suggest that after treated in varied
      time and dosage, the effect of TGF-beta on epiphyseal chondrocyte is obvious, and
      TGF-beta on epiphyseal chondrocyte is obvious, and TGF-beta can inhibit
      chondrocyte proliferation first, and then its effect on chondrocyte can transform
      from inhibition into proliferation.

PMID- 12212282
TI  - [Genetic polymorphism at D3S1545 locus in Chengdu Han and Dali Bai populations in
      China].
AB  - The objective of this study was to understand the distribution of the genetic
      polymorphisms of STR locus D3S1545 in Chinese populations. EDTA-blood specimens
      were collected from 148 healthy unrelated Han individuals in Chengdu and 96
      healthy unrelated Bai individuals in Dali. The DNA samples were extracted using
      Chelex method, and then they were amplified by PCR technique. PAGE horizontal
      electrophoresis was used for typing the PCR product. The results there were nine
      alleles at D3S1545 locus in Chengdu Han population and six alleles at D3S1545
      locus in Dali Bai population. The allele frequencies of Chengdu Han population
      were D3S1545 * 8:0.0642; D3S1545 * 9:0.0034; D3S1545 * 10:0.0068; D3S1545 *
      11:0.0203; D3S1545 * 12:0.1824; D3S1545 * 13:0.3075; D3S1545 * 14:0.3243; D3S1545
      * 15:0.0844; D3S1545 * 16:0.0068; and 23 genotypes were observed. The allele
      frequencies of Dali Bai population were D3S1545 * 8:0.00781; D3S1545 * 11:0.0261;
      D3S1545 * 12:0.1719; D3S1545 * 13:0.3906; D3S1545 * 14:0.2448; D3S1545 *
      15:0.0885; and 16 genotypes were observed. The results of test for Hardy-Weinberg
      equilibrium showed that the genotype distributions observed at the populations
      were correspondent with the expected. These findings suggest that the allele
      frequencies at D3S1545 locus in Chengdu Hans have not remarkable different from
      those in the Bai population of Dali. D3S1545 may be a useful marker for paternity
      test and personal identification of biological stain.

PMID- 12212283
TI  - [Characteristics of chord time constant and F-V curve configuration in testing
      small airway functions for smokers].
AB  - To study the significance of chord time constant (tau ch) and F-V curve
      configuration in testing small airway function for smokers, the routine
      ventilatory functions, chord time constant (tau ch) and F-V curve configurations
      were studied in 116 passive and active (light, heavy) smokers. The tau ch was
      calculated with Knudson's method, tau ch = V/V. RESULTS: The distribution of
      convex type rose with the degree of smoking. The tau ch50 in heavy smokers and
      convex F-V curve prolongated to 130% of predicted value; tau ch50 in light
      smokers prolongated to 120%. These reflected that there were different degrees of
      disturbance in small airway functions of smokers and suggested that tau ch50
      should be a sensitive and specific index for testing small airway functions. On
      the other hand, the tau ch75, tau ch50 and tau ch25 by the present authors
      previously measured in patients with chronic obstructive pulmonary diseases
      (COPD) all prolongated with the severity of the disease, which reflected that
      both large and small airways were affected. Therefore it is concluded that in
      terms of clinical implications the specificity of tau ch50 for small airway
      functions and the prolongation of tau ch with the severity of COPD are useful
      indexes.

PMID- 12212284
TI  - [Application of in vitro micronucleus tests using L5178Y mouse lymphoma and WTK1
      human lymphoblastoid cell lines to antimutagenicity assay].
AB  - In the in vitro micronucleus (MN) tests using L5178Y mouse lymphoma and WTK1
      human lymphoblastoid cell lines, 2 well-known antimutagens, Vitamin C (Vc) and
      the sodium and copper salt of chlorophyll (Chl), were tested to evaluate their
      ability to inhibit the mutagenicity of mitomycin C(MMC). Three kinds of treatment
      were designed, namely the simultaneous treatment with Vc (or Chl) and MMC, the
      use of Vc (or Chl) before the use of MMC, and the use of Vc (or Chl) after the
      use of MMC. The results showed that Vc and Chl had no MN inductivity in the two
      cell lines; that simultaneous treatment with Vc and MMC and pre-treatment with Vc
      effectively reduced MMC-induced MN cell frequencies; and that simultaneous
      treatment and pre-treatment with Chl at dose level of 0.12 mg/ml, significantly
      reduced MMC-induced MN cell frequencies of L5178Y cells. The antimutagenic effect
      of Chl on WTK1 cells was found in simultaneous and pre-treatment at dose levels
      of 0.12 and 0.06 mg/ml.

PMID- 12212285
TI  - [Mesothelioma in rats following-intrapleural-injection of crocidolite].
AB  - In order to investigate the potential of pleural mesothelioma induced by
      crocidolite, author collected samples from four county areas (Dayao, Yaoan,
      Muding and Yanyuan) in China. A suspension of 1 ml containing 20 mg crocidolite
      fiber was injected into the right pleural cavity of each rat in various test
      groups and UICC crocidolite group, totally 40 mg. The negative control was given
      saline. The results showed that the incidence of mesothelioma was 56.0%-68.8% (in
      which the rate of induction in Yanyuan group was the highest), and the survival
      time of the first case of mesothelioma was 273-347 days in the test groups, the
      Yanyuan group had shorter latency, and the mean survival days of the rats with
      mesothelioma for four groups were 560, 490, 593 and 498 days respectively; the
      shortest mean survival time was that for Yanyuan group. The major histological
      type of mesothelioma induced by crocidolite was the fibrous type. The degree of
      differentiation in all mesotheliomas was mainly intermediate and low. The results
      suggested that when rats were intrapleurally inoculated with samples of
      crocidolite and saline, an appreciable proportion of animals developed
      mesothelioma except those of the saline group. Compared with other groups, the
      Yanyuan group had stronger potential of crocidolite-induced mesothelioma.

PMID- 12212286
TI  - [Influence of intravenous-immunoglobulin on T lymphocyte subsets, NK cell and
      some cytokines in mice with experimental viral myocarditis].
AB  - This study sought to gain an insight into the immunological pathogenesis of viral
      myocarditis and the mechanism of therapeutic action of intravenous-immunoglobulin
      (IVIG) on the disease, BALB/c mice were randomized into four groups: normal
      control group; "myocarditis model group", inoculated intraperitoneally with CVB3;
      "IVIG protection group", injected intraperitoneally with CVB3 and IVIG; and "IVIG
      treatment groups", injected intraperitoneally with CVB3 and IVIG. The amount of T
      cell in different T cell subsets and the activities of NK cell, IL-1 and IL-2
      were assayed using spleen specimen while peripheral blood was used to measure TNF
      activity. The results showed: that in comparison with normal control, all spleen
      T cell subsets decreased in amount in myocarditis model group, so did its NK cell
      activity while its IL-1, IL-2 and TNF activities increased significantly. When
      compared with myocarditis model group, however, both IVIG protection group and
      IVIG treatment group showed significant elevation of NK cell activity and T cell
      subsets but reduced IL-1, IL-2 and TNF activities with no remarkable change in T
      cell subsets. The results of suggest that the immunological injury mediated by T
      cells plays a critical role in the pathogenesis of viral myocarditis. The
      protective and therapeutic effects of IVIG on the murine CVB3 myocarditis and the
      related immunological evidence of its actions may indicate the prospect that IVIG
      will become a potent and safe treatment for viral myocarditis in human.

PMID- 12212287
TI  - [Expression of ET-1 and Pr ET-1 mRNA in kidney of early diabetic rats].
AB  - The purpose of this study was to explore the role of endothelin 1 (ET-1) and pr
      ET-1 mRNA in kidney of early diabetic rats. The location and level of ET-1 were
      determined by immuno-histochemical staining; ET-1 cDNA probe was used for in situ
      hybridization. The expressions of ET-1 and ET-1 mENA in the kidneys of 24 early
      diabetic rats were detected by microscopy and Mia-2000 patho-image-analysis
      system. The results revealed that the ET-1 mRNA and ET-1 were principally
      distributed in the glomerular endothelial cells, mesangial cells, smooth muscle
      cells of vessels, epithelial cell lining tubules and collecting ducts, showing no
      difference in the distribution over kidney, but the expressions of ET-1 and ET-1
      mRNA were higher in the renal medulla. The levels of ET-1 and ET-1 mRNA in
      glomeruli significantly decreased at week 1 and week 2(P < 0.05), but increased
      at week 4(P < 0.05). However, the levels of ET-1 and ET-1 mRNA continually
      increased from week 1 to week 4 in the medulla of diabetic rats. These data
      suggest that ET-1 and ET-1 mRNA may induce the glomerular hyperperfusion and
      damage the tubulointerstitial of the kidneys in early diabetic rats.

PMID- 12212289
TI  - [Influence of different total parenteral nutrition support upon hepatic
      regeneration after partial hepatectomy in rats].
AB  - This study was designed to investigate the effects of different TPN on liver
      regeneration after partial hepatectomy in rats. Forty Wistar rats were randomly
      divided into four groups. Groups A and B (normal rats) received BCAA-enriched TPN
      (45% BCAAs) and standard TPN (24% BCAAs) respectively after 34% hepatectomy;
      Groups C and D (rats with cirrhosis of liver) received the same TPN as Groups A
      and B received respectively after 34% hepatectomy. On the third day after
      operation, all rats were killed and specimens of liver and blood were taken for
      measurement of activity of liver regeneration. The results showed that DNA
      synthesis rate and mitosis rate in Groups A and B were significantly greater than
      those in Groups C and D respectively; RLR, DNA synthesis rate and mitosis rate in
      Groups A and C were significantly higher than those in Groups B and D
      respectively. These suggest that the effect of the same TPN on liver regeneration
      in normal rats is better than that in cirrhosis rats and that BCAA-enriched TPN
      can provide more excellent supplementation than standard TPN can do either in
      normal liver or cirrhosis liver after partial hepatectomy.

PMID- 12212288
TI  - [Change of high density lipoprotein receptor of hepatocyte during cholesterol
      gallstone formation in rabbit model].
AB  - In order to study the formation of cholesterol gallstone through rabbit model
      which was induced by high cholesterol diet (HCD), we investigated the high
      density lipoprotein receptor (HDLr) activities of hepatocytes, total bile acids
      and cholesterol of common duct bile at 1 week(1 w), 2 weeks(2 w), 3 weeks (3 w)
      and 4 weeks(4 w) in comparison with those of a control group respectively. The
      results were as follows: 1. The HDLr Bmax decreased and the kd value increased
      significantly (1 w group vs control group, P < 0.05); In 2 w group the two
      variables recovered to the level of control group; and after that, the HDLr Bmax
      increased and Kd value decreased markedly (3 w and 4 w groups vs control group, P
      < 0.05). 2. Total bile acids in bile increased slightly in 1 w group (vs control
      group, P > 0.05), then decreased in 2 w, 3 w and 4 w groups (4 w group vs control
      group, P < 0.05). 3. The concentration of cholesterol in bile increased gradually
      as the time of feeding HCD went on (3 w and 4 w groups vs control group, P <
      0.05). The results demonstrated that owing to the intake of HCD with the passage
      of time, the activity of HDLr was up at the beginning and down gradually in the
      rest period. The change in concentrations of bile acids was similar to that of
      HDLr, and the concentration of cholesterol in bile was foreign to the change of
      HDLr. These results suggest that the decrease of HDLr activity may cause the
      absence of material for bile acids synthesis and it may play an important role in
      the formation of gallstone.

PMID- 12212291
TI  - [Clinical usefulness of serum IFN-gamma level in patients with chronic
      obstructive pulmonary disease].
AB  - The objective of this study was to gain a clear idea of rule of change in serum
      IFN-gamma level in patients with chronic obstructive pulmonary disease and to
      evaluate the clinical usefulness of IFN-gamma as a marker of immune condition.
      The serum IFN-gamma levels of 15 patients with chronic bronchitis, 15 patients
      with cor pulmonale, 15 patients with acute bronchitis, and 15 normal subjects
      were measured by radio-immuno-assay. Differences between the four groups were
      tested, and in the chronic bronchitis group, the serum IFN-gamma levels, before
      and after treatment were compared. The results showed that compared with the
      normal group (0.8 +/- 0.17 IU/ml), the serum level changed little in the cor
      pulmonale group (0.93 +/- 0.25 IU/ml); it was not higher in the chronic
      bronchitis group (1.23 +/- 0.39 IU/ml, P > 0.05), but it went up significantly
      after treatment for 7 days (1.84 +/- 0.51 IU/ml, P < 0.05). The highest level of
      IFN-gamma was noted in the acute bronchitis group (2.24 +/- 0.71 IU/ml, P <
      0.01). There was a significant difference compared with other groups (P < 0.01).
      These results suggest that relative deficiency of serum IFN-gamma may be a factor
      inducing repeated respiratory infection, and the serum level of IFN-gamma can be
      used as an index to assess the immune condition of patients with chronic
      obstructive pulmonary disease.

PMID- 12212290
TI  - [Role of sera from peptic ulcer patients in cell proliferation of human gastric
      carcinoma].
AB  - This study aimed at the relationship of helicobacter pylori infection to gastric
      carcinoma pathogenesis. Forty-nine serum samples from patients with gastric and
      duodenal ulcer and 20 serum sample from normal subjects were collected for the
      assessment of serum gastrin by radioimmunoassay (RIA) and serum IgG, IgA and IgM
      antibodies against H. pylori by ELISA respectively. The patients, serum samples
      were divided into four groups for observations on whether the sera would affect
      the cell proliferation of HAC803 derived from human gastric carcinoma and of HT29
      from human colonic carcinoma cultured in vitro. The cell proliferation was
      determined by MIT assay. The results showed that the level of serogastrin in
      gastric and duodenal ulcer was significantly higher than that in normal control
      (139.6 +/- 38.17 pg/ml vs 63.12 +/- 28.7 pg/ml, P < 0.01). As for the sera of
      ulcer subjects, the highest anti-HpIgG group (group A) and the highest anti-Hp
      IgA group (group B) displayed a significantly enhanced cell proliferation of
      human gastric carcinoma (P < 0.05), especially group B. But all the four groups
      had less significant increase in cell proliferation of human colonic carcinoma (P
      > 0.05). These findings indicate that, in the highest anti-HpIgG group and the
      highest IgA group of the peptic ulcer subjects infected by H. pylori, the sera
      can enhance cell proliferation of gastric carcinoma, however the role is less
      associated with serum gastrin.

PMID- 12212292
TI  - [Effect of in vitro interferon on bone marrow megakaryocyte in patients with
      idiopathic thrombocytopenic purpura].
AB  - The effect of rIFN alpha-2a on the megakaryocyte colony growth and maturation was
      observed in 33 patients with idiopathic thrombocytopenic purpura (CITP) in vitro
      by plasma clot cultures and by GP III a McAb and ABC kit. Twenty five healthy
      persons were in the control group. The results showed that the number of colony
      formation units of megakaryocyte in the patients was similar to that in the
      controls, but the diameter and area levels of megakaryocyte in the patients were
      lower. The ratio of inhibition of rIFN alpha-2a on megakaryocyte progenitors
      colony growth was significantly lower in the patients and was lowest in the group
      with increasing number of megakaryocytes on bone marrow smear. The rIFN alpha-2a
      had no effect on promoting the megakaryocyte maturation. Since this study has
      indicated that the inhibition of rIFN alpha-2a on colony formation unit of
      megakaryocyte is slight in CITP, interferon therapy should be a suitable
      prescription for the CITP patients who have an increasing number of megakaryocyte
      on bone marrow smear.

PMID- 12212293
TI  - [The relationship between nasopharynx surface-active agents and otitis media
      effusion].
AB  - This experiment was done with a view to exploring the etiologic mechanism and new
      therapy of otitis media effusion (OME). The amount of lecithin, which is
      representative of the surfactants in the nasopharynx irrigation wash liquid, was
      determined by photometry in 40 cases OME and 40 normal controls. The results
      showed the surfactant of otitis media effusion (8.637 +/- 2.730 mg/L) was
      significantly lower than that of normal (39.212 +/- 2.437 mg/L) in the
      nasopharynx irrigation wash liquid (P < 0.01). The surfactant of child group of
      OME (8.062 +/- 2.925 mg/L) significantly lower than that of normal control(39.787
      +/- 2.557 mg/L, P < 0.01). The surfactant of otitis media effusion in the
      nasopharynx irrigation wash liquid was not associated with the course of OME.
      These data suggest that the surfactant reduction in the nasopharynx could
      indirectly reflect the level of the surfactant in the eustachian tube and the
      middle ear and influence the eustachian tube function. Surfactant reduction may
      be one of the etiologic mechanisms of OME. Increasing the surfactant in the
      nasopharynx and eustachian tube could be beneficial to reducing the persistent
      otitis media effusion.

PMID- 12212294
TI  - [Changes of placental nitric oxide synthase in patients with pregnancy induced
      hypertension].
AB  - The objective of this study was to determine whether the expression of placental
      endothelial nitric oxide synthase (eNOS) and/or inducible nitric oxide synthase
      (iNOS) are changed in pregnancy induced hypertension (PIH). The placentas of 32
      patients with PIH and 32 normal pregnancies were studied by immunohistochemistry
      (Avidin-Biotin-Complex method). The results showed there were eNOS and iNOS
      antigens in placental tissues from PIH and normal pregnancy. They were all
      localized in placental villi and syncytiotrophoblast cells. The expression of
      placenta eNOS decreased significantly in patients with PIH as compared with that
      of normal pregnancy. The expression of placenta eNOS in mild PIH was higher than
      that of moderate or severe PIH (P < 0.025, P < 0.005, respectively). There was a
      negative correlation between blood pressure and the expression of eNOS in
      placenta (P < 0.0005). There was no significant difference between the expression
      of iNOS in placenta with PIH and that in normal pregnancy. Also, there was no
      significant difference of the expression of iNOS in placenta between the mild and
      moderate PIH, or the mild and severe PIH. Furthermore, there was no correlation
      between blood pressure and the expression of iNOS in placenta with PIH. It is
      concluded that the decrease of the expression of eNOS in placenta may be
      associated with the pathogenesis of PIH.

PMID- 12212295
TI  - [Study of the carrying of respiratory tract viruses in steroid-responsive and
      simple nephrotic syndrome].
AB  - This study aimed to investigate the relationship between the carrying of
      respiratory tract viruses and the quantitative change of urinary protein of the
      steroid-responsive and simple nephrotic syndrome (SRSNS), and to assess the
      function of respiratory tract viruses in the triggering of the SRSNS, 37 children
      with nephrotic syndrome underwent the examination of respiratory tract viruses
      (APAAP method) once a week when they were hospitalized from August 1997 to March
      1998. Among them, 17 children had simple nephrotic syndrome and 10 had nephritic
      nephrosis. Moreover, 18 children with respiratory infection in the same season
      were chosen as the control and were subjected to the examination of respiratory
      tract viruses by the same method. In the cases of SRSNS, the percentage for the
      carrying of respiratory tract viruses increases obviously in the acme, the
      percentage for the carrying of respiratory tract viruses of SRSNS has close
      relationship with the quantity of urinary protein (P < 0.05). There is no
      difference between the constitution of the category of the viruses carried in the
      acme of SRSNS and that of the viruses in the control (P > 0.05). The most
      frequently detected respiratory tract viruses in the acme of SRSNS is RNA virus,
      and that in the control is the same (P > 0.05). In the acme of SRSNS, most
      children have no symptoms of respiratory infection although respiratory tract
      viruses were detected. In the SRSNS, the percentage for the carrying of
      respiratory tract viruses increases obviously in the acme, it has an important
      relationship with the quantitative change of urinary protein. The category of the
      respiratory tract viruses detected in the SRSNS has a relationship with the
      season, this may be the reason why the cases of SRSNS so easily happen and
      relapse in this season. RNA virus perhaps plays an important role in the
      triggering of this disease, including the respiratory tract viruses infection and
      the carrying of respiratory tract viruses without the symptom of respiratory
      infection.

PMID- 12212296
TI  - [Ameloblastic fibrosarcoma: an immunohistochemical and ultrastructural study of
      the mesenchymal component].
AB  - To study the characteristics of the mesenchymal cells of ameloblastic
      fibrosarcoma (AFS), three cases of AFS were studied immunohistochemically and
      ultrastructurally. The results showed that the mesenchymal component of AFS
      consisted predominantly of fibroblastic cells with a small number of
      undifferentiated cells, a few histiocytes and occasionally myofibroblastic cells
      under electron microscope. The fibroblastic cells were Vimentin positive only,
      and myofibroblastic cells were positive for Vimentin, HHF35 and alpha-SMA. The
      histiocytes were positive both for kp1 and PG-M1, suggesting that these cells
      were infiltrating cells from peripheral blood rather than histiocytic
      differentiation of tumor cells. Compared with ameloblastic fibroma, AFS showed
      much higher PCNA labeling index, suggesting higher proliferation activity of AFS.

PMID- 12212297
TI  - [Light and electron microscope observations of heart and vascular tissues in
      animals acutely infected with tubercle bacilli].
AB  - The objective of this study was to observe the heart and vascular pathological
      lesions of some animals acutely infected with H37Rv tubercle bacilli. C57 BL/6N
      mice and rabbits were used for the establishment of the models. Light sections
      were stained with HE, Z-N, MCT and BCGS-P. Ultrathin sections were stained with
      uranyl and lead citrate and examined by electron microscope. The results showed
      that tubercle bacilli were present in heart and vascular tissues. Myocardial
      fibre, pericardium and vascular tissues had various degrees of lesions. The
      lesions of myocardial fibre and pericardium were more serious than that of the
      vascular tissues. These findings suggest that the toxin of the tubercle bacilli
      can damage the tissues of the infected animals, and the excessive reproduction
      can be also a factor detrimental to the infected tissues.

PMID- 12212298
TI  - [An analysis of DNA content in 405 cases of human tumor by flow cytometry].
AB  - This study was intended to evaluate the relationship between the DNA content of
      cell cycle and the histology in human tumors. We detected the DNA content in 405
      cases of fresh human tumor tissue by means of flow cytometry and observed the
      histology of tumor with light microscopy. The occurrences of aneuploidy in 22
      cases of benign tumor and 383 cases of malignant tumor were 27% and 52%
      respectively. There were differences in aneuploidy in different histologic types
      of tumor. The aneuploidy in adenocarcinoma was about 50%, that in sarcoma was
      more than 37%, and that in squamous carcinoma less than 17%. S > or = 10, G2/m >
      or = 10 or S > or = 20, G2/m > or = 5 were present in malignant tumors, but were
      not found in benign tumors. The results suggest that there is obvious difference
      in the occurrences of aneuploidy in benign and malignant tumors and in different
      histologic type of tumor(P < 0.05). Benign and malignant tumor may be
      distinguished when SPF and G2/m reach a higher level (P < 0.01).

PMID- 12212299
TI  - [The diagnostic and therapeutic value of flexible bronchoscopy in foreign-body
      aspiration misdiagnosed as other respiratory diseases].
AB  - To explore the causes of missed diagnosis of foreign-body aspiration and
      summarize the experiences on the diagnostic and therapeutic use of flexible
      bronchoscopy (FB) in these patients. Twelve cases of foreign-body aspiration
      misdiagnosed as other respiratory diseases, confirmed by FB examination were
      analyzed. All of these patients had no histories of foreign-body aspiration, and
      no foreign-body shadows were found on their chest films. But there were
      atelectasis, hilar enlargement and obstructive pneumonia found on the films.
      Among the patients in this group, 7 cases were misdiagnosed as lung cancer, 2
      cases of pneumonia and asthma each, and 1 case as tuberculosis. The diagnoses of
      all the 12 cases were confirmed by FB examinations. The foreign-bodies of the 11
      cases were successfully grasped and taken out through the FB. This suggests that
      FB should be of great diagnostic and therapeutic value in patients with foreign
      body aspiration misdiagnosed as other respiratory diseases.

PMID- 12212300
TI  - [Study on the mechanism of glutamate mediated neurotoxicity by cortical neuron
      culture technique in vitro].
AB  - This study was intended to further explain the mechanism of glutamate (Glu)
      mediated neurotoxicity. The concentrations of TCa and Ca2+ i were measured in 32
      cortical neuron cultures, which were divided into four groups: normal control
      group (n = 8); 0.5 mmol/L Glu group (Glu group n = 8); 0.5 mmol/L Glu + 100
      mmol/L Nimodipine group (antagonist I, n = 8); 0.5 mmol/L Glu + 12 mumol/L MK-801
      group (antagonist II, n = 8). The results showed that TCa and Ca2+ i
      concentrations in Glu group were significantly higher than those in normal
      control group (P < 0.05); TCa and Ca2+i in both antagonist I and II groups were
      evidently lower than those in Glu group (P < 0.05); No difference was found
      between antagonist I and II groups. The results suggest that Glu neurotoxicity is
      due to the intracellular calcium overload, which may be from the pathway of
      voltage-dependent calcium channels (VDCCs) and NMDA receptor-operated channels
      (NROCs).

PMID- 12212301
TI  - [A clinical study of sudden death in patients with type 2 diabetes mellitus].
AB  - This study aimed to investigate the clinical characteristics of sudden death (SD)
      in type 2 diabetes mellitus (DM2). Clinical data from 1988 through 1996 in our
      hospital showed that 130 hospitalized patients with DM2 died, and 17 of them died
      of SD (13.08%). These 17 SD patients were pair-matched with 17 DM2 patients who
      were alive in the same period. The results revealed that the SD group had longer
      clinical DM duration, more chronic diabetic complications and higher blood
      pressure. In the direct causes of SD, cardiac SD accounted for 76.47%. The others
      were non-cardiac factors, including cerebral hemorrhage, hyperkalemia from
      diabetic nephropathy with renal failure and respiratory tract obstruction from
      lung infection. The triggering causes included eating, defecting, lung infection,
      strenuous attempt, hypoglycemia and surgical operation. To reduce the rate of SD
      in DM2, it is necessary and vital to treat the DM2 itself, and to take positive
      steps to prevent the onset of SD in high risk patients.

PMID- 12212302
TI  - [Effect of enoxacin on pharmacokinetics of theophylline in rats].
AB  - In order to obtain an experimental evidence for Enoxacin(ENX) to be correctly
      used in clinical treatment, we studied the effect of ENX on the pharmacokinetic
      parameters of theophylline(TP). A single oral dose of TP 20 mg/kg was given to
      rats and ENX(300 mg/kg, 450 mg/kg) was co-administered orally three times to
      those rats. The plasma concentrations of TP were determined by HPLC after TP was
      administered 1, 2, 3, 5, 7, 12 and 24 hrs. The results showed that TP was
      eliminated by one compartment model. TP plasma concentrations and AUC were
      significantly increased. T1/2 beta of TP was prolonged. The total clearance of TP
      was decreased when compared with the control. This interaction was dose
      dependent. It was concluded that the interaction between ENX and TP existed.
      Concomitant use of ENX with TP should be avoided.

PMID- 12212303
TI  - [Study on the pharmacokinetics of the liver targeted mitoxantrone polylactic acid
      extended-release nanoparticles in rabbits].
AB  - HPLC was used to analyse the drug concentrations in blood. The 3p87 (practical
      pharmacokinetic program-version) was used to calculate the parameters of DHAQ-PLA
      NP lyophilization injection and DHAQ injection through i.v. administration in
      rabbit blood. The concentration-time curves of the two kinds of preparations were
      in keeping with the three-compartment model. The drug concentrations were
      calculated according to the selecting pharmaceutical model and parameters. The
      calculated drug concentrations agreed well with the observed. The lyophilization
      injection sustained the eliminating process in vivo.

PMID- 12212304
TI  - [The influential factors in using cadmium reduction method for measurement of the
      stable products of NO--nitrates and nitrites].
AB  - To establish an efficient assay method for detecting nitric oxide indirectly, we
      compared the effects of cadmium filing, 5 mmol/L and 80 mmol/L copperized cadmium
      filing on the measurement of nitrates and nitrites (the stable products of NO)
      using the cadmium reduction method. The results demonstrated that cadmium filing
      was the most efficient cadmium preparations (P < 0.001). It's mean reduction rate
      was 96%, and it showed stronger reduction effectiveness in deproteinization cell
      culture media. The results indicated that cadmium filing has strong anti
      interference capacity in biological fluid. We recommend the cadmium filing
      reduction method because it is simple, practical, inexpensive, highly efficient
      and can be performed in ordinary laboratories.

PMID- 12212305
TI  - [Left ventricular function evaluation after mitral valve replacement with
      preservation the subvalvular apparatus].
AB  - The objective of this study was to evaluate the left ventricular function after
      mitral valve replacement (MVR) with preservation of all chordae. Fourteen
      patients with a diagnosis of mitral regurgitation were studied. These patients, 4
      males and 10 females, age from 24 to 59 years, who underwent mitral valve
      replacement, in which all chordae tendineae were preserved. The mean follow-up
      interval was 6 months. Preoperation and postoperation multigated equilibrium
      radionuclide angiography was performed by Elscint Helix Apex SPECT. Each patient
      was injected with 740MBq 99mTc-HSA, rest ejection fraction (global EF) of LV (%),
      regional ejection fraction (EF) of LV (%), PER/S and PFR/S were measured.
      Regional EF was calculated by the method of dividing the left ventricle into five
      segments by radial axis. The results showed that the postoperative EF of the
      whole left ventricle of the chordae-preserved patients was significantly greater
      than their preoperative EF (40.0% +/- 17.8%, to 51.6% +/- 18.2%, P < 0.02), and
      also the regional EF at the lateral wall of the chordae-preserved MVR was
      significantly greater than the preoperative regional EF (an increase from 51.0%
      +/- 18.1% to 69.7% +/- 21.2%, P < 0.01). MVR with preservation of all chordae,
      the patient's left ventricular function remarkably improved.

PMID- 12212306
TI  - [Determination of acid-base amphoteric dissociation constant of 2-methyl-5 (4)
      nitroimidazole by UV-spectrophotometry].
AB  - The 2-methyl-5(4)-nitromidazole(BH) is an ampholyte with acid and base. It is an
      intermediate of metronidazole. The amphoteric dissociation constant of BH
      determined by equimolar UV-spectrophotometry. The acidic dissociation constant
      pKa is 9.64 +/- 0.04 and the basic dissociation constant pKb is 12.98 +/- 0.02.

PMID- 12212307
TI  - [A review of methods for controlling medical costs from the point of view of cost
      effectiveness].
AB  - Cost-effectiveness analysis is a method used to evaluate the outcomes and costs
      of treatments or interventions designed to improve health. It has been widely
      regarded as an important aid to providing health care services efficiently. This
      paper reviews several measures for controlling medical costs in Japan, where a
      fee-for-service system is employed to remunerate for medical services provision.
      From the point of view of cost-effectiveness, the first step in health care
      reform for controlling medical costs should be minimizing useless medical
      services because the cost-effectiveness ratio of these tends to infinity. For the
      purpose of minimizing unserviceable provision in the field of medicine, two
      approaches must be considered. One is establishing a system so that physicians
      can act as perfect agencies for their patients. The other is encouraging academic
      research on the effectiveness of medical services.

PMID- 12212308
TI  - [A 7-year follow-up study of cases with dementia to identify predictors of
      mortality].
AB  - OBJECTIVES: To identify factors associated with mortality in cases with
      Alzheimer's disease (AD) and vascular dementia (VD), we conducted a seven-year
      follow-up study. METHODS: Subjects were recruited through three agents in
      Yamanashi prefecture. A total of 145 patients (56 men, 89 women, age at baseline
      77 +/- 7.9, 80 +/- 8.5 years respectively) with AD and VD participated in the
      follow-up study. We analyzed the relationship between demographic or clinical
      variables and their survival using a Cox regression model. RESULTS: The analysis
      revealed that increased age, male gender, the degree of global function and past
      history of a fall/fracture were associated with a decreased survival rate. The
      rate was worse for patients with VD than for those with AD. After adjusting for
      age and gender, the mortality risk ratio was 1.7 (95% confidence interval 1.1
      2.6) for the presence of a fall/fracture. The same analysis confined to 64
      subjects for whom ApoE genotyping data were available replicated the results; a
      fall/fracture was a predictor of a worse survival rate. In addition, those with
      ApoE4 tended to have better survival rate than those without (P < 0.1).
      CONCLUSION: Those who are engaged in care for AD patients should appreciate the
      importance of a fall/fracture as a predictor of survival.

PMID- 12212310
TI  - [Validity of an accelerometer for estimating daily physical activity--comparison
      with a diary method].
AB  - PURPOSE: To examine the validity of accelerometer measurement of daily physical
      activities in working adults. METHOD: Thirty one male and 29 female working in
      the civil service office of N-city were required to wear an accelerometer and to
      complete a 5-minute-interval activity diary for 2 days (one weekday and one
      weekend day). One-day energy expenditure obtained from the accelerometer was
      compared with that from the activity diary calculated from intensity (metabolic
      equivalents) of each activity and its duration. Difference and correlation
      between energy expenditure obtained with the two methods were evaluated. RESULTS:
      Although energy expenditure estimated from the activity diary was larger than
      that from accelerometer by 403.9 kcal, the results were highly correlated
      (Pearson's r = 0.846). The correlation coefficient was larger among light walkers
      than intensive walkers. When energy expenditure during bathing was excluded
      because of the non-wearability of the accelerometer, the difference between the
      methods was reduced without affecting the correlation coefficient. CONCLUSION:
      The accelerometer was concluded to be useful for measurement of daily physical
      activities for epidemiological research and health promotion in adults.

PMID- 12212311
TI  - [Relationship of normal levels of activity of daily living and daily habits among
      elderly women at home].
AB  - PURPOSE: The relationship of activities of daily living (ADL) with daily habits
      and age was investigated with a focus on the results of measurements of the
      normal speed (ordinary level: OL) and maximum speed (maximum capacity: MC) in
      performing items on a functional fitness test. The significance of the
      measurement of the ordinary level was also discussed. METHODS: The subjects were
      69 women, aged 60-90 years old, who participated in a health workshop for the
      elderly sponsored by a local municipality and who performed at least 4 items on a
      functional fitness test. Public health nurses asked subjects about habitual life
      style, subjective health status and degree of satisfaction in daily life. The ADL
      level was measured using the tests of functional fitness developed by Oida et al
      and partially revised by ourselves and physical fitness tests (grip strength, sit
      and reach, and balancing on one leg with opened eyes). OL was measured as the
      time needed to perform functional fitness items at normal speed, and MC as the
      time needed when performing these tasks as quickly as possible. RESULTS: All
      functional fitness items were accomplished significantly faster with MC than OL.
      Correlation coefficient values between OL and MC were high significant. Age was
      found to be significantly related to the hand working test (Hand-T) to evaluate
      dexterity and the rope working test (Rope-T) to evaluate self-care, except with
      the MC. An analysis of covariance with age as the covariant revealed that, with
      OL, there were relationships between Hand-T and Rope-T and the item "active at
      home," and between the zigzag walking (Zigzag-T) and Rope-T and "walking or
      riding a bicycle to go shopping." With MC, there were relationships between Hand
      T and "active at home," and between Zigzag-T and "walking of riding a bicycle to
      go shopping." Regarding physical capacity, relationships were seen between both
      hands and "high level of physical fitness" and "walking fast" and grip strength
      (Left hand), respectively. CONCLUSION: The ADL items measured in the preset study
      were related to the daily activities of elderly people. As the OL and MC results
      demonstrated a high correlation and the ADL items related with OL were found to
      have almost the same link with MC, we conclude that OL is suitable for testing
      with the advantage of safety. However, we could not explain differences in
      relationships between measurements and daily activities, pointing to a need for
      further research. Elderly people must maintain their capacity for ADL to support
      a good quality of life, and we have demonstrated the utility of measurements that
      include normal levels of activity as indicators.

PMID- 12212309
TI  - [Effects of quantity of Japanese cedar pollen, air pollution and urbanization on
      allergic rhinitis morbidity in Ibaraki prefecture].
AB  - OBJECTIVES: It has been reported that morbidity from allergic rhinitis in the
      National Health Insurance records in Ibaraki Prefecture for May correlated with
      the quantity of Japan cedar pollen scattered in each year. The purpose of the
      present investigation was to clarify the Japanese cedar pollinosis contribution
      to morbidity, and also clarifying the influence of air pollution and medical
      resources on the crisis and symptoms of allergic rhinitis. METHODS: The charts in
      four otolaryngology facilities were used for analyzing the Japan cedar pollinosis
      content with reference to the allergic rhinitis during the pollen season. The age
      adjusted morbidity of allergic rhinitis was annually compared employing data of
      National Health Insurance records for medical examinations made in May during the
      period between 1988 and 1996 in Ibaraki Prefecture. The quantity of Japanese
      cedar pollen was measured at seven area points in Ibaraki Prefecture during the
      three-year period from 1994 to 1996, and was compared with the degree of Japan
      cedar wood occupation in each municipality. Traffic volume according to
      municipalities in Ibaraki Prefecture was taken as a surrogate indicator of air
      pollution. The area otolaryngology facilities and doctors were taken as medical
      resources. Values were thus compared with allergic rhinitis morbidity. RESULTS:
      Sixty to eighty percent of the allergic rhinitis patients examined in May were
      found to be suffering from pollinosis. The quantities of Japanese cedar pollen
      scatter at the seven points in Ibaraki Prefecture varied in concert every year,
      the quantities correlating well with the area of Japanese cedar woods stands in
      each municipality in some but not in other years. The morbidity in the records of
      allergic rhinitis according to municipalities correlated negatively with the
      proportion of the population occupied in farming (r = -0.38) and with the area of
      Japanese cedar woods in each municipality (r = -0.40). The traffic volume
      calculated according to municipalities in Ibaraki Prefecture correlated
      significantly with the yearly average concentration of nitrogen dioxide (r =
      0.63, P < 0.01) and with the morbidity of allergic rhinitis. In places among the
      northern mountains of the Prefecture, both the morbidity in the records and the
      distribution of otolaryngology facilities were low. CONCLUSIONS: More than 60% of
      the morbidity from allergic rhinitis in May appeared in the National Health
      Insurance records to be associated with Japanese cedar pollinosis. This was
      confirmed by the correlation between yearly variation in morbidity and that of
      the quantity of Japanese cedar pollen scatter. As local factors increasing the
      morbidity of allergic rhinitis in the records, air pollution, urbanization and a
      greater availability of medical resources were indicated.

PMID- 12212312
TI  - [Impact of the positive appraisal of care on quality of life, purpose in life,
      and will to continue care among Japanese family caregivers of older adults:
      analysis by kinship type].
AB  - PURPOSE: The impact of positive appraisal of care (PAC) on the caregiver's
      quality of life (QL), sense of purpose in life (sense of ikigai) and will to
      continue care was examined. METHODS: Data were collected from 322 Japanese family
      caregivers of older adults who were using visiting nursing services through 21
      facilities in the Tokyo metropolitan area, and the prefectures of Shizuoka, Mie
      and Okinawa. RESULTS: The data were grouped by kinship type (husband or son,
      wife, daughter or daughter-in-law) and analyzed separately. From the multiple
      regression and logistic regression analyses, the following results were derived:
      1) The PAC was not related to the physical QL regardless of the relationship
      type; 2) The relationship depended upon the relationship type: only the PAC was
      related to the mental QL among husband and son caregivers, both the PAC and the
      negative appraisal of care (NAC) were important among wives, only the NAC among
      daughters, and none of them among daughters-in-law; 3) Both the PAC and NAC were
      related to the sense of ikigai in all caregiver types except among husband and
      son caregivers, which showed no relationship between the NAC and sense of ikigai;
      4) Both the PAC and NAC were related to will to continue care among son and
      husband caregivers, whereas only the PAC was among wives and daughters-in-law.
      Only the NAC was related among daughters. However, the difference across kinship
      type seems minimal for will to continue care. CONCLUSIONS: Understanding the PAC
      among family caregivers may be important in order to better assist them to
      improve their mental QL or sense of ikigai as well as to predict their
      continuation of caregiving at home. The impact of PAC varies depending on the
      kinship type, and it should be assessed separately with reference to this
      pariable to develop plans for appropriate assistance.

PMID- 12212313
TI  - [Evaluation of intractable diseases].
AB  - OBJECTIVE: The aim of this study was to determine priorities for specific
      intractable disease from the viewpoint of countermeasures. METHODS: A
      significance evaluation to provide a priority framework for intractable disease
      was performed with a questionnaire distributed to the staff of preventive
      medicine and public health departments of medical schools in Japan. To determine
      the actual conditions of these intractable diseases question were directed at the
      chairmen of individual clinical study groups. The priority to be assigned
      countermeasures for such diseases was obtained from the two questionnaires.
      RESULTS: When the 4 factors "rare nature of diseases," "level of clarity of
      causes and pathology," "unestablished curative treatment", and "influence on
      daily life" were evaluated using 100 point as a full score, the mean scores were
      14.5, 27.1, 28.5 and 29.9 points, respectively. In attaching importance to the
      various items, regarding the "rare nature of disease" the elements of "few
      patients nationwide" and "few specialist doctors nationwide" proved important;
      for the "level of clarity of causes and pathology," this was the case for the
      elements of "unclear triggering mechanism" and "diagnostic criteria not
      established." With the "unestablished curative treatment," the "no efficacious
      treatment available" and "low 5-year survival rate elements were important; and
      with the factor of "influence on daily life," the two most significant were "high
      proportion of patients needing assistance in daily life" and "high percentage of
      patients impeded from attending school or obtaining a job (playing a role in
      society)". CONCLUSION: When the priority among the 118 intractable diseases was
      evaluated by combining the overall results of the questionnaire survey with
      preventive medicine and public health staffs, and actual condition data from
      survey investigation of the intractable diseases among chairmen of clinical study
      groups, it was suggested that some intractable diseases whose medical expenses
      are covered by the medical aid program have a low ranking.

PMID- 12212315
TI  - [Efficacy of smoking prevention education by dentists].
AB  - PURPOSE: At the same time as generating a clear picture of high school students'
      smoking habits, we examined how effective it was for dentists to provide them
      with smoking prevention education. METHOD: We chose one high school in Hiroshima
      City and asked 1003 of its students to fill in questionnaires anonymously before
      and after a lecture given by dental faculty on smoking. On a different day the
      students' oral health was examined by dentists. FINDINGS: The higher the year of
      the students the higher the percentage of those who had smoked at some time or
      smoking now. Among students not participating in any club activities, the higher
      the year the greater the number of smokers. Among the effects of smoking the one
      known to the largest number of students was found to be lung cancer, followed by
      oral disease. The questionnaires showed the percentage of students thinking that
      their family should give up smoking had increased by 6.3% from 55.9% to 62.2% by
      the end of the lecture, indicating that it was effective. Among the contents of
      the lecture which had impressed, photographs of cancer, dental damage and
      features Buerger's disease were mentioned in particular. CONCLUSION: It is
      advisable to show some photographs of cancer and Buerger's disease as well as
      talk about how smoking damages teeth when we embark on smoking prevention
      education. Our study confirmed the need for dentists to provide this kind of
      education.

PMID- 12212314
TI  - [Relationship between activities of daily living and residential environment for
      patients receiving home oxygen therapy].
AB  - PURPOSE: The purpose of this study was to investigate the relationship between
      ADL and residential environment for patients receiving home oxygen therapy.
      METHODS: We interviewed 27 HOT patients with chronic respiratory failure, aged 53
      85, at an internal medicine outpatient clinic of a national hospital in Yokohama
      city, using a questionnaire focusing on physical condition, dyspnea, ADL, and
      residential environment. RESULTS: 1. Of the patients 21 (78%) were III-IV level
      by Hugh-Jones classification. HOT patients experienced severe dyspnea when
      climbing stairs and bathing. Their ADL was limited to within their own homes. HOT
      patients opt to use taxies more often than facilities such as buses and trains.
      2. Out of 20 patients living in a two-story house, the ADL of 16 (80%) were
      limited to downstairs. Two patients living in apartment houses without an
      elevator complained of great difficulties in going down stairs to go out. Twelve
      of the patients (44%) interviewed resided in hillside area, the distance to the
      nearest bus stop being greater than in flat area. 3. A public financial support
      for house innovation has been offered for some time, but most of the patients did
      not have any information about this system. They had not realized how their
      residential environment might affect their ADL. CONCLUSION: These results suggest
      that more education for HOT patients is needed. They should be clearly shown the
      importance of the residential environment in enhancers their ADL.

PMID- 12212316
TI  - [Levels of airborne dust by particle size in a suburb of Takamatsu, Japan].
AB  - PURPOSE: In recent years, attention has been paid to the influence of the
      particle fraction < or = 2.5 microns in diameter (PM2.5) among suspended
      particulate matter (SPM) on health. However, the present status of particle
      contamination in Japan has hitherto not been adequately clarified. To determine
      particle contamination in the outdoor air around Kagawa Medical School located on
      a hill in the suburb of Takamatsu City, we measured SPM according to diameter
      between February 1999 and January 2000. METHODS: Mass concentrations of SPM were
      determined using an Andersen air sampler and light scattering counts were
      measured using a particle counter at the same site. RESULTS: Of the entire year,
      the total SPM concentration (PM11) was 20-30 mg/m3, and the particle fraction <
      or = 2.1 microns in diameter (PM2.1) accounted for 25-60%. Both the PM11 and
      PM2.1 concentrations were the lowest in August when the wind blew mainly from
      rural areas, but high in January and February when the wind blew mainly from
      urban areas and April when yellow sand was wind borne from China. The SPM
      particle count in April was markedly high when a misty aerosol containing yellow
      sand was extent. The SPM count for each diameter class rapidly decreased after
      rainfall during passage of storm fronts, but this was especially marked for
      smaller diameters. During the measurement period in August, air from rural areas
      often passed the measurement point, and the particle concentration < or = 1
      micron in diameter was markedly lower than that in April. CONCLUSION: The results
      suggest that the SPM levels around Kagawa Medical School located in the suburb of
      Takamatsu City are associated with seasonal climate and the wind direction from
      which the prevailing blew.

PMID- 12212317
TI  - [Antiretroviral treatment of HIV-infected patients in Japan].

PMID- 12212318
TI  - [Basic studies on Vibrio vulnificus infection: isolation of V. vulnificus from
      sea water, sea mud, and oysters].
AB  - To clarify the environmental distribution of Vibrio vulnificus, sea water, sea
      mud, and oysters were examined at 13 sites, i.e. 4 sites in the Tokyo Bay
      (eastern Japan) and 9 sites (5 sites for oysters) in Tokushima Prefecture
      (western Japan). 1. V. vulnificus was isolated from 80 (54.8%) of the 146 samples
      of sea water examined. It was isolated from 19 (41.3%) of the 46 samples from
      western Japan and 61 (61.0%) of the 100 samples from eastern Japan. 2. It was
      isolated from 40 (40.8%) of the 98 samples of sea mud obtained in eastern Japan.
      3. It was isolated from 655 (30.3%) of the 2,165 samples of oysters. They were 30
      (9.7%) of 309 samples from western Japan and 625 (33.7%) of 1,856 samples from
      eastern Japan. 4. The density of V. vulnificus was 0.3-1.1 x 10(6) MPN/L in
      seawater, 0.3-1.1 x 10(5) MPN/100 g in sea mud, and 0.3-1.1 x 10(7) MPN/100 g in
      oysters. 5. Seasonally, V. vulnificus was isolated from 44 (6.2%) of the 713
      samples in spring, 450 (72.6%) of the 620 samples in summer, 264 (51.8%) of the
      510 samples in fall, and 17 (3.0%) of the 56 samples in winter. Thus, the
      isolation rates of V. vulnificus from sea water and oysters tended to be higher
      in eastern Japan than in western Japan and to be highest in summer, then, in
      fall.

PMID- 12212319
TI  - [Clinical utility of serum Candida mannan antigen detection kits using ELISA].
AB  - The clinical utility of two serum Candida mannan antigen detection kits with
      ELISA, UNIMEDI Candida and PLATERIA Candida Ag, was investigated. Thirty-four
      serum samples from 12 cases with candidemia diagnosed at Kawasaki Medical School
      Hospital in 1999 and 15 samples from 15 healthy volunteer were examined. The
      sensitivities and specificities of the two kits were 82.1% and 40.0%, 100% and
      100% respectively. This sensitivity was higher than that achieved with the
      conventional methods. However, it was realized that the discrepancy between the
      sensitivity of these two kits was quite significant. This may have been caused by
      a difference in the reactivities of the respective kits against different species
      of Candida. A combined application of these methods and other supportive
      diagnostic methods, such as serum (1-->3)-beta-D-glucan detection, will improve
      their utility. A larger number of cases should be evaluated to clarify the
      characteristics of these new kits.

PMID- 12212320
TI  - [The results of antibiotic susceptibility of gram-negative rods at Tottori
      University Hospital--the possibility of the sensible use of narrow-spectrum
      antimicrobial agents].
AB  - The control of hospital-acquired infections is a matter of social concern,
      especially in the proper use of antimicrobial agents. The fundamentals of
      treatment for infectious diseases involve the exact identification of the
      responsible bacteria, and the minimum essential use of narrow-spectrum
      antimicrobial agents for the identified bacteria. We tested the antimicrobial
      susceptibility of 13 species which belong to the gram-negative rod type and
      isolated 50 or more strains at Tottori University Hospital in 2001. We evaluated
      the susceptibility pattern for every species, and have proposed a plan for the
      sensible use of narrow-spectrum antimicrobial agents. The resistant frequency in
      the present study was equal to or lower than previously reported. We think that
      it is possible to use narrow-spectrum antimicrobial agents more often, because
      the susceptible frequency to these agents was fairly high for some species. It is
      not too much to say that the history of the development of antimicrobial agents
      has been a road to broad-spectrum. Though the proper use of antimicrobial agents
      seems to go against this view, we should remain farsighted. Not only is the
      publicity of proper use indispensable but excellent surveillance is also highly
      necessary. We hope for the establishment of a good surveillance system gifted
      with simplicity, universality, high reproduction and continuity.

PMID- 12212321
TI  - [Assessing the efficacy of antimicrobial agents based on the Japanese Respiratory
      Society Guidelines for a community-acquired pneumonia].
AB  - We evaluated the efficacy of antimicrobial agents used for patients with
      community-acquired pneumonia (CAP) based on the guidelines of Japanese
      Respiratory Society. A total of ninety-nine hospitalized patients who were
      suspected to have bacterial pneumonia at the time of admission between January,
      1998 and December, 2000 were assessed. Our conclusions were as follows. 1) The
      rate which was considered as effective by the guidelines were 83.3% (5 of 6
      cases), 98.7% (74 of 75 cases), 85.7% (12 of 14 cases), and 100% (4 of 4 cases)
      for penicillin, cephem, carbapenem and tetracycline, respectively. 2) These
      guidelines were useful and practical for identifying the etiological organisms,
      determining the severity of pneumonia and evaluating the efficacy of
      chemotherapeutic agents in CAP. 3) Gram-positive organisms were isolated more
      frequently among the "mild" group. The number of isolated gram-negative was
      increased significantly as the severity of pneumonia progressed from "mild" to
      "severe" group. 4) Factors such as body temperature and white cells count were
      not always applicable for evaluating the clinical effect in elderly cases. 5)
      Risk factors such as underlying diseases, or complications, age (over eighty
      years old) and specific etiological organisms might influence the ineffectiveness
      of antimicrobial agents among the cases that had no clinical response. 6) The
      choice of antibiotic agents for the treatment of CAP should be made with
      consideration to the local-specific profiles of each medical facility as
      described in the guidelines.

PMID- 12212322
TI  - [A case of papulonecrotic tuberculide preceded by pulmonary tuberculosis].
AB  - We experienced a rare case of papulonecrotic tuberculide (PT). A twenty-four year
      old female was referred to our hospital because she had had an eruption for the
      last for four years. Her chest X-ray revealed no abnormal shadow three years ago
      when her eruption had already appeared. This time, the skin biopsy and repeated
      chest X-ray were investigated. These results showed pulmonary tuberculosis
      accompanied with PT. Both rifampin and isoniazid were administered and apparent
      improvement was achieved after six months-of treatment. Pt also showed
      improvement. Her skin involvement was preceded by pulmonary tuberculosis.
      Nowadays, PT is a rare disease but physicians should be on the alert for this
      disease as a sign of tuberculosis.

PMID- 12212323
TI  - [A case of invasive Clostridium perfringens infection complicated intravascular
      hemolysis].
AB  - We experience a case of a 83-year-old male who was admitted complaining of
      chills, cramp, high fever and respiratory distress. His blood revealed marked
      hemolysis. Gram positive Rods was observed in the hemoliesed blood taken on
      admission. About 2 hours after admission, he suddenly fell into a critical
      condition. He died about 6 hours after admission in spite of resuscitation.
      Clostridium perfringens was detected from the blood and liver obtained by
      autopsy. We suspected that he died of acute intravascular hemolysis caused by
      alpha-toxin produced by C. perfringens. In conclusion, for a patient who has a
      high fever with strong hemolysis such as our case, C. perfringens infection
      should be considered.

PMID- 12212324
TI  - [A case of Nocardia farcinica pneumonia treated with sulfamethoxazole
      trimethoprim monitoring its serum concentration].
AB  - A 75-year-old male suffered from interstitial pneumonia in December 2000 and
      treated with predonisolone. The treatment was effective, and the dosage of
      predonisolone had been gradually tapered. In January 2001, when the dosage was 30
      mg/day, he complained of cough and yellowish sputum. The chest X-ray and CT
      revealed bilateral infiltrations with cavities. He was treated with cefozopram
      and fluconazole. However, there were no improvements. The sputa of the 2nd, 3rd,
      6th and 8th hospital days showed the presence of gram-positive branched rods,
      which were identified as Nocardia farcinica. Therefore, the treatment was changed
      to sulfamethoxazole-trimethoprim. During the treatment, serum concentration of
      sulfamethoxazole was repeatedly measured, and kept over 60 microgram/ml. He was
      swiftly recovered after the start of sulfamethoxazole-trimethoprim. This case was
      supposed to be the seventh one of N. farcinica pneumonia in Japan, and the
      measurement of the concentration of sulfamethoxazole was useful to determine its
      dosage.

PMID- 12212325
TI  - [Two cases of mixed infection of malaria diagnosed by PCR method].
AB  - We here reported two Japanese cases of mixed infections of plasmodium species,
      whose DNAs were detected using the PCR test. One case was a 31 year-old male, who
      presented fever and fatigue, and had a travel history to Kenya, Cameroon and
      Indonesia. Smear test of his peripheral blood found the presence of Plasmodium
      vivax, while nested-PCR diagnosis detected the DNAs both P. vivax and Plasmodium
      malariae. The other was a 54 year-old female suffering from general fatigue. She
      had been treated with chloroquine for falciparum malaria in Indonesia two weeks
      before. Malaria antigen test showed positive although no Plasmodium organisms
      were found in the smear test. The nested PCR detected the DNA of Plasmodium ovale
      in addition to that of Plasmodium falciparum. In conclusion, the PCR test is
      helpful and useful for detection of mixed infections of Plasmodium species.

PMID- 12212326
TI  - [A case of Pseudomans aeruginosa pneumonia complicated with multiple pustular
      skin lesions].
AB  - Pseudomonas aeruginosa is a common causative agent of septicemia in compromised
      host and the entry site of organism is most commonly the respiratory and
      genitourinary tract. P. aeruginosa septicemia is often associated with vesicular
      or pustular skin lesions, subcutaneous nodules, deep abscess, cellulites and
      bullae. We report a case of P. aeruginosa pneumonia with multiple pustular skin
      lesions on the chest and leg. A 77-year-old male was admitted to our hospital
      complaining of fever, productive cough and eruptions. Laboratory findings
      revealed a leucocytosis (14,830/microliter) and an elevated CRP (21.72 mg/dl).
      The chest radiograph and computed tomography revealed a fluid level in
      preexisting bullae and a consolidation shadow with multiple cavities in the right
      upper lobe and nodular shadow with cavity in the left lower lobe. P. aeruginosa
      strain was isolated from the bronchial lavage and pustule. Blood cultures were
      negative. Skin biopsy specimens showed histologically a dense infiltrate of
      neutrophils in the horny cell layer. He was diagnosed as Pseudomonas aeruginosa
      pneumonia complicated with multiple pustular skin lesions. He was treated with
      antimicrobial agents for 24 days and his clinical condition improved.

PMID- 12212327
TI  - Back to nature.

PMID- 12212328
TI  - Could it be ME?

PMID- 12212329
TI  - Pressure point. Interview by Charlotte Alderman.

PMID- 12212330
TI  - Winning record. Interview by Alison Moore.

PMID- 12212331
TI  - Keep in touch.

PMID- 12212333
TI  - Filling in the gaps.

PMID- 12212334
TI  - Causes of insulin resistance in childhood.
AB  - The increasing incidence of type 2 diabetes worldwide is causing concern. Genetic
      and environmental influences have been put forward to explain the origins of this
      disease, but perhaps the most convincing contributory factor is high body weight.
      The authors review the literature on the subject to identify some of the
      predisposing factors influencing healthcare practitioners' concerns about the
      issue.

PMID- 12212335
TI  - Benchmarking: implementing the process in practice.
AB  - Government guidance and policy promotes the use of benchmarks as measures against
      which practice and care can be measured. This provides the motivation for
      practitioners to make changes to improve patient care. Adopting a systematic
      approach, practitioners can implement changes in practice quickly. The process
      requires motivation and communication between professionals of all disciplines.
      It provides a forum for sharing good practice and developing a support network.
      In this article the authors outline the initial steps taken by three PCGs in
      implementing the benchmarking process as they move towards primary care trust
      status.

PMID- 12212336
TI  - Demonstrating critical analysis in academic assignments.
AB  - Nurses use critical analysis skills in their day-to-day practice, but many find
      it difficult to transfer these skills to academic course work. The author offers
      advice on how these skills can be developed and applied to academic assignments.

PMID- 12212337
TI  - The role of advanced practice nurses in a shared care diabetes practice model.

PMID- 12212338
TI  - From jelly beans to kidney beans: what diabetes educators should know about the
      glycemic index.

PMID- 12212339
TI  - Health benefits of dietary fiber for people with diabetes.

PMID- 12212340
TI  - Accuracy of self-monitoring of blood glucose: impact on diabetes management
      decisions during pregnancy.
AB  - PURPOSE: This study tested the hypothesis that the accuracy of self-monitoring of
      blood glucose (SMBG) values of patients with diabetes during pregnancy deviates
      substantially from reference values. METHODS: The patients' glucose values were
      measured on 6 different SMBG meters; reference values were from the HemoCue B
      Glucose Analyzer. Over a 5-year period, 1973 comparisons between SMBG values and
      reference values were recorded during clinic visits and used for this study. Data
      were analyzed for percent of values that varied more than +/- 10.5% and +/- 15.5%
      from the reference value. Out-of-range data at each variance level were analyzed
      to determine the impact on medical management if decisions were based solely on
      SMBG values. RESULTS: One third of SMBG readings deviated significantly, which
      could adversely affect treatment for half of these patients if diabetes
      management was based on SMBG values. At the 10.5% deviation level, 34% of SMBG
      meter readings were out of range; 54% of these would have implied erroneous
      treatment. At the 15.5% deviation level, 18% were out of range; 63% of these
      would have implied erroneous management. CONCLUSIONS: The accuracy of home meters
      should be verified at regular intervals, and SMBG values should not be the sole
      criterion for diabetes management during pregnancy.

PMID- 12212341
TI  - Tablet-breaking ability of older persons with type 2 diabetes mellitus.
AB  - PURPOSE: The purpose of this study was to assess the ability of older persons
      with type 2 diabetes to accurately break in half 2 different formulations of
      micronized glyburide tablets. METHODS: Thirty persons with type 2 diabetes, over
      age 70, were recruited from the St Louis University geriatric clinics.
      Participants were randomly assigned to 2 groups. Group A broke 30 Glynase
      Prestabs and 30 generic tablets using 2 different manual tablet-breaking methods.
      Group B broke 15 Glynase Prestabs and 15 generic tablets without instructions.
      Visual analog scales were used to assess pain and difficulty of tablet breaking.
      RESULTS: A higher percentage of successful tablet breaking was reported with
      Glynase Prestabs (80%) compared with the generic tablets (33%). Mean pain scores
      for breaking Glynase Prestabs were 0.1 (Group A) and 0.9 (Group B). Higher pain
      scores were obtained for the generic tablets (2.1 for Group A, 3.2 for Group B).
      Glynase Prestabs were easier to break in both groups, and the resultant half
      tablets showed less variance from the expected theoretical weight (50% of whole
      parent tablet weight). CONCLUSIONS: Older adults broke Glynase Prestabs more
      accurately and with less difficulty than generic micronized glyburide tablets.
      This variation in ease of tablet breaking and accuracy between different tablet
      formulations affect bioavailability and patient compliance.

PMID- 12212342
TI  - A quality improvement project for better glycemic control in hospitalized
      patients with diabetes.
AB  - PURPOSE: A quality improvement (QI) study was designed to improve nursing
      interventions that impact glycemic control in hospitalized patients with
      diabetes. The objective was to improve the timing of premeal insulin to allow a
      half hour lag time for regular insulin. METHODS: An interdisciplinary planning
      team was established that included both medical and surgical units. Data were
      collected by concurrent review of electronic charts, evaluated monthly by
      management and the diabetes clinical coordinator, and shared with staff. RESULTS:
      This QI study increased staff nurses' awareness of the importance of their role
      in achieving better glycemic control for inpatients with diabetes. By the end of
      the study, the nurses delivered premeal insulin correctly 82% of the time on the
      medical unit, 65% of the time on the cardiac unit, and 61% of the time on the
      surgical unit. Even with concerted effort, however, it was difficult to
      consistently administer regular insulin with a half hour lag time in the hospital
      environment. CONCLUSIONS: By working together with the patient, family, and other
      staff, nurses can more consistently deliver premeal insulin at appropriate times
      to help improve glycemic control in the hospitalized patient with diabetes.

PMID- 12212343
TI  - The conceptual framework of the National Diabetes Education Outcomes System
      (NDEOS).
AB  - PURPOSE: This article describes the systems-based conceptual framework for the
      definition of diabetes education outcomes and the development of the National
      Diabetes Education Outcomes System (NDEOS). METHODS: Development of the NDEOS was
      based on integrating diabetes education into the diabetes care system;
      identifying and tracking standardized learning, behavioral, and clinical outcomes
      measurements; and gathering data at the individual, program, and national levels.
      Each component was formulated based on available literature and through consensus
      with the American Association of Diabetes Educators (AADE) Outcomes Task Force
      and other multidisciplinary healthcare professionals. RESULTS: Behavior change is
      the key outcome measurement for diabetes self-management education (DSME). In
      addition, diabetes educators should collect other immediate, intermediate, and
      long-term outcomes for monitoring the impact of DSME. The NDEOS system includes
      standardized data collection tools for the participant, the educator, and the
      program manager, and provides reports at the individual, program, and national
      levels. CONCLUSIONS: By capturing outcomes data using valid, reliable, and
      evidence-based tools, the NDEOS strives to support diabetes educators and provide
      a uniform data set that can be used to influence public policy, support
      reimbursement negotiations, and assist researchers.

PMID- 12212344
TI  - [Legionellosis, a tourist problem?].
AB  - Legionellosis is a relatively rare disease characterized by an often prolonged
      and complicated course even in immunocompetent patients. Its diagnosis is
      mandatory for therapeutic and epidemiologic reasons. At the Kantonsspital Chur
      between 1998 and 2001, 6 cases of legionellosis have been observed: four of them
      were travel-associated and one concerned a local hotel employee. Due to the
      increasing international mobility epidemiologic investigations for the
      localization and elimination of the sources of infection are very difficult. A
      european task force, the European Working Group for Legionella Infections
      (EWGLI/www.ewgli.org) is addressing this problem. It is a matter of debate to
      what extent the public should be informed about sources of legionellosis (so
      called legionella hotels).

PMID- 12212345
TI  - [Value of radiological imaging after laparoscopic gastric banding].
AB  - Over the past years "laparoscopic gastric banding" has evolved to one of the
      leading surgical techniques for the treatment of patients with morbid obesity.
      Mainly two systems are used worldwide; the "LAP BAND" (ASGB--Adjustable Silicone
      Gastric Banding) and the "Swedish Band" (SAGB--Swedish Adjustable Gastric
      Banding) which may both be implanted laparoscopically around the proximal stomach
      at a suprabursal position, about 2 cm distally to the cardia, with the intention
      to create a small pouch and, therefore, to provide an earlier satiation. Both
      systems show only minor differences regarding their consistency and their opacity
      as well as regarding the volume of the system. However, the working mechanisms
      and the principal techniques of surgical implantation, luminal adjustment and
      management of postoperative weight loss as well as the way how to perform
      radiological controls in these patients are quite similar in both systems.
      Although these patients might be managed postoperatively by the clinicians alone,
      it has become well accepted over the past years that radiological controls are
      not only important for an exact luminal adjustment but crucial for the management
      of an ideal postoperative weight loss and for the detection of various
      postoperative complications. This article describes the radiographic appearances
      of both systems, instructs how to perform postoperative radiological controls in
      these patients and provides an overview of the known postoperative complications
      together with some recommendations regarding their therapeutic approach.

PMID- 12212346
TI  - [Prenatal stem cell transplantation and gene therapy in treatment of genetic
      diseases].

PMID- 12212347
TI  - [Delayed discovery of vertebral sarcoidosis].
AB  - Vertebral bone sarcoidosis is rare and may be difficult to diagnose. Clinical
      manifestations are often poor and the discovery can be fortuitous. We report a
      case of a 64 year old woman whose vertebral sarcoidosis diagnosis was established
      20 years after the primary discovery of a cured thoracic sarcoidosis.

PMID- 12212348
TI  - [53-year-old patient with over 38 degrees C fever over 3 weeks and generalized
      exanthema].

PMID- 12212349
TI  - Medical liability, putting the finger on the spot....

PMID- 12212350
TI  - Medical liability, the Order of Medical Doctors' point of view on the matter.

PMID- 12212351
TI  - Insurance of professional liability of physicians--specialists in hospitals.

PMID- 12212352
TI  - Ethics and medical liability: a minefield for physicians?

PMID- 12212353
TI  - [Transmission of examination results to patients: opinion of referring physicians
      and patients].
AB  - Patients frequently ask the nuclear medicine physician or the radiologist for
      conclusions at completion of a diagnostic procedure. The present study tried to
      assess opinions from both patients and referring physicians. Answers from both
      parties were grossly discordant: most of the referring physicians thought
      patients should not be given results of a diagnostic procedure by the nuclearist
      or radiologist an approach most of the patients disagreed with. Deontological
      guidelines of the official Belgian association do not authorize nuclear medicine
      physicians nor radiologists to give the patients any result directly; according
      to our data, this rule should be adapted.

PMID- 12212354
TI  - Clinical, biophysical and biochemical variables from African-heritage subjects
      with type 2 diabetes.
AB  - We compared the metabolic profile of two ethnic populations with type 2 diabetes,
      one from Bantu (n = 23; Ban) and the other from Belgian (n = 314) extraction
      followed at St Luc Hospital. Further comparison with a Belgian sub-cohort (n =
      64; Be) matched for age (52 yrs) and sex distribution (M/F: 61/39%) showed no
      significant difference between Belgian and Bantu subjects with regards to
      diabetes duration (9 and 11 yrs; Ban and Be respectively), age at diabetes
      diagnosis (43 and 42 yrs), HbA1c (8.1 +/- 1.9 vs. 8.5 +/- 1.9%; NS), and achieved
      education level. BMI was lower in Ban (29 +/- 4 vs. 32 +/- 7 in Be; p < 0.02), as
      were body fat (33 +/- 12 vs. 37 +/- 11 kg; NS) and waist diameter (99 +/- 9 vs.
      106 +/- 16 cm; p < 0.02). Forty-eight and 72% of Ban and Be were on metformin (p
      < 0.05), while insulin was given to 39 and 34%. Daily insulin dose was lower in
      Ban (0.31 +/- 0.20 vs. 0.47 +/- 0.18 IU.kg-1.24 h-1; p < 0.001). There was no
      difference in beta-cell function (% beta; normal: 100%) or insulin sensitivity
      (%S; normal: 100%) as determined with HOMA between groups. % beta (median [perc
      25-75]) was 51 [23-119] and 67 [45-84] in Ban and Be, while %S was 32 [29-37] and
      37 [27-45]. Smoking (past & current) prevalence was 5 and 47% in Ban and Be (p <
      0.0001). Prevalence of micro- and macroangiopathy did not differ between groups,
      although Ban had more macroalbuminuria (29 vs. 9%; p < 0.05), and were more often
      treated with Ca(2+)-channel- and beta-blockers than Be subjects (36 and 39% vs.
      16 and 8%; p = 0.07 and < 0.05, respectively). Fasting (F) and interprandial (IP)
      triglycerides (TG) were lower in Ban: 115 [81-149] vs. 189 [155-325] mg.dL-1 for
      F-TG and 127 [81-160] vs. 170 [128-305] mg.dL-1 for IP-TG (p < 0.0001), as was
      total cholesterol (201 +/- 53 vs. 223 +/- 40 mg.dL-1 (p < 0.05), despite lower
      use of hypolipidaemic drug (13 vs. 44%; p < 0.01). African-heritage subjects with
      type 2 diabetes have similar degree of diabetes control and complications, in the
      presence of leaner biophysical status, minimal tobacco exposure and lower fasting
      and interprandial triglycerides.

PMID- 12212355
TI  - Uveitis management: a multidisciplinary approach to assess systemic involvement
      and side effects of treatments.
AB  - OBJECTIVE: Non-infectious uveitis is often associated with systemic diseases
      severe enough to require corticosteroids (CS) and immunosuppressive drugs, which
      have potential serious side effects. METHODS: 28 patients with non-infectious
      uveitis were referred by the ophthalmologist. RESULTS: A systemic disease was
      found in 17/28 patients (60%): sarcoidosis in 11, spondylarthropathy in 3,
      Behcet's disease in 2, Crohn's disease in 1 patient. Eighteen patients received
      CS, 21 patients received immunosuppressive drugs. Most side effects were due to
      CS treatment: Cushing's syndrome in 12, cataract in 11, glucose intolerance in 3,
      gastric ulcus in 1, hypertension in 1, osteoporosis in 17, avascular bone
      necrosis in 3 patients. Prophylaxis or treatment of corticosteroids induced
      osteoporosis consists in calcium, 500 mg/day and vitamin D 400 IU in most of them
      with in addition hormone replacement therapy (n = 8) or bisphosphonates (n = 13).
      CONCLUSION: Sixty percent of patients with severe uveitis had a systemic disease.
      CS were the most deleterious drugs in spite of bi- or tri-therapy with CS sparing
      immunosuppressive drugs.

PMID- 12212356
TI  - [Hurthle cell thyroid carcinoma: report of 13 cases].
AB  - The aim of this study was to report the clinical characteristics of 13 patients
      with Hurthle carcinoma. In the vast majority of them, disease was suspected by a
      palpable thyroid nodule. The results of preoperative examination (scintigraphy,
      ultrasonography, thyroglobulin) are also discussed as well as the pathological
      aspects and follow-up characteristics after total thyroidectomy.

PMID- 12212357
TI  - Ileal perforation caused by cytomegalovirus infection in an immunocompetent
      adult.
AB  - A 71-year-old woman developed a small bowel perforation due to cytomegalovirus
      infection. She did not taken any immunosuppressive medication and her cellular
      immunity was normal. Surgical resection and antiviral therapy with ganciclovir
      led to complete recovery. As far as we know, this paper reports the first case of
      small bowel perforation due to cytomegalovirus infection in a non
      immunocompromised patient. Nevertheless the patient was known with diabetes
      mellitus. It should be emphasised that elderly patients have impaired immune
      defences and may be unsuspected hosts of opportunistic infections.

PMID- 12212358
TI  - Is the black thyroid really an innocuous pathological finding?
AB  - We report the case of a 24-year-old euthyroid woman in whom the discovery of a
      cold nodule in the left thyroid lobe led to a thyroidectomy. The surgical
      specimen was characterized by a diffuse black discoloration. Optical examination
      revealed brown granules within the apical portion of the follicular cells whereas
      ultrastructural studies showed intralysosomal lipofuscin-like deposits, all
      findings consistent with pathological descriptions reported in black thyroids
      associated with the intake of minocycline. Retrospectively, we were told that the
      patient had received this antibiotic for at least three years for the treatment
      of acne vulgaris. As experimental models have demonstrated potential antithyroid
      effects of the drug, it appears relevant to monitor thyroid tests in patients
      receiving long-term minocycline therapy.

PMID- 12212359
TI  - An artist's view of acromegaly.

PMID- 12212360
TI  - Hypertension and aneurysmal subarachnoid hemorrhage.

PMID- 12212361
TI  - Accidental deep hypothermia: a rewarming challenge.

PMID- 12212362
TI  - Short-chain fatty acids: bacterial mediators of a balanced host-microbial
      relationship in the human gut.
AB  - The luminal compartment of the gastrointestinal tract is colonized by a large and
      highly complex microflora providing not only nutritional advances, but also
      representing a potential immunological challenge for the host. Under
      physiological conditions, the immune cells of the colonic mucosa do not defeat
      the microflora. In contrast, in cases of inflammatory bowel disease (IBD), the
      intestinal microflora appears to be the target of immune reactivity as
      demonstrated in various genetic studies and animal models of mucosal
      inflammation. The mechanisms responsible for the maintenance of this
      immunological unresponsiveness in the mucosal compartment are still largely
      enigmatic though recent studies indicate that luminal components might control
      this peculiar state. The bacterial fermentation product n-butyrate has been
      identified as such as critical molecule. Apart from its essential nutritional
      function for colonocytes, an anti-inflammatory activity of this short-chain fatty
      acid (SCFA) has been recognized in vitro and in vivo. Regarding its molecular
      mode of action, an interference with transcription factors critical for the
      production of pro-inflammatory cytokines has been found. This overview discusses
      the physiological functions of this bacterial metabolite and its emerging role as
      a potent regulator of mucosal homeostasis. Special emphasis is laid on potential
      therapeutic implications of SCFA in the treatment of several forms of colitis.

PMID- 12212363
TI  - [Determination of glycated hemoglobins (Hb A1c)].
AB  - Glycated hemoglobin is measured as HbA1c and is the result of an irreversible non
      enzymatic glycation of the beta chain of hemoglobin A. HbA1c is used routinely to
      assess long term glycemic control in patients with diabetes mellitus. There are
      more than 20 determination methods, the techniques used are cation-exchange
      chromatography, electrophoresis, affinity chromatography and immunoassays,
      although each of these techniques measures a different fraction of the glycated
      hemoglobin. In addition, genetic hemoglobin variants and chemically modified
      derivates of hemoglobin can affect the HbA1c measurement and thus can not be
      included in international attempts for standardization. This manuscript reviews
      the current information on glycation of hemoglobin, HbA1c determination methods,
      interferences and attempts for standardization. We aim at pointing out to the
      reader the current problems of glycated hemoglobin determination and to describe
      the necessary measures which need to be taken for proper measurement of HbA1c.

PMID- 12212364
TI  - A case of purple urine bag syndrome (PUBS).

PMID- 12212365
TI  - Is hypertension a major risk factor in aneurysmal subarachnoid hemorrhage?
AB  - OBJECTIVE: The role of hypertension as a major risk factor for the development
      and rupture of cerebral aneurysms is a subject of considerable debate. METHODS:
      In order to substantiate or weaken the hypothesis of the atherogenic,
      degenerative origin of this disease, in addition to hypertension the influence of
      smoking and the covariates body weight, hematocrit, fibrinogen and leukocrit were
      examined in a hospital-based case-control and cohort study. 141 consecutive
      patients with subarachnoid hemorrhage (SAH) and verified cerebral aneurysms,
      admitted between September 1994 and August 1998, were investigated. RESULTS: An
      association was found between hypertension and SAH of cerebral aneurysm in the
      entire patient group (P < 0.0001). In the stepwise logistic regression, the
      exposure odds ratio (OR) for hypertension was 6.8 (CI (95%): 3.53-13.14). Smokers
      have a twofold higher risk, with an OR of 2.2 (CI (95%): 1.19-4.06). Age was
      found to have a prognostic impact on the disease (P = 0.0089). Age obviously was
      a confounding factor for hypertension, which was associated with the outcome (P =
      0.048). CONCLUSION: Patients with hypertension had a nearly seven-fold higher
      risk of aneurysmal subarchnoid hemorrhage. This seems to substantiate the
      hypothesis that aneurysm is an acquired and hemodynamically induced chronic
      disease.

PMID- 12212366
TI  - Severe accidental hypothermia with or without hemodynamic instability: rewarming
      without the use of extracorporeal circulation.
AB  - BACKGROUND: The optimal rewarming technique for patients in deep accidental
      hypothermia with core temperatures below 28 degrees C is not established. Several
      authors believe that extracorporeal rewarming is essential, especially for
      patients with hemodynamic instability. Others believe that invasive rewarming
      ought to be reserved for patients in cardiac arrest. We describe our experience
      with a strictly conservative technique without the use of invasive rewarming
      devices in patients with severe accidental hypothermia and a sustained perfusion
      rhythm. METHODS: A cohort study extending from 1991 to 2000, including all
      patients received at the emergency department of the University Hospital of
      Vienna with severe hypothermia, a core temperature of maximum 28 degrees C and no
      preclinical cardiac arrest. RESULTS: 36 patients with deep hypothermia were
      included in the study. Their core temperatures ranged from 20.2 degrees C to 28
      degrees C; the median temperature was 25.75 degrees C (25th and 75th percentile,
      24.2/27.3). Fourteen patients were intoxicated and their multimorbidity was high.
      All of 19 patients with stable hemodynamics and 14 of 17 patients with unstable
      hemodynamics were successfully rewarmed to normothermia with warmed infusions,
      inhalation rewarming and forced air rewarming. The rewarming process took 9.5
      hours (8/10.5) and required a volume load of 4820 ml (2735/5770). The rewarming
      rate was 1.09 degrees C per hour (0.94/1.25). Although 92% of the patients were
      successfully rewarmed to normothermia, in-hospital mortality was 42%, but was
      largely related to comorbidity. DISCUSSION: A conservative approach is highly
      successful in achieving normothermia in patients with deep hypothermia with or
      without stable hemodynamics. In-hospital mortality of severe accidental
      hypothermia in urban conditions is high; comorbidity might play a major role. The
      influence of the rewarming strategy on late in-hospital mortality remains
      unclear.

PMID- 12212367
TI  - Insulin resistance and androgens in healthy women with different body fat
      distributions.
AB  - OBJECTIVE: To compare androgens and sex hormone-binding globulin (SHBG) levels,
      and indices of insulin sensitivity (the response of plasma insulin and C-peptide
      in OGTT, insulin resistance and beta-cell activity estimated with the homeostasis
      assessment model (HOMA model) in healthy obese premenopausal women with different
      body fat distributions. PATIENTS AND METHODS: Free testosterone, androstenedione,
      SHBG levels and responses of plasma glucose, insulin and C-peptide in OGTT were
      examined in 74 healthy premenopausal women (19 with lower-body obesity (WHR <
      0.80), 20 with pure abdominal obesity (WHR > 0.85), 19 with predominant abdominal
      obesity (WHR 0.81-0.85) and 18 normal-weight women). Insulin resistance and beta
      cell function were estimated with the HOMA model. RESULTS: Both fasting and
      glucose-induced insulin levels were higher in women with pure abdominal obesity
      than in the controls (p < 0.001) and in those with lower-body obesity (P < 0.01).
      Insulin resistance was also higher in women with pure abdominal obesity than in
      the controls (p < 0.01) and those with lower-body obesity (p < 0.05). Free
      testosterone (p < 0.01) was higher and SHBG (p < 0.001) was lower in women with
      abdominal obesity than in the control group and those with lower-body obesity.
      Insulin significantly correlated with SHBG, and this correlation was independent
      of androgens, obesity and obesity type. Beta-cell function positively correlated
      with free testosterone, whereas insulin resistance negatively correlated with
      SHBG, and was independent of obesity and obesity type. CONCLUSIONS: In healthy
      premenopausal women, increased BMI and more pronounced abdominal fat accumulation
      was associated with increased androgenic activity (higher free testosterone and
      lower SHBG levels) and with insulin resistance estimated using the HOMA model, as
      well as with increasing basal and glucose-induced insulin levels. SHBG levels
      correlated with insulin and insulin resistance independently of the degree of
      obesity, obesity type and androgens, whereas beta-cell function correlated only
      with free testosterone.

PMID- 12212368
TI  - Duplex sonographic predictors of restenosis, vascular and neurological events
      after carotid endarterectomy.
AB  - BACKGROUND: Although excellent short- and long-term results have been achieved
      with surgery in extracranial internal carotid artery stenosis, recurrent stenosis
      continues to play an important role in post-endarterectomy. Therefore, a close
      follow-up of patients is warranted. The value of postoperative duplex sonographic
      evaluations in postoperative follow-up is highly disputed. The study evaluates
      duplex sonographic parameters as predictors of carotid restenosis, general
      vascular events and ipsilateral neurological symptoms, in order to assess the
      role of duplex sonography in follow-up after carotid endarterectomy. METHODS: A
      retrospective cohort study with a follow-up period ranging from 7 months to 7.5
      years was performed in 150 patients who underwent carotid endarterectomy. Pre-
      and postoperative duplex sonographic and clinical data were analyzed by life
      table analysis and multivariate Cox regression with respect to carotid
      restenosis, vascular and ipsilateral neurological events. MAIN FINDINGS: Duplex
      sonographic predictors of carotid restenosis include the postoperative degree of
      stenosis (residual stenosis > or = 30% or more: relative risk (RR) = 1.56; 1.05
      2.32), pre- to postoperative reduction of stenosis (higher than 50%: RR = 0.61;
      0.45-0.83), and residual plaques in the operated carotid artery (RR = 1.96; 1.31
      2.93). Some of these morphological parameters such as reduction of stenosis are
      also predictive of vascular events (RR = 1.25; 1.01-1.56) and ipsilateral
      neurological events (RR = 1.52; 1.05-2.19). In 12 cases restenosis was discovered
      by duplex sonography and in 3 cases by evaluation of clinical symptoms. In 5
      cases restenosis was treated by repeat surgery. Contralaterally, progressive or
      newly developed carotid stenoses were observed in 17 cases, and only 5 were
      discovered on the basis of clinical symptoms. Fourteen contralateral stenoses
      required surgery. Overall, 12 patients underwent treatment for stroke prevention
      on the basis of duplex follow-up findings (8% of the study population).
      CONCLUSIONS: Postoperative duplex sonography allows for the identification of
      patients at risk for carotid restenosis as well as those at risk for other
      vascular events. As expected, regular examinations permit early detection of
      restenosis requiring surgical treatment. However, a large number of contralateral
      stenoses requiring surgical treatment were detected by routine duplex sonographic
      examinations. The timing of follow-up intervals may be oriented towards the
      perioperative outcome of duplex sonography.

PMID- 12212369
TI  - [Frontal lobe epilepsy--clinical seizure seminology].
AB  - The aim of this study was an analysis of the localizing and lateralizing value of
      clinical symptoms in frontal lobe epilepsy. Nineteen patients with medically
      refractory seizures originating from the frontal lobe were examined
      retrospectively, seven of these patients underwent subsequent neurosurgical
      removal of the epileptogenic zone. The predominant clinical symptoms were clonic
      (53%) and tonic motor phenomena (89%). Dystonic posturing (32%) and postictal
      paresis (37%) occurred frequently, indicating a seizure onset in the
      contralateral hemisphere. Head version contralateral to the seizure onset zone,
      as demonstrated in 53% of the patients, was a reliable lateralizing sign, whereas
      early head and eye turning (11%) had no lateralizing significance. 37% of the
      patients showed ictal vocalisation, another 37% presented with automatisms--so
      called hypermotor seizures should be considered as a special subtype. An aura was
      present in 26% of the patients--in most cases as a somatosensory manifestation or
      a feeling of dizziness, especially with seizures originating from the
      supplementary motor area (SMA) or the precentral area. Secondary generalization
      and seizure series occurred frequently. Unilateral automatisms, head version,
      tonic phenomena, dystonic posturing, unilateral grimacing, postictal paresis and
      unilateral clonic movements could be identified as reliable lateralizing signs.
      We conclude that the analysis of clinical symptoms plays an important role in
      presurgical epilepsy diagnosis.

PMID- 12212370
TI  - [SAPHO syndrome: case report of an 18-year-old man and review of the literature].
AB  - We report about an 18-year-old man, suffering from acne on his face and trunk and
      complaining about indefinite bone pains--without any trauma. SAPHO-syndrome was
      diagnosed which consists of synovitis, acne, pustulosis, hyperostosis and
      osteitis. Five types of this syndrome can be differentiated: spondarthritis
      hyperostotica pustulo-psoriatica, chronic recurrent multifocal osteomyelitis,
      inflammatory chest wall syndrome, isolated sternocostoclavicular hyperostosis,
      and the combined form of acne-associated spondarthritis and chronic recurrent
      osteomyelitis. Although the sapho-syndrome is very rare, it should be considered
      a possible diagnosis in the case of indefinite bone pains in combination with
      acne, pustulosis and hyperostosis.

PMID- 12212371
TI  - Calcific trochanteric bursitis: resolution of calcifications and clinical
      remission with non-invasive treatment. A case report.
AB  - Calcific trochanteric bursitis, a common regional pain syndrome, is characterized
      by chronic, intermittent aching pain over the lateral aspect of the hip and
      limitation of function. Effective treatment is invasive, including infiltration
      therapy and surgical intervention. The therapeutic effects of conservative
      treatment modalities have not been proven. A 59-year-old woman presented at the
      department of physical medicine and rehabilitation with a 2-year history of pain
      in the right hip. She had been treated with several agents such as
      glucocorticoids and local anesthetics (via injection) for two years, but without
      success. Physical examination revealed the clinical diagnosis of bursitis
      trochanterica. Radiographic findings showed calcified rounded masses measuring
      about 1.5 cm in diameter around the greater trochanter; a calcific bursitis
      trochanterica was diagnosed. The patient presented for conservative treatment in
      order to avoid surgical intervention for removing the calcification and the
      bursal sac. A non-invasive treatment regimen including intensive pulsed
      ultrasound therapy, physiotherapy and iontophoresis was started. The conservative
      treatment led to a remission of both, symptoms as well as radiographic findings,
      which revealed complete resolution of calcifications. This case report shows
      that, in cases of calcific trochanteric bursitis (including those with extensive
      calcifications), a non-invasive conservative treatment regimen including
      intensive high-dosed pulsed ultrasound therapy should be attempted before more
      invasive treatment (injections, surgery) is considered.

PMID- 12212372
TI  - [Neutrophilic respiratory response in surgical infection and an association with
      plasma membranous synthesis of ATP].
AB  - Early studies have demonstrated that the unique phenomenon ATP aerobic synthesis
      on neutrophilic plasma membranes is observed when neutrophils are activated with
      the chemoattractive peptide FMLP. This paper presents the results of the study of
      a possible association of ATP plasma membranous synthesis with priming, with the
      occurrence of respiratory explosion and apoptosis of the neutrophils isolated
      from the blood of donors and patients with surgical infection of different
      severity. The interaction of neutrophilic plasma membranes with FMLP and with
      hTNF (was attended by ATP synthesis. Examining the level of FMLP-stimulated
      production of superoxide in patients with surgical infection revealed that the
      amount of the superoxide produced by neutrophils noticeably decreased and
      droppped by more than 5 times in sepsis. The FMLP-stimulated plasma membranous
      synthesis of ATP was determined in the same patients. A decrease in the
      production of superoxide was simultaneously accompanied by a reduction in the
      plasma membranous synthesis of ATP. Both the plasma membranous synthesis of ATP
      and the production of superoxide declined in sepsis at the most. The neutrophils
      isolated from peripheral blood of the same patients showed DNA damage whose
      degree was directly related to the condition of a patient. The maximum DNA
      damages were observed in sepsis. The findings suggest that apoptosis is induced
      in surgical infection in the peripheral neutrophils. The DNA damage and the FMLP
      stimulated plasma membranous synthesis of ATP was estimated in the neutrophils
      isolated from the inflammation focus. It turned out that in local surgical
      infection, there were the maximum DNA damages and the FMLP-stimulated plasma
      membranous synthesis of ATP was lower than that in the peripheral neutrophils. It
      can be suggested that the FMLP-stimulated plasma membranous synthesis of ATP may
      be a regulators of neutrophilic functional states in surgical infection and
      sepsis.

PMID- 12212373
TI  - [Impact of blood loss on lipid peroxidation and on the antioxidative system in
      victims with isolated injury to the chest and abdomen].
AB  - The paper deals with the impact of the volume of blood loss on the time course of
      changes in the parameters of lipid peroxidation (LPO) and the antioxidative
      system (AOS) in the sera of 22 and 31 victims with isolated chest and abdominal
      injuries, respectively, on days 1, 3, 7, and 14 days after injury. All the
      victims were found to have enhanced LPO processes and altered AOS. The severity
      of disorders in the LPO-AOS system depends on the size of blood loss, the
      disorders manifest themselves to a greater extent with over 2-liter brisk
      bleeding and enhance on days 7 and 14 after injury. In mild blood loss equal to
      as low as 1.0 liters, there was a mobilization of AOS components, such as (
      tocopherol and ceruloplasmin, to the blood bed in the victims with both isolated
      chest and abdominal injury. AOS failure remaining during all periods of the study
      was detected in victims with abdominal organs and over 2-liter blood loss.
      Disorders in the LPO-AOS system were pronounced in abdominal injury.
      Multimodality treatment in victims with isolated injury of the chest and abdomen
      does not normalize impaired LPO processes and AOS, which makes it necessary to
      include into antioxidative therapy for brisk bleeding.

PMID- 12212374
TI  - [Cardiac damage and protection in acute fatal blood loss].
AB  - Experiments on dogs and albino non-inbred male rats undergone a 4-5-min clinical
      death under the conditions of the whole organism and isolated isovolumetric
      contracting heart revealed phasic systemic hemodynamic and myocardial contractile
      disorders. The leading pathogenetic factors of postresuscitational cardiac damage
      are excessive catecholamine stimulation of cardiac beta-adrenoreceptors, impaired
      energy metabolism, excessive activation of free radical processes, metabolic
      acidosis, secondary hypoxia, and endogenous toxemia. The heart was found to be at
      the most damaged within the first hour after resuscitation. The use of
      antihypoxants, antioxidants, beta-adrenoblockers and Ca-channel blockers were
      pathogenetically substantiated to diminish postresuscitational cardiac damages.

PMID- 12212375
TI  - [Enzymemia: an adaptive mechanism of a marker of cytolysis?].
AB  - The data available in the literature and the authors' own findings on possible
      causes, mechanisms, and modes of enzyme appearance in the blood are analyzed.
      Blood enzymes has been ascertained to play a major role in maintaining the body's
      metabolism. Clinical and experimental findings make it possible to conclude that
      it is biologically expedient for enzymemia to develop both in pathology and that
      blood enzymes are in the normal range.

PMID- 12212376
TI  - [Neurophysiological analysis of the effects of antihypoxic versus psychotropic
      agents].
AB  - The Fourie EEG spectral analysis of thr sensomotor cortex and dorsal hypocampus
      in freely moving rats could reveal the common pharmacological EEG effects of
      different antihypoxic agents (gutimin, amtizole, emoxipine, and 3-OPK). All the
      agents decreased the total EEG power (they all reduced the absolute power in all
      frequency bands) and simultaneously enhanced (2 relative power. The former
      suggests that there was a decrease in the energetic level of bioelectric
      fluctuations, which may indicate that the brain reduces its energetic functioning
      level. The latter means that antihypoxic drugs activate the central nervous
      system. This effect may normalize EEG activity during hypoxic conditions, which
      causes the enhancement of slow-wave activity and reduces fast EEG activity. The
      pharmacological EEG effects of different groups of psychotropic drugs (nootropic
      drugs, psychostimulants, antidepressants, benzodiazepine tranquilizers, etc.)
      versus antihypoxants are discussed.

PMID- 12212377
TI  - [The intestinal microenvironment in healthy persons under the technogenic action
      of an industrial city].
AB  - The intestinal microflora was studied in 806 healthy persons residing in three
      different environmental areas of the city of Volgograd. The study indicated that
      there were qualitative and quantitative differences in its composition, the
      heterogenicity of microbiocenosis being due to the degree of ambient air
      pollution. The changed found allowed four cenotypes (normal variants) of the
      microflora to be identified in urban residents. As the technogenic burden was
      ascertained to increase on the population, there was a rise in the incidence of
      atypical variants of the microflora, which were detectable at a rate of 30.6% in
      the ecologically good central area whereas their rates were 63.3 and 74.9% in
      both a northern and a southern areas where the basic enterprises of chemical and
      metallurgic industries are located.

PMID- 12212378
TI  - [Molecular genetic characteristics of HIV-1 in Russia].
AB  - The paper presents data on the variants of human immunodefficiency virus type 1
      (HIV-1) currently circulating in Russia. The subtype A HIV-1 variant dominating
      is shown to be most widespread among drug-injected users in the most regions
      under study. By using the results of an analysis of 1,464 blood samples taken in
      the past 4 years in 69 subjects of the Russian Federation, the authors have
      estimated that this HIV-1 variant is responsible for 93% of all HIV-infection
      cases in the country. The greatest regional genetic diversity was observed in
      Moscow and its mean (2.35(1.59) was found to be comparable to that (2.41(1.85) in
      the whole country. Penetration of the subtype A IV-1 variant early detectable
      among drug-users into other risk groups was noted.

PMID- 12212379
TI  - [Collaborating scientific centers are the important form of partnership between
      the Russian Academy of Medical Sciences and the World Health Organization].

PMID- 12212380
TI  - [Mechanisms of bioactivation of xenobiotics under the influence of enzymatic
      systems of the body].

PMID- 12212381
TI  - [Oxidative stress in bacteria].

PMID- 12212382
TI  - [L. A. Orbeli and Russian physiology (On the occasion of the 120th birthday)].

PMID- 12212384
TI  - HIV: the fight for equal treatment.

PMID- 12212383
TI  - [Serotonin and serotonin receptors in the genesis of stress and adaptation].
AB  - The paper presents a current concept of the genesis of stress and adaptation with
      regard to new data on serotonin and its receptors. There is evidence that stress
      is transient hypoxia that results from dysfunction of smooth muscles (SM) in the
      microcirculatory bed (a pharmacological stage) with partial or complete
      dysfunction of the organ or system where dysfunction has occurred (a clinical
      stage). Impaired interaction of serotonin with GM serotonin receptors, which
      occurs with excess serotonin receptor ligands due to various stress factors,
      underlie the pharmacological and clinical manifestations of stress. The
      occurrence of transient hypoxia is followed by the activation of antistress
      (adaptive) processes in the organism with thrombocytic release of serotonin. In
      endogenous hyperserotoninemia, microcirculation improves, a hypoxic area ceases,
      and/or damaged and necrotic tissues localize. With this, endogenous serotonin
      induced recovery of different organs is the essence of an adaptive process.
      Clinical and experimental evidence suggesting that exogenous serotonin
      administration just simulates an elevation in the concentration of endogenous
      serotonin as a material substrate of the human adaptive system.

PMID- 12212385
TI  - Sense of touch. Interview by Judy Czylok.

PMID- 12212386
TI  - Senior nurses' control expectations and the development of pressure ulcers.
AB  - AIM: The aim of this research was to establish whether the attitudes and
      expectations of senior nursing staff might adversely affect patient outcomes in
      the prevention of pressure ulcers. The hypothesis was that nursing locus of
      control affects clinical outcomes in patients. In particular, it affects
      departmental prevalence of pressure damage. METHOD: A population of nurses (n =
      439) in an acute and community NHS trust were surveyed to test knowledge, control
      beliefs and value of pressure ulcer prevention relative to prevalence. The
      research was designed to provide different data against which to test the
      hypothesis: first, to assess acceptability of nurses' knowledge of prevention and
      appropriate use of risk assessment and equipment; second, to calculate a mean
      departmental pressure ulcer prevalence; and third, to measure locus of control
      and value, which is the focus of this article. RESULTS: There were strong
      associations between departmental prevalence of pressure ulcers and attitudes of
      senior nursing staff. For example, the more that ward sisters believed they could
      control pressure ulcer prevention, the higher the prevalence of ulcers in their
      department. The more that sisters believed that they could not control
      prevalence, the lower the prevalence of ulcers. CONCLUSION: The study shows that
      failure to account for beliefs, values and expectations of staff could lead to
      patient harm. It is suggested that it might be counterproductive to put great
      effort into developing clinical guidelines and refinement of risk assessment
      methods. The findings have important implications for nursing, and challenge the
      assumption that nurse leaders are universally beneficial to patients.

PMID- 12212387
TI  - Bullying in nursing.
AB  - BACKGROUND: Current concerns about the need to improve the working lives of
      health service staff are well founded, and are receiving new impetus in current
      NHS human resource practice. However, the incidence of bullying in nursing would
      seem particularly problematic considering its effect on such a large proportion
      of the health service workforce. This article deals with a number of pertinent
      issues regarding what might constitute bullying and the growth of the phenomenon.
      In particular, the lessons we can learn in relation to its impact on patient care
      should be of concern. CONCLUSION: Ongoing research by the author is beginning to
      indicate that managerial and often union recognition and handling of such
      problems is frequently far from satisfactory. The article concludes with some
      suggestions for improvements.

PMID- 12212388
TI  - Skin cancer.
AB  - The incidence of skin cancer is increasing and nurses are in an ideal position to
      help patients prevent and identify the disease at an early stage.

PMID- 12212389
TI  - Under new management.

PMID- 12212390
TI  - Ending it all.

PMID- 12212391
TI  - Sex talk.

PMID- 12212392
TI  - Best foot forward.

PMID- 12212393
TI  - Complying with pelvic floor exercises: a literature review.
AB  - In this literature review the causes and factors predisposing women to stress
      urinary incontinence and the role of pelvic floor muscle exercises in curing and
      reducing the severity of symptoms are examined. Research on compliance with the
      recommended exercise regimen is reviewed to explore what factors might influence
      compliance with this regimen and how nursing staff can seek to optimise
      compliance in future.

PMID- 12212394
TI  - Learning disabilities: the need for better health care.
AB  - There is broad acknowledgement within services for people with learning
      disabilities that the general health of this client group is poor. There is an
      impressive body of published research to demonstrate why these problems exist
      within the population receiving care in the community. Initiatives outlined in
      the White Paper Valuing People: A New Strategy for Learning Disability for the
      21st Century (DoH 2001) to develop individual health action plans and provide
      health facilitators give an excellent opportunity to remedy this situation and
      make a difference to the health and quality of life for people with learning
      disabilities.

PMID- 12212395
TI  - A philosophical analysis of informed consent.
AB  - In this article, Stephen Booth analyses the concepts of informed consent and
      competence. He also examines the conditions necessary for consent to be valid.

PMID- 12212396
TI  - International travel and health assessment.
AB  - Travel risk assessment is an essential component of travel consultation, and is
      an efficient way of providing international travellers with evidence-based
      advice.

PMID- 12212397
TI  - Making the move.

PMID- 12212399
TI  - [Results of a health education program on smoking for trainee workers].
AB  - BACKGROUND: Social costs of smoking behaviour are remarkable. Although smoking is
      an individual choice, it is strongly influenced by a social contest where it is
      widespread. OBJECTIVES: To induce young non-smoking apprentices to continue as
      such and smokers to give up smoking. METHODS: During 1999, a specific health
      education programme on smoking was carried out for a group of 1083 young
      apprentices, 531 females and 552 males, who came to the occupational health unit
      in Venice for a check on work fitness. This programme was part of a larger global
      programme concerning health hazards prevention where apprentices received various
      information about health and safety at work. Smoking habits were compared to a
      control group of 312 females and 458 males after a one year follow-up. RESULTS:
      The females' chance of giving up smoking was three times higher than controls;
      while the chance of becoming a smoker was 70% lower. The males' chance of giving
      up smoking was double; while the chance of becoming a smoker was 60% lower. The
      health education programme decreased the trend of becoming a smoker in cases and
      increased non-smoking, especially in females. In females, there was also a
      significant prevalence who reduced cigarette consumption. CONCLUSIONS: This study
      demonstrates the effectiveness of health education programmes on smoking directed
      to young people and stresses the role of public health units in the involvement
      of the users of such services in prevention programmes. An occupational health
      service has specific prevention objectives here, since promoting healthy
      attitudes affects motivation of individual behaviour. This is the reason why
      initiatives on a single specific prevention objective, like smoking, become
      significant in every context of people's lives. Such attitudes are a significant
      resource which people can use to protect themselves from hazards, with a
      resulting safe, aware and active behaviour as regards occupational risks.

PMID- 12212398
TI  - Occupational risk factors for renal cell cancer. An Italian case-control study.
AB  - AIM: To examine possible associations between occupational and environmental risk
      factors and renal cell cancer (RCC), a tumour with unclear aetiology and
      increasing incidence. METHODS: A questionnaire-based case-control study of 100
      histologically verified cases of RCC and 200 controls was conducted at Parma
      University Hospital. The control group was enrolled from patients attending
      different outpatient departments and represented the same residential area as the
      cases. For all exposure variables under study, two levels of duration were
      defined: "short" and "prolonged" for less than 10 years or more, respectively.
      RESULTS: The highest risk estimates for RCC were found for "prolonged" exposure
      to organic solvents with an odds ratio (OR) of 2.2 (95% confidence interval, CI:
      1.0-4.8). "Prolonged" exposures to pesticides and copper sulphate were also
      associated with increased risk, OR 2.0 (95% CI: 0.8-4.7) and OR 2.7 (95% CI: 1.3
      5.5), respectively. CONCLUSIONS: Our data suggests an association between RCC and
      exposure to organic solvents, pesticides and copper sulphate. A risk gradient as
      a function of exposure duration was found for organic solvents (p = 0.044) and
      copper sulphate (p = 0.036), but not for pesticides.

PMID- 12212400
TI  - Hepatitis B vaccination awareness and biological risk.
AB  - BACKGROUND: Hepatitis B virus is a possible risk in persons exposed to biological
      risk at work. Vaccination is the only prevention against infection. OBJECTIVES: A
      population of 1,408 employees of the University of Padua was investigated to
      define the immunological status for HBV and degree of awareness to hepatitis B
      vaccination. METHODS: The subjects were subdivided according to sex, age (< or =
      40 or > 40 years old), level of education (college graduates or lower), and the
      extent of biological risk (no risk, low or high risk). Clinical history
      questionnaires were used and measurement of hepatitis B markers was carried out.
      RESULTS: The results showed that only 30.5% of the subjects had been vaccinated;
      among these, 90.2% showed a measurable level of anti-HBs antibodies, 8.2% showed
      anti-HBs antibodies lower than 10 IU/L, and 1.6% showed positive markers of
      previous infection. However, among non-vaccinated subjects 13.4% were positive
      for previous infection; in all subjects, prevalence of hepatitis B virus
      infection was 9.8%. The awareness to hepatitis B vaccination was altogether very
      low (30.5%), but females (44.2%), subjects less than 40 years of age (43.5%),
      college graduates (34.1%), and high risk exposed personnel (57.7%) were more
      likely to comply compared to male subjects (odds ratio 2.53), subjects more than
      40 years of age (odds ratio 3.57), non-college graduates (odds ratio 1.65), or
      low risk exposed (odds ratio 13.42). CONCLUSIONS: The variables considered
      appeared to influence awareness to vaccination. Owing to low awareness, an
      information campaign was started and 90% of the invited subjects were immunized.

PMID- 12212401
TI  - [Cognitive sequelae of acute hydrogen sulphide poisoning. A case report].
AB  - BACKGROUND: Hydrogen Sulphide (H2S) is a highly toxic, colorless gas smelling of
      rotten eggs. It is used in several industries and is a product of many industrial
      processes such as oil refining, mining and rayon manufacture. Acute, non fatal
      H2S intoxication at a concentration of 500 ppm, for few minutes, is followed by
      brain damage characterised by both immediate and permanent neurobehavioural
      deficits. OBJECTIVES: The present study describes the neurobehavioral effects of
      acute, non-fatal H2S intoxication in a healthy 36-year-old male at the workplace.
      METHODS: Three months after the acute poisoning, the subject was examined via a
      neurological examination, neuropsychological tests (Mini Mental State, Verbal
      Span Test, Digit Span Test, Bourdon-Wiersma Dot Cancellation Test, Benton Visual
      Retention Test, Somatognosia, Simple Visual Reaction Time, Simple Acoustic
      Reaction Time), Nuclear Magnetic Resonance (NMR), and Single Photon Emission
      Tomography (SPET). RESULTS: The results showed a reduction of cognitive
      capabilities, depressive symptoms and personality changes even through the
      results of neurological examination and neuroimaging techniques were
      unremarkable. CONCLUSIONS: Neuropsychological testing is a key issue in
      neurotoxicology assessment, because conventional neurology has been shown to be
      insensitive to the chemical neurotoxic effects and neuroimaging techniques are
      often unclear.

PMID- 12212402
TI  - [Mental health and work environment of a group of public health preventive
      service users].
AB  - BACKGROUND: In a previous organizational study we proposed shared technical
      initiatives in public occupational health and mental health public services
      dedicated to mental health at work which is now completely neglected. OBJECTIVES:
      To study the occupational mental health demand in public health services users by
      improving shared tools among public health services. METHODS: Data collection on
      socio-demographic characteristics, relationship between mental health and working
      environment, organizational constraints in a group of mental, occupational and
      public health service users (no 90). RESULTS: A third of the users, mostly women,
      described the working environment as negative for mental health. The main
      reported organizational constraints were poor career possibilities, relationship
      with the public and workload. Inadequate workload is the leading cause for a
      negative evaluation of working conditions for mental health. CONCLUSIONS: This
      study confirms that mental health at work is a public health problem that has to
      be better investigated using tools shared between mental and occupational health
      services.

PMID- 12212403
TI  - Knowledge, attitudes and practices (KAP) among agricultural extension workers
      concerning the reduction of the adverse impact of pesticides in agricultural
      areas in Tanzania.
AB  - BACKGROUND: Extension workers are educated locally to enable them to train
      farmers in using improved local farming methods and imported technology, such as
      pesticides, to increase crop production. However, the extension workers are not
      adequately trained in health aspects of pesticides and hence are unable to
      provide adequate services to farmers with regard to safe use of pesticides.
      OBJECTIVE: The present study assessed the knowledge, attitudes and practices of
      agricultural extension workers with respect to health effects of pesticides in
      order to develop strategies for the control of pesticide exposure and prevention
      of pesticide poisoning in Tanzania. METHODS: A survey of Tanzanian agricultural
      extensionists was undertaken in 1991-1994 using a standardized questionnaire in
      face-to-face interviews. Extensionists who were district agricultural officers,
      assistant agricultural officers, agricultural assistants, and field assistants,
      working in the coffee and cotton growing areas (N = 61) within a radius of 15 km
      of farm, estate or village under farm worker study (reported elsewhere) were
      included in the survey. RESULTS: The majority of extensionists knew that
      pesticides could enter the human body but only a quarter perceived pesticides as
      a major problem in the community they served. The majority showed awareness of
      potential health hazards of the different pesticides used in their service areas,
      but they did not recognize what pesticides were responsible for poisoning. A high
      proportion was familiar with first aid procedures in case of pesticide poisoning;
      however, many procedures described were not appropriate for pesticide poisoning.
      CONCLUSIONS: The survey indicated that training of agricultural workers in health
      aspects of pesticide exposure is an important task for adequate provision of
      service to farmers with regard to safe use of pesticides in Tanzania.
      Nevertheless, the appropriate role of extensionists in reducing the health impact
      of pesticides would be to advocate pesticides of low toxicity or non-chemical
      pest control.

PMID- 12212405
TI  - [Concerning the celebration of the centenary of the "Luigi Devoto" Clinica del
      Lavoro of Milan].

PMID- 12212404
TI  - [Risk of hepatitis C in health personnel].

PMID- 12212406
TI  - Effectiveness of a school-based intervention at changing preadolescents' tobacco
      use and attitudes.
AB  - This study evaluated the effectiveness of a tobacco intervention on
      preadolescents' tobacco use and attitudes. A tobacco assessment questionnaire was
      distributed to seventh-grade students in May 1997 (N = 229) and 1999 (N = 230).
      During the 1998-1999 academic year, sixth-grade students at the intervention
      school received a tobacco intervention. Though not statistically significant, the
      number of smokers at the intervention school decreased from 43.2% to 31.1% after
      the intervention (p = .09). These students predicted less smoking in five years
      (29.6% to 19.8%, p = .078) and 20 years (28.4% to 13.2%, p = .004). Because of
      the difficulty in reducing smoking rates at the population level, the
      nonsignificant results can be viewed as a success rather than a setback. When
      faced with increasing use trends, an intervention can at least hope to achieve a
      decrease or slow the rate of growth, and the program succeeded in that respect.
      School-based interventions can effectively influence preadolescent' attitudes
      concerning tobacco use. Future programs should begin earlier and be reinforced
      yearly.

PMID- 12212407
TI  - Factors in the school cafeteria influencing food choices by high school students.
AB  - This study set three objectives: 1) to examine the perceived influence of health
      concerns, labeling and nutrition information, taste, cost, availability, and
      peers on adolescents' food choices, particularly in the school cafeteria; 2) to
      determine whether these factors vary by gender, grade level, or adolescents'
      health and weight concerns; and 3) to provide recommendations regarding promotion
      of low-fat foods in the school cafeteria based on factors associated with food
      choices. Data were collected from a school survey that assessed key influences on
      adolescents' food choices, including low-fat foods. Some 289 students in grades
      10-12 from a senior high school in a metropolitan area served as subjects.
      Descriptive statistics, chi-square, and general linear models were used for
      analysis. Results indicated that, when choosing foods from the school cafeteria,
      taste and getting a lot for their money were important to most students (93.7%
      and 71.7%, respectively). Females, and students who thought about their health
      and weight more frequently when deciding what to eat, were more likely to report
      greater interest in labeling and nutrition information and availability of low
      fat foods in the school cafeteria. Findings suggest that efforts to promote low
      fat foods to adolescents need to address the taste of low-fat foods, availability
      of low-fat options, and point-of-purchase labeling of low-fat foods. Focusing on
      the value and cost of low-fat foods may offer a key strategy for promoting low
      fat foods to males.

PMID- 12212408
TI  - Participant satisfaction with a school telehealth education program using
      interactive compressed video delivery methods in rural Arkansas.
AB  - Socioeconomic and demographic factors can affect the impact of telehealth
      education programs that use interactive compressed video technology. This study
      assessed program satisfaction among participants in the University of Arkansas
      for Medical Sciences' School Telehealth Education Program delivered by
      interactive compressed video. Variables in the one-group posttest study were age,
      gender, ethnicity, education, community size, and program topics for years 1997
      1999. The convenience sample included 3,319 participants in junior high and high
      schools. The School Telehealth Education Program provided information about
      health risks, disease prevention, health promotion, personal growth, and health
      sciences. Adolescents reported medium to high levels of satisfaction regarding
      program interest and quality. Significantly higher satisfaction was expressed for
      programs on muscular dystrophy, anatomy of the heart, and tobacco addiction (p <
      0.001 to p = 0.003). Females, African Americans, and junior high school students
      reported significantly greater satisfaction (p < 0.001 to p = 0.005). High school
      students reported significantly greater satisfaction than junior high school
      students regarding the interactive video equipment (p = 0.011). White females (p
      = 0.025) and African American males (p = 0.004) in smaller, rural communities
      reported higher satisfaction than White males. The School Telehealth Education
      Program, delivered by interactive compressed video, promoted program satisfaction
      among rural and minority populations and among junior high and high school
      students. Effective program methods included an emphasis on participants'
      learning needs, increasing access in rural areas among ethnic groups, speaker
      communication, and clarity of the program presentation.

PMID- 12212409
TI  - Relationships among adolescent subjective well-being, health behavior, and school
      satisfaction.
AB  - This study examined the relationship among subjective well-being (SWB), school
      satisfaction, and health behavior of Finnish secondary school students (N = 245).
      Pupils (51.0% female) in seventh and ninth grades from 13 secondary schools
      completed an anonymous questionnaire. Adolescent subjective well-being was
      measured using the Berne questionnaire of subjective well-being, and two
      subscales from an original Finnish questionnaire of values and subjective well
      being. Results indicated that school satisfaction, body satisfaction, and self
      rated good health explained 50% of the variance in global satisfaction among
      female respondents. For males, most significant predictors for global
      satisfaction included, in addition to those observed among girls, low-intensity
      drinking which explained 31% of the variance. The most significant associations
      for global ill-being for females were school dissatisfaction, high-intensity
      drinking, and self-rated moderate health, explaining 34% of the variance. In
      global ill-being, the variables of body dissatisfaction and regular drinking
      explained only 14% of the variance for boys. The results support the need to
      enhance adolescent positive attitudes toward life and school, self-perception,
      and adolescent coping with negative emotions.

PMID- 12212410
TI  - Differences in physical activity between black and white girls living in rural
      and urban areas.
AB  - This study examined the relationship of race and rural/urban setting to physical,
      behavioral, psychosocial, and environmental factors associated with physical
      activity. Subjects included 1,668 eighth-grade girls from 31 middle schools: 933
      from urban settings, and 735 from rural settings. Forty-six percent of urban
      girls and 59% of rural girls were Black. One-way and two-way ANOVAs with school
      as a covariate were used to analyze the data. Results indicated that most
      differences were associated with race rather than setting. Black girls were less
      active than White girls, reporting significantly fewer 30-minute blocks of both
      vigorous and moderate-to-vigorous physical activity. Black girls also spent more
      time watching television, and had higher BMIs and greater prevalence of
      overweight than White girls. However, enjoyment of physical education and family
      involvement in physical activity were greater among Black girls than White girls.
      Rural White girls and urban Black girls had more favorable attitudes toward
      physical activity. Access to sports equipment, perceived safety of neighborhood,
      and physical activity self-efficacy were higher in White girls than Black girls.

PMID- 12212411
TI  - Evaluation of a theater production about eating behavior of children.
AB  - This study evaluated "All's Well That Eats Well," a theater production performed
      in 20 schools in the Twin Cities, Minn., metropolitan area in winter 2000. The
      production sought to change food-related knowledge and food choices concerning
      fruits and vegetables among children in grades 1-6. The study used a pretest
      posttest design with two randomly-assigned, sequential intervention-control
      groups (N = 4,093). All students completed surveys prior to and then following
      the theater production and the classroom and home activities. No differences
      existed between the groups at pretest. Significant differences occurred in food
      related knowledge, food choices, and food recall from pretest to posttest for all
      students. Significant differences also occurred between intervention groups in
      food-related knowledge and food choices. The study indicates that professional
      theater productions in schools can create at least a short-term effect on
      children's nutrition knowledge and behavior.

PMID- 12212412
TI  - Implementing a school-based dental health program: the Montefiore model.

PMID- 12212414
TI  - The office of the coroner: past, present and future.

PMID- 12212413
TI  - Patient safety: how are we doing in Australia and England?

PMID- 12212415
TI  - Testicular torsion unravelled.
AB  - Testicular torsion is a true vascular emergency-prompt diagnosis and surgical
      management is critical. If treatment is not instigated within 4-6 hours of the
      onset of pain, irreversible testicular infarction may result, necessitating
      orchidectomy. This review presents the key features, management principles and
      medicolegal considerations of this serious condition.

PMID- 12212417
TI  - Prostate cancer: management and controversies.
AB  - Advances in the management of prostate cancer are associated with uncertainties
      and controversies in screening, who and when to treat, the best treatment option
      for localized disease and what to do with biochemical relapse after presumed
      curative treatment.

PMID- 12212416
TI  - Benign prostatic hyperplasia: solutions to an ageing problem.
AB  - As the population ages, the demand for treatment of the symptoms of benign
      prostatic hyperplasia has never been higher. Equally the choice of treatments has
      never been greater. This review considers the medical and surgical options.

PMID- 12212418
TI  - Using 'citizenship' to deal with feelings of hate in psychiatry.
AB  - Clinicians' feelings of hate towards their patients may contribute to adverse
      clinical outcomes through unintended harm or intended abuse. Ideas of
      'citizenship' may assist psychiatrists and other mental health professionals to
      deal with naturally arising feelings of hate, through engagement in dialogue with
      patients and colleagues, in a spirit of ethical encounter and fellowship.

PMID- 12212419
TI  - Forensic dentistry and human bite marks: issues for doctors.
AB  - The human dentition can be used as a weapon of attack or defence. Bite mark
      injuries are common in cases of sexual assault, child abuse and homicide. Many
      bite injuries are first seen in casualty departments where quick and proper
      recovery of evidence can assist in analysing these injuries. This article
      describes different bite injuries, collection of evidence and comparative
      analysis methods.

PMID- 12212420
TI  - The role of anti-IgE therapies in the treatment of asthma.
AB  - The prevalence of asthma, a chronic inflammatory disease often linked to allergy,
      is on the increase. The introduction of a blocking anti-IgE monoclonal antibody
      (omalizumab) as a new therapy has not only confirmed the pathogenic role of IgE
      in asthma but has also provided a novel therapy for a chronic severe disease
      where there are limited therapeutic options.

PMID- 12212421
TI  - Acute pancreatitis.
AB  - Acute pancreatitis is an important and extremely common cause of acute hospital
      admission which may be associated with major morbidity and mortality. Modern
      treatment is largely supportive with a limited role for surgery.

PMID- 12212422
TI  - Do the Royal college curriculum statements guide the assessment and learning for
      specialist registrars?
AB  - The Royal College curriculum statements should be a vital part of the teaching
      and learning of specialist registrars, and of their assessments. This does not
      appear to be the case in the four specialties studied.

PMID- 12212423
TI  - Treatment of heart failure.

PMID- 12212424
TI  - Giant lipoma of the descending colon.

PMID- 12212426
TI  - Are we going to do a rapid sequence on the next patient, doctor?

PMID- 12212425
TI  - Pyrexia of unknown origin: a swollen gland and a glass of milk.

PMID- 12212427
TI  - Who needs nursing care?

PMID- 12212428
TI  - Room for improvement.

PMID- 12212429
TI  - Self-reported stress and its effects on nurses.
AB  - AIM: The primary aim of this study was to examine the relationship between job
      satisfaction and self-reported stress levels among nurses working in a children's
      hospital in Belfast. The secondary aim was to identify the main causes of stress.
      METHOD: The study was descriptive and analytical. A random sample of 72 nurses
      completed the Nurse Stress Index questionnaire. The data were analysed using the
      Statistical Package for the Social Sciences (SPSS). The respondents' stress
      scores were correlated with job satisfaction scores using bivariate correlation
      and multivariate linear regression. RESULTS: The results of the bivariate
      analysis showed that a negative relationship existed between the subscales of the
      NSI and job satisfaction--as stress levels rise, job satisfaction falls. The
      multivariate analysis revealed that the only significant contribution to job
      satisfaction scores was stress resulting from a perceived lack of organisational
      support and involvement. The top scoring variables from each subscale were ranked
      to reveal the six main causes of stress for the sample. CONCLUSION: Job
      satisfaction is negatively affected by stress. The main sources of stress were
      job context variables, such as shortage of resources, time, management's lack of
      appreciation and initiating change.

PMID- 12212430
TI  - Use of constant comparative analysis in qualitative research.
AB  - This article describes the application of constant comparative analysis, which is
      one method that can be used to analyse qualitative data. The need for data
      analysis to be congruent with the overall research design is highlighted.

PMID- 12212431
TI  - Diabetes-associated cardiovascular risk factors.
AB  - Cardiovascular disease is the biggest killer in the UK and diabetes puts people
      at increased risk of this disease. The role of nurses in reducing cardiovascular
      risk in diabetes is explored.

PMID- 12212432
TI  - A language activity monitor for supporting AAC evidence-based clinical practice.
AB  - Augmentative and alternative communication (AAC) evidence-based practice requires
      the collection and analysis of performance data. This article presents the
      development, evaluation, and application of automated performance monitoring
      tools for use in clinical practice. Language activity monitoring (LAM) is the
      systematic data collection of the actual language activity of an individual who
      relies on AAC. Work completed to date includes the development and evaluation of
      the language activity monitor function, which now is commercially available in
      three forms: (1) a standard feature built into modern high performance AAC
      systems, (2) an external add-on package for use with older AAC devices based on
      synthetic speech, and (3) software that allows the personal computer to serve as
      an LAM in the clinical environment. The LAM records the time and content of
      language events (the generation of one or more letters or words). A logging
      protocol suitable for clinical application has been in use since late 1998. The
      logged data is uploaded periodically to a computer for editing, analysis, and the
      generation of a summary measure report. The applications of this work in the
      areas of clinical service delivery are presented.

PMID- 12212433
TI  - Effects of a wheelchair-mounted rigid pelvic stabilizer on caregiver assistance
      for children with cerebral palsy.
AB  - A within-subjects repeated measures (A1, B, A2) design was used to study the
      impact of a rigid pelvic stabilizer (RPS) compared with a traditional lap belt on
      the caregiver assistance requirements of six children with cerebral palsy as they
      completed functional tasks from their wheelchair seating system. Study
      participants wore a lap belt during the 3-week baseline phases (A1 and A2). The
      RPS was used during the 5-week intervention phase (B). At baseline, each child
      and parent identified five bimanual or reaching tasks with which the child had
      difficulty. Using a six-point scale, each parent (caregiver) rated the degree of
      assistance the child required to do each task. Parents also maintained a log,
      recording how many times the child was repositioned daily. The RPS appeared to
      impact directly on reducing caregiver assistance for 30% of the tasks, as the
      need for assistance was less during phase B when the RPS was used and was greater
      during phases A1 and A2 when the lap belt was worn. Five children required
      repositioning less often during phase B than during the A phases. The RPS reduced
      the child's need for caregiver assistance for some bimanual and reaching tasks as
      well as for repositioning.

PMID- 12212434
TI  - The use of artificial intelligence in the design of an intelligent cognitive
      orthosis for people with dementia.
AB  - Dementia often reduces a person's ability to perform activities of daily living
      because he or she becomes confused and cannot remember the sequence of steps to
      perform. The current solution is to have a caregiver continually supervise and
      assist the person using verbal reminders or cues. This loss of privacy and
      increased dependency may cause the affected person to become embarrassed and
      agitated. We propose that this situation might be improved by using a
      computerized device that monitors progress and provides the reminders needed. The
      COACH is a first prototype of such a device. It uses artificial intelligence to
      observe a user, learn from his or her actions, and issue prerecorded cues of
      varying detail. The device was developed using a personal computer and a video
      camera that unobtrusively tracked the user. Preliminary testing with subjects who
      simulated confused behavior as they washed their hands showed that the device was
      performing its functions with an efficacy of approximately 95%. More extensive
      clinical testing and evaluation has begun, and the results will be reported in
      future publications.

PMID- 12212435
TI  - Efficiency of the Chubon versus the QWERTY keyboard.
AB  - There is little available evidence for claims of the efficiency of alternative
      keyboard layouts. Part of the difficulty in providing such evidence is that
      available research subjects typically have extensive experience with the standard
      keyboard, making a fair comparison of keyboard layouts difficult. The purpose of
      this study was to provide a true comparison of the QWERTY and Chubon keyboard
      layouts for individuals who type with a single digit by neutralizing prior
      experience through an inversion of the QWERTY keyboard. A single-subject,
      repeated measures design was used with a convenience sample of nine participants.
      Each participant began typing on a preselected keyboard and continued typing
      until fluency was achieved. This procedure was replicated with each keyboard
      layout. The words per minute typed at fluency for the Reverse QWERTY was
      approximately 62% of the QWERTY, indicating that the learned effect had been
      erased. The average typing speed of the Chubon was at least 5% higher and at most
      51% higher than the Reverse QWERTY. There were no significant patterns of error.
      Results of this study indicate that the biomechanical layout of the Chubon is
      superior to that of the Reverse QWERTY and, by extension, to that of the QWERTY.
      Additional research is needed to expand knowledge of the effectiveness of the
      various alternative keyboard layouts.

PMID- 12212437
TI  - Assistive technology (AT) Field.

PMID- 12212436
TI  - Product development: using a 3D computer model to optimize the stability of the
      Rocket powered wheelchair.
AB  - A three-dimensional (3D) lumped-parameter model of a powered wheelchair was
      created to aid the development of the Rocket prototype wheelchair and to help
      explore the effect of innovative design features on its stability. The model was
      developed using simulation software, specifically Working Model 3D. The accuracy
      of the model was determined by comparing both its static stability angles and
      dynamic behavior as it passed down a 4.8-cm (1.9") road curb at a heading of 45
      degrees with the performance of the actual wheelchair. The model's predictions of
      the static stability angles in the forward, rearward, and lateral directions were
      within 9.3, 7.1, and 3.8% of the measured values, respectively. The average
      absolute error in the predicted position of the wheelchair as it moved down the
      curb was 2.2 cm/m (0.9" per 3'3") traveled. The accuracy was limited by the
      inability to model soft bodies, the inherent difficulties in modeling a
      statically indeterminate system, and the computing time. Nevertheless, it was
      found to be useful in investigating the effect of eight design alterations on the
      lateral stability of the wheelchair. Stability was quantified by determining the
      static lateral stability angles and the maximum height of a road curb over which
      the wheelchair could successfully drive on a diagonal heading. The model
      predicted that the stability was more dependent on the configuration of the
      suspension system than on the dimensions and weight distribution of the
      wheelchair. Furthermore, for the situations and design alterations studied,
      predicted improvements in static stability were not correlated with improvements
      in dynamic stability.

PMID- 12212438
TI  - On the odyssey: a personal journey.

PMID- 12212439
TI  - Reflections on the use of interviews in the history of science: who will write
      the history of science?
AB  - Interviews are an excellent source of information for historians of science. They
      should be done by historians who understand science in detail and, if possible,
      better than the scientists they interview. In the case of applied industrial or
      governmental sciences, historians must have detailed knowledge of economic or
      historic sources. Again they should know more in these areas than those they
      interview. If, on the contrary, the interviewers are not scientists at heart who
      know science, the history they write will become at best literature but at worst
      pseudoscientific abracadabra.

PMID- 12212440
TI  - What history of evolutionary biology is not.

PMID- 12212441
TI  - Initial theoretical framework and problem solving concerning the enigma of
      heredity.
AB  - The difference in formulation of the question of heredity on a different level of
      knowledge in Brno in the 1830s and after 1850 is discussed in this article. In
      order to solve the problem the most important source is foreshown in the new
      philosophy of plant physiology and in physics. Mendel was pleased to have met
      excellent teachers of both these fields. This explanation is an example of Mirko
      Grmek's thesis: 'l'histoire des sciences est le laboratoire de l'epistomologie'.

PMID- 12212442
TI  - [Mirko D. Gremek: an exemplary journey].

PMID- 12212443
TI  - The discovery of Gramicidin S: the intellectual transformation of G.F. Gause from
      biologist to researcher of antibiotics and on its meaning for the fate of Russian
      genetics.
AB  - The discovery of Gramicidin S is considered to be the outcome of the intellectual
      transformation of Russian biologist G.F. Gause from simply a biologist to a
      researcher of antibiotics. Different historical conditions of this change as well
      as the development of experimental biology itself at this time are analysed in
      detail. The meaning of Gause's occupation of a new 'niche' in soviet science for
      the fate of Russian post-war genetics is defined as well.

PMID- 12212444
TI  - The history of science and the introduction of plant genetics in Mexico.
AB  - The emergence and development of 'national sciences' in Latin American countries
      were not, until very recently, part of the agenda of historians of science
      because the 'traditional' history of sciences was not interested in the
      scientific activity of peripheral areas. The history of science is a recent
      discipline in Mexican historiographic studies. The methodological interest in the
      history of science, the creation of schools and institutes that deal with it, the
      establishment of particular chairs, the organization of national societies, and
      the publication of books and periodicals are all very recent. It is important to
      carry out studies in the history of science that examine the development of
      Mexican science introducing the 'local' context, and study how this development
      has influenced the formation of scientific societies and the development of
      scientific disciplines in the country. We want to explore the introduction of
      genetics in Mexico as applied to agriculture between 1930 and 1960. This matter
      has not been investigated in Mexico and therefore this work would represent one
      of the first studies of this subject and one of the first studies in the general
      field of Mexican scientific history.

PMID- 12212445
TI  - [Necessary sites: identical duplication of living organisms].
AB  - The paper deals with the concept of the identity of living organisms, a concept
      used up until now very ambiguously. The discussion rests on the combination of
      two concepts, one proposed by Munzer (1993) and another derived from the
      considerations of Riedl (1975). The first is the proposal that the identity of
      living organisms depends on the properties of their elementary constituents, such
      as cells and tissues, and that these properties, in turn, depend on those of
      their DNA and RNA. It follows that the identity of a living organism remains
      constant or changes during life according to whether its DNA and RNA content also
      remains constant or changes. The second is the consideration that, during
      duplication of a cell population, the informational content of the population
      does not increase if the duplicated cells are identical (increase only of
      redundant DNA). On the other hand the informational content of the cell
      population increases if the duplicated cells are the result of a variation
      selection process (increase of essential DNA). The changes of DNA and RNA
      content, occurring in the germinal cells during phylogenesis and in the somatic
      cells of the evolutionary systems during ontogenesis, lead, therefore, to the
      generation of new identities. Living organisms are suggested to reflect two types
      of identity, that of the deterministic and that of the evolutionary systems.
      Since the informational content of the deterministic systems (the essential DNA
      content) remains approximately constant during life, their identity also remains
      constant. The changes in the number of elementary constituents and cell volumes
      during the processes of hypertrophy and atrophy are accompanied only by changes
      in the amount of DNA (the redundant DNA). On the other hand the informational
      content of the evolutionary systems (the essential DNA), such as the brain-mind
      system, the immunological system and some receptor systems, undergo a marked
      increase during the ontogenic development: this leads to changes of identity of
      these systems. For example, in the immunological system the process of mutation
      and recombination of the DNA of the immunological cells leads to the generation
      of new proteins in the amount about 10,000 times larger than that produced
      through the decodification of the genome. Also the construction of the neural
      network, and of a number of synapses much larger than that of the neuronal cells,
      requires the generation of an amount of new information much larger than that
      contained in the genome. In short, the attribution of a double identity to living
      organisms reflects the simultaneous presence of systems developing either within
      strictly programmed limits or without programs and limits, say as closed or open
      projects. The difference between the two types of systems explains the different
      effects in the case of the transplants. The identity of the recipient of
      transplants is not altered in the case of transplants of a deterministic system
      but is so in case of transplants of evolutionary systems. There is now a
      widespread fear of the possibility of human cloning. It is argued that this fear
      is unjustified because a cloning process can never succeed in duplicating those
      parts which are essential for the characters of humans, namely those concerned
      with the properties of the evolutionary systems.

PMID- 12212446
TI  - [Mirko D. Grmek and ancient studies].

PMID- 12212448
TI  - [Definition of the real domain of the history of sciences and exploring the
      relationship with the philosophy of science].
AB  - The specific field of the history of science is the study and explanation of the
      origin and transformation of the structures of scientific knowledge. The
      historian of science should render understandable the reality of scientific
      research. The relationships between the history of science and the philosophy of
      science are examined stating that (1) the philosophical theories on the
      development of science have a scientific content only as much as they may be
      compared with the results of the history of science, and (2) the philosophy of
      science does not refer to an immediate historical reality but to an intellectual
      reconstruction of the past.

PMID- 12212447
TI  - [The flux of historiography].
AB  - The author places Grmek's editorial within the flux of the historiographical
      debate which, since the middle of the 1970s, has concentrated on two major crises
      due to the end of social science-oriented 'scientific history' and to the
      'linguistic turn'. He also argues that Grmek's historiographical work of the
      1980s and 1990s was to some extent an alternative to certain observed changes in
      historical fashion and has achieved greater intelligibility because of its
      commitment to a rational vision of science and historiography.

PMID- 12212449
TI  - History of science and the practices of experiment.

PMID- 12212451
TI  - Discovery and disease: history, philosophy, and medicine in the year 2000.

PMID- 12212450
TI  - On the relations between history and philosophy of the life sciences and biology.

PMID- 12212452
TI  - [History and philosophy of sciences: a strategy of convergence].

PMID- 12212453
TI  - [Lasers in dentistry. 5. The use of lasers in periodontology].
AB  - This literature review shows that the Nd:YAG laser and the Er:YAG laser can be
      beneficially used in periodontology for subgingival curettage and gingivectomy.
      Studies demonstrated that subgingival laser treatment can result in significant
      reduction of the initial levels of periodontal pathogens. It is beneficial to
      perform laser curettage under water irrigation prior to scaling in order to
      destroy of the structure of the calculus and its attachment to the root surface.
      During laser curettage sufficient haemostasis is obtained, which improves
      detection of subgingival calculus. Nd:YAG laser gingivectomy results in similar
      improvement of deep periodontal pocket as conventional flap surgery, with the
      advantages such as minimal bleeding and post-operative pain, no swelling, and
      neither sutures nor post-surgical dressing are needed. Both non-surgical and
      surgical laser treatments are often performed without local anaesthesia, making
      full-mouth treatment in one session possible. Treatments are well accepted by the
      patients and require about 50% less time than the conventional therapies. Laser
      de-epithelialization for periodontal regeneration has been experimentally
      attempted, but more controlled studies are needed to establish its usefulness in
      the clinic. Laser treatment of peri-implantitis is not recommended.

PMID- 12212454
TI  - [Oral health care in young people insured by a health insurance fund. 2.
      Prevalence and treatment of malocclusions in the Netherlands between 1987-1999].
AB  - In this paper data are presented about malposition of teeth in 5-, 11-, 17- and
      23-year-olds in the time period between 1987-1999. Furthermore, results are shown
      of a longitudinal study in youngsters 11-17-years of age of whom some were and
      others were not treated orthodontically. Between 1987 and 1999, the percentage of
      youngsters who received orthodontic treatment increased from 23% to 40%. In the
      same time period the percentage of youngsters 17- and 23-year-olds with a
      malposition of teeth decreased. In youngsters involved in the longitudinal study
      and treated orthodontically, a strong improvement of the tooth position was found
      between the age of 11 and 17. Such an improvement did not appear in the non
      treated group. The outcomes are considered as an indication that orthodontic
      treatments have positive effects on individual and on population level.

PMID- 12212455
TI  - [Surgically assisted rapid maxillary expansion: a retrospective study].
AB  - Transverse maxillary hypoplasia, in adolescents and adults, may be corrected by
      means of a 'surgically assisted rapid maxillary expansion' (SARME). The results
      of 7 patients who were treated by means of a SARME, are presented. Attention is
      paid to the technique, the type of expansion, and the stability of the expansion
      of the maxilla 1-1.5 years after SARME. The mean expansion between the cuspids
      was 4.7 mm (sd 1.7) and between the first molars 5.6 mm (sd 3.2). The SARME
      technique appeared to give rise to a predictable result and a sufficient amount
      of expansion, although the sample is small and the follow-up period relatively
      short. All patients had a satisfactory result without complications.

PMID- 12212456
TI  - [Risk factors in adult periodontitis: polymorphism in the interleukin-1 gene
      family].
AB  - Interleukin (IL)-1 alpha, IL-1 beta and IL-1 receptor antagonist (ra) play a
      major role in regulation of the inflammatory response in periodontal tissues. The
      aim of this study was to investigate the distribution of genetic variation in the
      IL-1 gene family among periodontitis patients and controls, taking into account
      smoking and microbiology as additional variables. There were 53 non-smoking and
      52 smoking patients with severe adult periodontitis and 53 periodontal healthy
      controls genotyped for genetic variation in the IL-1 gene family. The presence of
      Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans was established
      by culture techniques. A higher frequency of genotype+ (IL-1A*2 + IL-1B*2 + IL
      1RN*2) was found in non-smoking periodontitis patients in whom P. gingivalis and
      A. actinomycetemcomitans could not be detected (42.1% vs. 11.3% in controls; p =
      0.0068; or 5.7, 95% ci: 1.6-19.8). This data provide evidence that polymorphisms
      in genes of the IL-1 family are associated with severe adult periodontitis and
      may be a risk factor for severe periodontitis.

PMID- 12212457
TI  - [Water-quality of Westbrabantse dental units and the effect of flushing].
AB  - Dutch literature is not very clear about whether or not the effluent water/spray
      of handpieces of dental units meets the Dutch standards of potable water (< 200
      CFU/ml and no pathogens). To improve the quality of dental unit water, flushing
      or purging the waterlines is recommended. In this study the quality of the
      effluent water/spray of 9 dental units was measured at the beginning of the day
      before and after 2 minutes flushing (sample size 25 ml) and the end of the day
      before and after 20 seconds flushing (sample size 5 ml). All units easily met the
      potable water standards after 2 minutes flushing, but after 20 seconds the effect
      was less impressive. The overall larger number of bacteria found after 20 seconds
      flushing can be explained as a matter of chance, whether or not a by turbulence
      loosened part of the biofilm has entered the small sample taken.

PMID- 12212458
TI  - [A sixth sense: bone as mechanosensor].

PMID- 12212459
TI  - [NVT-Spring Congress: "The crown of the job"].

PMID- 12212460
TI  - [Sticky saliva: a real complaint?].

PMID- 12212461
TI  - [Imported diseases 1].

PMID- 12212462
TI  - [Packages of care in the departments of mental health in Lombardy].
AB  - OBJECTIVE: The analysis aims to study the packages of care in the public
      Departments of Mental Health by diagnosis and service utilisation intensity.
      DESIGN: Data on community, hospital and residential contacts were provided by the
      Regional Psychiatric Information System. The sample has been composed by 55,518
      patients residents in Lombardy and treated in public Departments of Mental
      Health. SETTING: The public Departments of Mental Health in Lombardy. MAIN
      OUTCOME MEASURES: Fifteen packages of care were defined according to researchers'
      experience; the package "community care only" has been divided in five sub
      packages; for every package the care weight has been attached. RESULTS: Four
      packages of care ("community care only", "hospital care plus community care",
      "hospital care only" "community care plus day centre care") represented 95% of
      the patients. Three quarter of the patients were treated only in the community
      setting, without hospital, residential and day centre contacts in the year.
      Heavier patients (patients with more than 5000 care weight) represent only 4%.
      Residential care is the heavier setting (36% of the total weight), while
      schizophrenia is the diagnosis with mayor impact on the community services (59%
      of the total weight). Of the patients treated only in the community setting one
      third receives only psychological and psychiatric visits, while two thirds
      integrated community care. Conclusions in community care the mixed packages
      represent the exception not the rule. More complex or heavier packages are
      addressed to severe mental illness patients.

PMID- 12212464
TI  - [Effectiveness of cognitive-behavioral treatment in social phobia: a description
      of the results obtained in a public mental health service].
AB  - OBJECTIVE: Cognitive Behavioural Therapy for the treatment of Social Phobia has
      proved effective through several controlled trials and meta-analyses. In spite of
      this the CBT has not spread in clinical field yet. Therefore our aim was to
      verify the effectiveness of the CBT in a public mental health service and to
      compare our results with those described by experimental research. DESIGN AND
      SETTING: Participants were 11 public mental health center clients, with a primary
      diagnosis of Social Phobia (according to DSM-IV criteria). The transportability
      of CBT to a common clinical setting was examined comparing treatment outcome
      data, at the end of the treatment and at a six months follow up, with results
      described in controlled efficacy studies. We employed self completion rating
      scales relating to both general health conditions and life satisfaction (SF36)
      and trend of symptoms (LSPS). Moreover we recorded the Clinical Global Impression
      (CGI) and Patient's Global Impression (PGI). RESULTS: Despite differences in
      setting, clients and treatment providers, both the magnitude of change from pre
      treatment and maintenance of change at a six months follow up were comparable
      with the parallel findings in the efficacy studies. CONCLUSIONS: The results
      attest the effectiveness of CBT even in a public mental health center setting so,
      in consideration of the fact that social phobia is a very common disease and
      involve high degree of severity, chronicity and disability, we hope that this
      effectual and relatively cheap therapy will be routinely applied in public mental
      health services.

PMID- 12212463
TI  - [Phenomenology of patients with early and adult onset obsessive-compulsive
      disorder].
AB  - OBJECTIVE: To evaluate potential differences in socio-demographic and clinical
      characteristics (obsessive-compulsive symptomatology, axis I and II comorbidity)
      between OCD adults with an early age at onset (< 18 years) and later onset, (> or
      = 18 yrs). DESIGN: Clinical controlled study. SETTING: Anxiety and Mood Disorders
      Unit, Department of Neuroscience, University of Turin. METHODS: We included 149
      subjects with a principal diagnosis of OCD (DSM-IV) and a Y-BOCS total score > or
      = 16. All patients underwent a semistructured clinical interview aimed at
      investigating sociodemographic characteristics and clinical features of the
      disorder. Lifetime Axis I comorbidity, according to DSM-IV criteria, was
      investigated with a structured interview following Othmer & Othmer guidelines
      (1994; 1999). Personality disorders were assessed using the Structured Clinical
      Interview for DSM-IV Axis II Disorders (SCID-II). RESULTS: 39 patients referred
      age at onset of OCD before 18 years (early-onset group) and 110 patients at 18
      years or later (later-onset group). Significant differences were found between
      the two groups: early-onset subjects are characterized by a preponderance of
      males, a chronic course of illness and a strong association with Schizotypal
      Personality Disorder. DISCUSSION: When subtyping OCD according to age at onset we
      found significant differences which suggest a possible heterogeneity of the
      disorder. Our results seem to confirm that early-onset OCD may represent a more
      severe subgroup, with clinical characteristics such as the chronic course and the
      high association with Schizotypal PD which are significant in order to apply
      specific therapeutic strategies.

PMID- 12212465
TI  - [Which psychotherapy in the departments of mental health? From evaluation issues
      a few ideas to discuss].
AB  - AIMS: Taking the scientific literature on psychotherapy as a starting point, the
      paper suggests a few remarks for the debate over psychological treatments in the
      mental health services in Italy. METHODS: A survey of reviews and papers on
      process and outcome of psychological treatments and on psychotherapeutic practice
      in mental health services. RESULTS: The paper examines some organizing hypotheses
      in order to increase psychological treatments supplies. CONCLUSION: The
      practicability of such solutions requires on the one hand more attention for
      empirically supported psychological treatments in mental health professionals
      training and, on the other hand, that various health services become able to be
      different in their treatments supply.

PMID- 12212466
TI  - Depression and mortality following myocardial infarction: the issue of disease
      severity.

PMID- 12212467
TI  - The connection of depression and heart disease and its implications.

PMID- 12212468
TI  - [Depression, anxiety and cardiovascular disease: biological correlations and
      therapeutic strategies].

PMID- 12212469
TI  - The WHO World Health Report 2001 on mental health.
AB  - OBJECTIVE: 450 million people are estimated to suffer from neuropsychiatric
      conditions; approximately 10-20% of all children seem to have one or more mental
      or behavioural problems. Mental and neurological conditions account for 31% of
      all disability in the world. In epilepsy alone less than 25% of those affected
      receive treatment. In developing countries only a quarter of people suffering
      from schizophrenia receive treatment. Urgent action is needed to close the
      treatment gap and to overcome barriers. Governments need to take action with
      other partners to address these barriers and provide mental health services to
      those in need. RESULTS: The World Health Report provides 10 recommendations for
      countries to begin taking action. These actions are divided into three scenarios:
      for countries with a very low level of mental health resources, for those with a
      medium level and for those with a high level of resources. CONCLUSIONS: The
      Report allows every nation to recognize itself in one of three scenarios and to
      adopt and implement the appropriate actions.

PMID- 12212470
TI  - Anatomical MRI findings in mood and anxiety disorders.
AB  - OBJECTIVE: In vivo structural magnetic resonance imaging (MRI) studies have
      evaluated the brain anatomy of various psychiatric disorders, allowing the
      investigation of putative abnormal brain circuits possibly involved in the
      patophysiology of psychiatric disorders. Here we reviewed the structural MRI
      literature in mood and anxiety disorders. METHODS: All anatomical MRI studies
      evaluating mood and anxiety disorder patients were identified through a
      comprehensive Medline search conducted for the period from 1966 to January 2002,
      and a manual search of bibliographic cross-referencing complemented the Medline
      search. RESULTS: Differential patterns of anatomical brain abnormalities appear
      to be involved in subtypes of mood disorders, with hippocampus and basal ganglia
      being abnormal in unipolar disorder, and amygdala and cerebellum in bipolar
      disorders, suggesting that these two mood disorders are biologically distinct. As
      for anxiety disorders, orbital frontal regions and basal ganglia have been
      reported to be anatomically abnormal in obsessive-compulsive disorder, temporal
      lobe was found to be abnormally reduced in panic disorder, and abnormal
      hippocampus shrinkage was shown in posttraumatic stress disorder. CONCLUSIONS:
      The structural MRI findings reviewed here suggest abnormalities in specific brain
      regions participating in proposed neuroanatomic models possibly involved in the
      pathophysiology of mood disorders and anxiety disorders. Nonetheless, available
      MRI studies have suffered from limitations related to relatively small patient
      samples and involvement of medicated patients, and were largely cross-sectional
      investigations. Therefore, longitudinal MRI studies involving more sizeable
      samples of drug-free patients, patients at first episode of illness or at high
      risk for mood or anxiety disorders, associated to genetic studies, are likely to
      be extremely valuable to separate state from trait brain abnormalities and to
      characterize further the pathophysiology of these disorders.

PMID- 12212471
TI  - [Particles and mortality].

PMID- 12212473
TI  - [Juvenile idiopathic arthritis].
AB  - The new classification of juvenile idiopathic arthritis (JIA) is described in
      this review. Clinical characteristics divide JIA in to subtypes: systemic,
      oligoarticular (persistent and extended type), RF-positive and--negative
      polyarticular, enthesitis-related arthritis and psoriatic arthritis. In addition
      to the clinical characteristics, genetic and biochemical differences suggest that
      JIA could be regarded as a general term covering various diseases. Complications
      described are uveitis, temporomandibular joint affection and growth disturbances.
      The therapeutic strategy should be planned individually according to age, subtype
      and disease activity and carried out as teamwork with several specialties. Drugs
      showing significant effectiveness in controlled studies are primarily
      methotrexate and sulphasalazine. An immunomodulating agent, etanercept, a soluble
      TNF alpha-receptor fusion protein, has shown a promising effect in severe
      polyarticular JIA refractory to methotrexate treatment.

PMID- 12212472
TI  - [Effects of traffic-generated ultrafine particles on health].
AB  - Epidemiological studies have consistently shown relation between exposure to
      particulate matter in urban air and cardiovascular and pulmonary morbidity and
      mortality. Some recent population studies suggest that the ultrafine fraction of
      particulate matter generated by motorised vehicles is particularly damaging.
      Animal studies and cell culture experiments support this hypothesis and address
      the possible mechanisms of action. Inhalation of particulate matter, especially
      ultrafine particles, causes oxidative stress and inflammation in lung tissue,
      which affects the lung cells per se, as well as the cardiovascular system.

PMID- 12212474
TI  - [Pregnancy-related thrombocytosis].
AB  - Pregnancy-related thrombocythaemia comprises myeloproliferative and inflammatory
      reactive subsets. In pregnant women treated for myeloproliferative disorders,
      especially polycythaemia vera and primary thrombocytosis, only 50-70 per cent are
      delivered successfully of a normal healthy baby. The maternal complications are
      cerebral, cardiac, and abdominal arterial thrombosis, and with deep venous
      thrombosis of the legs, whereas bleedings are mainly seen in the case of extreme
      thrombocythaemia, owing to absorption of factors by the platelets. The foetal
      complication are dominated by abruptio placentae, pre-eclampsia, placental
      insufficiency, and death. Reactive thrombocythaemia includes the physiological
      rise in platelets postpartum, believed to be part of the normal maternal
      haemostasis, which almost never causes thromboembolic complications, as far as is
      known today. In contrast, the inflammatory reactive thrombocythaemia, related to
      severe foetal and/or maternal necrosis, is generally related only to a moderate
      rise in the platelet count. As the blood-platelet count does not appear to be
      routine at general pregnancy check-ups, it is necessary to be aware of risk
      groups, consisting of women with otherwise unexplained abortions or stillbirths,
      unexplained foetal and placental malformations, and pre-eclampsia, even if the
      woman has never had any thromboembolic complications.

PMID- 12212475
TI  - [Transport-in vitro-fertilization/intracytoplasmic sperm injections in Denmark].
AB  - INTRODUCTION: This study describes the results obtained with a small IVF/ICSI
      transport programme carried out between a private specialist clinic and a public
      IVF-clinic. MATERIALS AND METHODS: All women treated in the specialist clinic
      over a three and a half years period were entered. Ovarian stimulation, oocyte
      aspiration, and the follow-up after fertilisation were carried out in the
      specialist clinic, whereas fertilisation, culture and embryo transfer were
      performed in the public IVF clinic 25 km away. The oocytes were transported in an
      insulated box kept at 37 degrees C. RESULTS: Totally 314 stimulation cycles were
      performed with 68% IVF, 19% ICSI, and 13% cycles with cryopreserved oocytes
      (FER). The material comprises 259 oocyte aspirations with a total of 1969
      oocytes, 1229 were fertilised. Oocyte and transfer-data are given in Table 2. The
      pregnancy rate was 29% for IVF and 27.1% for ICSI, but only 12.2% in FER.
      DISCUSSION: These results are consistent with that of other private and public
      IVF treatments in Denmark, where differences in population and oocyte handling
      are comparable (Table 3). As reported from the Netherlands, the UK, and Argentina
      (Table 4) transportation of oocytes does not seem to damage their potential for
      fertilisation and implantation.

PMID- 12212476
TI  - [Health life years lost due to smoking].
AB  - BACKGROUND: The aim of the study was to estimate health expectancy--that is, the
      average lifetime in good health--in never smokers, ex-smokers, and smokers in
      Denmark. MATERIAL AND METHODS: A method suggested by Peto and colleagues in 1992
      for estimating smoking-attributable mortality rates was used to construct a life
      table for never smokers. This table and the relative risks of death for ex
      smokers and smokers versus never smokers were used to estimate life tables for ex
      smokers and smokers. Life tables and prevalence rates of health status were
      combined and health expectancy was calculated by Sullivan's method. RESULTS: The
      expected lifetime of a 20 year-old man who will never begin to smoke is 56.7
      years, 48.7 of which are expected to be in self-rated good health. The
      corresponding figures for a man who smokes heavily are 49.5 years, 36.5 of which
      are in self-rated good health. A 20 year-old woman who will never begin to smoke
      can expect to live a further 60.9 years, with 46.4 years in self-rated good
      health; if she is a life-long heavy smoker, her expected lifetime is reduced to
      53.8 years, 33.8 of which are in self-rated good health. Health expectancy based
      on long-standing illness is reduced for smokers when compared with never smokers.
      DISCUSSION: Smoking reduces the expected lifetime in good health and increases
      the expected lifetime in poor health.

PMID- 12212477
TI  - [Effects on health of particulate air pollution in Denmark--a quantitative
      assessment].
AB  - INTRODUCTION: Ambient air pollution is a risk factor for mortality and morbidity.
      The aim of this study was to quantify the health effects related to particulate
      matter (PM10) in Denmark. MATERIALS AND METHODS: We used relative risk estimates
      in relation to PM10 based on the epidemiological literature. Population exposure
      to PM10 was calculated. Cases attributable to PM10 were estimated for mortality,
      cardiovascular and respiratory hospital admissions, chronic bronchitis, acute
      bronchitis, restricted activity days, and asthma attacks. Moreover, we attempted
      to estimate health-related gains from equipping all heavy-duty vehicles in
      Denmark with particle filters. RESULTS: We estimated the average population PM10
      exposure to be about 22 micrograms/m3, about one third of which can be attributed
      to natural (not man-made) PM10. The number of cases per year attributable to the
      estimated exposure included about 5,000 deaths, about 5,000 hospital admissions,
      about 5,000 cases of chronic bronchitis, about 17,000 cases of acute bronchitis,
      about 200,000 asthma attacks, and about three million restricted activity days.
      The health-related gains from installing particle filters on all heavy-duty
      vehicles in Denmark are uncertain; the estimates for mortality ranged from 22 to
      1,250, depending on the assumptions. DISCUSSION: Although air pollution
      constitutes only a minor risk factor on the individual level, it seems to be a
      major public health problem. The particle characteristics responsible for the
      estimated health effects are not well understood. The ultrafine particle fraction
      may cause a much greater impact on health than indicated by the mass.

PMID- 12212478
TI  - [HIV in Western Denmark. Demographic data from a population-based cohort study].
AB  - INTRODUCTION: The course of HIV infection has changed since the introduction of
      highly active anti-retroviral treatment. MATERIAL AND METHODS: We present
      demographic data from an observational database on HIV and AIDS in the Western
      part of Denmark, a region representing 2,935,156 individuals, or 55.1% of the
      population in Denmark (1 January 2000). Five centres in the region treat HIV
      positive adults; all patients attached to these centres since 1995 are included.
      Altogether 749 adult HIV-infected individuals were enrolled as of 31 December
      1999. Estimates of the prevalence and incidence of HIV infection in the area were
      25.8/100,000 and 2.6/100,000 respectively, which are lower than the average for
      the country. RESULTS: The number of newly diagnosed HIV-infected patients
      remained constant in the period 1995-1999 with an average of 62 diagnoses per
      year. The number of HIV-related deaths declined from 43 in 1995 to 15 in 1999.
      DISCUSSION: There seems to be a shift in the HIV epidemic over the last few
      years, with a higher proportion of newly diagnosed HIV-patients who have
      contracted the infection through heterosexual contact, and a higher proportion
      who are immigrants from less developed countries.

PMID- 12212479
TI  - [Forty four pregnancies with idiopathic thrombocytopenic purpura].
AB  - INTRODUCTION: The aim of this project was to describe the course of pregnancy
      with idiopathic thrombocytopenic purpura (ITP) and to estimate risk factors and
      indications for treatment. MATERIAL AND METHODS: Birth, haematological, and
      neonatal files were examined retrospectively. RESULTS: Forty-eight ITP women with
      55 pregnancies gave birth to 61 children, 59 live-born. The first singleton
      pregnancy in the observation period (the index pregnancy) was used for
      statistics, namely 44 index pregnancies. A maternal platelet fall from the first
      trimester to delivery was seen, as was a platelet rise three days after delivery
      (p < 0.0001), even in splenectomised women. Thirty-six per cent of the women had
      bleeding manifestations, none of which were fatal; 33% of the newborn infants had
      thrombocytopenia in cord blood. The following risk factors for perinatal
      thrombocytopenia were found: a sibling with thrombocytopenia, severe maternal
      thrombocytopenia, male gender. The nadir platelet count in the newborn infants
      was seen up to seven days after delivery. The presence of an older sibling with
      neonatal ITP is a risk factor for neonatal ITP in subsequent pregnancies. A
      significant association was found between the maternal platelet count in the
      second trimester and the platelet count in cord blood. DISCUSSION: The diagnosis
      and treatment of ITP in pregnancy are controversial. Vaginal delivery is
      generally recommended. The platelet kinetics in pregnancy with ITP is comparable
      with the platelet kinetics of the spleen.

PMID- 12212480
TI  - [Treatment of apoplexy in Europe].

PMID- 12212481
TI  - [Hormone replacement therapy in menopause and cardiovascular disease].

PMID- 12212482
TI  - [Postmenopausal hormone replacement therapy--is there a cause of worry?].

PMID- 12212483
TI  - [The unfortunate NNT].

PMID- 12212484
TI  - [Ambulatory myelography].

PMID- 12212485
TI  - [Budd-Chiari syndrome after herbal tea?].

PMID- 12212486
TI  - [Nutrition and tumoral growth].
AB  - Some nutrients, such as glutamine, arginine, omega-3 fatty acids and nucleotides
      have been shown to modulate the immune and intestinal systems. They affect the
      synthesis of proteins and the expression of enzymes, as well as the activation
      and the proliferation of leukocytes and enterocytes. Since these immunonutrients
      modulate the response of tissues with rapid cell turnover, such as spleen,
      thymus, bone marrow and intestinal mucosa, they may also affect, such as
      suggested by some preliminary results, cancer cell proliferation and tumour
      growth. Therefore, further investigations are needed to understand the underlying
      mechanisms and to determine possible advantages and limitations of their
      administration to cancer patients.

PMID- 12212487
TI  - [Modulation of immunity in cancerous patient : an weapon with double edges?].
AB  - Nutritional support of cancer patients should ideally contribute to improve the
      immune defence, maintain the protein body pool and sensitize the tumour to
      oncologic treatments. Such a goal is not easy to achieve, because any nutritional
      support efficient at stimulating immune response and protein syntheses might also
      simultaneously stimulate the tumour growth. Contradictory observations have been
      reported for several nutrients contained in the nutritive solutions available on
      the market. This is the case for glutamine, arginine, omega-3 fatty acids and
      nucleotides. Their clinical use during oncologic therapies deserves further
      testing and analysis.

PMID- 12212488
TI  - [ Evaluation of the nutritional state of patients in emergency services:
      contribution in measurement of body composition].
AB  - Weight and body mass index are used in clinical routine to detect malnourished
      patients. However, a study performed at the emergency admission of the University
      Hospital of Geneva shows that the prevalence of malnutrition is very
      underestimated when based on body mass index instead of fat-free mass. Indeed, a
      third of the patients with normal body mass index, i.e. between 20 and 24.9
      kg/m2, present a fat-free mass under percentile 10. This suggests that the body
      mass index alone cannot be used as diagnostic criteria for malnutrition. This
      review describes the prevalence of malnutrition at the emergency admission of the
      University Hospital of Geneva, the prevalence of malnutrition in the literature
      and its relationship with length of hospital stay and mortality.

PMID- 12212489
TI  - [Parenteral nutrition in the Swiss hospitals: a three years national survey].
AB  - Total parenteral nutrition (TPN) requires the perfusion of more than 40 compounds
      (glucose, amino acids, lipids, electrolytes, vitamins and trace elements). Many
      systems of application are used. With the help of pharmacists, the current types
      of products and methods of TPN administration, as well as the evolution of TPN
      practice were evaluated in the Swiss hospitals during three consecutive years.
      Six different TPN systems are commonly used for adult patients. All lead to the
      administration of TPN in "all-in-one" admixtures. For adults, formula compounding
      is provided in large hospitals only. For pediatric TPN, formula compounding is
      routinely performed in the hospitals because individualized compositions are not
      available commercially. Regarding TPN-admixtures outpatients, they are mostly
      compounded in hospital pharmacies and delivered by 3 large hospitals.
      Compositions of TPN formula comply, on average, with European guidelines. An
      increased number of multidisciplinary nutritional support teams is still
      necessary to optimize the medical and economical management of TPN.

PMID- 12212490
TI  - [Microgravity and weightlessness: experimental model accelerates nutritional
      pathology].
AB  - Short space flights affect nutritional intakes, body composition and functional
      parameters. Prolonged space flights (SF) over weeks or months further worsen
      these alterations and result in acute or chronic physical deterioration at earth
      return. Current planning of SF to Mars, with microgravity conditions for more
      than 2 years, stresses the need for developing and optimising a nutritional
      program and physical countermeasures to prevent body mass atrophy and functional
      body alterations. This review presents the models of microgravity simulation on
      earth and the main effects of weightlessness on body composition, protein
      metabolism, hormonal profile and muscle function. It summarizes contradictory
      findings related to the oxidative stress related to SF. It discusses potential
      countermeasures (nutrition, physical activity) to the negative effects of
      microgravity on human body. Future research possibilities in ground and space
      medicine are evoked.

PMID- 12212491
TI  - [Professional satisfaction of American physicians in the Managed Care context].
AB  - The objective of this article is to shed a light on the satisfaction of
      physicians (both primary care physicians and specialists) in the Managed Care
      context. Most surveys have brought in negative results. The article also analyzes
      the resources and the means used by physicians to express their discontent in
      this new era.

PMID- 12212492
TI  - [Monosegmental , degenerative, cervical discopathy treated by surgery with
      insertion of an intervertebral cage].
AB  - Monosegmental, degenerative, cervical discopathy may become symptomatic because
      of spinal instability or neurocompression and may present as cervicalgia,
      radiculopathy and myelopathy. Conservative therapy of these conditions is
      indicated only in case of minor symptoms. In patients with radiculopathy, this
      treatment may be used for a longer period of time than in individuals with
      myelopathy. However, the disorder may progress and lead to irreversible
      complaints, especially in case of myelopathy. Therefore, the surgical treatment
      is preferred: if conservative therapy does not improve symptoms within a short
      period of time and if the patient continues to suffer, surgery is clearly
      indicated. Only recently, novel surgical methods such as microtechniques and cage
      surgery were introduced. The results of these types of surgery in this
      indications are very favourable with respect to recovery from pain, paresis and
      sensory deficits, rates of fusion of the motion segment, morbidity and mortality.

PMID- 12212493
TI  - [Changes in life rhythm when children start school].

PMID- 12212494
TI  - [Continuing education: an occasion to create].

PMID- 12212495
TI  - [The plague, again. Usefulness of basic research].

PMID- 12212496
TI  - [Hyponatremia caused by thiazide diuretics: be aware of drug combinations which
      enhance this effect].
AB  - In 3 patients, two women aged 88 and 82 and a man aged 76, the consciousness
      became disrupted due to a severe hyponatraemia, after a thiazide diuretic had
      been combined with another drug without laboratory control. After a change in
      medication, the laboratory values and the patients' conditions normalised. Severe
      hyponatraemia is a well known but rare complication of thiazide therapy. It has a
      significant mortality and morbidity rate. The risk is greater for elderly women.
      This effect on serum sodium can be enhanced by the use of other drugs like
      furosemide, carbamazepine, paroxetine and NSAIDs. That a patient uses a thiazide
      is sometimes overlooked when a combined preparation of other drugs is prescribed.
      Diuretic serum electrolytes should be monitored once treatment with thiazide has
      been started, especially in elderly patients taking other drugs.

PMID- 12212497
TI  - [Control of drug-sensitive and (multi-)resistant tuberculosis].
AB  - Tuberculosis is an important cause of death in the world. It can be controlled by
      applying the WHO 'directly observed therapy, short-course' (DOTS) strategy. This
      strategy aims at detecting at least 70% of new, smear-positive tuberculosis cases
      and curing at least 85% of these. At present, only 27% of tuberculosis cases are
      treated according to this strategy. Application of the WHO DOTS strategy can
      prevent multidrug-resistant (MDR) tuberculosis. However, where MDR tuberculosis
      has become a large problem, as it has in some Eastern European countries,
      additional measures may be required for its control. Important problems remain
      with respect to the feasibility and costs of these measures and the prevention of
      additional resistance.

PMID- 12212498
TI  - [Systematic reviews in practice. IX. Determining their place in treatment
      recommendations in practice guidelines].
AB  - In a systematic review (SR), the available evidence for a clinical problem is
      systematically and comprehensively collected from different studies, the
      likelihood of bias is assessed and the results are summarised in a reproducible
      manner. The results of an SR can be used in either individual patient care or the
      formulation of a practice guideline. Throughout the world, (national)
      organisations for guideline development use systems for classifying the validity
      of evidence according to the study design ('levels of evidence'), and this is
      also the case in the Netherlands. In formulating a treatment recommendation,
      consideration must be given to the various factors which determine the strength
      of the evidence: study design, consistency of the results (if more studies are
      available), quality of the individual studies, magnitude and precision of the
      reported effect and the clinical relevance of the outcome measures. If
      insufficient studies with the same outcome measure are available, problems can
      arise in an SR. In practice, problems can also arise with respect to estimating
      the cogency of an SR compared to another review or primary studies. For the same
      subject, there might be discordant reviews, differences between reviews and
      megatrials might exist or just one randomised clinical trial might be available.
      These problems can often be solved with the aid of a systematic analysis. This
      requires both methodological and clinical expertise.

PMID- 12212499
TI  - [Clinical reasoning and decision making in practice. Fever, purpura and
      hemiparesis in a 29-year old female].
AB  - A 29-year-old female was admitted with fever, purpura and hemiparesis. She was
      treated for meningococcal sepsis after a Gram stain of a purpuric lesion showed
      Gram-negative diplococci. CT scan of the brain revealed multiple haemorrhagic
      lesions with obliteration of the sulci and basal cisterns. In the course of the
      disease she developed an acute myocardial infarction. Besides wall motion
      abnormalities, echocardiography revealed a bicuspid aortic valve with a
      vegetation on one of its cusps. Despite these findings, both the doctors who were
      involved in the treatment of this patient and the consulted physician in this
      article failed to reject the diagnosis 'meningococcal sepsis' and to replace it
      with a more likely diagnosis, namely Staphylococcus aureus endocarditis. The
      patient died one day after admission due to transtentorial herniation. Although
      purpuric lesions are common in meningococcal sepsis, they are not specific for
      this disease. The false-positive result of the Gram stain resulted in a process
      known as 'premature closure': the diagnosis of meningococcal sepsis was accepted
      before it was fully verified. In this case, the consequence was that other
      diagnostic tests and symptoms were misinterpreted with the result that
      inappropriate antibiotic therapy was instituted.

PMID- 12212500
TI  - [Diagnostic image (101). A woman with painful joints. Dysplasia epiphysealis
      multiplex].
AB  - A 55-year-old woman had progressive tenderness of joints due to dysplasia
      epiphysealis multiplex. Her 16-year-old son appeared to have the same disorder.

PMID- 12212501
TI  - [Radionuclide-guided minimally invasive rib biopsy for metastases].
AB  - OBJECTIVE: To determine the feasibility of radionuclide-guided surgical rib
      biopsy in patients in whom a local metastasis is suspected. DESIGN: Descriptive.
      METHOD: In eight patients (three men and five women) with a known primary
      carcinoma, radionuclide-guided surgical rib biopsy was performed because a local
      metastasis was suspected. The skin was marked on the basis of a technetium-99m
      (99mTc)-medronate scintigram. During surgery, a gamma probe was used to look for
      the hot spot in the rib in the vicinity of the skin marking; this hot spot was
      then minimally excised and submitted for pathological examination. RESULTS: In
      all patients, the radionuclide-guided rib biopsy resulted in an unequivocal
      histopathologic diagnosis: tumour metastasis (n = 2), necrosis (n = 1), old
      fracture (n = 5). CONCLUSION: Radionuclide-guided surgical bone biopsy has been
      shown to be a specific, simple, minimally invasive technique for obtaining a
      representative histological specimen with little stress on the patient. This
      technique can be used in every hospital that is equipped to carry out the
      sentinal node procedure in case of breast cancer or melanoma.

PMID- 12212502
TI  - [Favorable current prognosis after HLA-identical bone marrow transplantation for
      children with required severe aplastic anemia; evaluation of 30 years of bone
      marrow transplantation at the Leiden University Medical Center].
AB  - OBJECTIVE: To evaluate the results of 30 years of allogeneic HLA-identical bone
      marrow transplantation (BMT) as the treatment for children with acquired severe
      aplastic anaemia. DESIGN: Retrospective, descriptive. METHOD: Of all patients who
      underwent an HLA-identical sibling-donor BMT for severe aplastic anaemia at the
      Department of Paediatrics, Leiden University Medical Center, in the period 1971
      2000, and had a follow-up period of at least 1 year, the medical data were
      reviewed. The patients were split into 2 groups: patients transplanted before
      1989 (n = 24), and patients who had their BMT from 1989 onwards (n = 20). This
      was due to a change in the treatment policy, namely a reduction in the period
      between diagnosis and BMT, resulting in fewer blood transfusions as well as
      changes in the prophylaxis against graft-versus-host disease (GvHD) from 1989
      onwards (combination therapy using methotrexate and cyclosporin). RESULTS: There
      was an increase in the 1-year actuarial survival rate from 67% in the period
      before 1989 to 90% thereafter. The incidence of GvHD has significantly decreased
      since the introduction, in 1989, of the combination therapy using methotrexate
      and cyclosporin, with only 1/20 patients suffering from acute GvHD versus 13/24
      prior to 1989 (p = 0.002). No patients acquired chronic GvHD after 1989, whereas
      before 1989, 10 patients had acquired this (p = 0.001). CONCLUSION: The prognosis
      of allogeneic HLA-identical sibling transplantation for paediatric patients with
      severe aplastic anaemia has considerably improved over the last 30 years due to
      improved supportive care, a significant decrease in GvHD and a shorter period
      between diagnosis and BMT, with the result that less blood transfusions have been
      required and less sensitisation has occurred. The long-term survival chance has
      increased to 90%.

PMID- 12212503
TI  - [Osteomyelitis in children: sometimes hard to recognize].
AB  - In a 15-year-old girl with pain in the right lower abdomen and a 9-year-old boy
      with pain in the left thigh, an elevated sedimentation rate and C-reactive
      protein were reason to suspect osteomyelitis. Although no abnormalities could be
      seen on X-rays, skeletal scintigraphy revealed pathology in Liv-v and the
      sacroiliac joint, respectively. In the girl, Staphylococcus aureus was cultivated
      from material obtained by puncture and biopsy. After treatment with antibiotics,
      rest and gradual mobilisation, the girl retained a scoliosis; the boy was cured
      without residual complaints or abnormalities. Osteomyelitis of the spine and
      sacroiliac joint are rare disorders in children. The subtle and non-specific
      symptoms sometimes make the diagnosis difficult. Conventional X-ray is the
      primary radiological investigation. Bone scintigraphy (99mTc-oxidronate) is
      useful in the initial evaluation of children with suspected osteomyelitis. It is
      sensitive, relatively inexpensive, often does not require sedation and can detect
      multiple foci of disease. MRI is also highly sensitive and more specific than
      bone scintigraphy, but it cannot be used as a screening technique when the site
      of pathology is unclear. MRI is useful when the bone scintigram is inconclusive
      and in complicated cases for better anatomic details.

PMID- 12212504
TI  - [One hundred years of the Association of Surgeons in the Netherlands. IX.
      Pediatric surgery].
AB  - The Working Group 'Surgrey in Children and Newborns', founded in 1974, was the
      precursor of the first subsection of the Association of Surgeons in the
      Netherlands, founded in 1981: the Netherlands Association for Paediatric Surgrey.
      Around 1900, paediatric surgery acquired an identity on the basis of what took
      place in children's hospitals. All the admissions were then on social indications
      with a surgeon being called in as a consultant if necessary. Following the Second
      World War, the development in anaesthesia and analgesia and an increasing
      understanding of metabolic processes made ever larger operations possible. The
      required specific expertise and the need to bring it together were decisive
      arguments for the foundation of the subsection. Since then, the developmental
      biological and genetic aspects of severe congenital malformations have, inter
      alia, become new topics for investigation; the consequences for medical ethics
      continue to be a point for attention.

PMID- 12212506
TI  - [Perinaud syndrome as sign of acute obstructive hydrocephalus: recovery after
      acute ventriculostomy].

PMID- 12212505
TI  - [Universal vaccination against group C meningococci and pneumococci; advice from
      the Health Council of the Netherlands].

PMID- 12212507
TI  - [Breast cancer screening discussion].

PMID- 12212508
TI  - [Antibiotics, plea for a cultural revolution].

PMID- 12212509
TI  - [Prostate cancer, generalized screening soon?].

PMID- 12212510
TI  - [Society, medicine and caregiver stress].
AB  - CARING STAFF DISTRESS: Is a theme regularly discussed among those who care for
      patients. The current approach is in favor of the psychological interpretation of
      this distress. This approach is obviously pertinent, but could be widened to a
      more sociological vision: is the demand that society places on medicine
      excessive? THE SEARCH FOR AUTONOMY: The demand of the society emerges in a social
      universe that privileges the autonomy of the individual. Medicine serves this
      research for autonomy. Techniques, instrumentalization of the body, and the
      search for mastery engender the collective utopia of the perfect body; medicine
      has become a new faith, keeper of potential redemption measures. THE MEDIATOR
      FUNCTION OF CARING STAFF: Part of the caring staff distress is generated by the
      encounter between the utopia of health and the reality of suffering patients. In
      the present context of our society, one of the caring staff's missions is to act
      as mediator between the patient and the experience of the disease, the patient
      and the representation that he/she has of his/her body and health, and society
      and the expectations society projects on medicine.

PMID- 12212511
TI  - [Urinary tract infections due to wide spectrum beta lactamase producing
      enterobacteriaceae].
AB  - OBJECTIVES: The aim of this study was to specify the characteristics of
      enterobacterial urinary infections producing wide spectrum beta-lactamase (WSBL)
      and the management strategies for these patients infected in geriatric wards.
      METHODS: The prevalence, bacteriological characteristics and treatment regimens
      of enterobacterial urinary infections producing WSBL, diagnosed in a geriatric
      department of internal medicine from May 1977 to April 2001, were studied
      retrospectively. RESULTS: Sixty-six enterobacterial urinary infections producing
      WSBL were diagnosed, with 53 (80%) of them acquired in the ward. They represented
      1.6% of admissions and concerned 24 men and 42 women (sex ratio: 0.57), with a
      mean age of 87 years. Their prevalence was of 20 in the 1st year, 11 in the 2nd,
      9 in the third and 26 in the 4th year. The mean duration of hospitalization of
      infected patients was 4.5-fold longer (90 vs. 20 days) and the mortality rate 2
      fold higher (32 vs. 14%). Enterobacter aerogenes were responsible for half (46%)
      of the WSBL urinary infections. The skin was invaded by enterobacteria in 67% and
      the feces in 57% of cases. More than one third of the urinary infections treated
      relapsed, and digestive decontamination was only efficient in half of the
      patients treated. CONCLUSION: This 4-year study emphasizes the limits of
      antibiotherapy in eradicating WSBL-producing enterobacteria and the fact that
      only the strict respect of hygiene by all caregivers (isolation of patients
      exhibiting WSBL and washing-disinfection of the hands between each patient)
      limits the incidence of such infections.

PMID- 12212512
TI  - [Disseminated strongyloidiasis, a rare cause of multiple organ failure].
AB  - INTRODUCTION: Strongyloidiasis is an parasitic intestinal disease, frequent in
      tropical countries and fairly rare in temperate areas under certain conditions.
      Disseminated forms can provoke multivisceral damage. CASE REPORT: A 75 year-old
      woman, hospitalized for occlusion, developed multivisceral (cerebral, renal,
      cardiac pulmonary and hepatic) damage over 48 hours, attributed to
      strongyloidiasis. The diagnosis was confirmed by isolation of larvae in the
      tracheal and gastric aspiration fluids. Treatment combined ivermectin and
      albendazole. COMMENTS: Disseminated stronglyloidiasis is essentially observed in
      immunodepressed patients, under corticosteroids or HTLV1 carriers, although an
      HIV status does not appear to intervene. Larvae can be found in all the organs.
      Death occurs by multivisceral failure in 50 to 70% of cases. Broncho-alveolar
      washing and examination of the gastric fluids is the key to diagnosis. Treatment
      relies on thiabendazole, ivermectin or albendazole, and the symptomatic
      management of all the visceral deficiencies.

PMID- 12212513
TI  - [Infectious spondylitis of the odontoid process].

PMID- 12212514
TI  - [Eosinophilic meningitis on returning from Tahiti].

PMID- 12212515
TI  - [Placebo effect on diastolic, systolic and pulsed arterial pressure].
AB  - THE PLACEBO EFFECT: In controlled clinical trials, use of a placebo has
      demonstrated that the lowering of blood pressure in hypertensive patients under
      medication is associated with a reduction in cardiovascular morbidity and
      mortality. Although a placebo clearly lowers levels of systolic and diastolic
      blood pressure (to varying degrees depending on the measurement used), it does
      not appear to have any effect on the pulse pressure, representing the difference
      between the systolic and diastolic pressures. CENTRAL MECHANISMS: The absence of
      placebo effect on the pulse pressure, demonstrated by controlled studies,
      suggests the activity of central mechanisms (notably bulbar), common to the
      placebo effect and to the control of neurogenic coupling between the heart and
      the large caliber arteries. IN PRACTICE: Since the pulse pressure after the age
      of 60 is a major factor for predicting myocardial infarction, these results
      suggest that modifications in pulse pressure should be more closely studied
      during controlled cardiovascular clinical trials in elderly patients.

PMID- 12212516
TI  - [Polyadenomatoses: type 2 multiple endocrine neoplasms].
AB  - FROM A CLINICAL POINT OF VIEW: Multiple endocrine neoplasia type 2 (MEN2) is an
      autosomal dominant, inherited multiglandular disease with familial and individual
      age-related penetration and variable expression. A medullary thyroid carcinoma
      (MTC) is always concomitant to MEN2 and associated in varying proportion with
      pheochromocytoma (50%) and hyperparathyroidism (5 to 20%). PROGNOSTIC DATA: The
      prognosis of MEN2 is related to the carcinological evolution of MTC, which
      depends mainly on the stage of discovery and the quality of the first surgical
      treatment, emphasizing the need for early diagnosis. THE IMPORTANCE OF THE ERT
      GENE: The identification of mutations in proto-oncogene RET, responsible for the
      various forms of the disease allows subjects at risk in a family circle to be
      identified and early screening of various endocrine damage, notably MTC, should
      be performed. Biological explorations in all persons carrying this mutation would
      permit diagnosis and surgical treatment of the endocrine lesions, before their
      clinical manifestation.

PMID- 12212517
TI  - [How can the quality of antibiotic therapy be improved in health care centers?
      Quality = preserving collective value without sacrificing the individual
      importance of the patient].

PMID- 12212518
TI  - [Parkinson disease and the noradrenaline system].

PMID- 12212519
TI  - [Addiction medicine--the "delayed specialty"?].

PMID- 12212520
TI  - [Genetics of bipolar affective disorders. Current status of research for
      identification of susceptibility genes].
AB  - Bipolar affective disorder is a highly heritable condition, as evidenced by twin,
      family, and adoption studies. However, the mode of inheritance is complex and
      linkage findings have been difficult to replicate. Despite these limitations,
      consistent linkage findings have emerged for several chromosomes, notably 3p12
      p14, 4p16, 10q25-q26, and 12q23-q24. Three additional areas, 13q32-q33, 18p11
      q11, and 22q12-q13, have shown linkage in regions that appear to overlap with
      linkage findings in schizophrenia. These chromosomal regions might harbour genes
      that contribute to the development of bipolar affective disorder. Recent
      candidate gene studies include some positive results for the serotonin
      transporter gene (5-HTT) on 17q11-q12 and the catechol-O-methyltransferase gene
      (COMT) on 22q11. New methods are being developed for linkage disequilibrium
      mapping and candidate gene approaches. One can be optimistic that over the next
      few years bipolar susceptibility genes will be identified.

PMID- 12212521
TI  - [Molecular aspects of antidepressive therapy. Transsynaptic effects on signal
      transduction, gene expression and neuronal plasticity].
AB  - Simple neurotransmitter theories cannot sufficiently explain the mode of action
      of antidepressant drugs. Molecular pharmacological studies demonstrate that
      antidepressive treatment initially modulates the neurotransmitter-receptor
      interaction, subsequently influences signal transduction cascades beyond the
      synapse and gene transcription mechanisms, and ultimately triggers the expression
      of specific target genes. Such genes often code for molecules which play an
      important role in the maintenance of neural and synaptic plasticity. Chronic (but
      not acute) treatment with antidepressants modulates, for example, the cAMP-second
      messenger system and increases the expression of neurotrophic factors.
      Furthermore, antidepressants promote hippocampal neurogenesis. Stress, an
      important risk factor for psychiatric disorders, often induces opposite effects.
      A better understanding of the molecular and cellular effects of stress and
      therapy with psychotropic drugs will stimulate the development of innovative
      treatment strategies for which an optimised antidepressant efficacy with a
      simultaneously improved tolerance is expected.

PMID- 12212522
TI  - [Hypericum perforatum extract in treatment of mild to moderate depression.
      Clinical and pharmacological aspects].
AB  - For many years, hypericum extracts have been used in the treatment of depressive
      disorders. The therapeutical use of these extracts has been predominantly
      justified for a long time by the clinical evidence of efficacy and only partly by
      results of scientific studies. The aim of the present investigation is to perform
      a meta-analysis of the placebo- and verum-controlled studies carried out till
      now, to examine the relevance of hyperforin and hypericin for the clinical
      efficacy of St. John's Wort, to discuss biochemical and pharmacoendocrinological
      studies investigating the mechanism of action, and to describe side effects and
      interactions of hypericum extracts. In particular during recent years,
      methodologically quite sophisticated studies have been performed. The
      comprehensive evaluation of all studies available suggests a significant
      superiority of hypericum extracts over placebo, despite the negative results of
      two recently published American trials, and a therapeutic efficacy comparable to
      that of synthetic antidepressants in mildly to moderately depressed patients.
      Furthermore, it has been suggested in preclinical and clinical studies that the
      content of hyperforin but not of hypericin decisively contributes to the
      antidepressant efficacy of hypericum extracts. Hyperforin has been demonstrated
      in biochemical investigations--like synthetic antidepressants--to inhibit the
      reuptake of the neurotransmitters norepinephrine, serotonin, and dopamine.
      Hypericum extracts can be regarded as well tolerated, and they extend the variety
      of pharmacotherapeutical options in the treatment of depression, especially in
      outpatients. However, interactions in combination treatments are possible by
      interference with the cytochrom P450 system, thereby changing plasma levels of
      other medications.

PMID- 12212523
TI  - [Psychodynamic therapy approaches in depressive disorders. Pathogenesis models
      and empirical principles].
AB  - Targets for psychodynamic psychotherapy are the core conflictual relational mode
      and its consequences for mood, social behaviour, and self image. Libido- and
      conflict-based concepts of the relational mode are increasingly being replaced by
      the concept of intersubjectivity, which includes also nonconflictual, healthy
      modes of relations as a basic human mental task. According to recent mother
      infant interaction research, the psychotherapeutic effect on the relational mode
      can be interpreted in terms of procedural learning rather than insight-oriented
      discourse. The mother-infant paradigm is a particularly suitable research
      paradigm to elucidate unconscious procedural acquisition of mental
      representations of dyadic interactional styles. Procedural learning requires a
      more active corrective style of interacting on the therapist's side, beyond
      abstinence and control of countertransference. Evaluative studies show that
      psychodynamic psychotherapy of depression is nearly as effective as cognitive
      behaviour therapy (CBT) and interpersonal therapy (IPT).

PMID- 12212524
TI  - [Cognitive behavioral therapy as supplement to pharmacotherapy of manic
      depressive disorders. What is the empirical basis?].
AB  - Medications will be always necessary in the treatment of bipolar affective
      disorders. More and more, however, the importance of an adjunctive psychotherapy
      is emphasized. Numerous controlled therapy trials showed that unipolar depressed
      patients can be effectively treated with cognitive behavior therapy (CBT).
      Therefore a literature search was done to check for the empirical evidence
      concerning the efficacy of CBT for bipolar disorders. We conducted a literature
      search using Medline, PsycINFO, and Psyndex, considering all publications dealing
      with the topic "psychotherapy and bipolar disorder" till July 2001. This search
      resulted in 241 articles. Ten percent of these publications were considered to be
      controlled trials. Four studies explicitly tested the efficacy of CBT. Compared
      to standard medical treatment, CBT proved to be efficient concerning symptomatic
      and functional outcome. However, there remain many questions to be answered,
      e.g., if there are differential effects on the course of manic and depressive
      symptoms and how stable the results will be in the long run.

PMID- 12212525
TI  - [Fatal poisonings with antidepressive drugs and neuroleptics. Analysis of a
      correlation with prescriptions in Vienna 1991 to 1997].
AB  - As a result of the increasing use of selective serotonin reuptake inhibitors
      (SSRI), the number of antidepressants (AD) prescribed in Vienna doubled from 1991
      to 1997. In the same period, autopsies and chemical analyses performed at the
      Institute of Forensic Medicine, University of Vienna, revealed a total of 164
      fatal intoxications by means of AD. In this study, the number of fatal
      intoxications per million defined daily doses prescribed was determined and
      referred to as the fatal toxicity index (f-index). For both single- and multiple
      substance intoxications, it proved to be significantly (p < 0.001) lower with
      SSRI than with tricyclic antidepressants (TCA). Single-substance intoxications (n
      = 30) were seen exclusively in TCA. Concerning neuroleptics (NL), the increase in
      prescriptions observed in the study period (plus 30%) was less pronounced, and
      they were found to be involved in 85 fatal intoxications. Also in NL, those of
      the tricyclic type (TCNL) showed a significantly (p < 0.001) higher f-index than
      other groups. Out of a total of 17 single-substance intoxications, 14 were caused
      by TCNL and none by butyrophenones or haloperidol. The present study demonstrates
      that the prescription of TCA or TCNL involves a relatively high risk of fatal
      intoxication.

PMID- 12212527
TI  - [Chronic course and psychosocial disability caused by depressive illnesses in
      general practice patients during a one year period. Results of a study by the
      World Health Organization].
AB  - As part of an international WHO study on psychological disorders in primary
      health care, patients were examined for mental disorders and especially
      depression and social disability in the course of 1 year. Depression is common in
      primary care (8.6%) and frequently associated with recurring or chronic courses
      (33.3%). Depression at baseline leads to a 100% increase of lost working days
      (3.2 per month) 1 year later as compared to patients without depression (1.7).
      The diagnosis of depression at baseline poses a greater risk for a relevant and
      lasting psychosocial disability (28.2%) than e.g. chronic somatic illnesses
      (8.6%). Even the diagnosis of a subthreshold depression leads comparatively to a
      higher degree of psychosocial disability (15.6% of patients) and days of
      absenteeism at work during the last month (2.9 days).

PMID- 12212526
TI  - [Seasonal affective depression in 2 German speaking university centers: Bonn,
      Vienna. Clinical and demographic characteristics].
AB  - Six hundred ten patients with seasonal affective disorder (SAD) were diagnosed
      and treated at the university hospitals for psychiatry in Bonn, Germany (1989
      1992) and Vienna, Austria (1993-2001). The aim of this study was to compare our
      sample with other SAD populations in the literature and to investigate
      differences between the two study locations. We found female:male sex ratios of
      5.0:1.0 in unipolar depressives and 1.5:1.0 in patients with bipolar affective
      disorder. Of our patients, 21.7% suffered from bipolar II disorder, and 1.3% were
      diagnosed as having bipolar I. Our patients obtained a mean global seasonality
      score (GSS) of 15.4. Women had a higher GSS than men (t = 2.127, P = 0.035), and
      Viennese patients had higher scores than patients in Bonn (t = 3.104, P = 0.002).
      Totals of 66.3% of all patients suffered from atypical depression and 17.8% from
      melancholic depression. Patients with atypical depression were more frequent in
      Vienna, whereas patients with melancholic depression predominated in Bonn (chi 2
      = 54.952, df = 2, P < 0.001). The demographic and clinical characteristics of the
      patients described in this article confirm the findings of other epidemiological
      investigations obtained in non-German-speaking samples.

PMID- 12212528
TI  - [Prevalence, detection and prescribing behavior in depressive syndromes. A German
      federal family physician study].
AB  - This study examines the prevalence of depressive syndromes among unselected
      primary care patients as well as doctors' recognition and treatment rates. This
      nationwide study included a total of 20,421 patients attending their primary care
      doctors (n = 633) on the study's target day. Patients received a self-report
      questionnaire including the depression screening questionnaire (DSQ) to provide
      diagnoses of depressive disorders according to the criteria of DSM-IV and ICD-10.
      These data were compared to the doctor's evaluation form for each patient to
      assess the physician's diagnostic decision, assessment of clinical severity, and
      treatment choices. The findings confirm the high prevalence of depressive
      syndromes in primary care settings (11.3%) and underline the particular challenge
      posed by a high proportion of patients near the diagnosis threshold. Although
      recognition rates among more severe major depressive patients (59%) as well as
      treatments prescribed appear to be more favourable than in previous studies, the
      situation in less severe cases and the high proportion of doctors' definite
      depression diagnoses in patients who do not fulfill the diagnostic criteria still
      raise significant concerns.

PMID- 12212530
TI  - [Attitude of the population to schizophrenic patients in 6 federal German large
      cities].
AB  - In a research project of the German Research Network on Schizophrenia, public
      attitudes towards people with schizophrenia were studied within a public
      education project. In six German cities, 7,246 persons aged 16 or older were
      interviewed in a telephone survey. Knowledge of schizophrenia, social distance,
      and proposals for activities to improve the public acceptance of mentally ill
      persons were inquired. Most of the persons interviewed expressed positive
      attitudes towards people with schizophrenia. Better public education about mental
      illnesses and the opportunity for closer contact to mentally ill persons were
      rated as important to improve the public acceptance of these individuals.

PMID- 12212529
TI  - [Knowledge and attitude of the general public regarding symptoms, etiology and
      possible treatments of depressive illnesses].
AB  - Within the German research network on depression, the Nuremberg Alliance against
      Depression aims at informing the public about depressive illness and preventing
      suicidality by carrying out a city-wide information campaign. Before the
      prevention program started, public attitudes and knowledge had been assessed in a
      public opinion survey in Nuremberg and in a control region. A total of 1426
      randomly chosen inhabitants of Nuremberg and Wurzburg completed a computer
      assisted telephone interview during November and December 2000. They were asked
      about their knowledge and attitudes towards symptoms, causes, and treatment of
      depression. No relevant differences between Nuremberg and Wurzburg were found.
      Depression is regarded as a serious illness. People seemed to be more
      knowledgeable as compared to the results of earlier surveys, but there are still
      important information deficits. This is especially true for males over 60, who
      show unfavorable attitudes. Eighty percent of the population consider
      antidepressants to be addictive, and 69% were convinced that the use of
      antidepressants would lead to personality changes. Future information campaigns
      should aim at describing depression as an often chronic disease similar to
      hypertonia or diabetes. Public knowledge about antidepressants must be improved.

PMID- 12212531
TI  - [Alcohol problems in adolescence with reference to high risk children of
      alcoholic parents. Results of a family study in Mecklenburg Vorpommern].
AB  - In earlier studies, children of alcoholics (COAs) reported more alcohol and drug
      problems and higher levels of maladaptive behaviour and psychiatric distress than
      non-COAs. However, increased exposure to drugs and alcohol among COAs does not
      fully explain this phenomenon. In our family-based study design, we were able to
      investigate specific risk factors for alcohol problems in adolescence. In a first
      step, we compared a variety of psychosocial risk factors in 90 adolescents (12-18
      years of age) from families with at least one alcohol-abusing parent with those
      of 90 adolescents of parents without alcohol disorders. In a second step, we
      investigated the meaning of all included risk factors for alcohol problems of the
      adolescents. Our results give some support to the existence of a lower extent of
      emotional warmth and support by parents of children in the COA sample. Moreover,
      males of the COA group reported more parental rejection and higher values on
      measures of attention problems and anxiety/depression than controls, whereas
      there were no such differences between females of the COA group and their control
      counterparts. Additionally, logistic regression analysis revealed that only the
      membership in a substance-using peer group and higher age are important risk
      factors for alcohol problems during adolescence. Considering our results, it is
      of great importance (a) to identify families at risk at the earliest possible
      stage and (b) to develop intervention and prevention programs further for parents
      and children to increase social competence and protect children at risk from
      later alcohol abuse.

PMID- 12212532
TI  - [Clinical aspects of puerperal psychoses. Review with 3 case examples].
AB  - Psychic disturbances in the post-partum period are divided into the postpartum
      blues, postpartum depression, and postpartum psychoses. The latter are severe
      endogenous psychoses which mostly fulfill the diagnostic criteria for cycloid
      psychoses according to Leonhard. Based on three case reports, characteristic
      symptoms, the phasic clinical course with remissions, and distinct etiological,
      therapeutic, and forensic aspects of cycloid psychoses in the post-partum period
      are discussed. The high relapse rate of approximately 50% in patients at risk
      requires intensive psychiatric care in the peripartal period. In particular, the
      possibility of a prophylactic treatment of patients at risk with lithium
      immediately after delivery is emphasized. However, this sophisticated therapeutic
      strategy requires close cooperation between gynecologists and psychiatrists.

PMID- 12212534
TI  - ["Accentuated disposition"--rediscovery of an important concept in personality
      psychology].

PMID- 12212533
TI  - [Acute liver failure in nefazodone therapy? A case report].
AB  - Antidepressant-induced hepatotoxicity is generally considered of minimal clinical
      importance and is not well recognized. We report on a patient with recurrent
      major depression who was treated with nefazodone. Six weeks after initiation of
      therapy with nefazodone, he developed fatal liver failure. After cessation of the
      drug, the patient did not recover. He underwent liver transplantation but
      unfortunately died.

PMID- 12212535
TI  - ["886a": an absolutely required psychiatric fee number. Psychiatric psychotherapy
      number for adults analog to 886 for children and adolescents].

PMID- 12212536
TI  - [Hemmo Muller-Suur (1911-2001). Remarks regarding the title picture].

PMID- 12212537
TI  - Herpes virus infections, HIV, and disease progression.

PMID- 12212538
TI  - Herpes virus infections, HIV, and disease progression. Guarded optimism.

PMID- 12212539
TI  - Herpes virus infections, HIV, and disease progression. Recommended, not required.

PMID- 12212540
TI  - Herpes virus infections, HIV, and disease progression. Wait and see.

PMID- 12212541
TI  - Therapeutic decision making in 1997. Roundtable discussion of five cases.

PMID- 12212542
TI  - Access to HIV medical care: a roundtable.

PMID- 12212543
TI  - Cerebral physiological and biochemical changes during vasogenic brain oedema
      induced by intrathecal injection of bacterial lipopolysaccharides in piglets.
AB  - BACKGROUND: The objective of the study was to evaluate biochemical and
      physiological changes in an experimental model of vasogenic brain oedema
      utilising techniques also used in routine neurointensive care. METHOD: 32 piglets
      were randomised to control or experimental group. The latter received an
      intrathecal injection of lipopolysaccharide (LPS) from E. coli (LPS group).
      Intracranial pressure (ICP)and mean arterial pressure (MAP) were measured
      continuously. Intracerebral microdialysis was used for analysing interstitial
      levels of glucose, pyruvate, lactate, glutamate, glycerol and urea every 30 min.
      Repeated calculations of mean hemispheric CBF were performed utilising an
      extracranial scintillation detector and Intra-carotid injection of (133)Xe.
      Cerebral specific gravity was measured and the brains were fixed for histological
      examinations. FINDINGS: After LPS injection ICP increased reaching a plateau
      phase after 4-7 hours and CBF increased by 46%. Histological examination showed
      inflammation with pronounced extravasation of granulocytes. A significant
      decrease in brain specific gravity (p =0.022) was obtained. LPS caused a
      significant decrease in cerebral interstitial concentration of glucose (p =
      0.0035), and significant increases in lactate concentration (p = 0.002) and
      lactate/pyruvate ratio (p = 0.0017). A small but significant increase in
      glutamate was obtained (p = 0.0219). Glycerol did not change significantly.
      INTERPRETATION: Intrathecal LPS caused an inflammatory reaction with
      extravasation of granulocytes, increased blood-brain barrier permeability and
      cerebral oedema. Biochemical analyses indicate increased glycolysis but no signs
      of cell membrane degradation.

PMID- 12212544
TI  - Anaplastic progression in low grade glioneural neoplasms.

PMID- 12212545
TI  - Do neutrophils contribute to myocardial reperfusion injury?

PMID- 12212547
TI  - For: Can ROI methodology/normalised tissue activities be used instead of absolute
      blood flow measurements in the brain?

PMID- 12212546
TI  - Imaging expression of adenoviral HSV1-tk suicide gene transfer using the
      nucleoside analogue FIRU.
AB  - Substrates for monitoring HSV1-tk gene expression include uracil and
      acycloguanosine derivatives. The most commonly used uracil derivative to monitor
      HSV1-tk gene transfer is 1-(2-fluoro-2-deoxy--D-arabinofuranosyl)-5
      [*I]iodouracil (fialuridine; I*-FIAU), where the asterisk denotes any of the
      radioactive iodine isotopes that can be used. We have previously studied other
      nucleosides with imaging properties as good as or better than FIAU, including 1
      (2-fluoro-2-deoxy--D-ribofuranosyl)-5-[*I]iodouracil (FIRU). The first aim of
      this study was to extend the biodistribution data of 123I-labelled FIRU.
      Secondly, we assessed the feasibility of detecting differences in HSV1-tk gene
      expression levels following adenoviral gene transfer in vivo with 123I-FIRU. 9L
      rat gliosarcoma cells were stably transfected with the HSV1-tk gene (9L-tk+).
      123I-FIRU was prepared by radioiodination of 1-(2-fluoro-2-deoxy--D
      ribofuranosyl)-5-tributylstannyl uracil (FTMRSU; precursor compound) and purified
      using an activated Sep-Pak column. Incubation of 9L-tk+ cells and the parental 9L
      cells with 123I-FIRU resulted in a 100-fold higher accumulation of radioactivity
      in the 9L-tk+ cells after an optimum incubation time of 4 h. NIH-bg-nu-xid mice
      were then inoculated subcutaneously with HSV1-tk (-) 9L cells or HSV1-tk (+) 9L
      tk+ cells into both flanks. Biodistribution studies and gamma camera imaging were
      performed at 15 min and 1, 2, 4 and 24 h p.i. At 15 min, the tumour/muscle,
      tumour/blood and tumour/brain ratios were 5.2, 1.0 and 30.3 respectively. Rapid
      renal clearance of the tracer from the body resulted in increasing tumour/muscle,
      tumour/blood and tumour/brain ratios, reaching values of 32.2, 12.5 and 171.6 at
      4 h p.i. A maximum specific activity of 22%ID/g tissue was reached in the 9L-tk+
      tumours 4 h after 123I-FIRU injection. Two Ad5-based adenoviral vectors
      containing the HSV1-tk gene were constructed: a replication-incompetent vector
      with the transgene in the former E1 region, driven by a modified CMV promoter,
      and a novel replication-competent vector with the HSV1-tk gene in E3 driven by
      the natural E3 promoter. The human glioma cell lines U87MG and T98G were infected
      with a multiplicity of infection (m.o.i.) of 10. Forty-eight hours later the
      cells were incubated with 123I-FIRU and radioactivity was measured in a gamma
      counter. We found significantly higher levels of radioactivity in both cell lines
      following infection with the replication-competent vector (P<0.001). NIH-bg-nu
      xid mice were then inoculated subcutaneously with U87MG cells. Tumours
      (approximately 1,000 mm3) were injected with 108 and 109 Infectious Units (I.U.)
      of either vector. After 48 h, the tracer was injected, followed by gamma camera
      imaging and direct measurement of radioactivity in the tumours at 4 h p.i. Images
      and direct measurements indicated increased uptake of tracer with higher I.U. and
      also demonstrated increased accumulation of tracer in the tumours treated with
      the replication-competent adenoviral vector (P=0.03). These results demonstrate
      that 123I-FIRU in combination with HSV1-tk is a valuable tracer for in vivo
      monitoring of adenoviral gene transfer.

PMID- 12212548
TI  - Can normalized tissue activities be used instead of absolute blood flow
      measurements in the brain? [corrected].

PMID- 12212550
TI  - Scintigraphy of the small intestine: a simplified standard for study of transit
      with reference to normal values.

PMID- 12212549
TI  - Which attenuation coefficient to use in combined attenuation and scatter
      corrections for quantitative brain SPET?

PMID- 12212551
TI  - (99m)Tc-HDP uptake in costal cartilage representing a metastasis from an NSCLC.

PMID- 12212552
TI  - Familial glucocorticoid deficiency syndromes.

PMID- 12212553
TI  - JMM--past and present. Invited commentary on A. Blaschko: alopecia areata and
      trichorrhexis.

PMID- 12212554
TI  - Stand and be counted.

PMID- 12212555
TI  - Nonpainful phantom sensation, illusory limb movement in a patient with dorsal
      myelitis. Neuropathological and SPECT findings.

PMID- 12212556
TI  - Prosopagnosia after unilateral right cerebral infarction.

PMID- 12212557
TI  - Fibrocartilaginous embolisation of the spinal cord in a 7-year-old girl.

PMID- 12212558
TI  - Analysis of the exon 1 polymorphism in the Tau gene in transmissible spongiform
      encephalopathies.

PMID- 12212559
TI  - Effects of antiretroviral therapy in patients with Charot-Marie-Tooth disease
      type 1A.

PMID- 12212560
TI  - Adult-onset subacute sclerosing panencephalitis presenting as a degenerative
      dementia syndrome.

PMID- 12212561
TI  - Laza K. Lazarevic (1851-1891).

PMID- 12212562
TI  - Astrocytes instruct stem cells to differentiate into neurons.

PMID- 12212563
TI  - Ignoring our roots.

PMID- 12212564
TI  - Bibliography. Current world literature. Clinical trials.

PMID- 12212565
TI  - Bibliography. Current world literature. Hypertension.

PMID- 12212566
TI  - An evaluation of the quality of herbal product information provided by health
      food store retailers and pharmacists in a Canadian city.

PMID- 12212567
TI  - Bone status after pregnancy and during lactation.

PMID- 12212568
TI  - Evaluation of an online postgraduate education programme.
AB  - Information technology supporting training in medicine is unstructured and
      critical evaluation of its use is lacking. The objective of the paper was the
      evaluation of an Internet-delivered postgraduate training course in medicine. The
      work took place in the Division of Obstetrics and Gynaecology and Institute for
      Learning and Research Technology, University of Bristol. Postgraduate trainees
      were invited to participate in an Internet delivered training programme over 5
      months. Tutors and the participants were interviewed, inter-participant emails
      were collected and post-course evaluation of all trainees was undertaken at 2 and
      6 months. Of 18 enrolled participants, 11 actively participated (mean: five each
      month). Participants were more likely to view other participants' responses or
      tutor feedback than respond themselves. The Internet is a suitable medium for
      courses of this nature. Satisfaction levels with the content of the course and
      with the medium used were high. Constructive criticism was incorporated into
      future courses.

PMID- 12212569
TI  - Supporting individual tutors: a pilot in Australian paediatrics.

PMID- 12212571
TI  - Death--Suicide--Euthanasia--Aiding and abetting--Human rights--Suicide Act 1961
      (UK)--European Convention on Human Rights. Pretty v Director of Public
      Prosecutions [2001] UKHL61.

PMID- 12212572
TI  - Clinical quiz. Complications of small bowel resectioning.

PMID- 12212573
TI  - What works, and what really works.

PMID- 12212574
TI  - Commentary on "Functional MRI and the study of human consciousness" by Daniel
      Lloyd.

PMID- 12212575
TI  - Trials and tribulations of the two doctor family.

PMID- 12212576
TI  - Management training for the aspiring consultant.

PMID- 12212578
TI  - Junior doctors should be given more opportunities to participate in management.

PMID- 12212579
TI  - Getting a work permit for the United Kingdom as a doctor from outside the
      European Union.

PMID- 12212580
TI  - [Advice of the French Superior Council on Public Health (section on transmissible
      diseases) relative to vaccination by heptavalent pneumococcal conjugate vaccine
      (Prevanar). Meeting of March 8, 2002].
AB  - This article is the full-length text (including arguments and recommendations)
      written by the Conseil Superieur d'Hygiene Publique de France, in its session of
      march 8th 2002, expressing its opinion on the immunization policy with the
      heptavalent pneumococcal conjugate vaccine (Prevenar).

PMID- 12212581
TI  - Hypopharyngeal neurinoma: report of two cases.
AB  - Hypopharyngeal neurinoma: report of two cases. Acta Otolaryngol 2002; Suppl 547:
      100-103. Hypopharyngeal neurinoma is a very rare disease and we found reports of
      only seven cases in the literature. Laryngomicrosurgery (LMS) and lateral neck
      exploration are two operating methods for hypopharyngeal neurinoma. Of the seven
      reported cases, the operating method was mentioned in six: two were operated on
      using LMS and four using the neck exploration method. It is necessary to select
      the operating method based on the size of the tumor, the existence of a stem, the
      risk of bleeding, etc. It is difficult to trace the original nerve of the tumor
      and this could not be done conclusively in the previous reports.

PMID- 12212582
TI  - A case of extramedullary plasmacytoma of the larynx.
AB  - An 84-year-old male with a complaint of hoarseness was examined. A mass lesion
      was recognized in the false vocal fold. The tumor was excised and found to
      consist of atypical plasmacytes. Immunopathological examination revealed that
      leukocyte common antigen (CD45), UCHLI (CD45RO), CD3 and L26 (CD20) were negative
      and that CD79 and Vs38C were positive. Neither uric Bence-Jones protein nor serum
      M-protein were observed. No other bony abnormalities were recognized on X-ray
      examinations including both bone and Ga scintigraphy. No atypical plasmacyte
      infiltration was observed in bone marrow. Our final diagnosis was extramedullary
      plasmacytoma of the larynx. Radiotherapy was performed following surgery. The
      tumor did not progress to multiple myeloma and no recurrence has been observed
      after 2 years.

PMID- 12212583
TI  - Speech rehabilitation after total laryngectomy.
AB  - The outcome of speech therapy for 65 laryngectomees at Kitasato University
      Hospital is reported and what needs to be done in order to establish a better
      system for laryngectomee rehabilitation in Japan is discussed. Of the 65
      patients, 53 were trained for both esophageal and electrolarynx speech, 8 for
      electrolarynx speech only and 4 for esophageal speech only. Of the 57 patients
      who were trained for esophageal speech, 38 continued the training for a period of
      > 6 months. Of these 38, 36 (94.7%) could produce one-syllable sounds at the
      first session. For the production of 5-6 syllables, a median of 6 sessions was
      necessary for the total laryngectomee group and 10 sessions were necessary for
      the pharyngo-laryngo-esophagectomee group but the difference was not significant.
      The study showed that for the production of a single esophageal sound the
      training period in our hospital was much shorter than that reported in other
      Japanese studies. Of the 65 patients, 27 (41.5%) acquired practical esophageal
      speech and 59 (90.8%) acquired either esophageal or electrolarynx speech. Six
      (9.2%) could not acquire any alaryngeal speech and this percentage was lower than
      that reported in other studies from Japan (12.5-33%) and from other countries
      (8.5-40%).

PMID- 12212584
TI  - Clinical impact of using chemoradiotherapy as a primary treatment for
      hypopharyngeal cancer.
AB  - Eighty-eight patients with hypopharyngeal cancer who received chemoradiotherapy
      as the primary treatment between 1979 and 1997 were investigated. Forty-six
      patients who received surgery as the primary treatment were analyzed as a control
      group. There were no statistically significant differences regarding TN
      classification, tumor stage, tumor site, age or sex between the radiation and
      surgery groups. The 5-year cumulative survival rate of primary chemoradiotherapy
      was 47% and this did not differ significantly from that for the primary surgery
      group. The larynx was preserved in 74% of cases in the primary chemoradiotherapy
      group, a far better preservation rate than that in the surgery group. After
      primary chemoradiotherapy, complete remission (CR) was observed in 59% of cases
      and the average period of CR was 38 months. Among patients with residual tumor, a
      salvage operation was employed in 31 cases, 13 patients refused to receive
      surgery and 8 were inoperable. A salvage operation was performed in 35% of all
      cases and the 5-year cumulative survival rate was 50%. Based on the 5-year
      survival, primary CR, salvage and laryngeal preservation rates, we conclude that
      chemoradiotherapy is a good primary treatment for hypopharyngeal cancer.

PMID- 12212585
TI  - Expression of Epstein-Barr virus-encoded small nuclear RNA 1 in Japanese
      nasopharyngeal carcinomas.
AB  - An examination was made of the incidence of the Epstein-Barr virus (EBV) genome
      and its exact localization in 39 cases of nasopharyngeal carcinoma (NPC) in
      Japanese patients by means of in situ hybridization (ISH) with a digoxigenin
      labeled Epstein-Barr virus-encoded small nuclear RNA 1 (EBER1) oligonucleotide
      probe. Hybridization signals were observed in the nucleus of tumor cells in all
      39 NPCs, including keratinizing carcinomas. The signals varied greatly in
      intensity from case to case and even from cell to cell in the same tumor, but
      were recognized in most tumor cells in each case. Signals could occasionally be
      seen in limiting number of infiltrating small lymphocytes but were absent in all
      tumors of the tongue, midpharynx and hypopharynx. Combined immunohistochemistry
      ISH studies indicated that EBER1 signals were restricted to tumor cells positive
      for cytokeratin. As a result of this study, it is now possible to perform large
      scale retrospective analyses using routine formalin-fixed, paraffin-embedded
      tissue sections and to combine ISH for the EBV genome with immunohistochemistry
      for cytokeratin to determine the epithelial features of EBV genome-possessing
      cells. All NPCs were clearly shown to be EBV-infected, thus indicating that EBV
      is essential for the oncogenesis of NPCs.

PMID- 12212586
TI  - Cemento-ossifying fibroma of maxillary and sphenoid sinuses: case report and
      literature review.
AB  - We report a case of cemento-ossifying fibroma (COF) involving the maxillary and
      sphenoid sinuses and review the literature in order to study the clinical
      features, imaging findings and histopathologic characteristics of COF. Special
      care was taken to distinguish this lesion from cemento-osseous dysplasia (COD).
      It is almost inevitable that differential diagnosis of COD and COF will be
      complicated by the fact that some pathologic features are shared by both lesions.
      A combined study incorporating clinical, radiographic and pathologic findings is
      important in order to ensure an accurate diagnosis. Postoperative follow-up is
      essential, especially in cases where incomplete removal of the COF was performed.

PMID- 12212587
TI  - Treatment of maxillary sinus carcinoma: clinical results using the Kitasato
      modality.
AB  - The conventional therapeutic regimen for maxillary sinus carcinoma consists of
      dissection of the maxilla, full-dose irradiation and extensive chemotherapy.
      However, the results obtained with this treatment are often poor. Even when
      patients recover, their quality of life is significantly reduced as a result of
      deformity of facial structures and swallowing and articulation dysfunctions. A
      retrospective analysis of 68 patients with maxillary sinus carcinoma treated with
      the Kitasato modality between 1975 and 1999 was conducted. All patients underwent
      pergingival maxillary sinus surgery combined with pre- and postoperative
      irradiation therapy with standardized total doses of 16 Gy; the postoperative
      irradiation was given in combination with regional intra-arterial infusion
      chemotherapy administered via the superficial temporal artery. All visible tumor
      lesions were removed where possible in order to preserve or facilitate cellular
      immunity after surgery. The cumulative 5-year survival rates were 85.7% for Stage
      II patients, 88.1% for Stage III, 76.6% for Stage IVA and 75.% for Stage IVB.

PMID- 12212588
TI  - Carcinoma of the nasopharynx: analysis of treatment results in 91 patients.
AB  - The outcome of 91 patients (69 males, 22 females; age range 16-82 years) with
      nasopharyngeal carcinoma treated in our hospital between 1971 and 1999 was
      evaluated. Factors that appeared to influence prognosis were assessed using the
      Kaplan-Meier method. The cause-specific cumulative 5-year survival rate for the
      entire study population was 61.2%. The 1997 International Union Against Cancer
      classification was used for disease staging. The 5-year survival rates were as
      follows: 66.7% (n = 3) for Stage I; 100% (n = 2) for Stage IIA; 90.9% (n = 11)
      for Stage IIB; 78.8% (n = 25) for Stage III; 53.0% (n = 29) for Stage IVA; 37.5%
      (n = 16) for Stage IVB; and 20.0% (n = 5) for Stage IVC. The disease-free
      cumulative 3-year survival rates of the patients classified based on initial
      therapy were as follows: radiation alone, 50.0% (n = 28); combined radiotherapy
      and chemotherapy that included an undefined anti-cancer drug, 67.2% (n = 39);
      combined radiotherapy and chemotherapy that included carboplatin (CBDCA), 92.3%
      (n = 19). These results showed a statistically significant difference (p = 0.043;
      log-rank test). Stage IVC patients were excluded from the analysis. We conclude
      that combined therapy, including chemotherapy with CBDCA, is necessary for the
      treatment of nasopharyngeal carcinoma. In terms of radiation therapy, a field
      covering the bilateral cervical regions seemed to produce favorable results, even
      if cervical node metastasis was not confirmed by palpation at the first hospital
      visit. Key words: carboplatin, chemotherapy,

PMID- 12212589
TI  - Treatment effects in patients with squamous cell carcinoma of the oral cavity.
AB  - A total of 221 patients (155 males, 66 females; stage I, n = 55: stage II, n =
      58; stage III, n = 57; stage IV, n = 51) with squamous cell carcinoma of the oral
      cavity were studied. Tumor localization was as follows: cancer of the tongue, n =
      161; cancer of the oral floor, n = 28; cancer of the hard palate, n = 12; cancer
      of the buccal mucosa, n = 11; and cancer of the gingiva, n = 9. In order to
      compare the effect of different treatments, three major treatment groups were
      defined, namely a surgery group, a radiotherapy group and a combination treatment
      group. Five-year cumulative survival rates showed significant differences between
      stage classifications (stage I = 91%, stage II = 73%, stage III = 63%, stage IV =
      47%; p < 0.01) but not between tumor sites. The 5-year cumulative survival rate
      was highest for oral floor cancer (80%). In the early-cancer group, the 5-year
      cumulative survival rate for the surgery group (92%) was significantly higher (p
      < 0.05) than those for both the radiation (69%) and combination (71%) groups. In
      the advanced-cancer group, the 5-year cumulative survival rate for the surgery
      group (74%) was significantly higher (p < 0.05) than those for both the radiation
      (37%) and combination (51%) groups. No significant difference in regional control
      rates was observed between the treatment groups. Five-year regional control rates
      were 86% for cervical untreated patients with T1N0 tumors and 60% for cervical
      untreated patients with T2N0 tumors. Fourteen N0 cases were treated with neck
      dissection. Cervical metastasis was found pathologically in 2/14 (14%) of these
      cases. The 5-year survival rate for patients with cervical recurrences after
      primary tumor resection was 70% (n = 15). In contrast, the 5-year survival rate
      for patients with both primary tumor resection and neck dissection was 74% (n =
      14) but no significant difference was observed between these 2 groups.

PMID- 12212590
TI  - Assessment of oropharyngeal cancer.
AB  - The records of 87 patients with squamous cell carcinoma of the oropharynx,
      treated between 1971 and 1998 at Kitasato University Hospital, were reviewed with
      the aim of investigating further directions for oropharyngeal cancer treatment.
      The patients were divided into four major treatment groups: a radiotherapy group;
      an operation group; a simultaneous chemoradiotherapy group; and a combination
      treatment group. The 5-year cumulative survival rates for Stages I-IV were 75%,
      78%, 68% and 41%, respectively. None of the T4 cases survived for > 5 years. The
      survival rates of patients with anterior and posterior wall cancers were higher
      than those with lateral and superior wall cancers. All patients in the operation
      group survived for 5 years. The survival rates for the combination treatment,
      radiotherapy and chemoradiotherapy groups were 80%, 57% and 52%, respectively.
      The 5-year cumulative local control rates for T2-T4 tumors were 61%, 58% and 0%,
      respectively. The combination therapy (80%) and chemoradiotherapy (66%) groups
      had significantly higher local control rates than the radiation group (33%). The
      5-year cumulative regional control rate according to N classification was
      approximately 80%, except for N2 lymph nodes, for which only 60% of patients were
      free of regional recurrences. Approximately 15% of patients with oropharyngeal
      cancer had either distant metastases or double cancer. We conclude from this
      review that simultaneous chemoradiotherapy is a good initial therapy for Stages
      Tl-T3 oropharyngeal cancer. However, for T4 tumors, further combinations of both
      chemoradiotherapy and surgery and the development of new anticancer drugs for use
      in chemoradiotherapy, immunotherapy or gene therapy may be needed.

PMID- 12212591
TI  - Three-dimensional analysis of supracricoid hemilaryngopharyngectomized
      hypopharyngeal cancer.
AB  - The aims of this study were to demonstrate the technical aspects of processing
      high-resolution three-dimensional (3D) images and to describe the value of this
      approach for studying partially removed hypopharyngeal cancer. Supracricoid
      hemilaryngopharyngectomy was conducted in three sinus-type hypopharyngeal cancers
      as a salvage operation. A histopathologic study was conducted in order to fully
      examine the resection margin of the surgical specimens and to ensure the
      credibility of our case selection. The morphological features of each specimen
      were analyzed and demonstrated using 2D and 3D settings. Whole-mount serial
      histological sections were developed from the surgical specimens and 3D images
      were reconstructed based on these sections. In each case the 3D images
      demonstrated the characteristic patterns of cancer extension, such as superior
      extension under the intact epithelium and the formation of multiple skip lesions.
      The overall resection margin was proven to be free of cancer in all three cases.
      In conclusion, 3D study was useful for evaluating the overall resection margin of
      surgical specimens and provided valuable information for use in future follow-up.
      Using this technique, the morphological findings from serial sections are more
      comprehensive and impressive. 3D reconstruction is and will be a crucial modality
      for studying the morphological behavior of hypopharyngeal cancer.

PMID- 12212592
TI  - Limited surgery for cancer of the larynx and hypopharynx: options and
      consequences.
AB  - We reviewed surgical options for laryngeal preservation (limited surgery) in
      laryngeal and hypopharyngeal cancers and the consequences of the options. Of 44
      patients with laryngeal cancer, 11 (25%) received limited surgery and 33 (75%)
      received total laryngectomy. The survival rates were 91% for the limited surgery
      group and 73% for the total (radical) surgery group. Of 31 patients with
      hypopharyngeal cancer, 7 (23%) received limited surgery and 24 (77%) received
      total laryngopharyngectomy. The survival rates were 53% for the limited surgery
      group and 40% for the total (radical) surgery group. The survival rates
      associated with limited surgery were thus better than those for total (radical)
      surgery for cancers of both the larynx and hypopharynx. This was attributed to
      the limited surgery group comprising well-selected patients with confined
      lesions. Organ preservation surgery should be technically simple, reliable in
      terms of its functional impact and, above all, should not jeopardize the
      patient's survival. Supracricoid subtotal laryngectomy with
      cricohyoidoepiglottopexy or cricohyoido-pexy has great potential for laryngeal
      preservation and will become the major limited surgery modality for treating
      cancer of the larynx. Limited surgery, however, needs to be performed with great
      care and is indicated only for very well-selected patients with cancer of the
      hypopharynx.

PMID- 12212593
TI  - Detection of epstein-barr virus in nasal T-cell lymphoma.
AB  - The close relationship between Epstein-Barr virus (EBV) and nasal T-cell lymphoma
      (NTL) has frequently been reported. However, the status of the infection, either
      lytic or latent, is obscure. This study involved 16 patients with NTL. Phenotypes
      of lymphoma cells were examined by immunohistochemical staining using CD3, CD4,
      CD8, CD20 and CD45RO monoclonal antibodies. EBV-encoded small nuclear RNA (EBER)
      1 and EBV NotI tandem repeat region were detected by reverse transcription, using
      a rapid (< or = 60 min) in situ hybridization technique. Tumor cells expressed at
      least one T-cell marker, such as CD3, CD4, CD8 and CD45RO. CD20 was not detected
      in any of the cases. EBER-1 was identified in all cases; no Notl tandem DNA
      repeat was demonstrated. All cases demonstrated a T-cell phenotype. These data
      suggest that NTL is associated with EBV infection in the latent phase.

PMID- 12212594
TI  - Clinical review of Wegener's granulomatosis.
AB  - The prognosis of Wegener's granulomatosis (WG) improved following the
      introduction of immunosuppressant agents. We, however, still experience some
      difficult cases that are resistant to treatment. Early diagnosis and treatment
      may improve the prognosis of WG. We reviewed patients with WG attending the
      Department of Otorhinolaryngology, Kitasato University Hospital. Of the 13
      patients reviewed, 5 are still alive. A definite diagnosis was difficult to make
      without the presence of certain characteristic features. Recently, cytoplasmic
      antineutrophil cytoplasmic antibody (c-ANCA) has gained importance in the
      diagnosis of WG and five of our patients were positive for c-ANCA. Close long
      term follow-up of WG is recommended: remission was observed in two of our
      patients and side-effects of the treatment were identified in four.

PMID- 12212595
TI  - A case of multiple neurofibroma of the larynx and cervical esophagus.
AB  - A case of multiple neurofibroma of the larynx and cervical esophagus is reported.
      Key points concerning the follow-up observations of this case are described.

PMID- 12212596
TI  - Cephalometric and fiberoptic evaluation as a case-selection technique for
      obstructive sleep apnea syndrome (OSAS).
AB  - In order to obtain relatively simple and useful parameters to estimate the
      severity of obstructive sleep apnea syndrome (OSAS), cephalometric and fiberoptic
      studies were performed in 64 clinical cases previously diagnosed with either OSAS
      or snoring. Fourteen cephalometric parameters, 13 parameters derived from
      physical examination and 18 fiberoptic parameters were compared with the apnea
      index (AI), the apnea-hypopnea index and lowest SaO2 values. Statistically
      significant correlations were found between the Al and the shortest linear
      distance from the posterior line of the soft palate to the posterior pharyngeal
      wall measured along a line parallel to the supramentale-Gonion line (PAS
      epipharynx distance), the distance from the mandibular plane to the most anterior
      and superior point on the body of the hyoid bone obtained from cephalometry (MP-H
      distance) and the degree of redundancy of mucosa in the arytenoid/aryepiglottic
      fold obtained from videoendoscopy. An increased Al was observed when the PAS
      epipharynx distance was < 7 mm and there was 100% obstruction in Muller's
      maneuver at the palate level (supine), the MP-H distance was > 27.4 mm and the
      mucosa of the arytenoid/aryepiglottic fold was markedly redundant. As these three
      parameters are relatively easy to obtain on an outpatient basis, it is suggested
      that they could be used in an outpatient setting to provide a good prediction of
      the severity of OSAS.

PMID- 12212597
TI  - Head and neck malignancy statistics at Kitasato University.
AB  - We analyzed and reported on those patients with head and neck (H&N) malignancies
      who had visited our university within the last 30 years. The number of H&N
      patients registered per year has gradually increased with time and approximately
      120 new patients have been registered annually in recent years. Age-adjusted
      morbidity has also increased gradually, from 7.06 to 10.55 per 100,000 citizens,
      in recent years. The population of Sagamihara city has gradually increased in
      parallel over the same period. Cancers of the pharynx, larynx and oral cavity are
      the three major H&N tumors. Squamous cell carcinoma was the most commonly seen
      pathological diagnosis, followed by malignant lymphoma. The 5-year crude survival
      rate for all patients was 50%. It is suggested that improving the survival rates
      of cancers of the oral cavity, nasal cavity and paranasal sinuses should be a
      prerequisite, in order to diminish H&N tumor deaths in Japan. A satisfactory
      survival rate for cancer of the paranasal sinuses has been achieved at Kitasato
      University and it is hoped that our modality will further prevail in the near
      future. Cancer of the oral cavity is visible and can be detected by a simple
      clinical examination. As H&N surgeons it is necessary to educate all physicians
      as to the importance of early detection of H&N tumors. We also need to encourage
      the public to reduce smoking and drinking in order to prevent a further increase
      in the number of H&N patients. Our assertions are based on the fact that the
      number of H&N patients in 2050 is estimated to be three times greater than that
      at present due to the increase in the population of elderly people (assuming the
      morbidity rate remains constant). Key words: alcohol, cancer trends, morbidity,
      predictions, tobacco.

PMID- 12212598
TI  - Clinical review of autopsy cases that succumbed to head and neck malignancies.
AB  - We investigated autopsy cases that had succumbed to head and neck malignancies in
      the light of the relationships between locoregional tumors and distant
      metastasis, between the frequency and site of distant metastasis and between the
      occurrence of locoregional tumors/distant metastasis and the cause of death. Of
      the 203 cases autopsied at the Kitasato University Hospital between 1972 and
      1999, 174 had epithelial tumors and 29 had non-epithelial tumors (malignant
      lymphoma in 20/29). In terms of epithelial tumors, 107 patients (61%) had
      locoregional disease and 101 (58%) exhibited distant metastases; 39 cases (28%)
      had distant metastasis without locoregional tumors. Although the cause of death
      was mostly as the result of locoregional disease, death related to distant
      metastasis was also frequently observed. Of the 20 cases with malignant lymphoma,
      17 had distant metastases and only 2 of them manifested tumors in the primary
      region. All 17 patients with distant metastases showed tumors in the distant
      lymph nodes, with a relatively high occurrence of metastasis to the
      gastrointestinal tract. Key words: cause of death, distant metastasis,
      locoregional tumor.

PMID- 12212599
TI  - Clinical study of T1a glottic-type cancer.
AB  - Laser surgery is indicated for T1a glottic cancer when the tumor is localized in
      the membranous portion without involvement of the anterior commissure or
      cartilagenous portion. Treatment for T1a glottic cancer was reviewed with
      particular attention to indications, prognosis and the pattern of recurrent
      cases. A group treated with laser surgery showed 5-year local control, larynx
      conservation and survival rates of 90.5%, 100% and 100%, respectively.
      Corresponding values for a group treated with radiotherapy were 92.2%, 98.0% and
      100%, respectively. In three cases of recurrence, laser surgery was carried out
      as second and third treatments. These cases met the above-mentioned indications
      for laser surgery at the time of recurrence and re-recurrence. Of the three
      patients, two have survived for > or = 6 years without further recurrences.
      Provided strict selection criteria are applied, laser surgery is indicated in
      some cases of recurrence.

PMID- 12212600
TI  - A comparative study of suturing techniques in microlaryngosurgery.
AB  - Different types of suturing device for microlaryngosurgery were compared. A new
      device was developed based on the results of this comparison, and proved to be
      very useful.

PMID- 12212601
TI  - Malignant fibrous histiocytoma of the nasal cavity and paranasal sinuses: review
      of the last 30 years.
AB  - The clinical and pathologic features of four patients with malignant fibrous
      histiocytoma of the maxillary sinus were studied. All patients were male, with an
      age range of 43-71 years at the time of diagnosis. The main symptoms were pain in
      the facial region, swelling of the cheek and nasal bleeding. Pathologically,
      three patients were subclassified with the striform-pleomorphic type of malignant
      fibrous histiocytoma and one with the myxoid type. All patients were operated on
      and received various combinations of pre- and postoperative irradiation and intra
      arterial chemotherapy given via the temporal artery. In the patient with the best
      prognosis, tumor extension within the maxillary sinus was minimal. Two patients
      developed local recurrences and died. None of the patients developed locoregional
      lymph node or systemic metastases.

PMID- 12212602
TI  - Clinical study of benign lesions in the oral cavity.
AB  - This retrospective study was designed to investigate the detailed clinical
      features of benign oral diseases. A total of 792 patients with benign oral
      lesions were treated at Kitasato University Hospital over a 27-year period.
      Benign oral lesions were classified into nine groups as follows: epithelial
      proliferating lesions (n = 234); fibroma-like lesions (n = 150); cysts and cyst
      like lesions of the minor salivary glands (n = 140); ranulas (n = 64); angiomas
      (n = 62); inflammation/ulcer/granulation lesions (n = 56); pyogenic granulomas (n
      = 44); pleomorphic adenomas (n = 23); and others (n = 19). The characteristics of
      all these benign oral lesions are summarized. We believe that these
      characteristics will be helpful for physicians in their daily clinical
      examinations.

PMID- 12212603
TI  - Clinical review of thyroid malignant tumor.
AB  - We reviewed the files of 120 patients with thyroid malignant tumor treated in our
      department between July 1971 and December 1996. Clinical features, pathological
      diagnosis, radiographic findings, treatment and prognosis were studied. The
      number of patients treated gradually increased over time in both the
      otorhinolaryngology and surgery departments. Papillary carcinoma (n = 101) was
      the most common pathology, followed by follicular carcinoma (n = 16). Both 5- and
      10-year survival rates were 92.7% for the entire group, 93.8% for cases of
      follicular carcinoma and 92.1% for cases of papillary carcinoma. Although thyroid
      tumor is undoubtedly one of the malignant head and neck tumors associated with an
      excellent prognosis, some patients remain resistant to cure in the long term.
      Some tumors are highly malignant and are difficult to control. The management of
      these patients is an important subject of future research.

PMID- 12212604
TI  - Multiple primary malignancies in the head and neck: a clinical review of 121
      patients.
AB  - A total of 121 multiple primary malignancies (quadruple, n = 2; triple, n = 11;
      and double, n = 108) were treated at the Department of Otorhinolaryngology,
      Kitasato University Hospital between July 1972 and December 1998. Of the 108
      patients with double primary malignancies, 18 had synchronous double primary
      malignancies (SDPM), which were defined as occurrence of the index tumor and
      second malignancy within 6 months of each other, and 90 had metachronous double
      primary malignancies (MDPM), which were defined as occurrence of the index tumor
      and the second malignancy separated by a period of > 7 months. MDPM was
      subdivided into MDPM-F (head and neck malignancy occurred as the first tumor; n =
      55) and MDPM-S (head and neck malignancy occurred as the second tumor; n = 35).
      Of the 55 patients with MDPM-F, 27 (49.11%) of the second malignancies were found
      in the digestive tract, 12 in the stomach (21.8%), 8 in the esophagus (14.5%) and
      7 in lower digestive tract tumors (12.7%). The 3- and 5-year survival rates of
      MDPM-F were 79.2% and 62.3%, respectively. Differential diagnosis between
      multiple primary malignancy (MPM) and multicentric tumors is often difficult when
      the lesions involve the oral cavity, pharynx and esophagus. We suggest that it is
      beneficial to follow patients for as long as possible in order to facilitate
      diagnosis of tumor recurrence, metastasis and MPM.

PMID- 12212606
TI  - Cancer of the ear: a report of 22 patients.
AB  - The purpose of this report was to analyze cancer of the ear, with reference to
      its etiology, pathology and classification, by studying 22 patients who visited
      Kitasato University Hospital over a 26-year period. Patients with cancer of the
      ear comprised 0.98% of the 2,244 registered head and neck patients.
      Classifications reported in the literature were utilized to analyze the patient
      data. There was a significant difference in 5-year cumulative survival rates
      associated with cancers arising from the external auditory canal and the middle
      ear, as calculated using the Kaplan-Meier method. Tumor stage was also a
      significant predictor of prognosis. If cancer is suspected, early diagnosis is
      the key to improved prognosis.

PMID- 12212605
TI  - Prognostic factors of head and neck adenoid cystic carcinoma: quantitative
      morphological analysis of 19 cases.
AB  - This quantitative study was prompted by concerns regarding the clinical and
      histopathologic correlation of adenoid cystic carcinoma (ACC). We reviewed the
      clinical and histopathologic data of 19 cases of ACC in the head and neck region
      treated during the last 25 years. An image analyzing system was employed for
      quantitative analysis. Each specimen was observed microscopically at 100 x
      magnification, by two of the authors, the area of pure cellular component in five
      randomly selected fields was measured and the averaged cellular ratio per field
      was calculated as a percentage and then correlated with the behavior of the
      tumor. The cellular ratio was 66% for the 8 patients who died of disease and 47%
      (at 3-year follow-up; n = 9) and 58% (at 10-year follow-up; n = 4) for the 11
      patients who survived without evidence of disease. For all of the patients who
      developed distant metastasis the cellular ratio was > 60%. The results of this
      quantitative study did correlate, to some extent, with the patients' clinical
      behavior. Although non-quantitative clinical and histological criteria of ACC
      have been reported to correlate with clinical behavior, it is important to
      thoroughly understand these criteria and also to combine multiple criteria in
      order to manage head and neck ACC.

PMID- 12212607
TI  - Characteristics of aerobic granules grown on glucose and acetate in sequential
      aerobic sludge blanket reactors.
AB  - Aerobic granules were cultivated in two column-type sequential aerobic sludge
      blanket reactors fed with glucose and acetate, respectively. The characteristics
      of aerobic granules were investigated. Results indicated that the glucose- and
      acetate-fed granules have comparable characteristics in terms of settling
      velocity, size, shape, biomass density, hydrophobicity, physical strength,
      microbial activity and storage stability. Substrate component does not seem to be
      a key factor on the formation of aerobic granules. However, microbial diversity
      of the granules is closely associated with the carbon sources supplied to the
      reactors. Compared with the conventional activated sludge flocs, aerobic granules
      exhibit excellent physical characteristics that would be essential for industrial
      application. This research provides a complete set of characteristics data of
      aerobic granules grown on glucose and acetate, which would be useful for further
      development of aerobic granules-based compact bioreactor for handling high
      strength organic wastewater.

PMID- 12212608
TI  - [Korea's health care policy of the twentieth century].
AB  - This article analyzes the social transformation of Korea's health care policy in
      the twentieth century from a historical perspective. The whole period under the
      research is divided into four stages. In the first stage (1900 - 1945), two major
      health care policies, public hygiene and population control, were a part of
      political strategy for consolidating Japanese colonial dominion over Korea. The
      second stage (1945 - 1960) is characterized by the division of Korean peninsula
      and Korean war that resulted in the vicious cycle between massive poverty and
      social disease. In the third stage (1961 - 1991), military governments considered
      the health care system as a 'carrot' for enhancing national security and
      reinforcing legitimacy of the regime. In the final stage (1992 - 1999), the state
      and civil society have been influential agents in shaping forms and contents of
      health care policy, with the organized medicine relatively neglected.
      Globalization will have more influence on the arena of health care policy in
      which three grants would have to negotiate one another. In addition, the
      organized medicine will have to consider a variety of non-governmental
      organizations (NGOs) as an inevitable counterpart of policy-making process in
      harmonizing the conflicts between public deliberation and professional interests.
      In the next century, health care policy, along with social welfare, environment
      and labor policy agendas would constitute a health-related policy regime in which
      all the participants have to accomplish not medicalization of life but
      socialization of health care and to diminish the inequity in health among a
      variety of social class.

PMID- 12212609
TI  - [One hundred years history of surgery in Korea].
AB  - Introduction of western surgery into Korea is closely related to the introduction
      of western medicine itself into Korea. In December 4th, 1884 Allen, who came to
      Korea as a Missionary Doctor of North Presbyterian Church of America, had a
      chance to treat a patient with severe stab wounds. The patient was a nephew of
      Queen Myungsung. The patient, Min Young Ik was recovered completely. These
      happenings led to the establishment of 'Kwangheywon (renamed to Jejoongwon 2
      weeks later)', the first westernized hospital in Korea. With the great financial
      aids from Severance family, Jejoongwon developed into Severance Hospital and
      Medical School in 1904, and greatly contributed to education of Surgery for
      Korean medical students. Meanwhile Korean Government established the Medical
      School and Hospital to train Korean Doctors in 1899. But the original intentions
      became to be impaired by occupation of Korea by Japan in 1910. As a colony, many
      Japanese Surgeons came to Korea as professors of Kyungsung Medical College, and
      gave only few chances for Koreans to become a professor. On the contrary, several
      surgeons became professors in the private, missionary 'Severance Union Medical
      College'. After liberation from Japanese occupation in 1945, American medical
      system was introduced into Korea, and many surgeons had a chance to be trained in
      America. There was great advancements in the field of surgery, especially of
      neurosurgery, during a tragic Korean War. With the restoration of economy after
      the 1960s, surgery in Korea continued to develop toward an independent and
      consolidated fields of medicine.

PMID- 12212610
TI  - [Hundred years' psychiatry in Korea (1899-1999)].
AB  - The western medical knowledges of the human anatomy and physiology including
      knowledges of central nervous system have probably been introduced into Korea by
      Prince Sohyon Seja in 1645. The authentic education for the western medicine at
      the governmental and private medical schools, however, originated from 1899 and
      the education of mental disease was included in curriculum of Tai-Han-uiwon, the
      governmental medical school before 1910. In 1913 the first department of
      psychiatry (Department of Mental Disease) was established at the Chongdokbu
      uiwon, the clinic of the Japanese colonial government, the former Korean
      governmental hospital which has later developed to the Kyongs ong Imperial
      University Hospital. On the other hand, there was in Severance Hospital Medical
      College, one Australian missionary psychiatrist McLaren, who has served at Paton
      Memorial Hospital in Jinju, Korea from 1911, taught neurology and psychiatry from
      1913 at Severance Hospital Medical College, established psychiatry ward in 1923
      at the Hospital, conducted the ward in humanistic way until 1940. It was the
      German psychiatry which the Japanese psychiatrists have brought to the Korean
      peninsula and it remained as major trends of psychiatry in Korea during the
      Japanese occupation between 1911 and 1945. The academic levels of Kyongsong
      Imperial University in psychiatry as well as the quality of mental care seemed to
      be almost equivocal to the psychiatry in Japan. However, psychiatrists scope of
      social psychiatric issues and of the research interests seemed to be somewhat
      narrow. Due to the political discrimination for the Korean students, the Koreans
      had less opportunity for the promotion at the university than Japanese residents
      in Korea. In 1945, after the end of the Pacific War only about 11 Korean
      psychiatrists were left in Korea, who organized Korean Neuropsychiatric
      Association. The Department of Neuropsychiatry of Seoul National University
      (former Department of Neurology and Psychiatry, Kyongsong Imperial University)
      was the center for psychiatry training. The Korean War (1950-1953) enabled the
      interchanges between. Korean and American military psychiatrist, and motivated
      great change in Korean psychiatry from biologic oriented German descriptive
      psychiatry to the American dynamic psychobiological psychiatry. The German
      educational clinical systems were completely displaced by the American system,
      when internship and residency training system was conducted since 1958. However,
      there were always attempts to integrate old traditional Korean wisdoms into the
      modern psychiatry and to introduce European approaches and knowledges in
      psychiatry. With the rapid industrialization and economic development of the
      country since the late 1960s and the prevailing social defensive attitudes
      towards mentally ill patients of the leaders of the military regimes the increase
      of private asylums appeared where many chronically ill mental patients were kept
      without adequate treatment. The reform of asylums in the mid 1980s was gradually
      proceeded by the government leading consequently to the increase of huge mental
      hospitals in the land. With the democratization of the political situation as
      well as the social welfare policy of the government in the 1990s and with the
      steady stimulation elicited by some NGOs Mental Health Act was enacted in 1995
      and the community mental health centers were increasingly set up in several
      districts. In concern with research activities in psychiatry remarkable
      development in social cultural as well as biological fields are recognized
      especially since in the 1970s academic societies for the subspecialities of
      psychiatry have been organized which cover the various schools of psychotherapy,
      social psychiatry as well as many subspecialities of biological psychiatry. The
      number of training hospitals have been increased as the result, the number of
      psychiatry specialists was increased from 93 in 1956 to 1593 in 1999. KNPA
      (Korean Neuropsychiatric Association) internal and international activities has
      been expanded. Question is however, the quality of services and the quality of
      academic achievement. Gradually, the voice was raised to focus more on the
      quality of research and training activities.

PMID- 12212611
TI  - Apoptosis and taxol therapy.

PMID- 12212612
TI  - Mechanisms of anti-angiogenic tyrosine kinase inhibition on wound healing--the
      obvious and not so obvious.

PMID- 12212613
TI  - Global genomic repair and p53 in a dance after DNA damage.

PMID- 12212614
TI  - Radiosensitivity with Par-4 expression in prostate cancer.

PMID- 12212615
TI  - Participation of BRCA1 in the DNA repair response...via transcription.

PMID- 12212616
TI  - Changes in urinary excretion of deoxypyridinoline in tail-suspended rats: effects
      of a bisphosphonate, YH529.
AB  - Urinary excretion of deoxypyridinoline (D-Pyr) has been shown to be a useful
      marker for bone resorption. In this study, we investigated whether D-Pyr could be
      used to monitor the changes in bone resorption of the hind limb induced by tail
      suspension. Male Wistar rats 5-weeks old were tail-suspended in a metabolic cage
      to unload the hind limbs. The control rats were not suspended. YH529 (YH), an
      inhibitor of bone resorption, or a vehicle (phosphate buffered saline=PBS) was
      administered daily starting 3 days before the commencement of tail-suspension. In
      the non-suspended rats receiving PBS, urinary excretion of D-Pyr did not show any
      significant change during the one-week experimental period. In the non-suspended
      rats receiving YH, D-Pyr excretion significantly decreased on day 5 and 7 when
      compared with that observed on day 0, in accordance with the systemic inhibition
      of bone resorption by YH. In the tail-suspended rats receiving PBS, D-Pyr
      excretion showed a tendency to increase on day 1, which is in agreement with our
      previous report that tail-suspension causes an early (on day 1 of suspension) and
      transient increase in bone-resorption of the hind limbs. In the tail-suspended
      rats treated with YH, the increase in D-Pyr excretion on day 1 was not observed,
      and a significantly lower excretion was noted from day 3 to 7 during the tail
      suspension. It was suggested that D-Pyr excretion might reflect the transient
      increase in hind limb bone resorption induced by tail-suspension. As observed in
      YH treated rats, D-Pyr excretion could serve as a good marker for the inhibition
      of systemic bone resorption.

PMID- 12212617
TI  - Psychological and physiological changes during isolation and confinement: I.
      Group dynamics and member interaction.
AB  - The isolated and confined environment of a laboratory setting was used as one of
      the analogous environments of long-term manned spaceflight. This setting has more
      advantages than the natural one in that the behavioral variables can be easily
      controlled. Thus, a hyperbaric chamber was used in this experiment. The subjects
      were five men from 22- to 26-years old who had never met before the experiment.
      Over a total 5-day isolation and confinement period as well as 2-day pre- and
      post-isolation periods, the subjects were given different kinds of physiological
      and psychological tasks. During these periods their behavior and communications
      were recorded in order to observe when the formation of a group begins and how it
      forms and functions. The formation of a sub-group of three men was observed on
      the third day of isolation, showing strong reciprocal connections among these
      subjects who developed bonds that were quite stable. It is, however, not known
      how this sub-group functioned within the large group, since the experimental
      period was possibly too short.

PMID- 12212618
TI  - Dose response relationship of disturbed migration of Purkinje cells in the
      cerebellum due to X-irradiation.
AB  - Pregnant rats were exposed to 2.0, 2.25 or 2.5 Gy X-irradiation on gestation day
      21. Pups were sacrificed 12 hr after exposure, and on postnatal day 5 (P5), P7
      and P9. Their cerebella were observed immunohistochemically using anti-inositol
      1,4,5 triphosphate (IP3) receptor antibody to identify Purkinje cells. These
      cells were disturbed to migrate and remained in the internal granular layer and
      white matter of the cerebellum. They had short dendrites, and some showed an
      abnormal direction of dendrites in rats exposed to 2.25 or 2.5 Gy. Alignment of
      Purkinje cells was also disturbed when examined either on P5, P7 or P9 especially
      by doses of 2.25 and 2.5 Gy. There was a relationship between X-ray doses and the
      number of cells piling up in the Purkinje cell layer of the cerebellum. The dose
      response relationship with the number of ectopic Purkinje cells was noted in the
      anterior lobes of the cerebellum.

PMID- 12212619
TI  - Sympathetic nerve response to muscle during anteroposterior acceleration in
      humans.
AB  - This study aimed to elucidate the effects of linear acceleration on muscle
      sympathetic nerve activity (MSNA) in humans. Eight healthy young male volunteers
      were seated in a linear accelerator (sled) during the recording of their
      electrocardiogram, blood pressure with the Finapres, thoracic impedance and
      respiration curve. MSNA was recorded from the tibial nerve by microneurography.
      At a fixed distance of sled movements in an anteroposterior direction, eight
      modes of stimulation with peak accelerations at 0.05, 0.10, 0.15, and 0.20 G
      (gravity) in sinusoidal or step mode were applied to each subject. Each movement
      was repeated for 5 cycles. Both the total activity and the burst rate of MSNA
      decreased during acceleration, and the level of the decrease was proportional to
      the level of the acceleration, whereas the average heart rate, thoracic impedance
      and mean arterial pressure did not change significantly. These results suggests
      that moderate linear acceleration may suppress MSNA in humans.

PMID- 12212620
TI  - Effects of lower body positive pressure on muscle sympathetic nerve activity.
AB  - To elucidate the role of vasomotor sympathetic nerve activity response to lower
      body positive pressure (LBPP), muscle sympathetic nerve activity (MSNA) along
      with blood pressure, electrocardiogram, transthoracic impedance and
      echocardiogram were recorded in ten healthy young men at 10, 20 and 30 mmHg LBPP
      in the supine position. We found that MSNA was suppressed (27%) at both 10 and 20
      mmHg LBPP but tended to increase at 30 mmHg LBPP. Mean arterial pressure (11%)
      and total peripheral resistance (36%) increased despite a tendency toward
      decreased stroke volume and cardiac output at 30 mmHg LBPP. Heart rate remained
      unchanged. The left atrial dimension significantly increased during 10-30 mmHg
      LBPP, indicating an increase in cardiac filling. These results suggest that LBPP
      at levels less than 20 mmHg suppressed MSNA by the translocation of blood from
      the lower body to the thorax, thus stimulating the cardiopulmonary baroreceptors
      which in turn inhibited vasomotor sympathetic nerve activity. However, LBPP at 30
      mmHg tended to enhance MSNA through the activation of intramuscular (pressure
      sensitive) receptors which could counteract the inhibitory effect of
      cardiopulmonary baroreflexes on MSNA.

PMID- 12212621
TI  - Elicitation of vestibular nystagmus by a step mode of horizontal linear
      acceleration.
AB  - Elicitation of lateral nystagmus to linear acceleration in the interaural axis of
      the head was examined in 35 healthy subjects who were seated upright in darkness
      within the capsule (sled) of an accelerator. The motion stimulus was a step-mode
      oscillation of 0.3 G and 0.5 G at a distance of 10 m, though an additional 0.1 G
      stimulus was given in 10 subjects. The nystagmus was already fully elicited at
      0.3 G in 13 subjects. In 9 of the remainder, however, the occurrence was newly
      developed or further improved at 0.5 G. When 10 subjects among the full
      elicitation group at 0.3 G were examined at 0.1 G, only one subject still
      maintained high susceptibility. G-direction-dependent asymmetry was frequently
      observed in the nystagmus elicitation. Such directional preponderance was
      distinct at 0.3 G, but lessened at 0.5 G, when the subjects were examined whose
      nystagmus elicitation was very frequent. The results indicate that a greater G
      load is more efficient for nystagmus elicitation, but may eliminate further
      chances to identify the response properties.

PMID- 12212622
TI  - Adolescent medicine.

PMID- 12212623
TI  - Electromyography.

PMID- 12212624
TI  - Effects of acute mild and moderate hypoxia on human mood state.
AB  - OBJECTIVE: To explore the effects of acute mild and moderate hypoxia on human
      mood state. METHOD: The mood states of 18 healthy male volunteers were evaluated
      by self-assessment questionnaires, profile of mood state (POMS) and state anxiety
      inventory (S-AI) after random exposure to simulated altitude of 300 m (control),
      2800 m, 3600 m and 4400 m for 1 h in a hypobaric chamber. RESULT: The data at 300
      m level were taken as the baseline control. The negative mood state factor points
      (tension, fatigue etc.) increased gradually as the altitude level increased while
      V (vigor-activity) points had a tendency to decrease (P<0.05 or P<0.01). No
      significant difference was found in the points of (D, A) even under exposure to
      4400 m (P>0.05). At the early period of 2800 m exposure the tension points of
      POMS and S-AI scores were higher than those of control level (P<0.05) then
      dropped to baseline level when exposure to this altitude for 1 h. CONCLUSION:
      Exposure to acute mild hypobaric hypoxia at 2800 m for 1 h has adverse effect on
      mood state of healthy person and the negative effect was further aggravated with
      the increment of altitude level.

PMID- 12212625
TI  - [Effects of repeated low body negative pressure (LBNP) exposures on LBNP
      tolerance].
AB  - OBJECTIVE: To investigate variation of low body negative pressure (LBNP)
      tolerance and the relationship with change of heart function after repeated LBNP
      exposures. METHOD: Ten healthy subjects were exposed to eight min consecutive
      daily LBNP (-50 mmHg). Before and after this exposures, tolerance to LBNP was
      determined by a cumulative stress index (CSI) and duration of negative pressure
      (DNP). RESULT: The pre- and post repeated exposure values of CSI and DNP were
      1058 +/- 216 s, 1354 +/- 233 s and 45833 +/- 12546 s mmHg, 63433 +/- 13458 s
      mmHg, respectively. It showed that both were increased significantly (P<0.05),
      and the heart function was showed to have a tendency of being enhanced.
      CONCLUSION: It suggested that LBNP tolerance increased after repeated exposures,
      which might be achieved via strengthening of ventricular contractivity,
      decreasing the compliance of peripheral vascular, the hypotensive [correction of
      hypotentive] reflex compensatory mechanisms becoming more effective, and
      increasing arterial blood pressure on heart level.

PMID- 12212626
TI  - Effect of total flavonoids of hippophae rhamnoides on contractile mechanics and
      calcium transfer in stretched myocyte.
AB  - OBJECTIVE: To study the role of total flavonoids of hippophae rhamnoides in
      improving contractile [correction of contactile] function of stretched cardiac
      myocyte. METHOD: Flavonoids were given to stretched myocytes which were proved
      their contractile function decline and then myocyte contractile mechanics
      characteristics and calcium transfer were measured. RESULT: Flavonoids increased
      myocyte contractility, as indicated by myocyte shortening, velocity of
      shortening, peak +dL/dt and peak -dL/dt during shortening, in a concentration
      dependent manner (r>0.9, P<0.001), and with no relation to the intracellular
      calcium transfer in the myocytes. CONCLUSION: Flavonoids of the traditional
      Chinese drug hippophae rhamnoides is effective in improving the contractile
      function of stretched cardiac myocyte in low dosage.

PMID- 12212628
TI  - Effect of moderate and severe heat stress on avian embryonic hsp70 gene
      expression.
AB  - Stress response is a universal mechanism developed by all organisms to deal with
      adverse changes in the environment, which lead to the synthesis of heat shock
      proteins (Hsps). In this study, the effect of moderate (41 degrees C) and severe
      (44 degrees C) heat stress on Hsp70 transcript expression pattern was
      investigated during chicken embryogenesis. Acute exposure to severe heat stress
      for one hour resulted in a fifteen-fold increase in Hsp70 mRNA levels. The return
      of stressed embryos to normal incubation temperature resulted in Hsp70 mRNA
      levels five-fold higher than control after three hours and normal levels after
      six hours. Moderate heat stress did not induce enhancements on Hsp70 mRNA levels.
      The spatial expression of Hsp70 transcripts was detected in embryos under normal
      incubation conditions. Whole-mount in situ hybridization analysis showed that
      Hsp70 transcripts were constitutively present in somite and in distinct
      encephalic domains (predominantly in prosencephalon and mesencephalon areas) of
      the chicken embryo. These results showed that Hsp70 induction is dependent on
      incubation temperature conditions, suggesting that early chicken embryos may
      induce a quick emergence response to cope with severe heat stress by increasing
      Hsp70 mRNA levels.

PMID- 12212627
TI  - Secretion of insulin-like growth factor (IGF)-I and -II and IGF binding proteins
      (IGFBPs) in fetal stromal-vascular (S-V) cell cultures obtained before and after
      the onset of adipogenesis in vivo.
AB  - The present study examined the influence of dexamethasone (DEX) treatment on
      preadipocyte differentiation and insulin-like growth factor binding protein
      (IGFBP) secretion in stromal-vascular (S-V) cell cultures established from
      subcutaneous adipose tissue obtained from nine 75 day and four 50 day pig
      fetuses. Cultures of S-V cells from four young pigs (5-7 days old) were also
      studied. Each fetal S-V cell culture represented 1 pool of S-V cells/dam.
      Cultures were seeded and plated in 10% FBS from day 0-3 and treated with insulin
      (ITS) + 10 nM DEX from day 3-6 (late DEX treatment). Alternatively, cultures were
      seeded and plated in 10% FBS + 80 nM DEX from day 0-3 and treated with insulin
      alone from day 3-6 (early DEX treatment). Conditioned media was collected on day
      6 of culture after 3 days of conditioning, and prepared for subsequent 125I-IGF-I
      ligand blot analysis for IGFBPs and RIA for IGF-I and IGF-II. Early and late DEX
      increased (P<0.05) preadipocyte (AD-3+) recruitment but only early DEX increased
      preadipocyte differentiation (lipid + and C/EBP alpha+) by day 6 in S-V cultures
      from 75 day fetuses. Levels of IGFBP-2, IGFBP-4, IGF-I and IGF-II in media
      conditioned by 75 day fetal S-V cultures were not influenced by late DEX.
      However, late DEX reduced levels of 29 kDa IGFBPs and markedly increased (P<0.05)
      IGFBP-3 levels in 75 day S-V media. Late DEX also markedly increased (P<0.05)
      IGFBP-3 levels in 50 day S-V media but had little influence on other IGFBPs.
      Early DEX treatment increased (P<0.05) IGFBP-4 levels in 75 day S-V media but had
      little to no influence on levels of IGF-I, IGF-II and other IGFBPs. These studies
      indicate that IGFBP-4 may regulate local metabolism during preadipocyte
      differentiation, whereas IGFBP-3 may antagonize preadipocyte differentiation by
      targeting IGF-I away from differentiating cells and towards growing cells.

PMID- 12212629
TI  - Myostatin and TGF-beta2 gene expression patterns in response to in ovo
      administration of rhIGF-I during chicken embryonic development.
AB  - The objective of the study was to evaluate the impact of in ovo administration of
      recombinant human insulin-like growth factor-I (rhIGF-I) on myostatin and
      transforming growth factor-beta2 (TGF-beta2) gene expression during chicken
      embryogenesis with emphasis on skeletal muscle development. Eggs were injected
      once with 100 ng rh IGF-I in 10 mM acetic acid, 0.1% BSA per embryo on day 3 of
      embryonic development. Total RNA was isolated from whole embryos on each of
      embryonic days (E) 0 to 6 (n = 6 per day/per treatment), from thoracic/abdominal
      halves of the embryo at E 7 to 8 (n = 6 per day/per treatment), and from
      pectoralis muscle tissues at E 9 to 20 (n = 4 per day/per treatment). Reverse
      transcription polymerase chain reaction (RT-PCR) was used to synthesize cDNAs.
      Myostatin mRNA isolated from pectoralis muscles of the rhIGF-I treated group
      increased on E 10 (approximately 2.5 fold) and remained high through E 13,
      whereas myostatin mRNA from control pectoralis muscles increased at E 9 and
      remained high until E 12. TGF-beta2 gene expression from in ovo rhIGF-I treated
      pectoralis muscles dramatically increased at E 13 (approximately 2.5 fold), in
      contrast to E 14 from control pectoralis muscle, and gradually declined through E
      16. Our results demonstrate that in ovo administration of rhIGF-I on E 3 may
      alter developmental expression patterns of myostatin and TGF-beta2 genes.

PMID- 12212631
TI  - Lead and the developing nervous system.
AB  - Subtle signs of neural impairment are appearing in children exposed to "low
      levels" of lead. How does this metal exert its effect on the developing nervous
      system? The salient features of five mechanisms likely involved are discussed in
      this review.

PMID- 12212632
TI  - Variability of sleep parameters across multiple laboratory sessions in healthy
      young subjects: the "very first night effect".
AB  - Many studies have been carried out to assess the variability of sleep parameters.
      The first night effect is one of the most important factors in this variability
      and has been extensively studied. However, the readaptation phenomenon when
      subjects returned to the sleep laboratory after spending a certain period of time
      at home has been not systematically evaluated. To investigate this phenomenon
      across multiple sleep laboratory sessions, polysomnographic data from 12 healthy
      young subjects for 12 nights (three periods each of 4 consecutive nights, with a
      minimum of 1 month between them) were collected. The first night effect was
      present only in the first night of the first period ("very first night") and was
      significant only for REM sleep-related variables. We conclude that the results
      from the first nights of consecutive periods within a specific protocol with
      healthy young subjects need not be discarded in subsequent analyses.

PMID- 12212630
TI  - Age-related changes in the D-aspartic acid content of the cranial bones in
      senescence-accelerated mice (SAM).
AB  - We measured the age-related changes in the D/L-aspartic acid ratio (D/L ratio) of
      cranial bones in two different sublines of senescence-accelerated mice (SAM/Iw):
      SAMP2/Iw (SAM, prone 2/Iwate) and SAMR1/Iw (SAM, resistant 1/Iwate). In SAM/Iw
      under 9 months of age, the D/L ratio in SAMP2/Iw was higher than that in SAMR1/Iw
      (p<0.001). However, in all 12-month old SAM/Iw, whether SAMP2/Iw or SAMR1/Iw, the
      D/L ratio was higher in males than in females. There were minor differences in
      the age-related changes in the D/L ratios between different types of cranial
      bone. In 1-month old SAM/Iw the rectal temperature was similar in both males and
      females. However from the age of 2 months, there was a divergence, with the
      rectal temperature measurement in SAMP2/Iw reaching a peak 2 months of age,
      whereas SAMR1/Iw had the highest temperature readings at 6 months of age. In both
      SAMP2/Iw older than 2 months, and SAMR1/Iw older than 6 months, the temperature
      readings tended to gradually decrease with age in both males and females. These
      results suggest that the differences in D/L-aspartic acid ratios were dependent
      on the age, gender, and strain of SAM/Iw, but were not dependant on the type of
      cranial bone studied. It seems likely that these differences may be related
      mainly to changes in body temperature.

PMID- 12212633
TI  - Toward a chronopsychophysiology of mental rotation.
AB  - In a parity judgment task, the ERPs at parietal electrode sites become the more
      negative the more mental rotation has to be executed. In two experiments, it was
      investigated whether a temporal relationship exists between the onset of this
      amplitude modulation and the moment when mental rotation is executed. Therefore,
      the duration of processing stages located before mental rotation was manipulated.
      The amplitude modulation was delayed when either the perceptual quality of the
      stimulus was reduced (Experiment 1) or when character discrimination was more
      difficult (Experiment 2). The results suggest that the onset of the rotation
      related negativity might be used as a chronopsychophysiological marker for the
      onset of the cognitive process of mental rotation.

PMID- 12212634
TI  - An alternative to Unibase/glycol as an effective nonhydrating electrolyte medium
      for the measurement of electrodermal activity.
AB  - Although Unibase cream has been an effective medium for electrodermal recordings,
      its production has recently been discontinued. This study compared alternative
      media to Unibase for effectiveness. Three base creams similar to Unibase were
      initially compared for in vitro viscosity and effectiveness. Based upon this
      analysis one cream was eliminated. A volunteer sample of 6 postmenopausal women
      with hot flashes and 6 young women without flashes was recruited. Media were
      evaluated for viscosity and effectiveness of skin conductance. Results indicated
      that one electrolyte media produced readings within the normal range, identified
      true positive hot flashes, and produced few false negative readings whereas the
      second produced largely unreadable results with many false negative hot flashes.
      An appropriate substitute for Unibase as an effective electrolyte medium for
      measurement of electrodermal activity was identified.

PMID- 12212635
TI  - Contribution of tonic vagal modulation of heart rate, central respiratory drive,
      respiratory depth, and respiratory frequency to respiratory sinus arrhythmia
      during mental stress and physical exercise.
AB  - This study tested various sources of changes in respiratory sinus arrhythmia
      (RSA). Twenty-two healthy participants participated in three experimental
      conditions (mental stress, relaxation, and mild physical exercise) that each
      consisted of three breathing parts (normal breathing, breathing compressed room
      air, and breathing compressed 5% CO2-enriched air). Independent contributions to
      changes in RSA were found for changes in tonic vagal modulation of heart rate,
      central respiratory drive (i.e., PaCO2), respiratory depth, and respiratory
      frequency. The relative contributions to changes in RSA differed for mental
      stress and physical exercise. It is concluded that uncorrected RSA will suffice
      to index within-subject changes in tonic vagal modulation of heart rate in most
      situations. However, if the central respiratory drive is expected to change, RSA
      should ideally be corrected for changes in PaCO2, respiratory depth, and
      respiratory frequency.

PMID- 12212636
TI  - Crossmodal links in spatial attention are mediated by supramodal control
      processes: evidence from event-related potentials.
AB  - Crossmodal links in spatial attention were studied in an experiment where
      participants had to detect peripheral tactile or visual targets on the attended
      side, while ignoring all stimuli on the unattended side and in the currently
      irrelevant modality. Both relevant locations and relevant modalities were
      specified on a trial-by-trial basis by auditory precues. Spatial orienting in the
      cue-target interval was reflected in anterior negativities and occipital
      positivities contralateral to the cued side, either when vision or touch was cued
      as relevant. These effects resembled previously reported ERP modulations during
      shifts of visual attention, implicating supramodal mechanisms in the control of
      spatial attention and demonstrating their independence of cue modality. Early
      effects of spatial attention on somatosensory and visual ERPs were of equivalent
      size for currently relevant and irrelevant modalities. Results support the idea
      that crossmodal links in spatial attention are mediated by supramodal control
      mechanisms.

PMID- 12212637
TI  - Power changes in infant EEG frequency bands during a spatial working memory task.
AB  - Developmental psychophysiologists working with infants have no commonly accepted
      frequency definitions of EEG waves or rhythms. The purpose of this study was to
      investigate the task-related power changes in three infant EEG frequency bands
      during the performance of a spatial working memory task by 8-month-old infants.
      EEG data were divided into three frequency bands: 3-5 Hz, 6-9 Hz, and 10-12 Hz.
      Although all three frequency bands showed some level of discrimination of
      baseline from task and among different processing stages of cognitive activity,
      only the 6-9 Hz band consistently exhibited these capabilities and distinguished
      the correct from incorrect responses. These data may form the foundation for
      defining EEG frequency bands that are appropriate for use with infant research
      participants and for understanding the function of these frequencies during
      cognitive activity.

PMID- 12212639
TI  - Exaggeration of blood pressure-related hypoalgesia and reduction of blood
      pressure with low frequency transcutaneous electrical nerve stimulation.
AB  - Reduced pain perception has been observed in hypertensive individuals and
      normotensive individuals at risk for high blood pressure and may involve
      increased endogenous opioid release or receptor sensitivity. The present study
      examined the issue by administering two subjectively similar but physiologically
      different forms of the pain-reducing procedure transcutaneous electrical nerve
      stimulation (TENS). Men varying in resting blood pressure and parental history of
      hypertension participated in three testing sessions during which was presented
      (a) high-frequency (100 Hz) TENS; (b) low-frequency (2 Hz) TENS, the type
      believed to elicit endogenous opioid activity; or (c) no-TENS stimulation.
      Measurements of blood pressure (BP) and other physiological variables were
      obtained during this period. Afterwards, two pain stimuli were presented: a
      series of electric shocks and 5 min of arm ischemia. There was a significant
      negative association between pain and resting systolic blood pressure (SBP), and
      pain and parental history of hypertension in the no-TENS and high-frequency TENS
      conditions that was significantly strengthened by administration of low-frequency
      TENS. As well, low-frequency TENS produced a modest but significant acute
      reduction in SBP, especially among those with higher resting levels. These
      results provide further evidence that opioid mechanisms are involved in blood
      pressure-related hypoalgesia and blood pressure regulation.

PMID- 12212638
TI  - Brain mechanisms of visual encoding and working memory in psychometrically
      identified schizotypal individuals and after acute administration of haloperidol.
AB  - A probabilistic association task that manipulated the necessity to temporarily
      store information was combined with the recording of event-related potentials. In
      Experiment 1, scores obtained from a positive schizotypy scale were used to
      categorize participants as either low or high schizotypal individuals. Low, but
      not high, schizotypal individuals displayed evidence for selective associative
      learning in the working memory dependent ("trace") version of the task. The
      amplitudes of the occipito-temporal N150 were attenuated in high schizotypal
      individuals. In Experiment 2, the intravenous administration of a single dose of
      haloperidol (0.04 mg/kg), but not of a placebo, strengthened the selectivity of
      associative learning in the trace version of the task. The amplitudes of the
      occipito-temporal N150 were augmented by haloperidol. Psychometrically identified
      schizotypal individuals and normal individuals under mild stress demonstrated
      defective prioritization of information in working memory and deficient visual
      encoding. These neurocognitive effects of schizotypy and stress seem to be
      mediated by the D2 family of dopamine receptors.

PMID- 12212640
TI  - Visual categorization during childhood: an ERP study.
AB  - Categorization is a basic means of organizing the world around us and offers a
      simple way to process the mass of stimuli one perceives every day. The ability to
      categorize appears early in infancy, and has important ramifications for the
      acquisition of other cognitive capacities, but little is known of its development
      during childhood. We studied 48 children (7-15 years of age) and 14 adults using
      an animal/nonanimal visual categorization task while event-related potentials
      (ERPs) were recorded. Three components were measured: P1, N2, and P3.
      Behaviorally, the children performed the task very similarly to adults, although
      the children took longer to make categorization responses. Decreases in latencies
      (N2, P3) and amplitudes (P1, N2, P3) with age indicated that categorization
      processes continue to develop through childhood. P1 latency did not differ
      between the age groups. N2 latency, which is associated with stimulus
      categorization, reached adult levels at 9 years and P3 latency at 11 years of
      age. Age-related amplitude decreases started after the maturational changes in
      latencies were finished.

PMID- 12212641
TI  - Reduction in serum cortisol after platinum based chemotherapy for cancer: a role
      for the HPA axis in treatment-related nausea?
AB  - Many adverse effects commonly associated with chemotherapy, such as nausea,
      vomiting, and fatigue, are also characteristic of adrenal insufficiency. It is
      conceivable that chemotherapy drugs may directly or indirectly impact the
      activity of the hypothalamic-pituitary-adrenal axis. We examined this conjecture
      by characterizing temporal changes in blood cortisol concentrations in women with
      ovarian carcinoma given chemotherapy. Twenty-three chemotherapy-naive women with
      histologically confirmed ovarian cancer underwent serial blood sampling for
      determination of cortisol levels prior to and every hour for 6 hr following two
      chemotherapy treatments with cisplatin or carboplatin. Samples were also taken
      for 4 hr on a comparison day when all study procedures were performed except
      chemotherapy administration. A significant reduction in serum cortisol was found
      immediately following infusion of either cisplatin or carboplatin. No progressive
      reduction in cortisol was found over the two treatment cycles. Because the
      reduction in cortisol was seen only in the presence of the cytotoxic drug, it is
      likely that the effect of the drug is "direct" and does not involve overt
      psychological or circadian mechanisms. The possible role of this reduction in
      cortisol is discussed in relation to induction of chemotherapy-induced nausea and
      vomiting.

PMID- 12212642
TI  - Influence of preparatory schema on the speed of responses to spatially compatible
      and incompatible stimuli.
AB  - We investigated the inhibitory regulation of perceptual-motor processing streams
      in a task that switched between spatially compatible and incompatible stimulus
      response mappings. Thirty male and female college-aged participants performed a
      reaction time (RT) task in which the response was either spatially compatible or
      not depending on a cue immediately preceding the stimulus. The cue-to-stimulus
      interval (CI) was either 50 or 500 ms. Incompatible mapping yielded the typical
      slower responses than compatible mapping at 500 ms, but not at 50 ms. Changes in
      cardiac interbeat interval (IBI) and performance suggested that automatic
      responses to compatible stimuli were suppressed at 50 ms. Both performance and
      IBI changes as well as individual differences in these measures suggested a
      precue preparatory schema or set biased toward suppressing the compatible
      mapping. An alternate hypothesis of a cue-induced suppression was questioned. The
      results illustrate the operation of different supervisory processes in the
      anticipatory and online control of action.

PMID- 12212643
TI  - Aversive Pavlovian conditioning in psychopaths: peripheral and central
      correlates.
AB  - Differential aversive Pavlovian conditioning with a foul odor as unconditioned
      stimulus (US) and neutral faces as conditioned stimuli (CS) was compared between
      9 noncriminal psychopaths as defined by the Hare Psychopathy Checklist Revised
      and 12 healthy controls. Event-related potentials (ERP), heart rate, skin
      conductance response, corrugator EMG, and startle response potentiation as well
      as valence, arousal, and contingency of the CS were assessed. Whereas the healthy
      controls (HC) showed significant CS +/CS- differentiation, the psychopaths (PP)
      failed to exhibit a conditioned response although unconditioned responses were
      comparable between the groups. N100, P200, and P300 to the CSs revealed that
      psychopaths were not deficient in information processing and showed even better
      anticipatory responding than the HC group indicated by the terminal contingent
      negative variation (tCNV), that lacked, however, CS+ and CS- differentiation.
      These data indicate a deficit in association formation in psychopaths that may be
      related to deficient interaction of limbic-subcortical and cortical structures.

PMID- 12212644
TI  - Affective imagery and the startle response: probing mechanisms of modulation
      during pleasant scenes, personal experiences, and discrete negative emotions.
AB  - Two experiments addressed the following issues concerning modulation of the
      acoustic startle reflex during emotional imagery: (1) Is startle inhibited or
      potentiated during imagery of pleasurable events? (2) Does startle modulation
      differ for personal versus standard imagery scenes? (3) Is startle modulated
      differently during anger versus fear? For standard scenes, startle was greater
      during aversive than pleasant imagery, with both exceeding neutral. Blink
      potentiation was greater during imagery of personal pleasant than nonpersonal
      pleasant scenes. Startle potentiation did not differ for anger versus fear
      material, but differences were found in self-report, corrugator EMG, and HR
      response. These results suggest that in addition to the emotional valence of
      imagined material, startle reactivity is influenced by the degree of engagement
      or active disengagement from the sensory environment. The findings also indicate
      that fear and anger are differentiable in terms of affective report, cardiac
      mobilization, and expressive behavior, but not at the primary motivational level
      at which reflex priming occurs.

PMID- 12212645
TI  - Temporary and longer term retention of acoustic information.
AB  - Though many studies suggest that fine acoustic details fade from memory after 15
      s or even less, everyday experience tells us that the voice of a person or a
      musical instrument can be recognized long after it was last heard. We wished to
      determine whether tones leave a lasting memory trace using an experimental model
      of implicit recognition and testing whether exact pitch information can be
      retrieved even after 30 s. Event-related brain potentials demonstrated the
      survival of an accurate representation of tone pitch in the auditory cortex. This
      result provides a link between short-duration buffering and permanent storage of
      acoustic information.

PMID- 12212646
TI  - The role of psychophysiology in clinical assessment: ERPs in the evaluation of
      memory.
AB  - Psychophysiological measures hold great potential for informing clinical
      assessments. The challenge, before such measures can be widely used, is to
      develop test procedures and analysis strategies that allow for statistically
      reliable and valid decisions to be made for any particular examinee, despite
      large individual differences in psychophysiological responding. Focusing on the
      evaluation of memory in clinical, criminal, and experimental contexts, this paper
      reviews the rationale for and development of ERP-based memory assessment
      procedures, with a focus on methods that allow for statistically supported
      decisions to be made in the case of a single examinee. The application of one
      such procedure to the study of amnesia in Dissociative Identity Disorder is
      highlighted. To facilitate the development of other psychophysiological
      assessment tools, psychophysiological researchers are encouraged to report the
      sensitivity and specificity of their measures where possible.

PMID- 12212647
TI  - Emotion regulation: affective, cognitive, and social consequences.
AB  - One of life's great challenges is successfully regulating emotions. Do some
      emotion regulation strategies have more to recommend them than others? According
      to Gross's (1998, Review of General Psychology, 2, 271-299) process model of
      emotion regulation, strategies that act early in the emotion-generative process
      should have a different profile of consequences than strategies that act later
      on. This review focuses on two commonly used strategies for down-regulating
      emotion. The first, reappraisal, comes early in the emotion-generative process.
      It consists of changing the way a situation is construed so as to decrease its
      emotional impact. The second, suppression, comes later in the emotion-generative
      process. It consists of inhibiting the outward signs of inner feelings.
      Experimental and individual-difference studies find reappraisal is often more
      effective than suppression. Reappraisal decreases emotion experience and
      behavioral expression, and has no impact on memory. By contrast, suppression
      decreases behavioral expression, but fails to decrease emotion experience, and
      actually impairs memory. Suppression also increases physiological responding for
      suppressors and their social partners. This review concludes with a consideration
      of five important directions for future research on emotion regulation processes.

PMID- 12212648
TI  - Cardiovascular patterns associated with threat and challenge appraisals: a within
      subjects analysis.
AB  - Previous studies demonstrated distinct cardiovascular patterns associated with
      threat and challenge appraisals for groups of participants. We extend these
      results by assessing whether appraisals continue to be associated with these
      cardiovascular response patterns within an individual as appraisals change.
      Participants completed four verbal mental arithmetic tasks for which they made
      appraisals before and after each task. Cardiac reactivity and total peripheral
      resistance (TPR) were calculated for the first and last minutes of each task, and
      the number of responses and percent correct were measured for each task. In line
      with our prediction, pretask appraisals were related to some task-related cardiac
      responses across the four tasks. In addition, task-related cardiovascular
      reactivity and behaviors both influenced appraisals following the task. Our
      findings suggest that an idiographic analysis of appraisals, cardiovascular
      physiology, and task-related behaviors provides a richer understanding of the
      appraisal process and reveals sex differences deserving further assessment.

PMID- 12212649
TI  - The relationship of age and cardiovascular fitness to cognitive and motor
      processes.
AB  - Older and younger aerobically trained and sedentary adults participated in an S1
      S2-S3 paradigm designed to elicit event-related potential (ERP) and behavioral
      responses to determine the influence of cardiovascular fitness on cognitive and
      motor processes. The paradigm provided warning (S1) as to the difficulty level of
      an upcoming decision task (S2). Participants had to decide the taller of two bars
      on presentation of S2 but hold their response until S3, to which they indicated
      their choice motorically. Results revealed age-related differences for ERP
      measures as older participants showed increased amplitude of the stimulus
      preceding negativity (SPN) prior to S2, and longer latencies and equipotentiality
      of P3 in response to S2. Fitness effects were also observed for the contingent
      negative variation (CNV) with decreased amplitude for fit relative to sedentary
      individuals. Age interacted with fitness for P3 latency to S2 as older sedentary
      individuals showed the longest latency followed by older fit and both younger
      groups. No significant group differences were observed for reaction time (RT) to
      S3. Therefore, physical fitness is associated with attenuation of cognitive
      decline in older individuals and greater economy of motor preparation for both
      young and older participants.

PMID- 12212650
TI  - Driver fatigue: electroencephalography and psychological assessment.
AB  - Fatigue has major implications for transportation system safety; therefore,
      investigating the psychophysiological links to fatigue could enhance our
      understanding and management of fatigue in the transport industry. This study
      examined the psychophysiological changes that occurred during a driver simulator
      task in 35 randomly selected subjects. Results showed that significant
      electroencephalographic changes occur during fatigue. Delta and theta activity
      were found to increase significantly during fatigue. Heart rate was significantly
      lower after the driving task. Blink rate also changed during the fatigue task.
      Increased trait anxiety, tension-anxiety, fatigue-inertia and reduced vigor
      activity were shown to be associated with neurophysiological indicators of
      fatigue such as increased delta and theta activity. The results are discussed in
      light of directions for future studies and for the development of a fatigue
      countermeasure device.

PMID- 12212651
TI  - Psychophysiological correlates of narcissistic traits in women during active
      coping.
AB  - Two dimensions of narcissism were related to psychophysiological responses to
      stress in 50 young women. Cardiovascular, electrodermal, task performance, and
      stress appraisal measures were recorded during rest, mental arithmetic, and a
      computerized Thematic Apperception Test (Murray, 1943). The Egocentricity and
      Alienation scales of the Bell Object Relations and Reality Testing Inventory
      (Bell, 1995) served as measures of overt/inflated and covert/deflated narcissism.
      Egocentricity correlated consistently with heightened preejection period
      reactivity, whereas Alienation correlated consistently with diminished
      electrodermal reactivity (all p < .05). Multivariate analyses supported specific
      relationships between Egocentricity and preejection period hyperreactivity, and
      between Alienation and electrodermal hyporeactivity. These results have
      implications for narcissism, cardiovascular disease risk, and a variety of
      psychiatric disorders.

PMID- 12212652
TI  - Attentional modification of short-lead prepulse inhibition and long-lead prepulse
      facilitation of acoustic startle among preadolescent boys.
AB  - In adults, short-lead prepulse inhibition and long-lead prepulse facilitation of
      startle are greater during attended than ignored prestimuli. To examine these
      phenomena in children, fourteen 9- to 12-year-old boys completed a tone
      discrimination task in two sessions separated by 1 week. During each tone series,
      participants attended to one pitch and ignored the other. Startle probes (102 dB)
      were presented 120, 240, 2,000 or 4,500 ms following the onset of two-thirds of
      tones, and during one-third of intertrial intervals. Eyeblink EMG startle was
      recorded. Percent prepulse inhibition at 120 ms was greater for attended than
      ignored stimuli in Session 1 but not Session 2. Long-lead prepulse facilitation
      was marginally greater for attended than ignored tones and did not vary across
      sessions. Test-retest reliability was moderate during attended prestimuli but was
      modest during ignored prestimuli. Reliability of attentional modification was
      poorest at 120 ms and strongest at 4,500 ms. Overall, this study extended prior
      work in adults and provided a basis for further study of controlled attentional
      modification of startle in children.

PMID- 12212653
TI  - Hostility and anger expression in African American and European American men is
      associated with cardiovascular and lipid reactivity.
AB  - Physiological stress reactivity has been examined with respect to cynical
      hostility and anger expression, but primarily among Caucasians. Investigations of
      African Americans are far fewer and have focused only on the cardiovascular
      system. This study compared the relationships between hostility and anger
      expression on the one hand, and both cardiovascular and lipid reactivity on the
      other, among African Americans and European Americans. Forty-six men participated
      in a study examining cardiovascular and lipid reactivity to a speech stressor.
      African American men low in cynical hostility had greater blood pressure
      reactivity to the stressor; this effect appeared to be due primarily to low
      cynical men with high Anger In. Independent of ethnicity, those with a general
      tendency to either always express or always inhibit the expression of anger had
      higher triglyceride reactivity, relative to those with a more flexible style of
      anger expression. These results suggest that it is important to examine ethnicity
      in relationship to measures of hostility and anger expression, to uncover
      vulnerable individuals.

PMID- 12212654
TI  - Covariations of EEG asymmetries and emotional states indicate that activity at
      frontopolar locations is particularly affected by state factors.
AB  - To test the hypothesis that activation asymmetries of the most anterior parts of
      the prefrontal cortex may be related to state-dependent regulation of emotion,
      spontaneous changes of cortical activation asymmetries from one session to a
      second one were related to spontaneous mood changes in two large samples (ns = 56
      and 128). The interval between sessions was 2 to 4 weeks. Results show that mood
      changes specifically covary with changes of EEG asymmetry at the frontopolar
      electrode positions, but not with changes at other locations (dorsolateral
      frontal, temporal, and parietal). Anxiety, tension, and depression were found to
      decrease when frontopolar activation asymmetry shifted to the right. Taking the
      new findings into account may contribute to the refinement and extension of
      theories on EEG laterality and emotion.

PMID- 12212655
TI  - Cortisol and cardiovascular reactions to mental stress and antibody status
      following hepatitis B vaccination: a preliminary study.
AB  - This study examined possible neuroendocrine mechanisms underlying the association
      between stress and antibody response to vaccination. Hepatitis B antibody titers
      were obtained, and salivary cortisol and cardiovascular activity measured during
      baseline, mental arithmetic, and recovery in 30 undergraduates. It was
      hypothesised that higher reactivity would be associated with poorer antibody
      status. Compared to individuals with high antibody titers, those with low titers
      had significantly lower cortisol levels throughout, exhibited a significantly
      attenuated end-of-task reduction in cortisol relative to resting baseline, and
      had larger cardiac output and inotropic reactions, but smaller increases in total
      peripheral resistance, to mental arithmetic. In sum, variations in indices of
      both hypothalamic pituitary adrenocortical axis and sympathetic nervous system
      activity were associated with individual differences in immune response to
      vaccination.

PMID- 12212656
TI  - Pain-evoked anterior cingulate activity generating the negative difference
      potential may reflect response selection processes.
AB  - The effects of a heterotopic cold pain stimulus applied to the hand on the scalp
      recorded negative difference potential (NDP) and subjective pain ratings elicited
      by electrical stimulation of the sural nerve were examined in 24 participants.
      Our previous work strongly suggests that the NDP is generated in part by the
      cognitive division of the anterior cingulate cortex (ACCcd). The latency and
      magnitude of the ACCcd activity were estimated from the NDP and from the dipole
      source localization analysis of the NDP. As expected, the sural nerve pain
      ratings were smaller in the cold pain condition than in the control condition.
      The ACCcd activity underlying the 125-ms peak of the NDP did not change across
      conditions, whereas the ACCcd activity underlying the 210-ms NDP peak was largest
      in the cold pain condition. The dissociation between pain-evoked ACCcd activity
      and pain ratings observed here and elsewhere suggest that not all of the
      nociresponsive neurons in the ACCcd are involved in pain sensation. Rather,
      differences in the cognitive demands of the control and cold pain conditions
      suggest that the pain-evoked 210-ms ACCcd activity reflects response selection
      processes, perhaps response competition monitoring.

PMID- 12212657
TI  - Are rules applied in Pavlovian electrodermal conditioning with humans general or
      outcome specific?
AB  - There is growing evidence that in human skin conductance response (SCR)
      conditioning positive patterning (A-, B-, AB+) and negative pattering (A+, B+, AB
      ) are solved by applying two different rules. The present experiments
      investigated whether the representations of such rules are specific or general
      with regard to outcomes and response systems. In Experiment 1, we investigated
      SCR and eyelid conditioning with different types of training administered in an
      interleaved fashion. We found that positive patterning SCR conditioning
      interfered with negative patterning SCR conditioning, whereas eyeblink
      conditioning had no effect on SCR conditioning. In Experiment 2, in which
      eyeblink and SCR conditioning were administered in sequential fashion, the same
      result was obtained. We conclude that the rules involved in solving patterning
      tasks might be specific to outcomes and/or response systems.

PMID- 12212658
TI  - P300 amplitude is determined by target-to-target interval.
AB  - P300 event-related brain potential (ERP) measures are affected by target stimulus
      probability, the number of nontargets preceding the target in the stimulus
      sequence structure, and interstimulus interval (ISI). Each of these factors
      contributes to the target-to-target interval (TTI), which also has been found to
      affect P300. The present study employed a variant of the oddball paradigm and
      manipulated the number of preceding nontarget stimuli (0, 1, 2, 3) and ISI (1, 2,
      4 s) in order to systematically assess TTI effects on P300 values from auditory
      and visual stimuli. Number of preceding nontargets generally produced stronger
      effects than ISI in a manner suggesting that TTI determined P300 measures:
      Amplitude increased as TTI increased for both auditory and visual stimulus
      conditions, whereas latency tended to decrease with increased TTI. The finding
      that TTI is a critical determinant of P300 responsivity is discussed within a
      resource allocation theoretical framework.

PMID- 12212659
TI  - Difficulty does not account for emotion-specific heart rate changes in the
      directed facial action task.
AB  - Boiten (1996) used the Directed Facial Action task (a task we developed in which
      participants follow instructions, based on theory about how emotion is expressed
      in the face, to move facial muscles deliberately to produce different facial
      configurations) to investigate heart rate differences among six emotional
      configurations. Boiten's findings closely replicated ours (Levenson, Ekman, &
      Friesen, 1990) in terms of heart rate change, self-reported emotion, and rated
      difficulty during the configurations. Boiten concluded that differences in
      difficulty were responsible for found differences in heart rate; in contrast, we
      had concluded that heart rate findings could not be explained in this manner. In
      this paper, we argue that neither Boiten nor we did the critical analyses needed
      to determine whether heart rate changes were mediated in this way. Performing
      these analyses, we conclude that neither reported difficulty nor two other
      potential mediators (time required to make the facial configurations; activity of
      nonfacial muscles) mediated the heart rate differences that we found between
      emotional configurations in the Directed Facial Action task.

PMID- 12212660
TI  - Atypical autonomic regulation in perpetrators of violent domestic abuse.
AB  - Perpetrators of domestic violence describe symptoms that are compatible with
      exaggerated autonomic arousal at the time of the domestic violence. This
      inappropriate arousal may be reflected in altered heart rate regulation. If heart
      rate is systematically regulated by vagal mechanisms, then increases in heart
      rate should correlate with decreases in cardiac vagal activity, as indexed by
      respiratory sinus arrhythmia (RSA). We hypothesized that perpetrators of domestic
      violence have an alteration in heart rate regulation. To test this hypothesis we
      compared the results of a postural shift performed on perpetrators, healthy
      volunteers, and nonviolent alcoholics. Results showed there were no significant
      differences in heart rate, RSA, or catecholamines. However, the significant
      inverse relationship between posture-elicited changes in RSA and heart rate
      present in the healthy volunteers was not found in perpetrators. These
      differences in the covariation between heart rate and RSA may represent
      differences in the neural regulation of heart rate and may be related to
      difficulties in controlling autonomic state.

PMID- 12212661
TI  - The temporal stability of electrodermal variables over a one-year period in
      patients with recent-onset schizophrenia and in normal subjects.
AB  - Test-retest stability of electrodermal (EDA) variables indexing both general
      autonomic arousal (e.g., skin conductance level, number of nonspecific skin
      conductance responses) and attention to external stimuli (e.g., number of skin
      conductance orienting responses, electrodermal responder/nonresponder status) was
      assessed in 71 young, recent-onset schizophrenia patients and 36 demographically
      matched normal subjects. Significant stability over a 1-year period was found for
      both patients and normal subjects for most EDA variables and for
      responder/nonresponder status, with test-retest correlations generally being
      higher for normal subjects. The lower reliability for patients was not
      attributable to symptomatic fluctuations during the follow-up period and may
      reflect poorer arousal regulation among the patients. Among measures of
      responding to nontask stimuli, a simple count of the number of orienting
      responses occurring was more stable than was a traditional trials-to-habituation
      measure.

PMID- 12212662
TI  - The impact of semantic memory organization and sentence context information on
      spoken language processing by younger and older adults: an ERP study.
AB  - To examine changes in semantic memory organization and use during aging, we
      recorded event-related potentials as younger and older adults listened to
      sentences ending with the expected word, an unexpected word from the same
      semantic category, or an unexpected word from a different category. Half of the
      contexts were highly constraining. In both groups, expected words elicited less
      negativity 300-500 ms (N400) than unexpected ones, and unexpected words elicited
      smaller N400s when these were categorically related. Whereas younger adults
      showed the greatest N400 reduction to unexpected but related words in high
      constraint contexts, older adults showed the opposite tendency. Thus, unlike
      younger adults, older adults as a group do not seem to be using context
      predictively. Older adults with higher verbal fluency and larger vocabularies,
      however, showed the younger response pattern, suggesting resource availability
      may offset certain age-related changes.

PMID- 12212663
TI  - Alpha2-noradrenergic effects on ERP and behavioral indices of auditory
      information processing.
AB  - Norepinephrine is believed to modulate CNS processing of environmental signals.
      However, its specific role in stimulus evaluation processes has not been
      delineated. We examined the effects of the alpha2 noradrenergic agents, clonidine
      and yohimbine, on ERP and performance measures of auditory information
      processing. Ten healthy participants performed a three-tone target detection
      experiment, receiving either placebo, 0.2 mg clonidine, or 30 mg yohimbine, in a
      double-blind randomized design. The principal locus of action of the
      noradrenergic agents occurred between 100 and 200 ms poststimulus. P200 latency
      was sped by yohimbine and slowed by clonidine, and the frontal P3a was shifted in
      tandem. Components related to target detection (N250 and P3b) were unaffected.
      The results suggest that norepinephrine modulates CNS mechanisms of selective
      attention to infrequent stimuli. This may be relevant for patients with
      schizophrenia, a subset of whom exhibit selective abnormalities of these same ERP
      components. Our results offer a possible link between these two sets of findings,
      suggesting that some patients with schizophrenia may have dysfunctional
      noradrenergic systems.

PMID- 12212664
TI  - Memory reactivation or reinstatement and the mismatch negativity.
AB  - Previous studies have suggested that the memory underlying the mismatch
      negativity (MMN) can be deactivated by a period of silence and later reactivated.
      An alternative is that the memory becomes inapplicable due to a period of silence
      and subsequently reinstated. Both interpretations rest on the absence of a MMN
      for a deviant in Position 1 of a train (showing deactivation or inapplicability
      of the memory) and the presence of a MMN in Position 2 of the train (evidencing
      reactivation or reinstatement of the memory). In these studies, the standards
      were fixed across all trains of a given condition. Hence, it is not clear if the
      MMN elicited in Position 2 requires presentation of multiple trains with
      identical standards or only a single train. Experiment 1 showed that a single
      train is sufficient. With data from recent studies, Experiment 2 showed that MMNs
      in Position 2 of trains are due to reinstatement rather than reactivation of the
      memory.

PMID- 12212665
TI  - Reduced sensory anticipation in migraine.
AB  - We examined differences between migraine patients and matched healthy controls in
      anticipatory processes preceding a warning stimulus and preceding a response
      stimulus during a forewarned choice reaction time task. We manipulated stimulus
      preceding negativity (SPN) by inserting full response information either at the
      instant of the warning stimulus (cue) or at the instant of the response stimulus.
      In contrast to control subjects, migraineurs with aura show low anticipation
      towards an informative cue and high anticipation towards a noninformative cue.
      Migraineurs without aura showed a cortical hypoactivation during motor
      preparation prior to the response stimulus. We propose a functional deficiency
      within frontal structures or the anterior cingulate cortex in migraine. This
      might explain the reduced anticipation, as well as the slow responses during
      selective attention that we previously reported in these patients.

PMID- 12212666
TI  - Value of event-related P300 subcomponents in the clinical diagnosis of mild
      cognitive impairment and Alzheimer's Disease.
AB  - Accurate and early diagnosis of Alzheimer's Disease (AD) with reliable and
      noninvasive methods is of great importance for clinical practice as effective and
      specific antidementive therapies become available. The aim of the study was to
      evaluate the clinical relevance of event-related P300 in the early diagnosis of
      AD. Thirty patients with AD, 26 patients with mild cognitive impairment (MCI)
      from our Memory Clinic and 26 age-matched healthy controls (HC) were studied with
      event-related P300 potentials. Amplitudes of temporo-basal dipoles (TB-P300) were
      significantly diminished in AD compared to HC and MCI. Furthermore, latencies of
      temporo-superior dipoles (TS-P300) were significantly prolonged in AD compared
      with HC. Sensitivity was 90.0% for the differentiation of patients with AD from
      HC (specificity 79.1%) using reduced TB-P300 amplitudes and prolonged TS-P300
      latencies. Similar results were found using Pz amplitudes as well as Fz
      latencies. Our data suggest that TB-P300 amplitudes and TS-P300 latencies may be
      an accurate clinically available, nonexpensive, noninvasive, and reliable marker
      for AD.

PMID- 12212667
TI  - Energy resource depletion, ability perception, and cardiovascular response to
      behavioral challenge.
AB  - This study examined cardiovascular effects of energy resource depletion.
      Participants first made a series of easy or difficult grips with their right or
      left hand. They then made and held a moderately difficult dynamometer grip with
      their right hand while measures of blood pressure and heart rate were taken. As
      expected, systolic blood pressure responses during the second task period were
      greater when the first task was difficult than when it was easy if the first task
      was performed with the right hand, but not if the first task was performed with
      the left hand. The data support the view that ability perception and, thus,
      cardiovascular responsiveness vary with relevant energy stores.

PMID- 12212668
TI  - Cardiovascular incentive effects where a challenge is unfixed: demonstrations
      involving social evaluation, evaluator status, and monetary reward.
AB  - Cardiovascular effects of social evaluation, evaluator status, and monetary
      reward were examined in participants presented with a challenge that allowed them
      to work as hard as they pleased (unfixed conditions) or called for a low level of
      effort (fixed conditions). In Experiment 1, evaluation was found to potentiate
      systolic pressure and heart rate responses insofar as the evaluator had status
      where the challenge was unfixed, but to have no impact on the responses where the
      challenge was fixed. In Experiment 2, reward value was found to potentiate the
      responses where the challenge was unfixed, but not where it was fixed. The main
      findings confirm and extend results from a previous experiment, and broaden the
      base of empirical support for the suggestion that active coping will be
      proportional to success importance where performance is unconstrained.

PMID- 12212669
TI  - Error negativity and response control.
AB  - Error trials are associated with faster responses than correct trials in simple
      discrimination tasks suggesting that errors result from impulsive responding. We
      investigated the relationship between error negativity (Ne/ERN), an event-related
      potential associated with error detection, and two behavioral indices of response
      control: response time (RT) differences between incorrect and correct trials (an
      index of impulsivity) and percentage of errors. Response-locked ERPs were
      collected from 17 young adults during a visual flanker task. Consistent with
      previous findings, participants were significantly faster on error trials.
      However, participants who exhibited larger Ne/ERN peak amplitudes had
      significantly smaller RT differences, suggesting a more controlled response
      strategy. Furthermore, Ne/ERN latencies were positively associated with
      percentage of errors. These findings are consistent with the view that the Ne/ERN
      reflects the activity of a monitoring system that is closely linked to remedial
      systems responsible for individual differences in response control or impulsive
      behavior.

PMID- 12212670
TI  - A transcranial magnetic stimulation study of information processing in the motor
      cortex: relationship between the silent period and the reaction time delay.
AB  - The present study was aimed at deciphering whether the delay in choice reaction
      time (RT) and the silent period (SP) caused by transcranial magnetic stimulation
      (TMS) of the motor cortex in the ongoing electromyogram are due to the same
      physiological mechanism. To this end, the effect of TMS was studied in 6 healthy
      volunteers performing a between-hand choice RT task. Specific predictions were
      derived from a logic inspired from the "postponed stages" hypothesis (Pashler &
      Johnson, 1989). This logic predicts a correlation between SP duration and RT when
      the stimulated cortex is involved in the response, and a stronger correlation
      when the stimulation is delivered later during the RT interval. The effect of TMS
      on RT was twofold: At early stimulation times, the stimulation shortened the RT
      and this effect was independent of the involvement of the stimulated motor cortex
      in the subsequent response. At later stimulation times, TMS had a disruptive
      effect, provided that the stimulated cortex was involved in the response. When
      the stimulated cortex was involved in the response, there was a correlation
      between SP and RT; this correlation was stronger when the stimulation occurred
      later. In contrast, there was no correlation between these two variables when the
      stimulated cortex was not involved.

PMID- 12212671
TI  - Electrical shocks to the arm elicit and inhibit startle eyeblinks.
AB  - The present study evaluated the ability of a weak electrical prepulse to modify
      startle caused by a more intense shock. Painful electrical shocks (150 V, 0.5 ms
      duration) were presented to the upper arm of college student participants,
      preceded on some trials by a weaker shock (0.5 ms duration, at perceptual
      threshold) at the same location. Intense shocks elicited eyeblink reflexes, and
      these eyeblinks were inhibited by weak electrical prepulses. These data suggest
      that the inclusion of prepulses immediately preceding painful therapeutic shocks,
      such as those generated by an implanted cardioverter-defibrillator, might be
      capable of reducing the startle response generated by that therapeutic shock.

PMID- 12212672
TI  - Cellular and mucosal immune reactions to mental and cold stress: associations
      with gender and cardiovascular reactivity.
AB  - To examine gender differences in immune reactions to stress and relationships
      between immune and cardiovascular reactivity, measures of cellular and mucosal
      immunity and cardiovascular activity were recorded in 77 men and 78 women at rest
      and in response to active (mental arithmetic) and passive (cold pressor) stress
      tasks. Both tasks reduced CD4+ T cells and the CD4/8 ratio. Total lymphocytes, NK
      cells, CD8+ T cells, and secretory immunoglobulin A (sIgA) increased with active
      stress. Passive stress decreased sIgA. At rest, men had more NK cells, less CD4+
      T cells, and fewer neutrophils than women. Mental stress increased sIgA in men
      but not women. Cardiovascular reactivity to active stress was associated with
      increases in NK cells. The data support the hypothesis that stress-related
      increases in lymphocytes are beta-adrenergically mediated, and suggest that the
      fall in CD4+ T cells may be alpha-adrenergically driven. Mechanisms underlying
      sIgA reactions are more difficult to determine. Men and women differed in some
      cell counts, but not in reactivity, although gender influenced sIgA reactions to
      arithmetic.

PMID- 12212673
TI  - Omission evoked potentials (OEPs) in rats and the effects of diazepam.
AB  - We investigated whether evoked potentials to omitted stimuli could be measured in
      rats. Such an animal model would provide a measure of aspects of information
      processing concerned with expectancy and time estimation. In a first experiment,
      omission evoked potentials (OEPs) were elicited in rats by omitting stimuli (10%)
      from a train of tone pips with a fixed ISI (3 s). A control session consisted of
      omitting stimuli (10%) from a train of tone pips with a variable ISI (2.5-3.5 s).
      In a second experiment, OEPs were measured in rats that received 4 mg x kg(-1)
      diazepam or vehicle sc. In the first experiment, half of the animals showed OEPs
      that consisted of a late-latency positive wave, the other rats showed a slow
      negative drift. No OEPs were found in the control session. Rats showing OEPs
      consisting of a positive wave in Experiment 1 were passed to Experiment 2. In the
      vehicle condition of the second experiment, all rats showed OEPs. In the diazepam
      condition no OEPs were found. We found that OEPs can be measured in rats. In
      addition, OEPs are disrupted by diazepam. We propose that OEPs provide an elegant
      tool to elicit selectively endogenous EP components.

PMID- 12212674
TI  - Effects of a dual task on the N100-P200 complex and the early and late Nd
      attention waveforms.
AB  - The roles of N100 and the early and late negative difference (Nd) waveforms in
      selective attention were investigated with primary simulated flying and secondary
      dichotic listening tasks. Twenty highly trained participants performed the two
      tasks together, either while detecting secondary task deviant tones in one ear
      and ignoring tones in the other ear (dual condition) or while ignoring the tones
      in both ears (ignore condition). The amplitude of the N100-P200 complex in both
      the dual-task and ignore conditions was reduced equally in the attended and
      unattended ear by the introduction of the primary task. In the dual-task
      condition, the amplitude of the late Nd but not the early Nd was reduced by a
      combination of the introduction of the primary task and an increase in its
      difficulty. P300 showed the same amplitude pattern as the late Nd. We propose
      that the reduction in N100-P200 amplitude reflects an automatic gating mechanism.
      The dissociation of the early and late Nd suggests that the latter is not
      modality specific. The question is raised whether the late Nd is more closely
      associated with P300 than with the early Nd.

PMID- 12212675
TI  - Comparison of finger plethysmograph to ECG in the measurement of heart rate
      variability.
AB  - Two experiments compared finger plethysmograph (FP) to electrocardiogram (ECG) in
      providing accurate heart periods for use in heart rate variability (HRV)
      calculations. In Experiment 1, simultaneous ECG and FP recordings were taken from
      16 healthy subjects at rest. In Experiment 2, 10 additional healthy subjects were
      recorded at rest and during the Stroop Color-Word Test. In both studies, high
      correlations were found between FP-derived and ECG-derived band variance for high
      and low frequency HRV at rest. But, during the Stroop task, correlations were
      strongly diminished. In addition, under both conditions, HRV measures were
      significantly higher using the FP signal. Thus, FP may be adequate for
      determining HRV at rest, but, for experimental use, ECG may still be recommended.
      Nonetheless, further studies that include test-retest reliability assessment of
      both data collection techniques are warranted before a more certain determination
      can be made.

PMID- 12212676
TI  - Startle potentiation in aversive anticipation: evidence for state but not trait
      effects.
AB  - The present study was undertaken to determine whether aversiveness contributes to
      startle potentiation in anticipation of affective pictures above and beyond the
      effects of emotional arousal. Further, participants high in trait anxious
      apprehension, which is characterized by worry about the future, were expected to
      show especially pronounced anticipatory startle responses. Startle blink reflex
      was measured during warning stimuli that predicted the valence of ensuing
      aversive/unpleasant, pleasant, or neutral pictures. Startle magnitude was larger
      in anticipation of aversive than of pleasant pictures and smallest in
      anticipation of neutral pictures. Enhanced startle potentiation was not found in
      anxious apprehension subjects. These data suggest that the aversive nature of
      stimuli contribute to the potentiation of startle above and beyond the effects of
      emotional arousal, which may be a universal phenomenon not modulated by
      individual differences.

PMID- 12212677
TI  - A direct threat to his patients: the application of disabilities law to HIV
      positive professionals in the dental practice setting.

PMID- 12212678
TI  - Mandibular growth following implant restoration: does Wolff's law apply to
      residual ridge resorption?
AB  - This study measured bone height under a fixed detachable cantilever restoration
      supported by five or six endosseous implants in 60 consecutively treated
      patients. Panoramic films were made at surgery and 1, 2, 3, and 4 years
      postrestoration. A computer-enhanced method was used to measure mandibular height
      5, 10, 15, and 20 mm distal to the last implant, which was used as a length.
      standard to correct for variation in film magnification. Implant restoration
      resulted in a significant growth of the mandible (baseline: 7.25 +/- 0.25 mm, 4
      years: 8.18 +/- 0.18 mm; P = .05). The growth in dimension appears to occur
      during the first year of function.

PMID- 12212679
TI  - GTR treatment of intrabony defects in patients with early-onset and chronic adult
      periodontitis.
AB  - Young, systemically healthy subjects may suffer from early-onset forms of
      periodontitis characterized by the presence of localized deep vertical bony
      defects. The aim of this study was to compare the healing response after guided
      tissue regeneration (GTR) treatment of similar intrabony defects in patients
      affected by early-onset and chronic adult periodontitis. Twenty systemically
      healthy, nonsmoking subjects were enrolled in the study; 10 were affected by
      early-onset periodontitis (EOP) and 10 by chronic adult periodontitis (CAP). In
      each subject, only one deep vertical bony defect (intrabony component > 4 mm,
      probing attachment level > or = 8 mm) was treated according to the principles of
      GTR therapy with titanium-reinforced e-PTFE membranes. At the time of the surgery
      and at the 1-year follow-up, a microbiologic test for the identification of the
      main periodontopathogens was performed in each of the treated sites. There was no
      statistically significant difference at 1 year in the amount of clinical
      attachment gain (P = .4), reduction of probing pocket depth (P = .3), or increase
      in gingival recession (P = 1.0) between EOP and CAP patients. The 1-year
      microbiologic results demonstrated the complete disappearance of the putative
      periodontopathogens from all surgically treated sites in both patient groups. The
      results of the study demonstrated that deep intrabony defects in patients with
      EOP can be successfully treated by means of GTR procedures and that the
      suppression of periodontopathogens under threshold values can be maintained for
      at least 1 year, provided that the patient is enrolled in a maintenance program
      consisting of recalls for professional tooth cleaning and reinforcement of self
      performed oral hygiene measures at 1-month intervals.

PMID- 12212680
TI  - HVC ridge deficiency classification: a therapeutically oriented classification.
AB  - Alveolar ridge defects resulting from tooth extraction, trauma, or periodontal
      disease often require surgical correction prior to prosthodontic reconstruction.
      Whether implants or conventional fixed prostheses are planned, without careful
      consideration and proper treatment planning, hard and/or soft tissue defects may
      lead to functional, structural, or esthetic compromises in the final prosthesis.
      This article reviews the etiology and treatment of alveolar ridge defects and
      introduces a therapeutically oriented classification system of such defects
      (horizontal, vertical, and combination-HVC-classification). In addition, a
      decision-making guide for approaching each defect type will be discussed, and
      clinical examples of treated cases will be presented.

PMID- 12212681
TI  - Healing of Osseotite implants under submerged and immediate loading conditions in
      a single patient: a case report and interface analysis after 2 months.
AB  - A growing number of clinical studies show that early (2 months) and immediate
      loading protocols may be predictable. However, they are based on clinical
      stability only The aim of this case report was to document the osseointegration
      status of two Osseotite implants after 2 months of healing in soft bone
      corresponding to type IV and subjected to two distinct mechanical environments. A
      completely edentulous patient received a total of 11 Osseotite implants in the
      mandible. Six were immediately loaded to support a provisional fixed partial
      denture, and five were left submerged. After 2 months, two submerged and one
      immediately loaded implants were retrieved and processed for histologic analysis.
      All immediately loaded implants were clinically stable. One histologic section
      per implant was obtained. All implants achieved osseointegration. The bone
      implant contact was 38.9% for the submerged implant and 64.2% for the immediately
      loaded one. In the marrow space, both implants were covered by thin, neoformed
      bone trabeculae. Osseointegration can be achieved after 2 months by Osseotite
      implants placed in soft bone in the mandible either when immediately loaded and
      splinted into a provisional denture retained on six implants, or when submerged
      and unloaded.

PMID- 12212683
TI  - The use of orthodontic intrusive movement to reduce infrabony pockets in adult
      periodontal patients: a case report.
AB  - Clinicians often encounter osseous defects that are best treated by conventional
      surgical techniques, including bone grafting and guided tissue regeneration, with
      a goal of establishing a new connective tissue attachment. On occasion, the
      recognition of an infrabony defect proximal to a tooth with a large diastema may
      present an opportunity to consider resolution by orthodontic tooth movement.
      Ideally, the tooth could be moved in the proximal direction until there was no
      further radiographic or clinical evidence of the predisposing defect. The authors
      decided to treat an advanced case of adult periodontitis, with extrusion and
      migration of a maxillary central incisor, using a multidisciplinary approach.
      Radiologically, a large infrabony defect was present on the mesial aspect of the
      incisor, with an initial probing depth of 9 mm. After the surgical periodontal
      therapy, the orthodontic movement started and the incisor was repositioned using
      an intrusive mechanism, also leading to the closure of the diastema. At the end
      of the treatment, there was a significant clinical decrease in the probing depth
      values, and radiographs showed a remarkable reduction of the infrabony defect
      volume.

PMID- 12212682
TI  - Comparative study of the physical properties of core materials.
AB  - This study was undertaken to measure physical properties of materials used for
      direct core buildups, including high-copper amalgam, visible light-cured resin
      composite, autocured titanium-containing composite, polyacid-modified composite,
      resin-modified glass-ionomer, and silver cermet cement. Compressive strength,
      diametral tensile strength, and flexural strength of six core materials of
      various material classes were measured for each material as a function of time up
      to 3 months at different storage conditions, using a standard specification test
      designed for the materials. Three different storage conditions (dry, humid, wet)
      at 37 degrees C were chosen. Materials were manipulated according to
      manufacturers' instructions for use as cores. Mean compressive, diametral
      tensile, and flexural strengths with associated standard deviations were
      calculated for each material. Multiple comparison and Newman-Keuls tests
      discerned many differences among materials. All materials were found to meet the
      minimum specification requirements, except in terms of flexural strength for
      amalgam after 1 hour and the silver cermet at all time intervals.

PMID- 12212684
TI  - Connective tissue graft: a classification for incision design from the palatal
      site and clinical case reports.
AB  - A classification system for connective tissue graft incisions is proposed. It
      categorizes the design of the palatal incision into three classes. In addition to
      the basic classification, two subclasses are mentioned in this article.
      Additional descriptions are included to further define the incision design. The
      use of such a classification should assist future communication among clinicians
      and researchers. This article presents representative clinical cases to aid the
      clinician in applying the classification for incision design from the palatal
      site.

PMID- 12212685
TI  - Treatment of furcation defects with an allograft-alloplast-tetracycline composite
      bone graft combined with GTR: human histologic evaluation of a case report.
AB  - The purpose of this study was to histologically evaluate furcation defects in
      humans treated with an allograft-alloplast-tetracycline composite graft combined
      with an absorbable membrane for guided tissue regeneration (GTR). Three teeth
      with Class II furcation involvement on the buccal aspects were included in this
      study. A notch was placed in calculus during the procedure to serve as a
      reference point for histologic evaluation. The defects were then treated with an
      allograft-alloplast-tetracycline composite graft combined with an absorbable
      membrane for GTR. At 6 months postoperative, the teeth were extracted with
      conservative block sections and processed for histologic evaluation. Regeneration
      (new bone, cementum, and connective tissue attachment) coronal to a notch could
      be seen in one of the three defects treated. In the other two defects, a new
      connective tissue attachment was demonstrated (new connective tissue attachment
      into new cementum) in the notch placed in calculus. In this study, regeneration
      of a furcation defect in a human was documented with histology.

PMID- 12212686
TI  - Effect of porous xenographic bone graft with collagen barrier membrane on
      periodontal regeneration.
AB  - The purpose of this study was to investigate the effect of porous xenographic
      bone graft (Bio-Oss) with a collagen barrier membrane (Bio-Gide) on formation of
      new cementum and new bone in experimental intrabony defects of dogs. The
      intrabony defects were treated by either guided tissue regeneration with the
      collagen membrane (control group) or the collagen membrane with the porous bone
      mineral graft (experimental group). After 8 weeks, the animals were sacrificed
      and the tissues were histologically examined. New cementum with inserting
      collagen fibers was observed on the exposed surfaces in both groups. The amount
      of nevv bone was significantly greater in the group using the bone graft with the
      membrane than in the control group. The use of the collagen barrier membrane in
      combination with the porous bone graft material may enhance new bone and cementum
      formation.

PMID- 12212687
TI  - Dual-etched implants loaded after 1- and 2-month healing periods: a histologic
      comparison in baboons.
AB  - The purpose of this study was to evaluate the effect of early loading of
      Osseotite dual acid-etched commercially pure titanium dental implants in an
      established baboon model. Implant sites were prepared by removal of premolars and
      first molars at maxillary and mandibular sites in 10 adult female baboons (Papio
      anubis). The resultant edentulous ridges were allowed to heal for 6 weeks.
      Following the placement of 80 implants, 2-mm healing abutments were placed on
      each implant and protruded through the mucosa after flap closure. Each implant
      was functionally loaded with a single crown after either 1 month (n = 40) or 2
      months (n = 40) of implant healing. All implants were removed in block section
      after 3 months of functional loading and prepared for histologic evaluation.
      Photographs of histologic slides were digitized for data collection. The amount
      of osseous tissue contact along the implant surface in the buccolingual plane was
      determined using image analysis. The fraction of direct bone-tissue contact along
      a standardized region of each implant perimeter was calculated and compared using
      analysis of variance. Implants loaded after 1 month of healing had a mean of
      76.6% + 14.4% bone contact, and implants loaded after 2 months of healing had a
      mean of 77.2% +/- 12.2% bone contact. Statistically, the 1- and 2-month groups
      were similar (P = .81). No implant failures were observed in either treatment
      group. Reducing the surgical healing time from 2 months to 1 month did not
      statistically affect the amount of bone observed at the tissue-implant interface
      in baboons under functionally loaded conditions.

PMID- 12212688
TI  - Identification and characterization of atrioventricular parasympathetic
      innervation in humans.
AB  - INTRODUCTION: We hypothesized that in humans there is an epicardial fat pad from
      which parasympathetic ganglia supply the AV node. We also hypothesized that the
      parasympathetic nerves innervating the AV node also innervate the right atrium,
      and the greatest density of innervation is near the AV nodal fat pad. METHODS AND
      RESULTS: An epicardial fat pad near the junction of the left atrium and right
      inferior pulmonary vein was identified during cardiac surgery in seven patients.
      A ring electrode was used to stimulate this fat pad intraoperatively during sinus
      rhythm to produce transient complete heart block. Subsequently, temporary
      epicardial wire electrodes were sutured in pairs on this epicardial fat pad, the
      high right atrium, and the right ventricle by direct visualization during
      coronary artery bypass surgery in seven patients. Experiments were performed in
      the electrophysiology laboratory 1 to 5 days after surgery. Programmed atrial
      stimulation was performed via an endocardial electrode catheter advanced to the
      right atrium. The catheter tip electrode was moved in 1-cm concentric zones
      around the epicardial wires by fluoroscopic guidance. Atrial refractoriness at
      each catheter site was determined in the presence and absence of parasympathetic
      nerve stimulation (via the epicardial wires). In all seven patients, an AV nodal
      fat pad was identified. Fat pad stimulation during and after surgery caused
      complete heart block but no change in sinus rate. Fat pad stimulation decreased
      the right atrial effective refractory period at 1 cm (280 +/- 42 msec to 242 +/-
      39 msec) and 2 cm (235 +/- 21 msec to 201 +/- 11 msec) from the fat pad (P =
      0.04, compared with baseline). No significant change in atrial refractoriness
      occurred at distances >2 cm. The response to stimulation decreased as the
      distance from the fat pad increased. CONCLUSION: For the first time in humans, an
      epicardial fat pad was identified from which parasympathetic nerve fibers
      selectively innervate the AV node but not the sinoatrial node. Nerves in this fat
      pad also innervate the surrounding right atrium.

PMID- 12212689
TI  - The atrioventricular nodal fat pad in humans: fat or fiction?

PMID- 12212690
TI  - Body surface area of ST elevation and the presence of late potentials correlate
      to the inducibility of ventricular tachyarrhythmias in Brugada syndrome.
AB  - INTRODUCTION: The value of noninvasive markers reflecting repolarization and/or
      conduction abnormalities in identifying patients with abnormal ECG showing a
      pattern of atypical right bundle branch block and ST elevation syndrome (Brugada
      syndrome) at risk for life-threatening arrhythmias is controversial. Because
      right precordial ST elevation reflects inhomogeneous repolarization, we
      hypothesized that a correlation between the area of ST elevation, that is, the
      area of inhomogeneous repolarization, and the inducibility of ventricular
      tachyarrhythmias (VT) exists. Therefore, the body surface area of ST elevation
      and the presence of late potentials were compared to the inducibility of VT in
      patients with the characteristic ECG of Brugada syndrome. METHODS AND RESULTS: A
      120-channel body surface potential map was recorded at rest and after
      administration of a Class I agent (ajmaline, 1 mg/kg) to measure the body surface
      area of ST elevation (> or = 0.2 mV) in 23 individuals (16 patients had been
      resuscitated from near sudden cardiac death or had suffered syncope) with an ECG
      compatible with the diagnosis of Brugada syndrome as well as in 15 healthy
      controls and in 15 patients with arrhythmogenic right ventricular cardiomyopathy.
      Late potentials were assessed in 20 of the Brugada patients using signal-averaged
      ECG. Programmed ventricular stimulation was performed at two ventricular sites
      with up to three extrastimuli. Mean body surface area of ST elevation (> or = 0.2
      mV) of all Brugada syndrome patients was 154 +/- 139 cm2 (control 9 +/- 9 cm2; P
      < 0.001). In the group of patients with arrhythmogenic right ventricular
      cardiomyopathy, only one patient was found to have an area of ST elevation (165
      cm2). In the presence of ajmaline, area size increased to 330 +/- 223 cm2 in
      Brugada syndrome patients (P < 0.05). In patients with inducible sustained (n =
      15) and nonsustained VT (n = 3), a mean area of 183 +/- 139 cm2 was found,
      whereas the area was only 52 +/- 58 cm2 in those with no VT induction (P < 0.05).
      For an area > or = 50 cm2, there were positive and negative predictive values of
      92% and 60%, respectively. Positive late potentials were found in 60% of patients
      and correlated to the inducibility during programmed ventricular stimulation
      (positive predictive value 100%, negative predictive value 75%; P < 0.001).
      CONCLUSION: In patients with Brugada syndrome, the body surface area of ST
      elevation and the presence of late potentials correlate to the inducibility of VT
      during programmed ventricular stimulation and may be of value as a new
      noninvasive marker for risk stratification in these patients.

PMID- 12212691
TI  - Usefulness of paced activation sequence mapping in catheter ablation of accessory
      pathways.
AB  - INTRODUCTION: Radiofrequency (RF) ablation of accessory pathways (APs) is often a
      time-consuming procedure, mainly because conventional criteria have modest
      accuracy. Thus, additional mapping criteria are desirable. Our hypothesis was
      that comparison of paced atrial activation sequences with that obtained during
      orthodromic AV reentrant tachycardia might be useful for locating the atrial
      insertion of single APs. METHODS AND RESULTS: The study included 15 patients with
      a single AP referred for ablation. Analysis of the atrial activation sequence was
      simplified by measuring the activation time (AT) that elapsed between two atrial
      reference points placed next to the AV annulus on either side of the area
      containing the AP. Ablation was guided by conventional criteria. Before each RF
      delivery, a short pacing train was delivered from the ablation catheter and,
      after verification of atrial capture, the AT was compared with the AT obtained
      during orthodromic tachycardia. Fifty sites of RF delivery were appropriate for
      analysis. The multivariate model with the highest predictive power included a
      deviation of AT between pacing and tachycardia < or = 5 msec (P < 0.001), a local
      AV ratio > or = 1 (P = 0.04), and stability of the local electrogram (P = 0.05).
      The combination of all these criteria predicted a successful application with
      high sensitivity, specificity, and positive predictive value (92%, 86%, and 71%
      respectively). To validate the method prospectively, 10 additional consecutive
      patients underwent an AP ablation procedure guided by these criteria. CONCLUSION:
      This technique seems to be highly accurate in selecting the atrial site for RF
      ablation of single APs.

PMID- 12212692
TI  - Prognostic significance of nonsustained ventricular tachycardia identified
      postoperatively after coronary artery bypass surgery in patients with left
      ventricular dysfunction.
AB  - INTRODUCTION: Nonsustained ventricular tachycardia (NSVT) occurs frequently in
      the postoperative period (< or = 30 days) after coronary artery bypass graft
      (CABG) surgery, a setting where many factors may play a role in its genesis. The
      prognosis of NSVT in this setting in patients with left ventricular (LV)
      dysfunction is unknown. This study was designed to assess its significance.
      METHODS AND RESULTS: We compared the outcome of untreated patients enrolled in
      the Multicenter Unsustained Tachycardia Trial with coronary artery disease (CAD),
      LV dysfunction, and NSVT identified postoperatively after CABG (n = 228; mean age
      67 years, 84% males) versus nonpostoperative settings (n = 1,302; mean age 66
      years, 85% males). Sustained monomorphic ventricular tachycardia was induced in
      27% and 33% (P = 0.046) of patients with postoperative and nonpostoperative NSVT,
      respectively. The 2- and 5-year rates of arrhythmic events were 6% and 16%,
      respectively, in postoperative patients versus 15% and 29% in nonpostoperative
      patients (unadjusted P = 0.0020, adjusted P = 0.0082). The 2- and 5-year overall
      mortality rates were 15% and 36%, respectively, for postoperative patients versus
      24% and 47% for nonpostoperative patients (unadjusted P = 0.0005, adjusted P =
      0.027). Patients whose NSVT was identified early (<10 days) versus late (10-30
      days) after CABG had significantly lower 2- (13% vs 23%) and 5-year (30% vs 52%)
      mortality rates (unadjusted P = 0.024, adjusted P = 0.018). CONCLUSION: In this
      population of patients with CAD and LV dysfunction, the occurrence of
      postoperative NSVT, especially within 10 days after CABG, portends a far better
      outcome than when it occurs in nonpostoperative settings. This suggests that in a
      such setting, NSVT represents a less specific risk factor for future events and
      should be considered when assigning risk and treatment of similar patients.

PMID- 12212693
TI  - Cerebrovascular complication associated with pulmonary vein ablation.
AB  - INTRODUCTION: Radiofrequency (RF) ablation has become an established treatment
      modality for patients with paroxysmal atrial fibrillation (AF). A principal
      limitation of RF catheter ablation is the risk of thromboembolism. Stroke as a
      complication after ablation of triggers of AF has not been previously reported.
      METHODS AND RESULTS: Fifty-six patients underwent RF ablation for a focal source
      of AF. Forty-nine patients (86%) had AF triggers in > or = 1 pulmonary vein. Mean
      procedure time was 227 +/- 74 minutes. Cerebrovascular event occurred in 3 (5%)
      patients, all >60 years old. Two of the three patients had a prior history of
      transient ischemic attacks. CONCLUSION: The risk of stroke from RF ablation may
      be higher in paroxysmal AF patients with prior transient ischemic attack.

PMID- 12212697
TI  - Exclusion of fluoroscopy during ablation treatment of right accessory pathway in
      children.
AB  - INTRODUCTION: The field of pediatric electrophysiology poses many challenges to
      electrophysiologists. In particular there are two major concerns: (1) to reduce
      the amount of fluoroscopy exposure to patients and medical staff in the
      catheterization laboratory and (2) to minimize the number of vascular accesses.
      Prolonged fluoroscopy times are associated with radiofrequency (RF) ablation of
      right accessory pathways (APs), particularly the right free-wall AP. The aim of
      this study was to eliminate the use of fluoroscopy during treatment of right
      sided APs in children while using a single-catheter approach. METHODS AND
      RESULTS: We studied 21 consecutive pediatric patients (mean age 11.3 +/- 3.2
      years) with Wolff-Parkinson-White syndrome due to a right AP. To limit
      fluoroscopy use, we used a three-dimensional navigation system that facilitated
      reconstruction of a three-dimensional electroanatomic activation map along the
      tricuspid annulus either on the atrial side during orthodromic AV reciprocating
      tachycardia or along the ventricular side during anterograde preexcitation. RF
      application was successful and without complications in 20 patients (success rate
      95%); moreover, 19 of the 21 patients underwent a single-catheter procedure. The
      remaining two patients required an additional quadripolar catheter for atrial
      stimulation. A mean of 2 +/- 1 RF applications were used during the whole study.
      CONCLUSION: Our study demonstrates that ablation of right APs in children can be
      performed without fluoroscopy using a single catheter with minimal amounts of RF
      applications. Our new technique is associated with high success rates.

PMID- 12212696
TI  - T wave alternans and ventricular arrhythmia risk stratification: uses and
      limitations.

PMID- 12212695
TI  - Influence of QRS duration on the prognostic value of T wave alternans.
AB  - INTRODUCTION: T wave alternans (TWA) is a promising new noninvasive marker of
      arrhythmia vulnerability that quantifies beat-to-beat changes in ventricular
      repolarization. Secondary repolarization abnormalities are common in subjects
      with wide QRS complexes. However, the relationship between TWA and QRS
      prolongation has not been evaluated. The goal of this study was to determine if
      QRS prolongation influences the prevalence or prognostic value of TWA. METHODS
      AND RESULTS: The study consisted of 108 consecutive patients with coronary artery
      disease and left ventricular ejection fraction < or = 40% who were referred for
      electrophysiologic studies. Patients underwent TWA testing using bicycle
      ergometry in the absence of beta-blockers or antiarrhythmic drugs. The primary
      endpoint was the combined incidence of death, sustained ventricular arrhythmias,
      and appropriate implantable cardioverter defibrillator therapy. The prognostic
      value of TWA was assessed in the entire cohort and in two subgroups: QRS < 120
      msec (normal, n = 62) and QRS > or = 120 msec (prolonged, n = 46). TWA (hazard
      ratio 2.2, P = 0.03) and QRS prolongation (hazard ratio 2.2, P = 0.01) were both
      significant and independent predictors of arrhythmic events. QRS prolongation had
      no effect on the prevalence of positive TWA tests (QRS < 120 msec: 48%, QRS > or
      = 120 msec: 50%, P = NS). TWA was a highly significant predictor of events in
      patients with a normal QRS (hazard ratio 5.8, P = 0.02). In contrast, TWA was not
      useful for risk stratification in subjects with QRS prolongation (hazard ratio
      1.1, P = 0.8). CONCLUSION: TWA is useful only for risk stratification in the
      absence of QRS prolongation. The presence of QRS prolongation and left
      ventricular ejection fraction < or = 40% may be sufficient evidence of an adverse
      prognosis that additional risk stratification is not useful or necessary.

PMID- 12212699
TI  - Increased intermittency and decreased nonstationarity of heart rates during the
      daytime in patients with neurocardiogenic syncope.
AB  - INTRODUCTION: During head-up tilt (HUT) test, patients with neurocardiogenic
      syncope show a sudden severe decrease in heart rate at the beginning of their
      induced syncopal attacks (termed intermittency). They also exhibit slow and
      progressive increases in their mean heart rates long before the induced syncopal
      attacks (termed nonstationarity). The aim of this study was to test our
      hypothesis that during daily activity, although not as prominently as during HUT
      test, patients show different degrees of intermittency and nonstationarity
      compared to healthy persons. METHOD AND RESULTS: Thirty patients with a positive
      HUT test and 30 healthy controls without a history of syncope were studied. The
      RR intervals of their 24-hour ambulatory ECGs were analyzed. To quantify the
      intermittency (C1) and nonstationarity (H1) behavior, multifractal analysis was
      performed using Mexican hat and Haar wavelet function, respectively. In the
      syncope group, C1 and H1 were significantly higher at 6 A.M.-6 P.M. and lower at
      6 A.M.-midnight, respectively. However, the values were not different at midnight
      6 A.M. The significant night-day circadian change shown in the control group was
      lost in C1 and diminished in H1. CONCLUSION: Patients with neurocardiogenic
      syncope show increased intermittency and decreased nonstationarity of heart rates
      in the daytime during daily activity, and abnormal night-day circadian changes of
      the intermittency and nonstationarity. These findings may be useful in the early
      identification of patients with neurocardiogenic syncope and in the investigation
      of abnormalities in heart rate regulating mechanisms.

PMID- 12212694
TI  - Potential benefits, risks, and complications of catheter ablation of atrial
      fibrillation: more questions than answers.

PMID- 12212698
TI  - Catheter tip cooling during radiofrequency ablation of intra-atrial reentry:
      effects on power, temperature, and impedance.
AB  - INTRODUCTION: Cooling the catheter tip either passively with increased tip size
      or actively during radiofrequency catheter ablation (RFCA) has been shown in
      canine thigh preparations to create larger lesions than standard catheter tips,
      yielding a theoretical advantage for improving the outcome of RFCA for intra
      atrial reentrant tachycardia (IART). METHODS AND RESULTS: The pediatric RFCA
      database at the Medical University of South Carolina was reviewed for RFCA of
      IART in patients with structural heart disease. From a total of 31 patients who
      underwent procedures during the study period, 8 patients in whom ablation with
      conventional ablation techniques failed and who went on to passive cooling with
      an 8-mm tip catheter or active cooling with an internally cooled-tip catheter
      were studied. Power delivery was greater but temperature and impedance were lower
      during cooled ablation than during conventional ablation. Passive cooling was
      associated with higher power than active cooling. These changes in RF biophysical
      characteristics were associated with successful elimination of 11 of 13 IART
      circuits in 7 of 8 patients. CONCLUSION: Cooling during RF ablation of atrial
      tachycardia clearly yielded greater power delivery in vivo and was associated
      with success.

PMID- 12212700
TI  - Characteristics of right atrial activation during coronary sinus pacing.
AB  - INTRODUCTION: Anatomic and electrical connections between the left atrium and
      right atrium (RA) have been described. The relationship between coronary sinus
      (CS) pacing site and RA activation has not been examined. METHODS AND RESULTS:
      Fifteen anesthetized swine underwent high-density noncontact mapping of the RA
      during pacing from up to five different sites within the CS. Isopotential mapping
      identified the site of earliest RA depolarization and the pattern of subsequent
      activation. Hearts were excised and endocardial dissection performed. Earliest RA
      activation occurred at the CS os with proximal CS pacing sites and at Bachmann's
      bundle at distal pacing sites. The mean depth at which a shift in earliest RA
      activation site occurred was 46 +/- 13 mm (range 21 to 63 mm). RA activation
      times following earliest activation at the CS and Bachmann's bundle were 40 +/- 4
      msec and 51 +/- 6 msec (P < 0.002). Conduction delay or block was recorded at the
      lateral cavotricuspid isthmus, terminal crest, and tendon of Todaro. Latest RA
      activation always occurred in the high anterolateral atrium after ascending the
      anterolateral wall. The lateral RA was activated by the wavefront that traversed
      the posterior wall rather than by the wavefront crossing the cavotricuspid
      isthmus, even with earliest RA activation at the CS os. CONCLUSION: The site of
      earliest RA activation during CS pacing is dependent upon the pacing depth within
      the CS. In the porcine heart, areas of conduction delay influence RA activation
      patterns and timings. These findings may have implications for patients
      undergoing assessment of radiofrequency ablation of atrial flutter.

PMID- 12212701
TI  - Aging-related increase to inducible atrial fibrillation in the rat model.
AB  - INTRODUCTION: Aging is associated with atrial interstitial fibrosis and increased
      incidence of atrial fibrillation (AF). We hypothesized that aged rats are
      suitable for study of aging-related AF and that partial atrial cellular
      uncoupling induced with heptanol in young rats mimics aging-related AF. METHODS
      AND RESULTS: Interatrial conduction time and atrial response to burst atrial
      pacing were evaluated in 11 young (2-3 months) and 12 old (22-24 months) male
      rats (Fisher 344) in the Langendorff-perfused setting. At baseline, sustained
      (>30 sec) atrial tachycardia (AT) and AF were induced in 10 of 12 and in 7 of 12
      old rats, respectively. No such arrhythmias could be induced in the young rats.
      Old rats had significantly (P < 0.01) longer interatrial conduction time and P
      wave durations than the young rats. Burst pacing failed to induce AT and AF in
      all 11 young rats studied. The effects of heptanol 2 to 10 microM were studied in
      both groups. Heptanol 2 to 5 microM promoted inducible AT in all 5 young rats
      studied; however, when its concentration was raised to 10 microM, AT could no
      longer be induced in any of the 5 young rats. No AF could be induced in any of
      the 5 young rats at heptanol concentrations of 2 to 10 microM. In the old rats,
      AF could still be induced during perfusion of 2 microM heptanol. However, when
      its concentration was raised to 5 and 10 microM, AF could not be induced in any
      of the 6 old rats studied. Optical mapping using a potentiometric dye showed a
      periodic single wavefront of activation during AT in both groups and 2 to 4
      independent wavefronts propagating in different directions during AF in the old
      rats. Histology revealed a significant increase in interstitial atrial fibrosis
      (P < 0.01), atrial cell size (P < 0.05), and heart weight in old versus young
      rats. Fibrosis in the old rats was highly heterogeneous. CONCLUSION: The rat
      model is suitable for study of aging-related AF. Uniform partial atrial cellular
      uncoupling with heptanol perfusion in the young rats, although promoting
      inducible AT, does not mimic aging-related AF. The results suggest that
      heterogeneous atrial interstitial fibrosis and atrial cell hypertrophy might
      contribute to the aging-related increase in atrial conduction slowing, conduction
      block, and inducible AF in the old rat model.

PMID- 12212704
TI  - Spontaneous T wave alternans and premature ventricular contractions during
      febrile illness in a patient with Brugada syndrome.
AB  - A 69-year-old man who had experienced syncope and ventricular fibrillation was
      referred to our hospital. ECG showed a right bundle branch block pattern with ST
      segment elevation in the right precordial leads. When the patient presented to
      the hospital with febrile illness, spontaneous T wave alternans and premature
      ventricular contractions were observed. When the patient became afebrile, ST
      segment elevation improved, and T wave alternans and premature ventricular
      contractions disappeared.

PMID- 12212706
TI  - How to enhance acute outcome of electrical cardioversion by drug therapy:
      importance of immediate reinitiation of atrial fibrillation.
AB  - INTRODUCTION: In almost 20% of patients with persistent atrial fibrillation (AF),
      electrical cardioversion is unsuccessful because of shock failure (i.e., no
      single sinus beat) or immediate reinitiation of AF (IRAF; recurrence within 2
      min). Relative prevalence of shock failure and IRAF are not well known because
      data on outcome of electrical cardioversion therapy mostly do not distinguish
      shock failure from IRAF. METHODS AND RESULTS: In this review, the role of
      pretreatment with antiarrhythmic drugs on prevention of shock failure and total
      outcome of the cardioversion procedure are investigated. Quinidine and
      propafenone seem to be effective in preventing IRAF. Verapamil given in addition
      to Class I or III drugs may strengthen the preventive effects of these drugs than
      if they were given alone. Ibutilide prevents shock failure, although neither
      ibutilide nor dofetilide seems to be effective in preventing IRAF. CONCLUSION:
      Pretreatment with antiarrhythmic drugs may enhance cardioversion outcome
      predominantly by preventing IRAF. Different antiarrhythmic drugs within the same
      Vaughan-Williams class have different effects on shock failure and IRAF.

PMID- 12212705
TI  - Circular mapping catheter entrapment in the mitral valve apparatus: a previously
      unrecognized complication of focal atrial fibrillation ablation.
AB  - Radiofrequency catheter ablation of focal atrial fibrillation triggers within the
      pulmonary veins is a rapidly developing therapy that relies on both recent
      technologies and evolving techniques. We describe the entrapment of a circular
      mapping catheter within the mitral valve apparatus after transseptal
      catheterization and mapping of the left atrium and pulmonary veins. The
      occurrence of this previously unreported complication stresses the need for
      continual monitoring and reporting of adverse effects from new devices and
      procedures to better inform patients and physicians of the benefits and risks of
      electrophysiologic interventions.

PMID- 12212702
TI  - Sustained inward current and pacemaker activity of mammalian sinoatrial node.
AB  - INTRODUCTION: A novel sustained inward Na+ current i(sv), which sensitive to Ca2+
      antagonists and potentiated by beta-adrenergic stimulation, has been described in
      pacemaker cells of rabbit, guinea pig, and rat sinoatrial node, as well as rabbit
      AV node. Although i(st) has been suggested to be an important pacemaker current,
      this has never been tested experimentally because of the lack of a specific
      blocker. In this study, we address the role of i(st) in the pacemaker activity of
      the sinoatrial node cell using computer models. METHODS AND RESULTS: The newly
      developed models of Zhang et al. for peripheral and central rabbit sinoatrial
      node cells and models of Noble and Noble, Demir et al., Wilders et al., and Dokos
      et al. for typical rabbit sinoatrial node cells were modified to incorporate
      equations for i(st). The conductance g(st) was chosen to give a current density
      voltage relationship consistent with experimental data. In the models of Zhang et
      al. (periphery), Noble and Noble, and Dokos et al., in which i(st) was smaller or
      about the same amplitude as other inward currents, i(st) increased the pacemaking
      rate by 0.6%, 2.2%, and 0.8%, respectively. In the models of Zhang et al.
      (center), Demir et al., and Wilders et al., in which i(st) was larger than some
      other inward ionic currents, i(st) increased the pacemaking rate by 7%, 20%, and
      14%, respectively. CONCLUSION: i(st) has the potential to be a regulator of
      pacemaker activity, although its importance will depend on the amplitude of i(st)
      relative to the amplitude of other inward currents involved in pacemaker
      activity.

PMID- 12212707
TI  - Scaling of atrioventricular transmission in mammalian species: an evolutionary
      riddle!
AB  - "Scaling deals with the structural and functional consequences of changes in size
      or scale among otherwise similar organisms." It plays a key role in all studies
      on comparative mammalian physiology and morphology. Heart weight is
      proportionally related to body weight and can be described by a straightforward,
      so-called allometric equation. We studied scaling of AV transmission times (PR
      intervals on the ECG) in 375 mammals of different dimensions and species. Scaling
      of AV transmission times versus heart length (third root of weight) is
      statistically best described by a S-shaped curve. This implies that AV
      transmission time in mammals is not linearly related to heart length and does not
      depend solely on the length of the AV transmission system. The AV node fine-tunes
      AV transmission times at rest and during exercise in individuals; it protects the
      ventricles against high-rate atrial arrhythmias such as atrial fibrillation; and
      it regulates basal AV transmission times in mammalian species of varying sizes.
      We call the "how" and "why" of the scaling of AV transmission time in mammals an
      evolutionary riddle that deserves further study.

PMID- 12212708
TI  - Mechanisms underlying atrioventricular nodal conduction and the reentrant circuit
      of atrioventricular nodal reentrant tachycardia using optical mapping.
AB  - The findings of multiple nondiscrete AV nodal pathways and asymmetric
      transitional zone provide a biophysical basis for understanding normal and
      abnormal AV node electrophysiology. Unidirectional block occurring at the
      transitional zone transforms the nondiscrete pathways model into a classic dual
      pathways physiology for AVNRT.

PMID- 12212703
TI  - Computational modeling studies in sinoatrial node cells.

PMID- 12212709
TI  - Narrow QRS complex tachycardia with alternating shorter and longer R-R cycles:
      what is the mechanism?

PMID- 12212710
TI  - Pilsicanide-induced marked T wave alternans and ventricular fibrillation in a
      patient with Brugada syndrome.

PMID- 12212711
TI  - A cool ablation.

PMID- 12212713
TI  - Definition of the atrioventricular node.

PMID- 12212712
TI  - Hot versus cool ablation.

PMID- 12212714
TI  - An evaluation of the effectiveness of a peer sexual health intervention among
      secondary-school students in Zambia.
AB  - This study investigated whether there were any changes in knowledge and normative
      beliefs regarding abstinence and condoms and personal risk perception of
      acquiring HIV among Zambian secondary-school students who were exposed to a peer
      sexual health intervention. Schools were randomly assigned to intervention and
      control groups. A baseline assessment that measured knowledge, normative beliefs
      about abstinence and condoms and personal risk perception was conducted in all
      schools. Students in the intervention group were exposed for a 1-hour-and-45
      minute-long in-class peer sexual health intervention. Students in the control
      schools were exposed to a 1-hour-long in-class peer water purification
      intervention. A follow-up assessment of students was conducted after the
      intervention. Logistic regression analyses were conducted to determine whether
      significant differences between intervention and control groups emerged at follow
      up. Relative to students in the control group, knowledge was higher and normative
      beliefs about abstinence and condoms were significantly more positive among
      students in the intervention schools. Students in the intervention schools also
      had a higher personal risk perception of acquiring HIV than students in control
      schools. These findings show that a school-based peer sexual health intervention
      implemented in Zambia was effective in increasing knowledge, positive normative
      beliefs about abstinence and condoms, and personal risk perception.

PMID- 12212715
TI  - The impact of utilizing HIV-positive speakers in AIDS education.
AB  - A longitudinal matched control study was conducted to evaluate the effects on
      young people (n = 1,280) of talks by HIV-positive speakers who disclose their
      personal perspective of living with HIV. Focus-group discussions with students (n
      = 117) were used to elucidate the impact. Meeting HIV-positive people decreased
      fear and prejudice, reinforced messages about protective behavior and increased
      the belief that HIV is preventable. Improved attitudes after talks by females
      remained significant over 3 months. Speakers changed perceptions, broke down
      stereotypes, and made students realize that anybody is vulnerable to infection.
      The speaker provided an anonymous, nonjudgmental person to whom young people
      could easily relate. They opened the doorway to discussions about AIDS. AIDS
      interventions must focus on recruiting, supporting and training young articulate
      HIV-positive people, particularly females, to deliver sex education to in- and
      out-of-school youths. HIV-positive speakers have an essential role to play in
      AIDS prevention and must be utilized appropriately.

PMID- 12212716
TI  - Characteristics and predictors of HIV risk behaviors among injection-drug-using
      men and women in St. Petersburg, Russia.
AB  - The purpose of this study was to establish the prevalence of high-risk sexual
      behaviors and drug-using behaviors in a large community sample of male and female
      injection drug users (IDUs) in St. Petersburg, Russia. This investigation used a
      data collection plan that systematically recruited a drug user sample from venues
      where IDUs were known to congregate and could be accessed. Surveys were completed
      by 239 IDUs (males = 139, females = 100), aged 13-25. Participants averaged 44
      injections (range = 0-240) in the past 30 days, with heroin (70%) and heroin plus
      other drugs (20%) the most frequently used. Participants' mean age of first drug
      injecting was 17.6 years, 41% of participants regularly shared needles, most had
      multiple sexual partners (mean = 9.3 partners in the past 3 months), and 70%
      reported engaging in vaginal intercourse without condoms. Stepwise logistic
      regression showed that high-risk sexual behavior was predicted by being female,
      young, using heroin several times a month, and less negative attitudes toward
      using condoms. Effective HIV prevention efforts for IDUs in Russia must be
      tailored to their age, gender, drug use, and condom attitudes. These programs
      will also have to address the dual risk factors, unique to IDUs, of risky sexual
      behaviors and needle sharing. Without a rapid intervention response, Russia's
      HIV/AIDS crisis will soon turn catastrophic.

PMID- 12212717
TI  - Behavioral surveillance and factors associated with condom use and std incidences
      among the male commercial sex client population in Hong Kong--results of two
      surveys.
AB  - The present study compared the results of behavioral surveillance data obtained
      on the male clients of female sex workers (FSWs) population in Hong Kong. Two
      surveys, using an identical method, were completed in 1998 and 2000.
      Respectively, 1,020 and 2,074 respondents aged 18-60 who were randomly selected
      from the general population participated in the study. About 12% of the
      respondents had patronized FSWs in the past 6 months in 2000 as compared with 14%
      in 1998 (p = .143). Crossing the border for sex and purchasing sex in multiple
      geographic areas was very common and a higher percentage of respondents reported
      having patronized FSWs in mainland China in 2000 than in 1998 (p = .003). About
      25% of the respondents in both surveys had not always been using condoms (i.e.,
      not used condoms every time) when having sexual intercourse with FSWs. Those who
      practiced commercial sex in mainland China were less likely to have always been
      using condoms with FSWs (p < .01) and were more likely to have ever contracted
      STD in the past 6 months (p < .05), when compared with those who had purchased
      sex only in Hong Kong or in other places.

PMID- 12212719
TI  - Sexual assertiveness in heterosexually active men: a test of three samples.
AB  - Heterosexually active men have great potential to increase condom use rates
      during sexual encounters. However, this potential cannot be realized if men are
      not assertive with their partners regarding condom use. This study reports on the
      examination of condom-specific sexual assertiveness (SA) in three independent
      samples of heterosexually active men. In so doing, a reliable and brief four-item
      measure of SA was developed from a measure previously used with women. Across all
      three samples, those with higher SA were significantly more likely to be further
      along the condom stages of change, and significantly less likely to have engaged
      in unprotected sex. Results suggest that SA is a meaningful construct for men and
      that increasing SA in men may result in subsequent increases in safer sexual
      behaviors.

PMID- 12212718
TI  - Secret pills: HIV-positive patients' experiences taking antiretroviral therapy in
      North Carolina.
AB  - Understanding the barriers to antiretroviral adherence is a critical step in
      improving the effectiveness of HIV treatment and saving lives. We sought to
      assess, qualitatively, the experiences of HIV-positive persons taking
      antiretroviral therapy (ART) in North Carolina. Twenty-four people participated
      in one of six focus groups. A structured interview script included three
      questions (two open-ended) and eight probes. Each discussion was taped,
      transcribed, and content-analyzed. Three distinct themes emerged. First, many
      participants believed that taking ART was lifesaving but missed doses because
      they feared that taking them in public would reveal their HIV status. Second, as
      a result, participants often found it difficult to integrate their regimens into
      the most basic daily activities. Finally, participants stressed the importance of
      having open, ongoing dialogues about their treatment plans and privacy needs with
      a wide range of health care workers. Multidimensional, tailored interventions may
      help persons living with HIV overcome the stigma and other complex barriers they
      face in taking antiretroviral therapy.

PMID- 12212720
TI  - A response to "developing standards in behavioral surveillance for HIV/STD
      prevention".

PMID- 12212721
TI  - The current good should precede the future best: a response to a response.

PMID- 12212722
TI  - Comparison of sampling procedures for isolating pulmonary mycoplasmas in cattle.
AB  - Three sampling procedures were compared to determine the optimal technique for
      isolating mycoplasmas in cattle with respiratory diseases. The prevalence of
      mycoplasmas isolated from these animals is also reported. In the first group,
      bronchoalveolar lavage (BAL) and nasal swab cultures were compared with the
      corresponding lung cultures from cattle necropsied for fatal respiratory diseases
      (n = 20). In a second group, nasal swabs were compared with corresponding BAL
      cultures in living animals with recurrent respiratory pathologies (n = 49). There
      was complete agreement between the paired BAL and lung cultures. In contrast,
      nasal cultures were not representative of the mycoplasmas present in the lower
      respiratory airways. The relative sensitivity and specificity of the nasal swab
      technique compared to BAL in living animals confirmed that the nasal swab
      cultures were not predictive of lower respiratory airway pathogens, such as
      Mycoplasma bovis. BAL is considered to be the best method for isolating M. bovis
      in cattle with respiratory diseases as it combines reliability and feasibility
      under field sampling conditions. In the present study, Mycoplasma dispar (43%)
      and M. bovis (29%) were mainly isolated in mixed infections. This confirms the
      need to search for mycoplasmas in routine examinations and to take them into
      account in therapeutic strategies for respiratory diseases in cattle.

PMID- 12212724
TI  - Changes in activities of enzymes related to energy metabolism in testicular
      tissues of dogs with seminoma.
AB  - Changes in the activities of enzymes related to energy metabolism in the
      testicular tissues of dogs with seminoma were investigated. The testis was
      removed surgically from animals anaesthetized with halothane. Cytosolic and
      mitochondrial fractions were isolated and the total RNA was extracted from
      testicular homogenates. The activities of enzymes related to energy metabolism
      were measured and the mRNA of cytosolic malate dehydrogenase (MDH) was
      investigated by the reverse transcriptase-polymerase chain reaction (RT-PCR). The
      activities of the glycolytic enzymes glucose-6-phosphate dehydrogenase (G6PD) for
      the pentose phosphate pathway and malate dehydrogenase (MDH) for the malate
      aspartate shuttle, and the expression of the mRNA of cytosolic MDH were
      significantly increased in the testicular tissues of dogs with seminoma. These
      enzymatic activities may be useful indicators with which to evaluate changes in
      the metabolic conditions in testicular tissues of dogs with seminoma.

PMID- 12212723
TI  - The activity ratio of the cytosolic MDH/LDH and the isoenzyme pattern of LDH in
      the peripheral leukocytes of dogs, cats and rabbits.
AB  - The activities of malate dehydrogenase (MDH) and lactate dehydrogenase (LDH) and
      the pattern of the isoenzymes of LDH were determined in the peripheral blood
      leukocytes of dogs, rabbits and cats. Rabbits had significantly higher plasma
      glucose concentrations than dogs or cats. Feline leukocytes showed higher LDH and
      lower MDH activities than canine or rabbit leukocytes. The M/L ratio, defined as
      the MDH activity divided by the LDH activity in cytosolic fractions, was
      considered to be a good indicator with which to evaluate the metabolic state in
      animal tissues. The M/L ratio was highest in canine and lowest in feline
      leukocytes. LDH-2 and LDH-3 isoenzymes were dominant in canine leukocytes. LDH-1
      and LDH-2 were dominant in rabbit leukocytes, whereas LDH-5 was dominant in
      feline leukocytes. It was evident that there were significant differences in
      energy metabolism between the leukocytes of dogs, rabbits and cats.

PMID- 12212725
TI  - Observations on haemoglobin types in three breeds of Omani goats.
AB  - Haemoglobin (Hb) types were studied in three breeds of Omani goats, Batinah (n =
      22), Jebel Akhdar (n = 27) and Dhofari (n = 85). Type A was the only adult Hb
      observed in adult Batinah and Jebel Akhdar goats. In contrast, only 34% of the
      Dhofari goats were homozygous for Hb A, while 66% were heterozygous for Hb A and
      Hb B. Dhofari goats with type AB could further be differentiated into those with
      approximately 67% type A and 33% type B and those with approximately 33% type A
      and 67% type B. None of the goats was homozygous for type B. Seventeen kids
      observed from birth exhibited different levels of fetal Hb, dependent upon
      whether they developed the adult phenotype AA or AB. Kids that became homozygous
      for type A were born with approximately 90% Hb F and 10% Hb A. In contrast, goats
      that developed the heterozygous AB phenotype were born with only 30-60% Hb F, the
      remaining Hb being types A and B. These findings are not in accordance with
      previous reports that kids are born without any adult Hb. Hb F was no longer
      detectable in any of the three breeds of goats at 49 days of age. There was no
      evidence of Hb C, the pre-adult form of Hb.

PMID- 12212726
TI  - Influence of age and breed on natural bovine fasciolosis in an endemic area
      (Galicia, NW Spain).
AB  - An analysis was undertaken of the effect of breed and age on bovine fasciolosis
      using antibody and antigen detection ELISAs. A total of 84.3% of the 1284 serum
      samples examined had positive antibody values and 20.4% exhibited antigenaemia.
      The seroprevalence of antibodies in crossbred cattle was higher than that in
      autochthonous Rubia Gallega, Friesian or Brown Swiss cows. The highest percentage
      antigenaemia occurred in the Brown Swiss cattle, but the breed differences were
      not statistically significant. Cattle aged 3-5 years had the highest antibody and
      circulating antigen prevalence and the age differences were significant. It was
      concluded that the apparent influence of breed was probably closely associated
      with the husbandry system. The autochthonous Rubia Gallega may be better adapted
      to fasciolosis as its percentage of antigenaemia was the lowest.

PMID- 12212727
TI  - Endometrial tissue concentrations of enrofloxacin after intrauterine
      administration to mares.
AB  - Endometritis in mares is a common cause of infertility. Conventional treatments
      of the disease have mostly been unsuccessful, so new therapeutic alternatives
      need to be investigated. This study evaluated the uterine disposition and plasma
      pharmacokinetic behaviour of a commercial formulation of enrofloxacin (EFX) given
      by the intrauterine (i.u.) route (2.5 mg/kg) in healthy mares. In order to
      evaluate the uterine inflammatory response, an initial histopathological study
      assessing polymorphonuclear cell infiltration was carried out in 20 mares over a
      14-day period after treatment. In a second study, 6 healthy adult mares were used
      for the pharmacokinetic study. Samples of uterine tissue and plasma were
      collected from 0 to 24 h after the i.u. treatment with 5% EFX solution. Samples
      were analysed by conventional microbiological assay using an EFX-sensitive strain
      of Escherichia coli (ATCC 25922). There was a moderate but statistically
      nonsignificant inflammatory response following i.u. administration of either the
      formulation or the vehicle alone. Pharmacokinetic analysis of the uterine
      concentrations of EFX showed a slow and sustained depletion, with EFX remaining
      at concentrations above the MIC for 24 h after treatment. The area under the
      concentration-time curve obtained for the uterus suggested that EFX and its
      metabolites are specifically retained in the uterus, which is the target tissue
      for bacterial colonization. Neither study provided any evidence of EFX toxicity.
      In conclusion, these results are encouraging and suggest that EFX may be a useful
      local treatment in mares with bacterial endometritis.

PMID- 12212728
TI  - Accumulation of sapogenin conjugates and histological changes in the liver and
      kidneys of lambs suffering from alveld, a hepatogenous photosensitization disease
      of sheep grazing Narthecium ossifragum.
AB  - Sixteen lambs exhibiting hepatogenous photosensitization (alveld) after grazing
      pasture containing Narthecium ossifragum and seven nonphotosensitized lambs
      grazing the same pastures were studied. All the alveld-affected lambs revealed
      liver damage dominated by single cell necrosis, portal fibroplasia and bile duct
      proliferation. Crystalloid clefts were demonstrated in the bile ducts of two and
      in the hepatocytes and Kupffer cells of nine photosensitized lambs. Plasma
      bilirubin concentration was severely increased in ten of the cases of alveld
      whereas the activity of aspartate aminotransferase was moderately to severely
      increased in seven cases. The activity of glutamate dehydrogenase was moderately
      elevated in one of the photosensitized lambs. The main histopathological findings
      in the kidneys from the alveld-affected lambs were dilated tubules, often with
      eosinophilic material in the tubular lumina. Regenerative changes were seen in a
      large proportion of the renal sections. Elevated plasma concentrations of urea
      and creatinine, and the renal histopathological changes, suggested that the
      photosensitized lambs had been through a phase of renal injury. Analysis of the
      free and conjugated sapogenin content in liver tissue and bile was performed by
      gas chromatography-mass spectrometry. There were significantly higher
      concentrations of conjugated episapogenins in both the liver and bile in the
      alveld-affected lambs than in the nonphotosensitized lambs.

PMID- 12212729
TI  - Comparative impact of live chicken infectious anaemia virus vaccine versus
      natural exposure in meat chicken breeders on immunity to infectivity by CIA and
      inclusion body hepatitis viruses in their offspring.
AB  - The immunology and histopathology and the distribution of viral antigen in
      infections with chicken infectious anaemia virus (CIAV) and inclusion body
      hepatitis virus (IBHV) were compared in the broiler offspring of CIAV-vaccinated
      meat chicken breeders versus those in the offspring of breeders naturally exposed
      to field CIAV. No significant difference in the humoral antibody level specific
      for CIAV was observed between 5 and 33 weeks of age in the two breeder groups (p
      > 0.05). The maternal humoral immunity to CIAV in the day-old offspring of the
      groups did not differ significantly (p > 0.05). The humoral immunity to CIAV at
      40 days of age indicated an absence of clinical signs of CIAV in the broiler
      offspring of both groups of breeders and this was associated with mean serum
      thymulin levels in offspring of both groups not differing significantly at 1 or
      40 days of age. Histopathological and immunofluorescence observations did not
      differ significantly in the offspring of either group by CIAV or IBHV.

PMID- 12212731
TI  - Dynamic mechanical analysis of the SAN co-polymer and the SBR latex co-mixture.
AB  - Useful experimental data based on the dynamic effects of the SAN/SBR mixture at
      higher temperatures were acquired. This data can allow us to gather information
      about the molecular motion and any interesting behavior of this mixture at
      elevated temperatures and increases in the SAN to SBR weight proportion. The
      importance of dynamic mechanical experiments of multi-phase polymer systems is
      presented. A series of (SAN/SBR) co-mixed samples were prepared with varying
      weight proportions over a temperature interval. TBA equipment (a type of
      torsional braid set of equipment) was used to make the dynamic mechanical
      analysis of the SAN/SBR co-mixture.

PMID- 12212730
TI  - Susceptibility of bovine umbilical cord endothelial cells to bovine herpesviruses
      and pseudocowpox virus.
AB  - The purpose of the study was to determine the susceptibility of bovine umbilical
      cord endothelial (BUE) cells to bovine herpesvirus (BHV) 1, BHV2, BHV4 and BHV5,
      and to pseudocowpox virus. The detection limits and growth curves of these
      viruses in BUE cells were compared with those in Vero, Madin-Darby bovine kidney
      (MDBK). or bovine fetal diploid lung (BFDL) cells. Detection limits were
      determined by inoculating cell cultures with serial 10-fold dilutions of these
      viruses, and growth curves by titration of virus, harvested at various times
      after infecting cells at a multiplicity of infection of 0.1. The detection limits
      of BHV2 and BHV4 were lower in BUE cells than in Vero or MDBK cells, and
      cytopathic effects were observed earlier in BUE cells. In addition, BHV2 and BHV4
      grew to higher titres in BUE cells than in Vero or MDBK cells. BUE cells appeared
      to be equally susceptible to BHV5, but less susceptible to BHV1.1 and BHVI.2 than
      MDBK cells. The study showed that BUE cells are highly susceptible to BHV2 and
      BHV4. and that the use of BUE cells can improve the laboratory diagnosis of these
      viruses. The use of BUE cells could also improve the isolation and growth of
      pseudocowpox virus.

PMID- 12212732
TI  - 2D 1H and 13C NMR evidences of the [2 + 2] autodimerization of 2-benzyl-5
      benzylidene cyclopentanone yielding two different diphenyl, dispiro cyclobutane
      derivatives.
AB  - The ene-ene [2 + 2] cycloaddition of 2-benzyl-5-benzylidenecyclopentanone
      proceeds smoothly and spontaneously in benzene-d6 or deuteriochloroform solution
      to give two different diphenyl dispiro [4.1.4.1] dodecan-4,11-diones. Detailed 1H
      and 13C 2DNMR spectroscopy (COSY, HMQC, HMBC) were performed in order to prove
      the existence in solution of two cyclobutane derivatives, one a previously
      described photodimer obtained by the UV irradiation of crystals of 2-benzyl-5
      benzylidenecyclopentanone.

PMID- 12212733
TI  - The effect of catalyst concentration on the synthesis of single-wall carbon
      nanotubes.
AB  - Single wall carbon nanotubes (SWNTs) were synthesized by electric arc discharge
      method with a mixture of nickel and yttrium as catalysts. The effect of the
      catalyst concentration on the synthesis of SWNTs was studied. Raman spectra of
      SWNTs have been recorded with excitation wavelengths from 476.5 to 1064 nm. The
      Raman peaks of the radial breathing modes (RBM) of SWNTs were assigned. The
      results indicate that the diameter distribution of SWNTs is in the range of 1.2
      1.6 nm, and the SWNTs with diameter 1.43 nm are in the majority. The catalyst
      concentrations have large effect on the yield of SWNTs and little effect on the
      diameter distribution of SWNTs.

PMID- 12212734
TI  - Ion-molecule interactions in solutions of lithium perchlorate in propylene
      carbonate + diethyl carbonate mixtures: an IR and molecular orbital study.
AB  - FTIR spectra have been recorded and analyzed for solutions of lithium perchlorate
      in propylene carbonate (PC), diethyl carbonate (DEC), and PC + DEC mixtures. It
      has been shown that the carbonyl stretch bands for PC and DEC are very sensitive
      to the interaction between Li+ and the solvent molecules. They split with
      addition of LiClO4, indicating a strong interaction of Li+ with PC and DEC
      through the oxygen group of PC and both oxygen and ether oxygen atoms of DEC. In
      conjunction with molecular orbital calculation, the optimized geometries of
      solvation are given. In addition, solvent separated ion pairs and contact ion
      pairs were observed in LiClO4/DEC solutions, and no preferential solvation of Li+
      in LiClO4/PC + DEC solutions were detected.

PMID- 12212735
TI  - Infrared spectroscopy of SO2 aqueous solutions.
AB  - The chemistry of SO2 solutions was studied with infrared transmission and total
      internal reflection (ATR) spectroscopy. The cross-sections of the SO2 stretching
      vibrations v1, v3 and the combination band of v1 + v3 were obtained and found to
      be slightly different from their gas phase values. Six features we associate with
      sulfur-containing ions were observed. We present the first infrared evidence for
      the bisulfite ion HOSO2- through detection of its OH stretching vibration. Other
      features may be associated with HSO3-, another isomer of the bisulfite ion, and a
      new compound we propose to be H2S2O6(2-). We found no evidence for sulfurous acid
      H2SO3.

PMID- 12212736
TI  - Optical studies of Eu3+ ions doped in tellurite glass.
AB  - Absorption and fluorescence spectra of Eu3+ ions doped in a tellurite glass have
      been recorded and analysed. Judd-Ofelt analysis has been done in order to
      calculate the different optical parameters such as oscillator strength, Judd
      Ofelt intensity parameters, stimulated emission cross-section, transition
      probability, branching ratio, radiative lifetime, etc. Lifetime measurements of
      the 5D0 level as a function of Eu3+ concentration have been used to explore the
      concentration quenching process. The mechanism of quenching is found to be of a
      dipole-dipole type.

PMID- 12212737
TI  - AM1 CI and ZINDO/S study of quaternary salts of diazaphenanthrenes with
      haloalkanes.
AB  - For quaternary salts of diazaphenanthrenes 1-3 with methyl iodide 4-6,
      diiodomethane 7-9 and 1,2-dibromoethane 10-12 UV spectral values have been
      calculated by AM1 CI, and in the case of 4-6 also with ZINDO/S method.
      Correlations of experimental and calculated wavenumber values of considered
      compounds show good compatibility. For geometry optimisation of 4-9 the AM1 CI
      method has been used.

PMID- 12212738
TI  - Nonlinear optical properties of diazabutadienes and -hexatrienes; experimental
      and computational aspects.
AB  - Donor-acceptor substituted diazabutadienes and -hexatrienes were prepared by
      straightforward procedures and their linear optical (UV-vis) and nonlinear
      optical second harmonic generation (SGH) properties investigated in a combined
      theoretical and experimental study. Theoretical and experimental results were in
      reasonable agreement. For the compounds in this study, which contained a p
      nitrophenyl group as electron acceptor, the p-dimethylaminophenyl group was the
      most powerful electron-donating group, leading to the highest maximum absorption
      wavelengths, as well as to the maximum SHG efficiency.

PMID- 12212739
TI  - Spectroscopic studies and normal coordinate analysis of bilirubin.
AB  - The infrared spectrum of bilirubin has been recorded in the spectral region 200
      4000 cm(-1). The Raman spectrum has also been recorded using the second harmonic
      (530 nm) radiation of a 200 mW Nd-YAG laser. In order to confirm the vibrational
      assignment of the bands obtained from experimental observation, a normal
      coordinate analysis has been carried out using the semi-empirical AM1 method
      through MOPAC 5.1 computer program. Electronic absorption spectrum of bilirubin
      dissolved in CHCl3 has been recorded in the spectral region 300-600 nm. A broad
      spectrum is observed with peak maxima at 454.2 nm. The photoacoustic spectrum of
      this molecule (in the powder form) has also been recorded for the first time
      which shows certain discrete features.

PMID- 12212740
TI  - Studies on synthesis and infrared and fluorescence spectra of new europium and
      terbium complexes with an amide-based open-chain crown ether.
AB  - An amide-based open-chain crown ether ligand and its complexes with europium and
      terbium were synthesized. The complexes were characterized by elemental analysis,
      infrared spectra and conductivity. The europium and terbium ions were found to
      coordinate to the C=O oxygen atoms and pyridine nitrogen atoms. The fluorescence
      properties of these complexes in DMF and CH3OH/CHCl3 were studied. Under the
      excitation of UV light, these complexes exhibit characteristic fluorescence of
      europium and terbium ions. The solvent factors influencing the fluorescent
      intensity are discussed.

PMID- 12212741
TI  - Potentiometric-spectroscopic evaluation of metal-ion complexes by humic fractions
      extracted from corn tissue.
AB  - Humic fraction (HF) functional group-type and content are expected to depend on
      molecular size, which in turn, is expected to influence formation of heavy-metal
      complexes. In this study, corn (Zea mays L.) stalks and leaves were decomposed
      for an 8-month period to produce water-soluble humic substances. These substances
      were separated into three water-soluble fractions, HF1, HF2 and HF3, from highest
      to lowest relative molecular size. Functional group determination showed that
      carboxylic, and phenolic OH acidity increased as relative molecular size of humic
      fractions decreased. We also observed decreasing C/O ratios from larger to
      smaller corn tissue-derived humic fractions, whereas N/C and H/C ratios remained
      relatively unaffected. Furthermore, using potentiometric titration and FTIR
      spectroscopy we studied formation of Ca2+-, Cd2+-, and Cu2+-humic fraction
      complexes and how they were affected by pH and molecular size. We determined that
      metal-humic complexes exhibited at least two types of functional group-sites with
      respect to Ca2+, Cd2+, and Cu2+ complexation. Strength of metal-ion humic
      complexes followed the order Cu2+ > Cd2+ > Ca2+ and was affected by pH,
      especially for low affinity sites. Carboxylic groups were most likely the
      dominant group-sites involved in complex formation. Magnitude of the metal-humic
      formation constants in the logarithmic form at the lowest equilibrium metal-ion
      concentration, under the various pH values tested, varied from 5.39 to 5.90 for
      Ca2+, 5.36 to 6.01 for Cd2+, and 6.93 to 7.71 for Cu2+. Furthermore, the
      formation constants appeared to be positively influenced by decreasing molecular
      size of water-soluble humic fraction, and increasing pH. However, our molecular
      spectra showed that the pKa of corn humic fractions increased with decreasing
      relative molecular size and that Cu2+ was more covalently bonded by humic
      fractions than were Ca2+ and Cd2+, and the nature of the covalent bond character
      was independent of pH.

PMID- 12212742
TI  - Determination of the ground state, excited state and change in dipole moments of
      magnesium and zinc chlorin.
AB  - High-resolution Stark effect measurements on the S1 <-- S0 (pi pi*) origin of
      magnesium chlorin (MgCh) and zinc chlorin (ZnCh) in single crystals of n-octane
      at 4.2 K are reported. The corresponding change in dipole moment (absolute
      value(delta mu(ge))) associated with each transition was estimated to be 0.23 +/-
      0.04 and 0.27 +/- 0.05 debye, respectively. Each molecule's orientation in the n
      octane crystal was also determined. The change in dipole moment of MgCh was also
      found using solvatochromic shift data (absolute value(delta mu(ge))) = 0.33 +/-
      0.08 debye). The ground state dipole moment (mu(g)) of MgCh was determined by
      dielectric constant measurement of MgCh/benzene solutions (mu(g) = 2.26 +/- 0.08
      debye). These were combined to calculate the average excited state dipole moment
      of MgCh (mu(e) = 2.51 +/- 0.08 debye). The ground state dipole moment of ZnCh was
      also determined using solvatochromic shift data (mu(g) = 3.17 +/- 0.08 debye).
      This was combined with its measured absolute value(delta mu(ge)) to calculate the
      excited state dipole moment of ZnCh (mu(e) = 3.44 +/- 0.08 debye); the S1 <-- S0
      (pi pi*) origin band of both complexes was red-shifted at room temperature as the
      polarity of the solvents was increased, which implies that delta mu(ge) is
      positive.

PMID- 12212744
TI  - Spectroscopic study of the E(4)1sigma+ state in NaLi.
AB  - Polarization labelling spectroscopy is applied to study the excited E1sigma+
      state of NaLi in the energy range 26,500-28,000 cm(-1) above the bottom of the
      ground state. The potential curve of the E state is constructed using the
      Inverted Perturbation Approach method. The values of Te, omega(e) and Re are
      found to be 26,474.82(4), 180.3(2) cm(-1) and 3.343(1) A, respectively.

PMID- 12212743
TI  - Studies on properties and application of non-protected room temperature
      phosphorescence of propranolol.
AB  - A direct and simple non-protected room temperature phosphorimetry (NP-RTP) for
      determine propranolol, which using I- as a heavy atom perturber and sodium
      sulfite as a deoxygenator, has been developed. The phosphorescence peak
      wavelength maxima lambda(ex)/lambda(em) = 288/494, 522 nm. The analytical curve
      of propranolol gives a linear dynamic range of 8.0 x 10(-8)-2.0 x 10(-5) mol l(
      1) and a detection limit of 3 x 10(-8) mol l(-1). The influence of I-
      concentration on RTP lifetime of propranolol was studied and the luminescence
      kinetic parameters were calculated. It is found that the relation between I-
      concentration (x) and RTP lifetime (tau) can be expressed as tau = 1.25e(-0.477x)
      and the rate constants of phosphorescence emission k(p) was 0.800 per ms. The
      method was applied directly to determination of propranolol in urine and drug
      tablets with a satisfactory result. The recoveries were 96.6-97.4% and the
      relative standard deviation was 2% for the 1.00 x 10(-6)-4.00 x 10(-6) mol l(-1)
      propranolol in spiked urine sample.

PMID- 12212745
TI  - Synthesis, spectroscopic characterization and EPR studies on electron transfer
      reactions of bis[N-(2,5-di-tert-butylphenyl)salicylaldiminato]copper complexes
      with PPh3.
AB  - New bidentate N-(2,5-di-tert-butylphenyl)salicylaldimines bearing X = H, HO,
      CH3O, Br, NO2, 3,5-di-Br, 3-NO2-5-Br and 5,6-benzo substituents on the
      salicylaldehyde moiety, LxH, and their mononuclear bis[N-(2,5-di-tert
      butylphenyl)salicylaldiminato]copper(II) complexes, Cu(Lx)2, have been prepared
      and investigated by IR, UV-Visible, 1H NMR, ESR spectroscopy, magnetic
      measurements, as well as reactions of Cu(LX)2 with PPh3 were studied. It has been
      found that some complexes with X = HO and CH3O unlike their electron-withdrawing
      and unsubstituted analogues are readily reduced by PPh3 via intramolecular
      electron transfer from ligand to copper(II) to give Cu-stabilized radical
      intermediates. The spectra of the primary radicals interpreted in terms of
      couplings of unpaired electron with (63,65)Cu, 31P, 14N nuclei and aromatic
      protons.

PMID- 12212746
TI  - Determination of the carbonyl groups in native lignin utilizing Fourier transform
      Raman spectroscopy.
AB  - A near-infrared Fourier transform Raman (NIR-FTR) spectroscopic technique was
      utilized to determine the chemical structure of lignin in a woody matrix. In the
      NIR-FTR spectra of coniferaldehyde and coniferyl alcohol, the Raman bands for the
      carbonyl group and the alpha, beta unsaturated bond were detected at 1620 and
      1660 cm(-1), respectively. These peaks were also found in the NIR-FTR spectra of
      chemically synthesized lignins, isolated lignin from conifer wood, and conifer
      wood meal. Upon the reduction of carbonyl groups in the lignin samples and wood
      meal, the band at 1620 cm(-1) disappeared; on the other hand, the band at 1660
      cm(-1) remained unchanged. However, upon the oxidation of reduced lignin at the
      benzyl hydroxyl group using dicyanodichrolobenzoquinone, the band at 1620 cm(-1)
      clearly appeared, strongly suggesting that the band at 1620 cm(-1) can be
      assigned as a carbonyl marker band. The hydrogenation reaction optimized for the
      reduction of the unsaturated bond in lignin caused the disappearance of the band
      at 1660 cm(-1), indicating that the band at 1660 cm(-1) is an alpha, beta
      unsaturated bond marker band. The change in carbonyl content during the wood
      decay process was also shown to be monitored using the Raman intensity of the
      carbonyl marker band. It was indicated that the NIR-FTR spectroscopic techniques
      were suitable analytical method for a rapid and nondestructive analysis of wood
      samples.

PMID- 12212747
TI  - Structure and stability of common sesquiterpenes.
AB  - We present data on the electronic structure, polarity and relative stability of
      14 common sesquiterpenes. The data were obtained by a combination of
      spectroscopic and high-level theoretical analysis. The discussion also includes
      comments on possible implication of molecular properties for physiological
      behaviour.

PMID- 12212748
TI  - Density functional theory studies on the structures and vibrational spectra of
      3,6-dichlorocarbazole and 3,6-dibromocarbazole.
AB  - Becke 3-Lee-Yang-Parr density functional theory (DFT) calculations using 6-311G**
      and 6-311G(2df,p) basis sets were carried out to study molecular structures and
      vibrational spectra of 3,6-dichlorocarbazole and 3,6-dibromocarbazole. The
      optimized geometries, vibrational frequencies, IR intensities, and Raman
      activities have been obtained. On the basis of B3LYP calculations, a normal mode
      analysis was performed to assign the vibrational fundamental frequencies
      according to the potential energy distributions. The computational frequencies
      are in good agreement with the observed results.

PMID- 12212749
TI  - Assignment of the Raman spectra of some deuterated-BEDT-TTF superconductors.
AB  - We present the room-temperature Raman spectra of both the protonated and
      deuterated forms of kappa-(BEDT-TTF)2Cu[N(CN)2]Br, kappa-(BEDT-TTF)2Cu(NCS)2 and
      beta-(BEDT-TTF)2I3. Along with data for the neutral BEDT-TTF molecule these
      spectra are used to assign the many features in the spectra of the deuterated
      compounds.

PMID- 12212750
TI  - Electronic states of 1,6,6a lambda4-trithiapentalene and its 2,5-dimethyl and 2,5
      diphenyl derivatives. Ultraviolet-visible linear dichroism spectroscopy and time
      dependent density functional theory calculations.
AB  - The electronic transitions of 1,6,6a lambda4-trithiapentalene (TTP) and its 2,5
      dimethyl and 2,5-diphenyl derivatives (DMTTP and DPTTP) are investigated by
      ultraviolet-visible linear dichroism spectroscopy on molecular samples partially
      aligned in stretched polyethylene, and by time-dependent density functional
      theory calculations (TD-B3LYP/6-31G*). The theoretical predictions are in good
      agreement with the observed polarization spectra, allowing a detailed assignment
      of observed transitions to calculated electronic states. According to the
      theoretical results, sigma-sigma* excitations involving orbitals associated with
      the unique S-S-S three-center bonding in the TTP ring system play a fundamental
      role in the description of low-lying electronic states. The visible absorption
      band close to 20,000 cm(-1) and the dominant peak in the near-ultraviolet region
      around 39,000 cm(-1) can thus be assigned to transitions with a high degree of
      sigma-sigma* character. The situation is slightly more complicated in the case of
      DPTTP because sterically induced twisting of the phenyl groups leads to mixing of
      pi and sigma orbitals.

PMID- 12212751
TI  - Electron spin resonance investigations of human retinal pigment epithelium
      melanosomes from young and old donors.
AB  - Electron spin resonance (ESR) examinations of human retinal pigment epithelium
      melanosomes isolated from eyes of young and old donors were carried out. The
      examined ESR signal was a single line, which is characteristic for free radicals
      of eumelanin o-semiquinones. The content of free radicals related to melanosomes
      dry weight for samples from older donors (ages over 45 years) were higher than
      for sample from younger donors (between 14 and 22 years). Simultaneously, the
      content of free radicals calculated for one melanosome is constant and does not
      depend on age. The homogeneous broadening of the recorded ESR lines shows that
      there are no isolated spin packets in all investigated melanin samples. Slow spin
      lattice (T1 approximately 10(-5) s) and fast spin-spin (T2 approximately 10(-8)
      s) relaxation processes occur in these samples. Saturation of the ESR lines at
      low microwave power was measured. High concentration of free radicals in
      melanosome samples was responsible for the fast spin-spin relaxation process.

PMID- 12212752
TI  - Diastereotopic effect in some N-substituted-3-methyl-4,1-benzoxazepine-2,5
      diones.
AB  - 1H NMR assignment of seven differently N-substituted-3-methyl-4,1-benzoxazepine
      2,5-diones (I) revealed that with the exception of allyl, N-methylene protons of
      the substituents exhibit diastereotopy due to presence of a chiral centre in the
      heterocyclic ring at C-3. The significant finding is that the methylenes at C-2'
      in the substituents n-propyl and n-butyl (Id, Ie) also show diastereotopy.
      However, the one closer to the chiral centre (at C-1') exhibits greater non
      equivalence of its protons. The diastereotopic methylene groups reported in this
      study correspond to the simplest system AB on one hand and as complex as ABMM'X2
      or ABMM'X3 on the other. Calculated spectra obtained from assigned set of data
      for most of the coupled protons were in good agreement with the observed ones.

PMID- 12212753
TI  - Characterization of alkali treated flax fibres by means of FT Raman spectroscopy
      and environmental scanning electron microscopy.
AB  - Flax fibres grown under well managed conditions were submitted to NaOH chemical
      treatments, so called Mercerization. The extent of the polymorphic transformation
      of cellulose I into cellulose II taking place within the crystalline domains of
      the fibre cellulose was dependent on the alkali concentration. FT Raman
      spectroscopy turned out to represent an ideal tool for detecting the polymorphic
      transformation of the cellulosic fine structure of the flax fibres in vivo. In
      addition to the differences of the FT Raman spectra in the frequency range below
      1500 cm(-1), second derivatives of the spectra in the range of the CH stretching
      vibrations could also be used to distinguish the two polymorphic modifications.
      The intensity ratio R of the stretching modes v(s)COC and v(as)COC represents a
      spectral parameter characterising the molecular structure of the flax fibres. As
      a supplementary tool, Environmental scanning electron microscopy (ESEM) was used
      to visualize the microstructural fibre properties dependent on the alkali
      concentrations during the Mercerization.

PMID- 12212754
TI  - Aroylthioureas: new organic ionophores for heavy metal ion selective electrodes.
      A nuclear magnetic resonance study.
AB  - The 1H and 13C NMR spectra of four series of 1-aroylthiourea derivatives in DMSO
      d6 are reported. The NH signals for 3-alkyl substituted aroylthioureas are
      identified by their multiplicity and by homonuclear irradiation experiments.
      Correlation analyzes are made for NH, CO and CS signals in order to determine the
      best way to modulate the nucleophilic character of the CS group, as thioureas are
      well-known ionophore groups. Almost all 1,3-substituted thioureas (Series 2-4)
      show the reported chelated structure with the exception of those with CF3, CN and
      NO2 groups. Pyridine group promote a different equilibrium in solution. The
      fragment -CO-NH- transmits poorly the electronic effects of substituents in the
      aroylgroup.

PMID- 12212755
TI  - Raman and UV-visible absorption spectra of ion-paired aggregates of copper
      porphyrins.
AB  - Raman and UV-visible absorption spectra of ion-paired aggregate constructed from
      two copper porphyrins, copper tetrakis(4-N-methylpyridyl)porphyrin (CuTMPyP) and
      copper tetrakis(4-sulfonatophenyl)pophyrin (CuTSPP), are reported in this paper.
      The absorption bands of the aggregate was found exhibiting obvious shift and
      broadening, which are attributed to the excitonic coupling between the two paired
      porphyrin rings. The excitonic coupling in the aggregates also induces evident
      alteration for Raman intensities compared with monomer spectrum. Aggregation
      results in only small shifts (2-3 cm(-1)) for Raman lines connecting with the
      vibrations of porphyrin rings, manifesting only slight structural change of
      porphyrin skeletons. On the other hand, evident downshift (5 cm(-1)) was observed
      for the Cm-pyridyl stretch mode (1254 cm(-1)) of CuTMPyP, suggesting weakening of
      the Cm-pyridyl bonds by aggregation. Raman depolarization ratios of the
      aggregates are different from those of the monomers, implying a lowering of
      effective symmetry due to the molecular packing in the aggregates.

PMID- 12212756
TI  - Vibrational frequencies and structure of B4Cl4: an ab intio quantum chemical
      study.
AB  - The normal mode frequencies and corresponding vibrational assignments of B4Cl4
      are examined theoretically using the Gaussian 98 set of quantum chemistry codes.
      All normal modes were successfully assigned to one of three types of motion
      predicted by a group theoretical analysis (B-B stretch, B-Cl stretch, B-Cl bend)
      utilizing the Td symmetry of the molecule. The vibrational modes of the naturally
      isotopically substituted (1-(10)B, 2-(10)B, 3-(10)B and 4-(10)B) forms of B4Cl4
      were also calculated and compared against experimental data. A complex pattern of
      frequency shifts and splittings is revealed.

PMID- 12212757
TI  - The comparative clinical and economic benefits of drugs should be established and
      discussed as part of any formulary decision process.

PMID- 12212758
TI  - The potential of pill splitting to achieve cost savings.
AB  - OBJECTIVES: To present a methodology for identifying specific medications for
      which pill splitting is clinically appropriate and cost saving, to present data
      from a commercial managed care population on current pill-splitting practices,
      and to estimate additional cost savings from extended use of this strategy. STUDY
      DESIGN: Retrospective pharmacy claims analysis. METHODS: Pharmacy claims data
      from a commercial managed care health plan covering 19,000 lives and national
      drug data were used to compile a list of frequently prescribed medications.
      Excluding medications in which packaging, formulation, and potential adverse
      pharmacologic outcomes prohibited splitting, we performed a cost analysis of
      medications amenable to splitting. RESULTS: Eleven medications amenable to pill
      splitting were identified based on potential cost savings and clinical
      appropriateness: clonazepam, doxazosin, atorvastatin, pravastatin, citalopram,
      sertraline, paroxetine, lisinopril, nefazadone, olanzapine, and sildenafil. For
      these medications, pill splitting is currently infrequent, accounting for annual
      savings of $6200 (or $0.03 per member per month), just 2% of the potential
      $259,500 (or $1.14 per member per month) that more comprehensive pill-splitting
      practices could save annually. CONCLUSIONS: Pill splitting can be a cost-saving
      practice when implemented judiciously using drug- and patient-specific criteria
      aimed at clinical safety, although this strategy is used infrequently.

PMID- 12212759
TI  - Rational use of antibiotics to treat respiratory tract infections.
AB  - OBJECTIVES: To foster the appropriate use of antimicrobial agents for respiratory
      tract infections and to review factors that should help achieve this objective.
      STUDY DESIGN: Review of evidence-based guidelines and recommendations for proper
      antibiotic drug use for respiratory tract infections. RESULTS AND CONCLUSIONS:
      Antibiotic drug overuse and inappropriate antibiotic drug selection are
      associated with increased drug resistance among respiratory pathogens (most
      notably, Streptococcus pneumoniae), possible progression to chronic disease, and
      increased treatment costs. Awareness of clinical manifestations that help
      differentiate viral from bacterial infection and the use of guidelines can
      promote the appropriate management of respiratory tract infections. Community
      acquired pneumonia, acute bacterial rhinosinusitis, and selected cases of acute
      exacerbations of chronic bronchitis (50%) warrant antimicrobial therapy, whereas
      otitis media with effusion, acute bronchitis, and most rhinosinusitis are viral
      and do not require antibiotic therapy.

PMID- 12212760
TI  - Reducing cesarean delivery rates in managed care organizations.
AB  - BACKGROUND: A national consensus has emerged that cesarean delivery (CD) rates
      are excessive. OBJECTIVES: To review the subject of CD delivery and to discuss
      options for reducing CD delivery rates in managed care organizations (MCOs) from
      the current rate of approximately 22% to a rate of 10% to 15% in 5 years, as
      proposed by the World Health Organization. STUDY DESIGN AND METHODS: Literature
      review. RESULTS: Contracted physicians could be provided with evidence-based
      clinical practice guidelines for CD as well as data on acuity-adjusted physician
      specific CD rates within the MCO and could be offered supplementary fees for
      performing vaginal deliveries after a previous CD. Administrators and physician
      leaders of contracted hospitals could also be asked to adopt written criteria for
      lack of progress in labor, to review all indications for CD for all cases, to
      encourage use of vaginal delivery after a previous CD, and to require a second
      opinion for performing all except emergency CDs. Members of MCOs who become
      pregnant could be mailed an educational pamphlet that encourages vaginal delivery
      rather than CD. CONCLUSIONS: To facilitate dissemination of information, MCOs
      should report their experience in implementing, monitoring, and evaluating the
      effectiveness and outcomes of programs to reduce CD delivery rates. The MCO
      objective would be to lower CD rates without alienating physicians or attempting
      to impose a regimented approach that would offend and be counterproductive for
      consumers.

PMID- 12212761
TI  - Recombinant human erythropoietin usage in a large academic medical center.
AB  - OBJECTIVE: Recombinant human erythropoeitin (rhEPO) is a highly effective but
      expensive drug used for the treatment of certain anemias. We considered
      opportunities to curtail inpatient rhEPO utilization in light of therapeutic
      alternatives, the drug's delayed onset of action, and the available literature.
      STUDY DESIGN: A retrospective review of rhEPO administration in a large academic
      medical center between February and June 2000 was conducted by using
      administrative databases. METHODS: The computerized inpatient pharmacy
      transaction file of the Hospital of the University of Pennsylvania was queried to
      determine trends for rhEPO administration. We then employed CaduCIS (CareScience,
      Philadelphia, PA) to determine the clinical diagnoses and resources used for each
      inpatient receiving rhEPO. RESULTS: In the study period, 248 inpatients received
      at least 1 rhEPO dose. More than 100 different physicians, representing 20
      departments and divisions, ordered approximately 17 million units of rhEPO.
      Hematology/Oncology accounted for 33% of all units ordered, and Surgery and
      General Medicine ordered 16% and 14%, respectively. The usual length of stay for
      patients receiving rhEPO varied considerably: 34% of patients remained in
      hospital for < or = 7 days, while 31% remained > or = 3 weeks. As many as 34% of
      patients began rhEPO therapy as inpatients. Of inpatients receiving rhEPO, only
      49% met labeled indications for rhEPO administration. CONCLUSIONS: At our
      institution, approximately one half of all inpatient rhEPO usage is for an off
      label indication. Utilization patterns may suggest strategies for conserving this
      scarce resource.

PMID- 12212762
TI  - Coronary artery bypass grafting in octogenarians: clinical and economic outcomes
      at community-based healthcare facilities.
AB  - BACKGROUND: Results of recent studies from high-volume academic centers suggest
      that coronary artery bypass grafting (CABG) is becoming safer to perform in
      octogenarians. Similar data from community-based facilities do not exist.
      OBJECTIVE: To assess the clinical and economic outcomes of nonemergency CABG in
      338 octogenarians at 27 community-based facilities across the United States.
      STUDY DESIGN: Retrospective cohort analysis. PATIENTS AND METHODS: Multivariate
      analyses were used to compare (1) in-hospital mortality rates, (2) rates of
      discharge to extended-care facilities, (3) lengths of stay, and (4) in-hospital
      costs between octogenarians and younger patients. RESULTS: Of 338 patients 80
      years or older, the in-hospital mortality rate was higher (4.7% vs 2.1%; P =
      .002), the rate of discharge to extended-care facilities was greater (24.9% vs
      4.8%; P < .001), the length of stay was longer (9.6 vs 7.9 days; P < .001), and
      in-hospital costs were higher ($20,188 vs $18,196; P < .001) compared with
      patients younger than 80 years. After adjusting for several covariates, we found
      that octogenarians were at significantly greater risk of experiencing in-hospital
      deaths (odds ratio, 4.6; P = .001), of being discharged to extended-care
      facilities (odds ratio, 28.4; P < .001), and of having longer lengths of stay
      (difference, 0.7 days; P = .002) than were patients aged 50 to 59 years.
      CONCLUSION: At these 27 community-based facilities, the in-hospital mortality for
      nonemergency CABG in octogenarians was 4.7%; however, nearly 25% of surviving
      octogenarians were discharged to extended-care facilities.

PMID- 12212763
TI  - Strategies for drug discovery for cognitive aging and Alzheimer's disease.

PMID- 12212764
TI  - Amyloid peptide toxicity and microtubule-stabilizing drugs.
AB  - Based on microtubule (MT) disruption observed in primary neurons exposed to
      fibrillar amyloid peptides (A beta), we tested the potential protective effect of
      MT-stabilizing drugs such as Taxol against A beta-induced disruption of the
      cytoskeleton. Although Taxol was strongly protective, the fact that it does not
      cross the blood brain barrier (BBB) led us to synthesize and test other agents
      with MT-stabilizing properties and possible penetration into the brain. Our
      studies have thus far demonstrated that several MT-stabilizing agents, including
      some with structures quite different from that of Taxol, showed significant
      protective effects. However, not all agents that promoted MT-assembly were
      protective, suggesting additional mechanisms are involved in the actions of the
      drugs. A small number of neuroprotective compounds appear to have potential to
      enter the brain and thus might be tested to see if they slow progression of
      neurodegeneration in an appropriate animal model of Alzheimer's disease.

PMID- 12212765
TI  - Alzheimer's therapeutics: neurotrophin small molecule mimetics.
AB  - A substantial portion of neuronal populations undergoing degeneration in
      Alzheimer's and other neurodegenerative disorders express neurotrophin receptors.
      Neurotrophin small molecule mimetics constitute candidate compounds that might be
      useful in preventing or delaying loss of neuronal function, neural networks or
      neuronal death in neurodegenerative states. We are testing the hypothesis that
      pharmacophores based on a combination of the crystal structures of neurotrophins
      and structure-activity relationships of active neurotrophin peptidomimetics can
      be used to screen small molecule libraries to identify non-peptide small
      molecules with neurotrophin agonist or antagonist activity. In preliminary
      screens using pharmacophores based on two nerve growth factor (NGF) loop domains,
      a number of small molecules have been identified that display neurotrophic
      activity using in vitro bioassays. Current studies are focused on determining
      whether these small molecules function via neurotrophin receptors and whether
      they activate neurotrophin signaling cascades. Assessment of structure-activity
      relationships between active and inactive small molecules will allow modification
      of pharmacophores and provide a basis for the iterative process if identifying
      compounds with increased potency and efficacy. A collection of such compounds
      will provide a basis for synthesis of compounds with targeted pharmacological
      properties.

PMID- 12212767
TI  - Structure-based functional design of chemical ligands for AMPA-subtype glutamate
      receptors.
AB  - Glutamate receptors (GluRs) function as transmembrane ion channels to regulate
      intracellular level of ions such as calcium in control of excitatory synaptic
      transmission of the central nervous system. Dysfunction of these glutamate
      receptors has been implicated in human brain neurodegenerative diseases,
      including Alzheimer's, Huntington's, and Parkinson's diseases. Despite such a
      significant role in both the biology and pathology of the central nervous system,
      detailed understanding of molecular mechanisms by which subtype- or subunit
      specific glutamate receptors function in cells is still lacking. The recently
      determined three-dimensional crystal structure of the extracellular ligand
      binding core of the prototypic AMPA-subtype GluR2, in complex with its agonist,
      provides a new opportunity for rational design of chemical ligands that could
      help elucidate the underlying mechanisms and also be useful in the therapy of the
      neurodegenerative diseases. Here we report our recent development in structure
      based functional design of chemical ligands by using nuclear magnetic resonance
      (NMR) spectroscopy. The NMR structure-based method enables rapid identification
      of small molecular chemical ligands that bind to specific sites of the target
      protein. These chemical compounds can be optimized for selective binding to the
      target protein, and linked to produce chemical ligands with high-affinity and
      selectivity of the AMPA-subtype glutamate receptors.

PMID- 12212766
TI  - Synthesis and evaluation of 2-(3'-iodo-4'-aminophenyl)-6-hydroxybenzothiazole for
      in vivo quantitation of amyloid deposits in Alzheimer's disease.
AB  - A potent and brain permeable amyloid ligand has been identified as a lead
      compound capable of I-123/125-labelling for single photon emission computed
      tomography (SPECT) imaging. In this study, we report the synthesis and I-125
      radiolabelling of Compound 6 and its in vitro and in vivo properties. Compound 6
      [2-(3'-iodo-4'-aminophenyl)-6-hydroxybenzothiazole] bound to synthetic A beta(1
      40) fibrils in a saturable manner, exhibiting an affinity (Ki) of 11+/-1.1 nM in
      a competitive binding assay using a tritiated thioflavin T analog ([3H]BTA-1) as
      radioligand. [125I]6 binding to synthetic A beta(1-40) fibrils fit a single-site
      model. [125I]6 exhibited several-fold higher binding to homogenates of frontal
      cortex from post-mortem Alzheimer's disease brain relative to age-matched control
      brain homogenates. No difference in binding was observed in cerebellum. The ratio
      of radioactivity concentration between frontal cortex and cerebellum was 6-fold
      higher in AD brain homogenates than the age-matched control. [125I]6 also readily
      penetrated the blood-brain barrier in normal control mice with an average
      radioactivity concentration of 6.43+/-0.62%ID/g detected in the whole brain at 2
      min post i.v. injection. At 30 min, the radioactivity concentration decreased to
      0.40+/-0.05%ID/g, indicating good clearance in the absence of amyloid deposits in
      the brain.

PMID- 12212768
TI  - Modulation of axonal regeneration in neurodegenerative disease: focus on Nogo.
AB  - Recent work has demonstrated that axonal regeneration in the central nervous
      system is limited by myelin-derived Nogo binding to an axonal Nogo Receptor. The
      Nogo system appears to have a physiologic role in regulating structural
      plasticity. The possibility that the Nogo system contributes to pathologic and
      compensatory plasticity in Alzheimer's Disease is considered.

PMID- 12212769
TI  - Towards a high-affinity allosteric enhancer at muscarinic M1 receptors.
AB  - Loss of forebrain acetylcholine (ACh) is an early neurochemical lesion in
      Alzheimer's Disease (AD), and muscarinic receptors for ACh are involved in memory
      and cognition, so a muscarinic agonist could provide 'replacement therapy' in
      this disease. Muscarinic receptors, which couple to G-proteins, occur throughout
      the CNS, and in the periphery they mediate the responses of the parasympathetic
      nervous system, so selectivity is crucial. The five subtypes of muscarinic
      receptor, M1-M5, have a distinct regional distribution, with M2 and M3 mediating
      most of the peripheral effects, M2 predominating in hindbrain areas, and M1
      predominating in the cortex and hippocampus--the brain regions most associated
      with memory and cognition, which has lead to a search for a truly M1-selective
      muscarinic agonist. That search has so far been unsuccessful, but
      acetylcholinesterase inhibitors such as donepezil (Aricept), which potentiate
      cholinergic neurotransmission, have a therapeutic role in the management of AD;
      so the M1 receptor remains a therapeutic target. Our approach is to develop
      allosteric enhancers--compounds which bind to the receptor at an 'allosteric'
      site which is distinct from the 'primary' site to which the endogenous ligand
      binds, and which enhance the affinity (or efficacy) of the endogenous ligand. We
      have developed radioligand binding assays and analyses for the detection and
      quantitatitation of allosteric interactions of a test agent with labelled and
      unlabelled 'primary' ligands, and we report here some results of the initial
      phase of a chemical synthesis project to develop potent and selective allosteric
      enhancers at muscarinic M1 receptors.

PMID- 12212770
TI  - Natural product extracts that reduce accumulation of the Alzheimer's amyloid beta
      peptide: selective reduction in A beta42.
AB  - Alzheimer's disease (AD) is the most common form of dementia in the elderly.
      Without a treatment that significantly delays the progression of the disease over
      14 million Americans are likely to be affected with AD by the middle of the 21st
      Century, presenting an enormous economic and social burden. Evidence gathered
      over the last two decades has implicated the abnormal accumulation of A beta, in
      particular the longer more amyloidogenic form A beta42, as a potential causative
      agent in the disease. To screen for compounds that reduce A beta accumulation we
      have established several high throughput, cell based screens capable of the
      sensitive and selective detection of A beta40 and A beta42. Using these screens
      we have analyzed a proprietary library of natural product extracts for their
      ability to influence A beta accumulation. Using this approach, we have identified
      several agents capable of influencing total A beta concentration. In addition, we
      have identified one extract that selectively reduces A beta42.
      Intracerebroventricular administration of this agent to mice results in a
      selective reduction in A beta42 in the brain.

PMID- 12212771
TI  - Calpain inhibitors: a treatment for Alzheimer's disease.
AB  - Activation of the calpain system might contribute to the impairment of synaptic
      transmission in Alzheimer's disease (AD) (Liu et al., 1999; Rapoport, 1999;
      Selkoe, 1994). Calpains regulate the function of many proteins by limited
      proteolysis and initiate the complete degradation of other proteins. In
      particular, they modulate processes that govern the function and metabolism of
      proteins key to the pathogenesis of AD, including tau and amyloid precursor
      protein (APP). (Xie and Johnson, 1998; Wang, 2000). We have found that
      overexpression of APP(K670M:N671L) and PS1(M146L) proteins in hippocampal
      cultures derived from transgenic mice causes an increase in the frequency of
      spontaneous release of neurotransmitter. We have also found that calpain
      immunoreactive clusters are co-localized with immunoreactivity for the vesicle
      associated presynaptic marker, synaptophysin. Moreover, application of calpain
      inhibitor reduces the frequency of spontaneous release of neurotransmitter.
      Therefore, we have hypothesized that calpains might contribute to the increase in
      transmitter release. Based on this hypothesis, we propose to test whether it is
      possible to restore normal synaptic transmission between cells derived from the
      transgenic model of AD by using calpain inhibitors. The transgenic mouse model
      also shows spatial learning impairment, a phenomenon that is thought to be
      associated with plastic changes at synaptic level. Therefore, we will also test
      whether we can rescue the learning impairment through a treatment with calpain
      inhibitors.

PMID- 12212772
TI  - AF150(S) and AF267B: M1 muscarinic agonists as innovative therapies for
      Alzheimer's disease.
AB  - The M1 muscarinic agonists AF102B (Cevimeline, EVOXACTM: prescribed in USA and
      Japan for Sjogren's Syndrome), AF150(S) and AF267B--1) are neurotrophic and
      synergistic with neurotrophins such as nerve growth factor and epidermal growth
      factor; 2) elevate the non-amyloidogenic amyloid precursor protein (alpha-APPs)
      in vitro and decrease beta-amyloid (A beta) levels in vitro and in vivo; and 3)
      inhibit A beta- and oxidative-stress-induced cell death and apoptosis in PC12
      cells transfected with the M1 muscarinic receptor. These effects can be combined
      with the beneficial effects of these compounds on some other major hallmarks of
      Alzheimer's disease (AD) (e.g. tau hyperphosphorylation and paired helical
      filaments [PHF]; and loss of cholinergic function conducive to cognitive
      impairments.) These drugs restored cognitive impairments in several animal models
      for AD, mimicking different aspects of AD, with a high safety margin (e.g.
      AF150[S] >1500 and AF267B >4500). Notably, these compounds show a high
      bioavailability and a remarkable preference for the brain vs. plasma following
      p.o. administration. In mice with small hippocampi, unlike rivastigmine and
      nicotine, AF150(S) and AF267B restored cognitive impairments also on escape
      latency in a Morris water maze paradigm in reversal learning. Furthermore, in
      aged and cognitively impaired microcebes (a natural animal model that mimics AD
      pathology and cognitive impairments), prolonged treatment with AF150(S) restored
      cognitive and behavioral impairments and decreased tau hyperphosphorylation, PHF
      and astrogliosis. Our M1 agonists, alone or in polypharmacy, may present a unique
      therapy in AD due to their beneficial effects on major hallmarks of AD.

PMID- 12212774
TI  - Ovariectomy of young mutant amyloid precursor protein transgenic mice leads to
      increased mortality.
AB  - Alzheimer disease (AD) is a neurodegenerative disease affecting a large
      percentage of the elderly population. Preventative therapies for AD have been
      limited; however, epidemiological studies have demonstrated that estrogen
      replacement therapy may prevent or delay the onset of AD. Therefore, we utilized
      female mutant amyloid precursor protein transgenic mice (APP(SWE)), as a mouse
      model of AD-like pathology, to study the long-term effects of estrogen
      withdrawal. Interestingly, by 8 months of age 58% of the ovariectomized APP(SWE)
      mice had died, whereas there was no mortality in the sham ovariectomized APP(SWE)
      mice. This mortality was correlated with estrogen loss only in the APP(SEW) mice
      since background strain matched ovariectomized wild-type mice had virtually no
      mortality. Cerebral A beta levels in the surviving APP(SWE) ovariectomized
      females were increased by 50% compared to the sham ovariectomized APP(SWE)
      females. However, the levels of A beta in the ovariectomized APP(SWE) mice were
      still well below those observed in 2-year-old APP(SWE) mice that had A beta
      plaques. Therefore, the mildly increased A beta levels were not the suspected
      cause of death in these ovariectomized mice. Previous studies have demonstrated
      increased mortality in mice overexpressing mutant or wildtype APP independent of
      A beta accumulation; thus, estrogen withdrawal may potentiate this phenotype
      associated with APP overexpression.

PMID- 12212773
TI  - Statin therapy for Alzheimer's disease: will it work?
AB  - Disease-modifying therapies are being developed for Alzheimer's disease (AD).
      These are expected to slow the clinical progression of the disease or delay its
      onset. Cerebral accumulation of amyloid beta (A beta) peptides is an early and
      perhaps necessary event for establishing AD pathology. Consequently therapies
      aimed at attenuating brain amyloidosis are expected to be disease modifying.
      Based on the epidemiological evidence pointing to a link between cholesterol
      metabolism and AD and the numerous laboratory studies implicating cholesterol in
      the process of A beta production and accumulation, it is now believed that
      cholesterol-lowering therapies will be of value as disease modifying agents.
      Several epidemiological studies revealed that statin use for the treatment of
      coronary arterial disease is associated with a decreased prevalence or a
      decreased risk of developing AD. These observations require both preclinical and
      clinical validation. The former involves testing statins in one or more animal
      models of AD in order to establish which disease features are affected by statin
      treatment, the relative efficacy with which different statins modify these
      features and the mechanism(s) by which statins affect AD phenotypes. The latter
      requires prospective, randomized, placebo controlled trials to evaluate the
      effect of statin treatment on cognitive and AD biomarker outcomes. We have
      initiated a study aimed at determining the effects of atorvastatin (Lipitor), a
      statin with the largest US market share, on brain A beta deposition in the PSAPP
      transgenic mouse model of Alzheimer's amyloidosis. Our results indicate that
      Lipitor treatment markedly attenuates A beta deposition in this animal model.

PMID- 12212775
TI  - NAP accelerates the performance of normal rats in the water maze.
AB  - NAP (Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln) has neuroprotective, memory enhancing, and
      neurotrophic properties. NAP is a short peptide sequence derived from the
      recently cloned, activity-dependent neuroprotective protein. The current study
      was designed to evaluate NAP activity in normal middle-aged animals to further
      assess NAP's breadth of neuroprotection. NAP was administered by inhalation.
      Results showed that in the paradigm of the Morris water maze, assessing short
      term memory, only the NAP-treated middle-aged rats and not placebo-treated rats
      showed significant improvements by the end of the testing period. These results
      suggest efficacy for NAP in normal aging that is associated with accumulating
      environmental and genetic toxic factors.

PMID- 12212777
TI  - CREB and the discovery of cognitive enhancers.
AB  - In the past few years, a series of molecular-genetic, biochemical, cellular and
      behavioral studies in fruit flies, sea slugs and mice have confirmed a long
      standing notion that long-term memory formation depends on the synthesis of new
      proteins. Experiments focused on the cAMP-responsive transcription factor, CREB,
      have established that neural activity-induced regulation of gene transcription
      promotes a synaptic growth process that strengthens the connections among active
      neurons. This process constitutes a physical basis for the engram--and CREB is a
      "molecular switch" to produce the engram. Helicon Therapeutics has been formed to
      identify drug compounds that enhance memory formation via augmentation of CREB
      biochemistry. Candidate compounds have been identified from a high throughput
      cell-based screen and are being evaluated in animal models of memory formation. A
      gene discovery program also seeks to identify new genes, which function
      downstream of CREB during memory formation, as a source for new drug discoveries
      in the future. Together, these drug and gene discovery efforts promise new class
      of pharmaceutical therapies for the treatment of various forms of cognitive
      dysfunction.

PMID- 12212776
TI  - Brain-imaging surrogate markers for detection and prevention of age-related
      memory loss.
AB  - Recent evidence points to the importance of neuropathological and cognitive
      changes preceding Alzheimer's disease (AD), and clinical trials have begun to
      focus on preventive treatments designed to slow age-related cognitive decline and
      delay the onset of AD in people with age-associated memory impairment (AAMI).
      Studying subjects with few deficits leads to diagnostic heterogeneity and a need
      for larger samples in order to detect active drug effects. In this report, I
      review results of recent studies designed to address such issues. Middle-aged and
      older adults with mild memory complaints were studied using brain imaging and
      measures of the major known genetic risk for AD, the apolipoprotein E-4 (APOE-4)
      allele. In a study of positron emission tomography during mental rest, glucose
      metabolic rates were significantly lower in APOE-4 carriers in brain regions
      affected by AD. Another study using functional magnetic resonance imaging showed
      increased brain activation during memory tasks in APOE-4 carriers in similar
      brain regions. Longitudinal follow-up after 2 yr indicated the potential utility
      of such brain-imaging measures, combined with genetic-risk information, as
      surrogate markers in treatment trials for AAMI to prevent further cognitive
      decline. Current development focuses on novel technologies using positron
      emission tomography to directly image the neuritic plaques and neurofibrillary
      tangles of AD in order to provide more specific measures of disease progression
      in future clinical trials.

PMID- 12212778
TI  - A computer-assisted cognitive test battery for aged monkeys.
AB  - A computer-assisted version of the delayed matching-to-sample (DMTS) task has
      been of enormous utility in our non-human primate model for assessment of memory
      enhancing agents. To avoid ceiling effects as might be encountered by using fixed
      delay intervals in monkeys exhibiting varying performance efficiencies, delay
      intervals are adjusted to provide similar baseline levels of delay-dependent
      performance. Macaques well trained in the task exhibited a marked age-dependent
      sensitivity to the effects of the amnestic drug scopolamine. Aged animals also
      were more affected than their younger counterparts by the presentation of a
      distractor shortly after receiving the stimulus component of the DMTS task. One
      limitation of the DMTS task is that under baseline conditions certain aged
      subjects may perform the task as well or better than some younger animals. To
      help avoid this situation, we developed a titrating version of the DMTS which was
      administered similarly to the standard DMTS task. Animals begin the first trial
      with a 0 s delay interval. Delay intervals after a correct response are
      incremented by 1 s. Delay intervals after an incorrect match are decreased by 1
      s. Rhesus and pigtail macaques who ranged in age from 5-27 years and who were
      maintained on the standard DMTS for at least one year performed 3-4 consecutive
      96 trial sessions. The maximum delay intervals attained by the study group,
      exhibited a significant correlation with age (p < 0.02). Decrements in task
      accuracy, and in the number of trials completed/session showed a trend with age
      (p < 0.08). If the titrating version of the DMTS is sensitive to mnemonic drugs,
      the task may prove useful for drug comparisons with aging.

PMID- 12212780
TI  - Randomized, double-blind, placebo-controlled international clinical trial of the
      Ampakine CX516 in elderly participants with mild cognitive impairment: a progress
      report.
AB  - This progress report briefly describes the rationale and study design for the
      first cross-national clinical study of a positive AMPA-type glutamate receptor
      modulator in subjects with mild cognitive impairment (MCI). The study medication
      for the double-blind, placebo-controlled trial, the AMPAKINE CX516, represents a
      novel pharmacological approach to the treatment of memory disorders. Previous
      preclinical and pilot clinical studies have shown that CX516 has the ability to
      enhance memory and cognition. Design of the trial, including outcome measures and
      inclusion criteria, was aided by an international panel of experts in the newly
      emerging field of MCI.

PMID- 12212779
TI  - The utility of muscarinic agonists in the treatment of Alzheimer's disease.
AB  - Alzheimer's disease is a progressive neurological disorder characterized by
      amyloid plaques and neurofibrillary tangles along with memory and cognitive
      deficits associated with a loss of basal forebrain cholinergic neurons. Efforts
      to treat Alzheimer's disease have focused on compounds that elevate cholinergic
      activity such as cholinesterase inhibitors and direct acting muscarinic and
      nicotinic agonists. Low efficacy and poor selectivity of available compounds have
      limited the clinical utility of muscarinic agonists. Recent studies suggesting a
      role for muscarinic agonists in regulating the production of A beta raise the
      possibility that selective M1 agonists could be useful in treating not only the
      symptoms, but also the underlying cause(s) of Alzheimer's disease. Thus, renewed
      efforts have focused on the development of compounds with improved selectivity
      for M1 receptors and lower toxicity. 5-(3-ethyl-1,2,4-oxadiazol-5-yl)-1,4,5,6
      tetrahydropyrimidine (CDD-0102) is a potent M1 agonist with a low side effect
      profile that enhances memory function in animal models of Alzheimer's disease.
      The available preclinical data suggest that CDD-0102 may be useful in the
      treatment of Alzheimer's disease.

PMID- 12212781
TI  - Slowing the progression of cognitive decline in Alzheimer's disease using
      mifepristone.
AB  - High circulating levels of glucocorticoid hormones adversely affect cognition.
      Previous studies exploring the hypothalamic-pituitary-adrenal (HPA) axis and
      basal cortisol levels in the elderly reported that subjects with mid-range
      cortisol levels outperformed subjects with high cortisol levels on assessments of
      memory and attention. This study examines the efficacy of mifepristone, a
      glucocorticoid-antagonist, in decelerating the rate of cortisol-related cognitive
      decline in subjects with mile-to-moderate Alzheimer's disease (AD). Rate of
      cognitve decline is compared in AD subjects randomized to receive 200 mg of
      mifepristone daily for 6 mo or placebo. The Alzheimer's Disease Assessment Scale
      (ADAS) and the Folstein Mini Mental Status Exam (MMSE) will be the primary
      measures used to assess change in cognitve function over the 6 mo period,
      supplemented by a neuropsychological battery testing memory and language and
      reasoning skills. During each visit, subjects will have samples collected for
      determination of plasma adrenocorticotropin (ACTH), serum cortisol and salivary
      cortisol levels to assess HPA axis activity. The placebo arm of this study also
      investigate whether subjects with high baseline cortisol levels experience
      greater declines in cognitive impairment over time relative to subjects with Ad
      who have low baseline cortisol levels. Additionally, this study test the
      hypothesis that AD subjects with elevated cortisol at baseline will perform more
      poorly on neuropsychological exams that do subjects with low cortisol.

PMID- 12212782
TI  - Nerve growth factor gene therapy for Alzheimer's disease.

PMID- 12212783
TI  - Should the guidelines for monitoring serum cholesterol levels in the elderly be
      re-evaluated?
AB  - Elevated circulating cholesterol can have profound effects on the health of an
      individual. Such excess cholesterol can promote coronary artery disease,
      production and accumulation of beta-amyloid in the brain, and possibly
      Alzheimer's disease (AD). In a clinical trial evaluating the benefit of a
      cholesterol-lowering drug in the treatment of AD, mean cholesterol levels at
      baseline among individuals participating in the trial were found to be relatively
      high. Based on this observation we suggest that cholesterol levels should be
      actively monitored in the elderly, as many individuals with AD are over 65 years
      of age and therefore excluded by currently accepted guidelines.

PMID- 12212784
TI  - Development of indole-3-propionic acid (OXIGON) for Alzheimer's disease.
AB  - The accumulation of amyloid-beta and concomitant oxidative stress are major
      pathogenic events in Alzheimer's disease. Indole-3-propionic acid (IPA, OXIGON)
      is a potent anti-oxidant devoid of pro-oxidant activity. IPA has been
      demonstrated to be an inhibitor of beta-amyloid fibril formation and to be a
      potent neuroprotectant against a variety of oxidotoxins. This review will
      summarize the known properties of IPA and outline the rationale behind its
      selection as a potential disease-modifying therapy for Alzheimer's disease.

PMID- 12212785
TI  - Estrogen and cognitive functioning in men with mild cognitive impairment.
AB  - Although men do not experience an abrupt cessation of gonadal hormone production
      at midlife as do women, levels of testosterone (T) decrease gradually with aging.
      Because estradiol (E2) arises mainly from the conversion of T in men, the
      availability of E2 also decreases with increasing age. In randomized clinical
      trials, E2 replacement therapy has been shown to maintain aspects of cognition in
      postmenopausal women, specifically with regard to verbal memory. The present
      prospective, randomized, cross-over trial is being undertaken in order to
      determine whether E2 will enhance verbal memory in men with Mild Cognitive
      Impairment (MCI). Men with MCI will randomly receive E2 or placebo for the first
      3 mo of treatment and will then be crossed-over to the other treatment for an
      additional 3 mo. A battery of neuropsychological tests will be administered at
      pretreatment and, again, following each 3-mo treatment phase. It is hypothesized
      that elderly men with MCI will perform better on tests of explicit memory when
      they are being treated with E2 compared to their performance under placebo
      conditions.

PMID- 12212786
TI  - Effects of aerobic fitness training on human cortical function: a proposal.
AB  - We briefly review the extant human and animal literature on the influence of
      fitness training on brain, cognition and performance. The animal research
      provides clear support for neurochemical and structural changes in brain with
      fitness training. The human literature suggests reliable but process specific
      changes in cognition with fitness training for young and old adults. We describe
      a research program which examines the influence of aerobic fitness training on
      the functional activity of the human using event-related functional magnetic
      resonance imaging, of humans in fitness interventions.

PMID- 12212787
TI  - Brain MRI hippocampal volume and prediction of clinical status in a mild
      cognitive impairment trial.
AB  - Mild Cognitive Impairment (MCI) is considered a transitional stage in the
      pathogenesis of Alzheimer's disease; however, not all MCI patients progress to
      clinically defined AD or decline at identical rates. Hippocampal atrophy, as
      measured by Magnetic Resonance Imaging (MRI), may be a marker for hippocampal
      pathology in patients with MCI and predict a more rapid deterioration to clinical
      AD. In this study, we used MRI data from an ongoing MCI clinical trial to
      determine whether MRI hippocampal volume at baseline was associated with
      cognitive and functional performance in MCI subjects and whether it predicted
      those individuals who were more likely to develop AD. We performed correlational
      analyses between the MRI hippocampal volumes at study entry and the subjects'
      concurrent performance on neuropsychological measures and clinical ratings.
      Larger hippocampal volume was associated with better performance on tests of
      memory, general cognition, and overall clinical ratings. Further analyses
      suggested that a smaller baseline hippocampal volume may be associated with a
      higher risk of developing clinical AD. As the trial is still ongoing, these
      results require confirmation once the trial is completed. In summary, these data
      suggest that MRI hippocampal volume may be a useful correlate of disease severity
      in MCI subjects and a prognostic indicator of subsequent AD.

PMID- 12212788
TI  - The genetics of exceptional human longevity.
AB  - How we age as individuals is no doubt a complex interaction of genetic and
      environmental factors. Studies of certain populations with optimal environments
      and health-related behaviors, as well as twin studies, suggest that the average
      set of genetic variations should facilitate the average person's ability to live
      to around age 85. Average life expectancies are lower than this because we
      generally fight survival advantage with bad health habits that can lead to
      premature aging, chronic illness, and death at a significantly younger age.
      Centenarians on the other hand live 15-25 years beyond what the average
      collection of us are able to achieve. Many of them have a history of aging
      relatively slowly, and either markedly delaying or even escaping lethal diseases
      associated with aging (Alzheimer's disease, stroke, cancer, cardiovascular
      disease, and diabetes). In order to live to such old age, centenarians are less
      likely to have genetic and environmental exposures that would cause at least
      lethal diseases at younger ages. Demographic selection is the drop out within a
      cohort, of genotypes linked to age-related lethal diseases and premature
      mortality as the cohort achieves older and older age. The result is a very old
      cohort that lacks these genotypes relative to younger age groups. Recent pedigree
      and molecular genetic studies indicate that scientists can use this selection to
      their advantage in discerning genotypes that play important roles in delaying or
      escaping diseases such as Alzheimer's disease, and in slowing the aging process.

PMID- 12212789
TI  - Genetic and environmental risk factors for Alzheimer's disease in Israeli Arabs.
AB  - OBJECTIVE: We studied the genetic and environmental risk factors and prevalence,
      and incidence of dementia of the Alzheimer type (DAT) among the elderly in an
      Arab community in Israel. BACKGROUND: Epidemiological and genetic studies of
      dementia have rarely been reported in an Arab population. METHODS: All persons
      aged 60 years or older who were residents of the rural area of Wadi Ara were
      examined for identification of DAT, vascular dementia (VaD) and conversion from
      age related cognitive decline (ARCD) to DAT using DSM-IV criteria and a semi
      structured questionnaire for collection of demographic and medical data. ApoE
      genotype was also determined. Total plasma homocysteine (tHcy) was determined
      using HPLC with fluorescence detection. Vitamins B12 and plasma folate were
      determined using a commercial radioisotope dilution kit assay (ICN). RESULTS: DAT
      was diagnosed in 20.5% of this population. Its prevalence increased steeply with
      age. Illiteracy was very common, and strongly associated with higher prevalence
      of DAT. The annual incidence of DAT among ARCD cases was 4.4%. Subjects with ARCD
      who developed DAT were older than ARCD subjects who did not develop dementia.
      Hypertension was significantly more common among converted patients than among
      non-converted. Illiteracy was insignificantly more common among those who
      developed DAT than among those who remained ARCD. Vascular dementia (VaD)
      constitutes about 22% of the total dementia population. We also confirm the
      association between VaD, illiteracy and hypertension. Smoking did not represent a
      risk factor for VaD. The survival rates among the three groups (healthy subjects,
      ARCD and DAT) was 80.5%, 58.8% and 55.5% respectively. Homocysteine levels were
      significantly higher than found in studies in Cleveland. Plasma B12 and plasma
      folate levels did not differ significantly between DAT patients and controls
      after adjusting for year of birth. CONCLUSIONS: Our findings suggest that the
      Wadi Ara population is unique because of high prevalence rates of dementia. We
      found old age, female gender and lack of education to be risk factors for the
      development of DAT. The ApoE epsilon4 allele is relatively uncommon in this
      population and it cannot explain the high DAT prevalence. We also confirm the
      association between VaD, illiteracy and hypertension and older age and
      hypertension are risk factors for the transformation of ARCD to DAT.

PMID- 12212790
TI  - Lipid rafts play an important role in A beta biogenesis by regulating the beta
      secretase pathway.
AB  - The Alzheimer's amyloid beta protein (A beta) precursor (APP) is proteolytically
      cleaved by beta-secretase to N- and C-terminal fragments sAPPbeta and CTFbeta,
      respectively. Subsequently, CTFbeta is cleaved by gamma-secretase to generate A
      beta. We previously showed that the levels of secreted A beta and sAPPbeta were
      significantly reduced upon removal of glycosylphosphatidylinositol (GPI)-anchored
      proteins from either primary brain cells or Chinese hamster ovary cultures. The
      results indicated that GPI-anchored proteins facilitated beta-secretase activity.
      In this report, we strengthen the previous findings by demonstrating that
      CTFbeta, like sAPPbeta, is also reduced upon removal of GPI-anchored proteins and
      that sAPPbeta does not accumulate in an intracellular compartment. This
      facilitation pathway does not appear to be important for the processing of a
      disease-linked mutant form of APP (670NL), known to be a superior beta-secretase
      substrate. A novel aspartyl protease, BACE, responsible for beta-secretase
      activity in the brain is not GPI-anchored. However, BACE in brain membranes
      accumulate in lipid rafts, a compartment marked by the accumulation of GPI
      anchored proteins. This finding is consistent with the hypothesis that BACE
      interacts with GPI-anchored proteins that facilitate its activity possibly by
      chaperoning it into lipid rafts.

PMID- 12212791
TI  - The role of the low-density lipoprotein receptor-related protein (LRP1) in
      Alzheimer's A beta generation: development of a cell-based model system.
AB  - The clearance and degradation of extracellular A beta is critical for regulating
      beta-amyloid deposition, a major hallmark of brains of patients with A beta in
      Alzheimer's Disease. The low-density lipoprotein receptor-related protein, LRP1,
      is a large endocytic receptor that significantly contributes to the balance
      between degradation and production of A beta. An extracellular portion of the
      LRP, known as the cluster II region can bind to the secreted form of APP (sAPP
      KPI). We show here that a GST fusion protein containing the cluster II region of
      LRP can be used as a 'mini-receptor' that specifically binds to sAPP-KPI from
      conditioned cultured medium. The binding between the GST-LRP-cluster II fusion
      protein and sAPP-KPI can be inhibited with the strong binding ligand of LRP1,
      called receptor-associated protein (RAP). Furthermore, a cell-based in vitro
      assay system has been developed to monitor the production of total A beta and A
      beta(1-42) in the presence and absence of RAP in Chinese hamster ovary (CHO) cell
      lines both deficient in LRP and expressing LRP. A 3-day treatment of the L2 (CHO
      cells deficient in LRP and overexpressing APP751) and L3 (CHO cells expressing
      LRP and overexpressing APP751) cell lines with RAP showed a decrease in total A
      beta and, interestingly, also a decrease in the ratio of A beta42/A beta(total).
      This cell-based model system and LRP-cluster II mini-receptor will be very useful
      for screening novel compounds that can reduce A beta accumulation by inhibiting
      binding of APP-KPI to LRP1.

PMID- 12212792
TI  - Novel glycosaminoglycan precursors as anti-amyloid agents part II.
AB  - In vivo amyloids consist of two classes of constituents. The first is the disease
      defining protein, e.g., A beta in Alzheimer's disease. The second is a set of
      common structural components that usually are the building blocks of basement
      membrane (BM), a tissue structure that serves as a scaffold onto which cells
      normally adhere. In vitro binding interactions between one of these BM components
      and amyloidogenic proteins rapidly change the conformation of the amyloidogenic
      protein into amyloid fibrils. The offending BM component is a heparan sulfate
      (HS) proteoglycan (HSPG), part of which is protein and the remainder a specific
      linear polysaccharide, which is the portion responsible for binding, and
      imparting the typical amyloid structure, to the amyloid precursor
      protein/peptide. Our past work has demonstrated that agents that inhibit the
      binding between HS and the amyloid precursor are effective anti-amyloid compounds
      both in vitro and in vivo. The present work is concerned with the design and
      synthesis of modified sugar precursors of HS, which, when incorporated into the
      polysaccharide, will alter its structure so that it loses its amyloid precursor
      protein/peptide-binding and fibril-inducing properties. As part of our continuing
      study, since our previous report, 17 additional compounds have been designed and
      synthesized based primarily on the known steps involved in HS biosynthesis. In
      addition to the 4 reported last year, 10 more have been assessed in tissue
      culture for their inhibitory effect on heparan sulfate synthesis, and one of
      these has been assessed for its AA-amyloid inhibitory properties. The majority of
      the novel sugars are analogues of N-acetylglucosamine. They have been modified
      either at the 4-OH, 3-OH, or 2-N positions. The majority of the 2-N analogues
      provide data suggesting that hepatocyte N-demethylases remove the N-substituents
      converting the 2-N analogues into the natural sugar, a process that dilutes the D
      [3H] glucosamine tracer used to track heparan sulfate synthesis and thereby gives
      the impression that biosynthetic inhibition is occurring. To date 3-deoxy
      analogues have failed to affect heparan sulfate synthesis significantly.
      Compounds incorporating the 3,4-dideoxy structural feature are currently being
      assessed. Using primary hepatocyte cultures, we reported previously that a 4
      deoxy analogue is incorporated into HS and terminates its elongation. From the 4
      deoxy series, one of the compounds has now been assessed in an in vivo model of
      AA-amyloid induction. This 4-deoxy analogue inhibited splenic AA amyloid
      deposition by at least 50%, and liver AA amyloid deposition by 85% when measured
      as amyloid/unit area of tissue. Furthermore, the spleen weights of the treated
      group were 1/2-1/3 of that in the untreated group indicating that the total
      splenic amyloid was 1/4-1/6 of that in the untreated group. The results provide
      further evidence that heparan sulfate is a critical factor in amyloidogenesis and
      modifications of sugar precursors of heparan sulfate synthesis may provide leads
      for therapeutic intervention in amyloidogenesis.

PMID- 12212793
TI  - Per-6-substituted beta-cyclodextrin libraries inhibit formation of beta-amyloid
      peptide (A beta)-derived, soluble oligomers.
AB  - Alzheimer's disease is the most common cause of dementia in older individuals
      with compelling evidence favoring neuron dysfunction and death triggered by
      assembled forms of A beta(1-42). While large neurotoxic amyloid fibrils have been
      known for years, recent studies show that soluble protofibril and A beta(1-42)
      derived diffusible ligands (ADDLs) may also be involved in neurotoxicity. In the
      present work, dot-blot immunoassays discriminating ADDLs from monomers were used
      to screen libraries of per-substituted beta-cyclodextrin (beta-CD) derivatives
      for inhibition of ADDLs formation. Libraries were prepared from per-6-iodo-beta
      CD by treatment with various amine nucleophiles. The most active library tested
      (containing >2000 derivatives) was derived from imidazole, N, N
      dimethylethylenediamine and furfurylamine, which at 10 microM total library,
      inhibited ADDLs formation (10 nM A beta(1-42)) over a period of 4 hours. The
      latter was confirmed by a western blot assay showing decreased amounts of the
      initially formed A beta(1-42) tetramer. These preliminary experiments suggest
      that derivatized forms of beta-CD can interfere with the oligomerization process
      of A beta(1-42).

PMID- 12212794
TI  - Novel tricyclic pyrone compounds prevent intracellular APP C99-induced cell
      death.
AB  - Alzheimer's disease (AD) is an age-related neurodegenerative disorder
      characterized by the progressive and global loss of cognitive functions.
      Pathological features include a loss of neurons in vulnerable brain regions and
      the extracellular deposition of abnormal protein aggregates known as amyloid
      plaques. Amyloid-beta protein (A beta is the major component of amyloid plaques
      and is derived from a larger transmembrane glycoprotein, termed amyloid beta
      protein precursor (APP), by proteolysis. The AD research has focused on A beta
      production and metabolism, its extracellular deposition, and its cellular
      toxicity. Recent evidence, however, suggests that A beta as well as the C
      terminal fragments (CTF) of APP can accumulate intraneuronally. The neuronal loss
      and synaptic transmission deficit in AD may therefore depend on intraneuronal
      accumulation of A beta/CTF rather than on extracellular plaque formation.
      Accordingly, we propose that one of the primary targets of therapeutic
      intervention should be intracellular A beta/CTF and its toxic cellular effect. We
      have established a cell-culture model in which the neurons degenerate on
      induction of endogenous expression of A beta/CTF of APP. These cultures have been
      used to test whether tricyclic pyrone (TP) compounds may prevent A beta/CTF
      mediated neuronal death. The results to date have been encouraging. Lead
      compounds will now be selected for their abilities to ameliorate A beta/CTF
      mediated pathology in transgenic mice. Our hope is that these compounds may
      eventually prove beneficial for the prevention and treatment of AD.

PMID- 12212795
TI  - Development of a new treatment for Alzheimer's disease and Parkinson's disease
      using anti-aggregatory beta-synuclein-derived peptides.
AB  - The synaptic protein alpha-synuclein is a major constituent of Lewy bodies (LB),
      pathological neuronal inclusion bodies found in Parkinson's disease (PD),
      Alzheimer's disease (AD), and other neurodegenerative disorders. Owing to data
      from patient brains, it was speculated that an imbalance between alpha-synuclein
      and beta-synuclein might be one of the reasons for formation of LBs and the
      consequent functional deficits. This was supported by the fact that beta
      synuclein is able to prevent abnormal alpha-synuclein aggregation. Transgenic
      mice overexpressing alpha-synuclein display LB-like inclusions in different brain
      regions and motor deficits. To verify if re-establishing a normal relation
      between alpha-synuclein and beta-synuclein is able to prevent the pathology,
      bigenic mice have been created that overexpress both synucleins. Beta-synuclein
      decreased formation of LBs by 40% and prevented functional deficits. This is
      considered as preliminary in vivo proof of antiaggregatory function of beta
      synuclein and its potential as therapeutic substance for treatment of
      neurodegenerative disorders linked with abnormal protein aggregation. Peptide
      libraries have been synthesized to explore the active structures of beta
      synuclein. The first 15 N-terminal amino-acids turned out to be important for the
      antiaggregatory effect. Further smaller beta-synuclein-derived peptides have
      screened for antiaggregatory and neuroprotective potency in different tissue
      culture systems. Preliminary data suggest some of them can be used as leads for
      further drug development.

PMID- 12212796
TI  - Radioiodinated styrylbenzene derivatives as potential SPECT imaging agents for
      amyloid plaque detection in Alzheimer's disease.
AB  - Development of probes for beta-amyloid (A beta) plaques, a critical factor
      associated with Alzheimer's disease (AD), provides important tools for studying
      their role in AD. Previously, we reported [125I]IMSB and [125I]ISB as excellent
      probes for A beta plaque labeling. Despite their exquisite in vitro binding
      characteristics, low brain uptakes (likely due to two ionizable carboxylic acid
      groups) limited their potential as in vivo imaging agents. To improve brain
      penetration, we have successfully prepared a neutral radioiodinated probe
      [125I]3. The improved probe displayed good binding affinity for A beta aggregates
      (Ki = 2.0 +/- 0.2 using A beta40 aggregates). In addition, the brominated
      counterpart displayed fluorescent-staining properties of A beta plaques in
      postmortem AD brain sections similar to BSB, a fluoroscent probe reported
      previously. [125I]3 gave excellent plaque labeling by film autoradiography of AD
      brain sections. Unlike [125I]IMSB (which preferentially detects A beta40
      plaques), the improved radioioinated probe, [125I]3, can readily detect plaques
      containing aggregates of both A beta40 and A beta42. The initial brain uptake of
      [125I]3 in normal mice at 2 min p.i. was moderate (0.18% ID) and displayed a very
      slow washout from the brain (0.11%.ID at 4 h p.i). Taken together, these data
      suggest that [125I]3 is useful for in vitro plaque detection, it may not be
      suitable for in vivo monitoring of A beta progression and deposition.

PMID- 12212797
TI  - Using peptide nucleic acids as gene-expression modifiers to reduce beta-amyloid
      levels.
AB  - The deposition of amyloid beta peptide (A beta) is an early and critical aspect
      of Alzheimer's disease. A beta is formed by the cleavage of amyloid precursor
      protein (APP). Studies of familial forms of Alzheimer's disease indicate that
      elevated secretion of A beta, particularly A beta(1-42), is likely to be an
      etiologic agent in the disease. A beta(1-42) is known to cause fibril formation
      and at elevated levels increases aggregation, which can lead to neuronal death.
      It has, therefore, been hypothesized that if the levels of A betaB, particularly
      A beta(1-42), could be reduced that onset of Alzheimer's disease could be slowed
      or possibly prevented. We, therefore, propose using PNAs targeted to APP to
      decrease plasma and brain levels of A beta(1-40) and A beta(1-42). This research
      project is designed to expand upon the discovery in our laboratory that systemic
      administration of antisense or antigene treatments utilizing peptide nucleic
      acids (PNAs) can be used to target and shut down proteins. Antisense strategies
      are methods of specifically targeting a particular protein by inhibiting
      translation by complementary binding to mRNA, while antigene methods inhibit
      transcription by complementary binding to DNA. For experiments involving
      antisense strategies, there are several advantages to using PNAs as opposed to
      the traditional oligonucleotide approaches. We initially preformed our studies in
      rats and identified a PNA sequence that was able to significantly reduce the
      levels of A beta(1-41) in rat brain compared to vehicle control rats. We have
      switched to mice so that we can prepare to perform our experiments in a
      transgenic animal model of Alzheimer's disease. We have, however, run into
      several technical difficulties with using mice compared to rats. In spite of
      this, we have identified one PNA sequence that specifically lowers mouse brain A
      beta(1-40) A beta(1-42) by 37% and 47%, respectively.

PMID- 12212798
TI  - Alzheimer's disease drug discovery targeted to the APP mRNA 5'untranslated
      region.
AB  - We performed a screen for drugs that specifically interact with the 5'
      untranslated region of the mRNA coding for the Alzheimer's Amyloid Precursor
      Protein (APP). Using a transfection based assay, in which APP 5'UTR sequences
      drive the translation of a downstream luciferase reporter gene, we have been
      screening for new therapeutic compounds that already have FDA approval and are
      pharmacologically and clinically well-characterized. Several classes of FDA-pre
      approved drugs (16 hits) reduced APP 5'UTR-directed luciferase expression (> 95%
      inhibition of translation). The classes of drugs include known blockers of
      receptor ligand interactions, bacterial antibiotics, drugs involved in lipid
      metabolism, and metal chelators. These APP 5'UTR directed drugs exemplify a new
      strategy to identify RNA-directed agents to lower APP translation and A beta
      peptide output for Alzheimer's disease therapeutics.

PMID- 12212799
TI  - Continuing strategies for inhibiting Alzheimer's gamma-secretase.
AB  - Gamma-secretase processing of the amyloid-beta precursor protein (APP) releases
      the amyloid-beta peptide, which is widely held to be involved in the pathogenesis
      of Alzheimer's disease. This protease is apparently a complex of integral
      membrane proteins that includes the multi-pass presenilin. Transition-state
      analogue inhibitors of gamma-secretase are important molecular probes of the
      enzyme active site. We have identified new transition-state analogues,
      (hydroxyethy) urea peptidomimetics, that inhibit gamma-secretase activity at
      submicromolar concentrations in cell culture. The inhibitory activity of a family
      of such compounds provided further support that gamma-secretase has loose
      sequence specificity at the active site, and one of these compounds allowed
      partial purification of the protease complex. In addition, because the site of
      gamma-secretase cleavage of APP lies within its single transmembrane domain, we
      designed short peptides based on this domain which assume a helical conformation.
      These peptides inhibited gamma-secretase in the low micromolar range in cell
      culture, suggesting that they indeed mimick the APP substrate conformation.

PMID- 12212800
TI  - Discovery of new chemical classes of synthetic ligands that suppress
      neuroinflammatory responses.
AB  - We used a chemical genomics approach that includes follow up in parallel
      syntheses to discover a new class of compounds that selectively suppress glial
      activation. While the mechanism of action remains to be determined, available
      data and the experimental approach for discovery indicate that the mechanism
      includes inhibition of gene regulating protein kinases. Specifically, the
      increased production of IL-1beta and iNOS in response to various activating
      stimuli, including Abeta1-42, is suppressed while the production of potentially
      beneficial responses, such as ApoE production, is not inhibited. The increased
      production of COX-2 and p38 MAPK activation are also not altered, demonstrating
      the novel nature of potential therapeutic targets compared to currently available
      drugs. The chemical scaffold is 3-aminopyridazine (3-AP). This is an attractive
      scaffold because of its potential for diversification by established, facile
      chemistries and the prior use of a 3-AP scaffold in other central nervous system
      targeted therapeutics. Therefore, the potential bioavailability of 3-AP
      derivatives and the demonstrated cellular selectivity demand that future research
      address the potential efficacy of selective 3-AP derivatives in animal models of
      disease.

PMID- 12212802
TI  - Spatial organization and conformational peculiarities of the callatostatin family
      of neuropeptides.
AB  - The structures and conformational peculiarities of five members of the
      callatostatin family of neuropeptides, i.e. Leu- and Met-callatostatins, ranging
      in size from 8 to 16 amino acid residues have been investigated by a theoretical
      conformational analysis method. A comparative analysis of the conformational
      flexibilities of Met-callatostatin with those of the hydroxylated analogues,
      [Hyp2]- and [Hyp3]-Met-callatostatin has been carried out. Helically packed C
      terminal pentapeptide in the structure of all investigated Leu-callatostatins are
      shown to be possible. The reason for the great number low-energy conformers for
      the callatostatin N-terminus is discussed.

PMID- 12212801
TI  - Significance and mechanism of Alzheimer neurofibrillary degeneration and
      therapeutic targets to inhibit this lesion.
AB  - Abnormally hyperphosphorylated tau which is the major protein subunit of paired
      helical filaments (PHF)/neurofibrillary tangles is the pivotal lesion in
      Alzheimer disease (AD) and related tauopathies. The cosegregation of tau
      mutations with disease in inherited cases of frontotemporal dementia has
      confirmed that abnormalities in this protein can be a primary cause of
      neurodegeneration. Unlike normal tau that promotes assembly and maintains the
      structure of microtubules, the abnormally hyperphosphorylated protein sequesters
      normal tau, MAP1 and MAP2 and consequently disassembles microtubules. The
      abnormal hyperphosphorylation also promotes the self assembly of tau into tangles
      of PHF. The hyperphosphorylation of tau in AD is probably due to a protein
      phosphorylation/dephosphorylation imbalance produced by a decrease in the
      activity of protein phosphatase (PP)-2A and increase in the activities of tau
      kinases which are directly or indirectly regulated by PP-2A. Two of the most
      promising pharmacologic therapeutic approaches to AD are (1) the development of
      drugs that can inhibit the sequestration of normal MAPs by the abnormally
      hyperphosphorylated tau, and (2) the development of drugs that can reverse the
      abnormal hyperphosphorylation of tau by correcting the protein
      phosphorylation/dephosphorylation imbalance.

PMID- 12212803
TI  - Mass spectrometric and chemical stability of the Asp-Pro bond in herpes simplex
      virus epitope peptides compared with X-Pro bonds of related sequences.
AB  - The mass spectrometric analysis of the immunodominant epitope region (273-284) of
      herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) showed a favoured fission
      at the Asp-Pro peptide bond. The fast atom bombardment collision induced
      dissociation (FAB-CID) study of closely related X-Pro peptides documented that
      neither the length nor the amino acid composition of the peptide has a
      significant influence on this preferential cleavage. At the same time the DP bond
      proved to be sensitive to acidic conditions in the course of peptide synthesis.
      These observations prompted us to compare the chemical and mass spectrometric
      stability of a new set of nonapeptides related to the 273-284 epitope region of
      gD, i.e. SALLEDPVG and SALLEXPVG peptides, where X = A, K, I, S, F, E or D,
      respectively. The chemical stability of these peptides during acidic hydrolysis
      was investigated by electrospray ionization mass spectrometry (ESI-MS) and the
      products were identified by ESI-MS and on-line high performance liquid
      chromatography-mass spectrometry (HPLC-MS). The mass spectrometric fragmentation
      and bond stability of the untreated peptide samples were also studied using ESI
      MS and liquid secondary ion mass spectrometry (LSIMS). Both the chemical
      hydrolysis and the mass spectrometric fragmentation showed that the Asp-Pro bond
      could easily be cleaved, while the KP bond proved to be stable under both
      circumstances. On the other hand, the XP bond (X = A, I, S, F or E) fragmented
      easily under the mass spectrometric conditions, but was not sensitive to the
      acidolysis.

PMID- 12212804
TI  - Synthesis and biological properties of the seven alanine-modified analogues of
      the marine cyclopeptide hymenamide C.
AB  - The synthesis and biological activity of the marine cyclopeptide hymenamide C(1),
      showing an inhibitory effect on human neutrophil elastase degranulation release,
      were recently described. Based on this result, it was decided to undertake a
      systematic structure-activity relationship study of this cyclopeptide, based on
      the Ala-scan technique, in order to obtain useful information for the rational
      design of additional analogues. The synthesis and characterization of the seven
      Ala modified analogues are reported and their biological and pharmacological
      properties are described.

PMID- 12212805
TI  - Studies on the synthesis of cyclic pentapeptides as LHRH antagonists and the
      factors that influence cyclization yield.
AB  - Six cyclic pentapeptides containing two or three non-protein amino acids have
      been synthesized by cyclization of linear precursors in dilute solution and
      characterized by TLC. HPLC, NMR, melting point. specific rotation etc. A total of
      72 cyclization reactions were carried out to study the factors that influence
      head-to-tail cyclization: linear precursor sequence, coupling reagent, residue
      configuration, the proportion of DMAP additive, concentration, reaction
      temperature and reaction time. The cyclic pentapeptides will be modified by
      active moieties and evaluated as LHRH antagonists.

PMID- 12212806
TI  - Antimicrobial activity of short arginine- and tryptophan-rich peptides.
AB  - Highly antimicrobial active arginine- and tryptophan-rich peptides were
      synthesized ranging in size from 11 to five amino acid residues in order to
      elucidate the main structural requirement for such short antimicrobial peptides.
      The amino acid sequences of the peptides were based on previous studies of longer
      bovine and murine lactoferricin derivatives. Most of the peptides showed strong
      inhibitory action against the Gram-negative bacteria Escherichia coli and
      Pseudomonas aeruginosa, and the Gram-positive bacterium Staphylococcus aureus.
      For the most active derivatives, the minimal inhibitory concentration values
      observed for the Gram-negative bacteria were 5 microg/ml (3.5 microM), whereas it
      was 2.5 microg/ml (1.5 microM) for the Gram-positive bacterium. It was essential
      for the antimicrobial activity that the peptides contained a minimum of three
      tryptophan and three arginine residues, and carried a free N-terminal amino group
      and an amidated C-terminal end. Furthermore, a minimum sequence size of seven
      amino acid residues was required for a high antimicrobial activity against
      Pseudomonas aeruginosa. The insertion of additional arginine and tryptophan
      residues into the peptides resulted only in small variations in the antimicrobial
      activity, whereas replacement of a tryptophan residue with tyrosine in the hepta-
      and hexapeptides resulted in reduced antimicrobial activity, especially against
      the Gram-negative bacteria. The peptides were non-haemolytic, making them highly
      potent as prospective antibiotic agents.

PMID- 12212807
TI  - Antiproliferative action of valorphin in cell cultures.
AB  - The antiproliferative effects of the haemoglobin beta-chain fragment (33-39)
      (valorphin or VV-haemorphin-5) were studied in a panel of tumour cell lines and
      normal cells of different origin, using various methods of activity determination
      (trypan blue inclusion test, sulphorhodamine B staining, MTT staining, flow
      cytometry and clonogenic test). Valorphin suppressed the proliferation of tumour
      cells by 25%-95%, depending on the cell line. The maximal valorphin activity was
      detected in transformed cells of fibroblastic (L929) and epithelial (MCF-7)
      origin, transformed haematopoietic cells (K562, HL-60) being less sensitive. In
      normal cells, valorphin activity was several fold lower (10%-15%). A study of the
      dynamics of cell proliferation in L929 cells using a visual cell count and flow
      cytometry showed that valorphin induced reversible and relatively short (24 h) S
      phase arrest of cell proliferation, accompanied by a reversible increase of cell
      size. The proliferation delay was followed by a comparatively long period of
      reversible resistance of the cells to the peptide (96 h) when the cells are
      dividing at normal rate. The same dynamics were demonstrated for A549, MCF-7 and
      primary murine breast carcinoma cells. On the basis of the data obtained, a
      pattern of regulation of cell growth by valorphin is suggested.

PMID- 12212808
TI  - HP (2-20) derived from the amino terminal region of helicobacterpylori ribosomal
      protein L1 exerts its antifungal effects by damaging the plasma membranes of
      Candida albicans.
AB  - The fungicidal effects of the peptide HP (2-20). derived from the N-terminal
      sequence of Helicobacter pylori ribosomal protein L1 (RPL1). have been
      investigated. HP (2-20) displays a strong fungicidal activity against various
      fungi, without haemolytic activity against human erythrocyte cells, and the
      fungicidal activity is inhibited by Ca2+ and Mg2+ ions. In order to investigate
      the fungicidal mechanism(s) of HP (2-20). the amount of intracellular trehalose
      was measured in C. albicans. It was found that the amounts of intracellular
      trehalose were decreased when HP (2-20) was used. The action of the peptide
      against fungal cell membranes was further examined by the potassium-release test;
      HP (2-20) was found to increase the amount of K+ released from the cells.
      Furthermore, HP (2-20) caused significant morphological changes, as shown by
      scanning electron microscopy, and by testing the membrane disrupting activity
      using liposomes (phosphatidyl choline/cholesterol; 10: 1, w/w). Our results
      suggest that HP (2-20) may exert its antifungal activity by disrupting the
      structure of cell membranes, via pore formation or direct interaction with the
      lipid bilayers.

PMID- 12212809
TI  - Systematic optimization of a lead-structure identities for a selective short
      peptide agonist for the human orphan receptor BRS-3.
AB  - The orphan receptor, human bombesin receptor subtype 3 (BRS-3) was assigned to
      the G-protein coupled bombesin receptor family because of its high sequence
      homology with the neuromedin B receptor (NMB-R) and gastrin-releasing peptide
      receptor (GRP-R). Since its pharmacology is stiIl unknown, new highly potent and
      selective tool-substances are needed, that may be able to elucidate its possible
      role in obesity and cancer. We have performed structure activity relationship
      studies on the high affinity peptide agonists [D-Phe6,beta-Ala11,Phe13,Nle14]Bn(6
      14) and [D-Phe6,Phe13]Bn(6-13)propylamide, using their ability to mobilize
      intracellular calcium in BRS-3 transfected CHOGa-16 cells combined with receptor
      binding studies. It was demonstrated that for [D-Phe,beta-Ala11,Phe13,Nle14]Bn(6
      14) the side chains of the residues Trp8 and Phe13, and to a smaller extent beta
      Ala11, are the important amino acid side chains for receptor activation and
      binding, however for [D-Phe6,Phe13]Bn(6-13) propylamide His12 seems to be more
      important than Phe13. C-and N-terminal deletions and amino acid substitutions
      allowed further understanding. It was demonstrated that substitution of His 12 by
      Tyr leads to a high selectivity towards GRP-R. Using the acquired information, a
      small tetrapeptide library was designed with compounds presenting Trp and Phe at
      varying stereochemistry and distances, which led to the discovery of the lead
      structure H-D-Phe-Gln-D-Trp-Phe-NH2. Systematic SAR revealed the important
      structural features of this peptide, C-terminal optimization resulted in the
      highly active and selective BRS-3 agonist H-D-Phe-Gln-D-Trp-1-(2
      phenylethyl)amide. In summary, the size of the peptide was reduced from 8 or 9
      amino acids to a tripeptide for BRS-3.

PMID- 12212810
TI  - Conformational analysis of the Galpha(s) protein C-terminal region.
AB  - The C-terminal domain of the heterotrimeric G protein a-subunits plays a key role
      in selective activation of G proteins by their cognate receptors. Several C
      terminal fragments of Galpha(s) (from 11 to 21 residues) were recently
      synthesized. The ability of these peptides to stimulate agonist binding was found
      to be related to their size. Galpha(s)(380-394) is a 15-mer peptide of
      intermediate length among those synthesized and tested that displays a biological
      activity surprisingly weak compared with that of the corresponding 21-mer
      peptide, shown to be the most active. In the present investigation, Galpha(s)(380
      394) was subjected to a conformational NMR analysis in a fluorinated isotropic
      environment. An NMR structure, calculated on the basis of the data derived from
      conventional 1D and 2D homonuclear experiments, shows that the C-terminal
      residues of Galpha(s)(380-394) are involved in a helical arrangement whose length
      is comparable to that of the most active 21 -mer peptide. A comparative
      structural refinement of the NMR structures of Galpha(s)(380-394) and
      Galpha(s)(374-394)C379A was performed using molecular dynamics calculations. The
      results give structural elements to interpret the role played by both the
      backbone conformation and the side chain arrangement in determining the activity
      of the G protein C-terminal fragments. The orientation of the side chains allows
      the peptides to assume contacts crucial for the G protein/receptor interaction.
      In the 15-mer peptide the lack as well as the disorder of some N-terminal
      residues could explain the low biological activity observed.

PMID- 12212811
TI  - The effect of drying dental unit waterline biofilms on the bacterial load of
      dental unit water.
AB  - AIM: To evaluate drying of the dental unit waterlines (DUWL) as a new method of
      controlling the bacterial biofilm therein and thereby to reduce the number of
      living bacteria in dental unit water. SETTING: 18 dental units were incorporated
      into the study. Six units constituted the experimental units, which were emptied
      for stagnant water in the DUWL every night; six units were chlorinated every
      night (positive controls), and six units were left untreated (negative controls).
      OUTCOME MEASURE: Water samples from the ultrasonic scaler were examined
      microbiologically according to the guidelines from the Danish Standard
      Association and the number of colony forming units (cfu) per ml of water was
      determined. RESULT: Drying of DUWL did not reduce the number of cfu per ml in
      dental unit water below the levels found in DUWL left untreated. CONCLUSION: The
      drying of the waterlines for about 16 hours per day during a 19-day period did
      not result in reduced counts of bacteria in water samples from the experimental
      units.

PMID- 12212812
TI  - Periodontal condition and treatment needs (CPITN) in the Bulgarian population
      aged over 60 years.
AB  - AIM: To investigate the periodontal condition and treatment needs of elderly
      people in Bulgaria. SUBJECTS: 653 subjects over 60 years of age (263 males and
      390 females). METHOD: The study was carried out in 1999 using WHO recommended
      survey techniques. The analysis included only the results of the subjects
      eligible for assessment using CPITN, 497 subjects (206 males and 291 females).
      RESULTS: More than 88% of the subjects were affected by periodontal disease of
      various severity. The percentage of subjects with pathological pockets (CPITN 3,
      4) increased with age. CONCLUSIONS: In comparison to the large needs of
      periodontal therapy in general, the complex treatment needs (TN 3) were
      relatively small. The major volume of needs related to periodontal care lie
      within the competence of the general dental practitioner to treat.

PMID- 12212813
TI  - Fee-paying systems and service patterns in a Hong Kong dental clinic.
AB  - OBJECTIVE: This study aimed to describe and compare patients' consumption of
      dental services and dentists' productivity in a university campus clinic before
      and after changing from a time-based to an item-based fee-paying system. METHOD:
      Data were collected from the University of Hong Kong dental clinic which serves
      all university students and staff. A time-based fee-paying system had been in use
      up to February 1999 when it was switched to an item-based system. Computerised
      records of all patients in two 1-year periods starting from February 1996 and
      February 1999 were analysed. RESULTS: The percentages of eligible users who
      attended the University dental clinic were similar in the two study periods (30%
      in 96/97 vs 29% in 99/00). However, on average, patients consumed more dental
      service items in a year after the switch in fee-paying system (3.2 vs 4.1). There
      was also an increase in the mean number of dental service items provided by a
      dentist per working week after the change in fee-paying system (71.5 vs 99.4).
      CONCLUSION: On switching from a time-based to an item-based fee-paying system,
      dentists in the UHS dental clinic became more productive and the consumption of
      dental services per patient also increased.

PMID- 12212814
TI  - The prevalence, aetiology and clinical appearance of tooth wear: the Nigerian
      experience.
AB  - OBJECTIVE: To establish the prevalence and severity of tooth wear among Nigerians
      and to compare the pattern and aetiology with findings of earlier studies in
      Western populations. DESIGN: Clinical examinations for tooth wear using the tooth
      wear index (TWI). SETTING: The Federal Republic of Nigeria. PARTICIPANTS:
      Patients attending the Dental Hospital, Obafemi Awolowo University Teaching
      Hospital's Complex Ile-Ife. OUTCOME MEASURES: Attrition, abrasion and erosion.
      RESULTS: Of the 126 patients with tooth wear 81 had attrition, 20 had abrasion, 9
      had erosion and 16 had attrition and abrasion combined. A total of 15,480 tooth
      surfaces were examined. 2,229 (14.4%) surfaces had tooth wear out of which 1,007
      (6.5%) were pathologically worn down. The frequency of tooth wear increased with
      the age of patients. Most of the pathologically worn surfaces were just one point
      above maximum acceptable value. CONCLUSIONS: The aetiological factors associated
      with tooth wear are not different from those encountered in Western cultures but
      the pattern of wear differs. Pathological tooth wear presents as an age related
      phenomenon and is probably more severe in Nigerians.

PMID- 12212815
TI  - Oral Candida and nasal Aspergillus flora in a group of Saudi healthy dentate
      subjects.
AB  - The prevalence of oral candidal carriage is widely variable in different
      populations but has never been studied previously in a Saudi population. Nasal
      mycological flora has never been investigated previously in a healthy population.
      OBJECTIVES: To assess the oral and nasal candidal and Aspergillus flora in a
      group of Saudi healthy adult dentate subjects. DESIGN: The concentrated oral
      rinse technique and nasal swab technique were used to sample the oral and nasal
      cavity respectively. RESULTS: Candida species were isolated from the oral cavity
      of 52 (52%) subjects. Candida albicans constituted 80.8% of the isolates,
      followed by C. krusei (5.8%). Aspergillus species were isolated from the nose of
      21 (21%) subjects. A. flavus constituted 42.3% of the isolates followed by A.
      niger (31.8%) and A. fumigatus (26.9%). Subjects who did not brush their teeth
      had a significantly higher rate of oral Candida and nasal Aspergillus compared
      with those who brushed regularly (P = 0.02). CONCLUSION: Oral mycological flora
      in the Saudi population is not different than reported for other populations.
      Lack of oral hygiene increases oral candidal colonisation. Larger scale studies
      are encouraged to determine the prevalence of oral candidal carriage in the
      population generally, and the significance of nasal Aspergillus carriage should
      be determined.

PMID- 12212816
TI  - Oral health status of peri-urban schoolchildren in Accra, Ghana.
AB  - AIM: To update and add to the sparse information available on the dental disease
      experience of Ghanaian children. METHOD: A cross-sectional survey where all 4-16
      year-old schoolchildren in a peri-urban community of Accra, Ghana, were examined.
      Three primary schools had been selected by the school authorities for the study.
      RESULTS: Plaque scores ranged from 78.9% in the 4-5-year-olds to a high of 97% in
      the 6-year-olds with the older age groups occupying intermediate levels. The
      proportion with calculus ranged from a low of 40% in the 4-5-year-olds to a high
      of 67% in the 13-16-year-olds. Gingival disease increased with age from slight to
      low in the lower age groups and increasing significantly from 12 years to 16
      years. Caries experience was low to very low from a high of a DMFT score of 1.11
      (SE 0.07 ) in the 7-9-year-olds to a low of 0.30 (SE 0.06 ) in the 13-16-year
      olds. CONCLUSION: Sustained community preventive dental activity needs to be
      instituted in both rural and urban regions to prevent and control both caries and
      periodontal diseases and to prevent future increases in the caries rates as has
      been experienced in some developing countries.

PMID- 12212818
TI  - A map of natural fluoride in drinking water in Pakistan.
AB  - AIM: The assessment of fluoride levels in domestic water supplies in Pakistan.
      METHOD: Water samples were collected from sources supplying the majority of the
      population: taps in places where piped water supply was available, tube-wells,
      boreholes and wells in rural areas, and stream water where appropriate. RESULTS:
      Analysis of 987 water supplies showed that they are predominantly low in fluoride
      content, 84% containing less than 0.7ppm of fluoride. CONCLUSION: For the
      majority of the population in Pakistan there is a clear indication for use of
      alternate sources of fluoride to ensure optimal intake necessary for the control
      of dental caries.

PMID- 12212817
TI  - The second national survey of oral health status of children and adults in China.
AB  - OBJECTIVES: To describe the oral health status of Chinese children and adults at
      national level in relation to location and province and to highlight changes in
      dental caries experience. DESIGN: Cross-sectional study, oral epidemiological
      survey based on WHO methodology, clinical examinations. SETTING: National survey
      by National Committee for Oral Health. SUBJECTS: Representative samples of
      provinces, districts, townships; cluster sampling including subjects aged
      5,12,15,18, 35-44 and 65-74. Each age group consisted of 23,452 participants,
      i.e. total of 140,712 individuals. RESULTS: At age 5, 76.6% were affected by
      dental caries and mean dmft was 4.5. Mean DMFT varied from 1.0 in 12-year-olds,
      1.4 in 15-year-olds, 1.6 in 18-year-olds, 2.1 in 35-44-year-olds to 12.4 in 65-74
      year-olds. In adults, caries experience was higher in females than in males. The
      effect of urbanisation on caries prevalence in children varied by province and
      age. Among adolescents and young adults caries levels were high in urban areas
      while caries experience was high for old-age people of rural areas. At national
      level, changes in dental caries prevalence of 12- and 15-year-olds were small.
      However, some provinces with extensive oral health programmes (e.g. Love Teeth
      Day) showed declining caries experience whereas provinces with limited preventive
      activities had increasing levels of caries. For all age groups, gingival bleeding
      and calculus were most frequent. Severe periodontal conditions were relatively
      rare. CONCLUSION: The systematic implementation of preventive oral care and
      community-oriented health programmes are needed for the continuous promotion of
      oral health in China.

PMID- 12212819
TI  - Immediate or transitional complete dentures: gerodontic considerations.
AB  - Ageing society is a worldwide phenomenon, especially in western countries, were
      the proportion of the aged population reaches about 20%. Of this group about 50%
      constitute what is termed the old-old frail persons who suffer drastic
      physiological changes which exacerbate difficulties in classic dental and
      prosthetic treatments. Epidemiological surveys point out that many of the elderly
      present with about 12-14 teeth with bad periodontal conditions that should be
      extracted. As a result, special strategies have to be elaborated to give an
      appropriate solution to specific medical and prosthetic conditions. Transitional
      procedures are necessary to assure the smooth change between removable partial
      dentures and complete dentures. Even when implant supported dentures are planed
      this transition period is necessary. Clinical decision making is crucial to avoid
      stress to these medically compromised patients.

PMID- 12212820
TI  - Transforming growth factor-beta1 (TGF-beta1): a potential recovery signal in the
      post-ischemic kidney.
AB  - TGF-beta1 has been demonstrated to be up-regulated in response to ischemic events
      both in animal models and in man. Demonstration of this up-regulation in the
      kidney following experimentally induced acute renal failure and in renal
      transplants complements similar findings in coronary and cerebral ischemia.
      Activation of TGF-beta1 occurs as a direct consequence of hypoxia, angiotensin II
      signaling and loss of extra cellular matrix (ECM) integrity, all of which occur
      in renal ischemia-reperfusion injury. TGF-beta1 thus up-regulates the synthesis
      of extracellular matrix components such as fibronectin and collagen IV providing
      a basis for the restoration of epithelial coverage in the regenerating tubule.
      TGF-beta1 also regulates epithelial tubular cell proliferation and
      differentiation. This response is quickly closed down in response to recovery of
      the kidney. This review examines the evidence linking TGF-beta1 activity to
      recovery from renal ischemia thereby constructing a hypothesis for the beneficial
      role of TGF-beta1 in the post ischemic kidney.

PMID- 12212821
TI  - Lipid peroxidation in vitamin E-deficient rats submitted to subtotal nephrectomy.
AB  - Clinical and experimental evidence has indicated that chronic renal failure (CRF)
      is related to increased free radical production. CRF patients show increased
      lipid peroxidation after a progressive reduction in vitamin E, one of the most
      important antioxidants. In the present study the role of vitamin E deficiency in
      lipid peroxidation was investigated in rats submitted to subtotal nephrectomy.
      Male Wistar rats were divided into groups receiving different diets for a period
      of 45 days: SND - sham rats submitted to a regular diet containing vitamin E; ERD
      nephrectomized rats submitted to a regular diet containing vitamin E; SDD - sham
      rats submitted to a vitamin E-deficient diet; EDD nephrectomized rats submitted
      to a vitamin E-deficient diet. After 30 days the Experimental animals were
      submitted to 5/6 nephrectomy and the Controls were submitted to sham operation.
      The vitamin E levels of the SDD and EDD groups were significantly reduced (p <
      0.05) in plasma (4.92 +/- 1.22 and 8.37 +/- 2.09 mmol/L, respectively), liver
      (7.57 +/- 2.72 and 9.44 +/- 2.55mg/g tissue, respectively) and kidney (8.17 +/-
      2.38 and 9.40 +/- 3.10 mg/g tissue, respectively) when compared to the SRD and
      ERD groups. In contrast, in the EDD group the levels of thiobarbituric acid
      reactive substances, expressed as nmol/mg protein, were significantly increased
      (p < 0.05) in the liver (1.41 +/- 0.27) and kidney (1.67 +/- 0.47), and
      superoxide dismutase activity was significantly increased in the erythrocytes
      (4455.80 +/- 1322.63 Ug/Hb) compared to all other groups. The vitamin E-deficient
      diet associated with subtotal nephrectomy determined an increase in lipid
      peroxidation, suggesting an important role of free radicals in the development of
      chronic renal failure.

PMID- 12212822
TI  - Glutathione determination and a study of the activity of glutathione-peroxidase,
      glutathione-transferase, and glutathione-reductase in renal transplants.
AB  - The aim of this work is to study the temporary variation of oxidative stress in
      renal transplants, both in plasma and in erythrocytes (CR). In order to do so, we
      determined total glutathione (GST) levels, both oxidized (GSSG) and reduced
      (GSH), and the activity of enzymes, glutathione peroxidase (G-px), glutathione
      reductase (G-red) and glutathione transferase (GSt), in renal transplant
      patients. Determinations were made 48 h before the transplant 1 week and 2 weeks
      after the renal transplant. The results obtained confirm a high "oxidative
      stress" rate, resulting from the equilibrium between the production of free
      radicals and the activity of antioxidants, the former being higher
      proportionally. Immediately after the transplant there is an increase of
      oxidative stress, which results in an increase of G-red, a marked decrease of G
      px in plasma and in erythrocytes (CR) and an abrupt drop both in GST levels in
      plasma and in GSG (as well as in the [GSH]/[GSSG] relationship). As times goes
      on, after the transplant, there is a significant improvement in the activity of
      antioxidant enzymes, but there is no normalization, which is easily seen in the
      fact that total glutathione levels and the activity of the various enzymes
      approach the average values of the control group.

PMID- 12212823
TI  - Oxidative stress and hemodynamic maladjustment in chronic renal disease: a
      therapeutic implication.
AB  - Hemodynamic maladjustment with predominant constriction at the efferent arteriole
      has been encountered in a variety of clinical settings of glomerulonephropathy.
      In essence, it induces not only intraglomerular hypertension but also
      exaggeratedly reduces the peritubular capillary flow, which supplies the
      tubulointerstitial compartment. The hemodynamic maladjustment is believed to
      reflect a glomerular endothelial cell dysfunction. In this regard, oxidative
      stress and antioxidant defect are likely responsible for the glomerular
      endothelial dysfunction. Improvement in renal function was accomplished following
      the correction of oxidant and antioxidant imbalance with antioxidant therapy and
      vasodilators. Following such therapy, there was a correction in hemodynamic
      maladjustment with a decline in intraglomerular hydrostatic pressure and an
      increase in renal perfusion with a subsequent increase in renal functions namely
      creatinine clearance, glomerular filtration rate and a decline in FEMg.

PMID- 12212824
TI  - Urate homeostasis in polycystic kidney disease: comparison with chronic
      glomerulonephritic kidney.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) might affect urate
      homeostasis and clearance. Renal tubular urate transport was studied by means of
      probenecid (PB) and pyrazinamide (PZA) tests in individuals with ADPKD and normal
      renal function as well as various degrees of renal failure (49 patients).
      Comparisons were made between polycystic and chronic glomerulonephritic kidney
      (CGNK), as well as with controls (men with normal renal function). Patients with
      ADPKD and normal renal function showed plasma urate levels within normal range
      and normal renal urate handling. In contrast higher plasma urate levels comparing
      to controls were found in patients with CGNK and normal renal function. During
      the evolution of renal failure ADPKD patients showed lower urate plasma levels
      and higher renal clearance as well as, fractional urate excretion, comparing to
      CGNK patients with the same degree of renal failure. In conclusion patients with
      ADPKD and normal renal function have normal urate handling and plasma urate
      levels within normal range. With increasing severity of disease and during
      evolution of renal failure CGNK patients showed higher urate plasma levels and
      lower clearances comparing to ADPKD patients. When renal disease becomes more
      advanced there was no difference in renal urate handling between ADPKD and CGNK
      patients.

PMID- 12212825
TI  - Lack of effect of long-term use of angiotensin-converting enzyme inhibitors by
      hemodialysis patients on thirst and fluid weight gain.
AB  - Volume overload is a chronic, troublesome problem in many patients on
      hemodialysis. These patients suffer from hyperdipsia with inability to excrete
      water. Angiotensin-converting enzyme inhibitor (ACEI) has been shown to decrease
      thirst and interdialytic weight gain in 2-4 weeks of usage. We investigated the
      effect of long-term use of ACEI, as levels of angiotensin II tends to go back to
      normal level after 6 months of use. We compared hemodialysis patients on ACEI for
      more than 6 months to patients not on ACEI. Seven patients were taking ACEI
      compared to 51 controls in the other group. Almost one third of patients in each
      group had an interdialytic weight gain > 5% of dry weight. No significant
      difference was found between the two groups with regard to interdialytic weight
      gain, thirst and mouth dryness scores, and interdialytic mean blood pressure
      change. There was no demonstrable effect of angiotensin receptor blocking drugs
      on weight gain or thirst. We conclude that long-term ACEI may not continue to
      suppress inappropriate thirst and fluid intake after 6 months in hemodialysis
      patients.

PMID- 12212826
TI  - Influence of the endothelial nitric oxide synthase polymorphism on the
      progression of autosomal dominant polycystic kidney disease and IgA nephropathy.
AB  - BACKGROUND: The reason of variability of clinical course and progression to end
      stage renal failure (ESRF) of two widespread chronic nephropathies-autosomal
      dominant polycystic kidney disease (ADPKD) and IgA nephropathy (IGAN) is not
      clear. The endothelial dysfunction is considered in the number of factors
      possibly influencing the prognosis of these nephropathies. Our study tried to
      verify the hypothesis that endothelial nitric oxide synthase (ecNOS) gene
      polymorphisms in intron 4 could have some relevance to the progression of ADPKD
      and/or IgA nephropathy. METHODS: We examined 128 Czech patients with ADPKD (62
      males, 66 females) and 93 patients with IGAN (51 males, 42 females). As a control
      group we used 100 genetically unrelated healthy subjects (50 men, 50 women, mean
      age 51.2 +/- 8.2). The genomic DNA was amplified by polymerase chain reaction
      (PCR) and the products were separated on 1.5% agarose gel and visualized by
      ultraviolet transillumination. We compared homozygous subjects for ecNOSb allele
      with homozygous and heterozygous subjects for ecNOSa allele. RESULTS: The
      frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes were 19% (19/100) and 81%
      (81/100) in the control group. The frequencies of ecNOSa/b + a/a and ecNOSb/b
      genotypes in ADPKD patients were: 26.6% (8/30) and 73.4% (22/30) in ADPKD
      patients with normal renal function, 30% (9/30) and 70% (21/30) in ADPKD with
      ESRF, 35.2% (18/51) and 64.8% (33/51) in young ADPKD patients, 60% (12/20) and
      40% (8/20) in ADPKD patients with ESRF later than in 62 years. In IGAN the
      frequencies of ecNOSa/b + a/a and ecNOSb/b genotypes were 24% (12/50) and 76%
      (38/50) in IgA with normal renal function and 20.9 % (9/43) and 79.1% (38/43) in
      IgA with ESRF. CONCLUSION: Both in ADPKD and IGAN groups there was no significant
      difference in the frequencies of ecNOS genotypes between patients with normal
      renal function and age matched patients with ESRF and between patients with
      normal renal function and control group. The frequency of ecNOS a allele was
      significantly higher in a number limited group ADPKD patients with ESRF later
      than in 62 years (Chi-square test p < 0.05). This higher frequency of a allele
      among ADPKD patients with later onset of ESRF could suggest the trend of positive
      influence of a allele in ADPKD patients.

PMID- 12212827
TI  - Atypical initial manifestation of acute pyelonephritis in continuous image study:
      renal cystic feature.
AB  - Renal infection, including acute and chronic pyelonephritis, focal bacterial
      nephritis, renal and perinephric abscess, pyonephrosis and others, represents a
      spectrum of interrelated conditions. In recent years, computed tomography,
      ultrasound, nuclear scintigraphy, excretory urography (IVP) and magnetic
      resonance imaging have offered varying degrees of utility in evaluating renal
      infection. Although imaging in acute pyelonephritis has been extensively studied,
      this condition is a rare initial presentation as a renal cystic feature. This
      investigation presents a case of acute pyelonephritis, with an atypical initial
      imaging manifestation in renal cystic feature, which became a heterogeneous mass
      during follow up, and disappeared after treatment. Two conclusions can be drawn:
      first, a renal cystic lesion may be an initial presentation of acute
      pyelonephritis; secondly, the abnormalities of the ultrasonography imaging study
      of renal pyelonephritis persisted and progressed despite the improvement in
      clinical symptoms and laboratory findings, and displayed complete resolution of
      imaging abnormalities several months later.

PMID- 12212828
TI  - ApoA- and apoB-containing lipoproteins and Lp(a) concentration in non-dialyzed
      patients with chronic renal failure.
AB  - BACKGROUND: End-Stage renal disease is associated with accelerated
      atherosclerosis and a high incidence of cardiovascular disease. METHODS: The
      serum levels of lipids and apolipoproteins and Lp(a) were determined in 51
      patients with chronic renal failure (CRF) with various advancement, without
      interference of factors which might disturb Lp(a) metabolism and with proteinuria
      less than 0.5 g/24 h. The patients studied were divided into two groups: patients
      with moderate renal failure (CRF-M) and creatinine levels of 2-6mg/dL n = 27; and
      predialysis patients with end stage renal disease (ESRD) and creatinine levels
      higher than 8.5 mg/dL n=24. RESULTS: In both studied groups serum concentrations
      of triglycerides (TG), total apoCIII, apoCIIInonB, apoB:CIII were statistically
      increased, (except total cholestrol (TC) and LDL-cholestrol (LDL-C), apoB, total
      apoE, apoEnonB, apoB:E), while the levels of HDL-cholestrol (HDL-C) and apoAl
      significantly decreased. Lipid and lipoprotein ratios as risk factors of
      atherosclerosis were similar in both groups. The TC/HDL-C ratio increased, while
      that of HDL-C/ apoAI and apoAI/apoCIII decreased. Serum Lp(a) concentrations were
      significantly increased in both studied groups. The medians and ranges of Lp(a)
      concentration were similar in both groups. Serum Lp(a) levels correlated with
      total cholesterol (r=0.295; p < 0.05), LDL-C (r = 0.312; p < 0.05) and apoB (r =
      0.215; p < 0.05). In addition, no correlation was found between Lp(a) levels and
      albumin concentrations (r = 0.126; p = 0.421). CONCLUSION: Our results may
      indicate that the reduced levels of apoA-containing lipoproteins and increased TG
      rich apoB-containing lipoproteins and Lp(a) indicated a clear atherogenic pattern
      in early renal disease. Increased Lp(a) concentration may result in nonspecific
      synthesis or catabolism disturbances. Measurement and monitoring of lipoprotein
      family profiles offers a new means for selecting appropriate therapies targeted
      for normalizing dyslipidemia in non-dialyzed patients.

PMID- 12212829
TI  - Long-term monitoring of renal function in poly-traumatized intensive care
      patients.
AB  - INTRODUCTION: For the long-term monitoring of kidney function, polytraumatized
      patients were examined and routine as well as specialized parameters were
      compared. MATERIALS AND METHODS: 30 patients of the Surgical Intensive Care Unit
      (ICU) were examined daily over the entire period they stayed in the ICU. The
      patients were retrospectively classified as either survivors or deceased
      patients. Group 1 consisted of 20 patients who resided in the ICU for 11-15
      (Median 14) days before they could be transferred to a normal hospital unit.
      Group 2 consisted of 10 patients who had passed away after 13-18 (Median 16) days
      in the ICU. In addition to the routine parameters diuresis, serum creatinine and
      serum urea, specialized parameters for kidney function including the excretion
      rates of alpha1-microglobulin (alpha1-MG), N-Acetyl-beta-D-glucosaminidase (NAG),
      angiotensinase A (ATA) and immunoglobulin G (IgG) were determined. RESULTS:
      Similar biometric data were shown by all patients at admission into the ICU, but
      differences did exist regarding the Revised Trauma Score, Injury Severity Score
      and the APACHE-II-Score. In the period between the 5th and 8th day of intensive
      treatment almost all patients showed pathological excretion rates of tubular and
      glomerular parameters whereby no increased frequency of unusual events could be
      determined at these time-points. CONCLUSION: During treatment in the ICU, all
      examined patients showed at times pathological excretion rates of specialized
      kidney function parameters. Such transient damage was only apparent in a few of
      the patients when the standard parameters serum creatinine and serum urea were
      employed. In 90% of the surviving patients the kidney parameters had normalized
      until the time they were transferred, indicating that such parameters reflected
      the general state of health of these patients.

PMID- 12212830
TI  - The influence of l-carnitine supplementation on hematocrit and hemoglobin levels
      in patients with end stage renal failure on CAPD.
AB  - The influence of L-carnitine supplementation on hematocrit (Hct) and hemoglobin
      (Hb) levels, in patients suffering from end stage renal disease (ESRD) on
      maintenance hemodialysis, are well known from several studies. The data
      concerning the serum levels of carnitine, in patients with ESRD on continuous
      ambulatory peritoneal dialysis (CAPD) are contradictory, but most of them support
      that they are rather normal. In this study the effect of L-carnitine
      supplementation on Hct, and Hb levels were investigated in patients suffering
      from ESRD on CAPD. In the study 12 patients were included (5F, 7M), aged from 39
      to 92 years old (median 65.5 years), who were on CAPD for more than 6 months
      (from 6 to 15 months, mean +/- SD = 8.6 +/- 3.6), with normal serum ferrum and
      ferritin levels at the beginning of the study. Two grams of L-carnitine/ day per
      os (Superamin, Vianex Hellas), were administered in all the patients and the
      serum ferrum levels were tried to be kept stable, by exogenous ferrum
      administration, during the study period. If the Hct levels were more than 36% per
      month the erythropoietin (rHuEpo) dose of the patient was decreased monthly at
      the half dose/week. The changes of Hct, Hb, ferrum and ferritin levels, as well
      as the Indice de Rigidite (IR) of the erythrocytes were recorded, before and
      after the first, second and third month of the study period. Finally, the rHuEpo
      dose/ patient was registered monthly before and during the study. During the
      observations, Hct (35.4 +/- 3.3 vs. 38.1 +/- 3.4, ANOVA, p < 0.03) and Hb levels
      (11.0 +/- 1.1 vs. 11.9 +/- 1, ANOVA, p < 0.01), were significantly increased. On
      the other hand, rHuEpo dose necessity/patient/week was decreased significantly
      (3,833 +/- 3326 vs. 1,292 +/- 1,712, ANOVA, p < 0.01), in order to succeed the
      target Hct level. Furthermore, red blood cells IR also appeared to have a
      significant decrease (16.6 +/- 7.4 vs. 13.0 +/- 3.9, paired t-test, p < 0.03).
      Finally, the ferrum and ferritin levels were stable during the study period. It
      was concluded, that in patients on, CAPD the per os L-carnitine supplementation
      decreased, the red blood cells IR which contributes to the: (a) Increase of Hct
      and Hb levels and (b) decrease of the patients rHuEpo dose/week.

PMID- 12212831
TI  - Extra-renal abscess in chronic hemodialysis patients.
AB  - AIM: Infectious disease represents one of the major causes of morbidity and
      mortality in hemodialysis patients. Extra-renal abscess constitutes a specific
      form of infection. The aim of this study was to evaluate and analyze the clinical
      characteristics of extra-renal abscess in chronic hemodialysis patients. METHODS:
      We retrospectively studied the extra-renal abscess among chronic hemodialysis
      patients in Chang Gung Memorial Hospital at Kaohsiung, Taiwan. The records of
      2,168 chronic hemodialysis patients from October 1986 to January 2000, were
      studied. The clinical features were reviewed and analyzed. RESULTS: Sixteen
      patients who were enrolled during the study period developed extra-renal abscess.
      Ten of them were male. The mean age was 59.2 +/- 11.8 years old. More than half
      of the patients had diabetes (53.6%, 9/16). The locations of extra-renal abscess
      in these patients were liver (8/16), lung (5/16), spleen (1/16), perianal region
      (1/16), psoas muscle (1/16), and prostate (1/16). One patient had concurrent
      liver and spleen abscesses. All patients presented with fever and chills.
      Laboratory studies revealed leukocytosis and thrombocytopenia in 2/3 of the
      patients. The patients were associated with malnutrition status with lower serum
      albumin level (2.94 +/- 0.55 gm/dL) and lower nPCR (normalized protein catabolism
      rate; 0.84 +/- 0.11 gm/Kg/day) comparing to the other hemodialysis patients
      (albumin: 4.05 +/- 0.47 gm/dL; nPCR: 1.14 +/- 0.31gm/kg/day). There was no
      significant difference in kt/V between the patients with (1.28 +/- 0.34) or
      without abscess formation (1.47 +/- 0.36). The major causative pathogen was
      Klebsiella pnewnoniae. Parenteral antibiotic treatment is sufficient to treat
      most of the diseases, except 2 patients who needed surgical intervention. Twelve
      patients recovered after 2-3 weeks of treatment. CONCLUSIONS: The study indicated
      that extra-renal abscess is rare in chronic hemodialysis patients. The abscesses
      occurred mostly in liver. Diabetes mellitus and poor nutrition status were the
      important predisposing factors. Gram-negative bacilli, K. pneumoniae, were the
      major pathogen. Most of the patients responded to parenteral antibiotics and
      surgical draining.

PMID- 12212832
TI  - Successful treatment of idiopathic membranous glomerulonephritis complicated with
      renal vein thrombosis with FK506.

PMID- 12212833
TI  - N-acetylcysteine as salvage therapy in cisplatin nephrotoxicity.
AB  - N-acetylcysteine (NAC) repletes intracellular stores of reduced glutathione and
      may be a scavenger of oxygen free radicals. We report a 52-year-old female who
      developed acute renal insufficiency after administration of one dose of 150 mg of
      cisplatin for treatment of squamous cell cancer of the esophagus. Her blood urea
      nitrogen and creatinine rose from 12 and 0.7 mg/dL, respectively, to 24 and 1.8
      mg/dL on day 5 after cisplatin. On that day the patient was begun on NAC,
      starting with a loading dose of 140-mg/kg-body weight followed by 70mg/kg every
      4h for 4 days. Two days after starting NAC her renal function began to improve,
      and although she failed to complete a full course of the drug, by day 10 her
      serum creatinine had fallen to 0.8 mg/dL. A previous report showed that N
      acetylcysteine might reverse cisplatin-induced renal toxicity. Our case supports
      this hypothesis.

PMID- 12212834
TI  - Diarrhea associated acute renal failure in a patient with Salmonella enteritidis
      sepsis.
AB  - Salmonella enteritidis infection occurs primarily in animals and often results in
      self-limited gastroenteritis in accidental cross contamination in human. However,
      the acute renal failure could be a rare but serious complication of the S.
      enteritidis infection. We report one case of acute renal failure from severe
      dehydration caused by S. enteritidis food poisoning. The acute renal failure
      completely recovered after hydration and antibiotic treatment.

PMID- 12212835
TI  - Acute renal failure in neuroleptic malignant syndrome.
AB  - We report a patient with neuroleptic malignant syndrome (NMS) who developed acute
      renal failure and was successfully treated by hemodialysis. A 60-year-old man
      with a 26-year history of schizophrenia had been treated with thioridazine and
      sulpiride. He was admitted to our hospital for muscular rigidity and oliguria.
      After the diagnosis of NMS with acute renal failure was established, thioridazine
      and sulpiride were discontinued and hemodialysis was instituted. Renal function
      gradually improved and hemodialysis was discontinued after 17th treatment. We
      also reviewed 57 cases of NMS with acute renal failure reported in the
      literature. To our knowledge, 26 years is the longest latency between initiation
      of neuroleptic drug treatment and onset of NMS. Our review of reported NMS cases
      with acute renal failure identified those risks for poor prognosis as high level
      of BUN, age and female gender.

PMID- 12212836
TI  - The involvement of mammalian and plant FK506-binding proteins (FKBPs) in
      development.
AB  - The FK506-binding proteins (FKBPs) are peptidyl prolyl cis/trans isomerases and
      the information gathered in the last 10 years reveals their involvement in
      diverse biological systems affecting the function and structure of target
      proteins. Members of the FKBP family were shown to be growth-regulated and
      participate in signal transduction. In this review we have chosen to focus on a
      few examples of the mammalian and plant systems in which members of the FKBP
      family have been demonstrated to affect the function of proteins or development.
      The technologies that enable production of knockout mice, Arabidopsis mutants and
      overexpression in transgenic organisms have revealed the contribution of FKBP to
      development in higher eukaryotes. It appears that members of the FKBP family have
      conserved some of their basic functions in the animal and plant kingdom, whereas
      other functions became unique. Studies that will take advantage of the full
      genome sequence available for Arabidopsis and the human genome, DNA chip
      technologies and the use of transgenic complementation system will contribute to
      the elucidation of the molecular mechanism and biological function of FKBPs.

PMID- 12212838
TI  - Cotton alpha-globulin promoter: isolation and functional characterization in
      transgenic cotton, Arabidopsis, and tobacco.
AB  - Globulins are the most abundant seed storage proteins in cotton and, therefore,
      their regulatory sequences could potentially provide a good source of seed
      specific promoters. We isolated the putative promoter region of cotton alpha
      globulin B gene by gene walking using the primers designed from a cotton staged
      embryo cDNA clone. PCR amplified fragment of 1108 bp upstream sequences was fused
      to gusA gene in the binary vector pBI101.3 to create the test construct. This was
      used to study the expression pattern of the putative promoter region in
      transgenic cotton, Arabidopsis, and tobacco. Histochemical GUS analysis revealed
      that the promoter began to express during the torpedo stage of seed development
      in tobacco and Arabidopsis, and during cotyledon expansion stage in cotton. The
      activity quickly increased until embryo maturation in all three species.
      Fluorometric GUS analysis showed that the promoter expression started at 12 and
      15 dpa in tobacco and cotton, respectively, and increased through seed
      maturation. The strength of the promoter expression, as reflected by average GUS
      activity in the seeds from primary transgenic plants, was vastly different
      amongst the three species tested. In Arabidopsis, the activity was 16.7% and in
      tobacco it was less than 1% of the levels detected in cotton seeds. In
      germinating seedlings of tobacco and Arabidopsis, GUS activity diminished until
      it was completely absent 10 days post imbibition. In addition, absence of
      detectable level of GUS expression in stem, leaf, root, pollen, and floral bud of
      transgenic cotton confirmed that the promoter is highly seed-specific. Analysis
      of GUS activity at individual seed level in cotton showed a gene dose effect
      reflecting their homozygous or hemizygous status. Our results show that this
      promoter is highly tissue-specific and it can be used to control transgene
      expression in dicot seeds.

PMID- 12212837
TI  - Targeted expression of human serum albumin to potato tubers.
AB  - Complementary DNA expression of mature human serum albumin was engineered into
      potato plants under the transcriptional control of patatin B33 promoter and
      potato proteinase inhibitor II terminator. Protein secretion was achieved by
      using the signal sequence from potato proteinase inhibitor II. Recombinant
      albumin accumulated up to 0.2% of total soluble tuber protein in single
      transformant lines, regardless of the potato cultivar used. Electrophoretic
      mobility and N-terminal amino acid sequence analysis of partially purified
      recombinant albumin confirmed proper processing of an immune responsive
      recombinant albumin, and revealed that the proteinase inhibitor II signal
      sequence was correctly removed. No further optimisation of these yields was
      obtained by HSA expression in patatin antisense plants (line Pas58). Subcellular
      localisation showed that recombinant protein was successfully targeted to the
      apoplast. Potato tubers may be used, by applying this technology, to produce
      other heterologous proteins of interest in the biopharmaceutical industry.

PMID- 12212839
TI  - Conditional over-expression of estrogen receptor alpha in a transgenic mouse
      model.
AB  - Attempts to delineate the mechanisms of estrogen action have promoted the
      creation of several estrogen receptor alpha (ERalpha) mouse models in the past
      decade. These traditional models are limited by the fact that the receptors are
      either absent or present throughout all stages of development. The purpose of
      this work was to develop a conditional transgenic model that would provide an in
      vivo method of controlling the spatial and temporal regulation of ERalpha
      expression. The tetracycline responsive system was utilized. Three lines of
      transgenic mice carrying a transgene composed of the coding sequence for murine
      ERalpha placed under the regulatory control of a tet operator promoter (tet-op)
      were generated. These three lines of tet-op-mERa mice were each mated to an
      established line of transgenic mice expressing a tetracycline-dependent
      transactivator protein (tTA) from the mouse mammary tumor virus-long terminal
      repeat (MMTV-LTR). Double transgenic MMTV-tTA/tet-op-mERalpha mice were produced.
      All three lines demonstrated dominant gain of ERalpha shown by RT-PCR,
      immunoprecipitation, and immunohistochemistry. Transgene-specific ERalpha was
      expressed in numerous tissues including the mammary gland, salivary gland,
      testis, seminal vesicle, and epididymis. Expression was silenced by
      administration of doxycycline in the drinking water. This model can be utilized
      to evaluate the consequences of ERalpha dominant gain in targeted tissues at
      specific times during development. In this study dominant gain of ERalpha was
      associated with a reduction in epididymal/vas deferens and seminal vesicle
      weights consistent with the proposed action of ERalpha on fluid transport in the
      male reproductive tract. Combining this model with other dominant gain and gene
      knockout mouse models will be useful for testing effects of ERalpha action in
      combination with specific gene products and to evaluate if developmental and
      stage-specific expression of ERalpha can rescue identified phenotypes in gene
      knockout mice.

PMID- 12212840
TI  - Overexpression of the wheat FK506-binding protein 73 (FKBP73) and the heat
      induced wheat FKBP77 in transgenic wheat reveals different functions of the two
      isoforms.
AB  - The FK506-binding proteins (FKBPs) belong to the peptidyl prolyl cis-trans
      isomerase (PPIase) family, and catalyse the rotation of the peptide bond
      preceding a proline. They are conserved in organisms from bacteria to man. In
      order to understand the function of plant FKBP isoforms, we have produced
      transgenic wheat plants overexpressing each of the two wheat FKBPs: wFKBP73
      (which is expressed in young vegetative and reproductive tissues under normal
      growth conditions) and wFKBP77 (which is induced by heat stress). Transgenic
      lines overexpressing wFKBP77 at 25 degrees C showed major morphological
      abnormalities, specifically relating to height, leaf shape, spike morphology and
      sterility. In these plants, the levels of hsp90 mRNA were over two fold higher
      than in controls, indicating a common regulatory pathway shared between wFKBP77
      and Hsp90. Transgenic lines overexpressing wFKBP73 showed normal vegetative
      morphology, but the grain weight and composition was altered, corresponding to
      changes in amylase activity during seed development.

PMID- 12212841
TI  - High efficiency transgene segregation in co-transformed maize plants using an
      Agrobacterium tumefaciens 2 T-DNA binary system.
AB  - For regulatory issues and research purposes it would be desirable to have the
      ability to segregate transgenes in co-transformed maize. We have developed a
      highly efficient system to segregate transgenes in maize that was co-transformed
      using an Agrobacterium tumefaciens 2 T-DNA binary system. Three vector treatments
      were compared in this study; (1) a 2 T-DNA vector, where the selectable marker
      gene bar (confers resistance to bialaphos) and the beta-glucuronidase (GUS)
      reporter gene are on two separate T-DNA's contained on a single binary vector;
      (2) a mixed strain treatment, where bar and GUS are contained on single T-DNA
      vectors in two separate Agrobacterium strains; (3) and a single T-DNA binary
      vector containing both bar and GUS as control treatment. Bialaphos resistant
      calli were generated from 52 to 59% of inoculated immature embryos depending on
      treatment. A total of 93.4% of the bialaphos selected calli from the 2 T-DNA
      vector treatment exhibited GUS activity compared to 11.7% for the mixed strain
      treatment and 98.2% for the cis control vector treatment. For the 2 T-DNA vector
      treatment, 86.7% of the bialaphos resistant/GUS active calli produced R0 plants
      exhibiting both transgenic phenotypes compared to 10% for the mixed strain
      treatment and 99% for the single T-DNA control vector treatment. A total of 87
      Liberty herbicide (contains bialaphos as the active ingredient) resistant/GUS
      active R0 events from the 2 T-DNA binary vector treatment were evaluated for
      phenotypic segregation of these traits in the R1 generation. Of these R0 events,
      71.4% exhibited segregation of Liberty resistance and GUS activity in the R1
      generation. A total of 64.4% of the R0 2 T-DNA vector events produced Liberty
      sensitive/GUS active (indicating selectable-marker-free) R1 progeny. A high
      frequency of phenotypic segregation was also observed using the mixed strain
      approach, but a low frequency of calli producing R0 plants displaying both
      transgenic phenotypes makes this method less efficient. Molecular analyses were
      then used to confirm that the observed segregation of R1 phenotypes were highly
      correlated to genetic segregation of the bar and GUS genes. A high efficiency
      system to segregate transgenes in co-transformed maize plants has now been
      demonstrated.

PMID- 12212843
TI  - Elite Indica transgenic rice plants expressing modified Cry1Ac endotoxin of
      Bacillus thuringiensis show enhanced resistance to yellow stem borer (Scirpophaga
      incertulas).
AB  - Bt-transgenics of elite indica rice breeding lines (IR-64, Pusa Basmati-1 and
      Karnal Local) were generated through biolistic or Agrobacterium-mediated
      approaches. A synthetic cry1Ac gene, codon optimised for rice and driven by the
      maize ubiquitin-1 promoter, was used. Over 200 putative transformants of IR-64
      and Pusa Basmati-1 and 26 of the Karnal Local were regenerated following use of
      the hpt (hygromycin phosphotransferase) selection system. Initial transformation
      frequency was in the range of 1 to 2% for particle bombardment while it was
      comparatively higher (approximately 9%) for Agrobacterium. An improved selection
      procedure, involving longer selection on the antibiotic-supplemented medium,
      enhanced the frequency of Bt-transformants and reduced the number of escapes.
      Molecular evaluation revealed multiple transgene insertions in transformants,
      whether generated through biolistic or Agrobacterium. In the latter case, it was
      also observed that all genes on the T-DNA do not necessarily get transferred as
      an intact insert. Selected Bt-lines of IR-64 and Pusa Basmati-1, having Bt-titers
      of 0.1% (of total soluble protein) and above were evaluated for resistance
      against manual infestation of freshly hatched neonate larvae of yellow stem
      borers collected from a hot spot stem borer infested area in northern India.
      Several Bt-lines were identified showing 100% mortality of larvae, within 4-days
      of infestation, in cut-stem as well as vegetative stage whole plant assays.
      However, there was an occasional white head even among such plants when assayed
      at the reproductive stage. Results are discussed in the light of resistance
      management strategies for deployment of Bt-rice.

PMID- 12212842
TI  - General utility of the chicken betaB1-crystallin promoter to drive protein
      expression in lens fiber cells of transgenic mice.
AB  - Transgenic mouse technology has been very valuable for the study of lens fiber
      cells since they can not be propagated in cell culture. The targeting of
      transgenes to the lens has traditionally been done with the alphaA-crystallin
      promoter. However, while lens-specific, transgenic lines made with the alphaA
      crystallin promoter express the transgene at levels 100-300-fold lower than
      endogenous alphaA-crystallin. Here we propose an alternative, the chicken betaB1
      crystallin promoter (-432/+30). Transgenic mice made with this promoter have
      successfully expressed CAT, d/n m-calpain, Weel, and betaB2-crystallin mRNA at
      levels comparable to the endogenous betaB1-crystallin gene and no eye
      abnormalities such as cataracts, have resulted. All of the transgenic lines made
      with the chicken betaB1-crystallin promoter have expressed the transgene in the
      lens fiber cells, and the best lines express at levels close to endogenous betaB1
      crystallin. While RNA expression is very high, only moderate protein expression
      has been achieved, implying that the high protein expression of the crystallins
      is partially controlled at the level of translation. Thus, the chicken betaB1
      crystallin promoter directs high level RNA expression to lens fiber cells, which
      may be especially useful for the expression of ribozyme and anti-sense RNAs in
      addition to ectopic proteins.

PMID- 12212844
TI  - The use of the uromodulin promoter to target production of recombinant proteins
      into urine of transgenic animals.
AB  - A uromodulin promoter has been isolated, sequenced, and used to generate two sets
      of transgenic mice for expression of the lacZ marker gene and for production of
      the human recombinant erythropoietin (rhEPO) in urine. We demonstrated that the
      5.6-kb fragment of the uromodulin gene containing the 3.7-kb promoter area and,
      both the first exon and part of the second exon, were sufficient to provide
      kidney-specific expression of the lacZ gene. Histological analysis of the lacZ
      expression pattern revealed beta-galactosidase activity specifically in the thick
      limb of Henle's loop. However, due to random integration of the transgene,
      ectopic expression was detected in some transgenic lines. Analysis of the EPO
      transgenic mice showed that rhEPO was secreted into the urine of founder mice (up
      to 6 ng/ml). We were able to breed and analyze only two sublines with a very low
      expression level of rhEPO (up to 260 pg/ml). All of our transgenic mice
      expressing rhEPO in urine developed disease symptoms similar to polycythemia in
      humans. These included a considerable increase in red blood cell counts,
      hemoglobin concentration, and hematocrit concomitant with severe
      thrombocytopenia, all of which were detected in the rhEPO-expressing mice.
      Although our model did not prove to be beneficial for commercial production of
      rhEPO, we concluded that the uromodulin promoter could be useful for expression
      of other important therapeutic proteins into the urine of transgenic animals.

PMID- 12212845
TI  - Cloning of the chrysanthemum UEP1 promoter and comparative expression in florets
      and leaves of Dendranthema grandiflora.
AB  - To attain high transgene expression in petal tissue of ray florets of
      chrysanthemum an endogenous ubiquitin extension protein (UEP1) promoter was
      cloned and tested with the beta-glucuronidase (GUS) reporter gene. Expression
      levels were compared with four heterologous promoters: chalcone synthase (chs-A)
      and zinc finger transcription factor (EPF2-5) from petunia, eceriferum (CER6)
      from Arabidopsis and multicystatin (PMC) from potato. The comparison of the
      expression levels of the different constructs in ray florets, disc florets, and
      leaves is presented. The highest mean expression in petal tissue of ray and disc
      florets was conferred by the UEP1 promoter, followed by CER6 and EPF2-5. The UEP1
      promoter in ray florets confers over 50-fold enhancement in expression as
      compared to CaMV 35S-based promoters.

PMID- 12212846
TI  - The 5' and 3' domains of yeast U6 snRNA: Lsm proteins facilitate binding of Prp24
      protein to the U6 telestem region.
AB  - The 5' and 3' domains of yeast U6 snRNA contain sequences that are thought to be
      important for binding to Prp24 and Lsm proteins. By extensive mutational analysis
      of yeast U6 snRNA, we confirmed that the 3' terminal uridine tract of U6 snRNA is
      important for U6 binding to Lsm proteins in yeast. Binding of Prp24 protein to U6
      RNA is dependent on or is strongly enhanced by U6 binding of Lsm proteins. This
      supports a model for U6 snRNP assembly in which U6 RNA binds to the Lsm2-8 core
      prior to binding Prp24 protein. Using compensatory base-pairing analysis, we show
      that at least half of the recently identified U6 telestem as well as a nucleotide
      sequence in the other half of the telestem are important for binding of U6 RNA to
      Prp24 protein. Surprisingly, disruption of base pairing in the unconfirmed half
      of the telestem enhanced U6-Prp24 binding. Truncation of the entire 3' terminal
      domain or nearly the entire 5' terminal domain of yeast U6 allowed for detectable
      levels of splicing to proceed in vitro. In addition to gaining knowledge of the
      function of the 5' and 3' domains of yeast U6, our results help define the
      minimal set of requirements for yeast U6 RNA function in splicing. We present a
      revised secondary structural model of yeast U6 snRNA in free U6 snRNPs.

PMID- 12212848
TI  - Domains on the hepatitis C virus internal ribosome entry site for 40s subunit
      binding.
AB  - The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) RNA is
      known to interact with the 40S ribosomal subunit alone, in the absence of any
      additional initiation factors or Met-tRNAi. Previous work from this laboratory on
      the 80S and 48S ribosomal initiation complexes involving the HCV IRES showed that
      stem-loop III, the pseudoknot domain, and some coding sequence were protected
      from pancreatic RNase digestion. Stem-loop II is never protected by these
      complexes. Furthermore, there is no prior evidence reported showing extensive
      direct binding of stem-loop II to ribosomes or subunits. Using direct analysis of
      RNase-protected HCV IRES domains bound to 40S ribosomal subunits, we have
      determined that stem-loops II and III and the pseudoknot of the HCV IRES are
      involved in this initial binding step. The start AUG codon is only minimally
      protected. The HCV-40S subunit binary complex thus involves recognition and
      binding of stem-loop II, revealing its role in the first step of a multistep
      initiation process that may also involve rearrangement of the bound IRES RNA as
      it progresses.

PMID- 12212847
TI  - Specific degradation of 3' regions of GUS mRNA in posttranscriptionally silenced
      tobacco lines may be related to 5'-3' spreading of silencing.
AB  - Target regions for posttranscriptional silencing of transgenes often reside in
      the 3' region of the coding sequence, although there are exceptions. To resolve
      if the target region is determined by the gene undergoing silencing rather than
      by the structure of the transgene loci or the plant genetic background, we have
      performed detailed analyses of target regions in three spontaneously beta
      glucuronidase (GUS) silencing tobacco lines of different origin. From
      quantitative cosuppression experiments, we show that the main target region in
      all three tobacco lines is found within the 3' half of the GUS coding region but
      upstream of the last 200 nt. The quantities of small (21-25 nt) RNAs homologous
      to 5' or 3' regions of the GUS coding sequence were found to correlate
      approximately with the target strength of the corresponding regions. These
      results suggest that transgene locus structure and plant genetic background are
      not major determinants of silencing target regions. We also show that virus
      induced gene silencing (VIGS) of GUS in Nicotiana benthamiana is induced equally
      effectively with Potato virus X carrying either the 5' or 3' third of the GUS
      coding region. This indicates that both regions can act as efficient inducers as
      well as targets of posttranscriptional silencing, although the 3' region is the
      predominant target region in the spontaneously silencing transgenic plant lines
      examined. Finally, we investigated spreading of the target region in the N.
      benthamiana plants undergoing VIGS. Surprisingly, only evidence for spreading of
      the target region in the 5'-3' direction was obtained. This finding may help
      explain why the majority of target regions examined to date lie within the 3'
      region of transgenes.

PMID- 12212849
TI  - Chemical modification of nucleotide bases and mRNA editing depend on hexamer or
      nucleoprotein phase in Sendai virus nucleocapsids.
AB  - The minus-strand genome of Sendai virus is an assembly of the nucleocapsid
      protein (N) and RNA, in which each N subunit is associated with precisely 6 nt.
      Only genomes that are a multiple of 6 nt long replicate efficiently or are found
      naturally, and their replication promoters contain sequence elements with hexamer
      repeats. Paramyxoviruses that are governed by this hexamer rule also edit their P
      gene mRNA during its synthesis, by G insertions, via a controlled form of viral
      RNA polymerase "stuttering" (pseudo-templated transcription). This stuttering is
      directed by a cis-acting sequence (3' UNN UUUUUU CCC), whose hexamer phase is
      conserved within each virus group. To determine whether the hexamer phase of a
      given nucleotide sequence within nucleocapsids affected its sensitivity to
      chemical modification, and whether hexamer phase of the mRNA editing site was
      important for the editing process, we prepared a matched set of viruses in which
      a model editing site was displaced 1 nt at a time relative to the genome ends.
      The relative abilities of these Sendai viruses to edit their mRNAs in cell
      culture infections were examined, and the ability of DMS to chemically modify the
      nucleotides of this cis-acting signal within resting viral nucleocapsids was also
      studied. Cytidines at hexamer phases 1 and 6 were the most accessible to chemical
      modification, whereas mRNA editing was most extensive when the stutter-site C was
      in positions 2 to 5. Apparently, the N subunit imprints the nucleotide sequence
      it is associated with, and affects both the initiation of viral RNA synthesis and
      mRNA editing. The N-subunit assembly thus appears to superimpose another code
      upon the genetic code.

PMID- 12212850
TI  - How Slu7 and Prp18 cooperate in the second step of yeast pre-mRNA splicing.
AB  - Slu7 and Prp18 act in concert during the second step of yeast pre-mRNA splicing.
      Here we show that the 382-amino-acid Slu7 protein contains two functionally
      important domains: a zinc knuckle (122CRNCGEAGHKEKDC135) and a Prp18-interaction
      domain (215EIELMKLELY224). Alanine cluster mutations of 215EIE217 and 221LELY224
      abrogated Slu7 binding to Prp18 in a two-hybrid assay and in vitro, and elicited
      temperature-sensitive growth phenotypes in vivo. Yet, the mutations had no impact
      on Slu7 function in pre-mRNA splicing in vitro. Single alanine mutations of zinc
      knuckle residues Cys122, His130, and Cys135 had no effect on cell growth, but
      caused Slu7 function during pre-mRNA splicing in vitro to become dependent on
      Prp18. Specifically, zinc knuckle mutants required Prp18 in order to bind to the
      spliceosome. Compound mutations in both Slu7 domains (e.g., C122A-EIE, H130A-EIE,
      and C135A-EIE) were lethal in vivo and abolished splicing in vitro, suggesting
      that the physical interaction between Slu7 and Prp18 is important for cooperation
      in splicing. Depletion/reconstitution studies coupled with immunoprecipitations
      suggest that second step factors are recruited to the spliceosome in the
      following order: Slu7 --> Prp18 --> Prp22. All three proteins are released from
      the spliceosome after step 2 concomitant with release of mature mRNA.

PMID- 12212851
TI  - High-affinity hnRNP A1 binding sites and duplex-forming inverted repeats have
      similar effects on 5' splice site selection in support of a common looping out
      and repression mechanism.
AB  - High-affinity binding sites for the hnRNP A1 protein stimulate the use of a
      distal 5' splice site in mammalian pre-mRNAs. Notably, strong A1-mediated shifts
      in splice site selection are not accompanied by equivalent changes in the
      assembly of U1 snRNP-containing complexes on competing 5' splice sites. To
      explain the above results, we have proposed that an interaction between hnRNP A1
      molecules bound to high-affinity sites loops out the internal 5' splice site.
      Here, we present additional evidence in support of the looping out model. First,
      replacing A1 binding sites with sequences that can generate a loop through RNA
      duplex formation activates distal 5' splice site usage in an equivalent manner.
      Second, increasing the distance between the internal 5' splice site and flanking
      A1 binding sites does not compromise activation of the distal 5' splice site.
      Similar results were obtained with pre-mRNAs carrying inverted repeats. Using a
      pre-mRNA containing only one 5' splice site, we show that splicing is repressed
      when flanked by two high-affinity A1 binding sites or by inverted repeats, and
      that inactivation of the internal 5' splice site is sufficient to elicit a strong
      increase in the use of the distal donor site. Our results are consistent with the
      view that the binding of A1 to high-affinity sites promotes loop formation, an
      event that would repress the internal 5' splice site and lead to distal 5' splice
      site activation.

PMID- 12212852
TI  - Expression of the essential mRNA export factor Yra1p is autoregulated by a
      splicing-dependent mechanism.
AB  - Recent evidence supports the idea that pre-mRNA splicing and mRNA export are
      mechanistically coupled. In metazoans, this process appears to be mediated by a
      multicomponent complex, which associates with the spliced RNA upstream of the
      exon-exon junction. One of these components (Aly/REF) has a homolog in the
      budding yeast Saccharomyces cerevisiae known as Yra1p. The YRA1 gene is essential
      for growth and required for mRNA export. Notably, YRA1 is one of the only
      approximately 5% intron-containing genes in yeast. Moreover, the YRA1 intron has
      several unusual features and is conserved in other budding yeast species.
      Previously, overexpression of intronless YRA1 was shown to be toxic. We show here
      that overexpression of the intron-containing gene results in increased levels of
      unspliced pre-mRNA but normal levels of Yra1 protein; conversely, expression of
      the cDNA results in increased levels of protein and accumulation of nuclear
      poly(A)+ RNA. Two additional lines of evidence suggest that expression of Yra1p
      is autoregulated: First, expression of excess Yra1p from a plasmid reduces the
      level of tagged, chromosomal Yra1p, and, second, this effect requires wild-type
      protein. Replacement of the YRA1 intron with that of other S. cerevisiae genes
      cannot rescue the dominant-negative growth defect of intronless YRA1. We conclude
      that the level of Yra1p is negatively autoregulated by a mechanism that involves
      splicing of its unusual intron. Tight control of the levels of Yra1p might be
      necessary to couple the rates of pre-mRNA splicing and mRNA export.

PMID- 12212855
TI  - Evaluation of an adaptive, directional-microphone hearing aid.
AB  - The effectiveness of adaptive directional processing for improvement of speech
      recognition in comparison to non-adaptive directional and omni-directional
      processing was examined across four listening environments intended to simulate
      those found in the real world. The test environment was a single, moderately
      reverberant room with four loudspeaker configurations: three with fixed discrete
      noise source positions and one with a single panning noise source. Sentence
      materials from the Hearing in Noise Test (HINT) and Connected Speech Test (CST)
      were selected as test materials. Speech recognition across all listening
      conditions was evaluated for 20 listeners fitted binaurally with Phonak Claro
      behind-the-ear (BTE) style hearing aids. Results indicated improved speech
      recognition performance with adaptive and non-adaptive directional processing
      over that measured with the omnidirectional processing across all four listening
      conditions. While the magnitudes of directional benefit provided to subjects
      listening in adaptive and fixed directional modes were similar in some listening
      environments, a significant speech recognition advantage was measured for the
      adaptive mode in specific conditions. The advantage for adaptive over fixed
      directional processing was most prominent when a competing noise was presented
      from the listener's sides (both fixed and panning noise conditions), and was
      partially predictable from electroacoustically measured directional pattern data.

PMID- 12212853
TI  - Comparative studies of frameshifting and nonframeshifting RNA pseudoknots: a
      mutational and NMR investigation of pseudoknots derived from the bacteriophage T2
      gene 32 mRNA and the retroviral gag-pro frameshift site.
AB  - Mutational and NMR methods were used to investigate features of sequence,
      structure, and dynamics that are associated with the ability of a pseudoknot to
      stimulate a -1 frameshift. In vitro frameshift assays were performed on
      retroviral gag-pro frameshift-stimulating pseudoknots and their derivatives, a
      pseudoknot from the gene 32 mRNA of bacteriophage T2 that is not naturally
      associated with frameshifting, and hybrids of these pseudoknots. Results show
      that the gag-pro pseudoknot from human endogenous retrovirus-K10 (HERV)
      stimulates a -1 frameshift with an efficiency similar to that of the closely
      related retrovirus MMTV. The bacteriophage T2 mRNA pseudoknot was found to be a
      poor stimulator of frameshifting, supporting a hypothesis that the retroviral
      pseudoknots have distinctive properties that make them efficient frameshift
      stimulators. A hybrid, designed by combining features of the bacteriophage and
      retroviral pseudoknots, was found to stimulate frameshifting while retaining
      significant structural similarity to the nonframeshifting bacteriophage
      pseudoknot. Mutational analyses of the retroviral and hybrid pseudoknots were
      used to evaluate the effects of an unpaired (wedged) adenosine at the junction of
      the pseudoknot stems, changing the base pairs near the junction of the two stems,
      and changing the identity of the loop 2 nucleotide nearest the junction of the
      stems. Pseudoknots both with and without the wedged adenosine can stimulate
      frameshifting, though the identities of the nucleotides near the stem1/stem2
      junction do influence efficiency. NMR data showed that the bacteriophage and
      hybrid pseudoknots are similar in their local structure at the junction of the
      stems, indicating that pseudoknots that are similar in this structural feature
      can differ radically in their ability to stimulate frameshifting. NMR methods
      were used to compare the internal motions of the bacteriophage T2 pseudoknot and
      representative frameshifting pseudoknots. The stems of the investigated
      pseudoknots are similarly well ordered on the time scales to which nitrogen-15
      relaxation data are sensitive; however, solvent exchange rates for protons at the
      junction of the two stems of the nonframeshifting bacteriophage pseudoknot are
      significantly slower than the analogous protons in the representative
      frameshifting pseudoknots.

PMID- 12212856
TI  - Occupational exposure to noise decreases otoacoustic emission efferent
      suppression.
AB  - With the discovery of otoacoustic emissions (OAEs), the efferent cochlear system
      has become accessible for investigation in humans. Recently, it has been
      suggested that contralateral sound activated OAE efferent suppression may provide
      an early indication of auditory damage due to exposure to noise. In this study,
      OAE efferent suppression in normally hearing subjects, occupationally exposed to
      noise, was compared with respective effects in healthy, non-exposed subjects. The
      noise-exposed group exhibited higher mean hearing thresholds at frequencies 4, 6
      and 10 kHz (p < 0.01) and lower-level transient-evoked otoacoustic emission
      (TEOAE) and distortion-product otoacoustic emission (DPOAE) at a frequency of 4
      kHz (not significant). TEOAE efferent suppression was moderately decreased,
      whereas DPOAE efferent suppression was negligible, in the exposed group compared
      to non-exposed subjects. The results of the study suggest that OAEs, particularly
      DPOAE contralateral suppression, are likely to become a valuable method for
      assessing early hearing damage caused by exposure to noise.

PMID- 12212854
TI  - The conserved central domain of yeast U6 snRNA: importance of U2-U6 helix Ia in
      spliceosome assembly.
AB  - In the pre-mRNA processing machinery of eukaryotic cells, U6 snRNA is located at
      or near the active site for pre-mRNA splicing catalysis, and U6 is involved in
      catalyzing the first chemical step of splicing. We have further defined the roles
      of key features of yeast U6 snRNA in the splicing process. By assaying
      spliceosome assembly and splicing in yeast extracts, we found that mutations of
      yeast U6 nt 56 and 57 are similar to previously reported deletions of U2 nt 27 or
      28, all within yeast U2-U6 helix Ia. These mutations lead to the accumulation of
      yeast A1 spliceosomes, which form just prior to the Prp2 ATPase step and the
      first chemical step of splicing. These results strongly suggest that, at a late
      stage of spliceosome assembly, the presence of U2-U6 helix Ia is important for
      promoting the first chemical step of splicing, presumably by bringing together
      the 5' splice site region of pre-mRNA, which is base paired to U6 snRNA, and the
      branchsite region of the intron, which is base paired to U2 snRNA, for activation
      of the first chemical step of splicing, as previously proposed by Madhani and
      Guthrie [Cell, 1992, 71: 803-817]. In the 3' intramolecular stem-loop of U6,
      mutation G81C causes an allele-specific accumulation of U6 snRNP. Base pairing of
      the U6 3' stem-loop in yeast spliceosomes does not extend as far as to include
      the U6 sequence of U2-U6 helix Ib, in contrast to the human U6 3' stem-loop
      structure.

PMID- 12212857
TI  - Connexin 26 preverbal hearing impairment: mutation prevalence and heterozygosity
      in a selected population.
AB  - The objective of this investigation was to determine the prevalence of Cx26
      mutations in familial and sporadic cases of non-syndromic preverbal hearing
      impairment (HI). Molecular analysis of the Connexin 26 (Cx26/GJB2) gene was
      performed in 271 non-consanguineous individuals from the north of Italy, enrolled
      in the study because of the presence of non-syndromic preverbal sensorineural HI.
      One hundred and forty-six subjects (group 1) were referred from different ENT,
      paediatric and clinical genetic services, while 125 individuals (group 2)
      underwent Cx26 analysis based on precise anamnestic and clinical criteria for non
      syndromic HI and low risk of acquired deficit. All of the cases were also
      classified as familial or sporadic due to the presence or absence of other
      documented childhood HI in the family. Of the total 271 individuals, 36.9% were
      positive for Cx26 mutations: 37 belonged to group 1 and 63 to group 2, which
      delineates a statistically significant difference between the two groups. The
      difference is mainly attributable to sporadically occurring cases. No significant
      differences between group 1 and group 2 were found regarding the prevalence of
      the common 35delG variant and the number of unidentified putative Cx26 alleles,
      although these latter were shown to be higher in sporadically occurring cases of
      the unselected group 1. The difference observed in Cx26 prevalence can be
      explained by the clinical selection of group 2, which ensures minimum risk of
      including cases of acquired HI. In particular, in cases of sporadically occurring
      HI, the use of a defined protocol increases the chances of a positive molecular
      result, improving genetic counselling and the possibility of establishing better
      genotype-phenotype correlation. Our data raise questions about the possible
      interpretation of Cx26 heterozygosity in a selected population of hearing
      impaired individuals.

PMID- 12212858
TI  - The two faces of presbyacusis: hearing impairment and psychosocial consequences.
AB  - A study of hearing disability and handicap was performed in a sample of elderly
      persons living in an urban area of Goteborg, Sweden. The aim was to describe the
      psychosocial consequences of presbyacusis. For this purpose, elderly persons with
      fairly uncontaminated presbyacusis were chosen. The study group consisted of 154
      persons (59 men and 95 women) between the ages of 70 and 91 with a median age of
      78 years. The methods used included a self-assessed hearing instrument, pure-tone
      audiometry, and registration of desired services regarding rehabilitative
      audiology. The questionnaire included 26 items, 20 of them within four areas:
      assessment of normality, communication, quality of life and
      environment/orientation. The results showed that the assessment, whether the
      hearing was normal or not, was correlated with audiometrically measured hearing.
      Many of the participants expressed concern that their hearing had deteriorated.
      Communication situations with background noise were troublesome for many of the
      participants, but they had only minor problems when performing daily activities
      like shopping. The quality of life in general was only mildly affected by hearing
      loss. Items regarding environment and orientation showed varying results. Some
      everyday aspects of listening were related to hearing ability, but directional
      hearing was not correlated with measured hearing. In spite of the participants'
      worry about hearing deterioration, only 8% requested hearing aids as a result of
      the examination.

PMID- 12212859
TI  - Exploring the perceived world of the deaf-blind: on the development of an
      instrument.
AB  - In the present interview study on a sample of 13 deaf-blind participants (eight
      Usher patients and five with other diagnoses), all but one with some remaining
      visual function and all but two with a pure-tone average (PTA) exceeding 100 dB
      HL, an instrument was developed to assess discovery and localization abilities
      (DILO), compensatory use of sensory information, emotional and cognitive aspects
      of communication, and the preferred use of technical aids. Both qualitative and
      quantitative data were collected, and it was found that (1) the importance of
      early discovery of events and persons is rated high, (2) vision ranks higher than
      other sensory information, and airflow, smell and residual hearing come next in
      the perceptual world of this sample, (3) cognitive aspects of communication
      correlate with the importance of discovery and localization, and (4) technical
      aids dominated by vision and vibratory senses are preferred. It is concluded that
      even a small remaining visual function could be of significant importance in
      rehabilitation. Finally, in the deaf-blind group of subjects with some remaining
      visual function, utilization of remaining vision was felt to be more important
      than utilization of other sensory modalities.

PMID- 12212860
TI  - Effect of efferent-induced changes on acoustical reflex.
AB  - The efferent auditory pathway is known to alter the cochlear electrical
      properties, at low stimulus levels. This study aims to identify the effect of
      activation of the efferent auditory pathway through contralateral wide- and
      narrow-band noise at high sound levels. Acoustical reflex threshold and
      acoustical reflex amplitude (at ART + 10 dB) were obtained at three frequencies
      (500 Hz, 1 kHz, 2 kHz) in 60 normally hearing subjects, in the presence and
      absence of contralateral wide-and narrow-band noise (centred around reflex
      activating stimuli) at 30 dB SL. Results showed a consistent reduction in
      amplitude, and an increase in threshold, for 1- and 2-kHz tones in the presence
      of contralateral wideband but not narrow-band noise. Results are discussed with
      reference to the electrical properties of the cochlea, and the response
      properties of the efferent auditory pathway and cochlear nucleus.

PMID- 12212861
TI  - Relationship of intraoperative electrically evoked stapedius reflex thresholds to
      maximum comfortable loudness levels of children with cochlear implants.
AB  - Previous studies of the relationship between the intraoperatively obtained
      electrically evoked stapedius reflex threshold (ESRT) and the maximum comfortable
      loudness (MCL) values used to program the speech processor of cochlear implant
      (CI) patients have indicated that ESRTs provide an inexact estimate of MCL. In
      order to determine whether this estimate might be more exact for electrodes in
      different parts of the electrode array, we studied the electrode-specific
      relationships between ESRT and MCL in 29 Med-E1 Combi 40+ and 25 Nucleus CI 24 M
      patients after first fitting of the speech processor and 2 and 6 months later.
      The MCL values were mostly less than the ESRT values, but increased progressively
      over the first 6 months, reaching 83% and 72% of the ESRT values, on average,
      across all electrodes for the Med-E1 and Nucleus systems respectively. The
      population variation across electrodes decreased over the 6-month observation
      period and was least for the apical half of the array, for which the correlation
      coefficients of regressions between ESRT and MCL were around 0.65 for both
      systems. These results indicate that estimates of MCL values from the ERST are
      more accurate for the apical half of the intra-cochlear array and could then be
      described by an offset value plus an increase of MCL by 0.62 and 0.53 of ESRT for
      the Med-E1 and Nucleus systems, respectively.

PMID- 12212862
TI  - To seal or not to seal.

PMID- 12212863
TI  - The need for dental prophylaxis.

PMID- 12212864
TI  - The need for dental prophylaxis.

PMID- 12212865
TI  - The need for dental prophylaxis.

PMID- 12212866
TI  - The need for dental prophylaxis.

PMID- 12212867
TI  - The need for dental prophylaxis.

PMID- 12212868
TI  - Early childhood caries and well being.

PMID- 12212869
TI  - Project USAP 2000--use of sedative agents by pediatric dentists: a 15-year follow
      up survey.
AB  - PURPOSE: A national survey of members of the American Academy of Pediatric
      Dentistry was conducted to provide a 15-year update of information regarding the
      use of sedative agents by pediatric dentists. METHODS: All 3,315 active members
      of the Academy were sent questionnaires regarding the frequency of their use of
      sedation and 1,778 responded. Practitioners were questioned regarding their use
      of sedative agents and the nature of their patients receiving sedation. In
      addition, they were questioned in regard to their use of restraints and reasons
      for change in their use of sedation during the past two years. RESULTS: In regard
      to the use of nitrous oxide alone, 47% of practitioners responded that they use
      nitrous oxide less than 11% of the time. In regard to other types of sedative
      agents, most practitioners use little, if any, sedation. Eighty-two percent use
      sedation for less than 11% of their patients. Of the 1,778 respondents, 1,224
      used drugs other than nitrous oxide. In a typical three-month period, they
      performed 77,112 sedations. Of that number, 61,662 (80%) were administered by
      only 478 practitioners who use sedation on the average of once or greater each
      day. CONCLUSIONS: In comparison with previous surveys in 1985, 1991 and 1995,
      these results demonstrate an overall increased use of sedation by pediatric
      dentists. However, the increased use is due primarily to an increase in the
      numbers of practitioners who are heavier users of sedation (once or greater each
      day).

PMID- 12212870
TI  - Transient bacteremia induced by toothbrushing a comparison of the Sonicare
      toothbrush with a conventional toothbrush.
AB  - PURPOSE: Several investigations have demonstrated toothbrush-induced bacteremias.
      Transient bacteremias are well tolerated by healthy individuals but may increase
      endocarditis risk in patients with cardiac conditions. This study assessed
      bacteremia levels after brushing with either the Sonicare electric toothbrush or
      a manual toothbrush. METHODS: Fifty healthy children receiving dental treatment
      under general anesthesia with oral intubation were randomly assigned to a manual
      or Sonicare group. Plaque levels and gingival health were scored and a blood
      sample collected. Teeth were brushed for 1 minute and a postbrushing blood sample
      was drawn. Samples were analyzed for aerobic and anaerobic bacterial growth.
      RESULTS: Gingival health and plaque scores did not differ between groups. No
      correlation was detected between plaque and gingival scores and occurrence of
      bacteremia. The frequency of bacteremia was 46% with manual brushing: 18%
      aerobic, 9% anaerobic and 73% both. This differed significantly (P = .022) with
      78% bacteremias in the Sonicare group: 22% aerobic, 22% anaerobic and 56% both.
      CONCLUSIONS: The Sonicare induced significantly more bacteremias than manual
      toothbrushing. These results show that vigorous brushing increased bacteremia
      from one brushing but does not answer whether bacteremia incidence would decrease
      with a program of vigorous daily brushing; this should be clarified before
      recommending brushing methods for patients with compromised cardiac conditions.

PMID- 12212871
TI  - Perceived barriers and facilitators to dental treatment among female caregivers
      of children with and without HIV and their health care providers.
AB  - PURPOSE: This study sought to identify barriers and facilitators to dental care
      among families of predominately low socioeconomic status having children with and
      without HIV. METHODS: Twelve focus group sessions with African-American and
      Hispanic caregivers and 18 individual semistructured interviews with key
      informant health care providers were held at two sites: a hospital-based program
      (HBP) and a dental school-based program (DSBP), that provide pediatric dental
      services. SPSS Textsmart software was used to analyze qualitative data within and
      across group types and sites. RESULTS: Focus group participants (n = 72,
      averaging 6 women per group) included: HIV-seropositive biological mothers of HIV
      seropositive children (4 groups); HIV-seronegative caregivers of HIV-seropositive
      children (4 groups); and Medicaid-eligible, HIV-seronegative caregivers of HIV
      seronegative children (4 groups). The most commonly expressed barrier to dental
      care across groups was poor interpersonal communication between dental staff and
      caregiver/child. HIV-seronegative groups cited health care delivery system
      factors as barriers to receiving dental care more frequently than HIV
      seropositive caregivers who cited shame/anger and family illness as being more
      important. Common facilitators were positive communication and transportation
      assistance. Unique facilitators for HIV-seropositive groups were coordination of
      the dental visits with medical appointments at the HBP. Key informants
      acknowledged high stress in families having children with HIV/AIDS, cited dental
      fear among caregivers as a barrier to dental treatment adherence and reported
      that dental care seemed to be a low priority among many of these families.
      CONCLUSIONS: Facilitators and barriers to care included factors in the family,
      dental care and health care delivery systems as well as interpersonal
      communication between the dental providers and the families.

PMID- 12212872
TI  - Dental caries experience in a Connecticut Head Start program in 1991 and 1999.
AB  - PURPOSE: Reports from most industrialized countries suggest that dental caries in
      children has been declining over the last 50 years. However, this trend may be
      reversing, especially in younger children. The aim of the present study was to
      compare caries levels and patterns of 3- and 4-year-old Head Start children
      observed in 1999 with those observed in 1991. METHODS: Clinical dental caries
      data were collected from 517 children enrolled in the Hartford, Conn, Head Start
      program in 1999 and compared to similar data from 311 children attending the same
      Head Start program in 1991. No radiographs were used in either sample. RESULTS:
      In 1999, a mean dmft score of 1.49 and a caries prevalence of 38% was found
      compared to 1.68 and 49%, respectively, in 1991. When only those with caries were
      considered, both the mean dmft and mean dmfs were greater in 1999 than in 1991.
      In 1999, 57% of carious surfaces were treated compared to only 39% in 1991.
      Furthermore, this increased treatment was seen predominantly in those with
      greatest severity of disease. When the patterns of disease were analyzed,
      children in 1999 had greater levels and severity of maxillary anterior caries
      compared to 1991. No differences in pit and fissure caries and posterior proximal
      caries were observed. CONCLUSIONS: The overall prevalence of dental caries in the
      study population was less in 1999 than 1991, however, those with disease
      experienced a greater severity.

PMID- 12212873
TI  - Comparison of a computerized anesthesia device with a traditional syringe in
      preschool children.
AB  - PURPOSE: The purpose of this investigation was to evaluate the efficacy of a
      computerized injection device (Wand) on reducing pain behavior during injections
      with preschool-aged children. METHODS: Subjects consisted of 40 patients between
      the ages of 2 and 5 requiring local anesthesia for dental restorations in the
      maxilla. Patients were randomly assigned to either the Wand or the traditional
      anesthetic delivery system. A palatal approach to the anterior and middle
      superior alveolar nerves and the anterior superior alveolar nerve was used with
      the Wand injections. Buccal infiltration and palatal injections were used for the
      traditional method. Pain behavior was observed and coded. RESULTS: Results of
      Fisher Exact tests found that using the Wand to deliver anesthetic lead to
      significantly fewer (P < .01) disruptive behaviors in preschool-aged children
      when compared with a traditional injection regimen. In addition, none of the
      preschool-aged children exposed to the Wand required restraint during the initial
      interval, while nearly half of the children receiving a traditional injection
      required some type of immediate restraint. CONCLUSIONS: These results demonstrate
      that the Wand can significantly reduce disruptive behaviors in a population of
      young children who are traditionally more difficult to manage and may be one
      method of creating a more positive experience for the young child and the
      practitioner.

PMID- 12212874
TI  - Anthropometric finding in Nigerian children with sickle cell disease.
AB  - PURPOSE: Sickle cell disease (SCD) subjects have been widely reported to present
      with various anthropometric deficits, including malocclusion and stunting,
      compared to their unaffected peers. This study was carried out to examine these
      reports in Lagos. METHODS: A hospital-based cross-sectional study was carried out
      in 3 outpatient SCD units of one teaching and two general hospitals. All
      established SCD subjects aged 1 to 18 years (n = 177) were examined on
      consecutive clinic days. Controls (unaffected subjects; n = 122) were obtained
      from well-baby and surgical emergency clinics. Facial profile, occlusion, height,
      weight, head and mid-upper arm (MUA) circumference measurements were noted.
      RESULTS: A prognathic maxillary profile was found to be more prevalent in SCD
      subjects (21%) than controls (4%; P < .05). Class II malocclusion was found in
      21% of SCD subjects compared to 2% of controls (P < .05). The overall mean
      height, weight and head circumference of SCD subjects and controls were not
      significantly different (P > .05). However, at age 18 years, the weight of the
      SCD group was significantly less than that of the control group (P < .05). The
      mean MUA circumference was significantly higher in the control group (20.04 cm +/
      3.80) than in SCD subjects (17.91 cm +/- 2.96; P < .05). CONCLUSIONS: There was
      a higher prevalence of maxillary protrusion. and Class II malocclusion in SCD
      subjects than controls. Height and weight were not significantly different in
      both groups except at 18 years when SCD subjects weighed less than controls.

PMID- 12212875
TI  - Materials and techniques for restoration of primary molars by pediatric dentists
      in Florida.
AB  - PURPOSE: The purpose of this study was to obtain an overview of materials and
      techniques used by pediatric dentistry clinicians for posterior restorations in
      primary molars and to compare the results to what is being taught in dental
      schools. METHODS: A form with questions in different formats was mailed to all
      180 members of the American Academy of Pediatric Dentistry in Florida. The
      information requested included material selection for restorations in primary
      molars and the type of cavity preparation for amalgam and resin-based materials,
      and the bonding system in use. The response was anonymous, but information about
      gender and year of graduation for the clinicians was provided. RESULTS: Seventy
      percent of the clinicians responded to the survey. Resin-based materials were the
      most commonly selected for Class I and II restorations, while stainless steel
      crowns were the predominant material when 3 or more surfaces are involved. The
      slot-type of preparation was the most commonly used for tooth-colored
      restorations and the fifth generation ("one-bottle system") of bonding agents was
      the preferred adhesive system in use in primary molars. CONCLUSIONS: Different
      opinions were found between clinicians and educators in respect to material
      selection and contraindication criteria for the use of tooth-colored restorations
      in primary molars.

PMID- 12212876
TI  - A comparison of warmed and room-temperature anesthetic for local anesthesia in
      children.
AB  - PURPOSE: The purpose of this study was to assess children's reactions and record
      their sensations while receiving a warmed local anesthetic solution for dental
      procedures (37 degrees C; W) compared with one at room temperature (21 degrees C;
      RT). METHODS: Forty-four children between the ages of 6 to 11 (mean age = 7.9 +/-
      2.2 years) who were undergoing dental treatment participated in the study. A
      random crossover design was used. Each patient was randomly assigned to receive
      either a W or a RT local anesthesia on the first visit and the alternate local
      anesthesia on the second visit. During the injection, the modified Behavioral
      Pain Scale (BPS) was used. For subjective evaluation, the Wong-Baker FACES Pain
      Rating Scale (FPS) and the Visual Analogue Scale (VAS) were used. RESULTS: No
      significant difference was found between the W or RT local anesthesia when used
      during the first or second visit. In all parameters, children's reactions to both
      types of injection were similar, with no statistically significant difference.
      Using the FPS, 19 boys (91%) ranked the experience of local anesthesia as a
      positive experience (0 to 2 in the scale) while 4 boys (9%) ranked the same
      experience as negative. This was true for both types (W and RT). All 21 girls who
      participated in the study ranked the local anesthesia experience using the FPS as
      a positive experience (0 to 2 in the scale). No significant difference was found
      in the mean VAS scores between the room-temperature group and the warm group
      (23.4 +/- 21.8 and 20.8 +/- 18.9, respectively). CONCLUSIONS: There is no
      advantage to warming local anesthetic solution prior to injection.

PMID- 12212877
TI  - Mucosal calcified nodule of the gingiva in an infant.
AB  - The mucosal calcified nodule is a rare oral lesion that has a predilection for
      the young child. This case report describes an infant with a persistent and
      tender gingival swelling associated with an unerupted, maxillary central incisor.
      Besides a differential diagnosis for this entity, the causes of abnormal calcium
      deposits within the skin of children are discussed.

PMID- 12212878
TI  - Delivering supplemental oxygen during sedation via a saliva ejector.
AB  - Intraoperative oxygen supplementation to sedated children has been shown to
      prevent hemoglobin desaturations even in the presence of apnea during pediatric
      conscious sedation. Although many practitioners deliver supplemental oxygen via a
      nasal hood, this method is impractical and often unsuccessful if the child is a
      mouth breather, has moderate adenotonsillar hypertrophy or occasionally cries
      during treatment (at which time there will be mouth breathing). This paper
      describes a method in which the saliva ejector is used to deliver supplemental
      oxygen to sedated children while they are receiving dental treatment. The
      advantages of this method and suggestions for its successful application are also
      included.

PMID- 12212879
TI  - Dental management of a pediatric patient with mastocytosis: a case report.
AB  - Mastocytosis is a heterogeneous group of clinical disorders characterized by an
      excessive number of normal mast cells in a variety of tissues (skin, bone marrow,
      liver, spleen and lymph nodes). It is most often seen in the skin in pediatric
      onset mastocytosis presenting as urticaria pigmentosa. Children with this
      disorder are on a strict avoidance protocol of triggering factors to decrease the
      likelihood of life-threatening anaphylactic reactions. Close monitoring and the
      avoidance of known histamine-releasing drugs is necessary in the pediatric dental
      office, as is a readiness to use resuscitative measures. A case of a 4-year, 6
      month-old pediatric dental patient with mastocytosis is presented. Dental
      treatment was provided in an ambulatory setting utilizing nitrous oxide, oxygen
      analgesia and H1 and H2 antihistamines to prevent mast cell degranulation and to
      provide sedation.

PMID- 12212880
TI  - Evaluation of aggressive pulp therapy in a population of vitamin D-resistant
      rickets patients: a follow-up of 4 cases.
AB  - This investigation collected clinical and radiographic data from a retrospective
      chart review of 4 patients receiving prophylactic formocresol pulpotomies and
      stainless steel crowns following a dental abscess associated with a medical
      diagnosis of vitamin-D resistant rickets (VDRR) at Texas Scottish Rite Hospital
      for Children in Dallas, Tex. Clinical and radiographic data were available for 29
      primary teeth in 4 children, with follow-up times ranging from 2 years, 1 month
      to 5 years, 6 months. Based on available recalls of 29 teeth treated following
      the prophylactic formocresol pulpotomy, 22 failed clinically. The earliest
      failure occurred at 3 months; the longest time to failure was 3 years, 9 months.
      No trends were discernable between tooth type and failure rate, although the
      shorter the time between eruption of the tooth and pulpotomy treatment, the
      greater the chance of success. Presently, there is not enough evidence to suggest
      that prophylactic pulpotomy therapy in VDRR patients is beneficial in preserving
      their primary dentition.

PMID- 12212881
TI  - In vivo dental plaque pH variation with regular and diet soft drinks.
AB  - PURPOSE: Despite the presence or absence of artificial sweeteners in cola drinks,
      both regular and diet soft drinks still contain phosphoric and citric acid, which
      contributes to the total acidic challenge potential on enamel. The purpose of
      this study was to assess the plaque pH, in vivo, after a substrate challenge of
      diet and regular soft drinks. METHODS: Seventeen subjects were recruited for this
      study. All subjects were between the ages of 12 and 15 and had at least 4
      restored tooth surfaces present. The subjects were given consent by their parents
      and were asked to refrain from brushing for 48 hours prior to the study. At
      baseline, plaque pH was measured from 4 separate locations using touch electrode
      methodology. Each subject was then randomly assigned to one of two groups. The
      first group was exposed to regular Coke followed by Diet Coke, while the second
      group was exposed to Diet Coke followed by regular Coke. Subjects were asked to
      swish with 15 ml of the respective soft drink for one minute. Plaque pH was
      measured at the 4 designated tooth sites at 5-, 10- and 20-minute intervals.
      Subjects then repeated the experiment using the other soft drink. RESULTS: The
      results showed that regular Coke had significantly more acidic plaque pH values
      at the 5-, 10- and 20-minute intervals compared to Diet Coke, (P = < .001), when
      subjected to a t test. The mean pH at 5 minutes for Coke and Diet Coke was 5.5 +/
      0.5 and 6.0 +/- 0.7, respectively. At 10 minutes, the pH for Coke and Diet Coke
      was 5.6 +/- 0.6 and 6.2 +/- 0.7, respectively. The pH at 20 minutes for Coke and
      Diet Coke was 5.7 +/- 0.7 and 6.5 +/- 0.5, respectively. CONCLUSIONS: These data
      suggest that regular Coke possesses a greater acid challenge potential on enamel
      than Diet Coke. However, in this clinical trial, the pH associated with either
      soft drink did not reach the critical pH which is expected for enamel
      demineralization and dissolution.

PMID- 12212882
TI  - Protamine P1 sequences in equids: comparison with even-toed animals.
AB  - Protamine P1 amino acid sequences were determined from semen samples of the
      Przewalski horse, donkey, Somali wild ass, Grevy's zebra, and Grant's zebra (odd
      toed perissodactyls), and compared with those of the domestic horse. Although the
      rate of amino acid variation of protamine P1 is known to be among the most
      rapidly diverging polypeptides, the equid sequences revealed only little
      variation. The sequence from the Przewalski horse was identical with that from
      the domestic horse. The other sequences differed from the corresponding sequences
      of the domestic and Przewalski horses in two positions-Ser29 was replaced by Cys
      and Gln32 was replaced by Arg. The presence of the Cys residue at position 29 in
      the protamine P1 from the zebras, the donkey, and the Somali wild ass may allow
      formation of one extra protamine disulfide bridge during chromosome condensation
      in these species. Comparison with protamines from various even-toed animals
      (artiodactyls) indicated amino acid changes specific for those but different from
      the equid sequences.

PMID- 12212883
TI  - Effect of nitric oxide synthase inhabitors on ovulation in hCG-stimulated mares.
AB  - Recent studies suggest that nitric oxide (NO) may have a role in regulating
      ovarian physiology. To investigate the role of NO during ovulation in mares,
      inhibitors of the nitric oxide synthase (NOS) were administered to estrous mares.
      Forty cycling mares (20 horses and 20 pony mares) were allotted to one of the
      three treatment groups. Once a follicle was at least 27 mm in diameter, but
      smaller than 35 mm, mares were given one of the following treatments: saline
      solution 0.9% (n = 20, w/v, i.v., every 12 h), Nomega-nitro-L-arginine methyl
      ester hydrochloride (L-NAME; n = 10, 148 micromol/kg, i.v., every 12 h), or
      aminoguanidine hemisulfate (AG; n = 10, 406 micromol/kg, i.v., every 12 h). When
      a follicle >30 mm was present on one of the ovaries, ovulation was induced with
      hCG (2,500 IU, i.v.). The median time of ovulation (+/-6 h) after hCG
      administration for the treatment groups was 42, 84 and 54 h for mares treated
      with saline solution, L-NAME and AG, respectively. There was no significant
      difference between the groups treated with AG or L-NAME (P = 0.06); however,
      these groups were different from the control group (P < 0.05). The delayed
      ovulation caused by the administration of NOS inhibitors suggests a role for NO
      in follicular growth and ovulation in horses.

PMID- 12212884
TI  - Migration of bovine spermatozoa in a synthetic medium and its relation to in vivo
      bull fertility.
AB  - Although sperm migration has been extensively refined and validated in human
      infertility studies, its application to predict bovine fertility has been very
      limited, and a clear relation between the sperm migration distance and in vivo
      bull fertility has never been demonstrated. A synthetic medium based upon methyl
      cellulose (MC) was tested for its suitability to serve as a migration medium for
      frozen-thawed bovine spermatozoa. The effects of the concentration of MC, the
      incubation time, and sperm concentration on sperm migration capacity was
      determined. The relation between sperm migration capacity at different incubation
      times of the frozen-thawed spermatozoa of five bulls, and their 56 days nonreturn
      rates (NRRs) was assessed in order to evaluate its suitability as a tool to
      predict in vivo bull fertility. The highest repeatability of the sperm migration
      test (CV = 10.7%) was obtained when the sperm migration distance of the five
      vanguard motile spermatozoa was determined at 30 min incubation at 37 degrees C
      in a migration medium with 1.35% MC. No significant difference in migration
      distance was demonstrated when sperm concentrations of 100 x 10(6) and 150 x
      10(6) spermatozoa/ml, respectively, were used. Despite the relatively high
      repeatability of the migration test, no relation was found between the sperm
      migration distance and the 56 days NRRs of five sire bulls. Therefore, the sperm
      migration test in 1.35% MC cannot be used to predict in vivo bull fertility
      accurately.

PMID- 12212885
TI  - The effect of lutalyse on the training of sexually inexperienced boars for semen
      collection.
AB  - The objective was to determine if i.m. treatments of lutalyse (PGF2alpha;
      dinoprost tromethamine salt) expedited the training of sexually inexperienced
      boars for semen collection. Lean-type, terminal-line boars (n = 40; 177.4 +/- 2.4
      day of age and 112.8 +/- 2.0 kg body weight) that had not previously experienced
      natural mating were utilized. Boars were moved individually twice weekly for 6
      weeks (total of 12 training sessions) to a semen collection room equipped with an
      artificial sow. Upon entering the semen collection room, boars received i.m.
      treatments of either deionized water (4 ml, n = 10) or lutalyse at doses of 5 mg
      (n = 10), 10 mg (n = 10), or 20 mg (n = 10), and subsequently received a libido
      score of 1-5 (1 = no interest in the artificial sow; 5 = mounting artificial sow
      and allowing semen collection). The percentages of boars successfully trained for
      semen collection during the experimental period were similar (P > 0.05) for
      controls (20%) and boars receiving 5 mg (30%), 10 mg (20%), or 20 mg (10%) of
      lutalyse. Average libido score for boars receiving 10 mg lutalyse (2.35 +/- 0.08)
      was greater (P < 0.05) than for controls (2.14 +/- 0.06). In summary, lutalyse
      increased libido scores, but did not affect the number of boars trained for semen
      collection.

PMID- 12212886
TI  - Ultrasonic measurements of second and third trimester fetuses to predict
      gestational age and date of parturition in captive and wild spotted hyenas
      Crocuta crocuta.
AB  - Parturition in spotted hyenas (Crocuta crocuta) is a fascinating event to
      witness, as females of this species are highly masculinized and give birth
      through a penis-like clitoris. Furthermore, shortly after birth, a high rate of
      aggression occurs between littermates that can sometimes end in siblicide. To
      study these events thoroughly, an accurate estimate of the date of parturition is
      necessary. To this end, we performed transabdominal ultrasounds every 20-30 days
      in five captive spotted hyenas of known gestational age, beginning approximately
      30 days after mating. We measured the femur length (FL), abdominal circumference
      (AC), and biparietal diameter (BPD) of eight fetuses from Days 42 to 100 of their
      110 days of gestation. FL proved to be the most effective measurement, as it
      correlated well with gestational age and was easy to obtain consistently. The
      relationship between estimated gestational age (EGA) and FL is described by the
      equation: [EGA = 37.3 + (14.0 x FL)]. AC also correlated well with EGA, but was
      more difficult to measure than FL. Measuring BPD became increasingly difficult as
      pregnancies advanced beyond 70 days of gestation. Because gestational age is
      often not known in captive and free-ranging spotted hyenas, measuring fetal FL
      ultrasonographically is a rapid and reliable way to determine an approximate date
      of parturition. This technique proved invaluable when used to track and monitor a
      free-ranging spotted hyena during the days just before and after parturition.

PMID- 12212887
TI  - Removal of deslorelin (Ovuplant) implant 48 h after administration results in
      normal interovulatory intervals in mares.
AB  - Deslorelin implants, approved for use in inducing ovulation in mares, have been
      associated with prolonged interovulatory intervals in some mares. Administration
      of prostaglandins in the diestrous period, following a deslorelin-induced
      ovulation, has been reported to increase the incidence of delayed ovulations. The
      goals of the present study were: (1) to determine the percentage of mares given
      deslorelin that experience delayed ovulations with or without subsequent
      prostaglandin treatment, and (2) to determine if removal of the implant 48 h
      after administration would effect the interval to subsequent ovulation. We
      considered interovulatory intervals to be prolonged if they were greater than the
      mean +/- 2 standard deviation (S.D.) of the control group in study 1 and the hCG
      group in study 2. In study 1, we retrospectively reviewed reproduction records
      for 278 mares. We either allowed the mare to ovulate spontaneously or induced
      ovulation using deslorelin acetate implants or hCG. We administered prostaglandin
      intramuscularly, 5-9 days after ovulation in selected mares in each group. A
      higher percentage of mares which were induced to ovulate with deslorelin and
      given prostaglandins had a prolonged interovulatory interval (23.5%; n = 16), as
      compared to deslorelin-treated mares that did not receive prostaglandins (11.1%;
      n = 5). In study 2, we induced ovulation in mares with hCG (n = 47), a
      subcutaneous deslorelin implant via an implanting device provided by the
      manufacturer (n = 28), or a deslorelin implant via an incision in the neck (n =
      43) and we removed the implant 48 h after administration. We administered
      prostaglandin to all mares 5-9 days after ovulation. In study 2, mares from which
      the implant was removed had a normal ovulation rate and none had a prolonged
      interval to ovulation. Administration of prostaglandin after deslorelin treatment
      was associated with a longer interval from luteolysis to ovulation than that
      found in mares not treated with deslorelin. Prostaglandin administration during
      diestrus may have exacerbated the increased interval to ovulation in deslorelin
      treated mares. We hypothesize that prolonged secretion of deslorelin from the
      implant was responsible for the extended interovulatory intervals.

PMID- 12212888
TI  - Relationship between antral follicle size, oocyte diameters and nuclear
      maturation of immature oocytes in pigs.
AB  - We designed the present study to examine the possible relationship between
      oocyte, antral follicle size and the nuclear heterogeneity of immature pig
      oocytes, in order to study the heterogeneity of oocyte populations in ovaries
      obtained from slaughterhouses. Previously, we carried out an initial experiment
      to determine, by histological analysis, the effectiveness of the macroscopic
      criteria (MC) used to screen atretic and nonatretic antral follicles. We
      recovered 239 follicles by mechanical dissection, measured them with a
      computerized image analysis system, and classified them into five size categories
      according to their diameter (FD): Group 1 (0.40-0.99 mm), Group 2 (1.00-2.19 mm),
      Group 3 (2.20-2.79 mm), Group 4 (2.80-3.59 mm) and Group 5 (3.60-6.50 mm). In
      relation to histological analysis, the results showed that MC is an effective
      method to select atretic and nonatretic antral follicles from 0.40 to 6.50 mm in
      diameter (overall accuracy was 80.75%, with sensitivity and specificity rates of
      79.33 and 82.20%, respectively). In a second experiment, we recovered 454
      nonatretic follicles, then measured and classified them as mentioned above. We
      removed oocytes individually from follicles and measured their size (oocyte
      diameter without and with zona pellucida, OD and TOD, respectively). Finally, we
      evaluated the relationship between OD, FD and nuclear maturation of immature
      oocytes (germinal vesicles (GV) Stages 0, I, II, III and IV; diakinesis, prophase
      I, and metaphase I). Overall OD was 101.77 +/- 0.65, 109.19 +/- 0.45, 113.55 +/-
      0.50, 116.92 +/- 0.46 and 117.13 +/- 0.47 microm (Groups 1, 2, 3, 4, and 5,
      respectively). Differences in OD between groups were significant (P < 0.01),
      although from 2.80 to 6.50 mm follicles, the oocytes were not different in size.
      There was a certain heterogeneity in OD within each follicular group. Although we
      observed a certain degree of nuclear variability, regardless of FD or OD, the
      present study showed a clear progression in GV when FD increased from 0.40 to
      6.50 mm. A positive correlation (r2 = 0.4248; P > 0.05) was established mainly
      between the nuclear stage and oocyte diameter.

PMID- 12212889
TI  - Aberrations in uterine contractile patterns in mares with delayed uterine
      clearance after administration of detomidine and oxytocin.
AB  - An experiment was conducted to determine whether the uterotonic effects of
      oxytocin, a drug used to treat mares that have a delay in uterine clearance were
      affected by the sedative detomidine (an alpha2-agonist), a drug used to treat
      fractious mares. An additional objective was to identify propagation patterns of
      uterine contractions and determine whether these patterns differed between normal
      mares and mares with delayed uterine clearance (DUC). Intrauterine pressure was
      measured in five reproductively normal mares and four mares with DUC during
      estrus using an 8-F Milar catheter with two discrete pressure sensors. Mares
      received one of three treatments in random order: detomidine (0.001 mg/kg; i.v.);
      detomidine followed in 10 min by oxytocin (10 IU; i.v.); and saline (0.9% NaCl
      0.5 ml; i.v.) followed in 10 min by oxytocin. All treatments induced waves of
      contractions; however, only three mares with DUC exhibited contractions after
      administration of detomidine. Normal mares experienced more uterine contractions
      (P < 0.01) that tended to last longer (P < 0.06), and were of greater intensity
      (P < 0.04) than mares with delayed clearance. Administration of detomidine before
      oxytocin increased the number of contractions (P < 0.02) and increased the
      maximum intrauterine pressure in the uterine horn (P < 0.05) in normal mares as
      compared to response after administration of saline and oxytocin. Detomidine had
      no effect in mares with delayed clearance. All mares had more propagating than
      non-propagating uterine contractions (74 +/- 8 versus 25 +/- 8%, respectively).
      Normal mares exhibited a normal propagation pattern more frequently (P < 0.0001)
      than mares with DUC. Simultaneous (P < 0.05) and inverted (P < 0.03) contractions
      occurred more frequently in mares with DUC. Administration of detomidine
      increased the number (P < 0.01), and tended to increase the percentage (P < 0.07)
      of normal propagating uterine contractions in normal mares, but did not affect
      propagation patterns in mares with DUC. In conclusion, detomidine augmented the
      uterotonic effect of oxytocin in normal mares but not in mares with DUC. Data
      suggest that mares with DUC have a defect in myoelectrical signaling and a
      decrease in the contractile strength of the uterine muscle.

PMID- 12212890
TI  - The effect of an acute energy deficit on the hormone profile of dominant
      follicles in dairy cows.
AB  - The effect of an acute energy deficit on the hormone balance of dominant
      follicles was studied in six normally-cycling, high-yielding Italian Friesian
      cows at 60 and 90 days after calving. At 60 days after calving, the cows, which
      had been fed according to their maintenance and production requirements, were
      synchronized and follicular fluid was collected from the dominant follicles under
      ultrasound guidance. At 90 days after calving, the same protocol was used on the
      same cows, which had been subjected to an acute dietary restriction since the day
      of the second prostaglandin treatment for synchronization. At the follicular
      level, the dietary restriction caused a significant reduction (P < 0.05) in the
      concentration of estradiol-17beta and a significant increase (P < 0.05) in NEFA.
      There were no significant differences in follicular diameter, follicular
      concentrations of progesterone, and Insulin-like Growth Factor-I (IGF-I). The
      amount of IGFBP2 and IGFBP3 in follicular fluid increased. The results suggest
      that an acute dietary restriction induces substantial changes at the dominant
      follicle level, despite the fact that the recruitment and selection phase
      occurred before the cows' diet was restricted.

PMID- 12212891
TI  - Pregnancies from vitrified equine oocytes collected from super-stimulated and non
      stimulated mares.
AB  - The objectives were to compare embryo development rates after transfer into
      inseminated recipients, vitrified thawed oocytes collected from super-stimulated
      versus non-stimulated mares. In vivo matured oocytes were collected by
      transvaginal, ultrasound guided follicular aspiration from super-stimulated and
      non-stimulated mares 24-26 h after administration of hCG. Oocytes were cultured
      for 2-4 h prior to vitrification. Cryoprotectants were loaded in three steps
      before oocytes were placed onto a 0.5-0.7 mm diameter nylon cryoloop and plunged
      directly into liquid nitrogen. Oocytes were thawed and the cryoprotectant was
      removed in three steps. After thawing, oocytes were cultured 10-12 h before
      transfer into inseminated recipients. Non-vitrified oocytes, cultured 14-16 h
      before transfer, were used as controls. More oocytes were collected from 23 non
      stimulated mares (20 of 29 follicles), than 10 super-stimulated mares (18 of 88
      follicles; P < 0.001). Of the 20 oocytes collected from non-stimulated mares, 12
      were vitrified and 8 were transferred as controls. After thawing, 10 of the 12
      oocytes were morphologically intact and transferred into recipients resulting in
      one embryonic vesicle on Day 16 (1 of 12 = 8%). Fourteen oocytes from super
      stimulated mares were vitrified, and 4 were transferred as controls. After
      thawing, 9 of the 14 oocytes were morphologically intact and transferred into
      recipients resulting in two embryonic vesicles on Day 16 (2 of 14 = 14%). In
      control transfers, 7 of 8 oocytes from non-stimulated mares and 3 of 4 oocytes
      from super-stimulated mares resulted in embryonic vesicles on Day 16. The two
      pregnancies from vitrified oocytes resulted in healthy foals.

PMID- 12212892
TI  - Sexual development of dairy bulls in the Mexican tropics.
AB  - Sexual development and pubertal traits were studied in Holstein Frisian (Ho) and
      Brown Swiss (BS) bulls born and maintained under tropical conditions.
      Characteristics evaluated every 2 weeks, from 27 to 63 weeks of age, included
      live weight, scrotal circumference, testicular diameter, semen quality and sexual
      behavior. Puberty was defined as the age at which a bull first produced an
      ejaculate containing at least 50 x 106 spermatozoa, with a minimum of 10%
      progressive motility. Testicular growth was linear in Ho bulls and quadratic in
      BS bulls. There was no breed difference in age at puberty (Ho, 333 +/- 15.8 days;
      BS, 311 +/- 10.5 days). However, at puberty, live weight and scrotal
      circumference tended to be greater in Ho (276 +/- 16.9 kg and 28.4 +/- 1 cm,
      respectively) than in BS bulls (233 +/- 11.3 kg and 25.9 +/- 0.7 cm,
      respectively), and testicular diameter was larger for Ho (5.5 +/- 0.24 cm) than
      for BS bulls (4.8 +/- 0.16 cm). Pooled data for all bulls for semen
      characteristics at puberty were: volume, 6.3 +/- 0.6 ml; progressive motility,
      26.8 +/- 4.4%; sperm concentration, 58.5 +/- 13.9 x 10(6) spermatozoa/ml, and
      351.5 +/- 91.2 x 10(6) spermatozoa/ejaculate. These values improved until at
      least 18 weeks after puberty. Eighty-five percent of bulls mounted heifers by 206
      days of age, but only a few bulls had mounts with ejaculation during the study.
      It was concluded that reproductive development was similar between Ho and BS
      bulls, but slower than that reported for dairy bulls in temperate areas.
      Variation in some characteristics, such as scrotal circumference, was observed
      among bulls within each breed group, which might be of benefit for genetic
      selection.

PMID- 12212893
TI  - Fetal infection with Neospora caninum in dairy and beef cattle in Belgium.
AB  - Neospora caninum is a protozoan parasite, which causes fetal and neonatal
      mortality in livestock and companion animals. In 224 abortions in Belgian cattle,
      different diagnostic methods were used to demonstrate infection, and the presence
      of N. caninum. An indirect fluorescent antibody test (IFAT) was used to analyze
      fetal and maternal sera and immunohistochemistry (IHC) was performed when lesions
      consistent with neosporosis were observed in the brain, heart or liver. Twenty
      dairy cattle sera out of 70 (29%) and 13 beef cattle sera out of 93 (14%) were
      positive by IFAT. A positive titer to N. caninum was found in seven and three
      fetuses born to beef and dairy cows, respectively. Lesions consistent with N.
      caninum infection were observed in 17 fetuses. Of nine positive beef fetuses,
      five were confirmed by IHC while, all but one dairy fetus were confirmed using
      the same technique. Age had no influence on the serological status of the mother
      (P = 0.486) whereas husbandry system had a borderline influence (P = 0.082).
      However, a strong association (P = 0.004) between the level of antibodies in the
      dam and the occurrence of lesions in the fetus was observed and lesions were more
      prominent in dairy than in beef fetuses. Additionally, the distribution of intra
      cerebral lesions was more extensive in dairy than in beef fetuses (P < 0.0001).
      Age and serological status of the fetus were found to influence the occurrence of
      lesions in beef fetuses (both P < 0.001) but no such significant relationships
      could be demonstrated in dairy fetuses. The study indicated that N. caninum must
      be considered as an important cause of bovine abortion in Belgium.

PMID- 12212894
TI  - Breeding soundness evaluations of 3,648 yearling beef bulls using the 1993
      Society for Theriogenology guidelines.
AB  - Our objective was to perform a retrospective analysis of breeding soundness
      evaluations (BSEs) as classified by the 1993 Society for Theriogenology (SFT)
      guidelines [Chenoweth et al., Guidelines for using the bull breeding soundness
      evaluation form, in: Theriogenology Handbook, 1993, pp. B-10]. Data included BSE
      information obtained from five performance-testing stations in South Carolina
      (SC1, SC2, SC3) and Tennessee (TN1, TN2) from 1986 through 1999 on 3648 Angus,
      Brangus, Charolais, Chianina, Gelbvieh, Limousin, Polled Hereford, Santa
      Gertrudis, Simbrah, and Simmental bulls. Analyses were simplified by classifying
      all bulls as either satisfactory or unsatisfactory potential breeders. Of the
      3648 bulls evaluated, 76.2% were classified as satisfactory potential breeders.
      Of all bulls evaluated, 4.0% were unsatisfactory due to inadequate spermatozoal
      motility, 7.0% due to inadequate spermatozoal morphology and 2.6% due to a
      combination of inadequate motility and morphology. Unsatisfactory classifications
      due to non-spermatozoal parameters out of all bulls were 10.2%, with 7.1% for
      inadequate scrotal circumference and 3.1% for physical abnormalities. For
      satisfactory and unsatisfactory bulls, respectively, means and standard
      deviations were 35.8 +/- 2.7 and 33.0 +/- 4.1 cm (P < 0.001) for scrotal
      circumference, 63 +/- 18 and 35 +/- 24% (P < 0.001) for percent motility, and 86
      +/- 7 and 63 +/- 21% (P < 0.001) for percent normal morphology.

PMID- 12212895
TI  - Pregnancy rates after transfer of frozen bovine embryos: a field trial.
AB  - An efficient and practical technique for bovine embryo cryopreservation is a
      fundamental issue in the widespread use of embryo transfer. The present study
      shows results obtained in field experiments. In the first experiment, two slow
      freezing methods using glycerol and a one-step method using ethylene glycol were
      compared: glycerol added in two steps (5 and then 10%), glycerol added in one
      step (10%) and 1.5 M ethylene glycol with direct transfer. The three methods were
      equally effective; pregnancy rates of 40.4, 39.1 and 45.4%, respectively were
      achieved. In the second experiment, using 1.5 M ethylene glycol with direct
      transfer, 20 and 5 min of equilibration of the cryoprotectant were tested. There
      were no observed significant differences in pregnancy rates. In the third
      experiment, ethylene glycol and propylene glycol were combined with three sucrose
      concentrations (0, 0.1 or 0.3 M) in a one-step method. It was observed that
      ethylene glycol and 0.1 M sucrose yielded the highest pregnancy rate, not
      differing from fresh controls. Similar pregnancy rates were noted after using
      multiple-step or one-step methods, but the one-step method is preferable due to
      its simplicity and applicability to field conditions.

PMID- 12212896
TI  - Morphology and morphometry of in vivo- and in vitro-produced bovine concepti from
      early pregnancy to term and association with high birth weights.
AB  - This study was designed to characterize conceptus development based on pre- and
      postnatal measurements of in vivo- and in vitro-derived bovine pregnancies. In
      vivo-produced embryos were obtained after superovulation, whereas in vitro
      produced embryos were derived from established procedures for bovine IVM, IVF and
      IVC. Blastocysts were transferred to recipients to obtain pregnancies of single
      (in vivo/singleton or in vitro/singleton groups) or twin fetuses (in vitro/twins
      group). Ultrasonographic examinations were performed weekly, from Day 30 of
      gestation through term. Videotaped images were digitized, and still-frames were
      used for the measurement of conceptus traits. Calves and fetal membranes (FM)
      were examined and measured upon delivery. In vitro-produced fetuses were smaller
      than in vivo controls (P < 0.05) during early pregnancy (Day 37 to Day 58), but
      in vitro/singletons presented significantly higher weights at birth than in
      vivo/control and in vitro/twin calves (P < 0.05). From late first trimester of
      pregnancy (Day 72 to Day 93), placentomes surrounding in vitro-derived singleton
      fetuses were longer and thinner than controls (P < 0.05). At term, the presence
      of giant cotyledons in the fetal membranes in the in vitro group was associated
      with a larger cotyledonary surface area in the fetal horn (P < 0.05). The
      biphasic growth pattern seen in in vitro-produced pregnancies was characterized
      by conceptus growth retardation during early pregnancy, followed by changes in
      the development of the placental tissue. Resulting high birth weights may be a
      consequence of aberrant placental development due to the disruption of the
      placental restraint on fetal growth toward the end of pregnancy.

PMID- 12212897
TI  - Penetration in vitro of zona-free pig oocytes by homologous and heterologous
      spermatozoa.
AB  - We examined the penetrability of pig, rat and bull spermatozoa into zona-free pig
      oocytes. Frozen-thawed boar spermatozoa penetrated into both zona-intact and zona
      free oocytes with similar efficacy in a modified Tris-buffered medium (mTBM)
      supplemented with BSA and caffeine, but not in medium without caffeine. Rat
      epididymal spermatozoa did not readily penetrate into zona-free pig oocytes in
      mTBM with BSA. However, when a modified Krebs-Ringer bicarbonate solution was
      used, penetration rate varied with sperm concentrations at insemination: 79% of
      the oocytes were penetrated at 1.0 x 10(6) cells/ml, but very few at 0.1 x 10(6)
      and 10.0 x 10(6) cells/ml. In all oocytes penetrated, no activation was observed
      and the sperm nucleus was fully decondensed but did not transform into a male
      pronucleus. Frozen-thawed bull spermatozoa were also found to penetrate into zona
      free pig oocytes in mTBM with BSA, caffeine and heparin: higher penetration rates
      were obtained with 1.0 x 106 and 10.0 x 10(6) spermatozoa/ml compared with 0.1 x
      10(6) spermatozoa/ml. The penetration rate with 1.0 x 10(6) spermatozoa/ml was
      stable in five different bulls. All oocytes penetrated were activated and male
      pronuclear formation was observed in 57-79% of the penetrated oocytes. These
      results suggest that capacitation or the acrosome reaction is required for boar,
      rat, and possibly, bull spermatozoa to penetrate into zona-free pig oocytes. Bull
      spermatozoa can easily induce activation of pig oocytes and form male pronuclei,
      but rat spermatozoa cannot do so, indicating species differences in the ability
      of spermatozoa to activate pig oocytes and to transform to male pronuclei in the
      ooplasm.

PMID- 12212898
TI  - Calibration of neutron albedo dosemeters.
AB  - It is shown that by calibrating neutron albedo dosemeters under the proper
      conditions, two complicating effects will essentially cancel out, allowing
      accurate calibrations with no need for explicit corrections. The 'proper
      conditions' are: a large room (> or = 8 m on a side). use of a D2O moderated
      252Cf source, and a source-to-phantom calibration distance of approximately 70
      cm.

PMID- 12212899
TI  - On the need for guidance regarding extremity dosimetry.

PMID- 12212900
TI  - Measurement of neutron dose with an organic liquid scintillator coupled with a
      spectrum weight function.
AB  - A dose evaluation method for neutrons in the energy range of a few MeV to 100 MeV
      has been developed using a spectrum weight function (G-function), which is
      applied to an organic liquid scintillator of 12.7 cm in diameter and 12.7 cm in
      length. The G-function that converts the pulse height spectrum of the
      scintillator into the ambient dose equivalent, H*(10), was calculated by an
      unfolding method using successive approximation of the response function of the
      scintillator and the ambient dose equivalent per unit neutron fluence (H*(10)
      conversion coefficients) of ICRP 74. To verify the response function of the
      scintillator and the value of H*(10) evaluated by the G-function. pulse height
      spectra of the scintillator were measured in some different neutron fields, which
      have continuous energy, monoenergetic and quasi-monoenergetic spectra. Values of
      H*(10) estimated using the G-function and pulse height spectra of the
      scintillator were compared with those calculated using neutron energy spectra.
      These doses agreed with each other. From the results, it was concluded that
      H*(10) can be evaluated directly from the pulse height spectrum of the
      scintillator by applying the G-function proposed in this study.

PMID- 12212901
TI  - Artefacts of electron paramagnetic resonance dosimetry caused by a mechanical
      effect on samples of tooth enamel.
AB  - It has been ascertained that in the process of the mechanical preparation of
      tooth enamel, two types of paramagnetic centres are formed. The centres of one
      type, the long-lived ones, occurred in the process of friction of dental borers
      against the enamel. Their number grew with an increase of the treated surface
      area and the rotation rate of the borers. The electron paramagnetic resonance
      signal of such radicals looked like a symmetric singlet with the width
      deltaHpp=0.094 mT and g=2.0029. The other, short-lived centres, occurred when
      tooth enamel was crushed into small granules, which caused an increase in the
      background signal intensity. The mechanism of formation of paramagnetic centres
      in enamel during the process of teeth treatment and prepartion has been
      considered. The estimation of an increase in the reconstructed absorbed dose due
      to the contribution from the mechanically induced signal has been made.
      Contamination of tooth enamel samples with diamond crumb during diamond borer
      preparation has been shown to lead to an imaginary increase in radiation-induced
      signal intensity and, consequently, to an increase in the reconstructed dose.

PMID- 12212902
TI  - Measurement of lineal-energy distributions for neutrons of 8 keV to 65 MeV by
      using a tissue-equivalent proportional counter.
AB  - The lineal-energy spectra for monoenergetic and quasi-monoenergetic neutrons of 8
      keV to 65 MeV were obtained using a tissue-equivalent proportional counter
      (TEPC). The frequency-mean lineal energy, the dose-average lineal energy and mean
      quality factor were estimated from the measured data. The neutron absorbed doses
      obtained with this TEPC were compared with the kerma coefticient for A-150
      plastic defined by ICRP 26 and the mean quality factors were compared with the
      data of ICRP 74. respectively. These comparisons indicated good agreement between
      them.

PMID- 12212903
TI  - Radiation protection for an ultra-high intensity laser.
AB  - Radiological characterisation of an experimental chamber and other areas of an
      ultra-high intensity laser facility (-terawatt) revealed significant levels of X
      ray, gamma and neutron radiation. Different techniques were used to detect and
      measure this radiation: TLD. photographic film, bubble detectors and germanium
      spectrometry. A test series of radiological measurements was made for 150 laser
      shots (300 femtoseconds) with energies in the 1 to 20 J range and a target
      illuminance of 10(19) W.cm2. Gamma dose equivalents in the vicinity of the
      chamber varied between 0.7 and 73 mSv. The dose equivalent due to the neutron
      component was evaluated to be 1% of the gamma dose equivalent. The amount of
      radiation generated depends on the laser energy and the nature of the target. No
      activation or contamination of the chamber or target holder were observed. Ultra
      high intensity lasers are being extensively developed at the present time and the
      investigations performed demonstrate that it is necessary to take radiological
      risks into consideration in the design of ultra-high intensity laser facilities
      and to define personnel access conditions.

PMID- 12212904
TI  - The CERN-EU high-energy reference field (CERF) facility for dosimetry at
      commercial flight altitudes and in space.
AB  - A reference facility for the calibration and intercomparison of active and
      passive detectors in broad neutron fields has been available at CERN since 1992.
      A positively charged hadron beam (a mixture of protons and pions) with momentum
      of 120 GeV/c hits a copper target, 50 cm thick and 7 cm in diameter. The
      secondary particles produced in the interaction traverse a shield, at 90 degrees
      with respect to the direction of the incoming beam. made of either 80 to 160 cm
      of concrete or 40 cm of iron. Behind the iron shield, the resulting neutron
      spectrum has a maximum at about 1 MeV, with an additional high-energy component.
      Behind the 80 cm concrete shield, the neutron spectrum has a second pronounced
      maximum at about 70 MeV and resembles the high-energy component of the radiation
      field created by cosmic rays at commercial flight altitudes. This paper describes
      the facility, reports on the latest neutron spectral measurements, gives an
      overview of the most important experiments performed by the various collaborating
      institutions over recent years and briefly addresses the possible application of
      the facility to measurements related to the space programme.

PMID- 12212905
TI  - Scattered doses to different parts of cancer patients during radiotherapy
      treatment in Nigeria.
AB  - The doses over various parts of the body of 7 patients with cancers of the
      pharynx, breast and cervix during radiotherapy treatment with a megavoltage 60Co
      therapy machine were measured using LiF TL dosemeters. The doses on the surface
      of the patients outside the primary beam were found to vary with a maximum of 366
      mGy at the abdomen of a cervix cancer patient to a minimum value of 1.1 mGy at
      the left arm and left leg of a pharynx cancer patient. The observed variations in
      the doses were attributed to the difference in patients' tumour location,
      exposure and anatomy. In the treatment of pregnant women and women of
      childbearing age, the results presented will be a good starting point for
      estimation of fetus doses and doses to organs outside the planning region.

PMID- 12212906
TI  - Identification of sources of high radon levels in Slovenian schools.
AB  - The sources of radon were investigated in twenty selected schools with high room
      levels of radiation. A combination of radon measuring techniques was applied:
      etched track and electret detectors to obtain average indoor air radon
      concentration. devices to record radon concentration continuously and thus
      characterise its diurnal variation, and alpha scintillation cells to analyse air
      from potential sources of radon entry. In some cases, a single strong source was
      identified (e.g. sinks, sub-floor channels), while in others the poor quality of
      the basic concrete slab was responsible for high indoor radon concentrations. The
      combination of etched track and electret detectors and alpha scintillation cells
      was essential for locating these sources.

PMID- 12212907
TI  - Dr. Ira Krull.

PMID- 12212908
TI  - Fluorescence labeling methods for microchannel plate capillary electrophoresis
      DNA sizing.
AB  - DNA analysis on microchannel plate (MCP) capillary electrophoresis platforms will
      be advanced by the development of new methods for the fluorescence labeling of
      analytes and standard sizing ladders. Here we evaluate end-labeling of
      commercially available DNA ladders and polymerase chain reaction (PCR) amplicons
      with terminal deoxynucleotidyl transferase (TdT) as a method for fluorescent
      double-stranded DNA sizing analysis. A PCR-based procedure for the facile
      construction of custom energy-transfer-labeled DNA sizing ladders is also
      presented. High-resolution sizing of single-stranded DNA fragments is
      demonstrated with this energy-transfer-labeled ladder. These DNA labeling
      procedures will be useful for double-and single-stranded DNA analyses on
      microdevices and other electrophoretic platforms.

PMID- 12212909
TI  - Genetic algorithms as a tool for capillary electrophoresis method development.
AB  - Capillary electrophoresis is a powerful and versatile analytical tool due to the
      wide range of separation variables and separation methods possible. CE permits
      the combination of multiple separation mechanisms (e.g., chiral modifiers,
      polarity, pH) for the analysis of a large variety of compounds. The main
      advantage of CE (i.e., the broad range of separation variables) has thus far
      limited its application. This is due to the nonlinear influence and interactions
      of different parameters on separation quality, making it difficult to predict
      trends for the optimization of separation systems and hence hindering CE method
      development. In this paper, we present a means for rationalizing method
      development for CE separations using a genetic algorithm. We provide selected
      examples of separation enhancements achieved in the field of nucleotide and
      nucleotide sugar separation. An improved method for the enantioselective
      separation of amino acid derivatives (2-acetylamino-3-phenyl-propionic acid) will
      also be presented.

PMID- 12212910
TI  - Capillary electrophoretic separation by double-strand polyaniline-coate
      capillaries of the advanced glycation endproducts formed from N-alpha-acetyl-L
      lysine with reducing sugars.
AB  - Capillary electrophoresis using a capillary coated with a double-strand coating
      of polyaniline:poly(methyacrylate-co-acrylic acid) (PAN:P[MA-AAI) was used to
      separate advanced glycation endproducts (AGEs) formed at 37 degrees C from model
      systems containing either glucose (Glc), fructose (Fru), or glyceraldehyde (GA)
      and N-alpha-acetyl-L-lysine (NALys). The presence of the P(MA-AA) as a second
      strand in the polymer allows the maintenance of the conductive state of the PAN
      at a wide pH range. Effects of buffer pH and coating concentration on the
      electroosmotic flow (EOF) were investigated. More AGE species can be detected for
      the GA/NALys mixtures using this coated capillary than upon an uncoated
      capillary. The coating procedure is simple and the stability of the coated
      capillary is good.

PMID- 12212911
TI  - Capillary electrophoresis determination of two reactive dyes: monitoring of
      activation and hydrolysis in different alkali media.
AB  - HPLC often meets with difficulty in analyzing reactive dyes, their activation,
      and posterior hydrolysis. In this work, capillary electrophoresis methodology for
      two reactive dyes, C.I. Reactive Black 5 and C.I. Reactive Red 198, was studied.
      The methods developed permit the separation and detection of these reactive dyes
      and their major hydrolytic products. These methods can be used successfully for
      the optimization of these dye syntheses, purification process, formulation, and
      also to monitor effluents and dye-bath mixtures and extrapolation to similar
      compounds. Simple background electrolyte systems, such as 10 mM phosphate or
      0.65% hydroxypropylmethylcellulose in 40 mM acetate, were used to follow the
      hydrolysis mechanism and process in the two different alkali media studied.

PMID- 12212912
TI  - Effect of sample preparation and pH-mediated sample stacking on the analysis of
      multiplexed short tandem repeats by capillary electrophoresis.
AB  - An amplification system was used in this study to evaluate the effect of sample
      preparation and its injection on the electrophoretic separation by capillary
      electrophoresis using a commercially available capillary electrophoresis
      instrument. The effect of dilution of amplified samples in water and in different
      sources of formamide (with conductivity values ranging from 47 to 1000 microS)
      was evaluated, as was contamination of the sample with high DNA concentrations or
      buffer salts. Although resolution remained constant in the different solvents
      tested, the sensitivity increased in samples diluted in water and high-purity
      formamide. An on-column sample preconcentration method for capillary-based DNA
      analysis was evaluated to increase the sensitivity of low-quality samples. This
      technique, pH-mediated sample stacking, is based on the injection of NaOH
      immediately before sample injection: A neutralization reaction occurs between OH-
      and tris+ ions so that a low-conductivity zone is created at the head of the
      capillary. DNA fragments are concentrated at the front of this zone. Using coated
      capillaries with hydroxycellulose 2% (MW 250,000) as a separation matrix, an
      improvement in sensitivity was detected in all the solvents studied. The gain in
      sensitivity was higher for more conductive solvents, and was not correlated with
      the size of the DNA fragments.

PMID- 12212913
TI  - Determination of cephalexin in oral suspensions by micellar electrokinetic
      chromatography.
AB  - A simple and efficient micellar capillary electrophoresis method for the analysis
      of cephalexin in oral suspensions is described. The analysis was carried out in a
      bare silica capillary with 75 microm i.d. and total length of 50 cm (28 cm to the
      detector) with a buffer solution containing 20 mM sodium tetraborate, 20 mM
      sodium dodecyl sulfate, and 0.1% laurylpolyoxiethylenic ether. The applied
      voltage was 15 kV. Detection was achieved by ultraviolet absorption at 210 nm.
      The calibration curve was linear within the concentration range from 40.0 to 120
      microg/mL with a correlation coefficient of 0.9998. The percentage recovery was
      found to be 100.09 +/- 0.56. The method showed good selectivity and resolution of
      the drug impurities, and was found suitable to study cephalexin stability in
      pharmaceutical preparations.

PMID- 12212914
TI  - Capillary electrophoresis as a method for determining the hydrolysis rate
      constant of raffinose.
AB  - Capillary electrophoresis was first employed for the determination of the
      hydrolysis rate constant of trisaccharide raffinose. Raffinose hydrolyzes in
      acidic medium at different temperatures; the hydrolysis products, including
      melibiose and fructose, were determined quantitatively. The concentration change
      in hydrolysis products over time provided useful information for calculating the
      hydrolysis constant of raffinose. The temperature dependence of the hydrolysis
      rate constant was used to calculate raffinose hydrolysis activation energy, which
      corresponds to the literature value.

PMID- 12212915
TI  - Brief report: prevalence of autism spectrum conditions in children aged 5-11
      years in Cambridgeshire, UK.
AB  - The study aimed to establish prevalence of the broader autistic spectrum,
      including Asperger syndrome, in 5- to 11-year-olds in Cambridgeshire, UK. Cases
      of diagnosed autism spectrum condition (ASC) in children who were in
      Cambridgeshire schools and aged between 5 and 11 years on 31 December 1999 were
      sought using public records, screening instruments, educational psychology and
      special educational needs coordinator (SENCO) records. We report a prevalence of
      ASC in the age group 5-11 years of almost 0.6 percent (57 in 10,000). This is 11
      times higher than the rate of classic autism but in line with other recent
      national and international rates for the broader spectrum. In the responding
      mainstream schools the prevalence was 0.33 percent. In the responding special
      school population it was 12.5 percent. The overall sex ratio of the children with
      ASC replicated findings for classical autism of 4:1 (M:F), but in those children
      being educated in mainstream schools the sex ratio was 8:1 (M:F).

PMID- 12212916
TI  - Early intervention system for preschool children with autism in the community:
      the DISCOVERY approach in Yokohama, Japan.
AB  - The article reports on DISCOVERY, a conceptual model for a clinical system of
      early detection and early intervention in cases of autism that has been
      implemented inYokohama, Japan. The minimal requirements for this system are
      subsystems dealing with detection, diagnosis and intervention. Specific issues
      involving early diagnosis that complicate the design of the system are the
      seemingly contradictory considerations of early versus precise diagnosis, the
      undifferentiated recognition of a child's disorder on the part of the parents,
      and the difficulty of establishing cooperative working relationships among
      related facilities. To overcome these issues, an 'interface' linking con secutive
      subsystems is emphasized in the DISCOVERY model. A clinical system based on this
      model has been developed in Yokohama. This system not only benefits clinical
      performance, but will also add significantly to research on autism.

PMID- 12212917
TI  - Challenging behaviour: a challenge to change.
AB  - People with intellectual disability often exhibit severe behavioural problems.
      Treatment of these problems is frequently very difficult. In The Netherlands,
      parents, institutes, schools and others can request the services of an
      independent advisory team with a pool of professionals who have experience with
      individuals who exhibit challenging behaviour. In this article the methods of the
      team will be described using a 24-year-old man as an example. The process took
      almost 7 years. Finally, this man, who had been living full time in one room in
      total isolation from the rest of the world, fulfilled his heart's desire-
      visiting the UK by Hovercraft.

PMID- 12212918
TI  - The effectiveness of parent management training to increase self-efficacy in
      parents of children with Asperger syndrome.
AB  - This study was a trial of an intervention programme aimed to improve parental
      self-efficacy in the management of problem behaviours associated with Asperger
      syndrome. The intervention was compared across two formats, a 1 day workshop and
      six individual sessions, and also with a non-intervention control group. The
      results indicated that, compared with the control group, parents in both
      intervention groups reported fewer problem behaviours and increased self-efficacy
      following the interventions, at both 4 weeks and 3 months follow-up. The results
      also showed a difference in self-efficacy between mothers and fathers, with
      mothers reporting a significantly greater increase in self-efficacy following
      intervention than fathers. There was no significant difference between the
      workshop format and the individual sessions.

PMID- 12212919
TI  - Temperament and character in adults with Asperger syndrome.
AB  - To study the personality characteristics of adults with Asperger syndrome, and
      investigate the value of self-rating personality inventories, we administered the
      Temperament and Character Inventory (TCI) to 31 outpatients with Asperger
      syndrome. The TCI is a self-rating personality inventory that has been validated
      in the Swedish general population. The results were compared with age- and sex
      matched norm groups. Participants with Asperger syndrome scored significantly
      higher on harm avoidance and lower on self-directedness and cooperativeness.
      Reward dependence and novelty seeking tended to be low. They also had
      significantly higher rarity scores, reflecting idiosyncratic perspectives. The
      most common temperament configurations were 'obsessional', 'passive-dependent'
      and'explosive'. Character, reflecting conceptual maturity, was poorly developed
      in the majority of our subjects. The self-ratings of persons with Asperger
      syndrome thus indicated anxious personalities with coping difficulties in the
      areas of social interaction and self-directedness, a picture corresponding to the
      clinical descriptions of Asperger syndrome.

PMID- 12212920
TI  - Beyond expectations: autism, understanding embarrassment, and the relationship
      with theory of mind.
AB  - The ability of high-functioning individuals with autism to understand the complex
      emotion of embarrassment, and how this relates to an understanding of theory of
      mind, was investigated. Scenarios involving embarrassing and non-embarrassing
      situations were presented to a group with autism and three comparison groups.
      Participants were required to rate the level of embarrassment felt by the
      protagonist and to justify their choices. The results indicated that those with
      autism generally gave similar ratings of embarrassment as the comparison groups,
      but did show significant difficulty with non-embarrassing scenarios, and in
      providing appropriate justifications for embarrassment. In addition, a
      significant relationship between scores from false belief tasks and justification
      scores was found, supporting the proposed link between theory of mind skills and
      understanding embarrassment. Participants with autism did, however, show a higher
      than expected understanding of this complex emotion.

PMID- 12212921
TI  - Urinary peptides in Rett syndrome.
AB  - Rett syndrome is a neuro-developmental disorder related to autistic behavior.
      Persons with autism have previously been found to have hyperpeptiduria. We here
      report a significantly higher level of peptides in the first fasting morning
      urine from 53 girls with Rett syndrome (both classical and congenital) compared
      with 53 healthy girls. This elevation in urinary peptides was similar to that in
      35 girls with infantile autism. As in persons with autism, the individual levels
      of urinary peptides in the Rett syndrome group varied, and about a fifth were
      within the normal range. Levels of peptides were lower in girls with classic Rett
      syndrome than in girls with congenital Rett syndrome. This may be due to
      different etiological causes or to active and stagnant phases of the disease.
      Urine from girls with Rett syndrome was found to have higher frequency and higher
      levels of some urinary peptides that may cause inhibition of brain maturation and
      epilepsy

PMID- 12212922
TI  - Selection of a T-cell line resistant to stavudine and zidovudine by prolonged
      treatment with stavudine.
AB  - It has been demonstrated that prolonged treatment with nucleoside analogues, such
      as 3'-azido-3'-deoxythymidine (zidovudine), 2',3'-dideoxycytidine (zalcitabine)
      and 9-(2-phosphonylmethoxyethyl) adenine (PMEA), may cause selection of cells
      that are resistant to their anti-HIV activity. A human T-lymphoblastoid cell line
      that is resistant to the antiviral and cytotoxic activity of 2',3'-didehydro-3'
      deoxythymidine (stavudine) has developed as a result of prolonged treatment.
      These cells, called CEMstavudine, are also less sensitive to zidovudine. The
      cellular/pharmacological resistance acquired by the CEMstavudine cells is
      relatively low and appears to correlate with a reduction in thymidine kinase (TK)
      activity, rather than with a decreased expression of TK mRNA.

PMID- 12212923
TI  - Adherence to antiretroviral therapy and outcomes in HIV-infected patients
      enrolled in an induction/maintenance randomized trial.
AB  - OBJECTIVE: To examine the effect of adherence to therapy on early virological
      response, later virological failure, and occurrence of adverse events in HIV
      infected patients. DESIGN: A randomized trial of 3-month induction period of
      zidovudine/lamivudine/indinavir followed by a maintenance phase of
      zidovudine/lamivudine/indinavir, zidovudine/lamivudine or zidovudine/indinavir.
      MAIN OUTCOMES: Adherence was assessed by pill count. In the induction phase,
      early virological response was defined as plasma HIV-RNA<500 copies/ml at month 2
      and in the maintenance phase, virological failure was defined as plasma HIV-RNA
      >500 copies/ml in two consecutive specimens. RESULTS: The median adherence rate
      was 97% in both induction (n=366) and maintenance phase (n=237). In the
      maintenance phase, pairwise comparisons showed a lower adherence rate in
      zidovudine/lamivudine/indinavir versus zidovudine/lamivudine (P=0.03), or versus
      zidovudine/indinavir (P=0.05). Only 13% of patients had an adherence over the
      maintenance phase of 80% or lower, while 40% of patients occasionally had an
      adherence rate of 80% or lower during this phase. Among the 362 patients with
      documented HIV-RNA at month 2, 86% had an early virological response. Adherence
      of 80% or greater was the only variable statistically predictive to early
      virological response (P<0.001), while baseline CD4, baseline HIV-RNA, and
      adherence of 95% or greater were not associated to virological response. In the
      maintenance phase, adherence, baseline HIV-RNA, HIV-RNA at month 3 and treatment
      groups were independently predictive to time to virological failure. Analysis by
      randomized groups indicated that difficulty in adherence (<80%) was predictive to
      time to failure (P<0.001) only in both indinavir-containing regimens. Occurrence
      of two or more severe adverse events (grade 3 and 4) was higher in patients with
      poor adherence although not statistically associated (P=0.12), while no
      association was found with minor adverse events. CONCLUSION: Adherence rate was
      globally lower in patients maintaining the original triple-drug therapy compared
      with those receiving less intensive regimens. Adherence rate was a time-dependent
      variable. Adherence to antiviral regimen of 80% or greater was predictive to
      early virological response, and adherence rate lower than 80% or 95% was
      predictive to virological failure, especially in indinavir-containing regimens.
      Occurrence of adverse events was not clearly associated to adherence.

PMID- 12212924
TI  - A genotypic drug resistance interpretation algorithm that significantly predicts
      therapy response in HIV-1-infected patients.
AB  - OBJECTIVES: The development of a genotypic drug resistance interpretation
      algorithm, and the evaluation of its power to predict therapy outcome. DESIGN: A
      rule-based algorithm was established by an individual expert and was based on
      published and in-house results, independently from the data of the patients used
      in this evaluation. The predictive value of the algorithm for virological
      outcomes was retrospectively evaluated using the baseline genotype observed in
      patients on highly active antiretroviral therapy, failing virologically and
      subsequently starting a salvage regimen. METHODS: The independent association
      between the susceptibility score (calculated according to the algorithm) and the
      virological response at 3 months, was analysed using multivariable logistic
      regression and multiple linear regression models. RESULTS: In two clinical
      centres 240 patients were studied. At 3 months 35% had a viral load of <500 RNA
      copies/ml. Using multivariable logistic regression, the odds ratio of achieving a
      viral load <500 RNA copies/ml at month 3 per unit increase of susceptibility
      score was 2.0 (95% CI 1.3-3.1; P=0.002) after adjusting for baseline viral load,
      genotype-driven salvage therapy, number of new drugs in the regimen, use of a new
      drug class in the regimen, nelfinavir-containing salvage therapy and history of
      prior viral load <500 RNA copies/ml. Using multiple linear regression, the
      susceptibility score showed a significant linear correlation with the log viral
      load change (slope=-0.27 log10 RNA copies/ml; 95% CI -0.11 to -0.43; P=0.001)
      after adjusting for history of prior viral load <500 RNA copies/ml, number of new
      drugs in the salvage therapy, use of a new drug class in the salvage therapy and
      baseline viral load. CONCLUSIONS: This algorithm proved to be a significant
      independent predictor of therapy response at 3 months in this cohort of HIV-1
      infected patients on salvage therapy. However, it should be subject to regular
      updates as is needed in this fast developing field.

PMID- 12212925
TI  - A rapid phenotypic assay for detecting multiple nucleoside analogue reverse
      transcriptase inhibitor-resistant HIV-1 in plasma.
AB  - Zidovudine and other nucleoside analogue reverse transcriptase inhibitors
      (NRTIs), like zalcitabine and didanosine used for treatment of individuals
      infected with HIV-1, can select for viruses with Q151M and other associated
      mutations (for example, A62V, S68G, V751, F77L, F116Y) in the reverse
      transcriptase (RT) enzyme. These mutations confer resistance to multiple
      nucleoside analogues, and thereby compromise the efficacy of this class of drugs.
      Presently available phenotypic assays for detection of multiple nucleoside
      analogue resistant (MNR) HIV-1 require testing for each NRTI individually. Here
      we report an enzymatic RT assay that uses resistance to zidovudine triphosphate
      (zidovudine-TP) as a diagnostic biochemical marker of MNR HIV-1. This assay
      exploits the different biochemical mechanisms for zidovudine-resistance conferred
      by either Q151 M or T215Y/F mutations and the inability of conventional RT assays
      to detect T215Y/F-associated zidovudine resistance. The assay detects RT activity
      directly in plasma by using Amp-RT, an ultra-sensitive PCR-based RT assay. We
      show that enzymatic resistance to zidovudine-TP is specific to MNR RT and is
      distinguishable from both wild-type (WT) and RT containing classical zidovudine
      resistant mutations (D67N, K70R, T215Y/F, K219Q). Compared to WT, MNR HIV-1 RT
      had 5- to 36-fold increases in the concentration of drug required to inhibit 50%
      (IC50) of RT activity, depending on the presence of Q151 M alone or with
      additional MNR mutations. A screening assay utilizing 1 microM zidovudine-TP was
      developed and validated on 14 reference isolates, 37 plasma specimens, and seven
      patient-derived viruses. Twenty-three specimens were found to have reduced
      susceptibility to zidovudine-TP, and all had Q151 M. In contrast, 21 specimens
      were sensitive to zidovudine-TP, of which 12 had WT genotypes, four had T215Y/F,
      and five had T69S-insertions along with T215Y/F mutations. This RT-based
      phenotypic assay provides a specific and rapid tool for the direct identification
      and monitoring of Q151M-associated MNR HIV-1 in plasma.

PMID- 12212926
TI  - Co-receptor usage and HIV-1 intra-clade C polymorphisms in the protease and
      reverse transcriptase genes of HIV-1 isolates from Ethiopia and Botswana.
AB  - Knowledge of baseline amino acid substitutions arising at certain critical
      positions in the HIV-1 non-clade-B protease (PR) and reverse transcriptase (RT)
      enzymes may yield important information with regard to anticipation of responses
      to antiretroviral treatment and development of drug resistance. We have compared
      RT and PR sequences within HIV-1 clade C strains isolated from 14 treatment-naive
      patients originating from Ethiopia and Botswana with those of PR and RT consensus
      subtype B RT and PR sequences. Variations in the frequency of natural
      polymorphisms were observed in clade C isolates at drug-resistance sites. Intra
      clade C divergence among mutations within PR was statistically significant while
      that within RT was not. Only a M361 substitution in PR was shared among almost
      all isolates from Ethiopia and Botswana. Analysis of the co-receptor usage of
      clade C isolates from Ethiopia and Botswana supports the known preferential usage
      of the CCR5 co-receptor by HIV-1 clade C strains. No Ethiopian or Botswanian
      isolates exclusively used the CXCR4 co-receptor, which is consistent with most
      data obtained with HIV-1 clade B isolates.

PMID- 12212927
TI  - Using live pathogens to treat infectious diseases: a historical perspective on
      the relationship between GB virus C and HIV.
AB  - Recent reports that co-infection with GB virus C (GBV-C) is associated with a
      reduced mortality in HIV-infected individuals, a slower progression to AIDS, and
      lower HIV viral loads, suggest a potential role of GBV-C as therapy for HIV
      infection. Although not known to cause any human disease, GBV-C was only recently
      discovered and prospective studies assessing long-term consequences of infection
      have not been completed. Our understanding of the host-viral interactions between
      humans and GBV-C is in its infancy. Further research into the intriguing
      relationship between GBV-C and HIV is needed before intentional inoculation of
      GBV-C into individuals infected with HIV should proceed. This essay explores the
      history of the once-popular treatment of paretic tertiary syphilis with the blood
      borne pathogen Plasmodium vivax, providing a historical perspective on the
      current state of affairs between GBV-C and HIV. A brief review of GBV-C biology
      and human infection is followed by a discussion of the current challenges facing
      the use of this organism to treat HIV.

PMID- 12212928
TI  - A randomized clinical trial comparing nelfinavir or nevirapine associated to
      zidovudine/lamivudine in HIV-infected naive patients (the Combine Study).
AB  - BACKGROUND: Non-nucleoside reverse transcriptase inhibitor-containing regimens
      may be a valid alternative to protease inhibitor-containing regimens for initial
      antiretroviral therapy, but to date few studies comparing these two strategies
      have been performed. OBJECTIVE: To evaluate the efficacy and safety of nelfinavir
      or nevirapine associated to zidovudine/lamivudine in HIV-infected naive patients.
      DESIGN: Randomized, open-label, multicentre trial. SETTING: Twelve centres in
      Spain (9) and Argentina (3). PATIENTS: One hundred and forty-two HIV-infected
      naive patients without AIDS. INTERVENTIONS: Patients received combivir
      (zidovudine 300 mg/lamivudine 150 mg, twice-daily) plus either nelfinavir (1250
      mg) twice-daily (zidovudine/lamivudine/nelfinavir, n=70) or nevirapine (200 mg)
      twice-daily (zidovudine/lamivudine/nevirapine, n=72), and were followed for 12
      months. The primary endpoint was the proportion of patients with a plasma HIV-1
      RNA (pVL) of less than 200 copies/ml by PCR at 12 months. pVL of less than 20
      copies/ml (PCR), changes in CD4 counts, clinical progression and adverse events
      were also evaluated. Efficacy was assessed using intent-to-treat (ITT)
      (missing=failure) and on-treatment analysis. RESULTS: At 12 months in the ITT
      analysis the proportion of patients with pVL below 200 copies/ml was 60% (95% CI
      48.5-71.5) in the zidovudine/lamivudine/nelfinavir arm and 75% (95% CI 65-85) in
      the zidovudine/lamivudine/nevirapine arm (P=0.06), and the proportion below 20
      copies/ml was 50% (95% CI 38.3-61.7) and 65% (95% CI 54.2-76.2), respectively
      (P=0.06). No differences were found when comparing the subgroup of patients with
      baseline pVL of more than 100,000 copies/ml. A gain of +173 and +162 CD4
      cells/mm3, respectively, was observed. Zidovudine/lamivudine/nelfinavir was
      discontinued in 21% of patients, and zidovudine/lamivudine/nevirapine in 25%, due
      to toxicity (P>0.2). CONCLUSIONS: Our results suggest that
      zidovudine/lamivudine/nevirapine is at least as effective as
      zidovudine/lamivudine/nelfinavir as first-line therapy for HIV disease.

PMID- 12212929
TI  - Residual cell-associated unspliced HIV-1 RNA in peripheral blood of patients on
      potent antiretroviral therapy represents intracellular transcripts.
AB  - Unspliced HIV-RNA (HIV-UsRNA) associated with peripheral blood mononuclear cells
      (PBMCs) persists in patients on potent antiretroviral therapy even in the absence
      of detectable plasma HIV-RNA. To further characterize such residual HIV-RNA, cell
      associated virion-encapsidated HIV and intracellular unspliced HIV-RNA were
      differentiated and monitored using a novel highly sensitive method. In addition,
      expression of HIV-mRNA encoding tat and rev was assessed. PBMCs of patients with
      unsuppressed plasma viraemia harboured an extracellular fraction of HIV-UsRNA,
      which correlated highly with intracellular HIV-RNA levels. Thus, extracellular
      PBMC-associated HIV-RNA may, to a significant extent, reflect nascent virions
      attached to productively infected cells. Upon treatment with potent
      antiretroviral therapy resulting in plasma viraemia <50 copies/ml, expression of
      cell-associated viral particles was hardly discernible in PBMCs but transcription
      of unspliced HIV-RNA persisted. Given the virtual absence of rev-mRNA,
      translation of residual HIV-UsRNA was probably precluded by retention of these
      transcripts in the nucleus. As shown by limiting dilution analysis, HIV-1
      infected cells with such a repressed viral transcription pattern were observed at
      high frequencies in PBMC from untreated patients.

PMID- 12212930
TI  - The impact of coming out on health and health care access: the experiences of
      gay, lesbian, bisexual and two-spirit people.
AB  - This paper documents the experiences of health care access among gay, lesbian,
      bisexual and Two-Spirit (glbt-s) people in Canada. In particular, it addresses
      the importance of coming out as glbt-s to the development of good health and
      appropriate care. The paper reflects upon the impact of hiding one's sexual
      orientation on glbt-s people's experience of and use of health care resources and
      the responsibility of health care institutions to address homophobia and create
      supportive environments in order to facilitate the coming out process in health
      care settings. The central role of health care policy makers with regard to the
      articulation of gay-positive policy and practice in health care institutions is
      highlighted.

PMID- 12212932
TI  - Attitudes and knowledge concerning alcohol abuse: curriculum implications.
AB  - This study presents data regarding social work practitioner experiences,
      attitudes and knowledge about alcoholism. A standardized instrument was used to
      survey BSWs and MSWs (N = 105) at three sites in Canada. Significant findings
      were: (a) these practitioners had low levels of knowledge about alcoholism as
      measured on the Alcohol Knowledge Scale (AKS), and (b) professional experiences,
      not personal ones, shaped their knowledge. The latter included whether they had
      participated in any post graduate coursework/continuing education or conducted
      research with this population. Implications are directed toward curriculum
      development for educators and practitioners working in this field.

PMID- 12212931
TI  - Managing the behavior of the medically insured in Germany: the acceptance of cost
      sharing and risk premiums by members of the statutory health insurance.
AB  - In the course of the conflicts over the reform of statutory health insurance in
      Germany complaints about moral hazard-behavior on the part of the insured were
      repeatedly raised and linked to the demand for expanding managerial incentives
      aimed at reducing the consumption of health care benefits (copayments). However,
      critics and supporters of managerial incentives mostly neglect the perceptions
      and dispositions of the insured. In contrast, the article examines how members of
      the statutory health insurance scheme assess managerial intervention, namely cost
      sharing and risk premiums.

PMID- 12212933
TI  - Initiating malaria control programs in the third world: directives for short- and
      long-term solutions.
AB  - Although malaria is a growing problem affecting several hundred million people
      each year, many malarial countries lack successful disease control programs.
      Worldwide malaria incidence rates are dramatically increasing, generating fear
      among many people who are witnessing malaria control initiatives fail. In this
      paper, we explore two options for malaria control in poor countries: (1) the
      production and distribution of a malaria vaccine and (2) the control of
      mosquitoes that harbor the malaria parasite. We first demonstrate that the
      development of a malaria vaccine is indeed likely, although it will take several
      years to produce because of both biological obstacles and insufficient research
      support. The distribution of such a vaccine, as suggested by some economists,
      will require that wealthy states promise a market to pharmaceutical companies who
      have traditionally failed to investigate diseases affecting the poorest of
      nations. But prior to the development of a malaria vaccine, we recommend the
      implementation of vector control pro- grams, such as those using Bti toxin, in
      regions with low vector capacity. Our analysis indicates that both endogenous
      programs in malarial regions and molecular approaches to parasite control will
      provide pragmatic solutions to the malaria problem. But the successful control of
      malaria will require sustained support from wealthy nations, without whom vaccine
      development and vector control programs will likely fail.

PMID- 12212934
TI  - Sexual harassment and its consequences: a study within Turkish hospitals.
AB  - Sexual harassment remains a universal factor that can affect nursing performance
      and worker productivity in any type of health care facility. There are few
      studies in this area that have been conducted in developing countries. To measure
      the occurrence of sexual harassment, a questionnaire was given to 353 nurses in
      two different hospitals yielding a response rate of 61%. Overall, the majority of
      the respondents (n = 157 out of 251) reported that they had been subjected to
      sexual harassment in the workplace, and the harassment experience was strong
      enough to affect worker productivity. In addition, many nurses reported the
      belief that sexual harassment remains a disturbing problem in this developing
      country that should not be ignored. Based on these findings, implications for
      policy and further study are suggested.

PMID- 12212935
TI  - An overview of the genetic basis of antibiotic resistance in bacteria and its
      implications for agriculture.

PMID- 12212936
TI  - Alternatives to the use of antibiotics as growth promoters for monogastric
      animals.
AB  - Recently, more and more is becoming known about the mode of action of antibiotics
      as growth promoters (AMGP), particularly in relation to the development of
      microbial resistance. Consequently, the use of these AMGP is already restricted
      or forbidden in many countries. Therefore, to compensate for the possible
      decrease in production, a lot of work is now being done to investigate possible
      alternatives. Suitable alternatives must be both proven and cost-effective, for
      the conditions and diets as used at the farm level.

PMID- 12212937
TI  - The issue of antibiotic use in the livestock industry: what have we learned?

PMID- 12212938
TI  - Production of recombinant ovine interferon tau using a Bombyx mori nuclear
      polyhedrosis baculovirus expression system.
AB  - Ovine interferon tau (oIFN-tau) is an embryonic protein of critical importance in
      the establishment of pregnancy in the sheep. We have produced recombinant (r)
      oIFN-tau using a baculovirus expression system and demonstrated the biological
      activity of the protein produced. Bombyx mori larvae were infected with B. mori
      nuclear polyhedrosis virus (BmNPV), modified by inserting a cDNA coding for oIFN
      tau downstream of the strong polyhedron promoter. Following infection, antiviral
      activity of the haemolymph rose to a maximum of 3.6 x 10(8) u/mL (equivalent to 3
      mg roIFN-tau/mL) by day 5, when haemolymph was collected and stored frozen.
      Control haemolymph, collected from uninfected insects at an equivalent time,
      contained no antiviral activity. The roIFN-tau was partially purified by gel
      filtration column chromatography and the presence of roIFN-tau confirmed by
      western blotting. The biological activity of the partially purified roIFN-tau was
      tested in ewes. Treatment with roIFN-tau caused a significant delay in luteolysis
      confirming biological potency. The results demonstrate that this system can be
      successfully used to produce large quantities of roIFN-tau.

PMID- 12212939
TI  - Cloning and sequencing of quail and pigeon prion genes.
AB  - Quail and pigeon PrP genes were cloned and sequenced. Like mammalian PrP genes,
      quail and pigeon genes are encoded by a single exon of a single copy gene in the
      genome. All of the structural features of mammalian PrP genes were found in the
      quail and pigeon PrP gene. Compared with the nucleotide sequences of mammalian
      PrP, they display generally 30% similarity. When compared with chicken PrP's DNA
      sequence, they show a higher homology (90%), and an even higher homology (99%)
      when compared to each other. A phylogenetic tree was constructed to trace the
      evolution of the prion gene in animals.

PMID- 12212940
TI  - A 3800 gene microarray for cattle functional genomics: comparison of gene
      expression in spleen, placenta, and brain.
AB  - A cDNA microarray representing approximately 3800 cattle genes was created for
      functional genomic studies. The array elements were selected from > 7000 cDNA
      clones identified in a large-scale expressed sequence tag (EST) project that
      utilized spleen and normalized and subtracted placenta cDNA libraries. Sequence
      similarity searches of the 3820 ESTs represented on the array using BLASTN
      identified 3290 (86.1%) as putative human orthologs, with the remainder
      consisting of "novel" genes or highly divergent orthologs. Experiments were
      conducted with a prototype 768 gene microarray created from spleen cDNAs and with
      the 3800 gene array that included genes from spleen and placenta. The 768 gene
      array was used to profile RNA transcripts expressed by adult and fetal spleen.
      The 3800 gene array was used to profile transcripts expressed by adult brain and
      placenta. Microarray analysis of RNA extracted from fetal and adult spleen
      identified 29 genes that were differentially expressed two-fold or more.
      Transcriptional differences of two of these genes, IGJ and CTSS, were confirmed
      using TaqMan technology. The comparison of brain and placenta revealed 400 genes
      expressed at higher levels in brain and 72 genes expressed at higher levels in
      placenta. These results demonstrate the potential power of microarrays for
      understanding the molecular mechanisms of cattle development, disease resistance,
      nutrition, fertility and production traits.

PMID- 12212941
TI  - Identification of three SNPs in the porcine myostatin gene (MSTN).
AB  - Thirteen pairs of primers were designed for the entire porcine MSTN gene to
      enable PCR amplification for the detection of single nucleotide polymorphisms
      (SNPs) by a PCR-SSCP approach. Altogether 96.5% (1089/1128) of the encoding
      regions and 971 bp of the non-coding regions were screened. A total of three
      polymorphisms were identified with PCR-SSCP. They were located in the promoter,
      intron one and exon three regions of the gene. These polymorphisms were then
      confirmed to be point mutations (T --> A transversion, G --> A transition and C -
      > T transition respectively) by sequencing. Allele frequencies were determined
      for all three SNPs in several different pig breed populations. The polymorphisms
      were found to be rare in Western breeds, but much more common in Chinese breeds.
      Whether they have any relationship with the marked difference in lean meat mass
      between Western and Chinese breeds requires further study.

PMID- 12212942
TI  - Antibiotics as growth promotants: mode of action.
AB  - Recent concerns about the use of growth-promoting antibiotics in pig diets have
      renewed interest in the immunologic and growth-regulating functions of the
      gastrointestinal (GI) tract. The numerically dense and metabolically active
      microbiota ofthe pig GI tract represents a key focal point for such questions.
      The intestinal microbiota is viewed typically as a beneficial entity for the
      host. Intestinal bacteria provide both nutritional and defensive functions for
      their host. However, the host animal invests substantially in defensive efforts
      to first sequester gut microbes away from the epithelial surface, and second to
      quickly mount immune responses against those organisms that breach epithelial
      defenses. The impact of host responses to gut bacteria and their metabolic
      activities require special consideration when viewed in the context of pig
      production in which efficiency of animal growth is a primary objective. Here, we
      summarize the working hypothesis that antibiotics improve the efficiency of
      animal growth via their inhibition of the normal microbiota, leading to increased
      nutrient utilization and a reduction in the maintenance costs ofthe GI system. In
      addition, novel molecular ecology techniques are described that can serve as
      tools to uncover the relationship between intestinal microbiology and growth
      efficiency.

PMID- 12212943
TI  - Programs for monitoring antimicrobial resistance.

PMID- 12212944
TI  - Molecular ecological studies on spread of antibiotic resistance genes.

PMID- 12212945
TI  - Why and how antibiotics are used in swine production.
AB  - In summary, published research data clearly show that the use of antibiotics
      during all phases of growth benefits the rate and efficiency of body weight gain,
      reduces mortality and morbidity, reduces subclinical disease, and improves health
      in pigs. Also, antibiotics at breeding and during lactation benefits reproductive
      and lactational performance in sows. The economic benefits are several-fold
      greater than the cost of the antibiotic when a cost-effective antibiotic is used
      for this purpose. Monitoring and surveillance of microbial resistance in animals
      and humans has continued, with no animal-to-human infection path being clearly
      delineated. Although the incidence of antibiotic resistance in the human
      population remains high, there is no clear evidence that the levels or patterns
      have changed. The high levels of antimicrobial resistance in humans likely result
      from antibiotics prescribed directly to humans, because well over half of the
      antibiotics produced in the United States is used in human medicine. Whether
      antibiotic usage in swine, poultry, and other food-producing animals contributes
      to antibiotic resistance in the human population will continue to be debated.
      Even though antibiotics have been fed for nearly 50 years to literally billions
      of animals, there is still no convincing evidence of unfavorable health effects
      in humans that can be directly linked to the feeding of subtherapeutic levels of
      antibiotics to swine or other animals. Hopefully, policy decisions in the future
      regarding the use of antimicrobials in animals will be based on science and sound
      risk assessment, and not on emotionalism.

PMID- 12212946
TI  - The food safety perspective of antibiotic resistance.
AB  - Bacterial antimicrobial resistance in both the medical and agricultural fields
      has become a serious problem worldwide. Antibiotic resistant strains of bacteria
      are an increasing threat to animal and human health, with resistance mechanisms
      having been identified and described for all known antimicrobials currently
      available for clinical use. There is currently increased public and scientific
      interest regarding the administration of therapeutic and sub-therapeutic
      antimicrobials to animals, due primarily to the emergence and dissemination of
      multiple antibiotic resistant zoonotic bacterial pathogens. This issue has been
      the subject of heated debates for many years, however, there is still no complete
      consensus on the significance of antimicrobial use in animals, or resistance in
      bacterial isolates from animals, on the development and dissemination of
      antibiotic resistance among human bacterial pathogens. In fact, the debate
      regarding antimicrobial use in animals and subsequent human health implications
      has been going on for over 30 years, beginning with the release of the Swann
      report in the United Kingdom. The latest report released by the National Research
      Council (1998) confirmed that there were substantial information gaps that
      contribute to the difficulty of assessing potential detrimental effects of
      antimicrobials in food animals on human health. Regardless of the controversy,
      bacterial pathogens of animal and human origin are becoming increasingly
      resistant to most frontline antimicrobials, including expanded-spectrum
      cephalosporins, aminoglycosides, and even fluoroquinolones. The lion's share of
      these antimicrobial resistant phenotypes is gained from extra-chromosomal genes
      that may impart resistance to an entire antimicrobial class. In recent years, a
      number of these resistance genes have been associated with large, transferable,
      extra-chromosomal DNA elements, called plasmids, on which may be other DNA mobile
      elements, such as transposons and integrons. These DNA mobile elements have been
      shown to transmit genetic determinants for several different antimicrobial
      resistance mechanisms and may account for the rapid dissemination of resistance
      genes among different bacteria. The increasing incidence of antimicrobial
      resistant bacterial pathogens has severe implications for the future treatment
      and prevention of infectious diseases in both animals and humans. Although much
      scientific information is available on this subject, many aspects of the
      development of antimicrobial resistance still remain uncertain. The emergence and
      dissemination of bacterial antimicrobial resistance is the result of numerous
      complex interactions among antimicrobials, microorganisms, and the surrounding
      environments. Although research has linked the use of antibiotics in agriculture
      to the emergence of antibiotic-resistant foodborne pathogens, debate still
      continues whether this role is significant enough to merit further regulation or
      restriction.

PMID- 12212947
TI  - Experience of feeding pigs without antibiotics: a European perspective.

PMID- 12212948
TI  - Alternatives to antibiotic use: probiotics for the gut.

PMID- 12212949
TI  - Transbronchial biopsy as a tool to evaluate small-airways disease in asthma.
      Pros.

PMID- 12212950
TI  - Transbronchial biopsy as a tool to evaluate small-airways disease in asthma.
      Cons.

PMID- 12212951
TI  - Hypoxia, nitrogen balance and body weight.

PMID- 12212952
TI  - Transbronchial biopsy as a tool to evaluate small airways in asthma.
AB  - Small airway (SA) inflammation in asthmatics is poorly understood. Surgical
      biopsies to obtain peripheral lung tissue are seldom justified in asthmatics.
      Therefore, the authors hypothesised that transbronchial biopsy could be an
      alternative approach to evaluate SA in asthma. Transbronchial and endobronchial
      biopsy tissue samples (TBBX and EBBX) from 12 severe asthmatics were evaluated
      for airway and parenchymal total inflammatory cell count expressed as the sum of
      immunostained T-cells (CD3), macrophages (CD68), mast cells (tryptase AAI),
      neutrophils (neutrophil elastase) and eosinophils (EG2) per mm2. The large
      airways (LA) were evaluated in EBBXs, while SA, medium airways (MA) and alveolar
      tissue (AT) were evaluated in TBBXs. When cell counts from SA, MA, LA and AT were
      compared, SA had a significantly higher cell count than MA or LA (SA 1011 x mm(
      2) (539-1,290), MA 346 x mm(-2) (223-415), LA 332 x mm(-2) (189-416), AT 464 x
      mm(-2) (298-834)). The cell density and pattern of the inflammatory cell
      distribution in subjects with TBBXs appeared similar to those in three severe
      asthmatics whose inflammatory cells were analysed in surgical tissue samples.
      This study suggests that small airway may be identified and analysed in
      transbronchial biopsy tissue samples and therefore transbronchial biopsy tissue
      samples could expand the analysis of inflammation and tissue remodelling in
      asthma.

PMID- 12212953
TI  - Persistent asthma: disease control, resource utilisation and direct costs.
AB  - Despite evidence that adverse outcomes are less frequent when asthma management
      is optimised, the link between the level of control, disease severity and medical
      resource utilisation (MRU) is poorly documented. This relationship was
      investigated in a group of patients suffering from persistent asthma (Global
      Initiative for Asthma (GINA) > or = 2) in France. In 1998 a computerised family
      practice database was used to identify asthma patients aged 17-50 yrs.
      Information from the database was complemented by a patient survey to
      retrospectively assess the level of asthma control and hospital contacts. Costs
      of MRU over a 12-month study period were related to demographics, medical
      history, asthma control, and doses of inhaled corticosteroids prescribed during
      the prestudy period. A review of the computerised medical database identified
      1,038 adult patients with persistent asthma, who completed the survey
      questionnaire. Over a 12-month period, the mean cost of MRU was 549.8 euros for
      well-controlled patients, 746.3 euros per patient with moderate control, and
      1,451.3 euros per patient with poor control. Costs also increased significantly
      with age, access to free asthma care, comorbid conditions, asthma symptoms in the
      past year and whether inhaled corticosteroids had been prescribed before the
      study period. In patients with persistent asthma, large differences were observed
      in the use of medical resources according to control and severity. Therefore, if
      patients appropriately use prescribed control therapy, their use of medical
      resources may be reduced.

PMID- 12212954
TI  - Tachykinins and airway microvascular leakage induced by HCl intra-oesophageal
      instillation.
AB  - Gastro-oesophageal reflux is a common clinical disorder associated with a variety
      of respiratory symptoms, including chronic cough and exacerbation of asthma. In
      this study, the potential role of acid-induced tachykinin release was examined in
      guinea pigs and rabbits, by examining the effects of the tachykinin NK1 and NK3
      receptors antagonists (SR 140333 and SR 142801, respectively) (1-10 mg x kg(-1))
      on plasma protein extravasation induced in airways by hydrochloric acid (HCl)
      infusion in the oesophagus. Guinea pigs were anaesthetised with urethane, while
      rabbits were subject to neuroleptoanalgesia with hypnorm. Airway vascular leakage
      was evaluated by measuring extravasation of Evans blue dye. All animals were
      pretreated with atropine (1 mg x kg(-1) i.p.), propranolol (1 mg x kg(-1) i.p.),
      phosphoramidon (2.5 mg x kg(-1) i.v.) and saline or tachykinin receptor
      antagonists (1-10 mg x kg(-1) i.p.). Infusion of 1 N HCl into the oesophagus led
      to a three- and five-fold increase in plasma extravasation in the main bronchi
      and trachea, respectively. This increase was largely prevented by the tachykinin
      NK1 and NK3 receptor antagonists SR 140333 and SR 142801 (1-10 mg x kg(-1)).
      These results suggest that protein extravasation in the airways, as induced by
      intraoesophageal HCl infusion, is mainly dependent on the release of tachykinins,
      and that both NK1 and NK3 tachykinin receptors are involved. The results suggest
      that HCl-induced sensory nerve stimulation may act in the periphery on
      intermediate neurons and/or ganglia where NK3 receptors have been shown to play
      an important role.

PMID- 12212955
TI  - Rhinovirus infection in nonasthmatic subjects: effects on intrapulmonary airways.
AB  - The common cold is a highly prevalent, uncomplicated upper airway disease.
      However, rhinovirus (RV) infection can lead to exacerbation of asthma, with
      worsening in airway hyperresponsiveness and bronchial inflammation. The current
      authors questioned whether such involvement of the intrapulmonary airways is
      disease specific. Twelve nonatopic, healthy subjects (forced expiratory volume in
      one second (FEV1) >80% predicted, provocation concentration causing a 20% fall in
      FEV1 (PC20) >8 mg x mL(-1)) were experimentally infected with RV16. Next to PC20
      and the maximal response to methacholine (MFEV1 and MV'40p), the numbers of
      mucosal inflammatory cells and epithelial intercellular adhesion molecule (ICAM)
      1 expression in bronchial biopsies were assessed before and 6 days after RV16
      inoculation. RV16 infection induced a small but consistent increase in maximal
      airway narrowing, without a change in PC20. There was a significant increase in
      bronchial epithelial ICAM-1 expression after RV16, whereas inflammatory cell
      counts did not change. Nevertheless, the change in the number of submucosal CD3+
      cells was correlated with the change in MV'40p. In conclusion, rhinovirus
      infection in normal subjects induces a limited, but significant increase in
      maximal airway narrowing, which is associated with changes in bronchial T-cell
      numbers. Together with the upregulation of bronchial epithelial intercellular
      adhesion molecule-1, these findings indicate that, even in healthy subjects,
      rhinovirus infection affects the intrapulmonary airways.

PMID- 12212956
TI  - Repeated allergen exposure changes collagen composition in airways of sensitised
      Brown Norway rats.
AB  - Increased or altered collagen deposition in the airway wall is one of the
      characteristics of airway remodelling in asthma. The mechanisms underlying this
      increase, and its functional consequences remain to be established further.
      Representative in vivo animal models might be useful in this respect. In the
      present study, collagen deposition after prolonged allergen exposure was
      characterised in the airway wall of Brown Norway rats. Sensitised rats were
      repeatedly exposed to ovalbumin (OA) or phosphate-buffered saline during 2 and 12
      weeks. The deposition of collagen type I, III, IV, V and VI was not altered in
      animals exposed to OA for 2 weeks. After 12 weeks of OA exposure, more collagen
      type I was deposited in the inner and outer airway wall and more type V and VI
      collagen was observed in the outer airway wall. At 12 weeks the number of
      vessels, identified via type IV collagen staining was not increased, but the
      total vessel area was. In conclusion, prolonged allergen exposure in sensitised
      rats is associated with enhanced deposition of type I, V and VI collagens and
      increased vascularity. This suggests that some aspects of airway remodelling in
      asthma could be driven by long-term allergen exposure.

PMID- 12212957
TI  - Relaxation of proximal and distal isolated human bronchi by halothane, isoflurane
      and desflurane.
AB  - Volatile anaesthetics relax airway smooth muscle in vitro. The amount of
      relaxation might depend on the type and concentration of volatile anaesthetics,
      the calibre and precontraction level of the bronchi, and also on the species
      considered. These effects were investigated on isolated human bronchi. Isometric
      relaxations produced by halothane, isoflurane and desflurane bubbled on human
      bronchial rings precontracted with carbachol were recorded and compared with time
      controls. Volatile anaesthetics induced a concentration-dependent relaxation at
      0.66, 1.33 and 2 minimum alveolar concentration (MAC). The relaxation was greater
      in mildly (carbachol 3x10(-7) M) than in highly (carbachol 2x10(-6) M)
      precontracted bronchi. Halothane was more potent in relaxing distal as compared
      to proximal bronchi; this differential effect was less pronounced with isoflurane
      and not observed with desflurane. While the three volatile anaesthetics induced
      similar relaxation on proximal bronchi, halothane was significantly more potent
      than desflurane on distal bronchi, with isoflurane being intermediate. The
      relaxation induced by 1.33 MAC of halothane, isoflurane and desflurane on
      moderately precontracted distal bronchi (carbachol 1x10(-6) M) was attenuated by
      pretreatment with glibenclamide 1x10(-5) M. In conclusion, halothane, isoflurane
      and desflurane exert direct but differential relaxant effects on human isolated
      bronchial smooth muscle. This may provide supplemental bronchodilation during
      anaesthesia. Although adenosine triphosphate-sensitive K+ channels are involved
      in these relaxant effects, they are unlikely to explain the observed differences
      between the three volatile anaesthetics.

PMID- 12212958
TI  - Effects of insulin-like growth factor on nitrogen balance during hypoxic
      exposure.
AB  - Acute exacerbations of chronic obstructive pulmonary disease (COPD) accompanied
      with hypoxaemia may induce net protein catabolism and hypoxaemia could be an
      important trigger of a systemic catabolic response. The aim of this study was to
      examine the anabolic effects of recombinant human insulin-like growth factor-I
      (IGF-1) in rats exposed to hypoxia. Although acute hypoxia is usually accompanied
      with a decrease in dietary intake, the usual nitrogen intake was maintained in
      this study. Sprague-Dawley rats were maintained by continuous infusion of
      solution for total parenteral nutrition for 6 days. The animals were then
      randomly assigned to a normoxic (N) or a hypoxic (H) group. During the last 3
      days of the experiment N and H rats were randomised to receive either IGF-I or
      vehicle. Exposure to hypoxia caused a decrease in body-weight gain accompanied by
      a negative nitrogen balance, which was mainly due to increased urinary nitrogen
      excretion. No effect of recombinant human IGF-I treatment on body weight was
      observed during exposure to hypoxia, although nitrogen balance normalised. The co
      infusion of recombinant human insulin-like growth factor-1 and total parenteral
      nutrition has a significant net anabolic effect, as demonstrated by nitrogen
      retention and reduction in urine protein excretion observed in rats. Insulin-like
      growth factor-1 may help to ameliorate the protein catabolism observed under
      hypoxic conditions.

PMID- 12212959
TI  - Effect of hypobaric hypoxia on blood gases in patients with restrictive lung
      disease.
AB  - Several publications have reported effects of hypobaric conditions in patients
      with chronic obstructive pulmonary disease. To the current authors' knowledge,
      similar studies concerning patients with restrictive lung disease have not been
      published. The effect of simulated air travel in a hypobaric chamber on arterial
      blood gases, blood pressure, and cardiac frequency during rest and 20 W exercise,
      and the response to supplementary oxygen in 17 patients with chronic restrictive
      ventilatory impairment has been investigated. Resting oxygen tension in arterial
      blood (Pa,O2) decreased from 10.4+/-1.6 kPa at sea level to 6.5+/-1.1 kPa at
      2,438 m simulated altitude, and decreased further during light exercise in all
      patients (5.1+/-0.9 kPa). Pa,O2 at this altitude correlated positively with sea
      level Pa,O2 and transfer factor of the lung for carbon monoxide (TL,CO), and
      negatively with carbon dioxide tension in arterial blood (Pa,CO2). Pa,O2
      increased to acceptable levels with an O2 supply of 2 L x min(-1) at rest and 4 L
      x min(-1) during 20 W exercise. In conclusion, most of the patients with
      restrictive ventilatory impairment developed hypoxaemia below the recommended
      levels of in-flight oxygen tension in arterial blood during simulated air travel.
      Light exercise aggravated the hypoxaemia. Acceptable levels of oxygen tension in
      arterial blood, with only a minor increase in carbon dioxide tension in arterial
      blood, were obtained by supplementary oxygen.

PMID- 12212960
TI  - Ambulatory oxygen improves quality of life of COPD patients: a randomised
      controlled study.
AB  - It is unknown whether acute response to ambulatory oxygen (O2) predicts longer
      term improvement in health-related quality of life (HRQL) in chronic obstructive
      pulmonary disease (COPD) patients. The aims of this study were 1) to assess the
      short-term clinical impact, as determined by HRQL, of ambulatory O2 in a 12-week,
      double-blind, randomised crossover study of O2 (versus cylinder compressed air)
      of dyspnoeic but not chronically hypoxic COPD patients with exertional
      desaturation < or = 88% (n=41), and 2) to determine whether either baseline
      characteristics or acute response to O2 predicts short-term (12 weeks) response.
      Primary outcome measures were Chronic Respiratory Questionnaire (CRQ), Hospital
      Anxiety and Depression scale and the short form (SF)-36. Improvements were seen
      in all domains of the CRQ for cylinder O2 compared with cylinder air. Significant
      improvements were also noted in anxiety and depression and in certain domains of
      the SF-36. There were 28 (68%) acute responders to cylinder O2 (defined as
      increase in 6-min walk > or = 54 m or decrease in post-Borg dyspnoea > or = 1)
      and 23 (56%) short-term responders (defined as clinically significant improvement
      in CRQ). However, acute and short-term responses were not correlated with no
      predictors of short-term response identified. At study completion, 14 (41%) of
      acute or short-term responders did not want to continue therapy, with 11 citing
      poor acceptability or tolerability. Short-term ambulatory oxygen is associated
      with significant improvements in health-related quality of life. These benefits
      cannot be predicted by baseline characteristics or acute response. Despite acute
      or short-term response, a substantial proportion of patients declined ambulatory
      oxygen.

PMID- 12212961
TI  - The association between diet and chronic obstructive pulmonary disease in
      subjects selected from general practice.
AB  - It is unclear why some smokers develop chronic obstructive pulmonary disease
      (COPD) whilst the majority do not. Antioxidants found in food may protect against
      lung tissue injury, but previous epidemiological studies are inconsistent and do
      not focus on those most at risk of COPD, namely smokers. This case-controlled
      study measured the difference in dietary intake between smokers and exsmokers
      with and without COPD. Cases were patients > 45 yrs of age with > 10 pack-yrs of
      smoking, a forced expiratory volume in one second (FEV1)/forced vital capacity
      (FVC) of < or = 70% and a FEV1 of < or = 80% of predicted. Controls were patients
      >45 yrs of age with > 10 pack-yrs of smoking, a FEV1/FVC of > 70% and a FEV1 >
      80% pred. Data were collected using validated questionnaires. Logistic regression
      analysis for an unmatched case-controlled study was performed. After controlling
      for other independent predictors of COPD, those with vegetable intake of > or = 1
      portion x day(-1) (93 g) were less likely to have COPD, as were those consuming >
      or = 1.5 portions x day(-1) of fruit. This was not due to an overall reduction in
      food/calorie intake caused by the disease because: 1) adjusting for body mass
      index did not alter the estimates; 2) the effect was specific to fruit and
      vegetables, i.e. not other food groups; and 3) the estimates from incident cases
      were similar. In conclusion, fruit and vegetable consumption is inversely
      associated with chronic obstructive pulmonary disease and may explain why some
      smokers do not develop chronic obstructive pulmonary disease.

PMID- 12212962
TI  - Screening for alpha1-Pi deficiency in patients with lung diseases.
AB  - In patients with pulmonary emphysema, studies have reported 2-3% of individuals
      with severe alpha1-Pi deficiency. The aims of this study were to evaluate the
      accuracy of a new method for quantifying alpha1-Pi through phenotyping from dried
      blood spots (DBS) and to test the hypothesis that the screening of a population
      at risk increases the detection rate for severe alpha1-Pi deficiency. The
      accuracy of phenotyping results from DBS was compared to conventional methods in
      a total of 555 individuals. In a prospective study 1,060 patients with chronic
      lung disease were screened for alpha1-Pi deficiency using DBS. The validation of
      the phenotyping method from DBS showed an accuracy of 100%. Out of 1,060 tested
      patients, none had a severe PiZ deficiency and only 3 had PiSZ, whilst 36 (3.34%)
      individuals were identified as heterozygous for PiMS and 39 (3.68%) for PiMZ. No
      patients with severe alpha1-Pi deficiency could be detected in this population
      and the frequency of PiMS or PiMZ detected was similar to that of the normal
      population. Thus, the screening of an unselected population of chronic
      obstructive pulmonary disease and asthma patients may not detect a large number
      of individuals with severe alpha1-Pi deficiency.

PMID- 12212963
TI  - Evidence of mast-cell activation in a subset of patients with eosinophilic
      chronic obstructive pulmonary disease.
AB  - Although asthma has been viewed mainly as an eosinophilic disease, and chronic
      obstructive pulmonary disease (COPD) as a neutrophilic disease, recent studies
      have shown increased neutrophil counts in severe asthma and sputum eosinophilia
      in some COPD patients. In an attempt to further characterise these two syndromes
      according to pathology, the current authors have conducted a study of induced
      sputum in 15 subjects with COPD, 17 asthmatics, and 17 nonatopic healthy
      individuals. Sputum was analysed for cytology and levels of eosinophil cationic
      protein (ECP), albumin, tryptase and soluble intercellular adhesion molecule-1.
      The COPD subjects differed from the asthmatics as they had higher sputum
      neutrophil and lower columnar epithelial cell counts, but there were no
      differences in any soluble marker studied. When compared to control subjects,
      both the asthmatic and COPD subjects had raised eosinophil counts and ECP levels.
      In a subset of COPD subjects with sputum eosinophilia (>3% of total cells),
      significantly increased levels of tryptase were detected. In conclusion, although
      chronic obstructive pulmonary disease is a more neutrophilic disease than asthma,
      the two diseases are difficult to distinguish on the basis of sputum levels of
      the soluble markers traditionally associated with asthma. However, a subset of
      patients with chronic obstructive pulmonary disease with airway eosinophilia and
      mast-cell activation might represent a distinct pathological phenotype.

PMID- 12212964
TI  - Response to hypoxia of pulmonary arteries in chronic obstructive pulmonary
      disease: an in vitro study.
AB  - Patients with chronic obstructive pulmonary disease (COPD) show impaired hypoxic
      pulmonary vasoconstriction that might contribute to abnormal gas exchange and
      could be related to endothelial dysfunction in pulmonary arteries. The aim of the
      study was to investigate the response of PA to hypoxic stimulus in vitro in COPD,
      and the role of endothelium-derived nitric oxide (NO) in this response. The
      pulmonary arteries of 25 patients who underwent lung resection were studied.
      Patients were divided into controls, COPD+normoxaemia (COPDN) and COPD+
      hypoxaemia (COPDH). Hypoxic vasoconstriction (HV) was evaluated before and after
      stimulation or inhibition of the endothelial release of NO, and in the presence
      of exogenous NO. Compared with the other groups, HV was reduced in COPDH. The
      magnitude of HV correlated with the oxygen tension in arterial blood. The hypoxic
      stimulus induced greater contraction after stimulating endothelial release of NO,
      whereas its inhibition practically abolished HV. Exogenous NO completely
      inhibited HV. Maximal relaxation induced by endothelium-dependent vasodilators
      correlated with the magnitude of HV. In conclusion, pulmonary arteries of
      patients with chronic obstructive pulmonary disease and hypoxaemia have an
      impaired response to hypoxic stimulus, and the endothelial release of nitric
      oxide modulates hypoxic vasoconstriction. The depressed response of pulmonary
      arteries to hypoxia may contribute to abnormal gas exchange in chronic
      obstructive pulmonary disease.

PMID- 12212965
TI  - Intravenous iloprost for treatment failure of aerosolised iloprost in pulmonary
      arterial hypertension.
AB  - Treatment with aerosolised iloprost, a prostacyclin analogue, has beneficial
      effects in patients with pulmonary arterial hypertension (PAH). It is unclear if
      patients, whose clinical condition deteriorates under treatment with aerosolised
      iloprost, benefit from switching to continuous intravenous iloprost. The current
      authors report on 16 patients with severe PAH who received continuous intravenous
      iloprost after primary or secondary failure of treatment with aerosolised
      iloprost. Determinants of efficacy were survival, New York Heart Association
      (NYHA) class, and walking distance in the 6-min walk test. Of 93 patients with
      PAH treated with aerosolised iloprost, 16 required switching to intravenous
      iloprost for clinical deterioration. These patients had severe right heart
      failure with a cardiac index of 1.6+/-0.2 L x min(-1) x m(-2) and a mixed-venous
      oxygen saturation of 52+/-6%. Five of these patients showed no improvement and
      eventually died. Three patients had further deterioration in NYHA class and
      exercise capacity; two of them underwent lung transplantation; the third patient
      is still alive. Eight patients showed marked clinical improvement; one underwent
      lung transplantation and the others are currently alive and stable. In the latter
      group of patients, the walking distance in the 6-min walk test increased from
      205+/-94 to 329+/-59 m. It was not possible to identify clinical or haemodynamic
      factors that would predict whether switching from inhaled to intravenous iloprost
      would have a beneficial effect. In patients with pulmonary arterial hypertension
      who deteriorated while being treated with aerosolised iloprost, switching to
      continuous intravenous iloprost caused substantial improvement in exercise
      capacity in eight of 16 patients but could not prevent progression of pulmonary
      hypertension in the remaining eight patients. Since it was impossible to predict
      the individual effects of this approach, intravenous prostaglandin treatment
      should be considered in pulmonary arterial hypertension patients who deteriorate
      while receiving iloprost aerosol.

PMID- 12212966
TI  - Adverse pulmonary vascular effects of high dose tricyclic antidepressants: acute
      and chronic animal studies.
AB  - Overdose of tricyclic antidepressants, which inhibit cellular serotonin (5-HT)
      uptake, sometimes causes acute respiratory syndrome-like symptoms. Their acute
      and chronic cardiopulmonary actions, which might be implicated, utilising both in
      vivo and ex vivo animal studies, were investigated in this study. Acute
      amitriptyline (AMI), iprindole and imipramine caused dose-dependent prolonged
      rises in pulmonary artery pressure and oedema in anaesthetised cats in vivo.
      Acute AMI, in isolated ex vivo blood-perfused rat lungs, also caused dose
      dependent sustained vasoconstriction, which could be attenuated with either
      calcium channel inhibition or a nitric oxide donor. It was demonstrated that the
      pressor effects of AMI were not due to release of histamine, serotonin,
      noradrenaline, or the activities of cycloxygenase or lipoxygenase. After AMI,
      hypoxic pulmonary vasoconstriction and the pressor actions of 5-HT and
      noradrenaline were diminished, possibly due to uptake inhibition. Activities of
      the endothelial-based enzymes, nitric oxide synthase and endothelin-converting
      enzyme, were undiminished. Large acute doses of AMI caused oedema with rupture of
      capillaries and alveolar epithelium. Chronic iprindole raised pulmonary artery
      pressure and right ventricle (RV)/left ventricle (LV) + septal (S) weight.
      Chronic AMI led to attenuation of the pressor action of 5-HT, especially when
      associated with chronic hypoxic-induced pulmonary hypertension. RV/LV+S weight
      increased, attributable to LV decline. The acute and chronic effects observed
      might have relevance to clinical overdose, while the attenuation of acute effects
      offers possible therapeutic options.

PMID- 12212967
TI  - Beta-adrenergic receptor-mediated growth of human airway epithelial cell lines.
AB  - Abnormal growth of airway epithelium and the resultant thickening of airway walls
      may produce narrowing of airway calibre, thereby contributing to deterioration of
      bronchoconstriction in chronic obstructive pulmonary disease (COPD). Beta2
      adrenergic agonists have been widely used for the treatment of COPD, but their
      effects on the growth of airway epithelial cells is unknown. Growth of three
      human airway epithelial cell lines was studied in vitro. Exposure to salbutamol
      in serum-free medium increased 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium-bromide reduction and intracellular deoxyribonucleic acid
      (DNA) contents in 16-human bronchial epithelium (16-HBE) cells and NCI-H292
      cells, but not in A549 cells. The growth-promoting effect of salbutamol in 16-HBE
      cells was equipotent to 10% foetal bovine serum and was inhibited by propranolol
      and a cyclic adenosine monophosphate (cAMP) antagonist, Rp-adenosine 3',5'-cyclic
      monophosphorothioate triethylammonium salt (Rp-cAMPS). Likewise, forskolin and 8
      bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) caused cell growth and DNA
      synthesis. Western blot analysis showed that salbutamol, forskolin, and 8-Br-cAMP
      each induced expression of the phosphorylated form of mitogen-activated protein
      (MAP) kinase, and that the salbutamol-induced phosphorylation was inhibited by
      propranolol, Rp-cAMPS, and the MAP kinase-kinase inhibitor PD98059. These results
      suggest that in certain airway epithelial cell lines stimulation of beta2
      adrenergic receptors and the consequent production of cyclic adenosine
      monophosphate may upregulate cell growth, probably through activation of the
      mitogen-activated protein kinase cascade.

PMID- 12212968
TI  - Resistance to Fas-mediated apoptosis in human lung fibroblast.
AB  - The current authors have demonstrated previously that epithelial cell apoptosis,
      induced by the Fas-Fas ligand pathway, might be involved in fibrosing lung
      diseases. Whereas lung epithelial cells are sensitive to the Fas-mediated
      apoptosis, lung fibroblasts may be resistant to Fas-mediated apoptosis and
      replace damaged epithelial cells. The WI-38 lung fibroblast cell line and primary
      lung fibroblasts were used to examine the resistant to Fas-mediated apoptosis and
      the association of anti-apoptotic proteins with this resistance. The
      administration of agonistic anti-Fas antibody (CH-11) or cycloheximide alone did
      not induce apoptosis, whereas the co-administration of CH-11 with cycloheximide
      induced apoptosis in WI-38 cells, in which caspase-8 and -3, but not -9, were
      activated, and X chromosome-linked inhibitor of apoptosis (ILP) and FLICE-like
      inhibitor protein (FLIP(L)), but not bcl-xL and bcl-2, were remarkably down
      regulated. Primary lung fibroblasts were also resistant to Fas-mediated
      apoptosis, and ILP and FLIP appeared to be involved in this resistance.
      Furthermore, the results of immunohistochemistry demonstrated that fibroblasts
      expressed ILP and FLIP(L) proteins in lung tissues from patients with idiopathic
      pulmonary fibrosis. These results suggest that anti-apoptotic proteins such as X
      chromosome-linked inhibitor of apoptosis and FLICE-like inhibitor protein may
      play an important role in preventing Fas-mediated apoptosis in lung fibroblasts,
      and participate in the development of pulmonary fibrosis.

PMID- 12212969
TI  - Tumour necrosis factor-alpha induced CD70 and interleukin-7R mRNA expression in
      BEAS-2B cells.
AB  - Over the past few years, evidence has emerged for the potential role of the human
      bronchial epithelial cell in the initiation and progress of inflammation of the
      airway. Thus, the aim of this study was to investigate the expression pattern of
      cytokines and immunomodulatory factors in the human bronchial epithelial cell. To
      elucidate this highly complex expression and regulation pattern, the simian virus
      40 transformed human bronchial-epithelial cell line BEAS-2B was stimulated with
      human recombinant tumour necrosis factor (hrTNF)-alpha (10 ng x mL(-1) (specific
      activity, 2.86 x 10(7) U x mg(-1))) and messenger ribonucleic acid (mRNA)
      expression pattern was analysed by complementary deoxyribonucleic acid (cDNA)
      array analysis. Among 375 arrayed cDNA clones, 173 (46%) were detected in BEAS-2B
      cells. The levels of expression of 17 genes, including those of monocyte
      chemoattractant protein (MCP)-1, intercellular adhesion molecule (ICAM)-1, growth
      related oncogene (GRO) alpha, beta, gamma, interleukin (IL)-7 receptor, CD70, IL
      6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and regulated
      in activation, normal T-cell expressed and secreted (RANTES) were elevated after
      TNF-alpha stimulation. The differential character of 12 clones was further
      characterised and verified by real time polymerase chain reaction (PCR) analysis
      of total ribonucleic acid (RNA) isolated from BEAS-2B cells after 4 or 16 h
      incubation with increasing TNF-alpha concentrations (1 pg-10 ng x mL(-1)). The
      authors semiquantified concentration-dependent mRNA upregulation of cytokines and
      immunology factors identified in the array and could determine threshold values
      of mRNA increases at 10 pg x mL(-1)-1 ng x mL(-1) TNF-alpha by real-time PCR. For
      CD70 (CD27 ligand) and interleukin-7 receptor, which to the best of the author's
      knowledge have not yet been described in the human bronchial epithelial cell, a
      rapid and continuous messenger ribonucleic acid increase induced by 100 pg x mL(
      1) tumour necrosis factor-alpha after only 60-90 min was shown. A potential role
      for these genes in the inflammatory process in the human bronchial epithelial
      cell is proposed.

PMID- 12212970
TI  - Enhanced IL-4 responses in children with a history of respiratory syncytial virus
      bronchiolitis in infancy.
AB  - Infants who recover from respiratory syncytial virus (RSV)-induced bronchiolitis
      are at high risk of developing asthma and recurrent wheezing. It is not known
      whether severe RSV infection itself causes persistent effects or is a marker of a
      "wheezy" predisposition. To determine the long-term immunological correlates of
      infantile bronchiolitis, interleukin (IL)-4 and interferon (IFN)-gamma responses
      to a panel of antigens were studied in a well-characterised cohort of 7-8-yr-old
      children with a history of severe RSV bronchiolitis in infancy. Peripheral blood
      lymphocytes from 37 children who were hospitalised with RSV bronchiolitis in
      infancy and from 69 age-, sex- and location-matched controls were stimulated in
      vitro with RSV, house-dust mite, birch and cat antigens. Cellular proliferation,
      and enzyme-linked immunoSPOT IFN-gamma and IL-4 production were measured. IL-4
      producing T-cells responding to RSV and cat antigens were significantly more
      frequent in exbronchiolitics. Other responses (including the IFN-gamma response
      to RSV) were equally strong in exbronchiolitics and controls. Respiratory
      syncytial virus infection primes memory T-cells that make interferon-gamma, but
      virus and aeroallergen-specific and interleukin-4 producing T-cells are also
      frequently primed in bronchiolitics. Respiratory syncytial virus bronchiolitis in
      infancy may increase the risk of allergic sensitisation by providing a local
      interleukin-4-rich environment, in which airborne allergens are first
      encountered.

PMID- 12212971
TI  - Perinatal predictors of respiratory symptoms and lung function at a young adult
      age.
AB  - A longitudinal cohort of 2,957 babies, born in 1975-1978, was used to investigate
      whether perinatal factors predict respiratory morbidity at a young adult age. In
      1997, the presence of asthmatic (wheeze, nocturnal dyspnoea) and bronchitic
      (cough, phlegm, dyspnoea grade 3) symptoms and the level of lung function was
      determined in this cohort. The independent association between smoking during
      pregnancy, being first-born, birth weight and respiratory symptoms and lung
      function at young adult age was investigated using multiple regression models,
      taking other potential risk factors into account. Of 1,568 responders, 608 (39%,
      aged 18-22 yrs) had at least one respiratory symptom. The young adults who had a
      mother that smoked during pregnancy had a significantly lower level of lung
      function than their nonintra-uterine exposed peers (regression coefficient (B)
      (standard error): peak expiratory flow (PEF) -0.257 (0.131) L x s(-1); forced
      expiratory flow when 25% of the forced vital capacity has been exhaled (FEF25) 
      0.290 (0.129) L x s(-1)), although they were not at increased risk of having
      respiratory symptoms. Young adults who were first-born had better levels of lung
      function (B (SE): forced expiratory volume in one second (FEV1) 0.090 (0.042) L)
      and were less likely to have asthmatic symptoms (odds ratio (95%, confidence
      interval): 0.58 (0.35-0.95)) than those not first-born. Low birth weight (FEV1 
      0.013 (0.004) L for a reduction of 100 g) was also predictive of reduced achieved
      levels of lung function at young adult age, independent of other potential risk
      factors, e.g. current smoking habits or familial predisposition. This study adds
      to the knowledge of the role of perinatal factors, such as smoking during
      pregnancy, as important predictors of respiratory morbidity.

PMID- 12212972
TI  - Fever episodes in early life and the development of atopy in children with
      asthma.
AB  - The hygiene hypothesis proposes that declining exposure to infections may
      contribute to the allergy and asthma "epidemic", but studies to identify the
      infections involved have so far provided conflicting data. An alternative
      approach could be based on an attempt to identify the mechanisms common to
      several different infections, which may exert an atopy "protective" effect. One
      of these mechanisms may be fever, which is frequently associated with infections
      and may stimulate the synthesis of interferon-gamma. The aim of this study was to
      test whether the frequency of fever episodes in the first years of life are
      related to the development of atopy. Asthmatic (cases, n=317) and nonasthmatic
      children (controls, n=304) attending the outpatients' allergy clinic were
      enrolled. The number of fever episodes in the first 2 yrs of life was
      retrospectively assessed by parental report via a questionnaire completed by
      interview. Atopy was determined by skin-prick tests to 10 prevalent inhalant
      allergens at the time of examination. Fever episodes in the first or in the
      second year of life were significantly more frequent among children with asthma.
      However, this difference was totally accounted for by a subgroup of children who
      started wheezing in the first 12 months of life. A significant inverse
      association between fever episodes in the first 12 months of life and atopy was
      found among cases, but not in controls. The association persisted after adjusting
      for age, sex, daycare attendance and family history of atopic disease and this
      was totally accounted for by asthmatic children who started wheezing after the
      first 12 months of life. No significant association was found between fever
      episodes in the second year of life and atopy for cases and controls. The data
      presented here suggests that fever episodes early in life may affect the natural
      history of asthma by preventing the development of atopy and highlights the need
      to monitor fever episodes of any kind in longitudinal studies aimed at
      investigating the hygiene hypothesis prospectively.

PMID- 12212973
TI  - Inpatient resource utilisation in younger (2-5 yrs) and older (6-14 yrs)
      asthmatic children in Finland.
AB  - Asthma is the most common chronic disorder among Finnish children, however, the
      economic burden of paediatric asthma in Finland has not yet been comprehensively
      evaluated. The objective of this study was to compare inpatient resource
      utilisation between younger (2-5 yrs) and older children (6-14 yrs) with asthma
      in Finland. A national database of inpatient resource utilisation was applied to
      determine use of hospital services among children with asthma in 1999. Regional
      estimates of charges were combined with hospitalisation episodes to determine
      total inpatient cost. The results indicate that younger asthmatic children
      consume 3-times more inpatient resources per capita. Incidence of first
      admissions because of asthma was 3-times higher in younger children.
      Hospitalisation and rehospitalisation rates were also 3- and 4-times higher,
      respectively. The total annual inpatient cost of asthma in children aged 2-5 and
      6-14 yrs was Euro 1.98 million with each group accounting for Euro 1.12 million
      and Euro 0.86 million, respectively. Regional and age-related differences in
      hospitalisation rates and costs were likely related to variable clinical practice
      on the primary level, difficulties with diagnosis and compliance among younger
      children.

PMID- 12212974
TI  - Domestic exposure to formaldehyde significantly increases the risk of asthma in
      young children.
AB  - Concern has arisen in recent years about indoor air pollution as a risk factor
      for asthma. Formaldehyde exposure was examined in relation to asthma among young
      children (between 6 months and 3 yrs old) in a population-based control study
      carried out in Perth, Western Australia, between 1997-1999. An association
      between exposure to formaldehyde and asthma in young children has been suggested.
      Cases (n=88), whose parents were recruited at Princess Margaret Hospital Accident
      and Emergency Dept (Perth, Western Australia), were children discharged with
      asthma as the primary diagnosis. Controls (n=104), who were children in the same
      age group without asthma diagnosed by a doctor, were identified from birth
      records through the Health Dept of Western Australia (Perth, Western Australia).
      Health outcomes for the children were studied using a respiratory questionnaire
      and skin-prick tests. Formaldehyde, average temperature and relative humidity
      were measured on two occasions, winter (July-September 1998) and summer (December
      1998-March 1999) in the child's bedroom and in the living room. The study found
      seasonal differences in formaldehyde levels in the children's bedrooms and living
      rooms with significantly greater formaldehyde exposure during the summer period
      for case and control subjects. The generalised estimating equation model showed
      that children exposed to formaldehyde levels of > or = 60 microg x m(-3) are at
      increased risk of having asthma. The results suggest that domestic exposure to
      formaldehyde increases the risk of childhood asthma.

PMID- 12212975
TI  - Bronchial challenge with flour: early response is dependent on the dose of
      activated allergen inhaled.
AB  - Specific bronchial challenges provide information about the relationship between
      inhaled dose of allergen and change in lung function, but the intermediate
      pathways remain largely obscure. The aim of this study was to investigate the
      relationships between the early asthmatic response and 1) the inhaled dose of
      wheat flour, 2) the concentration of wheat flour, 3) the duration of the
      exposure, and 4) the deactivation of inhaled allergens and mediators. Thirty-one
      patients with occupational asthma to wheat flour were studied. Particle aerosols
      were generated by a computer-controlled aerosoliser and the results were
      expressed as the provocative dose causing a 20% fall in forced expiratory volume
      in one second (FEVi) (PD20). The cumulative dose (from the beginning of the
      challenge), the last inhaled dose, and an estimated dose (taking into account
      exponential deactivation), were calculated. Twenty patients had high reactivity
      to flour (reaching a PD20 value). Eleven patients had intermediate reactivity (no
      measurable PD20 but significantly greater fall in FEV1 compared with lactose
      challenge). A better correlation between change in FEV1 and dose was obtained for
      the estimated dose than for the cumulative or last inhaled dose. The bronchial
      response to wheat flour can be measured by the individual specific
      hyperreactivity and is expressed by provocative dose of flour. However,
      deactivation of the allergen and mediators has to be taken into account. This
      problem can be addressed by using a mathematical model.

PMID- 12212976
TI  - Longitudinal analyses of chest radiographs from the European Carbon Black
      Respiratory Morbidity Study.
AB  - High levels of exposure to carbon black have been linked with an increased
      prevalence of chest radiograph abnormalities. However, it is unclear to what
      extent current levels of exposure in the carbon black manufacturing industry are
      associated with new cases of and progression in small opacities. Longitudinal
      analyses were carried out on data from workers in the European carbon black
      manufacturing industry who provided three full-size chest radiographs
      sequentially between 1987-1995. All chest radiographs were independently read by
      three experienced readers according to the International Labour Organisation
      (ILO) classification. After exclusion of participants with previous lung diseases
      or injuries, females, unreadable chest radiographs and from factories with a low
      participation rate, data from 675 workers were available for the longitudinal
      analyses. An association was observed between cumulative carbon black exposure
      and new cases of chest radiograph abnormalities (ILO category > or = 1/0) and
      progression in small opacities. These associations were mainly related to changes
      in chest radiographs from workers at one factory. A large percentage of workers
      with chest radiograph abnormalities reversed to normal chest films; however,
      after adjusting for other factors, this was not associated with levels of
      exposure to carbon black dust. In conclusion, the results show that exposure to
      carbon black is associated with increased risk of chest radiographic
      abnormalities, which may be reversible after reduction or cessation of exposure.

PMID- 12212977
TI  - Exhaled nitric oxide and bronchial responsiveness in healthy subjects exposed to
      organic dust.
AB  - Inhalation of organic dust from swine houses causes an intense inflammatory
      reaction in the respiratory tract, and increased bronchial responsiveness to
      methacholine in healthy subjects. The aims of the present study were to
      investigate whether exhaled nitric oxide (NO) is a marker of the inflammation
      caused by exposure to organic dust (swine dust), whether there is a relationship
      between an increase in exhaled NO and bronchial responsiveness, and also whether
      wearing a half-mask influences the airway reaction (assessed by exhaled NO) and
      the increased bronchial responsiveness. Thirty-three healthy nonatopic,
      nonsmoking subjects were exposed during 3 h of light work in a swine confinement
      building. Eleven of the subjects were wearing a half-mask and 22 were
      unprotected. Lung function, bronchial responsiveness and exhaled NO were measured
      before and after exposure. The provocative concentration causing a 20% fall in
      forced expiratory volume in one second fell by 2.7 (2.1-4.1) (median (25th-75th
      percentiles)) doubling concentration steps in subjects without a half-mask and by
      1.5 (0.9-2.9) doubling concentration steps in subject wearing a mask. Exhaled NO
      increased from 7.5 (5.7-13.7) parts per billion (ppb) before to 13.4 (10.5-17.5)
      ppb after exposure in the unprotected group and was unaltered (8.3 (6.1-14.1) to
      8.6 (6.6-14.6) ppb) in the group wearing a half-mask. There was no correlation
      between NO increase and provocative dose causing a 20% fall in the forced
      expiratory volume in one second decrease. In conclusion, bronchial responsiveness
      and exhaled nitric oxide increased after exposure to a swine confinement
      facility. Half-mask abolished the increase in exhaled nitric oxide levels, but
      influenced the increase in bronchial responsiveness to a minor extent. These
      results indicate that these two outcome measures reflect different aspects of
      airway inflammation induced by exposure to a farming environment.

PMID- 12212978
TI  - Hospital-acquired pneumonia: microbiological data and potential adequacy of
      antimicrobial regimens.
AB  - Adequate antimicrobial therapy is a main approach employed to decrease the
      mortality associated with hospital-acquired pneumonia (HAP). All methods that
      optimise empirical treatment without increasing antibiotic selective pressure are
      relevant. Categorisation of patients according to HAP time of onset, severity and
      risk factors (American Thoracic Society (ATS) classification) or duration of
      mechanical ventilation and prior antibiotics (Trouillet's classification) are two
      such methods. The aim of this study was to catagorise patients with HAP according
      to these classifications and to determine the frequency of resistant pathogens
      and the most adequate antimicrobial regimens in each group. A total 124 patients
      with bacteriologically proven HAP were studied. The ATS classification
      categorised patients by increasing frequency of resistant pathogens from 0-30.3%.
      The ATS empirical antibiotic recommendations appeared valid but proposed
      combinations including vancomycin for 72.5% of patients. Trouillet's
      classification categorised patients into four groups with a frequency of
      resistant pathogens from 4.9-35.6%. Vancomycin was proposed for 48.5% of
      patients. The American Thoracic Society classification appears to be more
      specific than Trouillet's for predicting the absence of resistant causative
      pathogens in hospital-acquired pneumonia but could lead to a greater use of
      vancomycin. Stratification combining the two classifications is an interesting
      alternative.

PMID- 12212979
TI  - Side-effects of antituberculosis drug treatment in patients with chronic renal
      failure.
AB  - Patients with chronic renal failure (CRF) have a high incidence of tuberculosis
      (TB). Those from the Indian subcontinent are at particular risk. The frequency of
      side-effects associated with antituberculous treatment in a group of patients
      with CRF was studied. All cases of TB in patients with CRF occurring over a 13-yr
      period at the Manchester Royal Infirmary, from 1986-1999, were identified by
      diagnostic coding, microbiology records and a TB database. The case notes were
      then reviewed. Twenty-four cases were identified, eight predialysis and 16
      requiring regular dialysis. TB occurring in the dialysis group was extrapulmonary
      in every case. Nineteen of 24 (79%) patients were of Indian subcontinent origin
      and 14 of 16 (87%) dialysis patients were non-Caucasian. Adverse effects of
      treatment occurred in two of eight (25%) in the predialysis group and nine of 16
      (56%) of the dialysis group. These were most commonly neuropsychiatric (6),
      hepatic (4) and gastrointestinal (4). Neuropsychiatric symptoms occurred
      exclusively in dialysis patients. In conclusion, a high incidence of side-effects
      from antituberculous medication, especially neuropsychiatric, hepatic and
      gastrointestinal, was identified in patients with chronic renal failure. Careful
      monitoring for side-effects is essential in this group, and consideration should
      be given to administering antituberculous chemoprophylaxis to all high-risk
      groups.

PMID- 12212980
TI  - Some factors affecting cerebral tissue saturation during obstructive sleep
      apnoea.
AB  - Measurement of cerebral tissue saturation during obstructive sleep apnoea (OSA)
      may provide additional information to conventional peripheral oxygen saturation.
      Thirteen subjects with OSA (mean apnoea/hypopnoea index 65.7+/-27.9) were
      monitored using full polysomnography and monitoring of near-infrared cerebral
      tissue oxygenation index (TOI). One-thousand and thirty-six apnoeas and
      hypopnoeas were analysed, in terms of duration, sleep stage, arterial oxygen
      saturation (Sa,O2) dip, minimum Sa,O2, TOI dip and minimum TOI. Cerebral TOI is a
      measure of cerebral tissue saturation of haemoglobin with oxygen, calculated
      using near-infrared spatially resolved spectroscopy, which has been shown to have
      a high specificity for intracranial changes. Decreases in cerebral oxygenation
      were observed during apnoeas and hypopnoeas. Baseline TOI ranged from 50.1-73.0%
      and mean apnoea/hypopnoea related TOI dips ranged from 1.43-6.85%. Mean Sa,O2
      dips varied from 3.8-21.7%. In regression analysis, factors significantly
      predicting the magnitude of the TOI dip were Sa,O2 dip, minimum Sa,O2, apnoea
      duration and rapid eye movement sleep stage. The effect of apnoea duration and
      sleep stage remained significant after Sa,O2 was included in the regression
      equation. Near-infrared spectroscopy provides a noninvasive technique for
      monitoring cerebral tissue saturation during obstructive sleep apnoea.

PMID- 12212981
TI  - Effect of surfactant on pharyngeal mechanics in sleeping humans: implications for
      sleep apnoea.
AB  - Instillation of surfactant into the pharyngeal lumen reduces the pressure
      required to reopen an occluded airway, and decreases the apnoea/hypopnoea index
      (AHI). The authors hypothesised that surfactant also reduces the sleep-related
      increase in pharyngeal resistance. To test this hypothesis two single blind,
      crossover, placebo-controlled studies were performed. In protocol A seven male,
      asymptomatic snoring subjects were studied during sleep. Inspiratory pharyngeal
      resistance was calculated from plots of airflow versus supraglottic pressure
      (seven breaths) before and after surfactant or saline instillation. In protocol
      B, in a different group of seven male subjects with sleep apnoea (AHI 15.2 (12)
      events x h(-1)) the effect of surfactant or saline on sleep disordered breathing
      was measured, for 1 h immediately before and after surfactant or saline
      instillation. Surfactant decreased pharyngeal resistance calculated at peak
      pressure (group mean (SD): pre versus post 83.7 (76.4) versus 49.4 (71.1) cmH2O x
      L(-1) x s(-1)) and significantly reduced the respiratory disturbance index (RDI
      pre versus post 79.7 (58.7) versus 59.6 (56.9) events x h(-1)). Saline did not
      decrease resistance (pre versus post 58.6 (31.1) versus 72.5 (73.4) cmH2O x L(-1)
      x s(-1)) or RDI (pre versus post 75.3 (42.4) versus 79.9 (46.1) events x h(-1)).
      Surfactant reduced the collapsibility of the pharynx and led to a modest
      reduction in respiratory disturbance index. The authors speculate that surfactant
      may delay occlusion by reducing the liquid "bridging" within the folded
      pharyngeal lining.

PMID- 12212982
TI  - Upregulation of nerve growth factor expression by human airway smooth muscle
      cells in inflammatory conditions.
AB  - Recent studies have suggested that nerve growth factor (NGF) may play a role in
      inflammation and bronchial hyperresponsiveness in asthma. Neither the types of
      cells that produce NGF in the human airways nor the effect of inflammation on NGF
      expression are clear. The two-fold aim of the present study was to determine
      whether airway smooth muscle produces NGF in vitro, and, if so, whether the pro
      inflammatory cytokine interleukin-1beta (IL-1beta) affects this expression. Human
      airway smooth muscle cells in culture were incubated in the presence or absence
      of IL-1beta. NGF production was measured by enzyme-linked immunosorbent assay.
      NGF messenger ribonucleic acid (mRNA) was measured using a specific real-time
      fluorescent polymerase chain reaction technique, and expressed in relation to
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels. Human airway smooth
      muscle cells in vitro expressed NGF constitutively (21.4+/-7.8 pg x mL(-1);
      14.6+/-5.4 pg NGF complementary deoxyribonucleic acid (cDNA) x pg GAPDH cDNA(-1)
      (mean+/-SEM)). Stimulation with IL-1beta (0.1-30 U x mL(-1)) for 24 h induced a
      dose-dependent increase in NGF production (22.1 pg x mL(-1) at 10 U x mL(-1);
      p<0.05). The IL-1beta (10 U x mL(-1))-induced increase in NGF expression was time
      dependent. It was highest for NGF protein at 10 h (1.6-fold increase over
      control; p<0.001) and for NGF mRNA at 2.5 h (2.4-fold increase over control;
      p<0.05). In conclusion, the present study clearly shows that the human airway
      smooth muscle cell is a source of nerve growth factor, the expression of which is
      upregulated in inflammatory conditions, mimicked in vitro by the addition of
      interleukin-1beta.

PMID- 12212983
TI  - The Liverpool Lung Project: a molecular epidemiological study of early lung
      cancer detection.
AB  - Lung cancer is the major cause of death from neoplastic disease in the world, and
      even with politically-motivated smoking cessation campaigns throughout Europe,
      the disease remains the major cause of death. The development of molecular
      epidemiological population-based research into early lung cancer detection, such
      as the Liverpool Lung Project (LLP), may provide a way forward. This is the first
      major molecular epidemiological study of detection of early lung cancer. The use
      of molecular epidemiological risk assessments prior to clinical diagnosis and
      markers of preclinical carcinogenesis in patients with a high risk of developing
      lung cancer will reduce the incidence of clinically-detectable lung cancer, given
      the appropriate intervention strategies. The aims are as follows: 1) to prepare a
      molecular genetic and epidemiological risk assessment model based on
      environmental exposures and genetic predisposition; 2) to develop an archive of
      specimens relating to at-risk individuals and those with lung cancer; 3) to
      redefine lung cancer based on molecular pathology using the fields of expression
      profiling, genetic instability and molecular cytogenetics; 4) to identify and
      assess novel markers of precarcinogenesis in high-risk populations; and 5) to
      facilitate the development of new treatment strategies (e.g. chemoprevention
      programmes and targeted drug therapies). The LLP has two components: 1) a case
      controlled study of newly-diagnosed cases of lung cancer that will provide a
      baseline, risk assessment; and 2) a prospective cohort study to be carried out
      over a 10-yr period that will identify markers of preclinical carcinogenesis. In
      depth interviews are carried out using structured and semi-structured
      questionnaires. Sputum, blood and tumour specimens are collected and will be
      assessed for specific molecular markers (e.g. genetic instability, mutation and
      expression profiling, and methylation status). Conclusions from The Liverpool
      Lung Project will be based around molecular-epidemiological and genotyping risk
      assessment models, as well as redefining the disease, and ultimately contributing
      to the development of new early lung cancer detection and treatment strategies.

PMID- 12212984
TI  - Noninvasive ventilation for chest wall and neuromuscular disorders.
AB  - Neuromuscular and chest wall disorders are individually uncommon but together
      form an important group of conditions that can lead to chronic ventilatory
      failure. This is best recognised in scoliosis, kyphosis, following a
      thoracoplasty, in muscular dystrophies, such as Duchenne muscular dystrophy
      (DMD), and myotonic dystrophy, after poliomyelitis and with motor neurone disease
      (amyotrophic lateral sclerosis). If bulbar function is impaired, tracheostomy
      ventilation may be required, but in other situations, noninvasive ventilation is
      preferable. Positive pressure techniques using nasal and face masks are usually
      the first choice, but negative pressure ventilation is an alternative. There are
      no randomised-controlled trials regarding the indications for initiating
      noninvasive ventilation, but this is usually provided if there are symptoms due
      to nocturnal hypoventilation or right heart failure in the presence of a raised
      carbon dioxide tension in arterial blood (Pa,CO2) either at night or, more
      usually, in the daytime as well. There is no evidence that "prophylactic"
      ventilatory support is of benefit if this is provided before ventilatory failure
      has appeared. Careful selection of patients is required, especially in the
      presence of progressive neuromuscular disorders such as DMD and motor neurone
      disease. There are no randomised-controlled trials concerning the outcome of
      noninvasive ventilation in these conditions, but studies have shown an improved
      quality of life, physical activity and haemodynamics, normalisation of blood
      gases and slight improvement in other physiological measures, such as the vital
      capacity and maximal mouth pressures. Survival in chest wall disorders is
      approximately 90% at 1 yr and 80% at 5 yrs, and similar figures have been
      obtained in nonprogressive neuromuscular conditions. If, however, the underlying
      disorder is deteriorating, particularly if it involves the bulbar muscles, it may
      limit survival despite the provision of adequate noninvasive ventilatory support.

PMID- 12212985
TI  - Adenosine-receptor subtypes: their relevance to adenosine-mediated responses in
      asthma and chronic obstructive pulmonary disease.
AB  - Adenosine administration by inhalation elicits concentration-related
      bronchoconstriction in subjects with asthma and chronic obstructive pulmonary
      disease (COPD). The mechanisms of adenosine-induced bronchoconstriction appear to
      involve a selective interaction with activated mast cells with subsequent release
      of preformed and newly-formed mediators. Further evidence linking adenosine
      signalling to asthma and COPD comes from the finding that many cell types that
      play important roles in the exacerbation of these conditions express adenosine
      receptors and demonstrate relevant effects through stimulation of these
      receptors. Therefore, blockade of these receptors may be a valuable approach to
      the treatment of asthma and chronic obstructive pulmonary disease. Promising
      adenosine-receptor targets for novel therapeutics of asthma and chronic
      obstructive pulmonary disease have recently been identified in a number of
      inflammatory cell types, including mast cells, eosinophils, lymphocytes,
      neutrophils, and macrophages. The recent characterisation of the A2B receptors
      indicates the human lung mast cell as one of the most strategic cellular targets.

PMID- 12212986
TI  - Weakness of respiratory and skeletal muscles after a short course of steroids in
      patients with acute lung rejection.
AB  - There have been occasional reports of acute respiratory and skeletal muscle
      weakness in intensive care unit patients treated with massive doses of
      corticosteroids. However, in this setting the concomitant use of other drugs may
      have influenced the finding. In this study the effects of 5 days of treatment
      with high doses of steroids in consecutive patients with acute lung rejection
      after transplantation were systematically evaluated. Maximal inspiratory pressure
      during phrenic nerve stimulation and peak torque of isokinetic contraction of the
      quadriceps and hamstring muscles were measured objectively. Compared to the
      pretreatment condition, approximately 45% of patients showed acute generalised
      muscle weakness that recovered after approximately 2 months. This demonstrates
      muscle weakness induced by steroids within patients.

PMID- 12212987
TI  - An infant with respiratory distress and failure to thrive.

PMID- 12212988
TI  - Serological evidence of Legionella species infection in acute exacerbation of
      COPD.

PMID- 12212990
TI  - Time-variant investigation of quadratic phase couplings caused by amplitude
      modulation in electroencephalic burst-suppression patterns.
AB  - OBJECTIVE: Several studies suggest that parameters derived from bispectral
      analysis of the EEG can be used to characterize specific cortical activation
      states represented by non linear interaction between brain electrical
      oscillations. For example, it was shown that so-called bispectral indices can be
      used to assess the depth of sedation. The methods applied so far are based on
      interval-related procedures of bispectral analysis. Consequently, the use of the
      resulting parameters for on-line monitoring or investigations of signal
      properties during transition periods, e.g., when entering burst-suppression
      periods, is restricted. The objective of this paper is to provide the
      methodological basis for a time-continuous (on-line) investigation of quadratic
      phase coupling induced by amplitude modulation. METHODS: To accomplish this aim
      an algorithm is presented which enables the analysis of the temporal development
      in the degree of amplitude modulation (DAM), e.g., during the transition to burst
      suppression periods in patients with severe neurological diseases. RESULTS: It
      was found that these periods are associated with increasing DAM compared with the
      baseline conditions.

PMID- 12212989
TI  - Arguing for the need of triangulation and iteration when designing medical
      equipment.
AB  - OBJECTIVE: There is a need to develop adequate methods for use by the
      manufacturers of medical equipment when specifying requirements for their
      development and in order for hospitals to critically assess their usability
      qualities before purchase. A Human Factors approach was used to determine
      requirements for the redesign of an existing volumetric infusion pump. With these
      requirements as a starting point, a new user interface for an infusion pump was
      designed. Usability tests were carried out to verify whether the new interface
      had better usability than the existing interface or whether further improvements
      were needed. This paper has two aims: 1) to compare the nature of the
      requirements derived from a Human Factors approach and from usability tests and
      2) to evaluate the use of usability tests on existing medical equipment as a
      basis for redesign and for evaluating the redesign. METHOD: The user requirements
      derived from the Human Factors approach were compared with the user requirements
      derived from the usability tests. RESULTS: The results show that the requirements
      derived from the Human Factors approach adequately covered contextual aspects of
      use. However, to derive requirements for a specific and operational level,
      usability tests must be conducted on existing equipment and prototypes. This
      study indicates that usability tests on existing medical equipment as a basis for
      redesign give a better understanding of problems with existing equipment.
      Moreover it is important to carry out usability tests to evaluate a redesign and
      find a satisfying solution. Expert users of the equipment had the experience,
      competence and confidence to be critical and suggest improvements based on their
      practical knowledge. The novice users on the other hand were important test users
      as they uncovered most of the serious handling problems and also committed most
      errors. CONCLUSION: The requirements derived from the Human Factors approach and
      the usability tests are important for the development of a new and improved user
      interface. The requirements derived from the Human Factors approach can be
      attributed to contextual requirements. The requirements derived from the
      usability tests have a higher degree of concreteness, are more specific and focus
      more on design solutions compared to the requirements derived from the Human
      Factors approach. It is important to consider intended user groups when carrying
      out usability tests, as the nature of the information from the different groups
      can be different.

PMID- 12212992
TI  - New possibilities in prognostication of hemodynamic instability during surgical
      operations.
AB  - The new approach to intraoperative hemodynamics disorders prognostication which
      caused of inadequate anaesthesiological protection is presented in this research.
      Hemodynamic parameters stability both with systemic homeokinesis state were
      investigated in 28 patients with various surgical diseases. Their surgical
      operations were carried out with either of combinatory inhalation anaesthesia
      (halothane and neuroleptics) or noninhalation neuroleptnarcasis with ketamine.
      Instability of homeostatic regulation was controlled with special original
      analysis of cardiac rhythm entropy dynamics chaotisity in multidimensional faze
      space of existence. It is established that numerical criterion of cardiac rhythm
      chaotic state degree exceeds the intended acceptable level 5-10 minutes before
      clinical signs of hemodynamics instability developing in all inadequate
      anaesthesiological protection cases.

PMID- 12212991
TI  - Automatic analysis and monitoring of burst suppression in anesthesia.
AB  - OBJECTIVE: We studied the spectral characteristics of the EEG burst suppression
      patterns (BSP) of two intravenous anesthetics, propofol and thiopental. Based on
      the obtained results, we developed a method for automatic segmentation,
      classification and compact presentation of burst suppression patterns. METHODS:
      The spectral analysis was performed with the short time Fourier transform and
      with autoregressive modeling to provide information of frequency contents of
      bursts. This information was used when designing appropriate filters for
      segmentation algorithms. The adaptive segmentation was carried out using two
      different nonparametric methods. The first one was based on the absolute values
      of amplitudes and is referred to as the ADIF method. The second method used the
      absolute values of the Nonlinear Energy Operator (NLEO) and is referred to as the
      NLEO method. Both methods have been described earlier but they were modified for
      the purposes of BSP detection. The signal was classified to bursts, suppressions
      and artifacts. Automatic classification was compared with manual classification.
      Results. The NLEO method was more accurate, especially in the detection of
      artifacts. NLEO method classified correctly 94.0% of the propofol data and 92.8%
      of the thiopental data. With the ADIF method, the results were 90.5% and 88.1%
      respectively. CONCLUSIONS: Our results show that burst suppression caused by the
      different anesthetics can be reliably detected with our segmentation and
      classification methods. The analysis of normal and pathological EEG, however,
      should include information of the anesthetic used. Knowledge of the normal
      variation of the EEG is necessary in order to detect the abnormal BSP of, for
      instance, seizure patients.

PMID- 12212993
TI  - A computerized method to measure systolic pressure variation (SPV) in
      mechanically ventilated patients.
AB  - INTRODUCTION: Intrathoracic pressure variation during mechanical ventilation has
      different effects on cardiac preload and stroke volume in both ventricles.
      Changes in left ventricle stroke volume are reflected by fluctuations of the
      arterial pressure waveform or Systolic Pressure Variation (SPV). SPV has been
      proposed as a way to evaluate vascular volume status in mechanically ventilated
      patients as well as responsiveness of the left ventricle stroke volume to volume
      loading. OBJECTIVE: In this paper an automated system is presented which is
      designed in order to provide physicians with information on SPV in mechanically
      ventilated patients. Methods. The developed system acquires the pressure
      transducer signal and analyses the pressure waveform in order to detect and
      identify the hemodynamic changes. Five patients underwent the clinical protocol
      in order to evaluate the software reliability. Each patient underwent
      measurements with positive end-expiratory pressure (PEEP) equal to 0 cm H2O, at
      an increase of 30% tidal volume, and at 15 cm H2O of PEEP, before and after
      infusion of 7 ml/kg of colloid solution. RESULTS: The reliability of the
      automated procedure has been verified by comparing the obtained results with data
      collected manually in order to test on whether the new method data are correlated
      with the conventional procedure. Our results show that in the worst case when the
      widest range for the limits of agreement is considered, the error is within 15%.
      CONCLUSIONS: The automated SPV measurement requires less time as well as human
      errors compared to the manual method; this makes SPV calculation a competitive
      alternative to methods for the measurements of stroke volume variations as
      arterial thermodilution technique and transesophageal echocardiography, which
      require sophisticated equipment and specific experience.

PMID- 12212994
TI  - Noninvasive cardiac output assessment during heart surgery.
AB  - OBJECTIVE: To evaluate the reliability of a new noninvasive method for the
      assessment of cardiac output with the partial carbon dioxide rebreathing
      technique. METHODS: This technique was applied to patients undergoing heart
      surgery. Values of cardiac index obtained with this equipment were compared with
      the artero-venous CO2 gradient, a reliable index of cardiovascular status.
      Positive and negative predictive values of the test were assessed. RESULTS: A
      total of 21 simultaneous measurement of the cardiac index and of the artero
      venous CO2 gradient were obtained. The positive predictive value of the test was
      67% while the negative predictive value was 100%, indicating that a normal value
      of cardiac index recorded with the rebreathing technique predicts with a good
      reliability a normal cardiovascular state. CONCLUSIONS: Working through a series
      of mathematical algorithms, accuracy in the computation of cardiac output can be
      decreased with this equipment; however, this limitation seems to be outweighed by
      the simplicity and noninvasive nature of the methods.

PMID- 12212995
TI  - Peripheral blood flow with a sedative propofol-ketamine combination.

PMID- 12212996
TI  - A comparison of two impedance cardiographs using head-up tilting and trend
      analysis.
AB  - OBJECTIVES: To compare the performances of two impedance cardiographs, the
      RheoCardioMonitor (RCM) and the BoMed NCCOM3, using trend analysis. This involved
      a series of head-up tilts, a simulation of the stroke volume (SV) and cardiac
      output (CO) response, calculation of prediction errors and cumulative sums
      (Cusum). METHODS: Eight healthy male volunteers, aged 27-37 years, were tilted on
      four occasions to angles of 55 degrees, 15 degrees, 30 degrees and 55 degrees,
      whilst recording SV and CO every 10-sec. Baseline and percentage changes with
      tilting were calculated. A simulation of the tilt response was constructed, and
      from this residuals (observed-predicted) and prediction errors ((observed
      predicted)/predicted) x 100% were calculated at 10-sec intervals. Trend analysis
      was performed by multiple analysis of the variance of serial measurements and
      graphically assessing changes in serial SV prediction errors, using Cusums.
      Results are presented as mean (range or SD). RESULTS: Baseline values for RCM-SV
      were 76 (35-94) ml and for CO 4.7 (2.8-6.1) litre x min(-1). For BoMed-SV they
      were 113 (90-164) ml and for CO 7.2 (5.5-11.9) litre x min(-1). Head-up tilting
      to 55 degrees resulted in a 32 (12)% decrease in RCM-SV and a 21 (11)% decrease
      in BoMed-SV (p < 0.01). Prediction errors for RCM-SV were (6.5 (4.9)%) and for
      BoMed-SV (6.8 (5.2)%) (p = 0.048). Cusum analysis showed that in 84% of tests,
      impedance measurements remained within +/- 10% of the initial calibration. There
      was no difference between devices (chi2 = 0.92). CONCLUSIONS: Simulation of a
      physiological response, such as that to head-up tilting, and using a trend
      analysis based on prediction errors and Cusum, is a useful technique. The
      trending abilities of the RCM and BoMed were similar.

PMID- 12212997
TI  - Validity of gastric intramucosal pH (pHi) for circulatory evaluation in pediatric
      patients.
AB  - OBJECTIVE: To determine if the measurement of gastric intramucosal pH (pHi) is
      useful for evaluation of circulatory status of critically ill pediatric patients.
      DESIGN: Prospective clinical study. SETTING: General intensive care unit in a
      university hospital. PATIENTS: Seven pediatric patients (mean age: 2 y.o.); six
      post-cardiac surgery, one receiving barbiturate therapy. INTERVENTIONS:
      Tonometric catheters were placed via nasogastric approach. pHi was measured after
      confirmation of the catheter position by X-ray. MEASUREMENTS AND MAIN RESULTS:
      Saturation of venous blood oxygen (SvO2), arterial keton body ratio (AKBR), serum
      lactate level and pHi were evaluated simultaneously. No patients survived with
      pHi below 7.22; pHi above 7.11 significantly correlated with SvO2 values (r =
      0.814, p < 0.001); pHi below 7.11 did not show any significant correlation with
      SvO2. Whereas SvO2 values of under 40% were distributed in the pHi range from
      7.11 to 7.19, pHi below 7.11 occurred when SvO2 values were more than 40%. AKBR
      and serum lactate level did not correlate with pHi. CONCLUSION: pHi can be a
      useful parameter for evaluating the circulatory status of critically ill
      pediatric patients; it allows reliable evaluation of splanchnic and peripheral
      perfusion.

PMID- 12212998
TI  - Enamel nail polish does not interfere with pulse oximetry among normoxic
      volunteers.
AB  - OBJECTIVE: To determine if enamel nail polish interferes with pulse oximetry.
      DESIGN: Laboratory investigation. PARTICIPANTS: 12 healthy nonsmoking volunteers.
      METHODS: Spectrophotometry was performed on polystyrene cuvettes painted with 3
      uniform layers of nail polish enamel in triplicate. Absorbances were compared at
      660 and 940 nm for 10 colors across the visible spectrum and documented by the
      Institute of Electrical and Electronic Engineers color code against Pantone
      matches on a color scanner. Colors were then selected that had the greatest A660
      A940 difference and pulse oximetry (Nellcor N-209A. Pleasanton , CA) was
      performed on nails painted with these colors on 12 subjects using an unpainted
      digit as a control. RESULTS: When tested by the oximeter, there were no SpO2
      differences detected between nail polish colors, nor were there any differences
      between the painted and the unpainted control digits across subjects (F = 0.51,
      ANOVA; p = 0.67). Blue (B), green (G), and lime green (G') possessed the largest
      A660-A940 difference and potentially could interfere with pulse oximetry but did
      not do so in the clinical model. CONCLUSION: Enamel finger nail polish pigments
      do not interfere with pulse oximetry as previously reported, the A660-A940
      difference must be greater than 1.88 +/- 0.23 SD AU in order to affect pulse
      oximetry.

PMID- 12212999
TI  - Comparative provocation test of respiratory monitoring methods.
AB  - OBJECTIVE: The aim of this study was to compare clinically relevant performance
      of: 1) a prototype respiratory sensor based on capnometry with two alternative
      signal receptor fixations, 2) a fiberoptic humidity sensor and 3) human visual
      observation. Comparative provocation tests were performed on volunteers at the
      Post-Anesthesia Care Unit at Vasteras Central Hospital. METHODS: The experimental
      tests involved 10 healthy, voluntary test subjects, instructed to intersperse
      normal breathing with protocol provocations of breath holding, limb and head
      movements, and nasal oxygen supplement. The signal outputs from the three
      respiratory monitoring methods were recorded on a personal computer. The signal
      analysis included visual categorising of the signals and counting breath events.
      Recognising that none of the methods could act as reference, events were
      classified as "unanimous," "majority" or "minority" events depending on how many
      of the three methods that detected a breath. RESULTS: The average total recording
      time was 37 minutes per subject. The respiratory rates varied from 6.5 to 19
      breaths per minute, with a mean value of 11.4 breaths/minute. The breath hold
      duration ranged from 18 to 50 seconds. Discrepancies between the three methods
      were found in more than 20% of the marked events. The most frequent majority
      events were due to events not recorded by the observer who, on the other hand,
      contributed the least to minority events. The provocations made by the subjects
      during the measurement did not increase the rates of majority and minority
      events, compared to periods of no provocation. The fiberoptic device exhibited a
      larger count of minority events but a smaller contribution to majority events
      than the capnometry prototype. CONCLUSIONS: The capnometry and fiberoptic sensors
      exhibit differences in responses that may be understood from basic principles.
      The importance of the physical application of the sensor to the patient was
      clearly observed. The optimum design remains to be found.

PMID- 12213000
TI  - Repositioning dentistry.

PMID- 12213001
TI  - Mercury residue.

PMID- 12213002
TI  - Rubber dam in endodontics.

PMID- 12213003
TI  - Gingival recession.

PMID- 12213004
TI  - Practice of UK dentistry.

PMID- 12213005
TI  - Access to the GDS.

PMID- 12213006
TI  - Duty of care.

PMID- 12213007
TI  - Crowns and other extra-coronal restorations: resin-bonded metal restorations.
AB  - Resin-bonded metal restorations is the final part of the series. Cast metal
      restorations which rely on adhesion for attachment to teeth are attractive
      because of their potential to be much more conservative of tooth structure than
      conventional crowns which rely on preparation features providing macromechanical
      resistance and retention.

PMID- 12213008
TI  - The management of porphyria in dental practice.
AB  - From time to time a patient may attend your practice with a systemic condition
      that you may or may not remember from the small print of your undergraduate text
      books. This paper describes one such systemic condition, porphyria, and its
      dental management. This paper also describes the use of relative analgesia as an
      aid to anxiety management in porphyria.

PMID- 12213009
TI  - Effectiveness of microabrasion technique for improvement of dental aesthetics.
AB  - OBJECTIVES: To investigate which types of enamel opacity are effectively treated
      by the microabrasion technique and whether this technique could be used as a
      diagnostic aid to determine the aetiology of these defects. MATERIALS AND METHOD:
      Thirty two patients who had enamel opacities affecting both upper central
      incisors were selected and the disfigurements were classified into four types:
      single line, multi-line, patched and diffused. The patient's previous medical
      history, possible history of fluoride ingestion, presence of taurodontism and
      family history of similar enamel defects were recorded. Both incisors were
      treated with Prema abrasive paste mixed with 18% hydrochloric acid. The aesthetic
      improvements were assessed by the patients and their parents and their
      satisfaction level after the treatment was recorded. RESULTS: Approximately two
      thirds (65.6%) of the patients were satisfied with their appearance after
      microabrasion. Apart from four patients, the improved appearance was stable and
      acceptable to the remaining patients at the six month recall. Statistical
      analysis showed that acceptable improvement was found in patients with single
      line/patched types of defects but not in multi-line/diffused types (P = 0.03).
      However, the aesthetic improvement was not related to the patient's fluoride
      history, presence of taurodontism or the family history of enamel defects.
      CONCLUSION: Microabrasion using Prema abrasives with 1 8% HCI is effective in
      improving the appearance of enamel with single-line or patched opacities,
      indicating that these defects are a surface phenomenon. For the multi-line and
      diffused types, the defects appear to extend deeper into the enamel. The
      technique failed to assist in determining the aetiology of these defects.

PMID- 12213010
TI  - The way forward for dental sedation and primary care?
AB  - OBJECTIVES: Firstly to determine the current provision of sedation in primary
      dental care in an area of Scotland without local secondary care support and
      secondly, to investigate dental practitioners' desire for formal postgraduate
      training in sedation techniques. DESIGN: A prospective postal questionnaire-based
      study. SETTING: Grampian Primary Care NHS Trust, UK, 2001. SUBJECTS:
      Questionnaires were sent to all NHS dental practitioners and community dental
      service clinicians (N = 194] employed through Grampian Primary Care NHS Trust,
      Scotland during March - April 2001. The questionnaires sought details about
      personal status and the use and perceived need for conscious sedation techniques
      in practice in addition to the stated desire for postgraduate training in
      sedation techniques. RESULTS: One hundred and thirty-six questionnaires were
      returned (70%). Forty-nine per cent of respondents reported current sedation use,
      with intravenous sedation the favoured technique (82%), followed by oral sedation
      (33%) and inhalation sedation (19%). Seventy-four per cent of participants
      considered that there was a need for sedation in their own practice and 68% were
      interested in further postgraduate training in sedation techniques. CONCLUSION:
      Nearly three-quarters of practitioners who responded felt that there was a need
      for sedation in their own practice, although less than half were able to offer
      sedation to their patients. Nearly 70% of practitioners felt there was a need for
      postgraduate training in sedation techniques.

PMID- 12213012
TI  - Leaving it all behind.

PMID- 12213011
TI  - A novel approach to promoting change in SHO training in a dental teaching
      hospital.
AB  - An action research study using a series of staged focus groups with senior house
      officers (SHOs) and educational supervisors (ES) was used to identify the
      perceptions of the strengths and challenges in the SHO training programme and to
      indicate areas for improvement. The basic findings were not entirely surprising,
      with SHOs wanting more detailed feedback from educational supervisors and
      educational supervisors challenged (by time constraints and competing clinical
      and research responsibilities) in meeting the expectations of the SHOs. However
      the novel approach of using staged focus groups enhanced the educational
      supervisors' perception of the SHOs' view of their training and the SHOs'
      perception'of the challenges faced by educational supervisors. Thus a culture of
      dialogue was created which supported change and innovation. This process was able
      to directly inform and influence the development of a new induction programme for
      SHOs and provide valuable insight into the use of the portfolio of learning and
      the provision of study opportunities. These findings may only be of local
      interest, however the method employed can be transferred to other contexts to
      support a grass roots approach to change. Indeed, since this study has been
      completed, the method has been replicated in a medical setting.

PMID- 12213013
TI  - Determination of crystal polarity from bend contours in transmission electron
      microscope images.
AB  - A new method for determining the polarity of crystals with sphalerite structure
      (GaAs, GaSb, InP, etc.) within the transmission electron microscope (TEM) is
      presented. The method is derived from an established convergent beam electron
      diffraction (CBED) method (J. Appl. Crystallogr. 15 (1982) 60) and exploits the
      effects of the dynamical scattering on the contrast of bend contour crossings in
      conventional TEM images. In contrast to the CBED method, the bend contour method
      is performed in the image mode of the TEM. The sample can, therefore, be viewed
      while performing the polarity analysis. Furthermore, in the presence of strong
      foil bending, the bend contour method has some advantages for practical work. A
      general contrast rule for the bend contour intersections is stated which allows
      to readily obtain the crystal polarity by comparing the contrast in experimental
      images with the prediction of the rule. Exemplarily, the polarity of GaAs in TEM
      samples prepared for investigation in the two frequently used projections < 001 >
      and < 110 > is determined. The validity of the rule for the cases studied is
      confirmed by simulations of the dynamical scattering process. Furthermore, an
      independent analysis of the crystal polarity by making use of a long-range
      ordered (GaIn)P layer grown on top of the GaAs confirms the results obtained with
      the bend contour method. As an example, the usefulness of the method is
      demonstrated in an analysis of the alpha/beta-character of misfit dislocations at
      the interface between the GaAs substrate and the (GaIn)P layer.

PMID- 12213014
TI  - Conducting, semiconducting and insulating objects observed by low-energy electron
      holography.
AB  - To demonstrate the potential of low energy in line projection holography, we
      study the reconstruction of the experimental holograms of three electrically
      different objects: a conducting, a semiconducting and an insulating object. The
      reconstructions of these holograms provide meaningful results for a large range
      of magnification of the object. The comparison between the reconstructed images
      and the scanning electron microscopy (SEM) micrographs of the same objects shows
      that the shapes and the dimensions of the reconstructed objects are identical to
      those obtained by conventional SEM. So, the simple assumptions needed to the
      reconstruction are justified. The reconstructions show a 2 nm resolution and
      appear superior than the best obtained SEM micrographs, when available. We also
      show some limitations of the reconstruction process. We point out that both
      numerical artifacts and experimental conditions are responsible for these
      limitations.

PMID- 12213015
TI  - Detection of hydrogen by electron Rutherford backscattering.
AB  - A novel method for detection of hydrogen by an electron beam in extremely thin
      samples is described. Elastically scattered electrons impinging with 20-30 keV on
      a thin formvar film were detected at a scattering angle near 45 degrees. In these
      large momentum transfer elastic collisions a clear separation of the signal of
      hydrogen and heavier elements was found. By changing the momentum transfer we can
      verify that the hydrogen signal is not due to inelastic energy loss
      contributions. The width of the hydrogen elastic peak is much larger than the
      elastic peaks due to heavy elements (carbon and oxygen). The ratio of the
      hydrogen elastic peak and the main elastic peak is smaller than expected by 30
      50% depending on the energy of the impinging electron. This could be due to
      electronic excitations directly coupled to the elastic collision. The stability
      of the formvar film under electron radiation was studied. A reduction in
      thickness of the film with increasing fluence, as well as the preferential
      depletion of hydrogen, was found. Possible improvements of the experimental
      configuration for this type of experiments are discussed.

PMID- 12213016
TI  - Accuracy of AFM measurements of the contour length of DNA fragments adsorbed on
      mica in air and in aqueous buffer.
AB  - The measurement by atomic force microscope of the contour length of DNA fragments
      adsorbed on mica has been made as accurate as possible by revisiting the
      different steps of image acquisition and processing. In air, the DNA helical rise
      was estimated at 2.97 +/- 0.15 A per base pair (bp) (mean +/- standard deviation)
      by imaging a 648-bp DNA fragment and 2.95 +/- 0.14 A per bp for a 115-bp
      fragment. This confirms earlier observations suggesting that drying DNA fragments
      on mica in the presence of nickel induces limited conformational changes. At this
      point the exact nature of these conformational changes remains unknown. Simple
      hypotheses are the transconformation of stretches of the DNA molecules to the A
      form of the double helix or alteration of the helix structure at the points of
      contact between DNA and mica. By contrast, in aqueous buffer, the measured
      helical rise was 3.14 +/- 0.15 A per bp for the 648-bp fragment and 3.17 +/- 0.13
      A per bp for the 1115-bp fragment. Thus, measured helical rises do not depend on
      the fragment length and are significantly shorter than the 3.38 A per bp measured
      by crystallography, but close to the 3.18 A per bp found in NMR studies. These
      findings are discussed with respect to discrepancies in earlier results published
      in the literature.

PMID- 12213017
TI  - Preparation of thin ceramic monofilaments for characterization by TEM.
AB  - A method for preparing transmission electron microscopy specimens from ceramic
      fibers has been developed that is particularly useful when only a small amount of
      the material is available for characterization. Fiber segments are lined up and
      sandwiched between two glass slides using high-temperature epoxy. The resulting
      specimen is then polished flat from both sides using tripod polisher to remove
      the glass and produce thin (< 2 microm) longitudinal section of the fibers. The
      specimen is then ion-milled for a short time to produce electron-transparent
      areas. The method is also suitable for preparing very flat specimens for site
      specific optical and SEM analysis.

PMID- 12213018
TI  - A fast beam switch for controlling the intensity in electron energy loss
      spectrometry.
AB  - The fast deflection system described in this paper is suitable for controlling
      the intensity reaching the detector of a magnetic sector electron spectrometer
      mounted below an analytical transmission electron microscope. Amongst other
      things, this allows the low loss region of the spectrum to be recorded with the
      same electron probe conditions used to record core losses, something that is
      essential for high spatial resolution studies. The plate assembly restricts the
      width of the electron distribution reaching the viewing screen to a strip
      approximately 17 mm wide in the direction approximately normal to the dispersion
      direction of the spectrometer. The resulting deflection has no detectable effect
      on the FWHM of the zero-loss peak for exposure times as short as 1 micros. At
      incident energies up to 300 keV, positioning the deflection plates in the 35 mm
      camera port above the viewing chamber allows voltages of < +/- 3 kV to deflect
      the electrons out of the spectrometer and beyond the edge of the annular
      detector. When the deflection is switched on, the electrons are deflected out of
      the spectrometer in << 40 ns and when the deflection is switched off, the
      electrons return to within 10 microm of the undeflected position within 100 ns.
      Thus, even at an exposure time of 30 micros, the smallest time likely to be used
      in practice with a GATAN 666 spectrometer, < 1% of the signal in the spectrum is
      from electrons whose scattering conditions differ from those in the undeflected
      position. The performance of the deflection system is such that it will also be
      suitable for use with the new and much faster GATAN ENFINA spectrometer system.
      At incident energies up to 200 keV and possibly up to 300 keV, deflection
      voltages of +/- 3 kV are sufficient to deflect the electrons off a 1 k x 1 k
      charge coupled device (CCD) camera placed below the photographic camera. Thus the
      deflection system can be used as a very fast, non-mechanical shutter for such a
      CCD camera.

PMID- 12213019
TI  - Effect of small crystal tilt on atomic-resolution high-angle annular dark field
      STEM imaging.
AB  - Using a slightly tilted convergent electron beam, high-angle annular dark field
      scanning transmission electron microscopy observations have been performed of a
      [0 11]-oriented Si crystal. A small tilt of the crystal zone axis with respect to
      the coma-axis of the probe-forming lens causes a difference in intensity between
      bright spots of a Si dumbbell. The semiangle of the beam probe and the tilting
      angle with respect to the specimen hormal were determined by means of convergent
      beam micro-diffraction. The simulation using these parameters accounts for the
      image contrasts satisfactorily.

PMID- 12213020
TI  - Deconvolution processing of HAADF STEM images.
AB  - A deconvolution processing of high-resolution high-angle annular dark field
      (HAADF) scanning transmission electron microscopy (STEM) images, combined with
      maximum entropy method, is applied to two experimental [0 11]-Si images; one
      having unresolved dumbbells and the other having resolved dumbbells and
      artificial bright spots. The deconvoluted images for these images show bright
      spots corresponding to the projected atomic columns and no artificial bright
      spots. Thus, the deconvolution processing provides almost a real projected atomic
      structure by eliminating effects of the probe function from HAADF STEM images.

PMID- 12213021
TI  - A relocated technique of atomic force microscopy (AFM) samples and its
      application in molecular biology.
AB  - A kind of simple atomic force microscopy (AFM) relocated technique, which takes
      advantage of homemade sample locator system, is used for investigating repeatedly
      imaging of some specific species on the whole substrate (over 1 x 1 cm2) with
      resolution about 400 nm. As applications of this sample locator system, single
      extended DNA molecules and plasmid DNA network are shown in different AFM
      operational modes: tapping mode and contact mode with different tips after the
      substrates have been moved.

PMID- 12213022
TI  - Local lattice distortions in spherical carbon nanoparticles as studied by HRTEM
      image analysis.
AB  - The study of lattice distortions in structures with spherical or cylindrical
      geometry is of growing interest in the field of carbon nanoparticles (onions,
      nanotubes, etc.). We report an image analysis procedure entirely performed in
      reciprocal space which provides a global map of the inter-shell distances in
      carbon nanoparticles. This procedure is applied to carbon nanoparticles with a
      size of 100 nm that are generated under CVD conditions and exhibit positive as
      well as negative curvature of the basal lattice planes. These nanoparticles are
      subjected to intense electron irradiation under the beam of a high-voltage
      electron microscope with an acceleration voltage of 1.25 MeV. We observe a
      compression in their centre and a dilation of the outer shells. The reciprocal
      space analysis of the high-resolution electron microscopy images opens the way to
      investigate the stability and equilibrium structure of carbon nanoparticles and
      to conclude on the formation mechanism.

PMID- 12213023
TI  - Transfer-matrix simulations of field emission from a metallic (5,5) carbon
      nanotube.
AB  - We present three-dimensional simulations of field emission from an open (5,5)
      carbon nanotube without adsorption, by using a transfer-matrix methodology. By
      introducing pseudopotentials for the representation of carbon atoms and by
      repeating periodically a basic unit of the nanotube, band-structure effects are
      manifested in the distributions of energies. A representation of the band
      structure of the (5,5) nanotube is presented. The total-energy distributions of
      both the incident and field-emitted electrons contain peaks, which are related to
      discontinuities in the band structure or to standing waves in the carbon nanotube
      (a total length of 5.657 nm is considered). These peaks move to lower energies
      when the extraction field is increased. Such peaks should be observable in field
      emission experiments.

PMID- 12213024
TI  - Combined microscope for scanning X-ray transmission and surface topography.
AB  - A brief description is given of a scanning transmission X-ray microscope (STXM)
      for use with synchrotron radiation allowing simultaneous X-ray imaging and
      imaging of surface topography. Surface topography, appropriate to both conducting
      and non-conducting samples, is sensed by successive "specimen hopping" i.e.
      planting of the specimen at and withdrawal from a fixed sharp tip, or stylus,
      formed by the scanning tip of an atomic force microscope (AFM). First experiments
      are described with 3 keV photons with zone plate resolution of about 100 nm.
      Preliminary work is also mentioned to add a collimator to improve spatial
      resolution (in principle to < 20 nm for 300-500 eV photons), by installing a
      pierced AFM tip at the zone plate focus. The topographic measurement, currently
      with specimen thickness resolution of about 10 nm, but potential for
      approximately 1 nm, and feature-dependent in-specimen plane resolution of about
      100 nm as limited by the stylus geometry, is an adjunct to the STXM results, to
      provide information helpful in the interpretation of the X-ray image. Examples
      are given for simple specimens of the gains in specimen understanding from
      simultaneous STXM and hopping contact topographic images. Typical applications
      areas are radiation damage, and dynamic processes like specimen corrosion.

PMID- 12213025
TI  - High-resolution imaging with an aberration-corrected transmission electron
      microscope.
AB  - Recently an electromagnetic hexapole system for the correction of the spherical
      aberration of the objective lens of a 200 kV transmission electron microscope has
      been constructed by Haider and coworkers. By appropriately exciting the hexapole
      elements it is possible to adjust specific values of the spherical aberration
      coefficient ranging from the value of the original uncorrected instrument over
      zero even to negative values. In the first part of the paper the consequences of
      the tunable spherical aberration are investigated. New imaging modes are
      available: By adjustment of an optimum value for the spherical-aberration
      coefficient, the point resolution of phase-contrast imaging can be extended to
      the information limit. Phase-contrast imaging can be improved by a reduced level
      of contrast delocalisation. For zero aberration contrast delocalisation does not
      occur. In this case high-resolution investigations are carried out under
      amplitude-contrast conditions, where the local image intensity of crystalline
      objects is controlled by electron diffraction channelling. The defocus and
      spherical aberration values related to the new imaging modes are given. In the
      second part novel applications of the instrument to semiconductor
      heterostructures and ceramic grain boundaries are examined.

PMID- 12213026
TI  - Optical interference artifacts in contact atomic force microscopy images.
AB  - Atomic force microscopy images are usually affected by different kinds of
      artifacts due to either the microscope design and operation mode or external
      environmental factors. Optical interferences between the laser light reflected
      off the top of the cantilever and the light scattered by the surface in the same
      direction is one of the most frequent sources of height artifact in contact (and
      occasionally non-contact) images. They are present when imaging highly reflective
      surfaces, or even when imaging non-reflective materials deposited onto reflective
      ones. In this study interference patterns have been obtained with a highly
      polished stainless steel planchet. The influence of these artifacts in surface
      roughness measurements is discussed, and a semi-quantitative method based on the
      fast Fourier transform technique is proposed to remove the artifacts from the
      images. This method improves the results obtained by applying the usual
      flattening routines.

PMID- 12213027
TI  - Propagation of femtosecond light pulses through near-field optical aperture
      probes.
AB  - The propagation of femtosecond light pulses through near-field optical fiber tips
      has been modelled numerically in three spatial dimensions by means of the finite
      integration technique. Ideally conducting as well as real metallic coatings of
      the tip have been considered, and the influence of surface plasmon polaritons
      (SPP) on shape, spectrum, and amplitude of the light pulse in the near and far
      fields of the tip have been investigated in this way. Special attention has been
      devoted to the superluminal tunneling of light through the fiber tip. The
      variation of phase and group velocities along the fiber axis has been
      characterized for a number of real metals and for different tip angles. A maximum
      of both velocities in the near field of the tip is characteristic for coatings of
      finite conductivity. For some tip angles negative values of the phase and/or
      group velocities are observed, which are caused by the propagation of SPP on the
      outer surface of the coating and their conversion into photons. It is shown, that
      the excitation of SPP on the metallic coating leads to strongly altered spatial
      emission characteristics of the tip.

PMID- 12213028
TI  - Application of Nomarski interference contrast microscopy as a thickness monitor
      in the preparation of transparent, SiC-based, cross-sectional TEM samples.
AB  - Reflected light optical microscopy using a Nomarski prism and a differential
      interference contrast filter have been employed in concert to achieve a technique
      that provides an accurate color reference for thickness during the dimpling and
      ion milling of transparent transmission electron microscopy samples of 6H-SiC(000
      1) wafers. The samples had thin films of AIN, GaN, and Au deposited on the SiC
      substrate. A sequence of variously colored primary and secondary interference
      bands was observed when the SiC was thinner than 20 microm using an optical
      microscope. The color bands were correlated with the TEM sample thickness as
      measured via scanning electron microscopy. The interference contrast was used to
      provide an indication of the dimpling rate, the ion milling rate, and also the
      most probable location of perforation, which are useful to reduce sample
      breakage. The application of pressure during the initial cross-sectional
      preparation reduced the separation of the two halves of the sample sandwich and
      resulted in increased shielding of the film surface from ion milling damage.

PMID- 12213029
TI  - Polarity determination of III-V compound semiconductors by large-angle convergent
      beam electron diffraction.
AB  - The large-angle convergent beam electron diffraction (LACBED) technique is used
      for determining the crystal polarity of GaP and GaAs single crystals from < 1 1 0
      > cross-sectional samples. The method which is based on an earlier approach using
      convergent beam electron diffraction (CBED) evaluates the polarity-sensitive
      contrast of high odd-index Bragg-lines in [0 0 2] dark-field patterns. The
      polarity is determined by application of a simple contrast rule as well as by
      direct comparison with dynamical simulations. For the two materials the ranges of
      applicability are determined by a detailed analysis of the Bragg-line contrast as
      a function of the sample thickness. The coexistence of the Bragg-line pattern and
      the of shadow image of the defect in correct rotational relationship to each
      other makes the analysis straightforward and free from possible sources of
      errors. As an example, the crystal polarity of GaP is related to the morphology
      of facetted voids. The LACBED method is shown to be suitable for relating the
      analysis of extended crystal defects. The advantages and the disadvantages of the
      LACBED method are discussed in comparison with the corresponding CBED method and
      with a recent method based on the analysis of bend contours.

PMID- 12213030
TI  - Separation of pure elemental and oxygen influenced signal in ELNES.
AB  - The energy loss near edge structure (ELNES) of many elements is strongly
      influenced by the presence of oxygen or other elements at surfaces, grain
      boundaries, or in the bulk material. The presented investigation deals mainly
      with the influence of oxygen at the surface. A method for the separation of both,
      the pure bulk signal and the oxidized surface signal, was evaluated and tested on
      Al, Cu, Mg, and Si. A comparison of experimental data with ab initio
      bandstructure calculations and other proofs of the accuracy of ELNES separation
      are presented. Influences of error propagations were tested and are exemplarily
      given for Al and Si.

PMID- 12213031
TI  - Coherence and incoherence of inelastically scattered electron waves.
AB  - Whether the elastically and inelastically scattered electron waves are mutually
      coherent is a key question for the quantitative evaluation of the contrast of a
      high resolution transmission electron microscope image and for confirming the
      energy filtering ability of electron holography. Using a simplified object model
      composed of only two scattering centers the elastically and inelastically
      scattered electron waves and their detection are discussed. The only used proof
      for the main results of this paper is the orthogonality of the object states. The
      reasoning can be extended straightforward to a general case, e.g. a complicated
      object as well as complicated interaction Hamiltonians as long as they remain
      time independent. The results of this paper are: (1) The elastically and
      inelastically scattered waves which have different energy losses are mutually
      incoherent. The reason for that is simply that the corresponding excited object
      states are mutually orthogonal; (2) the inelastically scattered waves which have
      the same energy loss and are scattered by the same object state are coherent,
      whereas they are incoherent if they are scattered by different object states
      though they have the same energy; (3) the coherence degree of the scattered
      electron waves is proportional to the modulus of the scalar product of the
      corresponding object states.

PMID- 12213032
TI  - Nonclinical panic attacks in late adolescence prevalence and associated
      psychopathology.
AB  - This study investigated the prevalence of nonclinical panic attacks and
      associated psychopathology in 576 older adolescents. Nonclinical panic attacks
      are defined as panic occurring in individuals not seeking treatment. In this
      study, recent panickers (those reporting at least one nonclinical panic attack in
      the past month) comprised 12.2% of the sample. Nonpanickers and past panickers
      comprised 71.4 and 16.5% of the sample, respectively. Recent panickers evidenced
      significantly higher levels of trait anxiety, state anxiety, and depression, with
      a trend toward higher levels of anxiety sensitivity and internal negative
      attributions. This group also reported lower life experiences ratings suggesting
      higher levels of negative life stress. Finally, 46 recent panickers were
      administered a structured diagnostic interview, and 31 received a clinical
      diagnosis. The most common diagnoses were generalized anxiety disorder, social
      phobia, and specific phobia. Comorbidity rates were high in this sample: 24 of
      the 31 who received a diagnosis were comorbid with at least one other disorder.
      Implications of these findings for assessment and treatment are discussed.

PMID- 12213033
TI  - Two-year follow-up of self-examination therapy for generalized anxiety disorder.
AB  - This study examined the stability of treatment gains after receiving self
      examination therapy (SET) [Bowman, D. (1995). Innovations in clinical practice: a
      source book. Professional Resource Press.] for generalized anxiety disorder. A 2
      year follow-up of 16 participants from Bowman, Scogin, Floyd, Patton, and Gist
      [J. Counsel. Psychol. 44 (1997) 267] was conducted by comparing pre- and post
      treatment measures with follow-up measures from the Hamilton Anxiety Rating Scale
      Revised (HARS-R), the State-Trait Anxiety Inventory (STAI), and the SET quiz.
      Results indicated treatment gains from baseline to the 2-year follow-up period
      were maintained on all measures, and there was not a significant decline from
      post-treatment to follow-up on the HARS-R and STAI. These results suggest that
      SET for treatment of generalized anxiety disorder (GAD) may be effective in both
      the immediate and long-term reduction of GAD symptoms.

PMID- 12213034
TI  - Delimiting the boundaries of generalized anxiety disorder: differentiating high
      worriers with and without GAD.
AB  - Investigations of the boundary between generalized anxiety disorder (GAD) and
      normal worry have relied primarily on comparisons of GAD-diagnosed individuals
      with non-anxious controls. One limitation of this approach has been its inability
      to determine whether characteristics associated with GAD are unique to the
      disorder or are typical of severe worry more generally. The present studies made
      this differentiation using a virtually unstudied population: severe worriers
      failing to meet the diagnostic criteria for GAD. These studies assessed the
      prevalence of non-GAD high worriers in several college samples and identified
      features distinguishing them from individuals with GAD. Non-GAD high worriers far
      outnumbered GAD high worriers and reported many of the same symptoms as their GAD
      diagnosed counterparts. However, results revealed several characteristics that
      consistently distinguished the two groups. Implications for the
      conceptualization, assessment, and investigation of worry and GAD are discussed.

PMID- 12213035
TI  - Obsessions and compulsions and intolerance for uncertainty in a non-clinical
      sample.
AB  - It has been hypothesized that decision-making difficulties in patients with
      obsessive-compulsive disorder may arise from intolerance for uncertainty. We
      investigated the relationship between obsessivity and intolerance for uncertainty
      (defined in terms of need for cognitive closure), controlling for state and trait
      anxiety and depression. We tested nonclinical subjects through the Need for
      Closure Scale (NFCS), the Padua Inventory Revised (PI-R), the Beck Depression
      Inventory (BDI), and the State-Trait Anxiety Inventory (Form-Y; STAI-Y). A
      principal component analysis showed a lack of correlation between the PI-R and
      the NFCS subscales. A set of multiple regression analyses performed on PI-R
      subscales showed that the need for cognitive closure cannot be considered as a
      strong predictor of obsessions and compulsions. These results speak against the
      hypothesis that people with high obsessivity have difficulties in taking
      decisions because of a cognitive need for certainty. We instead argue that
      difficulties in taking decisions may be related to other specific cognitive
      beliefs or meta-beliefs.

PMID- 12213036
TI  - Comparison of clinical characteristics in good and poor insight obsessive
      compulsive disorder.
AB  - Beginning with DSM-III-R, the condition of an intact insight towards obsessive
      compulsive symptoms, which was essential for the classical definition of
      obsessivecompulsive neurosis, has been removed, permitting inclusion of cases
      with poor insight. A total of 94 cases who met DSM-III-R criteria for obsessive
      compulsive disorder were included in this study. The Structured Clinical
      Interview for DSM-III-R (SCID-P), YaleBrown Obsessive Compulsive Scale (Y-BOCS),
      Hamilton Rating Scale for Depression (HRSD), Hamilton Rating Scale for Anxiety
      (HRSA), and State-Trait Anxiety Inventory (STAI) were administered to each
      patient. Two subgroups determined by DSM-IV item "poor insight" were compared for
      demographic variables and the scores obtained on the scales. Scores on the Y
      BOCS, HRSA, HRSD and STAI-state were significantly higher in the poor insight
      group. Current and past major depression were also more frequent. Among
      personality disorders (PDs), avoidant PD was more common in the good insight
      group and borderline and narcissistic PDs were more common in the poor insight
      group. HRSA, HRSD, and STAI-state scores had weak to moderate but significant
      correlations with insight as defined by the item 11 of Y-BOCS. Findings are
      discussed in view of previous reports.

PMID- 12213037
TI  - The emotional Stroop: a comparison of panic disorder patients, obsessive
      compulsive patients, and normal controls, in two experiments.
AB  - An emotional Stroop task with four word types (panic threat, obsessive-compulsive
      threat, general threat, and neutral) and two presentation conditions
      (supraliminal, subliminal) was used in two experiments. The first experiment
      involved 21 panic disorder (PD) patients and 20 normal controls; the second
      experiment 20 PD patients and 20 obsessive-compulsive patients. PD patients,
      obsessive-compulsive patients, and normal controls did not differ in Stroop
      interferences. In addition, there were no significant correlations between
      reduction of PD symptoms and differences between pre- and post-treatment Stroop
      response latencies.

PMID- 12213038
TI  - Inflated perception of responsibility for harm in OCD patients with and without
      checking compulsions: a replication and extension.
AB  - In a follow-up study to [J. Anxiety Disord., in press] examination of inflated
      perception of responsibility for harm among individuals with obsessive compulsive
      disorder (OCs), 22 OC checkers, 24 OC non-checkers, and 25 non-anxious controls
      (NACs) completed the Obsessive Compulsive Responsibility Scale (OCRS), which
      consisted of written descriptions of Low-Risk (LR), Moderate-Risk (MR), and High
      Risk (HR) scenarios. In LR and MR scenarios, OC checkers reported greater
      perception of responsibility for harm and greater relief upon rectifying the
      situation, than did NACs. OC checkers also reported greater urges to rectify LR
      situations than did NACs. OC non-checkers did not differ from NACs on any of the
      scales. No group differences emerged for HR scenarios. The results suggest that,
      compared to OC non-checkers and to NACs, OC checkers have an inflated perception
      of responsibility for harm; and that this perception leads to a need to rectify
      potentially harmful situations.

PMID- 12213039
TI  - Anxiety sensitivity as a predictor of the development of panic symptoms, panic
      attacks, and panic disorder: a prospective study.
AB  - The purpose of the study was to examine how anxiety sensitivity (AS) acts as a
      dispositional factor in the development of panic symptoms, panic attacks, and
      panic disorder. Between 1986 and 1988, data were collected from 505
      undergraduates at an urban university. At Time 1, measures used were the ASI to
      assess AS, the trait scale of the State-Trait Anxiety Inventory (STAI-T) to
      measure trait anxiety, and self-report questionnaires to measure personal and
      family history of panic and anxiety symptoms. During the Spring of 1999, 178 of
      these subjects were re-contacted, and information was gathered on subjects'
      subsequent development of panic symptoms, panic attacks, panic disorder, and
      trait anxiety (STAI-T). The ASI was the strongest predictor of the development of
      panic symptoms and panic attacks. After controlling for trait anxiety, the ASI
      was not predictive of the development of panic disorder.

PMID- 12213040
TI  - Does witnessing experimental procedures produce stress in male rats?
AB  - The objective of this study was to test the hypotheses that male rats are
      stressed by being in the same room as animals subjected to common husbandry and
      experimental procedures and that the level of stress is affected by housing
      density. Two commonly used indices of stress, heart rate (HR) and mean arterial
      blood pressure (MAP), were determined by using radiotelemetry for 2 h before and
      3 h after rats witnessed the following procedures: decapitation, decapitation and
      necropsy, cage change, restraint and subcutaneous injection, and restraint and
      tail-vein injection. In addition, home cage behaviors (sleeping, awake, moving,
      rearing, and grooming) were scored once each minute for 15 min before and 45 min
      after the procedures. Witnessing decapitation or decapitation and necropsy of 6
      other rats induced small, but significant, increases in HR and MAP in animals
      housed alone, whereas responses in animals housed with one or three cagemates
      were more transient or not significant. Witnessing a routine cage change also
      induced small increases in HR and MAP in rats housed alone or with one cagemate,
      but HR and MAP decreased in rats housed four per cage. HR and MAP did not change
      in rats witnessing restraint and a subcutaneous injection of other rats, but
      these indices were transiently increased when rats witnessed animals being
      restrained in a rodent restrainer and given a tail-vein injection. Home cage
      behaviors were significantly altered only in rats witnessing decapitation and
      necropsy and then only in rats housed alone. We conclude that male Sprague-Dawley
      rats are not significantly stressed when present in the same room in which
      decapitation or other common experimental procedures are being performed,
      especially when the animals are housed with cagemates.

PMID- 12213041
TI  - Short-term effects of an environmental enrichment program for adult cynomolgus
      monkeys.
AB  - Behavior patterns (including behavior disorders) of cynomolgus monkeys are
      established early in life, and exploratory behavior lessens with age. Whether
      environmental enrichment programs benefit these animals can be questioned,
      particularly for animals housed short-term. We evaluated the overall effect of
      our environmental enrichment program in 40 newly arrived male and female adult
      cynomolgus monkeys to determine whether it impacted animal well-being. Animals
      allocated into two groups one that received environmental enrichment (the 
      enriched  group) and one that did not (the  nonenriched,  control group) and
      behaviors were assessed over a 5-week period. We also examined the effect of
      enrichment on training time for a simple activity (entering a transfer box).
      Animals that had environmental enrichment made use of additional cage space,
      toys, and foraging items, but trends in observed in-cage behavior patterns were
      relatively unchanged throughout the course of the study. After study completion,
      physical evidence of self-trauma was found in 25% of the nonenriched animals but
      not in any of those in the enriched group. Enrichment had no notable effect on
      body weight or training time for a simple activity. Our findings suggest that
      provision of a comprehensive environmental enrichment program provides a
      beneficial effect to adult cynomolgus macaques singly housed short-term.

PMID- 12213042
TI  - Methods for predicting sexual maturity in male cynomolgus macaques on the basis
      of age, body weight, and histologic evaluation of the testes.
AB  - In pharmaceutical drug safety testing, sexual maturity is an important
      experimental parameter. Histologic immaturity of the tissues of the reproductive
      system can interfere with the interpretation of compound-related effects on the
      reproductive organs. In female cynomolgus macaques, determination of sexual
      maturity is simplified by the presence of a menstrual cycle. For male cynomolgus
      macaques, predicting maturity is much more difficult. In this study, we evaluated
      methods that would reliably predict sexual maturity in male cynomolgus macaques.
      The results of histologic examination of testes of control male cynomolgus
      macaques used for drug safety studies were examined retrospectively for evidence
      of sexual maturity. These data were compared with age and body weight
      determinations to establish statistical models for determining the probability
      that a male cynomolgus macaque is sexually mature. This model presents a simple
      prospective method of predicting sexual maturity in male cynomolgus macaques.

PMID- 12213043
TI  - Review of growth plate closure compared with age at sexual maturity and lifespan
      in laboratory animals.
AB  - Although it is assumed that most mammals experience growth plate closure and
      cessation of bone growth soon after sexual maturity, bone growth in rats
      continues throughout their lifespan. The rat was compared to other laboratory
      animals to assess differences in the duration of bone growth and its relationship
      to age at sexual maturity and lifespan. We reviewed the literature from 1966 to
      March 1999 by searching MEDLINE and other databases. Growth closure times and age
      at sexual maturity were retrieved for the mouse, rabbit, dog, cat, sheep, cow,
      horse, nonhuman primates, and human. For all species, we calculated the ratios
      of: 1) age at growth plate closure to lifespan, 2) age at growth plate closure to
      age at sexual maturity, and 3) age at sexual maturity to average lifespan. The
      ratio of age at physis closure to the average lifespan was large for the rat (22
      to 35) and showed some overlap with that of humans (17 to 25); this ratio was
      comparatively small in all other nonhuman species (range, 4 to 17). This finding
      indicates that bone growth continues in the rat for a greater proportion of their
      lifespan than does that in other species. The ratio of age at physis closure to
      age at sexual maturity was larger for the rat (5 to 6) than that for other
      species, indicating that bone growth continues much longer after sexual maturity
      in rats than in other animals. The ratio of age at sexual maturity to average
      lifespan was largest for humans and nonhuman primates (13 to 14), indicating the
      increased time to reach puberty versus that in other species. These differences
      are important for studies in which animal models are used in research involving
      bone growth.

PMID- 12213044
TI  - Age- and gender-related changes in copper and zinc levels in the plasma of
      Mongolian gerbils.
AB  - Zinc and copper are components of many enzymes. Little information exists on the
      levels of trace elements in the plasma of the Mongolian gerbil (Meriones
      unguiculatus). We studied the age- and gender-related differences in the plasma
      Zn and Cu levels of healthy Mongolian gerbils. The 30 male and 30 female animals
      were allocated into three age groups (group A, 90 days old; group B, 180 days
      old; and group C, 360 days old), with 10 animals of each gender per group. They
      were housed under standard conditions with free access to pelleted rodent
      maintenance diet (Zn, 95 mg/kg; Cu, 30 mg/kg) and water (Zn, undetectable; Cu, <
      0.45 mg/liter). Overall, plasma Cu levels (mean   1 standard deviation) were
      significantly higher in female (2.03   0.41 mg/ml) than male (1.30   0.28 mg/ml;
      P < 0.0001) gerbils. Among the male rodents, those in group B had the lowest Cu
      levels, whereas among the females, the lowest values were in group A. In
      contrast, plasma Zn levels did not differ between genders (males, 2.96   0.43
      mg/ml; females, 2.96   0.38 mg/ml) or age groups. In general, plasma Cu and Zn
      levels were higher in gerbils than rats. We conclude that gerbils may be an
      interesting model for studying the metabolism of these trace elements.

PMID- 12213045
TI  - Cerebrospinal fluid centesis at the cerebellomedullary cistern of kittens.
AB  - We needed an effective technique for obtaining cerebrospinal fluid (CSF) from
      young (2- to 18-week-old) kittens. Standard veterinary technique was not
      suitable, so we adapted a previously published technique for rats. We first
      established an effective isoflurane-only anesthetic protocol for young kittens.
      After inhalant anesthesia, the kittens were positioned on a supporting platform
      to gain flexion of the head and neck. A micromanipulator was used to hold and
      slowly advance the collection needle. At the time this report was written, we had
      collected a total of 33 samples from eight kittens without causing apparent
      neurologic deficits. Correct positioning of the animal and collection needle was
      critical for success. This procedure enabled the collection of approximately 0.5
      ml CSF from kittens younger than 12 weeks and larger volumes from older kittens.

PMID- 12213046
TI  - Pathology of a mouse model of x-linked chronic granulomatous disease.
AB  - A colony of knockout mice (gene designation Cybb tm1) has been maintained at this
      institution for 5 years. These mice are lacking the b subunit of NADPH oxidase
      and are susceptible to experimental infection with Aspergillus fumigatus. The
      purpose of this study was to document the spontaneous diseases present in these
      mice which are a murine model of X-linked chronic granulomatous disease and to
      compare these lesions to those of chronic granulomatous disease in humans.
      Lesions were documented in 72 mice submitted to the necropsy service. All 72 mice
      had an acidophilic macrophage pneumonia, and 16 also had lobar suppurative and
      necrotizing pneumonias caused by Paecilomyces sp. (11 of the 16 mice), A.
      fumigatus (3 mice), Rhizopus sp. (1 mouse), or Candida guilliermondii (1 mouse).
      Of the 72 animals, 36 had severe bacterial suppurative and necrotizing to
      pyogranulomatous pneumonias; lung abscesses yielded cultures of Pseudomonas
      aeruginosa (n = 3), Enterococcus (n = 6), Staphylococcus aureus (n = 2), S.
      xylosus (n = 1), coagulase-negative Staphylococcus sp. (n = 4), gram-negative
      enteric bacilli (n = 6), Klebsiella pneumoniae (n = 1), and Proteus mirabilis (n
      = 2). Thirteen mice had a necrotizing and suppurative adenitis of the cervical
      lymph nodes caused by coagulase-negative Staphylococcus sp.; S. aureus, S.
      xylosus, and S. equorum were recovered from abscesses in the cervical lymph
      nodes, extremities, and head. Splenomegaly was found in 30 animals and
      lymphadenopathy in 11 mice. The array of spontaneously occurring infectious
      diseases and lesions in these mice is similar to that of human patients with
      chronic granulomatous disease.

PMID- 12213047
TI  - Multiple congenital genitourinary anomalies in a polled goat.
AB  - A 1-day-old, Toggenburg/Nubian crossbred goat of polled parentage was referred
      for necropsy because of a large (diameter, 5 cm) bladder-like mass protruding
      from the perineal midline and difficult urination. Differential diagnoses
      included cutaneous cyst, ectopic urinary bladder, and urethral
      diverticulum/dilatation. Several genitourinary aberrations were noted. A second,
      smaller (diameter, 1 cm), more distal cystic structure was adjacent to an
      ambiguous prepuce. Testicles were discovered within a constricted, subcutaneous
      space near the inguinal canals. A rudimentary penis was located dorsal to the
      penile urethra with no appreciable urethral process. A tiny external urethral
      orifice was discerned only after liquid was injected into the lumen of the cystic
      structures, confirming their identity as urethral dilatations. The dilatations
      were separated by a constricting band of fibrous tissue. No other significant
      findings were detected. This case illustrates a combination of congenital
      anomalies including bilateral cryptorchidism with scrotal absence, segmental
      urethral hypoplasia, and urethral dilatation, most likely associated with the
      intersex condition seen in polled breeds. The continued production and use of
      small ruminants as animal models demands the prompt recognition of congenital
      anomalies. This case also exemplifies the precautions required when breeding
      goats with polled ancestry.

PMID- 12213048
TI  - Virucidal effects of rodent cage-cleaning practices on the viability of
      adenovirus vectors.
AB  - Human adenoviruses and adenoviral vectors are classified as Risk Group 2 agents
      and require BSL2 containment and practices. An additional consideration in using
      adenoviruses and viral vectors in laboratory animal studies is the possible
      transmission of these agents to other animals and/or personnel as a result of
      viral shedding in animal urine and feces. When handling BSL2 agents, cage-wash
      staff are required to wear appropriate personnel protective equipment, including
      scrubs, Tyvek suit, hair covering, dust mask, shoes covers, and gloves. Current
      decontamination procedures are to bag and autoclave soiled rodent cages
      containing bedding prior to washing in the cage washer to prevent possible
      adenoviral transmission. However, the practice of autoclaving softens the
      polycarbonate-based rodent cages, allowing damaging agents or conditions to
      affect the integrity of the plastic and degrade the cages. The objective of this
      study was to determine whether current rodent cage-cleaning practices produced
      virucidal effects for use in lieu of or prior to autoclaving the cages. We found
      that heating an Av3GFP vector in a test tube to a temperature of 74 degrees C
      (165 degrees F) for 6 min conditions equivalent to those of the cage washer
      resulted in greater than an 11-log reduction in infectivity of the vector as
      evaluated by its cytopathic effect on cells. The combination of heating and a
      liquid, phosphate-free alkaline detergent produced the same reduction in vector
      infectivity. However, common cage-cleaning solutions alone possessed no virucidal
      activity. The high temperatures used in cage-washing procedures alone or in
      combination with a cleaning solution reduced or eliminated the risk of
      transmission from viral shedding through urine and feces even at vector
      concentrations far greater than would ever be expected to be present. Autoclaving
      cages diminishes the stability and integrity of the polycarbonate cages without
      providing a further reduction in the risk of virus or vector transmission. On the
      basis of results from this study, new cage-wash recommendations include dumping
      the contaminated bedding into a HEPA-filtered waste disposal system and
      autoclaving the bags of bedding before disposal, then cleaning the cages in the
      rack washer at wash temperatures of 74 degrees C (165 F) and rinse temperatures
      of 82 degrees C (180 F).

PMID- 12213049
TI  - Nonhuman primate cage modifications for environmental enrichment.
AB  - Both to meet the regulatory requirements of the Animal Welfare Act and the
      increasing body of evidence supporting that most species of nonhuman primates
      (NHP) should be group-housed whenever possible, modifications to nonhuman primate
      caging are described. Perches and cage-connecting tunnels were fabricated for
      existing macaque caging. These are semi-permanent, easily sanitizable, and allow
      for all cage functions to operate as designed. All NHP housed in these cages were
      part of experimental studies approved by the institutional animal care and use
      committee.

PMID- 12213050
TI  - Flow cytometry.

PMID- 12213051
TI  - Purine and pyrimidine (P2) receptors as drug targets.

PMID- 12213052
TI  - Pyrimidinylpyrroloquinolones as highly potent and selective PDE5 inhibitors for
      treatment of erectile dysfunction.
AB  - A series of N-pyrimidinylpyrroloquinolones were discovered as extremely potent
      and selective PDE5 inhibitors. Representative compounds demonstrated in vivo
      efficacy in dog erectile dysfunction models and are orally bioavailable.

PMID- 12213053
TI  - Mazindol analogues as potential inhibitors of the cocaine binding site at the
      dopamine transporter.
AB  - A series of mazindol (2) and homomazindol (3) analogues with a variety of
      electron-donating and electron-withdrawing groups in the pendant aryl group and
      the benzo ring C, as well as H, methoxy, and alkyl groups replacing the hydroxyl
      group were synthesized, and their binding affinities at the dopamine transporter
      (DAT) on rat or guinea pig striatal membranes were determined. Several active
      analogues were also evaluated for their ability to block uptake of DA, 5-HT, and
      NE and inhibit binding of [(125)I] RTI-55 at HEK-hDAT, HEK-hSERT, and HEK-hNET
      cells. Mazindane (26) was found to be a pro-drug, oxidizing (5-H --> 5-OH) to
      mazindol on rat striatal membranes and HEK-hDAT cells. The 4',7,8-trichloro
      analogue (38) of mazindol was the most potent and selective ligand for HEK-hDAT
      cells (DAT K(i) = 1.1 nM; SERT/DAT = 1283 and NET/DAT = 38). Experimental results
      strongly favor the cyclic or ol tautomers of 2 and 3 to bind more tightly at the
      DAT than the corresponding keto tautomers.

PMID- 12213054
TI  - Benzo- and cyclohexanomazindol analogues as potential inhibitors of the cocaine
      binding site at the dopamine transporter.
AB  - A series of mazindol (1), homomazindol (2), and bishomomazindol (3) derivatives
      with a benzo or cyclohexano ring fused at various sites were prepared as part of
      an SAR study to determine the effect of increased aliphatic and aromatic
      lipophilicity on selected in vitro assays used to identify potential cocaine-like
      and cocaine antagonism activity. Very good (IC(50) = 2-3 nM) inhibition of [(3)H]
      WIN 35,428 and [(125)I] RTI-55 binding on rat or guinea pig striatal membranes
      and HEK cells expressing cDNA for the human dopamine transporter (HEK-hDAT) was
      shown by the 8,9-benzomazindol 25 and 9,10-benzohomomazindol 28. All new
      compounds were weaker inhibitors of [(3)H] DA uptake in HEK-hDAT cells than 1 and
      2. No improvement in the binding selectivity ratio (SERT/DAT and NET/DAT) was
      found when compared to 2. Compounds 25and 28 showed a considerable increase
      versus 1 in uptake/binding discrimination ratios at the DAT (311.0 and 182.1 vs
      0.9), SERT (33.6 and 127.3 vs 1.9), and NET (7.3 and 10.0 vs 0.3).

PMID- 12213055
TI  - Three-dimensional quantitative structure-activity relationships of mazindol
      analogues at the dopamine transporter.
AB  - A three-dimensional quantitative structure-activity relationship (3D-QSAR) study
      was performed on a series of mazindol analogues using the comparative molecular
      field analysis (CoMFA) method with their corresponding binding affinities for the
      displacement of [(3)H]WIN 35 428 from rat caudate putamen tissue. The cross
      validated CoMFA models were derived from a training set of 50 compounds, and the
      predictive ability of the resulting CoMFA models was evaluated against a test set
      of 21 compounds. A set of alignment rules was derived to superimpose these
      compounds onto a template structure, mazindol (1). These CoMFA models yielded
      significant cross-validated r(2)(cv) values. Inclusion of additional descriptors
      did not improve the significance of the CoMFA models; thus, steric and
      electrostatic fields are the relevant descriptors for these compounds. The best
      QSAR model was selected on the basis of the predictive ability of the activity on
      the external test set of compounds. The analysis of coefficient contour maps
      provided further insight into the binding interactions of mazindol analogues with
      the DAT. The aromatic rings C and D are involved in hydrophobic interactions in
      which ring D may bind in a large hydrophobic groove. The relative orientation of
      these two rings is also important for high binding affinity to the DAT.

PMID- 12213057
TI  - Molecular modeling of the interactions of glutamate carboxypeptidase II with its
      potent NAAG-based inhibitors.
AB  - Glutamate carboxypeptidase II (GCPII, NAALADase, or NAAG peptidase) is a
      catalytic zinc metallopeptidase. Its extracellular domain hydrolyzes the abundant
      neuropeptide, N-acetyl-L-aspartyl-L-glutamate (NAAG), to produce N
      acetylaspartate and glutamate following the synaptic release of this transmitter.
      Thus, GCPII influences the extracellular concentrations of both glutamate and
      NAAG. NAAG activates group II metabotropic glutamate receptors, and activation of
      this receptor has been found to protect against anoxia-induced excitotoxic nerve
      cell death. In contrast, high levels of glutamate can be neurotoxic. Thus, GCPII
      is a potential therapeutic target for the reduction of excitotoxic levels of
      glutamate and enhancement of extracellular NAAG. To explore the structural basis
      of the interaction between GCPII and its inhibitors, we modeled the three
      dimensional structure of the GCPII extracellular domain using a homology modeling
      approach. On the basis of the GCPII model, the structures of GCPII in complex
      with its potent inhibitors 2-(phosphonomethyl)pentanedioic acid (PMPA) and 4,4'
      phosphinicobis(butane-1,3-dicarboxylic acid) (PBDA) were built by a computational
      docking method. The model of GCPII mainly consists of two alpha/beta/alpha
      sandwiches, between which two zinc ions are quadrivalently coordinated by the
      His379-Asp389-Asp455-H(2)O and the Asp389-Glu427-His555-H(2)O clusters,
      respectively. The ligand binding pocket is situated between these two sandwiches
      and is comprised of two subpockets: one is a surface-exposed highly positively
      charged subpocket; the other is a buried hydrophobic subpocket. The positively
      charged subpocket can accommodate the pharmacophore groups of inhibitor molecules
      (PMPA and PBDA) through the coordination of Zn(2+) with their phosphorus
      functionality and hydrogen-bonding interactions with Arg536, Arg538, and Ser456
      (or Asn521), while the hydrophobic subpocket is engaged in hydrophobic and
      hydrogen-bonding interactions with the nonpharmacophore groups of PBDA. The
      predicted binding mode is consistent with the experimental data obtained from
      site-directed mutagenesis. On the basis of the predicted interaction mode, our
      structure-based design has led to a series of highly potent GCPII inhibitors.

PMID- 12213056
TI  - Synthesis and molecular modeling of new 1-aryl-3-[4-arylpiperazin-1-yl]-1-propane
      derivatives with high affinity at the serotonin transporter and at 5-HT(1A)
      receptors.
AB  - It has been proposed that 5-HT(1A) receptor antagonists augment the
      antidepressant efficacy of selective serotonin (5-HT) reuptake inhibitors. In a
      search toward new and efficient antidepressants, 1-(aryl)-3-[4-arylpiperazin-1
      yl]-1-propane molecular hybrids were designed, synthesized, and evaluated for 5
      HT reuptake inhibition and 5-HT(1A) receptor affinity. The design was based in
      coupling structural moieties related to inhibition of serotonin reuptake, such as
      benzo[b]thiophene derivatives to arylpiperazines, typical 5-HT(1A) receptor
      ligands. In binding studies, several compounds showed affinity at the 5-HT
      transporter and at 5-HT(1A) receptors. Molecular modeling studies predicted the
      pharmacophore elements required for high affinity binding and the features that
      enable to discriminate between agonist, partial agonist, or antagonist action at
      5-HT(1A) receptors and 5-HT transporter inhibition. Solvent interactions in
      desolvation prior to the binding step along with enthalpy and enthropy
      compensations might be responsible to explain agonist, partial agonist, and
      antagonist character. Hydrogen-bonding capability seems to be important to break
      hydrogen interhelical hydrogen bonds or alternatively to form other bonds upon
      ligand binding. Partial agonists and antagonists are unable to do this as the
      full agonist, which interacts closely by long-range forces or directly. The
      compounds showing the higher affinity at both the 5-HT transporter (K(i) < 50 nM)
      and the 5-HT(1A) receptors (K(i) < 20 nM) were further explored for their ability
      to stimulate [(35)S]GTPgammaS binding or to antagonize 8-hydroxy-2-di-n
      propylamino-tetralin (8-OH-DPAT)-stimulated [(35)]GTPgammaS binding to rat
      hippocampal membranes, an index of agonist/antagonist action at 5-HT(1A)
      receptors, respectively. Compound 8g exhibited agonist activity (EC(50) = 30 nM)
      in this assay, whereas compounds 7g and 8h,i behaved as weak partial agonists and
      7h-j and 8j,l antagonized the R(+)-8-OH-DPAT-stimulated GTPgammaS binding.
      Functional characterization was performed by measuring the antagonism to 8-OH
      DPAT-induced hypothermia in mice.

PMID- 12213058
TI  - DrugScore meets CoMFA: adaptation of fields for molecular comparison (AFMoC) or
      how to tailor knowledge-based pair-potentials to a particular protein.
AB  - The development of a new tailor-made scoring function to predict binding
      affinities of protein-ligand complexes is described. Knowledge-based pair
      potentials are specifically adapted to a particular protein by considering
      additional ligand-based information. The formalism applied to derive the new
      function is similar to the well-known CoMFA approach, however, the fields used in
      the approach originate from the protein environment (and not from the aligned
      ligands as in CoMFA, thus, a "reverse" CoMFA (= AFMoC) named Adaptation of Fields
      for Molecular Comparison is performed). A regular-spaced grid is placed into the
      binding site and knowledge-based pair-potentials between protein atoms and ligand
      atom probes are mapped onto the grid intersections resulting in "potential
      fields". By multiplying distance-dependent atom-type properties of actual ligands
      docked into the binding site with the neighboring grid values, "interaction
      fields" are produced from the original "potential fields". In a PLS analysis,
      these atom-type specific interaction fields are correlated to the actual binding
      affinities of the embedded ligands, resulting in individual weighting factors for
      each field value. As in CoMFA, the results of the analysis can be interpreted in
      graphical terms by contribution maps, and binding affinities of novel ligands are
      predicted by applying the derived 3D QSAR equation. The scope of the new method
      is demonstrated using thermolysin and glycogen phosphorylase b as test examples.
      Impressive improvements of the predictive power for affinity prediction can be
      achieved compared to the application of the original knowledge-based potentials
      by considering a sample set of only 15 known training ligands. Thus, with growing
      information about the drug target studied, the new method allows one to move
      gradually from generally valid to protein-specifically adapted pair-potentials,
      depending on the amount of training information available and its degree of
      structural diversity. In addition, convincing predictive power is also achieved
      for ligand poses generated by automatic docking tools.

PMID- 12213059
TI  - 6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide derivatives
      potently and selectively activate ATP sensitive potassium channels of pancreatic
      beta-cells.
AB  - 6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide derivatives
      were synthesized and characterized as activators of adenosine 5'-triphosphate
      (ATP) sensitive potassium (K(ATP)) channels in the beta-cells by measuring
      effects on membrane potential and insulin release in vitro. The effects on
      vascular tissue in vitro were measured on rat aorta and small mesenteric vessels.
      Selected compounds were characterized as competitive inhibitors of
      [(3)H]glibenclamide binding to membranes of HEK293 cells expressing human
      SUR1/Kir6.2 and as potent inhibitors of insulin release in isolated rat islets. 6
      Chloro-3-(1-methylcyclobutyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide
      (54) was found to bind and activate the SUR1/Kir6.2 K(ATP) channels in the low
      nanomolar range and to be at least 1000 times more potent than the reference
      compound diazoxide with respect to inhibition of insulin release from rat islets.
      Several compounds, e.g., 3-propylamino- (30), 3-isopropylamino- (34), 3-(S)-sec
      butylamino- (37), and 3-(1-methylcyclopropyl)amino-4H-thieno[3,2-e]-1,2,4
      thiadiazine 1,1-dioxide (53), which were found to be potent and beta-cell
      selective activators of K(ATP) channels in vitro, were found to inhibit insulin
      secretion in rats with minimal effects on blood pressure and to exhibit good oral
      pharmacokinetic properties.

PMID- 12213060
TI  - Refinement and evaluation of a pharmacophore model for flavone derivatives
      binding to the benzodiazepine site of the GABA(A) receptor.
AB  - To further develop and evaluate a pharmacophore model previously proposed by Cook
      and co-workers (Drug Des. Discovery 1995, 12, 193-248) for ligands binding to the
      benzodiazepine site of the GABA(A) receptor, 40 new flavone derivatives have been
      synthesized and their affinities for the benzodiazepine site have been
      determined. Two new regions of steric repulsive interactions between ligand and
      receptor have been characterized, and the receptor region in the vicinity of 6-
      and 3'-substituents has been mapped out. 2'-Hydroxy substitution is shown to give
      a significant increase in affinity, which is interpreted in terms of a novel
      hydrogen bond interaction with the previously proposed hydrogen bond-accepting
      site A2. On the basis of the results of these studies and the refined
      pharmacophore model, 5'-bromo-2'-hydroxy-6-methylflavone, the highest affinity
      flavone derivative reported so far (K(i) = 0.9 nM), was successfully designed. A
      comparison of the pharmacophore model with a recently proposed alternative model
      (Marder; et al. Bioorg. Med. Chem., 2001, 9, 323-335) has been made.

PMID- 12213061
TI  - Azapeptides structurally based upon inhibitory sites of cystatins as potent and
      selective inhibitors of cysteine proteases.
AB  - A series of azapeptides as potential inhibitors of cysteine proteases were
      synthesized. Their structures, based on the binding center of cystatins, contain
      an azaglycine residue (Agly) in place of the evolutionarily conserved glycine
      residue in the N-terminal part of the enzyme binding region of cystatins.
      Incorporation of Agly should lead to deactivation of the acyl-enzyme complex
      formed against nucleophilic attack by water molecules in the final step of
      peptide bond hydrolysis. The majority of synthesized azapeptides shows high
      inhibitory potency toward the investigated cysteine proteases, papain, cathepsin
      B, and cathepsin K. One of them, Z-Arg-Leu-Val-Agly-Ile-Val-OMe (compound 17),
      which contains in its sequence the amino acid residues from the N-terminal
      binding segment as well as the hydrophobic residues from the first binding loop
      of human cystatin C, proved to be a highly potent and selective inhibitor of
      cathepsin B. It inhibits cathepsin B with a K(i) value of 0.088 nM. To
      investigate the influence of the structure of compound 17 for its inhibitory
      properties, we determined its conformation by means of NMR studies and
      theoretical calculations. The Z-Arg-Leu-Val-Agly fragment, covalently linked to
      Cys29 of cathepsin B, was also developed and modeled, in the catalytic pocket of
      the enzyme, through a molecular dynamics approach, to analyze ligand-protein
      interactions in detail. Analysis of the simulation trajectories generated using
      the AMBER force field provided us with atomic-level understanding of the
      conformational variability of this inhibitor, which is discussed in the context
      of other experimental and theoretical data.

PMID- 12213062
TI  - Synthesis of a novel series of benzocycloalkene derivatives as melatonin receptor
      agonists.
AB  - We synthesized a novel series of benzocycloalkene derivatives and evaluated their
      binding affinities to melatonin receptors. To control the spatial position of the
      amide group, one of the important pharmacophores, we incorporated an endo double
      bond, an exo double bond (E- and Z-configurations), and a chiral center (R- and S
      configurations) at position 1. The indan derivatives with the S-configuration at
      position 1 were the most promising in terms of potency and selectivity for the
      human melatonin receptor (MT(1) site), while compounds with the R-configuration
      showed little potential. Our next attempt was to investigate the most favorable
      conformation of the methoxy group, the other important pharmacophore for binding
      to the MT(1) receptor. The introduction of a methyl group at position 5 of the
      indene ring conserved affinity; however, at position 7, it caused a decrease in
      affinity. These results suggested that the substitution at position 7 forced the
      methoxy group to adopt an unfavorable orientation. The optimization of the
      condensed ring size and substituents led to (S)-8d [(S)-N-[2-(2,3-dihydro-6
      methoxy-1H-inden-1-yl)ethyl]propionamide], which had high affinity for the human
      MT(1) receptor (K(i) = 0.041 nM) but no significant affinity for the hamster
      MT(3)receptor (K(i) = 3570 nM). In addition, a practical synthetic method of
      chiral N-[2-(2,3-dihydro-1H-inden-1-yl)ethyl]alkanamides employing asymmetric
      hydrogenation with (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl-Ru has been
      established.

PMID- 12213063
TI  - Synthesis of a novel series of tricyclic indan derivatives as melatonin receptor
      agonists.
AB  - To develop a new therapeutic agent for sleep disorders, we synthesized a novel
      series of tricyclic indan derivatives and evaluated them for their binding
      affinity to melatonin receptors. In our previous paper, we proposed a
      conformation of the methoxy group favorable for the binding of the MT(1)
      receptor. To fix the methoxy group in an active conformation, we decided to
      synthesize conformationally restricted tricyclic indan analogues with the oxygen
      atom in the 6-position incorporated into a furan, 1,3-dioxane, oxazole, pyran,
      morpholine, or 1,4-dioxane ring system. Among these compounds, indeno[5,4-b]furan
      analogues were found to be the most potent and selective MT(1) receptor ligands
      and to have superior metabolic stability. The optimization of substituents led to
      (S)-(-)-22b, which showed very strong affinity for human MT(1) (K(i) = 0.014 nM),
      but no significant affinity for hamster MT(3)() (K(i) = 2600 nM) or other
      neurotransmitter receptors. The pharmacological effects of (S)-(-)-22b were
      studied in experimental animals, and it was found that a dose of 0.1 mg/kg, po
      promoted a sleep in freely moving cats, as demonstrated by a decrease in
      wakefulness and increases in slow wave sleep and rapid eye movement sleep, which
      lasted for 6 h after administration. Melatonin (1 mg/kg, po) also had a sleep
      promoting effect, though it lasted only 2 h. A new chiral method for the
      synthesis of (S)-(-)-22b starting from 60, which was prepared from 59 employing
      asymmetric hydrogenation with the (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl
      Ru complex, was developed. (S)-(-)-22b (TAK-375) is currently under clinical
      trial for the treatment of insomnia and circadian rhythm disorders.

PMID- 12213064
TI  - Selective agonists at group II metabotropic glutamate receptors: synthesis,
      stereochemistry, and molecular pharmacology of (S)- and (R)-2-amino-4-(4
      hydroxy[1,2,5]thiadiazol-3-yl)butyric acid.
AB  - Homologation of analogues of the central excitatory neurotransmitter glutamic
      acid (Glu), in which the distal carboxy group has been bioisosterically replaced
      by acidic heterocyclic units, has previously provided subtype selective ligands
      for metabotropic Glu receptors (mGluRs). The (S)-form of the 1,2,5-thiadiazol-3
      ol Glu analogue, 2-amino-3-(4-hydroxy[1,2,5]thiadiazol-3-yl)propionic acid (TDPA,
      6), is an 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA)
      receptor agonist, which in addition stereospecifically activates group I mGluRs.
      We have now synthesized the (S)- and (R)-forms of 2-amino-4-(4
      hydroxy[1,2,5]thiadiazol-3-yl)butyric acid (homo-TDPA, 7) and shown that whereas
      neither enantiomer interacts with AMPA receptors, (S)- and (R)-7 appear to be
      selective and equipotent agonists at group II mGluRs as represented by the mGluR2
      subtype. The activities of (S)- and (R)-7 are rationalized by conformational
      analysis, comparison with the potent and specific group II mGluR agonist (-)
      LY379268 [(-)-12], and docking to a homology model of mGluR2.

PMID- 12213065
TI  - Novel antibiotics for the treatment of gram-positive bacterial infections.
AB  - The natural dipeptide antibiotic TAN 1057 A,B displays excellent antibacterial
      activity against staphylococci including methicillin resistant Staphylococcus
      aureus. However, the in vitro activity against additional Gram-positive strains,
      in particular pneumococci and Enterococcus faecalis, proved to be considerably
      lower. We report the synthesis and pharmacological evaluation of new derivatives
      of this natural product that displayed increased antibacterial potency against
      staphylococci and were also active against pneumococci. In particular, the
      analogues bearing modified beta-homoarginine side chains with methylated
      guanidine moieties were shown to be significantly more potent than the natural
      product TAN 1057 A,B.

PMID- 12213066
TI  - Acyclic nucleoside analogues as novel inhibitors of human mitochondrial thymidine
      kinase.
AB  - A series of acyclic nucleoside analogues of 5'-O-tritylthymidine have been
      synthesized and evaluated as potential human mitochondrial thymidine kinase (TK
      2) inhibitors. In this series, the sugar moiety of the parent 5'-O
      tritylthymidine has been replaced by aliphatic chains including (E)- and (Z)
      butenol, butynol, or butanol. Among them the (Z)-butenyl derivative (10) showed
      an IC(50) against TK-2 of 1.5 microM, being 1 order of magnitude more potent than
      the parent 5'-O-tritylthymidine. This lead compound has been further modified by
      replacing the thymine base by other pyrimidine bases such as 5-iodouracil, 5
      ethyluracil, 5-methylcytosine, 3-N-methylthymine, or 5,6-dihydrothymine, as well
      as by the purine base guanine. The trityl group has also been replaced by
      different aliphatic and aromatic acyl moieties including tert-butylacetyl,
      hexanoyl, decanoyl, and diphenylacetyl moieties. The evaluation of the compounds
      against TK-2 and the phylogenetically close HSV-1 TK has shown that the base
      moiety plays a crucial role in their interaction against these pyrimidine
      nucleoside kinases. Also, the presence of a lipophilic substituent,
      preferentially an aromatic moiety such as diphenylmethyl or triphenylmethyl, is
      required for efficient TK-2 inhibition. Whereas some compounds showed marked
      specificity for either TK-2 (i.e, the 5,6-dihydrothymine derivative, 26) or HSV-1
      TK (i.e., the butynyl derivative, 11), some others, including the (Z)-and (E)
      butenyl derivatives 10 and 12, showed significant inhibition against both
      enzymes. They also proved to be inhibitory against HSV-1 TK in intact human
      osteosarcoma cells that were transduced with the HSV-1 TK gene.

PMID- 12213067
TI  - N-[(2-Sulfo)-9-fluorenylmethoxycarbonyl](3)-gentamicin C(1) is a long-acting
      prodrug derivative.
AB  - Most low-molecular-weight drugs are short-lived species in the circulatory
      system, being rapidly eliminated by glomerular filtration in the kidney. However,
      binding to human serum albumin (HSA) can slow clearance and prolong lifetime
      profile in vivo. In this study, we have engineered a gentamicin derivative with
      affinity to albumin by linking three (2-sulfo)-9-fluorenylmethoxycarbonyl (FMS)
      to three amino groups of gentamicin C(1). FMS(3)-gentamicin associates with HSA
      with a K(a) value of (1.31 +/- 0.2) x 10(5) M(-1). It has less than 1% the
      antibacterial potency of native gentamicin. Upon incubation at pH 8.5 and 37
      degrees C, the FMS moieties from FMS(3)-gentamicin undergo slow hydrolysis
      (t(1/2) = 8.0 +/- 0.2 h), leading to a linear regeneration of the antibacterial
      potency with a t(1/2) value of 11 +/- 0.7 h. FMS(3)-gentamicin is a long-lived
      species in the rat circulatory system. Following a single subcutaneous or
      intravenous administration, it maintains a prolonged pharmacokinetic profile with
      a peak and a "through" concentration of immuno/antibacterial active gentamicin
      exceeding 4-5 times the duration obtained by administered native gentamicin. To
      sum up, an approach aimed at elongating the lifetime of low-molecular-weight
      drugs in vivo has been examined here with gentamicin. Two to three FMS per mole
      of compound are to be introduced to obtain an albumin associating affinity of
      K(d) = 7.6-9.2 microM and, hence, to significantly extend the drug's lifetime in
      situ following administration. By use of this technology, the loss of
      pharmacological potency with derivatization is of no consequence, since FMS
      moieties are hydrolyzed and activity is generated at physiological conditions.

PMID- 12213068
TI  - Anti-AIDS agents 49. Synthesis, anti-HIV, and anti-fusion activities of IC9564
      analogues based on betulinic acid.
AB  - The betulinic acid derivative IC9564 inhibits human immunodeficiency virus (HIV)
      1 entry. Among a series of IC9564 derivatives, 5 and 20 were the most promising
      compounds against HIV infection with EC(50) values of 0.33 and 0.46 microM,
      respectively. Both compounds inhibited syncytium formation with EC(50) values of
      0.40 and 0.33 microM, respectively. The comparable EC(50) values in the two
      assays suggested that these compounds are fusion inhibitors. The structure
      activity relationship data also indicated that a double bond in IC9564 can be
      eliminated and the statine moiety can be replaced with L-leucine while retaining
      anti-HIV activity.

PMID- 12213069
TI  - Synthesis of new molecular probes for investigation of steroid biosynthesis
      induced by selective interaction with peripheral type benzodiazepine receptors
      (PBR).
AB  - In the present study, we have synthesized and tested novel pyridopyrrolo- and
      pyrrolobenzoxazepine derivatives, as novel and selective peripheral type
      benzodiazepine receptor (PBR) ligands, and their ability to modulate steroid
      biosynthesis has been investigated. A subset of new ligands bind the PBR (rat
      brain and testis) with picomolar affinity, representing the most potent ligands
      that have been identified to date, and elicited effects on endogenous rate of
      steroidogenesis in MA10 Leydig cells, having similar potency and effect as
      PK11195. Several compounds, differently substituted at C-7, were used as
      molecular yardsticks to probe the spatial dimension of the lipophilic pocket L4
      in the receptor binding site.

PMID- 12213070
TI  - Novel structures derived from 2-[[(2-pyridyl)methyl]thio]-1H-benzimidazole as
      anti-Helicobacter pylori agents, Part 1.
AB  - 2-[[(2-Pyridyl)methyl]thio]-1H-benzimidazoles (2, sulfides) exhibit antibacterial
      properties that are selective for Helicobacter spp., but they also have an
      inherent susceptibility to metabolic oxidation to furnish 2-[[(2
      pyridyl)methyl]sulfinyl]-1H-benzimidazoles (1), which act as proton pump
      inhibitors (PPIs). We have discovered five compounds with retained antibacterial
      potency and selectivity in which the overall framework of the sulfides 2 could be
      kept intact while structural modifications were made to remove PPI activity.
      These compounds, 2-[((2-methyl-3-(2-(2-(2
      methoxyethoxy)ethoxy)ethylthio)phenyl)methyl)thio]-1H-benzimidazole (79), 2-[((2
      methyl-3-(2-(2-(2-(2-(2
      methoxyethoxy)ethoxy)ethoxy)ethoxy)ethylthio)phenyl)methyl)thio]-1H-benzimidazole
      (80), 2-[((2-methyl-3-((2-morpholino)ethylthio)phenyl)methyl)thio]-1H
      benzimidazole (86), 2-[[[2-methyl-3-[2-(2-methyl-5-nitroimidazol-1
      yl)ethylthio]phenyl]methyl]thio]-1H-benzimidazole (88), and 2-[[[2-methyl-3-[2
      (1,2,4-triazol-1-yl)ethylthio]phenyl]methyl]thio]-1H-benzimidazole (89), had
      minimum bactericidal concentrations (MBCs) of 0.5, 0.5, 1, 2, and 4 microg/mL,
      respectively. The reported compounds are bactericidal with MBCs within 1 order of
      magnitude of MBCs of clinically used antimicrobials such as clarithromycin (0.1
      microg/mL) or metronidazole (2-4 microg/mL) but differ from these inasmuch that
      they have an extremely narrow spectrum activity and appear to be species
      specific.

PMID- 12213071
TI  - Novel structures derived from 2-[[(2-pyridyl)methyl]thio]-1H-benzimidazole as
      anti-Helicobacter pylori agents, Part 2.
AB  - A parallel chemistry expansion of the 2-([3-[(1H-benzimidazol-2
      ylsulfanyl)methyl]-phenyl]sulfanyl)-1-ethanol scaffold (2) successfully provided
      a set of 2-([3-[(1H-benzimidazol-2-ylsulfanyl)methyl]-2
      methylphenyl]sulfanyl)ethyl carbamates with the generic structure 12, which
      displayed potent and selective activities against the gastric pathogen
      Helicobacter pylori. A prototype carbamate 12a was studied further and found to
      meet several significant in vitro microbiological criteria required for a novel
      anti-H. pylori agent. The compound displayed low minimal inhibition concentration
      (MIC) values against a panel of 27 different clinically relevant H. pylori
      strains (MIC(90) = 0.25 microg/mL), including strains resistant to either
      metronidazole or clarithromycin or both. Additionally, 12a was almost inactive
      against a wide range of commensal or pathogenic microorganisms comprising panels
      of 25 aerobic bacterial strains including two strains of methicillin resistant
      Staphylococcus aureus (MIC(90) = >64 microg/mL) and 18 anaerobic bacterial
      strains (MIC(90) = >64 microg/mL). The measured rate of resistance development
      against 12a was found to be less than 10(-9), a clinically acceptable level, and
      pharmacokinetic studies revealed in vivo exposure levels comparable with those
      established for antimicrobials currently used in H. pylori triple regimen.

PMID- 12213072
TI  - 2-Substituted 4-(thio)chromenone 6-O-sulfamates: potent inhibitors of human
      steroid sulfatase.
AB  - Steroid sulfatase (STS) has emerged as a highly attractive target for the therapy
      of a number of disorders. Starting with the known inhibitor estrone sulfamate (1)
      as lead compound and with the finding that steroid sulfamates containing a
      nonaromatic A-ring are inactive, chromen-4-one sulfamates were designed,
      prepared, and tested for their ability to block human STS. This new class of
      nonsteroidal inhibitors shows high potency when the sulfamate group and the side
      chain are situated in diagonally opposite positions (i.e., 2,6- and 3,7
      substitution pattern). The highest activity is achieved with fully branched,
      bulky aliphatic side chains and with thiochromen-4-one as the core element. 2-(1
      Adamantyl)-4H-thiochromen-4-on-6-O-sulfamate (6c) is the most potent STS
      inhibitor discovered so far, and it is about 170-fold superior to 1. As with 1,
      all chromenone sulfamates are irreversible inhibitors of STS with a biphasic time
      course of inactivation.

PMID- 12213073
TI  - Structure-activity relationships of the antimalarial agent artemisinin. 7. Direct
      modification of (+)-artemisinin and in vivo antimalarial screening of new,
      potential preclinical antimalarial candidates.
AB  - On the basis of earlier reported quantitative structure-activity relationship
      studies, a series of 9beta-16-(arylalkyl)-10-deoxoartemisinins were proposed for
      synthesis. Several of the new compounds 7 and 10-14 were synthesized employing
      the key synthetic intermediate 23. In a second approach, the natural product (+)
      artemisinic acid was utilized as an acceptor for conjugate addition, and the
      resultant homologated acids were subjected to singlet oxygenation and acid
      treatment to provide artemisinin analogues. Under a new approach, we developed a
      one step reaction for the interconversion of artemisinin 1 into artemisitene 22
      that did not employ selenium-based reagents and found that 2-arylethyliodides
      would undergo facile radical-induced conjugate addition to the exomethylene
      lactone of 22 in good yield. The lactone carbonyls were removed sequentially by
      diisobutylaluminum hydride reduction followed directly by a second reduction
      (BF(3)-etherate/Et(3)SiH) to afford the desired corresponding pyrans. Six
      additional halogen-substituted aromatic side chains were installed via 22
      furnishing the bioassay candidates 15-20. The analogues were examined for in
      vitro antimalarial activity in the W-2 and D-6 clones of Plasmodium falciparum
      and were additionally tested in vivo in Plasmodium berghei- and/or Plasmodium
      yoelii-infected mice. Several of the compounds emerged as highly potent orally
      active candidates without obvious toxicity. Of these, two were chosen for
      pharmacokinetic evaluation, 14 and 17.

PMID- 12213074
TI  - Monoclonal antibody conjugates of doxorubicin prepared with branched peptide
      linkers: inhibition of aggregation by methoxytriethyleneglycol chains.
AB  - High mole ratio BR96 immunoconjugates were synthesized using branched peptide
      doxorubicin linkers designed to liberate doxorubicin following antigen-specific
      internalization into lysosomes. However, these immunoconjugates are highly prone
      to noncovalent, dimeric aggregation. We hypothesize that this is due to (1) the
      hydrophobic nature of the peptides, (2) the loss of positive charge upon amide
      formation at the 3'-amino group of doxorubicin, and (3) the proximity of the
      peptide hydrophobic residues to form efficient intermolecular stacking
      interactions. By introducing a hydrophilic methoxytriethylene glycol chain onto
      the doxorubicin portion of the branched peptide linkers, aggregation has been
      eliminated or greatly reduced in the immunoconjugate products. The
      methoxytriethylene glycol chain was linked to the doxorubicin moiety of the
      linker via a hydrazone bond that is stable at pH 7 but hydrolyzes rapidly at pH 5
      to release free drug. BR96 immunoconjugates synthesized from methoxytriethylene
      glycol-modified branched peptide-doxorubicin linkers are highly potent and
      immunospecific in vitro. The data suggest that the methoxytriethylene glycol
      chain hydrolyzes as designed upon antigen-specific internalization into tumor
      lysosomes in vitro, where enzymatic degradation of the peptide linker releases
      free doxorubicin.

PMID- 12213076
TI  - Do structurally similar molecules have similar biological activity?
AB  - To design diverse combinatorial libraries or to select diverse compounds to
      augment a screening collection, computational chemists frequently reject
      compounds that are > or =0.85 similar to one already chosen for the combinatorial
      library or in the screening set. Using Daylight fingerprints, this report shows
      that for IC(50) values determined as a follow-up to 115 high-throughput screening
      assays, there is only a 30% chance that a compound that is > or = 0.85 (Tanimoto)
      similar to an active is itself active. Although this enrichment is greater than
      that found with random screening and docking to three-dimensional structures,
      this low fraction of actives within similar compounds occurs not only because of
      deficiencies in the Daylight fingerprints and Tanimoto similarity calculations
      but also because similar compounds do not necessarily interact with the target
      macromolecule in similar ways. The current study emphasizes the statistical or
      probabilistic nature of library design and that perfect results cannot be
      expected.

PMID- 12213075
TI  - Lysergamides of isomeric 2,4-dimethylazetidines map the binding orientation of
      the diethylamide moiety in the potent hallucinogenic agent N,N-diethyllysergamide
      (LSD).
AB  - Lysergic acid amides were prepared from (R,R)-(-)-, (S,S)-(+)-, and cis-2,4
      dimethyl azetidine. The dimethylazetidine moiety is considered here to be a rigid
      analogue of diethylamine, and thus, the target compounds are all conformationally
      constrained analogues of the potent hallucinogenic agent, N,N-diethyllysergamide,
      LSD-25. Pharmacological evaluation showed that (S,S)-(+)-2,4-dimethylazetidine
      gave a lysergamide with the highest LSD-like behavioral activity in the rat two
      lever drug discrimination model that was slightly more potent than LSD itself.
      This same diastereomer also had the highest affinity and functional potency at
      the rat serotonin 5-HT(2A) receptor, the presumed target for hallucinogenic
      agents, and a receptor affinity profile in a panel of screens that was most
      similar to that of LSD itself. Both cis- and the (R,R)-trans-dimethylazetidines
      gave lysergamides that were less potent in all relevant assays. The finding that
      the S,S-dimethylazetidine gave a lysergamide with pharmacology most similar to
      LSD indicates that the N,N-diethyl groups of LSD optimally bind when they are
      oriented in a conformation distinct from that observed in the solid state by X
      ray crystallography. The incorporation of isomeric dialkylazetidines into other
      biologically active molecules may be a useful strategy to model the active
      conformations of dialkylamines and dialkylamides.

PMID- 12213077
TI  - Inhibition of the antibacterial target UDP-(3-O-acyl)-N-acetylglucosamine
      deacetylase (LpxC): isoxazoline zinc amidase inhibitors bearing diverse metal
      binding groups.
AB  - UDP-3-O-[R-3-hydroxymyristoyl]-GlcNAc deacetylase (LpxC) is a zinc amidase that
      catalyzes the second step of lipid A biosynthesis in Gram negative bacteria.
      Known inhibitors of this enzyme are oxazolines incorporating a hydroxamic acid at
      the 4-position, which is believed to coordinate to the single essential zinc ion.
      A new structural class of inhibitors was designed to incorporate a more stable
      and more synthetically versatile isoxazoline core. The synthetic versatility of
      the isoxazoline allowed for a broad study of metal binding groups. Nine of 17
      isoxazolines, each incorporating a different potential metal binding functional
      group, were found to exhibit enzyme inhibitory activity, including one that is
      more active than the corresponding hydroxamic acid. Additionally, a designed
      affinity label inhibits LpxC in a time-dependent manner.

PMID- 12213078
TI  - Piperidine analogues of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3
      phenylpropyl)piperazine (GBR 12909): high affinity ligands for the dopamine
      transporter.
AB  - A series of 4-[2-[bis(4-fluorophenyl)methoxy]ethylpiperidines were examined for
      their ability to bind to the dopamine transporter (DAT), the norepinephrine
      transporter, and the serotonin transporter (SERT). In particular, the role of the
      N-substituent on affinity and selectivity for the DAT was probed. 4-[2-[Bis(4
      fluorophenyl)methoxy]ethyl-1-(2-naphthylmethyl)piperidine was found to possess
      subnanomolar affinity (K(i) = 0.7 nM) and good selectivity for the DAT (SERT/DAT
      = 323).

PMID- 12213080
TI  - Charles E. Braswell: a man with vision.
AB  - The purpose of this paper was to sketch a biography of Charles Edward Braswell,
      and to examine the contributions he made to the field of music therapy, including
      his work at Loyola University, his influence on the growth of music therapy in
      Louisiana. The paper also examined Braswell's involvement in the National
      Association for Music Therapy (NAMT), and his myriad contributions that
      influenced the growth and development of NAMT.

PMID- 12213081
TI  - The effects of different types of music on perceived and physiological measures
      of stress.
AB  - The effects of different types of music on perceived and physiological measures
      of stress were evaluated. Sixty undergraduate psychology students, 31 males and
      29 females, rated their level of relaxation and completed the State-Trait Anxiety
      Inventory (STAI) after they were told that they would be taking a stressful,
      mental test. Participants were randomly assigned to listen to different types of
      music or silence while skin temperature, frontalis muscle activity, and heart
      rate were recorded. Participants rated their relaxation and anxiety levels after
      listening to music or silence and completed the Mental Rotations Task Test.
      MANOVA's resulted in significant differences between groups for trait anxiety,
      F(57, 3) = 3.058, p =.036, and postmusic phase heart rate, F(57, 3) = 3.522, p
      =.021. Significant differences were also found between groups on state anxiety
      when trait anxiety was used as a covariate, F(57, 3) = 3.95, p =.024. The results
      of the research suggest that music may have an effect on the cognitive component
      of the stress response.

PMID- 12213082
TI  - Musically adapted social stories to modify behaviors in students with autism:
      four case studies.
AB  - The purpose of the present study was to investigate the effect of a musical
      presentation of social story information on the behaviors of students with
      autism. Social stories are a means of incorporating an individual with autism's
      propensity toward visual learning with educationally necessary behavior
      modifications. Participants in the study were four first- and second-grade
      students with a primary diagnosis of autism attending an elementary school in
      eastern Iowa. A unique social story was created for each student that addressed a
      current behavioral goal. Subsequently, original music was composed using the text
      of the social story as lyrics. The independent variable for this study was one of
      three treatment conditions: baseline (A); reading the story (B); and singing the
      story (C). The reading and singing versions of the social stories were
      alternately presented to the students using the counterbalanced treatment order
      ABAC/ACAB. The dependent variable was the frequency with which the target
      behavior occurred under each condition of the independent variable. Data were
      collected for a period of 1 hour following presentation of the social story.
      Results from all four cases indicated that both the reading condition (B) and the
      singing condition (C) were significantly (p <.05) more effective in reducing the
      target behavior than the no-contact control condition (A). The singing condition
      was significantly more effective than the reading condition only in Case Study
      III. For the remaining case studies, the mean frequency of the target behavior
      was smaller during the singing condition, but not significantly so. These results
      suggested that the use of a musically adapted version of social stories is an
      effective and viable treatment option for modifying behaviors with this
      population.

PMID- 12213083
TI  - The effect of a musical mood induction procedure on mood state-dependent word
      retrieval.
AB  - The purpose of this experiment was to replicate and expand upon an earlier study
      by Thaut and de l'Etoile (1993) by examining the effect of a musical mood
      induction procedure on mood state-dependent word retrieval. Participants (N = 45)
      completed a 2-day testing procedure. On day one, participants read a list of
      adjectives and wrote down an antonym for each one. On day two, participants
      recalled as many of the antonyms as possible. During the testing procedure,
      participants were placed in 1 of 4 conditions: (a) mood induction at encoding,
      (b) mood induction at recall, (c) no mood induction, and (d) mood induction at
      both encoding and recall. The mood induction procedure included 3 steps.
      Participants first assessed their current mood state using a visual analog scale.
      They then listened to music for 5 minutes, determined the mood of the piece while
      listening, and tried to match their mood to the music. Finally, participants
      again used the visual analog scale to indicate their mood. Results indicated that
      participants who received mood induction prior to both encoding and recall were
      able to retrieve significantly more words than participants who did not undergo
      any mood induction. The results are discussed in light of the associative network
      theory of memory and emotions and the treatment of mood disorders.

PMID- 12213084
TI  - Polyunsaturated fatty acids decrease the expression of sterol regulatory element
      binding protein-1 in CaCo-2 cells: effect on fatty acid synthesis and
      triacylglycerol transport.
AB  - Regulation of sterol regulatory element-binding proteins (SREBPs) by fatty acid
      flux was investigated in CaCo-2 cells. Cells were incubated with 1 mM
      taurocholate with or without 250 microM 18:0, 18:1, 18:2, 20:4, 20:5 or 22:6
      fatty acids. Fatty acid synthase (FAS) and acetyl-CoA carboxylase mRNA levels and
      gene and protein expression of SREBPs were estimated. 18:2, 20:4, 20:5 and 22:6
      fatty acids decreased the amount of mature SREBP-1 and mRNA levels of SREBP-1c,
      SREBP-1a, FAS and acetyl-CoA carboxylase. SREBP-2 gene or mature protein
      expression was not altered. Liver X receptor (LXR) activation by T0901317
      increased gene expression of SREBP-1c, SREBP-1a, FAS and acetyl-CoA carboxylase
      without altering SREBP-2. 20:5, but not 18:1, prevented the full expression of
      SREBP-1c mRNA by T0901317. T0901317 increased SREBP-1 mass without altering the
      mass of mature SREBP-2. Although only 18:2, 20:4, 20:5 and 22:6 suppressed SREBP
      1, acetyl-CoA carboxylase and FAS expression, all fatty acids decreased the rate
      of fatty acid synthesis. T0901317 increased endogenous fatty acid synthesis yet
      did not increase secretion of triacylglycerol-rich lipoproteins. In CaCo-2 cells,
      polyunsaturated fatty acids decrease gene and protein expression of SREBP-1 and
      FAS mRNA, probably through interference with LXR activity. Since all fatty acids
      decreased fatty acid synthesis, mechanisms other than changes in SREBP-1c
      expression must be entertained. Increased endogenous fatty acid synthesis does
      not promote triacylglycerol-rich lipoprotein secretion.

PMID- 12213085
TI  - The carp muscle-specific sub-isoenzymes of creatine kinase form distinct dimers
      at different temperatures.
AB  - We have previously cloned three muscle-specific sub-isoforms of creatine kinase
      (CK, EC 2.7.3.2) from the common carp ( Cyprinus carpio ), designated M1-CK, M2
      CK, and M3-CK. The enzyme has a key role in maintaining the energy homoeostasis
      of cells with fluctuating energy requirements. In the present paper, we report
      that all three M-CKs in the red and white muscle of different temperature
      acclimatized carp were ubiquitously distributed in the cytosol and along
      membranes. In addition, the expression levels of these isoforms were not
      significantly altered in response to the temperature acclimatization.
      Interestingly, our studies showed that the formation of distinct homo- or
      heterodimers among these three M-CKs was found at various temperatures. At higher
      temperature, the M1M1-CK and M2M2-CK homodimers, and the M1M3-CK heterodimer are
      the predominant MM-CKs, whereas the M3M3-CK achieves its homodimeric state at
      lower temperature. We postulated testable homology models to investigate the
      chemical properties of these dimeric interfaces. M1M1-CK was used as a reference
      to compare the structural differences with the M3M3-CK dimer. The calculated
      solvent accessible surface area that was buried in the contact interfaces of the
      M1M1-CK and M3M3-CK dimers showed an overall decrease of 12% in the M3M3-CK
      interface. The modelling analysis also suggested a net decrease of twelve
      hydrophobic residues and a Phe(3)-->Lys substitution in the M3M3-CK interface. An
      increase in thermolability of the M3M3-CK homodimer might be due to the decrease
      in subunit ion pairs and buried surface area in this dimer. Based on our
      findings, we propose that the carp-muscle-specific CK isoenzymes could undergo
      shuffling to form distinct M-CK homo- or heterodimers in acclimatization to
      environmental temperatures.

PMID- 12213087
TI  - Rac and rho: the story behind melanocyte dendrite formation.
AB  - Melanocyte dendrites are hormonally responsive actin and microtubule containing
      structures whose primary purpose is to transport melanosomes to the dendrite tip.
      Melanocyte dendrites have been an area of intense interest for melanocyte
      biologists, but it was not until recently that we began to understand the
      mechanisms underlying their formation. In contrast with melanogenesis, for which
      numerous mutations in pigment producing genes and mouse models have been
      identified, a genetic defect resulting in impaired dendrite formation has not
      been found. Therefore, much of the insight into melanocyte dendrites has come
      from electron microscopy or in vitro culture systems of normal human and murine
      melanocytes as well as melanoma cell lines. The growth factors that regulate the
      formation of melanocyte dendrites have been thoroughly studied and it is clear
      that multiple signalling systems are able to stimulate, and in some cases
      inhibit, dendrite formation. Recent data points to the Rho family of small
      guanosine triphosphate (GTP)-binding proteins as master regulators of dendrite
      formation, particularly Rac and Rho. In this review I will summarize the progress
      scientists have made in understanding the structure, hormonal regulation and
      molecular mediators of melanocyte dendrite formation.

PMID- 12213088
TI  - Approaches to repigmentation of vitiligo skin: new treatment with ultrasonic
      abrasion, seed-grafting and psoralen plus ultraviolet A therapy.
AB  - Vitiligo vulgaris is a common disease throughout the world although its
      pathogenesis is not yet known. The most frequent treatment used for vitiligo is
      PUVA (psoralen plus ultraviolet A) and topical steroids but against stable
      refractory vitiligo, various other surgical techniques have been developed such
      as autografting, epidermal grafting with suction blisters, epithelial sheet
      grafting, and transplantation of cultured melanocytes. We have discovered a new
      method using ultrasonic abrasion, seed-grafting and PUVA therapy. The ultrasonic
      surgical aspirator abrades only the epidermis of recipient sites. This easily and
      safely removes only the epidermis, even on spotty lesions or intricate regions
      which are difficult to remove using a conventional motor-driven grinder or liquid
      nitrogen. Epidermal seed-grafting can cover more area than sheet-grafting, and
      subsequent PUVA treatment can enlarge the area of pigmentation with coalescence
      of adjacent grafts. In this article, we provide a general overview of the current
      surgical therapies including our method for treating stable refractory vitiligo.

PMID- 12213089
TI  - Modulation of melanogenesis by aloesin: a competitive inhibitor of tyrosinase.
AB  - Aloesin, [2-acetonyl-8-beta-d-glucopyranosyl-7-hydroxy-5-methylchromone], a
      compound isolated from the Aloe plant, is shown in these studies to modulate
      melanogenesis via competitive inhibition of tyrosinase. Aloesin inhibits purified
      tyrosinase enzyme and specifically inhibits melanin production in vitro. Enzyme
      kinetics studies using normal human melanocyte cell lysates and cell-based
      melanin production demonstrated that aloesin is a competitive inhibitor of
      tyrosinase from mushroom, human and murine sources. Tyrosine hydroxylase and 3,4
      dihydroxyphenylalanine (DOPA) oxidase activities of tyrosinase from normal human
      melanocyte cell lysates were inhibited by aloesin in a dose dependent manner. In
      a percutaneous absorption study a finite dose of aloesin penetrated the skin
      slowly and was recovered primarily in the surface wash. Aloesin shows promise as
      a pigmentation-altering agent for cosmetic or therapeutic applications.

PMID- 12213090
TI  - Membranes of retinal pigment epithelial cells in vitro are damaged in the
      phagocytotic process of the photoreceptor outer segment discs peroxidized by
      ferrous ions.
AB  - The ferrous ions released from haemoglobin and storage-transferrin ions cause
      oxidative stress in the eyes. We observed the phagocytotic process of the
      photoreceptor outer segment discs peroxidized by ferrous ions in the retinal
      pigment epithelial (RPE) cells in vitro, and investigated how the ferrous ions
      influenced RPE in vitro and the photoreceptor outer segment discs. We obtained
      isolated photoreceptor outer segment discs using sucrose gradient of specific
      gravity after homogenizing porcine retinas. After bovine RPE cells were cultured
      with isolated photoreceptor outer segment discs containing FeCl2 for 5 and 24 h,
      we incubated the specimens with rhodamine phalloidin, antimouse alpha-tubulin
      antibody and antimouse Ig G (FITC and rhodamine labelled). We observed the
      specimens by a laser scanning microscopy, and made the ultrathin sections with or
      without 2% uranyl acetate and 2% lead acetate for examination by transmission
      electron microscopy. Actin filaments and microtubules of specialized cells such
      as RPE cells were actively involved in phagocytosis of the photoreceptor outer
      segment discs. Microtubules were damaged during the phagocytotic process of the
      photoreceptor outer segment discs peroxidized by ferrous ions. The peroxidation
      increased the granular and aggregated autofluorescence of the photoreceptor outer
      segment discs. The membranes of the disc and the phagosomes, and lysosomes in RPE
      cells were damaged by ferrous ions and had fine particles with high electron
      density staining without uranium acetate and lead citrate. The cytoskeletons such
      as actin filaments and microtubules, and the membranes of the phagosomes and the
      lysosomes in RPE cells in vitro were damaged during the phagocytotic process of
      the photoreceptor outer segment discs peroxidized by ferrous ions.

PMID- 12213091
TI  - Changes in the proliferative activity of epidermal melanocytes in serum-free
      primary culture during the development of ultraviolet radiation B-induced
      pigmented spots in hairless mice.
AB  - Long-term exposure to ultraviolet radiation B (UVB) induced pigmented spots in
      the dorsal skin of hairless mice of strain (HR-1 X HR/De)F1. To clarify the
      cellular mechanism for the development of these UVB-induced pigmented spots, we
      investigated changes in the proliferative activity of epidermal melanoblasts and
      melanocytes in the dorsal skin at various weeks after UVB irradiation. Epidermal
      cell suspensions from the dorsal skin of hairless mice were cultured in a serum
      free medium supplemented with dibutyryl adenosine 3':5'-cyclic monophosphate
      (DBcAMP) and basic fibroblast growth factor (bFGF). The suspensions were prepared
      from dorsal skins of mice exposed to UVB for 4 weeks (the stage of
      hyperpigmentation). Suspensions were also prepared from mice at 3 (the stage of
      depigmentation), 8 (the stage of appearance of pigmented spots), 20 (the stage of
      development of small-sized pigmented spots) and 37 (the stage of development of
      medium-sized pigmented spots) weeks after the cessation of 8-week UVB exposure.
      At the stage of hyperpigmentation the proliferative activity of melanoblasts and
      melanocytes was suppressed. With the development of pigmented spots, the
      proliferative activity of undifferentiated melanoblasts gradually increased, and
      then followed the increase in the proliferative activity of differentiated
      melanocytes. These results suggest that the proliferative activity of epidermal
      melanoblasts and melanocytes in UVB-irradiated skin increases with the
      development of pigmented spots.

PMID- 12213092
TI  - Regulatory control of both microtubule- and actin-dependent fish melanosome
      movement.
AB  - In fish melanophores, melanosomes can either aggregate around the cell centre or
      disperse uniformly throughout the cell. This organelle transport involves
      microtubule- and actin-dependent motors and is regulated by extracellular stimuli
      that modulate levels of intracellular cyclic adenosine 3-phosphate (cAMP). We
      analysed melanosome dynamics in Atlantic cod melanophores under different
      experimental conditions in order to increase the understanding of the regulation
      and relative contribution of the transport systems involved. By inhibiting dynein
      function via injection of inhibitory antidynein IgGs, and modulating cAMP levels
      using forskolin, we present cellular evidence that dynein is inactivated by
      increased cAMP during dispersion and that the kinesin-related motor is
      inactivated by low cAMP levels during aggregation. Inhibition of dynein further
      resulted in hyperdispersed melanosomes, which subsequently reversed movement
      towards a more normal dispersed state, pointing towards a peripheral feedback
      regulation in maintaining the evenly dispersed state. This reversal was blocked
      by noradrenaline. Analysis of actin-mediated melanosome movements shows that
      actin suppresses aggregation and dispersion, and indicates the possibility of
      down-regulating actin-dependent melanosome movement by noradrenaline. Data from
      immuno-electron microscopy indicate that myosinV is associated with fish
      melanosomes. Taken together, our study presents evidence that points towards a
      model where both microtubule- and actin-mediated melanosome transport are
      synchronously regulated during aggregation and dispersion, and this provides a
      cell physiological explanation behind the exceptionally fast rate of background
      adaptation in fish.

PMID- 12213093
TI  - Type I gamma-GT mRNA is expressed in B16 melanoma and levels correlate with
      pigmentation.
AB  - Gamma-glutamyl transpeptidase (gamma-GT), an ectoenzyme involved mainly in
      glutathione metabolism, is expressed in B16 melanoma cells. B16 melanoma cells
      under continuous culture conditions show a phenotypic drift from melanotic to
      amelanotic and re-melanotic stages. We have investigated the regulation of gamma
      GT in B16 melanoma cells under such different pigmentary conditions. High levels
      of gamma-GT messenger RNA (mRNA) and activity were detected in pigmented B16
      melanoma cells, whereas in amelanotic B16 melanoma cells the levels were very
      low. Treatment with lactic acid, a known inhibitor of tyrosinase gene expression,
      also led to the down-regulation of gamma-GT mRNA and activity. Thus our results
      indicate that gamma-GT regulation depends on the pigmentation status in pigment
      cells. We have also assessed the levels of gamma-GT in normal murine melanocytes
      (melan-a cells). It was seen that melan-a cells express very low levels of gamma
      GT. As gamma-GT is known to be regulated in a tissue-specific manner, and is
      expressed from as many as six promoters giving rise to six different types of
      mRNAs each having unique 5' ends, we have further investigated the type of gamma
      GT mRNA expressed in B16 melanoma and melan-a cells. In this study, we have
      conclusively demonstrated that type I mRNA transcript of gamma-GT is expressed in
      B16 melanoma and melan-a cells.

PMID- 12213094
TI  - Tissue plasminogen activator is released into cultured medium by cultured human
      uveal melanocytes.
AB  - Melanoma cells produce tissue plasminogen activator (t-PA) that plays an
      important role in tumor invasion and metastasis. The production of t-PA by normal
      human uveal melanocytes has not been reported previously. In order to explore
      this possibility, we studied the production of t-PA by cultured human uveal
      melanocytes and compared that with the production by cultured human uveal
      melanoma cells and epidermal melanocytes. Human adult uveal melanocytes were
      isolated and cultured from donor eyes. The cells were cultured in serum-free
      medium for 48 h and the conditioned medium then collected for the plasminogen
      activator (PA) activity assay. Free PA activity was tested in an amidolytic assay
      using a t-PA standard curve. PA type was identified by fibrinography and
      antihuman t-PA and urokinase plasminogen activator (u-PA) blocking antibodies.
      Free PA activity was found in the conditioned medium of normal melanocytes and
      melanoma cells. The predominant PA activity was t-PA. Normal uveal melanocytes
      produced more t-PA (3.23 +/- 0.73 IU/105 cells/24 h) than that of epidermal
      melanocytes (1.25 IU/105 cells/24 h) but much less than uveal melanoma cells
      (11.0 +/- 3.39 IU/105 cells/24 h). Western blot analysis revealed that most t-PA
      in conditioned media were one-chain t-PA with molecular weight of 69 kDa. Our
      study indicates that uveal melanocytes may contribute to the free t-PA activity
      previously found in aqueous humor and choroidal eye cup superfusions. Therefore,
      this function of uveal melanocytes may play a role in intraocular matrix
      remodeling, fibrinolysis and aqueous humor outflow.

PMID- 12213095
TI  - Comparing quantitative measures of erythema, pigmentation and skin response using
      reflectometry.
AB  - We measured a number of pigmentation and skin response phenotypes in a sample of
      volunteers (n=397) living in State College, PA. The majority of this sample was
      composed of four groups based on stated ancestry: African-American, European
      American, Hispanic and East Asian. Several measures of melanin concentration (L*,
      melanin index and adjusted melanin index) were estimated by diffuse reflectance
      spectroscopy and compared. The efficacy of these measures for assessing
      constitutive pigmentation and melanogenic dose-response was evaluated. Similarly,
      several measures of erythema (a*, erythema index and adjusted erythema index)
      were compared and evaluated in their efficacy in measuring erythema and erythemal
      dose-response. We show a high correspondence among all of the measures for the
      assessment of constitutive pigmentation and baseline erythema. However, our
      results demonstrate that evaluating melanogenic dose-response is highly dependent
      on the summary statistic used: while L* is a valid measure of constitutive
      pigmentation it is not an effective measure of melanogenic dose-response. Our
      results also confirm the use of a*, as it is shown to be highly correlated with
      the adjusted erythema index, a more advanced measure of erythema based on the
      apparent absorbance. Diffuse reflectance spectroscopy can be used to quantify the
      constitutive pigmentation, melanogenic dose-response at 7 d and erythemal dose
      response at both 24 h and 7 d postexposure.

PMID- 12213096
TI  - Skin responses to ultraviolet radiation: effects of constitutive pigmentation,
      sex, and ancestry.
AB  - Constitutive skin pigmentation and skin responses to ultraviolet radiation were
      measured on a sample of volunteers (n=250) living in State College, PA, USA. The
      sample was composed of individuals of European American (n=190), Hispanic (n=45),
      and East Asian ancestry (n=15). Constitutive pigmentation was measured using the
      Adjusted Melanin Index (AMI), Erythemal Dose Response (EDR) was measured using
      the slope of a* at 24 h (Deltaa*), and Melanogenic Dose-Response (MDR) was
      measured using DeltaAM, the slope of AMI at 7 d. The relationships between
      constitutive skin pigmentation, EDR, MDR, sex, age, and ancestry were
      investigated. European Americans showed a lower constitutive pigmentation, had a
      significantly higher burn response (EDR), and had a significantly lower tanning
      response (MDR) than Hispanics and East Asians. No significant difference is seen
      between Hispanics and East Asians for either constitutive pigmentation or EDR.
      Constitutive pigmentation in females was slightly lower than in males in all
      three samples, but the difference was not significant. While no differences were
      observed in MDR between sexes, males had a stronger EDR than females regardless
      of population or constitutive pigmentation level, and this difference was
      significant in European Americans and Hispanics. We observed no age-related
      differences in any of the populations or measures investigated. We evaluated the
      relationship between constitutive pigmentation, EDR and MDR. There was a strong
      inverse correlation between constitutive pigmentation and EDR in the three
      samples (European Americans, R2=0.176, P < 0.001; Hispanics, R2=0.204, P=0.009;
      East Asians, R2=0.223, P=0.098) and a strong direct correlation between
      constitutive pigmentation and MDR in European Americans and Hispanics (European
      Americans, R2=0.094, P < 0.001; Hispanics, R2=0.164, P=0.012). In other words,
      persons with lower constitutive pigmentation both burn more and tan less than
      persons with higher pigmentation. However, after controlling for constitutive
      pigmentation, EDR and MDR were significantly correlated in European Americans
      (R2=0.041 P=0.006). Thus, the general observation that persons who burn more tan
      less is probable because of the common link that these two phenotypes have with
      constitutive skin pigmentation and, in fact, once pigmentation has been adjusted
      for, there is a positive correlation between tanning response and burning
      response in European Americans.

PMID- 12213097
TI  - Keratinocytes control the proliferation and differentiation of cultured epidermal
      melanocytes from ultraviolet radiation B-induced pigmented spots in the dorsal
      skin of hairless mice.
AB  - Long-term exposure of ultraviolet radiation B (UVB)-induced pigmented spots in
      the dorsal skin of hairless mice of Hos:(HR-1 X HR//De) F1. Previous study showed
      that the proliferative and differentiative activities of cultured epidermal
      melanoblasts/melanocytes from UVB-induced pigmented spots increased with the
      development of the pigmented spots. To determine whether the increase in the
      proliferative and differentiative activities of epidermal
      melanoblasts/melanocytes was brought about by direct changes in melanocytes, or
      by indirect changes in surrounding keratinocytes, pure cultured
      melanoblasts/melanocytes and keratinocytes were prepared and co-cultured in
      combination with control and irradiated mice in a serum-free culture medium.
      Keratinocytes from irradiated mice stimulated the proliferation and
      differentiation of both neonatal and adult non-irradiated
      melanoblasts/melanocytes more greatly than those from non-irradiated mice. In
      contrast, both non-irradiated and irradiated adult melanocytes proliferated and
      differentiated similarly when they were co-cultured with irradiated adult
      keratinocytes. These results suggest that the increased proliferative and
      differentiative activities of mouse epidermal melanocytes from UVB-induced
      pigmented spots are regulated by keratinocytes, rather than melanocytes.

PMID- 12213099
TI  - Electrical behaviour of interleukin-1 beta (IL-1 beta) and prostaglandin-E2
      (PGE2) on colonic myenteric neurones.
AB  - Abstract Intracellular recordings were used to examine the effects on electrical
      and synaptic behaviour of interleukin (IL)-1beta and prostaglandin E2(PGE2) on
      myenteric neurones of the guinea-pig colon. Application of IL-1beta and
      PGE2resulted in a concentration-dependent slow depolarization with enhanced spike
      discharge in, respectively, 45% (21/47) and 83% (33/41) of the impaled colonic
      neurones. Administration of IL-1beta in three neurones (6%) elicited a
      hyperpolarization. Responses remained during tetrodotoxin application, indicative
      of a direct effect of both substances on the impaled neurones. The effects of IL
      1beta remained in the presence of indomethacine, a prostaglandin synthase
      inhibitor. Responses were seen in both nitric oxide synthase- and choline acetyl
      transferase-immunoreactive neurones. IL-1beta evoked a 26% reduction of the fast
      excitatory postsynaptic potential. These results indicate that the application of
      IL-1beta and PGE2evoke direct excitatory actions on a subset of myenteric
      neurones. For IL-1beta, direct inhibition and presynaptic inhibition of the fast
      excitatory postsynaptic potential has also been found. In the distal colon,
      responses to IL-1beta are not mediated through PGE2pathways.

PMID- 12213100
TI  - Human duodenal phase III migrating motor complex activity is predominantly
      antegrade, as revealed by high-resolution manometry and colour pressure plots.
AB  - Abstract Late phase III migrating motor complex activity has been said to be
      primarily retroperistaltic but has not been assessed with high resolution
      manometry or three-dimensional colour pressure plots (pressure/time/distance).
      Duodenal phase III was examined in healthy young volunteers (seven male, two
      female) with a 20-lumen assembly. With the most proximal sidehole in the distal
      antrum, after a 4.5-cm interval 18 sideholes at 1.5-cm intervals spanned the
      duodenum with a final sidehole 3 cm beyond. Fasting pressures were recorded until
      phase III occurred. Comparisons were made between proximal (P) and distal (D)
      duodenum during early (E) (first 0.5-1 min) and late (L) (last 0.5-1 min) phase
      III. With colour pressure analysis, 121 of 180 pressure wave (PW) sequences were
      purely antegrade, two purely retrograde and 57 bidirectional. Ten of fifty-seven
      bidirectional PW sequences were complex, branching to become two separate
      sequences. Bidirectional sequences occurred more frequently in late than early
      phase III (L 43 vs. E 14 of 57), but their occurrence did not differ between
      proximal and distal duodenum (P31 vs. D 24 of 57). Antegrade propagation velocity
      was faster in late compared with early phase III (L 28.50 vs. E 17.05 mm s(-1); P
      = 0.006), but did not differ between proximal and distal duodenum. Colour
      pressure analysis also indicated an intermittent segmental pattern to phase III,
      with each subject exhibiting a change in velocity or direction, or a relative
      failure of peristalsis somewhere along the duodenum during part of phase III.
      Duodenal phase III is not homogenous and, in contrast with previous studies, does
      not primarily constitute a retroperistaltic pump. Colour pressure analysis is
      useful in interpreting intraluminal pressure profiles and may improve the
      sensitivity and specificity of clinical studies.

PMID- 12213101
TI  - Relationship between colonic motility and cholinergic mechanosensory afferent
      synaptic input to mouse superior mesenteric ganglion.
AB  - Abstract Abdominal prevertebral ganglion neurones receive excitatory synaptic
      input from intestinofugal neurones. To better understand the physiological
      significance of this input, we examined the relationship between synaptic input
      to mouse superior mesenteric ganglion (SMG) neurones and intracolonic pressure
      and volume changes that accompany spontaneous colonic contractions in vitro.
      Electrical activity was recorded intracellularly from SMG neurones in ganglia
      attached to a segment of distal colon. The majority of neurones examined received
      ongoing fast excitatory potentials (F-EPSPs). F-EPSP frequency increased when the
      colon was distended with fluid and during spontaneous increases in colonic volume
      that accompanied colonic relaxation. In contrast, F-EPSP frequency in SMG
      neurones decreased when the colon emptied, and remained at a reduced frequency
      until the colon refilled and volume increased. Nicotinic blockade of the colon
      abolished spontaneous colonic contractions and reduced or abolished synaptic
      input to SMG neurones, suggesting that most of the synaptic input arose from
      second or higher order neurones. Retrograde labelling identified cell bodies of
      intestinofugal neurones in myenteric ganglia. Most had short, club-like dendritic
      processes and appeared uni-axonal. These results show that mechanosensory
      intestinofugal afferent nerves monitor intracolonic volume changes.

PMID- 12213102
TI  - Small intestinal transections decrease the occurrence of tapeworm-induced
      myoelectric patterns in the rat.
AB  - Abstract Luminal infection by the noninvasive tapeworm, H. diminuta, alters rat
      small intestinal myoelectric activity. The significance of continuity between
      small intestinal enteric nervous system (ENS) and that of both the
      stomach/pylorus and colon/caecum regarding the induction of tapeworm-altered
      myoelectric patterns was evaluated. A total of 32 rats were implanted with four
      serosal electrodes placed at sites in the duodenum through the mid-jejunum.
      Sixteen of the 32 rats underwent intestinal transections and anastomoses at both
      the duodenum and ileum. After recording myoelectrical activity of both normal and
      transected intestines, eight rats from each group (normal and transected) were
      infected with H.diminuta. Phase III frequency, duration of the migrating
      myoelectric complex (MMC), slow wave frequency, percentage of slow waves
      associated with spike potentials and the occurrence of the the two tapeworm
      initiated myoelectric patterns, repetitive bursts of action potentials (RBAP) and
      sustained spike potentials (SSP), were measured. In infected rats, the frequency
      of the RBAP and SSP electric patterns were significantly reduced by the double
      transection. Intestinal transection did not affect the other changes caused by
      infection, such as decreased MMC phase III frequency and percentage of slow waves
      associated with spike potentials. In conclusion, a small intestinal ENS in
      continuity with other segments of the GI tract is required to generate maximal
      numbers of tapeworm-induced SSP and RBAP myoelectric activity in the small
      intestine of the rat.

PMID- 12213103
TI  - Anisotropic propagation in the small intestine.
AB  - Abstract Measuring propagation anisotropy may help in determining the tissue
      layers involved in the propagation of electrical impulses in the intestine. We
      used 240 extracellular electrograms recorded from the isolated feline duodenum.
      The conduction velocities of slow waves and of individual spikes were measured
      from their site of origin into all directions. Both slow waves and spikes
      propagate anisotropically in the small intestine but in different directions and
      to a different degree. Slow waves propagated anisotropically faster in the
      circumferential (1.7 +/- 0.8 cm s(-1)) than in the axial direction (1.3 +/- 0.5
      cm s(-1); P < 0.001). Spikes, on the other hand, propagated faster in the
      longitudinal direction (7.8 +/- 4.5 cm s(-1)) than in the circumferential
      direction (3.3 +/- 4.3 cm s(-1); P < 0.001). Furthermore, the average conduction
      velocity of spikes (6.3 +/- 4.5 cm s(-1)) was significantly higher than that of
      slow waves (1.5 +/- 1.1 cm s(-1); P < 0.001). The anisotropic propagation of
      spikes supports the argument that these propagate in the longitudinal muscle
      layer. The anisotropic propagation of slow waves may be the result of the
      interaction between the myenteric layer of interstitial cells of Cajal and their
      electrotonic connection to both the longitudinal and the circular muscle layer.

PMID- 12213104
TI  - Sensory-motor responses to volume-controlled duodenal distension.
AB  - Abstract Visceral perception and secondary peristalsis evoked by distension of
      the duodenum were studied in 10 healthy volunteers. An impedance planimetric
      probe for cross-sectional area (CSA) measurements inside a balloon and with three
      pressure channels was used. Balloon distensions were performed in the fed state
      with or without the administration of the antimuscarinic drug butylscopolamine. A
      modified questionnaire was used to assess the nonpainful and painful sensations.
      The total tension (T(total)) and the passive tension (T(passive)) were determined
      from the distensions without and with the administration of butylscopolamine,
      respectively. The active tension (T(active)) was T(total) - T(passive). The
      stepwise balloon distensions induced the first sensation at a volume of 33 +/- 3
      mL. After administration of butylscopolamine the first sensation appeared at 42
      +/- 1 mL. The perception score (PS) revealed an approximately linear increase as
      function of volume, CSA, pressure and tension after the first sensation.
      Butylscopolamine resulted in significant changes in PS score as function of
      volume, CSA and strain, but not as a function of pressure and tension. The
      frequency of the secondary peristalsis increased to the highest value (8.2 +/-
      0.8 contractions min(-1)) at a volume of 21 mL. Butylscopolamine almost abolished
      the distension-evoked motility. T(total) and T(passive) increased nonlinearly as
      a function of volume, whereas T(active) increased up to a distension volume of 33
      mL and then decreased at higher volumes. Hence, the conventional length-tension
      diagrams as known from studies of smooth muscle strips in vitro can be reproduced
      in the human duodenum in vivo. This new way of studying intestinal sensation and
      motility may prove to have both basic and clinical importance as both passive
      tissue structures and the sensorimotor function are tested.

PMID- 12213105
TI  - In search of objective manometric criteria for colonic high-amplitude propagated
      pressure waves.
AB  - Abstract The aims of this study were to explore all characteristics of high
      amplitude propagated contractions (HAPCs) that would allow them to be
      distinguished from nonHAPC colonic pressure waves, and to develop computer
      algorithms for automated HAPC detection. Colonic manometry recordings obtained
      from 24 healthy volunteers were used. Automated analysis was performed to detect
      propagated pressure waves and to determine their amplitude, duration and area
      under the curve (AUC). For each of these variables distribution plots were made.
      Automated HAPC counts were compared to visual counts by experienced
      investigators. Distribution plots of 141093 colonic pressure waves lacked a
      bimodal pattern, as was also the case for propagated contractions (n = 8758).
      With increasing high-amplitude thresholds for HAPC detection, a gradual decrease
      in the automatically detected HAPC number was observed. These findings precluded
      determination of a threshold. Taking visually detected HAPCs as reference,
      amplitude thresholds of 100 mmHg in two channels, and 80 mmHg in one channel
      yielded the highest sensitivity (92%). In conclusion, objective criteria to
      distinguish HAPCs from other propagated pressure waves on the basis of their
      amplitude, duration or AUC do not exist. Automated detection of HAPCs using
      empirically derived criteria leads to an acceptable degree of correlation with
      visually detected HAPCs.

PMID- 12213106
TI  - Distinct regional expression of SNARE proteins in the feline oesophagus.
AB  - Abstract Soluble N-ethylmaleimide-sensitive factors attachment protein receptors
      (SNAREs), initially found to mediate membrane fusion, have now been shown to also
      bind and regulate a number of membrane ion channels in neurones and
      neuroendocrine cells. We recently reported that the SNARE protein SNAP-25
      regulates Ca(2+)- activated (K(Ca)) and delays rectifier K(+) channels (K(V)) in
      oesophageal smooth muscle cells. This raised the possibility that cognate and
      other SNARE proteins could also be present in the oesophageal smooth muscle cell
      to regulate these and other functions. Circular muscle tissue sections and single
      freshly isolated muscle cells from the oesophageal body circular and longitudinal
      layers, and from lower oesophageal sphincter clasp and sling regions were
      studied. The subcellular location of SNAP-23, SNAP-25, syntaxins 1 to 4, and
      vesicle-associated membrane protein (VAMP)-2 were explored using a laser scanning
      confocal imaging system. Feline oesophageal smooth muscle of all regions examined
      demonstrated the presence of SNAP-23, SNAP-25, syntaxins 1 to 4, and VAMP-2 on
      the plasma membrane. The intensity of these syntaxins and SNAP-25/-23 proteins
      varied between the different muscle groups of the oesophagus. In some regions,
      some SNARE proteins were also noted in the muscle cell cytoplasm. No differential
      expression was found for VAMP-2. The differential expression of SNAP-25 and its
      regulation of K(+) channels indicate the important role of SNAP-25 in regulating
      the distinct membrane excitability and contractility along the smooth muscle of
      the oesophagus. This is further contributed by its interactions with the cognate
      syntaxins, which are also differentially expressed in the muscle groups of the
      oesophageal body and lower oesophageal sphincter (LOS). These SNARE proteins
      probably have other functions in the smooth muscle cell, such as regulating
      vesicular transport processes.

PMID- 12213107
TI  - Effect of the selective serotonin reuptake inhibitor sertraline on gastric
      sensitivity and compliance in healthy humans.
AB  - Abstract Visceral hypersensitivity may contribute to symptoms in functional
      dyspepsia. Selective serotonin reuptake inhibitors (SSRIs) may be beneficial in
      functional gastrointestinal disorders. The aim of this study was to determine
      whether the SSRI sertraline affects gastric sensitivity and compliance in healthy
      humans. Ten healthy humans completed a 6-week randomized, double-blind, crossover
      trial of sertraline (50 mg day(-1)) vs. placebo. After each 2-week treatment,
      fullness, pain and nausea were rated at increasing gastric barostat distending
      pressures. Sensation thresholds above minimal distending pressure (MDP) were
      determined with a tracking method. Somatic sensory testing was performed by hand
      immersion in ice water. No differences were found between sertraline and placebo
      for symptoms as a function of distending pressure (fullness, P = 0.72; pain, P =
      0.79; nausea, P = 0.41), gastric compliance (P = 0.15), median and interquartile
      range thresholds for first sensation [4.1 (3.5-5.7) vs. 6.2 (3.3-10.0) mmHg above
      MDP, P = 0.19] and pain [15.2 (8.3-21.0) vs. 15.3 (10.3-19.8) mmHg above MDP, P =
      0.85], and median tolerance times for hand ice water immersion [27 (19-99) vs. 29
      (20-180) s, P = 0.73]. In conclusion, sertraline had no effect on gastric
      sensitivity or compliance, or somatic pain tolerance in healthy humans. Studies
      are needed to assess the effects of SSRIs on visceral sensation and clinical
      symptoms in patients with functional dyspepsia.

PMID- 12213108
TI  - Subdiaphragmatic vagal afferent innervation in activation of an opioidergic
      antinociceptive system in response to colorectal distension in rats.
AB  - Abstract In a number of different experimental paradigms of somatic pain, there
      is evidence for a vagally mediated antinociceptive system. This pathway probably
      involves opioid mechanisms. However, whether this pathway is activated in
      visceral pain or if it involves subdiaphragmatic vagal afferents is unclear. The
      aim of the present study was to determine whether subdiaphragmatic vagal
      afferents mediate antinociception in response to a visceral stimulus and whether
      this involves an opioid pathway. Colorectal distension was performed in fasted,
      conscious male Sprague-Dawley rats using a balloon catheter connected to an
      electronic distension device. The number of abdominal contractions (visceromotor
      response) in response to a tonic colorectal distension (60 mmHg for 10 min) was
      recorded. Experiments were performed in sham or subdiaphragmatically vagotomized,
      perineural vehicle- or capsaicin-treated rats (to functionally denervate vagal
      afferents) before and after administration of naloxone (25 mg kg(-1) bodyweight
      intraperitoneally). Vagotomy, capsaicin and naloxone pretreatments all
      significantly enhanced the visceromotor response to colorectal distension. The
      effect of naloxone in capsaicin-treated rats did not appear to be additive. These
      results suggest that activation of subdiaphragmatic afferents, which can be
      blocked by capsaicin, may play a role in opioid-dependent antinociceptive
      pathways activated by a noxious visceral stimulus.

PMID- 12213109
TI  - Clinical testing of gastrointestinal motor function: introduction and process.

PMID- 12213110
TI  - Manometry studies in children: minimum standards for procedures.

PMID- 12213111
TI  - Anthelmintic paraherquamides are cholinergic antagonists in gastrointestinal
      nematodes and mammals.
AB  - Oxindole alkaloids in the paraherquamide/marcfortine family exhibit broad
      spectrum anthelmintic activity that includes drug-resistant strains of nematodes.
      Paraherquamide (PHQ), 2-deoxoparaherquamide (2DPHQ), and close structural analogs
      of these compounds rapidly induce flaccid paralysis in parasitic nematodes in
      vitro, without affecting adenosine triphosphate (ATP) levels. The mechanism of
      action of this anthelmintic class was investigated using muscle tension and
      microelectrode recording techniques in isolated body wall segments of Ascaris
      suum. None of the compounds altered A. suum muscle tension or membrane potential.
      However, PHQ blocked (when applied before) or reversed (when applied after)
      depolarizing contractions induced by acetylcholine (ACh) and the nicotinic
      agonists levamisole and morantel. These effects were mimicked by the nicotinic
      ganglionic blocker mecamylamine, suggesting that the anthelmintic activity of PHQ
      and marcfortines is due to blockade of cholinergic neuromuscular transmission.
      The effects of these compounds were also examined on subtypes of human nicotinic
      ACh receptors expressed in mammalian cells with a Ca2+ flux assay. 2DPHQ blocked
      nicotinic stimulation of cells expressing alpha3 ganglionic (IC50 approximately 9
      microm) and muscle-type (IC50 approximately 3 microm) nicotinic cholinergic
      receptors, but was inactive at 100 microm vs. the alpha7 CNS subtype. PHQ
      anthelmintics are nicotinic cholinergic antagonists in both nematodes and
      mammals, and this mechanism appears to underlie both their efficacy and toxicity.

PMID- 12213112
TI  - Efficacy and pharmacokinetics of enrofloxacin and flunixin meglumine for
      treatment of cows with experimentally induced Escherichia coli mastitis.
AB  - The efficacy of flunixin alone and together with enrofloxacin in treatment of
      experimental Escherichia coli mastitis was compared using six cows. The cross
      over study design was used. Pharmacokinetics of flunixin and enrofloxacin were
      also studied in these diseased cows. The response of each cow was similar after
      the first and second challenge and the individual reaction seemed to explain the
      severity of clinical signs. The most important predictive factor for outcome of
      E. coli mastitis was a heavy drop in milk yield. Treatment with enrofloxacin and
      flunixin enhanced elimination of bacteria, but the difference from those
      receiving flunixin alone was not significant. Two cows, which had received no
      antimicrobial treatment (Group 1), were killed on day 4 postchallenge. One cow
      was killed after the first and the other after the second challenge. Cows
      receiving combination therapy produced 0.9 L more milk per day during the study
      period than cows which had only received flunixin (P < 0.05). Based on our
      findings, antimicrobial treatment might be beneficial in the treatment of high
      yielding cows in early lactation. The absorption of enrofloxacin was delayed
      after subcutaneous administration, the mean apparent elimination half-life being
      about 23 h, whereas after i.v. administration elimination t(1/2) was only 1.5 h.
      The majority of the antimicrobial activity in milk originated from the active
      metabolite, ciprofloxacin, which could be measured throughout the 120-h follow-up
      period after the last subcutaneous administration. No differences were present in
      the pharmacokinetic parameters of flunixin between treatment groups: mean
      elimination half-life was 5.7-6.2 h, volume of distribution 0.43-0.49 L/kg and
      clearance 0.13-0.14 L h/kg. No flunixin or merely traces were detected in milk:
      one of the three cows had a concentration of 0.019 mg/L 8 h after administration.

PMID- 12213113
TI  - Pharmacokinetics of an ampicillin/sulbactam (2:1) combination in rabbits.
AB  - The pharmacokinetics of a 2:1 ampicillin-sulbactam combination in six rabbits,
      after intravenous and intramuscular injection at a single dosage of 20 mg/kg
      bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam)
      were investigated by using a high performance liquid chromatographic method for
      determining plasma concentrations. The plasma concentration-time curves were
      analysed by compartmental pharmacokinetic and noncompartmental methods. The
      disposition curves for both drugs were best described by an open two-compartment
      model after intravenous administration and a one-compartment model with first
      order absorption after intramuscular administration. The apparent volumes of
      distribution calculated by the area method for ampicillin and sulbactam were 0.62
      +/- 0.09 and 0.45 +/- 0.05 L/kg, respectively, and the total body clearances were
      0.65 +/- 0.04 and 0.42 +/- 0.05 L/kg h, respectively. The elimination half-lives
      of ampicillin after intravenous and intramuscular administration were 0.64 +/-
      0.11 and 0.63 +/- 0.16 h, respectively, whereas for sulbactam the half-lives were
      0.74 +/- 0.12 and 0.77 +/- 0.17 h, respectively. The bioavailability after
      intramuscular injection was high and similar in both drugs (73.34 +/- 10.08% for
      ampicillin and 83.20 +/- 7.41% for sulbactam). The mean peak plasma
      concentrations of ampicillin and sulbactam were reached at similar times (0.20 +/
      0.09 and 0.34 +/- 0.15 h, respectively) and peak concentrations were also
      similar but nonproportional to the dose of both products administered (13.07 +/-
      3.64 mg/L of ampicillin and 8.42 +/- 1.74 mg/L of sulbactam). Both drugs had
      similar pharmacokinetic behaviour after intramuscular administration in rabbits.

PMID- 12213114
TI  - Pharmacokinetics of selamectin following intravenous, oral and topical
      administration in cats and dogs.
AB  - The pharmacokinetics of selamectin were evaluated in cats and dogs, following
      intravenous (0.05, 0.1 and 0.2 mg/kg), topical (24 mg/kg) and oral (24 mg/kg)
      administration. Following selamectin administration, serial blood samples were
      collected and plasma concentrations were determined by high performance liquid
      chromatography (HPLC). After intravenous administration of selamectin to cats and
      dogs, the mean maximum plasma concentrations and area under the concentration
      time curve (AUC) were linearly related to the dose, and mean systemic clearance
      (Clb) and steady-state volume of distribution (Vd(ss)) were independent of dose.
      Plasma concentrations after intravenous administration declined polyexponentially
      in cats and biphasically in dogs, with mean terminal phase half-lives (t(1/2)) of
      approximately 69 h in cats and 14 h in dogs. In cats, overall Clb was 0.470 +/-
      0.039 mL/min/kg (+/-SD) and overall Vd(ss) was 2.19 +/- 0.05 L/kg, compared with
      values of 1.18 +/- 0.31 mL/min/kg and 1.24 +/- 0.26 L/kg, respectively, in dogs.
      After topical administration, the mean C(max) in cats was 5513 +/- 2173 ng/mL
      reached at a time (T(max)) of 15 +/- 12 h postadministration; in dogs, C(max) was
      86.5 +/- 34.0 ng/mL at T(max) of 72 +/- 48 h. Bioavailability was 74% in cats and
      4.4% in dogs. Following oral administration to cats, mean C(max) was 11,929 +/-
      5922 ng/mL at T(max) of 7 +/- 6 h and bioavailability was 109%. In dogs, mean
      C(max) was 7630 +/- 3140 ng/mL at T(max) of 8 +/- 5 h and bioavailability was
      62%. There were no selamectin-related adverse effects and no sex differences in
      pharmacokinetic parameters. Linearity was established in cats and dogs for plasma
      concentrations up to 874 and 636 ng/mL, respectively. Pharmacokinetic evaluations
      for selamectin following intravenous administration indicated a slower
      elimination from the central compartment in cats than in dogs. This was reflected
      in slower clearance and longer t(1/2) in cats, probably as a result of species
      related differences in metabolism and excretion. Inter-species differences in
      pharmacokinetic profiles were also observed following topical administration
      where differences in transdermal flux rates may have contributed to the overall
      differences in systemic bioavailability.

PMID- 12213115
TI  - Distribution of orally administered trimethoprim and sulfadiazine into
      noninfected subcutaneous tissue chambers in adult ponies.
AB  - The distribution of trimethoprim (TMP) and sulfadiazine (SDZ) into subcutaneously
      implanted noninfected tissue chambers was studied in healthy adult ponies. Six
      ponies were given an oral TMP/SDZ paste formulation at a dose of 5 mg/kg TMP and
      25 mg/kg SDZ at 12 h intervals for 2 days in order to reach steady-state
      concentrations. Plasma concentrations and tissue chamber fluid (TCF)
      concentrations of both drugs were measured at regular intervals during a period
      commencing 24 h after the last oral administration. The peak concentration of TMP
      (mean +/- SD) was 2.92 +/- 0.86 microg/mL for plasma and 1.09 +/- 0.25 microg/mL
      for TCF. For SDZ, the mean peak concentration was 40.20 +/- 14.74 microg/mL for
      plasma and 23.48 +/- 5.84 microg/mL for TCF. TMP peak concentrations in plasma
      were reached at 3.17 +/- 03.48 h and those in TCF at 7.33 +/- 03.72 h. SDZ peak
      concentrations in plasma were reached at 1.83 +/- 02.04 h and those in TCF at
      8.00 +/- 03.10 h. Concentrations of TMP and SDZ in TCF remained above the
      generally accepted breakpoint for susceptibility (0.5/9.5 for the TMP/SDZ
      combination) for 12 h. Therefore, in ponies oral administration of TMP/SDZ at a
      dose rate of 30 mg/kg given twice daily in the form of a paste should be
      appropriate for effective treatment of infections caused by susceptible bacteria.

PMID- 12213116
TI  - The effect of josamycine on the control of ileitis in weaned piglets under field
      conditions.
AB  - The aim of this trial was to evaluate the effect of in-feed josamycine on the
      control of ileitis in weaned piglets. On a farm with a previous history of
      ileitis outbreaks, 288 piglets at weaning age (25 +/- 2 days old) were allocated
      into three experimental groups, each group comprising of four pens with 24
      piglets in each pen. Group one (T1) served the trial as negative control group
      (unmedicated), group T2 was administered josamycine at 36 mg/kg of feed and group
      T3 was administered josamycine at 50 mg/kg of feed. Treatments lasted for 14 days
      followed by an observation period of 28 days. Administration of josamycine at
      both inclusion levels tested had a beneficial effect compared with the negative
      control group, by the reduction of prevalence of diarrhoea, the enhancement of
      growth performance and the reduction of prevalence of Lawsonia intracellularis in
      the intestine, as determined either by the PCR method or by specific
      histopathological examinations. The beneficial effect of josamycine was more
      pronounced at the inclusion level of 50 mg/kg of feed.

PMID- 12213117
TI  - Lack of daily rhythms major modifications despite continuous infusion of
      melatonin in the rat.
AB  - The present study was conducted to evaluate the effect of melatonin on the daily
      rhythms of temperature, heart rate and locomotor activity in rats that received
      subcutaneously a continuous infusion of two different doses e.g. 1 and 5 mg/kg
      per day for seven days. Our results indicate that melatonin does not induce a
      loss of the daily rhythmicity of temperature, heart rate and locomotor activity.
      Whatever the dose, melatonin slightly modifies the main parameters of these
      rhythms e.g. a decrease of the amplitude of the daily rhythms of temperature and
      heart rate and an increase of the mesor of temperature. Taking into account these
      results obtained after constant rate delivery in normal rats, we plan now to
      investigate the effects of melatonin on our experimental model of Parkinson's
      disease (double bilateral intrastriatal 6-hydroxydopamine injection).

PMID- 12213118
TI  - Effects of anti-arthritic drugs on proteoglycan synthesis by equine cartilage.
AB  - The concentration-effect relationships of phenylbutazone, indomethacin,
      betamethasone, pentosan polysulphate (PPS) and polysulphated glycosaminoglycan
      (PSGAG), on proteoglycan synthesis by equine cultured chondrocytes grown in
      monolayers, and articular cartilage explants were measured. The effect of PSGAG
      on interleukin-1beta induced suppression of proteogycan synthesis was also
      investigated. Proteoglycan synthesis was measured by scintillation assay of
      radiolabelled sulphate (35SO4) incorporation. Polysulphated glycosaminoglycan and
      PPS stimulated proteoglycan synthesis in chondrocyte monolayers in a
      concentration-related manner with maximal effects being achieved at a
      concentration of 10 microg/mL. Polysulphated glycosaminoglycan reversed the
      concentration-related suppression of proteoglycan synthesis induced by
      interleukin-1beta. Neither PSGAG nor PPS exerted significant effects on
      radiolabel incorporation in cartilage explants. Betamethasone suppressed
      proteoglycan synthesis by both chondrocytes and explants at high concentrations
      (0.1-100 microg/mL), but the effect was not concentration-related. At low
      concentrations (0.001-0.05 microg/mL) betamethasone neither increased nor
      decreased proteoglycan synthesis. Phenylbutazone and indomethacin increased
      radiolabel incorporation in chondrocyte cultures but not in cartilage explants at
      low (0.1, 1 and 10 microg/mL), but not at high (20 and 100 microg/mL)
      concentrations. These findings may be relevant to the clinical use of these drugs
      in the treatment of equine disease.

PMID- 12213119
TI  - Pharmacodynamics and pharmacokinetics of phenylbutazone in calves.
AB  - Phenylbutazone (PBZ) was administered to six calves intravenously (i.v.) and
      orally at a dose rate of 4.4 mg/kg in a three-period cross-over study
      incorporating a placebo treatment to establish its pharmacokinetic and
      pharmacodynamic properties. Extravascular distribution was determined by
      measuring penetration into tissue chamber fluid in the absence of stimulation
      (transudate) and after stimulation of chamber tissue with the mild irritant
      carrageenan (exudate). PBZ pharmacokinetics after i.v. dosage was characterized
      by slow clearance (1.29 mL/kg/h), long-terminal half-life (53.4 h), low
      distribution volume (0.09 L/kg) and low concentrations in plasma of the
      metabolite oxyphenbutazone (OPBZ), confirming previously published data for adult
      cattle. After oral dosage bioavailability (F) was 66%. Passage into exudate was
      slow and limited, and penetration into transudate was even slower and more
      limited; area under curve values for plasma, exudate and transudate after i.v.
      dosage were 3604, 1117 and 766 microg h/mL and corresponding values after oral
      dosage were 2435, 647 and 486 microg h/mL. These concentrations were
      approximately 15-20 (plasma) and nine (exudate) times greater than those
      previously reported in horses (receiving the same dose rate of PBZ). In the
      horse, the lower concentrations had produced marked inhibition of eicosanoid
      synthesis and suppressed the inflammatory response. The higher concentrations in
      calves were insufficient to inhibit significantly exudate prostaglandin E2
      (PGE2), leukotriene B4 (LTB4) and beta-glucuronidase concentrations and exudate
      leucocyte numbers, serum thromboxane B2 (TxB2), and bradykinin-induced skin
      swelling. These differences from the horse might be the result of: (a) the
      presence in equine biological fluids of higher concentrations than in calves of
      the active PBZ metabolite, OPBZ; (b) a greater degree of binding of PBZ to plasma
      protein in calves; (c) species differences in the sensitivity to PBZ of the cyclo
      oxygenase (COX) isoenzymes, COX-1 and COX-2 or; (d) a combination of these
      factors. To achieve clinical efficacy with single doses of PBZ in calves, higher
      dosages than 4.4 mg/kg will be probably required.

PMID- 12213120
TI  - The effects of hydrogen peroxide on the stress response of Atlantic Salmon (Salmo
      salar).

PMID- 12213121
TI  - Disposition of oxytetracycline in pigs after i.m. administration of two long
      acting formulations.

PMID- 12213123
TI  - Novel peptide inhibitors for Grb2 SH2 domain and their detection by surface
      plasmon resonance.
AB  - One of the critical intracellular signal transduction pathways involves the
      binding of the Grb2 SH2 domain to the phosphotyrosine (pTyr) motifs on growth
      factor receptors, such as epidermal growth factor receptor (EGFR) and erbB2,
      leading to downstream activation of the oncogenic Ras signaling pathway.
      Therefore, the Grb2 SH2 domain has been chosen as our target for the development
      of potential anticancer agents. As a continuation of our earlier work, herein we
      report the design and synthesis of new peptide analogs, and their inhibitory
      effect on the Grb2 SH2 domain using surface plasmon resonance (SPR) technology.
      These novel agents do not contain phosphotyrosine or phosphotyrosine mimics.
      Binding interactions between these peptides and the Grb2 SH2 domain were measured
      and analyzed using a BIAcore X instrument, which provides detailed information on
      the real-time detection of the binding interaction. The results of this study
      should provide important information for the further development of peptides or
      peptidomimetics with high affinity for the Grb2 SH2 domain.

PMID- 12213124
TI  - Synthetic peptide epitope-based polymers: controlling size and determining the
      efficiency of epitope incorporation.
AB  - The assembly of synthetic peptide-based vaccines that incorporate multiple
      epitopes is a major goal of vaccine development, because such vaccines will
      potentially allow the immunization of outbred populations against a number of
      different pathogens. We have shown that free radical-induced polymerization of
      individual peptide epitopes results in the incorporation of multiple copies of
      the same or different epitopes into high molecular weight immunogens (O'Brien
      Simpson, N.M., Ede, N.J., Brown, L.E., Swan, J. & Jackson, D.C. (1997)
      Polymerization of unprotected synthetic peptides: a view toward synthetic peptide
      vaccines. J. Am. Chem. Soc.119, 1183-1188; Jackson, D.C., O'Brien-Simpson, N.,
      Ede, N.J. & Brown, L.E. (1997) Free radical induced polymerization of synthetic
      peptides into polymeric immunogens. Vaccine 15, 1697-1705). The ability to
      control the size of these polymers, to determine the physical and chemical
      properties of the backbone material and also to know the extent to which
      individual peptide epitopes are incorporated are important manufacturing
      considerations and form the subject of this study. We show here that the
      polymerization process is highly efficient with at least 70% of peptides
      incorporated into the resulting polymer, that acrylamide and acryloylated amino
      acids can be used as comonomers with peptide epitopes in the polymerization
      reaction and that the choice of the comonomer can influence the properties of the
      resulting polymer. We also show that the size of chain growth polymers is
      restricted in the presence of chain transfer agents, that the resulting polymer
      size can be predicted and that there is little or no difference in the
      immunogenicity of polymers that range in apparent molecular size between 18 kDa
      and 335 kDa. The successful polymerization of peptide epitopes with an acryloyl
      amino acid creates the potential for introducing different physical and chemical
      properties into artificial protein immunogens.

PMID- 12213125
TI  - Characterization of the solution conformations of leuprolide acetate.
AB  - Leuprolide acetate (pGlu-His-Trp-Ser-Tyr-d-Leu-Leu-Arg-Pro-NHEt), a potent LHRH
      agonist in wide clinical use, was characterized conformationally by NMR and
      circular dichroism. It displayed quite different preferred conformations under
      different solution conditions: two low population beta-turns in water, a nascent
      helix in TFE/water at low pH, and a high population beta-turn in TFE/water at
      slightly acidic pH. The pH-related conformational change in TFE/water is
      attributed to the pK(a) of the acetate counterion, not to ionizable groups on the
      peptide. None of these conformations are in exact agreement with previous
      computational predictions.

PMID- 12213126
TI  - The cytoplasmic helix of cannabinoid receptor CB2, a conformational study by
      circular dichroism and (1)H NMR spectroscopy in aqueous and membrane-like
      environments.
AB  - The cytoplasmic helix domain (fourth cytoplasmic loop, helix 8) of numerous G
      protein-coupled receptors (GPCRs) such as rhodopsin and the beta-adrenergic
      receptor exhibit unique structural and functional characteristics. Computer
      models also predict this structure for the cannabinoid CB2 receptor, another
      member of the GPCR superfamily. In our study, a peptide corresponding to helix 8
      of the CB2 receptor was synthesized chemically and its secondary structure
      determined by circular dichroism (CD) and (1)H NMR spectroscopy. NMR and CD
      revealed an alpha-helical structure in this region in both dodecylphosphocholine
      micelles and dimethylsulfoxide, in contrast to a random coil configuration found
      in aqueous solvent. This finding is in good agreement with other previous GPCR
      structural studies including X-ray crystallography. By combining our finding with
      other studies, we further hypothesize that the amphipathic nature of helix 8 can
      play a significant role in the function and regulation of CB receptors as well as
      other GPCRs in general.

PMID- 12213127
TI  - Multiple anchoring of myelopeptides on sequential oligopeptide carriers (SOC(n)):
      synthesis, conformation and studies in human leukemia cells.
AB  - Myelopeptides, MP-6 (Val-Asp-Pro-Pro) and MP-4 (Phe-Arg-Pro-Arg-Ile-Met-Thr-Pro),
      induce metabolic changes in human leukemia cells, HL-60, characteristic of the
      differentiation process, which should be regarded as a promising therapeutic
      approach in cancer and related diseases. With the aim to optimize the
      differentiation effect of MPs, they were coupled to the Lys-N(epsilon)H(2) groups
      of a sequential oligopeptide carrier Ac-(Lys-Aib-Gly)(4), SOC(4), and the
      constructs obtained were studied. The rigid 3(10) secondary structure of the
      carrier is preserved even after linkage of the MPs, which also maintain their
      initial conformations without interacting either with each other or with the
      carrier, as demonstrated by (1)H nuclear magnetic resonance (NMR) spectroscopy.
      It is concluded that the carrier accommodates the presentation of MPs, thus
      improving their differentiation effect on human leukemia cells.

PMID- 12213128
TI  - Editorial: in praise of blind poets.

PMID- 12213129
TI  - Vasoactive intestinal polypeptide contacts on gonadotropin-releasing hormone
      neurones increase following puberty in female rats.
AB  - Successful reproduction requires precise temporal coordination among various
      endocrine and behavioural events. The circadian system regulates daily temporal
      organization in behaviour and physiology, including neuroendocrine rhythms. The
      main circadian pacemaker in mammals is located in the suprachiasmatic nuclei
      (SCN) of the anterior hypothalamus. The SCN sends direct efferents to the
      reproductive axis via monosynaptic projections to gonadotropin-releasing hormone
      (GnRH) neurones. This communication generates circadian endocrine rhythms as well
      as the preovulatory luteinizing hormone (LH) surge necessary for successful
      ovulation. One SCN peptide thought to be important for the regulation of oestrous
      cycles is vasoactive intestinal polypeptide (VIP). VIP neurones from the SCN
      contact GnRH cells, and these cells are preferentially activated during an LH
      surge in rats. Unlike adult rats, prepubertal females do not exhibit oestrous
      cycles, nor do they exhibit an LH surge in response to oestradiol positive
      feedback. The present study was undertaken to determine the extent to which the
      development of a 'mature' reproductive axis in female rats is associated with
      modifications in VIP contacts on GnRH neurones. The brains of diestrus adult
      (approximately 60 days of age) and prepubertal (21 days of age) female rats were
      examined using double-label fluorescence immunohistochemistry for VIP and GnRH,
      with light and confocal microscopy. Although the total number of GnRH
      immunoreactive neurones did not differ between adult and prepubertal females,
      adults had a significant increase in the percentage of GnRH cells receiving VIP
      contacts compared to juveniles. These data suggest that the development of
      reproductive hormone rhythms and oestrous cyclicity may be, in part, due to
      modifications of VIP input to the GnRH system.

PMID- 12213130
TI  - Physiological concentrations of melatonin and corticosterone in stress and their
      relationship with phagocytic activity.
AB  - The aim of the present work was to investigate the possible connection between
      melatonin, corticosterone and the nonspecific immune response under both basal
      and stressed conditions. The concentrations used in the present study were as
      determined in an earlier work, and corresponded to the minimum and maximum
      concentrations of the hormones melatonin and corticosterone over one circadian
      cycle in mice subjected to stress and in a basal group of mice. The
      concentrations were 15 pg/ml and 90 pg/ml of melatonin and 50 ng/ml and 200 ng/ml
      of corticosterone for incubations of the basal group macrophages, and 15 pg/ml
      and 70 pg/ml and 200 ng/ml and 500 ng/ml of melatonin and corticosterone,
      respectively, for incubations of macrophages from the group of stressed mice. The
      results indicate that corticosterone stimulates antigen ingestion at all
      physiological doses tested in the macrophages from the unstressed mice. The
      greatest phagocytic stimulation was obtained in macrophages from mice in a basal
      situation, and which had been incubated with the diurnal concentrations of the
      two hormones (maximum corticosterone 200 ng/ml; minimum melatonin 15 pg/ml). When
      the macrophages were from stressed mice, neither corticosterone nor melatonin led
      to any change in their phagocytic activity.

PMID- 12213131
TI  - Cocaine and amphetamine-regulated transcript mRNA regulation in the hypothalamus
      in lean and obese rodents.
AB  - Cocaine and amphetamine-regulated transcript (CART) mRNA and immunoreactivity are
      expressed abundantly in the hypothalamus. Central administration of various
      fragments of this neuropeptide decreases food intake in rodents. To find out
      whether CART might play a role in the physiological regulation of energy balance,
      we used in situ hybridization to investigate whether CART mRNA abundance changed
      in two chronic obese/fat versus lean states and after acute dietary restriction.
      In the first study, mice were treated with goldthioglucose to destroy glucose
      responsive neurones in the ventromedial hypothalamus. This produced hyperphagia
      and obesity: 7 weeks after treatment, those receiving goldthioglucose weighed 70%
      more than the controls. CART mRNA abundance in the arcuate nucleus of
      goldthioglucose-treated mice was decreased by 71% compared to levels in the
      control mice, but CART expression was unaffected in the dorsolateral
      hypothalamus. In the second study, male Siberian hamsters were exposed to short
      days to induce a physiological winter response in which body weight decreases as
      fat reserves are catabolized, and food intake correspondingly declines. After 8
      weeks in short days, body weight had declined by 18% relative to controls
      maintained in long days in a summer fat state. CART mRNA levels did not differ
      significantly between the two groups in any hypothalamic areas. In the third
      study, male Siberian hamsters, either in long days or after 12 weeks exposure to
      short days to induce weight loss, were subject to a 48-h period of fasting.
      Although photoperiod per se did not affect CART expression, fasting produced a
      significant decrease in CART mRNA in the arcuate nucleus of hamsters in both the
      long- and short-day state. We conclude that CART-producing cells are involved in
      energy homeostasis: the marked decrease in CART expression in the arcuate nucleus
      in goldthioglucose-lesioned mice may contribute to the development of obesity,
      and the decrease following acute dietary restriction in hamsters may reflect a
      compensatory mechanism to reduce caloric expenditure, but our results do not
      indicate that CART is involved in long-term seasonal regulation of body weight.

PMID- 12213132
TI  - Prostaglandin F2alpha-induced nest-building behaviour is associated with
      increased hypothalamic c-fos and c-jun mRNA expression.
AB  - Intramuscular injection of the naturally occurring prostaglandin F2alpha
      (PGF2alpha) to sexually mature female pigs induces luteolysis and rapidly elicits
      a behavioural response consistent with pre-partum nest-building. Intramuscular
      injection of the synthetic prostaglandin F2alpha (cloprostenol) also induces
      luteolysis but no nest-building behaviour is observed. The effects of PGF2alpha,
      but not cloprostenol, on nest-building behaviour may be mediated via peripheral
      PGF2alpha receptors (FP) or via direct action on central FP receptors. We have
      previously shown FP receptor mRNA to be localized in porcine paraventricular
      nucleus (PVN), supraoptic nucleus (SON) and pars dorso-medialis of the suproptic
      nucleus (SOD), suprachiasmatic nucleus, choroid plexus and anterior and
      intermediate pituitary lobes. In this experiment, we examined hypothalamic
      expression of the immediate early genes c-fos and c-jun mRNA after treatment with
      PGF2alpha or cloprostenol. Twenty-one 8-month-old nulliparous female pigs (gilts)
      were injected intramuscularly with a luteolytic dose of PGF2alpha (15 mg),
      cloprostenol (175 microg) or saline control, their behaviour was recorded and
      they were killed 60 min later. Coronal hypothalamic sections and control ovarian
      tissues were incubated with 45-mer oligonucleotide probes complementary to
      porcine c-fos and c-jun genes using standard in situ hybridization histochemistry
      techniques. Significantly higher c-fos and c-jun mRNA expression was found in
      PGF2alpha-treated compared to saline or cloprostenol-treated pigs in the PVN, SON
      and SOD. Significantly higher c-fos and c-jun mRNA expression was found in corpus
      lutea of PGF2alphaand cloprostenol-treated pigs compared to saline controls.
      Treatment with PGF2alpha induced nest-building behaviour whereas treatment with
      cloprostenol and saline did not. This suggests that PGF2alpha, or one of its
      metabolites, and not cloprostenol, crosses the blood-brain barrier and acts
      directly on hypothalamic receptors to mediate its effect on nest-building
      behaviour.

PMID- 12213133
TI  - Hypothalamic interactions between neuropeptide Y, agouti-related protein, cocaine
      and amphetamine-regulated transcript and alpha-melanocyte-stimulating hormone in
      vitro in male rats.
AB  - A number of neuropeptides implicated in the hypothalamic regulation of appetite
      are synthesized in the arcuate nucleus (Arc). Neuropeptide Y (NPY) and agouti
      related protein (Agrp) are orexigenic. The pro-opiomelanocortin (POMC) product
      alpha-melanocyte-stimulating hormone (alpha-MSH) is anorectic.
      Intracerebroventricular administration of cocaine- and amphetamine-regulated
      transcript (CART) decreases food intake. However, recent results show that CART
      is orexigenic when injected into discrete hypothalamic nuclei. There is almost
      complete coexpression of NPY and Agrp mRNA in Arc neurones, and the majority of
      CART-containing neurones in the Arc also contain POMC mRNA. We investigated
      possible interactions between these neuropeptides in vitro using a rat
      hypothalamic explant system. Administration of 1, 10 and 100 nm of NPY to
      hypothalamic explants significantly increased release of Agrp(83-132)
      immunoreactivity (IR). NPY (10 and 100 nm) significantly increased the release of
      CART(55-102)-IR and alpha-MSH-IR from hypothalamic explants. Agrp(83-132) (10 nm)
      administered to hypothalamic explants significantly increased the release of NPY
      IR. Agrp(83-132) (10 and 100 nm) significantly decreased the release of CART(55
      102)-IR from hypothalamic explants. Administration of 1, 10 and 100 nm CART(55
      102) to hypothalamic explants resulted in a significant increase in NPY-IR
      release. Administration of 10 nm CART(55-102) to hypothalamic explants
      significantly increased the release of Agrp(83-132)-IR. NDP-MSH (10 nm)
      administered to hypothalamic explants significantly increased the release of NPY
      IR. NDP-MSH (10 and 100 nm) significantly increased the release of Agrp(83-132)
      IR from hypothalamic explants. These data suggest that orexigenic neuropeptides
      in the arcuate nucleus stimulate the release of each other, perhaps reinforcing
      orexigenic behaviour via a positive-feedback loop. Our results are also in
      keeping with the possibility that the melanocortin-3 receptor in the arcuate
      nucleus may influence the release of arcuate neuropeptides.

PMID- 12213135
TI  - Overexpression of the V3 vasopressin receptor in transgenic mice corticotropes
      leads to increased basal corticosterone.
AB  - The vasopressin V3 receptor (V3) is specifically expressed in pituitary
      corticotropes and mediates the stimulatory effect of vasopressin on
      adrenocorticotropic hormone (ACTH) release. The V3 gene is overexpressed in
      corticotrope pituitary tumours compared to normal pituitaries. We hypothesized
      that V3 overexpression might induce changes in corticotrope function and alter
      the regulation of the hypothalamic-pituitary-adrenal axis. Thus, we generated
      transgenic mice (POMV3) expressing the human V3 receptor in the pituitary under
      the control of rat pro-opiomelanocortin (POMC) promoter sequences. The transgene
      was efficiently transcribed and vasopressin binding was increased in both
      corticotropes and melanotropes. In-vitro ACTH release and inositol phosphate
      formation were unchanged in POMV3 pituitaries, but the responses to vasopressin
      were significatively increased. In vivo, basal circulating concentrations of ACTH
      in POMV3 mice were similar to those of controls but corticosterone concentrations
      were moderately increased. In addition, the levels of POMC mRNA in the transgenic
      pituitaries were comparable to those of control mice. Finally, POMV3 mice
      responded with a similar maximal increase of ACTH and corticosterone to a 20-min
      acute restraint stress. Together, these results show that hypophyseal V3
      overexpression led to increased basal concentrations of corticosterone and
      suggest that the negative glucocorticoid feedback may be altered at the pituitary
      level.

PMID- 12213134
TI  - Lack of effect of testosterone and dihydrotestosterone compared to 17beta
      oestradiol in 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine-mice.
AB  - Previous work from our laboratory has demonstrated prevention of 1-methyl-4
      phenyl-1,2,3,6, tetrahydropyridine (MPTP)-induced striatal dopamine depletion in
      C57Bl/6 mice by 17beta-oestradiol, progesterone and raloxifene. The activity of
      androgenic compounds in MPTP mice has received less attention and was the object
      of the present investigation. The effects of 17beta-oestradiol (2 microg/day),
      testosterone (100 microg/day) and dihydrotestosterone (DHT) (2 microg/day or 100
      microg/day) were studied during 5 days before and after an acute treatment of
      four MPTP (10 mg/kg) injections in male C57Bl/6 mice. Striatal concentrations of
      dopamine and its metabolites dihydroxyphenylacetic acid and homovanillic acid
      were measured by high-performance liquid chromatography. MPTP mice treated with
      saline showed large decreases in dopamine and its metabolites compared to control
      mice. 17beta-oestradiol partially spared this decrease whereas testosterone and
      DHT did not. Striatal specific binding to the dopamine transporter (DAT) and to
      the vesicular monoamine transporter (VMAT2) were measured using [125I] RTI-121
      and [3H] dihydrotetrabenazine autoradiography, respectively. As with striatal
      dopamine concentrations, MPTP treatment caused a decrease in DAT and VMAT2
      specific binding. 17beta-oestradiol partially spared this decrease, whereas
      androgens did not. In the substantia nigra, DAT mRNA was measured by in situ
      hybridization. MPTP treatment induced a significant, but smaller decrease in
      substantia nigra DAT mRNA than striatal DAT protein. In addition, 17beta
      oestradiol completely prevented the MPTP-induced decrease of DAT mRNA, whereas
      androgens did not. The present results show that androgens are unable to protect
      against MPTP-induced dopaminergic toxicity.

PMID- 12213136
TI  - Fasting stimulates tuberoinfundibular dopaminergic neuronal activity and inhibits
      prolactin secretion in oestrogen-primed ovariectomized rats: involvement of
      orexin A and neuropeptide Y.
AB  - Fasting up-regulates central orexigenic systems including orexin A and
      neuropeptide Y (NPY) and it also inhibits the secretion of prolactin. We
      hypothesized that fasting may act through orexin A and NPY to influence
      tuberoinfundibular dopaminergic (TIDA) neurones, the major regulator of prolactin
      secretion. The effects of orexin A and NPY on TIDA neuronal activity and
      prolactin secretion were determined in oestrogen-primed ovariectomized rats, and
      the effects of fasting and the involvement of orexin A and NPY were tested.
      Orexin A, NPY and its analogs were administered through preimplanted
      intracerebroventricular (i.c.v.) cannulae. TIDA neuronal activity was determined
      by measuring concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) or 3,4
      dihydroxyphenylalanine in the median eminence. i.c.v. injection of NPY (10
      microg) or orexin A (1 microg) concomitantly increased median eminence DOPAC and
      decreased serum prolactin concentrations. The effect of NPY was mimicked by a Y1
      receptor agonist at lower doses (0.1 and 1 microg) and no additive effect was
      observed when orexin A and the Y1 agaonist were coadministered. Moreover, a Y1
      receptor antagonist, BIBP, not only blocked the effect of Y1 agaonist, but also
      that of orexin A. Treatment with BIBP alone decreased median eminence DOPAC and
      increased serum prolactin concentrations, indicating that endogenous NPY may play
      a role. Moreover, fasting for 48 h significantly increased TIDA neuronal
      activity, both in the morning and afternoon, and the effect was reversed by
      treatment with either BIBP or an antibody against orexin A. The findings support
      our hypothesis that fasting stimulates TIDA neuronal activity and inhibits
      prolactin secretion through up-regulated central orexin A and NPY systems.

PMID- 12213137
TI  - Penetration of endogenous steroid hormones corticosterone, cortisol, aldosterone
      and progesterone into the brain is enhanced in mice deficient for both mdr1a and
      mdr1b P-glycoproteins.
AB  - Numerous investigations have confirmed an important role for multidrug-resistance
      gene 1-type P-glycoproteins (MDR1-type P-gps) in the blood-brain barrier,
      protecting the brain against the accumulation of a wide range of toxic
      xenobiotics and drugs. Several studies have provided evidence in vitro that
      certain steroid hormones are transported by MDR1-type P-gps; however, the
      question of whether this might also apply to the situation in vivo still remained
      to be determined. We used mice deficient for both murine mdr1a and mdr1b P-gps
      [mdr1a/1b(-/-)] to determine the uptake of [3H]-cortisol, [3H]-corticosterone,
      [3H]-aldosterone and [3H]-progesterone into the plasma, brain, testes, liver,
      spleen, pituitary and adrenal glands. We provide evidence that the access of the
      endogenous steroid hormones corticosterone, cortisol and aldosterone is regulated
      by MDR1-type P-gps in vivo. As peripherally administered steroid hormones
      accumulate in the brain of mice deficient for MDR1-type P-gps, mdr1a/1b proteins
      are likely to transport these hormones out of the brain, providing a kinetic
      barrier to their entry. Intracerebral progesterone concentrations are influenced
      by MDR1-type P-gp function as well; however, the effects are only small. In
      addition, all four endogenous glucocorticoid hormones accumulated in the testes
      of mdr1a/1b(-/-) mice. Our findings underline the importance of MDR1-type P-gps
      as an endogenous barrier system controlling the access of endogenous steroid
      hormones at the blood-brain barrier to maintain homeostatic control and to
      protect central nervous system neurones.

PMID- 12213138
TI  - Prescribing errors involving medication dosage forms.
AB  - CONTEXT: Prescribing errors involving medication dose formulations have been
      reported to occur frequently in hospitals. No systematic evaluations of the
      characteristics of errors related to medication dosage formulation have been
      performed. OBJECTIVE: To quantify the characteristics, frequency, and potential
      adverse patient effects of prescribing errors involving medication dosage forms.
      DESIGN: Evaluation of all detected medication prescribing errors involving or
      related to medication dosage forms in a 631-bed tertiary care teaching hospital.
      MAIN OUTCOME MEASURES: Type, frequency, and potential for adverse effects of
      prescribing errors involving or related to medication dosage forms. RESULTS: A
      total of 1,115 clinically significant prescribing errors involving medication
      dosage forms were detected during the 60-month study period. The annual number of
      detected errors increased throughout the study period. Detailed analysis of the
      402 errors detected during the last 16 months of the study demonstrated the most
      common errors to be: failure to specify controlled release formulation (total of
      280 cases; 69.7%) both when prescribing using the brand name (148 cases; 36.8%)
      and when prescribing using the generic name (132 cases; 32.8%); and prescribing
      controlled delivery formulations to be administered per tube (48 cases; 11.9%).
      The potential for adverse patient outcome was rated as potentially "fatal or
      severe" in 3 cases (0.7%), and "serious" in 49 cases (12.2%). Errors most
      commonly involved cardiovascular agents (208 cases; 51.7%). CONCLUSIONS:
      Hospitalized patients are at risk for adverse outcomes due to prescribing errors
      related to inappropriate use of medication dosage forms. This information should
      be considered in the development of strategies to prevent adverse patient
      outcomes resulting from such errors.

PMID- 12213140
TI  - Referral sources to a weight management program: relation to outcome.
AB  - OBJECTIVE: To examine the characteristics and outcomes of physician-referred
      weight management patients relative to self-referred patients. DESIGN: Review of
      clinic records of all individuals contacting a weight control program during a 2
      year period with follow-up throughout consecutive levels of treatment (i.e.,
      enrollment, completion, and outcome). SETTING: Medical school weight management
      center. PARTICIPANTS: A consecutive sample (N = 1,392) of overweight and obese
      callers was categorized as physician-initiated (n = 345), media (n = 653), or
      personal (n = 394) referrals. Attendees at initial consultation (n = 571) were
      age 41.7 +/- 12.8 years, weight 113.9 +/- 36.1 kilograms, and body mass index
      (BMI) 40.3 +/- 11.3 kg/m(2) (data expressed as mean +/- standard deviation).
      INTERVENTIONS: Low-calorie-diet and very-low-calorie-diet programs. MAIN OUTCOME
      MEASURES: Gender comparisons, attendance at initial consultation, body mass
      index, motivation, comorbidities, enrollment and completion rates, and weight
      loss. RESULTS: Compared to callers from other referral sources, physician
      referrals included a larger minority of males (25.2%) and were more likely to
      attend an initial consultation (63.5%; P < .001). Among consultation attendees,
      physician referrals were heavier (mean BMI = 44.8), reported more comorbidities,
      were less likely to join programs (16.9%), and scored as less motivated than
      other referrals (P < .007). Completion rates for physician referrals were higher
      than for self-referrals in the very-low-calorie-diet program (85.7%; P < .04) but
      not in the low-calorie-diet program (P > .05). Among completers, physician
      referrals did not differ on weight loss in either program (P > .05). CONCLUSIONS:
      Compared to self-referrals, physician-referred individuals are in greater need of
      weight loss, less motivated, less likely to enter treatment, but equally likely
      to profit from it. Therefore, physician referral for weight loss is beneficial
      for at least some patients and should be encouraged.

PMID- 12213139
TI  - Preventive health care measures before and after start of renal replacement
      therapy.
AB  - OBJECTIVE: To describe utilization of preventive health care measures in patients
      with chronic kidney disease (CKD), both in the year prior to onset of renal
      replacement therapy (RRT), and in the first year of RRT. METHODS: We identified a
      large cohort of patients with CKD in the New Jersey Medicaid and Medicare
      programs with fixed enrollment into the cohort at 1 year prior to RRT. We applied
      commonly used quality assurance instruments (Health Plan Employer Data and
      Information Set measures) and defined levels and correlates of use of preventive
      care measures before and after RRT. These included mammography, Pap smear
      testing, prostate cancer screening, diabetic eye exams, and glycosylated
      hemoglobin testing (HbA1c). We employed logistic regression models with
      adjustment for age, race, gender, comorbidity, timing of first nephrologist
      contact, socioeconomic status, and calendar year of first RRT. RESULTS: Overall,
      screening rates were low with the exception of diabetic eye exams. Prostate
      cancer screening, diabetic eye exams, and HbA1c testing were performed less often
      after onset of RRT compared to the year before (P < .05). Although screening
      rates before RRT improved considerably over the period of observation for these
      measures (P < .05), this was not the case once patients were on RRT. CONCLUSIONS:
      Preventive health care interventions remain underutilized among RRT patients.
      Greater attention to such preventive measures could lead to significant
      improvements in the health status of such vulnerable patients. Thus, quality
      improvement of the general health care for patients on RRT should become a
      priority in renal health policy.

PMID- 12213142
TI  - Presenting risks and benefits to patients.
AB  - OBJECTIVE: To investigate whether patients are influenced by the order in which
      they learn the risks and benefits of a treatment and whether this effect is
      attenuated by a treatment's associated risk and/or benefit. DESIGN: Subjects were
      randomized to review 1 of 6 medical treatment information brochures. SETTING:
      Waiting rooms of primary care physicians at an academic health center.
      PARTICIPANTS: Six hundred eighty-five subjects, ages 18 to 70 years.
      INTERVENTION: Subjects reviewed 1 of 3 treatments for symptomatic carotid artery
      disease. The first (aspirin) was low-risk/low-benefit, the second (carotid
      endarterectomy surgery) was high-risk/high-benefit, and the third (extracranial
      to-intracranial bypass surgery) was high-risk but of unknown benefit. Patients
      were also randomized to receive information about risk either before or after
      benefit. Patients were asked to rate the favorability of the treatment on a scale
      of 0 to 100 and whether they would consent. Finally, subjects rated how their
      decisions were influenced by the risk and benefit information. MAIN RESULTS:
      Subjects evaluating aspirin therapy were influenced by the order of the
      risk/benefit information. Those learning about risks after benefits had a greater
      drop in their favorability ratings than subjects learning about risks before
      benefits (-10.9 vs -5.2 on a 100-point scale; P = .02) and were less likely to
      consent (odds ratio, 2.27; P = .04). In contrast, subjects evaluating carotid
      endarterectomy and extracranial-to-intracranial bypass were not influenced by
      information order. When subjects were influenced by the order of information,
      they also reported that the treatment's risk had less influence on their decision
      making (P < .01). CONCLUSIONS: When patients evaluate low-risk medical
      interventions, they may form less favorable impressions of the treatment and be
      less likely to consent to the treatment when they learn about the risks after the
      benefits. Order effects were not observed with high-risk treatments regardless of
      potential benefits.

PMID- 12213141
TI  - Geographic variation in health care utilization and outcomes in veterans with
      acute myocardial infarction.
AB  - OBJECTIVES: To examine regional variation in health care utilization and outcomes
      during acute and chronic care of veterans following acute myocardial infarction
      (AMI), identifying potentially modifiable variables and processes of care that
      influence patient outcomes. METHODS: Using national VA databases, we identified
      all veterans hospitalized at any VA Medical Center (VAMC) for AMI between October
      1990 and September 1997. Demographic, inpatient, outpatient, mortality, and
      readmission data were extracted for 4 regions: Northeast, South, Midwest and
      West. Multivariable Cox proportional hazards regression models, controlled for
      comorbidity, were used to assess predictors of time to death and readmission.
      RESULTS: We identified 67,889 patients with AMI. Patient demographic
      characteristics by region were similar. Patients in the Northeast had more
      comorbid conditions and longer lengths of stay during the index AMI
      hospitalization. Region of the country independently predicted time to death,
      with lower risk of death in the Northeast (hazard ratio [HR] = 0.875; 95%
      confidence interval [95% CI], 0.834 to 0.918; P < .0001) and West (HR = 0.856;
      95%CI, 0.818 to 0.895; P = .0001) than in the South. Patients in the Northeast
      and West also had more cardiology or primary care follow-up within 60 days and at
      1 year post-discharge than patients in the South and Midwest. Outpatient follow
      up accounted for a significant portion of the variation in all-cause mortality.
      CONCLUSION: Substantial geographic variation exists in subsequent clinical care
      and outcomes among veterans hospitalized in VAMCs for AMIs. Outpatient follow-up
      was highly variable and associated with decreased mortality. Further studies are
      needed to explore the causes of regional variation in processes of care and to
      determine the most effective strategies for improving outcomes after AMI.

PMID- 12213143
TI  - Advance care planning.
AB  - BACKGROUND: Advance directives (AD) with specific treatment preferences can be
      difficult to apply in actual clinical situations. As an alternative, advance
      directives that outline patient goals and values have been advocated. OBJECTIVE:
      To compare patient reactions to values-based and treatment-based advance
      directive forms. SETTING: Two academic general medicine outpatient clinics in
      Pittsburgh, Pa. METHODS: Outpatients age 55 or older who did not have an AD and
      were not demented were randomly assigned to complete either Emanuel's Medical
      Directive (EMD) or Pearlman's values history (PVH) form. MEASUREMENTS: Length of
      time to complete and number of questions asked about the AD forms; proportions of
      patients discussing the AD with family, designating a surrogate, returning the AD
      by mail, and desiring to have the AD in the medical record; patient ratings of AD
      by telephone interview; physician report of patient-initiated AD discussions.
      RESULTS: Of the 275 patients approached, 143 refused, 69 already had an AD, 63
      patients were enrolled, and 25 in each group completed the telephone interview. A
      majority of individuals in both groups had conversations with others about the AD
      (60% EMD, 56% PVH; P = .77). All PVH forms designated a surrogate, whereas 79% of
      EMD forms did so (P = .02). One patient in each group initiated a conversation
      with his or her physician about AD following study completion. Both forms were
      thought to be a good first step in planning care at the end of life (92% EMD vs
      84% PVH totally or mostly agree; P = .06). Patients completing the EMD thought it
      would give them control over the way their doctor cared for them at the end of
      their lives more than did the PVH group (84% EMD vs 48% PVH totally or mostly
      agree; P = .02). More patients completing the EMD form worried that it would be
      difficult to change answers on the form if they later changed their minds (20%
      EMD vs 4% PVH totally or mostly agree; P = .02). CONCLUSIONS: Both the values
      based and treatment-based AD forms were rated favorably overall. Patients thought
      the treatment-based directive would give them more control over their care.
      Patients completing the values history form were more likely to designate a
      surrogate. Patients are likely to discuss both types of AD with family, but
      neither form alone is likely to lead to AD conversations with physicians.

PMID- 12213145
TI  - Evidence-based medicine knowledge, attitudes, and skills of community faculty.
AB  - CONTEXT: As medical schools turn to community physicians for ambulatory care
      teaching, assessing the preparation of these faculty in principles of evidence
      based medicine (EBM) becomes important. OBJECTIVE: To determine the knowledge and
      attitudes of community faculty concerning EBM and their use of EBM in patient
      care and teaching. DESIGN: Cross-sectional survey conducted from January to March
      of 2000. SETTING: A clinical campus of a state medical school; a midwestern city
      of a half-million people with demographics close to national means. MAIN OUTCOME
      MEASURES: Comparisons of community faculty with full-time faculty in perceived
      importance and understanding of EBM (5-point scale), knowledge of EBM, and use of
      EBM in patient care and teaching. MAIN RESULTS: Responses were obtained from 63%
      (177) of eligible community faculty and 71% (22) of full-time faculty. Community
      faculty considered EBM skills to be less important for daily practice than did
      full-time faculty (3.1 vs 4.0; P < .01). Primary care community faculty were less
      confident of their EBM knowledge than were subspecialty community or full-time
      faculty (2.9 vs 3.3 vs 3.6; P < .01). Objective measures of EBM knowledge showed
      primary care and subspecialty community faculty about equal and significantly
      below full-time faculty (P < .01). Thirty-three percent of community faculty
      versus 5% of full-time faculty do not incorporate EBM principles into their
      teaching (P < .01). CONCLUSIONS: Community faculty are not as equipped or
      motivated to incorporate EBM into their clinical teaching as are full-time
      faculty. Faculty development programs for community faculty should feature how to
      use and teach basic EBM concepts.

PMID- 12213144
TI  - Can a pain management and palliative care curriculum improve the opioid
      prescribing practices of medical residents?
AB  - BACKGROUND: Although opioids are central to acute pain management, numerous
      studies have shown that many physicians prescribe them incorrectly, resulting in
      inadequate pain management and side effects. We assessed whether a case-based
      palliative medicine curriculum could improve medical house staff opioid
      prescribing practices. DESIGN: Prospective chart review of consecutive pharmacy
      and billing records of patients who received an opioid during hospitalization
      before and after the implementation of a curricular intervention, consisting of
      10 one-hour case-based modules, including 2 pain management seminars.
      MEASUREMENTS: Consecutive pharmacy and billing records of patients who were cared
      for by medical residents (n = 733) and a comparison group of neurology and
      rehabilitative medicine patients (n = 273) that received an opioid during
      hospitalization in 8-month periods before (1/1/97 to 4/30/97) and after (1/1/99
      to 4/30/99) the implementation of the curriculum on the medical service were
      reviewed. Three outcomes were measured: 1) percent of opioid orders for
      meperidine; 2) percent of opioid orders with concomminant bowel regimen; and 3)
      percent of opioid orders using adjuvant nonsteroidal anti-inflammatory drugs
      (NSAIDs). MAIN RESULTS: The percentage of patients receiving meperidine decreased
      in the study group, but not in the comparison group. The percentages receiving
      NSAIDs and bowel medications increased in both groups. In multivariate logistic
      models controlling for age and race, the odds of an experimental group patient
      receiving meperidine in the post-period decreased to 0.55 (95% confidence
      interval [95% CI], 0.32 to 0.96), while the odds of receiving a bowel medication
      or NSAID increased to 1.48 (95% CI, 1.07 to 2.03) and 1.53 (95% CI, 1.01 to
      2.32), respectively. In the comparison group models, the odds of receiving a
      NSAID in the post-period increased significantly to 2.27 (95% CI, 1.10 to 4.67),
      but the odds of receiving a bowel medication (0.45; 95% CI, 0.74 to 2.00) or
      meperidine (0.85; 95% CI, 0.51 to 2.30) were not significantly different from
      baseline. CONCLUSIONS: This palliative care curriculum was associated with a
      sustained (>6 months) improvement in medical residents' opioid prescribing
      practices. Further research is needed to understand the changes that occurred and
      how they can be translated into improved patient outcomes.

PMID- 12213146
TI  - Effect of Spanish interpretation method on patient satisfaction in an urban walk
      in clinic.
AB  - OBJECTIVE: To examine the effect of Spanish interpretation method on satisfaction
      with care. DESIGN: Self-administered post-visit questionnaire. SETTING: Urban,
      university-affiliated walk-in clinic. PARTICIPANTS: Adult, English- and Spanish
      speaking patients presenting for acute care of non-emergent medical problems.
      MEASUREMENTS AND MAIN RESULTS: Satisfaction with overall clinic visit and with 7
      provider characteristics was evaluated by multiple logistic regression,
      controlling for age, gender, ethnicity, education, insurance status, having a
      routine source of medical care, and baseline health. "Language-concordant"
      patients, defined as Spanish-speaking patients seen by Spanish-speaking providers
      and English-speaking patients, and patients using AT&T telephone interpreters
      reported identical overall visit satisfaction (77%; P = .57), while those using
      family or ad hoc interpreters were significantly less satisfied (54% and 49%; P <
      .01 and P = .007, respectively). AT&T interpreter use and language concordance
      also yielded similar satisfaction rates for provider characteristics (P > .2 for
      all values). Compared to language-concordant patients, patients who had family
      members interpret were less satisfied with provider listening (62% vs 85%; P =
      .003), discussion of sensitive issues (60% vs 76%; P = .02), and manner (62% vs
      89%; P = .005). Patients who used ad hoc interpreters were less satisfied with
      provider skills (60% vs 83%; P = .02), manner (71% vs 89%; P = .02), listening
      (54% vs 85%; P = .002), explanations (57% vs 84%; P = .02), answers (57% vs 84%;
      P = .05), and support (63% vs 84%; P = .02). CONCLUSIONS: Spanish-speaking
      patients using AT&T telephone interpretation are as satisfied with care as those
      seeing language-concordant providers, while patients using family or ad hoc
      interpreters are less satisfied. Clinics serving a large population of Spanish
      speaking patients can enhance patient satisfaction by avoiding the use of
      untrained interpreters, such as family or ad hoc interpreters.

PMID- 12213147
TI  - Simplifying likelihood ratios.
AB  - Likelihood ratios are one of the best measures of diagnostic accuracy, although
      they are seldom used, because interpreting them requires a calculator to convert
      back and forth between "probability" and "odds" of disease. This article
      describes a simpler method of interpreting likelihood ratios, one that avoids
      calculators, nomograms, and conversions to "odds" of disease. Several examples
      illustrate how the clinician can use this method to refine diagnostic decisions
      at the bedside.

PMID- 12213148
TI  - Paying hypertension research subjects.
AB  - CONTEXT: Cash payments are often used to compensate subjects who participate in
      research. However, ethicists have argued that these payments might constitute an
      undue inducement. OBJECTIVES: To determine whether potential subjects agree with
      theoretical arguments that a payment could be an undue inducement.
      DESIGN/SETTING/PARTICIPANTS: Survey of 350 prospective jurors. MAIN OUTCOME
      MEASURES: Belief that a 500 dollar payment for research participation would
      impair their own, and others' ability to think carefully about the risks and
      benefits of a clinical trial. RESULTS: Two hundred sixty-one jurors (74.6%)
      believed that a 500 dollar payment would impair subjects' ability to think
      carefully about the risks and benefits of research. Ninety-six of 120 (80%)
      expressed this concern about subjects with a low income (<20,000 dollars)
      compared to 92/117 (79%) of those with a middle income (20,000 dollars to 50,000
      dollars), and 73/113 (65%) with a high income (>50,000 dollars). In contrast,
      only 69 (19.7%) of jurors believed that a 500 dollar payment would influence
      them. Jurors who believed that this payment would influence them reported lower
      incomes and less education. CONCLUSION: Members of the general public share
      ethical concerns about the influence of payments for research, although they
      believe that these concerns are more applicable to others than to themselves.

PMID- 12213149
TI  - Hand to hand.
AB  - Examination of the hands has the potential to transform the encounter between
      physician and patient. Taking the hands conveys a sense of warmth and
      connectedness and is a means to communicate the physician's mindfulness. The
      hands can focus the examination on the individual patient as a complete human
      being, and not merely a disease or a collection of symptoms. The hands provide
      readily accessible information that may not be available through other
      evaluations, and they offer clues to a patient's physical and mental health.
      Commonplace observations, such as those revealed in the hands, can unravel
      medical mysteries and provide profound clinical insights.

PMID- 12213150
TI  - Sustained-release preparations and medication errors.

PMID- 12213151
TI  - The care of patients with chronic kidney disease.

PMID- 12213152
TI  - Closing the gaps between urban and rural eye health and eye care services.

PMID- 12213153
TI  - Clinical and Experimental Ophthalmology online.

PMID- 12213154
TI  - Eye health in rural Australia.
AB  - A review of the current literature relating to eye health in rural Australia was
      conducted. Few studies have been undertaken, with most information provided by
      the Australian Institute of Health and Welfare databases, The National Trachoma
      and Eye Health Program of 1980 and the Visual Impairment Project in Victoria in
      the mid 1990s. Key findings were that the rural population has an increased
      prevalence of pterygium, cataract, ocular trauma and glaucoma, but no difference
      in refractive error or diabetic retinopathy (although data are limited). Rural
      residents are more likely to have seen an optometrist but less likely to have
      seen an ophthalmologist. Interventions have been undertaken in ophthalmologist
      training to increase the rural workforce and tele-ophthalmology to provide city
      based metropolitan ophthalmological support for rural practitioners. Further
      epidemiological data and evaluated interventions are urgently required to help
      identify and address the needs of rural Australian communities.

PMID- 12213155
TI  - Orbital and adnexal cysticercosis.
AB  - Orbital and adnexal cysticercosis is emerging as a far commoner disease than
      previously considered, both in endemic and nonendemic areas of cysticercosis. A
      review of the literature on orbital and adnexal cysticercosis found that it has a
      predilection for children and young adults with no definite sex predilection. The
      extraocular muscle form is the commonest type of orbital and adnexal
      cysticercosis. Lodgement of cysts in the subconjunctival space is another common
      site, followed by the eyelid, optic nerve, retro-orbital space and lacrimal
      gland. Association of orbital cysticercosis with systemic cysticercosis is quite
      rare. The clinical manifestations of orbital or adnexal cysticercosis are
      entirely different and depend on the location, size, relation to adjacent
      structures and stage of evolution of the cyst. Diagnosis of cysticercosis is
      based mainly on orbital imaging because of its highly specific appearance. Tissue
      diagnosis is not essential for initiating treatment. Medical therapy is the
      recommended treatment for the extraocular muscle form and retro-orbital cysticer
      cosis. Surgical removal is advocated for subconjunctival and eyelid
      cysticercosis. Because of the limited number of cases of optic nerve and lacrimal
      gland cysticercosis, their treatment is controversial.

PMID- 12213156
TI  - The corneal thickness and intraocular pressure story: where are we now?
AB  - A review of the current literature was conducted regarding the effect of corneal
      thickness on the diagnosis of glaucoma, and the influence of excimer laser
      refractive surgery on intraocular pressure (IOP) measurement with Goldmann
      applanation tonometry. In general, normals and primary open angle glaucoma
      patients have a similar distribution of corneal thickness; however, there is a
      wide variation, ranging from 427 to 716 micro m. Normal tension glaucoma patients
      have a tendency towards thinner corneas than normals; however, there is an
      overlap of thickness measurements of more than two-thirds in 95% of patients.
      There is a trend for ocular hypertensives to have thicker corneas than normals,
      but again there is an overlap of about one-third in 95% of patients. The general
      trend after excimer laser refractive surgery is for a decrease in IOP, with a
      mean fall in IOP measured of 0.63 mmHg per dioptre correction. There is, however,
      a large scatter of values with some patients having the same or lower IOP post
      laser, but with other patients measuring higher pressures. Corneal thickness can
      influence IOP measurement by Goldmann applanation tonometry; however, the
      magnitude of the effect is subject to much individual variation.

PMID- 12213157
TI  - Comparison of clinical optic disc assessment with tests of early visual field
      loss.
AB  - PURPOSE: Clinical optic disc assessment may identify glaucomatous optic
      neuropathy prior to a patient developing visual field abnormalities on achromatic
      automated peri-metry (AAP). Tests targeting axons that are selectively damaged or
      whose redundancy is low, such as short wavelength automated perimetry (SWAP) and
      frequency doubling perimetry (FDP), may detect visual field loss before it is
      seen on AAP. This study investigated whether patients in whom characteristic
      glaucomatous optic disc damage was present without AAP abnormalities had visual
      field abnormalities with SWAP and FDP. METHODS: A sample of patients (n = 50)
      with ocular hypertension (normal AAP) were selected, who had SWAP, FDP and
      stereofundus photography performed. The photographs were then analysed by two
      glaucoma subspecialists who were masked to the assessments of the other and to
      the patients' SWAP and FDP results. A categorization of the optic discs was made
      as either normal or abnormal and this was compared with their SWAP and FDP
      findings. RESULTS: On comparing SWAP and FDP with clinical optic disc assessment
      as the 'gold standard', the sensitivity, specificity, positive predictive value
      (PPV) and negative predictive value (NPV) were 33%, 92%, 57% and 81%,
      respectively, for SWAP and 25%, 89%, 49% and 79%, respectively, for FDP.
      CONCLUSION: In glaucoma suspects, the study suggests that SWAP and FDP identify
      subjects with early glaucomatous optic neuropathy missed by AAP.

PMID- 12213158
TI  - Effect of diode laser contact transscleral pars plana photocoagulation on
      intraocular pressure in glaucoma.
AB  - PURPOSE: To evaluate the efficacy of diode laser contact transscleral pars plana
      photocoagulation (CTPPP) for intraocular pressure (IOP) control in glaucoma and
      its clinical application. METHOD: A prospective, non-randomized hospital-based
      pilot study was conducted. Fourteen patients with poor visual acuity (VA worse
      than 6/60) and medically uncontrolled, refractory glaucoma were recruited, and
      CTPPP was performed after informed consent. RESULTS: Mean preoperative IOP was
      41.0 mmHg (SD 12.6, range 27-70, n = 14). At 1 week postoperatively, IOP was
      reduced in 12 of 14 (86%) patients to a mean of 28.6 mmHg (SD 15.8, range 3-55, n
      = 14). This represented a mean decrease of 12.4 mmHg. Mean IOP was 34.0 mmHg (SD
      17.4, range 5-71, n = 14) and 31.6 mmHg (SD 13.4, range 5-22, n = 12) at 4 and 12
      weeks, respectively. The IOP reduction was significant at 1 week (P = 0.001,
      paired t-test) and at 12 weeks (P = 0.04, paired t-test). The two patients with
      preoperative pain reported abolition of pain after the procedure. Seven of 13
      patients on preoperative antiglaucoma eye drops did not require eye drops
      postoperatively. CONCLUSION: Diode laser CTPPP was found to significantly reduce
      IOP in the majority of patients at 1 week postoperatively, with less but still
      significant effect at 12 weeks. Its potential application as a procedure for
      short-term IOP reduction in medically uncontrolled glaucoma requiring filtering
      surgery needs to be further investigated.

PMID- 12213159
TI  - Role of daunorubicin in inhibiting proliferative vitreoretinopathy after retinal
      detachment surgery.
AB  - PURPOSE: To study the role of daunorubicin in inhibiting proliferative
      vitreoretinopathy after retinal detachment surgery. METHOD: Thirty eyes of 30
      patients with a primary rhegmatogenous retinal detachment and proliferative
      vitreoretinopathy of stage D1 or more advanced were included in the study. The
      eyes were randomly assigned to either the experimental or the control group. The
      eyes in the experimental group received an intravitreal injection of daunorubicin
      (5 microg) before conclusion of the vitrectomy. The main outcome measures
      evaluated were: retinal attachment, vitreous activity and visual acuity at 3
      months after surgery. RESULT: Complete retinal attachment was achieved in 13 eyes
      (86.6%) in the daunorubicin group and 10 eyes (66.6%) in the control group, at 3
      months. Nine patients (60%) in the daunorubicin group and five patients (33.3%)
      in the control group had a best-corrected visual acuity of >or=3/60 at 3 months
      of follow up. There was a statistically significant reduction in vitreous
      reaction at all times during the postoperative period in the daunorubicin group.
      CONCLUSION: Daunorubicin may be a useful drug in inhibiting proliferative
      vitreoretinopathy after surgery for primary rhegmatogenous retinal detachment.

PMID- 12213160
TI  - Late orbital haemorrhage around alloplastic orbital floor implants: a case series
      and review.
AB  - BACKGROUND: Alloplastic implants have been used to repair orbital wall fractures
      and correct anophthalmic enophthalmos (or volume deficiency in an anophthalmic
      socket). Orbital haemorrhage is a rare complication of these implants. METHOD: A
      retrospective review of patient files of two consultant oculoplastic surgeons.
      RESULTS: Four cases of orbital haemorrhage following alloplastic implants were
      identified. The haemorrhages occurred 5-18 years after surgery, and occurred
      within the pseudocapsule of the implant. In one case, recurrent haemorrhages were
      noted. CONCLUSION: Although rare, orbital haemorrhage is a potential complication
      of alloplastic orbital floor implants, which may present many years after
      surgery.

PMID- 12213161
TI  - Respiratory epithelial orbital cysts.
AB  - Congenital or post-traumatic respiratory epithelial lined cysts of the orbit are
      very rare, and such cysts more commonly occur as mucocoeles secondary to chronic
      paranasal sinus disease. Four new cases of such cysts are described herein, three
      presumed choristomas and one occurring after trauma. Two of three presumed
      choristomatous (congenital) cysts occurred in sites that were atypical for the
      commoner dermoid cyst. One occurred in the superior orbit between the superior
      rectus and levator palpebrae superioris muscle and one in the temporal fossa and
      lateral orbit. The third choristomatous lesion occurred in the superotemporal
      orbit with a well-defined bony defect, a typical pattern of the commoner dermoid
      cyst. The fourth case, a presumed traumatic respiratory epithelial cyst, probably
      arose from ethmoidal sinus mucosa. Respiratory epithelial orbital cysts are very
      rare and may occur in sites that are atypical for the commoner orbital dermoid
      cyst.

PMID- 12213162
TI  - Photographic documentation of spontaneous extrusion of a subconjunctival
      cysticercus cyst.
AB  - Spontaneous extrusion of a subconjunctival cysticercus cyst is a rare occurrence.
      The case reported is of a 20-year-old man who presented with a subconjunctival
      cysticercus cyst that was suspected to be undergoing spontaneous extrusion. The
      eye was photographed as the parasite extruded through the conjunctival opening
      with undulating movements over 3-4 min.

PMID- 12213163
TI  - Partial and significant reversal of progressive visual and neurological deficits
      in multiple sclerosis: a possible therapeutic effect.
AB  - A 24-year-old woman developed over 18 months fluctuating and progressively
      increasing visual and cerebellar deficits, due to multiple sclerosis. The minimum
      visual acuities were 3/19 on the right and the perception of finger movement at 1
      m on the left. She became able to walk only with a wide base and with support.
      Her condition deteriorated despite the use of methylprednisolone, prednisone and
      interferon beta-1b, so these were ceased. Azathioprine, 25 mg daily increasing to
      100 mg daily, reducing following abnormal liver function tests to 50 mg daily,
      and glatiramer acetate 20 mg daily were commenced. The visual acuities two months
      later were 3/7.5 on the right and 3/6 on the left and after 4 months 3/4.5 on the
      right and 3/3 on the left. She was able after 2 months to walk unaided on a
      narrow base and after 4 months to jog half a kilometre without difficulty.
      Progressive multiple sclerosis has been held to be irreversible. The response in
      the present case therefore raises the possibility of a drug effect. It indicates
      the need for trials of combined immunomodulatory and immunosuppressive therapies
      in progressive multiple sclerosis.

PMID- 12213164
TI  - Microstructural analysis of Salzmann's nodular degeneration by in vivo confocal
      microscopy.
AB  - A 44-year-old man with symptoms of ocular irritation and corneal changes
      characteristic of Salzmann's nodular degeneration in the left eye was examined
      using in vivo confocal microscopy. In vivo confocal microscopy highlighted an
      irregularly shaped basal epithelium with foci of prominent nuclei, and disrupted
      anterior stromal architecture with increased reflectivity of extracellular matrix
      within the nodules. These observations were consistent with prior
      histopathological descriptions of Salzmann's nodular degeneration. In vivo
      confocal microscopy enhances the clinicopathological assessment of degenerative
      corneal diseases, such as Salzmann's nodular degeneration, without the need for
      biopsy.

PMID- 12213165
TI  - Mycosis fungoides causing severe lower eyelid ulceration.
AB  - Mycosis fungoides is a form of cutaneous malignant T-cell lymphoma initially
      confined to the skin. A range of ophthalmic manifestations has been described;
      these usually appear in advanced disease. Lid involvement is most common and
      ranges from ectropion, usually cicatricial, to diffuse thickening and placoid
      tumours. A case of a 72-year-old man presenting with progressive, full thickness,
      lower eyelid ulceration is presented. The patient had a long history of placoid
      skin lesions, previously diagnosed as discoid lupus. Repeat biopsies of these
      lesions including the eyelid eventually revealed mycosis fungoides. The
      ulceration progressed to destroy most of the lower lid before the correct
      diagnosis was made. This type of eyelid involvement has not previously been
      reported in mycosis fungoides. This case also highlights the diagnostic
      difficulties encountered in the early phases of mycosis fungoides. If suspected,
      multiple biopsies are essential to establish the diagnosis.

PMID- 12213166
TI  - Corticosteroid-induced glaucoma in a child after a scleral reinforcement
      procedure.
AB  - Corticoteroid-induced glaucoma can result from either topical or systemic
      corticosteroid use. Compared with adults, the corticosteroid response in children
      is less well known. The case is reported of a child who developed glaucoma after
      receiving topical corticosteroids following a scleral reinforcement procedure.
      The raised intraocular pressure was controlled after cessation of the
      corticosteroids and with the use of antiglaucoma therapy. As many forms of
      cortico-steroids are widely used, children on corticosteroids should have regular
      intraocular pressure measurements as part of their management.

PMID- 12213167
TI  - Capnocytophaga canimorsus endophthalmitis following cataract surgery.
AB  - An elderly man developed endophthalmitis 1 week after cataract extraction and
      lens implantation. Intraocular samples were collected and the patient received
      intravitreal vanco-mycin and ceftazidime, and topical tobramycin. A Gram stain of
      vitreous humour revealed spindle-shaped Gram-negative bacilli. He was then given
      systemic clindamycin and topical ofloxacin. Capnocytophaga canimorsus, a member
      of the oral flora of dogs and cats, was cultured after 3 days. The infection
      resolved leaving the patient with a visual acuity of 6/60. An attempt was made to
      culture the organism from the mouth of the patient's pet dog. This was
      unsuccessful and the source of the infection remains unknown.

PMID- 12213168
TI  - Orbital dirofilariasis.
AB  - Dirofilariasis is a parasitic disease of domestic and wild animals that
      occasionally may present as zoonotic infection in humans. The microfilariae are
      accidentally transmitted to humans by Culex and Aedes mosquitoes. Ophthalmic
      infections with Dirofilaria are well documented all over the world, including
      America, Europe and Australia. The infection may be periorbital, subconjunctival
      or intraocular. In this report a case is described of orbital dirofilariasis that
      presented as ptosis and lid swelling. Australian ophthalmologists should consider
      dirofilariasis as part of the differential diagnosis of orbital swelling and
      inflammation.

PMID- 12213169
TI  - Branch retinal vein occlusion in Churg-Strauss syndrome.
AB  - The case is reported of a 64-year-old man who was diagnosed as having Churg
      Strauss syndrome associated with branch retinal vein occlusion, without
      accompanying retinal vasculitis. It was assumed that the blood thrombocytosis
      caused a hypercoagulable state and thromboembolism leading to the branch retinal
      vein occlusion.

PMID- 12213170
TI  - Indocyanine green angiographic interpretation of reticular dystrophy of the
      retinal pigment epithelium complicated by choroidal neovascularization.
AB  - A 37-year-old woman presented with flashes in her left eye and bilateral visual
      distortion. Fundal examination revealed a reticular 'fishnet' pattern of retinal
      pigmentation in both eyes consistent with reticular dystrophy of the retinal
      pigment epithelium. In the left eye there was a small haemorrhage and a shallow
      serous macular detachment. Fluorescein angiography demonstrated subfoveal
      choroidal neovascularization. Indocyanine green angiography (ICG) revealed more
      extensive involvement than fluorescein angiography, with small areas of intense
      hyperfluorescence amongst reticular areas of hypofluorescence. These changes, as
      interpreted in light of the known histopathological localization of ICG, are
      consistent with varying stages of dysfunction of the retinal pigment epithelium
      in this disease.

PMID- 12213171
TI  - Trypan blue assisted phacoemulsification by residents in training.

PMID- 12213172
TI  - Abstracts of the 26th SIU, Stockholm, Sweden, 8-12 September 2002.

PMID- 12213183
TI  - Funding source, trial outcome and reporting quality: are they related? Results of
      a pilot study.
AB  - BACKGROUND: There has been increasing concern regarding the potential effects of
      the commercialization of research. METHODS: In order to examine the relationships
      between funding source, trial outcome and reporting quality, recent issues of
      five peer-reviewed, high impact factor, general medical journals were hand
      searched to identify a sample of 100 randomized controlled trials (20
      trials/journal). Relevant data, including funding source (industry/not-for
      profit/mixed/not reported) and statistical significance of primary outcome
      (favouring new treatment/favouring conventional treatment/neutral/unclear), were
      abstracted. Quality scores were assigned using the Jadad scale and the adequacy
      of allocation concealment. RESULTS: Sixty-six percent of trials received some
      industry funding. Trial outcome was not associated with funding source (p=.461).
      There was a preponderance of favourable statistical conclusions among published
      trials with 67% reporting results that favored a new treatment whereas 6%
      favoured the conventional treatment. Quality scores were not associated with
      funding source or trial outcome. CONCLUSIONS: It is not known whether the absence
      of significant associations between funding source, trial outcome and reporting
      quality reflects a true absence of an association or is an artefact of inadequate
      statistical power, reliance on voluntary disclosure of funding information, a
      focus on trials recently published in the top medical journals, or some
      combination thereof. Continued and expanded monitoring of potential conflicts is
      recommended, particularly in light of new guidelines for disclosure that have
      been endorsed by the ICMJE.

PMID- 12213184
TI  - Regular use of aspirin and pancreatic cancer risk.
AB  - BACKGROUND: Regular use of aspirin and other non-steroidal anti-inflammatory
      drugs (NSAIDs) has been consistently associated with reduced risk of colorectal
      cancer and adenoma, and there is some evidence for a protective effect for other
      types of cancer. As experimental studies reveal a possible role for NSAIDs is
      reducing the risk of pancreatic cancer, epidemiological studies examining similar
      associations in human populations become more important. METHODS: In this
      hospital-based case-control study, 194 patients with pancreatic cancer were
      compared to 582 age and sex-matched patients with non-neoplastic conditions to
      examine the association between aspirin use and risk of pancreatic cancer. All
      participants received medical services at the Roswell Park Cancer Institute in
      Buffalo, NY and completed a comprehensive epidemiologic questionnaire that
      included information on demographics, lifestyle factors and medical history as
      well as frequency and duration of aspirin use. Patients using at least one tablet
      per week for at least six months were classified as regular aspirin users.
      Unconditional logistic regression was used to compute crude and adjusted odds
      ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Pancreatic cancer risk
      in aspirin users was not changed relative to non-users (adjusted OR = 1.00; 95%
      CI 0.72-1.39). No significant change in risk was found in relation to greater
      frequency or prolonged duration of use, in the total sample or in either gender.
      CONCLUSIONS: These data suggest that regular aspirin use may not be associated
      with lower risk of pancreatic cancer.

PMID- 12213186
TI  - Growth of Helicobacter pylori in a long spiral form does not alter expression of
      immunodominant proteins.
AB  - BACKGROUND: We have previously reported that altered culture conditions (a broth
      media with shaking) could induce a strain of Helicobacter pylori to assume a long
      spiral morphology resembling that described for Helicobacter heilmannii. The
      present study was initiated to determine if other strains of H. pylori could be
      induced to assume that morphology and if doing so would alter the expression of
      immunodominant proteins. RESULTS: The six strains used in this study were
      American Type Culture Collection 43504, 43579, 49503, 51652, and 51653, and
      Sydney Strain I. Each strain was grown on solid media and in broth culture using
      conditions previously shown to induce the long spiral morphology in strain 43504.
      DNA from each was subjected to urease gene fingerprint analysis. Results of the
      molecular analysis showed identical fingerprint patterns for each strain
      independent of culture source, indicating that only a single strain was present
      in each culture. Expression of immunodominant proteins was assessed by SDS
      polyacrylamide gel electrophoresis and Western blotting with hyperimmune rabbit
      anti H. pylori sera or serum from an H. pylori infected patient. Analysis of
      protein profiles revealed some variation between strains but no significant
      differences associated with morphologic alterations. CONCLUSIONS: These results
      indicate that growth of H. pylori in a long spiral form does not affect
      expression of immunodominant proteins, thus in vivo growth in the long spiral
      form (not documented to date) would not be distinguishable by serology.

PMID- 12213187
TI  - Diagnosis and management of growth hormone deficiency in childhood and
      adolescence--part 2: growth hormone treatment in growth hormone deficient
      children.

PMID- 12213188
TI  - Pharmacokinetics and acute lipolytic actions of growth hormone. Impact of age,
      body composition, binding proteins, and other hormones.
AB  - The biologic actions of endogeneous growth hormone (GH) depend on its secretion
      and clearance rates as well as sensitivity at the receptor level. Aberrations in
      GH pharmacokinetics and pharmacodynamics may occur with increasing age, and have
      been implicated in diseases such as obesity, diabetes mellitus, and critical
      illness. In this review, recent insights into the association between GH
      metabolism and age, body composition, binding proteins and other hormones are
      discussed.

PMID- 12213189
TI  - Differential regulation of pregnancy associated plasma protein (PAPP)-A during
      pregnancy in human and mouse.
AB  - Serum IGFBP-4 proteolytic activity increases dramatically during human pregnancy
      and is mainly attributed to the pregnancy-associated plasma protein-A (PAPP-A).
      To understand the regulation and actions of PAPP-A in vivo, we evaluated the
      utility of a mouse model system. Serum from day-9 and day-17 pregnant mice and
      age-matched controls was tested for IGFBP-4 proteolytic activity using
      recombinant mouse IGFBP-4 as the substrate. Surprisingly, IGFBP-4 proteolytic
      activity in mouse pregnancy serum (mPS) was not significantly different from that
      of non-pregnancy serum (mNPS). Addition of IGF-II to mPS or mNPS at a dose
      sufficient to increase IGFBP-4 proteolysis by human PS failed to enhance IGFBP-4
      proteolysis. PAPP-A neutralization antibody did not inhibit IGFBP-4 proteolysis
      by mPS or mNPS, but completely blocked IGFBP-4 proteolytic activity in human PS
      (hPS, mouse osteoblast conditioned medium, and mouse amniotic fluid). To
      determine whether the lack of PAPP-A activity in mPS was due to low expression of
      PAPP-A in the placenta, we cloned a mouse genomic DNA, which contained 1 kb of
      the entire exon 2 coding sequence and 2.5 kb of the flanking intron sequences.
      The exon 2-coded mouse and human PAPP-A shared 86% amino acid sequence identity.
      RT-PCR analysis revealed that the PAPP-A mRNA level in mouse placenta was lower
      compared to that in human placenta by at least two orders of magnitude. PAPP-A
      expression was also lower in mouse placenta compared to those in mouse kidney,
      osteoblasts, and bone marrow stromal cells. CONCLUSIONS: (1) Serum IGFBP-4
      proteolytic activity is differentially regulated by pregnancy in human and mouse.
      (2) The lack of an increase in serum IGFBP-4 proteolytic activity during mouse
      pregnancy is due to the low level of PAPP-A expression in the placenta.

PMID- 12213190
TI  - Growth and maturational changes in dense fibrous connective tissue following 14
      days of rhGH supplementation in the dwarf rat.
AB  - The purpose of this study was to investigate the impact of recombinant human
      growth hormone (rhGH) on patella tendon (PT), medial collateral ligament (MCL),
      and lateral collateral ligament (LCL) on collagen growth and maturational changes
      in dwarf GH-deficient rats. Twenty male Lewis mutant dwarf rats, 37 days of age,
      were randomly assigned to Dwarf + rhGH (n = 10) and Dwarf + vehicle (n = 10)
      groups. The GH group received 1.25 mg rhGH/kg body wt twice daily for 14 days.
      rhGH administration stimulated dense fibrous connective tissue growth, as
      demonstrated by significant increases in hydroxyproline specific activity and
      significant decreases in the non-reducible hydroxylysylpyridinoline (HP) collagen
      cross-link contents. The increase in the accumulation of newly accreted collagen
      was 114, 67, and 117% for PT, MCL, and LCL, respectively, in 72 h. These findings
      suggest that a short course rhGH treatment can affect the rate of new collagen
      production. However, the maturation of the tendon and ligament tissues decreased
      18-25% during the rapid accumulation of de novo collagen. We conclude that acute
      rhGH administration in a dwarf rat can up-regulate new collagen accretion in
      dense fibrous connective tissues, while causing a reduction in collagen
      maturation.

PMID- 12213191
TI  - Intracellular signaling by growth hormone variant (GH-V).
AB  - Placental growth hormone, or growth hormone variant (GH-V), is a member of the
      growth hormone gene family. Its physiologic role during pregnancy remains
      undefined. Although extensive work has been done characterizing the signaling
      pathways activated by hGH, the signaling pathways which are activated by GH-V
      have not been characterized. We investigated cellular signaling by GH-V in model
      systems in which signaling by hGH has been well characterized. GH-V activates the
      STAT5b transcription factor in the IM-9 human lymphocyte and 3T3-F442A
      preadipocyte cell lines, and in primary porcine smooth muscle cells, which all
      homologously express GH receptors. In contrast, hCS does not activate signaling
      in these GH receptor-expressing cells. Like hGH, signaling by GH-V is inhibited
      by the GH antagonist (G120K). These results provide preliminary evidence that GH
      V plays a major role in affecting target cells expressing the GH receptor, thus
      potentially exerting significant GH-like effects on maternal physiology during
      pregnancy.

PMID- 12213193
TI  - Multiplexing of canine microsatellite markers for whole-genome screens.
AB  - A set of 172 canine microsatellite markers, termed minimal screening set 1
      (MSS1), was recently characterized for use in whole-genome screens. We report
      here the multiplexing of 155 MSS1 markers into 48 multiplex sets. Amplification
      of the multiplex sets is achieved using a single thermal cycling program. The
      markers are labeled with fluorescent dyes and optimized for resolution on an ABI
      310 Genetic Analyzer or ABI 377 Sequencer. The multiplexing strategy involves
      amplifying combinations of markers so that no two markers with the same dye and
      product size overlap. Multiplexing the MSS1 provides an efficient tool for the
      collection of genotypes and streamlines whole-genome screens. Screening the
      canine genome for linkage of markers with various hereditary diseases facilitates
      identification of affected and carrier individuals, thereby providing researchers
      and clinicians with an additional diagnostic tool.

PMID- 12213192
TI  - Alternative splicing of brain-specific PTB defines a tissue-specific isoform
      pattern that predicts distinct functional roles.
AB  - Splicing of neural-specific exons is differentially regulated in neuronal and non
      neuronal cells. The polypyrimidine tract binding protein (PTB) has been
      implicated as a negative regulator for exon splicing, whereas the brain-specific
      homolog of PTB, termed nPTB, promotes exon splicing exclusively in neurons. We
      have now isolated a novel mRNA splice variant of nPTB from non-neuronal cells. In
      contrast to the neural nPTB transcript, the expression of this novel isoform was
      absent from brain tissue and was generated in non-neuronal cells by alternative
      splicing to include five additional amino acid residues encoded by exon 9. In
      addition, we identified a brain-specific transcript containing a novel,
      alternatively spliced, internal exon 10. The exclusion of this 34-nucleotide exon
      10 in non-neuronal tissues generates a premature termination codon and results in
      the truncation of the open reading frame. Our findings suggest that alternative
      splicing of nPTB has an important role in regulation of tissue-specific gene
      expression and thus in the functional activity of nPTB in neuronal and non
      neuronal cells.

PMID- 12213194
TI  - A single-nucleotide polymorphism of SMARCB1 in human breast cancers.
AB  - The gene SMARCB1 has been considered a candidate for a tumor-suppressor gene.
      Nucleotide alterations in SMARCB1 have been reported, primarily in association
      with malignant rhabdoid tumor cases. We carried out a search for mutations in
      SMARCB1 in 60 human gastro-intestinal tract carcinoma cases, 122 breast cancer
      cases, and 36 human cancer cell lines. A single-nucleotide polymorphism (SNP) at
      codon 152 with an amino acid change (Asn to Asp) was found in 2 of 122 (1.6%)
      breast cancer cases, and another SNP at codon 299 without an amino acid change
      was found in tumor and normal tissues from 7 (5.7%) cases. Codons 152 and 299 of
      SMARCB1 are localized near or within the binding site for the cMYC protein. The
      amount of immunoprecipitated cMYC protein was reduced in two different cell lines
      expressing the codon 152 polymorphic SMARCB1 clone compared with those expressing
      wild-type SMARCB1, regardless of the identical expression of SMARCB1 protein in
      both cell lines. Therefore, the SNP at codon 152 is considered to be one of the
      coding SNPs that alters the SMARCB1-cMYC complex, which regulates various tumor
      suppressor related genes against cancer. In addition, we identified three types
      of splicing isoforms, a 27-bp deleted gene, a 51-bp inserted gene, and a
      consensus gene, in both carcinoma tissues and in normal tissues; however, no
      clinical significance was observed for those isoforms. We found a nucleotide
      change at codon 152 of SMARCB1 that may alter the amount of immunoprecipitated
      cMYC protein, but we finally determined that SMARCB1 is highly conserved in human
      solid carcinomas.

PMID- 12213195
TI  - A new gene family (FAM9) of low-copy repeats in Xp22.3 expressed exclusively in
      testis: implications for recombinations in this region.
AB  - Illegitimate recombinations between low-copy repetitive elements (LCR) have been
      implicated in the pathogenesis of various chromosomal rearrangements. Two such
      duplicons have been reported previously on Xp22.3, the CRI-S232 elements,
      involved in the generation of deletions in the steroidsulfatase gene and five
      members of the G1.3 (DXF22S) repetitive sequence family. By molecular
      characterization of an Xp22/10q24 translocation, we identified one duplicon of
      the G1.3 family in the breakpoint region in Xp22.3. We show that G1.3 elements
      harbor at least three expressed genes, FAM9A, FAM9B, and FAM9C, and three
      putative pseudogenes, all mapped to Xp22.33-p22.31. The deduced amino acid
      sequence of the three novel proteins shows homology to SYCP3, a component of the
      synaptonemal complex located along the paired chromosomes during meiosis. FAM9A,
      FAM9B, and FAM9C are expressed exclusively in testis; their proteins are located
      in the nucleus, and FAM9A localizes to the nucleolus. The presence of genes
      within duplicons may represent putative recombination-promoting factors for
      actively transcribed genes in meiotic cells, with the resulting open chromatin
      structure facilitating unequal crossing-over events and chromosomal
      rearrangements.

PMID- 12213196
TI  - Lipase H, a new member of the triglyceride lipase family synthesized by the
      intestine.
AB  - We report here the molecular cloning of a novel member of the triglyceride lipase
      family, a 2.4-kb cDNA encoding human lipase H (LIPH) and the mouse ortholog
      (Liph). The human LIPH cDNA encodes a 451-amino-acid protein with a lipase
      domain. Mouse Liph shows 85% amino acid identity and 75% nucleotide identity to
      human LIPH. Human LIPH exhibits 47% identity with phosphatidylserine-specific
      phospholipase A1 (PS-PLA1) and 46% identity with endothelial lipase (LIPG) and
      lipoprotein lipase (LPL). LIPH is localized on human chromosome 3q27-q28.
      Northern blot analysis revealed specific expression of LIPH mRNA in intestine,
      lung, and pancreas. Lipase H protein was also detected in human intestine. Lipase
      H is a secreted protein with an apparent molecular weight of 63 kDa. Although
      several lipid substrates were tested, the lipid substrate of LIPG was not
      identified. Like the other members of this gene family, LIPH may be involved in
      lipid and energy metabolism.

PMID- 12213197
TI  - Genetics of colitis susceptibility in IL-10-deficient mice: backcross versus F2
      results contrasted by principal component analysis.
AB  - Interleukin-10-deficient (Il10(-/-)) mice on a C3H/HeJBir genetic background
      develop more severe colitis than those on a C57BL/6J background. We performed
      genome screens for quantitative trait loci (QTLs) regulating colitis
      susceptibility in this model system using two first backcross populations derived
      from these two strains. To reduce the complexity of this analysis, the
      information from numerous histologic phenotypes was summarized by principal
      component analysis. A similar approach was applied to previously published data
      from an F2 intercross (involving the same progenitor strains), which allowed us
      to ascertain all six previously reported cytokine-deficiency-induced colitis
      susceptibility loci (Cdcs1-6) with main and/or interacting effects on chromosomes
      3, 1, 2, 8, 17, and 18. The colitogenic effect of Cdcs1 was confirmed in the
      backcross to C3H/HeJBir-Il10(-/-). Its effect was epistatically modified by
      another locus on chromosome 12. In addition, three main effect QTLs on
      chromosomes 4, 5, and 12 were identified in the backcross to C57BL/6J-Il10(-/-).
      Analyses of the modes of inheritance in these crosses revealed colitogenic
      contributions by both parental genomes. These findings show the complexity of
      inheritance underlying susceptibility to colitis and illustrate why detection of
      human inflammatory bowel disease loci has proven to be so difficult.

PMID- 12213198
TI  - The RAY1/ST7 tumor-suppressor locus on chromosome 7q31 represents a complex multi
      transcript system.
AB  - We recently identified a novel gene, RAY1 (FAM4A1), which spans a translocation
      breakpoint at 7q31 in a patient with autism. This gene has more recently been
      reported to be a suppressor of tumorigenicity, ST7, although controversy
      surrounds this observation because subsequent reports have failed to corroborate
      these findings. Our further analysis of this locus reveals that it is composed of
      a multigene system that includes two noncoding sense strand genes (ST7OT3 and
      ST7OT4) that overlap with many alternative forms of the coding RAY1/ST7
      transcript, and two noncoding genes on the antisense strand (ST7OT1 and ST7OT2).
      RAY1/ST7 was determined to have at least three different 5' exons with
      alternative start codons, one of which seems to be used almost exclusively in the
      brain. We have also identified a third alternative 3' end of RAY1/ST7 that uses
      exons from ST7OT3. ST7OT3 spans from intron 10 to exon 14 of RAY1/ST7 and
      includes several exons. ST7OT4 has at least seven exons and is transcribed on the
      sense strand between RAY1/ST7 exon 1 and a tropomyosin-like sequence, TPM3L2.
      ST7OT1 overlaps with the RAY1/ST7 exon 1 and promoter. ST7OT2 spans from RAY1/ST7
      intron 9 to intron 1, and has multiple isoforms. We screened the exons of
      RAY1/ST7 and ST7OT1-3 for sequence variants in 90 unrelated autism probands and
      identified several rare variants, including a Ile361Val substitution. Although
      these variants were not observed in a control population, it is unclear whether
      they contribute to the autistic phenotype. We postulate that the apparent
      noncoding genes at the RAY1/ST7 locus may be regulatory RNAs. The RAY1/ST7 may
      generate at least 18 possible isoforms, with many more arising if other sense
      strand exons from ST7OT3 and ST7 OT4 are used in a selective and possibly tissue
      specific manner.

PMID- 12213199
TI  - DEFOG: a practical scheme for deciphering families of genes.
AB  - We developed a novel efficient scheme, DEFOG (for "deciphering families of
      genes"), for determining sequences of numerous genes from a family of interest.
      The scheme provides a powerful means to obtain a gene family composition in
      species for which high-throughput genomic sequencing data are not available.
      DEFOG uses two key procedures. The first is a novel algorithm for designing
      highly degenerate primers based on a set of known genes from the family of
      interest. These primers are used in PCR reactions to amplify the members of the
      gene family. The second combines oligofingerprinting of the cloned PCR products
      with clustering of the clones based on their fingerprints. By selecting members
      from each cluster, a low-redundancy clone subset is chosen for sequencing. We
      applied the scheme to the human olfactory receptor (OR) genes. OR genes
      constitute the largest gene superfamily in the human genome, as well as in the
      genomes of other vertebrate species. DEFOG almost tripled the size of the initial
      repertoire of human ORs in a single experiment, and only 7% of the PCR clones had
      to be sequenced. Extremely high degeneracies, reaching over a billion
      combinations of distinct PCR primer pairs, proved to be very effective and
      yielded only 0.4% nonspecific products.

PMID- 12213200
TI  - Sequencing, transcript identification, and quantitative gene expression profiling
      in the breast cancer loss of heterozygosity region 16q24.3 reveal three potential
      tumor-suppressor genes.
AB  - Loss of heterozygosity (LOH) of chromosome 16q24.3 is a common genetic alteration
      observed in invasive ductal and lobular breast carcinomas. We constructed a
      physical map and generated genomic DNA sequence data spanning 2.4 Mb in this
      region. Detailed in silico and in vitro analyses of the genomic sequence data
      enabled the identification of 104 genes. It was hypothesized that tumor
      suppressor genes would exhibit marked mRNA expression variability in a panel of
      breast cancer cell lines as a result of downregulation due to mutation or
      hypermethylation. We examined the mRNA expression profiles of the genes
      identified at 16q24.3 in normal breast, a normal breast epithelial cell line, and
      several breast cancer cell lines exhibiting 16q24.3 LOH. Three of the genes,
      CYBA, Hs.7970, and CBFA2T3, exhibited variability ten times higher than the
      baseline. The possible role of these genes as tumor suppressors is discussed.

PMID- 12213201
TI  - Functional and structural characterization of the human gene BHLHB5, encoding a
      basic helix-loop-helix transcription factor.
AB  - The genes encoding basic helix-loop-helix (bHLH) transcription factors have been
      implicated in many aspects of neural development, including cell growth,
      differentiation, and cell migration. Using both genomic and cDNA mouse and human
      clones encoding a neural-specific bHLH protein, human BHLHB5 was cloned and
      mapped to a region on chromosome 8q13 that segregates with Duane syndrome.
      Genomic sequence analysis of human BHLHB5 and mouse Bhlhb5 revealed that they
      contain a single exon encoding 381- and 355-amino-acid bHLH proteins,
      respectively. Multiple amino acid sequence alignments of the Bhlhb5 family
      members revealed several conserved motifs and an identical 147-amino-acid carboxy
      terminal region that contains a 60-amino-acid bHLH domain. A 27-bp trinucleotide
      repeat (CAG)(9) encoding polyserine was found in human BHLHB5, but only one CAG
      was found at the corresponding position in the mouse Bhlhb5 and hamster BETA3
      genes. Northern blot analysis of human BHLHB5 revealed brain-specific expression
      with the highest abundance in the cerebellum. Mouse Bhlhb5 can strongly repress a
      human PAX6 promoter.

PMID- 12213202
TI  - Ovol2, a mammalian homolog of Drosophila ovo: gene structure, chromosomal
      mapping, and aberrant expression in blind-sterile mice.
AB  - The ovo gene family consists of evolutionarily conserved genes including those
      cloned from Caenorhabditis elegans, Drosophila melanogaster, mouse, and human.
      Here we report the isolation and characterization of mouse Ovol2 (also known as
      movol2 or movo2) and provide evidence supporting the existence of multiple Ovol2
      transcripts. These transcripts are produced by alternative promoter usage and
      alternative splicing and encode long and short OVOL2 protein isoforms, whose
      sequences differ from those previously reported. Mouse and human OVOL2 genes are
      expressed in overlapping tissues including testis, where Ovol2 expression is
      developmentally regulated and correlates with the meiotic/postmeiotic stages of
      spermatogenesis. Mouse Ovol2 maps to chromosome 2 in a region containing blind
      sterile (bs), a spontaneous mutation that causes spermatogenic defects and germ
      cell loss. No mutation has been detected in the coding region of Ovol2 from bs
      mice, but Ovol2 transcription was dramatically reduced in testes from these mice,
      suggesting that Ovol2 is expressed in male germ cells.

PMID- 12213203
TI  - Computational analysis of alternative splicing using EST tissue information.
AB  - Expressed sequence tags (ESTs) from normal and tumor tissues have been deposited
      in public databases. These ESTs and all mRNA sequences were aligned with the
      human genome sequence using LEADS, Compugen's alternative splicing modeling
      platform. We developed a novel computational approach to analyze tissue
      information of aligned ESTs in order to identify cancer-specific alternative
      splicing and gene segments highly expressed in particular cancers. Several genes,
      including one encoding a possible pre-mRNA splicing factor, displayed cancer
      specific alternative splicing. In addition, multiple candidate gene segments
      highly expressed in colon cancers were identified.

PMID- 12213204
TI  - The human endogenous retrovirus family HERV-K(HML-3).
AB  - A substantial amount of the human genome is composed of human endogenous
      retroviruses (HERVs). Manifold HERV families have been identified, among them
      several so-called HERV-K(HML) families. Although the HERV-K(HML-2) family has
      been studied in detail, other HERV-K families are not as well characterized. We
      describe here the HERV-K HML-3 family in more detail. We estimate that there are
      about 140 proviral loci or remains of such per haploid genome. Most loci are
      severely mutated. Proviruses displaying larger deletions in gag and pol are
      common. A multiple alignment of 73 HERV-K(HML-3) sequences displays several
      potentially important differences compared with the HERVK9I sequence in Repbase.
      A consensus sequence with open reading frames for all retroviral genes was
      generated, for which intact dUTPase motifs and env gene variants with different
      coding capacities are observed. Phylogenetic analysis shows near-monophyly with
      distinction of two closely related subgroups. Proviruses formed about 36 million
      years ago. However, no continuous activity through primate evolution is
      indicated.

PMID- 12213205
TI  - Mouse Atf5: molecular cloning of two novel mRNAs, genomic organization, and
      odorant sensory neuron localization.
AB  - The activating transcription factor (ATF) family comprises a group of basic
      region-leucine zipper (bZIP) proteins, which have roles in the development of
      species as diverse as insects and mammals. Here we describe two novel mRNAs
      encoding a single, 30-kDa mouse polypeptide, designated mouse ATF5, which is 58%
      identical to mouse ATF4 in the carboxy-terminal bZIP region. Both transcripts
      harbor highly complex 5' untranslated regions that impede translation of the ATF5
      open reading frame. The mouse and human ATF5 loci consist of at least four exons
      contained within 5 kb of genomic sequence. During mouse embryonic development,
      expression of Atf5 is pronounced at the late gestational period and appears to be
      confined to cells of the neuronal layers of the olfactory epithelium and
      vomeronasal organ. This suggests a role for ATF5 in odorant sensory neuron
      differentiation.

PMID- 12213206
TI  - Assessing DNA sequence variations in human ESTs in a phylogenetic context using
      high-density oligonucleotide arrays.
AB  - We have analyzed human genomic diversity in 32 individuals representing four
      continental populations of Homo sapiens in the context of four ape species. We
      used DNA resequencing chips covering 898 expressed sequence tags (ESTs),
      corresponding to 109 kb of sequence. Based on the intra-species data, the neutral
      hypothesis could not be rejected. However, the mutation rate was two times lower
      than typically observed in functionally unconstrained genomic segments,
      suggesting a certain level of selection. The worldwide diversity (297 segregating
      sites and nucleotide diversity of 0.054%) was partitioned among continents, with
      the greatest amount of variation observed in the African sample. The long-term
      effective population size of the human population was estimated at 13,000; a
      similar figure was obtained for the African sample and a 20% lower estimate was
      obtained for the other continents. Africans also differed in having a higher
      number of continental-specific polymorphisms contributing to the higher average
      nucleotide diversity. These results are consistent with the existence of two
      distinct lineages of modern humans: amalgamation of these lineages in Africa led
      to the higher present-day diversity on that continent, whereas colonization of
      other continents by one of them gave the effect of a population bottleneck.

PMID- 12213207
TI  - Transcriptome analysis of monocytic leukemia cell differentiation.
AB  - The human leukemia cell line U937 is a well-established model for studying
      monocytic cell differentiation. We used a modified protocol (SADE) of serial
      analysis of gene expression (SAGE) and developed a SADE linker-anchored PCR assay
      to investigate the pattern of expression of known genes and to identify new
      transcripts in proliferating cells and during cell growth arrest and
      differentiation. We implemented new informatic tools to compare expression
      profiles before and after exposure of cells to differentiation inducers. From the
      analysis of 47,388 tags, we identified 13,806 distinct transcripts, 265 of which
      showed significant variations (P<0.01). Among 1219 well-identified genes, major
      changes concerned transcription and translation components, cytoskeleton, and
      macrophage-specific genes. Nearly half of the tags, some of them expressed at
      high levels, matched partially characterized genes or ESTs, or revealed yet
      unknown transcripts, providing a wealth of new candidate genes that may reveal
      novel aspects of terminal monocytic differentiation.

PMID- 12213208
TI  - Four distinct chondrocyte populations in the fetal bovine growth plate: highest
      expression levels of PTH/PTHrP receptor, Indian hedgehog, and MMP-13 in
      hypertrophic chondrocytes and their suppression by PTH (1-34) and PTHrP (1-40).
AB  - Differentiation and growth of chondrocytes in fetal growth plates of vertebrate
      long bones and ribs appear to occur in a gradual, continuous manner between the
      resting zone through the proliferation zone, maturation zone, and upper and lower
      hypertrophic zones, with a continuous increase in cell size up to 10-fold of the
      volume of a resting chondrocyte. Here we provide evidence, however, that after
      centrifugation through a continuous Percoll gradient growth plate chondrocytes
      separate into four distinct cell populations (B1 to B4) which differ markedly in
      density, size, and gene expression. These populations collect in the absence of
      any phase borders in the gradient which might serve as concentration barriers.
      Fractions B1 and B2 contained the largest cells with the lowest buoyant density
      and showed the highest expression levels for type X collagen (Col X), but only
      the B1 population expressed high levels of matrix metalloproteinase-13
      (collagenase 3). Cells in fraction B3 were significantly smaller and expressed
      little Col X, while cells in fraction B4 were of similar size to cells in the
      resting zone without significant Col X expression. The highest levels of
      parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor (PTHR-1), and
      Indian hedgehog (Ihh) expression were also found in the hypertrophic fractions B1
      and B2 and not in the prehypertrophic fraction B3, as expected from in situ
      hybridization data on PTHR-1 expression in fetal rodent or chicken growth plates.
      Incubation of fractions B1 to B3 with the amino-terminal fragments PTH (1-34) or
      PTHrP (1-40) suppressed the expression of Col X and PTHR-1 by more than 50% and
      the expression of Ihh nearly completely. In contrast, the mid-regional PTH
      fragment PTH (28-48) and PTH (52-84) consistently stimulated the expression of
      PTHR-1 by 10-20% in fractions B1 to B3. These findings confirm the existence of
      distinct differentiation stages within chondrocytes of the growth plate and
      support the hypothesis proposed by Vortkamp et al. (Science 273(1996)613) of a
      regulatory feedback loop of Ihh and PTH/PTHrP fragments controlling the
      differentiation of proliferating to prehypertrophic chondrocytes, but extend the
      ability to respond to PTH/PTHrP hypertrophic chondrocytes.

PMID- 12213209
TI  - Furrow-specific endocytosis during cytokinesis of zebrafish blastomeres.
AB  - Mutations affecting endocytosis, such as those in clathrin and dynamin,
      unexpectedly cause defects in cytokinesis in a number of organisms. To explore
      the relationship between endocytosis and cytokinesis, we used the relatively
      large cells of the transparent zebrafish embryo. Using fluorescent markers for
      fluid-phase as well as plasma membrane uptake, we demonstrate that cytokinesis
      involves furrow-specific endocytosis. Clathrin-coated pits are visible near the
      furrow in ultrathin sections, while immunolabeling demonstrates that clathrin and
      caveolin are localized to the cleavage furrow. Hence, it is likely that both
      clathrin- and caveolae-mediated endocytosis occurs at the furrow during
      cytokinesis. Dynamin II is also localized to the furrow and may mediate furrow
      specific endocytosis. Treatment of embryos with chlorpromazine or with methyl
      beta-cyclodextrin, both of which inhibit endocytosis, prevents the normal
      completion of cytokinesis. These data suggest that furrow-specific endocytosis is
      an integral part of cytokinesis.

PMID- 12213210
TI  - The WASP-binding protein WIRE has a role in the regulation of the actin filament
      system downstream of the platelet-derived growth factor receptor.
AB  - Activation of growth factor receptors, such as platelet-derived growth factor
      (PDGF) receptors, has a major impact on the motile behavior of vertebrate cells.
      The WASP family of proteins has been recognized as important regulators of actin
      polymerization via the activation of the Arp2/3 complex. The activity of the WASP
      proteins has, in turn, been shown to be governed by a number of associated
      proteins, including the WASP interacting protein (WIP). This report presents a
      novel WIP-like protein, WIRE (for WIP-related). WIRE was shown to bind to the WH1
      domain of WASP and N-WASP. WIRE was localized to actin filaments in transiently
      transfected PAE/PDGFRbeta cells, and in cells simultaneously expressing WIRE and
      WASP, WIRE relocalized WASP to actin filaments, a relocalization that required
      direct interaction between the two proteins. In addition, WIRE was able to bind
      the PDGF receptor substrate Nckbeta. PDGF treatment of cells ectopically
      expressing WIRE resulted in formation of peripheral protrusions composed of
      filopodia and lamellipodia-like structures. In cells expressing both WIRE and
      WASP, PDGF treatment induced a translocation of WASP to the cell margin, an
      effect that required the presence of WIRE. Taken together, the data presented
      indicate that WIRE has a role in the WASP-mediated organization of the actin
      cytoskeleton and that WIRE is a potential link between the activated PDGF
      receptor and the actin polymerization machinery.

PMID- 12213211
TI  - Gene delivery to adult neural stem cells.
AB  - Neural stem cells may present an ideal route for gene therapy as well as offer
      new possibilities for the replacement of neurons lost to injury or disease.
      However, it has proved difficult to express ectopic genes in stem cells. We
      report methods to introduce genes into adult neural stem cells using viral and
      nonviral vectors in vitro and in vivo. Adenoviral and VSV-G-pseudotyped
      retroviral vectors are more efficient than plasmid transfection or VSV-G
      lentiviral transduction in vitro. We further show that adult neural stem cells
      can be directed to a neuronal fate by ectopic expression of neurogenin 2 in
      vitro. Plasmids can be delivered in vivo when complexed with linear
      polyethyleneimine, and gene expression can be targeted specifically to neural
      stem or progenitor cells by the use of specific promoters. These techniques may
      be utilized both to study the function of various genes in the differentiation of
      neural stem cells to specific cell fates and, ultimately, for gene therapy or to
      generate specific differentiated progeny for cell transplantation.

PMID- 12213212
TI  - Suppression of the transformed phenotype of breast cancer by tropomyosin-1.
AB  - Changes in the expression of microfilament-associated proteins, such as
      tropomyosins (TMs), are commonly found in malignantly transformed cells. Previous
      work from this laboratory has shown that tropomyosin-1 (TM1) expression is
      consistently abolished in human breast carcinoma cell lines, suggesting that the
      loss of TM1 could be a common biochemical event in the transformation of mammary
      epithelium. To investigate whether changes in TM1 expression are causally linked
      to mammary carcinogenesis, we have tested the hypothesis that TM1 is a tumor
      suppressor of breast cancer. MCF-7 cells, which lack TM1, were utilized as a
      model of human breast cancer and transduced to reexpress TM1 protein. Restoration
      of TM1 expression in MCF-7 cells (MCF-7/T cells) resulted in a slower growth
      rate, but cells remained sensitive to growth control by estrogen. TM1 expression
      in MCF-7 cells resulted in the emergence of TM-containing microfilaments. More
      significantly, MCF-7/T cells failed to grow under anchorage-independent
      conditions. TM1 reexpression alters the interaction of the E-cadherin-catenin
      complex with the cytoskeleton, indicating that TM1-induced cytoskeleton could
      play a significant role in suppression of the malignant phenotype. Taken together
      with our previous work on transformed murine fibroblasts, the results presented
      in this communication indicate that in nonmuscle cells TM1 functions as a
      suppressor of transformation.

PMID- 12213213
TI  - Semaphorin 3E/collapsin-5 inhibits growing retinal axons.
AB  - During development, the formation of neural networks is reflected by the oriented
      extension of neurites. Using retinal ganglion cells (RGCs) as a model, we
      identified the yet uncharacterized chick semaphorin Sema3E/collapsin-5 as a
      repulsive cue for outgrowing axons. Sema3E/collapsin-5 was highly regulated
      during retinal histogenesis, with peak expression during the period of
      intraretinal axon growth. Polymerase chain reaction analysis demonstrated
      Sema3E/collapsin-5 mRNA in retina layers, from which RGC axons are excluded.
      Neither isolated RGCs nor purified retinal Muller glia cells synthesized
      Sema3E/collapsin-5. Sema3E/collapsin-5 receptor sites were visualized by alkaline
      phosphatase fusion proteins in the axon-rich optic fiber layer. Time-lapse video
      recording of chick in vitro cultures revealed a growth cone collapsing activity
      of recombinant Sema3E/collapsin-5. This effect was specific for RGCs, since
      dorsal root ganglia (DRG) neurons of the peripheral nervous system were not
      affected. Comparison with Sema3A/collapsin-1 displayed a reciprocal specificity,
      because Sema3A/collapsin-1 hampered exclusively DRG but not RGC growth cones. The
      collapsing effect was mediated by low cGMP levels, but not cAMP, as revealed by a
      set of agonists. In summary, the data suggest a possible role of chick
      Sema3E/collapsin-5 in restricting growth of retinal ganglion cell axons to the
      optic fiber layer.

PMID- 12213214
TI  - Study of gene expression in thyrotropin-stimulated thyroid cells by cDNA
      expression array: ID3 transcription modulating factor as an early response
      protein and tumor marker in thyroid carcinomas.
AB  - Induction of cell proliferation by mitogen or growth factor stimulation leads to
      the specific induction or repression of a large number of genes. To identify
      genes differentially regulated by the cAMP-dependent transduction pathway, which
      is poorly characterized so far, we used the cDNA expression array technology.
      Hybridizations of Atlas human cDNA expression arrays with (32)P-labeled cDNA
      probes derived from control or thyrotropin (TSH)-stimulated dog thyrocytes in
      primary culture generated expression profiles of hundreds of genes
      simultaneously. Among the genes that displayed modified expression, we selected
      the transcription factor ID3, whose expression was increased by a cAMP-dependent
      stimulus. ID3 overexpression after TSH stimulation was first verified by Northern
      blotting analysis, and its mRNA regulation was then investigated in response to a
      variety of agents acting on thyrocyte proliferation and/or differentiation. We
      show that: (1) ID3 mRNA induction was stronger after stimulation of the cAMP
      cascade, but was not restricted to this signaling pathway, as phorbol myristate
      ester (TPA) and insulin also stimulated mRNA accumulation; (2) in contrast,
      powerful mitogens for thyroid cells, epidermal growth factor and hepatocyte
      growth factor, did not significantly modify ID3 mRNA levels; (3) ID3 protein
      levels closely parallelled mRNA levels, as revealed by immunofluorescence
      experiments showing a nuclear signal regulated by TSH; (4) in papillary thyroid
      carcinomas, ID3 mRNA was downregulated. Our results suggest that ID3 expression
      might be more related to the differentiating process induced by TSH than to the
      proliferative action of this hormone.

PMID- 12213215
TI  - The spindle pole body duplicates in early G1 phase in the pathogenic yeast
      Exophiala dermatitidis: an ultrastructural study.
AB  - The spindle pole body of the pathogenic yeast Exophiala dermatitidis was observed
      during the cell cycle using freeze-substitution and serial ultrathin sectioning
      electron microscopy. The spindle pole body was located on the outer membrane of
      the nuclear envelope and consisted of two disk elements connected by an
      intervening midpiece in G1 through G2 phases. Each disk element was composed of
      filamentous materials and measured 150 nm in diameter and 100 nm in thickness.
      The midpiece had higher electron density and measured 60 nm in length and 40 nm
      in thickness. At the beginning of prophase, each disk element of the spindle pole
      body enlarged to more than double in size. They were separated on the nuclear
      envelope, and associated with numerous cytoplasmic microtubules. At mitosis, the
      spindle pole body entered the nuclear envelope, associated with numerous nuclear
      microtubules, and was located at the spindle poles. At the end of telophase, it
      was extruded back into the cytoplasm from the nuclear envelope. Three-dimensional
      analysis of cells in different cell cycles suggested that duplication of the
      spindle pole body took place in early G1 phase. Thus, the location, structure,
      and duplication cycle of the E. dermatitidis spindle pole body were different
      from those of Saccharomyces cerevisiae.

PMID- 12213216
TI  - Activation of fatty acid synthesis during neoplastic transformation: role of
      mitogen-activated protein kinase and phosphatidylinositol 3-kinase.
AB  - Activation of fatty acid synthase (FAS) expression and fatty acid synthesis is a
      common event in tumor cells from a variety of human cancers and is closely linked
      to malignant transformation and to tumor virulence in population studies of human
      cancer. We now show that, in contrast to nutritional regulation of lipogenesis in
      liver or adipose tissue, changes in fatty acid metabolism during in vitro
      transformation of the human mammary epithelial cell line MCF-10a are driven by
      increases in epidermal growth factor signaling, acting in major part through the
      mitogen-activated protein (MAP) kinase and phosphatidylinositol (PI) 3-kinase
      signaling cascades. H-ras transformation of MCF-10a cells resulted in
      upregulation of MAP kinase and PI 3-kinase signals, upregulation of sterol
      regulatory element binding protein 1 (SREBP-1) transcription factor levels, and
      upregulation of FAS expression and FA synthesis. Deletion of the major SREBP
      binding site from the FAS promoter abrogated transcription in transformed MCF-10a
      cells. Inhibitors of MAP and PI 3-kinases downregulated SREBP-1 levels and
      decreased transcription from the FAS promoter, reducing FAS expression and fatty
      acid synthesis in transformed MCF-10a cells and in MCF-7 and HCT116 carcinoma
      cells. H-ras transformation sensitized MCF-10a cells to the FAS inhibitors
      cerulenin and C-75. These results confirm an important role for SREBP-1 in
      neoplastic lipogenesis, and provide a likely basis for the linkage of upregulated
      fatty acid metabolism with neoplastic transformation and with tumor virulence,
      since MAP and PI 3-kinase signaling contributes to both.

PMID- 12213217
TI  - Suppression of anchorage-independent growth of human cancer cell lines by the
      TRIF52/periostin/OSF-2 gene.
AB  - In searching for genes that suppress the viral transformation of primary cells,
      we have isolated a number of TRIF (transcript reduced in F2408) genes that are
      expressed well in primary rat embryo fibroblasts (REFs) but poorly in
      spontaneously immortalized rat fibroblast cell lines derived from REFs. One of
      these genes, TRIF52, is a rat homologue of the mouse protein periostin, which is
      suspected of being involved in oncogenesis. We found here that periostin mRNA
      expression is markedly downregulated in a variety of human cancer cell lines and
      human lung cancer tissues. Human cancer cell lines with reduced endogenous
      periostin gene expression that were infected with a recombinant retrovirus
      containing the periostin gene had reduced anchorage-independent growth.
      Mutational analysis revealed that the C-terminal region of periostin is
      sufficient to convey the anchorage-independent growth-suppressive activity of the
      protein. These observations together suggest that periostin may serve to inhibit
      the development of human cancers by acting as a tumor suppressor.

PMID- 12213218
TI  - Glucocorticoids modulate transformation by v-Src in a cell-specific manner.
AB  - In Balb 3T3 murine fibroblasts infected with retroviruses carrying the v-src
      oncogene, treatment with the glucocorticoid hormone dexamethasone induces a 10
      fold increase in the number of transformed foci and of anchorage-independent
      colonies. In contrast, in NIH-3T3-infected cells the number of foci and of
      colonies growing in soft agar is considerably reduced by the addition of the
      hormone. The effect of dexamethasone on both Balb 3T3 and NIH 3T3 cells is dose
      dependent and mediated by specific receptors. The expression of glucocorticoid
      receptors as well as transactivation of a mouse mammary tumor virus promoter in
      the presence of dexamethasone is comparable in the two cell lines. Dexamethasone
      does not change the expression and kinase activity of v-Src proteins either in
      freshly infected Balb 3T3 and NIH 3T3 cells or in morphologically normal clones
      or in transformed foci derived from infected Balb 3T3 cells stably expressing v
      Src. However, in cocultivation assays of phenotypically normal clones of v-Src
      expressing Balb 3T3 cells mixed with a large excess of parental Balb 3T3 cells,
      the hormone is able to rescue the ability to form transformed foci of these
      otherwise normal cells. The present data point out a new role of glucocorticoid
      hormones in controlling transformation in a cell-specific manner through
      epigenetic mechanisms.

PMID- 12213219
TI  - Coiled body heterogeneity induced by G(1) arrest with amiloride + bumetanide.
AB  - Ki67 is a nuclear protein expressed in proliferating cells, but not in quiescent
      or G(0)-arrested cells. Similar to the proliferating cell nuclear antigen and
      several other well-characterized molecules, Ki67 exhibits a repeating pattern of
      regulated expression and redistribution during the cell cycle, making it a useful
      marker for cell cycle phase. In addition to other structures labeled,
      concentrated foci may be observed in the nucleus and sometimes the cytoplasm. We
      observed that these Ki67 foci can be found at any stage of the endothelial cell
      cycle. They are not coincident with coiled bodies (CB), as determined in double
      label immunofluorescence experiments with anti-Ki67 and antibodies to the CB
      marker protein pigpen. However, arrest of BPA47 endothelial cells in G(1) with
      amiloride + bumetanide induces colocalization of pigpen and Ki67 in 40% of cells
      exhibiting Ki67 foci. We conducted a series of experiments to examine the
      possibilities that pigpen was exported from CB and into unique, Ki67-containing
      foci or that Ki67 was imported into pigpen-containing CB. Our results showed us
      that although CB typically contain both coilin and pigpen, amiloride + bumetanide
      induced G(1) arrest reconfigured the CB compartment into three populations of
      foci: one containing pigpen without coilin, the second containing coilin without
      pigpen, and a third containing both pigpen and coilin together. Furthermore, G(1)
      arrest resulted in Ki67 redistribution into both coilin- and pigpen-containing
      foci. The results suggest that under certain conditions, "resident" CB proteins
      can be differentially redistributed, and proteins not previously recognized as
      resident in CB can be driven into that compartment. Our observations underscore
      the fluid nature of CB. They demonstrate that previously reported heterogeneity
      in the CB compartment can be amplified by a specific experimental manipulation.
      This may be useful in future analyses of protein trafficking within the CB
      compartment and between CB and other cellular compartments. Finally, the
      redistribution of Ki67 into CB represents a new finding for a widely expressed
      but poorly understood molecule, one that may be useful in elucidating function.

PMID- 12213220
TI  - Induction of EGF-dependent apoptosis by vacuolar-type H(+)-ATPase inhibitors in
      A431 cells overexpressing the EGF receptor.
AB  - The stimulation of human tumor cells overexpressing epidermal growth factor
      receptor (EGFR) with EGF enhances tumor development and malignancy. Therefore,
      compounds that modulate the EGF-mediated signal inducing apoptosis in EGFR
      overexpressing cells would represent a new class of antitumor drug and might be
      useful in the treatment of a subset of human tumors. In the course of screening
      for compounds that induce apoptosis in EGFR-overexpressing human epidermal
      carcinoma A431 cells from secondary metabolites of microorganisms, we found that
      vacuolar-type H(+)-ATPase (V-ATPase) inhibitors, such as concanamycin B and
      destruxin E, induced apoptosis only when the cells were stimulated with EGF. The
      EGF-dependent apoptosis by V-ATPase inhibitors was not observed in other types of
      human tumor cells which do not overexpress EGFR. The apoptosis in A431 cells was
      inhibited by anti-FasL antibody which neutralized the cytotoxic effect of FasL,
      indicating that the Fas/FasL system was involved. The expression of cell surface
      FasL was upregulated by stimulation with EGF and increased further by V-ATPase
      inhibitors. Moreover, EGF inhibited cytotoxic Fas antibody-induced apoptosis,
      whereas V-ATPase inhibitors disrupted the protective effect of EGF on apoptosis
      in A431 cells. Taken together, these results suggested that V-ATPase inhibitors
      induced EGF-dependent apoptosis in A431 cells, possibly through both the
      enhancement of EGF-induced cell surface expression of FasL and the disruption of
      an EGF-induced survival signal.

PMID- 12213221
TI  - Distinct patterns of mitochondrial changes precede induction of apoptosis by all
      trans-retinoic acid and N-(4-hydroxyphenyl)retinamide in MCF7 breast cancer
      cells.
AB  - The biochemical mechanisms of apoptosis-induction by all-trans-retinoic acid
      (atRA) and N-(4-hydroxyphenyl)retinamide (4HPR) in cultured MCF7 cancer cells
      were studied by multiparameter flow cytometry. Retinoid treatment induced
      formation of two biochemically distinct cell subpopulations, which preceded the
      appearance of cells with fragmented nuclei. Exposure to atRA led to a transient
      increase in NADH level and mitochondrial oxidative turnover and a slow decline in
      reduced thiol level and mitochondrial membrane potential, suggesting that atRA
      treatment induces a transient defense mechanism. The synthetic retinoid 4HPR, in
      contrast, caused a gradual decrease in mitochondrial oxidative turnover and
      cardiolipin level together with a small decline in mitochondrial membrane
      potential, suggesting that 4HPR induces oxidation of cardiolipin and subsequent
      leakage of the mitochondria. Co-incubation with cyclosporin A, an inhibitor of
      the mitochondrial permeability transition, did not prevent formation of
      fragmented nuclei or induction of changes in mitochondrial parameters by
      retinoids. Thus, the mitochondrial permeability transition does not appear to be
      involved in retinoid induction of apoptosis in MCF7 cells. Retinoid exposure of
      diploid human mammary epithelial cells induced mild oxidative stress but did not
      lead to formation of two cell subpopulations. We conclude that atRA and 4HPR
      induce apoptosis in MCF7 cells by two distinct and novel biochemical mechanisms.

PMID- 12213222
TI  - CD4 is active as a signaling molecule on the human monocytic cell line Thp-1.
AB  - CD4 is a 56-kDa membrane glycoprotein expressed by a subset of T cells, by cells
      of the monocyte/macrophage lineage, and by eosinophils and dendritic cells. CD4
      serves as a coreceptor for HIV and IL-16. T cell CD4 mediates signal transduction
      by associating with the protein tyrosine kinase p56(lck); this interaction does
      not exist in monocytes. We wished to elucidate the mechanism(s) by which monocyte
      CD4 transduces signals. Stimulation of CD4 on Thp-1 monocytic cells induced a
      Ca(2+) flux and the time-dependent activation of phosphotyrosine proteins ranging
      from 35 to 180 kDa. We identified the 140- and 85-kDa proteins as phospholipase C
      gamma (PLC-gamma) and the regulatory subunit of phosphatidylinositol 3-kinase (PI
      3K), respectively. Using immunoprecipitation/Western immunoblotting however, we
      were unable to show any direct association between CD4 and PLC-gamma, PI-3K, or
      other known signaling proteins. To identify proteins capable of associating with
      the cytoplasmic tail of CD4, we fused it with gluthatione S-transferase and used
      the fusion protein in far Western and pull-down experiments. In both types of
      experiments, the fusion protein routinely associated with 45- and 55-kDa
      proteins. Mass spectrometry analysis of the tryptic peptides generated from these
      two proteins indicated novel sequences.

PMID- 12213223
TI  - A role for the de novo sphingolipids in apoptosis of photosensitized cells.
AB  - Sphingolipids have been implicated in apoptosis after various stress inducers. To
      assess the involvement of the de novo sphingolipid pathway in apoptosis,
      photodynamic therapy (PDT) with the photosensitizer Pc 4 was used as a novel
      stress inducer. Here we provide biochemical and genetic evidence of the role of
      the de novo sphingolipids in apoptosis post-Pc 4-PDT. In Jurkat cells PDT-induced
      intracellular sphinganine accumulation, DEVDase activation, PARP cleavage, and
      apoptosis were suppressed by the de novo sphingolipid synthesis inhibitor ISP-1
      (Myriocin). Coincubation with sphinganine, sphingosine, or C16-ceramide
      specifically reversed the antiapoptotic actions of ISP-1 or the singlet oxygen
      scavenger L-histidine. PDT-induced cytochrome c release from mitochondria into
      the cytosol was inhibited by L-histidine, but not by ISP-1. Cotreatment with
      sphinganine did not reverse the inhibitory effect of L-histidine. In addition,
      PDT-induced sphinganine accumulation and apoptosis were ISP-1-sensitive in A431
      human epidermoid and HT29 human carcinoma cells. Furthermore, in LY-B cells, CHO
      derived mutants deficient in the de novo sphingolipid synthesis enzyme serine
      palmitoyltransferase (SPT) activity, DEVDase activation and apoptosis were
      delayed and suppressed post-PDT. Hence, the data are consistent with the partial
      involvement of the de novo sphingolipid pathway in apoptosis via DEVDase
      activation downstream of mitochondrial cytochrome c release post-Pc 4-PDT.

PMID- 12213224
TI  - Ethanol sensitivity of NMDA receptors.
AB  - NMDA receptors are ionotropic glutamate receptors assembled of subunits of the
      NR1 and of the NR2 family (NR2A-NR2D). The subunit diversity largely affects the
      pharmacological properties of NMDA receptors and, hence, gives rise to receptor
      heterogeneity. As an overall result of studies on recombinant and native NMDA
      receptors, ethanol inhibits the function of receptors containing the subunits
      NR2A and/or NR2B to a greater extent than those containing NR2C or NR2D. For
      example, in rat cultured mesencephalic neurons, NR2C expression was
      developmentally increased, whereas expression of NR2A and NR2B was decreased.
      These changes coincided with a developmental loss of sensitivity of NMDA
      responses to ethanol and ifenprodil, a non-competitive NMDA receptor antagonist
      that shows selectivity for NR2B-containing receptors. Also in rat locus coeruleus
      neurons, the low ethanol sensitivity of somatic NMDA receptors could be explained
      by a prominent expression of NR2C. The inhibitory site of action for ethanol on
      the NMDA receptor is not yet known. Patch-clamp studies suggest a target site
      exposed to or only accessible from the extracellular environment. Apparently,
      amino acid residue Phe(639), located in the TM3 domain of NR1, plays a crucial
      role in the inhibition of NMDA receptor function by ethanol. Since this
      phenylalanine site is common to all NMDA and non-NMDA receptor (AMPA/kainate
      receptor) subunits, this observation is consistent with accumulating evidence for
      a similar ethanol sensitivity of a variety of NMDA and non-NMDA receptors, but it
      cannot explain the differences in ethanol sensitivity observed with different NR2
      subunits.

PMID- 12213225
TI  - Chaperones and aging: role in neurodegeneration and in other civilizational
      diseases.
AB  - Chaperones are highly conserved proteins responsible for the preservation and
      repair of the correct conformation of cellular macromolecules, such as proteins,
      RNAs, etc. Environmental stress leads to chaperone (heat-shock protein, stress
      protein) induction reflecting the protective role of chaperones as a key factor
      for cell survival and in repairing cellular damage after stress. The present
      review summarizes our current knowledge about the chaperone-deficiency in the
      aging process, as well as the possible involvement of chaperones in
      neurodegenerative diseases, such as in Alzheimer's, Parkinson's, Huntington- and
      prion-related diseases. We also summarize a recent theory implying chaperones as
      "buffers" of variations in the human genome, which role probably increased during
      the last 200 years of successful medical practice minimizing natural selection.
      Chaperone-buffered, silent mutations may be activated during the aging process,
      which leads to the phenotypic exposure of previously hidden features and might
      contribute to the onset of polygenic diseases, such as atherosclerosis, cancer,
      diabetes and several neurodegenerative diseases.

PMID- 12213226
TI  - Toluene inhibits voltage-sensitive calcium channels expressed in pheochromocytoma
      cells.
AB  - Commercial solvents such as toluene are commonly used as drugs of abuse by
      children and adolescents. The cellular and molecular sites and mechanisms of
      actions of these compounds are not well studied but their effects on behavior
      resemble those of central nervous system depressants such as alcohol,
      barbiturates and benzodiazepines. In this study, the effects of toluene on
      voltage-sensitive calcium channels (VSCCs) were measured in pheochromocytoma
      cells. The KCl-induced rise in intracellular calcium as measured by calcium
      imaging was almost completely blocked by the dihydropyridine calcium channel
      antagonist nifedipine verifying that undifferentiated pheochromocytoma cells
      express mainly the L-type of calcium channel. Toluene (0.3-3000 microM) by itself
      did not affect intracellular calcium levels in resting cells but dose-dependently
      inhibited the KCl-induced rise in calcium. This inhibition was substantially
      reversed upon washout of the toluene-containing solution. KCl-dependent increases
      in intracellular calcium in cells differentiated with nerve growth factor (NGF)
      were largely insensitive to nifedipine. Toluene produced a greater inhibition of
      the KCl response in NGF treated cells as compared with undifferentiated cells. A
      similar finding was obtained when whole-cell patch-clamp-electrophysiology was
      used to directly monitor the effects of toluene on voltage-activated calcium
      currents in undifferentiated and differentiated cells. These results show that
      dihydropyridine sensitive and insensitive calcium channels are inhibited by
      toluene and may represent important sites of action for this compound.

PMID- 12213227
TI  - Stimulation of peripheral nociceptor endings by low dose morphine and its
      signaling mechanism.
AB  - In this report, we demonstrated that peripheral application of very low dose
      (amol ranges) of morphine induced flexor response through a substance P (SP)
      release at the nociceptor endings in mice. The intraplantar (i.pl.) application
      of morphine produced flexor response in a dose-dependent manner from 0.1 to
      1000amol. The mu-opioid receptor (MOP-R) agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]
      enkephalin (DAMGO) also produced dose-dependent flexor response in same dose
      ranges. Morphine-induced flexor responses were markedly inhibited by naloxone and
      D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP) both MOP-R antagonists and by
      intrathecal injection of antisense oligodeoxynucleotide (AS-ODN) for MOP-R which
      is expected to reduce the receptor expression in sensory nerve endings. Prior
      incubation with capsaicin, a depletor of SP from polymodal C fibers and [(+)
      (2S,3S)-(2-methoxybenzylamino)-2-phenylpiperidine] (CP-99994), a tachykinin 1
      receptor antagonist, also blocked the morphine-induced flexor responses.
      Moreover, pertussis toxin (PTX) which inactivates G(alpha)(i/o); [(1-[6-([(17b)-3
      methoxyestra-1,3,5(10)-trien-17-yl]amino)hexyl]-1H-pyrrole-2,5-dione)] (U-73122),
      an inhibitor of phospholipase C (PLC); ethyleneglycol-bis(beta-aminoethyl ether)
      N,N,N',N'-tetraacetic acid (EGTA), a Ca(2+) chelating agent; xestospongin C, a
      membrane-permeable inositol trisphosphate (InsP(3)) receptor antagonist inhibited
      the morphine-flexor responses. However, thapsigargin, a depletor of intracellular
      Ca(2+) concentration and diphenhydramine, a histamine (His) H1 receptor
      antagonist, were unable to block the morphine-induced flexor responses. These
      results suggest that extremely low doses of morphine can stimulate sensory nerve
      endings through activation of peripheral MOP-R and its downstream mechanisms
      include activation of PLC through a SP release from polymodal C fibers.

PMID- 12213228
TI  - Human amyloid-beta causes changes in the levels of endothelial protein kinase C
      and its alpha isoform in vitro.
AB  - Amyloid-beta (A(beta)) deposits and neurofibrillary pathology are characteristic
      features of Alzheimer's disease (AD). The association of A(beta) with cerebral
      vessels is an intriguing feature of AD. While there is considerable evidence of
      altered activities of the major isoforms of protein kinase C (PKC) in the
      vasculature and neurons of AD brains, little is known about the relationship
      between the Abeta toxicity and the altered PKC levels in cerebral endothelial
      cells. In this study, cultured brain endothelial cells exposed to A(beta)1-40
      revealed a translocation of PKC from the membrane fraction to the cytosol. The
      content of the isoform PKC(alpha), involved in the regulation of amyloid
      precursor protein (APP) secretion, was decreased in the membrane-bound fraction
      of rat endothelial cells and increased in the cytosol after A(beta)1-40
      treatment. These data suggest that the accumulation of A(beta) peptide in the
      cerebral vasculature may play a significant role in the down-regulation of PKC
      seen in the AD cerebral vasculature.

PMID- 12213229
TI  - Cocaine regulates TRH-related peptides in rat brain.
AB  - Cocaine administration has previously been reported to alter the levels of prepro
      TRH mRNA and TRH (pGlu-His-Pro-NH(2)) in the limbic system of rats (J. Neurochem.
      60 (1993) 1151). We have now demonstrated that a previously unrecognized family
      of TRH-like peptides is involved in the actions of cocaine. We treated young
      adult male Sprague-Dawley rats (five per group, 250g body weight at sacrifice)
      for 2 weeks with either twice daily injections of saline (control group), twice
      daily injections of 15mg/kg cocaine until sacrifice (chronic group), single
      injection of 15mg/kg cocaine 2h prior to sacrifice (acute group) or chronic
      cocaine injections replaced by saline injections 72h prior to sacrifice
      (withdrawal group (WD)). Twelve different brain regions were dissected and
      immunoreactivity for TRH (TRH-IR), EEP (pGlu-Glu-Pro-NH(2); EEP-IR) and related
      peptides were measured by radioimmunoassay (RIA). High pressure liquid
      chromatography (HPLC) revealed that in many brain regions EEP-IR and TRH-IR
      consisted of a mixture of TRH, and other TRH-like peptides including EEP, pGlu
      Val-Pro-NH(2) (Val(2)-TRH), pGlu-Tyr-Pro-NH(2) (Tyr(2)-TRH), pGlu-Leu-Pro-NH(2)
      (Leu(2)-TRH), and pGlu-Phe-Pro-NH(2) (Phe(2)-TRH). Following i.p. injection,
      these TRH-like peptides readily crossed the blood-brain barrier but cleared very
      slowly from brain tissues. Acute cocaine produced a 4.1-fold increase in Val(2)
      TRH level in medulla while Val(2)-TRH and Tyr(2)-TRH, increased 6.2- and 2.9
      fold, respectively in pyriform cortex PYR. TRH and Leu(2)-TRH, decreased 47 and
      93%, respectively in the nucleus accumbens (AM) while other EEP-IR peaks
      decreased 50-100% consistent with the significant decrease in total EEP-IR in the
      AMs following acute cocaine treatment. Because 2h is too short a time to alter
      levels of neuropeptides via changes in the rate of biosynthesis, the acute
      cocaine-induced elevation or reduction in TRH and related peptides is most likely
      due to suppression or stimulation, respectively, of the corresponding peptide
      secretion rate. Because TRH and TRH-like peptides have antidepressant, analeptic
      and euphorigenic properties, we conclude that these endogenous substances are
      potential mediators of both the cocaine "high" and withdrawal symptoms.

PMID- 12213230
TI  - Presenilin-1 and the amyloid precursor protein are transported bidirectionally in
      the sciatic nerve of adult rat.
AB  - The amyloid precursor protein (APP) and presenilin-1 (PS-1) are not only of
      importance for the normal functioning of the various neurons, but also play
      central roles in the pathogenesis of Alzheimer's disease (AD). Through the use of
      immunohistochemical and Western blot techniques, the bidirectional axonal
      transport of these proteins has been demonstrated in the sciatic nerve of adult
      rat. Double-ligation of the sciatic nerve for 6, 12 or 24h was observed to cause
      a progressive accumulation of the 45kDa presenilin-1 holoprotein and APPs with
      molecular masses of 116 and 94kDa on both sites of the ligature. It is concluded
      that the functions of presenilin-1 and APPs are not restricted to the neuronal
      perikarya: they may carry information in both directions, from the cell body to
      the axon terminals and vice versa.

PMID- 12213231
TI  - Evolution and phylogenetic information content of the ribosomal DNA repeat unit
      in the Blattodea (Insecta).
AB  - The organization, structure, and nucleotide variability of the ribosomal repeat
      unit was compared among families, genera, and species of cockroaches
      (Insecta:Blattodea). Sequence comparisons and molecular phylogenetic analyses
      were used to describe rDNA repeat unit variation at differing taxonomic levels. A
      reverse similar 1200 bp fragment of the 28S rDNA sequence was assessed for its
      potential utility in reconstructing higher-level phylogenetic relationships in
      cockroaches. Parsimony and maximum likelihood analyses of these data strongly
      support the expected pattern of relationships among cockroach groups. The
      examined 5' end of the 28S rDNA is shown to be an informative marker for larger
      studies of cockroach phylogeny. Comparative analysis of the nucleotide sequences
      of the rDNA internal transcribed spacers (ITS1 and ITS2) among closely related
      species of Blattella and Periplaneta reveals that ITS sequences can vary widely
      in primary sequence, length, and folding pattern. Secondary structure estimates
      for the ITS region of Blattella species indicate that variation in this spacer
      region can also influence the folding pattern of the 5.8S subunit. These results
      support the idea that ITS sequences play an important role in the stability and
      function of the rRNA cluster.

PMID- 12213232
TI  - Acyl-CoA Z9- and Z10-desaturase genes from a New Zealand leafroller moth species,
      Planotortrix octo.
AB  - Two cDNAs encoding acyl-CoA Z9-desaturase from the fat body and Z10-desaturase
      from the pheromone gland of the greenhead leafroller moth, Planotortrix octo,
      were obtained by RACE PCR. The Z9-desaturase (Pocto-Z9) cDNA spans 2291 nt with
      an ORF encoding a 352 amino-acid protein, which has 65% identity to Trichoplusia
      ni Delta 9 desaturase (Tni-Z9). The Z10-desaturase (Pocto-Z10) cDNA spans 2777 nt
      with an ORF encoding a protein with 356 amino acids. Pocto-Z10 shows lower
      identity to Pocto-Z9 and Tni-Z9 (48 and 46%, respectively) and relatively higher
      identity to the Delta 11 desaturases of T. ni and Helicoverpa zea (57 and 56%,
      respectively). The ORFs of these two P. octo cDNAs were constructed into an
      expression vector, YEpOLEX, that complemented the unsaturated fatty acid (UFA)
      auxotrophy of a desaturase-deficient ole1 strain of Saccharomyces cerevisiae.
      Expression of Pocto-Z9 produced a 5:2 ratio of Z9-16 and Z9-18 acids, with minor
      amounts (<4%) of Z9-14, Z9-15, and Z9-17 acids. Pocto-Z10 was successfully
      expressed in the YEpOLEX system when complemented with Z11-18:Me, and the major
      desaturase product proved to be Z10-16:Acid. The results confirm the regio- and
      stereo-selectivity of this unusual Delta 10 desaturase.

PMID- 12213233
TI  - Putative protein digestion in a sap-sucking homopteran plant pest (rice brown
      plant hopper; Nilaparvata lugens: Delphacidae)--identification of trypsin-like
      and cathepsin B-like proteases.
AB  - Sap-sucking phytophagous insect species of the order Hemiptera have been assumed
      not to carry out digestive proteolysis, but instead to rely on free amino acids
      in the phloem and xylem saps for their nutritional requirements. Extracts
      prepared from isolated guts of rice brown planthopper (Nilaparvata lugens), a
      homopteran crop pest, were shown to contain protease activity, with hydrolysis of
      both protein and synthetic peptide substrates being observed. Assays with
      specific inhibitors suggested that a trypsin-like serine protease was responsible
      for most of hydrolytic activity against synthetic substrates. A cDNA library was
      prepared from RNA extracted from N. lugens gut tissue, and screened for protease
      encoding sequences. cDNAs for a cathepsin B-like protease and a trypsin-like
      protease were isolated and fully characterised; the latter exhibits a novel C
      terminal region and an unusual activation mechanism, and represents a small gene
      family. Soya bean Kunitz trypsin inhibitor (SKTI) is an effective inhibitor of
      protein hydrolysis by N. lugens gut extracts in vitro, explaining why transgenic
      rice plants expressing this protein are partially resistant to the insect (Mol.
      Breed. 5 (1999) 1). It is suggested that digestive proteolysis may be widespread
      in sap-sucking homoptera, and can make a significant contribution to nutrition.

PMID- 12213234
TI  - Cloning and functional expression of a fat body-specific chitinase cDNA from the
      tsetse fly, Glossina morsitans morsitans.
AB  - A chitinase cDNA, GChit1 was isolated from Glossina morsitans morsitans and shown
      to be specifically expressed in fat body tissue. GChit1 is encoded by a 1.6 kb
      mRNA with a putative open reading frame (ORF) of 460 amino acids (predicted
      pI=7.5, m.w.=51kDa) that contains a signal peptide domain and two potential N
      linked glycosylation sites. The ORF exhibits homology to various chitinases
      characterized from insects. It has the conserved catalytic site residues and the
      cysteine-rich 3'-end domain associated with chitin binding although the
      serine/threonine rich domain is apparently missing. Southern blot data indicate
      that GChit1 is present as a single-copy locus in the Glossina genome. Northern
      analysis indicates that transcripts for GChit1 can be detected only from the fat
      body of adult flies. Similarly, chitinase activity could be detected in fat body
      but not in the gut or salivary gland tissues. The full-length cDNA was expressed
      in vitro in Drosophila S2 cells and the molecule was produced in a soluble form.
      Polyclonal antibodies raised against recGChit1 could recognize a protein of about
      50 kDa in adult fat body extracts. In addition to fat body, chitinase protein was
      detected by Western analysis from the milk gland tissue of pregnant females as
      well as from the intrauterine larval and pupal developmental stages. No chitinase
      specific mRNA transcripts could be observed, however from larvae and pupae. The
      intrauterine larva of tsetse may receive the protein from its mother via the milk
      gland route. The molecular characteristics of GChit and its product and the
      potential role of this chitinase in tsetse biology are discussed.

PMID- 12213235
TI  - Infestin, a thrombin inhibitor presents in Triatoma infestans midgut, a Chagas'
      disease vector: gene cloning, expression and characterization of the inhibitor.
AB  - This work describes the purification, gene cloning and expression of infestin, a
      thrombin inhibitor from midguts of Triatoma infestans. Infestin is located in the
      midgut and its purification was performed by anion-exchange and affinity
      chromatographies. The N-terminal sequence and the sequence of tryptic peptides
      were determined. Using RT-PCR, total RNA and infestin cDNA information, a DNA
      fragment was cloned which encodes a multi non-classical Kazal-type serine
      protease inhibitor. Isolated native infestin has two non-classical Kazal-type
      domains and shows an apparent molecular mass of 13 kDa, while its gene codes for
      a protein with four non-classical Kazal-type domains corresponding to an apparent
      molecular mass of 22 kDa. Two recombinant infestins, r-infestin 1-2 and r
      infestin 1-4, were constructed using the vector pVT102U/alpha and expressed in S.
      cerevisiae. Native and r-infestin 1-2 showed very similar inhibitory activities
      towards thrombin and trypsin with dissociation constants of 43.5 and 25 pM for
      thrombin and 2.0 and 3.1 nM for trypsin, respectively. No other serine protease
      of the blood coagulation cascade was inhibited by the r-infestin 1-2.
      Surprisingly, r-infestin 1-4 inhibited not only thrombin and trypsin (K(i) of 0.8
      and 5.2 nM, respectively), but also factor XIIa, factor Xa and plasmin (K(i) of
      78 pM, 59.2 and 1.1 nM, respectively).

PMID- 12213236
TI  - Molecular cloning, expression analysis and functional confirmation of two
      ecdysone receptor isoforms from the rice stem borer Chilo suppressalis.
AB  - PCR techniques were used to clone and identify cDNAs for ecdysone receptor A and
      B1 (EcR-A and EcR-B1) isoforms from the rice stem borer, Chilo suppressalis. They
      differ only in the N-terminal A/B regions and show high sequence identities to
      other insects' EcRs. At the wandering stage, EcR-B1 mRNA was expressed more
      abundantly in the midgut than in the epidermis and fat body, whereas expression
      levels of EcR-A mRNA were similar in the three tissues. In the epidermis of the
      last instar larvae, the maximal mRNA expression of both EcR-A and EcR-B1 was
      observed from the wandering to prepupal stages prior to the peak of ecdysteroid
      titer in the hemolymph. In gel mobility shift assays, in vitro translated C.
      suppressalis EcR-B1 (CsEcR-B1) and Bombyx mori ultraspiracle (BmUSP) proteins
      bound to the Pal 1 and Drosophila melanogaster hsp27 ecdysone response element as
      a heterodimer. These results indicate that the cDNAs isolated here encode
      functional ecdysone receptors.

PMID- 12213237
TI  - Allele frequency and gene expression of a putative carboxylesterase-encoding gene
      in a pyrethroid resistant strain of the tick Boophilus microplus.
AB  - We utilized RNA Northern blot analysis and ribonuclease protection assays (RPA)
      to study the mRNA expression level of a putative carboxylesterase-encoding gene
      from several strains of Boophilus microplus (Canestrini). Both the Northern
      analysis and RPAs indicated that an esterase transcript was more abundant in the
      pyrethroid resistant strain, Coatzacoalcos (Cz), compared to a susceptible
      control strain and a resistant strain whose pyrethroid resistance is mediated
      through a target site insensitivity mechanism. A PCR-based assay was designed to
      identify the presence of a previously reported point mutation in this B.
      microplus esterase gene. The reported G-->A substitution at nucleotide 1120
      creates an EcoR I site in the mutant allele which can be detected by EcoR I
      digestion of the amplification products. The PCR assays showed that the frequency
      of the mutant allele was highest in the Cz-resistant strain, which has been shown
      to have an esterase-mediated resistance mechanism. The PCR assay can be performed
      either on individual tick larvae or hemolymph from adults.

PMID- 12213238
TI  - In vitro production of adaline and coccinelline, two defensive alkaloids from
      ladybird beetles (Coleoptera: Coccinellidae).
AB  - In vitro experiments using [1-(14)C] and [2-(14)C]acetate were devised to study
      the biosynthesis of the defensive coccinellid alkaloids adaline and coccinelline
      in Adalia 2-punctata and Coccinella 7-punctata, respectively. The labelled
      alkaloids obtained in these experiments had a specific activity about ten times
      higher than that of the samples obtained in feeding experiments. This in vitro
      assay has enabled us to demonstrate that these two alkaloids are most likely
      biosynthesised through a fatty acid rather than a polyketide pathway, that
      glutamine is the preferred source of the nitrogen atom and that alkaloid
      biosynthesis takes place in the insect fat body.

PMID- 12213239
TI  - Cry1A toxins of Bacillus thuringiensis bind specifically to a region adjacent to
      the membrane-proximal extracellular domain of BT-R(1) in Manduca sexta:
      involvement of a cadherin in the entomopathogenicity of Bacillus thuringiensis.
AB  - Many subspecies of the soil bacterium Bacillus thuringiensis produce various
      parasporal crystal proteins, also known as Cry toxins, that exhibit insecticidal
      activity upon binding to specific receptors in the midgut of susceptible insects.
      One such receptor, BT-R(1) (210 kDa), is a cadherin located in the midgut
      epithelium of the tobacco hornworm, Manduca sexta. It has a high binding affinity
      (K(d) approximately 1nM) for the Cry1A toxins of B. thuringiensis. Truncation
      analysis of BT-R(1) revealed that the only fragment capable of binding the Cry1A
      toxins of B. thuringiensis was a contiguous 169-amino acid sequence adjacent to
      the membrane-proximal extracellular domain. The purified toxin-binding fragment
      acted as an antagonist to Cry1Ab toxin by blocking the binding of toxin to the
      tobacco hornworm midgut and inhibiting insecticidal action. Exogenous Cry1Ab
      toxin bound to intact COS-7 cells expressing BT-R(1) cDNA, subsequently killing
      the cells. Recruitment of BT-R(1) by B. thuringiensis indicates that the
      bacterium interacts with a specific cell adhesion molecule during its
      pathogenesis. Apparently, Cry toxins, like other bacterial toxins, attack
      epithelial barriers by targeting cell adhesion molecules within susceptible
      insect hosts.

PMID- 12213241
TI  - Identification of major soluble salivary gland proteins in teneral Glossina
      morsitans morsitans.
AB  - Salivary glands of tsetse flies (Diptera: Glossinidiae) contain molecules that
      are involved in preventing blood clotting during feeding as well as molecules
      thought to be intimately associated with trypanosome development and maturation.
      Here we present a protein microchemical analysis of the major soluble proteins of
      the salivary glands of Glossina morsitans morsitans, an important vector of
      African trypanosomes. Differential solubilization of salivary proteins was
      followed by reverse-phase, high-performance liquid chromatography (HPLC) and
      analysis of fractions by 1-D gel electrophoresis to reveal four major proteins.
      Each protein was subjected to amino acid microanalysis and N-terminal
      microsequencing. A protein chemical approach using high-resolution 2-D gel
      electrophoresis and mass spectrometry was also used to identify the salivary
      proteins. Matrix-assisted, laser desorption ionization time-of-flight (MALDI-TOF)
      mass spectrometry and quadrupole time-of-flight (Q-TOF) tandem mass spectrometry
      methods were used for peptide mass mapping and sequencing, respectively. Sequence
      information and peptide mass maps queried against the NCBI non-redundant database
      confirmed the identity of the first protein as tsetse salivary gland growth
      factor-1 (TSGF-1). Two proteins with no known function were identified as tsetse
      salivary gland protein 1 (Tsal 1) and tsetse salivary gland protein 2 (Tsal 2).
      The fourth protein was identified as Tsetse antigen-5 (TAg-5), which is a member
      of a large family of anti-haemostatic proteins. The results show that these four
      proteins are the most abundant soluble gene products present in salivary glands
      of teneral G. m. morsitans. We discuss the possible functions of these major
      proteins in cyclical transmission of African trypanosomes.

PMID- 12213240
TI  - Ribonucleotide reductase subunits from the yellow fever mosquito, Aedes aegypti:
      cloning and expression.
AB  - Ribonucleotide reductase catalyses the de novo synthesis of deoxyribonucleotides.
      Class I reductases use an iron center to generate a tyrosyl free radical that can
      initiate formation of the deoxyribonucleotide. These reductases are alpha 2 beta
      2 holoenzymes, and the subunits are denoted as R1 and R2. R1 contains the
      allosteric binding site and the active site, whereas R2 contains a binuclear iron
      center that initiates formation of the tyrosyl radical. We have cloned and
      sequenced the cDNAs encoding the R1 and R2 subunit in the yellow fever mosquito,
      Aedes aegypti. The messages for these proteins are increased in response to blood
      feeding.

PMID- 12213242
TI  - Cultured Aedes albopictus mosquito cells accumulate elongation factor-1 alpha (EF
      1 alpha) during serum starvation.
AB  - We examined survival, growth and protein synthesis in mosquito cells that had
      been maintained for up to 21 days in serum-free medium. On polyacrylamide gels,
      protein bands from "starved" cells remained discrete, and despite low levels of
      incorporation, radiolabeled bands were detectable, suggesting that low levels of
      protein synthesis were sustained. A prominent band that accumulated in serum
      starved cells was digested with trypsin and analyzed by tandem mass spectrometry,
      which identified the protein as eukaryotic elongation factor (EF)-1 alpha EF-1
      alpha is well-conserved among species, and differential accumulation of EF-1
      alpha in serum-starved cells was verified by western blotting using a primary
      antibody to the homologous protein from Trypanosoma brucei. Aside from its
      importance in the elongation step of protein synthesis, EF-1 alpha has been shown
      to have a number of non-canonical functions, including interaction with viral RNA
      and a potential role in apoptosis. We anticipate that the prolonged viability of
      mosquito cells in serum-free medium may provide a system to explore whether EF-1
      alpha accumulation is an adaptive response compatible with resumption of growth
      in the event that nutrients are replenished, or whether the excess EF-1 alpha
      represents an irreversible commitment to an apoptotic pathway.

PMID- 12213243
TI  - cDNA cloning of a salivary chymotrypsin-like protease and the identification of
      six additional cDNAs encoding putative digestive proteases from the green mirid,
      Creontiades dilutus (Hemiptera: Miridae).
AB  - RT-PCR with degenerate primers was used to amplify partial cDNA fragments for one
      serine protease gene and three cysteine protease genes from poly(A) RNA isolated
      from the midgut of the green mirid, Creontiades dilutus. The serine protease
      amplicon showed homology to insect trypsin-like protease genes, and all three
      cysteine protease amplicons showed homology to cathepsin L-like protease genes.RT
      PCR was also used to amplify fragments of three serine protease genes from
      salivary gland poly(A) RNA. One of these salivary gland serine protease amplicons
      was used to screen a whole organism cDNA library to isolate a full length cDNA
      clone, designated CdSp1 (Accession AY055753), which encodes a putative
      chymotrypsin-like protease. CdSp1 codes for a 293 amino acid protein that
      contains a signal peptide and activation peptide, as well as the catalytic triad
      present in all serine proteases and several of the binding pocket residues
      characteristic of chymotrypsins. In situ hybridisation showed that the transcript
      is expressed in the posterior lobe of the principal salivary gland, but not in
      the anterior lobe of the principal salivary gland, the accessory salivary gland
      or the midgut.

PMID- 12213244
TI  - Characteristic properties of proteins from pre-ecdysial cuticle of larvae and
      pupae of the mealworm Tenebrio molitor.
AB  - Proteins extracted from the cuticle of pharate larvae and pupae of the mealworm
      Tenebrio molitor are more soluble at low temperatures than at higher
      temperatures, a behaviour characteristic of hydrophobic proteins. When the
      temperature of an unfractionated cuticular extract is raised from 4 to 25 degrees
      C the solution becomes turbid, droplets of a heavy, protein-rich phase are
      formed, which gradually settles, leaving an upper protein-poor phase, indicating
      that the aggregation process is a coacervation. The aggregation of the dissolved
      cuticular proteins is influenced by changes in temperature, pH, and ionic
      strength. The process has been studied by measuring development of turbidity in
      unfractionated cuticular extracts and in solutions of three purified proteins
      from Tenebrio pharate larvae and pupae (TmLPCP-A1a, TmLPCP-E1a, and TmLPCP-G1a),
      while temperature, pH or ionic strength of the solutions were varied. Protein
      aggregation was also studied by determination of changes in fluorescence
      intensity, when the hydrophobicity probe, 8-anilinonaphthalenesulfonic acid (ANS)
      was added to solutions of the cuticular proteins. Only when the protein solutions
      had developed a measurable turbidity was an increase in ANS-fluorescence
      observed, indicating formation of tightly packed clusters of hydrophobic amino
      acid residues during aggregation. The temperature range for aggregation depends
      upon protein concentration: the higher the concentration the lower and more
      narrow is the temperature range within which aggregation occurs. The tendency for
      the individual cuticular proteins to aggregate is most pronounced near their
      isoelectric points, and most of the cuticular proteins have alkaline isoelectric
      points. The influence of salts on the tendency of the proteins to aggregate
      varies among the proteins and depends upon how close they are to their
      isoelectric point. A solution containing both protein TmLPCP-A1a and TmLPCP-E1a
      becomes more turbid and develops a more intense ANS-fluorescence when warmed from
      10 to 30 degrees C than corresponding to the sum of measurements performed on
      separate solutions of the two proteins, indicating that the two proteins interact
      during aggregation. The Tenebrio larval/pupal cuticular proteins are
      characterized by an abundance of hydrophobic amino acid residues, and especially
      their contents of alanine and proline are high. The behaviour of the cuticular
      proteins in solution resembles that of another hydrophobic protein, tropoelastin,
      and it seems reasonable to suggest that similar interactions govern the folding
      and aggregation of the peptide chains in the two types of proteins. The proline
      and alanine rich chain segments in the pharate cuticular proteins are suggested
      to form a series of beta-turns and to fold into a relatively open structure at
      low temperatures, giving water access to the hydrophobic residues and making the
      proteins water soluble. At increased temperatures the structure of the ordered
      water layer surrounding the hydrophobic groups breaks down, and the peptide
      chains tend to collapse into a more closed structure and to interact more tightly
      with hydrophobic regions in neighbouring molecules. In dilute solutions in the
      test tube this results in aggregation and precipitation of the proteins; in
      intact, pharate cuticle at ambient temperatures the proteins will preferably be
      in an aggregated, easily dissociated state. Accordingly, small changes in
      intercuticular pH and ionic strength can produce pronounced changes in the
      mechanical properties of unsclerotized solid cuticle by interference with protein
      interactions, in agreement with reports that some cuticles undergo plasticization
      during and/or immediately after ecdysis.

PMID- 12213245
TI  - Expression of allatostatin in the oviducts of the cockroach Diploptera punctata.
AB  - The cockroach allatostatins (Y/FXFGL/Ia ASTs) are a ubiquitous family of peptides
      in the invertebrates. They affect numerous physiological processes including the
      inhibition of juvenile hormone III (JH) biosynthesis, inhibition of muscle
      contraction, inhibition of ovarian ecdysteroid biosynthesis and inhibition of
      vitellogenin (Vg) release from the fat body. We have developed and optimized a
      sensitive and specific quantitative competitive reverse transcriptase polymerase
      chain reaction (QC-RT-PCR) method to quantify Diploptera punctata AST (Dippu-AST)
      expression. Using this technique we show that tissues of both lateral and common
      oviducts and the ovary express message for Dippu-AST. Moreover, the pattern of
      expression observed in the oviducts and ovary is strikingly similar with
      significant changes occurring during the reproductive cycle. Specifically,
      expression of AST is drastically reduced during the time of maximal vitellogenin
      (Vg) uptake, with higher levels measured prior to and following vitellogenesis.
      Furthermore, using immunocytochemistry, we have shown Dippu-AST-like
      immunoreactivity in the terminal abdominal ganglion, as well as in ventral nerve
      7, some branches of which innervate the common and lateral oviducts with other
      branches innervating the bursa copulatrix and brood sac of mated female D.
      punctata. The pattern of Dippu-AST expression and immunocytochemical staining
      suggests that ASTs function, in part, to regulate the cycle of vitellogenesis in
      mated female D. punctata.

PMID- 12213246
TI  - Toward a description of the sialome of the adult female mosquito Aedes aegypti.
AB  - To describe the set of mRNA and protein expressed in the salivary glands
      (sialome) of Aedes aegypti mosquitoes, we randomly sequenced a full-length cDNA
      library of this insect and performed Edman degradation of PVDF-transferred
      protein bands from salivary homogenates. We found 238 cDNA clusters which
      contained those coding for 10 of the 11 proteins found by aminoterminal
      degradation. All six previously described salivary proteins were found in this
      library. Full-length sequences of 32 novel cDNA sequences are reported, one of
      which is the product of a transposable element. Among the 31 novel protein
      sequences are 4 additional members of the D7 protein family; 4 novel members of
      the antigen 5 family (a protein family not reported in Aedes); a novel serpin; a
      novel member of the 30-kDa allergen of Ae. Aegypti; a secreted calreticulin; 2
      proteins similar to mammalian angiopoietins; adenosine deaminase; purine
      hydrolase; lysozyme; a C-type lectin; 3 serine proteases, including one with high
      similarity to Bombyx prophenoloxidase activating enzyme; 2 proteins related to
      invertebrate immunity; and several sequences that have no significant matches to
      known proteins. The possible role of these proteins in blood and sugar feeding by
      the mosquito is discussed.

PMID- 12213247
TI  - Characterisation of aminopeptidase activity in scab mites (Psoroptes spp.).
AB  - Soluble and membrane-bound aminopeptidase activities were demonstrated in
      extracts of P. cuniculi (Delafond). Leucine aminopeptidase (LAP) activity in the
      soluble fraction of P. cuniculi extracts displayed substrate preference for amino
      acid derivatives with terminal leucine and methionine over those with acidic,
      basic or heterocyclic groups. P. cuniculi LAP was inhibited by leucinethiol
      (IC(50) = 1.4 +/- 0.4 nM), bestatin (IC(50) = 3.9 +/- 1.7 microM), Arphamenine A
      (IC(50) = 0.37 +/- 0.03 mM) the chelating agent 1,10-phenanthroline (IC(50) = 2.3
      +/- 0.5 mM), Zn(2+), Cu(2+) Ni(2+), and Co(2+), and activated by Mn(2+) and
      Mg(2+). The LAP activity was visualised as a single major band after
      electrophoresis on native gels and eluted from a size exclusion column as a
      single major peak representing a molecular mass range of 85-116 kDa. Degenerate
      oligonucleotide primers were used to amplify short fragments of genomic DNA
      containing nucleotide sequence coding for the cation-binding motifs of the co
      catalytic Zn(2+) binding domains of dizinc leucine aminopeptidases in both P.
      cuniculi and P.ovis (Hering). The major soluble aminopeptidase from these mites
      therefore displays most of the characteristics associated with typical cytosolic
      leucine aminopeptidases belonging to the M17 family of metalloproteinases.

PMID- 12213248
TI  - Control of phospholipase A(2) activity in cockroach (Periplaneta americana) fat
      body trophocytes by hypertrehalosemic hormone: the role of calcium.
AB  - Recently, synthetic HTH-I and HTH-II have been shown to increase the formation of
      free fatty acids in cockroach (Periplaneta americana) fat body. In this study we
      show that HTH-II increases PLA(2) activity in dispersed trophocytes, thus
      implying that phospholipid is a potential source of the fatty acids. The increase
      in HTH-induced PLA(2) activity is triggered by an increase in [Ca(2+)](i) but
      extracellular Ca(2+) is also required for a maximal Ca(2+) signal: an effect that
      can be blocked by the introduction of BAPTA into the trophocytes. Treating
      trophocytes with ryanodine blocks the increase in PLA(2) activity that follows
      treatment of the cells with HTH-II. This indicates that the Ca(2+) release
      channels are distinct from those that respond to inositol trisphosphate.
      Thapsigargin, which releases Ca(2+) to the cytosol from an intracellular store,
      increases PLA(2) activity. The data show that the enzyme is translocated from the
      cytosol to the plasma membrane.

PMID- 12213249
TI  - Properties of the V-type ATPase from the excretory system of the usherhopper,
      Poekilocerus bufonius.
AB  - The bafilomycin A(1) and N-ethylmaleimide (NEM)-sensitive (V-type) ATPase was
      partially purified from the apical membrane-rich fractions of excretory system
      (Malpighian tubules and hind gut) of P. bufonius. Enzymatic activity was
      inhibited by bafilomycin A(1) (IC(50) = 1.3 nM) and NEM (IC(50) = 10.1 microM).
      The V-type ATPase activity is confined to the apical membrane fraction, while the
      activity of Na(+)/K(+) -ATPase forms the major part of the basal membrane
      fraction. The optimal pH required for maximal activity of V-type ATPase was pH
      7.5. The effect of 30 mM of various salts on ATPase activity was investigated.
      NaCl and KCl caused increases of 175% and 184%, respectively. Other chloride
      salts also caused an increase in activity in the following ascending order: RbCl,
      LiCI, choline Cl, NaCI, KCl and tris-HCl. The activity of V-type ATPase was
      stimulated by a variety of different anions and cations, and HCO(3)(-) was found
      to be the most potent cationic activator of ATPase activity. The present results
      show that the properties of V-type ATPase of P. bufonius are similar to those
      reported for other insect tissues.

PMID- 12213250
TI  - Characterization of cholesterol transport from midgut to fat body in Manduca
      sexta larvae.
AB  - Using in vitro methods, we investigated the transfer of cholesterol from larval
      Manduca sexta midgut to the hemolymph lipoprotein, lipophorin, and the transfer
      of cholesterol from lipophorin to larval fat body. In the midgut, transfer of
      free cholesterol shows saturation kinetics, but the apparent Km is higher than
      the measured Kd for the midgut lipophorin-receptor complex. In addition, the
      transfer is unaffected by suramin, which binds to the receptor and inhibits
      lipophorin binding, and by antibodies to the lipid transfer particle, which is
      required for export of diacylglycerol from the midgut to lipophorin. In the fat
      body, transfer of free cholesterol also shows saturation kinetics, and the
      apparent Km is higher than the measured Kd for the fat body lipophorin-receptor
      complex. Suramin and anti-lipid transfer particle antibodies exert only a small
      (20%) inhibitory effect. In both tissues it seems that the most likely mode of
      cholesterol transfer is via aqueous diffusion, which is also an important
      mechanism in vertebrate cells. Based on these results, we propose that
      cholesterol homeostasis in larval M. sexta is maintained by a mass action
      mechanism in which cholesterol is freely transferred between lipophorin and
      tissues depending on the needs of the tissues. This simple mechanism is ideally
      suited to insects, which can neither make cholesterol nor internalize lipophorin,
      the two mechanisms that vertebrate cells use to control their cholesterol
      content.

PMID- 12213251
TI  - Drosophila melanogaster dihydroorotate dehydrogenase: the N-terminus is important
      for biological function in vivo but not for catalytic properties in vitro.
AB  - Dihydroorotate dehydrogenase (DHODH, EC 1.3.99.11), the fourth enzyme of
      pyrimidine de novo synthesis, is an integral flavoprotein of the inner
      mitchondrial membrane and is functionally connected to the respiratory chain.
      Here, experiments have been directed toward determining the roles of the N
      terminal sequence motifs both in enzymatic properties of insect DHODH produced in
      vitro and the in vivo function of the protein. Full-length and three N-terminal
      truncated derivatives of the Drosophila melanogaster enzyme were expressed in
      Escherichia coli and purified. For identification on Western blots of recombinant
      DHODH as well as the native enzyme from flies polyclonal anti-DHODH
      immunoglobulins were generated and affinity-purified. The enzymatic
      characteristics of the four versions of DHODH were very similar, indicating that
      the N-terminus of the enzyme does not influence its catalytic function or its
      susceptibility to prominent DHODH inhibitors: A77-1726, brequinar, dichloroallyl
      lawsone and redoxal. Whereas the efficacy of A77-1726 and dichloroallyl-lawsone
      were similar with Drosophila and human DHODH, that of brequinar and redoxal
      differed significantly. The differences in responses of insect DHODH and the
      enzyme from other species may allow the design of new agents that will
      selectively control insect growth, due to pyrimidine nucleotide limitation. In
      vivo expression of the full-length and N-truncated DHODHs from engineered
      transgenes revealed that the truncated proteins could not support normal de novo
      pyrimidine biosynthesis during development of the fly (i.e., failure to
      complement dhod-null mutations), apparently due to instability of the truncated
      proteins. It is concluded that the proper intracellular localization, directed by
      the N-terminal targeting and transmembrane motifs, is required for stability and
      subsequent proper biological function in vivo.

PMID- 12213252
TI  - Characterization of four Toll related genes during development and immune
      responses in Anopheles gambiae.
AB  - Toll-like receptors (TLRs) are a group of evolutionary conserved proteins with
      diverse biological functions. In Drosophila melanogaster, Toll protein plays an
      important role in pattern formation in embryogenesis and in antimicrobial
      immunity in larvae and adults. In insects, Toll and two other related proteins,
      Tehao and 18-wheeler have been shown to participate in the activation of the
      innate immune responses to fungal and bacterial pathogens. In this paper we
      report the cloning and characterization of four TLR gene from malaria vector
      mosquito Anopheles gambiae, AgToll, AgToll6, AgTrex, and AgToll9, orthologues of
      DmToll, DmToll6, DmTollo (Toll8) and DmToll9 (CG5528) in Drosophila melanogaster.
      The expression profiles of these genes during development, in different adult
      tissues and after immune challenge were examined. As expected for the orthologue
      of Drosophila Toll, AgToll was found to be expressed highly in the ovary and may
      play a role in pattern formation during embryogenesis. AgToll9, surprisingly, was
      found to be highly expressed in the adult gut. The potential roles of these genes
      in development and immunity were discussed.

PMID- 12213253
TI  - Purification and characterization of a carboxylesterase involved in malathion
      specific resistance from Tribolium castaneum (Coleoptera: Tenebrionidae).
AB  - Specific resistance to malathion in a strain of Tribolium castaneum is due to a
      44-fold increase in malathion carboxylesterase (MCE) activity relative to a
      susceptible strain, whereas non-specific esterase levels are slightly lower.
      Unlike the overproduced esterase of some mosquito and aphid species, MCE in
      Tribolium castaneum accounts for only a small fraction (0.033-0.045%) of the
      total extractable protein respectively in resistant and susceptible strains. The
      enzyme was purified to apparent homogeneity from these two strains and has a
      similar molecular weight of 62,000. However, preparative isoelectricfocusing
      indicated that resistant insects possess one MCE with pI of 7.3, while
      susceptible insects possess a MCE with a pI of 6.6. Purified MCE from both
      populations had different K(m) and V(m) values for hydrolysis of malathion as
      well as for alpha-naphthyl acetate. The kinetic analysis suggests that MCE of
      resistant insects hydrolyses malathion faster than the purified carboxylesterase
      from susceptible beetles and that this enzyme has greater affinity for malathion
      than for naphthyl esters. Malathion-specific resistance is due to the presence of
      a qualitatively different esterase in the resistant strain.

PMID- 12213254
TI  - An AMPA receptor potentiator modulates hippocampal expression of BDNF: an in vivo
      study.
AB  - AMPA receptor activation has been demonstrated to increase the neuronal
      expression of brain derived neurotrophic factor (BDNF). In the present study, we
      investigated the effect of a novel AMPA receptor potentiator (LY404187) and its
      active isomer (LY451646) on the expression of BDNF protein and mRNA, as well as
      TrkB mRNA in rat hippocampus. LY404187 administered for 7 days (1 mg/kg)
      significantly increased the number of BDNF immunopositive cells in the dentate
      gyrus, but not other hippocampal subfields. Chronic treatment (7 days) with
      LY451646 (0.5 mg/kg, comparable to 1 mg/kg of LY404187) increased the level of
      both BDNF and TrkB mRNA expression in the dentate gyrus, CA3 and CA4 of the
      hippocampus. However, chronic treatment with lower doses of LY451646 (0.125 and
      0.25 mg/kg) decreased the level of BDNF and TrkB mRNA in hippocampus, whilst the
      highest used dose of LY451646 (1 mg/kg) had no effect on BDNF and TrkB mRNA in
      hippocampus. In contrast, acute treatment with LY451646 produced an increase in
      BDNF mRNA levels at doses of 0.125 and 0.25 mg/kg in the hippocampus (CA4, CA3
      and dentate gyrus, but not in CA1). LY451646 at 0.5 mg/kg had no effect, but at
      1.0 mg/kg decreased the level of BDNF mRNA in hippocampus. Acute treatment with
      LY451646 did not affect the TrkB receptor mRNA levels in hippocampus. Our results
      demonstrate that biarylpropylsulfonamide AMPA receptor potentiators are capable
      of modulating the expression of BDNF and TrkB mRNA in a dose- and time-dependent
      manner. The increase in both BDNF protein and mRNA expression in the dentate
      gyrus but not in CA1 indicates a specific role of AMPA receptors in the
      regulation of BDNF expression in this hippocampal subfield. The regulation of
      BDNF expression by biarylpropylsulfonamids such as LY451646 may have important
      therapeutical implications for this class of molecule in the treatment of
      depression and other CNS disorders.

PMID- 12213256
TI  - Effects of kainic acid on rat body temperature: unmasking by dizocilpine.
AB  - The effects of intraperitoneal (i.p.) administration of kainic acid (KA) and
      dizocilpine, alone or in combination, on body temperature of freely moving rats
      were examined. Injection of saline or dizocilpine (3.0 or 5.0 mg/kg) was followed
      after an hour by injection of saline or KA (10 mg/kg) and the body temperature
      was measured at different time points during the first 5 h. KA alone produced an
      initial short-lasting hypothermia followed by a longer-lasting hyperthermic
      effect. Administration of dizocilpine alone produced an early increase in core
      temperature. Pretreatment of KA-injected rats with dizocilpine potentiated the KA
      induced hypothermic effect at 30 min and dose-dependently reduced the temperature
      measured at 1 h after KA-injection without influencing the ensuing
      hyperthermia.These data suggest that the KA-induced changes in body temperature
      do not necessarily involve the activation of NMDA-receptors as opposed to KA
      induced behavioural changes that are blocked by dizocilpine in a dose-dependent
      manner. It is unlikely, therefore, that the KA-induced hyperthermia is a result
      of the KA-induced seizure motor activity. Furthermore, our findings indicate that
      KA-induced changes in core temperature may be used as a criterion of drug
      responsiveness when the behavioural changes are blocked, e.g. with dizocilpine.

PMID- 12213255
TI  - Selective enhancement of AMPA receptor-mediated function in hippocampal CA1
      neurons from chronic benzodiazepine-treated rats.
AB  - Two days following one-week administration of the benzodiazepine, flurazepam
      (FZP), rats exhibit anticonvulsant tolerance in vivo, while reduced GABA(A)
      receptor-mediated inhibition and enhanced EPSP amplitude are present in CA1
      pyramidal neurons in vitro. AMPA receptor (AMPAR)-mediated synaptic transmission
      in FZP-treated rats was examined using electrophysiological techniques in in
      vitro hippocampal slices. In CA1 pyramidal neurons from FZP-treated rats, the
      miniature excitatory postsynaptic current (mEPSC) amplitude was significantly
      increased (33%) without change in frequency, rise time or decay time. Moreover,
      mEPSC amplitude was not elevated in dentate granule neurons following 1-week FZP
      treatment or in CA1 pyramidal neurons following acute desalkyl-FZP treatment.
      Regulation of AMPAR number was assessed by quantitative autoradiography with the
      AMPAR antagonist, [(3)H]Ro48-8587. Specific binding was significantly increased
      in stratum pyramidale of hippocampal areas CA1 and CA2 and in proximal dendritic
      fields of CA1 pyramidal neurons. Regulation of AMPAR subunit proteins was
      examined using immunological techniques. Neither abundance nor distribution of
      GluR1-3 subunit proteins was different in the CA1 region following FZP treatment.
      These findings suggest that enhanced AMPAR currents, mediated at least in part by
      increased AMPAR number, may contribute to BZ anticonvulsant tolerance.
      Furthermore, these studies suggest an interaction between GABAergic and
      glutamatergic systems in the CA1 region which may provide novel therapeutic
      strategies for restoring BZ effectiveness.

PMID- 12213257
TI  - Aging alters in a region-specific manner serotonin transporter sites and 5-HT(1A)
      receptor-G protein interactions in hamster brain.
AB  - Key proteins regulating serotonergic activity, specifically the serotonin
      transporter and 5-HT(1A) receptor, were examined in the midbrain raphe nuclei of
      young (3-4 months) and old (17-19 months) hamsters (N=7-10/group). An age-related
      decrease in the maximal density of serotonin transporter sites labelled with
      [(3)H]paroxetine (fmol/mg protein, Old: 396+/-13; Young: 487+/-27) was observed
      in the dorsal raphe nucleus (DRN) but not the median raphe nucleus (MRN), without
      affecting the affinity of [(3)H]paroxetine. In the DRN and MRN, the stimulation
      of [(35)S]GTP gamma S binding by the 5-HT(1A) receptor agonist 8-OH-DPAT, or the
      number of 5-HT(1A) receptor sites labeled with [(3)H] MPPF, was not different in
      old versus young animals. Thus in the DRN, aging decreased serotonin transporter
      sites without changing 5-HT(1A) receptor activation of G proteins or 5-HT(1A)
      receptor density. In the CA(1) region of hippocampus, 8-OH-DPAT-stimulated
      [(35)S]GTP gamma S binding was increased in the older animals (% above basal,
      Old: 141+/-21; Young: 81+/-17) without changing specific [(3)H] MPPF binding
      sites, suggesting that the capacity of 5-HT(1A) receptors to activate G proteins
      is enhanced. Aging also appears to enhance this capacity in the dentate gyrus,
      because this region exhibited a constant level of 8-OH-DPAT-stimulated [(35)S]GTP
      gamma S binding in spite of an age-related decrease in the number of [(3)H] MPPF
      binding sites (fmol/mg protein, Old: 203+/-21; Young: 429+/-51).

PMID- 12213258
TI  - Treatment of cycling female rats with fluoxetine induces desensitization of
      hypothalamic 5-HT(1A) receptors with no change in 5-HT(2A) receptors.
AB  - Although women constitute the majority of patients who receive treatment with
      selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, most animal
      studies of SSRIs are conducted on males. The present study investigated whether
      long-term treatment of cycling female rats with fluoxetine alters their estrous
      cycle and the sensitivity of hypothalamic serotonin (5-HT) 5-HT(1A) and 5-HT(2A)
      receptor systems. Adult female rats received daily injections of fluoxetine (10
      mg/kg, i.p.) for three consecutive estrous cycles (15.2+/-0.2 days) with the
      first injection beginning on metestrus (when circulating estrogen levels are low
      and stable). Fluoxetine did not alter basal plasma estradiol levels at metestrus,
      nor did it alter the pattern of estrous cyclicity. Rats treated with fluoxetine
      showed a loss in body weight. On the morning of metestrus of the fourth cycle (18
      h after the last fluoxetine injection), the rats were injected with a sub-maximal
      dose of the 5-HT(1A) agonist (+/-)-8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT,
      50 MICRO/kg, s.c.) or a maximal dose of the 5-HT(2A) agonist [(+/-)-1-(2,5
      dimethoxy-4-iodophenyl)-2-aminopropane HCl] (DOI). Plasma levels of oxytocin,
      ACTH and corticosterone were measured as peripheral indicators of hypothalamic 5
      HT(1A) and 5-HT(2A) receptor sensitivity. Injecting 8-OH-DPAT to saline
      pretreated rats produced a significant increase in plasma oxytocin (299%), ACTH
      (1456%) and corticosterone (170%) levels but not in plasma prolactin or renin
      concentrations. Greater increases in plasma levels of these hormones were
      observed after injecting DOI. Fluoxetine treatment completely blocked the
      oxytocin, ACTH and corticosterone responses to 8-OH-DPAT, but did not inhibit the
      effect of DOI on any hormone, thus confirming that fluoxetine treatment did not
      produce a deficit in the functioning of corticotropin releasing hormone or
      oxytocin containing neurons. These results indicate that in cycling female rats,
      fluoxetine treatment desensitizes hypothalamic post-synaptic 5-HT(1A) receptor
      signaling. Understanding the pharmacological effects of fluoxetine in females may
      lead to more effective treatment of women with mood disorders.

PMID- 12213259
TI  - Proconvulsant-induced seizures in alpha(4) nicotinic acetylcholine receptor
      subunit knockout mice.
AB  - The genetic basis of a number of epilepsy syndromes has been identified but the
      precise mechanism whereby these mutations produce seizures is unknown. Three
      mutations of the alpha(4) subunit of the neuronal nicotinic acetylcholine
      receptor (nAChR) have been identified in autosomal dominant nocturnal frontal
      lobe epilepsy. In vitro studies of two mutations suggest an alteration of
      receptor function resulting in decreased ion channel current flow. We
      investigated the response of alpha(4) nAChR subunit knockout mice to the gamma
      aminobutyric acid (GABA) receptor antagonists; pentylenetetrazole (PTZ) and
      bicuculline (BIC), the glutamate receptor agonist kainic acid (KA), the glycine
      receptor antagonist strychnine and the K(+) channel blocker 4-aminopyridine (4
      AP). Mutant (Mt) mice had a greater sensitivity to PTZ and BIC, with an increase
      in major motor seizures and seizure-related deaths. Furthermore, Mt mice were
      more sensitive to KA and strychnine, but the effects were much smaller compared
      to those seen with the GABA receptor antagonists. Paradoxically, Mt mice appeared
      to be relatively protected from 4-AP-induced major motor seizures and death. The
      results show that a functional deletion of the alpha(4) nAChR subunit in vivo is
      associated with a major increase in sensitivity to GABA receptor blockers.

PMID- 12213260
TI  - Identification of threonine 422 in transmembrane domain alpha M4 of the nicotinic
      acetylcholine receptor as a possible site of interaction with hydrocortisone.
AB  - The modulatory effects exerted by the glucocorticoid hydrocortisone (HC) on the
      nicotinic acetylcholine receptor (AChR) were studied in mutants of the alpha
      subunit M4 transmembrane region. Based on the photoaffinity labeling of alpha M4
      412 with the steroid promegestone this position was mutated to different residues
      to explore the properties of side-chain volume, hydrophobicity, and charge on
      AChR-steroid interactions. All mutants showed channel kinetics indistinguishable
      from those of the wild-type AChR, both in the absence and presence of HC (200 and
      400 microM), in single-channel recordings at different acetylcholine (ACh)
      concentrations. An alanine-substituted quadruple mutant of four putative lipid
      exposed residues in alpha M4 (L411, M415, C418 and T422) exhibited less
      inhibition by HC than that observed in wild-type AChR. When we dissected the
      quadruple mutant into four individual alanine-substituted receptors, we found
      that the T422 mutant AChR behaved like the quadruple mutant, whereas the other
      three were indistinguishable from the wild-type. We conclude that T422, a residue
      close to the extracellular-facing membrane hemilayer in alpha M4, has direct
      bearing on the changes in HC sensitivity and propose its involvement in the
      steroid-AChR interaction site.

PMID- 12213261
TI  - 5-Isothiocyanato-2-benzofuranyl-2-imidazoline (BU99006) an irreversible
      imidazoline(2) binding site ligand: in vitro and in vivo characterisation in rat
      brain.
AB  - 5-Isothiocyanato-2-benzofuranyl-2-imidazoline (BU99006) is an irreversible ligand
      based on the highly selective I(2) binding site ligand 2BFI. In competition
      binding assays it has been shown to have high affinity and selectivity for the
      I(2) binding site and to irreversibly inhibit the binding of [(3)H]2BFI. In this
      present study we have sought to confirm and expand on these findings both in
      vitro and in vivo. In vitro pre-incubation of rat whole brain membranes with
      BU99006 (10 microM) was shown to reduce the specific binding of [(3)H]2BFI to 10%
      of the control values, an effect not seen using 2BFI or BU224. Pre-treatment of
      rat whole brain membranes by BU99006, or by the alpha(2)-adrenoceptor antagonists
      RX821002 or rauwolscine had no effect on the specific binding of [(3)H]RX821002.
      In vivo pre-treatment of rats with BU99006 (15 mg x kg(-1), i.v.) caused a
      substantial loss of [(3)H]2BFI specific binding in subsequent in vitro saturation
      analysis and autoradiography; this loss was shown to be dose dependent. These
      data indicate that BU99006 is selectively and irreversibly affecting I(2) binding
      sites both in vitro and in vivo and that it represents an invaluable tool in the
      further understanding of the I(2) binding site.

PMID- 12213262
TI  - Rhythmic activity from transverse brainstem slice of neonatal rat is modulated by
      nitric oxide.
AB  - We investigated the role of nitric oxide (NO) in the modulation of respiratory
      like activity recorded from hypoglossal rootlets in brainstem slices of neonatal
      rats (P0-P8). Sodium nitroprusside (SNP), S-Nitroso-N-acetyl-D,L-penicillamine
      (SNAP) and diethylamine-NO (DEA-NO), three NO-donors, reversibly increased
      hypoglossal burst amplitude with inconsistent effects on burst frequency. Similar
      effects were also obtained with the endogenous substrate of nitric oxide synthase
      (NOS), L-arginine, whereas the inactive enantiomer D-arginine had no effect. The
      NO-trap agent methylene blue significantly depressed both the amplitude and
      frequency of hypoglossal activity while hemoglobin depressed only the amplitude.
      Furthermore, the addition of NO-trap agents significantly attenuated the
      excitatory response to SNP. Inhibiting NOS with either N(omega)-Nitro-L-Arginine
      (L-NNA) or 7-Nitroindazole (7-NI), decreased the amplitude of hypoglossal
      activity with no effects on frequency. Histochemical analysis of NADPH-diaphorase
      activity, a marker for NOS, was performed on slices not treated pharmacologically
      and in brainstem sections of newborn rats, perfused in situ. Comparison between
      in vitro and in vivo conditions indicated that NOS activity was maintained in
      slice preparations. Neurons in the ambiguus and hypoglossal nuclei (dorsal
      division) exhibited a granular staining, suggesting the presence of NADPHd
      positive terminals. Neurons with cytoplasmic staining were identified in regions
      connected to the hypoglossal nucleus (nucleus tractus solitarius, paramedian and
      gigantocellular reticular nuclei). These neurons might be involved in nitrergic
      control of hypoglossal activity. Both pharmacological and histochemical data
      suggest that endogenous NO may reinforce the output activity of the medullary
      respiratory network.

PMID- 12213263
TI  - Lu 28-179 labels a sigma(2)-site in rat and human brain.
AB  - 1'-[4-[1-(4-Fluorophenyl)-1H-indol-3-yl]-1-butyl]spiro[isobenzofuran-1(3H),4'
      piperidine] (Lu 28-179) or Siramesine is a sigma-ligand with high specificity for
      sigma(2)-sites, has been tritiated to directly label these sites in brain.
      [(3)H]Lu 28-179 bound in a saturable manner to homogenates prepared from rat
      brain or human cortices with high affinity (K(d)=2.2 and 1.1 nM, respectively)
      and moderate capacity (B(max)=50+/-12 and 26+/-3 fmol mg tissue(-1),
      respectively). The rank order of affinity for [(3)H]Lu 28-179 binding to
      homogenates from human and rat brain was: Lu 28-179>ifenprodil=haloperidol>1,3
      di(2-tolyl)-guanidine (DTG)>(-)pentazocinez.Gt;(+)pentazocine. Using in vitro
      receptor autoradiography to rat brain sections [(3)H]Lu 28-179 binding was shown
      to be most predominant in the cerebral cortex, piriform cortex, hippocampal
      formation (CA1-CA3 and dentate gyrus), superior colliculus, molecular layer of
      the cerebellar cortex and locus coeruleus. Overall, these data are consistent
      with [(3)H]Lu 28-179 labelling a sigma(2)-like binding site.

PMID- 12213264
TI  - Repetitive transcranial magnetic stimulation increases the release of dopamine in
      the mesolimbic and mesostriatal system.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is suggested to be a
      potentially useful treatment in major depression. In order to optimize rTMS for
      therapeutic use, it is necessary to understand the neurobiological mechanisms
      involved, particularly the nature of the neurochemical changes induced. Using
      intracerebral microdialysis in urethane-anesthetized and conscious adult male
      Wistar rats, we monitored the effects of acute rTMS (20 Hz) on the
      intrahippocampal, intraaccumbal and intrastriatal release patterns of dopamine
      and its metabolites (homovanillic acid, 3,4-dihydroxyphenylacetic acid). The
      stimulation parameters were adjusted according to the results of accurate MRI
      based computer-assisted reconstructions of the current density distributions
      induced by rTMS in the rat brain, ensuring stimulation of frontal brain regions.
      In the dorsal hippocampus, the shell of the nucleus accumbens and the dorsal
      striatum the extracellular concentration of dopamine was significantly elevated
      in response to rTMS. Taken together, these data provide the first in vivo
      evidence that acute rTMS of frontal brain regions has a modulatory effect on both
      the mesolimbic and the mesostriatal dopaminergic systems. This increase in
      dopaminergic neurotransmission may contribute to the beneficial effects of rTMS
      in the treatment of affective disorders and Parkinson's disease.

PMID- 12213265
TI  - Comparison of the effects of modafinil and sleep deprivation on sleep and
      cortical EEG spectra in mice.
AB  - Modafinil is a wakefulness-promoting substance whose profile differs from that of
      the classical psychostimulants. It is still unknown whether waking induced by
      modafinil and wakefulness induced by sleep deprivation differ in terms of their
      effect on subsequent sleep. To investigate this problem sleep was recorded in two
      groups of OF1 mice. One group received modafinil (200 mg/kg, i.p.) at light onset
      which induced a period of wakefulness of approx. 5 h, while animals of the
      subsequent control group were injected with vehicle and kept awake for an
      equivalent duration. The effect of the two treatments on sleep was similar. REM
      sleep was initially reduced and slow-wave activity (SWA; EEG power in the 0.75
      4.0 Hz range) in nonREM sleep was enhanced for several hours. The SWA increase
      was more prominent over the frontal cortex than over the occipital cortex after
      both treatments. A minor difference was seen at the occipital site where the
      initial rise of power in the low-frequency range was larger after vehicle
      combined with enforced waking than after modafinil. The study shows that the
      homeostatic sleep response following the modafinil-induced wakefulness
      corresponds largely to the response following a non-pharmacologically induced
      extended waking episode.

PMID- 12213266
TI  - Metabotropic glutamate 1 (mGlu1) receptor antagonists enhance GABAergic
      neurotransmission: a mechanism for the attenuation of post-ischemic injury and
      epileptiform activity?
AB  - Selective antagonists of mGlu1 metabotropic glutamate receptors attenuate
      neuronal death in models of cerebral ischemia. Because GABAergic mechanisms have
      recently been proposed to contribute to these neuroprotective effects, we
      examined the effects of selective mGlu1 antagonists characterized in our
      laboratory on GABAergic transmission in three different models of neuropathology.
      In rat organotypic hippocampal slices exposed to oxygen-glucose deprivation, the
      mGlu1 antagonists AIDA, CBPG and 3-MATIDA reduced CA1 pyramidal cell loss when
      added to the medium during the insult and the subsequent recovery period. This
      effect was mimicked by the GABA(A) and GABA(B) agonists muscimol and baclofen and
      partially prevented by the antagonists bicuculline and CGP 55845. In gerbils
      subjected to global ischemia, protection of CA1 pyramidal cells by transdialytic
      perfusion of AIDA and CBPG was associated with a significant increase in the
      basal and ischemic output of GABA and minor changes in the output of glutamate.
      In a mouse cortical wedge model, both muscimol and 3-MATIDA reduced the frequency
      of spontaneous bursts induced by 4-aminopyridine and this reduction was prevented
      by co-perfusion with bicuculline. Taken together, our results suggest that the
      release of GABA, and the subsequent activation of GABA receptors, may contribute
      to the attenuation of post-ischemic neuronal damage and epileptiform activity
      induced by mGlu1 receptor antagonists.

PMID- 12213267
TI  - Complex interactions between mGluR1 and mGluR5 shape neuronal network activity in
      the rat hippocampus.
AB  - Group I metabotropic glutamate receptors (mGluRs) cause increased neuronal
      excitability that can lead to epileptogenesis and neurodegeneration. Here we have
      examined how individual members of this subgroup of mGluRs affect synchronised
      hippocampal synaptic activity under normal and disinhibited conditions similar to
      those that occur during certain epileptic states. We demonstrate that activation
      of both mGluR1 and mGluR5 are important in increasing neuronal synaptic
      excitability by increasing synchrony between cells and driving correlated network
      activity in circuits that contain, or are devoid of, GABA(A) receptor-mediated
      synaptic inputs. The precise patterning of activity that occurs is complex and
      depends upon: (1) the existing pattern of ongoing network activity prior to mGluR
      activation; and (2) the relative extent of activation of each mGluR subtype.
      However, mGluR5 appears to be the principal mGluR subtype that initiates bursting
      activity irrespective of the inhibitory synaptic tone within the neuronal
      network.

PMID- 12213268
TI  - Group I mGluRs modulate the pattern of non-synaptic epileptiform activity in the
      hippocampus.
AB  - The hippocampus is well known for its susceptibility to epileptic seizures, in
      part because of its neuronal architecture that facilitates synchronization.
      Although synaptic networks are important for the genesis and spread of
      epileptiform activity, synchronization of neuronal activity can occur when action
      potential-dependent chemical synaptic transmission is absent. In particular, it
      is possible to induce epileptiform activity by perfusing hippocampal slices with
      a low-Ca(2+)/high-K(+) mediums. Using extracellular recording in area CA1 we have
      characterized the effects of metabotropic glutamate receptor (mGluR) activation
      on this non-synaptic bursting activity. Under control conditions, bursting
      occurred at intervals of 14-86 s with each burst comprising a long (up to 44 s)
      negative-going field potential of 2 to 13 mV superimposed upon which was
      sustained firing of population spikes. Activation of group I mGluRs by (S)-3,5
      dihydroxyphenylglycine (DHPG) (25 microM) caused a dramatic increase in burst
      frequency (up to five-fold), which was accompanied by a decrease in the duration
      and amplitude of bursts. The selective mGluR(1) antagonist 2-methyl-4
      carboxyphenylglycine (LY367385) and the selective mGluR(5) antagonist 2-methyl-6
      (phenylethynyl)pyridine (MPEP) both restricted the increase in burst frequency
      induced by DHPG. However, only LY367385 inhibited the decrease in burst duration
      and amplitude. Combined application of both antagonists prevented all DHPG
      induced changes in bursting activity. These data provide evidence for a role of
      both mGluR(1) and mGluR(5) subtypes in changing the frequency of non-synaptic
      bursting, with mGluR(1) alone causing alterations in burst duration and
      amplitude. These effects are likely to contribute to the group I mGluR-induced
      changes in synaptic epileptic activity that are already well documented.

PMID- 12213269
TI  - Haloperidol-induced alteration in the physiological actions of group I mGlus in
      the subthalamic nucleus and the substantia nigra pars reticulata.
AB  - Excitatory glutamatergic inputs to the subthalamic nucleus (STN), and subthalamic
      afferents to the substantia nigra pars reticulata (SNr) are believed to play a
      key role in the pathophysiology of Parkinson's disease (PD). Previously, we have
      shown that activation of the group I mGlus in the STN and SNr induces a direct
      depolarization of the neurons in these nuclei. Surprisingly, although both group
      I mGlus were present in the STN and SNr, mGlu5 alone mediated the DHPG-induced
      depolarization of the STN, and mGlu1 alone mediated the DHPG-induced
      depolarization of the SNr. We now report that both mGlu1 and mGlu5 are
      coexpressed in the same cells in both of these brain regions, and that both
      receptors play a role in mediating the DHPG-induced increase in intracellular
      calcium. Furthermore, we demonstrate that the induction of an acute PD-like state
      using a 16 h haloperidol treatment produces an alteration in the coupling of the
      group I receptors, such that post-haloperidol, DHPG-induced depolarizations are
      mediated by both mGlu1 and mGlu5 in the STN and SNr. Therefore, the pharmacology
      of the group I mGlu-mediated depolarization depends on the state of the system,
      and alterations in receptor coupling may be evident in pathological states such
      as PD.

PMID- 12213270
TI  - Tyrosine phosphorylation of the metabotropic glutamate receptor mGluR5 in
      striatal neurons.
AB  - Protein phosphorylation, controlled by the coordinated actions of phosphatases
      and kinases, is an important regulatory mechanism in synaptic transmission and
      other neurophysiological processes. Ionotropic glutamate receptors are known
      targets of phosphorylation on serine, threonine and tyrosine residues, with
      functional consequences for cell excitability, plasticity and toxicity. While
      phosphorylation of metabotropic glutamate receptors (mGluRs) also impacts
      critical cellular processes, there has been no evidence for direct tyrosine
      phosphorylation of mGluRs. In the present study, anti-phosphotyrosine and
      specific mGluR antibodies were used to detect tyrosine-phosphorylated mGluRs in
      rat brain. In particular, we found that mGluR5 is an abundant phosphotyrosine
      protein in vivo as well as in primary striatal neurons and tissue slices in
      vitro. The protein phosphatase inhibitor pervanadate robustly increased the
      amount of tyrosine-phosphorylated mGluR5, suggesting the receptor is subject to
      an endogenous, active cycle of phosphorylation and dephosphorylation.
      Furthermore, NMDA treatment also increased the amount of tyrosine-phosphorylated
      mGluR5, suggesting these endogenous phosphorylation regulatory mechanisms can be
      used to mediate crosstalk between synaptic glutamate receptors. While mGluR5
      stimulated phosphoinositide hydrolysis appears to be unaltered by pervanadate
      treatment, tyrosine phosphorylation of mGluR5 may be important in trafficking,
      anchoring, or signaling of the receptor through G protein-independent pathways.

PMID- 12213271
TI  - Tyrosine dephosphorylation underlies DHPG-induced LTD.
AB  - A form of long-term depression (LTD) of synaptic transmission can be induced by
      bath application of the group I metabotropic glutamate (mGlu) receptor agonist
      (RS)-3,5-dihydroxyphenylglycine (DHPG). The mechanisms responsible for the
      induction and expression of DHPG-induced LTD in the CA1 region of the hippocampus
      are currently the subject of intense investigation. Here we show that two protein
      tyrosine kinase (PTK) inhibitors (10 microM lavendustin A or 30 microM genistein)
      have little effect on DHPG-induced LTD. In contrast two protein tyrosine
      phosphatase (PTP) inhibitors (1 mM orthovanadate or 15 microM phenyl-arsine
      oxide) significantly inhibited DHPG-induced LTD. These data suggest that DHPG
      induced LTD involves activation of a protein tyrosine phosphatase.

PMID- 12213272
TI  - Multiple MPEP administrations evoke anxiolytic- and antidepressant-like effects
      in rats.
AB  - Several lines of evidence suggest a crucial involvement of glutamate in the
      mechanism of action of anxiolytic and antidepressant drugs. The involvement of
      group I mGlu receptors in anxiety and depression has also been proposed. In view
      of the recent discovery of anxiolytic- or antidepressant-like effects of acute
      injections of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective and brain
      penetrable mGlu5 receptor antagonist, we designed the present study to examine
      anxiolytic- and/or antidepressant-like effects of multiple administrations of
      this drug. The anxiolytic-like effects of MPEP were evaluated in rats using the
      conflict drinking test. The antidepressant-like effect was estimated using the
      rat olfactory bulbectomy model of depression. Seven subsequent injections of MPEP
      (1 mg/kg) significantly (by 320%) increased the number of shocks accepted during
      the experimental session in the Vogel test. MPEP given once daily at a dose of 10
      mg/kg, restored the learning deficit of bulbectomized rats after 14 days of
      treatment, remaining without any effect in the sham-operated animals. N-methyl-D
      aspartic acid (NMDA)-induced convulsions in mice were not affected by a single
      injection of MPEP (30 mg/kg) indicating that at this dose MPEP did not block NMDA
      receptors. The results indicate that the prolonged blockade of mGlu5 receptors
      exerts anxiolytic- and antidepressant-like effects in rats. No tolerance to
      anxiolytic-like action occurs. The previously mentioned results further indicate
      that antagonists of group I mGlu receptors may play a role in the therapy of both
      anxiety and depression.

PMID- 12213273
TI  - Astrocyte mGlu(2/3)-mediated cAMP potentiation is calcium sensitive: studies in
      murine neuronal and astrocyte cultures.
AB  - Signal transduction mechanisms of group II metabotropic glutamate receptors
      (mGlu(2/3)) remains a matter of some controversy, therefore we sought to gain new
      insights into its regulation by studying cAMP production in cultured neurons and
      astrocytes, and by examining inter-relationships of mGlu(2/3)-induced signalling
      with cellular calcium and various signalling cascades. mGlu(2/3) agonists 2R,4R-4
      aminopyrrolidine-2,4-dicarboxylic acid (2R,4R-APDC) and (-)-2-oxa-4
      aminobicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY379268) inhibited 10 microM
      forskolin-stimulated production of cAMP in murine cortical neurons, striatal
      neurons and forebrain astrocytes in the absence of extracellular Ca(2+). These
      agonists potentiated cAMP production in the presence of 1.8 mM Ca(2+) in
      astrocytes only. This potentiation was dependent on the extracellular Ca(2+)
      concentration (0.001-10 mM) and inhibited by the mGlu(2/3) antagonist LY341495 (1
      microM), adenosine deaminase (1 U/ml) and the adenosine A(2A) receptor antagonist
      ZM241385 (1 microM). Pre-incubation with the phospholipase C (PLC) inhibitor
      U73122 (10 microM), L-type Ca(2+)-channel blockers nifedipine (1 microM) and
      nimodipine (1 microM), the calmodulin kinase II (CaMKII) inhibitor KN-62 (10
      microM) or pertussis toxin (100 ng/ml) inhibited this potentiation. In the
      absence of 1.8 mM Ca(2+), thapsigargin (1 microM) facilitated the potentiation of
      cAMP production. Measurement of the Ca(2+)-binding dye Fluo-3/AM showed that,
      compared to Ca(2+)-free conditions, thapsigargin and 1.8 mM Ca(2+) elevated
      [Ca(2+)](i) in astrocytes; the latter effect being prevented by L-type Ca(2+)
      channel blockers. Potentiation of cAMP production was also demonstrated when
      astrocytes were stimulated with the beta-adrenoceptor agonist isoprenaline (10
      microM) in the presence of 1.8 mM Ca(2+), but not with the adenosine agonist NECA
      (10 microM) or the group I mGlu receptor agonist DHPG (100 microM). BaCl(2) (1.8
      mM) in place of Ca(2+) did not facilitate forskolin-stimulated mGlu(2/3)
      potentiation of cAMP. In short, this study in astrocytes demonstrates that under
      physiological Ca(2+) and adenylate cyclase stimulation an elevation of cAMP
      production is achieved that is mediated by PLC/IP(3)- and CaMKII-dependent
      pathways and results in the release of endogenous adenosine which acts at G(s)
      protein-coupled A(2A) receptors. These findings provide new insights into
      mGlu(2/3) signalling in astrocytes versus neurons, and which could determine the
      functional phenotypy of astrocytes under physiological and pathological
      conditions.

PMID- 12213274
TI  - Variation of CS salience reveals group II mGluR-dependent and -independent forms
      of conditioning in the rat.
AB  - There is good evidence that metabotropic glutamate receptors (mGluRs) are
      involved in some types of learning, and we have previously suggested that this
      involvement may reflect the modulation by mGluRs of the signal-to-noise ratio in
      neural networks. This hypothesis supposes that unspecific activation of mGluRs
      increases background noise level, so reducing the effectiveness of behaviourally
      relevant stimuli as signals in the network. We report here that intraperitoneal
      (i.p.) injection of 4-aminopyrrolidine-2,4-dicarboxylic acid (APDC), a specific
      agonist of group II mGluRs, disrupts conditioning to context (but not to cue)
      using conventional procedures. The hypothesis predicts, however, that the effect
      of the drug should be counteracted by the use of more salient stimuli, which
      would provide stronger signals to the network. In accordance with this
      prediction, we find that increases in the salience of either the CS (context) or
      the UCS (shock) abolish the drug-induced disruption of conditioning. These
      results suggest that group II mGluRs modulate neural networks involved in
      association formation.

PMID- 12213275
TI  - Differential regulation of synaptic transmission by mGlu2 and mGlu3 at the
      perforant path inputs to the dentate gyrus and CA1 revealed in mGlu2 -/- mice.
AB  - Group II metabotropic glutamate (mGlu) receptors can act as presynaptic
      autoinhibitory receptors at perforant path inputs to the hippocampus under
      conditions of high frequency synaptic activation. We have used mGlu2 -/- mice to
      examine the relative roles of mGlu2 and mGlu3 in the regulation of perforant path
      synaptic transmission mediated by both the selective group II receptor agonist,
      DCG-IV, and by synaptically released glutamate. Field excitatory postsynaptic
      potentials evoked by stimulation of either the perforant path inputs to the
      dentate gyrus mid-moleculare or the CA1 stratum lacunosum moleculare were
      inhibited by DCG-IV with IC(50) values and maximum percentage inhibition of: 169
      nM (60%) and 41 nM (72%) in wild-type mice and 273 nM (19%) and 116 nM (49%) in
      mGlu2 -/- mice, respectively. Activation of presynaptic group II mGlu
      autoreceptors by synaptically released glutamate, as revealed by a LY341495
      mediated increase in the relative amplitude of a test fEPSP evoked after a
      conditioning burst, was observed in both the dentate gyrus and the stratum
      lacunosum of wild-type, but not mGlu2 -/- mice. These observations demonstrate
      that activation of mGlu3 receptors can regulate synaptic transmission at
      perforant path synapses but suggest that mGlu2 is the major presynaptic group II
      autoreceptor activated by synaptically released glutamate.

PMID- 12213276
TI  - Modulation of lateral perforant path excitatory responses by metabotropic
      glutamate 8 (mGlu8) receptors.
AB  - The contribution of metabotropic glutamate 8 (mGlu8) receptors to modulation of
      medial and lateral perforant path (MPP and LPP) inputs to the dentate gyrus was
      investigated using electrophysiological recording of field excitatory
      postsynaptic potentials (fEPSPs) from hippocampal slices taken from wild-type and
      mGlu8 receptor knockout animals. Application of the selective group III mGlu
      receptor agonist, L-AP4 (1-100 microM), reduced fEPSPs evoked by LPP, but not MPP
      stimulation in wild-type slices in a concentration-dependent manner (EC(50) = 4.7
      microM). The selective mGlu8 receptor agonist, DCPG (1-30 microM) also suppressed
      LPP fEPSPs with an EC(50) value of 3.1 microM. The L-AP4-induced reduction in LPP
      fEPSPs could be blocked by the group III antagonist, MSOP (100 microM) in wild
      type slices and was eliminated in mGlu8 receptor-deficient slices. Additional
      experiments showed that MPP fEPSPs were suppressed by the group II agonist,
      LY379268 (0.01-3 microM) in control slices (EC(50) = 153.1 nM); an effect that
      was not altered in mGlu8 receptor knockout slices (EC(50) = 153.8 nM). In
      addition, LY379268 had little effect on fEPSPs evoked by LPP stimulation in mGlu8
      receptor-deficient slices. In conjunction with recent receptor localization
      studies, these results suggest that the mGlu8 receptors serve as autoreceptors on
      LPP afferents to the dentate gyrus.

PMID- 12213277
TI  - Reduction of excitatory transmission in the retino-collicular pathway via
      selective activation of mGlu8 receptors by DCPG.
AB  - We have previously shown that activation of Group III metabotropic glutamate
      (mGlu) receptors modulates synaptic transmission in the superior colliculus. We
      thus investigated the effect of the selective mGlu8 receptor agonist (S)-3,4
      dicarboxyphenylglycine (DCPG) on excitatory synaptic transmission in the
      superficial superior colliculus (SC) using an in vitro slice preparation of the
      rat SC. Field EPSPs evoked by optic tract stimulation under conditions of GABA
      receptor blockade were reduced by DCPG by up to 67.8+/-5.46% (EC(50) 1.25+/-0.56
      microM), and this effect could be antagonised by LY341495 at a concentration (300
      nM) known to be effective at mGlu8 receptors but not at mGlu4 or mGlu7 receptors.
      The broad-spectrum (mGlu4/mGlu7/mGlu8) agonist L-2-amino-4- phosphonobutyric acid
      (L-AP4) produced similar reductions of synaptic transmission (maximal reduction
      68.6+/-2.33%; EC(50) 5.7+/-2.61 microM). These data are consistent with previous
      results which show that mGlu8 receptor activation can reduce synaptic
      transmission in the spinal cord, and indicate that similar mechanisms operate in
      other brain areas. Furthermore, this indicates that the mGlu8 receptor may have a
      role in the modulation of visual transmission in the superior colliculus.

PMID- 12213278
TI  - Performance deficits of mGluR8 knockout mice in learning tasks: the effects of
      null mutation and the background genotype.
AB  - mGluR8 is a G-protein coupled metabotropic glutamate receptor expressed in the
      mammalian brain. Members of the mGluR family have been shown to be modulators of
      neural plasticity and learning and memory. Here we analyze the consequences of a
      null mutation at the mGluR8 gene locus generated using homologous recombination
      in embryonic stem cells by comparing the learning performance of the mutants with
      that of wild type controls in the Morris water maze (MWM) and the context and cue
      dependent fear conditioning (CFC). Our results revealed robust performance
      deficits associated with the genetic background, the ICR outbred strain, in both
      mGluR8 null mutant and the wild type control mice. Mice of this strain origin
      suffered from impaired vision as compared to CD1 or C57BL/6 mice, a significant
      impediment in MWM, a visuo-spatial learning task. The CFC task, being less
      dependent on visual cues, allowed us to reveal subtle performance deficits in the
      mGluR8 mutants: novelty induced hyperactivity and temporally delayed and blunted
      responding to shocks and temporally delayed responding to contextual stimuli were
      detected. The role of mGluR8 as a presynaptic autoreceptor and its contribution
      to cognitive processes are hypothesized and the utility of gene targeting as
      compared to pharmacological methods is discussed.

PMID- 12213279
TI  - Increased anxiety-related behavior in mice deficient for metabotropic glutamate 8
      (mGlu8) receptor.
AB  - Pre-synaptic metabotropic glutamate (mGlu) receptors modulate neuronal
      excitability by controlling glutamate and gamma-aminobutyric acid (GABA) release.
      The mGlu8 receptor is predominantly found in pre-synaptic terminals and its
      expression is highly restricted. To study the role of this receptor, mGlu8
      receptor-deficient mice were generated. Here we report that naive mGlu8 receptor
      deficient mice showed increased anxiety-related behavior in the elevated plus
      maze in low illumination conditions (red light). Open arm avoidance and risk
      assessment behavior were both significantly increased in mutant mice. Increased
      stressfulness of the testing conditions abolished this behavioral difference.
      Fluorescent light or prior restraint stress decreased the open arm activity of
      wild-type mice, while the open arm activity of mutant mice was essentially
      unaffected, leading to similar values in both strains. The total number of arm
      entries or closed arm entries was not significantly different between strains,
      indicating that the lack of mGlu8 receptor does not affect locomotor activity. No
      gross behavioral changes, or changes in the function of the autonomic nervous
      system or somatomotor systems were observed in mutant mice. Moreover, no
      significant differences in seizure susceptibility were detected between strains.
      Our results suggest that mGlu8 receptor may play a role in responses to novel
      stressful environment.

PMID- 12213280
TI  - Changes in metabotropic glutamate receptor 1-8 gene expression in the rodent
      basal ganglia motor loop following lesion of the nigrostriatal tract.
AB  - Metabotropic glutamate (mGlu) receptors in the basal ganglia motor loop may
      increase cell excitability (Group I) or modulate neurotransmitter release (Group
      I, II and III). Nigrostriatal tract degeneration in Parkinson's disease (PD)
      produces downstream pathological disturbances in glutamate and GABA transmission.
      The present study examined whether changes in mGlu receptor gene expression may
      either contribute to, or compensate for these pathological changes in
      transmission. In situ hybridisation studies examined the levels of mGlu receptor
      mRNA in motor loop regions in rats bearing a 6-hydroxydopamine-induced unilateral
      nigrostriatal tract lesion. Gene expression was reduced in the lesion compared to
      intact hemispheres for mGlu(1) in the substantia nigra pars compacta (SNc; 51.8+/
      11.5%), mGlu(3) in the striatum and globus pallidus (11.7+/-2.8% and 18.9+/-1.4%,
      respectively) and mGlu(4) in the striatum and premotor cortex (13.8+/-2.7% and
      15.8+/-5.5%, respectively). Loss of mGlu(1) mRNA in the SNc confirms that mGlu(1)
      is highly expressed on dopaminergic neurones where it may contribute to their
      vulnerability in PD. The down-regulation of mGlu(3) and mGlu(4) mRNA may reflect
      reduced transcriptional activity in response to increased levels of extracellular
      glutamate in these regions under parkinsonian conditions. These changes are
      likely to exacerbate the pathophysiological glutamate and GABA transmission
      within these regions in PD.

PMID- 12213282
TI  - Inhibitory effect of glycolic acid on ultraviolet B-induced c-fos expression, AP
      1 activation and p53-p21 response in a human keratinocyte cell line.
AB  - Glycolic acid, an alpha-hydroxy acid derived from fruit and milk sugars, has been
      commonly used as a cosmetic ingredient since it was known to have photo
      protective and anti-inflammatory effects, and anti-oxidant effect in UV
      irradiated skin. However, little has been known about the functional role of
      glycolic acid on UV-induced skin tumorigenesis. We previously found that glycolic
      acid inhibited UV-induced skin tumor development in hairless mouse. In this study
      we investigated anti-tumor promoting mechanism of glycolic acid on the UV-induced
      skin tumor development. The ability of glycolic acid to inhibit the UVB-induced
      cytotoxicity, apoptosis and expression of apoptosis-regulatory genes (p53 and
      p21) was examined. We also investigated whether glycolic acid could inhibit UVB
      induced alternation of cell cycle, c-fos expression and activation of
      transcription factor AP-1 in cultured immortalized human keratinocyte HaCaT
      cells. Glycolic acid treatment attenuated the UVB-induced cell cytotoxicity as
      well as apoptosis. Glycolic acid also inhibited the UVB-induced expression of c
      fos and the activation of transcription factor AP-1, and inhibited mRNA levels of
      apoptosis-regulatory gene (p53 and p21). These results suggest that glycolic acid
      may exert the inhibitory effect on the UVB-induced skin tumor development by
      blocking the UVB-induced of apoptosis and cytotoxicity through inhibition of c
      fos expression and activation of AP-1 in addition to the inhibition of p53-p2l
      response pathway.

PMID- 12213283
TI  - Squamous cell carcinoma of the tongue: the prevalence and prognostic roles of
      p53, Bcl-2, c-erbB-2 and apoptotic rate as related to clinical and pathological
      characteristics in a retrospective study.
AB  - In the current study, we examined the clinical characteristics and survival
      probability rates of 116 patients treated for squamous cell carcinoma (SCC) of
      the tongue. In 55 randomly selected patients these data were correlated with the
      immunohistological analysis of the tumor and apoptosis-related markers, p53, Bcl
      2, c-erbB-2 (Her-2/neu), and to the apoptosis rate assessment by the terminal
      dUTP nick-end-labeling (TUNEL) method. The overall 5-year survival probability
      was 55%, which might be the result of the low incidence of smoking and/or alcohol
      consumption among the patients (21%), the early diagnosis (65% at Stages I-II)
      and the low histological grades (91% good-moderate). Radiotherapeutic or surgical
      treatment of the neck did not alter the survival probability achieved by local
      surgery for Stage I patients, but significantly improved survival for Stage II
      patients. Independent tumor-related variables which significantly worsened the
      probability of survival were found. Concomitant non-oral cancer was found to be a
      poor variable for prognosis prediction. Positive staining of p53, TUNEL
      (apoptosis rate), c-erbB-2 and Bcl-2 was found in 60, 48, 18 and 15% of the
      lesions, respectively (P<0.0001). The possible biological significance of these
      markers in tongue SCC is discussed in relation to the current literature, and an
      independent role for TUNEL and p53 is suggested.

PMID- 12213284
TI  - High cytotoxicity of alpha-tocopheryl hemisuccinate to cancer cells is due to
      failure of their antioxidative defense systems.
AB  - Alpha-tocopheryl hemisuccinate (TS) has been reported to induce apoptosis in
      various cells, and to show higher toxicity to cancer cells than to normal cells.
      In this study, although TS induced apoptosis in both a mouse breast normal cell
      line NMuMG and a mouse breast cancer cell line C127I, the latter were more
      susceptible to TS. TS-induced apoptosis in C127I was inhibited by superoxide
      dismutase, alpha-tocopherol and butylated hydroxyanisol. From these results,
      superoxide (O(2)(-)) itself and reactive oxygen species derived from O(2)(-)
      and/or free radicals are assumed to be associated with TS toxicity, and the high
      toxicity of TS to cancer cells is suggested to be due to failure of their
      antioxidative defense systems.

PMID- 12213285
TI  - Down-regulation of invasion and angiogenesis-related genes identified by cDNA
      microarray analysis of PC3 prostate cancer cells treated with genistein.
AB  - Prostate cancer is the second leading cause of cancer related deaths in men in
      the United States and for many years the treatment results for metastatic
      prostate cancer have been disappointing. Our previous studies have shown that
      genistein elicits pleiotropic effects on prostate cancer cells; however, its role
      in invasion and metastasis has not been fully elucidated. In order to better
      understand the precise molecular mechanism(s) by which genistein exerts its
      effects on PC3 cells, we have utilized cDNA microarray to interrogate 12558 known
      genes to determine the gene expression profile altered by genistein treatment. We
      found a total of 832 genes which showed >2-fold change after genistein treatment.
      Among these genes, we found down-regulation of 11 genes (MMP-9, protease M, uPAR,
      VEGF, neuropilin, TSP, BPGF, LPA, TGF-beta2, TSP-1, PAR-2) and up-regulation of
      two genes (connective tissue growth factor, connective tissue activation
      peptide), which are related to angiogenesis, tumor cell invasion and metastasis.
      Reverse transcription-polymerase chain reaction, Western blot, and zymographic
      analysis were conducted to confirm the data of microarray at the level of mRNA,
      protein, and biological function. The results were in direct agreement with the
      microarray data. From these results, we conclude that genistein down-regulates
      the transcription and translation of genes critically involved in the control of
      angiogenesis, tumor cell invasion and metastasis, suggesting the possible
      therapeutic role of genistein for metastatic prostate cancer. Thus, genistein
      induced alternations of gene expressions may be exploited for devising
      chemopreventive or therapeutic strategies, particularly for chemosensitization of
      metastatic prostate cancer to existing chemotherapeutic agents.

PMID- 12213286
TI  - Resistance to mammary carcinogenesis in Copenhagen rats: potential roles of
      vascular endothelial growth factor and mast cells.
AB  - The Copenhagen (COP) rat is extremely resistant to mammary cancer induction by
      carcinogens. Multiple genetic loci have been linked to the resistant phenotype,
      but the mechanisms underlying the resistance still remain unknown. Evidence has
      shown that the acquisition of angiogenic capacity is critical for tumor
      development. We, therefore, decided to investigate whether administration of
      angiogenic factor would enhance mammary carcinogenesis in the COP rat. Vascular
      endothelial growth factor (VEGF) was administered in a sustained releasing
      formula to pubescent female COP rats 2 weeks after N-nitroso-N-methylurea (NMU)
      treatment. Six months after NMU exposure, we found no difference in mammary tumor
      incidence between VEGF treated animals and controls. Analysis of VEGF expression,
      however, revealed different expression patterns in mammary epithelial cells of
      various origins. Mammary epithelial cells from pubescent susceptible Buffalo
      (BUF) and COP rats expressed substantial levels of VEGF messages, whereas cells
      prepared from 230-day-old rats showed negligible levels of VEGF mRNA. We also
      demonstrated that mammary epithelial cells from tumors developed in susceptible
      BUF rats expressed VEGF, whereas VEGF messages were barely detectable in tumors
      induced in COP rats. Furthermore, enlargement of the intramammary lymph nodes
      with prominent mast cells was observed in NMU treated COP rats, but not in NMU
      treated BUF rats. These results suggest that down regulation of VEGF expression
      is insufficient for resistance to mammary carcinogenesis, and that enhanced
      immune response, as evidenced by intramammary lymph node enlargement with mast
      cell accumulation, may also play a role in conferring resistance in the COP rat.

PMID- 12213287
TI  - Purging effect of dibutyl phthalate on leukemia cells involves fas independent
      activation of caspase-3/CPP32 protease.
AB  - We previously found that dibutyl phthalate (DBP) had a pharmacological activity
      in eliminating tumor cells and could be used as a purging agent in autologous
      bone marrow transplantation. In this study, we show that DBP can induce apoptosis
      in MO7e and U937 leukemia cell lines. Treatment of these cells with DBP up
      regulates cellular activity of caspase-3/CPP32 and causes apoptosis rapidly as
      determined by cell viability and dUTP nick end labeling assay. Activation of
      caspase-3/CPP32 and cleavage of poly(ADP-ribose) polymerase were determined in
      DBP-induced apoptosis of leukemia cells. However, DBP treatment did not induce
      the expression of fas. Two caspase inhibitors, z-VAD-fmk and N-acetyl-Asp-Glu-Val
      Asp-aldehyde partly blocked the cell death of MO7e cells induced by DBP. These
      results suggest that fas-independent activation of caspase-3 protease plays
      important roles in the purging effect of DBP on leukemia cells.

PMID- 12213288
TI  - Immunophenotypical markers, ultrastructure and chemosensitivity profile of
      metastatic melanoma cells.
AB  - The survival of patients affected by cutaneous melanoma has improved dramatically
      in the last 10 years, because of earlier diagnosis. Despite this, the therapeutic
      results obtained in metastatic melanoma (MM) are very disappointing due to its
      poor responsiveness to cytotoxic agents. In this type of solid tumor, tumor
      chemosensitivity assays have been suggested to be an important tool to predict
      clinical responsiveness to therapy. Metastatic melanoma cells (MMCs) were
      obtained from subcutaneous melanoma metastases of five patients and cultured for
      several consecutive passages. An immunofluorescence and an electron microscopic
      study were performed in order to establish the ultrastructural and
      physiopathological features of MMCs. A sulphorodamine-B test was used to measure
      in vitro sensitivity of MMCs to temozolomide, cisplatin, vindesine, taxol and
      interpheron alpha-2a. Following a 72 h exposure, maximum activity was obtained
      with vindesine (median inhibitory concentration, IC(50), 0.23 nM) and taxol
      (median IC(50) 0.31 nM). Cisplatin median IC(50) values were higher (4.6 microM)
      than taxol and vindesine, but still in the range of clinically achievable plasma
      concentrations. Temozolomide inhibited cell proliferation only at very high
      concentrations (median IC(50) 228 microM). No significant cell growth inhibitory
      effects (<or=25%) were observed with interferon alpha-2a concentrations up to
      8000 IU/ml. MMCs expressed progression markers typical of cutaneous metastatic
      melanoma and showed poor sensitivity in vitro to most anticancer drugs tested,
      including temozolomide.

PMID- 12213289
TI  - Lifestyle habits and genetic susceptibility and the risk of esophageal cancer in
      the Thai population.
AB  - The association of lifestyle habits and polymorphism of ADH2 and ALDH2 genes with
      the risk of esophageal cancer in Thai population was investigated in a hospital
      based case-control study: 202 cases and 261 controls. The results of multivariate
      logistic analysis showed that alcohol consumption >60g/day, smoking >10
      cigarettes/day and chewing betel >or=10 quids/day significantly increased risk
      (odds ratio (OR) 5.84, 95% confidence interval (CI) 3.15-10.83; 4.65, 95% CI 1.99
      10.84; and 4.68, 95% CI 2.05-10.72, respectively). ADH2*1/*1 also increased the
      risk significantly (OR 1.56, 95% CI 1.01-2.39) while ALDH2 did not (OR of
      ALDH2*1/*2 1.57, 95% CI 0.89-2.76). However, the combined at risk genotypes,
      ADH2*1/*1 and ALDH2*1/*2 increased risk to four-fold. In addition, significant
      gene-environment interaction was found. Heavy drinkers >60g/d harboring ADH2*1/*1
      or ALDH2*1/*2 had about an 11-fold increased risk.

PMID- 12213290
TI  - Characterization of sperm protein 17 in human somatic and neoplastic tissue.
AB  - Sperm protein 17 (Sp17) is a highly antigenic, testes-specific protein whose
      known function is to bind sperm to the zona pellucida. However, the Sp17 gene has
      been recently detected in normal non-testes tissues and malignant neoplasias. As
      the role of Sp17 in non-testes tissues is unknown, the characterization of the
      Sp17 gene in highly proliferating tissues may provide further insight into the
      regulation and alternative function of Sp17. Reverse transcriptase-polymerase
      chain reaction (RT-PCR) was used to amplify the Sp17-1 transcript in multiple
      normal human tissues and cancer cell lines. Similarly, the Sp17-2 gene was
      examined by PCR. In addition, Northern and Western blot analyses were used to
      detect Sp17 mRNA and protein expression. The Sp17-1a and Sp17-1b transcripts were
      amplified from cancer cell lines. Similarly, an Sp17-2 transcript was also
      detected in cancer cell lines. Furthermore, Northern blot analysis revealed Sp17
      mRNA expression in all cancer cell lines examined. However, Sp17 protein
      expression was not detected. The differential detection of the Sp17 transcripts
      in cancer cell lines as compared to normal non-testes tissues, suggests a
      potential pathogenic role for Sp17 in diseased cells. Moreover, the Sp17-2
      transcript may be a marker for highly proliferating cells. Collectively, these
      data implicate Sp17 as a cancer testis antigen.

PMID- 12213291
TI  - 4-Fluoro-N-butylphenylacetamide: a synthetic phenylacetate derivative that
      upregulates Bcl-X(S), activates caspase cascade and induces apoptosis in human
      squamous lung cancer CH27 cells.
AB  - Phenylacetate (PA) and related aromatic fatty acids induce antiproliferation and
      differentiation of cancer cell; they have potent anti-tumor properties with
      relatively low toxicity. To search for more potent analogues of PA, PA
      derivatives have been synthesized. In this study, we investigated the effects of
      six synthetic PA derivatives on the growth of human lung cancer cells. Results
      showed that the anti-proliferative effects of these synthetic compounds were
      strong than those of PA, 4-fluoro-N-butylphenylacetamide (H6) is the most potent
      compound. 4,6-Diamidino-2-phenylindole (DAPI) staining, in situ TUNEL assay and
      DNA gel electrophoresis analysis indicated that a marked reduction in the number
      of CH27 cells with H6 was related to the induction of apoptosis. The apoptosis
      triggered by H6 was accompanied by up-regulation of Bcl-X(S), accumulation of
      cytosolic cytochrome c and activation of caspase cascade (caspase-9 and -3).
      Furthermore, H6 induces proteolytic cleavage of poly (ADP-ribose) polymerase,
      which followed the appearance of caspase activity and preceded DNA fragmentation.
      Pretreatment with caspase inhibitors markedly inhibited H6-induced caspase
      activity and apoptosis. These results suggest that H6 may induce apoptosis
      through a Bcl-X(S) and caspase-dependent mechanism.

PMID- 12213292
TI  - Influence of adjuvant tamoxifen treatment on bone mineral density and bone
      turnover markers in postmenopausal breast cancer patients in Japan.
AB  - The effect of adjuvant tamoxifen treatment on bone mineral density (BMD) and bone
      turnover markers was studied in postmenopausal breast cancer patients. The
      relationship of tamoxifen's effect with the genetic polymorphisms of estrogen
      receptor (ER)-alpha and ER-beta gene was also studied. Twenty-one postmenopausal
      breast cancer patients were given tamoxifen (20 mg/day) as the adjuvant treatment
      after the surgery. BMD of the lumbar supine (dual emission X-rays absorptiometry)
      and bone resorption (deoxypyridinoline, aminoterminal telopeptide of type I
      collagen, and carboxyterminal telopeptide of type I collagen) and formation
      (propeptide of type I procollagen, osteocalcin, and bone-specific alkaline
      phosphatase) markers were examined at baseline (before the surgery), 6 and 12
      months after the start of tamoxifen treatment. Genetic polymorphisms analyzed
      were TA dinucleotide repeats polymorphism in the promoter region and PvuII and
      XbaI restriction fragment length polymorphism for the ER-alpha gene and the CA
      dinucleotide repeats polymorphism in the intron 5 for the ER-beta gene. Tamoxifen
      significantly increased BMD of the lumbar spine at both 6 (P<0.01) and 12 months
      (P<0.01) after the start of tamoxifen as compared with that at baseline. The mean
      percent increase in BMD was 3.3% at 6 months and 2.7% at 12 months. All bone
      resorption and formation markers significantly decreased at both 6 and 12 months.
      Among the four genetic polymorphisms studied, only ER-beta CA repeat polymorphism
      was found to be significantly associated with BMD at 12 months, i.e. BMD of the
      21 CA repeats allele carriers was significantly higher than that of the non
      carriers (P=0.025). These results suggest that tamoxifen increases BMD of the
      lumbar supine by reducing the bone turnover in postmenopausal breast cancer
      patients, and this bone restoring effect of tamoxifen is more marked in ER-beta
      21 CA repeats allele carriers than non-carriers.

PMID- 12213293
TI  - Expression of TGF-beta type I and II receptors in normal and cancerous human
      endometrium.
AB  - Transforming growth factor-beta (TGF-beta) belongs to a superfamily of
      structurally related polypeptides involved in various biological processes,
      including cell growth, proliferation and differentiation, angiogenesis,
      apoptosis, and extracellular matrix remodeling. We tried to define the different
      expression patterns of the TGF-beta receptors by investigating the female
      reproductive organs during the menstrual cycle and endometrial tumorigenesis,
      because their role in these processes is still unclear. In this study, we
      examined the expression of the TGF-beta type I and type II receptors in normal
      (n=13) and carcinomatous (n=42) endometrial tissue specimens using reverse
      transcriptase polymerase chain reaction and immunological (Western blot and
      enzyme linked immunosorbent assay) methods. Two uncommon female genital tract
      tumors, rhabdomyosarcoma of the uterine cervix and uterine carcinosarcoma, were
      also included. There were no significant differences between normal and cancerous
      endometrial tissues regarding the TGF-beta receptors mRNA levels. However, we
      observed a markedly low TGF-beta type I receptor protein level (P<0.028; Mann
      Whitney-U test), while the malignant endometrium showed a significantly higher
      TGF-beta type II receptor protein level (P<0.007; Mann-Whitney-U test) than the
      normal endometrium. Moreover, significantly elevated TGF-beta receptor type II
      protein level was noted when depth of myometrial invasion of endometrial
      carcinomas was considered (P<0.05; Mann-Whitney-U test). In contrast to uterine
      carcinosarcoma, in which no detectable mRNA for TGF-beta type II receptor was
      found, we noted expression of both TGF-beta receptors in rhabdomyosarcoma of the
      uterine cervix. However, neither rhabdomyosarcoma of the uterine cervix nor
      uterine carcinosarcoma displayed TGFbetaRI and TGFbetaRII protein expression.
      This observation corroborates the complexity of the deregulation of TGF-beta
      receptor expression in human endometrial cancer.

PMID- 12213294
TI  - Avian brainstem neurogenesis is stimulated during cochlear hair cell
      regeneration.
AB  - Unlike mammals, adult avians are able to regenerate cochlear sensory hair cells
      following injury. Brainstem auditory neurons in chicken nucleus magnocellularis
      (NM), which receive their sole excitatory afferent input from the cochlea, were
      examined for evidence of mitosis during ototoxin-induced loss and regeneration of
      cochlear hair cells. Using tritiated thymidine as a mitotic marker in tissue
      processed for autoradiography and counterstained with thionin, labeled NM neurons
      and glia were counted from chickens killed 16 days after gentamicin or saline
      injections. Newly generated NM neurons were observed during cochlear hair cell
      regeneration. More labeled neurons were observed in the experimental chickens,
      but a few were also seen in the control chickens. We predicted labeled NM neurons
      would be found solely in the rostral high frequency region, given the gentamicin
      induced high frequency cochlear hair cell loss and regeneration. However, the
      labeled NM neurons were located throughout the tonotopic axis of the nucleus. The
      total number of labeled neurons was lower than predicted. Many labeled NM glia
      were observed in experimental and control chickens. Labeled cells were also
      observed throughout the chicken brainstem and cerebellum in both experimental and
      control chickens, indicating great potential for CNS plasticity. Results in NM
      indicate the avian auditory system is capable of regenerating brainstem auditory
      neurons in addition to the previously well-established capability of regenerating
      cochlear hair cells in response to ototoxic injury. Recovery of both central and
      peripheral auditory components will be necessary to restore hearing damaged by
      noise or ototoxic drugs.

PMID- 12213295
TI  - Hsp70 and Hsp40 improve neurite outgrowth and suppress intracytoplasmic aggregate
      formation in cultured neuronal cells expressing mutant SOD1.
AB  - Mutations of the superoxide dismutase 1 (SOD1) gene cause familial amyotrophic
      lateral sclerosis (FALS). Intracytoplasmic aggregate formation consisting of
      mutant SOD1 is the histological hallmark of FALS. Since a previous report
      revealed that Hsp70 reduced aggregate formation and cell death in a cell model of
      FALS, here we examined the combined effects of Hsp70 and its cofactor, Hsp40, on
      a cell model of FALS. The combination of Hsp70 and Hsp40 reduced intracytoplasmic
      aggregates and markedly improved neurite outgrowth. They also prevented cell
      death to a relatively lesser extent. Neurite outgrowth was recognized almost
      exclusively in the cells without intracytoplasmic aggregates. Hsp70 and Hsp40
      were upregulated in cells expressing mutant SOD1, and were colocalized with
      intracytoplasmic aggregates of mutant SOD1. These findings suggest that heat
      shock proteins (HSPs) promote neurite outgrowth by suppressing intracytoplasmic
      aggregate formation and restoring cellular dysfunctions. This is the first
      demonstration that overexpression of HSPs improved neurite outgrowth as it
      suppressed intracytoplasmic aggregate formation and cell death in a cultured
      neuronal cell model of FALS. These findings may provide a basis for the
      utilization of HSPs in developing a treatment for FALS.

PMID- 12213296
TI  - Cortico-cortical projections of the motorcortical larynx area in the rhesus
      monkey.
AB  - The efferent cortico-cortical projections of the motorcortical larynx area were
      studied in three rhesus monkeys (Macaca mulatta), using biotin dextranamine as
      anterograde tracer. Identification of the larynx area was made with the help of
      electrical brain stimulation and indirect laryngoscopy. Heavy projections were
      found into the surrounding ventral and dorsal premotor cortex (areas 6V and D),
      primary motor cortex (area 4), the homolog of Broca's area (mainly area 44),
      fronto- and parieto-opercular cortex (including secondary somatosensory cortex),
      agranular, dysgranular and granular insula, rostral-most primary somatosensory
      cortex (area 3a), supplementary motor area (area 6M), anterior cingulate gyrus
      (area 24c) and dorsal postarcuate cortex (area 8A). Medium projections could be
      traced to the ventrolateral prefrontal and lateral orbital cortex (areas 47L and
      O), the primary somatosensory areas 3b and 2, the agranular and dysgranular
      insula, and the posteroinferior parietal cortex (area 7; PFG, PG). Minor
      projections ended in the lateral and dorsolateral prefrontal cortex (areas 46V
      and 8B), primary somatosensory area 1 and cortex within the intraparietal sulcus
      (PEa) and posterior sulcus temporalis superior (TPO). Due to its close spatial
      relationship to the insula on the one hand and the premotor cortex on the other,
      the larynx area shows projections which, in some respects, are not typical for
      classical primary motor cortex.

PMID- 12213297
TI  - Hypersensitivity of dopamine transmission in the rat striatum after treatment
      with the NMDA receptor antagonist amantadine.
AB  - Amantadine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist
      known to increase dopamine synthesis and release in the striatum, is frequently
      associated with L-DOPA in the treatment of Parkinson's disease. However, the
      biochemical mechanisms involved in the effect of amantadine and the consequences
      of its repetitive administration on the modulation of striatal dopamine
      transmission still need to be clarified. We have investigated the effects of
      short-term amantadine treatments on the expression of dopamine receptors and the
      functional coupling to G proteins in rat striatal membranes. Dopamine-induced
      stimulation of guanosine 5'-[gamma-35S]triphosphate ([35S]GTPgammaS) binding was
      significantly enhanced (40%) in striatum homogenates from rats treated for 4 days
      with amantadine (40 mg/kg, i.p.) compared to vehicle-treated animals. This effect
      was specific for dopamine receptors and was transient as no significant
      modifications were observed when animals were treated for either 2 or 7 days.
      Administration of amantadine did not directly affect the animal behaviour.
      However, treated animals exhibited hypersensitive dopamine transmission since
      rats treated for 4 days showed exacerbated responses to a single apomorphine
      administration (enhanced locomotor activity and reduced stereotypy). Since the
      effects of amantadine administration differ from those usually observed with
      direct dopamine receptor agonists or other NMDA receptor antagonists, we suggest
      that multiple biochemical mechanisms contribute to the modulation of dopamine
      transmission by amantadine.

PMID- 12213298
TI  - Forebrain circumventricular organs mediate salt appetite induced by intravenous
      angiotensin II in rats.
AB  - Two circumventricular organs, the subfornical organ (SFO) and organum vasculosum
      laminae terminalis (OVLT), may mediate salt appetite in response to acute
      intravenous infusions of angiotensin (ANG) II. Fluid intakes and mean arterial
      pressures were measured in rats with sham lesions or electrolytic lesions of the
      SFO or OVLT during an intravenous infusion of 30 ng/min ANG II. Beginning 21 h
      before the 90-min infusion, the rats were depleted of sodium with furosemide and
      given a total of 300 mg/kg captopril in 75 ml/kg water in three spaced gavages to
      block the usual salt appetite and to hydrate the rats. No other food or fluids
      were available for ingestion. Sham-lesioned rats drank 9.3+/-1.2 ml if 0.3 M NaCl
      alone was available and drank 8.9+/-1.6 ml of saline and 3.7+/-1.6 ml of water if
      both were available. Either SFO or OVLT lesions reduced the intakes of saline to
      <5 ml in both conditions and of water to <1 ml. Mean arterial pressure did not
      differ among the groups and was maintained above 100 mmHg after the depletion and
      captopril treatments because of the large doses of water. Thus, a full expression
      of salt appetite in response to an acute intravenous infusion of ANG II requires
      the integrity of both the SFO and OVLT.

PMID- 12213299
TI  - Evaluation of changes in methylmercury accumulation in the developing rat brain
      and its effects: a study with consecutive and moderate dose exposure throughout
      gestation and lactation periods.
AB  - Methylmercury (MeHg) can be transferred to the fetus through the placenta and to
      newborn offspring through breast milk. The higher mercury (Hg) accumulation and
      susceptibility to toxicity in the fetus than in the mother during the gestation
      period is well known. However, the contribution of MeHg exposure through breast
      milk to the brain Hg concentration in offspring is not clear. The purposes of
      this study were to evaluate the changes in Hg concentration in the brain of
      offspring and its effects on the developing rat brain, based on consecutive and
      moderate doses of MeHg throughout gestation and lactation. Adult female rats were
      given a diet containing 5 ppm Hg (as MeHg) for 8 weeks. The administration level
      was thought not to cause adverse effects in adult rats. The rats were then mated
      and subsequently given the same diet throughout gestation and after parturition.
      The newborn offspring were placed with the mothers until postnatal day 30. The
      offspring were exposed to MeHg throughout their intrauterine life through the
      placenta, and during the postnatal developing phase via contaminated milk.
      Furthermore, they were given the same diet containing MeHg for 2 months following
      weaning. On the day of parturition, the concentration of Hg in the brains of
      newborns was 1.4 times higher than that in the mothers. During the suckling
      period the concentration in the brain of the offspring rapidly declined to 1/5 of
      that at birth, suggesting that MeHg transport by milk was limited while the brain
      and body volumes increased rapidly. The concentration increased gradually again
      after the offspring started the contaminated diet. In behavioral tests performed
      at 5 and 6 weeks of age, MeHg-exposed rats showed a significant deficit in motor
      coordination in the rotarod test and a learning disability in the passive
      avoidance response test, compared with controls. Histopathologically, focal
      cerebellar dysplasia, including the heterotopic location of Purkinje cells and
      granule cells, was observed. These abnormalities may be induced by the effect of
      highly accumulated MeHg in the brain during the gestation period. Thus, although
      offspring are subjected to consecutive and moderate dose MeHg exposure throughout
      both the gestation and suckling periods, the risk is especially high during
      gestation but may decrease during lactation.

PMID- 12213300
TI  - Dorsal and ventral hippocampal cholinergic systems modulate anxiety in the plus
      maze and shock-probe tests.
AB  - There is emerging evidence that increased acetylcholine levels in brain reduce
      anxiety. More specifically there is evidence that some of these anxiolytic
      effects of acetylcholine are modulated by the hippocampus. In the present study
      we examined the roles of the cholinergic systems in the dorsal and ventral
      hippocampus in two animal models of anxiety: the elevated plus-maze and the shock
      probe burying tests. We found that microinfusions (10 microg/0.5 microl) of the
      acetylcholinesterase inhibitor physostigmine in either the dorsal or the ventral
      hippocampus increased rats' open arm exploration in the plus-maze test, and
      decreased burying behavior in the shock-probe test. Interestingly, infusions in
      the ventral, but not the dorsal hippocampus also increased the number of contacts
      rats made with the shock-probe. Overall, the results suggest that cholinergic
      stimulation in the dorsal and ventral hippocampus modulate anxiety, but that only
      the ventral hippocampal cholinergic system is involved in the passive avoidance
      of painful stimuli.

PMID- 12213301
TI  - Immunological challenge modulates brain orphanin FQ/nociceptin and nociceptive
      behavior.
AB  - Orphanin FQ/Nociceptin (OFQ/N), an endogenous peptide found throughout the
      central nervous system, has been attributed with a wide range of functions,
      including modulation of motivational and emotional behavior, but most
      prominently, facilitation of hyperalgesia. It has also been shown that brain
      OFQ/N is stimulated during locally-induced peripheral inflammation, a condition
      well known to increase pain sensitivity. However, few studies have addressed
      whether specific immunological challenge using T-cell dependent and independent
      stimuli alters OFQ/N gene activation in the brain. Consequently, male C57BL/6J
      mice were challenged with 5 microg of lipopolysaccharide (LPS) or a T-cell
      activating bacterial superantigen, Staphyloccocal enterotoxin A (SEA), and levels
      of brain OFQ/N precursor, pNOC, mRNA were analyzed by semi-quantitative RT-PCR.
      In addition, nociceptive thresholds were examined in immunologically challenged
      mice using the hotplate test. Initial results on a combined region of the brain
      containing various limbic components, revealed increased levels of pNOC mRNA in
      response to SEA challenge, but not to LPS. Further analysis of more discrete
      brain regions revealed increased pNOC mRNA in the hypothalamus and amygdala in
      response to SEA. Interestingly, challenge with SEA, but not LPS, significantly
      reduced hindpaw-lick latency in the hot plate test, although this effect was
      observed only if the hotplate environment was unfamiliar, suggesting an
      interaction between immunological stimulation and novelty-induced stress. Since
      SEA induces various cytokines, including TNF-alpha, these results are consistent
      with a growing literature documenting the effects of cytokines on nociceptive
      functions, and a possible involvement of the OFQ/nociceptin system.

PMID- 12213302
TI  - Neuropeptide Y potentiates the pressor response evoked by carbachol
      administration into the posterior hypothalamic nucleus of conscious rat.
AB  - The unilateral microinjection of the cholinergic agonist carbachol (CCh) or the
      biologically active peptide neuropeptide Y (NPY) into the posterior hypothalamic
      nucleus (PHN) of conscious, freely-moving rats evokes a pressor response which is
      mediated primarily by sympathoexcitation. Based on the ability of these
      substances to induce a pressor response via sympathoexcitation and the ability of
      NPY to modify responses evoked by several other neurotransmitters, the present
      study was undertaken to determine if NPY can alter the pressor response evoked by
      subsequent administration of CCh into the PHN. Microinjection of CCh into the PHN
      in six doses ranging from 0.4 to 11 nmol induced a dose-dependent increase in
      mean arterial pressure (MAP) and area under the curve of the change in MAP.
      Administration of 0.23 nmol of NPY into the PHN induced a small but significant
      increase in MAP when compared to the change observed after the microinjection of
      0.9% saline. This NPY-induced increase was blocked by pretreatment with 2.3 nmol
      of the Y receptor antagonist PYX-2. Administration of 0.23 nmol of NPY 60 min
      prior to CCh induced a parallel shift to the left of the dose-response curves for
      CCh resulting in an increase in relative potency for CCh of 6.4 to 6.9 times.
      This NPY-mediated enhancement was prevented by pretreatment with PYX-2 which
      alone did not affect the CCh-induced pressor response. These results show that
      NPY enhances the pressor response evoked by CCh administration into the PHN of
      the conscious rat and that this enhancement is mediated by stimulation of a Y
      receptor.

PMID- 12213303
TI  - Cytochrome c release and caspase activation after traumatic brain injury.
AB  - Experimental traumatic brain injury (TBI) results in a rapid and significant
      necrosis of cortical tissue at the site of injury. In the ensuing hours and days,
      secondary injury exacerbates the primary damage resulting in significant
      neurological dysfunction. The identification of cell death pathways that mediate
      this secondary traumatic injury have not been elucidated, however recent studies
      have implicated a role for apoptosis in the neuropathology of traumatic brain
      injury. The present study utilized a controlled cortical impact model of brain
      injury to assess the involvement of apoptotic pathways: release of cytochrome c
      from mitochondria and the activation of caspase-1- and caspase-3-like proteases
      in the injured cortex at 6, 12 and 24 h post-injury. Collectively, these results
      demonstrate cytochrome c release from mitochondria and its redistribution into
      the cytosol occurs in a time-dependent manner following TBI. The release of
      cytochrome c is accompanied by a time-dependent increase in caspase-3-like
      protease activity with no apparent increase in caspase-1-like activity. However,
      pretreatment with a general caspase inhibitor had no significant effect on the
      amount of cortical damage observed at 7 days post-injury. Our data suggest that
      several pro-apoptotic events occur following TBI, however the translocation of
      cytochrome c itself and/or other events upstream of caspase activation/inhibition
      may be sufficient to induce neuronal cell death.

PMID- 12213304
TI  - Differential effects of urinary bladder distension on high cervical projection
      neurons in primates.
AB  - Projection neurons located in high cervical segments of primates are generally
      excited instead of inhibited by cardiopulmonary spinal inputs, which enter
      thoracic dorsal roots. Thus, high cervical neurons with axons that either ascend
      to the thalamus or descend to thoracolumbar spinal segments can process and
      transmit excitatory cardiac information. The purpose of this study was to
      determine whether the excitatory effects observed to cardiopulmonary afferent
      stimulation are a universal response in high cervical projection neurons to
      spinal visceral inputs. Urinary bladder distension (UBD) was used to stimulate
      visceral afferent inputs that enter lumbosacral dorsal roots. Effects were
      determined on extracellular activity of either spinothalamic tract (STT) neurons
      or descending propriospinal neurons that were recorded in high cervical segments
      of anesthetized monkeys. Results showed that 17/34 STT neurons were inhibited by
      UBD and 3/34 STT neurons were excited. Widespread visceral inputs, therefore, can
      excite high cervical STT neurons but the majority of responsive STT neurons were
      inhibited by UBD. Effects of UBD on high cervical descending propriospinal
      neurons were significantly different from responses in STT neurons. Extracellular
      activity of fewer propriospinal neurons was affected by UBD and responses were
      more variable; 3/26 neurons were inhibited, 5/26 neurons were excited and one
      neuron was excited/inhibited by UBD. These results showed that the generally
      excitatory responses of high cervical projection neurons to cardiopulmonary
      inputs were not duplicated by stimulation of sensory input from the urinary
      bladder. Furthermore, results of this study indicated that effects of sensory
      inputs on spinal neurons might vary depending on axonal projections of the
      neurons examined.

PMID- 12213305
TI  - Ca(2+) stores and capacitative Ca(2+) entry in human neuroblastoma (SH-SY5Y)
      cells expressing a familial Alzheimer's disease presenilin-1 mutation.
AB  - Presenilins are involved in the proteolytic production of Alzheimer's amyloid
      peptides, but are also known to regulate Ca(2+) homeostasis in various cells
      types. In the present study, we examined intracellular Ca(2+) stores coupled to
      muscarinic receptors and capacitative Ca(2+) entry (CCE) in the human
      neuroblastoma SH-SY5Y cell line, and how these were modulated by over-expression
      of either wild-type presenilin 1 (PS1wt) or a mutant form of presenilin 1 (PS1
      deltaE9) which predisposes to early-onset Alzheimer's disease. Ca(2+) stores
      discharged by application of 100 microM muscarine (in Ca(2+)-free perfusate) in
      PS1wt and PS1 DeltaE9 cells were significantly larger than those in control
      cells, as determined using Fura-2 microfluorimetry. Subsequent CCE, observed in
      the absence of muscarine when Ca(2+) was re-admitted to the perfusate, was
      unaffected in PS1wt cells, but significantly suppressed in PS1 deltaE9 cells.
      However, when Ca(2+) stores were fully depleted with thapsigargin, CCE was
      similar in all three cell groups. Western blots confirmed increased levels of PS1
      in the transfected cells, but also demonstrated that the proportion of intact PS1
      in the PS1 deltaE9 cells was far greater than in the other two cell groups. This
      study represents the first report of modulation of both Ca(2+) stores and CCE in
      a human, neurone-derived cell line, and indicates a distinct effect of the PS1
      mutation deltaE9 over wild-type PS1.

PMID- 12213306
TI  - Chondroitin sulfate proteoglycan phosphacan/RPTPbeta in the hypothalamic
      magnocellular nuclei.
AB  - The hypothalamo-neurohypophysial system synthesizes and releases arginine
      vasopressin (AVP) and oxytocin (OXT) with physiological stimulation. In the
      present study, we investigated localization of a chondroitin sulfate proteoglycan
      (CSPG), phosphacan/RPTPbeta, in the supraoptic nucleus (SON) and paraventricular
      nucleus (PVN) of adult rats at both the light and electron microscopic levels.
      Immunohistochemical analyses demonstrated stronger phosphacan/RPTPbeta
      immunoreactivity within the SON and PVN compared with adjacent hypothalamic
      areas. Double labeling experiments showed phosphacan/RPTPbeta immunoreactivity
      constituting punctate networks to surround the somata and dendrites of AVP- and
      OXT-secreting magnocellular neurons. Electron microscopic examination further
      revealed strong phosphacan/RPTPbeta immunoreactivity at extracellular membrane
      surface of some axons, somata, and dendrites of the SON, but not of synaptic
      junctions. Interestingly, phosphacan/RPTPbeta immunoreactivity was also observed
      at extracellular surface membrane between astrocytic processes and neurons rather
      than between magnocellular neurons. The present results indicate the high
      expression of the CSPG, phosphacan/RPTPbeta at the extracellular space in the
      hypothalamic AVP- and OXT-secreting magnocellular neurons.

PMID- 12213307
TI  - Differential release of corticotropin-releasing hormone (CRH) in the amygdala
      during different types of stressors.
AB  - The purpose of this study was to determine if differences exist between the
      effects of acute treadmill running and restraint stress on corticotropin
      releasing hormone (CRH) release within the amygdala of rats. Extracellular CRH
      immunoreactivity (CRH-IR) was measured in microdialysate collected from the
      central nucleus of the amygdala (CeA) during exposure to an inactivated treadmill
      (TC), during 1 h treadmill running to exhaustion (RUN), and 1 h restraint (RES).
      Extracellular CRH-IR increased from control levels during the first 20-min period
      for TC, RUN, and RES, with the largest increase during RES. During the second 20
      min period, only RES maintained levels higher than control values. CRH release
      was higher than control during the third 20-min period of RES and RUN. A second
      experiment consisted of four groups of either cage controls (CC), TC, RUN, or
      RES. Immediately following the 60-min treatment, brains were removed and trunk
      blood collected for analysis of tissue CRH-IR and plasma corticosterone. While
      amygdala tissue CRH-IR was not different in the CC, TC and RUN rats, these groups
      had significantly lower levels than the RES animals. Hypothalamic tissue CRH-IR
      was not different between the CC and TC rats, but the levels were significantly
      higher in the RES and RUN rats than in the two control groups. Plasma
      corticosterone levels were elevated only in RES and RUN rats. Results from tissue
      analysis indicate that increased tissue CRH-IR in the amygdala and hypothalamus
      can be elicited by RES, while only the hypothalamus shows an increase following
      RUN. Further, extracellular CRH release in the CeA is increased throughout the
      period of RES, when rats are placed on the treadmill, and when the animals are
      approaching physical exhaustion. No increase is observed during the running
      period between placement on the treadmill and intense exertion. Overall, the data
      suggest that amygdala CRH release is regulated differently during treadmill
      running and restraint.

PMID- 12213308
TI  - Changes in synaptic plasticity in the rat hippocampo-medial prefrontal cortex
      pathway induced by repeated treatments with fluvoxamine.
AB  - The present studies were conducted to examine the effects of single and repeated
      treatments with fluvoxamine, which is a selective serotonin reuptake inhibitor
      (SSRI), on the synaptic efficacy and synaptic plasticity in the rat hippocampo
      medial prefrontal cortex (mPFC) pathway in vivo. It has been reported that the
      projections arising from the hippocampal structures to the mPFC are involved in
      the execution of higher cognitive functions in rats. The evoked potentials were
      recorded in the mPFC by stimulation of the CA1/subicular region of the ventral
      hippocampus in halothane-anesthetized rats. Single administration of fluvoxamine
      (10 and 30 mg/kg, i.p.) enhanced synaptic efficacy in the hippocampo-mPFC pathway
      in a dose-dependent manner. Although repeated treatments with fluvoxamine (30
      mg/kg, i.p. after 30 mg/kg/dayx21 days, p.o.) caused an enhancement of synaptic
      efficacy, there was no significant difference between single and repeated
      treatments. The input/output characteristics showed hypersensitivity to
      stimulation intensity in the group with repeated fluvoxamine treatments. The
      establishment of long-term potentiation (LTP) in the hippocampo-mPFC pathway
      after a single administration of fluvoxamine was not different from that in the
      saline-injected group. On the other hand, the hippocampo-mPFC LTP was
      significantly augmented by repeated treatments with fluvoxamine when compared to
      a single treatment. These findings suggest that the serotonergic system could
      modulate the synaptic plasticity at hippocampal-mPFC synapses. The present study,
      furthermore, suggests that the enhancement of LTP in the hippocampo-mPFC pathway
      produced by repeated treatments with fluvoxamine may be implicated in the SSRI
      induced therapeutic effect on psychiatric disorders.

PMID- 12213309
TI  - Leptin regulates interleukin-1beta expression in the brain via the STAT3
      independent mechanisms.
AB  - Leptin is known to be an important circulating signal for regulation of food
      intake and body weight. These effects were suggested to be mediated through the
      hypothalamic center via the Ob-Rb receptor (long isoform of leptin receptor).
      Although short isoforms of leptin receptor exist in many regions of the brain,
      there has been little in vivo functional study of these areas such as for
      leptin's target site. We report here that peripherally applied leptin increased
      interleukin (IL)-1beta transcripts in many regions of the brain such as the
      hypothalamus, the hippocampus, the cortex, the cerebellum and the brainstem.
      Although leptin did not induce STAT3 activation or suppressor of cytokine
      signaling3 (SOCS3) expression in the hypothalamus of the db/db mice, which lack a
      functional Ob-Rb receptor, leptin increased the IL-1beta levels to similar
      extents as normal mice. Therefore, a novel function of leptin is suggested as the
      induction of IL-1beta expression in many regions of the brain via STAT3
      independent mechanisms.

PMID- 12213310
TI  - Fluctuation of serum NO(x) concentration at stroke onset in a rat spontaneous
      stroke model (M-SHRSP). Peroxynitrite formation in brain lesions.
AB  - Malignant stroke-prone spontaneously hypertensive rats (M-SHRSP) develop
      hypertension and stroke at earlier ages than do nonmalignant SHRSP. Our previous
      findings suggested that reactive oxygen species were involved in the development
      of stroke in this strain. Nitric oxide (NO) which is more released at ischemia,
      might play a crucial role in stroke development by producing peroxynitrite, a
      neurotoxic substance. This study investigated whether the development of
      cerebrovascular lesion in M-SHRSP could be assessed by the fluctuation of serum
      NO(x) concentration, and whether peroxynitrite is associated with brain damage.
      Serum NO(x) levels were examined using an automated NO detector. Stroke-onset was
      temporally assessed according to a known method: changes in body weight, water
      intake, and neurologic symptoms. Cerebral lesions were confirmed by magnetic
      resonance imaging (MRI), and Evans blue extravasation at autopsy. MRI taken just
      after estimated stroke onset disclosed brain lesions. The baseline serum NO(x)
      level remained at 15-18 micromol/l, but the level gradually increased prior to
      stroke, and significantly at stroke onset. A marked rise in serum NO(x) occurred
      subsequently at poststroke. Immunohistochemical staining of nitrotyrosine, a
      peroxynitrite marker, was detected around vessels, neuronal cells and parenchyma
      in cerebral lesions. Stroke occurred in 50% of male M-SHRSP at 80 days of age. In
      conclusion, this study provides the first evidence for fluctuation of serum NO(x)
      at the onset of spontaneous stroke accompanying the appearance of peroxynitrite
      in brain lesions. Monitoring serum NO(x) would serve to assess the development of
      brain lesions at least in spontaneous stroke model.

PMID- 12213311
TI  - Cyclic AMP-mediated modulation of epileptiform afterdischarge generation in rat
      hippocampal slices.
AB  - This study assessed the effects of drugs which manipulate the cAMP system on
      afterdischarges (ADs) induced in the CA1 region of rat hippocampal slices. The
      adenylate cyclase activator forskolin (50 microM) and the phosphodiesterase
      inhibitor rolipram (0.1 and 1 microM) enhanced AD generation. These effects were
      reversed by the cAMP-dependent protein kinase inhibitors H-89 (5 microM) and Rp
      cAMPS (100 microM). These findings suggest that AD generation can be modulated
      through cAMP generation and the subsequent activation of the cAMP-dependent
      protein kinase.

PMID- 12213312
TI  - Huperzine A attenuates cognitive deficits and brain injury in neonatal rats after
      hypoxia-ischemia.
AB  - The protective effects of huperzine A, a novel acetylcholinesterase inhibitor, on
      hypoxic-ischemic (HI) brain injury were investigated in neonatal rats. A
      unilateral HI brain injury was produced by the ligation of left common carotid
      artery followed by 1 h hypoxia with 7.7% oxygen in 7-day-old rat pups. After 5
      weeks, HI brain injury in rat pups resulted in working memory impairments shown
      by increased escape latency in a water maze and reduced time spent in the target
      quadrant. The combination of common carotid artery ligation and exposure to a
      hypoxic environment caused the damage in the striatum, cortex, and hippocampus in
      the ipsilateral hemisphere, and the neuronal loss in the CA1 region. Huperzine A
      was administrated daily at the dose of 0.05 or 0.1 mg/kg i.p. for 5 weeks after
      HI injury. The significant protection against HI injury on behavior and
      neuropathology was produced by huperzine A at the dose of 0.1 mg/kg. These
      findings suggest that huperzine A might be beneficial in the treatment of hypoxic
      ischemic encephalopathy in neonates.

PMID- 12213313
TI  - The progression of neuronal, myelin, astrocytic, and immunological changes in the
      rat brain following exposure to aurothioglucose.
AB  - Aurothioglucose (ATG) is presently employed both by clinicians in the treatment
      of advanced rheumatoid arthritis and by neuroscience researchers to generate
      lesions around the circumventricular organs (CVOs) of rodent brains, resulting in
      obese animals. Although the existence of such lesions is well documented, there
      is relatively little information concerning the changes over time of the
      different cell types in the regions surrounding the CVOs. To address this
      question, specific markers allowing identification of four distinct cellular
      populations were used to characterize respective changes over time. Generally,
      regions adjacent to the CVOs were more vulnerable than the CVOs themselves, while
      more caudal structures were more frequently lesioned than more anterior CVO
      regions. Vascular and glial cells appeared to be the initial targets of ATG,
      while neuronal cell death occurred subsequent to the inflammatory response. The
      results of this study help resolve the mechanism of ATG toxicity as reflected by
      a cascade of pathologies that is consistent with disparate cell types exhibiting
      specific changes at specific times.

PMID- 12213314
TI  - Cortical and spinal motor excitability during the premovement EMG silent period
      prior to rapid voluntary movement in humans.
AB  - (1) To delineate the cortical and spinal excitability during the pre-movement
      silent period (PMSP), the motor-evoked potentials (MEPs) and H-reflexes were
      measured for 0-150 ms prior to rapid voluntary movements of 11 healthy subjects.
      The appearance of PMSP was judged from the electromyogram of the agonist muscle
      at each rapid movement and the differences of MEPs or H-reflex between the
      movement which PMSP appeared (PMSP MEPs or PMSP H-reflex) and the movement which
      did not appear (non-PMSP MEPs or non-PMSP H-reflex) were compared. (2) The mean
      amplitudes of the PMSP MEPs in the flexor carpi radialis were significantly
      smaller than the non-PMSP MEPs, whereas the mean amplitude of the PMSP H-reflex
      was not significantly different from the non-PMSP H-reflex. (3) In the soleus
      muscle, the change in MEPs and H-reflexes was examined at three periods for 0-150
      ms before the rapid movements. The mean amplitudes of PMSP MEPs for the -150- to 
      100-ms period and for the -50- to -5-ms period were significantly smaller than
      those of non-PMSP MEPs. On the other hand, the differences of the mean amplitudes
      between PMSP H-reflex and non-PMSP H-reflex at the three periods were not
      significant. (4) These findings suggested that the cortical sensitivity to the
      TMS was decreased during PMSP though the spinal inhibitory mechanisms assess by H
      reflex was not altered during the PMSP and that the EMG pause of the PMSP
      originates not at the spinal level but at the cortical level. The data support
      the hypothesis that PMSP is preprogrammed in the preparation and initiation
      process of the voluntary movements aimed at reinforcement of the performance of
      the subsequent ballistic movements.

PMID- 12213315
TI  - Mesencephalic substrate of reward: possible role for lateral pontine tegmental
      cells.
AB  - The present study was aimed at determining whether cells located in the lateral
      pontine tegmentum could constitute part of the neural circuitry that mediates the
      rewarding effect of mesencephalic electrical brain stimulation. Single action
      potentials were recorded from lateral pontine tegmental cells in urethane
      anesthetized rats following antidromic activation from the ventral tegmental area
      and/or posterior mesencephalon. A total of 445 cells were recorded in 13 animals
      and of these, 44 were antidromically driven from the ventral tegmental area (n=13
      ipsi-, n=5 contralateral), the posterior mesencephalon (n=8 ipsi-, n=5 midline),
      or from both sites (n=13). The occurrence of collision between ortho- and
      antidromic action potentials triggered by concurrent stimulation of both sites is
      consistent with psychophysical data obtained previously in behaving animals, and
      likewise suggests that the two sites are linked by uninterrupted axons. In five
      of the cells that were driven from both sites, the inter-electrode conduction
      time exceeded the difference in latencies, suggesting that stimulation of the
      ventral tegmental area and posterior mesencephalon triggered action potentials in
      different axonal branches of the same cell. Estimates of the end of the absolute
      refractory period ranged from 0.44 to 1.6 ms (ventral tegmental area) and from
      0.3 to 2.0 ms (posterior mesencephalon), times that overlap with behaviorally
      derived estimates for mesencephalic reward-relevant neurons. These results
      suggest that cells originating in the lateral pontine tegmentum might constitute
      part of the directly-stimulated substrate responsible for the rewarding effect of
      mesencephalic electrical brain stimulation.

PMID- 12213316
TI  - Group IB secretory phospholipase A(2)induces cell death in the cultured cortical
      neurons: a possible involvement of its binding sites.
AB  - In primary cultures of rat cortical neurons, group IB secretory phospholipase
      A(2) (sPLA(2)-IB) induced cell death. In rat cortical membranes, there were high
      affinity binding sites of [125I]sPLA(2)-IB. The high-affinity binding sites were
      decreased by sPLA(2)-IB and anti-sPLA(2) receptor immunoglobulin G (anti-sPLA(2)R
      IgG). Furthermore, anti-sPLA(2)R IgG caused neuronal cell death in a
      concentration-dependent manner. The present study suggests that sPLA(2)-IB
      induces neuronal cell death via its high-affinity binding sites.

PMID- 12213317
TI  - 30 mm regeneration of rat sciatic nerve along collagen filaments.
AB  - This paper describes 30 mm regeneration of peripheral nerve axons along collagen
      filaments; 31-mm-long collagen filaments or collagen tube were grafted to bridge
      a 30-mm defect of rat sciatic nerve. The mean number and the diameter of
      regenerated myelinated axons were 330+/-227 and 2.7+/-0.9 microm at the distal
      end of the collagen-filaments 12 weeks postoperatively; while at the distal end
      of the tube no axon was found.

PMID- 12213318
TI  - GHRH and IL1beta increase cytoplasmic Ca(2+) levels in cultured hypothalamic
      GABAergic neurons.
AB  - GHRH and IL1beta regulate sleep via the hypothalamus. However, actions of these
      substances on neurons are poorly understood. In this study, we found both GHRH
      (100 nM) and IL1beta (1.2 pM) acutely increased cytosolic Ca(2+) in 7.6 and 4.0%
      of cultured hypothalamic neurons tested, respectively, and 1.2% of neurons
      responded to both. The neurons that responded were mostly GABAergic (96, 81, and
      100% for GHRH, IL1beta, and dual-responsive neurons, respectively).

PMID- 12213319
TI  - Optical imaging of glycinergic inhibition in the vestibular and cochlear nuclei.
AB  - Using multiple-site optical recording techniques, the spatiotemporal activity was
      observed in both the cochlear and vestibular nucleus in newborn mice. The optical
      responses were obviously enhanced by bath-applied strychnine. A quantitative
      analysis showed higher enhancements to occur in the cochlear nucleus than in the
      vestibular nucleus. Optical imaging enables us to visualize the spatiotemporal
      extent of the inhibitory receptive field after the application of strychnine.

PMID- 12213320
TI  - Brain-derived neurotrophic factor expression is increased in the rat amygdala,
      piriform cortex and hypothalamus following repeated amphetamine administration.
AB  - The amygdala plays an important role in the regulation of motivational states,
      especially those associated with addiction. The amygdala also expresses high
      levels of brain-derived neurotrophic factor (BDNF), an activity-dependent
      neurotrophin that can influence the reinforcing and locomotor activating
      properties of psychostimulants. In the present study, we examined the effects of
      acute and repeated amphetamine administration on the expression and production of
      this factor in the forebrain of rats. Animals given a single, acute injection (5
      mg/kg, i.p.) of D-amphetamine developed hyperactivity followed by stereotypical
      behavior but showed no change in the basal expression of BDNF mRNA or its
      immunocytochemical profile in any region except the piriform cortex. Repeated
      injections (5 days) of 5 mg/kg amphetamine were accompanied by an enhanced onset
      of stereotypical behavior and elevated BDNF mRNA in the basolateral amygdala,
      rostral piriform cortex and paraventricular nucleus of the hypothalamus. Repeated
      treatment also increased BDNF immunoreactivity in perikarya of these same
      regions. In addition, increased BDNF immunoreactivity was found in fibers of many
      projection targets of the basolateral amygdala--the central extended amygdala,
      olfactory tubercle, medial nucleus accumbens, and in small zones resembling
      striosomes in the dorsal medial striatum. These results suggest that the
      upregulation of BDNF expression and protein in the basolateral nucleus of the
      amygdala and its targets could be an important part of the neuroadaptive response
      to psychostimulants.

PMID- 12213321
TI  - CS1, a novel member of the CD2 family, is homophilic and regulates NK cell
      function.
AB  - CS1 is a novel member of the CD2 subset of immunoglobulin superfamily (IgSF)
      expressed on NK, T and stimulated B cells. The cytoplasmic domain of CS1 contains
      immunoreceptor tyrosine-based switch motif (ITSM) which is present in 2B4, SLAM
      and CD84. The signaling adaptor molecule SAP/SH2D1A, the defective gene in X
      linked lymphoproliferative disease (XLPD), binds to ITSM and regulates immune
      cell function. However, recent studies indicate that CS1 may be regulated by a
      SAP-independent mechanism. In this study, we have examined the ligand specificity
      of CS1 and the effect of CS1 interaction with its ligand on the cytolytic
      activity of YT, a human NK cell line. Recombinant fusion protein, CS1-Ig,
      containing the CS1 extracellular domain and Fc portion of the human IgG bound
      cells transfected with CS1. CS1-Ig did not show any binding to cells expressing
      other members of the CD2 family. The cytolytic activity of YT was enhanced in
      presence of soluble CS1-Ig fusion protein. These results demonstrate that CS1 is
      a self-ligand and homophilic interaction of CS1 regulates NK cell cytolytic
      activity.

PMID- 12213322
TI  - Characterization of an upstream open reading frame in the 5' untranslated region
      of PR-39, a cathelicidin antimicrobial peptide.
AB  - Cathelicidins are antimicrobial peptides present in humans, and laboratory and
      domestic animals. These peptides are essential components of innate and acquired
      immune responses; however, little is known about cathelicidin gene regulation. To
      investigate the regulatory mechanisms of cathelicidin gene expression, we
      characterized the promoter of the PR-39 gene, a multifunctional cathelicidin.
      Deletion analysis identified a negative regulatory element in the 5'-flanking
      region of the gene located in the sequence from nt (nucleotide(s)) -69 to -63.
      Site-directed mutagenesis indicated that ATG and its vicinity nucleotides are
      critical for the repressive activity of this region. A primer extension assay
      identified a transcription start site upstream from the negative repressor ATG
      and 76 nt upstream from the major open reading frame (ORF). RT-PCR and 3'-RACE
      further demonstrated that cDNA of PR-39 and the cathelicidin porcine myeloid
      antimicrobal peptide (PMAP)-23, which share prepro sequence identity, start from
      nt -79. Sequencing of this region showed that the 5' untranslated region (UTR) of
      the gene contains an upstream translation start site and an upstream ORF that
      functions as a repressor of the PR-39 gene. These findings indicate extensive
      regulation of the PR-39 gene and suggest a mechanism for the tissue-specific and
      age-dependent repression of this cathelicidin gene.

PMID- 12213323
TI  - Single-chain Fv fragment lacks carrier specificity of the native antibody.
AB  - A single-chain antibody fragment (scFv) was constructed from a hybridoma antibody
      that binds to phosphorylcholine (PC) only when this hapten is presented in the
      form of the immunizing antigen (derived from Trichinella) but not when it is
      presented on other carriers (as found, for example, in pneumococcal capsules).
      The scFv derivative was found to lack this carrier specificity as it bound
      indiscriminately, but specifically, to the various PC-associated antigens, and
      exhibits a two-fold lower affinity (3.5x10(5)M(-1)) for nitrophenyl-PC than the
      native antibody. The findings suggest that the scFv combining site is different
      in fine structure from that of the native antibody.

PMID- 12213324
TI  - Synergistic interaction of MEF2D and Sp1 in activation of the CD14 promoter.
AB  - The expression of CD14, a monocyte receptor for the bacterial lipopolysaccharide
      (LPS), is upregulated during monocytic cell differentiation. Although a Sp1 site
      at -110bp of the CD14 promoter was shown to be critical for activation of the
      promoter during the differentiation, how the Sp1 site is regulated has not been
      well understood. We have recently reported that expression of MEF2D protein
      increases during the differentiation of HL60 promyeloid cells to monocyte and
      that the upregulation of the protein is required for CD14 expression during the
      differentiation [Mol. Immunol. 36 (1999) 1209]. However, there is no obvious MEF2
      binding site in the critical region of the CD14 promoter. In this study, which
      aimed to determine the regulatory role of MEF2D in monocytic cell
      differentiation, MEF2D was found to form a complex with Sp1 in U937 promyeloid
      cells. Transient transfection experiments showed that co-expression of MEF2D and
      Sp1 synergistically activated the CD14 promoter. The results support a model in
      which increased MEF2D protein during monocytic cell differentiation activates the
      CD14 promoter through interaction with Sp1.

PMID- 12213325
TI  - Two V(H)5 family genes expressed by human peripheral B cells display differential
      mutational frequencies in the V(H) region.
AB  - The heavy chain variable segment gene (V(H))5 family, one of the seven
      immunoglobulin (Ig) V(H) families, contains two functional genes, VH251 and VH32.
      To investigate functional differences between these V(H)5 family genes, V(H)
      segments expressed by human peripheral B cells were sequenced and analyzed. One
      hundred fifty-three sequences with unique V(H)DJ(H) recombinations were obtained
      from 17 adults. The mutational frequency of VH32 derived sequences (6.4%) was
      higher than that of VH251 derived sequences (4.4%), resulting in a significant
      difference (P<0.01). Significant differences in mutational frequencies between
      VH251 and VH32 derived sequences were observed in CDRs and FRs. No significant
      differences were found in CDR3 length distribution, D segment usage, or J(H)
      segment usage between VH251 and VH32 derived sequences. These results suggest
      that mutational frequency is affected, in part, by V(H) gene structure. The
      difference may occur after recombinational events in B cell development.

PMID- 12213326
TI  - Novel characterisation of the gene encoding conglutinin reveals that previously
      characterised promoter corresponds to the CL-43 promoter.
AB  - Conglutinin, a collectin found in bovine serum, is an opsonin that binds to
      glycoconjugates on the surface of microorganisms or on deposited iC3b, and acts
      in concert with phagocytes to establish a first-line of immune defense. We have
      isolated a genomic conglutinin phage clone and found that the 5'-flanking region
      shows 95.8% identity with the sequence previously published, which on the other
      hand shows 99.7% identity with the CL-43 promoter. We conclude that the
      previously published promoter corresponds to the CL-43 promoter and that the
      functional studies performed on it apply to transcription of CL-43. Comparison of
      potential cis-regulatory elements in relation to the functional studies indicates
      that the two genes are regulated by different mechanisms.

PMID- 12213327
TI  - Analysis of the complex genomic structure of Bcl-x and its relationship to Bcl
      x(gamma) expression after CD28-dependent costimulation.
AB  - The Bcl-x(gamma) cytosolic protein is essential for costimulatory activity after
      CD3/CD28 coligation. Here we delineate the Bcl-x(gamma)/Bcl-x genomic
      organization and the molecular mechanism that allows expression. We show that
      exon 4 of the Bcl-x gene encodes the unique C-terminal end of the Bcl-x(gamma)
      molecule while exons 5, 6, 7 and 8 are differentially transcribed to yield three
      alternative Bcl-x(gamma) 3' untranslated regions (UTR). CD28-dependent signals
      may increase levels of Bcl-x(gamma) protein through induction of an alternatively
      spliced Bcl-x(gamma) 3' UTR that contains stem loop structures that stabilize Bcl
      x(gamma) RNA. The ability receptor-induced signals to regulate the splicing
      pattern of the complex Bcl-x gene may allow T-cells to respond appropriately to
      antigenic stimuli.

PMID- 12213328
TI  - Defective CD19-dependent signaling in B-1a and B-1b B lymphocyte subpopulations.
AB  - Peritoneal and pleural cavities in mice and humans contain a unique population of
      B-lymphocytes called B-1 cells that are defective in B cell antigen receptor
      (BCR) signaling but have an increased propensity to produce autoantibodies.
      Several molecules such as Btk, Vav, and CD19 known to be important for BCR
      signaling have been shown to be critical for the development of B-1 cells from
      undefined precursors. Here we demonstrate that B-1 cell unresponsiveness to BCR
      cross-linking is in part due to defective signaling through CD19, a molecule
      known to modulate signaling thresholds in B cells. The defective CD19 signaling
      is manifested in reduced synergy between mIgM and CD19 to stimulate calcium
      mobilization in B-1 cells. BCR induced tyrosine phosphorylation of CD19 was
      transient in B-1 cells while it was prolonged in splenic B-2 cells. In both B-1
      and B-2 cells BCR cross-linking induced a modest increase of CD19 associated Lyn,
      a Src family protein tyrosine kinase (PTK) thought to be important for CD19
      phosphorylation. However, the tyrosine phosphorylated CD19 in B-1 cells binds
      less phosphatidylinositol 3-kinase (PI3-K) compared to B-2 cells. Most
      interestingly, we find that Vav-1 and Vav-2, proteins thought to be critical for
      CD19 signal transduction, are severely reduced in B-1 cells resulting in a
      complete absence of any CD19 associated Vav. Also we showed that both B-1a and B
      1b B cells failed to proliferate in response to BCR cross-linking which in part
      appears to be due to defects in CD19 mediated amplification of BCR induced
      calcium mobilization.

PMID- 12213330
TI  - Variation in the ordered structure of complexes between CD154 and anti-CD154
      monoclonal antibodies.
AB  - The cell surface co-stimulatory protein CD154 (CD40L) is a target for monoclonal
      antibody (mAb) inhibitors of T-cell mediated immune diseases. This protein, like
      most other members of the TNF ligand family, forms homotrimeric complexes on the
      cell surface and in solution, with a three-fold axis of symmetry. We find that
      several different anti-CD154 monoclonal antibodies form distinctive complexes
      with soluble CD154. These soluble complexes have been analyzed using size
      exclusion chromatography, static and dynamic light scattering, and electron
      microscopy and shown to consist of caged structures of various geometries. The
      cell surface complexes have been analyzed by confocal microscopy and, depending
      on the mAb, remain as small, separate complexes or form large aggregates. The
      formation of these complexes in solution is likely to have an impact on measures
      of affinity, while the cell surface complexes could affect binding potency and
      provoke other biological effects.

PMID- 12213329
TI  - Zinc induces exposure of hydrophobic sites in the C-terminal domain of gC1q
      R/p33.
AB  - Endothelial cells and platelets are known to express gC1q-R on their surface. In
      addition to C1q, endothelial cell gC1q-R has been shown to bind high molecular
      weight kininogen (HK) and factor XII (FXII). However, unlike C1q, whose
      interaction with gC1q-R does not require divalent ions, the binding of HK to gC1q
      R is absolutely dependent on the presence of zinc. However, the mechanism by
      which zinc modulates this interaction is not fully understood. To investigate the
      role of zinc, binding studies were done using the hydrophobic dye, bis-ANS. The
      fluorescence intensity of bis-ANS, greatly increases and the emission maximum is
      blue-shifted from 525 to 485nm upon binding to hydrophobic sites on proteins. In
      this report, we show that a blue-shift in emission maximum is also observed when
      bis-ANS binds to gC1q-R in the presence but not in the absence of zinc suggesting
      that zinc induces exposure of hydrophobic sites in the molecule. The binding of
      bis-ANS to gC1q-R is specific, dose-dependent, and reversible. In the presence of
      zinc, this binding is abrogated by monoclonal antibody 74.5.2 directed against
      gC1q-R residues 204-218. This segment of gC1q-R, which corresponds to the beta6
      strand in the crystal structure, has been shown previously to be the binding site
      for HK. A similar trend in zinc-induced gC1q-R binding was also observed using
      the hydrophobic matrix octyl-Sepharose. Taken together, our data suggest that
      zinc can induce the exposure of hydrophobic sites in the C-terminal domain of
      gC1q-R involved in binding to HK/FXII.

PMID- 12213331
TI  - Identification of a novel immunoglobulin delta transcript and comparative
      analysis of the genes encoding IgD in Atlantic salmon and Atlantic halibut.
AB  - Atlantic salmon possesses two parallel Ig heavy chain gene complexes, A and B,
      most probably as a result of ancestral tetraploidy. Consequently, there are two
      distinct IgD heavy chain (delta) subvariants in this species. The Igdelta(B) gene
      was characterised in a previous study. In the present work the Igdelta(A) gene
      was amplified by PCR and sequenced. Both Igdelta genes in salmon have a structure
      like delta1-(delta2-delta3-delta4)(2)-delta5-delta6-delta7-TM1-TM2 and show a
      high degree of sequence identity (approximately 95%). 3'RACE and RT-PCR analyses
      performed in the present study indicate that Igdelta transcripts of membrane type
      are dominating in Atlantic salmon and Atlantic halibut. However, a different
      transcript, originating from the Igdelta(B) gene in salmon, was identified by
      PCR. This RNA fragment is spliced between the regular donor/acceptor sites in
      delta6 and TM2. Cloning and characterisation of cDNA encoding the membrane form
      of halibut IgD revealed an overall Ig domain structure equivalent to that in
      salmon. Corresponding duplications of delta2-delta3-delta4 have now been found in
      three teleost fishes: salmon, halibut and catfish. The tandem duplicated
      fragments are highly similar within each species, while not being especially
      conserved between the species. Thus, the duplicated gene fragments have either
      arisen independently in each species or are subjected to homogenisation by some
      means.

PMID- 12213332
TI  - Influence of the 3D-conformation, glycan component and microheterogeneity on the
      epitope structure of Ole e 1, the major olive allergen. Use of recombinant
      isoforms and specific monoclonal antibodies as immunological tools.
AB  - Ole e 1 is the main allergen of olive pollen, which is a major cause of
      pollinosis in countries of the Mediterranean area. Nine Ole e 1-specific murine
      monoclonal antibodies (mAbs), as well as two Ole e 1-isoforms and two Ole e 1
      like allergens from lilac and privet, all of them obtained in Pichia pastoris by
      recombinant methods, have been used as tools to determine the role of the three
      dimensional (3D)-folding, the glycan component and several point changes of the
      amino acid sequence in the binding of murine IgG mAbs and human IgE to the olive
      allergen. Seven mAb families (F1-F7) were established, two of which (F1 and F2)
      recognize continuous epitopes. The carbohydrate moiety of Ole e 1 was involved in
      the binding to F2 and F4, whereas F3 and F7 were able to bind to all Ole e 1
      variants. The remaining families of IgG murine antibodies exhibited different
      affinities for the antigens assayed in a native or denatured conformation.
      Although the binding of human IgE to Ole e 1 was not affected by heat treatment,
      it was shown to be strongly dependent on the integrity of the disulfide bridges
      and was partially inhibited by F3-F7 IgG antibodies, their individual values
      ranging from 12 to 31% and reaching 53% with their mixture. The IgE from sera of
      olive-allergic patients showed a significant diversity of binding capacity to the
      members of the Ole e 1-like family due to the microheterogeneity of their
      polypeptide sequences, in spite of their highly conserved primary structures.
      Whereas one of the isoforms of Ole e 1 exhibits a highly similar behavior to the
      natural form, being a putative molecule for diagnostic purposes, other ones can
      be considered as hypoallergenic variants of this allergen and, thus, potential
      candidates to be used in immunotherapy.

PMID- 12213333
TI  - A monoclonal antibody against NeuGc-containing gangliosides contains a regulatory
      idiotope involved in the interaction with B and T cells.
AB  - P3 (IgM-kappa) is a monoclonal antibody (mAb) reacting with N-glycolyl neuraminic
      acid (NeuGc)-containing gangliosides and sulfated glycolipids. To explore the
      nature of the idiotope defined by 1E10, we used a phage-displayed random peptide
      library. After three rounds of selection, seven different phagotopes were
      isolated. Noteworthy, all the sequences were found to bear the basic amino acid
      rich motifs KPPR (3) or RRPR/K (4). This recursive selection of basic sequences
      by 1E10 mAb confirmed previous suggestions of the involvement of charged residues
      in the interaction between gamma-type Ab2 and P3 mAb. The binding of 1E10 to
      phage peptides representing each group was completely inhibited by P3 mAb. In
      addition, other Ab2 to P3 were able to recognize these peptides. Thus, phage
      peptides seem to be mimotopes of the idiotope recognized by anti-idiotypic
      antibodies in P3. Phage motifs were represented in the lineal sequence of P3's
      heavy chain H-CDR3 and a 14-mer peptide representing this region was able to
      specifically inhibit 1E10 binding to P3. Previous studies showed that P3's
      idiotype was autoimmunogenic and shared by antibodies with different
      specificities. Now, we demonstrated that P3 mAb is able to activate a network
      cascade involving autologous anti-idiotypic and anti-anti-idiotypic T cells.
      Thus, P3's idiotype fulfill the three criteria previously established to define a
      "regulatory idiotype". Particularly, data presented here revealed the
      immunodominance of the H-CDR3 of this mAb as a T cell epitope. Thus, H-CDR3 is
      simultaneously involved in the interaction of P3 mAb with anti-idiotypic B and T
      cells, behaving as a potential regulatory idiotope.

PMID- 12213334
TI  - Development of new vaccines and diagnostic reagents against tuberculosis.
AB  - Tuberculosis (TB) is a major infectious disease problem with one-third of the
      world population infected, 8 million people developing the active disease and 2
      million dying of TB each year. The attenuated Mycobacterium bovis Bacillus
      Calmette Guerin (BCG) is the only available vaccine against TB. However, the
      trials conducted in different parts of the world have shown that this vaccine doe
      not provide consistent protection against TB. The purified protein derivative
      (PPD) of Mycobacterium tuberculosis is the commonly used reagent for the
      diagnosis of TB. However, PPD lacks specificity because of the presence of
      antigens crossreactive with M. bovis BCG and other mycobacteria. The studies to
      identify M. tuberculosis antigens and epitopes as candidates for new protective
      vaccines and specific diagnostic reagents against TB have led to the
      identification and characterization of several major antigens of M. tuberculosis
      including heat shock proteins (hsp) and secreted antigens present in the culture
      filtrate (CF) of M. tuberculosis. Some of these antigens have shown promise as
      new candidate vaccines (hsp60, Ag85 and ESAT-6, etc.) and specific diagnostic
      reagents (ESAT-6 and CFP10, etc.) for TB. Moreover, in the mouse model of TB,
      vaccination with DNA-hsp60 has immunotheraputic effects and helps in eradication
      of persisters. In addition, identification of proper adjuvant and delivery
      systems has shown the promise to overcome the problem of poor immunogenicity
      associated with subunit and peptide based vaccines. More recently, the comparison
      of the genome sequence of M. tuberculosis with M. bovis BCG and other
      mycobacteria has led to the identification of M. tuberculosis-specific genomic
      regions. Evaluation of these regions for encoding proteins with immunological
      reactivity can lead to the identification of additional antigens of M.
      tuberculosis useful as new vaccines and reagents for specific diagnosis of TB.

PMID- 12213337
TI  - Oligomeric MHC molecules and their homologues: state of the art.
AB  - This special issue of the Journal of Immunological Methods brings together
      articles from some of the leaders in labelling antigen-specific T and NKT cells,
      describing recent technical advances and their impact on the study of immunology.
      Although tetramers, or tetrameric MHC class I/peptide complexes, are the best
      known reagents in the field, various forms of oligomeric complexes are now being
      successfully used to detect antigen-specific T cells, including cytotoxic T
      lymphocytes, MHC class II-restricted CD4+ T cells, and glycolipid-specific T
      cells restricted by CD1 isoforms. The articles presented here detail the breadth
      of the oligomeric structures being used to probe T, NK and NKT cell function, and
      cover both the technical and practical aspects of their use, as well as the new
      biology revealed. In addition to providing a summary of the current state of the
      art, these contributions also provide clear pointers to strategies likely to
      succeed in the future. In this introductory chapter, we summarise the work
      presented in the other articles of this issue, and provide an overarching view of
      this rapidly evolving field. We also provide a summary of the MHC class I
      molecules successfully refolded to date, and provide references to other relevant
      sources of technical information.

PMID- 12213338
TI  - The assessment of antigen-specific CD8+ T cells through the combination of MHC
      class I tetramer and intracellular staining.
AB  - Peptide-bound histocompatibility leukocyte antigen (HLA) class I tetramers enable
      a precise identification of antigen-specific CD8+ T cells using flow cytometry.
      The combination of this technology with intracellular staining techniques opens
      up significantly better ways of studying these cells than previously possible,
      allowing immunologists to look at their life cycle (activation and
      proliferation), manner of death (aging and apoptosis) and effector function
      (cytotoxic potential and cytokine production). In this review, we hope to provide
      an overview of these possibilities, as well as making specific suggestions about
      the use of intracellular staining techniques in the study of antigen-specific T
      cells. Understanding how antigen-specific cells develop and function in different
      circumstances and pathologies will be the key to unravelling the secrets of our
      cellular immune system.

PMID- 12213339
TI  - MHC/peptide tetramer-based studies of T cell function.
AB  - Direct visualization and quantification of antigen-specific T cells using major
      histocompatibility complex (MHC)/peptide tetramer technology offers a powerful
      means to study specific T cell populations of interest. In combination with
      functional assays, this technology has already provided many new insights into
      several long-standing immunological concepts in basic science as well as clinical
      settings.

PMID- 12213340
TI  - In situ tetramer staining.
AB  - The development of MHC tetramer staining has opened the doors to multiple avenues
      of new research [Science 274 (1996) 94]. In this review, we will discuss the
      development and application of in situ MHC tetramer (IST) staining. We describe
      two independently developed IST staining methodologies and discuss current uses,
      limitations, future uses and the interesting biology revealed by the use of IST
      staining.

PMID- 12213341
TI  - The use of chimeric A2K(b) tetramers to monitor HLA A2 immune responses in HLA A2
      transgenic mice.
AB  - HLA A2 (A2) transgenic mice are currently being used to compare different
      vaccination protocols. However, the monitoring of A2 restricted CTL in A2
      transgenic mice have been hampered by poor staining efficiency of mouse CTL by A2
      tetramers. We demonstrate here that chimeric A2 tetramers containing mouse H
      2K(b) (K(b)) alpha3 domain (A2K(b) tetramers) can be used as staining reagents to
      monitor A2 restricted CTL responses in A2 transgenic mice. The increased ability
      of A2K(b) tetramers to stain mouse A2 restricted CTL, as compared with A2
      tetramers, correlated with their higher binding affinity for mouse A2 restricted
      CTL. The use of these novel staining reagents will allow efficient comparison of
      vaccination strategies and rapid identification of novel CTL epitopes in A2
      transgenic mice.

PMID- 12213342
TI  - Tetrameric complexes of HLA-E, HLA-F, and HLA-G.
AB  - HLA-E, HLA-F, and HLA-G are human nonclassical MHC class Ib molecules. To study
      the function and identify potential ligands of these molecules, we constructed
      tetrameric complexes. In this brief review, we discuss the methods used to
      produce such tetramers and the interesting results they provided. HLA-E tetramers
      bound to natural killer (NK) cells and T cells, allowing the identification of
      CD94/NKG2 molecules as receptors for HLA-E. HLA-G tetramers interacted with
      immunoglobulin-like transcript-2 (ILT2) and ILT4 receptors, aiding the
      understanding of HLA-G function during pregnancy. Tetrameric complexes of HLA-F
      also bound to ILT2 and ILT4.

PMID- 12213343
TI  - Labeling antigen-specific CD4(+) T cells with class II MHC oligomers.
AB  - Class I MHC-peptide oligomers (MHC tetramers) have become popular reagents for
      the detection and characterization of antigen-specific CD8(+) T cells. Class II
      MHC proteins can be produced by expression in Escherichia coli followed by in
      vitro folding, or by native expression in insect cells; biotin can be introduced
      by site-specific chemical modification of cysteine, or by enzymatic modification
      of a peptide tag; and a variety of fluorescent streptavidin preparations can be
      used for oligomerization. Here we review methodologies for production of
      fluorescent oligomers of soluble class II MHC proteins and discuss their use in
      analysis of antigen-specific CD4(+) T cells. We explore the experimental
      conditions necessary for efficient staining of CD4(+) T cells using oligomers of
      class II MHC proteins, and we establish a standard protocol. Finally, we consider
      complications and challenges associated with these reagents, discuss the
      interpretation of staining results, and suggest future directions for
      investigation, in particular the use of MHC oligomers for the study of T cell
      avidity modulation.

PMID- 12213344
TI  - Use of class II tetramers for identification of CD4+ T cells.
AB  - Multivalent MHC class II molecules containing peptide antigens are useful tools
      for the detection of antigen specific human CD4+ T cells. Tetramers produced by
      exogenous peptide loading onto empty class II molecules are comparable to
      tetramers with peptide tethered to the class II chain covalently, but have many
      practical advantages. Conditions for optimal peptide loading to generate
      tetramers are discussed and optimal conditions of using tetramers for staining T
      cells are examined. As the frequency of antigen specific CD4+ T cells in
      peripheral blood is low, we demonstrate that an in vitro expansion step is
      effective in detecting low frequency T cells. Two new applications with
      tetramers, their uses for mapping T cell epitopes and for the detection of low
      affinity T cells are described. In a clinical setting, potential applications
      include using these reagents for monitoring disease progression during clinical
      intervention.

PMID- 12213345
TI  - Generation and use of alternative multimers of peptide/MHC complexes.
AB  - For many years, the detection of antigen-specific T cells has relied on indirect
      in vitro assays such as cytokine secretion, proliferation or chromium release
      assays. Things have dramatically changed during the past few years, thanks to the
      imagination of several investigators who have developed very elegant strategies
      to produce multivalent peptide/MHC complexes. One of these strategies has been to
      produce peptide-loaded monomeric biotinylated MHC molecules, which could be
      obtained as tetramers upon incubation with tetravalent streptavidin. Although
      this latter approach has been by far the most popular, this review focuses on
      other strategies which have also been successful.

PMID- 12213346
TI  - Probing T cell membrane organization using dimeric MHC-Ig complexes.
AB  - In this report, we review a novel method for probing the membrane organization of
      T cells using dimeric major histocompatibility complexes (MHC), MHC-Ig. MHC-Ig
      complexes are useful reagents for quantitative analysis of binding data since
      their valency is controlled. These complexes can be easily labeled and loaded
      with a variety of peptides. A binding assay using these dimers and quantitative
      analysis of the MHC-Ig dimer-T cell binding curves is described in detail. Using
      this approach, we show that the organization of TCR on activated T cells is
      different from TCR organization on nai;ve T cells. The implications of these
      findings are discussed with regards to current models of T cell recognition. This
      analysis offers insight into how T cell controls their biological range of
      responsiveness. Specifically, these findings reveal the biophysical basis of the
      ability of activated T cells to recognize low amounts of antigen independent of
      costimulation.

PMID- 12213347
TI  - CD1 tetramers: a powerful tool for the analysis of glycolipid-reactive T cells.
AB  - CD1 proteins constitute a third class of antigen-presenting molecules. They bind
      lipids rather than peptides, and the T cells reactive to lipids presented by CD1
      have been implicated in the protection against autoimmune diseases and infectious
      microorganisms and in the immune surveillance for tumors. Thus, the ability to
      identify, purify, and track the response of CD1-reactive cells is of paramount
      importance. Previously existing methods for identifying these T cells were not
      based on TCR specificity, and therefore the data obtained by these methods were
      in some cases difficult to interpret. The recent generation of tetramers of alpha
      galactosyl ceramide (alpha-GalCer) with CD1d has already permitted significant
      insight into the biology of NKT cells. Tetramers constructed from other CD1
      molecules also have been obtained during the previous year. Collectively, these
      new reagents promise to greatly expand knowledge of the functions of lipid
      reactive T cells, with potential use in monitoring the response to lipid-based
      vaccines and other treatments and in the diagnosis of autoimmune diseases.

PMID- 12213348
TI  - Differential regulation of gene expression and insulin-induced activation of
      phosphodiesterase 3B in adipocytes of lean insulin-resistant IRS-1 (-/-) mice.
AB  - Phosphodiesterase (PDE) 3B, a major isoform of PDE in adipocytes, mediates the
      antilipolytic action of insulin. PDE3B gene expression is generally reduced in
      adipocytes of either monogenic or polygenic rodent models of obese, insulin
      resistance. An increased fat cell size, a common feature of obesity, could
      account for this reduction. Insulin receptor substrate-1 (IRS-1) (-/-) mice are
      lean with a reduced fat cell size and have insulin resistance due to a primary
      defect of insulin signaling. To determine whether the regulation of PDE3B gene
      expression is correlated with fat cell size, we examined this gene expression in
      adipose tissues of IRS-1 (-/-) mice. In IRS-1 (-/-) mice, PDE3B mRNA and protein
      levels were increased 1.24- and 1.35-fold those in C57BL/6J control mice,
      respectively. Independently, the fold induction of PDE activity by insulin
      (insulin-induced/basal) was 1.7-fold in control mice, but was reduced to 1.35
      fold in IRS-1 (-/-) mice. Thus, PDE3B gene expression may be inversely correlated
      with a fat cell size, whereas insulin-induced PDE3B activation is mediated
      through IRS-1.

PMID- 12213349
TI  - Effective use of thiazolidinediones for the treatment of glucocorticoid-induced
      diabetes.
AB  - We evaluated the efficacy of a thiazolidinedione in the treatment of diabetes
      induced by glucocorticoids. We examined the effectiveness of troglitazone in
      seven patients with long-standing steroid-induced diabetes. Five of the seven
      subjects were treated with insulin alone, one was treated with both insulin and
      oral therapy and one was treated with oral therapy alone. The mean insulin dose
      in six of the seven subjects was 0.66+/-0.09 units/kg per day. Diabetes status
      was assessed by measuring serum fructosamine, HgbA1c, oral glucose and meal
      tolerance tests (OGTT and MTT) at baseline and after treatment for 5-8 weeks with
      troglitazone 400 mg/day. Troglitazone caused a significant decrease in
      fructosamine (274+/-32 vs. 217+/-22 mmol/l; P<0.01) and HgbA1C (7.8+/-0.4 vs.
      7.2+/-0.4%; P<0.01) as well as decrements in the areas under the OGTT 2,308+/-156
      vs. 1,937+/-127 mmol/l; P<0.05) and MTT glucose curves (4694+/-449 vs. 4057+/-437
      mmol/l; P<0.05). In addition, the area under the insulin curve for the oral
      glucose tolerance test showed a significant increase from 27,438+/-4,488 to
      41,946+/-6,048 pmol/l (P<0.05). Total and LDL cholesterol were also significantly
      decreased (6.4+/-0.9 vs. 5.0+/-0.6 mmol/l and 3.8+/-0.7 vs. 2.7+/-0.4 mmol/l,
      respectively, P<0.05). Fasting leptin values decreased by 23% despite an increase
      in body weight. Troglitazone is effective in the treatment of glucocorticoid
      induced diabetes as manifested by lower measures of glycemia, HgbA1c, and post
      prandial glucose values, while the doses of other diabetes medications remained
      unchanged or were reduced. The insulin-sensitizing drug also produced a marked
      increase in endogenous insulin secretion in response to glucose, lower total and
      LDL cholesterol, and decreased fasting leptin despite weight gain.
      Thiazolidinediones may improve diabetes-related parameters by antagonizing
      pathways of glucocorticoid-induced insulin resistance and by reversing adverse
      effects of glucocorticoids on beta cell function.

PMID- 12213350
TI  - High prevalence of diabetes in patients with pancreatic cancer in central
      Anatolia, Turkey.
AB  - Tumor-induced pancreatic damage or insulin resistance may be responsible for
      diabetes in pancreatic cancer (PC) patients, but the exact cause of association
      remains controversial. In this study, we aimed to investigate the prevalence of
      diabetes in patients with PC in central Anatolia, Turkey, and to evaluate whether
      diabetes is caused by PC. A total of 40 patients with primary PC were enrolled in
      the study. 13 (32.5%) of the patients had diabetes before PC diagnosis. Oral
      glucose tolerance test was performed in the remaining 27 patients. The period
      between the diagnosis of diabetes and detection of PC was less than 1 year in
      seven (17.5%) patients who had previous diabetes. Recent-onset diabetes and
      impaired glucose tolerance were detected in 13 (32.5%) and two (5%) of the PC
      patients, respectively. The prevalence of recent-onset and shortly-before
      diagnosed diabetes has been found very high (50%) in our patients with PC.
      Interestingly, we determined higher levels of insulin and C-peptide in PC
      patients having abnormal glucose tolerance than patients having normal glucose
      tolerance. In conclusion, as it has been reported in other population, we
      determined high prevalence of diabetes in PC patients in central Anatolia. High
      insulin and C-peptide level indicate that different mechanisms such as insulin
      resistance may be responsible for abnormal glucose tolerance in PC patients other
      than the tumor caused insulin deficiency.

PMID- 12213351
TI  - Daily walking reduces visceral adipose tissue areas and improves insulin
      resistance in Japanese obese subjects.
AB  - OBJECTIVE: It is known that the accumulation of abdominal fat is one of the risk
      factors for atherosclerosis. Although exercise is commonly prescribed to reduce
      body weight, the efficacy of low intensity exercise for the reduction of
      abdominal visceral adipose tissue remains to be investigated. RESEARCH DESIGN AND
      METHODS: Thirty one obese Japanese males (body mass index (BMI) > or = 25)
      ranging in age from 32 to 59, participated in a 1-year follow up study and they
      were instructed to have a modest increase in daily activity and record their
      daily walking. Before and after exercise prescription, body composition, blood
      pressure, physical fitness i.e. aerobic exercise level, muscle strength and
      flexibility were recorded. Insulin resistance was evaluated using a homeostasis
      model assessment, the HOMA index. RESULTS: HOMA index, parameters of body
      composition, blood pressure, triglyceride and HDL cholesterol were significantly
      improved. The aerobic exercise level, leg strength, weight-bearing index (leg
      strength/body weight) and the steps taken per day were significantly increased.
      By stepwise multiple regression analysis, Delta visceral adipose tissue area was
      the major determinant for Delta HOMA index. (Delta HOMA index=-0.386+0.016 Delta
      visceral adipose tissue area, r2=0.267, P<0.01). Exercise capacity and calorie
      intake were not significantly related to Delta visceral adipose tissue area,
      while Delta steps per day was significantly correlated with Delta visceral
      adipose tissue area (Delta visceral adipose tissue area=-21.363-0.004 Delta steps
      per day, r2=0.184, P=0.0326). CONCLUSIONS: Taken together, intra-abdominal
      visceral adipose tissue is critically involved in insulin resistance and daily
      walking rather than improvement of exercise capacity correlated with the
      reduction of visceral adipose tissue in obese Japanese males.

PMID- 12213352
TI  - Association between plasma oxidized low-density lipoprotein and diabetic
      nephropathy.
AB  - To investigate the association of oxidized low-density lipoprotein (ox-LDL) with
      the development of diabetic nephropathy, plasma levels of ox-LDL were measured in
      70 patients with type 2 diabetes mellitus. A sandwich enzyme-linked
      immunoadsorbent assay (ELISA) using the mouse monoclonal antibody FOH1a/DLH3,
      which specifically recognizes oxidized phosphatidylcholine, and a horseradish
      peroxidase (HRP)-labeled goat anti-human apolipoprotein B IgG was used to measure
      ox-LDL levels. The mean age of the patients was 57.0+/-1 3.4 years, and the mean
      duration of diabetes was 13.4+/-8.5 years. Plasma ox-LDL levels were similar in
      patients with normoalbuminuria (13.7+/-3.9 U/ml), patients with microalbuminuria
      (12.8+/-3.9 U/ml), and normal controls (12.5+/-4.2 U/ml). However, the plasma ox
      LDL level in patients with macroalbuminuria (16.8+/-7.5 U/ml) was significantly
      higher than those in the other groups (P<0.05). Hemoglobin A1c (HbA1c) levels
      were similar in diabetic patients with normoalbuminuria (8.2+/-2.2%),
      microalbuminuria (7.8+/-1.3%), or macroalbuminuria (7.2+/-1.4%). There was no
      significant correlation between the ox-LDL level and the HbA1c level. The
      significantly elevated plasma ox-LDL levels in patients with macroalbuminuria
      suggest that ox-LDL may play an important role in the progression of diabetic
      nephropathy.

PMID- 12213353
TI  - Insulin lispro therapy in pregnancies complicated by type 1 diabetes mellitus.
AB  - OBJECTIVE: To compare the efficacy and safety of preprandial administration of
      rapid-acting lispro analogue with regular short-acting insulin to pregnant women
      with type 1 diabetes. STUDY DESIGN: Open randomised multicentre study. Women were
      treated with multiple insulin injections aiming at normoglycaemia. Blood glucose
      was determined six times daily, HbA(1c) every 4 weeks. Diurnal profiles of blood
      glucose were analysed at gestational week 14 and during the study period at weeks
      21, 28 and 34. PARTICIPANTS: 33 pregnant women with type 1 DM were randomised to
      treatment with lispro insulin (n=16) or regular insulin (n=17). RESULTS: Blood
      glucose was significantly lower (P<0.01) after breakfast in the lispro group,
      while there were no significant group differences in glycemic control during the
      rest of the day. Severe hypoglycaemia occurred in two patients in the regular
      group but biochemical hypoglycaemia (blood glucose <3.0 mmol/l) was more frequent
      in the lispro than in the regular group (5.5 vs. 3.9%, respectively). HbA(1c)
      values at inclusion were 6.5 and 6.6% in the lispro and regular group
      respectively. HbA(1c) values declined during the study period and were similar in
      both groups. There was no perinatal mortality. Complications during pregnancy,
      route of delivery and foetal outcome did not differ between the groups.
      Retinopathy progressed in both groups, one patient in the regular group developed
      proliferative retinopathy. CONCLUSION: The results suggest that it is possible to
      achieve at least as adequate glycemic control with lispro as with regular insulin
      therapy in type 1 diabetic pregnancies.

PMID- 12213354
TI  - Sarpogrelate hydrochloride, a serotonin2A receptor antagonist, reduces
      albuminuria in diabetic patients with early-stage diabetic nephropathy.
AB  - We have recently demonstrated that serotonin (5-HT) increases the production of
      type 4 collagen by cultured human mesangial cells. Here we examined the clinical
      effects of a 5-HT(A2) receptor antagonist whether it would prevent the
      development or progression of diabetic nephropathy. We compared the levels of 5
      hydroxyindole-3-acetic acid (5-HIAA), the major metabolite of 5-HT, in 24-h urine
      samples of patients with type 2 diabetes (n=110) and normal subjects (n=40). We
      then investigated the effects of 24-month treatment with sarpogrelate
      hydrochloride, a 5-HT(A2) receptor antagonist, on urinary albumin level in 10
      type 2 diabetics with microalbuminuria, compared with not treated control group.
      Urinary 5-HIAA in diabetic patients was significantly higher (3.44+/-1.43 mg/day)
      than in normal subjects (1.62+/-0.50 mg/day, P<0.001), and correlated
      significantly with hemoglobin A1c (r=0.56, P<0.001) and with fasting blood
      glucose (r=0.37, P<0.001). Sarpogrelate significantly reduced urinary albumin
      excretion level within 3 months of commencement of treatment (24.3+/-8.58 mg/g
      Cr, P<0.05), which was persistently seen during the treatment, while no such
      change was noted in the control group (32.2+/-13.4 mg/g Cr). Our study indicate
      that high levels of 5-HT in type 2 diabetics may be one of the underlying
      mechanisms of diabetic nephropathy, and that treatment with 5-HT(A2) receptor
      antagonists may reduce or inhibit the development of nephropathy.

PMID- 12213355
TI  - Prospective study of autonomic neuropathy as a predictor of mortality in patients
      with diabetes.
AB  - OBJECTIVE: The objective of this study is to evaluate whether autonomic
      neuropathy predicts short term all-cause mortality in an elderly cohort of
      veteran patients with diabetes. RESEARCH DESIGN AND METHODS: All of the diabetic
      patients receiving primary care at one VA medical center were eligible for
      participation, between 1990 and 1997. One thousand and fifteen patients were
      identified, of whom 14% declined to participate, so that a total of 843 diabetic
      patients were enrolled. Autonomic neuropathy was evaluated by heart rate response
      to timed deep breathing. One hundred and fifty one patients have died since the
      onset of the study. RESULTS: Mean follow-up was 42.4 months. Subjects who died
      had greater diabetes duration compared with survivors (13.1 vs. 11.4 years,
      P=0.04) but were comparable with regards to type of diabetes and mean
      glycosylated hemoglobin level. The Cox proportional hazards analysis, adjusting
      for age, smoking status, creatinine, pack-years of cigarettes smoked, diabetes
      duration, race, history of ischemic heart disease and hypertension showed that
      those patients with the lowest quintile of heart rate variability had a
      significantly increased risk of mortality (hazard ratio=1.49, 95% confidence
      limits 1.01-2.19). CONCLUSIONS: This study supports the hypothesis that decreased
      heart rate variability is an independent risk factor for mortality in diabetic
      patients followed in a primary care setting.

PMID- 12213356
TI  - Fasting criteria for screening: test properties and agreement with glucose
      tolerance.
AB  - The objective of this study was to characterise test properties and agreement for
      fasting glucose cut-offs used for screening diabetes in Indigenous Australian
      communities, across a range of diabetes prevalence. The oral glucose tolerance
      test (OGTT) was administered to adult volunteers (n=3249) for community-based
      diabetes screening in isolated settlements (n=25). Two-hour post-load glucose
      concentration was the 'gold standard' against which test properties were
      characterised for fasting plasma glucose cut-offs at concentrations of > or = 7.0
      mmol/l (ADA criterion) and > or = 7.8 mmol/l (WHO criterion). Test sensitivity
      (95% CI) was greater for the ADA (72.5%, 67.4-77.1%) versus the WHO criterion
      (61.5%, 56.1-66.6%). Specificity was high (>98%) using either criterion. The post
      test likelihood of diabetes, given a population prevalence of 14.8%, was 89.1%
      using the ADA criterion, and 94.9% using the WHO criterion. The ADA criterion
      gave better agreement than did the WHO criterion for diabetes prevalence > or =
      8.6%, and the probability of false results was lower using the ADA criterion,
      when diabetes prevalence was > or = 12.8%. According to the ADA criterion most
      individuals ascribed false negative results were aged > or = 35 years,
      overweight/obese, or had impaired fasting glucose. The fasting glucose criterion
      of 7.0 mmol/l was superior to 7.8 mmol/l in screening for diabetes.

PMID- 12213357
TI  - Is there a need for changes in renal biopsy criteria in proteinuria in type 2
      diabetes?
AB  - Criteria for renal biopsy in proteinuric type 2 diabetes mellitus (T2DM) patients
      have been not defined. Usually criteria for renal biopsy in type 1 diabetes
      mellitus (T1DM) are used (microhaematuria, absence of diabetic retinopathy (DR),
      uncharacteristic change in renal function or immunological abnormalities). The
      aim of this study was to reconsider the indications for renal biopsy in T2DM
      using T1DM criteria, to determine whether they are useful in identifying patients
      with potentially treatable lesions. We studied 127 proteinuric patients with
      T2DM. Renal biopsy was performed in 35 who met the criteria for biopsy. Biopsy
      revealed diabetic glomerulopathy (DG) in 29 (83%) (in three associated with
      nondiabetic renal disease), immunoglobulin A (IgA) glomerulonephritis in three,
      focal glomerulosclerosis in one and normal glomeruli in two. DG was diagnosed in
      17 (74%) of the patients without DR, in 18 (78%) of the patients with
      microhaematuria and in 10 (67%) of the patients with microhaematuria and without
      DR. All patients with DR had DG alone, except three with sudden unexpected
      changes in renal function. We conclude that DG is the most commonly found renal
      lesion in T2DM patients with proteinuria biopsied according to T1DM criteria,
      even in patients with microhaematuria or without retinopathy. Thus, these biopsy
      criteria are not useful in identifying patients with potentially treatable other
      renal diseases.

PMID- 12213358
TI  - Imaging features of esophageal leiomyomatosis: a case report.
AB  - Leiomyomas are the most common benign tumors of the esophagus. However,
      esophageal leiomyomatosis is a rare pathologic entity that has received little
      attention in the radiologic literature. We present a case of esophageal
      leiomyomatosis with imaging features on barium swallow and computed tomography
      (CT).

PMID- 12213359
TI  - Hemoptysis demonstrated on Tc99m-sulfur colloid scanning: a rare complication of
      amoebic liver abscess.
AB  - We report the finding of bleeding into right lung from a ruptured amoebic liver
      abscess. A 25-year-old male presented with pain in the right lower chest and
      cough associated with expectoration of chocolate-colored sputum. Radiographs of
      chest showed right-sided pleural effusion. Serial images of Tc99m-sulfur colloid
      study revealed progressive accumulation of radiotracer in the upper photopenic
      area extending into the right lung region suggestive of active bleeding from the
      abscess cavity.

PMID- 12213360
TI  - A case report of an unusual location of pericruciate meniscal cyst with adjacent
      bony erosion.
AB  - Meniscal cysts are uncommon cystic lesions around the knee, and pericruciate
      meniscal cysts are the most rare types. Here we present an unusual case of a
      pericruciate meniscal cyst located laterally to the anterior cruciate ligament
      (ACL), causing erosion of the adjacent tibial plateau.

PMID- 12213361
TI  - Arachnoid cyst of the frontal part of the temporal lobe producing exopthtalmos CT
      and MRI evaluation.
AB  - Twenty-three patients with an arachnoid cyst in the frontal part of the temporal
      bone, which produced exopthtalmos, were evaluated with CT and MRI. The majority
      of the patients had the peak of the bowing of the bony orbit wall in the
      posterior third (20/23) and only three in the middle. Arachnoid cyst are
      classified as small (13/23), medium (5/23) or large (5/20) size. Exopthtalmos are
      also classified as mild, moderate or large. CT and MRI clearly revealed the
      exopthtalmos, the bone remodelling process and the relationship of the orbit
      muscles, optic nerve and posterior bony wall of the orbit.

PMID- 12213362
TI  - Accidental ureteral ligation during an inguinal hernia repair of patient with
      crossed fused renal ectopia.
AB  - Because most of the presenting symptoms of ureteral herniation and crossed renal
      ectopia are nonspecific, it is important to be aware of their presence and
      association to avoid iatrogenic injuries to the kidneys and/or the ureters. We
      present the imaging findings of a patient with ureteral ligation whose ureteral
      herniation and crossed renal ectopia were identified after undergoing hernia
      repair.

PMID- 12213363
TI  - Gynecomastia in male HIV patients MRI and US findings.
AB  - PURPOSE: To evaluate the role of MRI and sonography in differential diagnosis
      between gynecomastia and lipomastia in adult male HIV patients treated with high
      activity antiretroviral therapy (HAART) for guide management. MATERIALS AND
      METHODS: Nineteen adult male HIV patients with enlargement of the breast, which
      developed during treatment with HAART, were examined with ultrasound (US) and
      magnetic resonance imaging (MRI). RESULTS: MRI was performed with SPIR T2WI,
      depicted in 95% of the patients, true gynecomastia and in the remaining 5%
      lipomastia; US demonstrated in all patients, in the subareolar region, a
      hypoechoic area, but was enable to make a differential diagnosis between
      glandular tissue and fat accumulation. CONCLUSION: US and MRI scan should be
      advised in HIV-infected patient in antiretroviral therapy with enlargement of the
      breast, in order to assess the best choice in managing this clinical condition.
      MRI with fat saturation sequences clarifies the tissue distribution in the
      mammary gland and helps to assess the amount of fat accumulated in the breast.

PMID- 12213364
TI  - Subacute osteomyelitis of long bones: diagnostic usefulness of the "penumbra
      sign" on MRI.
AB  - Although subacute osteomyelitis of long bones is not uncommon, it is usually
      confined to metaphysis. Two unusual cases of subacute osteomyelitis that
      traversed a growth plate are described. There may be some radiological
      difficulties in distinguishing it from other malignant or benign lesions. On
      magnetic resonance (MR) imaging, both of the present cases showed characteristic
      four-layered appearance and the penumbra sign. These characteristic findings on
      MR imaging are considered to facilitate establishing the radiologic diagnosis.

PMID- 12213365
TI  - Contrast-enhanced power Doppler US: is it useful in the differentiation of
      gallbladder disease?
AB  - Thirteen patients with gallbladder disease underwent power Doppler ultrasound
      (PDUS) before and after microbubble contrast agent injection. Lesion and liver
      bed vascularity was evaluated. Pathological diagnoses in nine patients were two
      acute cholecystitis, four chronic inflammation, one adenoma and two
      adenocarcinoma. Two cases of cancer were included on clinical and radiological
      findings. Two cases were excluded because no pathologic diagnosis was available.
      Liver bed hyperemia was noted only in acute cholecystitis. Contrast-enhanced PDUS
      was superior to nonenhanced PDUS in the demonstration of vascularity of
      gallbladder diseases. However, contrast-enhanced PDUS has limited value in the
      differentiation.

PMID- 12213366
TI  - The endometrium on routine contrast-enhanced CT in asymptomatic postmenopausal
      women: avoiding errors in interpretation.
AB  - We studied 54 asymptomatic postmenopausal women to characterize normal contrast
      enhanced computed tomography (CT) appearance of endometrium. Endometrium was
      visualized in 26 out of 54 (48.1%) women, and when seen its mean short-axis
      thickness was 7.5 mm. The anteroposterior thickness varied directly with uterine
      angulation (P<.05). Endometrial attenuation was significantly less than that of
      the myometrium (P<.05). Endometrial thickness (short axis) and attenuation were
      inversely correlated to patient age and to years after menopause (P<.05). We
      believe that our findings will help prevent overdiagnosis of endometrial fluid or
      thickening in asymptomatic women.

PMID- 12213367
TI  - Magnetic resonance imaging characteristics of hyperacute hemorrhage in the brain
      and spine.
AB  - Five distinct stages have been defined for the magnetic resonance (MR) appearance
      of intraparenchymal hematomas in the brain: hyperacute, acute, early subacute,
      late subacute and chronic. Despite the extensive study of the evolution of
      hematomas there has been little attention given to the MR appearance of the
      posthemorrhagic state within the initial hours after the hemorrhage occurs. We
      discuss and illustrate the MR imaging characteristics of hyperacute hemorrhage.
      Five cases of hyperacute intraparenchymal hemorrhage, one intracranial subdural
      and one intraspinal lumbar epidural hemorrhage are presented.

PMID- 12213368
TI  - Metastatic chondrosarcoma to the lung with extension into the left atrium via
      invasion of the pulmonary veins: presentation as embolic cerebral infarction.
AB  - We present a case of metastatic chondrosarcoma to the lungs that invaded the left
      inferior pulmonary vein, extended into the left atrium and presented with an
      embolic cerebral infarct. CT findings included a large mass in the left lower
      lobe associated with enlargement of the left inferior pulmonary vein and a
      lobular filling defect in the left atrium. Systemic arterial embolization and
      obstruction of the mitral valve may be prominent features of pulmonary tumors
      that have invaded the pulmonary veins.

PMID- 12213369
TI  - Bipositional MR imaging vs arthrography for the evaluation of femoral head
      sphericity and containment in Legg-Calve-Perthes disease.
AB  - Eleven hips of 10 patients with Legg-Calve-Perthes disease (LCPD) were examined
      by arthrography and magnetic resonance (MR) imaging. Arthrogram and MR images
      were obtained with the hips in neutral position and in 20 degrees flexion
      abduction and internal rotation. Modified arthrographic index (AI) was used for
      the evaluation of sphericity and acetabulum head index (AHI) was used for the
      assessment of containment. According to AI, there is no significant difference
      between the arthrograms and coronal MR imaging, but the difference between the
      coronal and sagittal MR imaging was significant. There was no statistical
      difference between the arthrograms and MR measurements in terms of AHI. Anterior
      flattening of the femoral head and the effect of hip flexion in the containment
      at the sagittal plane could be demonstrated clearly in sagittal MR imaging. Even
      if there was significant flattening in coronal plane, the sphericity of the head
      was preserved in the sagittal plane. Bipositional MR imaging is comparable to
      arthrography for the demonstration of sphericity and containment of the femoral
      head in both coronal and sagittal planes in LCPD.

PMID- 12213370
TI  - Inguinoscrotal bladder herniation: is CT a useful tool in diagnosis?
AB  - Urinary bladder herniation into the inguinal canal is a rare occurrence. The
      condition is often diagnosed during inguinal hernia surgery. We present a rare
      case of inguinoscrotal bladder herniation with its computed tomography findings.

PMID- 12213371
TI  - Lung scan in the diagnosis and management of patent foramen ovale pulmonary
      embolism, paradoxical embolism.
AB  - This case illustrates the reopening of foramen ovale in a young patient with
      chronic pulmonary hypertension caused by bronchiectasis and chronic pulmonary
      fibrosis, which resulted in a prominent right-to-left shunt and severe hypoxia.
      Her clinically unsuspected right-to-left shunt was discovered during ventilation
      perfusion scan, which was performed for the evaluation of pulmonary embolism. She
      had common variable immune deficiency, a primary immunodeficiency disease in
      which B-lymphocytes produce few or no antibodies. Most patients with this
      syndrome have an intrinsic defect in their B-lymphocytes that results in reduced
      immunoglobulin production. In these patients, recurrent respiratory tract
      infections are common and may result in chronic lung disease, fibrosis,
      particularly bronchiectasis (20-30%) and even cor pulmonale as happened in our
      patient [J. Clin. Immunol. 9 (1989) 22-33.].

PMID- 12213372
TI  - Cerebral hydatid disease CT and MR findings.
AB  - In this study, we reviewed the computed tomography (CT, n=9) and magnetic
      resonance (MR, n=5) imaging findings of 11 patients with pathologically confirmed
      cerebral hydatid disease. Among our patients, there were 10 cases of Echinococcus
      granulosus and 1 case of Echinococcus multilocularis. Common CT and MR imaging
      findings of E. granulosus lesions were well-defined, smooth thin-walled,
      spherical, homogeneous cystic lesions with no contrast enhancement, no
      calcification, and no surrounding edema. E. multilocularis lesions showed
      calcified round, solid pattern with definite margins, contrast enhancement, and
      surrounding edema.

PMID- 12213382
TI  - Ligand binding and activation of the Ah receptor.
AB  - The Ah receptor (AhR) is a ligand-dependent transcription factor that can be
      activated by structurally diverse synthetic and naturally-occurring chemicals.
      Although a significant amount of information is available with respect to the
      planar aromatic hydrocarbon AhR ligands, the actual spectrum of chemicals that
      can bind to and activate the AhR is only now being elucidated. In addition, the
      lack of information regarding the actual three-dimensional structure of the AhR
      ligand binding domain (LBD) has hindered detailed analysis of the molecular
      mechanisms by which these ligands bind to and active AhR signal transduction. In
      this review we describe the current state of knowledge with respect to naturally
      occurring AhR ligands and present and discuss the first theoretical model of the
      AhR LBD based on crystal structures of homologous PAS family members.

PMID- 12213383
TI  - The role of chaperone proteins in the aryl hydrocarbon receptor core complex.
AB  - The aryl hydrocarbon receptor (AhR) exists in the absence of a ligand as a
      tetrameric complex composed of a 95-105 kDa ligand binding subunit, a dimer of
      hsp90, and the immunophilin-like X-associated protein 2 (XAP2). XAP2 has a highly
      conserved carboxy terminal tetratricopeptide repeat domain that is required for
      both hsp90 and AhR binding. Hsp 90 appears to be involved in the initial folding
      of newly synthesized AhR, stabilization of ligand binding conformation of the
      receptor, and inhibition of constitutive dimerization with ARNT. XAP2 is capable
      of stabilizing the AhR, as well as enhancing cytoplasmic localization of the
      receptor. XAP2 binds to both the AhR and hsp90 in the receptor complex, and is
      capable of independently binding to both hsp90 and the AhR. However, the exact
      functional role for XAP2 in the AhR complex remains to be fully established.

PMID- 12213384
TI  - The mechanism of AH receptor protein down-regulation (degradation) and its impact
      on AH receptor-mediated gene regulation.
AB  - The proteolytic degradation of transcription factors is an established mechanism
      of regulating signal transduction pathways. Recent reports have suggested that
      the aryl hydrocarbon receptor (AHR) protein is rapidly downregulated (degraded)
      following ligand binding. The downregulation of AHR has been observed in nine
      distinct cells culture lines derived from human and rodent tissues and has also
      been observed in rodent models following exposure to 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD). The downregulation of AHR appears to be ubiquitin mediated and
      occurs via the 26S proteasome pathway following nuclear export of AHR. The
      consequence of blocking AHR degradation in cell culture appears to be an increase
      in both the magnitude and duration of gene regulation by the AHR.ARNT complex.
      Thus, the physiological role of AHR degradation may be to modulate AHR-mediated
      gene regulation. This review provides analysis of the studies that have focused
      on the degradation of AHR in vivo and in vitro and the hypothesis that the
      downregulation of AHR is critical in the attenuation of AHR-mediated gene
      regulation.

PMID- 12213385
TI  - DNA binding and protein interactions of the AHR/ARNT heterodimer that facilitate
      gene activation.
AB  - Gene activation by the aryl hydrocarbon receptor (AHR) and its DNA binding
      partner, the aryl hydrocarbon receptor nuclear translocator (ARNT) requires a
      number of sequential steps that occur following the binding of ligand and entry
      of the AHR into the nuclear compartment. This includes heterodimerization of the
      AHR and ARNT, formation of the appropriate amino acid/nucleotide contacts at the
      GCGTG recognition site and interactions between either the AHR or ARNT with
      proteins that facilitate changes in chromatin structure. The majority of these
      steps are likely modulated by changes in both phosphorylation and oxidation
      status of the AHR, ARNT and associated proteins. Studies of both the basic helix
      loop-helix transcription factors and the nuclear hormone receptor family can
      provide significant insights into how this unique signaling pathway activates its
      target genes.

PMID- 12213386
TI  - Induction of cellular oxidative stress by aryl hydrocarbon receptor activation.
AB  - The aryl hydrocarbon receptor (AHR) has long been associated with the induction
      of a battery of genes involved in the metabolism of foreign and endogenous
      compounds. Depending on experimental conditions, AHR can mediate either
      activation or amelioration of chemical toxicity. For the past decade, evidence
      has mounted that AHR is associated with a cellular oxidative stress response that
      must be considered when evaluating the mechanism of action of xenobiotics capable
      of activating AHR, or capable of metabolic activation by enzymes encoded by genes
      under control of AHR. In this review, we have evaluated the diverse mechanisms by
      which AHR generates an oxidative stress response, including inflammation,
      antioxidant and prooxidant enzymes and cytochrome P450. A review of the
      regulation of Ahr transcription and functional polymorphisms especially related
      to oxidative stress is also included. We have carefully avoided placing a value
      judgment on the degree of toxicity produced by such a response, in view of the
      realization that an oxidative response is involved in many normal physiological
      processes. Since the interface between physiological, adaptive and toxicological
      responses elicited by the AHR-mediated oxidative stress response is not clearly
      defined, it behooves the researcher to evaluate both toxicological and
      physiological features of the response.

PMID- 12213387
TI  - Ah receptor and NF-kappaB interactions: mechanisms and physiological
      implications.
AB  - The aryl hydrocarbon (Ah) receptor mediates most of the toxic effects induced by
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds, which are
      ubiquitous environmental contaminants causing toxic responses in human and
      wildlife. Nuclear factor kappa B (NF-kappaB) is a pleiotropic transcription
      factor that plays a pivotal role in a wide array of physiological and
      pathological responses including immune modulation, inflammatory responses and
      apoptosis. Many physiological functions adversely affected by TCDD are also known
      to be regulated by NF-kappaB, such as immune activation, maintenance of skin
      differentiation, control of cell proliferation and survival, as well as induction
      of xenobiotic metabolizing enzymes. In the past few years, evidence has emerged
      to show that the Ah receptor and NF-kappaB interact and transcriptionally
      modulate each other. This review discusses Ah receptor-NF-kappaB interactions and
      examines potential mechanistic explanations for toxic responses as a result of
      TCDD exposure and the suppression of cytochrome P450 1A1/1A2 by stress stimuli
      such as inflammation and infection.

PMID- 12213388
TI  - Role of the aryl hydrocarbon receptor in cell cycle regulation.
AB  - Traditionally, the aryl hydrocarbon receptor (AHR) is considered to be a ligand
      activated receptor and transcription factor responsible for the induction of drug
      metabolizing enzymes. Its role in the combinatorial matrix of cell functions was
      neatly established long before the first report of an AHR cDNA sequence was
      published. Only recently, other functions of this protein have begun to be
      recognized. This review addresses novel findings relating to AHR functions that
      have resulted from experimental approaches markedly outside traditional receptor
      analyses. Here we examine the aspects of AHR biology relevant to its role in cell
      cycle regulation, from the activation of mitogen-activated protein kinases to the
      cross-talk between AHR and the RAS pathway and the functional significance of the
      interaction between AHR and the retinoblastoma protein. We have attempted to
      provide the reader with a balanced interpretation of the evidence, highlighting
      areas of consensus as well as areas still being contested.

PMID- 12213389
TI  - Aryl hydrocarbon receptors: diversity and evolution.
AB  - Animals have evolved inducible enzymatic defenses to facilitate the
      biotransformation and elimination of toxic compounds encountered in the
      environment. The sensory component of this system consists of soluble receptors
      that regulate the expression of certain isoforms of cytochrome P450, other
      enzymes, and transporters in response to environmental chemicals. These receptors
      include several members of the steroid/nuclear receptor superfamily as well as
      the aryl hydrocarbon receptor (AHR), a member of the bHLH-PAS gene superfamily.
      In addition to its adaptive functions, the AHR serves poorly understood
      physiological roles; interference with those roles by dioxins and related
      chemicals causes toxicity. One approach to understanding the physiological
      significance of the AHR is to characterize its structure, function, and
      regulation in diverse species, including mammals, birds, fish, and invertebrates.
      These animal groups include model species with unique features that can be
      exploited to broaden our understanding of AHR function. Studies carried out in
      diverse species also provide phylogenetic information that allows inferences
      about the evolutionary history of the AHR. This review summarizes the current
      understanding of AHR diversity among animal species and the evolution of the AHR
      signaling pathway, as inferred from molecular studies in vertebrate and
      invertebrate animals. The AHR gene has undergone duplication and diversification
      in vertebrate animals, resulting in at least three members of an AHR gene family:
      AHR1, AHR2, and AHR repressor. The inability of invertebrate AHR homologs to bind
      dioxins and related chemicals, along with other evidence, suggests that the
      adaptive role of the AHR as a regulator of xenobiotic metabolizing enzymes may
      have been a vertebrate innovation. The physiological functions of the AHR during
      development appear to be ancestral to the adaptive functions. Sensitivity to the
      developmental toxicity of dioxins and related chemicals may have had its origin
      in the evolution of dioxin-binding capacity of the AHR in the vertebrate lineage.

PMID- 12213390
TI  - Polymorphisms in the human AH receptor.
AB  - The AH receptor (AHR) mediates toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) as well as induction of three cytochrome P450 enzymes and certain Phase II
      enzymes. In laboratory animals, genetic variations in the AHR lead to substantial
      differences in sensitivity to biochemical and toxic effects of TCDD and related
      compounds. Relatively few polymorphisms have been discovered in the human AHR
      gene; these occur predominantly in exon 10, a region that encodes a major portion
      of the transactivation domain of the receptor that is responsible for regulating
      expression of other genes. In human populations there is a wide range of
      variation in responses regulated by the AHR for example, induction of CYP1A1.
      Some variation in human responsiveness likely is due to genetically based
      variations in AHR structure. Thus far, however, only one pair of polymorphisms,
      those at codons 517 and 570, has been shown to have a clear cut and strong effect
      on the phenotype of an AHR-mediated response. The search continues for
      polymorphisms that alter AHR function because this receptor is a central factor
      in determining responses to important environmental contaminants and also plays a
      physiologic role in early development in mammals.

PMID- 12213391
TI  - Quillaja saponin adjuvants: derivatives formed under sub-optimal conditions.

PMID- 12213392
TI  - The effect of recombinant plasmids on in vivo colonisation of Salmonella enterica
      serovar Typhimurium strains is not reflected by in vitro cellular invasion
      assays.
AB  - Attenuated strains of Salmonella enterica serovar Typhimurium are used as
      carriers of heterologous antigens as candidate oral vaccines and, more recently,
      as carriers of DNA vaccines. In this study, recombinant Salmonella strains that
      were altered in their ability to colonise murine tissues in vivo when compared to
      parent strains were not, however, equally altered in their ability to invade
      murine cells in vitro. These results suggest that in vitro invasion studies may
      not be a representative model for colonisation of tissues in vivo, and that in
      vitro studies should ideally be used in conjunction with in vivo studies for the
      assessment of potential Salmonella vaccines.

PMID- 12213393
TI  - Construction and immunogenicity of a codon-optimized Entamoeba histolytica Gal
      lectin-based DNA vaccine.
AB  - Invasive amebiasis caused by Entamoeba histolytica is the third leading parasitic
      cause of mortality, and there are no vaccines available to help control the
      disease. The galactose-adherence lectin (Gal-lectin) is the parasite's major
      molecule allowing it to adhere to colonic mucin for colonization and to target
      cells for tissue destruction. It is immunodominant and is regarded as the most
      promising candidate molecule to be included in a subunit vaccine against
      amebiasis. In this study, we are reporting the construction of a codon-optimized
      DNA vaccine encoding a portion of the Gal-lectin heavy subunit that includes the
      carbohydrate recognition domain (CRD), and its in vivo testing in mice. The
      vaccine stimulated a Th1-type Gal-lectin-specific cellular immune response as
      well as the development of serum antibodies that recognized a recombinant portion
      of the heavy subunit, and that inhibited the adherence of trophozoites to target
      cells in vitro.

PMID- 12213394
TI  - Community interventions and the epidemic prevention potential.
AB  - Evaluation of community-level effects of intervention programs in infectious
      diseases is receiving increased attention. In this paper, we consider evaluation
      of the community-level effectiveness measures on the example of vaccination of
      children against influenza. We introduce the concept of the epidemic prevention
      potential (EPP) as a measure of the ability of an intervention to either prevent
      transmission or at least to keep it below a pre-defined limit. As a concept to
      describe the general ability of an intervention to limit outbreaks to a certain
      defined size, the term EPP fills a void. We constructed a stochastic simulation
      model of influenza transmission and vaccination in a structured community to
      illustrate the effectiveness measures of interest and the epidemic prevention
      potential. The concepts are general and could be applied to other interventions,
      such as antivirals and quarantine.

PMID- 12213395
TI  - DNA-based vaccination against hepatitis C virus (HCV): effect of expressing
      different forms of HCV E2 protein and use of CpG-optimized vectors in mice.
AB  - DNA-based immunization may be of prophylactic and therapeutic value for hepatitis
      C virus (HCV) infection. In efforts to improve the immunogenicity of a plasmid
      expressing the second envelope protein (E2) of HCV, we evaluated in mice the role
      of the antigen localization and demonstrated that membrane-bound and secreted
      forms induced higher titers of E2-specific antibodies, as well as earlier and
      higher seroconversion rates, than the intracellular form, but all three forms
      induced strong CTL. We also investigated whether E2-specific antibody responses
      could be enhanced by CpG optimization of the plasmid backbone and showed that
      removal of neutralizing CpG dinucleotides did not have a significant effect but
      addition of 64 immunostimulatory CpG motifs significantly enhanced anti-E2
      titers. These results may have implications for the design and development of HCV
      DNA vaccines.

PMID- 12213396
TI  - Rabies intradermal post-exposure vaccination of humans using reconstituted and
      stored vaccine.
AB  - Thailand's northern Petchabun province is endemic for canine rabies. There were
      27 reported human rabies deaths between 1989 and 1998. A rabies control plan was
      formulated in 1997 between medical and veterinary public health officials. It
      started an intense education program and an ongoing dog vaccination campaign.
      Economic constraints and the high cost of biological were the main reasons for
      inadequate human post-exposure management (PET). It was therefore decided to use
      the economical Thai Red Cross Intradermal Vaccine Regimen (TRC-ID) throughout the
      province. The original TRC-ID method is only suitable for clinics that see more
      than one PET patient daily. TRC-ID was therefore modified by storing the
      reconstituted vaccine in a refrigerator for the same patient's next two visits.
      Data on a total of 8157 PET patients were collected. An additional modification
      of TRC-ID also eliminated the 90 day booster. There were no treatment failures
      and no human rabies deaths in 1999, 2000 and 2001. The modified TRC-ID method
      induces adequate levels of neutralizing antibodies, protects humans bitten by
      rabid dogs and results in significant savings in vaccine and travel costs.

PMID- 12213397
TI  - Long lasting protection against canine kala-azar using the FML-QuilA saponin
      vaccine in an endemic area of Brazil (Sao Goncalo do Amarante, RN).
AB  - Naturally exposed dogs of an endemic area were vaccinated with the fucose mannose
      ligand (FML) antigen of Leishmania donovani in formulation with QuilA saponin.
      The 100% of vaccinees were seropositive to FML and showed intradermal reaction to
      L. donovani lysate, 2 months after vaccination. The absorbency values and size of
      intradermal reaction were both significantly higher in vaccinees than in controls
      along a 3.5 years period (ANOVA, P<0.0001). The 25% of the control animals (two
      dogs on the first year and six dogs on the fourth year, respectively) and 5% of
      the vaccinees (one dog during the fourth year) developed clinical and fatal
      disease until the end of experiment. This difference was significant
      (chi(2)=3.93, P<0.05). This means that 95% protection against kala-azar was
      achieved in vaccinees, after FML-QuilA vaccination (80% of vaccine efficacy
      (VE)). Leishmania infection was also confirmed, 3.5 years after vaccination, in
      saline controls that showed positive polymerase chain reaction (PCR) for
      Leishmania DNA and FML-serology with no intradermal reaction. Higher
      seropositivities and intradermal reactions with no Leishmanial DNA were detected
      in vaccinees. The FML-QuilA vaccine induced a significant, long lasting and
      strong protective effect against canine kala-azar in the field.

PMID- 12213398
TI  - Recombinant vaccine against hepatitis E: duration of protective immunity in
      rhesus macaques.
AB  - Hepatitis E virus (HEV) is an enterically transmitted virus that causes acute
      hepatitis. A candidate vaccine containing recombinant HEV capsid protein (56kDa)
      expressed in insect cells was shown previously to be highly immunogenic when
      administered in two doses to rhesus monkeys and to protect them from hepatitis E
      when challenged with a large intravenous dose of homologous or heterologous HEV.
      In the present study, the effect of a third dose of the same vaccine lot was
      evaluated and more importantly, the duration of protection following two doses
      was determined. Rhesus monkeys vaccinated twice with the 56kDa capsid protein
      were challenged with homologous virus 6 or 12 months after the last vaccination:
      3 of 4 monkeys challenged 6 or 12 months later, respectively were protected
      against viral hepatitis. Similarly, all four of the rhesus monkeys given a third
      dose of vaccine 1 month prior to challenge were protected against hepatitis. In
      contrast, all four monkeys given placebo developed hepatitis following challenge.
      In summary, two doses of HEV vaccine partially protected rhesus monkeys from
      hepatitis E following intravenous challenge 6 or 12 months after vaccination.

PMID- 12213399
TI  - Protective efficacy of a tandemly linked, multi-subunit recombinant leishmanial
      vaccine (Leish-111f) formulated in MPL adjuvant.
AB  - Three immunodominant leishmanial antigens (TSA, LmSTI1 and LeIF) previously
      identified in the context of host response to infection in infected donors and
      BALB/c mice, as well as their ability to elicit at least partial protection
      against Leishmania major infection in the BALB/c mouse model, were selected for
      inclusion into a subunit based vaccine. This is based on the premise that an
      effective vaccine against leishmaniasis (a complex parasitic infection) would
      require a multivalent cocktail of several antigens containing a broader range of
      protective epitopes that would cover a wide range of MHC types in a heterogeneous
      population. For practical considerations of vaccine development, we report on the
      generation of a single recombinant polyprotein comprising the sequences of all
      three open reading frames genetically linked in tandem. The resulting molecule,
      Leish-111f, comprises an open reading frame that codes for a 111kDa polypeptide.
      Evaluation of the immunogenicity and protective efficacy of Leish-111f formulated
      with IL-12 revealed that the immune responses to the individual components were
      maintained and as well, rLeish-111f protected BALB/c mice against L. major
      infection to a magnitude equal or superior to those seen with any of the
      individual components of the vaccine construct or SLA, a soluble Leishmania
      lysate. But because rIL-12 is expensive and difficult to manufacture and its
      efficacy and safety as an adjuvant for human use is questionable, we screened for
      other adjuvants that could potentially substitute for IL-12. We report that
      monophosphoryl lipid A (MPL) plus squalene (MPL-SE) formulated with rLeish-111f
      elicited protective immunity against L. major infection. The demonstrated
      feasibility to manufacture a single recombinant vaccine comprising multiple
      protective open reading frames and the potential use of MPL-SE as a substitute
      for IL-12, takes us closer to the realization of an affordable and safe
      Leishmania vaccine.

PMID- 12213400
TI  - Protection against tetanus toxin after intragastric administration of two
      recombinant lactic acid bacteria: impact of strain viability and in vivo
      persistence.
AB  - Non-pathogenic lactic acid bacteria (LAB) are attractive as live carriers to
      deliver protective antigens to the mucosal immune system. Both persisting and non
      persisting strains of lactic acid bacteria have been evaluated and seem to work
      equally well by the systemic and nasal routes of administration. However, it is
      not known if persistence and viability of the strain play a critical role when
      immunizing by the oral route. To address this question, recombinant LAB strains,
      able to persist (Lactobacillus plantarum NCIMB8826/pMEC127) or not (Lactococcus
      lactis MG1363/pMEC46) in the gastro-intestinal tract of mice and producing
      equivalent amounts of the tetanus toxin fragment C (TTFC) were compared to each
      other. A very strong ELISA TTFC-specific and protective humoral response was
      elicited by either live or UV-inactivated recombinant Lb. plantarum strains. In a
      similar protocol, recombinant Lc. lactis seemed to be somewhat less efficient
      than the former host. It is thus tempting to propose that the difference in the
      capacity of the bacterial vector to persist in the gastro-intestinal tract
      impacts on its immunogenicity and on the level of protection it may induce.
      Protection was slightly superior after administration of live strains.

PMID- 12213401
TI  - Intranasal or oral immunization of inbred and outbred mice with murine or human
      rotavirus VP6 proteins protects against viral shedding after challenge with
      murine rotaviruses.
AB  - Intranasal (i.n.) administration of an Escherichia coli-expressed chimeric VP6
      protein from the EDIM strain of murine rotavirus to adult BALB/c (H-2(d)) mice
      along with LT(R192G), an attenuated mutant of the mucosal adjuvant E. coli heat
      labile toxin, has been found to consistently stimulate ca. 99% reductions in
      rotavirus shedding after subsequent EDIM challenge. This study was designed to
      determine the robustness of this protection, i.e. can VP6 immunization
      consistently protect against shedding in this model, thus, providing an
      indication of its potential as a vaccine. Intranasal immunization with two 8.8
      microg doses of EDIM VP6 and 10 microg of LT(R192G) was found to stimulate 99%
      reductions in EDIM shedding in four additional strains of inbred mice belonging
      to three haplotypes, i.e. DBA/2 (H-2(d)), C57BL/6 (H-2(b)), 129 (H-2(b)) and C3H
      (H-2(k)). Protection stimulated against EDIM antigen shedding following i.n.
      immunization with VP6 from the human CJN strain was less (P=0.02) than induced by
      EDIM VP6 (86% versus 99%), but no further loss of protection was observed when
      the dose of CJN VP6 was reduced 100-fold. Protection against EDIM shedding was
      also maintained after i.n. immunization of three strains of outbred mice (CF-1,
      CD-1 and Swiss Webster) with either EDIM or CJN VP6, i.e. EDIM VP6 immunization
      reduced EDIM shedding by 99% while CJN VP6 immunization produced reductions of 86
      96%. Protection stimulated by oral immunization of BALB/c mice with two 8.8
      microg doses of either VP6 chimera plus LT(R192G) was not significantly different
      from that induced by i.n. immunization. Finally, protection found after either
      oral or i.n. immunization with EDIM or CJN VP6 was no different when the mice
      were challenged with McN, another strain of murine rotavirus. These results
      support further evaluation of VP6 as a vaccine.

PMID- 12213402
TI  - Comparative study of immune responses induced after immunization with plasmids
      encoding the HIV-1 Nef protein under the control of the CMV-IE or the muscle
      specific desmin promoter.
AB  - The objective of this study was to compare immune responses induced against HIV-1
      Nef after DNA immunization with Nef encoding plasmids under the control of an
      ubiquitous or a muscle-specific promoter. To this end, plasmids containing HIV-1
      nef under the control of the Cytomegalovirus or the human desmin promoters,
      specifically expressed in muscle cells, were constructed. Different groups of
      BALB/c mice were immunized with 10 or 100 microg of both constructs, controls
      were the pcDNA3 vector or the Nef protein in Freund's adjuvant (Nef-CFA). Our
      data showed that both plasmids stimulated anti-Nef humoral responses in a dose
      dependent manner. The anti-Nef antibody response, however, was earlier and higher
      with the CMV-IE promoter than with the desmin promoter. We also showed that Nef
      expressing plasmids induced high titers of anti-Nef antibodies (10(4)),
      comparable to those obtained in the Nef-CFA group (4x10(4)). Analysis of the
      specificity of anti-Nef antibodies revealed no influence of the promoter, and in
      contrast to Nef-CFA, plasmid immunization elicited anti-Nef antibodies directed
      principally against conformational-dependent epitopes. Data on the
      lymphoproliferative response showed that the specificity of expression, or the
      plasmid dose, did not affect the onset-time or the intensity of the response. The
      predominant IgG2a isotype of anti-Nef antibodies and the cytokine profile, mostly
      IL-2 and IFN-gamma, produced by Nef-stimulated spleen cells indicated a Th1
      response in plasmid-immunized mice, in contrast to mice immunized with Nef-CFA,
      where a Th2 response was induced. In conclusion, these data indicate that antigen
      expression by muscle cells is sufficient to stimulate a Th1 immune response.

PMID- 12213403
TI  - Cost-effectiveness of measles elimination in Latin America and the Caribbean: a
      prospective analysis.
AB  - BACKGROUND: In 1994, the Americas set a goal of interrupting indigenous measles
      transmission from the Western Hemisphere by 2000. To accomplish this goal, the
      Pan American Health Organization (PAHO) developed an enhanced measles vaccination
      strategy. METHODS: Cost data was collected at PAHO for Latin American and
      Caribbean (LAC) countries covering 96% of the region's population on components
      of the routine programs, and the 'follow-up' activities from member countries. In
      order to interpret our findings we have compared the present scenario regarding
      measles with one that would have ensued if past trends continued. RESULTS: For
      the entire LAC population, estimated cost of elimination program will be US$ 571
      million in present value terms. INTERPRETATION: The vaccination strategy toward
      achieving elimination of measles costs USD 244 million, incremental from the cost
      of vaccination before the elimination program. Within 2000-2020, the current
      program will have prevented the occurrence of 3.2 million cases of measles and
      16,000 deaths. Thus, vaccination strategy prevents a single case of measles at
      the cost of USD 71.75 and prevents a death due to measles at the cost of USD
      15,000. The case fatality rate depends on a well functioning treatment program
      for measles cases. The vaccination strategy saves a total of USD 208 million in
      treatments costs due to reduced incidence of measles.

PMID- 12213404
TI  - Liposomal immunostimulatory DNA sequence (ISS-ODN): an efficient parenteral and
      mucosal adjuvant for influenza and hepatitis B vaccines.
AB  - Synthetic oligodeoxynucleotides (ODNs) containing immunostimulatory sequences
      (ISS-ODN, also known as CpG-ODNs) have been shown to display in experimental
      models potent Th1-biassed immunoadjuvant activity upon parenteral or mucosal co
      administration with a variety of antigens. In an attempt to potentiate adjuvant
      activity, and to reduce dose and number of administrations, ISS-ODN was entrapped
      (up to 90% efficiency) in large (1.5 microm) multilamellar liposomes using a
      simple and fast (5 min) procedure. Mice were vaccinated once or twice
      intramuscularly (i.m.) or intranasally (i.n.) with subunit influenza vaccines
      (consisting of the viral hemagglutinin and neuraminidase, HN) or with hepatitis B
      surface antigen particles (HBsAg), either non-encapsulated or liposome
      encapsulated, together with free or liposomal ISS-ODN (5-25 microg per dose). At
      3-12 weeks post-vaccination, the humoral (systemic, mucosal) and cellular
      responses and protective immunity were assessed. Vaccine formulations containing
      liposomal ISS-ODN co-administered with either soluble antigen or liposomal
      antigen (in the same vesicles or in separate vesicles) were up to 30 times more
      effective than formulations containing un-encapsulated ISS-ODN in inducing: (a)
      antigen-specific serum and mucosal IgG2a and IgA antibodies; (b) splenocyte
      proliferative response, cytotoxic activity and IFNgamma production; (c) a DTH
      response; and (d) protection against virus challenge. The response was Th1
      dominant in the influenza model and a mixed Th1+Th2 response in the hepatitis B
      model. No adverse reactions were noted. Thus, liposomal encapsulation of ISS-ODN
      further enhances its inherent adjuvant activity.

PMID- 12213405
TI  - Polyacryl starch microparticles as adjuvant in oral immunisation, inducing
      mucosal and systemic immune responses in mice.
AB  - A new vaccine adjuvant for oral administration has been examined in mice.
      Polyacryl starch microparticles (2-3 microm in diameter) are prepared from a
      water-in oil-emulsion with stabilising hydrocarbon chains. A model antigen, human
      serum albumin (HSA), which is not binding to the gut epithelium, was covalently
      coupled to the highly porous starch particles. Upon oral administration, the HSA
      microparticles induced a good, diversified immune response without any signs of
      tolerance development. A strong cellular response can be detected as a delayed
      type hypersensitivity reaction. The Th1/Th2 ratio increased with the number of
      doses and time during the immunisation procedure as indicated by the subclass
      distribution of the systemic, humoral response. Furthermore, the mucosal response
      was very strong in the groups that received HSA-microparticles, while the groups
      receiving soluble HSA did not have any detectable s-IgA in faeces. The
      specificity was confirmed in an ELISPOT assay. These findings indicate that
      starch microparticles can be an interesting candidate as an oral vaccine
      adjuvant. The possible causes of the strong immune responses and the possible
      role of the dendritic cells in the diversified immune response are discussed.

PMID- 12213406
TI  - Sample size determination for phase II studies of new vaccines.
AB  - Prior to the evaluation of protective efficacy, experimental vaccines
      conventionally undergo phase II randomized controlled clinical trials to evaluate
      safety and immunogenicity. Typically, an experimental vaccine is compared to
      another vaccine or to a placebo with respect to adverse events or immune
      responses, or both. Various strategies and methods are available for design and
      analysis of such studies. A key aspect of design is the determination of sample
      size. Often a sample size is chosen that gives a high probability ("power") of
      finding a statistically significant difference in an outcome of interest, if a
      difference of a specified size exists. This approach is appropriate when the
      primary goal of the study is to demonstrate that a difference exists between two
      groups or treatments. It may not, however, give adequate assurance that a
      confidence interval around the observed difference will be narrow enough to
      exclude the possibility of an unacceptably low immune response or unacceptably
      high adverse event frequency in recipients of the experimental vaccine. In this
      paper, we apply the "non-inferiority" trial design to phase II vaccine studies;
      that is, we design the trial to rule out a difference between the vaccine and
      control in immunogenicity or reactogenicity that is considered unacceptable. We
      also consider a setting in which the desire is to show that the difference
      between immune response rates for vaccine and control is greater than a specified
      value.

PMID- 12213407
TI  - Improved cellular and humoral immune responses against Mycobacterium tuberculosis
      antigens after intramuscular DNA immunisation combined with muscle
      electroporation.
AB  - New delivery methods are needed to improve the efficiency of existing DNA
      vaccines. We have measured the immune response to Mycobacterium tuberculosis
      antigens following intramuscular DNA injection in combination with or without
      electroporation. Three to 6-fold increase in the number of antigen specific
      CD4(+) and CD8(+) T cells, measured by IFN-gamma-producing cells in an ELISPOT
      assay, was found in mice DNA injected and electroporated compared with non
      electroporated mice. Similarly, 5 to 10-fold increase in antigen specific IgG1,
      IgG2a and IgG2b antibodies were found in an immunoglobulin subclass specific
      ELISA. A 100-fold reduction in DNA dose could be used without loss of efficiency
      when immunisation was combined with electroporation. A single injection of 1
      microg of antigen 85b (ag85b) plasmid DNA was sufficient to elicit a higher and
      long lasting level of IgG2a antibodies against antigen 85B (Ag85B) compared to
      standard BCG vaccination. We conclude that DNA immunisation in combination with
      electroporation can significantly improve the immunogenicity of plasmid-based DNA
      vaccines.

PMID- 12213408
TI  - PCR-generated linear DNA fragments utilized as a hantavirus DNA vaccine.
AB  - The field of DNA vaccines has grown rapidly, and since most such vaccines involve
      the inoculation of large circular DNA molecules previously propagated in
      bacteria, several inconveniences (e.g. the presence of antibiotic resistance
      genes, impurities from bacterial cultures or inefficient uptake of the large and
      bulky plasmid DNA molecules to the nucleus) are debated. In this study, we have
      explored the possibility of using smaller and more flexible PCR-generated linear
      DNA fragments instead. Phosphorothioate (PTO)-modified primers were used
      successfully to protect the PCR-generated DNA fragments from exonuclease
      degradation, and by using a nuclear localization signal-peptide to target the
      linear DNA to the nucleus the immune response against the encoded antigen was
      further improved. This approach was tested in cell culture using a sensitive
      reporter system and in vivo with DNA encoding the amino-terminus of the Puumala
      hantavirus nucleocapsid protein. Our results indicate that linear DNA fragments
      have a great potential as a genetic vaccine and phosphorothioate modification in
      combination with a nuclear localization signal peptide increase the stability and
      targets the linear DNA molecules to the nucleus resulting in an improved
      biological response examined both in vitro and in vivo.

PMID- 12213409
TI  - Synergistic adjuvant activity of immunostimulatory DNA and oil/water emulsions
      for immunization with HIV p55 gag antigen.
AB  - A synthetic oligonucleotide containing a previously identified adjuvant active
      CpG DNA sequence was evaluated for its ability to augment antibody and CTL
      responses to p55 gag from HIV-1 in mice. Surprisingly, the CpG oligonucleotide,
      although, it had previously been described as the most potent adjuvant sequence
      in mice for the particulate HbsAg, was ineffective when used in a simple
      combination with urea-solubilized p55 antigen. However, a potent adjuvant effect
      was observed with the CpG sequence when it was formulated with emulsions.
      Enhancement of antibody titer by CpG emulsion formulations was observed with urea
      solubilized p55 antigen, however, significantly higher titers were obtained with
      p55 bound to polylactide-co-glycolide microparticles. In both cases IgG2a was
      enhanced in the presence of CpG. It appears likely that presentation of CpG with
      emulsions and particulate antigens enhances their delivery into antigen
      presenting cells (APC) and results in more effective presentation of antigen and
      adjuvant. To support this hypothesis, preliminary in vitro studies were
      undertaken to show upregulation of CD86 on mouse bone marrow-derived dendritic
      cells (BMDC) in vitro, following incubation with CpG formulations.

PMID- 12213410
TI  - Electroporation improves the efficacy of DNA vaccines in large animals.
AB  - It is generally recognized that DNA vaccines are often less effective in large
      animals than in mice. One possible reason for this reduced effectiveness may be
      transfection efficiency and the low level of expression elicited by plasmid
      vectors in large animals. A possible way to improve plasmid gene expression in
      vivo is electroporation. To determine whether we could enhance immune responses
      in pigs by electroporation, we used plasmids encoding two different genes (bovine
      herpesvirus glycoprotein D (gD) and hepatitis B surface antigen (HBsAg)) and two
      different electrodes, a single-needle electrode and a six-needle electrode.
      Electroporation significantly enhanced immune responses to both antigens. In
      addition, we demonstrated that co-administration of plasmids coding for two
      different antigens (pgD and pHBsAg) did not result in significant interference
      between the plasmids. We also incorporated a DNA prime/protein boost strategy to
      examine the effect of DNA priming with electroporation on the immune response
      after a protein boost.

PMID- 12213411
TI  - Anaphylactic reaction to diphtheria-tetanus vaccine in a child: specific IgE/IgG
      determinations and cross-reactivity studies.
AB  - The present study describes the occurrence of an anaphylactic reaction after the
      administration of the fifth booster dose of DT vaccine in a six-year-old child.
      Skin test, in vitro determinations of specific IgE antibodies and immunoblotting
      assays showed that the IgE response was directed against tetanus and diphtheria
      toxoids (Dtx). IgG antibodies were also detected by ELISA and immunoblotting. The
      RAST and immunoblotting inhibitions showed no cross-reactivity between the two
      toxoids, indicating the presence of co-existing but non-cross-reacting IgE and
      IgG antibodies. This was maintained in two subsequent determinations done 18 and
      30 months after the episode. To our knowledge, this is the first study of cross
      reactivity between tetanus and diphtheria antigens. We show that simultaneous IgE
      antibodies to two different toxoids may occur, indicating that after an immediate
      reaction to DT, a search for IgE antibodies to both tetanus and Dtx should be
      undertaken.

PMID- 12213412
TI  - Development of HIV-1 Nef vaccine components: immunogenicity study of Nef mutants
      lacking myristoylation and dileucine motif in mice.
AB  - In an effort to develop a safe Nef component for use in Cytotoxic T-lymphocyte
      (CTL)-based HIV-1 vaccines, several versions of Nef constructs lacking
      myristoylation and dileucine motif were engineered and their abilities to elicit
      T cell responses were evaluated in mice. Nef-specific murine T cell epitopes were
      first mapped in three strains of mice (Balb/c, C3H/HeN and C57BL/6), and a pair
      of dominant Nef-specific CD4(+) and CD8(+) T cell epitopes were identified in
      C57BL/6 mice. C57BL/6 mice were subsequently immunized with engineered Nef DNA
      constructs, and Nef-specific CD4(+) and CD8(+) T cell responses were determined.
      A Nef mutant with simple alanine substitutions at the myristoylation and
      dileucine sites was impaired in its ability to elicit Nef-specific CD4(+) and
      CD8(+) T cell responses. Addition of human tissue plasminogen activator (TPA)
      leader sequence to the N terminus of Nef, which concomitantly inactivates the
      myristoylation site, significantly enhanced the Nef-specific T cell responses.
      These findings may have practical implications for developing HIV-1 Nef vaccine
      component.

PMID- 12213413
TI  - A novel recombinant vaccine which protects mice against ricin intoxication.
AB  - Ricin toxin (RT) is a plant-derived toxin of extraordinary toxicity; a single
      molecule successfully internalized into the cytoplasm of a cell is lethal for
      that cell. An estimated dose of 1-10 microg/kg is lethal to humans, making
      aerosolized ricin a potential agent for bioterrorism. Vaccination against ricin
      using either denatured toxin or its modified A chain subunit (RTA) has been
      successful in experimental animals but both vaccines have potential toxicities.
      Recombinant (r) RTA has not been evaluated as a vaccine. However, the advantage
      of such a vaccine is that these potential toxicities can be deleted by
      appropriate mutations. In this study we have generated three mutants and shown
      that two lack toxicity as compared to the wild type rRTA. These mutants induce
      protective humoral immune responses in mice. One or both should be considered for
      use in humans.

PMID- 12213415
TI  - A comprehensive classification of craniofacial fractures: postmortem and clinical
      studies with two- and three-dimensional computed tomography.
AB  - A comprehensive classification of midfacial/craniofacial fractures, based on two-
      and three-dimensional computed tomography (2D and 3D-CT) is presented. We
      performed a postmortem analysis of 24 patients who had died from trauma with
      signs of craniofacial fractures, based on 2D and 3D-CT studies with
      pathoanatomical findings. In addition, CT findings for 100 patients with
      craniofacial injuries requiring an emergency CT were correlated with surgical
      findings and follow-up results. On the basis of the analysis of a total of 377
      fractures a classification system is proposed. The system is based on the use of
      the AO/ASIF (Arbeitsgemeinschaft fur Osteosynthesefragen/Association for the
      Study of Internal Fixation) scheme, defining three types (A, B, C), three groups
      within each type (e.g. A1, A2, A3) and three subgroups within each group (e.g.
      A1.1, A1.2, A1.3) with increasing severity from A1.1 (lowest) to C3.3 (highest).
      The craniofacial region is divided into three units: the lower midface (I), the
      upper midface (II) and the craniobasal-facial unit (III). Lateral and central
      fractures are also distinguished. Type A fractures are non-displaced fractures,
      type B are displaced fractures and type C are complex/defect fractures. Groups
      A1, B1 and C1 comprise fractures of an isolated unit; groups A2, B2 and C2,
      combined fractures without involvement of the skull base; and groups A3, B3 and
      C3 are those combined fractures with involvement of the skull base. A correlation
      between the severity of the fracture and (i). the number of posttraumatic
      functional limitations (Spearman rank test, correlation coefficient r=0.42),
      (ii). the need for bone grafting or dural plastic (r=0.39) and (iii). facial
      asymmetry (r=0.37), was observed. The proposed classification system allows
      standardised documentation of midfacial and craniofacial fractures, including
      those not precisely defined by the Le Fort classification scheme.

PMID- 12213416
TI  - Epidemiology of facial trauma in a sample of patients aged 1-18 years.
AB  - This study reviews the epidemiology of patients aged 1-18 years treated for
      maxillofacial injuries during a 3 year period at a tertiary care centre. Of the
      276 patients, 65.5% were aged 1-10 years. Seventy-three per cent of injuries were
      to the soft tissues and 15% of injuries were fractures. The mandible and zygoma
      were the most commonly fractured facial bones. In the adolescent group, facial
      fractures accounted for over half of all injuries. Injuries of 96.8% were classed
      as minor to moderate. Falls were by far, the commonest cause of injury, but with
      increasing age, assaults became more common. A surprisingly high incidence of dog
      bite injuries was noted, particularly in children under 7 years of age.

PMID- 12213417
TI  - Cimetidine prevents suppression of delayed hypersensitivity in an animal model of
      haemorrhagic shock.
AB  - BACKGROUND: Cimetidine reverses immunosuppression following trauma, however, its
      effect on pure haemorrhagic shock is unknown. METHODS: Mice sensitized by
      injection of sheep red blood cells (SRBCs), were subjected to cardiac puncture
      and randomized to a control group-A (n=11) and three shock groups (35% of blood
      volume extracted): group-S had no treatment (n=16), group-CP received cimetidine
      50mg/kg intraperitoneally (n=16), group-CW received oral cimetidine (200mg/kg per
      day, n=16). After 5 days, animals were challenged by injection of SRBCs into the
      foot-pad of the right hind paw (same volume of saline was injected into left
      paw). Foot-pad thickness ratios (FPTRs) were determined at 16 and 40 h, and
      inflammatory response was assessed histologically. RESULTS: At 16 h, FPTRs were
      greater in group-CW than group-S (P=0.01). There were no differences at 40 h.
      More animals in groups-CP and -CW had grade 3/4 inflammation, whilst group-S had
      the least inflammatory response (NS). CONCLUSIONS: Cimetidine prevents
      suppression of delayed hypersensitivity in this model.

PMID- 12213418
TI  - Experimental repair of segmental bone defects in rabbits by demineralized
      allograft covered by free autogenous periosteum.
AB  - Using an experimental model of segmental bone defect in the ulna of rabbits we
      investigated the effect on bone healing of fresh cancellous autograft (FCA),
      demineralized deep-frozen allograft (DDA), and demineralized deep-frozen
      allograft covered with free autogenous periosteum (DDAwP). Radiologically, it was
      found that the results of the FCA and DDAwP groups were superior to those of the
      DDA group. This superiority was statistically significant after the 3rd to the
      9th week for the FCA group, and the 6th to the 9th week for the DDAwP group.
      However, bone formation and union in the DDA group reached the same level of
      those in the other groups after 12 weeks. When the all histological findings were
      compared at the 12th week, the FCA and DDAwP groups were statistically superior
      to the DDA group in terms of proximal union. On distal union, the FCA group was
      statistically superior to the DDA group. Biomechanically, the FCA and DDAwP
      groups were statistically superior to the DDA group in terms of maximum torque
      and energy absorption. The DDAwP group was superior to the DDA group in term of
      stiffness. We conclude that ossification could be more easily achieved if
      demineralized deep-frozen allograft is covered with periosteum when faced with
      the need for quicker and better quality bone integration.

PMID- 12213419
TI  - A new method of fixation in osteoporotic bone. A preliminary report.
AB  - Over-tightening of cortical bone screws in osteoporotic bone results in weak
      fixation. Once a screw is over-tightened and the bone thread form is stripped,
      there are limited means at the surgeon's disposal to rescue the situation, none
      of them entirely satisfactory. We describe a simple device that is specifically
      designed to resolve this problem. It consists of a nylon cavity plug and
      applicator. The plug is inserted into the stripped hole and the screw re-applied
      and tightened in the normal manner. The plug expands and forms a load-bearing
      region on the inner face of the bone. Tests on osteoporotic cadavaric bone have
      shown that the plug effectively re-establishes screw fixation. When compared to
      an over-tightened screw, the plug is at least twice as resistant to loads acting
      to pull the screw out of the surrounding bone.

PMID- 12213420
TI  - Treatment of multifragmentary fractures of the femur by indirect reduction
      (biological) and plate fixation.
AB  - We present a retrospective review of the results of 43 multifragmentary femur
      fractures treated under the principle of indirect reduction (biological) and
      plate fixation. Fractures were caused by high-energy trauma in all patients.
      Sixteen were subtrochanteric, 14 diaphyseal and 13 supracondylar. There were 13
      open fractures. In six of the patients with diaphyseal fractures, a plate was
      inserted through isolated proximal and distal incisions only, deep to the vastus
      lateralis. None of the fractures was treated with bone graft. The mean follow-up
      time was 28.3 months. Union was achieved in 41 patients within a mean period of
      4.25 months. There was delayed union in one patient (subtrochanteric), non-union
      in two, infection in three, malunion in three, leg shortening in six and mild
      knee stiffness in seven. In eight patients with diaphyseal fractures in whom a
      single incision was performed, the average time for fracture healing was 4.14
      months in seven and non-union developed in one. In six patients with diaphyseal
      fractures, in whom proximal and distal incisions were performed, the average time
      for fracture healing was 4 months. There was no difference (P>0.05) between
      single and double incision with reference to infection and time to union, but the
      indirect reduction methods must be meticulously implemented. The implants we used
      are cheaper and more easily supplied than many others. The success rate is high
      when the technique is correctly implemented. We believe that this is a treatment
      of choice in countries with low socioeconomic status, no efficient health
      insurance system and no intraoperative image intensification.

PMID- 12213421
TI  - Antegrade femoral nailing: an anatomical determination of the correct entry
      point.
AB  - Operative problems in the application of femoral locking nails are frequently
      related to an unfavourable entry point at the greater trochanter. Especially in
      more distally located fractures the nail is forced to follow the cortex abutted
      medullary canal. A wrong defined entry point either in the medio-lateral or dorso
      ventral direction inevitably leads to tension between nail and femur. Forceful
      insertion in this situation may cause disastrous iatrogenic comminution at the
      fracture side or additional fractures at the proximal femur. To avoid tension
      between nail and femur the best suited entry point must be defined according to
      the natural medullary cavity. In 16 human cadaver femora, the natural medullary
      cavity was opened and after cleaning filled with a radio-opaque substance (barium
      sulphate). Twelve radiographs where taken from each bone starting with the
      anterior-posterior view and then turning the bone axially in steps of 15 degrees.
      From these radiographs, the ideal entry point at the greater trochanter was
      calculated. In 88% of the specimen the ideal entry point for a straight nail was
      found constantly at the medial border of the greater trochanter overlaying the
      tendinous insertion of the piriformis muscle. The axis of the medullary cavity
      was in average 2.1cm anterior to the dorsal border of the greater trochanter. In
      a second step the ideal entry point for bend nails was calculated. According to
      this calculation a bend nail with a radius of 100 cm needs an entry point 0.7 mm
      anterior to the dorsal edge of the greater trochanter. Overlaying the hook like
      shape of the posterior part of the trochanter.

PMID- 12213422
TI  - Retrograde intramedullary nailing of supracondylar femoral fractures: design and
      development of a new implant.
AB  - Since 1992 we have developed an implant in which the distal (condylar) screws
      have a diagonal configuration so that the screws can be closer to the distal end
      of the nail, allowing more distal fractures to be fixed. It also utilises the
      denser bone of the posterior condyles for more secure fixation in osteoporotic
      patients. The new implant was used for 24 extra-articular fractures from
      September 1994 to September 1997, and for 14 articular fractures from February
      1995 to December 2000. There was no significant difficulty with obtaining
      fixation in very distal fractures and in osteoporotic bone. Early weightbearing
      was encouraged in those with extra-articular fractures. All fractures united
      within 3 months except one which required a bone graft (but no revision of
      implant) at 6 months. Average knee flexion at final followup was 101 degrees for
      extra-articular fractures and 106 degrees for articular fractures. Complications
      included quadriceps adhesions requiring further surgery in two patients who had
      open fractures, and malunion in one patient who had an early design of the
      implant and a 4.5mm condylar screw broke. Nine patients required late removal of
      condylar screws due to local soft tissue irritation.

PMID- 12213423
TI  - Classification of trochanteric fracture of the proximal femur: a study of the
      reliability of current systems.
AB  - Five observers using the Jensen modification of the Evans classification and the
      AO classification (with and without subgroups) classified the radiographs of 88
      trochanteric hip fractures. Each observer classified the radiographs
      independently on two occasions 3 months apart. Kappa statistical analysis was
      used for determination of intra- and inter-observer variation. For the Jensen
      classification, the mean kappa value was 0.52 (range: 0.44-0.60) for intra
      observer variation and 0.34 (range: 0.17-0.38) for inter-observer variation. For
      the AO system with subgroups, the mean kappa value was 0.42 (range: 0.20-0.65)
      for intra-observer variation and 0.33 (range: 0.14-0.48) for inter-observer
      variation. For the AO classification system without subgroups, the mean kappa
      value was 0.71 (range: 0.60-0.81) for intra-observer variation and 0.62 (range:
      0.50-0.71) for inter-observer variation. We recommend classifying trochanteric
      fractures into three groups as that of the AO system without the subgroups. For
      ease of use, these three groups may be termed stable trochanteric, unstable
      trochanteric and trans-trochanteric. Neither the Jensen classification nor the AO
      classification with subgroups is an acceptable classification system for
      trochanteric hip fractures.

PMID- 12213424
TI  - The floating hip injury: patterns of injury.
AB  - OBJECTIVE: To evaluate the relationship between mechanism of injury, type of
      femoral fracture and type of acetabular fracture in floating hip injury. DESIGN:
      Historical retrospective. PATIENTS: Twenty consecutive patients who sustained a
      floating hip injury, i.e. simultaneous ipsilateral fracture of the acetabulum and
      the femur. INTERVENTION: Statistical analysis of the correlation between the
      mechanism of injury and fracture type. RESULTS: Two main patterns of floating hip
      injury were observed. The first is the posterior type, which occurs due to a
      longitudinal force along the femur that causes first, a posterior type fracture
      of the acetabulum and thereafter, a midshaft femoral fracture. The second pattern
      is the central type, caused by a lateral blow to the greater trochanter, which
      then causes a central fracture-dislocation of the acetabulum and a proximal
      fracture of the femur. CONCLUSIONS: This observation explains the biomechanical
      nature of this injury and has treatment related implications.

PMID- 12213425
TI  - Radiation exposure to surgeon and patient in intramedullary nailing of the lower
      limb.
AB  - Intramedullary nailing is probably the best method of treating long bone
      fractures in the lower limb. The operation is guided by fluoroscopy, for guide
      wire insertion, fracture reduction and distal locking. No study so far has
      measured the scatter radiation to the patient's gonads during intramedullary,
      particularly femoral, nailing. The purpose here was to estimate the radiation
      hazard to the patients' gonads and surgeons' hands during intramedullary nailing
      for lower limb fractures. From April 1994 to June 1998, 184 consecutive patients
      had 224 nailings for lower limb fractures. Twenty-eight patients had Marchetti
      Vincenzi nails and the rest had Russell-Taylor nails. There were 45 males and 40
      females who had femoral nailing and 71 males and 28 females who had tibial
      nailing. The mean (range) age for femoral nailing was 56 (17-95.5) years and the
      mean age for tibia nailing was 44 (16.5-87.5) years. The average time of
      radiation when done by consultants was half that of middle-grade surgeons. The
      mean tibial nailing radiation time for the consultant was 0.56 min and for the
      middle-grade 1.28 min. The mean femoral nailing radiation time for the consultant
      was 0.52 min and for the middle-grade 1.61 min (P<0.05). The mean tibial and
      femoral nailing time were less for Marchetti nailing (P<0.05). Regular protection
      of the gonads of these patients is mandatory. This study shows that the radiation
      exposure for Marchetti-Vincenzi nailing is significantly less than for Russell
      Taylor nailing. The overall radiation to patient gonads and surgeon hands was
      within acceptable limits.

PMID- 12213426
TI  - Do type B malleolar fractures need a positioning screw?
AB  - Type B malleolar fractures (AO/ASIF classification) are usually stable ankle
      joint fractures. Nonetheless, some show a residual instability after internal
      fixation requiring further stabilization. How often does such a situation occur
      and can these unstable fractures be recognized beforehand?From 1995 to 1997, 111
      malleolar fractures (three type A, 90 type B, 18 type C) were operated on.
      Seventeen out of 90 patients (19%) with a type B fracture showed residual
      instability after internal fixation (one unilateral, four bimalleolar and 12
      trimalleolar fractures). Five of these patients showed a dislocation in the
      sagittal plane (anteroposterior) clinically or on the radiographs, five a
      dislocation in the coronal plane with dislocation of the tibia on the medial
      aspect of the ankle joint, and four an incongruency on the medial aspect of the
      joint. In three cases, no preoperative abnormality indicating instability was
      found. The fractures were all fixed using an additional positioning screw. In 11
      patients, the positioning screw was removed after 8-12 weeks, in six patients
      removal was performed after 1 year along with removal of the plate. All 17
      patients were reviewed 1 year after internal fixation, 16/17 showed a good or
      excellent result with identical or only minor impairment of range of motion of
      the ankle joint. CONCLUSION: Unstable ankle joints after internal fixation of
      type B malleolar fractures exist. Residual instability most often occurs after
      trimalleolar fractures with initial joint dislocation. Treatment with an
      additional positioning screw generally produced a satisfactory result.

PMID- 12213427
TI  - Intercondylar fractures of the femur in the elderly: a treatment option.

PMID- 12213428
TI  - Cement restriction technique in dynamic hip screw revisions.
AB  - When revising dynamic hip screw fixation to arthroplasty, the defect left by the
      lag screw in the proximal femur poses a problem for cement containment, with the
      potential for sub-optimal cementation. We recommend the use of a bioresorbable
      cement restrictor as a simple and effective means to overcome this problem.

PMID- 12213429
TI  - The lipids that matter from infant nutrition to insulin resistance.
AB  - Breast-fed infants showed decreased incidence of obesity, hypertension, diabetes
      mellitus, and coronary heart disease in later life and higher cognitive function.
      Breast milk is rich in long-chain polyunsaturated fatty acids (LCPUFAs) and brain
      preferentially accumulates LCPUFAs during the last trimester of pregnancy and the
      first few months of life. Breast-fed infants showed significantly lower plasma
      glucose levels and higher percentage of docosahexaenoic acid and total
      percentages of LCPUFAs in their skeletal muscle biopsies compared with formula
      fed. LCPUFAs suppress the production of pro-inflammatory cytokines, regulate the
      function of several neurotransmitters, enhance the number of insulin receptors in
      the brain and other tissues, and decrease insulin resistance. LCPUFAs may enhance
      the production of bone morphogenetic proteins (BMPs), which participate in
      neurogenesis. It is proposed that the beneficial effects of breast feeding in
      later life can be attributed to its rich LCPUFA content. It is likely that
      inadequate breast feeding results in marginal deficiency of LCPUFAs during the
      critical stages of development, which can lead to insulin resistance. Hence,
      promoting prolonged breast feeding and/or supplementing LCPUFAs during the
      critical stages of development may be beneficial in preventing insulin
      resistance.

PMID- 12213430
TI  - Red blood cell fatty acid profile of chronic renal failure patients receiving
      maintenance haemodialysis treatment.
AB  - The fatty acid profile of chronic renal failure (CRF) patients on maintenance
      haemodialysis treatment (MHT) is abnormal and results point towards an essential
      fatty acid (EFA) deficiency. However, controversies still exist as to which of
      the essential fatty acids (EFAs) or EFA-products are decreased. In this study,
      the results of a comprehensive analysis of the fatty acids, performed on the red
      blood cells of 14 CRF patients on MHT, are presented. The red blood cell membrane
      fatty acids determined in this study include a range of saturated fatty acids
      (SFAs), mono-unsaturated fatty acids (MUFAs) and poly-unsaturated fatty acids
      (PUFAs). Results confirmed the suggested presence of an essential fatty acid
      deficiency in CRF patients on MHT. It showed the total content of the n-6 fatty
      acids (31.66 +/- 3.21 vs 34.67 +/- 2.05), as well as the total content of the
      PUFAs (37.22 +/- 4.08 vs 40.93 +/- 2.35), to be significantly decreased. The
      total MUFA content was, in contrast, significantly increased (16.87 +/- 0.91 vs
      15.49 +/- 1.18). The EFA deficiency profile seen in this study points towards
      that of a chronic inflammatory condition. This is borne out by the fact that all
      three precursors of the eicosanoids--the mediators of various inflammatory and
      immune responses--were reduced in the presence of an increase in MUFAs as well as
      SFAs. The possibility of the fatty acid profile of CRF patients on MHT being that
      of a chronic inflammatory condition is supported by the fact that continuous
      complement-dependent and complement-independent immune activation, due to bio
      incompatibility between blood cells and the dialysis membranes, is known to occur
      during the dialysis process.

PMID- 12213432
TI  - The 5' region of the human thromboxane A(2) receptor gene.
AB  - Thromboxane is an important modulator of hemostasis and smooth muscle tonus and
      signals via G-protein-coupled thromboxane receptor. Previously, we characterized
      the TP receptor gene and suggested the presence of three promoter regions within
      the gene. The aim of the present study was to examine the regulation of
      transcriptional gene expression. By primer extension experiments the major
      transcription initiation site was shown to be a doublet at -160/165 bp upstream
      of the ATG codon in human megakaryoblastic MEG-01 cells, endothelial ECV 304
      cells and in human myometrium smooth muscle cells. In the erythroleukemic HEL 1
      cells transcription initiation site was identified at -10 bp. Transcriptional
      activity of the three 5'flanking regions of TP receptor gene representing the
      putative promoter regions was evaluated by transfection of MEG-01 cells with
      chimeric constructs containing luciferase gene-encoding sequence. Promoter region
      I displayed highest transcriptional activity and RT-PCR analysis confirmed the
      transcription of TP receptor mRNA driven by promoter I. Although, weak
      transcriptional activity was also observed regarding promoter region II, we were
      unable to amplify cDNA fragments representing promoter II-driven mRNA synthesis.
      Considering promoter region III, transcriptional activity was barely detectable.
      Various deletions of the 3.9 kb promoter I region revealed a size-dependent
      transcriptional activity. Further, for full activity a 'core' promoter
      corresponding to the region from -160/165 to -588 bp appeared to be necessary for
      full transcriptional activity of promoter 1.

PMID- 12213431
TI  - D-003, a potential antithrombotic compound isolated from sugar cane wax with
      effects on arachidonic acid metabolites.
AB  - D-003 is a natural mixture of higher primary saturated aliphatic acids purified
      from sugar cane wax, whose main component is octacosanoic acid followed by
      triacontanoic, dotriacontanoic, and tetratriacontanoic acids. D-003 inhibits
      platelet aggregation and arterial thrombosis experimentally induced in a dose
      dependent fashion. This study was undertaken to investigate the effects of D-003
      (25 and 200 mg/kg) in experimental models of venous thrombosis and on plasma
      levels of two metabolites from arachidonic acid (AA) : thromboxane A(2) (TxA(2))
      and prostacyclin (PgI(2)). D-003 orally administered as single doses of 200
      mg/kg, but not at 25 mg/kg, significantly increased plasma levels of 6 keto
      PgF1alpha levels, a stable metabolite of PgI(2) in PPP obtained from collagen
      stimulated blood (4 microg/ml) compared with control group. Nevertheless, levels
      of 6 keto PgF1alpha levels determined after 10 days of oral treatment with both
      doses of D-003 were significantly larger than those of the controls. Likewise,
      single and repeated oral doses of D-003 (25 and 200 g/kg) significantly reduced
      the TxB(2) and MDA plasma levels obtained from whole blood stimulated by
      collagen. Hence, TxB(2)/6 keto PgF1alpha ratio significantly decreased in animals
      treated with D-003. Single and repeated oral doses of D-003 (25 and 200 mg/kg)
      significantly reduced the weight of venous thrombus experimentally induced in
      rats. D-003 at single doses (400 mg/kg but not 200 mg/kg) significantly protected
      from death induced by endovenous infusion of collagen plus epinephrine in mice.
      The present results support that these effects of D-003 on AA metabolites could
      explain, at least partially, its antiplatelet and antithrombotic effects.

PMID- 12213433
TI  - Efficacy of carnitine in the treatment of children with attention-deficit
      hyperactivity disorder.
AB  - To determine safety and the efficacy of carnitine treatment in children with
      attention-deficit hyperactivity disorder (ADHD). The ADHD behavior was observed
      by parents completing the Child Behavior Checklist (CBCL) and by teachers
      completing the Conners teacher-rating score, in a randomized, double-blind,
      placebo-controlled double-crossover trial. In 13/24 boys receiving carnitine,
      home behavior improved as assessed with the CBCL total score (P < 0.02). In 13/24
      boys, school behavior improved as assessed with the Conners teacher-rating score
      (P < 0.05). Before treatment, the CBCL total and sub-scores were significantly
      different from those of normal Dutch boys (P < 0.0001). Responders showed a
      significant improvement of the CBCL total scores compared to baseline (P <
      0.0001). In the majority of boys no side effects were seen. At baseline and after
      carnitine treatment, responders showed higher levels of plasma-free carnitine (P
      < 0.03) and acetylcarnitine (P < 0.05). Compared to baseline, the carnitine
      treatment caused in the responsive patients a decrease of 20-65% (8-48 points) as
      assessed by the CBCL total problem rating scale. Treatment with carnitine
      significantly decreased the attention problems and aggressive behavior in boys
      with ADHD.

PMID- 12213434
TI  - Nitric oxide synthase/PGE(2) cross-talk in rat submandibular gland.
AB  - It is known that nitric oxide modulates the prostaglandin generation. However,
      little is known about the regulatory action of prostaglandin on nitric oxide
      production. There is a molecular cross-talk between nitric oxide and
      prostaglandin. Here, we examined biochemical signalling pathways coupled to the
      prostaglandin E(2) (PGE(2)) receptor related to nitric oxide synthase stimulation
      in rat submandibular gland. PGE(2) through the stimulation of its own receptor,
      triggered activation of phosphoinositide turnover (IPs), translocation of protein
      kinase C (PKC), stimulation of nitric oxide synthase activity (NOS) and increased
      production of cyclic GMP (cGMP). PGE(2) stimulation of NOS and cGMP production
      was blunted by agents interfering with calcium influx, calcium/calmodulin and
      phospholipase C (PLC) activities; while PKC inhibitor was able to stimulate
      PGE(2) effects. PGE(2) did not evoke amylase release, indicating that NOS/ cGMP
      pathway were not associated with this enzyme secretion. Our results suggest that
      this prostanoid could act as vasoactive chemical mediator through its ability to
      activate NOS-cGMP pathway via own gland membrane receptor.

PMID- 12213435
TI  - Long-term administration of beraprost, an oral prostacyclin analogue, improves
      pulmonary diffusion capacity in patients with systemic sclerosis.
AB  - The objective of this study was to assess the effect of beraprost sodium, an oral
      prostacyclin analogue, on pulmonary function in patients with systemic sclerosis.
      Seventeen patients, with systemic sclerosis and predicted percent values of
      carbon monoxide diffusion capacity (%DLCO) of less than 95, received beraprost
      sodium for at least 12 months. Conventional testing for pulmonary function was
      performed at 12-month intervals and changes were evaluated with special reference
      to DLCO. Twelve patients completed the treatment. Nine patients showed
      improvement in DLCO (12.1 +/- 2.3 to 15.5 +/- 4.4 ml/min/mmHg, P < 0.006) and 10
      patients showed an increase in %DLCO (66.6 +/- 11.9 to 87.7 +/- 23.2%, P <
      0.004). Total lung capacity, vital capacity and forced expiratory volume remained
      unchanged. This study showed that DLCO levels in patients with systemic sclerosis
      improved after the administration of beraprost sodium, probably due to the
      decrease in pulmonary vascular resistance accompanied by increased cardiac
      output.

PMID- 12213436
TI  - Simultaneous quantification of prostaglandins in human synovial cell-cultured
      medium using liquid chromatography/tandem mass spectrometry.
AB  - A liquid chromatographic-tandem mass spectrometric (LC/MS-MS) method was
      developed for the simultaneous quantification of prostaglandin (PG) E(2),
      PGF(2alpha), 6-keto-PGF(lalpha) and thromboxane (TX) B(2). These eicosanoids and
      their deuterium derivatives, using as internal standards, were extracted by solid
      phase extraction and analyzed using LC/MS-MS in the selected reaction-monitoring
      (SRM) mode. A good linear response over the range of 10 pg to 10 ng for each
      eicosanoid was demonstrated. The accuracy of added eicosanoids ranged from 94.1
      to 106.6% and coefficients of variation ranged from 0.62 to 7.8%. Furthermore, we
      applied this method for the determination of eicosanoids in the human synovial
      cell-cultured medium, stimulated by lipopolysaccharide (LPS). LPS produced each
      eicosanoid and they increased in a time-dependent manner. The production levels
      after 24 h stimulation were 6-keto-PGF(1alpha) > PGE(2) > TXB(2) >> PGF(2alpha).
      This simultaneous quantification method is so useful to clarify the function of
      synovial cells in rheumatoid arthritis (RA).

PMID- 12213437
TI  - Rapid alterations of serum oxidant and antioxidant status with the intravenous
      administration of n-6 polyunsaturated fatty acids.
AB  - In an attempt to achieve the safe intravenous administration of two n-6
      polyunsaturated fatty acids (PUFAs), gamma-linolenic acid (GLA) and arachidonic
      acid (AA), and to study the subsequent changes on the total oxidant and
      antioxidant status, various steadily increasing doses of each acid were injected
      intravenously at different infusion times in 28 male rabbits. Blood samples were
      collected at 15-min time intervals by the hepatic veins and from the carotid
      artery; oxidant status was determined by the thiobarbiturate assay and total
      antioxidant status (TAS) was assessed by a colorimetric assay. Both n-6 PUFAs
      were administered with safety at a dose of 25 mg/kg within 10 min accompanied by
      an increase of malonodialdehyde concentrations in the hepatic veins and in the
      carotid artery 30-45 min, respectively, after the end of the infusion of GLA
      and/or AA. Similar changes did not occur in red cell membranes after the infusion
      of AA. TAS presented reciprocal changes to malonodialdehyde production; the main
      consumption of TAS was observed in all samples 30-60 min after the end of the
      infusion of n-6 PUFAs. The above-mentioned rapid alterations occurring in both
      serum oxidant and antioxidant status after GLA might have a future clinical
      therapeutic significance in conditions like cancer and disseminated infectious
      diseases.

PMID- 12213438
TI  - Nogo receptor mRNA expression in intact and regenerating CNS neurons.
AB  - The expression of mRNA for Nogo-66 receptor (NgR) in unoperated adult rats and
      mice, and rats with nerve grafts placed in the thalamus and cerebellum to
      stimulate axonal regeneration, was investigated by in situ hybridization. NgR was
      strongly expressed in neurons of the neocortex, hippocampal formation, and
      amygdaloid nuclei and dorsal thalamus and moderately expressed in the red nucleus
      and vestibular nuclei. NgR mRNA was expressed in cerebellar deep nuclei and more
      strongly by granule cells than by Purkinje cells. Large regions of the forebrain,
      including the striatum, thalamic reticular nucleus, hypothalamus, and basal
      forebrain showed little or no NgR expression. NgR was weakly expressed in spinal
      neurons and some primary sensory neurons. Nerve implantation into the brain did
      not affect NgR expression. Some regeneration-competent neurons expressed NgR but
      others did not. Thus NgR expression was not correlated with the ability of
      neurons to regenerate axons into nerve grafts although Nogo-66 was strongly
      upregulated by some cells in the distal stumps of injured sciatic nerves. Nogo-66
      transcripts were strongly expressed by many classes of CNS neurons and less
      strongly in white matter.

PMID- 12213439
TI  - Instrumental activation of bid by caspase-1 in a transgenic mouse model of ALS.
AB  - Transgenic expression of mutant superoxide dismutase-1 (SOD1) produces an animal
      model of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder.
      We have previously shown that the mitochondrial-dependent programmed cell death
      (PCD) pathway, including the redistribution of Bax, the cytosolic release of
      cytochrome c, and the activation of caspase-9, is recruited during
      neurodegeneration in spinal cords of transgenic mutant SOD1 mice. Herein, we show
      that the pro-PCD protein Bid is highly expressed in spinal cords of both wild
      type and transgenic mutant SOD1 mice. While full-length Bid is found in the
      spinal cord of the two groups of mice, its cleaved form is only seen in
      transgenic mutant SOD1 mice, as early as the beginning of symptoms. In contrast,
      activated caspase-8, which is known to cleave Bid, is detected only at the end
      stage of the disease. We also found that the expression of a dominant negative
      mutant of caspase-1 attenuates Bid cleavage as well as the mitochondrial release
      of cytochrome c, and the ensuing activation of caspase-9 and -3 in spinal cords
      of transgenic mutant SOD1 mice. These findings suggest that Bid cleavage may
      occur in this model by a pathway other than caspase-8 and shed light onto the
      molecular correlates of the previously reported beneficial effect of caspase-1
      inhibition in transgenic mutant SOD1 mice.

PMID- 12213440
TI  - MEGF1/fat2 proteins containing extraordinarily large extracellular domains are
      localized to thin parallel fibers of cerebellar granule cells.
AB  - The MEGF1 (protein 1 with multiple EGF-like domains) gene, which was identified
      using motif-trap screening, encodes an extraordinarily large protein containing
      two EGF-like and 34 cadherin motifs. In situ hybridization analysis revealed that
      the MEGF1 gene was specifically expressed in granule cells of the cerebellum.
      Interestingly, in the developing cerebellum, granule cells in the inner external
      germinal layer and migrating granule cells expressed MEGF1 mRNA, whereas
      proliferating cells in the outer external germinal layer did not express MEGF1
      mRNA. Expression levels in the internal granule cell layer peaked during the
      third postnatal week and remained considerably high in the adult cerebellum.
      MEGF1 protein was detected in only the cerebellum as a single 480-kDa band by
      immunoblot analyses using polyclonal antibodies against either the N-terminal or
      the C-terminal region of MEGF1 protein. Using light and electron microscopic
      immunocytochemistry, specific immunostaining of the MEGF1 protein was observed in
      the molecular layer of the cerebellum, suggesting that MEGF1 protein was
      localized in the parallel fibers of cerebellar granule cells. This was
      corroborated by results from experiments using primary dispersed cultures of
      cerebellar granule cells and cerebellar microexplant cultures. The homophilic
      interaction of MEGF1 proteins was confirmed with both a cell aggregation assay
      and an in vitro copurification assay. Based on these results, a novel function of
      the enormous protocadherins in cerebellar development, namely, the modulation of
      the extracellular space surrounding parallel fibers during development, was
      proposed.

PMID- 12213441
TI  - Pak1 is involved in dendrite initiation as a downstream effector of Rac1 in
      cortical neurons.
AB  - Dendrite development in neurons is one of the bases for the formation of a
      complex neuronal network in the nervous system, and involvement of the Rho family
      GTPases, including Rac1, Cdc42, and RhoA, in dendrite formation has been
      demonstrated. One of the effectors of Rac1 and Cdc42, p21-activated kinase 1
      (Pak1), is abundant in the brain; however, the function of Pak1 in neurons
      remains unknown. In order to clarify the roles of Pak1 in neurons, we introduced
      mutant Pak1 into immature neurons by a novel gene transfer technique using in
      utero electroporation. Introduction of constitutive active (CA)-Pak1 led to
      increase the number of dendrites, whereas introduction of dominant negative (DN)
      Pak1 caused a reduction, and coexpression of CA-Rac1 and DN-Pak1 also resulted in
      a reduction in the number of dendrites. These results suggest that Pak1 regulates
      dendrite initiation as a downstream effector of Rac1.

PMID- 12213442
TI  - Transcriptional upregulation of SCG10 and CAP-23 is correlated with regeneration
      of the axons of peripheral and central neurons in vivo.
AB  - We have compared SCG10 and CAP-23 expression with that of GAP-43 during axonal
      regeneration in the peripheral and central nervous systems (PNS, CNS) of adult
      rats. SCG10, CAP-23, and GAP-43 mRNAs were strongly upregulated by motor and
      dorsal root ganglion (DRG) neurons following sciatic nerve crush, but not after
      dorsal rhizotomy. When the sciatic nerve was cut and ligated to prevent
      reinnervation of targets, expression of all three mRNAs was prolonged. Neurons in
      the thalamic reticular nucleus and deep cerebellar nuclei transiently upregulated
      these mRNAs after axotomy, and showed prolonged upregulation of all three
      molecules when regenerating axons into peripheral nerve grafts inserted into the
      thalamus of cerebellum. Neurons in the dorsal thalamus and cerebellar cortex
      showed poor regenerative capacity and most did not upregulate any of these mRNAs.
      Thus, in both PNS and CNS neurons, the transcription of SCG10, CAP-23, and GAP-43
      mRNAs is coregulated following axotomy and during regeneration. Signals from
      living peripheral nerve appear to maintain expression of all three mRNAs in
      regenerating neurons, and in PNS neurons downregulation correlates with target
      reinnervation. Thus, SCG10 and CAP-23, as well as GAP-43, are likely to be
      important neuronal determinants of regenerative ability.

PMID- 12213443
TI  - Developmental regulation of beta1 integrins during angiogenesis in the central
      nervous system.
AB  - We examined beta1 integrin expression during angiogenesis in the developing mouse
      CNS. Maturation of blood vessels was accompanied by three main events: (1) marked
      upregulation of beta1 integrin expression; (2) a switch in beta1 integrin
      expression, from alpha4 and alpha5 at postnatal day 1 to alpha1 and alpha6 in the
      adult; and (3) downregulation of fibronectin and upregulation of laminin
      expression. Thus, blood vessel maturation was associated with a developmental
      switch, from fibronectin-mediated signaling early in angiogenesis, to laminin
      mediated signaling at later stages. To investigate the potential role of alpha4
      and alpha5 integrins in angiogenesis, we developed a novel approach to purify
      endothelial cells from the CNS by selective adhesion to fibronectin. BrdU
      incorporation showed that fibronectin induced more endothelial cell proliferation
      than laminin, and antibody-blocking studies revealed that fibronectin mediated
      its effect via both alpha4 and alpha5 integrins. This work provides the first
      evidence that there is a developmental switch in the use of beta1 integrins
      during angiogenesis. Furthermore, it suggests that regulation of beta1 integrin
      and ECM expression by endothelial cells are important factors influencing
      vascular development in the CNS.

PMID- 12213444
TI  - In vivo neuronal tracing with GFP-TTC gene delivery.
AB  - The retrograde transport and transynaptic transfer properties of the nontoxic
      tetanus toxin C-fragment (TTC) can be used to visualize specific neural pathways
      or to deliver biomolecules in the central nervous system (CNS). Here we tested
      different delivery techniques to explore the potential use of a new GFP-TTC
      fusion construct for use as a genetic tracer in vivo. Plasmids encoding GFP-TTC
      were targeted to brain regions using intracerebral grafted transfected cells or
      adenoviral transduction. Transport was monitored using GFP fluorescence. We show
      that following GFP-TTC synthesis in grafted transfected cells, the TTC fragment
      alone, with no signal peptide, is necessary and sufficient to provide secretion
      and uptake of the fusion protein into neighboring neurons around the injection
      site. Using an adenoviral vector to express the fusion protein into brain
      neurons, we show that transduced neurons can deliver the fusion protein
      specifically into connected neurons, demonstrating that synaptic transfer in the
      CNS can be visualized with GFP-TTC.

PMID- 12213445
TI  - Abnormal phosphorylation of synapsin I predicts a neuronal transmission
      impairment in the R6/2 Huntington's disease transgenic mice.
AB  - Motor and cognitive deficits in Huntington's disease (HD) are likely caused by
      progressive neuronal dysfunction preceding neuronal cell death. Synapsin I is one
      of the major phosphoproteins regulating neurotransmitter release. We report here
      an abnormal phosphorylation state of synapsin I in the striatum and the cerebral
      cortex of R6/2 transgenic mice expressing the HD mutation. These changes are
      mostly characterized by an early overphosphorylation at sites 3-5, whereas
      phosphorylation at site 1 remains unchanged and at site 6 becomes reduced only
      close to the end stage of the disease. Such changes do not result from
      modification in protein expression levels. However, we show a decreased
      expression of the calcineurin regulatory subunit-B, which may contribute to an
      imbalance between kinase and phosphatase activities. Together the results suggest
      that an early impairment in synapsin phosphorylation-dephosphorylation may alter
      synaptic vesicle trafficking and lead to defective neurotransmission in HD.

PMID- 12213446
TI  - Dendritic localization of mammalian neuralized mRNA encoding a protein with
      transcription repression activities.
AB  - Drosophila neurogenic gene neuralized (neu) is required for the maintenance of
      neuroblast cell fate and differentiation. In the present study we have
      characterized a mouse and a rat homologue of Drosophila neu. Mammalian neu1
      encodes several C-terminal RING zinc finger proteins with one or two neuralized
      homology repeat (NHR) domains. Mammalian neu1 mRNAs are predominantly expressed
      in the nervous system and in the skeletal muscle with the highest levels in the
      adult. In the nervous system neu1 mRNAs are expressed in neurons and
      dendritically localized in several brain regions, suggesting a role of neu1 in
      the regulation of synaptic function. Mammalian neu1 isoforms exhibit
      transcription repression activities that are mediated by NHR domains and
      regulated by nucleocytoplasmic shuttling. In conclusion, our results suggest that
      mammalian neu1 is a protein with transcriptional repressor activities involved in
      the regulation of myo- and neurogenesis.

PMID- 12213447
TI  - Expression of the POU-domain transcription factors SCIP/Oct-6 and Brn-2 is
      associated with Schwann cell but not oligodendrocyte remyelination of the CNS.
AB  - The class III POU-domain transcription factor SCIP/Oct-6 is expressed by
      promyelinating Schwann cells and, in tissue culture, by oligodendrocyte
      progenitors (OPs), but is down-regulated in both cells types as they
      differentiate. Although the expression of SCIP/Oct-6 has been examined in
      peripheral nerve remyelination, its expression in CNS remyelination has not been
      addressed. Using a toxin model of demyelination, in which the demyelinated axons
      are remyelinated in an age-dependent manner by both oligodendrocytes and Schwann
      cells, we have compared the expression of SCIP/Oct-6 mRNA with that of an OP
      marker (PDGF-alphaR), a marker of myelinating oligodendrocytes (PLP), and markers
      of myelinating Schwann cells (P(0) and Krox-20) by in situ hybridization. We have
      found that the expression of SCIP/Oct-6 mRNA precedes that of P(0) and Krox-20
      mRNA expression, but bears little correlation with the expression profiles of
      either PDGF-alphaR or PLP mRNA. Moreover, there is a spatial correlation between
      the expression SCIP/Oct-6 mRNA and that of P(0) but not of PDGF-alphaR. These
      results indicate that SCIP/Oct-6 expression following CNS demyelination is
      associated with Schwann cell and not oligodendrocyte remyelination. We have also
      shown that another POU-domain transcription factor, Brn-2, is expressed during
      CNS remyelination, but that like SCIP/Oct-6, it too has an expression profile
      indicating that it is associated with the Schwann cell component of
      remyelination. In addition, we show that Brn-2 expression in Schwann cells is not
      restricted to CNS remyelination but is also expressed in a similar manner to
      SCIP/Oct-6 during Schwann cell myelination of neonatal peripheral nerves and
      regenerating transected adult nerve and in cultured Schwann cells following
      induction of elevated cAMP levels.

PMID- 12213448
TI  - A lysine residue in the beta3 subunit contributes to the regulation of GABA(A)
      receptor activity by voltage.
AB  - GABA(A) receptors (GABARs) are responsible for most fast inhibitory
      neurotransmission in the mammalian brain. The whole-cell currents of many native
      and recombinant GABARs exhibit outward rectification. This property has been
      shown to depend in part upon the identity of the alpha and beta subtype, but the
      structural determinants controlling this characteristic are not well known. An
      extracellular lysine residue conserved in the beta subunit family and located
      near the third transmembrane domain was examined. Mutations were made in the
      alpha1, beta3, and gamma2L subunits, exchanging the wild-type residue for either
      the lysine found in the beta subunit family or the threonine found in the alpha
      and gamma families. GABARs containing the mutated alpha1 or gamma2L subunits
      showed a large increase in outward rectification. Conversely, replacing the
      lysine in the beta3 subunit with threonine resulted in a nearly linear current
      voltage relationship and an increased sensitivity to GABA. Replacing this lysine
      with uncharged or negatively charged residues consistently eliminated outward
      rectification, with varying effects on GABA sensitivity. Similar mutations of the
      four other charged residues within the beta3 subunit M2-M3 domain did not alter
      rectification. These results suggest that lysine279 of the beta3 subunit plays an
      important role in the regulation of GABAR activity by membrane voltage.

PMID- 12213450
TI  - Mice deficient for the HNK-1 sulfotransferase show alterations in synaptic
      efficacy and spatial learning and memory.
AB  - The HNK-1 carbohydrate structure, a sulfated glucuronyl-lactosaminyl residue
      carried by many neural recognition molecules, is involved in cell interactions
      during ontogenetic development and in synaptic plasticity in the adult. To
      characterize the functional role of the HNK-1 carbohydrate in vivo, we have
      generated mice deficient for the HNK-1 sulfotransferase (ST). The ST-/- allele is
      inherited with Mendelian frequencies, and the ST-/- mice are viable and fertile.
      The anatomy of all major brain areas appeared histologically normal. However,
      basal synaptic transmission in pyramidal cells in the CA1 region of the
      hippocampus was increased and long-term potentiation evoked by theta-burst
      stimulation was reduced in ST mutants. In the water maze, ST-/- mice showed an
      impaired long-term memory and a poorer spatial learning when a short inter-trial
      interval was used. These observations indicate an essential role for the sulfate
      group of the HNK-1 carbohydrate in synaptic plasticity of the hippocampus.

PMID- 12213449
TI  - The alpha9/alpha10-containing nicotinic ACh receptor is directly modulated by
      opioid peptides, endomorphin-1, and dynorphin B, proposed efferent cotransmitters
      in the inner ear.
AB  - Opioid peptides have been detected in the auditory and vestibular efferent
      neurons where they colocalize with the major neurotransmitter, acetylcholine. We
      investigated the function of opioids to modulate neurotransmission mediated by
      hair cell's alpha9/alpha10-containing nicotinic acetylcholine receptors
      (alpha9/alpha10nAChRs). The endogenous opioid peptides, endomorphin-1 (mu
      agonist) and dynorphin B (kappa agonist), but not a delta agonist [D-Pen2,D-Pen
      5]enkephalin, inhibited the acetylcholine-evoked currents in frog saccular hair
      cells and rat inner hair cells. This inhibition was noncompetitive, voltage
      independent, and was accompanied by an acceleration of the rate of current decay.
      Selective mu- and kappa-opioid receptor antagonists did not block the inhibition,
      although partial reduction by naloxone was observed. All opioid antagonists
      tested also reduced the acetylcholine response. Endomorphin-1 and dynorphin B
      inhibited the acetylcholine-evoked currents in alpha9/alpha10-expressing Xenopus
      oocytes. Because oocytes lack opioid receptors, it provides strong evidence for
      the direct interaction of opioid peptides with alpha9/alpha10nAChR. CONCLUSION:
      alpha9/alpha10nAChR is a target for modulation by endomorphin-1 and dynorphin B,
      efferent cotransmitters in the inner ear.

PMID- 12213451
TI  - 5-Substituted-1H-tetrazoles as carboxylic acid isosteres: medicinal chemistry and
      synthetic methods.
AB  - 5-Substituted-1H-tetrazoles (RCN4H) are often used as metabolism-resistant
      isosteric replacements for carboxylic acids (RCO2H) in SAR-driven medicinal
      chemistry analogue syntheses. This review provides a brief summary of the
      medicinal chemistry of tetrazolic acids and highlights some examples of tetrazole
      containing drug substances in the current literature. A survey of representative
      literature procedures for the preparation of 5-substituted-1H-tetrazoles,
      focusing on preparations from aryl and alkyl nitriles, is presented in sections
      by generalized synthetic methods.

PMID- 12213452
TI  - Synthesis and biological evaluation of A-ring biaryl-carbamate analogues of
      rhazinilam.
AB  - An improvement of the synthesis of biphenyl-carbamate 2a, the most active
      analogue of rhazinilam 1 so far, was performed using the Pd-catalyzed
      borylation/Suzuki coupling (BSC) method developed in our laboratories. The
      preparation of A-ring analogues of 2a bearing electron-withdrawing or donating
      groups is reported according to this new synthetic scheme. The antitubulin
      properties as well as the cytotoxicity of these compounds toward human cancer
      cell lines were evaluated in comparison with rhazinilam and 2a.

PMID- 12213453
TI  - New dsDNA binding unnatural oligopeptides with pyrimidine selectivity.
AB  - Solid phase peptide library screening followed by extension of a lead recognition
      element for binding to a dsDNA sequence (NF binding site of IL6) using solution
      phase screening, delivered a new DNA binding peptide, Ac-Arg-Ual-Sar-Chi-Chi-Tal
      Arg-CONH2. In the present research, the contribution of the different amino acid
      side chains to the binding strength of the peptide to dsDNA was investigated
      using an ethidium bromide displacement test. Based on these results, the lead
      structure was optimized by deconvolution. Eight new unnatural amino acids were
      evaluated at two positions of the heptapeptide replacing the Ual-Sar fragment.
      The strongest dsDNA binding was observed using ([(3
      chlorophenyl)methyl]amino)acetic acid (Cbg) and beta-cyclohexyl-l-alanine (Cha)
      respectively, at those two positions. A 10-fold increase in affinity compared to
      the Ual-Sar sequence was obtained. Further enhancement of dsDNA binding was
      obtained with hybrid molecules linking the newly developed peptide fragment to an
      acridine derivative with a flexible spacer. This resulted in ligands with
      affinities in the microM range for the dsDNA target (K(d) of 2.1 x 10(-6) M).
      DNase I footprinting with the newly developed oligopeptide motifs showed the
      presence of a pronounced pyrimidine specificity, while conjugation to an
      intercalator seems to redirect the interaction to mixed sequences. This way, new
      unnatural oligopeptide motifs and hybrid molecules have been developed endowed
      with different sequence selectivities. The results demonstrate that the unnatural
      peptide library approach combined with subsequent modification of selected amino
      acid positions, is very suited for the discovery of novel sequence-specific dsDNA
      binding ligands.

PMID- 12213454
TI  - 1,4-Benzothiazine and 1,4-benzoxazine imidazole derivatives with antifungal
      activity: a docking study.
AB  - We have recently described the synthesis and antifungal activity of a series of
      1,4-benzothiazine and 1,4-benzoxazine imidazole derivatives that mainly showed in
      vivo activity against a murine experimental model of candidiasis but that very
      often lacked in vitro activity. Here, we report a docking study of a
      representative set of our molecules in a 3D model of CYP51 of Candida albicans
      (CA-CYP51). The model was constructed on the basis of the sequence homology
      relationship with the recently reported crystal structure of the CYP51 of
      Mycobacterium tuberculosis (MT- CYP51).

PMID- 12213455
TI  - The disaccharide anthracycline MEN 10755 binds human serum albumin to a non
      classical drug binding site.
AB  - The interaction of the novel disaccharide anthracycline MEN 10755 with human
      serum albumin (HSA) was investigated by visible absorption and fluorescence
      spectroscopies and by ultrafiltration. Notably, MEN 10755 binds serum albumin far
      stronger than doxorubicin. Albumin binding results into a drastic quenching of
      the intrinsic fluorescence of MEN 10755; a binding constant of 1.1 x 10(5) was
      determined from fluorescence data. To localize the HSA binding site of MEN 10755
      competition experiments were carried out with ligands that are selective for the
      different drug binding sites of the protein. No relevant competition effects were
      seen in the case of warfarin, diazepam and hemin, known ligands of sites I, II
      and III, respectively. Modest effects were observed following addition of
      palmitic acid that targets the several fatty acid binding sites of the protein.
      In contrast, extensive displacement of the bound anthracycline was achieved upon
      addition of ethacrinic acid. On the basis of these results, it is proposed that
      MEN 10755 binds serum albumin tightly to a non-canonical surface binding site for
      which it competes specifically with ethacrinic acid.

PMID- 12213456
TI  - Xanthones as inhibitors of microsomal lipid peroxidation and TNF-alpha induced
      ICAM-1 expression on human umbilical vein endothelial cells (HUVECs).
AB  - Xanthones bearing different functionalities, namely 1-hydroxyxanthone (1), 3
      hydroxyxanthone (2), 1,4-dihydroxyxanthone (3), 2,6-dihydroxyxanthone (4), 1,2
      diacetoxyxanthone (5), 2,6-diacetoxyxanthone (6), 3-methoxyxanthone (7), 1,3,7
      trimethoxyxanthone (8) and 1,5-dihydroxy-6-methoxyxanthone (9) were synthesised
      and examined for their effect on nicotinamide adenine dinucleotide phosphate
      (NADPH)-catalysed liver microsomal lipid peroxidation and on tumour necrosis
      factor-alpha (TNF-alpha) induced expression of intercellular adhesion moledule-1
      (ICAM-1) on endothelial cells, with a view to establish structure-activity
      relationship. Hydroxy- and acetoxyxanthones showed potent inhibitory effects on
      NADPH-catalysed lipid peroxidation and TNF-alpha induced expression of ICAM-1 on
      endothelial cells.

PMID- 12213457
TI  - A convenient synthetic method of a 5,7-diarylcyclopenteno-[1,2-b]pyridine-6
      carboxylate: a key intermediate for potent endothelin receptor antagonists.
AB  - A convenient method for the synthesis of the title intermediate 4 was described.
      The key steps of this synthesis involved: (1) regioselective addition reaction of
      arylzinc reagent to quinolic anhydride in 42% isolated yield, (2) conversion of a
      ketoacid to an enone, which was achieved in 65% yield by intramolecular
      Knoevenagel reaction of beta-ketoester generated by condensation of an acid
      imidazolide with an ester enolate, followed by dehydration assisted with silica
      gel, and (3) stereoselective reduction of an allyl alcohol in 75% yield with zinc
      under acidic conditions. This synthesis enabled us to provide hundreds of grams
      of without chromatographic purification.

PMID- 12213458
TI  - Halohydrin and oxime derivatives of radicicol: synthesis and antitumor
      activities.
AB  - Novel halohydrin and oxime derivatives of radicicol (1) were prepared and
      evaluated for their v-src tyrosine kinase inhibitory, antiproliferative, and
      antitumor activities. Some of the resulting derivatives showed significantly
      improved antitumor activities than those of 1 in vitro as tested in a cell
      proliferation assay and in vivo using sc-inoculated human breast carcinoma and
      epidermoid tumor models. Design and synthesis of radicicol-based novel affinity
      probes are also described.

PMID- 12213459
TI  - Synthesis of 17beta-N-substituted 19-Nor-10-azasteroids as inhibitors of human
      5alpha-reductases I and II.
AB  - The synthesis of 17beta-[N-(phenyl)methyl/phenyl-amido] substituted 10
      azasteroids has been accomplished by either the TiCl4- or TMSOTf-catalysed
      reaction of carbamates 11 and 12 with Danishefsky's diene. The reaction provided
      5alpha-H isomers 3a-5a and 5beta-H isomers 3b-5b depending on the reaction
      conditions. Both epimers of each compound were tested against human 5alpha
      reductase types I and II. Unexpectedly, 5beta-H compounds were found more active
      than their 5alpha-H counterparts, the best inhibitors being 3b (IC50=279 and 2000
      nM toward isoenzyme I and II, respectively) and 5b (IC50=913 and 247 nM toward
      isoenzymes I and II, respectively).

PMID- 12213460
TI  - Hemi-synthesis and biological activity of new analogues of podophyllotoxin.
AB  - Various 4-analogues of podophyllotoxin and epipodophyllotoxin were obtained via
      the formation of the corresponding 4-keto derivatives. Methyloximation of
      podophyllotoxone, followed by subsequent catalytic hydrogenation, gave
      stereoselective access to 4-alpha-amino-4-deoxypodophyllotoxin and from there, to
      the corresponding acetamido and formamido derivatives. Base-catalyzed
      isomerisation of 4-alpha-amino-4-deoxypodophyllotoxin led to the corresponding
      picropodophyllin isomer while the 4-beta-amino afforded a neopodophyllotoxin-like
      derivative. On the other hand, oxirane and hydroxymethyl-containing analogues
      were prepared from podophyllotoxin and 4-epi-4'-demethyl-podophyllotoxin, using a
      Takai olefination strategy. In the latter series, carboxaldehyde- and carboxylic
      acid-containing derivatives were also synthesized.

PMID- 12213461
TI  - Synthesis and structure-activity relationship of diarylamide derivatives as
      selective inhibitors of the proliferation of human endothelial cells.
AB  - A series of diarylamide urea derivatives were synthesized and evaluated for their
      inhibitory activities against human coronary artery endothelial cells (ECs) and
      human coronary artery smooth muscle cells (SMCs). Compound was superior to
      Tranilast, in terms of both cell selectivity and the potency of its inhibitory
      activity toward the proliferation and angiogenesis of ECs.

PMID- 12213462
TI  - Antitumor agents. Part 214: synthesis and evaluation of curcumin analogues as
      cytotoxic agents.
AB  - Fifty-eight curcumin analogues were prepared and evaluated for in vitro
      cytotoxicity against a panel of human tumor cell lines. Compound was the most
      potent analogue against several cell lines, including HOS (bone cancer) and 1A9
      (breast cancer), with ED50 values of 0.97 and <0.63 microg/mL, respectively.

PMID- 12213463
TI  - Design, synthesis, and biological evaluation of a series of beta-lactam-based
      prodrugs.
AB  - By use of pro-dual-drug concept the synthesis of 6-beta-[(R)-2-(clavaminio-9-N
      yl)-2-(4-hydroxyphenylacetamido)]penicillanic acid (10), 6-beta-[(R)-2-(amino)-2
      (4-(clavulano-9-O-yl)phenylacetamido)]penicillanic acid (13), (Z)-4-[2
      (amoxycillin-4-O-yl)ethylidene]-2-(clavulano-9-O-yl)-3-methoxy-Delta(alpha,beta)
      butenolide (19), and 3-[(amoxicillin-4-O-yl)methyl]-7-(phenoxyacetamido)-(1-oxo)
      3-cephem-4-carboxylic acid (23) was accomplished. Unlike penicillin G,
      ampicillin, or amoxicillin, these four heretofore undescribed compounds 10, 13,
      19, and 23 showed notable activity against beta-lactamase (betaL) producing
      microorganisms, Staphylococcus aureus A9606, S. aureus A15091, S. aureus A20309,
      S. aureus 95, Escherichia coli A9675, E. coli A21223, E. coli 27C7, Pseudomonas
      aeruginosa 18S-H, and Klebsiella pneumoniae A20634 TEM. In comparison with
      amoxicillin (9), alpha-amino-substituted compound 10 and butenolide derivative 19
      showed a broadened spectrum of antibacterial activity; yet they were found to be
      less active than 13 and 23. Like clavulanic acid (7) or cephalosporin-1-oxide
      (21), the newly synthesized compounds 10, 13, 15, 16, 19, or 23 functioned as
      potent inhibitors of various bacterial betaLs.

PMID- 12213464
TI  - Prediction of lipophilicity of polyacenes using quantitative structure-activity
      relationships.
AB  - Predictive models for the lipophilicity (logP) of first 25 derivatives of
      polyacenes are reported. The models are derived from distance-based numerical
      descriptors which encode information about topology of each compounds in the data
      set. A new PI-type index called Sadhna index and abbreviated as Sd is introduced
      for the first time, and its relative correlation potential is established using
      the results obtained from Wiener (W), Szeged (Sz), first-order Randic
      connectivity (chi), and Padmakar-Ivan indices. The data show that lipophilicity
      (logP) is best modelled in bi-parametric model containing PI and Sd indices. The
      effect due to size, shape, branching, steric and polarity effects on the
      exhibition of lipophilicity is critically discussed. The predictive ability of
      the models is discussed on the basis of cross-validation parameters.

PMID- 12213465
TI  - Methylation of L-trans-2,4-pyrrolidine dicarboxylate converts the glutamate
      transport inhibitor from a substrate to a non-substrate inhibitor.
AB  - The 4-methyl analogue of the potent inhibitor of CNS L-glutamate neurotransmitter
      transporters, L-trans-2,4-PDC, was synthesized via a 1,3-dipolar cycloaddition
      reaction sequence. The bioassays performed not only exhibit increased potency of
      the methylated derivative over L-trans-2,4-PDC, but also exhibit non-substrate
      properties at the rat forebrain synaptosomal glutamate transporter while the
      parent L-trans-2,4-PDC exhibits substrate properties. These results support two
      hypotheses developed for distinguishing the physiological properties of transport
      inhibitors based on molecular modeling studies, and are reported here.

PMID- 12213466
TI  - QSAR study on narcotic mechanism of action and toxicity: a molecular connectivity
      approach to Vibrio fischeri toxicity testing.
AB  - Quantitative structure-activity relationships (QSARs) have been established based
      on narcotic mechanism of action and toxicity data to Vibrio fischeri using
      molecular connectivity indices. The results obtained suggest that both, the
      degree of branching and electronic characteristic of the compounds have dominant
      role in the exhibition of toxicity. The information obtained in the present study
      will be useful in designing more potent compounds.

PMID- 12213467
TI  - Tc and Re chelates of 8alpha-amino-6-methyl-ergoline: synthesis and affinity to
      the dopamine D2 receptor.
AB  - The influence of structural changes at the 8alpha-amino position of 8alpha-amino
      6-methyl-ergoline on the lipophilicity and affinity to the D2 receptor was
      studied. 8alpha-amino-6-methyl-ergoline (1) was converted into the derivatives
      (2a-f) by mercaptoacetylation of the amino group to make it possible to prepare
      the rhenium and technetium complexes (3, 4a,b). Binding tests on cloned human
      dopamine D2 receptors show that the affinities of the coordination compounds
      (IC50 values between 50 and 240 nM) are less than those of the derivatives 2a-f
      (IC50=3-50 nM) but more than those of the parent compound 1. Biodistribution
      studies of the Tc complexes 4a,b performed on Wistar rats show a slow blood
      clearance with substantial accumulation and retention in the liver and kidneys
      and low brain uptake.

PMID- 12213468
TI  - Tetrahydroisoquinoline-3-carboxylate based matrix-metalloproteinase inhibitors:
      design, synthesis and structure-activity relationship.
AB  - The design, synthesis and structure-activity relationship (SAR) of a series of
      nonpeptidic 2-arylsulfonyl-1,2,3,4-tetrahydro-isoquinoline-3-carboxylates and
      hydroxamates as inhibitors of the matrix metalloproteinase human neutrophil
      collagenase (MMP-8) is described here. Based on available X-ray structures of MMP
      8/inhibitor complexes, our structure-based design strategy was directed to
      complement major protein-ligand interaction regions mainly in the S1' hydrophobic
      specificity pocket close to the catalytic zinc ion. Here, the rigid 1,2,3,4
      tetrahydroisoquinoline scaffold (Tic) provides ideal geometry to combine
      hydroxamates and carboxylates as typical zinc complexing functionalities, with a
      broad variety of S1' directed mono- and biaryl substituents consisting of
      aromatic rings perfectly accommodated within this more hydrophobic region of the
      MMP-8 inhibitor binding site. The effect of different S1' directed substituents,
      zinc-complexing groups, chirality and variations of the tetrahydroisoquinoline
      ring-system is investigated by systematic studies. X-ray structure analyses in
      combination with 3D-QSAR studies provided an additional understanding of key
      determinants for MMP-8 affinity in this series. The hypothetical binding mode for
      a typical molecule as basis for our inhibitor design was found in good agreement
      with a 1.7 A X-ray structure of this candidate in complex with the catalytic
      domain of human MMP-8. After analysis of all systematic variations, 3D-QSAR and X
      ray structure analysis, novel S1' directed substituents were designed and
      synthesized and biologically evaluated. This finally results in inhibitors, which
      do not only show high biological affinity for MMP-8, but also exhibit good oral
      bioavailability in several animal species.

PMID- 12213469
TI  - Highly-iodinated fullerene as a contrast agent for X-ray imaging.
AB  - The first fullerene-based X-ray contrast agent (CA) has been designed,
      synthesized, and characterized. The new CA is an externally functionalized
      derivative of C60 that is conceptually based on contemporary X-ray CA, all of
      which use iodine as the X-ray attenuating vehicle and are based on the 2,4,6
      triiodinated-benzene-ring substructure. Using a modified Bingel-type reaction, a
      single addend containing 6 iodine atoms and 8 protected hydroxyl groups was
      appended to C60 followed by the addition of 4 more addends each containing 4
      protected hydroxyl groups. Final deprotection afforded the highly water-soluble
      (>460 mg/mL), non-ionic, highly-iodinated (24% I) fullerene for application as an
      X-ray contrast agent.

PMID- 12213470
TI  - Development of a purine-scaffold novel class of Hsp90 binders that inhibit the
      proliferation of cancer cells and induce the degradation of Her2 tyrosine kinase.
AB  - The first published synthesis and characterization of a purine-scaffold library
      of hsp90 inhibitors is presented. The purine-scaffold represents a platform for
      the creation of easily synthesizable and derivatizable soluble molecules that are
      amenable for oral administration. The most active compound of the series (71)
      exhibits binding to hsp90 comparable to the natural product derivative 17AAG that
      is now in Phase I clinical trial as a cancer therapeutic. Induces the degradation
      of Her2 tyrosine kinase and arrests the MCF-7 breast cancer cell line at low
      micromolar concentrations (IC50=2 microM).

PMID- 12213471
TI  - Synthesis of (-)-5,8-dihydroxy-3R-methyl-2R-(dipropylamino)-1,2,3,4
      tetrahydronaphthalene: an inhibitor of beta-amyloid(1-42) aggregation.
AB  - A concise synthesis of the beta-amyloid(1-42 )aggregation inhibitor (-)-5,8
      dihydroxy-3R-methyl-2R-(dipropylamino)-1,2,3,4-tetrahydronaphthalene [(-)-2] has
      been developed. The key step is a regio- and diastereoselective hydroboration
      amination sequence to convert alkene into amine. Enantiomeric resolution was
      achieved by recrystallization of amine as the dibenzoyl-D-tartaric acid salt.
      Hydroquinone is a potent inhibitor of the fibrillar aggregation of beta-amyloid
      as determined in two different assay systems.

PMID- 12213472
TI  - Quantitative structure-activity relationship studies on 5-phenyl-3-ureido-1,5
      benzodiazepine as cholecystokinin-A receptor antagonists.
AB  - Quantitative structure-activity relationship (QSAR) studies on a series of 5
      phenyl-3-ureido-1,5-benzodiazepine-2,4-diones has been carried out using a pool
      of distance-based topological indices. Step-wise regression analysis indicated
      that penta-parametric regression expression containing Sz, B, Ip1, Ip2 and Ip3 is
      the most potent and selective for CCK-A affinity. The predictive potential of the
      model is discussed on the basis of cross-validation parameters as well as by
      estimating root mean square (RMSR) of the residuals.

PMID- 12213473
TI  - Design and synthesis of an irreversible dopamine-sparing cocaine antagonist.
AB  - Cocaine is a powerful reinforcer and stimulant that binds to specific recognition
      sites associated with monoamine transporters in the mammalian brain. The search
      for a functional antagonist to the addictive properties of cocaine has focused on
      the discovery of a molecule that can inhibit cocaine binding to the dopamine
      transporter (DAT) but continue to allow dopamine transport by the DAT. No such
      dopamine-sparing cocaine antagonist has been reported and it is becoming evident
      that dopamine-sparing antagonism of the pharmacological effects of cocaine by a
      classical antagonist may not be possible. Herein we present a new concept for the
      design of dopamine-sparing cocaine antagonists. A unique approach is utilized to
      deliver an inhibitor that binds irreversibly to the DAT, then cleaves and leaves
      behind a small fragment attached to the DAT that blocks access by cocaine but
      permits dopamine transport. The design of these compounds takes advantage of a
      cysteinyl sulfhydryl group in the DAT. This group is hypothesized to attack the
      incoming inhibitor and lead to selective inhibition of the cocaine binding site
      while sparing dopamine transport. This concept of a mechanism based irreversible
      dopamine-sparing cocaine antagonist has now been demonstrated to be viable and,
      as example, the unsaturated 6 showed inhibition of cocaine (63%) at the DAT after
      24h incubation, while at that point considerably less inhibition of dopamine is
      manifested (23%). In contrast, the epoxide 7 showed a greater inhibition of
      dopamine reuptake than cocaine binding at 24h (68% versus 18%).

PMID- 12213474
TI  - Determination of the phamacophore of penclomedine, a clinically-evaluated
      antitumor pyridine derivative.
AB  - The main objective of this investigation was to identify the reactive
      pharmacophore in penclomedine (PEN, 3,5-dichloro-4,6-dimethoxy-2
      (trichloromethyl) pyridine) for in vivo antitumor activity and also to discover
      related ring structures and sulfur analogues that might exhibit superior
      antitumor activity in vivo. Several new analogues of PEN and related structural
      variants have been synthesized and evaluated in vivo against MX-1 human breast
      tumor xenograft implanted subcutaneously (sc), although none of them demonstrated
      significant activity.

PMID- 12213475
TI  - A structure-activity study of spermicidal and anti-HIV properties of hydroxylated
      cationic surfactants.
AB  - The syntheses of 2-hydroxy-N-(2-hydroxyethyl)-N,N-dimethylhexadecan-1-aminium
      chloride [1(16)Cl] and iodide [1(16)I], 2-hydroxy-N,N,N-trimethylhexadecan-1
      aminium chloride (6), N-(2-hydroxyethyl)-N,N-dimethylhexadecan-1-aminium chloride
      (8), N,N-bis(2-hydroxyethyl)-N-methylhexadecan-1-aminium chloride (11), and 2
      hydroxy-N-(2-hydroxyethyl)-N,N-dimethyl-4-oxahexadecan-1-aminium chloride (14)
      are reported along with the critical micelle concentrations (cmcs), as measured
      by conductivity at 25 degrees C, of 1(16)Cl, 1(16)I, 6, 8, 11, and N,N,N
      trimethylhexadecan-1-aminium chloride (12). All compounds display spermicidal and
      virucidal activity. A plot of minimum effective concentration (MEC) in the Sander
      Cramer spermicidal assay and cmc shows that 1(16)Cl and 6 have the best
      spermicidal activity and highest cmcs. Compounds 8, 11, and 1(16)Cl are the most
      active at 0.05 mg mL(-1) against cell-free and cell-associated virus. In
      conclusion, 1(16)Cl shows the best combination of dual activity against sperm and
      HIV; it is a promising candidate for further preclinical studies as a topical,
      contraceptive microbicide.

PMID- 12213476
TI  - Novel branching membrane translocational peptide as gene delivery vector.
AB  - A fragment of HIV-tat protein, RKKRRQRRR, has been shown to have membrane
      penetration and nuclear localization properties, which are critical attributes of
      gene therapy agents. In this study, we designed a series of arborizing tat
      peptides, containing 1-8 tat moieties, and evaluated them as transfection
      enhancers in a variety of cell lines. We found that all compounds complexed with
      plasmid DNA, but only the molecule containing 8 tat-peptide chains shows
      significant transfection capabilities. Using rhodamine labeled plasmid and eight
      tat-peptide complex, we were also able to demonstrate intracellular delivery of
      the complex by fluorescence microscopy.

PMID- 12213477
TI  - Inhibition of inosine monophosphate dehydrogenase (IMPDH) by the antiviral
      compound, 2-vinylinosine monophosphate.
AB  - A new enzyme-mediated synthesis of 2-vinylinosine, a compound with broad-spectrum
      RNA antiviral activity, is described. In order to understand the mechanism of
      action of this compound, we synthesized its monophosphate and investigated the
      behavior of that compound toward the enzyme, inosine monophosphate dehydrogenase
      (IMPDH), a key enzyme involved in the biosynthesis of nucleotides. 2-Vinylinosine
      monophosphate is a potent inhibitor of IMPDH with a K(i) of 3.98 microM
      (k(inact)=2.94 x 10(-2) s(-1)). The antiviral activity of 2-vinylinosine may be
      explained by its cellular conversion to the monophosphate through the sequential
      action of PNP and HGPRT and subsequent inhibition of IMPDH by the cellularly
      produced 2-vinylinosine 5'-monophosphate.

PMID- 12213478
TI  - Thalassiolins A-C: new marine-derived inhibitors of HIV cDNA integrase.
AB  - Human immunodeficiency virus (HIV) replication requires integration of viral cDNA
      into the host genome, a process mediated by the viral enzyme integrase. We
      describe a new series of HIV integrase inhibitors, thalassiolins A-C (1-3),
      isolated from the Caribbean sea grass Thalassia testudinum. The thalassiolins are
      distinguished from other flavones previously studied by the substitution of a
      sulfated beta-D-glucose at the 7-position, a substituent that imparts increased
      potency against integrase in biochemical assays. The most active of these
      molecules, thalassiolin A (1), displays in vitro inhibition of the integrase
      catalyzed strand transfer reaction (IC50=0.4 microM) and an antiviral IC50 of 30
      microM. Molecular modeling studies indicate a favorable binding mode is probable
      at the catalytic core domain of HIV-1 integrase.

PMID- 12213479
TI  - Phospholipid-bound molecular rotors: synthesis and characterization.
AB  - Molecular rotors are fluorescent molecules with a viscosity-sensitive quantum
      yield that are often used to measure viscosity changes in cell membranes and
      liposomes. However, commercially available molecular rotors, such as DCVJ (1) do
      not localize in cell membranes but rapidly migrate into the cytoplasm leading to
      unreliable measurements of cell membrane viscosity. To overcome this problem, we
      synthesized molecular rotors covalently attached to a phospholipid scaffold.
      Attaching the rotor group to the hydrophobic end of phosphatidylcholine (PC) did
      not affect the rotor's viscosity sensitivity and allowed adequate integration
      into artificial bilayers as well as complete localization in the plasma membrane
      of an endothelial cell line. Moreover, these new rotors enabled the monitoring of
      phospholipid transition temperature. However, attachment of the rotor groups to
      the hydrophilic head of the phospholipid led to a partial loss of viscosity
      sensitivity. The improved sensitivity and exclusive localization in the cell
      plasma membrane exhibited by the phospholipid-bound molecular rotors suggest that
      these probes can be used for the study of membrane microviscosity.

PMID- 12213480
TI  - Synthesis and physical characterization of a P1 arginine combinatorial library,
      and its application to the determination of the substrate specificity of serine
      peptidases.
AB  - Serine peptidases are a large, well-studied, and medically important class of
      peptidases. Despite the attention these enzymes have received, details concerning
      the substrate specificity of even some of the best known enzymes in this class
      are lacking. One approach to rapidly characterizing substrate specificity for
      peptidases is the use of positional scanning combinatorial substrate libraries.
      We recently synthesized such a library for enzymes with a preference for arginine
      at P1 and demonstrated the use of this library with thrombin (Edwards et al.
      Bioorg. Med. Chem. Lett. 2000, 10, 2291). In the present work, we extend these
      studies by demonstrating good agreement between the theroretical and measured
      content of portions of this library and by showing that the library permits rapid
      characterization of the substrate specificity of additional SA clan serine
      peptidases including factor Xa, tryptase, and trypsin. These results were
      consistent both with cleavage sites in natural substrates and cleavage of
      commercially available synthetic substrates. We also demonstrate that pH or salt
      concentration have a quantitative effect on the rate of cleavage of the pooled
      library substrates but that correct prediction of optimal substrates for the
      enzymes studied appeared to be independent of these parameters. These studies
      provide new substrate specificity data on an important class of peptidases and
      are the first to provide physical characterization of a peptidase substrate
      library.

PMID- 12213481
TI  - Novel and potent anti-malarial agents.
AB  - Readily accessible, novel, and potent anti-malarial compounds have been
      developed. Optimization of the initial lead structure resulted in derivatives
      with IC50 values from 7 to 35 nM against chloroquine-sensitive and 70-350 nM
      against chloroquine-resistant strains of Plasmodium falciparum.

PMID- 12213482
TI  - Footprinting and circular dichroism studies on paromomycin binding to the
      packaging region of human immunodeficiency virus type-1.
AB  - We have studied the interaction of the aminoglycoside drug, paromomycin, with a
      171-mer from the packaging region of HIV-1 (psi-RNA), using quantitative
      footprinting and circular dichroism spectroscopy. The footprinting
      autoradiographic data were obtained by cutting end-labeled RNA with RNase I or
      RNase T1 in the presence of varying paromomycin concentrations. Scanning the
      autoradiograms produced footprinting plots showing cleavage intensities for
      specific sites on the psi-RNA as functions of drug concentration. Footprinting
      plots showing binding were analyzed using a two-state model to give apparent
      binding constants for specific sites of the psi-RNA. These plots show that the
      highest-affinity paromomycin binding site involves nucleotides near bulges in the
      main stem and SL-1, and other nucleotides in SL-4 of the psi-RNA. RNase I gives
      an apparent value of K for this drug site of approximately 1.7 x 10(5) M(-1)
      while RNase T1 reports a value of K of approximately 8 x 10(4) M(-1) (10 mM Tris
      HCl, pH 7). Footprinting shows that loading the highest affinity site with
      paromomycin causes structural changes in the single-stranded linker regions,
      between the stem-loops and main stem and the loops of SL-1 and SL-3. Drug-induced
      structural changes also affect the intensity of the 208 nm band in the circular
      dichroism spectrum of the psi-RNA. Fitting the changes in CD band intensity to a
      two-state model yielded a binding constant for the highest-affinity drug site of
      6 x 10(6) M(-1). Thus, the binding constants from footprinting are lower than
      those obtained for the highest-affinity site from the circular dichroism
      spectrum, and lower than those earlier obtained using absorption spectroscopy
      (Sullivan, J. M.; Goodisman, J.; Dabrowiak, J. C., Bioorg. Med. Chem. Lett. 2002,
      12, 615). The discrepancy may be due to competitive binding between drug and
      cleavage agent in the footprinting experiments, but other explanations are
      discussed. In addition to revealing sites of binding and regions of drug-induced
      structural change, footprinting showed that the loop regions of SL-1, SL-3 and SL
      4 are exposed in the RNA, whereas the linker region between SL-1 and SL-2 is
      'buried' and not accessible to cutting by RNase I or RNase T1.

PMID- 12213483
TI  - A convergent synthesis of core 2 branched sialylated and sulfated
      oligosaccharides.
AB  - A convergent pathway for the syntheses of core 2 oligosaccharide analogues 1 and
      2, and a natural form sialylated and sulfated hexasaccharide 3 was developed.
      Construction of pentasaccharides 24, 27 and hexasaccharide 28 was achieved by
      complete regioselective glycosylation of the 6-OH in the acceptors 5, 7 and 8,
      respectively, owing to the much higher reactivity of the primary hydroxyl group
      over the secondary axial hydroxyl group in these structures. Stereoselective
      sialylation was accomplished using donor 10 with defined configuration
      established through X-ray crystallographic analysis. Target oligosaccharides 1-3
      were then obtained by the systematic deprotection of intermediates 24, 27 and 29.
      With these target oligosaccharides 1-3 obtained, biological evaluations of these
      molecules as enzyme substrates was undertaken and selectin binding studies are
      planned.

PMID- 12213484
TI  - Novel peptidomimics as angiotensin-converting enzyme inhibitors: a combinatorial
      approach.
AB  - One of the efficient mode of treatments of chronic hypertension and
      cardiovascular disorders has been to restrain the formation of angiotensin-II by
      inhibiting the action of angiotensin-converting enzyme (ACE) on angiotensin-I. A
      number of ACE inhibitors (ACEIs) have been put to therapeutic use during the last
      two decades. The efforts continue towards achieving superior molecules or drugs
      with improved affinities, better bioavailability and thus long duration of action
      with minimum side effects. The present work evolves around similar objectives. In
      order to understand the mode of interaction of inhibitors with the active site of
      the enzyme and subsequently to have lead compounds as possible inhibitors the
      novel dipeptidomimics and tripeptidomimics have been designed and synthesized
      using combinatorial chemistry approach. A Focussed library of 10 di- and tri
      peptides, eight dipeptidomemics and forty tripeptidomemics was generated. The
      pharmacophoric heterocyclic moieties and the amino acids have been selected to
      have affinities with the S1, S1', and S2' subsites of the active site of the
      enzyme. ACE inhibition studies clearly demonstrated the structural-activity
      relationships within these classes of peptidomimics. The dipeptidomimics
      interacted only with S1' and S2' subsites, whereas the tripeptidomemics had
      additional interaction with S1 subsite, which accounted for their significant ACE
      inhibition potencies. The in-vitro screening of these peptidomimics have resulted
      in identification of four promising tripeptidomimics 34[2-benzimidazolepropionyl
      Val-Trp], 35[5hydroxytryptophanyl-Val-Trp], 40[2-benzimidazolepropionyl-Ile-Trp]
      and 45[2-benzimidazolepropionyl-Lys-Trp] with IC50 values in micromolar
      concentrations.

PMID- 12213487
TI  - Down-modulation of nuclear localisation and pro-fibrogenic effect of 4-hydroxy
      2,3-nonenal by thiol- and carbonyl-reagents.
AB  - Among the oxidative breakdown products of omega-6 unsaturated fatty acids, the
      aldehyde 4-hydroxy-2,3-nonenal (HNE) is receiving increasing attention for its
      potential pathophysiological implication, which at least partly lies on the
      demonstrated ability to modulate gene expression of a number of genes. Here we
      show that a marked down-modulation of HNE nuclear localisation in cells of a
      macrophage line (J774-A1) can be afforded by treatment with sulfydryl and
      carbonyl reagents without significantly interfering with cell viability. As
      regards the addition of thiol-group reagents to the cell suspension, N
      ethylmaleimide (NEM) led to a sustained decrease of HNE nuclear localisation,
      while 4-(chloromercuri)-benzene-sulfonic acid (PCMBS) gave a similar but more
      transient effect. Hydroxylamine (HYD), a carbonyl-group reagent, was also able to
      inhibit HNE nuclear localisation. The actual efficacy of the inhibitors used was
      then tested on the HNE-induced stimulation of transforming growth factor beta1
      (TGFbeta1) production by J774-A1 cells. Indeed, the thiol reagents NEM and PCMBS,
      both markedly down-modulating HNE nuclear localisation, were able to inhibit HNE
      induced increase of TGFbeta1 protein synthesis. The carbonyl reagent HYD was less
      effective on this respect, producing strong but incomplete protection against HNE
      induced TGFbeta1 increase. Taken together, the results indicate that sulfydryl
      groups are involved in the process of HNE cellular internalisation, while both
      sulfydryl and carbonyl groups are involved in the process of HNE nuclear
      translocation, and consequently in the modulation of gene expression by the
      aldehyde. Further, an actual demonstration is provided that HNE-induced effect on
      gene regulation can be efficiently counteracted by suitable interference with HNE
      biochemistry.

PMID- 12213488
TI  - Comparison of the stabilities and unfolding pathways of human apolipoprotein E
      isoforms by differential scanning calorimetry and circular dichroism.
AB  - Differential scanning calorimetry and circular dichroism experiments were
      performed to study structural differences among the common isoforms of human
      apolipoprotein E (apoE2, apoE3, and apoE4) and their N-terminal, 22-kDa
      fragments. Here, we examine thermodynamic properties that characterize the
      structural differences among isoforms, and also differences in their unfolding
      behavior. The 22-kDa fragments and their full-length counterparts were found to
      exhibit similar differences in thermal stability (apoE4<apoE3<apoE2; T(max)
      approximately 52<56<59 degrees C, respectively). Helical contents at the onset
      and completion of denaturation (as monitored calorimetrically) were about 51% and
      35%, respectively, for 22-kDa apoE3. As much as 70% of the unfolding enthalpy for
      22-kDa apoE3 could be due to disruption of alpha-helix. The monomeric 22-kDa
      fragments unfold differently, with both apoE3 and apoE4 exhibiting unfolding
      intermediates, whereas apoE2 unfolds according to a two-state mechanism.
      Interactions with the C-terminal domain appear to destabilize the N-terminal
      domains in full-length apoE2 and apoE3, but less so for full-length apoE4. Self
      association of full-length apoE at higher concentrations (1.5-2.5 mg/ml), as well
      as interaction of full-length apoE with phospholipid, enhances thermal stability.
      Cooperative changes in secondary structure, as monitored by circular dichroism,
      begin near 37 degrees C for full-length apoE3 and apoE4, indicating that full
      length apoE3 and apoE4, but not apoE2, may be partially unfolded in vivo. The
      differences in stability and unfolding behavior are likely to contribute to the
      molecular basis for defects in lipid transport and neurological function induced
      by apoE polymorphism.

PMID- 12213489
TI  - Spermine increases phosphatidylinositol 4,5-bisphosphate content in permeabilized
      and nonpermeabilized HL60 cells.
AB  - The polyamine spermine (N,N'bis[3-aminopropyl]-1,4-butanediamine) activates
      phosphatidylinositol-4-phosphate 5-kinase (PtdIns(4)P5K) and phosphatidylinositol
      4-kinase (PtdIns4K) in vitro. Spermine concentration increases that occur in
      proliferating cells were approximated in streptolysin O-permeabilized HL60 cells.
      When phospholipase C was activated by GTPgammaS in the presence of PITPalpha, 0.1
      1.2 mM spermine evoked increases in PtdIns(4,5)P(2) contents in a dose-dependent
      manner to 110-170% of control and concomitantly decreased inositol phosphate
      formation by 10-50%. Spermine-induced increases in PtdIns(4,5)P(2) content in
      permeabilized cells also occurred during GTPgammaS stimulation in the absence of
      PITPalpha, were augmented in the presence of PITPalpha, occurred in unstimulated
      cells and were additive to PtdIns(4,5)P(2) formation evoked by ARF1, another
      activator of phosphoinositide kinases. Slowly developing spermine-evoked
      increases in PtdIns(4,5)P(2) contents occurred in nonpermeabilized cells that
      were abolished in the presence of a spermine transport inhibitor. Data are
      consistent with spermine at physiological concentrations evoking a PITPalpha
      dependent shift in formation of PtdIns(4,5)P(2) from compartments that contained
      an active phospholipase C to compartments that were separated from an active PLC
      and from PtdIns(4,5)P(2) formed by ARF1.

PMID- 12213490
TI  - Active-dimeric form of lipoprotein lipase increases in the adipose tissue of
      patients with rheumatoid arthritis treated with prednisolone.
AB  - The synthesis, activity and mass of LPL in adipose tissue were studied in
      patients with rheumatoid arthritis (RA) treated with prednisolone (PSL) (PSL
      treated group) and untreated patients with osteoarthritis (untreated group). LPL
      activity and mass in the extracts of acetone/ether powder of adipose tissue were
      2.4 and 1.6 times, respectively, higher in the PSL-treated group than in the
      untreated group. There were no differences in the amount of 35S incorporated into
      LPL during the 2-h incubation of adipose tissue with [35S]methionine between PSL
      treated and untreated groups. These results indicate that degradation of LPL was
      inhibited in the adipose tissue of the PSL-treated group. In the adipose tissue
      of the untreated group, 72% of the LPL was the inactive-monomeric form, which was
      eluted with 0.4-0.75 M NaCl from the heparin-Sepharose column, and 28% was the
      active-dimeric form, which was eluted with 0.8-1.2 M NaCl. In the adipose tissue
      of the PSL-treated group, 40% was inactive-monomeric, and 60% was active-dimeric.
      Thus, the relative amount of the active-dimeric form of LPL was increased in the
      adipose tissue of the PSL-treated group. Taken together, our present results
      indicate that the higher level of LPL activity in the PSL-treated group was a
      result of the inhibition of the degradation of the active-dimeric form.

PMID- 12213491
TI  - Human colorectal cancer cells efficiently conjugate the cyclopentenone
      prostaglandin, prostaglandin J(2), to glutathione.
AB  - Cyclopentenone prostaglandins (PGs), particularly those of the J-series, affect
      proliferation and differentiation in a number of cell lines. J-ring PGs have been
      shown to be ligands for the peroxisome proliferator-activated receptor (PPAR)
      gamma and to modulate NF-kappaB-mediated gene transcription. We have previously
      reported that large quantities of eicosanoids, including PGJ(2), are produced by
      the human colorectal cancer cell line HCA-7 while lesser amounts of Delta(12)
      PGJ(2) and 15-deoxy-Delta(12,14)-PGJ(2) are formed. In this and other cell lines,
      cyclopentenone PGs have been shown to increase cell proliferation, but factors
      that influence their formation and metabolism are poorly understood. Unlike other
      PGs, cyclopentenone PGs contain alpha,beta-unsaturated carbonyl groups that
      readily adduct various biomolecules such as glutathione (GSH) in vitro. We now
      report that in HCA-7 cells, PGJ(2) is largely metabolized by conjugation to GSH.
      Characterization of the adducts by liquid chromatography (LC)-mass spectrometry
      (MS) revealed two major metabolites consisting of (1) a novel GSH conjugate in
      which the carbonyl at C-11 of PGJ(2) is reduced and (2) intact PGJ(2) conjugated
      to GSH. Approximately 70% of the PGJ(2) added to HCA-7 cells was esterifed to GSH
      after 2 h of incubation, suggesting this pathway represents the major route of
      metabolic disposition of PGJ(2) in HCA-7 cells.

PMID- 12213493
TI  - Oxylipin profiling in pathogen-infected potato leaves.
AB  - Plants respond to pathogen attack with a multicomponent defense response.
      Synthesis of oxylipins via the lipoxygenase (LOX) pathway appears to be an
      important factor for establishment of resistance in a number of pathosystems. In
      potato cells, pathogen-derived elicitors preferentially stimulate the 9-LOX
      dependent metabolism of polyunsaturated fatty acids (PUFAs). Here we show by
      oxylipin profiling that potato plants react to pathogen infection with increases
      in the amounts of the 9-LOX-derived 9,10,11- and 9,12,13-trihydroxy derivatives
      of linolenic acid (LnA), the divinyl ethers colnelenic acid (CnA) and colneleic
      acid (CA) as well as 9-hydroxy linolenic acid. Accumulation of these compounds is
      faster and more pronounced during the interaction of potato with the
      phytopathogenic bacterium Pseudomonas syringae pv. maculicola, which does not
      lead to disease, compared to the infection of potato with Phytophthora infestans,
      the causal agent of late blight disease. Jasmonic acid (JA), a 13-LOX-derived
      oxylipin, accumulates in potato leaves after infiltration with P. syringae pv.
      maculicola, but not after infection with P. infestans.

PMID- 12213492
TI  - Molecular characterization of the human PLC beta1 gene.
AB  - Inositide-specific phospholipase C (PLC) signaling constitutes a central
      intermediate in a number of cellular functions among which the control of cell
      growth raises a particular interest. Indeed, we have previously shown that
      nuclear phospholipase C beta1 (PLC beta1) is central for the regulation of
      mitogen-induced cell growth. We have also assigned by fluorescence in situ
      hybridization (FISH) analysis the PLC beta1 to human chromosome 20p12. In this
      study, we have carried out a detailed analysis of the human gene, showing the
      existence of alternative splicing, which gives rise, besides the two forms (1a
      and 1b) already shown in rodents, to a new 600 bp smaller form coding for a 110
      kDa protein. We have also identified a new exon at the 5', showing no homology
      with the rodent sequence. Here we provide the complete determination of the
      exon/intron structure of the gene spanning 250 kb of DNA. We found that the exons
      are quite small, ranging from 49 to 222 bp, while the introns vary between 108 bp
      and 34,400 bp. The availability of the understanding of the genome organization
      of this inositide-specific PLC, which represents a key step of the cell cycle
      related signaling, could actually pave the way for further genetic analysis of
      p12 region of human chromosome 20 in diseases involving alterations of the
      control of cell growth such as malignancies.

PMID- 12213494
TI  - Alterations of sarcolemmal phospholipase D and phosphatidate phosphohydrolase in
      congestive heart failure.
AB  - Phospholipase D 2 (PLD2) is the major PLD isozyme associated with the cardiac
      sarcolemmal (SL) membrane. Hydrolysis of SL phosphatidylcholine (PC) by PLD2
      produces phosphatidic acid (PA), which is then converted to 1,2 diacylglycerol
      (DAG) by the action of phosphatidate phosphohydrolase type 2 (PAP2). In view of
      the role of both PA and DAG in the regulation of Ca(2+) movements and the
      association of abnormal Ca(2+) homeostasis with congestive heart failure (CHF),
      we examined the status of both PLD2 and PAP2 in SL membranes in the infarcted
      heart upon occluding the left coronary artery in rats for 1, 2, 4, 8 and 16
      weeks. A time-dependent increase in both SL PLD2 and PAP2 activities was observed
      in the non-infarcted left ventricular tissue following myocardial infarction
      (MI); however, the increase in PAP2 activity was greater than that in PLD2
      activity. Furthermore, the contents of both PA and PC were reduced, whereas that
      of DAG was increased in the failing heart SL membrane. Treatment of the CHF
      animals with imidapril, an angiotensin-converting enzyme (ACE) inhibitor,
      attenuated the observed changes in heart function, SL PLD2 and PAP2 activities,
      as well as SL PA, PC and DAG contents. The results suggest that heart failure is
      associated with increased activities of both PLD2 and PAP2 in the SL membrane and
      the beneficial effect of imidapril on heart function may be due to its ability to
      prevent these changes in the phospholipid signaling molecules in the cardiac SL
      membrane.

PMID- 12213495
TI  - TRH decreases food intake and increases water intake and body temperature in
      rats.
AB  - Thyrotropin-releasing hormone (TRH) is a key regulator of the hypothalamus
      pituitary-thyroid axis, which plays an important role in energy homeostasis and
      is involved in the regulation of feeding behavior. In the present study, we
      investigated the effects of acute and chronic TRH treatment on water intake, body
      temperature and feeding behavior in rats. TRH (0, 4, 16 and 64 mg/kg) was
      injected subcutaneously twice a day (06:00 and 18:00 h) in rats fed ad libitum.
      TRH decreased food and water intake in the first few hours (P < .05). There was a
      small reduction in food intake over the 24-h period, but body weight was not
      affected (P < .05). When TRH was injected at a dose of 32 mg/kg twice a day
      (06:00 and 18:00 h) for 5 days, T(3) and T(4) concentrations were increased (P <
      .05). TRH increased body temperature for 2 h after injection. Water intake was
      markedly increased (P < .05), but there was no effect on food intake or body
      weight. These results show that whereas a single injection of TRH decreases short
      term food and water intake in rats, repeated daily treatments stimulate water
      intake but not food intake, and, thus, the increase in water consumption is
      mediated independently of food intake under these conditions.

PMID- 12213496
TI  - Uptake across the blood-brain barrier and tissue distribution of enterostatin
      after peripheral administration in rats.
AB  - Enterostatin, the N-terminal activation pentapeptide of procolipase that is
      produced by the pancreas, reduces food intake from high-fat diet when injected
      either peripherally or centrally to rats. We investigated uptake across the blood
      brain barrier (BBB) and tissue distribution of enterostatin by giving radioactive
      labeled enterostatin (3H-VPDPR) intravenously. Low levels of 3H-VPDPR were
      detected in many areas of the brain, with greatest radioactivity in the frontal
      cortex, hippocampus and cerebellum. Radioactivity was found in the plasma and all
      tissues, with the highest amount detected in the pancreas.

PMID- 12213497
TI  - Thermal control of mother-young contact revisited: hyperthermic rats nurse
      normally.
AB  - Morphine (MOR) is known to inhibit maternal behavior and induce hyperthermia; at
      appropriate doses, concurrent administration of naloxone (NAL) counteracts its
      disruption of maternal behavior but not the hyperthermia. We used these findings
      to evaluate the view that lactating rats terminate nursing due to intolerable
      hyperthermia. After a dam-litter separation of 4 h on Day 7 postpartum (PP),
      mother-litter interactions were observed continuously for 1 h. One hour before
      reunion, the dams received two injections (1 ml/kg ip each) of saline (SAL), MOR
      (20 mg/kg) and/or NAL (1 mg/kg) in the following combinations (n = 7 each): SAL +
      SAL, SAL + NAL, MOR + SAL or MOR + NAL. MOR profoundly disrupted maternal
      behavior, thereby preventing litter weight gains; these effects were completely
      counteracted by NAL, which alone had no discernible effects. In contrast, MOR
      induced hyperthermia (approximately 0.7 degrees C increase in each hour, before
      and after reunion with pups) was not antagonized by NAL at the doses used. Thus,
      an additional 0.7-1.4 degrees C of body temperature (T) did not delay the onset
      or reduce the duration of nursing compared with SAL-treated controls. Further,
      there were no group differences in behaviors displayed both shortly before and
      after a nursing bout that included milk ejections or in the resumption of
      nursing. Together with earlier methodological and empirical criticisms of the
      thermal control theory, as well as knowledge about the somatosensory determinants
      of nursing, the present results suggest that nursing bouts in lactating rats are
      not limited by the mother's T.

PMID- 12213498
TI  - Acute fasting decreases sexual receptivity and neural estrogen receptor-alpha in
      female rats.
AB  - Acute food deprivation or chronic food restriction suppresses reproduction in
      female mammals. Although a link between undernutrition and ovarian function is
      well established in rats, a similar link with reproductive behavior in this
      species is yet to be described. Therefore, we compared the display of estrous
      behaviors induced by exogenous steroid hormone treatment in ovariectomized fed
      and fasted rats. In addition, estrogen receptor-alpha immunoreactivity (ERIR) was
      measured in fed and fasted animals to determine whether changes in behavior were
      associated with changes in the number of detectable ERIR-containing cells in
      several brain regions. Fasting for 74 h decreased lordosis quotients (LQ) and
      lordosis ratings (LR) in ovariectomized, steroid-primed rats. The number of
      detectable ERIR cells decreased after a 74-h fast in the mid-region of the
      arcuate (ARC), paraventricular (PVN) and ventromedial nuclei of the hypothalamus
      (VMH) and the ventral bed nucleus of the stria terminalis (BST) but did not
      change in a number of other areas examined. Taken together, these data
      demonstrate that, similar to the effect on the reproductive-endocrine axis, food
      deprivation for 74 h suppresses steroid-induced display of lordosis in adult,
      female rats. Furthermore, this suppression in sexual receptivity is associated
      with a decrease in ERIR in a number of areas, including the VMH, a region of the
      hypothalamus known to be critical for the display of reproductive behaviors in
      female rats.

PMID- 12213499
TI  - Dominance, plasma testosterone levels, and testis size in house mice artificially
      selected for high activity levels.
AB  - Male house mice (Mus domesticus) from four replicate lines selectively bred for
      high voluntary wheel-running behavior were compared with four random-bred control
      lines with respect to dominance, testis size, and plasma testosterone level.
      Behavior was measured with a tube apparatus in which focal mice encountered a
      standard opponent from an inbred strain, and positions of mice were scored over a
      10-min period; the test was replicated the following day. Blood samples were
      taken from undisturbed mice 1 week prior to testing (baseline condition) and
      immediately after the first tube test; plasma testosterone was measured by enzyme
      immunoassay with chromatography. As compared with control lines, mice from
      selected lines tended to be smaller in body mass, to have larger testes, and were
      significantly less likely to advance towards their opponent during the second
      tube-test encounter. However, no significant differences in either baseline or
      post-encounter testosterone levels were detected. Significant differences in body
      mass, relative testis size, position during the first tube-test encounter, and
      baseline testosterone were found among the replicate lines within linetype, which
      indicates founder effects, random genetic drift, unique mutations, and/or
      multiple responses to selection. At the level of individual variation (residuals
      from nested analysis of covariance models), an inverse relationship between
      baseline testosterone and advancing in the tube test was observed, and the
      relationship was stronger during the second test day. This unexpected result may
      reflect an alternate coping strategy.

PMID- 12213500
TI  - Activity rhythm degrades after strenuous exercise in chronic fatigue syndrome.
AB  - Post-exertional exacerbation of symptoms is one of the major characteristics of
      chronic fatigue syndrome (CFS). In this study, we evaluated the hypothesis that
      disturbances in circadian chronobiological regulation may play a role in
      generating this phenomenon. We recorded physical activity for 6-day periods in 16
      women (10 CFS and 6 sedentary healthy controls, CON) before and after performing
      a maximal treadmill test. We calculated activity rhythms by computing
      autocorrelation coefficients by cutting 1 day apart from the data as a template
      and sliding it sequentially through each of the other days; all of 6 days were
      used as the templates. The peak value of autocorrelation coefficient (R) and the
      time between peak R's (circadian period, CP) were calculated. CFS patients had a
      lengthening (P < .05) of mean circadian period (MCP) that was longer than 24 h (P
      < .05), while MCP in CON remained unchanged. No difference was found in the
      standard error of each subject's MCP (circadian period variability, CPV) before
      and after exercise for both groups. We interpret this increase in circadian rest
      activity period seen in CFS patients following exercise to indicate that
      exhaustive exercise interferes with normal entrainment to 24-h zeitgeber(s). This
      effect may be associated in part with the common patient complaint of symptom
      worsening following exertion.

PMID- 12213501
TI  - A new animal model of binge eating: key synergistic role of past caloric
      restriction and stress.
AB  - Dieting and stress are important in the etiology and maintenance of eating
      disorders, and dieting strongly predicts stress-induced overeating in humans. We
      hypothesized that caloric restriction and stress interact in a unique manner to
      promote binge eating. To test this hypothesis, a group of young female rats were
      cycled through a restriction period (4 days of 66% of control food intake)
      followed by 6 days of free feeding prior to being stressed by acute foot shock.
      After three of these cycles, the food intake of rats exposed only to restriction
      (R), or only to stress (S), did not differ from controls. However, R+S rats that
      were restricted and refed, despite normal body weight and food intake after free
      feeding, engaged in a powerful bout of hyperphagia when stressed (Experiment 1).
      The R + S effect was replicated in an older group of rats (Experiment 2). The
      hyperphagia was characteristically binge-like, it constituted a 40% selective
      increase in highly palatable (HP) food (P < .001) over a discrete period of time
      (within 24 h post-stress), and reflected feeding for reward (higher HP:chow
      ratio) over metabolic need as occurred after restriction (higher chow:HP ratio).
      Subsequent experiments revealed that binge eating did not occur if only chow was
      available (Experiment 3) or if restriction-refeeding (R-R) did not proximally
      precede stress (Experiment 4). Experiment 5 revealed that a history of R-R cycles
      followed by only one stress episode was sufficient to increase intake to 53%
      above controls as early as 2 h after stress (P < .001). This animal model of
      binge eating should facilitate investigations into the neurochemical changes
      induced by dieting and environmental stress to produce disordered eating and
      provide a preclinical tool to test preventive strategies and treatments more
      relevant to bulimia nervosa, multiple cases of binge eating disorder (BED) and
      binge-purge type anorexia nervosa.

PMID- 12213502
TI  - Isolation rearing-induced deficits in prepulse inhibition and locomotor
      habituation are not potentiated by water deprivation.
AB  - Prepulse inhibition (PPI) of the acoustic startle reflex is an operational
      measure of sensorimotor gating and is reduced in neuropsychiatric disorders such
      as schizophrenia. Isolation rearing of rats is a developmentally specific,
      nonpharmacological manipulation that leads to deficits in sensorimotor gating
      that mimic those observed in schizophrenia patients. This study examined the
      effects of an added stressor (water deprivation) on the magnitude of the
      isolation rearing effect on PPI and locomotor activity. At the time of weaning,
      male (n = 80) and female (n = 80) rats were assigned to either social housing or
      isolation housing and were subsequently assigned to the water-deprived or non
      water-deprived groups. Rats were tested for acoustic startle and PPI at 3, 5 and
      7 weeks postweaning. Isolated rats showed a significant decrease in PPI that was
      apparent at all 3 weeks. Water deprivation did not significantly affect PPI, nor
      was there a significant interaction between housing and water treatment or
      between sex and housing. When tested in the Behavior Pattern Monitor to assess
      locomotor activity, isolated rats displayed decreased habituation across the 1-h
      test session. Water deprivation did not affect locomotor activity in any
      significant, independent manner, nor did it potentiate the effects of isolation
      rearing on locomotor habituation. In these studies, both male and female Long
      Evans rats were sensitive to the PPI-disruptive and locomotor-activating effects
      of social isolation. Isolation rearing significantly disrupts PPI and locomotor
      habituation independent of any effects of water deprivation.

PMID- 12213503
TI  - A study of VitalView for behavioural and physiological monitoring in laboratory
      rats.
AB  - We describe the use of a commercially available telemetry and data acquisition
      system to record heart rate, body temperature and activity of freely behaving
      rats with transmitters that operate without batteries (transponders). The system
      uses PDT 4000HR E-Mitters (Mini Mitter, OR, USA) to acquire animal temperature,
      heart rate and motor activity data. E-Mitters obtain power from a radiofrequency
      field produced by an ER-4000 energizer/receiver so that transponders can collect
      data on heart rate, body temperature and gross motor activity. ER-4000
      energizers/receivers are designed to be placed below the animals' cage. Data
      output from receivers is managed by a Windows PC-based data acquisition system,
      VitalView. In this study, we report that a good correlation exists between
      VitalView and Powerlab for the determination of heart rate and between intra
      abdominal (telemetric) and colonic body temperature (rectal digital thermometer)
      in rats. Assessment of this system by using agents that have well-documented
      effects on heart rate, body temperature and locomotor activity have also been
      determined. An additional feature of VitalView is the incorporation of
      behavioural inputs (feeding monitors to monitor duration and frequency of feeding
      and a lickometer to monitor drinking bouts) into the data acquisition system
      designed primarily to acquire data from the implanted transponders. Circadian
      rhythms for all parameters were established in rats with E-Mitters implanted.
      VitalView may be used for the determination of multiple parameters in freely
      behaving animals using transponders, which operate without batteries. This
      capability is unique in its field and represents a recent advance in
      biotelemetric monitoring of laboratory animals.

PMID- 12213504
TI  - Influence of chronic unpredictable stress on the allergic responses in rats.
AB  - The effects of chronic unpredictable stress on airway leukocyte infiltration and
      plasma extravasation in female rats have been investigated. The chronic stress
      lasted for 14 days and consisted of transitory and variable changes in the living
      conditions of the animals. Concomitant to the stress procedure, the animals were
      sensitized (Day 0) and challenged with ovalbumin (OVA; 200 microg) at Day 14.
      Bronchoalveolar lavage (BAL) was performed 48 h after intratracheal challenge
      with OVA (0.4 ml of a 0.25% solution). The increase in plasma extravasation was
      assessed by the rat paw oedema induced by OVA (0.1 mg/paw) or the mast cell
      degranulator compound 48/80 (5 microg/paw). A significant increase (P < .05) in
      the total leukocyte influxes into the airways was observed in the stressed
      (sensitized) group compared to nonstressed (sensitized) animals, and this was
      associated with a marked recruitment of eosinophils and mononuclear cells in the
      BAL fluid. In OVA-sensitized rats, intraplantar injection of OVA induced a marked
      paw oedema that was significantly higher in stressed compared to nonstressed
      groups. In contrast to OVA, the compound 48/80 (5 microg/paw)-induced oedema did
      not significantly differ between nonstressed and stressed groups. Our results
      indicate that chronic unpredictable stress exacerbates the vascular and cellular
      inflammatory responses.

PMID- 12213505
TI  - Dietary fat content affects energy intake and weight gain independent of diet
      caloric density in rats.
AB  - Recent considerations of high-fat diet hyperphagia have focused on fat's
      relatively high energy density as the critical variable which promotes
      overeating. However, a high-fat (HF) diet has been shown to enhance intake and
      weight gain relative to a high-carbohydrate (HC) diet when both energy density
      and palatability are equated [Am. J. Physiol. 269 (1995) R30]. The present
      studies investigated the generality of this finding across manipulations of diet
      caloric density, diet physical form, and chow availability. Separate groups of
      male rats were fed HF or HC at either 2.3 or 1.15 kcal/ml for 16 days; HF feeding
      enhanced weight gain relative to HC across both levels of energy density. HF
      hyperphagia also occurred when diets were presented in semisolid (gelled) form,
      and when chow was available in addition to liquid diet. These findings are
      consistent with previous observations that an HF diet can enhance daily
      kilocalorie intake and weight gain at least partly via a mechanism that is
      unrelated to caloric density.

PMID- 12213506
TI  - The development of infants' circadian rest-activity rhythm and mothers' rhythm.
AB  - In order to know when and how infants obtain their circadian sleep-wake rhythm,
      infants' developing circadian rest-activity rhythm and mothers' circadian rhythm
      in the postpartum period were examined using actigraph monitoring. The subjects
      were 11 primipara and their infants. Actigraphic recordings for the infants and
      their mothers were made over 3-5 continuous days during the 3rd, 6th, 9th and
      12th weeks after birth. A 24-h peak on a mean autocorrelogram of the infants'
      movements was detected at the 3rd week. The infants' circadian rest-activity
      rhythm already existed in the 3rd week. The amplitude of this 24-h peak gradually
      increased from the 6th to 12th week. This may be useful as an index of the
      development of infants' circadian rest-activity rhythm. An 11-h peak was also
      observed at the 3rd week. This 11-h peak was thought to be a semi-circadian
      rhythm. Regarding the mothers, the amplitude of the 24-h peak on the mean
      autocorrelogram at the 3rd week was the smallest of all other weeks, and it
      became larger from the 3rd to 12th week. This meant that the mothers' circadian
      rhythm at the 3rd week was influenced by their interrupted sleep at night to take
      care of their infants. The mother-infant synchronization is probably the 1st
      factor in the entrainment of infants' circadian sleep-wake rhythm. In this study,
      we also propose a novel method for compensating for missing data in
      autocorrelogram analysis.

PMID- 12213507
TI  - The effect of bulimia nervosa on plasma glucose and lipids.
AB  - This analysis examined changes in plasma lipids and glucose after 3 years in
      women treated for bulimia nervosa (BN). One hundred and thirty-five women aged 17
      45 years with DSM-III-R BN entered a 12-week cognitive behavioral therapy
      treatment programme. Prior to and 3 years after treatment, patients completed
      psychiatric and behavioral assessments and fasting blood samples were drawn. At 3
      year follow-up, 105 women were available, 67.6% of whom had no eating disorder
      and 32.4% of whom had any eating disorder (16.2% with eating disorder not
      otherwise specified and 16.2% with BN). Women with no eating disorder diagnosis
      at 3-year follow-up experienced a significant mean decrease in plasma glucose
      from pretreatment to 3-year follow-up compared to those with any eating disorder
      diagnosis. Eating disorder diagnosis at 3-year follow-up was independently
      associated with change in plasma glucose when potential confounders were adjusted
      for. Plasma triglyceride concentrations did not change in the group as a whole.
      Plasma HDL-cholesterol increased and total cholesterol decreased significantly
      from pretreatment to 3-year follow-up in the group as a whole. The decrease in
      serum cholesterol was significant in women with no eating disorder, but not in
      the women with any eating disorder diagnosis at 3-year follow-up. We conclude
      that a protracted course of BN may result in clinically insignificant increases
      in glucose concentrations and may attenuate the decrease in total cholesterol
      that is observed in women who recover from BN.

PMID- 12213508
TI  - Nicotine-induced conditioned place preference in adolescent and adult rats.
AB  - About 1 million American adolescents start smoking every year. Adolescents may be
      unusually sensitive to certain consequences of nicotine, demonstrating, for
      instance, significantly higher rates of dependence than adults at the same level
      of nicotine use. To explore whether adolescents may be more sensitive to
      rewarding properties of nicotine than adults, the present study used an animal
      model to assess the rewarding effects of a low nicotine dose (0.6 mg/kg) in a
      conditioned place preference (CPP) paradigm. Locomotor activity during
      conditioning and testing was also evaluated. Nicotine was observed to induce
      place preference conditioning in adolescent Sprague-Dawley rats, whereas the
      training dose of 0.6 mg/kg failed to produce convincing place preference in their
      adult counterparts. Age differences were also apparent in terms of nicotine
      influences on motor activity, with adults being more sensitive to nicotine
      suppressant effects and only adolescents showing an emergence of nicotine
      stimulatory effects upon repeated exposures. An increased predisposition to
      stimulatory nicotine effects during adolescence may contribute to age-specific
      rewarding properties of the drug as revealed using the CPP paradigm in this
      experiment. Increased sensitivity to stimulatory and rewarding effects during
      adolescence could potentially contribute to the high rate of nicotine use and
      dependence among human adolescents.

PMID- 12213509
TI  - Effects of the selective dopamine D(1) antagonists NNC 01-0112 and SCH 39166 on
      latent inhibition in the rat.
AB  - Dopamine D(1) receptor blockade does not appear to be a prerequisite for
      antipsychotic activity since many clinically effective antipsychotics have little
      or no affinity for this receptor subtype. Clozapine, however, which has minimal
      liability for extrapyramidal symptoms, possesses affinities of similar order for
      D(1) and D(2) receptors. In earlier animal models used to predict antipsychotic
      effect, selective D(1) antagonists have shown effects similar to standard
      antipsychotics with preferential D(2) or mixed D(1)/D(2) antagonism. We
      investigated the effects of haloperidol (0.1 mg/kg) and two selective D(1)
      antagonists, NNC 01-0112 (0.05, 0.1 and 0.2 mg/kg) and SCH 39166 (0.02, 0.2 and
      2.0 mg/kg), on latent inhibition (LI) in rats. LI is a behavioural paradigm in
      which repeated nonreinforced preexposure to a stimulus retards subsequent
      associations to that stimulus. Disrupted LI has been suggested as a model for the
      attentional deficits in schizophrenia. Using preexposure to a flashing light
      stimulus, which subsequently served as a conditioned stimulus for suppression of
      water licking, we demonstrated a clear LI effect with haloperidol but with
      neither of the two D(1) antagonists. Since selective D(1) antagonists are not
      clinically effective, these results add further credibility for the relevance of
      LI as an animal model of psychosis.

PMID- 12213510
TI  - Effects of chronic dysthyroidism on activity and exploration.
AB  - The aim of the present study was to determine the influence of thyroid function
      on the activity and exploratory behaviour of male Wistar rats. Dysthyroidism was
      induced by adding drugs to their drinking water from the ninth day of gestation.
      This method is not as stressful as daily thyroxine injections or thyroidectomy,
      and therefore did not affect the analysed behavioural patterns. After weaning,
      the drugs were administered to the young rats until the end of the experiment.
      Activity and exploration were measured using the Boissier test, a light-darkness
      test and an open-field test when they were 77 days old. In order to verify that
      the animals' motor capacity had not been impaired, a psychomotor battery was
      used. Chronic hyperthyroidism produced a significant increase in activity, but
      did not affect exploration. On the other hand, hypothyroidism did not affect
      activity, but did increase exploration. This increase in exploration was observed
      in activity-independent behavioural parameters, such as head dipping and
      glancing.

PMID- 12213511
TI  - Area postrema lesions elevate NPY levels and decrease anxiety-related behavior in
      rats.
AB  - Intracerebroventricular administration of neuropeptide Y (NPY) has been shown to
      reduce anxiety-like effects in rodents and also profoundly alter feeding. The
      area postrema-lesioned (APX) rat model of food motivated behavior overconsumes
      palatable foods and expresses significantly higher levels of NPY in the
      hypothalamus than sham-lesioned control rats. For this reason, we examined APX
      rats in the open field test, which is a standard measure of anxiety- or fear
      related behavior and also investigated NPY mRNA levels in the hippocampus,
      amygdala and hypothalamus. We found that APX rats display reduced anxiety-like
      behavior in the open field test as indicated by spending increased time in the
      center of the field as opposed to the perimeter of the field. NPY mRNA levels
      were also found to be significantly elevated in the amygdala, hippocampus and
      arcuate nucleus of the hypothalamus of APX rats when compared to sham-lesioned
      rats. These results support the action of limbic NPY to reduce anxiety-like
      behavior in a rodent model that appears to express higher than normal NPY levels.

PMID- 12213512
TI  - Dietary composition alters gentamicin-induced nephrotoxicity in rats.
AB  - Previous studies have shown temporal variations in gentamicin-induced renal
      toxicity characterized by a peak when administered during the resting period and
      a trough during the active period. This time-dependent toxicity was also altered
      according to the macronutrient composition of dietary regimens offered to female
      rats. In the present study, adult female Sprague-Dawley rats were adapted to
      semipurified isocaloric diets containing 20% casein or soy-protein (10% fat each)
      or to a standard chow diet (18.1% mixed proteins; 4.5% fat). The animals were
      then chronically treated for 10 days with a nephrotoxic dose of gentamicin
      sulfate (40 mg/kg/day ip) or a saline solution administered in the middle of
      their resting period (1200 h) or in the middle of their activity period (0000 h).
      Body weights of rats injected in the middle of their resting period decreased
      over the last 6 days of gentamicin treatment. Total 12-h light and 12-h dark food
      intakes were decreased in gentamicin-treated rats. Rats fed the standard chow
      diet had significantly lower corticocellular regeneration, serum creatinine and
      blood urea nitrogen compared to those fed the casein- and soy-containing diets.
      The present study demonstrates that chronic gentamicin-induced renal toxicity
      varies temporally according to the time of administration and that a mixed
      protein diet containing a lower fat level can protect against gentamicin-induced
      nephrotoxicity.

PMID- 12213513
TI  - Induction of maternal behavior in non-parturient adoptive mares.
AB  - An attempt was made to elicit maternal behavior in non-parturient Welsh pony
      mares through a combination of hormonal treatment and vaginal-cervical
      stimulation (VCS). Lactation was induced in 16 nonpregnant, non-parturient mares
      via a combination of estradiol, progesterone and a dopamine antagonist
      (sulpiride). During the adoption trials, each lactating mare was confined behind
      a padded bar and a newborn foal was held near her head. Eight of the mares
      received two 3-min periods of VCS when the foster foal was introduced. Following
      VCS, the foal was released and its interactions with the adoptive mare observed
      until the acceptance criterion was met (i.e. the mare accepted the foal at the
      udder with no signs of aggression). The remaining eight adoptive mares were
      treated in the same manner but did not receive VCS. All 16 non-parturient mares
      eventually accepted and nursed their adopted foal. However, acceptance latencies
      were significantly shorter for mares in the VCS condition than for those without
      VCS, and did not differ between the VCS condition and a group of control mares
      with their biological offspring. In subsequent choice tests, both groups of
      foster mares (with/without VCS), like the control mares, displayed a preference
      for their 'own' foal. Once the non-parturient mares accepted their foster foal,
      their maternal behavior resembled that of control mothers. The positive effect of
      VCS on maternal acceptance may reflect a release of oxytocin triggered by this
      treatment.

PMID- 12213514
TI  - Alpha-adrenergic control of ANG II-induced drinking in the rat median preoptic
      nucleus.
AB  - The present study was carried out to investigate the contribution of
      angiotensinergic and catecholaminergic systems in the median preoptic nucleus
      (MnPO) to the drinking response elicited by activation of the subfornical organ
      (SFO) following injections of angiotensin II (ANG II) in the awake unrestrained
      rat. Microinjection of ANG II into the SFO caused the drinking response. The
      water intake caused by ANG II injected into the SFO was significantly enhanced by
      previous injections of phenylephrine, an alpha-adrenoceptor agonist, but not by
      isoprenaline, a beta-adrenoceptor agonist. Previous injections of either
      saralasin, a specific ANG II antagonist, or phentolamine, an alpha-adrenoceptor
      antagonist, into the MnPO significantly attenuated the water intake caused by the
      ANG II injection into the SFO. Similar injections of timolol, a beta-adrenoceptor
      antagonist, or the vehicle into the MnPO had no significant effect on the
      drinking response. These results show the involvement of both angiotensinergic
      and alpha-adrenergic systems in the MnPO in the drinking response induced by ANG
      II acting at the SFO, and imply that the alpha-adrenergic system may serve to
      enhance the neural inputs including the angiotensinergic inputs from the SFO,
      thereby causing increased dipsogenic response.

PMID- 12213515
TI  - Gnawing behavior of a mouse in a narrow cylinder: a simple system for the study
      of muscle activity, fatigue, and stress.
AB  - When a mouse is put into a cylinder too narrow for it to turn (its front end
      being blocked with a thin plastic strip), the mouse gnaws away the plastic to
      escape. Hence, the weight reduction in the plastic can be used as an index of
      'gnawing activity (GA).' GA was high at first, but decreased with time. Training
      augmented GA, but not the activity of the histamine-forming enzyme (histidine
      decarboxylase [HDC]: a proposed marker of muscle fatigue) in the masseter muscle.
      In trained mice, GA was higher at night than in the daytime, and was decreased by
      starvation. In mice prevented from reaching the strip, the elevation of serum
      cortisol was greater than that seen in mice able to gnaw at it. As such gnawing
      is a form of voluntary behavior, these results suggest that our experimental
      system may be useful for (i) the quantitative study of voluntary muscle activity
      associated with physical or mental fatigue or motivation, and (ii) the study of
      an animal's response to stress when it has, or alternatively does not have, an
      apparent way of escape.

PMID- 12213516
TI  - Attractive properties of sexual pheromones in mice: innate or learned?
AB  - It is generally assumed that chemical signals (sexual pheromones) constitute the
      primary stimulus for sexual attraction in many mammals. However, it is unclear
      whether these pheromones are volatile or nonvolatile and which sensory systems
      are involved in their detection (vomeronasal and/or olfactory). Moreover, it has
      been demonstrated that experience influences the behavioral response to sexual
      pheromones and the sensory systems implicated. In order to clarify this issue,
      the attractive properties of volatile and nonvolatile components of the male
      soiled bedding have been analyzed in female mice that had no previous experience
      with adult male-derived chemical signals (chemically naive females) using two
      choice preference tests. The results indicate that some nonvolatile male-derived
      substances exert an innate attraction to females, but volatiles derived from male
      soiled bedding do not attract chemically nai;ve females. Therefore, the primary
      attractive sexual pheromone includes a nonvolatile compound (e.g. major urinary
      proteins, MUPs). On the other hand, male-derived volatiles become attractive to
      females because of repeated exposure to male-soiled bedding. This represents a
      Pavlovian-like associative learning in which previously neutral volatiles (very
      likely odorants) acquire attractive properties by association with the
      nonvolatile, innately attractive pheromone(s). These findings indicate that not
      only the sexual but also the 'chemical' experience (previous experience with
      sexual pheromones) has to be taken into account to interpret the role of
      chemicals as releaser or primer pheromones. The sensory systems involved in the
      detection of these stimuli and the neural basis of the odor-pheromone association
      are discussed.

PMID- 12213517
TI  - Differential subjective effects of D-amphetamine by gender, hormone levels and
      menstrual cycle phase.
AB  - Estrogen and progesterone interact with monoamines in ways that suggest the
      potential modulation of responses to psychoactive drugs by endogenous steroids,
      both between menstrual phases and between the sexes. The present study assessed
      the subjective and physiological effects of a single dose of D-amphetamine (AMPH;
      15 mg oral) in healthy, normally cycling women (n=13), who received amphetamine
      and placebo (PL) during both the follicular and luteal phases of a single
      menstrual cycle, and in healthy men (n=7). Females reported greater amphetamine
      induced subjective stimulation [Addiction Research Center Inventory (ARCI)-A,
      ARCI-MBG; Drug Effects Questionnaire (DEQ) Feel Drug, Feel High, Want More]
      during the follicular phase than the luteal phase. Within the follicular phase,
      the magnitude of individuals' AMPH-induced stimulation was positively associated
      with baseline (predrug) salivary estradiol [r=+.55-.78; Profile of Mood States
      (POMS) Vigor, Positive Mood, Elation], and negatively associated with salivary
      progesterone [r=-.66-.68; POMS Friendliness; Subjective States Questionnaire
      (SSQ) Pleasant Sedation]. Sex differences also emerged. Males reported feeling
      greater AMPH-induced stimulation (ARCI-A, ARCI-MBG; DEQ Feel Drug, Want More)
      than females in the luteal phase. Thus, higher levels of estrogen and lower
      levels of progesterone are associated with greater subjective stimulation after
      AMPH in women, and these hormonal influences contribute to sex differences in
      amphetamine responding.

PMID- 12213518
TI  - Vaginal lavage attenuates cocaine-stimulated activity and establishes place
      preference in rats.
AB  - Sex and estrous cycle stage affect psychostimulant responses in animals. Cycle
      stage is typically monitored by vaginal lavage. The present studies tested the
      hypothesis that vaginal lavage modifies behavioral responses to acute cocaine.
      Female rats were restrained by briefly holding the tail for either vaginal lavage
      or touching the thigh, or were undisturbed, for 7-10 days prior to testing.
      Although habituation to the open-field test chamber was equal in each group,
      repeated lavage decreased horizontal activity relative to naive rats following
      acute cocaine (10 mg/kg ip). Lavage and touch attenuated cocaine-stimulated
      vertical activity. A single lavage prior to testing did not affect cocaine
      stimulated motor behavior. Estrous cycle influenced motor activity only in
      nonlavaged rats. The high cocaine-induced responding observed in proestrous and
      estrous nonlavaged rats was completely blocked by vaginal lavage. A separate
      experiment tested the ability of vaginal lavage to establish a conditioned place
      preference. Vaginal lavage immediately prior to the conditioning session, but
      neither lavage after conditioning nor touch before, induced a significant
      preference. These results suggest that vaginal lavage serves as a reinforcing
      stimulus and interacts with a neural substrate that mediates enhanced locomotor
      responses to cocaine during proestrus and estrus.

PMID- 12213519
TI  - Reevaluation of PNU-99194A discriminative stimulus effects: potentiation by both
      a D2 antagonist and a D3/D2 agonist.
AB  - This study evaluated the relative importance of D(3) receptor antagonism in the
      discriminative stimulus effects of the putative D(3) receptor antagonist PNU
      99194A. Eight male Sprague-Dawley rats were trained to discriminate PNU-99194A
      (10 mg/kg sc) from vehicle in a two-choice drug discrimination procedure under a
      FR 20 schedule of food reinforcement. The selective D(3) antagonists PD 152255
      and S14297 were examined for stimulus generalization. The D(2) antagonist
      haloperidol and the D(2)/D(3) receptor agonist (+)-7-OH-DPAT were also assessed
      for antagonism of PNU-99194A discrimination. PD 152255 (1.0-3.0 mg/kg) engendered
      no generalization to PNU-99194A. Due to its markedly rate-suppressive effects, PD
      152255 could not be tested at higher doses. S-14297 produced partial substitution
      (66%) for PNU-99194A at both 3.0 and 8.0 mg/kg. Neither haloperidol nor (+)-7-OH
      DPAT blocked the discrimination of PNU-99194A and, surprisingly, actually
      appeared to potentiate its effects. These data, along with other recent findings,
      suggest that the discriminative stimulus effects of PNU-99194A appear to involve
      complex pharmacological actions and are not solely mediated by D(3) receptor
      antagonism.

PMID- 12213520
TI  - Prenatal protein malnutrition enhances stimulus control by CDP, but not a
      CDP/THIP combination in rats.
AB  - In the present study, the effects of prenatal protein malnutrition on stimulus
      control exerted by the benzodiazepine (BZ), chlordiazepoxide (CDP) and the GABA-A
      receptor agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) were
      characterized. The adult, male offspring of female Sprague-Dawley rats fed either
      low (6% casein) or adequate (25% casein) protein diets 5 weeks prior to mating
      and throughout pregnancy served as subjects. Subjects were first trained to
      discriminate CDP (8.0 mg/kg ip) from saline using drug discrimination procedures.
      Once a criterion level of performance was achieved, generalization tests were
      performed to lower doses of CDP (4.0, 2.0, 1.0, 0.5 and 0.25 mg/kg) and then to
      several doses of THIP (10.0, 7.5, 5.6 and 3.2 mg/kg). Lastly, the ability of a
      single dose of THIP (3.0 mg/kg) to enhance discriminative control by several low
      doses of CDP (4.0, 2.0, 1.0 and 0.5 mg/kg) was assessed. Although both diet
      groups acquired the original CDP/saline discrimination at the same rate,
      malnourished rats exhibited significantly more generalization to low doses of CDP
      than their well-nourished counterparts. Neither diet group exhibited significant
      generalization to THIP nor a difference in THIP's ability to enhance the CDP cue.
      These results suggest that a subject's sensitivity to the stimulus properties of
      drugs can be selectively modified by prenatal malnutrition.

PMID- 12213521
TI  - Effects of cocaine and putative atypical antipsychotics on rat social behavior:
      an ethopharmacological study.
AB  - The effects of cocaine, amperozide, clozapine, olanzapine and cocaine/atypical
      antipsychotic combinations on aggression, affiliation and defensive behaviors was
      examined. Acute cocaine (30.0 mg/kg) decreased basal aggression and affiliation
      yet increased basal defense. Amperozide (1.0, 3.0 and 5.0 mg/kg) decreased basal
      aggression, affiliation and defense had no effect on the cocaine-induced decrease
      in affiliation, and accentuated the cocaine-induced decrease in aggression. Near
      basal levels of defense were observed for animals treated with either amperozide,
      clozapine (3.0 and 10.0 mg/kg but not 30.0 mg/kg) or olanzapine followed by
      cocaine. Clozapine (3.0, 10.0 and 30.0 mg/kg) decreased basal aggression and
      affiliation. Clozapine (30.0 mg/kg but not 3.0 or 10.0 mg/kg) decreased basal
      defense. Clozapine attenuated the cocaine-induced decrease in aggression.
      Although 3.0 and 10.0 mg/kg clozapine attenuated the cocaine-induced decrease in
      affiliation, 30.0 mg/kg clozapine accentuated this cocaine-induced effect.
      Olanzapine (1.0, 3.0 and 10.0 mg/kg) decreased basal aggression, affiliation and
      defense. Olanzapine had no effect on the cocaine-induced decrease in aggression.
      Olanzapine (3.0 mg/kg but not 1.0 or 10.0 mg/kg) attenuated the cocaine-induced
      decrease in affiliation. Thus, acute cocaine administration had an antiaggressive
      effect, suppressed affiliative behavior and enhanced defensive behavior.
      Amperozide, clozapine and olanzapine have anticonflict and anxiolytic effects, as
      well as potent and specific antiaggressive effects.

PMID- 12213522
TI  - Sigma sites mediate DTG-evoked hypothermia in rats.
AB  - 1,3,-Di-o-tolylguanidine (DTG), a sigma agonist, produces hypothermia in rats,
      but the inability of purported sigma antagonists to block the hypothermia
      suggests that sites other than sigma may mediate the effect. Recently, N-[2-(3,4
      dichlorophenyl) ethyl]-N-methyl-2-(dimethylamino) ethylamine (BD 1047) has been
      identified as a functional sigma antagonist in vivo because of its high
      selectivity for sigma sites and its ability to block DTG-induced dystonia and
      cocaine-evoked behaviors. Therefore, the present study investigated the effect of
      BD 1047 on DTG-evoked hypothermia. DTG (1, 10, 20 and 30 mg/kg sc) induced dose
      dependent hypothermia. The onset of DTG-induced hypothermia was rapid, with a
      reduction in body temperature observed 15 min postinjection. To determine whether
      sigma sites mediated DTG-induced hypothermia, BD 1047 was injected 30 min prior
      to DTG. BD 1047 (1, 5, 7.5 and 10 mg/kg sc) attenuated the hypothermia in a dose
      dependent fashion, thus revealing a sigma site mechanism. The injection of BD
      1047 alone did not alter body temperature, suggesting that endogenous sigma
      systems do not play a tonic role in thermoregulation. The present experiments
      demonstrate for the first time that a selective sigma antagonist attenuates sigma
      agonist-induced hypothermia. Moreover, these data provide further evidence that
      BD 1047 is an effective antagonist for characterizing sigma-mediated effects in
      vivo.

PMID- 12213523
TI  - Asymmetric serial interactions between ethanol and cocaine in taste aversion
      learning.
AB  - Although the interaction between ethanol and cocaine is well documented, it has
      generally been limited to situations in which the two drugs are given
      concurrently. Little exists on the interaction between ethanol and cocaine when
      one drug is given prior to the other. In Experiment 1, female Long-Evans rats
      were given five exposures to ethanol (2 g/kg ip) or vehicle prior to taste
      aversion conditioning with cocaine (32 mg/kg sc) for a total of five conditioning
      trials. In Experiment 2, rats were given five exposures to cocaine (32 mg/kg sc)
      or vehicle prior to taste aversion conditioning with ethanol (2 g/kg ip) for a
      total of five conditioning trials. Ethanol-preexposed, cocaine-conditioned
      animals (Experiment 1) displayed attenuated aversions to the cocaine-associated
      solution, drinking significantly greater amounts of saccharin than vehicle
      preexposed, conditioned subjects. Conversely, cocaine-preexposed, ethanol
      conditioned animals (Experiment 2) displayed robust aversions to the ethanol
      associated solution, drinking levels comparable to those consumed by vehicle
      preexposed, conditioned subjects and drinking significantly less than controls.
      Although the basis for these asymmetric effects is not known, they may have
      implications for abuse vulnerability in that drug history may impact subsequent
      drug toxicity that, in turn, may alter drug acceptability.

PMID- 12213524
TI  - Effects of N-acetylcysteine on macrophage and lymphocyte functions in a mouse
      model of premature ageing.
AB  - In previous studies, we have observed that mice of the same strain and age show
      striking interindividual differences in behavior when exposed to a T-maze test.
      The animals that take longer to explore a T-shaped maze ("slow" animals) show
      high levels of emotionality/anxiety in other standard behavioral tests,
      prematurely aged immune functions, and a shorter life span, in comparison to
      "fast" mice. In these slow mice, which are a model of premature immunosenescence,
      the immune functions were improved after the ingestion of the thiolic antioxidant
      thioproline in the diet. In the present work, we studied the effects in vivo
      (0.1% w/w, for 4 weeks) and in vitro (0.001, 0.01, 0.1, 1, and 2.5 mM) of the
      thiolic antioxidant N-acetylcysteine (NAC) on different functions of peritoneal
      macrophages and lymphocytes from slow and fast adult Swiss mice. The results
      showed an improvement of all the functions studied, namely adherence to
      substrate, directed migration or chemotaxis, phagocytosis, and reactive oxygen
      species (ROS) production, after in vivo and in vitro treatment with NAC. The
      effect of this antioxidant was stronger in the cells from the slow than in those
      from the fast mice.

PMID- 12213525
TI  - Effects of melatonin injection on running-wheel activity and body temperature
      differ by the time of day.
AB  - Melatonin, which is released from the pineal gland, influences many physiological
      events concerned with circadian rhythm. Body temperature levels and rhythmicity
      are tightly coupled with locomotor activity. To understand the functions of
      melatonin, we determined the effects of melatonin injection on locomotor activity
      measured by running-wheel activity and body temperature in rats. The rats were
      kept under a 12-h light and 12-h dark lighting condition, with the light on at
      zeitgeber time 0 (ZT 0, correspond to 7:00 JST). Melatonin injection, between ZT
      3 and ZT 5 (light period) and between ZT 15 and ZT 17 (dark period), attenuated
      the wheel-running activity in a dose-dependent manner (10 microg to 1 mg/100 g
      body weight [bw]). A significant attenuation of activity by melatonin was
      recognized when injected at ZT 8, ZT 14 and ZT 20. After the injection of
      melatonin, the animal's body temperature was elevated at ZT 2 and ZT 8 (during
      light), while it fell at ZT 14 and ZT 20 (during darkness). We propose a
      plausible explanation underlying the observed changes in body temperature during
      the light and dark periods accompanying the suppression of activity induced by
      melatonin.

PMID- 12213526
TI  - Iron deficiency in rats decreases acquisition of and suppresses responding for
      cocaine.
AB  - Iron deficiency impairs nigrostriatal and mesolimbic dopamine systems by causing
      decreased densities of D(1) and D(2) receptors and the dopamine transporter in
      the terminal fields, caudate-putamen and nucleus accumbens. Iron deficiency also
      causes deficits in dopamine-related pharmacological indices, e.g., deficits in
      locomotor stimulation by cocaine and locomotor inhibition by raclopride. Based on
      this knowledge, we hypothesized that iron deficiency would have a major impact on
      cocaine self-administration. Male Sprague-Dawley rats were fed an iron-deficient
      diet starting at weaning (Day 21) and continuing throughout the experiment. At 57
      58 days of age, all animals had catheters implanted surgically into the jugular
      vein. Approximately 2 weeks later, all animals were trained to lick an empty
      spout for intravenous cocaine, delivered by infusion pump at 0.33 mg/kg. During
      the course of training, all animals acquired intravenous cocaine self
      administration, however, the course of acquisition was significantly slower for
      the iron-deficient animals. When tested for responding on a progressive ratio
      (PR) schedule, the control animals maintained a constant number of infusions,
      whereas the responding of the iron-deficient animals fell off sharply. When the
      dose of cocaine was decreased, control, but not iron-deficient adjusted the
      amount administered by increasing the number of infusions. Finally, the failure
      to respond by the iron-deficient animals was not simply due to a failure to lick
      (i.e., a motor impairment), because both the iron-deficient and the control
      animals emitted approximately 1000 licks/20 min session when given free access to
      a palatable 0.1 M sucrose solution. Taken together, the data show that severe
      iron deficiency early in life can diminish the capacity of cocaine, but not
      sucrose to reinforce behavior. The question raised by this research thus, is
      whether iron deficiency alters hedonic-like responses only to dopamine-related
      behaviors and the degree to which willingness to "work" contributes to the
      effect.

PMID- 12213527
TI  - Genetic variation in morphine analgesic tolerance: a survey of 11 inbred mouse
      strains.
AB  - The present study assessed the analgesic potency of morphine in 11 inbred mouse
      strains before and after chronic morphine treatment. Using the 49 degrees C tail
      withdrawal test, significant strain differences in morphine AD(50) estimates
      derived from cumulative dose-response curves were noted prior to tolerance
      induction on Day 1. AD(50) estimates were reassessed on Day 4, after three daily
      systemic morphine injections for 3 days using an escalating dose schedule (10,
      20, and 40 mg/kg sc). In 9 of 11 strains, morphine potency was significantly
      reduced from 2-fold to as much as 11-fold. Two strains (129P3 and LP) displayed
      no evidence whatsoever of tolerance development. Neither initial baseline
      withdrawal latency nor morphine analgesic sensitivity was significantly
      correlated with tolerance magnitude. Also observed were strain-dependent
      alterations (mostly hyperalgesia) in baseline tail-withdrawal latencies as a
      result of chronic morphine treatment. The magnitude of hyperalgesia and analgesic
      tolerance was significantly correlated among strains, implicating common genetic
      substrates and supporting their proposed association. The present work
      demonstrates that the presence and magnitude of morphine analgesic tolerance is
      genotype-dependent and identifies strains with widely divergent liabilities that
      should facilitate identification of trait-relevant genes.

PMID- 12213528
TI  - Effects of anticholinergics on serial-probe recognition accuracy of rhesus
      macaques (Macaca mulatta).
AB  - Potential deleterious behavioral effects of the anticholinergics biperiden and
      scopolamine were examined via the performance of rhesus monkeys on a serial-probe
      recognition (SPR) procedure. On each trial, six unique stimuli (list items) were
      presented sequentially followed by a choice phase. In the choice phase, two
      stimuli were presented, a standard or 'default' stimulus (a white rectangle) and
      a 'probe' stimulus that differed with each choice trial. Choosing the probe
      stimulus was considered correct if the probe matched one of the list items;
      otherwise, choosing the default stimulus was considered correct. Behavior was
      examined under a range of doses of biperiden (0.001-1.0 mg/kg) and scopolamine
      (0.0056-0.03 mg/kg). Scopolamine (0.01-0.03 mg/kg) and biperiden (0.3-1.0 mg/kg)
      reduced overall accuracy. At the highest dose, scopolamine, but not biperiden,
      reduced the number of trials completed per session. The results suggest that
      doses of scopolamine and biperiden necessary to prevent or eliminate
      organophosphate induced seizures may affect performance adversely. However,
      because the degree of impairment from biperiden was modest, further examination
      of this anticonvulsant may be warranted.

PMID- 12213529
TI  - Behavioral sensitization to amphetamine follows chronic administration of the CB1
      agonist WIN 55,212-2 in Lewis rats.
AB  - The extent to which acute and repeated administration of the CB(1) agonist WIN
      55,212-2 would affect the stimulatory properties of amphetamine was assessed in
      Lewis rats. In the first experiment, Lewis rats were treated with either 1 mg/kg
      of WIN 55,212-2 or vehicle and subsequently treated with 2 mg/kg amphetamine.
      Acute treatment with WIN 55,212-2 initially increased locomotor activity and then
      attenuated the stimulating effect of amphetamine on locomotion and exploration
      (as measured by rears). In a separate experiment, Lewis rats were given daily
      injections of either WIN 55,212-2 (1 mg/kg) or vehicle for 10 days and the
      effects of amphetamine were assessed at 1 and 3 days following the last chronic
      cannabinoid treatment. Those rats, which had been treated with WIN 55,212-2, had
      an enhanced response to amphetamine with rearing but not with ambulatory
      movements, suggesting the occurrence of behavioral cross-sensitization to the
      ability of amphetamine to increase rearing. These data add to the growing
      evidence that there is at least some overlap between those neural systems acted
      upon by cannabinoids and those that are believed to be involved in incentive
      properties associated with other drugs of abuse.

PMID- 12213530
TI  - Behavioral effects of aminochrome and dopachrome injected in the rat substantia
      nigra.
AB  - The exact mechanism of cell death in neurodegenerative diseases remains obscure,
      although there is evidence that their pathogenesis may involve the formation of
      free radicals originating from the oxidative metabolism of catecholamines. The
      purpose of this study was to evaluate the degree of neurodegenerative changes and
      behavioral impairments induced by unilateral injection into the rat substantia
      nigra of cyclized o-quinones, aminochrome and dopachrome, derived from oxidizing
      dopamine and L-DOPA, respectively, with Mn(3+)-pyrophosphate complex. The
      behavioral changes were compared with those induced after selective lesions of
      dopaminergic neurons with 6-hydroxydopamine (6-OHDA). Intranigral injection of
      aminochrome and dopachrome produced impairment in motor and cognitive behaviors.
      The behavioral impairment was also revealed by apomorphine-induced rotational
      asymmetry. Apomorphine (0.5 mg/kg sc) significantly increased rotational behavior
      in rats injected with aminochrome and dopachrome. These rats presented a clear
      motor bias showing a significant contralateral rotation activity, similar but
      less vigorous that in rats injected with 6-OHDA. The avoidance conditioning was
      seriously impaired in rats injected with aminochrome and dopachrome although only
      dopachrome-injected rats showed a similar hypomotility to 6-OHDA-injected rats.
      The behavioral effects were correlated to the extent of striatal tyrosine
      hydroxylase (TH)-positive fiber loss. Rats receiving unilateral intranigral
      aminochrome and dopachrome injections exhibited a 47.9+/-5.1% and a 39.7+/-4.4%
      reduction in nigrostriatal TH-positive fiber density. In conclusion, this study
      provided evidence that oxidizing DA and L-DOPA to cytotoxic quinones, aminochrome
      and dopachrome appears to be an important mediator of oxidative damage in vivo.

PMID- 12213531
TI  - Effects of pentylenetetrazol-induced kindling of seizures on rat emotional
      behavior and brain monoaminergic systems.
AB  - The influence of pentylenetetrazol (PTZ)-induced kindling of seizures on the rat
      emotional behavior, the brain monoamine turnover rate measured in vitro, and
      correlation between behavioral and biochemical parameters, were examined in rats.
      The repeated administration of PTZ (35 mg/kg, ip) evoked kindled seizures in rats
      (Stage 4 or 5 of clonic-tonic convulsions-maximum). PTZ kindling caused selective
      changes in the rat emotional behavior, present in some models of anxiety only (a
      decreased freezing time in the conditioned freezing test and a decreased
      spontaneous and aversively conditioned ultrasonic vocalization). Simultaneously,
      PTZ kindling decreased the concentration of homovanillic acid (HVA) and 5
      hydroxyindoleacetic acid (5-HIAA) in the prefrontal cortex, decreased the DA
      (HVA/DA ratio) turnover rate in the striatum, and inhibited the serotonin (5-HT)
      metabolism (5-HIAA/5-HT ratio) in the hippocampus and the prefrontal cortex.
      Correlations between dopamine (DA) or 5-HT regional metabolic rates in brain
      structures and animal behavior were either abolished or reversed in PTZ-kindled
      animals. It is concluded that both DA and 5-HT systems contribute to the
      emotional effects of PTZ-induced kindling of seizures. The hypothesis is put
      forward that PTZ kindling-induced inhibition of the serotonergic innervation may
      lead to the compensatory increase in 5-HT(1A) receptors in the dentate gyrus of
      the hippocampus, thus evoking the anxiolytic-like changes in animal behavior.

PMID- 12213532
TI  - Age-related changes in the antinociception induced by taurine in mice.
AB  - Taurine is a nonessential amino acid that is of medical interest for the
      nutrition of infants. Taurine has been found in the central nervous system of
      rodents and humans, and among its potential therapeutic uses, it is interesting
      to remark its analgesic actions. It is also well known that concentration levels
      during the fetal and prenatal periods are higher than in adulthood. The data
      obtained so far indicate that taurine is involved in the development process of
      the brain and possibly other organs. The taurine levels in old age are still
      unknown, but it is presumed that they will be different from those of younger
      animals. Data about age-related alterations and functional modifications of this
      and other amino acids are still scarce. The aim of the present work was to study
      the antinociceptive effect of taurine and its relationship with aging in mice. No
      differences were found between prepubertal and young adult animals; on the
      contrary, old animals showed significantly reduced sensitivity to the
      antinociception induced by taurine; in fact, at the tested doses, taurine did not
      induce antinociception in this group of mice. The mechanism underlying this
      effect has not been clarified because there are several mechanisms and
      neurotransmitter systems involved in the antinociception induced by taurine.

PMID- 12213533
TI  - Dopamine antagonists during parturition disrupt maternal care and the retention
      of maternal behavior in rats.
AB  - Brief contact with pups at parturition enables the female rat to establish and
      retain the full repertoire of maternal behaviors, allowing her to respond rapidly
      to pups in the future. To determine whether the dopamine system is involved in
      the retention of maternal behavior, females were continuously infused with
      dopamine antagonists during the periparturitional period and then allowed either
      a brief interaction period with pups (3 h) or no interaction with pups (pups
      removed as they were born). Females were exposed to either the D1-like antagonist
      SCH 23390 (0.1 or 1.0 mg/kg/day) or the D2-like antagonist clebopride (0.5 or 1.0
      mg/kg/day). The high dose of either DA antagonist resulted in significant
      attenuation of maternal care immediately postpartum. When tested for the
      retention of maternal behavior 7 days later, however, only the females exposed to
      the D2 antagonist displayed a delayed response to shown full maternal behavior
      (FMB) towards donor pups. Thus, while both dopamine receptor subtypes appear
      necessary for the full and rapid expression of maternal behavior during the early
      postpartum period, only the D2 receptor subtype appears to be involved in the
      retention of this behavior.

PMID- 12213534
TI  - Tolerance and sensitization to the locomotor-activating effects of cocaine are
      mediated via independent mechanisms.
AB  - Tolerance or sensitization to the locomotor-activating effects of cocaine occurs
      depending upon the treatment regimen that is used. When cocaine is injected on a
      daily basis, sensitization occurs, whereas continuously infused cocaine leads to
      tolerance. Male Sprague-Dawley rats were treated for 7 days with continuous
      cocaine (50 mg/kg/day) via subcutaneously implanted osmotic minipumps, after
      which the pumps were removed. Locomotor activity was measured for 1 h each day.
      Some rats were challenged with an injection of cocaine (7.5, 15 or 30 mg/kg)
      either 2 or 9 days after pump removal. Two days after the pumps were removed (Day
      10), there were no significant differences between cocaine- or saline-treated
      rats in the amount of locomotor activity produced by the challenge injections.
      However, cocaine-treated rats challenged with cocaine 9 days after pumps were
      removed (Day 17) exhibited significant tolerance, as evidenced by a shift
      downward of the cocaine curve, as compared to saline controls. When the rats were
      injected again on the next day (Day 18), the activity levels of both groups
      increased, as compared to the effects observed on Day 17. Thus, although the
      cocaine-treated rats were still tolerant compared to the saline-treated rats,
      they were sensitized compared to their previous response to a challenge
      injection. These findings indicate that tolerance and sensitization to the
      locomotor-activating effects of cocaine can exist simultaneously, which suggests
      that they are mediated by separate mechanisms.

PMID- 12213535
TI  - Pharmacokinetic differences of morphine and morphine-glucuronides are reflected
      in locomotor activity.
AB  - The main metabolites of morphine, morphine-3-glucuronide (M3G) and morphine-6
      glucuronide (M6G), have been considered to participate in some of the effects of
      morphine. There is limited knowledge of the pharmacokinetics and dynamics of
      morphine and the main metabolites in mice, but mice are widely used to study both
      the analgesic effects and the psychomotor effects of morphine. The present study
      aimed to explore pharmacokinetic differences between morphine and morphine
      glucuronides in mice after different routes of administration, and to investigate
      how possible differences were reflected in locomotor activity, a measure of
      psychostimulant properties. Mice were given morphine, M3G or M6G by different
      routes of administration. Serum concentrations versus time curves,
      pharmacokinetic parameters and locomotor activity were determined.
      Intraperitoneal administration of morphine reduced the bioavailability compared
      to intravenous and subcutaneous administration, but not so for morphine
      glucuronides. The two morphine-glucuronides had similar pharmacokinetics, but
      morphine demonstrated higher volume of distribution and clearance than morphine
      glucuronides. The present results demonstrated no locomotor effect of M3G, but a
      serum concentration effect relationship for morphine and M6G. When serum
      concentrations and effect changes were followed over time, there was some right
      hand shifts with respect to locomotor activity, especially during the declining
      phase of the concentration curve and particularly for M6G.

PMID- 12213536
TI  - A comparative study in rodents of standardized extracts of Bacopa monniera and
      Ginkgo biloba: anticholinesterase and cognitive enhancing activities.
AB  - Bacopa monniera and Ginkgo biloba are well-known cognitive enhancers in Indian
      and Chinese traditional medicine systems. Standardized extracts of B. monniera
      and G. biloba were used to evaluate the antidementic and anticholinesterase
      activities in adult male Swiss mice. Antidementic activity was tested against
      scopolamine (3 mg/kg ip)-induced deficits in passive avoidance test. Three
      different extracts of B. monniera (30 mg/kg) and extract of G. biloba (15, 30 and
      60 mg/kg) were administered postoperatively, daily for 7 days and 60 min after
      the last dose, i.e., on Day 7, first trial was conducted. In passive avoidance
      test, increased transfer latency time (TLT) and no transfer response (NTR) were
      taken as criteria for learning. TLT and NTR were significantly increased and
      decreased in second trial, 24 h after the first trial in control group and
      scopolamine-dementia group, respectively. The B. monniera- and G. biloba-treated
      groups produced significant increase in TLT and NTR on second trial (40-80%)
      after scopolamine treatment, thus, attenuating its antidementic effect. Both the
      extracts showed a dose (10-1000 microg)-dependent inhibitory effect on
      acetylcholinesterase (AChE) activity (in vitro), performed
      spectrophotometrically. IC(50) of G. biloba was 268.33 microg, whereas none of
      the extracts of B. monniera showed more than 50% inhibition. At a dose
      concentration of 30 and 60 mg/kg, extracts of G. biloba showed a cognitive
      enhancing property and, at the same time, a significant decrease in AChE-specific
      activity in both per se and scopolamine-dementia groups. These extracts possess a
      significant anticholinesterase and antidementic properties, which may be useful
      in the treatment of dementia.

PMID- 12213537
TI  - Nicotinamide therapy protects against both necrosis and apoptosis in a stroke
      model.
AB  - BACKGROUND AND PURPOSE: Nicotinamide protects against brain damage in ischemia
      reperfusion. However, the dosage and time of treatment require clarification. It
      is also not clear if nicotinamide can protect against both necrosis and
      apoptosis. METHODS: Dose-response and time-effect studies were designed.
      Transient focal cerebral ischemia was induced by middle cerebral artery occlusion
      (MCAO) for 90 min. Different doses of nicotinamide were injected upon
      reperfusion. In time-effect studies, 500 mg/kg nicotinamide was administered at
      different times after the onset of reperfusion. Neurological finding scores were
      recorded. Infarct volumes were measured. RESULTS: In contrast to controls,
      neurological deficit scores and infarct volumes were greatly reduced by treatment
      with nicotinamide. The ED(50) of nicotinamide was 239+/-79 mg/kg (P=.95). It was
      found that nicotinamide injected during the first 6 h of reperfusion could
      effectively inhibit the development of brain damage. The optimal dose of
      nicotinamide was 500 mg/kg and gave a maximal response. CONCLUSIONS: Poly(ADP
      ribose) polymerase (PARP) plays a key role in DNA repair in stroke. Excessive
      PARP activity consumes NAD leading to energy depletion and neuronal damage. As an
      inhibitor of PARP, nicotinamide promotes the supply of energy. The results
      suggest that early application of nicotinamide at a suitable dosage significantly
      ameliorates necrotic and apoptotic brain injury after focal ischemia-reperfusion.

PMID- 12213539
TI  - Neonatal toluene exposure selectively alters sensitivity to different
      chemoconvulsant drugs in juvenile rats.
AB  - Toluene is an abused solvent widely used in several commercial products. Recent
      evidence indicates that this solvent is a noncompetitive inhibitor of N-methyl-D
      aspartate (NMDA) receptors and enhances gamma-aminobutyric acid(A) (GABA(A))
      receptor-mediated synaptic currents. Since NMDA and GABA(A) receptors have been
      implicated in seizures, this study investigated whether toluene exposure during
      synaptogenesis period alters the NMDA and GABA(A) receptor-mediated seizure
      susceptibility in juvenile rats. Neonatal rats were administered toluene (1 g/kg
      ip) daily over postnatal days (PN) 4-9. Rats were administered NMDA (10 mg/ml),
      picrotoxin (2 mg/ml), pentylenetetrazol, (5 mg/ml) and 4-aminopyridine (4-AP; 2
      mg/ml) via timed tail vein infusion on PN 34-36. Toluene exposure increased
      sensitivity to NMDA, picrotoxin and pentylenetetrazol, but did not affect 4
      aminoyridine-induced seizures in both male and female rats. These results suggest
      that toluene may possess a risk to the developing brain by inducing a long-term
      alteration in the function of NMDA and GABA(A) receptors.

PMID- 12213538
TI  - Interactions between the CB1 receptor agonist Delta 9-THC and the CB1 receptor
      antagonist SR-141716 in rats: open-field revisited.
AB  - This study examined the effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC)
      and the CB1 antagonist SR-141716 on open-field behaviors in male Sprague-Dawley
      rats. Animals were examined after administration of Delta(9)-THC alone (dose
      range: 0.3-5.6 mg/kg), SR-141716 alone (dose range: 1-5.6 mg/kg) and the two
      drugs in combination; injections were given intraperitoneally 30 min prior to
      testing. There was a dose-related suppression of ambulation (horizontal activity)
      and rearing (vertical activity) after Delta(9)-THC administration. Co
      administration of SR-141716 counteracted this suppression; however, antagonism
      was only partial for rearing. Interestingly, 1 mg/kg SR-141716 was as effective
      as 3 and 5.6 mg/kg SR-141716 in this antagonist action. Increasing doses of
      Delta(9)-THC produced an increase in circling behavior; latency to leave the
      starting area in the center of the field was significantly elevated by 5.6 mg/kg
      Delta(9)-THC. Those effects were completely blocked by SR-141716. Grooming and
      scratching showed a dose-related increase following administration of SR-141716
      (1-5.6 mg/kg), which were only partially blocked by co-administration of Delta(9)
      THC (3 and 5.6 mg/kg). When given alone, only the highest dose of SR-141716 (5.6
      mg/kg) depressed ambulation; rearing and latency were not significantly changed,
      and circling was absent. Differences in the number of vocalizations, urination
      and defecation generally did not differ clearly among the treatment conditions.
      These results may show that SR-141716 is acting as (i) an inverse agonist and/or
      (ii) that the endogenous cannabinoid system is tonically active under certain
      conditions.

PMID- 12213540
TI  - Prepulse inhibition in rats with temporary inhibition/inactivation of ventral or
      dorsal hippocampus.
AB  - Prepulse inhibition (PPI) of the acoustic startle response is a measure of
      sensorimotor gating and is decreased in neuropsychiatric diseases, including
      schizophrenia. Hippocampal involvement in PPI has been the subject of several
      studies, in particular, as aberrant hippocampal activity has been associated with
      schizophrenia. In rats, chemical stimulation of the ventral hippocampus reduced
      PPI, while normal PPI was found following hippocampal lesions, suggesting that
      ventral hippocampal overactivity is detrimental for PPI, but that normal
      hippocampal activity does not contribute substantially to PPI. In the present
      study, we investigated the importance of hippocampal activity for PPI by
      examining PPI in Wistar rats with temporarily decreased hippocampal activity,
      aiming to avoid compensatory processes that may occur with permanent lesions.
      Bilateral ventral or dorsal hippocampal infusions of the gamma-aminobutyric acid
      A (GABA(A)) receptor agonist muscimol (1 microg/side) or the sodium-channel
      blocker tetrodotoxin (TTX, 10 ng/side) reduced PPI. This reduction is probably
      neuroleptic-resistant since haloperidol and clozapine did not antagonize the
      muscimol-induced decreases in PPI. PPI reduction by muscimol inhibition or TTX
      inactivation of the dorsal or ventral hippocampus indicates that hippocampal
      activity contributes to sensorimotor gating, suggesting intact PPI after
      permanent hippocampal lesions to reflect compensatory processes. The data are
      discussed with respect to hippocampal dysfunction in schizophrenia.

PMID- 12213541
TI  - Effect of imipramine on the expression and acquisition of morphine-induced
      conditioned place preference in mice.
AB  - The effect of imipramine and alpha-adrenoceptor agonists and antagonists on the
      acquisition or expression of morphine-induced conditioned place preference (CPP)
      was studied in mice. An unbiased CPP paradigm was used to study the effect of the
      agents. In the first set of experiments, the drugs were used during the
      development of CPP by morphine or they were used alone in order to see if they
      induce CPP or conditioned place aversion (CPA). Our data showed that
      intraperitoneal injection of morphine sulphate (2.5-10 mg/kg) induced CPP in
      mice. Imipramine (0.5-2.5 mg/kg), phenylephrine (0.5-2 mg/kg), yohimbine (0.5-2
      mg/kg) or prazosin (0.1-1 mg/kg) did not influence CPP, but clonidine (0.002-0.05
      mg/kg) induced CPA. Yohimbine increased, while clonidine and prazosin reversed,
      morphine-induced CPP. Phenylephrine did not influence the CPP induced by
      morphine. In the second set of experiments, when the drugs were used before
      testing on Day 6, in order to test their effects on the expression of morphine
      induced CPP, imipramine (0.5-5 mg/kg) reversed morphine-induced CPP and this
      reversal was blocked by naloxone (2 mg/kg). Clonidine and prazosin reversed,
      while yohimbine decreased morphine-induced CPP. Phenylephrine did not alter the
      morphine response. Furthermore, yohimbine and prazosin reversed the imipramine
      effect. None of the drugs influenced locomotion. However, prazosin or yohimbine
      in combination with morphine altered locomotor activity during the acquisition of
      CPP. Yohimbine by itself increased locomotion. It is concluded that imipramine
      can induce CPA through an opioid receptor mechanism and alpha-adrenoceptor agents
      may influence morphine CPP.

PMID- 12213542
TI  - Hormone-like behavioral effects of levonorgestrel and its metabolites in the male
      rat.
AB  - Levonorgestrel (LNG), a contraceptive progestin, exhibits, besides its
      progestational activity, other hormone-like effects at the peripheral level. To
      assess whether LNG and its metabolites exert androgenic and/or estrogenic actions
      at the central nervous system (CNS), their effects on male sexual behavior in
      castrated rats were examined. LNG, 5alpha-dihydro LNG (5alphaLNG), and the
      3alpha,5alpha- and 3beta,5alpha-tetrahydro derivatives of LNG (3alphaLNG and
      3betaLNG, respectively) were administered for 3 weeks either alone (1000
      microg/day) or in combination (300 microg/day) with 5alpha-dihydrotestosterone
      (DHT, 300 microg/day) or with estradiol-17beta (E(2), 5 microg/day). Copulatory
      behavior was assessed twice per week and sex accessory organs weights recorded at
      the end of treatments. LNG restored full copulatory behavior comparable to that
      of testosterone treated animals, although with a slight delay, whereas 5alphaLNG
      induced male sexual behavior in a significantly lower number of subjects.
      3betaLNG and 3alphaLNG induced mounting but failed to restore intromission and
      ejaculation. Combined LNG+E(2) treatment fully activated mounting and
      intromission, but ejaculation was only partially restored. Combined
      5alphaLNG+E(2) treatment and the combinations of 3alphaLNG or 3betaLNG with E(2)
      were significantly less effective, activating fewer intromissions and
      ejaculations. 3alphaLNG and 5alphaLNG, in combination with DHT, restored male
      sexual behavior. LNG, but not its metabolites, induced a significant increase on
      the weight of sex accessory organs. The overall results demonstrated that high
      doses of LNG induce a potent androgen agonistic behavioral effect and that its A
      ring reduction diminishes this potency and enables a shift towards a weak
      estrogen-like effect.

PMID- 12213543
TI  - Anxiolytic effects of ethanol and phenobarbital are abolished in test-experienced
      rats submitted to the elevated plus maze.
AB  - Prior test experience compromises the anxiolytic efficacy of benzodiazepines
      (BZs) either in rats or mice, a phenomenon not exclusive to the elevated plus
      maze (EPM) animal model of anxiety, which is referred to as "one-trial
      tolerance." However, it remains to be determined whether a similar event occurs
      when testing other drugs that also possess binding-sites on the GABA(A) receptor,
      such as ethanol and barbiturates. In the present study, we have addressed this
      issue using maze-naive and maze-experienced (free exploration of the EPM 48 h
      earlier for 5 min) rats pretreated with ethanol (1.0-1.4 g/kg) or phenobarbital
      (20-60 mg/kg) and submitted to the EPM. The results confirmed the anxiolytic
      profile of both drugs, represented by increased open arm exploration and
      decreased risk assessment behavior, in maze-naive rats. However, in maze
      experienced rats, neither ethanol nor phenobarbital anxiolytic effects were
      observed, suggesting that prior maze experience compromised the drugs' anxiolytic
      activity. Thus, the "one-trial tolerance" phenomenon might also be extended to
      other drugs that bind to the GABA(A) receptor complex.

PMID- 12213544
TI  - Stress-induced subsensitivity to modafinil and its prevention by corticosteroids.
AB  - Brain alpha(1)-adrenoceptors are known to be necessary for motor activity in
      rodents and have been shown to be altered by stress and corticosteroids but only
      in biochemical experiments. To determine if the behaviorally coupled receptors
      are also affected by stress, the present study examined the effect of stress and
      corticosteroids treatment on the motor activity response to modafinil, a putative
      alpha(1)-adrenoceptor agonist, which is unique in that it elicits extremely high
      levels of activity via these receptors. Mice were subjected to various schedules
      of restraint stress for 1-6 days and were subsequently tested for either
      modafinil-induced or dopaminergically induced behavioral activity in the home
      cage using videotape recording. In experiments on corticosteroid treatment, mice
      received exogenous corticosterone or dexamethasone in the drinking water before
      and during the stress and were tested for modafinil-induced activity as above. It
      was found that the stress significantly reduced the response to the drug by the
      third daily session. Motor responses to dopaminergic agents including
      apomorphine, amphetamine, dihydrexidine and quinpirole were either not altered or
      were increased at this time. Treatment of animals with corticosterone or
      dexamethasone prior to and during stress prevented the behavioral subsensitivity
      to modafinil. Corticosterone pretreatment markedly suppressed the plasma
      corticosterone response to the stress. The present results provide further
      support for the hypothesis that stress produces a selective desensitization or
      inhibition of motor-related brain alpha(1)-adrenoceptors and that this effect can
      be prevented by corticosteroid treatment.

PMID- 12213545
TI  - The effect of serotonin and serotonin receptor antagonists on motion sickness in
      Suncus murinus.
AB  - In the present study, we investigated the effect of 5-hydroxytryptamine (5-HT)
      and 5-HT receptor agonists and antagonists on motion sickness in Suncus murinus,
      and the possibility that the emetic stimulus of 5-HT can alter the sensitivity of
      the animals to the different emetic stimulus of motion sickness. 5-HT (1.0, 2.0,
      4.0 and 8.0 mg/kg ip) induced emesis and that was antagonised by methysergide
      (1.0 mg/kg ip), the 5-HT(4) receptor antagonist sulphamate[1-[2
      [(methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl-5-fluoro-2-methoxy-1H-indole
      3-carboxylate (GR125487D; 1.0 mg/kg ip) and granisetron (0.5 mg/kg ip).
      Pretreatment with 5-HT caused a dose-related attenuation of the emetic response
      induced by a subsequent motion stimulus, which was not significantly modified by
      methysergide, granisetron or GR125487D pretreatment. (+)-1-(2,5-Dimethoxy-4
      iodophenyl)-2-amino-propane (DOI; 0.5 and 1.0 mg/kg ip), 8-hydroxy-2(di-n
      propylamino)tetralin (8-OH-DPAT; 0.1 mg/kg ip) but not methysergide, GR125487D or
      granisetron, attenuated motion-induced emesis, and that was not affected by
      pretreatment with ketanserin (2.0 mg/kg, ip) or N-[2-[4-(2-methoxyphenyl)-1
      piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrocholoride (WAY
      100635; 1.0 mg/kg ip), respectively. Indeed, ketanserin alone (0.1, 0.3, 1.0 and
      2.0 mg/kg ip) attenuated motion sickness. These data indicate that 5-HT(1/2), 5
      HT(3) and 5-HT(4) receptors are involved in the induction of 5-HT-induced emesis.
      However, agonist action at the 5-HT(1A/7) and 5-HT(2) receptors, and antagonist
      action at the 5-HT(2A) receptors can attenuate motion sickness in S. murinus.

PMID- 12213546
TI  - The Sam and Ann Barshop Center for Longevity and Aging Studies: the University of
      Texas Health Science Center at San Antonio.
AB  - The Sam and Ann Barshop Center for Longevity and Aging Studies is a focal point
      for advanced research designed exclusively to study the genes involved in aging
      and the diseases of aging. The research performed at the Barshop Center is based
      on a solid foundation of nearly twenty-five years of aging research at The
      University of Texas Health Science Center at San Antonio. Internationally
      recognized scientists in aging are now leading innovative research programs using
      state-of-the-art technologies in molecular and cellular biology to explore aging
      processes at the gene level in the four major programs that comprise the research
      at the Barshop Center: the Cellular Aging Program, the Invertebrate Aging
      Program, the Rodent Models of Aging Program, and the Human Genetics of Aging
      Program. The researchers involved in these programs share a common purpose in an
      atmosphere of collaboration to gain the scientific insights necessary to
      understand the molecular basis of aging. Their long-term goal is to gain the
      knowledge that will give rise to the development of interventions that retard or
      arrest the debilitating conditions associated with aging. February or March 2003
      marks the groundbreaking for the first building of Barshop Center's new stand
      alone facility. This is the initial step toward a $70 million, world-class
      research complex dedicated to the study of aging and healthy longevity.

PMID- 12213547
TI  - Do age-associated changes in 'physiologic' autoantibodies contribute to
      infection, atherosclerosis, and Alzheimer's disease?
AB  - More than 25 years ago, Pierre Grabar proposed that the age-associated increase
      in serum autoantibodies reflected a homeostatic function of the immune system
      that defended the internal milieu by targeting senescent molecules and cells for
      elimination. This mini-review examines recent evidence that autoantibodies may
      influence the risk of the elderly developing infectious, atherosclerotic, or
      Alzheimer's disease. Auto-anti-idiotypic antibodies suppress the antibody
      response to the nominal antigen and, thus, may contribute to the increased risk
      of infection and poor response to vaccines in the elderly. In contrast, low
      levels of autoantibodies to oxidised low-density lipoproteins or to the amyloid
      beta peptide may contribute to the increased risk of developing atherosclerosis
      of Alzheimer's disease, respectively.

PMID- 12213548
TI  - Molecular mechanisms of androgenetic alopecia.
AB  - Androgenetic alopecia (AGA) is hereditary and androgen-dependent, progressive
      thinning of the scalp hair that follows a defined pattern. While the genetic
      involvement is pronounced but poorly understood, major advances have been
      achieved in understanding principal elements of the androgen metabolism involved:
      androgen-dependent processes are predominantly due to the binding of
      dihydrotestosterone (DHT) to the androgen receptor (AR). DHT-dependent cell
      functions depend on the availability of weak androgens, their conversion to more
      potent androgens via the action of 5 alpha-reductase, low enzymatic activity of
      androgen inactivating enzymes, and functionally active AR present in high
      numbers. The predisposed scalp exhibits high levels of DHT, and increased
      expression of the AR. Conversion of testosterone to DHT within the dermal papilla
      plays a central role, while androgen-regulated factors deriving from dermal
      papilla cells are believed to influence growth of other components of the hair
      follicle. Current available treatment modalities with proven efficacy are oral
      finasteride, a competitive inhibitor of type 2 5 alpha-reductase, and topical
      minoxidil, an adenosine-triphosphate-sensitive potassium channel opener which has
      been reported to stimulate the production of vascular endothelial growth factor
      in cultured dermal papilla cells. Since the clinical success rate of treatment of
      AGA with modulators of androgen metabolism or hair growth promoters is limited,
      sustained microscopic follicular inflammation with connective tissue remodeling,
      eventually resulting in permanent hair loss, is considered a possible cofactor in
      the complex etiology of AGA.

PMID- 12213549
TI  - The aging bladder--a significant but underestimated role in the development of
      lower urinary tract symptoms.
AB  - There are three major areas in which bladder dysfunction causes considerable
      losses in quality of life: detrusor instability, impaired detrusor function and
      detrusor reaction on bladder outlet obstruction. Considerable changes in detrusor
      morphology, detrusor innervation and bladder metabolism are seen with aging and
      obstruction. This causes dysfunction and lower urinary tract symptoms. The
      relation between aging per se and external influence on the detrusor from
      diseases in the nervous system, in the vascular supply and in the lower urinary
      tract itself is poorly understood. To improve our ability to prevent and treat
      these conditions we need more insight in these pathophysiological conditions.

PMID- 12213550
TI  - The development of benign prostatic hyperplasia by trans-differentiation of
      prostatic stromal cells.

PMID- 12213551
TI  - Demethylation of classical satellite 2 and 3 DNA with chromosomal instability in
      senescent human fibroblasts.
AB  - Demethylation of genomic 5-methylcytosine is reported in aged human tissues and
      senesced human cells, although it is not understood to what extent this
      phenomenon contributes to replicative senescence. We examined methylation status
      of satellite 2 and 3 sequences during passages of normal human fibroblasts. These
      sequences are abundant in the juxtacentromeric heterochromatin of human
      chromosomes 1, 9 and 16, and heavily methylated in tissues of normal individuals.
      The decrease in DNA methylation level was two times faster in satellite 3 DNA
      than in satellite 2 and total DNA. Then we monitored appearance of micronuclei
      during the passages since they are indicative of heterochromatin decondensation
      or chromosome breakage. Concomitant with the DNA demethylation, micronuclei
      containing the heterochromatin of chromosomes 1, 9 or 16, appeared specifically.
      These results suggest that demethylation of heterochromatin has a role in
      replicative senescence through chromosome instability.

PMID- 12213552
TI  - Ageing is reversed, and metabolism is reset to young levels in recovering dauer
      larvae of C. elegans.
AB  - The nematode Caenorhabditis elegans responds to unfavourable environmental
      conditions by arresting development and entering diapause as a dauer larva.
      Dauers can survive several times the normal life span and the duration of the
      dauer state has no effect on postdauer life span. This led to the suggestion that
      dauers are non-ageing, and that dauers eventually perish as the consequence of
      depletion of stored nutrients. We have investigated physiological changes
      associated with long-term diapause survival, and found that dauer larvae slowly
      develop senescence-like symptoms, including decrease of metabolic capacity,
      aconitase enzyme activity, and ATP stores, and increase of lipofuscin- and
      oxidised flavin-specific fluorescence. However, these changes are reversed when
      the dauers recover. Thus senescence can occur before attainment of reproductive
      maturity, and furthermore, is reversible. Other life processes, including
      respiration rate and heat output, remain unaltered over four weeks of diapause at
      24 degrees C. Possible determinants of the enhanced life maintenance include
      increased resistance to oxidative stress provided by enhanced superoxide
      dismutase and catalase activities, and a shift to a highly reducing redox status.

PMID- 12213553
TI  - Distinct roles of processes modulated by histone deacetylases Rpd3p, Hda1p, and
      Sir2p in life extension by caloric restriction in yeast.
AB  - Caloric restriction has been demonstrated to extend life span and postpone aging
      in a variety of species. The recent extension of the caloric restriction paradigm
      to yeast places the emphasis of the search for the longevity effectors at the
      cellular level. To narrow the range of potential effectors of the caloric
      restriction response, we have examined the effects of the histone deacetylases
      Rpd3p, Hda1p, and Sir2p, which have distinguishable but partially overlapping
      influences on global patterns of gene expression, on the life extension afforded
      by caloric restriction. Deletion of the RPD3 gene extended life span, and there
      was no additive effect of caloric restriction. Deletion of HDA1 had no effect of
      its own on longevity but acted synergistically with caloric restriction to
      increase life span. SIR2 deletion shortened life span but did not prevent
      extension of life span by caloric restriction. The results suggest that Rpd3p
      affects both processes that play an obligate and those that play a synergistic
      role in life extension by caloric restriction, while Hda1p and Sir2p affect
      processes that are not the obligate longevity effectors of caloric restriction
      but instead synergize with them, although in opposite directions. From the known
      patterns of gene expression elicited by rpd3delta, hda1delta, and sir2delta, we
      propose that the major longevity effectors of caloric restriction in yeast
      involve carbohydrate/energy metabolism and mitochondrial function.

PMID- 12213554
TI  - Age-associated alteration of lipid peroxidation and superoxide dismutase activity
      in CBA and AKR mice.
AB  - Oxidative modification of lipids, proteins and DNA by reactive oxygen species in
      the organism and imbalance between the concentrations of free radicals and the
      antioxidant defenses may be related to processes such as aging and diseases
      (cardiovascular, neurodegenerative, cancer, etc.). Although the relationship
      between oxidant status and antioxidant defence in aging of different species,
      organs or sexes has been investigated extensively, the studies have produced
      conflicting results. In order to determine the extent of age-associated
      alteration, oxidant production and antioxidant status were measured in tissues of
      CBA and AKR mice of both sexes. At the same time we will focus on lipid
      peroxidation (LPO) process and superoxide dismutase activity (SOD) of AKR mice
      related to ontogeny of thymic lymphoma in mice of different age and sex. Male and
      female CBA and AKR mice aged 3, 6, 12 or 18 months were used. Lipid-bound sialic
      acid (LSA) content was determined as a malignancy marker. LPO processes of CBA
      and AKR mice were monitored according to the presence of thiobarbituric acid
      reactive substances (TBARS) in liver and thymus, and antioxidant status as SOD
      activity in whole blood. TBARS concentration increased significantly with age in
      the liver of CBA and AKR mice of both sexes, but only in male thymuses of both
      strains. TBARS concentration in female thymuses of both strains was unchanged
      during aging. Thus, age-associated LPO processes of tumor-free mice of both
      strains were tissue-dependent. In the liver of tumor-bearing CBA and AKR mice as
      well as in thymuses of AKR mice, TBARS concentration significantly decreased and
      was neither sex nor tissue related. SOD activity was strain-dependent but
      independent of sex. However, SOD activity in mice with developed thymomas was
      drastically reduced in comparison to tumor-free mice. Our data indicate that age
      associated LPO processes in both strains are only tissue-dependent and SOD
      activity mainly strain-dependent in tumor-free mice. In tumor-bearing mice LPO
      processes and SOD activity were not tissue, sex or strain dependent.

PMID- 12213555
TI  - Influence of aging and calorie restriction on MAPKs activity in rat kidney.
AB  - Mitogen-activated protein kinases (MAPK), which include the extracellular signal
      related kinases (ERK), the c-Jun N-terminal kinases (JNK), and the p38 MAPK, are
      important regulatory proteins by which a wide variety of extracellular signals
      are transduced into intracellular sites. Recent studies reported that mitogenic
      signal transduction in various cell types are exquisitely sensitive to reactive
      oxygen species (ROS) and the celluar redox status. In the present study, we
      investigated the activation of MAPK activity by aging and calorie restriction
      (CR) in rat kidneys isolated from Fischer 344 rats, ages 6, 12, 18, and 24 months
      fed ad libitum (AL) and CR diets. Results showed that the aging process strongly
      enhanced all three of the MAPK activities studied, ERK, JNK, and p38 MAPK, in
      parallel to increased ROS status. In contrast, we observed CR to markedly
      suppress the age-related activation of MAPKs. Based on these data, we concluded
      that an age-related increase in MAPK activity is associated with increased ROS,
      which was effectively suppressed by the anti-oxidative action of CR.

PMID- 12213556
TI  - Life spans and senescent phenotypes in two strains of Zebrafish (Danio rerio).
AB  - Zebrafish have become a widely used model organism in developmental biology
      research. In order to initiate an experimental foundation for aging studies, we
      have determined some basic gerontological parameters for populations of outbred
      zebrafish, and the golden sparse strain. Outbred zebrafish manifested a mean life
      span of about 42 months, with the longest living individual surviving for 66
      months. The golden sparse populations had a mean life span of 36 months and a
      maximum longevity of 58 months. Skeletal length at death increased with age,
      suggestive of indeterminate growth. A common age-related phenotype was spinal
      curvature. Radiographic analysis excluded bony changes as the cause of the spinal
      curvature, suggesting muscle abnormalities as a primary mechanism. These data and
      a growing abundance of related biological resources suggest that the zebrafish
      may be a compelling model organism for studies on aging.

PMID- 12213557
TI  - Antioxidant pathways in human aged skeletal muscle: relationship with the
      distribution of type II fibers.
AB  - Type II fiber loss and reactive oxygen species (ROS)-induced damage are hallmarks
      of muscle aging. The aim of this study was to analyze whether there exists a
      relationship between age-dependent changes in cellular antioxidant capacity and
      type II fiber loss in aged human skeletal muscles. Forty-five male and female
      subjects ranging in age from 65 to 90 year-old were divided into +40 and -40%
      type II fiber groups. We measured both total and Mn superoxide dismutase (total
      and MnSOD), glutathione peroxidase (GSHPx) and catalase (CAT) activities. We also
      measured the reduced and oxidized forms of glutathione (GSH and GSSG) and lipid
      peroxide (LPO) levels. Total SOD activity was lower in the -40% type II fiber
      group than in the +40% group; MnSOD tended to be lower but data are not
      statistically consistent. Both GSHPx and CAT activities remained unchanged; as
      did GSH, GSSG and GSH/GSSG ratio. Finally, muscle samples with -40% type II
      fibers had a significantly higher LPO content compared to those with +40% type II
      fibers. In summary, a relationship between human skeletal muscle aging, type II
      fiber loss and ROS reactions seems to exist.

PMID- 12213558
TI  - Thymic sensitivity to hypoxic condition in young and old rats. Age-dependent
      expression of NF-kappaB.
AB  - Oxygen keeps the entire enzymatic machinery in its physiological state.
      Senescence is associated with damage caused by oxidative stress, affecting also
      the immune system. In this study the effect of chronic hypoxia for 12 days on
      young and elderly rat thymus was investigated. The significant changes in cell
      thymic organization in young and old-aged rat thymus, with redistribution of
      thymic cells and stroma, were even more marked after prolonged hypoxia. These
      were further associated to down-regulation of NF-kappaB expression in young rats
      but up-regulation in old rats. Reorganization of thymic compartments together
      with disregulated expression of transcription factors, mainly expressed by
      'common' thymocytes, may be related to an altered function under hypoxic
      conditions, inducing opposite responses in young and aged thymuses, probably
      related to different states of basal oxidative stress.

PMID- 12213559
TI  - Expression of lymphocyte homing receptors alpha4beta7 and MAdCAM-l in young and
      old rats.
AB  - The elderly constitute the most rapidly growing subpopulation in the United
      States. This age group represents a significant burden on the healthcare system
      due, in part, to increases in morbidity and mortality associated with an increase
      in the incidence of intestinal infectious diseases. Our previous studies suggest
      that impaired homing of IgA immunoblasts from the Peyer's patches to the
      intestinal lamina propria contributes to the diminished intestinal immune
      response in the elderly. The present study employs flow cytometry and
      quantitative immunohistochemistry to assess age-related changes in the numbers of
      peripheral blood mononuclear cells expressing the homing integrin alpha4beta7 and
      vascular endothelial cells in the intestine expressing its specific receptor, the
      address in MAdCAM-1, in inbred Fischer 344 rats. The proportion of alpha4beta7
      positive mononuclear cells in young rats is significantly greater than that
      measured in the blood of senescent animals. Although the density of intestinal
      lamina propria blood vessels with MAdCAM-1-positive endothelium was greater in
      young adult rats in comparison to old animals, this difference achieved only
      borderline statistical significance. This is the first study to examine the
      expression of these two critical lymphocyte homing molecules as a function of
      age.

PMID- 12213560
TI  - Phenotype, antigen-presenting capacity, and migration of antigen-presenting cells
      in young and old age.
AB  - In the present paper, we investigated whether the phenotype, the antigen
      presenting capacity, and the migration of antigen-presenting cells (APCs), are
      affected by the aging process. APCs were obtained incubating peritoneal monocyte
      macrophage cells with granulocyte-macrophage colony-stimulating factor (GM-CSF)
      (immature APCs) or GM-CSF and IFNgamma (mature APCs). Phenotypically, after 8
      days incubation, APCs cultures were composed of CD11c and Mac-3 cells, with a
      similar representation, both in young and old mice. The absolute number and the
      expression of MHC I and II, CD80, and CD86 both on immature and mature APCs were
      not significantly different in young and old mice. APCs from old mice induced
      similar lymphocyte proliferative responses but lower lymphocyte cytotoxicity and
      a reduced number of CD8(+) T cells producing IFNgamma in comparison with APCs
      from young animals. Lymphocyte responses were antigen-specific, since TS/A pulsed
      APCs induced lymphocyte cytotoxicity against TS/A but not against syngeneic TUBO
      tumor cells. The low expression of the mRNA for the migratory CCR7 chemokine
      receptor present in immature APCs from old mice was greatly increased in mature
      APCs up to the levels found in APCs from young animals. The in vivo migration of
      APCs was higher in old than in young mice. These results demonstrate that some
      alterations in APCs function are present in aging, suggesting that an increased
      migratory capacity of old APCs may be required to balance their reduced antigen
      presentation to cytotoxic lymphocytes.

PMID- 12213561
TI  - Drop of connexin 43 in replicative senescence of human fibroblasts HEL-299 as a
      possible biomarker of senescence.
AB  - The expression of connexin 43 (cx43) and cell-cell communication were studied in
      replicative senescence of cultured HEL-299 fibroblasts. A progressive decrease in
      fluorescent dye transfer was detected by a scrape-loading technique in aging
      fibroblasts. This change was accounted for by a marked decrease in the amount of
      cx43 in aging cells, as detected by western blot analysis (cell extracts) and
      indirect fluorescence (cells in culture). However, semiquantitative RT-PCR assays
      of cx43 mRNA did not reveal appreciable changes, which suggests several possible
      explanations for the mechanism(s) underlying the decrease of cx43 in aging cells.
      These findings support the idea that the reduced expression of cx43 might be a
      biomarker of cell senescence.

PMID- 12213562
TI  - Five age-dependently expressed genes in mouse brain revealed by the fluorescence
      differential display-PCR technique.
AB  - We used a fluorescence differential display-PCR (FDD-PCR) technique to analyze
      the genes expressed in mouse brains collected at nine different developmental
      stages ranging from 3 days to 15 months after birth, and 5 age-dependently
      expressed genes were found. Age-dependent expression of each of these 5 genes was
      confirmed by quantitative real-time PCR analysis. Of the 5 genes, 4 (B1-B4) had
      high homology with the nucleotide sequences of cDNA clones of known mouse genes
      (myelin proteolipid protein, transferrin, embryo cDNA from the RIKEN full-length
      enriched library, and protein tyrosine phosphatase), and the rest (B5) with
      expressed sequence tags of an unknown gene. Sequencing analysis of the full
      length cDNA constructed based on the B5 sequence demonstrated that the gene
      product of B5 was identical to G-substrate, a specific substrate for cGMP
      dependent protein kinase. The expression patterns of known genes obtained in our
      study may provide a further opportunity to investigate the biological and
      physiological roles of the proteins they encode.

PMID- 12213563
TI  - Age-related changes in plasma orexin-A concentrations.
AB  - To study the effect of aging on orexin-A, we measured plasma orexin-A
      concentrations in 82 healthy volunteers (55 men and 27 women) over a wide range
      of ages (mean 50.2 +/- 13.9 years, ranging from 23 to 79 years). Correlation
      analyses revealed that plasma orexin-A concentrations correlated with age (r =
      0.50, P < 0.01). When comparing three age groups, it appeared that the
      concentrations in the group of more than 60 years were significantly higher than
      those in the group of less than 39 years in both genders (P < 0.05). These
      findings suggest that orexin-A could be involved in aging in a healthy
      population.

PMID- 12213564
TI  - Simple tools for forecasts of population ageing in developed countries based on
      extrapolations of human mortality, fertility and migration.
AB  - Suitable assumptions for the Gompertz mortality law take into account the break
      in the time development observed recently by Wilmoth et al. They show how a
      drastic reduction in the birth rate and improved living conditions lead to a
      drastic increase in the fraction of old people in the population, and how
      immigration of half a percent of the population per year can mostly stop this
      increase.

PMID- 12213565
TI  - 'Anti-aging' medicine: does it exist? A critical discussion of 'anti-aging health
      products'.
AB  - 'Anti-aging' medicine has become a popular topic, in the lay press, the (semi-)
      scientific literature and the Internet.(1) In almost all instances, claims of
      drugs, health supplements and other types of intervention are not based on any
      evidence supported by sound scientific knowledge. Specifically, the aging process
      itself, in contrast to age-related diseases, has so far neither been fully
      understood, nor significantly influenced in higher species, notably humans. In
      addition to the ill-defined effects, claims of anti-aging medicine also pose a
      considerable economic burden on the usually poorly informed older segment of the
      population. The present paper is based on a recent report by the United States
      General Accounting Office (GAO) on the questionable and even harmful effects of
      anti-aging health products for seniors.

PMID- 12213567
TI  - Fidelity and spatio-temporal control in MAP kinase (ERKs) signalling.
AB  - Extracellular signals transduced via receptor tyrosine kinases, G-protein-coupled
      receptors or integrins activate Ras, a key switch in cellular signalling.
      Although Ras can activate multiple downstream effectors (PI3K, Ral em leader )
      one of the major activated pathway is a conserved sequential protein kinase
      cascade referred to as the mitogen activated protein (MAP) kinase module:
      Raf>MEK>ERK. The fidelity of signalling among protein kinases and the spatio
      temporal activation are certainly key determinants for generating precise
      biological responses. The fidelity is ensured by scaffold proteins, a sort of
      protein kinase "insulators" and/or specific docking sites among the members of
      the signalling cascade. These docking sites are found in upstream and downstream
      regulators and MAPK substrates [Nat Cell Biol 2 2000 110]. The duration and the
      intensity of the response are in part controlled by the compartmentalisation of
      the signalling molecules. Growth factors promote nuclear accumulation and
      persistent activation of ERK (p42/p44 MAP kinases) during the entire G1 period
      with an extinction during S-phase. These features are exquisitely well controlled
      by (i) the temporal induction of the MAP kinase phosphatases, MKP1-3, and (ii)
      the compartmentalisation of the signalling molecules. We have shown that MKP1-2
      induction is strictly controlled by the activation of the MAP kinase module
      providing evidence for an autoregulatory mechanism. This negative regulatory loop
      was further enhanced by the capacity of ERK to phosphorylate MKP1 and 2. This
      action reduced the degradation rate of these MKPs through the ubiquitin
      proteasomal system [Science 286 1999 2514]. Whereas the two upstream kinases of
      the module, Raf and MEK remained cytoplasmic, ERK anchored to MEK in the
      cytoplasm of resting cells, rapidly translocated to the nucleus upon mitogenic
      stimulation. This process was rapid, reversible, and controlled by the strict
      activation of the MAPK cascade. Prevention of this nuclear translocation, by
      overexpression of a cytoplasmic ERK-docking molecule (inactive MKP3) prevented
      growth factor-stimulated DNA replication [EMBO J 18 1999 664]. Following long
      term stimulation, ERK progressively accumulated in the nucleus in an inactive
      form. This nuclear retention relied on the neosynthesis of short-lived nuclear
      anchoring proteins. Nuclear inactivation and sequestration was likely to be
      controlled by MAP kinase phosphatases 1 and 2. Therefore we propose that the
      nucleus represents a site for ERK action, sequestration and signal termination [J
      Cell Sci 114 2001 3433]. In addition, with the generation of mice invalidated for
      each of the ERK isoforms, we will illustrate that besides controlling cell
      proliferation the ERK cascade also controls cell differentiation and cell
      behaviour [Science 286 1999 1374].

PMID- 12213568
TI  - Antioxidants and oxidants regulated signal transduction pathways.
AB  - Many drugs and xenobiotics induce signal transduction events leading to gene
      expression of either pharmacologically beneficial effects, or unwanted side
      effects such as cytotoxicity which can compromise drug therapy. Using dietary
      chemopreventive compounds (isothiocyanates and green tea polyphenols), which are
      effective against various chemically-induced carcinogenesis models in animals
      studies, we studied the signal transduction events and gene expression profiles.
      These compounds have typically generated cellular "oxidative stress" and
      modulated gene expression including phase II detoxifying enzymes GST and QR as
      well as cellular defensive enzymes, heme oxygenase 1 (HO-1) and GST via the
      antioxidant/electrophile response element (ARE/EpRE). Members of the bZIP
      transcription factor, Nrf2 which heterodimerizes with Maf G/K, were found to bind
      to ARE, and transcriptionally activate ARE. Additionally the mitogen-activated
      protein kinases (MAPK; ERK, JNK and p38) were differentially activated by these
      compounds, and involved in the transcriptional activation of ARE-mediated
      reporter gene. Transfection studies with various cDNA encoding for wild-type of
      MAPK and Nrf2 showed synergistic response during co-transfection and to these
      agents. However, by increasing the concentrations of these xenobiotics, caspase
      activities and apoptosis were observed which were preceded by mitochondria damage
      and cytochrome c mitochondria release. Further, increased concentrations led to
      rapid cell necrosis. [corrected] Thus, we have proposed a model, that at low
      concentrations, these compounds activate MAPK pathway leading to activation of
      Nrf2 and ARE with subsequent induction of phase II and other defensive genes
      which protect cells against toxic insults thereby enhancing cell survival, a
      beneficial homeostatic response. At higher concentrations, these agents activate
      the caspase pathways, leading to apoptosis, a potential cytotoxic effect if it
      occurred in normal cells. The studies of these signaling pathways may yield
      important insights into the pharmacodynamic and toxicodynamic effects of drugs
      and xenobiotics during pharmaceutical drug discovery and development.

PMID- 12213569
TI  - Activation of mitogen-activated protein kinases (MAPKs) by aromatic hydrocarbons:
      role in the regulation of aryl hydrocarbon receptor (AHR) function.
AB  - The aromatic hydrocarbon (Ah) receptor (AHR) is the only known cellular receptor
      of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and of many other widespread
      environmental contaminants that cause diverse toxic effects in animals and
      humans. Most, if not all, the biological effects of TCDD are mediated by the
      activation of AHR, which is a ligand-activated transcription factor required for
      ligand-induced expression of several detoxification genes, including those
      encoding for cytochrome P450 enzymes CYP1A1, CYP1A2, and CYP1B1. Environmental
      agents also activate several mitogen-activated protein kinase (MAPK) pathways,
      believed to modulate transcription factor function and to regulate gene
      expression. However, the contribution to TCDD toxicity resulting from cross-talk
      between AHR and MAPK pathways has yet to be determined. In this study, we show
      that TCDD and other AHR ligands induced the immediate activation of the
      extracellular signal-regulated kinases and the Jun N-terminal kinases, but not
      the p38 MAPKs. MAPK activation by TCDD did not require the AHR, since it occurred
      equally well in AHR-negative CV-1 cells and in Ahr (-/-) mouse embryonic
      fibroblasts as in AHR-positive cells. Distinct from serum factors and the tumor
      promoter TPA-induced MAPKs, which resulted in transcriptional activation of ELK
      or c-JUN, TCDD-stimulated MAPKs were critical for the induction of AHR-dependent
      gene transcription and CYP1A1 expression. These data indicate that AHR ligands
      elicit AHR-independent non-genomic events that are essential for AHR activation
      and function.

PMID- 12213570
TI  - The c-Jun N-terminal kinases in cerebral microglia: immunological functions in
      the brain.
AB  - The c-Jun N-terminal kinases (JNKs) exert a pleiotrophy of physiological and
      pathological actions. This is also true for the immune system. Disruption of the
      JNK locus results in substantial functional deficits of peripheral T-cells. In
      contrast to circulating immune cells and the role of p38, the presence and
      function of JNKs in the immune cells of the brain remain to be defined. Here, we
      report on the expression and activation of JNKs in cultivated microglia from
      neonatal rats and from mice with targeted disruption of the JNK locus and the N
      terminal mutation of c-Jun (c-JunAA), respectively. JNK1, 2 and 3 mRNA and
      proteins were all expressed in microglia. Following stimulation with LPS (100
      ng/mL), a classical activator of microglia, JNKs were rapidly activated and this
      activation returns to basal levels within 4 hr. Following LPS and other stimuli
      such as thrombin (10-50 unit/mL), the activation of JNKs went along with the N
      terminal phosphorylation of c-Jun which persisted for at least 8 hr. Indirect
      inhibition of JNK by CEP-11004 (0.5-2 microM), an inhibitor of mixed-lineage
      kinases (MLK), reduced the LPS-induced phosphorylation of both, JNK and c-Jun, by
      around 50%, and attentuated the LPS-induced the alterations in microglial
      morphology. Finally, JNKs are involved in the control of cytokine release since
      both, incubation with CEP-11004 and disruption of the JNK1 locus enhanced the
      release of TNFalpha, IL-6 and IL-12. Our findings provide insight in so far
      unknown functions of JNKs in cerebral immune cells. These observations are also
      important for the wide spread efforts to develop JNK-inhibitors as
      neuroprotective drugs which, however, might trigger pro-inflammatory processes.

PMID- 12213571
TI  - Inflammatory signal transduction in Crohn's disease and novel therapeutic
      approaches.
AB  - Although signal transduction phenomena are well understood in vitro, their
      relevance for physiology and pathophysiology remains obscure. Recent years,
      however, have seen a plethora of attempts to link cell biochemistry and disease.
      At the Luxembourg conference it was attempted to link basal science to disease.
      In my presentation I focused on our research on stress activated kinases and
      other signalling elements in this respect in a variety of pro-inflammatory
      conditions. Knowledge of these pathways has now led to new therapeutic
      approaches, especially in Crohn's disease, which will be the subject of this
      commentary.

PMID- 12213572
TI  - Growth signaling in breast cancer cells: outcomes and promises of proteomics.
AB  - Methods in functional proteomics are now used to study the intracellular
      signaling pathways that underlie the development of breast cancer. As shown with
      fibroblast growth factor-2, the oncogenic/non-coding mRNA H19 and 14-3-3
      proteins, proteomics is a powerful approach to identify signaling proteins and to
      decipher the complex signaling circuitry involved in growth of breast cancer
      cells. Together with genomics, proteomics is now providing a way to define
      molecular processes involved in breast cancerogenesis and to identify new
      therapeutic targets.

PMID- 12213573
TI  - Divalent cations and the relationship between alphaA and betaA domains in
      integrins.
AB  - Integrins contain either one or two von Willebrand factor A-like domains, which
      are primary ligand and cation binding regions in the molecules. Here we examine
      the first structure of an A domain of a beta subunit, in alphanubeta3 and compare
      it to known A domain structures of alpha subunits. Ligand binding to immobilized
      alphanubeta3 domain is stimulated by Ca2+ rather than inhibited by it.
      Biochemical, cell biological and structural evidence suggests that the A domain
      is a major site of ligand interaction in alphanubeta3. The Arg-Gly-Asp based
      inhibitor cilengitide (EMD 121974) inhibites ligand interaction with
      transmembrane-truncated alphanubeta3 in the presence of either Ca2+ or Mn2+ ions,
      and does so with similar kinetics. The alphanubeta3 structure reveals that both
      the alphaA and betaA domains share common structural cores. But, in contrast to
      alphaA, the betaA domain has three cation binding sites, that are involved either
      directly or indirectly in ligand binding. Structural alignment of alphaA and
      betaA domains reveals additional loops unique only to the betaA domain and much
      evidence support that that these loops are important for ligand binding
      specificity and for the interaction between alpha and beta subunits. Since the
      position of these loops are evolutionary conserved but their primary sequence
      varies between the various betaA domains, they represents potential targets for
      dissecting functional diversity among integrins.

PMID- 12213574
TI  - A homogenous assay to monitor the activity of the insulin receptor using
      Bioluminescence Resonance Energy Transfer.
AB  - Insulin exerts its biological effects through a plasma membrane receptor that
      possesses a tyrosine kinase activity. Binding of insulin to its receptor induces
      a conformational change that stimulates the autophosphorylation of the receptor
      on tyrosine residues. This autophosphorylation stimulates the tyrosine kinase
      activity of the receptor toward intracellular substrates involved in the
      transmission of the signal. The discovery of pharmacological agents that
      specifically activate the tyrosine kinase activity of the insulin receptor will
      be of great importance for the treatment of insulin-resistant or insulin
      deficient patients. We have developed a procedure based on Bioluminescence
      Resonance Energy Transfer (BRET) to monitor the activation state of the insulin
      receptor. Human insulin receptor cDNA, was fused to either Renilla luciferase or
      yellow fluorescent protein coding sequences. Fusion insulin receptors were
      partially purified by wheat-germ lectin chromatography from HEK-293 cells co
      transfected with these constructs. The conformational change induced by insulin
      on its receptor could be detected as an energy transfer (BRET signal) between
      Renilla luciferase and yellow fluorescent protein. BRET signal paralleled insulin
      induced autophosphorylation of the fusion receptor. Dose-dependent effects of
      insulin, insulin-like growth factor 1 and epidermal growth factor on BRET signal
      were in agreement with known pharmacological properties of these ligands.
      Moreover, an antibody, which activated the autophosphorylation of the receptor,
      had similar effects on BRET signal. This methodology allows for rapid analysis of
      the effects of agonists on insulin receptor activity and could, therefore, be
      used in high-throughput screening for the discovery of molecules with insulin
      like properties.

PMID- 12213575
TI  - Identifying in vivo targets of cyclin-dependent kinase inhibitors by affinity
      chromatography.
AB  - Cyclin-dependent kinases (CDKs) regulate the cell division cycle, apoptosis,
      transcription, differentiation and many functions in the nervous system. The
      frequent deregulation of CDKs in cancers and in numerous other pathologies
      justifies the active search for chemical inhibitors capable of reversibly and
      selectively inhibiting this class of enzymes. Intensive screening of collections
      of natural and synthetic compounds has led to the identification of several
      families of ATP competitive CDK inhibitors. As the therapeutic potential of the
      most promising compounds is currently being evaluated in preclinical and clinical
      trials, their mechanism of action is still unclear. In particular, the real
      spectrum of their intracellular targets remains largely unknown. Determination of
      the selectivity of the compounds and identification of their intracellular
      targets constitute a prerequisite to understand their cellular effects and to
      improve their efficiency on a rational basis. The classical method for the
      determination of a compound's selectivity consists in testing the compound in a
      panel of purified kinases. However, the selectivity study is then restricted to
      the panel's enzymes. As a consequence, many, if not most other potential targets
      are not evaluated. As an alternative way to investigate the range of true targets
      of CDK inhibitors, we propose an affinity chromatography approach based on
      immobilized inhibitors. Briefly, the inhibitor is covalently bound to a resin and
      cellular extracts are batch loaded on this inhibitor matrix. After extensive
      washing, the bound proteins are resolved by SDS-PAGE and identified by
      microsequencing. In addition to confirming the interaction of CDK inhibitors with
      CDKs, this method has led to the identification of additional, sometimes
      unexpected, targets. We here illustrate the potential of this technique through a
      few examples.

PMID- 12213576
TI  - ErbB-2-induced mammary tumor growth: the role of cyclin D1 and p27Kip1.
AB  - The neu (c-erbB-2, HER2) proto-oncogene encodes a receptor tyrosine kinase that
      is a member of an important growth factor receptor family which includes the
      epidermal growth factor receptor (EGFR, ErbB1), ErbB3 and ErbB4. The neu is found
      over-expressed in 20-30% of human breast tumors. The c-erbB-2 is sufficient for
      the induction of mammary tumorigenesis in transgenic mice and the pathology of
      these mammary tumors strongly resembles human breast cancer. Murine transgenic
      models engineered to recapitulate human breast cancer provide an excellent and
      straightforward approach to dissect the molecular mechanisms governing the onset
      and progression of this disease. The molecular mechanisms by which ErbB-2
      transforms cells involves direct effects on components of the cell-cycle
      regulatory apparatus. Recent studies have demonstrated a key role for components
      of the cell-cycle, in particular cyclin D1 and p27Kip1 (p27) in the onset and
      progression of ErbB-2-induced murine mammary tumorigenesis. Such studies have
      provided further impetus to therapeutics targeting these cell-cycle proteins.

PMID- 12213577
TI  - Independent contribution of three different pathways to ultraviolet-B-induced
      apoptosis.
AB  - Ultraviolet-B radiation (UVB) causes a variety of biological effects which
      include the induction of apoptosis. UVB-induced apoptosis provides a well
      controlled scavenging mechanism protecting cells from malignant transformation.
      To induce programmed cell death, UVB uses a variety of cellular signaling
      pathways. In this context induction of nuclear DNA damage seems to be the
      predominant pathway, since experimental reduction of DNA damage was associated
      with a strong suppression of apoptosis. Additionally, UVB has been shown to
      target cytoplasmatically located or membrane bound components to induce signal
      transduction. UVB was found to directly activate cell surface death receptors,
      thereby triggering the apoptotic machinery. Furthermore, UVB-induced
      intracellular formation of reactive oxygen species (ROS) accompanied by
      mitochondrial dysfunction and cytochrome c release was demonstrated to be
      additionally involved in the apoptotic program. The following review will briefly
      discuss current aspects of the interplay between the different signaling pathways
      involved in UVB-induced apoptosis.

PMID- 12213578
TI  - Cell-specific regulation of apoptosis by glucocorticoids: implication to their
      anti-inflammatory action.
AB  - Glucocorticoids play a major role in attenuation of the inflammatory response.
      These steroid hormones are able to induce apoptosis in cells of the hematopoietic
      system such as monocytes, macrophages, and T lymphocytes that are involved in the
      inflammation reaction. In contrast, it was discovered recently that in glandular
      cells such as the mammary gland epithelia, hepatocytes, ovarian follicular cells,
      and in fibroblasts glucocorticoids protect against apoptotic signals evoked by
      cytokines, cAMP, tumor suppressors, and death genes. The anti-apoptotic effect of
      glucocorticoids is exerted by modulation of several survival genes such as Bcl-2,
      Bcl-x(L), and NFkB, in a cell-specific manner. Moreover, upregulation or
      downregulation of the same gene product can occur in a cell-dependent manner
      following stimulation by glucocorticoids. This phenomenon is probably due to
      composite regulatory cross-talk among multiple nuclear coactivators or
      corepressors, which mediate the transcription regulation of the genes, by their
      interaction with the glucocorticoid receptor. These observations suggest that the
      anti-inflammatory action of glucocorticoids is exerted by two complementary
      mechanisms: on one hand, they induce death of the cells that provoke the
      inflammation, and on the other hand they protect the resident cells of the
      inflamed tissue by arresting apoptotic signals. Moreover, the complementary
      action of glucocorticoids provides a new insight to the therapeutic potential of
      these hormones.

PMID- 12213579
TI  - Prospects for targeting the Bcl-2 family of proteins to develop novel cytotoxic
      drugs.
AB  - Over the last decade the molecular mechanisms controlling programmed cell death
      (apoptosis) have become clearer. It appears that many physiological and damage
      signals activate the cell death machinery by inhibiting the pro-survival Bcl-2
      proteins. Since many chemotherapeutic drugs used to treat cancers activate the
      cell death machinery indirectly, there is much interest in developing peptide and
      non-peptide mimics of the BH3-only proteins, a family of proteins that act as
      direct antagonists of Bcl-2, as novel anti-cancer agents. This commentary review
      current progress in our search for such drugs and discusses recent findings in
      light of our current understanding of the cell death signaling. The potential for
      discovering novel agents that may form a useful part of the treatment of
      malignant disease is enormous but we still lack critical understanding of
      precisely how Bcl-2 function. However, the frequency of mutations affecting
      proteins that (directly or indirectly) impinge on apoptosis suggests that the
      approach of targeting Bcl-2 might be a profitable one.

PMID- 12213580
TI  - Regulation of p53: intricate loops and delicate balances.
AB  - The p53 tumor suppressor protein provides a major anti-cancer defense mechanism,
      as underscored by the fact that the p53 gene is the most frequent target for
      genetic alterations in human cancer. Recent work has led to the realization that
      p53 lies at the hub of a very complex network of signaling pathways, which
      integrate a variety of intracellular and extracellular inputs. Part of this
      network consists of an array of autoregulatory feedback loops, where p53 exhibits
      very intricate interactions with other proteins known to play important roles in
      the determination of cell fate. We discuss two such loops, one involving the beta
      catenin protein and the other centering on the Akt/protein kinase B. In both
      cases, the central module is the interplay between p53 and the murine double
      minute 2 (Mdm2) protein, which inactivates p53 and targets it for rapid
      proteolysis. Whereas deregulated beta catenin can lead to Mdm2 inactivation and
      p53 accumulation, active p53 can promote the degradation and downregulation of
      beta catenin. Similarly, Akt can block p53 activation by potentiating Mdm2,
      whereas activated p53 can tune down Akt in several different ways. In each case,
      the actual output of the loop is determined by the delicate balance between the
      opposing effects of its different components. Often, this balance is dictated by
      additional signaling processes that occur simultaneously within the same cell.
      Genetic alterations characteristic of cancer are capable of severely distorting
      this balance, thereby overriding the tumor suppressor effects of p53 in a manner
      that facilitates neoplastic conversion.

PMID- 12213581
TI  - Identification of cytokine-induced nuclear factor-kappaB target genes in ovarian
      and breast cancer cells.
AB  - NF-kappaB is a pleiotropic transcription factor controlling the expression of
      many genes and viruses. NF-kappaB plays a role in immune response, cellular
      adhesion or acute phase response. It also inhibits apoptosis and favors cancer
      cell survival. We studied the expression of genes controlled by NF-kappaB in
      ovarian and breast adenocarcinoma cancer cells. We stably transfected OVCAR-3 and
      MCF7 A/Z cells with an expression vector coding for the mutated inhibitor
      IkappaBalpha, which sequesters NF-kappaB in the cytoplasm. We stimulated control
      and IkappaBalpha expressing cells with IL-1beta or TNF-alpha and extracted the
      RNA, which was reverse-transcribed and hybridized to DNA microarrays. Several of
      the genes identified were not known as NF-kappaB target genes. Among them, we
      confirmed the differential expression of ephrin-A1 and caveolin-1 by quantitative
      real-time polymerase chain reaction. Our results showed an NF-kappaB-dependent
      induction of ephrin-A1 and caveolin-1 mRNAs after stimulation with TNF-alpha and
      IL-1beta, confirming that NF-kappaB controls target genes implied in tumor
      angiogenesis and cell transformation.

PMID- 12213582
TI  - Nuclear factor-kappa B and cancer: its role in prevention and therapy.
AB  - Cancer is a hyperproliferative disorder in which invasion and angiogenesis lead
      to tumor metastasis. Several genes that mediate tumorigenesis and metastasis are
      regulated by a nuclear transcription factor, nuclear factor kappa B (NF-kappaB).
      A heterotrimeric complex consisting of p50, p65, and IkappaBalpha, NF-kappaB is
      present in its inactive state in the cytoplasm. When NF-kappaB is activated,
      IkappaBalpha is degraded and p50-p65 heterodimer is translocated to the nucleus,
      binds the DNA (at the promoter region), and activates gene. Research within the
      last few years has revealed that NF-kappaB is activated by carcinogens, tumor
      promoters, inflammatory cytokines, and by chemotherapeutic agents. The activation
      of NF-kappaB can suppress apoptosis, thus promoting chemoresistance and
      tumorigenesis. Interestingly, however, most chemopreventive agents appear to
      suppress the activation of the NF-kappaB through inhibition of NF-kappaB
      signaling pathway. These chemopreventive agents also sensitize the tumors to
      chemotherapeutic agents through abrogation of NF-kappaB activation. Overall,
      these observations suggest that NF-kappaB is an ideal target for chemoprevention
      and chemosensitization. This article reviews evidence supporting this hypothesis.

PMID- 12213583
TI  - Is HIF-1alpha a pro- or an anti-apoptotic protein?
AB  - Hypoxia-inducible factor-1 (HIF-1) is the major transcription factor specifically
      activated by hypoxia. It induces the expression of different genes whose products
      play an adaptive role for hypoxic cells and tissues. Besides these protective
      responses, HIF-1 and/or hypoxia have also been shown to be either anti-apoptotic
      or pro-apoptotic, according to the cell type and experimental conditions. More
      severe or prolonged hypoxia rather induces apoptosis that is, at least in part,
      initiated by the direct association of HIF-1alpha and p53 and p53-induced gene
      expression. On the other hand, HIF-1alpha dimerized with ARNT, as an active
      transcription factor, can protect cells from apoptosis induced by several
      conditions. This review is aimed to describe the different mechanisms that
      account for these opposite effects of HIF-1alpha.

PMID- 12213584
TI  - Is there a single mechanism for fatty acid regulation of gene transcription?
AB  - Besides their role as energetic molecules, fatty acids (FAs) also act as signals
      involved in regulating gene expression. This review focuses on a few examples of
      FA regulation. The hepatic lipogenic enzyme, fatty acid synthase (FAS) is
      negatively regulated by polyunsaturated FAs (PUFAs) which suppress sterol
      regulatory element-binding protein 1 (SREBP 1) gene expression and nuclear
      content in hepatocytes, thereby reducing FAS gene transcription. It was proposed
      recently that this reduction in SREBP 1 was the result of a PUFA-induced
      antagonism of ligand-dependent activation of the liver X nuclear receptor (LXR),
      known to be an inducer of the SREBP 1 gene. In contrast, several genes are turned
      on by long-chain (LCFAs) and nonmetabolized FAs in a physiologically relevant
      manner. These include the acyl-CoA oxidase (AOX), the liver carnitine
      palmitoyltransferase 1 (L-CPT 1) and the liver fatty acid binding protein (L
      FABP). While induction of AOX gene transcription appears to be PPARalpha
      dependent, that of the L-CPT 1 gene seems disconnected from PPAR activation.
      Results obtained in preadipocytes and in intestine cells are in support of a key
      role played by the beta/delta isoform of PPAR in LCFA induction of the FABP gene.
      Transcription of the phosphoenolpyruvate carboxykinase (PEPCK) gene is stimulated
      by unsaturated and nonmetabolized LCFAs specifically in adipocytes. Our results
      reported here support the notion that the mechanisms by which PPARgamma
      activators and FAs induce transcription of the PEPCK gene are distinct.
      Altogether these data argue that several FA effects are PPAR-independent.
      Evidences suggesting that other transcription factors might be involved are
      debated. It seems now clear that depending upon the cell-specific context and the
      target gene, FAs can take very different routes to alter transcription.

PMID- 12213585
TI  - Signaling cross-talk between hypoxia and glucose via hypoxia-inducible factor 1
      and glucose response elements.
AB  - The substrates oxygen and glucose are important for the appropriate regulation of
      metabolism, angiogenesis, tumorigenesis and embryonic development. The knowledge
      about an interaction between these two signals is limited. We demonstrated that
      the regulation of glucagon receptor, insulin receptor and L-type pyruvate kinase
      (L-PK) gene expression in liver is dependent upon a cross-talk between oxygen and
      glucose. The periportal to perivenous drop in O2 tension was proposed to be an
      endocrine key regulator for the zonated gene expression in liver. In primary rat
      hepatocyte cultures, the expression of the glucagon receptor and the L-PK mRNA
      was maximally induced by glucose under arterial pO2 whereas the insulin receptor
      was maximally induced under perivenous pO2. It was demonstrated for the L-PK gene
      that the modulation by O2 of the glucose-dependent induction occured at the
      glucose-responsive element (Glc(PK)RE) in the L-PK gene promoter. The reduction
      of the glucose-dependent induction of the L-PK gene expression under venous pO2
      appeared to be mediated via an interference between hypoxia-inducible factor 1
      (HIF-1) and the glucose-responsive transcription factors at the Glc(PK)RE. The
      glucose response element (GlcRE) also functioned as a hypoxia response element
      and, vice versa, a hypoxia-responsive element was functioning as a GlcRE. Thus,
      our findings implicate that the cross-talk between oxygen and glucose might have
      a fundamental role in the regulation of several physiological and
      pathophysiological processes.

PMID- 12213586
TI  - Genomic responses to herbal extracts: lessons from in vitro and in vivo studies
      with an extract of Ginkgo biloba.
AB  - Do herbal extracts offer effective dietary supplements to prevent deregulation of
      the transcriptome? Can they normalize deregulated transcriptomes of chronic human
      diseases? Are the effects of herbal extracts targeted to specific molecular
      pathways in tissue-specific manner? Are the effects of herbal supplements
      reversible? These questions pose important challenges to the fields of molecular
      nutrition and medicine, which are committed to understanding the molecular basis
      of physiology during health and disease. Transcription of the molecular
      information encoded in the deoxynucleotide sequences of DNA to the nucleotide
      sequences of RNA play a vital, causative, role in the coordinated adaptation of
      the organism to its changing environment and its nutritional needs. Pathogenesis
      is a manifestation of defects in transcription of the genome. Herbal extracts may
      target these obligatory processes. Increased availability of tools for
      quantitative and comprehensive analysis of messenger RNAs offer powerful means to
      understand and identify changes in these fundamental processes. Studies with the
      extract of Ginkgo biloba leaves show that the extract affects transcription of
      functionally diverse groups of genes in vitro and in vivo. The observations offer
      molecular evidence for bioactivity of the extract and offer an analytical
      strategy to define and predict physiological effects of complex mixtures of
      phytochemicals.

PMID- 12213587
TI  - Designed transcription factors as tools for therapeutics and functional genomics.
AB  - The paucity of tools that control expression of specific genes in vivo represents
      a major limitation of functional genomics in mammals; most available small
      molecule regulators of transcription-e.g. histone deacetylase inhibitors-exert
      pan-genomic effects. Recent developments in understanding the role of chromatin
      in regulating the genome, and of protein-DNA interactions have allowed the
      development of designed transcription factors that regulate specific genes in
      vivo (Reik et al., Curr Opin Genet Dev 2002;12:233). These proteins contain two
      modules: (i) a zinc finger protein (ZFP)-based DNA-binding domain (DBD) designed
      to recognize a specific sequence (for example, a motif in the promoter of a
      certain gene); (ii) a functional module (for example, a transcriptional
      activation or repression domain). Recent data describe the use of such designed
      transcription factors to regulate a variety of clinically relevant gene targets
      in human cells: these include MDR1, erythropoietin, erbB-2 and erbB-3, VEGF, and
      PPARgamma. In the case of VEGF (Liu et al., J Biol Chem 2001;276:11323),
      proportional upregulation by the designed transcription factor of all three
      distinct splice isoforms generated by this locus was observed, illuminating the
      utility of endogenous gene control in therapeutic settings (proper isoform ratio
      is essential for the proangiogenic function of VEGF). In the case of PPARgamma,
      use of a transcriptional repressor designed to downregulate the expression of two
      PPARgamma isoforms allowed "mutation-free reverse genetics" analysis that
      illuminated a unique role for the PPARgamma2 isoform in adipogenesis (Ren et al.,
      Genes Dev 2002;16:27). The ability to selectively activate or repress specific
      mammalian genes in vivo using designed transcription factors thus has
      considerable promise in clinical and in basic science settings.

PMID- 12213588
TI  - Diversity of acetylation targets and roles in transcriptional regulation: the
      human immunodeficiency virus type 1 promoter as a model system.
AB  - Persuasive evidence has accumulated that reversible acetylation of proteins is
      key post-translational modification regulating transcription in eukaryotes.
      Deacetylase inhibitors (such as trichostatin A) modulate the expression of
      approximately 2% of all cellular genes. We and others have demonstrated a marked
      transcriptional activation of the human immunodeficiency virus type 1 (HIV-1)
      promoter in response to deacetylase inhibitors. Deacetylation events seem to be
      an important mechanism of HIV-1 transcriptional repression during latency,
      whereas acetylation events play critical functional roles in HIV-1 reactivation
      from latency. These deacetylation/acetylation events are implicated in chromatin
      remodeling of the viral promoter region, as well as in modulating the functional
      properties of cellular and viral transcription factors binding to this promoter
      region. Thereby, the HIV-1 promoter constitutes a unique regulatory model system
      to study the complex relationship between acetylation processes and
      transcriptional activity.

PMID- 12213589
TI  - Oxidative stress, transcription factors and chromatin remodelling in lung
      inflammation.
AB  - Oxidative stress has been implicated in the pathogenesis of several inflammatory
      lung disorders. Oxidants and inflammatory mediators such as tumour necrosis
      factor-alpha (TNF-alpha) activate transcription factors such as nuclear factor
      kappaB (NF-kappaB) and activator protein-1 (AP-1) leading to the expression of
      pro-inflammatory genes. The expression of many genes, including those encoding
      pro-inflammatory mediators involves the remodelling of the chromatin structure
      provided by histone proteins. Histone acetylation causes the unwinding of
      chromatin structure therefore allowing transcription factor access to promoter
      sites. Nuclear histone acetylation is a reversible process, and is regulated by a
      group of acetyltransferases (HATs) which promote acetylation, and deacetylases
      (HDACs) which promote deacetylation. In addition, several co-activators,
      transcription factors and nuclear proteins also have histone acetyltransferase
      activity. Both TNF-alpha and the oxidant, hydrogen peroxide (H2O2) alter histone
      acetylation/deacetylation, and the activation of NF-kappaB and AP-1, leading to
      the release of the pro-inflammatory cytokine interleukin-8 (IL-8) in human
      alveolar epithelial cells (A549). Pharmacological inhibition of HDAC leads to the
      increased HAT activity, AP-1 and NF-kappaB activation, and IL-8 release by H2O2
      or TNF-alpha treatments. This suggests that the remodelling of chromatin by
      histone acetylation plays a role in the oxidant-mediated pro-inflammatory
      responses in the lungs.

PMID- 12213590
TI  - Transcriptional regulators of the human multidrug resistance 1 gene: recent
      views.
AB  - The multidrug resistance (MDR) phenotype is the major cause of failure of cancer
      chemotherapy. This phenotype is mainly due to the overexpression of the human
      MDR1 (hMDR1) gene. Several studies have shown that transcriptional regulation of
      this gene is unexpectedly complex and is far from being completely understood.
      Current work is aimed mainly at defining unclear and new control regions in the
      hMDR1 gene promoter as well as clarifying corresponding signaling pathways. Such
      studies provide new insights into the mechanisms by which xenobiotic molecules
      might modify the physiological hMDR1 expression as well as the possible role of
      oncogenes in the pathological dysregulation of the gene. Here we report recent
      findings on the regulation of hMDR1 which may help define specific targets aimed
      at modulating its transcription.

PMID- 12213591
TI  - Function of AP-1 target genes in mesenchymal-epithelial cross-talk in skin.
AB  - An increasing number of examples on the importance of mesenchymal-epithelial
      interactions in physiological (e.g. embryonic development) and pathological
      (tumourigenesis) processes have been described. This is best illustrated in the
      skin, where the well-controlled balance of keratinocyte proliferation and
      differentiation forms the basis for a proper histoarchitecture of the epidermis.
      Here, a double paracrine loop of cytokines, which are synthesised and secreted by
      cells of the epidermis (keratinocytes) and the underlying dermis (fibroblasts)
      seems to play a major role. The aim of this commentary is to review research that
      has investigated the role of specific subunits of transcription factor AP-1
      (Jun/Fos) in this regulatory network. Using an in vitro skin equivalent model
      strong evidence was provided for a critical and specific function of c-Jun and
      JunB in mesenchymal-epithelial interaction in the skin by regulating the
      expression of interleukin-1 (IL-1)-induced keratinocyte growth factor (KGF) and
      GM-CSF in fibroblasts. These factors, in turn, adjust the balance between
      proliferation and differentiation of keratinocytes ensuring proper architecture
      of the epidermis. This commentary will summarise our current knowledge on the
      molecular mechanisms underlying AP-1-dependent mesenchymal-epithelial
      interactions and discuss the physiological relevance of these in vitro findings
      in skin physiology and pathology.

PMID- 12213592
TI  - Evasion from proteasomal degradation by mutated Fos proteins expressed from FBJ
      MSV and FBR-MSV osteosarcomatogenic retroviruses.
AB  - c-Fos proto-oncoprotein is highly unstable, which is crucial for rapid gene
      expression shut-off and control of its intrinsic oncogenic potential. It is
      massively degraded by the proteasome in vivo in various situations. Although
      there is evidence that c-Fos can be ubiquitinylated in vitro, the unambiguous
      demonstration that ubiquitinylation is necessary for recognition and subsequent
      hydrolysis by the proteasome in vivo is still lacking. Moreover, genetic analysis
      have also indicated that c-Fos can be addressed to the proteasome via different
      mechanisms depending on the conditions studied. c-Fos has been transduced by two
      murine osteosarcomatogenic retroviruses under mutated forms which are more stable
      and more oncogenic. The stabilization is not simply accounted for by simple
      deletion of a C-terminal c-Fos destabilizer but, rather, by a complex balance
      between opposing destabilizing and stabilizing mutations. Though mutations in
      viral Fos proteins confer full resistance to proteasomal degradation,
      stabilization is limited because mutations also entail sensitivity to (an)
      unidentified proteolytic system(s). This observation is consistent with the idea
      that Fos-expressing viruses have evolved gene expression controls that avoid high
      protein accumulation-linked apoptosis.

PMID- 12213593
TI  - Regulation of the transcriptional activity of the nuclear factor-kappaB p65
      subunit.
AB  - Nuclear factor-kappaB (NF-kappaB) is well known for its role in inflammation,
      immune response, control of cell division and apoptosis. The function of NF
      kappaB is primarily regulated by IkappaB family members, which ensure cytoplasmic
      localisation of the transcription factor in the resting state. Upon stimulus
      induced IkappaB degradation, the NF-kappaB complexes move to the nucleus and
      activate NF-kappaB-dependent transcription. Over the years, a second regulatory
      mechanism, independent of IkappaB, has become generally accepted. Changes in NF
      kappaB transcriptional activity have been assigned to phosphorylation of the p65
      subunit by a large variety of kinases in response to different stimuli. Here, we
      give an overview of the kinases and signalling pathways mediating this process
      and comment on the players involved in tumour necrosis factor-induced regulation
      of NF-kappaB transcriptional activity. Additionally, we describe how other
      posttranslational modifications, such as acetylation and methylation of
      transcription factors or of the chromatin environment, may also affect NF-kappaB
      transcriptional activity.

PMID- 12213594
TI  - Reduction of tumor necrosis factor-alpha (TNF-alpha) related nuclear factor
      kappaB (NF-kappaB) translocation but not inhibitor kappa-B (Ikappa-B)-degradation
      by Rho protein inhibition in human endothelial cells.
AB  - Degradation of inhibitor kappa-B (Ikappa-B) followed by translocation of nuclear
      factor-kappaB (NF-kappaB) into the nucleus and activation of gene expression is
      essential in tumor necrosis factor-alpha (TNF-alpha)-signaling. In order to
      analyze the role of Rho proteins in TNF-alpha-induced NF-kappaB-activation in
      human umbilical cord vein endothelial cells (HUVEC) we used Clostridium difficile
      toxin B-10463 (TcdB-10463) which inactivates RhoA/Rac1/Cdc42 by glucosylation and
      Clostridium botulinum C3-toxin which inhibits RhoA/B/C by ADP-ribosylation.
      Exposure of HUVEC to 10 ng/mL TcdB-10463 or 2.5 microg/mL C3-toxin inhibited TNF
      alpha (100 ng/mL)-induced expression of a NF-kappaB-dependent reporter gene.
      Moreover, preincubation of HUVEC with 10 ng/mL TcdB-10463 reduced TNF-alpha
      related expression of interleukin-8 (IL-8), TNF-receptor associated factor-2
      (TRAF2), and human inhibitor of apoptosis protein 1 (hIAP1)-mRNA. Blocking of Rho
      reduced NF-kappaB DNA-binding as shown by electrophoretic mobility shift assays.
      TcdB-10463 and C3-toxin blocked TNF-alpha-related nuclear translocation of NF
      kappaB although Ikappa-Balpha/beta was still degraded. In contrast, TcdB-10463
      had no effect on IL-1beta-related NF-kappaB-translocation and activation in
      HUVEC. Neither 1 microM Rho kinase inhibitor Y-27632 nor microfilament
      depolymerization by 50 ng/mL C. botulinum C2-toxin blocked TNF-alpha-induced
      degradation of Ikappa-B, nuclear NF-kappaB translocation or expression of a NF
      kappaB-dependent reporter gene. Therefore, TNF-alpha-related Ikappa-B-degradation
      is Rho-independent in HUVEC, whereas a Rho protein-dependent signal is necessary
      to induce nuclear transport of NF-kappaB in these cells pointing to a novel and
      unique role of Rho in NF-kappaB-translocation.

PMID- 12213595
TI  - Differential activity by DNA-induced quarternary structures of POU transcription
      factors.
AB  - Recent structural studies on transcription factors from the POU family in complex
      with multiple cognate DNA enhancer elements have established a novel concept in
      DNA-mediated formation of distinct conformations of transcription regulator
      assemblies. Two crystal structures of the Oct-1 transcription factor in the
      presence of two different DNA sites have demonstrated how its POU DNA-binding
      segment is capable in forming two unrelated dimer arrangements, which is DNA
      motif dependent. While one arrangement allows binding of the Oct-1 specific
      coactivator OBF-1, binding of this coactivator is blocked in the second
      arrangement because the binding site is involved in its own dimer assembly.
      Conversely, two crystal structures of another POU transcription factor, Pit-1,
      have demonstrated how the same overall assembly is maintained in the presence of
      two different DNA response elements. However, since the distance of the two Pit-1
      half-binding sites on these elements differ by two base pairs, the overall
      dimensions of the two complexes vary, allowing binding of a specific represssor
      (N-CoR) in one conformation but not in the other. Thus, despite the occurrence of
      different DNA-mediated molecular mechanisms, the net result, conformation
      dependent binding of further regulators, is equivalent. These data introduce a
      concept where the DNA motif not only serves as binding site for specific
      transcription factors but also regulates their function by mediating specific
      transcription factor assemblies, which determine binding to conformation
      dependent coregulators.

PMID- 12213596
TI  - Multiple signaling pathways leading to the activation of interferon regulatory
      factor 3.
AB  - Virus infection of susceptible cells activates multiple signaling pathways that
      orchestrate the activation of genes, such as cytokines, involved in the antiviral
      and innate immune response. Among the kinases induced are the mitogen-activated
      protein (MAP) kinases, Jun-amino terminal kinases (JNK) and p38, the IkappaB
      kinase (IKK) and DNA-PK. In addition, virus infection also activates an
      uncharacterized VAK responsible for the C-terminal phosphorylation and subsequent
      activation of interferon regulatory factor 3 (IRF-3). Virus-mediated activation
      of IRF-3 through VAK is dependent on viral entry and transcription, since
      replication deficient virus failed to induce IRF-3 activity. The pathways leading
      to VAK activation are not well characterized, but IRF-3 appears to represent a
      novel cellular detection pathway that recognizes viral nucleocapsid (N)
      structure. Recently, the range of inducers responsible for IRF-3 activation has
      increased. In addition to virus infection, recognition of bacterial infection
      mediated through lipopolysaccharide by Toll-like receptor 4 has also been
      reported. Furthermore, MAP kinase kinase kinase (MAP KKK)-related pathways and
      DNA-PK induce N-terminal phosphorylation of IRF-3. This review summarizes recent
      observations in the identification of novel signaling pathways leading to IRF-3
      activation.

PMID- 12213597
TI  - Signal transduction to hypoxia-inducible factor 1.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that functions
      as a master regulator of O2 homeostasis. HIF-1 target genes encode proteins that
      increase O2 delivery and mediate adaptive responses to O2 deprivation. HIF-1
      activity is regulated by the cellular O2 concentration and by the major growth
      factor-stimulated signal transduction pathways. In human cancer cells, both
      intratumoral hypoxia and genetic alterations affecting signal transduction
      pathways lead to increased HIF-1 activity, which promotes angiogenesis, metabolic
      adaptation, and other critical aspects of tumor progression.

PMID- 12213598
TI  - Age-related decline in cellular response to oxidative stress: links to growth
      factor signaling pathways with common defects.
AB  - Accumulation of oxidative damage is believed to be a major contributor to the
      decline in physiologic function that characterizes mammalian aging, and recent
      studies suggest that how well you respond to acute oxidative stress is an
      important factor in determining longevity. Oxidant injury elicits a wide spectrum
      of responses ranging from proliferation to cell death. The particular outcome
      observed largely reflects the severity of the stress encountered and the relative
      degree of activation of various signal transduction pathways aimed at enhancing
      survival or inducing cell death. Herein we examine the relationship between
      pathways important in supporting cell survival in response to oxidant injury and
      those involved in regulating proliferation. We review evidence indicating that
      [Curr. Opin. Cell Biol. 10 (1998) 248] common pathways are indeed involved in
      regulating these responses, and [Physiol. Rev. 82 (2002) 47] alterations in
      shared signaling events likely account for the age-related decline in the ability
      of cells to respond to both proliferative signals and oxidant stimuli.

PMID- 12213599
TI  - Stress-induced premature senescence and tissue ageing.
AB  - Various human proliferative cell types exposed in vitro to many types of
      subcytotoxic stresses undergo stress-induced premature senescence (SIPS). The
      known mechanisms of appearance the main features of SIPS are reviewed: senescent
      like morphology, growth arrest, senescence-related changes in gene expression.
      All cell types undergoing SIPS in vivo, are likely to participate in the tissular
      changes observed along ageing. For instance, human diploid fibroblasts exposed in
      vivo and in vitro to pro-inflammatory cytokines display biomarkers of senescence
      and might participate in the degradation of the extracellular matrix observed in
      ageing.

PMID- 12213600
TI  - Stress-induced premature senescence and replicative senescence are different
      phenotypes, proteomic evidence.
AB  - In this paper, we illustrate how a proteomic analysis can be useful to approach
      complex biological problems, in this case the concept of stress-induced premature
      senescence (SIPS). According to the stochastic theories of ageing, damage that
      accumulate with time in the cellular components are responsible for cellular
      ageing. As a corollary, some sort of premature senescence should appear if the
      damage level is artificially increased due to the presence of stressing agents at
      subcytotoxic level. It has been shown, in several different models, that at a
      long-term after subcytotoxic stresses of many different natures, human diploid
      fibroblasts (HDFs) display biomarkers of replicative senescence (RS), which led
      to the concept of SIPS as compared to telomere-dependent RS. We compared RS and
      SIPS of HDFs by proteome analysis. SIPS was induced by two very different
      stressors: tert-butyhydroperoxide or ethanol. First, only a part of the protein
      expression changes observed in RS were also observed in SIPS. Second, HDFs in
      SIPS show changes specific either to the long-term effects of t-BHP or ethanol or
      independent of the nature of the stress. These changes have been termed
      "molecular scars" of subcytotoxic stresses. This work is also an excellent
      opportunity to discuss on important methodological issue in proteomics: the
      absolute requirement to start from reliable and reproducible models, which was
      the case in this study. We also focus on the data handling and statistical
      analysis allowing to use two-dimensional gel electrophoresis patterns in a semi
      quantitative analysis.

PMID- 12213601
TI  - Cellular glutathione and thiols metabolism.
AB  - Low molecular weight thiol-containing compounds have an essential role in many
      biochemical and pharmacological reactions due to the ease with each they are
      oxidized, and the rapidity with which they can be regenerated. Thioredoxin and
      glutathione (GSH) are two of the major small molecular weight thiol-containing
      compounds synthesized de novo in mammalian cells that participate in those
      functions. Understanding the mechanisms of thiol metabolism has special relevance
      to understanding the cell's defense against toxicant exposure and as the focal
      point in redox signaling. This commentary will, however, focus on GSH consumption
      and synthesis, and the role of thiols in signaling. The chemical reactions of
      GSH, including conjugation reactions mediated by glutathione S-transferases (GST)
      and oxidation reactions mediated by glutathione peroxidases will be described.
      The regulation of GSH synthesis will be illustrated from a compilation of studies
      designed to understand the various levels at which enzymatic GSH biosynthesis is
      controlled, and the signaling pathways that mediate them. The response of the
      cell to 4-hydroxynonenal (4HNE), a reactive aldehyde produced physiologically in
      response to inflammation and various air pollutants, will be explored in detail.
      Finally, the direct role of thiols as signaling molecules will be addressed, with
      particular attention given to "redox state." It is our aim that this commentary
      will lead the reader to appreciate that studies investigating the signaling for
      and regulation of thiol metabolism must never be generalized, and that
      perturbations in any of step of thiol metabolism may have etiological roles in
      genetically, virally, and environmentally borne pathologies.

PMID- 12213602
TI  - Glutathione catabolism as a signaling mechanism.
AB  - Glutathione (GSH) is the main intracellular thiol antioxidant, and as such
      participates in a number of cellular antitoxic and defensive functions.
      Nevertheless, non-antioxidant functions of GSH have also been described, e.g. in
      modulation of cell proliferation and immune response. Recent studies from our and
      other laboratories have provided evidence for a third functional aspect of GSH,
      i.e. the prooxidant roles played by molecular species originating during its
      catabolism by the membrane ectoenzyme gamma-glutamyl transpeptidase (GGT). The
      reduction of metal ions effected by GSH catabolites is capable to induce redox
      cycling processes leading to the production of reactive oxygen species
      (superoxide, hydrogen peroxide), as well as of other free radicals. Through the
      action of these reactive compounds, GSH catabolism can ultimately lead to
      oxidative modifications on a variety of molecular targets, involving oxidation
      and/or S-thiolation of protein thiol groups in the first place. Modulating
      effects of this kind have been observed on several important, redox-sensitive
      components of the signal transduction chains, such as cell surface receptors,
      protein phosphatase activities and transcription factors. Against this
      background, the prooxidant reactions induced by GSH catabolism appear to
      represent a novel, as yet unrecognized mechanism for modulation of cellular
      signal transduction.

PMID- 12213603
TI  - Glutathione, iron and Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disease involving
      neurodegeneration of dopaminergic neurons of the substantia nigra (SN), a part of
      the midbrain. Oxidative stress has been implicated to play a major role in the
      neuronal cell death associated with PD. Importantly, there is a drastic depletion
      in cytoplasmic levels of the thiol tripeptide glutathione within the SN of PD
      patients. Glutathione (GSH) exhibits several functions in the brain chiefly
      acting as an antioxidant and a redox regulator. GSH depletion has been shown to
      affect mitochondrial function probably via selective inhibition of mitochondrial
      complex I activity. An important biochemical feature of neurodegeneration during
      PD is the presence of abnormal protein aggregates present as intracytoplasmic
      inclusions called Lewy bodies. Oxidative damage via GSH depletion might also
      accelerate the build-up of defective proteins leading to cell death of SN
      dopaminergic neurons by impairing the ubiquitin-proteasome pathway of protein
      degradation. Replenishment of normal glutathione levels within the brain may hold
      an important key to therapeutics for PD. Several reports have suggested that iron
      accumulation in the SN patients might also contribute to oxidative stress during
      PD.

PMID- 12213604
TI  - Glutathionylation of proteins by glutathione disulfide S-oxide.
AB  - Aqueous solution of S-nitrosoglutathione (GSNO) underwent spontaneous chemical
      transformation that generated several glutathione derivatives including
      glutathione sulfonic acid (GSO3H), glutathione disulfide S-oxide (GS(O)SG),
      glutathione disulfide S-dioxide, and glutathione disulfide. Surprisingly, GS(O)SG
      (also called glutathione thiosulfinate), which was not identified as a metabolite
      of GSNO previously, was one of the major products derived from GSNO. This
      compound was very reactive toward any thiol and the reaction product was a mixed
      disulfide. The rate of reaction of GS(O)SG with 5-mercapto-2-nitro-benzoate was
      nearly 20-fold faster than that of GSNO. The mechanism for the formation of
      GS(O)SG was believed to involve the sulfenic acid (GSOH) and thiosulfinamide
      (GS(O)NH2) intermediates; the former underwent self-condensation and the latter
      reacted with GSH to form GS(O)SG. Many reactive oxygen and nitrogen species were
      also capable of oxidizing GSH or GSSG to form GS(O)SG, which likely played a
      central role in integrating both the oxidative and nitrosative cellular responses
      through thionylation of thiols. Treatments of rat brain tissue slices with
      oxidants resulted in an enhanced thionylation of proteins with a concomitant
      increase in cellular level of GS(O)SG, suggesting that this compound might play a
      second messenger role for stimuli that produced a variety of oxidative species.

PMID- 12213605
TI  - Cell signalling and the glutathione redox system.
AB  - The reduction/oxidation (redox) state of the cell is a consequence of the balance
      between the levels of oxidising and reducing equivalents. A reducing
      intracellular environment is often associated with cell survival; however, redox
      unbalance is necessary since it represents a regulatory sensor for several
      nuclear transcription factors. Activator protein 1 (AP-1), nuclear factor-kappaB
      (NF-kappaB) and protein tyrosine phosphatases 1-B (PTP-1B) are some of the well
      known molecular factors for which a redox modulation of their activity has been
      demonstrated. The glutathione buffer system modulates cell response to redox
      changes induced by either external or intracellular stimuli. This paper
      summarises recent knowledge on the role played by several redox modulators in
      inducing signalling events that finally regulate cell cycle progression.

PMID- 12213606
TI  - Thioredoxins and related proteins in photosynthetic organisms: molecular basis
      for thiol dependent regulation.
AB  - Thioredoxins are small molecular weight disulfide oxidoreductases specialized in
      the reduction of disulfide bonds on other proteins. Generally, the enzymes which
      are selectively and reversibly reduced by these proteins oscillate between an
      oxidized and inactive conformation and a reduced and active conformation.
      Thioredoxin constitutes the archetype of a family of protein disulfide
      oxidoreductases which comprises glutaredoxin and protein disulfide isomerase.
      Thioredoxin and glutaredoxin serve many roles in the cell, including the redox
      regulation of target enzymes and transcription factors. They can also serve as
      hydrogen donors to peroxiredoxins, recently discovered heme free peroxidases, the
      function of which is to get rid of hydroperoxides in the cell. This review
      describes the molecular basis for the functioning and interaction between these
      enzymes in photosynthetic organisms.

PMID- 12213607
TI  - Neurologic manifestations of iron deficiency in childhood.
AB  - Iron deficiency is a common disorder in pediatric patients. Although the most
      common manifestation is that of anemia, iron deficiency is frequently the source
      of a host of neurologic disorders presenting to general pediatric neurologic
      practices. These disorders include developmental delay, stroke, breath-holding
      episodes, pseudotumor cerebri, and cranial nerve palsies. Although frequent, the
      identification of iron deficiency as part of the differential diagnosis in these
      disorders is uncommon and frequently goes untreated. The purpose of the current
      review is to highlight what is understood regarding iron deficiency and it's
      underlying pathophysiology as it relates to the brain, and the association of
      iron deficiency with common neurologic pediatric disease.

PMID- 12213608
TI  - Prognostic value of neonatal discontinuous EEG.
AB  - The burst suppression pattern on the neonatal electroencephalogram (EEG) is
      associated with a poor outcome. However, this serious abnormality constitutes
      only a small proportion of discontinuous neonatal EEGs. We sought to establish
      whether any easily measurable parameters among the broad range of excessively
      discontinuous neonatal EEGs are predictive of outcome. We retrospectively
      reviewed the EEGs and medical records of 43 term infants with excessively
      discontinuous EEGs. We quantitated 10 parameters in the bursts and interburst
      intervals, among them the predominant interburst interval duration (defined as
      the duration of more than 50% of all interburst intervals of an EEG). Univariate
      and multivariate analyses were performed on the 10 EEG variables in relation to
      neurologic outcome and subsequent epilepsy. Based on multivariate analysis, a
      single easily measurable EEG parameter related significantly to outcome. A
      predominant interburst interval duration of more than 30 seconds correlated with
      the occurrence of both unfavorable neurologic outcome and subsequent epilepsy (P
      = 0.040 and P = 0.033, respectively). In conclusion, a infant whose EEG contains
      a predominant interburst interval duration of more than 30 seconds has a 100%
      probability of experiencing severe neurologic disabilities or death and an 86%
      chance of developing subsequent epilepsy. This easily quantitated EEG parameter
      could be valuable for the early estimation of neurologic prognosis.

PMID- 12213609
TI  - Neurotrophin-4 and glial cell line-derived neurotrophic factor in cerebrospinal
      fluid from meningitis/encephalitis patients.
AB  - The neurotrophin-4 and glial cell line-derived neurotrophic factor levels were
      measured in cerebrospinal fluid from 61 patients with bacterial meningitis, viral
      meningitis, or encephalitis, and other diseases by means of two-site enzyme
      linked immunoassay. Elevated cerebrospinal fluid levels of neurotrophin-4 were
      demonstrated in four of the 11 patients with bacterial meningitis, and seven of
      the 23 patients with viral meningitis or encephalitis. None of the other patients
      demonstrated elevation of the neurotrophin-4 level in cerebrospinal fluid. The
      neurotrophin-4 levels in cerebrospinal fluid were correlated with the numbers of
      total and mononuclear cells in patients with viral meningitis/encephalitis. In
      patients with bacterial meningitis, three of the four patients with elevated
      neurotrophin-4 levels exhibited persistent abnormalities on computed tomography,
      and one revealed transient subdural effusion. On the other hand, none of the
      seven patients without neurotrophin-4 elevation had persistent computed
      tomography abnormalities, and five patients demonstrated transient computed
      tomography abnormalities. The glial cell line-derived neurotrophic factor levels
      were below the detection limit, or only slightly higher than the detection limit,
      in the patients with or without central nervous system infections. Although the
      precise roles of neurotrophin-4 and glial cell line-derived neurotrophic factor
      in central nervous system infections remain to be determined, neurotrophin-4
      might play a neuroprotective or immunomodulatory role in central nervous system
      infections.

PMID- 12213610
TI  - Attitudes of medical students toward pediatric neurology.
AB  - Planning strategies to encourage students to pursue a career in pediatric
      neurology requires assessment of their attitudes and career choices. A structured
      30-item questionnaire was designed to examine students' attitudes toward
      pediatric neurology. In the study, 161 final-year medical students (1999-2000),
      20-26 years of age (mean, 23 years of age) were included prospectively. Although
      most students had been taught by a pediatric neurologist and considered
      neurologic disorders interesting, 77%-100% had unfavorable attitudes. Although
      79% considered pediatric neurology as a future career option, only nine students
      (6%) selected it as their first choice. Our findings highlight some aspects that
      might be targeted to promote students' interest in pediatric neurology and
      improve their learning experiences.

PMID- 12213611
TI  - Neurodevelopmental outcome in children with fetal hydrocephalus.
AB  - Thirty-eight children with fetal hydrocephalus treated surgically during the
      neonatal period were analyzed concerning their neurodevelopmental outcome by
      means of a follow-up study. The mean gestation at diagnosis was 31.1 weeks, and
      the mean postconceptual age at the first operation was 36.3 weeks. The ages of
      the patients at the last follow-up ranged from 3.8 to 11.8 years (mean = 7.4
      years of age). During the follow-up period, they underwent neurologic
      examinations and were also evaluated to determine the developmental quotient or
      intelligence quotient. The relationships between age at diagnosis or the first
      operation for hydrocephalus and neurodevelopmental outcome, and between the
      lateral ventricular width/hemispheral width ratio at diagnosis and age at
      diagnosis or the first operation, and neurodevelopmental outcome were
      statistically evaluated. The neurodevelopmental outcome in the patients was
      normal in three patients, borderline intelligence in one patient, mental
      retardation in seven patients, and motor disturbance in 27 patients (five of whom
      were intellectually normal). The etiology was a major determinant of the outcome
      in the children with early postnatal surgical treatment of fetal hydrocephalus.
      Furthermore, an early onset and a high lateral ventricular width/hemispheral
      width ratio at diagnosis of hydrocephalus were significantly correlated with a
      poor intellectual outcome.

PMID- 12213612
TI  - Brain glucose metabolism in Rett Syndrome.
AB  - Rett syndrome is a progressive neurologic disorder affecting girls in early
      childhood with loss of achieved psychomotor abilities and mental retardation. Six
      sedated female patients (4 to 15 years of age) with a diagnosis of Rett syndrome
      were studied with [(18)F]fluorodeoxyglucose (FDG) and underwent positron emission
      tomography scanning of the brain. Relative tracer concentrations between
      different areas of the brain were assessed, and results were compared with 18 age
      matched control subjects. Patients were divided into two age groups: 3 to 8 years
      of age and 9 to 15 years of age. A relative decrease in [(18)F]FDG uptake in the
      lateral occipital areas in relation with the whole brain and a relative increase
      in the cerebellum was evident in both age groups (P < 0.001, unpaired Student t
      test). A relative increase in frontal tracer uptake was observed in the younger
      group. Sensorimotor areas and relations between cortical and subcortical
      structures were preserved in all patients. Changes in glucose cerebral metabolism
      resemble the regional distribution of normal children less than 1 year of age,
      likely reflecting a maturational arrest. Changes in frontal areas parallel those
      in postmortem N-methyl-D-aspartate receptor densities and could correlate with
      different clinical stages of the disease. This pattern differs from those
      described in Down syndrome, autism, and Alzheimer's disease.

PMID- 12213613
TI  - Unidentified bright objects associated with features of neurofibromatosis 1.
AB  - Unidentified bright objects are commonly observed on magnetic resonance imaging
      in young neurofibromatosis 1 patients, but their clinical and pathologic
      significance is largely unknown. Diagnostic features of neurofibromatosis 1
      include cafe-au-lait spots, intertriginous freckling, Lisch nodules,
      neurofibromas, bony lesions, and optic glioma. We investigated the relationship
      between unidentified bright objects and other features of neurofibromatosis 1.
      Data from the National Neurofibromatosis Foundation International Database
      included 523 neurofibromatosis 1 patients between 2 and 20 years of age who had
      cranial magnetic resonance imaging examinations. The presence or absence of
      unidentified bright objects, diagnostic features of neurofibromatosis 1, and
      central nervous system neoplasms was known in these patients. Logistic regressive
      models were used to measure associations between unidentified bright objects and
      the other features while controlling for age. The occurrence of unidentified
      bright objects was associated with the number of diagnostic features, but most
      significantly with central nervous system neoplasms other than optic gliomas
      [odds ratio (OR) = 9.0, 95% confidence interval (CI) = 1.2-70], optic gliomas (OR
      = 2.1, 95% CI = 1.2-3.6), subcutaneous neurofibromas (OR = 2.0, 95% CI = 1.3
      3.1), and Lisch nodules (OR = 1.6, 95% CI = 1.1-2.3). These findings suggest a
      common causal mechanism between unidentified bright objects and these cardinal
      clinical features in children with neurofibromatosis 1.

PMID- 12213614
TI  - Benign course of central pontine myelinolysis in a patient with anorexia nervosa.
AB  - Central pontine myelinolysis is a rare neurologic disorder defined by symmetric
      demyelination of the central base of the pons. Until recently its outcome was
      considered invariably poor if not fatal. We report a 15-year-old female patient
      with severe anorexia nervosa who acutely developed a locked-in syndrome. Magnetic
      resonance imaging revealed a central pontine lesion. There was no serum sodium
      abnormality. The corticospinal and corticonuclear tracts were intact, as assessed
      by serial neurophysiologic studies. Finally, the patient recovered completely
      both clinically and radiologically. This article discusses these observations in
      the light of recent reports on similar benign outcomes of central pontine
      myelinolysis. Although electrolyte imbalances could be overestimated and the
      clinical significance of the radiologic lesion is uncertain, the functional
      assessment of the corticospinal and corticonuclear fibers might have prognostic
      value.

PMID- 12213615
TI  - A novel mutation of late-onset very-long-chain acyl-CoA dehydrogenase deficiency.
AB  - We describe a novel mutation in three patients with the myopathic form of very
      long-chain acyl-CoA dehydrogenase deficiency. Three siblings born to second
      degree cousins of Jewish-Iraqi origin exhibited rhabdomyolysis and myoglobinuria
      as the presenting signs of the mild late-onset form of very-long-chain acyl-CoA
      dehydrogenase deficiency. We screened the patients for mutations in the very-long
      chain acyl-CoA dehydrogenase gene by amplification of all 20 exons and analysis
      by single-stranded conformation variance on gel electrophoresis. The patients
      were homozygous for a novel mutation G637A that alters alanine 173 to threonine.
      We hypothesize that this missense substitution caused a mild change of enzyme
      function correlating with the mild clinical features and, thus, favoring a
      genotype-phenotype correlation.

PMID- 12213616
TI  - Childhood-onset cluster headache.
AB  - Cluster headache, the most painful of the primary headaches, is a disorder with
      well-known diagnostic criteria. The condition usually begins in the second decade
      of life; the prevalence of childhood onset is approximately 0.1%. A 7-year-old
      female who suffered daily from severe strictly unilateral right orbital attacks
      lasting approximately 30 minutes associated with autonomic symptoms is reported
      herein. They were primarily misdiagnosed as psychogenic headaches. There was no
      family history for migraine or cluster headaches; physical and neurologic
      examinations and magnetic resonance imaging did not suggest any association with
      head trauma or vascular disorders. After a negative indomethacin test, daily
      intravenous administration of prednisolone terminated the attacks on the third
      day of the treatment. According to the classification and diagnostic criteria for
      headache disorders of the International Headache Society the child fulfilled the
      criteria for episodic cluster headaches. The pathogenesis, clinical
      manifestation, autonomic features, genetics, and family history of cluster
      headaches during childhood are reviewed in this report. Prophylactic medication
      and symptomatic treatment options are discussed, especially concerning the
      rationale of use of steroids in children with cluster headaches.

PMID- 12213617
TI  - L-2-hydroxyglutaric aciduria in two siblings.
AB  - Two Pakistani siblings with L-2-hydroxyglutaric aciduria are reported herein. A 6
      year-old male and a 2-year-old female, born to consanguineous parents, had
      chronic slowly progressive neurodegenerative disorder with insidious onset after
      infancy. Mental regression and seizures were evident in both patients, whereas
      cerebellar dysfunction was the main motor handicap in the male and pyramidal
      symptoms were prominent in the female. Magnetic resonance imaging revealed
      bilateral symmetrical abnormal signal in the subcortical white matter, internal
      and external capsules, basal ganglia, and dentate nuclei. The underlying
      metabolic defect, which is likely inherited in an autosomal recessive mode,
      remains unknown in this disorder.

PMID- 12213618
TI  - L-alanine supplementation in late infantile glycogen storage disease type II.
AB  - We report a male with late infantile glycogen storage disease type II (Pompe's
      disease) who presented at 12 months of age with muscular hypotonia and
      developmental delay. Oral supplementation with L-alanine has been administered
      for 5 years. Progression of skeletal myopathy was slow, and cardiomyopathy
      resolved almost completely. L-alanine may be a valuable supplement for infants
      with glycogen storage disease type II.

PMID- 12213619
TI  - Traumatic posterior cerebral artery occlusion in a 14-month-old child.
AB  - Following a head injury, a 14-month-old male presented with neck stiffness and 24
      hours later developed bilateral lateral rectus palsies. An unenhanced cerebral
      computed tomographic scan performed on admission revealed evidence of
      subarachnoid hemorrhage, cerebral edema, and mild-to-moderate compensated
      supratentorial hydrocephalus. A second scan performed 96 hours after the head
      injury revealed a mural thrombus at the tip of the basilar artery without any
      evidence of infarction. A third scan performed 12 days later revealed that the
      thrombus had resolved. However, a left posterior cerebral artery territory
      infarct was visualized. We postulate that the thrombus had embolized to the left
      posterior cerebral artery and caused occlusion of its cortical branch and
      subsequent infarction. A magnetic resonance angiography performed 20 days later
      excluded any vascular abnormality. The bilateral lateral rectus palsies persisted
      at the 6-month follow-up. To our knowledge, a head injury leading to a posterior
      cerebral artery territory infarct has not been reported earlier in a young child.

PMID- 12213620
TI  - Antioxidant properties of cabergoline: inhibition of brain auto-oxidation and
      superoxide anion production of microglial cells in rats.
AB  - We evaluated the effect of cabergoline on superoxide anion production by rat
      microglial cells using a 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1, 2
      a]pyrazin-3-one-dependent chemiluminescence assay. Cabergoline dose-dependently
      inhibited superoxide anion production by microglial cells stimulated with phorbol
      myristate acetate or opsonized zymosan, while it had no superoxide dismutase-like
      activity. We also studied the effects of cabergoline and alpha-tocopherol on
      thiobarbituric acid reactive substances formation in homogenized brain-tissue in
      rats. Cabergoline was stronger than alpha-tocopherol in inhibiting auto
      oxidation. While cabergoline is commonly used to treat the motor dysfunction of
      Parkinson's disease, it may also be effective in inhibiting oxidative stress, a
      possible mechanism of dopaminergic neuronal degeneration in Parkinson's disease.

PMID- 12213621
TI  - Behavioral improvement and dopamine release in a Parkinsonian rat model.
AB  - Glial cell-line derived neurotrophic factor (GDNF) gene therapy might offer new
      strategies for the treatment of Parkinson's disease (PD). GDNF is a potent
      dopaminergic (DA) neurotrophic factor. The effect of GDNF gene therapy was
      assessed using anatomical, behavioral, and neurochemical approaches. We examined
      the protective effect of increased striatal GDNF levels achieved by delivery of
      an adenoviral vector (Ad-) encoding human GDNF (Ad-GDNF). Animals were injected
      with Ad-GDNF prior to striatal lesion. Striatal DA concentration was measured by
      microdialysis. Animals receiving 6-hydroxydopamine (6-OHDA) only showed a
      significant decrease in rotation when compared to those receiving Ad-GDNF prior
      to the 6-OHDA neurotoxin. Under basal conditions, the Ad-GDNF group showed a
      significant (P < or = 0.05) increase (1880%) in DA concentration when compared to
      the 6-OHDA group. Amphetamine challenge induced a significantly (P < or = 0.05)
      higher release of DA in the Ad-GDNF group than in the 6-OHDA group. These
      findings show that long-term delivery of GDNF protein in the striatum provides
      significant cell, behavioral, and neurochemical protection.

PMID- 12213622
TI  - Modulation of adenylyl cyclase activity by baclofen in the developing rat brain:
      difference between cortex, thalamus and hippocampus.
AB  - Ontogenetic changes in the levels of GABA(B) receptors and their ability to
      modulate adenylyl cyclase (AC) activity were analyzed in rat cortex, thalamus and
      hippocampus. The relative numbers of GABA(B) receptors (measured as saturable,
      high-affinity [(3)H](-)baclofen binding sites) in cortex and thalamus were high
      already at postnatal day 1 (PD 1) and they reached a maximum at PD 25 and PD 12,
      respectively. There were no detectable high-affinity [(3)H](-)baclofen binding
      sites in hippocampus between birth and PD 12 and low-affinity [(3)H](-)baclofen
      binding attained at PD 12 did not change in adulthood (PD 90). Whereas GTP
      stimulated AC activity in cortex and thalamus was depressed by baclofen, it was
      enhanced in hippocampus. These data indicate that the inhibitory effect of
      baclofen on AC in cortex and thalamus is primarily mediated through the alpha
      subunits of G(i)/G(o) proteins. The stimulatory effect of baclofen in hippocampus
      may be explained by engagement of Gbetagamma subunits.

PMID- 12213623
TI  - The supratrigeminal region of the rat sends GABA/glycine-cocontaining axon
      terminals to the motor trigeminal nucleus on the contralateral side.
AB  - The supratrigeminal region (STR), a reticular zone capping the motor trigeminal
      nucleus (Tm), contains gamma-aminobutyric acid (GABA)ergic and glycinergic
      neurons which send axons to the contralateral Tm (J. Comp. Neurol. 373 (1996)
      498). In the present study we observed that some single synaptic terminals upon
      Tm motoneurons showed immunoreactivities (IRs) for both glutamic acid
      decarboxylase (GAD) and glycine transporter 2 (GlyT2). After injecting
      biotinylated dextran amine (BDA) into the STR, we further observed in the Tm
      contralateral to the BDA injection that some BDA-labeled axon terminals in close
      contact with Tm motoneurons showed both GAD- and GlyT2-IRs. Thus, the STR was
      indicated to send GABAergic/glycinergic axon terminals contralaterally to Tm
      motoneurons.

PMID- 12213624
TI  - Mutations in the rat myelin basic protein gene are associated with specific
      alterations in other myelin gene expression.
AB  - The Long Evans shaker (les) rat is a myelin basic protein (MBP) mutant that
      exhibits severe central nervous system (CNS) dysmyelination. We used a
      combination of immunohistochemistry, immunoblot and Northern blot analyses to
      determine the effect of MBP deficits on the expression of other CNS myelin genes
      in this mutant. Immunohistochemistry revealed a marked reduction in all major
      myelin proteins and differences in their intracellular distribution. Immunoblots
      confirmed the decreased expression of these proteins and indicated that relative
      levels of proteolipid protein (PLP) and DM20 were altered in this mutant.
      Quantitation of mRNA levels indicated that decreases in PLP and DM20 were a
      result of changes in mRNA levels but detected no change in other myelin gene
      transcripts.

PMID- 12213625
TI  - Effects of Ba-Wei-Die-Huang-Wan on the cholinergic function and protein
      expression of M2 muscarinic receptor of the urinary bladder in diabetic rats.
AB  - The study investigated the effect of a traditional Chinese herbal preparation 'Ba
      Wei-Die-Huang-Wan' on the cholinergic function of the urinary bladder in diabetic
      rats, as well as its influence on the protein expression of muscarinic M(2)
      receptors. Wistar rats were divided into three groups: (1) control rats; (2) 2
      week streptozotocin-induced diabetic rats; and (3) diabetic rats treated with Ba
      Wei-Die-Huang-Wan 26 mg/kg thrice daily for 3 days. A dose-response study was
      performed for bladder muscle strip contractile response to a muscarinic agonist,
      arecaidine propargyl ester (APE). The amount of M(2) receptor protein in the
      bladder was measured by Western immunoblotting using monoclonal antibodies. The
      bladder contractile response to APE was significantly increased in the diabetic
      rats compared to the control. The M(2) receptor protein density was also
      significantly higher by 106% (P < 0.01, n = 8) in diabetes. Ba-Wei-Die-Huang-Wan
      treatment significantly lowered the plasma glucose level of the diabetic rats.
      The increases in contractile response to APE as well as the M(2) receptor protein
      density were partially reversed by the treatment. In conclusion, there was an
      over-expression of M(2) receptor resulting in hyper-contractility in the bladder
      of diabetic rats. Ba-Wei-Die-Huang-Wan significantly alleviated the alterations.

PMID- 12213626
TI  - Sex differences in the citrus lemon essential oil-induced increase of hippocampal
      acetylcholine release in rats exposed to a persistent painful stimulation.
AB  - The microdialysis technique was used to study the ability of essential oil from
      citrus lemon to modulate hippocampal acetylcholine (ACh) release in male and
      female rats. Animals were allowed to inhale this odor while experiencing a
      persistent nociceptive input (50 microl formalin, 5%) or under control conditions
      (sham-injection). In males, exposure to the essential oil did not change the time
      course and magnitude of the ACh increase induced by pain. In females, the pain
      induced increase of ACh was delayed and increased by exposure to lemon essential
      oil. The present results indicate that lemon essential oil affects the ACh
      release differently in male and female rats during a painful condition.

PMID- 12213627
TI  - Differential coupling of N- and P/Q-type calcium channels to glutamate exocytosis
      in the rat cerebral cortex.
AB  - In nerve terminals, the activation of Ca(2+) channels of either the P/Q or N type
      triggers glutamate release. In turn, presynaptic metabotropic glutamate receptors
      control this process through the modulation of these Ca(2+) channels. By
      measuring glutamate release from cerebrocortical nerve terminals we show that at
      physiological concentrations of extracellular Ca(2+), the agonist L(+)-2-amino-4
      phosphonobutyrate only reduced the N-type channel coupled release. However, at
      lower concentrations of extracellular calcium the contribution of N-type channels
      was abolished and P/Q-type channels were entirely responsible for the remaining
      release of glutamate. Under these conditions, L(+)-2-amino-4-phosphonobutyrate
      was capable of reducing the P/Q-type channel mediated release. These results
      indicate that N-type Ca(2+) channels are less efficiently coupled to glutamate
      release than P/Q-type channels and that this differential coupling may have
      important implications for presynaptic modulation of synaptic transmission.

PMID- 12213628
TI  - Increased inhibition by agouti-related peptide of ventromedial hypothalamic
      neurons in rats overweight due to early postnatal overfeeding.
AB  - Melanocortins, e.g. alpha-melanocyte stimulating hormone, are involved in the
      central nervous regulation of body weight. Agouti-related peptide (AGRP) as an
      endogenous melanocortin receptor antagonist induces feeding. Overexpression leads
      to obesity. Rats that grow up in small litters develop persistent hyperphagia and
      are overweight throughout life. Changes in the neuronal activity of the
      ventromedial hypothalamic nucleus (VMH) that signals satiety with activation
      might be involved. We studied single unit activity in hypothalamic brain slices.
      Melanocortins activated or inhibited similarly in control and small litter rats.
      AGRP mainly inhibited VMH neurons of overweight rats (t-test, P < 0.005, n = 33),
      whereas it also activated neurons of controls. This increased inhibition of VMH
      neurons by AGRP in early postnatally overnourished rats might contribute to the
      changed regulation leading to a persistent overweight condition throughout life.

PMID- 12213629
TI  - A water-soluble synthetic spicamycin derivative (San-Gly) decreases mechanical
      allodynia in a rodent model of neuropathic pain.
AB  - The goal of this study was to examine the effects of synthetic spicamycin
      derivative, SAN-Gly, on mechanical allodynia in a spared nerve injury animal
      model of neuropathic pain. Adult male rats underwent surgical ligation and
      cutting of the common peroneal and tibial nerves, which produced a mechanical
      allodynia within 2-4 days. One week after the surgery, SAN-Gly was administered
      via intravenous injection. Mechanical allodynia was measured using von-Frey
      hairs. Spicamycin produced a significant reduction in mechanical allodynia for up
      to 6 weeks. This study demonstrates that SAN-Gly may be of potential use in
      treating patients with neuropathic pain.

PMID- 12213630
TI  - Transient up-regulation of elongation factor-2 kinase (Ca2+/calmodulin-dependent
      protein kinase III) messenger RNA in developing mouse brain.
AB  - Elongation factor-2 kinase (eEF-2K) is a Ca(2+)/calmodulin-dependent protein
      kinase that is highly specific for eukaryotic elongation factor-2. In the present
      study, we examined the developmental expression of eEF-2K messenger RNA (mRNA) in
      the mouse brain. At E13, the expression of eEF-2K mRNA is already evident in both
      ventricular and mantle zones throughout the neuroaxis with a rostrocaudal
      increasing gradient. During late embryonic and early postnatal stages, eEF-2K
      mRNA is transiently up-regulated in the cerebral cortex and hippocampal pyramidal
      cell layer. After birth, the expression of eEF-2K mRNA gradually decreased
      throughout the brain. In the mature brain, eEF-2K mRNA is expressed moderately
      only in the cerebellar and dentate granule cell layers, and weakly in the
      cerebral cortex, hippocampal pyramidal cell layer and olfactory bulb. These
      findings suggest that eEF-2K may be involved in early neuronal events such as
      proliferation, differentiation, and establishment of synaptic connections.

PMID- 12213631
TI  - Loss of medial septal modulation of dentate gyrus physiology in young mice
      overexpressing human beta-amyloid precursor protein.
AB  - Mice overexpressing the human mutant beta-amyloid precursor protein (hbetaAPP;
      PDAPP mice) show deficits in hippocampal-dependent spatial learning and
      hippocampal short- and long-term plasticity at ages preceding Abeta plaque
      deposition. We determined whether young PDAPP mice also exhibit alterations in
      septohippocampal function in vivo, which plays an important role in cognitive
      function. Electrical stimulation of the medial septum significantly increased
      neuronal excitability and reduced paired-pulse facilitation in the dentate gyrus.
      Medial septal-induced facilitation of dentate neuronal excitability was reduced
      in PDAPP mice. The inhibitory effects of medial septum stimulation on dentate
      paired-pulse facilitation were also attenuated in PDAPP mice. Young mice
      overexpressing hbetaAPP exhibit early abnormalities in neural circuits implicated
      in cognitive function that may play an important role in the more profound
      deficits observed in aged PDAPP mice.

PMID- 12213632
TI  - 1-Methyl-4-phenylpyridinium and 3-nitropropionic acid diminish cortical synthesis
      of kynurenic acid via interference with kynurenine aminotransferases in rats.
AB  - The aim of the present study was to evaluate the effect of mitochondrial
      inhibitors, 1-methyl-4-phenylpyridinium (MPP(+)) and 3-nitropropionic acid (3
      NPA), on the brain production of endogenous glutamate antagonist, kynurenic acid
      (KYNA). MPP(+) and 3-NPA dose-dependently impaired the synthesis of KYNA in rat
      cortical slices. Enzymatic studies revealed that MPP(+) inhibits in a
      concentration-dependent manner the activity of kynurenine aminotransferase II
      (KAT II), but not the activity of kynurenine aminotransferase I (KAT I). 3-NPA
      impaired the activity of both enzymes, KAT I and KAT II. Thus, MPP(+)- and 3-NPA
      evoked neurotoxicity may be at least partially associated with the depletion of
      KYNA.

PMID- 12213633
TI  - Angiotensin II influences the hyperpolarization-activated current Ih in neurones
      of the rat paraventricular nucleus.
AB  - The hypothalamic paraventricular nucleus (PVN) consists of mainly two types of
      neurones (type I and type II), according to their characteristic
      electrophysiological properties. An excitatory influence of angiotensin II (Ang
      II) on PVN neurones has been shown to be mediated by the AT(1) receptor. We
      investigated the underlying mechanism of the Ang II effect on PVN neurones with
      patch-clamp experiments. Using current-clamp mode, we identified a sag in 59% of
      only type II neurones due to a hyperpolarization-activated current I(h). Voltage
      clamp measurements revealed that Ang II (1 microM) provokes a shift of the I(h)
      activation curve to more depolarized values by 8.1 mV, an effect reduced by the
      additional application of the AT(1) receptor antagonist Losartan (10 microM).
      These findings suggest that the excitatory effect of Ang II in type II neurones
      is at least partially due to an increased population of active I(h) channels.

PMID- 12213634
TI  - Cyclooxygenase-1 gene knockout does not alter middle cerebral artery occlusion in
      a mouse stroke model.
AB  - Cyclooxygenase (COX) is crucial in inflammation; COX-1 is constitutional, and COX
      2 is inducible. In this study, neurological function and infarct volume were
      evaluated at 24 h after permanent endovascular middle cerebral artery occlusion
      (MCAO) in both COX-1-gene knockout (homozygous or heterozygous) and wide-type
      mice. Similar infarct volumes and neurological deficits were seen among mice of
      different genotypes. There was no difference among the groups in arterial blood
      pressure and regional cerebral blood flow during the first 30 min of ischemia.
      Our results failed to confirm the harmful effect of losing COX-1 activity due to
      gene knockout in a permanent endovascular MCAO mouse stroke model.

PMID- 12213635
TI  - Localization of choline acetyltransferase in the developing and adult retina of
      Xenopus laevis.
AB  - In the present study the presence of choline acetyltransferase (ChAT)
      immunoreactive cells in the adult retina of Xenopus laevis was demonstrated and
      their appearance and maturation during development were examined. Two cholinergic
      amacrine cell types were identified in the retina. They were located in the
      deepest row of cells in the inner nuclear layer and in the ganglion cell layer,
      respectively. Cell processes from these cells organized distinct laminae within
      the inner plexiform layer. ChAT immunoreactivity was first observed at embryonic
      stage 35 coinciding with the onset of vision and increased rapidly in
      premetamorphosis as synaptogenesis and growth proceeded. The development of both
      ChAT cell populations occurred simultaneously and cells that expressed ChAT
      transiently were not observed. Our results contrast with previous studies that
      suggested a late involvement of acetylcholine in the retina of Xenopus and
      support the notion that, like in mammals, this transmitter is involved in early
      phases of neurogenesis, cell migration, neuronal growth, and synaptogenesis.

PMID- 12213636
TI  - Age-related upregulation of insulin-like growth factor receptor type I in rat
      cerebellum.
AB  - We investigated age-related changes in insulin-like growth factor-I (IGF-I)
      receptor localization in the cerebellum using immunohistochemical staining. In
      adult rats, no immunoreactivity for IGF-I receptor was found in any layers of
      cerebellar cortex. In contrast, IGF-I receptor immunoreactivity was found in the
      cerebellar cortex of aged rats. The most prominent labeling was localized in the
      Purkinje cell layers and molecular layers. The cerebellar output neurons showed
      little immunoreactivity for IGF-I receptor in the nucleus medialis, interpositus
      and lateralis of adult rats. In aged cerebellar nuclei, IGF-I receptor
      immunoreactivity was observed in the surrounding neuropil. The first
      demonstration of upregulation of IGF-I receptor in aged rat cerebellum suggests
      that IGF-I may promote the survival of a degenerated population of the Purkinje
      neurons by increases in IGF-I receptor expression during aging.

PMID- 12213637
TI  - The neuroprotectant ebselen inhibits oxidative DNA damage induced by dopamine in
      the presence of copper ions.
AB  - Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a seleno-organic compound with
      glutathione peroxidase-like activity, has been shown to be protective against
      brain ischemic injury and Parkinson's disease. This study was undertaken to
      investigate the protective effects of ebselen on oxidative DNA damage induced by
      dopamine in the presence of copper ions. Incubation of phiX-174 plasmid DNA with
      micromolar dopamine in the presence of Cu(II) resulted in a concentration
      dependent induction of DNA strand breaks. Both a Cu(II)/Cu(I) redox cycle and
      H(2)O(2) formation were critically involved in the induction of DNA strand breaks
      by the dopamine/Cu(II) system. The presence of ebselen at micromolar
      concentrations led to a marked concentration-dependent inhibition of DNA strand
      breaks induced by the dopamine/Cu(II) system. Further studies showed that ebselen
      did not affect either the Cu(II)-mediated oxidation of dopamine to dopamine
      quinone or the reduction of Cu(II) to Cu(I) by dopamine. Instead, the presence of
      ebselen resulted in a marked decrease in the levels of H(2)O(2) derived from the
      Cu(II)-mediated oxidation of dopamine. Taken together, our results demonstrate
      for the first time that ebselen is able to inhibit the dopamine/Cu(II)-induced
      oxidative DNA damage, which appears to be attributable to the ability of ebselen
      to decrease the levels of H(2)O(2) derived from the dopamine/Cu(II) system. Since
      oxidative DNA damage has been implicated in the pathogenesis of various
      neurodegenerative diseases, the inhibition of oxidative DNA damage by ebselen may
      be responsible, at least partially, for its neuroprotective activities observed
      in both humans and experimental animals.

PMID- 12213638
TI  - Extracellular putrescine content after acute excitotoxic brain damage in the rat.
AB  - We examined the effects of the local infusion of kainic acid (KA), by reverse
      dialysis in the rat striatum, on the concentration of polyamines in the
      extracellular striatal compartment and in tissue. KA infusion markedly increased
      (3-fold) extracellular putrescine (PUT) concentration, which reached its maximum
      at the end of the dialysis experiments (6 h). Tissue PUT concentration was also
      increased (2-fold) in the striatum perfused with KA but not in the contralateral
      side. Extracellular spermidine (SD) concentration but not tissue SD concentration
      was affected by KA. The increase in PUT was accompanied by histological damage
      around the probe and by an increase in ornithine decarboxylase content, as
      assessed by immunohistochemistry. These results indicate that in the first stages
      of the excitotoxic lesion, there is an increase in the extracellular
      concentrations of PUT and SD.

PMID- 12213639
TI  - Baroreceptor-related dysrhythmias in piglets with selective autonomic denervation
      of the heart.
AB  - This study was carried out to determine whether selective cardiac autonomic
      denervation performed on neonatal swine would evoke dysrhythmias later in
      development. Piglets (n = 27; 5-10 days old) underwent unilateral stellate
      ganglion ablation, or right cardiac vagotomy, or sham surgery. Fifty to sixty
      days after denervation, acute experiments were performed to evaluate responses to
      baroreceptor activation. Of all animals who exhibited prolonged R-R intervals,
      only those with right stellate ganglion ablation had prolonged corrected QT
      intervals. Despite findings suggesting an arrhythmogenic state (predominance of
      left-sided cardiac innervation), dysrhythmias occurred in all animals with
      stellate ganglion ablation, regardless of laterality, but in few vagotomized or
      control animals. Our results suggest that partial sympathetic innervation may
      alter cardiac function so that dysrhythmias are more likely to occur during
      baroreceptor activation.

PMID- 12213640
TI  - A clinical and neuropathological study of an unusual case of sporadic tauopathy.
      A variant of corticobasal degeneration?
AB  - We report a sporadic case of tauopathy with unusual clinical and
      neuropathological features. The patient presented with progressive symmetric
      rigid-akinetic parkinsonism and dementia of the subcortical type. Magnetic
      resonance imaging of the brain revealed atrophy resembling multiple system
      atrophy. The level of cerebrospinal fluid tau protein phosphorylated at serine
      199 was markedly elevated. The autopsy revealed more glial than neuronal
      tauopathy, with much heavier involvement of subcortical white matter and the
      brainstem than of the cerebral cortex. Analysis of dephosphorylated tau revealed
      that hyperphosphorylated four-repeat tau isoforms were deposited in the brain of
      the patient. Despite morphological and biochemical resemblance to a certain form
      of familial fronto-temporal dementia, no mutation of the tau gene including exon
      10 could be found. Our findings, taken together with those in previous similar
      case reports, indicate that the case represents an atypical form of corticobasal
      degeneration or a new variant of sporadic tauopathy.

PMID- 12213641
TI  - Induced expression of early response genes/oxidative injury in rat
      pheochromocytoma (PC12) cell line by 6-hydroxydopamine: implication for
      Parkinson's disease.
AB  - The expression of early response gene proteins c-Fos, c-Jun, and GAP-43 and their
      association with 6-hydroxydopamine (6-OHDA)-mediated oxidative injury were
      investigated using catecholaminergic PC12 cell line. Significant induction in the
      expression of c-Fos (P < 0.01), c-Jun (P < 0.001) and GAP-43 (P < 0.05) was
      observed following 2 h exposure to 6-OHDA (10(-6) M), which persisted during 24 h
      of observation. The exposed cells exhibited an increase in lipid peroxidation
      (48, 59 and 33%) along with decreased catalase activity (49, 30 and 13%) and
      glutathione levels (39, 28 and 16%) following 24, 48 and 72 h exposure,
      respectively. A concentration-dependent functional impairment of mitochondria as
      studied by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay
      and decreased cell survival were also observed following 6-OHDA (10(-4), 10(-5)
      M) exposure for 24, 48 and 72 h. The results indicate a role of the early
      response gene in oxidative stress-mediated dopaminergic cell death by 6-OHDA.
      Similar mechanisms may also be operative in the development of Parkinson's
      disease, as an increased presence/formation of endogenous 6-OHDA has been
      reported in Parkinson's patients.

PMID- 12213642
TI  - Lipid peroxidation by nitric oxide supplements after spinal cord injury: effect
      of antioxidants in rats.
AB  - To determine the extent to which exogenous nitric oxide (NO) might affect
      hemodynamics and/or increase oxidative damage after acute spinal cord (SC)
      injury, rats were submitted to SC contusion, and given a NO donor or NO
      precursor. Intravenous isosorbide dinitrate (10 microg/kg per min) or L-arginine
      (300 mg/kg per 23 h) showed a tendency to increase lipid peroxidation (LP),
      although without reaching significance compared to non-treated injured rats 24 h
      post-injury, and without affecting mean arterial pressure and heart rate
      importantly. LP due to injury and exogenous NO was significantly inhibited by the
      co-administration of a cocktail of antioxidants (12 mg/kg superoxide dismutase
      mimetic, 27000 U/kg catalase, and 12 mg/kg glutathione), but less effectively for
      the injury-L-arginine condition. These results demonstrate that in order to
      further test the potential neuroprotective effect of NO enhancing reagents after
      SC injury, antioxidants must be included in the treatment scheme.

PMID- 12213643
TI  - Beta-amyloid deposition and neurofibrillary tangle association with caspase
      activation in Down syndrome.
AB  - Individuals with Down syndrome (DS) and Alzheimer's disease (AD) develop senile
      plaques, neurofibrillary tangles (NFT), and neuron loss. Recent studies
      demonstrate the activation of apoptotic pathways in AD; less data is available in
      DS. The DS brain was examined using immunocytochemistry and antibodies against
      the active fragment of caspase-8 (AC, 8) and to caspase-3 cleavage products of
      fodrin (CCP), a neuronal cytoskeleton protein. The hippocampus demonstrated
      widespread accumulation of fodrin CCP and AC8 in NFTs and dystrophic neurites.
      Individual neurons contained intracellular beta-amyloid (Abeta) and fodrin CCP
      providing evidence that caspase activation can occur with both NFT and Abeta.
      Abeta within or around neurons in addition to contributing to NFT formation may
      also trigger apoptotic pathways. Caspase activation may lead to the cleavage of
      critical cellular proteins and neuronal cell death associated with DS.

PMID- 12213644
TI  - Changes of calretinin, calbindin D28K and parvalbumin-immunoreactive neurons in
      the superficial layers of the hamster superior colliculus following monocular
      enucleation.
AB  - We studied the effects of monocular enucleation on the patterned distribution of
      calretinin-, calbindin D28K- and parvalbumin-immunoreactive (IR) neurons in the
      superficial layers of the hamster superior colliculus (SC). The calcium-binding
      proteins were localized using antibody immunocytochemistry. Almost complete
      depletion of the calretinin-IR fibers in the superficial layers of the
      contralateral SC was found following unilateral enucleation. Quantitative
      analysis showed that on the experimental side of the SC, an enormous number of
      calretinin-IR cells newly appeared (716%). On the experimental side of the SC,
      the number of parvalbumin-IR cells also increased (32%). By contrast, on the
      experimental side of the SC, the number of calbindin D28K-IR cells exhibited a
      reduction (43%). Two-color immunofluorescence revealed that none of the newly
      appeared calretinin-IR cells were labeled with antibodies to calbindin D28K or
      parvalbumin. The present results demonstrate that retinal projection may control
      the activity of the expression of these calcium-binding proteins in the hamster
      SC but in different manners. The results also show that the patterned change of
      calretinin and parvalbumin in the hamster SC is comparable with other animals,
      but the change of calbindin D28K is not identical.

PMID- 12213645
TI  - NaX sodium channel is expressed in non-myelinating Schwann cells and alveolar
      type II cells in mice.
AB  - Na(x) is an extracellular sodium-level-sensitive sodium channel expressed in the
      circumventricular organs in the brain, essential loci for the sodium-level
      homeostasis in body fluids. Here, we examined the localization of Na(x)
      throughout the visceral organs at the cellular level. In visceral organs
      including lung, heart, intestine, bladder, kidney and tongue, a subset of Schwann
      cells within the peripheral nerve trunks were highly positive for Na(x). An
      electron microscopic study indicated that these Na(x)-positive cells were non
      myelinating Schwann cells. In the lung, Na(x)-positive signals were also observed
      in the alveolar type II cells, which actively absorb sodium and water to aid gas
      exchange through the alveolar surface. It was thus suggested that the Na(x)
      sodium channel is involved in controlling the local extracellular sodium level
      through sodium absorption activity.

PMID- 12213646
TI  - Immature-like astrocytes are associated with dentate granule cell migration in
      human temporal lobe epilepsy.
AB  - In human temporal lobe epilepsy, a dispersion of dentate granule cells is
      frequently described in adults who had an early risk factor. To elucidate the
      role of glia in this phenomenon, we investigated neuronal dispersion, astrocyte
      organization and expression of intermediate filaments of mature and immature
      astrocytes (i.e. glial fibrillary acidic protein (GFAP) and vimentin,
      respectively) in seven subjects with early febrile seizures (F(+)) and five
      subjects with other etiologies than febrile seizures (F(-)). Compared to F(-)
      patients, a majority of F(+) subjects showed neuronal dispersion and vimentin
      expression in radial glia. However, in two patients with the maximal dispersion,
      radial processes expressed only GFAP. We suggest that granule cell migration that
      occurs in adult epileptic focus results from the transient occurrence of immature
      like glia throughout the granular layer.

PMID- 12213647
TI  - Clomipramine treatment in neonatal rats alters the brain acetylcholinesterase
      activity in adulthood.
AB  - The enzyme, acetylcholinesterase, activity of the brain was measured in control
      and clomipramine-induced behaviorally depressed rats. Compared with control rats,
      the soluble form of acetylcholinesterase activity of the depressed rats was 31.8%
      higher in the hippocampus and 26.0% lower in the frontal cortex. However, the
      activity of soluble form of this enzyme was not significantly different in the
      hypothalamus, septum, and brainstem. These results suggest for the first time
      that the altered cholinergic activity in the specific areas of the brain may be
      involved in the behavioral depression observed in the rat model of human
      endogenous depression.

PMID- 12213648
TI  - Nicotine suppresses 1-methyl-4-phenylpyridinium ion-induced hydroxyl radical
      generation in rat striatum.
AB  - The present study examined the ability of antioxidant effects of nicotine on 1
      methyl-4-phenylpyridinium ion (MPP(+))-induced hydroxyl radical (*OH) formation
      of rat striatum. Rats were anesthetized and sodium salicylate in Ringer's
      solution (0.5 nmol/microl per min) was infused through a microdialysis probe to
      detect the generation of.OH as reflected by non-enzymatic formation trapped as
      2,3-dihydroxybenzoic acid (DHBA) in the striatum. MPP(+) enhanced generation
      of.OH formation trapped as DHBA. However, nicotine (100 microM) significantly
      suppressed.OH formation induced by MPP(+). Iron (II) (2, 5 and 10 microM)
      increased the levels of DHBA in a concentration-dependent manner. However, in the
      presence of nicotine (100 microM), the effect of nicotine was suppressed. These
      results suggest that nicotine has a preventive effect on.OH generation by MPP(+)
      in rat striatum.

PMID- 12213650
TI  - Introduction to the special issue: transcription elongation control.

PMID- 12213651
TI  - Elongation by RNA polymerase II: structure-function relationship.
AB  - RNA polymerase II is the eukaryotic enzyme that transcribes all the mRNA in the
      cell. Complex mechanisms of transcription and its regulation underlie basic
      functions including differentiation and morphogenesis. Recent evidence indicates
      the process of RNA chain elongation as a key step in transcription control.
      Elongation was therefore expected and found to be linked to human diseases. For
      these reasons, major efforts in determining the structures of RNA polymerases
      from yeast and bacteria, at rest and as active enzymes, were undertaken. These
      studies have revealed much information regarding the processes involved in
      transcription. Eukaryotic RNA polymerases and their homologous bacterial
      counterparts are flexible enzymes with domains that separate DNA and RNA, prevent
      the escape of nucleic acids during transcription, allow for extended pausing or
      "arrest" during elongation, allow for translocation of the DNA and more.
      Structural studies of RNA polymerases are described below within the context of
      the process of transcription elongation, its regulation and function.

PMID- 12213652
TI  - Promoter clearance and escape in prokaryotes.
AB  - Promoter escape is the last stage of transcription initiation when RNA
      polymerase, having initiated de novo phosphodiester bond synthesis, must begin to
      relinquish its hold on promoter DNA and advance to downstream regions (DSRs) of
      the template. In vitro, this process is marked by the release of high levels of
      abortive transcripts at most promoters, reflecting the high instability of
      initial transcribing complexes (ITCs) and indicative of the existence of barriers
      to the escape process. The high abortive initiation level is the result of the
      existence of unproductive ITCs that carry out repeated initiation and abortive
      release without escaping the promoter. The formation of unproductive ITCs is a
      widespread phenomenon, but it occurs to different extent on different promoters.
      Quantitative analysis of promoter mutations suggests that the extent and pattern
      of abortive initiation and promoter escape is determined by the sequence of
      promoter elements, both in the promoter recognition region (PRR) and the initial
      transcribed sequence (ITS). A general correlation has been found that the
      stronger the promoter DNA-polymerase interaction, the poorer the ability of RNA
      polymerase to escape the promoter. In gene regulation, promoter escape can be the
      rate-limiting step for transcription initiation. An increasing number of
      regulatory proteins are known to exert their control at this step. Examples are
      discussed with an emphasis on the diverse mechanisms involved. At the molecular
      level, the X-ray crystal structures of RNA polymerase and its various
      transcription complexes provide the framework for understanding the functional
      data on abortive initiation and promoter escape. Based on structural and
      biochemical evidence, a mechanism for abortive initiation and promoter escape is
      described.

PMID- 12213653
TI  - Promoter escape by RNA polymerase II.
AB  - Transcription of protein-coding genes is one of the most fundamental processes
      that underlies all life and is a primary mechanism of biological regulation. In
      eukaryotic cells, transcription depends on the formation of a complex at the
      promoter region of the gene that minimally includes RNA polymerase II and several
      auxiliary proteins known as the general transcription factors. Transcription
      initiation follows at the promoter site given the availability of nucleoside
      triphosphates and ATP. Soon after the polymerase begins the synthesis of the
      nascent mRNA chain, it enters a critical stage, referred to as promoter escape,
      that is characterized by physical and functional instability of the transcription
      complex. These include formation of abortive transcripts, strong dependence on
      ATP cofactor, the general transcription factor TFIIH and downstream template.
      These criteria are no longer in effect when the nascent RNA reaches a length of
      14-15 nucleotides. Towards the end of promoter escape, disruption or adjustment
      of protein-protein and protein-DNA interactions, including the release of some of
      the general transcription factors from the early transcription complex is to be
      expected, allowing the transition to the elongation stage of transcription. In
      this review, we examine the experimental evidence that defines promoter escape as
      a distinct stage in transcription, and point out areas where critical information
      is missing.

PMID- 12213654
TI  - The many conformational states of RNA polymerase elongation complexes and their
      roles in the regulation of transcription.
AB  - Transcription is highly regulated both by protein factors and by specific RNA or
      DNA sequence elements. Central to this regulation is the ability of RNA
      polymerase (RNAP) to adopt multiple conformational states during elongation. This
      review focuses on the mechanism of transcription elongation and the role of
      different conformational states in the regulation of elongation and termination.
      The discussion centers primarily on data from structural and functional studies
      on Escherichia coli RNAP. To introduce the players, a brief introduction to the
      general mechanism of elongation, the regulatory proteins, and the conformational
      states is provided. The role of each of the conformational states in elongation
      is then discussed in detail. Finally, an integrated mechanism of elongation is
      presented, bringing together the panoply of experiments.

PMID- 12213655
TI  - Transcription attenuation.
AB  - In this review, we describe a variety of mechanisms that bacteria use to regulate
      transcription elongation in order to control gene expression in response to
      changes in their environment. Together, these mechanisms are known as attenuation
      and antitermination, and both involve controlling the formation of a
      transcription terminator structure in the RNA transcript prior to a structural
      gene or operon. We examine attenuation and antitermination from the point of view
      of the different biomolecules that are used to influence the RNA structure.
      Attenuation of many amino acid biosynthetic operons, particularly in enteric
      bacteria, is controlled by ribosomes translating leader peptides. RNA-binding
      proteins regulate attenuation, particularly in gram-positive bacteria such as
      Bacillus subtilis. Transfer RNA is also used to bind to leader RNAs and influence
      transcription antitermination in a large number of amino acyl tRNA synthetase
      genes and several biosynthetic genes in gram-positive bacteria. Finally,
      antisense RNA is involved in mediating transcription attenuation to control copy
      number of several plasmids.

PMID- 12213656
TI  - Rho-dependent termination and ATPases in transcript termination.
AB  - Transcription factor Rho is a ring-shaped, homohexameric protein that causes
      transcript termination through actions on nascent RNAs that are coupled to ATP
      hydrolysis. The Rho polypeptide has a distinct RNA-binding domain (RNA-BD) of
      known structure as well as an ATP-binding domain (ATP-BD) for which a structure
      has been proposed based on homology modeling. A model is proposed in which Rho
      first makes an interaction with a nascent RNA on a C-rich, primarily single
      stranded rut region of the transcript as that region emerges from the exit site
      of RNA polymerase. A subsequent step involves a temporary release of one subunit
      of the hexamer to allow the 3' segment of the nascent transcript to enter the
      central channel of the Rho ring. Actions of the Rho structure in the channel on
      the 3' segment that are coupled to ATP hydrolysis pull the RNA from its contacts
      with the template and RNA polymerase, thus causing termination of its synthesis.

PMID- 12213657
TI  - Regulation of transcription elongation by phosphorylation.
AB  - The synthesis of mRNA by RNA polymerase II (RNAPII) is a multistep process that
      is regulated by different mechanisms. One important aspect of transcriptional
      regulation is phosphorylation of components of the transcription apparatus. The
      phosphorylation state of RNAPII carboxy-terminal domain (CTD) is controlled by a
      variety of protein kinases and at least one protein phosphatase. We discuss
      emerging genetic and biochemical evidence that points to a role of these factors
      not only in transcription initiation but also in elongation and possibly
      termination. In addition, we review phosphorylation events involving some of the
      general transcription factors (GTFs) and other regulatory proteins. As an
      interesting example, we describe the modulation of transcription associated
      kinases and phosphatase by the HIV Tat protein. We focus on bringing together
      recent findings and propose a revised model for the RNAPII phosphorylation cycle.

PMID- 12213658
TI  - Transcript elongation on a nucleoprotein template.
AB  - Chromatin forms a general, repeating barrier to elongation of transcripts by
      eukaryotic RNA polymerases. Recent studies of nucleosome structure and histone
      modifications reveal a set of likely mechanisms for control of elongation through
      chromatin. Genetic and biochemical studies of transcription have identified a set
      of accessory factors for transcript elongation by RNA polymerase II (Pol II) that
      appear to function in the context of chromatin. The C-terminal repeated domain
      (CTD) of Pol II may also play a role in regulating elongation through chromatin.

PMID- 12213659
TI  - Promoting elongation with transcript cleavage stimulatory factors.
AB  - Transcript elongation by RNA polymerase is a dynamic process, capable of
      responding to a number of intrinsic and extrinsic signals. A number of elongation
      factors have been identified that enhance the rate or efficiency of
      transcription. One such class of factors facilitates RNA polymerase transcription
      through blocks to elongation by stimulating the polymerase to cleave the nascent
      RNA transcript within the elongation complex. These cleavage factors are
      represented by the Gre factors from prokaryotes, and TFIIS and TFIIS-like factors
      found in archaea and eukaryotes. High-resolution structures of RNA polymerases
      and the cleavage factors in conjunction with biochemical investigations and
      genetic analyses have provided insights into the mechanism of action of these
      elongation factors. However, there are yet many unanswered questions regarding
      the regulation of these factors and their effects on target genes.

PMID- 12213660
TI  - RNA polymerase II conducts a symphony of pre-mRNA processing activities.
AB  - RNA polymerase II (RNAP II) and its associated factors interact with a diverse
      collection of nuclear proteins during the course of precursor messenger RNA
      synthesis. This growing list of known contacts provides compelling evidence for
      the existence of large multifunctional complexes, a.k.a. transcriptosomes, within
      which the biosynthesis of mature mRNAs is coordinated. Recent studies have
      demonstrated that the unique carboxy-terminal domain (CTD) of the largest subunit
      of RNAP II plays an important role in recruiting many of these activities to the
      transcriptional machinery. Throughout the transcription cycle the CTD undergoes a
      variety of covalent and structural modifications which can, in turn, modulate the
      interactions and functions of processing factors during transcription initiation,
      elongation and termination. New evidence suggests that the possibility that
      interaction of some of these processing factors with the polymerase can affect
      its elongation rate. Besides the CTD, proteins involved in pre-mRNA processing
      can interact with general transcription factors (GTFs) and transcriptional
      activators, which associate with polymerase at promoters. This suggests a
      mechanism for the recruitment of specific processing activities to different
      transcription units. This harmonic integration of transcriptional and post
      transcriptional activities, many of which once were considered to be functionally
      isolated within the cell, supports a general model for the coordination of gene
      expression by RNAP II within the nucleus.

PMID- 12213661
TI  - Regulation of viral transcription elongation and termination during vaccinia
      virus infection.
AB  - Vaccinia virus provides a useful genetic and biochemical tool for studies of the
      basic mechanisms of eukaryotic transcription. Vaccinia genes are transcribed in
      three successive gene classes during infection, early, intermediate, and late.
      Vaccinia transcription is regulated primarily by virus gene products not only
      during initiation, but also during elongation and termination. The factors and
      mechanisms regulating early elongation and termination differ from those
      regulating intermediate and late gene expression. Control of transcription
      elongation and termination in vaccinia virus bears some similarity to the same
      process in other prokaryotic and eukaryotic systems, yet features some novel
      mechanisms as well.

PMID- 12213662
TI  - Transcriptional control of the RNA-dependent RNA polymerase of vesicular
      stomatitis virus.
AB  - The nonsegmented negative strand (NNS) RNA viruses include some of the mosr
      problematic human, animal and plant pathogens extant: for example, rabies virus,
      Ebola virus, respiratory syncytial virus, the parainfluenza viruses, measles and
      infectious hemapoietic necrosis virus. The key feature of transcriptional control
      in the NNS RNA viruses is polymerase entry at a single 3' proximal site followed
      by obligatory sequential transcription of the linear array of genes. The levels
      of gene expression are primarily regulated by their position on the genome. The
      promoter proximal gene is transcribed in greatest abundance and each successive
      downstream gene is synthesized in progressively lower amounts due to attenuation
      of transcription at each successive gene junction. In addition, NNS RNA virus
      gene expression is regulated by cis-acting sequences that reside at the beginning
      and end of each gene and the intergenic junctions. Using vesicular stomatitis
      virus (VSV), the prototypic NNS, many of these control elements have been
      identified.The signals for transcription initiation and 5' end modification and
      for 3' end polyadenylation and termination have been elucidated. The sequences
      that determine the ability of the polymerase to slip on the template to generate
      polyadenylate have been identified and polyadenylation has been shown to be
      template dependent and integral to the termination process. Transcriptional
      termination is a key element in control of gene expression of the negative strand
      RNA viruses and a means by which expression of individual genes may be silenced
      or regulated within the framework of a single transcriptional promoter. In
      addition, the fundamental question of the site of entry of the polymerase during
      transcription has been reexamined and our understanding of the process altered
      and updated. The ability to engineer changes into infectious viruses has
      confirmed the action of these elements and as a consequence, it has been shown
      that transcriptional control is key to controlling the outcome of a viral
      infection. Finally, the principles of transcriptional regulation have been
      utilized to develop a new paradigm for systematic attenuation of virulence to
      develop live attenuated viral vaccines.

PMID- 12213663
TI  - Anorexia nervosa in female adolescents: endocrine and bone mineral density
      disturbances.
AB  - Anorexia nervosa (AN) is a chronic childhood psychiatric illness that involves a
      reduction in caloric intake, loss of weight and amenorrhea, either primary or
      secondary. The diagnostic criteria for AN have been established by the American
      Psychiatric Association. The prevalence of this disease amongst adolescents and
      young adults is between 0.5 and 1% and the incidence of new cases per year is
      approximately 5-10/100,000 between 15 and 19 years of age.A number of endocrine
      and metabolic disturbances have been described in patients with AN including
      amenorrhea-oligomenorrhea, delayed puberty, hypothyroidism, hypercortisolism, IGF
      I deficiency, electrolyte abnormalities, hypoglycemia and hypophosphatemia, among
      others. In addition to prolonged amenorrhea, osteopenia and osteoporosis are the
      most frequent complications leading to clinically relevant fractures and
      increased fracture risk throughout life. Patients exhibit an alteration in the
      hypothalamic-pituitary-gonadal axis, which is responsible for the menstrual
      disorders. The increase in gonadotropin secretion that can be observed after
      ponderal recuperation suggests that malnutrition could be the most important
      mechanism involved in the decrease in gonadotropin secretion. The loss of fat
      tissue as a consequence of nutrient restriction has been associated with
      hypoleptinemia and abnormal secretion of peptides implicated in food control
      (neuropeptide Y, melanocortins and corticotropin-releasing factor, among
      others).A review of the endocrine abnormalities, disturbances in
      neurotransmitters, as well as a detailed analysis of bone markers and bone
      mineral density in patients with AN is described.

PMID- 12213664
TI  - Oncogenic mutations in the thyrotropin receptor of autonomously functioning
      thyroid nodules in the Japanese population.
AB  - OBJECTIVE: Constitutively activating mutations of the thyrotropin receptor (TSHR)
      have been found in the majority of autonomously functioning thyroid nodules
      (AFTNs) in European patients. The reported frequency of these mutations varies
      among reports but amounts to 50-80%. To date, only one such mutation responsible
      for AFTNs has been identified in the Japanese population and the pathogenic role
      of such mutations in Japanese AFTNs has been questioned. In the present study, we
      evaluated the frequency of activating mutations in the TSHR and G(alpha)s in 10
      Japanese AFTNs. DESIGN: Genomic DNA was extracted from fresh frozen tissue. The
      TSHR and the almost entire sequence of the gene coding for the alpha subunit of
      Gs have been amplified and sequenced. RESULTS: In sequence analysis, four
      mutations in the TSHR (T632A, I486M, M453T and L512R) were found. To complete our
      analysis, we searched mutations in the gene coding for the alpha subunit of Gs,
      in the samples negative for TSHR mutations. In one case a mutation (R201H)
      affecting GTPase activity was found. CONCLUSIONS: If we focus on the solitary
      nodules, we obtain the same mutation proportion as in European patients (70%).
      The absence of TSHR and G(alpha)s mutations in a significant proportion of
      autonomous adenomas in multinodular goiters suggests that other causes may also
      play a role in the genesis of these lesions.

PMID- 12213665
TI  - Effect of iodine or iopanoic acid on thyroid Ca2+/NADPH-dependent H2O2-generating
      activity and thyroperoxidase in toxic diffuse goiters.
AB  - OBJECTIVE: The aim of the present study was to compare the effects of iopanoic
      acid (IOP) or a saturated solution of potassium iodide (SSKI) administration to
      patients with toxic diffuse goiters (TDG). DESIGN: Patients with TDG are treated
      with thionamides and high doses of iodine preoperatively. In this study, two
      types of preoperative drug regimens were used: propylthiouracil or methimazole
      plus SSKI for 10-15 days (n=8) or IOP for 7 days (n=6). METHODS: Serum thyroid
      hormones (total and free thyroxine (T(4)), total tri-iodothyronine (T(3)) and
      reverse T(3) (rT(3)), were evaluated after 7 days of either SSKI or IOP
      treatment, and after 10-15 days of SSKI administration. During thyroidectomy,
      samples of thyroid gland were obtained to evaluate thyroperoxidase and thyroid
      H(2)O(2)-generating activities. RESULTS: Serum total T(3) was significantly
      decreased after 7 days of either treatment, and serum rT(3) was significantly
      increased in IOP-treated patients. Serum total and free T(4) were unaffected by 7
      days of IOP treatment, but decreased after 7 days of SSKI treatment, although
      significantly diminished levels were only reached after a further 3-8 days of
      SSKI administration. During both drug regimens, serum TSH remained low (SSKI:
      0.159+/-0.122; IOP: 0.400+/-0.109 microU/ml). Thyroperoxidase activity was
      significantly lower in thyroid samples from patients treated with SSKI for 10-15
      days than in the thyroid glands from IOP-treated patients. However, thyroid
      H(2)O(2) generation was inhibited in samples from patients treated with either
      IOP or SSKI. CONCLUSIONS: We show herein that IOP treatment can be effective in
      the management of hyperthyroidism and that this drug inhibits thyroid NADPH
      oxidase activity, just as previously described for SSKI, probably due to its
      iodine content.

PMID- 12213666
TI  - Prevalence of diaphragmatic muscle weakness and dyspnoea in Graves' disease and
      their reversibility with carbimazole therapy.
AB  - OBJECTIVES: Dyspnoea is a common complaint among patients with thyrotoxicosis.
      However, its causative mechanisms have not been identified. We assessed the role
      of thoracic diaphragmatic muscle weakness in dyspnoea among patients with active
      Graves' disease. METHODS: Twenty-seven patients (19 female, 8 male) with active
      Graves' disease were assessed for the clinical severity of dyspnoea, functional
      (pressure generating capacity) and anatomical aspects (thickness and excursion)
      of the diaphragm at presentation. The severity of dyspnoea was assessed using a
      visual analogue scale (VAS) and the 6 min walk test. Lung function tests,
      diaphragmatic strength (sniff oesophageal pressure, SniffP(oeso)), maximum
      inspiratory and expiratory pressures, diaphragmatic thickness and movements on
      real time ultrasonography were evaluated during normal and deep respiration.
      Twenty of the 27 patients were reassessed after achieving euthyroidism with
      carbimazole therapy at a mean interval of 5+/-2 months. RESULTS: Reevaluation
      after carbimazole therapy revealed a significant reduction in dyspnoea on the VAS
      (59+/-26 to 23+/-13%). Patients covered a similar distance during the 6 min walk
      before and after euthyroidism. Significant improvement was observed in the vital
      capacity (2.57+/-0.62 to 2.94+/-0.60 l), forced expiratory volume in the first
      second (2.21+/-0.49 to 2.45+/-0.47 l), total lung capacity (3.57+/-1.19 to 4.1+/
      1.12 l), diaphragmatic movement during deep respiration (5.5+/-1.0 to 6.6+/-1.1
      cm) and SniffP(oeso) (68.7+/-23 to 93.1+/-25.2 cmH(2)O). There was no significant
      change in the distance walked in 6 min, tidal volume, lung diffusion capacity and
      diaphragmatic thickness. There was no significant correlation between the net
      change in dyspnoea score and net change in lung function tests, diaphragmatic
      movement and SniffP(oeso). CONCLUSIONS: Significant functional weakness of
      diaphragm muscle is present in patients with active Graves' disease. This
      weakness is more marked during a maximal respiratory manoeuvre, indicating a
      diminished diaphragmatic reserve which could be the cause of dyspnoea observed on
      exertion among patients with thyrotoxicosis.

PMID- 12213667
TI  - Primary thyroid disorders in endogenous Cushing's syndrome.
AB  - OBJECTIVE: To study the prevalence of primary thyroid disorders in patients who
      underwent endogenous hypercortisolism. DESIGN: Retrospective evaluation of 59
      patients with Cushing's syndrome (CS) who had, at least, a record of thyroid
      palpation by expert endocrinologists and basal measurements of TSH by second
      generation assays. When available, tri-iodothyronine and thyroxine serum levels,
      TRH-TSH tests and anti-thyroid antibodies were also analyzed. There were two age-
      and gender-matched control groups. The 'goiter control group' comprised 118
      healthy subjects who underwent thyroid palpation. The 'antibody control group'
      was composed of 40 individuals who attended the blood bank of our hospital.
      Antibodies against thyroperoxidase and measurements of TSH were analyzed in their
      blood samples. METHODS: Available files of 83 CS patients admitted to our
      endocrine unit from 1985 to 1998 were examined. Fifty-nine patients (52 women and
      7 men) with a mean age of 36.2 years (range 14-61 years) met the above
      requirements. Diagnosis of hypercortisolism had been established by a standard 1
      mg overnight dexamethasone suppression test and urinary free cortisol (UFC).
      Etiological diagnosis involved dynamic testing, measurements of ACTH levels and
      imaging techniques. After treatment, all but one of the patients were cured or
      controlled of their hypercortisolism. This was established by the finding of
      subnormal serum cortisol concentrations and/or subnormal 24-h UFC levels. Primary
      thyroid disorders were defined by the presence of one or more of the following
      diagnostic criteria: (i) goiter, (ii) positive anti-thyroid antibodies and/or
      (iii) primary thyroid function abnormalities. RESULTS: Eighteen (30.5%) patients
      had goiter (diffuse in 78% and nodular in 22%), 14 (23.7%) had primary
      subclinical hypothyroidism and 5 (8.4%) had hyperthyroidism. In 41 patients
      evaluated for antithyroid antibodies, it was found that 23 (56.1%) had positive
      titers. In a group of patients in which thyroid autoantibodies were measured both
      before and after resolution of hypercortisolism, prevalences of positive titers
      were 26.7% and 86.7% respectively (P=0.001). The overall frequency of primary
      thyroid abnormalities in our patients with Cushing's syndrome was 55.9%.
      CONCLUSIONS: Patients with endogenous Cushing's syndrome exhibit a remarkably
      high prevalence of primary thyroid disease. Resolution of hypercortisolism seems
      to trigger the development of autoimmune thyroid disorders in presumably
      predisposed subjects.

PMID- 12213668
TI  - Involvement of the MEN1 gene locus in familial isolated hyperparathyroidism.
AB  - BACKGROUND: Familial isolated hyperparathyroidism (FIHP) is a hereditary disorder
      characterised by uni- or multiglandular parathyroid disease. A subset of families
      are likely to be genetic variants of other familial tumour syndromes in which
      PHPT is the main feature, for example multiple endocrine neoplasia type 1 (MEN 1)
      and the hyperparathyroidism-jaw tumour syndrome (HPT-JT). OBJECTIVE: To
      investigate seven families diagnosed with FIHP, each with two to eight affected
      family members, to clarify the underlying genetic mechanism. METHODS: The entire
      MEN1 gene was sequenced for germline mutations and, in addition, tumour specimens
      were analysed in comparative genomic hybridisation and loss of heterozygosity
      studies. RESULTS: Two families exhibited MEN1 mutations, L112V and 1658delG,
      which were associated with loss of the wild-type 11q13 alleles in all tumours
      analysed. In the remaining five families, no MEN1 mutation was identified.
      CONCLUSION: These results support the involvement of the MEN1 tumour suppressor
      gene in the pathogenesis of some of the FIHP kindreds. However, loss on
      chromosome 11 was seen in all tumours exhibiting somatic deletions, although in
      two families the tumour deletions involved 11q distal to MEN1. We conclude that
      the altered MEN1 gene function is of importance in the development of FIHP.

PMID- 12213669
TI  - An improved computational method to assess pituitary responsiveness to
      secretagogue stimuli.
AB  - OBJECTIVE: The quantitative assessment of gland responsiveness to exogenous
      stimuli is typically carried out using the peak value of the hormone
      concentrations in plasma, the area under its curve (AUC), or through
      deconvolution analysis. However, none of these methods is satisfactory, due to
      either sensitivity to measurement errors or various sources of bias. The
      objective was to introduce and validate an easy-to-compute responsiveness index,
      robust in the face of measurement errors and interindividual variability of
      kinetics parameters. DESIGN: The new method has been tested on responsiveness
      tests for the six pituitary hormones (using GH-releasing hormone, thyrotrophin
      releasing hormone, gonadotrophin-releasing hormone and corticotrophin-releasing
      hormone as secretagogues), for a total of 174 tests. Hormone concentrations were
      assayed in six to eight samples between -30 min and 120 min from the stimulus.
      METHODS: An easy-to-compute direct formula has been worked out to assess the
      'stimulated AUC', that is the part of the AUC of the response curve depending on
      the stimulus, as opposed to pre- and post-stimulus spontaneous secretion. The
      weights of the formula have been reported for the six pituitary hormones and some
      popular sampling protocols. RESULTS AND CONCLUSIONS: The new index is less
      sensitive to measurement error than the peak value. Moreover, it provides results
      that cannot be obtained from a simple scaling of either the peak value or the
      standard AUC. Future studies are needed to show whether the reduced sensitivity
      to measurement error and the proportionality to the amount of released hormone
      render the stimulated AUC indeed a valid alternative to the peak value for the
      diagnosis of the different pathophysiological states, such as, for instance, GH
      deficits.

PMID- 12213670
TI  - Reduced microvascular perfusion and reactivity in adult GH deficient patients is
      restored by GH replacement.
AB  - BACKGROUND: An increased cardiovascular risk and mortality in hypopituitary
      patients receiving conventional hormonal treatment without GH replacement have
      been shown in several studies. Various atherogenic risk factors including
      endothelial dysfunction - an early event in the atherogenesis - are more
      expressed in adults with GH-deficiency (GHD). Changes in microcirculation and
      vascular reactivity could represent an early marker of developing vascular
      changes. OBJECTIVE: To evaluate the microcirculation and vascular reactivity in a
      GHD state before and during GH replacement. SUBJECTS, METHODS AND DESIGN:
      Thirteen adult patients (ten men, mean age 40+/-9 years) with severe GHD were
      studied. The skin microvascular perfusion and reactivity were measured by laser
      Doppler flowmetry on the forearm. Two dynamic tests for vascular perfusion and
      reactivity were used - postocclusive reactive hyperemia (PORH) and thermal
      hyperemia (TH) at 44 degrees C. Measurements were performed before and after 6
      and 12 months on GH replacement with a dose of GH that normalized IGF-I serum
      levels. The parameters of tissue perfusion and vascular reactivity measured in
      GHD were compared with values during GH treatment and with the results of the
      control group. RESULTS: Peak flow during TH in GHD patients was significantly
      reduced before GH treatment when compared with healthy subjects (means+/-s.e.m.,
      68+/-6.6 vs 111+/-8.3 perfusion units (PU), P<0.001) and normalized on GH
      treatment (109+/-12.7 PU). The velocity of perfusion increase during TH before
      treatment was significantly reduced in GHD as well (0.84+/-0.07 vs 1.53+/-0.19
      PU/s, P<0.03) and normalized on GH treatment (1.38+/-0.24 PU/s). The PORH was
      also significantly reduced in GHD compared with controls (PORH(max) 414+/-63 vs
      528+/-58%, P<0.05) and during GH treatment was restored to values not different
      from controls (642+/-86%, P=NS). CONCLUSIONS: Skin microcirculation and vascular
      reactivity measured by laser-Doppler flowmetry is significantly reduced in GHD
      adults and is restored during GH replacement therapy. Reduced tissue perfusion
      and reactivity probably reflect the endothelial dysfunction in the GHD state.
      Reduced nitric oxide production and bioavailability and also other factors like
      increased sympathetic activity and reduced conversion of thyroxine to
      triiodothyronine in the GHD state can contribute to changes in microcirculation.
      Restoration of vascular reactivity by GH replacement might have favorable
      clinical consequences on the increased vascular morbidity of GHD patients.
      Reduced skin microvascular perfusion and reactivity in GHD probably contribute to
      the impaired thermoregulation - a clinical symptom of GHD.

PMID- 12213671
TI  - Effect of low-dose of recombinant human growth hormone on bone metabolism in
      elderly women with osteoporosis.
AB  - BACKGROUND: There has been increasing evidence that the growth hormone (GH)-IGF-I
      axis plays an important part in the maintenance of bone mass. However,
      controversy still exists as to the effect of GH treatment on bone mineral density
      (BMD) in elderly patients with osteoporosis. OBJECTIVE: To investigate the effect
      of low-dose GH treatment on markers of body composition and bone turnover, serum
      concentrations of IGF-I and IGF-binding proteins (IGFBPs), and BMD at the radius
      and lumbar spine in eight elderly Japanese women with osteoporosis. METHODS:
      Participants were treated with GH as a single daily subcutaneous injection (0.125
      IU/kg per week; 0.00595 mg/kg per day) for 48 weeks. RESULTS: Markers of bone
      formation and bone resorption were both increased up to 24 weeks of GH treatment.
      The bone formation markers remained increased during GH treatment, whereas the
      bone resorption markers returned to baseline values after 24 weeks of GH
      treatment. GH treatment caused a rapid (within 2 weeks) and sustained increase in
      serum IGF-I concentration. As for IGFBPs, serum concentrations of IGFBPs-2, -3
      and -4 did not change significantly during GH treatment. In contrast, GH
      treatment caused a gradual increase in serum IGFBP-5 concentration, with a
      significant increase seen 48 weeks after the start of GH treatment. Radial BMD
      seemed to be increased during the late period of GH treatment, although the
      change was not significant. Lumbar BMD did not change during GH treatment. GH
      treatment caused a significant increase in hand grip strength. None of the GH
      treated participants had new fractures and side effects such as edema and joint
      pain. Radial BMD was significantly increased after discontinuation of GH
      treatment for another 48 weeks and a similar tendency was observed at the lumbar
      spine (7.1+/-2.3% above pretreatment values for the radius and 3.6+/-2.0% for the
      lumbar spine). CONCLUSIONS: Low-dose GH treatment attenuated the decrease in
      muscle strength and bone mass in elderly women without side effects, although
      changes in nutrition and exercise might affect BMD. The present findings provide
      useful information regarding the use of low-dose GH treatment in elderly women
      with osteoporosis.

PMID- 12213672
TI  - Hormonal evaluation and mutation screening for steroid 21-hydroxylase deficiency
      in patients with unilateral and bilateral adrenal incidentalomas.
AB  - OBJECTIVE: The aims of the present study were (a) to examine the occurrence of 21
      hydroxylase gene (CYP21) mutations in patients with unilateral and bilateral
      adrenal incidentalomas and (b) to correlate the results of mutation screening
      with hormonal parameters of 21-hydroxylase deficiency. DESIGN: The frequency of
      the eight commonly occurring CYP21 mutations in blood DNA samples of 19 patients
      with bilateral, as well as in blood and tumoral tissue DNA samples of 31 patients
      with unilateral adrenal incidentalomas, was determined. In all patients, hormonal
      evaluation for 21-hydroxylase deficiency was performed using measurements of
      basal and ACTH-stimulated plasma 17-hydroxyprogesterone (17-OHP) concentrations.
      METHODS: Blood and tumoral DNA samples were analyzed by allele-specific PCR for
      the detection of the eight commonly occurring CYP21 mutations (deletion/large
      gene conversion, intron 2 splicing, Ile172Asn, exon 6 cluster, Val281Leu,
      Leu307insT, Gln318Stop and Arg356Trp mutations). Plasma 17-OHP concentrations
      were measured by radioimmunoassay. RESULTS: Of the 19 patients with bilateral
      adrenal incidentalomas, one patient had homozygous (Val281Leu) and three patients
      had heterozygous germline CYP21 mutations (Val281Leu in two cases and Arg356Trp
      in one case). Heterozygous germline CYP21 mutations were also detected in five of
      the 31 patients with unilateral adrenal incidentalomas (Ile172Asn in three cases
      and Val281Leu in two cases). Mutation screening of tumoral DNA in unilateral
      incidentalomas showed the presence of corresponding germline mutations but no
      additional somatic mutations were found. ACTH-stimulated plasma 17-OHP
      concentrations were above 1500 ng/dl in all patients with bilateral
      incidentalomas who had homozygous and heterozygous CYP21 mutations, but
      heterozygous carriers with unilateral incidentalomas had highly variable ACTH
      stimulated plasma 17-OHP levels (between 111 and 1705 ng/dl). CONCLUSIONS: These
      results suggest a similar frequency of germline CYP21 mutations in patients with
      bilateral and unilateral adrenal incidentalomas (21.1% and 16.1% respectively).
      Therefore, it cannot be ruled out that, in at least some patients, CYP21
      mutations may play a role in the pathomechanism of bilateral and unilateral
      adrenal incidentalomas. However, the lack of clear association of CYP21 mutations
      with increased ACTH-stimulated plasma l7-OHP response, especially in patients
      with unilateral incidentalomas, suggests that the effect of CYP21 mutations on
      adrenocortical tumor formation may also involve mechanism(s) independent of ACTH
      induced changes in 17-OHP secretion.

PMID- 12213673
TI  - An endocrinopathy characterized by dysfunction of the pituitary-adrenal axis and
      alopecia universalis: supporting the entity of a triple H syndrome.
AB  - We demonstrate the rare disorder of triple H syndrome in a 25-year-old man. He
      was pointed out as having short stature, at -5.9 s.d., and diagnosed as GH
      deficient at 6 years old. Approximately a year ago, he noticed systematic hair
      loss. He lost body weight by 7 kg during the last half year. He was admitted to
      Jichi Medical School Hospital because of unconsciousness. Physical findings
      showed disturbance of consciousness with Japan Coma Scale I-3. He had emaciation
      and alopecia universalis. Laboratory findings showed plasma glucose was as low as
      1.11 mmol/l. GH and ACTH deficiency with hypoadrenocorticism were clarified. His
      intelligence was in the low normal range with a WAIS IQ of 70, and anterograde
      amnesia was suggested in the presence of a little, but not significant,
      morphological change in the hippocampus on a magnetic resonance imaging scan.
      Replacement by a physiological dose of hydrocortisone normalized plasma glucose,
      and restored body weight and growth of hair during the 7 month therapeutic
      period. The present finding strongly supports a clinical entity of triple H
      syndrome, including ACTH deficiency, alopecia universalis and anterograde
      amnesia, and that there may be some variation of the triad among the subjects.

PMID- 12213674
TI  - Thyrotropin-releasing hormone regulates the diurnal variation of pyroglutamyl
      aminopeptidase II activity in the male rat adenohypophysis.
AB  - OBJECTIVE: Thyrotropin-releasing hormone (TRH) is inactivated in the
      extracellular compartment by pyroglutamyl aminopeptidase II (PPII), a narrow
      specificity ectopeptidase present in the brain and in the lactotrophs of the
      adenohypophysis. TRH and various hypothalamic/paracrine agents regulate the
      activity of PPII on the surface of adenohypophyseal cells in primary culture. The
      activity of the hypothalamic-pituitary-thyroid axis presents circadian variations
      including an increase of serum thyrotropin levels in the early hours of the day.
      The purpose of this study was to determine whether adenohypophyseal PPII activity
      fluctuates during the daytime in the male rat and the role of TRH in these
      regulatory events in vivo. RESULTS: Adenohypophyseal PPII specific activity and
      mRNA levels presented diurnal variations. A decrease in specific activity
      occurred with a minimum between 0930 and 1130 h, associated with increased serum
      thyrotropin levels. PPII mRNA levels were lowest at 0800 h. Intraperitoneal
      injection at 0800 or 1000 h of [3-Me-His(2)]-TRH, a potent agonist of the TRH
      receptor, reduced PPII specific activity at 30 min post-injection which was
      followed by a return to basal levels at 2 h. A second phase of decrease occurred
      between 4 and 8 h post-injection. Intravenous injection of a TRH-immune serum
      induced, at 2 h post-injection, an increase in adenohypophyseal PPII specific
      activity, which lasted up to 6 h. CONCLUSIONS: Adenohypophyseal PPII activity and
      mRNA levels fluctuate during the day; TRH down-regulates PPII activity in vivo,
      contributing to some of these variations. These new findings, and previous data,
      suggest that adenohypophyseal PPII activity varies in distinct physiological
      events, in response to endocrine and hypothalamic/paracrine factors, potentially
      modulating responses to TRH.

PMID- 12213675
TI  - Nerve growth factor and retinoic acid interactions in the control of small cell
      lung cancer proliferation.
AB  - OBJECTIVE: Nerve growth factor (NGF) has antiproliferative and differentiating
      effects in neuroendocrine tumors. In cell lines derived from small cell lung
      cancer (SCLC), NGF treatment stimulates NGF receptor expression, activates NGF
      secretion, inhibits proliferation and abrogates invasion. Since these effects are
      lost upon NGF withdrawal, it is relevant to identify other differentiation
      factors that may co-operate with the NGF system to control SCLC growth and
      differentiation. DESIGN: Retinoic acid (RA), which has been shown to inhibit cell
      transformation and proliferation, modulates the expression of NGF receptors and
      the sensitivity to NGF in different cell models. In the present study, we have
      investigated whether NGF and RA may interact to control the proliferation of SCLC
      cell lines. METHODS: SCLC cells were exposed to 50 ng/ml NGF or 1 microM all
      trans RA for different times. Cell proliferation was measured by the
      [(3)H]thymidine incorporation test and NGF receptor expression was evaluated by
      immunofluorescence. RESULTS: We found that RA increased the expression of both
      trkA and p75 NGF receptors in NCI-N-592 and GLC8 cell lines and prevented the
      loss of both NGF production and NGF receptor expression occurring when NGF
      treatment was discontinued. As a result, RA, which did not inhibit the
      proliferation of untreated cells, abolished NGF withdrawal-related increase in
      cell proliferation both in vitro and in vivo, thus making permanent the
      antiproliferative effects of NGF. CONCLUSIONS: These data suggest that combined
      treatments with NGF and RA or mimicking drugs may represent a strategy to be
      further investigated for the treatment of SCLC.

PMID- 12213676
TI  - Expression of growth hormone-releasing hormone in human primary endometrial
      carcinomas.
AB  - BACKGROUND: Hypothalamic GH-releasing hormone (GHRH) regulates GH release from
      the pituitary, but an ectopic production of GHRH has been detected in various non
      hypothalamic tissues, especially cancers. OBJECTIVE: To investigate whether
      endometrial tumors produce GHRH. METHODS: Twenty-four endometrioid, three serous
      papillary (SP), three mixed type endometrioid/serous papillary adenocarcinomas
      and one malignant mixed Mullerian tumor (MMMT) were assessed for GHRH
      immunoreactivity by the polyclonal anti-rabbit antibody SV95 and for the
      expression of GHRH mRNA by in situ hybridization using an oligonucleotide probe.
      RESULTS: Increased GHRH immunoreactivity was detected in 15 out of 24 (63%) of
      the endometrioid tumors, including two out of three (66%) of the mixed type
      endometrioid/serous adenocarcinomas but not in the three SP or the MMMT tumor.
      Cytoplasmic staining was detected in all positive cases, while in three of them
      strong nuclear localization of GHRH was also revealed. In situ hybridization
      indicated the presence of GHRH mRNA in six cases, all characterized as positive
      for GHRH immunoreactivity. CONCLUSION: GHRH is expressed in a subset of
      endometrial tumors, of the endometrioid type in particular. A paracrine/autocrine
      role for GHRH in the development of the disease should be considered.

PMID- 12213677
TI  - Development of an experimental ovarian tumor: immunocytochemical analysis.
AB  - OBJECTIVE: The aim of the present work was to study whether immunocytochemical
      parameters present in the normal ovary were altered after tumor development under
      high gonadotropin levels. METHODS: Ovarian tumors (luteoma): castrated female
      rats had an ovary grafted into the spleen; tumors were left to develop for 1, 2,
      3 or 7 months. The presence of apoptotic cells (TUNEL method) and the expression
      of proliferating cell nuclear antigen (PCNA), gap junction protein (Cx43),
      steroidogenic acute regulatory protein (StAR), aromatase and synaptosome
      associated protein of 25 kDa (SNAP-25) were determined by immunocytochemistry.
      Some of these findings were confirmed by RT-PCR (Cx43, StAR, SNAP-25). Inhibin
      subunit mRNAs were investigated by Northern blot. RESULTS: PCNA staining of
      tumors was mainly found in granulosa cells of transforming follicles and was
      absent from luteinized follicles. A nearly complete absence of apoptosis was
      observed. Cx43 was mainly found in follicles, while it was very weakly expressed
      or absent in luteinized follicles. StAR protein expression, indicating active
      steroidogenesis, was demonstrated only in luteinized follicles and in thecal
      cells, but was absent from granulosa cells. Aromatase immunoreactivity was very
      intense in granulosa and also present in luteal cells. Membrane-associated and
      cytoplasmic SNAP-25 immunostaining was determined in patches of endocrine cells
      in the follicles, as well as in the luteinized follicles. The expression of mRNAs
      for Cx43, StAR and SNAP-25 (RT-PCR) and inhibin subunits (Northern blots) were
      confirmed in 1-, 3- and 7-month-old tumors. CONCLUSIONS: These results indicated
      that luteoma most likely develop from unruptured follicles by hypertrophy and
      proliferation of follicular cells. Circulating gonadotropins seem to play a
      fundamental role in maintaining the expression of proteins typically expressed in
      normal ovary, while avoiding apoptosis in this tissue.

PMID- 12213678
TI  - Developmental expression and spermatogenic stage specificity of transcription
      factors GATA-1 and GATA-4 and their cofactors FOG-1 and FOG-2 in the mouse
      testis.
AB  - OBJECTIVE: The transcription factors GATA-1 and GATA-4 have been implicated in
      the regulation of testicular development and function. Their cofactors FOG-1 and
      FOG-2 are expressed in the gonads, but their cell-specific and developmental
      expression in the testis remains unresolved. Therefore, we analyzed GATA-1, GATA
      4, FOG-1 and FOG-2 expression in detail, from undifferentiated male urogenital
      ridge to adult testis. METHODS: Immunohistochemistry and in situ hybridization
      were applied on mouse testicular samples. RESULTS: GATA-4 and FOG-2, but not GATA
      1 or FOG-1, were expressed as early as in the male urogenital ridge. FOG-2
      expression was localized in the Sertoli cells at embryonal day 12.5 (E12.5), but
      it diminished with advancing fetal testicular development. In E17.5 testis, FOG-2
      was present only in the testicular capsule and a subset of fetal Leydig cells.
      FOG-1 was expressed from E15.5 Sertoli cells onwards, whereas GATA-1 was not
      detected during the fetal period at all. In the postnatal testis, FOG-2 was
      abundantly expressed immediately after birth, but in adult testis its expression
      was predominantly restricted to stage VII-XII seminiferous tubules. Stage
      specificity was also found for FOG-1, which, similarly to GATA-1, was abundantly
      expressed in stage VII-XII tubules during adulthood. CONCLUSIONS: Our results
      indicate that FOG-2, in addition to GATA-4, has a role in early gonadal
      development and sexual differentiation, and FOG-1 at later fetal stages, while
      GATA-1 executes its action postnatally. The findings suggest that, in contrast to
      the hematopoietic system and the heart, GATA-1 and GATA-4 do not use FOG-1 and
      FOG-2 respectively as their only cofactors during the early stages of testicular
      development.

PMID- 12213679
TI  - Nerve growth factor induces the re-expression of functional androgen receptors
      and p75(NGFR) in the androgen-insensitive prostate cancer cell line DU145.
AB  - BACKGROUND: One of the paracrine/autocrine factors regulating prostate growth and
      differentiation is nerve growth factor (NGF). The role of NGF and its receptors
      in the prostate, however, remains controversial. We have shown that NGF treatment
      of human prostate cancer cell lines reduced their tumorigenicity, both in vitro
      and in vivo. OBJECTIVE: To investigate the involvement of NGF as a
      differentiation factor in prostate cancer cells. DESIGN: We exposed the androgen
      independent/androgen receptor (AR)-negative prostate cancer cell line DU145 to
      NGF to study whether this neurotrophin could revert DU145 cells to a less
      malignant phenotype. METHODS: DU145 cells were treated with NGF, then ARs and NGF
      receptor p75(NGFR) expression and telomerase activity were studied. Finally, we
      investigated whether re-expression of ARs could restore the androgen sensitivity
      in this cell line. RESULTS AND CONCLUSIONS: NGF treatment induced a reversion of
      DU145 cells to a less malignant phenotype, characterized by the re-expression of
      ARs and p75(NGFR) NGF receptors. Re-expression of ARs restored the androgen
      sensitivity, as suggested by the fact that exposure to dihydrotestosterone
      stimulated the growth of NGF-treated DU145 cells. This effect was blocked by
      androgen antagonist drugs, such as hydroxyflutamide and cyproterone acetate,
      which also induced apoptotic death of NGF-treated cells. The hypothesis that a
      differentiation pathway is activated by exogenous NGF in DU145 cells is also
      supported by findings indicating that NGF-treated DU145 cells expressed a low
      telomerase activity, as a result of a decrease in human telomerase reverse
      transcriptase transcription.

PMID- 12213680
TI  - Interaction between malnutrition and ovarian hormones on the systemic IGF-I axis.
AB  - OBJECTIVE: In malnutrition both the GH-IGF and reproductive axes are greatly
      affected. Because the actions of IGF and sex steroids are inter-dependent in many
      tissues, we have examined how ovariectomy modulates the response of the systemic
      IGF system to undernutrition. DESIGN AND METHODS: Peripubertal (30 days of age)
      female rats were either sham operated or ovariectomized. Five days later half of
      each group was submitted to a protein-caloric restriction diet. All rats were
      killed at 60 days of age. RESULTS: Growth was decreased in all rats submitted to
      calorie restriction and this was consistent with a decrease in circulating IGF-I
      concentrations and liver IGF-I mRNA expression. While in normally fed rats
      ovariectomy had no significant effect on serum IGF-I concentrations,
      ovariectomized and underfed rats had significantly higher levels than intact
      underfed rats. In undernourished rats, serum IGF-binding proteins (IGFBP)-1, -2
      and -3 concentrations were significantly reduced and this was not modified by
      ovariectomy. In contrast, liver mRNA concentrations of IGFBP-1 and -2 were
      increased and IGFBP-3 unchanged in intact undernourished animals, suggesting that
      undernutrition could be affecting the proteolysis of these binding proteins, and
      this response was significantly modulated by ovariectomy. CONCLUSION: These
      results indicate that the presence of circulating ovarian hormones significantly
      affects the response of the IGF system to undernutrition.

PMID- 12213681
TI  - Rapid signal transduction in Sertoli cells.
AB  - The importance of non-genomic signaling as a complementary route for cell
      regulation has recently become evident. This rapid mechanism is utilized not just
      by peptide hormones, but also by steroids and other lipid-related substances,
      resulting in amplification and fine-tuning of the signals. The Sertoli cell is
      the principal target for hormone action in the seminiferous tubules. The
      involvement of FSH, testosterone and tri-iodothyronine (T(3)) in the
      spermatogenetic process is widely known. This paper discusses some rapid
      responses to FSH, retinol, testosterone and T(3) in the control of Sertoli cell
      function. Studies employing various methodologies and techniques are described
      and several hypotheses are considered in an attempt to explain the interactions
      of hormones with plasma membrane receptors. Recent knowledge about these new
      signaling mechanisms and cross-talk between them opens new fields of research on
      the communication and integration of the multiple hormonal signaling systems.

PMID- 12213682
TI  - Treatment and course of geriatric depression: questions raised by an evolving
      clinical science.

PMID- 12213683
TI  - Clinical trials in late-life depression: revisited.

PMID- 12213684
TI  - Influence of cognitive impairment, illness, gender, and African-American status
      on psychiatric ratings and staff recognition of depression.
AB  - OBJECTIVE: The authors examined the multivariate relationships between depression
      recognition by staff members and characteristics of nursing home residents.
      METHODS: Analyses used a simple random sample of 270 residents, drawn from six
      randomly selected nursing homes, who were evaluated by psychiatrists for
      depression and depressive symptomatology. RESULTS: African Americans were
      generally seen by psychiatrists as having less depressive symptomatology than
      residents from other ethnic groups. The data suggest that nurse aides, perhaps
      because they see residents more often or because they are less influenced by
      demographic characteristics, may be the most valid source of information about
      residents' depression. In contrast, after partialing out the degree of depression
      severity, nurses tended to overrecognize depression among African-American
      residents. Social workers underrecognized depression among residents with
      cognitive impairment and/or Parkinson disease and among women, and overrecognized
      depression among African Americans. CONCLUSION: The results underline the need
      for more training in depression recognition, particularly in distinguishing
      social from clinical phenomena and in distinguishing symptoms of dementia from
      those of depression. Equally important is further investigation of the potential
      biases associated with diagnosis and recognition of depression among African
      Americans.

PMID- 12213685
TI  - APOE epsilon4 and low cholesterol as risks for depression in a biracial elderly
      community sample.
AB  - OBJECTIVE: The epsilon4 allele of apolipoprotein (APOE) is known to be associated
      with a number of adverse health outcomes, yet the association of the allele with
      depression has not been conclusively determined. The authors explored the
      hypothesis that the epsilon4 allele is a risk factor for depression among older
      persons with a low cholesterol level (a known risk factor for depression).
      METHODS: A biracial community sample of 2,550 older African Americans and Whites
      in North Carolina was genotyped for APOE, tested for cholesterol, and evaluated
      for depression at both baseline and 4-year follow-up. RESULTS: No relationship
      was found between the epsilon4 allele and depression or low cholesterol and
      depression in either cross-sectional or longitudinal analyses. The interaction of
      the epsilon4 allele and cholesterol was also not associated with depression in
      controlled analyses. Female gender, less education, being unmarried, and
      cognitive impairment were associated with depression in cross-sectional
      controlled analyses; only cognitive impairment was associated with depression in
      longitudinal analyses. CONCLUSION: Despite the association of the epsilon4 allele
      with a number of adverse health outcomes, as well as the association between
      depression and cholesterol in previous studies, no association was found between
      epsilon4 and low cholesterol or depression in cross-sectional and longitudinal
      analyses. The interaction of epsilon4 and cholesterol was not associated with
      depression.

PMID- 12213686
TI  - Depressive symptoms and mortality in a prospective study of 2,558 older adults.
AB  - OBJECTIVE: The authors report results from a 7-year prospective study of
      depression and mortality in 2,558 Medicare recipients age 65 and older. METHODS:
      This report is based on a secondary data analysis of a randomized controlled
      trial that evaluated the cost-effectiveness of preventive services for older
      enrollees in an HMO. RESULTS: Subjects with mild-to-moderate depression at
      baseline did not have an increased risk of mortality compared with those without
      significant depression. The 3% of older adults with the most severe depressive
      syndromes, however, had significant increases in mortality, even after adjusting
      for demographics, health risk behaviors, and chronic medical disorders.
      CONCLUSION: The increase in mortality in this group of older adults was
      comparable to that in participants with chronic medical disorders such as
      emphysema or heart disease.

PMID- 12213687
TI  - Sociodemographic and clinical predictors of mortality in geriatric depression.
AB  - OBJECTIVE: It is well documented that depression and early mortality are related,
      and current research suggests that depression may influence vascular causes of
      death. The authors report on prospectively observed mortality in elderly
      depressed patients, comparing differences in sex and vascular risk. METHODS: The
      subjects were 338 patients with unipolar major depression; patients with
      neurological or other psychiatric disorders were excluded. All subjects received
      a clinical evaluation and a standardized interview to establish DSM-III
      depression diagnosis. The cohort had a mean age of 67.2 years and was followed up
      at approximately 10 years from last contact. RESULTS: Mortality was associated
      with older age, older age at depression onset, and being male. Also, in men,
      mortality was associated with higher baseline CES-D scores, and, in women, with
      having a higher vascular risk rating or late age at depression onset. CONCLUSION:
      This is the first study demonstrating a gender-by-vascular condition interaction
      effect on mortality. Women with vascular risk factors may require closer follow
      up to control vascular conditions. The relationship between greater depression
      and increased mortality risk among men is interesting, and further studies will
      be required to replicate and understand it.

PMID- 12213688
TI  - Double-blind, randomized comparison of mirtazapine and paroxetine in elderly
      depressed patients.
AB  - OBJECTIVE: Authors studied the efficacy and tolerability of mirtazapine and
      paroxetine in elderly patients with major depression during an acute phase (8
      weeks) and an extension phase (16 weeks). METHODS: Patients with major depression
      and without dementia, at least 65 years old, were eligible; they were randomized
      to mirtazapine or paroxetine once daily, with doses increasing over 42 days.
      Efficacy was assessed with the Ham-D and Clinical Global Impressions Scale, and
      tolerability was assessed from adverse events. RESULTS: Of 255 patients
      randomized, 126 on mirtazapine and 120 on paroxetine were included in the
      efficacy analysis. Differences favoring mirtazapine were observed for the mean
      change from baseline in Ham-D-17 score. Other significant differences were in the
      proportion of patients classified as responders (50% decrease from baseline Ham-D
      17 scores) at Day 14 and in remission (Ham-D-17 score of 7 or less) at Day 42.
      The median time to response was 26 days in the mirtazapine group and 40 days in
      the paroxetine group. The mirtazapine group also showed more reduction in Ham-D
      Factor I (Anxiety/Somatization) and Factor VI (Sleep Disturbance) scores.
      Efficacy of both drugs was maintained during the extension phase. Patients on
      paroxetine were more likely to discontinue therapy in the acute phase because of
      adverse events. CONCLUSION: During the first weeks of treatment, antidepressant
      effects were more pronounced in the mirtazapine group, suggesting that
      mirtazapine has an earlier onset of action. Mirtazapine also demonstrated a
      better tolerability profile and represents a valuable option for the treatment of
      depression in elderly patients.

PMID- 12213689
TI  - Time-to-remission from geriatric depression: psychosocial and clinical factors.
AB  - OBJECTIVE: The authors examined psychosocial and clinical predictors of time-to
      remission in a sample of initially clinically depressed elderly patients.
      METHODS: Using a standardized algorithm, a prospective cohort study enrolled 239
      patients undergoing treatment. Patients were followed for up to 4.5 years, until
      death or withdrawal from the study. Baseline predictor variables included
      psychosocial factors, such as four domains of social support; basic and
      instrumental activities of daily living; and clinical factors, including use of
      electroconvulsive therapy (ECT), past history of depression, comorbidities, and
      antidepressant treatment. RESULTS: Only 33% of the sample (n=79) met our
      classification for depression remission. A lack of instrumental and subjective
      social support, poor self-rated health, the use of antipsychotic medication, or
      use of an antidepressant in the last 7 days were predictors of longer time-to
      remission. Use of ECT in the last year was related to shorter time-to-remission.
      CONCLUSION: Baseline psychosocial factors were just as important, as predictors
      of depression remission, as were clinical and diagnostic variables. Interventions
      directed toward social support resources, in addition to clinical intervention,
      including the use of ECT where appropriate, are likely to improve rates of
      depression remission.

PMID- 12213690
TI  - Glucose metabolic response to total sleep deprivation, recovery sleep, and acute
      antidepressant treatment as functional neuroanatomic correlates of treatment
      outcome in geriatric depression.
AB  - OBJECTIVE: The variable speed and durability of response to antidepressant
      medications in geriatric depression is a significant clinical problem. The
      authors evaluated changes in cerebral glucose metabolism measured with positron
      emission tomography (PET) during a clinical trial designed to accelerate
      medication response by the use of one night of total sleep deprivation (TSD), and
      they asked whether changes would correlate with treatment outcome after 12 weeks
      of antidepressant treatment. METHODS: Twelve elderly, unipolar depressed patients
      underwent serial PET studies at baseline, post-TSD, post-recovery sleep (after an
      initial paroxetine dose), and after 2 weeks of paroxetine treatment. RESULTS:
      Decreased regional glucose metabolism after TSD, recovery sleep, and 2 weeks of
      treatment was associated with clinical improvement at 12 weeks. The right
      cingulate gyrus area was consistently correlated with clinical improvement across
      treatment conditions. CONCLUSION: These data indicate that the early metabolic
      alterations in the right cingulate gyrus and the persistence of these adaptive
      changes are associated with improvement in depressive symptoms.

PMID- 12213691
TI  - Quality of life in older adults receiving medications for anxiety, depression, or
      insomnia: findings from a community-based study.
AB  - OBJECTIVE: Depression and anxiety are associated with substantially reduced
      health-related quality of life (HRQoL) in healthy and medically ill adults. The
      authors examined the association between these conditions, as indicated by the
      use of antidepressant, anxiolytic, or hypnotic medications, and HRQoL parameters
      in older men and women. METHODS: This is a cross-sectional study of white, middle
      class, older (median age 75 years) men (n=533) and women (n=826) within a defined
      community setting. Short Form-36 Health Survey (SF-36) scores were compared
      between persons currently taking medicine(s) for depression, anxiety, and/or
      insomnia or none of these. RESULTS: The chronic physical illness summary score
      (dichotomized into scores of less than 2 versus 2 or more) was associated with
      significantly greater odds of perceiving oneself as ill and was also
      significantly correlated with poorer HRQoL in both men and women. Taking a
      psychotropic medication for anxiety, depression, or sleep was associated (in men
      and in women) with significantly greater odds of perceiving oneself as ill,
      before and after adjusting for age and chronic physical disorder scores. After
      these adjustments, use of medications remained significantly associated with
      lower scores on both the Physical and Mental Composite Scales of the SF-36 in
      women; a similar but nonsignificant association was seen in men. CONCLUSIONS:
      Among older, community-dwelling adults, anxiety, depression, and insomnia that
      require pharmacological treatment are associated with reductions in HRQoL that
      extend beyond the impact of comorbid physical illnesses.

PMID- 12213693
TI  - Response speed and rate of remission in primary and specialty care of elderly
      patients with depression.
AB  - OBJECTIVE: Depression treatment in primary care elderly patients has been
      inadequate, resulting in low rates of response and remission. The authors
      compared treatment remission rates and time-to-remission of elderly subjects
      enrolled in two ongoing depression treatment studies, one in primary care
      practices ("PROSPECT") and the other in an academic tertiary mental health care
      center ("MTLD-2"), in order to assess the value of standardizing and intensifying
      depression treatment in primary care elderly patients. METHODS: Authors compared
      remission rates and time to criterion endpoints via survival analysis. The 126
      PROSPECT subjects (mean age 71) included primary care patients with either
      current episodes of major depression or minor depression. The 129 MTLD-2 subjects
      (mean age 77) had single or recurrent unipolar major depression. PROSPECT
      subjects received a variety of open treatments, including the drug citalopram
      and/or interpersonal psychotherapy (IPT). Both patient and provider preferences
      influenced treatment selected. MTLD-2 subjects received more structured, open
      paroxetine treatment and IPT. RESULTS: The remission rates of PROSPECT and MTLD-2
      were 86.5% and 88.4%, respectively. Median time-to-remission in PROSPECT was
      significantly longer than in MTLD-2 (12 weeks versus 8.7 weeks). Limiting the
      survival analysis to subjects with major depression produced faster attainment of
      remission criteria. CONCLUSION: Notwithstanding these differences in speed and
      rate of symptom resolution, good treatment can work well in geriatric depression
      in the primary care sector.

PMID- 12213692
TI  - Phenomenological characteristics of poststroke depression: early- versus late
      onset.
AB  - OBJECTIVE: Authors compared poststroke major (n=17) or minor (n=28) depression
      diagnosed 3 to 6 months poststroke with major (n=16) or minor (n=22) depression
      diagnosed at 12 to 24 months to identify changes in the phenomenological
      characteristics of poststroke depression over time. METHODS: Depressive symptoms
      were divided into vegetative, psychological symptoms, and melancholic features
      elicited by the Present State Exam (PSE). Patients were also examined for
      severity of depression, social impairment, and neurological findings. RESULTS:
      Early-onset poststroke major depression was associated with a higher frequency of
      vegetative symptoms and larger lesion volume than late-onset major depression.
      Similarly, early-onset minor depression was associated with poorer social
      functioning and a higher frequency of melancholic, vegetative, and psychological
      symptoms than late-onset minor depression. CONCLUSION: These findings suggest
      that the phenomenological characteristics of both major and minor poststroke
      depression change over time and that both early-onset major and minor poststroke
      depression may result from similar etiological mechanisms provoked by brain
      injury.

PMID- 12213694
TI  - Effect of cerebrovascular risk factors on depression treatment outcome in later
      life.
AB  - OBJECTIVE: The vascular depression hypothesis posits that depression can arise in
      late life from cerebrovascular damage and that depression arising this way has a
      different clinical presentation and is more chronic and treatment-resistant than
      early-onset depression. This study tested the relationship of cerebrovascular
      risk factors (CVRF) to clinical presentation and treatment outcome in 156
      subjects enrolled in a long-term maintenance treatment study of late-life
      recurrent major depression. METHODS: CVRF scores were generated with the
      Probability of Stroke Risk Profile. Subjects with the highest one-third of scores
      were designated High CVRF, and their baseline clinical presentation and treatment
      outcomes were compared with the remaining subjects. RESULTS: In the High-CVRF
      group, a greater proportion of subjects had first-onset depression after age 60.
      However, high CVRF score, late onset of depression, and their interaction had no
      effect on time-to-remission, need for adjunctive medication, or increased risk
      for recurrence during 3-year follow-up. Furthermore, high CVRF score and late
      onset of depression did not predict the associated clinical features of vascular
      depression, such as psychomotor retardation and lack of insight, previously
      described in the literature. CONCLUSION: Optimism about the outcome of late-life
      depression treatment should not be diminished by the presence of high
      cerebrovascular risk.

PMID- 12213695
TI  - A psychometric evaluation of the Cornell Scale for Depression in Dementia in a
      frail, nursing home population.
AB  - OBJECTIVE: The authors conducted a psychometric evaluation of the Cornell Scale
      for Depression in Dementia (CSDD) through factor analysis and assessment of
      criterion validity in an older, frail nursing home population, with a secondary
      analysis of pre-intervention data from a longitudinal clinical trial aimed at
      reducing restraints in nursing homes. METHODS: The sample for the present study
      was 642 nursing home residents (mean [SD] age 84.3 [7.6] years; range: 61-105;
      82% women) with completed CSDD scores, who were interviewed immediately before
      the intervention. Nursing home residents' scores from the 19-item CSDD were
      subjected to exploratory factor analysis and criterion-validity analysis.
      RESULTS: The factor analysis resulted in four distinct clinically interpretable
      domains: Depression, Somatic/Vegetative, Disturbed Sleep, and Anxiety. Sixteen
      items were retained in these domains, and summated score indices and a global
      score were constructed. The global score and the four indices demonstrated
      adequate internal consistency and reliability. The indices generated by the
      factor analysis correlated as expected with criterion variables. CONCLUSION:
      Results suggest that in frail, institutionalized older adults with high rates of
      dementia, medical illness, and functional disability, depression measurement
      methods that are less dependent on items highly sensitive to comorbid conditions
      and not necessarily associated with depression may be more appropriate. Authors
      recommend further validity testing of the CSDD with similar populations of frail,
      institutionalized older adults.

PMID- 12213696
TI  - Comparison of adult and geriatric psychiatric practice patterns: findings from
      the American Psychiatric Association's Practice Research Network.
AB  - OBJECTIVE: The authors explored diagnostic and treatment patterns for patients
      under and over age 65 seen by a nationally representative sample of psychiatrists
      participating in the American Psychiatric Association's Practice Research
      Network. METHODS: Detailed patient information, including demographic and
      financial characteristics, diagnoses, service utilization, and treatment, was
      collected by 383 psychiatrists on 1,026 patients to assess the impact of patient
      age on pharmacotherapy and psychotherapy service use as well as treatment
      outcomes. RESULTS: Approximately 15% of the patient sample was over age 65.
      Compared with patients ages 19-64, a lower percentage of geriatric patients had
      Axis I comorbidity, but a higher percentage had Axis III comorbidity. Geriatric
      patients were more often treated in hospital settings, and older patients were
      less likely to have their visits adversely affected by financial pressures of the
      healthcare system. Over 60% of patients in both age-groups received
      antidepressants, but there was a disproportionately increased use of
      antipsychotics and antianxiety/benzodiazepine medications among geriatric
      patients. Being age 65+ was a strong predictor for "improved" clinician rating on
      general assessment scores, but failed to be a predictor of receiving
      psychotherapy or pharmacotherapy. CONCLUSION: There were important differences
      between subject groups. Overall, American psychiatrists treat a complex group of
      geriatric patients suffering from major mental disorders complicated by medical
      comorbidity. Additional studies would further enhance our understanding of the
      delivery of mental health services to elderly patients and improve training of
      psychiatrists who help care for our aging population.

PMID- 12213697
TI  - Genome survey for loci that influence successful aging: sample characterization,
      method validation, and initial results for the Y chromosome.
AB  - OBJECTIVE: A systematic genome survey was initiated to identify loci that affect
      the likelihood of reaching age 90 with preserved cognition. This communication
      describes the clinical characterization and comparison of the experimental
      groups, validation of the experimental method, and results for the Y chromosome.
      METHODS: The genome survey was conducted at 10 cM resolution for simple sequence
      tandem repeat polymorphisms (SSTRPs) that identify genes for successful aging by
      virtue of linkage disequilibrium. Efficiency was enhanced by genotyping pools of
      DNA from 100 cognitively intact elders (50 men/50 women) and 100 young (age 18-25
      years) adults matched for sex, race, ethnicity, and geographic location. RESULTS:
      Elders (94 nonagenarians, 6 centenarians) manifested preserved cognition, as
      reflected by clinical and psychometric assessments; "good" average capacity to
      carry out their activities of daily living; and the majority were living
      independently despite multiple medical conditions. None had a history of mental
      disorders in early or middle adulthood, only one was a current smoker, and 80%
      consumed alcohol less than once each month. The genome survey method detected the
      expected elevation of the APOE epsilon2 allele frequency, and reciprocal
      reduction in the epsilon4 frequency, among the elders, compared with the young
      adults. It also detected significant differences in the allelic distributions of
      DYS389 and DYS390, which are separated by only 2.6 Mb near the centromere of Yq.
      CONCLUSIONS: These results suggest that several behavioral and genetic factors
      may contribute to the likelihood of achieving exceptional longevity with
      preserved cognition.

PMID- 12213698
TI  - Greater depression severity associated with less improvement in depression
      associated cognitive deficits in older subjects.
AB  - OBJECTIVES: Elderly depressed patients often exhibit cognitive deficits, which
      may improve with drug therapy. The authors investigated the relationship of
      baseline depression severity and cognitive improvement with antidepressant
      treatment in depressed patients with mild cognitive impairment. METHODS: Mini
      Mental State Exam (MMSE) and Montgomery-Asberg Depression Rating Scale (MADRS)
      scores were measured in 52 depressed geriatric patients without dementia at
      baseline, 6, and 12 months, during an intent-to-treat period. A repeated-measures
      regression model tested the effect of MADRS score on MMSE. RESULTS: MMSE changes
      were significant and linear over time, with an average increase of 0.72 in the
      MMSE per 6-month interval. The final model showed that for every point increase
      in baseline MADRS, the average 6-month increase in MMSE decreased by 0.12.
      Repeated MADRS measurements did not significantly alter its predictive value.
      CONCLUSION: Greater baseline depression severity in older subjects with mild
      cognitive deficits is associated with less improvement in those deficits even
      with successful antidepressant therapy.

PMID- 12213700
TI  - Hyaluronan and tumor growth.

PMID- 12213701
TI  - Intravascular location of breast cancer cells after spontaneous metastasis to the
      lung.
AB  - In this study, we examined the hypothesis that early pulmonary metastases form
      within the vasculature. We introduced primary tumors in immunocompromised mice by
      subcutaneous injection of murine breast carcinoma cells (4T1) expressing green
      fluorescent protein. Isolated ventilated and perfused lungs from these mice were
      examined at various times after tumor formation by fluorescent microscopy. The
      vasculature was visualized by counterstaining with 1,1-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine (DiI)-acetylated low-density lipoprotein. These
      experiments showed that metastatic cells derived by spontaneous metastases were
      intravascular, and that early colony formation was intravascular. The location of
      the tumor cells was confirmed by deconvolution analysis. This work extends our
      previous study(1) that sarcoma cells injected intravenously form intravascular
      colonies to spontaneous metastasis and to a carcinoma model system. Many of the
      tumor cells seen were single implying that tumor cells may travel as single
      cells. These results support a model for pulmonary metastasis in mice in which 1)
      tumor cells can attach to lung endothelium soon after arrival; 2) surviving tumor
      cells proliferate intravascularly in this model; and 3) extravasation of the
      tumor occurs when intravascular micrometastatic foci outgrow the vessels they are
      in.

PMID- 12213702
TI  - The role of the thymus in development of necrotizing arteritis in transgenic rats
      carrying the env-pX gene of human T-cell leukemia virus type-I.
AB  - Necrotizing arteritis mimicking polyarteritis nodosa occurred in transgenic rats
      carrying the env-pX gene of human T-cell leukemia virus type I. To investigate
      the pathogenesis of necrotizing arteritis in these rats (env-pX rats), adoptive
      transfers of spleen cells and bone marrow cells were done from env-pX rats before
      they developed arteritis to nontransgenic rats. Necrotizing arteritis occurred in
      lethally irradiated nontransgenic rats reconstituted by env-pX spleen cells, thus
      indicating that the env-pX transgene in affected vessels may not be essential for
      the development of arteritis. In contrast, arteritis was not induced in
      nontransgenic recipients by adoptive transfers of env-pX bone marrow cells, which
      suggested that T cells derived from the env-pX thymus may play a role in the
      development of arteritis. To clarify if the process of differentiation of T cells
      in the env-pX thymus is crucial to develop necrotizing arteritis, reciprocal
      exchange of thymus frameworks was done between env-pX and nontransgenic rats.
      Necrotizing arteritis occurred in nontransgenic rats with an env-pX thymus
      framework, whereas development of arteritis was suppressed in env-pX rats in
      which the thymus framework was replaced with a nontransgenic one. This collective
      evidence shows that the thymus is directly associated with the development of
      necrotizing arteritis in env-pX rats.

PMID- 12213703
TI  - Novel expression of vascular cell adhesion molecule-1 (CD106) by squamous
      epithelium in experimental acute graft-versus-host disease.
AB  - Vascular cell adhesion molecule-1 (VCAM-1; CD106), the receptor for VLA-4, is an
      important mediator of adhesive and co-stimulatory interactions that govern
      cutaneous immune responses. Initial studies designed to elucidate temporal
      aspects of endothelial adhesion molecule induction in murine acute graft-versus
      host disease (aGVHD) revealed unexpected and novel VCAM-1 expression by cutaneous
      and mucosal epithelial cells. Immunohistochemical techniques confirmed VCAM-1
      staining as early as 7 days after transplantation in a distinctive subpopulation
      of squamous epithelial cells that normally occupy focal domains within the
      epidermal basal cell layer, the follicular infundibulum, and the dorsal lingual
      epithelium. Specifically, VCAM-1 expression was intimately associated with rete
      ridge-like prominences in footpad epidermis and in dorsal lingual epithelium.
      VCAM-1, as evaluated by serial section-labeling techniques, was preferentially
      expressed at sites of early epithelial infiltration by CD4(+) T cells. Western
      blot analysis confirmed expression of the 110-kd isoform of VCAM-1 in epithelium
      isolated from aGVHD animals, and immunoelectron microscopy demonstrated VCAM-1
      reactivity restricted exclusively to epithelial cell plasma membranes. It is
      concluded that VCAM-1 is selectively expressed by discrete squamous epithelial
      subpopulations in murine aGVHD. As such, VCAM-1 may play a previously
      unrecognized role in mediating interactions between donor effector T lymphocytes
      and host epithelial cell targets.

PMID- 12213704
TI  - Enteric expression of the integrin alpha(v)beta(6) is essential for nematode
      induced mucosal mast cell hyperplasia and expression of the granule chymase,
      mouse mast cell protease-1.
AB  - The immunoregulatory cytokine transforming growth factor (TGF)-beta(1) is
      secreted as a biologically inactive complex with latency-associated peptide,
      which must be modified by local factors to expose the functionally active
      cytokine. The epithelial integrin alpha(v)beta(6) mediates local activation of
      TGF-beta(1) in the lung and beta(6)(-/-) mice exhibit exaggerated pulmonary
      inflammation, but their response to inflammatory stimuli in the gut has not been
      investigated. We found that both beta(6) and TGF-beta(1) are constitutively
      expressed in the jejunal epithelial compartment in uninfected mice and during
      infection with the intestinal nematode Nippostrongylus brasiliensis. We also
      present data showing that beta(6)(-/-) mice are seriously compromised in their
      ability to mount a mucosal mast cell response after infection, and there is a
      significant reduction in the expression and systemic release of the granule
      chymase, mouse mast cell protease-1. Because in vitro expression of this chymase
      is regulated by TGF-beta(1), these data indicate that in the absence of
      alpha(v)beta(6) epithelially expressed TGF-beta(1) may not be activated, with a
      consequent absence of expression of mouse mast cell protease-1 and down
      regulation of the mucosal mast cell response.

PMID- 12213705
TI  - Functional tyrosine kinase inhibitor profiling: a generally applicable method
      points to a novel role of platelet-derived growth factor receptor-beta in
      tuberous sclerosis.
AB  - Tumors often exhibit activation of specific tyrosine kinases, which may allow
      targeting of therapy through inhibition of tyrosine kinase signaling. This
      strategy has been used successfully in the development of STI571 (gleevec), an
      inhibitor of bcr-abl tyrosine kinase that has been used successfully in the
      treatment of chronic myelogenous leukemia. STI571 also shows activity against c
      kit and platelet-derived growth factor receptor-beta (PDGFRbeta) tyrosine kinase
      signaling, thus potentially expanding the number of tumors that may respond to
      it. We describe a simple and rapid method to assess functional activity of
      tyrosine kinase signaling that is broadly applicable to tumor types. As proof of
      principle, we have applied it to cells that serve as models of the autosomal
      dominant tumor syndrome tuberous sclerosis (TS). We found that TS model cells
      derived from tuberin heterozygous mice and from a human renal angiomyolipoma are
      highly sensitive to PDGFR antagonists and that these cells express PDGFRbeta.
      Given that PDGFRbeta signaling is inhibited by STI571, we found that SV7tert
      human angiomyolipoma cells are sensitive to STI571. Thus, we describe a novel but
      simple method of determining the functional tyrosine kinase profile of a
      neoplastic cell and our results suggest that STI571 might be useful in the
      treatment of neoplasms commonly seen in patients with TS.

PMID- 12213706
TI  - Development of a frozen cell array as a high-throughput approach for cell-based
      analysis.
AB  - Recent advances in molecular biology, human genetics, and functional genomics
      tremendously increase the number of molecular targets available for potential
      therapeutic and diagnostic use. To complement DNA array data, cost-efficient high
      throughput technologies providing reliable information at the protein level need
      to be developed. Here we describe the generation of a frozen cell array that
      required the use of single cell suspensions and could serve various applications
      such as the analysis of specific antibody or ligand binding to a large panel of
      different cell types. As an example, binding of an anti-human epithelial cell
      adhesion molecule monoclonal antibody to 24 different cell lines has been
      analyzed using the cell array and compared to the data generated by fluorescence
      activated cell sorting. The reliability and flexibility of our frozen cell array
      technology is compatible with the needs of high-throughput screening for drug
      discovery and target validation.

PMID- 12213707
TI  - A new method for large scale isolation of kidney glomeruli from mice.
AB  - Here we report a new isolation method for mouse glomeruli. The method is fast and
      simple and allows for the isolation of virtually all glomeruli present in the
      adult mouse kidney with minimal contamination of nonglomerular cells. Mice were
      perfused through the heart with magnetic 4.5- micro m diameter Dynabeads. Kidneys
      were minced into small pieces, digested by collagenase, filtered, and collected
      using a magnet. The number of glomeruli retrieved from one adult mouse was 20,131
      +/- 4699 (mean +/- SD, n = 14) with a purity of 97.5 +/- 1.7%. The isolated
      glomeruli retained intact morphology, as confirmed by light and electron
      microscopy, as well as intact mRNA integrity, as confirmed by Northern blot
      analysis. The method was applicable also to newborn mice, which allows for the
      isolation of immature developmental stage glomeruli. This method makes feasible
      transcript profiling and proteomic analysis of the developing, healthy and
      diseased mouse glomerulus.

PMID- 12213709
TI  - Neuropathogenesis of lentiviral infection in macaques: roles of CXCR4 and CCR5
      viruses and interleukin-4 in enhancing monocyte chemoattractant protein-1
      production in macrophages.
AB  - Neurological disease associated with lentiviral infection occurs mainly as a
      consequence of primary replication of the virus or a combination of the virus
      infection and replication of opportunistic pathogens in the central nervous
      system. Recent studies have shown that whereas the disease can be caused by CCR5
      tropic viruses alone, its induction by CXCR4 (X4) tropic viruses occurred usually
      in association with infections caused by opportunistic pathogens and in the
      presence of a Th2 cytokine, interleukin (IL)-4.(1,2) Further, X4-mediated
      neurological disease developed preferentially in rhesus compared to pig-tailed
      macaques. Because macrophages are the target cells for lentiviral infection in
      the brain and because macrophage chemoattractant protein (MCP)-1 is one of the
      major chemokines that is closely associated with acquired immune deficiency
      syndrome (AIDS) dementia, we tested for correlations between MCP-1 production and
      virus tropism in macrophages from the two species of macaques. The studies showed
      that the higher susceptibility of rhesus macaques to X4 virus-mediated
      encephalitis correlated with heightened production of virus and MCP-1 in cultured
      macrophages from this species and that these effects were further enhanced with
      treatment with IL-4. However, the latter effect was restricted to macrophages
      infected with X4 viruses. IL-4 may therefore be a basic requirement for X4
      viruses to cause central nervous system disease.

PMID- 12213708
TI  - A novel, essential control for clonality analysis with human androgen receptor
      gene polymerase chain reaction.
AB  - The most widely used technique for determining clonality based on X-chromosome
      inactivation is the human androgen receptor gene polymerase chain reaction (PCR).
      The reliability of this assay depends critically on the digestion of DNA before
      PCR with the methylation-sensitive restriction enzyme HpaII. We have developed a
      novel method for quantitatively monitoring the HpaII digestion in individual
      samples. Using real-time quantitative PCR we measured the efficiency of HpaII
      digestion by measuring the amplification of a gene that escapes X-chromosome
      inactivation (XE169) before and after digestion. This method was tested in blood
      samples from 30 individuals: 2 healthy donors and 28 patients with
      myelodysplastic syndrome. We found a lack of XE169 DNA reduction after digestion
      in the granulocytes of two myelodysplastic syndrome patients leading to a false
      polyclonal X-chromosome inactivation pattern. In all other samples a significant
      reduction of XE169 DNA was observed after HpaII digestion. The median reduction
      was 220-fold, ranging from a 9.0-fold to a 57,000-fold reduction. Also paraffin
      embedded malignant tissue was investigated from two samples of patients with
      mantle cell lymphoma and two samples of patients with colon carcinoma. In three
      of these cases inefficient HpaII digestion led to inaccurate X-chromosome
      inactivation pattern ratios. We conclude that monitoring the efficiency of the
      HpaII digestion in a human androgen receptor gene PCR setting is both necessary
      and feasible.

PMID- 12213710
TI  - Regulation of angiogenesis by vascular endothelial growth factor and angiopoietin
      1 in the rat aorta model: distinct temporal patterns of intracellular signaling
      correlate with induction of angiogenic sprouting.
AB  - Vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) promote the
      spontaneous angiogenic response of freshly cut rat aortic rings. When VEGF and
      Ang-1 were tested in cultures of 14-day-old rings, which are quiescent and unable
      to spontaneously produce neovessels, only VEGF was capable of inducing an
      angiogenic response. Ang-1 failed to initiate angiogenesis in this system, but
      significantly potentiated VEGF-induced neovessel sprouting. Potential differences
      in cell signaling triggered by VEGF and Ang-1 were evaluated in cultures of
      quiescent rings. VEGF induced biphasic and prolonged (15 minutes and 4 to 24
      hours) phosphorylation of p44/42 MAPK and Akt, while the effect of Ang-1 was
      transient and monophasic (15 minutes). Both VEGF and Ang-1 induced rapid,
      monophasic (15 minutes) phosphorylation of p38 MAPK. When VEGF and Ang-1 were
      administered together, the second peak of VEGF-induced p44/42 MAPK
      phosphorylation was markedly reduced. The effect of the VEGF/Ang-1 combination on
      AKT phosphorylation was, instead, additive over time, and sustained over a 24
      hour period. The VEGF/Ang-1 combination caused an additive effect also on p38
      MAPK phosphorylation at 1 hour. Confocal microscopy of VEGF-, Ang-1, or VEGF/Ang
      1-stimulated aortic rings double stained at time points of maximal
      phosphorylation for cell markers and signal transduction proteins demonstrated
      phosphorylated p44/42 MAPK, p38 MAPK, and Akt predominantly in endothelial cells.
      Experiments with specific inhibitors demonstrated that p44/42 MAPK and Akt, but
      not p38 MAPK, are necessary for neovessel sprouting. These results identify
      p44/42 MAPK and Akt as critical intracellular mediators of angiogenesis, whose
      transient phosphorylation is, however, not sufficient for the initiation of this
      process. The observation that sustained phosphorylation of these signaling
      pathways, particularly of Akt, correlates with induction of angiogenesis suggests
      that the duration of phosphorylation signals influences critical cellular events
      required for the induction of angiogenic sprouting.

PMID- 12213711
TI  - The lack of thrombospondin-1 (TSP1) dictates the course of wound healing in
      double-TSP1/TSP2-null mice.
AB  - Thrombospondin (TSP) 1 and 2, share the same overall structure and interact with
      a number of the same cell-surface receptors. In an attempt to elucidate their
      biological roles more clearly, we generated double-TSP1/TSP2-null animals and
      compared their phenotype to those of TSP1- and TSP2-null mice. Double-null mice
      exhibited an apparent phenotype that primarily represented the sum of the
      abnormalities observed in the single-null mice. However, surprisingly, the wound
      healing response in double-null mice resembled that in TSP1-null animals and
      differed from that in TSP2-nulls. Thus, although the excisional wounds of TSP2
      null mice are characterized by increased neovascularization and heal at an
      accelerated rate, TSP1-null and double-null animals demonstrated delayed healing,
      as indicated by the prolonged persistence of inflammation and delayed scab loss.
      Immunohistochemical analysis showed that, similar to TSP1-null mice, the
      granulation tissue of double-null mice was not excessively vascularized.
      Furthermore as in TSP1-nulls, decreases in macrophage recruitment and in the
      levels of monocyte chemoattractant protein-1 indicated that the inflammatory
      phase of the wound-healing response was impaired in double-null mice. Our data
      demonstrate that the consequences of a lack of TSP1 predominate in the response
      of double-null mice, and dictate the course of wound healing. These findings
      reflect distinct temporal and spatial expressions of TSP1 and TSP2 in the healing
      wound.

PMID- 12213712
TI  - alpha-Methylacyl-CoA racemase: expression levels of this novel cancer biomarker
      depend on tumor differentiation.
AB  - alpha-Methylacyl-CoA racemase (AMACR) has previously been shown to be a highly
      sensitive marker for colorectal and clinically localized prostate cancer (PCa).
      However, AMACR expression was down-regulated at the transcript and protein level
      in hormone-refractory metastatic PCa, suggesting a hormone-dependent expression
      of AMACR. To further explore the hypothesis that AMACR is hormone regulated and
      plays a role in PCa progression AMACR protein expression was characterized in a
      broad range of PCa samples treated with variable amounts and lengths of exogenous
      anti-androgens. Analysis included standard slides and high-density tissue
      microarrays. AMACR protein expression was significantly increased in localized
      hormone-naive PCa as compared to benign (P < 0.001). Mean AMACR expression was
      lower in tissue samples from patients who had received neoadjuvant hormone
      treatment but still higher compared to hormone-refractory metastases. The hormone
      sensitive tumor cell line, LNCaP, demonstrated stronger AMACR expression by
      Western blot analysis than the poorly differentiated cell lines DU-145 and PC-3.
      AMACR protein expression in cells after exposure to anti-androgen treatment was
      unchanged, whereas prostate-specific antigen, known to be androgen-regulated,
      demonstrated decreased protein expression. Surprisingly, this data suggests that
      AMACR expression is not regulated by androgens. Examination of colorectal cancer,
      which is not hormone regulated, demonstrated high levels of AMACR expression in
      well to moderately differentiated tumors and weak expression in anaplastic
      colorectal cancers. Taken together, these data suggest that AMACR expression is
      not hormone-dependent but may in fact be a marker of tumor differentiation.

PMID- 12213713
TI  - Inhibition of prostate tumor cell hyaluronan synthesis impairs subcutaneous
      growth and vascularization in immunocompromised mice.
AB  - Hyaluronan (HA), a secreted glycosaminoglycan component of extracellular
      matrices, is critical for cellular proliferation and motility during development.
      However, elevated circulating and cell-associated levels correlate with various
      types of cancer, including prostate. We have previously shown that aggressive
      PC3M-LN4 prostate tumor cells synthesize excessive HA relative to less aggressive
      cells, and express correspondingly higher levels of the HA biosynthetic enzymes
      HAS2 and HAS3. Inhibition of these enzymes by stable transfection of PC3M-LN4
      cells with anti-sense HAS2 or HAS3 expression constructs diminishes HA synthesis
      and surface retention. In this report, we used these HA-deficient cell lines to
      examine the role of HA in tumorigenicity. Subcutaneous injection of SCID mice
      with hyaluronan synthase (HAS) antisense-transfected cells produced tumors
      threefold to fourfold smaller than control transfectants. Tumors from HAS
      antisense transfectants were histologically HA-deficient relative to controls. HA
      deficiency corresponded to threefold reduced cell numbers per tumor, but
      comparable numbers of apoptotic and proliferative cells. Percentages of apoptotic
      cells in cultured transfectants were identical to those of control cells, but
      antisense inhibition of HA synthesis effected slower growth rate of cells in
      culture. Quantification of blood vessel density within tumor sections revealed 70
      to 80% diminished vascularity of HAS antisense tumors. Collectively, the results
      suggest HAS overexpression by prostate tumor cells may facilitate their growth
      and proliferation in a complex environment by enhancing intrinsic cell growth
      rates and promoting angiogenesis. Furthermore, this is the first report of a role
      for inhibition of HA synthesis in reducing tumor growth kinetics.

PMID- 12213714
TI  - Correlation of DNA hypomethylation at pericentromeric heterochromatin regions of
      chromosomes 16 and 1 with histological features and chromosomal abnormalities of
      human breast carcinomas.
AB  - Changes in DNA methylation status are not only important for regulating gene
      expression but are also suggested to induce chromosome instability. To reveal the
      correlation of DNA methylation status in heterochromatin regions with tumor
      histology and with chromosome alterations, DNA methylation status was examined by
      Southern blot analysis, and numerical and structural chromosome alterations,
      including the formation of der(16)t(1;16)/der(1;16), were examined by
      fluorescence in situ hybridization at the two loci in the pericentromeric
      satellite 2 regions of chromosomes 16 and 1 in 39 human breast carcinomas. DNA
      hypomethylation at the D16Z3 and the D1Z1 loci was detected in 31% (12 of 39) and
      36% (12 of 33) of carcinomas, respectively, and mostly concurred. DNA
      hypomethylation was more frequent in the carcinoma group of more aggressive
      histological types or grade 3 than in the carcinoma of less aggressive
      histological types or grades 1 and 2, and tended to be more frequent in
      carcinomas with > or =4 copies of chromosomes 16 and/or 1 than in carcinomas with
      < or =3 copies of any of these chromosomes. The frequency of DNA hypomethylation
      at the D16Z3 and the D1Z1 loci was 45% (10 of 22) and 53% (9 of 17) in carcinomas
      without der(16)t(1;16)/der(1;16), formation, but only 12% (2 of 17) and 19% (3 of
      16) in carcinoma with der(16)t(1;16)/der(1;16), respectively (P = 0.036 and
      0.070). The 16q breakage was almost equally detected between carcinoma groups
      with and without the DNA hypomethylation. DNA hypomethylation in the satellite 2
      regions was suggested to be associated with the accumulation of a large number of
      numerical chromosome alterations and involved in the development of breast
      carcinomas of aggressive histological features. On the contrary, chromosome
      instability induced by mechanisms other than DNA hypomethylation in
      heterochromatin regions might cause the formation of der(16)t(1;16)/der(1;16) and
      less aggressive breast carcinomas.

PMID- 12213715
TI  - Susceptibility to human immunodeficiency virus-1 infection of human foreskin and
      cervical tissue grown in explant culture.
AB  - Numerous studies have indicated a protective effect of male circumcision against
      acquisition of human immunodeficiency virus (HIV)-1. We investigated mechanisms
      responsible for the possible increased HIV-1 susceptibility of human foreskin.
      Foreskins from eight pediatric and six adult patients with (n = 3) and without (n
      = 11) histories of sexually transmitted disease were evaluated. Six cervical
      biopsies from HIV-1-seronegative women were included as controls. CD4(+) T cells,
      macrophages, and Langerhans' cells (LCs) were quantified using image analysis.
      Cells expressing HIV-1 co-receptors CCR5 and CXCR4 were quantified using
      immunofluorescence and image analysis. Foreskin biopsies were infected ex vivo in
      organotypic culture with HIV-1. HIV-1 DNA copies in foreskin and cervical mucosal
      tissue were compared and the infected cell phenotype was determined. Foreskin
      mucosa contained higher mean proportions of CD4(+) T cells (22.4%), macrophages
      (2.4%), and LCs (11.5%) in adults than in children (4.9%, 0.3%, and 6.2%,
      respectively) or in cervical mucosa (6.2%, 1.4%, and 1.5%, respectively). The
      highest proportions of CD4(+) T cells and LCs occurred in patients with a history
      of infection. Foreskin immune cells expressed predominantly the CCR5 HIV-1 co
      receptor. Adult foreskin mucosa had greater susceptibility to infection with
      HIV(bal) than cervical mucosa or the external surface of foreskin tissue.
      Circumcision likely reduces risk of HIV-1 acquisition in men by decreasing HIV-1
      target cells.

PMID- 12213716
TI  - The nucleophosmin-anaplastic lymphoma kinase fusion protein induces c-Myc
      expression in pediatric anaplastic large cell lymphomas.
AB  - The majority of pediatric anaplastic large cell lymphomas (ALCLs) carry the
      t(2;5)(p23;q35) chromosomal translocation that juxtaposes the dimerization domain
      of nucleophosmin with anaplastic lymphoma kinase (ALK). The nucleophosmin-ALK
      fusion induces constitutive, ligand-independent activation of the ALK tyrosine
      kinase leading to aberrant activation of cellular signaling pathways. To study
      the early consequences of ectopic ALK activation, a GyrB-ALK fusion was
      constructed that allowed regulated dimerization with the addition of coumermycin.
      Expression of the fusion protein caused a coumermycin-dependent increase in
      cellular tyrosine phosphorylation and c-Myc immunoreactivity, which was
      paralleled by a rise in c-myc RNA. To assess the clinical relevance of this
      observation, c-Myc expression was determined in pediatric ALK-positive and 
      negative lymphomas. Co-expression of c-Myc and ALK was seen in tumor cells in 15
      of 15 (100%) ALK-positive ALCL samples, whereas no expression of either ALK or c
      Myc was seen in six of six cases of ALK-negative T-cell lymphoma. C-Myc may be a
      downstream target of ALK signaling and its expression a defining characteristic
      of ALK-positive ALCLs.

PMID- 12213717
TI  - Nonselenium glutathione peroxidase in human brain : elevated levels in
      Parkinson's disease and dementia with lewy bodies.
AB  - Nonselenium glutathione peroxidase (NSGP) is a new member of the antioxidant
      family. Using antibodies to recombinant NSGP we have examined the distribution of
      this enzyme in normal, Parkinson's disease (PD), and dementia with Lewy body
      disease (DLB) brains. We have also co-localized this enzyme with alpha-synuclein
      as a marker for Lewy bodies. In normal brains there was a very low level of NSGP
      staining in astrocytes. In PD and DLB there were increases in the number and
      staining intensity of NSGP-positive astrocytes in both gray and white matter.
      Cell counting of NSGP cells in PD and DLB frontal and cingulated cortices
      indicated there was 10 to 15 times more positive cells in gray matter and three
      times more positive cells in white matter than in control cortices. Some neurons
      were positive for both alpha-synuclein and NSGP in PD and DLB, and double
      staining indicated that NSGP neurons contained either diffuse cytoplasmic alpha
      synuclein deposits or Lewy bodies. In concentric Lewy bodies, alpha-synuclein
      staining was peripheral whereas NSGP staining was confined to the central core.
      Immunoprecipitation indicated there was direct interaction between alpha
      synuclein and NSGP. These results suggest oxidative stress conditions exist in PD
      and DLB and that certain cells have responded by up-regulating this novel
      antioxidant enzyme.

PMID- 12213718
TI  - Differentiation of muscle-derived cells into myofibroblasts in injured skeletal
      muscle.
AB  - Injured muscle can initiate regeneration promptly by activating myogenic cells
      that proliferate and differentiate into myotubes and myofibers. However, the
      recovery of the injured skeletal muscle often is hindered by the development of
      fibrosis. We hypothesized that the early-appearing myogenic cells in the injured
      area differentiate into myofibroblasts and eventually contribute to the
      development of fibrosis. To investigate this, we transplanted a genetically
      engineered clonal population of muscle-derived stem cells (MC13 cells) into the
      skeletal muscle of immunodeficient SCID mice, which were lacerated 4 weeks after
      transplantation. The MC13 cells regenerated numerous myofibers in the
      nonlacerated muscle and these myogenic cells were gradually replaced by
      myofibroblastic cells in the injured muscle. Our results suggest that the release
      of local environmental stimuli after muscle injury triggers the differentiation
      of myogenic cells (including MC13 cells) into fibrotic cells. These results
      demonstrate the potential of muscle-derived stem cells to differentiate into
      different lineages and illustrate the importance of controlling the local
      environment within the injured tissue to optimize tissue regeneration via the
      transplantation of stem cells.

PMID- 12213719
TI  - Therapeutic effect of angiostatin gene transfer in a murine model of
      endometriosis.
AB  - Endometriosis, the growth of ectopic endometrial tissue, is a chronic recurrent
      disease affecting 10% of the female population causing dyspareunia, pelvic pain,
      dysmenorrhea, and infertility. Suppression of ovarian activity is the cornerstone
      of medical therapy with limited benefit and severe adverse effects. Angiogenesis
      plays a major role in the development of endometriosis suggesting that anti
      angiogenic therapy would offer a new therapeutic approach. We report successful
      treatment of endometriosis in estrogen-supplemented ovariectomized mice by
      transient overexpression (6 to 10 days of duration) of the gene for a natural
      angiogenesis inhibitor angiostatin, delivered to the peritoneum by a replication
      deficient adenovirus vector (AdAngiostatin). Established endometriosis was
      eradicated in 14 of 14 AdAngiostatin-treated animals, whereas 11 of 13 control
      animals showed full disease development. Administered to normal cycling mice for
      the same transient period, AdAngiostatin caused impaired ovarian function with
      suppressed corpus luteum development, decreased production of estradiol and
      progesterone, decreased ovarian and uterine weight, and increased body weight.
      AdAngiostatin treatment lowered the levels of sex steroids but did not induce
      total castration. Gene therapy with angiogenic inhibitors is a highly effective
      treatment for endometriosis, even in a host with preserved estrogen levels.
      However, local or targeted delivery of the gene must be considered to avoid
      prolonged systemic effects and impaired ovarian function.

PMID- 12213720
TI  - Innate immune responses to cytomegalovirus infection in the developing mouse
      brain and their evasion by virus-infected neurons.
AB  - Cytomegalovirus (CMV) is the most frequent infectious cause of developmental
      brain disorders in humans. Here we show the role of innate immune responses
      caused by natural killer (NK) cells and nitric oxide (NO) derived from brain
      macrophages during murine CMV (MCMV) infection of the developing brain. Viral
      replication in the brain of newborn mice was significantly enhanced by
      administration of anti-asialo-GM1 antibody, specific for NK cells, or L-N6-(1
      imminoethyl)-lysine, a specific inhibitor of NO synthase 2 (NOS2). These results
      suggest that NK cells and NO contribute to the viral clearance from the brain. At
      3 days postinfection (dpi) MCMV early antigen (Ag)-positive cells were
      immunohistochemically detected in the periventricular area, where most of the
      positive cells were macrophages. At 7 dpi MCMV-Ag was found not only in cells of
      the periventricular area but also in neurons of the hippocampus and cortex. At 11
      dpi MCMV-Ag disappeared from the periventricular area, but persisted in neurons.
      In the periventricular area, NK cells and NOS2-positive macrophages were
      associated with MCMV-Ag-positive cells. In contrast, there were very few NK cells
      and NOS2-positive macrophages around the MCMV-Ag-positive neurons. In situ
      hybridization for MCMV DNA demonstrated that positive signals were found mostly
      in the periventricular cells, and rarely in neurons. These results suggest that
      the innate immune responses are restricted to the virus-replicating cells, and do
      not affect MCMV-infected neurons. Therefore, evasion of the innate immune
      responses by MCMV-infected neurons may be an important factor in supporting the
      viral persistence in the developing brain.

PMID- 12213721
TI  - Blockade of epidermal growth factor receptor signaling on tumor cells and tumor
      associated endothelial cells for therapy of human carcinomas.
AB  - The purpose of this study was to determine whether the expression of epidermal
      growth factor receptor (EGF-R) and activated EGF-R by tumor-associated
      endothelial cells is influenced by interaction with specific growth factors in
      the microenvironment. Different human carcinoma cell lines expressing EGF-R with
      low or high levels of EGF/transforming growth factor (TGF)-alpha were implanted
      into orthotopic organs of nude mice. In the EGF/TGF-alpha-positive bladder cancer
      (253J-BV), pancreatic cancer (L3.6pl), and renal cancer (RBM1-IT) but not in the
      EGF/TGF-alpha-negative renal cancer SN12-PM6, tumor-associated endothelial cells
      expressed EGF-R and activated EGF-R. Mice were implanted with human 253J-BV
      bladder tumors (EGF+) or human SN12-PM6 renal tumors (EGF-). Treatment with oral
      PKI 166 (a specific inhibitor of EGF-R phosphorylation) alone, intraperitoneal
      paclitaxel alone (253J-BV), gemcitabine alone (SN12-PM6), or combination of PKI
      166 and chemotherapy produced a 60%, 32%, or 81% reduction in the volume of 253J
      BV bladder tumors, respectively, and 26%, 23%, or 51% reduction in the volume of
      SN12-PM6 kidney tumors, respectively. Immunohistochemical analyses demonstrated
      down-regulation of activated EGF-R in EGF/TGF-alpha-positive and EGF/TGF-alpha
      negative lesions from mice treated with PKI 166, although apoptosis of tumor
      associated endothelial cells was found only in EGF/TGF-alpha-positive tumors.
      Collectively, these data suggest that expression of activated EGF-R by tumor
      associated endothelial cells provides an important target for therapy.

PMID- 12213722
TI  - Differential expression of cysteine and aspartic proteases during progression of
      atherosclerosis in apolipoprotein E-deficient mice.
AB  - Several groups of proteolytic enzymes are able to degrade components of the
      extracellular matrix. During atherosclerosis, matrix remodeling is believed to
      influence the migration and proliferation of cells within the plaque. In the
      present study, gene expression of several proteases and their inhibitors was
      analyzed during the development of atherosclerosis in apolipoprotein E-deficient
      (ApoE-/-) mice. Quantitative real-time polymerase chain reaction was used to
      study gene expression of proteases after 10 and 20 weeks in ApoE-/- and C57BL/6
      mice and in atherosclerotic lesions and nonaffected regions of the same ApoE-/-
      mouse. Some of the differentially expressed proteolytic enzymes were studied by
      immunohistochemistry. The matrix metalloproteinase (MMP)-9 and its inhibitor TIMP
      1 were differentially expressed and the expression increased with time. Urokinase
      type plasminogen activator showed no major expression. In contrast, cathepsins B,
      D, L, and S all showed strong and increased expression in ApoE-/- mice compared
      to C57BL/6 mice whereas the expression of their inhibitor, cystatin C, did not
      differ between the two mouse strains. The expression of cathepsins was mainly
      localized to the lesions and not to nonaffected regions of the aorta of ApoE-/-
      mice. Furthermore, cathepsin expression was similar to the expression of the
      macrophage marker macrosialin (CD68) although expression of cathepsins B, D, and
      L could be demonstrated in healthy C57BL/6 mice and in nonaffected vessel
      segments of atherosclerotic ApoE-/- mice. Cathepsin S mRNA expression was
      restricted to lesions of ApoE-/- mice. Furthermore, cathepsin S was the only
      cathepsin that was expressed in the media and absent in lipid-rich regions. All
      cathepsins studied showed intimal expression, the degree and localization of
      which differed between individual cathepsins. In conclusion, increased expression
      of several cathepsins in atherosclerotic lesions suggests that these proteases
      may participate in the remodeling of extracellular matrix associated with the
      atherosclerotic process.

PMID- 12213724
TI  - Genetic imbalances in progressed B-cell chronic lymphocytic leukemia and
      transformed large-cell lymphoma (Richter's syndrome).
AB  - Chromosomal imbalances were examined by comparative genomic hybridization in 30
      cases of B-cell chronic lymphocytic leukemia (CLL) at diagnosis, in sequential
      samples from 17 of these patients, and in 6 large B-cell lymphomas transformed
      from CLL [Richter's syndrome (RS)] with no available previous sample. The most
      common imbalances in CLL at diagnosis were gains in chromosome 12 (30%), and
      losses in chromosomes 13 (17%), 17p (17%), 8p (7%), 11q (7%), and 14q (7%). The
      analysis of sequential samples showed an increased number of chromosomal
      imbalances in 6 of 10 (60%) patients with clinical progression and in 2 patients
      with stable stage C disease. No karyotypic evolution was observed in four cases
      with stable stage A disease and in one RS clonally unrelated to the previous CLL.
      Gains of 2pter, and 7pter, and losses of 8p, 11q, and 17p were recurrent
      alterations associated with karyotype progression. RS showed a higher number of
      gains, losses, total alterations, and losses of 8p and chromosome 9 than CLL at
      diagnosis. 17p losses were associated with p53 gene mutations and with a
      significantly higher number of chromosomal imbalances than tumors with normal
      chromosome 17 profile. However, no relationship was observed between 9p deletions
      and p16(INK4a) gene alterations. Losses of 17p and an increased number of losses
      at diagnosis were significantly associated with a shorter survival. These
      findings indicate that CLL has frequent chromosomal imbalances, which may
      increase during the progression of the disease and transformation into large cell
      lymphoma. Genetic alterations detected by comparative genomic hybridization may
      also be of prognostic significance.

PMID- 12213723
TI  - Tumor-associated macrophages express lymphatic endothelial growth factors and are
      related to peritumoral lymphangiogenesis.
AB  - Formation of lymphatic metastasis is the initial step of generalized spreading of
      tumor cells and predicts poor clinical prognosis. Lymphatic vessels generally
      arise within the peritumoral stroma, although the lymphangiopoietic vascular
      endothelial growth factors (VEGF)-C and -D are produced by tumor cells. In a
      carefully selected collection of human cervical cancers (stage pT1b1) we
      demonstrate by quantitative immunohistochemistry and in situ hybridization that
      density of lymphatic microvessels is significantly increased in peritumoral
      stroma, and that a subset of stromal cells express large amounts of VEGF-C and
      VEGF-D. The density of cells producing these vascular growth factors correlates
      with peritumoral inflammatory stroma reaction, lymphatic microvessel density, and
      indirectly with peritumoral carcinomatous lymphangiosis and frequency of lymph
      node metastasis. The VEGF-C- and VEGF-D-producing stroma cells were identified in
      situ as a subset of activated tumor-associated macrophages (TAMs) by expression
      of a panel of macrophage-specific markers, including CD68, CD23, and CD14. These
      TAMs also expressed the VEGF-C- and VEGF-D-specific tyrosine kinase receptor
      VEGFR-3. As TAMs are derived from monocytes in the circulation, a search in
      peripheral blood for candidate precursors of VEGFR-3-expressing TAMs revealed a
      subfraction of CD14-positive, VEGFR-3-expressing monocytes, that, however, failed
      to express VEGF-C and VEGF-D. Only after in vitro incubation with tumor necrosis
      factor-alpha, lipopolysaccharide, or VEGF-D did these monocytes start to
      synthesize VEGF-C de novo. In conclusion VEGF-C-expressing TAMs play a novel role
      in peritumoral lymphangiogenesis and subsequent dissemination in human cancer.

PMID- 12213726
TI  - Abnormal uterine bleeding during progestin-only contraception may result from
      free radical-induced alterations in angiopoietin expression.
AB  - Abnormal uterine bleeding is the leading indication for discontinuation of long
      term progestin-only contraceptives (LTPOCs). Histological sections of endometria
      from LTPOC-treated patients display abnormally enlarged blood vessels at bleeding
      sites. Paradoxically, a trend toward reduced endometrial perfusion in LTPOC users
      has been reported in these patients. We hypothesized that hypoxia/reperfusion
      induced free radical production inhibits the expression of angiopoietin-1 (Ang
      1), a vessel stabilizing factor, leaving unopposed the effects of endothelial Ang
      2, a vessel-branching and permeability factor. Immunohistochemical studies
      confirmed selective decreases in stromal cell Ang-1 in LTPOC-exposed endometrium.
      To indirectly assess whether LTPOC enhances endometrial free radical production,
      immunostaining was conducted for the phosphorylated form of the stress-activated
      kinases SAPK/JNK and p38. These kinases were greatly increased in endometria from
      LTPOC-treated patients. Interestingly, the endothelial cells but not the stromal
      cells displayed enhanced immunostaining for the phosphorylated mitogen-activated
      kinase (pMAPK) after LTPOC treatment. To further examine the effects of
      progestin, hypoxia, and reactive oxygen species (ROS) on the regulation of Ang-1
      and Ang-2 as well as the activation of MAPK, SAPK/JNK, and p38 by the relevant
      cell types, we conducted in vitro studies with cultured human endometrial stromal
      cells (HESCs) and human endometrial endothelial cells (HEECs). Cultures of HESCs
      were treated with vehicle control, estradiol (E(2)), or with medroxyprogesterone
      acetate +/- E(2) under hypoxic and normoxic conditions. Although
      medroxyprogesterone acetate but not E(2) increased Ang-1 expression, hypoxia
      greatly decreased Ang-1 protein and mRNA expression. In contrast, HESCs did not
      appear to express Ang-2 protein or mRNA. Conversely, cultured HEECs did not
      appear to express Ang-1, but expressed Ang-2, the levels of which were
      significantly increased by hypoxia. Hypoxia also induced the phosphorylation of
      SAPK/JNK and p38 in both cultured HESCs and HEECs. Moreover, ROS such as that
      observed after hypoxia/reperfusion resulted in the activation of SAPK/JNK and p38
      in HESCs and HEECs and inhibited Ang-1 in cultured HESCs. These effects could be
      blocked by oxygen radical scavengers. Consistent with the in vivo studies, MAPK
      was activated after ROS treatment in HEECs but not in HESCs. Our findings suggest
      that LTPOC-induced endometrial bleeding occurs as a result of hypoxia/reperfusion
      induced free radicals that directly damage vessels and alter the balance of Ang-1
      and Ang-2 to produce the characteristic enlarged and permeable vessels that are
      prone to bleeding.

PMID- 12213725
TI  - Restricted SIV replication in rhesus macaque lung tissues during the acute phase
      of infection.
AB  - The extent to which simian immunodeficiency virus (SIV) replication in lung
      tissues contributes to the pool of viruses replicating during acute infection is
      incompletely understood. To address this issue, in situ hybridization was used to
      examine SIV replication in multiple lobes of lung from rhesus macaques infected
      with pathogenic SIV. Despite widespread viral replication in lymphoid and
      intestinal tissues, the lungs during acute infection harbored rare productively
      infected cells. Simultaneous immunohistochemical staining for the monocytic
      marker, CD68, revealed that SIV RNA(+) cells in lung tissues during acute
      infection were CD68(-), whereas during AIDS they were predominantly CD68(+) and
      localized in large foci in caudal lobes. SIV RNA(+) cells in spleen remained
      CD68(-) throughout disease. Since CD68 is also expressed by subpopulations of
      dendritic cells (DC), we also examined pulmonary CD68(+) cells for expression of
      additional DC markers. DC-LAMP mRNA was abundant in lung tissues and expressed
      predominantly by CD68(-) cells, whereas DC-SIGN mRNA was expressed in only very
      rare cells, indicating that SIV RNA(+) cells late in disease were most likely
      macrophages. These studies of SIV/host interactions demonstrate that macaque lung
      tissues are minimally infected during acute infection, exhibit changes in
      predominant target cells for infection, and express very little DC-SIGN.

PMID- 12213727
TI  - Hyperosmotic stress induces nuclear factor-kappaB activation and interleukin-8
      production in human intestinal epithelial cells.
AB  - Inflammatory bowel disease of the colon is associated with a high osmolarity of
      colonic contents. We hypothesized that this hyperosmolarity may contribute to
      colonic inflammation by stimulating the proinflammatory activity of intestinal
      epithelial cells (IECs). The human IEC lines HT-29 and Caco-2 were used to study
      the effect of hyperosmolarity on the IEC inflammatory response. Exposure of IECs
      to hyperosmolarity triggered expression of the proinflammatory chemokine
      interleukin (IL)-8 both at the secreted protein and mRNA levels. In addition,
      hyperosmotic stimulation induced the release of another chemokine, GRO-alpha.
      These effects were because of activation of the transcription factor, nuclear
      factor (NF)-kappaB, because hyperosmolarity stimulated both NF-kappaB DNA binding
      and NF-kappaB-dependent transcriptional activity. Hyperosmolarity activated both
      p38 and p42/44 mitogen-activated protein kinases, which effect contributed to
      hyperosmolarity-stimulated IL-8 production, because p38 and p42/44 inhibition
      prevented the hyperosmolarity-induced increase in IL-8 production. In addition,
      the proinflammatory effects of hyperosmolarity were, in a large part, mediated by
      activation of Na(+)/H(+) exchangers, because selective blockade of Na(+)/H(+)
      exchangers prevented the hyperosmolarity-induced IEC inflammatory response. In
      summary, hyperosmolarity stimulates IEC IL-8 production, which effect may
      contribute to the maintenance of inflammation in inflammatory bowel disease.

PMID- 12213728
TI  - Unique patterns of allelic imbalance distinguish type 1 from type 2 sporadic
      papillary renal cell carcinoma.
AB  - The molecular genetic correlates of a recently proposed subclassification of
      papillary renal cell carcinoma (PRCC) that designates tumors as type 1 and type 2
      based on histological features have not yet been established. Alterations of
      known genes in PRCC include missense mutations in the MET oncogene (7q31) and
      rare translocations fusing TFE3 at Xp11.2 with a variety of other loci. Previous
      cytogenetic and allelic loss studies of PRCC cases revealed gain of chromosome
      3q, 7, 8, 12q, 16, 17, and 20q, and loss of 1p, 6q, 9p, 11p, 13q, 14q, 18, 21q,
      X, and Y. We analyzed a series of sporadic type 1 and type 2 PRCC cases for MET
      mutations, TFE3 rearrangements, and allelic imbalance (AI) on 3p, 6, 7q, 9p, 11,
      13q, 14q, 17q, 18, 20q, and 21q and compared selected results with a series of
      conventional renal cell carcinomas. A somatic mutation M1149T was identified in
      MET exon 17 in 1 of 35 PRCC cases whereas TFE3 rearrangements were not detected
      in 22 PRCC cases examined. Significant differences in AI frequency between PRCCs
      and conventional renal cell carcinoma cases were seen on 3p (37.5% versus 77.8%,
      P = 0.01), 7q (42.9% versus 5.6%, P = 0.01), and 17q (54.5% versus 20.0%, P =
      0.03). Significant differences in AI frequency between type 1 and type 2 PRCCs
      were noted on 17q (78.6% versus 12.5%, P = 0.006) and 9p (0% versus 37.5%, P =
      0.02). Additional analyses suggested that the relationship between 17q AI and
      PRCC type may be independent of histological grade and stage. Our findings
      identify genetic differences between the recently proposed type 1 and type 2
      PRCCs, and support the premise that these subtypes arise from distinct genetic
      pathways.

PMID- 12213730
TI  - Aberrant CpG island methylation of multiple genes in intrahepatic
      cholangiocarcinoma.
AB  - Aberrant methylation of promoter CpG islands of human genes has been known as an
      alternative mechanism of gene inactivation and contributes to the carcinogenesis
      in many human tumors. We attempted to determine the methylation status of 18
      genes, or loci known to be frequently methylated in cancers of other organs, in
      79 resected intrahepatic cholangiocarcinomas and 15 normal bile duct epithelium
      by methylation-specific polymerase chain reaction and correlated the data with
      clinicopathological findings. Methylation frequencies of the loci tested in
      intrahepatic cholangiocarcinomas were 59.5% for 14-3-3sigma,26.6% for APC, 21.5%
      for E-cadherin, 17.7% for p16, 11.4% for MGMT, 11.4% for THBS1, 8.9% for p14,
      8.9% for TIMP3, 7.6% for DAP-kinase,6.3% for GSTP1, 5.1% for COX-2, 50.6% for
      MINT12, 40.5% for MINT1, 15.4% for MINT25, 35.4% for MINT32, and 1.3% for MINT31.
      Sixty-two (78.5%) of the 79 intrahepatic cholangiocarcinomas had methylation in
      at least one of these loci. Methylation was not detected in normal bile duct
      samples. There was a significant correlation between methylation and expressional
      decrease or loss of p16, E-cadherin, and GSTP1 proteins (P = 0.028, P = 0.044,
      and P < 0.001, respectively). The overall survival was poorer in the patients
      with CpG island methylation of APC, p16, and TIMP3 than in the patients without
      methylation (Kaplan-Meier log-rank test, P = 0.0128, 0.0447, and 0.0137,
      respectively). Age, gender, tumor stage, gross type, histological type, and
      differentiation had no correlation with methylation status of the specific gene.
      These results suggest that methylation is a frequent event in cholangiocarcinomas
      and contributes to the cholangiocarcinogenesis, and that CpG island methylation
      of APC, p16, or TIMP-3 may serve as a potential prognostic biomarker of the
      cholangiocarcinomas.

PMID- 12213729
TI  - Different incidence and pattern of p15INK4b and p16INK4a promoter region
      hypermethylation in Hodgkin's and CD30-Positive non-Hodgkin's lymphomas.
AB  - The p16INK4a and p15INK4b 5' CpG island hypermethylation has been described as
      one of the most frequent mechanisms leading to inactivation of these tumor
      suppressor genes in hematological malignancies. The p16 and p15 promoter regions
      were studied using methylation-specific polymerase chain reaction in 53 CD30 non
      Hodgkin's lymphomas (25 anaplastic large-cell, 13 peripheral T cell, and 15
      anaplastic diffuse large B cell) and 26 Hodgkin's lymphomas, with the aim of
      comparing the methylation status of these tumor suppressor genes in anaplastic
      large-cell lymphomas and other related entities. p16 and p15 methylation was
      detected, respectively, in 28% and 60% of CD30 non-Hodgkin's lymphomas and in 38%
      and 42% of Hodgkin's neoplasms. This confirms the p16-methylated status in
      Hodgkin's cases described in a single previous study and adds information
      concerning the p15 gene that was also found to be methylated in this lymphoma
      subtype. Methylation incidence within cases at diagnosis and at relapse suggests
      that it is an early event in anaplastic large-cell lymphomas, being involved in
      tumor progression in Hodgkin's cases. Our results show that although p16 and/or
      p15 methylation is involved in non-Hodgkin's and Hodgkin's tumors that share
      morphological and phenotypic features, differences in incidence, pattern of
      methylation, and implication in tumor progression are observed.

PMID- 12213732
TI  - Molecular genetic analysis of placental site trophoblastic tumors and epithelioid
      trophoblastic tumors confirms their trophoblastic origin.
AB  - Trophoblastic tumors represent a unique group of human neoplasms because they are
      derived from fetal tissue. Except for choriocarcinoma, the neoplasms that develop
      from human trophoblast are poorly characterized. Placental site trophoblastic
      tumors and epithelioid trophoblastic tumors are thought to arise from
      intermediate (extravillous) trophoblasts based on histopathological studies, but
      direct molecular evidence of a trophoblastic origin has not been established. In
      this study, we performed molecular analysis in an attempt to confirm their
      presumable trophoblastic origin. We demonstrated that such tumors contain a Y
      chromosomal locus and/or new (paternal) alleles not present in adjacent normal
      uterine tissue in all 31 informative cases. Loss of heterozygosity was found in
      60% of tumors and all 42 tumors assessed contained wild-type K-ras. All of the
      trophoblastic tumors were heterozygous in at least 1 of 10 single-nucleotide
      polymorphism markers studied in contrast to homozygosity in all 10 single
      nucleotide polymorphism markers in most complete hydatidiform moles indicating
      that these tumors are not related to complete hydatidiform moles. This study
      provides the first molecular evidence that placental site trophoblastic tumors
      and epithelioid trophoblastic tumors are of fetal (trophoblastic) origin.

PMID- 12213731
TI  - Expression of alpha7beta1 integrin splicing variants during skeletal muscle
      regeneration.
AB  - Integrin alpha7beta1 is a laminin receptor, both subunits of which have
      alternatively spliced, developmentally regulated variants. In skeletal muscle
      beta1 has two major splice variants of the intracellular domain (beta1A and
      beta1D). alpha7X1 and alpha7X2 represent variants of the alpha7 ectodomain,
      whereas alpha7A and alpha7B are variants of the intracellular domain. Previously
      we showed that during early regeneration after transection injury of muscle
      alpha7 integrin mediates dynamic adhesion of myofibers along their lateral
      aspects to the extracellular matrix. Stable attachment of myofibers to the
      extracellular matrix occurs during the third week after injury, when new
      myotendinous junctions develop at the ends of the regenerating myofibers. Now we
      have analyzed the relative expression of beta1A/beta1D and alpha7A/alpha7B and
      alpha7X1/alpha7X2 isoforms during regeneration for 2 to 56 days after transection
      of rat soleus muscle using reverse transcriptase-polymerase chain reaction and
      immunohistochemistry. During early regeneration beta1A was the predominant
      isoform in both the muscle and scar tissue. Expression of muscle-specific beta1D
      was detected in regenerating myofibers from day 4 onwards, ie, when myogenic
      mitotic activity began to decrease, and it became more abundant with the
      progression of regeneration. alpha7B isoform predominated on day 2. Thereafter,
      the relative expression of alpha7A transcripts increased until day 7 with the
      concomitant appearance of alpha7A immunoreactivity on regenerating myofibers.
      Finally, alpha7B again became the predominant variant in highly regenerated
      myofibers. Similarly as in the controls, alpha7X1 and alpha7X2 isoforms were both
      expressed throughout the regeneration with a peak in alpha7X1 expression on day 4
      coinciding with the dynamic adhesion stage. The results suggest that during
      regeneration of skeletal muscle the splicing of beta1 and alpha7 integrin
      subunits is regulated according to functional requirements. alpha7A and alpha7X1
      appear to have a specific role during the dynamic phase of adhesion, whereas
      alpha7B, alpha7X2, and beta1D predominate during stable adhesion.

PMID- 12213733
TI  - Independent regulation of transforming growth factor-beta1 transcription and
      translation by glucose and platelet-derived growth factor.
AB  - Proximal tubular renal epithelial cells may contribute to the pathogenesis of
      renal interstitial fibrosis in diabetes by generation of cytokines such as
      transforming growth factor (TGF)-beta1. We have previously demonstrated that
      proximal tubular renal epithelial cell TGF-beta1 synthesis may be modulated by
      elevated glucose concentration and by cytokines such as platelet-derived growth
      factor (PDGF). The aim of the current study was to characterize the mechanism by
      which glucose and PDGF synergistically stimulate the generation of TGF-beta1.
      Addition of either 25 mmol/L of D-glucose or low-dose PDGF increased TGF-beta1
      mRNA expression without stimulation of TGF-beta1 protein synthesis. In contrast
      sequential stimulation with 25 mmol/L of D-glucose for 48 hours followed by low
      dose (25 ng/ml) PDGF led to a significant increase in TGF-beta1 synthesis.
      Elevated glucose concentration stimulated de novo gene transcription as assessed
      by stimulation of a TGF-beta1 promoter-luciferase construct. This led to
      induction of a poorly translated TGF-beta1 transcript determined by polysome
      analysis. PDGF at low dose did not influence TGF-beta1 transcription, but led to
      alteration in TGF-beta1 mRNA stability and translation. Without a previous
      glucose-induced increase in the amount of TGF-beta1 transcript, PDGF did not
      stimulate significant TGF-beta1 protein synthesis. At a high dose (100 ng/ml)
      PDGF stimulated TGF-beta1 synthesis independent of glucose concentration. This
      was associated with increased TGF-beta1 gene transcription and alteration in TGF
      beta1 mRNA translational efficiency. In conclusion the data suggests that in
      diabetic nephropathy, the role of glucose is to lower the threshold at which a
      stimulus such as PDGF stimulates TGF-beta1 protein synthesis. The data also
      suggest that independent regulation of TGF-beta1 transcription and translation by
      glucose and PDGF account for their synergistic effect on TGF-beta1 protein
      synthesis. We hypothesize that the role of glucose in diabetic nephropathy is to
      prime the kidney for an injurious response to other stimuli.

PMID- 12213734
TI  - Multiple head and neck tumors frequently originate from a single preneoplastic
      lesion.
AB  - The development of second primary tumors has a negative impact on the prognosis
      of head and neck squamous cell carcinoma. Previously, we detected genetically
      altered and tumor-related mucosal lesions in the resection margins in 25% of
      unselected head and neck squamous cell carcinoma patients (Tabor MP, Brakenhoff
      RH, van Houten VMM, Kummer JA, Snel MHJ, Snijders PJF, Snow GB, Leemans CR,
      Braakhuis BJM: Persistence of genetically altered fields in head and neck cancer
      patients: biological and clinical implications. Clin Cancer Res 2001, 7: 1523
      1532). The aim of this study was to determine whether first and second primary
      tumors are clonally related and originate from a single genetically altered
      field. From 10 patients we analyzed the first tumor of the oral cavity or
      oropharynx, the >3-cm remote second primary tumor, and the mucosa from the tumor
      free margins from both resection specimens. We compared TP53 mutations and loss
      of heterozygosity profiles using 19 microsatellite markers at chromosomes 3p, 9p,
      13q, and 17p. In all patients, genetically altered mucosal lesions were detected
      in at least one resection margin from both first and second primary tumor.
      Evidence for a common clonal origin of the first tumor, second primary tumor, and
      the intervening mucosa was found for at least 6 of 10 patients. Our results
      indicate that a proportion of multiple primary tumors have developed within a
      single preneoplastic field. Based on different etiology and clinical
      consequences, we propose that independent second primary tumors should be
      distinguished from second field tumors, that arise from the same genetically
      altered field the first tumor has developed from.

PMID- 12213735
TI  - Reproductive pathology and sperm physiology in acid sphingomyelinase-deficient
      mice.
AB  - Types A and B Niemann-Pick disease (NPD) are lysosomal storage disorders
      resulting from the deficient activity of acid sphingomyelinase (ASM). In this
      manuscript we report the pathobiology of male gonadal tissue and sperm in a
      knockout mouse model of NPD and demonstrate the importance of ASM for normal
      sperm maturation and function. Characteristic lipid-filled vacuoles were evident
      in light micrographs of testis' seminiferous tubules and epithelial cells lining
      the epididymis of -/- mice. Electron micrographs extended these findings and
      revealed storage vesicles within Sertoli cells of the seminiferous tubules.
      Mature spermatozoa from -/- mice showed marked ASM deficiency and elevated levels
      of sphingomyelin and cholesterol. Flow cytometric analysis revealed that affected
      spermatozoa had disrupted plasma and acrosome membranes, and mitochondrial
      membrane depolarization. They also did not undergo proper capacitation.
      Morphological abnormalities such as kinks and bends at the midpiece-principle
      piece junction were evident in spermatozoa from affected mice, with consequent
      deficits in motility. Notably, the mutant sperm regained normal morphology on
      incubation in mild detergent, demonstrating that the bending defects were a
      direct consequence of membrane lipid accumulation. A mechanism for these
      abnormalities is proposed that suggests lipid accumulation in the gonads results
      in regulatory volume decrease defects within the developing sperm, and that
      regulatory volume decrease defects, in turn, lead to the observed abnormalities
      in sperm morphology and function. These results provide in vivo evidence that ASM
      activity plays a critical role in sperm maturation and function, and a basis for
      similar studies in sexually mature, male NPD patients.

PMID- 12213736
TI  - Deletion of decay-accelerating factor (CD55) exacerbates autoimmune disease
      development in MRL/lpr mice.
AB  - Decay-accelerating factor (DAF, CD55) is a glycosylphosphatidylinositol-anchored
      membrane protein that restricts complement activation on autologous cells. It is
      also a ligand for CD97, an activation-associated lymphocyte antigen with seven
      transmembrane domains. It is widely expressed on cells of both the hematopoietic
      and nonhematopoietic lineages. Although deficiency of DAF on human erythrocytes
      is associated with the hemolytic anemia syndrome paroxysmal nocturnal
      hemoglobinuria, the in vivo biology of DAF is still poorly understood. We
      addressed the in vivo function of DAF in a knockout mouse model and describe here
      that deletion of DAF exacerbates autoimmune disease development in MRL/lpr mice,
      a model for human systemic lupus erythematosus. Compared to DAF-sufficient
      littermate controls, DAF-deficient female MRL/lpr mice developed exacerbated
      lymphadenopathy and splenomegaly, higher serum anti-chromatin autoantibody
      levels, and aggravated dermatitis. Consistent with the phenotype of aggravated
      dermatitis in DAF-deficient mice, Northern and Western blots and
      immunofluorescence studies showed DAF to be expressed abundantly in the mouse
      skin, suggesting that it may play a particularly important role in this tissue.
      Histology and immunostaining demonstrated inflammatory infiltrate and focal C3
      deposition in early skin lesions, mostly along the dermal-epidermal junction.
      These results reveal a protective function of DAF in the development of a
      systemic autoimmune syndrome and suggest that dysfunction or down-regulation of
      DAF may contribute to autoimmune disease pathogenesis and manifestation.

PMID- 12213738
TI  - The next step forward.

PMID- 12213737
TI  - Pathway pathology: histological differences between ErbB/Ras and Wnt pathway
      transgenic mammary tumors.
AB  - To study phenotype-genotype correlations, ErbB/Ras pathway tumors (transgenic for
      ErbB2, c-Neu, mutants of c-Neu, polyomavirus middle T antigene (PyV-mT), Ras, and
      bi-transgenic for ErbB2/Neu with ErbB3 and with progesterone receptor) from four
      different institutions were histopathologically compared with Wnt pathway tumors
      [transgenes Wnt1, Wnt10b, dominant-negative glycogen synthase kinase 3-beta, beta
      Catenin, and spontaneous mutants of adenomatous polyposis coli gene (Apc)].
      ErbB/Ras pathway tumors tend to form solid nodules consisting of poorly
      differentiated cells with abundant cytoplasm. ErbB/Ras pathway tumors also have
      scanty stroma and lack myoepithelial or squamous differentiation. In contrast,
      Wnt pathway tumors exhibit myoepithelial, acinar, or glandular differentiation,
      and, frequently, combinations of these. Squamous metaplasia is frequent and may
      include transdifferentiation to epidermal and pilar structures. Most Wnt pathway
      tumors form caricatures of elongated, branched ductules, and have well-developed
      stroma, inflammatory infiltrates, and pushing margins. Tumors transgenic for
      interacting genes such as protein kinase CK2alpha (casein kinase IIalpha), and
      the fibroblast growth factors (Fgf) Int2/Fgf3 or keratinocyte growth factor
      (Kgf/Fgf7) also have the Wnt pathway phenotype. Because the tumors from the
      ErbB/Ras and the Wnt pathway are so distinct and can be readily identified using
      routine hematoxylin and eosin sections, we suggest that pathway pathology is
      applicable in both basic and clinical cancer research.

PMID- 12213740
TI  - Off-pump coronary artery surgery in the elderly.
AB  - We compared the results of off-pump (n = 186) and on-pump (n = 389) coronary
      artery bypass grafting in elderly patients over 70 years old. Patients undergoing
      single-vessel revascularization were excluded from the study. The 2 groups
      matched in preoperative risk factors. Operative mortality was comparable (off
      pump 2.2% versus on-pump 4.6%). The off-pump group fared better in intubation
      time (16 +/- 4 hours versus 25 +/- 5 hours), blood loss (365 +/- 58 mL versus 584
      +/- 72 mL), the need for blood transfusion (31.7% versus 44%), reoperation for
      bleeding (0.5% versus 3.6%), atrial fibrillation (10.2% versus 18.5%), intensive
      care unit stay (21 +/- 8 hours versus 34 +/- 10 hours), and total hospital stay
      (5 +/- 2 days versus 8 +/- 3 days). Off-pump bypass surgery is thus safe for
      elderly patients and is associated with reduced morbidity and shorter
      hospitalization than on-pump surgery.

PMID- 12213739
TI  - Surgical steps toward complete revascularization in off-pump coronary bypass.
AB  - Surgical techniques aimed at complete myocardial revascularization without the
      use of cardiopulmonary bypass are described. Between January 1998 and June 2000,
      coronary artery bypass was performed in 3,003 patients; an off-pump technique was
      used in 676 and cardiopulmonary bypass was employed in 2,327. Patient
      characteristics, demography, and preoperative risk factors of the two groups were
      compared retrospectively, and differences in operative variables and
      postoperative outcomes were analyzed. Using a commercially available suction
      stabilization device and the surgical and anesthetic techniques described herein,
      off-pump coronary revascularization was accomplished with results comparable to
      the on-pump approach.

PMID- 12213741
TI  - Coronary artery bypass in patients with severe left ventricular dysfunction.
AB  - We retrospectively reviewed the case records of 82 patients with severe left
      ventricular dysfunction (ejection fraction < 30%) who underwent coronary artery
      bypass grafting between March 1993 and February 2000. They were aged 28 to 76
      years (mean, 60 years), and 66 of them were male. Significant comorbid factors
      included hypertension (93%), diabetes mellitus (85%), and hypercholesterolemia
      (49%). The number of grafts used ranged from 1 to 3. The majority of the patients
      (91%) belonged to the Canadian Cardiovascular Society angina class III. Coronary
      angiography revealed single-vessel (in 16% of the patients), double-vessel (52%),
      and triple-vessel disease (32%), and left main stem disease (18%). Seven patients
      (9%) died within 48 hours after surgery. The mean duration of hospital stay was 7
      +/- 2 days. The 75 patients who survived were followed up for 3 months to 7
      years. At the 1-year follow-up, 61 of the 68 patients (90%) who were alive moved
      up from angina class III to class I. Our observations suggest that coronary
      bypass carries an acceptable mortality risk and may offer a better quality of
      life in patients with poor ventricular function.

PMID- 12213742
TI  - Redo mitral valve surgery using the port-access system.
AB  - Redo mitral valve surgery is hazardous, hence we explored an alternative approach
      using a port-access system that avoids reentry. Between October 1997 and December
      2000, 32 patients underwent mitral reoperation using the system. All patients had
      previous cardiac operations. This procedure consisted of a right anterolateral
      minithoracotomy and femorofemoral cannulation using special port-access
      instruments and endoaortic clamping in 24 patients or direct transthoracic
      sliding-rod aortic clamping in 8. The valve disease was of rheumatic etiology in
      28 patients and degenerative in 4. The valve was replaced in 31 cases and a
      paravalvular leak after mitral valve replacement was closed in 1. In 2 cases, the
      tricuspid valve was repaired along with mitral valve replacement. Mean total
      operating time was 4.5 +/- 1.2 hours, cardiopulmonary bypass time 162 +/- 72
      minutes, and aortic crossclamp time 62 +/- 21 minutes. There was no mortality,
      and mean stay in the intensive care unit was 22 +/- 7 hours and hospital stay 6.4
      +/- 1.2 days. Postoperative blood transfusion was required in 12 patients. In
      view of the favorable results, we recommend using the port-access system as a
      standard approach for mitral reoperation.

PMID- 12213743
TI  - Effects of intravenous triiodothyronine during coronary artery bypass surgery.
AB  - A prospective randomized and double-blind study was performed to evaluate whether
      perioperative triiodothyronine administration has any effect on cardiovascular
      performance after coronary artery bypass surgery. Sixty patients were assigned to
      2 groups of 30 each. When crossclamping ended, group A received an intravenous
      bolus of triiodothyronine, followed by infusion for 6 hours. Group B received a
      placebo. Serum triiodothyronine levels and hemo-dynamic parameters were serially
      measured. Mean postoperative cardiac index was slightly, but not significantly,
      higher in group A, whereas systemic vascular resistance was significantly lower
      in group A. Compared with preoperative values, serum triiodothyronine levels
      dropped significantly in group B at the end of cardiopulmonary bypass and
      remained low 12 hours postoperatively, while levels rose significantly in group
      A. No significant differences were detected between the groups in the incidence
      of arrhythmia, the need for inotropic support, intensive care unit stay,
      mortality, and morbidity. Perioperative administration of triiodothyronine
      increased cardiac output slightly and decreased systemic vascular resistance, but
      it had no effect on operative outcome. Routine use after coronary surgery is thus
      not recommended.

PMID- 12213744
TI  - Cerebral metabolism of nitric oxide during retrograde cerebral perfusion.
AB  - The aim of this study was to determine whether alpha- or pH-stat protects the
      brain during deep hypothermic retrograde cerebral perfusion. Fifteen anesthetized
      dogs on cardiopulmonary bypass were cooled to 18 degrees C under alpha-stat and
      underwent retrograde cerebral perfusion for 90 minutes under alpha-stat or pH
      stat, or underwent antegrade cardiopulmonary bypass under alpha-stat as the
      control. Cerebral blood flow of the cortex was monitored and serial analyses of
      blood gases and total nitric oxide oxidation products made. Cerebral blood flow
      and cerebral metabolic rate for oxygen were significantly higher and plasma
      levels of nitric oxide oxidation products in the outflow from the brain were
      significantly lower in retrograde cerebral perfusion under pH-stat than under
      alpha-stat. This study shows that reduced levels of nitric oxide oxidation
      products may protect against neuronal damage induced by nitric oxide and that
      increased cerebral blood flow under pH-stat may lead to a reduction of nitric
      oxide oxidation products. Under retrograde cerebral perfusion, pH-stat is thus
      better than alpha-stat for protecting the brain.

PMID- 12213745
TI  - Video-assisted thoracoscopic surgery for congenital heart disease.
AB  - We report our experience with video-assisted thoracoscopy in the surgical closure
      of heart septal defects. Nine patients, aged 10 to 26 years, underwent operation
      for closure of an atrial septal defect; and 3, aged 10 to 22 years, for closure
      of a ventricular septal defect. Three minithoracotomies with a diameter of 2 to 3
      cm were made in the fourth intercostal space of the right parasternum and the
      fourth and seventh intercostal spaces of the right middle axillary line,
      respectively. Through the openings and guided by a thoracoscope, a catheter was
      inserted into the superior vena cava, femorofemoral extracorporeal circulation
      was built, the aorta was crossclamped, and the myocardium was protected by cold
      cardioplegia. The right atrium was opened, and the defect was exposed with a
      traction suture. Primary closure of defects was performed successfully in all
      patients. The duration of aortic crossclamping and extracorporeal circulation
      ranged from 11 to 56 minutes and from 50 to 168 minutes, respectively.
      Postoperatively, cardiac murmur disappeared and echocardiograms showed no
      residual shunt. Repair of heart septal defects can be completely done with the
      assistance of video-assisted thoracoscopy, offering a new option with minimal
      incision.

PMID- 12213746
TI  - Outcome following repair of sinus venosus atrial septal defects in children.
AB  - The outcome of surgical repair of sinus venosus atrial septal defect was reviewed
      retrospectively. The operation was performed on 44 children aged 8 to 163 months,
      between April 1985 and November 1998. Median cardiopulmonary bypass and aortic
      crossclamp times were 58 minutes (range, 29 to 141 minutes) and 29 minutes
      (range, 4 to 67 minutes), respectively. Use of blood products decreased from 4.5
      units per patient in the first period (1985 to 1989) to 0.6 units in the last
      period (1995 to 1998). Median intensive care and hospital stays were 2 days
      (range, 1 to 12 days) and 6 days (range, 4 to 16 days), respectively. There was 1
      early death (2.3%). Complications included reexploration for bleeding in 2
      patients (4.5%) and for superior vena cava obstruction in 1 (2.3%), and
      arrhythmias in 3 (6.8%), which required a pacemaker in one. During follow-up of
      15 to 176 months, 83.8% of patients were in sinus rhythm. One required
      angioplasty for superior vena cava stenosis, hemodynamically insignificant
      residual shunt was found in 3, and mild superior vena cava stenosis in 3. Repair
      of sinus venosus atrial septal defect carries a low mortality and morbidity, but
      long-term follow-up is needed to monitor potential sinus node dysfunction and
      superior vena cava stenosis.

PMID- 12213747
TI  - Two-stage arterial switch operation: is late ever too late?
AB  - Results of the two-stage arterial switch operation in 49 patients with
      transposition of the great arteries, performed between January 1995 and September
      2000, were reviewed retrospectively. Twenty-one patients had a ventricular septal
      defect. Anatomical correction was carried out 21.89 +/- 9.86 months after
      pulmonary artery banding, with or without a modified Blalock-Taussig shunt.
      Hospital mortality was 8% (4 patients). During follow-up of 30.12 +/- 14.38
      months, there was 1 late death and 1 patient required reoperation for
      pseudoaneurysm of the ascending aorta. Actuarial survival and freedom from
      reoperation at 5 years were 90% and 97%, respectively. Late anatomic correction
      (> 6 months) after the preliminary procedure can be performed with an acceptable
      mortality and morbidity, but undue delay may lead to left ventricular
      dysfunction, arrhythmias, and new aortic valve regurgitation or subaortic
      stenosis.

PMID- 12213748
TI  - Limited right posterior thoracotomy approach to atrial septal defect.
AB  - Experience of atrial septal defect closure via a limited posterior thoracotomy is
      described. From July 1999 to May 2001, 75 prepubertal girls with a median age of
      7 years (range, 3 to 13 years) and a median weight of 18 kg (range, 10 to 46 kg)
      underwent atrial septal defect closure through a limited right posterior
      thoracotomy. All but 2 patients had an uneventful postoperative recovery. The
      median duration of ventilation was 13.3 hours (range, 4 to 24 hours). Median
      hospital stay was 6 days (range, 6 to 8 days). All patients were followed up for
      7 to 32 months (mean, 15 months). The wounds healed well without any restriction
      of limb movement. The limited posterior thoracotomy gave excellent cosmetic
      results and can be used as a safe alternative approach for atrial septal defect
      closure in prepubertal females.

PMID- 12213749
TI  - Evaluation of Tc-99m tetrofosmin scan for coronary artery disease diagnosis.
AB  - Detection of myocardial perfusion abnormalities using Tc-99m tetrofosmin was
      evaluated for sensitivity and specificity compared to coronary angiography.
      Between January 1996 and January 1998, exercise stress tests and myocardial
      scintigraphy were performed in 58 patients, followed by coronary angiography
      within 2 months. There were 48 males and 10 females, aged 33 to 72 years (mean,
      57 years). The sensitivity and specificity of exercise stress tests were 64% and
      68%, respectively, while the sensitivity and specificity of Tc-99m tetrofosmin
      scans were 88% and 75%, respectively, compared to angiography. For Tc-99m
      tetrofosmin scans, the sensitivity was 78% for the left anterior descending
      artery, 66% for the left circumflex artery, and 76% for the right coronary
      artery; specificity was 74% for the left anterior descending artery, 90% for the
      left circumflex artery, and 75% for the right coronary artery. It was concluded
      that Tc-99m tetrofosmin allowed high-quality myocardial perfusion imaging with
      results comparable to those obtained using thallium-201 chloride.

PMID- 12213750
TI  - Patch enlargement of the posterior mitral leaflet in ischemic regurgitation.
AB  - We discuss our early experience in 2 patients with a patch enlargement technique
      for treating chronic ischemic mitral regurgitation due to restricted motion of
      the posterior mitral leaflet. This technique corrects the restricted motion and
      offers better coaptation without compromising the mitral orifice.

PMID- 12213751
TI  - Septic pulmonary emboli caused by a hemodialysis catheter.
AB  - We present an unusual complication caused by a dialysis catheter inserted through
      the internal jugular vein into the central venous system. The 49-year-old male
      patient developed a right atrial thrombus, which became infected with
      Staphylococcus aureus, resulting in septic pulmonary embolism and septicemic
      shock. The thrombus was excised on cardiopulmonary bypass. The patient made an
      uneventful recovery.

PMID- 12213752
TI  - Limb ischemia due to use of internal thoracic artery in coronary bypass.
AB  - Immediately after undergoing coronary bypass grafting using the left internal
      thoracic artery, a 59-year-old man developed left leg ischemia. Right-to-left
      femoral artery crossover bypass was performed and the ischemia resolved. A 72
      year-old man developed left calf pain 12 days after a similar procedure;
      peripheral angiography revealed stenosis of the abdominal aorta and distal
      peripheral arteries, which did not require intervention.

PMID- 12213753
TI  - Postinfarction left ventricular free wall rupture repaired successfully.
AB  - Left ventricular free wall rupture is a well-recognized complication of
      myocardial infarction and a frequent cause of death. A 49-year-old man was
      successfully treated for a left ventricular free wall rupture that occurred on
      the third day after an anterior myocardial infarction. Concomitant myocardial
      revascularization was performed.

PMID- 12213754
TI  - Vascular echinococcosis.
AB  - Three patients with arterial echinococcosis presented with chronic or acute
      arterial occlusion. One case diagnosed as Leriche's syndrome was found at surgery
      to have aortic occlusion caused by hydatid cysts; arterial reconstruction was
      performed by aortoiliac interposition of a woven Dacron vascular graft. In the
      other 2 cases presenting with acute femoral or brachial artery occlusion,
      embolectomy revealed hydatid cysts as the cause of occlusion.

PMID- 12213755
TI  - Congenital cleft of anterior tricuspid leaflet in adolescent.
AB  - The diagnostic findings and treatment of an isolated congenital cleft of the
      anterior leaflet of the tricuspid valve in a 14-year-old boy are described. An
      atrial septal defect was closed by primary suturing, and the tricuspid valve was
      successfully reconstructed by De Vega annuloplasty.

PMID- 12213756
TI  - Cardiomyoplasty: first clinical case with new cardiomyostimulator.
AB  - Dynamic cardiomyoplasty was performed in a patient using a new cardio
      myostimulator (LD-PACE II) designed to enable a novel stimulation regimen that
      utilizes a new range of stimulation options, including cessation during sleep.
      After treatment, left ventricular ejection fraction improved in 24 months from
      15% to 25% and New York Heart Association classification improved from class IV
      to II.

PMID- 12213758
TI  - Correction of absent pulmonary valve syndrome using a pericardial valved conduit.
AB  - Absent pulmonary valve syndrome in a 4-month-old infant was successfully
      corrected using a fresh autologous pericardial trileaflet valved conduit. He
      recovered from operation with only mild pulmonary regurgitation at 4 months
      postoperatively. This technique is an effective alternative for infants with
      congenital heart disease who need tissue valved conduits. It may be more suitable
      than the aortic homograft by reason of the shortage of small homografts and its
      lower costs.

PMID- 12213757
TI  - Goldenhar's Syndrome.
AB  - A 12-year-old male was admitted with postaxial polydactyly on the right hand,
      congenital heart disease, vertebral anomaly, and facial asymmetry. Investigations
      confirmed the diagnosis of a congenital disease, Goldenhar's syndrome, with the
      rare associations of polydactyly and probable autosomal dominant inheritance.

PMID- 12213759
TI  - Acromegaly: a rare manifestation of bronchial carcinoid.
AB  - Bronchial carcinoids usually present with pulmonary symptoms. Neurohumoral
      manifestations in the form of acromegaly and Cushing's syndrome are rarely
      encountered. We report a case of bronchial carcinoid with features of acromegaly
      due to ectopic production of growth hormone-releasing hormone. Surgical resection
      of the lung lesion resulted in regression of acromegalic features, normalization
      of growth hormone secretory dynamics, and remarkable diminution of pituitary size
      seen on magnetic resonance imaging.

PMID- 12213760
TI  - Wegener's granulomatosis presenting as necrosis of the left mainstem bronchus.
AB  - A patient with pansinusitis, nasal septum necrosis, and saddle nose deformity
      showed necrosis of the left mainstem, upper, and lower bronchi, with complete
      loss of left lung perfusion and ventilation. Pneumonectomy was performed.
      Histological findings showed extensive necrotizing and granulomatous bronchial
      inflammation with vasculitis of the bronchial arteries and the pulmonary vein.
      Wegener's granulomatosis was diagnosed, despite a negative cytoplasmic pattern of
      antineutrophil cytoplasmic antibodies and the lack of renal involvement.

PMID- 12213761
TI  - Retroesophageal hematoma caused by fish bone perforation of the esophagus.
AB  - A 39-year-old man complained of acute dysphagia and dorsal pain while eating
      fish. Radiologic and endoscopic studies revealed a retroesophageal mass, which
      was later shown to be a hematoma.

PMID- 12213762
TI  - Plasmacytoma of the rib in young male.
AB  - Solitary plasmacytoma of the 11th rib with soft tissue extension was seen in a 29
      year-old male. Hematological and biochemical profiles did not reveal any systemic
      involvement. The 12-cm fusiform expansile lesion was excised and subjected to
      histopathological examination. The sections revealed sheets of plasma cells with
      focal cortical discontinuity and adjacent soft tissue invasion. This case is
      unique in view of the age of occurrence and the site of the lesion.

PMID- 12213763
TI  - Reappraisal of fascia lata grafts for reconstruction of chest wall defects.
AB  - Large chest wall defects require surgical reconstruction to ensure structural
      stability and to prevent flail chest. We used autologous fascia lata grafts to
      reconstruct skeletal chest wall defects in 8 consecutive patients. Sufficient
      chest wall stability was obtained; and no complications, such as flail chest,
      infection, or seroma, have been observed in any of the cases to date.

PMID- 12213764
TI  - Giant left ventricular aneurysm.

PMID- 12213765
TI  - Pericardiectomy for chronic constrictive pericarditis.

PMID- 12213766
TI  - Outcome of cardiac and thoracic aortic operation in patients over 80 years old.

PMID- 12213767
TI  - Patterns of positive selection in the complete NBS-LRR gene family of Arabidopsis
      thaliana.
AB  - Plant disease resistance genes have been shown to be subject to positive
      selection, particularly in the leucine rich repeat (LRR) region that may
      determine resistance specificity. We performed a genome-wide analysis of positive
      selection in members of the nucleotide binding site (NBS)-LRR gene family of
      Arabidopsis thaliana. Analyses were possible for 103 of 163 NBS-LRR nucleotide
      sequences in the genome, and the analyses uncovered substantial evidence of
      positive selection. Sites under positive selection were detected and identified
      for 10 sequence groups representing 53 NBS-LRR sequences. Functionally
      characterized Arabidopsis resistance genes were in these 10 groups, but several
      groups with extensive evidence of positive selection contained no previously
      characterized resistance genes. Amino acid residues under positive selection were
      identified, and these residues were mapped onto protein secondary structure.
      Positively selected positions were disproportionately located in the LRR domain
      (P < 0.001), particularly a nine-amino acid beta-strand submotif that is likely
      to be solvent exposed. However, a substantial proportion (30%) of positively
      selected sites were located outside LRRs, suggesting that regions other than the
      LRR may function in determining resistance specificity. Because of the unusual
      sequence variability in the LRRs of this class of proteins, secondary-structure
      analysis identifies LRRs that are not identified by similarity analyses alone.
      LRRs also contain substantial indel variation, suggesting elasticity in LRR
      length could also influence resistance specificity.

PMID- 12213768
TI  - Four-hundred million years of conserved synteny of human Xp and Xq genes on three
      Tetraodon chromosomes.
AB  - The freshwater pufferfish Tetraodon nigroviridis (TNI) has become highly
      attractive as a compact reference vertebrate genome for gene finding and
      validation. We have mapped genes, which are more or less evenly spaced on the
      human chromosomes 9 and X, on Tetraodon chromosomes using fluorescence in situ
      hybridization (FISH), to establish syntenic relationships between Tetraodon and
      other key vertebrate genomes. PufferFISH revealed that the human X is an
      orthologous mosaic of three Tetraodon chromosomes. More than 350 million years
      ago, an ancestral vertebrate autosome shared orthologous Xp and Xq genes with
      Tetraodon chromosomes 1 and 7. The shuffled order of Xp and Xq orthologs on their
      syntenic Tetraodon chromosomes can be explained by the prevalence of evolutionary
      inversions. The Tetraodon 2 orthologous genes are clustered in human Xp11 and
      represent a recent addition to the eutherian X sex chromosome. The human
      chromosome 9 and the avian Z sex chromosome show a much lower degree of synteny
      conservation in the pufferfish than the human X chromosome. We propose that a
      special selection process during vertebrate evolution has shaped a highly
      conserved array(s) of X-linked genes long before the X was used as a mammalian
      sex chromosome and many X chromosomal genes were recruited for reproduction
      and/or the development of cognitive abilities. [Sequence data reported in this
      paper have been deposited in GenBank and assigned the following accession no:
      AJ308098.]

PMID- 12213769
TI  - Comparative genomic sequence analysis of the human chromosome 21 Down syndrome
      critical region.
AB  - Comprehensive knowledge of the gene content of human chromosome 21 (HSA21) is
      essential for understanding the etiology of Down syndrome (DS). Here we report
      the largest comparison of finished mouse and human sequence to date for a 1.35-Mb
      region of mouse chromosome 16 (MMU16) that corresponds to human chromosome
      21q22.2. This includes a portion of the commonly described "DS critical region,"
      thought to contain a gene or genes whose dosage imbalance contributes to a number
      of phenotypes associated with DS. We used comparative sequence analysis to
      construct a DNA feature map of this region that includes all known genes, plus
      144 conserved sequences > or =100 bp long that show > or =80% identity between
      mouse and human but do not match known exons. Twenty of these have matches to
      expressed sequence tag and cDNA databases, indicating that they may be
      transcribed sequences from chromosome 21. Eight putative CpG islands are found at
      conserved positions. Models for two human genes, DSCR4 and DSCR8, are not
      supported by conserved sequence, and close examination indicates that low-level
      transcripts from these loci are unlikely to encode proteins. Gene prediction
      programs give different results when used to analyze the well-conserved regions
      between mouse and human sequences. Our findings have implications for evolution
      and for modeling the genetic basis of DS in mice.

PMID- 12213771
TI  - Methylation-spanning linker libraries link gene-rich regions and identify
      epigenetic boundaries in Zea mays.
AB  - Complex cereal genomes are largely composed of small gene-rich regions intermixed
      with 5 kb to 200 kb blocks of repetitive DNA. The repetitive DNA blocks are
      usually 5-methylated at 5'-CG-3' and 5'-CNG-3' cytosines in most or all adult
      tissues, while the genes are generally unmethylated at these sites. We have
      developed methylation-spanning linker library (MSLL) technology as a tool to span
      large methylated DNA blocks and thereby link unmethylated genic regions. MSLL
      clones contain insertions of large fragments that are size fractionated over gels
      after complete digestion of total genomic DNA with restriction enzymes that are
      sensitive to the 5-methylation of cytosines in 5'-CG-3' and 5'-CNG-3' sequences.
      Our data indicate that the end sequences of maize MSLL clones are greatly
      depleted in repetitive DNAs and enriched in genes relative to total genomic DNA.
      Combined with other gene-enrichment approaches, MSLL technology can efficiently
      generate fully-linked contiguous sequences in complex genomes that are resistant
      to shotgun sequencing.

PMID- 12213772
TI  - Deterministic mutation rate variation in the human genome.
AB  - Several studies of substitution rate variation have indicated that the local
      mutation rate varies over the mammalian genome. In the present study, we show
      significant variation in substitution rates within the noncoding part of the
      human genome using 4.7 Mb of human-chimpanzee pairwise comparisons. Moreover, we
      find a significant positive covariation of lineage-specific chimpanzee and human
      local substitution rates, and very similar mean substitution rates down the two
      lineages. The substitution rate variation is probably not caused by selection or
      biased gene conversion, and so we conclude that mutation rates vary
      deterministically across the noncoding nonrepetitive regions of the human genome.
      We also show that noncoding substitution rates are significantly affected by G+C
      base composition, partly because the base composition is not at equilibrium.

PMID- 12213773
TI  - Genome-wide analysis of the odorant-binding protein gene family in Drosophila
      melanogaster.
AB  - Olfaction is of considerable importance to many insects in behaviors critical for
      survival and reproduction, including location of food sources, selection of
      mates, recognition of colony con-specifics, and determination of oviposition
      sites. An ubiquitous, but poorly understood, component of the insect's olfactory
      system is a group of odorant-binding proteins (OBPs) that are present at high
      concentrations in the aqueous lymph surrounding the dendrites of olfactory
      receptor neurons. OBPs are believed to shuttle odorants from the environment to
      the underlying odorant receptors, for which they could potentially serve as
      odorant presenters. Here we show that the Drosophila genome carries 51 potential
      OBP genes, a number comparable to that of its odorant-receptor genes. We find
      that the majority (73%) of these OBP-like genes occur in clusters of as many as
      nine genes, in contrast to what has been observed for the Drosophila odorant
      receptor genes. Two of the presumptive OBP gene clusters each carries an odorant
      receptor gene. We also report an intriguing subfamily of 12 putative OBPs that
      share a unique C-terminal structure with three conserved cysteines and a
      conserved proline. Members of this subfamily have not previously been described
      for any insect. We have performed phylogenetic analyses of the OBP-related
      proteins in Drosophila as well as other insects, and we discuss the duplication
      and divergence of the genes for this large family. [The sequence data from this
      study have been submitted to FlyBase. Annotations for these sequences are
      available as supplementary material at http://www.genome.org.]

PMID- 12213770
TI  - Active Alu element "A-tails": size does matter.
AB  - Long and short interspersed elements (LINEs and SINEs) are retroelements that
      make up almost half of the human genome. L1 and Alu represent the most prolific
      human LINE and SINE families, respectively. Only a few Alu elements are able to
      retropose, and the factors determining their retroposition capacity are poorly
      understood. The data presented in this paper indicate that the length of Alu "A
      tails" is one of the principal factors in determining the retropositional
      capability of an Alu element. The A stretches of the Alu subfamilies analyzed,
      both old (Alu S and J) and young (Ya5), had a Poisson distribution of A-tail
      lengths with a mean size of 21 and 26, respectively. In contrast, the A-tails of
      very recent Alu insertions (disease causing) were all between 40 and 97 bp in
      length. The L1 elements analyzed displayed a similar tendency, in which the
      "disease"-associated elements have much longer A-tails (mean of 77) than do the
      elements even from the young Ta subfamily (mean of 41). Analysis of the draft
      sequence of the human genome showed that only about 1000 of the over one million
      Alu elements have tails of 40 or more adenosine residues in length. The presence
      of these long A stretches shows a strong bias toward the actively amplifying
      subfamilies, consistent with their playing a major role in the amplification
      process. Evaluation of the 19 Alu elements retrieved from the draft sequence of
      the human genome that are identical to the Alu Ya5a2 insert in the NF1 gene
      showed that only five have tails with 40 or more adenosine residues. Sequence
      analysis of the loci with the Alu elements containing the longest A-tails (7 of
      the 19) from the genomes of the NF1 patient and the father revealed that there
      are at least two loci with A-tails long enough to serve as source elements within
      our model. Analysis of the A-tail lengths of 12 Ya5a2 elements in diverse human
      population groups showed substantial variability in both the Alu A-tail length
      and sequence homogeneity. On the basis of these observations, a model is
      presented for the role of A-tail length in determining which Alu elements are
      active.

PMID- 12213774
TI  - Impact of the presence of paralogs on sequence divergence in a set of mouse-human
      orthologs.
AB  - Using a large set of orthologous human and mouse gene pairs, we have
      characterized genes that have been retained in duplicate in human over timescales
      comparable to the time of speciation of human and mouse. Orthologous gene pairs
      for which a paralogous gene has been present for much or all of the time since
      speciation show an increased rate of nonsynonymous substitution. We have related
      rate of divergence to functional classification using the Gene Ontology terms.
      Protein function was found, in some cases, to have a larger impact on rate of
      evolution than the presence or absence of a paralog. No evidence was found that
      genes that have been retained in duplicate are weighted toward any functional
      categories. An increase in the ratio of nonsynonymous to synonymous changes
      following duplication has previously been reported. However, because amino acid
      sequences include conservative as well as more freely evolving sites, the ratio
      of nonsynonymous to synonymous changes tends to be higher for closely related
      pairs. By measuring the divergence of orthologs only and comparing between genes
      for which a paralogous gene is either present or absent, we have compared gene
      pairs that share a common divergence time. We have also found that shorter genes
      have a higher probability of being found duplicated in the human genome, possibly
      reflecting a mutational effect.

PMID- 12213775
TI  - Splice variation in mouse full-length cDNAs identified by mapping to the mouse
      genome.
AB  - We mapped the collection of The Institute of Physical and Chemical Research
      (Japan) (RIKEN) 21,076 full-length mouse cDNA clone sequences and the mouse
      RefSeq sequences to the recently completed draft of the mouse genome. Using this
      mapping, we identified 3674 mouse genes with multiple transcripts, of which 1098
      have splice variants. All but 532 of 21,076 clones (97.5%) mapped to the genome
      assembly. Alignments of cDNA clone sequences with proteins show that much of the
      detected splice variation alters coding regions and affects the translated
      protein. We developed novel analytical techniques to classify observed splice
      variation and to assess the relation between splice variation and alternative
      transcription. This analysis indicates that an alternative choice of
      transcription start or polyadenylation signal frequently induces splice
      variation.

PMID- 12213776
TI  - Temperature-regulated transcription in the pathogenic fungus Cryptococcus
      neoformans.
AB  - The basidiomycete fungus Cryptococcus neoformans is an opportunistic pathogen of
      worldwide importance that causes meningitis, leading to death in
      immunocompromised individuals. Unlike many basidiomycete fungi, C. neoformans is
      thermotolerant, and its ability to grow at 37 degrees C is considered to be a
      virulence factor. We used serial analysis of gene expression (SAGE) to
      characterize the transcriptomes of C. neoformans strains that represent two
      varieties with different polysaccharide capsule serotypes. These include a
      serotype D strain of the C. neoformans variety neoformans and a serotype A strain
      of variety grubii. In this report, we describe the construction and
      characterization of SAGE libraries from each strain grown at 25 degrees C and 37
      degrees C. The SAGE data reveal transcriptome differences between the two
      strains, even at this early stage of analysis, and identify sets of genes with
      higher transcript levels at 25 degrees C or 37 degrees C. Notably, growth at the
      lower temperature increased transcript levels for histone genes, indicating a
      general influence of temperature on chromatin structure. At 37 degrees C, we
      noted elevated transcript levels for several genes encoding heat shock proteins
      and translation machinery. Some of these genes may play a role in temperature
      regulated phenotypes in C. neoformans, such as the adaptation of the fungus to
      growth in the host and the dimorphic transition between budding and filamentous
      growth. Overall, this work provides the most comprehensive gene expression data
      available for C. neoformans; this information will be a critical resource both
      for gene discovery and genome annotation in this pathogen.

PMID- 12213777
TI  - iFRET: an improved fluorescence system for DNA-melting analysis.
AB  - Fluorescence resonance energy transfer (FRET) is a powerful tool for detecting
      spatial relationships between macromolecules, one use of which is the tracking of
      DNA hybridization status. The process involves measuring changes in fluorescence
      as FRET donor and acceptor moieties are brought closer together or moved farther
      apart as a result of DNA hybridization/denaturation. In the present study, we
      introduce a new version of FRET, which we term induced FRET (iFRET), that is
      ideally suited for melting curve analysis. The innovation entails using a double
      strand, DNA-specific intercalating dye (e.g., SYBR Green I) as the FRET donor,
      with a conventional FRET acceptor affixed to one of the DNA molecules. The SNP
      genotyping technique dynamic allele specific hybridization (DASH) was used as a
      platform to compare iFRET to two alternative fluorescence strategies, namely, the
      use of the intercalating dye alone and the use of a standard FRET pair
      (fluorescein as donor, 6-rhodamine as acceptor). The iFRET configuration combines
      the advantages of intercalating dyes, such as high signal strengths and low cost,
      with maintaining the specificity and multiplex potential afforded by traditional
      FRET detection systems. Consequently, iFRET represents a fresh and attractive
      schema for monitoring interactions between DNA molecules.

PMID- 12213779
TI  - GAZE: a generic framework for the integration of gene-prediction data by dynamic
      programming.
AB  - We describe a method (implemented in a program, GAZE) for assembling arbitrary
      evidence for individual gene components (features) into predictions of complete
      gene structures. Our system is generic in that both the features themselves, and
      the model of gene structure against which potential assemblies are validated and
      scored, are external to the system and supplied by the user. GAZE uses a dynamic
      programming algorithm to obtain the highest scoring gene structure according to
      the model and posterior probabilities that each input feature is part of a gene.
      A novel pruning strategy ensures that the algorithm has a run-time effectively
      linear in sequence length. To demonstrate the flexibility of our system in the
      incorporation of additional evidence into the gene prediction process, we show
      how it can be used to both represent nonstandard gene structures (in the form of
      trans-spliced genes in Caenorhabditis elegans), and make use of similarity
      information (in the form of Expressed Sequence Tag alignments), while requiring
      no change to the underlying software. GAZE is available at
      http://www.sanger.ac.uk/Software/analysis/GAZE.

PMID- 12213778
TI  - Detection and visualization of compositionally similar cis-regulatory element
      clusters in orthologous and coordinately controlled genes.
AB  - Evolutionarily conserved noncoding genomic sequences represent a potentially rich
      source for the discovery of gene regulatory regions. However, detecting and
      visualizing compositionally similar cis-element clusters in the context of
      conserved sequences is challenging. We have explored potential solutions and
      developed an algorithm and visualization method that combines the results of
      conserved sequence analyses (BLASTZ) with those of transcription factor binding
      site analyses (MatInspector) (http://trafac.chmcc.org). We define hits as the
      density of co-occurring cis-element transcription factor (TF)-binding sites
      measured within a 200-bp moving average window through phylogenetically conserved
      regions. The results are depicted as a Regulogram, in which the hit count is
      plotted as a function of position within each of the two genomic regions of the
      aligned orthologs. Within a high-scoring region, the relative arrangement of
      shared cis-elements within compositionally similar TF-binding site clusters is
      depicted in a Trafacgram. On the basis of analyses of several training data sets,
      the approach also allows for the detection of similarities in composition and
      relative arrangement of cis-element clusters within nonorthologous genes,
      promoters, and enhancers that exhibit coordinate regulatory properties. Known
      functional regulatory regions of nonorthologous and less-conserved orthologous
      genes frequently showed cis-element shuffling, demonstrating that compositional
      similarity can be more sensitive than sequence similarity. These results show
      that combining sequence similarity with cis-element compositional similarity
      provides a powerful aid for the identification of potential control regions.

PMID- 12213780
TI  - Mutation detection using mass spectrometric separation of tiny oligonucleotide
      fragments.
AB  - A DNA mutation detection protocol able to identify and characterize a previously
      unknown change in a given sequence in a rapid, efficient, sensitive, and
      inexpensive manner is required to take advantage of the resources now available
      to researchers through the genome sequencing projects. We have developed a method
      based on base-specific cleavage of polymerase chain reaction (PCR) products and
      then separation of the fragments by matrix-assisted laser desorption ionization
      mass spectrometry (MALDI-MS), which can meet these criteria. Differences are seen
      as the presence, absence, or mass change of peaks corresponding to fragments
      affected by the base difference. This technique is shown through the detection of
      a polymorphism in the 3' untranslated region of IL12p40 from a double-stranded
      PCR product, and the detection of a single nucleotide polymorphism between two
      mouse strains. The sensitivity of the technique can be increased with the use of
      postsource decay, which enables differentiation of two fragments of identical
      mass but different sequence. The level of specificity and the rapid sample
      analysis time lend this technique to the mass screening of individuals for
      sequence changes and, in combination with MS sequencing methods, could be used to
      facilitate rapid resequencing of DNA.

PMID- 12213781
TI  - Conditionally amplifiable BACs: switching from single-copy to high-copy vectors
      and genomic clones.
AB  - The widely used, very-low-copy BAC (bacterial artificial chromosome) vectors are
      the mainstay of present genomic research. The principal advantage of BACs is the
      high stability of inserted clones, but an important disadvantage is the low yield
      of DNA, both for vectors alone and when carrying genomic inserts. We describe
      here a novel class of single-copy/high-copy (SC/HC) pBAC/oriV vectors that retain
      all the advantages of low-copy BAC vectors, but are endowed with a conditional
      and tightly controlled oriV/TrfA amplification system that allows: (1) a yield of
      ~100 copies of the vector per host cell when conditionally induced with L
      arabinose, and (2) analogous DNA amplification (only upon induction and with copy
      number depending on the insert size) of pBAC/oriV clones carrying >100-kb
      inserts. Amplifiable clones and libraries facilitate high-throughput DNA
      sequencing and other applications requiring HC plasmid DNA. To turn on DNA
      amplification, which is driven by the oriV origin of replication, we used copy-up
      mutations in the gene trfA whose expression was very tightly controlled by the
      araC-P(araBAD) promoter/regulator system. This system is inducible by L
      arabinose, and could be further regulated by glucose and fucose. Amplification of
      DNA upon induction with L-arabinose and its modulation by glucose are robust and
      reliable. Furthermore, we discovered that addition of 0.2% D-glucose to the
      growth medium helped toward the objective of obtaining a real SC state for all
      BAC systems, thus enhancing the stability of their maintenance, which became
      equivalent to cloning into the host chromosome

PMID- 12213782
TI  - Physical maps for genome analysis of serotype A and D strains of the fungal
      pathogen Cryptococcus neoformans.
AB  - The basidiomycete fungus Cryptococcus neoformans is an important opportunistic
      pathogen of humans that poses a significant threat to immunocompromised
      individuals. Isolates of C. neoformans are classified into serotypes (A, B, C, D,
      and AD) based on antigenic differences in the polysaccharide capsule that
      surrounds the fungal cells. Genomic and EST sequencing projects are underway for
      the serotype D strain JEC21 and the serotype A strain H99. As part of a genomics
      program for C. neoformans, we have constructed fingerprinted bacterial artificial
      chromosome (BAC) clone physical maps for strains H99 and JEC21 to support the
      genomic sequencing efforts and to provide an initial comparison of the two
      genomes. The BAC clones represented an estimated 10-fold redundant coverage of
      the genomes of each serotype and allowed the assembly of 20 contigs each for H99
      and JEC21. We found that the genomes of the two strains are sufficiently distinct
      to prevent coassembly of the two maps when combined fingerprint data are used to
      construct contigs. Hybridization experiments placed 82 markers on the JEC21 map
      and 102 markers on the H99 map, enabling contigs to be linked with specific
      chromosomes identified by electrophoretic karyotyping. These markers revealed
      both extensive similarity in gene order (conservation of synteny) between JEC21
      and H99 as well as examples of chromosomal rearrangements including inversions
      and translocations. Sequencing reads were generated from the ends of the BAC
      clones to allow correlation of genomic shotgun sequence data with physical map
      contigs. The BAC maps therefore represent a valuable resource for the generation,
      assembly, and finishing of the genomic sequence of both JEC21 and H99. The
      physical maps also serve as a link between map-based and sequence-based data,
      providing a powerful resource for continued genomic studies

PMID- 12213783
TI  - Mice deficient in small leucine-rich proteoglycans: novel in vivo models for
      osteoporosis, osteoarthritis, Ehlers-Danlos syndrome, muscular dystrophy, and
      corneal diseases.
AB  - Small leucine-rich proteoglycans (SLRPs) are extracellular molecules that bind to
      TGFbetas and collagens and other matrix molecules. In vitro, SLRPs were shown to
      regulate collagen fibrillogenesis, a process essential in development, tissue
      repair, and metastasis. To better understand their functions in vivo, mice
      deficient in one or two of the four most prominent and widely expressed SLRPs
      (biglycan, decorin, fibromodulin, and lumican) were recently generated. All four
      SLRP deficiencies result in the formation of abnormal collagen fibrils. Taken
      together, the collagen phenotypes demonstrate a cooperative, sequential, timely
      orchestrated action of the SLRPs that altogether shape the architecture and
      mechanical properties of the collagen matrix. In addition, SLRP-deficient mice
      develop a wide array of diseases (osteoporosis, osteoarthritis, muscular
      dystrophy, Ehlers-Danlos syndrome, and corneal diseases), most of them resulting
      primarily from an abnormal collagen fibrillogenesis. The development of these
      diseases by SLRP-deficient mice suggests that mutations in SLRPs may be part of
      undiagnosed predisposing genetic factors for these diseases. Although the
      distinct phenotypes developed by the different singly deficient mice point to
      distinct in vivo function for each SLRP, the analysis of the double-deficient
      mice also demonstrates the existence of rescuing/compensation mechanisms,
      indicating some functional overlap within the SLRP family.

PMID- 12213784
TI  - Dermatan sulfate: new functions from an old glycosaminoglycan.
AB  - Glycosaminoglycans constitute a considerable fraction of the glycoconjugates
      found on cellular membranes and in the extracellular matrix of virtually all
      mammalian tissues. Their ability to bind and alter protein-protein interactions
      or enzymatic activity has identified them as important determinants of cellular
      responsiveness in development, homeostasis, and disease. Although heparan sulfate
      tends to be emphasized as the most biologically active glycosaminoglycan,
      dermatan sulfate is a particularly attractive subject for further study because
      it is expressed in many mammalian tissues and it is the predominant glycan
      present in skin. Dermatan and dermatan sulfate proteoglycans have also been
      implicated in cardiovascular disease, tumorigenesis, infection, wound repair, and
      fibrosis. Growing evidence suggests that this glycosaminoglycan, like the better
      studied heparin and heparan sulfate, is an important cofactor in a variety of
      cell behaviors.

PMID- 12213785
TI  - Neisseria gonorrhoeae strain PID2 simultaneously expresses six chemically related
      lipooligosaccharide structures.
AB  - Neisseria gonorrhoeae strain PID2 was isolated from a woman suffering from pelvic
      inflammatory disease. When LOS expressed by this strain is analyzed on SDS-PAGE
      gels, at least six different lipooligosaccharide (LOS) components are visualized.
      We characterized the LOSs made by this strain by exoglycosidase digestion, sugar
      composition analysis, mass spectrometry, and analysis of the genes needed for its
      synthesis. DNA sequence analysis showed that the lgt gene cluster in this strain
      has undergone a rearrangement and that it possesses two copies of lgtA, one copy
      of lgtB and lgtC, and a hybrid gene containing sequences from lgtB and lgtE. We
      determined that the hybrid lgtB/E gene retained the lgtE gene function. DNA
      sequence analysis of the gene organization suggested that an intramolecular
      recombination between lgtA and lgtD and lgtB and lgtE had occurred via homologous
      recombination between similar sequences. Our studies demonstrated that
      fluorophore-assisted carbohydrate electrophoresis can be utilized to rapidly
      determine the composition of LOS. By combining exoglycosidase digestion, in
      combination with mass spectrometry analysis and compositional analysis, the data
      indicate that all of the LOS components produced by PID2 extend off of the alpha
      chain. The longest alpha chain oligosaccharide structure is Gal-GlcNAc-Gal-GlcNAc
      Gal-Glc-Heptose I, and the six LOS components are built up by sequentially adding
      sugars onto the first heptose. PID2 LOS is the first Neisserial LOS to be shown
      to be devoid of phosphoethanolamine modifications. Because PID2 can surface
      express its LOS, it indicates that the addition of phosphoethanolamine is not
      required for LOS surface expression.

PMID- 12213786
TI  - Contribution of the putative heparan sulfate-binding motif BBXB of RANTES to
      transendothelial migration.
AB  - The chemokines are a family of small chemoattractant proteins that have a range
      of functions, including activation and promotion of vectorial migration of
      leukocytes. Regulation on activation, normal T cell expressed and secreted
      (RANTES; CCL5), a member of the CC-chemokine subfamily, has been implicated in a
      variety of immune responses. In addition to the interaction of CC-chemokines with
      their cognate cell-surface receptors, it is known that they also bind to
      glycosaminoglycans (GAGs), including heparan sulfate. This potential for binding
      to GAG components of proteoglycans on the cell surface or within the
      extracellular matrix might allow formation of the stable chemokine concentration
      gradients necessary for leukocyte chemotaxis. In this study, we created a panel
      of mutant RANTES molecules containing neutral amino acid substitutions within
      putative, basic GAG-binding domains. Despite showing reduced binding to GAGs, it
      was found that each mutant containing a single amino acid substitution induced a
      similar leukocyte chemotactic response within a concentration gradient generated
      by free solute diffusion. However, we found that the mutant K45A had a
      significantly reduced potential to stimulate chemotaxis across a monolayer of
      microvascular endothelial cells. Significantly, this mutant bound to the CCR5
      receptor and showed a potential to mobilize Ca(2+) with an affinity similar to
      the wild-type protein. These results show that the interaction between RANTES and
      GAGs is not necessary for specific receptor engagement, signal transduction, or
      leukocyte migration. However, this interaction is required for the induction of
      efficient chemotaxis through the extracellular matrix between confluent
      endothelial cells.

PMID- 12213787
TI  - Tumor-related expression of alpha1,2fucosylated antigens on colorectal carcinoma
      cells and its suppression by cell-mediated priming using sugar acceptors for
      alpha1,2fucosyltransferase.
AB  - The accumulation of alpha1,2fucosylated antigens, such as Y
      (Fucalpha1,2Galbeta1,4 [Fucalpha1,3]GlcNAcbeta), Le(b) (Fucalpha1,2Galbeta1,3
      [Fucalpha1,4]GlcNAcbeta), and H type 2 (Fucalpha1,2 Galbeta1,4GlcNAcbeta) occurs
      specifically within human colorectal tumor tissues and can be detected by an
      antifucosylated antigen antibody, such as the YB-2 antibody. In the present
      investigation, we found that the expression of these antigens bearing an alpha1,2
      linked fucose correlated with the resistance of the tumor cells to anticancer
      treatments. Addition of an exogenous sugar acceptor for
      alpha1,2fucosyltransferase to the cell medium resulted in suppression of
      alpha1,2fucosylated antigen expression on the tumor cells and increased
      susceptibility to anticancer treatment. The increased susceptibility may be
      attributed to cancer cell-mediated priming by sugar acceptors for
      alpha1,2fucosyltransferase added to the medium.

PMID- 12213789
TI  - Constitutively unmasked CD22 on B cells of ST6Gal I knockout mice: novel
      sialoside probe for murine CD22.
AB  - The interaction of CD22 with glycoprotein ligands bearing the Siaalpha2,6Gal-R
      sequence is believed to modulate its function as a regulator of B cell signaling.
      Although a commercial sialoside-polyacrylamide (PAA) probe, NeuAc- alpha2,6Gal
      PAA, has facilitated studies on ligand binding by human CD22, murine CD22 binds
      instead with high affinity to NeuGcalpha2,6Gal-R. A multivalent probe with this
      sequence was constructed to facilitate investigations of ligand binding in CD22
      function using genetically defined murine models. The probe is based on the
      sialoside-PAA platform, which is then biotinylated for easy detection. A series
      of sialoside probes were constructed with two different length linker arms
      between the sialoside and the backbone and three different sialoside to PAA molar
      ratios. The NeuGcalpha2,6Gal-PAA probe is specific for CD22: it binds to
      sialidase-treated B cells of wild-type mice but not B cells of CD22-null mice.
      Additionally, because the probe only binds to sialidase-treated wild-type cells,
      it confirms that CD22 is constitutively "masked" on most B cells from wild-type
      mice by binding to ligands in cis. In contrast, the probe bound equally well to
      native or sialidase-treated B cells from the immunocompromised ligand-deficient
      ST6Gal I knockout mice, demonstrating that CD22 is constitutively "unmasked" in
      these cells.

PMID- 12213788
TI  - Expression and characterization of a human cDNA that complements the temperature
      sensitive defect in dolichol kinase activity in the yeast sec59-1 mutant: the
      enzymatic phosphorylation of dolichol and diacylglycerol are catalyzed by
      separate CTP-mediated kinase activities in Saccharomyces cerevisiae.
AB  - Dolichol kinase (DK) catalyzes the CTP-mediated phosphorylation of dolichol in
      eukaryotic cells, the terminal step in dolichyl monophosphate (Dol-P)
      biosynthesis de novo. In S. cerevisiae, the SEC59 gene encodes a protein
      essential for the expression of DK, an enzyme activity that is required for cell
      viability and normal rates of lipid intermediate synthesis and protein N
      glycosylation. This study identifies a cDNA clone from human brain that encodes
      the mammalian homolog of DK (hDK1p). hDK1 is capable of complementing the growth
      defect, elevating DK activity, and consequently increasing Dol-P levels in vivo
      and restoring normal N-glycosylation of carboxypeptidase Y at the restrictive
      temperature in the temperature-sensitive mutant sec59-1. The CTP-mediated
      phosphorylation of diacylglycerol (DAG) is unaffected by either the temperature
      sensitive mutation in the sec59-1 strain, overexpression of the SEC59 gene, or
      the mammalian homolog hDK1 under conditions that produced a loss or elevation in
      the level of DK activity. Additionally, overexpression of hDK1p in Sf-9 cells
      resulted in a 15-fold increase in DK activity but not DAG kinase activity in
      crude microsomal fractions. The cloned cDNA contains an open reading frame that
      would encode a protein with 538 amino acids and a molecular weight of 59,268 kDa.
      Consistent with this prediction, new polypeptides were detected with an apparent
      molecular weight of 59-60 kDa when His(6)-tagged constructs of hDK1 or the SEC59
      gene were expressed in Sf-9 cells or the temperature-sensitive sec59-1 mutant
      cells, respectively. These results identify the first cDNA clone encoding a
      protein required for the expression of DK activity, possibly the catalytic
      subunit, in a mammalian cell, and establish that the phosphorylation of dolichol
      and DAG are catalyzed by separate kinase activities in yeast.

PMID- 12213790
TI  - Heart failure: best practice and how to deliver it.

PMID- 12213791
TI  - Best practice: evidence from the clinical trials.

PMID- 12213792
TI  - Contemporary management of heart failure in clinical practice.

PMID- 12213793
TI  - Unmet need for diagnosis of heart failure: the view from primary care.

PMID- 12213795
TI  - Preventing clinical heart failure: the rationale and scientific evidence.

PMID- 12213794
TI  - Screening for left ventricular dysfunction: a step too far?

PMID- 12213796
TI  - Across the interface: the hastings heart function clinic.

PMID- 12213797
TI  - Heart failure: across the interface and beyond.

PMID- 12213798
TI  - The role of the specialist nurse.

PMID- 12213799
TI  - Living with and dying from heart failure: the role of palliative care.

PMID- 12213800
TI  - Heart failure in 10 years time: focus on pharmacological treatment.

PMID- 12213801
TI  - Glutamate racemase is an endogenous DNA gyrase inhibitor.
AB  - Almost all bacteria possess glutamate racemase to synthesize d-glutamate as an
      essential component of peptidoglycans in the cell walls. The enforced production
      of glutamate racemase, however, resulted in suppression of cell proliferation. In
      the Escherichia coli JM109/pGR3 clone, the overproducer of glutamate racemase,
      the copy number (i.e. replication efficiency) of plasmid DNA declined
      dramatically, whereas the E. coli WM335 mutant that is defective in the gene of
      glutamate racemase showed little genetic competency. The comparatively low and
      high activities for DNA supercoiling were contained in the E. coli JM109/pGR3 and
      WM335 cells, respectively. Furthermore, we found that the DNA gyrase of E. coli
      was modulated by the glutamate racemase of E. coli in the presence of UDP-N
      acetylmuramyl-l-alanine, which is a peptidoglycan precursor and functions as an
      absolute activator for the racemase. This is the first finding of the enzyme
      protein participating in both d-amino acid metabolism and DNA processing.

PMID- 12213802
TI  - Ceramide and reactive oxygen species generated by H2O2 induce caspase-3
      independent degradation of Akt/protein kinase B.
AB  - This study was designed to elucidate the mechanisms leading to down-regulation of
      the Akt/protein kinase B (PKB) survival pathway during H2O2-induced cell death.
      H2O2 produced early activation of Akt/PKB and also DNA damage that was followed
      by stabilization of p53 levels, formation of reactive oxygen species (ROS), and
      generation of ceramide through activation of a glutathione-sensitive neutral
      sphingomyelinase. These events correlated with long term dephosphorylation and
      subsequent degradation of Akt. A membrane-targeted active Akt version attenuated
      apoptosis but not necrosis induced by H2O2 and was more resistant to
      dephosphorylation and proteolysis induced by apoptotic concentrations of H2O2.
      Proteolysis of Akt was prevented by exogenous addition of glutathione, indicating
      a role of ROS and ceramide in Akt degradation. However, Akt was degraded
      similarly in cells transfected with wild type and dominant negative p53 mutant,
      indicating that degradation of Akt under oxidative injury may be p53-independent.
      Specific inhibitors of caspase groups I and III prevented proteolysis of Akt/PKB
      and poly(ADP-ribose) polymerase in cells submitted to apoptotic but not necrotic
      H2O2 concentrations. Surprisingly, in caspase-3-deficient MCF-7 cells Akt was
      more sensitive to H2O2-induced degradation than the caspase-3 substrate poly(ADP
      ribose) polymerase. Moreover, the Akt/PKB double mutant Akt(D108A,D119A), which
      is not cleaved by caspase-3, and a triple mutant (D453A,D455A,D456A), which lacks
      the consensus sequence for caspase-3 cleavage, were also degraded in H2O2-treated
      cells. Our results suggest that strong oxidants generate intracellular ROS and
      ceramide which in term lead to down-regulation of Akt by dephosphorylation and
      caspase-3-independent proteolysis.

PMID- 12213803
TI  - Deciphering vascular endothelial cell growth factor/vascular permeability factor
      signaling to vascular permeability. Inhibition by atrial natriuretic peptide.
AB  - Vascular endothelial cell growth factor (VEGF) was originally described as a
      potent vascular permeability factor (VPF) that importantly contributes to
      vascular pathobiology. The signaling pathways that underlie VEGF/VPF-induced
      permeability are not well defined. Furthermore, endogenous vascular peptides that
      regulate this important VPF function are currently unknown. We report here that
      VPF significantly enhances permeability in aortic endothelial cells via a linked
      signaling pathway, sequentially involving Src, ERK, JNK, and phosphatidylinositol
      3-kinase/AKT. This leads to the serine/threonine phosphorylation and
      redistribution of actin and the tight junction (TJ) proteins, zona occludens-1
      and occludin, and the loss of the endothelial cell barrier architecture. Atrial
      natriuretic peptide (ANP) inhibited VPF signaling, TJ protein phosphorylation and
      localization, and VPF-induced permeability. This involved both guanylate cyclase
      and natriuretic peptide clearance receptors. In vivo, transgenic mice that
      overexpress ANP showed significantly less VPF-induced kinase activation and
      vascular permeability compared with non-transgenic littermates. Thus, ANP acts as
      an anti-permeability factor by inhibiting the signaling functions of VPF that we
      define here and by preserving the endothelial cell TJ functional morphology.

PMID- 12213804
TI  - Regulation of insulin receptor function by a small molecule insulin receptor
      activator.
AB  - In type 2 diabetes mellitus, impaired insulin signaling leads to hyperglycemia
      and other metabolic abnormalities. TLK19780, a non-peptide small molecule, is a
      new member of a novel class of anti-diabetic agents that function as activators
      of the insulin receptor (IR) beta-subunit tyrosine kinase. In HTC-IR cells, 20
      microm TLK19780 enhanced maximal insulin-stimulated IR autophosphorylation 2-fold
      and increased insulin sensitivity 2-3-fold. In contrast, TLK19780 did not
      potentiate the action of insulin-like growth factor-1, indicating the selectivity
      of TLK19780 toward the IR. The predominant effect of TLK19780 was to increase the
      number of IR that underwent autophosphorylation. Kinetic studies indicated that
      TLK19780 acted very rapidly, with a maximal effect observed 2 min after addition
      to insulin-stimulated cells. In 3T3-L1 adipocytes, 5 microm TLK19780 enhanced
      insulin-stimulated glucose transport, increasing both the sensitivity and maximal
      responsiveness to insulin. These studies indicate that at low micromolar levels
      small IR activator molecules can enhance insulin action in various cultured cells
      and suggest that this effect is mediated by increasing the number of IR that are
      tyrosine-phosphorylated in response to insulin. These studies suggest that these
      types of molecules could be developed to treat type 2 diabetes and other clinical
      conditions associated with insulin resistance.

PMID- 12213805
TI  - Identification of Nd1, a novel murine kelch family protein, involved in
      stabilization of actin filaments.
AB  - We isolated Nd1, a novel kelch family gene that encodes two forms of proteins,
      Nd1-L and Nd1-S. Nd1-L contains a BTB/POZ domain in its N terminus and six kelch
      repeats in the C terminus. Nd1-S has the BTB/POZ domain but lacks the six kelch
      repeats. Nd1-L but not Nd1-S mRNA is detected ubiquitously in normal mouse
      tissues. Nd1-L and Nd1-S proteins can form a dimer through the BTB/POZ domain.
      Nd1-L colocalizes with actin filaments detected using a confocal microscope, and
      its kelch repeats bind to them in vitro. Overexpression of Nd1-L in NIH3T3 cells
      delayed cell growth by affecting the transition of cytokinesis. Furthermore, the
      overexpression prevented NIH3T3 cells from cell death induced by actin
      destabilization but not by microtubule dysfunction. These data suggest that Nd1-L
      functions as a stabilizer of actin filaments as an actin-binding protein and may
      play a role in the dynamic organization of the actin cytoskeleton.

PMID- 12213806
TI  - p38 Signaling-mediated hypoxia-inducible factor 1alpha and vascular endothelial
      growth factor induction by Cr(VI) in DU145 human prostate carcinoma cells.
AB  - Chromium(VI) (Cr(VI)) is widely used in industry and is a potent inducer of
      tumors in animals. The present study demonstrates that Cr(VI) induces hypoxia
      inducible factor 1 (HIF-1) activity through the specific expression of HIF-1alpha
      but not HIF-1beta subunit and increases the level of vascular endothelial growth
      factor (VEGF) expression in DU145 human prostate carcinoma cells. To dissect the
      signaling pathways involved in Cr(VI)-induced HIF-1 expression, we found that p38
      mitogen-activated protein kinase signaling was required for HIF-1alpha expression
      induced by Cr(VI). Neither phosphatidylinositol 3-kinase nor extracellular signal
      regulated kinase activity was required for Cr(VI)-induced HIF-1 expression.
      Cr(VI) induced expression of HIF-1 and VEGF through the production of reactive
      oxygen species in DU145 cells. The major species of reactive oxygen species
      responsible for the induction of HIF-1 and VEGF expression is H(2)O(2). These
      results suggest that the expression of HIF-1 and VEGF induced by Cr(VI) may be an
      important signaling pathway in the Cr(VI)-induced carcinogenesis.

PMID- 12213807
TI  - Spatial redox regulation of a critical cysteine residue of NF-kappa B in vivo.
AB  - Reduction-oxidation (redox) regulation has been implicated in the activation of
      the transcription factor NF-kappaB. However, the significance and mechanism of
      the redox regulation remain elusive, mainly due to the technical limitations
      caused by rapid proton transfer in redox reactions and by the presence of many
      redox molecules within cells. Here we establish versatile methods for measuring
      redox states of proteins and their individual cysteine residues in vitro and in
      vivo, involving thiol-modifying reagents and LC-MS analysis. Using these methods,
      we demonstrate that the redox state of NF-kappaB is spatially regulated by its
      subcellular localization. While the p65 subunit and most cysteine residues of the
      p50 subunit are reduced similarly in the cytoplasm and in the nucleus, Cys-62 of
      p50 is highly oxidized in the cytoplasm and strongly reduced in the nucleus. The
      reduced form of Cys-62 is essential for the DNA binding activity of NF-kappaB.
      Several lines of evidence suggest that the redox factor Ref-1 is involved in Cys
      62 reduction in the nucleus. We propose that the Ref-1-dependent reduction of p50
      in the nucleus is a necessary step for NF-kappaB activation. This study also
      provides the first example of a drug that inhibits the redox reaction between two
      specific proteins.

PMID- 12213808
TI  - N-terminal sequence and distal histidine residues are responsible for pH
      regulated cytoplasmic membrane binding of human AMP deaminase isoform E.
AB  - Mammalian AMP deaminase 3 (AMPD3) enzymes reportedly bind to intracellular
      membranes, plasma lipid vesicles, and artificial lipid bilayers with associated
      alterations in enzyme conformation and function. However, proteolytic sensitivity
      of AMPD polypeptides makes it likely that prior studies were performed with N
      truncated enzymes. This study uses erythrocyte ghosts to characterize the
      reversible cytoplasmic membrane association of human full-sized recombinant
      isoform E (AMPD3). Membrane-bound isoform E exhibits diminished catalytic
      activity whereas low micromolar concentrations of the cationic antibiotic,
      neomycin, disrupt this protein-lipid interaction and relieve catalytic
      inhibition. The cytoplasmic membrane association of isoform E also displays an
      inverse correlation with pH in the physiological range. Diethyl pyrocarbonate
      (DEPC) modification of isoform E nearly abolishes its cytoplasmic membrane
      binding capacity, and this effect can be reversed by hydroxylamine. Difference
      spectra reveal that 18 of 29 histidine residues in each isoform E subunit are N
      carbethoxylated by DEPC. These combined data demonstrate that protonated
      imidazole rings of histidine residues mediate a pH-responsive association of
      isoform E with anionic charges on the surface of the cytoplasmic membrane,
      possibly phosphatidylinositol 4,5-bisphosphate, a pure noncompetitive inhibitor
      of the enzyme. Finally, AMPD1 and a series of N-truncated AMPD3 enzymes are used
      to show that these behaviors are specific to isoform E and require up to 48 N
      terminal amino acids, even though this stretch of sequence contains no histidine
      residues. The pH-responsive cytosol-membrane partitioning of isoform E may be an
      important mechanism for branch point regulation of adenylate catabolism.

PMID- 12213809
TI  - Ethanol induction of class I alcohol dehydrogenase expression in the rat occurs
      through alterations in CCAAT/enhancer binding proteins beta and gamma.
AB  - Alcohol dehydrogenase (ADH) is the principal ethanol-metabolizing enzyme. Ethanol
      induces rat Class I ADH mRNA and activity by an as yet unknown mechanism. In the
      current study, adult male rats were fed an ethanol-containing diet by continuous
      intragastric infusion for 42 days. Hepatic Class I ADH mRNA, protein, and
      activity levels in the ethanol-infused rats increased 3.9-, 3.3-, and 1.7-fold,
      respectively (p <0.05). Cis-acting elements within the proximal promoter region
      of the ADH gene were studied by electrophoretic mobility shift assay (EMSA).
      Hepatic nuclear extract (HNE) binding to either the consensus or ADH-specific
      CCAAT/enhancer binding protein (C/EBP) sites was >2.4-fold greater in ethanol-fed
      rats (p <0.05) than controls. Antibody-specific EMSA assays demonstrated binding
      of the transcription factor C/EBPbeta to the C/EBP site. Western blot immunoblot
      analysis of HNEs demonstrated 3.5- and 2.3-fold increases in C/EBPbeta (LAP) and
      C/EBPdelta (p <0.05), respectively, in ethanol-fed rats compared with controls,
      whereas levels of the truncated C/EBPbeta (LIP) and C/EBPgamma were lower in
      ethanol-fed rats (p <0.05). HNE from ethanol-fed rats increased (3-fold) the in
      vitro transcription of rat Class I ADH (p <0.05), and mutation of the C/EBP
      element in the proximal promoter region blocked this effect. Antisera against LIP
      or C/EBPgamma enhanced transcription efficiency (p <0.05). These data provide the
      first evidence for the mechanism by which ethanol regulates rat hepatic Class I
      ADH gene expression in vivo. This mechanism involves the C/EBP site and the
      enhancer binding proteins beta and gamma.

PMID- 12213810
TI  - Environmental stress causes oxidative damage to plant mitochondria leading to
      inhibition of glycine decarboxylase.
AB  - A cytotoxic product of lipid peroxidation, 4-hydroxy-2-nonenal (HNE), rapidly
      inhibited glycine, malate/pyruvate, and 2-oxoglutarate-dependent O2 consumption
      by pea leaf mitochondria. Dose- and time-dependence of inhibition showed that
      glycine oxidation was the most severely affected with a K(0.5) of 30 microm.
      Several mitochondrial proteins containing lipoic acid moieties differentially
      lost their reactivity to a lipoic acid antibody following HNE treatment. The most
      dramatic loss of antigenicity was seen with the 17-kDa glycine decarboxylase
      complex (GDC) H-protein, which was correlated with the loss of glycine-dependent
      O2 consumption. Paraquat treatment of pea seedlings induced lipid peroxidation,
      which resulted in the rapid loss of glycine-dependent respiration and loss of H
      protein reactivity with lipoic acid antibodies. Pea plants exposed to chilling
      and water deficit responded similarly. In contrast, the damage to other lipoic
      acid-containing mitochondrial enzymes was minor under these conditions. The
      implication of the acute sensitivity of glycine decarboxylase complex H-protein
      to lipid peroxidation products is discussed in the context of photorespiration
      and potential repair mechanisms in plant mitochondria.

PMID- 12213811
TI  - Molecular basis for the local conformational rearrangement of human phosphoserine
      phosphatase.
AB  - Human phosphoserine phosphatase (HPSP) regulates the levels of glycine and d
      serine, the putative co-agonists for the glycine site of the NMDA receptor in the
      brain. Here, we describe the first crystal structures of the HPSP in complexes
      with the competitive inhibitor 2-amino-3-phosphonopropionic acid (AP3) at 2.5 A,
      and the phosphate ion (Pi) and the product uncompetitive inhibitor l-serine
      (HPSP.l-Ser.Pi) at 2.8 A. The complex structures reveal that the open-closed
      environmental change of the active site, generated by local rearrangement of the
      alpha-helical bundle domain, is important to substrate recognition and
      hydrolysis. The maximal extent of this structural rearrangement is shown to be
      about 13 A at the L4 loop and about 25 degrees at the helix alpha3. Both the
      structural change and mutagenesis data suggest that Arg-65 and Glu-29 play an
      important role in the binding of the substrate. Interestingly, the AP3 binding
      mode turns out to be significantly different from that of the natural substrate,
      phospho-l-serine, and the HPSP.l-Ser.Pi structure provides a structural basis for
      the feedback control mechanism of serine. These analyses allow us to provide a
      clear model for the mechanism of HPSP and a framework for structure-based drug
      development.

PMID- 12213812
TI  - Serotonin-induced MMP-13 production is mediated via phospholipase C, protein
      kinase C, and ERK1/2 in rat uterine smooth muscle cells.
AB  - Serotonin (5-hydroxytryptamine; 5-HT), acting via the 5-HT(2A) receptor, up
      regulates the transcription and production of interstitial collagenase (matrix
      metalloproteinase-13; MMP-13), a critical enzyme responsible for maintaining the
      integrity of the uterus, after parturition. Serotonin treatment of rat uterine
      myometrial smooth muscle cells induced inositol phosphate (IP) turnover, which
      was abolished by the 5-HT(2A) receptor-specific antagonists ketanserin and
      spiperone. The phospholipase C (PLC) inhibitors and D609 attenuated serotonin
      mediated-IP turnover with a corresponding inhibition of MMP-13 protein
      production. Subsequent recovery of both MMP-13 protein expression and IP
      generation was seen following the removal of D609. Protein kinase C (PKC)
      activators, the diacylglycerol analogue 1,2-dioctanoyl-sn-glycerol and phorbol
      myristate acetate (PMA), mimicked the effect of serotonin on MMP-13 protein
      expression; prolonged PMA treatment (which down-regulates PKC) lowered MMP-13
      protein levels. The PKC-specific inhibitors bisindolylmaleimide I, calphostin C,
      CGP 41251, and the PKCdelta-selective inhibitor rottlerin were able to suppress
      serotonin up-regulation of MMP-13. Furthermore, the mitogen-activated protein
      kinase kinase (MEK) inhibitor PD98059 blocked serotonin-dependent activation of
      p44/42 MAPK (pERK1/2), a downstream effector of PKC and also down-regulated MMP
      13 protein expression. Similarly, calphostin C and rottlerin depressed activation
      of p44/42 MAPK. From these studies, serotonin, binding through the 5-HT(2A)
      receptor, initiates a signaling cascade whereby stimulation of PLC leads to the
      activation of PKC and subsequently the ERK1/2 pathway, which ultimately results
      in MMP-13 production.

PMID- 12213813
TI  - Regulation of the ETS transcription factor ER81 by the 90-kDa ribosomal S6 kinase
      1 and protein kinase A.
AB  - The ETS transcription factor ER81 is activated in response to many signals via
      mitogen-activated protein kinases (MAPKs). However, ER81 is not only
      phosphorylated on MAPK sites but also at other sites that impact on its
      transactivation potential. Here we describe that the 90-kDa ribosomal S6 kinase 1
      (RSK1), a protein kinase downstream of the extracellular signal-regulated kinase
      (ERK) subclass of MAPKs, binds to ER81, phosphorylates it, and enhances ER81
      dependent transcription. Two in vivo RSK1 phosphorylation sites within ER81,
      Ser(191) and Ser(216), were identified, whose mutation to alanine reduces ER81
      activity upon ERK-MAPK stimulation. Furthermore, RSK1 activates the ER81 cofactor
      CREB-binding protein and may thereby augment ER81-dependent transcription.
      Similar to RSK1, the cAMP-dependent protein kinase A (PKA) phosphorylates ER81 on
      Ser(191)/Ser(216). Additionally, PKA targets ER81 on Ser(334) in vivo.
      Surprisingly, phosphorylation of Ser(334) severely reduces the DNA-binding
      ability of ER81 but also enhances the transactivation potential of ER81. These
      counteractive effects of PKA phosphorylation on ER81-dependent transcription may
      cause the selective up-regulation of promoters with high but not low affinity for
      ER81. Collectively, we have identified mechanisms for how two distinct signaling
      pathways with different effector protein kinases, RSK1 and PKA, converge on ER81,
      which may regulate ER81 function during development and tumorigenesis.

PMID- 12213814
TI  - The carboxyl-terminal domains of IgA and IgM direct isotype-specific
      polymerization and interaction with the polymeric immunoglobulin receptor.
AB  - Mucosal surfaces are protected by polymeric immunoglobulins that are transported
      across the epithelium by the polymeric immunoglobulin receptor (pIgR). Only
      polymeric IgA and IgM containing a small polypeptide called the "joining" (J)
      chain can bind to the pIgR. J chain-positive IgA consists of dimers, and some
      larger polymers, whereas only IgM pentamers incorporate the J chain. We made
      domain swap chimeras between human IgA1 and IgM and found that the COOH-terminal
      domains of the heavy chains (Calpha3 and Cmu4, respectively) dictated the size of
      the polymers formed and also which polymers incorporated the J chain. We also
      showed that chimeric IgM molecules engineered to contain Calpha3 were able to
      bind the rabbit pIgR. Since the rabbit pIgR normally does not bind IgM, these
      results suggest that the COOH-terminal domain of the polymeric immunoglobulins is
      primarily responsible for interaction with the pIgR. Finally, we made a novel
      chimeric IgA immunoglobulin, containing the terminal domain from IgM. This
      recombinant molecule formed J chain-containing pentamers that could, like IgA,
      efficiently form covalent complexes with the human pIgR ectodomain, known as
      secretory component.

PMID- 12213815
TI  - Identification of direct p73 target genes combining DNA microarray and chromatin
      immunoprecipitation analyses.
AB  - The newly discovered p53 family member, p73, has a striking homology to p53 in
      both sequence and modular structure. Ectopic expression of p73 promotes
      transcription of p53 target genes and recapitulates the most characterized p53
      biological effects such as growth arrest, apoptosis, and differentiation. Unlike
      p53-deficient mice that develop normally but are subject to spontaneous tumor
      formation, p73-deficient mice exhibit severe defects in the development of
      central nervous system and suffer from inflammation but are not prone to tumor
      development. These phenotypes suggest different biological activities mediated by
      p53 and p73 that might reflect activation of specific sets of target genes. Here,
      we have analyzed the gene expression profile of H1299 cells after p73alpha or p53
      activation using oligonucleotide microarrays capable of detecting approximately
      11,000 mRNA species. Our results indicate that p73alpha and p53 activate both
      common and distinct groups of genes. We found 141 and 320 genes whose expression
      is modulated by p73alpha and p53, respectively. p73alpha up-regulates 85 genes,
      whereas p53 induces 153 genes, of which 27 are in common with p73alpha.
      Functional classification of these genes reveals that they are involved in many
      aspects of cell function ranging from cell cycle and apoptosis to DNA repair.
      Furthermore, we report that some of the up-regulated genes are directly activated
      by p73alpha or p53.

PMID- 12213816
TI  - Zinc release from protein kinase C as the common event during activation by lipid
      second messenger or reactive oxygen.
AB  - Zinc is a structural component of many regulatory molecules including
      transcription factors and signaling molecules. We report that two alternate
      signaling pathways of protein kinase C (PKC) activation involving either the
      lipid second messengers (diacylglycerol and its mimetics, the phorbol esters) or
      reactive oxygen converge at the zinc finger of the regulatory domain. They all
      trigger the release of zinc ions. An increase in intracellular free Zn(2+) was
      observed by confocal microscopy in intact cells treated with phorbol ester or by
      mild oxidation. The source of liberated Zn(2+) was traced to PKC and particularly
      the zinc finger domains. The activated form of native PKCalpha contained
      significantly less Zn(2+) than the resting form. Furthermore, purified
      recombinant PKC protein fragments shed stoichiometric amounts of Zn(2+) upon
      reaction with diacylglycerol, phorbol ester, or reactive oxygen in vitro. Our
      results offer new insight into the regulation of PKC. Far from cementing rigid
      structures, zinc actually is the linchpin that orchestrates dynamic changes in
      response to specific signals, allowing kinase activity to be turned on or off.

PMID- 12213817
TI  - A novel enhancing mechanism for hydrogen sulfide-producing activity of
      cystathionine beta-synthase.
AB  - H2S is produced from cysteine by cystathionine beta-synthase (CBS) in the brain
      and functions as a neuromodulator. Although the production of H2S is regulated by
      Ca2+ and calmodulin in response to neuronal excitation, little is known about the
      molecular mechanism for the regulation in CBS activity. Here we show that four
      cysteine residues of CBS are involved in the regulation of its activity in the
      presence of Ca2+ and calmodulin. Sodium nitroprusside (SNP), a modifying agent
      for cysteine residues, enhances CBS activity, whereas N-ethylmaleimide, an
      alkylating agent for cysteine residues, completely abolished the effect of SNP.
      Site-directed mutagenesis of the 13 cysteine residues of CBS identified four
      cysteine residues that are involved in the regulation of CBS activity by SNP, and
      two of the four residues are involved in the regulation of the basal CBS
      activity. The enhancement of CBS activity by SNP is independent of nitric oxide
      production. In the presence of Staphylococcus aureus alpha-hemolysin, which
      permeabilizes the cell membrane, exogenously applied SNP enhances the activity of
      CBS in intact cells. The present study demonstrates a novel mechanism for the
      regulation of CBS activity and provides a possible therapeutic application of SNP
      for the diseases in which CBS activity is deficient.

PMID- 12213818
TI  - Human testis/sperm-specific histone H2B (hTSH2B). Molecular cloning and
      characterization.
AB  - Human sperm, unlike the sperm of other mammals, contain replacement histones with
      unknown biological functions. Here, we report the identification of the novel
      human gene coding for a testis/sperm-specific histone H2B (hTSH2B). This variant
      histone is 85% homologous to somatic H2B and has over 93% homology with the
      testis H2B of rodents. Using genomic PCR, two genetic alleles of hTSH2B were
      found in the human population. The hTSH2B gene is transcribed exclusively in
      testis, and the corresponding protein is also present in mature sperm. We
      expressed recombinant hTSH2B and identified this protein with a particular H2B
      subtype expressed in vivo. The subnuclear distribution of H2B variants in sperm
      was determined using biochemical fractionation and immunoblotting. The H2B
      variant associated with telomere-binding activity () was solubilized by Triton X
      100 or micrococcal nuclease extraction, whereas hTSH2B was relatively tightly
      bound in nuclei. Immunofluorescence showed that hTSH2B was concentrated in spots
      located at the basal nuclear area of a subpopulation (20% of cells) of mature
      sperm. This fact may be of particular importance, because the hTSH2B "positive"
      and "negative" sperm cells may undergo significantly different decondensation
      processes following fertilization.

PMID- 12213819
TI  - Microarray analysis of insulin and insulin-like growth factor-1 (IGF-1) receptor
      signaling reveals the selective up-regulation of the mitogen heparin-binding EGF
      like growth factor by IGF-1.
AB  - Insulin and insulin-like growth factor-1 (IGF-1) act through highly homologous
      receptors that engage similar intracellular signaling pathways, yet these
      hormones serve largely distinct physiological roles in the control of metabolism
      and growth, respectively. In an attempt to uncover the molecular mechanisms
      underlying their divergent functions, we compared insulin receptor (IR) and IGF-1
      receptor (IGF-1R) regulation of gene expression by microarray analysis, using 3T3
      L1 cells expressing either TrkC/IR or TrkC/IGF-1R chimeric receptors to ensure
      the highly selective activation of each receptor tyrosine kinase. Following
      stimulation of the chimeric receptors for 4 h, we detected 11 genes to be
      differentially regulated, of which 10 were up-regulated to a greater extent by
      the IGF-1R. These included genes involved in adhesion, transcription, transport,
      and proliferation. The expression of mRNA encoding heparin-binding epidermal
      growth factor-like growth factor (HB-EGF), a potent mitogen, was markedly
      increased by IGF-1R but not IR activation. This effect was dependent on MAPK, but
      not phosphatidylinositol 3-kinase, and did not require an autocrine loop through
      the epidermal growth factor receptor. HB-EGF mitogenic activity was detectable in
      the medium of 3T3-L1 preadipocytes expressing activated IGF-1R but not IR,
      indicating that the transcriptional response is accompanied by a parallel
      increase in mature HB-EGF protein. The differential abilities of the IR and IGF
      1R tyrosine kinases to stimulate the synthesis and release of a growth factor may
      provide, at least in part, an explanation for the greater role of the IGF-1R in
      the control of cellular proliferation.

PMID- 12213820
TI  - Glucose down-regulates Per1 and Per2 mRNA levels and induces circadian gene
      expression in cultured Rat-1 fibroblasts.
AB  - In mammals, peripheral circadian clocks are present in most tissues, but little
      is known about how these clocks are synchronized with the ambient 24-h cycles. By
      using rat-1 fibroblasts, a model cell system of the peripheral clock, we found
      that an exchange of the culture medium triggered circadian gene expression that
      was preceded by slow down-regulation of Per1 and Per2 mRNA levels. This profile
      contrasts to the immediate up-regulation of these genes often observed for clock
      resetting. The screening of factor(s) responsible for the down-regulation
      revealed glucose as a key component triggering the circadian rhythm. The
      requirement of both glucose metabolism and RNA/protein synthesis for the down
      regulation suggests the involvement of gene(s) immediately up-regulated by
      glucose metabolism. An analysis with high density oligonucleotide microarrays
      identified >100 glucose-regulated genes. We found among others immediately up
      regulated genes encoding transcriptional regulators TIEG1, VDUP1, and HES1, in
      addition to cooperatively regulated genes that are associated with cholesterol
      biosynthesis and cell cycle. The immediate up-regulation of Tieg1 and Vdup1
      expression was dependent on glucose metabolism but not on protein synthesis,
      suggesting that the transcriptional regulators mediate the glucose-induced down
      regulation of Per1 and Per2 expression. These results illustrate a novel mode of
      peripheral clock resetting by external glucose, a major food metabolite.

PMID- 12213821
TI  - In vivo regulation of phosphoinositide 3-kinase in retina through light-induced
      tyrosine phosphorylation of the insulin receptor beta-subunit.
AB  - Recently, we have shown that phosphoinositide 3-kinase (PI3K) in bovine rod outer
      segment (ROS) is activated in vitro by tyrosine phosphorylation of the C-terminal
      tail of the insulin receptor (Rajala, R. V. S., and Anderson, R. E. (2001)
      Invest. Ophthal. Vis. Sci. 42, 3110-3117). In this study, we have investigated
      the in vivo mechanism of PI3K activation in the rodent retina and report the
      novel finding that light stimulates tyrosine phosphorylation of the beta-subunit
      of the insulin receptor (IRbeta) in ROS membranes, which leads to the association
      of PI3K enzyme activity with IRbeta. Retinas from light- or dark-adapted mice and
      rats were homogenized and immunoprecipitated with antibodies against
      phosphotyrosine, IRbeta, or the p85 regulatory subunit of PI3K, and PI3K activity
      was measured using PI-4,5-P(2) as substrate. We observed a light-dependent
      increase in tyrosine phosphorylation of IRbeta and an increase in PI3K enzyme
      activity in isolated ROS and in anti-phosphotyrosine and anti-IRbeta
      immunoprecipitates of retinal homogenates. The light effect was localized to
      photoreceptor neurons and is independent of insulin secretion. Our results
      suggest that light induces tyrosine phosphorylation of IRbeta in outer segment
      membranes, which leads to the binding of p85 through its N-terminal Src homology
      2 domain and the generation of PI-3,4,5-P(3). We suggest that the physiological
      role of this process may be to provide neuroprotection of the retina against
      light damage by activating proteins that protect against stress-induced
      apoptosis.

PMID- 12213822
TI  - Structural recognition by recombinant human heparanase that plays critical roles
      in tumor metastasis. Hierarchical sulfate groups with different effects and the
      essential target disulfated trisaccharide sequence.
AB  - Human heparanase is an endo-beta-d-glucuronidase that degrades heparan
      sulfate/heparin and has been implicated in a variety of biological processes,
      such as inflammation, tumor angiogenesis, and metastasis. Although the cloned
      enzyme has been demonstrated to have a critical role in tumor metastasis, the
      substrate specificity has been poorly understood. In the present study, the
      specificity of the purified recombinant human heparanase was investigated for the
      first time using a series of structurally defined oligosaccharides isolated from
      heparin/heparan sulfate. The best substrates were deltaHexUA(+/-2S)-GlcN(NS,6S)
      GlcUA-GlcN(NS,6S)-GlcUA-GlcN(NS,6S) and deltaHexUA(2S)-GlcN(NS,6S)-GlcUA
      GlcN(NS,6S) (where deltaHexUA, GlcN, GlcUA, NS, 2S, and 6S represent unsaturated
      hexuronic acid, d-glucosamine, d-glucuronic acid, 2-N-sulfate, 2-O-sulfate, and 6
      O-disulfate, respectively). Based on the percentage conversion of the substrates
      to products under identical assay conditions, several aspects of the recognition
      structures were revealed. 1) The minimum recognition backbone is the
      trisaccharide GlcN-GlcUA-GlcN. 2) The target GlcUA residues are in the sulfated
      region. 3) The -GlcN(6S)-GlcUA-GlcN(NS)- sequence is essential but not sufficient
      as the cleavage site. 4) The IdoUA(2S) residue, located two saccharides away from
      the target GlcUA residue, claimed previously to be essential, is not
      indispensable. 5) The 3-O-sulfate group on the GlcN is dispensable and even has
      an inhibitory effect when located in a highly sulfated region. 6) Based on these
      and previous results, HexUA(2S)-GlcN(NS,6S)-IdoUA-GlcNAc(6S)-GlcUA-GlcN(NS,+/-6S)
      IdoUA(2S)-GlcN(NS,6S) (where HexUA represents hexuronic acid) has been proposed
      as a probable physiological target octasaccharide sequence. These findings will
      aid establishing a quantitative assay method using the above tetrasaccharide and
      designing heparan sulfate-based specific inhibitors of the heparanase for new
      therapeutic strategies.

PMID- 12213823
TI  - SDS-resistant active and thermostable dimers are obtained from the dissociation
      of homotetrameric beta-glycosidase from hyperthermophilic Sulfolobus solfataricus
      in SDS. Stabilizing role of the A-C intermonomeric interface.
AB  - beta-Glycosidases are fundamental, widely conserved enzymes. Those from
      hyperthermophiles exhibit unusual stabilities toward various perturbants.
      Previous work with homotetrameric beta-glycosidase from hyperthermophilic
      Sulfolobus solfataricus (M(r) 226,760) has shown that addition of 0.05-0.1% SDS
      was associated with minimal secondary structure perturbations and increased
      activity. This work addresses the effects of SDS on beta-glycosidase quaternary
      structure. In 0.1-1% SDS, the enzyme was dimeric, as determined by Ferguson
      analysis of transverse-gradient polyacrylamide gels. The catalytic activity of
      the beta-glycosidase dimer in SDS was determined by in-gel assay. A minor
      decrease of thermal stability in SDS was observed after exposure to temperatures
      up to 80 degrees C for 1 h. An analysis of beta-glycosidase crystal structure
      showed different changes in solvent-accessible surface area on going from the
      tetramer to the two possible dimers (A-C and A-D). Energy minimization and
      molecular dynamics calculations showed that the A-C dimer, exhibiting the lowest
      exposed surface area, was more stabilized by a network of polar interactions. The
      charge distribution around the A-C interface was characterized by a local short
      range anisotropy, resulting in an unfavorable interaction with SDS. This paper
      provides a detailed description of an SDS-resistant inter-monomeric interface,
      which may help understand similar interfaces involved in important biological
      processes.

PMID- 12213824
TI  - Retinoid-induced G1 arrest and differentiation activation are associated with a
      switch to cyclin-dependent kinase-activating kinase hypophosphorylation of
      retinoic acid receptor alpha.
AB  - Cell cycle G(1) exit is a critical stage where cells commonly commit to
      proliferate or to differentiate, but the biochemical events that regulate the
      proliferation/differentiation (P/D) transition at G(1) exit are presently
      unclear. We previously showed that MAT1 (menage a trois 1), an assembly factor
      and targeting subunit of the cyclin-dependent kinase (CDK)-activating kinase
      (CAK), modulates CAK activities to regulate G(1) exit. Here we find that the
      retinoid-induced G(1) arrest and differentiation activation of cultured human
      leukemic cells are associated with a switch to CAK hypophosphorylation of
      retinoic acid receptor alpha (RARalpha) from CAK hyperphosphorylation of
      RARalpha. The switch to CAK hypophosphorylation of RARalpha is accompanied by
      decreased MAT1 expression and MAT1 fragmentation that occurs in the
      differentiating cells through the all-trans-retinoic acid (ATRA)-mediated
      proteasome degradation pathway. Because HL60R cells that harbor a truncated
      ligand-dependent AF-2 domain of RARalpha do not demonstrate any changes in MAT1
      levels or CAK phosphorylation of RARalpha following ATRA stimuli, these
      biochemical changes appear to be mediated directly through RARalpha. These
      studies indicate that significant changes in MAT1 levels and CAK activities on
      RARalpha phosphorylation accompany the ATRA-induced G(1) arrest and
      differentiation activation, which provide new insights to explore the inversely
      coordinated P/D transition at G(1) exit.

PMID- 12213825
TI  - Dual regulation of phosphorylation and dephosphorylation of C/EBPbeta modulate
      its transcriptional activation and DNA binding in response to growth hormone.
AB  - The phosphorylation state of transcription factors is a critical determinant of
      their function. C/EBPbeta occurs in cells as the transcriptional activator liver
      enriched activating protein (LAP) and in the truncated form liver-enriched
      inhibitory protein (LIP) that inhibits transcription. Analysis of C/EBPbeta
      phosphorylation by isoelectric focusing (IEF) shows that LAP is present in
      multiple forms, each with a different degree of phosphorylation in 3T3-F442A
      fibroblasts. Growth hormone (GH) treatment induces a new band near the negative
      pole, consistent with GH-promoted dephosphorylation of LAP. In addition, bands
      near the positive pole are rapidly and transiently induced, suggesting that GH
      also stimulates phosphorylation at some site(s) on LAP. C/EBPbeta contains a
      highly conserved MAPK consensus site that corresponds to Thr(188) in murine (m)
      LAP and Thr(37) in mLIP. Immunoblotting with antiphosphopeptide antibodies
      specific for Thr(188/37) of C/EBPbeta (anti-P-C/EBPbeta) shows that GH rapidly
      and transiently promotes phosphorylation of mLAP and mLIP on the MAPK site. MEK
      inhibitors prevent this GH-promoted phosphorylation of LAP and LIP, suggesting
      that such phosphorylation depends on GH-activated MAPK signaling. Mutation of
      Thr(235) to Ala in the homologous MAPK site of human (h) LAP (hLAPT235A) inhibits
      transcription mediated by the c-fos promoter in response to GH, indicating that
      phosphorylation at the MAPK site is required for LAP to be transcriptionally
      active in the context of GH-stimulated activation of the c-fos promoter.
      Complexes bound to the c-fos C/EBP site transiently contain C/EBPbeta
      phosphorylated at the MAPK site. As phosphorylation subsides, the binding of less
      transcriptionally active forms of LAP increases, consistent with the transient
      nature of c-fos stimulation by GH and other growth factors. Thus, both
      phosphorylation and dephosphorylation of C/EBPbeta, in response to a single
      physiological stimulus such as GH, coordinately modulate the ability of C/EBPbeta
      to activate transcription by modulating its DNA binding activity and its
      transactivation capacity.

PMID- 12213826
TI  - Tapasin interacts with the membrane-spanning domains of both TAP subunits and
      enhances the structural stability of TAP1 x TAP2 Complexes.
AB  - The transporter associated with antigen processing (TAP) proteins are involved in
      transport of peptides from the cytosol into the endoplasmic reticulum. Two
      subunits, TAP1 and TAP2, are necessary and sufficient for peptide binding and
      peptide translocation across the endoplasmic reticulum membrane. TAP1 and TAP2
      contain an N-terminal hydrophobic membrane-spanning region and a C-terminal
      nucleotide binding domain. Tapasin is an endoplasmic reticulum resident protein
      that has been found associated with the TAP subunits and shown to increase
      expression levels of TAP. Here we investigated TAP-tapasin interactions and their
      effects on TAP function in insect cells. We show tapasin binding to both TAP1 and
      TAP2 and to the corresponding nucleotide binding domain-exchanged chimeras as
      well as to a truncated TAP1.TAP2 complex containing just the membrane-spanning
      regions of TAP1 and TAP2. However, tapasin interactions with either the truncated
      TAP construct containing just the nucleotide binding domain are not observed.
      Tapasin is not required for high affinity peptide binding to TAP1.TAP2 complexes,
      and in fact, the presence of tapasin slightly reduces the affinity of TAP
      complexes for peptides. However, at near physiological temperatures, both tapasin
      and nucleotides stabilize the peptide binding site of TAP1.TAP2 complexes against
      inactivation, and enhanced thermostability of both TAP subunits is observed in
      the presence of tapasin. The enhanced structural stability of TAP1.TAP2 complexes
      in the presence of tapasin might explain the observations that tapasin increases
      TAP protein expression levels in mammalian cells.

PMID- 12213827
TI  - Functional characterization of the 11 non-ATPase subunit proteins in the
      trypanosome 19 S proteasomal regulatory complex.
AB  - The ubiquitin-proteasome pathway is responsible for selective degradation of
      short-lived and dysfunctional proteins in eukaryotes. The recently demonstrated
      presence of a functional 26 S proteasome in Trypanosoma brucei led to the
      identification and isolation of genes encoding all 11 non-ATPase (Rpn) subunit
      proteins in the trypanosome 19 S regulatory complex. Using the technique of RNA
      interference, expression of individual RPN genes was disrupted in the procyclic
      form of T. brucei, resulting, in each case, in intracellular accumulation of
      polyubiquitinated protein, cell arrest at the G2/M phase, and eventual cell
      death. With the exception of Rpn10, depletion of individual Rpn proteins
      disrupted also trypanosome 19 S complex formation, with the complex virtually
      depleted in the cell lysate. This functional and structural essentiality of 10 of
      the 11 Rpn proteins in T. brucei differs significantly from that observed in
      other organisms. When Rpn10 was deficient in trypanosomes, a 19 S complex without
      Rpn10 was still formed, whereas cell growth was arrested. This structural
      dispensability but functional indispensability of Rpn10 may constitute another
      unique aspect of the proteasomes in T. brucei.

PMID- 12213829
TI  - SUR-dependent modulation of KATP channels by an N-terminal KIR6.2 peptide.
      Defining intersubunit gating interactions.
AB  - Ntp and Ctp, synthetic peptides based on the N- and C-terminal sequences of
      K(IR)6.0, respectively, were used to probe gating of K(IR)6.0/SUR K(ATP)
      channels. Micromolar Ntp dose-dependently increased the mean open channel
      probability in ligand-free solution (P(O(max))) and attenuated the ATP inhibition
      of K(IR)6.2/SUR1, but had no effect on homomeric K(IR)6.2 channels. Ntp (up to
      approximately 10(-4) m) did not affect significantly the mean open or "fast,"
      K(+) driving force-dependent, intraburst closed times, verifying that Ntp
      selectively modulates the ratio of mean burst to interburst times. Ctp and Rnp, a
      randomized Ntp, had no effect, indicating that the effects of Ntp are structure
      specific. Ntp opened K(IR)6.1/SUR1 channels normally silent in the absence of
      stimulatory Mg(-) nucleotide(s) and attenuated the coupling of high-affinity
      sulfonylurea binding with K(ATP) pore closure. These effects resemble those seen
      with N-terminal deletions (DeltaN) of K(IR)6.0, and application of Ntp to
      DeltaNK(ATP) channels decreased their P(O(max)) and apparent IC(50) for ATP in
      the absence of Mg(2+). The results are consistent with a competition between Ntp
      and the endogenous N terminus for a site of interaction on the cytoplasmic face
      of the channel or with partial replacement of the deleted N terminus by Ntp,
      respectively. The K(IR) N terminus and the TMD0-L0 segment of SUR1 are known to
      control the P(O(max)). The L0 linker has been reported to be required for
      glibenclamide binding, and DeltaNK(IR)6.2/SUR1 channels exhibit reduced labeling
      of K(IR) with (125)I-azidoglibenclamide, implying that the K(IR) N terminus and
      L0 of SUR1 are in proximity. We hypothesize that L0 interacts with the K(IR) N
      terminus in ligand-inhibited K(ATP) channels and put forward a model, based on
      the architecture of BtuCD, MsbA, and the KcsA channel, in which TMD0-L0 links the
      MDR-like core of SUR with the K(IR) pore.

PMID- 12213828
TI  - PIKfyve Kinase and SKD1 AAA ATPase define distinct endocytic compartments. Only
      PIKfyve expression inhibits the cell-vacoulating activity of Helicobacter pylori
      VacA toxin.
AB  - The mammalian phosphatidylinositol (PtdIns)- 5-P/PtdIns-3,5-P(2)-producing kinase
      PIKfyve and AAA ATPase SKD1, as their yeast counterparts, are implicated in the
      formation and function of multivesicular bodies/late endosomes. Point mutations
      inhibiting the enzyme activities convert PIKfyve and SKD1 into dominant-negative
      mutants (PIKfyve(K1831E) and SKD1(E235Q)), whose expression in cells of kidney
      origin induces a vacuolation phenotype. This phenotype closely resembles the
      changes in late endosomal-lysosomal morphology that occur following cell exposure
      to the vacuolating cytotoxin (VacA) from Helicobacter pylori. Here we have
      examined the possible functional relationship between PIKfyve and SKD1 as well as
      the role of these enzymes in the molecular mechanism of VacA-induced
      intracellular vacuolation. When co-expressed in COS cells, PIKfyve(WT) reduced
      SKD1(E235Q)dependent vacuole formation, whereas SKD1(WT) did not alter the
      vacuolation induced by PIKfyve(K1831E). In addition, SKD1(E235Q) disrupted the
      normal distribution of PIKfyve(WT). Expression of PIKfyve(WT) in COS and HEK293
      cells inhibited vacuolation induced by subsequent intoxication with VacA, and
      microinjection of the PIKfyve lipid product PtdIns-3,5-P(2) produced a similar
      inhibitory effect. In contrast, in COS cells expressing SKD1(WT), VacA induced
      the formation of characteristic vacuoles with an efficiency similar to that in
      the control cells. These observations demonstrate that, although PIKfyve and SKD1
      are functionally related, only PIKfyve regulates VacA action, and suggest that
      the inhibition of PIKfyve PtdIns-3,5-P(2)-producing activity is a key molecular
      event in VacA-induced cellular vacuolation.

PMID- 12213830
TI  - Isoform-dependent formation of heteromeric Ca2+ release channels (ryanodine
      receptors).
AB  - Three ryanodine receptor (RyR) isoforms, RyR1, RyR2, and RyR3, are expressed in
      mammalian tissues. It is unclear whether RyR isoforms are capable of forming
      heteromeric channels. To investigate their ability to form heteromeric channels,
      we co-expressed different RyR isoforms in HEK293 cells and examined their
      interactions biochemically and functionally. Immunoprecipitation studies revealed
      that RyR2 is able to interact physically with RyR3 and RyR1 in HEK293 cells and
      that RyR1 does not interact with RyR3. Co-expression of a ryanodine binding
      deficient mutant of RyR2, RyR2 (I4827T), with RyR3 (wt) restored [(3)H]ryanodine
      binding to the mutant. Interactions between RyR isoforms were further assessed by
      complementation analysis using mutants RyR2 (I4827T), RyR2 (E3987A), RyR3
      (I4732T), RyR3 (E3885A), and RyR1 (E4032A), all of which are deficient in
      caffeine response. Caffeine-induced Ca(2+) release was restored in HEK293 cells
      co-transfected with mutants RyR2 (I4827T) and RyR3 (E3885A), RyR2 (E3987A) and
      RyR3 (I4732T), or RyR2 (I4827T) and RyR1 (E4032A), but not with RyR1 (E4032A) and
      RyR3 (I4732T), indicating that mutants of RyR2 and RyR3, or RyR2 and RyR1, but
      not RyR1 and RyR3, are able to complement each other. Co-expression of RyR3 (wt)
      and a pore mutant of RyR2, RyR2 (G4824A), produced regulatable single channels
      with intermediate unitary conductances. These observations demonstrate that RyR2
      is capable of forming functional heteromeric channels with RyR3 and RyR1, whereas
      RyR1 is incapable of forming heteromeric channels with RyR3.

PMID- 12213831
TI  - Leptin gene expression in human preadipocytes is switched on by maturation
      induced demethylation of distinct CpGs in its proximal promoter.
AB  - The peptide hormone leptin plays a major role in the regulation of energy intake
      and expenditure and is predominantly expressed in mature adipocytes but not in
      preadipocytes. Using bisulfite genomic sequencing, we found that 32 CpGs,
      distributed within a 317-bp sequence of the proximal leptin promoter, were highly
      methylated in human preadipocytes (73.4% +/- 9.0%). During maturation toward
      terminally differentiated adipocytes, this promoter region was extremely
      demethylated (9.4% +/- 4.4%). CpG methylation-dependent transcriptional activity
      of the promoter fragment was determined in transfection experiments using a set
      of 5'-truncated mock-, HhaI-, and SssI-methylated promoter-reporter constructs.
      Whereas the methylated CpG within the CCAAT/enhancer-binding protein alpha
      recognition site down-regulated reporter expression, methylated CpGs proximal to
      the TATA motif and/or in a further upstream region abrogated promoter activity
      completely. These distinct promoter CpG sequences were found unmethylated in
      leptin-expressing mature adipocytes. As evidenced by electrophoretic mobility
      shift assays, nuclear protein complexes were specifically formed on methylated
      oligonucleotide probes corresponding to the dedicated promoter sequences,
      indicating that methyl-CpG binding proteins participate in transcriptional
      repression and regulation of the human leptin gene.

PMID- 12213832
TI  - Integrin activation takes shape.
AB  - Integrins are cell surface adhesion receptors that are essential for the
      development and function of multicellular animals. Here we summarize recent
      findings on the regulation of integrin affinity for ligand (activation), one
      mechanism by which cells modulate integrin function. The focus is on the
      structural basis of integrin activation, the role of the cytoplasmic domain in
      integrin affinity regulation, and potential mechanisms by which activation
      signals are propagated from integrin cytoplasmic domains to the extracellular
      ligand-binding domain.

PMID- 12213833
TI  - Enthoprotin: a novel clathrin-associated protein identified through subcellular
      proteomics.
AB  - Despite numerous advances in the identification of the molecular machinery for
      clathrin-mediated budding at the plasma membrane, the mechanistic details of this
      process remain incomplete. Moreover, relatively little is known regarding the
      regulation of clathrin-mediated budding at other membrane systems. To address
      these issues, we have utilized the powerful new approach of subcellular
      proteomics to identify novel proteins present on highly enriched clathrin-coated
      vesicles (CCVs). Among the ten novel proteins identified is the rat homologue of
      a predicted gene product from human, mouse, and Drosophila genomics projects,
      which we named enthoprotin. Enthoprotin is highly enriched on CCVs isolated from
      rat brain and liver extracts. In cells, enthoprotin demonstrates a punctate
      staining pattern that is concentrated in a perinuclear compartment where it
      colocalizes with clathrin and the clathrin adaptor protein (AP)1. Enthoprotin
      interacts with the clathrin adaptors AP1 and with Golgi-localized, gamma-ear
      containing, Arf-binding protein 2. Through its COOH-terminal domain, enthoprotin
      binds to the terminal domain of the clathrin heavy chain and stimulates clathrin
      assembly. These data suggest a role for enthoprotin in clathrin-mediated budding
      on internal membranes. Our study reveals the utility of proteomics in the
      identification of novel vesicle trafficking proteins.

PMID- 12213834
TI  - DNA replication is required for the checkpoint response to damaged DNA in Xenopus
      egg extracts.
AB  - Alkylating agents, such as methyl methanesulfonate (MMS), damage DNA and activate
      the DNA damage checkpoint. Although many of the checkpoint proteins that
      transduce damage signals have been identified and characterized, the mechanism
      that senses the damage and activates the checkpoint is not yet understood. To
      address this issue for alkylation damage, we have reconstituted the checkpoint
      response to MMS in Xenopus egg extracts. Using four different indicators for
      checkpoint activation (delay on entrance into mitosis, slowing of DNA
      replication, phosphorylation of the Chk1 protein, and physical association of the
      Rad17 checkpoint protein with damaged DNA), we report that MMS-induced checkpoint
      activation is dependent upon entrance into S phase. Additionally, we show that
      the replication of damaged double-stranded DNA, and not replication of damaged
      single-stranded DNA, is the molecular event that activates the checkpoint.
      Therefore, these data provide direct evidence that replication forks are an
      obligate intermediate in the activation of the DNA damage checkpoint.

PMID- 12213835
TI  - Drosophila EB1 is important for proper assembly, dynamics, and positioning of the
      mitotic spindle.
AB  - EB1 is an evolutionarily conserved protein that localizes to the plus ends of
      growing microtubules. In yeast, the EB1 homologue (BIM1) has been shown to
      modulate microtubule dynamics and link microtubules to the cortex, but the
      functions of metazoan EB1 proteins remain unknown. Using a novel preparation of
      the Drosophila S2 cell line that promotes cell attachment and spreading, we
      visualized dynamics of single microtubules in real time and found that depletion
      of EB1 by RNA-mediated inhibition (RNAi) in interphase cells causes a dramatic
      increase in nondynamic microtubules (neither growing nor shrinking), but does not
      alter overall microtubule organization. In contrast, several defects in
      microtubule organization are observed in RNAi-treated mitotic cells, including a
      drastic reduction in astral microtubules, malformed mitotic spindles, defocused
      spindle poles, and mispositioning of spindles away from the cell center. Similar
      phenotypes were observed in mitotic spindles of Drosophila embryos that were
      microinjected with anti-EB1 antibodies. In addition, live cell imaging of mitosis
      in Drosophila embryos reveals defective spindle elongation and chromosomal
      segregation during anaphase after antibody injection. Our results reveal crucial
      roles for EB1 in mitosis, which we postulate involves its ability to promote the
      growth and interactions of microtubules within the central spindle and at the
      cell cortex.

PMID- 12213836
TI  - The CeCDC-14 phosphatase is required for cytokinesis in the Caenorhabditis
      elegans embryo.
AB  - In all eukaryotic organisms, the physical separation of two nascent cells must be
      coordinated with chromosome segregation and mitotic exit. In Saccharomyces
      cerevisiae and Schizosaccharomyces pombe this coordination depends on a number of
      genes that cooperate in intricate regulatory pathways termed mitotic exit network
      and septum initiation network, respectively. Here we have explored the function
      of potentially homologous genes in a metazoan organism, Caenorhabditis elegans,
      using RNA-mediated interference. Of all the genes tested, only depletion of CeCDC
      14, the C. elegans homologue of the budding yeast dual-specificity phosphatase
      Cdc14p (Clp1/Flp1p in fission yeast), caused embryonic lethality. We show that
      CeCDC-14 is required for cytokinesis but may be dispensable for progression of
      the early embryonic cell cycles. In response to depletion of CeCDC-14, embryos
      fail to establish a central spindle, and several proteins normally found at this
      structure are mislocalized. CeCDC-14 itself localizes to the central spindle in
      anaphase and to the midbody in telophase. It colocalizes with the mitotic kinesin
      ZEN-4, and the two proteins depend on each other for correct localization. These
      findings identify the CDC14 phosphatase as an important regulator of central
      spindle formation and cytokinesis in a metazoan organism.

PMID- 12213837
TI  - Regulation of membrane fusion by the membrane-proximal coil of the t-SNARE during
      zippering of SNAREpins.
AB  - We utilize structurally targeted peptides to identify a "tC fusion switch"
      inherent to the coil domains of the neuronal t-SNARE that pairs with the cognate
      v-SNARE. The tC fusion switch is located in the membrane-proximal portion of the
      t-SNARE and controls the rate at which the helical bundle that forms the SNAREpin
      can zip up to drive bilayer fusion. When the fusion switch is "off" (the
      intrinsic state of the t-SNARE), zippering of the helices from their membrane
      distal ends is impeded and fusion is slow. When the tC fusion switch is "on,"
      fusion is much faster. The tC fusion switch can be thrown by a peptide that
      corresponds to the membrane-proximal half of the cognate v-SNARE, and binds
      reversibly to the cognate region of the t-SNARE. This structures the coil in the
      membrane-proximal domain of the t-SNARE and accelerates fusion, implying that the
      intrinsically unstable coil in that region is a natural impediment to the
      completion of zippering, and thus, fusion. Proteins that stabilize or destabilize
      one or the other state of the tC fusion switch would exert fine temporal control
      over the rate of fusion after SNAREs have already partly zippered up.

PMID- 12213838
TI  - Crumbs interacts with moesin and beta(Heavy)-spectrin in the apical membrane
      skeleton of Drosophila.
AB  - The apical transmembrane protein Crumbs is necessary for both cell polarization
      and the assembly of the zonula adherens (ZA) in Drosophila epithelia. The apical
      spectrin-based membrane skeleton (SBMS) is a protein network that is essential
      for epithelial morphogenesis and ZA integrity, and exhibits close colocalization
      with Crumbs and the ZA in fly epithelia. These observations suggest that Crumbs
      may stabilize the ZA by recruiting the SBMS to the junctional region. Consistent
      with this hypothesis, we report that Crumbs is necessary for the organization of
      the apical SBMS in embryos and Schneider 2 cells, whereas the localization of
      Crumbs is not affected in karst mutants that eliminate the apical SBMS. Our data
      indicate that it is specifically the 4.1 protein/ezrin/radixin/moesin (FERM)
      domain binding consensus, and in particular, an arginine at position 7 in the
      cytoplasmic tail of Crumbs that is essential to efficiently recruit both the
      apical SBMS and the FERM domain protein, DMoesin. Crumbs, Discs lost, betaHeavy
      spectrin, and DMoesin are all coimmunoprecipitated from embryos, confirming the
      existence of a multimolecular complex. We propose that Crumbs stabilizes the
      apical SBMS via DMoesin and actin, leading to reinforcement of the ZA and
      effectively coupling epithelial morphogenesis and cell polarity.

PMID- 12213839
TI  - N-cadherin-dependent cell-cell contact regulates Rho GTPases and beta-catenin
      localization in mouse C2C12 myoblasts.
AB  - N-cadherin, a member of the Ca(2+)-dependent cell-cell adhesion molecule family,
      plays an essential role in skeletal muscle cell differentiation. We show that
      inhibition of N-cadherin-dependent adhesion impairs the upregulation of the two
      cyclin-dependent kinase inhibitors p21 and p27, the expression of the muscle
      specific genes myogenin and troponin T, and C2C12 myoblast fusion. To determine
      the nature of N-cadherin-mediated signals involved in myogenesis, we investigated
      whether N-cadherin-dependent adhesion regulates the activity of Rac1, Cdc42Hs,
      and RhoA. N-cadherin-dependent adhesion decreases Rac1 and Cdc42Hs activity, and
      as a consequence, c-jun NH2-terminal kinase (JNK) MAPK activity but not that of
      the p38 MAPK pathway. On the other hand, N-cadherin-mediated adhesion increases
      RhoA activity and activates three skeletal muscle-specific promoters.
      Furthermore, RhoA activity is required for beta-catenin accumulation at cell-cell
      contact sites. We propose that cell-cell contacts formed via N-cadherin trigger
      signaling events that promote the commitment to myogenesis through the positive
      regulation of RhoA and negative regulation of Rac1, Cdc42Hs, and JNK activities.

PMID- 12213840
TI  - Clinical review 151: The role of parathyroid hormone in the pathogenesis of
      glucocorticoid-induced osteoporosis: a re-examination of the evidence.

PMID- 12213841
TI  - Clinical review 152: Postpartum thyroiditis.

PMID- 12213842
TI  - Consensus statement on 21-hydroxylase deficiency from the Lawson Wilkins
      Pediatric Endocrine Society and the European Society for Paediatric
      Endocrinology.

PMID- 12213843
TI  - Guidelines for acromegaly management.

PMID- 12213844
TI  - Optimizing the outcomes of adjuvant radioiodine therapy in differentiated thyroid
      carcinoma.

PMID- 12213846
TI  - Ablation of thyroid residues with 30 mCi (131)I: a comparison in thyroid cancer
      patients prepared with recombinant human TSH or thyroid hormone withdrawal.
AB  - The aim of the study was to assess whether stimulation by recombinant human TSH
      (rhTSH) may be used in patients with differentiated thyroid carcinoma for
      postsurgical ablation of thyroid remnants using a 30-mCi standard dose of (131)I
      during thyroid hormone therapy. The rate of ablation was prospectively compared
      in three groups of patients consecutively assigned to one of three treatment
      arms: in the first arm, patients (n = 50) were treated while hypothyroid (HYPO);
      in the second arm, patients (n = 42) were treated while HYPO and stimulated in
      addition with rhTSH (HYPO + rhTSH); in the third arm, patients (n = 70) were
      treated while euthyroid (EU) on thyroid hormone therapy and stimulated with rhTSH
      (EU + rhTSH). The outcome of thyroid ablation was assessed by conventional HYPO
      (131)I scan performed in HYPO state 6-10 months after ablation. Basal serum TSH
      was elevated in the HYPO and HYPO + rhTSH groups. In the EU + rhTSH group, basal
      serum TSH was 1.3 +/- 2.5 micro U/ml (range, <0.005-11.9 micro U/ml). After
      rhTSH, serum TSH significantly increased in the HYPO + rhTSH group and the EU +
      rhTSH group. Basal 24-h radioiodine thyroid bed uptake was 5.8 +/- 5.7% (range,
      0.2-21%) and 5.4 +/- 5.7% (range, 0.2-26%) in the HYPO and HYPO + rhTSH groups,
      respectively. In the HYPO + rhTSH group, mean 24-h thyroid bed uptake rose to 9.4
      +/- 9.5% (range, 0.2-46%) after rhTSH (P < 0.0001). The 24-h uptake after rhTSH
      in the EU + rhTSH group was 2.5 +/- 4.3% (range, 0.1-32%), significantly lower (P
      < 0.0001) than that found in the HYPO and HYPO + rhTSH groups. The rate of
      successful ablation was similar in the HYPO and HYPO + rhTSH groups (84% and
      78.5%, respectively). A significantly lower rate of ablation (54%) was achieved
      in the EU + rhTSH group. Mean initial dose rate (the radiation dose delivered
      during the first hour after treatment) was significantly lower in the EU + rhTSH
      group (10.7 +/- 12.6 Gy/h) compared with the HYPO + rhTSH group (48.5 +/- 43
      Gy/h) and the HYPO group (27.1 +/- 42.5 Gy/h). In conclusion, our study indicates
      that by using stimulation with rhTSH, a 30-mCi standard dose of radioiodine is
      not sufficient for a satisfactory thyroid ablation rate. Possible reasons for
      this failure may be the low 24-h radioiodine uptake, the low initial dose rate
      delivered to the residues, and the accelerated iodine clearance observed in EU
      patients. Possible alternatives for obtaining a satisfactory rate of thyroid
      ablation with rhTSH may consist of increasing the dose of radioiodine or using
      different protocols of rhTSH administration producing more prolonged thyroid
      cells stimulation.

PMID- 12213847
TI  - The etiology of thyroid dysgenesis-still an enigma after all these years.

PMID- 12213848
TI  - Discordance of monozygotic twins for thyroid dysgenesis: implications for
      screening and for molecular pathophysiology.
AB  - Since the advent of biochemical screening for congenital hypothyroidism, the
      majority of monozygotic twins reported with thyroid dysgenesis have been
      discordant, and most were missed on neonatal screening, presumably due to fetal
      blood mixing. We hypothesized that there may be bias leading to preferential
      reporting of discordant twins and/or of false negative screening results.
      Therefore, we performed a systematic search for twins in two congenital
      hypothyroidism screening centers, Quebec and Brussels, that use a primary TSH
      approach. In Quebec, 10 pairs of twins were identified, all discordant for
      congenital hypothyroidism due to thyroid dysgenesis (4 monozygotic and 4
      dizygotic pairs) and dyshormonogenesis (2 dizygotic pairs). The 6 pairs
      identified in the Brussels database were also all discordant for congenital
      hypothyroidism due to thyroid dysgenesis (1 monozygotic and 3 dizygotic pairs)
      and dyshormonogenesis (2 dizygotic pairs). The median increase in TSH between
      screening and diagnosis was 7-fold in the monozygotic twins vs. 2-fold in matched
      singletons (P = 0.02), suggesting fetal blood mixing between the twins. In
      summary, discordance for thyroid dysgenesis is the rule in monozygotic twins, and
      fetal blood mixing may result in delayed or missed diagnoses. We therefore
      conclude that 1) a second sample for congenital hypothyroidism screening at 14 d
      of age should be considered for all same-sex twins; and 2) thyroid dysgenesis
      generally results from epigenetic phenomena, early somatic mutations, or
      postzygotic stochastic events.

PMID- 12213849
TI  - Osteoprotegerin gene polymorphism and the risk of osteoporosis and vascular
      disease.

PMID- 12213850
TI  - Sequence variations in the osteoprotegerin gene promoter in patients with
      postmenopausal osteoporosis.
AB  - Osteoprotegerin (OPG) is a recently discovered member of the TNF receptor
      superfamily that acts as an important paracrine regulator of bone remodeling. OPG
      knockout mice develop severe osteoporosis, whereas administration of OPG can
      prevent ovariectomy-induced bone loss. These findings implicate a role for OPG in
      the development of osteoporosis. In the present study, we screened the OPG gene
      promoter for sequence variations and examined their association with bone mineral
      density (BMD) in 103 osteoporotic postmenopausal women. Single-strand
      conformation polymorphism analysis followed by DNA sequencing revealed a presence
      of four nucleotide substitutions: 209 G-->A, 245 T-->G, 889 C-->T, and 950 T-->C.
      The frequencies of genotypes were as follows: GG (89.3%), GA (10.7%) for 209 G-
      >A polymorphism; TT (89.3%), TG (10.7%) for 245 T-->G polymorphism; and TT
      (25.2%), TC (53.4%), CC (21.4%) for 950 T-->C polymorphism. Substitution 889 C-
      >T was found in only two patients. Statistically significant association of
      genotypes with BMD at the lumbar spine (P = 0.005) was observed for 209 G-->A and
      245 T-->G polymorphisms. Haplotype GATG was associated with lower BMD as compared
      with GGTT haplotype. Our results suggest that 209 G-->A and 245 T-->G
      polymorphisms in the OPG gene promoter may contribute to the genetic regulation
      of BMD.

PMID- 12213851
TI  - Polycystic ovary syndrome, insulin resistance, and molecular defects of insulin
      signaling.

PMID- 12213853
TI  - Decreased insulin receptor (IR) autophosphorylation in fibroblasts from patients
      with PCOS: effects of serine kinase inhibitors and IR activators.
AB  - Insulin resistance is characteristic of many patients with polycystic ovary
      syndrome (PCOS). Several studies have suggested that a decrease in insulin
      receptor (IR) autophosphorylation is a significant component of this resistance.
      In this study, we have used a highly sensitive ELISA to measure IR tyrosine
      phosphorylation in fibroblasts from patients with PCOS and healthy control women.
      After the stimulation of intact fibroblasts with insulin, IR tyrosine
      phosphorylation in cells from the PCOS patients was decreased by approximately
      40% when compared with controls. However, when IR were first immunocaptured from
      fibroblasts and then stimulated with insulin, neither basal nor insulin
      stimulated IR autophosphorylation was different between the two groups,
      suggesting that a factor independent of the IR was involved. To examine the role
      of increased serine kinase activity in decreased IR autophosphorylation in PCOS,
      fibroblasts from PCOS patients were pretreated with inhibitors of serine kinases
      before insulin stimulation. Pretreatment with H7, a nonspecific protein kinase
      inhibitor, completely reversed the decrease in insulin-stimulated IR
      autophosphorylation. Pretreatment with H89, an inhibitor of protein kinase A,
      partially reversed this function, whereas pretreatment with Go6983, an inhibitor
      of protein kinase C, was without effect. We next studied the effects of two small
      molecule activators of the IR tyrosine kinase: TLK16998 and Merck L7. Both
      TLK16998 and Merck L7 were able to reverse the impaired insulin-stimulated IR
      autophosphorylation. In summary, a factor(s) extrinsic to the IR cause impaired
      IR signaling in fibroblasts from patients with PCOS. Reversal of the impaired IR
      signaling by inhibitors of serine kinase activity suggests that serine kinase
      mediated pathways may be involved in the insulin resistance. Moreover, the
      observation that TLK16998 and Merck L7 improved IR tyrosine phosphorylation in
      fibroblasts from patients with PCOS suggests that specific pharmacological
      therapies might be developed to treat the insulin resistance in PCOS.

PMID- 12213854
TI  - Progressive onset of adrenal insufficiency and hypogonadism of pituitary origin
      caused by a complex genetic rearrangement within DAX-1.
AB  - DAX-1 [dosage-sensitive sex reversal, adrenal hypoplasia congenital (AHC)
      critical region on the X chromosome, gene 1] is a transcription factor expressed
      in the adrenal gland and at all levels of the gonadotrope axis. Inactivating
      mutations of DAX1 result in the X-linked form of AHC with associated
      hypogonadotropic hypogonadism. AHC usually reveals itself as adrenal failure in
      early infancy, although a wide range of phenotypic expression has been reported.
      We describe a patient who was diagnosed with adrenal failure at 6 wk of age, but
      who experienced recovery of adrenal function of several months' duration later in
      infancy. He subsequently failed to undergo puberty because of hypogonadotropic
      hypogonadism of pituitary origin, and he was also diagnosed with schizophrenia in
      early adulthood. Molecular genetic analyses revealed a complex rearrangement in
      DAX1, including a 2.2-kb deletion spanning the entire second exon and a small 27
      bp insertion. The putative protein encoded by this mutated gene is 429 amino
      acids long. The initial 389 residues probably correspond to the wild-type DAX-1
      sequence, whereas the last 40 amino acids are presumably completely unrelated,
      being transcribed from the intronic sequence adjacent to exon 1. In vitro
      functional analyses confirm the absence of repressor activity exerted by such
      mutant protein. These studies expand the genotypic and phenotypic spectrum of DAX
      1 insufficiency in humans.

PMID- 12213855
TI  - Familial malignant catecholamine-secreting paraganglioma with prolonged survival
      associated with mutation in the succinate dehydrogenase B gene.
AB  - Approximately 10% of catecholamine-secreting tumors are malignant, and 10% are
      familial. These tumors have been associated with several hereditary syndromes,
      including multiple endocrine neoplasia type 2, von Hippel-Lindau syndrome,
      neurofibromatosis type 1, and familial paraganglioma. Mutations in succinate
      dehydrogenase (SDH) subunit genes have been identified in some kindreds with
      catecholamine-secreting tumors. In 1972 at the Mayo Clinic, a metastatic
      catecholamine-secreting paraganglioma was diagnosed in a 32-yr-old man. In 1979,
      7 yr after the initial surgical treatment, a lytic metastasis to the left femur
      was found and was treated with local external radiotherapy. Locally metastatic
      abdominal catecholamine-secreting paragangliomas were diagnosed in the patient's
      27-yr-old son. Analyses of the VHL, RET, SDHD, and SDHC genes revealed no
      mutations. However, a missense point mutation was detected in the SDHB gene:
      c.725G-->A in exon 7, which alters a conserved arginine at amino acid position
      242 to a histidine (R242H). Sequencing of the SDHB gene in the tumors did not
      reveal any somatic mutations or loss of heterozygosity of the remaining allele.
      Thirty years after the initial diagnosis, the father is one of the longest living
      survivors of malignant catecholamine-secreting paraganglioma. Our findings
      indicate that mutations in SDHB may be associated with metastatic, yet clinically
      indolent, abdominal paraganglioma in some families.

PMID- 12213856
TI  - High reliability of neonatal screening for congenital adrenal hyperplasia in
      Switzerland.
AB  - Newborn screening for congenital adrenal hyperplasia (CAH) is justified by the
      sometimes difficult clinical diagnosis and the risks associated with missed
      diagnosis, particularly the life-threatening salt-wasting crisis. In Switzerland,
      nationwide screening for CAH by measuring 17-hydroxyprogesterone levels in dried
      blood spots was introduced in 1992. At the Zurich University Children's Hospital,
      50% of the population of Switzerland is screened. The aim of the study was to
      evaluate the efficiency of the Zurich screening program. Between January 1, 1993,
      and May 31, 2001, 333,221 newborns were screened for CAH. Thirty-one newborns had
      CAH (incidence, 1 in 10,749); 30 were detected through screening (sensitivity,
      97%). A recall for suspected CAH was performed in only 60 cases, corresponding to
      a very low recall rate (0.0018%). In 30 recalls CAH was confirmed (positive
      predictive value, 50%; specificity, 99.99%). Fifteen of 31 patients profited from
      screening, as CAH had not been recognized clinically. The timely availability of
      screening results made therapy possible within the first week of life in most
      cases and helped in preventing salt-wasting crisis in all patients. With a
      sensitivity of 97%, a specificity of 99.99%, and a positive predictive value of
      50%, the Zurich neonatal screening program for CAH can be considered highly
      reliable.

PMID- 12213857
TI  - Treatment of central precocious puberty by subcutaneous injections of leuprorelin
      3-month depot (11.25 mg).
AB  - Depot GnRH agonists are widely used for the treatment of precocious puberty.
      Leuprorelin 3-month depot is currently used in adults but has not been evaluated
      in children. We evaluated the efficacy of this new formulation (11.25 mg every 3
      months), for the suppression of gonadotropic activation and pubertal signs in
      children with central precocious puberty. We included 44 children (40 girls) with
      early-onset pubertal development in a 6-month open trial. The inclusion criteria
      were clinical pubertal development before the age of 8 (girls) or 10 (boys),
      advanced bone age, enlarged uterus (>36 mm), testosterone more than 1.7
      nmol/liter (boys), and pubertal response of LH to GnRH (peak >5 IU/liter). The
      principal criterion for efficacy assessment, GnRH-stimulated LH peak less than 3
      IU/liter, was met in 81 of 85 (95%) of the tests performed at months 3 and 6. The
      remaining four values were slightly above the threshold. The levels of sex
      steroids were also significantly reduced and clinical pubertal development was
      arrested. Plasma leuprorelin levels, measured every 30 d, were essentially stable
      after d 60. Local intolerance was noted after 10 of 86 injections (12%), and was
      mild in four cases, moderate in five cases, and severe in one. Among these 10
      events, 4 consisted in local pain at injection's site. In conclusion, leuprorelin
      3-month depot efficiently inhibits the gonadotropic axis in 95% of children with
      central precocious puberty studied for a 6-month period. This regimen allows the
      reduction of the number of yearly injections from 12 to 4.

PMID- 12213858
TI  - Raloxifene does not modify insulin sensitivity and glucose metabolism in
      postmenopausal women.
AB  - Insulin sensitivity (Si), glucose tolerance, and lipid metabolism were
      investigated in osteopenic postmenopausal women before and after 6 months of
      treatment with raloxifene (60 mg/d) or placebo. In a group of women (n = 34),
      glucose metabolism was evaluated by means of an oral glucose tolerance test (75
      g). In another group of women (n = 24), Si and peripheral glucose utilization not
      dependent on insulin were evaluated by means of a frequently sampled iv glucose
      tolerance test associated with the minimal model method. No metabolic
      modification was observed in women receiving placebo. Raloxifene did not
      significantly modify high density lipoprotein-cholesterol and triglycerides,
      whereas it significantly decreased low density lipoprotein (LDL) cholesterol
      (4.84 +/- 0.34 mmol/liter vs. 3.83 +/- 0.49 mmol/liter; P = 0.014) and LDL/high
      density lipoprotein cholesterol ratio (3.21 +/- 0.31 mmol/liter vs. 2.46 +/- 0.44
      mmol/liter; P = 0.012). Fasting levels and responses to the oral glucose
      tolerance test of glucose, insulin, C-peptide, and C-peptide/insulin were not
      modified by raloxifene. Similarly, raloxifene did not modify Si (4.22 +/- 4.1 vs.
      5.13 +/- 1.75), or insulin (0.025 +/- 0.003 vs. 0.019 +/- 0.002). The present
      data show that in osteopenic postmenopausal women raloxifene reduces LDL levels
      but does not modify insulin sensitivity and glucose metabolism.

PMID- 12213859
TI  - Survival analysis of 19 patients with toxic thyroid carcinoma.
AB  - Among patients with differentiated thyroid carcinoma (diffTCa), the rare
      hyperfunctioning or toxic TCa (ToxTCa) was diagnosed when scintigraphic hot
      thyroid areas were attributable only to diffTCa (diameter >1 cm by pathological
      examination) and/or total thyroidectomy failed to induce hypothyroidism. Of 924
      cases of all TCa (papillary diffTCa 47.3%, follicular diffTCa 44.2%, others
      8.5%), 19 had ToxTCa (2.1%, 15 of 19 follicular, 4 of 19 papillary, P = 0.008).
      These received a more intensive radioiodine therapy (average cumulated (131)I
      activities 21.8 vs. 15.2 GBq, P < 0.01). Five-year survival rates for ToxTCa (n =
      19, 56%) and diffTCa (n = 545, 94.5%) differed [hazard ratio 4.8, 95% confidence
      interval (CI) 2.8-8.1, P = 0.001]. However, the differences were attenuated by
      matching ToxTCa and diffTCa (n = 57, 5-yr survival rate 74%) for age, sex, and
      histopathologic type (hazard ratio 2.1, 95% CI 1.13-3.9, P = 0.02). Correcting
      statistically for M(1) against M(0) stage distribution resulted in a further
      reduction of the hazard ratio (hazard ratio 1.8, 95% CI 0.93-3.48, P = 0.08). An
      M(1) stage is an important prognostic factor in ToxTCa patients. Thus, ToxTCa,
      treated with higher activities of (131)I, has a survival prognosis close to that
      of matched diffTCa cases, both groups consisting mainly (79%) of follicular
      subtypes.

PMID- 12213860
TI  - Predictors of outcome of long-term GnRH therapy in men with idiopathic
      hypogonadotropic hypogonadism.
AB  - GnRH treatment is successful in inducing virilization and spermatogenesis in men
      with idiopathic hypogonadotropic hypogonadism (IHH). However, a small subset of
      IHH men, poorly characterized to date, fail to reach a normal testicular volume
      (TV) and produce sperm on this therapy. To determine predictors of outcome in
      terms of TV and sperm count, we studied 76 IHH men (38% with anosmia) undergoing
      GnRH therapy for 12-24 months. The population was stratified according to the
      baseline degree of prior pubertal development: absent (group 1, n = 52), partial
      (group 2, n = 18), or complete (adult onset HH; group 3, n = 6). Cryptorchidism
      was recorded in 40% of group 1, 5% of group 2, and none in group 3. Pulsatile
      GnRH therapy was initiated at 5-25 ng/kg per pulse sc and titrated to attain
      normal adult male testosterone (T) levels. LH, FSH, T, and inhibin B (I(B))
      levels were measured serially, and maximum sperm count was recorded. A
      longitudinal mixed effects model was used to determine predictors of final TV. LH
      (97%) and T (93%) levels were normalized in the majority of IHH men. Groups 2 and
      3 achieved a normal adult testicular size (92%), FSH (96%), I(B) levels (93%),
      and sperm in their ejaculate (100%). However, given their prior complete puberty
      and thus primed gonadotropes and testes, group 3 responded faster, normalizing
      androgen production by 2 months and completing spermatogenesis by 6 months. In
      contrast, group 1 failed to normalize TV (11 +/- 0.4 ml) and I(B) levels (92 +/-
      6 pg/ml) by 24 months, despite normalization of their FSH levels (11 +/- 2
      IU/liter). Similarly, sperm counts of group 1 plateaued well below the normal
      range (median of 3 x 10(6)/ml) with 18% remaining azoospermic. The independent
      predictors of outcome of long-term GnRH therapy were: 1) the presence of some
      prior pubertal development (positive predictor; group effect (beta) = 4.3; P =
      0.003); 2) a baseline I(B) less than 60 pg/ml (negative predictor; beta = -3.7; P
      = 0.009); and 3) prior cryptorchidism (negative predictor; beta = -1.8; P =
      0.05). Notably, anosmia was not an independent predictor of outcome when adjusted
      for other baseline variables. Our conclusions are: 1) pulsatile GnRH therapy in
      IHH men is very successful in inducing androgen production and spermatogenesis;
      2) normalization of the LH-Leydig cell-T axis is achieved more uniformly than the
      FSH-Sertoli cell-I(B) axis during GnRH therapy; and 3) favorable predictors for
      achieving an adult testicular size and consequently optimizing spermatogenesis
      are prior history of sexual maturation, a baseline I(B) greater than 60 pg/ml,
      and absence of cryptorchidism.

PMID- 12213861
TI  - Pituitary autoimmunity in patients with Sheehan's syndrome.
AB  - Postpartum hemorrhage (PPH) is a frequent complication of pregnancy in India.
      Sheehan's description of postpartum hypopituitarism promoted the belief that PPH
      leads to necrosis of the enlarged pituitary gland of pregnancy and
      hypopituitarism. However, slow clinical progression suggests factors other than
      ischemia in its pathogenesis. Tissue necrosis could release sequestered antigens,
      triggering autoimmunity of the pituitary and delayed hypopituitarism in Sheehan's
      syndrome. Twenty-six consecutive patients with postpartum hypopituitarism were
      studied, 19 with Sheehan's syndrome based on a history of PPH and hormone profile
      suggesting pituitary failure [mean (SD) age 32.7 +/- 6.4 yr, duration of illness
      5.5 +/- 3.1 yr], and seven patients with no history of PPH, categorized as
      "Other." Pituitary imaging and basal T(4), TSH, cortisol, LH, FSH, 17beta
      estradiol, and autoantibodies against pituitary (PitAb) and thyroid (TMA) were
      evaluated. Controls included 28 healthy females without prior conception (22 +/-
      5 yr) and 28 with prior conception (26 +/- 5 yr). Twelve of 19 (63.1%) patients
      with Sheehan's syndrome and one of seven in the Other group had PitAb against the
      49-kDa autoantigen; neuron-specific enolase. Four of 28 (14.2%) controls without
      prior conception and 5 of 28 (17.8%) controls with prior conception had PitAb
      positivity (P < 0.001 and <0.01 vs. Sheehan's syndrome, respectively). There was
      no significant difference in the mean serum hormone values and TMA positivity
      between patients with Sheehan's syndrome and the Other group as well as patients
      with or without PitAb positivity. Pituitary autoimmunity may play a role in the
      cause of hypopituitarism following PPH.

PMID- 12213862
TI  - Long-term safety and efficacy of depot long-acting somatostatin analogs for the
      treatment of acromegaly.
AB  - Depot somatostatin analogs are now increasingly being prescribed as adjuvant and
      primary therapy for the treatment of acromegaly. Previous studies have shown them
      to be both effective and safe, suppressing GH levels to less than 2 micro g/liter
      in 50-65% of cases and normalizing serum IGF-I levels in 65%. However, published
      data on their long-term efficacy and safety is scanty. We analyzed data from 22
      patients (16 female and 6 male) treated with Sandostatin LAR or Lanreotide for an
      average of 41 months (range 12-89). Three patients had previously been treated
      with surgery, two with radiotherapy, and seven with both. Ten patients had
      received primary medical therapy. Mean pretreatment GH levels were 13.1 +/- 3.4
      micro g/liter, and IGF-I levels were 592.9 +/- 53.9 micro g/liter. Results after
      12 months of therapy indicated reduction in GH (3.2 +/- 0.7 micro g/liter; P <
      0.0001) and IGF-I (321.9 +/- 33.9 micro g/liter; P < 0.001) concentrations, and
      this was sustained at latest follow-up. Using GH criteria (serum GH < 2 micro
      g/liter), 46% of subjects achieved a cure at 12 months, and 36% achieved a cure
      long-term. Fifty-two percent achieved normal IGF-I values at 12 months, and 67%
      long-term. Mean fasting and 2-h plasma glucose concentrations were similar at
      latest follow-up and at 12 months to baseline values. Three patients developed
      impaired glucose tolerance within 12 months of treatment, one going on to develop
      frank diabetes mellitus. However, glucose tolerance improved in five patients.
      Five patients developed gallstones while on treatment. In summary, this study
      reports the long-term efficacy of the depot somatostatin analogs as either
      adjuvant or primary therapy. Although overall glucose tolerance did not change,
      the development of impaired glucose tolerance in three patients at a time when GH
      levels were not changing highlights the ongoing need to monitor the long-term
      safety of these preparations.

PMID- 12213863
TI  - Effect of long-term hormone replacement therapy on atherosclerosis progression in
      postmenopausal women relates to functional apolipoprotein e genotype.
AB  - Apolipoprotein (apo)E gene epsilon4 allele carrier status modulates the responses
      of lipoprotein metabolism to hormone-replacement therapy (HRT). We investigated
      the effect of long-term HRT on the progression of atherosclerosis in
      postmenopausal women with or without apoE epsilon4 allele. One hundred forty-one
      nonsmoking postmenopausal women, 45-71 yr old, were divided into 3 groups based
      on the use of HRT. The HRT-EVP group (n = 61) used sequential estradiol valerate
      (EV) plus progestin (P), the HRT-EV group used EV alone (n = 40), and a control
      group had no HRT. Of these 141 women, 93 participated in a 5-yr follow-up study
      in 1998. In addition to serum lipid concentration and apoE genotype, the
      atherosclerosis severity score of the abdominal aorta and carotid arteries was
      determined by sonography. In apoE4-negative subjects, the progression of
      atherosclerosis severity score was significantly faster in control than in the
      HRT groups (genotype-by-time interaction P = 0.0026); whereas in apoE4-positive
      subjects, there were no significant differences in atherosclerosis severity score
      progression between the control and HRT groups. The effects of HRT on
      atherosclerosis progression in subjects with no apo epsilon4-allele seems to be
      especially beneficial, compared with controls with same phenotype status but
      without HRT. These results may help us to understand, in more detail, the benefit
      and possible risk of HRT on atherosclerotic diseases.

PMID- 12213864
TI  - Effectiveness of thyroid hormone suppressive therapy in benign solitary thyroid
      nodules: a meta-analysis.
AB  - The effectiveness of thyroid hormone suppressive therapy in reducing the volume
      of benign thyroid nodules is controversial. It is important to clarify this
      therapeutic effect of thyroid hormone, because its prolonged use needs to be
      carefully weighed against its potential deleterious effects in the skeletal and
      cardiovascular systems. To evaluate the best available evidence, we conducted a
      systematic review and meta-analysis of the randomized controlled trials that
      fulfill the following inclusion criteria: single thyroid nodules proven benign by
      fine needle aspiration, treatment, and follow-up of at least 6 months; documented
      suppression of TSH; measurement of thyroid nodule volume by ultrasound; and
      response to therapy defined as more than 50% volume reduction from baseline. Six
      randomized clinical trials published between 1987 and 1999, with 346 patients,
      were included in the meta-analysis. Ninety percent of the participants were
      female. Using a random effects model, the overall effect size showed a relative
      risk of 1.9 (95% confidence interval, 0.95-3.81) favoring a treatment effect. A
      sensitivity analysis showed significant changes in the results. Suppressive
      thyroid hormone therapy for longer than 6 months is associated with a trend
      toward a reduction of more than 50% in volume of benign thyroid nodules, without
      achieving statistical significance. The results are highly sensitive to changes
      in the statistical analysis, especially if the method used ignores heterogeneity
      among the effect sizes. More studies are needed before this therapy can be widely
      recommended.

PMID- 12213865
TI  - Cytotoxic effects of carboplatinum and epirubicin in the setting of an elevated
      serum thyrotropin for advanced poorly differentiated thyroid cancer.
AB  - Chemotherapy represents the only therapeutic option in most poorly differentiated
      thyroid carcinomas, although its effect is limited and short lasting. The aim of
      this study was to evaluate whether increasing the metabolic rate of thyroid
      cancer cells by TSH stimulation might result in higher response rate to
      chemotherapy. Fourteen patients with poorly differentiated thyroid carcinoma and
      nonfunctioning diffuse lung metastases detected at computed tomography scan,
      entered this study. A combination of carboplatinum and epirubicin was
      administered at 4- to 6-wk intervals for six courses. TSH stimulation was
      achieved by reduction of the daily dose of L-thyroxine resulting in mild
      hypothyroidism (eight patients) or by administration of recombinant human TSH
      (six patients). Two additional patients did not complete the therapeutic protocol
      due to severe hematological side effects. Results were evaluated by comparison of
      lung computed tomography scans before and after therapy. One patient had a
      complete remission. Five patients had partial remission, and seven patients had
      disease stabilization. One patient progressed to death. The overall rate of
      positive responses was 37% that rose to 81% when including patients with stable
      disease. Serum thyroglobulin after chemotherapy declined more than 50% in six
      patients, with respect to basal levels. Apparently, no difference in the response
      rate was observed between exogenous or endogenous TSH stimulation. At the time of
      this analysis, among the patients who completed the treatment courses, 9 of 14
      patients (64.3%) are still alive (median survival from start of chemotherapy = 21
      months, range: 15-34). Six of these patients did not show progression of lung
      disease, whereas regrowth of lung metastases was observed in three patients after
      19, 20, and 21 months from chemotherapy, respectively. Five patients died of
      their disease, including the one who had progression of lung disease during
      chemotherapy, three who died for brain or bone metastases, and one who died for
      refractory local tumor invasion. No progression of lung metastases was observed
      until death in these four patients. In conclusion, the response rate of poorly
      differentiated thyroid cancer to chemotherapy observed in this study was
      favorable and promising. TSH stimulation may have contributed to these results.

PMID- 12213866
TI  - Differences in adipose tissue metabolism between postmenopausal and
      perimenopausal women.
AB  - Changes in adipose tissue metabolism may contribute to the changes in body fat
      distribution seen during the menopause transition. We compared in vitro abdominal
      and gluteal sc adipose tissue metabolism [basal and stimulated lipolysis and
      activity of adipose tissue lipoprotein lipase (AT-LPL)] in postmenopausal and
      perimenopausal women (n = 12/group), matched for race, body mass index (29.5 +/-
      3.8 kg/m(2); mean +/- SD), and percentage body fat (42 +/- 6%). The
      postmenopausal women were older (54 +/- 3 vs. 48 +/- 3 yr; P < 0.01) and had
      higher FSH (55.5 +/- 26.4 vs. 16.6 +/- 22.5 IU/ml; P < 0.01) and lower estradiol
      (33.8 +/- 14.9 vs. 97.4 +/- 61.7 pmol/liter; P < 0.05) concentrations than the
      perimenopausal women. Despite similar fat cell size and beta-adrenergic receptor
      and postreceptor (dibutyryl-cAMP)-stimulated lipolysis, basal lipolysis was 77%
      lower in gluteal adipose cells from postmenopausal compared with perimenopausal
      women (P < 0.05). Within each group, AT-LPL activity in the gluteal region was
      significantly higher than in the abdominal region (P < 0.05). In addition, AT-LPL
      activity was significantly higher in the postmenopausal compared with
      perimenopausal women in both gluteal (4.9 +/- 3.6 vs. 2.0 +/- 1.4 nmol free fatty
      acid/g.min; P < 0.05) and abdominal (3.2 +/- 2.6 vs. 1.3 +/- 0.9 nmol free fatty
      acid/g.min; P < 0.05) adipose cells. The results of this study suggest that
      menopause status is associated with differences in adipose tissue metabolism in
      both the abdominal and gluteal fat depots. The lower lipolysis and higher AT-LPL
      activity in postmenopausal women may predispose them to gain body fat after
      menopause.

PMID- 12213867
TI  - Efficacy and safety of nateglinide in type 2 diabetic patients with modest
      fasting hyperglycemia.
AB  - Nateglinide is a fast-acting insulin secretion agent that specifically targets
      postprandial hyperglycemia in patients with type 2 diabetes. The recent reduction
      in the diagnostic criteria for diabetes and improved understanding of the
      importance of early insulin secretion served as the rationale for this
      multicenter, double-blind, randomized, parallel-group, 24-wk study performed in
      675 patients with type 2 diabetes but only moderately elevated fasting plasma
      glucose (FPG) (FPG = 7.0-8.3 mmol/liter) to assess the efficacy and safety of
      three fixed doses of nateglinide (30, 60, or 120 mg, with meals). A substudy of
      the effects on early insulin release and prandial glucose excursions following a
      standardized breakfast was performed in 127 subjects. Nateglinide was well
      tolerated and elicited a dose-dependent reduction of placebo-adjusted hemoglobin
      A(1c) (Delta = -0.26 to -0.39%) and FPG (Delta = -0.51 to -0.73 mmol/liter)
      accompanied by a dose-related increase in suspected hypoglycemic episodes.
      However, confirmed hypoglycemia occurred in only 5.3% of patients treated with
      the highest dose, compared with 1.2% in placebo-treated patients (P < 0.05).
      Nateglinide increased early insulin release and reduced prandial glucose
      excursions (P < 0.05 vs. placebo). In sum, nateglinide is a safe and effective
      therapeutic option for treatment of patients with mild to moderate fasting
      hyperglycemia.

PMID- 12213868
TI  - Abnormal bone mineral accrual in adolescent girls with anorexia nervosa.
AB  - Anorexia nervosa (AN) is increasingly common in adolescent girls and occurs at a
      time of peak bone mass formation. Osteopenia is common in adolescent girls with
      AN, and in a cross-sectional study, we have reported low bone formation markers
      in such girls. To determine the impact of chronic undernutrition on bone mineral
      accrual in contrast to healthy controls, we prospectively measured bone mineral
      density (BMD) and body composition by dual energy x-ray absorptiometry, bone
      metabolism markers, and nutritional and hormonal status at baseline, 6 months,
      and 12 months in 19 adolescent girls with AN (mean +/- SEM, 15.4 +/- 0.4 yr) and
      19 controls of comparable chronological and skeletal age. Overall, nutritional
      status in subjects with AN improved (mean percentage increase in body mass index
      from baseline, 9.2 +/- 1.9% and 15.2 +/- 2.6% at 6 and 12 months, respectively),
      with 11 subjects having recovered weight at 12 months. However, lumbar BMD at 12
      months (AN, 0.88 +/- 0.02 g/cm(2), vs. control, 0.98 +/- 0.03 g/cm(2); P = 0.008)
      remained significantly reduced in AN compared with controls, even in recovered
      subjects. This was due to significant increases in lumbar BMD in controls vs. no
      change in AN subjects over the year (0.003 +/- 0.001 g/cm(2).month vs. 0.000 +/-
      0.001 g/cm(2).month, respectively; P = 0.04). The most significant determinant of
      change in lumbar BMD at 12 months was change in lean body mass in both AN (r =
      0.62; P = 0.008) and control (r = 0.80; P = 0.0006) groups. There were
      significant increases in surrogate markers of bone turnover in subjects with AN
      compared with controls as assessed by osteocalcin (AN, 0.9 +/- 0.4 micro
      g/liter.month, vs. control, -1.1 +/- 0.4 micro g/liter.month; P = 0.0007), bone
      specific alkaline phosphatase (AN, 0.6 +/- 0.5 U/liter.month, vs. control, -1.5
      +/- 0.4 U/liter.month; P = 0.002), deoxypyridinoline [AN, 0.1 +/- 0.1 nmol/mmol
      creatinine (cr).month, vs. control, -0.4 +/- 0.1 nmol/mmol cr.month; P = 0.005],
      and N-telopeptide (AN, 4 +/- 4 nmol BCE/mmol cr/month, vs. control, -9 +/- 4 nmol
      BCE/mmol cr/month; P = 0.01). Changes in IGF-I levels over the year were highly
      correlated with changes in bone turnover over the same period in AN (osteocalcin,
      r = 0.77; P = 0.001; deoxypyridinoline, r = 0.66; P = 0.01). A rise in N
      telopeptide over the year was correlated with an increase in all bone mineral
      measures, including lumbar bone mineral content (r = 0.58; P = 0.03) and BMD (r =
      0.53; P = 0.05) and total bone mineral content (r = 0.69; P = 0.006) and BMD (r =
      0.69; P = 0.006) in the AN group. Therefore, despite recovery over 1 yr, poor
      bone mineral accrual persists in adolescent girls with AN in contrast to rapid
      bone accrual in healthy girls. Normalization of bone turnover markers occurs in
      association with nutritional recovery and an increase in the nutritionally
      dependent bone trophic factor IGF-I. A rise in bone turnover markers may be an
      early indicator of increase in BMD in recovering girls with AN.

PMID- 12213869
TI  - The effect of raloxifene on glyco-insulinemic homeostasis in healthy
      postmenopausal women: a randomized placebo-controlled study.
AB  - The effect of raloxifene, a selective estrogen receptor modulator recently
      approved as a therapeutic agent for menopause, on glyco-insulinemic metabolism
      was investigated in 40 healthy postmenopausal women. At the baseline and after 12
      wk of raloxifene (60 mg/d) or placebo administration, all aspects of glucose
      metabolism were evaluated in each subject using both an oral glucose tolerance
      test (OGTT; 75 g) and a hyperinsulinemic euglycemic clamp to assess peripheral
      insulin sensitivity. Glucose, insulin, and C-peptide, measured in fasting
      conditions, as well as glucose and insulin responses to OGTT [expressed as area
      under curve (AUC)] were not modified by raloxifene, whereas C-peptide-AUC
      increased significantly (P < 0.05). Furthermore, a trend toward an improvement of
      peripheral insulin sensitivity and hepatic clearance of the hormone (fractional
      hepatic insulin extraction) was observed in the raloxifene-treated women with
      respect to the control patients. When the subjects were studied in relation to
      their insulin secretion in response to the glucose load, the patients, classified
      as hyperinsulinemic, showed the most significant response to the raloxifene
      treatment. In these women, the selective estrogen receptor modulator was able to
      induce a significant reduction of insulin circulating plasma values (P < 0.01)
      through both an increase of fractional hepatic insulin extraction (P < 0.01) and
      an improvement of the peripheral insulin sensitivity (P < 0.05). On the contrary,
      no net change of insulin dynamics was observed in normoinsulinemic and placebo
      treated women. The present data indicate that raloxifene does not negatively
      influence glyco-insulinemic metabolism in unselected postmenopausal women and may
      indeed improve the excessive insulin responsiveness to OGTT in a selected
      population of hyperinsulinemic postmenopausal women.

PMID- 12213870
TI  - Short-term suppression of GH and IGF-I levels improves gonadal function and sperm
      parameters in men with acromegaly.
AB  - Experimental data support a role for GH and IGF-I in the reproductive process in
      humans, but the effect of chronic GH excess on gonadal and reproductive function
      in men has been never investigated. To understand the effects of short-term GH
      and IGF-I suppression on the gonadal axis and seminal fluid characteristics in
      men with acromegaly, we evaluated 35 patients (age 27-59 yr) with active disease
      and 35 age-matched healthy controls. Gonadal hormones and seminal fluid analysis
      were evaluated before and 6 months after surgery or lanreotide (LAN) (60
      mg/month). At study entry, FSH, testosterone (T), and dihydrotestosterone (DHT)
      (P < 0.0001) levels, seminal volume, sperm count, total motility and forward
      progression, normal morphology, and vitality were significantly lower in patients
      with acromegaly than in controls. After 6 months, 22 patients achieved disease
      control after surgery (n = 11) or LAN (n = 11), whereas 13 had uncontrolled
      disease. Serum T and DHT levels and sperm number significantly increased in all
      groups. FSH and LH levels and total motility increased only in patients achieving
      disease control. Posttreatment IGF-I levels significantly correlated with total
      motility (r = -0.45; P = 0.006). In conclusion, short-term GH and IGF-I
      suppression after surgery or LAN significantly increased T and DHT levels and
      improved sperm number and motility in acromegalic men.

PMID- 12213871
TI  - A polymorphism in the human agouti-related protein is associated with late-onset
      obesity.
AB  - The mouse agouti-related protein (AGRP) is a powerful appetite effector that
      results in hyperphagia and the development of obesity when administered
      intracerebroventricularly or when overexpressed in transgenic mice. Animal
      studies have also shown that exogenous administration of AGRP predisposes toward
      hedonic intake of high fat and high sucrose diets. The human ortholog (hAGRP)
      maps on chromosome 16q22 and has similar physiological properties, as tested in
      animal models. A polymorphism was identified in the third exon of hAGRP, c.199G-
      >A, that resulted in a nonconservative amino acid substitution, Ala(67)Thr.
      Computational analysis of the protein showed significant differences in the coils
      of the two polymorphic isoforms of the protein. Human studies showed no genotype
      effects in individuals with a mean age of 25 yr. However, the G/G genotype was
      significantly associated with fatness and abdominal adiposity in the parental
      population with a mean age of 53 yr. The c.199G-->A polymorphism in hAGRP could,
      therefore, play a role in the development of human obesity in an age-dependent
      fashion.

PMID- 12213872
TI  - Differential effects of adiposity on peroxisomal proliferator-activated receptor
      gamma1 and gamma2 messenger ribonucleic acid expression in human adipocytes.
AB  - Both genetic and pharmacological studies raise the possibility that a primary
      increase in the amount or activity of peroxisomal proliferator-activated receptor
      gamma (PPARgamma) in adipocytes could play a role in common types of human
      obesity. Using real-time RT-PCR assays we examined the relationship between body
      mass index (BMI) and PPARgamma isoform expression in freshly isolated human
      adipocytes. There were no consistent differences in the expression of either
      PPARgamma1 mRNA or PPARgamma2 mRNA between omental and sc adipocytes. In a group
      of 17 subjects (BMI range, 17-34 kg/m(2)) there was a strong and highly
      significant inverse correlation (r = -0.68; P < 0.005) between PPARgamma1 mRNA
      expression in adipocytes and BMI, whereas no significant relationship was
      apparent for PPARgamma2. In an independent study PPARgamma1 mRNA levels were
      decreased (1.1 +/- 0.1 vs. 3.7 +/- 0.8 arbitrary units; P < 0.01) in adipocytes
      from morbidly obese (BMI, 50.6 +/- 14.1 kg/m(2)) vs. lean (BMI, 21.1 +/- 1.0
      kg/m(2)) subjects. In contrast, there was a significant increase in the
      expression of PPARgamma2 mRNA levels between the morbidly obese and lean groups
      (1.7 +/- 0.2 vs. 1.1 +/- 0.2 arbitrary units; P < 0.05). Treatment of isolated
      human adipocytes with TNFalpha resulted in a significant decrease in both
      PPARgamma1 and PPARgamma2 mRNA levels [40.6 +/- 5.5% relative to control (P =
      0.01) and 60.9 +/- 24.8% (P = 0.02) respectively]. The strong inverse
      relationship between BMI and PPARgamma1 expression in human adipocytes is
      striking and may represent part of an autoregulatory mechanism restraining the
      expansion of individual adipocytes in states of positive energy balance. On the
      other hand, the increase in PPARgamma2 observed in adipocytes of morbidly obese
      individuals suggests a potential pathogenic effect of this isoform in promoting
      fat acquisition. Although an autocrine effect of the enhanced TNFalpha secretion
      seen with increasing obesity might play a role in the changes in PPARgamma1, this
      would not provide an explanation for the different relationship of PPARgamma2 to
      adiposity. The significance of the divergent effect of human adiposity on the two
      isoforms will require a greater understanding of the differential properties of
      the two isoforms and of the differences in the functions of their respective
      regulatory elements.

PMID- 12213873
TI  - High prevalence of a novel mutation (2268 insT) of the thyroid peroxidase gene in
      Taiwanese patients with total iodide organification defect, and evidence for a
      founder effect.
AB  - The mutation of the thyroid peroxidase (TPO) gene that causes the total iodide
      organification defect (TIOD) is a common and severe condition leading to
      dyshormonogenesis of the thyroid gland in Caucasians. However, the role of TIOD
      in Chinese patients with thyroid dyshormonogenesis is unknown. In this study we
      followed 16 patients from 16 unrelated families in Taiwan and performed
      perchlorate discharge examination. Seven patients had TIOD and 2 had the partial
      iodine organification defect (PIOD) among the 16 families. These 9 patients
      underwent screening in search of TPO gene mutations. Three new mutations (2268
      insT, 2243 delT, and G157C) were detected in the 7 patients with TIOD, whereas no
      mutation in the TPO gene was found in the 2 patients with PIOD. The 2268 insT
      mutation was noted to be the most common among these TIOD patients (12 of 14
      studied alleles, 86%). With 3 intragenic polymorphic markers, we found that the
      alleles carrying the 2268 insT mutation in Taiwan Chinese TIOD patients were
      tightly linked to a specific haplotype. The allele frequencies of this haplotype
      in the 8 patients with homozygous 2268 insT (5 unrelated families, 10 studied
      alleles) and in 49 normal individuals (98 studied alleles) were 1.00 and 0.02,
      respectively (P < 0.0001). This indicates that this common novel mutation among
      Taiwanese patients with TIOD is due to a founder effect.

PMID- 12213874
TI  - Human placental vascular development: vasculogenic and angiogenic (branching and
      nonbranching) transformation is regulated by vascular endothelial growth factor
      A, angiopoietin-1, and angiopoietin-2.
AB  - During placental development, vessel formation occurs initially by vasculogenesis
      and subsequently by branching and nonbranching angiogenesis. We investigated
      vascular endothelial growth factor (VEGF)-A, angiopoietin (Ang)-1 and -2
      transcript profiles, and the protein products that they encode in placentas from
      normotensive pregnancies throughout pregnancy. In addition, we compared these
      genes in placentas from normotensive women and those with preeclampsia during the
      third trimester. Quantitative real-time PCR analysis demonstrated that VEGF-A and
      Ang1 mRNA increased in a linear pattern by 2.5 (not significant) and 2.8%/wk (P =
      0.034), respectively, whereas Ang2 decreased logarithmically by 3.5%/wk (P =
      0.0003). Ang2 mRNA was 400- and 100-fold higher than Ang1 and VEGF-A,
      respectively, in the first trimester and declined to 20-fold and 7-fold in the
      third. Ang2 protein (ELISA) decreased by 4.7%/wk (P = 0.0001), whereas Ang1 and
      VEGF-A were undetectable. In preeclampsia compared with normotensive pregnancy,
      only VEGF-A mRNA increased significantly, by 3-fold (P = 0.006). This increase
      may be related to low oxygen tension, as VEGF-A is up-regulated by hypoxia. In
      situ hybridization and immunohistochemical studies revealed that VEGF-A was
      localized in cyto- and syncytiotrophoblast and perivascular cells, whereas Ang1
      and Ang2 were only in syncytiotrophoblast and perivascular cells in the immature
      intermediate villi during the first and second trimesters, and mature
      intermediate and terminal villi during the third trimester. These data suggest
      that these molecules may play important roles in placental biology and chorionic
      villus vascular development and remodeling in an autocrine/paracrine manner. The
      tight correlation between Ang2 mRNA and protein indicates that regulation of
      placental vascular development occurs at the transcriptional, and not
      translational, level.

PMID- 12213875
TI  - Low amplitude and disorderly spontaneous growth hormone release in obese women
      with or without polycystic ovary syndrome.
AB  - Obesity is associated with considerably reduced plasma GH concentrations, which
      may contribute to anovulation in (obese) women with polycystic ovary disease
      (PCOS). This clinical investigation was undertaken to establish whether the GH
      release process is deranged in obese women with PCOS and, if so, whether the
      observed anomalies are features of the syndrome or a sequel of body fat
      accretion. To this end we sampled 24-h plasma GH concentration profiles at 10-min
      intervals in 15 obese PCOS patients [mean age, 29 yr (range, 20-38); percent body
      fat, 47 +/- 5.2%], 15 equally obese controls with regular menstrual cycles [age,
      34 yr (range, 20-44); percent body fat, 48 +/- 4.9%], and 15 healthy age-matched
      lean controls [age, 34 yr (range, 21-45); percent body fat, 29 +/- 9.0%].
      Compared with lean controls, obese PCOS patients exhibited a greater than 60%
      reduction in basal and a greater than 75% reduction in pulsatile and total daily
      GH secretion due to a 2.7-fold attenuation of burst mass and a lesser (1.4-fold)
      slowing of GH pulse frequency. The mean +/- SEM number of statistically
      significant GH peaks was 13.9 +/- 1.2/24 h, the endogenous GH half-life was 14.1
      +/- 0.4 min, basal GH secretion was 5.0 +/- 0.7 mU/liter.24 h, and total
      secretion was 61.4 +/- 9.6 mU/liter.24 h in obese women with PCOS. None of these
      parameters differed from those in the body mass index-matched controls. The
      approximate entropy ratio was significantly increased in obese women (both PCOS
      and controls), indicating greater irregularity of the GH release process. Total
      GH secretion in patients and the two control groups correlated strongly and
      negatively with percent body fat (r = -0.775; P < 10(-8)). Serum concentrations
      of IGF-I and IGF-binding protein-3 were higher in patients with PCOS than in
      obese controls (P = 0.03 and P = 0.02, respectively), but the IGF-1/IGF-binding
      protein-3 ratio was equivalent in all three study groups. In conclusion, the
      profoundly reduced and irregular GH release in obese women with PCOS appears to
      be a corollary of body fat accretion and not of the syndrome per se.

PMID- 12213876
TI  - Maternal obesity is associated with dysregulation of metabolic, vascular, and
      inflammatory pathways.
AB  - Obesity is increasing in prevalence worldwide and in all age groups. In
      nonpregnant individuals, obesity is associated with dyslipidemia;
      hyperinsulinemia; vascular dysfunction; and, more recently, low-grade chronic
      inflammation. However, whether such effects are sustained during pregnancy has
      been sparsely investigated but is important to establish, given the association
      of maternal obesity with numerous adverse metabolic and vascular consequences. We
      consecutively recruited 47 healthy women in the third trimester of pregnancy and
      divided the participants into 2 groups, lean [n = 24; median body mass index
      (BMI), 22.1 kg/m(2)] and obese (n = 23; median BMI, 31.0 kg/m(2)) around the
      median first trimester BMI. The age, parity, and smoking history were comparable
      in both groups. A detailed panel of metabolic and inflammatory parameters was
      measured and an in vivo assessment of endothelial-dependent and -independent
      microvascular function made using laser doppler imaging. Although low-density
      lipoprotein cholesterol and glycosylated hemoglobin were similar, fasting
      triglyceride concentrations were higher [2.70 (interquartile range, 2.3-3.21) vs.
      2.20 (IQ range, 2.0-2.6) mmol/liter, P = 0.02] and high-density lipoprotein
      concentrations were lower [1.55 (IQ range, 1.1-1.7) vs. 1.72 (IQ range, 1.4-2.0)
      mmol/liter, P = 0.02] in the obese group. Leptin [55.6 (range, 45-64.4) ng/ml vs.
      23.8 (range, 13.2-35.2) ng/ml, P < 0.0001] and fasting insulin [14.5 (range, 11.4
      27.3) vs. 6.5 (range, 4.6-9.7) mU/liter, P < 0.0001] levels were more than
      double. Similarly, levels of inflammatory parameters, IL-6 [3.15 (range, 2.4-3.5)
      vs. 2.1 (range, 1.73-2.85) pg/ml, P = 0.003], and sensitive C-reactive protein
      [4.45 (range, 2.9-6.6) vs. 2.25 (range, 0.92-3.65) mg/ml, P = 0.0015] were also
      substantially elevated. Both endothelial-dependent and -independent vasodilatory
      responses were significantly reduced in the obese group (P = 0.0003 and P = 0.02,
      respectively, ANOVA) and systolic blood pressure was higher (P = 0.01). Metabolic
      factors, C-reactive protein (r = 0.289, P = 0.049), and insulin (r = 0.339, P =
      0.02) were related inversely to endothelial-dependent function. These
      comprehensive data demonstrate that, as in nonpregnant obese individuals, obesity
      in pregnancy is associated not only with marked hyperinsulinemia (without
      necessarily glucose dysregulation) and dyslipidemia but also impaired endothelial
      function, higher blood pressure, and inflammatory up-regulation. Such a spectrum
      of risk factors may contribute to maternal complications in obese women and, as a
      result, influence fetal programming of adult vascular disease. Clearly, these
      data provide further rationale to examine the potential benefits of preconceptual
      weight loss and antenatal exercise.

PMID- 12213878
TI  - Vascular endothelial growth factor, its receptor KDR/Flk-1, and pituitary tumor
      transforming gene in pituitary tumors.
AB  - Pituitary tumorigenesis is a poorly understood process involving dysregulation of
      the cell cycle, proliferation, and angiogenesis. The novel securin pituitary
      tumor transforming gene (PTTG) disrupts cell division and stimulates fibroblast
      growth factor (FGF)-2-mediated angiogenesis. We investigated expression of the
      angiogenic vascular endothelial growth factor (VEGF) and its receptor KDR/Flk-1
      in 103 human pituitary tumors, and we assessed functional relationships between
      these genes in vitro. Nonfunctioning tumors (n = 81) demonstrated markedly raised
      VEGF mRNA (3.2-fold, P < 0.05) and protein concentrations, compared with normal
      pituitaries (n = 10). KDR was also highly induced in nonfunctioning tumors (14
      fold, P < 0.001, n = 78) as well as in the whole cohort of pituitary tumors,
      compared with normal pituitary samples (14-fold, P < 0.0001, n = 100). In vitro,
      PTTG induced VEGF, but not KDR, expression in fetal neuronal NT2 cells (2.7-fold,
      P < 0.001, n = 8), MCF-7 breast carcinoma cells (1.9-fold, P = 0.03, n = 10), and
      choriocarcinoma JEG-3 cells (P = 0.0002, n = 8). A mutated PTTG construct that
      cannot be phosphorylated showed identical VEGF up-regulation (2.9-fold, P <
      0.001, n = 8) in NT2 cells, compared with wild-type PTTG, but a further mutated
      construct with abrogation of the key protein:protein interaction domain of PTTG
      resulted in a significant reduction in VEGF stimulation, compared with wild-type
      (0.37-fold reduction, P < 0.001, n = 8). FGF-2 findings mirrored those of VEGF,
      although antibody depletion of secreted FGF-2 in the cell medium failed to
      influence VEGF up-regulation by PTTG. Overall, our findings implicate altered
      VEGF and KDR signaling in pituitary tumorigenesis, and we propose that PTTG
      stimulation of FGF-2 and VEGF expression in the presence of up-regulated growth
      factor receptors may account for angiogenic growth and progression of human
      pituitary tumors.

PMID- 12213879
TI  - Altered responsiveness of the hypothalamus-pituitary-adrenal axis and the
      sympathetic adrenomedullary system to stress in patients with atopic dermatitis.
AB  - A growing number of animal data strongly suggest that a hyporeactive hypothalamus
      pituitary adrenal (HPA) axis may be pathologically significant by increasing the
      susceptibility to chronic inflammation. Following this line of evidence, the
      specific goal of the present study was to investigate the HPA axis in patients
      with atopic dermatitis (AD), a chronic allergic inflammatory disease. In
      addition, the sympathetic adrenomedullary (SAM) system as a second potent
      immunoregulatory and anti-inflammatory stress-response system has been examined.
      AD patients (n = 36) and nonatopic control subjects (n = 37) were exposed to a
      standardized laboratory stressor consisting of a free speech and mental
      arithmetic task in front of an audience. Cortisol, ACTH, and catecholamine
      concentrations were assessed before and after the stressor. To investigate
      feedback sensitivity of the HPA axis, a low dose (0.5 mg) dexamethasone
      suppression test was also performed. AD patients showed significantly attenuated
      cortisol and ACTH responses to the stressor, whereas catecholamine levels were
      significantly elevated in atopic patients. No difference between the experimental
      groups was found in basal cortisol and ACTH concentrations, whereas basal
      catecholamine levels were significantly elevated. Analysis of cortisol levels
      after dexamethasone treatment suggested an intact feedback sensitivity in AD
      sufferers at the pituitary level. The present findings suggest that patients with
      AD demonstrate a blunted HPA axis responsiveness with a concurrent overreactivity
      of the SAM system to psychosocial stress. Considering the important
      immunoregulatory role of the HPA axis and the SAM system, especially under
      stressful conditions, an aberrant responsiveness of these neuroendocrine systems
      may increase the susceptibility to (allergic) inflammation and may be one
      psychobiological mechanism of stress-related aggravation of the disease.

PMID- 12213880
TI  - The intrauterine environment is a strong determinant of glucose tolerance during
      the neonatal period, even in prematurity.
AB  - The aim of this study was to determine the contribution of birth weight and
      gestational age to glucose tolerance in premature neonates. The study group
      consisted of 100 premature and/or small-for-gestational age infants.
      Anthropometric measurements were performed both at birth and at the time of a
      standardized milk feed carried out at 19.6 +/- 12.1 d (range, 1-65 d) after
      birth. Fasting and postprandial glucose and insulin levels were measured. Birth
      weight, as a proxy mirror of the intrauterine environment, was found to influence
      the glucose concentration following a standardized milk feed (beta = -0.46; P =
      0.01 for birth weight z-score with 60-min glucose level), whereas gestational age
      did not. Small-for-gestational age neonates had higher 60-min insulin levels than
      appropriate-for-gestational age neonates (115.4 +/- 9.5 vs. 68.4 +/- 14.2; P <
      0.05) despite similar glucose levels. Neonates born of mothers who were on
      antihypertensive treatment were smaller and had a higher insulin secretory
      response than neonates from normotensive mothers. Postnatal growth velocity
      (kilograms per day) correlated with birth weight (beta = -0.65; P < 0.0001) and
      insulin resistance (beta = -0.31; P = 0.0004), independently of each other. This
      study shows that glucose tolerance of the neonate is determined by weight
      attained at birth irrespective of gestational age and that maternal blood
      pressure may influence insulin sensitivity of the newborn. Furthermore, catch-up
      growth in neonates is determined by birth weight and insulin sensitivity.

PMID- 12213882
TI  - Expression of activin/inhibin receptor and binding protein genes and regulation
      of activin/inhibin peptide secretion in human adrenocortical cells.
AB  - Activins and inhibins are glycoprotein hormones produced mainly in gonads but
      also in other organs. They are believed to be important para/autocrine regulators
      of various cell functions. We investigated activin/inhibin receptor and binding
      protein gene expression and the regulation of activin/inhibin secretion in human
      adrenal cells. RT-PCR revealed inhibin/activin alpha-, betaA/B-subunit,
      follistatin, activin type I/II receptor, and inhibin receptor (betaglycan and
      inhibin-binding protein) mRNA expression in fetal and adult adrenals and cultured
      adrenocortical cells. Cultured cells secreted activin A and inhibin A/B as
      determined by specific ELISAs. ACTH stimulated inhibin A/B secretion in fetal
      (1.8- and 1.8-fold of control, respectively) and in adult cells (3.4- and 1.7
      fold of control, respectively) without significant effect on activin A. 8
      bromoadenosine cAMP (protein kinase A activator) increased activin A and inhibin
      A/B secretion in the human adrenocortical NCI-H295R cell line (32-, 17-, and 3
      fold of control, respectively). 12-O-tetradecanoyl phorbol-13-acetate (protein
      kinase C activator) stimulated both activin A and inhibin A secretion (764- and
      32-fold of control, respectively), and activin treatment increased inhibin B
      secretion in these cells (25-fold of control). In conclusion, human
      adrenocortical cells produce dimeric activins and inhibins. ACTH stimulates
      inhibin secretion and decreases activin/inhibin secretion ratio, probably via the
      protein kinase A signal transduction pathway. This, together with the
      adrenocortical activin/ inhibin receptor and binding protein expression, suggests
      a physiological role for activins and inhibins in the human adrenal gland.

PMID- 12213883
TI  - Aberrant apoptosis in thyroid epithelial cells from goiter nodules.
AB  - The specific pathogenesis of nodular goiter and the role of apoptosis in
      goitrogenesis are not known. We sought to examine the regulation of the TNF
      related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL)-induced apoptosis
      pathways in primary thyroid cells from 17 patients with nodular goiter, using 10
      normal thyroids as controls. Both goitrous and normal thyroid cells were
      resistant to recombinant human TRAIL and an agonist anti-Fas antibody under basal
      conditions. However, all normal thyrocytes could be sensitized by TNFalpha/IL
      1beta or interferon gamma/IL-1beta to undergo apoptosis in response to TRAIL or
      FasL, respectively. In contrast, the majority of goiter-derived cells remained
      resistant to TRAIL (12 of 17 samples) or FasL (9 of 17 samples) after cytokine
      pretreatment; 14 of 17 goiter nodules were resistant to at least one death
      ligand. Goiter size was inversely correlated with the sensitivity to TRAIL
      mediated apoptosis. The resistance of goiter cells to TRAIL did not appear to be
      due to transcriptional regulation or cell surface expression of death and decoy
      receptors. However, increased proteasome activity was found in a subset of goiter
      cells resistant to both death ligands, and proteasome inhibitors could sensitize
      these goiter cells to TRAIL-mediated apoptosis. In conclusion, goiter-derived
      thyroid cells are resistant to TRAIL and/or Fas-induced apoptosis in vitro, and
      this may represent a new aspect of aberrant growth regulation in goiter nodules.
      The increased proteasome activity associated with this resistance suggests that
      the proteasome may be an important regulator of apoptosis in nodular goiter.

PMID- 12213884
TI  - IGF-I regulates osteoprotegerin (OPG) and receptor activator of nuclear factor
      kappaB ligand in vitro and OPG in vivo.
AB  - IGF-I, a ubiquitous polypeptide, plays a key role in longitudinal bone growth and
      acquisition. The most predominant effect of skeletal IGF-I is acceleration of the
      differentiation program for osteoblasts. However, in vivo studies using
      recombinant human (rh) IGF-I and/or rhGH have demonstrated stimulation of both
      bone formation and resorption, thereby potentially limiting the usefulness of
      these peptides in the treatment of osteoporosis. In this study, we hypothesized
      that IGF-I modulates bone resorption by regulating expression of osteoprotegerin
      (OPG) and receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL) in
      bone cells. Using Northern analysis in ST2 cells, we found that human IGF-I
      suppressed OPG mRNA in a time- and dose-dependent manner: 100 micro g/LIGF-I (13
      nM) decreased OPG expression by 37.0 +/- 1.8% (P < 0.002). The half maximal
      inhibitory dose of IGF-I was reached at 50 micro g/liter ( approximately 6.5 nM)
      with no effect of IGF-I on OPG message stability. Conditioned media from ST2
      cells confirmed that IGF-I decreased secreted OPG, reducing levels by 42%, from
      12.1-7 ng/ml at 48 h (P < 0.05). Similarly, IGF-I at 100 micro g/liter (13 nM)
      increased RANKL mRNA expression to 353 +/- 74% above untreated cells as assessed
      by real-time PCR. In vivo, low doses of rhGH when administered to elderly
      postmenopausal women only modestly raised serum IGF-I (to concentrations of 18-26
      nM) and did not affect circulating OPG concentrations; however, administration of
      rhIGF-I (30 micro g/kg.d) for 1 yr to older women resulted in a significant
      increase in serum IGF-I (to concentrations of 39-45 nM) and a 20% reduction in
      serum OPG (P < 0.05). In summary, we conclude that IGF-I in a dose- and time
      dependent manner regulates OPG and RANKL in vitro and in vivo. These data suggest
      IGF-I may act as a coupling factor in bone remodeling by activating both bone
      formation and bone resorption; the latter effect appears to be mediated through
      the OPG/RANKL system in bone.

PMID- 12213886
TI  - Involvement of dipeptidyl peptidase IV in extravillous trophoblast invasion and
      differentiation.
AB  - Previously, we reported that dipeptidyl peptidase IV (DPPIV), a membrane-bound
      peptidase, was expressed on human placental cytotrophoblasts. In the present
      study, we focused on DPPIV expression on extravillous trophoblasts (EVTs). In the
      first trimester, DPPIV was expressed in the proximal part of the cell column and
      some EVTs located in the deep portion of the decidua and myometrium. EVTs
      migrating in the decidua from the cell column were negative for DPPIV. In the
      second and third trimesters, almost all EVTs were positive for DPPIV. Because
      negative DPPIV expression was associated with migration or the invasive phenotype
      of EVTs, using JEG-3 cells (choriocarcinoma cell line) that endogenously produce
      DPPIV, the influence of DPPIV on the invasive activity was examined. When a
      competitive inhibitor of DPPIV, diprotin A, was added in Matrigel invasion assay
      system, JEG-3 cells exhibited a significant enhancement of invasion. Because
      hypoxia is reported to reduce trophoblastic invasion, the effect of hypoxia was
      examined on JEG-3 cells. JEG-3 cells became less invasive with increased
      expression of DPPIV when cultured under hypoxic conditions (1% O(2)). These
      results suggest that DPPIV is important for the noninvasive EVT phenotype and the
      down-regulation of this enzyme was strongly associated with migration or invasive
      EVT phenotype.

PMID- 12213885
TI  - Differential effects of thrombin and hypoxia on endometrial stromal and glandular
      epithelial cell vascular endothelial growth factor expression.
AB  - Ovarian steroids and/or premenstrual endometrial hypoxia are thought to restore
      the endometrial vasculature shed during menstruation by elevating endometrial
      vascular endothelial growth factor (VEGF) levels. During the luteal phase, VEGF
      levels peak, progesterone induces estradiol (E(2))-primed human endometrial
      stromal cells (HESCs) to decidualize and express tissue factor (TF), and
      endometrial vascular permeability is enhanced. The latter would present
      circulating clotting factors to decidual cell-expressed TF to form local
      thrombin. HESCs were incubated in serum-supplemented medium containing vehicle
      (control) or 10(-8) M E(2) or 10(-7) M medroxyprogesterone acetate (MPA) or E(2)
      + MPA for 7 d to induce decidualization, while monolayers of human endometrial
      glandular epithelial cells (HEGECs) formed during 4-d incubation of glands. The
      medium was exchanged for a defined medium containing corresponding vehicle or
      steroids +/- thrombin under normoxia or hypoxia (0-1% O(2)). Hypoxia enhanced
      secreted immunoreactive VEGF levels by severalfold in HESCs and HEGECs, but the
      steroids did not affect VEGF output in either cell type under normoxia or
      hypoxia. In E(2) + MPA-decidualized HESCs, VEGF levels were elevated by 0.1 U/ml
      of thrombin, and 0.5-2.5 U/ml of thrombin elicited maximum effects. The addition
      of 0.5 U/ml of thrombin evoked a time-dependent enhancement of VEGF levels and
      about an 8-fold increase at 48 h (P < 0.02; n = 6). Northern blotting indicated
      that E(2) + MPA-decidualized HESCs expressed VEGF(121), VEGF(165), and VEGF(189)
      mRNA, which were enhanced severalfold during 5- to 20-h incubation with thrombin.
      Moreover, TRAP, a synthetic peptide activator of the constitutively expressed
      protease activated receptor-1 thrombin receptor in decidualized HESCs, also
      elevated secreted VEGF levels. By contrast, HEGECs were unresponsive to thrombin
      added alone or with ovarian steroids. These results suggest that thrombin formed
      by progestin-augmented TF levels acts as an autocrine enhancer of VEGF expression
      in decidualized HESCs. Because angiogenesis occurs in a matrix of decidualized
      HESCs, these in vitro results provide a novel mechanism to account for both the
      peak in VEGF and angiogenesis in luteal phase human endometrium.

PMID- 12213887
TI  - Relationship of insulin receptor substrate-1 and -2 genotypes to phenotypic
      features of polycystic ovary syndrome.
AB  - Insulin resistance is a key component in the pathogenesis of polycystic ovary
      syndrome (PCOS) and type 2 diabetes. Polymorphisms in the genes encoding the
      insulin receptor substrate (IRS) proteins, IRS-1 (Gly(972)Arg) and IRS-2
      (Gly(1057)Asp), influence susceptibility to type 2 diabetes. This study was
      undertaken to assess the influence of these polymorphisms on insulin resistance,
      glucose tolerance, and androgen levels in nondiabetic PCOS women. We studied 227
      PCOS subjects including 126 and 48 nondiabetic white and African-American
      subjects, respectively. The IRS-1 Gly(972)Arg allele frequencies were identical
      in whites and African-Americans [0.95 (Gly) and 0.05 (Arg)]. The IRS-2
      Gly(1057)Asp allele frequencies were 0.85 (Gly) and 0.15 (Asp) in African
      Americans and 0.59 (Gly) and 0.41 (Asp) in whites. There was no association of
      IRS-1 genotype with any clinical or hormonal measure in nondiabetic white or
      African-American PCOS subjects. However, nondiabetic subjects with the IRS-2
      Gly/Gly genotype had significantly higher 2-h oral glucose tolerance test glucose
      levels compared with those with Gly/Asp and Asp/Asp genotypes in whites or
      Gly/Asp genotype in African-Americans (there were no Asp/Asp subjects in our
      modest size African-American sample). These results suggest that the IRS-2
      Gly(1057)Asp polymorphism influences blood glucose levels in nondiabetic white
      and African-American women with PCOS. Thus, individuals with the common IRS-2
      Gly/Gly genotype may be at increased risk of developing type 2 diabetes.

PMID- 12213889
TI  - Longitudinal study of plasma pregnenolone and 17-hydroxypregnenolone in full-term
      and preterm neonates at birth and during the early neonatal period.
AB  - Pregnenolone (Preg) and 17-hydroxypregnenolone (17OH-Preg) are marker steroids
      that are elevated in the 3beta-hydroxysteroid-dehydrogenase-II deficiency form of
      congenital adrenal hyperplasia. The aim of this study was to establish normative
      data for both steroids in healthy preterm (28-33 and 34-37 wk gestation) and full
      term infants, because reference values for the early neonatal period do not
      exist. At delivery, the main source of Preg is the placenta, because the highest
      levels were found in the retroplacental space (median, 141.31 nmol/liter), with
      no significant difference between preterm and full-term pregnancies. The fetal
      adrenals provide most of the circulating 17OH-Preg in full-term neonates, as
      demonstrated by a marked arteriovenous gradient in cord blood (40.96 nmol/liter
      vs. 10.77 nmol/liter). 17OH-Preg levels in the umbilical arteries were
      significantly lower in premature infants than in full-term infants (8.06
      nmol/liter vs. 40.96 nmol/liter). During the first 2 postnatal weeks, Preg
      concentrations showed a rapid and significant fall in early preterm infants
      [95.78 nmol/liter (0 h) to 36.69 nmol/liter (d 14)] as well as in full-term
      infants [66.62 nmol/liter (0 h) to 14.81 nmol/liter (d 6)]. In addition, a
      significant fall in 17OH-Preg levels was found in full-term neonates [40.96
      nmol/liter (0 h) to 11.32 nmol/liter (d 6)]. After 12 h, significantly higher
      levels for Preg and 17OH-Preg were found in early preterm infants (98.01
      nmol/liter and 69.13 nmol/liter), compared with full-term neonates (36.29
      nmol/liter and 28.55 nmol/liter, P < 0.05), reflecting the increased fetocortical
      activity as a response to the stress of delivery in the prematures. With these
      longitudinal data, it is now possible to confirm or exclude the diagnosis of
      3beta-hydroxysteroid-dehydrogenase-II deficiency within the first postnatal week.

PMID- 12213891
TI  - Three novel mutations in CYP21 gene in Brazilian patients with the classical form
      of 21-hydroxylase deficiency due to a founder effect.
AB  - Three different new mutations were found after CYP21 gene sequencing in three
      unrelated patients with the classical form of the 21-hydroxylase deficiency.
      These mutations were also screened in their affected relatives. In one patient
      and her brother, both affected with the simple virilizing form and in their aunt,
      with the nonclassical form, an AG>GG transition was found in the acceptor site of
      intron 2. In another patient with the salt wasting form, we found a 1003 1004
      insA, in exon 4, that altered the reading frame and created a stop codon in codon
      297. In the third patient and his sister, we found a C>T transition in codon 408.
      This transition led to the substitution of arginine by cysteine (R408C) in a
      conserved region where arginine is conserved in at least four different species.
      These siblings with the R408C mutation, both affected with the salt wasting form,
      have the IVS2-13A/C>G mutation in the other allele, suggesting that the R408C
      should lead to complete impairment of enzymatic activity. To rule out the
      possibility of polymorphism, R408C was screened through allele specific PCR, and
      it was not found in 100 normal alleles. The screening of these three new
      mutations by allele-specific PCR or enzymatic restriction in 212 CAH patients
      disclosed their presence in 2.3% (9/387) of the alleles. All three new mutations
      were found in compound heterozygous state with previously known mutations.
      Microsatellite studies, using markers flanking CYP21 gene, revealed that each new
      mutation presents the same haplotype, suggesting a gene founder effect, similar
      to what was previously observed with the G424S mutation also described in our
      population. Although microconversion events are the main cause of mutations in
      the CYP21 gene, random mutations with a common origin can also be the cause of 21
      hydroxylase deficiency.

PMID- 12213890
TI  - Regulation of hepatic low-density lipoprotein receptor, 3-hydroxy-3
      methylglutaryl coenzyme A reductase, and cholesterol 7alpha-hydroxylase mRNAs in
      human liver.
AB  - To characterize the coordinate regulation of cholesterol metabolism in human
      liver, we simultaneously quantified mRNA levels of cholesterol 7alpha-hydroxylase
      (CYP7A1), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), and low-
      density lipoprotein receptors (LDLRs) in liver biopsies from 76 patients
      undergoing cholecystectomy. The three transcript levels were not different
      between untreated gallstone and gallstone-free patients and not significantly
      altered by 10-d exclusion of dietary cholesterol. Treatment with chenodeoxycholic
      acid suppressed CYP7A1 and to a lesser extent HMGR mRNA levels. Cholestyramine
      treatment increased CYP7A1, but also HMGR and LDLR mRNA, and statins only
      increased HMGR mRNA. Resin + statin treatment increased all mRNA species. In
      untreated patients, the mRNA levels of HMGR and LDLR were more strongly
      correlated (r = +0.60) than those of CYP7A1 and HMGR (r = +0.49) or CYP7A1 and
      LDLR (r = +0.21). In the treated patients, in whom bile acid synthesis was
      suppressed or stimulated, mRNA levels of CYP7A1 and HMGR (r = +0.84) as well as
      CYP7A1 and LDLR (r = +0.62) were more strongly correlated than those of HMGR and
      LDLR (r = +0.59). The coordinate control of HMGR and LDLR mRNA levels reflects
      their common regulation by shared transcriptional activation. In contrast,
      following changes in bile acid flux through the liver, CYP7A1 gene expression
      becomes a strong modulator of hepatic cholesterol metabolism.

PMID- 12213892
TI  - Clinical, genetic, and functional characterization of adrenocorticotropin
      receptor mutations using a novel receptor assay.
AB  - The ACTH receptor (MC2R) is expressed predominantly in the adrenal cortex, but is
      one of five G protein-coupled, seven-transmembrane melanocortin receptors (MCRs),
      all of which bind ACTH to some degree. Testing of MC2R activity is difficult
      because most cells express endogenous MCRs; hence, ACTH will elicit background
      activation of assayable reporter systems. Inactivating mutations of MC2R lead to
      hereditary unresponsiveness to ACTH, also known as familial glucocorticoid
      deficiency (FGD). These patients are usually seen in early childhood with very
      low cortisol concentrations, normal mineralocorticoids, hyperpigmentation, and
      increased bodily growth. Several MC2R mutations have been reported in FGD, but
      assays of the activities of these mutants are cumbersome. We saw two patients
      with typical clinical findings of FGD. Genetic analysis showed that patient 1 was
      homozygous for the mutation R137W, and patient 2 was a compound heterozygote for
      S74I and Y254C. We tested the activity of these mutations in OS-3 cells, which
      are unresponsive to ACTH but have intact downstream cAMP signal transduction. OS
      3 cells transfected with a cAMP-responsive luciferase reporter plasmid (pCREluc)
      were unresponsive to ACTH, but cotransfection with a vector expressing human MC2R
      increased luciferase activity more than 40-fold. Addition of ACTH to cells
      cotransfected with the pCREluc reporter and wild-type MC2R activated luciferase
      expression with a 50% effective concentration of 5.5 x 10(-9) M ACTH, which is
      similar to previously reported values. By contrast, the MC2R mutant R137W had low
      activity, and the S74I or Y254C mutants elicited no measurable response. This
      assay provides excellent sensitivity in an easily assayed transient transfection
      system, providing a more rapid and efficient measurement of ACTH receptor
      activity.

PMID- 12213893
TI  - Mutations of the PRKAR1A gene in Cushing's syndrome due to sporadic primary
      pigmented nodular adrenocortical disease.
AB  - Primary pigmented nodular adrenocortical disease (PPNAD) is a cause of ACTH
      independent Cushing's syndrome. This condition can be difficult to diagnose
      because hypercortisolism may be periodic and adrenal imaging may not demonstrate
      an adrenal tumor. PPNAD can be part of the Carney complex (CNC), an autosomal
      dominant multiple neoplasia syndrome. Germline mutations of the regulatory
      subunit R1A of PKA (PRKAR1A) have been observed in about 45% of CNC kindreds. To
      improve our understanding of sporadic PPNAD and develop a potential diagnostic
      tool, we investigated the genetics of patients with sporadic and isolated PPNAD.
      Patients undergoing surgery for bilateral ACTH-independent Cushing's syndrome in
      whom pathological examination revealed PPNAD were subjected to endocrinological
      investigations and a systematic search for other manifestations of CNC. The
      PRKAR1A gene was sequenced using DNA from frozen adrenal tissues and leukocytes
      from three patients with sporadic isolated PPNAD and using leukocyte DNA from two
      additional patients. Different inactivating germline mutations of the PRKAR1A
      gene were found in the five patients. For three cases, study of the parents' DNA
      demonstrated a de novo mutation. One patient presented with an unusual 2.5-cm
      macronodule of the right adrenal mimicking an adrenal adenoma. A somatic 16-bp
      deletion of PRKAR1A gene was also found in this macronodule. Inactivating
      germline mutations of PRKAR1A are frequent in sporadic and isolated cases of
      PPNAD. The wild-type allele can be inactivated by somatic mutations, consistent
      with the hypothesis of the gene being a tumor suppressor gene. Thus, genetic
      analysis can be of help to the clinician in the diagnosis of this difficult form
      of adrenal Cushing's syndrome.

PMID- 12213894
TI  - A minimal mathematical model of calcium homeostasis.
AB  - A mathematical model of calcium homeostasis is presented in which the controlling
      factors are the plasma concentrations of calcium, PTH, and calcitriol, and the
      effector organs are the parathyroids, bone, kidney, and intestine. Other factors
      can be added as the need arises. The model is aimed at simulating what happens in
      a single individual, but its parameters and variables were adjusted to the
      corresponding published average values. Simulations of published observations in
      humans undergoing the infusion of calcium or its chelators are presented. With a
      single exception, these simulations provided a good fit to the data. The response
      of the system to extrinsic perturbations was characterized by simulating chronic
      infusions of calcium, PTH, and calcitriol. Finally, the steady state response to
      perturbations in some of its parameters (the secretory mass of the parathyroids
      and the affinity and/or sensitivity of the calcium, PTH, and calcitriol
      receptors) and to renal failure were also investigated in an attempt to analyze
      the pathogenesis of clinical hypo- or hypercalcemias. In its present form the
      model cannot be used to base clinical decisions in individual cases. However, it
      requires modest computational resources, and clinicians with a modest
      mathematical background can manipulate it. It is a useful tool for the analysis
      of general mechanisms of the diseases of calcium metabolism and for the design of
      clinical experiments aimed at characterizing these diseases. The model can also
      be the core of future autoadaptive extensions to be used in individual patients.

PMID- 12213896
TI  - 17Beta-estradiol up-regulates vascular endothelial growth factor receptor-2
      expression in human myometrial microvascular endothelial cells: role of estrogen
      receptor-alpha and -beta.
AB  - Estrogen has a cardiovascular protective role in women due in part to its effect
      on the vasculature. The roles of the two estrogen receptors (ERs), ERalpha and
      ERbeta, in the vascular actions of estrogen are unclear, as are effects of
      estrogen on microvascular endothelial cells (MEC) derived from sex steroid
      responsive tissues. The present study demonstrates that 17beta-estradiol, but not
      progesterone, increases vascular endothelial growth factor (VEGF) receptor
      (VEGFR) expression on human myometrial MEC measured using biotin-recombinant
      human (rh) VEGF(165) and flow cytometry. This response occurred in a time- and
      dose-dependent manner, with significantly increased rhVEGF(165) binding at 3 h
      and maximal responses between 0.1 and 10 nmol/liter 17beta-estradiol, which was
      blocked by the antiestrogen ICI 182,780. Approximately 60% of samples
      demonstrated this response to 17beta-estradiol. All samples of myometrial MEC
      expressed both ERbeta mRNA and protein demonstrated by semiquantitative RT-PCR
      and Western blotting. However, ERalpha mRNA and protein were expressed in only 13
      of 21 MEC samples. There was a significant association between ERalpha expression
      in myometrial MEC and their ability to respond to 17beta-estradiol by increasing
      rhVEGF(165) binding. 17beta-estradiol increased VEGFR-2 expression in ERalpha
      expressing MEC isolates, which also demonstrated increased rhVEGF(165) binding,
      but failed to have these effects on ERalpha negative samples. Similarly, 17beta
      estradiol augmented VEGF-induced MEC proliferation in ERalpha-expressing MEC
      samples, which was blocked by ICI 182,780. These observations suggest that 17beta
      estradiol increases VEGFR-2 expression on human myometrial MEC promoting
      endothelial cell proliferation, an effect that varies between subjects and
      appears to be mediated primarily by ERalpha.

PMID- 12213897
TI  - Left ventricular myocardial impairment in subclinical hypothyroidism assessed by
      a new ultrasound tool: pulsed tissue Doppler.
AB  - Pulsed tissue Doppler (TD) is a new ultrasound tool that allows quantification of
      myocardial regional wall motion. To investigate the cardiac effects of
      subclinical hypothyroidism (SH), the present study assessed left ventricular (LV)
      myocardial regional function in SH by pulsed TD. Twenty women with SH and 20
      healthy women underwent standard Doppler echocardiograms and pulsed TD, placing a
      sample volume at the level of posterior septum and LV mitral annulus. Myocardial
      systolic and diastolic velocities and time intervals were determined for both
      levels. Doppler-echocardiographic and TD measurements were adjusted for body
      surface area and heart rate. Standard Doppler showed an increases in LV
      preejection period, preejection period/LV ejection time ratio, and isovolumic
      relaxation time (IVRT) in SH. By TD analysis, myocardial precontraction time
      (PCT(m)), PCT(m)/myocardial contraction time ratio, and myocardial relaxation
      time (RT(m)) were prolonged at the level of both posterior septum and mitral
      annulus in SH. In the whole population, IVRT, PCT(m), and RT(m) were negatively
      related to FT(4), whereas IVRT, PCT(m)/myocardial contraction time ratio, and
      RT(m) were positively correlated to TSH. In conclusion, this study underscores
      the usefulness of TD to detect cardiac functional abnormalities due to stable SH,
      mainly by changes in myocardial time intervals in several LV segments.

PMID- 12213898
TI  - IGF-I/IGF-binding protein-3 combination improves insulin resistance by GH
      dependent and independent mechanisms.
AB  - IGF-I has been shown to enhance insulin sensitivity in patients with type I and
      type II diabetes. IGF-I suppresses GH, and this raises the question of whether
      its ability to enhance insulin sensitivity is mediated solely through a reduction
      in GH's antiinsulin actions. This study was conducted to determine whether
      administration of a GH receptor antagonist to patients with acromegaly and
      insulin resistance would result in improvement in insulin sensitivity and whether
      IGF-I had any additional insulin-sensitizing effects over and above those induced
      by its ability to suppress GH secretion. Five patients with active acromegaly
      were treated for 2 wk with a GH receptor antagonist. The GH receptor antagonist
      was effective, as IGF-I fell 65%, and mean GH values rose 42%. Mean fasting
      insulin fell from 39 +/- 6 to 30 +/- 7 micro U/ml, and this was accompanied by a
      9% decrease in fasting glucose. After treatment the insulin sensitivity index was
      2.7 +/- 1.0 x 10(-4)/min. micro U/ml compared with a baseline value of 1.65 +/-
      0.8 x 10(-4)/min. micro U/ml (P < 0.015). Subsequently, the subjects were treated
      with the receptor antagonist plus IGF-I/IGF-binding protein-3 given by sc
      injection (1 mg/kg daily). After 2 wk of the combined treatment, fasting insulin
      fell from 49 +/- 9 to 29 +/- 7 micro U/ml, and fasting glucose fell by 14%. The
      insulin sensitivity index improved to 4.34 +/- 1.3 x 10(-4)/min. micro U/ml,
      which was significantly greater than the value obtained after treatment with the
      GH antagonist alone. Although only a limited number of subjects were studied, the
      results strongly suggest that IGF-I has insulin-sensitizing actions that are
      independent of its ability to suppress GH secretion. These findings necessitate
      further studies into the non-GH-related mechanism by which IGF-I enhances insulin
      sensitivity.

PMID- 12213900
TI  - Human fallopian tubes express prostacyclin (PGI) synthase and cyclooxygenases and
      synthesize abundant PGI.
AB  - Animal studies unequivocally support the indispensable role of prostaglandin (PG)
      and cyclooxygenase (COX) in ovulation and implantation. Available data also
      suggest that PG and COX may be important in the transport of embryos. The effects
      of PGE(2) and PGF(2alpha) on the contractility of human tubal muscle have been
      studied extensively; the expression of COX in human fallopian tubes was also
      reported. Despite all these, two fundamentally important questions remained to be
      answered: 1) which PGs are produced by human fallopian tubes; and 2) which COX
      isoform(s) is expressed by the fallopian tubes. We used reverse-phase HPLC to
      study the metabolism of [1-(14)C] arachidonic acid by the fallopian tubes. We
      found that 6 keto-PGF(1alpha), a stable metabolite of prostacyclin (PGI), and
      PGE(2) constituted 56% +/- 10% and 35% +/- 10% (mean +/- SEM, four samples),
      respectively, of total eicosanoids synthesized. Western blot analysis revealed
      the expression of both COX isoforms. Immunohistochemistry study showed that both
      COX-1 and -2 were localized to nonciliated epithelia and tubal smooth muscle. In
      addition, COX-2 was also expressed in ciliated epithelial cells. Western blot
      analysis revealed the expression of PGI synthase (PGIS) and PGI receptor by
      fallopian tubes. Immunohistochemistry confirmed the expression of PGIS by luminal
      epithelia, tubal smooth muscle, vascular endothelial cells, and vascular smooth
      muscle cells. Iloprost, a PGI analog, inhibited the activities of circular and
      longitudinal muscles of the fallopian tube. Thus, the fallopian tube expresses
      both COX isoforms and PGIS. Furthermore, it is a source and a target of PGI. PGI
      and COX may be important to gamete function, embryo transport, and embryo
      development.

PMID- 12213901
TI  - WT1 and DAX-1 inhibit aromatase P450 expression in human endometrial and
      endometriotic stromal cells.
AB  - The orphan nuclear receptor steroidogenic factor-1 (SF-1) induces the expression
      of Mullerian inhibiting substance (MIS) and many steroidogenic genes, including
      aromatase P450 (P450arom). Dosage-sensitive sex reversal adrenal hypoplasia
      congenita critical region on the X chromosome gene 1 (DAX-1) inhibits SF-1
      mediated induction of MIS and other steroidogenic genes, whereas Wilms' tumor
      suppressor gene (WT1) augments SF-1-mediated MIS expression. The effects of WT1
      on steroidogenesis or P450arom expression have not been explored to date. In
      human endometriotic stromal cells, extremely high levels of P450arom mRNA and
      enzyme activity are present. Prostaglandin E(2) stimulates cAMP formation, SF-1
      binding activity, P450arom mRNA levels, and estrogen synthesis in endometriotic
      stromal cells. Stromal cells of eutopic endometrium from disease-free women, on
      other hand, do not contain readily detectable levels of P450arom mRNA. Thus, we
      evaluated herein the possible roles of WT1 and DAX-1 in cAMP/SF-1-mediated
      regulation of P450arom expression in endometriotic and endometrial stromal cells.
      We also determined the cellular distribution and levels of these transcription
      factors in pathological endometriotic vs. normal eutopic endometrial tissues by
      immunohistochemistry to understand their in vivo roles. In vitro transcriptional
      regulation studies showed that both WT1 and DAX-1 inhibited cAMP and/or SF-1
      induced P450arom promoter activity in a dose-dependent fashion in cultured human
      endometriotic and endometrial stromal cells. Site-directed disruption of the SF-1
      binding site (-136/-124 bp) in the P450arom promoter abolished basal or cAMP/SF-1
      induced promoter activity in the presence or absence of WT1 or DAX-1.
      Immunohistochemistry and H-scoring showed that DAX-1 was ubiquitously present in
      epithelial and stromal cells of both tissues. WT1, on the other hand, was
      preferentially expressed in stromal (vs. epithelial) cells. Moreover, WT1 levels
      in endometriotic stromal cells are significantly down-regulated compared with
      normal endometrial stromal cells. In summary, WT1 or DAX-1 inhibits cAMP-SF-1
      pathway-dependent P450arom expression in cultured human endometriotic and
      endometrial stromal cells. In vivo down-regulation of WT1 in endometriotic
      stromal cells (vs. normal endometrial stromal cells) may in part be responsible
      for aberrantly increased P450arom expression and estrogen formation in this
      pathological tissue.

PMID- 12213902
TI  - Complete androgen insensitivity syndrome caused by a novel mutation in the ligand
      binding domain of the androgen receptor: functional characterization.
AB  - Mutations in the X-linked androgen receptor (AR) gene cause the androgen
      insensitivity syndrome by impairing androgen-dependent male sexual
      differentiation to varying degrees. Complete androgen insensitivity (CAIS) yields
      an external female phenotype, whereas affected cases of partial androgen
      insensitivity have various ambiguities of the genitalia. Here we describe a 46,XY
      phenotypically female patient with all of the characteristics of CAIS, i.e.
      primary amenorrhea, no axillary or pubic hair, female external genitalia, no
      uterus, and undescended testes. Defects in testosterone and dihydrotestosterone
      synthesis were excluded. The molecular basis of the disease was clarified by
      means of direct sequencing of PCR-amplified exonic fragments of the AR gene. An A
      to C transition in exon 4 of the AR gene led to a novel missense His(689)Pro
      mutation in the ligand-binding domain of the AR protein. Functional studies
      demonstrated that the mutated AR is unable to efficiently bind its natural ligand
      dihydrotestosterone and to trans-activate known androgen response elements.
      Analysis of the structural consequences of the His(689)Pro substitution suggests
      that this mutation is likely to perturb the conformation of the second helix of
      the AR ligand-binding domain, which contains residues critical for androgen
      binding.

PMID- 12213903
TI  - Calcitonin gene-related peptide (CGRP) and CGRP receptor expression at the human
      implantation site.
AB  - Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide produced
      by tissue-specific alternative splicing of the primary transcript of the
      calcitonin gene. The objectives of this study were: 1) to determine the
      expression of CGRP and its receptor at the human implantation site, and 2) to
      examine the possible in vitro effect of this neuropeptide on two major partners
      of implantation, decidual cells and extravillous cytotrophoblasts.
      Immunohistological analysis of first-trimester placental chorionic villi showed
      CGRP in decidual cells and glandular cells, but not in extravillous trophoblast
      cells. CGRP expression was confirmed in cultured decidual cells by Southern blot
      analysis and immunocytochemistry and by RIA in culture medium. Transcripts of
      calcitonin receptor-like receptor were detected by Southern blot analysis of RT
      PCR amplicons from both decidual and extravillous trophoblast cells, whereas
      transcripts for the receptor activity-modifying protein 1 were detected in
      decidual cells only. In vitro, CGRP stimulated cAMP production but not nitric
      oxide (NO) release by cultured decidual cells; in contrast CGRP increased NO
      release but not cAMP production in cultured extravillous trophoblasts. The
      presence of NO synthase (endothelial and inducible) was confirmed by
      immunodetection in extravillous trophoblasts, both in situ and in vitro. This
      study points to a paracrine and autocrine effect of CGRP on decidual and
      extravillous trophoblast cells, two major actors in implantation.

PMID- 12213904
TI  - Intense expression of the b7-2 antigen presentation coactivator is an unfavorable
      prognostic indicator for differentiated thyroid carcinoma of children and
      adolescents.
AB  - Previous observations suggest that an immune response against thyroid carcinoma
      could be important for long-term survival. We recently found that infiltration of
      thyroid carcinoma by proliferating lymphocytes is associated with improved
      disease-free survival, but the factors that control lymphocytic infiltration and
      proliferation are largely unknown. We hypothesized that the antigen presentation
      coactivators (B7-1 and B7-2), which are important in other immune-mediated
      thyroid diseases, might be important in lymphocytic infiltration of thyroid
      carcinoma. To test this, we determined B7-1 and B7-2 expression by
      immunohistochemistry [absent (grade 0) to intense (grade 3)] in 27 papillary
      (PTC) and 8 follicular (FTC) thyroid carcinomas and 9 benign thyroid lesions. B7
      1 and B7-2 were expressed by the majority of PTC and FTC (78% of PTC and 100% of
      FTC expressed B7-1; 88% of PTC and 88% of FTC expressed B7-2). B7-1 expression
      was more intense in PTC (1.4 +/- 0.2; P = 0.01) and FTC (2.6 +/- 0.2; P < 0.001)
      than in benign tumors (0.57 +/- 0.30) or presumably normal adjacent thyroid (0.07
      +/- 0.07) and was more intense in carcinoma that contained lymphocytes (1.95 +/-
      0.21) than in carcinoma that did not (1.08 +/- 0.26; P = 0.016). B7-2 expression
      was of similar intensity in benign and malignant tumors (PTC, 1.6 +/- 0.2; FTC,
      2.1 +/- 0.4; benign, 1.86 +/- 0.4), but was more intense than in presumably
      normal adjacent thyroid (0.64 +/- 0.25; P </= 0.013). B7-2 expression also
      correlated with the number of tumor-associated lymphocytes per high power field
      (r = 0.38; P = 0.02). Recurrence developed exclusively from tumors that expressed
      B7-2, and intense B7-2 expression was associated with a reduced probability of
      remission (P = 0.04). In conclusion, these data support the hypothesis that the
      antigen presentation coactivators B7-1 and B7-2 may be important for lymphocytic
      infiltration and the immune response against thyroid carcinoma.

PMID- 12213905
TI  - Variation at the aldosterone synthase (CYP11B2) locus contributes to hypertension
      in subjects with a raised aldosterone-to-renin ratio.
AB  - The aldosterone-to-renin ratio (ARR) is a marker of aldosterone activity in
      hypertension. We examined the relationship of the ARR to the distribution of two
      biallelic polymorphisms at the CYP11B2 gene locus. One polymorphism affects a
      putative steroidogenic factor-1 binding site (-344 T/C) in the 5'-regulatory
      region, whereas the other marker reflects replacement of the intron-2 from
      CYP11B2 with that from the neighboring gene encoding 11beta-hydroxylase (CYP11B1;
      wild-type/conversion). We studied consecutive referrals to the Tayside
      hypertension clinic in 1998. Because the specificity of ARR (pmol/liter/ng/ml/h)
      for hyperaldosteronism increases with its threshold, ARRs of at least 750 and
      1000 were used. A total of 375 patients were assessed; 86.9% had complete data.
      There were significant excesses of steroidogenic factor-1 (T) (ARR >/= 750, 0.62
      vs. 0.51, P = 0.014; ARR >/= 1000, 0.63 vs. 0.51, P = 0.039) and intron-2
      (conversion) (ARR >/= 750, 0.49 vs. 0.41, P = 0.205; ARR >/= 1000, 0.54 vs. 0.41,
      P = 0.029) alleles in patients with a raised ARR. The odds ratio for a raised ARR
      was 2.27 [95% confidence interval, 1.01, 5.09; P < 0.05] comparing patients with
      a homozygous haplotype for these alleles with those without any such alleles, and
      this risk increased with age. This study supports the notion that there is a
      genetic component that regulates aldosterone production and that
      hyperaldosteronism might develop over time in susceptible individuals.

PMID- 12213907
TI  - An ATG repeat in the 3'-untranslated region of the human resistin gene is
      associated with a decreased risk of insulin resistance.
AB  - Resistin is overexpressed in human adipose tissue of obese individuals and is
      likely to modulate insulin sensitivity. Resistin is, therefore, a candidate gene
      for insulin resistance. We searched for polymorphisms in the resistin gene by
      single strand conformation polymorphism and direct sequencing. An ATG triplet
      repeat in the 3'-untranslated region was identified and considered for
      association with insulin resistance. Three alleles were identified (allele 1: 8
      repeats, allele frequency, 0.3%; allele 2: 7 repeats; allele frequency, 94.5%;
      allele 3: 6 repeats; allele frequency, 5.2%). Two hundred and three unrelated
      white Caucasian nondiabetic subjects from Sicily and 456 from the Gargano area
      (center east coast of Italy) were analyzed. Among Sicilians, subjects carrying
      allele 3 had a lower fasting insulin and insulin resistance index (homeostasis
      model assessment of insulin resistance; P < 0.001 for both) and glucose (P =
      0.025) and insulin (P = 0.002) levels during the oral glucose tolerance test. In
      subjects from Gargano, those carrying allele 3 had lower fasting plasma glucose
      levels and serum triglycerides (P = 0.01 for both). When the 2 populations were
      analyzed together, subjects carrying allele 3 had lower fasting insulin levels (P
      < 0.005), homeostasis model assessment of insulin resistance (P < 0.005), and
      serum triglycerides (P = 0.01). In conclusion, our data suggest that subjects
      carrying allele 3 of the resistin gene are characterized by relatively high
      insulin sensitivity.

PMID- 12213909
TI  - Galectin-3 is not an universal marker of malignancy in thyroid nodular disease in
      children and adolescents.
AB  - Current methods of research into thyroid nodular disease (TND) based on the
      polymerase chain reaction (PCR) and reverse-transcription (RT) permit the
      detection of some markers, even in poorly cellular biological material. The
      findings from fine-needle aspiration biopsy (FNAB), the most commonly used
      procedure in TND, do not always correlate with the postoperative
      histopathological diagnosis, sometimes giving a false negative result. The aim of
      this present study was to improve the classical cytological evaluation of the
      material obtained with ultrasound-guided biopsy with a RT-PCR based technique in
      order to detect carcinoma even in a minimally invasive form. Aspirate from the 30
      patients included in the study was smeared for conventional cytology (H+E and MGG
      staining) and the leftover material in the needle was frozen for subsequent PCR
      analysis. Fine-needle aspiration specimens were evaluated for the presence of
      galectin-3 (GAL-3), the most promising molecular marker of malignancy. As a
      positive control for cells of follicular origin, thyroglobulin (Tg) gene
      expression was performed. RT-PCR was performed on extracted RNA and with specific
      primers for the screened genes, based on a one-step reaction with a Biometra PCR
      machine. Tg expression was observed in 23 aspirates, among which 10 were positive
      for the expression of GAL-3 [3 cases of PTC, 1 an oxyphilic variant of FTC, 1 an
      oxyphilic variant of follicular adenoma (FA), 1 a foetal variant of FA, 2 of
      Hashimoto thyroiditis (HT) and 2 of HT with coexisting FA]. Our results are the
      first evidence that GAL-3 expression, previously documented in thyroid carcinoma
      of follicular origin, is also present in Hashimoto thyroiditis. This study
      reveals some limitations in nodule or multiple nodules of benign character. If
      the diagnosis of HT is excluded, then the usefulness of the method in the
      diagnosis of malignancy may still be very high.

PMID- 12213908
TI  - Genetic variants at the resistin locus and risk of type 2 diabetes in Caucasians.
AB  - Resistin is a newly identified hormone secreted by adipocytes that inhibits
      insulin action on peripheral tissues. The aim of our study was to investigate
      whether genetic variability at this locus is associated with the risk of type 2
      diabetes. By sequencing 32 subjects with type 2 diabetes, we identified 8 single
      nucleotide polymorphisms (SNPs) in the 5'-flanking region and introns of the
      resistin gene. Allele and genotype distributions were determined for all 8 SNPs
      in 312 cases with type 2 diabetes and 303 nondiabetic controls, all of Caucasian
      origin. No significant association with type 2 diabetes was found at any of the
      polymorphic loci. However, an interactive effect of genotype at SNP 6 (IVS2 +
      181G-->A) and obesity was a significant determinant of type 2 diabetes risk in
      this population. The relative risk of diabetes for the A/A genotype was 4.8 (95%
      confidence interval, 1.1-21.0) in individuals above the median for body weight,
      but only 0.7 (95% confidence interval, 0.2-2.1) in those below the median. This
      difference between relative risks was significant (chi(2) = 4.5; P = 0.03). A
      similar, but much weaker, interaction with obesity was observed for SNPs in
      linkage disequilibrium with SNP6. In conclusion, resistin does not appear to be a
      major gene for type 2 diabetes. However, our data suggest a synergistic effect of
      sequence differences at the resistin locus and obesity on risk of type 2
      diabetes. Further studies are needed to confirm this finding in other
      populations.

PMID- 12213912
TI  - Orchestrating the cell cycle in yeast: sequential localization of key mitotic
      regulators at the spindle pole and the bud neck.

PMID- 12213913
TI  - Phenotypic switching and filamentation in Candida glabrata.
AB  - Candida glabrata switches spontaneously, reversibly and at high frequency among
      the following four phenotypes distinguishable by graded colony colouration on
      CuSO(4)-containing agar: white (Wh), light brown (LB), dark brown (DB) and very
      dark brown (vDB). These phenotypes also differ in a graded fashion in the level
      of expression of the metallothionein gene MTII (Wh<LB<DB>vDB), the frequency of
      switching (Wh>LB>DB>vDB) and colouration on phloxine B-containing agar
      (Wh>LB>DB>vDB). Switching among the four graded phenotypes is referred to as 'the
      core switching system'. An additional switch phenotype, 'irregular wrinkle'
      (IWr), has been identified, which exhibits a highly wrinkled colony morphology.
      The characteristics of IWr suggest that switching to and from this phenotype
      represents a second high-frequency switching system. A microscopic analysis
      revealed that during the first 3 days of colony development, cells in the centres
      of Wh, LB, DB and vDB colonies expressed almost exclusively the budding yeast
      phenotype. After 3 days, however, pseudohyphae and cells extending tubes
      accumulated, so that by 7 days the proportions of these two cellular phenotypes
      reached 40-50% and 10-20%, respectively. In contrast, IWr colonies were composed
      almost exclusively of pseudohyphae through the first 6 days of colony
      development. After 6 days, IWr colonies began to accumulate both budding yeast
      cells and tubes. The tubes formed by C. glabrata reached lengths of up to six
      cell diameters, but the tubes did not represent traditional compartmentalized
      hyphae. Tube growth ended when the tube tip expanded to form a bud. Tubes then
      functioned as corridors for daughter nucleus migration to the apical bud, and
      were ultimately left uncompartmentalized and nucleus free. Core switching,
      pseudohypha formation and tube formation occurred in a majority of 62 tested
      clinical isolates, demonstrating that these developmental programmes are general
      characteristics of most strains of C. glabrata.

PMID- 12213914
TI  - Munumbicins, wide-spectrum antibiotics produced by Streptomyces NRRL 30562,
      endophytic on Kennedia nigriscans.
AB  - Munumbicins A, B, C and D are newly described antibiotics with a wide spectrum of
      activity against many human as well as plant pathogenic fungi and bacteria, and a
      Plasmodium sp. These compounds were obtained from Streptomyces NRRL 3052, which
      is endophytic in the medicinal plant snakevine (Kennedia nigriscans), native to
      the Northern Territory of Australia. This endophyte was cultured, the broth was
      extracted with an organic solvent and the contents of the residue were purified
      by bioassay-guided HPLC. The major components were four functionalized peptides
      with masses of 1269.6, 1298.5, 1312.5 and 1326.5 Da. Numerous other related
      compounds possessing bioactivity, with differing masses, were also present in the
      culture broth extract in lower quantities. With few exceptions, the peptide
      portion of each component contained only the common amino acids threonine,
      aspartic acid (or asparagine), glutamic acid (or glutamine), valine and proline,
      in varying ratios. The munumbicins possessed widely differing biological
      activities depending upon the target organism. For instance, munumbicin B had an
      MIC of 2.5 microg x ml(-1) against a methicillin-resistant strain of
      Staphylococcus aureus, whereas munumbicin A was not active against this organism.
      In general, the munumbicins demonstrated activity against Gram-positive bacteria
      such as Bacillus anthracis and multidrug-resistant Mycobacterium tuberculosis.
      However, the most impressive biological activity of any of the munumbicins was
      that of munumbicin D against the malarial parasite Plasmodium falciparum, having
      an IC(50) of 4.5+/-0.07 ng x ml(-1). This report also describes the potential of
      the munumbicins in medicine and agriculture.

PMID- 12213915
TI  - Cloning and expression of the phosphotriesterase gene hocA from Pseudomonas
      monteilii C11.
AB  - The cloning of a gene encoding the novel phosphotriesterase from Pseudomonas
      monteilii C11, which enabled it to use the organophosphate (OP) coroxon as its
      sole phosphorus source, is described. The gene, called hocA (hydrolysis of
      coroxon) consists of 501 bp and encodes a protein of 19 kDa. This protein had no
      sequence similarity to any proteins in the SWISS-PROT/GenBank databases. When a
      spectinomycin-resistance cassette was placed in this gene, phosphotriesterase
      activity was abolished and P. monteilii C11 could no longer grow with coroxon as
      the sole phosphorus source. Overexpression and purification of HocA as a maltose
      binding protein fusion produced a protein having a broad substrate specificity
      across oxon and thion OPs. Michaelis-Menten kinetics were observed with the oxon
      OPs, but not with the thion OPs. End-product inhibition was observed for coroxon
      hydrolytic activity. Increased expression of hocA was observed from an
      integrative hocA-lacZ fusion when cultures were grown in the absence of
      phosphate, suggesting that it might be part of the Pho regulon, but the phosphate
      regulated promoter was not cloned in this study. This is believed to be the first
      study in which a gene required for an organism to grow with OP pesticides as a
      phosphorus source has been isolated.

PMID- 12213916
TI  - Physiological role of the glutathione-dependent formaldehyde dehydrogenase in the
      methylotrophic yeast Candida boidinii.
AB  - The methylotrophic yeast Candida boidinii exhibits formaldehyde dehydrogenase
      activity (FLD, EC 1.2.1.1) during growth on methanol as a sole carbon source. The
      structural gene, FLD1, was cloned from a genomic library of C. boidinii. The 1263
      bp FLD1 gene contained a 123 bp intron and its exon encoded a gene product of 380
      amino acids, whose predicted amino acid sequence showed high similarity to the
      sequences of FLDs from other organisms. The FLD1 gene was disrupted in the C.
      boidinii genome by one-step gene disruption. The fld1Delta strain could not grow
      on methanol as a carbon source under methanol-limited chemostat culture
      conditions, even with low dilution rates (D<0.05 x h(-1)), whereas a strain with
      a disruption in the gene for formate dehydrogenase (FDH; another NADH-generating
      dehydrogenase involved in the formaldehyde oxidation pathway) could survive.
      These results indicated that FLD, but not FDH, is essential for growth of C.
      boidinii on methanol.

PMID- 12213917
TI  - Growth and killing of a Salmonella enterica serovar Typhimurium sifA mutant
      strain in the cytosol of different host cell lines.
AB  - Intracellular pathogens have developed different mechanisms which enable their
      survival and replication within the host cells. Some survive and replicate within
      a membrane-bound vacuole modified by the bacteria to support microbial growth
      (e.g. Salmonella enterica serovar Typhimurium), whereas others escape from the
      vacuole into the host cell cytosol, where they proliferate (e.g. Listeria
      monocytogenes). In this study a Salmonella strain carrying a mutation in sifA
      which is released from the vacuole was used to analyse Salmonella survival and
      replication within the cytosol of several cell lines. It was found that
      Salmonella replicates within the cytosol of epithelial cells at a higher rate
      than that achieved when replicating within the vacuole, but is defective for
      replication in the cytosol of fibroblasts or macrophages. Using an aroC purD
      double mutant strain which does not replicate within host cells, it was shown
      that Salmonella encounters a killing activity within the cytosol of macrophages.
      Furthermore, in vitro experiments using cytosol extracted from either infected or
      uninfected macrophages suggested that this activity is activated upon Salmonella
      infection.

PMID- 12213918
TI  - Active but nonculturable cells of Salmonella enterica serovar Typhimurium do not
      infect or colonize mice.
AB  - The possibility that nonculturable cells of a normally culturable bacterial
      pathogen may constitute a source or reservoir for infective disease was
      investigated. In multiple experiments and with careful attention to the
      statistical limitations of the assays used, Salmonella enterica serovar
      Typhimurium cells rendered nonculturable by carbon and nitrogen stress in the
      presence of chloramphenicol were administered orally and intraperitoneally to
      over 300 female BALB/c mice. Neither infection nor colonization was detected in
      these studies, even when active but nonculturable (ABNC) cells, as defined by the
      Kogure cell elongation assay, were present in the inoculum. Doses of ABNC cells
      exceeding the oral and intraperitoneal LD(50) values by 3.5 and 2 orders of
      magnitude, respectively, were administered. It was concluded that ABNC cells of
      the salmonella strains used could not be considered potentially infective and
      that their detection in samples from material being evaluated as a potential
      source or reservoir of infection by the Kogure test does not specifically
      represent an infective hazard.

PMID- 12213919
TI  - ClpP is involved in the stress response and degradation of misfolded proteins in
      Salmonella enterica serovar Typhimurium.
AB  - Components of the ATP-dependent Clp protease complex are found in a wide range of
      prokaryotic cells and they are often expressed as part of the cellular stress
      response. To investigate the physiological role of the proteolytic subunit, ClpP,
      in Salmonella enterica serovar Typhimurium (S. typhimurium) an in-frame deletion
      of the clpP gene was constructed. Growth experiments revealed that clpP is
      important for the ability of S. typhimurium to grow under various stressful
      conditions, such as low pH, elevated temperature and high salt concentrations.
      Since the stationary-phase sigma factor, RpoS, is a target of the Clp proteolytic
      complex, the effect of the clpP deletion in the absence of RpoS was examined; it
      was observed that growth of the S. typhimurium clpP mutant is affected in both an
      RpoS-dependent and an RpoS-independent manner. Analysis of the degradation of
      abnormal puromycyl-containing polypeptides showed that ClpP participates in the
      proteolysis of such proteins in S. typhimurium. These findings prompted an
      investigation of the growth of an Escherichia coli clpP mutant under various
      stress conditions. The growth of this E. coli mutant was affected by heat, salt
      and low pH, although not to the same extent as observed for the S. typhimurium
      clpP mutant. The results of this study indicate that the S. typhimurium clpP
      mutant is generally more sensitive to environmental stress than the E. coli clpP
      mutant and it is proposed that this is due to a reduced ability to degrade
      misfolded proteins generated under these conditions.

PMID- 12213920
TI  - Thermoregulated expression of virulence genes in enteropathogenic Escherichia
      coli.
AB  - Enteropathogenic Escherichia coli (EPEC) causes severe diarrhoea in young
      children. The locus of enterocyte effacement (LEE) pathogenicity island comprises
      a cluster of operons encoding a type III secretion system and related proteins
      that are associated with EPEC virulence. The LEE1 operon encodes Ler that
      positively regulates the LEE2, LEE3, LEE4, LEE5 and espG transcriptional units.
      The LEE operons are repressed at 27 degrees C and expressed at 37 degrees C. This
      paper describes a regulatory cascade of the thermoregulation of LEE operons. LEE1
      including ler is repressed by H-NS at 27 degrees C but not at 37 degrees C. In
      contrast, the expression of the LEE2, LEE3, LEE4, LEE5 and espG transcriptional
      units is repressed by H-NS at both 27 degrees C and 37 degrees C. Upon shifting
      the culture temperature from 27 degrees C to 37 degrees C, Ler is synthesized and
      in turn activates the expression of LEE2, LEE3, LEE4 and espG by releasing the H
      NS mediated repression. In the case of LEE5, Ler acts both by alleviating the H
      NS mediated repression and by an additional mechanism, as yet to be defined.

PMID- 12213921
TI  - Vaginal Escherichia coli share common virulence factor profiles, serotypes and
      phylogeny with other extraintestinal E. coli.
AB  - Characteristics of Escherichia coli residing in the vagina and their role in
      extraintestinal infections are largely unknown. In this study, 88 vaginal E. coli
      (VEC) isolates from Japanese women were characterized by extraintestinal
      virulence factor (VF) profiling, O:H serotyping and phylogenetic analysis. The
      prevalence of papC, hlyA, cnfI, PAI, ibeA and K1 antigen among the VEC strains
      were 45, 22, 19, 78, 32 and 44%, respectively. Phylogenetic analysis identified
      76, 16 and 8% of the VEC strains in groups B2, D and A, respectively. The VEC
      strains were distributed into 31 serotypes, including 8 common serotypes
      (O1:K1:H1, O1:K1:H7, O2:K1:H7, O4:H5, O6:H1, O18ac:K1:H7, O25:H1 and O75:HNM)
      that were identified in three or more isolates. Comparative analysis with 61
      stool isolates from healthy Japanese men and women, and with data from previous
      studies, revealed that, although some geographical specificities do exist, the
      VEC strains shared common VF profiles, O:K:H serotypes and phylogeny with
      uropathogenic E. coli and E. coli of neonatal septicaemia and meningitis. This
      study provides additional evidence for a link among extraintestinal E. coli,
      supporting the concept that the VEC are a reservoir along the 'faecal-vaginal
      urinary/neonatal' course of transmission in the extraintestinal E. coli
      infections.

PMID- 12213922
TI  - Activation of the transcription factor NF-kappaB by Campylobacter jejuni.
AB  - Campylobacter jejuni is a food-borne pathogen responsible for infectious
      enterocolitis. The early-response transcription factor NF-kappa B triggers the
      expression of genes associated with cellular immune and inflammatory responses.
      Co-incubation of HeLa cells with viable C. jejuni leads to the activation of the
      transcription factor NF-kappa B as determined by specific induction of a cellular
      luciferase-based reporter. Boiled cell-free extracts of C. jejuni are also potent
      dose-dependent stimulators of NF-kappa B-dependent transcription, the levels of
      which can reach up to 1000-fold as compared with independent controls. Using both
      cultured HeLa cells and human colonic epithelial (HCA-7) cells, the activation of
      NF-kappa B by C. jejuni boiled extract has been monitored through the degradation
      of IKB alpha and DNA binding of the nuclear translocated p50/p65 heterodimer of
      NF-kappa B. These events are co-ordinated with elaboration of the pro
      inflammatory cytokine interleukin-8. Fractionation of the boiled C. jejuni
      extract suggests that the majority of the bioactive component has a molecular
      mass of 3 kDa or less, which is insensitive to proteinase K treatment.

PMID- 12213923
TI  - Comparative proteomics of Staphylococcus aureus and the response of methicillin
      resistant and methicillin-sensitive strains to Triton X-100.
AB  - Proteomics is a powerful tool for analysing differences in gene expression
      between bacterial strains with alternate phenotypes. Staphylococcus aureus
      strains are grouped on the basis of their sensitivity to methicillin. Two
      dimensional gel electrophoresis was combined with MS to compare the protein
      profiles of S. aureus strains COL (methicillin-resistant) and 8325 (methicillin
      sensitive). Reference mapping via this approach identified 377 proteins that
      corresponded to 266 distinct ORFs. Amongst these identified proteins were 14
      potential virulence factors. The production of 41 'hypothetical' proteins was
      confirmed, and eight of these appeared to be unique to S. aureus. Strain COL
      displayed 12 protein spots, which included alkaline-shock protein 23 (Asp23) and
      cold-shock proteins CspABC, which either were not present in strain 8325 or were
      present at a significantly lower intensity in this strain. Comparative maps were
      used to characterize the S. aureus response to treatment with Triton X-100 (TX
      100), a detergent that has been shown to reduce methicillin resistance
      independently of an interaction with the mecA-encoded penicillin-binding protein
      2a. In response to growth of the bacteria in the presence of TX-100, 44 protein
      spots showed altered levels of abundance, and 11 of these spots were found only
      in COL. The products of genes regulated by sigma(B) (the alternative sigma
      factor), including Asp23 and three proteins of unknown function, and SarA (a
      regulator of virulence genes) were shown to be present at significantly altered
      levels. SarA production was induced in TX-100-treated cultures. A protein of the
      sigma(B) operon, RsbV, was only detected in COL and its production was down
      regulated in COL when the strain was treated with TX-100, whereas RsbW was
      present at reduced levels in both strains. Upon growth of both strains in the
      presence of TX-100, no effects on the production of the essential methicillin
      resistance factor FemA were detected, whereas phosphoglucosamine mutase (GlmM)
      production was reduced in COL alone. This study suggests that proteins of the
      sigma(B) and sarA regulons, as well as other factors, are involved in methicillin
      resistance in S. aureus.

PMID- 12213924
TI  - Characterization of the xylose-transporting properties of yeast hexose
      transporters and their influence on xylose utilization.
AB  - For an economically feasible production of ethanol from plant biomass by
      microbial cells, the fermentation of xylose is important. As xylose uptake might
      be a limiting step for xylose fermentation by recombinant xylose-utilizing
      Saccharomyces cerevisiae cells a study of xylose uptake was performed. After
      deletion of all of the 18 hexose-transporter genes, the ability of the cells to
      take up and to grow on xylose was lost. Reintroduction of individual hexose
      transporter genes in this strain revealed that at intermediate xylose
      concentrations the yeast high- and intermediate-affinity transporters Hxt4, Hxt5,
      Hxt7 and Gal2 are important xylose-transporting proteins. Several heterologous
      monosaccharide transporters from bacteria and plant cells did not confer
      sufficient uptake activity to restore growth on xylose. Overexpression of the
      xylose-transporting proteins in a xylose-utilizing PUA yeast strain did not
      result in faster growth on xylose under aerobic conditions nor did it enhance the
      xylose fermentation rate under anaerobic conditions. The results of this study
      suggest that xylose uptake does not determine the xylose flux under the
      conditions and in the yeast strains investigated.

PMID- 12213925
TI  - The antiapoptotic protein Bcl-x(L) prevents the cytotoxic effect of Bax, but not
      Bax-induced formation of reactive oxygen species, in Kluyveromyces lactis.
AB  - The murine proapoptotic protein Bax was expressed in Kluyveromyces lactis to
      investigate its effect on cell survival and production of reactive oxygen species
      (ROS). Bax expression decreased the number of cells capable of growing and
      forming colonies, and it increased the number of cells producing ROS, as detected
      by both dihydrorhodamine 123 fluorescence and the intracellular content of SH
      groups. Mutation in the beta-subunit of F(1)-ATPase, or mitochondrial deficiency
      resulting from deletion of mtDNA (rho(0) mutant), increased the sensitivity to
      Bax, indicating that Bax cytotoxicity does not require mitochondrial respiratory
      chain functions. The antiapoptotic protein Bcl-x(L), when co-expressed with Bax,
      localized to the mitochondria and prevented Bax cytotoxicity. However, this co
      expression did not prevent the production of ROS. These data suggest that in K.
      lactis cells expressing Bax, ROS are not the sine qua non of cell death and that
      the antiapoptotic function of Bcl-x(L) is not limited to its antioxidant
      property.

PMID- 12213926
TI  - Suppression of fruit-body formation by constitutively active G-protein alpha
      subunits ScGP-A and ScGP-C in the homobasidiomycete Schizophyllum commune.
AB  - The heterotrimeric G-protein alpha-subunit family plays multiple roles in
      eukaryotic cells, such as the regulation of growth and development, of
      pathogenicity and of the transmission of pheromone stimulation. In the
      homobasidiomycete Schizophyllum commune, some genes encoding heterotrimeric G
      protein alpha-subunits (SCGPalpha1, SCGPalpha2, ScGP-A, ScGP-B and ScGP-C) have
      been reported. In this study, constitutively active mutants of ScGP-A, ScGP-B and
      ScGP-C were generated by site-directed mutagenesis and introduced into the S.
      commune monokaryon strain to investigate the function of each gene. Northern
      analysis showed that the mutated genes were strongly expressed when compared with
      endogenous G-proteins in many clones. Upon macroscopic examination, some
      transformed clones expressing ScGP-A (Q207R) and ScGP-C (Q204R) mutant genes
      exhibited a slight suppression of aerial-hyphae formation in the monokaryon
      strain. In contrast to the slight suppression of aerial-hyphae formation in the
      monokaryon, most clones expressing mutated ScGP-A or ScGP-C genes failed to form
      fruit-bodies in the dikaryon strain. This observation indicated that ScGP-A and
      ScGP-C played a role in suppressing fruit-body formation in the dikaryon.
      Furthermore, these phenotypes were similar to the phenotype of the thn mutant in
      S. commune to some extent. Since the thn-1 gene encodes a putative regulator of
      the G-protein signalling protein (RGS), ScGP-A and ScGP-C might be targets of thn
      1.

PMID- 12213927
TI  - Compensatory expression of five chitin synthase genes, a response to stress
      stimuli, in Wangiella (Exophiala) dermatitidis, a melanized fungal pathogen of
      humans.
AB  - Numerous chitin synthase structural (CHS) genes have been identified in fungi,
      and usually there are several CHS genes per species. Compensatory expression of
      one CHS gene in response to defects in other CHS genes has not been reported.
      Five chitin synthase structural (WdCHS) genes have been identified in the
      melanized human pathogen Wangiella dermatitidis: WdCHS1, WdCHS2, WdCHS3, WdCHS4
      and WdCHS5. This study showed that increased WdCHS expression existed as a
      compensatory mechanism in response to stress induced by chitin synthase gene
      disruptions, or by exposure of the wild-type or two temperature-sensitive
      morphological mutants, for short or long periods, to 37 degrees C. In general,
      the compensatory responses varied with each WdCHS gene, and in accordance with
      the hypothesized functions of the chitin synthase (WdChsp) encoded. It is
      suggested that these compensatory responses indicate that WdCHS gene
      transcription in W. dermatitidis functions as part of a cell-wall integrity
      pathway in a manner similar to that recently described for Saccharomyces
      cerevisiae.

PMID- 12213928
TI  - Characterization of a cell-wall acid phosphatase (PhoAp) in Aspergillus
      fumigatus.
AB  - In the filamentous fungus Aspergillus fumigatus, the vast majority of the cell
      wall-associated proteins are secreted proteins that are in transit in the cell
      wall. These proteins can be solubilized by detergents and reducing agents.
      Incubation of a SDS/beta-mercaptoethanol-treated cell-wall extract with various
      recombinant enzymes that hydrolyse cell-wall polysaccharides resulted in the
      release of a unique protein in minute amounts only after incubation of the cell
      wall in the presence of 1,3-beta-glucanase. Sequence analysis and biochemical
      studies showed that this glycoprotein, with an apparent molecular mass of 80 kDa,
      was an acid phosphatase (PhoAp) that was active on both phosphate monoesters and
      phosphate diesters. PhoAp is a glycosylphosphatidylinositol-anchored protein that
      was recovered in the culture filtrate and cell-wall fraction of A. fumigatus
      after cleavage of its anchor. It is also a phosphate-repressible acid
      phosphatase. The absence of PhoAp from a phosphate-rich medium was not associated
      with a reduction in fungal growth, indicating that this cell-wall-associated
      protein does not play a role in the morphogenesis of A. fumigatus.

PMID- 12213930
TI  - Molecular characterization of functional modules of plasmid pWKS1 of Paracoccus
      pantotrophus DSM 11072.
AB  - The complete nucleotide sequence of the small, cryptic plasmid pWKS1 (2697 bp) of
      Paracoccus pantotrophus DSM 11072 was determined. The G+C content of the sequence
      of this plasmid was 62 mol%. Analysis revealed that over 80% of the plasmid
      genome was covered by two ORFs, ORF1 and ORF2, which were capable of encoding
      putative peptides of 44.1 and 37.8 kDa, respectively. Mutational analysis showed
      that ORF2 was crucial for plasmid replication. The translational product of ORF2
      shared local homologies with replication proteins of several theta-replicating
      lactococcal plasmids, as well as with the Rep proteins of plasmids residing in
      Gram-negative hosts. An A+T-rich region, located upstream of the rep gene and
      containing three tandemly repeated 21 bp long iteron-like sequences, served as
      the origin of replication (oriV). ORF1 encoded a putative mobilization protein
      with similarities to mobilization proteins (Mob) from the broad-host-range
      plasmid pBBR1 and plasmids of Gram-positive bacteria. A plasmid bearing the MOB
      module of pWKS1 (the mob gene and the oriT sequence) could be mobilized for
      transfer (by IncP RP4 transfer apparatus) at low frequency between different
      strains of Escherichia coli. MOB modules of pWKS1 and pBBR1 were functionally
      complementary to each other. Hybridization analysis revealed that only plasmid
      pSOV1 (6.5 kb), among all of the paracoccal plasmids identified so far, carries
      sequences related to pWKS1. Plasmid pWKS1 could replicate in 10 species of
      Paracoccus and in Agrobacterium tumefaciens, Rhizobium leguminosarum and
      Rhodobacter sphaeroides, but it could not replicate in E. coli.

PMID- 12213931
TI  - Molecular characterization of an operon, cueAR, encoding a putative P1-type
      ATPase and a MerR-type regulatory protein involved in copper homeostasis in
      Pseudomonas putida.
AB  - The authors have characterized a chromosomally localized two-gene operon, cueAR,
      which encodes a putative P1-type ATPase, CueA, and a MerR-type metalloregulatory
      protein, CueR, in Pseudomonas putida PNL-MK25. Disruption of cueAR by the
      insertion of mini-Tn5::gfp into the wild-type strain led to a mutant strain with
      a sixfold reduction in its tolerance to copper; however, the tolerance of this
      mutant strain to the other seven related transition metals tested was not
      affected. The sensitivity of the mutant strain was attributed to a higher level
      of accumulation of intracellular copper, suggesting the involvement of CueA in
      copper export. Insertion of the cloned cueAR operon into the copper-sensitive
      mutant strain fully restored its tolerance to copper. cueA::gfp expression
      studies confirmed that the cueAR operon was transcriptionally regulated by copper
      and CueR. Studies done on the mutant strain complemented with cueR and cueA
      revealed partial functional redundancy of cueA and cueR, respectively, in copper
      tolerance. Thus, the results of this study clearly suggest the involvement of
      cueAR in copper homeostasis in P. putida.

PMID- 12213929
TI  - Molecular phylogeny of type II methane-oxidizing bacteria isolated from various
      environments.
AB  - Type II methane-oxidizing bacteria (MOB) were isolated from diverse environments,
      including rice paddies, pristine and polluted freshwaters and sediments, mangrove
      roots, upland soils, brackish water ecosystems, moors, oil wells, water
      purification systems and livestock manure. Isolates were identified based on
      morphological traits as either Methylocystis spp., Methylosinus sporium or
      Methylosinus trichosporium. Molecular phylogenies were constructed based on
      nearly complete 16S rRNA gene sequences, and on partial sequences of genes
      encoding PmoA (a subunit of particulate methane monooxygenase), MxaF (a subunit
      of methanol dehydrogenase) and MmoX (a subunit of soluble methane monooxygenase).
      The maximum pairwise 16S rDNA difference between isolates was 4.2%, and
      considerable variability was evident within the Methylocystis (maximum difference
      3.6%). Due to this variability, some of the published 'specific' oligonucleotide
      primers for type II MOB exhibit multiple mismatches with gene sequences from some
      isolates. The phylogenetic tree constructed from pmoA gene sequences closely
      mirrored that constructed from 16S rDNA sequences, and both supported the
      presently accepted taxonomy of type II MOB. Contrary to previously published
      phylogenetic trees, morphologically distinguishable species were generally
      monophyletic based on pmoA or 16S rRNA gene sequences. This was not true for
      phylogenies constructed from mmoX and mxaF gene sequences. The phylogeny of mxaF
      gene sequences suggested that horizontal transfer of this gene may have occurred
      across type II MOB species. Soluble methane monooxygenase could not be detected
      in many Methylocystis strains either by an enzyme activity test (oxidation of
      naphthalene) or by PCR-based amplification of an mmoX gene.

PMID- 12213932
TI  - Molecular cloning and characterization of the ferric hydroxamate uptake (fhu)
      operon in Actinobacillus pleuropneumoniae.
AB  - The bacterium Actinobacillus pleuropneumoniae, a swine pathogen, utilizes
      ferrichrome as an iron source. This study details the molecular cloning and
      sequencing of the genes involved in the uptake of this hydroxamate siderophore.
      Four ferric hydroxamate uptake (fhu) genes, fhuC, fhuD, fhuB and fhuA, were
      identified in a single operon, and these were found to encode proteins homologous
      to proteins of the fhu systems of several bacteria, including Escherichia coli.
      The fhuA gene encodes the 77 kDa outer-membrane protein (OMP) FhuA, the receptor
      for ferrichrome. FhuD is the 35.6 kDa periplasmic protein responsible for the
      translocation of ferric hydroxamate from the outer to the inner membrane. FhuC
      (28.5 kDa) and FhuB (69.4 kDa) are cytoplasmic-membrane-associated proteins that
      are components of an ABC transporter which internalizes the ferric hydroxamate.
      Reference strains of A. pleuropneumoniae that represented serotypes 1 to 12 of
      this organism all tested positive for the four fhu genes. When A.
      pleuropneumoniae FhuA was affinity-tagged with hexahistidine at its amino
      terminus and expressed in an E. coli host, the recombinant protein reacted with
      an mAb against E. coli FhuA, as well as with a polyclonal pig serum raised
      against an A. pleuropneumoniae infection. Hence, the authors conclude that fhuA
      is expressed in vivo by A. pleuropneumoniae. Three-dimensional modelling of the
      OMP FhuA was achieved by threading it to the X-ray crystallographic structure of
      the homologous protein in E. coli. FhuA from A. pleuropneumoniae was found to
      have the same overall fold as its E. coli homologue, i.e. it possesses an N
      terminal cork domain followed by a C-terminal beta-barrel domain and displays 11
      extracellular loops and 10 periplasmic turns.

PMID- 12213933
TI  - Assimilatory detoxification of herbicides by Delftia acidovorans MC1: induction
      of two chlorocatechol 1,2-dioxygenases as a response to chemostress.
AB  - Proteome analysis of bacteria that can detoxify harmful organic compounds enables
      the discovery of enzymes involved in the biodegradation of these substances and
      proteins that protect the cell against poisoning. Exposure of Delftia acidovorans
      MC1 to 2,4-dichlorophenoxypropionic acid and its metabolites 2,4-dichlorophenol
      and 3,5-dichlorocatechol during growth on pyruvate as a source of carbon and
      energy induced several proteins. Contrary to the general hypothesis that
      lipophilic or reactive compounds induce heat shock or oxidative stress proteins,
      no induction of the GroEL, DnaK and AhpC proteins that were used as markers for
      the induction of heat shock and oxidative stress responses was observed. However,
      two chlorocatechol1,2-dioxygenases, identified by amino terminal sequence
      analysis, were induced. Both enzymes catalyse the conversion of 3,5
      dichlorocatechol to 2,4-dichloro-cis,cis-muconate indicating that biodegradation
      is a major mechanism of resistance in the detoxifying bacterium D. acidovorans
      MC1.

PMID- 12213934
TI  - The apparent clock-like evolution of Escherichia coli in glucose-limited
      chemostats is reproducible at large but not at small population sizes and can be
      explained with Monod kinetics.
AB  - To follow and model evolution of a microbial population in the chemostat,
      parameters are needed that give an indication of the absolute extent of evolution
      at a high resolution of time. In this study the evolution of the maximum specific
      growth rate ( micro (max)) and the residual glucose concentration was followed
      for populations of Escherichia coli K-12 under glucose-limited conditions at
      dilution rates of 0.1 x h(-1), 0.3 x h(-1) and 0.53 x h(-1) during 500-700 h in
      continuous culture. Whereas micro (max) improved only during the initial 150 h,
      the residual glucose concentration decreased constantly during 500 h of
      cultivation and therefore served as a convenient parameter to monitor the
      evolution of a population at a high time resolution with respect to its affinity
      for the growth-limiting substrate. The evolution of residual glucose
      concentrations was reproducible in independent chemostats with a population size
      of 10(11) cells, whereas no reproducibility was found in chemostats containing
      10(7) cells. A model based on Monod kinetics assuming successive take-overs of
      mutants with improved kinetic parameters (primarily K(s)) was able to simulate
      the experimentally observed evolution of residual glucose concentrations. Similar
      values for the increase in glucose affinity of mutant phenotypes (K(s(mutant))
      approximately equal 0.6 x K(s(parent))) and similar mutation rates per cell per
      generation leading to these mutant phenotypes (1-5 x1 0(-7)) were estimated in
      silico for all dilution rates. The model predicts a maximum rate of evolution at
      a dilution rate slightly below micro (max)/2. With increasing and decreasing
      dilution rates the evolution slows down, which also explains why in special cases
      a selection-driven evolution can exhibit apparent clock-like behaviour. The
      glucose affinity for WT cells was dependent on the dilution rate with highest
      values at dilution rates around micro (max)/2. Below 0.3 x h(-1) poorer affinity
      was mainly due to the effects of rpoS.

PMID- 12213935
TI  - Mutations in KaiA, a clock protein, extend the period of circadian rhythm in the
      cyanobacterium Synechococcus elongatus PCC 7942.
AB  - KaiA KaiB and KaiC are essential circadian clock proteins in the unicellular
      cyanobacterium Synechococcus elongatus PCC 7942. KaiA protein activates
      transcription of the kaiBC operon, which is believed to be a crucial step in the
      oscillating feedback loop of cyanobacteria. In this study, approximately
      approximately 400 mutations were introduced into kaiA by PCR-based mutagenesis,
      and rhythmic phenotypes of these mutants were studied by a bioluminescence
      reporter. In contrast to mutations in KaiB or KaiC, the vast majority of KaiA
      mutations extended the period and only rarely shortened it. The period could be
      extended to 35 h without lowering the mean or peak levels of kaiBC expression.
      However, several mutations resulted in low-amplitude oscillations or arrhythmia,
      which were accompanied by lowered kaiBC transcription. These results imply that
      the KaiA protein can change the period length of the circadian rhythm directly
      (through an unknown biochemical mechanism) or indirectly (by lowering kaiBC
      expression). Specific mutations of KaiA were identified in 34 mutants. While
      mutations mapped to various locations of the KaiA sequence, two clusters of
      period-altering mutations were found. This suggested that these regions are
      important domains of the KaiA protein for defining the period length. On the
      other hand, different sequences within KaiA to which arrhythmic mutations were
      mapped are important to enhance kaiBC expression.

PMID- 12213936
TI  - Disruption analysis of DR1420 and/or DR1758 in the extremely radioresistant
      bacterium Deinococcus radiodurans.
AB  - The extremely radioresistant bacterium Deinococcus radiodurans encodes two genes
      that are homologous to those involved in bacterial lysine biosynthesis. In lysine
      biosynthesis, these genes are involved in the aminoadipate pathway and the
      diaminopimelate (DAP) pathway. DR1420 is homologous to lysZ, which is essential
      for bacterial lysine biosynthesis via the aminoadipate pathway, and DR1758 is
      homologous to lysA, which is essential for lysine biosynthesis via the DAP
      pathway. In this study, DR1420 and/or DR1758 were disrupted. Each disruptant of
      DR1420 and DR1758, and of DR1420 or DR1758 grew in a minimal medium, as did the
      wild-type. These results show that D. radiodurans performs lysine biosynthesis in
      a unique way.

PMID- 12213937
TI  - Microbial degradation of polyhydroxyalkanoates.
AB  - Polyesters such as poly(3-hydroxybutyrate) (PHB) or other polyhydroxyalkanoates
      (PHA) have attracted commercial and academic interest as new biodegradable
      materials. The ability to degrade PHA is widely distributed among bacteria and
      fungi and depends on the secretion of specific extracellular PHA depolymerases (e
      PHA depolymerases), which are carboxyesterases (EC 3.1.1.75 and EC 3.1.1.76), and
      on the physical state of the polymer (amorphous or crystalline). This
      contribution provides a summary of the biochemical and molecular biological
      characteristics of e-PHA depolymerases and focuses on the intracellular
      mobilization of storage PHA by intracellular PHA depolymerases (i-PHA
      depolymerases) of PHA-accumulating bacteria. The importance of different assay
      systems for PHA depolymerase activity is also discussed.

PMID- 12213938
TI  - Growing old: metabolic control and yeast aging.
AB  - The metabolic characteristics of a yeast cell determine its life span. Depending
      on conditions, stress resistance can have either a salutary or a deleterious
      effect on longevity. Gene dysregulation increases with age, and countering it
      increases life span. These three determinants of yeast longevity may be
      interrelated, and they are joined by a potential fourth, genetic stability. These
      factors can also operate in phylogenetically diverse species. Adult longevity
      seems to borrow features from the genetic programs of dormancy to provide the
      metabolic and stress resistance resources necessary for extended survival. Both
      compensatory and preventive mechanisms determine life span, while epigenetic
      factors and the element of chance contribute to the role that genes and
      environment play in aging.

PMID- 12213939
TI  - Images in clinical medicine. Severe abdominal pain in a girl.

PMID- 12213940
TI  - Physical inactivity among young people.

PMID- 12213941
TI  - Decline in physical activity in black girls and white girls during adolescence.
AB  - BACKGROUND: Physical activity declines during adolescence, but the underlying
      reasons remain unknown. METHODS: We prospectively followed 1213 black girls and
      1166 white girls enrolled in the National Heart, Lung, and Blood Institute Growth
      and Health Study from the ages of 9 or 10 to the ages of 18 or 19 years. We used
      a validated questionnaire to measure leisure-time physical activity on the basis
      of metabolic equivalents (MET) for reported activities and their frequency in MET
      times per week; a higher score indicated greater activity. RESULTS: The
      respective median activity scores for black girls and white girls were 27.3 and
      30.8 MET-times per week at base line and declined to 0 and 11.0 by year 10 of the
      study (a 100 percent decline for black girls and a 64 percent decline for white
      girls, P<0.001). By the age of 16 or 17 years, 56 percent of the black girls and
      31 percent of the white girls reported no habitual leisure-time activity. Lower
      levels of parental education were associated with greater decline in activity for
      white girls at both younger ages (P<0.001) and older ages (P=0.005); for black
      girls, this association was seen only at the older ages (P=0.04). Pregnancy was
      associated with decline in activity among black girls (P<0.001) but not among
      white girls, whereas cigarette smoking was associated with decline in activity
      among white girls (P<0.001). A higher body-mass index was associated with greater
      decline in activity among girls of both races (P< or =0.05). CONCLUSIONS:
      Substantial declines in physical activity occur during adolescence in girls and
      are greater in black girls than in white girls. Some determinants of this
      decline, such as higher body-mass index, pregnancy, and smoking, may be
      modifiable.

PMID- 12213942
TI  - Walking compared with vigorous exercise for the prevention of cardiovascular
      events in women.
AB  - BACKGROUND: The role of walking, as compared with vigorous exercise, in the
      prevention of cardiovascular disease remains controversial. Data for women who
      are members of minority racial or ethnic groups are particularly sparse. METHODS:
      We prospectively examined the total physical-activity score, walking, vigorous
      exercise, and hours spent sitting as predictors of the incidence of coronary
      events and total cardiovascular events among 73,743 postmenopausal women 50 to 79
      years of age in the Women's Health Initiative Observational Study. At base line,
      participants were free of diagnosed cardiovascular disease and cancer, and all
      participants completed detailed questionnaires about physical activity. We
      documented 345 newly diagnosed cases of coronary heart disease and 1551 total
      cardiovascular events. RESULTS: An increasing physical-activity score had a
      strong, graded, inverse association with the risk of both coronary events and
      total cardiovascular events. There were similar findings among white women and
      black women. Women in increasing quintiles of energy expenditure measured in
      metabolic equivalents (the MET score) had age-adjusted relative risks of coronary
      events of 1.00, 0.73, 0.69, 0.68, and 0.47, respectively (P for trend, <0.001).
      In multivariate analyses, the inverse gradient between the total MET score and
      the risk of cardiovascular events remained strong (adjusted relative risks for
      increasing quintiles, 1.00, 0.89, 0.81, 0.78, and 0.72, respectively; P for trend
      <0.001). Walking and vigorous exercise were associated with similar risk
      reductions, and the results did not vary substantially according to race, age, or
      body-mass index. A brisker walking pace and fewer hours spent sitting daily also
      predicted lower risk. CONCLUSIONS: These prospective data indicate that both
      walking and vigorous exercise are associated with substantial reductions in the
      incidence of cardiovascular events among postmenopausal women, irrespective of
      race or ethnic group, age, and body-mass index. Prolonged sitting predicts
      increased cardiovascular risk.

PMID- 12213943
TI  - Use of the low-molecular-weight heparin reviparin to prevent deep-vein thrombosis
      after leg injury requiring immobilization.
AB  - BACKGROUND: Deep-vein thrombosis is a well-recognized complication after trauma
      to the legs and subsequent immobilization, but there are no generally accepted
      approaches to preventing this complication. METHODS: We performed a prospective,
      double-blind, placebo-controlled trial to evaluate the efficacy and safety of
      subcutaneous reviparin (1750 anti-Xa units given once daily) in 440 patients who
      required immobilization in a plaster cast or brace for at least five weeks after
      a leg fracture or rupture of the Achilles tendon. The study drug was given
      throughout the period of immobilization. Venography of the injured leg was
      performed within one week after removal of the plaster cast or brace, or earlier
      if there were symptoms suggesting deep-vein thrombosis. RESULTS: Data on efficacy
      and end points were available for 371 patients. Deep-vein thrombosis was
      diagnosed in 17 of the 183 patients randomly assigned to receive reviparin (9
      percent) and in 35 of the 188 patients randomly assigned to receive placebo (19
      percent) (odds ratio, 0.45; 95 percent confidence interval, 0.24 to 0.82). Most
      of the thromboses were distal (14 in the reviparin group and 25 in the placebo
      group). There were two cases of pulmonary embolism, both in patients in the
      placebo group who also had proximal deep-vein thrombosis. There were no
      differences between the two groups with respect to bleeding or other adverse
      events. CONCLUSIONS: Deep-vein thrombosis is common in persons with leg injury
      requiring prolonged immobilization. Reviparin given once daily appears to be
      effective and safe in reducing the risk of this complication.

PMID- 12213944
TI  - A patient with HIV-1 superinfection.

PMID- 12213945
TI  - Images in clinical medicine. Sclerosing peritonitis during continuous ambulatory
      peritoneal dialysis.

PMID- 12213946
TI  - IgA nephropathy.

PMID- 12213947
TI  - Clinical problem-solving. Out of Africa.

PMID- 12213948
TI  - Additional steps for cardiovascular health.

PMID- 12213949
TI  - HIV-1 superinfection--a word of caution.

PMID- 12213950
TI  - Nonfinancial conflicts of interest in research.

PMID- 12213951
TI  - Estrogen-receptor polymorphism and hormone-replacement therapy.

PMID- 12213952
TI  - Development of Kaposi's sarcoma at the site of a biopsy.

PMID- 12213953
TI  - Treatment of migraine.

PMID- 12213954
TI  - Schistosomiasis.

PMID- 12213955
TI  - Nonalcoholic fatty liver disease.

PMID- 12213956
TI  - Mechanical extraction of a basilar-artery embolus with the use of flow reversal
      and a microbasket.

PMID- 12213957
TI  - Type III secretion systems and the evolution of mutualistic endosymbiosis.
AB  - The view that parasites can develop cooperative symbiotic relationships with
      their hosts is both appealing and widely held; however, there is no molecular
      genetic evidence of such a transition. Here we demonstrate that a mutualistic
      bacterial endosymbiont of grain weevils maintains and expresses inv/spa genes
      encoding a type III secretion system homologous to that used for invasion by
      bacterial pathogens. Phylogenetic analyses indicate that inv/spa genes were
      present in presymbiotic ancestors of the weevil endosymbionts, occurring at least
      50 million years ago. The function of inv/spa genes in maintaining symbiosis is
      demonstrated by the up-regulation of their expression under both in vivo and in
      vitro conditions that coincide with host cell invasion.

PMID- 12213958
TI  - Isolation of an Arabidopsis mutant lacking vitamin E and identification of a
      cyclase essential for all tocopherol biosynthesis.
AB  - Tocopherol (vitamin E) is a plant chloroplast lipid presumed to be involved in
      the response to oxidative stress. A tocopherol-deficient mutant (vte1) was
      isolated from Arabidopsis thaliana by using a TLC-based screening approach.
      Mutant plants lacked all four tocopherol forms and were deficient in tocopherol
      cyclase activity. Genetic mapping of vte1 and a genomics-based approach led to
      the identification of the ORF At4g32770 as a candidate gene for tocopherol
      cyclase. In vte1, At4g32770 contains a splicing site mutation and the
      corresponding mRNA expression is reduced. Expression of VTE1 in Escherichia coli
      resulted in the production of a protein with high tocopherol cyclase and
      tocotrienol cyclase activity. The VTE1 sequence shows no similarities to genes
      with known function, but is similar to that of SXD1, a gene that was recently
      isolated based on the availability of the sucrose export defective1 maize mutant
      (sxd1). Growth of the vte1 mutant, chlorophyll content, and photosynthetic
      quantum yield were similar to wild type under optimal growth conditions.
      Therefore, absence of tocopherol has no large impact on photosynthesis or plant
      viability, suggesting that other antioxidants can compensate for the loss of
      tocopherol. During photo-oxidative stress, chlorophyll content and photosynthetic
      quantum yield were slightly reduced in vte1 as compared with wild type indicating
      a potential role for tocopherol in maintaining an optimal photosynthesis rate
      under high-light stress.

PMID- 12213959
TI  - Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo
      biloba extract EGb761.
AB  - Standardized extract from the leaves of the Ginkgo biloba tree, labeled EGb761,
      has been used in clinical trials for its beneficial effects on brain functions,
      particularly in connection with age-related dementias and Alzheimer's disease
      (AD). Substantial experimental evidence indicates that EGb761 protects against
      neuronal damage from a variety of insults, but its cellular and molecular
      mechanisms remain unknown. Using a neuroblastoma cell line stably expressing an
      AD-associated double mutation, we report that EGb761 inhibits formation of
      amyloid-beta (Abeta) fibrils, which are the diagnostic, and possibly causative,
      feature of AD. The decreased Abeta fibrillogenesis in the presence of EGb761 was
      observed both in the conditioned medium of this Abeta-secreting cell line and in
      solution in vitro. In the cells, EGb761 significantly attenuated mitochondrion
      initiated apoptosis and decreased the activity of caspase 3, a key enzyme in the
      apoptosis cell-signaling cascade. These results suggest that (i) neuronal damage
      in AD might be due to two factors: a direct Abeta toxicity and the apoptosis
      initiated by the mitochondria; and (ii) multiple cellular and molecular
      neuroprotective mechanisms, including attenuation of apoptosis and direct
      inhibition of Abeta aggregation, underlie the neuroprotective effects of EGb761.

PMID- 12213960
TI  - Multiple thyroid hormone-induced muscle growth and death programs during
      metamorphosis in Xenopus laevis.
AB  - Xenopus laevis tadpole tails contain fast muscle fibers oriented in chevrons and
      two pairs of slow muscle "cords" along the length of the tail. When tail
      resorption is inhibited by a number of different treatments, fast muscle but not
      the slow cord muscle still is lost, demonstrating that the fast tail muscle is a
      direct target of the thyroid hormone-induced death program. Expression of a
      dominant negative form of the thyroid hormone receptor (TRDNalpha) was restricted
      to tadpole muscle by means of a muscle-specific promoter. Even though the
      transgene protects fast tail muscle from thyroid hormone (TH)-induced death, the
      tail shortens, and the distal muscle chevrons at the tail tip are degraded. This
      default pathway for muscle death is probably caused by the action of proteolytic
      enzymes secreted by neighboring fibroblasts. Non-muscle tissues that are
      sensitive to TH, such as the fibroblasts, are not protected by the transgene when
      it is expressed solely in muscle. If allowed to develop to metamorphosis, these
      transgenic animals die at the climax of metamorphosis before tail resorption has
      begun. Their limbs have very little muscle even though the rest of limb
      morphology is normal. Thus, fast tail muscle and limb muscle have their own cell
      autonomous death and growth programs, respectively, that are independent of the
      fate of the other neighboring cell types. In contrast, death of the slow muscle
      is controlled by the other cell types of the tail.

PMID- 12213961
TI  - STAT4 serine phosphorylation is critical for IL-12-induced IFN-gamma production
      but not for cell proliferation.
AB  - T helper 1 (T(H)1) differentiation and IFN-gamma production are crucial in cell
      mediated immune responses. IL-12 is an important regulator of this process and
      mediates its effects through signal transducer and activator of transcription 4
      (STAT4). IFN-gamma production is also regulated by the p38 mitogen-activated
      kinase pathway, although the mechanisms are ill-defined. We show here that GADD45
      beta and GADD45-gamma can induce STAT4 S721 phosphorylation via the MKK6/p38
      pathway. Thus, STAT4 could be a target that accounts for the defects in cell
      mediated immunity associated with perturbations in the p38 pathway. To
      investigate the biological significance of STAT4 S721 phosphorylation, we
      reconstituted primary spleen cells from STAT4-deficient mice with wild-type and
      mutated STAT4, by using a retroviral gene transduction. We demonstrated that
      expression of wild-type STAT4, but not the S721A mutant, restored normal T(H)1
      differentiation and IFN-gamma synthesis. The inability of STAT4 S721 to restore
      IFN-gamma production was not caused by decreased IL-12R expression because the
      STAT4 S721 mutant also failed to restore IFN-gamma production in STAT4-deficient
      IL-12Rbeta2 transgenic cells. Importantly, STAT4 S721A-transduced cells showed
      normal proliferative response to IL-12, illustrating that serine phosphorylation
      is not required for IL-12-induced proliferation. Additionally, the results imply
      the existence of STAT4 serine phosphorylation-dependent and -independent target
      genes. We conclude that phosphorylation of STAT4 on both tyrosine and serine
      residues is important in promoting normal T(H)1 differentiation and IFN-gamma
      secretion.

PMID- 12213962
TI  - Electrical and chemical synapses among parvalbumin fast-spiking GABAergic
      interneurons in adult mouse neocortex.
AB  - Networks of gamma-aminobutyric acid (GABA)ergic interneurons connected via
      electrical and chemical synapses are thought to play an important role in
      detecting and promoting synchronous activity in the cerebral cortex. Although the
      properties of electrical and chemical synaptic interactions among inhibitory
      interneurons are critical for their function as a network, they have only been
      studied systematically in juvenile animals. Here, we have used transgenic mice
      expressing the enhanced green fluorescent protein in cells containing parvalbumin
      (PV) to study the synaptic connectivity among fast-spiking (FS) cells in slices
      from adult animals (2-7 months old). We have recorded from pairs of PV-FS cells
      and found that the majority of them were electrically coupled (61%, 14 of 23
      pairs). In addition, 78% of the pairs were connected via GABAergic chemical
      synapses, often reciprocally. The average coupling coefficient for step
      injections was 1.5% (n = 14), a smaller value than that reported in juvenile
      animals. GABA-mediated inhibitory postsynaptic currents and potentials decayed
      with exponential time constants of 2.6 and 5.9 ms, respectively, and exhibited
      paired-pulse depression (50-ms interval). The inhibitory synaptic responses in
      the adult were faster than those observed in young animals. Our results indicate
      that PV-FS cells are highly interconnected in the adult cerebral cortex by both
      electrical and chemical synapses, establishing networks that can have important
      implications for coordinating activity in cortical circuits.

PMID- 12213964
TI  - The structural basis for the transition from Ras-GTP to Ras-GDP.
AB  - The conformational changes in Ras that accompany the hydrolysis of GTP are
      critical to its function as a molecular switch in signaling pathways.
      Understanding how GTP is hydrolyzed by revealing the sequence of intermediary
      structures in the reaction is essential for understanding Ras signaling. Until
      now, no structure of an intermediate in GTP hydrolysis has been experimentally
      determined for Ras alone. We have solved the crystal structure of the Ala-59 to
      Gly mutant of Ras, (RasA59G), bound to guanosine 5'-imidotriphosphate or GDP to
      1.7-A resolution. In the guanosine 5'-imidotriphosphate-bound form, this mutant
      adopts a conformation that is intermediate between the GTP- and GDP-bound forms
      of wild-type Ras and that is similar to what has been predicted by molecular
      dynamics simulation [Ma, J. P. & Karplus, M. (1997) Proc. Natl. Acad. Sci. USA
      94, 11905-11910]. This conformation is stabilized by direct and water-mediated
      interactions between the switch 1 and switch 2 regions and is characterized by an
      increase in the binding affinity for GTP. We propose that the structural changes
      promoted by the Ala-59 to Gly mutation exhibit a discrete conformational state
      assumed by wild-type Ras during GTP hydrolysis.

PMID- 12213963
TI  - Identifying novel transcripts and novel genes in the human genome by using novel
      SAGE tags.
AB  - The number of genes in the human genome is still a controversial issue. Whereas
      most of the genes in the human genome are said to have been physically or
      computationally identified, many short cDNA sequences identified as tags by use
      of serial analysis of gene expression (SAGE) do not match these genes. By
      performing experimental verification of more than 1,000 SAGE tags and analyzing
      4,285,923 SAGE tags of human origin in the current SAGE database, we examined the
      nature of the unmatched SAGE tags. Our study shows that most of the unmatched
      SAGE tags are truly novel SAGE tags that originated from novel transcripts not
      yet identified in the human genome, including alternatively spliced transcripts
      from known genes and potential novel genes. Our study indicates that by using
      novel SAGE tags as probes, we should be able to identify efficiently many novel
      transcripts/novel genes in the human genome that are difficult to identify by
      conventional methods.

PMID- 12213965
TI  - Protein assembly and heat stability in developing thylakoid membranes during
      greening.
AB  - The development of the thylakoid membrane was studied during illumination of dark
      grown barley seedlings by using biochemical methods, and Fourier transform
      infrared and spin label electron paramagnetic resonance spectroscopic techniques.
      Correlated, gross changes in the secondary structure of membrane proteins,
      conformation, composition, and dynamics of lipid acyl chains, SDS/PAGE pattern,
      and thermally induced structural alterations show that greening is accompanied
      with the reorganization of membrane protein assemblies and the protein-lipid
      interface. Changes in overall membrane fluidity and noncovalent protein-lipid
      interactions are not monotonic, despite the monotonic accumulation of
      chlorophyll, LHCII [light-harvesting chlorophyll a/b-binding (polypeptides)
      associated with photosystem II] apoproteins, and 18:3 fatty acids that follow a
      similar time course with highest rates between 12-24 h of greening. The 18:3
      fatty acid content increases 2.8-fold during greening. This appears to both
      compensate for lipid immobilization by membrane proteins and facilitate packing
      of larger protein assemblies. The increase in the amount of protein-solvating
      immobile lipids, which reaches a maximum at 12 h, is caused by 40% decrease in
      the membranous mean diameter of protein assemblies at constant protein/lipid mass
      ratio. Alterations in the SDS/PAGE pattern are most significant between 6-24 h.
      The size of membrane protein assemblies increases approximately 4.5-fold over the
      12-48-h period, likely caused by the 2-fold gain in LHCII apoproteins. The
      thermal stability of thylakoid membrane proteins increases monotonically, as
      detected by an increasing temperature of partial protein unfolding during
      greening. Our data suggest that a structural coupling between major protein and
      lipid components develops during greening. This protein-lipid interaction is
      required for the development and protection of thylakoid membrane protein
      assemblies.

PMID- 12213966
TI  - Molecular mechanisms of cardiac hypertrophy induced by toxicants.
AB  - Cardiac hypertrophy is an end point of chronic cardiac toxicity from a number of
      toxicants. Doxorubicin, cocaine, acetaldehyde, monocrotaline, and azide are
      examples of these toxicants, which may induce hypertrophy by increasing oxidants,
      circulating levels of catecholamines, and hemodynamic load or by inducing
      hypoxia. We summarize here the major signal transduction pathways and common
      changes in gene expression found with the classical hypertrophy inducers
      angiotensin II, endothelin 1, and catecholamines. Activation of G-proteins,
      calcium signaling, phosphoinositide 3-kinase (PI3K), certain family members of
      protein kinase Cs (PKCs), and three branches of mitogenactivated protein kinases
      (MAPKs), i.e. extracellular signal-regulated kinases (ERKs), p38, and c-Jun N
      terminal kinases (JNKs), are important for developing a hypertrophic phenotype in
      cardiomyocytes. Characteristic changes of gene expression in hypertrophy include
      the elevated transcription of atrial natriuretic factor (ANF), beta-myosin heavy
      chain (beta MHC), skeletal alpha-actin (SkA), certain variants of integrins and
      perhaps tubulin genes, and reduced expression of the sarcoplasmic reticulum
      proteins phospholamban and sarco(endo)plasmic reticulum Ca2+-ATPase 2 alpha
      (SERCA2 alpha), and of the ryanodine receptors. Although which toxicants induce
      these molecular changes remains to be tested, increasing lines of evidence
      support that oxidants play a central role in cardiac hypertrophy. Oxidants
      activate small G-proteins, calcium signaling, PI3K, PKCs, and MAPKs. Oxidants
      cause cardiomyocytes to enlarge in vitro. Recent developments in transgenic,
      genomic, and proteomic technologies will provide needed tools to reveal the
      mechanism of chronic cardiac toxicity at the cellular and molecular levels.

PMID- 12213967
TI  - Dioxin exposure is an environmental risk factor for ischemic heart disease.
AB  - Epidemiologic studies have linked dioxin exposure to increased mortality caused
      by ischemic heart disease. To test the hypothesis that dioxin exposure may
      constitute an environmental risk factor for atherosclerosis, we exposed C57BL/6J
      mice to 5 microg/kg of dioxin daily for 3 d, and measured various molecular and
      physiological markers of heart disease. Dioxin treatment led to an increase in
      the urinary excretion of vasoactive eicosanoids and an elevation in the mean tail
      cuff blood pressure. In addition, dioxin exposure led to an increase in
      triglycerides, but not in high-density lipoproteins, in both Apoe(+/+) mice and
      in hyperlipidemic Apoe(-/- mice. Dioxin exposure also led to an increase in low
      density lipoproteins in Apoe(-/-) mice. After treatment, dioxin was associated
      with low-density lipoprotein particles, which might serve as a vehicle to deliver
      the compound to atherosclerotic plaques. Dioxin treatment of vascular smooth
      muscle cells taken from C57Bl/6J mice resulted in the deregulation of several
      genes involved in cell proliferation and apoptosis. Subchronic treatment of Apoe(
      /-) mice with dioxin (150 ng/kg, three times weekly) for 7 or 26 wk caused a
      trend toward earlier onset and greater severity of atherosclerotic lesions
      compared to those of vehicle treated mice. These results suggest that dioxin may
      increase the incidence of ischemic heart disease by exacerbating its severity.

PMID- 12213968
TI  - The effects of cardiac myocytes on interstitial fibroblasts in toxic iron
      overload.
AB  - Iron deposits preferentially in myocytes in mixed cultures of cardiac myocytes
      and nonmyocytic fibroblasts. In vivo, iron overload is associated with cardiac
      fibrosis. Therefore, we examined whether iron loading of cardiac myocytes in
      culture could trigger a response in nonmyocytes characteristic of a fibrogenic
      phenotype. We found that the nonmyocytes adopted a myofibroblast phenotype in
      culture. The rate of DNA synthesis (measured by [3H]thymidine incorporation) by
      the nonmyocytes was decreased by the myocyte-conditioned medium, compared to that
      of the unconditioned medium, and this activity was retained in <10-kDa fractions.
      The rate was partially restored when the medium was obtained from iron-loaded
      myocytes, and in this medium, the <10-kDa fraction was even more effective in
      reversing the suppression of proliferation. This suppression suggests a decreased
      secretion of a growth inhibitory substance in the iron-loaded myocytes, and this
      effect was partially reversed when the iron-loaded cells were treated with the
      iron chelator, deferoxamine. This indicates that cardiac myocytes may play a
      paracrine role in suppressing the proliferation of myofibroblasts that is
      partially overcome when the myocytes are iron overloaded. The myocyte-conditioned
      medium also affects the myofibroblast phenotype, increasing the cells'
      fibronectin mRNA content and decreasing alpha-smooth-muscle actin mRNA. The
      myocyte-conditioned medium increases transforming growth factor-beta (TGF-beta)
      secretion by myofibroblasts, but the TGF-beta content of the conditioned medium
      was found to play, at most, a minor role in determining the response of the
      myofibroblast.

PMID- 12213969
TI  - Oxidant-induced inhibition of myocardial calcium-independent phospholipase A2.
AB  - We discovered the acute inhibition of myocardial phospholipase A2 activity by
      micromolar concentrations of tert-butyl hydroperoxide and hydrogen peroxide.
      Specifically, freshly isolated adult rat cardiomyocytes were treated with the
      oxidants for 30 min, and phospholipase A2 activity was assessed in cell
      subcellular fractions using (16:0, [3H]18:1) plasmenylcholine and
      phosphatidylcholine substrates in the absence or presence of calcium. Calcium
      independent phospholipase A2 activity was inhibited by approx 50% in both the
      cytosolic and membrane fractions by the oxidants. The inhibition of the
      phospholipase A2 activity was concentration dependent and preceded detectable
      changes in cell viability as assessed by lactate dehydrogenase release and rod
      shaped morphology. Taking into account that oxidized sn-2 fatty acyl groups must
      first be hydrolyzed by phospholipase A2 to be repaired by glutathione peroxidase,
      we suggest that the observed inhibition of phospholipase A2 activity by oxidants
      compromises the myocyte's ability to deal with lipid peroxidation. This
      conclusion was further validated by the experiments in which pretreatment with
      the calcium-independent phospholipase A2 inhibitor bromoenol lactone exacerbated
      cardiotoxicity of tert-butyl hydroperoxide in myocyte cultures.

PMID- 12213971
TI  - Oxidative stress and diabetic cardiomyopathy: a brief review.
AB  - Diabetes is a serious public health problem. Improvements in the treatment of
      noncardiac complications from diabetes have resulted in heart disease becoming a
      leading cause of death in diabetic patients. Several cardiovascular pathological
      consequences of diabetes such as hypertension affect the heart to varying
      degrees. However, hyperglycemia, as an independent risk factor, directly causes
      cardiac damage and leads to diabetic cardiomyopathy. Diabetic cardiomyopathy can
      occur independent of vascular disease, although the mechanisms are largely
      unknown. Previous studies have paid little attention to the direct effects of
      hyperglycemia on cardiac myocytes, and most studies, especially in vitro, have
      mainly focused on the molecular mechanisms underlying pathogenic alterations in
      vascular smooth-muscle cells and endothelial cells. Thus, a comprehensive
      understanding of the mechanisms of diabetic cardiomyopathy is urgently needed to
      develop approaches for the prevention and treatment of diabetic cardiac
      complications. This review provides a survey of current understanding of diabetic
      cardiomyopathy. Current consensus is that hyperglycemia results in the production
      of reactive oxygen and nitrogen species, which leads to oxidative myocardial
      injury. Alterations in myocardial structure and function occur in the late stage
      of diabetes. These chronic alterations are believed to result from acute cardiac
      responses to suddenly increased glucose levels at the early stage of diabetes.
      Oxidative stress, induced by reactive oxygen and nitrogen species derived from
      hyperglycemia, causes abnormal gene expression, altered signal transduction, and
      the activation of pathways leading to programmed myocardial cell deaths. The
      resulting myocardial cell loss thus plays a critical role in the development of
      diabetic cardiomyopathy. Advances in the application of various strategies for
      targeting the prevention of hyperglycemia-induced oxidative myocardial injury may
      be fruitful.

PMID- 12213972
TI  - Copper enhances isoproterenol toxicity in isolated rat cardiomyocytes: effects on
      oxidative stress.
AB  - Sustained high levels of circulating catecholamines may result in cardiotoxicity.
      Although cardiotoxicity could occur primarily via adrenoceptor activation, there
      is increasing evidence that it may also occur through oxidative mechanisms. In
      fact, catecholamines can be converted into aminochromes by auto-oxidation,
      enzymatically or metal catalyzed, with the concomitant production of reactive
      intermediates and free radicals. Nevertheless, there is only scarce information
      concerning the effects of the catecholamine oxidation process on isolated
      cardiomyocytes. The aim of this work was to evaluate the cardiotoxic effects of
      isoproterenol (ISO) and its oxidation process in freshly isolated adult rat
      cardiomyocytes by assessing the cell shape, lactate dehydrogenase leakage,
      reduced and oxidized glutathione content, and glutathione reductase, peroxidase,
      and transferase activities. ISO was incubated at concentrations of 0.1, 0.5, and
      1 mM in cardiomyocyte suspensions at subphysiological and physiological Ca2+
      concentrations for 4 h. The same study was repeated in the presence of 20 microM
      of Cu2+. The levels of ISO in the incubation medium were monitored throughout the
      assays. Isoproterenol (1 mM) induced both glutathione oxidation and conjugation,
      but this effect decreased at subphysiological Ca2+ concentrations. The
      concomitant incubation with Cu2+ increased ISO oxidation and increased the
      glutathione oxidation but decreased the extent of glutathione conjugation.
      Although only a partial ISO oxidation was observed for all studied ISO
      concentrations in the presence of copper, the underlying oxidative process or its
      oxidation products, or both, were sufficient to induce a loss of cardiomyocyte
      viability and a decrease in the glutathione reductase, peroxidase, and
      transferase activities. Thus, the results suggest that the oxidation of
      catecholamines could be a major mechanism for catecholamine-induced
      cardiotoxicity.

PMID- 12213973
TI  - Carvedilol reduces mitochondrial damage induced by hypoxanthine/xanthine oxidase:
      relevance to hypoxia/reoxygenation injury.
AB  - The cardioprotective properties of new pharmaceuticals such as carvedilol might
      be explained by enhanced mitochondrial protection. The aim of this work was to
      determine the role of carvedilol in the protection of heart mitochondria from
      oxidative damage induced by hypoxanthine/xanthine oxidase, a known source of
      oxidative stress in the vascular system. Carvedilol reduced oxidative-stress
      induced mitochondrial injury, as seen by the delay in the loss of the
      mitochondrial transmembranar potential (Delta Psi), the decrease in mitochondrial
      swelling, and the increase in mitochondrial calcium uptake. Carvedilol improved
      the mitochondrial respiratory activity in state III and offered an overall
      protection in the respiratory control and in the P/O ratios in mitochondria under
      oxidative stress. The data indicated that carvedilol was able to partly protect
      heart mitochondria from oxidative stress-induced damage. Our results suggest that
      mitochondria can be important targets for some cardioprotective pharmaceuticals.

PMID- 12213974
TI  - Prenatal ethanol exposure alters ventricular myocyte contractile function in the
      offspring of rats: influence of maternal Mg2+ supplementation.
AB  - Fetal alcohol syndrome (FAS) is often associated with cardiac hypertrophy and
      impaired ventricular function in a manner similar to postnatal chronic alcohol
      ingestion. Chronic alcoholism has been shown to lead to hypomagnesemia, and
      dietary Mg2+ supplementation was shown to ameliorate ethanol- induced
      cardiovascular dysfunction such as hypertension. However, the role of gestational
      Mg2+ supplementation on FAS-related cardiac dysfunction is unknown. This study
      was conducted to examine the influence of gestational dietary Mg2+
      supplementation on prenatal ethanol exposure-induced cardiac contractile response
      at the ventricular myocyte level. Timed-pregnancy female rats were fed from
      gestation day 2 with liquid diets containing 0.13 g/L Mg2+ supplemented with
      ethanol (36%) or additional Mg2+ (0.52 g/L), or both. The pups were maintained on
      standard rat chow through adulthood, and ventricular myocytes were isolated and
      stimulated to contract at 0.5 Hz. Mechanical properties were evaluated using an
      IonOptix soft-edge system, and intracellular Ca2+ transients were measured as
      changes in fura-2 fluorescence intensity (Delta FFI). Offspring from all groups
      displayed similar growth curves. Myocytes from the ethanol group exhibited
      reduced cell length, enhanced peak shortening (PS), and shortened time to 90%
      relengthening (TR90) associated with a normal Delta FFI and time to PS (TPS).
      Mg2+ reverted the prenatal ethanol-induced alteration in PS and maximal velocity
      of relengthening. However, it shortened TPS and TR90, and altered the Delta FFI,
      as well as Ca2+ decay rate by itself. Additionally, myocytes from the ethanol
      group exhibited impaired responsiveness to increased extracellular Ca2+ or
      stimulating frequency, which were restored by gestational Mg2+ supplementation.
      These data suggest that although gestational Mg2+ supplementation may be
      beneficial to certain cardiac contractile dysfunctions in offspring of alcoholic
      mothers, caution must be taken, as Mg2+ supplementation affects cell mechanics
      itself.

PMID- 12213975
TI  - Expression of HoxA5 in the heart is upregulated during thyroxin-induced
      metamorphosis of the Mexican axolotl (Ambystoma mexicanum).
AB  - Widespread external and internal changes in body morphology have long been known
      to be hallmarks of the process of metamorphosis. However, more subtle changes,
      particularly at the molecular level, are only now beginning to be understood. A
      number of transcription factors have recently been shown to alter expression
      either in levels of message or in isoforms expressed. In this article, we
      describe a dramatic increase in the expression of the homeobox gene HoxA5 in the
      heart and aorta of the Mexican axolotl Ambystoma mexicanum during the process of
      thyroxin-induced metamorphosis. Immunohistochemical analysis with anti-HoxA5
      antibody in thyroxin-induced metamorphosing animals showed a pattern of
      expression of HoxA5 comparable to that in spontaneously metamorphosing animals.
      Further, by in situ hybridization, we were able to show significant qualitative
      differences in the expression of this gene within the heart. Maximum HoxA5
      expression occurred at the midpoint of metamorphosis in the myocardium, whereas
      the hearts of completely metamorphosed animals had the highest levels of
      expression in the epicardium and endocardium. In the aorta, smooth-muscle cells
      of the tunica media as well as cells of the tunica adventitia had an increase in
      expression of HoxA5 with thyroxin-induced metamorphosis. HoxA5 expression
      significantly changed in cells of the aorta and ventricle with treatment by
      thyroid hormone. HoxA5, a positive regulator of p53, may be involved with the
      apoptotic pathway in heart remodeling during amphibian metamorphosis.

PMID- 12213976
TI  - Lovastatin inhibits phenylephrine-induced ERK activation and growth of cardiac.
AB  - The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) exert
      numerous cellular effects through the inhibition of cholesterol synthesis. The
      objectives of these experiments were to determine the following: (1) whether
      lovastatin (LOV) inhibits phenylephrine (PE)-induced growth of neonatal rat
      cardiac myocytes without inducing cytotoxicity and (2) whether growth-inhibiting
      effects of LOV are associated with reduced PE activation of extracellular signal
      regulated kinases 1 and 2 (ERK 1/2). After 48 h of exposure, LOV alone (0.1-10
      microM) inhibited 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide
      (MTT) reduction without significant changes in propidium iodide staining, and 100
      microM mevalonic acid prevented the effect of LOV on MTT reduction. PE (50 or 100
      microM for 48 h) induced significant increases in protein-to-DNA ratios. PE (100
      microM for 5 min) significantly increased the phosphorylated forms of ERK 1 and
      ERK 2 and activity of ERK. After 24 h pretreatment or 48 h cotreatment, LOV (10
      microM) significantly inhibited PE-induced growth. In addition, LOV pretreatment
      significantly inhibited the stimulatory effect of PE on ERK 2 phosphorylation and
      ERK activity. These results demonstrate that LOV, at concentrations that do not
      alter membrane integrity, inhibits PE-induced growth of cardiac myocytes,
      potentially through reduced activation of ERK 1/2.

PMID- 12213977
TI  - Early evolution from ischemia to myocardial necrosis.
AB  - The presence, age, and extent of myocardial ischemic injury can be determined
      with some precision using pathologic techniques. Electron microscopic studies can
      detect very early ischemic injury, only minutes old, even before irreversible
      injury (i.e., necrosis) is present; however, because of the small amount of
      tissue sampled, ultrastructural studies are not very useful for quantifying the
      size of the ischemic zone. Histologic studies can detect irreversible injury only
      hours old, and because large samples can be studied, the necrotic zone can be
      measured quite efficiently. In addition, the age of the infarct can be
      determined. The knowledge gleaned from such morphologic studies continues to
      contribute to the development of new diagnostic tests and therapies for patients
      with ischemic heart disease.

PMID- 12213978
TI  - Elevations in cardiac troponin measurements: false false-positives: the real
      truth.
AB  - The development of assays for troponin markers has improved cardiovascular
      diagnosis. However, because the assays are so sensitive and specific, elevations
      are often detected in patients without overt coronary artery disease. Some would
      like to attribute such elevations to biological "false positives." That is rarely
      the case. There can be analytic false positives but most such elevations are
      indicative of subtle degrees of cardiac injury, many not related to ischemic
      heart disease. The spectrum of such increases and their potential etiologies are
      elaborated in this article.

PMID- 12213979
TI  - Cardiac troponin assays: analytical issues and clinical reference range
      cutpoints.
AB  - A recently published consensus document from the European Society of Cardiology
      and American College of Cardiology emphasized the unique role cardiac troponin
      monitoring plays in redefining acute myocardial infarction. The cardiology
      community has now established criteria to define both the reference cutpoints and
      acceptable imprecision for troponin assays, which complement previous
      recommendations by the laboratory community. This article will review the
      analytical issues confronting laboratories, clinicians, and industry regarding
      troponin assay standardization, assay imprecision, and how clinical decision
      cutpoints should be established and implemented for clinical practice.

PMID- 12213980
TI  - Cardiac troponin T in ST-segment elevation acute myocardial infarction revisited.
AB  - Cardiac troponins not only allow for risk stratification and guidance of therapy
      in unstable angina and non-Q-wave acute myocardial infarction but also may be
      useful in the diagnostic workup and monitoring of patients with ST-segment
      elevation myocardial infarction. In clinical practice, troponins are used for
      confirmation and monitoring of myocardial infarction, noninvasive prediction of
      reperfusion success after thrombolytic therapy, and noninvasive estimation of
      infarct size. Accumulating evidence suggests that the measurement of cardiac
      troponins on admission may represent a relatively novel application that is
      useful for early risk stratification and prediction of reperfusion success after
      thrombolysis or primary percutaneous coronary interventions. Potential mechanisms
      of the predictive power of cardiac troponins are discussed.

PMID- 12213981
TI  - Troponins in patients with acute coronary syndromes: biologic, diagnostic, and
      therapeutic implications.
AB  - The cardiac troponins have expanded the spectrum of detectable myocardial injury
      and enhanced the clinician's ability to identify patients with acute coronary
      syndromes who are at higher risk for death or recurrent ischemic events. Based on
      available data, it appears most likely that any reliably detected troponin
      elevation results from myocyte necrosis. This notion has served as the basis for
      the recent revision of diagnostic criteria for acute myocardial infarction based
      on cardiac troponin. Nevertheless, further research is necessary to conclusively
      refute the possibility that the release of cardiac troponins may also occur in
      the setting of reversible myocyte injury resulting from cellular ischemia. Such
      an investigation establishing biologic correlates of troponin elevation is likely
      to prove valuable in guiding diagnostic terminology as well as in therapy. For
      example, clinical research finding cardiac troponin elevation to be predictive of
      intracoronary thrombus and distal microvascular obstruction has been important to
      the evaluation of troponins for targeting powerful antiplatelet and antithrombin
      therapies. Whether related to irreversible or reversible injury, the cardiac
      troponins have blurred the traditional boundaries between unstable angina and
      myocardial infarction and have evolved as powerful tools for risk stratification
      and therapeutic decision-making.

PMID- 12213982
TI  - Markers and the initial triage and treatment of patients with chest pain.
AB  - Emergency departments evaluate nearly 8 million patients with chest pain per
      year. Nearly 4 million of these individuals are admitted to inpatient units for
      further evaluation and treatment, but only 30% of these admitted patients
      ultimately have the diagnosis of acute coronary syndrome (ACS). Previously, the
      initial evaluation of patients with chest discomfort presenting to the emergency
      department (ED) involved the triad of history, physical, and ECG. Current
      evidence demonstrates that a fourth element, cardiac markers, serves as a
      valuable aid in not only determining initial diagnosis but also providing risk
      stratification and dictating initial patient treatment. Chest pain units (CPUs)
      using serial marker determinations have been successful in identifying patients
      with or at risk for adverse cardiac events in a timely and cost- efficient
      manner. New point-of-care-testing (POCT) of cardiac markers at the patient's
      bedside allows for even more timely determination. This article will review the
      use of cardiac markers in heterogeneous patients presenting to EDs with chest
      discomfort. We will focus on the use of markers in the risk stratification and
      initial treatment of the ED chest pain population and emphasize the role of CPUs
      and POCT.

PMID- 12213983
TI  - Improved identification of acute coronary syndromes with delta cardiac serum
      marker measurements during the emergency department evaluation of chest pain
      patients.
AB  - Current findings from the American College of Emergency Physicians (ACEP) are
      that no serum marker reliably identifies or excludes acute myocardial infarction
      (AMI) within 6 h of symptom onset. The ACEP recommends repeat serum marker
      testing 6-10 h after symptom onset for CK-MB mass and subform, and 8-12 h after
      symptom onset for cardiac troponin I and T before making an exclusionary
      diagnosis of non-AMI chest pain. A new approach for identifying myocardial
      necrosis is to rely on time changes in the serum marker value over an abbreviated
      time interval (slope or delta values) as opposed to the traditional approach of
      relying on a value exceeding the threshold of normalcy. As assays become ever
      more sensitive and precise, this approach has the potential for both reliably
      identifying and excluding AMI (and subsets of high-risk unstable angina) at
      earlier time intervals with no loss in specificity. This article discusses some
      of the experimental evidence for this delta approach and some preliminary
      evidence for the potential of utilizing second-generation cTnI assays for the
      identification of acute coronary syndromes. Finally, we discuss a unique way of
      viewing receiver-operating characteristic (ROC) curves as catalogs of likelihood
      ratios, which we believe will be more useful to the clinician in the proper
      interpretation of serum marker values.

PMID- 12213984
TI  - Rationale for the early clinical application of markers of ischemia in patients
      with suspected acute coronary syndromes.
AB  - Mandates for more rapid treatment of patients with acute myocardial infarction
      (AMI) are driving public education initiatives aimed at having patients present
      earlier in the course of their symptoms. This will make it less likely that
      markers of necrosis will provide the level of diagnostic sensitivity needed. In
      fact, the goal is to identify and treat these patients sooner in order to prevent
      necrosis from occurring. Given the limitations of the standard 12-lead ECG to
      detect ischemia, other technologies are being evaluated: the value of
      echocardiography and technetium-based myocardial perfusion imaging have been
      proven. However, the goal is to develop a simple, rapid-turn-around biochemical
      marker that can provide this same function, and clear progress is being made
      toward this end. Emergent, rapid restoration of blood flow via pharmacologic
      revascularization or primary percutaneous interventions can reduce morbidity and
      mortality when applied in the setting of acute myocardial injury seen on the ECG.
      Exciting new research suggests that the protection of myocytes against ischemic
      injury is possible if initiated early, which can limit cellular damage and
      improve clinical outcomes. Thus, the ability to rapidly detect ischemia will have
      profound therapeutic possibilities that could further reduce the morbidity and
      mortality associated with acute coronary syndrome.

PMID- 12213985
TI  - Clinical and pathobiologic considerations in the evaluation of markers of
      myocardial ischemia.
AB  - There is a need for blood-based analytic techniques that allow for the detection
      of patients either with reversible myocardial ischemia or who are at risk for
      myocardial ischemia. However, given the diverse etiologies of unstable angina and
      the complex interactions among various cell types, the term "marker for ischemia"
      should be used with caution (if at all). Unless we find a protein that is
      released across the diverse pathologic triggers associated with the various
      stages of progression of atherosclerosis and cellular ischemia, we will be forced
      to consider a spectrum of proteins (and analytic assays) that are situationally
      specific. The choice of an appropriate gold standard as we investigate the
      clinical application of these assays will be one of the most difficult and most
      important decisions in these studies. It will be critical that conclusions of
      usefulness in one setting of ischemic heart disease not be generalized in the
      absence of clinical trials supporting that contention.

PMID- 12213986
TI  - Markers of platelet activation and thrombin generation.
AB  - The laboratory assessment of platelet biology and coagulation has traditionally
      focused on abnormalities, congenital or acquired, that provide insights for
      understanding hemostatic defects, unexplained bleeding, and pharmacologic
      titration of compounds designed to attenuate thrombotic potential. Because
      atherosclerotic vascular disease is associated with thrombotic events and there
      exists a clear link between atherosclerosis, inflammation, and thrombosis, the
      development of markers that have pathobiologic, prognostic, and treatment-
      related relevance has taken on a role of considerable importance.

PMID- 12213987
TI  - Analysis of the Albumin Cobalt Binding (ACB) test as an adjunct to cardiac
      troponin I for the early detection of acute myocardial infarction.
AB  - Human albumin has the ability to bind cobalt at the N-terminus. The exposure of
      circulating albumin to ischemic tissue alters the ability of albumin to bind
      cobalt, probably through a mechanism involving free-radical production. The
      Albumin Cobalt Binding (ACB) test measures the alteration in albumin metal
      binding, and elevation of the ACB test is thought to be an early indicator of
      myocardial ischemia. In a previous multicenter study of chest pain patients
      presenting to the emergency department (ED), this test demonstrated high negative
      predictive value and sensitivity in the sample collected at presentation for
      predicting cardiac troponin I (cTnI)-negative or cTnI-positive results 6-24 h
      later. Since the completion of that report, the European Society of Cardiology
      (ESC) and the American College of Cardiology (ACC) have redefined the criteria
      for the diagnosis of acute myocardial infarction (AMI). The data from the
      multicenter ACB study were re-examined using the new diagnostic criteria for AMI
      to determine if combining the ACB test with troponin improved the sensitivity of
      either assay used alone for early diagnosis of AMI. Assay values were compared to
      either the final discharge diagnosis made at each site or to a diagnosis of AMI
      using the strict application of the ESC/ACC guidelines. Using the criterion of
      physician's discharge diagnosis and using blood collected at ED presentation, the
      cTnI test alone had a sensitivity of 23.9%, and the ACB test alone had a
      sensitivity of 39.1%, but the sensitivity significantly increased to 55.9% (p <
      0.001 over cTnI alone) when both tests were used in combination. The sensitivity
      of the combination of ACB and cTnI tests at the 1- to 6-h time-point was 86.7%
      and at the >6- to 12-h time-point was 93.5%, but they were not significantly
      improved over the cTnI test alone. In conclusion, using the new ESC/ACC criteria,
      the combination also resulted in a statistically significant higher diagnostic
      sensitivity on blood collected at presentation. These data indicate a possible
      role of the ACB test in the early triage of patients with chest pain.

PMID- 12213988
TI  - C-reactive protein and coronary heart disease: diagnostic and therapeutic
      implications for primary prevention.
AB  - Coronary heart disease (CHD) is the leading cause of death in the industrialized
      world. Recent laboratory and clinical studies have shown that inflammation plays
      a pivotal role in the inception, progression, and destabilization of atheromas.
      The acute-phase reactant C-reactive protein (CRP) has been shown to reflect
      systemic and, perhaps, vascular inflammation and to predict future cardiovascular
      events in asymptomatic individuals. The relative risk associated with CRP is
      independent of other cardiovascular disease risk factors. High-sensitivity assays
      (hs-CRP) are needed for the measurement of CRP concentration for the purpose of
      predicting the risk of future coronary events. Available assays must be
      standardized because patients' results will be interpreted using population-based
      cutpoints. An algorithm for risk stratification incorporating hs-CRP and total
      cholesterol to high-density lipoprotein cholesterol ratio has been developed.
      Statin class drugs and aspirin appear to modulate CHD risk in those with
      increased hs-CRP concentration. Several prospective studies are now underway to
      specifically develop novel clinical utilities and therapeutic strategies for hs
      CRP.

PMID- 12213989
TI  - B-type natriuretic peptide levels: diagnostic and therapeutic potential.
AB  - A blood test that would aid in the diagnosis and management of patients with
      congestive heart failure would have a favorable impact on the staggering costs of
      the disease. B-type naturetic peptide (BNP) is synthesized in the cardiac
      ventricles and its release is directly proportional to ventricular volume
      expansion and pressure overload. Levels of BNP correlate with left ventricular
      pressure, amount of dyspnea, and the state of neurohumoral modulation. BNP also
      correlates closely with New York Heart Association classification. A cut point of
      100 pg/mL appears to discriminate patients with congestive heart failure from
      those without congestive heart failure. Measurement of BNP may also be an
      excellent screening tool for LV dysfunction. Key Words: Natriuretic peptides;
      neurohormonal; left-ventricular pressure;

PMID- 12213990
TI  - Mammalian cardenolides as biomarkers in congestive heart failure.
AB  - Congestive heart failure (CHF) afflicts over 5 million individuals in the United
      States, and most die within 5 yr of diagnosis. Because of the high morbidity and
      mortality associated with CHF, the search for biomarkers to predict, diagnose,
      and manage this disease has intensified. Calcium homeostasis and alterations in
      intracellular concentrations of this cation have been implicated in both
      hypertrophy as well as the adaptive mechanisms observed in CHF. In this article,
      we discuss the roles of the sodium pump and the endogenous mammalian cardenolides
      and their involvement in the pathophysiology of this disease in view of the
      regulation of intracellular calcium. Understanding the mechanisms for the release
      of mammalian cardenolides in plasma, the alterations in sodium pump isoforms and
      function, and the modulation of pathways involving calcium in hypertrophy and CHF
      may assist in the development of new biological markers capable of predicting the
      disease before significant progression and irreversible heart failure.

PMID- 12213991
TI  - Determination of the falloff constant (k(f)) from modeling biochemical marker
      release: a new variable for discriminating therapies.
AB  - A new variable termed the falloff constant (k(f)) was derived from the curve
      fitting of serial CK-MB measurements. k(f) represents the rate constant of
      maximal decline in serum CK-MB and is determined from the slope of the lognormal
      curve at the inflection point. Physiologically, kf's magnitude reflects the
      balance between CK-MB's rate of release from tissue and the rate of elimination.
      We examined k(f) in two myocardial infarction (MI) patient sets. The first set
      was homogeneous and taken from the TAMI 7 study (n = 147) and included 111
      patients having TIMI 2-3 flow after thrombolytic therapy and 36 patients who
      initially had TIMI 0-1 flow. The TIMI 0-1 patients were opened to TIMI 3 by
      angioplasty within 3 h. The second set consisted of 196 patients enrolled in the
      IMPACT-AMI study that demonstrated the efficacy of the glycoprotein (GP) IIb/IIIa
      antagonist eptifibatide. This second set consisted of 93 patients in the GP
      IIb/IIIa treatment group and 103 in the placebo group. Log-normal curve-fitting
      parameters including peak maximum and curve area were also compared to k(f) in
      the GP IIb/IIIa versus placebo set. The Wilcoxon test showed no difference
      between the two groups of TAMI 7 patients (p = 0.22). However, there was a highly
      significant difference in kf between the GP IIb/IIIa treatment group versus the
      placebo group (p = 0.0014). Both k(f) and peak maximum from curve fitting showed
      significant differences between the GP IIb/IIIa treatment group and the placebo
      group; however, k(f) showed a substantially lower p-value (p = 0.0014 and p =
      0.023, respectively). As expected, k(f) showed no difference between the TAMI 7
      groups because this was a homogeneous patient set in that they all had TIMI 3
      patency status within 3 h of treatment. However, in the patient set having very
      different treatments, GP IIb/IIIa versus placebo, there was a highly significant
      difference in the kf variable. These data suggest that differences in reperfusion
      are reflected by kf and that this variable may represent a valuable new
      nonmortality end point derived from curve fitting analysis.

PMID- 12213992
TI  - Gene therapy and molecular toxicology: a commentary.

PMID- 12213993
TI  - Metabonomic assessment of vasculitis in rats.
AB  - The vasculitides are a heterogeneous group of lesions characterized by
      inflammation and necrosis of the vascular wall and have proven to be a
      disconcerting dilemma in the development of several classes of therapeutics.
      Metabonomics is an emerging technology having great potential for rapid
      noninvasive assessment of toxicity in vivo and providing identification of
      peripheral surrogate markers of toxicity. Metabonomic evaluation of CI-1018, a
      selective type 4 phosphodiesterase inhibitor associated with vasculitis in rats,
      was undertaken. Two experiments were performed in which CI-1018 was administered
      for up to 4 d to groups of male Wistar rats at doses up to 3000 mg/kg. Urine was
      collected from all animals pretest and daily for metabonomic analysis. Eleven of
      38 CI-1018-treated animals were found to have vascular injury of varying severity
      at doses = or > 750 mg/kg. Principal component analysis produced a clear pattern
      separation among 8 of 11 animals with lesions and 36 of 37 animals without
      lesions in samples collected on d 3 or 4. These data demonstrate that the
      metabonomics approach has significant potential for developing a noninvasive
      method for identifying vasculitis in rats. It remains to be seen if urinary
      analyte patterns identified in this study are reproducible and whether a
      biomarker pattern for vasculitis can be established.

PMID- 12213994
TI  - Is cytotoxic cellular edema real? The effect of calcium ion on water homeostasis
      in the rat heart.
AB  - The objective of this study was to determine the effect of calcium on water
      homeostasis in cardiac muscle and whether cytotoxic edema is involved in ischemic
      reperfusion injury. Cellular water was quantified by multinuclear nuclear
      magnetic resonance (NMR) spectroscopy in isolated rat hearts during 30 min of
      ischemia and reperfusion. An increase in extracellular calcium from 0.75 to 2.25
      mM increased ischemic swelling twofold, with a marginal effect on functional
      recovery at reperfusion. Inhibition of Ca2+ channels with verapamil and bepridil
      reduced ischemic swelling by 58-66% and improved cardiac viability and functional
      recovery. Inhibition of the Na/Ca exchange with amiloride resulted in reperfusion
      swelling resulting from the inhibition of calcium efflux via the Na/Ca exchange.
      This was confirmed by inhibition with amiloride of 63% of cellular swelling
      induced by calcium overload via the Na/Ca exchange after calcium-free perfusion
      (calcium paradox). The volume-related activity of amiloride was attributed to the
      inhibition of Na/Ca exchange because the inhibition of the Na/H antiport resulted
      in low cellular volumes. The consistent changes in cellular volumes induced by
      the various agents used to alter calcium fluxes provide evidence of a pro
      edematous effect of intracellular calcium accumulation during myocardial
      ischemia. The administration of toxic doses of bepridil to the perfused and
      ischemic heart resulted in the shrinkage of cellular volumes and in functional
      failure. The toxicity of bepridil was mediated by unrestricted release of calcium
      from the sarcoplasmic reticulum because magnesium cardioplegia, which limits
      calcium release, lowered ischemic swelling without cellular shrinkage and
      improved functional recovery. In all experimental groups, cellular edema subsided
      during the early stages of reperfusion, indicating efficient dissipation of
      intracellular hyperosmolarity. There was no evidence that cytotoxic edema
      develops during ischemia or reperfusion, or both. On the contrary, calcium
      mediated cardiac toxicity was associated with cellular volume shrinkage as a
      result of the efflux of osmolytes through permeabilized sarcolemmal membranes. It
      is concluded that calcium ion is involved in the regulation of cellular volumes,
      and its intracellular accumulation promotes swelling in ischemic myocytes with
      intact membranes.

PMID- 12213995
TI  - The influence of gender, diabetes, and acetaldehyde on the intrinsic contractile
      properties of isolated rat myocardium.
AB  - Diabetes is associated with ventricular dysfunction. Ethanol consumption
      increases the risk of cardiovascular disease among diabetics. Acetaldehyde (ACA),
      the main ethanol metabolite, depresses cardiac contraction and contributes to
      ethanol-induced cardiac dysfunction. This study examined the influence of gender
      and diabetes on ACA-induced myocardial dysfunction. Adult male and female rats
      were made diabetic with streptozotocin (55 mg/kg). Left ventricular papillary
      muscles were isolated and stimulated to contract at 0.5 Hz. The mechanical
      parameters measured were peak tension development, time-to-peak tension (TPT),
      time-to-90% relaxation (RT90), and maximum velocities of tension development and
      decline (+/-VT). TPT and RT90 were comparably similar between genders. The +/-VT
      appeared to be slower in myocardium from female rats when compared to that of
      male counterparts, although the difference was not significant. Experimental
      diabetes elicited severe hyperglycemia, cardiac hypertrophy, hepatomegaly, and
      renal hypertrophy in both male and female animals. Myocardial mechanical
      properties exhibited prolonged TPT and RT90 in diabetic myocardium from both
      genders. The +/-VT was significantly reduced by diabetes in male but not in
      female myocardium. Acute ACA exposure decreased myocardial tension development
      and the +/-VT and shortened TPT and RT90 in myocardium from normal and diabetic
      rats of both genders. The ACA-induced depressant response on tension development
      was slightly enhanced by the diabetic state. In conclusion, these data suggest
      that the development of diabetes-induced myocardial dysfunction is similar
      between male and female animals and that the ACA-induced myocardial depressant
      action may be affected by diabetes but not by gender.

PMID- 12213996
TI  - Myocardial oxidative stress and antioxidants in hypertension as a result of
      nitric oxide synthase inhibition.
AB  - Rats were made hypertensive by the administration of the nitric oxide synthase
      inhibitor nitro-L-arginine (LNA, 2.74 mmol/L) in drinking water for 7 d. Hearts
      from hemodynamically assessed animals were analyzed for lipid peroxidation (LPO),
      gamma-glutamylcysteine-synthetase (gamma-GCS), glutathione disulfide reductase
      (GR), glutathione peroxidase (GSHPx), catalase (CAT), superoxide dismutase (SOD),
      and total radical trapping potential (TRAP) activities. LNA treatment increased
      the mean arterial blood pressure by 46% and the heart rate by 22% without
      changing plasma renin activity. LNA treatment resulted in a 30% increase in LPO.
      gamma-GCS was reduced by 48% and GR by 36% in the cardiac tissue of hypertensive
      rats as compared to controls. The activity of nonselenium GSHPx was reduced by
      27%, and selenium-dependent GSHPx activity in the heart was not affected by LNA
      treatment. In hypertensive rats, SOD activity was increased by 16%, and CAT was
      decreased by 46%. TRAP was lower (27%) in the myocardium of hypertensive rats
      than in that of controls. These data suggest that LNA-induced hypertension is
      associated with increased myocardial oxidative stress.

PMID- 12213997
TI  - Cultured rat vascular smooth muscle cells are resistant to methylamine toxicity:
      no correlation to semicarbazide-sensitive amine oxidase.
AB  - Methylamine (MA), a component of serum and a metabolite of nicotine and certain
      insecticides and herbicides, is metabolized by semicarbazide-sensitive amine
      oxidase (SSAO). MA is toxic to cultured human umbilical vein and calf pulmonary
      artery endothelial cells. Endothelial cells, which do not exhibit endogenous SSAO
      activity, are exposed to SSAO circulating in serum. In contrast, vascular smooth
      muscle cells (VSMC) do exhibit innate SSAO activity both in vivo and in vitro.
      This property, together with the critical localization of VSMC within the
      arterial wall, led us to investigate the potential toxicity of MA to VSMC.
      Cultured rat VSMC were treated with MA (10-5 to 1 M). In some cultures, SSAO was
      selectively inhibited with semicarbazide or MDL-72145 [(E)-2-(3,4
      dimethoxyphenyl)-3-fluoroallylamine]. Cytotoxicity was measured via MTT, vital
      dye exclusion, and clonogenic assays. MA proved to be toxic to VSMC only at
      relatively high concentrations (LC(50) of 0.1 M). The inhibition of SSAO with
      semicarbazide or MDL-72145 did not increase MA toxicity, suggesting that the
      production of formaldehyde via tissue-bound, SSAO-mediated MA metabolism does not
      play a role in the minimal toxicity observed in isolated rat VSMC. The omission
      of fetal calf serum (FCS), which contains high SSAO activity, from media
      similarly showed little effect on cytotoxicity. We conclude that VSMC--in
      contrast to previous results in endothelial cells--are relatively resistant to MA
      toxicity, and SSAO does not play a role in VSMC injury by MA.

PMID- 12213998
TI  - Butanedione monoxime increases the viability and yield of adult cardiomyocytes in
      primary cultures.
AB  - Various protocols for the isolation and cultivation of adult rat cardiomyocytes
      were compared, and the cytoprotective potential of the reversible myosin ATPase
      inhibitor butanedione monoxime (BDM) was evaluated based on cell yield, cell
      vitality, lactate dehydrogenase (LDH) and creatine kinase (CK) release, and the
      mRNA expression of atrial natriuretic peptide (ANP). Overall, a yield of 11.9 x
      10(6)cells with >92% cell vitality was obtained when BDM was added to the
      isolation and cultivation buffers. In contrast, cell vitality ranged from 30% to
      70% and cell yield was (4-10) x 10(6) when standard methods for the isolation of
      cardiomyocytes were used. Butanedione monoxime, at a 15 mM concentration, was
      cytoprotective during the isolation and cultivation of heart muscle cells, as
      judged by the morphological appearance (rod shape, lack of bleb formation, and
      other cytoskeleton defects) and the mRNA expression of the ANP gene. The
      activities of LDH and CK were also significantly reduced (p < 0.05%) when BDM was
      added to the isolation and cultivation buffer. The results obtained with BDM
      warrant further investigation into its cytoprotective potential during ischemia
      and damage to the cytoskeleton.

PMID- 12213999
TI  - Increased Expression but Reduced Activity of Antioxidant Enzymes in Alzheimer's
      Disease.
AB  - A growing body of data suggests that free radicals are involved in the
      pathogenesis of Alzheimer's disease (AD). Increased expression of antioxidant
      enzymes, such as superoxide dismutase (SOD), and their co-localization to senile
      plaques and dystrophic neurites have established a firm association between free
      radical mediated injury and the disease neuropathology. While several studies
      have confirmed these findings, there is conflicting information regarding the
      activity of some of the enzymes. In the current report, we assayed the activity
      of superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) from
      the same areas of the tissue showing increased expression of SOD1 and SOD2
      (parallel sequential slices). Nine brains with neuropathologically confirmed AD
      and six neuropathologically normal, age-matched, controls were examined. Despite
      marked increased expression of SOD1 and SOD2 within senile plaques in all the
      cases studied, the activities of SOD, GSH-Px and catalase were significantly
      lower in AD than in control brains. The difference was most profound in the case
      of catalase followed by GSH-Px and SOD. These data are in qualitative agreement
      with that of several laboratories, and support a decrease rather than an
      increase, in antioxidant enzyme activity. The findings suggest two main
      possibilities. On one hand, the observed reduced activity along with
      antigenically increased expression may be consistent with inactivation of excess
      protein that has been synthesized under conditions of high oxidative stress.
      Increased protein oxidation coupled with enzyme inactivation is a documented,
      aging-associated phenomenon. Alternatively, the increased immuno-reactivity may
      reflect a redistribution phenomenon as the enzymes become more concentrated at
      the sites of increased oxidative stress, despite an over all reduction in their
      activity.

PMID- 12214000
TI  - Androgens Prevent the Heat Shock-Induced Hyperphosphorylation but not
      Dephosphorylation of t in Female Rats. Implications for Alzheimer's Disease.
AB  - We have previously shown that heat shock induces rapid dephosphorylation of tau
      in both female and male rats followed by hyperphosphorylation only in female rats
      (J Neurochem 66 (1996), 1140-1149). We have also shown that the heat shock
      induced hyperphos-phorylation of tau is estrogen-independent in female rats and
      prevented by androgens in male rats (Proc Natl Acad Sci USA 94 (1997), 6612
      6617). To investigate whether androgens could prevent the hyperphosphorylation of
      tau also in female rats, twenty-three 2- to 3-month-old Sprague-Dawley rats were
      ovariectomized and given daily subcutaneous injections of 1 mg/250 g of
      testosterone propionate for 3-5 weeks. Immunoblots of SDS cerebral extracts were
      analysed qualitatively using the peroxidase-antiperoxidase technique and
      phosphate-dependent and -independent anti-tau antibodies, and quantitatively
      using Tau-1 and 125I-labeled protein A. We have found that while at 0 h after
      heat shock tau was dephosphorylated, at 3 h and 6 h after heat shock tau was not
      hyperphosphorylated, as would be the case in non-androgen-treated female rats
      (ref. above). In addition, tau became dephosphorylated in non-heat-shocked
      control rats. Because tau is abnormally hyperphosphorylated in Alzheimer's
      disease, the possibility of using combined estrogen/androgen replacement therapy
      in postmenopausal women as a preventive measure against Alzheimer's disease
      should be investigated.

PMID- 12214001
TI  - Apolipoprotein Serum Amyloid A in Alzheimer's Disease.
AB  - Alzheimer's disease is characterized by the tissue deposition of beta-amyloid
      peptide (Abeta) in the brain. Recent studies have shown apoproteins (apo) in
      amyloid plaques and associated with high-density lipoprotein (HDL) particles in
      the cerebrospinal fluid (CSF). Western blot analysis revealed that serum amyloid
      A (apoSAA) protein was present in control and AD patients at low levels compared
      to apoE and apoA-I, however, AD brains showed a significant increase over control
      values. Analysis of CSF-HDL from control and AD individuals showed that apoA-I,
      apoE and apoSAA were on the particle. Immuno-cytochemical analysis showed that
      SAA was detected in senile plaques in AD tissue, but was predominantly localized
      to neuritic plaques. ApoE staining of AD brain confirmed that most plaques
      contained the apoprotein, similar to Abeta immunoreactivity, whereas apoA-I
      expressed little staining of senile plaques. No significant differences were
      detected in the level of apoSAA when compared to APOE genotype in AD samples,
      suggesting that interactions with apoE were non-specific. These data imply that
      the specific interactions of SAA with Abeta in the neuritic plaques may play a
      role in AD.

PMID- 12214002
TI  - Phosphorylation Activity in the Alzheimer's Disease and Normal Brain is Modulated
      by Microtubule-Associated Protein, Tau in Vitro.
AB  - One of the hallmarks of Alzheimer's Disease is the presence of abundant
      neurofibrillary tangles (NFTs) in the brains of affected individuals.
      Hyperphosphorylated tau is a major component of paired helical filaments (PHFs)
      in NFTs. Tau is a neuronal microtubule associated protein found primarily in
      axons. Normal tau promotes tubulin polymerization and stabilizes microtubule (MT)
      structures, whereas hyperphosphorylated tau reduces its affinity for MTs and
      destabilizes MT-structures. This results in the disruption of vital cellular
      processes (e.g. axonal transport) and leads to the degeneration of affected
      neurons. Processes leading to the hyperphosphorylation of tau and formation of
      neurofibrillary lesions in Alzheimer's Disease (AD) brains are not understood.
      Phosphorylation of a substrate molecule like tau depends upon the equilibrium
      between kinase and phosphatase activities and the availability of their substrate
      molecules in a given system. Therefore, to understand the relative roles of
      kinase and phosphatase activities, we studied the long-term kinetics of
      phosphorylation in AD and control brain extracts in the presence and absence of
      the phosphatase inhibitor okadaic acid (OA) using histone, casein and bacterially
      expressed tau as exogenous substrates. It was found that both kinase and
      phosphatase activities were higher in AD compared to control brains.
      Surprisingly, between 18 and 24 hours, there was a robust increase in
      phosphorylation of endogenous proteins in the brain extracts only when
      bacterially expressed tau was present in the phosphorylation reaction mixture.
      This pattern of phosphorylation activity was unaffected by OA. Significant
      difference in the phosphorylation of tau isoforms was also seen during this
      period. These data suggest that the expression and differential phosphorylation
      of certain tau isoforms may be responsible for the robust increase in
      phosphorylation and may play an important role in Alzheimer's pathology.

PMID- 12214003
TI  - Brain Accumulation of Amyloid-beta in Non-Alzheimer Neurodegeneration.
AB  - We report an unusual case of amyotrophic lateral sclerosis (ALS) marked by
      extensive cerebral amyloid-beta deposition in small and medium-size vessels,
      capillaries, and perivascular plaques in the cerebral cortex, and in most
      leptomeningeal vessels. Despite considerable cerebral amyloidosis, the patient
      remained cognitively intact until death. For comparison with other neuro
      degenerative diseases and normal aging, we assessed the densities of amyloid-beta
      immunoreactive cortical vessels and plaques in matched frontal and temporal lobe
      sections from archival uncomplicated cases of Alzheimer's disease (N=10), Pick's
      disease (PkD; N=4), Parkinson's disease (PD; N=6), Diffuse Lewy body disease
      (DLBD; N=7), progressive supranuclear palsy (PSP; N=5), multiple systems atrophy
      (MSA; N=4), ALS (N=7), or normal aging (N=10) by semi-quantitative grading (0 to
      3+). Moderate (2+) or abundant (3+) cerebrovascular amyloid-beta immunoreactivity
      was detected in 8/10 AD, 3/7 DLBD, 3/6 PD, 1 each with PSP or PkD, and 2/10
      controls. Moderate or abundant densities of amyloid-beta-immunoreactive diffuse
      plaques were detected in all cases of AD or DLBD, 4/6 with PD, 3/5 with PSP, and
      2/10 controls. Moderate or abundant amyloid-beta-immunoreactive mature (dense
      core) plaques were present in all cases of AD or DLBD, and 3 each with PD or PSP.
      Importantly, amyloid-beta-immunoreactivity was not observed in the 4 MSA or 7
      archival ALS cases. This study demonstrates that prominent amyloid-beta
      accumulation in cerebral vessels and plaques occurs frequently in AD, DLBD, PSP,
      and PD, but not in ALS or MSA, indicating that the case described is unique. The
      lack of cognitive impairment in the case presented argues against the idea that
      extensive amyloid-beta deposition in the brain causes dementia.

PMID- 12214004
TI  - Lipopigment Changes in Purkinje Cells in Alzheimer's Disease.
AB  - Cerebellar tissue was examined from 22 patients with Alzheimer's disease (AD) and
      from an age-matched group of 20 non-diseased subjects. Intraneuronal lipopigment
      in the bodies of 1344 Purkinje cells (PCs) (32 per brain) was identified by
      fluorescence microscopy. The mean total area (per PC) of the outlines of discrete
      regions of lipopigment in a PC perikaryon for the AD-related group of PCs was
      significantly greater than the mean for the comparison group (p<0.001). Also, the
      two groups of PCs showed significant (</=0.05) differences in the mean number
      (per PC) of discrete regions of lipopigment in 11 size categories. The findings
      indicate a lysosomal abnormality in PCs in AD. The pattern of size distribution
      of lipopigment in PCs differed from that previously-reported for neurons of the
      frontal cortex. These differences may be associated with the absence of senile
      plaques and the presence of "diffuse" amyloid plaques in the cerebellum in AD

PMID- 12214005
TI  - Alzheimer's Disease Pathology in Non-Demented Elderly.
AB  - The purpose of this study was to quantitate the extent of neuropathological
      lesions (neurofilbrillary tangles and senile plaques) characteristic of
      Alzheimer's disease in cognitively intact elderly control subjects. The subjects
      included twenty-six elderly individuals who were autopsied at a university-based
      Alzheimer's Disease Center. The mean age at autopsy was 78 years (range 51-99
      years); there were 15 males and 11 females. All of these control subjects had a
      few neurons containing neurofibrillary tangles in the hippocampus, but no
      neurofibrillary tangles in the neocortex. Twelve of the 26 subjects (46%) had
      some senile plaques in the neocortex, while fourteen (54%) did not. Six subjects
      (23%) had substantial numbers of senile plaques in the neocortex. Neither the
      number of neurons containing neurofibrillary tangles nor the number of senile
      plaques correlated with age in these subjects. Possible conclusions are that
      there are many elderly individuals with incipient Alzheimer's Disease, or that
      one can have some degree of these lesions and still be cognitively normal. These
      data point out the need to have better pathological markers of the disease
      process and better diagnostic criteria to define Alzheimer's Disease.

PMID- 12214006
TI  - Regional Neuropeptide Pathology in Alzheimer's Disease: Corticotropin-Releasing
      Factor and Somatostatin.
AB  - BACKGROUND: the neuropeptides most consistently reported to be altered in
      Alzheimer's disease are corticotropin-releasing factor and somatostatin
      (somatotropin-release inhibiting factor), although this has been previously
      assessed in a limited number of brain regions. METHODS: in order to
      comprehensively characterize the involvement of these two anatomically distinct
      neuropeptide systems in Alzheimer's disease and to determine if they are equally
      involved in the associated pathology, we measured the concentration of
      corticotropin-releasing factor and somatostatin in post-mortem brain tissue.
      Radioimmunoassay of 24 cortical and 13 sub-cortical brain regions from 16 cases
      of neuropathologically confirmed AD and 9 non-Alzheimer's disease controls were
      performed and significant differences in group regional neuropeptide
      concentrations were sought using the Student Newman-Keuls test after ANOVA.
      RESULTS: comparison of group mean regional neuropeptide concentrations revealed
      several brain regions where both peptides were decreased in Alzheimer's disease
      and some regions where only one of the two peptides were decreased, while still
      other regions exhibited no changes in either peptide. These changes were
      principally found in frontal and temporal cortex, with few subcortical regions
      exhibiting pathologic changes in peptide concentration. Regional peptide content
      was correlated among peptides and with duration of dementia in several brain
      regions. CONCLUSIONS: these data support the hypothesis that the somatostatin-
      and corticotropin-releasing factor containing neurons are pathologically involved
      in AD and that the involved neurons are limited to specific areas of the brain.

PMID- 12214007
TI  - Activity of Hippocampal CA1 Neurons in Alzheimer's Disease is not Affected by the
      Presence of Adjacent Neuritic Plaques.
AB  - Alzheimer's disease (AD) is neuropathologically characterized by neuritic plaques
      (NPs) and neurofibrillary tangles and functionally by a decreased metabolic rate
      of neurons. Our previous studies showed that in brain areas which are extensively
      affected by plaques and tangles, i.e. the CA1 area of the hippocampus and the
      hypothalamic tuberomamillary nucleus, neuronal protein synthetic ability is
      significantly lower in AD patients than in controls. However, the presence of
      tangles as shown by Bodian staining appeared not to be directly related to
      decreased protein synthetic ability of neurons. In order to study to what extent
      the metabolic function of neurons might be affected by the other
      neuropathological hallmark of AD, i.e. NPs, which are presumed to contain
      neurotoxic compounds, we studied eight severely demented AD patients matched for
      the ApoE genotype (ApoE 3/3). Using an image analysis system, the size of the
      neuronal Golgi apparatus (GA) and of the cell profile area was measured as a
      parameter for protein synthetic activity in the CA1 area of these patients. NPs
      were stained by Bodian, and subsequently the distance of each neuron with an
      immunostained GA to the nearest NP was measured. Our results showed that neither
      NP density nor the distance between NPs and neurons correlated with the protein
      synthetic ability of neurons as judged by the size of the GA. Based on these
      results we suggest that in AD the presence of NPs and decreased neuronal protein
      synthetic ability are basically two independent phenomena

PMID- 12214008
TI  - Cerebrovascular Pathology Contributes to the Heterogeneity of Alzheimer's
      Disease.
AB  - Heterogeneous pathology in Alzheimer's Disease (AD) is due to variability in the
      nature and severity of lesions, overlap with other neurodegenerative diseases
      such as Parkinson's disease, or the co-existence of cerebrovascular disease. In
      the MGH-ADRC autopsy archives, remote cerebral infarcts (CVA) were reported in
      30% of the otherwise uncomplicated AD cases. To determine the potential
      significance of cerebrovascular lesions in relation to AD, the relative densities
      (CERAD grading criteria) of Bielschowsky-stained AD lesions and Ab-amyloid
      immunoreactive plaques were compared among cases of AD+CVA (N=52), AD (N=48),
      aged controls (NC; N=9), and aged controls with AD lesions (ADC; N=8). The
      prevalence of the ApoE varepsilon 4 allele was also determined for each group.
      This study demonstrated: 1) higher densities of Bielschowsky-stained plaques in
      AD, AD+CVA, and ADC than in NC (P<0.0001); 2) more abundant neurofibrillary
      tangles in AD relative to all other groups (P<0.0005), and in AD+CVA and ADC
      relative to NC (P<0.05); and 3) increased densities of Ab-amyloid-immunoreactive
      plaques in AD relative to AD+CVA (P=0.0003). In AD+CVA, cerebral vascular lesions
      consisting of remote microscopic cortical and subcortical white matter infarcts,
      ischemic lesions, and leukoaraiosis were consistently distributed in structures
      typically damaged by AD neurodegeneration, as well as in the basal ganglia. The
      ApoE varepsilon 4 allele was more prevalent in the AD+CVA (70%) than in the AD
      (58%) group (P=0.05). Since the AD and AD+CVA groups had similar degrees of
      dementia, the results suggest that cerebral vascular lesions in regions typically
      destroyed by AD may contribute to the clinical manifestations of AD.

PMID- 12214009
TI  - Bursting Dense Microspheres (Spherons) in Alzheimer's DiseaseA Review of Studies
      (1980-1997) on Spherons and the Pathogenesis of Alzheimer's Disease.
AB  - This paper reviews our research studies during the past 17 years on the
      relationship of cerebral protein dense microspheres (DMS), termed spherons, and
      senile plaques (SP) in the aged human brain and in AD. Initially, correlative
      anatomical and pathological data suggested that spherons may evolve into SP. This
      led to morphometric studies which strongly supported the theory. Biochemical
      studies were undertaken which showed that spherons could be isolated to
      homogeneity from brain tissue and contained the markers associated with SP.
      Experiments in vitro with spherons, and with inoculation of spherons into
      animals, reproduced SP lesion characteristics. To test the validity of using
      spherons for drug screening, experimental drugs were tested, a few of which are
      capable of blocking the formation of spheron-induced experimental SP.

PMID- 12214010
TI  - Delivery of Nerve Growth Factor to the Brain via the Olfactory Pathway.
AB  - Purpose: To assess the potential of delivering nerve growth factor (NGF) to the
      brain along the olfactory neural pathway for the treatment of Alzheimer's
      disease. Methods: Recombinant human NGF (rhNGF) was given as nose drops to
      anesthetized rats. The rhNGF concentrations in the brain were determined by
      enzyme-linked immunosorbent assay (ELISA). Results: Following olfactory
      administration, rhNGF reached the brain within an hour, achieving a concentration
      of 3400 pM in the olfactory bulb, 660-2200 pM in other brain regions and, 240 pM
      and 180 pM in the hippocampus and the amygdala, respectively. In contrast, little
      or no rhNGF was found in the brain following intravenous administration.
      Conclusions: A significant amount of rhNGF can be delivered to the brain via the
      olfactory pathway. The detection of rhNGF by ELISA indicates that rhNGF is
      delivered to the brain relatively intact. The rapid appearance of rhNGF in the
      brain suggests that it may be transported by an extraneuronal route into the
      brain via intercellular clefts in the olfactory epithelium. Further work to
      clarify the transport mechanism is underway. The olfactory pathway is a
      promising, non-invasive route for drug delivery to the brain, which has potential
      for the treatment of neurodegenerative diseases including Alzheimer's disease.

PMID- 12214011
TI  - Reactive Oxygen Species Mediate Cellular Damage in Alzheimer Disease.
AB  - The two most striking features of Alzheimer disease are (i) the multitude of
      abnormalities affecting essentially every system and (ii) the strict age
      dependence. Recent work suggests that both features are linked to increased
      oxidative stress that damages lipids, proteins and nucleic acids and results in
      redox-active metal accumulations, mitochondrial damage and formation of advanced
      glycation endproducts. Interestingly, beta-protein precursor, amyloid-beta,
      presenilins, and apolipoprotein E have all been linked to reactive oxygen species
      production or apoptosis, a process intimately associated with oxidative stress.
      In therapeutics, the commonality between a number of efficacious agents appears
      to be oxidative stress reduction. Therefore, we contend that oxidative stress is
      the element that links the multitude of changes in Alzheimer disease and that a
      reduction of oxidative stress will have a dramatic effect on reducing the
      incidence or progression of Alzheimer disease.

PMID- 12214012
TI  - Bismuth Toxicity Masquerading as Alzheimer's Dementia.
AB  - A 76-year old white married female had rapid onset dementia with myoclonus and
      was admitted to an HMO hospital where she was initially diagnosed as Alzheimer's
      disease. The physician- husband suggested that the condition might be due to the
      Pepto-Bismol which she had taken chronically to control her irritable bowel
      syndrome. An elevated serum bismuth level of 242 &mgr;g/L (normal is 5 &mgr;g/L)
      established bismuth toxicity as the cause of the dementia. With treatment the
      patient returned to a normal mental state. The possibility of bismuth
      encephalopathy needs to be considered in the differential diagnosis of possible
      Alzheimer's dementia.

PMID- 12214013
TI  - Astrocytosis, microgliosis, metallothionein-I-II and amyloid expression in high
      cholesterol-fed rabbits.
AB  - Cholesterol is considered a risk factor in vascular dementia as well as in
      Alzheimer's disease. Several biochemical, epidemiological and genetic aspects
      established a correlation between cholesterol concentration and Alzheimer's
      disease. Microglia activation, astrocytosis with metallothionein-I-II
      overexpression, amyloid beta intraneuronal accumulation and a rare formation of
      amyloid beta extracellular positive deposits were the major immunohistochemical
      features observed in the brain of high cholesterol-fed animals. The relevance on
      the cholesterol metabolism in Alzheimer's disease pathogenesis is also discussed.

PMID- 12214014
TI  - Brainstem and cortical Lewy bodies in patients presenting clinically with
      Alzheimer's disease.
AB  - In order to study the clinical overlap between neuropathologically defined Lewy
      body disease (LBD) and Alzheimer's disease, we examined the brains of 37 demented
      and 13 non-demented subjects. Nigral Lewy bodies (LBs) were present in 16/37
      dementia patients, 13 of which had LBD. Eight of these 13 were clinically
      indistinguishable from AD patients, and in these cases isocortical
      neurofibrillary tangle (NFT) formation was rare. Thus, although the two
      conditions were clinically similar in this series, LBD could be distinguished
      from AD pathologically not only by the presence of nigral LBs but also by the
      relative paucity of isocortical NFTs.

PMID- 12214015
TI  - Cerebrospinal fluid lipoprotein delivery to human neuronal cells is increased in
      Alzheimer's disease and is dependent on apoE monomer concentration.
AB  - Recent studies of cerebrospinal fluid (CSF) have shown increased oxidation of CSF
      lipoproteins in Alzheimer's disease (AD) patients, and neurotoxicity from
      oxidized CSF lipoproteins in culture. Since inheritance of different alleles of
      the apolipoprotein (apo) E gene is a risk factor for AD and apoE is the major
      lipoprotein trafficking molecule in brain, we hypothesized that apoE may modify
      the pathogenesis of AD by directing the delivery of oxidized CSF lipoproteins to
      neurons. To test this hypothesis, we adapted a method previously used with
      isolated plasma lipoproteins to specifically label lipid particles in situ in
      native CSF and quantified their delivery to human SK-N-BE(2)C neuroblastoma
      cells. CSF lipoproteins were delivered to neuronal cells largely through apoE
      dependent processes. Importantly, CSF lipoproteins from AD patients were
      delivered more efficiently than CSF lipoproteins from age-matched controls; this
      effect was not associated with apoE genotype or degree of CSF lipoprotein
      oxidation but was associated with apoE monomer concentration that tended to be
      lower in AD patients. The inverse relationship between apoE monomer concentration
      and CSF lipoprotein delivery was duplicated in SK-N-BE(2)C cells, but not human
      astrocytoma cells, using artificial lipid particles and purified human apoE.
      These results suggest that lipoproteins in CSF from AD patients are delivered
      more efficiently to neurons than are CSF lipoproteins from controls, and that
      this abnormality may be explained largely by variations in CSF apoE
      concentration.

PMID- 12214017
TI  - AbetaPP, apoptosis and Alzheimer's disease.

PMID- 12214018
TI  - Differential efficacy of lipophilic and cytosolic antioxidants on generation of
      reactive oxygen species by amyloid-beta.
AB  - Exposure of neurons to amyloid-beta (Abeta) is accompanied by a cascade of
      oxidative damage that initiates with lipid peroxidation followed by subsequent
      generation of cytosolic free radicals and reactive oxygen species (ROS). The
      antioxidant vitamin E has been utilized to counteract Abeta-induced oxidative
      stress. We considered herein whether or not the lipid-solubility of vitamin E
      limits its neuroprotection to membrane-related oxidative damage, and renders it
      relatively ineffective where prior lipid peroxidation has already generated
      cytosolic free radicals and ROS. To test this possibility, we treated
      differentiated SH-SY-5Y human neuroblastoma with vitamin E or a cell-permeant
      antioxidant, N-acetyl cysteine (NAC), simultaneously with or 15 min after the
      application of Abeta. Both vitamin E and NAC prevented Abeta-induced ROS
      generation when applied simultaneously with Abeta, but only NAC prevented Abeta
      induced ROS generation when added to cultures that had previously been exposed to
      Abeta. These results support the hypothesis that vitamin E can quench Abeta
      induced lipid peroxidation, but cannot effectively quench ROS generated by prior
      lipid peroxidation. These findings in cell culture may provide limited insight
      into why vitamin E is not fully effective against neurodegeneration in AD in
      clinical settings, since some neuronal populations are likely to already have
      been compromised by prior Abeta exposure before vitamin E treatment was
      initiated.

PMID- 12214016
TI  - Neuronal apoptosis is accompanied by amyloid beta-protein accumulation in the
      endoplasmic reticulum.
AB  - A series of evidences suggests that enhanced susceptibility to programmed cell
      death (PCD) is a major pathogenetic factor in Alzheimer's disease (AD). We
      investigated this issue, analyzing amyloid beta-protein (A beta) production in a
      model of neuronal PCD, induced by staurosporine in a murine neuroblastoma cell
      line. When PCD was induced, a 280-290% secreted A beta occurred, in spite of a
      20% metabolism and an unchanged A betaPP expression. The increased intracellular
      A beta reactivity largely colocalized with a marker of ER. Inhibition of caspases
      blocked the cleavage at the C-terminus of beta PP, but only partially rescued A
      beta overproduction caused by staurosporine treatment. Our findings suggest that
      PCD fosters the physiological pathways of A beta production characteristic of
      neuronal cells, and they confirm the theory that unbalance of PCD is a central
      event in AD pathogenesis. Moreover, our data indicate that still unidentified
      cellular mechanisms, other than caspases activation, are responsible of the
      specific alteration of A betaPP processing during PCD.

PMID- 12214019
TI  - Effect of long-term aluminum feeding on lipid/phospholipid profiles of rat brain
      synaptic plasma membranes and microsomes.
AB  - Long-term exposure to AlCl_3 resulted in 57% phospholipid (TPL) content of
      synaptic plasma membranes from rat brain with significant decrease in the
      proportion and content of most of the phospholipid classes (32%- decreases was of
      lesser magnitude for phosphatidylcholine (PC) and phosphatidylethanolamine (PE).
      The microsomal TPL and cholesterol (CHL) content decreased by 74% composition.
      However, the contents of all phospholipids decreased uniformly by about 70%.
      fluidized in Al fed rats. The results suggest that long-term exposure of rats to
      Al can alter the structure/function of synaptic plasma membranes and microsomes.

PMID- 12214020
TI  - Aluminum exposure and Alzheimer's disease.
AB  - The regulatory agencies of the United States and Canada have placed aluminum on
      priority lists for research designed to fill data gaps relating to neurotoxicity.
      This is to create a factual basis for the establishment of health standards for
      drinking water. In this review, we consider evidence for a significant role for
      aluminum in AD. Aluminum has been implicated as a potential risk factor in
      Alzheimer's Disease (AD) and for elderly cognitive impairment by epidemiology
      studies of drinking water and a food study. Most people experience aluminum brain
      overload in the aging process. Aluminum levels over 20 times higher than those of
      a middle-aged group were found in a brain autopsy study of elderly persons,
      roughly correlating over the age period with densities of senile plaques and
      neurofibrillary tangles. Persons with AD have been found to experience increased
      absorption of aluminum and higher blood levels. More controversially, the
      majority of brain studies also show elevated aluminum levels, though there is
      disagreement over location of metal buildup. Clinical intervention to lower brain
      aluminum by chelation has slowed the progression of AD.

PMID- 12214021
TI  - Aluminum and Alzheimer's disease.

PMID- 12214022
TI  - Dementia, depression and parkinsonism: A frequent association in the elderly.
AB  - Depression and parkinsonism constitute two frequent findings in elderly demented
      patients. A large body of research, including epidemiological, retrospective, and
      prospective studies have contributed to the understanding of complex and common
      situations in the elderly, in which depression, parkinsonian signs, and cognitive
      impairment coexist. Many aspects regarding the "associated syndromes of
      dementia", however, are still object of debate as well as under current active
      investigation. The recent dramatic aging of the population is leading to an
      increasing prevalence of neuropsychiatric comorbidities. This is a problem of
      great clinical and socio-economical interest, because, when present in the same
      subject, depression, parkinsonism-related motor impairment and cognitive
      impairment may not only act additively or synergistically in deteriorating the
      functional outcome of the patient, but also lead to their institutionalization.
      We observed that one half of institutionalized subjects in two nursing homes of
      Central Italy suffer from an associated syndrome dementia / parkinsonism /
      depression, that these subjects are significantly more dependent than subjects
      hospitalized for the same reasons, and that their grade of depression or
      cognitive impairment is independent of which disease is diagnosed first.
      Depressed mood, memory impairment and motor difficulties, however, are often
      underestimated in the elderly, being considered as "normal" aspects of the aging
      process. The aim of this review is to highlight the clinical relevance of the
      associated syndromes of dementia, in a way that early diagnosis and treatment of
      these pathologies are attempted.

PMID- 12214023
TI  - Modifications of tau protein during neuronal cell death.
AB  - Accumulation of hyperphosphorylated tau protein and progressive neuronal loss are
      among the major hallmarks of certain neurodegenerative disorders including
      Alzheimer's disease. However, the relationship between tau phosphorylation and
      neuronal cell death remains unclear. Here we have analyzed tau modifications
      during two forms of neuronal death, apoptosis and necrosis, using primary
      cultures of cerebellar granule neurons as a simple model system. Induction of
      neuronal apoptosis by inhibition of phosphatidylinositol 3-kinase results in a
      rapid increase in the phosphorylation of tau, which is followed by the
      dephosphorylation and cleavage of the protein. In contrast, necrosis triggered by
      high salt shock or glutamate treatment leads to a rapid dephosphorylation and an
      almost complete proteolysis of tau. These data suggests that a transient tau
      hyperphosphorylation occurs at an early stage of apoptosis, whereas tau is
      dephosphorylated and cleaved during the late phase of apoptosis as well as in
      necrotic neurons.

PMID- 12214024
TI  - Limited proteolysis of NACP/alpha-synuclein.
AB  - The NAC region of NACP/alpha-synuclein is a secondary component of Alzheimer's
      disease amyloid. alpha-Synuclein is a major component of Lewy bodies, a typical
      neuropathological feature of Parkinson's disease. However, the physiological role
      and deposition mechanisms of alpha-synuclein are unknown. Structural analyses of
      alpha-synuclein should provide a better understanding of its biochemical
      characteristics. We investigated the digestion of alpha-synuclein withalpha
      chymotrypsin and cathepsin D, which are reported to be involved in
      amyloidogenesis, under various conditions in vitro. There are many putative
      cleavage sites for these enzymes in alpha-synuclein, including in the NAC region.
      However, most of the predicted sites remained undigested, and the NAC region was
      found to be intact even after extensive digestion. This peculiar characteristic
      of alpha-synuclein may be relevant to the abnormal deposition of this molecule in
      alpha-synuclein-associated neurodegenerative diseases.

PMID- 12214025
TI  - Blood pressure and dementia in persons 75+ years old: 3-year follow-up results
      from the Kungsholmen Project.
AB  - A community cohort of 1270 non-demented 75+ years old persons was followed to
      evaluate the influence of blood pressure on incidence of dementia. Two hundred
      and eighteen dementia cases were detected during an average of three years of
      follow-up. Subjects with baseline systolic pressure >/= 180 mm Hg had an age- and
      gender-adjusted relative risk (RR) of 1.6 (95% to persons with systolic pressure
      of 141-160 mm Hg. This association persisted, although not statistically
      significant, when education, vascular diseases, and antihypertensive drug use
      were entered in the model (RR = 1.4; 95% systolic pressure were not related to
      dementia incidence. However, individuals with a decrease of 5--19 mm Hg and >/=
      20 mm Hg in systolic pressure from baseline to follow-up had a RR of 1.8 (95%
      2.6) and 2.5 (95% also found in subjects with diastolic pressure reduction. In
      conclusion, our findings support an association between high systolic pressure
      and increased risk of dementia, whereas blood pressure reduction may be secondary
      to the dementia process itself.

PMID- 12214026
TI  - Uncoupling of mitochondria activates protein phosphatases and inactivates MBP
      protein kinases.
AB  - Dephosphorylation of PHF-tau was observed in carbonyl cyanide p
      (trifluoromethoxy) phenylhydrazone (FCCP)-treated, but not in oligomycin-treated
      undifferentiated PC12 cells. FCCP depletes ATP levels by uncoupling oxidative
      phosphorylation and increases cytosolic calcium levels, while oligomycin inhibits
      the ATP synthase. We also observed inactivation of several myelin basic protein
      (MBP) kinases in FCCP-treated PC12 cells, using an in-gel kinase assay. In
      addition, several phosphotyrosine proteins were dephosphorylated following FCCP
      treatment. These studies suggest that MBP kinases and tyrosine phosphatase may be
      regulated by mitochondrial activity and they may regulate the phosphorylation
      state of tau. Since mitochondrial dysfunction occurs in Alzheimer disease, such
      changes in protein phosphorylation may well be relevant to the disease.

PMID- 12214027
TI  - CSF Abeta40 and Abeta42: Natural course and clinical usefulness.

PMID- 12214028
TI  - Normal levels of clusterin in cerebrospinal fluid in Alzheimer's disease, and no
      change after acute ischemic stroke.
AB  - The protein clusterin has been suggested to be involved in the pathogenesis of
      Alzheimer's disease (AD). Its expression is increased in brain regions affected
      by AD pathology, and to elucidate if there is a concomitant increase of clusterin
      also in the cerebrospinal fluid (CSF) in different neurological disorders, CSF
      samples from patients with AD, vascular dementia (VAD), Parkinson's disease (PD),
      and controls were analysed. Also longitudinal (five occasions) samples from
      patients with acute stroke were analysed, to follow any degenerative/regenerative
      phase after acute brain damage. However, there were no changes in CSF-clusterin
      levels from patients in AD, VAD, PD or acute stroke, as compared to controls. The
      increase of clusterin in brain tissue is suggested to reflect a regenerative
      response process, which here is shown not to be followed by a concomitant
      increase in the CSF. Thus, CSF-clusterin can not be used as an indicator or a
      diagnostic marker for AD.

PMID- 12214030
TI  - CommentaryCommentary on: The Characterization by Atomic Force Microscopy and
      Cryoelectron Microscopy of Tau Polymers assembled in Alzheimer's disease.

PMID- 12214029
TI  - Characterization by atomic force microscopy and cryoelectron microscopy of tau
      polymers assembled in Alzheimer's disease.
AB  - The structure of the Paired Helical filaments (PHF), a polymer of the microtubule
      associated protein tau, has been studied by Atomic Force Microscopy (AFM) and by
      cryoelectron microscopy. Mica and graphite were used as substrates in the AFM
      analysis with no differences in the results. A banding pattern of 8-12 nm width
      within the helical structure is found when detailed analysis of the data is
      performed. High AFM resolution images obtained by using an ultra sharp tip
      confirm the previous results and suggest that the structures observed are
      compatible with a helical ribbon made up of two parallel strands. These results
      were confirmed by cryoelectron microscopy experiments.

PMID- 12214031
TI  - A quantitative assessment of glycolipid and protein associated with paired
      helical filament preparations from Alzheimer's diseased brain.
AB  - Protease resistant paired helical filaments (prcPHF) can be isolated from the
      brains of Alzheimer's diseased patients. A second type of PHF, A68 PHF, may be
      extracted in soluble form from brain homogenate and induced to form filaments in
      vitro. Here we use a variety of analytical techniques to assess the protein,
      carbohydrate and fatty acid composition of prcPHF and A68 PHF. High-field ^1H NMR
      of both PHF preparations display similar fatty acid and carbohydrate proton
      resonances, consistent with the presence of a structurally similar glycolipid.
      Carbohydrate analysis showed that both preparations contained greater than 82%
      less than 12% C16:1 was significantly lower in A68 PHF than in prcPHF, both
      preparations contained otherwise similar fatty acid profiles with the most
      abundant lipid component being oleic acid (C18:1, 29.3 +/- 9.0%) followed by
      palmitic (C16:0, 28.5 +/- 5.6%) 17.6 +/- 7.5%) preparations revealed a profile
      reasonably consistent with that previously determined for PHF-tau but
      significantly higher in glycine and lower in lysine than would be predicted from
      the cDNA sequence. On a weight per cent basis, protein accounted for about 51%
      A68 PHF samples but only about 10% Carbohydrate and fatty acid accounted for
      about 39% A68 PHF samples but 74% preparations showed strong correlations between
      the total amount of tau protein and fatty acid. These results suggest that a
      glycolipid component forms an integral part of the PHF structure.

PMID- 12214033
TI  - Is hemochromatosis a risk factor for Alzheimer's disease?
AB  - Excess iron accumulation in the brain is a consistent observation in Alzheimer's
      Disease. Iron affects amyloid precursor protein (AbetaPP) processing and promotes
      deposition of Abeta. Iron is also among the most potent biological toxins because
      of its ability to react with oxygen to form reactive oxygen species.
      Consequently, elucidation of the mechanisms associated with maintaining brain
      iron homeostasis is fundamentally important to understanding the underlying
      pathogenesis in AD. The iron overload disorder, Hemochromatosis, is the most
      common genetic disorder (1:200) so a significant percentage of AD patients can be
      expected to carry this mutation. Heterozygotes for this mutation also have an
      increased, but sub-clinical iron burden. Given the high percentage of the
      population who are at significant risk for iron overload, we propose that the
      hemochromatosis mutation be considered as a confounding factor when evaluating
      the contribution of genetic associations with AD and treatment strategies and
      efficacy. Two recent papers and new evidence presented here that the protein
      associated with hemochromatosis is expressed on blood vessels, choroid plexus and
      the ependymal cells in the brain are offered as support for this proposal.

PMID- 12214034
TI  - Amyloid-beta promotes calcium influx and neurodegeneration via stimulation of L
      voltage-sensitive calcium channels rather than NMDA channels in cultured neurons.
AB  - Exposure of cultured neurons and neuronal cells to aggregated amyloid-beta
      (Abeta) induces multiple neurodegenerative events including accumulation of
      cytosolic calcium, generation of reactive oxygen species, abnormal levels of
      phosphorylation of the microtubule-associated protein tau, and apoptosis.
      Prevention of accumulation of calcium within the cytosol also prevents all other
      events, suggesting that calcium accumulation is an early and pivotal event in
      Abeta neurotoxicity. Calcium influx has been suggested to occur via L voltage
      sensitive calcium channels or NMDA channels. Calcium influx into differentiated
      human neuroblastoma cells has been previously attributed to the L voltage
      sensitive calcium channel, but the contribution of the NMDA channel was not
      examined. In the present study, treatment of these cells with MK-801, an
      antagonist of NMDA channels, failed to attenuate Abeta-induced calcium influx or
      neurodegeneration, while nimopridine, an antagonist of the L voltage-sensitive
      calcium channel, blocked Abeta-induced calcium influx. Our findings suggest that
      NMDA channels do not contribute significantly to Abeta neurotoxicity in these
      acute cell culture analyses.

PMID- 12214035
TI  - Characterization of the human alpha-synuclein gene: Genomic structure,
      transcription start site, promoter region and polymorphisms.
AB  - The human NACP/alpha-synuclein gene has been cloned. This gene consists of 6
      exons ranging in size from 42 to 1110 bp. The translation start codon ATG is
      encoded by exon 2 and the stop codon TAA is encoded by exon 6. The non-Abeta
      component of Alzheimer's disease amyloid (NAC) is encoded by exon 4. The two
      previously reported minor isoforms of NACP/alpha-synuclein, NACP112 [29] and
      NACP126 [6], are alternatively spliced products, in which exon 5 and exon 3 are
      spliced out, respectively. Exon 1 was found to have different splicing sites,
      producing different 5'-untranslated sequences in the cDNAs. A previously reported
      dinucleotide repeat polymorphic marker has been mapped to 8kb upstream of the
      transcription start site. A highly TC-rich sequence in intron 4 was found to be
      polymorphic by length and four alleles, A0, A1, A2 and B have been identified in
      the Caucasian population. Genotyping this polymorphism among pure Alzheimer's,
      Lewy body variant and Parkinson's subjects and aged normal control subjects did
      not reveal any significant differences.

PMID- 12214036
TI  - Alzheimer's disease-related synapse loss in the cingulate cortex.
AB  - Synapse loss is considered a profound neuropathology associated with Alzheimer's
      disease (AD). This AD-related change in connectivity can be demonstrated in many
      regions of the neocortex. The posterior cingulate cortex has been identified as
      an area involved early in the disease process but has not been well studied. The
      anterior cingulate cortex, which is morphologically distinct from the posterior
      cingulate, is also involved in AD. The present study employed ultrastructural
      techniques to assess synaptic numbers in these two regions of association cortex.
      Both cingulate areas demonstrated a significant loss in lamina III in AD, while
      only the posterior cingulate manifested a loss in lamina V. The failure to find a
      significant change in lamina V of the anterior cingulate may be related to its
      connectivity with the motor system. The heterogeneity of synaptic change in this
      cortical region may reflect important information concerning corticocortico
      connectivity changes in AD.

PMID- 12214037
TI  - Serum p97 levels as an aid to identifying Alzheimer's disease.
AB  - Background: The application of formal clinical diagnostic criteria for the
      identification of Alzheimer's Disease (AD) has improved diagnostic sensitivity.
      However, there remains a need for non-invasive biological markers and laboratory
      tests, which can facilitate case identification, and the assessment of treatment
      response. The p97 protein is a secreted protein specifically expressed by amyloid
      plaque associated reactive microglia that may have AD diagnostic ability.
      Methods: A quantitative radioimmunoassay was developed to measure serum p97. This
      study, under a double blind protocol, evaluated the utility of serum p97 as
      diagnostic test for AD. All subjects were referred to the UBC Clinic for
      Alzheimer's Disease and Related Disorders (CADRD) for clinical assessment of
      dementia. A serum p97 sample was obtained at the time of assessment but diagnosis
      of disease was determined independently of p97 examination. Results: "Possible"
      and "probable" AD cases (n = 41) and cognitively normal controls (n = 64) showed
      a highly significant difference in mean p97 concentration (41 vs. 20 ng/ml,
      p<0.001). There was some overlap in p97 distributions between AD cases and
      control subjects. The area under the curve (AUC) for the receiver operator curve
      (ROC) was 0.812. Conclusions: These results further support the specificity of
      high serum p97 levels in AD and its potential utility as a biological marker in
      AD. The reproducible elevation of serum p97 in AD underlines the need to further
      determine its role as a biological marker and diagnostic adjunct for AD.

PMID- 12214038
TI  - The role of kynurenines in the production of neuronal death, and the
      neuroprotective effect of purines.
AB  - The kynurenine metabolic pathway from tryptophan accounts for a large proportion
      of the metabolism of this amino acid in the brain. Although a major route for the
      generation of the essential co-factor nicotinamide adenine dinucleotide (NAD),
      two components of the pathway have marked effects on neurons. Quinolinic acid is
      an agonist at N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors, while
      kynurenic acid is an antagonist and, thus, a potential neuroprotectant. The
      levels of quinolinic acid are known to increase substantially following cerebral
      insults or infection, and has been most clearly implicated in the AIDS-dementia
      complex. The actions of quinolinic acid and NMDA show subtle differences,
      however, which suggest other factors contributing to cell damage. In this article
      we review the evidence that free radicals may be involved in the neurotoxic
      effects of quinolinic acid and consider the possibility that quinolinic acid
      might be involved in Alzheimer's disease. Finally, adenosine receptor ligands can
      modulate neuronal damage, supporting the view that they may represent suitable
      targets for the development of novel neuroprotectant drugs for the treatment of
      Alzheimer's and other neurodegenerative disorders.

PMID- 12214039
TI  - Olfaction in elderly and patients with Alzheimer's disease: Differing feedback
      conditions.
AB  - Objective: To determine the capability of patients with Alzheimer's disease (AD)
      and age-matched controls to discriminate and recognize odorants equilibrated for
      strength and familiarity, and to determine if immediate corrective-feedback can
      improve performance in either task. Major results: No significant differences
      between elderly controls (EC) and AD patients were apparent for the
      discrimination task regardless of feedback condition. The EC group outperformed
      the AD group on the recognition task. Feedback enhanced EC group performance but
      failed to benefit the AD group. Conclusions: Early in the disease process, AD
      subjects have a deficit in processing olfactory cues at levels beyond that
      necessary for discrimination. This deficit is specifically related to the
      olfactory system and is in addition to any general cognitive deficits they may
      have. Feedback is ineffective for AD subjects but can greatly enhance the
      performance of the intact elderly on tasks requiring the verbal mediation of
      olfactory cues.

PMID- 12214040
TI  - Hyperphosphorylation of the retinoblastoma gene product and altered subcellular
      distribution of E2F-1 during Alzheimer's disease and amyotrophic lateral
      sclerosis.
AB  - The molecular mechanisms that regulate neuronal cell death in neurodegenerative
      diseases remain unclear. During neurologic diseases numerous neuronal and glial
      intracellular signaling pathways are activated by changes within the
      extracellular environment, which culminate in alterations of nuclear proteins and
      gene expression. Among the proteins activated or expressed during
      neurodegenerative diseases include proteins that function during the cell cycle.
      Early events in cell cycle activation include transition from the G1 to S phase
      of the cell cycle, which is regulated by the activity of proteins from the
      retinoblastoma (pRb) and E2F gene families of transcriptional regulators.
      Hyperphosphorylation of pRb induces the activation of E2F proteins at the G1-to-S
      cell cycle transition. Using brain and spinal cord tissues from non-demented
      control, Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS)
      patients, we identified increased levels of hyperphosphorylated pRb in AD and ALS
      patients. In addition, we observed altered subcellular distribution of E2F-1
      during AD and ALS. Our results suggest that activation and re-distribution of
      early cell cycle transcriptional regulators occurs in both AD and ALS.

PMID- 12214041
TI  - Cyclosporin A inhibits Al-induced cytochrome c release from mitochondria in aged
      rabbits.
AB  - Neurodegenerative diseases including Alzheimer's disease are characterized by a
      progressive and selective neuronal loss via an apoptosis mechanism, and there is
      a growing body of evidence which supports a central role of mitochondria in this
      apoptotic cell death. Release of cytochrome c from the mitochondria to the
      cytosol is considered a critical step in apoptosis. Here we report that aluminum
      maltolate induces cytochrome c translocation into the cytosol as early as 3 hours
      in aged but not in young rabbit hippocampus. Pretreatment with cyclosporin A, an
      inhibitor of the mitochondria permeability transition pore (MTP), blocks
      cytochrome crelease. Therefore, it appears that aluminum maltolate-induced
      cytochrome c release results from opening of the MTP. This effect implicates
      aging as a prerequisite factor, since the MTP does not open in young animals.
      Mitochondrial injury thus may represent a primary initiator of neurodegeneration.

PMID- 12214042
TI  - Abetapp secretases are co-expressed with Abetapp in the pancreatic islets.
AB  - Amyloid beta protein precursor is cleaved by beta- and gamma-secretases to
      produce Abeta peptides which deposit in amyloid plaques in Alzheimer's disease
      (AD) brain. A recently identified beta-site cleaving enzyme (BACE) appears to
      fulfill the requirements for beta-secretase, and presenilin-1 (PS1) appears to
      constitute the catalytic component of gamma-secretase. Each protein has a close
      homologue (BACE2 and PS2, respectively), whose roles in AbetaPP cleavage remain
      uncertain. All four of these genes have been reported to be expressed in the
      human pancreas, but the cell types expressing these genes remains unknown. We
      demonstrate here the cell-specific expression of AbetaPP, BACE, BACE2, PS1, and
      PS2 in the human pancreas. The insulin-producing betacells were found to express
      AbetaPP, BACE and PS2 at high levels, and PS1 at a lower level. The other islet
      cell types expressed none of these five genes. By contrast, the exocrine ductal
      cells of the pancreas expressed AbetaPP and BACE2 selectively. These results
      suggest that secretase inhibitors under development for the treatment of AD,
      particularly those that target BACE, may have potential for adverse effects on
      pancreatic beta cell function, and therefore glycemic control.

PMID- 12214043
TI  - Amyloid beta protein precursor metabolism as a modulator of islet beta-cell
      function.

PMID- 12214044
TI  - Ginkgo biloba neuroprotection: Therapeutic implications in Alzheimer's disease.
AB  - An extract of Ginkgo biloba leaves, EGb761, is becoming one of the most popular
      dietary supplements in the United States to enhance memory. In Europe it is a
      commonly prescribed drug for treatment of age-related deterioration, including
      degenerative dementias of the Alzheimer type (AD). Substantial experimental
      evidence indicates that EGb761 has neuroprotective potency under conditions such
      as ischemia, seizures and peripheral nerve damage. However, the mechanisms of
      such neuroprotective effects remain unknown, partially because of the complex
      chemical composition of EGb761 and the resulting so-called "polyvalent" action.
      This review focuses on cellular and molecular approaches towards understanding
      the polyvalent action of EGb761 neuroprotective effect. Two potential mechanisms
      of action, reducing oxidative damage and stimulating cell survival machinery, are
      discussed. Better understanding of the neuroprotective mechanisms of EGb761 will
      provide impetus for possible combination therapies and for the design of
      rational, "mechanism-based" strategies that target age-related neurodegeneration
      and Alzheimer's disease.

PMID- 12214045
TI  - Ultrastructure evidence of necrotic neural cell death in familial Alzheimer's
      disease brains bearing presenilin-1 E280A mutation.
AB  - Recently, it has been demonstrated that there is no obvious correlation between
      DNA fragmentation (according to Terminal dUTP Nick-End Labeling technique) and
      the severity of amyloid-beta (Abeta) deposition and neurofibrillary tangle (NFT)
      formation in patients bearing mutations in presenilin 1[E280A]. Indeed, it was
      observed in 10 out of 48 brain sections TUNEL-positive labeling, while none
      showed classical apoptotic morphology. Based on these findings, we were
      interested to determine whether cortical cells from temporal and hippocampus post
      mortem brain sections die either by an apoptotic or necrotic process in FAD-brain
      sections labeled TUNEL positive compared with normal brain subjects labeled TUNEL
      negative using electron microscopy (EM). We found that FAD-brain sections labeled
      TUNEL positive display the typical morphological characteristics of cell death by
      necrosis i.e. the nuclear chromatin form flocculent aggregates with poorly
      defined edges and electron lucent (it does not appears black on EM); the
      chromatin aggregates are irregularly scattered through the nucleus; mitochondria
      are swoolen with flocculent matrix densities. No apoptotic bodies were observed
      in any of the brain areas studied. These results may indicate that necrosis is
      the most generalized cell death process occurring in terminal PS1E280A brains and
      the DNA fragmentation of nuclei labeled by TUNEL technique may reflect DNA
      vulnerability. Thus, cell death by necrosis and the accompanying
      histopathological observations such as severe deposition of amyloid plaques and
      NFTs, severe gliosis, cortical depopulation, influx of lymphocytes indicative of
      a chronic inflammation may have an important impact on future therapeutic
      strategies in the treatment of PS1E280A patients.

PMID- 12214046
TI  - Sequence of neurofibrillary changes in aging and Alzheimer's disease: A confocal
      study with phospho-tau antibody, AD2.
AB  - In the present study, neurons of the entorhinal cortex, hippocampus and frontal
      lobe from non-demented and Alzheimer's disease (AD) cases, were stained in order
      to study neurofibrillary changes. We have used double immunolabeling with a
      phosphorylation dependent monoclonal antibody (mAb) to tau, AD2, and the
      histochemical dye thiazin red (TR). MAb AD2 specifically recognizes
      phosphorylated Ser396 and Ser404, while TR shows binding sites for amyloid-beta$
      and tau when they are in fibrillar states. We show a morphological sequence of
      changes in the development of neurofibrillary tangles (NFTs), starting from mAb
      AD2 diffuse labeling in non-NFT bearing cells recognized by mAb AD2, then going
      through two subtypes of intracellular NFTs, to a final stage as extracellular
      NFTs. Morphometric analysis of the density of AD2 immunoreactive structures
      showed the NFT density in hippocampus and frontal lobe were the best parameters
      to differentiate normal aging from AD. Densities of AD2 immunoreactive structures
      in hippocampus and frontal lobe correlated with the Clinical Dementing Rating
      score. Based upon the variety of appearances of immunoreactivity displayed by mAb
      AD2, we were able to stage neurofibrillary changes at the level of individual
      neurons and brain areas. Our results demonstrate that the intensity of
      neurofibrillary changes in the hippocampus as well as the extent of the
      degeneration process in association areas differentiate normal aging from AD, and
      are well correlated with cognitive impairment.

PMID- 12214047
TI  - Biomarkers of Alzheimer's disease: Bridging the gap between basic science and
      clinical practice.

PMID- 12214048
TI  - The neuropsychological diagnosis of Alzheimer's disease.
AB  - Neuropsychological assessment potentially subserves several functions in subjects
      in whom Alzheimer's disease (AD) is suspected. Such assessment can detect the
      presence of brain disease once significant neuronal disruption has occurred.
      Analysis of the pattern and evolution of cognitive deficits allows inferences to
      be drawn regarding the likely underlying pathology. Neuropsychological assessment
      enables delineation of the particular cognitive strengths and weaknesses of
      individual patients, facilitating the construction of individual management
      programs. Lastly, cognitive testing provides a cost-effective means of monitoring
      disease progression and the effects of treatment. This review describes the
      typical pattern and evolution of cognitive deficits in AD, outlines a number of
      variant presentations, discusses the differential diagnosis from other dementias,
      and addresses the issue of progression to clinically probable AD in the
      cognitively impaired, non-demented elderly. It is anticipated that biomarkers for
      AD will complement neuropsychological assessment by enabling disease detection
      before unequivocal cognitive deterioration has ensued, and by improving the
      accuracy of clinical diagnosis of dementia type. The development of reliable
      biomarkers will also enable improvements in the sensitivity and accuracy of
      neuropsychological assessment in AD to be made, more quickly and efficiently than
      is currently possible using longitudinal studies.

PMID- 12214049
TI  - Incorporating biomarkers into clinical drug trials in Alzheimer's disease.
AB  - Incorporating biomarkers into clinical drug trials for Alzheimer's disease (AD)
      could 1) increase the homogeneity of patients through improved diagnosis, 2)
      establish surrogate outcome measures for drug efficacy, 3) test pharmacogenetic
      bases of drug response, and 4) verify proposed mechanisms of drug action. Among
      biological correlates of AD, those with the greatest potential to improve
      diagnostic accuracy are genetic abnormalities that cause AD or increase the risk
      of AD; characteristic changes in amyloid derivatives and tau and blood in CSF;
      and neuroimaging detection of brain atrophy and reduction in brain metabolism and
      blood flow. Although there are no AD biological markers that qualify as true
      surrogate endpoints in clinical drug trials, indices of brain atrophy show
      promise as a technique to track progression of dementia and as a measure of
      treatment efficacy. Anti-amyloid strategies for treatment are the leading
      candidates for the next generation of Alzheimer therapies. Predicted changes in
      amyloid derivative levels in CSF can help verify drug activity and illuminate the
      mechanism of action.

PMID- 12214050
TI  - Genetic markers in the diagnosis of Alzheimer's disease.
AB  - Abbreviations: AD, Alzheimer's disease; AbetaPP, amyloid beta protein precursor;
      BACE, beta-site AbetaPP cleaving enzyme; PS1, presenilin-1; PS2, presenilin-2;
      APOE, apolipoprotein E; LRP, low density lipoprotein receptor-related protein;
      SNPs, single-nucleotide polymorphisms; A2M, alpha-2-macroglobulin. Alzheimer's
      disease (AD) is the most common neurodegenerative disorder associated with
      dementia in the elderly population. Its clinical symptoms are manifest with
      increasing prominence during mid- to late stages of adulthood. In the absence of
      precise biological indicators that precede or accompany the cognitive decline,
      diagnostic confirmation of AD requires postmortem detection of histopathological
      characteristics such as amyloid plaques, neurofibrillary tangles, and extensive
      cortical atrophy. While the etiology of AD remains incompletely understood, it
      was recognized early on that the observed familial aggregation of AD implied the
      presence of one or more inherited susceptibility markers that could be useful in
      diagnosis and treatment. To date, genetic analyses of these pedigrees have
      resolved four independent genetic loci linked with inherited susceptibility to
      AD.

PMID- 12214051
TI  - Amyloid Abeta levels in Alzheimer's disease - A diagnostic tool and the key to
      understanding the natural history of Abeta?
AB  - The biogenesis and degradation/clearance of Abeta amyloid lies at the centre of
      the pathogenesis of Alzheimer's disease. Quantification of the various metabolic
      pools of Abeta in the brains and in the periphery may aid in diagnosis, prognosis
      and the elucidation of the natural history of this disorder. Estimation of the
      Abeta levels using immunoassays (ELISA and the western blots) are complementary
      techniques which are now being applied in humans and experimental models. The
      various forms of Abeta in differing cellular compartments are now being assayed,
      and a picture of the natural history of Alzheimer's disease is beginning to
      emerge.

PMID- 12214052
TI  - Cerebrospinal fluid Abeta40 and Abeta42: Natural course and clinical usefulness.
AB  - Amyloid beta protein 40 (Abeta40) and 42 (Abeta42), major components of senile
      plaque amyloids, are physiological peptides present in the brain, cerebrospinal
      fluid (CSF) and plasma. The levels of CSF Abeta40 and beta42(43) show a U-shaped
      natural course in normal aging. The increase of Abeta42(43) over 60 years of age
      is inhibited in Alzheimer's disease (AD). This specific alteration of CSF
      Abeta42(43) correlates with Abeta deposits in the AD brain providing a biological
      basis for a biomarker of AD. In the GTT2 study, assays of the CSF Abeta ratio
      [(Abeta40/ Abeta42(43)] showed a diagnostic sensitivity (59%) specificity (88%)
      The levels of the Abeta ratio increased from early to late stages of AD.
      Combination assays of CSF tau and Abeta ratio provided further efficient
      diagnostic sensitivity (81%) reliability of the assay may prompt worldwide usage
      of these CSF biomarkers for Alzheimer's patients.

PMID- 12214053
TI  - Acetylcholinesterase and butyrylcholinesterase glycoforms are biomarkers of
      Alzheimer's disease.
AB  - The identification of a biochemical marker in cerebrospinal fluid (CSF) that can
      discriminate between Alzheimer's disease (AD) and other dementia-causing diseases
      would be a major advance. Our previous studies have shown that the glycosylation
      of acetylcholinesterase (AChE) is altered in the post mortem brain and
      cerebrospinal fluid of AD patients. We have also found that the glycosylation of
      AChE is altered in lumbar CSF collected ante mortem. The change in glycosylation
      of AChE is very specific for AD and is not seen in many other neurological
      diseases including other dementias. The sensitivity of detection of AD using AChE
      glycosylation (60-80%) satisfactory diagnostic marker. However, more recently we
      have found that the glycosylation of the related enzyme butyrylcholinesterase
      (BuChE) is also altered in AD CSF. By combining the analysis of AChE
      glycosylation with that of BuChE glycosylation, improved sensitivity of detection
      is obtained. We propose that AChE and BuChE glycosylation may be of diagnostic
      value, especially when used in combination with other CSF markers such as Abeta
      or tau.

PMID- 12214054
TI  - Abnormalities in oxidative processes in non-neuronal tissues from patients with
      Alzheimer's disease.
AB  - Overwhelming evidence demonstrates that oxidative stress occurs in brains from
      patients with Alzheimer's Disease (AD). Whether the oxidative stress is secondary
      to neurodegeneration, or if it underlies the pathology is not clear. The
      persistence of AD-related abnormalities in oxidative processes in non-neuronal
      tissues, including cultured cells, infers that an imbalance in production and
      removal of reactive oxygen species is an inherent property of cells from AD
      patients. These results suggest that changes in oxidative processes in AD cells
      could precede and/or cause AD-related neuropathology. Abnormalities in oxidative
      processes may also cause changes in signal transduction systems such as calcium
      that occur in cells from AD patients. The ability to manipulate oxidative
      processes in peripheral tissues, especially cultured cells, from AD patients
      should facilitate a mechanistic understanding of the changes in oxidative
      processes in AD brain. The use of peripheral tissues has the potential to
      identify both state and trait dependent diagnostic markers, which could be used
      as endpoints for selecting treatments or monitoring therapeutic effectiveness.

PMID- 12214055
TI  - Assessing p97 as an Alzheimer's disease serum biomarker.
AB  - The search is ongoing for a reliable serum biomarker for AD. The level of iron is
      elevated in the brain of Alzheimer's disease (AD) patients. Our studies have
      demonstrated that the level of the iron transport protein, p97, is increased in
      the serum of AD patients but not in various control groups. These results have
      recently been confirmed by another laboratory who extended our findings by
      demonstrating that p97 is not elevated in other neurodegenerative diseases. This
      qualifies p97 as a potentially powerful biomarker for AD. Although the
      relationship between increased level of iron and p97 in the AD brain is not well
      understood, our research supports the hypothesis that p97 over-expressed by
      senile plaque associated reactive microglia is exocytosed and appears in blood.
      The relationship between elevated levels of serum p97 and AD, together with the
      possible future clinical application of p97 are considered in this report.

PMID- 12214056
TI  - The AD7c-NTP neuronal thread protein biomarker for detecting Alzheimer's disease.
AB  - Dementia in Alzheimer's disease (AD) is ultimately due to cell loss mediated by
      several mechanisms including, apoptosis, impaired mitochondrial function, and
      possibly necrosis. A second major neuroanatomic correlate of dementia is aberrant
      cortical neuritic sprouting with abundant proliferation of dystrophic neurites.
      Early in vivo detection of AD will require non-invasive assays of highly
      sensitive and relatively specific biomarkers that reflect these fundamental
      abnormalities in cellular function. The AD-associated neuronal thread protein
      (AD7c-NTP) gene encodes a approximately 41 kD membrane-spanning phosphoprotein
      that causes apoptosis and neuritic sprouting in transfected neuronal cells. The
      AD7c-NTP gene is over-expressed in AD beginning early in the course of disease.
      In the brain, increased AD7c-NTP immunoreactivity is associated with phospho-tau
      immunoreactive cytoskeletal lesions, but not with amyloid-beta accumulations. The
      levels of AD7c-NTP in postmortem brain tissue correlate with the levels measured
      in paired ventricular fluid samples, suggesting that the protein is secreted or
      released by dying cells into cerebrospinal fluid (CSF). In this regard, elevated
      levels of AD7c-NTP can be detected in both CSF and urine of patients with early
      or moderately severe AD, and the CSF and urinary levels of AD7c-NTP correlate
      with the severity of dementia. The newest configuration of the AD7c-NTP assay,
      termed "7c Gold", has greater than 90% aggregate results from a number of studies
      suggest that AD7c-NTP is an excellent biomarker that could be helpful in the
      routine clinical evaluation of elderly patients at risk for AD.

PMID- 12214057
TI  - The number of neurons in the inferior olivary nucleus in Alzheimer's disease and
      normal aging: A stereological study using the optical fractionator.
AB  - The nuclei of the olivary complex are involved in regulating motor movements and
      in motor learning. Aging is characterized by a progressive accumulation of
      lipofuscin while the number of olivary neurons is unchanged. It is not known
      whether neuronal loss occurs in the olivary nucleus during Alzheimer's disease
      (AD). The aim of this study was to estimate the total number of neurons in the
      principal olivary nucleus (PO) in AD and control brains using an optimized design
      for sampling and an unbiased stereological method called the optical
      fractionator. This study was based on 13 control (mean age =57 y, range 17-95 y)
      and 16 AD brains (mean age = 86 y, range 67-93 y). Using paraffin-embedded, Nissl
      stained sections for quantification, we found a significant difference between
      the mean values (mean+/-SD) of the AD group vs. aged-matched controls (4.3x10^5+/
      1.1 vs. 6.53x10^5+/-1.39 p<0,003). There was no significant difference between
      younger controls vs. older controls (7.1x10^5+/-1.5 vs. 6.5x10^5+/-1.4 p=0.76).
      While there was no neuronal loss in normal aging, in AD the PO is characterized
      by a significant neuronal loss up to 34%. can occur in regions devoid of
      neurofibrillary changes.

PMID- 12214058
TI  - Isolation of human neuronal cells resistant to toxicity by the prion protein
      peptide 106-126.
AB  - Prion diseases or transmissible spongiform encephalopathies, are
      neurodegenerative disorders that are genetic, sporadic, or infectious. The
      pathogenetic event common to all prion disorders is the conformational
      transformation of the cellular prion protein (PrP^C) to the scrapie form
      (PrP^Sc), that deposits in the brain parenchyma and induces neuronal death.
      Infectious prion disorders are caused by exogenously introduced PrP^Sc that acts
      as a template in the conversion of endogenous PrP^C to nascent PrP^Sc, and
      subsequently the process becomes autocatalytic. To understand the process of
      cellular uptake of PrP^Sc and its mechanism of cellular toxicity, previous
      studies have used a PrP fragment spanning residues 106-126 (PrP^Tx) that is toxic
      to primary neurons in culture, and mimics PrP^Sc in its biophysical properties
      [9,11,14]. Several possible mechanisms of cell death by PrP^Tx have been proposed
      [2,3,10,11,18], but the existing data are unclear. To identify the biochemical
      pathways of neurotoxicity by this fragment, we have isolated mutant neuroblastoma
      and NT-2 cells that are resistant to toxicity by PrP^Tx. We show that these cells
      bind and internalize PrP^Tx in a temperature dependent fashion, and the peptide
      accumulates in intracellular compartments, probably lysosomes, where it has an
      unusually long half-life. The PrP^Tx-resistant phenotype of the cells reported in
      this study could result from aberrant binding or internalization of the peptide,
      or due to an abnormality in the downstream pathway(s) of neuronal toxicity. The
      PrP^Tx-resistant cells are therefore a useful tool for evaluating the cellular
      and biochemical pathways that lead to cell death by this peptide, and will
      provide insight into the mechanism(s) of neurotoxicity by PrP^Sc.

PMID- 12214059
TI  - PAMP and PARL, two novel putative metalloproteases interacting with the COOH
      terminus of Presenilin-1 and -2.
AB  - The familial Alzheimer's disease gene products, presenilin-1 and presenilin-2
      (PS1 and PS2), are involved in amyloid beta-protein precursor processing
      (AbetaPP), Notch receptor signaling, and programmed cell death. However, the
      molecular mechanisms by which presenilins regulate these processes remain
      unknown. Clues about the function of a protein can be obtained by seeing whether
      it interacts with another protein of known function. Using the yeast two-hybrid
      system, we identified two proteins that interact and colocalize with the
      presenilins. One of these newly detected presenilin-interacting proteins belongs
      to the FtsH family of ATP-dependent proteases, and the other one belongs to
      Rhomboid superfamily of membrane proteins that are highly conserved in
      eukaryotes, archaea and bacteria. Based on the pattern of amino acid residues
      conservation in the Rhomboid superfamily, we hypothesize that these proteins
      possess a metal-dependent enzymatic, possibly protease activity. The two putative
      proteases interacting with presenilins could mediate specific proteolysis of
      membrane proteins and contribute to the network of interactions in which
      presenilins are involved.

PMID- 12214060
TI  - Peering into proteolysis with presenilins.
AB  - Presenilins were originally identified because they cause a neurodegenerative
      disease, but the impact of these proteins on the neuron appears to extend beyond
      neurodegeneration and into fundamental concepts of cell biology and development.
      Presenilins were identified as a result of the steady march of molecular genetics
      which first lead to identification of loci on chromosomes 1 and 14 that
      segregated with the phenotype of early onset familial Alzheimer Disease (AD), and
      then to discovery of the genes coding for PS1 and PS2.

PMID- 12214061
TI  - Constitutive Wee1 activity in adult brain neurons with M phase-type alterations
      in Alzheimer neurodegeneration.
AB  - The cdc2/cyclin B1 kinase is absent from neurons that are terminally
      differentiated. However, unscheduled activation of Cdc2/cyclin B and accumulation
      of mitotic phosphoepitopes have been described in degenerating neurons of
      Alzheimer's disease (AD), and their appearance precedes hallmark lesion
      formation. In cycling cells the timing of cdc2 activation and onset of mitosis
      are determined by the Wee1 tyrosine kinase. We therefore investigated the Wee1
      kinase in human brain. Surprisingly, we have found that the enzyme is
      constitutively active in neurons of normal brain. Consistent with its behavior in
      M phase, Wee1 in AD has decreased activity, becomes MPM-2 immunoreactive, and is
      redistributed from its normally nuclear domain to the cytoplasm of affected
      neurons. These data suggest that Wee1 functions in normal postmitotic neurons,
      but is altered in AD so as to promote activation of Cdc2/cyclin B1. Thus, Wee1 is
      yet another mitotic regulator that participates in the AD neurodegenerative
      process.

PMID- 12214062
TI  - The severity of cortical Alzheimer's type changes is positively correlated with
      increased amyloid-beta Levels: Resolubilization of amyloid-beta with transition
      metal ion chelators.
AB  - The most consistent diagnostic neuropathological lesion in Alzheimer's disease
      (AD) is the senile plaque of which the 4 kD amyloid-beta (Abeta) peptide is the
      major proteinaceous component. In this study cortical Abeta levels were
      immunochemically measured in 70 post-mortem human brains and compared against
      their neuropathological grading as determined by the densities of amyloid plaques
      and neurofibrillary tangles. The mean concentration of cortical Abeta/mg protein
      increased with the severity of the cortical degenerative changes (AD0 < AD1 < AD2
      < AD3). Brains with the severe degenerative changes (AD3), corresponded to
      definite AD cases and exhibited significantly increased concentrations of Abeta
      (11.1+/-3.08 ng/mg total protein, n=17) when compared with control brains without
      any degenerative changes (AD0; 0.06+/-0.06 ng/mg total protein, n=14,P=0.003).
      The extraction of Abeta from the cortex of AD3 brains was significantly enhanced
      in a dose dependent manner by the presence of the metal ion chelator N,N,N',N'
      tetrakis(2-pyridylmethyl) ethylenediamine (5 mM TPEN, P < 0.0001). The
      chelator/antioxidant 1,2-dithiolane-3-pentanoic acid (lipoic acid), also
      resolubilized Abetain a dose-dependant manner. Both chelators also enhanced the
      extraction of Abeta from the frontal cortex of AbetaPP-transgenic mice suggesting
      this animal model of amyloidosis may be useful for evaluating the biochemical and
      therapeutic effects of chelators/antioxidants on Abeta deposition. In summary our
      results indicate that increased Abeta load is correlated with the severity of the
      cortical AD-type changes and that chelators/antioxidants may be useful in
      reducing neuronal amyloid burden.

PMID- 12214063
TI  - Cholesterol depletion with physiological concentrations of a statin decreases the
      formation of the Alzheimer amyloid Abeta peptide.
AB  - Epidemiological studies have demonstrated that hypercholsterolemia is a
      significant risk factor for Alzheimer's disease (AD). The mechanism by which
      increased cholesterol may contribute to AD is unknown. However, as the generation
      and accumulation of the amyloid Abeta peptide in the brain appears to be
      significant for the initiation and progression of AD, it is possible that
      cholesterol levels can regulate Abeta formation and/or clearance. To test the
      effects of altering cholesterol on Abeta formation, we incubated cells in the
      presence of lipid depleted serum, with or without the active metabolite of the
      HMG-CoA reductase inhibitor lovastatin. After confirming that cholesterol was
      depleted in the cells, we then measured the fraction of Abeta formed from its
      precursor betaPP under each condition. We observed that cholesterol depletion led
      to a profound decrease in the levels of Abeta released from the cells. This
      effect of lovastatin acid was observed at concentrations of 0.05-5 &mgr;M, ranges
      where this compound is effective at inhibiting HMG-CoA reductase, thereby
      inhibiting cholesterol synthesis. In contrast, the release of an additional
      AbetaPP fragment, AbetaPPs, was only modestly reduced by cholesterol treatment.
      In further studies, we determined that the decreased release of Abeta was not due
      to its accumulation in the cell, but rather due to decreased formation of Abeta.
      Finally, we were able to exclude decreased maturation (glycosylation and
      sulfation) of newly synthesized AbetaPP as a cause for the effects of lovastatin
      acid on betaPP processing and Abeta formation. Our results demonstrate that
      reducing cellular cholesterol by the use of an HMG-CoA reductase inhibitor
      regulates Abeta formation. This effect may involve alterations in the trafficking
      of AbetaPP and/or alterations in the activity of the proteases that cleave
      AbetaPP. The results suggest a mechanism by which hypercholesterolemia may
      increase risk for AD and indicate that reduction in cholesterol may delay the
      onset and/or slow the progression of AD.

PMID- 12214064
TI  - Apoptotic neurons in Alzheimer's disease frequently show intracellular Abeta42
      labeling.
AB  - It is widely accepted that Abeta plays a pivotal role in the pathogenesis of
      Alzheimer's disease (AD) [27]. Attention has been focused mainly on how
      extracellular Abeta exerts its effects on neuronal cells [7,11,16,32]. However,
      neuronal degeneration from an accumulation of intracellular Abetax-42 (iAbeta42)
      occurs in presenilin 1 (PS1) mutant mice without extracellular Abeta deposits
      [5]. In the present study, intracellular deposits of iAbeta42 are correlated with
      apoptotic cell death in AD and PS-1 familial AD (PS1 FAD) brains by means of
      triple staining with antibodies to Abeta, TUNEL, and staining with Hoechst 33342.
      Neurons simultaneously positive for iAbeta42 and the TUNEL assay were
      significantly more abundant in AD brains than in controls. The number of
      apoptotic neurons with intracellular neurofibrillary tangles (iNFTs) was
      insignificant. Our results indicate that intraneuronal deposition of a neurotoxic
      form of Abeta seems to be an early event in the neurodegeneration of AD.

PMID- 12214065
TI  - Commentary: Abeta N- Terminal Isoforms: Critical contributors in the course of AD
      pathophysiology.
AB  - The assessment of protein or amino acid variations across evolution allows one to
      glean divergent features of disease-specific pathology. Within the Alzheimer's
      disease (AD) literature, extensive differences in Abeta processing across cell
      lines and evolution have clearly been observed. In the recent past, increased
      levels of amyloid beta Abeta1-42 have been heralded to be what distinguishes
      whether one is prone to the development of AD [59]. However, observations in
      naturally occurring, non-transgenic animals which display a great deal of
      parenchymal Abeta1-42 (Abeta found within extracellular plaque deposits) and a
      complete lack ofbeta1-40 within these same Abeta1-42 plaques raise the issue of
      whether Abetax-42 (Abeta that is truncated or modified at the N- terminus),
      rather than Abeta1-42, is instead the critical mediator of Abeta production and
      pathogenesis [47,49]. Distinct ratios of Abeta N-terminal variants (i.e. Abeta1
      x, Abeta3-x, Abeta11-x, beta17-x) have been assessed in human amyloid plaques
      [18,21,40,41,42,47,48,49,52]. Moreover, ratios of specific Abeta N-terminal
      variants separate naturally occurring, non-transgenic animals which develop
      abundant levels of Abetax-42 and not Abetax-40 from human AD participants who
      harbor plaques that contain both the Abetax-42 and Abetax-40 variants [49]. Next,
      Teller and colleagues have demonstrated the presence of N-terminal truncated
      soluble 3kD (likely Abeta17-x) and 3.7kD peptides (in addition to 4kD Abeta) well
      before the appearance of amyloid plaques in Down Syndrome brain [51], indicating
      an early contribution of thebeta N-terminus to the formation of amyloid
      pathology. Additional critical facts concerning the major contribution of the
      Abeta N-terminus in AD pathogenesis include observations which support thatbeta
      generated by rodent neurons is predominantly truncated at Abeta11-x [13], the
      major form of APP C-terminal fragments in mice lacking functional PS1 is
      AbetaPP11-98 [9], beta11-x expression is increased as a function of BACE
      expression [55], and an interrelationship between presenilin-1 mutations and
      increased levels of N-terminally truncatedbeta [40]. This commentary highlights
      current understanding and potential biochemical, pathological, and cell
      biological contributions of Abeta N-terminal variants implicated during the
      course of AD pathogenesis. Although the amyloid beta protein precursor (AbetaPP)
      gene and Abeta are highly conserved across mammalian species, there are species
      specific differences. For instance, the primate, guinea pig, canine, and polar
      bear share an identical Abeta sequence to that observed in human brain while the
      rat displays a distinct amino acid sequence with substitutions at residues 5
      (Arg), 10 (Tyr), and 13 (His) [24,37]. All of these mammals generate Abeta1-42
      via cleavage by at least two enzymes, beta (beta-) secretase and gamma (gamma-)
      secretase (Fig. 1). The enzyme that liberates the N- terminus of the Abeta
      peptide ('beta-secretase') is also termed BACE (beta-site AbetaPP cleaving
      enzyme) [55]. Cathepsin D, which accumulates within AD neurons [15], also cleaves
      at the N-terminal side of the first aspartate residue of amyloid beta [2].beta
      secretase activity is necessary in order to initiate 4kD beta1-x formation by
      cleaving AbetaPP at the N-terminus and results in the release of a soluble 100kD
      AbetaPP N- terminal fragment and a 12kD membrane bound C-terminal fragment
      (C99/C100) [55]. The carboxyl-terminus of the Abetapeptide is liberated through
      cleavage by the enzyme termed gamma-secretase. In the past, potential AD
      therapeutic strategies have mainly been geared towards gamma-secretase
      inhibition. However, such strategies alone no longer appear sound as it is clear
      that the AbetaPP C99/C100 fragment itself, which requires beta-, but not gamma-,
      secretase cleavage for generation and includes the entire Abeta peptide, is
      neurotoxic when evaluated in cultured cells [12,30,34]. Thus, gamma-secretase
      inhibition alone would not preclude the generation of the neurotoxic C99/C100
      fragment.

PMID- 12214066
TI  - Alzheimer's disease centers and the dementias of aging program of the national
      institute on aging: a brief overview.
AB  - The National Institute on Aging (NIA) of the National Institutes of Health (NIH)
      has stimulated many recent landmark advances in the understanding and treatment
      of Alzheimer's disease (AD) and related dementing disorders. This progress is due
      in part to an extramural network of AD Centers (ADCs) that was established 15
      years ago as a component of the NIA Dementias of Aging Program. The ADCs provide
      a unique infrastructure to support and augment studies on the pathobiology of AD
      and related disorders as well as to educate scientists and the public about these
      neurodegenerative dementias. The mission and structure of the ADC network are
      summarized to illustrate how the ADCs play important roles in accelerating
      development of effective therapies for AD and related disorders.

PMID- 12214067
TI  - Henry M. Wisniewski - fond memories.

PMID- 12214068
TI  - Henry M. Wisniewski M.D. Ph.D.

PMID- 12214069
TI  - Amyloid beta40/42 clearance across the blood-brain barrier following intra
      ventricular injections in wild-type, apoE knock-out and human apoE3 or E4
      expressing transgenic mice.
AB  - An important event in the pathogenesis of Alzheimer's disease (AD) is the
      deposition of the amyloid beta (Abeta)1-40 and 1-42 peptides in a fibrillar form,
      with Abeta42 typically having a greater propensity to undergo this conformational
      change. A major risk factor for late-onset AD is the inheritance of the
      apolipoprotein E (apoE) 4 allele [3,14,31]. We previously proposed that apoE may
      function as a "pathological chaperone" in the pathogenesis of AD (i.e. modulate
      the structure of Abeta, promoting or stabilizing a beta-sheet conformation),
      prior to the discovery of this linkage [7,40,41,42]. Data from apoE knockout /
      AbetaPP^(V717F) mice, has shown that the presence of apoE is necessary for
      cerebral amyloid formation [1,2], consistent with our hypothesis. However, in
      betaPP^(V717F) mice expressing human apoE3 or E4 early Abeta deposition at 9
      months is suppressed, but by 15 months both human apoE expressing mice had
      significant fibrillar Abeta deposits with the apoE4 expressing mice having a 10
      fold greater amyloid burden [8,9]. This and other data has suggested that apoE,
      in addition to having a facilitating role in fibril formation, may also influence
      clearance of Abeta peptides. In order to address if apoE affects the clearance of
      Abeta peptides across the blood-brain barrier (BBB) and whether there are
      differences in the clearance of Abeta40 versus Abeta42, we performed
      stereotactic, intra-ventricular micro-injections of Abeta40, Abeta42 or control
      peptides in wild-type, apoE knock-out (KO) or human apoE3 or apoE4 expressing
      transgenic mice. We found that consistent with other studies [5], Abeta40 is
      rapidly cleared from the brain across the BBB; however, Abeta42 is cleared much
      less effectively. This clearance of exogenous Abeta peptides across the BBB does
      not appear to be affected by apoE expression. This data suggests that Abeta42
      production may favor amyloid deposition due to a reduced clearance across the
      BBB, compared to Abeta40. In addition, our experiments support a role of apoE as
      a pathological chaperone, and do not suggest an isotype specific role of apoE in
      exogenous Abeta peptide clearance from the CSF across the BBB.

PMID- 12214070
TI  - Problems of cell death in neurodegeneration and Alzheimer's Disease.
AB  - Progressive cell loss in specific neuronal populations is a pathological hallmark
      of neurodegenerative diseases, but its mechanisms remain unresolved. Apoptosis or
      alternative pathways of neuronal death have been discussed in Alzheimer disease
      (AD) and other disorders. However, DNA fragmentation in human brain as a sign of
      neuronal injury is too frequent to account for the continuous loss in these
      slowly progressive diseases. In autopsy cases of AD, Parkinson's disease (PD),
      related disorders, and age-matched controls, DNA fragmentation using the TUNEL
      method and an array of apoptosis-related proteins (ARP), proto-oncogenes, and
      activated caspase 3, the key enzyme of late-stage apoptosis, were examined. In
      AD, a considerable number of hippocampal neurons and glial cells showed DNA
      fragmentation with a 3- to 6-fold increase related to amyloid deposits and
      neurofibrillary tangles, but only one in 2.600 to 5.650 neurons displayed
      apoptotic morphology and cytoplasmic immunoreactivity for activated caspase~3,
      whereas no neurons were labeled in age-matched controls. Caspase~3
      immunoreactivity was seen in granules of cells with granulovacuolar degeneration,
      in around 25% In progressive supranuclear palsy, only single neurons but
      oligodendrocytes in brainstem, around 25% TUNEL-positive and expressed both ARPs
      and activated caspase 3. In PD, dementia with Lewy bodies, and multisystem
      atrophy (MSA), TUNEL-positivity and expression of ARPs or activated caspase~3
      were only seen in microglia and oligodendrocytes with cytoplasmic inclusions in
      MSA, but not in neurons. These data provide evidence for extremely rare apoptotic
      neuronal death in AD and PSP compatible with the progression of neuronal
      degeneration in these chronic diseases. Apoptosis mainly involves reactive
      microglia and oligodendroglia, the latter occasionally involved by deposits of
      insoluble fibrillary proteins, while alternative mechanisms of neuronal death may
      occur. Susceptible cell populations in a proapoptotic environment, particularly
      in AD, show increased vulnerability towards metabolic or other noxious factors,
      with autophagy as a possible protective mechanism in early stages of programmed
      cell death. The intracellular cascade leading to cell death still awaits
      elucidation.

PMID- 12214071
TI  - Localization of active forms of C-jun kinase (JNK) and p38 kinase in Alzheimer's
      disease brains at different stages of neurofibrillary degeneration.
AB  - The principal protein component of paired helical filaments (PHFs) in Alzheimer
      disease is abnormally hyperphosphorylated tau (PHF-tau). The stress activated
      protein kinases JNK and p38 have been shown to phosphorylate tau at some sites
      only seen in PHF-tau. If JNK and p38 are involved in the abnormal
      hyperphosphorylation of tau, they should be activated in neurons undergoing
      neurofibrillary degeneration. In the present study, we determined the
      intracellular and regional distribution of the active forms of JNK and p38 kinase
      in entorhinal, hippocampal, and temporal cortices of brains staged for
      neurofibrillary changes according to Braak and Braak. Neurons with tangle-like
      inclusions positive for active forms of JNK and p38 kinase were found to appear
      first in the Pre-alpha layer of the entorhinal cortex, and then extend into other
      brain regions co-incident with the progressive sequence of neurofibrillary
      changes. The intraneuronal accumulation of active forms of JNK and p38 kinase
      apeared to precede the deposition of amyloid in the extracellular space. These
      data indicate that increased activation of the stress related kinases JNK and p38
      occurs very early in the disease and might be involved in the intraneuronal
      protein phosphorylation/dephosphorylation imbalance that leads to neurofibrillary
      degeneration in Alzheimer disease.

PMID- 12214072
TI  - Shift from fibrillar to nonfibrillar Abeta deposits in the neocortex of subjects
      with Alzheimer disease.
AB  - A morphometric study of amyloid-beta-positive plaques in the neocortex of eight
      non-demented people from 68 to 82 years of age and 17 subjects with late-stage
      Alzheimer disease (GDS stage 7/FAST stages 7a-f) from 73 to 93 years of age shows
      a shift from prevalence of fibrillar plaques to prevalence of nonfibrillar
      plaques. In the aged, non-demented subjects, about 4/mm^2 plaques are detectable
      in the neocortex, and the majority are fibrillar plaques. Specifically, 64% found
      to be classical fibrillar and Thioflavin-S-positive bright primitive plaques. A
      lower percentage of pale primitive plaques (35%) relatively small proportion of
      plaques that are poor in thioflavin S-positive fibrils. The numerical density of
      plaques in the severe stage of AD increases to about 41/mm^2. Severely demented
      subjects appear to maintain an active process of fibrillar plaque formation. This
      is reflected in the presence of 3% bright primitive plaques. Severely demented
      subjects also manifest plaque degradation, reflected in the presence of 22% and
      48% percentages of classical fibrillar plaques in non-demented subjects and in
      the end stage of disease suggest that once activated, the process of fibrillar
      plaque formation persists at a somewhat stable rate during the whole course of
      brain amyloidosis.

PMID- 12214073
TI  - From counting neurons to the preclinical diagnosis of Alzheimer's disease.
AB  - This article is a review of scientific work on Alzheimer neurofibrillary
      degeneration and Ass-amyloidosis that was done in collaboration with Dr. Henryk
      Wisniewski, in part at the Institute for Basic Research in Developmental
      Disabilities. Our work on paired helical filaments and the tau protein spans from
      basic immunocytochemical analyses of brain tissue to clinical application as a
      biological marker used in diagnostic tests. Even though only a small part of Dr.
      Wisniewski's scientific oeuvre, these data illustrate how a great scientist opens
      the field to his student, collaborator and friend, how basic science can evolve,
      and how results can be applied in clinical practice to the benefit of our
      patients.

PMID- 12214074
TI  - Cerebral amyloidosis, amyloid angiopathy, and their relationship to stroke and
      dementia.
AB  - Cerebral amyloid angiopathy (CAA) is the common term used to define the
      deposition of amyloid in the walls of medium- and small-size leptomeningeal and
      cortical arteries, arterioles and, less frequently, capillaries and veins. CAA is
      an important cause of cerebral hemorrhages although it may also lead to ischemic
      infarction and dementia. It is a feature commonly associated with normal aging,
      Alzheimer disease (AD), Down syndrome (DS), and Sporadic Cerebral Amyloid
      Angiopathy. Familial conditions in which amyloid is chiefly deposited as CAA
      include hereditary cerebral hemorrhage with amyloidosis of Icelandic type (HCHWA
      I), familial CAA related to Abeta variants, including hereditary cerebral
      hemorrhage with amyloidosis of Dutch origin (HCHWA-D), the transthyretin-related
      meningocerebrovascular amyloidosis of Hungarian and Ohio kindreds, the gelsolin
      related spinal and cerebral amyloid angiopathy, familial PrP-CAA, and the
      recently described chromosome 13 familial dementia in British and Danish
      kindreds. This review focuses on the various molecules and genetic variants that
      target the cerebral vessel walls producing clinical features related to stroke
      and/or dementia, and discusses the potential role of amyloid in the mechanism of
      neurodegeneration.

PMID- 12214075
TI  - Alzheimer's disease results from the cerebral accumulation and cytotoxicity of
      amyloid beta-protein.

PMID- 12214076
TI  - Henryk M. Wisniewski and the amyloid theory of Alzheimer's disease.

PMID- 12214077
TI  - Mechanisms of phenotypic heterogeneity in prion, Alzheimer and other
      conformational diseases.

PMID- 12214078
TI  - The neuronal endosomal-lysosomal system in Alzheimer's disease.
AB  - Robust activation of the neuronal lysosomal system and cellular pathways
      converging on the lysosome, such as the endocytic and autophagic pathways, are
      prominent neuropathological features of Alzheimer's disease. Disturbances of the
      neuronal endocytic pathway, which are one of the earliest known intracellular
      changes occurring in Alzheimer's disease and Down syndrome, provide insight into
      how beta-amyloidogenesis might be promoted in sporadic Alzheimer's disease, the
      most prevalent and least well understood form of the disease. Primary lysosomal
      system dysfunction in inherited disorders is commonly associated with prominent
      neurological phenotypes and neurodegeneration. New studies now directly implicate
      lysosomal cathepsins as proteases capable of initiating, as well as executing,
      cell death programs. These and other studies support the view that the
      progressive alterations of lysosomal system function in Alzheimer's disease have
      broad relevance to the neurodegenerative processes occurring during the disease.

PMID- 12214079
TI  - The genetic causes of neurodegenerative diseases.
AB  - With the application of molecular genetics, we are now beginning to understand
      the etiology and the early stages of pathogenesis of the major neurodegenerative
      diseases, including Alzheimer's disease, Parkinson's disease, Pick's disease and
      Progressive Supranuclear Palsy. Surprisingly, these studies are showing that
      these diseases share pathogenic mechanisms which involve tau or synuclein
      aggregation. In this article, I review the progress in the molecular genetic
      analysis of these major neurodegenerative diseases and discuss how they are
      related to each other.

PMID- 12214080
TI  - Brain degeneration linked to "fatal attractions" of proteins in Alzheimer's
      disease and related disorders.

PMID- 12214082
TI  - Molecular and cellular mediators of Alzheimer's disease inflammation.

PMID- 12214081
TI  - Recent advances in the understanding of the role of synaptic proteins in
      Alzheimer's Disease and other neurodegenerative disorders.
AB  - Synaptic damage is an early pathological event common to many neurodegenerative
      disorders such as Alzheimer's disease (AD) and is the best correlate to the
      cognitive impairment. Several molecules involved in AD and in other
      neurodegenerative disorders play an important role in synaptic function and when
      misfolded aggregate and form amyloid fibrils. Synaptic proteins with an amyloid
      domain include amyloid beta-protein precursor, prion protein, huntingtin, ataxin
      1 and alpha-synuclein. Two of the possible mechanisms by which alterations in
      synaptic proteins lead to synapse damage are: 1) misfolded or aggregated synaptic
      molecules have lost their normal function and/or 2) they have gained a toxic
      capacity. Recent studies support the possibility that while oligomers are toxic,
      polymers might be inactive. The mechanisms by which oligomers trigger synapse
      loss could be related to their ability to triggers stress signals once they enter
      the nucleus and/or accumulate at the endoplasmic reticulum.

PMID- 12214083
TI  - Response of the hypothalamic-pituitary-adrenal axis to lumbar puncture induced
      stress.
AB  - To assess lumbar puncture (LP) stress as measured by Hypothalamic-Pituitary
      Adrenal axis response, serum cortisols were measured before and after LP in
      Alzheimer's disease (AD) and healthy elderly individuals. There were no
      differences in baseline serum cortisol. AD group had significantly higher
      cortisols at 165 minutes post-LP. Growth curve analysis confirmed these findings
      and showed significant differences in cortisol levels overall. The AD males had
      higher cortisols at 105 minutes post-LP, but no other consistent gender
      differences emerged. The findings are consistent with the relative reduction in
      HPA negative feedback seen in AD. Overall, LP induces little change in group mean
      cortisol levels relative to inter-individual variation, indicating that while LP
      is an interesting model of neuroendocrine challenge, it needs to be tested in
      larger populations.

PMID- 12214084
TI  - Cerebrospinal fluid markers for Alzheimer's disease evaluated after acute
      ischemic stroke.
AB  - Potential cerebrospinal fluid (CSF) markers for Alzheimer's disease (AD) include
      tau protein, the 42 amino-acid form of amyloid beta (amyloid beta(1-42)) and
      apolipoprotein E (apoE). To study new aspects of these protein markers, we
      examined consecutive CSF samples from 26 patients with acute ischemic stroke. CSF
      samples were taken on day 0-1, day 2-3, day 7-9, 3 weeks and 3-5 months after the
      stroke. CSF-tau showed a marked increase day 2-3, which peaked after 1 week and
      returned to normal after 3-5 months. CSF-tau also showed correlation (r=0.95;
      p<0.01) with the size of the infarct. In contrast, CSF-amyloid beta(1-42) and CSF
      apoE showed no significant changes during the period. The marked increase in CSF
      tau levels after acute ischemic stroke indicate that CSF-tau reflect the degree
      of neuronal damage. The reason for unchanged levels of CSF-amyloid beta(1-42) and
      CSF-apoE after ischemic stroke remains unclear.

PMID- 12214085
TI  - Abeta immunoreactive material is present in several intracellular compartments in
      transfected, neuronally differentiated, P19 cells expressing the human amyloid
      beta-protein precursor.
AB  - Processing of the amyloid beta-protein precursor is believed to play a critical
      role in the development of Alzheimer's disease neuropathology. The localization
      of the human Abeta epitope within mature neuroectodermally differentiated
      embryonal carcinoma (P19) cells, stably transfected with the cDNA coding for a
      wild form human amyloid beta-protein precursor (AbetaPP 751) was investigated.
      For this, we applied high resolution electron microscopy and immunocytochemistry
      with a newly developed, highly specfic monoclonal antibody (McSA1). We observed
      immunoreactive signals in a number of subcellular organelles such as early
      endosomes, the trans-Golgi network and in the dilated rough endoplasmic
      reticulum, but not in lysosomes. Occasionally Abeta immunoreactivity was
      associated with microtubules and filaments, with the outer mitochondrial
      membrane, and with the nuclear envelope. These observations expand on current
      data regarding intracellular trafficking of AbetaPP fragments and provoke further
      questions regarding the role of intracellular Abeta peptides in basal conditions
      and pathological states.

PMID- 12214086
TI  - Correlation between Apolipoprotein-E polymorphism and Alzheimer's disease
      pathology.
AB  - Alzheimer's disease (AD) and small vessel disease dementia (SVDD) are common
      causes of dementia. The ApoE genotype has been proposed as a risk factor for AD.
      The frequency of the three ApoE alleles was correlated with the neuropathological
      changes of AD (senile plaques, neurofibrillary tangles and amyloid angiopathy)
      and SVDD (status lacunaris, status cribosus, leucoencephalopathy, micronecrosis
      and vascular fibrohyalinosis) in order to validate previous ApoE genotyping
      results in AD and to identify pre-clinical AD. Representative cerebral regions
      (cortex, gyrus cinguli, putamen, hippocampus, white matter) from 28 AD cases, 7
      SVDD and 38 non-neurological controls were studied using classical histological
      techniques and immunohistochemistry for tau protein and amyloid-beta. The
      frequency of the ApoE allele 4 was significantly increased not only in AD
      patients but also in aged controls. However, following a detailed
      histopathological examination was found 62% of this group to exhibit histological
      changes associated with AD in limited brain areas (entorhinal region, hippocampus
      and adjacent temporal cortex or entorhinal region and hippocampus, or only in the
      entorhinal region), but 87% of these cases were found to be ApoE4 positive. The
      significant differences found in the distribution of ApoE allele frequencies were
      more marked when these cases were excluded from the control group and included as
      AD cases. In contrast, the frequency of the ApoE allele 2 is significantly
      increased in SVDD patients. Using histological techniques we confirmed the
      clinical diagnoses of all cases and classified the AD patients according to the
      severity of cortical pathology related to AD, while re-grouping from the control
      group those cases which had no clinical history of the disease but exhibited
      typical AD and SVDD histological lessions which could be considered as "pre
      clinical" forms of these diseases.

PMID- 12214087
TI  - Amyloid-beta and treatment opportunities for Alzheimer's disease.
AB  - Proposed treatments of Alzheimer's disease (AD) are most likely to succeed if
      they are based on an understanding of the complex biology of AD and its effects
      on cognition. Treatments may target a single or multiple components of the
      complex pathology of AD with the hope that by affecting an individual component
      of AD pathology, the disease course can be affected. One such component is
      amyloid-beta (Abeta), a feature of the senile plaque. Abeta may be critical for
      inducing the pathology seen in AD. Accumulation of Abeta may result in a cascade
      of biochemical events leading to neuronal dysfunction, which may present
      opportunities for intervention at multiple different points to slow disease
      progression. Treatment may be directed towards decreasing Abeta production,
      increasing Abeta removal, and decreasing Abeta aggregation. Alternatively,
      treatment may be directed at more distal pathways by: modulating downstream
      events possibly due to Abeta such as free radical toxicity, decreasing
      inflammation, preventing cell membrane damage, restoring calcium homeostasis,
      preventing excitotoxicity, and blocking the cellular response to injury by
      inhibiting neuronal apoptosis. This review underscores the complex biology of
      Abeta specifically looking at the potential targets of therapeutics based on
      emerging knowledge of this biology.

PMID- 12214088
TI  - Oxygen free radical injury is sufficient to cause some Alzheimer-type molecular
      abnormalities in human CNS neuronal cells.
AB  - Cell loss and neuritic/cytoskeletal lesions represent two of the major categories
      of dementia-associated structural abnormalities in Alzheimer's disease (AD). Cell
      loss is ultimately mediated by apoptosis and mitochondrial DNA damage due to
      enhanced sensitivity to oxidative stress, but the mechanism responsible for the
      neuritic/cytoskeletal lesions including the abnormal proliferation of cortical
      neurites is not known. This study examines the potential role of oxygen free
      radical injury as a factor contributing to both cell death and neuritic sprouting
      cascades in AD. PNET2 human neuronal cells were treated with H2O2 (8 micro M to
      88 micro M) for 24 hours and then analyzed for viability, DNA damage, and pro
      apoptosis, survival, and sprouting gene expression and signaling. H2O2-treatment
      resulted in dose-dependent increases in cell death due to genomic and
      mitochondrial DNA damage associated with increased levels of 8-OHdG and the p53
      and CD95 pro-apoptosis genes, reduced levels of the Bcl-2 survival gene,
      activation of JNK and p38 stress kinases, and inhibition of PI3 kinase survival
      signaling. However, the H2O2-treated cells also manifested increased expression
      of growth and sprouting molecules, including GAP-43, nitric oxide synthase 3,
      neuronal thread protein (NTP; approximately 17 kD and approximately 21 kD forms),
      proliferating cell nuclear antigen, and phospho-Erk MAPK, and normal levels of
      the AD-associated approximately 41 kD NTP species, cyclin dependent kinase 5 (cdk
      5), and phospho-tau. In addition, the H2O2-treated cells had increased levels of
      p25, the catalytically active and stable cleavage product of p35, which regulates
      cdk-5 activity. Previous studies demonstrated p25 accumulation in AD brains and
      p25-induced hyperphosphorylation of tau and neuronal apoptosis. The findings
      herein suggest that oxygen free radical injury in human CNS neuronal cells is
      sufficient to cause some but not all of the pro-death and pro-sprouting molecular
      abnormalities that occur in AD.

PMID- 12214089
TI  - Evidence that oxidative challenges promote neuronal sprouting and cell cycle re
      entry.

PMID- 12214090
TI  - Generation of an apoptotic intracellular peptide by gamma-secretase cleavage of
      Alzheimer's amyloid beta protein precursor.
AB  - The amyloid beta protein precursor (AbetaPP) is sequentially processed by beta-
      and gamma-secretases to generate the Abeta peptide. The biochemical path leading
      to Abeta formation has been extensively studied since extracellular aggregates of
      amyloidogenic forms of Abeta peptide (Abeta42) are considered the culprit of
      Alzheimer's disease. Aside from its pathological relevance, the biological role
      of AbetaPP proteolysis is unknown. Although never previously described, cleavage
      of AbetaPP by gamma-secretase should release, together with Abeta, a COOH
      terminal AbetaPP Intracellular Domain, herein termed AID. We have now identified
      AID-like peptides in brain tissue of normal control and patients with sporadic
      Alzheimer's disease and demonstrate that AID acts as a positive regulator of
      apoptosis. Thus, overproduction of AID may add to the toxic effect of Abeta42
      aggregates and further accelerate neurodegeneration.

PMID- 12214091
TI  - Factors Affecting Pro- and Anti-Oxidant Properties of Fragments of the b-Protein
      Precursor (bPP): Implication for Alzheimer's Disease.
AB  - Oxidative stress may have a key pathogenetic role in neurodegenerative diseases
      including Alzheimer's disease (AD). While there is evidence that some amyloid-b
      (Ab) peptides can initiate oxidative stress at micromolar doses, there is also
      some evidence that oxidative stress increases the concentration of the b-protein
      precursor (bPP) and the potential for increased formation of the Ab peptides. The
      following studies were performed to test the hypothesis that fragments of bPP
      could be antioxidants and hence that oxidative stress might be an early event in
      AD. We found that several fragments of bPP, including the Ab peptides, inhibit
      ascorbate-stimulated lipid peroxidation (ASLP) in membrane fragment preparations
      of postmortem human brain. In contrast, other fragments of bPP enhance ASLP.
      These data indicate that bPP or fragments of bPP could play a key role in the
      redox status of cells and that alterations in bPP processing could have profound
      effects on the cellular response to oxidative stress.

PMID- 12214092
TI  - Oxidative Stress and the Amyloid Conundrum. What is the Connection?

PMID- 12214094
TI  - Tacrine (THA, Cognex(R)).

PMID- 12214093
TI  - Could Abeta and AbetaPP be Antioxidants?

PMID- 12214095
TI  - Commentary on William Summers Paper on Tacrine March 6, 2000.

PMID- 12214096
TI  - Revisiting Alzheimer's Disease from a New Perspective: Can "Risk Factors" Play a
      Key Role?
AB  - Alzheimer's disease (AD) has been intensively studied for decades, but why has
      its common pathological cause remained so enigmatic? Our studies have suggested
      that plaques and tangles occur spontaneously during aging as a result of a
      natural decline of energy metabolism and Ca2+ signaling, but not necessarily due
      to conventional pathogens. This view would lead to an unexpected outcome; that
      is, natural aging plays a more important role in neurodegeneration than is
      currently recognized. Does this model over-simplify the disease origin? We know
      that AD-type neurodegeneration typically occurs at the end stages of life when
      not only do plaques and tangles appear, but also many other bodily changes as
      well (bone loss and skin wrinkling, etc). Neurodegeneration differs from the
      latter changes mainly by "social" consequences, not by "physiological" origin. If
      neurodegeneration is a natural event, then why do only some people, but not
      others, develop AD? Obviously, additional factors are required for
      neurodegeneration to develop into AD. By comparing current models and ruling out
      other possibilities, we think that several known "risk factors" most likely play
      a critical role in the late-onset sporadic AD. These risk factors can exert their
      effects either by providing the conditions for ailing neurons to die (extended
      longevity and sedentary lifestyle), or by enhancing the individual's
      "vulnerability" to natural neurodegeneration (low synapse reserve). In this
      context, late-onset sporadic AD would be similar to many other age-related
      conditions where perhaps no single pathogen can be held exclusively responsible
      for most cases; rather, many risk factors are important to allow the initial
      defect to turn into clinical diseases. Accordingly, these factors should be the
      primary targets for AD prevention. Yet, some other AD cases, especially the early
      onset ones, may be complicated by the concomitant involvement of other diseases
      in the brain.

PMID- 12214097
TI  - Risk Factors and Mechanisms of Alzheimer's Disease Pathogenesis: Obviously and
      Obviously Not.

PMID- 12214098
TI  - Revisiting Alzheimer's Disease from a New Prospective: Can "Risk Factors" Play a
      Key Role?

PMID- 12214100
TI  - Risk Factors Versus Alzheimer's Disease or Symptoms Associated with Alzheimer's
      Disease.

PMID- 12214099
TI  - Aging: a Cause or a Risk for AD?

PMID- 12214101
TI  - How Important are Risk Factors in Alzheimer's Disease?

PMID- 12214102
TI  - Vitamin E Prevents Alzheimer's Amyloid beta-Peptide (1-42)-Induced Neuronal
      Protein Oxidation and Reactive Oxygen Species Production.
AB  - Amyloid beta-peptide (Abeta) is a 42-43 amino acid peptide known to accumulate in
      Alzheimer's disease (AD) brain. We previously reported that the neurotoxicity
      caused by Abeta is a result of its associated free radicals, which can play an
      important role in generating oxidative stress. Abeta(25-35)-associated oxidative
      stress-induced neuronal death in vitro is well established by many laboratories,
      including ours. However, the oxidative stress-induced by the full-length [Abeta(1
      42)] peptide is not well investigated. The protective effect of antioxidant
      vitamin E in full-length peptide-induced oxidative stress also has not been
      reported. Here, we report that the increased protein oxidation, reactive oxygen
      species (ROS) formation, and neurotoxicity induced by Abeta(1-42) in primary rat
      embryonic hippocampal neuronal culture are prevented by the free radical
      scavenger and antioxidant vitamin E. To test the hypothesis that vitamin E's
      protective effect may be due to inhibition of fibril formation, electron
      microscopy studies were undertaken. Vitamin E does not inhibit Abeta(1-42) fibril
      formation, suggesting that the neuroprotection afforded by this molecule stems
      from other processes, most probably through the scavenging of Ab-associated free
      radicals. These results may have implications on the treatment of Alzheimer's
      disease.

PMID- 12214103
TI  - Amyloid Fibril Toxicity Still Unresolved.

PMID- 12214104
TI  - Elimination of Amyloid beta Neurotoxicity.
AB  - Aggregation of the Alzheimer amyloid beta peptide (Abeta) Abeta1-42 forms
      neurotoxic fibrils. In contact with human neurons the fibrils cause rapid influx
      of external calcium through AMPA/kainate-channels. If this molecular mechanism
      reflects in vivo events, it could explain the pathogenesis of Alzheimer's
      disease; activation of AMPA/kainate channels is therefore a likely target for
      therapeutic intervention. Here we show that short antagonistic "decoy peptides",
      made of D-amino acids, eliminate this "calcium effect" of Ab1-42. Since
      chronically elevated calcium levels in the disease trigger activation of pathways
      that lead to neuron dysfunction and cell death, our decoy peptides are obvious
      candidates for drug development.

PMID- 12214105
TI  - Acetylcholinesterase Activity in the Mongolian Gerbil Brain after Acute Poisoning
      with Aluminum.
AB  - The aim of the present study was to evaluate the acetylcholinesterase activity in
      the brain of adult gerbils (Meriones unguiculatus) treated with aluminum. AlCl3 x
      6H2O was given "per os" in the amount of 3.7 g/kg body weight. The animals were
      killed 24, 48, 72 and 96 hours after the treatment. The activities of
      acetylholinesterase in the mitochondrial and microsomal fractions of cortex,
      hippocampus and thalamus as well as plasma levels of aluminum were measured.
      Acetylcholinesterase activity was significantly reduced in the mitochondrial and
      microsomal fraction of all investigated structures. Decrease of the enzyme
      activity was observed in the first 24 hours, and it was most prominent 48 hours
      after the administration of aluminum in the mitochondrial fractions when the
      activity of the enzyme was 31%, 29% and 18.9% of the control value, and after 24
      hours in the microsomal fractions when the activity of the enzyme was 43%, 48%
      and 32% of the control value in the cortex, hippocampus and thalamus,
      respectively. 96 hours after the administration of aluminum the activity of the
      enzyme was 63%, 57% and 31% of the value in the control group in mitochondrial,
      and 100%, 80% and 73% of the control value in microsomal fractions in cortex,
      hippocampus and thalamus. Plasma levels of aluminum were significantly elevated
      24 hours after administration of aluminum. After 48 hours the values were doubled
      in comparison with the control, 72 hours later plasma concentrations of aluminum
      were decreased, and after 96 hours they reached the value in the control group.
      We can conclude that a single oral dose (LD50) of aluminum causes the changes in
      the brain acetylcholinesterase activity. The changes are still present when the
      aluminum concentration in plasma is normalized.

PMID- 12214106
TI  - beta-Amyloid-Induced Tau Phosphorylation does not Correlate with Degeneration in
      Cultured Neurons.
AB  - Treatment of cultured neurons with beta-amyloid (Abeta) evokes multiple
      consequences, including calcium influx, production of reactive oxygen species
      (ROS), hyperphosphorylation of tau. Which of these events is the major cause of
      Abeta-induced neurodegeneration has been the subject of controversy. We undertook
      to determine whether or not the accumulation of hyperphosphorylated tau mediated
      neurodegeneration. Murine cortical neurons demonstrated increased phospho-tau
      immunoreactivity between 2-8 hr after treatment of murine cortical neurons with
      Abeta_25-35. Cultures underwent overall neurodegeneration between 8-16 hr as
      ascertained by phase-contrast microscopy, a commercial "live/dead" assay and
      externalization of phosphatidyl serine. Unexpectedly, however, the healthiest
      appearing neurons in Abeta-treated cultures contained relatively more phospho-tau
      immunoreactivity, while obviously degenerating neurons contained less;
      degenerating neurons often contained less phospho-tau immunoreactivity than did
      non-Abeta-treated control neurons. By contrast, accumulation of reactive oxygen
      species, previously demonstrated to mediate Abeta-induced neurodegeneration, was
      most prominent within visibly-degenerating neurons. These studies do not address
      the long-term consequences of PHF formation; however, they indicate that tau
      hyperphosphorylation, although a consequence of Abeta treatment, does not
      directly contribute to acute degeneration of cultured neurons.

PMID- 12214107
TI  - Brain Iron and Zinc Contents of German Patients with Alzheimer Disease.
AB  - Our first project aimed to determine the average values of Fe and Zn in normal
      German human brain (5 individuals, 10 brain parts). Determinations were carried
      out by instrumental neutron activation analysis in Berlin. Quality control
      measurements were performed using National Institute of Standard Technology
      standard reference materials. The present results show non-homogeneous
      distribution of Fe and Zn in normal human brain. Our second goal was to study the
      possible elemental concentration changes in German patients with Alzheimer
      disease (5 subjects, 10 brain regions). Fe and Zn values are found to be
      significantly changed in some AD brain regions compared to the controls. Another
      object of this work was to extend the method for the determination of elemental
      concentration not only in whole brain samples (high fat content) but - applying
      two types of solvent extraction - in lipid fraction and in brain tissue without
      lipid.

PMID- 12214109
TI  - Lower Counts of Astroglia and Activated Microglia in Patients with Alzheimer's
      Disease with Regular Use of Non-Steroidal Anti-Inflammatory Drugs.
AB  - Epidemiological studies have indicated that non-steroidal anti-inflammatory drugs
      (NSAID) may have some therapeutic effect in Alzheimer's disease (AD) and
      experimental studies have shown that microglia activation by Abeta-peptide (Abeta
      peptide. Furthermore, our results indicate that regular NSAID use is associated
      with significantly lower counts of astrocytes and a trend of lower counts of
      activated microglia in the brain tissue. The influence of NSAID use was noted in
      all ApoE genotypes however the trend of lower counts of glial cells with regular
      NSAID use was more marked in patients carrying the ApoE varepsilon 4/4 alleles.
      Based on our results one would anticipate that regular NSAID dosing could have a
      beneficial effect on the progression of the disease. However, the fact that we
      failed to observe significant differences for activated microglia might indicate
      an age or stage dependent difference in the glial response i.e. in their
      activation rate. More studies into age and stage related factors influencing the
      glial response are required if one is to devise novel pharmacological treatment
      strategies for AD.

PMID- 12214108
TI  - The Thr183Ala Mutation, Not the Loss of the First Glycosylation Site, Alters the
      Physical Properties of the Prion Protein.
AB  - The abnormal form of the prion protein has increased resistance to protease
      digestion and is insoluble in non-ionic detergents. The normal prion protein is
      modified by the non-obligatory addition of two N-linked glycans. One pathogenic
      mutation, Thr to Ala at residue 183 of the human prion protein, blocks addition
      of the first glycan to the Asp residue 181. This mutation has been reported to
      result in intracellular retention of the mutant protein and its acquisition of
      pathogenic properties, presumably due to the lack of the glycan. We report that
      the lack of the N-linked glycan at residue 181 is not responsible for the block
      in transport or the acquisition of pathogen-like properties, rather, the Thr to
      Ala mutation is itself the probable cause of the pathogenic phenotype.

PMID- 12214110
TI  - DNA Damage does not Correlate with Amyloid-beta-Plaques and Neurofibrillary
      Tangles in Familial Alzheimer's Disease Presenilin-1 [E280A] Mutation.
AB  - Recent studies have shown that the missense mutation in presenilin-1 [E280A]
      increases deposition of amyloid-beta (Abeta) and neurofibrillary tangle (NFT)
      formation. Indeed, we only observed 10 out of 48 FAD brain sections displaying
      TUNEL (+) labeling, and none with the classical apoptotic morphology. These
      results may indicate that DNA fragmentation is not a generalized phenomenon in
      early-onset FAD PS1 [E280A] patients or that neuronal cells are dying by a
      different mechanism of cell death. Taking together these findings suggest that
      Abeta and NFTs are not per se a causative factor to damage neuronal cells but
      their damage could be more related with individual neuronal vulnerability and
      brain aging

PMID- 12214111
TI  - Avoidance of Apoptosis in Alzheimer's Disease.
AB  - Internucleosomal DNA fragmentation, which is a well-known feature of apoptosis
      but not an absolute criterion for identifying apoptosis (1), has often been
      observed in the brain tissue of Alzheimer's disease (AD). However, classical
      apoptotic morphology such as nuclear condensation, membrane blebbing and
      apoptotic bodies are seldom seen in AD brain. In this issue of Journal of
      Alzheimer's Disease, Velez-Pardo et al. have reported the DNA fragmentation using
      terminal dUTP labeling (TUNEL) in postmortem brains of familial AD with
      presenilin-1 [E280A] mutation. Importantly, no classical apoptotic morphology has
      been observed also in the brains of presenilin-1 familial AD. Furthermore, Velez
      Pardo et al. have shown that there is no obvious correlation between DNA
      fragmentation and the severity of amyloid deposition as well as between DNA
      fragmentation and the severity of neurofibrillary tangle formation. An apoptotic
      pathway only takes several hours or at most a few days for completion. In the
      development of the lateral motor column of the chick embryo, 8,000 cells out of
      20,000 cells die, i.e. loss of 40% of the population occurs within 3 days (2).
      The fact that only 5% of the population in the lateral motor column is undergoing
      apoptosis at any particular time in this period (2) indicates that apoptotic
      pathway requires about 10 hours for completion. In a striking contrast with the
      physiologically programmed cell death, loss of 40% of the population occurs
      (3,000 neurons out of 7,000 neurons per 50 micron-thick section are lost) within
      10 years in the temporal cortex neurons of AD (3). If we suppose that 20-40% of
      neurons of the temporal cortex are undergoing degeneration at any given time in
      the course of AD, an individual neuron in the temporal cortex of AD requires 5-10
      years to die. Indeed, we can observe neurons displaying many of the features of
      apoptosis in AD. This fact argues that neurons in AD have mounted an effective
      defense to apoptotic death (an avoidance of apoptosis) rather than actual
      completion of apoptosis (4,5). It is noteworthy that nucleic acid oxidation
      occurs widely in vulnerable neuronal populations in AD (6) and oxidative damage
      can directly cause DNA fragmentation (7). Therefore, DNA damage possibly
      resulting from oxidative stress involves vulnerable neurons in AD beyond the
      distribution of amyloid deposition or neurofibrillary tangles, which may be
      related to neuronal cell death occurring independently of the classical AD
      pathology (3).

PMID- 12214112
TI  - Biphasic Effect of Calcium Influx on Tau Phosphorylation: Phosphorylation:
      Biphasic Effect of Calcium Influx on Tau Phosphorylation: Involvement of Calcium
      Dependent Phosphatase and Kinase Activities.
AB  - Conflicting data has emerged documenting decreased and increased levels of
      phospho-tau following calcium influx. Calcium influx achieved by treatment of SH
      SY-5Y human neuroblastoma with 1 micro M calcium ionophore A23187 in the presence
      of 0.1 mM extracellular calcium depleted phospho-tau levels within 30 min.
      However, extending ionophore treatment to 60 min raised phospho-tau levels beyond
      that of control levels. Total tau levels were unchanged throughout these
      treatments, indicating that the reduction in PHF-1 reflected sequential
      alterations in tau phosphorylation rather than total tau. More rapid accumulation
      of phospho-tau accompanied treatment with increased concentrations of ionophore
      (3 micro M) and extracellular calcium (0.9 mM). An inhibitor active against
      calcium-dependent kinase(s) prevented the increase in phospho-tau following
      calcium influx. These data underscore that phospho-tau levels represent the
      summation of kinase and phosphatase activities and indicate that net
      dephosphorylation or phosphorylation is dependent upon the extent and/or rate of
      calcium influx

PMID- 12214113
TI  - Glycogen Synthase Kinase-3 Modulates Neurite Outgrowth in Cultured Neurons:
      Possible Implications for Neurite Pathology in Alzheimer's Disease.
AB  - Glycogen synthase kinase-3 (GSK-3) is thought to play an important role in the
      hyperphosphorylation of tau, and possibly other proteins, in Alzheimer's disease
      (AD). However, the effects of GSK-3 on neuronal metabolism are still largely
      unknown. Here we describe that a low concentration of lithium, which can
      partially inhibit endogenous GSK-3, favored the extension of neurites from
      developing neurons, whereas a high concentration of lithium impaired neurite
      growth. Furthermore, the overexpression of exogenous active GSK-3 in neurons by
      infection with a defective herpesviral vector blocked neurite growth, which was
      not affected by either expression of inactive GSK-3 or just the herpesviral
      vector infection. Neurite extension was restored when neurons overexpressing
      exogenous active GSK-3 were incubated with lithium. These results are consistent
      with a role for GSK-3 in the regulation of cytoskeletal dynamics during neurite
      growth. Accordingly, up-regulation of GSK-3 may contribute to cytoskeletal
      pathology within neurites in AD.

PMID- 12214114
TI  - PHF-Tau from Alzheimer Brain is Rapidly Dephosphorylated and Degraded When
      Injected into Neurons in situ.
AB  - Accumulation of abnormally modified tau protein (PHF-tau) is the principal
      intracellular lesion in a variety of neurodegenerative diseases, including
      Alzheimer's Disease (AD), but the cellular mechanisms underlying this
      accumulation are unknown. In this study, the cellular metabolism of PHF-tau
      purified from AD brain was investigated by microinjecting it into identified
      central neurons of the lamprey, a lower vertebrate. Dephosphorylation of 2
      critical epitopes (the PHF-1 and TAU-1 sites), occurred within a few hours of PHF
      tau microinjection, while proteolysis was complete by 2 days. These results
      constitute the first demonstration of the intracellular degradation of PHF-tau in
      an experimental in vivo system and suggest that the degradation of PHF-tau in
      situ is preceded by dephosphorylation. They also suggest that intracellular PHF
      tau accumulation is primarily due to the failure of normal dephosphorylation
      and/or proteolytic mechanisms during neurofibrillary degenerative disease.

PMID- 12214115
TI  - Cell-Type-Specific Differences in Age-Related Changes of DNA Repair in the Mouse
      Brain - Molecular Basis for a New Approach to Understand the Selective Neuronal
      Vulnerability in Alzheimer's Disease.
AB  - Despite intensive research over the last decades, the molecular basis of the
      selective neuronal vulnerability in Alzheimer's disease (AD) is still largely
      unknown. In this context we have recently shown by means of quantitative
      autoradiography that presumably all types of neurons in the mouse brain suffer an
      age-related decrease in the rate of mitochondrial DNA synthesis, while in
      contrast only some distinct types of neurons showed a decrease in the rate of
      spontaneous overall nuclear DNA repair measured as unscheduled nuclear DNA
      synthesis. Most strikingly, there was a highly positive correlation to be found
      between that group of neurons in the mouse brain showing the age-related decrease
      in the rate of spontaneous overall nuclear DNA repair (pattern X) and the pattern
      of neurons in the human brain which - according to the literature - are affected
      by the formation of neurofibrillary tangles in AD (pattern Y). To minimize the
      risk that this correlation was a result of mere chance based on the selection of
      the nine types of neurons investigated thus far, in the present study nine
      further types of neurons in phylogenetically different regions of the mouse brain
      were investigated by using the same method. An age-related decrease in the rate
      of spontaneous overall nuclear DNA repair was found only for projection neurons
      of brain areas with a more plastic, variable and/or malleable structure over
      phylogenesis but neither for projection neurons of brain areas with a more rigid,
      invariant and/or conservative structure over phylogenesis nor for interneurons.
      The obtained results confirmed the highly positive correlation between the
      aforementioned patterns X and Y. Together with a wealth of data from the
      literature regarding age-related neuron loss in both the rodent and the human
      brain, these results may indeed indicate a new approach for understanding the
      selective neuronal vulnerability in AD.

PMID- 12214116
TI  - Increased Cyclin G1 Immunoreactivity During Alzheimer's Disease.
AB  - Numerous proteins are alternatively expressed in neurons and glia during
      Alzheimer's disease (AD) and may contribute to the regulation of neuronal cell
      death or function in regenerative responses to neuronal injury. A recently
      described member of the cyclin gene family, cyclin G1, is expressed in post
      mitotic neurons in the adult rat brain and is expressed at high levels after
      brain injury. In the current study we examined the expression and subcellular
      distribution of cyclin G1 in non-demented adult and AD brain. While low levels of
      cyclin G1 protein were observed in pyramidal neurons in control brain, abundant
      cyclin G1 immunoreactivity was present in the cytoplasm of pyramidal neurons in
      the neocortex and hippocampus of AD brain. Cyclin G1 immunoreactivity was not
      present in cells containing neurofibrillary pathology. Our results indicate that
      cyclin G1 is expressed in human adult brain and exhibits increased
      immunoreactivity in the cytoplasm of pyramidal neurons in AD. In addition, cyclin
      G1 immunoreactivity was not evident in cells containing cytoskeletal pathology.

PMID- 12214117
TI  - Decreased Levels of Amyloid-beta 1-42 in Cerebrospinal Fluid of Creutzfeldt-Jakob
      Disease Patients.
AB  - Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disease caused by the
      prion protein. In the search for biochemical markers for CJD, cerebrospinal fluid
      (CSF) of 101 patients was analysed for 14-3-3 protein, hTau-protein and amyloid
      beta 1-42 (Abeta_1-42). The 14-3-3 test had a specificity of 91.5% and a
      sensitivity of 84%. The hTau test resulted in 95% specificity and 74%
      sensitivity, when a cut-off of 1530 pg/ml was used. Abeta_1-42 detection in CSF
      of 29 probable or definite CJD patients revealed significantly decreased values
      (p=0.01) compared to a group of 22 neurological controls. In the CJD patients a
      mean of 319+/-102 pg/ml was found. In the neurological control group a mean of
      553+/-268 pg/ml was observed. In patients with a false positive 14-3-3 test (n=5)
      a mean of 716+/-441 pg/ml was found. We conclude that determination of Abeta_1-42
      levels in CSF can be useful for identifying false positive 14-3-3 results in
      suspected CJD patients. We also compared the presence of senile plaques and the
      Abeta_1-42 levels in CSF of CJD patients. No clear correlation between them was
      found in this series. This signifies that the deceased Abeta_1-42 levels in CSF
      are not just due to plaque retention but that other mechanisms must also play a
      role.

PMID- 12214118
TI  - Dietary links to Alzheimer's disease: 1999 update.
AB  - With the republication of Grant (18), the first paper providing epidemiologic
      evidence linking diet to the development of Alzheimer's disease (AD), it is an
      appropriate time to review the findings and hypotheses therein in light of the
      subsequent literature. The main findings, that dietary fat and energy in old age
      are high risk factors, while fish and cereals are risk-reduction factors, have
      been supported in various recent epidemiologic studies. Diet contributes to the
      development of AD through modulating oxidative stress and inflammation, which is
      also linked to oxidative stress, but may also arise from series 2 prostaglandins.
      Thus, as one ages, dietary modifications and additional supplements designed to
      reduce free radical production and inflammation provide a significant measure of
      reduction in risk for the development of AD.

PMID- 12214119
TI  - Diet and oxidative stress: a novel synthesis of epidemiological data on
      Alzheimer's disease.

PMID- 12214120
TI  - Nicotinic acetylcholine receptors in Alzheimer's disease.
AB  - Nicotinic cholinoceptive dysfunction associated with cognitive impairment is a
      leading neurochemical feature of Alzheimer's disease. There-fore, nicotinic
      acetylcholine receptors have attracted considerable interest as potential
      therapeutic targets. The deficit of nicotine binding sites in Alzheimer's disease
      may be related to alterations of nicotinic receptor synthesis on the levels of
      (i) transcription, (ii) translation and post-translational modifications, (iii)
      receptor transport and turnover, including membrane insertion. Current approaches
      aim at the elucidation of molecular changes at all three levels. Although a
      comprehensive picture has not yet been achieved, currently available data can be
      summarized as follows: (i) there are no changes at the level of transcription of
      subunit mRNAs studied so far, (ii) evidence is accumulating for a distinct
      decrease on the protein level in the expression especially of the alpha 4
      subunit, and (iii) preliminary findings point to a possible correlation of
      cytoskeletal changes (hyperphosphorylation of tau-protein) with decreased
      nicotinic acetylcholine receptor expression.

PMID- 12214121
TI  - Nicotinic cholinergic receptor deficits in Alzheimer's disease: where's the
      smoke?
AB  - Receptor binding studies have uniform-ly found a significant reduction in the
      density of neuronal nicotinic cholinergic receptors in postmortem tissue obtained
      from Alzheimer's Disease (AD) patients. Nicotine is widely recognized as an
      pharmacological agent that facilitates cognitive performance in human smokers as
      well as preclinical models utilizing rodents or non-human primates. Furthermore,
      epidemiological studies have consistently shown that the incidence of
      neurodegenerative diseases such as AD and Parkinson's Disease is lower in
      cigarette smokers than age-matched controls. These findings have prompted
      speculation that brain nicotinic receptors could be important therapeutic targets
      for Alzheimer's Disease. However, many questions remain with regard to the
      specificity and significance of the findings that have been reported with brain
      nicotinic receptors and AD. Few studies have controlled for the potential
      influence of cigarette smoking, which increases the density of nicotinic
      receptors in human smokers. Questions also remain concerning alterations in
      individual nicotinic receptors subtypes as well as the regional variability of
      the deficits previously reported in AD. Therefore, although the findings related
      to nicotinic receptors and AD to this date are intriguing, they appear to have
      raised more questions than they have answered.

PMID- 12214122
TI  - Cholinergic muscarinic receptor signaling by the phosphoinositide signal
      transduction system in Alzheimer's disease.
AB  - Recent years have seen the advent of new methods capable of measuring the
      activity of receptor-coupled, G-protein-mediated, phosphoinositide second
      messenger production in membranes prepared from postmortem human brain.
      Considering the interest in treating Alzheimer's disease (AD) patients with
      cholinergic agonists, several investigations have used this new methodology to
      analyze the functional state of cholinergic muscarinic receptors coupled to
      phosphoinositide signaling directly in AD brain. Several, but not all, reports
      indicate that cholinergic agonist-induced phosphoinositide signaling is severely
      impaired in AD, potentially due to impaired activation of the receptor-coupled G
      protein. Additionally, deficits in AD also have been reported in the two second
      messenger pathways activated following phosphoinositide hydrolysis, inositol
      1,4,5,-triphosphate receptor binding and protein kinase C activation, indicating
      further that phosphoinositide signaling is impaired in AD. Sources of limitations
      in current methodologies and issues for further exploration are discussed.
      Speculation concerning potential links between cholinergic receptor-linked
      signaling and early events in the formation of amyloid plaques and
      neurofibrillary tangles is provided. Especially intriguing is the potential for
      the development of synergistic neurotoxicity where deficits of phosphoinositide
      signaling and increased production of A beta interact to exacerbate alterations
      in each process that occur in AD, leading to a feed-forward cycle of progressive
      neuronal dysfunction.

PMID- 12214123
TI  - The diagnosis of Alzheimer's disease.
AB  - Dementia constitutes a growing public health crisis. Early and accurate diagnosis
      of dementia is essential in order to provide patient and family counseling and
      appropriate treatment, including with specific antidementia drugs as they become
      increasingly available. Age-related cognitive decline, as compared with dementia,
      does not seriously interfere with usual activities. The optimal approach to early
      detection of dementia is clinical examination that incorporates information from
      a reliable collateral source about how the patient's cognitive abilities have
      declined relative to past performance. Alzheimer's disease (AD), the most common
      cause of dementia, can be diagnosed clinically with high accuracy (=85%) using
      standardized criteria. Even incipient AD can be detected with clinical methods
      alone. Although the typical picture of AD is characterized by gradual onset and
      progression of memory and other cognitive deficits, in other respects the disease
      is marked by heterogeneity. Early and late-onset AD represent the most easily
      recognized subtypes. Research continues towards characterizing a biologic marker
      but, as of yet, no candidate marker surpasses the high diagnostic accuracy of
      clinical assessments alone. At present, the diagnosis of AD rests primarily in
      the hands of the clinician.

PMID- 12214124
TI  - Estradiol: a protective and trophic factor in the brain.
AB  - In recent years our appreciation that estradiol is truly a pleiotropic hormone
      has grown dramatically. We will review the findings that suggest that estrogens
      may exert important non-reproductive actions on the brain. These studies provide
      important insights into the clinical effects of estrogen replacement therapy on
      age- and disease-related processes in the brain. We will also discuss the
      multiple cellular and molecular mechanisms that may underlie estradiol's
      neurotrophic and neuroprotective effects.

PMID- 12214125
TI  - Neurite-outgrowth regulating functions of the amyloid protein precursor of
      Alzheimer's disease.
AB  - Many studies have shown that breakdown of the amyloid protein precursor (APP) to
      produce the amyloid protein is an important step in the pathogenic mechanism
      which causes Alzheimer's disease (AD). However, little is known about the normal
      function of APP. Developmental studies show that APP expression increases during
      the period of brain development when neurite outgrowth and synaptogenesis is
      maximal. APP is expressed highly within growing neurites and in growth cones, and
      purified APP has been shown to stimulate neurite outgrowth from cells in culture.
      Thus APP may regulate neurite outgrowth or synaptogenesis in vivo. APP is
      actively secreted from many cells, and the C-terminally secreted APP has been
      shown to associate with components of the extracellular matrix, such as the
      heparan sulphate proteoglycans (HSPGs). Two putative heparin-binding domains on
      APP have been reported. Binding of HSPGs to an N-terminal heparin-binding domain
      (HBD-1) stimulates the effect of substrate-bound APP on neurite outgrowth. In the
      mature nervous system, APP may play an important role in the regulation of wound
      repair. It is highly likely that studies on the normal functions of APP will shed
      further light on aspects of the pathogenesis of AD.

PMID- 12214126
TI  - Is understanding the biological function of APP important in understanding
      Alzheimer's disease?
AB  - The presence of mutations around the A beta sequence in APP provides strong
      argument for the involvement of APP, and A beta in particular, in pathogenesis of
      Alzheimer's disease (AD). In vitro studies demonstrated that A beta may cause
      neuronal death, supporting the hypothetical involvement of A beta in
      neurodegeneration in AD. However, concentrations of A beta required for neuronal
      death are nonphysiologically high. Nevertheless, the predominant idea in the
      field is that it is sufficient to postulate A beta as a major culprit in AD
      development. The question we pose is whether the potentially important
      involvement of A beta precludes the etiological (primary) involvement (not
      pathological, i.e., secondary) of APP functions. We do not have an adequate
      answer to this question. Current knowledge about APP functions indicates that APP
      is critically required for the maintenance of neuronal and synaptic structure and
      function. Because AD is a disease of neuronal and synaptic deterioration, APP may
      be involved during the course of AD pathogenesis, perhaps secondarily. To ponder
      the question whether APP may be etiologically involved in AD, much needs to be
      learned about APP functions. This article is intended to provide a foundation for
      this challenging task.

PMID- 12214127
TI  - Elevated levels of tau in cerebrospinal fluid: implications for the antemortem
      diagnosis of Alzheimer's disease elevated levels of tau in cerebrospinal fluid:
      implications for the antemortem diagnosis of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a heterogeneous group of dementias characterized by
      progressive cognitive impairments as well as by the accumulation of abundant
      extracellular deposits of Ass and intra-neuronal neurofibrillary lesions in
      selective-ly vulnerable regions of the AD brain. The latter abnormalities (e.g.
      neurofibrillary tangles, dystrophic neurites, neuropil threads) are aggregates of
      paired helical filaments (PHFs) formed from altered tau proteins (PHFtau).
      Although PHF tau and normal central nervous system (CNS) tau are phosphorylated
      at nearly the same sites, PHFtau is phosphorylated to a greater extent, and
      alterations in the activity of CNS kinases and phosphatases most likely
      contribute to the pathogenesis of PHFtau. Since the abundance of neurofibrillary
      lesions correlates with the dementia in AD, the generation of PHFtau and the
      formation of neurofibrillary lesions may be part of a cell death pathway leading
      to massive neuron loss and dementia in AD. Building upon these and other insights
      into altered tau metabolism in AD, a series of studies suggest that the diagnosis
      of AD may be supported in living patients by determining the concentration of tau
      in cerebrospinal fluid (CSF). We review these promising studies here, and discuss
      them in the context of current understanding of the pathobiology of AD.

PMID- 12214128
TI  - Tau protein in normal and Alzheimer's disease brain.
AB  - In 1975, Weingarten and colleagues isolated a protein factor that was able to
      induce microtubule formation. They called this factor tau (t). Some ten years
      later a new era of research on this microtubule-associated protein was launched
      when several groups almost simultaneously discovered that tau was the predominant
      protein component of the paired helical filaments (PHFs) and neurofibrillary
      tangles (NFTs) which are characteristic pathological lesions of the Alzheimer's
      disease brain. Subsequent findings that PHF-tau isolated from Alzheimer's disease
      brain was phosphorylated to a greater extent than non-PHF tau, led to extensive
      investigation into the posttranslational modifications (mainly phosphorylation)
      of tau in normal and Alzheimer's disease brain. The present review highlights the
      literature concerning the normal functioning and processing of tau protein, and
      examines the evidence for the involvement of the abnormal posttranslational
      processing of tau in the pathology of Alzheimer's disease. Finally, speculation
      as to the relationship between abnormal processing of tau, other subcellular
      abnormalities seen in Alzheimer's disease, and the pathological causes of the
      disease are discussed.

PMID- 12214129
TI  - Tau protein in normal and Alzheimer's disease brain: an update.
AB  - Tau is a microtubule-associated protein that, in a hyperphosphorylated form,
      comprises the main component of the paired helical filaments and neurofibrillary
      tangles found in Alzheimer's Disease (AD) brain. It is therefore important to
      understand the normal functioning and processing of tau protein, and the abnormal
      posttranslational processing of tau in AD pathology. In 1996, Johnson and Jenkins
      reviewed the literature on the biochemistry, function, and phosphorylation of tau
      in normal and AD brain. Since that time, numerous publications have come out
      further elucidating the properties of tau. The present review updates the topics
      originally covered in the 1996 review, as well as presents a number of new
      topics. For example, mutations in the tau gene have been found in several non-AD,
      autosomal dominant neurodegenerative disorders that exhibit extensive
      neurofibrillary pathology. In addition, there is increasing evidence that tau may
      be involved in signal transduction, organelle transport, and cell growth,
      independent of its microtubule-binding functions. Taken together, the research
      reviewed here demonstrates that tau is a very complex protein with various
      functions that are intricately regulated. It is clear that more research is
      required to completely understand the functions and regulation of tau in normal
      and AD brain.

PMID- 12214130
TI  - Association of novel and established polymorphisms in neuronal nicotinic
      acetylcholine receptors with sporadic Alzheimer's disease.
AB  - Since the loss of cholinergic neurons in the Alzheimer's disease (AD) brain was
      first reported, considerable evidence in vivo and in vitro has accumulated in
      support of the cholinergic hypothesis of AD. The hypothesis is greatly supported
      by the fact that the most promising drugs against AD are inhibitors of
      acetylcholinesterase (AChE). To identify the possible mutations and/or
      polymorphisms of neuronal nicotinic acetylcholine receptor (nAChR) genes related
      to the pathogenesis of sporadic AD, we have performed mutational analyses of the
      major neuronal nAChR genes (CHRNA3, 4, 7 and CHRNB2) expressed in central nervous
      system. Allelic analysis showed association of specific silent or intronic
      polymorphisms of the CHRNA3 and CHRNA4 genes and AD. Two novel missense point
      mutations, Ser413Leu in the CHRNA4 gene and Gln397Pro in the CHRNB2 gene, were
      identified in two different AD cases but were not found in other AD cases and
      controls. These findings suggested that genetic polymorphisms of the neuronal
      nAChR genes might be related to the pathogenesis of sporadic AD.

PMID- 12214131
TI  - Assessing olfactory abilities with the University of Pennsylvania smell
      identification test: a Rasch scaling approach.
AB  - The strategy of delaying or retarding the progression of Alzheimer's disease
      requires early diagnosis and treatment. Previous research indicates that
      measurement of changes in olfaction and cognition will play an important role in
      the early detection of AD and in the monitoring of therapy effectiveness. Using
      the data of 177 subjects, our objective was to study the measurement properties
      of the University of Pennsylvania Smell Identification Test (UPSIT) using a Rasch
      scaling framework. The results indicate that the UPSIT can yield a linear,
      unbiased, and unidimensional Rasch measure of human smell recognition abilities.
      As expected, olfactory recognition ability decreased with age, and at the rate of
      about 0.05 Logits per year. Also, Alzheimer's patients showed a decrease in smell
      recognition equivalent to that experienced by healthy subjects over the course of
      30 years. Hormone replacement therapy was not found to affect healthy women's
      olfactory recognition ability. Additional diagnostic information can be extracted
      from the analysis of incorrect responses patterns that is relevant to group
      membership.

PMID- 12214132
TI  - Serum pentosidine as an indicator of Alzheimer's disease.
AB  - Pentosidine, an advanced glycation end product (AGE), was assayed by HPLC in
      serum proteins from patients with Alzheimer type dementia (AD), patients with
      diabetes mellitus (D), and healthy (C) age-matched old subjects (mean age from
      each group = 84 years). Serum pentosidine was significantly different between the
      three groups despite similar renal function (serum creatinine < 160 micromol/L).
      In all groups of patients, pentosidine was independent of glycated hemoglobin
      (HbA1C) and the early glycation marker fructosamine and appeared to be an
      independent marker, mainly bound to serum albumin. Pentosidine could be an
      important factor useful for the diagnosis of Alzheimer's disease.

PMID- 12214133
TI  - Thyrotropin releasing hormone (TRH) in the hippocampus of Alzheimer patients.
AB  - Thyrotropin-releasing hormone (TRH) is best known for its hypothalamic
      neuroendocrine role in regulating thyroid function. In extra-hypothalamic regions
      in vitro, we have shown TRH to have a protective effect against synaptic loss and
      neuronal apoptosis. A role for TRH in Alzheimer's disease (AD) has not been
      established previously. In this study, we examined the content of the TRH peptide
      in the hippocampus of elderly controls (n=5) and AD patients (n=7) by
      radioimmunoassay (RIA). The TRH concentration was decreased in the AD hippocampus
      compared to normal elderly controls (p < 0.01). In a separate series of
      experiments utilizing primary cell cultures made from rat hippocampus, TRH
      peptide concentration was depleted by the addition of TRH antiserum. TRH
      withdrawal was found to enhance the activity of glycogen synthetase kinase-3 (GSK
      3beta), a critical enzyme necessary for the phosphorylation of tau, as well as
      the phosphorylation of the tau protein itself. This TRH depletion induced
      upregulation in phosphorylation that was observed to initiate axonal retraction
      in cultured neurons. These data suggest that TRH within the hippocampus can
      regulate the activity of various proteins by phosphorylation/dephosphorylation
      that may be involved in the pathogenesis of AD.

PMID- 12214134
TI  - Searching for an in vivo site for nascent amyloid fibril formation.

PMID- 12214135
TI  - Multi-functional capability of proteins: alpha1-antichymotrypsin and the
      correlation with Alzheimer's disease.

PMID- 12214136
TI  - Controversies over p25 in Alzheimer's disease.

PMID- 12214137
TI  - Disease transmission by blood products: past, present and future.
AB  - Transfusion of blood and blood products has been associated with transmission of
      infectious agents. However, it is probable that blood products are currently very
      safe and that pooled virus-inactivated products from remunerated donors are now
      safer than untreated single voluntary donor components. Although the transmission
      events of the past and the present are reasonably well understood, reliance on a
      linear approach to predict safety in the future is open to criticism. Indeed, it
      was not possible to predict the extent or consequences of the AIDS epidemic or of
      hepatitis C transmission. Moreover, although variant Creutzfeldt-Jakob disease
      (vCJD) may not be transmitted to any large extent by transfusion of manufactured
      blood products, this will be due more to good fortune than good judgement - this
      agent could have escaped the screening, testing and eradication methods on which
      current confidence in blood product safety depends. Similarly, the emergence of a
      highly resistant non-enveloped virus, or even of another previously unrecognised
      disease-causing agent, could result in new threats from transfusion of blood
      components and products. The ecology of blood transfusion is exquisitely
      sensitive to variations in starting conditions, a situation typical of a chaotic
      rather than a linear system. Seemingly trivial events, often apparently unrelated
      to blood transfusion, have had enormous consequences in this field. Whatever the
      events that introduced simian immunodeficiency virus to humans or scrapie to
      cattle, they were a long way from those involved in the manufacture of blood
      products. In such a setting, reliance on methods that deal effectively with known
      threats (such as encapsulated viruses and bacteria) without adequate
      investigation and management of the intrinsic sensitivity to unpredictable
      events, leaves open the possibility of further infections emerging in the future.
      It is this reality that will ultimately result in the eradication of the
      transfusion of donor-derived blood and blood products in the developed world. In
      addition, all infections with a long disease-free incubation period in the host
      that can be transmitted in blood will eventually be over-expressed in groups that
      are exposed to blood either recreationally or professionally. As in the past,
      this could have occurred before testing or decontamination processes have been
      developed for emerging pathogens. Failure to be able to rely on completely risk
      free donors, in both the voluntary and non-voluntary sides of the blood industry,
      continues to offer the potential for the transmission of infectious diseases in
      the future.

PMID- 12214138
TI  - The evidence behind inhibitor treatment with porcine factor VIII.
AB  - Factor VIII auto- and alloantibodies neutralise porcine factor VIII to a lesser
      extent than factor VIII of human origin. The reduced reactivity of the porcine
      molecule, predominantly due to sequence variation in the A2 and C2 domains, has
      been the rationale for using porcine factor VIII to secure haemostasis for
      patients with factor VIII inhibitors. Porcine factor VIII has been shown to
      provide effective haemostatic control particularly for patients with intermediate
      inhibitor titres with limited porcine cross-reactivity. Small studies have
      indicated porcine factor VIII can be associated with desensitisation of some
      factor VIII inhibitor patients. Porcine factor VIII has been shown to produce
      mild platelet agglutination, an effect that may enhance its efficacy. Adverse
      reactions are dose-related and do not preclude safe and effective long-term home
      use for the subgroup of inhibitor patients with modest or absent anamnestic
      response. Efforts to secure source plasma free of viral markers, particularly
      porcine parvovirus, have limited the supply of this therapeutic product.

PMID- 12214139
TI  - Evidence for the use of activated prothrombin complex concentrates (aPCCs) in the
      treatment of patients with haemophilia and inhibitors.
AB  - FEIBA and Autoplex T have been used to control bleeding in patients with factor
      VIII or IX inhibitors for over 25 years. The major components of FEIBA are
      thought to be activated factor X and prothrombin, whereas the main active
      components in Autoplex T are thought to be activated factors IX and VII. Both
      products have been found to effectively control approximately 80% of bleeds
      involving joints and soft tissues. Published experience of their use in surgery
      is limited. Thrombotic complications have been reported with high dose FEIBA
      therapy and have led to maximum dosage guidelines for this product.

PMID- 12214140
TI  - The evidence behind inhibitor treatment with recombinant factor VIIa.
AB  - Over the past 10 years considerable use has been made of recombinant factor VIIa
      (rFVIIa) for the treatment of patients with inhibitors to coagulation factors.
      During this time, its place in the management of acute bleeds and surgery has
      become better defined. Although pharmacokinetic studies report the half-life of
      rFVIIa as 2.7 h, there is considerable intersubject variability. Moreover, rFVIIa
      is cleared more rapidly in children than in adults. Assays for the measurement of
      rFVIIa plasma levels are not readily available in clinical diagnostic
      laboratories, although there is evidence that plasma FVII:C levels, measured by a
      one-stage prothombin-based assay, reflect the plasma concentration of rFVIIa:C.
      The level of FVII:C required to achieve haemostasis in different clinical
      circumstances remains uncertain. In order to overcome the logistic difficulties
      of repeated frequent bolus injections, and potentially to minimise usage,
      administration of rFVIIa by continuous infusion has been reported. However, there
      is some uncertainty as to whether continuous infusion of rFVIIa has similar
      therapeutic efficacy to an equivalent total dose administered by bolus
      injections. The extensive clinical experience with rFVIIa in haemophilic patients
      with inhibitors has been recorded in descriptive accounts of the Compassionate
      Use Programme and the Emergency Use Study. On the basis of the apparent clinical
      efficacy and safety reported in these studies, prospective randomised trials of
      different dose regimens have been undertaken for the treatment of acute bleeds
      and surgery. These have helped to define the minimum dose needed to achieve
      haemostasis. There remains considerable uncertainty about the minimal effective
      dose and appropriate duration of therapy in different clinical circumstances.
      There is therefore a need for the development of evidence-based guidelines for
      the use of rFVIIa in bolus and continuous infusion regimens in different
      settings, and for the therapeutic value of measuring plasma concentrations of
      rFVIIa, to facilitate the optimal use of this product. Furthermore, additional
      randomised clinical trials will help ensure that rFVIIa is used in the most
      clinically and cost effective way.

PMID- 12214141
TI  - The 2000 United Kingdom Haemophilia Centre Doctors' Organisation (UKHCDO)
      inhibitor guidelines.
AB  - The UKHCDO inhibitor guidelines address the diagnosis and management of patients
      with haemophilia A, haemophilia B and acquired haemophilia. Recommendations are
      based on best current practice as reflected in the published evidence base. Many
      current treatment strategies are based on uncontrolled observations highlighting
      the need for well designed controlled studies.

PMID- 12214142
TI  - Recombinant factor VIIa in the management of surgery and acute bleeding episodes
      in children with haemophilia and high-responding inhibitors.
AB  - The development of inhibitors to therapeutic factor concentrates in children with
      haemophilia A or B is a troublesome complication of factor replacement therapy.
      Immune tolerance protocols have been developed to eliminate the inhibitors, and
      these are successful in approximately 80% of children. However, acute bleeding
      episodes require treatment with a factor (F)VIII or FIX bypassing agent to
      prevent an anamnestic rise in the inhibitor level before starting immune
      tolerance. In addition, central venous access is necessary to help parents
      administer frequent, high dose factor concentrate. In view of the benefits of
      rFVIIa seen in adults, a study has been carried out on the use of this agent as
      haemostatic cover in children with severe FVIII or FIX deficiency with high
      responding inhibitors. Information was obtained retrospectively from the National
      Children's Hospital, Dublin and Great Ormond Street Hospital, London. Twelve
      children aged 1-16 years were treated successfully with rFVIIa to prevent
      surgical bleeding in 20 surgical procedures. Minor post-operative haematomata
      developed in 2 of 20 cases after regular rFVIIa therapy had been discontinued. In
      both cases, resolution of bleeding occurred after a short course of rFVIIa. Three
      children experienced a total of six life- or limb-threatening bleeds. All
      bleeding episodes resolved with regular rFVIIa treatment, although topical fibrin
      glue was needed in one child with a frenulum tear. The rFVIIa therapy was well
      tolerated and there was no evidence of any treatment-related complications. In
      conclusion, rFVIIa is the treatment of choice for the management of surgery and
      acute life- or limb-threatening bleeding in children with haemophilia and high
      responding inhibitors.

PMID- 12214143
TI  - High cost patients and the consortium approach.
AB  - The Pan-Thames Haemophilia Consortium was established to provide coherent
      regional planning of haemophilia services. The Expert Advisory Group is a
      clinical reference point for the consortium and was established to consider
      specifically elective high cost treatment programmes. An audit of the first year
      of consortium activity demonstrated that patients receiving high cost therapy
      represented 1.6% of the patient population and received 16% of the entire
      treatment budget. The Pan-Thames Consortium provides focused commissioning
      expertise and a model for national commissioning of haemophilia services.

PMID- 12214144
TI  - Economic impact of treating inhibitor patients.
AB  - A literature review of the economics of managing haemophilia patients with
      inhibitors was conducted. It showed that haemophilia with inhibitors places a
      burden on the healthcare system and on the patient. Use of rFVIIa compared to
      'usual therapy' is associated with improvements on a number of outcomes,
      including speed of bleed resolution, duration of pain, and quality of life. The
      extra costs of rFVIIa can be justified by the additional benefits achieved: For
      example, the extra costs required to achieve a gain of one quality adjusted life
      year (QALY) in children with inhibitors has been shown to be comparable with that
      for other reimbursed healthcare strategies. Future research could focus on
      expanding our understanding of the impact of accelerated bleed resolution on long
      term sequelae, including need for surgery and quality of life.

PMID- 12214145
TI  - General haemostatic agents--fact or fiction?
AB  - Haemophilia is the most serious bleeding model that nature has provided us with,
      indicating the importance of factor FVIII and FIX in haemostasis. According to
      current knowledge, haemostasis is initiated by the formation of a complex between
      tissue factor (TF), exposed as a result of a vessel wall injury, and activated
      FVII (FVIIa) that is normally present in circulating blood. The TF-FVIIa
      complexes convert FX into FXa on the TF-bearing cell. FXa then activates
      prothrombin into thrombin. This limited amount of thrombin activates FVIII, FV,
      FXI and platelets. Thrombin-activated platelets change shape, resulting in
      exposure of negatively-charged phospholipids, which form the perfect template for
      full thrombin generation involving FVIII and FIX. In patients with haemophilia
      FVIII or FIX is missing. These individuals generate only initial limited amounts
      of thrombin as its generation is dependent on the presence of FVIII and FIX. Full
      thrombin generation is necessary for complete activation of FXIII and thrombin
      activatable fibrinolytic inhibitor to occur. Furthermore, full thrombin
      generation is important for the fibrin structure of the haemostatic plug. In the
      case of impaired thrombin generation, fibrin plugs will be loose and highly
      permeable. Such fibrin plugs are easily dissolved by normal fibrinolytic activity
      and thus prevent full and maintained haemostasis from occurring. The addition of
      rFVIIa to FVIII- or FIX-deficient plasma has been shown to increase thrombin
      generation in a cell-based in vitro model. Furthermore, extra rFVIIa was found to
      normalise fibrin clot permeability in vitro and to tighten the fibrin structure
      as studied by three-dimensional confocal microscopy. These findings indicate that
      administration of rFVIIa is capable of compensating for the lack of FVIII and
      FIX. Accordingly, the administration of exogenous rFVIIa has been found to stop
      bleedings in haemophilia patients and, provided it is given in doses high enough,
      to allow major surgery to be performed in severe haemophiliacs with inhibitors.
      As rFVIIa enhances thrombin generation on already activated platelets, it has
      been suggested that rFVIIa may also help to improve haemostasis in other
      situations involving impaired thrombin generation, such as platelet disorders
      (thrombocytopenia and functional platelet defects). Preliminary clinical data
      appear to support this. Patients with profuse bleeding due to extensive surgery
      or trauma often develop a complex coagulation pattern which includes reduced
      plasma levels of fibrinogen, FVIII and FV, and decreased platelet counts. These
      patients may well have an impaired capacity to generate thrombin. Consequently,
      they may benefit from one or two doses of rFVIIa in order to assist in the
      generation of a thrombin peak sufficient to form a firm, stable fibrin
      haemostatic plug and thereby reduce bleeding. This would facilitate any
      mechanical repair necessary for full haemostasis. Preliminary results in a few
      patients may support such an effect for rFVIIa. As thrombin has such a crucial
      role in providing haemostasis, any agent that enhances the thrombin generation in
      situations with an impaired thrombin formation may be characterised as a 'general
      haemostatic agent'. Let us look forward to more 'facts' through the 'evidence
      based route'.

PMID- 12214146
TI  - Treatment of bleeding in patients with platelet disorders: is there a place for
      recombinant factor VIIa?
AB  - The mechanism of action of recombinant factor VIIa (rFVIIa), i.e. increased
      thrombin generation on the membrane of activated platelets, as well as the
      results from in vitro and ex vivo models of thrombocytopenia or inherited
      thrombocytopathia may support some potential of rFVIIa in
      thrombocytopenia/thrombocytopathia. rFVIIa was reported as effective to stop or
      to decrease bleeding in few patients with severe thrombocytopenia resistant to
      platelet transfusions; however data are still scarce and clinical studies are
      really needed to define efficacy/safety ratio as well as optimal treatment
      regimen in this potential indication. Some data in patients with Glanzmann
      thrombasthenia (GT) may support the use of rFVIIa outside its primary indication
      in the cases in which there is no real treatment alternative (GT patients with
      antibodies to GP IIb-IIIa or with platelet refractoriness).

PMID- 12214147
TI  - The use of recombinant factor VIIa in controlling surgical bleeding in non
      haemophiliac patients.
AB  - Recombinant factor VIIa (rFVIIa, NovoSeven) is effective and appears safe in the
      management of bleeding episodes and provision of surgical cover in haemophilia
      patients with inhibitors. Additionally, rFVIIa has been considered as a universal
      haemostatic agent, prompting its use in the management of severe uncontrolled
      surgical bleeding in patients without pre-existing coagulopathies. Recombinant
      FVIIa has been used in 5 patients (aged 2.5 to 73.0 years; median 48 years) with
      uncontrolled bleeding during or after open-heart surgery. Satisfactory
      haemostasis was achieved with a single dose or rFVIIa 30 microg/kg, that resulted
      in reduction of blood loss from a mean of 4,170 ml (650-8,000 ml) to 262.5 ml
      (220-334 ml). No significant adverse events were reported. Recombinant FVIIa was
      also successfully used in controlling post-surgical bleeding in two patients with
      Crohn's disease, one patient with bleeding duodenal ulcer and another with false
      thoracic aneurysm. It was also effective in controlling bleeding post-splenectomy
      in a patient with chronic myeloid leukaemia, and following anterior exenteration
      in a patient with cervical carcinoma. A randomised study comparing the efficacy
      of a single perioperative dose of rFVIIa with placebo in patients undergoing
      transabdominal prostatectomy was conducted by Levi and colleagues [6]. An interim
      analysis showed a significant reduction in mean blood loss from 2,450 +/- 350 ml
      to 1,400 +/- 190 ml between placebo and rFVIIa groups respectively (p = 0.007).
      Among trauma patients, Kenet et al. reported success in treating uncontrolled
      bleeding from a gun-shot wound to the inferior vena cava, using two doses of
      rFVIIa 60 microg/kg [7]. This treatment has subsequently been used in 6 surgical
      patients with uncontrolled bleeding and in 7 cases of traumatic bleeding, with
      remarkable results. In conclusion, rFVIIa appears to be effective and safe in the
      management of uncontrolled surgical and traumatic haemorrhage in patients not
      known to have inherited coagulopathy.

PMID- 12214148
TI  - To general haemostasis--the evidence-based route.
AB  - Recombinant factor VIIa (rFVIIa) was developed for the treatment of bleeding in
      haemophilia patients with inhibitors and has also been used successfully in non
      haemophilia patients with acquired antibodies against FVIII (acquired
      haemophilia). Based on dose-finding trials and a compassionate-use programme,
      rFVIIa was approved for use in haemophilia patients with inhibitors in 1996. At
      pharmacological doses, rFVIIa has been found to enhance thrombin generation on
      already activated platelets. Therefore, it is likely that rFVIIa will also be
      beneficial in providing haemostasis in other situations characterised by profuse
      bleedings and an impaired thrombin generation. Patients with thrombocytopenia
      have a decreased number of platelets and thus an impaired thrombin generation. A
      reduction in bleeding time was reported in approximately 50% of patients with
      thrombocytopenia and a prolonged bleeding time who participated in a trial of
      rFVIIa. Moreover, in 8 patients with 9 overt bleeds who were involved in the
      study, bleeding stopped in 7 episodes after rFVIIa administration. Case reports
      on the haemostatic effect of rFVIIa in thrombocytopenia have also been published.
      Reports have also been published on the successful use of rFVIIa in patients with
      platelet function deficiencies such as Glanzmann's thrombasthenia and Bernard
      Soulier syndrome. A number of haemostatic changes occur after extensive trauma,
      surgery and bleeding, all of which potentially contribute to an impaired thrombin
      generation. The effect of rFVIIa has been demonstrated in a number of patients
      after trauma and bleeds and upper gastrointestinal bleeding episodes. Reports on
      the beneficial use of rFVIIa in liver transplantation have also been published.
      Several randomised blinded studies are now underway in e.g. hepatectomy, upper
      gastrointestinal bleedings, transplantations and intra-cerebral bleeds. In
      summary, rFVIIa may be an effective and safe method to induce haemostasis in
      patients within areas of coagulation factor deficiency or platelet disorders and
      the ongoing and planned randomised studies may lead the way to the use of rFVIIa
      in general haemostasis.

PMID- 12214149
TI  - Common C677T polymorphism of the methylenetetrahydrofolate reductase gene and the
      risk of venous thromboembolism: meta-analysis of 31 studies.
AB  - BACKGROUND: Although the common 677 C --> T polymorphism of the
      methylenetetrahydrofolate reductase (MTHFR) gene is implicated in the development
      of hyperhomocysteinemia, its correlation with venous thromboembolism (VTE)
      remains controversial. We conducted a meta-analysis of previously published
      studies to clarify the role of the MTHFR 677 TT homozygous genotype in
      association with VTE. METHODS AND RESULTS: Relevant articles were retrieved from
      a systematic search of Medline and Embase from 1990 to September 2001. Two
      independent reviewers abstracted data on the characteristics of the cases with
      VTE and controls without VTE. We pooled the rates of the MTHFR 677 TT genotype in
      both groups, as well as the odds ratio (OR) of VTE in the presence of the TT
      versus CC or CT genotypes. In 31 published studies, comprising 4,901 cases and
      7,886 controls, the pooled prevalence of the MTHFR 677 TT genotype was slightly
      higher among cases (14.3%) than controls (11.7%), conferring a borderline degree
      of heightened risk [pooled OR (OR(p)) 1.2, 95% confidence interval (CI) 1.1-1.4].
      After excluding cases with a classic thrombophilia factor, the pooled prevalence
      rates of the MTHFR 677 TT genotype among 11 studies were 17.7 and 12.3%,
      respectively (OR(p) 1.5, 95% CI 1.2-1.9). CONCLUSIONS: The classic MTHFR C677T
      gene polymorphism is weakly associated with an increased risk of VTE. It is
      unlikely that the purported relationship between hyperhomocysteinemia and VTE is
      mediated by this gene defect to a substantial degree, although other undiscovered
      gene polymorphisms may explain this association. Until more compelling data are
      made available, we do not recommend that testing for the MTHFR C677T polymorphism
      be routinely included as part of any clinical thrombophilia assessment.

PMID- 12214150
TI  - Home treatment of deep vein thrombosis. An out-patient treatment model with once
      daily injection of low-molecular-weight heparin (tinzaparin) in 555 patients.
AB  - During a 22-month period, 555 consecutive patients at seven hospitals in the
      western part of Sweden with an acute deep vein thrombosis (DVT) not involving the
      iliac vein and not having pulmonary embolism were included in a study testing the
      efficacy of implementing out-patient treatment. For all patients with a confirmed
      diagnosis of acute DVT, a folder was used that contained two checklists with
      detailed instructions for further treatment, one for the doctor and one for the
      nurse, an information pamphlet for the patient and prepared prescriptions for low
      molecular-weight heparin (LMWH) tinzaparin (Innohep) of 175 anti-Xa IU/kg body
      weight subcutaneously once daily and warfarin. Patients not requiring
      hospitalisation, according to strict guidelines, were then eligible for treatment
      as out-patients. Prior to release from the emergency department for home
      treatment, a nurse provided detailed information to the patient and administered
      the first tinzaparin injection. In 194 (35.0%) out of 555 patients, the DVT was
      localised only in the lower leg not reaching the popliteal vein. Factors
      predisposing to venous thromboembolism were identified in 35.0% of the patients.
      332 (59.8%) out of the 555 patients studied did not require hospitalisation and
      were therefore treated as out-patients. 140 of these patients (42.2%) injected
      themselves, the injection was given by a relative in 63 (19.0%) patients and by
      the community nurse in 129 (38.9%). Six (1.8%) patients reported a worsening of
      the DVT condition during the LMWH treatment period. No major bleedings were
      observed during the injection treatment period. Except for local minor skin
      bleedings at the injection site, only 3 (0.9%) patients reported minor bleedings
      during the injection treatment period. Recurrences of venous thromboembolism
      during the first 2 months were reported in 9 patients (2.7%) out of 332 patients
      who were sent home from the emergency department. Five (2.2%) patients out of the
      223 who were admitted to the hospital had an increased tendency to bleeding.
      Twelve patients (5.4%) were hospitalised because of a pronounced local status, 26
      (11.7%) were senile, social factors were the reason for hospitalisation in 76
      (34.1%) and lack of time of the physician in 39 (17.5%) of the patients. A
      pharmacoeconomic analysis found a cost reduction of 69% with the present model
      for home treatment compared with traditional in-hospital treatment of DVT
      patients. We conclude that tinzaparin can be safely used at home by patients with
      DVT below the inguinal region and that the model used in the present study is
      cost-effective.

PMID- 12214152
TI  - Screening for cancer in patients with idiopathic venous thromboembolism: the
      clinical practice.
AB  - The reported incidence of concomitant cancer in patients with idiopathic venous
      thromboembolism (IVTE) varies between 4 and 24%, while the mean incidence of
      cancer within 3 years thereafter approximates 9%. Baseline investigations of
      patients with IVTE have been recommended. We evaluated the clinical practice
      regarding the screening of these patients according to these recommendations in
      two teaching hospitals. Medical history and physical examination were done
      reasonably exhaustively, except for investigations of the urogenital tract.
      Laboratory and imaging investigations were performed incompletely in a
      substantial proportion of the patients. The clinical evaluation regarding cancer,
      performed in patients with IVTE, could be improved. The implementation of a
      protocol should be considered.

PMID- 12214151
TI  - Effects of a long-term pharmacological interruption of the renin-angiotensin
      system on the fibrinolytic system in essential hypertension.
AB  - To assess the effects of pharmacological interruption of the renin-angiotensin
      system on the fibrinolysis, tissue plasminogen activator antigen (t-PA),
      plasminogen activator inhibitor-1 antigens (PAI-1) and neurohormones, such as
      plasma renin activity, norepinephrine, angiotensin II (AII) and IV (AIV)
      concentrations, were measured in 60 hypertensives. Among them, 48 patients were
      divided into two groups (25 with 10-20 mg quinapril and 23 with 50-100 mg
      losartan) who received the drug for 6 months. AII had a weak positive correlation
      with free PAI-I (n = 60, r = 0.26, p < 0.05) whereas AIV had a strong positive
      correlation with free PAI-I (n = 60, r = 0.57, p < 0.0001). In both treatment
      groups, blood pressures were significantly reduced to similar levels after drug
      treatment. While plasma renin activity increased significantly in both groups
      after drug treatment, only the losartan group showed significant increases in AII
      and AIV concentrations. In the quinapril group, there was a significant change in
      t-PA (p < 0.001) without changes in PAI-1. In the losartan group, free PAI-I and
      total PAI-I (p < 0.05 for free PAI-I and p < 0.04 for total PAI-I) were
      significantly increased without a change in t-PA. Thus, quinapril enhanced
      fibrinolysis but losartan attenuated it. These unique effects of each drug on the
      fibrinolytic system appear to be associated with changes in AII and AIV
      concentrations.

PMID- 12214153
TI  - Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 levels
      in acute myocardial infarction.
AB  - The cause of the circadian variation in the incidence of acute myocardial
      infarction (AMI) has not been identified. Tissue plasminogen activator (t-PA) and
      plasminogen activator inhibitor-1 (PAI-1) have opposing effects on thrombi.
      Hence, the extent of the clot, the size of the infarct and outcome of patients
      could depend on t-PA and PAI-1 levels. In an effort to elucidate the
      pathophysiologic basis of circadian variation of AMI, we investigated the
      presence of a possible corresponding circadian variation in the levels of
      endogenous t-PA and PAI-1 in patients diagnosed to have AMI and the effects of
      hypertension, diabetes and site of the infarct on these levels. We estimated the
      levels of t-PA and PAI-1 in platelet-poor plasma of 42 patients with AMI on
      admission, using the enzyme-linked immunosorbant assay. Although not
      statistically significant, patients having an AMI in the morning hours had the
      highest t-PA:PAI-1 ratio. The normal circadian variation in PAI-1 levels was lost
      in patients with AMI, probably due to the disease process. Also, the t-PA levels
      in hypertensive patients were significantly lower than in nonhypertensives. PAI-1
      levels were also significantly lower in patients with anteroseptal than in
      inferior and anterolateral AMI. This relationship between the fibrinolytic
      potential and the site of infarction needs further study. Furthermore, t-PA
      levels on admission were significantly lower in survivors and may have a
      predictive value in determining the outcome.

PMID- 12214154
TI  - Modulation of Bcl-2 family proteins in primary endothelial cells during
      apoptosis.
AB  - We studied the expression of Bcl-2 family proteins during cytokine- and verotoxin
      (VT)-induced apoptosis in primary human umbilical vein endothelial cells
      (HUVECs). Our experiments demonstrated that high initial expression of Bcl-2
      protein was significantly downregulated in HUVECs treated with IFN-gamma whereas
      TNF-alpha gave a less pronounced decrease in Bcl-2 level. Treatment with the
      combination of cytokines was more efficient in downregulating Bcl-2 protein.
      HUVECs pretreated with cytokines and incubated with VT gave a further significant
      decrease in Bcl-2 level. Simultaneous measurement of Bcl-xl level did not reveal
      any significant changes. Bax protein was upregulated in HUVECs stimulated with
      TNF-alpha alone or in combination with IFN-gamma. However, addition of VT did not
      give any further increase in Bax level suggesting that Bax upregulation is more
      important for cytokine- rather than VT-mediated apoptosis. Total endothelial cell
      growth factor deprivation gave a significant increase in apoptosis accompanied by
      a decrease of Bcl-2 in apoptotic cells while Bcl-xl and Bax levels were
      unaffected. Our data indicate that anti-apoptotic protein Bcl-2 and pro-apoptotic
      protein Bax are reciprocally regulated during apoptosis, whilst Bcl-xl is
      essentially unaffected. This implies that Bcl-2/Bax ratio rather than Bcl-xl
      controls apoptosis in primary endothelial cells.

PMID- 12214155
TI  - Platelets and anticoagulant capacity in patients with inflammatory bowel disease.
AB  - Patients with inflammatory bowel disease (IBD) are susceptible to thromboembolic
      complications. Several mechanisms can be responsible, including abnormal
      regulation of coagulation activity, disturbances of fibrinolysis, inflammatory
      reactions and thrombocytosis. The aim of this study was to assess hemostatic
      alterations in these parameters during exacerbation of disease. We studied
      disease activity in 99 IBD patients receiving anti-inflammatory therapy, in
      relation to: procoagulant markers, i.e. prothrombin fragment F1 + 2 (F1 + 2), D
      dimer and platelet count, anticoagulant markers, i.e. protein C, protein S and
      antithrombin, and a mediator of inflammation (IL-6). Coagulation activity and
      platelet count were increased during active disease in IBD patients compared with
      those in a state of remission. The IL-6 concentrations were positively correlated
      with disease activity and thrombocytosis in patients with ulcerative colitis, but
      no association with the anticoagulant capacity could be demonstrated except for a
      decrease in protein C during high disease activity.

PMID- 12214157
TI  - Resistance to activated protein C, factor V leiden and the prothrombin G20210A
      variant in patients with colorectal cancer.
AB  - OBJECTIVE: The aim of our study was to determine the frequency of resistance to
      activated protein C (APC), factor V Leiden (FVL) and the prothrombin G20210A
      variant in patients with colorectal cancer. METHODS: 74 patients with colorectal
      cancer and 192 colonoscopically selected controls were prospectively investigated
      for the presence of APC resistance, FVL and the prothrombin G20210A variant. APC
      resistance was measured as the ratio of activated partial thromboplastin times
      with and without APC (APC sensitivity ratio, APC-SR). The FVL and prothrombin
      G20210A variant were detected by a polymerase-chain-reaction-based technique.
      RESULTS: FVL was detected in the heterozygous form in 4 of 74 cancer patients
      (5.4%) and in 7 of 192 controls (3.6%; p > 0.5, odds ratio: 1.51). After
      excluding patients and controls with FVL, APC-SR was below 2 in 6 of 70 cancer
      patients (8.5%) and in 1 of 185 controls (0.5%; p < 0.01, odds ratio: 17.25), and
      the mean value of APC-SR was significantly lower in cancer patients than the
      respective level of controls (2.8 vs. 3.7, p < 0.001). The G20210A mutation in
      the prothrombin gene was found in the heterozygous form in 2 of 74 patients with
      colorectal cancer (2.7%) and in 5 of 192 colonoscopically control subjects (2.6%;
      p > 0.5, odds ratio: 1.03). CONCLUSIONS: These findings suggest that patients
      with colorectal cancer have a high frequency of resistance to APC but no
      significant differences in the frequency of the FVL or G20210A mutation of the
      prothrombin gene compared to colonoscopically selected controls.

PMID- 12214158
TI  - Failure of platelet parameters and biomarkers to correlate platelet function to
      severity and etiology of heart failure in patients enrolled in the EPCOT trial.
      With special reference to the Hemodyne hemostatic analyzer. Whole Blood Impedance
      Aggregometry for the Assessment of Platelet Function in Patients with Congestive
      Heart Failure.
AB  - Data from small studies have suggested the presence of platelet abnormalities in
      patients with congestive heart failure (CHF). We sought to characterize the
      diagnostic utility of different platelet parameters and platelet-endothelial
      biomarkers in a random outpatient CHF population investigated in the EPCOT
      ('Whole Blood Impedance Aggregometry for the Assessment of Platelet Function in
      Patients with Congestive Heart Failure') Trial. Blood samples were obtained for
      measurement of platelet contractile force (PCF), whole blood aggregation, shear
      induced closure time, expression of glycoprotein (GP) IIb/IIIa, and P-selectin in
      100 consecutive patients with CHF. Substantial interindividual variability of
      platelet characteristics exists in patients with CHF. There were no statistically
      significant differences when patients were grouped according to incidence of
      vascular events, emergency revascularization needs, survival, or etiology of
      heart failure. Aspirin use did not affect instrument readings either. PCF
      correlates very poorly with whole blood aggregometry (r(2) = 0.023), closure time
      (r(2) = 0.028), platelet GP IIb/IIIa (r(2) = 0.0028), and P-selectin (r(2) =
      0.002) expression. Furthermore, there was no correlation with brain natriuretic
      peptide concentrations, a marker of severity and prognosis in heart failure
      reflecting the neurohumoral status. Patients with heart failure enrolled in the
      EPCOT Trial exhibited a marginal, sometimes oppositely directed change in
      platelet function, challenging the diagnostic utility of these platelet
      parameters and biomarkers to serve as useful tools for the identification of
      platelet abnormalities, for predicting clinical outcomes, or for monitoring
      antiplatelet strategies in this population. The usefulness of these measurements
      for assessing platelets in the different clinical settings remains to be
      explored. Taken together, opposite to our expectations, major clinical
      characteristics of heart failure did not correlate well with the platelet
      characteristics investigated in this study.

PMID- 12214159
TI  - Effects of aspirin and clopidogrel versus oral anticoagulation on platelet
      function and on coagulation in patients with nonvalvular atrial fibrillation
      (CLAFIB).
AB  - The aim of the study was to evaluate the effect of two antithrombotic therapies
      on platelet function and on coagulation in patients with nonvalvular atrial
      fibrillation (NVAF). Twenty patients with NVAF were treated with aspirin (300
      mg/day) and clopidogrel (75 mg/day) for 2 weeks immediately followed by oral
      anticoagulation (target international normalized ratio 2.0-3.0). Parameters of
      platelet function and coagulation were evaluated before antithrombotic therapy,
      at the end of aspirin plus clopidogrel and during subsequent anticoagulation
      treatment. Aspirin plus clopidogrel significantly inhibited platelet aggregation,
      fibrinogen receptor activation and release of P-selectin and prolonged in vitro
      bleeding time (p < 0.01). Coagulation parameters (platelet-dependent thrombin
      generation, antithrombin III, thrombin-antithrombin III complex, prothrombin
      fragment 1 + 2) were not significantly affected. During the subsequent oral
      anticoagulation phase platelet function was not substantially reduced; however,
      coagulation parameters were significantly inhibited (p < 0.001). The results
      indicate that combined antiplatelet therapy is superior to aspirin monotherapy in
      inhibiting platelet function but does not seem to substantially modulate
      coagulation cascade in patients with NVAF.

PMID- 12214160
TI  - Nitric oxide-cGMP and prostacyclin-cAMP pathways in patients with type II
      diabetes and different types of retinopathy.
AB  - The aim of this study was to investigate two factors of endothelial dysfunction
      and their platelet second messengers in patients with type II diabetes and
      different types of retinopathy. We compared 20 healthy volunteers and 117
      patients with type II diabetes (34 with no signs of diabetic retinopathy, 26 with
      background diabetic retinopathy, 29 with ischemic-proliferative diabetic
      retinopathy and 28 with edematous diabetic retinopathy). The following parameters
      were recorded: platelet aggregometry, nitrites, 6-keto-prostaglandin-F(1alpha)
      and intraplatelet cAMP and cGMP. Platelet aggregation was greater in patients
      with diabetic retinopathy. The concentration of ADP that produced 50% maximum
      intensity of aggregation was 1.81 microM in patients without diabetic
      retinopathy, 0.92 microM in patients with background diabetic retinopathy, 0.85
      microM in patients with ischemic-proliferative diabetic retinopathy and 0.44
      microM in patients with edematous diabetic retinopathy. The platelets in these
      patients were more resistant to inhibition by SIN-1 (concentrations of SIN-1 that
      produced 50% inhibition of maximum intensity of collagen-induced aggregation in
      the four patient groups: 18.1, 13.6, 16.2 and 33.2 microM, respectively). Nitrite
      concentration in patients with ischemic-proliferative diabetic retinopathy was
      one sixth of the value in healthy controls, but there was no significant
      difference between the control group and patients with edematous diabetic
      retinopathy. In the latter group, neutrophils increased nitrite production by
      68.7 +/- 3%, whereas in patients with ischemic-proliferative diabetic
      retinopathy, this increase was 18.7 +/- 2.0%. We conclude that nitric oxide
      production is higher in patients with type II diabetes and edematous retinopathy
      than in those with ischemic-proliferative retinopathy. This finding, together
      with the possibly greater production of free radicals, may explain the greater
      impairment of platelet function in the former patients.

PMID- 12214161
TI  - Low-dosage intravenous immunoglobulin in the management of a patient with
      acquired von Willebrand syndrome associated with monoclonal gammopathy of
      undetermined significance.
AB  - We report herein the case of a 69-year-old Japanese man with acquired von
      Willebrand syndrome associated with monoclonal gammopathy of undetermined
      significance who developed IgG1-kappa antibodies against von Willebrand factor
      (VWF). The patient was urged to undergo tooth extractions because of alveolar
      pyorrhea, and a low-dosage intravenous immunoglobulin (IV-Ig) therapy (0.3 g of
      IgG/kg/day for 3 days) was chosen for him. On the 4th day after the infusion, VWF
      antigen and VWF ristocetin cofactor increased to 40 and 78% of the control,
      respectively, and dental extractions were performed successfully. On the 7th day,
      these values reached a maximum, i.e. 95 and 160% of the control, respectively.
      Then, they quickly decreased to 35 and 75% on the 10th day, and 6 months later,
      they became 16 and <3% of the control, respectively. Upon analysis of plasma VWF
      multimers (VWFMs) in this patient, those with large to medium molecular masses
      more selectively disappeared before the IV-Ig infusion than did those with small
      molecular masses. On the 4th day, the pattern of VWFMs was completely normalized
      and appeared to persist until the 10th day. Six months later, a small amount of
      large to medium-sized VWFMs was still present, but at 7-8 months, the pattern of
      VWFMs became almost the same as that before infusion. Throughout the patient's
      clinical course, the activity of plasma VWF-cleaving protease, which specifically
      cleaves the Tyr842-Met843 bond of the subunit and reduces its multimeric sizes,
      was quite normal (95-119%). These results provided consistent evidence that the
      selective absence of VWFMs with large to medium molecular masses in this patient
      is caused by the heightened clearance of a complex of IgG inhibitor and VWFMs
      from the circulation, presumably through IgG binding to the Fc receptor of
      macrophages. Furthermore, these results also indicated that a low-dosage IV-Ig
      therapy is effective enough for hemostatic management for programmed surgery.

PMID- 12214162
TI  - Effects of the Magenstrasse and Mill operation for obesity on plasma plasminogen
      activator inhibitor type 1, tissue plasminogen activator, fibrinogen and insulin.
AB  - Plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (t-PA),
      fibrinogen and insulin were measured in 43 patients 3 years after they had
      undergone the Magenstrasse and Mill (MM) procedure and in 43 morbidly obese (MO)
      patients. Mean plasma PAI-1 was 61 ng/ml in the MO group compared to 30 ng/ml in
      the MM group (p < 0.0001); mean plasma t-PA was 10 ng/ml in the MO group compared
      to 7 ng/ml in the MM group (p < 0.001). Mean fibrinogen was 3.6 g/l in the MO
      group compared to 3.2 g/l in the MM group (p < 0.05). Mean plasma insulin levels
      were 32 U/ml in the MO group compared to 15 U/ml in the MM group. These changes
      suggest that use of the MM procedure may reduce mortality and morbidity from
      coronary heart disease in these high-risk obese patients.

PMID- 12214163
TI  - Isolation of endogenous anticoagulant N-sulfated glycosaminoglycans in human
      plasma from healthy subjects.
AB  - Endogenous N-sulfated glycosaminoglycans (GAGs) comigrating with standard heparin
      and sensitive to nitrous acid treatment were isolated from plasma of healthy
      donors. The amount of these compounds was 7-10 microg/ml, and activated partial
      thromboplastin time, anti-Xa and anti-IIa activities were similar to those of
      standard heparin of high molecular mass. Analysis with gradient PAGE of the
      putative endogenous heparin showed a mean molecular mass of 12 kD. These N
      sulfated GAGs could be isolated only after removal of binding peptides that
      impaired purification by ion-exchange chromatography. We used SDS-PAGE as a tool
      to separate peptides from endogenous GAGs. N-sulfated GAGs exited the gel before
      peptides when the electrophoresis was overrun. Endogenous GAGs could be recovered
      by ion-exchange chromatography of the SDS-PAGE buffer, 'free' from associating
      peptides. These results strongly support the hypothesis that endogenous heparin
      is associated in vitro with a variety of proteins and that this association could
      be responsible for modification of both heparin and protein activities.

PMID- 12214164
TI  - Management of heart failure in the elderly: still much to be learned.

PMID- 12214165
TI  - Heart failure in the elderly: undertreated or understudied?

PMID- 12214166
TI  - Patterns of ACE inhibitor use in elderly medicaid patients with heart failure.
AB  - The authors identified 321 elderly Kansas Medicaid patients with congestive heart
      failure and examined angiotensin-converting enzyme (ACE) inhibitor use. Using
      retrospective claims data, ACE inhibitor use was quantified and daily doses
      compared to a target enalapril-equivalent dose of 20 mg. The cohort patients
      averaged 80 years of age, 84% were female, and 70% resided primarily in a nursing
      home. Only 37.8% received an ACE inhibitor. Users were younger than nonusers
      (t=2.00; p=0.046), but there was no gender difference (odds ratio [OR], 1.4; 95%
      confidence interval [CI], 0.73, 2.6). ACE inhibitor users averaged eight
      prescriptions annually, providing approximately 257 medication days (70% of the
      study period). The average enalapril-equivalent daily dose was 10.6 mg, and only
      22% received the target dose. Nursing home residents were less likely to receive
      an ACE inhibitor than ambulatory patients (OR, 0.55; 95% CI, 0.34, 0.89) but
      equally likely to receive target doses (OR, 1.3; 95% CI, 0.34, 4.9). ACE
      inhibitor use in the Kansas Medicaid congestive heart failure population is not
      consistent with practice guidelines, particularly among older and/or nursing home
      patients.

PMID- 12214167
TI  - Aortic pulse wave velocity: an independent marker of cardiovascular risk.
AB  - Aortic pulse wave velocity, a classic index of aortic stiffness, may be easily
      measured in humans using noninvasive ultrasound methods of high reproducibility.
      Recent epidemiologic studies have shown that, independently of confounding
      factors such as age, blood pressure and cardiac mass, aortic pulse wave velocity
      is a predictor of cardiovascular mortality in populations of hypertensive
      subjects, whether they have end-stage renal disease or not. Since aortic pulse
      wave velocity is dominantly influenced by age, this finding may be of major
      importance for the evaluation of cardiovascular risk in geriatric populations.

PMID- 12214168
TI  - Reversal of heart failure remodeling with age.
AB  - Since heart failure is a major cause of morbidity in the elderly, we studied the
      effect of up-titrated heart failure therapy in older vs. younger individuals on
      symptoms and left ventricular (LV) function over 1 year. Seventy-one patients
      with heart failure and an LV ejection fraction < or =35% were enrolled and were
      followed with echocardiography at baseline and at 1 year. Young patients were
      born in or after 1935 (n=48; 51.7+/-9.1 years); middle-aged were born between
      1925-1934 (n=14; 69.7+/-2.8 years); and older patients in or prior to 1924 (n=9;
      80.5+/-3.3 years). Baseline LV ejection fraction was 18%+/-7%, LV end-diastolic
      diameter 6.9+/-0.9 cm, and New York Heart Association class was 2.6+/-1.0,
      equivalent for all groups. On medical therapy, at 12 months, LV ejection fraction
      improved only for the young and middle-aged (36%+/-14% and 37%+/-17%; p=0.002),
      but not for the older patients (22%+/-7%; p=NS). Reductions in LV end-diastolic
      diameter and mitral regurgitation were significant only for the young. However,
      New York Heart Association status improved similarly for all groups (1.6+/-0.8;
      p<0.001), as did heart failure hospitalizations (p<0.0001). Although all groups
      tolerated intensified heart failure therapy, only the young and middle-aged
      improved LV remodeling. However, older patients experienced equivalent
      significant improvements in heart failure symptoms and hospitalizations.

PMID- 12214169
TI  - Pacing therapy in the elderly.
AB  - Bradycardia due to sinus node dysfunction and atrioventricular block is more
      commonly observed in the elderly. Aging is associated with progressive fibrosis
      in both the sinus node and atrioventricular conduction system (AV node, His
      bundle, right and left bundles). In the absence of reversible causes implantation
      of a permanent pacemaker is often required in the patient with symptomatic
      bradycardia. For elderly patients with sinus node dysfunction, pacing modes that
      preserve atrioventricular synchrony are associated with a reduced incidence of
      atrial fibrillation and improved quality of life. For patients with
      atrioventricular block, the importance of preserving atrioventricular synchrony
      in the elderly is controversial and is currently being evaluated.

PMID- 12214170
TI  - Clinical profile of chronic heart failure in elderly women.
AB  - The pathogenesis, clinical course, and treatment of chronic heart failure (HF)
      are different in elderly women from those of patients recruited in the landmark
      trials of chronic HF. Patients included in these landmark trials were
      predominantly men whose age was 10-15 years younger than the average age of
      patients with chronic HF in the United States. Diastolic dysfunction resulting in
      impaired left ventricular (LV) filling is the preponderant LV functional
      alteration that leads to chronic HF in elderly women. Gender differences in the
      LV remodeling process that accompanies chronic cardiac pressure are likely to be
      responsible for the preponderance of LV diastolic dysfunction over systolic
      dysfunction in elderly women. In response to chronic pressure overload, the LV
      wall becomes thicker in women than in men. Consequently, in response to chronic
      pressure overload, women are able to normalize LV wall stress and preserve LV
      systolic function to a greater extent than men. However, impaired LV filling is
      an undesirable consequence of the greater increase in LV wall thickness in women.
      Thus, clinical observations and therapeutic guidelines derived from data
      collected in the landmark trials of chronic HF may not apply to elderly women
      with chronic HF. In view of the lack of evidence-based information needed to
      guide the management of elderly women with chronic HF, special attention should
      be given to include a substantial number of elderly women in future therapeutic
      trials recruiting patients with chronic HF.

PMID- 12214171
TI  - Ethical issues in the management of geriatric cardiac patients: a patient asks to
      put an end to the nightmare of living with a lifesaving AICD.

PMID- 12214172
TI  - A-V junctional rhythm with P following QRS.

PMID- 12214173
TI  - Transesophageal three-dimensional echocardiographic demonstration of clefts in
      the anterior tricuspid valve leaflet.

PMID- 12214174
TI  - Invasive vs. conservative management of acute coronary syndromes in the elderly.

PMID- 12214175
TI  - HOPE in PROGRESS--a tale of two trials: blood pressure reduction or drug
      mechanism?

PMID- 12214185
TI  - Barriers to expanding primary care roles for chiropractors: The role of
      chiropractic as primary care gatekeeper.
AB  - OBJECTIVE: To examine the feasibility of broader and more frequent primary care
      roles for chiropractors. DATA COLLECTION: Literature review and analysis of
      existing databases. Six types of barriers were examined, including legal,
      financial, professional, accessibility or geographic location, consumer
      preference, and self-imposed barriers. RESULTS: Although research into the
      barriers of an expanded primary care role for chiropractors is inconclusive,
      several inferences can be drawn from this analysis. First, prevailing state
      practice acts preclude only a limited number of activities that are necessary for
      chiropractors to serve in a primary care capacity. The self-perception by a
      portion of the chiropractic profession that as neuromusculoskeletal system
      specialists, they are either uninterested or ill-prepared for providing primary
      care serves as a second barrier. Third, payment provisions that do not permit
      chiropractors to be reimbursed for primary care services significantly limit
      their ability to expand primary care capacity. Fourth, consumer perceptions of
      chiropractors as neuromusculoskeletal system specialists are a persistent barrier
      to expanding status. Given the current importance of managed care, the fifth and
      most crucial barrier for chiropractic may be managed care organizations' lack of
      interest in having chiropractors in primary care roles. CONCLUSION: Research on
      the barriers to a more expanded primary care role for chiropractors is
      incomplete. The available research helps little in ruling out plausible barriers
      that might make it possible to narrow the scope of subsequent research.

PMID- 12214186
TI  - Can patient reactions to the first chiropractic treatment predict early favorable
      treatment outcome in persistent low back pain?
AB  - OBJECTIVE: To investigate whether 3 distinct patterns of reactions to
      chiropractic care predict early favorable treatment outcome in patients with
      persistent low back pain. DESIGN AND SETTING: Multicenter, clinic-based
      prospective outcome study with standardized interview questionnaires conducted in
      private chiropractic practices in Sweden. STUDY SUBJECTS: Previously compliant
      chiropractors were invited to participate in the study. A maximum of 20
      consecutive patients (per chiropractor) who sought chiropractic care for low back
      pain with or without sciatica with a duration of more than 2 weeks at the time of
      consultation and for a minimum of 30 days total during the past year.
      INTERVENTION: Chiropractic management as decided by the treating chiropractor.
      OUTCOME AND PREDICTOR VARIABLES: Improvement was defined at the 4th visit as self
      reported "definitely improved" (the best of 5 choices). The hypothesized most
      favorable prognostic group had immediate improvement reported on the 1st visit,
      reduced pain intensity reported on the 2nd visit, reduced disability reported on
      the 2nd visit, and a common reaction or no reaction reported on the 2nd visit.
      The hypothesized least favorable prognostic group had no immediate improvement on
      the 1st visit, no reduction of pain intensity on the 2nd visit, no reduced
      disability on the 2nd visit, and no reaction or an uncommon reaction reported on
      the 2nd visit. The hypothesized intermediate prognostic group included all
      patients who did not fit into the hypothesized most favorable or least favorable
      groups. COVARIABLES: Age, sex, pain intensity during past 24 hours, description
      of disability, duration and pattern of pain during present attack, duration and
      pattern of pain during past 12 months. ANALYSIS OF DATA: The 3 predictor-groups
      were cross-tabulated against the outcome variable and the other covariates.
      RESULTS: Of the 115 patients in the most favorable prognostic group, 84% (95%
      confidence interval, 77-91) reported to be "definitely improved" by the 4th visit
      versus 63% (59-67) of the 384 patients in the intermediate prognostic group, and
      30% (22-38) of the 116 patients in the least favorable prognostic group. No major
      interactions from the covariates could explain these results. CONCLUSION: Among
      chiropractic patients with persistent low back pain, it is possible to predict
      which patients will report definite improvement early in the course of treatment.

PMID- 12214187
TI  - The effect of Trager therapy on the level of evoked stretch responses in patients
      with Parkinson's disease and rigidity.
AB  - OBJECTIVE: To quantify changes of evoked stretch responses (ESR) in the most
      rigid arm of patients with Parkinson's disease (PD) after Trager therapy.
      METHODS: Gentle rocking motion associated with this type of manual therapy was
      imparted to the upper limbs and body of 30 patients for 20 minutes. A pretest and
      2 posttests (at 1 and 11 minutes after the treatment, respectively) were
      performed, consisting of electromyographic (EMG) recordings of the flexor carpi
      radialis and extensor digitorum communis while the patient's wrist was passively
      flexed and extended with an amplitude of 60 degrees and a frequency of 1 Hz.
      Patients received the treatment on the most rigid side of their bodies (ipsi
      group) or on the contralateral side (contra-group). Half of patients in each
      group received the treatment while lying supine on a massage table (ipsi- and
      contra-supine) or sitting in a chair (ipsi- and contra-sitting). RESULTS: In
      general, the level of ESR were reduced by 36% immediately after treatment and
      remained 32% lower than pretest values 11 minutes after treatment (F = 41.45, P
      <.05). Patients who received the treatment lying supine benefited from a 42%
      reduction of ESR (F = 4.07, P <.05). The side on which the treatment was
      performed did not significantly influence the outcome of the treatment (F = 0.50,
      P >.05). However, post hoc analysis of the triple interaction (test x side x
      position) indicated that the sitting position was much less efficient for
      sustained contralateral effect (P >.05). CONCLUSIONS: Results from the present
      study strongly suggest that it is possible to modify the level of ESR by using
      Trager therapy. This stretch reflex inhibition may induce a reduction of the
      muscle rigidity seen in these patients. The present results may eventually lead
      to the development of a specific complementary therapy for patients with
      Parkinson's disease and rigidity.

PMID- 12214188
TI  - Immediate changes in the quadriceps femoris angle after insertion of an orthotic
      device.
AB  - OBJECTIVE: To measure changes in the quadriceps femoris angle (Q-angle) after the
      insertion of full-length flexible orthotics. SETTING: Outpatient health center of
      Logan College of Chiropractic. SUBJECTS: A total of 40 male subjects were
      included in the study population. The selected population all demonstrated
      bilateral pes planus or hyperpronation syndrome. DESIGN: Before-after trial.
      METHOD: A cohort demonstrating bilateral hyperpronation was recruited. The
      subjects were cast according to standard protocols provided by the manufacturer.
      Subject right and left Q-angles were measured with and without the orthotic in
      place. The landmarks used were marked with a permanent marker, and great care was
      taken to accurately assess the angles formed. The evaluator was not told whether
      the measure was before or after orthotic insertion. A modified quailcraft
      goniometer was used. DATA ANALYSIS: The data set was collected and assessed by
      the t test. RESULTS: Thirty-nine of 40 test subjects showed reduced Q-angle,
      which was in the direction of correction. A 2-tailed matched sample showed
      statistically significant mean reduction in Q-angle measures. There was a
      minority of patients who showed asymmetrical Q-angle measures. Within this group
      there was greater symmetry of Q-angle measures after placement of the orthotic.
      CONCLUSION: Insertion of full-length, flexible orthotic devices significantly
      improves the Q-angle in hyperpronating male subjects. If the literature
      accurately links an increase in the Q-angle with a predisposition for knee
      injury, then the possibility of long-term benefits following the use of flexible
      orthotics exists. More research is required to determine whether these
      biomechanical changes are maintained after use of these orthotics.

PMID- 12214189
TI  - Uneventful upper cervical manipulation in the presence of a damaged vertebral
      artery.
AB  - OBJECTIVE: To discuss a case in which a patient with a previously injured
      vertebral artery underwent manipulation in the upper cervical spine without
      alteration of her symptom pattern. The literature concerning the relative safety
      of specific upper cervical manipulative techniques is reviewed. CLINICAL
      FEATURES: A 42-year-old woman had a 3-week history of unilateral suboccipital
      pain that she related to a sudden twisting of her head and neck that occurred
      while she was putting sheets of drywall on top of her car. Subsequent examination
      by a neurologist 2 weeks later was unremarkable, and a tension-type headache was
      diagnosed. Approximately 10 days later (3 weeks after injury), a single high
      velocity upper-cervical manipulation (incorporating slight rotation and full
      lateral flexion) was performed with no change in her symptom pattern. Two weeks
      after that, the patient had development of a lateral medullary syndrome (also
      known as Wallenberg syndrome) after she briefly extended and rotated her upper
      cervical spine while painting a ceiling. INTERVENTION AND OUTCOME: The patient
      was treated with anticoagulant therapy, and the lateral medullary infarct healed
      without incident. The spinocerebellar and subtle motor symptoms also resolved,
      but the ipsilateral suboccipital headache and the loss of temperature sensation
      associated with the spinothalamic tract lesion were still present 9 months later.
      CONCLUSION: This case report demonstrates that vigorous manipulation of the upper
      cervical spine is possible without injuring an already damaged vertebral artery.
      It is suggested that the line of drive used during the single manipulation,
      almost pure lateral flexion with slight rotation, was responsible for the
      apparent innocuous response. Guidelines for the evaluation and management of
      vertebral artery dissection are reviewed. Because it is currently impossible to
      identify patients at risk of having a dissected vertebral artery with standard in
      office examination procedures, rotational manipulation of the upper cervical
      spine should be abandoned by all practitioners, and schools should remove such
      techniques from their curriculums.

PMID- 12214190
TI  - The kinematics of motion palpation and its effect on the reliability for cervical
      spine rotation.
AB  - BACKGROUND: The reliability of a test depends on its standardization.
      Instrumental measurement of the reproducibility of the test is an effective way
      to evaluate the level of standardization obtained. Improved standardization is
      believed to yield greater reliability. OBJECTIVE: The objectives of this study
      were to measure the technical ability of an examiner to reproduce the kinematics
      of motion palpation for cervical spine rotation and to evaluate the effect of
      standardization on the reliability of the test. DESIGN: A study of
      reproducibility of the kinematics of the test for cervical spine rotation was
      conducted by means of a computerized system of analysis of movement. The
      reliability when reproducibility was achieved was compared with reliability when
      it failed. RESULTS: The data collected enable us to establish a standardized
      protocol for the execution of the test. The standardized palpation is executed
      within 6 of inclination from the pure plane of rotation. The successful
      reproduction of the kinematics of the test raises its reliability to detect the
      presence of fixations (kappa raising from 0.337 and 0.352 to 0.682). CONCLUSIONS:
      A greater reliability, arising from a high level of reproducibility, enables us
      to document the advantages of the standardization of motion palpation in
      chiropractic.

PMID- 12214191
TI  - Obstacles to biodefence.

PMID- 12214192
TI  - Geneticists lay foundations for human transcriptome database.

PMID- 12214193
TI  - Bush urged to boost funding for physical sciences.

PMID- 12214196
TI  - Dispute over first authorship lands researchers in dock.

PMID- 12214195
TI  - Name-calling gets stem-cell researcher into hot water.

PMID- 12214197
TI  - Court judgement opens door for study of ancient skeleton.

PMID- 12214198
TI  - Diabetes trial stirs debate on safety of xenotransplants.

PMID- 12214199
TI  - Working your way into industry.

PMID- 12214200
TI  - Hunt for cosmic rays offers scope for Africa.

PMID- 12214201
TI  - Norway sinks ocean carbon study.

PMID- 12214202
TI  - Call for cash to end the decay of Berlin's great collections.

PMID- 12214203
TI  - Gene-bank expansion plan launched at Earth summit.

PMID- 12214207
TI  - Let's catch some rays.

PMID- 12214206
TI  - Mission impossible?

PMID- 12214208
TI  - French users need European neutrons.

PMID- 12214209
TI  - Shared knowledge can combat malaria.

PMID- 12214210
TI  - Prokaryote taxonomy online: challenges ahead.

PMID- 12214215
TI  - A chemical compass.

PMID- 12214216
TI  - RNA as drug and antidote.

PMID- 12214217
TI  - The matter with antimatter.

PMID- 12214219
TI  - Cell biology: spinning actin to divide.

PMID- 12214220
TI  - Edge effects.

PMID- 12214221
TI  - Immunology: the roots of antibody diversity.

PMID- 12214222
TI  - Stressed to quaking point.

PMID- 12214223
TI  - A lost Neanderthal neonate found.
AB  - Fossil remains of adult Neanderthals are well documented, but juvenile specimens
      are rare and information about them is scant. Here we identify a beautifully
      preserved skeleton that has been lost to science for almost 90 years as the
      Neanderthal neonate known as 'Le Moustier 2', which was originally found at Le
      Moustier in the Dordogne, southwest France. This find will be a rich source of
      data for studying the evolution of human ontogeny as well as the phylogenetic
      relationship between these extinct hominids and anatomically modern humans.

PMID- 12214224
TI  - Effect of British hunting ban on fox numbers.
AB  - Pressure to ban the hunting of foxes with hounds in Britain has fuelled debate
      about its contribution to the control of fox populations. We took advantage of a
      nationwide one-year ban on fox-hunting during the outbreak of foot-and-mouth
      disease (FMD) in 2001 to examine this issue and found that the ban had no
      measurable impact on fox numbers in randomly selected areas. Our results argue
      against suggestions that fox populations would increase markedly in the event of
      a permanent ban on hunting.

PMID- 12214225
TI  - The voltage-gated potassium channels and their relatives.
AB  - The voltage-gated potassium channels are the prototypical members of a family of
      membrane signalling proteins. These protein-based machines have pores that pass
      millions of ions per second across the membrane with astonishing selectivity, and
      their gates snap open and shut in milliseconds as they sense changes in voltage
      or ligand concentration. The architectural modules and functional components of
      these sophisticated signalling molecules are becoming clear, but some important
      links remain to be elucidated.

PMID- 12214226
TI  - Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA
      glycosylase.
AB  - A functional immune system depends on the production of a wide range of
      immunoglobulin molecules. Immunoglobulin variable region (IgV) genes are
      diversified after gene rearrangement by hypermutation. In the DNA deamination
      model, we have proposed that deamination of dC residues to dU by activation
      induced deaminase (AID) triggers this diversification. In hypermutating chicken
      DT40 B cells, most IgV mutations are dC --> dG/dA or dG --> dC/dT transversions,
      which are proposed to result from replication over sites of base loss produced by
      the excision activity of uracil-DNA glycosylase. Blocking the activity of uracil
      DNA glycosylase should instead lead to replication over the dU lesion, resulting
      in dC --> dT (and dG --> dA) transitions. Here we show that expression in DT40
      cells of a bacteriophage-encoded protein that inhibits uracil-DNA glycosylase
      shifts the pattern of IgV gene mutations from transversion dominance to
      transition dominance. This is good evidence that antibody diversification
      involves dC --> dU deamination within the immunoglobulin locus itself.

PMID- 12214227
TI  - Spin vector alignment of Koronis family asteroids.
AB  - Studies of asteroid families--groups of asteroids that formed from the
      fragmentation of larger bodies--are of broad interest to solar system researchers
      because they can provide insights into collisional processes, as well as the
      interior structures, strengths, and compositions of asteroids. It is generally
      accepted that members of the Koronis family were created by collisional
      disruption of a homogeneous parent body and therefore share the same formation
      age and subsequent collisional history. The temporal variations in observed
      brightness of the Koronis family members (a consequence of their rotation) are,
      however, larger than expected. Preferential alignment of spin vectors had been
      proposed as a possible explanation, but recent modelling predicted that family
      formation yields random spin vectors among the resulting fragments. Both
      hypotheses have been untested by observations. Here I show that the actual
      distribution of spin vectors among the largest members of the Koronis family
      falls within markedly nonrandom 'spin clusters'. Reconciling models of family
      formation and evolution with the unexpected alignments of spin obliquity and
      correlations with spin rates presents a new challenge in understanding asteroid
      collisional processes.

PMID- 12214228
TI  - Collapse and revival of the matter wave field of a Bose-Einstein condensate.
AB  - A Bose-Einstein condensate represents the most 'classical' form of a matter wave,
      just as an optical laser emits the most classical form of an electromagnetic
      wave. Nevertheless, the matter wave field has a quantized structure owing to the
      granularity of the discrete underlying atoms. Although such a field is usually
      assumed to be intrinsically stable (apart from incoherent loss processes), this
      is no longer true when the condensate is in a coherent superposition of different
      atom number states. For example, in a Bose-Einstein condensate confined by a
      three-dimensional optical lattice, each potential well can be prepared in a
      coherent superposition of different atom number states, with constant relative
      phases between neighbouring lattice sites. It is then natural to ask how the
      individual matter wave fields and their relative phases evolve. Here we use such
      a set-up to investigate these questions experimentally, observing that the matter
      wave field of the Bose-Einstein condensate undergoes a periodic series of
      collapses and revivals; this behaviour is directly demonstrated in the dynamical
      evolution of the multiple matter wave interference pattern. We attribute the
      oscillations to the quantized structure of the matter wave field and the
      collisions between individual atoms.

PMID- 12214229
TI  - The structure and chemistry of the TiO(2)-rich surface of SrTiO(3) (001).
AB  - Oxide surfaces are important for applications in catalysis and thin film growth.
      An important frontier in solid-state inorganic chemistry is the prediction of the
      surface structure of an oxide. Comparatively little is known about atomic
      arrangements at oxide surfaces at present, and there has been considerable
      discussion concerning the forces that control such arrangements. For instance,
      one model suggests that the dominant factor is a reduction of Coulomb forces;
      another favours minimization of 'dangling bonds' by charge transfer to states
      below the Fermi energy. The surface structure and properties of SrTiO(3)--a
      standard model for oxides with a perovskite structure--have been studied
      extensively. Here we report a solution of the 2 x 1 SrTiO(3) (001) surface
      structure obtained through a combination of high-resolution electron microscopy
      and theoretical direct methods. Our results indicate that surface rearrangement
      of TiO(6-x) units into edge-sharing blocks determines the SrO-deficient surface
      structure of SrTiO(3). We suggest that this structural concept can be extended to
      perovskite surfaces in general.

PMID- 12214230
TI  - Evidence from the AD 2000 Izu islands earthquake swarm that stressing rate
      governs seismicity.
AB  - Magma intrusions and eruptions commonly produce abrupt changes in seismicity far
      from magma conduits that cannot be associated with the diffusion of pore fluids
      or heat. Such 'swarm' seismicity also migrates with time, and often exhibits a
      'dog-bone'-shaped distribution. The largest earthquakes in swarms produce
      aftershocks that obey an Omori-type (exponential) temporal decay, but the
      duration of the aftershock sequences is drastically reduced, relative to normal
      earthquake activity. Here we use one of the most energetic swarms ever recorded
      to study the dependence of these properties on the stress imparted by a magma
      intrusion. A 1,000-fold increase in seismicity rate and a 1,000-fold decrease in
      aftershock duration occurred during the two-month-long dyke intrusion. We find
      that the seismicity rate is proportional to the calculated stressing rate, and
      that the duration of aftershock sequences is inversely proportional to the
      stressing rate. This behaviour is in accord with a laboratory-based rate/state
      constitutive law, suggesting an explanation for the occurrence of earthquake
      swarms. Any sustained increase in stressing rate--whether due to an intrusion,
      extrusion or creep event--should produce such seismological behaviour.

PMID- 12214231
TI  - Pretender punishment induced by chemical signalling in a queenless ant.
AB  - Animal societies are stages for both conflict and cooperation. Reproduction is
      often monopolized by one or a few individuals who behave aggressively to prevent
      subordinates from reproducing (for example, naked mole-rats, wasps and ants).
      Here we report an unusual mechanism by which the dominant individual maintains
      reproductive control. In the queenless ant Dinoponera quadriceps, only the alpha
      female reproduces. If the alpha is challenged by another female she chemically
      marks the pretender who is then punished by low-ranking females. This cooperation
      between alpha and low-rankers allows the alpha to inflict punishment indirectly,
      thereby maintaining her reproductive primacy without having to fight.

PMID- 12214232
TI  - An ultra-sparse code underlies the generation of neural sequences in a songbird.
AB  - Sequences of motor activity are encoded in many vertebrate brains by complex
      spatio-temporal patterns of neural activity; however, the neural circuit
      mechanisms underlying the generation of these pre-motor patterns are poorly
      understood. In songbirds, one prominent site of pre-motor activity is the
      forebrain robust nucleus of the archistriatum (RA), which generates stereotyped
      sequences of spike bursts during song and recapitulates these sequences during
      sleep. We show that the stereotyped sequences in RA are driven from nucleus HVC
      (high vocal centre), the principal pre-motor input to RA. Recordings of
      identified HVC neurons in sleeping and singing birds show that individual HVC
      neurons projecting onto RA neurons produce bursts sparsely, at a single, precise
      time during the RA sequence. These HVC neurons burst sequentially with respect to
      one another. We suggest that at each time in the RA sequence, the ensemble of
      active RA neurons is driven by a subpopulation of RA-projecting HVC neurons that
      is active only at that time. As a population, these HVC neurons may form an
      explicit representation of time in the sequence. Such a sparse representation, a
      temporal analogue of the 'grandmother cell' concept for object recognition,
      eliminates the problem of temporal interference during sequence generation and
      learning attributed to more distributed representations.

PMID- 12214233
TI  - Deficient pheromone responses in mice lacking a cluster of vomeronasal receptor
      genes.
AB  - The mammalian vomeronasal organ (VNO), a part of the olfactory system, detects
      pheromones--chemical signals that modulate social and reproductive behaviours.
      But the molecular receptors in the VNO that detect these chemosensory stimuli
      remain undefined. Candidate pheromone receptors are encoded by two distinct and
      complex superfamilies of genes, V1r and V2r (refs 3 and 4), which code for
      receptors with seven transmembrane domains. These genes are selectively expressed
      in sensory neurons of the VNO. However, there is at present no functional
      evidence for a role of these genes in pheromone responses. Here, using chromosome
      engineering technology, we delete in the germ line of mice an approximately 600
      kilobase genomic region that contains a cluster of 16 intact V1r genes. These
      genes comprise two of the 12 described V1r gene families, and represent
      approximately 12% of the V1r repertoire. The mutant mice display deficits in a
      subset of VNO-dependent behaviours: the expression of male sexual behaviour and
      maternal aggression is substantially altered. Electrophysiologically, the
      epithelium of the VNO of such mice does not respond detectably to specific
      pheromonal ligands. The behavioural impairment and chemosensory deficit support a
      role of V1r receptors as pheromone receptors.

PMID- 12214234
TI  - The ELF4 gene controls circadian rhythms and flowering time in Arabidopsis
      thaliana.
AB  - Many plants use day length as an environmental cue to ensure proper timing of the
      switch from vegetative to reproductive growth. Day-length sensing involves an
      interaction between the relative length of day and night, and endogenous rhythms
      that are controlled by the plant circadian clock. Thus, plants with defects in
      circadian regulation cannot properly regulate the timing of the floral
      transition. Here we describe the gene EARLY FLOWERING 4 (ELF4), which is involved
      in photoperiod perception and circadian regulation. ELF4 promotes clock accuracy
      and is required for sustained rhythms in the absence of daily light/dark cycles.
      elf4 mutants show attenuated expression of CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), a
      gene that is thought to function as a central oscillator component. In addition,
      elf4 plants transiently show output rhythms with highly variable period lengths
      before becoming arrhythmic. Mutations in elf4 result in early flowering in non
      inductive photoperiods, which is probably caused by elevated amounts of CONSTANS
      (CO), a gene that promotes floral induction.

PMID- 12214236
TI  - Actin dynamics in the contractile ring during cytokinesis in fission yeast.
AB  - Cytokinesis in many eukaryotes requires a contractile ring of actin and myosin
      that cleaves the cell in two. Little is known about how actin filaments and other
      components assemble into this ring structure and generate force. Here we show
      that the contractile ring in the fission yeast Schizosaccharomyces pombe is an
      active site of actin assembly. This actin polymerization activity requires Arp3,
      the formin Cdc12, profilin and WASP, but not myosin II or IQGAP proteins. Both
      newly polymerized actin filaments and pre-existing actin cables can contribute to
      the initial assembly of the ring. Once formed, the ring remains a dynamic
      structure in which actin and other ring components continuously assemble and
      disassemble from the ring every minute. The rate of actin polymerization can
      influence the rate of cleavage. Thus, actin polymerization driven by the Arp2/3
      complex and formins is a central process in cytokinesis. Our studies show that
      cytokinesis is a more dynamic process than previously thought and provide a
      perspective on the mechanism of cell division.

PMID- 12214235
TI  - Protective role of phospholipid oxidation products in endotoxin-induced tissue
      damage.
AB  - Lipopolysaccharide (LPS), an outer-membrane component of Gram-negative bacteria,
      interacts with LPS-binding protein and CD14, which present LPS to toll-like
      receptor 4 (refs 1, 2), which activates inflammatory gene expression through
      nuclear factor kappa B (NF kappa B) and mitogen-activated protein-kinase
      signalling. Antibacterial defence involves activation of neutrophils that
      generate reactive oxygen species capable of killing bacteria; therefore host
      lipid peroxidation occurs, initiated by enzymes such as NADPH oxidase and
      myeloperoxidase. Oxidized phospholipids are pro-inflammatory agonists promoting
      chronic inflammation in atherosclerosis; however, recent data suggest that they
      can inhibit expression of inflammatory adhesion molecules. Here we show that
      oxidized phospholipids inhibit LPS-induced but not tumour-necrosis factor-alpha
      induced or interleukin-1 beta-induced NF kappa B-mediated upregulation of
      inflammatory genes, by blocking the interaction of LPS with LPS-binding protein
      and CD14. Moreover, in LPS-injected mice, oxidized phospholipids inhibited
      inflammation and protected mice from lethal endotoxin shock. Thus, in severe Gram
      negative bacterial infection, endogenously formed oxidized phospholipids may
      function as a negative feedback to blunt innate immune responses. Furthermore,
      identified chemical structures capable of inhibiting the effects of endotoxins
      such as LPS could be used for the development of new drugs for treatment of
      sepsis.

PMID- 12214237
TI  - The U1 snRNP protein U1C recognizes the 5' splice site in the absence of base
      pairing.
AB  - Splicing of precursor messenger RNA takes place in the spliceosome, a large
      RNA/protein macromolecular machine. Spliceosome assembly occurs in an ordered
      pathway in vitro and is conserved between yeast and mammalian systems. The
      earliest step is commitment complex formation in yeast or E complex formation in
      mammals, which engages the pre-mRNA in the splicing pathway and involves
      interactions between U1 small nuclear ribonucleoprotein (snRNP) and the pre-mRNA
      5' splice site. Complex formation depends on highly conserved base pairing
      between the 5' splice site and the 5' end of U1 snRNA, both in vivo and in vitro.
      U1 snRNP proteins also contribute to U1 snRNP activity. Here we show that U1
      snRNP lacking the 5' end of its snRNA retains 5'-splice-site sequence
      specificity. We also show that recombinant yeast U1C protein, a U1 snRNP protein,
      selects a 5'-splice-site-like sequence in which the first four nucleotides, GUAU,
      are identical to the first four nucleotides of the yeast 5'-splice-site consensus
      sequence. We propose that a U1C 5'-splice-site interaction precedes pre-mRNA/U1
      snRNA base pairing and is the earliest step in the splicing pathway.

PMID- 12214238
TI  - RNA aptamers as reversible antagonists of coagulation factor IXa.
AB  - Many therapeutic agents are associated with adverse effects in patients.
      Anticoagulants can engender acute complications such as significant bleeding that
      increases patient morbidity and mortality. Antidote control provides the safest
      means to regulate drug action. For this reason, despite its known limitations and
      toxicities, heparin use remains high because it is the only anticoagulant that
      can be controlled by an antidote, the polypeptide protamine. To date, no
      generalizable strategy for developing drug-antidote pairs has been described. We
      investigated whether drug-antidote pairs could be rationally designed by taking
      advantage of properties inherent to nucleic acids to make antidote-controlled
      anticoagulant agents. Here we show that protein-binding oligonucleotides
      (aptamers) against coagulation factor IXa are potent anticoagulants. We also show
      that oligonucleotides complementary to these aptamers can act as antidotes
      capable of efficiently reversing the activity of these new anticoagulants in
      plasma from healthy volunteers and from patients who cannot tolerate heparin.
      This generalizable strategy for rationally designing a drug-antidote pair thus
      opens up the way for developing safer regulatable therapeutics.

PMID- 12214242
TI  - Introduction. Centrosome.

PMID- 12214243
TI  - Centrosome amplification and the development of cancer.

PMID- 12214244
TI  - Two for two: Cdk2 and its role in centrosome doubling.

PMID- 12214245
TI  - Centrosomes and checkpoints: the MPS1 family of kinases.

PMID- 12214246
TI  - The role of nucleophosmin in centrosome duplication.
AB  - In higher animal cells, duplication of centrosomes is triggered by CDK2/cyclin E
      mediated phosphorylation. Nucleophosmin (NPM)/B23, a multifunctional protein, has
      recently been identified as one of the substrates of CDK2/cyclin E in centrosome
      duplication. Centrosome-bound NPM/B23 dissociates from centrosome upon
      phosphorylation by CDK2/cyclin E, which in turn triggers initiation of centriole
      duplication. Duplicated centrosomes remain free of NPM/B23 till mitosis. When the
      nuclear membrane breaks down during mitosis, NPM/B23 re-localizes to centrosomes.
      Upon cytokinesis, each daughter cell receives one centrosome bound by NPM/B23,
      which again dissociates from the centrosome upon exposure to CDK2/cyclin E at mid
      late G1 phase of the next cell cycle. Thus, NPM/B23 would constitute one of the
      licensing systems for centrosome duplication, ensuring the coordination of
      centrosome and DNA duplication, which limiting duplication once per cell cycle.

PMID- 12214248
TI  - The Nek2 protein kinase: a novel regulator of centrosome structure.
AB  - Regulation of the centrosome, the major microtubule organizing centre in an
      animal cell, is in large part controlled by cell cycle-dependent protein
      phosphorylation. Along with cyclin dependent kinases, polo kinases and Aurora
      kinases, NIMA-related kinases are emerging as critical regulators of centrosome
      structure and function. Nek2 is the most closely related vertebrate protein by
      sequence to the essential mitotic regulator NIMA of Aspergillus nidulans. Nek2 is
      highly enriched at the centrosome and functional studies in human and Xenopus
      systems support a role for Nek2 in both maintenance and modulation of centrosome
      architecture. In particular, current evidence supports a model in which one
      function of Nek2 kinase activity is to promote the splitting of duplicated
      centrosomes at the onset of mitosis through phosphorylation of core centriolar
      proteins. Recent studies in lower organisms have raised the possibility that
      kinases related to Nek2 may have conserved functions in MTOC organization, as
      well as in other aspects of mitotic progression.

PMID- 12214247
TI  - On the role of aurora-A in centrosome function.
AB  - Mammalian aurora-A belongs to a multigenic family of mitotic serine/threonine
      kinases comprising two other members: aurora-B and aurora-C. In this review we
      will focus on aurora-A that starts to localize to centrosomes only in S phase as
      soon as centrioles have been duplicated, the protein is then degraded in early
      G1. Works in various organisms have revealed that the kinase is involved in
      centrosome separation, duplication and maturation as well as in bipolar spindle
      assembly and stability. Aurora kinases are found in all organisms in which their
      function has been conserved throughout evolution, namely the control of
      chromosome segregation. In human, aurora-A has focused a lot of attention, since
      its overexpression has been found to be correlated with the grade of various
      solid tumours. Ectopic kinase overexpression in any culture cell line leads to
      polyploidy and centrosome amplification. However, overexpression of aurora-A in
      particular cell lines such as NIH3T3 is sufficient to induce growth on soft agar.
      Those transformed cells form tumours when implanted in immunodeficient mice,
      indicating that the kinase is an oncogene.

PMID- 12214249
TI  - Polo-like kinases and centrosome regulation.

PMID- 12214250
TI  - The ZYG-1 kinase, a mitotic and meiotic regulator of centriole replication.

PMID- 12214251
TI  - Control of the centriole and centrosome cycles by ubiquitination enzymes.

PMID- 12214252
TI  - Roles of BRCA1 in centrosome duplication.
AB  - Centrosome duplication is under precise control and occurs only once in a normal
      mammalian cell cycle. Disruption of this process causes centrosome amplification,
      unequal segregation of chromosomes and, ultimately, tumorigenesis. Recent studies
      indicate that breast cancer suppressor gene 1 (BRCA1) plays an important role in
      regulating centrosome duplication. BRCA1 is located in the centrosome and binds
      to gamma-tubulin. It interacts with a variety of proteins that regulate
      centrosome duplication, including BRCA2, CDK2-Cyclin A, CDK2-Cyclin E, Gadd45,
      p21, p53 and Rb. Furthermore, targeted disruption of murine BRCA1 results in
      centrosome amplification, suggesting that BRCA1 serves as a negative regulator
      for centrosome duplication. This review will examine these data and discuss
      possible relationships between BRCA1 and its interacting proteins in centrosome
      duplication.

PMID- 12214253
TI  - Genomic instability, centrosome amplification, cell cycle checkpoints and
      Gadd45a.
AB  - Genomic instability has been a recognized feature of many human tumors for
      decades. Until recently, however, there was little insight into potential
      mechanisms for this phenomenon. Recent work has shown first, that increased
      centrosome numbers (also referred to as centrosome amplification) often accompany
      genomic instability and second, that when centrosome numbers are increased, cells
      become genetically unstable. Deletion of Gadd45a leads to centrosome
      amplification and consequent abnormal mitosis and aneuploidy. Gadd45a is known to
      be involved in a G2 checkpoint and may be involved in the normal progression from
      G2 to M and its coordination with S phase events. Whether these functions
      contribute to prevention of centrosome amplification is being investigated.
      However, potential mechanisms can be proposed based on known protein associations
      with Gadd45a, as well as proteins that regulate Gadd45a transcription and are
      also required for efficient coordination of centrosome duplication and DNA
      synthesis.

PMID- 12214254
TI  - Loss of p53 and centrosome hyperamplification.
AB  - Loss or mutational inactivation of p53 has been shown to lead to abnormal
      amplification of centrosomes through deregulation of the centrosome duplication
      cycle and failure to undergo cytokinesis. In mouse cells, most cases of
      centrosome hyperamplification are attributed to deregulation of centrosome
      duplication. The presence of excess copies of centrosomes increases the frequency
      of mitotic defects, leading to unbalanced chromosome transmission to daughter
      cells. p53 controls centrosome duplication via transactivation-dependent and
      transactivation-independent mechanisms. In its transactivation-dependent control,
      p21(Waf1/Cip1) acts as a major effector, likely guarding against untimely
      activation of CDK2/cyclin E kinase, hence ensuring the coordinated initiation of
      centrosome and DNA duplication. p53 appears to exert its transactivation
      independent control through direct physical binding to the centrosomes.

PMID- 12214255
TI  - Human papillomaviruses and centrosome duplication errors: modeling the origins of
      genomic instability.
AB  - The majority of human cancers are genomically unstable, often with gains or
      losses of whole chromosomes. In high-risk human papillomavirus (HPV)-associated
      cervical neoplasia, the two HPV-encoded oncoproteins E6 and E7 have been
      implicated in mitotic infidelity by their ability to induce centrosome-related
      mitotic disturbances. However, the mechanisms by which HPV E6 and E7 subvert
      centrosome homeostasis are strikingly different. Whereas the E7 oncoprotein
      rapidly drives centrosome duplication errors in cells that appear phenotypically
      normal, expression of the HPV E6 oncoprotein results in an accumulation of
      supernumerary centrosomes in multinucleated cells. The primary centrosome
      duplication defect in HPV E7 expressing cells may be linked to the ability of E7
      to disrupt regulatory nodes that govern both the host cell division cycle
      machinery and the initiation of centrosome duplication. Most importantly, the E7
      oncoprotein has been shown to dysregulate cdk2 activity, a major determinant for
      the initiation of centrosome duplication. HPV-induced centrosome abnormalities,
      multipolar mitoses, and aneuploidy often occur at early stages during cervical
      carcinogenesis and increase with malignant conversion. These findings suggest
      that HPV oncoprotein-induced chromosomal instability increases the risk for
      genetic changes that may ultimately facilitate carcinogenic progression.

PMID- 12214256
TI  - Pulse pressure and coronary mortality in elderly men and women from general
      population.
AB  - The aim of this work was to evaluate whether pulse pressure (PP) in elderly
      people is a better predictor of coronary mortality than systolic and diastolic
      blood pressure taken alone. For this aim, 3282 elderly subjects aged >or=65 years
      were studied in a population-based frame. Blood pressure was repeatedly measured
      and averaged; historical data, anthropometrics, blood tests and 14-year coronary
      mortality were recorded. Statistics included analysis of covariance, Cox analysis
      and bivariate vectorial analysis. Coronary mortality in women was predicted by PP
      (1.01 excess risk/mm Hg PP) and was significantly higher in the 3rd than in the
      1st tertile of PP (relative risk 2.90); neither systolic nor diastolic pressure
      taken alone influenced mortality. When systolic and diastolic pressures were both
      entered into a Cox model, the former had a positive and the latter a negative
      effect on survival, confirming a prognostic role of PP. For any given level of
      systolic pressure, mortality was inversely associated with diastolic pressure.
      Finally, the mean vector representing both systolic and diastolic pressures of
      non-surviving women was characterised by higher systolic and lower diastolic
      components than in non-surviving. No significant trend of mortality in relation
      to either systolic blood pressure or PP was observed in men. In conclusion, the
      combination of systolic and diastolic pressure called PP is an independent
      predictor of coronary mortality in elderly females, and a better predictor than
      systolic or diastolic pressure alone.

PMID- 12214257
TI  - A randomised controlled trial of the effect of anticipation of a blood test on
      blood pressure.
AB  - Blood pressure is affected by situational anxiety, such as the white coat effect.
      We hypothesised that blood pressure would also be affected by anticipation of a
      blood test. Volunteer subjects were recruited on the campus of Birmingham
      University. Subjects were randomly assigned to intervention and control groups.
      After a period of rest, three seated blood pressure measurements were taken at 1
      min intervals using an electronic sphygmomanometer. Between the second and third
      measurements subjects in the intervention group were told that a blood test would
      be carried out after the last measurement. No blood test was carried out. Three
      blood pressure measurements were made in all 213 randomised subjects. Analysis
      was by intention-to-treat. In the control group mean systolic and diastolic blood
      pressure fell in successive measurements. Between the second and third
      measurements mean systolic blood pressure fell by 1.4 mm Hg in the control group
      and rose by 2.6 mm Hg in the intervention group (difference 4.0 mm Hg, P <
      0.0001). A rise in diastolic blood pressure between the second and third
      measurements did not reach statistical significance. It was concluded that
      anticipation of a blood test affects measured systolic blood pressure in
      volunteers. The practice of taking blood tests at the same time as measuring
      blood pressure may potentially bias estimations of blood pressure.

PMID- 12214258
TI  - Evolution of ambulatory measurement of blood pressure and parameters of arterial
      stiffness over a 1-year period in patients with systemic sclerosis: ERAMS study.
AB  - Patients with systemic sclerosis commonly exhibit increased arterial stiffness,
      which may be predictive of the overall severity of the disease. The aim of the
      present study was to check the stability of parameters of arterial stiffness
      after 1 year in this population. ERAMS is a French multicentric prospective study
      designed to identify a link between arterial distensibility and outcome in 100
      patients with systemic sclerosis. Arterial distensibility was evaluated by 24-h
      ambulatory monitoring of QKD interval along with blood pressure (BP) and heart
      rate (HR) (four measurements/hour). The index QKD(100-60), which is linked to
      aortic distensibility, was calculated automatically. QKD(100-60) is the value of
      QKD (which depends on pulse wave velocity) for 100 mm Hg sBP and 60 bpm HR. The
      reproducibility of QKD(100-60) was assessed on the first patients to be followed
      up for a complete year. So far the 100 patients have been recruited from 14
      participating centres and 48 were re-evaluated after 1 year. QKD(100-60) was
      highly reproducible: 201 +/- 6 vs202 +/- 18 msec, standard deviation of
      difference = 13 msec. IN CONCLUSION: determination of QKD(100-60) to assess
      arterial stiffness gives stable results over 1 year in patients with systemic
      sclerosis.

PMID- 12214259
TI  - Diuretic induced hyponatraemia in elderly hypertensive women.
AB  - Diuretics are recommended as first-line antihypertensive treatment in elderly
      patients. Although attention is usually paid to prevent hypokalaemia with
      diuretic therapy, risk of hyponatraemia is often ignored. We performed this study
      to characterise hypertensive patients at increased risk to develop hyponatraemia.
      We reviewed charts of hypertensive patients hospitalised in Chaim Sheba Medical
      Center for hyponatraemia from 1990 to 1997. Patients with other causes of
      hyponatraemia were excluded. The General Practice Maccabi database was used to
      estimate age and sex distribution of patients prescribed diuretics for
      hypertension. We identified 180 hypertensive patients (149 F, 31 M; mean age 76.4
      +/- 9.2 years) hospitalised because of hyponatraemia. Across all age groups, odds
      ratio (OR) to develop hyponatraemia was three times higher for women vs men (OR
      3.10, 95% confidence interval (CI): 2.07-4.67). One hundred and sixty-two
      patients (90%) were older than 65 years. Patients of both sexes older than 65
      years were 10 times (and if they were older than 75 years 16 times) more likely
      to develop hyponatraemia than those younger than 65 years (OR 9.87, 95%, CI: 5.93
      16.64). Most patients (74.5%) used a thiazide-based diuretic; only 10% used a low
      dose (<25 mg/day). In 37% of patients diuretics were used for more than 1 year
      before hyponatraemia developed. Diuretic-induced hyponatraemia may be insidious
      and appear even after prolonged diuretics use. Elderly women seem to be at
      particularly high risk. In this population diuretic use should be associated with
      close monitoring of sodium and potassium levels.

PMID- 12214260
TI  - The -174 G/C polymorphism of the interleukin-6 gene promoter and essential
      hypertension in an elderly Italian population.
AB  - Several studies have proposed a relationship between blood pressure and
      inflammation. Interleukin-6 (IL-6) is a multifunctional cytokine involved in
      inflammation and tissue injury and potentially influencing blood pressure.
      Recently, a common polymorphism of the IL-6 gene, associated with differences in
      the transcription rate of the protein, has been described. The aim of this study
      was to investigate a possible association between genetic variations of the 
      174GC polymorphism of the IL-6 gene promoter and hypertension in humans. IL-6
      gene promoter polymorphism was evaluated by polymerase chain reaction followed by
      restriction enzyme analysis in 210 elderly Italian patients affected by essential
      hypertension (EH) and 177 age- and sex-matched controls. The distribution of IL-6
      genotypes was 85 GG, 88 GC, 37 CC in the hypertensive patients and 65 GG, 73 GC,
      39 CC in the control subjects. In this elderly cohort, no statistically
      significant association was found between the two groups (P = 0.45 for GG
      homozygous, P = 0.89 for GC heterozygous and P = 0.27 for CC homozygous). In
      conclusion the -174 GC polymorphism of the IL-6 gene promoter is not a marker for
      EH in this sample of elderly Italians.

PMID- 12214261
TI  - Relationship between transforming growth factor beta1 and progression of
      hypertensive renal disease.
AB  - In this study the role of circulating transforming growth factor beta1 (TGFbeta1)
      on progression of renal hypertensive disease has been investigated. Fifty
      consecutive outpatients with essential hypertension were enrolled and divided
      into three groups, according to their urinary albumin excretion (UAE). Group A
      comprised 10 hypertensives with UAE <or=20 mg/24 h (normoalbuminuric group);
      Group B included 21 hypertensives with UAE > 20 < 300 mg/24 h (microalbuminuric
      group); Group C encompassed 19 hypertensives with UAE >or= 300 mg/24 h
      (proteinuric group). In all patients UAE by immunonephelometric assay,
      circulating TGFbeta1 by a solid phase specific sandwich ELISA technique, BUN and
      creatinine by routine laboratory methods were determined. In addition, left
      ventricular telediastolic internal diameter, interventricular septum diastolic
      (IVSTd), posterior wall thickness, total and normalised to height(2.7) left
      ventricular mass, relative wall thickness and left ventricular ejection fraction
      by M-B Mode echocardiography were calculated. Our results indicated that TGFbeta1
      levels were significantly (P < 0.05) higher in Group B and C than Group A and in
      Group C than Group B. In addition IVSTd values were significantly (P < 0.05)
      higher in both Group B and C than Group A. An evident, but not significant,
      higher prevalence of subjects with left ventricular hypertrophy were observed in
      Group C as compared with other groups. In all hypertensive subjects TGFbeta1
      correlated directly with UAE (P < 0.0001) but not with BMI, LVM/h(2.7) and mean
      blood pressure. Our data indicated that TGFbeta1 might be considered a useful
      marker to evaluate the severity and progression of hypertensive renal disease.
      Additional long-term clinical data are needed to evaluate whether inhibition of
      TGFbeta1 system may prolong the time to the ESRD in hypertensive patients.

PMID- 12214262
TI  - Accuracy of the Dinamap 1846 XT automated blood pressure monitor.
AB  - Accurate blood pressure (BP) measurement is important for the detection and
      treatment of hypertension. Despite widespread use of automated devices, there is
      limited published evidence for their reliability and accuracy. To determine the
      reliability and accuracy of the Dinamap 1846XT (Critikon Corporation, Tampa, FL,
      USA), a commonly used non-invasive oscillometric BP monitor The Dinamap was
      evaluated against the mercury manometer in 70 randomly selected adult
      hospitalised medical patients. Each individual underwent three sets of
      standardised BP measurement by automated method and three sets by mercury
      manometer by two independent observers. Reliability of BP measurement was
      assessed by repeated measures analysis. Dinamap accuracy was evaluated according
      to the American Association of Medical Instrumentation (AAMI) and British
      Hypertension Society (BHS) guidelines. Most patients were either normotensive or
      had stage I hypertension. The Dinamap tended to overestimate lower diastolic BP,
      and displayed poor reliability (P < 0.05). despite meeting aami guidelines, only
      59% of systolic and 56% of diastolic dinamap readings were within 5 mm hg of the
      mercury manometer and 84% of systolic and 80% of diastolic readings were within
      10 mm hg (bhs grade c). systolic and diastolic accuracy were worse with pressures
      >160/90 mm Hg (grade D) although these measures were based on a smaller sample of
      subjects. In conclusion the Dinamap yields inaccurate estimates of both systolic
      and diastolic BP even under standardised, and thus optimal conditions. This
      inaccuracy is exaggerated at higher BP (>160/90 mm Hg), although the number of
      measurements at higher pressures was small. We recommend that this device not be
      used when accurate BP measurement is needed for therapeutic decision-making.

PMID- 12214263
TI  - Efficacy of very low dose perindopril 2 mg/indapamide 0.625 mg combination on
      left ventricular hypertrophy in hypertensive patients: the P.I.C.X.E.L. study
      rationale and design.
AB  - The PICXEL study is designed to evaluate the effects of long-term administration
      of very low-dose combination perindopril 2 mg/indapamide 0.625 mg (Per/Ind) vs
      enalapril in reducing left ventricular hypertrophy (LVH) in hypertensive
      patients. This multicentre, controlled, randomised, double-blind, parallel group
      study is carried-out to assess the variation of left ventricular mass index
      (LVMI) after treatment, using a centralised control of M-mode echocardiography
      determinations, and a dedicated software for semi-automatic measurement.
      Following a 4-week placebo run-in period, hypertensive outpatients aged >/=18
      years, with LVH (LVMI >120 and 100 g/m(2) for men and women, respectively), are
      randomised to receive once daily, over 52 weeks, either Per/Ind or enalapril.
      According to blood pressure levels, the dose may be adjusted. In addition to
      clinical examinations, ECG, blood pressure, heart rate and laboratory assessments
      echocardiographic determinations are performed for selection, at baseline, after
      24 weeks and at the end of the study. The main outcome criteria is the change
      from baseline in LVMI which is considered the primary efficacy criterion; changes
      in blood pressure and echo-Doppler parameters constitute secondary criteria. Two
      sided Student's t-test for independent samples will be used to differentiate the
      effects of the treatment between groups with alpha = 5%, and the inter-group
      difference of LVMI variation will be analysed with a power of 90%. A sample size
      of 500 patients is required making it necessary to randomise at least 550
      patients, based on a 10% proportion of potentially non-assessable patients. The
      results of this study, obtained after applying strict methodological procedures
      and requirements, are expected to provide valuable and reliable information on
      the effects of long-term administration of Per/Ind on LVH, and on its potential
      superiority over enalapril.

PMID- 12214264
TI  - Orthostatic hypotension and Holmes-Adie syndrome. Usefulness of the Valsalva
      ratio in the evaluation of baroreceptor dysfunction.

PMID- 12214265
TI  - Sequential activation and inactivation of G2 checkpoints for selective killing of
      p53-deficient cells by microtubule-active drugs.
AB  - By inducing p53-dependent G2 arrest, the pretreatment with low concentrations of
      DNA damaging drugs (e.g., doxorubicin, DOX) can prevent cell death caused by
      microtubule-active drugs (e.g., paclitaxel, PTX), thus potentially permitting
      selective killing of p53-deficient cancer cells. However, DOX still protects a
      subset of tumor cell lines lacking wt p53 (HL60 and Jurkat leukemia cells), thus
      limiting the utility of protection of cells with wt p53 (e.g., normal cells). The
      present work overcomes this obstacle by adding an abrogator of p53-independent
      checkpoint (e.g., UCN-01) to the DOX-PTX sequence. By inhibiting a p53
      independent pathway, UCN-01 overrode DOX-induced G2 arrest and instead induced G1
      arrest in HL60 and Jurkat, thus propelling these p53-deficient cells from G2 to
      G1. Once they entered mitosis, cells were killed by PTX. Induction of G2 arrest
      with sequential abrogation of a p53-independent checkpoint allows pharmacological
      manipulation of Raf-1/Bcl-2 hyperphosphorylation, PARP and Rb cleavage and cell
      death caused by PTX in p53-deficient cells. Unlike previous approaches, this
      strategy is intended to increase selectivity, not the cytotoxicity of PTX. This
      rational sequence of agents that induces p53-dependent and abrogates p53
      independent arrest represents a cancer-selective strategy for treatment of p53
      deficient tumors.

PMID- 12214266
TI  - Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF
      activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways.
AB  - Dual EGFR/erbB2 inhibition is an attractive therapeutic strategy for epithelial
      tumors, as ligand-induced erbB2/EGFR heterodimerization triggers potent
      proliferative and survival signals. Here we show that a small molecule, GW572016,
      potently inhibits both EGFR and erbB2 tyrosine kinases leading to growth arrest
      and/or apoptosis in EGFR and erbB2-dependent tumor cell lines. GW572016 markedly
      reduced tyrosine phosphorylation of EGFR and erbB2, and inhibited activation of
      Erk1/2 and AKT, downstream effectors of proliferation and cell survival,
      respectively. Complete inhibition of activated AKT in erbB2 overexpressing cells
      correlated with a 23-fold increase in apoptosis compared with vehicle controls.
      EGF, often elevated in cancer patients, did not reverse the inhibitory effects of
      GW572016. These observations were reproduced in vivo, where GW572016 treatment
      inhibited activation of EGFR, erbB2, Erk1/2 and AKT in human tumor xenografts.
      Erk1/2 and AKT represent potential biomarkers to assess the clinical activity of
      GW572016. Inhibition of activated AKT in EGFR or erbB2-dependent tumors by
      GW572016 may lead to tumor regressions when used as a monotherapy, or may enhance
      the anti-tumor activity of chemotherapeutics, since constitutive activation of
      AKT has been linked to chemo-resistance.

PMID- 12214267
TI  - FR901228, an inhibitor of histone deacetylases, increases the cellular
      responsiveness to IL-6 type cytokines by enhancing the expression of receptor
      proteins.
AB  - The related members of the interleukin-6 (IL-6) family of cytokines, leukemia
      inhibitory factor (LIF), oncostatin M (OSM) and IL-6 are inflammatory mediators
      that control differentiated cell functions as well as proliferation. The cellular
      responsiveness to these cytokines is largely determined by the expression of the
      appropriate receptor proteins. The receptor expression profile for each cell type
      is established during differentiation and is often altered during oncogenic
      transformation. Since inhibition of histone deacetylases (HDAC) has the potential
      to re-activate epigenetically silenced genes, we asked whether inhibition of HDAC
      enhances the expression of IL-6 cytokine receptors and, thus, increase desirable
      cytokine responses. We demonstrate that treatment with FR901228 (FR), an HDAC
      inhibitor, increases the responsiveness to LIF in different cell types, including
      normal fibroblasts, epithelial cells, macrophages and splenocytes, as well as
      various tumor cell lines. Depending on the cell type, FR treatment also enhances
      the responsiveness to OSM and IL-6. These effects involve a transcriptional
      induction of the cytokine receptor subunits LIFRalpha, OSMRbeta, gp130, or the
      transcription factor STAT3. FR-specific induction of LIFRalpha occurs
      independently of de novo protein synthesis and cell proliferation and is mediated
      in part by the CBP/p300 coactivator. Chromatin immunoprecipitation experiments
      indicate that the expression of LIFRalpha and gp130 genes correlates with the
      level of acetylated histone 3 associated with the receptor promoter regions. The
      FR-stimulated expression of IL-6-type cytokine receptors in certain tumor cells
      also provided improved conditions for suppression of cell growth by taking
      advantage of the growth inhibitory effect of these cytokines.

PMID- 12214268
TI  - Role for the double-stranded RNA activated protein kinase PKR in E2F-1-induced
      apoptosis.
AB  - The transcription factor E2F-1 induces cell cycle progression at the G1/S
      checkpoint, and deregulation of E2F-1 provokes apoptosis in a wide variety of
      malignant cells. To date only p14(ARF) and p73, a p53 homologue, have been
      identified as E2F-1-inducible genes capable of mediating an apoptotic response.
      Here we show that adenovirus-mediated E2F-1 overexpression in cancer cells
      induces expression and autophosphorylation of the double-stranded RNA-dependent
      protein kinase PKR leading to phosphorylation of its downstream target, the alpha
      subunit of the eukaryotic translation initiation factor 2 (eIF-2alpha) and to
      apoptotic cell death. This PKR-dependent apoptosis occurs in cell lines with
      mutated p53 and in cell lines with mutated p53 and p73, and is significantly
      reduced by the chemical inhibition of PKR activation. Further, PKR(-/-) mouse
      embryo fibroblasts, but not PKR(+/+) mouse embryo fibroblasts, demonstrate
      significant resistance to E2F-1-induced apoptosis. We conclude that an important
      pathway of E2F-1-mediated apoptosis is dependent on PKR activation and does not
      require p53 or p73.

PMID- 12214269
TI  - Gene expression in epithelial ovarian carcinoma.
AB  - We analysed the mRNA levels corresponding to 12,600 transcripts in primary
      cultures of ovarian epithelial cells derived from nine normal ovaries and 21
      epithelial ovarian carcinoma. The class distinction and hierarchical clustering
      of expression data revealed a clear distinction in gene expression between normal
      and carcinoma-derived ovarian epithelial cells. Comparison of expression levels
      revealed 111 genes with mean expression values of >2.5-fold higher in carcinoma
      cells. Similarly, 62 genes were expressed at >2.5-fold higher levels in normal
      ovarian epithelial cells. For a few selected genes, we demonstrate that the
      pattern of differential expression observed in cultured epithelial cells is
      present in the normal ovaries and epithelial ovarian carcinoma. Use of cultured
      epithelial cells represents a novel strategy to study gene expression in a cell
      type specific manner.

PMID- 12214270
TI  - Heterozygosity for p53 promotes microsatellite instability and tumorigenesis on a
      Msh2 deficient background.
AB  - In colorectal tumorigenesis, loss of function of the mismatch repair genes is
      closely associated with genomic instability at the nucleotide level whereas p53
      deficiency has been linked with gross chromosomal instability. We have addressed
      the contribution of these two forms of genetic instability to tumorigenesis using
      mice mutant for Msh2 and p53. As previously reported, deficiency of both genes
      leads to rapid lymphomagenesis Here we show that heterozygosity for p53 also
      markedly reduces survival on an Msh2 null background. We characterized the
      patterns of genomic instability in a small set of tumours and showed that, as
      predicted p53 deficiency predisposes to aneuploidy and Msh2 deficiency leads to
      microsatellite instability (MSI). However, heterozygosity for p53 in the absence
      of Msh2 resulted in increased MSI and not aneuploidy. This implied role for p53
      in modulating MSI was confirmed using a large cohort of primary fibroblast
      clones. The differences observed were highly significant (P<0.01) in both the
      fibroblast clones (which all retained p53 functionality) and the tumours, a
      proportion of which retained p53 functionality. Our results therefore demonstrate
      a dose sensitive role for p53 in the maintenance of genomic integrity at the
      nucleotide level.

PMID- 12214271
TI  - Sck is expressed in endothelial cells and participates in vascular endothelial
      growth factor-induced signaling.
AB  - Sck, a member of the Shc family of cell signaling proteins, has only been studied
      in neuronal cells, though previous studies have demonstrated its expression in
      tissues other than brain. Using RT-PCR and RNase protection assays, we detected
      Sck mRNA expression in endothelial cells, and Sck protein was detected by Western
      blotting using polyclonal and monoclonal antibodies targeting the Sck CH1 domain.
      Immunohistochemistry protocols demonstrate that Sck is expressed in KDR and PECAM
      positive cells found in the mouse retina, mouse heart and human umbilical chord.
      Treatment of human umbilical vein endothelial (HUVE) cells with vascular
      endothelial growth factor (VEGF) leads to the recruitment of Sck to the KDR VEGF
      receptor and an enhanced Sck tyrosine phosphorylation. Sck is recruited to KDR
      tyrosine 1175, as co-immunoprecipitation of KDR and Sck is not observed in VEGF
      treated porcine aortic endothelial cells expressing a receptor mutated at this
      autophosphorylation site. The Sck and Shc SH2 domains, and not the PTB domain,
      mediates its interactions with KDR, as recombinant Sck SH2 domain binds to a
      tyrosine phosphorylated KDR 1175-derived synthetic peptide, but not to a peptide
      synthesized without tyrosine phosphate. Recombinant PLCgamma SH2 domain also
      interacts with the phosphotyrosine 1175 containing peptide. VEGF-induced MAPK
      activation is dependent upon PLCgamma activity, and chimeric proteins consisting
      of the Shc or Sck SH2 domains fused with a cellular internalization sequence
      attenuated this activation. Taken together, these results demonstrate that Sck is
      expressed in vascular endothelial cells, and participates in VEGF-induced signal
      transduction.

PMID- 12214272
TI  - Thioredoxin reductase regulates AP-1 activity as well as thioredoxin nuclear
      localization via active cysteines in response to ionizing radiation.
AB  - A recently identified class of signaling factors uses critical cysteine motif(s)
      that act as redox-sensitive 'sulfhydryl switches' to reversibly modulate specific
      signal transduction cascades regulating downstream proteins with similar redox
      sensitive sites. For example, signaling factors such as redox factor-1 (Ref-1)
      and transcription factors such as the AP-1 complex both contain redox-sensitive
      cysteine motifs that regulate activity in response to oxidative stress. The
      mammalian thioredoxin reductase-1 (TR) is an oxidoreductase selenocysteine
      containing flavoprotein that also appears to regulate multiple downstream
      intracellular redox-sensitive proteins. Since ionizing radiation (IR) induces
      oxidative stress as well as increases AP-1 DNA-binding activity via the
      activation of Ref-1, the potential roles of TR and thioredoxin (TRX) in the
      regulation of AP-1 activity in response to IR were investigated. Permanently
      transfected cell lines that overexpress wild type TR demonstrated constitutive
      increases in AP-1 DNA-binding activity as well as AP-1-dependent reporter gene
      expression, relative to vector control cells. In contrast, permanently
      transfected cell lines expressing a TR gene with the active site cysteine motif
      deleted were unable to induce AP-1 activity or reporter gene expression in
      response to IR. Transient genetic overexpression of either the TR wild type or
      dominant-negative genes demonstrated similar results using a transient assay
      system. One mechanism through which TR regulates AP-1 activity appears to involve
      TRX sub-cellular localization, with no change in the total TRX content of the
      cell. These results identify a novel function of the TR enzyme as a signaling
      factor in the regulation of AP-1 activity via a cysteine motif located in the
      protein.

PMID- 12214273
TI  - Raf-1-induced growth arrest in human mammary epithelial cells is p16-independent
      and is overcome in immortal cells during conversion.
AB  - Using an estrogen-inducible retroviral system, we demonstrate that oncogenic Raf
      1 induces growth arrest and morphological changes in finite lifespan human
      mammary epithelial cells (HMEC). This arrest does not rely on expression of the
      cyclin-dependent kinase inhibitor (CKI) p16(INK4a), nor on changes in expression
      of the CKIs p21(Cip1), p14(ARF), p27(Kip1) or p57(Kip2). The Raf-induced arrest
      is independent of viral oncogene mediated inactivation of p53 and pRB, or c-myc
      overexpression. Flow cytometric analysis demonstrates that cells arrest in both
      G1 and G2. The Raf-induced arrest is mitigated or eliminated in some immortally
      transformed HMEC. Immortal HMEC that have both overcome replicative senescence
      and undergone the recently described conversion process maintain growth in the
      presence of transduced oncogenic Raf-1; they also gain EGF-independent growth and
      a low frequency of anchorage-independent growth. However, HMEC that have overcome
      replicative senescence but have not undergone conversion and HMEC immortalized by
      transduction with the catalytic subunit of telomerase, hTERT, remain severely
      growth arrested. These results indicate that the molecular mechanisms responsible
      for the Raf-1-induced growth arrest may vary among different finite lifespan cell
      types, and that in HMEC, this mechanism is altered during the conversion process,
      rather than as a direct consequence of overcoming senescence or expressing hTERT.

PMID- 12214274
TI  - The ubiquitous and tissue specific promoters of the human SRC gene are repressed
      by inhibitors of histone deacetylases.
AB  - Histone deacetylase inhibitors have generated keen interest as potential
      chemopreventive and chemotherapeutic agents due to their ability to induce cell
      cycle arrest, differentiation, and apoptosis in a diverse group of cancer derived
      cell lines. Activation of the 60 kDa non-receptor tyrosine kinase, c-Src, has
      been a consistent finding in many tumors and tumor derived cell lines, and has
      been implicated in these same cellular processes. We have shown that the histone
      deacetylase inhibitors, sodium butyrate and Trichostatin A, repressed c-Src mRNA
      and protein expression in a dose-dependent manner in cell lines derived from
      cancers of the colon, breast and liver. Our group has previously identified two
      distinct promoters that are responsible for SRC transcription, separated by a
      distance of approximately 1 kb. Sodium butyrate and Trichostatin A strongly
      inhibited activity of each of these highly disparate SRC promoters, demonstrating
      histone deacetylase inhibitors directly repress SRC transcription. This
      repression did not require protein neosynthesis and was not associated with a
      decrease in binding of protein factors essential for either promoter's activity.
      Our finding that sodium butyrate and Trichostatin A inhibit both SRC promoters
      suggest this oncogene may be a major target of these agents, and may explain in
      part their anti-cancer activity.

PMID- 12214275
TI  - Inhibition by Wnt-1 or Wnt-3a of nerve growth factor-induced differentiation of
      PC12 cells is reversed by bisindolylmaleimide-I but not by several other PKC
      inhibitors.
AB  - Wnt-1 and Wnt-3a exhibit redundancy in neural crest development. We have found
      that they do not produce the same effects on PC12 cells, which were obtained from
      the adrenal medulla, a neural crest derivative. However, both Wnt-1 or Wnt-3a
      inhibit nerve growth factor (NGF)-induced neurite outgrowth. The inhibition is
      reversed by the protein kinase C (PKC) inhibitor, bisindolylmaleimide-I, but it
      did not reverse Wnt-1-induced activation of the canonical Wnt pathway. The Wnt-1
      inhibitory effect was not reversed by several other PKC inhibitors, by phorbol
      ester-induced down-regulation of PKC, or by pertussis toxin, which is known to
      inhibit another Wnt signaling pathway, the Wnt/Ca(2+) pathway. We suggest that
      bisindolylmaleimide-I acts by affecting either a pathway downstream from Lef
      1/Tcf in the canonical pathway or a Wnt signaling pathway other than the
      canonical pathway. In either case, the bisindolylmaleimide-I sensitivity of this
      pathway should aid in its identification.

PMID- 12214276
TI  - Rheb is in a high activation state and inhibits B-Raf kinase in mammalian cells.
AB  - Rheb (Ras homolog enriched in brain) is a member of the Ras family of proteins,
      and is in the immediate Ras/Rap/Ral subfamily. We found in three different
      mammalian cell lines that Rheb was highly activated, to levels much higher than
      for Ras or Rap 1, and that Rheb's activation state was unaffected by changes in
      growth conditions. Rheb's high activation was not secondary to unique glycine to
      arginine, or glycine to serine substitutions at positions 14 and 15,
      corresponding to Ras residues 12 and 13, since Rheb R14G and R14G, S15G mutants
      had similarly high activation levels as wild type Rheb. These data are consistent
      with earlier work which showed that purified Rheb has similar GTPase activity as
      Ras, and suggest a relative intracellular deficiency of Rheb GTPase activating
      proteins (GAPs) compared to Rheb activators. Further evidence for relatively low
      intracellular GAP activity was that increased Rheb expression led to a marked
      increase in Rheb activation. Rheb, like Ras and Rap1, bound B-Raf kinase, but in
      contrast to Ras and Rap 1, Rheb inhibited B-Raf kinase activity and prevented B
      Raf-dependent activation of the transcription factor Elk-1. Thus, Rheb appears to
      be a unique member of the Ras/Rap/Ral subfamily, and in mammalian systems may
      serve to regulate B-Raf kinase activity.

PMID- 12214277
TI  - Serial analysis of gene expression in normal p53 null mammary epithelium.
AB  - Much evidence has accumulated implicating the p53 gene as of importance in breast
      carcinogenesis. However, much still remains to be uncovered on the specific
      downstream pathways influenced by this important activator/repressor of
      transcription. This study investigated the effects of a p53 null genotype on the
      transcriptome of 'normal' mouse mammary epithelium using a unique in vivo model
      of preneoplastic transformation. We used SAGE for the comparative analysis of p53
      wild type (wt) and null mammary epithelium unexposed and exposed to hormonal
      stimulation. Analysis of the hormone exposed samples provided a comprehensive
      view of the dramatic changes in gene expression as consequence of the functional
      differentiation of the mammary epithelium in an in vivo system. We detected the
      dysregulation in p53(null) epithelium of <1% of the transcriptome. Changes in
      expression affected not only known p53 target genes, but also several unexpected
      genes such as Expi (Wdnm1), Cyp1b1, Gelsolin, Ramp2 and class I MHC genes. The
      dysregulation of specific genes and their potential use as preneoplastic markers
      was further validated using an independent model of premalignant mammary
      outgrowth lines. This is the first study to examine the transcriptome of very
      early stages of preneoplastic progression in an in vivo model that mimics human
      breast cancer.

PMID- 12214279
TI  - Targeted expression of the receptor tyrosine kinase RON in distal lung epithelial
      cells results in multiple tumor formation: oncogenic potential of RON in vivo.
AB  - RON, a member of the MET proto-oncogene family, has been implicated in the
      progression of certain epithelial cancers. The purpose of this study was to
      determine the oncogenic potential of RON in vivo in lung epithelial cells.
      Transgenic mice were established using surfactant protein C promoter to express
      human RON in the distal lung epithelial cells. These mice were born normal but
      developed multiple lung tumors with distinct morphology and growth patterns.
      Tumors appeared as a single mass in the lung around 2 months of age and gradually
      developed into multiple nodules located mostly in the peripheral portions of the
      lung. A transition from early adenomas to later adenocarcinomas was observed.
      Morphologically, tumors were characterized as cuboidal epithelial cells with a
      type II cell phenotype, grew along the alveolar walls, and projected into the
      alveolar septa. RON was highly expressed and constitutively activated in tumors.
      These results indicate that overexpression of human wild-type RON causes the
      formation of lung tumors with unique biological characteristics in vivo. This
      model provides opportunities to study the role of RON in the pathogenesis of lung
      tumors and to elucidate the mechanisms underlying this distinct lung tumor.

PMID- 12214278
TI  - Ku affects the ATM-dependent S phase checkpoint following ionizing radiation.
AB  - Following exposure to genotoxic stress, proliferating cells actively slow down
      DNA replication through an S phase checkpoint to provide time for repair. The ATM
      dependent pathway plays an important role in the S phase checkpoint response
      following ionizing irradiation. We report that there is a stronger S phase
      checkpoint response in irradiated Ku80(-/-) cells as compared with their wild
      type counterparts, which has no relationship to DNA-dependent protein kinase (DNA
      PK) activity but correlates with a higher ATM activity and with more ATM bound to
      chromatin DNA in such cells. Wortmannin, a nonspecific inhibitor of ATM, not only
      reduces the higher activity of ATM kinase, but also abolishes the stronger S
      phase checkpoint response in Ku80(-/-) cells. Furthermore, a specific ATM
      antisense oligonucleotide abolishes the stronger S checkpoint response in Ku80(-/
      ) cells and renders these cells practically indistinguishable from Ku80(+/+)
      cells for this endpoint. These results in aggregate indicate that the stronger S
      checkpoint in irradiated Ku80(-/-) cells is due to the higher ATM kinase
      activity.

PMID- 12214280
TI  - Isolation of HELAD1, a novel human helicase gene up-regulated in colorectal
      carcinomas.
AB  - To investigate the mechanisms of colorectal carcinogenesis, we searched for genes
      regulated by adenomatous polyposis coli gene product (APC) and identified a novel
      gene, termed HELAD1 (helicase, APC down-regulated 1). A recombinant polypeptide
      representing the ATPases associated with cellular activities (AAA) domain of the
      HELAD1 product showed 3' to 5' helicase activity and exonuclease activity in
      vitro. HELAD1 was abundantly expressed in 16 of 20 colon cancers examined but
      hardly detectable in corresponding non-cancerous mucosae. Treatment of colon
      cancer cells with antisense oligonucleotides suppressed its expression and
      induced apoptosis. These data revealed an importance of HELAD1 in colorectal
      carcinogenesis and suggest that suppression of HELAD1 may be a promising
      therapeutic strategy.

PMID- 12214281
TI  - Characterization of a 500 kb region on 17q25 and the exclusion of candidate genes
      as the familial Tylosis Oesophageal Cancer (TOC) locus.
AB  - The locus for a syndrome of focal palmoplantar keratoderma (Tylosis) associated
      with squamous cell oesophageal cancer (TOC) has been mapped to chromosome 17q25,
      a region frequently deleted in sporadic squamous cell oesophageal tumours.
      Further haplotype analysis described here, based on revised maps of marker order,
      has reduced the TOC minimal region to a genetic interval of 2 cM limited by the
      microsatellite markers D17S785 and D17S751. Partial sequence data and complete
      physical maps estimate the actual size of this region to be only 0.5 Mb. This
      analysis allowed the exclusion of proposed candidate tumour suppressor genes
      including MLL septin-like fusion (MSF), survivin, and deleted in multiple human
      cancer (DMC1). Computer analysis of sequence data from the minimal region
      identified 13 candidate genes and the presence of 50-70 other 'gene fragments' as
      ESTs and/or predicted exons and genes. Ten of the characterized genes were
      assayed for mutations but no disease-specific alterations were identified in the
      coding and promoter sequences. This region of chromosome 17q25 is, therefore,
      relatively gene-rich, containing 13 known and possibly as many as 50 predicted
      genes. Further mutation analysis of these predicted genes, and others possibly
      residing in the region, is required in order to identify the elusive TOC locus.

PMID- 12214284
TI  - The gene for juvenile hyaline fibromatosis maps to chromosome 4q21.
AB  - Juvenile hyaline fibromatosis (JHF) is an autosomal recessive condition
      characterized by multiple subcutaneous nodular tumors, gingival fibromatosis,
      flexion contractures of the joints, and an accumulation of hyaline in the dermis.
      We performed a genomewide linkage search in two families with JHF from the same
      region of the Indian state of Gujarat and identified a region of homozygosity on
      chromosome 4q21. Dense microsatellite analyses within this interval in five
      families with JHF who were from diverse origins demonstrate that all are
      compatible with linkage to chromosome 4q21 (multipoint LOD score 5.5). Meiotic
      recombinants place the gene for JHF within a 7-cM interval bounded by D4S2393 and
      D4S395.

PMID- 12214285
TI  - A rare haplotype of the RET proto-oncogene is a risk-modifying allele in
      hirschsprung disease.
AB  - Hirschsprung disease (HSCR) is a common genetic disorder characterized by
      intestinal obstruction secondary to enteric aganglionosis. HSCR demonstrates a
      complex pattern of inheritance, with the RET proto-oncogene acting as a major
      gene and with several additional susceptibility loci related to the Ret-signaling
      pathway or to other developmental programs of neural crest cells. To test how the
      HSCR phenotype may be affected by the presence of genetic variants, we
      investigated the role of a single-nucleotide polymorphism (SNP), 2508C-->T
      (S836S), in exon 14 of the RET gene, characterized by low frequency among
      patients with HSCR and overrepresentation in individuals affected by sporadic
      medullary thyroid carcinoma. Typing of several different markers across the RET
      gene demonstrated that a whole conserved haplotype displayed anomalous
      distribution and nonrandom segregation in families with HSCR. We provide genetic
      evidence about a protective role of this low-penetrant haplotype in the
      pathogenesis of HSCR and demonstrate a possible functional effect linked to RET
      messenger RNA expression.

PMID- 12214287
TI  - Treatment of acute myeloid leukemia: state-of-the-art and future directions.
AB  - Despite major recent advances in the understanding of the molecular biology of
      the disease, the treatment of acute myeloid leukemia (AML) in adults remains
      challenging. For the 75% of AML patients older than 60 years, currently available
      treatments produce significant toxicity with poor overall response rates and
      survival. In younger patients, standard regimens using cytarabine and an
      anthracycline for induction followed by some form of intensive postremission
      therapy can produce response rates of 70% with 5-year relapse-free survival rates
      of 25% to 40%. Chromosomal analyses define three prognostic categories with
      favorable, intermediate, and unfavorable risk. In older adults, AML appears to be
      an intrinsically resistant disorder of proximal pluripotent hematopoietic stem
      cells. A variety of targeted therapies currently in development include
      modulators of MDR1-mediated drug resistance, immunotherapeutics, angiogenesis
      inhibitors, proapoptotic antisense oligonucleotides, and specific small molecule
      inhibitors of tyrosine kinase and farnesyltransferase. For example, oral
      farnesyltransferase inhibitors have demonstrated activity and tolerability in
      patients with refractory AML and are now in phase II testing. Such targeted
      therapeutics offer the promise of novel antileukemic activity combined with an
      improved therapeutic index.

PMID- 12214288
TI  - Chronic myeloid leukemia: current therapies and the potential role of
      farnesyltransferase inhibitors.
AB  - The treatment of patients with chronic myeloid leukemia (CML) is evolving
      rapidly. With conventional chemotherapy the clinical course is characterized by a
      chronic phase (median duration, 4 to 5 years), followed by an accelerated phase
      with transition to a terminal blast crisis. Treatment with busulfan or
      hydroxyurea does not alter the natural history. Interferon alfa (IFN-alpha)
      prolongs life expectancy by approximately 20 months but is associated with
      significant toxicity. Evidence indicates that bone marrow transplantation from a
      related human leukocyte antigen (HLA)-identical donor can be curative in younger
      patients. However, transplantation is available to only a minority of patients
      and entails severe toxicity and transplant-related mortality. Dramatic advances
      in the understanding of the molecular pathophysiology of CML have led to a new
      era of targeted therapy. The specific tyrosine kinase inhibitor imatinib mesylate
      demonstrates a high level of efficacy in CML with acceptable toxicity.
      Farnesyltransferase inhibitors (FTIs) are another important class of targeted
      agents with the potential to act at multiple sites within dysregulated signal
      transduction networks. ZARNESTRA (formerly R115777, Ortho Biotech Oncology,
      Raritan, NJ), an oral FTI, has shown activity and is well tolerated in both
      chronic- and accelerated-phase patients. With their mechanistic specificity, the
      new modalities offer the promise of increased antileukemic activity and an
      improved therapeutic index.

PMID- 12214289
TI  - Myelodysplastic syndrome overview.
AB  - Myelodysplastic syndrome (MDS) is a heterogeneous hematopoietic stem cell
      disorder characterized by bone marrow dysplasia and peripheral cytopenias. Eighty
      percent of patients found to have MDS are older than 60 years and therefore not
      eligible for the only potentially curative therapy, bone marrow transplantation.
      Currently, there is no standard for treating MDS; therapies range from supportive
      care with transfusions or hematopoietic growth factors and low-intensity
      cytarabine therapy, to intensive anti-acute myeloid leukemia-type chemotherapy.
      Some of these treatments induce a limited hematologic response, but none
      consistently extends survival. Many are highly toxic. More than half of patients
      with MDS die within 3 to 4 years of infections, bleeding complications, or
      progression to acute leukemia. Agents in development for MDS include all-trans
      retinoic acid (ATRA), decitabine, and thalidomide. Farnesyltransferase inhibitors
      modulate many of the cancer-signaling pathways implicated in MDS initiation or
      progression and may therefore be well suited for treatment of these biologically
      diverse hematologic malignancies. Phase I and II clinical studies in our center
      show that the oral FTI ZARNESTRA (formerly R115777, Ortho Biotech Oncology,
      Raritan, NJ) has promising anti-MDS activity, suggesting that further
      investigation of this agent and of this class in MDS is warranted.

PMID- 12214290
TI  - Farnesyltransferase inhibitors: novel compounds in development for the treatment
      of myeloid malignancies.
AB  - The farnesyltransferase inhibitors (FTIs) have been shown in early clinical
      trials to elicit antitumor actions in a broad range of solid and hematologic
      malignancies. The mechanism of FTI action involves blockade of
      farnesyltransferase, an enzyme implicated in multiple cell-signaling pathways
      involved in proliferation, angiogenesis, or decreased apoptosis. Of the four main
      classes of FTIs, two orally bioavailable FTIs have advanced farthest in clinical
      development. ZARNESTRA (formerly R115777, Ortho Biotech Oncology, Raritan, NJ)
      and Sarasar (formerly SCH66336, Schering-Plough, Kenilworth, NJ) have
      demonstrated biologic and clinical activity in a range of solid tumors, and
      Zarnestra phase I trials have documented clinical responses in approximately 30%
      of patients with high-risk leukemias or myelodysplastic syndrome (MDS). The main
      across-class toxicities associated with the use of FTIs are myelosuppression and
      fatigue. Certain toxicities, such as the QTc abnormalities associated with L
      778,123, do not appear to be class related. As results of phase II trials with
      FTIs in acute and chronic myeloid leukemias and in MDS become available,
      clinicians will learn more about the potential role of this class of targeted
      anticancer drugs-and possibly about the clinical distinctions among members of
      this class.

PMID- 12214291
TI  - Farnesyltransferase inhibitors and myeloid malignancies: phase I evidence of
      Zarnestra activity in high-risk leukemias.
AB  - Acute leukemia carries a poor prognosis, especially in older patients,
      emphasizing the need for novel therapies. Reasons for treatment failure include
      high rates of relapse and treatment-related toxicities. Farnesyltransferase
      inhibitors (FTIs), a new class of agents that can interfere with intracellular
      signaling, are good therapeutic candidates for study in these diseases, given the
      relatively high levels of the target enzyme, farnesyltransferase, expressed in
      bone marrow and by peripheral circulating lymphocytes. ZARNESTRA (formerly
      R115777, Ortho Biotech Oncology, Raritan, NJ) is an FTI that has clinical
      activity in solid tumors and antileukemic activity in vitro. In a phase I trial
      of Zarnestra in patients with high-risk leukemia (resistant or relapsed acute
      myeloid leukemia [AML] or acute lymphocytic leukemia [ALL], chronic myeloid
      leukemia [CML] in blast crisis, or AML in poor prognosis subgroups), patients
      experienced an overall response rate of 29%. Zarnestra was well tolerated with no
      dose-limiting toxicities through doses up to 900 mg twice daily. Assays measuring
      inhibition of farnesyltransferase activity showed a reliable inhibition at doses
      greater than 300 mg twice daily, and pharmacokinetic studies indicated that
      Zarnestra accumulated preferentially in the bone marrow in a dose-dependent
      fashion. These results suggest that Zarnestra should be studied further in
      patients with myeloid leukemia.

PMID- 12214292
TI  - Future clinical implications for farnesyltransferase inhibitors in hematologic
      malignancies.
AB  - Progress in molecular biology over the past several years has advanced our
      understanding of the pathology of leukemia. Researchers have identified a long
      list of the cytogenetic and molecular abnormalities associated with these
      diseases. However, a significant unmet need remains for medical therapies for
      leukemia, especially in older patients.

PMID- 12214294
TI  - Presynaptic modulation of sensory neurons in the segmental ganglia of arthropods.
AB  - The afferent terminals of arthropod sensory neurones receive abundant input
      synapses, usually closely intermingled with the sites of synaptic output. The
      majority of the input synapses use the neurotransmitter GABA, but in some
      afferents there is a significant glutamatergic or histaminergic component. GABA
      and histamine shunt afferent action potentials by increasing chloride
      conductance. Though glutamate can also have this effect in the arthropod central
      nervous system, its action on afferent terminals appears to be mediated by
      increases in potassium conductance or by the action of metabotropic receptors.
      The action of the presynaptic synapses on the afferents are many and varied. Even
      on the same afferent, they may have several distinct roles that can involve both
      tonic and phasic patterns of primary afferent depolarisation. Despite the
      ubiquity and importance of their effects however, the populations of neurones
      from which the presynaptic synapses are made, remain largely unidentified.

PMID- 12214295
TI  - Peripheral synapses and giant neurons in whip spiders.
AB  - Among invertebrates the synapses between neurons are generally restricted to
      ganglia, i.e., to the central nervous system (CNS). As an exception, synapses
      occur in the sensory nerves of arachnid legs, indicating that some nervous
      integration is already taking place far out in the periphery. In the antenniform
      legs of whip spiders (Amblypygi), a very special synaptic circuit is present.
      These highly modified legs contain several large interneurons (giant neurons)
      that receive mechanosensory input from 700-1,500 tarsal bristles. Some of the
      sensory cell axons contact a giant neuron at its short, branched dendrite, a few
      at the soma, but most synapse onto the long giant axon. The fine structure of
      these synapses resembles that of typical chemical synapses in other arthropods.
      Although thousands of sensory fibers converge on a single giant neuron, there is
      no reduction in the actual number of sensory fibers, because these afferent
      fibers continue their course to the CNS after having made several en passant
      synapses onto the giant neuron. Touching a single tarsal bristle is sufficient to
      elicit action potentials in a giant neuron. Owing to the large diameter of the
      giant axon (10-20 microm), the action potentials reach the CNS within 55 ms, at
      conduction velocities of up to 7 m/s. However, mechanical stimulation of the
      tarsal bristles does not elicit a fast escape response, in contrast to giant
      fiber systems in earthworms, certain insects, and crayfishes. A quick escape is
      observed in whip spiders, but only after stimulation of the filiform hairs
      (trichobothria) on the regular walking legs. Although the giant fiber system in
      the antenniform legs undoubtedly provides a fast sensory pathway, its biological
      significance is not clearly understood at the moment.

PMID- 12214296
TI  - Peripheral synaptic contacts at mechanoreceptors in arachnids and crustaceans:
      morphological and immunocytochemical characteristics.
AB  - Two types of sensory organs in crustaceans and arachnids, the various
      mechanoreceptors of spiders and the crustacean muscle receptor organs (MRO),
      receive extensive efferent synaptic innervation in the periphery. Although the
      two sensory systems are quite different-the MRO is a muscle stretch receptor
      while most spider mechanoreceptors are cuticular sensilla-this innervation
      exhibits marked similarities. Detailed ultrastructural investigations of the
      synaptic contacts along the mechanosensitive neurons of a spider slit sense organ
      reveal four important features, all having remarkable resemblances to the
      synaptic innervation at the MRO: (1) The mechanosensory neurons are accompanied
      by several fine fibers of central origin, which are presynaptic upon the
      mechanoreceptors. Efferent control of sensory function has only recently been
      confirmed electrophysiologically for the peripheral innervation of spider slit
      sensilla. (2) Different microcircuit configuration types, identified on the basis
      of the structural organization of their synapses. (3) Synaptic contacts, not only
      upon the sensory neurons but also between the efferent fibers themselves. (4) Two
      identified neurotransmitter candidates, GABA and glutamate. Physiological
      evidence for GABAergic and glutamatergic transmission is incomplete at spider
      sensilla. Given that the sensory neurons are quite different in their location
      and origin, these parallels are most likely convergent. Although their
      significance is only partially understood, mostly from work on the MRO, the close
      similarities seem to reflect functional constraints on the organization of
      efferent pathways in the brain and in the periphery.

PMID- 12214297
TI  - Neuromodulation of arthropod mechanosensory neurons.
AB  - Arthropod mechanosensory afferents have long been known to receive efferent
      synaptic connections onto their centrally located axon terminals. These
      connections cause presynaptic inhibition by attenuating the action potentials
      arriving at the axon terminals, thus reducing the synaptic potentials in the
      postsynaptic neurons. This type of inhibition can specifically reduce the
      excitation of selected postsynaptic neurons while leaving others unaffected.
      However, recent research has demonstrated that sensory signals detected by
      arthropod mechanosensory neurons can also be synaptically modulated before they
      ever arrive at the axon terminals. In arachnids and crustaceans, wide and complex
      networks of synapses on all parts of the afferent neurons, including the somata
      and dendrites, provide mechanisms to inhibit or enhance the responses to
      mechanical stimuli as they are being detected. This modulation will affect the
      signal transmission to all axonal branches and postsynaptic cells of the affected
      receptor neuron. In addition to the increased complexity of mechanosensory
      information transmission produced by these synapses, a variety of circulating
      neuroactive substances also modulate these neurons by acting on their
      postsynaptic receptors.

PMID- 12214298
TI  - Efferent controls in crustacean mechanoreceptors.
AB  - Since the 1960s it has been known that central neural networks can elaborate
      motor patterns in the absence of any sensory feedback. However, sensory and
      neuromodulatory inputs allow the animal to adapt the motor command to the actual
      mechanical configuration or changing needs. Many studies in invertebrates,
      particularly in crustacea, have described several mechanisms of sensory-motor
      integration and have shown that part of this integration was supported by the
      efferent control of the mechanosensory neurons themselves. In this article, we
      review the findings that support such an efferent control of mechanosensory
      neurons in crustacea. Various types of crustacean proprioceptors feeding
      information about joint movements and strains to central neural networks are
      considered, together with evidence of efferent controls exerted on their sensory
      neurons. These efferent controls comprise (1) the neurohormonal modulation of the
      coding properties of sensory neurons by bioamines and peptides; (2) the
      presynaptic inhibition of sensory neurons by GABA, glutamate and histamine; and
      (3) the long-term potentiation of sensory-motor synapses by glutamate. Several of
      these mechanisms can coexist on the same sensory neuron, and the functional
      significance of such multiple modulations is discussed.

PMID- 12214299
TI  - Electrophysiological analysis of synaptic interactions within peg sensilla of
      scorpion pectines.
AB  - Pectines are unique, midventral sensory appendages that help direct mating and
      food-finding behaviors in scorpions. Dense two-dimensional arrays of bimodally
      sensitive (chemical and mechanical) peg sensilla form the primary sensory
      structures on pectines. Several qualities of peg sensilla make them well suited
      to electrophysiological investigation, including accessibility, stability of
      extracellular recordings, and the ease with which spiking cells can be identified
      and categorized. Cross-correlations of spontaneous neural activity show signs of
      synaptic interactions between sensillar neurons in all species examined to date
      (Paruroctonus mesaensis, Hadrurus arizonensis, Centruroides vittatus)
      representing three families and two superfamilies. Both excitatory and inhibitory
      interactions have been observed, as well as possible dyadic synaptic arrangement.
      Computer simulations of cross-correlograms are consistent with experimental data
      and may help provide additional insight into functionality of synaptic
      connections. Intra-sensillar interactions, coupled with the topographic order of
      peg sensilla and their central nervous system projections, may allow scorpions to
      precisely resolve microfeatures of chemical stimuli. Future research directions
      include inter-sensillar recordings to determine whether synaptic interactions
      extend between adjacent sensilla. Other unresolved questions that can be
      approached electrophysiologically are whether mechanosensory cells interact with
      chemosensitive cells and how the synaptic circuits function under specific
      chemical and mechanical stimulation.

PMID- 12214300
TI  - Dynamic structural changes of synaptic contacts in the visual system of insects.
AB  - The visual system of insects provides an excellent model to study processes of
      transduction and transmission of photic information, synaptogenesis, synaptic
      plasticity, and wiring between photoreceptors and their visual interneurons in
      the optic lobe. This review describes synaptic contacts between photoreceptors
      and other neurons in the visual system of insects, especially in the fly's first
      optic neuropile (the lamina), and summarizes changes observed in the synapses of
      visual cells that have been reported both in phylogeny and ontogeny, and also
      examples of synaptic plasticity in adult insects that have been evoked by
      intrinsic and extrinsic factors. Plasticity observed in synapses of the insect's
      visual system seems to exemplify not only synaptic contacts in insects but, given
      that similar examples of plasticity have been found in other animal groups, may
      also be a general phenomenon in the nervous system.

PMID- 12214301
TI  - Circadian efferent input to Limulus eyes: anatomy, circuitry, and impact.
AB  - Much is known about the anatomy of Limulus retinal efferent neurons and the
      structural and functional consequences of their activation. Retinal efferent
      axons arise from cell bodies located in the cheliceral ganglia of the brain, and
      they project out all of the optic nerves. Their unique neurosecretory-like
      terminals contact all cell types in lateral eye ommatidia, the retinular cells of
      the median eye, and the internal rhabdom of ventral photoreceptors. Lateral and
      median rudimentary photoreceptors are also innervated. The activity of the
      efferents is circadian. They are active during the subjective night and inactive
      during the subjective day. Activation of the efferents drives dramatic and
      diverse changes in the structure and function of Limulus eyes and causes the
      sensitivity and responsiveness of the eyes to light to increase at night.
      Relatively little is known about the molecular mechanisms that produce these
      structural and functional changes, but one efferent-activated biochemical cascade
      has been identified. The biogenic amine octopamine is released from efferent
      terminals, and an octopamine-stimulated rise in cAMP in photoreceptors, with a
      subsequent activation of cAMP-dependent protein kinase, mediates many of the
      known effects of efferent input. A photoreceptor-specific protein, myosin III, is
      phosphorylated in response to efferent input; this protein may play a role in the
      efferent stimulated changes in photoreceptor structure and function. Anatomical,
      biophysical, biochemical, and molecular approaches are now being effectively
      combined in studies of Limulus eyes; thus, this preparation should be
      particularly useful for further detailed investigations of mechanisms underlying
      the modulation of primary sensory cells by efferent input.

PMID- 12214302
TI  - Efferent innervation of photoreceptors in spiders.
AB  - The anterior median (AM) eye of the nocturnal spider Araneus ventricosus showed a
      marked circadian oscillation of sensitivity, but that of the diurnal spider
      Menemerus confusus showed no circadian oscillation. The AM eyes of the
      noct/diurnal spiders Argiope amoena and A. bruennichii have two types of
      photoreceptor cells with different sensitivities. The more sensitive cells showed
      a circadian oscillation of sensitivity, but the less sensitive cells did not. The
      circadian sensitivity change of the eyes was controlled by efferent
      neurosecretory fibers in the optic nerve. Illuminating the brain increased the
      frequency of efferent impulses in the optic nerve of Argiope, showing that
      certain photosensitive neurons are present in the brain. However, it seemed that
      the cerebral photosensitive neurons may be different from the efferent
      neurosecretory cells. The response of the cerebral photosensitive neurons
      increased transiently following diminution of the light intensity striking the
      eyes. The interaction between the cerebral photosensitive neurons and the eyes
      seemed to play a role in increasing this response.

PMID- 12214303
TI  - Presynaptic inhibition of olfactory receptor neurons in crustaceans.
AB  - Presynaptic inhibition of transmitter release from primary sensory afferents is a
      common strategy for regulating sensory input to the arthropod central nervous
      system. In the olfactory system, presynaptic inhibition of olfactory receptor
      neurons has been long suspected, but until recently could not be demonstrated
      directly because of the difficulty in recording from the afferent nerve
      terminals. A preparation using the isolated but intact brain of the spiny lobster
      in combination with voltage-sensitive dye staining has allowed stimulus-evoked
      responses of olfactory receptor axons to be recorded selectively with optical
      imaging methods. This approach has provided the first direct physiological
      evidence for presynaptic inhibition of olfactory receptor neurons. As in other
      arthropod sensory systems, the cellular mechanism underlying presynaptic afferent
      inhibition appears to be a reduction of action potential amplitude in the axon
      terminal. In the spiny lobster, two inhibitory transmitters, GABA and histamine,
      can independently mediate presynaptic inhibition. GABA- and histaminergic
      interneurons in the lobster olfactory lobe (the target of olfactory receptor
      neurons) constitute dual, functionally distinct inhibitory pathways that are
      likely to play different roles in regulating primary olfactory input to the CNS.
      Presynaptic inhibition in the vertebrate olfactory system is also mediated by
      dual inhibitory pathways, but via a different cellular mechanism. Thus, it is
      possible that presynaptic inhibition of primary olfactory afferents evolved
      independently in vertebrates and invertebrates to fill a common, fundamental role
      in processing olfactory information.

PMID- 12214304
TI  - Genetic determination of biological age in the Mennonites of the Midwestern
      United States.
AB  - Numerous studies have shown that longevity is moderately heritable in human
      populations. Longevity, however, contains limited information on functional
      status, since individuals may exhibit differential survival patterns. In this
      study, we employed a stepwise multiple regression approach to estimate biological
      aging in a Mennonite population, using chronological age as a dependent variable
      and various predictors of chronological age including subphenotypes related to
      diabetes, coronary heart disease, hypertension, renal function, and markers of
      functional ability. The residual (the difference between chronological and
      predicted ages) is considered a marker of biological age. In fact, two different
      data sets were used to obtain residuals due to the availability of data. In each
      analysis, chronological age was regressed on predictor variables in a stepwise
      manner, retaining the variables significant at the 5% level. The first analysis
      (N=729) included 6 significant predictors (R(2)=44.3%): glucose, blood urea
      nitrogen (BUN), cholesterol, albumin, systolic blood pressure (SBP), and ln
      potassium, and the second analysis (N=232) included 9 significant predictors
      (R(2)=71.5%): BUN, albumin, SBP, low-density lipoprotein cholesterol, forced
      expiratory volume in 1 sec (FEV1), grip strength, trunk flexibility, reaction
      time, and FEV1xsex. Using a variance components approach, we found that the data
      set-specific residuals were significantly heritable (h(2)+/-SE): first
      analysis=0.265+/-0.106, and second analysis=0.469+/-0.180. The residuals from the
      second data set appear to be more informative for biological aging, perhaps due
      to the inclusion of functional ability-related phenotypes in addition to the
      blood chemistry variables. In summary, we have shown that markers of biological
      aging in Mennonites are under substantial additive genetic influences.

PMID- 12214305
TI  - Hand grip strength: a phenotype suitable for identifying genetic variants
      affecting mid- and late-life physical functioning.
AB  - Physical functioning late in life has been shown to be affected by genetic
      factors. Only a few genetic variants have been suggested to be associated with
      physical functioning, and this only in selected populations (e.g., young healthy
      males and elite athletes). Declining physical functioning late in life is a major
      problem in terms of prevalence, morbidity, functional limitations, and quality of
      life. It is therefore of interest to find a phenotype reflecting physical
      functioning which has a relatively high heritability and which can be measured in
      large samples. Hand grip strength is known to be associated with muscular
      functioning in other muscle groups and with activities of daily living (ADL)
      functioning, and it predicts incident disability. We studied 1,757 Danish twin
      pairs aged 45-96 years, and found that this phenotype has a heritability of 52%
      (95% confidence interval (CI), 48-55%). A powerful design to detect genes
      associated with a phenotype is obtained using the extreme discordant and
      concordant sib pairs, of whom 28 and 77 dizygotic twin pairs, respectively, were
      found in this study. Hence grip strength is a suitable phenotype for identifying
      genetic variants of importance to mid- and late-life physical functioning.

PMID- 12214306
TI  - Case-control study of genetic and environmental influences on premature death of
      adult adoptees.
AB  - Genetic and environmental influence on risk of premature death in adulthood was
      investigated by estimating the associations in total and cause-specific mortality
      of adult Danish adoptees and their biological and adoptive parents. Among all
      14,427 nonfamilial adoptions formally granted in Denmark during the period 1923
      through 1947, we identified 976 case families in which the adoptee died before a
      fixed date. As control families, we selected 976 families where the adoptees were
      alive on that date, and matched to the case adoptees with regard to gender and
      year and month of birth. The data were viewed as a cohort of case parents and a
      cohort of control parents, and lifetime distributions in the two cohorts were
      compared using a Cox regression, stratified with regard to the matching
      variables: gender and year of birth. In the main analyses, the sample was
      restricted with regard to birth year of the adoptees, and age of transfer to the
      adoptive parents, and age at death was restricted to the same range for parents
      and offspring (25-64 years) in order to consider a symmetric lifetime
      distribution. This reduces the sample to 459 case families and 738 control
      families. Various truncations, restrictions, and stratifications were used in
      order to examine the robustness of the results. The results showed a higher
      mortality among biological parents who had children dying in the age range 25
      through 64 years, and this was significant for death from natural causes,
      infectious causes, vascular causes, and from all causes combined. There were no
      significant effects for the adoptive parents. This study supports that there are
      moderate genetic influences on the risk of dying prematurely in adulthood, and
      only a small, if any, effect of the family environment.

PMID- 12214307
TI  - Evidence for a major gene influencing risk of pancreatic cancer.
AB  - Family history of pancreatic cancer, the fifth leading cause of cancer death in
      the United States, confers a 1.5-13-fold higher risk of developing pancreatic
      cancer. Pancreatic cancer is associated with several genetic syndromes, including
      hereditary breast cancer (BRCA2), familial atypical multiple mole melanoma
      (FAMMM) syndrome, Peutz-Jeghers syndrome, hereditary pancreatitis, and hereditary
      nonpolyposis colorectal cancer (HNPCC). However, these syndromes explain little
      of the observed familial aggregation of pancreatic cancer. We performed complex
      segregation analysis on 287 families ascertained through an index case diagnosed
      with pancreatic cancer at the Johns Hopkins Medical Institutions between January
      1, 1994 and December 31, 1999. We tested for the presence of a major gene
      controlling either the "age-at-onset of pancreatic cancer" of "susceptibility to
      pancreatic cancer," and incorporated smoking data on kindred members as a
      covariate. We found evidence for involvement of a major gene in the etiology of
      pancreatic cancer. Whether inheritance was modeled as "age-at-onset" or
      "susceptibility," nongenetic transmission models were strongly rejected. However,
      modeling "age-at-onset" provided a better fit to the observed data than did
      modeling "susceptibility." The most parsimonious models included autosomal
      dominant inheritance of a rare allele. Under the age-at-onset model,
      approximately 0.7% of the population appears to be at high risk of developing
      pancreatic cancer due to this putative gene, whereas 0.4% of the population is at
      high risk under the susceptibility model. Inclusion of smoking as a covariate did
      not significantly improve the fit of these models. This hospital-based
      segregation analysis of pancreatic cancer found evidence supporting the role of a
      rare major gene influencing risk of pancreatic cancer.

PMID- 12214308
TI  - Analysis of intrafamilial phenotypic variation in neurofibromatosis 1 (NF1).
AB  - The relationship of genetic factors to variable expressivity in neurofibromatosis
      1 (NF1) is poorly understood. We examined familial aggregation of NF1 features
      among different classes of affected relatives. Clinical information was obtained
      from the National NF Foundation International Database on 904 affected
      individuals in 373 families with 2 or more members with NF1. We used multivariate
      probit regression to measure the associations between various classes of
      relatives for each of 10 clinical features of NF1, while simultaneously adjusting
      for covariates including related features, age, and gender. Two distinct patterns
      were observed when we compared associations between first- and second-degree
      relatives, sibs, and parent-child pairs: Lisch nodules and cafe-au-lait spots had
      greater associations between first-degree relatives than between second-degree
      relatives, while subcutaneous neurofibromas, plexiform neurofibromas, cafe-au
      lait spots, and intertriginous freckling had greater associations between sibs
      than between parents and children. In addition, Lisch nodules, subcutaneous
      neurofibromas, and cutaneous neurofibromas had greater associations between
      affected fathers and children than between affected mothers and children. These
      familial patterns suggest that unlinked modifying genes and the normal NF1 allele
      may both be involved in the development of particular clinical features of NF1,
      but that the relative contributions vary for different features.

PMID- 12214309
TI  - On a general class of conditional tests for family-based association studies in
      genetics: the asymptotic distribution, the conditional power, and optimality
      considerations.
AB  - Family-based association tests (FBATs) provide simple and powerful tests to
      detect association between a genetic marker and a disease-susceptibility locus,
      manifest in subjects by a phenotype or disease trait. Here we propose a new class
      of conditional tests for family-based association studies that includes most of
      the established tests and their generalizations. The class of tests is very
      general; it can be applied to longitudinal and multivariate traits or phenotypes,
      multiple genetic markers, and many other situations not yet discussed in the
      literature. For any test in this class, we derive the asymptotic distribution
      under the null hypothesis, the conditional power under any alternative
      hypothesis, and the optimal offset for single degree of freedom tests. The
      proposed methodology is illustrated with a genetic study of asthma.

PMID- 12214310
TI  - Association mapping, using a mixture model for complex traits.
AB  - Association mapping for complex diseases using unrelated individuals can be more
      powerful than family-based analysis in many settings. In addition, this approach
      has major practical advantages, including greater efficiency in sample
      recruitment. Association mapping may lead to false-positive findings, however, if
      population stratification is not properly considered. In this paper, we propose a
      method that makes it possible to infer the number of subpopulations by a mixture
      model, using a set of independent genetic markers and then testing the
      association between a genetic marker and a trait. The proposed method can be
      effectively applied in the analysis of both qualitative and quantitative traits.
      Extensive simulations demonstrate that the method is valid in the presence of a
      population structure.

PMID- 12214311
TI  - Fat distribution, menopausal age, and breast cancer risk: a shared
      preconceptional, maternal/oocyte-mediated link?

PMID- 12214312
TI  - Effective Born radii in the generalized Born approximation: the importance of
      being perfect.
AB  - Generalized Born (GB) models provide, for many applications, an accurate and
      computationally facile estimate of the electrostatic contribution to aqueous
      solvation. The GB models involve two main types of approximations relative to the
      Poisson equation (PE) theory on which they are based. First, the self-energy
      contributions of individual atoms are estimated and expressed as "effective Born
      radii." Next, the atom-pair contributions are estimated by an analytical function
      f(GB) that depends upon the effective Born radii and interatomic distance of the
      atom pairs. Here, the relative impacts of these approximations are investigated
      by calculating "perfect" effective Born radii from PE theory, and enquiring as to
      how well the atom-pairwise energy terms from a GB model using these perfect radii
      in the standard f(GB) function duplicate the equivalent terms from PE theory. In
      tests on several biological macromolecules, the use of these perfect radii
      greatly increases the accuracy of the atom-pair terms; that is, the standard form
      of f(GB) performs quite well. The remaining small error has a systematic and a
      random component. The latter cannot be removed without significantly increasing
      the complexity of the GB model, but an alternative choice of f(GB) can reduce the
      systematic part. A molecular dynamics simulation using a perfect-radii GB model
      compares favorably with simulations using conventional GB, even though the radii
      remain fixed in the former. These results quantify, for the GB field, the
      importance of getting the effective Born radii right; indeed, with perfect radii,
      the GB model gives a very good approximation to the underlying PE theory for a
      variety of biomacromolecular types and conformations.

PMID- 12214313
TI  - Linear scaling approaches to quantum macromolecular similarity: evaluating the
      similarity function.
AB  - The evaluation of the electron density based similarity function scales
      quadratically with respect to the size of the molecules for simplified, atomic
      shell densities. Due to the exponential decay of the function's atom-atom terms
      most interatomic contributions are numerically negligible on large systems. An
      improved algorithm for the evaluation of the Quantum Molecular Similarity
      function is presented. This procedure identifies all non-negligible terms without
      computing unnecessary interatomic squared distances, thus effectively turning to
      linear scaling the similarity evaluation. Presented also is a minimalist dynamic
      electron density model. Approximate, single shell densities together with the
      proposed algorithm facilitate fast electron density based alignments on
      macromolecules.

PMID- 12214314
TI  - Comparison of linear-scaling semiempirical methods and combined quantum
      mechanical/molecular mechanical methods for enzymic reactions. II. An energy
      decomposition analysis.
AB  - QM/MM methods have been developed as a computationally feasible solution to QM
      simulation of chemical processes, such as enzyme-catalyzed reactions, within a
      more approximate MM representation of the condensed-phase environment. However,
      there has been no independent method for checking the quality of this
      representation, especially for highly nonisotropic protein environments such as
      those surrounding enzyme active sites. Hence, the validity of QM/MM methods is
      largely untested. Here we use the possibility of performing all-QM calculations
      at the semiempirical PM3 level with a linear-scaling method (MOZYME) to assess
      the performance of a QM/MM method (PM3/AMBER94 force field). Using two model
      pathways for the hydride-ion transfer reaction of the enzyme dihydrofolate
      reductase studied previously (Titmuss et al., Chem Phys Lett 2000, 320, 169-176),
      we have analyzed the reaction energy contributions (QM, QM/MM, and MM) from the
      QM/MM results and compared them with analogous-region components calculated via
      an energy partitioning scheme implemented into MOZYME. This analysis further
      divided the MOZYME components into Coulomb, resonance and exchange energy terms.
      For the model in which the MM coordinates are kept fixed during the reaction, we
      find that the MOZYME and QM/MM total energy profiles agree very well, but that
      there are significant differences in the energy components. Most significantly
      there is a large change (approximately 16 kcal/mol) in the MOZYME MM component
      due to polarization of the MM region surrounding the active site, and which
      arises mostly from MM atoms close to (<10 A) the active-site QM region, which is
      not modelled explicitly by our QM/MM method. However, for the model where the MM
      coordinates are allowed to vary during the reaction, we find large differences in
      the MOZYME and QM/MM total energy profiles, with a discrepancy of 52 kcal/mol
      between the relative reaction (product-reactant) energies. This is largely due to
      a difference in the MM energies of 58 kcal/mol, of which we can attribute
      approximately 40 kcal/mol to geometry effects in the MM region and the remainder,
      as before, to MM region polarization. Contrary to the fixed-geometry model, there
      is no correlation of the MM energy changes with distance from the QM region, nor
      are they contributed by only a few residues. Overall, the results suggest that
      merely extending the size of the QM region in the QM/MM calculation is not a
      universal solution to the MOZYME- and QM/MM-method differences. They also suggest
      that attaching physical significance to MOZYME Coulomb, resonance and exchange
      components is problematic. Although we conclude that it would be possible to
      reparameterize the QM/MM force field to reproduce MOZYME energies, a better way
      to account for both the effects of the protein environment and known deficiencies
      in semiempirical methods would be to parameterize the force field based on data
      from DFT or ab initio QM linear-scaling calculations. Such a force field could be
      used efficiently in MD simulations to calculate free energies.

PMID- 12214315
TI  - Hydration structure of human lysozyme investigated by molecular dynamics
      simulation and cryogenic X-ray crystal structure analyses: on the correlation
      between crystal water sites, solvent density, and solvent dipole.
AB  - The hydration structure of human lysozyme was studied with cryogenic X-ray
      diffraction experiment and molecular dynamics simulations. The crystal structure
      analysis at a resolution of 1.4 A provided 405 crystal water molecules around the
      enzyme. In the simulations at 300 K, the crystal structure was immersed in
      explicit water molecules. We examined correlations between crystal water sites
      and two physical quantities calculated from the 1-ns simulation trajectories: the
      solvent density reflecting the time-averaged distribution of water molecules, and
      the solvent dipole measuring the orientational ordering of water molecules around
      the enzyme. The local high solvent density sites were consistent with the crystal
      water sites, and better correlation was observed around surface residues with
      smaller conformational fluctuations during the simulations. Solvent dipoles
      around those sites exhibited coherent and persistent ordering, indicating that
      the hydration water molecules at the crystal water sites were highly oriented
      through the interactions with hydrophilic residues. Those water molecules
      restrained the orientational motions of adjoining water molecules and induced a
      solvent dipole field, which was persistent during the simulations around the
      enzyme. The coherent ordering was particularly prominent in and around the active
      site cleft of the enzyme. Because the ordering was significant up to the third to
      fourth solvent layer region from the enzyme surface, the coherently ordered
      solvent dipoles likely contributed to the molecular recognition of the enzyme in
      a long-distance range. The present work may provide a new approach combining
      computational and the experimental studies to understand protein hydration.

PMID- 12214316
TI  - A novel parallel algorithm for large-scale Fock matrix construction with small
      locally distributed memory architectures: RT parallel algorithm.
AB  - We developed a novel parallel algorithm for large-scale Fock matrix calculation
      with small locally distributed memory architectures, and named it the "RT
      parallel algorithm." The RT parallel algorithm actively involves the concept of
      integral screening, which is indispensable for reduction of computing times with
      large-scale biological molecules. The primary characteristic of this algorithm is
      parallel efficiency, which is achieved by well-balanced reduction of both
      communicating and computing volume. Only the density matrix data necessary for
      Fock matrix calculations are communicated, and the data once communicated are
      reutilized for calculations as many times as possible. The RT parallel algorithm
      is a scalable method because required memory volume does not depend on the number
      of basis functions. This algorithm automatically includes a partial summing
      technique that is indispensable for maintaining computing accuracy, and can also
      include some conventional methods to reduce calculation times. In our analysis,
      the RT parallel algorithm had better performance than other methods for massively
      parallel processors. The RT parallel algorithm is most suitable for massively
      parallel and distributed Fock matrix calculations for large-scale biological
      molecules with more than thousands of basis functions.

PMID- 12214317
TI  - Electron localization and delocalization in open-shell molecules.
AB  - Localization and delocalization indices derived in the framework of the quantum
      Atoms in Molecules theory have recently been used to analyze the electron-pair
      structure of closed-shell molecules. Here we report calculations of localization
      and delocalization indices for open-shell molecules at the Hartree-Fock (HF)
      level. Several simple doublet and triplet radical molecules are studied. In
      general, interatomic delocalization between bonded atoms is heavily dependent on
      the order and polarity of the bond. Unpaired electrons also have a significant
      effect on the interatomic delocalization indices. Indeed, for many radicals, the
      analysis of the spin components reveals that the interatomic delocalization is
      very different for alpha and beta spin electrons in many cases. In general, at
      the HF level, the results can be rationalized in terms of orbital contributions.
      However, the definition of localization and delocalization indices is completely
      general, and they could be calculated at any level of theory, provided that the
      one- and two-electron densities are available.

PMID- 12214318
TI  - Genetic training of network using chaos concept: application to QSAR studies of
      vibration modes of tetrahedral halides.
AB  - The chaotic dynamical system is introduced in genetic algorithm to train ANN to
      formulate the CGANN algorithm. Logistic mapping as one of the most important
      chaotic dynamic mappings provides each new generation a high chance to hold GA's
      population diversity. This enhances the ability to overcome overfitting in
      training an ANN. The proposed CGANN has been used for QSAR studies to predict the
      tetrahedral modes (nu(1)(A1) and nu(2)(E)) of halides [MX(4)](epsilon). The
      frequencies predicted by QSAR were compared with those calculated by quantum
      chemistry methods including PM3, AM1, and MNDO/d. The possibility of improving
      the predictive ability of QSAR by including quantum chemistry parameters as
      feature variables has been investigated using tetrahedral tetrahalide examples.

PMID- 12214319
TI  - Direct ab initio dynamics study on the rate constants and kinetic isotope effect
      for the reactions of H atoms with GeDn(CH3)4-n (n = 1-4).
AB  - Direct ab initio dynamic calculations are performed on the reactions of atomic
      hydrogen with GeD(n)(CH(3))(4-n) (n = 1-4) over the temperature range 200-2000 K
      at the PMP4SDTQ/6-311 +G(3df,2p)//MP2/6-31 +G(d) (for n = 2-4) and G2//MP2/6-31
      +G(d) (for n = 1) levels. The corresponding k(H)/k(D) ratios are then calculated
      in order to determine the kinetic isotope effect for the four reactions. For the
      simplest GeD(4) +H reaction, the only one that has available experimental data,
      the calculated canonical variational transition state theory incorporates small
      curvature tunneling correction (CVT/SCT) thermal rate constants, and the
      k(H)/k(D) values are in good agreement with the experimental values within the
      experimental temperature range 293-550 K. For the four GeD(n)(CH(3))(4-4) (n = 1
      4) reactions, the variational effect is small over the whole temperature range,
      whereas the small-curvature effect is important in the lower temperature range.
      Finally, the overall rate constants are fitted to the three-parameter expression
      over the whole temperature range 200-2000 K as 5.8 x 10(8)T(1.68)exp(-929/T), 1.7
      x 10(8)T(1.80)exp(-691/T), 2.58 x 10(8)T(1.71)exp(-706/T), and 1.0 x
      10(7)T(2.08)exp(-544/T) cm(3) mol(-1) s(-1) for the n = 4, 3, 2, and 1 reactions.
      Our work may represent the first theoretical study of the kinetic isotope effect
      for the H-attack on the G-H bonding.

PMID- 12214320
TI  - CHIMERA: a software tool for reaction rate calculations and kinetics and
      thermodynamics analysis.
AB  - This article presents and overviews the CHIMERA program package, which provides a
      user-friendly graphical interface between quantum chemistry and chemical kinetics
      programs. CHIMERA facilitates calculations of rate constants for gas-phase
      reactions using transition state and Rice-Ramsperger-Kassel-Marcus theories. The
      program includes computational modules for simulation of gas-phase kinetics using
      simplified reactor models and for computation of chemical equilibria. The review
      includes a description of the theory implemented in the code, the program
      description, the general strategy of calculations using CHIMERA, and illustrative
      examples of the program application.

PMID- 12214321
TI  - The bioavailability and pharmacokinetics of glucosamine hydrochloride and low
      molecular weight chondroitin sulfate after single and multiple doses to beagle
      dogs.
AB  - OBJECTIVE: The purpose of this study was to determine the oral bioavailability
      and pharmacokinetics of a glucosamine (GL) and the disaccharides of chondroitin
      sulfate (CS) after single and multiple-dosing of a GL/CS combination (Cosamin,
      Cosequin). METHODS: Male beagle dogs (n = 8, 12 kg) received the following
      treatments: (1) IV GL (500 mg)/CS (400 mg), (2) p.o. GL (1500 mg)/CS (1200 mg),
      (3) p.o. GL (2000 mg)/CS (1600 mg), (4) p.o. GL (1500 mg)/CS (1200 mg) QD for
      days 1-7 and p.o. GL (3000 mg)/CS (2400 mg) from days 8 to 14. Blood samples were
      collected over 24 h and glucosamine and the disaccharides of chondroitin sulfate
      were determined. Pharmacokinetic analysis was performed on glucosamine and total
      chondroitin sulfate disaccharides and parameters were compared across treatments
      using ANOVA with post hoc analysis. RESULT: After the IV administration,
      glucosamine declined rapidly in a bi-exponential fashion with a mean (+/- S.D.)
      elimination t(1/2) of 0.52 (0.25) h. GL absorption was relatively fast (C(max) =
      8.95 microg/ml, and T(max) 1.5 h after 1500 mg dose) and the mean bioavailability
      of glucosamine after single dosing was approximately 12%. The extent of
      absorption of chondroitin sulfate as indicated by the mean C(max) (21.5
      microg/ml) and mean AUC (187 microg/ml h) of total disaccharides after dosing
      (1600 mg) provides evidence that chondroitin sulfate is absorbed orally. The
      bioavailability of CS ranged from 4.8 to 5.0% after single dosing and 200-278%
      upon multiple dosing. CONCLUSION: The results of this study show that both
      glucosamine and chondroitin sulfate (measured as total disaccharides) are
      bioavailable after oral dosing. In addition, the low molecular weight chondroitin
      sulfate used in this study displays significant accumulation upon multiple
      dosing.

PMID- 12214322
TI  - Effect of dose and input rate on the brain penetration of BMS-204352 following
      intravenous administration to rats.
AB  - BMS-204352 is a novel maxi-K channel opener that is being developed for the
      treatment for stroke. The current study was designed to evaluate the plasma and
      brain pharmacokinetics of BMS-204352 in rats, in particular, assessing the effect
      of dose and input rate on brain penetration of BMS-204352. Rats (3
      animals/group/time point) received a single intravenous dose of BMS-204352 as 5
      mg/kg bolus, 5 mg/kg 30 min infusion, 5 mg/kg 60 min infusion, and 10 mg/kg bolus
      dose, into the jugular vein. Terminal blood (for plasma) and brain samples were
      collected for up to 9 h post-dose and samples were analyzed for the
      concentrations of intact BMS-204352 using a validated liquid chromatographic
      tandem mass spectrometric method (LC/MS/MS). As dose increased from 5 to 10
      mg/kg, both BMS-204352 C(max) and AUC values increased in plasma and brain,
      somewhat greater in proportion to the increment in dose. Whereas the peak
      concentrations of BMS-204352 were affected by infusion time, overall AUCs were
      comparable across the bolus and infusion groups. Terminal disposition (T-half
      ranged from 1.6 to 2.7 h) of BMS-204352 was unaltered as a function of input
      rate. BMS-204352 crossed the blood-brain barrier with brain-to-plasma (B/P)
      ratios of approximately 7-11. Brain-to-plasma ratios appeared to be independent
      of dose and infusions produced somewhat higher brain penetration (B/P of ca. 11)
      as compared to bolus (B/P of ca. 7-8) dose. The decline of BMS-204352 in the
      brain paralleled that of plasma independent of the input rate and dose.

PMID- 12214323
TI  - Pharmacokinetics and dose proportionality of BMS-204352 after intraarterial
      administration to rats.
AB  - BMS-204352 is a novel maxi-K channel opener that is being developed for the
      treatment for stroke. The current study was designed to evaluate the dose
      proportionality and pharmacokinetics of BMS-204352 in rats. In an open, parallel
      fashion, sixteen rats per gender received a single intraarterial dose of BMS
      204352 as a 3-min infusion into the carotid artery at 0.4, 2.0, 5.0 and 10.0
      mg/kg dose levels. Serial blood samples were collected for up to 24 h post-dose
      and plasma samples were analyzed for the concentrations of intact BMS-204352
      using a validated liquid chromatographic mass spectrometric (LC/MS) method.
      Pharmacokinetic analysis was performed using a non-compartmental method. Results
      revealed a gender difference in the pharmacokinetics of BMS-204352 in rats at all
      doses excluding the first (i.e., 0.4 mg/kg) dose panel. BMS-204352 peak plasma
      concentration (C(max)) and area under the plasma concentration-time curve (AUC)
      values increased in a proportion greater than the increment in dose.
      Specifically, as dose increased in the ratio 1:5:12.5:25, C(max) increased in the
      ratio 1:7:18:31 in male rats and 1:7:22:51 in female rats. The respective AUC
      ratios were 1:6:20:42 in male rats and 1:12:29:77 in female rats. Mean total body
      clearance (CL(T)) values for BMS-204352 ranged from 879-3242 ml/h/kg over the
      four dose levels and generally decreased with increase in dose. Similarly, steady
      state volume of distribution (V(SS)) values ranged from 3621-8933 ml/kg over the
      four dose levels and generally decreased with increase in dose. However, mean
      residence time (MRT) and elimination half-life (T(1/2)) values for BMS-204352
      were independent of dose and ranged from 2.42-4.54 to 2.08-4.70 h, respectively.
      In conclusion, BMS-204352 appears to exhibit dose-dependent pharmacokinetics in
      rats. In addition, there appeared to be some evidence of gender related
      differences in the pharmacokinetics of BMS-204352.

PMID- 12214324
TI  - Comparative pharmacokinetics of single doses of doxylamine succinate following
      intranasal, oral and intravenous administration in rats.
AB  - The intranasal route of administration provides a potential useful way of
      administering a range of systemic drugs. In order to assess the feasibility of
      this approach for the treatment of nausea and vomiting, doxylamine succinate was
      studied in rats for the pharmacokinetics (AUC, C(max), t(max)) following
      intranasal, oral and intravenous administrations. Subjects (six male Sprague
      Dawley rats per time interval for each route of administration) received 2-mg
      doses of doxylamine succinate orally and I-mg doses intranasally and
      intravenously, respectively. The various formulations were formulated in isotonic
      saline (0.9% w/v) at 25 +/- 1 degrees C. Doxylamine succinate concentrations in
      plasma were determined with a high-performance liquid chromatographic assay and a
      liquid-liquid extraction procedure. Intranasal and oral bioavailabilities were
      determined from AUC values relative to those after intravenous dosing. Intranasal
      bioavailability was greater than that of oral doxylamine succinate (70.8 vs
      24.7%). The intranasal and oral routes of administration differed significantly
      from the intravenous route of administration. Peak plasma concentration (C(max))
      was 887.6 ng/ml (S.D. 74.4), 281.4 ng/ml (S.D. 24.6) and 1296.4 ng/ml (S.D.
      388.9) for the intranasal, oral and intravenous routes, respectively. The time to
      achieve C(max) for the intranasal route (t(max)=0.5 h) was faster than for the
      oral route (t(max)=1.5 h), but no statistically significant differences between
      the C(max) values were found using 95% confidence intervals. The results of this
      study show that doxylamine succinate is rapidly and effectively absorbed from the
      nasal mucosa.

PMID- 12214325
TI  - Importance of entero-salivary recirculation in paracetamol pharmacokinetics.
AB  - The contribution of an entero-salivary recirculation (salivary secretion
      swallowed-reabsorption of drug from the gastrointestinal tract) to the values of
      the pharmacokinetic parameters of paracetamol was studied in a two-way crossover
      design. Five healthy volunteers took a tablet of Paracetamol (500 mg) in two
      occasions separated by a washout period. The difference between the two
      treatments consisted of saliva that was allowed or not to be swallowed during the
      4 h of study. No statistically significant differences were found in the values
      of the pharmacokinetic parameters between treatments. The half-life time
      calculated from salivary levels was similar to the values previously reported by
      other authors. The percent of the oral dose excreted in saliva during 4 h of
      study was very low (0.1%). Secondary peaks appeared in 8 of 10 profiles. The lack
      of influence of salivary secretion on the pharmacokinetic parameters of
      Paracetamol and the low percent secreted in this fluid suggests that entero
      salivary recirculation is a possible physiological phenomenon undergoing after
      oral administration, but it is not one of the principal phenomenon that defines
      the pharmacokinetic of the drug. We confirm that working with salivary samples in
      pharmacokinetic studies of paracetamol is a useful tool.

PMID- 12214326
TI  - The outstanding metabolic stability of a 14C-labeled beta-nonapeptide in rats--in
      vitro and in vivo pharmacokinetic studies.
AB  - IN VITRO STUDIES: In CaCo-2 cell monolayers the beta-nonapeptide H(beta-HAla-beta
      HLys-beta-HPhe)(3)-OH.4HCl (1), (14)C-labeled on both C atoms of the CH(2)-CO
      moiety of the central beta-HPhe residue, showed a low intrinsic permeability
      (<1%) and is subject to a prominent efflux system. The beta-peptide (1) binds to
      human and rat plasma protein in vitro independent of the concentration of 1 and
      of the species (30-36% bound fraction at 50, 500, and 5000 ng/ml), and has only
      low affinity for the corresponding blood cells (less than 5% of compound 1 in
      blood cells). IN VIVO STUDIES: The in vivo pharmacokinetic characteristics after
      i.v. administration of 5 mg/kg (to male rats and to bile-duct-operated rats)
      were: (i) negligible in vivo biotransformation of 1 (in urine, plasma and feces
      unchanged 1 represented virtually the only compound-related molecule); (ii) rapid
      initial decline (0-8 h post dose) of levels of compound 1 in blood and plasma
      followed by a slower decline (8-96 h post dose); (iii) in non-operated animals
      after 96 h only 38% of the dose was excreted and after 168 h 49% of the dose was
      found remaining in the carcass; elimination through the intestine wall
      represented the major elimination pathway in non-operated animals while in bile
      duct-cannulated animals biliary excretion was not found to contribute
      substantially to elimination (iv) quantitative whole-body autoradioluminography
      (QWBAL) investigations revealed that the kidney was by far the most important
      target organ of distribution; other tissues with high concentrations of compound
      related radioactivity were cartilage, lymph nodes, and liver, whereas lowest
      levels were found in white fat and in the brain. After p.o. administration (10
      mg/kg) negligible radioactivity was observed in the systemic circulation,
      indicating negligible absorption; essentially the entire oral dose was recovered
      unchanged in feces collected over a period of 96 h.

PMID- 12214327
TI  - Emotion recognition via facial expression and affective prosody in schizophrenia:
      a methodological review.
AB  - Disturbances in affect recognition may be one of the most pervasive and serious
      aspects of the schizophrenic patient's interpersonal problems. Interest in the
      decoding of emotional information in schizophrenia has focused on facial affect
      recognition with 29 experimental papers on that topic published since 1987. A
      smaller literature exists on the topic of recognition of affect in speech and
      there are at least seven studies, which have examined both face and voice
      perception in the same individuals with schizophrenia. This paper includes a
      comprehensive analysis of the schizophrenia facial affect recognition research
      over the past decade and the schizophrenia literature on affective prosody, and
      provides the first review of the schizophrenia literature on multichannel emotion
      recognition research. The weight of evidence would suggest that individuals with
      schizophrenia experience problems in the perception of emotional material;
      however, the specificity, extent, and nature of the deficits are unclear. Emotion
      recognition research in schizophrenia should be informed by the general
      literature on emotion recognition with serious attention paid to methodological
      issues.

PMID- 12214328
TI  - Adolescents and their parents: a critical review of measures to assess their
      satisfaction with one another.
AB  - The importance of assessing the parent-adolescent relationship has been stressed
      in the literature. However, an integration of studies that have been conducted to
      assess satisfaction in the parent-adolescent relationship is warranted, including
      evaluation of measures to assess their satisfaction with one another. Therefore,
      the purpose of this paper is to provide a critical examination of the clinical
      utility and psychometric properties of such measures. Suggestions for future
      research are also provided.

PMID- 12214329
TI  - Cognitive therapy of depression: pretreatment patient predictors of outcome.
AB  - This review examines the role of patient predictors of outcome in cognitive
      therapy of depression. Studies that meet eligibility criteria are reviewed for
      demonstrated linkage between various predictors (i.e., pretreatment severity,
      historical features, demographic predictors, dysfunctional attitudes and other
      cognitive features, and treatment acceptability) and outcome, and several effects
      are found. Notably, high pretreatment severity scores are associated with poorer
      response to cognitive therapy, as are high chronicity, younger age at onset, an
      increased number of previous episodes, and marital status. High pretreatment
      levels of dysfunctional attitudes and certain beliefs about the nature of
      depression were also found to predict differential response to cognitive therapy
      of depression. Limitations of the research and directions for further
      investigations of patient predictors of outcome in cognitive therapy of
      depression are provided.

PMID- 12214330
TI  - Measurement of parental discipline and nurturance.
AB  - This paper reviews the measurement of parental discipline and nurturance over the
      past 20 years. Discipline and nurturance are two of the most heavily referenced
      constructs in the parenting research literature, but there are varying ways to
      operationalize them with respect to both method and content. The review
      considered 76 questionnaires that purported to assess discipline, nurturance, or
      both. The evaluation included examination of a total of 27 interview schedules
      that used either in-person or telephone structured questions or a vignette format
      and focused on discipline and nurturance or discipline only. A total of 33
      observational systems were reviewed, the majority of which addressed both
      discipline and nurturance. All measures were profiled, and several noteworthy
      instruments were discussed. Recommendations were offered regarding how to
      strengthen measurement and scientific understanding of discipline and nurturance,
      including the need for greater attention to cultural variation and measurement
      equivalence issues.

PMID- 12214331
TI  - Ethnicity and clinical psychology: a content analysis of the literature.
AB  - As the demographics of the U.S. population continues to change and become
      increasingly diverse, clinical psychologists will need to demonstrate their
      competence in providing culturally appropriate treatments to a wide variety of
      populations. This article summarizes a comprehensive content analysis of five of
      the leading scholarly journals in clinical psychology over a 17-year period (1980
      1997). Results indicate that only 29.3% of the published articles in the clinical
      psychology literature included ethnic minority participants. Furthermore, only
      5.4% of the articles actually focused specifically on ethnic minority
      populations. Thus, the clinical psychology literature does not contain adequate
      coverage of ethnically diverse populations in the U.S., despite their growing
      numbers. This content analysis provides the field with a baseline for future
      comparison to determine whether the field in general is responding to the needs
      of an increasingly diverse society, and to help gauge whether clinical
      psychologists have the scholarly resources available to assist them with becoming
      more culturally competent. Implications for the paucity of research and
      recommendations to ameliorate the problem are discussed.

PMID- 12214332
TI  - [Accessory gallbladder. Diagnosis by ERCP].
AB  - The double gallbladder and the accessory gallbladder are rare congenital
      anatomical variations, but important due to an increased risk of gallstones and
      biliary tree malformations. Most cases have been diagnosed incidentally during
      surgery. A trabecular-type accessory gallbladder diagnosed by ERCP is hereby
      described.

PMID- 12214333
TI  - [Intussusception in adults. Case report with uncommon etiology and review of the
      literature].
AB  - OBJECTIVE: To present a case of adult intussusception with uncommon etiology.
      BACKGROUND: Intussusception is a relatively common cause of intestinal
      obstruction in children, but is a rare clinical entity in adults, representing
      less than one per cent of intestinal obstruction in this patient population.
      METHOD: We report on 72-year old female patient with intestinal obstruction due
      to ileocolic intussusception related to leiomyosarcoma of the terminal ileum. A
      synchronic adenocarcinoma in the cecum was identified. The patient underwent
      right hemicolectomy and terminal ileum resection with primary anastomosis. Her
      postoperative course was uneventful. The patient is free of all evidence of
      disease at 2 year of follow-up. A thorough review of the literature of adult
      intussusception was carried out. CONCLUSION: From this review, the recommendation
      is to resect all cases of adult intussusception, different from the recommended
      approach in pediatric population.

PMID- 12214334
TI  - [Surgical treatment of acute pancreatitis. A review].
AB  - A review of the literature about the last trends in the surgical treatment of
      acute pancreatitis is carried out. The review was on Mexican literature and in
      the Internet.

PMID- 12214335
TI  - [Non-alcoholic steatohepatitis].
AB  - Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that occurs in
      patients with no significant alcohol consumption; it is not histologically
      different from alcoholic hepatitis because it presents macrovesicular steatosis,
      hepatocellular necrosis, mixed inflammatory infiltrate, and various stages of
      fibrosis in addition Mallory bodies in some patients. Some authors have even
      described NASH as a benign disease; however, it is presently considered a
      potentially serious disease that may evolve into liver cirrhosis and probably,
      liver cancer. It is more often related to female sex, obesity, and dyslipidemia,
      although it may be present in other population groups and associated with other
      factors. Its origin may be multifactorial, including insulin resistance, protein
      glycation, oxidative stress, and others. The disease may be asymptomatic and
      found in routine physical exams when the patient shows increased
      aminotransferases with no other explanation. At present the only specific
      diagnosis procedure is liver biopsy. The sole available current treatment is body
      weight control, normalizing glucose and lipid blood levels, as well as the
      administration of some medication, as illustrated in the subsequent article.

PMID- 12214336
TI  - [Usefulness of botulinum toxin in gastrointestinal disorders].
AB  - Botulinum toxin (Botox) produced by Clostridium botulinum is a potent
      neuromuscular blocker agent that inhibits acetylcholine release from presynaptic
      nerve endings. This effect was confirmed in the smooth muscle of the
      gastrointestinal tract and led to clinical trials investigating the efficacy of
      Botox for treatment of several gastrointestinal disorders. Multiple controlled
      studies have shown that Botox is effective in short-term management of achalasia.
      Botox reduces lower esophageal sphincter pressure, improves esophageal clearance,
      and alleviates symptoms in up to 70% of patients; however, its long-term efficacy
      decreases to 30% and repeated injections are often necessary. Botox is reserved
      for older patients and with high surgical risk. The main predictors of a good
      response are older age and presence of vigorous achalasia. Biliary or pancreatic
      sphincter of Oddi dysfunction (SOD) has been another indication for Botox
      administration. Transendoscopic injection of Botox in the papilla of Vater has
      shown relief of symptoms in more than 50% of cases of SOD. Furthermore, a Botox
      clinical response in this condition can predict a long-term benefit with
      endoscopic sphincterotomy. Botox decreases resting anal pressure, has healing
      rates of approximately 80% at six months after injection in patients with chronic
      anal fissure, and has a better outcome than topic nitroglycerine. Case reports
      have shown good results with Botox administration in treatment of diffuse
      esophageal spasm, anismus, oropharyngeal dysphagia, anterior rectocele, and
      secondary achalasia. Administration of botulinum toxin has a low rate of adverse
      reactions and complications.

PMID- 12214337
TI  - [Treatment of non-alcoholic steatohepatitis (NASH). A comparative study of
      ursodeoxycholic acid and alpha-tocopherol. A preliminary report].
AB  - BACKGROUND: At the present time, there is no accepted treatment for non-alcoholic
      steatohepatitis (NASH); nevertheles, there are some reports of non-controlled
      studies with apparently good answer with ursodeoxycholic acid (UDCA) as much with
      alpha-tocopherol (aTP). OBJECTIVE: To value the clinical, biochemical and hepatic
      ultrasound (US) response in patients with NASH in treatment for 1 year with UDCA
      or aTP, as well as to establish tolerance, undesirable effects and fulfillment.
      METHOD: Three patients received UDCA (250 mg TID) and six aTP (100 mg TID).
      Changes in hepatic function test and US were analyzed. All patients were women
      with an average age of 52 years, body mass index of 27, five with diabetes
      mellitus (DM) type II. RESULTS: Fulfillment of treatment was 95%; undesirable
      effects were not reported; clinical course was asymptomatic and clinically we did
      not observe important changes; US showed favorable changes in four patients
      (44%), two in each group. Alkaline phosphatase was normalized in patient who
      initially registered it as high. ALT and AST average diminished by 40% and
      normalization was obtained in five of six patients in treatment with aTP (83%)
      and in one of the UDCA group (33%). No statistically significant difference was
      obtained. CONCLUSIONS: The group is small and requires more persons and to be
      compared with a control group. It is possible that both drugs can be useful in
      the treatment of NASH; they are well tolerated and allow good fulfillment.

PMID- 12214338
TI  - [Results of 21 years of surgery in iatrogenic lesions of the bile ducts].
AB  - OBJECTIVE: To report our results with surgical procedures for treatment of
      iatrogenic injuries of bile duct. SETTING: Tertiary-level health care hospital.
      DESIGN: Retrospective, observational, and descriptive study. MATERIAL AND METHOD:
      We studied all patients operated on due to iatrogenic of injuries of the bile
      duct over the last 21 years (1980-2001). We analyzed the following variables:
      age; gender; previous bile duct surgical procedure; auxiliary diagnosis; type of
      bile duct injury according to Bismuth's classification; surgical procedure used;
      non-related mortality, and postoperative morbimortality. RESULTS: Fifty four
      patients were operated on (46 female, eight male) ranging from 19 to 71 years of
      age; 39 were sent to the hospital, 15 were injured at the hospital in 7,098
      gallbladder and bile duct procedures (0.21%), 83.3% in open cholecystectomy, and
      16.6% in laparoscopic cholecystectomy. In 86% of cases, diagnosis was made by
      percutaneous cholangiography and injuries types were: I = 13%, II = 26%, III =
      50%, IV = 9.2%, and V = 1.8%. Roux-en-Y intrahepaticojejunostomy was the most
      common procedure (51.9%) followed by hepaticojejunostomy (37%). Of 54 surgical
      patients, five died due to situations unrelated to bile duct illness, and they
      were cared for more than one year without complications; 46 patients (85.2%) did
      not show strictures, three patients (5.5%) were reoperated on because of
      strictures, all without recurrent strictures for more than one year of care, with
      a total of good results of 90.7%; mortality: four patients (7.2%), and
      complications after procedure: 11%. Strictures were developed during the first
      year after surgical procedure. CONCLUSION: Our results are similar to others
      found in researches from Mexico and other countries; therefore, we recommend long
      term care of patients.

PMID- 12214339
TI  - [Biliary stents for reconstruction in bile duct injuries. The role of bile
      acids].
AB  - Biliary stents, placed either surgically, endoscopically or radiologically are a
      frequent palliative and/or curative option for treatment of obstructive jaundice.
      Stones or sludge formation above or inside the stent are of major concern in that
      they cause dysfunction of the stent that needs prompt replacement. To evaluate
      the efficacy of ursodeoxycholic acid (UDCA) for long-term management of
      surgically placed biliary stents after iatrogenic injury, a prospective,
      controlled, randomized trial was conducted. METHOD: Patients with biliary tract
      reconstruction caused by iatrogenic injury that required a transanastomotic stent
      were randomized into a control group (N: 29) and into a UDCA (15 mg/kg day)
      treated group (N: 30). Patients were followed on an external basis and a
      cholangiogram was obtained to verify stent patency. Liver function tests were
      also analyzed. RESULTS: The two groups were compared and no differences were
      observed. UDCA treated patients had significant elevation of transaminases and
      alkaline phosphatase. Two patients in the control group and four in the treated
      group developed lithiasis and/or sludge. CONCLUSION: No advantages were shown
      with administration of UDCA to maintain the biliary stents patent and to prevent
      neoformation of lithiasis and/or sludge. We conclude that no benefit is obtained
      with administration of UDCA to patients with biliary reconstruction and a
      transanastomotic stent.

PMID- 12214340
TI  - [Endoscopic cholangiography in mild acute biliary pancreatitis: when and for
      whom?].
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP), with or
      without sphincterotomy, has been widely used in patients with severe biliary
      acute pancreatitis (BAP) or those with cholangitis and/or obstruction of the
      biliary tree. Its use in subjects with mild BAP is more controversial. AIM: To
      optimize use of ERCP in patients with mild pancreatitis due to gallstones by
      identifying clinical and biochemical predictors of choledocholithiasis. MATERIAL
      AND METHOD: The clinical and biochemical data, images, and outcomes of 83
      patients with mild BAP hospitalized at the Instituto Nacional de Ciencias Medicas
      y Nutricion "Salvador Zubiran" from January 1, 1988 to May 30, 2000 were
      retrospectively analyzed. All patients received elective cholecystectomy at
      hospital admission. In 35 cases, ERCP was performed before cholecystectomy (group
      A). The remaining 48 were operated on without ERCP (group B). In 30, transcystic
      cholangiography was done. Forty-seven (57%) were female. Mean age was 47 years
      (19-90). Mean time between onset of AP and hospital admission was 2.2 days (1
      15), and between clinical onset and cholecystectomy, eight days (1-26).
      Statistical differences were evaluated by non-parametric methods. An univariated
      and multivariated analysis was performed looking for data to identify
      choledocholithiasis. RESULTS: Choledocholithiasis was found in 27 cases (32%), 18
      from group A (51%), and nine for group B (19%) (RR = 4.58, IC 95% = 1.7-12.25, p
      = 0.004). ERCP was performed in all cases because of clinical suspicion of
      choledocholithiasis (jaundice, bilirubin, and alkaline phosphatase alteration
      and/or choledochal dilation); however, none of the patients of group B in whom
      choledocholithiasis was operatively diagnosed showed biochemical or radiologic
      alterations. Subjects with choledocolithiasis presented more frequently a history
      of biliary pain (RR = 5.75, IC 95% = 1.76-18.7), jaundice (RR = 3.07, IC 95% =
      1.15-8.16) and/or alkaline phosphatase elevation (RR = 4.11, IC 95% = 1.3-12.7).
      CONCLUSION: The high frequency of choledocholithiasis in subjects with mild
      biliary pancreatitis warranted radiologic exploration of the biliary tree in all
      patients submitted to cholecystectomy. In those with jaundice, alkaline
      phosphatase elevation and/or a history of biliary pain, ERCP should be performed
      prior to the operation; in others, choledocholithiasis can be discharged by
      operative transcystic cholangiography. Therapeutic measures for treating
      choledocholithiasis should be adapted to hospital facilities.

PMID- 12214341
TI  - [Solid-cystic pseudopapillary tumor of the pancreas: acute post-traumatic
      presentation. Case report and review of the literature].
AB  - OBJECTIVE: To report an infrequent case of pancreatic pseudopapillary solid-cyst
      tumor, known as Frantz tumor, discovered after blunt abdominal trauma, and to
      carry out a review of the literature. BACKGROUND: Frantz's tumor is a very
      uncommon low-grade malignant papillary-cystic neoplasm of the pancreas that is
      relatively frequent in young black women and was first described by Frantz in
      1959. CASE REPORT: We present the case of a 15-years-old female patient who, 24 h
      after blunt abdominal trauma, came to the emergency room with intense abdominal
      and atypical pain and a palpable mass in the left upper quadrant. It was
      initially diagnosed as a post-traumatic pancreatic pseudocyst. The patient
      underwent distal pancreatectomy with spleen preservation; the histopathologic
      report was a pseudopapillary solid and cystic tumor of the pancreas without
      malignant cells. Clinical evolution has been satisfactory without recurrence of
      the tumor at 14 months of follow-up. CONCLUSIONS: Frantz's tumor has benign
      biologic behavior and treatment of choice consists of surgical resection. Outcome
      after surgical resection is excellent with 90% survival in the long term. Tumoral
      recurrence has been described in approximately 10% of patients.

PMID- 12214342
TI  - [Inflammatory pseudotumor of the retroperitoneum].
AB  - Inflammatory pseudotumor is a rare, benign lesion of various organs and tissues,
      characterized by proliferating fibrovascular tissue admixed with inflammatory
      cells of etiology and pathogenesis that are largely unknown. We report a case of
      a 55-years-old woman with acute pancreatitis with a retroperitoneal mass in
      Morrison's space detected by tomography. Aspects concerning incidence, etiology,
      clinical, and histopathologic characteristics are discussed.

PMID- 12214343
TI  - Use of seat belts in cars with different seat belt reminder systems. A study of
      injured car drivers.
AB  - The use of seat belts in cars with different seat belt reminder systems was
      analyzed in a population of 477 injured car drivers, transported by ambulance to
      Umea University Hospital after car crashes. The ambulance personnel acted as
      independent observers regarding the use of seat belts. In this population the non
      users were significantly (multivariate logistic regression) fewer (12%) in cars
      with a combined light and sound reminder, compared to cars without reminder
      (23%). In cars with only a light signal the proportion of non-users was the same
      as in cars without any reminder at all. An introduction of more effective
      reminders, at least in new cars, might be an effective way to increase seat belt
      usage rates in the long-term.

PMID- 12214344
TI  - The association between body habitus, restraint use, and fatality in motor
      vehicle collisions.
AB  - The purpose of this study was to determine if there is an association between
      body habitus, restraint use, and risk of death in motor vehicle collisions (MVC).
      METHODS: The 1995-1999 National Automotive Sampling System Crashworthiness Data
      System was utilized. RESULTS: Body habitus, when described by height and weight,
      is associated with fatality rates in restrained drivers. Body mass index as a
      descriptor of body habitus was not associated with fatality rates. CONCLUSIONS:
      The 50th percentile male Hybrid III Crash Dummy plays a major role in vehicular
      cabin interior design and crash testing. For drivers with a dissimilar body
      habitus, the vehicle cabin/body fit changes and the safety features perform
      differently which may account for these observations.

PMID- 12214345
TI  - Comparison of seat belt force-limiting methods using the MADYMO multi-body/finite
      element program.
AB  - Belt force can be limited by a device in the belt retractor hardware or with
      force-limiting as an integral part of the webbing force/strain properties. In
      this research, MADYMO multi-body/finite element models of a 50th percentile
      Hybrid-3 male passenger in an airbag-equipped 4-door mid-size sedan were set up
      to compare occupant injury response under loading 1) from a baseline standard
      (non-force-limiting) belt system, 2) from a retractor-based force-limiting
      system, and 3) from a webbing-based force-limiting system. Chest acceleration was
      similar for the two force-limiting designs but the peak was approximately 10%
      greater for the standard belt. The magnitude of the head acceleration was similar
      for all three belts while the duration of these accelerations was much narrower
      for the force-limiting belts. Chest compression was similar for both force
      limiting methods, and was about 60% less than the standard belt case. Compared to
      the baseline system and the retractor-based system, webbing-based force-limiting
      allowed greater pelvic excursion and a corresponding increase in femur force. It
      is concluded that webbing-based force limiting has some potential for reducing
      head and chest responses but these reductions must be evaluated with respect to
      other considerations such as submarining potential, non-frontal impact response,
      and future concepts like programmable force limiting.

PMID- 12214346
TI  - The role of cocaine in fatal crashes: first results of the Quebec drug study.
AB  - As part of a major undertaking to establish the contribution of drugs in road
      crashes in Quebec, the present study focuses on the role of cocaine. Coroner,
      forensic laboratory and police accident records from April 1999 to December 2000
      were matched for 265 fatally injured drivers of passenger vehicles. Cocaine was
      found in 7.9% of urine samples and 6.0% of blood samples. In order to set up a
      control group, two roadside surveys were conducted in August 1999 and 2000. The
      survey sample was distributed proportionately to the number of fatal accidents
      per time of day and day of the week. During both daytime and nighttime, a total
      of 11,952 drivers participated in the two surveys among which 11,574 provided a
      breath sample (96.8%), 8,177 a saliva sample (68.4%) and 5,931 a urine sample
      (49.6%). Cocaine was detected in 1.1% of urine samples and 1.0% of saliva samples
      of the driving population. In both fatally injured drivers and driving
      population, cocaine was found mostly (> 90%) in four main types of combination:
      cocaine alone, cocaine + cannabis, cocaine + alcohol, cocaine + cannabis +
      alcohol. The data collected allowed two different analyses: a case-control
      (urine/urine) and a responsibility analysis (case-case approach) that compares
      cocaine cases to drug-free cases. Despite some data limitations, all analyses for
      the four main types of combination clearly suggest that cocaine use plays a role
      in fatal crashes.

PMID- 12214347
TI  - The relationship of AIS to peak virtual power.
AB  - All injuries require an expenditure of energy. Here it is postulated that injury
      severity is proportional to Peak Virtual Power (PVP). PVP is compared to AIS
      scores for frontal impact with belted drivers, for all types of injuries and all
      body regions, from the Co-operative Crash Injury Study (CCIS) and NASS-CDS
      databases. The excellent correlations obtained show that the AIS score is
      linearly proportional to Peak Virtual Power, which is proportional to delta V3
      for restrained occupants, and delta V2 for unrestrained occupants. Therefore,
      although phenomenological, AIS appears to measure a physical quantity. It is
      concluded that there appears to be a "Master Curve" of AIS versus mean delta V
      for car occupants, implying that the amount of power for a given injury level is
      a constant, irrespective of injury type. There appear to be significant
      differences between the AIS scores for abdominal injuries between CCIS and NASS
      CDS, and detailed case studies should be conducted to resolve the differences.

PMID- 12214349
TI  - Dynamic performances of different seat designs for low to medium velocity rear
      impact.
AB  - There is good evidence that seat design and impact severities in terms of delta-V
      and acceleration plays a role in AIS 1 neck injury outcomes in the event of a
      rear impact. This study evaluates a number of current production seats to assess
      the AIS 1 neck injury protection potential at different impact severities. Five
      different seat designs were exposed to four different impact severities in a sled
      simulating a rear impact. The same delta-V produced with different peak
      accelerations generated very different dummy responses. Head restraint position
      influenced the angular and horizontal displacement of the head relative to torso
      and the time of head to head restraint contact. The lowest motion of the head
      relative to the torso was found in the two anti-whiplash seats tested. The
      results of the study can be used for the design of future vehicle seats and anti
      whiplash systems.

PMID- 12214348
TI  - HARM 2000: crash cost and consequence data for the new millennium.
AB  - This paper presents the most detailed and current costs per US motor vehicle
      crash victim. These unit costs, which include the first keyed to AIS90, are
      reported by category, body part, whether a fracture/dislocation was involved, and
      MAIS. This level of detail allows for reliable analyses of interventions
      targeting narrow ranges of injuries and, hopefully, for the development of a
      biomechanical injury cost model.

PMID- 12214350
TI  - Do "whiplash" victims with neck pain differ from those with neck pain and other
      symptoms?
AB  - Studying 432 patients with "whiplash" neck pain after a low speed rear-end crash,
      we determined whether those who reported associated symptoms (arm or low back
      pain) differed from those with neck pain only. Exposure variables were: age,
      gender, height, weight, surprised by impact, rotated position of the head, and
      pre-existing cervical or lumbar spinal degeneration. Immediate symptoms were
      considered. Odds ratios (OR) were derived from logistic regression. Only pre
      existing lumbar spinal degeneration was associated with having arm symptoms (OR =
      9.6, CI = 1.1, 83.6) or low back pain (OR = 23.3, CI = 2.6, 206.7) along with
      neck pain.

PMID- 12214351
TI  - Comparison of autopsy, X-ray, and M.R.I. findings following a low speed impact to
      the shoulder.
AB  - The objectives of the study was to generate data useful to engineers improving
      crash test dummies and to physicians in anticipating low speed lateral impact
      injuries to the shoulder. Constant impact mass, distance and variable speeds were
      used to generate impact forces. Twelve unembalmed human cadavers were studied
      within 48 hours of death. Pre-test and Post-test physical, X-Ray, and Magnetic
      Resonance examinations were completed. X-Ray best identified bone injury,
      Magnetic Resonance intratendinous and intramuscular pathology and autopsy joint
      instability. Low speed (3.5-7.0 m/sec) impacts under these testing conditions
      frequently produce soft tissue and bone injuries. Sternoclavicular and
      acromioclavicular joint instabilities were found in 83% of the cadavers. The most
      frequent bone fractures were in the distal clavicle of 42% and labral or rotator
      cuff tears in 13% of the cadavers.

PMID- 12214352
TI  - The association between risk-taking behavior and the use of safety devices in
      adolescents.
AB  - The purpose of this research study was to measure the association between risk
      taking behavior in adolescents and their use of safety devices. The study focused
      on three safety devices: seat belts, motorcycle helmets, and bicycle helmets.
      This is a secondary data analysis using data from the Youth Risk Behavior Survey
      conducted by the Centers for Disease Control and Prevention. The results of this
      study indicate that risky behavior in adolescents is associated with their non
      use of safety devices. In general, risky behavior was more associated with the
      non-use of seatbelts than the use of other safety devices. The results of this
      study suggest that a comprehensive approach to reducing risky behaviors in
      adolescent should be considered when planning injury prevention programs.

PMID- 12214353
TI  - Outcomes of pediatric pedestrian injuries by locations of event.
AB  - Data from the National Pediatric Trauma Registry October 1995-October 2000,
      containing medical records of children under 20 years old hospitalized for
      pedestrian injuries, were examined. Demographics and outcome measures (nature and
      severity of injury, utilization of resources, deaths, and disability at
      discharge) were compared by location of occurrence. Pediatric pedestrian injuries
      resulted in severe outcomes whether the events occurred in driveways, public
      places, or in the road. Off the road injuries accounted for a significant
      proportion (13.2%) of all serious pedestrian injuries and disproportionately
      affected the youngest children. Prevention should consider the child's age and
      the location of injury occurrence.

PMID- 12214354
TI  - Factors influencing the access of severely injured children and elderly patients
      involved in motor vehicle collisions to trauma center care.
AB  - This study was undertaken to determine factors that influence the access to
      trauma center care of pediatric and geriatric patients injured in motor vehicle
      collisions (MVC). Hospital discharge records for 1997 were obtained from the
      Pennsylvania Health Care Cost Containment Council and were analyzed. Of cases
      with an Injury Severity Score of > 15, 52.6% of elderly cases and 48.6% of
      pediatric cases were transported to and received their care in non-trauma center
      hospitals. These very high "mis-triage" rates could not be explained by
      differences in injury severity, body region or population density. In order to
      assess potential out-of-hospital factors, a file containing matched records from
      Emergency Medical Services (EMS) calls and hospital discharges from MVC cases
      across Pennsylvania for the year 1996 was constructed and analyzed. There were no
      significant vital signs differences between trauma center and non-trauma center
      cases, with the single exception of the Glasgow Coma Scale score, for both the
      pediatric and geriatric age groups. A reevaluation of out-of-hospital trauma
      triage is needed.

PMID- 12214355
TI  - Trauma triage criteria system compliance for victims of motor vehicle crashes.
AB  - The objective of this study was to determine the proportion of EMS (Emergency
      Medical Services) Motor Vehicle Collision cases within a large state meeting
      Trauma Triage Criteria (TTC) who are ultimately cared for in trauma centers (TC).
      This cross-sectional observational study utilized EMS records linked with
      hospital discharge records for the year 1997. Using ICDMAP-90 AIS and ISS scores
      were computed. ICD-9-CM and E-codes were used to define acute trauma cases
      resulting from motor vehicle collisions. This population-based system evaluation
      demonstrated effective TTC implementation in urban areas. However, in rural
      areas, many severely injured patients were transported to non-trauma centers.

PMID- 12214356
TI  - The role of driver distraction in crashes: an analysis of 1995-1999
      Crashworthiness Data System Data.
AB  - Five years (1995-1999) of national Crashworthiness Data System (CDS) data are
      analyzed to determine the role of driver distraction in traffic crashes and the
      specific sources of this distraction. Results show that 8.3 percent of the
      drivers were distracted at the time of their crash; after adjustment for the
      large percentage of drivers with unknown distraction status, the percentage rose
      to 12.9 percent. The most frequently cited sources of driver distraction were
      persons, objects or events outside the vehicle (29.4% of distracted drivers),
      adjusting the radio, tape or CD player (11.4%), and other occupants in the
      vehicle (10.9%). Other specific distractions (moving objects in vehicle, other
      objects brought into vehicle, adjusting vehicle or climate controls, eating and
      drinking, cell phones, and smoking) were each cited in only one to four percent
      of the cases. The likelihood of being distracted and the source of distraction
      varied by driver age but not by gender. Results are discussed in light of the
      limitations inherent in the CDS and other crash data, and the need for expanded
      data collection initiatives.

PMID- 12214357
TI  - Evaluation of a program to motivate impaired driving offenders to install
      ignition interlocks.
AB  - Approximately 30,000 alcohol ignition interlocks, which prevent a drinking driver
      from operating a vehicle, are in use in the United States and Canada. Currently
      available studies indicate that interlocks reduce impaired driving recidivism
      while on the vehicle. However, in the United States, the practical effectiveness
      of these devices is limited because few offenders are willing to install them in
      order to drive legally. This paper reports on a study of a court policy that
      created a strong incentive for impaired driving offenders to install interlocks
      by making penalties (e.g., jail or electronically monitored house arrest) the
      alternative to the interlock. Comparison of the recidivism rates of offenders
      subject to this policy with offenders in similar, nearby courts not using
      interlocks indicated that the policy was producing substantial reductions in DUI
      recidivism.

PMID- 12214358
TI  - Binge drinking, sensible drinking, and abstinence after alcohol-related vehicular
      crashes: the role of intervention versus screening.
AB  - Brief interventions have been shown to reduce problem drinking in a variety of
      populations and settings. The hypothesis for our randomized trial was that
      individuals injured in alcohol-related crashes who received a more intensive
      intervention (brief counseling) would have reduced binge drinking as compared to
      those with a less intensive intervention (simple advice) and controls. Non
      alcohol dependent, seriously injured individuals (N = 186) were enrolled in the
      protocol. At baseline, mean binges/month (b/m) were 5.88 and at 12 months were
      2.02 b/m. Although there was no significant difference by condition, at 12 months
      the brief counseling group had the lowest rate of binge drinking (1.97 b/m).
      Whether these drinking patterns were a result of the crash, injury, screening for
      alcohol use, or combination of these factors is difficult to determine.

PMID- 12214359
TI  - Crash reconstruction and injury-mechanism analysis using event data recorder
      technology.
AB  - Sophisticated onboard crash-event data recorders (EDRs) that log key vehicle
      dynamics information can be used to improve crash reconstruction, model occupant
      response, study the mechanisms of injury, and estimate occupant injury
      probabilities in near-real time. Such an EDR was developed and utilized as part
      of the Automatic Collision Notification (ACN) system for the National Highway
      Traffic Safety Administration. This paper presents the results of a study in
      which the reconstruction of an actual crash was augmented using EDR/ACN-supplied
      three-dimensional acceleration and other data in a vehicle occupant model
      configured using the Articulated Total Body (ATB) computer code. ATB-generated
      occupant-motion imagery and body-region acceleration response information
      provided valuable insights that permitted crash-reconstruction specialists to
      ascertain the true nature of the collision and identify the probable cause of an
      injury suffered by one of the victims. The authors also posit that the use of EDR
      data from an ACN-type system as inputs to occupant crash-response modeling may be
      someday support crash-victim emergency medical treatment and triage.

PMID- 12214360
TI  - Crash protection for children in ambulances.
AB  - The objectives of the study were to determine the most effective and reliable
      means of restraining children on an ambulance cot and to develop recommended
      field procedures for emergency medical service providers. A series of crash tests
      at 48 km/h were conducted using convertible child restraints, car beds, and
      harness systems tested with 3-year, infant, and 6-year size dummies. Belt
      configuration and backrest position were varied. A new cot and fastener system
      significantly improved restraint performance over older systems previously
      tested. A two-belt attachment with elevated cot backrest was found to be the
      method with the least performance variability for securing either a convertible
      child restraint or a car bed. It was concluded that children who weight up to 18
      kg, fit in a convertible child restraint, and can tolerate a semi-upright seated
      position can be restrained in a convertible child restraint secured with two
      belts to an ambulance cot. Infants who must lie flat can be restrained in a car
      bed modified for two seatbelt paths and secured to a cot. In each case, the cot
      backrest must be elevated, and the cot and anchor system must be crashworthy.
      None of the harness configurations tested proved to be satisfactory, but an
      effective system could be developed by following accepted restraint design
      principles.

PMID- 12214361
TI  - The effect of road improvements on motor vehicle crash injury and mortality in a
      developing country.
AB  - The developing island-nation of Grenada undertook a major road improvement
      project between 1995 and 1998. In order to determine the effect of those
      improvements on crash injury and mortality, we reviewed the number of crash
      related injuries and deaths for the years 1994 and 1999. After the road
      improvements, the proportion of crashes that resulted in injury decreased from
      22% to 15%. The raw number of crashes (818 vs. 1233), deaths (4 vs. 12) and
      deaths per 100,000 population (4.1 vs. 11.9) increased, but the proportion of
      crashes that resulted in death (0.5% vs. 0.7%) remained effectively unchanged.

PMID- 12214362
TI  - Booster seats: a community based study of installation and use by parents and
      caregivers.
AB  - This paper describes characteristics of child safety seat misuse among attendees
      at 41 inspections held between February 1999-April 2001 in San Diego County, CA.
      Standardized criteria were assessed by certified technicians. These 41 events
      consisted of 988 inspections for proper installation and adjustment. 963 had a
      determined seat type (rear-facing, forward facing, belt positioning boosters,
      shield boosters, other restraint, vehicle safety belts). Each seat type had
      specific criteria for misuse ranging from 3 to 15 measures. 95.6% had at least
      one error, which could reduce the seat's protection of its occupant from injury
      in a crash.

PMID- 12214363
TI  - Motor vehicle occupant crashes among teens: impact of the graduated licensing law
      in San Diego.
AB  - To assess the effect of California's graduated driver's license (GDL) law in San
      Diego County, we compared motor vehicle crash and passenger injury rates
      involving 16-year-old drivers for 1999 and 2000, the first two years of the law,
      against 1997, using data from a statewide database of all injury crashes. While
      the crash rate per 1,000 drivers did not change following GDL, a significant
      decline in the percentage of 16-year-olds with a driver's license corresponded
      with large decreases in population-based crash and injury rates.

PMID- 12214364
TI  - Three year injury crash records of new licensees with suspensions or invalidity
      periods lasting 90 days or more.
AB  - A subset of new licensees, namely the ones with suspensions or invalidity periods
      of at least 90 days are studied. This subpopulation is comprised of 3,550 men and
      1,295 women for whom the study file contains age, gender, licensing exam
      performance, and the dates all police reported crashes for the first three years
      after licensing. This group is compared with the complementary subpopulation of
      53,069 men and 58,464 women. The average injury crash rate per year, not
      prorated, is 0.057 for men and 0.033 for women, about twice the rate for those
      without lengthy suspensions. These licensees are older, have lower success rates
      at licensing exams, and have a longer learning period than the others. Separate
      logistic-normal regression models for men and for women are estimated for the
      probability of a collision in a year using the available explanatory variables.

PMID- 12214365
TI  - Rear seating and risk of injury to child occupants by vehicle type.
AB  - The safety of rear-seated child passengers was evaluated across vehicle types.
      113,887 children under age 16 in crashes were enrolled as part of an on-going
      crash surveillance system which links insurance claims data to telephone survey
      and crash investigation data. Children in the second row suffered less
      significant injuries than those in the front in all vehicle types except compact
      extended cab pickup trucks in which the risk for children in the rear was 13% as
      compared to 2.8% for front-seated occupants. Further research is needed to
      identify the child and vehicle characteristics which might explain this increased
      injury risk.

PMID- 12214366
TI  - The effect of seating position on risk of injury for children in side impact
      collisions.
AB  - The objective of this study was to evaluate the effect of seating position on
      risk of injury to children in side impact crashes. 5,632 children under age 16 in
      side impact crashes were enrolled as part of an on-going crash surveillance
      system which links insurance claims data to telephone survey and crash
      investigation data. Children seated in the front seat were at higher risk of
      significant injury than children seated in the rear (OR = 2.2 95% CI (1.2-3.8)).
      After adjusting for age, restraint use, and vehicle damage, children in the front
      seat were more likely to be injured (OR 2.6 95% CI (1.1-6.2)) than children
      seated in the rear when the child was sitting near the side of the impact. These
      results highlight the importance of evaluating the safety performance of both
      vehicles and restraint systems for children in side impact crashes.

PMID- 12214368
TI  - Exposure-based death rates for child motor vehicle occupants.
AB  - We used reports of additional occupants on trips from the Nationwide Personal
      Transportation Survey to estimate travel in cars and trucks for children age nine
      years and younger. For children age five to nine years these indirect estimates
      were 98% of directly reported travel. Using this travel data, the death rate was
      4.0 per billion km of travel for children less than age one year and decreased to
      1.7 for children age nine years. Infants have a higher exposure-based death rate
      for travel in cars and trucks than older children despite greater restraint use.

PMID- 12214367
TI  - Male and female car drivers--differences in collision and injury risks.
AB  - Crash data from two UK resources were examined for differences between male and
      female passenger car drivers in collision circumstances and injury outcomes. The
      proportion of female car license holders is growing, women are more likely to be
      the driver in a collision and are more vulnerable to injury particularly neck
      strain. Women drive smaller, lighter cars compared to men and are more often the
      driver of the smaller vehicle in a multivehicle collision. Vehicle design, crash
      testing programmes and regulation, currently based heavily on the average male,
      should give more balanced consideration to female characteristics in future
      activities.

PMID- 12214369
TI  - Learning from experience. Interview by Paul Dinsdale.

PMID- 12214370
TI  - Made to measure. Interview by Charlotte Alderman.

PMID- 12214371
TI  - On the road.

PMID- 12214372
TI  - Team effort.

PMID- 12214373
TI  - Out of focus.

PMID- 12214374
TI  - Stop and think.

PMID- 12214376
TI  - Violence in A&E: the role of training and self-efficacy.
AB  - AIM: To determine the amount of violence experienced by a sample of A&E staff
      during a three-month period, and to explore the effect of aggression management
      training and exposure to violence on their self-efficacy in dealing with
      aggressive patients. METHOD: A small-scale questionnaire survey was undertaken of
      130 staff. RESULTS: 76 (58 per cent) responded. The findings suggested that
      verbal and physical violence were a common occurrence. The type and amount of
      aggression management training were variable. Greater self-efficacy in managing
      aggressive behaviour was observed in higher grades of staff, and in staff who had
      experienced higher levels of verbal aggression. CONCLUSION: Violence against
      nurses was widely reported. Their aggression management training did not appear
      to equip them with the skills required to manage this behaviour.

PMID- 12214377
TI  - Infection control policies in nursing homes.
AB  - The number of people living in nursing homes is increasing because of the ageing
      population. Older people are particularly vulnerable to infection, so it is
      important that infection control policies are drawn up for use in nursing homes.
      Staff need to be fully aware of such guidance and infection control should be
      incorporated into their everyday nursing practice. The author discusses
      information that should be included and gives advice on formulating policies.

PMID- 12214378
TI  - Indwelling urethral catheters.
AB  - Lesley Simpson discusses the risks associated with indwelling urethral catheters
      and identifies how nurses can reduce them with proactive management.

PMID- 12214379
TI  - Get moving.

PMID- 12214381
TI  - On the right trek.

PMID- 12214380
TI  - Life after back injury.

PMID- 12214382
TI  - Access is denied.

PMID- 12214383
TI  - Brief encounter. Interview by Daniel Allen.

PMID- 12214384
TI  - Survey of students from an eating disorders programme.
AB  - AIM: To survey former students of the English National Board N46 eating disorders
      programme at Anglia Polytechnic University, since its introduction in 1994.
      METHOD: This was a collaborative exercise involving lecturers and a former ENB
      N46 student, and provides a good example of evidence-based education. A postal
      questionnaire, consisting of questions relating to current employment,
      qualifications, evaluation of the ENB N46 and further training needs, was
      delivered to 45 former students, 27 of whom returned questionnaires. RESULTS: The
      analysis suggests that the ENB N46 programme had a significant effect on
      students' practice and continuing professional development, with 96 per cent of
      respondents saying they would recommend the course to others and 92 per cent
      indicating a clear commitment to continue working in this area. CONCLUSION:
      Specialist training courses in eating disorders represent a valuable contribution
      to the quality of client care and treatment, despite their scarcity and uneven
      distribution across the UK.

PMID- 12214385
TI  - Assessing community healthcare needs: lessons from Africa.
AB  - This article describes participatory approaches to needs assessments for
      community profiling in developing countries. It reviews the literature on
      compiling community profiles, provides an insight into conducting these in
      developing countries, and draws out lessons for those contemplating community
      profiling in the UK. The author's experience of primary health care in Africa
      shows that involving communities in the collection and analysis of data improves
      the value and quality of information, and the appropriateness of the programmes
      that result.

PMID- 12214386
TI  - Oxygen transport and the use of pulse oximetry.
AB  - Pulse oximetry is a useful way to monitor oxygen saturation in patients in a
      variety of clinical settings. Nurses need to understand the principles of oxygen
      transport and delivery to use pulse oximetry effectively in clinical practice.

PMID- 12214387
TI  - Round the clock.

PMID- 12214388
TI  - Flying by the seat of our pants.

PMID- 12214389
TI  - Let's get physical.

PMID- 12214390
TI  - Today's babysitters, tomorrow's parents. Interview by Charlotte Alderman.

PMID- 12214391
TI  - Demystifying HIV.

PMID- 12214392
TI  - Launching the Tidal Model in an adult mental health programme.
AB  - AIM: To implement a new model of psychiatric nursing that uses person-centred
      care to empower people with acute mental health problems. METHOD: A pilot study
      involved the introduction of the model into two wards in the acute mental health
      services in Newcastle City Health Trust. This was followed by introduction of the
      model into all nine adult acute wards in the service. One ward was evaluated for
      six months before and six months after introducing the model and nurses'
      perceptions of the model have been assessed using questionnaires. RESULTS:
      Preliminary findings of the ward evaluation show that since the model has been
      implemented, more people have been admitted on an informal basis and fewer have
      been subject to sections of the Mental Health Act (MHA); the number of admissions
      has doubled while the length of stay has decreased; violent incidents and
      episodes of self-harm have decreased; the use of restraint has decreased; and the
      interval between admission and assessment has decreased. Preliminary analysis of
      the nursing questionnaires shows positive perceptions of the model. CONCLUSION:
      The introduction of this model appears to have had a positive impact on the care
      being given to patients and the nurses using the model appear to be satisfied
      with the use of patient-centred care.

PMID- 12214393
TI  - Role of the nurse consultant in tissue viability.
AB  - Nurse consultant posts were introduced in 2000 with a view to expanding the role
      of nurses. The author was appointed as a nurse consultant in tissue viability to
      develop the service already in place in her trust and improve patient care. This
      article describes the role of the nurse consultant working in tissue viability
      and identifies the qualities and skills needed to undertake this role.

PMID- 12214394
TI  - Clean surgical wounds: prevention of infection.
AB  - Nurses need to be aware of the principles of infection control and the factors
      affecting wound infection to develop effective strategies to prevent infection
      and cross-infection.

PMID- 12214395
TI  - Going it alone.

PMID- 12214396
TI  - Reality check.

PMID- 12214397
TI  - Making up for lost time.

PMID- 12214398
TI  - New territory. Interview by Derek Hand.

PMID- 12214399
TI  - Healing old wounds.

PMID- 12214400
TI  - Falls in accident and emergency departments.
AB  - BACKGROUND: The records of 192 attendees at an accident and emergency department
      was audited. The aim of the audit was to identify the type of client at risk of
      falling, demography, fall events and medication history. CONCLUSION: The findings
      suggest that a more co-ordinated and integrated approach to assessment and
      treatment of older people could greatly reduce the occurrence of falling in these
      at-risk clients.

PMID- 12214401
TI  - The effect of recreational activities on older people's rehabilitation.
AB  - AIM: To explore the effect of a programme of recreational activities on older
      people undergoing a period of rehabilitation. METHOD: Following a exploration of
      quantitative methodologies, a qualitative approach was decided on. Face-to-face
      semi-structured interviews were conducted with six participants in a local
      patients' club. RESULTS: The analysis suggests that the stays in hospital were
      times of inactivity. In addition, social interaction was restricted by a
      combination of physical factors and the perception of a lack of staff time. The
      patients' club was identified as a stimulating and motivating force during the
      stay. However, it appeared to promote activity rather than social interaction.
      CONCLUSION: The patients' club was clearly beneficial to those who attended.
      However, while it filled the day, it did not address the issue of the limited
      social interaction that was the experience of the participants during their stay
      in hospital.

PMID- 12214403
TI  - Workplace wonders.

PMID- 12214402
TI  - Understanding benign breast disorders and disease.
AB  - Benign breast disorders can cause a lot of anxiety because of fears of cancer.
      The author gives an overview of different types of benign breast disorders and
      discusses appropriate treatment and management.

PMID- 12214404
TI  - [Comparison of demineralization of different organic acid to enamel].
AB  - The rates of demineralization of 5 organic acids (mathanoic acid, formic acid,
      propionic acid, Lactic acid, acetic acid, mixed acid) to the bovine enamel were
      tested and analysed with the self-made calcium ionselective
      microelectrodes(Ca(2+)-ISME) basing on a neutral carriers of ETH1001. The results
      showed; 1. The difference between the rates of demineralization of formic acid
      and lactic acid, formic acid and propionic acid, formic acid and acetic acid,
      acetic acid and mixed acid, acetic acid and lactic acid, propionic acid and mixed
      acid, propionic acid and lactic acid, lactic acid and mixed acid were of great
      significance (P < 0.01); 2. The rates of demineralization of acetic and mixed
      acid decreased with time, due to saturation of the solution during
      demineralization; 3. Ca(2+)-ISME was of the advantages of simplicity, rapidity,
      sensitivity and accuracy. The results suggest that the cariogenic potential is
      related to different acid products of different cariogenic bacteria, and the
      degree of mineral saturation within solution affects the rate of
      demineralization.

PMID- 12214405
TI  - [Research on inhibition of sodium fluoride on five subgingival bacteria in
      vitro].
AB  - This in vitro study was aimed at observing inhibition action of fluoride on 5
      common periodontal bacteria in subgingival microflora. The liquid media two-fold
      dilution method was used to determine the minimal inhibition concentration (MIC)
      of sodium fluoride (NaF) to 9 strains of bacteria representing the main
      periodontopathic species(P. gingivalis, A. actinomycetemcomitans, P. intermedius)
      and the periodontal beneficial species (S. sanguis) and 1 strain of S. sorbrinus.
      The results showed that all the bacteria were inhibited at different
      concentration of NaF. The MIC values ranged from 128 micrograms/ml for P.
      gingivalis and A. actinomycetemcomitans, 256 micrograms/ml for S. sorbrinus, 1024
      micrograms/ml for P. intermedius to 2048-4096 micrograms/ml for S. sanguis. The
      results suggest that NaF can also be used as a periodontal anti-bacterium agent
      and those preparations containing about 1000 micrograms/ml fluoride can be used
      effectively against the periodontopathic bacteria without disturbing the local
      ecological balance.

PMID- 12214406
TI  - [A study on anti-caries activity of genetic recombinant vaccine of Streptococcus
      lactis. II. Immunization in vein with recombinant S. lactis in pregnant rabbits].
AB  - The effects of immunization in vein with recombinant S. lactis HL107 carring the
      S. mutans surface protein PAc gene in pregnant rabbits were studied. The results
      indicated that specific anti-PAc IgG in serum and milk were obviously induced 1
      week after immunization and retained at high level for several weeks. It suggests
      that the recombinant S. lactis HL107 possessing immunogenicity of S. mutans
      surface protein PAc is able to stimulate specific systemic immune response
      against PAc.

PMID- 12214407
TI  - [The effects of fibronectin on the attachment and proliferation of periodontal
      ligament cells].
AB  - The purpose of this in vitro study was to observe and evaluate the effects of
      fibronectin(FN) on the growth of periodontal ligament cells(PDLC) on different
      root surfaces. Cell culture and scanning electronic microscopic techniques were
      used. The results showed that the growth pattern of PDLC on normal root surfaces
      were better than that of periodontitis. FN can significantly enhanced the
      attachment and proliferation of PDL cells on normal root surfaces. On the other
      hand, only the enhancement of attachment by FN was observed on the periodontitis
      root surfaces. It may be concluded that FN can promote the growth of PDLC and FN
      may play different effects on the attachment and proliferation of PDLC.

PMID- 12214408
TI  - [The study of changes of basement membrane in gingivae of adult periodontitis].
AB  - The major components of basement membrane including laminin and type IV collagen
      were studied by immunohistochemistry in 20 gingival specimens from patients with
      moderate to severe adult periodontitis and 10 normal gingival specimens combing
      with electron microscopic and PAS analysis. The results showed that laminin and
      type IV collagen were both present and stained with a continuous liner pattern in
      oral sulcular epithelium of the normal gingivae, while the pocket epithelial
      alterations of the periodontitis occurred, which included thinning, interruption,
      partial or complete absence of basement membrane involving one or more rete pegs
      and fragmentations. All these alterations may play an important role in the
      pathogenesis of adult periodontitis.

PMID- 12214409
TI  - [Inhibitory effects of 8-methoxypsoralen combining with all trans retinoic acid
      on oral squamous cancer cell lines].
AB  - To study the inhibitory effects of 8-methoxypsoralen (8-MOP) combining with all
      trans retinoic acid (RA) on tongue cancer cell line Tca8113 and gingiva cancer
      cell line Ca9-22, MTT assay (tetrazolium-based colormetric assay) was applied and
      the changes in morphology were observed with the inverted microscope. The results
      showed that with 30% growth inhibition of the cell lines, the Combination Indexes
      (CI30) of the two drugs were no more than 0.82, and with 50% growth inhibition,
      the Combination Index (CI50) were from 0.9 to 0.95, which indicated synergic
      combination effects of the two drugs against the two oral squamous cancer cell
      lines. Apoptosis-body-like structures were observed in the cells treated with RA,
      8-MOP, or the combination of RA with 8-MOP. Whether combination of the two drugs
      at appropriate concentrations has clinical value needs to be investigated.

PMID- 12214410
TI  - [The effect of internal irradiotherapy with 32P glass microspheres on tumor
      vasculature in mouse sarcoma 180].
AB  - In order to investigate the effect of internal irradiotherapy on tumor
      microvasculature, the vascular changes of tumor S180 following internal
      irradiotherapy with 32P glass microspheres were observed microscopically with
      vessel casts of resin perfusion and ink perfusion. The results showed that the
      microvessels expanded with the endothelial cells swelling and the amount of
      microvessels and new vessels decreased, which led to peritumoral vascular density
      descended. It suggests that internal irradiotherapy destroying the tumor
      microvasculature as external irradiation is an important influence on the
      efficiency of internal irradiotherapy.

PMID- 12214411
TI  - [Effect of taixian tablet on hamster buccal pouch carcinogenesis].
AB  - Eighty syrian hamsters were divided into 4 equal groups. The right buccal pouches
      of hamsters in group I and group II were painted three times weekly with 0.5%
      DMBA dissolved in acetone, but the hamsters in group I received 0.45 g Taixian
      tablet daily by mouth. The animals in group III only received 0.45 g Taixian
      tablet daily and group IV was control group. After 9, 12 weeks, animals were
      killed with their pouches excised, and tumors were counted and measured. The
      results showed; 1. Comparing with group II, the malignant rate of group I was
      lower after 9 weeks and the tumor volume was smaller after 12 weeks (P < 0.01);
      2. It was found histologically many inflammatory cells locating in the epithelial
      layer and lamina propria of group I after 9 weeks, while only a few inflammatory
      cells in group II. The high differentiated squamous cell carcinoma could be seen
      in group I and group II after 12 weeks, but no abnormal changes in cervical
      lymphnodes and organs (lung, liver, spleen, et al) of all animals in 4 groups. It
      suggests that Taixian tablet can restrain the development of oral carcinogenesis.

PMID- 12214412
TI  - [Effects of pregnancy on orthodontic tooth movements: effects of progesterone on
      orthodontic tooth movements in pregnant rats].
AB  - This study evaluated the periodontal responses and progesterone changes to
      orthodontic tooth movements in pregnant rats. Adult female Sprague-Dawley rats
      were separated into two groups: non-pregnant and pregnant. All rats were treated
      with fixed orthodontic appliances that moved the upper incisors in a distal
      direction during 10 days. At the end of the experiment, the periodontal tissues
      were examined histologically and immunohistochemically (ABC method). The results
      showed that in the histological examination of the tension sides of the upper
      incisors, the bone formation was more obvious in the pregnant group than that in
      the non-pregnant group. In the immunohistochemical staining, the osteoblasts were
      positive-stained cells and they exhibited deeper stain and higher percentage in
      the pregnant group. In a conclusion, the progesterone influences the periodontal
      reconstruction on orthodontic tooth movements in pregnant rats and may be helpful
      in alveolar bone formation, which suggests that orthodontic treatments in
      pregnant patients may not be so harmful as people thought before.

PMID- 12214413
TI  - [The distribution of nitric oxide synthetase in Vcx and its relation with the
      expression of FOS induced by teeth movement in rats].
AB  - It was studied the central role of nitric oxide(NO) during experimental teeth
      movement and the relation between nitric oxide synthetase (NOS) positive neurons
      and FOS like immunoreactivity (FLN) with the NADPH-diaphorase histochemistry and
      immunocytochemical reaction method. Results indicated that NOS positive neurons
      and FLN showed typical distribution in Vcx and there was some overlap between
      them. It suggests that NO is involved in the central modulation of the
      stimulating message of teeth movement, and which further explains the central
      modulation mechanism of experimental teeth movement in rats.

PMID- 12214414
TI  - [Determination of linear sintering shrinkage rate of slip-casting infiltrated
      ceramic].
AB  - This study tested the linear sintering shrinkage (SS) rate of ceramic infiltrated
      with different glasses (Vita In-ceram, G I-I La, G I-II La, G I-II Ce), the
      results showed that the linear SS rate was 0.08%-0.32%, which occurred mainly in
      the firing stage of alumina (P < 0.05) and glass infiltration had no influences
      on the dimensional stability of ceramic(P > 0.05). It suggests that the effects
      of glass infiltration on the dimensional stability of GI glasses were comparable
      with that of Vita In-ceram.

PMID- 12214415
TI  - [Quantitative study of catecholamines in normal human dental pulp].
AB  - The purpose of this report was to study quantitatively the levels of
      catecholamines in human dental pulp by high-performance liquid chromatography
      (HPLC). 10 healthy teeth were selected from the extractions due to orthodontic
      reasons. The pulp of the teeth were obtained immediately after the extraction and
      samples were analyzed by means of HPLC for levels of dopamine, epinephrine and
      norepinephrine. The result showed that the concentration of norepinephrine in
      human dental pulp was 23.47 +/- 0.52 micrograms/g pulp tissue and dopamine was
      19.17 +/- 1.03 micrograms/g pulp tissue.

PMID- 12214416
TI  - [Clinical pathology study of lingual carcinoma treatment with CDDP-AMS
      microcapsules through lingual artery].
AB  - 11 patients with lingual carcinoma were treated by artery chemoembolization with
      100 mg CDDP-AMS microcapsules (CDDP 13.6 mg) through lingual artery, and the
      average diameter of microcapsules was 56.3 microns. There was no obvious
      carcinoma cell or carcinoma tissue in pathologic specimens of the tissue after 4
      weeks of treatment. After 5-6 weeks of chemoembolization, the clinical tumor
      ulcer disappeared, but it was difficult to judge the change of the tumor because
      of local fiber tissue. After 6 months, by observation of 4 patients whose tumors
      had not been excised, it was found that the infiltuation mass of primary
      carcinoma disappeared and tongue body became soft. It suggests that artery
      chemoembolization with CDDP-AMS microcapsules is an efficient way of lingual
      carcinoma treatment.

PMID- 12214417
TI  - [Clinicopathological analysis of 15 cases of desmoplastic ameloblastoma].
AB  - 15 cases of desmoplastic ameloblastoma (DA) were studied clinicopathologically,
      which was combined with literature review of 50 cases. The results showed that
      the morbidity of DA was low, which occupied 7.4% of the whole ameloblastoma. The
      DA tumor occurred preferentially in anterior parts of the jaw and the maxillary
      bone, which exhibited radiographically a mixed radiolucent-radiopaque appearance,
      and the main pathological characteristic was extensive fibrous hyperplasia in
      stroma and scattering epithelial nests with different sizes. Some cases showed a
      mixture type of DA and classical ameloblastoma.

PMID- 12214418
TI  - [Histologic study on the pulpal response after complete crown preparation].
AB  - Protecting pulp health during preparation procedures is one of the key factors
      for prosthesis success. The histological sections of dental pulp showed the
      disruption of odontoblastic layer, blood vessels hyperemia and local bleeding.
      Dental histological sections of 40 healthy teeth which would need to be detracted
      because of orthodontical treatment were made to observe the pulp response in vivo
      during different tooth preparation time, including four groups: before
      preparation, after preparation, one week after being covered with temporary crown
      and two weeks after being covered with temporary crown. when air-water spray was
      used during crown preparation, Healing of the pulp was apparent 2 weeks following
      preparation, when the prepared teeth were covered with temporary crown and
      cemented with zinc oxide eugenol.

PMID- 12214419
TI  - [Clinical analysis of traumatic herniation of buccal adipose body].
AB  - Traumatic herniation of buccal adipose body is not rare, but available clinical
      data are not sufficient and nomenclature has not been standardized. 11 clinical
      cases of traumatic herniation of buccal adipose body and 1 typical cases were
      reported, and nomenclature and classification of the disease were discussed
      combining with relevant references. Finally, it suggests the diagnosis and
      therapy of traumatic herniation of buccal adipose body.

PMID- 12214420
TI  - [Study on the biosynthesis of para-aminobenzoic acid by S. sanguis. I.
      Establishment of a reversed-phase high-performance liquid chromatography].
AB  - In order to study the synthesis of para-aminobenzoic acid (PABA) by S. mutans and
      the role of PABA in the interaction between S. mutans and S. sanguis, a reversed
      phase high-performance liquid chromatography (RP-HPLC) for analysis of PABA was
      developed. The results showed that the optimal chromatographic parameters were
      flow rate of 1.5 ml/min, T = 55 +/- 2 degrees C, methanol/phosphate buffer of
      10/90(by vol) (pH 2.2 0.1 mol/L), m-hydroxybenzoic acid as an internal standard.
      The method is simple, rapid accurate and useful.

PMID- 12214421
TI  - [Study on the biosynthesis of para-aminobenzoic acid by S. sanguis. II.
      Qualitative and quantitative analysis].
AB  - In this study, the method established in paper 1 was used to analyze PABA
      synthesized by S. sanguis S34. The results showed: 1. S. sanguis S34 did
      synthesize PABA and the mean concentration of PABA was 1.236 micrograms/ml. 2.
      the components had good linear relation and average recovery was 80%. The results
      of this paper will be helpful to studying influencing factors on PABA synthesis
      of S. sanguis and the roles of PABA in microbial homeostasis of dental plaque.

PMID- 12214422
TI  - [Stability of HA-coated titanium implants used as orthodontic anchorage].
AB  - 12 two-stage HA-coated titanium implants were inserted into the mandibular
      alveolar bones of two dogs were loaded with orthodontic force of 150 gram for 3
      months. The stability of the implants under orthodontic force were studied with
      intraoral and radiographic examinations. The results showed that both intraoral
      and radiographic analysis were reliable for assessing implant stability, and no
      signs of fixture dislocation were found during the force application period (P >
      0.05), while the abutment was tilted after being loaded for 2 to 3 months. This
      suggests that HA-coated titanium implants remain stable enough under orthodontic
      force and are suitable as anchorage for short-term orthodontic therapy after
      design of the implant neck is improved.

PMID- 12214423
TI  - [Preliminary study on HA-coated titanium implants used as anchorage for
      protraction of dog molar teeth].
AB  - HA-coated titanium implants were placed surgically into dog mandible to protract
      the mandibular second molars with an orthodontic force of 150 g. During the force
      application period of 3 months, the movement of the molars was tested
      periodically and relevant reasons of movement were analysed. The results showed
      that the mesial moving distances of the second molar were respectively 1.04 mm,
      1.68 mm and 1.76 mm at the first, second and third month, and the main reason of
      tooth mobility was ascribed to the implant anchorage. It can be concluded tiat HA
      coated titanium implant can be used as anchorage for moving and fixing posterior
      teeth in the orthodontic treatment.

PMID- 12214424
TI  - [Assessment of marginal tissue around HA-coated titanium implants for orthodontic
      anchorage in dogs].
AB  - 12 two-stage HA-coated titanium implants placed in dogs' mandibles were loaded
      with an orthodontic force of 150 g for 3 month. Gingival bleeding index, plague
      and calcucus index, mobility index, probing depth and marginal bone were
      investigated. The results showed that the implants were stable and peri-implant
      soft tissue displayed slight inflammation, but no marginal bone absorption and no
      difference of bone quantity between the tension side and compression side were
      found. It can be concluded that the clinical trials of marginal tissue around the
      HA-coated titanium implants are satisfactory when the implants are used as
      anchorage for short-term orthodontic treatment.

PMID- 12214425
TI  - [Induction of insulin-like growth factor I expression to mandibular advancement
      in growing rat condylar cartilage].
AB  - It was studied effects of functional mandibular advancement on IGF-I peptide of
      condylar cartilage of 60 5-week-old male rats. Animals were randomly divided into
      the experimental and control groups, and the mimic functional appliances were
      used in experimental group. The rats were killed after 1, 3, 7, 14, 21 and 28
      days. The results showed that the condylar cartilage of growing rats expressed
      IGF-I the strongest in the germinal layer, medial in the transitional layer, and
      the least in the maturational layer. IGF-I positive cells and their
      immunoreactive levels increased after 1 week of functional mandibular
      advancement, and reached the peak level at 2 weeks. The results suggest IGF-I in
      mandibular condyle of rat is related to its growth and differentiation activity,
      and changes of condylar IGF-I after functional protrusion are relevant to the
      histologic changes and cellular functions which indicate their involvement with
      active bone growth and remodeling.

PMID- 12214426
TI  - [Differential expression of IGF-I and its mRNA in mandibular condylar cartilage
      of rat--direct evidence for servosystem theory of facial growth].
AB  - It was studied the expression of IGF-I and its mRNA in the condylar cartilage of
      10 7-week-old SD male rats by using in situ hybridization and immunohisto
      chemistry technique. The results showed both IGF-I and its gene expressed in
      growing rat condyle. IGF-I peptide was abundant in germinal zone, and positive
      reaction of its mRNA was strongest in transitional and maturational zones. These
      indicate that condylar cartilage has the capability of local production and
      secretion of IGF-I, mediating the command effect of STH, and differential
      expression of IGF-I and its mRNA might establish the local feedback loop, which
      supply a direct evidence for servosystem theory of facial growth.

PMID- 12214427
TI  - [SEM study of machinable vita cerec mark II porcelain surface morphology after HF
      acid etching].
AB  - After HF acid etching under 5 different HF concentrations and 6 exposing times,
      the surface morphology of machinable porcelain was examined by scanning electron
      microscope, and the porsosity percentage and ething depth were determined. The
      results showed that the etching depth increased with the rising of HF
      concentration and disposing time until 5%-7.5 min. The porosity percentage of
      ething surface was positively interrelated with HF concentration and disposing
      time. It was the first time to classify the etching patterns of machinable
      porcelain into four groups.

PMID- 12214428
TI  - [Shear bond test of HF acid etching machinable porcelain bonded to enamel with
      different concentration and disposing time].
AB  - After HF acid etching under 5 different HF concentrations and 6 exposing times,
      shear bonding strength of porcelain to enamel were tested. The results showed
      that HF acid etching technique had a positive influence on the bonding strength
      of porcelain to enamel. The most favorable concentration-time groups were 2.5%
      5.0 min, 5.0%-5.0 min, 7.5%-2.5 min, 10.0%-1.0 min, 15.0%-0.5 min, and the
      debonding type of porcelain-resin-enamel composite body was mixed debonding.

PMID- 12214429
TI  - [Facial soft tissue features analysis of normal Han race adults in Guangdong
      Province using computer-assisted-photogrammetric-system].
AB  - Facial soft tissue profile features of 150 normal native adults of Guangdong
      Province were analysed using computer-assisted-photogrammetric-system, which
      contained parameters written by polar coordinate. The results indicated that
      normal native adults of Guangdong Han race showed sex and region difference in
      features of facial profile soft tissue, and those parameters written by polar
      coordinate were helpful in the further study and clinical therapy.

PMID- 12214430
TI  - Introduction to the Special Section on Cognitive Science and Psychological
      Assessment.
AB  - This introduction to the Special Section on Cognitive Science and Psychological
      Assessment begins with a brief overview of cognitive science and its interface
      with the clinical assessment of cognitive functioning. Concepts and themes
      permeating the articles in this section are then taken up. Included are cognitive
      model architectures and model parameters, differential emphasis on efficiency
      versus content of cognition, and implementation of stochastic and dynamical
      aspects of cognitive processes. Selected distinguishing attributes of the
      respective contributions are highlighted.

PMID- 12214431
TI  - Assessing clinically relevant perceptual organization with multidimensional
      scaling techniques.
AB  - Multidimensional scaling (MDS) techniques provide a promising measurement
      strategy for characterizing individual differences in cognitive processing, which
      many clinical theories associate with the development, maintenance, and treatment
      of psychopathology. The authors describe the use of deterministic and
      probabilistic MDS techniques for investigating numerous aspects of perceptual
      organization, such as dimensional attention, perceptual correlation, within
      attribute organization, and perceptual variability. Additionally, they discuss
      how formal quantitative models can be used, in conjunction with MDS-derived
      representations of individual differences in perceptual organization, to test
      theories about the role of cognitive processing in clinically relevant phenomena.
      They include applied examples from their work in the areas of eating disorders
      and sexual coercion.

PMID- 12214432
TI  - A contribution of cognitive decision models to clinical assessment: decomposing
      performance on the Bechara gambling task.
AB  - The Bechara simulated gambling task is a popular method of examining decision
      making deficits exhibited by people with brain damage, psychopathology,
      antisocial personality, or drug abuse problems. However, performance on this task
      is confounded by complex interdependencies between cognitive, motivational, and
      response processes, making it difficult to sort out and identify the specific
      processes responsible for the observed behavioral deficits. The authors compare 3
      competing cognitive decision models of the Bechara task in terms of their ability
      to explain the performance deficits observed in Huntington's disease patients as
      compared with healthy populations and people with Parkinson's disease. The
      parameters of the best fitting model are used to decompose the observed
      performance deficit of the Huntington patients into cognitive, motivational, and
      response sources.

PMID- 12214433
TI  - Using connectionist models to guide assessment of psychological disorder.
AB  - Connectionist models are introduced as promising tools for understanding the
      nature of psychological disorders and guiding their assessment. Specifically,
      ways in which connectionist models can guide the following aspects of the
      assessment process are described: understanding what constructs are relevant to
      assess, designing approaches to assessing these constructs, and understanding
      individual differences in data from assessments. Two extended examples are given
      based on the authors' research on cognitive aspects of depression and Alzheimer's
      disease.

PMID- 12214434
TI  - Application of stochastic modeling to the assessment of group and individual
      differences in cognitive functioning.
AB  - This article begins with a guiding schema of relations among cognitive science,
      clinical science, and assessment technology. Emphasis is placed on stochastic
      modeling of cognitive processes. Basic models are adjusted so as to
      parsimoniously accommodate performance deviations occurring with psychopathology.
      Modified portions of models indicate functions affected by disorder, whereas
      portions remaining intact indicate spared functions. Findings from clinical
      cognitive science are applied to the individual case using Bayesian procedures.
      Methods are instantiated with respect to cognitive psychopathology of paranoid
      schizophrenia. The authors address observations and issues arising from this
      application, including integration of these methods with current assessment
      practices.

PMID- 12214435
TI  - Trajectory of cognitive science and psychological assessment: current status and
      expectations.
AB  - Salient commonalities and distinctions of the set of contributions to this
      special section are synthesized and discussed. The examination provides a
      springboard for observations on future developments in cognitive-science
      applications. Issues considered include imminence and nature of clinical
      implementation, prediction of selected client transactions outside the assessment
      context, integration with complementing modes of clinical assessment, and
      reciprocal information sharing by clinical and nonclinical cognitive scientists.

PMID- 12214436
TI  - An afterword: the utility of cognitive models for the field of psychopathology.
AB  - Cognitive models of psychopathology provide opportunities and challenges for both
      the research psychopathologist and the clinician concerned with practical
      applications to individuals. Heterogeneity of individual pathology within
      diagnostic categories, heterogeneity of content within symptom categories, undue
      reliance on judgment-based ratings, and frequent emphasis on deficit rather than
      the overt behavior of the patients are some of the major issues. Others include
      the complex interaction between cognitive and affective processes and the fact
      that input-output functions are often nonlinear and marked by critical threshold
      values for the appearance of overt pathology. An important feature of models is
      the discipline that they introduce into theorizing about psychopathology plus the
      focus on precise quantification.

PMID- 12214437
TI  - MMPI-A scores and high points of male juvenile delinquents: scales 4, 5, and 6 as
      markers of juvenile delinquency.
AB  - The Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A) clinical,
      supplementary, and content scale score patterns for 655 male delinquents were
      examined. Low scores on Scale 5 (Masculinity/Femininity) were found to be the
      most frequent deviation, followed by elevations on Scales 6 (Paranoia) and 4
      (Psychopathic Deviate). This is consistent with previous research, although the
      importance of Scale 5 deviations has been little noted because of the traditional
      focus on scale elevations only. Classification analysis indicated that a
      combination of MMPI-A scales discriminated between this delinquent sample and the
      normative sample, with a sensitivity of 90%-95% and a specificity of 80%-85%.
      This level of sensitivity was maintained in a replication sample (N = 473).

PMID- 12214438
TI  - A Variable Response Inconsistency scale and a True Response Inconsistency scale
      for the Millon Adolescent Clinical Inventory.
AB  - Variable Response Inconsistency (M-VRIN) and True Response Inconsistency (M-TRIN)
      scales were developed for the Millon Adolescent Clinical Inventory using 104 male
      and 78 female delinquents, ages 13-17 years. M-VRIN efficacy was assessed by
      comparing nonrandom protocols of 76 male and 34 female delinquents, ages 13-17
      years, with 100 computer-generated random protocols. Nonrandom protocols were
      screened using a matched-pair Minnesota Multiphasic Personality Inventory
      Adolescent or Jesness Inventory. M-TRIN efficacy was assessed by comparing
      protocols with 160 simulated acquiescent and nonacquiescent protocols.
      Specificities of .95 or higher showed sensitivities up to .89 for M-VRIN, and .90
      and .79 for M-TRIN. Predictive power and overall effectiveness are reported for
      several base rates. Small relationships may exist between M-VRIN and race, and
      between M-TRIN and gender.

PMID- 12214439
TI  - Children's internal representations, empathy, and fantasy play: a validity study
      of the SCORS-Q.
AB  - The authors investigated relationships among internal representations, empathy,
      and affective and cognitive processes in fantasy play to test the validity of the
      Social Cognition and Object Relations Scale Q-Sort (SCORS-Q; D. Westen, 1995)
      with children. Eighty-six 8-10-year-olds were administered 8 Thematic
      Apperception Test cards, a standardized play task, and a self-report empathy
      measure. Teachers rated children's empathy and helpfulness. As predicted,
      internal representations were related to empathy, helpfulness, and quality of
      fantasy play. Developmental differences on the SCORS-Q were consistent with
      object relations theory and with results from the original SCORS. The findings
      support the value of internal representations as a means of understanding
      children's interpersonal functioning and contribute to the validity of the SCORS
      Q for use with children.

PMID- 12214440
TI  - Measuring stress resilience and coping in vulnerable youth: the Social Competence
      Interview.
AB  - A brief interview to measure stress coping capabilities was developed and tested
      in 4 samples of African American and White adolescents in low-income
      neighborhoods of 2 large U.S. cities. The Social Competence Interview (SCI) is a
      10-min social stressor that assesses physiological and social-emotional responses
      to a recurring real-life problem. A new behavioral coding system using audiotapes
      permits reliable and valid assessment of components of social competence,
      including Interpersonal Skills (expressiveness, empathy), Goal-Oriented Strivings
      in coping (self defense, social acceptance, competitiveness, stimulation
      pleasure, approval, self improvement), and Social Impact (high vs. low
      affiliation/control). High SCI expressiveness and self-defensive striving create
      a critical-aggressive social impact, which is correlated with increased hostility
      and anger.

PMID- 12214441
TI  - Do desirability ratings moderate the validity of probability ratings on the
      Smoking Consequences Questionnaire-Adult? A reanalysis using regression.
AB  - Smokers' responses to the Smoking Consequences Questionnaire-Adult (A. L.
      Copeland, T. H. Brandon, & E. P. Quinn, 1995) were used to determine whether
      smoking outcome expectancies are moderated by subjective evaluations
      (desirability ratings) in their effect on smoking-related variables. Hierarchical
      regression in a reanalysis of data from A. L. Copeland et al. indicated that the
      product of probability and desirability ratings accounted for a significant
      amount of variance in smoking rate, nicotine dependence, saliva cotinine, and
      posttreatment smoking status above that accounted for by probability and
      desirability ratings alone. Results indicate that desirability ratings serve as
      moderators to probability ratings in explaining current smoking, nicotine
      dependence, and continued smoking. Effects were modest in magnitude but suggest
      that it may be important to address subjective evaluations of outcomes in smoking
      cessation and relapse prevention efforts.

PMID- 12214442
TI  - Two-subtest estimations of WAIS-III factor index scores.
AB  - The reliability and validity of various short forms of the Wechsler Adult
      Intelligence Scale-Third Edition (WAIS-III; D. Wechsler, 1997) were evaluated in
      a sample of 100 patients with traumatic brain injury and in a demographically
      matched subgroup from the standardization sample. All short forms were based on 2
      subtest estimations of the respective factor indexes. Although acceptable
      estimates could be obtained from all short forms for Verbal Comprehension, none
      of the possible short forms for Perceptual Organization consistently met the
      minimum criterion regarding the percentage of cases that fell within the 90%
      confidence interval of the full-length index. It is concluded that short-form
      estimates of the WAIS-III are not appropriate for clinical use when the goal is
      to obtain factor indexes.

PMID- 12214443
TI  - The multidimensional structure of perfectionism in clinically distressed and
      college student samples.
AB  - Confirmatory factor analysis was used to evaluate 2 multidimensional measures of
      perfectionism (R. O. Frost, P. Marten, C. Lahart, & R. Rosenblate, 1990; P. L.
      Hewitt & G. L. Flett, 1991). On a first-order level, support was found for Hewitt
      and Flett's (1991) original 3-factor conceptualization of perfectionism, although
      only for an empirically derived 15-item subset. Support was also obtained for 5
      of the 6 dimensions proposed by R. O. Frost et al. (1990), but the model only
      displayed good fit when a refined scale containing 22 of the original 35 items
      was used. A second-order analysis found evidence for 2 higher-order factors of
      adaptive and maladaptive perfectionism. Perfectionism dimensions correlated in
      expected directions with personality domains, symptom distress, and academic
      achievement. The brief measures of perfectionism also retained the construct
      related validity displayed by the full-item versions.

PMID- 12214444
TI  - [Initial steps are completed].

PMID- 12214445
TI  - [Fitness in the elderly].
AB  - A healthy way of growing old is supposed to postpone for as long as possible the
      physiological loss of functional organ capacity and preserve a high quality of
      life. While the individual predisposition depends on genetic variables,
      behavioral and environmental influences have a strong modulating effect on the
      aging process. According to our current knowledge, there is no doubt that
      physical fitness prolongs life and prevents cardiovascular diseases in
      particular. Physical activity and sports have many positive effects, which are
      well proven. In addition to the cardiovascular system, bone metabolism and immune
      status should be mentioned here. Furthermore, the increase in quality of life
      through physical training is undisputed, with positive effects for persons of any
      age. Current data prove that regular moderate training provides the greatest
      benefits.

PMID- 12214446
TI  - [Prevention and complementary medicine in aging].
AB  - The subsequent brief review is based on a systematic literature search (Medline,
      http://www.lef.org and books under the topic Antiaging from 2001). Among the
      preventive and complementary measures against aging, caloric restriction with an
      adequate diet is in first place. If the energy supply is reduced by 17%,
      cardiovascular mortality drops to 31-41%. Among the mechanisms of aging, impaired
      formation of reactive oxygen species (oxidative stress) plays an important role.
      Moreover, antioxidants (vitamins A and B as well as selenium) provide protection.
      If obesity is complicated by a metabolic syndrome, a formula diet should be
      employed under the supervision of the urologist. The hormonal changes involved in
      the male climacteric should be treated by hormone replacement therapy.
      Testosterone given as a gel, plaster, or injection compensates for the secondary
      hypogonadism and treats osteoporosis. The muscle function can be improved by
      physical activity only. Sexual dysfunction, however, is not corrected with
      androgen hormone replacement therapy, whereas an appropriate physical training
      program may even improve potency by inducing a reactive penile hyperemia. In his
      office the urologist may implement a program specifically for the "aging male."
      If he diagnoses a metabolic syndrome, effective countermeasures are required to
      prevent early onset of arteriosclerosis.

PMID- 12214447
TI  - [Kidney transplantation in the elderly].
AB  - As the number of both elderly patients suffering from end-stage renal disease and
      of elderly donors is increasing, Eurotransplant has started the Eurotransplant
      Senior Program (ESP). New strategies for treatment of patients who need dialysis
      and improved screening methods allow renal transplantation even in elderly
      patients. Improved immunosuppressive protocols for older recipients lead to
      higher patient survival rates and improved quality of life.

PMID- 12214448
TI  - [Urogenital infections in the elderly].
AB  - The increasing incidence of asymptomatic bacteriuria and symptomatic urinary
      tract infections in the elderly requires a detailed consideration of this problem
      including age-specific medical and social risk factors. The increasing need for
      care, age- and gender-related complicating factors such as subvesical
      obstruction, adnexal infections, and incontinence, and the need for
      catheterization are predominant. Specific age-related diseases such as diabetes
      mellitus, pharmacodynamic alterations of antimicrobial substances, and changes in
      the vaginal colonization make increased demands on therapeutic strategies.
      Urologic implications resulting from this set of difficulties have not yet been
      investigated sufficiently and need further evidence-based work-up.

PMID- 12214449
TI  - [Tumors in the elderly].
AB  - The prevalence and incidence of cancer are age related; increased longevity thus
      increases the number of elderly patients with cancer. Only a few data suggest
      that en bloc radical cystectomy in patients with bladder cancer and radical
      prostatectomy in patients with prostate cancer can be safely performed on
      properly selected elderly patients (aged 70 years or older) with results
      comparable to those for younger patients. Due to the physiologic decline in renal
      function and hepatic drug metabolism in old age, chemotherapeutic agents show
      increasing toxicity in the elderly. The elderly remain underrepresented in
      clinical trials. In the absence of comprehensive data on treatment in the
      elderly, the belief persists that the elderly derive less benefit and suffer
      greater toxic effects from chemotherapy than younger patients.

PMID- 12214451
TI  - [Obstruction of the lower urinary tract].
AB  - Vital aging is difficult to define; however, most people would agree that vital
      aging is something desirable. Voiding problems are frequent in the aging
      population. Obstruction of the lower urinary tract is often the cause of these
      problems with subsequent impact on the general quality of life. Etiologic and
      pathophysiologic investigations not only focus on the prostate itself but also on
      the interaction between prostate, bladder, and sphincter apparatus and the
      regulation of the voiding process. Correlation to other disorders as well as
      therapeutic aspects and issues of sexual function and quality of life are only
      some issues on the "to do" list in an aging population. A proper patient
      selection for therapy and a mobilization of the symptomatic patient will also be
      important targets in the future.

PMID- 12214450
TI  - [Incontinence in the elderly].
AB  - Due to the continuing increase in the share of elderly people in our population,
      dysfunctions of the lower urinary tract, often involving urinary incontinence or
      urinary retention, are becoming more and more widespread. The prevalence of age
      related urinary incontinence is approximately 30% and occurs in women twice as
      often as in men. Multiple morbidity, multiple medication, age-related immobility,
      as well as a reduction of cerebral performance are cofactors, which can have a
      negative impact on urinary storage and micturition. An additional aspect is the
      aging process of the bladder and the sphincter as well as their central control
      mechanisms. As yet too little is known about this aging process. The complexity
      of age-related urinary dysfunctions requires specific strategies with respect to
      diagnostics and therapy, differing from strategies applied in younger patients.
      In order to decide on the best possible treatment, it is important to consider
      the sex of the patient, the degree of patient compliance, the question of whether
      he is looked after at home or in an institution, the feasibility of the therapy,
      and finally, to make a realistic estimation of the improvement that can be
      expected in his quality of life.

PMID- 12214452
TI  - [Sexuality in the elderly].
AB  - Disturbance of sexual function and sexual perceptions in the aging often have a
      significant negative impact on overall quality of life. Epidemiological data on
      this phenomenon are sparse. Recently, however, more investigations have been
      undertaken to improve diagnostic and therapeutic approaches. First scientific
      concepts are now emerging that will allow better patients care in the future.

PMID- 12214453
TI  - [Urothelial carcinoma. Role of G-protein coupled receptors in cell movement and
      proliferation].
AB  - To develop new therapeutic strategies we examined the expression and
      signaltransduction of G protein-coupled receptors in a human transitional cell
      carcinoma cell line. The receptors for lysophosphatidic acid (LPA) and thrombin
      potently stimulate cell migration. Pretreatment with PTX completely inhibited
      cell motility induced by LPA. In the model of chemically induced bladder
      carcinoma in rats the effects of intravesical instillation of PTX or phosphate
      buffered saline was examined. The incidence of G2-G3 cells in cytology was
      significantly reduced in rats treated with PTX. To ascertain the side effects of
      intravesical instillation of PTX a Phase I study was initiated. 15 patients were
      instilled with PTX at 5 dose levels (14-72 micrograms/100 ml) 3 times a week.
      Instillation of PTX up to 72 micrograms was without local or systemic side
      effects. PTX is a substance which potently inhibits tumor cell motility and
      progression. Intravesical treatment was well tolerated and therefore, the
      influence of PTX on local tumor should be evaluated in a Phase II study.

PMID- 12214454
TI  - [Kidney calculus episode in a supernumerary 3rd kidney].
AB  - Supernumerary kidney is a rare renal anomaly. As a distinct encapsulated
      parenchymatous mass, this free accessory organ has a separate blood supply and
      excretory duct system. We report on a patient who presented with an acute episode
      of abdominopelvic pain, secondary to hydronephrosis of a third kidney, situated
      in the pelvis behind the bladder. Modern diagnostic methods assisted in the
      conservative management of this well functioning third kidney.

PMID- 12214455
TI  - [Isolated epididymal torsion in dissociation of testis-epididymis].
AB  - Complete dissociation of testis and epididymis is rare. An isolated torsion of
      the epididymis has not been reported so far. We report two cases: a 6-month-old
      boy who was admitted with fever and swollen hemiscrotum and an 18-year-old youth
      with acute onset of pain in the left hemiscrotum. Immediate inguinal surgical
      exploration of the baby showed a complete infarction of the epididymis due to an
      isolated epididymal torsion with dissociation of testis and epididymis.
      Epididymectomy was carried out and the testis was sutured down. In the case of
      the youth, the surgical exploration also showed an isolated epididymal torsion
      due to dissociation of testis and epididymis. The epididymis could be rescued by
      raising the torsion. The isolated torsion of the epididymis should be included in
      the differential diagnosis of acute scrotum in childhood.

PMID- 12214456
TI  - [Intravesical migration of a polypropylene mesh implant 3 years after
      laparoscopic transperitoneal hernioplasty].
AB  - The repair of an inguinal hernia is the surgical procedure most often performed.
      Complication rates after laparoscopic hernioplasty amount up to 19%, with
      hematoma/seroma, neuralgia, urinary retention, and chronic pain most frequently
      reported. Significant complications such as trocar site bleeding or bowel injury
      occur in 0.4-5.6%, and sporadic intraoperative lesions of the bladder have been
      mentioned. We present a 48-year-old patient with recurrent dysuria 3 years after
      transabdominal preperitoneal hernioplasty (TAPP). The preoperative diagnostic
      evaluation led to the assumption of an intravesical mesh dislocation. In spite of
      extensive adhesions between the mesh and the bladder wall, the mesh including
      five fixation coils could be removed via a suprapubic access. The postoperative
      period was without complications, and the patient has no complaints. The
      incidence of complications after laparoscopic hernioplasty is low. Still, severe
      problems such as mesh rejection, spermatic granuloma, or mesh migration into the
      small and large intestine do occur. Migration of a mesh into the urinary bladder
      has only been described twice.

PMID- 12214457
TI  - [Recommendations for permanent, interstitial brachytherapy alone in localized
      prostate carcinoma].

PMID- 12214458
TI  - [Diagnosis and therapy of testicular tumors].

PMID- 12214459
TI  - [Helicobacter pylori infection and gastric diseases--pathogenesis and effects of
      eradication].
AB  - H. pylori infection is associated with major gastroduodenal diseases, i.e. peptic
      ulcer, cancer and MALT lymphoma in the stomach. The pathogenesis of H. pylori in
      these diseases has been elucidated. Non-atrophic diffuse antral gastritis is
      correlated with duodenal ulcer and multifocal atrophic gastritis is correlated
      with both gastric ulcer and cancer. It is well known that Japanese tend to have
      multifocal atrophic gastritis. H. pylori eradication therapy dramatically reduces
      the recurrence rates of gastroduodenal ulcers in humans and bacterial eradication
      for peptic ulcer patients has been recommended in many countries. Mongolian
      gerbils have provided an excellent model of gastric carcinogenesis and H. pylori
      enhanced (promoted) chemical carcinogen-induced carcinogenesis in the stomach
      using this model. H. pylori eradication reduced the incidence of gastric cancer
      in the Mongolian gerbil model. It was a recently discovered that a transforming
      clone carrying the translocation t (11;18) (q21;q21) forms a MALT lymphoma, the
      growth of which is independent of H. pylori and will not respond to bacterial
      eradication. In the early stage, the tumor can be successfully treated by
      eradication, but at a later stage additional genetic abnormality in the lymphoma
      may show no response to H. pylori eradication therapy.

PMID- 12214460
TI  - [Latest information in the diagnoses of ovarian carcinoma].
AB  - Despite improvements in median and overall survival from a combination of
      improved operation techniques and chemotherapy with platinum-compounds and
      paclitaxel, long-term survival rates for patients with epithelial ovarian
      carcinoma remain disappointing, and ongoing efforts are aimed at developing more
      effective primary therapies. In early ovarian carcinoma, conservative management
      is used to denote surgery that preserves reproductive potential without
      compromising curability. With some exceptions, such a strategy may be applicable
      for women younger than 40, who wish to bear children. A major dilemma facing
      gynecologic oncologists is to determine whether the accurate staging laparotomy
      is needed for apparent low-risk stage I ovarian carcinoma and how many cycles of
      chemotherapy will be needed for high-risk stage I ovarian carcinoma. In advanced
      ovarian carcinoma, main objectives of salvage therapy include: a improvement in
      quality of life and symptoms; b. tumor load reduction and survival advantage; c.
      evaluation of potentially active new drugs to be included in first-line
      treatment. We need to evaluate the potential benefit on survival of systematic
      pelvic and para-aortic lymphadenectomy during primary or secondary cytoreductive
      surgery in patients with advanced ovarian carcinoma. Paclitaxel/cisplatin is
      considered to be the international standard treatment based on the data of GOG
      111 trial showing that paclitaxel/cisplatin has provided a survival benefit
      better than that of cyclophosphamide/cisplatin. This choice of standard therapy
      might, however, be questioned based on the results of the largest randomised
      study, ICON3. There were no statistically significant differences in progression
      free or overall survival among paclitaxel/carboplatin and carboplatin only or a
      platinum combination (cyclophosphamide/doxorubicin/cisplatin). The best selection
      for adjuvant chemotherapy is still controversial and a large number of studies
      are now ongoing.

PMID- 12214461
TI  - [Treatment of malignant ovarian germ cell tumor and sex cord tumors].
AB  - We outline chemotherapy mainly for malignant ovarian germ cell and sex-cord
      tumors, based on studies in the literature and our own clinical experiences. With
      both tumors, PEB treatment is standard adjuvant chemotherapy. With regard to the
      number of dosage courses, 4 courses are regarded as tolerable after incomplete
      reduction, and 3 courses as adjuvant treatment after complete extraction. This
      chemotherapy is effective for preservation of fertility in young patients with
      malignant ovarian germ cell tumor. In both tumors, some cases show chemotherapy
      resistance. An effective second-line treatment strategy using a new anticancer
      agent needs to be established for such cases in the future.

PMID- 12214462
TI  - [Gestational trophoblastic tumors and recent clinical information].
AB  - Recent clinical advances in the field of gestational trophoblastic diseases are
      described. WHO modified its risk factor scoring system. This change was proposed
      to combine both the basic FIGO anatomic staging with the modified WHO risk factor
      scoring system. Patients who score as low-risk are treated with single agent
      chemotherapy, such as methotrexate (MTX), and patients refractory to MTX are
      treated with a combination chemotherapy, EMA/CO. Patients who score as high-risk
      are treated with EMA/CO, and patients refractory to the first line chemotherapy
      may be successfully treated with EP/EMA. Recent epidemiological data showed that
      women with complete hydatidiform moles could anticipate normal reproduction in
      the future. Studies found that pregnancies after treatment of molar pregnancy
      resulted in 69% full-term, live births; 8% premature deliveries; 1% ectopic
      pregnancies, and 0.5% stillbirths. First-trimester spontaneous abortions occurred
      in 17% of pregnancies, and major and minor malformations were detected in 0.4% of
      infants. Patients with hydatidiform mole were at increased risk of developing
      molar pregnancy in subsequent conceptions. After having one molar pregnancy, the
      risk of having molar disease in a future gestation was about 1%. The risk of
      persistent gestational trophoblastic tumors was increased by long-term oral
      contraceptive use before conception. In a large, multicenter, case-control study,
      the risk was shown to be increased in women who had ever used oral
      contraceptives, but was highest for women taking oral contraceptives during the
      cycle in which they became pregnant. Partial hydatidiform moles were never
      previously proven to transform into choriocarcinoma; however, a recent study with
      molecular techniques clearly showed that partial moles could transform into
      choriocarcinoma. All patients with suspected partial moles should be reviewed
      centrally and require hCG follow-up.

PMID- 12214463
TI  - [Latest information of therapeutic approach for endometrial cancer].
AB  - The role of chemotherapy for metastatic endometrial carcinoma is palliation,
      although modest response can be achieved because of development of chemotherapy.
      The response rate is 31-56% of conventional CAP therapy and 33-81% of AP therapy.
      However these chemotherapeutic regimen did not prolong the survival. Recently, a
      randomized trial of TAP therapy (TXL 160 mg/m2 3 h, day 2, ADM 45 mg/m2, day 1,
      CDDP 50 mg/m2 day 1) versus AP therapy (ADM 60 mg/m2, CDDP 50 mg/m2) was
      reported. The response and survival of TAP is superior to that of AP. Taxane will
      be key drugs for chemotherapy of endometrial cancer in the future.

PMID- 12214464
TI  - [Latest information on the treatment of uterine cervical cancer].
AB  - We investigated the role of hemoglobin level in chemoradiation therapy for
      patients with advanced cervical cancer by reviewing the literature for current
      therapeutic information. We found that anemia during chemoradiation therapy is an
      important physiological factor in determining the long-term prognosis of patients
      with advanced cervical cancer.

PMID- 12214465
TI  - [Treatment of vulvar cancer--updated information].
AB  - Over the past 20 years, the management of vulvar cancer has changed dramatically.
      The radical vulvectomy that was previously believed to be the only effective
      treatment for vulvar cancer has now been replaced by more individualized
      treatments. These include conservative surgery for patients with isolated
      lesions, omission of groin lymph node dissection in T1A tumors with stromal
      invasion < 1 mm, elimination of routine pelvic lymphadenectomy, groin lymph node
      dissection with separate groin incision, omission of contralateral groin lymph
      node dissection in T1 tumor with negative ipsilateral node metastasis, use of
      preoperative radiotherapy to avoid pelvic exenteration in advanced cases, and
      postoperative radiotherapy to decrease the incidence of groin recurrence in
      patients with multiple positive groin nodes. In addition to these changes, the
      identification of sentinel lymph nodes and chemoradiation therapy are currently
      under investigation. In this review, we discuss these issues along with the
      evidence upon which these therapies are based.

PMID- 12214466
TI  - [Phase I study of biweekly paclitaxel and carboplatin administration in patients
      with advanced non-small cell lung cancer].
AB  - A phase I study of a biweekly outpatient regimen composed of carboplatin (CBDCA)
      and paclitaxel (TXL) was conducted for advanced non-small cell lung cancer. TXL
      was given in combination with a fixed dose of CBDCA (AUC 3) every 2 weeks. The
      starting dose of TXL was 100 mg/m2, and the dose was escalated in increments of
      20 mg/m2. Three to six patients were allocated to each level. Toxicities were
      evaluated in the first 4 courses to determine the maximum tolerated dose (MTD).
      TXL 160 mg/m2 dosages proved to be MTD, and the dose limiting toxicity (DLT) was
      hematotoxicity (neutropenia). The patients, however, recovered from neutropenia
      using G-CSF immediately, when G-CSF was used. Gastrointestinal toxicity was well
      tolerated. A response was found in 9 out of 20 patients who received 4 courses or
      more (45%). These results suggest that the recommended dose would be CBDCA (AUC
      3) + TXL 140 mg/m2. The biweekly regimen has a high level clinical activity and
      excellent tolerability, and is suitable for outpatients. We started a phase II
      study because of these results.

PMID- 12214467
TI  - [Significance of tissue PyNPase, TS, and DPD activities in breast cancer].
AB  - We analyzed the interim results of prognostic significance of pyrimidine
      nucleoside phosphorylase (PyNPase), thymidylate synthase (TS), and
      dihydropyrimidine dehydrogenase (DPD) in 5-FU-based chemotherapy for breast
      cancer. In surgical specimens of tumor tissues and normal mammary gland tissues
      from 102 breast cancer patients, TS, PyNPase, and DPD activities were measured,
      and p53 and c-erbB-2 overexpression were also examined. TS, d-Thd-Pase/Urd-Pase
      (PyNPase), and DPD activities were significantly higher in tumor tissues than in
      normal tissues. There was a strong correlation between d-Thd-Pase and Urd-Pase in
      tumor tissues. No relationship was found between patient characteristics and any
      of the enzyme activities. PyNPase activities were significantly higher in the
      tissues having a c-erbB-2 overexpression of 75% (4+) or more than in those having
      less than 75%, and the tissues with a p53 of 50% (3+) or more had significantly
      higher TS activities than those with less than 50%. However, the other parameters
      showed no significant difference. The data obtained so far suggest no clear
      correlation between the activity of any of these enzymes and prognosis.

PMID- 12214468
TI  - [A new regimen for TS-1 therapy designed to minimize adverse reactions by
      introducing a one-week interval after each two-week dosing session].
AB  - It has been reported that the response rate to TS-1 of advanced recurrent gastric
      cancer was the highest rate (46.5%) of effectiveness among anti-cancer agents,
      but the incidence of adverse reactions to this drug has been found to be as high
      as 83.2%, with grade 3 or severer reactions occurring in 20.3% of patients.
      Taking into consideration the post-marketing survey finding that adverse
      reactions to the drug first appear 2-3 weeks after the start of oral TS-1
      therapy, we attempted a new dosing regimen for this drug, wherein each session of
      therapy lasted for 2 weeks, with a one-week interval between two consecutive
      sessions (herein-after called "the 2-week regimen"). This regimen was employed
      based on the expectation that the adverse reactions to the drug would be
      minimized and that the consecutive dosing period could be prolonged, while
      keeping the anti-cancer potency at a level similar to that expected with the 4
      week dosing regimen with a 2-week interval between sessions (the 4-week regimen).
      The subjects were 38 patients with advanced or recurrent stomach cancer who were
      treated with TS-1 at our center between September 1999 and November 2001. Twenty
      four patients treated using the 4-week method until January 2001 were taken as a
      historical control, and compared with 14 patients treated using the 2-week method
      from February 2001 and afterwards. The incidence of adverse reactions was 71% in
      the 2-week regimen group against 92% in the 4-week regimen group. The incidence
      of grade 3 or severe adverse reactions was 8% in the 2-week group and 21% in the
      4-week group. Thus, the incidence of adverse reactions was lower in the 2-week
      group. The percentage of patients who complied with the dosing instructions
      completely during a 6-month period, as evaluated by the Kaplan-Meier method, was
      86% in the 2-week group and 58% in the 4-week group. The response rate, as
      calculated in patients whose lesions could be evaluated, was 25% in the 2-week
      group and 19% in the 4-week group. These results suggest that the 2-week regimen
      may allow safer outpatient drug therapy using TS-1 and merits a trial when
      considering the QOL of patients. We propose conducting a phase-II multi-center
      clinical study of this regimen in the near future.

PMID- 12214469
TI  - [Second cancer after starting treatment for prostate cancer].
AB  - The subjects for the present study were 270 patients with prostate cancer who
      underwent initial treatment at our hospital over the 14 years from 1986 to 1999.
      They were investigated to assess the relationship between their treatment and
      metachronous tumors. Sixteen patients (5.9%) developed cancer of other organs
      after starting treatment for prostate cancer. These metachronous tumors included
      gastric cancer in six patients as well as lung cancer, esophageal cancer,
      colorectal cancer, liver cancer, renal cancer, bladder cancer, skin cancer,
      leukemia, and mediastinal adenocarcinoma. Treatment for prostate cancer other
      than surgery included radiotherapy in eight patients, administration of
      estramustine phosphate sodium in nine patients, and LH-RH analogues in six
      patients. The chi-square test showed no significant difference in the incidence
      of metachronous cancer in relation to the presence/absence of these three
      therapies. The present study therefore ruled out the possible induction of other
      tumors by treatment for prostate cancer.

PMID- 12214470
TI  - [A case of advanced esophageal cancer with multiple lymph node metastases
      successfully treated with induction chemotherapy consisting of nedaplatin and 5
      FU followed by chemoradiotherapy].
AB  - A 61-year-old male patient had esophageal carcinoma with multiple mediastinal and
      right supraclavicular lymph node metastases. Chemotherapy consisting of infusion
      of nedaplatin and continuous infusion of 5-fluorouracil was performed. After
      three courses of the chemotherapy, the patient was treated with a combination of
      cisplatin and 5-FU and radiotherapy. However, only radiotherapy was performed
      after 18 Gy because of grade 3 leukocytonenia during the chemoradiotherapy. The
      patient achieved a partial response (nearly complete response) for 9 months after
      the initiation of the treatment. In conclusion, chemotherapy with NDP and 5-FU
      followed by chemoradiotherapy is effective and safe for patients with esophageal
      carcinoma with multiple lymph node metastases.

PMID- 12214471
TI  - [A case of residual gastric cancer accompanied by esophageal invasion in which
      residual lesions were eradicated by half-dose administration of TS-1].
AB  - The patient was a 64-year-old male. On November 21, 1991, he underwent gastric
      resection on the pyloric side for early gastric cancer in the authors' hospital,
      and did not experience recurrence for many years thereafter. However, endoscopic
      examination of the upper gastrointestinal tract performed on June 11, 1999
      revealed advanced cancer in the posterior wall of the residual stomach which was
      accompanied by invasion of the esophagus. Thus, the residual stomach was
      completely removed on July 5, 1999. The histopathological findings were tub1, se,
      ly3, v2, aw(-), ow(+) and ew(+), and a portion of the esophageal stump and the
      serosa of the lesser curvature were positive for cancerous tissue. Endoscopic
      examination was performed one month after the operation, on August 7, 1999. A
      forceps biopsy taken from an elevated lesion of the esophagus at the posterior
      wall of the anastomosis revealed adenocarcinoma cells in the lower layer of the
      squamous epithelium. A residual esophageal lesion was thus diagnosed. Beginning
      on August 9, 1999, TS-1 was administered in a dosage of 50 mg bid, but it was
      later learned that the patient had ingested only half of that TS-1 dosage (i.e.,
      50 mg/day). After completion of one course of this therapy, endoscopy was again
      performed. It was found that the prominence on the esophageal mucosa at the
      anastomosis, which had been diagnosed as being cancerous tissue, had shrunk in
      size, while a forceps biopsy taken from the same site yielded no findings of
      malignancy. The patient was followed for 18 months thereafter, and endoscopy was
      performed three times during that interval but continued to yield no evidence of
      malignancy. As of February 2001, this patient had completed 12 courses of TS-1 at
      one-half its usual dosage. There have been no findings of recurrence, and the
      patient's course continues to be good. In summary, this was an interesting case
      in which residual cancer was detected in the esophageal stump following resection
      for gastric cancer, and it can be concluded that TS-1 therapy was effective in
      spite of being incomplete (i.e., half-dose), eradicating the residual cancer
      tissue.

PMID- 12214472
TI  - [A case of gastric carcinoma with metastasis in a paraaortic lymph node that
      responded to TS-1/CDDP combination therapy, in which the patient was able to
      undergo extirpation with grade B curability].
AB  - Since the introduction of TS-1 for the treatment of gastric carcinoma, an overall
      high response rate of cancer to TS-1 therapy has been recognized. Therefore, TS-1
      in combination with cisplatin (CDDP) can be reasonably expected to be an
      effective new strategy for the treatment of advanced gastric carcinoma. We
      administered three courses of the TS-1/CDDP combination in a case of gastric
      carcinoma with metastasis in a paraaortic lymph node. Regression of the primary
      carcinoma (72.7% decrease in tumor mass) and reduction in size of the lymph node
      were observed. Consequently, the patient underwent total gastrectomy, resection
      of the splenic arterial trunk, splenectomy and D3 lymph node dissection, which
      resulted in grade B curability. The state of the patient was favorable both at
      the time of surgery and postoperatively, and the course of therapy remained
      uneventful. Although grade 1 nausea and vomiting were noted as adverse reactions
      to the treatment resulting in insufficient oral intake and necessitating
      intravenous infusion in the hospital, the treatment was completed without any
      other adverse events during the course of the therapy.

PMID- 12214474
TI  - [Three patients with advanced nonresectable and recurrent gastric cancer
      responding to chronomodulation chemotherapy with tegafur + cisplatin + isovorin
      followed by CPT-11 administration].
AB  - Today, no effective chemotherapy regimen has been established for non-resectable
      or postoperative recurrent gastric cancer, and most such therapy seems to be
      palliative. Thus, a highly effective chemotherapy that allows good patient QOL is
      desired. We report three gastric cancer patients responding to chronomodulation
      chemotherapy (tegafur + cisplatin + Isovorin) based on circadian rhythms plus a
      new antitumor drug, CPT-11. The treatment protocol was tegafur 1,200 mg/body,
      days 1-12 (continuing 16 h, intravenously with 800 mg/body from 16 to 24 h, 400
      mg/body from 24-8 h, for non-uniform administration), cisplatin 10 mg/body, days
      1-5, 8-12, (16 h, one shot infusion), Isovorin 25 mg/body, days 1-5, 8-12 (16 h,
      one shot infusion), followed by CPT-11 100 mg/body, days 13 (one shot infusion).
      We performed 1 or 2 courses, and with 2 courses the CPT-11 dose was increased to
      150 mg/body. The first patient was a 54-year-old female with advanced type 3
      gastric cancer with liver metastasis (H3). After chemotherapy (2 courses), there
      was a 30% reduction in the advanced gastric cancer and a 95% reduction in the
      liver metastasis. The second patient was a 73-year-old male with recurrent type 1
      gastric cancer in the remnant stomach 24 months after partial gastrectomy. After
      chemotherapy (1 course), there was a 45% reduction in advanced gastric recurrent
      cancer. The third patient was a 67-year-old male with advanced type 2 plus 3
      gastric cancers with liver (H3) and abdominal lymph node metastases. After
      chemotherapy (1 course), there was a 70% reduction in the type 2 and 55%
      reduction in the type 3 advanced gastric cancer, and a 50% reduction in the liver
      metastasis and 35% reduction in the abdominal lymph node metastasis. The only
      adverse effect was grade 2 pancytopenia, gastrointestinal disorder, and alopecia.
      In conclusion, this regimen resulted in good intrachemotherapeutic QOL and was
      highly effective in advanced gastric cancer patients.

PMID- 12214473
TI  - [A case of gastric cancer with paraaortic lymph node metastasis responding to TS
      1/CDDP as neoadjuvant chemotherapy].
AB  - A 64-year-old male visited our hospital with complaints of epigastric pain.
      Computed tomography (CT) showed gastric cancer with extensive paraaortic lymph
      node metastasis. We decided that a curative operation was impossible, and
      administered the following chemotherapy. After 120 mg/day of TS-1 was orally
      administered for 3 weeks followed by 2 drug-free weeks with 90 mg of CDDP was
      administered intravenously on day 8, CT showed a 90.6% reduction in the
      paraaortic lymph node metastasis. No serious adverse reaction was observed. After
      2 courses of this chemotherapy, surgery was performed after informed consent was
      obtained from the patient. Histrogical result showed PR. The patient is now
      healthy and no sign of recurrence has been observed. TS-1/CDDP therapy is useful
      for advanced gastric cancer.

PMID- 12214475
TI  - [A new combination therapy with low-dose FP and daily oral administration of low
      dose etoposide--a report of 2 cases].
AB  - We report 2 patients with advanced gastric cancer treated with a new combination
      chemotherapy of low-dose FP and daily oral administration of low-dose etoposide.
      Patient 1 was an 84-year-old man. He was diagnosed with cancer of the remnant
      stomach with multiple liver metastases. For eight months, he was treated as an
      outpatient and his performance status (PS) stayed at stage 1. Patient 2 was a 67
      year-old man with lymph node metastasis of the lung. For the first 6 weeks, he
      was treated under hospitalization and for the following 10 months he was treated
      as an outpatient. His PS remained in stage 1 and blood CEA value fell from 2,420
      ng/ml to 46.9 ng/ml. Upper gastrointestinal series showed a recovery of the
      extension of his lower gastric body. Both cases were so-called prolonged NC. From
      the viewpoint of patient QOL, this new combination is a possible candidate for a
      more effective chemotherapy.

PMID- 12214476
TI  - [A case of multiple skin metastases from gastric cancer successfully treated with
      docetaxel combined with doxifluridine].
AB  - The results of treatment of gastric cancer with docetaxel have scarcely been
      reported. Combination chemotherapy of docetaxel and doxifluridine was
      administered to five patients with recurrent or unresectable gastric cancer in
      the authors' department, and the overall response rate was 40%. Among them, we
      report here a case of multiple skin metastases successfully treated with this
      chemotherapy. A 71-year-old man had already undergone total gastrectomy with
      splenectomy about one year previously because of advanced gastric cancer: type 3,
      tub2, se, n1, INF gamma, ly3(+), v1(+), stage IIIa. He was treated with adjuvant
      chemotherapy of low-dose FP (CDDP/5-FU) for two weeks, and thereafter 5-FU (200
      mg/day orally) was administered. Skin metastases appeared on the right upper
      eyelid and the left femoral region, though no recurrent findings were detected by
      CT, US, and the like one year after operation. The combination chemotherapy of
      docetaxel and doxifluridine was administered because multiple skin tumors rapidly
      appeared on the back and the right upper eyelid region. These tumors disappeared
      after 3 weeks and he has had no recurrence more than one year after chemotherapy.

PMID- 12214477
TI  - [Two cases of stage IV type 4 gastric cancer with good response to TS-1].
AB  - We report two patients with Type 4 gastric cancers having multiple lymph node
      metastasis and carcinomatosa which responded well to TS-1. After administration
      of TS-1 orally for two courses, both patients showed improved extension of the
      gastric wall and almost complete reduction of metastatic lymph nodes. In case 2,
      colonic stenosis due to peritonum carcinomatosa disappeared after chemotherapy
      with TS-1. Total gastrectomy was performed in both patients in accordance with
      their wishes. It was confirmed histopathologically that TS-1 was effective
      against the primary sites and lymph node metastasis. Both patients are well
      without recurrence and continue taking TS-1.

PMID- 12214478
TI  - [Complete response in a case of recurrent gastric cancer treated with TS-1].
AB  - We report the case of 72-year-old man with recurrent gastric cancer who was
      successfully treated with TS-1. We performed only non-curative operation because
      the tumor had infiltrated the pancreas head and aspiration pneumonia
      complications developed under the anesthetic. Abdominal CT revealed local
      recurrence and metastasis of the paraaortic lymph node after 3 months, so we
      started TS-1 chemotherapy. One course consisted of daily oral administration of
      100 mg TS-1 for 4 weeks and withdrawal for 2 weeks. The recurrent lesions
      disappeared completely after 1 course. Furthermore, this therapy was continued
      for 3 courses without any side effects.

PMID- 12214479
TI  - [A case of recurrent gallbladder cancer responding to low-dose 5-FU and CDDP
      therapy].
AB  - We treated a patient with a postoperative local recurrence of gallbladder cancer
      who showed a long-term response to low-dose 5-fluorouracil (5-FU) and cisplatin
      (CDDP) therapy. A 60-year-old woman was diagnosed with advanced gallbladder
      cancer, for which she underwent an extended cholecystectomy, bile duct resection
      and a partial resection of the duodenum in March 2000. The pathological diagnosis
      was well differentiated tubular adenocarcinoma of si, ly1, v1, hinf2, binf2, n0.
      Eight months later, she presented with cholangitis and obstructive jaundice due
      to a local recurrence of the gallbladder cancer and her serum CA19-9 level had
      increased to 1,991.6 U/ml. The biliary obstruction was treated by PTCD and a
      subsequent self-expanding metallic stent. In addition, she was also placed on
      combined chemotherapy with low-dose 5-FU and CDDP. Her serum CA19-9 level
      thereafter gradually decreased, so that after eight months it was within the
      normal range, and the recurrent tumor at the hepatic hilus was also observed to
      have decreased in size on the CT scan. As of this writing she has undergone eight
      courses of low-dose 5-FU and CDDP therapy over about a year and has been able to
      maintain a good quality of life without any severe adverse effects.

PMID- 12214480
TI  - [CPT-11 hepatic arterial injection plus oral UFT administration for liver
      metastasis of rectal cancer--report of two cases].
AB  - The first patient was a 51-year-old male who had 5-fluorouracil-resistant
      recurrent rectal cancer with multiple liver metastases. He was given our new
      combination chemotherapy consisting of hepatic arterial injection of CPT-11 (20
      mg/body) on day 1 and day 2 and oral administration of UFT (300 mg/day) on days 3
      to 6 of a 7 day cycle starting in January 2001. Six weeks after the beginning of
      chemotherapy, the liver metastatic lesions were reduced. He is now living with
      outpatient treatment. The second patient was a 76-year-old male who had initial
      recurrent rectal cancer with multiple liver metastases. Thirty-two weeks after
      the same chemotherapy, the metastatic lesions had completely disappeared. Twelve
      months have passed since this chemotherapy, and we have not found any recurrent
      tumor. While significant antitumor effects were observed, there were few adverse
      events in either patient. These results suggest that combined chemotherapy of CPT
      11 by hepatic arterial injection and oral administration of UFT is an effective
      treatment for liver metastases of rectal cancer.

PMID- 12214482
TI  - [Identification of common disease related genes by means of genome-wide SNP
      typing].
AB  - Determination of the human genome sequence will enable analysis of one entire set
      of genes (genome). Single nucleotide polymorphism (SNP) is now increasingly a
      focus of attention because of its important role in the genetic background of
      common disease. In Japan, we have identified 190,000 SNPs in two years and also
      established high-throughput genotyping system as part of SNP projects started in
      2000. Using such infrastructure, we are now advancing to the next phase:
      identification of common disease-related genes by genome-wide association
      studies.

PMID- 12214481
TI  - [Long-term complete response to treatment with TS-1 in a patient with
      oropharyngeal squamous cell carcinoma].
AB  - A 60-year-old man had a recurrence of squamous cell carcinoma at the right side
      of the tongue base. Chemotherapy with TS-1 (100 mg/day) was begun. Each course of
      chemotherapy consisted of 4 weeks of TS-1, followed by 2 weeks of no treatment.
      After the completion of two courses, macroscopic examination revealed a complete
      response. From the third course of TS-1 treatment, the dose was increased to 120
      mg/day. The complete response persisted on macroscopic examination. A biopsy done
      during the ninth course of TS-1 treatment confirmed the complete response
      histologically, with no evidence of malignancy. After 12 courses of TS-1
      treatment, the drug was switched to 600 mg/day of UFT. Although there were no
      signs or symptoms of recurrence, the patient died of cancer of the pancreas.
      There was no recurrence of the oropharyngeal cancer, even at the time of death.

PMID- 12214483
TI  - Sexually transmitted diseases in Maryland teens.

PMID- 12214484
TI  - The psychosocial issues and stigmatization of lesbian and gay adolescents.

PMID- 12214485
TI  - Teen pregnancy in Maryland. State and local coalition development.

PMID- 12214486
TI  - An overview of substance abuse in adolescents.

PMID- 12214487
TI  - Tobacco use among adolescents.

PMID- 12214488
TI  - Drug of choice: the dangerous effects of teen alcohol use.

PMID- 12214489
TI  - The real health problem of Maryland's youth: where the bodies are hidden.

PMID- 12214491
TI  - Strangers in a strange land ... decoding adolescents.

PMID- 12214490
TI  - Guns and gunshot wounds among teens are an epidemic.

PMID- 12214492
TI  - Adolescent sports medicine.

PMID- 12214493
TI  - A review of obesity in adolescence.

PMID- 12214494
TI  - Adolescent immunizations.

PMID- 12214495
TI  - The adolescent with asthma: strategies for improved outcomes.
AB  - Asthma is a chronic disease that affects millions of Americans. Evaluation and
      treatment guidelines have been developed by panels of experts for over 10 years.
      Management of the teen with asthma, however, creates special opportunities for
      the practitioner, because of the transition of adolescents from dependence on the
      family to an increased desire for independence. This article will review our
      current understanding of the special needs of the adolescent asthmatic, and make
      recommendations for improving disease control.

PMID- 12214496
TI  - Art, artists, and arthritis.

PMID- 12214497
TI  - Medical training in the United States in the pre-Civil War era: the formation of
      medical schools.

PMID- 12214499
TI  - Adolescence.

PMID- 12214498
TI  - Cost and effectiveness: approval and payment for Pulverizer.

PMID- 12214501
TI  - [Concepts of development of the neurosurgical operative environment in the 21st
      century].
AB  - The operative environment has to a large extent defines the "state of the art and
      science" of neurosurgery, which is now undergoing rapid reinvention. In order to
      remain current, each neurosurgeon should periodically reconsider their personal
      operative environment and its functional design with reference to modernity of
      practice as currently defined. Historical trends and their analysis offer
      predictive guides for development of such settings with an eye toward the future.
      Examination of technical developments in decade timeframes defines the progress
      in capability and need. Progressive minimalism of manipulation and the presence
      of operative definition with increasing precision are evident, with concurrent
      miniaturization of attendant computerized support systems, sensors, robotic
      interfaces, and imaging devices. These trends and developments offer the
      opportunity for simplificity of setting design with higher functionality as the
      desired endpoint.

PMID- 12214500
TI  - Adolescent medicine: an introduction.

PMID- 12214502
TI  - [Surgical treatment of meningiomas of the craniovertebral junction].
AB  - The results of surgical treatment in 21 patients with meningiomas of the
      craniovertebral junction are presented. Main clinical diagnostic criteria in
      relation to the site of a tumor relative to the brain stem are considered. The
      basic surgical approaches used in the surgical treatment of meningiomas of the
      craniovertebral junction are described. These include posterior, median,
      posterolateral, transcondylar approaches. Surgical techniques to remove
      meningiomas having a matrix of varying areas were concretized, this is also done
      in relation to the consistency of a tumor. The outcomes of surgical treatment are
      analyzed. Possible postoperative complications and measures of their prevention
      and treatment are considered.

PMID- 12214503
TI  - [70th anniversary of the Moscow Institute of Neurosurgery: history and present].

PMID- 12214504
TI  - [Access to the anterior cranial fossa through the frontal sinus].
AB  - In 1998 to 2001, the Academician N. N. Burdenko Research Institute of
      Neurosurgery operated on 15 patients aged 20 to 65 years who had bulky processes
      in the base of the skull and paranasal sinuses by applying an access through the
      frontal sinus. Most patients (n = 7) had meningiomas. The others had osteoma of
      the base of anterior cranial fossa (n = 2), chondroma (n = 2), angiofibroma (n =
      1), fibroma (n = 1), esthesioneuroepithelioma (n = 1), and neurinoma (n = 1). The
      main criteria for choosing this access were the site and extent of a process, the
      sizes of the frontal sinus, and no signs of acute or chronic rhinosinusitis. The
      length of frontal sinuses in the most measurement was 3.5 to 5.0 cm, their width
      was 7 to 10 cm. All patients showed no progression of neurological symptoms.
      Three patients had a decrease in visual acuity from 1.0 to 0.8; with vascular
      therapy, visual disorders regressed during 2 months. Olfaction became worse in 4
      cases, there was anosmia in 2 cases. Nasal liquorrhea was not observed. When
      there were tumors in the anterior cranial fossa, an access through the anterior
      wall of the frontal sinus permits radical removal of both intra- and extracranial
      parts of a tumor with closure of the defect with a periostal flap.

PMID- 12214505
TI  - [Neurotransplantation in the treatment of Parkinson disease: follow-up].
AB  - The paper presents the results of follow-up of 11 patients with Parkinson's
      disease (PD) after neurotransplantation (NT) of fetal brain dopaminergic
      suspension into the caudatus and putamen on one or two sides. All the patients
      were clinically assessed at least 3 months before and during a follow-up (for as
      long as 9 years) in accordance with the Core Assessment Program for Intracranial
      Transplantation (CAPIT) by a Russian group of the Network of European CNS
      Transplantation and Restoration (NECTAR) Programme by using the Unified
      Parkinson's Disease Rating Scale (URDRS). An analysis of clinical findings showed
      that: 1) there was a slight amelioration in bradykinesia, rigidity, and smaller
      dosage of L-DOPA; 2) tremor and drug-induced dyskinesia remained unchanged; 3)
      subsequently (till 9 years), the clinical effect slightly decreased in almost all
      patients with PD and in some of them the clinical status became worse than that
      prior to surgery; 4) repeated NT (2 cases) in the striatum contralaterally did
      not improved the situation; 5) only neurostimulation of subcortical structures
      improved clinical results. So we can conclude that NT alone cannot be beneficial
      and requires additional interventions at the subcortical level.

PMID- 12214506
TI  - [Some problems of nontraumatic nasal rhinorrhea].
AB  - The paper outlines some issues of nontraumatic nasal liquorrhea. The authors
      state that in the vast majority of cases, liquorrhea occurs along the passage of
      olfactory filaments through the perforated lamina. Their morphological studies
      provide indirect evidence for this statement. Encephalomeningocele through the
      perforated lamina of the ethmoid bone or Turkish saddle is much more infrequent
      cause of liquorrhea. The authors have developed 2 methods of surgical treatment:
      1) endonasal closure of a fistula and 2) its intracranial closure. With mode 1,
      the nasal mucosa in the upper nasal passage and roof is destroyed and muscle
      tamponade is made. This method was used to operate on 66 patients. Liquorrhea
      recovered in 13 patients. It is less traumatic and less expensive and less
      effective. With method 2, trepanation is made in the frontal region, the dura
      mater is dissected, the olfactory bulb is destroyed and the site of the
      perforated lamina is tamponed with a muscle tissue piece. A total of 23 patients
      were operated on, a good result was achieved in 22 patients of them. Subsequently
      liquorrhea did not restore in any case. The method is more traumatic, but more
      effective. With method 3, if liquorrhea occurs through the Turkish saddle, the
      procedure to close a fistula corresponds to endonasal plasty, only the site of
      fistular destruction is the sphenoid sinus. The tip of an aspirator is inserted
      through the aperture of the sinus, its mucosa is destroyed, thereafter it is
      tamponed with a muscle flap. Three patients were operated on. Liquorrhea ceased.

PMID- 12214507
TI  - [Water electrolyte disorders in the postoperative clinical picture of basal
      diencephalitic tumors].
AB  - The paper deals with the relationship of homeostatic and motivational disorders
      in the postoperative clinical picture in basal-diencephalic tumors. The material
      included 354 clinical observations of: hypophysial adenoma (n = 135);
      craniopharyngioma (n = 71); tumors of the third ventricle (n = 88); basal
      meningiomas (n = 60). A comparative analysis of the findings allowed the authors
      to support that there are typical variants of changes in the patients' status,
      which reflect the nature of ion-osmotic disorders. The most significant mental
      disorders were transient hyperosmolar-hypernatriemic disturbances. The poor
      predictors were persistent hypernatriemia concurrent with evolving coma, systemic
      hemodynamic and respiratory disorders. Hyponatriemia is a better predictor of
      ionosmotic disorders, which requires a careful postoperative monitoring and a
      comparison of its findings with the specific features of intensive care
      performed.

PMID- 12214508
TI  - [Role gene expression changes in development of human brain gliomas].
AB  - The identification and characterization of genes either induced or repressed in
      human brain tumors are important in understanding the mechanism of tumor
      initiation and progression, stages of malignancy, in developing new approaches to
      the diagnosis and treatment of tumors. In this paper, differential hybridization
      of arrayed human fetal brain and postnatal brain and postnatal brain cDNA
      libraries revealed differences in the rate of hybridization signals with total
      cDNA probes of the human brain and glioblastoma multiforme for more than 150 cDNA
      clones. Sixteen nucleotide sequences with changed contents in tumors were
      identified by repeated differential hybridization of the cDNA clones selected by
      primary screening with the same total cDNA probes of the human brain and
      glioblastoma multiforme and by Northern-hybridization of RNA samples from the
      human and glial tumors. The results of an analysis of the increased expression of
      the gene encoding apolipoprotein E. DNA-binding protein B, mitochondrial (16S and
      12S) and cytoplasmic 28S rRNAs, Alu-containing transcripts, inactivation of
      cullin 1 gene and potential tumor suppressor gene TSC-22 are described.

PMID- 12214509
TI  - [The epidemiology of injuries to the spine and spinal cord in Saint Petersburg].
AB  - The epidemiology of injuries to the spine and spinal cord (ISSC) in Saint
      Petersburg and its dynamics in 1994 to 1996 were studied. The incidence of ISSC
      in the city was 0.44 cases per 10,000 (0.64@1000 for males; 0.28@1000 for
      females). During the period analyzed, there were increases in the incidence of
      ISSC by 1.8 times and in the frequency of admissions by almost 2 times. An
      epidemiological survey of ISSC made it possible to propose some measures to
      improve the organization of medical aid to ISSC patients in Saint Petersburg.

PMID- 12214510
TI  - [Perspective of skull reparative surgery using three-dimensional computed
      tomography and stereolithography].
AB  - The review presents the stages of the development and use of virtual three
      dimensional CT images. A possibility to get a 3D-based real skull model and an
      implant for reconstruction using a 3D-prototype technique (stereolithography) is
      a new step to the development of reconstructive surgery.

PMID- 12214511
TI  - [Perspectives of pharmacological correction of nitroxidergic vasorelaxation in
      subarachnoidal hemorrhage].
AB  - Subarachnoidal hemorrhage (SAH) causes cerebrovascular endothelial dysfunction
      that leads to impaired nitrosidergic vasorelaxation, delayed vasospasm, and
      cerebral ischemia. The purpose of the present review is to study the current
      potentialities of drug action on the system of generation of and the functional
      activity of nitric oxide (NO) in order to prevent and treat cerebral ischemic
      complications due to SAH. A scheme of the biosynthesis of NO and the mechanism of
      nitroxidergic vasorelaxation is presented. According to the direction of the
      action of a pharmacological agent (the biochemical target), the authors
      identified six groups of methods: 1) regulation of the level of a substrate; 2)
      activation of inhibition of NO-synthase enzymes; 3) action on the level of
      cofactors; 4) that on the metabolism of endogenous NO; 5) administration of
      exogenous NO; 6) action of the effector system of NO/cGMF. They show that not
      always an individual method is shown to be rather effective and safe for the
      treatment of patients after SAH. A concept of the combined use of methods from
      different groups for the synergism and potentiation of their impact on
      nitroxidergic vasorelaxation with a minimum of adverse effects is proposed.

PMID- 12214512
TI  - [Principles in the organization and surgical treatment of patients with non
      traumatic intracranial hemorrhage].
AB  - By taking into consideration the frequency of different forms of cerebral
      circulatory disorders, the authors determined the number of operations required
      to be performed for cerebral bleeding of various etiology in localities with
      different numbers of populations. The paper presents some results of treatment of
      patients with aneurysmal ruptures and hemorrhagic stroke at the Department of
      Neurosurgery, N. V. Sklifosovsky Research Institute of Emergency Care. The ways
      of improving the quality of care to patients with non-traumatic intracranial
      hemorrhage are outlined.

PMID- 12214513
TI  - [Opisthorchiasis morbidity in the town of Nizhnevartovsk].

PMID- 12214514
TI  - [Dot immunoassay with colloidal silver particles as a marker of specific antigen
      for testing human sera for brucellosis].
AB  - Whether the dot immunoassay is suitable for the detection of Brucella antibodies
      in human sera by using a colloidal silver-labeled Brucella specific antigen as a
      diagnostic tool is assessed. The antigen was the B. abortus 19BA protein
      polysaccharide complex isolated by Brucella acetic acid hydrolysis. The dot
      immunoassay is easy-to-use, cost-effective, highly sensitive, and therefore of
      more informative value in detecting Brucella antigens than routine serological
      tests (Huddleson test, Wright agglutination test, passive hemagglutination test,
      long-term complement fixation test, and Coombs test). It requires no use of
      expensive equipment and reagents.

PMID- 12214516
TI  - [Use of indirect micromodification of enzyme immune (IMEI) reaction for mass
      screening serological studies for Ixodes tick-borne borreliosis].

PMID- 12214515
TI  - [Efficiency and specificity of the KAT-test for rapid diagnosis of falciparum
      malaria].
AB  - A new rapid KAT Quick Malaria test for the diagnosis of falciparum malaria, which
      is based on the detection of a monoclonal antibody-antigen complex of malaria
      parasites, has been worked out by the KAT Medical CC in South Africa. The
      efficiency and specificity of the KAT test were compared with those of the
      microscopic method and with the ICT test for rapid diagnosis of P. falciparum and
      P. vivax. The polymerase chain reaction was used as a control test. Testing for
      malaria was performed on 98 blood samples from feverish patients in Vietnam and
      Tadjikistan and among the persons who had returned to Moscow from endemic
      regions. The efficiency of the KAT test for falciparum-malaria was found to be
      100% versus 90.5% with ICT. The absence of cross-reactions with P. vivax and the
      presence of pseudopositive results of the KAT test for fever cases of non-malaria
      origin indicate its high specificity. There was no correlation between the rate
      of test line colouring and the level of parasitemia. The KAT test yielded
      positive results only when gametocytes were found in blood specimens.

PMID- 12214517
TI  - [Progress in controlling ancylostomatoidea infections in Georgia].
AB  - Ancylostomatidae (Necator) infections are endemic in the west part of Georgia.
      This is promoted by natural and socioeconomic conditions of the region. The
      baseline Ancylostomatidae infection rates in the population average 43%. The
      specific features of an epidemic process of Ancylostomatidae infections under
      different regional conditions were clinically and epidemiologically studied,
      which made it possible to start implementing a whole package of differential
      therapeutical and preventive measures purposefully. This caused a drastic and
      steady-state reduction in invasion in the population. By 1990, a Ancylostomatidae
      infection rate of 0.009% was achieved, which was much lower than that of virtual
      Ancylostomatidae infection eradication.

PMID- 12214518
TI  - [Present-day specific features of visceral leishmaniasis in Georgia].

PMID- 12214519
TI  - [Role of sanitary and parasitological surveillance in sociohygienic monitoring].

PMID- 12214520
TI  - [Effect of tedin on clinical and allergic indices of viral hepatitis in the
      presence of giardiasis].
AB  - The efficacy of tedin was evaluated by comparing the outcomes of treatment in
      patients of two homogeneous groups. Group 1 comprised 30 patients with viral
      hepatitis B (VHB) concurrent with giardiasis who took tedin additionally to the
      basic therapy. Group 2 included 30 patients with the same conditions who received
      the basic therapy alone. The findings indicated that the supplement of tedin to
      the basic therapy in patients with VHB concurrent with giardiasis resulted in
      early regression of symptoms of allergy. In the above patient group, PCNT and
      PCZT were significantly less pronounced than those in the patients untreated with
      tedin.

PMID- 12214521
TI  - [A case of human anisakiasis in Kamchatka].
AB  - The clinical symptoms of intestinal anisakiasis, the location of the larvae of
      nematodes in the intestine, and changes of the organ at the site of helminthic
      attachment are described. The causative agent of this parasitic disease has been
      detected. This is Anisakis sp. L III.

PMID- 12214522
TI  - [Results of study of a combined focus of leptospirosis and hantavirus infection
      in the Primor'e territory].
AB  - Survey of the circulation and spread of causative agents of the infection among
      wild rodents may predict the activation of an epizootic process and the
      aggravation of an epidemic situation. The status of a combined focus of
      leptospirosis and hantavirus infection in the Primorye Territory was studied. It
      was found that mixed infection may run in pocket mice (Phascogalinae) under
      natural conditions.

PMID- 12214523
TI  - [Short-term prediction of a change in the total stock of Daursk suslik fleas in
      the Transbaikal natural focus of plague].
AB  - Based on 20-year studies of changes in the total store of the imago of Daursk
      souslik fleas in the Transbaikal natural focus of plague and on observations of
      variations in some environmental factors, equations of the short-term prediction
      of the size of fleas have been constructed for each month (from May to September
      inclusive). The equations include from one to three predictors that significantly
      influence the dynamics in the abundance of exoparasites. A nonlinear regression
      analysis was used for statistical data processing. The results and reliability of
      short-term stepwise prediction of the size of souslik fleas in the Transbaikal
      natural focus of plague from 1978 to 1987 are retrospectively considered.

PMID- 12214524
TI  - [Borrelia burgdorferi s.s. length and its variability].
AB  - The length of 469 Borreliae burgdorferi s.I. from the Ixodes ricinus and I.
      persulcatus images collected in the Moscow Region, that of 5433 B. burgdorferi
      s.s from the I. persulcatus nymphs and images cultured at a laboratory, and B.
      burdorferi s.s. grown on the BSK-II (1 and 10 passages) were measured. There was
      a wide range of variations in the length of specimens (3-74 microns) and in those
      of this group average sizes (10.7-24.8 microns). The lengths of Borelliae from
      natural and laboratory ticks after their molt were 17-18 microns. When the ticks
      were kept in the refrigerator as long as 1-2 years, the length of Borreliae
      decreased to 10.7-10.9 microns, upon multiple (10) passages on the BSK-II medium,
      their lengths increased to 24.8 microns (the differences being significant). When
      the length of Borreliae reduced due to their keeping in the refrigerator, their
      pathogenicity for albino mice diminished. This disappeared after multiple BSK-II
      medium passages. It is suggested that the length of Borreliae may serve as a
      marker of their pathogenicity.

PMID- 12214526
TI  - [The fundamentals of association of natural foci of zoonoses].
AB  - Reports on the role of hydrological conditions in the functioning of parasitic
      systems are analyzed. The authors point out that a range of issues including
      different aspects of combination phenomena is discussed there. They suggest that
      a concept of combination shall be replaced by a concept of association of
      parasitic systems and their relevant natural foci of zoonoses, which is of a
      larger scope. The fundamentals of the formation and functioning of associated
      parasitic systems and natural foci of zoonoses are discussed. These include the
      hydrological conditions of floodplain-river regions, the multiparasitic capacity
      of hosts and vectors, the multihost pattern of causative agents, and a diversity
      of mechanisms of their transmission. The transmission mechanism without which
      movement of causative agents and the existence of parasitic systems and foci are
      impossible is shown to be a global combining onset of parasitic systems. The
      hydrological conditions of floodplain-river regions act as the universal
      mechanism of transmission of pathogens. The dynamics of the mechanism determines
      the functioning of all other mechanisms of transmission.

PMID- 12214525
TI  - [Larvicidal activity of acrichine and dabechine injected into a hydatid cyst by
      electrophoresis: experimental study].

PMID- 12214527
TI  - [Tick-borne encephalitis morbidity in the Altai territory].

PMID- 12214528
TI  - [Use of western-immunoblotting to determine serum IgG-antibodies to antigens of
      different genotypes of Borrelia--Borrelia burgdorferi sensu stricto, Borrelia
      afzelii, and Borrelia garinii].
AB  - The reaction of the sera from 86 patients with Lyme borreliosis was evaluated in
      the immunoblotting using three genotypes of pathogenic Borrelia strains. The
      Russian isolates of Borrelia afzelii (strain IP3) and B. garinii 20047T (strain
      IP90) were compared with the USA typical strain B31--B. burgdorferi sensu
      stricto. The results were assessed by the criteria recommended for the USA and
      developed for B. burgdorferi sensu stricto. Certain differences were shown in the
      reactions of serum IgG with major proteins of three Borrelia genotypes. The sera
      interacted with p37 of an I-90 isolate and with p39 of both Russian isolates
      significantly more frequently. The rate of positive results of a serum test using
      the strain B31 was 18.6% (16 patients); 13 patients were additionally identified
      when the Russian isolates were applied. It is expedient to use the genotypes
      circulating in Russia as an antigenic material for immunoblotting. Criteria for
      positive serum test results may be individual for each genotype of Borreliae.

PMID- 12214529
TI  - [Outbreak of giardiasis at a preschool children establishment in the town of
      Perm'].
AB  - In November 2000, an outbreak of Giardiasis intestinalis with aqueous
      transmission was recorded in one of the microdistricts of Perm. Thirty six
      children aged 1-7 years fell ill, 2 parasitic carriers were identified among the
      staff. The diagnosis was parasitologically verified in all children with clinical
      manifestations. Enzyme immunoassay was positive in 87.5% of the patients with the
      parasitologically verified diagnosis. The aqueous nature of the outbreak was
      confirmed by the detection of Lamblia cysts in the samples of water from the
      transfer network of the microdistrict in November 2000 and by the higher
      incidence of giardiasis among the microdistrict's residents since April 2000.
      Macmiror in age-specific doses was used to treat patients. The therapeutical
      efficiency of one course was 100%. If outbreaks of intestinal infections of
      unknown etiology occur, a parasitological survey should be made among patients
      and those who have contacted with them. Prolonged diarrhea was one of the major
      symptoms of giardiasis during an outbreak of this intestinal infection.

PMID- 12214530
TI  - [False parasitic diseases].
AB  - The paper deals with the topical problem of false parasitic diseases (FPD) in
      patients with various organic (somatic and mental) disorders. A classification of
      groups of FPD patients is given according to their clinical and social signs.
      Examples of 6 cases of FPD observed by the authors and those published in the
      literature are presented. Simple and effective recommendations on the management
      of FPD patients are given.

PMID- 12214531
TI  - [Tick-borne borreliosis in the Iaroslavl region].
AB  - The present paper characterizes a natural focus of tick-borne borreliosis in the
      Yaroslavl Region, analyzes the incidence of this infection in the Region, and
      thus concludes that the density of the population living in the areas of the
      natural foci of tick-borne borreliosis has a significant impact on its epidemic
      process. The incidence of tick-borne borreliosis in the Yaroslavl Region has
      remained a challenge in the past 7 years. By the number of cases, this infection
      heads the list of naturally focal infections recorded in the Region. Examining
      long-term changes in the incidence and prevalence of tick-borne borreliosis in
      the Region revealed its high incidence in the population residing in the tidal
      marshlands and forest areas. At the same time the potential activity of natural
      foci of borreliosis due to the conditions that maintain the population of Ixodes
      ticks is high in the forest-field, southern, and meadow-forest-field regions.

PMID- 12214532
TI  - Old school values.

PMID- 12214533
TI  - Patient's angle.

PMID- 12214534
TI  - More than a meal.

PMID- 12214535
TI  - In good company.

PMID- 12214536
TI  - Student nurses' experiences of Project 2000.
AB  - AIM: The aim of the study was to investigate student nurses' experiences of
      Project 2000. METHOD: A sample of 76 students completed a questionnaire twice,
      once at the beginning of the course and again after one year. A second
      questionnaire comprising rating scales of how stressed they felt, was completed
      by a sample of 30 students weekly for the first year of the course. RESULTS:
      Seven areas of concern were identified: the theory component of the course,
      assessments, clinical practice, financial pressures, time management, personal
      development and personal difficulties. CONCLUSION: Sufficient data were generated
      to suggest that the experiences of Project 2000 students in other institutions
      are likely to be similar to those reported in the study. Recommendations for
      teachers, clinical staff and students are made.

PMID- 12214537
TI  - Inhaler devices: compliance with steroid therapy.
AB  - Many people with asthma do not take their medication as prescribed. The use of
      inhaler devices is an important factor in patient compliance with steroid
      therapy. Some of the features that influence compliance are discussed and the
      characteristics of inhaler devices are compared.

PMID- 12214538
TI  - Shock.
AB  - Shock is a life-threatening condition and to provide the best treatment, nursing
      care needs to focus on the cause of shock. Different types of shock and their
      causes are discussed to provide a better understanding of the nursing priorities
      involved.

PMID- 12214539
TI  - Lifelong point of contact.

PMID- 12214540
TI  - Quality assured.

PMID- 12214541
TI  - [Risk indicators of vitamin A deficiency in children younger than 15-years old
      from a slum area of Valencia, Venezuela].
AB  - Subclinical vitamin A (VA) deficiency is difficult to assess since there is not a
      single suitable indicator for every situation. With the objective of assessing VA
      status in a vulnerable group, 590 healthy children (< 15 years of age) from a low
      income community of Valencia, Venezuela, were studied. VA intake was assessed
      through 24 hour dietary recalls, risk of VA intake deficiency was assessed
      following the IVACG methodology, VA status was assessed through serum retinol
      levels (HPLCr) and Conjunctival Impression Cytology (CIC) according to ICEPO
      methodology. The sample was characterized by age (less than 7 years old, from 7
      to 10 years old, and 11 years old or older). Descriptive statistics and non
      parametric tests (Mann Whitney, X2) were performed. According to IVACG, 0.6% were
      at high risk of deficiency, 8.8% had moderate risk and 90.6% had low risk.
      Results from serum retinol showed 0.7% of deficiency (< 20 micrograms/dl), and
      25.1% of low levels (20-30 micrograms/dl); according to CIC, 11.1% of the sample
      was deficient. No relationship was found by age or sex. These prevalences
      identify the VA deficiency as a mild public health problem. Although there was no
      deficiency per se (< 10 micrograms/dl), this group has a higher vulnerability to
      infectious diseases since 25% of the sample showed low levels of serum retinol
      and 11.1% showed abnormalities in its epithelial cells.

PMID- 12214542
TI  - [Effects of secretory and osmotic diarrhea on rats intestinal function and
      morphology].
AB  - In order to compare intestinal morphology and function, diarrhea was produced in
      rats using laxatives in the diet. The 14 day study included two groups of rats
      with diarrhea (osmotic or secretory), two groups without diarrhea but with a
      degree of malnutrition which was similar to that seen in the rats with diarrhea
      (malnourished without diarrhea) and a well-nourished group (control). The
      inclusion of laxatives(lactose or bisoxatin acetate) cause a reduction in food
      intake, diarrhea an malnutrition. It also caused a reduction in dietary protein
      and fat digestibility which was proportional to the severity of diarrhea and more
      pronounced in secretory diarrhea. In the malnourished rats without diarrhea,
      malnutrition did not affect their absorptive function. Both in the rats with
      secretory and osmotic diarrhea an intestinal hypertrophy was observed. This
      hypertrophy was proportional to the severity of diarrhea and independent of its
      aetiology. In the intestines of the rats with both types of diarrhea there was
      inflammation, a greater number of mitotic figures but the flattening of the villi
      seen in the malnourished rats without diarrhea was not seen. In osmotic diarrhea
      there was, in addition, a patchy damage of the surface of the jejunal mucosa and
      an increment in the number of goblet cells, indicating a more severe intestinal
      deterioration. Since despite this greater deterioration, these rats absorbed more
      protein and fat we concluded that the alterations in intestinal morphology seen
      in this study was not predictive of intestinal function. The study also showed
      that diarrhea had a trophic effect on the intestine which did not occur in
      malnourished rats without diarrhea.

PMID- 12214543
TI  - [The nutritional status change the effectiveness of a dietary supplement of
      lactic bacteria on the emerging of respiratory tract diseases in children].
AB  - One hundred children 6 to 24 month old, normal or undernourished according to
      weight for height index, received during three months--autumn to winter--a
      dietary supplement of live Lactobacillus acidophilus and Lactobacillus Casei,
      10(7)-10(8)/ml in fermented milk (LB) or an equivalent amount of fluid milk (L)
      as control. Children's follow-up was performed as outpatients in the Hospital
      Posadas (Great Buenos Aires). Episodes of respiratory tract infections were
      recorded and classified according to severity as: Pneumonia (N); Bronchitis (B),
      Recurrent Obstructive Bronchitis (BOR) and upper respiratory tract infections
      (CVAS). 58% of children fitted the study protocol, 22 in the LB and 36 in the L
      group; 21 were undernourished and 37 presented normal weight/height. No deaths
      were recorded. Total episodes were 103: 34 in LB and 69 in L, that means a
      frequency of 1.55 and 1.92 episodes/children respectively. In LB a maximum of 3
      episodes/children was recorded, meanwhile the number reached 7 in L (p = 0.0373).
      Severity was higher in L than LB: 0.06 vs. 0 for N; 0.69 vs. 0.45 for B + BOR and
      1.17 vs. 1.09 for CVAS. In the control group frequency of severe pathologies was
      about twice in undernourished than in normal: 0.08 vs. 0.04 for N; 1.08 vs. 0.50
      for B + BOR; no difference was found for CVAS. Live lactobacillus supplement
      suppressed pneumonia and decreased bronchitis in undernourished as well as in
      normal. In this study undernutrition not only increased the chance of suffering
      severe acute respiratory tract infections but also impaired the effectiveness of
      the supplement to decrease severity. The effect is explained on the basis of the
      immunocompetence depression linked to an inadequate nutritional status.

PMID- 12214544
TI  - [Gene expression of Interleukin 1 in vitamin A and proteins deficiency].
AB  - The influence of low levels of protein and vitamin A on indicators of the immune
      response was assayed in rats. The levels of protein and vitamin A intake of the
      Cuban population affected by epidemic neuropathy in 1993 was reproduced in 4
      diets: control, protein deficiency (DP), vitamin A deficiency (DA), protein and
      vitamin A deficiency (DAP). The Peyer's patches evaluated the Interleukin 1
      expression gene and was related with corporal weight, food intake, serum protein,
      vitamin A, immunology indicators and histology evaluation (spleen, thymus and
      liver). Protein deficiency generated a significant decrease of the expression
      gene of Interleukin 1. Atrophy signs in lymphoid tissues and morphologic changes
      in the liver were associated with the dietary protein utilization. Protein and
      vitamin A deficiency generated significant stimulation of the Interleukin 1
      expression gene with increase of the level of the inflammatory state indicators
      as serum alpha protein, total complement and neutrophils. This stimulation could
      be generated by a deficient retinol mobilization to tissues. These results
      support the hypothesis of the function of cytokines as mediators of subclinical
      symptoms of the immune system during the nutritional affectations.

PMID- 12214545
TI  - [Estimation of potentially available protein in infant starting formulas for term
      and preterm neonates].
AB  - Sixteen milk-based starting formulas were analyzed with the aim of calculating
      their "true protein" content and assessing "in vitro" protein digestibility, in
      order to estimate levels of potentially available protein. Ten of them were
      designed for term infants: 7 had a casein:whey protein ratio 40:60 (adapted
      formulas) and 3 a ratio 80:20 (non-adapted); the 6 remaining formulas (all
      adapted) were for preterm infants. Nitrogen was determined by the Kjeldahl
      method. True protein was calculated as (total N--non-protein N) x 6.25. NPN was
      determined in the soluble fraction, after protein precipitation with 24%
      trichloroacetic acid and centrifugation. Digestibility was assessed by digestion
      with pepsin and pancreatin, and defined as the increase in non-protein N after
      enzymatic digestion. Values for true protein were from 1.3 to 2.3 g/dL and for
      non protein N, from 4.5 to 13.7%. Digestibility values varied between 59.0 and
      92.5%; an inverse trend was observed between protein digestibility and protein
      content. Considering both the "true protein" levels and their digested
      proportions, all preterm and 60% of the term formulas would present potentially
      available amounts below those recommended. These observations constitute an
      alert, even though this method of assessing "in vitro" protein digestibility
      represents only an approximation to physiological processes; however, it could be
      useful in order to evaluate the intensity of the heat treatments to which these
      formulas were subjected. On the other hand, since NPN allows the estimation of
      the true protein provided by the formulas, either its percentage or the true
      protein content could be included on the label.

PMID- 12214546
TI  - [Determination vitamin A source foods by pregnant women, using a simplified
      dietary assessment (SDA)].
AB  - The International Vitamin A Consultative Group (IVACG) developed a research
      instrument based on consumption of vitamin-A food sources to classify populations
      into groups of high, moderate and low deficiency risk in the consumption of this
      nutrient. The instrument was tested on a population of 91 pregnant women who
      attended prenatal health care service run by School of Public Health of the
      University of Sao Paulo. Such instrument was termed Simplified Dietary Assessment
      (SDA) and it is comprised of a 24-hour dietary recall--Consumption Index (CI) and
      consumption frequency questionnaire--Usual Food Pattern (UFP). SDA pointed out
      the most consumed daily and weekly foods as being milk in liquid form, tomato,
      lettuce, margarine and banana. All these food sources belong to groups of low and
      moderate vitamin A content. Assignment in risk groups was based on the
      recommended dietary intake proposed by the Food and Agriculture Organization of
      the United Nations--(FAO/OMS--1991) and two-thirds of the recommended intake was
      considered the cutting off point. According to data obtained by the SDA, more
      than 50% of the population interviewed was assigned to the High and Moderate risk
      groups for deficiency in vitamin A intake. Statistical analysis of the data
      revealed a significant statistical correlation r = 0.50 (p > 0.005) and a
      weighted Kappa value of (kw = 0.207), which suggests that the SDA is a useful
      instrument and is a reasonable means for risk assignment of vitamin A deficiency
      among groups with inadequate levels of intake of foods as sources of this
      nutrient. However, the results suggest that in order to evaluate vitamin A intake
      appropriately, a larger number of applications of the IC questionnaires would be
      required.

PMID- 12214547
TI  - Prevalence of anemia during pregnancy: results of Valencia (Venezuela) anemia
      during pregnancy study.
AB  - To determine the prevalence of anemia during pregnancy in Venezuelan pregnant
      women. By using a cross-sectional study, 630 Venezuelan pregnant women in their
      third trimester at labor from the Valencia Anemia during Pregnancy Study were
      studied. Anemia during pregnancy was defined according to WHO guidelines (Hb < 11
      g/dl), iron deficiency was considered when serum ferritin level was < 12 ng/ml,
      and when serum folate level was < 3 ng/ml, it was considered as folate
      deficiency. 630 pregnant women (mean [+/- SD] age, 24 +/- 6.4 years) having an
      average of Hb 11.38 +/- 1.47 g/dl [95%CI = 11.27 to 11.50] were studied. No
      patient had hemolytic anemia nor clinical infections. Almost all patients were
      from low or very low socioeconomic status. Prevalence of anemia was 34.44%
      (severe: 1.8%, moderate: 15.2%, and mild: 83%). Iron deficiency anemia (IDA) was
      present in 39.2% (95%CI = 32.7 to 45.7), prevalence of folate deficiency anemia
      (FDA) was 11.98% (95%CI = 7.6% to 16.3%). Combined anemia (IDA and FDA) occurred
      in 11.52% (95%CI = 7.27% to 15.7%). Multivariate analysis showed that multiparous
      (odds ratio -OR-: 1.95, 95%CI = 1.28 to 2.97, p = .002) and supplement use of
      iron (OR: .55 (95%CI = .33 to .91, p = .02) are associated with IDA. The factors
      associated with FDA were: supplement use of folic acid (OR: .37 (95%CI = .19 to
      .71, p = .003) and appropriate prenatal control (OR: .51 95%CI = .27 to .96, p =
      .04). Prevalence of anemia during pregnancy was found to be high. Educational
      efforts should be stressed in order to encourage improvements in the prenatal
      care visits.

PMID- 12214548
TI  - [Feeding practices among rural families of Medellin, Colombia].
AB  - Some feeding practices among families of Medellin's Districts: Santa Helena,
      Belen Altavista, Palmitas, San Cristobal and San Antonio de Prado are presented.
      It is a descriptive and transversal investigation. The sample used was
      representative and probabilistic. Breast feeding practice is prevalent in all the
      Districts mentioned above; a duration average of the breast feeding was observed
      between 10 and 13 months (p < 0.05), 29% of the women, declared having some kind
      of difficulty trying to breast feed their last child. The main reasons for this
      were: low milk production and illness of the mother. 53% of the mothers informed
      to have introduced the complementary feeding before four months. Fruits and
      vegetable consumption was low, comparing it with the high level of consumption of
      beans. The cooking methods most used were deep frying and boiling. The oils and
      lard used have a high content of saturated fat acids. Most of the members of the
      families, they consume the main foods and they make it in the home (breakfast,
      lunch and supper). On the other hand in between meals tend to disappear,
      especially midmorning and late snack.

PMID- 12214549
TI  - [Consumption of fruits in an adult population from Costa Rica].
AB  - The consumption of fruits and it relation with the health and socioeconomic
      condition of an adult Costa Rican population is described. The study included a
      cross sectional and descriptive analysis in men and women 18 years old or older.
      Ten-house blocks were selected by affinity in a community or neighborhood in
      Cartago. Data were collected in a survey using home direct structured interviews
      carried out in the afternoons or during the weekend in February, 2000. Eighty
      percent of the 161 people interviewed were women. Results showed that the higher
      consumption of fruits was described in women who were older that 60 years old
      and, who proceed from a medium-high economic stratum or have a high schooling
      condition (2.3 +/- 1.0, 2.50 +/- 1.3 y 2.0 +/- 1.3 portions, respectively). No
      statistical significant difference was found in any of the variables evaluated.
      Data also showed that, in contrast with what it was expected, people that
      considered their health condition as bad, suffered chronic diseases, practiced
      physical exercise, took vitamin supplement or smoke, showed a higher consumption
      of fruits that those who do not have those conditions. The difference, however,
      showed to be no significant and the consumption of fruit showed to be not
      adequate in both groups. In conclusion, the amount and frequency of fruit
      consumption were inadequate in the population studied. The necessity of
      developing nutritional education strategies to promote a gradual increment in the
      consumption of fruits to approach the recommendation of the National Alimentary
      Guidelines is recommended.

PMID- 12214550
TI  - [Isolation of Gram-positive bacteria from raw milk with antimicrobial residues].
AB  - Two hundred samples of raw milk were collected at the receiving plants located in
      three areas of high milk production in Zulia state, Venezuela. The CTT test and
      trial disk were used in order to detect the presence of antimicrobials. The
      positive samples were inoculated in tripticase soy broth, human blood agar and
      manitol salt agar in order to isolate Gram-positive bacteria. The identification
      of species was performed through biochemical tests. It was found that 45 samples
      (22.5%) of analyzed milk contained antimicrobials, and bacterial growth was
      obtained in 35 of them. 100 strains were isolated namely: 44 Staphylococcus, 19
      Streptococcus, 17 Enterococcus, 9 Bacillus, 4 Micrococcus, 4 Corynebacterium and
      3 Lactococcus. The most frequently isolated specie was S. aureus, the main
      producing agent of bovine mastitis in Zulia state, a microorganism frequently
      associated in the country to food-borne intoxications, associated to cheese
      processed from raw milk. It is recommended to apply control programs for the use
      of antibiotics.

PMID- 12214551
TI  - [In vitro germicide action of disinfectant products used in the food industry].
AB  - There is a wide offer of disinfectant products, for the food industry, available
      in the market, such as chlorine, iodine and quaternary ammonium compounds and
      their respective derivatives. However, new alternative products have emerged, for
      instance grapefruit seed extract, and peracetic and lactic acids. The present
      study was carried out in order to analyze in vitro the germicide effect, from the
      grapefruit seed extract (400 ppm), peracetic acid (2000 ppm) and lactic acid
      (20,000 ppm) at the manufacturer recommended action time, and other additional
      times. The germicide effect was tested against microorganisms such as Escherichia
      coli, Staphylococcus aureus, Streptococcus faecalis and Pseudomonas aeruginosa.
      In each case, the death kinetic was determined through the evaluation of the
      germicide effect (%), specific death rate (t-1) and the decimal reduction time
      (min). From the evaluated products, the best germicidal effect at the
      manufacturer conditions was reached by peracetic acid (2000 ppm) at 1 min, which
      presented the lower decimal reduction times compared with the other tested
      microorganisms. Generally speaking, Gram positive microorganisms showed a greater
      sensibility to the disinfectant action.

PMID- 12214552
TI  - [Characterization of peptide and amino acid profile in casein hydrolysates].
AB  - The nutritional quality of protein hydrolysates has been related in several
      reports to their di- and tripeptide contents. In the present work different
      hydrolytic conditions were tested using papain in order to prepare casein
      hydrolysates with a suitable peptide profile for being used in special diets. The
      hydrolysates were fractionated by size-exclusion HPLC and the rapid Correct
      Fraction Area method was used for quantifying the peptides. Among the five
      hydrolytic conditions studied, three of them gave rise to preparations having
      nutritionally similar peptide profiles. However, the use of the temperature of 37
      degrees C and enzyme:substrate ratio (E:S) of 2% may probably be the most
      economical condition for industrial production.

PMID- 12214553
TI  - [Edible coating effects on the sensory quality of green bell pepper fruits
      (Capsicum annuum L.) during storage].
AB  - Edible coating based on carboxymethyl cellulose (CMC) and stearic acid were
      applied on green bell peppers (Capsicum annuum L.) samples in order to
      investigate its effects as protecting agent to enhance natural characteristics of
      products. Samples were submitted to three lots according to: (T1) uncoated; (T2)
      coated in lower part of the stem; (T3) coated all over the surface (T3). During
      storage at 5 +/- 1 degrees C, for 28 days, sensory quality and weight loss were
      evaluated. Sensory characteristics such as color, appearance and firmness were
      controlled using a composite scoring test. At the end of the study, T3 treatment
      showed better sensory stability than T1 (p < 0.05), none significant changes
      between T2 and T3 were found. The coated samples showed less firmness
      deterioration compared with control samples. The color was the attribute that
      changed less, without significant difference between treatments (p > 0.05).

PMID- 12214554
TI  - [Optimization of a spaghetti formula enriched with dietary fiber and
      micronutrients for elderly people].
AB  - Several studies have demonstrated low dietary fiber intake in elderly people,
      which increases the risk of diseases such as constipation, colon cancer and
      diverticulosis. A spaghetti formula enriched with lupin fibre was developed to
      increase the dietary fibre intake in elderly people, as spaghetti are frequently
      consumed in this age group. Sweet lupin bran (Vitafiber) was used as fibre source
      and gluten was used as improving additive. Response surface methodology with a
      two variable composite rotatable design was applied to optimize the formulations.
      The independent variables were lupin bran (7.14-14.29%) and gluten Vital (0.1
      2.0%). The dependent variables were the responses of a trained 10-member sensory
      panel who evaluated the sensory quality parameters color, shape, aroma, flavor
      and texture by the Karlsruhe 9-point test. The optimized formula was prepared
      with 66.7% semoline, 7.14% lupin bran, 1.05% gluten and 24.7% water, enriched
      with 0.019% of a vitamin premix (A. E, D, B2, B12 and folic acid) and with 0.41%
      of a mineral premix (Ca, Fe, Zn), in order to meet 30% of the RDA for the elderly
      per 100 g dry spaghetti. The dietary fibre content of the optimized product was
      11.05 g/100 g. The study showed that fibre-enriched spaghetti formula is a good
      way to increase dietary fibre intake in elderly people, as it is a common food,
      simple to prepare and easy to eat.

PMID- 12214555
TI  - Synthesis of a rabbit polyclonal antibody to the human sodium-dependent
      multivitamin transporter.
AB  - In mammalian cells, biotin is covalently attached to carboxylases and histones
      and is required for cell proliferation and function. Cellular uptake of biotin
      (as well as pantothenic acid and lipoic acid) is mediated by the sodium-dependent
      multivitamin transporter, SMVT. Studies of cellular biotin homeostasis have been
      hampered by the lack of an antibody to SMVT. Here, we describe the synthesis of a
      rabbit polyclonal antibody to human SMVT. Using this antibody, SMVT has been
      identified in human peripheral blood mononuclear cells, Caco-2 cells, and HepG2
      cells. Moreover, we observed that cells respond to proliferation with increased
      synthesis of SMVT.

PMID- 12214556
TI  - Effect of citric pectin on beta-carotene bioavailability in rats.
AB  - The effect of citric pectin on the bioavailability of synthetic beta-carotene was
      studied. Thirty Wistar rats were used, ten animals were sacrificed at the
      beginning of the experiment and remaining animals were divided into two groups
      and received the following diets for 30 days: control group (CG)--24 micrograms
      beta-carotene/g diet + 0% citric pectin; experimental group (EG)--24 micrograms
      beta-carotene/g diet + 7% citric pectin. Plasma and liver beta-carotene, vitamin
      A, and retinyl palmitate concentrations were determined by high-performance
      liquid chromatography (HPLC). Plasma retinol concentration was 1.42 +/- 0.36
      mumol/L for CG and 1.10 +/- 0.24 mumol/L for EG (p = 0.1), and plasma beta
      carotene concentration was 0.20 +/- 2.51 mumol/L for CG and 0.07 +/- 0.04 mumol/L
      for EG (p = 0.01). Only traces of retinyl palmitate were detected in CG and none
      in EG. Retinol did not differ significantly between groups CG and EG, while a
      significantly higher beta-carotene concentration was observed for CG. Liver
      concentrations of retinol (CG: 4.90 +/- 2.51 micrograms/g; EG: 2.68 +/- 1.12
      micrograms/g), beta-carotene (CG: 0.98 +/- 0.28 microgram/g; EG: 0.11 +/- 0.06
      microgram/g), and retinyl palmitate (CG: 95.47 +/- 45.13 micrograms/g, EG: 37.01
      +/- 17.20 micrograms/g) differed significantly between groups (p < 0.05), with a
      lower concentration being observed for EG. We conclude that 7% citric pectin in
      the rat diet decreases the bioavailability of synthetic beta-carotene, reducing
      the liver reserves of vitamin A and beta-carotene.

PMID- 12214557
TI  - Additive action of vitamins C and E against hydrocortisone-induced genotoxicity
      in human lymphocyte chromosomes.
AB  - In earlier reports, hydrocortisone administration to human lymphocytes in culture
      was shown to cause chromosomal aberrations and increased sister chromatid
      exchanges. With a view to study the ameliorative action of some antioxidants
      against this effect, vitamins C and E were used separately and in combination
      along with hydrocortisone treatment, at different dosage and for different
      durations, on human lymphocyte cultures. The levels of chromosomal aberrations
      and sister chromatid exchanges were lowered, suggesting a protective role of
      vitamins against genotoxic damage. Administration of vitamins C and E combined
      appeared to be more effective in preventing chromosomal damage than separate
      administration, demonstrating the additive action of these vitamins against
      steroid-induced genotoxicity.

PMID- 12214558
TI  - Vitamin A metabolism is altered in brown Norway and long-Evans rats infused with
      naftidrofuryl or erythromycin intravenously.
AB  - Enzymatic retinyl ester hydrolysis is a key reaction for maintaining cellular
      retinol homeostasis. The ability of naftidrofuryl and erythromycin to inhibit
      retinol liberation by retinyl ester hydrolase (REH) in vitro suggests an ability
      to interfere with vitamin A metabolism in vivo, particularly during hepatic
      processing. To address this question, systemic and local response to these agents
      were studied in Brown Norway (BN) and Long-Evans (LE) rats. The study was
      conducted in two parts: a drug-loading phase and a washout phase. Analysis of
      variance of the time course changes in plasma retinol during the post-treatment
      period (Days 10-18) showed rat strain (p < 0.04) and time (p < 0.001; strain-by
      time interactive effect, p < 0.001) to be significant factors, but drug exposure
      (p = 0.19) was not significant. Endpoints included hepatic REH activity, size and
      composition of the liver vitamin A stores, and retinoid content of the kidneys.
      Rats recovering from naftidrofuryl dosing demonstrated a lower REH activity than
      did animals recovering from erythromycin treatment (p < 0.009). The major side
      effect of erythromycin is vitamin A accumulation in the liver (p < 0.001) and
      reductions in retinol reserves (p < 0.02) were among the consequences of
      naftidrofuryl treatment. In the kidney of LE rats, there were higher
      concentrations of vitamin A (p < 0.003) secondary to naftidrofuryl exposure.
      Together our data suggest that clinically achievable concentrations of the drugs,
      given as a continuous infusion, produce aberrations in vitamin A metabolism.

PMID- 12214559
TI  - Serum retinol of Chadian nomadic pastoralist women in relation to their
      livestocks' milk retinol and beta-carotene content.
AB  - Human serum retinol and livestock milk retinol levels were assessed as part of a
      study on the health status of Chadian nomadic pastoralists and their livestock in
      close partnership between Chadian public health and livestock institutions. Of
      the examined women (n = 99), 43% were moderately retinol-deficient (0.35 mol/L <
      x < 0.7 mol/L 95% CI; 33-54%), and 17% severely retinol-deficient (< 0.35 mol/L
      95% CI; 10-26%). None of the interviewed women (n = 87) reported the consumption
      of fruit, and only two of fresh vegetables were reported consumed in the past 24
      hours. Milk is the almost exclusive source of vitamin A for these populations.
      Goats (n = 6) had the highest average milk retinol level (329 +/- 84
      micrograms/kg [mean +/- SEM]), followed by cattle (n = 25; 247 +/- 32
      micrograms/kg), and camels (n = 12; 120 +/- 18 micrograms/kg). Milk retinol
      levels did not differ between the rainy and dry seasons. Human serum retinol
      depends significantly on livestock milk retinol levels (partial slope 0.23; 95%
      CI: 0.008-0.47). Our study supports the use of goat and cow milk as an important
      source of vitamin A in pastoral nomadic settings. However, the levels still
      require to be complemented further by promoting green leafy vegetables, fruits,
      and supplements.

PMID- 12214560
TI  - Effects of subcutaneously injected graded doses of all-trans retinoic acid and
      all-trans retinoyl beta-glucuronide on the outcome of pregnancy in Sprague-Dawley
      rats.
AB  - The effects of single subcutaneous injections (s.c.) of graded doses (20, 40, 80,
      160, 320, and 480 mumol/kg body weight (BW) of all-trans retinoic acid (RA) and
      all-trans retinoyl beta-glucuronide (RAG) on day 8.5 of gestation on the outcome
      of pregnancy in Sprague-Dawley rats was studied. At dose levels of 20, 40, and 80
      mumol/kg BW, neither RA nor RAG showed any adverse maternal or fetal effects.
      However, at dose levels of 160, 320, and 480 mumol/kg, RA was found to be much
      more toxic than RAG to both mother and fetus. Fetuses of animals receiving a 160
      mumol/kg BW dose of RA were significantly reduced in weight and length, while
      animals receiving the same dose of RAG had fetuses of normal size. RA doses of
      320 and 480 mumol/kg BW resulted in symptoms of maternal toxicity and even death.
      In contrast, RAG at these high levels produced no signs of maternal toxicity. RAG
      doses of 320 and 480 mumol/kg BW were also less toxic to fetuses. RA doses of 320
      mumol/kg BW resulted in only 8% live births, while animals treated with an
      equivalent amount of RAG experienced 95% live births. Animals receiving a dose of
      480 mumol/kg BW of RA had no live births, but similar doses of RAG resulted in
      28% live births and pups of normal size.

PMID- 12214561
TI  - Serum antioxidants and subsequent mortality rates of all causes or cancer among
      rural Japanese inhabitants.
AB  - The purpose of this study was to investigate whether a relationship exists
      between mortality rates and serum antioxidant levels among Japanese inhabitants.
      The follow-up subjects, who participated in comprehensive health examinations,
      consisted of 2444 inhabitants (949 males and 1495 females) of a rural area in
      Hokkaido, Japan. Between 1991 and December 2000, 146 subjects (94 males and 52
      females) died, with cancer accounting for 76 of these deaths (48 males and 28
      females). Serum samples at fasting were collected at entry into the study, and
      serum levels of beta- and alpha-carotenes, lycopene, beta-cryptoxanthin,
      canthaxanthin, zeaxanthin/lutein, tocopherols, and retinol were measured
      separately by high-performance liquid chromatography (HPLC). The statistical
      analyses were conducted using the Cox proportional hazard model. Age- and gender
      adjusted hazard ratios of the groups with high serum levels of lycopene, beta
      carotene, zeaxanthin/lutein, and total carotenoids compared to those with low
      serum levels were 0.36 (95% C.I: 0.19-0.69), 0.53 (0.29-0.95), 0.73 (0.43-1.25),
      and 0.52 (0.30-0.92) for cancers of all sites, and 0.44 (95% C.I: 0.28-0.69),
      0.59 (0.39-0.90), 0.61 (0.40-0.93), and 0.50 (0.33-0.76) for all causes,
      respectively. Similar results were found after adjusting for gender, age, smoking
      habits, alcohol consumption, and serum levels of total cholesterol and glutamic
      pyruvic transaminase (GPT) activity. Moreover, after excluding mortality within
      the first three years of follow-up, the hazard ratios of subjects with high serum
      levels of lycopene, total carotenes, and total carotenoids were significantly and
      inversely associated with subsequent mortality from all causes and cancers of all
      sites after adjusting for gender, age, and serum levels of total cholesterol,
      alpha-tocopherol, and retinol. These results suggest that high serum levels of
      antioxidants, such as lycopene, beta-carotene and zeaxanthin/lutein, play roles
      in preventing death from cancer and from all causes. However, high serum levels
      of tocopherols and retinol did not demonstrate clear associations with either low
      mortality rates from all causes or cancer of all sites.

PMID- 12214562
TI  - Differences in the accumulation of ascorbic acid in normal, myeloperoxidase
      deficient and NADPH-oxidase deficient granulocytes.
AB  - Granulocytes contain large quantities of ascorbic acid (AA). The uptake mechanism
      is mainly restricted to the accumulation of the oxidized form, dehydroascorbate
      (DHA). We investigated the uptake of ascorbic acid and dehydroascorbate of
      normal, myeloperoxidase (MPO)-deficient, and NADPH-oxidase-deficient
      granulocytes. The accumulation of ascorbic acid was increased in all types of
      granulocytes after stimulation with phorbol-myristate-acetate, whereas the NADPH
      oxidase-deficient cells showed a decreased uptake compared to normal and MPO
      deficient cells. The intracellular concentration of ascorbic acid was further
      enhanced after incubation of granulocytes with DHA, most prominently in NADPH
      oxidase-deficient granulocytes. MPO-deficient granulocytes are not able to
      produce HOCl after activation. The granulocytes of one individual with total MPO
      deficiency accumulated ascorbate in higher concentrations than did cells with
      partial MPO deficiency, indicating that HOCl is of minor importance for the
      oxidation of ascorbate. Since the ability of MPO-deficient cells to kill
      microorganisms is pronounced in contrast to NADPH-oxidase-deficient cells,
      effective mechanisms of compensating for the absence of HOCl must exist. We
      hypothesize that the enhanced uptake of ascorbic acid combined with an enhanced
      superoxide anion production may favor the generation of OH radicals via the
      Fenton reaction.

PMID- 12214563
TI  - Experience with ferrous bis-glycine chelate as an iron fortificant in milk.
AB  - The objective of this study was to test whether milk is an appropriate vehicle
      for fortification with ferrous bis-glycine chelate and whether it has any effect
      on milk's organoleptic properties. In addition, the study examined the children's
      acceptability and tolerance of the fortifying agent. One hundred thirty-one
      children aged 6-14 years (79 males and 52 females) from two dormitories of the
      Ministry of Social Welfare in Riyadh City, Saudi Arabia participated in this
      study. The results of this trial showed that milk fortified with this iron
      chelate has unaltered organoleptic properties and is well accepted by the
      children. Hemoglobin and serum ferritin levels were measured before and after
      consuming one liter of milk fortified with 30 mg ferrous bis-glycine chelate per
      liter (6 mg elemental iron per liter) per day, for a period of three months. The
      prevalence of anemia (Hb < 12 g/dL) significantly dropped from 25.3 to 5.0%, and
      23.0 to 9.6%, among boys and girls respectively. The prevalence of low serum
      ferritin values among boys dropped from 8.8 to 5.9% and significantly from 21.1
      to 12.1% among girls. No control group was included in this study. It is
      concluded that ferrous bis-glycine chelate in milk does not alter milk's
      organoleptic properties; furthermore, it improved hemoglobin and ferritin serum
      levels among anemic children, suggesting milk as an appropriate vehicle for
      fortification with this chelate.

PMID- 12214564
TI  - Calcium intake in relation to diet and health indicators in Cretan primary and
      high school pupils, Greece.
AB  - In recent years, the issue of dietary calcium (Ca) requirements is said to have
      caused more controversy than requirements for any other nutrient. There is little
      published data on dietary Ca intake levels in Greek children and relationships
      with other health indicators. Pupils at twenty primary and ten high schools in
      Crete, Greece, were examined as part of a wider study of the dietary habits and
      health status of children and adolescents. A total of 1054 children participated:
      583 9- to 12-year-olds and 471 14- to 16-year-olds. "High" and "low" Ca intake in
      each age group was defined using upper and lower Ca intake quartiles for each
      sex. Multiple regression techniques were used to examine associations after
      adjustment for energy intake. No statistical association was observed between
      calcium intake and serum lipoproteins, anthropometric measurements, or physical
      activity status. Energy-adjusted Ca intakes were positively associated with
      intakes of protein, saturated fatty acid (SFA), magnesium, phosphorus, vitamin A,
      and vitamin B2, whereas higher Ca intakes were associated with lower
      monounsaturated fatty acid (MUFA) and omega-6 fatty acid intakes. In both age
      groups, pupils with high Ca intake had higher intakes of the food groups "milk
      and milk products" and "grains and grain products" than those with low Ca intake,
      although even "high" Ca intake in older female Cretan pupils (with a 75th
      percentile cut-off of 999 mg/day) may not be at adequate levels.

PMID- 12214566
TI  - Special issue: Selenium and cancer: Larry C. Clark memorial issue.

PMID- 12214565
TI  - Biotin-dependent carboxylase activities in different CNS and skin-derived cells,
      and their sensitivity to biotin-depletion.
AB  - The validity of various transformed and untransformed CNS and skin-derived cell
      cultures as a model for studying effects of biotin deficiency was tested. In
      biotin-sufficient conditions (0.1-10 mumol/L) all cell types showed considerable
      activities of the four biotin-dependent carboxylases. Notably, pyruvate
      carboxylase activity was also present in the different neuronal cells. One
      passage in low-biotin medium (6-130 pmol/L) lowered mitochondrial carboxylase
      activities in all cell types, but to varying degrees. Sensitivity to biotin
      depletion was greatest in three neuronal cell types, Roc-1 oligodendroglia, and
      three keratinocyte cell types (carboxylase activities decreased to 2-11% of
      maximal); intermediate in primary astrocytes and C6 glioma (decreased to 12-28%),
      and least in SAOS2 sarcoma and skin fibroblasts (decreased to 32-85%).
      Transformed and untransformed cell lines of the same cell type showed similar
      sensitivity. We conclude that cultures of different transformed CNS and
      keratinocyte cell types allow the study of effects of biotin deprivation.
      Carboxylase activities of neurons, oligodendroglia, and keratinocytes were much
      more sensitive to biotin depletion than fibroblasts. This may be an important
      factor in the pathogenesis of neurological and cutaneous abnormalities in
      congenital biotinidase deficiency where recycling of biotin is deficient.

PMID- 12214567
TI  - Larry Hollingsworth Strasburger, MD: Twenty-seventh president of the American
      Academy of Psychiatry and the Law.

PMID- 12214568
TI  - [Proceedings and abstracts of the 8th and 9th Annual Meeting of the Society for
      Rehabilitation in Digestive and Metabolic Diseases, Kreischa 2000 and Bad Driburg
      2001].

PMID- 12214569
TI  - Spot the diagnosis. Primary cutis verticis gyrata.

PMID- 12214570
TI  - Fractures during physical therapy.

PMID- 12214571
TI  - Metaphyseal fractures.

PMID- 12214572
TI  - Vital signs monitors.

PMID- 12214573
TI  - Early adoption of HIV-1 resistance testing in the San Diego County Ryan White
      CARE Act Program: predictors and outcome.
AB  - This research identifies predictors and outcomes of early use of human
      immunodeficiency virus type 1 (HIV-1) resistance testing in the San Diego County
      Ryan White CARE Act program. Between January and November 2000, 98 patients
      receiving care in 7 clinics participated in the resistance testing program.
      Provider characteristics predictive of participation included number of patients
      and percent of practice devoted to HIV care and number of HIV-related continuing
      medical education hours over the preceding 12 months. Providers rarely requested
      expert panel review of test results, and expert review was not predictive of
      better viral load responses. Regimens specified before knowledge of resistance
      results had more active drugs than those prescribed after knowledge of test
      results. Phenotypic susceptibility was predictive of virologic response, as was
      degree of prior nucleoside analogue exposure. There was little relationship
      between phenotypic susceptibility and a clinician's decision to prescribe a drug.
      Early adopters of this technology were more experienced HIV providers than their
      colleagues and utilized susceptibility information using reasoning processes in
      which resistance was a contributory but not necessarily dominating factor.

PMID- 12214574
TI  - CDC Discourages STD treatment.

PMID- 12214575
TI  - Test kit shortage.

PMID- 12214576
TI  - Abstracts of the 8th Conference of the Federation of Infection Societies, 2001.

PMID- 12214577
TI  - Cyclosporin A pharmacokinetics in a patient with psoriasis and obesity,
      presenting with high levels of low-density [correction for destiny] lipoprotein.

PMID- 12214578
TI  - Clinical-pharmacokinetic aspects of prolonged effect duration as illustrated by
      beta2-agonists.
AB  - Regularity is a key element of maintenance drug treatment; compliance is crucial
      for treatment success. Once- or twice-daily intake of a drug is always easier to
      comply with than regimens requiring more frequent dosing. Bronchodilating
      treatment was used as an example to illustrate how sustained duration of effect
      can be achieved by two different approaches: oral administration of the
      terbutaline prodrug bambuterol and inhalation of formoterol. Bioanalytical
      methods were employed to monitor the kinetic fate of bambuterol and formoterol in
      plasma, urine, or faeces. Generated terbutaline in plasma was used as a marker of
      effect for bambuterol. Established clinical laboratory tests were used to assess
      local and systemic effects of inhaled formoterol compared with salbutamol.
      Recommended doses of bambuterol, 10-20 mg once daily in adults, normally produced
      plasma concentrations of the active moiety terbutaline within therapeutically
      relevant limits. Dose proportionality for terbutaline makes dosing with
      bambuterol predictable. Compared with adults, children should be given higher
      doses than indicated by their lower body weight. Pharmacokinetic analysis
      indicated that absorption of bambuterol was slow and multi-phasic and that slow
      biotransformation to terbutaline occurred both presystemically and systemically.
      Systemically circulating formoterol was rapidly eliminated, the inactive (S;S)
      formoterol more rapidly than the active (R;R)-formoterol. An inactive phenol
      glucuronide was the main metabolite, and a previously unknown sulphate metabolite
      was discovered. Duration of systemically mediated cardiovascular or metabolic
      side-effects of inhaled formoterol seemed not to differ from those of an inhaled
      systemically equieffective dose of salbutamol. There was a trend suggesting that
      the magnitude of systemic side-effects may be less pronounced after inhalation of
      formoterol compared with a locally equieffective dose of inhaled salbutamol. Both
      approaches to sustaining stimulation of beta2-adrenoceptors have their pros and
      cons. Bambuterol can be dosed orally once daily, but full effect is reached
      slowly. The effect of formoterol is reached within a few minutes, but
      administration must occur via the lungs, often twice daily. Both treatments,
      however, give 24-h symptom relief during regular treatment.

PMID- 12214581
TI  - Proceedings of the International Health Evaluation Association meeting, IHEA 2000
      in Taipei, Taiwan.

PMID- 12214582
TI  - Trisomies 8 and 9 not detected with fish in patients with mastocytosis.
AB  - Mastocytosis is a rare disease characterized by proliferation of mast cells in
      one or several organs. With conventional cytogenetics about 35% of the patients
      have chromosomally abnormal clones in bone marrow cells. It has been proposed to
      include the mast cell disease among the myeloproliferative disorders, in which
      trisomy for chromosome 8 and 9 can appear in the bone marrow cells. In this study
      bone marrow cells from eight patients with mastocytosis, two had as well an
      associated hematological disease, have been examined with fluorescence in situ
      hybridization (FISH) for enumeration of chromosome no8 and 9. In conventional
      cytogenetics two patients had clones with del(20) and 47,XY,+14/45, X,-Y,
      respectively. None of the patients with mastocytosis had clones with trisomy 8 or
      9 with either cytogenetics or FISH.

PMID- 12214580
TI  - Assessment of a relative therapeutic index between inhaled formoterol and
      salbuterol in asthma patients.
AB  - OBJECTIVE: To quantify the relation between local and systemic magnitudes of
      effects of inhaled formoterol and salbutamol. METHODS: Twenty-eight stable
      asthmatic patients completed this double-blind, randomised crossover study. Pre
      drug administration FEV1 (mean 2.08 L) was 49-93% of predicted and reversibility
      16-82% after inhalation of salbutanmol. Patients inhaled three single doses of
      formoterol fumarate dihydrate (Oxis) (delivered doses of 4.5, 18 and 54 microg)
      via Turbuhaler, two single doses of salbutamol (200 and 1800 microg) via a
      pressurised metered dose inhaler (pMDI) and placebo at intervals of 48 h or more.
      Individual maximum FEV1 and minimum S-K+ were calculated. A classic sigmoid model
      of log-dose response was used to discriminate pharmacologically between
      formoterol and salbutamol. Relative local (maximum FEV1) and systemic (minimum S
      KC) dose potencies, and their ratio, the relative therapeutic index, were
      estimated using an on-linear mixed effect model. RESULTS: The drug effects were
      well tolerated and dose dependent The bronchodilating effect was on a part of the
      dose response curve that could be well approximated by a log-linear function, the
      serum potassium suppressing effect sometimes was not (the lowest doses differed
      only marginally from placebo). Thus, a log-linear approximation was used to
      describe bronchodilation, whereas a sigmoid approximation was more apt to
      describe the decrease in serum potassium concentration. A bivariate dose-response
      model based on these principles was fitted simultaneously to all data. The mean
      relative therapeutic index was estimated to be 2.5 (95%confidence interval: 0.9
      6.5). CONCLUSIONS: The mean relative therapeutic index between formoterol (Oxis)
      4.5-54 microg given via Turbuhaler and salbutamol 200-1800 microg given via pMDI
      was estimated to 2.5 in favour of formoterol; this trend was not statistically
      significant.

PMID- 12214584
TI  - Rituximab-induced serum sickness.

PMID- 12214583
TI  - Hydroxyurea treatment of sickle cell anemia in hospital-based practices.
AB  - In a published randomized clinical trial, hydroxyurea (HU) improved clinical
      outcomes in patients with sickle cell anemia (SCA). The mean treatment duration
      of that trial was 21 months. Here we attempt to determine whether the benefits
      associated with HU therapy of SCA have led also to successful patient acceptance
      of HU treatment in community practices, and whether successful clinical outcomes
      persist beyond 2 years. This is an observational retrospective chart study of the
      computerized medical records of 60 men and women with SCA who had HU treatment
      for at least 3 months and who were treated at teaching hospital subspecialty
      clinics in Baltimore, Maryland, and Washington, D.C. Thirty had remained on
      therapy for at least 24 months. Admissions declined in this group by 30% (P =
      0.04). Declines were seen also in transfusion requirements (-58%, P = 0.07). In
      17 of these 30 patients, at least 48 months of follow-up records were available.
      Fourteen of these remained on therapy the entire period, with similar and
      sustained reductions in admissions and transfusions. We conclude that hydroxyurea
      therapy of SCA applied in community settings leads to declining admissions and
      transfusion rates in many individuals for 4 years or more.

PMID- 12214585
TI  - [Clinic-radiographic correlation. Case 7/2002 - Instituto do Coracao do Hospital
      das Clinicas da FMUSP].

PMID- 12214586
TI  - [Immediate exercise test in patients with chest pain in the emergency
      department].

PMID- 12214587
TI  - Comment on normal hip joint contact pressure distribution in single-leg standing
      effect of gender and an atomic parameters.

PMID- 12214589
TI  - The drug pipeline starts filling up again.

PMID- 12214590
TI  - First anti-CCR5 drug.

PMID- 12214591
TI  - One as potent as five.

PMID- 12214592
TI  - NNRTI without the rash.

PMID- 12214593
TI  - So what infected the chimpanzee?

PMID- 12214594
TI  - Recombinant virus at work.

PMID- 12214595
TI  - California dental clinics.

PMID- 12214596
TI  - Global warming-- effects on plants.

PMID- 12214597
TI  - Clinical quiz. Maternal chronic bilateral nephropathy.

PMID- 12214598
TI  - thrombophilia in childhood hemolytic uremic syndrome.

PMID- 12214599
TI  - Chromosomal clustering of muscle-expressed genes in Caenorhabditis elegans.
AB  - Chromosomes are divided into domains of open chromatin, where genes have the
      potential to be expressed, and domains of closed chromatin, where genes are not
      expressed. Classic examples of open chromatin domains include 'puffs' on polytene
      chromosomes in Drosophila and extended loops from lampbrush chromosomes. If
      multiple genes were typically expressed together from a single open chromatin
      domain, the position of co-expressed genes along the chromosomes would appear
      clustered. To investigate whether co-expressed genes are clustered, we examined
      the chromosomal positions of the genes expressed in the muscle of Caenorhabditis
      elegans at the first larval stage. Here we show that co-expressed genes in C.
      elegans are clustered in groups of 2-5 along the chromosomes, suggesting that
      expression from a chromatin domain can extend over several genes. These
      observations reveal a higher-order organization of the structure of the genome,
      in which the order of the genes along the chromosome id correlated with their
      expression in specific tissues.

PMID- 12214600
TI  - Case-cohort study of styrene exposure and ischemic heart disease.
AB  - Recent epidemiologic studies have consistently reported increased daily
      mortalities and hospital admissions associated with exposure to particulate air
      pollution. Ischemic heart disease (IHD*, International Classification of
      Diseases, Eighth Revision [ICD-8], codes 410-414) is among those diseases that
      contribute in large measure to this excess mortality. Some occupational studies
      have suggested elevated risk of IHD among workers exposed for short periods to
      styrene, which can be emitted from fossil fuel combustion, aircraft exhausts, and
      motor vehicle exhausts. Styrene is found in ambient air at average concentrations
      of a few micrograms per cubic meter or less but may reach very high
      concentrations at particular locations and times. Unmeasured aerosols of styrene
      may also increase population exposures. This case-cohort study explored a
      possible association and dose-response relation between styrene exposure and risk
      of acute IHD in an occupational setting. The population under study was 6587 male
      workers employed between 1943 and 1982 in two US plants manufacturing styrene
      butadiene polymers used in synthetic rubber. The study assessed all 498 subjects
      who died from IHD along with a subcohort of twice that size, 997 subjects,
      selected as a 15% random sample of the full target cohort. IHD deaths during the
      study led to some overlap between cases and the subcohort, leaving 1424 unique
      subjects. Job histories were collected for all subjects. Industrial hygienists
      and engineers from the industry estimated relative exposures for all jobs.
      Exposure data were collected for many of the jobs from different sources. For any
      job with no available exposure measurements, z scores were used to estimate job
      exposure in each plant from the relative exposure level for that job in similar
      plants and the measurement distribution parameters of the study plant.
      Standardized mortality ratio (SMR) analyses were used to examine the overall risk
      of dying from IHD among study subjects compared with the US general population. A
      significantly elevated SMR of 1.47 with a 95% confidence interval (95% CI) of
      1.17 to 1.77 for chronic IHD was found among black workers who had left the
      plants. A modification of the Cox proportional hazard regression model was used
      to control for confounders and examine dose-response relations between styrene
      exposure and the risk of IHD. Employment time-weighted average (TWA) styrene
      concentration intensity for the most recent 2 years was found significantly
      associated with death from acute IHD among active workers with a relative hazard
      of 3.26 to 6.60, depending on duration of employment. In this analysis, the
      highest relative hazard of 6.60 (95% CI, 1.78-24.54) was among active workers who
      had been employed for at least 5 years. The results suggest that the exposure
      intensity was more important than duration of exposure. On the basis of the dose
      response relation established in this study, we estimate that for each 10
      microg/m3 increase in ambient styrene, acute IHD mortality might increase 0.4%.
      At normal ambient styrene levels, the relative risk would be increased, at most,
      0.1% compared with no exposure. At certain locations and times, however, ambient
      styrene could reach levels that would result in a relative hazard for acute IHD
      mortality as high as 3.386-fold the risk at no exposure.

PMID- 12214601
TI  - [The brief history of Korean traditional medicine (1899-1999)].
AB  - Since Korea had opened her ports to foreign forces, the typically royal system of
      her traditional medicine started to turn its attention more to a modernized and
      folk-focused one. After the Kap-oh Reformation (1884) had ended in vain, under
      the spirit of the 'Eastern mind in Western frame' that gained influence during
      Kwang-moo Reformation (1896-1905), Euihakguanje (1899) and Euisagyuchik (1900)
      were decreed to find reciprocal support between Eastern and Western medical
      science. It was the reflection of the independent will Korean medical devotes to
      reply to the swirling changes around the country. However, the Japanese rule
      (1910-1945) would not allow the survival of the inherited medicine of the colony
      and the Korean cure system could only persist as folk remedies. The situation
      didn't get better in the post-liberation years when the Western medical system
      that had found its secure base of growth under the Japanese government continued
      to keep its privilege while the original Korean medicine failed to recover its
      dominance. The law of medicine provided qualification of Oriental doctors but the
      nominal regulation without any administrational support has been far from being
      practical. Thus, the history of Oriental medicine in Korea after 1945 has been
      all but strife. To outline the past hundred years of Korean medicine briefly, it
      has a chance of renovation during the modernization oriented years (1882 - 1910);
      suffered under the severe restraint of imperial control (1910 - 1945); strived to
      build legal and structural background after the liberation (1945 - 1970); and has
      been fighting to regain its authority since the democratic wave of the eighties
      (1980 -1999). Conflict struggle in the 20th century shall be resolved into
      harmony in the beginning century of a new millennium. Medicine also will find
      warm ground of compatibility and bear 'the 3rd medicine.' All who are devoted to
      healthy welfare of people should find their responsibility of connecting the
      forgotten lines of the national medicine and upon the regained tradition, proudly
      developing it into a universal system of cure.

PMID- 12214602
TI  - [Authors of "Classified Collection of Medical Prescriptions"].
AB  - In this study, the career and official ranks of the authors of the Sejong text
      (1443-1445), Sejo text (1451-1464), and Seongjong text (1475-1477) of "Classified
      Collection of Medical Prescriptions" were investigated. In the completion of
      Sejong text, Kim Rye-mong (1406-1469), Ryu Seong-won (?-1456), and Min Bohua (?)
      collected and arranged all medical books inside and outside of Choseon; Kim Moon
      (?-1448), Shin Seok-jo (1407-1459), Lee Ye (1419-1480), Kim Soo-on (1410-1481),
      Jeon soon-eui (?), Choi Yun (?), and Kim Yu-ji (?-1469) took part in the edition;
      Lee Yong (1418-1453), Lee Sa-cheol (1405-1456), Lee Sa-soon (?-1455), and Rho
      Joon-g-rye (?-1452) participated in the editorial supervision. Ryang Seong-ji
      (1415-1482), Son So (1433-1484), Ryu Yo (?), Han Chi-ryang (?), An Geuk-sang (?),
      Han Kye-mi (1421-1471), and Choi Young-rin (?) took part in the completion of
      Sejo text. Han Kye-heiu (1423-1482), Rym Won-joon (1423-1500), Kueon Chan (1430
      1487), Ryu Seo (?), and Baek Soo-heui(?) participated in the completion of
      Seongjong text. All 96 persons participated in the completion of draft text,
      revision text, and first-publication text of "Classified Collection of Medical
      Prescriptions". 14 persons (14.58%) participated in the completion of draft text.
      77 persons (80.21%) participated in revision text, and 5 persons (5.21%)
      participated in first-publication text. Even though "Classified Collection of
      Medical Prescriptions" is a medical book, civil officials participated in its
      completion together with medical officials. The scholars of Jiphyeonjeon (The
      Jade Hall of Scholars) who led the academy at those days and famous medical
      officials were ordered to complete it by Sejong (1419-1450), Sejo (1455-1468),
      and Seongjong (1470-1494) who showed special interest in their own health and the
      health of common people.

PMID- 12214603
TI  - [The equipment of using Azolla for O2-supplementation (correction of
      supplimentation) and its test].
AB  - The equipment of using Azolla for O2-supplementation and food-production in
      future space station was developed and tested. Dog was used as the O2-consuming
      animal. The design of this device considered both the requirement of Azolla
      growth, such as illumination, temperature, humidity, nutrition and biomass
      harvesting, and also the food supplement, excretion draining and temperature
      controlling for the dog under the condition of an airtight chamber for a
      relatively long duration. This device was preliminarily tested for O2-release by
      Azolla, and data about O2-supplement by Azolla were obtained.

PMID- 12214604
TI  - [Development of a ground-based experimental facility for space cultivation of
      higher plant].
AB  - A ground-based experimental facility was developed for conducting initial ground
      based simulation study of Controlled Ecological Life Support System (CELSS). The
      facility is composed of a main chamber, O2 and CO2 composition control
      subsystems, plant cultivation subsystem and whole data management subsystem. The
      growth room, being composed of a inner wall of mirror-face stainless steel, holds
      a volume of 1.8 m3 and a growing area of 1.2 m2; electronic fluorescent lamps
      were used as lighting sources and polyvinyl formal was used for root matrixes;
      the environmental parameters of the growing room such as temperature, relative
      humidity, O2 concentration, CO2 concentration, lighting period and irradiance
      intensity and the nutrient parameters such as pH, electrical conductivity,
      dissolved oxygen concentration, liquid level of nutrient storage tank and flow
      rate of nutrient were all controlled automatically; all of the above-mentioned
      parameters can be inspected, collected, stored and printed regularly and
      dynamically. The results of a combined debugging and preliminary plant
      cultivation verified that the technical target of the facility had reached its
      initial design requirements, it can be used to conduct ground-based simulation
      studies of space cultivation of higher plants.

PMID- 12214605
TI  - [A fluctuographic analysing of EEG patients with paroxysmal headache].
AB  - OBJECTIVE: To offer reference of the screening procedure for aircrew and
      astronaut selection. METHOD: The competitive frequency-fluctuation
      characteristics of the dominant frequency in the band of 7-12 Hz in EEG and power
      density spectra of alpha band power-fluctuation were analyzed with a newer system
      of electroencephalofluctuographic technology in 20 patients (male 13, female 7,
      aged 17-37 years) with paroxysmal headache. RESULT: During episodes of headache
      in the affected sites the cumulated dominant fluctuation probability of each
      frequency components was in the order of 7, 8, 9, 10, 11, 12 Hz from high to low;
      The relative entropy value was 92.25% +/- 3.41%; Two peaks having at least 25%
      higher value than those of its neighbors were observed at 1.86 mHz and 4.65 mHz
      in power density spectra of power-fluctuation. During the intervals of episodes
      the above-mentioned probability character disappeared; The relative entropy value
      was decreased to 69.08% +/- 4.16% ; A new peak was found at 0.93 mHz in spectra
      power-fluctuation, with a reduction in peak value power at 4.65 mHz. CONCLUSION:
      It not only offered a parameter for pathophysiological and functional evaluation
      of paroxysmal headache, but also provided reference of the screening procedure
      for aircrew and astronaut selection.

PMID- 12214606
TI  - [Exercise ECG test as a method for non-invasive detection of myocardial
      ischemia].
AB  - OBJECTIVE: To improve the exercise ECG analysis for non-invasively detection of
      myocardial ischemia. METHOD: The newly developed measuring system of exercise ECG
      defines ST segment area and STA/HR slope as the new characteristic parameters,
      thus can sensitively detect myocardial ischemia. Some methods were proposed to
      reduce noise and artifacts for effective sampling of exercise ECG. RESULT: 14
      exercise ECG records were sampled and analyzed in clinical exercise test. It was
      found that the new parameters are very effective and sensitive to myocardial
      ischemia. The results show that the method is reliable and stable. CONCLUSION:
      The method improves one of the evaluating indexes of exercise ECG analysis. It is
      quite promising for clinical application in future.

PMID- 12214607
TI  - [Effects of rotating-table simulated "push-pull maneuver" on cerebral circulation
      function].
AB  - OBJECTIVE: To investigate the change and regulation of cerebral circulation
      during rotating-table simulated push-pull maneuver. METHOD: A special rotating
      table was used to simulate the push-pull maneuver. 10 healthy adults were
      subjected to a series of "head-up stand (+1Gz) 1 min head-down stand (-1Gz) 10 s
      and head-up stand (+1Gz) 1 min" changes. Cerebral blood flow velocity and
      pulsatility indices in the left middle cerebral artery were constantly measured
      with a TC2020TCD using Transcranial Doppler [correction of Transcanial Dopplor]
      instrument. RESULT: During 10 s head-down stand (-1Gz) systolic velocity (Vs)
      increased, diastolic velocity (Vd) decreased, and the pulsatility indices (PI and
      RI) increased significantly in the left middle cerebral artery. During subsequent
      head-up stand (+1Gz), these changes didn't resume immediately and maintained for
      at least 20 s. CONCLUSION: This result implied that the push-pull maneuver
      increased the resistance of the cerebral vessels, which might be one of the
      mechanisms of the push-pull effect.

PMID- 12214608
TI  - [Hemodynamic changes of pulmonary circulation during HDT -30 degrees].
AB  - OBJECTIVE: To study the hemodynamic changes of pulmonary circulation during
      simulated weightlessness. METHOD: 12 subjects were studied using echocardiography
      and electrocardiography during head-down tilt (HDT) of -30 degrees lasting for 45
      min. RESULT: Right ventricular ejection time increased significantly (P<0.05);
      peak velocity of pulmonary arterial blood flow decreased significantly (P<0.05);
      acceleration time of pulmonary arterial blood flow did not change significantly;
      significant decrease of right ventricular output occurred at the 10th minute and
      the 30th minute (P<0.05); pre-ejection period significantly decreased at the 30th
      minute and recovery. Heart rate, mean velocity of pulmonary arterial blood flow,
      and acceleration of pulmonary arterial blood flow did not change significantly;
      left ventricular cardiac output, stroke volume and blood pressure remained
      constant throughout the experiment. CONCLUSION: Changes of the parameters of
      pulmonary circulation suggested that pulmonary resistance increased, and the
      increase of pulmonary resistance maybe be the direct cause of the increase of
      pulmonary arterial pressure.

PMID- 12214609
TI  - [An analysis on thickness effect of lithium fluoride detector in proton
      measurement].
AB  - OBJECTIVE: To theoretically analyze the thickness effect of a LiF detector for
      proton measurement. METHOD: Thickness effect of the detector was calculated by
      using the definition of the detector dose under ideal and reasonable hypothesis.
      RESULT: The thickness effect of the detector was not obvious when protons could
      penetrate the detector: when proton energy was above 12 MeV, the thickness effect
      was obvious only on condition that the detector thickness approaches proton
      range, when proton energy was less than 12 MeV, the thickness effect was not
      obvious. The thickness effect of the detector was obvious, when protons could not
      penetrate the detector. CONCLUSION: Thin detectors should be used in low energy
      proton measurements to avoid thickness effect of the detector.

PMID- 12214610
TI  - [Effect of ascorbic acid on chemiluminescence of cells cultivated in various
      concentration of oxygen].
AB  - OBJECTIVE: To investigate the effect of Vitamin C (Vit. C) on the stimulated
      chemiluminescence of rabbit's pulmonary alveolus macrophage (AM) cultivated in
      various concentration of oxygen. METHOD: The AMs from rabbits were cultured in a
      thermostat in which luminescence from cells can be examined, then air with
      various concentrations of oxygen were continuously led in the device and the AM's
      stimulated chemiluminescence by PMA (phorbol myristate acetate) was measured with
      a chemiluminometer. RESULT: In the air with 0.5% O2, AM's survival rate and
      luminescence level were only 50% or 45% of the values before the exposure, and
      were reducing progressively with increasing dose of Vit. C in the culture medium.
      To increase the concentration of oxygen in the air was advantageous in enhancing
      cell's vitality and it can partly counteract the decrease of AM's stimulated
      chemiluminescence level by adding Vit. C into the culture medium. CONCLUSION:
      Oxygen in the air is important for cultivated cell's luminescence and survival,
      and it could lead to grave damage to the cultivated AMs when there is high
      concentration of Vit. C in the culture medium.

PMID- 12214611
TI  - [Material selection and structural design of simulated space module for field].
AB  - OBJECTIVE: To select the suitable material for the structure of simulated space
      cabin to meet the special requirements which the unitary metallic material cannot
      do. METHOD: The structural material was selected through comparison between the
      mechanical properties of fiber reinforced plastics (FRP) and a few conventional
      metallic materials. The content and arrangement of the fibers in the composite
      material were suitably designed according to load condition and structural shape
      of the cabin. RESULT: High strength and high stiffness, light weight, anti
      fatigue and shock proof were achieved for the whole module structure. It meets
      the medical and hygienic standard for hazardous gases. CONCLUSION: The structural
      design of fiber glass reinforced plastics composite module was proved to be
      successful. It reduced the weight of the module body, and increased the strength
      and toughness of the whole module.

PMID- 12214612
TI  - [Effects of heat and noise environments on lipid peroxidation erythrocyte
      membrane in pilots].
AB  - OBJECTIVE: To investigate the effects of heat and noise environments on lipid
      peroxidation of erythrocyte membrane in pilots. METHOD: Twenty-four pilots and
      twenty-one ground personnel (control group) served as the subjects. The pilots
      performed flying in heat and noise environments. Glutathione peroxidase (GSHpx)
      and malondialdehyde [correction of malondiadehyde] (MDA) levels in erythrocyte
      membrane were determined before flying (6:00 a.m.), immediately after flying
      (12:00 a.m.) and 8 hours after flying (8:00 p.m.) respectively with a
      spectrophotometer. RESULT: Immediately after flying, GSHpx activity in pilot's
      erythrocyte membrane decreased significantly as compared with that in control
      group. Immediately after flying and 8 h after flying, MDA contents in pilots
      increased significantly as compared with that of control group. CONCLUSION: Heat
      and noise environments might induce increase of lipid peroxidation reaction and
      decrease of antioxidant ability.

PMID- 12214613
TI  - [Effects of acute hypobaric hypoxia on the distribution of somatostatin contents
      in lower gastrointestinal tract of rats].
AB  - OBJECTIVE: To examine the effects of acute hypobaric by hypoxia on the
      distribution of Somatostatin (SS) contains in lower gastrointestinal tract of
      rats. METHOD: 36 Wistar [correction of Wister] male rats were divided into 6
      groups. Three were control groups, three were ulcerous groups. Each group
      contains ground, 5000 m above sea level and 10000 m above sea level. SS contents
      were determined with radioimmunoassay [correction of radioimmunoassy] methods.
      RESULT: Statistically significant difference was exhibited among each group.
      There was no significant difference of SS contents in each altitude between model
      and control. SS contents were significantly increased in intestine of control in
      5000 m groups, in caecum in 5000 m groups, compared with that in ground (P<0.05).
      It was also significantly increased in intestine of model in 5000 m groups, in
      caecum in 5000 m groups, compared with that in ground (P<0.01). SS contents was
      significantly increased in caecum of model in 10000 m groups compared with that
      in ground (P<0.05). Except this, There was no significant difference of ss
      contents in lower gastrointestinal tract among each group. CONCLUSION: SS
      contents in lower gastrointestinal tract were significantly increased in acute
      hypobaric hypoxia rats. This result suggested that ss contents in lower
      gastrointestinal tract may play an important protective role in acute hypobaric
      hypoxia rats.

PMID- 12214614
TI  - [Sensorineural deafness and aerospace flight].
AB  - OBJECTIVE: To probe the relations between sensorineural deafness and flying in
      aviation or space. METHOD: Case studies of sensorineural deafness were made in 36
      pilots. RESULT: Unilateral deafness (n=15) and bilateral deafness (n=21) were
      found in 36 pilots, with mild deafness (n=9), moderate deafness (n=37) and severe
      deafness (n=11) in 57 ears. 19 cases were permanently grounded and 17 cases were
      still in a qualified position to continue their flying job. CONCLUSION:
      Sensorineural deafness may hazard the flying in aviation or space, meanwhile the
      flying in aviation or space may lead to or aggravate sensorineural deafness.

PMID- 12214615
TI  - [Measurement and evaluation of visual index in VDT operators under Multi-user
      system].
AB  - OBJECTIVE: To evaluate the visual function of the visual display terminal (VDT)
      operators under the Multi-user system. METHOD: Subjective symptoms of the VDT
      operators under the Multi-user system were measured before and after work in the
      field study. Visual indices were measured at 8:15, 9:15, 10:15, 11:15, or 12:15
      a.m. RESULT: No discomfort symptom was observed during the working time, and
      Longitudino-Kinetic visual acuity, and Critical flicker frequency didn't
      decrease. Refraction showed no significant decrease as compared with that at 8:15
      except that of right eye measured at 12:15. CONCLUSION: The Visual function of
      the VDT operators remained good in the Multi-user's system.

PMID- 12214616
TI  - [Influence of weightlessness on water and electrolytes balance in body].
AB  - The balance of water and electrolytes plays an important role in enabling the
      human body to adapt to spaceflight. This paper introduced the research methods,
      and changes in water and electrolytes balance during and after space flight. The
      mechanism and the hazard of the disorder of water and electrolytes caused by
      weightlessness were discussed.

PMID- 12214617
TI  - [Weightlessness and heat stress on astronauts].
AB  - Thermal emergency situations have more than once been encountered since the
      beginning of manned space flights in 1961. This article contemplates human
      thermal tolerance in weightlessness as complicated with headward [correction of
      headword] fluid shifts, plasma volume loss, cardiovascular deconditioning,
      reduced exercise capacity and energy metabolism changes, etc. With these
      considerations, it is necessary to further investigate the thermoregulation in
      spaceflight for the health and safety of astronauts.

PMID- 12214618
TI  - [CAT system and its application in training for manned space flight].
AB  - As aerospace missions get increasingly frequent and complex, training becomes
      ever more critical. Training devices in all levels are demanded. Computer-Aided
      Training (CAT) system, because its economic, efficient and flexible, is
      attracting more and more attention. In this paper, the basic factors of CAT
      system were discussed; the applications of CAT system in training for manned
      space flight were illustrated. Then we prospected further developments of CAT
      system.

PMID- 12214619
TI  - Mortality, functional status both important in assessing hip fracture care.

PMID- 12214620
TI  - Guide addresses unique aspects of care for women with HIV.

PMID- 12214621
TI  - Benchmarking project spurs better guideline adherence.

PMID- 12214622
TI  - IOM report: healthcare system shortchanges dying cancer patients.

PMID- 12214623
TI  - Estrogen-receptor polymorphism and hormone-replacement therapy.

PMID- 12214624
TI  - Treatment of migraine.

PMID- 12214625
TI  - Treatment of migraine.

PMID- 12214626
TI  - Treatment of migraine.

PMID- 12214627
TI  - Treatment of migraine.

PMID- 12214628
TI  - Treatment of migraine.

PMID- 12214629
TI  - Schistosomiasis.

PMID- 12214630
TI  - Schistosomiasis.

PMID- 12214631
TI  - Nonalcoholic fatty liver disease.

PMID- 12214632
TI  - Nonalcoholic fatty liver disease.

PMID- 12214633
TI  - Nonalcoholic fatty liver disease.

PMID- 12214634
TI  - A method for calculating proton-nucleus elastic cross-sections.
AB  - Recently [Nucl. Instr. and Meth. B 145 (1998) 277; Extraction of in-medium
      nucleon-nucleon amplitude from experiment, NASA-TP, 1998], we developed a method
      of extracting nucleon-nucleon (N-N) cross-sections in the medium directly from
      experiment. The in-medium N-N cross-sections form the basic ingredients of
      several heavy-ion scattering approaches including the coupled-channel approach
      developed at the NASA Langley Research Center. We investigated [Proton-nucleus
      total cross-sections in coupled-channel approach, NASA/TP, 2000; Nucl. Instr. and
      Meth. B 173-174 (2001) 391] the ratio of real to imaginary part of the two body
      scattering amplitude in the medium. These ratios are used in combination with the
      in-medium N-N cross-sections to calculate proton-nucleus elastic cross-sections.
      The agreement is excellent with the available experimental data. These cross
      sections are needed for the radiation risk assessment of space missions.

PMID- 12214635
TI  - Critical evaluation of factors required to terminate the postclosure monitoring
      period at solid waste landfills.
AB  - Regulations governing the disposal of solid waste in landfills specify that they
      must be monitored for 30 years after closure unless this period is extended by
      the governing regulatory authority. Given the wide range of conditions under
      which refuse is buried, technical criteria, rather than a specific time period,
      are preferable for evaluation of when it is acceptable to terminate postclosure
      monitoring. The objectives of this paper are to identify and evaluate parameters
      that can be used to define the end of the postclosure monitoring period and to
      present a conceptual framework for an investigation of whether postclosure
      monitoring can be terminated at a landfill. Parameters evaluated include leachate
      composition and leachate and gas production. Estimates of leachate production
      from closed landfills are used to assess the potential environmental impacts of a
      hypothetical release to surface water or groundwater. The acceptability of
      gaseous releases should be evaluated against criteria for odors, the potential
      for subsurface migration, and greenhouse gas and ozone precursor emissions. The
      approach presented here must be tested on a site-specific basis to identify
      additional data requirements and regulatory activity that might be required to
      prepare regulators for the large number of requests to terminate postclosure
      monitoring expected over the next 20 years. An approach in which the frequency
      and extent of postclosure monitoring is reduced as warranted by site-specific
      data and impact analysis should provide an effective strategy to manage closed
      landfills.

PMID- 12214636
TI  - Influence of population density and temporal variations in emissions on the air
      duality benefits of NOx emission trading.
AB  - Ozone formation is a complex function of local hydrocarbon and nitrogen oxide
      emissions. Therefore, trading of NOx emissions among geographically distributed
      facilities can lead to more or less ozone formation than across-the-board
      reductions. Monte Carlo simulations of trading scenarios involving 51 large NOx
      point sources in eastern Texas were used in a previous study by the authors to
      assess the effects of trading on air quality benefits, as measured by changes in
      ozone concentrations. The results indicated that 12% of trading scenarios would
      lead to greater than a 25% variation from conventional across-the-board
      reductions when air quality benefits are based only on changes in ozone
      concentration. The current study found that when benefits are based on a metric
      related to population exposure to ozone, two-thirds of the trading scenarios lead
      to changes in air quality benefits of approximately 25%. Variability in air
      quality benefits is not as strongly dependent on the temporal distribution of NOx
      emissions.

PMID- 12214637
TI  - Atmospheric transport of toxaphene from the southern United States to the Great
      Lakes Region.
AB  - Toxaphene was used extensively as an insecticide on cotton in the southern United
      States until its use was restricted in 1982. Toxaphene has been found in the
      water and fishes from the Great Lakes, and several authors have qualitatively
      linked this observation to atmospheric transport from the southern United States,
      although no detailed field study has been done to confirm this suggestion. We
      implemented a sampling network to measure the gas-phase concentrations of
      toxaphene near Lake Michigan at Sleeping Bear Dunes, MI; Bloomington, IN;
      Lubbock, TX; and Rohwer, AR. The toxaphene concentrations referenced to 288 K
      were 11 +/- 1, 25 +/- 1, 160 +/- 3, and 950 +/- 30 pg/ m3, respectively. We
      combined these concentration data with a nonparametric, backward trajectory,
      multiple regression model of the following form: ln(P) = a0 + a1/T + a2theta
      where P is the partial pressure of toxaphene (in atm) in a given sample, T is the
      atmospheric temperature at the sampling site during sampling (in degrees Kelvin),
      and theta is 0 if the backward trajectory comes from the north and 1 if the
      trajectory comes from the south. The parameters of this model were generally
      significant, giving a temperature coefficient (a1) corresponding to 45 +/- 8
      kJ/mol and a positive directional coefficient (a2) of 0.6 +/- 0.2 (except for
      Texas, which was not significant). The positive sign and magnitude of the
      directional coefficient indicates that the sources of toxaphene are located south
      of the sampling sites. We also compared the chemical behavior of toxaphene in the
      atmosphere and found that the congener ratios were similar at the different
      sampling sites but slightly different from various toxaphene standards.

PMID- 12214638
TI  - Phototransfomation of ticlosan in surface waters: a relevant elimination process
      for this widely used biocide--laboratory studies, field measurements, and
      modeling.
AB  - The phototransformation of the widely used biocide triclosan (5-chloro-2-(2,4
      dichlorophenoxy)phenol) was quantified for surface waters using artificial UV
      light and sunlight irradiation. The pH of surface waters, commonly ranging from 7
      to 9, determines the speciation of triclosan (pKa = 8.1) and therefore its
      absorption of sunlight. Direct phototransformation of the anionic form with a
      quantum yield of 0.31 (laboratory conditions at 313 nm) was identified as the
      dominant photochemical degradation pathway of triclosan. Combining the
      photochemical parameters with actual meteorological data and field measurements
      allowed us to validate a model describing the behavior of triclosan in the water
      column of a Swiss lake (Lake Greifensee). From August to October 1999, direct
      phototransformation accounted for 80% of the observed total elimination of
      triclosan from the lake. The remaining major sink for triclosan was the loss in
      the outflow. Thus, during the summer season, direct phototransformation appears
      to be a major elimination pathway of triclosan in this lake. Based on absorption
      spectra and quantum yield data, the phototransformation half-lives of triclosan
      were calculated under various environmental conditions typical for surface
      waters. Daily averaged half-lives were found to vary from about 2 to 2000 days,
      depending on latitude and time of year.

PMID- 12214639
TI  - Polychloronaphthalenes and other dioxin-like compounds in Arctic and Antarctic
      marine food webs.
AB  - Here we report accumulation patterns of polychlorinated naphthalenes (PCNs),
      polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs),
      polychlorinated biphenyls (PCBs), and pesticides (HCB, p,p'DDE) in polar
      organisms (polar bear from Alaskan Arctic and krill, sharp-spined notothen,
      crocodile icefish, Antarctic silverfish, Adelie penguin, South polar skua, and
      Weddell seal from the Ross Sea, Antarctica). PCNs, found in most of the samples,
      ranged from 1.5 pg/g in krill to 2550 pg/g in South polar skua on a wet weight
      basis. Lower chlorinated PCNs were the predominant congeners in organisms except
      skua and polar bear that showed similar PCN homologue patterns. PCDD/F
      concentrations were <90 pg/g wet wt in polar organisms; PCDD congeners showed
      peculiar accumulation patterns in different organisms. Correlation existed
      between PCN and PCB concentrations. PCB, HCF, and p,p'DDE levels were the highest
      in skua liver (11,150 ng/g wet wt, 345 ng/g wet wt, and 300 ng/g wet wt,
      respectively). Contribution of PCNs to 2,3,7,8-tetrachlorodibenzo-p-dioxin
      equivalents (TEQ) was negligible (<0.1%) because of the lack of most toxic
      congeners. The highest TEQ was found in South polar skua liver (45 pg/g, wet
      weight). This is the first study to document the occurrence of PCNs in Antarctic
      organisms. High levels of dioxin-like chemicals in skua suggest the importance of
      intake via diet and migration habits, thus POP detection can be useful to trace
      migration behavior. Moreover, POP concentrations in penguin and skua eggs prove
      their transfer from the mother to eggs.

PMID- 12214640
TI  - Fractionation of natural organic matter in drinking water and characterization by
      13C cross-polarization magic-angle spinning NMR spectroscopy and size exclusion
      chromatography.
AB  - Natural organic matter from drinking water sources was fractionated, and the
      fractions were characterized by NMR and SEC with the aim of relating NOM
      structure to treatability. Organic matter was isolated from two Australian
      surface waters (Horsham, Moorabool) by reverse osmosis and from a groundwater
      (Wanneroo) by anion exchange. The isolates were fractionated according to
      polarity and charge by resin adsorption. 13C NMR spectra of the freeze-dried
      fractions showed the most hydrophobic fraction to be high in aliphatic and
      aromatic carbon while slightly hydrophobic organics have more carbonyl and
      alkoxyl carbon. The Horsham and Wanneroo hydrophilic fractions show strong
      alkoxyl signals attributed to carbohydrate. Moorabool hydrophilics contain
      aromatic (phenolic) carbon; the apparent absence of carbohydrate appears to be an
      artifact. Size-exclusion chromatograms were recorded on the original and
      fractionated organics with both UV and dissolved organic carbon detection. The
      Horsham and Moorabool organics have similar molecular size distributions while
      Wanneroo is dominated by strongly absorbing species having large hydrodynamic
      radii. The hydrophobic and charged hydrophilic fractions also have high apparent
      MW, while the neutral fraction is higher in low-MW compounds of relatively low
      specific absorbance, suggestive of carbohydrates.

PMID- 12214641
TI  - Association of uranium with iron oxides typically formed on corroding steel
      surfaces.
AB  - Decontamination of metal surfaces contaminated with low levels of radionuclides
      is a major concern at Department of Energy facilities. The development of an
      environmentally friendly and cost-effective decontamination process requires an
      understanding of their association with the corroding surfaces. We investigated
      the association of uranium with the amorphous and crystalline forms of iron
      oxides commonly formed on corroding steel surfaces. Uranium was incorporated with
      the oxide by addition during the formation of ferrihydrite, goethite, green rust
      II, lepidocrocite, maghemite, and magnetite. X-ray diffraction confirmed the
      mineralogical form of the oxide. EXAFS analysis at the U L(III) edge showed that
      uranium was present in hexavalent form as a uranyl oxyhydroxide species with
      goethite, maghemite, and magnetite and as a bidentate inner-sphere complex with
      ferrihydrite and lepidocrocite. Iron was present in the ferric form with
      ferrihydrite, goethite, lepidocrocite, and maghemite; whereas with magnetite and
      green rust II, both ferrous and ferric forms were present with characteristic
      ferrous:total iron ratios of 0.65 and 0.73, respectively. In the presence of the
      uranyl ion, green rust II was converted to magnetite with concomitantreduction of
      uranium to its tetravalent form. The rate and extent of uranium dissolution in
      dilute HCl depended on its association with the oxide: uranium present as
      oxyhydroxide species underwent rapid dissolution followed by a slow dissolution
      of iron; whereas uranium present as an inner-sphere complex with iron resulted in
      concomitant dissolution of the uranium and iron.

PMID- 12214642
TI  - On-line analysis of urban particulate matter focusing on elevated wintertime
      aerosol concentrations.
AB  - A 10-day winter sampling campaign was conducted in downtown Toronto for
      particulate matter (PM) air pollution in the fine (<2.5 microm) size range. An
      aerosol laser ablation mass spectrometer (LAMS), a tapered-element oscillating
      microbalance (TEOM), and an aerodynamic particle sizer (APS) were operated in
      parallel to characterize the PM on-line. In this study, the LAMS observed
      differences in the chemical composition between three separate episodes with
      higher PM2.5 mass and APS counts. LAMS results showed that in one instance of
      elevated PM, organic amines were present in the particulates. Temporal analyses
      of this episode revealed chemical transformations as the amines, characterized by
      m/z peaks 58(C3HeN)+, 86(C5H2N)+, and nitrates, increased in number concentration
      while Ca and hydrocarbon particle classes concurrently decreased. On another day,
      sulfates were found to have increased significantly. The third event was only 4 h
      in duration and exhibited an increase in the number of submicron-sized
      K/hydrocarbons and sulfate-containing particles. In this last event, the
      hydrocarbons and a K to Fe ratio enrichment indicated there was likely a
      contribution from a combustion source. This work offers some of the first
      insights into single particle size and chemistry in a cold winter climate.

PMID- 12214643
TI  - Adsorption-desorption of phosphate on airborne dust and riverborne particulates
      in East Mediterranean seawater.
AB  - The potential importance of adsorption-desorption behavior of phosphorus (P) on
      the East Mediterranean (E. Med) P cycle was investigated. Contrasting adsorption
      behavior between Saharan dust (SD) and Nile particulate matter (Nile PM) was
      observed. SD was a source of P to the region, which released an average of 3.3 +/
      0.3 micromolP/g into the surface seawater and showed no adsorption ability under
      the conditions close to the E. Med deep water. Saharan dust is therefore unlikely
      to be the reason for P limitation in the region. By contrast, Nile PM acted dual
      roles of a sink and source of P in different waters (surface seawater, deep
      seawater, and river water). A new crossover-type adsorption-desorption model
      explained the contrasting adsorption behavior and the dual nature of natural
      particles. The model indicates that when natural particles are transported
      between different waters, they can be a sink (adsorption) or a source
      (desorption) of phosphorus depending on the "specific concentration (lambda)",
      which is the ratio between the aqueous P concentration and the zero equilibrium P
      concentration (EPC0). EPC0 refers to the solute concentration value where the
      adsorption isotherm crosses over the aqueous concentration axis. When lambda > 1,
      adsorption occurs, whereas when lambda < 1, desorption occurs. The model added a
      general development to the methodology of adsorption isotherm, where, for the
      first time, effects of solute concentration, solid concentration, and aqueous
      medium (EPC0) on the adsorption and desorption of P in natural waters were
      simultaneously described by a single equation. Using the model, it was
      quantitatively reconstructed that particles emitted during the pre-1964 Nile
      floods could be a major source of P to Egyptian coastal waters (up to 4800
      tonsP/yr), greater than the dissolved P flux (approximately 3200 tonsP/yr), but a
      trapper of dissolved phosphate in E. Med deep waters.

PMID- 12214644
TI  - Direct evidence of sequestration in sediments affecting the bioavailability of
      hydrophobic organic chemicals to benthic deposit-feeders.
AB  - In contrast to equilibrium partitioning model (EqP) calculations, biota to
      sediment accumulation factors (BSAF) of hydrophobic organic compounds for deposit
      feeders are highly variable. Recent literature suggests that this variability can
      be attributed to differences in sequestration or the presence of slowly desorbing
      fractions in the sediment. In the present study, we investigated whether the
      observed relationship between bioavailability and sequestration is causal. We
      determined BSAF values and sequestration status, measured as the distribution
      over rapidly and slowly desorbing fractions, of polycyclic aromatic hydrocarbons
      (PAHs) and polychlorinated biphenyls (PCBs) in a manipulated sediment as well as
      in the original, unmanipulated sediment The manipulation, 48 h suspending with
      Tenax, resulted in reduction of the rapidly desorbing fraction, while other
      factors such as contact time and sediment properties remained constant. Contrary
      to expectations based on EqP, BSAF values did not remain constant but were
      reduced by a factor of 2-27, proportional to the reduction in rapidly desorbing
      fractions. The results provide direct evidence of a causal relationship between
      sequestration and bioavailability to deposit-feeders. Furthermore, the present
      study demonstrates the need to modify traditional use of the equilibrium
      partitioning model to account for variation in the sequestration status of HOC in
      sediments.

PMID- 12214645
TI  - Carbon isotope signature of polycyclic aromatic hydrocarbons (PAHs): evidence for
      different sources in tropical and temperate environments?
AB  - In tropical soils, naphthalene and, partly also, perylene occur at elevated
      concentrations while pyrolytic higher molecular weight PAHs are almost absent. We
      hypothesize that there are recent biological PAH sources in the tropical
      environment related with woody plants and termites. We used the C isotope
      signature of individual PAHs in temperate and tropical soils and in tropical wood
      and termite nests to distinguish different PAH sources. The mean delta13C values
      of the benzo[b+j+k]fluoranthenes and of benzo[a+e]pyrenes in temperate soils
      ranged between -24.6/1000 and -25.3/1000, being similar to values reported in the
      literature for PAHs with pyrolitic origin. The mean delta13C values of perylene
      decreased in the order temperate soils (-27.0/1000) > termite nests (-31.4/1000)
      > tropical soil (-32.4/1000), while those of naphthalene (-24.6/1000 to 
      26.2/1000) were similar among the tropical and temperate soils, tropical wood,
      and termite nests. Our results support the assumption that perylene in the
      tropical environment is recently biologically produced, as indicated by the
      depletion in 13C. The C isotope composition of naphthalene, however, cannot be
      used to distinguish different sources.

PMID- 12214646
TI  - Reductive dechlorination of 1,1,2,2-tetrachloroethane.
AB  - Products of the transformation of organic pollutants in the environment are often
      predicted based on the structure of the parent compounds. In some cases, however,
      multiple products may result from the same reaction pathway. In this study, the
      reduction of 1,1,2,2-tetrachloroethane (1,1,2,2-TeCA) is investigated both
      experimentally and computationally. Experimental results and data available in
      the literature reveal that the ratio of Z-1,2-dichloroethylene (Z-DCE) to E-1,2
      dichloroethylene (E-DCE) produced from the reductive beta-elimination of 1,1,2,2
      TeCA is approximately 2:1, and this ratio is independent of the reductant used.
      The exception is iron metal, which results in a ratio of 4.5:1. Computational
      results reveal that the 1,2,2-trichloroethyl radicals (1,1,2-TCA*) formed upon
      the transfer of the first electron are nearly isoenergetic and are in rapid
      equilibrium. Thus, the conformer population of the 1,1,2,2-TeCA does not dictate
      the product distribution. Using Marcus theory, it is demonstrated that the Z:E
      ratio of 2:1 reflects the relative rates of the two possible electron transfer
      steps to the two radical conformers. Further analysis of the thermochemistry of
      the reaction reveals that this ratio of rate constants should be essentially
      independent of the thermodynamic driving force, which is consistent with the
      experimental results. The different observed product distribution when iron metal
      is the reductant is hypothesized to result from an organometallic intermediate.
      The reduction of the 1,1,2,2-TeCA is an overall two-electron process, but the
      fact that the radicals equilibrate at a rate more rapid than the transfer of the
      second electron suggests that reductants employed act as decoupled single
      electron-transfer agents.

PMID- 12214647
TI  - Transformation processes, pathways, and possible sources of distinctive
      polychlorinated dibenzo-p-dioxin signatures in sink environments.
AB  - In recent years, studies on environmental samples with unusual dibenzo-p-dioxin
      (PCDD) congener profiles were reported from a range of countries. These profiles,
      characterized by a dominance of octachlorinated dibenzodioxin (OCDD) and
      relatively low in dibenzofuran (PCDF) concentrations, could not be attributed to
      known sources or formation processes. In the present study, the processes that
      result in these unusual profiles were assessed using the concentrations and
      isomer signatures of PCDDs from dated estuarine sediment cores in Queensland,
      Australia. Increases in relative concentrations of lower chlorinated PCDDs and a
      relative decrease of OCDD were correlated with time of sediment deposition.
      Preferred lateral, anaerobic dechlorination of OCDD represents a likely pathway
      for these changes. In Queensland sediments, these transformations result in a
      distinct dominance of isomers fully chlorinated in the 1,4,6,9-positions (1,4
      patterns), and similar 1,4-patterns were observed in sediments from elsewhere.
      Consequently, these environmental samples may not reflect the signatures of the
      original source, and a reevaluation of source inputs was undertaken. Natural
      formation of PCDDs, which has previously been suggested, is discussed; however,
      based on the present results and literature comparisons, we propose an
      alternative scenario. This scenario hypothesizes that an anthropogenic PCDD
      precursor input (e.g. pentachlorophenol) results in the contamination. These
      results and hypothesis imply further investigations are warranted into possible
      anthropogenic sources in areas where natural PCDD formation has been suggested.

PMID- 12214648
TI  - Kinetics and uptake mechanisms for monomethylmercury between freshwater algae and
      water.
AB  - Uptake kinetics of monomethylmercury chloride (MeHgCl) were measured for two
      species of green algae (Selenastrum capricomutum and Cosmarium botrytis), one
      blue-green algae (Schizothrix calcicola), and one diatom (Thalassiosira
      weissflogii), algal species that are commonly found in natural surface waters.
      Species differences were found with the two green algae giving the highest uptake
      rates, and one of them (Cosmarium) showing differences between cultures having
      widely different cell age (exponential versus stationary), where increases in
      uptake rate for cells 30 days old were about 25 times greater than cells only 3
      days old when weights of cells were considered. Both Schizothrix and
      Thalassiosira exhibited nearly the same lower uptake rates, approximately 20
      times lower than the two green algal species. Experiments with photosystem
      inhibitors, uncouplers, gamma-radiation, light deprivation, and extended range
      uptake all point to an active transport mechanism for MeHgCl.

PMID- 12214649
TI  - Fluorescent whitening agents in Tokyo Bay and adjacent rivers: their application
      as anthropogenic molecular markers in coastal environments.
AB  - Two kinds of stilbene-type fluorescent whitening agents (i.e., DSBP and DAS1),
      minor components of laundry detergents, were analyzed in surface waters of Tokyo
      Bay and adjacent rivers and in sewage effluents to examine their usefulness as
      molecular markers in the marine environment. Sensitive determination using HPLC
      (high performance liquid chromatography) with fluorescence detection with
      postcolumn UV radiator was employed. DSBP and DAS1 were found in Tokyo rivers at
      concentrations of a few microg/L and approximately 1 microg/L, respectively. DSBP
      and DAS1 were widely distributed in Tokyo Bay waters at concentrations in the
      range of 0.019-0.264 microg/L and 0.021-0.127 microg/L, respectively. Comparison
      of these concentrations with those in sewage effluents (DSBP: 8 microg/L and
      DAS1: 2.5 microg/L on average) yielded sewage dilutions in Tokyo Bay on the order
      of 10(2). FWAs-salinity diagram in the Tamagawa Estuary showed fairly
      conservative behaviors of the FWAs with approximately 20% and approximately 10%
      removal of DSBP and DAS1, respectively. This is thought to be caused by
      photodegradation. The persistent nature of FWAs and their widespread distribution
      in coastal environments demonstrates the utility of FWAs in tracing the behavior
      of water from rivers and sewage outfalls. The DSBP/DAS1 ratio showed a decreasing
      trend from sewage effluents, to rivers, to Tokyo Bay, indicating selective
      photodegradation of DSBP. The DSBP/DAS1 ratio is proposed as an index of the
      degree of photodegradation and residence time and freshness of water mass in
      coastal environments.

PMID- 12214650
TI  - Binding of mercury(II) to dissolved organic matter: the role of the mercury-to
      DOM concentration ratio.
AB  - The binding of Hg(II) to dissolved organic matter (DOM; hydrophobic acids
      isolated from the Florida Everglades by XAD-8 resin) was measured at a wide range
      of Hg-to-DOM concentration ratios using an equilibrium dialysis ligand exchange
      method. Conditional distribution coefficients (K(DOM)') determined by this method
      were strongly affected by the Hg/DOM concentration ratio. At Hg/DOM ratios below
      approximately 1 microg of Hg/mg of DOM, we observed very strong interactions
      (K(DOM)' = 10(23.2+/-1.0) L kg(-1) at pH = 7.0 and I = 0.1), indicative of
      mercury-thiol bonds. Hg/DOM ratios above approximately 10 microg of Hg/mg of DOM,
      as used in most studies that have determined Hg-DOM binding constants, gave much
      lower K(DOM)' values (10(10.7+/-1.0) L kg(-1) at pH = 4.9-5.6 and I = 0.1),
      consistent with Hg binding mainly to oxygen functional groups. These results
      suggest that the binding of Hg to DOM under natural conditions (very low Hg/DOM
      ratios) is controlled by a small fraction of DOM molecules containing a reactive
      thiol functional group. Therefore, Hg/DOM distribution coefficients used for
      modeling the biogeochemical behavior of Hg in natural systems need to be
      determined at low Hg/DOM ratios.

PMID- 12214651
TI  - Fouling of microfiltration and ultrafiltration membranes by natural waters.
AB  - Membrane filtration (microfiltration and ultrafiltration) has become an accepted
      process for drinking water treatment, but membrane fouling remains a significant
      problem. The objective of this study was to systematically investigate the
      mechanisms and components in natural waters that contribute to fouling. Natural
      waters from five sources were filtered in a benchtop filtration system. A
      sequential filtration process was used in most experiments. The first filtration
      steps removed specific components from the water, and the latter filtration steps
      investigated membrane fouling by the remaining components. Particulate matter
      (larger than 0.45 microm) was relatively unimportant in fouling as compared to
      dissolved matter. Very small colloids, ranging from about 3-20 nm in diameter,
      appeared to be important membrane foulants based on this experimental protocol.
      The colloidal foulants included both inorganic and organic matter, but the
      greatest fraction of material was organic. When the colloidal fraction of
      material was removed, the remaining dissolved organic matter (DOM), which was
      smaller than about 3 nm and included about 85-90% of the total DOM, caused very
      little fouling. Thus, although other studies have identified DOM as a major
      foulant during filtration of natural waters, this work shows that a small
      fraction of DOM may be responsible for fouling. Adsorption was demonstrated to be
      an important mechanism for fouling by colloids.

PMID- 12214652
TI  - Exposure chamber measurements of mass transfer and partitioning at the plant/air
      interface.
AB  - Dynamic measures of air and vegetation concentrations in an exposure chamber and
      a two-box mass balance model are used to quantify factors that control the rate
      and extent of chemical partitioning between vegetation and the atmosphere. A
      continuous stirred flow-through exposure chamber was used to investigate the gas
      phase transfer of pollutants between air and plants. A probabilistic two
      compartment mass balance model of plant/air exchange within the exposure chamber
      was developed and used with measured concentrations from the chamber to
      simultaneously evaluate partitioning (Kpa), overall mass transfer across the
      plant/air interface (Upa), and loss rates in the atmosphere (Ra) and aboveground
      vegetation (Rp). The approach is demonstrated using mature Capsicum annuum (bell
      pepper) plants exposed to phenanthrene (PH), anthracene (AN), fluoranthene (FL)
      and pyrene (PY). Measured values of log Kpa (V[air]/V[fresh plant]) were 5.7,
      5.7, 6.0, and 6.2 for PH, AN, FL, and PY, respectively. Values of Upa (m d(-1))
      under the conditions of this study ranged from 42 for PH to 119 for FL. After
      correcting for wall effects, the estimated reaction half-lives in air were 3, 9,
      and 25 h for AN, FL and PY. Reaction half-lives in the plant compartment were 17,
      6, 17, and 5 d for PH, AN, FL, and PY, respectively. The combined use of exposure
      chamber measurements and models provides a robust tool for simultaneously
      measuring several different transfer factors that are important for modeling the
      uptake of pollutants into vegetation.

PMID- 12214653
TI  - Contribution of biogenic emissions to the formation of ozone and particulate
      matter in the eastern United States.
AB  - As anthropogenic emissions of ozone (O3) precursors, fine particulate matter
      (PM2.5), and PM2.5 precursors continue to decrease in the United States, the
      fraction of O3 and PM2.5 attributable to natural sources may become significant
      in some locations, reducing the efficacy that can be expected from future
      controls of anthropogenic sources. Modeling studies were conducted to estimate
      the contribution of biogenic emissions to the formation of O3 and PM2.5 in
      Nashville/TN and the northeastern United States. Two approaches were used to
      bound the estimates. In an anthropogenic simulation, biogenic emissions and their
      influence at the domain boundaries were eliminated. Contributions of biogenic
      compounds to the simulated concentrations of O3 and PM2.5 were determined by the
      deviation of the concentrations in the anthropogenic case from those in the base
      case. A biogenic simulation was used to assess the amounts of O3 and PM2.5
      produced in an environment free from anthropogenic influences in emissions and
      boundary conditions. In both locations, the contribution of biogenic emissions to
      O3 was small (<23%) on a domain-wide basis, despite significant biogenic volatile
      organic compounds (VOC) emissions (65-89% of total VOC emissions). However, the
      production of O3 was much more sensitive to biogenic emissions in urban areas (22
      34%). Therefore, the effects of biogenic emissions on O3 manifested mostly via
      their interaction with anthropogenic emissions of NOx. In the anthropogenic
      simulations, the average contribution of biogenic and natural sources to PM2.5
      was estimated at 9% in Nashville/TN and 12% in the northeast domain. Because of
      the long atmospheric lifetimes of PM2.5, the contribution of biogenic/natural
      PM2.5 from the boundary conditions was higher than the contribution of biogenic
      aerosols produced within the domain. The elimination of biogenic emissions also
      affected the chemistry of other secondary PM2.5 components. Very little PM2.5 was
      formed in the biogenic simulations.

PMID- 12214654
TI  - Enhanced perchloroethylene reduction in column systems using surfactant-modified
      zeolite/zero-valent iron pellets.
AB  - Surfactant- (hexadecyltrimethylammonium, HDTMA) modified zeolite (SMZ)/zero
      valent iron (ZVI) pellets having high hydraulic conductivity (9.7 cm s(-1)), high
      surface area (28.2 m2 g(-1)), and excellent mechanical strength were developed.
      Laboratory column experiments were conducted to evaluate the performance of the
      pellets for perchloroethylene (PCE) sorption/reduction under dynamic flow-through
      conditions. PCE reduction rates with the surfactant-modified pellets (SMZ/ZVI)
      were three times higher than the reduction rates with the unmodified pellets
      (zeolite/ZVI). We speculate that enhanced sorption of PCE directly onto iron
      surface by iron-bound HDTMA and/or an increased local PCE concentration in the
      vicinity of iron surface due to sorption of PCE by SMZ contributed to the
      enhanced PCE reduction by the SMZ/ZVI pellets. Trichloroethylene and cis
      dichloroethylene production during PCE reduction increased with the surfactant
      modified pellets, indicating that the surfactant modification may have favored
      hydrogenolysis over beta-elimination. PCE reduction rate constants increased as
      the travel velocity increased from 0.5 to 1.9 m d(-1), suggesting that the
      reduction of PCE in the column systems was mass transfer limited.

PMID- 12214656
TI  - Removal of cadmium and zinc from aqueous solutions using red mud.
AB  - Red mud, an aluminum industry waste, has been converted into an inexpensive and
      efficient adsorbent. The product obtained has been characterized and utilized in
      batch and column operations for the removal of cadmium and zinc from aqueous
      solutions over a wide range of initial metal ion concentrations (1.78 x 10(-5) to
      1.78 x 10(-3) M for Cd2+ and 3.06 x 10(-5) to 3.06 x 10(-3) M for Zn2+; contact
      time, 24 h) adsorbent dose (5-20 g/L), and pH (1.0-6.0). The removal of Cd2+ and
      Zn2+ was almost complete at low concentrations, while it was 60-65% at higher
      concentrations at optimum pH's of 4.0 and 5.0, respectively, with 10 g/L of
      adsorbent in an 8-10 h equilibration time. The adsorption decreased with increase
      in temperature. Kinetic studies have been used to describe the mechanism of
      adsorption. Chemical regeneration of the columns has been achieved with 1% HNO3.

PMID- 12214655
TI  - Formation and identification of intermediates in the visible-light-assisted
      photodegradation of sulforhodamine-B dye in aqueous TiO2 dispersion.
AB  - The photodegradation of dye pollutants under visible light irradiation in TiO2
      dispersions continues to draw considerable attention because of the greater
      effective utilization of solar energy and its potential application in treating
      wastewaters from textile and photographic industries. To get a better handle on
      the mechanistics details of this TiO2-assisted photodegradation of dyes with
      visible radiation, the process was examined by UV-visible spectroscopy, high
      performance liquid chromatography, silica gel thin-layer chromatography, and
      matrix-assisted laser desorption ionization time-of-flight mass spectrometric
      techniques to separate and identify the N-de-ethylated intermediate products
      during the photodegradation of N,N,N,N-tetraethylsulforhodamine-B (SRB) in the
      absence and presence of iodide ions. Five intermediates, namely, N,N-diethyl-N'
      ethyl-sulforhodamine, N,N-diethylsulforhodamine, N-ethyl-N'-ethylsulforhodamine,
      N-ethylsulforhodamine, and sulforhodamine were thus identified. They correspond
      to intermediate products having a different number of N-ethyl groups, which are
      removed sequentially from the SRB molecule. The reaction process was accompanied
      by the oxidation of I- to I3- in the presence of I- ions. Formation of radicals
      was assessed by spin-trap electron spin resonance spectrometry. The experimental
      results provided the basis for a more detailed description of the reaction
      mechanism(s).

PMID- 12214657
TI  - TiO2-based photocatalytic degradation of 2-chlorophenol adsorbed on hydrophobic
      clay.
AB  - The combination of adsorption and heterogeneous photocatalysis has been
      investigated as a promising technology for the removal of organic water
      pollutants. A laboratory study of the removal and decomposition of 2-chlorophenol
      (2-CP) as a toxic organic pollutant was carried out under various conditions with
      an organophilized clay mineral (hexadecylpyridinium chloride-modified
      montmorillonite; HDPM) as adsorbent and Degussa P25 TiO2 as photocatalyst. Three
      different oxidation processes leading to the degradation of 2-CP were compared:
      direct photolysis, heterogeneous photocatalysis in a TiO2 suspension, and the
      decomposition of substrate adsorbed on HDPM in the presence of TiO2. Both the
      degradation of 2-CP and the formation of intermediates were analyzed by HPLC, the
      total organic carbon content and the total organic and inorganic chloride
      contents were measured to monitor the mineralization process, and X-ray
      diffraction and thermoanalytical measurements were made to characterize the
      hydrophobic clay adsorbent. The heterogeneous photocatalytic degradation of
      dissolved (2-CP/UV/TiO2) and desorbed 2-CP (2-CP/HDPM/UV/TiO2) appeared to be
      equally efficient, whereas direct photolysis of 2-CP was far less efficient in
      the oxidative destruction. HDPM proved to be a suitable adsorbent, capable of
      adsorbing toxic organics from water. It was demonstrated that the adsorbent (at
      relatively high concentration) did not decrease the rate of mineralization of 2
      CP. The results confirmed that the adsorbent retains its structure and
      composition during the mineralization process, and thus it can be reused without
      regeneration. The combination of adsorption and heterogeneous photocatalysis
      studied may be an efficient and economical means of accumulating, removing, and
      oxidizing organic water contaminants, and its application is in accordance with
      the growing environmental demands.

PMID- 12214658
TI  - Distributed reactivity model for sorption by soils and sediments. 15. High
      concentration co-contaminant effects on phenanthrene sorption and desorption.
AB  - Soil and sediment materials having organic matter matrixes of different
      geochemical character were examined with respect to their sorption and desorption
      of phenanthrene in the presence of order-of-magnitude larger concentrations of
      trichloroethylene (TCE) and dichlorobenzene (DCB). These co-contaminants
      depressed phenanthrene sorption in the lowest residual solution phase
      concentration ranges of that target solute investigated, whereas in its highest
      residual concentration regions phenanthrene sorption was either not affected or
      was actually enhanced. In both concentration ranges, the effects observed varied
      with the hydrophobicity and relative concentration of the co-contaminant and with
      the geological maturity and associated degree of condensation and aromatization
      of the soil/sediment organic matter (SOM). Desorption isotherms for phenanthrene
      indicate the occurrence of increased hysteresis in the presence of high
      concentrations of DCB and TCE, the effect increasing with increased degree of
      associated organic condensation. Tests in which high concentrations of DCB and
      TCE were added after completion of the phenanthrene desorption experiments show
      clear evidence of partial displacement of sorbed phenanthrene to the solution
      phase. The results of the work support the concept of SOM glass-transition
      concentrations, above which matrix deformation occurs and so-called "conditioning
      effects" are observed.

PMID- 12214659
TI  - Development, operation, and long-term performance of a full-scale biocurtain
      utilizing bioaugmentation.
AB  - A full-scale field evaluation of bioaugmentation was conducted in a carbon
      tetrachloride (CT)- and nitrate-impacted aquifer at Schoolcraft, MI. The added
      organism was Pseudomonas stutzeri KC (strain KC), a denitrifying bacterium that
      cometabolically degrades CT without producing chloroform (CF). To introduce and
      maintain strain KC in the aquifer, a row of closely spaced (1-m)
      injection/extraction wells were installed normal to the direction of groundwater
      flow near the leading edge of the CT plume. The resulting system of wells was
      used to establish and maintain a "biocurtain" for CT degradation through the
      intermittent addition of base to create favorable pH conditions; inoculation; and
      weekly addition of acetate (electron donor), alkali, and phosphorus. Although
      half of the test zone was inoculated twice, the long-term performance of both
      sections was indistinguishable: both had high CT removal efficiencies (median of
      98-99.9%) and similar levels of strain KC colonization (>10(5) strain KC/g).
      Sustained and efficient (98%) removal of CT has now been observed over 4 yr.
      Transient low levels of CF (<20 ppb) and H2S (<2 ppm) were observed, but both
      disappeared when the concentration of acetate in the weekly feed was reduced.
      Nitrate removal efficiencies ranged from 60% at low acetate concentrations to
      nearly 100% at high acetate concentrations. We conclude that closely spaced wells
      and intermittent substrate addition are effective means of delivering organisms
      and substrates to subsurface environments. At the Schoolcraft site, we achieved
      uniform removal efficiencies over a significant vertical depth (15 m), despite
      significant variability in hydraulic conductivity. This was accomplished by
      pumping 65% (v/v) of the natural gradient flow passing through the biocurtain
      during a given week in a single 6-h pumping event. Approximately 18,600 m3 of
      contaminated groundwater was treated during the project.

PMID- 12214660
TI  - N-oxidative transformation of free and N-substituted amine functions by
      cytochrome P450 as means of bioactivation and detoxication.
AB  - Indirect evidence for the participation of cytochrome P450 (P450) in the
      microsomal N-oxygenation of primary and N-substituted amine functions is
      presented by studies employing diagnostic modifiers of the hemoprotein system as
      well as immunochemical approaches. Experiments with recombinant hemoproteins or
      isozymes purified from the tissues of various animal species support the results
      obtained by the inhibitor assays. Amine substrates and the redox proteins of the
      microsomal electron transfer chain reveal to be mutually beneficial in
      interactions with P450s. Numerous N-substituted amines undergo P450-catalyzed N
      oxidative transformation despite the presence of accessible alpha-C hydrogens in
      these structures rather thought to favor N-dealkylation. In these instances,
      stabilization of the initially formed aminium radicals by the specific active
      site orientation of the particular P450s obviously permits oxygen rebound. Apart
      from common iron-oxenoid chemistry involving a (FeO)3+ species, iron-bound
      hydroperoxide, (FeO2H)3+, appears to act as an electrophilic oxidant with certain
      N-substituted amines and P450 subforms. Generally, P450-mediated N-oxygenation of
      amines can produce cytotoxic and mutagenic metabolites, but equally can well
      yield hydrophilic products, that are readily excreted and thus promote
      detoxication.

PMID- 12214661
TI  - Electron supply and catalytic oxidation of nitrogen by cytochrome P450 and nitric
      oxide synthase.
AB  - Cytochrome P450 and nitric oxide synthase (NOS) oxidize nitrogen atoms, although
      the substrates and transformations are highly restricted for NOS. The first
      reaction catalyzed by NOS is mediated by a P450-like ferryl species, although it
      is generated by a distinct process in which a tetrahydrobiopterin molecule in NOS
      serves as a transient electron donor. The second NOS reaction appears to be
      mediated by an iron dioxygen precursor of the ferryl species. The transient
      tetrahydrobiopterin radical formed in these reactions is quenched by electron
      transfer from the NOS flavin domain. Electron transfer from the flavins is
      controlled by the binding of calmodulin, the presence of peptide inserts in the
      flavin domain, the substrate structure, and phosphorylation of the enzyme.

PMID- 12214662
TI  - An overview of the mechanism, substrate specificities, and structure of FMOs.
AB  - Kinetic studies carried out over the past three decades, primarily with purified
      pig liver flavin-containing monooxygenase (FMO1), demonstrated that the mechanism
      of this flavoenzyme was distinctly different from other widely studied flavin
      dependent monooxygenases in that reduction of O2 by nicotinamide-adenine
      dinucleotide-phosphate reduced (NADPH) occurred before the addition of the
      xenobiotic substrate. Compounds bearing a soft nucleophilic heteroatom show
      substrate activity provided they could contact the enzyme-bound 4a-hydroperoxy
      flavin. Structure-activity studies suggest that in addition to nucleophilicity,
      size and charge of potential substrates are important parameters limiting access
      to the enzyme-bound hydroxylating intermediate form of the enzyme. The mechanism
      of FMO 1, 2, 3, and 4 are similar and differences in the substrate specificities
      of these isoforms can be attributed almost entirely to differences in the
      dimensions of the cleft or channel limiting access to the 4a-hydroperoxy flavin.
      While this model provides a satisfactory mechanism for the FMO catalyzed
      oxidation of very soft nucleophiles, it does not address another very important
      element of the catalytic cycle. The amine nitrogen atom is not an especially soft
      nucleophile readily hydroxylated by peroxides or peracids. How the enzymes
      convert an amine substrate to a form readily attacked by the hydroperoxy flavin
      is presently unknown. A complete resolution of this problem will only be possible
      after the tertiary structures of these enzymes are solved.

PMID- 12214663
TI  - Human and plant flavin-containing monooxygenase N-oxygenation of amines:
      detoxication vs. bioactivation.
AB  - Generally, the flavin-containing monooxygenase of mammalian systems has been
      considered a detoxication enzyme converting nucleophilic heteroatom-containing
      chemicals into polar, more readily excreted metabolites. The beneficial effects
      of this process are thought to be participation in the detoxication of foodstuffs
      and other xenobiotics that might otherwise be bioactivated by other enzyme
      systems. The physiological role of mammalian FMO is unknown although it has been
      observed that many heteroatom-containing chemicals in plants are efficiently
      oxygenated by FMO. Recently, a plant FMO-like enzyme has been characterized and
      it appears to possess many of the same functional properties of mammalian FMO.
      The advantage of studying the FMO-like genes and enzymes in Arabidopsis as a
      model system allows for the investigation of the role of FMO-like enzymes in
      plant growth and development. The Arabidopsis FMO-like gene product, while
      resembling the mammalian counterpart in many respects, is quite distinct.
      However, study of the Arabidopsis FMO-like enzyme may provide considerable
      insight into the possible role of mammalian FMOs in biogenic amine metabolism.

PMID- 12214664
TI  - Genetic polymorphisms of flavin-containing monooxygenase (FMO).
AB  - Mammalian flavin-containing monooxygenase (FMO) exists as six gene families and
      metabolizes a plethora of drugs and xenobiotics. The major FMO in adult human
      liver, FMO3, is responsible for trimethylamine (TMA) N-oxygenation. A number of
      FMO3 mutant alleles have been described and associated with a disease termed
      trimethylaminuria (TMAU). The TMAU patient excretes large amounts of TMA in urine
      and sweat. A more recent ethnically related polymorphism in expression of the
      major FMO in lung, FMO2, has been described. All Caucasians and Asians genotyped
      to date are homozygous for a CAG --> TAG amber mutation resulting in a premature
      stop codon and a nonfunctional protein truncated at AA 472 (wildtype FMO2 is 535
      AA). This allele has been designated hFMO2*2A. Twenty-six percent of individuals
      of African descent and 5% of Hispanics genotyped to date carry at least one
      allele coding for full-length FMO2 (hFMO2*1 allele). Preliminary evidence
      indicates that FMO2.1 is very active toward the S-oxygenation of low MW
      thioureas, including the lung toxicant ethylene thiourea. Polymorphic expression
      of functional FMO2 in the individuals of African and Hispanic descent may
      markedly influence drug metabolism and/or xenobiotic toxicity in the lung.

PMID- 12214665
TI  - Studies on the oxidation of 1,4-disubstituted-1,2,3,6-tetrahydropyridines.
AB  - Interest in the parkinsonian-inducing proneurotoxin 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine has prompted extensive studies into the oxidative pathways
      mediating its bioactivation to the corresponding pyridinium species, a potent
      inhibitor of the mitochondrial electron transport chain. The initial step in the
      overall reaction is the two-electron ring alpha-carbon oxidation to give the 1
      methyl-4-phenyl-2,3-dihydropyridinium species, a reaction that is catalyzed by
      monoamine oxidase B. The same a-carbon oxidation is catalyzed by members of the
      cytochrome P-450 family of oxidases. This paper examines the impact that various
      structural features of 1,4-disubstituted-1,2,3,6-tetrahydropyridinyl derivatives
      have on the oxidative fate of this class of compound.

PMID- 12214666
TI  - N-oxidation of aromatic amines by intracellular oxidases.
AB  - The introduction includes a literature review of DNA reactive species and DNA
      adduct formation that results from aromatic amine N-oxidation catalyzed by
      hepatic cytochrome P450 vs. that catalyzed by nonhepatic peroxidases.
      Experimental evidence is then described for a novel oxidative stress mechanism
      involving prooxidant N-cation radical formation by both oxidases, which is
      proposed as a contributing mechanism for aromatic amine induced cytotoxicity and
      carcinogenesis. Aromatic amine N-cation radicals formed by peroxidases were found
      to cooxidize GSH or NADH and form reactive oxygen species. The latter could
      explain the reported DNA oxidative damage found in vivo following
      methylaminoazobenzene administration [Hirano et al. Analyses of Oxidative DNA
      Damage and Its Repair Activity in the Livers of 3'-Methyl-4
      dimethylaminoazobenzene-Treated Rodents. Jpn. J. Cancer Res. 2000, 91, 681-685].
      It was also found that the prooxidant activity of the aromatic amine increased as
      its redox potential, i.e., ease of oxidation decreased with o-anisidine and
      aminofluorene being the most effective at forming reactive oxygen species. This
      suggests that the rate-limiting step in the cooxidation is the rate of arylamine
      oxidation by the peroxidase. Incubation of hepatocytes with aromatic amines
      caused a decrease in the mitochondrial membrane potential before cytotoxicity
      ensued. The CYP1A2-induced hepatocytes isolated from 3-methylcholanthrene
      administered rats were much more susceptible to some arylamines and were
      protected by CYP1A2 inhibitors. Hepatocyte GSH was also depleted by all
      arylamines tested and extensive GSH oxidation occurred with o-anisidine and
      aminofluorene, which was prevented by CYP1A2 inhibitors. This suggests that in
      intact hepatocytes CYP1A2 may also catalyze a one-electron oxidation of some
      arylamines to form prooxidant cation radicals, which cooxidize GSH to form the
      reactive oxygen species.

PMID- 12214667
TI  - Reduction of N-hydroxylated compounds: amidoximes (N-hydroxyamidines) as pro
      drugs of amidines.
AB  - In order to examine the importance of metabolic cycles and in particular of
      reductions of N-hydroxylated compounds, the reversible metabolism at the amidine,
      guanidine, and amidinohydrazone nitrogen atoms of various drugs and model
      compounds was investigated. Many of these N-oxygenated metabolites are very
      easily reduced back into the starting materials. A comparison of the kinetic data
      for the N-hydroxylation and reduction suggests that the reduction should
      predominate in vivo. This could be verified by in vivo studies. Thus, N
      hydroxylated amidines (amidoximes) can be used as pro-drugs of amidines. Because
      of their strong basicity, amidines, guanidines, and amidinohydrazones are
      protonated under physiological conditions, are very hydrophilic, and are usually
      not absorbed from the gastrointestinal tract. The N-hydroxylated derivatives of
      amidines (amidoximes), guanidines (N-hydroxyamidines), and amidinohydrazones (N
      hydroxyamidinohydrazones) are less basic because of the introduction of the
      oxygen atom. They are absorbed from the gastrointestinal tract and then reduced
      to the active amidines, guanidines, and amidinohydrazones. The pro-drug principle
      was originally developed in our laboratory for pentamidine and then applied to
      other amidines such as sibrafiban and melagatran (ximelagatran). The enzymatic
      basis of N-oxidative processes is very well understood, whereas reductions have
      been less extensively investigated. We purified an enzyme system from pig and
      human liver consisting of cytochrome b5, its reductase, and a P450 enzyme, which
      is involved in the reduction of the N-hydroxylated compounds. Similar activities
      were found in all species studied so far. Furthermore, comparable reductive
      reactions could also be demonstrated with microsomal fractions from organs other
      than liver. In addition, mitochondria are highly capable of performing the
      reductions of these N-hydroxylated compounds. Thus, several organs and cell
      organelles are involved in the reduction explaining the extensive reduction of
      the pro-drugs in vivo underlying the suitability of the concept for drug
      development.

PMID- 12214668
TI  - Bioreductively activated antitumor N-oxides: the case of AQ4N, a unique approach
      to hypoxia-activated cancer chemotherapy.
AB  - Aliphatic amine N-oxides have long been identified as non-toxic metabolites of a
      large number of tertiary amines drugs. Bioreduction of such N-oxides will
      generate the active parent amine. This principle has been adopted to develop
      AQ4N, a di-N-oxide anticancer prodrug with little intrinsic cytotoxicity.
      However, AQ4N is bioreduced in hypoxic regions of solid tumors and
      micrometastatic deposits to generate a cytotoxic alkylaminoanthraquinone
      metabolite. The 4-electron reduction metabolite of AQ4N has high affinity for DNA
      and is a potent inhibitor of topoisomerase II, a DNA processing enzyme crucial to
      cell division. The development of AQ4N has proceeded on many fronts in order to
      establish this unique anticancer prodrug opportunity. Preclinical studies in vivo
      have demonstrated that although AQ4N has little or no intrinsic cytotoxic
      activity per se it (i) enhances the antitumor effects of radiation and
      conventional chemotherapeutic agents, (ii) is pharmacokinetically stable, and
      (iii) is a substrate for cytochrome P450 (CYP). A study of AQ4N metabolism in
      vitro and ex vivo using purified CYP enzymes, phenotyped human livers and CYP
      transfected cell lines shows that CYP3A, 1A and 1B1 family members contribute to
      AQ4N bioreduction in the absence of oxygen. Importantly AQ4N is shown to be
      metabolized by tumors known to express CYP isoforms. AQ4N is currently in Phase I
      clinical trials.

PMID- 12214669
TI  - Oxidation of N-hydroxyguanidines by cytochromes P450 and NO-synthases and
      formation of nitric oxide.
AB  - Microsomal cytochromes P450 and tetrahydrobiopterin (BH4) free-NOS II catalyze
      the oxidation of N-hydroxyguanidines by NADPH and O2 with formation of nitrogen
      oxides including NO. These reactions are not selective in terms of substrates, as
      they occur on most N-hydroxyguanidines, and of products, as they not only lead to
      corresponding ureas but also to cyanamides. These non selective reactions are
      mainly due to O2- derived from the oxidase function of those hemeproteins. By
      contrast, NO synthase (NOS) containing BH4 catalyze the selective monooxygenation
      of some N-hydroxyguanidines by NADPH and O2 with formation of NO and the
      corresponding ureas in a 1:1 molar ratio. Those reactions are not inhibited by
      superoxide dismutase (SOD) and are performed by the NOS Fe(II)-O2 complex. The
      endogenous NOS substrate N(omega)-hydroxy-L-arginine (NOHA), and its close
      analogue homo-NOHA, are selectively oxidized in this manner by NOS whereas nor
      NOHA and dinor-NOHA are not. Moreover, some non alpha-amino acid N
      hydroxyguanidines act as NOS substrates in a manner similar to NOHA. This
      includes a small number of simple N-alkyl N'-hydroxyguanidines with R(alkyl)
      propyl, butyl, and pentyl, and some N-aryl N'-hydroxyguanidines that involve a
      relatively small and preferably electron-rich aryl substituent. The best
      exogenous substrate of NOS reported so far is N-butyl N'-hydroxyguanidine; this
      compound is oxidized by NOS II with formation of NO with a catalytic efficiency
      (kcat/Km) only two times lower than NOHA itself. N-butyl N'-hydroxyguanidine is
      also a good substrate for NOS I and NOS III. However, some N-aryl N'
      hydroxyguanidines, with Ar = p-chlorophenyl and p-methylphenyl, are selective
      substrates of NOS II. These results show that exogenous N-hydroxyguanidines not
      bearing an alpha-amino acid function are efficiently and selectively oxidized by
      NOS with forrmation of NO. They open the way toward the research of new NO donors
      based on selective substrates of each class of NOS.

PMID- 12214670
TI  - N-hydroxyarylamines.
AB  - Aryl and heterocyclic amines are of particular interest because of their
      carcinogenicity. The N-hydroxy derivatives are formed by oxidation, usually by
      the cytochrome P450 (P450) enzymes and most often by P450 family 1. The mechanism
      of oxidation appears to resemble that of other P450 reactions. The N-hydroxy
      products can be conjugated to yield esters, which are unstable and form nitrenium
      ions. Reaction with DNA is most common at the N2 atom and particularly at the C8
      atom of guanine. A mechanism involving initial formation of an N7-guanyl adduct
      can be utilized in explaining the C 8-guanyl adducts plus several other side
      reactions. The high mutagenicity of N-hydroxy heterocyclic amines in bacterial
      systems has provided a useful tool for the development of models useful for
      screening and chemoprevention and for the generation of P450 enzymes with altered
      properties.

PMID- 12214671
TI  - Heterocyclic aromatic amine metabolism, DNA adduct formation, mutagenesis, and
      carcinogenesis.
AB  - Heterocyclic aromatic amines (HAAs) are carcinogenic compounds formed in meats,
      fish, and poultry prepared under common household cooking practices. Some HAAs
      are also formed in tobacco smoke condensate. Because of the widespread occurrence
      of HAAs in these daily staples, health concerns have been raised regarding the
      potential role of HAAs in the etiology of some human cancers associated with
      frequent consumption of these products. In this review, the metabolism of HAAs to
      biologically active metabolites that bind to DNA and provoke mutations and cancer
      in various biological systems is discussed. Some of the current analytical and
      molecular methods that are used to measure biomarkers of HAA exposure and genetic
      damage in experimental animal models and humans are also presented. These
      biochemical data combined may help to better assess the role that HAAs may have
      in the development of some common forms of human cancers.

PMID- 12214672
TI  - N-oxidation of drugs associated with idiosyncratic drug reactions.
AB  - Circumstantial evidence strongly suggests that most idiosyncratic drug reactions
      are due to reactive metabolites of drugs rather than due to the drugs themselves.
      Many of the drugs that are associated with idiosyncratic drug reactions contain
      nitrogen. There are many possible reasons for this association. One is simply
      that many drugs, especially CNS active drugs, contain nitrogen. In addition,
      nitrogen is relatively easy to oxidize because of its lone pair of electrons and
      many nitrogen-containing compounds readily undergo redox cycling, which can
      generate reactive oxygen species. There are several nitrogen-containing function
      groups that are especially associated with adverse reactions. These include
      aromatic amines, nitro compounds (nitro compounds are reduced to the same
      reactive intermediates as are formed by oxidation of the corresponding aromatic
      amine), hydrazines and compounds that can be oxidized to iminoquinone and related
      compounds. A greater attention to the issue of reactive metabolites during drug
      development would likely lead to safer drugs; however, not all drugs that form
      reactive metabolites are associated with a high incidence of idiosyncratic drug
      reactions. In addition to the presence of such a group, other factors, such as
      dose and electron density of the compound, appear to play a role in whether the
      drug containing such functional groups will be associated with a relatively high
      incidence of idiosyncratic drug reactions.

PMID- 12214673
TI  - Role of human cytochrome P450 (CYP) in the metabolic activation of nitrosamine
      derivatives: application of genetically engineered Salmonella expressing human
      CYP.
AB  - The role of human cytochrome P450 (CYP) in the metabolic activation of tobacco
      related N-nitrosamines was examined by Salmonella mutation test using a series of
      genetically engineered Salmonella typhimurium YG7108 strains each co-expressing a
      form of CYP (CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6,
      CYP2E1, CYP3A4, and CYP3A5) together with human NADPH-cytochrome P450 reductase.
      Seven tobacco-related N-nitrosamines such as 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanone, N-nitrosodiethylamine, N-nitrosopyrrolidine, N-nitrosopiperidine, N
      nitrosonornicotine, N-nitrosoanabasine, and N-nitrosoanatabine were used. The
      CYP2A6 was found to be responsible for the mutagenic activation of essentially
      all tobacco-related N-nitrosamines examined. On the basis of the evidence,
      genetic polymorphism of the CYP2A6 gene appeared to be one of the factors
      determining cancer susceptibility caused by smoking. Previously, we found the
      whole deletion of the CYP2A6 gene (CYP2A6*4C) as a type of genetic polymorphism
      in Japanese. We hypothesized that individuals possessing the gene homozygous for
      CYP2A6*4C were incapable of activating tobacco-related N-nitrosamines and showed
      lower susceptibility to lung cancer induced by tobacco smoke. Thus, the
      relationship between the CYP2A6*4C and the susceptibility to the lung cancer was
      evaluated. The frequency of the CYP2A6*4C was significantly lower in the lung
      cancer patients than healthy volunteers, suggesting that the subjects carrying
      the CYP2A6*4C alleles are resistant to carcinogenesis caused by N-nitrosamines
      because of the poor metabolic activation capacity. Taking these results into
      account, CYP2A6 is an enzyme enhancing lung cancer risk.

PMID- 12214674
TI  - Leveling the playing field? Exploring the merits of the ethics-as-process
      approach for judging qualitative research proposals.
AB  - There has been a recent growth in claims that qualitative research proposals are
      not treated equitably by ethics committees. In response, recent arguments
      centered on establishing the ethics of qualitative research, in the eyes of
      ethics committees, have indicated the need for an "ethics-as-process" approach.
      Accordingly, in this article, the authors illustrate the merits of this approach
      and provide three examples from the field: the outcomes of participating in
      qualitative interviews, sensitive handling of ending in qualitative research
      relationships, and the ongoing establishment of informed consent. The authors
      hope to increase awareness of the potential benefits of this approach and
      contribute to the ensuing debate.

PMID- 12214675
TI  - Intuitive inquiry.

PMID- 12214676
TI  - Informal networks among women with HIV/AIDS: present support and future
      prospects.
AB  - Given the importance of informal support in the lives of chronically ill people,
      it is imperative to gain a deeper understanding of the nature and impact of HIV
      positive women's informal networks. Through interviews with 37 women with HIV
      infection, the author explores women's social network composition and the extent
      to which these networks appear to facilitate or mediate the disruption caused by
      HIV/AIDS. Women reported having at least one person, usually a family member, on
      whom they could depend for emotional support. Although women report adequate
      levels of current support, the author questions the likelihood that their
      informal networks will provide support further along in women's illness
      trajectories.

PMID- 12214677
TI  - Constructing compatibility: managing breast-feeding and weaning from the mother's
      perspective.
AB  - The purpose of this grounded theory study was to analyze the maternal process of
      managing the later stages of established breast-feeding and, ultimately, weaning
      the child from the breast within a Western Australian context. Data were analyzed
      from 33 participants' interview transcripts, field notes, 9 postal questionnaires
      from fathers, and individual and discussion group interviews with child health
      nurses. A common social problem of incompatible expectations was revealed. All
      participants faced a dilemma in the management of their experience when personal
      expectations were in opposition to others' expectations. A process of
      Constructing Compatibility by Adapting Focus was adopted to compensate for this
      incompatibility.

PMID- 12214678
TI  - Understanding conflicts between health professionals: a narrative approach.
AB  - This article is an examination of one conflict story out of a total of 101
      conflict stories from a Norwegian urban hospital. The data comes from an
      ethnographic study and was gathered through interviews, observations, and
      existing documents. The author demonstrates how conceptualizing professional
      conflicts as narratives can bring new insights to understanding, explaining, and
      resolving conflicts. A major contribution of the narrative approach to conflict
      management is the emphasis on the conflict as an integral part of the story.
      Conflict management approaches inspired by research from a positivistic tradition
      often look beyond the story to the real issues, treating the stories as
      anecdotes. Within the narrative approach, the parties' stories are considered an
      integral part of the conflict and solution.

PMID- 12214679
TI  - Changes in self-concept while using SSRI antidepressants.
AB  - In this study, the authors analyze how younger women see themselves within the
      context of using the antidepressants selective serotonin re-uptake inhibitors
      (SSRIs). Twelve in-depth interviews and 6 reinterviews were conducted with a
      community-based sample of women who had been taking SSRIs between 1 and 4 years.
      The empirical analysis revealed that SSRI users passed through stages in their
      careers as medicine users, these stages corresponding to how the users thought
      and felt about themselves. Four major changes in self-concept emerged: distressed
      and needing help, conflicts about taking the medicine, improvements in condition,
      and problems discontinuing the medicine. Users evaluated themselves from what
      they believed was the perspective of society, and the way they saw themselves was
      closely related to how they felt they functioned in everyday life.

PMID- 12214680
TI  - A discourse analysis of nursing diagnosis.
AB  - The author presents a discourse analysis in three sections: a genealogy, a
      structural discourse analysis, and a power analytic. She concludes that the
      discourse of nursing diagnosis sustains conditions of social domination, limits
      autonomy and responsibility, and oppresses individuals and groups. The discourse
      of nursing diagnosis restricts what counts as evidence and limits acceptable
      input of voices, thus excluding, for example, the voices of the patient and his
      or herfamily. The discourse of nursing diagnosis appeals to the dominance of
      empirical analytic science and equates this dominance with professional social
      status. The author discusses potential discourses of resistance that provide
      speaking positions from which to articulate specific practices that resist
      oppressive effects of nursing diagnosis.

PMID- 12214681
TI  - Studying health care "quality" qualitatively: the dilemmas and tensions between
      different forms of evaluation research within the U.K. National Health Service.
AB  - The authors tell the story of an attempt to depart from a tradition of evaluation
      research (ER) and to address the research-practice interface in a different way
      through a more hands-on, action research (AR) approach, which combines
      qualitative and quantitative methods. In doing so, they raise issues about the
      role and nature of evaluation for development and, especially, about the place of
      qualitative research in such evaluations; the identity of future ER; "paradigm
      wars" between the positivists and the phenomenologists; and the politics of
      conducting policy-based evaluations in health care settings and of what happens
      when qualitative researchers try to help an improvement process.

PMID- 12214682
TI  - Naturalistic inquiry and reliabilism: a compatible epistemological grounding.
AB  - In this brief analysis, the authors suggest that naturalistic inquiry as a field
      must return to a more rigorous interpretation of epistemological issues. The need
      is highlighted by the fact that ideological and methodological claims are
      increasingly becoming conflated. This produces a distancing of what is truly at
      stake: a need to defend a genuine epistemological theory consistent with the aims
      of naturalistic perspectives and establish some ontological commitments as a
      result. The authors argue that the epistemological theory of process reliabilism
      is worth examining critically. They also suggest its consistency with the
      ontological claims of minimal realism.

PMID- 12214683
TI  - Identifying individual competency in emerging areas of practice: an applied
      approach.
AB  - Competency designation is important for any discipline to define individual
      performance expectations. Although public health (PH) agencies have always
      responded to emergencies, individual expectations have not been specified. The
      authors identified individual competencies necessary for organizations to meet
      performance standards. In the first stage, a Delphi survey served to identify
      competencies needed by staff to respond to any emergency, including bio
      terrorism, yielding competency sets for four levels of workers. In the second
      stage, focus groups were used to assess the competencies with public health
      agencies. This feedback validated the Delphi-identified competencies as accurate
      and necessary for emergency response. The authors demonstrate the feasibility of
      using these methods to arrive at statements of value to PH practice at a
      reasonable investment of resources.

PMID- 12214684
TI  - Copolymer solutions as separation media for DNA capillary electrophoresis.
AB  - A review on copolymers used as DNA separation media in capillary electrophoresis
      is presented. Copolymers can combine the desirable properties of different
      monomers, yielding many attractive features, such as high sieving ability, low
      viscosity, self-assembly behavior and dynamic coating ability. Copolymers with
      different molecular architecture, including block copolymers, random copolymers,
      and graft copolymers, have been developed and tested as DNA separation media with
      unique and tailored properties that cannot be achieved easily by using only
      homopolymers.

PMID- 12214685
TI  - Preparative separation of isomeric sulfophthalic acids by conventional and pH
      zone-refining counter-current chromatography.
AB  - Two modes of high-speed counter-current chromatography (HSCCC) were applied to
      separate 3- and 4-sulfophthalic acid from a mixture. Conventional HSCCC was
      useful for the separation of up to several hundred milligram quantities of these
      positional isomers, while pH-zone-refining CCC was implemented successfully to
      separations at the multigram level. The conventional HSCCC separations were
      performed with a standard J-type HSCCC system that has a superior resolution but
      a lower level of retention of the stationary phase of the biphasic solvent system
      used (acidified n-butanol-water). The pH-zone-refining CCC separations were
      performed with an X-type HSCCC system (a cross-axis system) that has a higher
      capability for retention of the stationary phase. The purified positional isomers
      (over 99% pure as determined by HPLC) were characterized by 1H NMR and negative
      ion electrospray ionization mass spectrometry.

PMID- 12214686
TI  - Screening approach for chiral separation of pharmaceuticals part II. Reversed
      phase liquid chromatography.
AB  - A screening strategy for the rapid separation of drug enantiomers by reversed
      phase liquid chromatography was developed using three cellulose/amylose
      stationary phases. The key point to achieve enantioselectivity is the control of
      the compound ionisation. Only two mobile phases, i.e. an acidic phosphate buffer
      (pH 2.0) containing a chaotropic salt (KPF6) and a borate buffer (pH 9.0) mixed
      with acetonitrile, are used in the proposed strategy. This strategy was
      successfully applied to a set of 37 diverse chiral pharmaceuticals. Satisfactory
      enantioselectivity was achieved for 89% of them.

PMID- 12214687
TI  - Improved performance of gravitational field-flow fractionation for screening wine
      making yeast varieties.
AB  - Performance of gravitational field-flow fractionation (GFFF) is improved here
      with respect to the ability to fractionate and distinguish different varieties of
      wine-making yeast from Saccharomyces cerevisiae. A new GFFF channel with non
      polar walls has been employed to enhance fractionation selectivity and
      reproducibility. Since GFFF retention depends from first principles on particle
      size, Coulter counter measurements were performed in order to compare size
      distribution profiles with GFFF profiles. From such a comparison, GFFF was shown
      to be able to reveal differences in yeast cells other than size. This could make
      use of GFFF for screening different varieties of wine-making yeast towards future
      quality assessment procedures based on a possible correlation between yeast cell
      morphology indexes and quality indexes.

PMID- 12214688
TI  - Contribution to the time balance in gas-liquid chromatography new definition
      equations of the retention times and retention volumes.
AB  - The numerous research groups and researchers, as well as IUPAC, that during the
      last half century have dealt with different theoretical and practical problems in
      gas-liquid chromatography (GLC), including its nomenclature, have failed in
      giving an exact definition equation of the net retention time. Using our earlier
      results and starting from a time balance of GLC we have solved this problem by
      introducing the so-called acceleration time, t(ac), in the absence of which, the
      theoretical plate number concept, including the stationary phase transfer, is
      misinterpreted. The measurements were carried out both on support coated and on
      wall-coated open tubular columns with apolar and polar stationary phases.
      Different relationships of t(ac) with some solute properties and the column
      temperature for a series of n-alkanes on an apolar stationary phase under
      isothermal conditions were tested. The results obtained are presented in
      different tables and mathematical relationships.

PMID- 12214689
TI  - Determination of chlormequat and mepiquat in pear, tomato, and wheat flour using
      on-line solid-phase extraction (Prospekt) coupled with liquid chromatography
      electrospray ionization tandem mass spectrometry.
AB  - A sensitive and selective method is presented for the simultaneous analysis of
      the pesticides chlormequat and mepiquat at trace levels in tomato, pear, and
      wheat flour. The method entails direct injection of the food extract onto an on
      line solid-phase extraction (SPE) instrument (Prospekt) using a strong cation
      exchange resin. Analyte separation and detection is done by liquid chromatography
      electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS). Surrogate
      standards (d9-chlormequat, d6-mepiquat) are employed to compensate for recovery
      losses and potential MS-MS signal suppression. The method achieves a limit of
      quantification for both cationic analytes at or below 5 microg/kg, and good intra
      and inter-assay precision with mean variability values <7% over a concentration
      range up to 195 microg/kg. This study also addresses potential analyte carry-over
      in an SPE on-line system, as well as the robustness of the procedure and its
      applicability in routine quality control operations.

PMID- 12214690
TI  - Matrix-effects of vegetable commodities in electron-capture detection applied to
      pesticide multiresidue analysis.
AB  - The influence of the sample matrix in the analysis of pesticides in vegetable
      samples has been studied in order to determine if the matrix content introduces a
      systematic or proportional (or both) bias in the measurements. Experiments have
      been carried out during a 4-month period, in which calibration curves, prepared
      in solvent and in vegetable matrix, were prepared and analysed. A statistical
      treatment has been applied in order to: (i) check the stability of such
      calibrations during the period studied; (ii) compare both solvent and matrix
      matched calibrations; and (iii) obtain a correction function. Applying the
      correction function to the results obtained with a solvent calibration it is
      possible to make a prediction of the values obtained applying a matrix-matched
      calibration. The performance of the correction function has been validated with
      recovery data. Finally the uncertainty derived from the use of each calibration
      plot and the correction function has been calculated.

PMID- 12214691
TI  - Determination of minor and trace volatile compounds in wine by solid-phase
      extraction and gas chromatography with mass spectrometric detection.
AB  - A new method for the quantitative determination of important wine odorants has
      been developed. The wine (50 ml) is extracted in a 200 mg solid-phase extraction
      (SPE) cartridge filled with Lichrolut-EN resins from Merck. The elution is
      carried out with 1.3 ml of dichloromethane. These extracts are directly analyzed
      by GC-Ion Trap-MS without further concentration. Twenty-seven important wine
      odorants, such as volatile phenols, vanillin derivatives, aliphatic lactones, nor
      isoprenoids, minor esters and terpenols, can be quantitatively determined in a
      single gas chromatography-mass spectrometry (GC-MS) run. The recoveries in the
      SPE isolation are in good agreement with those expected from the calculation of
      breakthrough volumes from solid-liquid distribution coefficients and are higher
      than 90%, except for guaiacol, vanillin, 2,6-dimethoxyphenol and 4-vinylphenol.
      In most cases, precision is below 10%. Method linearity is satisfactory, with r2
      higher than 0.99 in all cases. The analysis of spiked samples has shown that
      there is good agreement between the real mass of compound added to the wine and
      that determined by analysis. In all cases detection limits are below the odor
      detection threshold of the compounds, and the calibrated interval covers the
      natural range of occurrence of the compounds in wine.

PMID- 12214692
TI  - Enantiomeric separations using poly(L-valine) and poly(L-leucine) surfactants.
      Investigation of steric factors near the chiral center.
AB  - This study examined the effect of steric factors near the stereogenic center on
      polymerized surfactants, sodium N-undecyl-L-leucine, sodium N-undecyl-L
      norleucine, sodium N-undecyl-L-tert.-butyl leucine, sodium N-undecyl-L
      isoleucine. sodium N-undecyl-L-valine, sodium N-undecyl-L-norvaline. and sodium N
      undecyl-L-proline. The effect of steric factors near the chiral center of the
      polymeric surfactants were examined using binaphthyl derivatives,
      aminoglutethimide, and 2,2,2-trifluoro-1-(9-anthryl)ethanol. In addition,
      fluorescence spectroscopy was used to determine the hydrophobicities of these
      surfactants using the environmentally-sensitive probe pyrene.

PMID- 12214693
TI  - Capillary electrophoretic enzyme immunoassay with electrochemical detection for
      cortisol.
AB  - A novel capillary electrophoretic enzyme immunoassay with electrochemical
      detection has been developed and used for the determination of cortisol. In this
      method, after the competitive enzyme immunoreaction, the free enzyme (horseradish
      peroxidase, HRP)-labeled cortisol (HRP-cortisol) and the bound enzyme-labeled
      cortisol (HPR-cortisol-anti-cortisol) were separated in the separation capillary
      and then catalyzed the enzyme substrate [3,3,5,5-tetramethyl-benzidine
      dihydrochloride, TMB(Red)] in the reaction capillary. The product of the
      enzymatic catalysis reaction [TMB(Ox)] was amperometrically detected on a carbon
      fiber microdisk bundle electrode. A concentration limit of detection (LOD) of 1.7
      x 10(-1) mol/l, which corresponds to a mass LOD of 7.8 amol, was achieved with
      the relative standard deviation of 3.3%. The method has been verified using the
      cortisol controls.

PMID- 12214694
TI  - Effects of metal ions on concentration of DNA in high-conductivity media by
      capillary electrophoresis.
AB  - On-line concentration and separation of DNA prepared in low- or high-conductivity
      media has been demonstrated using poly(ethylene oxide) (PEO) solution in the
      presence of electroosmotic flow. DNA fragments migrating against EOF stacked at
      the boundary between the sample zone and PEO solutions, mainly because of sieving
      and increases in the viscosity. Unlike conventional methods, the large DNA
      fragments were detected earlier toward the cathode end in this study. The limit
      of detection (LOD) at a signal-to-noise ratio=3 for phiX174 RF DNA-Hae III digest
      prepared in 50 mM Tris-borate, pH 10.0, was down to 0.171 ng/ml, with an 860-fold
      improvement (compared to that obtained by 10-s injection at 25 V/cm) in the
      sensitivity, when injecting about 2.58 microl. By applying a short plug (2.3 cm)
      of 0.5 mM AgNO3 prepared in 1.5% PEO solution after sample injection, the
      analysis of up to 0.75 microl DNA prepared in phosphate-buffered saline (PBS) has
      been carried out without any tedious desalting processes. This results in an LOD
      of 6.86 ng/ml for the DNA sample and a 155-fold improvement in the sensitivity.
      Moreover, this method has allowed the analysis of 0.75 micro] of polymerase chain
      reaction products amplified after 18 cycles with good reproducibility.

PMID- 12214695
TI  - Determination of nitrate in seawater by capillary zone electrophoresis with
      chloride-induced sample self-stacking.
AB  - A capillary zone electrophoresis (CZE) method was established to determine low
      concentration nitrate which was online preconcentrated with chloride-induced
      leading-type sample self-stacking for seawater samples. The sample self-stacking
      was based on transient isotachophoresis in which chloride served as leading ion,
      and dihydrogenphosphate in the background electrolyte (0.1 M phosphate) as the
      terminating one. Due to the small mobility difference between nitrate and
      chloride, the isotachophoresis time was so long that nitrate could not separate
      from the rear sharp boundary between chloride and the background electrolyte
      (BGE) when it migrated to the detection window. A zwitterionic surfactant, 3-(N,N
      dimethyldodecylammonio)propane sulfonate was added to the BGE to enlarge the
      mobility difference for its selective interaction with anions. Thus, a highly
      conductive sample could be injected in a large volume with about fourfold
      sensitivity enhancement compared to that of field amplification sample stacking
      in which nitrate was dissolved in pure water. The relative standard deviations
      (n=5) of migration time, peak area, peak height were 0.1, 3.0, 1.5%,
      respectively. The limit of detection (S/N=3) for nitrate was 35 microg/l in
      seawater samples with relatively low concentration BGE (0.1 M sodium phosphate,
      pH 6.2). The overall procedure consisting of online preconcentration and
      separation was as simple as routine CZE except for a slightly longer sample
      injection time (3-4 min).

PMID- 12214696
TI  - Simultaneous capillary electrophoretic separation and detection of P(V) and As(V)
      As heteropoly-blue complexes.
AB  - A capillary electrophoretic (CE) method was developed for the simultaneous
      determination of P(V) and As(V). A Mo(VI)-ascorbic acid reagent reacted with a
      mixture of trace amounts of P(V) and As(V) to form the corresponding heteropoly
      blue complexes in 0.05 M acetate buffer (pH 3.5). When 0.05 M malonate buffer was
      used as a migration buffer, the peaks due to their migrations were well separated
      in the electropherogram, and the pre-column complex-formation reaction was
      applied to the simultaneous CE determination of P(V) and As(V) with direct UV
      detection at 220 nm. With the proposed method, the calibration curves were linear
      in the concentration range of 5 x 10(-7) - 1 x 10(-4) M, with a detection limit
      of 1 x 10(-7) M (a signal-to-noise ratio of 3). Interference from foreign ions
      was also discussed.

PMID- 12214697
TI  - Chiral liquid chromatography separation and chiroptical properties of the
      enantiomers of dimethyl alpha-hydroxyfarnesylphosphonate, a precursor of a
      farnesyl protein transferase inhibitor.
AB  - The HPLC enantiomeric separation of racemic and non-racemic samples of dimethyl
      alpha-hydroxyfarnesylphosphonate (1) was accomplished using Chiralcel OD as
      chiral stationary phase. Single enantiomers were isolated by semipreparative HPLC
      and their CD spectra and optical rotations were measured. The method ascertains
      enantiomeric excess of 1, obtained by oxidation of dimethylfarnesylphosphonate
      with enantiopure oxaziridines, avoiding converting the enantiomers to
      diastereomers by the use of a chiral auxiliary. Stability of the solutions of 1
      is strongly dependent on the nature of the solvent.

PMID- 12214698
TI  - Single column approach for the liquid chromatographic separation of polar and non
      polar glucosinolates from broccoli sprouts and seeds.
AB  - Ion-pair and hydrophilic interaction chromatographies are considered to be
      complementary methods of choice for analyzing intact glucosinolates from
      broccoli. Ion-pair chromatography resolves non-polar glucosinolates, such as
      those containing indole moieties, while hydrophilic interaction chromatography is
      superior for separating polar glucosinolates, such as glucoraphanin and
      glucoiberin. Reversed-phase separations using hydrophilic endcapped C18-bonded
      silica and a 50 mM ammonium acetate-methanol gradient mobile phase resolve both
      polar and non-polar glucosinolates negating the need for switching columns.

PMID- 12214699
TI  - Volatile components from Anthriscus sylvestris (L.) Hoffm.
AB  - The volatile components of fresh leaves and roots from Anthriscus sylvestris (L.)
      Hoffm., obtained through hydrodistillation, were analysed by GC and GC-MS. This
      was compared to dichloromethane extracts of both fresh and dried leaf and root
      material. The monoterpene fraction (69-70%) dominated, while beta-phellandrene
      (39-45%) was the main component in both the leaf and the root oil. Other
      components in the leaf oil were beta-myrcene (17%), sabinene (6.2%), Z-beta
      ocimene (5.4%) and benzene acetaldehyde (4.1%). In the roots we found Z-beta
      ocimene (16.9%) and alpha-pinene (4.6%) as other major components. These
      principle constituents of both essential oils were also present in the
      dichloromethane extracts of the fresh and dried leaves and the roots, although in
      much smaller percentages. Comparing hydrodistillation of fresh plant material
      with a dichloromethane extract, the latter yielded a considerably lower amount of
      constituents. In addition, air drying and freeze drying resulted in a significant
      loss of volatile constituents as compared to fresh material (dichloromethane
      extract).

PMID- 12214700
TI  - Determination of alkylphosphonic acids using micellar electrokinetic
      chromatography with laser-induced fluorescence detection and high-salt stacking.
AB  - Methyl-, ethyl- and propylphosphonic acids (MPA, EPA, and PPA, respectively) were
      derivatized with panacyl bromide in dry N,N-dimethylformamide (DMF). After mixing
      with a high-salt dilution buffer, the derivatives were separated by micellar
      electrokinetic chromatography in 35 min and detected by laser-induced
      fluorescence (He-Cd laser excitation at 325 nm and detection at 500 nm). Baseline
      resolution was achieved using a separation buffer containing 50 mM sodium
      cholate, 40% (v/v) of acetonitrile and 50 mM borate. Addition of 400 mM NaCl to
      the dilution buffer allowed the injection time to be increased to 30 s while
      still maintaining baseline resolution. Limits of detection for MPA, EPA, and PPA
      were 0.13 microM (12 ppb), 0.13 microM (14 ppb) and 0.14 microM (17 ppb)
      injected, respectively. The reproducibility of corrected peak area at 15 microM
      was 3.7 approximately 4.3%.

PMID- 12214701
TI  - On-column complexation of metal ions using 2,6-pyridinedicarboxylic acid and
      separation of their anionic complexes by capillary electrophoresis with direct UV
      detection.
AB  - On-column complexation of metal ions with 2,6-pyridinedicarboxylate (2,6-PDC) to
      form anionic complexes enabled their separation by capillary zone electrophoresis
      with direct UV detection at 214 nm. Nine metal ions, Cu2+, Zn2+, Ni2+, Cd2+ Mn2+,
      Pb2+, Fe3+, Al3+ and Ca2+, were determined in less than 7 min using 10 mM 2.6-PDC
      solution containing 0.75 mM tetradecyltrimethylammonium bromide at pH 4.0.
      Satisfactory working ranges (20-300 microM), detection limits (3-10 microM) and
      good repeatability of the peak areas (RSD 2.1-4.2%, n=5) were obtained using
      hydrodynamic injection (30 s). The proposed method was used successfully for the
      determination of Mn2+, Fe3+, Al3+ and Ca2+ in groundwaters.

PMID- 12214702
TI  - Gradient separation of polymers at critical point of adsorption.
AB  - Theoretical and experimental analysis of interaction polymer chromatography
      revealed a new mode of polymer separation: gradient elution at the critical point
      of adsorption (the eluent composition where size-exclusion and adsorption
      interactions completely compensate each other). This mode allows for molecular
      mass-independent separation by chemical composition and/or other structural
      differences between macromolecules. The isocratic and gradient elution of narrow
      polydispersity polystyrenes and poly(methylmethacrylates) on reversed- and normal
      phase columns confirmed all basic theoretical assumptions and conclusions. The
      gradient separation of poly(alkylmethacrylate) and poly(alkylacrylate) blends, as
      well as styrene-butadiene copolymers provided further experimental verification
      of the theory.

PMID- 12214703
TI  - Composition analysis of poly(ethylene glycol)-poly(L-lactide) diblock copolymer
      studied by two-dimensional column chromatography.
AB  - We used two-dimensional column chromatography to analyze the composition of a
      sample of presumably a diblock copolymer of poly(ethylene glycol) (PEG) and
      poly(L-lactide) synthesized from monomethoxy-terminated PEG. The first dimension
      of the separation is phase fluctuation chromatography to prepare fractions that
      contain various components of the copolymer in different ratios. The second
      dimension is size-exclusion chromatography, NMR, and HPLC at the critical
      condition of PEG. The PEG initiator has small amounts of diol-terminated dimeric
      components. We found that the copolymer sample contains a triblock copolymer and
      low-molecular-mass components in addition to the main part of the diblock
      copolymer. The SEC chromatograms show that the main part consists of two
      components with distinct peak lengths for the PLLA block. The low-molecular-mass
      components have a broad distribution in chemical composition. Phase fluctuation
      chromatography enriched the triblock copolymer and the diblock copolymer with the
      longer PLLA block in early fractions when the column was packed with
      carboxymethyl-modified porous silica. When the porous medium was PLLA-grafted
      silica, size exclusion dominated, but the low-molecular-mass components were
      separated according to their chemical composition.

PMID- 12214704
TI  - High-performance liquid chromatographic separation of polycyclic aromatic
      hydrocarbons using pyridinium chloride as a selective fluorescence quencher to
      aid detection.
AB  - The first use of pyridinium chloride (PC), as a selective fluorescence quenching
      agent of alternant polycyclic aromatic hydrocarbons (PAHs), under HPLC separation
      conditions is reported. PC was found to be superior to nitromethane, the only
      reported PAH selective quencher used in HPLC. The mobile phase addition of 0.03 M
      PC greatly simplifies the observed fluorescence-detected chromatograms for
      complex PAH mixtures, facilitating PAH identification. Stern-Volmer quenching
      constants (K(sv)) for PAHs were calculated from the chromatograms obtained under
      isocratic and gradient conditions and found to be similar. The K(sv) values were
      shown to be useful in establishing peak purity.

PMID- 12214705
TI  - Rapid characterization of anthocyanins in red raspberry fruit by high-performance
      liquid chromatography coupled to single quadrupole mass spectrometry.
AB  - Anthocyanins from red raspberries were extracted from the fruit by homogenizing
      in acidified methanol. The methanolic extract was centrifuged and the supernatant
      analyzed by reversed-phase HPLC. The eluent was monitored at 371 and 520 nm
      before being introduced into a single quadrupole mass spectrometer through an
      atmospheric pressure chemical ionization probe operating in positive ion mode.
      This method allowed the identification of eight anthocyanins. In the absence of
      readily available reference compounds, approaches that can be taken to analyse
      anthocyanins by HPLC with absorbance and mass spectrometric detection are
      discussed.

PMID- 12214707
TI  - Immobilized artificial membrane chromatography coupled with atmospheric pressure
      ionization mass spectrometry.
AB  - Liquid chromatographic separations on monolayers of cell membrane phospholipids
      covalently immobilized to silica particles at high molecular density is used for
      mimicking solute partitioning into biological membranes that generally correlates
      with membrane transport. This technique called immobilized artificial membrane
      chromatography usually employs ultraviolet (UV) detection where a single compound
      is analyzed in a chromatographic run limiting thereby its throughput for drug
      discovery applications. For coupling with atmospheric pressure ionization mass
      spectrometry, the phosphate-buffered saline mobile phase was replaced with one
      that used ammonium acetate as a volatile buffer. While atmospheric pressure
      chemical ionization accommodated a purely aqueous effluent, interfacing with
      electrospray ionization required effluent splitting and the addition of an
      organic modifier (5%, v/v, acetonitrile). Neuropeptide FF antagonists as early
      phase drug candidates were used for the comparative evaluation of the methods.
      Whereas electrospray ionization produced essentially no fragment ions, several
      compounds involved in our study yielded low-abundance molecular ions with
      atmospheric pressure chemical ionization. The use of mass spectrometry yielded
      data that correlated well with those obtained by the method employing UV
      detection. Both atmospheric pressure ionization methods permitted the
      simultaneous determination of the k'(IAM), capacity factors and, therefore, an
      increased-throughput ranking of potential new leads emerged from the drug
      discovery process based on affinity to artificial membranes.

PMID- 12214706
TI  - Chromatographic characterisation of an estrogen-binding affinity column
      containing tetrapeptides selected by a combinatorial-binding approach.
AB  - In our work we performed a combinatorial synthesis in aqueous medium to prepare
      peptide libraries from which we would select amino acid sequences with binding
      properties towards estrogens. We prepared an affinity solid-phase by using a
      tetrapeptide with good selectivity and affinity towards the estradiol (K> 10(4)
      M(-1)). Samples of estrogens in buffer, in tap water and in river water were
      applied to our column in which they were retained (k' > 116). These could only be
      eluted in a few millilitres of methanol mobile phase. In all cases there were
      quantitative recoveries. The pre-concentration studies were promising.

PMID- 12214708
TI  - Simultaneous determination of amino acids and carbohydrates by anion-exchange
      chromatography with integrated pulsed amperometric detection.
AB  - A direct, sensitive, simple and practical method for simultaneous determination
      of amino acids and carbohydrates by anion-exchange chromatography with integrated
      pulsed amperometric detection was developed. The retention behavior of amino
      acids and carbohydrates on the anion-exchange column and the detection of amino
      acids and carbohydrates at different integrated pulsed amperometric detection
      waveforms were investigated. The optimized gradient eluent conditions for
      analysis of 17 amino acids and nine carbohydrates were obtained. Separation time
      was 100 min. Detection limits for amino acids and carbohydrates were 5.2-207.1 nM
      under injection volume of 25 microl. The RSDs of peak area were 1.2-3.3%. The
      calibration graphs of peak area for the analytes were linear over about three
      orders of magnitude with a correlation coefficient of 0.9950-0.9999. The method
      was applied to determine amino acids and carbohydrates in a liquid condiment with
      satisfactory results.

PMID- 12214709
TI  - Oligonucleotide trapping method for purification of transcription factors.
AB  - A new oligonucleotide trapping method in which a decameric oligonucleotide (AC)5
      coupled to Sepharose is used to trap a complex of a transcription factor and its
      corresponding specific DNA element is described. The concentration of DNA element
      used in the trapping method was very low (50 nM) and hence discouraged binding of
      nonspecific proteins. We have shown that this method gives higher purity for
      green fluorescent protein CAAT enhancer binding chimeric protein (GFP-C/EBP) than
      the biotin-avidin method. We have also shown that the oligonucleotide trapping
      method has a capacity close to 95% of the theoretical capacity, which is
      significantly greater than the 15% capacity obtained with conventional DNA
      affinity columns. The purity of GFP-C/EBP obtained using a low concentration of
      the oligonucleotide in our trapping method is three-fold higher (3,668- versus
      1,028-fold) than that obtained by conventional DNA affinity chromatography and
      the yield was also higher (36% versus 24%). Highly purified transcription factor
      B3 is obtained from Xenopus egg crude extract using the oligonucleotide trapping
      method as the only purification.

PMID- 12214710
TI  - Millennium Ecosystem Assessment: a healthy drive for an ailing planet.

PMID- 12214712
TI  - Increasing the microbial activity in activated sludge by the phenomenon of
      'biological resonance.
AB  - Mechanical oscillations as well as electrical oscillations (e.g. in an electrical
      oscillatory circuit) can lead to resonance conditions by external agitation with
      the natural frequency of the system. During the microbial protein synthesis, the
      induction and repression mechanisms also cause oscillations in the form of
      varying protein concentrations. The aim of this work concentrates on an induced
      resonance case of the biological system, comparable with physical resonance
      phenomena, by external periodic stimulations. For this, system theoretical
      computer simulations with a structured genetic model were carried out, which
      built the theoretical fundament for describing the effect of 'Biological
      Resonance'. Based on that, lab-scale experiments using a mixed microbial culture
      (activated sludge) and skimmed milk as an inducing substrate revealed an enhanced
      microbial productivity of around 60%-75% compared to values of the productivity
      under steady-state conditions in a narrow range of process parameters. The
      optimum (resonance case) was confirmed by a repetition of the variation
      experiments and is characterised by a substrate supply period of approx. 18 min
      and a following starvation period of about 9 min. Long-term investigations under
      optimised process conditions indicate adaptation mechanisms of the microorganisms
      to evade the imposed stress conditions. The productivity will not remain constant
      without additional stimulation and declines to its original level. However,
      temporal modulation of the starvation period permanently increases the
      productivity (elevated catabolism) to about 60%, which was observed over a period
      of several weeks.

PMID- 12214711
TI  - Power analysis as a reflexive scientific tool for interpretation and
      implementation of the precautionary principle in the European Union.
AB  - The diversity of interpretation, the subsequent lack of implementation, and the
      enforcement of the precautionary principle have been important issues in the
      European environmental discourse for the past five years. The European Commission
      published a communication on the Commission's interpretation of the precautionary
      principle on February 2nd, 2000. However, the distinction between precaution and
      prevention is absent in the EU Commission's interpretation, resulting in the
      communication's lacking relevance for the precautionary principle. The important
      consequence of the precautionary concept in policy and decision-making is that it
      should not be based on an assumed certainty of the certainty of environmental
      knowledge--but rather on a certainty of the uncertainty of environmental
      knowledge. In other words, the regulation should, to a greater extent, be based
      on the management of uncertainty, and risk assessments should explicitly present
      and discuss related uncertainty and lack of knowledge. The management of
      uncertainty should be based on setting the acceptable level of risk of accepting
      a failure to reject the null hypothesis of no adverse effects (beta). This is
      done by setting the required power (1-beta) according to a socioeconomic cost
      benefit analysis. Moreover, the acceptable ecological effect size (A) could also
      be set a priori which would have implications for the power of a study. Reversal
      of the burden of proof could be considered in order to resolve possible legal
      implications for the risk managers.

PMID- 12214713
TI  - Carbonyls in the metropolitan area of Mexico City: calculation of the total
      photolytic rate constants Kp(s(-1)) and photolytic lifetime (tau) of ambient
      formaldehyde and acetaldehyde.
AB  - A great number of studies on the ambient levels of formaldehyde and other
      carbonyls in the urban rural and maritime atmospheres have been published because
      of their chemical and toxicological characteristics, and adverse health effects.
      Due to their toxicological effects, it was considered necessary to measure these
      compounds at different sites in the metropolitan area of Mexico City, and to
      calculate the total rate of photolytic constants and the photolytic lifetime of
      formaldehyde and acetaldehyde. Four sites were chosen. Sampling was carried out
      at different seasons and atmospheric conditions. The results indicated that
      formaldehyde was the most abundant carbonyl, followed by acetone and
      acetaldehyde. Data sets obtained from the 4 sites were chosen to calculate the
      total rate of photolysis and the photolytic lifetime for formaldehyde and
      acetaldehyde. Maximum photolytic rate values were obtained at the maximum actinic
      fluxes, as was to be expected.

PMID- 12214714
TI  - Volatile hydrocarbons in the atmosphere of Athens, Greece.
AB  - This work presents the results of one-year monitoring study of Volatile
      Hydrocarbons, VHCs, in the atmosphere of Athens. It is the first systematic
      attempt to determine the VHC levels in the Athens' atmosphere with the very well
      known photochemical pollution problems. The purpose of this work was to create a
      database concerning VHCs in order to evaluate the photochemical pollution in this
      area (ozone creation, case studies and meteorology). Totally, 308 samples were
      collected at three different sites used in the state-monitoring programme
      involving the criteria pollutants. Air samples were collected on Tenax TA tubes
      and analysed by thermal desorption and dual column GC dual FID. Fifteen selected
      compounds were studied; 6 alkanes and 9 benzenoid compounds. The measured values
      of individual alkanes ranged from 0.39 pg m(-3) to 33 pg m(-3), and those of
      aromatics from 0.20 pg m(-3) to 616 pg m(-3). The sum of all 15 VHC
      concentrations ranged between 16 and 1697 pg m(-3). The time and spatial
      variations in the concentration of these compounds were assessed. Volatile
      hydrocarbons exhibited a clear seasonal and time cycle, showing higher
      concentrations during winter and early morning hours. Study of the spatial
      variations of VHC levels showed higher concentrations at the center of the city.
      The variation of toluene/benzene ratio and the correlation between VHCs, criteria
      pollutants (CO, NOx and O3) and meteorological parameters were also assessed. It
      was demonstrated that a trip-line of the VHCs concentration at the city center
      doubles the ozone concentration at peripheral areas under favourable
      meteorological conditions.

PMID- 12214715
TI  - Human exposure to dioxins and furans: application of the substance flow analysis
      to health risk assessment.
AB  - Substance Flow Analysis (SFA) is an important instrument that allows for the
      undertaking of environmental management for a specific contaminant. 'Control
      Analysis' is a tool that assesses the effect on a target flow of changes in flows
      forming part of a control basis set. The purpose of the present study was to
      perform a modeling of the annual PCDD/F flows in Tarragona Province and to apply
      the model for human health risk assessment. The validation of the model has been
      evaluated by comparing estimated fluxes with experimental values. Eleven
      subsystems, as well as a set of 88 flows of the system in Tarragona Province were
      considered. The total PCDD/F accumulation in Tarragona Province was between 62.6
      and 159.5 g I-TEQ/y. Accumulation in sediments (27.9-74.6 g I-TEQ/y) and soils
      (35.0-80.8 g I-TEQ/y) are the two principal modes of deposition. Estimated flow
      in human adipose tissue means a mean intake of PCDD/F (via ingestion and
      inhalation) of 243 pg I-TEQ/person/day. The food chain pathway accounts for 99%
      of the total daily intake. As a result of the simulation, a 100% decrease in
      industrial emissions would cause a 1.7% reduction in the PCDD/F accumulation in
      humans. In turn, a 100% reduction of PCDD/Fs in the industrial waste waters would
      cause only an insignificant 0.1% decrease in the accumulation of PCDD/Fs in
      humans.

PMID- 12214716
TI  - Agricultural soil as a potential source of input of organochlorine pesticides
      into a nearby pond.
AB  - A study was conducted in the southeastern region of Buenos Aires province,
      Argentina, to assess an agricultural soil as a potential source of organochlorine
      (OC) pesticides for the aquatic biota of a nearby pond. We analyzed gamma-HCH
      (lindane), still in use, and the following banned compounds: DDT, DDE, DDD
      heptachlor, heptachlor epoxide, aldrin, dieldrin and endrin in soil, bulrush,
      grass shrimp and fish using gas chromatography with electron capture detection
      (GC-ECD). Among the OC pesticides, lindane was most dominant in the soil (32.6
      ng/g dry wt in the upper and 173.9 ng/g dry wt in the lower horizon) and bulrush
      (1.9 pg/g lipid). Macrophyte also accumulated high levels of heptachlor epoxide
      (1.5 pg/g lipid). Heptachlor, although present in the soil, was below the
      detection limit in all aquatic biota studied. Its primary degradation product,
      heptachlor epoxide, was found in both soil and biota samples. DDT was found at
      low levels in the surface soil (6.8 ng/g dry wt), but at higher concentrations in
      fish (3.6 pg/g lipid), although levels were still below permissible levels for
      human consumption. Since most of the compounds were found in both soil and
      aquatic biota, our study suggests that agricultural soil could be an important
      source for OC pesticides in the nearby pond.

PMID- 12214717
TI  - Small-scale variability of metals in soil and composite sampling.
AB  - Soil pollution data is also strongly scattering at small scale. Sampling of
      composite samples, therefore, is recommended for pollution assessment. Different
      statistical methods are available to provide information about the accuracy of
      the sampling process. Autocorrelation and variogram analysis can be applied to
      investigate spatial relationships. Analysis of variance is a useful method for
      homogeneity testing. The main source of the total measurement uncertainty is the
      uncertainty arising from sampling. The sample mass required for analysis can also
      be estimated using an analysis of variance. The number of increments to be taken
      for a composite sample can be estimated by means of simple statistical formulae.
      Analytical results of composite samples obtained from different fusion procedures
      of increments can be compared by means of multiple mean comparison. The
      applicability of statistical methods and their advantages are demonstrated for a
      case study investigating metals in soil at a very small spatial scale. The paper
      describes important statistical tools for the quantitative assessment of the
      sampling process. Detailed results clearly depend on the purpose of sampling, the
      spatial scale of the object under investigation and the specific case study, and
      have to be determined for each particular case.

PMID- 12214718
TI  - A new approach for biological online testing of stack gas condensate from
      municipal waste incinerators.
AB  - A biological testing system for the monitoring of stack gas condensates of
      municipal waste incinerators has been developed using Euglena gracilis as a test
      organism. The motility, velocity and cellular form of the organisms were the
      endpoints, calculated by an image analysis system. All endpoints showed
      statistically significant changes in a short time when organisms were exposed to
      samples collected during combustion situations with increased pollutant
      concentrations. The velocity of the organisms proved to be the most appropriate
      endpoint. A semi-continuous system with E. gracilis for monitoring stack gas
      condensate is proposed, which could result in an online system for testing stack
      gas condensates in the future.

PMID- 12214719
TI  - Assessment of the sustainability of technology by means of a thermodynamically
      based life cycle analysis.
AB  - Life cycle analysis is one of the tools in the assessment of the sustainability
      of technological options. It takes into account all effects on the ecosystem and
      the population which may endanger the possibilities of current and future
      generations. However, the main bottleneck in current LCA methodologies is the
      balancing of different effects, being all quantified on different scales. In this
      work, a methodology is proposed, which allows one to quantify different effects
      of the production, consumption and disposal of goods, and services on a single
      scale. The basis of the methodology is the second law of thermodynamics. All
      production, consumption and disposal processes affecting the ecosystem and the
      population, are quantified in terms of loss of exergy. The exergy content of a
      material is the maximum amount of energy which can be transformed into work at
      given environmental conditions. Next to the elaboration of the methodology, the
      new approach is illustrated by examples of the production of synthetic organic
      polymers, inorganic building insulation materials and different waste gas
      treatment options.

PMID- 12214721
TI  - The role of colposcopy in modern gynecology.
AB  - The purpose of this review is to demonstrate that colposcopy, introduced in 1925-
      which is, notably before the development of great technological advances in
      modern gynecology--continues to be a valid technique without essential
      innovations to the original method described at the beginning of the last
      century. Colposcopy was developed in Germany during the rise of Nazism with the
      Second World War being an important barrier for the spread and diffusion of the
      technique. Colposcopy, however, continued to progress in a few countries such as
      Spain, Italy, Brazil, France and Switzerland. When colposcopy was introduced in
      the United States during the 70s, its use was mostly restricted to specialists
      who were almost exclusively dedicated to cervical pathology and knowledgeable
      about cytopathology, anatomic pathology, and colposcopy and who were competent
      both in the diagnosis and treatment of cervical lesions. These circumstances were
      completely different from what happened in the majority of European countries
      where colposcopists were trained as gynecologists and their histocytological
      knowledge, which was focused on the lower genital tract, was somewhat more
      extensive than that acquired by specialists in gynecology. There are two clearly
      different trends in relation to the use of colposcopy with characteristic
      geographic distribution: countries with an Anglo-Saxon influence in which
      colposcopy is performed selectively, and countries with a German medical
      inheritance in which colposcopy is carried out routinely during a standard
      general gynecological consultation. However, this difference is not restrictive
      and by no means can it be stated that colposcopy is systematically being used by
      all European or Latin American gynecologists for reasons related to training in
      the colposcopic technique. In 1977, we introduced the concept of dynamic
      colposcopy with the aim of differentiating it from the descriptive immobility of
      the original classification of Hinselmann (1954) that had remained almost
      unchanged by his immediate followers. Briefly, the objective was to turn
      colposcopy into a diagnostic tool able to identify the pathological substrate
      corresponding to traditional colposcopic images. We established ten differential
      signs that allow us to classify an ATZ area as subsidiary or not to be biopsied.
      The classification system proposed in Rome (International Federation of Cervical
      Pathology and Colposcopy [IFCPC], 1990) supports our original concept because by
      identifying major or minor changes in the original images, a diagnosis of the
      severity of the lesion can be established. With regard to specificity, the
      figures range between 48% and 10% with 96% for sensitivity. Obviously, a wide
      range of colposcopic specificity must be related to the expected efficacy of the
      method. When after biopsy of an atypical colposcopic image, only a low-grade
      lesion is detected, should this be considered a false positive colposcopic
      result? Although histopathologic findings are accepted as the "gold
      standard"...it is well known that a certain degree of subjectivity can be
      present. Inter- and intra-observer differences (when the same pathologist is
      reviewing the diagnosis after a certain time lapse) may be present. It has been
      argued that microbiopsy under colposcopic control gives rise to a wide error
      range and that it cannot be considered representative of the lesion. It is likely
      that this situation may occur when colposcopy-guided biopsy is performed by
      inexperienced hands or when biopsy is limited to small and insufficient sampling.
      A very important colposcopic sign, such as complete visual inspection of the
      squamocolumnar junction is frequently missed. Any lesion with boundaries in the
      endocervix, cannot be simply assessed by means of microbiopsies from the
      ectocervix unless there is no doubt regarding the severity of the lesions.
      Microcolpohysteroscopy (MCH) may be of great value in these cases by showing the
      limits of endocervical involvement. CONCLUSIONS: According to the evidence
      presented here, it can be concluded that "colposcopy is in good health" and that
      probably the popularity of this technique in the field of gynecology would
      increase if cytopathologists and gynecologists' tasks were limited to their own
      fields rather than turning them into improvised specialists for their counterpart
      disciplines. The coordinating role of the gynecologist as a specialist for
      integral women's health should continue to be defended and in this respect,
      colposcopy should be considered a routine technique in daily practice.

PMID- 12214720
TI  - Man-made chemicals found in remote areas of the world: the experimental
      definition for POPs.
AB  - Members of the United Nations Economic Commission for Europe (UN-ECE) signed a
      legally binding protocol on persistent organic pollutants (POPs) in February 1998
      under the Convention on Long-Range Transboundary Air Pollution. A treaty that
      intends to control the production, import, export, disposal and use of toxic
      chemicals that persist for decades in the environment has been formally signed at
      a conference in May 2001 in Stockholm. The 2001 POP treaty, like the 1998 LRTAP
      POP protocol, contains a provision on adding further chemicals to the initial
      group of twelve or fifteen. The occurrence of a compound or a group of compounds
      in so called remote and pristine areas, e.g. in the Artic or in the Southern
      Hemisphere, proves its stability under the chemical and biological conditions of
      the environment. Compounds identified in this way, in samples taken primarily in
      very remote regions of the planet, are classified by their environmental fate and
      global distribution as persistent organic pollutants (POPs), regardless of any
      political assessments.

PMID- 12214722
TI  - Endometrial adenocarcinoma presented with enterouterine fistula.
AB  - Presentation of endometrial adenocarcinoma with an ileouterine fistula as an
      initial symptom is exceptionally rare. Besides a report on such case we give a
      brief review of the literature on this subject. The case is a 77-year-old woman
      with an ileouterine fistula caused by endometrial adenocarcinoma. The uterus and
      the small bowel were removed en bloc followed by colostomy. The patient was
      referred for radiation therapy to be followed with six cycles of carboplatin and
      5FU.

PMID- 12214723
TI  - Impact of maintenance chemotherapy on disease-free survival in patients with
      stage Ic and II epithelial ovarian cancer.
AB  - PURPOSE OF INVESTIGATION: To evaluate the impact on disease free survival (DFS)
      with maintenance chemotherapy following complete surgery and adjuvant
      chemotherapy in patients with stage Ic and II epithelial ovarian cancer by a
      retrospective study. METHODS: One hundred and forty patients with stage Ic and
      stage II epithelial ovarian cancer were classified into three groups according to
      the modality of maintenance chemotherapy (no therapy, oral or intravenous
      administration of anti-cancer drugs). DFS was compared among the three groups,
      and independent predictive factors for relapse were analyzed. RESULTS: There were
      no statistically significant differences in DFS among the three groups for either
      stage Ic or II cancers, stage Ic and stage II. Multivariate analysis revealed
      that independent predictive factors for relapse were stage II (p = 0.004) in all
      patients and less than three cycles of adjuvant chemotherapy in stage II patients
      (p = 0.015). CONCLUSION: Maintenance chemotherapy had no impact on DFS in
      patients with stage Ic or II epithelial ovarian cancer.

PMID- 12214724
TI  - The role of topotecan as second-line therapy in patients with recurrent ovarian
      cancer.
AB  - INTRODUCTION: Up to 80% of patients with advanced ovarian cancer will recur
      following first-line platinum containing chemotherapy. Topotecan has recently
      been used as a second-line agent in treatment of advanced ovarian disease. The
      aim of the study was to evaluate the effect of topotecan on response rate and
      progression-free interval on patients with recurrent ovarian cancer who had been
      treated with platinum-containing first-line chemotherapy. METHODS: A
      retrospective review of all cases of recurrent ovarian cancer treated with
      topotecan was done. Response was determined using radiologic reports (CT scans,
      ultrasound scans), CA-125 level and the clinical evaluation. Response type was
      determined using World Health Organization (WHO) criteria. RESULTS: Between 1998
      2000, a total of 43 patients were treated with topotecan. Median age was 57
      (range 41-80), 40/43 patients had stage III and IV, 37/43 patients had Grade 3
      tumors. Seventeen of 43 patients (39.5%) demonstrated stable disease and 9/43
      (21%) patients demonstrated partial response. Median time to response was eight
      weeks, median progression-free interval was 31 weeks and median time of follow-up
      and survival was 48 weeks. CONCLUSION: Topotecan is considered a reasonable
      option for treatment of patients with recurrent ovarian cancer that have failed
      previous treatment with platinum-containing chemotherapy.

PMID- 12214725
TI  - Synchronous and metachronous extrapelvic metastases of cancer of the cervix: a
      study of prognosis and palliation.
AB  - Thirty-eight women with cancer of the cervix and extrapelvic metastases (EPM)
      were retrospectively reviewed with respect to prognosis and responses to
      palliative radiotherapy. Seventeen patients had synchronous EPM and 21
      individuals displayed metachronous metastatic disease outside of the pelvic
      cavity. A meaningful difference was not revealed (p = 0.11) in the comparison of
      the two groups' 2-year survival rates. However, this small retrospective review
      highlighted the efficacy of radiotherapy administered for palliation to this
      cohort of patients.

PMID- 12214726
TI  - CT findings in two cases of port-site metastasis after laparoscopy for ovarian
      cancer.
AB  - CASES: Two patients with histologically proven port-site metastasis following
      laparoscopic procedures for ovarian cancer underwent a CT scan. These two
      patients were initially treated for a stage IA and III ovarian cancer. Port-site
      recurrence occurred six and 19 weeks following the laparoscopic procedure. In one
      patient, the abdominal wall recurrence was associated with peritoneal carcinosis.
      In both patients, CT scan revealed the presence of an heterogeneous nodular
      lesion inside the left oblique muscle. Histologic analysis confirmed the
      diagnosis of port-site recurrence. CONCLUSIONS: Port-site metastases could be
      observed in the treated patients with a laparoscopic approach for ovarian cancer.
      When this diagnosis is clinically suspected, a CT scan should be performed in
      order to precise the diagnosis of port-site metastasis and to evaluate potential
      intra-abdominal recurrent disease. However, only histologic examination can
      confirm a diagnosis of port-site recurrence.

PMID- 12214727
TI  - The prognostic relevance of histological type in uterine sarcomas: a Cooperation
      Task Force (CTF) multivariate analysis of 249 cases.
AB  - PURPOSE OF INVESTIGATION: The objective of this retrospective multicenter study
      was to assess the prognostic relevance of histologic type in uterine sarcomas.
      METHODS: The hospital reports of 249 patients with uterine sarcomas were
      reviewed. Surgery was the initial therapy for all patients. Histologic type was
      leiomyosarcoma in 95 cases, low-grade endometrial stromal sarcoma (ESS) in 19,
      high-grade ESS in 34, and carcinosarcoma in 101. Postoperative treatment was
      given without well-defined protocols. Median follow-up of survivors was 97
      months. RESULTS: In the whole series 2-year, 5-year, and 10-year survival rates
      were 53.5%, 41.6%, and 35.8%, respectively, and median survival was 31 months. At
      univariate analysis survival was significantly related to stage (p = 0.0001),
      mitotic count (p = 0.0001), and histologic type (low-grade ESS vs leiomyosarcoma
      vs carcinosarcoma vs high-grade ESS, median: not reached vs 27 months vs 21
      months vs 16.5 months, p = 0.0011), but not to postoperative therapy and patient
      age. The Cox model revealed that tumor stage, mitotic count and histologic type
      were independent prognostic variables for survival. In detail, the risk of death
      was significantly lower for low-grade ESS (risk ratio [RR] = 0.257; 95%
      confidence interval [CI] = 0.071-0.931) and carcinosarcoma (RR = 0.509; 955 CI =
      0.324-0.799) when compared to leiomyosarcoma. Conversely, no significant
      difference in survival was found between leiomyosarcoma and high-grade ESS.
      CONCLUSIONS: Histologic type is an independent prognostic variable for survival
      in uterine sarcomas. Low-grade ESS has the best clinical outcome, whereas
      leiomyosarcoma has the poorest one. It is noteworthy that, when adjusting for
      stage and mitotic count, leiomyosarcoma has a significantly worse prognosis than
      carcinosarcoma.

PMID- 12214728
TI  - Uterine papillary serous carcinoma (pure and mixed type) compared with moderately
      and poorly differentiated endometrioid carcinoma. A clinicopathologic study.
AB  - OBJECTIVE: The aim of this study was to investigate the clinicopathologic
      features and the outcome in patients with pure and mixed type uterine papillary
      serous carcinoma (UPSC), and to compare these parameters with those observed in
      patients with moderately and poorly differentiated endometrioid endometrial
      carcinoma (MPD-EEC). METHODS: The charts of 34 patients with UPSC and 30 patients
      with MPD-EEC, operated on between January 1995 and December 2000, were
      retrospectively reviewed. The UPSC group included ten cases of pure and 24 cases
      of mixed type UPSC (admixed with endometrioid component). All patients had
      undergone full surgical staging. Clinical features, surgicopathological findings,
      recurrence rate and recurrence-free interval were compared between the study
      groups. RESULTS: Significantly more patients with MPD-EEC than with UPSC were
      operated on in FIGO stage I and II (p = 0.001). MPD-EEC patients were
      significantly older and more obese (p = 0.03 and p = 0.01, respectively) as
      compared with the UPSC patients. Significantly more patients with MPD-EEC
      presented with postmenopausal bleeding (p = 0.02), had a second primary cancer in
      the past (p = 0.03) and had a first degree relative with history of malignant
      disease (p = 0.0001). Conversely, the rates of positive abdominal cytology and
      cervical involvement were significantly higher in the group of UPSC (p = 0.02 and
      p = 0.02, respectively). Significantly more patients with UPSC were treated with
      adjuvant therapy (p = 0.01). No significant difference between the two study
      groups was observed comparing the recurrence rate, the recurrence free interval
      and the 3-year survival. There was also no significant difference between the
      pure and the mixed type UPSC, considering the clinical features and the follow-up
      data. CONCLUSION: The current study presented no significant difference in the
      outcome of MPD-EEC as compared with the pure and the mixed type UPSC, yet
      prospective studies are needed to evaluate the role of adjuvant therapy in each
      study group.

PMID- 12214729
TI  - Laparoscopic surgery for endometrial cancer: long-term results of a multicentric
      study.
AB  - PURPOSE OF INVESTIGATION: Surgical treatment of endometrial cancer was
      traditionally done by laparotomy, however the laparoscopic approach has gained
      wider acceptance by gynecologic surgeons. The primary aim of the study was to
      report the perioperative and postoperative outcomes of laparoscopic surgery in a
      major group of patients with endometrial cancer. The second aim was to study the
      long-term results of laparoscopic surgery in patients with endometrial cancer.
      MATERIAL AND METHOD: A prospective multicentric study was conducted at three
      oncolaparoscopic centres; 221 women who had undergone laparoscopic (177 women) or
      abdominal (44 women) hysterectomy with bilateral salpingo-oophorectomy and
      lymphadenectomy were included in the study. Women with stage IA, grade I did not
      undergo lymphadenectomy unless they had a high risk histologic tumor type. Lymph
      node dissection was performed in 145 women with disease greater than IA or grades
      other than 1. RESULTS: The mean age and weight were similar in the compared
      laparoscopic and open groups. Perioperative blood loss was comparable in both
      groups (211.2 ml vs 245.7 ml, respectively) without any significant consecutive
      changes in serum hemoglobin values. Although the length of operating time for the
      laparoscopic surgery was significantly longer than the time for the laparotomy
      procedure (163.3 min vs 114.7 min, p < 0.0001), the laparoscopic patients were
      discharged from hospital much earlier at 3.9 days (range 2-16) after the
      laparoscopic procedure compared with 7.3 days (range 5-16) after the abdominal
      procedure (p < 0.0001). The difference in surgical complications between groups
      was statistically insignificant (p = 0.58). Similar long-term results were noted
      in both groups. With a median follow-up of 33.6 months for the laparoscopy group
      and 45.2 months for the open group, there were no significant differences in
      tumor recurrence (p = 0.99] or recurrence-free survival (p = 0.86) between the
      two groups. CONCLUSION: The study illustrates that laparoscopically assisted
      surgical staging of endometrial cancer is safe as an open procedure. The
      laparoscopic approach may also be considered for endometrial malignancy which
      typically occurs in obese and elderly, high-risk women. Our analysis showed no
      difference with respect to recurrence or survival between the compared
      laparoscopic and the open group.

PMID- 12214730
TI  - Content of folic acid and free homocysteine in blood serum of human
      papillomavirus-infected women with cervical dysplasia.
AB  - The authors estimated the concentrations of folic acid and free homocysteine in
      the blood serum of women with CIN III (cervical intraepithelial neoplasia
      Burghard's classification) infected with DNA HPV (human papillomaviruses) of type
      16 and/or 18. The control group consisted of 49 patients with normal cytological
      smears without HPV infection. Types 16 and/or 18 DNA HPV were found in 50
      patients. This women qualified for the studied group. The sequence of DNA HPV
      type 16 and/or 18 was identified with the PCR method (polymerase chain reaction).
      The high-performance liquid chromatography (HPLC) method was employed to evaluate
      the levels of folic acid and free homocysteine in the blood serum of the examined
      patients. Significantly lower levels of folic acid and higher levels of free
      homocysteine were observed in the blood serum of HPV-positive patients with CIN
      III. The correlation was found between serum concentrations of folic acid and
      free homocysteine in both groups.

PMID- 12214731
TI  - Epidermoid cyst and primary trabecular carcinoid of the ovary: case report.
AB  - In the literature and in our experience epidermoid cysts and carcinoids of the
      ovary are rare benign pathologies which occur more frequently in younger women.
      They probably are a one-sided development of a teratoma, which arise from germ
      cells after the first meiotic division due to either a meiosis I or a meiosis II
      non dysjunction. Diagnosis is possible only with histological examination and
      immunohistochemistry which allow us to differentiate carcinoids from sex-cord
      tumors and ependymomas. Prognosis is very good because the rate of malignant
      transformation is 1.4%-2% and the rate of complications is 14%. Thus conservative
      surgical therapy associated with long-term follow-up is the treatment of choice.

PMID- 12214732
TI  - An observational study of women with positive HPV-DNA tests and normal cytology
      and colposcopy.
AB  - PURPOSE: High risk human papillomaviruses (HPV) are implicated in the aetiology
      of malignant cervical disease. The usefulness of HPV DNA tests in identifying
      women at risk of cervical cancer as an adjunct to cervical cytology is under
      evaluation. PATIENTS AND METHODS: This is a retrospective analysis of 47 women
      positive for high risk HPV but with negative cytology and negative colposcopy at
      the start of the study. Women were observed for three years or more (in 96%
      cases) using six-monthly combined HPV DNA tests, cytological and colposcopic
      evaluation. RESULTS: At the end of follow-up, 29/47 (62%) women were still
      positive for high risk HPV, 45/47 (96%) women had normal cytology and 47/47
      (100%) women continued to have normal colposcopy. CONCLUSIONS: Normal colposcopy
      has an excellent negative predictive value for HPV positive women with normal
      cytology. These women can be safely screened cytologically on a three-yearly
      basis.

PMID- 12214733
TI  - Melanocytic dysplasia and multiple melanoma of the vulva.
AB  - We report a case of a 24-year-old woman with multiple pigmented lesions on her
      vulva. Histologically the lesions showed a heterogeneous pattern: the majority
      consisted of melanoma in situ and invasive melanoma; in a few lesions a much less
      clear-cut picture was found with only melanocytic dysplasia of various degrees.
      Our case shows the relationship between anomalous melanocytic proliferation of
      the vulva and vulvar melanoma and underlines the necessity of a thorough check of
      all melanocytic vulvar lesions also in young patients.

PMID- 12214735
TI  - Five-year survival of a patient with primary endometrial squamous cell carcinoma:
      a case report and review of the literature.
AB  - Primary endometrial squamous cell carcinoma (PESCC) is an uncommon entity, with
      fewer than 100 cases reported in the English literature. Survival data for PESCC
      are not well reported and a precise five-year survival rate for PESCC has not
      been determined. This study focuses on the five-year survival of a 61-year-old
      patient with PESCC and adds information to an area which is not well documented.
      The patient was treated by hysterectomy with bilateral salpingo-oophorectomy and
      assigned to FIGO stage lb. No adjuvant therapy was given. During the 60-month
      follow-up period, the patient remained free of disease. This outcome suggests
      that in the early stage of PESCC, surgical treatment alone is adequate to arrest
      the disease.

PMID- 12214734
TI  - Bleeding from endometrial and vaginal malignant tumors treated with activated
      recombinant factor VII.
AB  - The authors report two cases of successful employment of human recombinant
      activated factor VII in gynecological oncological patients (endometrial cancer
      and vaginal sarcoma) without pre-existing coagulopathy. They conclude that
      recombinant factor VIIa may be an important and effective drug in severe bleeding
      in gynecological oncology.

PMID- 12214736
TI  - Brain metastasis of ovarian cancer after negative second-look laparotomy.
AB  - We present a case of ovarian carcinoma that had brain metastasis seven months
      after having a negative second-look laparotomy and 13 months after the onset of
      diagnosis. Despite intense multidisciplinary treatment with surgery, chemotherapy
      and radiotherapy, the patient died seven months after second-look laparotomy.

PMID- 12214737
TI  - Granular cell tumor of the breast: a rare lesion resembling breast cancer.
AB  - Granular cell tumor (GCT) is an uncommon, usually benign tumor that occasionally
      involves the breast. It is possibly of neural origin (Schwann cells) and usually
      occurs in premenopausal black women. Physical examination, mammographic,
      ultrasonographic findings and pathologic examination may suggest breast
      malignancy. Positive immunohistochemical staining of the cells for S-100 protein,
      NSE, and CEA is indicative of GCT. Surgical treatment of choice is wide local
      excision. We report a case of granular cell tumor of a female breast. A 52-yr-old
      white woman had a palpable mass close to her right axilla. Computer tomography
      (CT) showed a 3.74 cm mass in the mammary tail of Spencer. The findings were
      suspicious for malignancy and the lesion was widely resected. Pathologic
      examination showed granular cell tumor.

PMID- 12214738
TI  - Hypersensitivity reaction to carboplatin: successful resolution by replacement
      with cisplatin.
AB  - Hypersensitivity reactions caused by carboplatin rarely occur. These reactions
      can cause lethal complications and make subsequent therapeutic approaches
      difficult. To date, only a few cases of successful resolution of hypersensitivity
      by replacement of carboplatin with cisplatin have been reported. We report on a
      patient with serous papillary extra-ovarian peritoneal carcinoma who developed a
      hypersensitivity reaction after the 10th weekly administration of carboplatin.
      Two weeks after reaction, intradermal skin testing with paclitaxel, carboplatin,
      cisplatin, and mannitol showed intense reaction only to carboplatin. On the basis
      of these results, the patient was changed to a chemotherapy with cisplatin and
      paclitaxel. A further eight courses of chemotherapy were administered without
      evidence of hypersensitivity reactions. Carboplatin seems to be successfully
      replaceable by cisplatin in case of hypersensitivity reactions.

PMID- 12214739
TI  - Multidrug resistance gene-1 (Pgp) expression in epithelial ovarian malignancies.
AB  - OBJECTIVE: To assess the value of P-glycoprotein (Pgp) expression in advanced
      epithelial ovarian cancer with regard to clinicopathological findings and disease
      prognosis. METHODS: Twenty-four cases diagnosed as primary epithelial ovarian
      malignancies, between 1993-1999, were enrolled in this study. All of the cases
      had undergone cytoreductive surgery and an optimal staging procedure. Following
      cytoreductive surgery, in 18 patients, cisplatin+cyclophosphamide, and in six
      patients, cisplatin+paclitaxel combination chemotherapy regimens were initiated.
      After six courses of chemotherapy, cases were evaluated by pelvic examination,
      transvaginal ultrasound, pelvi-abdominal tomography and serum Ca-125 levels for
      the presence of residual disease. Following this evaluation residual tumor was
      detected in 14 cases and secondary cytoreductive surgery was undergone. In ten
      cases without any clinical and laboratory confirmation of the presence of tumor,
      second-look laparotomy was performed. In 24 epithelial ovarian cancer cases, both
      in primary or secondary cytoreductive surgery, Pgp expression was determined by
      immunohistochemical methods. RESULTS: Following primary surgery, in 25% (6/24) of
      cases, analysis of tumor specimens showed presence of Pgp expression. In cases
      recurring after first-line chemotherapy, Pgp expression was not statistically
      different in regard to chemotherapy regimen (p = 0.098). Pgp expression in
      tumoral tissues after chemotherapy did show a higher Pgp expression than before
      chemotherapy (p = 0.016). No significant correlation was relevant between Pgp
      expression and Ca-125 levels, histopathological differentiation, histologic
      subgroups of tumor, primary and residual tumor sizes and overall survival.
      CONCLUSION: In epithelial ovarian cancer, Pgp expression has no effect on overall
      disease survival.

PMID- 12214740
TI  - Surgical management of early stage cervical cancer: ten years experience from one
      Greek health region.
AB  - PURPOSE OF INVESTIGATION: Cervical cancer is the second most common malignancy in
      women, in both incidence and mortality. In the present study, we report our
      results of treating 93 consecutive patients with early invasive cervical cancers
      (Stages I-IIA). METHODS: The patients of this study comprised all women
      recognized with stage I-IIA cervical cancer during 1991-2000. Patients with stage
      IA1 cervical cancer without lymphvascular space involvement underwent either
      conservative management by means of large loop conization or simple hysterectomy.
      The remaining patients underwent radical hysterectomy and lymphadenectomy or
      radiation therapy. Mean (+/- SD) duration of follow-up was 6 (+/- 1.7) years.
      RESULTS: The mean (+/- SD) age of patients with stage I-IIA cervical cancer was
      41.3 (+/- 9.1) year. Thirty-five patients with stage [A1 disease were managed
      conservatively with loop excision and 19 patients subsequently became pregnant.
      Fifty-two patients with stage IA2, IB and IIA cervical carcinoma underwent
      radical hysterectomy and lymphadenectomy. CONCLUSION: Young women with stage IA1
      cervical carcinoma wishing future fertility who undergo loop excision have a 100%
      cure rate. Women with stage IA2, IB, and IIA cervical cancer should undergo
      radical hysterectomy and lymphadenectomy or radiation therapy.

PMID- 12214741
TI  - Ovarian fibrosarcoma with five-year survival: a case report.
AB  - A 45-year-old postmenopausal woman, Gravida6, Para4, Abortus0, Dilatation x
      Curhetage2, came to the gynaecology department with pelvic pain. The tumor had
      arisen in the right ovary and measured 15 x 12 x 7 cm. Its cut surface varied
      from grey-white with a whorled appearance and showed areas of haemorrhage.
      Histologically the tumor was densely cellular, composed of spindle cells,
      diffusely involved the entire ovarian stroma with no normal ovarian structures
      remaining. Tumor cells had hyperchromatic nuclei with prominent nucleoli. There
      was moderate pleomorphism and the number of mitotic figures was an average of 6
      per 10 high power fields. In the immunohistochemical study, the tumor was
      negative for desmin, muscle-specific actin, estrogen, progesterone receptors and
      CD31, but was positive for vimentin. A low proliferation index with Ki-67 was
      determined. The patient has shown no evidence of recurrent disease for five
      years.

PMID- 12214742
TI  - Second-line with paclitaxel and carboplatin for recurrent disease following first
      paclitaxel and platinum compounds in ovarian carcinoma.
AB  - OBJECTIVE: The combination of paclitaxel and platinum compounds is considered the
      best first-line regimen for advanced ovarian carcinoma. The purpose of this study
      was to evaluate a paclitaxel and carboplatin combination in pretreated patients
      who recurred within 24 months after a complete clinical response with the same
      regimen used as first-line chemotherapy. METHODS: 18 patients were included in
      this study. Second-line chemotherapy consisted of paclitaxel, 175 mg/m2 as a 3
      hour infusion, and carboplatin AUC 6 every 21 days. RESULTS: Among 15 evaluable
      patients, eight (53%) complete and five (34%) partial responses were observed,
      while two (13%) patients had stable disease (SD). The response rate was 67% among
      patients with measurable disease and 52% for evaluable disease. The median
      progression-free interval after second-line chemotherapy was 8.3 months. The
      median progression-free interval for patients with measurable disease was 8.6
      months and for evaluable disease it was 7.9 months. Seven (46%) of 15 patients
      have developed recurrence after second-line chemotherapy with paclitaxel and
      carboplatin with a median time to recurrence of 9.8 months. CONCLUSION:
      Paclitaxel 175 mg/m2 and carboplatin AUC 6 as second-line chemotherapy in this
      sensitive population is effective in terms of response rate and progression-free
      interval.

PMID- 12214743
TI  - Breast-like cancer of the vulva: primary or metastatic? A case report and review
      of the literature.
AB  - A 45-year-old white female presented a polypoid nodule in the vulva, one year
      after she was operated on for breast cancer. Histologic examination showed a
      poorly differentiated carcinoma that closely resembled the primary breast tumor.
      Eight similar cases have been previously described in the literature. This very
      rare event should be differentiated from primary adenocarcinoma of the mammary
      like glands of the vulva. The recognition of such a lesion as primary or
      metastatic is very important, since it greatly influences management and
      prognosis.

PMID- 12214744
TI  - Endometriosis causing extensive intestinal obstruction simulating carcinoma of
      the sigmoid colon: a case report and review of the literature.
AB  - Endometriosis with intestinal serosal involvement is not uncommon in women of
      childbearing age, however, presentation as colon obstruction is rare. Lack of
      pathognomonic symptoms makes diagnosis difficult, the main problem being
      differential diagnosis with neoplasm, even intraoperatively. Reported here is a
      case of extensive bowel obstruction due to sigmoid colon endometriosis in a 43
      year-old woman who presented with signs and symptoms of bowel obstruction. Barium
      enema showed sigmoid obstruction; subsequent exploratory laparotomy showed the
      sigmoid colon surrounded by fibrous tissue, leading to its angulation and
      extensive lumen obstruction. Left oophorectomy and radical resection of
      descending and sigmoid colon as for bowel carcinoma were successfully employed.
      Pathological examination revealed endometriosis in the bowel wall with
      preservation of the mucosa. Aetiology, clinical presentation, differential
      diagnosis and therapeutic options for intestinal obstruction due to endometriosis
      are discussed.

PMID- 12214745
TI  - The role of the mode of delivery in the alteration of intrapartum pathological
      cervical cytologic findings during the postpartum period.
AB  - OBJECTIVE: The aim of the study was to determine whether abnormal antepartum
      cervical cytologic findings change in the postpartum period and the relation of
      this alteration to the mode of delivery. STUDY DESIGN: Between 1991 and 2000, 192
      pregnant women with antepartum abnormal cervical cytology were identified;
      complete demographic, clinical and cytologic reports were available for 90 of
      them. Papanicolaou smear tests were collected and separated in three groups using
      the Bethesda classification system (ASCUS, L-SIL and H-SIL). RESULTS: Of the 90
      women, 52 (61.1%) were delivered vaginally and 38 (38.9%) by cesarean section. No
      difference was found between women delivered vaginally and those delivered by
      cesarean section, regardin age, parity and smoking history. The overall
      postpartum regression rate for the 20 women with antepartum H-SIL cells was 45%.
      Of the 12 women with H-SIL cells who were delivered vaginally, eight (66.6%)
      showed regression in the postpartum period while this regression was achieved
      only in one (12.5%) woman, who was delivered by cesarean section (p < 0.002).
      CONCLUSION: Postpartum spontaneous regression of suspicious Papanicolaou smears
      consistent with H-SIL occurs with increased frequency among women who are
      delivered vaginally compared to those delivered by cesarean section.

PMID- 12214746
TI  - Hydatidiform mole at extreme ages of reproductive life in a developing country
      from 1932 to 2000.
AB  - PURPOSE OF INVESTIGATION: To determine the rates of hydatidiform mole (HM) cases
      at extreme reproductive life in a developing country. METHODS: A descriptive
      study was performed to assess the number of pregnancies and deliveries in Turkey,
      from 1932 to 2000, based on nationally or internationally published data from
      different university and state maternity hospitals. RESULTS: A spectrum of
      prevalence rates in different hospitals were depicted. Almost all of represented
      data were hospital-based. Percentages of all HM cases < 19 years old and > 40
      years old compared to the total number of HMs in each study were not mentioned.
      In addition, the number of HM compared to total number of deliveries and
      pregnancies in those age groups were not provided in those studies. CONCLUSION:
      There appears to be a need for further descriptive studies on a national basis,
      in regard to assess total number of HM cases per total pregnancies and deliveries
      for those age groups.

PMID- 12214747
TI  - Is it now time to evaluate the true accuracy of cervical cytology screening? A
      review of the literature.
AB  - The incidence of and mortality from cervical invasive carcinoma have decreased
      over the last 30 years in the developed world, a fact which has been attributed
      mainly to the implementation of cervical cytology screening programmes
      (Papanicolaou test). The accuracy of this screening has been questioned because
      of false negative reports, thus other technologies have been proposed. There are
      only 12 studies evaluating cytology screening in low prevalence populations. In
      these studies the specificity appears to be high (85-100%) but the sensitivity
      estimates are variable and generally much lower (22-99%). Sensitivity is
      increased if lower thresholds of disease are used. Sampling or laboratory errors
      are important causes of false negative reports. Cytological cervical screening
      does not demonstrate the characteristics of an optimal screening test since it is
      relatively insensitive to the presence of disease although highly specific. The
      true screening accuracy of cytology needs to be assessed so that we can introduce
      strategies to improve smear taking and interpretation.

PMID- 12214748
TI  - Absence of bacterial growth in the culture from the epidural catheter of a
      patient with endometrial carcinoma and febrile neutropenia: a case report and
      review of the literature.
AB  - Infection is a potentially serious complication of long-term epidural (EP)
      catheterization in cancer patients. Although the use of epidural opioid analgesia
      is an effective and safe means for pain relief in terminally ill patients, these
      patients are in need of monitorization for possible infection. This is the first
      report in which EP catheter cultivation has been assessed in an immunocompromised
      and febrile neutropenic endometrial cancer patient.

PMID- 12214749
TI  - Mortality salience and the spreading activation of worldview-relevant constructs:
      exploring the cognitive architecture of terror management.
AB  - Seven experiments assessed the hypothesis derived from terror management theory
      that reminding people of their mortality would increase accessibility of
      constructs central to their worldview. Experiment 1 found that mortality primes,
      relative to control primes, increased accessibility of nationalistic constructs
      for men but not for women. Experiment 2 replicated this finding and also found
      that mortality salience increased romantic accessibility for women but not for
      men. Four subsequent experiments supported the role of unconscious death-related
      ideation in producing these effects. A final experiment demonstrated that
      situational primes can increase the accessibility of nationalistic constructs for
      women after mortality salience. The roles of situational cues and individual
      differences in the effects of exposure to death-related stimuli on worldview
      relevant construct accessibility are discussed.

PMID- 12214750
TI  - Two routes to remembering (and another to remembering not).
AB  - In this article, the author presents evidence about 2 mechanisms of remembering
      that occur when target stimuli are presented in meaningful contexts. One occurs
      when the context has been seen previously; the other occurs when the context is
      new in the test. Both appear to result from the construction of expectations and
      evaluation of outcomes, but the former appears to depend on the formation of
      definite expectations, whereas the latter appears to depend on indefinite
      expectations. These 2 routes to remembering are affected by different factors and
      cause dissociated patterns of remembering. They also have differential
      significance for claims of clear recall versus a feeling of familiarity. The
      results are discussed in terms of the SCAPE framework of memory.

PMID- 12214751
TI  - Is study time allocated selectively to a region of proximal learning?
AB  - Five experiments investigated whether people allocate their study time according
      to the discrepancy reduction model (i.e., to the most difficult items; J.
      Dunlosky & C. Hertzog, 1998) or to items in their own region of proximal
      learning. Consistent with the latter hypothesis, as more time was given, people
      shifted toward studying more difficult items. Experts, whether college students
      or Grade 6 children, devoted their time to items that were more difficult than
      did novices. However, in a multiple-trials experiment, people regressed toward
      easier items on Trial 2 rather than shifting to more difficult items, perhaps
      because Trial 1 feedback revealed poor learning of the easiest items. These
      findings are in opposition to the discrepancy reduction model and support the
      region of proximal learning hypothesis.

PMID- 12214752
TI  - Time-dependent gambling: odds now, money later.
AB  - Four experiments investigated temporal changes in the influence of probability
      and payoffs on gambling. Using urn draws, the authors found in Experiment I that
      temporal distance increased the influence of payoffs and decreased the influence
      of probability on preferences. The authors found in Experiment 2 that in choosing
      among the more distant gambles, participants offered more reasons dealing with
      payoffs and fewer reasons dealing with probability. In Experiments 3 and 4, the
      authors extended the scope of these findings using a card game and a raffle. The
      results were interpreted in terms of a temporal construal process that highlights
      the desirability of outcomes in the distant future and the feasibility of
      attaining the outcomes in the near future.

PMID- 12214753
TI  - When language affects cognition and when it does not: an analysis of grammatical
      gender and classification.
AB  - The focus of this work was on the relation between grammatical gender and
      categorization. In one set of studies, monolingual English-, Spanish-, French-,
      and German-speaking children and adults assigned male and female voices to
      inanimate objects. Results from Spanish and French speakers indicated effects of
      grammatical gender on classification; results from German speakers did not. A
      connectionist model simulated the contradicting findings. The connectionist
      networks were also used to investigate which aspect of grammatical gender was
      responsible for the different pattern of findings. The predictions from the
      connectionist simulations were supported by the results from an artificial
      language-learning task. The results from this work demonstrate how connectionist
      networks can be used to identify the differences between languages that affect
      categorization.

PMID- 12214754
TI  - Dominance of global visual properties at birth.
AB  - Six experiments are reported that were aimed at demonstrating the presence in
      newborns of a perceptual dominance of global over local visual information in
      hierarchical patterns, similar to that observed in adults (D. Navon, 1977, 1981).
      The first four experiments showed that, even though both levels of visual
      information were detectable by the newborn (Experiments 1A and 1B), global cues
      enjoyed some advantage over local cues (Experiments 2 and 3). Experiments 4A and
      4B demonstrated that the global bias was strictly dependent on the low spatial
      frequency content of the stimuli and vanished after selective removal of low
      spatial frequencies. The results are interpreted as suggesting parallels between
      newborns' visual processing and processing later in development.

PMID- 12214756
TI  - What very small numbers mean.
AB  - This article presents a theoretical and experimental framework for assessing the
      biases associated with the interpretation of numbers. This framework consists of
      having participants convert between different representations of quantities.
      These representations should include both variations in numerical labels that
      symbolize quantities and variations in displays in which quantity is inherent.
      Five experiments assessed how people convert between relative frequencies,
      decimals, and displays of dots that denote very low proportions (i.e.,
      proportions below 1%). The participants demonstrated perceptual, response, and
      numerical transformation biases. Furthermore, the data suggest that relative
      frequencies and decimals are associated with different abstract representations
      of amount.

PMID- 12214755
TI  - Grip morphology and hand use in chimpanzees (Pan troglodytes): evidence of a left
      hemisphere specialization in motor skill.
AB  - Three experiments on grip morphology and hand use were conducted in a sample of
      chimpanzees. In Experiment 1, grip morphology when grasping food items was
      recorded, and it was found that subjects who adopted a precision grip were more
      right-handed than chimpanzees using other grips. In Experiment 2, the effect of
      food type on grasping was assessed. Smaller food items elicited significantly
      more precision grips for the right hand. In Experiment 3, error rates in grasping
      foods were compared between the left and right hands. Significantly more errors
      were made for the left compared with the right hand. The cumulative results
      indicate that chimpanzees show a left-hemisphere asymmetry in motor skill that is
      associated with the use of precision grips.

PMID- 12214757
TI  - On-line, simultaneous quantification of ethanol, some metabolites and water
      vapour in breath following the ingestion of alcohol.
AB  - Selected ion flow tube mass spectrometry, SIFT-MS, has been used to measure
      simultaneously the concentrations in exhaled breath of ethanol, acetaldehyde,
      ammonia, acetone and, routinely, water vapour, following the ingestion of various
      amounts of ethanol in 500 ml of water. These breath analyses were obtained from
      only single exhalations, the results being available immediately in real time.
      The breath ethanol reaches concentrations that are only approximately consistent
      with its dilution in blood and body water. For moderate ethanol doses the decay
      quickly exhibits first-order kinetics (a single exponential decay) whereas for
      relatively large ethanol doses, the initial decay of ethanol from the breath is
      slow, indicating saturation kinetics. For smaller doses, and following a meal,
      the breath ethanol increases only slightly indicating that it is largely
      metabolized in the stomach. We suggest that the time delay (following ethanol
      ingestion) before the breath ethanol begins to increase is an indicator of the
      gastric emptying rate. Then the rate of decay of ethanol from the breath/blood is
      related to its rate of metabolism subsequent to its dispersal into the body
      water. The much lower breath acetaldehyde levels correlate well with the ethanol
      levels indicating that it is mostly formed from the metabolism of the ethanol.
      The breath ammonia is seen to 'dip' following the water/alcohol drink and this is
      consistent with previous work in which this same phenomenon was observed
      following the ingestion of comparable volumes of liquid meals. The simultaneous
      breath acetone concentrations increase somewhat with time as is expected during
      the fasting state. The water vapour measurements are indicators of the precision
      and accuracy of the breath analyses, these being sufficient to show the
      differences between the breath (body) temperatures of the individuals of less
      than 1 degrees C. This study demonstrates the potential of SIFT-MS for non
      invasive physiological measurement.

PMID- 12214758
TI  - Novel mechano-acoustic technique and instrument for diagnosis of cartilage
      degeneration.
AB  - Fibrillation of articular surface and depletion of proteoglycans are the
      structural changes related to early osteoarthrosis. These changes make cartilage
      softer and prone to further degeneration. The aim of the present study was to
      combine mechanical and acoustic measurements towards quantitative arthroscopic
      evaluation of cartilage quality. The performance of the novel ultrasound
      indentation instrument was tested with elastomers and bovine articular cartilage
      in vitro. The instrument was capable of measuring elastomer thickness (r = 1.000,
      p < 0.01, n = 8) and dynamic modulus (r = 0.994, p < 0.01, n = 13) reliably.
      Osteochondral plugs were tested before and after enzymatic degradation of
      cartilage proteoglycans by trypsin or chondroitinase ABC, and of cartilage
      collagens by collagenase. Trypsin and collagenase induced a mean decrease of 
      31.2 +/- 12.3% (+/- SD, p < 0.05) and -22.9 +/- 20.8% (p = 0.08) in dynamic
      modulus, respectively. Rate of cartilage deformation, i.e. creep rate, increased
      by +117.8 +/- 71.4% (p < 0.05) and +24.7 +/- 35.1% (p = 0.17) in trypsin and
      chondroitinase ABC treatments, respectively. Collagenase induced a greater
      decrease in the ultrasound reflection from the cartilage surface (-54.2 +/-
      29.6%, p < 0.05) than trypsin (-17.1 +/- 13.5%, p = 0.08). In conclusion,
      combined quantitation of tissue modulus, viscoelasticity and ultrasound
      reflection from the cartilage surface provides a sensitive method to distinguish
      between normal and degenerated cartilage, and even to discern proteoglycan loss
      and collagen degradation from each other.

PMID- 12214759
TI  - Non-invasive gastric motility monitor: fast electrogastrogram (fEGG).
AB  - We propose a new analysis method to extract the motility information from the
      electrogastrogram signal that has been recorded at a higher sampler rate than the
      conventional approaches. This technique utilizes a fourth order Butterworth
      bandpass filter in extracting the 50-80 cycles per minute (cpm) activity that was
      previously noted to represent the spike activity range of the cutaneous signals
      of dogs. Receiver operating characteristics (ROC) analyses have been applied to
      the processed data to compare the detection performance of our fEGG technique to
      the conventional approaches that use the slow wave as the reference. The areas
      under the ROC curves comparing the changes from postprandial stage to fed stage
      for the fEGG study was found to be 0.961 while for the slow wave it was 0.686. We
      offer our method as a complementary one to the existing methods.

PMID- 12214760
TI  - In vivo measurement of human skin absorption of topically applied substances by a
      photoacoustic technique.
AB  - A photoacoustic technique is used for studying topically applied substance
      absorption in human skin. The proposed method utilizes a double-chamber PA cell.
      The absorption determination was obtained through the measurement of the thermal
      effusivity of the binary system substance-skin. The theoretical model assumes
      that the effective thermal effusivity of the binary system corresponds to that of
      a two-phase system. Experimental applications of the method employed different
      substances of topical application in different parts of the body of a volunteer.
      The method is demonstrated to be an easily used non-invasive technique for
      dermatology research. The relative concentrations as a function of time of
      substances such as ketoconazol and sunscreen were determined by fitting a
      sigmoidal function to the data, while an exponential function corresponds to the
      best fit for the set of data for nitrofurazona, vaseline and vaporub. The time
      constants associated with the rates of absorption, were found to vary in the
      range between 10 and 58 min, depending on the substance and the part of the body.

PMID- 12214761
TI  - Investigation of oesophageal photoplethysmographic signals and blood oxygen
      saturation measurements in cardiothoracic surgery patients.
AB  - Pulse oximeter probes attached to the finger may fail to estimate blood oxygen
      saturation (SpO2) in patients with compromised peripheral perfusion (e.g.
      hypothermic cardiopulmonary bypass surgery). The measurement of SpO2 from a
      central organ such as the oesophagus is suggested as an alternative to overcome
      this problem. A reflectance oesophageal pulse oximeter probe and a processing
      system implemented in LabVIEW were developed. The system was evaluated in
      clinical measurements on 50 cardiothoracic surgery patients. Oesophageal
      photoplethysmographic (PPG) signals with large amplitudes and high signal-to
      noise ratios were measured from various depths within the oesophagus from all the
      cardiothoracic patients. The oesophageal PPG amplitudes from these patients were
      in good agreement with previous oesophageal PPG amplitude measurements from
      healthy anaesthetized patients. The oesophageal pulse oximeter SpO2 results
      agreed well with the estimated arterial oxygen saturation (SaO2) values inferred
      from the oxygen tension obtained by blood gas analysis. The mean (+/- SD) of the
      differences between the oesophageal pulse oximeter SpO2 readings and those from
      blood gas analysis was 0.02 +/- 0.88%. Also, the oesophageal pulse oximeter was
      found to be reliable and accurate in five cases of poor peripheral perfusion when
      a commercial finger pulse oximeter probe failed to estimate oxygen saturation
      values for at least 10 min. These results suggest that the arterial blood
      circulation to the oesophagus is less subject to vasoconstriction and decreased
      PPG amplitudes than are the peripheral sites used for pulse oximetry such as the
      finger. It is concluded that oesophageal SPO2 monitoring may be of clinical
      value.

PMID- 12214762
TI  - Dielectric properties of blood: an investigation of temperature dependence.
AB  - We have investigated the temperature dependence of the electrical parameters
      (permittivity and conductivity) of blood. The measuring system, composed of an
      impedancemeter (HP 4291 A), an open-ended coaxial line and a temperature
      controlling set, was designed for dielectric measurement in the frequency range
      of 1 MHz to 1 GHz. Measurements were performed on ex vivo blood of humans and
      animals (cow and sheep). The results obtained show the weak sensibility and a
      change of sign of the temperature coefficient of the relative permittivity (about
      0.3% degrees C(-1) at 1 MHz and -0.3% degrees C(-1) at 1 GHz). The conductivity
      presents a more significant variation (of the order of 1% degrees C(-1) over the
      whole operating frequency range.

PMID- 12214763
TI  - In vitro investigation of calcium distribution and tissue thickness in the human
      thoracic aorta.
AB  - Atherosclerosis represents a significant cause of morbidity and mortality in the
      western world. Manifestations of atherosclerotic disease among the elderly
      include the development of raised lesions that often include calcified regions
      with material properties similar to bone. There is little information available
      about the amount and distribution of these calcified plaques within the human
      aorta, partly due to the difficulty in obtaining this information during in vivo
      studies. We report the results of a cadaveric investigation of thoracic aortic
      wall thickness, diameter and calcium content. A non-destructive x-ray imaging
      technique was used to obtain two-dimensional maps of total thickness and mineral
      content in excised thoracic aortic specimens. In a study of 39 individuals (23
      male and 16 female, aged 20-92 years) we report a significant non-linear
      correlation between calcium burden and age, with calcium deposition most commonly
      occurring proximal to the ostia of major branching vessels. We also found a
      significant linear correlation between age and both total aortic wall thickness
      and aortic diameter. An improved understanding of the pathological changes in the
      ageing thoracic aorta may be useful in the development of strategies to reduce
      the undesirable vessel calcification associated with atherosclerosis.

PMID- 12214764
TI  - Noninvasive quantification of respiratory modulation on left ventricular size and
      stroke volume.
AB  - To noninvasively explore the complex interactions between heart rate, left
      ventricular (LV) stroke volume (SV) and respiration, different techniques were
      proposed and applied to the beat-to-beat measurements of end-diastolic (ED), end
      systolic (ES) volumes and SV, obtained from echocardiographic acoustic
      quantification LV volume signal. Data were obtained from eight patients with
      dilated cardiomyopathy (DCM, age 60 +/- 2, mean +/- SE), and from 11 age-matched
      healthy volunteers (N, age 63 +/- 2). Spectral analysis showed an increase in HF
      power in DCM, both in ED (in ml2, 58 +/- 18 versus 19 +/- 5 in N) and in SV (in
      ml2, 55 +/- 12 versus 17 +/- 5 in N), together with an increase in total power
      (in ml2, ED: 119 +/- 31 in DCM versus 48 +/- 9 in N; SV: 88 +/- 17 in DCM versus
      31 +/- 8 in N). Folded scattergrams evidenced higher amplitude oscillations in
      DCM (in ml, ES: 7.93 +/- 1.29; ED: 7.94 +/- 1.59; SV: 7.27 +/- 0.91) compared to
      N (in ml, ES: 4.08 +/- 0.64; ED: 3.56 +/- 0.65; SV: 3.63 +/- 0.43). Moreover, the
      prevalent effect of increased afterload generating SV reduction during
      inspiration was pointed out in N, while an intersubject dispersion in the
      relation between respiratory phase and LV dimension changes was found in DCM.
      Black-box model identification summarized these mechanisms by means of a few
      quantitative parameters.

PMID- 12214765
TI  - Validation of a device to measure arterial pulse wave velocity by a
      photoplethysmographic method.
AB  - We aimed to validate a new method for measuring arterial pulsewave transit time
      and pulsewave velocity (a measure of arterial elasticity), based on the principle
      of photoplethysmography (PPG), and to compare transcutaneous values with those
      obtained by intra-arterial measurements. Three validation experiments are
      described. (a) PPG pulse wave delay times (defined as the time interval between
      the ECG R wave and the foot of the arterial pulse wave measured at the wrist or
      ankle) were compared to values obtained simultaneously from an established
      methodology (Doppler ultrasound). (b) Aortic pulsewave delay times in 17 subjects
      obtained non-invasively by the PPG method were compared with those obtained from
      the intra-arterial pressure wave. (c) Repeatability measurements of PWV on the
      same subjects were carried out over two timescales (minutes and hours) in the
      arm, the leg and the trunk. The Doppler and PPG delay times correlated well, as
      did intra-arterial and transcutaneous values. Repeatability at short timescales
      was good (coefficients of variation (CV) < 6% for all measurement sites) and, at
      the longer timescale, was satisfactory (CVs in the aorta, the arm and leg were
      6.3, 13.1 and 16.0, respectively). The PWV values agreed well with others in the
      literature. We conclude that the PPG technique provides a complement to existing
      methods for the non-invasive measurement of arterial compliance. Its simplicity
      and ease of use make it suitable for large-scale epidemiological studies.

PMID- 12214766
TI  - Analysis of the photoplethysmographic signal by means of the decomposition in
      principal components.
AB  - We study the plethysmographic signal using principal component analysis (PCA). By
      decomposing the signal using this method, we are able to regenerate it again,
      preserving in the process the functional relationships between the components. We
      have also found the relative contributions of each specific component to the
      signal. First return maps have been made for the series of residues of the
      decomposition. Further analysis using spectral methods has shown that the
      residues have a 1/f -like structure, which confirms the presence and conservation
      of this component in the signal and its relative independence with respect to the
      oscillating component (Hernandez et al 2000 Rev. Cubana Inform. Medica 1 5). Our
      conclusions are that: (i) PCA is a good method to decompose the plethysmographic
      signal since it preserves the functional relationships in the variables, and this
      could be potentially useful in finding new clinically relevant indices; (ii) the
      1/f process of the plethysmographic signal is preserved in the residues of the
      decomposed signal when PCA is used; (iii) clinically relevant parameters can
      potentially be obtained from photoplethysmographic signals when PCA is used.

PMID- 12214767
TI  - Providing a homogeneous visual field with an integrating sphere.
AB  - Homogeneous visual fields are widely used in visual perception and psychophysical
      studies. An integrating sphere can be guaranteed to provide a homogeneous diffuse
      source of illumination. We report here on a custom built integrating sphere,
      which provides a uniformly illuminated, unpatterned visual field. The apparatus
      allows for superior subject comfort over other methods. Binocular viewing is
      facilitated and the apparatus is highly adaptable to various experimental
      situations requiring a homogeneous visual field.

PMID- 12214768
TI  - Human factors error and patient monitoring.
AB  - A wide range of studies have shown that human factors errors are the major cause
      of critical incidents that threaten patient safety in the medical environments
      where patient monitoring takes place, contributing to approximately 87% of all
      such incidents. Studies have also shown that good cognitively ergonomic design of
      monitoring equipment for use in these environments should reduce the human
      factors errors associated with the information they provide. The purpose of this
      review is to consider the current state of knowledge concerning human factors
      engineering in its application to patient monitoring. It considers the prevalence
      of human factors error, principles of good human factors design, the effect of
      specific design features and the problem of the measurement of the effectiveness
      of designs in reducing human factors error. The conclusion of the review is that
      whilst the focus of human factors studies has, in recent years, moved from
      instrument design to organizational issues, patient monitor designers still have
      an important contribution to make to improving the safety of the monitored
      patient. Further, whilst better psychological understanding of the causes of
      human factors errors will in future guide better human factors engineering, in
      this area there are still many practical avenues of research that need exploring
      from the current base of understanding.

PMID- 12214769
TI  - Brain development and the ontogeny of developmental disabilities.
AB  - Brain development is an active process that continues throughout life. During the
      past few decades, increased knowledge of this process has led to an improved
      understanding of the causes of its disruption. Complex genetic and molecular
      processes have been identified as components of the sequence of events leading to
      mature brain formation. However, the limitations in our knowledge about brain
      development are still significant. For example, 10% to 20% of persons with severe
      mental retardation of unknown origin appear entirely normal by standard
      neuropathologic studies. In this chapter, we review normal brain development and
      discuss how alterations during this process can lead to developmental
      disabilities. An overview of the most important steps in brain development, the
      basic mechanisms involved, and possible etiologies for the clinical
      manifestations of developmental disabilities is provided. General concepts about
      brain development, timing, and environmental influences are also considered. As
      we learn more about the genetic mechanism and molecular processes underlying
      brain development, we will better understand the ontogeny of various
      developmental disabilities and hopefully improve approaches to prevention and
      treatment.

PMID- 12214770
TI  - Applying CFTR molecular genetics to facilitate the diagnosis of cystic fibrosis
      through screening.

PMID- 12214771
TI  - Celiac disease: extraintestinal manifestations, associated diseases, and
      complications.
AB  - The aim of this chapter is to increase the familiarity of physicians with
      conditions or complications associated with CD, a disease that is more common
      than had been thought in the past. The differentiation between atypical
      manifestations, associated disease, and complications of CD is not always clear.
      With careful adherence to the necessary dietary restrictions, patients with CD
      can remain relatively free of troublesome symptoms, their long-term prognosis is
      excellent, and most complications can be prevented. (24) Indeed, 5-year survival
      rates of patients with CD did not differ from those in the general population.
      (6) This review emphasizes the importance of a screening policy for silent CD,
      justified on the basis of later developing complications such as malignancy,
      development of low bone mineral density, risk of neurologic abnormalities, and
      associated diseases, which may be preventable by GFD.

PMID- 12214772
TI  - Glutamine metabolism in the fetus and critically ill low birth weight neonate.

PMID- 12214773
TI  - Indications for and questions about antenatal steroids.
AB  - Antenatal glucocorticoid treatment of women at risk of preterm delivery between
      24 and 34 weeks' gestation has been the standard of care since 1994. Recent
      information supports its use with preterm prolonged rupture of membranes, in very
      early gestations in which neonatal survival will be attempted, and in women with
      preeclampsia. Many women who deliver before 30 weeks' gestation have chronic
      silent chorioamnionitis, which does not seem to be a contraindication to
      antenatal glucocorticoid therapy. The preferred antenatal treatment is a short-
      and long-acting betamethasone combination given as 12-mg maternal injections at
      the identification of preterm labor and 24 hours later. Repeated courses of
      antenatal glucocorticoids given at 7- to 10-day intervals if preterm delivery
      does not occur are not indicated. Antenatal glucocorticoid therapy is very
      effective, and no adverse effects of a single treatment course have been
      identified.

PMID- 12214774
TI  - Recognition and treatment of endocrine/metabolic emergencies in children: part I.
AB  - A wide variety of endocrine/metabolic emergencies exists that may be isolated
      occurrences, the initial manifestation of an endocrine/metabolic disorder (eg,
      diabetes mellitus or hypoparathyroidism), or an acute abnormality in a child with
      known endocrine/metabolic disease as a result of intercurrent illness, emotional
      stress, or noncompliance with medications. The pediatric emergency medicine
      provider is faced with a difficult task when evaluating a child with a suspected
      endocrine or metabolic disorder, especially the child with no known underlying
      condition, since the signs and symptoms of such disorders are varied and
      nonspecific. This may lead to a delayed or missed diagnosis, and can have serious
      consequences (eg, cerebral dysfunction leading to coma or death as seen in
      diabetic ketoacidosis, hypoglycemia, or adrenal insufficiency). Prompt diagnosis
      depends on the collection of critical and archival laboratory specimens before
      the administration of nonspecific therapy.

PMID- 12214775
TI  - Attainments in atop: special aspects of allergy and IgE.
AB  - Positive skin tests or elevated levels of specific immunoglobulin E (IgE) in the
      serum define IgE sensitization or "atopy." The term "allergy" refers to the
      clinical expression of atopic IgE-mediated disease. Genetic predisposition and
      decreased infections in early childhood, together with exposure and sensitization
      to environmental allergens, fix the basis for the elevation of IgE in infancy.
      Elevated IgE shortly after birth is associated with later onset of allergic
      disorders. IgE participates both in the immediate hypersensitivity response and
      in the induction of chronic allergic inflammation. The allergic response is
      distinct from other immune reactions in its reliance on IgE, its high-affinity
      receptor FcepsilonRI, and the primary effector cell-the tissue mast cell. IgE
      initiates the process of allergic inflammation by binding to FcepsilonRI on
      inflammatory cells in the airways, the gut, and the skin. Cross-linking of the
      IgE molecules bound to FcepsilonRI on the surface of mast cells by allergen
      initiates the early-phase allergic reaction. IgE bound to FcepsilonRI sets off
      the release of inflammatory mediators, including histamine, leukotrienes and
      cytokines, and leads to eosinophilic infiltration and inflammation in the
      affected mucosa or skin. IgE, attached to the low-affinity receptor FcepsilonRII
      on activated B cells and antigen-presenting cells, enhances allergen capture and
      type 2 helper T (Th2) cell activation, and may trigger other immunoregulatory
      pathways. Considerable effort in therapeutic research has focused on interference
      with IgE function because of its position high in the allergic cascade. Therapy
      with anti-IgE is one such approach that shows much promise. Large clinical
      studies of anti-IgE in adults and children have documented its safety and
      effectiveness by demonstrating the reduction of free IgE in circulation,
      inhibition of both early- and late-phase allergic reactions, steroid sparing, and
      protection against exacerbation of asthma and allergic rhinitis.

PMID- 12214776
TI  - Pathophysiology of intestinal food allergy.
AB  - The gastrointestinal tract plays an important role in the mucosal immune
      response. While acting as a conduit allowing the transfer of nutrients from the
      intestinal lumen to the systemic circulation, it also protects against invasion
      by microbes and other antigens by the induction of an immune response. A
      downregulation of these immune responses to nonharmful antigenic substances is
      termed oral tolerance. A breakdown or underdevelopment of oral tolerance may
      therefore lead to the development of food allergy. Adverse immunologic reactions
      to food may be a consequence of both IgE- and non-IgE-mediated mechanisms.
      Although genetic factors play a major role in the development of allergic
      disease, other factors involved in an immature mucosal immune response have been
      implicated. Non-IgE-mediated allergic responses tend to involve a T cell-mediated
      delayed hypersensitivity reaction, and released cytokines act as determinants of
      the immune response. The "hygiene hypothesis" proposes that a reduction in
      infections in early infancy predisposes to allergic responses. Early childhood
      infections promote the induction of a T-helper type 1 response that protects
      against the development of allergy, which is predominantly a T-helper type 2
      response. The role of B cells and T cells in the development of food allergy is
      incompletely under- stood, but advances in the evaluation and characterization of
      food allergens has opened exciting new avenues in this study.

PMID- 12214777
TI  - Immune neutropenia in the neonate.
AB  - Immune-mediated neonatal neutropenias include alloimmune neonatal neutropenia,
      neonatal autoimmune neutropenia, and autoimmune neutropenia of infancy. These
      disorders have remained somewhat nebulous entities with difficulties persisting
      in both clinical identification and laboratory confirmation. A review of these
      disorders is presented, with basic information on the neutrophil antigen systems,
      pathophysiologic mechanisms, laboratory diagnosis, and therapeutic options.

PMID- 12214778
TI  - Primary vesicoureteral reflux in childhood.

PMID- 12214779
TI  - Stem cell bone marrow transplantation in patients with metabolic storage
      diseases.
AB  - In 1984, an initial report was published on the use of BMT for inborn errors of
      metabolism. Our first BMT patient had a diagnosis of Maroteaux-Lamy syndrome. She
      had end-stage cardiopulmonary disease at the time of the transplant and was
      considered likely to die within months. (69) She is still alive 2 decades later,
      albeit with limited pulmonary function. In 1992, experimental data demonstrated
      the prevention of CNS deterioration in fucosidase-deficient dogs after BMT.70
      These findings have been noted in many other similar studies. (46) Ample data
      indicate that BMT can reconstitute the CNS in several of these diseases. Progress
      is continuing in reducing the morbidity and mortality. In the near future,
      additional advances may allow for no loss of life and no illness during the bone
      marrow transplantation process. There is hope that by using neonatal screening
      techniques, infants at risk can have metabolic storage diseases diagnosed before
      the diseases progress so that effective treatment can be provided. The
      combination of all of these advances should result in a logarithmic improvement
      within the next 2 decades. The plan will be to avoid any mortality or morbidity
      and to always provide complete engraftment that is permanent and enters all
      tissues completely.

PMID- 12214780
TI  - Behavioral phenotypes in genetic syndromes: genetic clues to human behavior.
AB  - A behavioral phenotype is the characteristic cognitive, personality, behavioral,
      and psychiatric pattern that typifies a disorder. A number of genetic syndromes
      have been identified as having this type of distinctive and consistent behavior
      pattern. It may act as an important diagnostic sign, like a malformation or
      characteristic facial appearance. Such patterns are also useful for the
      physician's anticipatory guidance from an educational, rehabilitative, and
      parenting perspective. In addition, because they are the consequences of known
      genetic alterations, behavioral phenotypes can be potentially highly valuable
      clues to the identification of genes in the population that are important to
      determination of cognitive skills or deficits, personality determinants,
      behavioral abnormalities, or psychiatric disorders. The nature of a behavioral
      phenotype and its potential for genetic insight can be appreciated through the
      examples of Williams syndrome, Prader-Willi syndrome, and Angelman syndrome. The
      cognitive and behavioral characteristics of these disorders are distinctive.
      Williams syndrome is known for its association with remarkable conversational
      verbal abilities and excessive empathy, whereas Prader-Willi syndrome is known
      for temper tantrums and obsessive-compulsive features, and Angelman syndrome is
      associated with a constantly happy affect and hyperactivity. The genetic basis
      for each of these disorders is known, and the pathophysiology and genotype
      phenotype correlations are beginning to provide insight into genes responsible
      for personality characteristics and behavioral abnormalities.

PMID- 12214781
TI  - Genetics and cardiac arrhythmias.
AB  - In this review, the up-to-date understanding of the molecular basis of primary
      ventricular arrhythmias is outlined. Two disorders have recently been well
      described at the molecular level, the long QT syndromes and Brugada syndrome, and
      we review the current scientific knowledge of each disease. Two other disorders,
      arrhythmogenic right ventricular dysplasia and Wolff-Parkinson-White syndrome,
      which are on the cusp of understanding, are also described.

PMID- 12214782
TI  - Back-neck pain and symptoms of anxiety and depression: a population-based twin
      study.
AB  - BACKGROUND: Clinical and epidemiological studies have shown an association
      between anxiety and depression and pain in the back and neck. The nature of this
      relationship is not clear. This study aimed to investigate the extent to which
      common genetic and environmental aetiological factors contribute to the
      covariance between symptoms of anxiety and depression and back-neck pain.
      METHODS: Measures of back-neck pain and symptoms of anxiety and depression were
      part of a self-report questionnaire sent in 1992 to twins born in Norway between
      1967 and 1974 (3996 pairs). Structural equation modelling was applied to
      determine to what extent back-neck pain and symptoms of anxiety and depression
      share genetic and environmental liability factors. RESULTS: The phenotypic
      correlation between symptoms of anxiety and depression and back-neck pain was
      0.31. Individual differences in both anxiety and depression and back-neck pain
      were best accounted for by additive genetic and individual environmental factors.
      Heritability estimates were 0.53 and 0.30 respectively. For back-neck pain,
      however, a model specifying only shared- and individual environmental effects
      could not be rejected. Bivariate analyses revealed that the correlation between
      back-neck pain and symptoms of anxiety and depression was best explained by
      additive genetic and individual environmental factors. Genetic factors affecting
      both phenotypes accounted for 60% of the covariation. There were no significant
      sex differences. CONCLUSION: The results support previous findings of a moderate
      association between back-neck pain and symptoms of anxiety and depression, and
      suggest that this association is primarily due to common genetic effects.

PMID- 12214783
TI  - Hypothalamic-pituitary-adrenal axis function in patients with chronic depression.
AB  - BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis function in patients with
      chronic depression has previously been shown to be normal when measured using the
      dexamethasone suppression test (DST). We examined patients with chronic
      depression using the sensitive dexamethasone/corticotropin releasing hormone
      (dex/CRH) test and the dexamethasone suppression test (DST) to establish whether
      HPA axis abnormalities are present in this group. We also compared the
      sensitivity of the two tests and compared the results with previous studies in
      depression that have not specifically selected chronic patients. METHOD: Twenty
      nine patients with the chronic subtype of major depressive disorder and 28
      matched controls underwent examination of HPA axis function. RESULTS: Neither the
      cortisol response to the DST or the dex/CRH test differed significantly between
      the patient and control groups. There was a trend in favour of more patients than
      controls having an abnormal response to the dex/CRH test (P = 0.052). Neither the
      patients with an abnormally enhanced response, nor the magnitude of response
      could be predicted by any illness or demographic variable. CONCLUSION: The HPA
      axis is not overtly abnormal in chronic depression. This contrasts with previous
      findings in acute depression and bipolar disorder and may suggest that the HPA
      axis abnormalities present in acute depression resolve, but are not accompanied
      by symptom resolution. Alternatively, a subgroup of depressives with less HPA
      dysfunction may progress to chronicity. This has implications for treatment and
      prognosis. The dex/CRH is a more sensitive test of HPA axis function than the DST
      in patients with chronic depression.

PMID- 12214784
TI  - Decreased cerebral haemodynamic response to cognitive and physiological tasks in
      mood disorders as shown by near-infrared spectroscopy.
AB  - BACKGROUND: Hypofrontality has been demonstrated in mood disorders by functional
      brain imaging methods such as positron emission tomography. However, the
      neurobiological basis of hypofrontality has not been well clarified. Near
      infrared spectroscopy (NIRS) is a non-invasive technique for continuous
      monitoring of alterations in oxygenated (oxyHb) and deoxygenated (deoxyHb)
      haemoglobin using near-infrared light, which penetrates biological tissues.
      METHODS: We used NIRS during cognitive and physiological tasks to investigate
      alterations of haemoglobin oxygenation in the frontal region of euthymic patients
      with mood disorders (major depressive disorder (MD) and bipolar disorder (BP))
      and in controls. RESULTS: The increase of oxyHb during a verbal fluency task was
      significantly less in the MD and the BP groups than in the controls. The MD group
      showed a significantly smaller decrease of oxyHb during hyperventilation than the
      controls. The BP group also showed a similar trend. CONCLUSIONS: These findings
      suggest that the hypofrontality in mood disorders may be associated with a poor
      response in the cerebral blood vessels to neuronal and chemical stimuli.

PMID- 12214785
TI  - Prevention and treatment of post-partum depression: a controlled randomized study
      on women at risk.
AB  - BACKGROUND: Research is needed to evaluate the efficacy of prevention and
      treatment for post-partum depression. METHOD: Subjects were screened with the
      Edinburgh Post-natal Depression Scale (EPDS) at the obstetric clinic. Mothers at
      risk (N = 258) (EPDS scores > or = 9) were randomly assigned to a
      prevention/treatment group or a control group. The prevention group received one
      cognitive-behavioural prevention session during hospitalization. At 4 to 6 weeks
      post-partum, subjects were screened again with the EPDS, after drop-out rates
      (refusals plus no return of the second EPDS) of 25.4% (33/130) in the
      intervention group and 10.9% (14/128) in the control group. Mothers with probable
      depression (EPDS scores > or = 11) were assessed using the Hamilton Depression
      Rating Scale (HDRS) and the Beck Depression Inventory (BDI). Mothers with major
      depression continued in the treatment group (N = 18) or in the control group (N =
      30). Treated subjects received a cognitive-behavioural programme of between five
      and eight weekly home-visits. RESULTS: Compared with the control group, women in
      the prevention group had significant reductions in the frequency of probable
      depression (30.2 % v. 48.2%). Recovery rates based on HDRS scores of < 7 and BDI
      scores of < 4 were also significantly greater in the treated group than in the
      control group. CONCLUSIONS: The study suggests that this programme for prevention
      and treatment of post-partum depression is reasonably well-accepted and
      efficacious.

PMID- 12214787
TI  - Progression to AIDS, a clinical AIDS condition and mortality: psychosocial and
      physiological predictors.
AB  - BACKGROUND: The primary aim of this study is to examine prospectively the
      association of stressful life events, social support, depressive symptoms, anger,
      serum cortisol and lymphocyte subsets with changes in multiple measures of human
      immunodeficiency virus (HIV) disease progression. METHODS: Ninety-six HIV
      infected gay men without symptoms or anti-retroviral medication use at baseline
      were studied every 6 months for up to 9 years. Disease progression was defined in
      three ways using the Centers for Disease Control (CDC) classifications (e.g.
      AIDS, clinical AIDS condition and mortality). Cox regression models with time
      dependent covariates were used, adjusting for control variables (e.g. race, age,
      baseline, CD4 T cells and viral load, number of anti-retroviral medications).
      RESULTS: Higher cumulative average stressful life events and lower cumulative
      average social support predicted faster progression to both the CDC AIDS
      classification and a clinical AIDS condition. Higher anger scores and CD8 T cells
      were associated with faster progression to AIDS, and depressive symptoms were
      associated with faster development of an AIDS clinical condition. Higher levels
      of serum cortisol predicted all three measures of disease progression.
      CONCLUSIONS: These results suggest that stressful life events, dysphoric mood and
      limited social support are associated with more rapid clinical progression in HIV
      infection, with serum cortisol also exerting an independent effect on disease
      progression.

PMID- 12214786
TI  - Personality disorders and depression.
AB  - BACKGROUND: Personality disorders (PDs) were assessed among depressed out
      patients by clinical interview before and after antidepressant treatment with
      fluoxetine to assess the degree of stability of PD diagnoses and determine
      whether changes in PD diagnoses across treatment are related to the degree of
      improvement in depressive symptoms. METHOD: Three hundred and eighty-four out
      patients (55% women; mean age = 39.9 +/- 10.5) with major depressive disorder
      (MDD) diagnosed with the SCID-P were enrolled into an 8 week trial of open
      treatment with fluoxetine 20 mg/day. The SCID-II was administered to diagnose PDs
      at baseline and endpoint. RESULTS: A significant proportion (64%) of our
      depressed out-patients met criteria for at least one co-morbid personality
      disorder. Following 8 weeks of fluoxetine treatment, there was a significant
      reduction in the proportion of patients meeting criteria for avoidant, dependent,
      passive-aggressive, paranoid and narcissistic PDs. From baseline to endpoint,
      there was also a significant reduction in the mean number of criteria met for
      paranoid, schizotypal, narcissistic, borderline, avoidant, dependent, obsessive
      compulsive, passive aggressive and self-defeating personality disorders. While
      changes in cluster diagnoses were not significantly related to improvement in
      depressive symptoms, there were significant relationships between degree of
      reduction in depressive symptoms (percentage change in HAM-D-17 scores) and
      degree of change in the number of criteria met for paranoid, narcissistic,
      borderline and dependent personality disorders. CONCLUSIONS: Personality disorder
      diagnoses were found to be common among untreated out-patients with major
      depressive disorder. A significant proportion of these patients no longer met
      criteria for personality disorders following antidepressant treatment, and
      changes in personality disorder traits were significantly related to degree of
      improvement in depressive symptoms in some but not all personality disorders.
      These findings suggest that the lack of stability of PD diagnoses among patients
      with current MDD may be attributable in part to a direct effect of antidepressant
      treatment on behaviours and attitudes that comprise PDs.

PMID- 12214788
TI  - Using an interleukin-6 challenge to evaluate neuropsychological performance in
      chronic fatigue syndrome.
AB  - BACKGROUND: Individuals with acute infections experience a range of symptoms
      including fatigue, malaise, muscle aches, and difficulties with concentration and
      memory that are usually self-limited. This cluster of symptoms is otherwise,
      similar to those that characterize chronic fatigue syndrome (CFS). The goal of
      the present study was to evaluate the cognitive and psychological functioning of
      CFS patients and normal controls (NCs) when they both were experiencing acute
      influenza-like symptoms. To induce influenza-like symptoms, we administered
      interleukin-6 (IL-6), a cytokine that temporarily activates the acute phase
      immunological and endocrine responses. METHODS: Nineteen patients who met the
      1994 International CFS Study Group Criteria and ten normal controls (NCs)
      completed routine clinical evaluations, neuropsychological tests of short-term
      memory, selective attention, and executive control, and self-ratings of somatic
      symptoms and psychological mood before, shortly following, and 1 day after IL-6
      administration. RESULTS: CFS patients consistently reported more somatic
      symptoms, even when both groups perceived that they were ill. Both groups somatic
      symptoms increased during the IL-6 challenge, but the CFS patients symptoms
      increased more rapidly than controls. In general, the CFS patients performed
      similarly to NCs on the cognitive measures before, during, and after the IL-6. In
      contrast to predictions, IL-6 provocation did not impair the cognitive
      performance of either CFS patients or NCs. CONCLUSIONS: The IL-6 provocation
      exacerbated the patients self-reported symptoms but did not reveal notable
      cognitive impairments between patients and controls during cytokine-induced acute
      influenza-like symptoms.

PMID- 12214789
TI  - Schizophrenia patients' perceptual biases in response to positively and
      negatively valenced emotion chimeras.
AB  - BACKGROUND: In a prior study, we observed that schizophrenia patients display
      atypical perceptual biases in response to emotional (happy/neutral) facial
      chimeras. METHODS: The present study was an attempt to replicate and extend those
      findings, using emotional stimuli with negative affective valence (angry/neutral
      chimeras) as well as positive valence, and including more than one type of non
      affective facial comparison task. We compared schizophrenia patients (N = 37) and
      controls (N = 48) on free-vision tasks that typically yield left spatial field
      biases indicative of right hemisphere activation. There were six chimera tasks,
      including two emotion (happy, angry) chimeras, two non-emotion (gender, age)
      chimeras and two non-face (dots, gradients) chimeras. RESULTS: We observed a
      Group x Task interaction, with schizophrenia patients displaying significantly
      less of the expected left spatial perceptual bias in response to the
      happy/neutral chimeras and the angry/neutral chimeras relative to the controls.
      In contrast, the patients and controls did not differ in terms of their response
      to the Gender, Age, Dots, or Gradients tasks. CONCLUSIONS: These findings are
      consistent with the assertion that, compared with healthy controls individuals
      with schizophrenia perceive emotion differently.

PMID- 12214790
TI  - Symptoms, cognition, treatment adherence and functional outcome in first-episode
      psychosis.
AB  - BACKGROUND: The differential strength of correlation between symptoms, cognition
      and other patient characteristics with community functioning in first-episode
      psychosis has not been fully investigated. METHOD: In a sample of 66 first
      episode psychosis patients demographic variables, ratings of pre-morbid
      adjustment, positive and negative symptoms, duration of untreated psychosis (DUP)
      and assessment of cognitive functions at baseline, and symptoms, cognitive
      functions and adherence to medication 1 year, were correlated with scores on
      social relations and activities of daily living (ADL) (outcome) at 1 year.
      Hierarchical regression analysis was used to confirm the independent contribution
      of baseline and concurrent variables to functional outcome at 1 year. RESULTS:
      Scores on functioning related to social relations and ADL were both significantly
      correlated with pre-morbid adjustment, all dimensions of residual positive and
      negative symptoms and adherence to medication at 1 year. Scores on social
      relations were also modestly correlated with DUP and several cognitive measures
      at baseline and 1 year (verbal IQ, attention, visual memory, word fluency and
      working memory). Hierarchical regression confirmed independent contribution of
      pre-morbid adjustment, total residual symptoms and adherence to medication at 1
      year for both dimensions of outcome, and psychomotor poverty and working memory
      for social relations. CONCLUSIONS: In addition to pre-morbid adjustment
      potentially malleable variables such as level of residual (but not acute)
      symptoms, adherence to medication and cognitive deficits are likely to influence
      outcome on aspects of community functioning in individuals treated for first
      episode of psychosis.

PMID- 12214791
TI  - Anxiety disorders and the onset of depression among adults in the community.
AB  - OBJECTIVE: To determine the association between anxiety disorders, panic attack
      and the risk of major depression among adults in the community. METHOD: Data were
      drawn from the Epidemiologic Catchment Area Program survey waves 1 (N = 20291)
      and 2 (N = 15849). Multivariate logistic regression analyses were used to
      determine the risk of incident major depression at 12-month follow-up (wave 2)
      associated with each anxiety disorder and panic attacks assessed at wave 1,
      adjusting for differences in sociodemographic characteristics, and then
      controlling simultaneously for all anxiety disorders, and other psychiatric co
      morbidity. RESULTS: Specific phobia (OR = 1.7 (1.6, 1.8)), agoraphobia (OR = 2.3
      (2.2, 2.5)), obsessive-compulsive disorder (OR = 5.4 (5.0, 5.8)) and panic attack
      (OR = 1.9 (1.8, 2.1)) each made an independent contribution to the risk of major
      depression, which persisted after adjusting simultaneously for sociodemographic
      differences and other psychiatric co-morbidity. CONCLUSIONS: Each anxiety
      disorder and panic attacks appear to confer an independent risk for the onset of
      major depression within 12-months among adults in the community. Understanding
      the key role played by anxiety in depression onset is needed for prevention
      strategies.

PMID- 12214792
TI  - Theory of mind deficit in people with schizophrenia during remission.
AB  - BACKGROUND: The authors' goal was to investigate the presence or absence of
      theory of mind impairments among people with schizophrenia during remission.
      Recent research results interpret theory of mind deficits as state rather than
      trait characteristics, connecting these impairments mainly to the acute episode
      of psychosis. METHODS: Twenty patients with schizophrenia in remission and 20
      matched control subjects were evaluated. Participants were presented with one
      first-order theory of mind task, one second-order theory of mind task, two
      metaphor and two irony tasks adapted from previous studies. RESULTS: The
      schizophrenic patients performed a statistically significant impairment in the
      irony task, as there were no significant differences in the cases of the other
      evaluated tasks. CONCLUSIONS: These preliminary results suggest that theory of
      mind impairments can be detected not only in the acute phase as found in previous
      research studies, but also in remission.

PMID- 12214793
TI  - Neurotic symptoms, stress, or deprivation: which is most closely associated with
      incidence of suicide? An ecological study of English Health Authorities.
AB  - BACKGROUND: Suicide rates, anxiety/depression scores and stress scores are
      routinely used as mental health indicators in populations, but their inter
      relationships have not been explored. Our aim was to explore the association of
      suicide rates with anxiety/depression and stress scores, while also referring to
      deprivation scores, which are known to be linked to suicide rates. METHODS: We
      undertook an ecological analysis of English Health Authorities, regressing
      suicide rates (1993-1994), on General Health Questionnaire and stress scores
      (1994), and also on Jarman deprivation scores (1991). RESULTS: Overall, Jarman
      deprivation score was a better predictor of suicide rate than the psychological
      distress measures. There were no statistically significant associations between
      suicide rates and GHQ scores, although there was a weak association between
      suicide rate and mean stress level in women. CONCLUSIONS: Suicide rates, though
      important in themselves, are not reliable indicators of the levels of neurotic
      symptoms or stress in populations. Suicide rates are more strongly associated
      with area-based measures of social disadvantage, though a possible stress-suicide
      relationship in women could be investigated further.

PMID- 12214794
TI  - The orexins/hypocretins: hypothalamic peptides linked to sleep and appetite.

PMID- 12214796
TI  - Age-period-cohort effects on inequalities in psychological distress, 1981-2000.
AB  - BACKGROUND: In the closing decades of the twentieth century, changes in
      population sociodemographics took place that might be thought to have an adverse
      influence on the nation's psychological distress. Here, we examine the stability
      of social and gender inequalities in psychological distress throughout the 1980s
      and 1990s. METHODS: The study uses data from the 1958 National Child Development
      Study and the 1970 British Cohort Study collected when the cohort members were
      aged between 23 and 42. Multilevel logistic regression models were used to
      examine the effects of social class, gender, age, period and cohort on
      psychological distress as measured by the Malaise Inventory. RESULTS: We identify
      clear social inequalities in psychological distress during 1981-2000 that reduced
      in magnitude over this period. Non-linear age effects were observed:
      psychological distress improves in early adulthood but declines again on
      approaching mid-life. The 1970 cohort had poorer psychological distress than the
      1958 cohort. Although women had higher rates of psychological distress than men,
      gender differences reduced in magnitude. Declining rates of women's psychological
      distress over time have not been matched in men. A reduction in social
      inequalities over time was also observed. Improvements in the psychological
      health of those in manual occupations were not equalled among those in non-manual
      occupations. CONCLUSIONS: Both social and gender inequalities have narrowed in
      the last two decades of the twentieth century.

PMID- 12214795
TI  - Short screening scales to monitor population prevalences and trends in non
      specific psychological distress.
AB  - BACKGROUND: A 10-question screening scale of psychological distress and a six
      question short-form scale embedded within the 10-question scale were developed
      for the redesigned US National Health Interview Survey (NHIS). METHODS: Initial
      pilot questions were administered in a US national mail survey (N = 1401). A
      reduced set of questions was subsequently administered in a US national telephone
      survey (N = 1574). The 10-question and six-question scales, which we refer to as
      the K10 and K6, were constructed from the reduced set of questions based on Item
      Response Theory models. The scales were subsequently validated in a two-stage
      clinical reappraisal survey (N = 1000 telephone screening interviews in the first
      stage followed by N = 153 face-to-face clinical interviews in the second stage
      that oversampled first-stage respondents who screened positive for emotional
      problems) in a local convenience sample. The second-stage sample was administered
      the screening scales along with the Structured Clinical Interview for DSM-IV
      (SCID). The K6 was subsequently included in the 1997 (N = 36116) and 1998 (N =
      32440) US National Health Interview Survey, while the K10 was included in the
      1997 (N = 10641) Australian National Survey of Mental Health and Well-Being.
      RESULTS: Both the K10 and K6 have good precision in the 90th-99th percentile
      range of the population distribution (standard errors of standardized scores in
      the range 0.20-0.25) as well as consistent psychometric properties across major
      sociodemographic subsamples. The scales strongly discriminate between community
      cases and non-cases of DSM-IV/SCID disorders, with areas under the Receiver
      Operating Characteristic (ROC) curve of 0.87-0.88 for disorders having Global
      Assessment of Functioning (GAF) scores of 0-70 and 0.95-0.96 for disorders having
      GAF scores of 0-50. CONCLUSIONS: The brevity, strong psychometric properties, and
      ability to discriminate DSM-IV cases from non-cases make the K10 and K6
      attractive for use in general-purpose health surveys. The scales are already
      being used in annual government health surveys in the US and Canada as well as in
      the WHO World Mental Health Surveys. Routine inclusion of either the K10 or K6 in
      clinical studies would create an important, and heretofore missing, crosswalk
      between community and clinical epidemiology.

PMID- 12214797
TI  - Does sexual violence contribute to elevated rates of anxiety and depression in
      females?
AB  - BACKGROUND: It is well documented that females have higher rates of internalizing
      disorders (anxiety, depression) than males. It is also well known that females
      have higher exposure to childhood sexual abuse and sexual assault. Recently, it
      has been proposed that the higher levels of internalizing disorders in females
      may be caused by their greater exposure to sexual violence. METHOD: Data were
      gathered as part of the Christchurch Health and Development Study. In this study
      a cohort of 1265 children born in Christchurch, New Zealand, in 1977 have been
      studied from birth to age 21 years. The measures collected included: major
      depression and anxiety, childhood sexual abuse and adolescent sexual assault.
      RESULTS: Findings confirmed the established conclusion that internalizing
      disorders are over twice as common in females than males (ORs 2.2-2.7). In
      addition, it was found that females were exposed to higher rates of sexual
      violence than males (ORs 5.1-8.4). Statistical control for gender related
      differences in exposure to sexual violence reduced the associations between
      gender and anxiety and depression. Nonetheless, even after such control, gender
      was significantly (P < 0.0001) related to both anxiety (OR = 1.8; 95% CI, 1.3
      2.4) and depression (OR = 1.9; 95% CI, 1.4-2.3). CONCLUSIONS: Greater female
      exposure to sexual violence may be a factor that contributes to greater female
      susceptibility to internalizing disorders. However, even after adjustment for
      gender differences in exposure to sexual violence it is clear that a substantial
      relationship between gender and internalizing disorder persists.

PMID- 12214798
TI  - Parental bonding and adult psychopathology: results from the US National
      Comorbidity Survey.
AB  - BACKGROUND: Research using the parental bonding instrument (PBI) has suggested
      that lack of parental care and/or overprotection may be important risk factors
      for adult mental disorders. Much of this research, however, has relied on
      clinical populations with one or two disorders, or has used highly select
      community samples. METHOD: The association between parenting experiences and the
      occurrence of 13 common mental disorders in adulthood was evaluated in the US
      National Comorbidity Survey (N = 5877). The effect of sociodemographic variables
      (age, education, income) was statistically controlled and the effects of six
      parenting variables (maternal and paternal care, overprotection and
      authoritarianism) were examined simultaneously. The effects in men and women were
      examined separately. RESULTS: Lack of care was the parenting variable most
      consistently associated with adult psychopathology. Parenting experiences with
      one's mother were more consistently associated with adult mental disorders. In
      general the impact of parenting was diagnostically non-specific. However, there
      appeared to be some unique effects for externalizing disorders (substance use
      disorders and antisocial personality disorder) in males; paternal overprotection
      and authoritarianism conferred a reduced risk of externalizing disorders in adult
      males. The overall impact of parenting as assessed by the PBI was modest,
      accounting for about 1 to 5 % of the variance in the occurrence of adult mental
      disorders. CONCLUSION: Parenting experiences, particularly lack of care, are
      potentially causally related in a non-specific manner to a wide variety of forms
      of adult psychopathology in both men and women. The overall magnitude of the
      effect is small but statistically significant in a nationally representative US
      sample.

PMID- 12214799
TI  - Impact of adding 5.5 mM glucose to SOF medium on the development, metabolism and
      quality of in vitro produced bovine embryos from the morula to the blastocyst
      stage.
AB  - Although toxic for early stages of embryo development, glucose is a physiological
      metabolic substrate at the morula and blastocyst stages. We evaluated the effect
      of adding 5.5 mM glucose from the morula stage on bovine blastocyst development
      and quality. In vitro matured and fertilised bovine oocytes were cultured in
      modified Synthetic Oviduct Fluid medium containing 5% fetal calf serum, but
      without added glucose, up to day 5 post-insemination (pi). Morulae were selected
      and further cultured in the presence or absence of 5.5 mM glucose. Blastocyst and
      hatched blastocyst rates were recorded. Oxygen, glucose and pyruvate uptakes as
      well as lactate release were evaluated. The quality of the resulting blastocysts
      was evaluated by the cell allocation to the inner cell mass (ICM) and
      trophectoderm (TE) and by the apoptotic index. Adding glucose increased the
      blastocyst rate at day 8 pi (80% vs 65%) but had no impact on hatching rate (25%
      vs 28%). A 22% decrease in oxygen uptake was observed in the presence of glucose,
      concomitant with an increase in lactate release, although no change was observed
      in pyruvate uptake. A slight decrease in blastocyst cell number was observed at
      day 7 in the presence of glucose while neither the ICM/TE cell ratio nor the
      apoptotic index were affected. In conclusion, adding 5.5 mM glucose from the
      morula stage has a limited impact on blastocyst rate and quality although
      important modifications were observed in embryo metabolism. It remains to be
      determined whether those modifications could influence embryo viability after
      transfer.

PMID- 12214800
TI  - Effect of Hoechst 33342 staining on developmental competence of prepubertal goat
      oocytes.
AB  - This study was undertaken to evaluate the effects of Hoechst staining on nuclear
      maturation and fertilisation when used at different stages of in vitro maturation
      (IVM) in prepubertal goat oocytes. Oocytes were matured in TCM1999 supplemented
      with 10% fetal bovine serum, 10 microg LH/ml, 10 microg FSH/ml and 1 microM
      17beta-estradiol for 27 h. Frozen-thawed sperm cells were prepared by
      centrifugation in a discontinuous Percoll gradient and resuspended in DMH medium
      with 20% steer serum. Oocytes were fertilised in DMH medium with 7.75 mM calcium
      lactate. During IVM oocytes were exposed to 0.5 microg/ml of Hoechst 33342
      staining and to ultraviolet light for a mean time of 3 s at 0 h, 8 h, 15 h, 20 h
      and 27 h. The percentage of metaphase II oocytes decreased significantly when
      oocytes were stained with Hoechst dye at 0 h, 8 h and 15 h of IVM. There was a
      decrease in total fertilisation rate and normal fertilisation rate of Hoechest
      stained oocytes, independently of the time of Hoechst staining. Hoechst staining
      produces a significant reduction in oocyte viability when it is used in the early
      stages of in vitro maturation.

PMID- 12214801
TI  - Generation of transgenic mice by transfection of pronuclear embryos using lipid
      DNA complexes.
AB  - We had previously developed a methodology to introduce foreign DNA into mouse
      eggs and embryos using cationic lipids as vectors. In this report we use this
      technique to produce transgenic animals. Mouse embryos at the pronuclear stage
      were transfected using a mixture of a plasmid DNA, encoding for a nuclear form of
      beta-galactosidase, and a commercial lipid transfection reagent. Embryos were
      washed and incubated overnight. Those that cleaved and develop to the 2-cell
      stage of normal appearance were transferred to the Fallopian tubes of
      pseudopregnant foster mothers. We analysed a total of 158 offspring and found
      two, a female and a male, to be transgenic (1.27% of the total). Integration of
      the foreign DNA in the female was showed by Southern blot. Both animals expressed
      the lacz in several organs, but none of them either displayed expression in the
      germ cells or transmitted the transgene to their offspring. Taken together our
      results show that lipid transfection can generate transgenic mice, but the
      efficiency needs to be improved for this method to be widely applied.

PMID- 12214802
TI  - Effect of delayed enucleation on the developmental potential of nuclear
      transferred oocytes receiving adult and fetal fibroblast cells.
AB  - To enhance the probability of reprogramming somatic cell nuclei, fibroblast cells
      from an adult male rabbit and a 12-day-old fetus were fused with oocytes at the
      second metaphase. The chromosomes of recipient oocytes were then removed by
      treatment with demecolcine for 1 or 2 h after fusion. Demecolcine treatment of
      fused oocytes induced membrane protrusions that contained all the maternal
      chromosomes, thus making it possible to remove the chromosomes. The potential of
      nuclear-transferred oocytes to develop into blastocysts was high (48% and 59%)
      and the average cell number of the blastocysts was large (149 and 159) 96 h after
      in vitro culture. The proportions of nuclear-transferred oocytes enucleated 1 h
      after fusion and implanted after transfer to pseudopregnant recipients were
      relatively high (2.8% and 4.9%) compared with our previous reports (1.7%: Yin et
      al., 2000; 0.6% and 1.0%: Yin et al., 2002a) where donor cells were fused with
      previously enucleated oocytes. Of 34 adult somatic cell implantation sites, 6 had
      fetuses on day 12 or 14 of pregnancy, but none of the fetuses had a heart beat or
      developed to term. None of the nuclear-transferred oocytes whose chromosomes were
      removed 2 h after demecolcine treatment implanted after transfer to recipients.
      The possible reasons why the high-quality nuclear-transferred oocytes did not
      develop to term are discussed.

PMID- 12214803
TI  - Microtubules and parental genome organisation during abnormal fertilisation in
      humans.
AB  - We analysed the distribution of beta-tubulins, acetylated alpha-tubulins and
      chromatin configuration in 113 human zygotes showing abnormal fertilisation, 16
      18 h after conventional in vitro fertilisation (IVF) or intracytoplasmic sperm
      injection (ICSI). After a first characterisation using phase contrast microscopy,
      immunofluorescence staining was performed in 67 IVF and 46 ICSI zygotes that
      developed one, three or more pronuclei and/or subnuclei, with or without
      extrusion of the second polar body. Independently of the number of pronuclei
      found, beta-tubulins were uniformly distributed throughout the cytoplasm of the
      abnormal zygotes. We did not observe any kind of microtubule alteration with
      respect of the ploidy level and/or its origin. The most frequent abnormal
      fertilisation pattern found after IVF was the presence of three or four pronuclei
      (74.6%). On the other hand, the presence of one pronucleus (63.0%) was the main
      pattern found after ICSI. No differences between the two groups were seen in
      terms of development of subnuclei. Anamolies detected after IVF and ICSI showed
      different aetiologies such as parthenogenetic activation, gynogenetic or
      androgenetic development, as well as digynic or diandric fertilisation.

PMID- 12214804
TI  - DNA replication and RNA synthesis in thymocyte nuclei microinjected into the
      cytoplasm of artificially activated mouse eggs.
AB  - Thymocyte nuclei were microinjected into the cytoplasm of parthenogenetic mouse
      eggs within 60 min or 3 h after egg activation and DNA replication and RNA
      synthesis were analysed in remodelled thymocyte nuclei and female pronuclei. We
      show that thymocyte nuclei which transform into pronucleus-like nuclei
      (thymocytes injected not later than 60 min after activation) enter S-phase 1 h
      earlier than the female pronuclei. At the beginning of the first cell cycle they
      remain transcriptionally silent, but in G2 undertake transcription earlier than
      the female pronuclei. Partly remodelled thymocyte nuclei (injected 3 h after
      activation) start to replicate DNA at the same time as the female pronuclei. They
      reinitiate RNA synthesis within 2 h after transfer and continue to transcribe
      irrespective of the transcriptional activity of the female pronucleus. We show
      that the observed transcription is only nuclear, i.e. RNA polymerase II
      dependent.

PMID- 12214805
TI  - Quantification of basigin mRNA in mouse oocytes and preimplantation embryos by
      competitive RT-PCR.
AB  - Basigin is a member of the immunoglobulin superfamily and a key molecule related
      to mouse blastocyst implantation. Whether preimplantation mouse embryos express
      basigin mRNA is still unknown. The aim of this study was to use a quantitative
      competitive polymerase chain reaction to assess quantitatively the levels of
      basigin mRNA in mouse oocyte and preimplantation embryos. Basigin mRNA was
      detected in the oocyte and all the stages of preimplantation embryos. The levels
      of basigin mRNA were 0.0606 +/- 0.0282 in the oocyte, 0.0102 +/- 0.0036 in the
      zygote, 0.0007 +/- 0.0003 in the 2-cell embryo, 0.0031 +/- 0.0017 in the 4-cell
      embryo, 0.0084 +/- 0.0024 in the 8-cell embryo, 0.0537 +/- 0.0121 in the morula
      and 0.0392 +/- 0.0161 attomoles in the blastocyst, respectively. The levels of
      basigin mRNA in the oocyte, morula and blastocyst were significantly higher than
      those in the zygote and embryos at the 2-cell, 4-cell and 8-cell stages. The high
      level of basigin expression in the blastocyst may play a role during embryo
      implantation.

PMID- 12214806
TI  - Determination and synchronisation of G1-phase of the cell cycle in 2- and 4-cell
      mouse embryos.
AB  - Incorporation of [3H]thymidine at different concentrations into mouse embryos at
      early developmental stages was determined by autoradiography. Methods to
      synchronise the G1-phase of mouse 2- and 4-cell embryos were also investigated.
      The results showed that the ability of embryos to incorporate [3H]thymidine
      increased with development. Embryos at the 4-cell stage were not labelled when
      the concentration of [3H]thymidine was lower than 5 microCi/ml, whereas the
      nuclei of embryos at morula and blastocyst stages began to show silver grains at
      a concentration of 0.1 microCi/ml of [3H]thymidine. After 2- and 4-cell mouse
      embryos were synchronised at the onset of G1-phase by treatment with low
      temperature or nocodazole, and DNA synthesis was detected by autoradiography, the
      duration of G1-phase was estimated. The result showed that 43% of the 2-cell
      embryos had a G1-phase of < or = 1 h, 22% had a G1-phase of < or = 2 h, 22% had a
      G1-phase of < or = 3 h and 13% had a G1-phase of < or = 4 h. The G1-phase in 85%
      of the 4-cell embryos was < or = 3 h, that in 8% of embryos was < or = 4 h and
      that in 7% of embryos was < or = 5 h. The toxicity of nocodazole on mouse embryo
      development was assessed based on both blastocyst formation and the number of
      blastomeres, and the results indicated that the effect of nocodazole on embryo
      development and cell cycle block was dose-dependent. The minimum concentration of
      nocodazole for metaphase block of mouse late 2-cell embryos was 0.05 microM, and
      the appropriate concentrations which did not impair development were 0.05-0.5
      microM.

PMID- 12214807
TI  - Extracellular and intracellular factors affecting nuclear and cytoplasmic
      maturation of porcine oocytes collected from different sizes of follicles.
AB  - Nuclear and cytoplasmic maturation of porcine oocytes collected from different
      sizes of follicles were examined. Oocyte-cumulus complexes were collected from
      small (1-2 mm in diameter), medium (3-6 in diameter) and large (7-8 mm in
      diameter) follicles and cultured in a modified tissue culture medium 199 for 44
      h. Nuclear maturation was evaluated after orcein staining, and cytoplasmic
      maturation was evaluated by intracellular glutathione (GSH) assay. Oocyte
      diameter, cumulus morphology, steroid hormones and glutathione in the follicular
      fluid (FF), were also examined. Significantly higher proportions of oocytes
      collected from large and medium follicles reached metaphase II than did oocytes
      from small follicles. Oocytes from small follicles also had a smaller size. GSH
      content was significantly higher (p < 0.05) in oocytes from large (14.24 +/- 2.1
      pmol/oocyte) and medium (13.69 +/- 1.5 pmol/oocyte) follicles than in oocytes
      from small (9.44 +/- 1.28 pmol/oocyte) follicles just after collection. After
      maturation, oocytes from medium follicles had a higher GSH concentration than
      oocytes from small follicles. It was found that between 49.7 +/- 5.18 nM and
      52.25 +/- 0.78 nM GSH was present in FF but there was no statistical difference
      between follicle sizes. A significantly higher (p < 0.001) estradiol level was
      present in FF from large follicles (299.2 +/- 68.6 ng/ml) than from medium (40.0
      +/- 6.4 ng/ml) and small (41.2 +/- 3.7 ng/ml) follicles. Progesterone
      concentrations in FF from large (281.6 +/- 45.9 ng/ml) and medium (267.5 +/- 38.6
      ng/ml) follicles were significantly higher than that (174.7 +/- 22.0 ng/ml) from
      small follicles. These results indicate that the oocyte's ability to accumulate
      intracellular GSH during maturation, and extracellular steroid hormones and
      cumulus cells, affect the competence of porcine oocytes to undergo nuclear and
      cytoplasmic maturation.

PMID- 12214808
TI  - Acquisition of meiotic competence in growing pig oocytes correlates with their
      ability to activate Cdc2 kinase and MAP kinase.
AB  - Meiotic maturation of mammalian oocytes is under the control of cell cycle
      molecules Cdc2 kinase and MAP kinase (mitogen-activated protein kinase). In the
      present study, we investigated the relationship between the ability to activate
      Cdc2 kinase and MAP kinase and the acquisition of meiotic competence during pig
      oocyte growth. Growing and fully grown pig oocytes were collected from four
      groups of antral follicles of various diameters (A, 0.5-0.7 mm; B, 1.0-1.5 mm; C,
      2.0-2.5 mm; D, 4.0-6.0 mm) and cultured in vitro. Fully grown oocytes from class
      D follicles, which have full competence to mature to metaphase II, had the
      ability to activate both Cdc2 kinase and MAP kinase. In contrast, growing oocytes
      from class A follicles, which have limited competence to resume meiosis, had no
      such ability. Cyclin B1 molecules did accumulate, however, with phosphorylated 35
      and 36 kDa bands of p34cdc2 appearing in the cultured oocytes. Of the growing
      oocytes from class B follicles, 60% resumed meiosis but arrested at metaphase I.
      Some of the oocytes in this class were capable of activating Cdc2 kinase,
      although they did not appear to have established a MAP kinase-activating pathway
      or the ability to activate MEK. These results suggest that limited meiotic
      competence in growing oocytes from class A follicles is due to their inability to
      activate Cdc2 kinase and their incomplete MEK-MAP-kinase pathway, although the
      oocytes are capable of accumulating cyclin B1 molecules. During the final growth
      phase, pig oocytes acquire the ability to activate Cdc2 kinase and then establish
      the MEK-MAP-kinase pathway for full meiotic competence.

PMID- 12214809
TI  - Involvement of catecholamines in the regulation of oocyte maturation in frogs.
AB  - The present study investigates the role of catecholamines in the regulation of
      Bufo arenarum oocyte maturation. The metabolic changes in the oxidation of
      carbohydrates and the meiotic resumption evinced by the germinal vesicle
      breakdown were used as indicators of cytoplasmic and nuclear maturation,
      respectively. The results obtained suggest that noradrenaline (norepinephrine)
      could be one of the factors responsible for the metabolic behaviour that
      characterises cytoplasmically immature oocytes. The use of adrenaline
      (epinephrine), on the other hand, induced a metabolic change which made oocytes
      cytoplasmically mature. The effect of both catecholamines, which was dose
      dependent, was observed in ovarian oocytes (surrounded by follicle cells) as well
      as in coelomic oocytes (free from follicle cells), suggesting the presence of
      adrenergic receptors in the gamete. The results obtained using adrenergic
      agonists and antagonists suggest that the effect of adrenaline would be due to an
      interaction with beta2-receptors. Although catecholamines have an influence on
      the determination of the stage of cytoplasmic maturation of the oocytes, they do
      not affect nuclear maturation by themselves. Nevertheless, pretreatment of
      follicles with adrenaline caused a significant inhibition in progesterone-induced
      nuclear maturation even though this effect was markedly weaker when using
      noradrenaline.

PMID- 12214810
TI  - Naturalistic manner of benzodiazepine use and cognitive behavioral therapy
      outcome in panic disorder with agoraphobia.
AB  - Benzodiazepines (BZs) are commonly used in conjunction with cognitive behavioral
      therapy (CBT) in the treatment of panic disorder with agoraphobia (PDA). However,
      empirical evidence provides little support for the utility of this combined
      treatment approach over CBT alone. Westra and Stewart [Clin. Psychol. Rev. 18
      (1998) 307] have proposed that pm or as-needed use of BZs may inhibit positive
      CBT outcome to a greater extent than regularly scheduled BZ use. Using a
      naturalistic design, the present study investigated the impact of manner of BZ
      use on treatment outcome from CBT in 43 patients with PDA. Among various BZ
      parameters (chronicity, frequency, dose, and frequency of prn use), pm use of BZs
      for coping with anxiety symptoms was a significant negative predictor of degree
      of change in both anxiety sensitivity and anxious arousal from pre- to post-CBT.
      Although no significant between-group differences were evident in pre-treatment
      symptomatology, unmedicated subjects demonstrated the most positive overall CBT
      outcome, while pm BZ users evidenced the fewest gains. Regular BZ users were
      generally not significantly differentiated from unmedicated subjects in CBT
      outcome and both tended to obtain post-treatment scores in the nonclinical range.
      Implications of these findings for clinical management of BZ use throughout CBT
      for PDA are discussed.

PMID- 12214811
TI  - Global cerebral blood flow after CO2 inhalation in normal subjects and patients
      with panic disorder determined with [15O]water and PET.
AB  - OBJECTIVE: To determine the effect of CO2 inhalation on global cerebral blood
      flow (gCBF) and pCO2-adjusted gCBF in normal subjects and panic disorder
      patients. METHOD: Global cerebral blood flow was determined using quantitative
      [15O] water imaging in normal subjects (n = 12) and panic disorder patients (n =
      14) after inhalations of medical grade air and of 35%/65% CO2/O2 mixture, a known
      inducer of panic. The gCBF was calculated as an area-weighted mean value. The
      pCO2 -adjusted gCBF values were calculated based on the formula of Reiman et al.
      [Am. J. Psychiatr. 143 (1986) 469]. Data were analyzed using repeated-measures
      ANOVA and regression analyses. RESULTS: The pCO2 values did not differ
      statistically between normals and panic patients. Panic patients exhibited a
      decrease in gCBF and stable pCO2-adjusted gCBF values in comparisons of AIR and
      CO2 inhalations, whereas normals exhibited stable gCBF and increasing pCO2
      adjusted gCBF values. CONCLUSIONS: Patients with panic disorder, especially when
      symptomatic, exhibited an abnormal pattern in gCBF response to provocation.

PMID- 12214812
TI  - The incidence and influence of early traumatic life events in patients with panic
      disorder: a comparison with other psychiatric outpatients.
AB  - Early traumatic life events, including childhood physical and sexual abuse, has
      been associated with increased risk for panic disorder in adulthood. We examined
      the incidence and influence of early traumatic life events in outpatients with
      panic disorder (n = 101), compared to outpatients with other anxiety disorders (n
      = 58), major depression (n = 19), or chronic schizophrenia (n = 22). Data were
      obtained by means of Structured Clinical Interviews and self-report
      questionnaires. The incidence of childhood physical abuse ranged from 16 to 40%
      and for childhood sexual abuse from 13 to 43% with no significant differences
      among the four diagnostic groups. Across all outpatient groups a history of
      childhood physical or sexual abuse was positively correlated to clinical
      severity. Patients with panic disorder who reported childhood physical abuse were
      more likely to be diagnosed with comorbid depression, to have more comorbid Axis
      I disorders, to score higher on symptom checklists as well as reporting a greater
      history of suicide attempts in the past year (5% vs. 0%); or lifetime (36% vs.
      15%). Similar findings were noted, but not as robustly, for patients with panic
      disorder who reported childhood sexual abuse. There is a high rate of adverse
      early childhood events across diagnostic groups in psychiatric outpatients and
      these events are likely to influence the severity of the disorder but are
      unlikely to be a unique risk factor for any one type of disorder.

PMID- 12214813
TI  - Efficacy of Eye Movement Desensitization in the treatment of cognitive intrusions
      related to a past stressful event.
AB  - Much of the Eye Movement Desensitization and Reprocessing (EMDR) efficacy
      research has been widely criticized, limiting scientific understanding of its
      therapeutic components. The present investigation of Eye Movement Desensitization
      (EMD) effectiveness included undergraduate students reporting current intrusive
      cognitions conceming a traumatic event. Forty-five participants received a single
      treatment session of either: (a) EMD, as described by Shapiro [J. Behav. Ther.
      Exp. Psychiatry 20 (1989b) 211], (b) an identical procedure which employed eye
      fixation on a stationary target, or (c) non-directive counseling. Standardized
      self-report, subjective rating, Daily Diary, and intrusive thought sampling
      measures were collected before and after treatment. Results indicated that
      participants in the eye fixation group reported marginally (p < .052) fewer
      cognitive intrusions than the non-directive group 1 week following treatment. No
      significant differences between the EMD and non-directive conditions or between
      the EMD and eye fixation conditions on this measure were found. During the
      treatment session, both desensitization groups were superior to the non-directive
      group in reducing reported vividness of the mental image of the original event.
      However, the non-directive group improved to the level of the two other groups by
      the following week. Rapid saccadic eye movements were therefore unrelated to
      immediate treatment effects for this sub-clinical sample, and non-directive
      treatment largely yielded eventual outcomes equivalent to the two desensitization
      conditions.

PMID- 12214814
TI  - Selective processing of emotional information in body dysmorphic disorder.
AB  - Body dysmorphic disorder (BDD) is a syndrome characterized by distress about
      imagined defects in one's appearance. Though categorized as a somatoform
      disorder, BDD is marked by many characteristics associated with social phobia
      (e.g., fear of negative evaluation) and obsessive-compulsive disorder (e.g.,
      intrusive thoughts about one's ugliness, checking). In the present experiment, we
      tested whether BDD patients exhibit selective processing of threat in the
      emotional Stroop paradigm as do anxiety-disordered patients. Relative to healthy
      control participants, BDD patients exhibited greater Stroop interference for
      positive and negative words, regardless of disorder-relevance, than for neutral
      words. Further analyses suggested that interference tended to be greatest for
      positive words related to BDD. These data suggest that BDD patients are
      vulnerable to distraction by emotional cues in general, and by words related to
      their current concerns in particular. Results suggest that BDD may indeed be
      related to anxiety disorders such as social phobia.

PMID- 12214815
TI  - Symptom presentations of older adult crime victims: description of a clinical
      sample.
AB  - Psychological sequelae of interpersonal violence in older adults remain
      understudied. Existing investigations focused on the clinical presentation of
      older adults who were traumatized as young adults (e.g., combat veterans).
      Consequently, little is known about the clinical correlates of trauma in recently
      victimized older adults. This descriptive study attempt to fill this void by
      documenting the symptom status and demographic features of 36 treatment-seeking
      older adult crime victims. Results indicated that older adult crime victims who
      seek services are a multiply traumatized group. They experienced significant
      financial, educational, medical, and social stressors that may complicate their
      clinical picture and treatment progress. Additionally, older adult crime victims
      experienced moderate-to-severe levels of psychopathology as evidenced by symptoms
      endorsed on an array of structured clinical interviews and paper-and-pencil
      measures designed to measure symptoms of Posttraumatic Stress Disorder (PTSD),
      depression, and panic.

PMID- 12214816
TI  - Stability of worry content in GAD patients: a descriptive study.
AB  - The stability of worry content was investigated in a sample of 27 individuals
      diagnosed with Generalized Anxiety Disorder. During an initial evaluation,
      participants were asked to describe the content of their current worries, and the
      examining psychiatrist rated the frequency and intensity of these topics. During
      the following year, the investigators interviewed the participants on a monthly
      basis assessing the intensity and frequency of original worries, intensity and
      frequency of new worries, overall worry level, and general anxiety level.
      Analysis of this longitudinal data indicated level of overall worry and anxiety
      remained fairly stable over a 12-month period. Although the intensity and
      frequency of original worries decreased over time, few original worry topics
      completely remitted. In fact, at the end of the 12-month monitoring period, worry
      content identified at baseline continued to account for over 65% of the overall
      worry variance. Most participants did identify new worry topics during the course
      of the 12-month period, and the frequency and intensity of the new worries were
      comparable to the decrease in frequency and intensity of the original worries.

PMID- 12214817
TI  - The etiology of childhood dental fear: the role of dental and conditioning
      experiences.
AB  - This study was aimed to examine the relative importance of invasive treatment
      experiences in the acquisition of dental fear in children. For this purpose, the
      complete dental history of 401 children (5-10 years) was studied. The level of
      dental fear in these children was assessed using the Dental Subscale of the
      Children's Fear Survey Schedule (CFSS-DS). Differences in treatment variables
      between fearful and low fearful children were analyzed, and regression analysis
      was performed to determine significant predictors of dental fear. A significant
      but weak relation with the number of extractions was found, while no relation
      with the number of fillings was found. The results have indicated that within the
      (direct) conditioning pathway, objective dental experiences seem to play a minor
      role in children's fear acquisition, and it was suggested that subjective dental
      experiences may play a more decisive role. In addition, clinical support for the
      latent inhibition theory was provided.

PMID- 12214818
TI  - Assessing the severity of panic disorder and agoraphobia: validity, reliability
      and objectivity of the Turkish translation of the Panic and Agoraphobia Scale
      (P&A).
AB  - The aim of the present study was to determine the psychometric properties of the
      Turkish translation of both the observer-rated (P&Ao) and self-rated (P&As)
      versions of the Panic and Agoraphobia Scale (P&A). Discriminant and convergent
      validity of P&A were assessed in patients with panic disorder with or without
      agoraphobia (n = 119), by comparing the P&A with the Clinical Global Impression
      Scale (CGI), Hamilton Anxiety Scale (HAMA), Phobia and Anxiety sub-scales of
      Symptom Check List, Spielberger State and Trait Anxiety Inventory and the Beck
      Depression Inventory (BDI). Inter-rater and test-retest reliability were
      determined. Correlation coefficients between the CGI and the P&Ao and the P&As
      were .85 and .74, respectively, and .85 between the two versions of the P&A.
      Cronbach's alpha for the P&Ao, and the P&As was .88 and .86, respectively. The
      Turkish version of the P&A has yielded good psychometric properties and was found
      to be a reliable instrument for assessing severity in panic disorder.

PMID- 12214819
TI  - Cognitive-behavioral treatment of food neophobia in adults.
AB  - Food neophobia is an eating disturbance defined as the fear of trying new foods.
      In its extreme, the disorder can lead to malnutrition, limited social
      functioning, and psycholo gical difficulties. Successful treatment of food
      neophobia in children has been reported, but if those children are not provided
      with treatment, it stands to reason that the disorder may follow them into
      adulthood. To date, adult cases have not been described in the literature and the
      prevalence in adults is unknown. Our paper will review the methods used to treat
      children with the disorder, then delineate how the procedures were modified for
      an adult population, giving two case examples.

PMID- 12214820
TI  - The trail making test, part B: cognitive flexibility or ability to maintain set?
AB  - The Trail Making Test (TMT) is a well-established test sensitive to impairment in
      multiple cognitive domains. There has been ambiguity about which cognitive
      demands are placed on the patient by TMT Part B over and above those required to
      perform TMT Part A. In particular, cognitive flexibility and ability to maintain
      a complex response set have been 2 competing hypotheses. This study preliminarily
      examined which of these 2 abilities primarily contributes to Part B performance.
      A total of 121 clinically referred Veterans Affairs patients were administered
      the TMT, as well as other tests of executive and other cognitive functions.
      Regression analyses were used to examine which tests predicted Part B performance
      above and beyond Part A performance. The results provide preliminary support for
      TMT Part B performance being more sensitive to cognitiveflexibility
      (operationalized as Wisconsin Card Sorting Test [WCST], percent perseverative
      errors) than ability to maintain set (operationalized as WCST, failure to
      maintain set).

PMID- 12214821
TI  - Normative data for healthy elderly persons with the neurobehavioral cognitive
      status exam (Cognistat).
AB  - This study provides normative data about the cognitive functioning of 134
      nonpsychiatric, non-neurological healthy elderly persons ranging from 60 to 85
      years of age with the Neurobehavioral Cognitive Status Examination (Cognistat).
      Most areas of cognitive functioning remain grossly intact for all age levels.
      Construction and memory showed evidence of decline with age. These findings were
      compared with previous normative research with the Cognistat.

PMID- 12214822
TI  - Construct validity of the Babcock Story Recall Test.
AB  - The construct validity of the Babcock Story Recall Test (BSRT), a verbal memory
      measure, was examined by correlating its scores with scores on other
      neuropsychological tests in 71 substance abuse outpatients. Scores on the BSRT
      were strongly correlated with the Wechsler Memory Scale-Revised Logical Memory
      scores, although they were also correlated with some nonmemory indexes. The
      results provide some support for the construct validity of the BSRT as a measure
      of memory for structured verbal information.

PMID- 12214823
TI  - Is the use of the wooden and computerized versions of the Tower of Hanoi puzzle
      equivalent?
AB  - The purpose of this study was to examine whether a computerized administration of
      the Tower of Hanoi (TH) puzzle is equivalent to the classic wooden version of
      this test. Two groups of healthy volunteers were administered the 2 versions of
      the TH in a randomized counterbalanced design. The results showed no differences
      between the 2 versions of the TH on any dependent variable, indicating that their
      use is equivalent. Men performed better than women in this test, although this
      finding was independent of the TH version administered. It remains to be tested
      whether age and computer experience affect performance differentially on the
      computerized and the wooden versions of the TH puzzle and whether these results
      are replicated in brain-damaged patients.

PMID- 12214824
TI  - Differences in young children's IQs on the Wechsler preschool and primary scale
      of intelligence-revised as a function of stratification variables.
AB  - The normative sample (N = 1,700) of the Wechsler Preschool and Primary Scale of
      Intelligence-Revised (WPPSI-R), stratified on age, gender, ethnicity, geographic
      region, education, and occupation of children's parents, served as the database
      with which to examine the associations of demographic characteristics with Verbal
      Intelligence Quotients (VIQs), Performance Intelligence Quotients (PIQs), and
      Full Scale Intelligence Quotients (FSIQs) among young children. A 3-way
      multivariate analysis of variance (MANOVA) andfollow-up analyses of variance
      (ANOVAs) found significant effects of parent education and ethnicity, but not
      child's gender, on IQ. A separate 2-way MANOVA andfollow-up ANOVAsfound
      significant interaction effects between region and ethnicity on IQ. Parent
      education showed the largest association with all 3 IQs, whereas gender and age
      showed the least. The meaning of the hierarchy of the stratification variable
      associations with IQ is discussed.

PMID- 12214825
TI  - Does the child behavior checklist reveal psychopathological profiles of children
      with focal unilateral cortical lesions?
AB  - Psychopathological profiles were investigated in children with focal unilateral
      radiologically documented cortical lesions (15 right lesions and 22 left
      lesions). The 8 clinical subscales of the Child Behavior Checklist Parent Form
      (CBCL-P) and the Internalizing and Externalizing subscales were the dependent
      measures. The Internalizing and Externalizing scores did not dissociate as a
      function of lesion side. There were more Internalizing than Externalizing
      symptoms. Only the Attention Problems subscale yielded a significant difference
      as a function of lesion side; children with left lesions unexpectedly presented
      more problems. No significant differences were observed as a function offrontal
      versus nonfrontal lesion site, gender, or neurological variables on the Child
      Behavior Checklist (CBCL) subscales. Although sensitive to the presence of a
      focal lesion, the CBCL-P scarcely or misleadingly reflects any of the
      characteristics offocal unilateral cortical lesions in children. As suggested by
      the literature, most of the CBCL elevations in children with brain lesions could
      derive from the parent's and child's emotional response to any threatening
      medical condition.

PMID- 12214826
TI  - Attentional processes in abstinent methylenedioxymethamphetamine (ecstasy) users.
AB  - In recent years, methylenedioxymethamphetamine (MDMA or ecstasy) has gained great
      popularity among young adults. Although human research in abstinent users has
      focused primarily on memory function, little attention has been given to other
      neuropsychological functions that may have some bearing on memory performance,
      such as attention. Hence, the purpose of this study was to examine the effects of
      MDMA on attentional processes. Accordingly, 24 MDMA users and 30 matched normal
      controls were tested on the Wechsler Abbreviated Scale of Intelligence (WASI) and
      the Test of Everyday Attention (TEA). We found MDMA users to show generally no
      significant difference on attention tasks compared with controls with the
      exception of a single TEA subtest. More interestingly, we found some preliminary
      evidence to indicate that dosage, in terms of the number of tablets used, may be
      related to impairment on specific component attentional tasks. This finding
      brings to light the important relationship between poor attentional processes and
      drug-taking behaviors and their reciprocal relationship.

PMID- 12214827
TI  - A review of the use of single-photon emission computerized tomography as a
      diagnostic tool in mild traumatic brain injury.
AB  - The aim of this literature review was to follow up on recommendations set forth
      in 1996 reviews by the Society for Nuclear Medicine Brain Imaging Council
      (SNMBIC) and the Therapeutics and Technology Assessment Subcommittee of the
      American Academy of Neurology (TTASAAN) regarding the use of single-photon
      emission computerized tomography (SPECT) with mild traumatic brain injury (MTBI).
      An extensive review of databases was conducted to determine studies analyzing
      MTBI that used SPECT as a diagnostic tool between the years of 1966 and 2000.
      Although only 9 studies met the established criteria, the review suggests that
      SPECT may be a useful tool in the detection of MTBI and in treatment planning.
      However, because of the lack of consensus regarding SPECT's sensitivity, it is
      recommended that future researchers consider the possibility of multiple subtypes
      of MTBI, hemodynamically different types of contusions, and the need for
      complementary diagnostic tools.

PMID- 12214828
TI  - Radiation therapy for gynecologic cancer.

PMID- 12214829
TI  - Multiparametric flow cytometric analysis in a breast cancer cell line (MCF-7).
AB  - OBJECTIVE: To investigate whether multiparameter flow cytometric analysis of
      solid tumor specimens, including gynecologic tumors, which were stained triply
      with phycoerythrin (PE), fluorescein isothiocyanate (FITC) and propidium iodide
      (PI), can be performed simultaneously without interference from normal diploid
      cell populations and spectral overlap on a standard flow cytometer. METHODS: MCF
      7 breast cancer cell lines and heterogeneous cell populations mixed with MCF-7
      cells and human peripheral blood lymphocytes (PBL) were fixed with 1%
      paraformaldehyde and permeabilized with 100% methanol. Cytokeratin and several
      proliferation-associated cellular antigens (proliferating cell nuclear antigen
      (PCNA), p53, c-erbB/2 and c-myc) were labeled with PE and FITC, which was
      followed by DNA staining using PI. These labeled cells were measured on a
      standard FACScan flow cytometer equipped with a 488 nm single laser. RESULTS: The
      coefficient of variation (CV) of the G0G1 peak of MCF-7 cells was 4.3 and the
      cell cycle phase fractions of G0G1, S and G2M were 44.9, 45.9 and 9.2%,
      respectively. Fluorescein isothiocyanate, PE and PI fluorescences were detected
      without interference. The MCF-7 cells expressed cytokeratin, PCNA, p53, c-erbB/2
      and c-myc antigen. In the heterogeneous population of MCF-7 cells mixed with PBL,
      two cellular populations were clearly separated into diploid PBL and aneuploid
      MCF-7 cells without interference. The CV of G0G1 peak of PBL was 2.3 and the
      G0G1, S and G2M phase fractions were 85.5, 2.7 and 11.8%, respectively. The DNA
      index of MCF-7 cells was 1.7, which indicated that the MCF-7 cell line was
      composed of tumor cells with aneuploid DNA. The CV of the G0G1 peak of the MCF-7
      cells was 4.2, and the cell cycle phase fractions were 47.5% for G0G1, 42.3% for
      S, and 10.2% for G2M. The MCF-7 cells expressed cytokeratin, but the PBL did not.
      CONCLUSIONS: Multiparameter flow cytometer analysis was useful to determine DNA
      ploidy status, phase fraction of the cell cycle and expression of cellular
      antigens and selective cytokeratin expression allowed epithelial originated tumor
      cells to be differentiated from normal stromal cells. This analysis could be
      performed without interference of spectral overlaps of fluorochromes using
      software-based algorithmic compensation of spectral overlaps. Thus, this method
      offers new possibilities for multiparameter flow cytometric analysis and its use
      should be extended to future studies of the diagnosis, treatment and prediction
      of prognosis of the neoplasm.

PMID- 12214830
TI  - A prospective randomized study comparing retroperitoneal drainage with no
      drainage and no peritonization following radical hysterectomy and pelvic
      lymphadenectomy for invasive cervical cancer.
AB  - OBJECTIVE: To evaluate the postoperative morbidity and lymphocyst formation in
      invasive cervical cancer patients undergoing radical hysterectomy and pelvic
      lymphadenectomy (RHPL) with no drainage and no peritonization compared with
      retroperitoneal drainage and peritonization. METHODS: Between July 1999 and May
      2000, 100 patients with stage IA-IIA cervical cancer undergoing RHPL in Chiang
      Mai University Hospital were prospectively randomized to receive either no
      peritonization and no drainage (Group A = 48 cases) or retroperitoneal drainage
      and peritonization (Group B = 52 cases). Perioperative data and morbidity were
      recorded. Transabdominal and transvaginal sonography were performed at 4, 8 and
      12 weeks postoperatively to detect lymphocyst formation. RESULTS: Both groups
      were similar regarding age, size and gross appearance of tumor, tumor histology
      and stage. There was no difference between groups in respect of operative time,
      need for blood transfusion, intraoperative complications, hospital stay, number
      of nodes removed, nodal metastases, and need for adjuvant radiation and
      chemotherapy. Asymptomatic lymphocysts were sonographically detected at 4, 8 and
      12 weeks postoperatively in 3 (6.8%), 2 (4.6%), and 3 (7.7%) of 44, 43, and 39
      patients, respectively in Group A, whereas none was found in Group B (P = 0.2).
      No significant difference was found in term of postoperative morbidity in the two
      groups. CONCLUSION: Routine retroperitoneal drainage and peritonization after
      RHPL for invasive cervical cancer can be safely omitted.

PMID- 12214831
TI  - Loading dose versus standard regime of magnesium sulfate in the management of
      eclampsia: a randomized trial.
AB  - OBJECTIVE: To determine whether only loading dose of magnesium sulfate is
      effective in controlling convulsion in eclampsia. STUDY METHODS: This prospective
      study was conducted in Dhaka Medical College and Hospital, Bangladesh between
      July and November 1999. Eclamptic patients who were eligible for magnesium
      sulfate (MgSO4) therapy were randomly assigned by lottery to receive either only
      loading dose (n = 202) or standard regime (n = 199) of MgSO4. Besides the
      anticonvulsant, patients of both the groups were managed by same protocol for
      eclampsia management prepared by Eclampsia Working Group, Bangladesh. Efficacy of
      both the regimes was assessed by measuring the rate of recurrent convulsion.
      Results were expressed as mean +/- SD and a proportion. Statistical analysis was
      done using unpaired t-test, Z-test and chi2 test as appropriate. A P-value of <
      0.05 was considered significant. RESULTS: At the time of randomization there were
      no significant differences between the two groups in terms of age (22.40 +/- 4.21
      vs 22.49 +/- 4.67 years), parity (72.77% vs 70.35% primi), type of eclampsia
      (84.65% vs 85.42% antepartum eclampsia), number of convulsions (5.30 +/- 3.26 vs
      5.48 +/- 3.32 times), gestational age (35.65 +/- 3.37 vs 35.13 +/- 3.26 weeks),
      systolic blood pressure (153.19 +/- 20.19 vs 154.17 +/- 22.32 mmHg), diastolic
      blood pressure (106.23 +/- 13.84 vs 105.60 +/- 12.88 mmHg), proteinuria (70.80%
      vs 72.36% had > + proteinuria) and Glasgow Coma Scale (GCS) (73.26% vs 75.88% >
      8) for the loading and standard regime groups. There were also no differences
      between the two groups in mean fit and treatment interval (6.88 +/- 5.26 vs 7.12
      +/- 4.29h), fit and delivery interval (11.35 +/- 10.22 vs 11 +/- 6.69h) and
      return of consciousness (10.94 +/- 8.29 vs 11.24 +/- 8.37h). The recurrent
      convulsion rate was almost the same in both the groups (3.96% in loading vs 3.51%
      in standard regime, P > 0.05). Case fatality rate was 4.45% and 5.02% in loading
      and standard regime groups, respectively (P > 0.05). CONCLUSION: Only loading
      dose of MgSO4 can control convulsion in eclampsia and it is as effective as
      standard regime.

PMID- 12214832
TI  - Pregnancy with acute intermittent porphyria: a case report and review of
      literature.
AB  - Acute intermittent porphyria (AIP) is an inherited disorder characterized by
      partial defects in the heme biosynthetic pathway. Although its association with
      pregnancy is rare, it presents the obstetrician with challenging problems
      especially in labor management, as one of the obstetrical life line drugs
      (methergin) is contraindicated for use in these patients. We hereby present a
      case of AIP who had an uneventful pregnancy with a good neonatal outcome.

PMID- 12214833
TI  - Obstetric and perinatal outcome of women para > or = 5 including one lower
      segment cesarean section.
AB  - OBJECTIVE: To study the prevalence of antenatal, intrapartum and postnatal
      complications and their perinatal outcome in women who are delivering for the 6th
      time and have also had one cesarean section. METHODS: The records of all women
      para > or = 5 with one previous cesarean section (n = 238) delivered at King Fahd
      Hospital of the University between the January 1 1994 and December 31 2000 were
      reviewed and compared with women who delivered at the hospital in the year 2000
      (n = 2470). This data was analyzed for the peripartum and perinatal outcome.
      RESULTS: The incidence of malpresentation was higher in the study group. The
      incidence of uterine rupture and uterine scar dehiscence was significantly higher
      in the study group, but there was no perinatal or maternal death associated with
      this and in all cases the uterus was preserved. More women managed to deliver
      vaginally after the cesarean section in the grandmultiparous women compared with
      the women in the control group (81.5% vs 63.0%) P < 0.00006, where the cesarean
      section rate was significantly higher (P < 0.02). There were no significant
      differences in the incidences of preterm labor, lethal malformations, stillbirths
      and neonatal deaths in the two groups of women. There was one case of cesarean
      hysterectomy in each group due to placenta accreta and atonic postpartum
      hemorrhage, and one maternal death in the control group. CONCLUSION:
      Grandmultiparous women with one previous cesarean section have an increased risk
      of operative delivery, scar dehiscence, but there is no increase in perinatal or
      maternal mortality.

PMID- 12214834
TI  - Growing teratoma syndrome after chemotherapy for a mixed germ cell tumor of the
      ovary.
AB  - A retroperitoneal enlarging mass was detected and resected in a 24-year-old
      nulliparous woman after fertility-preserving surgery and adjuvant chemotherapy
      for a malignant germ cell tumor (MGCT) of the right ovary. This enlarging mass
      contained only a mature teratoma component. Alpha-fetoprotein, which was elevated
      to 21236.6 ng/mL before the initial surgery, persisted within normal after the
      completion of adjuvant platinum-based chemotherapy. The patient was diagnosed
      with growing teratoma syndrome. Growing teratoma syndrome originating from
      ovarian germ cell tumor is very rare. Only 15 cases have been reported. Surgical
      resection and histological confirmation of growing mass after MGCT treatment is
      essential before conducting salvage chemotherapy.

PMID- 12214835
TI  - Pneumomediastinum following esophageal rupture associated with hyperemesis
      gravidarum.
AB  - A patient was diagnosed with pneumomediastinum caused by an esophageal rupture
      during hyperemesis gravidarum. The woman, at 15 weeks' gestation, presented with
      hyperemesis gravidarum complicated by an episode of chest pain and disturbance of
      consciousness. Radiological examination revealed pneumomediastinum and
      subcutaneous emphysema. They are normally caused by either pulmonary or
      esophageal rupture. The esophageal etiology was suspected as more likely because
      of the severe vomiting accompanied with it. Although the clinical feature was
      quite complicated and esophageal rupture is generally a life-threatening disease,
      we chose conservative therapy which resulted in rapid recovery. The final
      diagnosis was confirmed by endoscopic examination performed after recovery.
      Pneumomediastinum during pregnancy is rare but it could be lethal. Careful and
      considerate assessments including surgical treatment should be necessary.

PMID- 12214836
TI  - Changes in endometrial wave-like movements in accordance with the phases of
      menstrual cycle.
AB  - OBJECTIVE: To investigate whether endometrial wave-like movements change with
      phases of the menstrual cycle. METHODS: Endometrial wave-like movements were
      observed by transvaginal sonographic tomography during 50 menstrual cycles of 20
      regularly menstruating women. RESULTS: Endometrial wave-like movements were not
      observed during the early follicular phase. These movements proceeded
      perpendicularly to the longitudinal uterine axis and appeared at the
      midfollicular phase. In the periovulatory phase, waves reached a peak and moved
      from cervix to fundus. In the postovulatory phase, endometrial wave-like
      movements became parallel to the longitudinal uterine axis. In the midluteal
      phase, most of these waves disappeared. Immediately before menstruation, the
      waves reappeared moving from fundus to cervix. These movements continued until
      day 1 of the subsequent menstrual phase. CONCLUSION: Endometrial wave-like
      movements change with the passage of menstrual cycle. They appear to play an
      important role in the transport of sperm and cervical mucus and the excretion of
      menstrual flow.

PMID- 12214837
TI  - Systematic review of randomized trials for the treatment of oral leukoplakia.
AB  - Oral leukoplakia is a relatively common oral lesion that, in a varying proportion
      of cases, undergoes malignant transformation. The aim of this review was to
      assess the effectiveness of treatments for leukoplakia. Randomized controlled
      trials (RCTs) enrolling patients with a diagnosis of oral leukoplakia were
      identified by searching biomedical databases, hand-searching relevant oral
      medicine journals, and contacting oral medicine experts through a European
      mailing list. The methodological quality of included studies was assessed on the
      basis of the method of allocation concealment, blindness of the study, and loss
      of participants. Data were analyzed by calculating relative risk. Malignant
      transformation of leukoplakia, demonstrated by histopathological examination, was
      the main outcome considered. Secondary outcomes included clinical resolution of
      the lesion and variation in dysplasia severity. Six RCTs were included in the
      review. Vitamin A and retinoids were tested in four RCTs; the other agents tested
      were bleomycin, mixed tea, and beta carotene. Malignant transformation was
      recorded in just two studies: none of the treatments tested showed a benefit when
      compared with placebo. Treatment with beta carotene and vitamin A or retinoids
      was associated with better rates of clinical remission, compared with placebo or
      absence of treatment. Whenever reported, a high rate of relapse was a common
      finding. Side effects of variable severity were often described; however,
      interventions were well accepted by patients since drop-out rates were similar
      between treatment and control groups. It is noteworthy that the possible
      effectiveness of surgical interventions, including laser therapy and cryotherapy,
      has apparently never been studied by means of an RCT. To date, in conclusion,
      there is no evidence of effective treatment in preventing malignant
      transformation of leukoplakia. Treatments may be effective in the resolution of
      lesion; however, relapses and adverse effects are common.

PMID- 12214838
TI  - Prevention of oral mucositis and oral candidiasis for patients with cancer
      treated with chemotherapy: cochrane systematic review.
AB  - The objectives of this study were to determine whether oral prophylactic agents
      are superior to placebo or no treatment on the incidence of oral mucositis and
      oral candidiasis for patients with cancer. A Cochrane systematic review was
      conducted of randomized trials of oral (and topical) prophylactic agents for
      mucositis and oral candidiasis, anywhere in the world, among patients with cancer
      (excluding head and neck) who were receiving chemotherapy. Eleven studies were
      included in the meta-analysis for mucositis. Of the six prophylactic agents used
      for mucositis, only one--ice chips--was effective (relative risk 0.57, 95% CI
      0.43 to 0.77). Fifteen studies were included in the meta-analysis for oral
      candidiasis. There is evidence that antifungal agents that are partially or fully
      absorbed from the gastrointestinal tract prevent oral candidiasis and that the
      partially absorbed agents may be more effective than the fully absorbed agents.
      The RR for partially absorbed agents was 0.13 (95% CI 0.06 to 0.27). In
      conclusion, there is weak and unreliable evidence that ice chips prevent
      mucositis. There is evidence that prophylactic use of antifungal agents, which
      are absorbed or partially absorbed from the gastrointestinal tract, reduce the
      clinical signs of oral candidiasis.

PMID- 12214839
TI  - The ADEA-NIDCR National Research Conference on putting science into practice: the
      critical role of dental schools.

PMID- 12214840
TI  - The role and importance of research and scholarship in dental education and
      practice.
AB  - Understanding the role and importance of research and scholarship in dental
      education and practice requires an appreciation of dentistry as a learned
      profession. A foundational attribute for the members of such a profession has to
      be sheer intellectual curiosity--a trait as important for the clinician as for
      the scientist. That improved patient care results from technical advances made
      possible through research is not seriously disputed by anyone. What is less
      apparent, however, is the role for research in the education of dentists and in
      the broader life of dental schools. Accosting this matter requires a distinction
      to be made between research and scholarship: while all research qualifies as
      scholarship, not all scholarship qualifies as research. Though the exact role of
      research in the educational process is open to debate, the importance of
      scholarship is not. An education colored by research is one way of achieving the
      intellectual rigor necessary for the professional. The key is cultivating in
      students a taste for complexity, for problems, and for problem solving. All
      dental schools without exception need to help students acquire this taste. In
      doing so, they will generate a few scientists; but, more importantly, they will
      create out of every graduate a man or woman of science. Only by becoming a person
      of science is there any hope that the practitioner will be able to acquire and
      assimilate new knowledge and to adapt to the changes in practice and in the
      profession that the future requires.

PMID- 12214841
TI  - Basic and clinical research: issues of cost, manpower needs, and infrastructure.

PMID- 12214842
TI  - Local, regional, and global partnerships in developing a research program.

PMID- 12214843
TI  - Gender differences in first-year dental students' motivation to attend dental
      school.
AB  - Women's role in the field of dentistry has historically been limited to the
      dental auxiliary fields, rather than that of D.D.S. or D.M.D. Today, women are
      nearly 38 percent of U.S. dental school students and 14 percent of active
      practitioners. The slow(er) influx of women into dentistry has been little
      studied by dental educators. During the 2000-01 academic year, we conducted a
      survey of first-year dental students at a sample of publicly funded U.S. dental
      schools. The purpose of the survey was to assess gender differences in motives
      for pursuing a dental career. The data show that male dental students rate self
      employment and business-related motives as more important, while female dental
      students rate people-oriented motives more highly. Factor analysis revealed four
      distinct clusters of motives for pursuing a dental career: a financial motive, a
      business-oriented motive, a people-oriented or caring motive, and a flexibility
      motive. Women scored significantly higher than men on the caring factor, whereas
      the reverse was true on the business factor. Male and female students rated
      financial and flexibility motives equally. The implications of the results for
      attracting students to the profession of dentistry are discussed.

PMID- 12214844
TI  - Angiogenesis in health and disease: insights into basic mechanisms and
      therapeutic opportunities.
AB  - Angiogenesis, the process that leads to the formation of new blood vessels or
      neovascularization, continues to be a topic of major scientific and public
      interest. As knowledge of the molecular mechanisms that regulate
      neovascularization continues to emerge, there is increasing hope that new
      discoveries will lead to newer therapies that target angiogenesis as a reliable
      option for disease therapy. For example, it may be possible to develop strategies
      that, on the one hand, are designed to limit angiogenesis for the treatment of
      chronic diseases such as cancer or rheumatoid arthritis and, on the other, to
      promote angiogenesis in the ischemic heart or diabetic limb. With the emergence
      of tissue engineering as a discipline, it has become increasingly clear that long
      term success in organ and tissue reconstruction will depend on the ability to
      develop a stable, renewable supply of blood vessels. In this review, I will
      provide a brief overview of this remarkably versatile biological response and
      discuss how recent discoveries in the field of angiogenesis have influenced the
      development of novel therapies, forced a reconsideration of conventional
      therapies, and revolutionized approaches to organ and tissue reconstruction.

PMID- 12214845
TI  - Information-seeking patterns of dentists in Istanbul, Turkey.
AB  - The authors surveyed dentists in Istanbul, Turkey to determine the modes they
      were using to access current professional information. A questionnaire was sent
      to 379 privately practicing dentists. The response rate was 35 percent. Privately
      practicing dentists frequently preferred to use traditional methods, such as
      discussions with colleagues, textbooks, and the brochures of products, to obtain
      information. Textbooks were found to be the most helpful information retrieval
      method. The lack of time after work and the difficulties in traffic in Istanbul
      were cited as the leading barriers to accessing information. We conclude that
      Turkish dentists in private practice need to improve their computer literacy
      skills in order to benefit from the generous opportunities that technology offers
      them and also to overcome the problem of professional isolation in their lives.

PMID- 12214846
TI  - Interactions of cationic drugs and cardiac glycosides at the hepatic uptake
      level: studies in the rat in vivo, isolated perfused rat liver, isolated rat
      hepatocytes and oocytes expressing oatp2.
AB  - This paper deals with a crucial mechanism for interaction of basic drugs and
      cardiac glycosides at the hepatic uptake level. Available literature data is
      provided and new material is presented to picture the differential transport
      inhibition of bulky (type2) cationic drugs by a number of cardiac glycosides in
      rat liver. It is shown that the so called organic anion transporting peptide 2
      (oatp2) is the likely interaction site: differential inhibition patterns as
      observed in oocytes expressing oatp2, could be clearly identified also in
      isolated rat hepatocytes, isolated perfused rat liver and the rat in vivo. The
      anticipation of transport interactions at the hepatic clearance level should be
      based on data on the relative affinities of interacting substrates for the
      transport systems involved along with knowledge on the pharmacokinetics of these
      agents as well as the chosen dose regimen in the studied species. This review
      highlights the importance of multispecific tranporter systems such as OATP,
      accommodating a broad spectrum of organic compounds of various charge, implying
      potential transport interactions that can affect body distribution and organ
      clearance.

PMID- 12214847
TI  - Design and synthesis of isoindoloquinoline derivatives as potential antitumor
      agents.
AB  - A series of isoindoloquinoline derivatives was synthesized and evaluated in vitro
      cytotoxicity against four human cancer cell lines (HCT15, SK-OV-3, MDA-MB-468 and
      T-47D).

PMID- 12214848
TI  - Recognition of the importance of imidazolidinone motif for cytotoxicity of 4
      phenyl-1-arylsulfonylimidazolidinones using thiadiazolidine-1,1-dioxide analogs.
AB  - For probing the importance of planarity of imidazolidinone motif of 4-phenyl-1-(N
      acylindoline-5-sulfonyl)imidazolidinones for their cytotoxicity, 4-phenyl-1-(N
      acylindoline-5-sulfonyl)[1,2,5]thiadiazolidine-1,1-dioxides 2 were prepared and
      their cytotoxicity were measured against human lung carcinoma (A549), human colon
      carcinoma (COL0205), human ovarian cancer (SK-OV-3), human leukemic cancer
      (K562), and murine colon adenocarcinoma (Colon26) cell lines in vitro. Although
      only carbonyl moiety of imidazolidinone ring was replaced with sulfonyl group,
      compounds 2 do not show any activity against all five cancer cell lines unlike 1.
      Therefore the planarity of imidazolidinone ring of 1 should be an important
      factor for their cytotoxic activity.

PMID- 12214849
TI  - Three new dammarane glycosides from heat processed ginseng.
AB  - Three new dammarane glycosides were isolated from the processed ginseng (SG; Sun
      Ginseng). Their structure were determined to be 3beta,12beta-dihydroxydammar
      20(21),24-diene-3-O-beta-D-glucopyranosyl(1 --> 2)-beta-D-glucopyranoside;
      3beta,12beta-dihydroxydammar-20(21),24-diene-3-O-beta-D- glucopyranoside and
      3beta,6alpha,12beta-trihydroxydammar-20(21),24-diene-6-O-beta-D-glucopyranoside
      based on spectroscopic evidences. The compounds were named as ginsenoside Rk1,
      Rk2, and Rk3 respectively.

PMID- 12214850
TI  - A new phenolic amide from Lycium chinense Miller.
AB  - A new phenolic amide, dihydro-N-caffeoyltyramine (1) was isolated from the root
      bark of Lycium chinense Miller, along with known compounds, trans-N
      caffeoyltyramine (2), cis-N-caffeoyltyramine (3), and lyoniresinol 3alpha-O-beta
      D-glucopyranoside (4). Their structures were determined by spectroscopic
      analysis. A NBT superoxide scavenging assay revealed that three phenolic amides
      showed potent antioxidative activity.

PMID- 12214851
TI  - 13-Hydroxy-9Z,11E,15E-octadecatrienoic acid from the leaves of Cucurbita
      moschata.
AB  - A new unsaturated hydroxy fatty acid was isolated from the leaves of Cucurbita
      moschata through repeated silica gel column chromatography and chemical methods.
      The structure of the new fatty acid was determined as 13-hydroxy-9,11,15
      octadecatrienoic acid on the basis of several spectral data including 2D-NMR. The
      stererostructures of double bonds were determined to be 9Z, 11E and 15E by
      coupling patterns of related proton signals in the 1H-NMR and NOESY experiments.

PMID- 12214852
TI  - Anti-human immunodeficiency virus-type 1 activity of constituents from Juglans
      mandshurica.
AB  - Three naphthalene glycosides (1-3), four flavonoids (4-7), and two galloyl
      glycosides (8-9) were isolated from the stem-bark of Juglans mandshurica
      (Juglandaceae). Their structures were determined by chemical and spectral means,
      including to 2D-NMR (COSY, HMQC, and HMBC) experiments. Amongst the isolated
      compounds, taxifolin (4) showed the most potent HIV-induced cytopethic activity
      against MT-4 cells with complete inhibitory concentration (IC100) value of 25
      microg/ml and maximum cytotoxic concentration (CC100) value of above 100
      microg/ml. However, naphthalene glycosides (1-3), flavonoids (5-7), and galloyl
      tannins (8-9) were inactive against anti-HIV-1 activity.

PMID- 12214853
TI  - Inhibitory activity of diacylglycerol acyltransferase by tanshinones from the
      root of Salvia miltiorrhiza.
AB  - The inhibitory activity of tanshinones from Salvia miltiorrhiza was tested on rat
      liver diacylglycerol acyltransferase (DGAT). Cryptotanshinone (1) and 15,16
      dihydrotanshinone I (3) exhibited potent DGAT inhibitory activities dose
      dependently with IC50 values of 10.5 microg/ml and 11.1 microg/ml. However,
      tanshinone IIA (2) and tanshinone I (4) showed very weak inhibition (IC50 value:
      > 250 microg/ml). A dihydrofuran moiety was seemed to be responsible for the
      stronger inhibitory activity.

PMID- 12214854
TI  - Free radical scavengers from the heartwood of Juniperus chinensis.
AB  - The antioxidant activity of Juniperus chinensis (Cupressaceae) was determined by
      measuring the radical scavenging effect on DPPH (1,1-diphenyl-2-picrylhydrazyl).
      The methanolic extract of J. chinensis heartwood showed the strong antioxidant
      activity. The antioxidant activity of n-BuOH soluble fraction was stronger than
      that of the others, and the fraction was subjected to purification by repeated
      silica gel and Sephadex LH-20 column chromatography. Quercetin, naringenin,
      taxifolin, aromadendrin and isoquercitrin were isolated from the n-BuOH fraction.
      Their structures were elucidated by physico-chemical and spectroscopic studies.

PMID- 12214855
TI  - Development of quantitative extraction method of amygdalin without enzymatic
      hydrolysis from tonin(Persicae Semen) by high performance liquid chromatography.
AB  - Tonin(Persicae Semen) is the herb medicine that contains amygdalin as a major
      ingredient. Amygdalin in water is decomposed into benzaldehyde, HCN, and glucose
      by emulsin, a hydrolysis enzyme in tonin. A useful and practical method for the
      optimum extraction condition of amygdalin without enzymatic hydrolysis is
      required. The extraction yield of amygdalin of natural formula tonin was 0.1%
      from crude powders, 1.4% from small pieces, 3.5% from half pieces and 2.4% from
      whole pieces. The extraction yield of amygdalin of outer shell-eliminated tonin
      was 0.3% from crude powders, 1.4% from small pieces, and 3.5% from half pieces
      and whole pieces respectively. The extraction yield of amygdalin was most high
      when using the size larger than half.

PMID- 12214856
TI  - Augmentation of macrophage antitumor activities and nitric oxide production by
      oregonin.
AB  - Oregonin, a diarylheptanoid derivative from Alnus hirsuta Turcz, Betulaceae, was
      evaluated for its antitumor activity. Oregonin, known to have an antitumor
      function, and is a novel immunomodulator, which may augment macrophage activity.
      MTT assays and NO production tests were performed in order to investigate the
      cytotoxicity of oregonin in tumor cells and to examine its influence on
      macrophage in detail. In this study, the tumoricidal activity was also evaluated
      by a MTT assay. The cytotoxicity measurements in the oregonin-treated group both
      in vitro and in vivo showed a significant difference from that of the control
      group. In vivo, oregonin significantly increased NO production in a dose
      dependent manner, and in vitro, the thioglycolate-induced inflammatory
      macrophages increased NO production in a dose-dependent manner after incubation.
      These results suggest that oregonin reacts with both the inflammatory and non
      inflammatory macrophages in a similar way.

PMID- 12214857
TI  - Oligosaccharide-linked acyl carrier protein, a novel transmethylase inhibitor,
      from porcine liver inhibits cell growth.
AB  - We have previously reported on the identification of the endogenous
      transmethylation inhibitor oligosaccharide-linked acyl carrier protein (O-ACP).
      In this study, the role of the transmethylation reaction on cell cycle
      progression was evaluated using various transmethylase inhibitors, including O
      ACP. O-ACP significantly inhibited the growth of various cancer cell lines,
      including NIH3T3, ras-transformed NIH3T3, MDA-MB-231, HT-1376, and AGS. In
      addition, exposure of ras-transformed NIH3T3 to O-ACP caused cell cycle arrest at
      the G0/G1 phase, which led to a decrease in cells at the S phase, as determined
      by flow cytometry. In contrast, transmethylase inhibitors did not affect the
      expression of p21(WAF1/Cip1), a well known inhibitor of cyclin dependent kinase,
      indicating that the cell cycle arrest by transmethylase inhibitors might be
      mediated by a p21(WAF1/Cip1)-independent mechanism. Therefore, O-ACP, a novel
      transmethylase inhibitor, could be a useful tool for elucidating the novel role
      of methylation in cell proliferation and cell cycle progression.

PMID- 12214858
TI  - Effects of the chestnut inner shell extract on the expression of adhesion
      molecules, fibronectin and vitronectin, of skin fibroblasts in culture.
AB  - The inner shell of the chestnut (Castanea crenata S. et Z., Fagaceae) has been
      used as an anti-wrinkle/skin firming agent in East Asia, and preliminary
      experiments have found that a 70% ethanol extract from this plant material can
      prevent cell detachment of skin fibroblasts from culture plates. In order to
      examine the molecular mechanisms underlying this phenomenon, its effects on the
      expression of adhesion molecules, such as fibronectin and vitronectin, were
      investigated using the mouse skin fibroblast cell line, NIH/3T3. Using fixed-cell
      ELISA, Western blotting and immunofluorescence cell staining, it was clearly
      demonstrated that the chestnut inner shell extract enhanced the expression of the
      cell-associated fibronectin and vitronectin. Scoparone (6,7-dimethoxycoumarin),
      isolated from the extract, also possessed similar properties. These findings
      suggest that the enhanced expression of the adhesion molecules may be one of the
      molecular mechanisms for how the chestnut inner shell extract preventing cell
      detachment and may be also responsible for its anti-wrinkle/skin firming effect.

PMID- 12214859
TI  - Suppression of phorbol ester-induced NF-kappaB activation by capsaicin in
      cultured human promyelocytic leukemia cells.
AB  - Capsaicin, a major pungent constituent of red pepper (Capsicum annuum L.)
      possesses a vast variety of pharmacologic and physiologic activities. Despite its
      irritant properties, the compound exerts anti-inflammatory and anti-nociceptive
      effects. Previous studies from this laboratory revealed that capsaicin, when
      topically applied onto dorsal skin of female ICR mice, strongly attenuated
      activation of NF-kappaB and AP-1 induced by the typical tumor promoter, 12-O
      tetradecanoylphorbol-13-acetate (TPA), which may account for its anti-tumor
      promoting activity in mouse skin. In the present work, we have found that
      capsaicin suppresses TPA-stimulated activation of NF-kappaB through inhibition of
      IkappaB alpha degradation and blockade of subsequent nuclear translocation of p65
      in human promyelocytic leukemia HL-60 cells. Methylation of the phenolic hydroxyl
      group of capsaicin abolished its inhibitory effect on NF-kappaB DNA binding.
      Likewise, TPA-induced activation of AP-1 was mitigated by capsaicin treatment.

PMID- 12214860
TI  - Costunolide induces differentiation of human leukemia HL-60 cells.
AB  - Costunolide has been reported to be a cytotoxic and chemopreventive agent. This
      work investigated the mechanism of the antiproliferative effect of costunolide
      and determined that it induced differentiation of the human leukemia cell line HL
      60. Costunolide exhibited a potent antiproliferative activity against HL-60
      cells. It was also found to be a potent inducer of differentiation in human
      leukemia derived HL-60 cells through the examination of differentiation markers,
      as assessed by the reduction of nitroblue-tetrazolium, the increase in esterase
      activities and phagocytic activity, morphology change and the expression of CD14
      and CD66b surface antigens. These results, accompanied by a decline in the
      expression of c-myc protein, suggest that costunolide induces differentiation of
      human leukemia cells to granulocytes and monocytes/macrophages lineage.

PMID- 12214862
TI  - Enhancement of NK cytotoxicity, antimetastasis and elongation effect of survival
      time in B16-F10 melanoma cells by oregonin.
AB  - We investigated the antitumor activity of oregonin, a diarylheptanoid derivative
      purified from Alnus hirsuta Turcz, Betulaceae. Oregonin is a potential novel
      immunomodulator, which augments the activation of natural killer (NK) cells, and
      thereby leads to a powerful antitumor activity. To evaluate the cytotoxicity of
      oregonin against tumor cells, we examined the effectiveness of NK cells and
      determined that oregonin could increase NK cell cytotoxicity. This was confirmed
      by MTT assay. In addition, the survival time of C57BL/6 mice were measured by
      inoculating B16-F10 melanoma cells to mice via intra muscular (i.m.) injection.
      Oregonin treatment after 10 hours of inoculation at 10 mg/kg dosage showed a
      significant extension of survival time by up to 51.32%, when compared to the
      control group. Moreover, oregonin significantly reduced the incidence of
      pulmonary metastasis, which may be developed from B16-F10 melanoma cells. These
      findings suggest that oregonin may be classified as a new and novel
      immunomodulator due to its potential antitumor activity.

PMID- 12214861
TI  - Role of protein disulfide isomerase in molecular fate of thyroglobulin and its
      regulation by endogenous oxidants and reductants.
AB  - The molecular fate of thyroglobulin (Tg) is controlled by oligomerization, a
      means of storing Tg at high concentrations, and deoligomerization. The
      oligomerization of bovine Tg are intermolecular reactions that occur through
      oxidative processes, such as disulfide and dityrosine formation, as well as
      isopeptide formation; disulfide formation is primarily responsible for Tg
      oligomerization. Here, the protein disulfide isomerase (PDI) and/or peroxidase
      induced oligomerization of unfolded thyroglobulins, which were prepared by
      treating bovine Tg with heat, urea or thiol/urea, was investigated using SDS-PAGE
      analyses. In addition, the enzymatic oligomerization was compared with non
      enzymatic oligomerization. The thermally-induced oilgomerization of Tg, dependent
      on glutathione redox state, was affected by the ionic strength or the presence of
      a surfactant. Meanwhile, PDI-catalyzed oligomerization, time and pH-dependent,
      was the most remarkable with unfolded/reduced Tg, which was prepared from a
      treatment with urea/DTT, while the thermally-unfolded Tg was less sensitive.
      Similarly, the oligomerization of unfolded/reduced Tg was also mediated by
      peroxidase. However, PDI showed no remarkable effect on the peroxidase-mediated
      oligomerization of either the unfolded or unfolded/reduced Tg. Additionally, the
      reductive deoligomerization of oligomeric Tg was exerted by PDI in an excessively
      reducing state. Based on these results, it is proposed that PDI catalyzes the
      oligomerization of Tg through the disulfide linkage and its deoligomerization in
      the molecular fate, and this process may require a specific molecular form of Tg,
      optimally unfolded/reduced, in a proper redox state.

PMID- 12214864
TI  - An improved, reliable and practical kinetic assay for the detection of
      prekallikrein activator in blood products.
AB  - An improved kinetic assay for prekallikrein activator (PKA), a potential
      vasodilator, has been developed to be used as an indicator for quality control
      during production of human albumin preparations. It consists of two reaction
      stages. In the first stage, PKA and prekallikrein are incubated at 37 degrees C
      for 45 min to allow the transformation into kallikrein. Kallikrein, a serine
      protease, catalyzes the splitting of p-nitroaniline (pNA) from its substrate H-D
      Pro-Phe-Arg-pNA (S-2302). The rate at which pNA is released was measured
      spectrophotometrically at 405 nm. Prekallikrein, a substrate of PKA was purified
      by DEAE ion-exchange chromatography and the major potential variations in the
      assay were optimized; pH 8.0 and 150 mM sodium chloride were chosen to give a
      proper ionic strength. Reaction times in the range of 10 to 360 min provided
      linear dose-response curves. The concentration of prekallikrein was adjusted to
      fall between 1:1 and 1:3 dilutions to generate a linear standard calibration
      curve. Under the optimized conditions, reproducibility was checked. In a
      precision test, the coefficient of variation (CV) stayed within +/-4% and the
      dose-response curve showed a good correlation (r2=0.999). An accuracy test with
      an international standard of PKA afforded a mean recovery of 97.5%.

PMID- 12214863
TI  - Inhibition of angiogenesis by propolis.
AB  - Propolis, obtained from honeybee hives, has been used in Oriental folk medicine
      as an anti-inflammatory, anti-carcinogenic, and immunomodulatory agent. There is
      considerable evidence suggesting that angiogenesis and chronic inflammation are
      codependent. Blockage of angiogenesis results in an anti-inflammatory effect.
      Ethanol (EEP) and ether extracts of propolis (REP), and caffeic acid phenethyl
      ester (CAPE), an active component of propolis, were examined for their anti
      angiogenic activities using the chick embryo chorioallantoic membrane (CAM), and
      the calf pulmonary arterial endothelial (CPAE) cell proliferation, assays. The
      presence of EEP, REP and CAPE inhibited angiogenesis in the CAM assay and the
      proliferation of CPAE cells. The results suggest that anti-angiogenic activities
      of EEP, REP and CAPE are also responsible for their anti-inflammatory effect.

PMID- 12214865
TI  - Inhibitory mechanism of bromocriptine on catecholamine release evoked by
      cholinergic stimulation and membrane depolarization from the rat adrenal medulla.
AB  - The purpose of this study was to determine whether bromocriptine affects the
      catecholamines (CA) secretion evoked in isolated perfused rat adrenal glands, by
      cholinergic stimulation, membrane depolarization and calcium mobilization, and to
      establish the mechanism of its action. The perfusion of bromocriptine (1-10
      microM) into an adrenal vein, for 60 min, produced relatively dose-dependent
      inhibition in the secretion of catecholamines (CA) evoked by acetylcholine (ACh,
      5.32 mM), DMPP (100 microM for 2 min), McN-A-343 (100 microM for 2 min),
      cyclopiazonic acid (CPA, 10 microM for 4 min) and Bay-K-8644 (10 microM for 4
      min). High K+ (56 mM)-evoked CA release was also inhibited, although not in a
      dose-dependent fashion. Also, in the presence of apomorphine (100 microM), which
      is also known to be a selective D2-agonist, the CA secretory responses evoked by
      ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also
      significantly depressed. However, in adrenal glands preloaded with bromocriptine
      (3 microM) in the presence of metoclopramide (15 microM), a selective D2
      antagonist, the CA secretory responses evoked by ACh, high potassium, DMPP, McN-A
      343, Bay-K-8644 and cyclopiazonic acid considerably recovered as compared to that
      of bromocriptine only. Taken together, these results suggest that bromocriptine
      can inhibit the CA secretion evoked by stimulation of cholinergic receptors, as
      well as by membrane depolarization, in the perfused rat adrenal medulla. It is
      thought this inhibitory effect of bromocriptine may be mediated by inhibiting the
      influx of extracellular calcium and the release from intracellular calcium
      stores, through the activation of dopaminergic D2-receptors located in the rat
      adrenomedullary chromaffin cells. Furthermore, these findings also suggest that
      the dopaminergic D2-receptors may play an important role in regulating
      adrenomedullary CA secretion.

PMID- 12214866
TI  - Inhibitory effect of BCG cell-wall skeletons (BCG-CWS) emulsified in squalane on
      tumor growth and metastasis in mice.
AB  - The antimetastatic effect of BCG-CWS, which was emulsified in an oil-in-water
      form with either Drakeol 6VR mineral oil (BCG-CWS/DK) or squalane (BCG-CWS/SQA),
      on lung metastasis produced by highly metastatic murine tumor cells, Colon26-M3.1
      carcinoma cells and B16-BL6 melanoma cells, was investigated in syngeneic mice.
      An intravenous (i.v.) administration of BCG-CWS (100 mg/mouse) 1 day after tumor
      inoculation significantly inhibited tumor metastasis of both Colon26-M3.1
      carcinoma and B16-BL6 melanoma cells in experimental lung metastasis models. No
      differences in the antitumor activity of the two oil-based formulations (BCG
      CWS/DK and BCG-CWS/SQA) were obverved. However, BCG-CWS/SQA administered through
      subcutaneous (s.c.) route was shown to be effective only when it was
      consecutively injected (3 times) after tumor inoculation. An in vivo analysis for
      tumor-induced angiogenesis showed that a single i.v. administration of BCG
      CWS/SQA inhibited the number of tumor-induced blood vessels and suppressed tumor
      growth. Furthermore, the multiple administration of BCG-CWS/SQA given at on week
      intervals led to a significant reduction in spontaneous lung metastasis of B16
      BL6 melanoma cells in a spontaneous metastasis model. These results suggest that
      BCG-CWS emulsified with squalane is a potent inhibitory agent of lung metastasis,
      and that the antimetastatic effect of BCG-CWS is related to the suppression of
      tumor growth and the inhibition of tumor-induced angiogenesis.

PMID- 12214867
TI  - Antithrombotic and antiallergic activities of rhaponticin from Rhei Rhizoma are
      activated by human intestinal bacteria.
AB  - To evaluate the antithrombotic and antiallergic properties of rhaponticin
      extracted from Rhei Rhizoma, the in vitro and ex vivo inhibitory activities of
      rhaponticin and its metabolite, rhapontigenin, were measured. These compounds
      inhibited in vitro ADP- and collagen-induced platelet aggregation. Rhapontigenin
      was more potent, with IC50 values of 4 and 70 microg/ml, respectively. In ex vivo
      ADP- and collagen-induced rat platelet aggregation, these compounds also
      exhibited a potent inhibitory effect. The antiplatelet aggregation effects of
      rhaponticin and rhapontigenin were more potent than those of aspirin.
      Rhapontigenin showed significant protection from death due to pulmonary
      thrombosis in mice. Rhapontigenin also showed the strongest inhibitory activity
      against beta-hexosaminidase release induced by DNP-BSA. These compounds inhibited
      PCA reaction in mice. Rhapontigenin intraperitoneally administered showed the
      strongest inhibitory activity and significantly inhibited PCA at doses of 25 and
      50 mg/kg, with inhibitory activities of 48 and 85%, respectively. The inhibitory
      activity of orally administered rhaponticin was stronger than that of
      intraperitoneally administered rhaponticin. These results suggest that
      rhaponticin, in the rhizome of Rhei Rhizoma, is a prodrug that has extensive
      antiallergic and antithrombotic properties.

PMID- 12214868
TI  - Preparation and evaluation of aceclofenac microemulsion for transdermal delivery
      system.
AB  - To develop novel transdermal formulation for aceclofenac, microemulsion was
      prepared for increasing its skin permeability. Based on solubility and phase
      studies, oil and surfactant was selected and composition was determined.
      Microemulsion was spontaneously prepared by mixing ingredients and the
      physicochemical properties such was investigated. The mean diameters of
      microemulsion were approximately 90 nm and the system was physically stable at
      room temperature at least for 3 months. In addition, the in vitro and in vivo
      performance of microemulsion formulation was evaluated. Aceclofenac was released
      from microemulsion in acidic aqueous medium, and dissolved amounts of aceclofenac
      was approximately 30% after 240 min. Skin permeation of aceclofenac from
      microemulsion formulation was higher than that of cream. Following transdermal
      application of aceclofenac preparation to delayed onset muscle soreness, serum
      creatine phosphokinase and lactate dehydrogenase activity was significantly
      reduced by aceclofenac. Aceclofenac in microemulsion was more potent than cream
      in the alleviation of muscle pain. Therefore, the microemulsion formulation of
      aceclofenac appear to be a reasonable transdermal delivery system of the drug
      with enhanced skin permeability and efficacy for the treatment of muscle damage.

PMID- 12214869
TI  - Pharmacokinetics of acebutolol and its main metabolite, diacetolol after oral
      administration of acebutolol in rabbits with carbon tetrachloride-induced hepatic
      failure.
AB  - Pharmacokinetic characteristics of acebutolol and its main metabolite,
      diacetolol, following a single 10 mg/kg oral dose, were investigated in rabbits
      with carbon tetrachloride-induced hepatic failure. Plasma concentrations of
      acebutolol and diacetolol were determined by a high performance liquid
      chromatography assay. The area under the plasma concentration-time curves (AUC)
      and maximum plasma concentration (Cmax) of acebutolol were significantly
      increased in moderate and severe carbon tetrachloride-induced hepatic failure
      rabbits. The ratio of the diacetolol to total acebutolol in plasma (i.e.,
      metabolite percentage rate) was significantly decreased in moderate and severe
      carbon tetrachloride-induced hepatic failure rabbits. Volume of distribution (Vd)
      and total body clearance (CL1) of acebutolol were significantly decreased in
      moderate and severe carbon tetrachloride-induced hepatic failure rabbits. Slope
      of terminal phase (beta) of acebutolol was significantly decreased in hepatic
      failure rabbits. These findings suggest that the Vd, CL1 and beta of acebutolol
      were significantly decreased as a result of inhibition of the hepatic metabolism
      in moderate to severe hepatic failure rabbits. Therefore, dose adjustment may be
      necessary for acebutolol in hypertensive patients with hepatic damage.

PMID- 12214870
TI  - The effect of storage conditions on the permeability of porcine buccal mucosa.
AB  - The impact of storage conditions on the permeability of porcine buccal mucosa to
      [3H]water and [14C]mannitol was assessed. The fresh porcine buccal tissue (fresh
      tissue) was obtained by utilizing pig heads within 24 hours of slaughter. The
      stored and frozen porcine buccal tissues (stored tissue and frozen tissue) were
      obtained after the storage of the tissue intact in the pig heads at 4 degrees C
      or -20 degrees C, respectively, for 24 h. The results demonstrated that the
      barrier properties of the porcine buccal mucosa were maintained with regard to
      [3H]water permeability when stored at 4 degrees C for 24 h. However, freezing the
      tissue resulted in tissue damage illustrated by a significant increase in
      [3H]water permeability. [14C]Mannitol does not appear to be a suitable model
      solute to assess the ex vivo permeability of porcine buccal mucosa due to its
      extremely low permeability.

PMID- 12214871
TI  - Which dosing scheme is suitable for the taxanes? An in vitro model.
AB  - The discovery and development of the taxane class of antitumor compounds
      represent significant advances in the treatment of patients with a variety of
      malignancies. These drugs are effectively used in the treatment of breast cancer.
      In this study we evaluated the efficacy of fractionated usage of both paclitaxel
      and docetaxel as a single agent in the breast cancer cell line MCF-7. It has been
      shown that the cytotoxic effect of paclitaxel was increased when the divided IC50
      concentrations were used sequentially and in contrast to paclitaxel, cytotoxic
      effect of docetaxel was decreased with the same schema and the single dose of
      IC50 concentration was optimal. The cause of the difference between the cytotoxic
      effects of two agents with this schedule is obscure. Demonstrating mechanisms,
      which are responsible for these differences, will be important for more rational
      use of taxoids and to provide basis for the following clinical trials.

PMID- 12214872
TI  - Effect of crystal form on in vivo topical anti-inflammatory activity of
      corticosteroids.
AB  - The aim of this study was to gain information on the effects of the crystal form
      of corticosteroids on the topical anti-inflammatory activity. Two different
      crystal forms, Form A and Form B, of the drugs of prednicarbate, hydrocortisone,
      betamethasone 17-valerate, prednisolone, and methyl prednisolone were prepared
      and their topical anti-inflammatory activities were measured using arachidonic
      acid induced ear edema assay in mice. Two crystal forms of the drugs showed
      differences in anti-inflammatory activity. Among the drugs examined, Form B of
      prednicarbate and betamethasone 17-valerate showed significantly more potent anti
      inflammatory activities as compared to their Form A.

PMID- 12214873
TI  - Contact flexible microstrip applicators (CFMA) in a range from microwaves up to
      short waves.
AB  - Contact flexible microstrip applicator (CFMA) is a new light-weight microstrip
      applicator type for superficial and deep local hyperthermia. Typical specimens
      are developed for operation at frequencies of 434, 70, 40, and 27 MHz. The main
      common features of CFMA, namely, their flexibility and light weight, as well as
      their aperture dimensions slightly depend on the operating frequency. Two antenna
      types are used in CFMAs: inductive antennas with a radiating plane electrical
      dipole at microwaves, and coplanar capacitive antennas, providing depression of
      the normal component of the electrical field in the very high-frequency (VHF) and
      high-frequency (HF) range. The flexibility of the applicators enables one to
      conform them with curved surfaces. In a bent state of the applicators there
      arises a focusing effect of energy deposition in deeper located tissues due to
      linear polarization of the irradiated electromagnetic (EM) field, inherent in
      CFMA. All CFMA are integrated with silicon water boluses which serve as a
      matching element, so as a skin cooling agent. Due to this and to the predominance
      of the tangential electrical component in the radiated EM field, no fat
      overheating effects are noticed, as a rule. The aperture of the developed
      applicators overlap the range 160-630 cm2 providing effective heating field sizes
      (EFSs) 64-400 cm2, respectively. The most bulky CFMAs with an aperture of (21 x
      29) cm2 operating at the frequency of 434 MHz weigh 0.8 kg and 2.5 kg at 27 MHz.
      Phenomenological analysis of the radiating systems, as well as experimental
      evaluation of the applicators are presented. CFMAs operating at frequencies of
      434 and 40 MHz are used in clinical practice. CFMA at 70 and 27 MHz are subjected
      to laboratory clinical investigations.

PMID- 12214874
TI  - An inverse design of an open, head/neck RF coil for MRI.
AB  - Radio-frequency (RF) coils are a necessary component of magnetic resonance
      imaging (MRI) systems. When used in transmit operation, they act to generate a
      homogeneous RF magnetic field within a volume of interest and when in receive
      operation, they act to receive the nuclear magnetic resonance signal from the RF
      excited specimen. This paper outlines a procedure for the design of open RF coils
      using the time-harmonic inverse method. This method entails the calculation of an
      ideal current density on a multipaned planar surface that would generate a
      specified magnetic field within the volume of interest. Because of the averaging
      effect of the regularization technique in the matrix solution, the specified
      magnetic field is shaped within an iterative procedure until the generated
      magnetic field matches the desired magnetic field. The stream-function technique
      is used to ascertain conductor positions and a method of moments package is then
      used to finalize the design. An open head/neck coil was designed to operate in a
      clinical 2T MRI system and the presented results prove the efficacy of this
      design methodology.

PMID- 12214875
TI  - Decomposition of field-induced transmembrane potential responses of single
      cardiac cells.
AB  - In this study, we used a multi-site optical mapping system to record field
      induced responses of single cells isolated from guinea pig hearts. The cells were
      stained with voltage sensitive dye di-8-ANEPPS and stimulated with two uniform
      field (S1-S2) pulses along their longitudinal axes. The first pulse (S1 = 5 ms,
      <10 V/cm) was applied during rest and elicited an action potential. The second
      pulse (S2 = 10 ms, 4-50 V/cm) was applied 15 ms after the break of the S1 pulse
      (during the action potential plateau). The transmembrane potential responses,
      Vm(F)s, were optically recorded from up to 12 sites along the cell length using a
      fiber optic based optical mapping system at a resolution of 17 or 25 microm. The
      field-induced Vm(F)s had a complex spatio-temporal pattern. We show that these
      responses can be decomposed into simpler components. The first component, termed
      the differential-mode component (Vmd(F)), is like the response of a passive cell.
      The second component, termed the common-mode component (Vmc(F)), is identical all
      along the cell and adds a constant offset to the differential mode response of
      various sites along the cell length, to produce the total Vm(F) responses of the
      cell.

PMID- 12214876
TI  - Narrowband auscultatory blood pressure measurement.
AB  - Auscultatory blood pressure measurement uses the presence and absence of acoustic
      pulses generated by an artery (i.e., Korotkoff sound), detected with a
      stethoscope or a sensitive microphone, to noninvasively estimate systolic and
      diastolic pressures. Unfortunately, in high noise situations, such as ambulatory
      environments or when the patient moves moderately, the current auscultatory blood
      pressure method is unreliable, if at all possible. Empirical evidence suggests
      that the pulse beneath an artery occlusion travels relatively slow compared with
      the speed of sound. By placing two microphones along the bicep muscle near the
      brachial artery under the occlusion cuff, a similar blood pressure pulse appears
      in the two microphones with a relative time delay. The acoustic noise, on the
      other hand, appears in both microphones simultaneously. The contribution of this
      paper is to utilize this phenomenon by filtering the microphone waveforms to
      create spatially narrowband information signals. With a narrowband signal, the
      microphone signal phasing information is adequate for distinguishing between
      acoustic noise and the blood pressure pulse. By choosing the microphone spacing
      correctly, subtraction of the two signals will enhance the information signal and
      cancel the noise signal. The general spacing problem is also presented.

PMID- 12214877
TI  - Signal strength versus cuff length in nerve cuff electrode recordings.
AB  - When a nerve cuff electrode is used for the recording of signals from peripheral
      nerves, cuff dimensions have to be chosen. Traditionally, the peak-to-peak
      amplitude of the single-fiber action potential (SFAP) is optimized through the
      choice of cuff diameter and cuff length. In this paper, the dependency of the
      root-mean-square (RMS) value of the nerve signal on the cuff dimensions was
      studied and compared with the peak-to-peak value of the SFAP. A simple
      approximation for signal optimization by cuff dimensioning is suggested. The
      results were obtained from modeled SFAPs and from the electroneurogram (ENG)
      created by superimposed SFAPs, obtained from an inhomogeneous volume conductor
      model. The results show that the RMS value of the nerve signal is considerably
      more sensitive to the cuff length than the SFAP peak-to-peak amplitude, and that
      the RMS of the ENG is a linear function of the fiber diameter.

PMID- 12214878
TI  - Averaging over depth during optical mapping of unipolar stimulation.
AB  - Numerical simulations have predicted the distribution of transmembrane potential
      during electrical stimulation of cardiac tissue. When comparing these predictions
      to measurements obtained using optical mapping techniques, the optical signal
      should not be compared to the transmembrane potential calculated at the surface
      of the tissue, but instead to the transmembrane potential averaged over depth. In
      this paper, the bidomain model is used to calculate the transmembrane potential
      in a three-dimensional slab of cardiac tissue, stimulated by a unipolar electrode
      on the tissue surface. For an optical decay constant of 0.3 mm and an electrode
      radius of 1 mm, the surface transmembrane potential is more than a factor of
      three larger than the transmembrane potential averaged over depth. Our results
      suggest that optical mapping underestimates the surface transmembrane potential
      during electrical stimulation.

PMID- 12214879
TI  - A new method for incorporating weighted temporal and spatial smoothing in the
      inverse problem of electrocardiography.
AB  - In this paper, we present a method for incorporating temporal smoothing (TS) into
      the estimate of epicardial potentials from body surface potential data. Our
      algorithm employs a different spatial smoothing parameter, chosen by the
      composite residual error and smoothing operator criteria, at each time step in
      the sequence. The total spatial smoothing term is then simply partitioned between
      temporal and spatial smoothing. The algorithm appears to be quite robust with
      regard to this partitioning. The new method was evaluated in the setting of
      additive Gaussian noise, but otherwise realistic conditions of body geometry and
      reference epicardial potentials. In examining the match between estimated and
      measured electrograms, or the match between estimated isopotential maps and
      measured isopotential maps, the estimates constructed using the new TS algorithm
      produced consistently smaller relative errors than those constructed using a
      quasi-static (QS) algorithm or those constructed by postprocessing the QS
      estimate with a moving average filter.

PMID- 12214880
TI  - A new real-time retinal tracking system for image-guided laser treatment.
AB  - A new system is proposed for tracking sensitive areas in the retina for computer
      assisted laser treatment of choroidal neovascularization (CNV). The system
      consists of a fundus camera using red-free illumination mode interfaced to a
      computer that allows real-time capturing of video input. The first image acquired
      is used as the reference image and utilized by the treatment physician for
      treatment planning. A grid of seed contours over the whole image is initiated and
      allowed to deform by splitting and/or merging according to preset criteria until
      the whole vessel tree is demarcated. Then, the image is filtered using a one
      dimensional Gaussian filter in two perpendicular directions to extract the core
      areas of such vessels. Faster segmentation can be obtained for subsequent images
      by automatic registration to compensate for eye movement and saccades. An
      efficient registration technique is developed whereby some landmarks are detected
      in the reference frame then tracked in the subsequent frames. Using the relation
      between these two sets of corresponding points, an optimal transformation can be
      obtained. The implementation details of proposed strategy are presented and the
      obtained results indicate that it is suitable for real-time location
      determination and tracking of treatment positions.

PMID- 12214881
TI  - Correlation-based alignment of multichannel signals and application to paroxysmal
      events.
AB  - We propose a new group-theoretical approach to the problem of alignment of time
      events in multichannel signal recordings. Such an alignment is an essential phase
      in the classification of transients in electroencephalogram/magnetoencephalogram
      (MEG) signals. A common reference frame is reconstructed applying a time
      translation transformation based on delayed mutual correlation functions of the
      individual events. The method is applied to MEG data sets recorded from epileptic
      patients showing paroxysmal interictal discharges.

PMID- 12214882
TI  - A large-scale simulation of the piriform cortex by a cell automaton-based network
      model.
AB  - An event-driven framework is used to construct a physiologically motivated large
      scale model of the piriform cortex containing in the order of 10(5) neuron-like
      computing units. This approach is based on a hierarchically defined highly
      abstract neuron model consisting of finite-state machines. It provides
      computational efficiency while incorporating components which have identifiable
      counterparts in the neurophysiological domain. The network model incorporates
      four neuron types, and glutamatergic excitatory and GABA(A) and GABA(B)
      inhibitory synapses. The spatio-temporal patterns of cortical activity and the
      temporal and spectral characteristics of simulated electroencephalograms (EEGs)
      are studied. In line with previous experimental and compartmental work, 1) shock
      stimuli elicit EEG profiles with either isolated peaks or damped oscillations,
      the response type being determined by the intensity of the stimuli, and 2)
      temporally unpatterned input generates EEG oscillations supported by model-wide
      waves of excitation.

PMID- 12214883
TI  - A novel method for the detection of apnea and hypopnea events in respiration
      signals.
AB  - The monitoring of breathing dynamics is an essential diagnostic tool in various
      clinical environments, such as sleep diagnostics, intensive care and neonatal
      monitoring. This paper introduces an innovative signal classification method that
      is capable of on-line detection of the presence or absence of normal breathing.
      Four different artificial neural networks are presented for the recognition of
      three different patterns in the respiration signals (normal breathing, hypopnea,
      and apnea). Two networks process the normalized respiration signals directly,
      while another two use sophisticatedly preprocessed signals. The development of
      the networks was based on training sets from the polysomnographic records of nine
      different patients. The detection performance of the networks was tested and
      compared by using up to 8000 untrained breathing patterns from 16 different
      patients. The networks which classified the preprocessed respiration signals
      produced an average detection performance of over 90%. In the light of the
      moderate computational power used, the presented method is not only viable in
      clinical polysomnographs and respiration monitors, but also in portable devices.

PMID- 12214884
TI  - A successive cancellation algorithm for fetal heart-rate estimation using an
      intrauterine ECG signal.
AB  - In this paper, we present a two-stage successive cancellation (SC) algorithm that
      sequentially separates fetal and maternal heartbeats from an intrauterine
      electrocardiogram (IuECG) signal containing both fetal and maternal QRS
      complexes. The ECG signal is modeled as a series of fetal, maternal, and noise
      events. Peak detection is first employed to locate the potential fetal and
      maternal QRS complexes, referred to as candidate events. Each stage automatically
      generates a template of a source from the candidate events in the initialization
      period, and thereafter performs classification of the remaining candidate events
      based on a template matching technique. The detected events of the stronger
      signal are subtracted from the composite ECG signal prior to initialization and
      classification of the weaker signal. Once the fetal and maternal complexes are
      successfully detected and separated, a counting mechanism is utilized to derive
      the corresponding heart rates. Computer simulation results on real IuECG data
      demonstrate the effectiveness of the SC algorithm.

PMID- 12214885
TI  - Deconvolution estimation of motor unit conduction velocity distribution.
AB  - A conduction velocity distribution (CVD) estimator that incorporates volume
      conductor modeling of the muscle voluntary response is introduced in this paper.
      The CVD estimates are obtained from two correlation functions, an autocorrelation
      and a cross, computed from myoelectric signal recorded at the skin surface. The
      performance of the proposed estimator is evaluated for simulated and experimental
      data. The study includes assessment of the estimator bias and standard deviation,
      as well as its sensitivity to errors in the model parameters. Simulations show
      its good performance in terms of estimator bias. A filtering technique also helps
      reduce its variance. However, the inaccuracy introduced in the estimation of
      model parameters considerably deteriorates the estimator performance.

PMID- 12214886
TI  - Comparison of machine learning and traditional classifiers in glaucoma diagnosis.
AB  - Glaucoma is a progressive optic neuropathy with characteristic structural changes
      in the optic nerve head reflected in the visual field. The visual-field
      sensitivity test is commonly used in a clinical setting to evaluate glaucoma.
      Standard automated perimetry (SAP) is a common computerized visual-field test
      whose output is amenable to machine learning. We compared the performance of a
      number of machine learning algorithms with STATPAC indexes mean deviation,
      pattern standard deviation, and corrected pattern standard deviation. The machine
      learning algorithms studied included multilayer perceptron (MLP), support vector
      machine (SVM), and linear (LDA) and quadratic discriminant analysis (QDA), Parzen
      window, mixture of Gaussian (MOG), and mixture of generalized Gaussian (MGG). MLP
      and SVM are classifiers that work directly on the decision boundary and fall
      under the discriminative paradigm. Generative classifiers, which first model the
      data probability density and then perform classification via Bayes' rule, usually
      give deeper insight into the structure of the data space. We have applied MOG,
      MGG, LDA, QDA, and Parzen window to the classification of glaucoma from SAP.
      Performance of the various classifiers was compared by the areas under their
      receiver operating characteristic curves and by sensitivities (true-positive
      rates) at chosen specificities (true-negative rates). The machine-learning-type
      classifiers showed improved performance over the best indexes from STATPAC.
      Forward-selection and backward-elimination methodology further improved the
      classification rate and also has the potential to reduce testing time by
      diminishing the number of visual-field location measurements.

PMID- 12214887
TI  - Estimation of neural dynamics from MEG/EEG cortical current density maps:
      application to the reconstruction of large-scale cortical synchrony.
AB  - There is a growing interest in elucidating the role of specific patterns of
      neural dynamics--such as transient synchronization between distant cell
      assemblies--in brain functions. Magnetoencephalography
      (MEG)/electroencephalography (EEG) recordings consist in the spatial integration
      of the activity from large and multiple remotely located populations of neurons.
      Massive diffusive effects and poor signal-to-noise ratio (SNR) preclude the
      proper estimation of indices related to cortical dynamics from nonaveraged
      MEG/EEG surface recordings. Source localization from MEG/EEG surface recordings
      with its excellent time resolution could contribute to a better understanding of
      the working brain. We propose a robust and original approach to the MEG/EEG
      distributed inverse problem to better estimate neural dynamics of cortical
      sources. For this, the surrogate data method is introduced in the MEG/EEG inverse
      problem framework. We apply this approach on nonaveraged data with poor SNR using
      the minimum norm estimator and find source localization results weakly sensitive
      to noise. Surrogates allow the reduction of the source space in order to
      reconstruct MEG/EEG data with reduced biases in both source localization and time
      series dynamics. Monte Carlo simulations and results obtained from real MEG data
      indicate it is possible to estimate non invasively an important part of cortical
      source locations and dynamic and, therefore, to reveal brain functional networks.

PMID- 12214888
TI  - Time-frequency spectral estimation of multichannel EEG using the Auto-SLEX
      method.
AB  - In this paper, we apply a new time-frequency spectral estimation method for
      multichannel data to epileptiform electroencephalography (EEG). The method is
      based on the smooth localized complex exponentials (SLEX) functions which are
      time-frequency localized versions of the Fourier functions and, hence, are ideal
      for analyzing nonstationary signals whose spectral properties evolve over time.
      The SLEX functions are simultaneously orthogonal and localized in time and
      frequency because they are obtained by applying a projection operator rather than
      a window or taper. In this paper, we present the Auto-SLEX method which is a
      statistical method that 1) computes the periodogram using the SLEX transform, 2)
      automatically segments the signal into approximately stationary segments using an
      objective criterion that is based on log energy, and 3) automatically selects the
      optimal bandwidth of the spectral smoothing window. The method is applied to the
      intracranial EEG from a patient with temporal lobe epilepsy. This analysis
      reveals a reduction in average duration of stationarity in preseizure epochs of
      data compared to baseline. These changes begin up to hours prior to electrical
      seizure onset in this patient.

PMID- 12214889
TI  - Real-time speckle reduction and coherence enhancement in ultrasound imaging via
      nonlinear anisotropic diffusion.
AB  - This paper presents a novel approach for speckle reduction and coherence
      enhancement of ultrasound images based on nonlinear coherent diffusion (NCD)
      model. The proposed NCD model combines three different models. According to
      speckle extent and image anisotropy, the NCD model changes progressively from
      isotropic diffusion through anisotropic coherent diffusion to, finally, mean
      curvature motion. This structure maximally low-pass filters those parts of the
      image that correspond to fully developed speckle, while substantially preserving
      information associated with resolved-object structures. The proposed
      implementation algorithm utilizes an efficient discretization scheme that allows
      for real-time implementation on commercial systems. The theory and implementation
      of the new technique are presented and verified using phantom and clinical
      ultrasound images. In addition, the results from previous techniques are compared
      with the new method to demonstrate its performance.

PMID- 12214890
TI  - Diurnal variability of peak expiratory flow.
AB  - Diurnal variation in peak expiratory flow (PEFvar) has been suggested as a
      surrogate for bronchial hyperreactivity, and may be a useful tool in the
      management of bronchial asthma. Several indices have been postulated to measure
      PEFvar; however, the number of daily measurements and the timing of recordings
      are not clearly established. Although several investigators have defined ranges
      for PEFvar in healthy individuals, clear cutoff values that differentiate
      asthmatics from others are not available. Despite this shortcoming, PEFvar is an
      important measurement in screening and diagnosis of asthma in population-based
      studies, as well as for assessing disease severity and prognosis. Treatment of
      asthma with either inhaled corticosteroids or bronchodilators may influence the
      magnitude of PEFvar in a complex fashion. Therefore, PEFvar should only be
      interpreted in conjunction with other clinical and laboratory information.

PMID- 12214891
TI  - Comparison of acute bronchodilator effects of inhaled ipratropium bromide and
      salbutamol in bronchial asthma.
AB  - Both salbutamol (sal) and ipratropium (ipra) are effective bronchodilators in
      asthma patients. However, the issue of their relative status remains unresolved
      and the clinical factors affecting the responses have also not been adequately
      defined. The two drugs were compared in 44 asthmatics in a double-blind,
      randomized crossover, placebo-controlled study. There were four test days on
      which each patient received the following sequences of drugs: sal-sal-ipra, sal
      sal-placebo, ipra-ipra-sal, and ipra-ipra-placebo. Baseline forced expiratory
      volume in 1 sec (FEV1) was similar on the four days. The change in FEV1 produced
      by salbutamol when given as the first bronchodilator was 0.50 +/- 0.30 L as
      compared to a change of 0.39 +/- 0.27 L produced by ipratropium (p < 0.01). Both
      salbutamol and ipratropium resulted in statistically similar further improvements
      in FEV1 when given as the second drug. There was, however, a wide patient-to
      patient variability in response, with some patients showing greater improvement
      with salbutamol and others with ipratropium. Younger patients showed a greater
      response to salbutamol as compared to older patients, while no such difference
      was observed with ipratropium. Males responded better to both the drugs as
      compared to females. It was concluded that both salbutamol and ipratropium are
      effective bronchodilators in asthma patients, although the overall response to
      salbutamol appears to be superior. However, some patients may respond better to
      one or other of the two drugs. Sequential administration of the two drugs may be
      a justified therapeutic approach as some patients show have further improvement
      with use of the second drug.

PMID- 12214892
TI  - Risk factors determining allergic airway diseases in Turkish subjects.
AB  - With regard to changes in life-style after the 1980s, the reflection of
      environmental factors on the evolution of allergic airway disease (AAD) has not
      yet been analyzed in Turkey. In this trial, we aimed to determine the factors
      related to AAD in Turkish subjects. Patients diagnosed as having asthma and/or
      rhinitis with positive skin prick tests (SPTs) were accepted as members of the
      "atopic group" (n = 235). Subjects demonstrated to have negative SPTs and no
      clinical evidence of any atopic disorder were accepted as members of the
      "nonatopic control group" (n = 84). Data obtained from a questionnaire applied
      cross-sectionally to the study groups were compared for risk factor analysis.
      According to the results of univariate analysis, nonatopic controls were found to
      have been born in villages more frequently than those in the atopic group (14.3%
      vs. 4.7%, p = 0.02). Atopic group members had lived in apartments during
      childhood more frequently than nonatopic controls (53.6% vs. 38%, p = 0.04). A
      topic group members, particularly the asthmatics, had lower sibship size (< or =
      1 sibling) (41.3% vs. 16.7%, p = 0.0003) and nonatopic subjects had higher
      sibship size (> or = 3 siblings) (73.8% vs. 43.4%, p < 0.0001). The rate of
      maternal atopy was higher in the atopic group (24.7% vs. 9.5%, p = 0.02). Place
      of birth, sibship size, and atopic status of the mother, but not house type, were
      found to be significant in the multivariate analysis. As a conclusion, rural life
      style seems to have a protective effect on the development of atopy in Turkey. On
      the contrary, factors directly or indirectly related to urban life-style during
      early childhood were found to be associated with the allergic airway diseases.

PMID- 12214893
TI  - Safety of chewable tablets for children.
AB  - New emphasis on pediatric drug development makes the availability of safe, easy
      to-use dosage formulations imperative for clinical practice. Chewable tablets are
      a widely used pediatric dosage form; however, a literature review on the safety
      of this formulation has not been published. We have, therefore, determined the
      safety of chewable tablets in the pediatric age group based on the published
      literature. A search of safety information on chewable tablets was performed from
      the published literature dating from January 1966 to January 1999. Search terms
      included tablet, chewable tablet, drug formulation, aspiration, choking,
      asphyxia, airway obstruction, and foreign body. Additional information was
      obtained from the Physician's Desk Reference, by purchasing products at a local
      drug store, from calls to manufacturers, and from the IMS Health National
      Prescription Audit Plus 7. Human, English-language studies of two types were
      included, clinical articles with any mention of chewable tablets, and aspiration
      case series. The results of this review showed that more than 60 chewable tablet
      formulations are approved for use in the United States. Medical issues, including
      foreign-body injuries, related to the chewable-tablet formulation were extremely
      rare. The advantages of chewable tablets include palatability, stability, precise
      dosing, portability, and ease of delivery. It is concluded that the available
      literature suggests that chewable tablets provide a safe, well-tolerated
      alternative to traditional pediatric drug formulations and offer significant
      advantages in children 2 years of age and older.

PMID- 12214894
TI  - A preliminary retrospective treatment and pharmacoeconomic analysis of asthma
      care provided by allergists, immunologists, and primary care physicians in a
      teaching hospital.
AB  - Allergy immunology specialists (AIs) differ from primary care physicians (PCP) in
      their treatment of asthma. A limited retrospective chart review of several visits
      over a 1-year period in 1997 evaluating the quality of asthma care by AIs vs.
      PCPs was conducted in an academic center. Data concerning quality, effectiveness
      and cost of asthma care was randomly collected from 15 AIs and 15 PCPs from
      charts at 3-month intervals over a 1-year period. Information obtained from data
      collection forms revealed that asthma patients evaluated by AIs had more visits
      and received a greater quantity of medication compared to those treated by PCPs.
      All 15 patients with persistent asthma followed by AIs were treated with inhaled
      corticosteroids at each visit in contrast to only 80% of those treated by PCPs.
      The total numbers of controller medications (i.e., inhaled corticosteroids,
      salmeterol, cromolyn, and theophylline) that were utilized, as recommended, by
      the National Asthma Expert Panel (NAEP) of the National Heart, Lung, and Blood
      Institute (NHLBI) guidelines were 70 by AIs vs. 24 by PCPs over three visits.
      Cromolyn was prescribed five times over three visits by AIs and not at all by
      PCPs. Recognition and treatment of coexisting allergic rhinitis was evident in
      only 13% of patients treated by PCPs as compared to 80% in those treated by AIS.
      (p < 0.0001). However, all patients treated by AIs were skin tested to explore
      the presence of allergic triggers, while no patients treated by PCPs were
      evaluated for IgE-mediated reactions. Treatment cost for allergic rhinitis was
      therefore higher, at $2039, for AIs as compared to $741 for PCPs. There were no
      peakflow values in charts obtained from PCPs. However, all charts from AIs had
      peakflow values, which improved during the course of therapy in 33% of patients.
      Total medication costs for asthma were higher for AIs @ $5,646.30 vs. $1,932.25
      for PCPs. Total medication costs for allergic rhinitis plus asthma were higher
      for AIs @ $7615 vs. $2681 for PCPs. However, patients treated by AIs had more
      severe asthma and required more frequent visits. Ipratropium bromide was
      prescribed a total of four times over several visits by PCPs vs. only once by
      AIs. In comparing asthma care between AI specialists and PCPs, it was found that
      AI specialists treat more severe asthmatics, provide more frequent follow-up
      visits, utilize peak flow rates, prescribe more controller medications, and more
      often recognize and treat comorbid conditions such as allergic rhinitis that
      impact on asthma care. Thus, although treatment costs for AIs are higher, these
      costs are justified by a quality of care that is more consistent with national
      (NHLBI) guidelines.

PMID- 12214895
TI  - Schoolboys with bronchial asthma in Al-Khobar City, Saudi Arabia: are they at
      increased risk of school absenteeism?
AB  - The objective of this cross-sectional study was to determine the mean period of
      school absenteeism (MPSA) among asthmatic Saudi schoolboys of Al-Khobar City and
      to determine the factors associated with the absenteeism. The methodology
      included the distribution of a self-administered questionnaire, which was
      completed by the parents of 1482 schoolboys who satisfied the selection criteria
      of the study. The prevalence rate of questionnaire-diagnosed asthma (QDA) was
      9.5% (141/1482). The MPSA among questionnaire-diagnosed asthmatic boys (QDAs) was
      13.6 +/- 3.4 days compared to 3.7 +/- 2.2 days among non questionnaire-diagnosed
      asthmatic boys (non QDAs). Among QDAs, the MPSA was associated significantly and
      positively with those who were younger, and with decreasing levels of
      socioeconomic class, histories of pets at home, presence of a currently smoking
      family member (father or both parents), visit to a hospital emergency room, and
      admission to hospital. It was significantly and negatively associated with
      concomitant use of prophylactic medication(s), including those used
      appropriately. The QDAs from middle and lower socioeconomic classes showed less
      use of prophylactic medication(s) but more histories of visits to an emergency
      room and of admissions to hospital. The multiple linear regression equation for
      the total period of school absenteeism (TPSA) during the 1995 academic year was
      generated. Asthmatic school children have a higher MPSA compared to their non
      asthmatic classmates. The risk of suffering the impacts of this disease is shown
      to be particularly increased among QDAs belonging to less socioeconomically
      advantaged families.

PMID- 12214896
TI  - Development of a drug treatment-based severity measure in childhood asthma.
AB  - Valid measures of severity are crucial in asthma pharmacoepidemiological
      research. This study reports the development and validation of a severity measure
      in childhood asthma for application to health care administrative data. A drug
      treatment-based asthma severity measure was developed following the stepped care
      approach to treatment, and this was applied to a cohort of 16,862 children who
      met a case definition for asthma drug prescription use between January 1995 and
      March 1996. Assessments were made of the measure's reliability, validity, and
      responsiveness to change over time. The drug treatment-based asthma severity
      measure classified 42% of children as having mild asthma, 37% as having moderate
      asthma, 19% as having moderate-severe asthma, and 2% as having severe asthma.
      Agreement on severity classification between two successive time periods was
      excellent (kappa = 0.82). Children classified as having severe asthma were
      significantly more likely than children with mild-moderate asthma to have
      previous asthma hospitalizations, to visit asthma specialists, to have high
      physician utilization, and to require hospital critical care. They were more
      likely to be reclassified as having severe asthma 2 years later. These findings
      show that a drug treatment-based severity measure in childhood asthma, which can
      be applied to prescription data, has good reliability and validity, and is
      responsive to changes in asthma severity over time.

PMID- 12214897
TI  - Self-reported asthma prevalence in adults in California.
AB  - Data from the 1998 California Behavioral Risk Factor Surveillance System (BRFSS)
      were examined. The BRFSS is an ongoing statewide telephone survey of randomly
      selected adults. The prevalence of self-reported lifetime asthma was 13.6% and
      the prevalence of active asthma was 6.6%. Prevalence rates were highest among
      African-Americans and lowest among Hispanics. Associations between asthma and
      gender, obesity, smoking, depression, migraine, and income were also examined.
      Active asthma was associated with low income, smoking, obesity, migraine, and
      depression in women, but not in men. The relationships observed suggest complex
      interactions between asthma and other chronic conditions, gender, and life-style.

PMID- 12214898
TI  - Effect of interleukin-1beta and tumor necrosis factor-alpha on the expression of
      G-proteins in CD4+ T-cells of atopic asthmatic subjects.
AB  - Chronic use of beta2-agonists and increased production of inflammatory mediators
      during the late allergic reaction after the antigen challenge result in the
      desensitization of beta-adrenoceptors in the airways with an accompanying rise in
      non-specific airway hyperresponsiveness. Several proinflammatory cytokines,
      including interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF
      alpha), play a significant role in orchestrating and perpetuating the
      inflammatory response and induce the decreased response to bronchodilators in
      vitro. However, the underlying mechanisms are unknown. In this study, we examined
      the effect of two cytokines, IL-1beta and TNF-alpha, on the expression of guanine
      nucleotide binding regulatory proteins (G-proteins), Gs alpha and Gi alpha-3, by
      Western blotting in the CD4+ cells of nonatopic nonasthmatic (NANA), atopic
      nonasthmatic (ANA), and atopic asthmatic (AA) subjects. In the purified CD4+
      cells, the basal expression of Gs alpha was higher in the ANA group, and
      significantly lower in the AA group as compared to the NANA group. The basal
      expression of Gi alpha-3 was significantly greater (3-15 fold) than Gs alpha,
      with no significant difference between any of the three groups. Both cytokines IL
      1beta and TNF-alpha significantly decreased the expression of Gs alpha in the
      CD4+ cells of the NANA and ANA groups, with no effect in the AA group. However,
      these cytokines increased the expression of Gi alpha-3, proteins in the AA group,
      but had no effect in the CD4+ cells of the NANA and ANA groups. These data
      suggest that a decreased response to beta2-agonists in the late allergic response
      in allergic asthmatic subjects could be due to the release of inflammatory
      cytokines, which induce a decrease in the stimulatory G-proteins and an increase
      in the inhibitory G-proteins.

PMID- 12214899
TI  - Regional differences in hospitalizations for asthma in the United States, 1988
      1996.
AB  - Hospitalization rates for asthma are higher in the Northeast United States than
      in other regions, despite similar regional prevalence rates. Whether these higher
      rates reflect differences in asthma presentation or severity or else general
      differences in hospitalizations is unclear. We examined regional differences in
      asthma hospitalizations for the United States from 1988 through 1996 using data
      from the National Hospital Discharge Survey. We classified asthma
      hospitalizations into those in which asthma was either the primary diagnosis or
      any listed diagnosis. From 1988 through 1996, the rate of hospitalizations for
      asthma as the primary diagnosis, per 10,000 population, increased in the
      Northeast, but declined in other regions. By 1996, these rates were 24.5 in the
      Northeast, 18.4 in the Midwest, 15.8 in the South, and 14.2 in the West. The
      Northeast also had the highest absolute rate and the highest rate of increase for
      asthma as any listed diagnosis during the study period. These higher rates of
      asthma hospitalizations in the Northeast occurred despite a 9.3% decline in the
      age-adjusted rate for all hospitalizations in the region. These results indicate
      a greater rate of hospitalization for asthma in the Northeast than in other
      regions, suggesting that asthma there may be more severe.

PMID- 12214900
TI  - Acute asphyxia caused by Gerhardt's syndrome associated with asthma.
AB  - Vocal cord dysfunction (VCD) has been frequently discussed as confounding the
      diagnosis of asthma, and it is recommended to examine vocal cord function in
      cases of difficult asthma. However, there is also strong evidence that asthma may
      be associated with VCD, sometimes masquerading as exercise-induced asthma.
      Gerhardt's syndrome frequently induces severe acute respiratory distress
      requiring ventilatory support, and this condition might be mistaken for a severe
      acute asthma attack. Here, a case of bilateral paralysis of the vocal cords,
      which was associated with asthma, is described.

PMID- 12214901
TI  - Incidence and clinical correlates of increased serum creatine kinase levels in
      persons with spinal cord injury.
AB  - BACKGROUND: Elevated plasma levels of creatine kinase (CPK) are found in various
      neuromuscular conditions as a result of muscle damage and necrosis. Elevated CPK
      has also been described in elite wheelchair athletes and in able-bodied
      individuals after strenuous exercise. METHODS: The incidence of elevated CPK in
      individuals with spinal cord injury (SCI) has not been well established. We
      reviewed laboratory data from 581 individuals with chronic SCI. RESULTS: Most
      individuals with SCI (73.3%) had CPK values within 95% confidence intervals for
      able-bodied individuals. The highest levels were seen in African Americans (21%
      had CPK values > 95 confidence intervals for able-bodied individuals).
      Significant associations between CPK and the following independent variables were
      identified: impairment group, gender, duration of injury, body mass index, and
      ethnic group. Multiple regression analysis revealed significant correlations
      between CPK and oxygen consumption (beta .37, P < .01) in 32 individuals who
      performed the exercise test. CONCLUSIONS: These findings are important for
      clinicians evaluating symptoms of fatigue and myopathy in individuals with SCI.

PMID- 12214902
TI  - Colonic transit time after spinal cord injury: any clinical significance?
AB  - BACKGROUND: Both bowel dysfunction and increases in colonic transit time (CTT)
      are frequently observed in individuals with spinal cord injury; however, it is
      unknown whether there is an association between chronic intestinal problems and
      changes in CTTs. The current study investigates a possible relationship between
      the main intestinal symptoms of SCI patients and CTT values. METHODS: The
      following clinical variables and symptoms were investigated and collected in 30
      individuals with SCI: total time for bowel care, abdominal pain, abdominal gas,
      success of rectal emptying, fecal incontinence, and decrease in quality of life.
      Total and segmental CTTs (right colon, left colon, and rectosigmoid colon) were
      assessed using radiopaque markers. The effects of the sociodemographic variables
      and the clinical symptoms on the different CTTs (total and segmental) were
      analyzed. RESULTS: The assessed clinical conditions were observed in the
      following percentages of subjects: abdominal gas symptoms (70%), fecal
      incontinence (56%), abdominal pain (63%), total time for bowel care > 1 hour
      (11%), difficult rectal emptying (66%), and decrease in quality of life (36%). We
      also observed an increase in total CTT in 47% of subjects; increases in segmental
      CTT were found in the right colon in 23%, in the left colon (60%), and in the
      rectosigmoid segment (23%). Statistical analyses failed to show a significant
      difference in mean CTT values between the group of symptomatic patients (1 or
      more symptoms) and the group of asymptomatic patients. No significant difference
      could be detected in the incidence of each intestinal symptom between the group
      of participants with normal CTT values and those with abnormal CTT values. For
      each of the clinical data assessed separately, a significantly longer CTT (left
      colon) was associated with the lack of abdominal pain (P < .03) and the presence
      of fecal incontinence (P < .01); successful rectal emptying was associated with
      significantly shorter total (P < .02) and segmental CTTs for the left colon (P <
      .01) and rectosigmoid colon (P < .05). CONCLUSIONS: Besides an association
      between shorter CTT and successful rectal emptying, there was little relationship
      between CTTs and intestinal symptoms in this study of patients with SCI.

PMID- 12214903
TI  - Interface pressure characteristics of alternating air cell mattresses in persons
      with spinal cord injury.
AB  - OBJECTIVES: To examine interface pressure characteristics for two alternating air
      cell mattresses used for pressure ulcer prevention and treatment in a spinal cord
      injury population. DESIGN: Prospective evaluation of Dynamic Flotation System
      (DFS) mattress and the Pegasus Airwave Mattress. Subjects acted as their own
      controls. SETTING: Veterans Affairs Medical Center Spinal Cord Injury Unit.
      PARTICIPANTS: Convenience sample of 15 subjects with spinal cord injuries.
      INTERVENTIONS: Minimum, maximum, and average interface pressures, and interface
      pressure range were measured by use of a force-sensing array system. The sacrum
      was chosen as the area of interest. Recordings lasted 9.5-10 minutes. Analyses
      were performed on 19 subjects in the supine and 45-degree upright positions for
      both mattresses. RESULTS: Maximum and average interface pressures and interface
      pressure ranges were significantly higher, whereas minimum interface pressures
      were significantly lower on the Pegasus vs the DFS. For either mattress, the 45
      degree position resulted in significantly greater interface pressures. There was
      no consistent correlation found between interface pressures and body mass index.
      CONCLUSIONS: Interface pressure characteristics of these two mattresses are very
      different, and neither mattress retains performance in the 45-degree position.
      Which interface pressure characteristic is most clinically relevant remains
      undetermined. Avoidance of the 45-degree sitting position is recommended.

PMID- 12214904
TI  - The effects of colostomy on the quality of life in patients with spinal cord
      injury: a retrospective analysis.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of colostomy on
      the quality of life (QOL) in patients with spinal cord injury (SCI) by designing
      a questionnaire that used self-reported data and correlating these data with the
      clinical information obtained from patients' medical records. MATERIALS AND
      METHODS: A comprehensive QOL questionnaire was designed to specifically address
      the following 5 domains: physical health, psychosocial adjustment, body image,
      self-efficacy, and recreation/leisure. This questionnaire was completed during a
      telephone or an in-person interview. The subjective data derived from the
      questionnaire were correlated with objective medical information obtained from a
      review of medical records. RESULTS: The QOL improved significantly (t = 9.1 28, P
      < .0001) after colostomy. All 27 (100%) patients were "satisfied," and 16 (59%)
      of them were "very satisfied" with colostomy. Nineteen (70%) patients would have
      preferred to have the colostomy done earlier, and only 3 (11%) patients wished it
      reversed. Colostomy reduced the number of hospitalizations caused by chronic
      bowel dysfunction by 70.4%. After colostomy, the average amount of time spent on
      bowel care was reduced from 117.0 min/day to 12.8 min/day (t = 7.964, P < .0001).
      All patients stated that colostomy simplified bowel care routine and increased
      independence. Significant improvements were recorded in the areas of physical
      health, psychosocial adjustment, and self-efficacy. Stoma prolapse and wound
      dehiscence were the most common complications of stomal surgery. When compared
      with medical data, patients were able to reliably recall average time with bowel
      problems (r = .881, P < .0001) and stomal surgery complications (r = .810, P <
      .0001). CONCLUSION: Colostomy is a safe and effective treatment for chronic bowel
      dysfunction in patients with spinal cord injury. It is well accepted by the
      patients and significantly improves QOL and bowel management procedures.
      Correlation analysis indicates that subjective patient-reported data are
      consistent with objective data obtained from the medical records.

PMID- 12214905
TI  - Life satisfaction in adults with pediatric-onset spinal cord injuries.
AB  - OBJECTIVE: To determine the level of life satisfaction of adults with pediatric
      onset spinal cord injuries (SCI) and the factors associated with life
      satisfaction. METHOD: A structured interview including standardized measures.
      PARTICIPANTS: Participants were individuals who sustained SCI at age 18 years or
      younger, were 24 years of age or olderat interview, did not have significant
      brain injury, and were living in the United States or Canada. OUTCOME MEASURES: A
      structured interview, the Functional Independence Measure (FIM), the Craig
      Handicap Assessment and Reporting Technique (CHART), the Short-Form 12 (SF-12),
      and the Satisfaction with Life Scale (SWLS). RESULTS: Two hundred sixteen
      individuals were interviewed. Mean age at injury was 1 4 years, mean age at
      interview was 29 years, and mean duration of injury was 14 years. The mean SWLS
      score was 23.6, and the median score was 25. There was not a significant
      difference between men and women, but those with tetraplegia were significantly
      less satisfied than were those with paraplegia. A regression model identified age
      at injury, community mobility (CHART), marital status, use of street drugs,
      perceived mental health (SF-12), and medical complications as predictors of life
      satisfaction. Other factors strongly associated with SWLS were employment,
      income, independent living, FIM total plus physical and sociocognitive domain
      scores, perceived physical health (SF-12), and CHART total plus the subscales of
      physical independence, cognitive independence, and occupation. CONCLUSIONS: Life
      satisfaction in adults with pediatric-onset SCI is associated with demographic,
      injury-related, and functional limitation factors, as well as with health status
      and community integration outcomes.

PMID- 12214906
TI  - Marjolin's ulcer in patients with spinal cord injury.
AB  - BACKGROUND: The term "Marjolin's ulcer" is now synonymous with malignant
      transformation, usually ectodermal and rarely mesenchymal, of chronic ulcers,
      sinus tracts, and burn scars. DESIGN: Literature search and personal experience
      with 5 patients during a 30-year period in a spinal cord injury center. FINDINGS:
      Five cases of Marjolin's ulcer diagnosed among approximately 10,000 patients
      indicate the rarity of the metaplasia. All cases were fatal. CONCLUSIONS: Chronic
      pressure ulcers of more than 10 years' duration should be biopsied to rule out
      malignancy, especially with any change in the nature of the ulcer (eg, exuberant
      granulation and/or bleeding).

PMID- 12214908
TI  - The transition of adolescent males to first sexual intercourse: anticipated or
      delayed?
AB  - CONTEXT: Recognition of the different social, psychological and behavioral
      contexts within which adolescents initiate sexual activity broadens the
      understanding of teenage sexual behavior beyond the typical dichotomy of sexual
      experience vs. inexperience. METHODS: Data from the National Survey of Adolescent
      Males (1988 and 1990-1991) were used in logistic regression analyses to examine
      the influence of background factors on the transition to first intercourse among
      265 teenagers who were not expecting to initiate sex in the next year (delayers)
      and 187 teenagers expecting to do so (anticipators). RESULTS: The most common
      reason for sexual inexperience among delayers was a desire to wait until marriage
      (32%); among anticipators, it was a lack of opportunity to initiate intercourse
      (35%). Anticipators were significantly more likely than delayers to have first
      intercourse within one year of the survey (53% vs. 13%). They also were more
      likely to report risky behaviors, precoital activities and approval of premarital
      sex; risky behavior predicted their onset of first sex (odds ratio, 1.5).
      Delayers were more likely to attend, church and have strict parents and a college
      educated mother. Having a mother with at least some college education increased
      the odds of transition to first intercourse for anticipators (5.2) but decreased
      the odds for delayers (0.2). Having a mother who gave birth as a teenager
      significantly increased the odds for anticipators (14.5). CONCLUSIONS:
      Anticipators' sexual behavior occurs in a high-risk context, whereas delayers may
      have internalized the decision to delay first intercourse and have background
      factors that encourage the delay.

PMID- 12214907
TI  - Is lack of sexual assertiveness among adolescent and young adult women a cause
      for concern?
AB  - CONTEXT: Understanding young women's sexual assertiveness is critical to
      developing effective interventions to promote sexual health and reduce sexual
      risk-taking and violence. Young women's perception of their sexual rights may
      vary according to demographic characteristics, sexual health behaviors and
      victimization history. METHODS: Data were collected from 904 sexually active 14
      26-year-old clients of two family planning clinics in Texas, reflecting their
      perceptions of their right to communicate expectations about or control aspects
      of their sexual encounters. Logistic regression analysis was used to assess which
      characteristics were independently associated with believing that one never has
      each specified sexual right. RESULTS: Almost 2096 of women believed that they
      never have the right to make their own decisions about contraception, regardless
      of their partner's wishes; to tell their partner that they do not want to have
      intercourse without birth control, that they want to make love differently or
      that their partner is being too rough; and to stop foreplay at any time,
      including at the point of intercourse. Poor grades in school, sexual
      inexperience, inconsistent contraceptive use and minority ethnicity were
      independently associated with lacking sexual assertiveness. CONCLUSIONS: Many
      sexually active young women perceive that they do not have the right to
      communicate about or control aspects of their sexual behavior. Interventions to
      prevent sexually transmitted diseases, unwanted pregnancy and coercive sexual
      behaviors should include strategies to evaluate and address these perceptions.

PMID- 12214909
TI  - Factors affecting British teenagers' contraceptive use at first intercourse: the
      importance of partner communication.
AB  - CONTEXT: Despite the growing body of knowledge about teenager's sexual and
      contraceptive behavior in the United Kingdom, much quantitative work has failed
      to consider the broader social contexts in which this behavior occurs. METHODS: A
      1999 survey of 963 full-time students aged 16-18 gathered information on
      individual, contextual and background factors. Logistic regression analyses were
      conducted to investigate how these factors determine use of a modern method at
      first sex and whether such use is discussed beforehand. RESULTS: Three factors
      were significantly associated with the odds of contraceptive use at first sex
      among young men-discussing contraception beforehand (odds ratios, 5.7-13.8),
      giving an intimate reason for having sex the first time (6.4) and having parents
      who portrayed sexuality positively during childhood and the early teenage years
      (1.2). For young women, five factors significantly predicted use-communication
      (odds ratios, 6.2-15.0), age at first sex (1.8), not having visited a service
      provider (5.0), feeling comfortable interacting with teenage males (1.2) and
      "sort of" or not expecting to have sex (0.2 and 0.4, respectively). Among young
      men, the factors significantly associated with the odds of having discussed
      contraception were the level of social deprivation, the length of the
      relationship and parents' openness to talking about sex; among young women, the
      factors were the number of intimate reasons given for having sex and the warmth
      and availability of parents. CONCLUSIONS: Efforts to increase young people's
      ability to negotiate sexual and contraceptive decision-making should be
      multifaceted. It is essential that parents provide a supportive climate
      throughout childhood and adolescence, where discussions of sexual issues are
      acceptable and where families feel comfortable talking openly.

PMID- 12214910
TI  - Consequences for infants of parental disagreement in pregnancy intention.
AB  - CONTEXT: Despite the well-established literature on couples' pregnancy intentions
      and on the consequences of unintended pregnancy, the effects of parents'
      disagreement in fertility intentions has not been explored. Parental disagreement
      in pregnancy intention, as well as a father's pregnancy intention, may affect
      infant health. METHODS: Logistic regression analyses using 1979-1992 data from
      the National Longitudinal Survey of Youth assess effects of unintendedness and
      parents' disagreement on outcomes related to infants' health and development.
      Analyses are conducted separately for married and unmarried women; for women of
      each marital status, one set of analyses includes extensive controls for
      socioeconomic background, and a second compares effects of intended and
      unintended pregnancies within the same family. RESULTS: Infants whose conception
      was intended by their mother but not their father are at elevated risk of adverse
      health events. When a pregnancy was not intended by the mother, risks are higher
      than they are if both parents intended the pregnancy, but they differ little
      according to father's intention. Thus, it may be useful to classify pregnancies
      as intended by both parents or not intended by at least one. In comparisons of
      siblings, unintended fertility (so defined) is associated with delayed prenatal
      care and reduced initiation of breastfeeding. CONCLUSION: Information on both
      parents' fertility intentions is needed to identify infants at risk of adverse
      health and developmental outcomes.

PMID- 12214911
TI  - The extent of pregnancy mistiming and its association with maternal
      characteristics and behaviors and pregnancy outcomes.
AB  - CONTEXT: The National Survey of Family Growth (NSFG) classifies pregnancies as
      intended, mistimed or unwanted. However, these categories could be too broad, as
      a woman's feelings about a pregnancy, her health behaviors during pregnancy and
      thus her pregnancy outcomes may vary according to whether her pregnancy is
      moderately or seriously mistimed. These relationships have not yet been explored.
      METHODS: Data from the 1995 NSFG were examined to assess associations between
      pregnancy mistiming and maternal characteristics. Descriptive and multivariate
      analyses were conducted of the extent of mistiming for each maternal
      characteristic. Chi-square and F-tests were used to examine the associations
      between a pregnancy's intendedness--according to a four-category classification-
      and maternal characteristics, maternal happiness ratings, maternal behaviors and
      pregnancy outcomes. RESULTS: Fifty-five percent of mistimed pregnancies were
      mistimed by 24 months or less, 32% were mistimed by 25-60 months and 13% were
      mistimed by more than 60 months. According to multivariate analyses, pregnancies
      among younger women, never-married women and black women were mistimed by
      significantly more months than those among other women. The distribution of
      moderately mistimed pregnancies differed significantly from those of both
      seriously mistimed and unwanted pregnancies according to most maternal
      characteristics; there were few differences between intended and moderately
      mistimed pregnancies, and between seriously mistimed and unwanted pregnancies.
      CONCLUSIONS: Mistiming is not a unitary construct. Its extent is associated with
      maternal characteristics and behaviors. Future research on pregnancy intention
      should examine the extent of mistiming and consider alternatives to traditional
      definitions of intendedness.

PMID- 12214912
TI  - Sexual assertiveness and adolescents' sexual rights.

PMID- 12214913
TI  - Delayed Salmonella bacteriuria in a patient infected with Schistosoma
      haematobium.
AB  - The authors report a case of Schistosoma haematobium infection with delayed
      occurrence of Salmonella bacteriuria following treatment of schistosomiasis.
      Standard models of interaction between these two pathogens may not be fully
      satisfactory in such a case of co-infection. The role played by a decreased host
      immune response following schistosomiasis may thus be highlighted to explain a
      delayed or prolonged infection with Salmonella.

PMID- 12214914
TI  - Effect of Echinostoma liei infection on alterations of protein content and some
      enzymes in Biomphalaria alexandrina snails.
AB  - The survival rate and fecundity of B. alexandrina were greatly reduced when
      exposed to E. liei miracidia. Also, exposure of B. alexandrina snails to E. liei
      miracidia induced a disruption in the snail metabolism and this effect was more
      pronounced in 20-days post-miracidial exposure group than in 10-days group.
      Protein content was significantly reduced in all exposed snail groups than in the
      control group. A significant elevation in the levels of aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) enzymes was recorded
      also in exposed snails than unexposed ones (control snails). The results
      indicated also that there were significant increases in the levels of acid and
      alkaline phosphatases enzymes in exposed snails.

PMID- 12214915
TI  - Serum IgM. Does it relate to the level of chronicity in fascioliasis?
AB  - Serum IgM and IgG specific to human fascioliasis were reported to monitor
      prepatent and patent human infection respectively. Recently an assay measuring
      the antigen binding avidity of IgG antibodies was proved to be of value in
      identification of the stage of fascioliasis. The present study investigates the
      level of serum IgM in relation to avidity IgG, among acute and chronic Fasciola
      patients (using ELISA). Specific IgM antibody was detected in all acute and in
      88% of chronic cases. IgM serum level was significantly higher in acute cases.
      IgG antibody was found in both acute and chronic cases but with no significant
      difference between the two groups. Regarding IgG avidity, it was found that acute
      cases had low IgG avidity index whereas chronic cases had significantly higher
      avidity. Four chronic patients had high IgM level and high IgG avidity. The egg
      counts as well were relatively high. The possibility of reinfection was
      considered in those cases.

PMID- 12214916
TI  - Comparative study on ELISA, IFA and direct methods in diagnosis of giardiasis.
AB  - A total of 200 cases aged 1-13 years complaining of symptoms suggestive of
      giardiasis in addition to thirty normal healthy children as a control group was
      examined clinically and laboratory using stool examination and detection of
      Giardia coproantigen in faeces by Dot ELISA and direct IFA. Stool examination
      detected 39 cases (19.5%) while Dot ELISA and direct IFA detected 49 cases
      (24.5%) with 100% sensitivity and 93.8% specificity. The common clinical findings
      were diarrhea, abdominal cramps, anorexia, underweight, pallor and manifestations
      of vitamin deficiency. The results were discussed.

PMID- 12214918
TI  - Seasonal distribution of fleas infesting rodents in various Egyptian eco
      geographical areas and their susceptibility to malathion.
AB  - The rodent population and their ectoparasites especially fleas, in various
      Egyptian eco-geographical areas were studied It was noticed that flea infestation
      varied according to rodent species and to the bioclimatic conditions. High flea
      indices were recorded in certain seasons of the year. The flea index was above
      one during spring in the southern of Nile Delta and semi-arid coastal areas, in
      summer in northern coastal areas and in autumn in southern of Nile Delta.
      Susceptibility tests were conducted using the WHO diagnostic dose of malathion
      (5%) on three populations of fleas collected from Qualyobia, Suez and Beni-Suef
      Governorates. The results indicated that malathion (5%) was very effective on
      fleas collected from Beni-Suef and Suez, but there was an evidence of increased
      tolerance among flea population collected from Qualyobia Governorate.

PMID- 12214917
TI  - Mice immunzation using crude Trichinella spiralis antigen.
AB  - Four hundred laboratory bred male Swiss strain albino mice, seven to ten weeks
      old, were experimentally used to determine the effective mode of immunization
      against T. spiralis infection. In this regard, active immunization using repeated
      injection of T. spiralis muscle larval antigen was used in comparison with three,
      commonly used immunosuppressive drugs (Kenacort, Endoxan and Cyclosporin). Also,
      the minimal oral dose of T. spiralis larvae that can cause the infection was
      estimated. The use of T. spiralis muscle larval antigen was found promising for
      vaccination against the spiralis infection. Although Cyclosporin has an
      immunosuppressive effect, yet it has a direct lethal effect on both adult and
      larvae of T. spiralis, and being recommended for treatment of trichinosis. The
      minimal oral dose of T. spiralis larvae that lead to formation of adult worms in
      the intestine and larvae in muscles was 20 larvae/mouse. Meanwhile, neither
      adults nor larvae were formed below this dose.

PMID- 12214919
TI  - Comparative study on the effect of two Bacillus thuringiensis strains of the same
      serotype on three coleopteran pests of stored wheat.
AB  - The biological control of insect populations of stored products by insect
      pathogens such as, Bacillus thuringiensis (Berliner) is considered as an
      alternative to synthetic insecticides. So far, only B. thuringiensis among
      microbial pesticides have been approved for application against stored product
      insect pests. In this study we used a laboratory culture from an indigenous
      isolate of B. thuringiensis subsp. morrisoni, and the commercial formulation, B.
      thuringiensis subsp. tenebrionis. The bioassays with adults of the three beetle
      species (Rhyzopertha dominica (F.), Silophilus granarius (L.), and Tribolium
      confusum (Jacqueline du Val) and larvae of T. confusum were done at four
      different concentrations 3000, 1000, 500, and 250 ppm. Mortality records were
      made after 7, 14, 21, 28 days of exposure. Among the strains tested, the
      indigenous isolate B. thuringiensis subsp. morrisoni gave the highest mortality
      for adults of R. dominica and T. confusum after 21 and 28 days of exposure. It
      was (67, 78%) and (43, 65%), respectively. Larvae of T. confusum showed that the
      isolate, morrisoni was the most active where it gave mortality records of 76, 60,
      55 and 35% at 3000, 1000, 500 and 250 ppm after 28 days of exposure, while the
      other strain did not show any actual mortality. This demonstrates the possibility
      of using B. thuringiensis subsp. Morrisoni for the protection of stored grains
      from pest infestation.

PMID- 12214920
TI  - A patient with intestinal amoebiasis and cutaneous amoebic ulcer.
AB  - This paper reports a patient with intestinal amoebiasis in concomitant with
      amoebic ulcer in the thigh. The ulcer was suspected to be carcinoma, complicated
      cutaneous leishmaniasis or due to free-living amoebae. The diagnosis was
      confirmed by the pathological and parasitological demonstration of haematophagous
      trophozoites of E. histolytica. The patient was successfully treated with
      Metronidazole.

PMID- 12214921
TI  - Detection of Toxoplasma gondii antigens in urine by reverse latex agglutination
      test during human toxoplasmosis.
AB  - T. gondii antigens were detected in concentrated urine samples of 39 out of 40
      patients with acute toxoplasmosis and in 38 serum samples of the same patients by
      the reverse latex agglutination (RLA) test which showed a high sensitivity of
      97.5% and 95%, respectively. By capture enzyme-linked immunosorbent assay
      (ELISA). T. gondii antigens were detected in concentrated urine samples of 30 out
      of the 40 patients in 29 sera of the same patients, recording a moderate
      sensitivity of 75% and 72.5%, respectively. T. gondii antigens were not detected
      in urine or serum samples of patients with chronic toxoplasmosis by neither RLA
      test nor ELISA. No false positive reaction was observed with urine or serum
      samples of normal--or other parasitic infection--control individuals, recording a
      specificity of 100% for each of RLA test and ELISA. Urine samples were collected
      easily and readily without causing any inconvenience to the individuals enrolled
      in the study. The RLA test was easy to perform and visually interpreted within 2
      3 minutes. The diagnosis of acute toxoplasmosis through the detection of easily
      obtainable urinary T. gondii antigens by the highly sensitive and specific RLA
      test is discussed.

PMID- 12214922
TI  - Morphological and ecological studies on Lymnaea natalensis the snail vector of
      Fasciola gigantica in Egypt.
AB  - Lymnaea natalensis were collected from several localities in Giza Governorate (El
      Mansouria, Kafr Hakim and The Nile). The collected snails were examined for
      cercarial shedding and measurement of shell was carried out using a virner
      caliper. A total of 217 Lymnaea was collected from all habitats and 24 snails
      were found to shed Fasciola gigantica cercariae with infection rate 11.1%. The
      ratio of shell height to shell width (H/W) ranged 1.7-2.1. The ratio between
      length of aperture to shell height (A/H) was almost constant ranged 0.7-0.8.
      While the ratio between length of aperture and shell width (A/W) ranged from to
      1.8. There was a significant positive correlation between shell height and both
      shell width and length of aperture (p<0.001). The same relation was clearly
      indicated between shell width and length of aperture. Also, when the aperture
      length increased the ratio between height and width increased (p<0.05). While,
      the following ratios (H/W), (A/H) and (A/W) remained somewhat constant
      irrespective to the number of whorls. There was a positive correlation between
      number of whorls and each of aperture length, shell length and shell height. On
      maintaining L. natalensis in different pH values, the results showed that at pH 3
      and pH 11, all snails maintained at these pH values died after one day of
      maintenance. While snails survived and laid eggs in the range of pH 5-9.

PMID- 12214923
TI  - Cardiopulmonary pathology in primary murine toxocariasis.
AB  - The cellular infiltration in the 1st week was marked in group III & II compared
      to group I. Parts of larvae were encountered more in the group III than in group
      I & II. Eosinophilic alveolar exudate was detected more in group III in subgroups
      a, b and c, in group II only in subgroup (a) and not in group I. Lobar pneumonia
      was reported in subgroups a and b, in group III in subgroup a, in group II and
      not in group I. Cardiomegaly was reported in 7.1%, 10.7% and 64.2% in group I, II
      and III respectively. Mechanical traumatic effect of larval migration in group
      III was more than group II, I. The extensive haemorrhagic areas and diffuse
      cellular in filtrations and parts of larvae were predominant in subgroup (a) of
      group III in Granulomata & began to appear in subgroup (c). First, it was diffuse
      then became circumscribed in pleural and subpleural areas. Haemorrhagic areas in
      the endocardium was observed in 7.1%, 17.8% and 89.3% in groups I, II and III
      respectively. Foci of cellular infiltration, diffuse interstitial infiltration,
      granulomas, thickening of blood vessels, necrosis of cardiac muscle and focal
      fragmentation of muscle fibers were encountered.

PMID- 12214924
TI  - Scanning electron microscopy of Trichuris trichura.
AB  - Scanning electron microscopy (SEM) studies have been carried out on adult and ova
      of T. trichura to provide the additional topographical details which are not
      obtainable by the light microscopy. The egg of T. trichura has a chitinous shell
      which consists of layers of dense lamellae and bordered by a limiting membrane.
      An operculum and a collar made of chitin form the opercular area. The lamallae of
      the egg shell are diffuse with numerous micropores. Cuticular pores are found
      scattering on the surface of the adult T. trichuira. The spicule sheath in male
      is cylindrical and covered with spines of different shape, size and distribution
      along its length. Spines are compact proximally, reduced in number on the middle
      part and lacking distally. SEM of the cloacal part showed paracloacal papillae.

PMID- 12214925
TI  - Comparative study between elisa IgG, IgM and PCR in diagnosing and studying
      toxoplasmosis in Qualyobia Governorate, Egypt.
AB  - ELISA IgG, IgM antibodies and PCR for toxoplasmosis were performed on 55 women
      with complicated gestation and their babies. Besides, ELISA IgG and IgM were
      applied on 27 uncomplicated gestation (mothers & babies) and 152 randomly
      selected individuals. Seropositivity to specific IgG antibodies was 36.4%, 59.2%
      and 57.9% and for IgM was 27.3%, 7.4% and 10.5% in complicated gestation.
      uncomplicated gestation and random population respectively. PCR was positive in
      20%, 50% and 60% of mothers with abortion, premature deliveries and deliveries of
      babies with congenital anomalies respectively. 55.5% and 40% were found
      seropositive for IgG from normal full term babies and abnormal babies. 13% of
      abnormal babies were IgM positive and 46.6% were PCR positive from the same
      group.

PMID- 12214926
TI  - Scanning electron microscope observations of the surface features of the digenean
      Astiotrema impletum (Looss, 1899) Looss 1900.
AB  - The surface topography of Astiotrema impletum (Looss, 1899) Looss, 1900, from the
      white tilapia Oreochromis niloticus showed regional variations in the
      distribution of spines allover the body. The spines are abundant on the tegument
      of the head region, and the outer border of the ventral sucker. No spines were
      observed on the genital pore, on the inner rim of both the oral and ventral
      suckers, and on the tegumental surface of the posterior extremity of the body
      where the excretory pore is located. The sensory papillae are dome-shaped and
      arranged in a bilateral symmetrical pattern on both the oral and ventral suckers.
      They are also concentrated on the posterior extremity of the body. Some of these
      papillae possess a short knob-like process, while others have no process. Gland
      duct-like apertures were observed in four regions of the body: on the tegument
      covering the anterior extremity of the oral sucker, on the inner rim of the
      ventral sucker, in the region close to the genital aperture and in the region
      lying anterior to the excretory pore. The possible functions of the spines,
      sensory papillae, and gland duct-like apertures were discussed.

PMID- 12214927
TI  - Treatment of experimental heterophyiasis with two plant extracts, areca nut and
      pumpkin seed.
AB  - The effect of water extracts of areca nut and pumpkin seeds in the treatment of
      puppies experimental infected with heterophyiasis gave promising results. Puppies
      were infected through feeding on the muscles of Mugil sp. fish containing the
      encysted metacercariae of H. heterophyes. Decoctions of pumpkin seeds and areca
      nut were administered orally 2 weeks after the start of infection as indicated by
      positive stool examinations. The effect was evaluated by stool examination for
      eggs, and by autopsy for worms in the intestines. A combined extracts of areca
      nut and pumpkin seeds gave an excellent result than when given either extract
      alone.

PMID- 12214928
TI  - Neutrophil apoptosis in acute and chronic Schistosoma mansoni infection.
AB  - Twenty eight patients with acute schistosomiasis mansoni and 32 patients with
      hepatosplenic schistosomiasis were enrolled in this study as well as 20 healthy
      subjects as controls. Measurements of erythrocyte sedimentation rate, complement
      3 (C3), culture of neutrophils and assessment of neutrophil apoptosis were done
      to all patients and control subjects. The results showed that in patients with
      acute schistosomiasis mansoni higher percentage of neutrophil apoptosis was
      found, compared to patients with chronic illness or the control subjects.
      However, patients with chronic schistosomiasis mansoni had the lowest C3 levels
      as well as the lowest leucocytic count.

PMID- 12214929
TI  - Assessing the morbidity of schistosomiasis by measuring eosinophil cationic
      protein in serum.
AB  - Eosinophil cationic protein (ECP) was recently used for assessment of Schistosoma
      haematobium morbidity. In this study, the level of (ECP) in sera of
      schistosomiasis patients was significantly higher than control group, and this
      significance was higher in S. haematobium than S. mansoni groups. No association
      between level of (ECP) in serum and egg count in S. mansoni and S. haematobium
      patients was found. Comparing the correlation of ECP level in serum with
      Schistosoma antigen in both serum and urine, in S. mansoni there was a positive
      association between (ECP) in serum and serum schistosomal antigen but not with
      schistosomal antigen level in urine among S. mansoni infected patients. On the
      other hand, in-patients with S. haematobium infection there is strong association
      between (ECP) level in serum and the level of antigen in urine, but not with
      schistosomal serum antigen level. These results suggest that serum (ECP) may be
      useful and more sensitive and accurate marker of morbidity in S. haematobium
      infection than indirect measures.

PMID- 12214930
TI  - Correlation of plasma levels of tumor necrosis factor, interleukin-6 and nitric
      oxide with the severity of human malaria.
AB  - Thirty two patients of malaria (15, 11 & 6) having P. vivax, uncomplicated and
      complicated P. falciparum malaria respectively, and 10 healthy controls were
      subjected to full clinical and laboratory examinations as well as estimation of
      plasma levels of tumor necrosis factor (TNF), interleukin-6 (IL-6) and nitric
      oxide (NO). The main clinical presentations were fever, pallor, jaundice,
      splenomegaly and anaemia which were more pronounced in patients with complicated
      falciparum malaria. Light coma (50%), convulsions (33.3%), severe anaemia
      (66.6%). severe hypoglycemia (66.6%) and increased blood lactate levels (50%)
      were detected in patients with complicated falciparum malaria. The results showed
      significant elevation of plasma levels of TNF, IL-6 and NO in all malaria
      patients as compared to the controls. The levels were significantly higher in
      patients with complicated falciparum malaria than in the other patient groups.
      The TNF, IL-6 and NO had an effective role in pathogenesis of malaria and their
      levels in can be a useful diagnostic markers for malaria and severity.

PMID- 12214931
TI  - Endoscopic sclerotherapy of oesophageal varices due to hepatosplenic
      schistosomiasis. A randomized controlled trial evaluating effect of sclerosant
      concentration.
AB  - Forty consecutive patients with bleeding oesophageal varices underwent
      paravariceal injection with 2.5% or 5% ethanolamine oleate in a single-blind
      randomized controlled trial. Patients were injected on a weekly basis until
      varices were eradicated and then followed-up for a period of two years. Patients
      injected with 2.5% ethanolamine oleate experienced a significantly shorter
      duration of dysphagia and significantly less episodes of fever, ulceration, and
      luminal narrowing. Patients injected with 5% ethanolamine oleate required
      significantly less injection sessions to eradicate their varices. However, the
      probability of rebleeding was significantly lower in patients injected with 2.5%
      ethanolamine oleate. This study supports the use of ethanolamine in a
      concentration of 2.5% when injected paravariceally as it is associated with less
      complications and a lower probability of rebleeding.

PMID- 12214932
TI  - Parasitological and immunological changes in murine hepatic schistosomiasis
      before and after praziquantel treatment.
AB  - Hepatic fibrosis was assessed by estimating hydroxyproline content in liver
      tissues at the course of the disease and after PZQ treatment. Parasitological
      investigations included egg count in faeces and tissues (liver and intestine) and
      oogram pattern. The results showed that treatment of infected mice with PZQ,
      modulated the course of schistosomiasis as evaluated by highly significant
      decline in hepatic hydroxyproline content as well as egg count in stool and
      tissues. In addition, the oogram pattern showed that PZQ had a lethal effect on
      mature eggs in tissues. PZQ treatment of S. mansoni infected mice, is effective
      in reducing the severity of the disease and in attenuating hepatic fibrosis,
      particularly when the treatment starts early with a suitable dose.

PMID- 12214933
TI  - The potential reservoir role of donkeys and horses in zoonotic fascioliasis in
      Gharbia Governorate, Egypt.
AB  - No doubt, fascioliasis tops all the zoonotic helminthes worldwide. In Egypt,
      human fascioliasis is increasing. The incidence and prevalence of fascioliasis in
      the Egyptian farm animals are well documented. However, none in Egypt has focused
      on the potential role of other domestic farm animals. A preliminary coprologic
      examination of donkeys and horses was done in eight centers of Gharbia
      governorate. The overall rate of infection in donkeys was 3.03%, in horses was
      1.5%, and in mules 0.0%. Horses 2/74 (2.70%) and 1/26 (3.86%) were infected in
      Zefta and El Mahala El Kobra centers respectively. None of the horses was
      infected in other six centers. On the other hand, donkeys showed infection rates
      of 4.6%, 7.6% and 9.09% in the centers of Santa, Zefta and El Mahala El Kobra
      respectively. So, fascioliasis infected donkeys and horses were in Zefta and El
      Mahala El Kobra respectively. The latter center was the relatively highly
      infected one, followed by Zefta and lastly Santa (donkeys only). According to the
      population density of donkeys and horses in Gharbia governorate, donkeys
      represent the 41h rank in number. So, donkeys and to a very less extend, horses
      should be considered within the preventive and control measures of zoonotic
      fascioliasis.

PMID- 12214934
TI  - Dot ELISA for measuring anti-Fasciola IgG isotypes among patients with
      fascioliasis.
AB  - Stool examination using modified Kato thick smear method was performed to detect
      Fasciola eggs and other parasites. Forty-five patients were proved to have
      Fasciola infection by passing eggs in their stool samples. Pallor was the major
      presenting symptom (95.5%) followed by abdominal pain (93.3%) and fever (15.5%).
      Hepatomegaly was recorded in 86.6% of patients compared to 33.3% with
      splenomegaly. Abdominal, ultrasonography revealed hepatomegaly in 38 cases
      (84.4%) and common bile duct dilatation in 35 patients (77.7%). Moreover, 4 cases
      showed Olympic game rings which are diagnostic. All of patients had positive IgG4
      levels, 40 cases were found positives for specific total IgG and 42 cases for
      IgG1, whereas, only 30 cases had positive IgG2 levels (66.6%). Dot-ELISA showed
      that IgG2 and IgG4 giving the highest specificity (>99%), followed by IgG1 (90%)
      and the least specific test was obtained with detection of IgG (85%). From the
      present work, it was concluded that detection of anti-Fasciola isotypes
      especially IgG4 is very specific for accurate diagnosis of fascioliasis.

PMID- 12214935
TI  - Incidence of Parastrongylus cantonensis larvae in different fresh water snails in
      Dakahlia Governorate.
AB  - Samples of snails were collected from different water bodies in Dakahlia
      governorate to assess a survey on the naturally infected snails and their
      infection rate with the Parastrongylus cantonensis larvae. The nematode P.
      cantonensis is associated in the etiology of eosinophilic meningeoencephalitis of
      man. Lanistes carinatus showed the highest rate of infection with 19-400 larvae
      per snail. Biomphalaria alexandrina, B. glabrata, Bulinus truncatus, Lymnaea
      cailliaudi (natalensis), L. alexandrina, and Cleopatra cyclostomoides were found
      naturally infected with the larvae of P. cantonensis for the first time in Egypt.
      The number of larvae per infected snail varied depending on the snail type. The
      highest rate (39.2%) of infected snails was collected from the end canals at
      Tanneekh and the lowest in the river Nile (12.5%).

PMID- 12214936
TI  - Resistance to praziquantel, effect of drug pressure and stability test.
AB  - Various isolates of S. mansoni, originally showed marked diminished
      susceptibility to PZQ, were used in this work. These isolates were taken from
      patients not cured after two or three doses of the drug. They were passed in
      experimental mice and treated with sub-curative doses of PZQ to determine the
      effect of drug pressure on the offspring of these isolates. Upon treatment of the
      second generation of these isolates with curative doses of PZQ, they showed
      significant less response to the drug in terms of both the drug efficacy (percent
      of worm reduction), and the ED50 (the effective dose that kills 50% of worms).
      Also, stability test was performed on some S. mansoni isolates. This means
      repeated treatment of unsusceptible isolates that have been passed for several
      passages in the lab. and results compared to that of a control susceptible
      isolate (originally taken from a patient cured after a single dose of PZQ). The
      results showed that repeated passage of S. mansoni isolates in the lab. does not
      render them more susceptible to PZQ. Indeed, these resistant isolates showed less
      susceptibility to the drug than before, or at least they retain their original
      level of insusceptibility to PZQ.

PMID- 12214937
TI  - Studies on theileria and babesia infecting live and slaughtered animals in Al
      Arish and El Hasanah, North Sinai Governorate, Egypt.
AB  - During the year 2001, a total of 475 sheep, 200 goats, 135 cattle and 190 camels
      in El Arich city and El Hassanah center were examined for Babesia ovis and
      Theileria ovis. Blood films were taken from the vein of the ear. Meanwhile, the
      animals were examined for tick infestations. B. ovis and Th. ovis were detected
      in 13 (2.7%), and 14 (2.9%) sheep, 14 (7.0%), and 15 (7.5%) goats, 13 (9.6%), and
      11 (8.1%) cattle and 18 (9.5%), and 24 (12.6%) camels respectively. On the other
      hand, double infection was found in 114 (24%) sheep, 51 (25%) goats, 27 (20%)
      cattle and 66 (34.7%) camels. Adult ticks were identified as Rhipicephalus
      appendiculatus, R. bursa, R. turanicus and Haemaphysalis parva on sheep, Hyalomma
      anatolicum excavatum and Haemaphysalis sulcata on goats, Hyalomma lusitanicum on
      cattle and Hyalomma dromedarii, H. impeltatum, H. marginitum and H. a. anatolicum
      on camels. Babesia ovis and/or Theileria ovis were recorded in ticks gut and/or
      salivary glands in R. appendiculatus (20.%), R. bursa (16.7%), R. turanicus
      (10%), Haemaphysalis parva (10%), H. a. excavaium (30.%), H. dromedarii (18%),
      and H. a. anatolicum (6.7%).

PMID- 12214938
TI  - The efficacy of artemether versus quinine in the treatment of cerebral malaria.
AB  - Cerebral malaria remains a major cause of childhood morbidity. Quinine is the
      drug of choice for which resistance is now emerging. A total of 77 children
      admitted to Khartoum Children Emergency Hospital who conform to WHO criteria of
      cerebral malaria were randomly allocated to receive either artemether (1.6 mg/kg
      body wt., repeated after 12 hrs and then daily for four days) or quinine (10
      mg/kg body wt in 10 ml/kg body wt of 5% dextrose in 0.9% saline intravenously.
      Repeated every 8 hrs and changed to oral administration when the child was able
      to drink to finish seven days). Response to therapy was evaluated using fever
      clearance time (FCT), time of regaining consciousness (TRC) and parasite
      clearance time (PCT). The FCT (mean+SD), TRC and PCT for the artemether-treated
      group were 32 (+13) hrs, 21 (+11) hrs and 36 (+18) hrs, respectively, while for
      the quinine-treated group the respective figures were 36 (+18), 26 (+15) hrs and
      41 (+12) hrs. The response to artemether was slightly better than that of
      quinine, but the differences between the two groups were not statistically
      significant. The outcome in terms of cure rate, neurological sequalae and case
      fatality was also comparable.

PMID- 12214939
TI  - Codon usage analysis of Ascaris species influence of base and intercodon
      frequencies on the synonymous codon usage.
AB  - Patterns of codon usage and bias were characterized in the genus Ascaris.
      Furthermore, the influence of base composition and intercodon frequencies on
      codon usage was investigated using freely available analytical software. Results
      showed that A and T were present in the genome at a higher frequency than G and
      C. As well, codons with AT base pairs at the wobble position were used more often
      than those with GC at this site, suggesting that the bias extends to the codon
      level. The presence of T at the intercodon position inhibited the use of codon
      with A at the wobble site. With respect to amino acid frequency, Serine, Leucine,
      and Arginine accounted for a disproportionately large fraction of the overall
      amino acid distribution per gene, implying that the bias was also conserved at
      the protein level.

PMID- 12214940
TI  - Evaluation of IgM-ELISA versus PCR in diagnosis of recent Toxoplasma gondii
      infection.
AB  - Whereas Toxoplasma gondii infection in the immunocompetent adult usually causes
      no serious clinical symptoms, congenital infection can lead to abortion or severe
      disease in the newborn infant. Early diagnosis should be made as soon as possible
      particularly in pregnant women and newborn babies since early treatment can
      minimize fetal sequelae. This work evaluates IgM-ELISA and PCR in diagnosis of
      recent T. gondii infection. The results revealed that PCR detected very recently
      infected cases (23 out of 70 suspected cases) than IgM-ELISA (only 18 cases). The
      combination of both tests may help to improve the sensitivity of diagnosis (45%
      in suspected group) more than either PCR (32.8%) or IgM-ELISA alone (25.7%).

PMID- 12214941
TI  - A histochemical study on the hydatid cyst and electron microscopy of the hydatid
      sand of Echinococcus granulosus.
AB  - The histochemistry of the hydatid cyst wall of E. granulosus from goat and sheep
      were studied. The cyst wall contains a carbohydrate-protein substrate complex,
      collagen and possibly calcium. Calcium is also reported in protoscolices of
      hydatid sand. Tegumental projections on free brood capsules and protoscolices
      were viewed by scanning electron microscope (SEM) and the tegument of
      protoscolices was revealed by transmission electron microscopy (TEM).

PMID- 12214942
TI  - Influence of parasitic life style on the patterns of codon usage and base
      frequencies of Ancylostoma and Necator species.
AB  - Parametric analyses were used to investigate the nucleotide, codon, and amino
      acid composition of coding sequences corresponding to hook-worms. Ancylostoma
      caninum and Necator americanus. Although genomic research has become prevalent
      within the scientific community, few studies have dealt directly with parasitic
      species. Parasites have existed throughout the history of mankind due to their
      wide range of distribution in nature and their ability to evade immune detection.
      An AT nucleotide bias was identified in both A. caninum and N. americanus
      sequences. A similar AT bias was also identified in both datasets when
      considering relative synonymous codon usage. However, the codon bias was much
      more pronounced in N. americanus as compared to A. caninum. Bias was also present
      at the amino acid level, and appeared to be partially independent of the
      nucleotide-based biases. Analysis of parasite genomes will facilitate the
      development of vaccines against larval forms of parasites. Moreover, the
      examination of the parasite genes in general, will allow for a more in-depth
      understanding of the evolution of the parasites and parasitism.

PMID- 12214943
TI  - The bleaching of tetracycline-stained teeth.

PMID- 12214944
TI  - LED curing lights.

PMID- 12214945
TI  - The milled bar-retained removable bridge implant-supported prosthesis: a
      treatment alternative for the edentulous maxilla.
AB  - Restoration of the edentulous jaw with dental implants can be achieved using
      either an implant-supported prosthesis, such as a fixed bridge, or an implant
      retained prosthesis, such as a traditional overdenture. The implant-retained
      prostheses use edentulous ridges as primary stress-bearing regions, and through
      stress-breaking mechanisms, the implants are not loaded during function. However,
      the success rates of maxillary overdentures do not appear to be as good as for
      mandibular overdentures; this may be attributable to the adverse loading
      conditions, short implant length, poor quality of bone, number of implants used,
      flexible bar design, or poor treatment planning. Many articles have also
      described the numerous problems and multiple visits required in maintaining a
      traditional bar-retained overdenture restoration, often making it more expensive
      in the long term than a fixed restoration. The milled bar implant-supported
      prosthesis offers the benefits of both fixed and removable restorations. Its
      infrastructure provides the same rigidity as the fixed restoration, owing to the
      precise fit to the superstructure, which is removable, to promote adequate access
      for hygiene, yet it still provides lip support and maintains close contact with
      the soft tissues. These advantages enhance phonetics, esthetics, correct lip
      support, maintenance, and patient comfort.

PMID- 12214946
TI  - Restorative and Invisalign: a new approach.
AB  - This case report describes an interdisciplinary treatment approach using the
      Invisalign System (Align Technology, Inc., Santa Clara, California) for
      orthodontics in combination with restorative dentistry. This combined approach
      was selected for an optimum esthetic and functional result. This case report
      demonstrates how a restorative case can be improved with prerestorative
      orthodontic alignment. The Invisalign System was used for opening the bite
      anteriorly, space distribution, and midline correction. The restorative dentistry
      procedures involved veneering to enhance the maxillary incisor length-to-width
      ratio and provide anterior guidance. The cosmetic alternative treatment modality
      to conventional fixed orthodontics allowed the clinician to accomplish the
      prerestorative orthodontic goals to help meet the desires of an esthetically
      conscientious patient.

PMID- 12214947
TI  - Spline implant prospective multicenter study: interim report on prosthetic screw
      stability in partially edentulous patients.
AB  - Loosening of implant abutment and prosthesis screws during functional loading is
      an industry-wide phenomenon that is especially well documented with the external
      hexagon implant connection. Although numerous efforts to reduce or eliminate
      screw loosening have been attempted, the problem still persists, especially with
      implant restorations in the partially edentulous patient. In 1992, the spline was
      developed as an alternative to the external hexagon implant-abutment connection.
      A prospective multicenter study was begun in 1996 to evaluate the abutment and
      prosthesis screw joint stability of Spline dental implants (Centerpulse Dental
      Division, Carlsbad, California) over 5 years of post-loading clinical follow-up.
      From October 1996 to December 2000, 73 partially edentulous patients were
      consecutively treated with 113 Spline implants placed in two private dental
      practices. Three patients with 1 implant each withdrew from the study for various
      reasons; of the remaining 110 implants in 70 patients who continued in the study,
      82% (n = 90) were placed between 1997 and 1998. No cases of abutment or
      prosthesis screw loosening occurred with up to 54 months (mean = 38.95 mo; range,
      3-54 mo; mode, 20 mo) of post-loading clinical follow-up. These interim findings
      of the ongoing study suggest that Spline dental implants may provide a stable
      prosthetic connection in partially edentulous cases during short-term clinical
      follow-up.

PMID- 12214948
TI  - Effects of 10% carbamide peroxide on the enamel surface morphology: a scanning
      electron microscopy study.
AB  - BACKGROUND: Several studies have been published about the effect of carbamide
      peroxide on enamel surface morphology. However, only a few studies have been
      carried out under intraoral conditions. The purpose of this study was to
      investigate the effect of two commercially available 10% carbamide peroxide
      bleaching products (Colgate Platinum and Starbrite) on the enamel surface
      morphology under intraoral conditions. MATERIALS AND METHODS: Twenty-four
      subjects were divided into two groups and assigned a product to use for 2 weeks.
      Epoxy resin replicas obtained from the maxillary right central incisors of the
      subjects before, immediately after, and 3 months after the bleaching procedure
      were examined under a scanning electron microscope. RESULTS: Immediately after
      the bleaching procedure, the surface porosity of enamel had increased in the
      Colgate Platinum group, whereas erosive surface alterations were observed in the
      Starbrite group. At 3 months, the surface morphology of enamel in the Colgate
      Platinum group was similar to the untreated enamel surface. In the Starbrite
      group, erosive defects on the enamel surface had decreased within 3 months, and
      the appearance of the enamel surface was almost the same as the untreated enamel.
      CONCLUSION: Even though both bleaching agents caused alterations in the surface
      morphology of enamel, these alterations were reversed within 3 months following
      treatment. CLINICAL SIGNIFICANCE: The results of this study suggest that 10%
      carbamide peroxide bleaching products cause alterations in enamel surface
      morphology immediately after bleaching, and the degree of these alterations
      depends on the brand of bleaching agent and duration of application time.
      However, these alterations revert to almost normal within 3 months.

PMID- 12214950
TI  - Tooth-whitening toothpastes.

PMID- 12214949
TI  - Effects of four prophylaxis pastes on surface roughness of a composite, a hybrid
      ionomer, and a compomer restorative material.
AB  - PURPOSE: This study was undertaken to compare the effects of three prophylaxis
      pastes (Nupro with coarse, medium, or fine pumice) with a new paste (Clinpro with
      perlite) on the surface roughness of a resin composite (Dyract AP), a hybrid
      ionomer (Fuji II LC), and a compomer (TPH Spectrum). MATERIALS AND METHODS:
      Twenty disks (2 mm thick x 10 mm in diameter) of each material were prepared in
      split molds and stored for 24 hours at 37 degrees C in a 100% relative humidity
      humidistat. Baseline Mylar surface roughness values were determined. A single
      operator polished each specimen for 10 seconds with each paste. Five tracings of
      each specimen of surface roughness (Ra, microm) were made using a surface
      profilometer. Means and standard deviations were calculated, and analyzed by two
      way analysis of variance (three restorative materials and four prophylaxis pastes
      as factors) and compared using Tukey-Kramer intervals calculated at the 0.05
      level of significance. RESULTS: Analysis of variance showed significant
      differences among restorative materials (after polishing) and prophylaxis
      polishing agents. Tukey-Kramer intervals for comparisons were 0.04 and 0.05
      microm, respectively. All polishing agents produced significant increased
      roughness compared with baseline, yielding the following results (X + SD, microm)
      for the three restorative materials (Fuji II LC, TPH Spectrum, Dyract AP):
      perlite, 0.16 +/- 0.07, 0.28 +/- 0.26, 0.79 +/- 0.64; course pumice, 0.36 +/-
      0.17, 0.48 +/- 0.25, 0.88 +/- 0.46; medium pumice, 0.26 +/- 0.10, 0.35 +/- 0.30,
      0.46 +/- 0.21; and fine pumice, 0.16 +/- 0.06, 0.34 +/- 0.30, 0.42 +/- 0.24).
      Fine pumice and perlite produced the least roughness on the hybrid ionomer,
      medium and fine pumice on the resin composite, and perlite on the compomer.
      CLINICAL SIGNIFICANCE: Since prophylaxis pastes have the potential to increase
      the surface roughness of resin composite, hybrid ionomer, and compomer
      restorative materials, routine polishing during prophylaxis should be avoided.

PMID- 12214951
TI  - Sensation seeking and detection of risky road signals: a developmental
      perspective.
AB  - The relevance of the construct of sensation seeking, particularly the motivation
      to seek thrill and adventure and to avoid boredom, to detection of danger on the
      road, in particular choices made in conditions of road dilemmas (e.g. road
      crossing and amber-light), was examined. 412 participants, males and females,
      from three age groups--7, 13 and 22--completed Zuckerman's test of sensation
      seeking and were exposed to the following experiments: Virtual driving, road
      crossing and go-carting. In each experiment, participants were exposed
      individually to a series of road dilemmas, constructed according to the paradigm
      of signal detection. In each dilemma, a dichotomous choice was made: To do or not
      to do. Age- and gender-dependent responses and connections were obtained. Most
      noticeable is a risky shift in males' detection responses and an inverse trend in
      females.

PMID- 12214952
TI  - Bridge strike reduction: optimising the design of markings.
AB  - Cases of high-sided vehicles striking low bridges is a large problem in many
      countries, especially the UK. This paper describes an experiment to evaluate a
      new design of markings for low bridges. A full size bridge was constructed which
      was capable of having its overhead clearance adjusted. Subjects sat in a truck
      cab as it drove towards the bridge and were asked to judge whether the vehicle
      could pass safely under the bridge. The main objective of the research was to
      determine whether marking the bridge with a newly devised experimental marking
      would result in more cautious decisions from subjects regarding whether or not
      the experimental bridge structure could be passed under safely compared with the
      currently used UK bridge marking standard. The results show that the type of
      bridge marking influenced the level of caution associated with decisions
      regarding bridge navigation, with the new marking design producing the most
      cautious decisions for the two different bridge heights used, at all distances
      away from the bridge structure. Additionally, the distance before the bridge at
      which decisions were given had an effect on the level of caution associated with
      decisions regarding bridge navigation (the closer to the bridge, the more
      cautious the decisions became, irrespective of the marking design). The
      implications of these results for reducing the number of bridge strikes are
      discussed.

PMID- 12214953
TI  - Driving simulator validation for speed research.
AB  - The behavioral validation of an advanced driving simulator for its use in
      evaluating speeding countermeasures was performed for mean speed. Using mature
      drivers, 24 participants drove an instrumented car and 20 participants drove the
      simulator in two separate experiments. Participants drove on roads which
      contained transverse rumble strips at three sites, as well as three equivalent
      control sites. The three pairs of sites involved deceleration, and were the
      approaches to stop sign intersections, right curves, and left curves. Numerical
      correspondence (absolute validity), relative correspondence (or validity), and
      interactive (or dynamic) relative validity were analyzed, the latter using
      correlations developed from canonical correlation. Participants reacted to the
      rumble strips, in relation to their deceleration pattern on the control road, in
      very similar ways in both the instrumented car and simulator experiments,
      establishing the relative validities. However, participants generally drove
      faster in the instrumented car than the simulator, resulting in absolute validity
      not being established.

PMID- 12214954
TI  - Drivers' response to the installation of road lighting. An economic
      interpretation.
AB  - An economic model of drivers' behaviour is introduced in order to explain
      recently published empirical findings telling us that road lighting increases
      speed, decreases concentration and reduces accidents. The model, combined with
      the empirical results, indicate that drivers perceive speed and concentration as
      complementary safety variables, while common sense suggests that speed and
      concentration influence real accident rate as substitutable safety means. If this
      holds, a positive but concave relationship between subjective and objective risks
      exists, which means that as the objective accident risk rises, it has less
      influence on perceived risk.

PMID- 12214955
TI  - Factors influential in making an injury severity difference to older drivers
      involved in fixed object-passenger car crashes.
AB  - To identify factors influencing severity of injury to older drivers in fixed
      object-passenger car crashes, two sets of sequential binary logistic regression
      models were developed. The dependent variable in one set of models was driver
      injury severity, whereas for the other it was the crash severity (most severe
      injury in the crash). For each set of models, crash or injury severity was varied
      from the least severity level (no injury) to the highest severity level
      (fatality) and vice versa. The source of data was police crash reports from the
      state of Florida. The model with the best fitting and highest predictive
      capability was used to identify the influence of roadway, environmental, vehicle,
      and driver related factors on severity. Travel speed, restraint device usage,
      point of impact, use of alcohol and drugs, personal condition, gender, whether
      the driver is at fault, urban/rural nature and grade/curve existence at the crash
      location were identified as the important factors for making an injury severity
      difference to older drivers involved in single vehicle crashes.

PMID- 12214956
TI  - Relationship between crash rate and hourly traffic flow on interurban motorways.
AB  - This paper describes the relationship between crash incidence rates and hourly
      traffic volume and discusses the influence of traffic on crash severity, based on
      observations made on 2000 km of French interurban motorways over 2 years.
      Incidence rates involving property damage-only crashes and injury-crashes are
      highest when traffic is lightest (under 400 vehicles/h). These incidence rates
      are at their lowest when traffic flows at a rate of 1000-1500 vehicles/h. For
      heavier traffic flows, crash incidence rates increase steadily as traffic
      increases on 2- and 3-lane motorways and inflect on 2-lane motorways when traffic
      increases to a level of 3000 vehicles/h. For an equivalent light traffic level,
      the number of crashes is higher on three-lane than on 2-lane motorways and higher
      at weekends (when truck traffic is restricted) than on weekdays. In heavy
      traffic, the number of crashes is higher on weekdays. We found no significant
      difference between the number of daytime and night-time crashes, whatever the
      traffic. No difference was observed in crash severity by number of lanes or
      period in the week for a given level of traffic. However, severity is greater at
      night and when hourly traffic is light. Compared to the number of vehicles on the
      road, light traffic is a safety problem in terms of frequency and severity, and
      road safety campaigns targeting motorway users to influence their behavior in
      these driving conditions should be introduced.

PMID- 12214957
TI  - The importance of confounding in observational before-and-after studies of road
      safety measures.
AB  - This paper discusses the importance of confounding in observational before-and
      after studies of road safety measures. The importance of the approach taken to
      controlling for confounding factors is shown by means of examples. It is shown
      that the size of the effect on accidents attributed to a road safety measure can
      be profoundly affected by which confounding factors are controlled for in an
      evaluation study, and the way this is done. Simple before-and-after studies, not
      controlling for any confounding factors should never be trusted and are likely to
      overstate the effects of road safety measures.

PMID- 12214958
TI  - Characteristics of low speed accidents with buses in public transport.
AB  - Low-speed accidents with buses in public transport in the city of Uppsala during
      the years 1986-2000 are coded in 17 variables concerning mainly physical
      properties of the accident. The taxonomy uses classifications from existing
      schemes, but some are altered and some new are added to capture common features
      of reports of bus accidents in this population. It is found that side contacts
      and singles are the most common accidents, and that more than a quarter of all
      accident involvements occurs at bus stops. Inter-rater reliability calculations
      for the categories show that all except one have reliabilities above 80%. The
      level of internal validity, calculated as agreement of frequencies between time
      periods, is acceptable, despite many possible sources of change and bias. It is
      argued that the validity of this database far exceeds that of the, for research
      purposes normally used, non-company self-reports, state- and police-archives, due
      to more extensive reporting and corroborating evidence. The practical usefulness
      of these results and accident taxonomies in general is discussed.

PMID- 12214959
TI  - How the presence of passengers influences the risk of a collision with another
      vehicle.
AB  - The risk of a collision with another vehicle due to the presence of passengers is
      analysed in detail in a large sample of accidents from Mittelfranken, Germany,
      from the years 1984 to 1997. Using a responsibility analysis, the overall effect
      of the presence of passengers and the influence of modifying variables is
      examined. While a general protective effect of the presence of passengers is
      found, this is reduced in young drivers, during darkness, in slow traffic and at
      crossroads, especially when disregarding the right of way and passing a car.
      These findings are interpreted as a general positive effect of the presence of
      passengers who influence the driver's behaviour towards more cautious and thus
      safer driving behaviour. However, passengers may also distract drivers' attention
      in an amount which cannot be compensated for in all situations and by all drivers
      by cautious driving. Besides educational measure, a potential solution to this
      problem may be driver assistance systems which give an adapted kind of support
      when passengers are present.

PMID- 12214960
TI  - Individual differences during driver secondary task performance: verbal protocol
      and visual allocation findings.
AB  - This paper reports a study in which visual allocation and verbal reports were
      recorded to determine individual differences in drivers conducting in-vehicle
      tasks. Participants drove a simulated route whilst conducting pre-defined tasks
      using the in-vehicle entertainment system. Tasks of varying complexity were
      presented to the participants. Licensed (experienced) drivers made significantly
      more verbal reports relating to road signs and markings, vehicles, scenery in
      general and vehicle operations; than did unlicensed (novices). No significant
      difference was found between expert and novice drivers when reporting in-car
      entertainment system related utterances. Surprising gender differences were also
      found. Males drove faster, with greater variance, and made more utterances in
      identified categories. Females were found to make significantly less verbal
      reports during secondary task performance. The difference in results obtained
      between expert and novices may imply that novices need to use their attention
      capacity to focus on the skill of driving, whereas experts through experience,
      have automated this skill and can use their attention capacity to more
      effectively during primary tasks. Results suggest that expert drivers are not
      necessarily experts at undertaking secondary tasks.

PMID- 12214961
TI  - Biomechanical analyses of whiplash injuries using an experimental model.
AB  - Neck pain and headaches are the two most common symptoms of whiplash. The working
      hypothesis is that pain originates from excessive motions in the upper and lower
      cervical segments. The research design used an intact human cadaver head-neck
      complex as an experimental model. The intact head-neck preparation was fixed at
      the thoracic end with the head unconstrained. Retroreflective targets were placed
      on the mastoid process, anterior regions of the vertebral bodies, and lateral
      masses at every spinal level. Whiplash loading was delivered using a mini-sled
      pendulum device. A six-axis load cell and an accelerometer were attached to the
      inferior fixation of the specimen. High-speed video cameras were used to obtain
      the kinematics. During the initial stages of loading, a transient decoupling of
      the head occurs with respect to the neck exhibiting a lag of the cranium. The
      upper cervical spine-head undergoes local flexion concomitant with a lag of the
      head while the lower column is in local extension. This establishes a reverse
      curvature to the head-neck complex. With continuing application of whiplash
      loading, the inertia of the head catches up with the neck. Later, the entire head
      neck complex is under an extension mode with a single extension curvature. The
      lower cervical facet joint kinematics demonstrates varying local compression and
      sliding. While the anterior- and posterior-most regions of the facet joint slide,
      the posterior-most region of the joint compresses more than the anterior-most
      region. These varying kinematics at the two ends of the facet joint result in a
      pinching mechanism. Excessive flexion of the posterior upper cervical regions can
      be correlated to headaches. The pinching mechanism of the facet joints can be
      correlated to neck pain. The kinematics of the soft tissue-related structures
      explain the mechanism of these common whiplash associated disorders.

PMID- 12214962
TI  - A model of traffic crashes in New Zealand.
AB  - The aim of this study was to examine the changes in the trend and seasonal
      patterns in fatal crashes in New Zealand in relation to changes in economic
      conditions between 1970 and 1994. The Harvey and Durbin (Journal of the Royal
      Statistical Society 149 (3) (1986) 187-227) structural time series model (STSM),
      an 'unobserved components' class of model, was used to estimate models for
      quarterly fatal traffic crashes. The dependent variable was modelled as the
      number of crashes and three variants of the crash rate (crashes per 10,000 km
      travelled, crashes per 1,000 vehicles, and crashes per 1000 population).
      Independent variables included in the models were unemployment rate (UER), real
      gross domestic product per capita, the proportion of motorcycles, the proportion
      of young males in the population, alcohol consumption per capita, the open road
      speed limit, and dummy variables for the 1973 and 1979 oil crises and seat belt
      wearing laws. UERs, real GDP per capita, and alcohol consumption were all
      significant and important factors in explaining the short-run dynamics of the
      models. In the long-run, real GDP per capita was directly related to the number
      of crashes but after controlling for distance travelled was not significant. This
      suggests increases in income are associated with a short-run reduction in risk
      but increases in exposure to a crash (i.e. distance travelled) in the long-run. A
      1% increase in the open road speed limit was associated with a long-run 0.5%
      increase in fatal crashes. Substantial reductions in fatal crashes were
      associated with the 1979 oil crisis and seat belt wearing laws. The 1984
      universal seat belt wearing law was associated with a sustained 15.6% reduction
      in fatal crashes. These road policy factors appeared to have a greater influence
      on crashes than the role of demographic and economic factors.

PMID- 12214963
TI  - The relationship between liquor outlet density and injury and violence in New
      Mexico.
AB  - This study used an ecologic design based on data from 1990 to 1994 gathered from
      forensic, vital statistic, census, law enforcement and liquor licensing agencies
      to assess the relationship between liquor outlet density and alcohol-related
      health outcomes in New Mexico. Linear regression models show that suicide,
      alcohol-related crash, and alcohol-related crash fatality (adjusted for age, sex,
      and minority status) are significantly associated with liquor outlet density.
      Data also show that, compared with the first tertile, suicide and alcohol-related
      crash rates increase about 50% and the alcohol-related crash fatality rate two
      fold with the third tertile of liquor outlet density. Greater availability of
      liquor outlets is associated with higher rates of suicide, alcohol-related crash,
      and alcohol-related crash fatality.

PMID- 12214964
TI  - Epidemiological data and ranking home and leisure accidents for priority-setting.
AB  - OBJECTIVE: To determine how to use the multitude of available epidemiological
      data to rank accidents for prioritisation of prevention. METHODS: A stepwise
      method to rank accidents for priority-setting at any time is proposed. The first
      step is to determine the overall objectives of injury prevention. Based on these
      objectives, the relevant epidemiological criteria are determined. These criteria
      need to be weighed by experts in such a way that these weights can be used for
      every new cycle of priority-setting. Thus, every time the method is applied:
      first, the relevant types of accidents are identified; second, the
      epidemiological criteria are determined per type of accident; and third, the
      types of accidents are ranked by means of standardised weights per criterion. The
      proposed indirect method is illustrated by an empirical example. The results were
      compared with a direct method, i.e. ranking by an expert panel. RESULTS: In the
      pilot, we ranked four age groups of victims of a home and leisure accident: 0-4,
      4-19 and 20-54 years of age, and victims aged 55 years or older. The resulting
      rankings differ largely per application; number one are victims older than 55
      years or those of 20-54 years. CONCLUSIONS: The proposed method enables a
      structured, transparent way to set priorities for home and leisure accidents. It
      is a promising method, although further development is clearly necessary, based
      on the actual application of the model.

PMID- 12214965
TI  - Pedestrian crashes in Washington, DC and Baltimore.
AB  - Police crash reports were obtained for pedestrian-motor vehicle crashes in
      Washington, DC (N = 852) and Baltimore (N = 1234) for the year 1998. Reports were
      coded using procedures developed and applied in these two cities during the
      1970s, including the determination of pedestrian crash type, primary
      precipitating factor, and culpability. Results indicated substantial differences
      between crash patterns observed during the 1970s and those observed during 1998.
      Midblock dart-dash crashes, which typically involve a precipitating factor or
      critical error by a child pedestrian, decreased (from 37% to 15% in Washington).
      Across all crashes in both cities, the number of drivers who made a critical
      error leading to the crash was nearly equivalent to the number of pedestrians who
      made a critical error. Overall, pedestrians were slightly more likely to be
      judged culpable (50% vs. 39%). Turning vehicle crashes, which typically involve a
      driver's failure to grant a pedestrian the right of way at a signalized
      intersection, increased (from 9% to 25% in Washington). Countermeasures to reduce
      the number of pedestrians hit by turning vehicles are discussed.

PMID- 12214966
TI  - Driving performance of drivers with impaired central visual field acuity.
AB  - This study investigated the performance of drivers with impairment to their
      central field of vision but with normal peripheral vision, due to retinoschisis,
      in a safety critical driving tasks. The performance of five male drivers with
      impaired vision (VA 0.2), aged between 40 and 50 years, all with more than
      250,000 km life-time driving experience and a good safety record, and five normal
      vision controls, matched by gender, age, driving experience and safety record,
      were tested in 40 km/h city traffic and in a motorway car following situation.
      All participants displayed appropriate driving ability in city traffic and all
      were able to detect and respond adequately to a conflicting 'stunt pedestrian'
      and 'stunt cyclist' situation. There were no apparent differences between the
      drivers with impaired vision and those with normal vision. In the car following
      situation, the participants drove at 80 km/h, 50 m behind a lead car, on a 30 km
      section of motorway in normal traffic. During each trial, the lead car started to
      decelerate at an average of 0.53 m/s2 while the participant either looked at the
      car in front (control) or performed a memory and addition task (non-visual
      attention) while looking at the car in front. The participants were required to
      press the brake pedal when they noticed a decrease in headway. The participant's
      brake reaction time to the onset of the lead car's brake lights was also tested.
      The drivers with impaired vision were significantly slower, by 0.2 s, in
      detecting the onset of brake lights than the normal vision drivers. Their headway
      closure detection was 0.7 s slower than normal vision drivers, but this
      difference was not statistically significant in this small data. In spite of some
      impairment in car following (central vision task), the results together with the
      clean record of these drivers with retinoschisis support the idea that visual
      acuity of 0.5 (the European Union norm) is not a necessary prerequisite for safe
      driving.

PMID- 12214967
TI  - Waste management plays an integral role in our lives.

PMID- 12214968
TI  - Treatment of simulated Reactive Yellow 22 (azo) dye effluents using Spirogyra
      species.
AB  - The potential of commonly available green algae belonging to Spirogyra species
      was investigated as viable biomaterials for biological treatment of simulated
      synthetic azo dye (Reactive Yellow 22) effluents. The results obtained from the
      batch experiments revealed the ability of the algal species in removing the dye
      colour and was dependent both on the dye concentration and algal biomass. Maximum
      dye colour removal was observed on the third day for all the system conditions.
      Monitoring of ORP values helped to understand the overlying biochemical mechanism
      of algal-dye system. Based upon the results, the dye-algal treatment mechanism
      was attributed to biosorption (sorption of dye molecules over the surface of
      algal cells), bioconversion (diffusion of dye molecules into the algal cells and
      subsequent conversion) and biocoagulation (coagulation of dye molecules present
      in the aqueous phase onto the biopolymers released as metabolic intermediates
      during metabolic conversion of dye and subsequent settlement).

PMID- 12214969
TI  - Ecotoxicological assessment of leachates from MSWI bottom ashes.
AB  - In this paper, chemical and ecotoxicological data of leachates from bottom ashes
      collected in different Municipal Solid Waste Incinerators (MSWI) are shown. The
      bottom ashes were collected in Belgium (three incinerators--samples B1 to B3),
      France, Germany, Italy and United Kingdom (one incinerator in each country-
      samples F1, D1, I1 and UK1, respectively). Both chemical and ecotoxicological
      characterizations of leachates were done on the framework of the European
      Directive 91/689/EEC and the European Council Decision 94/904/EC. This work was
      carried out under the European project called Valomat, which was supported by the
      European Commission through Brite-Euram III program. Twenty-one inorganic
      parameters were analyzed. The ecotoxicological assays were done under standard
      laboratory conditions, using the bacterium Photobacterium phosphoreum, the
      freshwater alga Pseudokirchneriella subcapitata, the crustacean Daphnia magna and
      the vegetable Lactuca sativa. Chemical data varied from sample to sample. Similar
      results were obtained in biological assays. The samples can be classified as
      ecotoxic/hazardous according to the French proposal for a Criterion and
      Evaluation Methods of Waste Ecotoxicity (CEMWE) and the German regulation on
      Hazardous Waste Classification (HWC). However, samples B1, B2, B3 and D1 comply
      the maximum limits for direct valorization category defined in the French
      Classification of Bottom Ashes based on their Polluting Potential (CBAPP). Sample
      B1 presented the lowest level of ecotoxicity, being considered as the most
      interesting to be used in the development of new materials for civil engineering
      works.

PMID- 12214970
TI  - Adsorption of phenol and m-chlorophenol on organobentonites and repeated thermal
      regeneration.
AB  - Experimental investigations were conducted on the adsorption characteristics of
      phenol and m-chlorophenol by organobentonites. The organobentonites were prepared
      by modifying natural bentonite with various quaternary ammonium salts including
      tetramethylammonium bromide, hexadecyltrimethylammonium bromide, benzyl
      triethylammonium bromide, tetraethylammonium bromide and cetylpyridinium bromide.
      The adsorption characteristics of phenol and chlorophenol by these
      organobentonites were examined in detail. The empirical Freundlich isotherm was
      found to describe well the equilibrium adsorption data. Thermal regeneration of
      spent organobentonites was also investigated and operating conditions of 200
      degrees C and 2 h heating were found to yield very good results.

PMID- 12214971
TI  - Assessment of the leaching of metallic elements in the technology of
      solidification in aqueous solution.
AB  - Results are presented of experiments performed to optimize the
      solidification/stabilization system for metallic elements in aqueous solution.
      This system involves mixing cement and a solution of metallic elements in a
      conventional mixer: the paste thus obtained is transferred drop by drop into a
      recipient filled with an aqueous solution of NaOH at 20% by weight, in which it
      solidifies immediately. The separate use of chloride solutions of Li+, Cr3+, Pb2+
      and Zn2+ makes it possible to obtain granules displaying various levels of
      compressive strength. Three different inertization matrices were used in the
      experiments, the first consisting solely of Portland cement, the second of
      Portland cement and a superplasticizer additive, and the third of Portland cement
      partially replaced with silica-fume and superplasticizer. The results of the
      tests performed showed a very low level of leaching into the alkaline
      solidification solution for Cr3+, the quantity leached being under 2% as against
      higher levels for the other metallic elements. For all the considered elements,
      the best results were obtained by using silica-fume in the inertization matrix.

PMID- 12214972
TI  - Wet oxidation: a pre-treatment procedure for sludge.
AB  - Wet oxidation process is specially effective for wastes with a high organic
      matter which can not be removed by conventional treatment methods. The digested
      and raw activated sludges of PAKMAYA yeast factory are treated by wet oxidation
      process. The liquid-phase organic matter concentration [as total organic carbon
      (TOC)] was increased by 16.5% in 10 min during the wet oxidation in the presence
      of Cu as catalyst and H2O2. Lenghtening the period of the wet oxidation, the TOC
      concentration was increased by 66% in 120 min. The biodegradability of the sludge
      after wet oxidation process was also examined. A very little development in the
      biodegradability was observed, when wet oxidation was applied as pre-treatment to
      the digested sludge (5% decrease as TOC, in the presence of Cu catalyst and
      H2O2). However, in the case of digestion of the raw sludge after the application
      of wet oxidation, the biodegradability increased significantly (approximately
      75%, as TOC). Moreover, wet oxidation improved the ability of settling of sludge
      solids, as well as enhancing the treatment efficiency. Finally, the volume of
      settled solids was decreased by 80% in the presence of Cu and H2O2. NH3+-N, NO2(
      )-N and NO3(-)-N concentrations in the supernatant decreased with the wet
      oxidation. pH value of the sludge increased from 6.6 to 7.8-8.0. Since stable
      sludge was taken from the digester where the nitrification process was
      progressing, a decrease in the nitrite concentration, with an increase in nitrate
      was observed in the digestion continuing after the wet oxidation pre-treatment.
      However, in the raw activated sludge, there was a nitrite formation only in the
      non-pretreated sludge.

PMID- 12214973
TI  - Solutions to the problem of waste deposition at a coal-fired power plant.
AB  - This paper deals with the impact on the environment of the combined operation of
      a power plant and a coal mine located in Velenje, Slovenia. The consequences of
      intensive deep underground mining are the sinking of the surface and the filling
      up of the emerging hollows with water. As far as the various consequences of coal
      combustion are concerned, only the harmful effects of the surface deposition of
      ash and slag are discussed, with the poisoning of the lake and the river water
      being considered the most harmful. The integrated system of waste treatment at
      the power plant is presented. The idea of the system is to use the waste
      materials such as ash, slag, gypsum, contaminated water, etc. as the building
      materials or to apply them in the process of improving the ash dump and the
      environment. The system needs to be closed as much as possible, so that the waste
      cannot influence the surroundings of the dump. The physical and chemical
      properties of the waste materials from the power plant, the results of ecological
      measurements and the impact of the ecological damage are presented. In addition,
      we present: a description of the applied methods; the activities and the
      technical measures; the obtained results and the difficulties; and the problems
      that need to be overcome in order to normalise the ecological conditions.

PMID- 12214974
TI  - Improvement of nuclide leaching resistance of paraffin waste form with low
      density polyethylene.
AB  - Low-level liquid borate wastes have been immobilized with paraffin wax using a
      concentrate waste drying system (CWDS) in Korean nuclear power plants. The
      possibility for improving chemical durability of paraffin waste form was
      suggested in this study. A small amount of low density polyethylene (LDPE) was
      added to increase the leaching resistance of the existing paraffin waste form.
      The influence of LDPE on the leaching behavior of waste form was investigated by
      performing leaching test according to ANSI/ANS-16.1 procedure during 325 days. It
      was observed that the leaching of nuclides immobilized within paraffin waste form
      made a marked reduction although little content of LDPE was added to waste form.
      The acceptance criteria of paraffin waste form associated with leachability index
      (LI) and compressive strength after the leaching test were fully satisfied with
      the help of LDPE.

PMID- 12214975
TI  - Potential use of lignite fly ash for the control of acid generation from
      sulphidic wastes.
AB  - In the present paper, the potential use of lignite fly ash in the control of acid
      generation from sulphidic tailings disposed of at Lavrion, Greece was studied.
      Long-term laboratory column kinetic tests were performed on tailings containing
      27% S, which were homogeneously mixed with various amounts of fly ash, ranging
      from 10 to 63% w/w. The drainage quality of the columns was monitored over a test
      period of 600 days. Chemical and mineralogical characterisation of column solid
      residues was performed after a 270-day test period. The hydraulic conductivity of
      the mixtures was also measured to evaluate the potential of fly ash to form a low
      permeability layer. Based on the results, the addition of fly ash to sulphidic
      tailings, even at the lower amount, increased the pH of the drainage at values of
      8.6-10.0 and decreased the dissolved concentrations of contaminants, mainly Zn
      and Mn, to values that meet the European regulatory limits for potable water.
      Higher fly ash addition to tailings, at amounts of 31 and 63% w/w also reduced
      the water permeability of material from 1.2 x 10(-5) cm/sec to 3 x 10(-7) and 2.5
      x 10(-8) m/s, respectively.

PMID- 12214976
TI  - Local and interregional economic analysis of large US Department of Energy waste
      management projects.
AB  - An economic simulation model was used to understand the local and interregional
      economic impacts of four alternative waste management technologies proposed for
      the US Department of Energy's Savannah River nuclear weapons site. The
      simulations of the four technologies, each of which will cost at least a billion
      dollars, were done for the period 2000-2015. The analyses show that differences
      in project costs are not directly reflected in local economic impacts because of
      differences among the technologies during the design, testing and construction
      phases; differences in locations where the design and pilot-testing would occur;
      and choices about how any of the technologies would be funded.

PMID- 12214977
TI  - Phosphogypsum chemistry under highly anoxic conditions.
AB  - Phosphogypsum (PG), primary byproduct from phosphoric acid production, is
      accumulated in large stockpiles and occupies vast areas of land. Contaminants
      emanating from PG stacks can impact the environment including waterbodies. The
      major constraint for PG use in the environment is the presence of metals in high
      concentrations. Reduction of sulfate found in PG and significance of sulfide
      production in reducing aqueous concentrations of toxic metals were studied.
      Mississippi River alluvial sediment amended with PG was equilibrated under
      controlled redox (-250 mV) and pH (5.5, 6.5, and 7.5) conditions. Phosphogypsum
      addition resulted in a large increase in sulfide levels in sediment suspensions.
      As a result, the solubility of spiked heavy metals (Cd and Cr, 100 and 1000 mg
      kg(-1)) and natural trace elements (As, Ba, and Cd) was significantly reduced by
      precipitation as insoluble sulfides. Sediment pH also influenced sulfate
      reduction and sulfide formation in both PG-amended and control sediment. Low
      sediment pH (5.5) resulted in the highest release of all studied metals and
      sulfate into sediment solution. This study indicates that if PG or PG-products
      are placed in neutral to alkaline sediments/soils and/or reducing environments,
      metals released at toxic levels should be of little concern to the wetland
      environment.

PMID- 12214978
TI  - Bioleaching of zinc and aluminium from industrial waste sludges by means of
      Thiobacillus ferrooxidans.
AB  - Biological solubilisation of heavy metals contained in two different kinds of
      industrial wastes was performed in batches employing a strain of Thiobacillus
      ferroxidans. The wastes tested were: a dust coming from the iron-manganese alloy
      production in an electric furnace (sludge 1) and a sludge coming from a process
      treatment plant of aluminium anodic oxidation (sludge 2). The experimental
      results pointed out the ability of the used strain to maintain the environment,
      that initially has a pH about 8, at strongly acid conditions (pH 2.5-3.5),
      producing sulphuric acid that is the chemical agent responsible for the metals
      solubilisation. At wastes initial concentration of 1%, the percentage of
      solubilised metals was 76 and 78% for the wastes 1 and 2, respectively, but the
      lag phase was considerably longer for sludge 2 than for sludge 1, indicating a
      different affinity of microorganisms for the solid phase. Increasing the initial
      slurry concentration, the percentage of removed metal reached 72-73% for the
      sludge 1, while in case of sludge 2, the total amount of solubilized metal
      progressively decreased. Two kinetic models are proposed to describe the trends
      of metals solubilization curves.

PMID- 12214979
TI  - Prioritising objectives for waste reprocessing: a case study in secondary lead
      refining.
AB  - Secondary lead refining produces a sulphidic slag that also contains varying
      quantities of lead. Initially, the objectives of this project were to treat the
      slag in order to recover the valuable lead as well as to render the slag
      environmentally benign. However, in keeping with the principles of clean
      technology and, specifically, the approach of clean production, the project was
      redefined with the following priorities: waste characterisation; waste
      minimisation through process improvement; waste modification; identification of
      slag treatment methods. Characterisation of the waste facilitated an overall
      process understanding and aided in identifying process deficiencies. Process
      improvement was aimed at reducing both the quantity of slag produced as well as
      the lead loss to the slag. Waste characterisation combined with local hazardous
      waste regulations enabled desirable waste modifications to be identified. These
      waste adaptations were implemented through process modification. Lastly,
      treatment methods for the slag were identified.

PMID- 12214980
TI  - Spontaneous combustion of shale spoils at a sanitary landfill.
AB  - Shale deposits excavated from the Upper Cretaceous, Eagle Ford Formation for a
      sanitary landfill near Dallas, Texas spontaneously combusted. The shale is dark
      gray in color, with 3-4% fractional organic carbon, and no lignite seams. Gradual
      sifting and segregation of fine particles, having high surface area per unit
      volume, along with moisture trapped in the pile as it accumulated led to
      spontaneous combustion. Hot summer temperatures compounded the problem by heating
      the pile and preventing heat from efficiently venting to the atmosphere. Maximum
      temperatures exceeded 960 degrees F (516 degrees C) at several hot spots located
      approximately 4 m beneath the pile surface. The ongoing combustion problem, which
      has lasted for approximately 1 year, eventually will be extinguished by spreading
      the deposits in thin layers, and compacting them to reduce air circulation and
      segregation of fines.

PMID- 12214981
TI  - Isolation and partial characterization of CD36 from skim milk.
AB  - CD36, a common milk fat globule membrane glycoprotein, was isolated from skim
      milk by methods similar to those previously utilized for the isolation of
      sulfhydryl oxidase. Two separate methods that were employed, gave similar purity
      as observed by electrophoresis. The first was based on differential
      centrifugation and size-exclusion chromatography, whereas the second combined
      ultrafiltration and affinity chromatography. After significant purification, the
      protein was identified by Western blotting and sequence analysis. Deglycosylation
      decreased the apparent molecular mass from approximately 85 to 57 kDa. These
      results suggested tissue-specific glycosylation. The purified fractions also
      exhibited low levels of sulfhydryl oxidase activity, the significance of which
      will require further study.

PMID- 12214982
TI  - Germicidal activities of representatives of five different teat dip classes
      against three bovine mycoplasma species using a modified excised teat model.
AB  - Six representative teat dips from five different teat dip classes were tested for
      germicidal activity against challenge exposure to Mycoplasma bovis, Mycoplasma
      californicum, and Mycoplasma bovigenitalium using a modified excised teat model.
      All teat dip formulations tested were efficacious against all of the Mycoplasma
      species, providing bacterial logarithmic reductions above 4. The germicides
      performed best against M. bovigenitalium with an average log reduction (LR) of
      6.29. Average LR were 5.41 and 5.70 against M. bovis and M. californicum,
      respectively. The iodine and chlorhexidine products performed best against M.
      bovis and M. californicum, respectively, with complete kill of all organisms. The
      chlorhexidine and the barrier chlorine product also had complete kill of M.
      bovigenitalium organisms.

PMID- 12214983
TI  - Antimicrobial susceptibility of coagulase-negative staphylococci isolated from
      bovine mastitis in Argentina.
AB  - A total of 123 isolates of coagulase-negative staphylococci isolated from bovine
      clinical and subclinical mastitis in Argentina from March 1998 to March 2000 was
      investigated for in vitro susceptibility to several antimicrobial agents. Minimum
      inhibitory concentrations that inhibit 90% of the isolates tested (reported in
      micrograms per milliliter) were: 4.40, 0.38, 4.00, 0.75, 0.75, 3.60, and 2.00 for
      penicillin, oxacillin, cephalothin, gentamicin, erythromycin, clindamycin, and
      ampicillin-sulbactam, respectively. Resistance was detected in 34 (27.6%), 4
      (3.2%), 7 (5.7%), and 6 (4.8%) isolates for penicillin, oxacillin, erythromycin,
      and pirlimycin, respectively. No resistance was detected for gentamicin,
      cephalothin, or ampicillin-sulbactam. Results indicated that coagulase-negative
      staphylococci isolates in Argentina exhibited the highest degree of resistance to
      penicillin of all antimicrobial agents tested.

PMID- 12214984
TI  - Scanning the future--ultrasonography as a reproductive management tool for dairy
      cattle.
AB  - Application of transrectal real-time ultrasonography as a research tool to study
      bovine reproduction represents a technological breakthrough that has
      revolutionized our understanding of reproductive biology in cattle. The
      widespread adoption and use of ultrasonography for routine reproductive
      examinations of dairy cattle by bovine practitioners is the next contribution
      this technology will make to the dairy industry. Assessment of pregnancy status
      and fetal viability early postbreeding to identify cows that fail to conceive
      improves reproductive efficiency by decreasing the interval between artificial
      insemination services and increasing artificial insemination service rate. Early
      identification of cows carrying twin fetuses will allow for implementation of
      differential management strategies to abrogate negative effects of twinning
      during the periparturient period once such strategies have been developed.
      Ovarian and uterine pathologies not accurately detected via rectal palpation can
      easily be visualized by ultrasound, and appropriate therapies can be implemented.
      Determination of fetal sex in utero is useful when coupled with a management
      decision that justifies the expense of fetal sexing. Development of integrated
      reproductive management systems that combine ultrasound with new and existing
      reproductive technologies will further enhance the practical applications of
      ultrasonography. Development of Extension education programs to train bovine
      practitioners to use ultrasound for routine reproductive examinations is a
      critical step toward rapid implementation of this technology into the dairy
      industry.

PMID- 12214985
TI  - Metabolic and endocrine changes in response to endotoxin administration with or
      without oral arginine supplementation.
AB  - This study was performed to investigate blood metabolite, tumor necrosis factor
      alpha, and hormone responses to intravenous administration of lipopolysaccharides
      (2 microg of endotoxin of Escherichia coli 026:B6/kg body weight at times of
      feeding) in veal calves orally supplemented with arginine (0.25 g/kg of body
      weight twice daily for 4 d; group GrA) compared with calves not supplemented with
      arginine (group GrC). Arginine supplementation alone caused a significant rise of
      plasma arginine, urea, and insulin concentrations, whereas glucagon
      concentrations tended to increase, but there were no significant group
      differences. Concentrations of triglycerides, NEFA, glucose, protein, albumin,
      growth hormone, insulin-like growth factor-I, 3.5.3'-triiodothyronine, and
      thyroxine were not affected by arginine supplementation. Lipopolysaccharide
      administration alone caused a rise of tumor necrosis-factor-a, lactate, and
      cortisol concentrations and concentrations of tumor necrosis-factor-a after 1 h,
      and of triglycerides and urea after 6 h were higher, whereas of glucose after 3 h
      were lower in GrA than in GrC. Concentrations of NEFA, glucose, protein, albumin,
      insulin, growth hormone, insulin-like growth factor-I, 3.5.3'-triiodothyronine,
      and thyroxine were not affected by lipopolysaccharide administration. In
      conclusion, arginine supplementation had selective effects on plasma metabolites
      and hormones, but barely modified lipopolysaccharide effects. Effects of
      lipopolysaccharides in the postprandial state were different from what is usually
      seen in the fasted state.

PMID- 12214986
TI  - Effects of forage particle size and grain fermentability in midlactation cows. I.
      Milk production and diet digestibility.
AB  - Our study investigated the effects of, and interactions between, level of dietary
      ruminally fermentable carbohydrate (RFC) and forage particle size on milk
      production, nutrient digestibility, and microbial protein yield for dairy cows
      fed one level of dietary NDF. Eight cows (61 days in milk) were assigned to four
      treatments in a double 4 x 4 Latin square. Treatments were arranged in a 2 x 2
      factorial design; finely chopped alfalfa silage (FS) and coarse alfalfa silage
      (CS) were combined with concentrates based on either dry cracked shelled corn
      (DC; low RFC) or ground high-moisture corn (HMC; high RFC). Diets were fed ad
      libitum as a total mixed rations with a concentrate to forage ratio of 61:39.
      Diets based on DC had a predicted NEL content of 1.73 Mcallkg dry matter (DM),
      while HMC diets contained 1.80 Mcal/kg DM. Diets averaged 18.7% CP, 24.0% NDF,
      18.3% ADF, and 27.4% starch on a DM basis. Mean particle size of the four diets
      was 6.3, 2.8, 6.0, and 3.0 mm for DCCS, DCFS, HMCCS, and HMCFS, respectively.
      Increasing level of RFC decreased dry matter intake (DMI) from 25.0 to 23.8 kg/ d
      and organic matter intake from 22.3 to 21.1 kg/d, but intake was not affected by
      particle size. Milk production averaged 44.0 and 26.8 kg/d solids corrected milk
      (SCM) and was not affected by diet, but increasing level of RFC tended to
      increase milk yield. Efficiency of milk production, expressed as SCM/DMI,
      increased from 1.06 to 1.14 when level of RFC was increased. Milk composition or
      yield of milk components was not affected by diet, and averaged 3.53% fat, 3.11%
      protein, 1.55 kg/d fat, and 1.36 kg/d protein. Total tract digestibility of DM
      and OM increased from 71.4 to 73.0% and 72.4 to 76.1% for DM and OM,
      respectively, when level of RFC was increased. Total tract digestibility of fiber
      was unaffected by diet, but total tract starch digestibility increased from 93.1
      to 97.4% when HMC replaced DC. Total urinary excretion of the purine derivatives
      uric acid and allantoin increased from 415 to 472 mmol/d when level of RFC was
      increased, and calculated microbial N supply increased from 315 to 365 g/d. When
      expressed as per kilogram of digestible OMI, increasing level of RFC tended to
      increase microbial N supply (20.4 vs. 22.2 g/kg). Cow productivity was not
      affected by forage particle size and ruminally fermentable carbohydrates in this
      study.

PMID- 12214987
TI  - Effects of forage particle size and grain fermentability in midlactation cows.
      II. Ruminal pH and chewing activity.
AB  - Our study investigated the effects of, and interactions between, level of dietary
      ruminally fermentable carbohydrate (RFC) and forage particle size on rumen pH and
      chewing activity for dairy cows fed one level of dietary NDF. Also, correlations
      between intake, production, chewing, and ruminal pH parameters were investigated.
      Eight cows (61 days in milk) were assigned to four treatments in a double 4 x 4
      Latin square. Treatments were arranged in a 2 x 2 factorial design; finely
      chopped alfalfa silage (FS) and coarse alfalfa silage (CS) were combined with
      concentrates based on either dry, cracked-shelled corn (DC; low RFC) or ground,
      high-moisture corn (HMC; high RFC). Diets were fed ad libitum as a total mixed
      rations with a concentrate:forage ratio of 60:40. Diets averaged 18.7% crude
      protein, 24.0% neutral detergent fiber, 18.3% , acid detergent fiber and 27.4%
      starch on a DM basis. Mean particle size of the four diets were 6.3, 2.8, 6.0,
      and 3.0 mm for DCCS, DCFS, HMCCS, and HMCFS, respectively. Decreasing forage
      particle size decreased ruminal pH from 6.02 to 5.81, and increasing level of RFC
      decreased pH from 5.99 to 5.85. Minimum daily ruminal pH decreased from 5.66 to
      5.47 when level of RFC was increased, and decreased from 5.65 to 5.48 when forage
      particle size decreased. Time below pH 5.8 per day increased from 7.4 h to 10.8 h
      when level of RFC increased, and increased from 6.4 h to 11.8 h when forage
      particle size was decreased. Area below 5.8 showed the same relationship with RFC
      and forage particle size. Also, forage particle size affected the postprandial pH
      pattern. Cows spent more time eating when fed CS compared with FS (274 vs. 237
      min/d), and time spent eating decreased when level of RFC was increased (271 vs.
      241 min/d). Decreasing forage particle size decreased time spent ruminating (485
      vs. 320 min/d), rumination periods (15.3 vs. 11.7), and duration of rumination
      periods (29 vs. 26 min). Increasing level of RFC increased time spent ruminating
      per kg NDF intake (68.5 vs. 79.5 min/kg). Milk fat percentage was correlated to
      mean ruminal pH (r = 0.41), time spent below pH 5.8 (r = -0.55), and area below
      5.8 (r = -0.57), but not to intake or chewing variables. DMI of particles
      retained on a screen equivalent in size to the top screen of the Penn State
      particle separator was the intake parameter explaining most of the variation in
      mean ruminal pH (r = 0.27) and was correlated to time spent ruminating (r = 0.61)
      and chewing (r = 0.61).

PMID- 12214988
TI  - Effects of particle size of alfalfa-based dairy cow diets on site and extent of
      digestion.
AB  - Effects of ratio of alfalfa silage to alfalfa hay and forage particle size on
      nutrient intakes, site of digestion, rumen pools, and passage rate of ruminal
      contents were evaluated in a 4 x 4 Latin square design with a 2 x 2 factorial
      arrangement of treatments. The diets consisted of 60% barley-based concentrate
      and 40% forage made up either of 50:50 or 25:75 of alfalfa silage:alfalfa hay and
      alfalfa hay was either chopped or ground. Lactating dairy cows surgically fitted
      with ruminal and duodenal cannulas were used and offered ad libitum access to a
      total mixed ration. Intakes of nutrients were increased by increasing ratio of
      silage to hay but were not affected by particle size of forage. Change in ratio
      of silage to hay of diets did not affect site and extent of digestion. However,
      increased forage particle size of the diets improved digestibility of fiber and N
      in the total tract, and as well as digestibility of organic matter, starch, and
      acid detergent fiber in the intestine. There was a shift of starch digestion from
      the rumen to the intestine when forage particle size was increased, although
      total digestion of starch was not changed. Ruminal microbial protein synthesis
      and microbial efficiency also improved with increasing forage particle size. Cows
      fed ground hay versus chopped hay had significantly lower rumen wet mass
      regardless of the ratio of silage to hay. Reduced forage particle size also
      lowered ruminal nutrient pool size for cows fed the high silage diet. Ruminal
      passage rates of liquid and solid were decreased by reducing the ratio of silage
      to hay, and retention time of solids in the total tract was shortened by reducing
      forage particle size. These results indicate that manipulating ratio of silage to
      hay in the diets of dairy cows changed feed intake but had little effect on
      digestion. In contrast, increased forage particle size in dairy cow diets
      improved fiber digestion and microbial protein synthesis in the rumen, and
      shifted starch digestion from the rumen to the intestine. Dietary particle size,
      expressed as physically effective neutral detergent fiber, was a reliable
      indication of ruminal microbial protein synthesis and nutrient digestion.

PMID- 12214989
TI  - The effect of delayed ensiling and application of a propionic acid-based additive
      on the fermentation of barley silage.
AB  - Prolonged exposure to air can adversely affect the silage fermentation process.
      To investigate a possible method to overcome this problem, we determined if a
      buffered propionic acid-based additive, applied to chopped, whole-plant barley
      exposed to air before ensiling, would affect the subsequent fermentation. Wilted
      forage was chopped and treated with nothing, or with 0.1% (wt/wt wet forage) of a
      buffered propionic acid-based additive and ensiled immediately in quadruplicate
      20-L laboratory silos. Portions of the chopped forage, untreated and treated,
      were left in loose piles in a barn for 24 h before ensiling. Another portion of
      the untreated silage exposed to air for 24 h was also treated with 0.1% of the
      additive just before ensiling. Prolonged exposure to air before ensiling
      increased the numbers of yeasts on forages by more than 1,000-fold. The
      concentrations of water-soluble carbohydrates decreased by more than 50%; the
      ammonia-N concentrations increased 40%, and pH increased by more than 1 unit as a
      result of exposure to air. These changes were less in forage that was treated
      with the additive at chopping. After 60 d, silages of forages that were exposed
      to air before ensiling had a higher pH, higher concentrations of ammonia-N and
      butyric acid, and lower concentrations of lactic and acetic acids than silages of
      forage that had been ensiled immediately after harvest. In situ DM digestibility
      was lowest in untreated silages that had been exposed to air before ensiling. In
      contrast, treatment with the additive, applied before or after exposure to air,
      prevented the reduction in in vitro digestion.

PMID- 12214991
TI  - Whole linted cottonseed as a forage substitute: fiber effectiveness and digestion
      kinetics.
AB  - Six ruminally and duodenally cannulated Holstein cows were used in a 6 x 6 Latin
      square design to 1) evaluate the potential interaction in effectiveness of
      neutral detergent fiber (NDF) from whole cottonseed (WCS) when it was substituted
      for forage NDF (FNDF) and fed with ground (G) or steam-flaked (SF) corn and 2) to
      determine whether the kinetic properties of NDF digestion further clarify the
      effectiveness of WCS. The six dietary treatments were: forage control with G corn
      (21% FNDF), 5% WCS with G or SF corn (18% FNDF), 10% WCS with G or SF corn (15%
      FNDF), and 15% WCS with G corn (12% FNDF). Based on chewing activity, the NDF
      from WCS was estimated to be 84% (SE = 36%) as effective as alfalfa silage NDF.
      Decreasing passage and digestion rates of potentially digestible NDF with
      increasing WCS increased the evacuated pool size of ruminal DM, apparently
      explaining the similar ruminal mat consistency among treatments. Measures of
      effectiveness ofWCS treatments did not interact with corn source. Fluid dilution
      rate was estimated based on a two-compartment model describing Co dilution, but
      no treatment differences were detected. There was a strong linear bias for
      estimates of ruminal NDF digestibility based on a single compartment model using
      the digestion rate of potentially digestible NDF and the passage rate of either
      indigestible NDF or digestible NDF when compared with NDF digestibility
      calculated using duodenal flows. Although further verification is needed, these
      digestion and passage kinetics help explain why WCS are effective at stimulating
      chewing during eating and rumination.

PMID- 12214990
TI  - Whole linted cottonseed as a forage substitute fed with ground or steam-flaked
      corn: digestibility and performance.
AB  - Six ruminally and duodenally cannulated Holstein cows were used in a 6 x 6 Latin
      square design. The objective was to evaluate any potential interactions in site
      of nutrient digestion when neutral detergent fiber (NDF) from cottonseed was
      incrementally substituted for forage NDF (FNDF) from alfalfa silage and when
      starch availability was varied by feeding ground (G) or steam-flaked (SF) corn.
      Iso-NDF diets were forage control with G corn (21% FNDF), 5% whole cottonseed
      (WCS) with G or SF corn (18% FNDF), 10% WCS with G or SF corn (15% FNDF), and 15%
      WCS with G corn (12% FNDF). Ruminal or total tract digestibilities of organic
      matter (OM) or nonstructural carbohydrate (NSC) were unaffected, but efficiency
      of microbial protein synthesis decreased as WCS increased. Ruminal NDF
      digestibility was not affected despite a linear decrease in pH, but postruminal
      NDF digestibility decreased with increasing WCS. Ruminal digestibilities of OM
      and NSC were higher for SF than G corn but did not affect efficiency of microbial
      N synthesis. Dry matter intake increased quadratically with increasing level of
      WCS but decreased when SF replaced G corn. Milk yield did not differ across
      treatments. Milk fat percentage was affected quadratically and milk protein
      increased linearly with increasing WCS. Milk fat percentage decreased but milk
      protein was not affected when SF replaced G corn. Lack of an interaction between
      corn source and level of WCS substitution suggests that WCS was equally effective
      in maintaining ruminal fermentation and digestibility in diets varying in ruminal
      starch availability.

PMID- 12214992
TI  - Impact of feeding a raw soybean hull-condensed corn steep liquor pellet on
      induced subacute ruminal acidosis in lactating cows.
AB  - We used four ruminally cannulated, multiparous Holstein cows (690 kg; 21 kg/d
      milk) in a 2-period crossover design to determine the impact of feeding a raw
      soybean hull-corn steep liquor pellet (SHSL) on induced subacute ruminal acidosis
      (SARA) in lactating cows. Cows were fed control [30% alfalfa hay, 15% corn
      silage, 34% corn, 9% whole cottonseed, 5% soybean meal (SBM)] or SHSL (20% of
      diet DM) diets as TMR. SHSL replaced 6.2% alfalfa hay, 3.7% corn silage, 6.6%
      corn, and 3.3% SBM. Periods were 15 d (10 d adaptation, 2 d for prechallenge
      measures, and 3 d of SARA challenge). Cows were fed once daily at a common DMI
      dictated by the cow consuming the least. Cows were fasted 12 h before the first
      SARA challenge. For each of the three SARA challenges, cows were offered 75% of
      their daily diet at 0600 h. The remaining 25% of diet DM was replaced by ground
      corn, which was mixed with the orts that remained 2 h after feeding and placed
      into the rumen. Ruminal pH declined linearly with time after feeding, and this
      decrease was greater during the SARA challenges. Ruminal lactate increased
      linearly with repeated SARA challenges. Concentrations of total ruminal VFA
      increased linearly after feeding, and increases were greater when cows were
      challenged. No differences were observed due to SHSL inclusion. The model induced
      SARA, but partial replacement of alfalfa, corn silage, corn, and SBM by SHSL did
      not influence responses to SARA challenges.

PMID- 12214993
TI  - Influence of yeast culture on ruminal microbial metabolism in continuous culture.
AB  - A continuous culture study was conducted to evaluate the effect of two different
      yeast cultures on ruminal microbial metabolism. The treatments were a) control
      lactation ration, b) yeast culture 1 (YC1, Diamond-V XP) and c) yeast culture 2
      (YC2, A-Max), both fed at an equivalent of 57 g/head per day. The results showed
      that both yeast culture products increased dry matter (DM) digestion, propionic
      acid production, and protein digestion compared with the control. Yeast culture 1
      demonstrated an increase in molar percentage of propionic acid, a reduction in
      acetic acid, and a lower mean nadir (daily low) pH compared with YC2. Ruminal
      cultures treated with YC digested more protein and contributed less bypass N than
      control. Supplementing YC2 resulted in a tendency for higher microbial N/kg DM
      digestion than YC1. Yeast culture 1 resulted in production of rumen microbes
      containing less protein and more ash than YC2. These results support previous
      research findings that yeast culture does influence microbial metabolism, and
      specific yeast cultures may have different modes of action.

PMID- 12214994
TI  - Stimulatory and inhibitory effects of protein amino acids on growth rate and
      efficiency of mixed ruminal bacteria.
AB  - Mixed ruminal bacteria were incubated in vitro with glucose, xylose, cellobiose,
      and various protein amino acids replaced isonitrogenously with 25% (i.e., 25 mg
      of N/L) of ammonia-N, to determine the growth rate and the amount of sugar
      consumed in the exponential growth phase. The growth rate and efficiency (grams
      of bacteria per gram of sugars) increased by 46 and 15%, respectively, when a
      mixture of 20 amino acids was added. On the other hand, neither growth rate nor
      efficiency increased when any one of these amino acids was added singly, except
      for Glu and Gln, each of which produced significant but small improvements. The
      stimulatory effect of the combined amino acids on bacterial growth declined when
      each of Leu, Trp, Tyr, Glu, Met, Phe, and Val was removed from the original group
      of 20. When a mixture of only these seven amino acids was used as a supplement,
      their stimulatory effects on growth rate and efficiency were only 21 and 25%,
      respectively, of the effects that the mixture of 20 amino acids showed. The
      effects increased to 76 and 72% on growth rate and efficiency, respectively, when
      Gly, Cys, and His were supplied in addition to the seven amino acids. The growth
      rate and efficiency of the ruminal bacteria were inhibited by an addition of each
      of Ile, Thr, Cys, Phe, Leu, Lys, or Val to ammonia-N, and the effects of the
      first five of these amino acids were highly significant. Isoleucine, threonine,
      and phenylalanine were each inhibitory even at a low concentration (1 mg of NL),
      while cysteine and leucine showed inhibitory effects at higher concentrations
      (more than 10 mg of N/L). A higher growth rate of the ruminal bacteria when
      supplemented with amino acid mixtures was accompanied with a higher growth
      efficiency, which was attributable to a relatively smaller proportion of energy
      expended on maintenance according to the Pirt derivation.

PMID- 12214995
TI  - Effect of dose of calcium salts of conjugated linoleic acid (CLA) on percentage
      and fatty acid content of milk fat in midlactation holstein cows.
AB  - Increasing conjugated linoleic acid (CLA) content of milk fat from lactating
      dairy cattle has become a research interest due to the possible health benefits
      afforded humans consuming CLA. Dietary supplementation of CLA to lactating dairy
      cows is one potential method by which CLA content of milk and dairy products may
      be enhanced. Feeding CLA in calcium salt form could potentially deliver CLA to
      the lower digestive tract through prevention of biohydrogenation by rumen
      microbes. Milk fat depression (MFD) occurs when cows receive CLA-60, a
      commercially available CLA source containing numerous CLA isomers, abomasally.
      Our objectives were to determine the quantity of CLA as calcium salts required to
      elicit maximal MFD and to evaluate the effects of CLA supplementation on fatty
      acid composition of milk fat. Five Holstein cows at approximately 93 DIM were
      utilized in a 5 x 5 balanced Latin square crossover design. Periods were 14-d in
      length with a 5-d treatment phase and 9-d rest phase. Treatments were 5-d
      supplementation of 0, 12.5, 25, 50, and 100 g of CLA-60 in calcium salt form.
      Milk samples were collected on d 5 of CLA supplementation and analyzed for
      composition and fatty acid profile. Regression analysis of milk fat data
      suggested that MFD was not maximized over the dose levels investigated, despite
      delivery of 34.5 g of trans-10, cis-12 CLA in the 100-g dose of CLA.
      Supplementation with 50 and 100 g of CLA per day resulted in a reduction of milk
      fat percent of 29 and 34%, respectively. Trend analysis indicated a linear
      decrease in the milk fat content of caprylic, capric, and lauric acids as the
      dose of CLA increased. Milk fat content of cis-9, trans-11, and trans-10, cis-12
      CLA increased at an increasing rate as dose increased.

PMID- 12214996
TI  - Genetic parameters for level and change of body condition score and body weight
      in dairy cows.
AB  - (Co)variance components for body condition score (BCS), body weight (BW), BCS
      change, BW change, and milk yield traits were estimated. The data analyzed
      included 6646 multiparous Holstein-Friesian cows with records for BCS, BW,
      and(or) milk yield at different stages of lactation from 74 dairy herds
      throughout Southern Ireland. Heritability estimates for BCS ranged from 0.27 to
      0.37, while those for BCS change ranged from 0.02 to 0.10. Heritability estimates
      for BW records varied from 0.39 to 0.50, while heritabilities for BW change were
      similar to those observed for BCS change (0.03 to 0.09). The genetic correlations
      between BCS and BW at the same days in milk deviated little from 0.50, and the
      genetic correlations between BCS change and BW change over the same period ranged
      from 0.42 to 0.55. BCS and BW directly postpartum were both phenotypically and
      genetically negatively correlated with both BW change and BCS change in early
      lactation. The genetic correlations between BCS and milk yield were negative. The
      results of the present study show that animals that lose most BCS in early
      lactation tend to gain most BCS in late lactation, a trend also exhibited by BW.

PMID- 12214997
TI  - An autoregressive repeatability animal model for test-day records in multiple
      lactations.
AB  - Test-day (TD) models are becoming a standard for genetic evaluation of production
      traits in dairy cattle. Various approaches to model covariances between TD
      records include random regression, autoregressive repeatability, orthogonal
      polynomials, and models based on character processing. The applicability of these
      models is mainly associated with the number of parameters to estimate,
      incorporation of multiple lactations, and the accuracy of correlations generated
      by the cow's repeated expression of milking performance (TD yields) within and
      across lactations. We define and evaluate a multiple-lactation, autoregressive
      repeatability model that disentangles environmental effects due to cow within and
      between lactations. Simulated records either included or ignored a long-term
      environmental effect between lactations. Our autoregressive TD animal model
      correctly detected presence and the absence of this effect and accurately
      recovered the assumed variance components and correlations underlying the data
      (10 parameters for three lactations). Estimates of variance components and
      autocorrelation coefficients were obtained using DFREML-simplex methodology.
      Given the value of this approach to reduce the size of residual variance
      components, autoregressive animal models are a preferable alternative to
      classical methods based on cumulative lactation yield to improve milk production
      in dairy cattle.

PMID- 12214998
TI  - Relationship between DHI production values and Myers-Briggs type indicator as a
      measure of management ability.
AB  - Associations between owners' Myers-Briggs Type Indicator (MBTI) preferences (E =
      extraversion vs. I = introversion; S = sensing vs. N = intuition; T = thinking vs
      F = feeling; J = judging vs. P = perceiving) and 21 Dairy Herd Improvement (DHI)
      production variables were determined on 60 farms. Of 60 dairy farmers
      participating, 51 were from Holstein farms (85%) and nine from farms with other
      breeds, primarily Jersey. Cows were milked either twice (n = 44 herds, 73%) or
      three times (n = 16) per day. Farmers were evenly split between the "E" and "I"
      dimension, whereas 93% of the farmers were "S," 75% "T," and 62% "J.".
      Individuals with a preference for the "I" dimension were associated with higher
      peak and mature equivalent milk yield than those individuals with a preference
      for the "E" dimension. The "T" and "J" dimensions had a significantly higher
      percentage of the herd with records usable by USDA and a lower percentage of
      animals pregnant by the goal set by the dairy producer than the "F" and "P"
      dimensions. Herds managed by individuals with a combination preference of "E" and
      "P" produced 7 to 10 kg of 3.5% FCM/cow per day less or 1,820 to 2,752 kg/ cow
      RHA ECM less than other combinations of the "E-I" and "J-P" dimensions. Those
      herds also had longer days dry and a lower percentage of records usable by USDA,
      suggesting that the "E-P" preference is less favorably associated to those
      measures of herd performance. The MBTI had limited association with many DHI
      production variables, but relationships to measures of labor and business
      management should be examined.

PMID- 12214999
TI  - Managerial and financial implications of major dairy farm expansions in Michigan
      and Wisconsin.
AB  - This study examines the experiences and results of major dairy farm expansions in
      Michigan and Wisconsin. Twenty dairy farms that had one-time herd size increases
      of at least 20% between 1988 and 1998 were selected, surveyed, interviewed, and
      analyzed. A case study format reveals individual experiences and problem
      solutions. On average, studied dairy farms increased herd size from 296 to 569
      cows. The most commonly cited reason for expansion was increased profits. On
      average, net farm income and return to operator management and capital improved
      following expansion. The most profitable expansions were highly correlated with
      modernizing facilities. In addition, a decline in return on assets was, in
      several cases, due to taking on too many new partners relative to the increase in
      herd size. Dairy farms were able to increase milk production and experienced a
      significant decrease in labor and management expense per hundredweight of milk
      produced through expansion. Outsourcing and the use of consultants increased with
      expansion. Public relations problems were not substantial impediments for
      producers who took a proactive approach. Reflecting on the expansion experience,
      managers indicated that human resource, financial, operations, herd management,
      and strategic management skills were the most important skills to achieve a
      successful expansion.

PMID- 12215000
TI  - Functional impairment and the economic consequences of female breast cancer.
AB  - Recent trends in breast cancer diagnosis and mortality suggest that long-term
      survivors are now more likely to be functionally impaired and, hence, more likely
      to experience adverse economic outcomes. This study tests whether women who have
      survived breast cancer for at least five years exhibit more, or more severe,
      functional impairments than otherwise similar women without breast cancer. It
      also tests whether women with more severe impairments experience poorer economic
      outcomes attributable to their functional status. A group of 105 breast cancer
      survivors was interviewed to obtain data on health and economic changes in the
      five-year period since diagnosis and initial treatment. An age- and work-matched
      group of 105 women without cancer was also interviewed to obtain the same data
      over the same time period. Key changes in the functional status of the subjects
      as well as economic outcomes such as changes in market earnings, household
      income, and insurance coverage were measured. Whether impairment is more severe
      in the breast cancer group than the comparison group was then tested
      statistically; whether economic outcomes are more adverse in more impaired than
      less impaired women regardless of their breast cancer status was also tested. The
      analysis turned up statistically significant evidence in regard to each of these
      relationships. Breast cancer survivors were more likely than controls to be
      functionally impaired at the five-year benchmark. Impaired women, in turn, were
      more likely to reduce work effort and experience downturns in market earnings,
      among other things. Policy and research implications are discussed.

PMID- 12215001
TI  - Pap smear use in a population of older Mexican-American women.
AB  - BACKGROUND: Hispanic women and older women (age > or = 50 years) in general have
      been identified as populations of women who often underutilize Papanicolaou (Pap)
      smears. OBJECTIVE: To report the rates of cervical cancer screening in a group of
      older Mexican American women and to identify the correlates of having a Pap smear
      in the past three years. DATA SOURCE: The Mammography Use by Older Mexican
      American Women Survey, a stratified area probability sample of 452 women ages 50
      74 from three southeast Texas counties. Self-report data was collected with in
      person interviews from 1997 to 1999. RESULTS: We found that 93.1% of the women
      reported at least one Pap smear in their lifetime and that 64.1% reported a Pap
      smear in the past three years. Odds of reporting a recent Pap smear was lower for
      older women (OR 0.51, 95% CI 0.32-0.82) and those below the poverty line (OR
      0.52, 95% CI 0.33-0.82). The odds were higher for women who had a regular doctor
      for female care (OR 6.49, 95% CI 2.96-14.23) or a regular clinic or hospital
      source for female care (OR 5.50, 95% CI 2.55-11.89). Among these older Mexican
      American women, cultural factors (language of interview, acculturation, fatalism)
      did not have a significant effect on screening use. CONCLUSION: Recent Pap smear
      use (64.1%) falls well below the year 2010 goal of 90%. Efforts need to be made
      to overcome barriers to Pap smear utilization for these women, such as providing
      access to female medical care.

PMID- 12215002
TI  - Using the internet to identify women's sources of breast health education and
      screening.
AB  - Health professionals, women's groups, the media and the Internet have all played
      a role in educating the public about breast health and breast screening methods.
      Yet, with all the information that is available to women, their participation
      rates have been less than optimal. This paradox has resulted in the need to learn
      more about the sources that influence women to participate in breast screening.
      In an innovative study using the Internet, over 800 women, primarily from Canada
      and the United States, were surveyed about their knowledge, attitudes and
      influences regarding their breast screening practices. Current health status,
      screening practices and influences of various health professionals on women's
      health promotion activities were analyzed. Comparisons of the women's perceptions
      across age groups and national differences between Canadian and American
      respondents are presented. Women in the older age group reported receiving more
      encouragement for breast screening activities from physicians, nurses and others
      than did younger women. American respondents reported perceiving more support
      from nurses for breast screening than did their Canadian counterparts. A high
      number of American respondents reported having been diagnosed with breast cancer,
      while only a small number of Canadian respondents reported this diagnosis. The
      results from this study can be used in planning health promotion activities
      relevant to various populations of women. Benefits and limitations of using the
      Internet as a research medium are briefly discussed.

PMID- 12215003
TI  - Role occupancy, role quality, and psychological distress in Chinese women.
AB  - This study explored the associations between role occupancy, role quality, and
      psychological distress in 897 Chinese women in Hong Kong. Results showed that
      employed as compared to nonemployed women reported a lower level of psychological
      distress. Never married as compared to married women, and mothers as compared to
      childless women, did not differ in their levels of psychological symptoms.
      Correlation results indicated that a net gain of rewards over concerns about
      social roles was negatively related to psychological distress. The number of
      social roles was related to the balance between rewards and concerns between
      social roles, but had no significant association with mental health status of
      women. Results of the hierarchical regression analyses showed that good mother
      role quality and the occupancy of the paid worker role were significant
      predictors of a low level of psychological distress. Findings based on a
      subsample of employed mothers failed to support the compensatory and spillover
      hypotheses. Limitations and implications for future studies were discussed.

PMID- 12215004
TI  - Physical activity among older Filipino-American women.
AB  - Filipino women (N = 530, mean age 63 years, predominantly low income) were
      recruited through various community based organizations and churches in Los
      Angeles County. All women were randomly invited to attend a single group session
      with a Filipino health educator to discuss breast and cervical cancer screening
      or the health benefits of exercise. At 3 months after the group session, the
      exercise assessment tool used in the National Health and Nutrition Examination
      Survey III was completed by 487 women (92 percent retention rate). This paper
      describes the pattern of physical activity among older Filipino-American women
      and a physical activity intervention specifically designed for this group.

PMID- 12215005
TI  - Factors affecting reproductive decisions of African American women living with
      HIV.
AB  - PURPOSE: This exploratory study used focus groups to examine attitudes and
      beliefs of HIV-infected African American women of child-bearing age about
      pregnancy and antiretroviral therapy. METHODS: A convenience sample of thirty
      three African American women of child-bearing age participated in five focus
      groups. Attitudes and beliefs about pregnancy decisions and the use of
      antiretroviral therapy during pregnancy were examined. RESULTS: Many of the women
      in this study living with HIV remained committed to having children and expressed
      confusion about their chances of transmitting the virus to their children.
      CONCLUSIONS: Health care providers must be aware of these concerns and convey
      clear and accurate information through the most readily accepted channels.
      Participants suggested that messages about these issues be conveyed by other
      women living with HIV who have faced these same decisions.

PMID- 12215006
TI  - Factors associated with antiretroviral adherence among HIV-infected women with
      children.
AB  - HIV symptomatic or AIDS diagnosed women who had a young well child were recruited
      for a study investigating their adherence to antiretrovirals (N = 46). Very poor
      rates of adherence were found, ranging from 43% (pill count assessment) to 56%
      (self-report of 3-day adherence to dose). Several factors were associated with
      nonadherence, including alcohol use, perceived stress, having a partner and age
      of youngest child, poor self-efficacy to stay with treatment, and poor outcome
      expectancies regarding the benefits of following the treatment regimen.
      Interventions to assist these women in improving adherence are urgently needed.

PMID- 12215007
TI  - Wilms tumor gene (WT1) expression as a panleukemic marker.
AB  - The Wilms tumor gene (WT1) is expressed in blasts of patients with acute
      leukemia, irrespective of lineage, and WT1 nuclear protein is detectable in the
      majority of such blasts. Only very few physiologic hematopoietic progenitors
      express WT1, but the WT1 expression level of these progenitors and that of
      leukemic blasts are comparable. Although not specific for acute hematologic
      malignant diseases, continuous WT1 expression in almost all leukemic blasts
      strikingly contrasts to its rather transient expression in very few physiologic
      hematopoietic progenitors. Quantitative and semiquantitative WT1 reverse
      transcriptase polymerase chain reaction (RT-PCR) protocols have limitations in
      discriminating physiologic from pathologic overall WT1 expression levels in
      mononuclear cell preparations. Because of these limitations, reports conflict on
      the usefulness of long-term monitoring of WT1 expression in patients with acute
      leukemia. Real-time quantitative WT1 RT-PCR protocols, however, have been
      developed and tested in small series of patients with acute leukemia. Such
      protocols hold promise to enable evaluation of the individual treatment response
      (short-term monitoring) and early diagnosis of imminent relapse through the
      detection and long-term monitoring of minimal residual disease in patients with
      acute leukemia. These protocols also should facilitate the notoriously difficult
      distinction between eosinophilic leukemia and hypereosinophilic syndromes. Data
      on WT1 expression in leukemic blasts and their physiologic counterparts are
      discussed in light of clinical relevance.

PMID- 12215008
TI  - Regulation of gene expression by WT1 in development and tumorigenesis.
AB  - WT1 encodes a zinc finger transcription factor implicated in normal development
      and tumorigenesis. Germline mutation or deletion of WT1 results in a spectrum of
      abnormal kidney development, male-to-female intersex disorders, and
      predisposition to pediatric nephroblastoma, Wilms tumor. Initially thought to
      encode a transcriptional repressor, WT1-dependent functions are now more clearly
      linked to its property as a transcriptional activator of genes involved in renal
      development and sex determination. WT1 is expressed in 4 isoforms as a result of
      2 alternative messenger RNA splicing events, the more significant of which
      encodes the 3 amino acids lysine, threonine, and serine (KTS) between zinc
      fingers 3 and 4. Although WT1 isoforms lacking KTS act as sequence-specific DNA
      binding factors, a large body of evidence now implicates the KTS-containing
      isoforms in RNA processing. In keeping with distinct biochemical mechanisms for
      these isoforms, genetic data from humans and mice point to separate but partially
      overlapping roles for WT1 (+KTS) and (-KTS) during genitourinary development.
      Recently, a hematopoietic model system has been used to study functional
      properties of WT1 in vitro. WT1 expression in primary hematopoietic cells leads
      to stage-specific effects that may be relevant to WT1-mediated tumor suppression.

PMID- 12215009
TI  - The role of WT1 in oncogenesis: tumor suppressor or oncogene?
AB  - Although originally identified as a tumor suppressor gene, WT1 is overexpressed
      in a variety of hematologic malignancies and solid tumors, including acute
      leukemia, breast cancer, malignant mesothelioma, renal cell carcinoma, and
      others. Overexpression of both wild-type and mutant WT1 has been reported. In
      some cases, this finding represents overexpression of a gene that should be
      expressed at lower levels, but in other cases, WT1 is expressed at high levels in
      a tissue type in which there is normally no expression at all. In this review,
      the mechanisms of altered WT1 expression are explored, including changes in
      promoter methylation. WT1 target genes that may be important for oncogenesis are
      discussed, as is the use of WT1 expression as a diagnostic tool. The prognostic
      implications of altered WT1 expression and the potential for immunotherapy aimed
      at WT1 are also discussed.

PMID- 12215010
TI  - Cancer immunotherapy targeting WT1 protein.
AB  - The Wilms tumor gene WT1 is expressed in leukemias and various kinds of solid
      tumors, including lung and breast cancer, and exerts an oncogenic function in
      these malignancies, suggesting that WT1 protein is a novel, overexpressed tumor
      antigen. The WT1 protein, in fact, is an attractive tumor rejection antigen in
      animal models. Stimulation in vitro of peripheral blood mononuclear cells with
      HLA-A*2402--and HLA-A*0201--restricted 9-mer WT1 peptides elicits WT1-specific
      cytotoxic T-lymphocytes (CTLs), and the CTLs kill endogenously WT1-expressing
      leukemia or solid tumor cells. Furthermore, WT1 immunoglobulin M (IgM) and IgG
      antibodies are detected in patients with hematopoietic malignancies such as acute
      myeloid leukemia, chronic myeloid leukemia, and myelodysplastic syndromes,
      indicating that WT1 protein overexpressed by leukemia cells is indeed
      immunogenic. Taken together, these results demonstrate that WT1 protein is a
      promising tumor antigen for cancer immunotherapy against leukemias and various
      kinds of solid tumors, including lung and breast cancer.

PMID- 12215012
TI  - Hb Nishinomiya [Leu-Gly-inserted between codons 69(E13) and 70(E14) of beta]: a
      novel unstable hemoglobin with reduced oxygen affinity found in a patient with
      spherocytic hemolysis.
AB  - Substantially decreased oxygen saturation levels were incidentally detected by
      pulseoxymetry in a patient with spherocytic hemolysis who was undergoing
      laparoscopic splenectomy. Molecular analysis revealed that he was carrying
      hemoglobin (Hb) Nishinomiya, a novel Hb variant [Leu-Gly-inserted between codons
      69(E13) and 70(E14) of beta]. Amino acid substitutions around positions 70-73(E13
      17) of the beta chain are likely to change stability and oxygen affinity, as has
      been demonstrated in several Hb variants including Hb Seattle. The apparent
      substitution of the amino acid residues in the heme pocket of the beta chain
      explains the decreased stability and oxygen affinity of Hb Nishinomiya.

PMID- 12215013
TI  - Molecular heterogeneity of glucose-6-phosphate dehydrogenase deficiency in Malays
      in Malaysia.
AB  - Multiplex polymerase chain reaction (PCR) using multiple tandem forward primers
      and a common reverse primer (MPTP) was recently established as a comprehensive
      screening method for mutations in X-linked recessive diseases. In the work
      reported here, MPTP was used to scan for mutations of the glucose-6-phosphate
      dehydrogenase (G6PD) gene. Mutations in exons 3,4,5,6,7,9, 11, and 12 of the G6PD
      gene were screened by MPTP in 93 unrelated Malaysian patients with G6PD
      deficiency. Of the 93 patients, 80 (86%) had identified mutations. Although all
      of these were missense mutations, identified nucleotide changes were
      heterogeneous, with 9 mutations involving various parts of the exons. These 9
      mutations were G-to-A nucleotide changes at nucleotide 871 of the G6PD gene
      (G871A), corresponding to G6PD Viangchan, G6PD Mediterranean (C563T), G6PD Vanua
      Lava (T383C), G6PD Coimbra (C592T), G6PD Kaiping (G1388A), G6PD Orissa (C131G),
      G6PD Mahidol (G487A), G6PD Canton (G1376T), and G6PD Chatham (G1003A). Our
      results document heterogeneous mutations of the G6PD gene in the Malaysian
      population.

PMID- 12215014
TI  - Extramedullary hematopoiesis in hereditary spherocytosis deficient in ankyrin: a
      case report.
AB  - Hereditary spherocytosis (HS) is a common inherited hemolytic anemia due to red
      cell membrane defects. Extramedullary hematopoiesis is a compensatory response to
      insufficient bone marrow blood cell production. The preferred sites of
      extramedullary hematopoietic involvement are the spleen, liver, and lymph nodes,
      but in HS the posterior paravertebral mediastinum is also commonly involved. A
      nonsplenectomized 74-year-old man with mild HS, with primary deficiency in
      ankyrin, was found by magnetic resonance imaging to have thoracic paravertebral
      hematopoietic masses. The patient showed high serum levels of erythropoietin,
      which may have played a role in the development of extramedullary hematopoietic
      masses through a continuous hematopoietic stimulus to erythroid cells in the
      propositus. The long-standing history of respiratory infections and of hypoxia in
      the propositus may have been an additional etiological factor.

PMID- 12215011
TI  - Clinical and pathological criteria for the diagnosis of essential
      thrombocythemia, polycythemia vera, and idiopathic myelofibrosis (agnogenic
      myeloid metaplasia).
AB  - A set of clinical and pathological criteria for the diagnosis and staging of
      Philadelphia chromosome-negative myeloproliferative disorders (Ph(1-)-MPDs) is
      presented by including bone marrow histopathology as a significant tool to
      identify the early, manifest, and advanced stages of essential thrombocythemia
      (ET), polycythemia vera (PV), and idiopathic myelofibrosis/agnogenic myeloid
      metaplasia (IMF/AMM). This combined approach provides a pathognomonic clue to
      each of the different subtypes of Ph(1-)-MPDs and further enables recognition of
      the various steps in the evolution of the myeloproliferative process Increase and
      clustering of giant to large megakaryocytes with mature cytoplasm and
      multilobulated staghorn-like nuclei in a normal or only slightly increased
      cellular bone marrow represent major hallmarks of ET. Loose assemblies of small
      to giant pleiomorphic megakaryocytes containing deeply lobulated nuclei together
      with a proliferation of erythro- and granulopoiesis (panmyelosis) are the
      specific lesions of PV. The initial prefibrotic and the overt and more advanced
      myelofibrotic stages of IMF/AMM show a pronounced proliferation of an abnormal
      megakaryo- and granulopoiesis dominated by clustered atypical medium-sized to
      giant megakaryocytes with cloud-like, bulbous, and often hyperchromatic nuclei,
      which are not seen in allied subtypes of MPDs including chronic myeloid leukemia
      (Ph(1+)-CML) and myelodysplastic syndromes (MDS). The presented clinical and
      pathological criteria modify the Polycythemia Vera Study Group (PVSG) proposals
      for the Ph(1-)-MPDs by including bone marrow histopathology and are in keeping
      with features outlined in the new World Health Organization classification. The
      latter allows the differentiation of true ET from reactive thrombocytosis and
      from thrombocythemias as an eventually presenting finding in PV, IMF/AMM, MDS,
      and Ph(1+)-CML. Moreover, these diagnostic guidelines are able to separate latent
      and early PV from secondary erythrocytosis and to detect the prefibrotic and
      early stages of IMF/AMM. Myelofibrosis is not a feature of ET and is rarely
      observed in PV at time of diagnosis, but it becomes apparent during long-term
      follow-up and constitutes a prominent lesion during the course of IMF/ AMM. Life
      expectancy is almost normal in ET and is also not significantly altered during
      the first, but compromised during the second, decade of follow-up in PV. On the
      other hand, survival is substantially shortened in IMF/AMM, even for patients
      with thrombocythemia as a frequent finding of prefibrotic and early stage
      IMF/AMM.

PMID- 12215015
TI  - Severe immune dysfunction after lethal neutron irradiation in a JCO nuclear
      facility accident victim.
AB  - The optimal treatment for the hematological toxicity of acute radiation syndrome
      (ARS) is not fully established, especially in cases of high-dose nonuniform
      irradiation by mixed neutrons and gamma-rays, because estimation of the
      irradiation dose (dosimetry) and prediction of autologous hematological recovery
      are complicated. For the treatment of ARS, we performed HLA-DRB1-mismatched
      unrelated umbilical cord blood transplantation (CBT) for a nuclear accident
      victim who received 8 to 10 GyEq mixed neutron and gamma-ray irradiation at the
      JCO Co. Ltd. nuclear processing facility in Tokaimura, Japan. Donor/ recipient
      mixed chimerism was attained; thereafter rapid autologous hematopoietic recovery
      was achieved in concordance with the termination of immunosuppressants. Immune
      function examined in vitro showed recovery of the autologous immune system was
      severely impaired. Although the naive T-cell fraction and the helper T-cell
      subtype 1 fraction were increased, the mitogenic responses of T-cells and the
      allogeneic mixed leukocyte reaction were severely suppressed. Endogenous
      immunoglobulin production was also suppressed until 120 days after the accident.
      Although skin transplantation for ARS was successful, the patient died of
      infectious complications and subsequent acute respiratory distress syndrome 210
      days after the accident. These results suggest that fast neutrons in doses higher
      than 8 to 10 Gy cause complete abrogation of the human immune system, which may
      lead to fatal outcome even if autologous hematopoiesis recovers. The roles of
      transplantation, autologous hematopoietic recovery, chimerism, immune
      suppression, and immune function are discussed.

PMID- 12215017
TI  - Long-term survivors with adult acute leukemia in complete remission:
      complications and return to work.
AB  - For addressing, and eventually being able to predict and prevent, both disease
      related complications and changes in social status in long-term acute leukemia
      survivors, the follow-up is the most important factor after treatment. To this
      end, we assessed the complications following the attainment of complete remission
      in adult acute leukemia patients and the changes in social status of patients
      surviving more than 5 years after disease onset. In our study population of 42
      survivors, 24 (57.1%) suffered from various combinations of 18 types of
      identified complications including posttransfusion hepatitis, diabetes mellitus,
      and idiopathic osteonecrosis. Regarding fertility, 9 live births were recorded in
      this cohort, from 2 female patients and the partner of a male patient. Of these
      42 long-term survivors, at the time of this report 48.5% were working full- or
      part-time, 9.0% were unemployed, 30.3% were homemakers, and 12.2% were retired.

PMID- 12215016
TI  - Establishment of a primary effusion lymphoma cell line (RM-P1) and in vivo growth
      system using SCID mice.
AB  - Primary effusion lymphoma (PEL) is recognized as a unique lymphoma entity, which
      occurs exclusively in body cavities as a serous lymphomatous effusion without
      tumor formation or organ infiltration. We established a cell line of B-cell
      origin from a pericardial effusion of a 63-year-old Japanese PEL patient who did
      not have human immunodeficiency virus infection. This PEL cell line had human
      herpesvirus-8 (HHV-8) and Epstein-Barr virus (EBV) infection. We named this cell
      line RM-P1. This cell line showed complex chromosomal abnormalities that could
      not be identified by G-banding. However, spectral karyotyping analysis determined
      the origin and organization of all unidentified chromosomal abnormalities. When
      inoculated into the peritoneal cavity of 8 severe combined immunodeficiency
      (SCID) mice depleted of natural killer cells, RM-P1 cells induced solid tumor
      with ascites in all animals tested. These tumor and ascitic cells had the same
      immunogenotypic features as those of the original RM-P1. These 2 types of cells
      were positive for both HHV-8 and EBV as demonstrated using polymerase chain
      reaction. Fluorescence-activated cell sorting analyses showed that neither tumors
      nor ascitic cells grown in SCID mice expressed leukocyte function-associated
      antigen (LFA)-1alpha (CD11a), LFA-1lbeta (CD18), LFA-2 (CD2), LFA-3 (CD58),
      intercellular adhesion molecule (ICAM)-1 (CD54), ICAM-2 (CD102), ICAM-3 (CD50),
      or leukocyte endothelial adhesion molecule (LECAM)-1 (CD62L), suggesting that
      these cytoadhesion molecules are not involved in tumor formation of RM-P1 cells
      in vivo. The establishment of the RM-P1 cell line and the animal model of PEL may
      provide insights for understanding the relationship between these viruses and PEL
      and for understand the mechanism for PEL.

PMID- 12215018
TI  - Detection of the BCR-ABL gene by interphase fluorescence in situ hybridization
      (iFISH) in chronic myelogenous leukemia patients after hemopoietic stem cell
      transplantation: the feasibility of iFISH monitoring of therapeutic response in
      peripheral blood.
AB  - The detection of the Philadelphia (Ph) translocation has been accomplished
      primarily by cytogenetic analysis and reverse transcriptase polymerase chain
      reaction (RT-PCR). RT-PCR is highly sensitive (1/10(4)-10(6)) but not
      quantitatively reliable and is thus unsuitable for the monitoring of Ph-positive
      cells during therapy. Interphase fluorescence in situ hybridization (iFISH)
      allows analysis of a large number of cells (> 500) in a timely and efficiently
      quantitative manner. We obtained 118 peripheral blood (PB) and 127 bone marrow
      (BM) samples from 75 adult chronic myelogenous leukemia (CML) patients undergoing
      stem cell transplantation. We simultaneously performed nested RT-PCR and iFISH
      for all samples. False-positive cells were detected in 2.48% +/- 0.93% (mean +/-
      SD) of PB samples and 2.75% +/- 0.83% of BM samples. The iFISH results for PB and
      BM ranged from 1.4% to 92.8% and 1.0% to 93.8%, respectively. Correlation
      analysis of iFISH results for PB versus BM samples showed a strong relation (r =
      .993). A significant correlation (P < .05) was also found between iFISH and first
      round RT-PCR. The sensitivity of BCR-ABL iFISH was similar to that of first-round
      RT-PCR, and iFISH results for PB and BM were also well correlated. Thus, iFISH
      analysis of PB and/or BM samples may be more clinically reliable than RT-PCR in
      the quantitative monitoring of BCR-ABL fusion in CML after transplantation.

PMID- 12215019
TI  - Risk of neutropenic fever and early infectious complications after autologous
      peripheral blood stem cell transplantation for malignant diseases.
AB  - Autologous peripheral blood stem cell transplantation (auto-PBSCT) has
      facilitated high-dose chemotherapy for the treatment of various types of
      malignancy, but the factors affecting the treatment outcome have not been well
      defined. We evaluated patients who underwent auto-PBSCT (46 patients with
      hematological malignancies and 39 with solid tumors) to elucidate the risks of
      background factors, including age, in association with infectious complications.
      In contrast to former reports, faster engraftment did not influence the incidence
      of documented infection or neutropenic fever, whereas high age (age > or = 50
      years old) and delayed platelet recovery (> or = 18 days) were demonstrated to be
      positively involved. The odds ratio (OR) for documented infection in elderly
      patients was 4.94 (95% confidence interval, 1.22-15.8). Another risk factor of
      infection was the HD-ICE regimen (ifosfamide, carboplatin, etoposide) given to
      patients with solid tumors (OR, 8.00; 95% confidence interval, 1.61-39.7). In
      conclusion, we found that elderly patients and patients on the HD-ICE regimen
      have a higher risk of infectious complications even after auto-PBSCT. Although
      the clinical indications for auto-PBSCT can be extended to elderly patients,
      thorough precautions should be taken against infectious complications during the
      pre-engraftment phase.

PMID- 12215020
TI  - Impaired fibrinolytic capacity in rheumatic mitral stenosis with or without
      atrial fibrillation and nonrheumatic atrial fibrillation.
AB  - Chronic atrial fibrillation (AF) has often been associated with systemic
      embolization, and patients with mitral stenosis (MS) have the highest
      thromboembolic risk. Increased risk of thromboembolism could be in part due to
      impaired fibrinolytic function. Global fibrinolytic capacity (GFC) is an
      innovative technique for evaluating the entire fibrinolytic system. The aim of
      our study was to evaluate fibrinolytic activity in patients with rheumatic and
      nonrheumatic chronic AE To investigate fibrinolytic activity, we assessed GFC in
      peripheral blood samples of 32 patients with nonrheumatic AF (14 women; mean age,
      56 +/- 1 years), 30 patients with rheumatic MS and AF (23 women; mean age, 35 +/-
      9 years), and 32 patients with rheumatic MS and sinus rhythm (24 women; mean age,
      36 +/- 8 years). The control group comprised 30 healthy adult subjects in normal
      sinus rhythm. Patients with chronic AF (rheumatic and nonrheumatic) had lower GFC
      than did the controls (P = .0001). The rheumatic AF group also showed decreased
      levels of GFC compared with the nonrheumatic AF group, with the rheumatic MS and
      sinus rhythm group, and with controls (P = .03, P = .02, P = .0001,
      respectively). GFC was lower in patients with rheumatic MS and sinus rhythm than
      in controls (P = .003). Although there were correlations between GFC and mitral
      valve area, transmitral mean gradient, left atrial diameter, and mitral
      calcification in patients with rheumatic MS, multivariate analysis showed only
      transmitral gradient as an independent factor affecting GFC. Patients with AF
      have decreased GFC, a finding that suggests the presence of a hypofibrinolytic
      state. Fibrinolytic dysfunction was more pronounced in rheumatic MS patients with
      AF than in those with nonrheumatic AF. Moreover, patients with rheumatic MS and
      sinus rhythm had decreased global fibrinolytic activity. Hypofibrinolysis
      documented by decreased GFC can be one of the important causes of increased risk
      of embolism in patients with AF and rheumatic MS.

PMID- 12215021
TI  - Development of diffuse large cell lymphoma from follicular lymphoma with multiple
      immunoglobulin heavy chain gene rearrangement occurring in a patient with Wiskott
      Aldrich syndrome.

PMID- 12215022
TI  - Robot-assisted surgical systems: a new era in laparoscopic surgery.
AB  - The introduction of laparoscopic surgery offers clear advantages to patients; to
      surgeons, it presents the challenge of learning new remote operating techniques
      quite different from traditional operating. Telemanipulation, introduced in the
      late 1990s, was a major advance in overcoming the reduced dexterity introduced by
      laparoscopic techniques. This paper reviews the development of robotic systems in
      surgery and their role in the operating room of the future.

PMID- 12215023
TI  - Problem-based learning for surgical trainees.
AB  - Problem-based learning (PBL) represents an educational technique that many
      medical schools have adopted for their undergraduate curricula. This article
      discusses the application of PBL for surgical trainees.

PMID- 12215024
TI  - Aide memoire for the management of gunshot wounds.
AB  - The hospitals in Johannesburg deal with about 4,000 gunshot wounds a year.
      Although most are from hand guns, a number are from high velocity, military-type
      weapons. Extensive experience has been built up and many lessons learned.
      Attention is directed to the actual damage inflicted rather than on theoretical
      predictions based on presumed velocity of the bullets involved, as this can often
      be misleading. Some patients are delayed in their presentation to emergency
      departments, in other cases several gunshot wound patients arrive at the same
      time, requiring appropriate triage and urgent management.

PMID- 12215025
TI  - Rhys-Davies exsanguinator: effect of age and inflation on performance.
AB  - We found that the Rhys-Davies exsanguinators in our local hospitals were poorly
      maintained (inflation pressure, storage conditions, replacement age) when
      compared to the manufacturers' recommendations. In a volunteer study, we
      demonstrate how the inflation pressure and age of an exsanguinator affect its
      performance.

PMID- 12215026
TI  - Aortic aneurysms, inflammatory pathways and nitric oxide.
AB  - The Leicester experience of treatment of aortic aneurysms indicates that workload
      is increasing. Despite an increase in elective repairs, the number of ruptured
      abdominal aortic aneurysms is also increasing. The mortality of ruptured
      abdominal aortic aneurysm remains static despite advances in critical care
      medicine. Multi-organ failure is the commonest cause of death following ruptured
      abdominal aortic aneurysm and the systemic inflammatory response syndrome,
      ischaemia-reperfusion injury and activation of inflammatory pathways are
      important precursors. Organ failure, reperfusion injury and inflammatory pathway
      activation can be studied at a cellular and biochemical level in animal models of
      aortic cross-clamping. The nitric oxide response is an important component of the
      inflammatory response and augmentation of the NO response may protect against
      renal injury caused by aortic cross-clamping during aortic aneurysm repair.

PMID- 12215027
TI  - A retrospective review of pharyngeal pouch surgery in 56 patients.
AB  - We retrospectively reviewed 56 consecutive patients treated surgically for a
      pharyngeal pouch at our institution between 1989-1999 (10 years). Various
      surgical procedures were performed including endoscopic stapling (20), external
      excision (23), Dohlman's procedure (9), pouch inversion (3), cricopharyngeal
      myotomy only (3), and pouch suspension (1). There were 12 patients (18%) with
      complications and one mortality (2%). Four patients (7%) had a recurrence with 2
      requiring further surgery. Over the latter 3 years, endoscopic stapling has
      emerged as the primary procedure for pharyngeal pouch surgery in our unit; with
      the advantages of an earlier commencement of diet and earlier hospital discharge.
      However, results were not as good as for external excisions. Furthermore, there
      were difficulties with 3 cases that commenced as endoscopic stapling procedures
      but had to he converted to external excisions due to inaccessibility in one case
      and iatrogenic perforations in two cases. As with any new technique, problems may
      occur and a learning curve has been appreciated in our unit. Surgeons must he
      prepared, with informed consent, to convert to an external approach should
      difficulties arise during endoscopic stapling. Elderly and frail patients who are
      at risk from a general anaesthetic may benefit from endoscopic stapling. External
      excision of pharyngeal pouches may be more appropriate in the young, the
      medically fit, and when malignancy is a concern.

PMID- 12215028
TI  - Challenging embryological theories on congenital diaphragmatic hernia: future
      therapeutic implications for paediatric surgery.
AB  - Lung hypoplasia is central to the poor prognosis of babies with congenital
      diaphragmatic hernia (CDH). Prolapse of abdominal organs through a diaphragmatic
      defect has traditionally been thought to impair lung growth by compression. The
      precise developmental biology of CDH remains unresolved. Refractory to fetal
      correction, lung hypoplasia in CDH may instead originate during embryogenesis and
      before visceral herniation. Resolving these conflicting hypotheses may lead to
      reappraisal of current clinical strategies. Genetic studies in murine models and
      the fruitfly, Drosophila melanogaster are elucidating the control of normal
      respiratory organogenesis. Branchless and breathless are Drosophila mutants
      lacking fibroblast growth factor (FGF) and its cognate receptor (FGFR),
      respectively. Sugarless and sulphateless mutants lack enzymes essential for
      heparan sulphate (HS) biosynthesis. Phenotypically, all these mutants share
      abrogated airway branching. Mammalian organ culture and transgenic models confirm
      the essential interaction of FGFs and HS during airway ramification. Embryonic
      airway development (branching morphogenesis) occurs in a defined spatiotemporal
      sequence. Unlike the surgically-created lamb model, the nitrofen rat model
      permits investigation of embryonic lung growth in CDH. Microdissecting embryonic
      lung primordia from the nitrofen CDH model and normal controls, we demonstrated
      that disruption of stereotyped airway branching correlates with and precedes
      subsequent CDH formation. To examine disturbed branching morphogenesis
      longitudinally, we characterised a system that preserves lung hypoplasia in organ
      culture. We tested FGFs and heparin (an HS analogue) as potential therapies on
      normal and hypoplastic lungs. Observing striking differences in morphological
      response to FGFs between normal and hypoplastic lung primordia, we postulated
      abnormalities of FGF/HS signalling in the embryonic CDH lung. Evaluating this
      hypothesis further, we examined effects of an HS-independent growth factor
      (epidermal growth factor, EGF) on hypoplastic lung development. Visible
      differences in morphological response indicate an intrinsic abnormality of
      hypoplastic lung primordia that may involve shared targets of FGFs and EGE. These
      studies indicate that lung hypoplasia precedes diaphragmatic hernia and may
      involve disturbances of mitogenic signalling pathways fundamental to embryonic
      lung development. What does this imply for human CDH? Fetal surgery may be 'too
      little, too late' to correct an established lung embryopathy. In utero growth
      factor therapy may permit antenatal lung rescue. Prevention of the birth defect
      by preconceptual prophylaxis may represent the ultimate solution.

PMID- 12215029
TI  - Improving colorectal cancer follow-up: the dedicated single-visit colorectal
      cancer follow-up clinic.
AB  - OBJECTIVE: To assess the effectiveness of the dedicated single-visit colorectal
      cancer follow-up clinic in improving postoperative surveillance. PATIENTS AND
      METHODS: Data of follow-up of 137 consecutive patients with colorectal cancer
      treated by the senior author over a 3 year period were obtained. Surveillance
      over three periods in time were analysed: (i) before the establishment of a
      protocol; (ii) following the implementation of a protocol for follow-up of
      colorectal cancer with liver ultrasound and colonoscopy; and (iii) following the
      establishment of the dedicated single-visit colorectal cancer follow-up clinic.
      RESULTS: The single-visit colorectal cancer follow-up clinic has reduced the mean
      time to the interventions (from 12.1 months to 6.0 months for the liver
      ultrasound and from 8.7 months to 6.4 months for the colonoscopy). In addition,
      the percentage of patients having their liver ultrasound within the targeted time
      has increased from 14% to 55%. The percentage of patients having their
      colonoscopy within the targeted time has also increased from 50% to 77%. The
      percentage who missed their liver ultrasound has been reduced from 57% to 0%. The
      percentage of patients who missed their colonoscopy has also been reduced from
      36% to 3%. CONCLUSION: The dedicated single-visit colorectal cancer follow-up
      clinic improves the postoperative surveillance of patients with colorectal
      cancer.

PMID- 12215030
TI  - Formalin dab for haemorrhagic radiation proctitis.
AB  - BACKGROUND: Haemorrhagic radiation proctitis frequently presents as a problem in
      management. We analysed the technique of formalin dab in its management. PATIENTS
      AND METHODS: Twenty patients presenting with haemorrhagic radiation proctitis and
      treated with formalin dab were prospectively analysed. RESULTS: Twelve patients
      ceased to bleed following one session of formnalin dab. Six patients needed more
      than one session to effect haemostasis. Two of three patients with torrential
      bleeding failed to respond to formalin dab and required surgical excision of the
      rectum. CONCLUSION: Formalin dab is a simple, effective and safe treatment
      modality in the management of chronic haemorrhagic radiation proctitis, and hence
      should be considered as the initial treatment modality for such a condition.

PMID- 12215031
TI  - Accuracy of clinical diagnosis in knee arthroscopy.
AB  - A prospective study of 238 patients was performed in a district general hospital
      to assess current diagnostic accuracy rates and to ascertain the use and the
      effectiveness of magnetic resonance imaging (MRI) scanning in reducing the number
      of negative arthroscopies. The pre-operative diagnosis of patients listed for
      knee arthroscopy was medial meniscus tear 94 (40%) and osteoarthritis 59 (25%).
      MRI scans were requested in 57 patients (24%) with medial meniscus tear
      representing 65% (37 patients). The correlation study was done between pre
      operative diagnosis, MRI and arthroscopic diagnosis. Clinical diagnosis was as
      accurate as the MRI with 79% agreement between the preoperative diagnosis and
      arthroscopy compared to 77% agreement between MRI scan and arthroscopy. There was
      no evidence, in this study, that MRI scan can reduce the number of negative
      arthroscopies. Four normal MRI scans had positive arthroscopic diagnosis (two
      torn medial meniscus, one torn lateral meniscus and one chondromalacia patella).
      Out of 240 arthroscopies, there were only 10 normal knees (negative arthroscopy)
      representing 4% of the total number of knee arthroscopies; one patient of those
      10 cases had MRI scan with ACL rupture diagnosis.

PMID- 12215032
TI  - An audit on the blood transfusion requirements for revision hip arthroplasty.
AB  - The hospital transfusion committee of Swindon and Marlborough NHS Trust had
      formulated a maximum surgical blood ordering schedule (MSBOS) which included the
      standard practice of 6 units of blood for revision hip arthroplasty. A
      retrospective audit of 73 patients who underwent revision hip arthroplasty over a
      year was undertaken to identify current practice and to ensure that the standard
      was adequate for patient safety. Information regarding the number of units
      requested, number of units transfused, pre-operative haemoglobin (Hb), lowest
      postoperative Hb and number of additional units of blood requested within 3 days
      postoperatively, was collected from patients' case-notes. Of the 73 patients,
      80.3% received less than 6 units, 12.2% received 6 units and 7.5% received more
      than 6 units. Based on pre-operative Hb, blood usage was analysed. Of cross
      matched units, 92.3% were used when pre-operative Hb was < 12 g/dl, 64.4% were
      used when Hb was between 12.1-13.0 g/dl, 54.3% were used when the Hb was between
      13.1-14.0 g/dl, 38.9% were used when Hb was between 14.1-15.0 g/dl and 39.7% used
      with pre-operative Hb of > 15.0 g/dl. Of the total, 14 patients had a
      postoperative Hb of < 9 g/dl for whom additional units of blood were ordered and
      given to achieve a Hb of between 10.1-14.2 g/dl prior to discharge. This audit
      suggests that in patients with pre-operative Hb of 13 g/dl or more, the cross
      match could be 4 units instead of 6 units for revisions.

PMID- 12215033
TI  - A 25-year study of emergency surgical admissions.
AB  - BACKGROUND: Numbers of emergencies are increasing, but no comprehensive data are
      available for emergency surgical admissions. This study documents the changes
      over 25 years in a district general hospital. METHODS: Details of all general
      surgical (including urological) emergency admissions were analysed for every
      fourth calendar year from 1974 to 1998. RESULTS: A total of 19,931 patients were
      admitted during the 7 years studied, rising from 2137 in 1974 to 3578 in 1994
      (3377 in 1998). Mean age increased from 47.9 years to 52.6 years while mean
      length of stay fell from 9.5 days to 5.3 days. Hospital mortality decreased from
      6.6% to 3.7%. When calculated per 100,000 population, the increase in admission
      rate was significant (P < 0.001) but bed requirements did not increase despite
      the increase in workload. Several diagnoses became significantly more frequent
      (ruptured aortic aneurysm, gallstones, constipation, cutaneous abscess,
      diverticular disease, gastroenteritis, non-specific abdominal pain, pilonidal
      sinus and urinary diagnoses). Appendicitis and non-malignant intestinal
      obstruction became significantly less common. CONCLUSIONS: This study has
      documented a progressive increase in surgical admissions. Despite increasing age
      of patients, lengths of stay and hospital mortality have decreased.

PMID- 12215034
TI  - Suturing: a lost art.

PMID- 12215035
TI  - New doctors in emergency medicine: can they suture?

PMID- 12215036
TI  - A simple, safe and effective method for laparoscopic port closure.

PMID- 12215037
TI  - Umbilical port closure under direct vision.

PMID- 12215038
TI  - A review of the management of small bowel obstruction.

PMID- 12215039
TI  - The use of a proforma improves colorectal cancer pathology reporting.

PMID- 12215040
TI  - Should we continue oesophageal surgery in a district general hospital?

PMID- 12215041
TI  - Transmetatarsal amputation: an 8-year experience.

PMID- 12215042
TI  - Should we continue oesophageal surgery in a district general hospital? A review
      of 200 consecutive cases.

PMID- 12215043
TI  - Should we continue oesophageal surgery in a district general hospital? A review
      of 200 consecutive cases.

PMID- 12215044
TI  - Should we continue oesophageal surgery in a district general hospital? A review
      of 200 consecutive cases.

PMID- 12215045
TI  - Should we continue oesophageal surgery in a district general hospital? A review
      of 200 consecutive cases.

PMID- 12215046
TI  - Acute gallstone pancreatitis in childhood.

PMID- 12215048
TI  - Use of ferric chloride to identify salicylate-containing poisons.
AB  - OBJECTIVE: Ferric chloride (FeCl3) is used to qualitatively test the urine of
      patients with presumed salicylate exposure. FeCl3 testing of an unidentified
      poison might provide evidence of salicylate exposure in situations where FeCl3
      urine testing cannot be used. Such situations include the absence of a urine
      sample, immediately after ingestion before urine contains a detectable quantity
      of salicylate, or for patients chronically using salicylatesfor which FeCl3
      testing is unhelpful. This study seeks to determine if FeCl3 can be used to
      identify salicylate-containing products. METHODS: We assessed the reactivity of
      FeCl3 with commercially available salicylate-containing products. We applied 0.1
      mL of 10% FeCl3 solution to each of 15 various salicylate-containing products
      including: regular and buffered acetylsalicylic acid, bismuth subsalicylate,
      methylsalicylate, physostigmine salicylate, salicylic acid, trolamine salicylate,
      and herbal tablets with salicin-containing white willow bark (Salix sp.). These
      products tested were: regular and enteric-coatedpills (n = 4), powder (n = 1),
      topical creams (n = 5), topical liquids (n = 4), and intravenous solution (n =
      1). FeCl3 was applied to crushed tablets and added directly to liquids and
      creams. Fifteen salicylate-free controls including liquids, pills, and creams
      similar in appearance to experimental samples were also tested. Three blinded
      physiciansfamiliar with FeCl3 testing independently observed the addition of
      FeCl3 to each sample and rated a positive or negative result. RESULTS: All
      salicylate-containing products were interpreted to be clearly FeCl3 positive and
      all control samples were interpreted to be clearly FeCl3 negative. CONCLUSION:
      Salicylate-containing products may be identified using FeCl33. When using FeCl3

PMID- 12215047
TI  - Cocaethylene's effects on coronary artery blood flow and cardiac function in a
      canine model.
AB  - OBJECTIVES: Cocaethylene is a toxic metabolite of cocaine formed in the presence
      of ethanol. Though cocaine causes coronary vasoconstriction, cocaethylene's
      effects on coronaryflow are unknown. The aim of our study was to describe
      cocaethylene 's effects on coronary flow and cardiac function. METHODS: Sixteen
      alpha-chloralose anesthetized dogs were monitored with Swan-Ganz, arterial and
      venous catheters, and an electrocardiogram. Dopplerflow probes were placed on the
      circumflex and left anterior descending coronary arteries. Dogs were allotted 15
      mg/kg (n = 10) or 30mg/kg (n = 6) of cocaethylene given as a continuous
      intravenous infusion. Measurements were made at fixed time intervals during the
      60-minute cocaethylene infusion and 2-hour observation period. RESULTS: The
      cocaethylene concentrations were maximal at the end of the infusion and
      cocaethylene was rapidly metabolized to benzoylecognine. One low-dose animal died
      of ventricular fibrillation. Five high-dose dogs experienced ventricular
      arrhythmias or pulseless electrical activity (PEA), and three died. In the low
      dose group, cocaethylene caused a 38% increase in mean arterial pressure relative
      to baseline, and increased systemic vascular resistance. In the high-dose group,
      at maximal cocaethylene concentrations, stroke volume decreased by 42% (p <
      0.0002), and circumflex blood flow decreased by 30% (p = 0.03) relative to
      baseline, when arrhythmias occurred. The PR, QRS, and QTc intervals increased by
      48, 209, and 29%, respectively (p < 0.001). As cocaethylene levels declined,
      circumflex blood flow increased by 77% (p = 0.05) and mean arterial pressure
      increased 49% (p < 0.01), also relative to baseline. CONCLUSIONS: Cocaethylene
      caused hypertension and increased systemic vascular resistance. At high
      concentrations, it decreased myocardial function, slowed cardiac conduction, and
      was arrhythmogenic. The cocaethylene's toxicity does not appear to be mediated by
      effects on coronary blood flow.

PMID- 12215049
TI  - The National Poisons Information Centre in Sri Lanka: the first ten years.
AB  - INTRODUCTION: Poisoning is a major health concern in Sri Lanka, which has a very
      high morbidity and mortality from pesticide poisoning. Poisoning, which continues
      to be in the first five leading causes of death, accounts for about 80,000
      hospitalizations and over 3,000 deaths per year. The National Poisons Information
      Centre in Sri Lanka, thefirst such centre to be established in South Asia,
      completed 10 years service in 1997. The 4,070 calls received in thefirst 10 years
      are analyzed and compared with the national hospitalization pattern. METHODS: The
      recorded data sheets of all enquiries received from 1988 to 1997 were analyzed
      retrospectively to study (1) purpose of enquiry, (2) category of enquirer, (3)
      circumstances of poisoning, (4) gender of victim, (5) age of victim, (6) type of
      poison, and (7) outcome. Items (6) and (7) were compared with the national
      hospital statistics for 1998. RESULTS: Of the 4,070 enquiries, 92% concerned
      specific patients and 6% were for information on poisons. Almost 90% of the
      enquiries were from medical or paramedical personnel, 5% from relatives or
      friends, and 3% from the victims. Nearly 38% of enquiries concerned pesticides
      compared to 27% of poisoning hospitalizations. Medicinal agents were the subject
      of 20% of enquiries compared to 13% of hospitalizations. The major discrepancy
      was for snake bites, accounting for only 6% of enquiries but 42% of
      hospitalizations. Sex distribution of enquiries showed more males than females.
      Thirty-seven percent of the victims were young adults-15-29years age group.
      Nearly 49% of the enquiries were for suicidal attempts. Seventy-one percent of
      the victims recovered. CONCLUSIONS: Although enquiries to the NPIC averaged only
      0.5% of poisoning hospitalizations, they were sufficiently representative of the
      national pattern to predict that increasing utilization of the NPIC would offer a
      much needed service, both for

PMID- 12215050
TI  - Intrathecal vincristine: fatal myeloencephalopathy despite cerebrospinal fluid
      perfusion.
AB  - BACKGROUND: Vincristine, an antineoplastic agent, must never be injected
      intrathecally because of its devastating neurotoxic effects, which are usually
      fatal. We report a case of fatal myeloencephalopathy secondary to inadvertent
      intrathecal administration of vincristine. CASE REPORT: Intrathecal vincristine
      was inadvertently injected into a twelve-year-old girl with acute lymphocytic
      leukemia. The error was immediately recognized and treated with
      cerebrospinalfluid drainage and cerebrospinal fluid exchange. Clinical evolution
      during the 83 days until death is described Multiple samples of cerebrospinal
      fluid were assayed for vincristine sulfate. Neuropathological post-mortem changes
      in the brain and spinal cord are reported CONCLUSION: We compare our case with
      other previously reported cases in which patient survival was achieved with the
      same treatment. We summarize preventive measures to avoid such unfortunate
      occurrences.

PMID- 12215051
TI  - Parotitis due to organophosphate intoxication.
AB  - Acute pancreatitis due to pancreatic exocrine over-secretion induced by
      organophosphate poisoning has been previously reported but parotid gland
      involvement has not. This paper describes a case of acute organophosphate-induced
      parotitis in a patient with pre-existing sialolithiasis. The patient developed
      bilateral facial swelling in the pre-auricular area extending to the angle of the
      jaw and also developed elevated serum amylase on the second day of the poisoning.
      Serum lipase remained normal. Autopsy confirmed parotid gland inflammation and
      pre-existing ductal lithiasis. This case illustrates that organophosphate-induced
      parotitis can occur and should be considered in patients with organophosphate
      poisoning who have hyperamylasemia without elevation in serum lipase.

PMID- 12215052
TI  - Delivery of poisons information to health professionals: telephone or Internet?
      The Scottish experience.

PMID- 12215053
TI  - Zaleplon-induced coma and bluish-green urine: possible antidotal effect by
      flumazenil.

PMID- 12215054
TI  - Envenomation by the Vietnamese centipede in a Long Island pet store.

PMID- 12215055
TI  - Management of patients with acute coronary syndromes: what is the clinical role
      of direct thrombin inhibitors?
AB  - Despite important pharmacokinetic and biological advantages of direct thrombin
      inhibitors over heparin, early randomised trials failed to demonstrate a clear
      net clinical benefit of these agents compared with heparin because of a higher
      bleeding risk, particularly with hirudin, and only modest efficacy gains. More
      recently, however, a systematic review of the direct thrombin inhibitor trials
      based on individual patient data as well as the results of the 17 000-patient
      Hirulog Early Reperfusion or Occlusion (HERO)-2 trial have confirmed the
      superiority of both hirudin and bivalirudin over unfractionated heparin in
      patients with acute coronary syndromes and undergoing percutaneous coronary
      intervention. Ongoing trials should further clarify the role of bivalirudin in
      patients undergoing percutaneous coronary intervention in the context of
      glycoprotein IIb/IIIa inhibitor use, while additional studies are required to
      define the role of direct thrombin inhibitors used in conjunction with other
      newer antithrombotic and/or thrombolytic strategies in patients with acute
      coronary syndromes.

PMID- 12215056
TI  - Focus on new drugs in development against human cytomegalovirus.
AB  - The limitations of current therapies for human cytomegalovirus (HCMV) coupled
      with the continued impact of HCMV disease in the immunocompromised host are the
      driving force for the development of new drugs against HCMV. This review
      predominantly focuses on new non-DNA polymerase inhibitors of HCMV replication.
      Drugs such as tomeglovir (BAY-384766), 2-bromo-5,6-dichloro-1beta-D-ribofuranosyl
      benzimidazole (BDCRB) and GW-275175X act as inhibitors of the terminase complex
      that is involved in cleavage and packaging of the unit length DNA into the
      capsids. Although the viral protein kinase UL97 has been exploited as an
      activator of ganciclovir and its prodrug valganciclovir, a new inhibitor
      maribavir (benzamidavir) has been shown to be a highly potent inhibitor of this
      enzyme. Many of these compounds have undergone successful phase I clinical
      trials. There are other compounds which have been identified through drug
      screening but are at the earlier stages of development.

PMID- 12215057
TI  - Management of bacterial urinary tract infections in adult patients with diabetes
      mellitus.
AB  - Urinary tract infections (UTIs) are more common and tend to have a more
      complicated course in patients with diabetes mellitus than in the general
      population. The mechanisms that potentially contribute to the increased
      prevalence of both asymptomatic and symptomatic bacteriuria in these patients are
      defects in the local urinary cytokine secretions and an increased adherence of
      the microorganisms to the uroepithelial cells. The need for treatment of
      asymptomatic bacteriuria remains controversial. No evidence is available on the
      optimal treatment of acute cystitis and pyelonephritis in patients with diabetes.
      Because of the frequent (asymptomatic) upper tract involvement and the possible
      serious complications, many experts recommend a 7- to 14-day oral antibacterial
      regimen for bacterial cystitis in these patients, with an antibacterial agent
      that achieves high concentrations both in the urine and in urinary tract tissues.
      The recommended treatment of acute pyelonephritis does not differ from that in
      patients without diabetes. Clinical trials specifically dealing with the
      treatment of UTIs in patients with diabetes, comparing the optimal duration and
      choice of antibacterial agent, are needed. In addition, new approaches to
      preventive strategies must prove their value in this specific patient group.

PMID- 12215059
TI  - Airmax: a multi-dose dry powder inhaler.
AB  - Airmax is a multi-dose dry powder inhaler. An internal pump measures out the drug
      dose using controlled air pressure. Inhalation transports the drug into a cyclone
      separator (where active drug is separated from the lactose carrier) and then into
      the patient airway. In vitro studies indicate that Airmax may be less dependent
      on airflow than Turbuhaler for drug delivery; greater dose consistency was seen
      with administration of budesonide via Airmax than via Turbuhaler. At a low flow
      rate, the lung deposition of budesonide administered via Airmax was greater than
      that of budesonide administered via Turbuhaler or a pressurised metered dose
      inhaler in patients with asthma. In cumulative-dose studies, the mean forced
      expiratory volume in 1 second (FEV(1)) achieved with salbutamol (albuterol) or
      formoterol administered via Airmax was equivalent to that achieved with twice the
      dose administered via dry powder inhalers. black triangle In randomised, double
      blind studies, budesonide administration via Airmax was equivalent to
      administration via Turbuhaler with regards to FEV(1) and improvement in asthma
      symptoms in both adults and children with asthma. The concentration of adenosine
      monophosphate producing a 20% fall in FEV(1) increased from pretreatment levels
      by a greater extent with budesonide administered via Airmax, compared with
      Turbuhaler. Both adults and children preferred Airmax to Turbuhaler, and more
      found Airmax easier to use. In one study, the majority of children found learning
      how to use Airmax trade mark easier than learning how to use Turbuhaler.

PMID- 12215058
TI  - Selective serotonin reuptake inhibitors for premenstrual dysphoric disorder: the
      emerging gold standard?
AB  - There have been a large number of studies conducted investigating the use of
      selective serotonin reuptake inhibitors (SSRIs) in the treatment of patients with
      premenstrual dysphoric disorder (PMDD). The 12 randomised, controlled trials with
      continuous dose administration of SSRIs and the eight randomised, controlled
      trials with luteal phase dose administration (from ovulation to menses) are
      reviewed. All the treatment studies on fluoxetine, sertraline, paroxetine and
      citalopram have reported positive efficacy. Fluoxetine and sertraline have the
      largest literature, with a smaller number of studies endorsing paroxetine and
      citalopram. Mixed efficacy results have been reported with fluvoxamine. In
      general, adverse effects from the use of SSRIs in women with PMDD are the usual
      mild and transient adverse effects from SSRIs including anxiety, dizziness,
      insomnia, sedation, nausea and headache. Sexual dysfunction and weight gain can
      be problematic long-term adverse effects of SSRIs, but these effects have not
      been systematically evaluated with long-term SSRI use in women with PMDD.
      Serotonergic antidepressants have differential superiority over nonserotonergic
      antidepressants in the treatment of PMDD. Treatments that enhance serotonergic
      action improve premenstrual irritability and dysphoria with a rapid onset of
      action, suggesting a different mechanism of action than in the treatment of
      depression. It is possible that neurosteroids, such as progesterone metabolites,
      are involved in the rapid action of serotonergic antidepressants in PMDD. Future
      research needs to address less frequent dose administration regimens, such as
      'symptom-onset' dose administration, and the recommended length of treatment.

PMID- 12215063
TI  - Dexmethylphenidate.
AB  - Dexmethylphenidate comprises only the d-enantiomer (the pharmacologically
      effective isomer) of racemic methylphenidate and is indicated for the treatment
      of patients aged > or =6 years with attention deficit hyperactivity disorder
      (ADHD). In a 4-week, double-blind trial in 132 children with ADHD, significantly
      greater improvements from baseline in teacher-rated Swanson, Nolan and Pelham
      (SNAP)-ADHD scores were seen in dexmethylphenidate and methylphenidate
      recipients, compared with placebo recipients. In addition, significantly more
      dexmethylphenidate and methylphenidate recipients, compared with placebo
      recipients, were much improved or very much improved according to Clinical Global
      Impression-Improvement of Illness scale scores. In the same study, parent-rated
      SNAP-ADHD scores had decreased by a significantly greater extent in
      dexmethylphenidate recipients at 3pm and 6pm and in methylphenidate recipients at
      3pm, compared with placebo recipients. Significantly fewer dexmethylphenidate
      than placebo recipients failed treatment in a double-blind, treatment-withdrawal
      trial in 75 children with ADHD (17.1 vs 61.5%). In a noncomparative study in 22
      children with ADHD, symptoms of ADHD, as assessed by teachers and parents, were
      controlled during the entire school day in 68 and 86% of dexmethylphenidate
      recipients, respectively, with a median duration of effect of 6.3 and 7.5 hours,
      respectively. Dexmethylphenidate was generally well tolerated in children with
      ADHD; adverse events were consistent with those known to be associated with
      agents containing methylphenidate.

PMID- 12215067
TI  - Micronised fenofibrate: an updated review of its clinical efficacy in the
      management of dyslipidaemia.
AB  - Micronised fenofibrate is a synthetic phenoxy-isobutyric acid derivative (fibric
      acid derivative) indicated for the treatment of dyslipidaemia. Recently, a new
      tablet formulation of micronised fenofibrate has become available with greater
      bioavailability than the older capsule formulation. The micronised fenofibrate
      160mg tablet is bioequivalent to the 200mg capsule. The lipid-modifying profile
      of micronised fenofibrate 160mg (tablet) or 200mg (capsule) once daily is
      characterised by a decrease in low-density lipoprotein cholesterol (LDL-C) and
      total cholesterol (TC) levels, a marked reduction in plasma triglyceride (TG)
      levels and an increase in high-density lipoprotein cholesterol (HDL-C) levels.
      Micronised fenofibrate 200mg (capsule) once daily produced greater improvements
      in TG and, generally, in HDL-C levels than the hydroxymethylglutaryl coenzyme A
      reductase inhibitors simvastatin 10 or 20 mg/day, pravastatin 20 mg/day or
      atorvastatin 10 or 40 mg/day. Combination therapy with micronised fenofibrate
      200mg (capsule) once daily plus fluvastatin 20 or 40 mg/day or atorvastatin 40
      mg/day was associated with greater reductions from baseline than micronised
      fenofibrate alone in TC and LDL-C levels. Similar or greater changes in HDL-C and
      TG levels were seen in combination therapy, compared with monotherapy,
      recipients. Micronised fenofibrate 200mg (capsule) once daily was associated with
      significantly greater improvements from baseline in TC, LDL-C, HDL-C and TG
      levels than placebo in patients with type 2 diabetes mellitus enrolled in the
      double-blind, randomised Diabetes Atherosclerosis Intervention Study (DAIS) [> or
      =3 years follow-up]. Moreover, angiography showed micronised fenofibrate was
      associated with significantly less progression of coronary atherosclerosis than
      placebo. Micronised fenofibrate has also shown efficacy in patients with
      metabolic syndrome, patients with HIV infection and protease inhibitor-induced
      hypertriglyceridaemia and patients with dyslipidaemia secondary to heart
      transplantation. Micronised fenofibrate was generally well tolerated in clinical
      trials. The results of a large (n = 9884) 12-week study indicated that
      gastrointestinal disorders are the most frequent adverse events associated with
      micronised fenofibrate therapy. Elevations in serum transaminase and creatine
      phosphokinase levels have been reported rarely with micronised fenofibrate. In
      conclusion, micronised fenofibrate improves lipid levels in patients with primary
      dyslipidaemia; the drug has particular efficacy with regards to reducing TG
      levels and raising HDL-C levels. Micronised fenofibrate is also effective in
      diabetic dyslipidaemia; as well as improving lipid levels, the drug reduced
      progression of coronary atherosclerosis in patients with type 2 diabetes
      mellitus. The results of large ongoing studies (e.g. FIELD with approximately 10
      000 patients) will clarify whether the beneficial lipid-modifying effects of
      micronised fenofibrate result in a reduction in cardiovascular morbidity and
      mortality.

PMID- 12215068
TI  - Insulin aspart: a review of its use in the management of type 1 and 2 diabetes
      mellitus.
AB  - Insulin aspart, a rapid-acting human insulin analogue, provides more rapid
      absorption than regular human insulin after subcutaneous administration. In most
      randomised, nonblind clinical trials in patients with type 1 diabetes mellitus,
      insulin aspart administered immediately before meals resulted in significantly
      lower mean glycosylated haemoglobin A(1c ) (HbA(1c)) levels than regular human
      insulin (usually administered 30 minutes before a meal). Insulin aspart also
      significantly improved postprandial glycaemic control compared with regular human
      insulin. The efficacy of insulin aspart was similar to that of insulin lispro
      when administered to patients with type 1 diabetes mellitus via continuous
      subcutaneous infusion in a randomised, nonblind trial. Preliminary data from
      randomised, nonblind trials suggest insulin aspart had a trend towards lower
      HbA(1c) levels compared with regular human insulin in patients with type 2
      diabetes mellitus. Biphasic insulin aspart [30% soluble (rapid-acting) and 70%
      protamine-bound insulin aspart (BIAsp30)] generally provided significantly better
      postprandial glucose control than a similar mixture of biphasic regular human
      insulin (BHI30) in a randomised, nonblind trial in patients with type 1 or 2
      diabetes mellitus. However, the long-term efficacy of BIAsp30 was similar to that
      of BHI30 after 2 years in a randomised, nonblind trial in patients with type 2
      diabetes mellitus. Patients with type 1 or 2 diabetes mellitus reported greater
      treatment satisfaction with insulin aspart or BIAsp30 than with regular human
      insulin or BHI30. The overall incidence of hypoglycaemia with insulin aspart was
      lower than, or similar to, that of regular human insulin. Moreover, insulin
      aspart tended to be associated with a lower occurrence of nocturnal hypoglycaemia
      and severe hypoglycaemic events than regular human insulin. CONCLUSION: The
      standard preparation of insulin aspart has the potential to better mimic the
      physiological response to meals than regular human insulin. Insulin aspart when
      combined with a suitable basal insulin improved overall glycaemic control and led
      to a similar or lower number of hypoglycaemic episodes compared with a similar
      regular human insulin regimen. Insulin aspart was generally as effective and well
      tolerated as insulin lispro when administered by continuous subcutaneous infusion
      in a single comparative trial. The efficacy of biphasic insulin aspart has been
      documented in a small number of trials. Both insulin aspart and biphasic insulin
      aspart provide for flexible and convenient administration. Insulin aspart is now
      well established as an effective and convenient means of providing glycaemic
      control which offers clinical and practical advantages over regular human
      insulin.

PMID- 12215069
TI  - Valsartan/hydrochlorothiazide: a review of its pharmacology, therapeutic efficacy
      and place in the management of hypertension.
AB  - The combination of valsartan [an angiotensin II type 1 (AT(1)) receptor blocker]
      and hydrochlorothiazide (a thiazide diuretic), administered once daily, has been
      evaluated in the treatment of patients with hypertension in clinical trials
      ranging in duration from 8 weeks to 3 years. These studies showed that
      combination treatment with valsartan 80 or 160mg and hydrochlorothiazide 12.5 or
      25mg induced significant reductions from baseline in systolic blood pressure
      (SBP) and diastolic BP (DBP) in patients with mild to severe hypertension.
      Clinical trials have demonstrated that the combination of valsartan 80 or 160mg
      with hydrochlorothiazide 12.5 or 25mg is significantly more effective than either
      drug alone. Furthermore, valsartan plus hydrochlorothiazide was effective at
      reducing BP in patients unresponsive to monotherapy with either agent alone.
      Effective BP control with valsartan plus hydrochlorothiazide was maintained in
      long-term studies, with reductions observed after 3 months of treatment being
      similar to those seen after 1, 2 or 3 years. Fixed-dose
      valsartan/hydrochlorothiazide showed similar BP reductions to amlodipine and to
      valsartan plus benazepril. Valsartan/hydrochlorothiazide also provided effective
      24-hour ambulatory SBP/DBP control. Headache, dizziness and fatigue were the most
      common adverse events occurring in clinical trials; the incidence of these events
      in valsartan plus hydrochlorothiazide recipients was not significantly different
      to that in placebo recipients. Hypokalaemia occurred in 4.5% of valsartan plus
      hydrochlorothiazide recipients; valsartan attenuated the hydrochlorothiazide
      associated decrease in serum potassium concentrations. CONCLUSIONS: the
      combination of valsartan and hydrochlorothiazide is an effective treatment for
      patients with hypertension. Clinical trials have demonstrated that the
      combination is more effective than either drug alone, and is effective in
      patients not responding to monotherapy with either agent. Furthermore, the
      adverse event profile of valsartan/hydrochlorothiazide is similar to that of
      placebo. Unless there are compelling or specific indications for other drugs,
      current data support the use of valsartan/hydrochlorothiazide when patients are
      unresponsive to monotherapy with either agent. Results from clinical trials
      evaluating the effects of valsartan/hydrochlorothiazide on cardiovascular
      morbidity and mortality will help to further define the role of the combination
      in the management of hypertension.

PMID- 12215070
TI  - Grammar and lexicon in facilitated communication: a linguistic authorship
      analysis of a Finnish case.
AB  - This case study adds a new dimension to the discourse on the authorship issue in
      facilitated communication. The linguistic structure produced by a young Finnish
      man with severe cerebral palsy was examined. Data are based on transcripts he
      produced from 1993 until 1996 after facilitated communication had been introduced
      to him. In the data analysis, as explicit criteria for his idiosyncrasies, we
      used patterns typical of children acquiring Finnish as their first language and
      those found in normal slips of the tongue, acquired aphasia, and specific
      language impairment. Based on the analysis (i.e. the idiosyncrasy and
      agrammaticality of word-forms and sentences), we strongly suggest that his output
      can hardly be a product of any other speaker of Finnish, including that of his
      facilitators.

PMID- 12215071
TI  - Enhancing independent time-management skills of individuals with mental
      retardation using a Palmtop personal computer.
AB  - Achieving greater independence for individuals with mental retardation depends
      upon the acquisition of several key skills, including time-management and
      scheduling skills. The ability to perform tasks according to a schedule is
      essential to domains like independent living and employment. The use of a
      portable schedule prompting system to increase independence and self-regulation
      in time-management for individuals with mental retardation was examined. Twelve
      people with mental retardation participated in a comparison of their use of the
      technology system to perform tasks on a schedule with use of a written schedule.
      Results demonstrated the utility of a Palmtop computer with schedule prompting
      software to increase independence in the performance of vocational and daily
      living tasks by individuals with mental retardation.

PMID- 12215072
TI  - Eight-year follow-up of the impact of environmental characteristics on well-being
      of adults with developmental disabilities.
AB  - The impact of environmental features of residences on adaptive behavior,
      community integration, and health of adults with mental retardation over an 8
      year period was examined. Environmental features included residence type, size,
      choice-making opportunities, physical attractiveness, and family involvement. We
      assessed 186 residents who initially lived in nursing homes. At the 8-year follow
      up, 133 had moved to community-based residential settings. Findings indicated
      that residents who moved to community settings had higher levels of adaptive
      behavior and community integration than residents who remained in nursing homes.
      A more attractive physical environment and greater opportunity for choice-making
      were associated with higher levels of adaptive behavior at follow-up. Greater
      opportunity to make choices and family involvement were associated with higher
      levels of community integration.

PMID- 12215073
TI  - Self-determination and mental retardation: is there an association with living
      arrangement and lifestyle satisfaction?
AB  - Self-determination and lifestyle satisfaction of 80 adults with mild or medium
      mental retardation living in group homes or their parents' homes were examined.
      They were assessed in regard to self-determination, as indicated by choices made
      in the domestic, financial, health, social, and work domains. Lifestyle
      satisfaction with residence, the community, associated services, and employment
      was also assessed. Results show that those from group homes were lower on self
      determination but higher on lifestyle satisfaction, providing support for the
      commitment to normalization and community inclusion to enhance lifestyle
      satisfaction. However, questions about the extent to which people with mental
      retardation are afforded decision-making opportunities and self-determined
      behavior remain. We suggest that service providers and caregivers should
      encourage and create such opportunities.

PMID- 12215074
TI  - Integrating supports in assessment and planning.
AB  - A systematic approach for addressing the support needs of persons with mental
      retardation and related developmental disabilities is presented and a new scale
      to measure individual differences in support needs described. The process
      employed in developing the scale is explained, including the establishment of a
      typology of support areas that was drawn from a review of the professional
      literature, a validation process using Q-sort methodology, and a pilot field
      test. Critical issues and practical challenges associated with efforts to measure
      and address the support needs of individuals are discussed.

PMID- 12215075
TI  - Selected trends in public spending for MR/DD services and the state economies.
AB  - In this article we summarize mental retardation/developmental disabilities
      (MR/DD) spending since 1977, with emphasis on spending during the period 1995
      2000. The change in state economic conditions, from strong growth in recent years
      to fiscal constraint in 2002, is also addressed. Spending data presented here are
      from the seventh State of the States in Developmental Disabilities (Braddock,
      2002). Selected state-by-state information is also available at the study's
      website: http://www.cu.edu/ColemanInstitute/stateofthestates.

PMID- 12215077
TI  - Ischemic basis for deep white matter hyperintensities in major depression: a
      neuropathological study.
AB  - BACKGROUND: White matter hyperintensities on magnetic resonance imaging are
      increased in major depression in the deep white matter, especially in frontal
      areas. These lesions have been hypothesized to be ischemic in origin, but there
      have been no previous neuropathological studies in depression. We investigated
      the neuropathological basis of these lesions in depression, hypothesizing that
      they would be more frequently ischemic in origin in depressed subjects. METHODS:
      We carried out in vitro magnetic resonance imaging on 3 slices of brain tissue (2
      frontal, 1 occipital) from 20 elderly subjects who had a history of major
      depression and 20 elderly controls. The films were blindly rated, and sections
      were prepared for neuropathological analysis from the same slices and stained
      conventionally and by means of immunohistochemistry for microglia, macrophages,
      and astroglia. Lesions on the films were identified in the tissue, blindly
      described neuropathologically, and subsequently divided into ischemic and
      nonischemic lesions. RESULTS: All the deep white matter hyperintensities in the
      depressed group were found to be ischemic, compared with less than a third of
      those in the control group, a highly significant difference (P<.001). This
      difference was due to smaller punctate lesions (<3 mm), which were predominantly
      ischemic in depressed subjects but not in control subjects. Larger lesions were
      usually ischemic in both groups. Compared with control subjects, ischemic lesions
      were significantly more likely to be in the dorsolateral prefrontal cortex
      compared with the anterior cingulate cortex (P =.003) and the occipital cortex (P
      =.01) in the depressed subjects. CONCLUSIONS: Deep white matter hyperintensities
      are more frequently due to cerebral ischemia, and such ischemic lesions are more
      frequently located at the level of dorsolateral prefrontal cortex in depressed
      subjects. Our findings strongly support the "vascular depression" hypothesis of
      late-life depression.

PMID- 12215076
TI  - Fusiform gyrus volume reduction in first-episode schizophrenia: a magnetic
      resonance imaging study.
AB  - BACKGROUND: The fusiform gyrus (occipitotemporal gyrus) is thought to be critical
      for face recognition and may possibly be associated with impaired facial
      recognition and interpretation of facial expression in schizophrenia. of
      postmortem studies have suggested that fusiform gyrus volume is reduced in
      schizophrenia, but there have been no in vivo structural studies of the fusiform
      gyrus in schizophrenia using magnetic resonance imaging. METHODS: High-spatial
      resolution magnetic resonance images were used to measure the gray matter volume
      of the fusiform gyrus in 22 patients with first-episode schizophrenia (first
      hospitalization), 20 with first-episode affective psychosis (mainly manic), and
      24 control subjects. RESULTS: Patients with first-episode schizophrenia had
      overall smaller relative volumes (absolute volume/intracranial contents) of
      fusiform gyrus gray matter compared with controls (9%) and patients with
      affective psychosis (7%). For the left fusiform gyrus, patients with
      schizophrenia showed an 11% reduction compared with controls and patients with
      affective psychosis. Right fusiform gyrus volume differed in patients with
      schizophrenia only compared with controls (8%). CONCLUSION: Schizophrenia is
      associated with a bilateral reduction in fusiform gyrus gray matter volume that
      is evident at the time of first hospitalization and is different from the
      presentation of affective psychosis.

PMID- 12215078
TI  - Major depression in 6050 former drinkers: association with past alcohol
      dependence.
AB  - BACKGROUND: The association between alcoholism and major depression in the
      general population has been explained as misdiagnosed alcohol intoxication and
      withdrawal effects mistaken for depressive syndromes. To investigate whether this
      could account for the entire relationship, the association of past alcohol
      dependence with current major depression (ie, nonoverlapping time frames) was
      investigated in individuals who no longer drink or who drink very little. We
      conducted the study using data from the National Longitudinal Alcohol
      Epidemiologic Survey, a representative sample. METHODS: Former drinkers who did
      not use drugs or smoke in the past year (n = 6050) were divided into those with
      and without past DSM-IV alcohol dependence. These 2 groups were compared for the
      presence of current (last 12 months) DSM-IV major depression. The association
      between prior alcohol dependence and current major depression was tested with
      linear logistic regression, controlling for other variables. RESULTS: Prior
      alcohol dependence increased the risk of current major depressive disorder more
      than 4-fold. This relationship was not attenuated by control variables. The
      majority of subjects with major depression last used substances 2 or more years
      prior to the interview, which eliminates acute intoxication or withdrawal effects
      as an explanation of their depressions. CONCLUSIONS: The strong, specific
      association between prior alcohol dependence and current or recent major
      depression in a nationally representative sample of former drinkers indicates
      that the association is not entirely an artifact of misdiagnosed intoxication and
      withdrawal effects. A better understanding of the nature of the relationship
      between the 2 disorders should be sought and will have important public health
      significance.

PMID- 12215079
TI  - Familial pathways to early-onset suicide attempt: risk for suicidal behavior in
      offspring of mood-disordered suicide attempters.
AB  - BACKGROUND: Although adoption, twin, and family studies have shown that suicidal
      behavior is familial, the risk factors for familial transmission from parent to
      child remain unclear. METHODS: A high-risk family study was conducted comparing
      the offspring of 2 mood-disordered groups: suicide attempters and nonattempters.
      Recruited from 2 sites, probands were 81 attempters and 55 nonattempters, with
      183 and 116 offspring, respectively. Offspring were assessed by investigators
      masked to proband status. Probands and offspring were assessed with respect to
      psychopathologic findings, suicide attempt history, impulsive aggression, and
      exposure to familial environmental stressors. RESULTS: Offspring of attempters
      had a 6-fold increased risk of suicide attempts relative to offspring of
      nonattempters. Familial transmission of suicide attempt was more likely if (1)
      probands had a history of sexual abuse and (2) offspring were female and had a
      mood disorder, substance abuse disorder, increased impulsive aggression, and a
      history of sexual abuse. CONCLUSIONS: The offspring of mood-disordered suicide
      attempters are at markedly increased risk for suicide attempts themselves.
      Familial transmission of suicidal behavior in families with mood disorders almost
      always requires transmission of a mood disorder and is also related to the
      offspring's impulsive aggression and the familial transmission of sexual abuse.
      Early treatment of mood disorders and targeting impulsive aggression and sexual
      trauma may be helpful in the prevention and treatment of suicidal behavior in
      families with mood disorders.

PMID- 12215080
TI  - Visual fixation patterns during viewing of naturalistic social situations as
      predictors of social competence in individuals with autism.
AB  - BACKGROUND: Manifestations of core social deficits in autism are more pronounced
      in everyday settings than in explicit experimental tasks. To bring experimental
      measures in line with clinical observation, we report a novel method of
      quantifying atypical strategies of social monitoring in a setting that simulates
      the demands of daily experience. Enhanced ecological validity was intended to
      maximize between-group effect sizes and assess the predictive utility of
      experimental variables relative to outcome measures of social competence.
      METHODS: While viewing social scenes, eye-tracking technology measured visual
      fixations in 15 cognitively able males with autism and 15 age-, sex-, and verbal
      IQ-matched control subjects. We reliably coded fixations on 4 regions: mouth,
      eyes, body, and objects. Statistical analyses compared fixation time on regions
      of interest between groups and correlation of fixation time with outcome measures
      of social competence (ie, standardized measures of daily social adjustment and
      degree of autistic social symptoms). RESULTS: Significant between-group
      differences were obtained for all 4 regions. The best predictor of autism was
      reduced eye region fixation time. Fixation on mouths and objects was
      significantly correlated with social functioning: increased focus on mouths
      predicted improved social adjustment and less autistic social impairment, whereas
      more time on objects predicted the opposite relationship. CONCLUSIONS: When
      viewing naturalistic social situations, individuals with autism demonstrate
      abnormal patterns of social visual pursuit consistent with reduced salience of
      eyes and increased salience of mouths, bodies, and objects. Fixation times on
      mouths and objects but not on eyes are strong predictors of degree of social
      competence.

PMID- 12215081
TI  - A comparison of contingency management and cognitive-behavioral approaches during
      methadone maintenance treatment for cocaine dependence.
AB  - BACKGROUND: This study compared 2 psychosocial approaches for the treatment of
      cocaine dependence: contingency management (CM) and cognitive-behavioral therapy
      (CBT). METHODS: Patients with cocaine dependence who were receiving methadone
      maintenance treatment (n = 120) were randomly assigned to 1 of 4 conditions: CM,
      CBT, combined CM and CBT (CBT + CM), or treatment as usual (ie, methadone
      maintenance treatment program only [MMTP only]) (n = 30 per cell). The CM
      procedures and CBT materials were comparable to those used in previously
      published research. The active study period was 16 weeks, requiring 3 clinic
      visits per week. Participants were evaluated during treatment and at 17, 26, and
      52 weeks after admission. RESULTS: Urinalysis results during the 16-week
      treatment period show that participants assigned to the 2 groups featuring CM had
      significantly superior in-treatment urinalysis results, whereas urinalysis
      results from participants in the CBT group were not significantly different than
      those from the MMTP-only group. At week 17, self-reported days of cocaine use
      were significantly reduced from baseline levels for all 3 treatment groups but
      not for the MMTP-only group. At the 26-week and 52-week follow-up points, CBT
      participants showed substantial improvement, resulting in equivalent performance
      with the CM groups as indicated by both urinalysis and self-reported cocaine use
      data. CONCLUSIONS: Study findings provide solid evidence of efficacy for CM and
      CBT. Although the effect of CM is significantly greater during treatment, CBT
      appears to produce comparable long-term outcomes. There was no evidence of an
      additive effect for the 2 treatments in the CM + CBT group.

PMID- 12215082
TI  - A functional neuropeptide Y Leu7Pro polymorphism associated with alcohol
      dependence in a large population sample from the United States.
AB  - BACKGROUND: Quantitative trait locus studies, and observations in animals
      manipulated for the neuropeptide Y (NPY) gene suggest that variation within this
      gene may contribute to alcoholism. A recent population study suggested that the
      Pro7 allele of a functional NPY polymorphism (Leu7Pro) may be associated with
      increased alcohol consumption. We tested whether the Pro7 allele is associated
      with alcohol dependence in European Americans (EA). METHODS: The design was a
      population study comparing the Leu7Pro allele frequencies in alcohol-dependent
      subjects and controls. Population stratification potential and diagnostic
      specificity was studied by genotyping individuals from additional populations and
      psychiatric diagnostic classes. We studied 2 independently collected samples of
      EA alcohol-dependent subjects (sample 1, n = 307; sample 2, n = 160) and a sample
      of psychiatrically screened EA controls (n = 202); 8 population samples,
      including African Americans and European Americans (total n = 551); and 4 samples
      of individuals with Alzheimer disease, schizophrenia, posttraumatic stress
      disorder, and major depression (total n = 502). The main outcome measure was the
      difference in Leu7Pro allele frequencies between alcohol-dependent subjects and
      controls. RESULTS: The frequency of the Pro7 allele was higher in the alcohol
      dependent subjects (sample 1, 5.5%; sample 2, 5.0%) compared with the screened EA
      controls (2.0%) (sample 1 vs controls, P=.006; sample 2 vs controls, P=.03). The
      attributable fraction (excess morbidity) in similarly affected populations, owing
      to the Pro7 allele, was estimated to be 7.3%. The frequency of the Pro7 allele
      was equal or lower in the population samples, as compared with the screened EA
      controls (0%-2.2%), with 1 exception (Bedouins). We found no significant evidence
      that the association of the Pro7 allele with alcohol dependence was due to an
      association with a comorbid psychiatric disorder. CONCLUSIONS: These results
      suggest that the NPY Pro7 allele is a risk factor for alcohol dependence. This is
      only the second specific genetic mechanism ever identified that modulates risk
      for alcohol dependence.

PMID- 12215083
TI  - Autonomic response in depersonalization disorder.
AB  - BACKGROUND: Emotional-processing inhibition has been suggested as a mechanism
      underlying some of the clinical features of depersonalization and/or
      derealization. In this study, we tested the prediction that autonomic response to
      emotional stimuli would be reduced in patients with depersonalization disorder.
      METHODS: The skin conductance responses of 15 patients with chronic
      depersonalization disorder according to DSM-IV, 15 controls, and 11 individuals
      with anxiety disorders according to DSM-IV, were recorded in response to
      nonspecific elicitors (an unexpected clap and taking a sigh) and in response to
      15 randomized pictures with different emotional valences: 5 unpleasant, 5
      pleasant, and 5 neutral. RESULTS: The skin conductance response to unpleasant
      pictures was significantly reduced in patients with depersonalization disorder
      (magnitude of 0.017 micro siemens in controls and 0.103 micro siemens in patients
      with anxiety disorders; P =.01). Also, the latency of response to these stimuli
      was significantly prolonged in the group with depersonalization disorder (3.01
      seconds compared with 2.5 and 2.1 seconds in the control and anxiety groups,
      respectively; P =.02). In contrast, latency to nonspecific stimuli (clap and
      sigh) was significantly shorter in the depersonalization and anxiety groups (1.6
      seconds) than in controls (2.3 seconds) (P =.03). CONCLUSIONS: In
      depersonalization disorder, autonomic response to unpleasant stimuli is reduced.
      The fact that patients with depersonalization disorder respond earlier to a
      startling noise suggests that they are in a heightened state of alertness and
      that the reduced response to unpleasant stimuli is caused by a selective
      inhibitory mechanism on emotional processing.

PMID- 12215084
TI  - Left hippocampal volume as a vulnerability indicator for schizophrenia: a
      magnetic resonance imaging morphometric study of nonpsychotic first-degree
      relatives.
AB  - BACKGROUND: Clues to the causes of schizophrenia can be derived from studying
      first-degree relatives because they are genetically related to an ill family
      member. Abnormalities observed in nonpsychotic relatives are indicators of
      possible genetic vulnerability to illness, independent of psychosis. We tested 4
      hypotheses: (1) that hippocampal volume is smaller in nonpsychotic relatives than
      in controls, particularly in the left hemisphere; (2) that hippocampi will be
      smaller in multiplex relatives as compared with simplex relatives, and both will
      be smaller than in controls; (3) that hippocampal volumes and verbal declarative
      memory function will be positively correlated; and (4) that hippocampi will be
      smaller in patients with schizophrenia than in their nonpsychotic relatives or in
      controls. METHODS: Subjects were 45 nonpsychotic adult first-degree relatives
      from families with either 2 people ("multiplex," n = 17) or 1 person ("simplex,"
      n = 28) diagnosed with schizophrenia, 18 schizophrenic relatives, and 48 normal
      controls. Sixty contiguous 3-mm coronal, T1-weighted 3-dimensional magnetic
      resonance images of the brain were acquired on a 1.5-T magnet. Volumes of the
      total cerebrum and the hippocampus were measured. RESULTS: Compared with
      controls, relatives, particularly from multiplex families, had significantly
      smaller left hippocampi. Verbal memory and left hippocampal volumes were
      significantly and positively correlated. Within families, hippocampal volumes did
      not differ between schizophrenic patients and their nonpsychotic relatives.
      CONCLUSIONS: Results support the hypothesis that the vulnerability to
      schizophrenia includes smaller left hippocampi and verbal memory deficits.
      Findings suggest that smaller left hippocampi and verbal memory deficits are an
      expression of early neurodevelopmental compromise, reflecting the degree of
      genetic liability to schizophrenia.

PMID- 12215085
TI  - Cortical gamma-aminobutyric acid levels across the menstrual cycle in healthy
      women and those with premenstrual dysphoric disorder: a proton magnetic resonance
      spectroscopy study.
AB  - BACKGROUND: There is increasing support for the hypothesis that gonadal steroids
      involved in the regulation of the human menstrual cycle modulate gamma
      aminobutyric acid (GABA) neuronal function. This study tests the hypothesis that
      cortical GABA neuronal function, reflected in brain GABA concentrations,
      fluctuates across the menstrual cycle in healthy women and those with
      premenstrual dysphoric disorder (PMDD) and that a menstrual cycle phase-dependent
      abnormality in brain GABA concentrations in women diagnosed as having PMDD would
      reflect altered central response to circulating gonadal and neuroactive steroids.
      METHODS: Fourteen healthy menstruating women and 9 women diagnosed as having PMDD
      were recruited from a women's behavioral health research program located at a
      university-based medical center. The women underwent serial proton magnetic
      resonance spectroscopic measurements of occipital cortex GABA levels across the
      menstrual cycle (primary outcome measure) and had blood drawn for gonadal hormone
      and neurosteroid levels determined on each scan day (secondary outcome measure).
      RESULTS: There was a significant group x phase interaction with most of the
      finding explained by the reduction in cortical GABA levels during the follicular
      phase in those with PMDD compared with healthy controls. Cortical GABA levels
      declined across the menstrual cycle in healthy women, whereas women with PMDD
      experienced an increase in cortical GABA levels from the follicular phase to the
      mid luteal and late luteal phases. Significant between-group differences in the
      relationship between hormones and GABA were observed for estradiol, progesterone,
      and allopregnanolone. CONCLUSIONS: These data strongly suggest that the GABAergic
      system is substantially modulated by menstrual cycle phase in healthy women and
      those with PMDD. Furthermore, they raise the possibility of disturbances in
      cortical GABA neuronal function and modulation by neuroactive steroids as
      potentially important contributors to the pathogenesis of PMDD.

PMID- 12215086
TI  - Comparison of glaucomatous visual field defects using standard full threshold and
      Swedish interactive threshold algorithms.
AB  - OBJECTIVES: To compare the severity, size, and depth of glaucomatous visual field
      defects using standard full threshold (FT), Swedish interactive threshold
      algorithm (SITA) standard (SS), and SITA fast (SF) algorithms of the Humphrey
      perimeter. METHODS: A prospective observational case series of 77 patients with
      glaucoma performed FT, SS, and SF 30-2 white-on-white testing programs on the
      same day on 2 occasions for 1 month. The severity of defects was compared using
      the mean deviation, pattern standard deviation, Advanced Glaucoma Intervention
      Study, and Hodapp-Anderson-Parrish severity scores. The sizes of defects were
      compared using the total number of abnormal points on the pattern deviation plot
      that fit standard criteria for glaucomatous visual field defects. The depths of
      the defects were compared using the sum of the threshold values for points
      identified in the pattern deviation plot as fitting criteria for glaucomatous
      defects. RESULTS: The mean deviations were slightly better using the SS (-9.6 +/-
      7.1 dB) or the SF (-9.1 +/- 6.7 dB) algorithm compared with the FT algorithm (
      10.3 +/- 7.1 dB) (P<.005). There were no significant differences in pattern
      standard deviations between SS (8.6 +/- 4.0, P =.08) and SF (8.1 +/- 3.6, P =.19)
      compared with FT (8.3 +/- 3.3), although the pattern standard deviation was
      higher in SS fields compared with SF fields (P<.001). Advanced Glaucoma
      Intervention Study scores were slightly better when the SS (7.5 +/- 5.6) or SF
      (7.2 +/- 5.4) algorithm was used compared with the FT algorithm (8.6 +/- 5.4)
      (P<.001). The sizes of glaucomatous defects were slightly larger using the SS
      (20.9 +/- 10.7) algorithm compared with the FT algorithm (19.2 +/- 10.9) (P
      =.004) but not the SF algorithm (20.0 +/- 10.6) (P =.11). The depth of defects
      measured by the SS (220.4 +/- 108.0 dB) and SF (219.8 +/- 101.3 dB) algorithms
      was significantly shallower compared with that measured by the FT algorithm
      (152.3 +/- 79.1 dB) (P<.001). There were no significant differences in Hodapp
      Anderson-Parrish severity scores among algorithms (P =.12). CONCLUSIONS:
      Glaucomatous defects are measured significantly shallower using the new SITA
      algorithms but are approximately the same size and severity compared with FT
      measurements. Care should be taken when using threshold values to compare
      glaucomatous defects in a patient when converting from FT to SITA algorithms.

PMID- 12215088
TI  - Photodynamic therapy for choroidal hemangioma associated with serous retinal
      detachment.
AB  - OBJECTIVE: To describe the clinical findings in 3 eyes with circumscribed
      choroidal hemangioma before and after treatment with photodynamic therapy.
      PATIENTS AND METHODS: In the setting of a tertiary referral center, 2 patients
      with circumscribed, posteriorly located, choroidal hemangiomas (thicknesses 2.4
      and 2.9 mm) contiguous with the superior boundary of the optic nerve and
      accompanied by serous detachments of the sensory retina extending into the macula
      were treated with photodynamic therapy using a Zeiss diode laser (692 nm) and a
      sensitizing dye, verteporfin. A third patient with a circumscribed subfoveal
      hemangioma (3.9 mm in thickness) and a prominent serous retinal detachment was
      similarly treated. The tumors were studied with ultrasonography and fluorescein
      angiography. Visual fields were tested with Goldmann perimetry at follow-up.
      RESULTS: Following photodynamic therapy, the serous retinal detachments resolved,
      and the choroidal hemangioma in each of the 3 eyes regressed to a nonmeasurable
      thickness within 2 to 5 months. The visual acuity improved from 20/50 to 20/20,
      20/150 to 20/20, and 3/200 to 20/200 in the respective cases. Two eyes were
      treated twice. The tumors have not recurred at follow-up visits from 11 to 16
      months. Nerve fiber bundle field defects were not demonstrated with Goldmann
      field testing. CONCLUSIONS: Photodynamic therapy seems to be effective in the
      management of circumscribed choroidal hemangioma. Following photodynamic therapy,
      the choroidal hemangiomas in 3 eyes were no longer measurable by ultrasonography,
      and the accompanying serous detachments resolved with improvement in the central
      visual acuities. Nerve fiber bundle defects were not identified.

PMID- 12215087
TI  - Corneal optical aberrations and retinal image quality in patients in whom
      monofocal intraocular lenses were implanted.
AB  - OBJECTIVES: To compare retinal image quality and optical corneal aberrations in
      patients in whom monofocal polymethyl methacrylate intraocular lenses (IOLs) were
      implanted with those in healthy subjects of a similar older age (60-70 years old)
      and to use the results to suggest improved optical designs of IOLs to maximize
      retinal image quality. METHODS: A double-pass apparatus was used to measure
      retinal image quality for 3-, 4-, and 6-mm pupil diameters. Corneal aberrations
      for a 4-mm pupil were calculated by a ray-tracing technique from the elevations
      provided by corneal topography. Two groups of 20 subjects of a similar older age
      were studied: in one group, polymethyl methacrylate monofocal IOLs were
      implanted; and in a second group, healthy subjects were used as a reference.
      RESULTS: The average retinal image quality was similar in older healthy patients
      and in patients in whom IOLs were implanted, with both groups having a
      significantly worse image quality than healthy younger subjects (aged 20-30
      years). Both groups were more tolerant to defocus than younger subjects.
      CONCLUSIONS: The average retinal image quality of patients in whom IOLs were
      implanted was worse than that of healthy younger subjects despite the good
      optical quality of isolated IOLs. This apparent paradox can be understood by the
      nature of the aberration coupling in the eyes that undergo implantation. The
      ideal substitute for the natural lens is not an IOL with the best-isolated
      optical performance, but rather one designed to compensate for the aberrations of
      the cornea-a design somehow inspired by the crystalline lens of younger subjects.

PMID- 12215089
TI  - Can Swedish interactive thresholding algorithm fast perimetry be used as an
      alternative to goldmann perimetry in neuro-ophthalmic practice?
AB  - OBJECTIVE: To assess the potential role of Swedish Interactive Thresholding
      Algorithm (SITA) Fast computerized static perimetry, compared with that of
      Goldmann manual kinetic perimetry (GVF), for reliably detecting visual field
      defects in neuro-ophthalmic practice. BACKGROUND: Automated visual field testing
      is challenging in patients with poor visual acuity or severe neurological
      disease. In these patients, GVF is often the preferred visual field technique,
      but performance of this test requires a skilled technician, and this option may
      not be readily available. The recent development of the SITA family of perimetry
      has allowed for shorter automated perimetry testing time in normal subjects and
      in glaucoma patients. However, its usefulness for detecting visual field defects
      in patients with poor vision or neurological disease has not been evaluated.
      DESIGN AND METHODS: We prospectively studied 64 consecutive, neuro
      ophthalmologically impaired patients with neurologic disability of 3 or more on
      the Modified Rankin Scale, or with visual acuity of 20/200 or worse in at least
      one eye. Goldmann manual kinetic perimetry and SITA Fast results were compared
      for each eye, with special attention to reliability, test duration, and detection
      and quantification of neuro-ophthalmic visual field defects. We categorized the
      results into 1 of 9 groups based on similarities and reliabilities. Patient test
      preference was also assessed. RESULTS: Patients were separated into 2 groups,
      those with severe neurologic deficits (n = 50 eyes) and those with severe vision
      loss but mild neurologic dysfunction or none at all (n = 50 eyes). Overall, GVF
      and SITA Fast were equally reliable in 77% of eyes. Goldmann manual kinetic
      perimetry and SITA Fast showed similar visual field results in 75% of all eyes
      (70% of eyes of patients with severe neurologic deficits and 80% of eyes with
      poor vision). The mean +/- SD duration per eye was 7.97 +/- 3.2 minutes for GVF
      and 5.43 +/- 1.41 minutes for SITA Fast (P<.001). Ninety-one percent of patients
      preferred GVF to SITA Fast. CONCLUSIONS: We found the SITA Fast strategy of
      automated perimetry to be useful in the detection, and accurate in the
      quantification of central visual field defects associated with neuro-ophthalmic
      disorders. Our results suggest that for the general ophthalmologist or
      neurologist, visual field testing with SITA Fast perimetry might even be
      preferable to GVF, especially if performed by a marginally trained technician,
      even in patients with severely decreased vision or who are neurologically
      disabled.

PMID- 12215090
TI  - Dissociated vertical divergence: perceptual correlates of the human dorsal light
      reflex.
AB  - BACKGROUND: Dissociated vertical divergence (DVD) has been attributed to a human
      dorsal light reflex that emerges when single binocular vision is precluded in
      infancy. If this is the case, then DVD should be associated with a subjective
      sensation of tilt. METHODS: Prospective examination of 9 patients with DVD and 9
      control subjects to determine whether monocular occlusion and alternate occlusion
      induces a subjective sensation of visual tilt or body tilt. RESULTS: Alternate
      occlusion disclosed a tilt in the subjective visual vertical in 8 of the 9
      patients with DVD and in none of 9 control subjects. On occlusion of the fixating
      eye, a vertical pencil positioned in the sagittal plane was perceived as
      instantaneously tilted, with its upper pole tipped toward the side of the covered
      eye. This visual tilt was quickly followed by a perceived rotation back to
      vertical, which coincided with the dorsally directed drift of the covered eye.
      CONCLUSION: In patients with DVD, monocular occlusion is associated with a
      subjective visual tilt that is annulled by a cyclovertical divergence movement of
      the eyes. This observation supports the notion that DVD is a human dorsal light
      reflex, which functions to restore vertical visual orientation when unequal
      binocular visual input evokes a subjective sensation of visual tilt.

PMID- 12215091
TI  - Docetaxel secretion in tears: association with lacrimal drainage obstruction.
AB  - OBJECTIVE: To test the hypothesis that docetaxel may be secreted in tears after
      intravenous infusion. DESIGN: Prospective pilot trial. PATIENTS AND METHODS: Tear
      fluid was collected from 4 patients receiving docetaxel weekly and 2 patients
      receiving docetaxel every 3 weeks as a single agent for the treatment of
      metastatic breast cancer. Tear samples were collected once prior to and again
      within 30 minutes following the end of the 1-hour docetaxel infusion. A blood
      sample was also obtained after infusion. The tear and plasma samples were
      analyzed for drug content using high-performance liquid chromatography and tandem
      mass spectrometry. RESULTS: Docetaxel was found in the tear samples collected
      from all 6 patients. CONCLUSION: The secretion of docetaxel in tears may be a
      mechanism for canalicular inflammation and tear drainage obstruction, which are
      known to occur as an adverse effect of the drug.

PMID- 12215092
TI  - A relationship between varicella-zoster virus-specific delayed hypersensitivity
      and varicella-zoster virus-induced anterior uveitis.
AB  - BACKGROUND: We recently reported that acute retinal necrosis in humans develops
      in a setting where delayed hypersensitivity (DH) to the varicella-zoster virus
      (VZV) antigen was absent, implying that virus-specific DH mitigates against acute
      retinal necrosis. OBJECTIVE: To determine whether a similar correlation exists
      for patients with anterior uveitis caused by VZV. DESIGN: Using VZV and purified
      protein derivative (PPD) antigens to evaluate DH, we skin tested patients with
      acute, VZV-induced anterior uveitis (herpes zoster ophthalmicus [ZO-AU]) (n =
      12), those with uveitis caused by VZV in the absence of dermatitis (zoster sine
      herpete [ZSH-AU]) (n = 3), and age-matched patients whose ophthalmic herpes
      zoster was unassociated with uveitis as controls (n = 7). Varicella-zoster virus
      induced anterior uveitis was diagnosed by polymerase chain reaction methods and
      serum antibody titration. Serum samples were collected and analyzed for anti-VZV
      antibody titers. Anterior uveitis activity was assessed clinically. Delayed
      hypersensitivity skin tests were repeated in patients with zoster sine herpete 3
      months after onset, when ocular recovery had taken place. RESULTS: All patients
      with VZV-induced skin disease alone (control group) displayed intense DH when
      tested with VZV and PPD antigens. By contrast, only 4 (33%) of 12 patients with
      ZO-AU had a positive DH to VZV, whereas 11 (91.6%) of these patients displayed
      positive PPD skin reactions. The clinical intensity of anterior uveitis
      correlated negatively with VZV DH responses (P<.05). Serum anti-VZV and anti
      herpes simplex virus antibody titers were comparable in DH-positive VZV cases and
      in DH-negative patients with uveitis. Patients with uveitis and ZSH-AU also
      displayed absent VZV-specific DH, although their PPD responses were normal. MAIN
      OUTCOME MEASURES: Varicella-zoster virus-specific DH, PPD-specific DH, VZV
      specific antibody titration, and intraocular pressure in patients with ZO-AU.
      CONCLUSIONS: Absence (or loss) of DH reactivity to VZV antigens seems to be a
      concomitant feature of VZV uveitis of high intensity, implying that virus
      specific DH may interfere with the emergence of VZV-induced anterior uveitis, as
      it does for acute retinal necrosis. CLINICAL RELEVANCE: In a clinical setting,
      absence of virus-specific DH to anterior uveitis caused by VZV may not only
      reveal a possible pathogenic mechanism, but a negative DH response may prove
      useful in diagnosing ZSH-AU in the acute stage.

PMID- 12215093
TI  - Variations in the myocilin gene in patients with open-angle glaucoma.
AB  - OBJECTIVE: To determine the prevalence and associated phenotype of myocilin
      (MYOC) coding sequence variations and a specific promoter polymorphism (MYOC.mt1)
      in patients with glaucoma and glaucoma suspects. METHODS: A consecutive,
      unselected series of 779 patients (652 with open-angle glaucoma and 127 glaucoma
      suspects) were recruited from a university medical center and clinically
      characterized. The coding sequences of the MYOC gene and the MYOC.mt1 locus in
      the promoter region were screened for sequence variations. We determined the
      prevalence of MYOC coding sequence mutations and the MYOC.mt1 promoter
      polymorphism. We also compared the clinical features of individuals with and
      without mutations and the MYOC.mt1 promoter polymorphism. RESULTS: Plausible
      disease-causing sequence variations (DCVs) in the MYOC gene were found in 3.0% of
      the entire group. Such variations were found in patients with most forms of open
      angle glaucoma studied. Patients with primary open-angle glaucoma (POAG) who
      harbored coding sequence DCVs were clinically similar to patients without them.
      Patients who harbored the rarer allele of the MYOC.mt1 promoter polymorphism were
      no different in any measure of disease severity from those who harbored the more
      common allele. CONCLUSIONS: MYOC DCVs were found in approximately 3% of patients
      with glaucoma and glaucoma suspects. The 2 alleles of the MYOC.mt1 promoter
      polymorphism were equally distributed among patients with POAG and healthy
      control subjects. Patients with POAG who harbored the rarer allele of the
      MYOC.mt1 promoter polymorphism were no different from those with the more common
      variant in any measure of disease severity. CLINICAL RELEVANCE: Testing for the
      MYOC.mt1 promoter polymorphism appears to be of no value in the evaluation of
      patients with glaucoma.

PMID- 12215094
TI  - Sir Nicholas Harold Ridley, Kt, MD, FRCS, FRS: contributions in addition to the
      intraocular lens.

PMID- 12215095
TI  - When does information become medically useful?: the role of genetic testing in
      glaucoma.

PMID- 12215096
TI  - Intravascular drug delivery with a pulsed liquid microjet.
AB  - Occlusions of the retinal veins and arteries, associated with diseases such as
      hypertension and arteriosclerosis, are a major cause of severe and irreversible
      loss of vision. Treatments for retinal vascular diseases have been unsatisfactory
      owing in part to the difficulty of delivering drugs to the site of disease within
      the eye. In this article, we demonstrate that a new device, the vapor bubble
      driven pulsed liquid microjet, can deliver drugs into the lumen of small vessels
      such as those found in the retina. A 15- micro m-diameter liquid jet traveling at
      more than 60 m/s was shown to penetrate and deliver fluid through the wall of a
      blood vessel that was 60 micro m in diameter. Perforation of the wall of the
      blood vessel did not extend beyond the jet diameter.

PMID- 12215097
TI  - Branch retinal artery occlusion caused by an embolus of metastatic gastric
      adenocarcinoma.

PMID- 12215098
TI  - Discoloration of intraocular lens subsequent to rifabutin use.

PMID- 12215099
TI  - Delayed luxation of a lens nucleus after vitrectomy.

PMID- 12215100
TI  - Refractive, topographic, and visual effects of flap amputation following laser in
      situ keratomileusis.

PMID- 12215101
TI  - Intravitreous triamcinolone acetonide as treatment for macular edema from central
      retinal vein occlusion.

PMID- 12215102
TI  - Intravitreal antivirals in the management of patients with acquired
      immunodeficiency syndrome with progressive outer retinal necrosis.

PMID- 12215103
TI  - Atypical retinoblastoma presentations: a challenge for the treating
      ophthalmologist.

PMID- 12215104
TI  - Immunotherapy for low-grade non-hodgkin secondary lymphoma of the orbit.

PMID- 12215105
TI  - Rapid growth of retinoblastoma in a premature twin.

PMID- 12215106
TI  - Screening for retinopathy of prematurity using wide-field digital retinal
      imaging: sensitivity and specificity.

PMID- 12215107
TI  - Intravenous recombinant tissue-type plasminogen activator thrombolysis in
      treatment of central retinal artery occlusion.

PMID- 12215108
TI  - Epidemiological characteristics of ocular trauma in the US Army.

PMID- 12215110
TI  - A piece of my mind. Beyond hope?

PMID- 12215111
TI  - Researchers probe health consequences following the World Trade Center attack.

PMID- 12215112
TI  - Out of tragedy, identification innovation.

PMID- 12215113
TI  - "World class" physicians get first US-Israeli training.

PMID- 12215114
TI  - From the Food and Drug Administration.

PMID- 12215122
TI  - Clinical diagnosis of urinary tract infection.

PMID- 12215123
TI  - Clinical diagnosis of urinary tract infection.

PMID- 12215125
TI  - Therapeutic footwear in patients with diabetes.

PMID- 12215126
TI  - Therapeutic footwear in patients with diabetes.

PMID- 12215128
TI  - State mandates for preventive health services.

PMID- 12215129
TI  - Rapid assessment of mortality and malnutrition in Afghanistan.

PMID- 12215130
TI  - Nationwide longitudinal study of psychological responses to September 11.
AB  - CONTEXT: The September 11, 2001, attacks against the United States provide a
      unique opportunity to examine longitudinally the process of adjustment to a
      traumatic event on a national scale. OBJECTIVE: To examine the degree to which
      demographic factors, mental and physical health history, lifetime exposure to
      stressful events, September 11-related experiences, and coping strategies used
      shortly after the attacks predict psychological outcomes over time. DESIGN,
      SETTING, AND PARTICIPANTS: A national probability sample of 3496 adults received
      a Web-based survey; 2729 individuals (78% participation rate) completed it
      between 9 and 23 days (75% within 9 to 14 days) after the terrorist attacks. A
      random sample of 1069 panelists residing outside New York, NY, were drawn from
      the wave 1 sample (n = 2729) and received a second survey; 933 (87% participation
      rate) completed it approximately 2 months following the attacks. A third survey
      (n = 787) was completed approximately 6 months after the attacks. MAIN OUTCOME
      MEASURES: September 11-related symptoms of acute stress, posttraumatic stress,
      and global distress. RESULTS: Seventeen percent of the US population outside of
      New York City reported symptoms of September 11-related posttraumatic stress 2
      months after the attacks; 5.8% did so at 6 months. High levels of posttraumatic
      stress symptoms were associated with female sex (odds ratio [OR], 1.64; 95%
      confidence interval [CI], 1.17-2.31), marital separation (OR, 2.55; 95% CI, 1.06
      6.14), pre-September 11 physician-diagnosed depression or anxiety disorder (OR,
      1.84; 95% CI, 1.33-2.56) or physical illness (OR, 0.93; 95% CI, 0.88-0.99),
      severity of exposure to the attacks (OR, 1.31; 95% CI, 1.11-1.55), and early
      disengagement from coping efforts (eg, giving up: OR, 1.68; 95% CI, 1.27-2.20;
      denial: OR, 1.33; 95% CI, 1.07-1.64; and self-distraction: OR, 1.31; 95% CI, 1.07
      1.59). In addition to demographic and pre-September 11 health variables, global
      distress was associated with severity of loss due to the attacks (beta =.07; P
      =.008) and early coping strategies (eg, increased with denial: beta =.08; P
      =.005; and giving up: beta =.05; P =.04; and decreased with active coping: beta =
      -.08; P =.002). CONCLUSIONS: The psychological effects of a major national trauma
      are not limited to those who experience it directly, and the degree of response
      is not predicted simply by objective measures of exposure to or loss from the
      trauma. Instead, use of specific coping strategies shortly after an event is
      associated with symptoms over time. In particular, disengaging from coping
      efforts can signal the likelihood of psychological difficulties up to 6 months
      after a trauma.

PMID- 12215131
TI  - Splinting vs surgery in the treatment of carpal tunnel syndrome: a randomized
      controlled trial.
AB  - CONTEXT: Carpal tunnel syndrome (CTS) can be treated with nonsurgical or surgical
      options. However, there is no consensus on the most effective method of
      treatment. OBJECTIVE: To compare the short-term and long-term efficacy of
      splinting and surgery for relieving the symptoms of CTS. DESIGN, SETTING, AND
      PATIENTS: A randomized controlled trial conducted from October 1998 to April 2000
      at 13 neurological outpatient clinics in the Netherlands. A total of 176 patients
      with clinically and electrophysiologically confirmed idiopathic CTS were assigned
      to wrist splinting during the night for at least 6 weeks (89 patients) or open
      carpal tunnel release (87 patients); 147 patients (84%) completed the final
      follow-up assessment 18 months after randomization. MAIN OUTCOME MEASURES:
      General improvement, number of nights waking up due to symptoms, and severity of
      symptoms. RESULTS: In the intention-to-treat analyses, surgery was more effective
      than splinting on all outcome measures. The success rates (based on general
      improvement) after 3 months were 80% for the surgery group (62/78 patients) vs
      54% for the splinting group (46/86 patients), which is a difference of 26% (95%
      confidence interval [CI], 12%-40%; P<.001). After 18 months, the success rates
      increased to 90% for the surgery group (61/68 patients) vs 75% for the splinting
      group (59/79 patients), which is a difference of 15% (95% CI, 3%-27%; P =.02).
      However, by that time 41% of patients (32/79) in the splint group had also
      received the surgery treatment. CONCLUSION: Treatment with open carpal tunnel
      release surgery resulted in better outcomes than treatment with wrist splinting
      for patients with CTS.

PMID- 12215133
TI  - Impact of over-the-counter sales on effectiveness of pharmaceutical aids for
      smoking cessation.
AB  - CONTEXT: Successful smoking cessation is a major public health goal. In
      controlled clinical trials, nicotine replacement therapy (NRT) and the
      antidepressant bupropion have been shown to significantly increase cessation
      rates only for moderate to heavy smokers (> or = 15 cigarettes/d). Nicotine
      replacement therapy is heavily promoted to the general population by both the
      pharmaceutical industry and tobacco control advocates. OBJECTIVE: To examine
      trends in smoking cessation, pharmaceutical cessation aid use, and success in
      cessation in the general California population. DESIGN, SETTING, AND
      PARTICIPANTS: The large population-based California Tobacco Surveys of 1992,
      1996, and 1999, including 5247 (71.3% response rate), 9725 (72.9% response rate),
      and 6412 (68.4% response rate) respondents, respectively. MAIN OUTCOME MEASURES:
      Rates of cessation attempts (> or = 1 day) among smokers in the last year, use of
      pharmaceutical aids (mostly over-the-counter products since 1996), and cessation
      success. RESULTS: Between 1992 and 1999, cessation attempts among California
      smokers increased 61.4% (from 38.1% to 61.5%), and NRT use among quitters
      increased 50.5% (from 9.3% to 14.0%). A total of 17.2% of quitters used NRT, an
      antidepressant, or both as an aid to cessation in 1999. In 1996 and 1999, the
      median duration of aid use (14 days) was much less than recommended, and only
      about 20% of users had adjuvant one-on-one or group behavioral counseling. Use of
      NRT increased short-term cessation success in moderate to heavy smokers in each
      survey year. However, a long-term cessation advantage was only observed before
      NRT became widely available over-the-counter (August 1996). In 1999, no advantage
      for pharmaceutical aid users was observed in either the short or long term for
      the nearly 60% of California smokers classified as light smokers (<15
      cigarettes/d). CONCLUSION: Since becoming available over the counter, NRT appears
      no longer effective in increasing long-term successful cessation in California
      smokers.

PMID- 12215132
TI  - Plasma natriuretic peptides for community screening for left ventricular
      hypertrophy and systolic dysfunction: the Framingham heart study.
AB  - CONTEXT: Several reports have suggested the usefulness of plasma brain
      natriuretic peptide (BNP) as a screening test for left ventricular hypertrophy
      (LVH) and systolic dysfunction (LVSD). Prior studies were limited by small sample
      sizes and selection bias and none compared the diagnostic performance of these
      peptides in men and women. OBJECTIVES: To examine the usefulness of natriuretic
      peptides for screening for elevated LV mass and LVSD in the community. DESIGN,
      SETTING, AND PARTICIPANTS: Community-based prospective cohort study of 3177
      participants (1707 women) from the Framingham Study who attended a routine
      examination in 1995-1998. MAIN OUTCOME MEASURES: Receiver operating
      characteristic (ROC) curves, test sensitivity, specificity, positive and negative
      predictive values, and likelihood ratios for identifying elevated LV mass (sex
      specific 90th percentile or higher of LV mass/[height](2)), LVSD (ejection
      fraction < or = 50% and/or fractional shortening <29%), and moderate to severe
      LVSD (ejection fraction < or = 40% and/or fractional shortening <22%) at
      different discrimination limits of plasma BNP and N-terminal proatrial
      natriuretic peptide (NT-ANP), with echocardiography as the criterion standard.
      RESULTS: The areas under the ROC curves for elevated LV mass or LVSD were at or
      below 0.75 for both peptides, were higher for men compared with women, and were
      similar for BNP and NT-ANP. The diagnostic performance of natriuretic peptides
      for LVSD improved in women but not in men when select high-risk subgroups were
      targeted. Discrimination limits based on high specificity (0.95) yielded better
      positive predictive values and likelihood ratios compared with age- and sex
      specific reference limits yet only identified less than one third of participants
      who had elevated LV mass or LVSD. CONCLUSION: In our large community-based
      sample, the performance of BNP and NT-ANP for detection of elevated LV mass and
      LVSD was suboptimal, suggesting limited usefulness of natriuretic peptides as
      mass screening tools.

PMID- 12215134
TI  - Obesity among adults with disabling conditions.
AB  - CONTEXT: Obesity, a leading cause of preventable death and chronic disease, is
      associated with disability. Little is known about obesity among adults with
      specific disabilities. OBJECTIVES: To determine the prevalence of obesity in
      adults with physical and sensory limitations and serious mental illness. DESIGN,
      SETTING, AND PARTICIPANTS: The 1994-1995 National Health Interview Survey of 145
      007 US community-dwelling respondents, 25 626 of whom had 1 or more disabilities.
      MAIN OUTCOME MEASURES: Likelihood of being obese, attempting weight loss, and
      receiving exercise counseling among adults with and without disabilities.
      RESULTS: Among adults with disabilities, 24.9% were obese vs 15.1% of those
      without disabilities. After adjusting for sociodemographic factors, adults with a
      disability were more likely to be obese, with an adjusted odds ratio (AOR) of 1.9
      (95% confidence interval [CI], 1.8-2.0). The highest risk occurred among adults
      with some (AOR, 2.4; 95% CI, 2.3-2.5) or severe (AOR, 2.5; 95% CI, 2.3-2.7) lower
      extremity mobility difficulties. After further adjustment for comorbid
      conditions, adults with disabilities were as likely to attempt weight loss as
      those without disabilities, except for adults with severe lower extremity
      mobility difficulties, who were less likely (AOR, 0.7; 95% CI, 0.5-0.9]), and
      adults with mental illness, who were more likely (AOR, 1.4; 95% CI, 1.2-1.8).
      Physician exercise counseling was reported less often among adults with severe
      lower extremity (AOR, 0.5; 95% CI, 0.4-0.7) and upper extremity (AOR, 0.7; 95%
      CI, 0.5-1.0) mobility difficulties. CONCLUSION: Obesity appears to be more
      prevalent in adults with sensory, physical, and mental health conditions. Health
      care practitioners should address weight control and exercise among adults with
      disabilities.

PMID- 12215135
TI  - Adolescent grief: "It never really hit me...until it actually happened".
AB  - In the United States, more than 2 million children and adolescents (3.4%) younger
      than 18 years have experienced the death of a parent. When death can be
      anticipated, as with a terminal illness, and even when the death is sudden, as in
      the September 11, 2001, attacks on the World Trade Center and Pentagon,
      physicians and other health care professionals have an opportunity to ameliorate
      the impact of the loss. Developmental factors shape adolescents' reactions and
      responses to the death of a parent. Recent research in childhood and adolescent
      bereavement shows how health professionals can support the adolescent's coping
      strategies and prepare the family to facilitate an adolescent's mastery of
      adaptive tasks posed by the terminal phase of the parent's illness, the death,
      and its aftermath. Robert, a bereaved 14-year-old, illustrates some of these
      adaptive challenges.

PMID- 12215136
TI  - Reflections at a palliative care unit.

PMID- 12215137
TI  - Heroism.

PMID- 12215138
TI  - Treatment options for carpal tunnel syndrome.

PMID- 12215146
TI  - Department of Surgery, the University of Hong Kong.

PMID- 12215139
TI  - Maternal mortality in Herat Province, Afghanistan, in 2002: an indicator of
      women's human rights.
AB  - CONTEXT: Maternal mortality rates in Afghanistan are estimated to be high.
      OBJECTIVE: To assess maternal mortality and human rights issues in Herat,
      Afghanistan. DESIGN AND SETTING: Cross-sectional survey of 4886 Afghan women
      living in 7 districts in Afghanistan's Herat Province, which included 34 urban
      and rural villages/towns. Using structured interviews/questionnaires, these women
      also provided maternal mortality information on 14 085 sisters in March 2002. A
      survey of health facilities in the 7 districts was also conducted. PARTICIPANTS:
      Mean (SE) age of the respondents was 31 (0.23) years (range, 15-49 years). The
      majority had received 0.35 (0.11) years of formal education and 4233 (88%) were
      married (mean [SE] age at marriage, 15 [0.3] years; range, 5-39 years). The mean
      (SE) number of pregnancies was 5.0 (0.08) and live births was 4.6 (0.2). RESULTS:
      There were 276 maternal deaths among 14 085 sisters of the survey respondents
      (593 maternal deaths/100 000 live births per year; 95% confidence interval [CI],
      557-630). Of the 276 deaths, 254 (92%) were reported from rural areas. The
      respondents reported the following primary problems: lack of food (41%), shelter
      (18%), and clean water (14%). Of 4721 respondents, 4008 (85%) wanted to get
      married at the time of their wedding, but 957 (20%) felt family pressure. Of 4703
      women, 4117 (87%) had to obtain permission from their husband or male relative to
      seek health care; only 1% (54/3946) reported not being permitted to obtain
      prenatal care. Of 4881 women, 597 (12%) used birth control, but 23% (1013/4294)
      wanted to use birth control. Of 4306 women, 3189 (74%) reported that decisions
      about the number and spacing of children were made by husband and wife equally.
      Of 4637 respondents, 519 (11%) reported receiving prenatal care. Of 4624 women,
      40 (0.9%) reported a trained health care worker was present at birth; 97%
      (4475/4612) had untrained traditional birth attendants. Only 17 of 27 listed
      health facilities were functional and only 5 provided essential obstetric care.
      Only 35 physicians served a population of 793 214. CONCLUSIONS: Women in most of
      Herat Province, Afghanistan, have a high risk of maternal mortality. Human rights
      factors may contribute to preventable maternal deaths in the region.

PMID- 12215147
TI  - Outcome of elderly patients with appendicitis: effect of computed tomography and
      laparoscopy.
AB  - HYPOTHESIS: Elderly patients who have appendicitis have a greater morbidity and
      mortality rate when compared with younger patients. We hypothesized that recent
      changes in the diagnosis and management of appendicitis in elderly patients might
      affect the outcome. DESIGN: Retrospective review. SETTING: Large metropolitan
      teaching hospital. PATIENTS: All patients aged 70 years and older who underwent
      appendectomy for appendicitis between January 1, 1991, and December 31, 2000,
      were divided into groups 1 (those treated from January 1, 1991, through December
      31, 1995) and 2 (those treated from January 1, 1996, through December 31, 2000).
      MAIN OUTCOME MEASURES: Age, sex, preoperative evaluation, operative duration and
      findings, postoperative course, duration of hospital stay, and mortality rate.
      Continuous and categorical variables were analyzed using t and chi(2) tests,
      respectively. RESULTS: Ninety-five patients met inclusionary criteria. The mean
      age (78 years), sex, preoperative suggestion of appendicitis (group 1, 39 [83%]
      of 47 patients; group 2, 45 [94%] of 48 patients), and duration of the
      preoperative hospitalization over 24 hours (group 1, 11 patients [23%]; group 2,
      9 patients [19%]) were similar in both groups. There was an increasing use of
      diagnostic computed tomography (group 1, 13 patients [28%]; group 2, 32 patients
      [67%]; P<.001) and laparoscopy (group 1, 14 patients [30%]; group 2, 23 patients
      [48%]; P =.02) between the 2 study periods associated with no significant
      difference in the duration of hospitalization, frequency of appendiceal
      perforation or abscess, occurrence of complications, or mortality. The length of
      operating time increased in the second period (ie, January 1, 1996, through
      December 31, 2000). CONCLUSIONS: Appendicitis in elderly patients continues to be
      a challenging surgical problem. While computed tomography may represent a useful
      diagnostic tool and laparoscopic appendectomy may be appropriate therapy for
      selected patients, neither has affected outcome when measured for morbidity and
      mortality rates. Overall results might improve with earlier consideration of the
      diagnosis in elderly patients with abdominal pain, followed by prompt surgical
      consultation and operation.

PMID- 12215149
TI  - Positron emission tomography in the initial staging of esophageal cancer.
AB  - OBJECTIVE: To assess the value of positron emission tomography (PET) compared
      with computed tomography (CT) in the initial staging of esophageal cancer.
      DESIGN: Case series. SETTING: Tertiary care veterans hospital. PATIENTS: Patients
      with newly diagnosed esophageal cancers from January 1996 through May 2001 who
      underwent both CT and PET scanning within 4 weeks were included in the study (n =
      24). Only patients who underwent pathological or radiographic follow-up were
      included. MAIN OUTCOME MEASURES: The sensitivity, specificity, and negative and
      positive predictive values of CT and PET were determined based on a criterion
      standard of pathological staging in 16 patients (67%) and follow-up imaging in 8
      patients (33%). RESULTS: For staging regional lymph node involvement, CT and PET
      scans showed no statistically significant difference in sensitivity (57% and 71%,
      respectively) and specificity (71% and 86%, respectively). For detection of
      metastatic disease, CT and PET showed no significant difference in sensitivity
      (83% and 67%, respectively) and specificity (75% and 92%, respectively). There
      was no significant difference in clinical decision making when the results of
      both tests were discordant. CONCLUSIONS: There was no significant difference
      between the 2 imaging modalities in the initial staging of esophageal cancer. The
      CT scan was a sensitive indicator of distant metastases, whereas PET was more
      specific. It is unclear what additional role PET scanning should have in the
      initial screening of patients.

PMID- 12215150
TI  - Postoperative symptoms and failure after antireflux surgery.
AB  - BACKGROUND: Outcomes in patients having surgery for gastroesophageal reflux
      disease are most commonly determined by symptomatic assessment. Objective testing
      is usually reserved for symptomatic patients. HYPOTHESIS: To evaluate the
      relationship between symptomatic and objective outcomes after antireflux surgery.
      DESIGN: Retrospective analysis of prospectively collected data. SETTING: A
      tertiary care teaching hospital with a comprehensive esophageal physiology
      laboratory. INTERVENTIONS: A 360 degrees (Nissen) fundoplication or a 270 degrees
      (Toupet) posterior fundoplication was performed based on esophageal motility.
      Twenty-four-hour pH monitoring was used as a gold standard for assessing
      postoperative acid reflux. PATIENTS: Two hundred nine consecutive patients with
      preoperative and postoperative symptomatic and objective testing performed
      between January 1, 1996, and June 15, 2001. MAIN OUTCOME MEASURES: Data on
      preoperative and postoperative symptoms, DeMeester scores, and esophageal
      motility were prospectively collected. Objective testing was performed after at
      least 6 months. RESULTS: The preoperative median DeMeester score was 50.0
      (interquartile [IQ] range, 30.3-87.0). One hundred eighty patients had a Nissen
      and 29 patients had a Toupet fundoplication. After a median postoperative
      interval of 7.7 months (IQ range, 6.7-9.5 months), 174 patients (83.3%) had
      normal DeMeester scores (median, 2.2; IQ range, 0.8-5.0; P<.001). Of 58 patients
      (27.7%) who had reflux symptoms after surgery, only 17 (29.3%) had abnormal
      DeMeester scores (median, 36.9; IQ range, 748.4-20.0; P =.001). Eighteen (11.9%)
      of the 151 asymptomatic patients had abnormal DeMeester scores (median, 32.5; IQ
      range, 22.2-57.5; P =.006). CONCLUSIONS: There is poor correlation between
      postoperative reflux symptoms and actual reflux (abnormal DeMeester scores).
      Surgeons must be careful to define their terms when reporting success or failure
      rates after antireflux surgery. Routine use of medical therapy for suppressing
      postoperative gastroesophageal reflux disease symptoms is not supported by these
      data, and postoperative therapy should be based on objective testing only.

PMID- 12215151
TI  - The impact of hormone replacement therapy on the detection and stage of breast
      cancer.
AB  - HYPOTHESIS: Patients who receive hormone replacement therapy (HRT) and
      subsequently develop breast cancer are more likely to be diagnosed by palpation
      than mammography and have a higher stage of cancer at initial diagnosis. DESIGN:
      Retrospective case series. SETTING: University hospital. PATIENTS: Two hundred
      ninety-two patients with breast cancer who were postmenopausal. INTERVENTIONS:
      Clinical examination, mammography, and definitive therapy. MAIN OUTCOME MEASURES:
      Hormone replacement therapy use, mode of cancer detection, tumor size, nodal
      status, stage, and survival. RESULTS: Patients receiving HRT prior to diagnosis
      had significantly more incidences of mammographically detected tumors, ductal
      carcinoma in situ, T1 lesions, negative nodes, and better survival rates than
      nonusers. CONCLUSIONS: A history of HRT use had only beneficial and no
      discernible adverse effects on breast cancer detection and outcomes. These
      effects of HRT seem to be due to the development of less aggressive tumors rather
      than earlier detection.

PMID- 12215152
TI  - Surgical treatment of hyperparathyroidism improves health-related quality of
      life.
AB  - HYPOTHESIS: The surgical treatment of primary hyperparathyroidism results in an
      improved health-related quality of life. DESIGN: Prospective cohort analysis of
      consecutive patients with primary hyperparathyroidism analyzed preoperatively and
      1 year postoperatively. SETTING: Academic multispecialty referral clinic.
      PATIENTS: We prospectively evaluated 74 consecutive patients who underwent
      parathyroid exploration for primary hyperparathyroidism during a 15-month period.
      INTERVENTIONS: The Medical Outcomes Study Short-Form Health Survey (SF-36) was
      administered before consultation with a surgeon. Patients were categorized based
      on reason for referral as either asymptomatic (group 1; n = 43) or symptomatic
      (group 2; n = 29). All patients underwent parathyroid exploration and
      normalization of calcium levels postoperatively. The SF-36 was then re
      administered after 1 year. MAIN OUTCOME MEASURES: Statistical analysis of
      preoperative and postoperative SF-36 scores, and comparisons with national norms.
      RESULTS: The SF-36 was completed preoperatively and 1 year postoperatively by 72
      (97%) of 74 patients. When the results were compared with published national
      norms, the preoperative population was significantly impaired in 5 of 8 domains,
      whereas the postoperative one had improved and was nearly indistinguishable from
      the norm. In 7 of 8 domains, the postoperative scores were significantly improved
      compared with preoperative scores. Group 1 patients showed significant
      preoperative impairment in 3 domains and significantly improved in 2, whereas
      group 2 patients showed significant impairment and improvement in 7 domains.
      CONCLUSION: The surgical treatment of primary hyperparathyroidism is associated
      with durable, statistically significant improvements in health-related quality of
      life.

PMID- 12215153
TI  - Defining the role of computed tomography in blunt abdominal trauma: use in the
      hemodynamically stable patient with a depressed level of consciousness.
AB  - HYPOTHESIS: Controversy exists regarding the use of diagnostic peritoneal lavage
      (DPL) vs computed tomography (CT) in the evaluation of blunt abdominal trauma. It
      has been suggested that one role for DPL is to diagnose bowel injuries in
      hemodynamically stable patients with an unreliable abdominal examination result.
      Our hypothesis is that CT is specific and sensitive for diagnosing hollow viscus
      injuries and is therefore an appropriate diagnostic modality in the
      hemodynamically stable blunt trauma patient with an unreliable abdominal
      examination result due to a depressed level of consciousness. DESIGN:
      Retrospective consecutive case review. SETTING: An urban level II trauma center.
      PATIENTS: The medical records of 1388 consecutive patients admitted between
      January 1, 1991, and December 31, 2000, were reviewed. Inclusion criteria
      included blunt trauma patients who were hemodynamically stable (defined as a
      systolic blood pressure >90 mm Hg) with unreliable abdominal examination results
      secondary to a depressed level of consciousness (Glasgow Coma Scale score <11).
      MAIN OUTCOME MEASURES: Hollow viscus injury diagnosed by CT and missed diagnosis
      of hollow viscus injury by CT. RESULTS: Of 1388 patients who met entry criteria,
      87 had hollow viscus injuries; CT identified 85 of these injuries. Computed
      tomography diagnosed intestinal injury with a sensitivity of 97.7%, specificity
      of 98.5%, and an overall accuracy of 99.4%. CONCLUSION: At our institution, CT is
      a reliable and accurate diagnostic modality when used to evaluate hollow viscus
      injuries in the hemodynamically stable blunt trauma patient with an unreliable
      abdominal examination result due to a depressed level of consciousness.

PMID- 12215154
TI  - Kaiser, Garfield, and Permanente.
AB  - Henry J. Kaiser developed an extensive and complex industrial empire. During the
      construction of the Grand Coulee Dam in Washington, he began an association with
      Sidney Garfield, MD, that resulted in the prototype of the modern health
      maintenance organization. Kaiser Permanente, directed by Garfield, survived a
      confrontation with organized medicine in the postwar years and then expanded
      rapidly in the 1950s and 1960s. At the same time, an internal struggle for
      control and responsibility of Kaiser Permanente led to a successful
      reorganization of its health care system. Today, Kaiser Permanente is Henry
      Kaiser's most enduring legacy.

PMID- 12215155
TI  - Decreased cytokine expression in peripheral blood leukocytes of patients with
      severe sepsis.
AB  - BACKGROUND: High levels of tumor necrosis factor (TNF) alpha messenger RNAs and
      interleukin (IL) 8 have been reported in leukocytes of patients with sepsis.
      HYPOTHESIS: Assessment of leukocyte intracytoplasmic levels of proinflammatory
      and anti-inflammatory cytokines might be clinically more relevant to determine
      prognosis in patients with severe sepsis. DESIGN: Cohort study. SETTING: Surgical
      intensive care units of a university hospital. PATIENTS AND INTERVENTIONS:
      Leukocyte suspensions obtained from 16 patients, 6 during early sepsis or septic
      shock and 10 during late sepsis or septic shock, were incubated with anti-CD14
      and anti-CD2 or anti-CD3 monoclonal antibodies and then with intracytoplasmic
      anticytokine antibodies staining for interferon-gamma, TNF-alpha, IL-2, IL-6, IL
      8, IL-10, and IL-12 and analyzed with a flow cytometer. MAIN OUTCOME MEASURES:
      Mann-Whitney test and Spearman correlation test were used in statistical
      evaluations according to the 28-day all-cause mortality rates and multiple organ
      dysfunction and sepsis-related organ failure assessment scores. RESULTS: Higher
      serum IL-6, IL-8, C-reactive protein, and procalcitonin levels were found in
      patients with high multiple organ dysfunction and sepsis-related organ failure
      assessment scores (greater than or equal to the median values [8 and 11,
      respectively]), in contrast to decreased T-lymphocyte-associated IL-6 and TNF
      alpha and monocyte-associated IL-10 and IL-12 proportions. Furthermore, in 28-day
      all-cause mortality analysis, there were higher levels of C-reactive protein and
      procalcitonin in nonsurvivors (n = 9) than in survivors (n = 7), while T
      lymphocyte-associated IL-2, IL-6, IL-10, and TNF-alpha and monocyte-associated IL
      10 and TNF-alpha proportions decreased in the nonsurvivors. CONCLUSION: These
      results suggest that diminished lymphocyte- and monocyte-associated
      proinflammatory and anti-inflammatory cytokine levels are associated with worse
      prognosis in patients with severe sepsis.

PMID- 12215157
TI  - Selection of pancreaticojejunostomy techniques according to pancreatic texture
      and duct size.
AB  - HYPOTHESIS: Selection of proper pancreaticojejunostomy techniques according to
      pancreatic texture and the main duct size reduces the pancreatic fistula rate.
      DESIGN AND PATIENTS: Data from 50 consecutive patients undergoing
      pancreatoduodenectomy with 3 different anastomotic techniques prospectively used
      according to pancreatic texture and the main duct size were analyzed. Duct
      invagination anastomosis was selected for pancreata with a small duct (n = 34 [29
      with a soft texture and 5 with a hard texture]). Stitches between the stump
      parenchyma and the jejunal seromuscular layer were added to this anastomosis
      procedure only for the hard pancreata. Pancreata with a large duct were
      reconstructed with a conventional duct-to-mucosa anastomosis (n = 16). SETTING: A
      university hospital department of digestive surgery. RESULTS: The morbidity was
      40% (20 of 50 patients) in this series. Four patients (8%) with a soft pancreas
      and a small duct developed a pancreatic stump leak after duct-invagination
      anastomosis, but all of them were removed without sequelae. No pancreatic
      anastomotic leak was seen in this series, which resulted in no mortality, no
      remnant pancreatectomy, and only 1 relaparotomy in the consecutive 50 patients.
      CONCLUSION: The proper selection of pancreatic reconstruction techniques
      according to our criteria may reduce the pancreatic fistula rate, eliminate risky
      pancreatic anastomotic leaks, and result in excellent outcomes for those
      undergoing pancreatoduodenectomy.

PMID- 12215159
TI  - Effects of delayed wound excision and grafting in severely burned children.
AB  - HYPOTHESIS: Advances in burn treatment including early excision of the wound have
      increased survival in patients treated at specialized burn centers. We
      hypothesized that the patients with delayed wound excision and grafting would
      experience deleterious outcomes. METHODS: From 1995 to 1999, 157 children with
      acute burns covering 40% or more of total body surface area and having more than
      10% of full-thickness burns were admitted to our institution within 2 weeks of
      injury. Among them, 86, 42, and 29 patients underwent first operation on days 0
      to 2, days 3 to 6, and days 7 to 14 after burn, respectively. Outcomes observed
      were mortality, number of operative procedures, length of hospitalization, blood
      transfused, incidence of wound bacterial and fungal contamination, invasive wound
      infection, and sepsis. RESULTS: Demographic data for the groups showed no
      differences in sex or total body surface area burned. Mortality and number of
      operative procedures and blood transfusions were not different between groups.
      Hospitalizations were longer in the delayed groups, which was associated with a
      higher incidence of significant wound contamination (P =.008). Invasive wound
      infection also increased significantly with delay of excision (P<.001). An
      increased incidence of sepsis was seen in patients with delayed wound excision
      and grafting (P =.04). CONCLUSIONS: Delays in excision were associated with
      longer hospitalization and delayed wound closure, as well as increased rates of
      invasive wound infection and sepsis. Our data indicate that early excision within
      48 hours is optimal for pediatric patients with massive burns.

PMID- 12215160
TI  - Worldwide trends in the surgical treatment of primary hyperparathyroidism in the
      era of minimally invasive parathyroidectomy.
AB  - HYPOTHESIS: Minimally invasive surgery for primary hyperparathyroidism has become
      an accepted part of endocrine surgical practice worldwide. DESIGN: Survey of
      members of the International Association of Endocrine Surgeons. SETTING: Clinical
      practice of endocrine surgeons worldwide. MAIN OUTCOME MEASURES: Numbers of
      parathyroid procedures performed, types of minimally invasive procedures
      undertaken, and techniques used to ensure completeness of removal of
      hyperfunctioning parathyroid tissue as reported by the survey respondents.
      RESULTS: Of 160 surveys completed, 95 (59%) indicate that the surgeons currently
      perform minimally invasive parathyroidectomy and use this technique on average
      for 44% of patients with primary hyperparathyroidism. The most common approach is
      the focused technique with a small incision, either central or lateral (92% [87
      respondents]), followed by a video-assisted technique (22% [21 respondents]), and
      a true endoscopic technique with gas insufflation (12% [11 respondents]).
      Techniques used to ensure completeness of resection include the quick
      intraoperative intact parathyroid hormone assay (68% [65 respondents]), a same
      day intact parathyroid hormone assay (17% [16 respondents]), and the nuclear
      probe (14% [13 respondents]). The number of parathyroidectomies performed
      worldwide increased from 1727 in 1980 to 6977 in 2000 with the average number per
      surgeon increasing from 23 in 1980 to 45 in 2000. Geographically, 20 (59%) of 34
      surveys from the Americas report the use of minimally invasive parathyroidectomy,
      23 (56%) of 41 from the Australasian region, and 34 (49%) of 69 from Europe or
      the Middle East. CONCLUSIONS: The number of parathyroidectomies performed for
      primary hyperparathyroidism has increased worldwide over the past 20 years. More
      than half of the surgeons responding to the survey perform minimally invasive
      parathyroidectomy, with the most using the focused small-incision technique.

PMID- 12215161
TI  - Infected pancreatic necrosis: translumbar approach and management with
      retroperitoneoscopy.
AB  - HYPOTHESIS: The extraperitoneal translumbar approach and retroperitoneoscopy are
      useful in the treatment and follow-up of patients with infected pancreatic
      necrosis. DESIGN: Descriptive study. SETTING: University hospital. PATIENTS:
      Fifteen consecutive patients with infected and drained pancreatic necrosis.
      INTERVENTIONS: Extraperitoneal translumbar approach to drain and
      retroperitoneoscopy as a method to propose evolutive control. MAIN OUTCOME
      MEASURES: Morbidity and mortality. RESULTS: Four (27%) of 15 patients died, and 3
      (20%) of 15 patients experienced complications during hospital admission.
      CONCLUSIONS: The retroperitoneal access to infected pancreatic necrosis has low
      rates of mortality and morbidity and a low percentage of repeated surgeries, and
      retroperitoneoscopy facilitates evolutive control of treated infected pancreatic
      necrosis.

PMID- 12215163
TI  - Compression stockings and venous function.
AB  - HYPOTHESIS: Surgical compression stockings measurably improve venous physiologic
      mechanisms, and stocking brands do not differ from one another. METHODS: Eleven
      patients, (8 men and 3 women [mean age, 53 years]), were included. Six patients
      had primary venous insufficiency and 5 patients had secondary venous
      insufficiency; 5 patients were in CEAP class 4 and 6 were in CEAP class 5.
      Patients were randomly assigned to a sequence of 4 brands of knee-high, open-toe,
      30- to 40-mm Hg stockings. Each patient wore a stocking for a 1-month
      equilibration period, then a different stocking monthly for 4 months in a row.
      Air plethysmography examinations were performed with and without stockings before
      and after each month of wear. Patients filled out a daily stocking record log and
      a monthly satisfaction survey. Stockings underwent compression testing after use.
      RESULTS: Stockings controlled reflux better than they improved calf muscle pump
      function. With stockings on, patients in CEAP 4 benefited more than those in CEAP
      5 in decreasing reflux, while patients in CEAP 5 benefited more than those in
      CEAP 4 in improving calf muscle pump function. Changes in residual volume
      fraction were improved in patients in CEAP 5 wearing stockings but not in
      patients in CEAP 4. Patients with primary disease had greater volumes of reflux
      and calf ejection than with secondary disease. There were no hemodynamic
      differences between stocking brands but there were differences in patient
      compliance and acceptance. CONCLUSIONS: Surgical support stockings seem to be
      more effective in controlling reflux than in improving calf muscle pump function.
      All stocking brands function equally as measured by air plethysmography.

PMID- 12215164
TI  - Prediction of distant metastasis by using reverse transcriptase-polymerase chain
      reaction for epithelial and variant CD44 mRNA in the peripheral blood of patients
      with colorectal cancer.
AB  - BACKGROUND: Reverse transcriptase-polymerase chain reaction (RT-PCR) has been
      used to identify small numbers of tumor cells. Molecular detection is thought to
      provide useful information for the clinical management of postoperative adjuvant
      therapy regimens. OBJECTIVE: To use RT-PCR to identify messenger RNA (mRNA)
      coding for carcinoembryonic antigen, epithelial and variant CD44, and matrix
      metalloproteinase 7 in the portal venous and peripheral blood of patients with
      colorectal carcinoma to predict live or distant metastasis. DESIGN: Prospective
      consecutive series. SETTING: University hospital. PATIENTS AND METHODS: Portal
      venous and peripheral blood samples were obtained from 22 patients with
      colorectal cancer during surgical manipulation. Using complementary DNA primers
      specific for carcinoembryonic antigen, CD44, and matrix metalloproteinase 7, RT
      PCR was performed to detect tumor cells. MAIN OUTCOME MEASURE: The clinical
      significance of RT-PCR for epithelial and variant CD44 mRNA in peripheral blood.
      RESULTS: During 3 years of follow-up, 2 patients whose peripheral blood had
      carcinoembryonic antigen and CD44 variant mRNA also had distant metastases (lung
      or spleen). Expression of epithelial and variant CD44 mRNA in peripheral blood
      was more highly correlated with the clinical cancer stage than with expression of
      carcinoembryonic antigen and matrix metalloproteinase 7. CONCLUSIONS: Molecular
      detection of epithelial and variant CD44 mRNA in the peripheral blood may help
      determine distant metastases in patients with colorectal carcinoma. Molecular
      detection in the peripheral blood at surgical treatment suggests that systemic
      hematogenic tumor cell dissemination is an early event of distant metastasis.

PMID- 12215165
TI  - Image of the month. Hepatic artery aneurysm.

PMID- 12215166
TI  - Temporary abdominal coverage in critically ill patients.

PMID- 12215167
TI  - Axillary lymphadenectomy and drains.

PMID- 12215168
TI  - The X generation.

PMID- 12215169
TI  - Moments in surgical history: Andrew Jackson Howe (1825-1892) and eclectic
      surgery.

PMID- 12215170
TI  - Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation
      at the beta-carbon of asparagine-803.
AB  - Asparagine-803 in the C-terminal transactivation domain of human hypoxia
      inducible factor (HIF)-1 alpha-subunit is hydroxylated by factor inhibiting HIF-1
      (FIH-1) under normoxic conditions causing abrogation of the HIF-1alpha/p300
      interaction. NMR and other analyses of a hydroxylated HIF fragment produced in
      vitro demonstrate that hydroxylation occurs at the beta-carbon of Asn-803 and
      imply production of the threo -isomer, in contrast with other known aspartic
      acid/asparagine hydroxylases that produce the erythro -isomer.

PMID- 12215171
TI  - Oxidative stress increases eukaryotic initiation factor 4E phosphorylation in
      vascular cells.
AB  - Dysregulated cell growth can be caused by increased activity of protein synthesis
      eukaryotic initiation factor (eIF) 4E. Dysregulated cell growth is also
      characteristic of atherosclerosis. It is postulated that exposure of vascular
      cells, such as endothelial cells, smooth muscle cells and monocytes/macrophages,
      to oxidants, such as oxidized low-density lipoprotein (oxLDL), leads to the
      elaboration of growth factors and cytokines, which in turn results in smooth
      muscle cell hyperproliferation. To investigate whether activation of eIF4E might
      play a role in this hyperproliferative response, vascular cells were treated with
      oxLDL, oxidized lipid components of oxLDL and several model oxidants, including
      H(2)O(2) and dimethyl naphthoquinone. Exposure to each of these compounds led to
      a dose- and time-dependent increase in eIF4E phosphorylation in all three types
      of vascular cells, correlated with a modest increase in overall translation rate.
      No changes in eIF4EBP, eIF2 or eIF4B modification state were observed. Increased
      eIF4E phosphorylation was paralleled by increased presence of eIF4E in high
      molecular-mass protein complexes characteristic of its most active form. Anti
      oxidants at concentrations typically employed to block oxidant-induced cell
      signalling likewise promoted eIF4E phosphorylation. The results of this study
      indicate that increased eIF4E activity may contribute to the pathophysiological
      events in early atherogenesis by increasing the expression of translationally
      inefficient mRNAs encoding growth-promoting proteins.

PMID- 12215172
TI  - Protein kinase C- and calcium-regulated pathways independently synergize with Gi
      pathways in agonist-induced fibrinogen receptor activation.
AB  - Platelet fibrinogen receptor activation is a critical step in platelet plug
      formation. The fibrinogen receptor (integrin alphaIIbbeta3) is activated by
      agonist-mediated G(q) stimulation and resultant phospholipase C activation. We
      investigated the role of downstream signalling events from phospholipase C,
      namely the activation of protein kinase C (PKC) and rise in intracellular
      calcium, in agonist-induced fibrinogen receptor activation using Ro 31-8220 (a
      PKC inhibitor) or dimethyl BAPTA [5,5'-dimethyl-bis-(o-aminophenoxy)ethane
      N,N,N', N'-tetra-acetic acid], a high-affinity calcium chelator. All the
      experiments were performed with human platelets treated with aspirin, to avoid
      positive feedback from thromboxane A2. In the presence of Ro 31-8220, platelet
      aggregation caused by U46619 was completely inhibited while no effect or partial
      inhibition was seen with ADP and the thrombin-receptor-activating peptide SFLLRN,
      respectively. In the presence of intracellular dimethyl BAPTA, ADP- and U46619
      induced aggregation and anti-alphaIIbbeta3 antibody PAC-1 binding were completely
      abolished. However, similar to the effects of Ro 31-8220, dimethyl BAPTA only
      partially inhibited SFLLRN-induced aggregation, and was accompanied by diminished
      dense-granule secretion. When either PKC activation or intracellular calcium
      release was abrogated, aggregation and fibrinogen receptor activation with U46619
      or SFLLRN was partially restored by additional selective activation of the G(i)
      signalling pathway. In contrast, when both PKC activity and intracellular calcium
      increase were simultaneously inhibited, the complete inhibition of aggregation
      that occurred in response to either U46619 or SFLLRN could not be restored with
      concomitant G(i) signalling. We conclude that, while the PKC- and calcium
      regulated signalling pathways are capable of inducing activating fibrinogen
      receptor independently and that each can synergize with G(i) signalling to cause
      irreversible fibrinogen receptor activation, both pathways act synergistically to
      effect irreversible fibrinogen receptor activation.

PMID- 12215175
TI  - Probiotics and health. Foreword.

PMID- 12215176
TI  - Probiotics and inflammatory bowel disease: from fads and fantasy to facts and
      future.
AB  - Probiotic therapy is attracting the renewed interest of clinicians and basic
      investigators from a variety of traditional research disciplines. While the
      theoretical rationale for modifying the commensal flora of the gastrointestinal
      tract in specific circumstances appears sound and requires scientific pursuit,
      the field of probiotics has been clouded by exaggerated claims from some
      quarters. In general, many of the claims for therapeutic efficacy have not been
      well substantiated, but the field is now poised for evaluation within the realm
      of evidence-based medicine. Alterations in commensal bacterial flora within the
      gastrointestinal tract are associated with susceptibility to pathogens such as
      Clostridium difficile and there is persuasive evidence that the normal flora may
      participate in the pathogenesis of inflammatory bowel disease and other chronic
      diseases in genetically susceptible individuals. This has prompted various
      strategies to fortify or otherwise modify the enteric flora by dietary
      supplements containing probiotic formulations. Detailed comparisons of probiotic
      performance amongst different bacterial strains have not been performed in vivo
      in man or under clinical trial conditions, and the level of scientific
      characterisation of individual organisms has been variable. In addition, it
      cannot be assumed that the same probiotic is equally suitable for all
      individuals. Moreover, the heterogeneity of clinical disorders such as Crohn's
      disease and ulcerative colitis implies that strain-specific properties may be
      required for subset-specific categories of patients. While cocktails of
      probiotics offer convenience, therapeutic progress may require clarification of
      the mechanism of probiotic action and may be delayed until individual bacterial
      components have been rigorously studied. More importantly, the full potential of
      therapeutic manipulation of the enteric flora with probiotics or other strategies
      may not be optimally realised until the composition and metabolic activities of
      the normal flora are better understood.

PMID- 12215173
TI  - Isolation and characterization of new Saccharomyces cerevisiae mutants perturbed
      in nuclear pore complex assembly.
AB  - BACKGROUND: Nuclear pore complexes (NPCs) are essential for facilitated,
      directional nuclear transport; however, the mechanism by which ~30 different
      nucleoporins (nups) are assembled into NPCs is unknown. We combined a genetic
      strategy in Saccharomyces cerevisiae with Green Fluorescence Protein (GFP)
      technology to identify mutants in NPC structure, assembly, and localization. To
      identify such mutants, a bank of temperature sensitive strains was generated and
      examined by fluorescence microscopy for mislocalization of GFP-tagged nups at the
      non-permissive temperature. RESULTS: A total of 121 mutant strains were isolated,
      with most showing GFP-Nic96 and Nup170-GFP mislocalized to discrete, cytoplasmic
      foci. By electron microscopy, several mutants also displayed an expansion of the
      endoplasmic reticulum (ER). Complementation analysis identified several mutant
      groups with defects in components required for ER/Golgi trafficking (sec13,
      sec23, sec27, and bet3). By directed testing, we found that mutant alleles of all
      COPII components resulted in altered GFP-Nup localization. Finally, at least nine
      unknown complementation groups were identified that lack secretion defects.
      CONCLUSION: The isolation of sec mutants in the screen could reflect a direct
      role for vesicle fusion or the COPII coat during NPC assembly; however, only
      those sec mutants that altered ER structure affected Nup localization. This
      suggests that the GFP-Nup mislocalization phenotypes observed in these mutants
      were the indirect result of overproliferation of the ER and connected outer
      nuclear envelope. The identification of potentially novel mutants with no
      secretory defects suggests the distinct GFP-Nup localization defects in other
      mutants in the collection will provide insights into NPC structure and assembly.

PMID- 12215177
TI  - Intestinal flora during the first months of life: new perspectives.
AB  - Increasing awareness that the human intestinal flora is a major factor in health
      and disease has led to different strategies to manipulate the flora to promote
      health. The complex microflora of the adult is difficult to change in the long
      term. There is greater impact of diet on the infant microflora. Manipulation of
      the flora particularly with probiotics has shown promising results in the
      prevention and treatment of diarrhoea and allergy. Before attempting to change
      the flora of the infant population in general, a greater understanding of the gut
      bacterial colonisation process is required. The critical stages of gut
      colonisation are after birth and during weaning. Lactic acid bacteria dominate
      the flora of the breast-fed infant. The formula-fed infant has a more diverse
      flora. The faeces of the breast-fed infant contain mainly acetic and lactic acid
      whereas the formula fed-infant has mainly acetic and propionic acid. Butyric acid
      is not a significant component in either group. The formula-fed infant also has
      higher faecal ammonia and other potentially harmful bacterial products. The
      composition of the microflora diversifies shortly before and particularly after
      weaning. The flora of the formula-fed infant develops more quickly than that of
      the breast-fed infant. Before embarking on any strategy to change the flora, the
      following questions should be considered: Should we retain a breast-fed style
      flora with limited ability to ferment complex carbohydrates? Can pro- and
      prebiotics achieve a flora with adult characteristics but with more lactic acid
      bacteria in weaned infants? Are there any health risks associated with such
      manipulations of the flora?

PMID- 12215178
TI  - Probiotics: on-going research on atopic individuals.
AB  - The challenge for the modern health care system is to fight against the
      increasing prevalence of atopic disease. The introduction of scientifically
      composed probiotic functional foods for prophylactic or therapeutic purposes
      could be one solution. Probiotics are live microbial food supplements or
      components of bacteria which have beneficial effects on human health. Specific
      strains have been demonstrated to exert powerful anti-pathogenic, anti
      inflammatory and anti-allergic effects. The hygiene hypothesis suggests that
      atopic disease may arise from a lack of counterbalancing microbial exposure at an
      early age. The initial compositional development of the gut microflora is
      considered a key determinant of the development of both the immune responder
      phenotype and normal gut barrier functions. The regulatory role of probiotics in
      human allergic disease was first emphasised in the demonstration of a suppressive
      effect on lymphocyte proliferation and interleukin-4 generation in vitro.
      Subsequently, a significant improvement in the clinical course of atopic eczema
      was reported in infants given a probiotic-supplemented diet. The potential of
      probiotics to reduce the risk of atopic disease has recently been demonstrated in
      a double-blind, placebo-controlled study: probiotics administered pre- and
      postnatally for 6 months to at-risk subjects reduced the prevalence of atopic
      eczema to half of that observed in infants receiving placebo. Ongoing research is
      directed towards the development of novel techniques to characterise the gut
      microflora. Future research will clarify the mechanisms to control specific
      physiological processes in the evolution of atopic disease in at-risk populations
      or in the management of allergic diseases.

PMID- 12215179
TI  - Application of molecular biological methods for studying probiotics and the gut
      flora.
AB  - Increasingly, the microbiological scientific community is relying on molecular
      biology to define the complexity of the gut flora and to distinguish one organism
      from the next. This is particularly pertinent in the field of probiotics, and
      probiotic therapy, where identifying probiotics from the commensal flora is often
      warranted. Current techniques, including genetic fingerprinting, gene sequencing,
      oligonucleotide probes and specific primer selection, discriminate closely
      related bacteria with varying degrees of success. Additional molecular methods
      being employed to determine the constituents of complex microbiota in this area
      of research are community analysis, denaturing gradient gel electrophoresis
      (DGGE)/temperature gradient gel electrophoresis (TGGE), fluorescent in situ
      hybridisation (FISH) and probe grids. Certain approaches enable specific
      aetiological agents to be monitored, whereas others allow the effects of dietary
      intervention on bacterial populations to be studied. Other approaches demonstrate
      diversity, but may not always enable quantification of the population. At the
      heart of current molecular methods is sequence information gathered from
      culturable organisms. However, the diversity and novelty identified when applying
      these methods to the gut microflora demonstrates how little is known about this
      ecosystem. Of greater concern is the inherent bias associated with some molecular
      methods. As we understand more of the complexity and dynamics of this diverse
      microbiota we will be in a position to develop more robust molecular-based
      technologies to examine it. In addition to identification of the microbiota and
      discrimination of probiotic strains from commensal organisms, the future of
      molecular biology in the field of probiotics and the gut flora will, no doubt,
      stretch to investigations of functionality and activity of the microflora, and/or
      specific fractions. The quest will be to demonstrate the roles of probiotic
      strains in vivo and not simply their presence or absence.

PMID- 12215180
TI  - Probiotics as modulators of the gut flora.
AB  - Probiotic ingestion can be recommended as a preventative approach to maintaining
      the balance of the intestinal microflora and thereby enhance 'well-being'.
      Research into the use of probiotic intervention in specific illnesses and
      disorders has identified certain patient populations that may benefit from the
      approach. Undoubtedly, probiotics will vary in their efficacy and it may not be
      the case that the same results occur with all species. Those that prove most
      efficient will likely be strains that are robust enough to survive the harsh
      physico-chemical conditions present in the gastrointestinal tract. This includes
      gastric acid, bile secretions and competition with the resident microflora. A
      survey of the literature indicates positive results in over fifty human trials,
      with prevention/treatment of infections the most frequently reported output. In
      theory, increased levels of probiotics may induce a 'barrier' influence against
      common pathogens. Mechanisms of effect are likely to include the excretion of
      acids (lactate, acetate), competition for nutrients and gut receptor sites,
      immunomodulation and the formation of specific antimicrobial agents. As such,
      persons susceptible to diarrhoeal infections may benefit greatly from probiotic
      intake. On a more chronic basis, it has been suggested that some probiotics can
      help maintain remission in the inflammatory conditions, ulcerative colitis and
      pouchitis. They have also been suggested to repress enzymes responsible for
      genotoxin formation. Moreover, studies have suggested that probiotics are as
      effective as anti-spasmodic drugs in the alleviation of irritable bowel syndrome.
      The approach of modulating the gut flora for improved health has much relevance
      for the management of those with acute and chronic gut disorders. Other target
      groups could include those susceptible to nosocomial infections, as well as the
      elderly, who have an altered microflora, with a decreased number of beneficial
      microbial species. For the future, it is imperative that mechanistic interactions
      involved in probiotic supplementation be identified. Moreover, the survival
      issues associated with their establishment in the competitive gut ecosystem
      should be addressed. Here, the use of prebiotics in association with useful
      probiotics may be a worthwhile approach. A prebiotic is a dietary carbohydrate
      selectively metabolised by probiotics. Combinations of probiotics and prebiotics
      are known as synbiotics.

PMID- 12215181
TI  - Probiotics and non-intestinal infectious conditions.
AB  - Orally ingested probiotic micro-organisms do not exert health effects exclusively
      in the intestine. Some strains can alleviate or prevent bacterial, fungal or
      viral infections in other organs by stimulation of the immune system. By
      preservation or improvement of the barrier function of the intestinal mucosa,
      they may inhibit translocation of potential pathogens and thus prevent infections
      of the blood stream and other tissues and organs. Modulation of the intestinal
      microflora can affect the local microflora of the urogenital tract and possibly
      of the oral cavity. Finally, some strains of orally ingested bacteria reach
      target organs like the urogenital tract in a viable state; alternatively they can
      be applied locally. Despite the infection-preventing properties of probiotic
      bacteria, lactic acid bacteria have rarely been identified in infections of the
      blood stream, heart valves and other organs, usually only in patients with severe
      disease. It is the general opinion that in most cases the source of infection was
      the commensal microflora of the intestine or the oral cavity. Until now only one
      case of infection associated with administration of a probiotic strain has been
      published. The most promising health-promoting effects have been seen in
      vaginosis, urinary tract infections, Helicobacter pylori gastritis and infections
      of the respiratory tract in children. More controlled clinical trials with
      sufficient numbers of participants are needed to determine the scientific basis
      for the use of probiotic bacteria in infections in locations of the body other
      than the intestine.

PMID- 12215182
TI  - A review of the role of the gut microflora in irritable bowel syndrome and the
      effects of probiotics.
AB  - Irritable bowel syndrome (IBS) is a multi-factorial gastrointestinal condition
      affecting 8-22 % of the population with a higher prevalence in women and
      accounting for 20-50 % of referrals to gastroenterology clinics. It is
      characterised by abdominal pain, excessive flatus, variable bowel habit and
      abdominal bloating for which there is no evidence of detectable organic disease.
      Suggested aetiologies include gut motility and psychological disorders,
      psychophysiological phenomena and colonic malfermentation. The faecal microflora
      in IBS has been shown to be abnormal with higher numbers of facultative organisms
      and low numbers of lactobacilli and bifidobacteria. Although there is no evidence
      of food allergy in IBS, food intolerance has been identified and exclusion diets
      are beneficial to many IBS patients. Food intolerance may be due to abnormal
      fermentation of food residues in the colon, as a result of disruption of the
      normal flora. The role of probiotics in IBS has not been clearly defined. Some
      studies have shown improvements in pain and flatulence in response to probiotic
      administration, whilst others have shown no symptomatic improvement. It is
      possible that the future role of probiotics in IBS will lie in prevention, rather
      than cure.

PMID- 12215183
TI  - Lactic acid bacteria and cancer: mechanistic perspective.
AB  - Colorectal cancer is one of the most important causes of cancer morbidity and
      mortality in Western countries. While a myriad of healthful effects have been
      attributed to the probiotic lactic acid bacteria (LAB), perhaps the most
      controversial remains that of anticancer activity. It should be pointed out that
      there is no direct experimental evidence for cancer suppression in man as a
      result of consumption of lactic cultures in fermented or unfermented dairy
      products. However, there is a wealth of indirect evidence, based largely on
      laboratory studies, in the literature. The precise mechanisms by which LAB may
      inhibit colon cancer are presently unknown. However, such mechanisms might
      include: alteration of the metabolic activities of intestinal microflora;
      alteration of physico-chemical conditions in the colon; binding and degrading
      potential carcinogens; quantitative and/or qualitative alterations in the
      intestinal microflora incriminated in producing putative carcinogen(s) and
      promoters (e.g. bile acid-metabolising bacteria); production of antitumourigenic
      or antimutagenic compounds; enhancing the host's immune response; and effects on
      physiology of the host. These potential mechanisms are addressed in the present
      paper.

PMID- 12215184
TI  - Competition for adhesion between probiotics and human gastrointestinal pathogens
      in the presence of carbohydrate.
AB  - The adhesion of Lactobacillus rhamnosus GG to human enterocyte-like Caco-2 cells
      was not inhibited by eight carbohydrates tested, namely N-acetyl-glucosamine,
      galactose, glucose, fructose, fucose, mannose, methyl-alpha-D-mannopyranoside and
      sucrose. The degree of hydrophobicity predicted the adhesion of L. rhamnosus GG
      to Caco-2 cells. L. rhamnosus GG, however, was able to compete with Escherichia
      coli and Salmonella spp. of low hydrophobicity and high adhesin-receptor
      interaction for adhesion to Caco-2 cells. The interference of adhesion of these
      gastrointestinal (GI) bacteria by L. rhamnosus GG was probably through steric
      hindrance, and the degree of inhibition was related to the distribution of the
      adhesin receptors and hydrophobins on the Caco-2 surface. A Carbohydrate Index
      for Adhesion (CIA) was used to depict the binding property of adhesins on
      bacteria surfaces. CIA was defined as the sum of the fraction of adhesion in the
      presence of carbohydrates, with reference to the adhesion measured in the absence
      of any carbohydrate. The degree of competition for receptor sites between
      Lactobacillus casei Shirota and GI bacteria is a function of their CIA distance.
      There were at least two types of adhesins on the surface of L. casei Shirota. The
      study provides a scientific basis for the screening and selection of probiotics
      that compete with selective groups of pathogens for adhesion to intestinal
      surfaces. It also provides a model for the characterisation of adhesins and
      adhesin-receptor interactions.

PMID- 12215186
TI  - Diet and cancer: assessing the risk.
AB  - Globally, colorectal cancer (CRC) is a leading cause of mortality from malignant
      disease. Case-control and cohort studies provide strong support for a role of
      diet in the aetiology of CRC. However to establish causal relationships and to
      identify more precisely the dietary components involved, intervention studies in
      human subjects are required. Cancer is an impractical endpoint in terms of
      numbers, cost, study duration and ethical considerations. Consequently,
      intermediate biomarkers of the disease are required. This review aims to provide
      an overview of the intermediate endpoints available for the study of CRC,
      particularly non-invasive faecal biomarkers. Examples of their use in dietary
      intervention studies are given.

PMID- 12215185
TI  - Probiotics and intestinal health effects: a clinical perspective.
AB  - Probiotics are viable non-pathogenic micro-organisms which, when ingested, exert
      a positive influence on host health or physiology. We have critically analysed
      the evidence for the efficacy of specific probiotic strains in human
      gastrointestinal diseases. The best evidence can be obtained with randomised
      controlled trials which avoid bias. Good evidence has been obtained with several
      strains in the prevention or treatment of antibiotic-associated disorders, in the
      treatment (and to a lesser extent prevention) of gastroenteritis and acute
      diarrhoea and in the alleviation of lactose intolerance. We also analysed the
      recent randomised controlled trials performed in patients with Clostridium
      difficile or Helicobacter pylori, inflammatory bowel disease, irritable bowel
      syndrome, non-ulcer dyspepsia and colon cancer.

PMID- 12215187
TI  - Improvement of the probiotic effect of micro-organisms by their combination with
      maltodextrins, fructo-oligosaccharides and polyunsaturated fatty acids.
AB  - Probiotics could represent an effective alternative to the use of synthetic
      substances in nutrition and medicine. The data concerning the efficacy of
      probiotics are often contradictory. This paper focuses on the enhancement of the
      efficacy of probiotics by their combination with synergistically acting
      components of natural origin. Maltodextrins can be obtained by enzymatic
      hydrolysis of starch and are suitable for consumption. Administration of
      Lactobacillus paracasei together with maltodextrin decreased the number of
      Escherichia coli colonising the jejunal mucosa of gnotobiotic piglets by 1
      logarithm compared to the control group. Fructo-oligosaccharides (FOS) are
      naturally occurring oligosaccharides, mainly of plant origin. L. paracasei
      administered in combination with FOS significantly increased counts of
      Lactobacillus spp., Bifidobacterium spp., total anaerobes and total aerobes
      compared to the control group as well as the L. paracasei group. It also
      significantly decreased Clostridium and Enterobacterium counts in the faeces of
      the weanling piglets compared with the control group. Dietary lipids influence
      the gastrointestinal microbiota and specifically the population of lactic acid
      bacteria. In gnotobiotic piglets the oral administration of an oil containing
      polyunsaturated fatty acids (PUFA) significantly increased the number of L.
      paracasei adhering to jejunal mucosa compared to the control group. Our results
      showed that maltodextrin KMS X-70 and PUFA can be used to enhance the effect of
      probiotic micro-organisms in the small intestine, and similarly FOS enhance the
      effect of probiotic micro-organisms in the large intestine.

PMID- 12215188
TI  - Two hearts are better than one?

PMID- 12215189
TI  - The ten most commonly asked questions about aortic stenosis.

PMID- 12215190
TI  - Primary pulmonary hypertension and cor pulmonale.
AB  - Primary pulmonary hypertension and cor pulmonale represent forms of precapillary
      pulmonary hypertension due to intrinsic lung disease. In the case of primary
      pulmonary hypertension, this is due to disease of the pulmonary vasculature while
      cor pulmonale is related to diseases of the pulmonary vasculature, airways, or
      interstitium. Patients present with signs and symptoms of right ventricular
      dysfunction and low cardiac output including dyspnea, chest pain and peripheral
      edema. Therapy is directed at the underlying disease and may include supplemental
      oxygen for diseases causing chronic hypoxemia and anticoagulation for thrombotic
      disease. Vasodilator therapy has variable efficacy for pulmonary vascular
      disorders. Postacyclin by continuous infusion has been a major advance in the
      therapy of primary pulmonary hypertension and has prolonged survival and delayed
      the need for lung transplantation. Bosentan, an endothelin receptor blocking
      agent is the first oral medication approved for the therapy of pulmonary
      hypertension.

PMID- 12215191
TI  - Spontaneous coronary artery dissection: report of two cases and a 50-year review
      of the literature.
AB  - Spontaneous coronary artery dissection (SCAD) is a rare condition that can cause
      acute myocardial infarction and sudden death. This entity occurs predominantly in
      women. Although several mechanisms have been postulated, no single etiology
      completely explains the pathogenesis of SCAD. Patients who survive SCAD have been
      treated with various modalities. Prompt diagnosis and early institution of
      appropriate treatment are usually associated with successful outcome. We report
      two cases of SCAD successfully identified and treated with coronary stenting as
      well as a comprehensive review of cases of SCAD published since 1952.

PMID- 12215192
TI  - Adverse dermatologic effects of cardiovascular drug therapy: part II.
AB  - Cardiovascular disease is common, affecting an increasing number of persons as
      the population ages. To combat this growing health problem, physicians use a
      multitude of medications in the treatment of their patients. Although
      pharmacologic therapy greatly enhances quality of life for a majority of
      patients, there is always the potential for an unfavorable reaction. For example,
      cardiovascular drugs can induce a vast array of adverse dermatologic responses.
      This article reviews the various cutaneous reaction patterns that can occur as a
      result of treatment with class III, IV, and other antiarrhythmic agents, ACE
      inhibitors, Angiotensin II receptor blockers, and diuretics.

PMID- 12215193
TI  - Effect of early statin therapy after acute coronary syndromes: a concise review
      of the recent data.
AB  - HMG Co-A reductase inhibitors(statins) have been shown, in three large randomized
      trials, to decrease adverse cardiac events in patients with clinically evident
      coronary artery disease. All of these trials have excluded patients with an acute
      coronary syndrome within the three months prior to enrollment. Statin therapy is
      thought to stabilize coronary plaque and decrease the risk of plaque rupture.
      Statins have been shown to quickly reduce levels of LDL-C in addition to altering
      systemic inflammatory responses, improving endothelial function, and reducing
      platelet aggregation and activation. These mechanisms are potentially beneficial
      in the setting of acute coronary syndromes, a time of profound plaque
      instability. There is a growing body of evidence supporting the early initiation
      of statin therapy in the setting of acute coronary syndromes. This paper reviews
      the available data from randomized-controlled trials and observational studies
      evaluating the effect of early statin initiation during, or soon following, an
      acute coronary syndrome.

PMID- 12215194
TI  - Diagnosis of myocardial injury by biochemical markers: problems and promises.
AB  - The role of biochemical markers in the diagnosis of acute coronary syndromes has
      increased considerably in the past decade. The World Health Organization
      previously defined acute myocardial infarction as a combination of at least 2 of
      3 components: symptoms consistent with acute myocardial infarction,
      electrocardiogram changes diagnostic of acute myocardial infarction, and an
      enzyme pattern with classic rise and fall. Measurement of creatine kinase and its
      MB fraction by various assays was the gold standard for the diagnosis. Troponins
      are more specific and sensitive markers for myocardial injury, and their
      increasing utilization has resulted in a broadening of the definition of acute
      myocardial infarction to incorporate high-risk acute coronary syndromes.
      Previously, traditional enzyme evaluation left patients with small amounts of
      cellular death undiagnosed; these patients were categorized as having unstable
      angina or, worse, noncardiac chest pain. Newer markers now identify these
      patients as a subgroup at high risk for cardiac death or cardiac events. Newer
      therapeutic interventions and a more invasive strategy have been shown to improve
      outcomes in this high-risk subgroup. Increased specificity has also reduced the
      number of patients who undergo extensive, expensive, and invasive evaluations for
      noncardiac syndromes due to false elevations of traditional markers. This article
      comprehensively reviews the evolution of biochemical markers for the diagnosis of
      acute myocardial infarction, addressing their promise for improving delivery of
      care and outcomes and their technical and diagnostic pitfalls.

PMID- 12215196
TI  - Death and method: the rhetorical space of seventeenth century vital measurement.

PMID- 12215197
TI  - 'The merchant's logick': numerical debates over smallpox inoculation in
      eighteenth-century England.

PMID- 12215198
TI  - The Annual report of the registrar general, 1839-1920: a textual history.

PMID- 12215199
TI  - Metrological awakenings: rationalising the body electric in nineteenth century
      medicine.

PMID- 12215200
TI  - The introduction of mathematical statistics into medical research: the roles of
      Karl Pearson, Major Greenwood and Austin Bradford Hill.

PMID- 12215201
TI  - Almroth Wright, vaccine therapy, and British biometrics: disciplinary expertise
      versus statistical objectivity.

PMID- 12215203
TI  - Redox control of T-cell death.

PMID- 12215204
TI  - Differential regulation of hydrogen peroxide and Fas-dependent apoptosis pathways
      by dehydroascorbate, the oxidized form of vitamin C.
AB  - Dehydroascorbate (DHA), the oxidized form of vitamin C (ascorbate), enhanced
      antioxidant defenses of human T cells preferentially importing DHA over
      ascorbate. In itself, DHA did not affect cytosolic or mitochondrial reactive
      oxygen intermediate levels as monitored by flow cytometry using oxidation
      sensitive fluorescent probes. DHA at 200-1,000 microM stimulated activity of
      pentose phosphate pathway enzymes glucose 6-phosphate dehydrogenase, 6
      phosphogluconate dehydrogenase, and transaldolase, elevated intracellular
      glutathione levels, and inhibited H(2)O(2)-induced changes in mitochondrial
      transmembrane potential and cell death. With respect to the CD4 antigen, DHA
      selectively enhanced cell-surface expression of the Fas receptor and increased
      susceptibility of Jurkat and H9 human T cells to Fas-mediated cell death. The
      data identify DHA as a selective regulator of H(2)O(2)- and Fas-dependent
      apoptosis pathways.

PMID- 12215205
TI  - Menadione biphasically controls JNK-linked cell death in leukemia Jurkat T cells.
AB  - Signals for cell-death induction by menadione were studied in Jurkat T cells. Low
      concentrations of menadione (10-20 microM) and H(2)O(2) (10-50 microM) induced
      cell death accompanying low (menadione: <5%) or moderate (H(2)O(2): 10-15%)
      levels of DNA fragmentation in Jurkat cells. These concentrations of menadione
      (10 microM) and H(2)O(2) also caused membrane (necrotic) cell death at
      unproportionally high (80%) and proportional (10-30%) levels, respectively.
      Higher concentrations (100-5,000 microM) of H(2)O(2) exclusively induced membrane
      cell death. Unexpectedly, 30-300 microM menadione induced ever-decreasing levels
      of necrotic cell death in a concentration-dependent manner. An in vitro kinase
      assay showed that 20-50 microM, but not >100 microM, menadione induced activation
      of c-Jun NH(2)-terminal kinase (JNK), whereas a striking activation of JNK was
      induced by 500-5,000 microM H(2)O(2). Induction of cell death by a low
      concentration of menadione was partially inhibited in dominant negative JNK gene
      transfected Jurkat/VPF cells. A high concentration (300 microM) of menadione was
      found to inhibit cell-death induction by high concentrations (200-5,000 microM)
      of H(2)O(2). The JNK inhibitory activity of menadione was also demonstrated in a
      cell-free system. However, menadione did not activate JNK in vitro. These results
      suggest that JNK is required for induction of not only apoptotic cell death, but
      also necrotic cell death in Jurkat T cells and that menadione biphasically
      controls this JNK-linked signal for inducing cell death.

PMID- 12215206
TI  - Mercury-induced apoptosis in human lymphocytes: caspase activation is linked to
      redox status.
AB  - There is growing evidence that heavy metals, in general, and mercurial compounds,
      in particular, are toxic to the human immune system. We have previously shown
      that methyl mercuric chloride (MeHgCl) is a potent human T-cell apoptogen;
      moreover, mitochondria appear to be a target organelle for the induction of cell
      death. The objective of this study was to determine the impact of MeHgCl on
      mitochondrial function in lymphocytes in terms of modulating reactive oxygen
      species (ROS) generation, thiol status, and caspase activation. Using the
      fluorescent probe, 3,3'-dihexyloxacarbocyanine, we demonstrated that exposure to
      MeHgCl for 1 h resulted in a profound decrease in the mitochondrial transmembrane
      potential. We next observed the release of cytochrome c from mitochondria into
      the cytosol; significant translocation was noted between 4 and 8 h following
      treatment with mercury. ROS generation was monitored by following the conversion
      of dihydroethidium to the fluorescent product, ethidium. Kinetic analysis
      indicated that ROS generation was maximal after 16 h of exposure to MeHgCl. The
      toxicant also depleted the thiol reserves of the cell; glutathione levels were
      depleted in a dose-dependent fashion reaching minimal levels at 16 h. Real-time
      RT-PCR analysis demonstrated a significant reduction in both glutathione S
      transferase and glutathione peroxidase gene expression in mercury-treated cells.
      Finally, after 16 h of treatment with MeHgCl, we observed activation of caspase
      8, -9, and -3 along with increased expression of caspase-8 and -9. We propose
      that the target organelle for MeHgCl is the mitochondrion and that induction of
      oxidative stress is critical to activation of death-signaling pathways.
      Additonally, mercury acts as a genotoxin significantly altering the expression of
      genes that affect cell survival and apoptosis.

PMID- 12215207
TI  - L-carnitine reduces lymphocyte apoptosis and oxidant stress in HIV-1-infected
      subjects treated with zidovudine and didanosine.
AB  - Apoptosis is critical to the progression of human immunodeficiency virus-1 (HIV
      1) infection. It appears reasonable that antiretroviral therapies may not achieve
      a full control of the infection in the absence of an impact on apoptosis. We
      assigned 20 asymptomatic HIV-infected subjects with advanced immunodeficiency to
      receive either zidovudine (AZT), and didanosine (DDI) or the same regimen plus L
      carnitine, a known antiapoptotic drug, for 7 months. Immunologic and virologic
      parameters were measured at baseline and after 15, 60, 120, and 210 days of
      treatment. We assessed on each time point the following: (a) the frequency of
      peripheral blood apoptotic CD4 and CD8 lymphocytes, CD4 and CD8 cells with
      disrupted mitochondrial membrane potential, and CD4 and CD8 cells undergoing
      oxidant stress; (b) the expression of the molecular markers of apoptosis Fas and
      caspase-1; and (c) the expression of p35/cdk-5 regulatory subunit that is
      involved in regulating cell survival and apoptosis. Absolute CD4 and CD8 counts
      and plasma viremia were also measured. Apoptotic CD4 and CD8 cells, lymphocytes
      with disrupted mitochondrial membrane potential, and lymphocytes undergoing
      oxidant stress were greatly reduced in subjects treated with AZT and DDI plus L
      carnitine compared with those who did not receive L-carnitine. Fas and caspase-1
      were down-expressed and p35 over-expressed in lymphocytes from patients of the L
      carnitine group. No difference was found in CD4 and CD8 counts and viremia
      between the groups. No toxicity of L-carnitine was recognized. The addition of L
      carnitine is safe and allows apoptosis and oxidant stress to be greatly reduced
      in lymphocytes from subjects treated with AZT and DDI.

PMID- 12215208
TI  - Redox control of cell death.
AB  - Cellular redox is controlled by the thioredoxin (Trx) and glutathione (GSH)
      systems that scavenge harmful intracellular reactive oxygen species (ROS).
      Oxidative stress also evokes many intracellular events including apoptosis. There
      are two major pathways through which apoptosis is induced; one involves death
      receptors and is exemplified by Fas-mediated caspase-8 activation, and another is
      the stress- or mitochondria-mediated caspase-9 activation pathway. Both pathways
      converge on caspase-3 activation, resulting in nuclear degradation and cellular
      morphological change. Oxidative stress induces cytochrome c release from
      mitochondria and activation of caspases, p53, and kinases, including apoptosis
      signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase, and p38 mitogen
      activated protein kinase. Trx inhibits apoptosis signaling not only by scavenging
      intracellular ROS in cooperation with the GSH system, but also by inhibiting the
      activity of ASK1 and p38. Mitochondria-specific thioredoxin (Trx-2) and Trx
      peroxidases (peroxiredoxins) are suggested to regulate cytochrome c release from
      mitochondria, which is a critical early step in the apoptotis-signaling pathway.
      dATP/ATP and reducing factors including Trx determine the manifestation of cell
      death, apoptosis or necrosis, by regulating the activation process and the
      activity of redox-sensitive caspases. As mitochondria are the most redox-active
      organelle and indispensable for cells to initiate or inhibit the apoptosis
      process, the regulation of mitochondrial function is the central focus in the
      research field of apoptosis and redox.

PMID- 12215209
TI  - Physiological roles of ASK1-mediated signal transduction in oxidative stress- and
      endoplasmic reticulum stress-induced apoptosis: advanced findings from ASK1
      knockout mice.
AB  - Apoptosis, a molecularly regulated form of cell death, is essential for the
      normal functioning and homeostasis of most multicellular organisms, and can be
      induced by a range of environmental, physical, and chemical stresses. As the
      cellular decision to live or to die is made by the coordinated action and
      balancing of many different pro- and antiapoptotic factors, defects in control of
      this coordination and balance may contribute to a variety of human diseases,
      including cancer and autoimmune and neurodegenerative conditions. In recent
      years, multiple factors associated with the execution of apoptosis, such as
      caspases and Bcl-2 family members, have been discovered and their complicated
      signaling and molecular interactions have been demonstrated; however, the precise
      mechanistic basis for intracellular and/or extracellular stress-induced apoptosis
      remains to be fully characterized. Protein kinases contribute to regulation of
      life and death decisions made in response to various stress signals, and the
      actions of pro- and antiapoptotic factors are often affected by modulation of the
      phosphorylation status of key elements in the execution of apoptosis. Apoptosis
      signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein
      (MAP) kinase kinase kinase family, which activates both the MKK4/MKK7-JNK and
      MKK3/MKK6-p38 MAP kinase pathways and constitutes a pivotal signaling pathway in
      various types of stress-induced apoptosis. We have recently shown through ASK1
      gene ablation in mice that ASK1 plays essential roles in oxidative stress- and
      endoplasmic reticulum (ER) stress-induced apoptosis. These stresses are closely
      linked to physiological phenomena in the control of cell fate, and the resultant
      apoptosis is implicated in the pathophysiology of a broad range of human
      diseases. This article reviews our new findings on the physiological roles of
      ASK1-mediated signal transduction in stress responses and the molecular
      mechanisms by which ASK1 determines cell fate such as survival, differentiation,
      or apoptosis, with special focus on the regulatory mechanisms of ASK1-mediated
      apoptosis induced by oxidative stress and ER stress.

PMID- 12215211
TI  - Redox-linked cell surface-oriented signaling for T-cell death.
AB  - T-cell death, which occurs either for ontogenic T-cell selection or for activated
      T-cell elimination, is normally induced through binding of a specific ligand to
      cell-surface T-cell receptor for crosslinkage. Heavy metals and carbonyl
      compounds that bind to protein-reactive groups such as cysteine sulfhydryl groups
      and lysine epsilon-amino groups may also induce crosslinkage of cell-surface
      proteins, in part replacing or modifying the ligand-mediated action. This
      chemical event has been found to accompany clustering of membrane rafts, to which
      signal-transducing elements such as glycosylphosphatidylinositol-anchored
      proteins and Src family protein tyrosine kinases (PTKs) are attached, and to
      trigger the signal transduction for apoptotic T-cell death, inducing
      mitochondrial membrane potential reduction, caspase activation and DNA
      fragmentation. As signals potentially upstream of this signaling, activations of
      PTKs and mitogen-activated protein (MAP) family kinases and production of
      reactive oxygen species (ROS) were induced following the cell-surface event, and
      crucial roles of activation of c-Jun amino-terminal kinase and apoptosis signal
      regulating kinase 1 by a redox-linked mechanism in the cell-death signaling were
      demonstrated. Intriguingly, ROS production as well as PTK/MAP family kinase
      activation occurred in a membrane raft integrity-dependent manner. The redox
      linked and cell surface-oriented signal delivery pathway demonstrated here may
      play an important role in induction of immune disorders by protein reactive group
      binding chemicals.

PMID- 12215210
TI  - Metabolic switches of T-cell activation and apoptosis.
AB  - The signaling networks that mediate activation, proliferation, or programmed cell
      death of T lymphocytes are dependent on complex redox and metabolic pathways. T
      lymphocytes are primarily activated through the T-cell receptor and co
      stimulatory molecules. Although activation results in lymphokine production,
      proliferation, and clonal expansion, it also increases susceptibility to
      apoptosis upon crosslinking of cell-surface death receptors or exposure to toxic
      metabolites. Activation signals are transmitted by receptor-associated protein
      tyrosine kinases and phosphatases through calcium mobilization to a secondary
      cascade of kinases, which in turn activate transcription factors initiating cell
      proliferation and cytokine production. Initiation and activity of cell death
      mediating proteases are redox-sensitive and dependent on energy provided by ATP.
      Mitochondria play crucial roles in providing ATP for T-cell activation through
      the electron transport chain and oxidative phosphorylation. The mitochondrial
      transmembrane potential (DeltaPsi(m)) plays a decisive role not only by driving
      ATP synthesis, but also by controlling reactive oxygen species production and
      release of cell death-inducing factors. DeltaPsi(m) and reactive oxygen species
      levels are regulated by the supply of reducing equivalents, glutathione and
      thioredoxin, as well as NADPH generated in the pentose phosphate pathway. This
      article identifies redox and metabolic checkpoints controlling activation and
      survival of T lymphocytes.

PMID- 12215212
TI  - Redox imbalance and its control in HIV infection.
AB  - Human immunodeficiency virus (HIV)-infected individuals are suffering from
      systemic oxidative stress. Reactive oxygen species act as second messengers for
      the activation of nuclear factor-kappaB (NF-kappaB), which augments the
      replication of HIV. Intracellular levels of glutathione (GSH), a major cytosolic
      antioxidant, in T cells decrease during the disease progression. Another redox
      regulating molecule, thioredoxin (TRX), is also transiently down-regulated in the
      cells by acute HIV infection. In contrast, plasma levels of TRX are elevated in
      the late stage of HIV infection. Intracellular GSH and plasma TRX can be
      biomarkers to predict the prognosis of the disease. N-Acetylcysteine (NAC), a
      prodrug of cysteine that is necessary for GSH synthesis, has been used for HIV
      infection to prevent the activation of NF-kappaB and the replication of HIV. NAC
      shows some beneficial effects for HIV-infected individuals, although the
      intracellular GSH levels in lymphocytes are not significantly restored. The
      control of imbalanced redox status by antioxidants may be beneficial for the
      quality of life in HIV infection even in the era after the effective therapy with
      protease inhibitors has been applied. Redox control will be an important
      therapeutic strategy for oxidative stress-associated disorders including HIV
      infection.

PMID- 12215213
TI  - Elevated oxidative stress in patients with ataxia telangiectasia.
AB  - Ataxia telangiectasia (AT) is a pleiotropic genetic disorder characterized by
      progressive neurodegeneration, especially of cerebellar Purkinje cells,
      immunodeficiency, increased incidence of cancer, and premature aging. The disease
      is caused by functional inactivation of the ATM (AT-mutated) gene product, which
      is thought to act as a sensor of reactive oxygen species and oxidative damage of
      cellular macromolecules and DNA. The compound phenotype of AT might thus be
      linked to a continuous state of oxidative stress leading to an increase of
      programmed cell death (apoptosis). To assess this hypothesis, we analyzed lipid
      peroxidation products and the oxidative stress associated DNA base damage 8
      hydroxy-2-deoxyguanosine in patients with AT. Oxidative damage to lipids and DNA
      was found to be markedly increased in AT patients. These results indicate that
      ATM might play an important role in the maintenance of cell homeostasis in
      response to oxidative damage. In this context, a better control of levels of
      reactive oxygen species could be a rational foundation of therapeutic
      intervention to help alleviate some of the symptoms associated with AT.

PMID- 12215215
TI  - Redox control of protein tyrosine phosphorylation.

PMID- 12215214
TI  - Redox events in HTLV-1 Tax-induced apoptotic T-cell death.
AB  - A number of studies implicate reactive oxygen intermediates in the induction of
      DNA damage and apoptosis. Recent studies suggest that the human T-cell leukemia
      virus type 1 (HTLV-1) Tax protein induces oxidative stress and apoptotic T-cell
      death. Activation of the T-cell receptor/CD3 pathway enhances the Tax-mediated
      oxidative and apoptotic effects. Tax-mediated apoptosis and oxidative stress as
      well as activation of nuclear factor-kappaB can be potently suppressed by
      antioxidants. This review focuses on Tax-dependent changes in the intracellular
      redox status and their role in Tax-mediated DNA damage and apoptosis. The
      relevance of these observations to HTLV-1 virus-mediated T-cell transformation
      and leukemogenesis are discussed.

PMID- 12215216
TI  - Tyrosine phosphatase CD45 regulates hydrogen peroxide-induced calcium
      mobilization in B cells.
AB  - By taking advantage of established CD45-deficient DT40 cells, the roles of CD45
      in oxidative stress signaling were investigated. Using p-nitrophenyl phosphate as
      substrate, it was found that CD45 constituted nearly 40% of the total protein
      tyrosine phosphatase activity. Almost 90% of the phosphatase activity was rapidly
      inactivated upon hydrogen peroxide treatment. Hydrogen peroxide-induced tyrosine
      phosphorylation of cellular proteins and c-Jun N-terminal kinase activation were
      markedly enhanced in CD45-deficient cells relative to that in its parental cells.
      In comparison, hydrogen peroxide-induced inositol 1,4,5-trisphosphate production
      and Ca(2+) mobilization were impaired in CD45-deficient DT40 cells. However,
      hydrogen peroxide-induced tyrosine phosphorylation of phospholipase Cgamma2
      (PLCgamma2), phosphatidylinositol 3-kinase activity precipitated by anti
      phosphotyrosine antibody, and activation of Bruton's tyrosine kinase appeared
      intact in CD45-deficient DT40 cells. This suggests that CD45 mediates the ability
      of hydrogen peroxide-activated PLCgamma2 to hydrolyze its substrate via a
      mechanism independent of both tyrosine phosphorylation of PLCgamma2 and
      phosphatidylinositol 3-kinase, as well as activation of Bruton's tyrosine kinase.
      Taken together, our observations demonstrated that, in addition to its negative
      regulatory or phosphatase activity, CD45 has a positive role in oxidative stress
      signaling.

PMID- 12215217
TI  - Antiapoptotic action of focal adhesion kinase (FAK) against ionizing radiation.
AB  - Focal adhesion kinase (FAK) has an antiapoptotic role in anchorage-dependent
      cells via an unknown mechanism. To elucidate the role of FAK in the
      antiapoptosis, we have demonstrated that FAK-overexpressed (HL-60/FAK) cells have
      marked resistance against various apoptotic stimuli. That is, HL-60/FAK cells
      were highly resistant to hydrogen peroxide or etoposide-induced apoptosis
      compared with the vector-transfected cells. In this study, we demonstrated that
      HL-60/FAK cells were highly resistant to ionizing radiation (IR)-induced
      apoptosis. IR at 10-40 Gy induced significant DNA fragmentation, activation of
      caspase-3 and -8, the processing of a proapoptotic BID, and mitochondrial release
      of cytochrome c in the parental or HL-60/Vect cells, whereas no significant DNA
      fragmentation or no other concurring events were observed in the HL-60/FAK cells.
      Of note is that, in the HL-60/FAK cells, phosphatidylinositol 3'-kinase-Akt
      survival pathway was activated, accompanied with significant induction of
      inhibitor-of-apoptosis proteins (cIAP-2, XIAP). Finally, constructs of FAK
      mutants revealed that the central kinase domain (K454), autophosphorylation site
      (Y397), as well as focal adhesion target regions (Y925), were prerequisite for
      the FAK function. These results indicated that mitochondria pathway is required
      for IR-induced apoptosis, and FAK overexpression prevents this pathway, thus
      rendering antiapoptotic states.

PMID- 12215218
TI  - Hypochlorous acid activates tyrosine phosphorylation signal pathways leading to
      calcium signaling and TNFalpha production.
AB  - Hypochlorous acid is an important oxidizing agent produced by neutrophils to aid
      in defense against pathogens. Although hypochlorous acid is known to cause tissue
      damage due to its cytotoxicity, the effect of this oxidizing agent on signal
      transduction by cells of the immune system and its effects on their responses are
      not well understood. In this study, hypochlorous acid was found to induce
      cellular tyrosine phosphorylation in both T and B lymphocytes, activate the ZAP
      70 tyrosine kinase, and induce cellular calcium signaling in a tyrosine kinase
      dependent manner. These signaling events also occurred in T cell lines that did
      not express the T-cell receptor, indicating the ability of hypochlorous acid to
      bypass normal receptor control. Hypochlorous acid induced tumor necrosis factor
      alpha production in peripheral blood mononuclear cells in a tyrosine kinase
      dependent manner. These results suggest that hypochlorous acid may contribute to
      inflammatory responses by activating signal pathways in cells of the immune
      system.

PMID- 12215219
TI  - Syk is required for p38 activation and G2/M arrest in B cells exposed to
      oxidative stress.
AB  - Syk has been demonstrated to play a crucial role in oxidative stress signaling in
      B cells. In this study, we have investigated the role of Syk in p38 activation
      and the regulation of cell-cycle progression upon oxidative stress. In B cells,
      p38 is activated by hydrogen peroxide (H(2)O(2)) stimulation. Syk is required for
      p38 activation following stimulation with 10-100 microM H(2)O(2), but not with 1
      mM H(2)O(2). H(2)O(2)-induced p38 activation is abrogated in phospholipase C
      gamma2 (PLC-gamma2)-deficient as well as Syk-deficient cells, suggesting that Syk
      activates p38 through PLC-gamma2 upon H(2)O(2) stimulation. Although stimulation
      with 20-100 microM H(2)O(2) induces cellular apoptosis in B cells, pretreatment
      with SB203580, a p38-specific inhibitor, has no effect on H(2)O(2)-induced
      apoptosis. Flow cytometric analysis reveals that B cells exposed to 10-20 microM
      H(2)O(2) exhibit cell-cycle profile of G2/M arrest, and pretreatment with
      SB203580 inhibits only a little H(2)O(2)-induced G2/M arrest. On the other hand,
      Syk-deficient cells show no induction of G2/M arrest following H(2)O(2)
      stimulation. These findings indicate that Syk plays a role in the regulation of
      cell-cycle progression in G2/M phase via p38-dependent and -independent pathways
      after oxidative stress.

PMID- 12215220
TI  - Redox-linked signal transduction pathways for protein tyrosine kinase activation.
AB  - The signaling for activation of protein tyrosine kinases (PTKs) is usually
      started by binding of ligands to cell-surface receptors. However, recent evidence
      suggests the presence of ligand binding-independent signaling pathways that are
      mediated by oxidative stress. Oxidation and reduction of protein cysteine
      sulfhydryl (SH) groups may work as a molecular switch to start or to stop the
      signaling. It is known that oxidation of cysteine SH groups on protein tyrosine
      phosphatases switches off the action of protein tyrosine phosphatases. This event
      may not, however, signal for initial autophosphorylation of previously
      unphosphorylated PTKs, whereas it certainly prevents dephosphorylation of once
      phosphorylated PTKs. We have suggested new mechanisms for oxidative stress
      mediated PTK activation. First, cell-surface glycosylphosphatidylinositol
      anchoring proteins and a phosphoglycolipid/cholesterol-enriched membrane
      microdomain termed a "raft" can be the direct targets of oxidative stress for
      inducing their clustering through an S-S-bonded or S-X-S-bonded crosslinking of
      cell-surface proteins and subsequent activation of raft-associating Src family
      PTKs. Second, intracellular specific cysteine SH groups on PTK proteins can be
      another target of oxidative stress for inducing a conformational change necessary
      for initial activation of PTKs. A possible relationship between cell-surface and
      intracellular events is that the former frequently induces superoxide production
      as the second messenger for the latter.

PMID- 12215221
TI  - Role of protein-tyrosine kinase syk in oxidative stress signaling in B cells.
AB  - Oxidative stress induces the activation of multiple signaling pathways related to
      various cellular responses. In B cells, Syk has a crucial role in intracellular
      signal transduction induced by oxidative stress as well as antigen receptor
      engagement. Treatment of B cells with hydrogen peroxide (H(2)O(2)) induces
      enzymatic activation of Syk. Syk is essential for Ca(2+) release from
      intracellular pools through phospholipase C-gamma2 and the activation of c-Jun N
      terminal kinase, p38 mitogen-activated protein kinase, and phosphatidylinositol 3
      kinase-Akt survival pathway following H(2)O(2) stimulation. Oxidative stress
      induced cellular responses in B cells follow different patterns, such as
      necrosis, apoptosis, and mitotic arrest, according to the intensity of H(2)O(2)
      stimulation. Syk is involved in the protection of cells from apoptosis and
      induction of G2/M arrest. Syk leads to the activation of the phosphatidylinositol
      3-kinase-Akt survival pathway, thereby enhancing cellular resistance to oxidative
      stress-induced apoptosis. On the other hand, Syk-dependent phospholipase C-gamma2
      activation is required for acceleration toward apoptosis following oxidative
      stress. These findings suggest that oxidative stress-induced Syk activation
      triggers the activation of several pathways, such as proapoptotic and survival
      pathways, and the balance among these various pathways is a key factor in
      determining the fate of a cell exposed to oxidative stress.

PMID- 12215222
TI  - Oxidants and tyrosine phosphorylation: role of acute and chronic oxidative stress
      in T-and B-lymphocyte signaling.
AB  - The cellular response to an extracellular signal starts with the induction of a
      signaling cascade that transmits the signal through the cytoplasm to the nucleus,
      resulting in the activation of transcription factors that activate specific
      target genes. The signaling cascade involves a series of biochemical
      modifications that include phosphorylation events on tyrosine residues due to the
      activation of specific protein kinases. Recently, evidence accumulated that
      reactive oxygen species, including hydrogen peroxide, superoxide, and the
      hydroxyl radical, are important chemical mediators that regulate the transduction
      of signals from the membrane to the nucleus by modulating the protein activity by
      oxidation and reduction. In this report, the redox regulation of signaling
      involving protein tyrosine kinase activity, in particular in T- and B-lymphocyte
      signaling, is reviewed.

PMID- 12215223
TI  - Dihydrolipoic acid as an effective cofactor for peptide methionine sulfoxide
      reductase in enzymatic repair of oxidative damage to both lipid-free and lipid
      bound apolipoprotein a-I.
AB  - The aim of this study was to examine the possible use of dihydrolipoic acid
      (DHLA), the reduced form of lipoic acid, in the reduction of oxidized
      apolipoprotein A-I mediated by peptide methionine sulfoxide reductase (PMSR), and
      to test the accessibility of methionine sulfoxides in the lipid-bound oxidized
      apolipoprotein A-I to this reaction. We show that DHLA acts as an effective
      cofactor for PMSR, mediating restoration of the native secondary structure,
      tertiary structure, stability, and lipid-binding properties of the native
      unoxidized protein. Reconstituted high-density lipoproteins were used to
      demonstrate effective enzymatic reduction of the lipid-bound oxidized protein in
      the presence of DHLA. These findings suggest that the enzymatic repair of
      oxidative damage to intact lipoproteins could provide a model of a possible
      repair mechanism active in vivo during oxidative stress and that the restoration
      of high-density lipoprotein function could be one of the therapeutic benefits of
      lipoic acid.

PMID- 12215224
TI  - Ethical standards for authors, and for the Journal of Amyotrophic Lateral
      Sclerosis and other motor neuron diseases.

PMID- 12215225
TI  - What have cellular models taught us about ALS?

PMID- 12215226
TI  - Impaired oxidative metabolism and lipid peroxidation in exercising muscle from
      ALS patients.
AB  - BACKGROUND: Although the pathogenic mechanisms of selective loss of motor neurons
      in amyotrophic lateral sclerosis (ALS) are unknown, there is increasing evidence
      for the hypothesis of an oxidative stress-related mitochondrial involvement as
      key determinant of motor neuron degeneration OBJECTIVE: The aim of our study has
      been to assess blood levels of peroxidation markers and to relate them to in-vivo
      oxidative metabolism in exercising muscle in patients affected by ALS. METHOD:
      For this purpose 10 patients (seven men and three women, mean age 58.5 +/- 8.2
      SD), performed an incremental bicycling test for the assessment of lipoperoxides
      and lactate during exercise. RESULTS: At rest, the ALS patients had higher than
      normal levels of both lactate (2.82 +/- 0.76 mmol/L; normal range: 0.67-2.47
      mmol/L) and lipoperoxides (361.7 +/- 40.2 AU; normal range: 250-320 AU), the
      latter corresponding to a level of moderate oxidative stress. A further increment
      during exercise was observed both at lactate threshold and maximal power output
      levels. Values of blood lipoperoxides were significantly higher (P < 0.05) than
      those in control patients affected by chronic motor denervating processes of
      different origins and related (P < 0.01) to lactate production on exercising.
      CONCLUSIONS: These findings indicate the occurrence of an abnormally increased
      size of blood free radical pool in resting conditions and during exercise in ALS
      patients. The relationship between the levels of reactive oxygen species and
      lactate production is indicative of a tight link between mitochondrial function
      and oxidative stress in ALS.

PMID- 12215227
TI  - Detection of N epsilon-(carboxymethyl)lysine (CML) and non-CML advanced glycation
      end-products in the anterior horn of amyotrophic lateral sclerosis spinal cord.
AB  - INTRODUCTION: The involvement of glycation in neurodegenerative diseases such as
      Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS)
      was recently indicated. We previously reported the existence of an Amadori
      product, 1-hexitol-lysine (1-HL), which is formed in the early glycation
      reaction, in axonal spheroids of the anterior horn of the ALS spinal cord.
      OBJECTIVE: The purpose of the present study was to confirm the occurrence of the
      later-stage glycation reaction that follows the early glycation reaction and
      leads to the formation of advanced glycation end products (AGEs). METHOD: We
      examined whether N(epsilon)-(carboxymethyl)lysine (CML) and non-CML AGE are
      present in ALS spinal cords. RESULTS: Immunohistochemical staining with anti-CML
      antibody revealed intense positivity in the cell bodies of the remaining atrophic
      motor neurons and in microglia. Microglia were also positive on staining with
      anti-non-CML antibody. Axonal spheroids were also positive on anti-non-CML
      antibody staining. Vascular endothelial cells were slightly stained by both
      antibodies. CONCLUSIONS: The presence of non-CML AGE in the anterior horn of the
      ALS spinal cord indicates that the later stage of the glycation reaction is
      involved in the pathology of ALS. The presence of CML in the anterior horn was
      also confirmed, and this may reflect augmented oxidative stress.

PMID- 12215228
TI  - A novel exon 3 mutation (D76V) in the SOD1 gene associated with slowly
      progressive ALS.
AB  - INTRODUCTION: Details of the mutations in the Cu/Zn superoxide dismutase (SOD1)
      gene in patients with the familial form of amyotrophic lateral sclerosis are
      currently being gathered in order better to understand the genotype-phenotype
      relationship in this disorder. We report on a large family with 15 affected
      individuals spanning five generations. RESULTS: A novel mutation in the exon 3 of
      the SOD1 gene, an A-to-T transversion at nucleotide position 696 in the
      heterozygous state leading to a D76V amino acid change, was identified in four
      family members. Affected individuals showed a homogeneous phenotype,
      characterized by initial symptoms in the lower limbs, clinical onset in the fifth
      decade of life, long survival and high penetrance. DISCUSSION: Our results are
      discussed in relation to the previously reported exon 3 SOD1 mutations, paying
      particular attention to the phenotypic characteristics of ALS-SOD1 patients.

PMID- 12215229
TI  - Cu/Zn superoxide dismutase (SOD1) mutations associated with familial amyotrophic
      lateral sclerosis (ALS) affect cellular free radical release in the presence of
      oxidative stress.
AB  - INTRODUCTION: The exact molecular mechanisms by which mutations in Cu/Zn
      superoxide dismutase (SOD1) cause motor neuron injury remain incompletely
      understood, though a body of evidence suggests that the mutant protein exerts a
      cell-specific toxic gain of function. The role of nitric oxide (NO) in SOD1
      related motor neuron injury has been particularly controversial. Theoretically,
      there are arguments to suggest that NO may exert an important role in motor
      neuron injury, but there is relatively little direct experimental support for
      this hypothesis. OBJECTIVES: The present study aimed to examine further the
      potential role for NO in motor neuron injury caused by mutant SOD1. METHOD: We
      have generated a cellular model of familial amyotrophic lateral sclerosis (ALS)
      by stably transfecting NSC34 cells with one of three mutant forms of SOD1 (G93A,
      G37R, I113T). In the presence of mutant SOD1, NSC34 cells show increased cell
      death following oxidative stress induced by serum withdrawal. This model of motor
      neuron death involves cellular release of superoxide and NO radicals, which were
      directly measured in real time using microelectrode biosensors. RESULTS: The
      expression of both normal and mutant SOD1 decreased the measured extracellular
      superoxide release, but had divergent effects on the measured release of NO.
      Normal SOD1 increased the measured NO release, whereas cells expressing mutant
      SOD1 released less NO. Co-administration of two different nitric oxide synthase
      inhibitors (L-NAME and L-N-methyl arginine) did show some neuroprotective effect,
      but this was only partial, and the effect was more marked using nuclear integrity
      as a measure of cell viability, rather than MTT conversion. Cells expressing
      mutant SOD1 were, however, more sensitive to toxicity induced by extrinsic
      exposure to NO, using a slow-release NO donor. CONCLUSION: NO is likely to
      contribute to motor neuron injury, but this does not fully account for all the
      cellular toxic effects of mutant SOD1.

PMID- 12215230
TI  - Spinal muscular atrophy: state-of-the-art and therapeutic perspectives.
AB  - Proximal spinal muscular atrophy (SMA) is a common autosomal recessive disorder
      in humans caused by degeneration of alpha motor neurons in the anterior horns of
      the spinal cord. This affects voluntary movements, leading to muscle weakness and
      atrophy. SMA is caused by homozygous deletions/mutations in the survival motor
      neuron gene 1 (SMN1). The severity of the phenotype is modulated by the copy
      number of SMN2 and by other yet unknown factors. SMN2 is affected by a critical
      non-translational nucleotide exchange in exon 7 that disrupts an exonic splicing
      enhancer. In consequence SMN2 produces mainly alternatively spliced mRNA that
      lacks exon 7. Trans-activating factors such as Htra2-beta1, as well as various
      drugs like sodium butyrate or aclarubicin, are able to restore the full-length
      SMN2 RNA to large amounts. Since each SMA patient carries at least one SMN2 copy,
      reconstitution of full-length SMN2 protein is an exciting strategy for somatic
      gene therapy in SMA patients.

PMID- 12215232
TI  - Non-replication of genetic association studies: is DAT all, folks?

PMID- 12215233
TI  - DAT's not all, but it may be more than we realize.

PMID- 12215234
TI  - Modulating tobacco smoking rates by dopaminergic stimulation and blockade.
AB  - This study was designed to demonstrate that dopaminergic stimulation would result
      in decreased smoking behavior and nicotine intake, whereas dopaminergic blockade
      would result in increased smoking behavior and nicotine intake, in the same
      subjects. In prior human studies, a dopaminergic antagonist, haloperidol,
      increased smoking and/or nicotine intake, and a dopamine agonist, bromocriptine,
      decreased smoking. The smoking behavior of 20 heavy smokers was observed on two
      separate visits in a randomized, double-blind, repeated-measures-within-subject
      design. In the drug-reversal design, either bromocriptine (2.5 mg) or haloperidol
      (2.0 mg) was administered at each 5-h session, during which subjects smoked their
      own cigarettes ad libitum. Smoking topography was measured using a thermistor
      flow detector apparatus. Subjects smoked their cigarettes faster (p<0.05) and
      total puffing time was greater (p<0.05) with haloperidol than with bromocriptine.
      There was a trend for both a shorter latency to smoke (p<0.10, one-tailed) during
      time of expected peak drug concentration and for a shorter inter-cigarette
      interval with haloperidol than with bromocriptine (p<0.10, one-tailed). Shiffman
      Jarvik Withdrawal Scale craving subscale scores increased significantly more with
      haloperidol than with bromocriptine (p<0.05). Mean Profile of Mood States (POMS)
      scores differed significantly for only one subscale (Confusion:
      bromocriptine>haloperidol; p<0.05). These data support the hypothesis that
      nicotine mediates reinforcement from smoking via dopamine, and that smoking
      behavior can be manipulated within the same subjects in opposite directions by
      alternately stimulating and blocking dopamine.

PMID- 12215235
TI  - Bupropion for the treatment of nicotine dependence in spit tobacco users: a pilot
      study.
AB  - Few pharmacological therapies have been shown to increase abstinence rates among
      spit tobacco (ST) users. Bupropion has been shown to be effective in increasing
      abstinence rates among smokers but has not been studied in ST users. Sixty-eight
      adult (aged > or = 18 years old) regular users of ST who were motivated to stop
      using ST were enrolled in a randomized, double-blind, placebo-controlled pilot
      study of bupropion sustained release (SR) or placebo for 12 weeks. The primary
      endpoint was 1-week, biochemically confirmed point-prevalence tobacco abstinence
      rate at the end of treatment (week 12). Nicotine withdrawal symptoms and weight
      change were assessed. At the end of 12 weeks of therapy, the point-prevalence
      tobacco abstinence rate was 44% in the bupropion group and 26% in the placebo
      group (p = 0.064). At 24 weeks following initiation of medication, the point
      prevalence abstinence rate was 29% for both groups. After 7 weeks of medication,
      subjects on bupropion reported significantly less (p< or = 0.034) nicotine
      withdrawal than placebo. The mean weight change from baseline to end of treatment
      was +0.7 +/- 1.9 kg for bupropion and +4.4 +/- 2.4 kg for placebo (p = 0.03). The
      6-month weight change for continuously abstinent subjects was 3.4 +/- 3.6 kg in
      the bupropion group and 6.2 +/- 5.0 kg in the placebo group (p = 0.49). Bupropion
      may increase abstinence rates in ST users and appears to attenuate weight gain
      during ST abstinence. Larger randomized, controlled trials of bupropion for ST
      users are needed.

PMID- 12215236
TI  - Effects of a low dose of transdermal nicotine on information processing.
AB  - The objective of this research was to assess the effect of a low dose of nicotine
      (7 mg/24 h), administered through a transdermal device, on the cognitive
      processes of subjects who were slightly dependent smokers. Sixteen smokers were
      chosen as subjects using a French version of Fagerstrom's Test of Nicotine
      Dependence. Under suboptimal alertness conditions the subjects were faced with a
      choice reaction time (CRT) task. Two conditions of signal quality (intact or
      degraded) and two conditions of fore period (FP) (short or long) were used during
      two different experimental sessions (nicotine or placebo). At the same time, the
      subjects filled in a mood questionnaire and took part in a critical flicker
      fusion (CFF) determination test. The results obtained suggest that nicotine
      improves the subjective state of alertness of the subjects and enables them,
      despite the suboptimal state, to maintain a constant performance level during a
      CRT task. Neither an effect of nicotine on the CFF nor any interaction between
      the nicotine, the signal quality or the duration of the FP were observed. The
      conclusion to be drawn from the results is that nicotine has an enabling effect,
      but the results do not allow the determination of the precise site of this effect
      among the different stages of information processing.

PMID- 12215237
TI  - Relations of cotinine and carbon monoxide to self-reported smoking in a cohort of
      smokers and ex-smokers followed over 5 years.
AB  - We describe the persistence of discrepancies between biochemical measures of
      smoking and self-reported smoking status in a cohort of clinical trial
      participants across 5 years. The Lung Health Study, a randomized trial in 10
      clinical centers in North America, enrolled 3923 participants in smoking
      intervention and 1964 in usual care in 1987 and 1988. Smoking status was assessed
      at baseline and at five annual follow-up visits by self-report, salivary cotinine
      and expired-air carbon monoxide. Compared to self-report, sensitivity and
      specificity of cotinine and carbon monoxide were similar across 5 years. Evidence
      of error in self-reports of quitting smoking persisted across 5 years, although
      it declined over time. Multivariate models confirmed that self-report bias was
      characteristic of the early years in the study. Significant covariates differed
      between cotinine and carbon monoxide models. When cotinine was used for
      verification, about half of the individuals in the smoking intervention group
      with self-report bias at the first year continued to exhibit bias for 5 years. In
      absolute terms, the errors associated with measurement were small, but they
      persisted over 5 years. Some differences appeared to be related to the
      distinction that carbon monoxide verification was immediate, while cotinine
      verification was deferred.

PMID- 12215238
TI  - Discounting of delayed health gains and losses by current, never- and ex-smokers
      of cigarettes.
AB  - Recent evidence implicates steep discounting of delayed outcomes as an important
      feature of drug dependence. We determined discounting rates for health gains and
      health losses in current cigarette smokers (n = 23), never-smokers (n = 22) and
      ex-smokers (n = 21). Participants indicated preference for immediate vs. delayed
      hypothetical health gains and for immediate vs. delayed hypothetical health
      losses in a titration procedure that determined indifference points at a range of
      delays. The degree of discounting was estimated using two nonlinear decay models:
      an exponential model and a hyperbolic model. The hyperbolic equation generally
      provided better fits to the data than the exponential equation did. Current
      smokers discounted delayed health gains and health losses more steeply than never
      smokers did. Discounting by ex-smokers was generally intermediate to that of
      current smokers and never-smokers, although not statistically different from
      either. Current smokers and ex-smokers discounted delayed health losses more
      steeply than they did health gains. Never-smokers did not discount gains and
      losses differently. Cigarette smokers show rapid loss of value for delayed health
      outcomes, emphasizing the need for smoking-cessation treatments that provide
      relatively immediate consequences for abstinence.

PMID- 12215239
TI  - The accuracy of self-reported smoking status assessed by cotinine test strips.
AB  - We evaluated a new cotinine test strip to assess smoking status. Urine cotinine
      was measured using cotinine test strips and also by gas chromatographic
      techniques (GC) (as the reference criterion). Smoking status was assessed with a
      self-administered questionnaire. The cotinine test strip identified smokers with
      a very high level of agreement (97.3% using 100 ng/ml and 97.1% using 250 ng/ml
      for the cutoff point) and non-smokers with a fair-to-moderate level of agreement
      (74.5% using 100 ng/ml and 86.4% using 250 ng/ml for the cutoff point). These
      data suggest that the cotinine test strip appears to provide a reasonably
      accurate measure of smoking status. Since this was the first study to evaluate
      the cotinine test strip using the test strip prototype, larger clinical trials
      are needed to evaluate the validity of the cotinine test strip compared to GC
      measurements to confirm smoking status.

PMID- 12215240
TI  - Global and regional estimates of the effectiveness and cost-effectiveness of
      price increases and other tobacco control policies.
AB  - The objective of this study was to provide conservative estimates of the global
      and regional effectiveness and cost-effectiveness of tobacco control policies.
      Using a static model of the cohort of smokers alive in 1995, we estimated the
      number of smoking-attributable deaths that could be averted by: (1) price
      increases, (2) nicotine replacement therapy (NRT), and (3) a package of non-price
      interventions other than NRT. We calculated the cost-effectiveness of these
      policy interventions by weighing the approximate public-sector costs against the
      years of healthy life saved, measured in disability-adjusted life years, or
      DALYs. Even with deliberately conservative assumptions, tax increases that would
      raise the real price of cigarettes by 10% worldwide would prevent between 5 and
      16 million tobacco-related deaths, and could cost 3-70 US dollars per DALY saved
      in low-income and middle-income regions. NRT and a package of non-price
      interventions other than NRT are also cost-effective in low-income and middle
      income regions, at 280-870 US dollars per DALY and 36-710 US dollars per DALY,
      respectively. In high-income countries, price increases were found to have a cost
      effectiveness of 83-2771 US dollars per DALY, NRT 750-7206 US dollars per DALY
      and other non-price interventions 696-13,924 US dollars per DALY. Tobacco control
      policies, particularly tax increases on cigarettes, are cost-effective relative
      to other health interventions. Our estimates are subject to considerable
      variation in actual settings; thus, local cost-effectiveness studies are required
      to guide local policy.

PMID- 12215241
TI  - Smoking cessation during the transition from adolescence to young adulthood.
AB  - The psychosocial and behavioral determinants of smoking cessation from late
      adolescence to early adulthood were investigated in a sample of 711 individuals
      followed from 1990 (grade 12) to 1995. Analyses stratified by sex indicated that
      female smokers were more likely to quit 5 years later if they had fewer friends
      who smoked, less parental approval of their smoking, weaker intentions to
      continue smoking, higher smoking resistance self-efficacy and better grades at
      grade 12. Several of these associations could be accounted for by smoking
      quantity. Similar analyses for male smokers indicated that those who eventually
      quit were more likely to have fewer cigarette offers, weaker intentions to smoke,
      better grades and an intact nuclear family at grade 12. The associations for
      males could not be explained by smoking quantity. Interaction analyses showed few
      significant sex differences in the predictors of smoking cessation. Results
      suggest that cessation programs should continue to target parental and peer
      influences, as well as skills at resisting social influences to smoke, through
      late adolescence, but do not indicate that such programs need to be adapted to
      the special needs of male and female smokers.

PMID- 12215242
TI  - Smoking status and the human dopamine transporter variable number of tandem
      repeats (VNTR) polymorphism: failure to replicate and finding that never-smokers
      may be different.
AB  - Cigarette smoking, like many addictive behaviors, has been shown to have a
      genetic component. The dopamine transporter (DAT) gene (SLC6A3) encodes a protein
      that regulates synaptic levels of dopamine in the brain and is a candidate gene
      for addictive behaviors. We have collected smoking information from a national
      probability sample of 3383 adult volunteers contacted via a random-digit dialing
      telephone interview. A subset of individuals provided DNA from cheek swabs
      returned via the mail for subsequent genetic analysis of self-reported smoking
      behavior. DNA samples were genotyped at a variable number of tandem repeats
      (VNTR) polymorphism in the 3'-untranslated region of the DAT gene. If we classify
      smokers as non- (<100 cigarettes), former and current, we fail to replicate both
      Lerman et al. (Health Psychology 18:14-20, 1999) and Sabol et al. (Health
      Psychology 18:7-13, 1999) and support the absence of effects found by Jorm et al.
      (American Journal of Medical Genetics (Neuropsychiatric Genetics) 96:331-334,
      2000). When we distinguish between never-smokers (no cigarettes ever) and non
      smokers (1-99 in lifetime), we find a reliable trend essentially in the opposite
      direction from Lerman et al. (1999), with the 10-copy allele being more frequent
      in never-smokers. Biobehavioral research on cigarette smoking should distinguish
      between never- and non-smokers. We have also developed an improved set of
      polymerase chain reaction conditions to increase the frequency of successful
      amplification of DAT'sw VNTR, which is a long, G+C-rich repeat.

PMID- 12215243
TI  - The role of nitric oxide in cigarette smoking and nicotine addiction.
AB  - The purpose of this study is to describe the interrelationship between nitric
      oxide (NO) and nicotine in cigarette smoking addiction, in view of the underlying
      hypothesis that NO contributes to smoking (nicotine) addiction, and to suggest
      the ways to improve prevention as well as cessation strategies. A literature
      search of Medline using the keywords nicotine and nitric oxide covering 1995 to
      May 2001 was made. Further information not obtained from the Medline search was
      derived from the references cited in these publications. Smokers are exposed
      first to high concentrations of inhaled NO from smoke and, second, to
      endogenously released NO after uptake of nicotine into the brain. As a result,
      the basal endogenous NO synthesis in airways and blood vessels of smokers is
      reduced. Subsequently, because NO is involved in maintaining airway dilatation,
      smokers may have constricted airways. During smoking, however, NO from smoke may
      dilate the constricted airways, allowing the smoke an easier passage into the
      lungs, and exposing the body and the brain to more nicotine. NO can endogenously
      be released by nicotine from nervous tissue, and may decrease the sympathetic
      output of the brain, which is associated with stress reduction. This second form
      of exposure to NO also inhibits the re-uptake of dopamine, which may contribute
      to dopaminergic receptor stimulation and thus to the acute rewarding effects of
      nicotine. The important role of NO in nicotine addiction is further supported by
      the finding that in animals NO synthase (NOS) inhibitors attenuate symptoms of
      the nicotine abstinence syndrome. NO may contribute to the development of
      cigarette smoking and nicotine addiction since: (1) inhaled NO from smoke may be
      able to increase nicotine absorption, (2) NO released through nicotine reduces
      symptoms of stress, (3) NO endogenously released by nicotine increases post
      synaptic dopamine levels, and (4) NOS inhibitors attenuate symptoms of the
      nicotine abstinence syndrome. It remains to be determined whether reducing the NO
      content in cigarette smoke may reduce nicotine absorption. It also needs to be
      clarified whether NOS inhibitors or a low L-arginine diet might be useful in the
      treatment of nicotine addiction.

PMID- 12215244
TI  - Can stopping smoking cause hypertension?

PMID- 12215245
TI  - Progress in nicotine and tobacco research.
AB  - The Eighth Annual Meeting of the Society for Research on Nicotine and Tobacco
      (SRNT) was held in Savannah, Georgia, on 21-23 February 2002. This meeting was
      the largest to date, with more than 600 registered attendees, five outstanding
      plenary speakers, 10 symposia, six oral paper sessions, and four filled-to
      capacity poster sessions. The meeting content represented three major areas of
      SRNT's emphasis: Preclinical, Epidemiology/Public Health and Clinical research;
      thus the meeting was an outstanding opportunity to share with, and learn from,
      colleagues engaged in the full spectrum of nicotine and tobacco research.
      Additional events included pre- and post-meeting symposia, a career development
      question-and-answer workshop, a global network interest meeting, and a variety of
      awards. SRNT also remembered and honored the lives and work of two outstanding
      colleagues who were lost to the society over the past year: Dr. Chris Silagy and
      Dr. John Slade. Highly significant and innovative research continues in the field
      of nicotine and tobacco, and this innovation and significance was readily
      apparent in the science presented at the eighth annual meeting.

PMID- 12215246
TI  - Genetic testing for women previously diagnosed with breast/ovarian cancer:
      examining the impact of BRCA1 and BRCA2 mutation searching.
AB  - This study sought to investigate the impact of BRCA1 and BRCA2 mutation searching
      on women previously diagnosed with breast or ovarian cancer. In-depth interviews
      were undertaken with 30 women who had undergone a BRCA1 and BRCA2 mutation search
      within the clinical setting. The main reasons reported for undergoing mutation
      searching were: to provide genetic information for other family members, general
      altruism, curiosity about the aetiology of cancer, and to provide information to
      facilitate risk management decisions. In the main, the process of undergoing
      genetic testing was not experienced as anxiety provoking. The benefit of
      receiving a result confirming the presence of a genetic mutation was seen as an
      end to uncertainty, whereas the costs included difficulties in disclosing
      information to kin and potentially increased anxiety about one's own or others'
      cancer risks. Women receiving an inconclusive test result reported a range of
      emotional reactions. There was evidence that some women misunderstood the meaning
      of this result, interpreting it as definitive confirmation that a cancer
      predisposing mutation was not present within the family. It is concluded that
      women with cancer who participate in BRCA1 and BRCA2 testing need to receive
      clear information about the meaning and implications of the different types of
      test results. Some recommendations for clinical practice are discussed.

PMID- 12215247
TI  - Voluntary disclosure of BRCA1 mutation test results.
AB  - This study assessed the probability that individuals tested for a BRCA1 gene
      mutation share their test results with family members, co-workers, and insurers.
      Members of a large kindred known to be at-risk for carrying a BRCA1 gene mutation
      were tested and they learned their results from a genetic counselor. During a
      follow-up interview, 4 months later, subjects were asked with whom they had
      shared their results. Respondents were most likely to have communicated results
      to family members, followed by co-workers, and insurers. Carrier status affected
      their willingness to disclose results to insurers. High rates of disclosure to
      family members should promote awareness of hereditary cancer risk. Selective
      disclosure to co-workers and insurers may promote information asymmetries that
      could affect employment and insurance markets.

PMID- 12215248
TI  - Pre-counseling education materials for BRCA testing: does tailoring make a
      difference?
AB  - Although tailored print materials (TPMs) have been assessed for a variety of
      behavioral targets, their effectiveness as decision aids for genetic testing had
      not been evaluated at the time this study began. We compared TPMs and non
      tailored print material (NPMs) that included similar content about genetic
      testing for breast and ovarian cancer susceptibility. TPMs were prepared
      especially for an individual based on information from and about her. We mailed
      baseline surveys to 461 women referred by physicians or identified through a
      tumor registry. All had personal and family histories of breast and/or ovarian
      cancer and, on the basis of these histories, an estimated > or =10% probability
      of carrying a mutation in the breast/ovarian cancer genes BRCA1 or BRCA2. The 325
      (70%) who responded were randomly assigned to receive TPM or NPM. Followup
      surveys, mailed 2 weeks following receipt of print materials, were returned by
      262 women (81% of baseline responders). Participants were predominately white
      (94%) and well-educated (50% college graduates). The mean age was 49 years. At
      follow-up, TPM recipients exhibited significantly greater improvement in percent
      of correct responses for the 13-item true/false measure of knowledge (24%
      increase for TPM vs. 16% for NPM; p < 0.0001) and significantly less over
      estimation of risk of being a mutation carrier (40% TPM group overestimated vs.
      70% NPM; p < 0.0001). Anxiety did not differ significantly between groups.
      Reactions to materials differed on two items: "seemed to be prepared just for me"
      (76% TPM vs. 52% NPM; p < 0.001) and "told me what I wanted to know about BRCA1
      and 2 testing" (98% TPM vs. 91% NPM; p < 0.05). TPMs showed an advantage in
      increasing knowledge and enhancing accuracy of perceived risk. Both are critical
      components of informed decision making.

PMID- 12215249
TI  - Clinical interpretation and recommendations for patients with a variant of
      uncertain significance in BRCA1 or BRCA2: a survey of genetic counseling
      practice.
AB  - The intent of this study was to document current practices in breast cancer
      genetic counseling and identify areas of variability for patients with a variant
      of uncertain significance (VUS) in the BRCA1 or BRCA2 gene. Registered members of
      the National Society of Genetic Counselors (NSGC) Cancer Special Interest Group
      (SIG) were sent an invitation via electronic mail to participate in an online
      questionnaire. The questionnaire was divided into three sections: clinical
      experience, clinical meaning, and risk perceptions and clinical recommendations
      for clinical situations involving a VUS. Fifty-seven of the eligible members
      responded. During the pre-test counseling session for a BRCA risk assessment
      patient, the vast majority of counselors (80.7%) mention VUS as a possible test
      result. Nearly half, 49.1%, report having given such a result to their patients
      at least one to four times. However, only 63.2% felt as though their patients
      understood the meaning of a VUS result. When asked to conclude the implication of
      a VUS and make medical management recommendations, the responses were varied.
      Nevertheless, a good proportion of counselors expressed the importance of testing
      other family members to help clarify the proband's risk and aid in medical
      management issues. Although the recent recommendations by the American College of
      Medical Genetics suggest standards for the interpretation of sequence variations,
      they do not provide guidelines for making clinical recommendations based on these
      variations. The results of this study reveal significant diversity in the
      personal interpretation of a VUS result, leading to various clinical
      recommendations, and suggest a need for clinical management recommendations as
      well.

PMID- 12215250
TI  - What does my doctor think? Preferences for knowing the doctor's opinion among
      women considering clinical testing for BRCA1/2 mutations.
AB  - The traditional emphasis on nondirectiveness in genetic counseling has become
      increasingly controversial with the rapid expansion of genetic testing in
      clinical medicine. This study was done to determine whether women considering
      clinical testing for BRCA1/2 mutations want to know their health care providers'
      opinions about whether or not they should undergo testing. Participating in the
      study was a retrospective cohort of 335 women who participated in a university
      based clinic offering breast cancer risk assessment, genetic counseling, and
      BRCA1/2 testing between January, 1996, and April, 1998. A total of 242 women
      (77%) wanted to know if the doctors at the Breast and Ovarian Cancer Risk
      Evaluation Program (BCREP) thought they should be tested, 28 women (9%) were
      unsure, and 46 women (14%) did not want a BCREP doctor's opinion on testing. A
      total of 158 women (49%) wanted to know if their primary doctor thought they
      should be tested, 31 women (10%) were unsure, and 130 women (41%) did not want to
      know. Desire to know the opinion of the BCREP doctors was inversely associated
      with having undergone BRCA1/2 testing (RR 0.83, 95% CI 0.73-0.95) and having a
      breast cancer diagnosis (RR 0.86, 95% CI 0.75-0.99). Desire to know their primary
      doctor's opinion was inversely associated with having undergone BRCA1/2 testing
      (RR 0.72, 95% CI 0.56-0.92). Our study suggests that over three-quarters of women
      who considered clinical testing for BRCA1/2 mutations wanted to know the opinions
      of the cancer genetics doctors and almost half wanted to know their primary
      doctor's opinion about whether or not they should undergo testing. These results
      support the use of models of genetic counseling that allow for sharing the health
      care providers' opinions when desired by the patient.

PMID- 12215251
TI  - Characterization of common BRCA1 and BRCA2 variants.
AB  - Many missense variants identified in BRCA1 and BRCA2, two genes responsible for
      the majority of hereditary breast and ovarian cancer, are of unclear clinical
      significance. Characterizing the significance of such variants is important for
      medical management of patients in whom they are identified. The aim of this study
      was to characterize eight of the most common reported missense mutations in BRCA1
      and BRCA2 occurring in patients tested for hereditary risk of breast and ovarian
      cancers. The prevalence of each variant in a control population, co-segregation
      of the variant with cancer within families, location of the variant within the
      gene, the nature of the amino acid substitution and conservation of the wild-type
      amino acid among species were considered. In a control population, the BRCA1
      variants M1652I, R1347G, and S1512I, were each observed at a frequency of 4.08%,
      2.04%, and 2.04%, respectively, and the BRCA2 variants A2951T, V2728I, and
      D1420Y, were seen at 1.02%, 0.68%, and 0.34%, respectively. Although the BRCA2
      variants T598A and R2034C were not seen in this group of controls, other clinical
      and published observations indicate that these variants are not deleterious.
      Based on epidemiological and biological criteria, we therefore conclude that the
      BRCA1 missense mutations R1347G, S1512I and M1652I, and the BRCA2 missense
      mutations T598A, D1420Y, R2034C, V2728I, and A2951T, are not deleterious
      mutations.

PMID- 12215252
TI  - Frequency of CCR5 Gene 32-bp deletion in Pakistani ethnic groups.
AB  - CCR5 is a G-protein-coupled chemokine receptor that is used as a co-factor by
      macrophage-tropic (M-tropic) isolates of human immunodeficiency virus-1 (HIV-1)
      to gain entry into host cells. A 32-bp deletion in the CCR5 gene (CCR5-Delta32)
      leads to the production of an altered gene product that prevents HIV-1 from
      entering the host cell. This study was carried out to determine prevalence of
      CCR5-Delta32 allele frequency in a large Pakistani population sample (n = 821)
      representing 10 ethnic groups. No individual was homozygous for the mutant allele
      and the frequency of the CCR5-Delta32 allele ranged from 0.62% to 3.57%. The CCR5
      Delta32 allele frequency was generally lower in populations from southern
      Pakistan. The overall frequency of the CCR5-Delta32 allele in Pakistan was 2.31%,
      which is much lower than that found in European populations and similar to that
      in the Middle East. This is consistent with the historical records and genetic
      data that indicate a close genetic affinity among these populations. This study
      demonstrates that the Pakistani population is highly susceptible to M-tropic
      isolates of HIV-1 and public health measures need to be enforced with urgency if
      Pakistan is to avoid an HIV epidemic.

PMID- 12215253
TI  - Angelman syndrome methylation screening of 15q11-q13 in institutionalized
      individuals with severe mental retardation.
AB  - Among several genetic diseases that comprise mental retardation, Angelman
      syndrome (AS) has been extensively recognized and investigated. In the general
      population, the syndrome occurs in about 1 in 20,000 live births and its
      prevalence in severely mentally retarded individuals is 1.4%. These figures,
      however, may be an underestimate, because of the variable phenotype of AS. The
      main objective of this work was to investigate AS patients among a group of
      mentally retarded subjects, using the methylation pattern of the SNRPN gene, as
      determined by Southern blotting molecular analysis. The molecular investigation
      of 75 institutionalized individuals with severe to profound mental retardation
      resulted in the detection of 1 case with an abnormal methylation pattern of the
      SNRPN gene, corresponding to AS. The patient's phenotype was classified as
      atypical, without outbursts of inappropriate laughter or a happy disposition; the
      patient would not have been diagnosed in the usual screens for AS, which only
      select patients who demonstrate the typical clinical findings characteristic of
      the disease.

PMID- 12215254
TI  - Rapid detection of the hypertension-associated A1166C polymorphism of the
      angiotensin II type 1 receptor (AGTR1).
AB  - Screening for polymorphisms in the human type 1 angiotensin II receptor locus
      (AGTR1) has led to the identification of an A1166C transversion in the 3'
      untranslated region. This molecular variant, C(1166), has been linked to
      essential hypertension. We describe here a rapid method for the detection of this
      point mutation by a simple modification of PCR amplification with allele-specific
      oligonucleotides (ASO), so as to avoid a hybridization procedure involving either
      radioactive- or non-radioactive-labeled probes, labeled primers, or restriction
      typing. The procedure described is convenient for routine clinical laboratory use
      with manual sample processing and offers the potential for further automation, as
      well.

PMID- 12215255
TI  - Simple fluorescent PCR assay for discriminating FRAXA fully mutated females from
      normal homozygotes.
AB  - Fragile X syndrome linked to the FRAXA locus is the most common inherited genetic
      disease accounting for mental retardation and is usually caused by the expansion
      of an unstable CGG repeat in the first exon of the FMR1 gene on the X chromosome.
      Despite its robustness, Southern blot is not suitable for large-scale routine
      screening as part of neuropediatric practice. PCR appears as an interesting
      alternative, and various protocols have been successfully applied to molecular
      screening in mentally retarded boys and girls. Unfortunately, as of this date
      these protocols are unable to detect the expanded allele in FRAXA females
      reliably, thereby failing to discriminate between fully mutated females from
      normal homozygotes. Therefore, we opted for an alternative approach in designing
      a semiquantitative PCR assay, based on the amplification of the sole wild-type
      allele. This method allowed us to detect the presence of one or two normal
      alleles with the same sizes, thereby discriminating between a FRAXA fully mutated
      female or a normal homozygote, respectively. A trial on 95 DNA samples from
      normal and mutated females demonstrated the reliability of the procedure. We
      believe this simple PCR assay is a powerful approach that would reduce the
      recourse to Southern blotting in females with mental retardation of unknown
      etiology.

PMID- 12215256
TI  - Chromosome 7.

PMID- 12215257
TI  - Gene expression profiling of osteoclast differentiation by combined suppression
      subtractive hybridization (SSH) and cDNA microarray analysis.
AB  - Bone homeostasis is maintained by the balanced action of bone-forming osteoblasts
      and bone-resorbing osteoclasts. Multinucleated, mature osteoclasts develop from
      hematopoietic stem cells via the monocyte-macrophage lineage, which also give
      rise to macrophages and dendritic cells. Despite their distinct physiologic roles
      in bone and the immune system, these cell types share many molecular and
      biochemical features. To provide insights into how osteoclasts differentiate and
      function to control bone metabolism, we employed a systematic approach to profile
      patterns of osteoclast-specific gene expression by combining suppression
      subtractive hybridization (SSH) and cDNA microarray analysis. Here we examined
      how gene expression profiles of mature osteoclast differ from macrophage or
      dendritic cells, how gene expression profiles change during osteoclast
      differentiation, and how Mitf, a transcription factor critical for osteoclast
      maturation, affects the gene expression profile. This approach revealed a set of
      genes coordinately regulated for osteoclast function, some of which have
      previously been implicated in several bone diseases in humans.

PMID- 12215258
TI  - Transcriptional activation of C/EBPbeta gene by c-Jun and ATF2.
AB  - C/EBPbeta is one of the key transcription factors responsible for the induction
      of a wide array of genes. Like many proto-oncogenes and transcription factors,
      transcription of C/EBPbeta gene can be induced by multiple extracellular signals.
      Using nuclear extracts from lipopolysaccharide (LPS)-stimulated mouse liver, five
      trans-acting factor-binding motifs, URE1 (-376 to -352), URE2 (-253 to -223),
      URE3 (-220 to -190), URE4 (-123 to -103), and URE5 (-72 to -45) were identified
      by DNAse I footprinting assays. Competition and supershift analysis of the
      complexes formed at the URE2 and URE4 indicated that they contain CREB/ATF and AP
      1 family factors. Furthermore, recombinant ATF2 and c-Jun proteins from mammalian
      and bacterial cells can bind to URE2 and URE4 but not URE1. Cotransfection
      experiments showed that ATF2 and c-Jun activate the C/EBPbeta gene expression
      cooperatively through URE2 and URE4, and this activation was greatly increased
      under the treatment of low concentration of anisomycin. During acute phase
      response, the phosphorylation of c-Jun and ATF2 was found to correlate with
      C/EBPbeta gene expression. Taken together, our results provide the evidences that
      both c-Jun and ATF2 are the regulators of C/EBPbeta gene.

PMID- 12215260
TI  - An oxysterol-binding protein family identified in the mouse.
AB  - Oxysterols are oxygenated derivatives of cholesterol. They have been shown to
      influence a variety of biological functions including sterol metabolism, lipid
      trafficking, and apoptosis. Recently, 12 human OSBP-related genes have been
      identified. In this study, we have identified a family of 12 oxysterol-binding
      protein (OSBP)-related proteins (ORPs) in the mouse. A high level of amino acid
      identity (88-97%) was determined between mouse and human ORPs, indicating a very
      high degree of evolutionary conservation. All proteins identified contained the
      conserved OSBP amino acid sequence signature motif "EQVSHHPP," and most contained
      a pleckstrin homology (PH) domain. Using RT-PCR, each mouse ORP gene was found to
      exhibit a unique tissue distribution with many showing high expression in
      testicular, brain, and heart tissues. Interestingly, the tissue distribution of
      ORP-4 and ORP-10 were the most selective within the family. Expression of the
      various ORP genes was also investigated, specifically in highly purified
      populations of hemopoietic precursor cells defined by the lin(-) c-kit(+) Sca
      1(+) (LKS(+)) and lin(-) c-kit(+) Sca-1(-) (LKS(-)) immunophenotype. Most ORP
      genes were expressed in both LKS(+) and LKS(-) populations, although ORP-4
      appeared to be more highly expressed in the primitive, stem-cell enriched LKS(+)
      population, whereas ORP-10 was more highly expressed by maturing LKS(-) cells.
      The identification of a family of ORP proteins in the mouse, the frequently
      preferred animal model for in vivo studies, should further our understanding of
      the function of these proteins and their interactions with each other.

PMID- 12215261
TI  - Enhancement of antibody responses to an HIV-2 DNA envelope vaccine using an
      expression vector containing a constitutive transport element.
AB  - Because immune responses to DNA vaccines in humans remains suboptimal, strategies
      need to be devised to facilitate expression of the vaccine in vivo. One method to
      improve response to a DNA vaccine is to construct plasmid vectors with leader
      sequences and post-transcriptional elements that facilitate export of transcribed
      RNA. In this study, we sought to determine if a mammalian expression vector (pND
      14) containing a tissue plasminogen activator (TPA) leader sequence and a
      constitutive transport element (CTE) from simian retrovirus was superior to other
      mammalian expression vectors containing a post-transcriptional regulatory element
      (PRE) from hepatitis B virus (pCMV-link) or a minimal mammalian expression vector
      (pVAX1). Toward this objective, we evaluated protein expression of the HIV-2
      envelope gene (gp140) in vitro and immune responses in immunized mice. We found
      that pVAX1 produced three- to fourfold lower levels of gp140 in vitro (5 ng/ml)
      in contrast to the pCMV-link and pND-14 vectors. When we immunized groups of mice
      intradermally with two of the HIV-2 gp140 DNA vaccine constructs, we found that
      pND-14 induced higher levels of envelope-specific systemic and mucosal antibodies
      than pCMV-link. We conclude that expression vectors for DNA vaccines should
      contain TPA and CTE sequences to facilitate immune responses.

PMID- 12215259
TI  - The mouse alpha-fetoprotein promoter is repressed in HepG2 hepatoma cells by
      hepatocyte nuclear factor-3 (FOXA).
AB  - The mouse alpha-fetoprotein gene is expressed at high levels in the fetal liver
      and is transcriptionally silenced at birth. The repression is governed, at least
      in part, by the 250 base pair (bp) AFP promoter. We show here that the AFP
      promoter is dramatically repressed by HNF3 in HepG2 hepatoma cells. This
      repression is governed by the region between -205 and -150. Furthermore, this
      fragment can confer HNF3-mediated repression on a heterologous promoter. The
      repression is abolished by a mutation that is centered at -165. EMSA analyses
      using in vivo and in vitro synthesized proteins indicate that HNF3 proteins do
      not bind DNA from the -205 to -150 region. We propose that HNF3 represses AFP
      promoter activity through indirect mechanisms that modulate the binding or
      activity of a liver-enriched factor that interacts with the -165 region of the
      AFP promoter.

PMID- 12215262
TI  - Characterization of the rRNA genes of Ehrlichia chaffeensis and Anaplasma
      phagocytophila.
AB  - The rRNA genes of Ehrlichia chaffeensis and Anaplasma phagocytophila have been
      analyzed. The 16S rRNA genes were previously characterized for both of these
      agents. Southern hybridization was used to show that there are single copies of
      both the 16S and 23S rRNA genes in the genomes of each organism, and that the 16S
      rRNA genes were upstream from the 23S rRNA genes by at least 16 and 11 Kb for E.
      chaffeensis and A. phagocytophila, respectively. PCR amplification and gene
      walking was used to sequence the 23S and 5S rRNA genes, and show that these genes
      are contiguous and are likely expressed as a single operon. The level of homology
      between the E. chaffeensis and A. phagocytophila 23S and 5S rRNA genes, and 23S
      5S spacers, was 91.8, 81.5, and 40%, respectively. To confirm the hybridization
      data, genome walking was used to sequence downstream of the 16S rRNA genes, and
      although no tRNA genes were identified, open reading frames encoding homologues
      of the Escherichia coli succinate dehydrogenase, subunit C, were found in both E.
      chaffeensis and A. phagocytophila. Phylogenetic analysis using the 23S rRNA gene
      suggests that reorganization of the phylum Proteobacteria by division of the
      class Alphaproteobacteria into two separate subclasses, may be appropriate.

PMID- 12215263
TI  - Intranasal gene transfer by chitosan-DNA nanospheres protects BALB/c mice against
      acute respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) infection is often associated in infancy with
      life-threatening bronchiolitis, which is also a major risk factor for the
      development of asthma. At present, no effective prophylaxis is available against
      RSV infection. Herein, we describe an effective prophylactic intranasal gene
      transfer strategy utilizing chitosan-DNA nanospheres (IGT), containing a cocktail
      of plasmid DNAs encoding all RSV antigens, except L. A single administration of
      IGT (25 microg/mouse) induces expression of the mRNA and proteins of all antigens
      in the lung and results in a significant reduction of viral titers and viral
      antigen load after acute RSV infection of these mice. IGT-administered mice show
      no significant change in airway reactivity to methacholine and no apparent
      pulmonary inflammation. Furthermore, IGT results in significant induction of RSV
      specific IgG antibodies, nasal IgA antibodies, cytotoxic T lymphocytes, and
      interferon-gamma production in the lung and splenocytes compared with controls.
      Together, these results demonstrate the potential of IGT against acute RSV
      infection.

PMID- 12215264
TI  - Genetic modification of adenovirus 5 tropism by a novel class of ligands based on
      a three-helix bundle scaffold derived from staphylococcal protein A.
AB  - The use of adenovirus (Ad) as an efficient and versatile vector for in vivo tumor
      therapy requires the modulation of its cellular tropism. We previously developed
      a method to genetically alter the tropism of Ad5 fibers by replacing the fiber
      knob domain by an extrinsic trimerization motif and a new cellular ligand.
      However, fibers carrying complex ligands such as single-chain antibody fragments
      did not assemble into functional pentons in vitro in the presence of penton base,
      and failed to be rescued into infectious virions because of their inability to
      fold correctly within the cytoplasm of Ad-infected cells. Here we show that the
      coding sequence for a disulfide bond-independent three-helix bundle scaffold Z,
      derived from domain B of Staphylococcal protein A and capable of binding to the
      Fc portion of immunoglobulin (Ig) G1, could be incorporated into modified
      knobless Ad fiber gene constructs with seven shaft repeats. These fiber gene
      constructs could be rescued into viable virions that were demonstrated to enter
      293 cells engineered for IgG Fc surface expression but not unmodified 293 cells,
      via a mechanism that could be specifically blocked with soluble Fc target
      protein. However, the tropism modified viruses showed a slightly impaired
      cellular entry and a lower infectivity than wildtype (WT) virus. In addition, we
      generated recombinant fibers containing an IgA binding Affibody ligand, derived
      from combinatorial specificity-engineering of the Z domain scaffold. Such fiber
      constructs also showed the expected target specific binding, indicating that the
      affibody protein class is ideally suited for genetic engineering of Ad tropism.

PMID- 12215265
TI  - Prolonged islet allograft survival by adenovirus-mediated transfer of sICAM-1/Ig
      immunoadhesin gene.
AB  - Administration of monoclonal antibodies directed against the leukocyte function
      associated antigen 1 (LFA-1)-intercellular adhesion molecule 1 (ICAM-1) pathway
      showed that these costimulatory molecules play a key role in allograft rejection.
      Here, adenoviral gene transfer of an immunoadhesin, sICAM-1/Ig, was used to
      prolong islet allograft survival in a mouse model, and was compared with anti-LFA
      1 antibody administration. A replication-deficient recombinant adenoviral vector
      encoding a chimeric protein, in which the extracellular domain of ICAM-1 is
      covalently linked to the C(H)2-C(H)3 domains of an IgG1, was used for gene
      transfer. C3H murine islets were transplanted under the kidney capsule of
      streptozotocin-induced diabetic BALB/c mice. Experimental groups underwent
      adenovirus vector administration either in vivo (intravenous injection) or ex
      vivo (gene transfer to the graft), and control groups received either an empty
      vector (Ad.null) or an anti-LFA-1 monoclonal antibody. Graft survival was
      significantly prolonged by in vivo sICAM-1/Ig gene transfer as compared with both
      Ad.null and anti-LFA-1 groups, but not by ex vivo gene transfer. Histological
      examination of the grafts showed the presence of a mononuclear infiltrate within
      functioning grafts, suggesting that the homing of alloreactive T cells was not
      altered. In vitro T cell proliferation experiments indicated that sICAM-1/Ig
      exerted agonist effects on both CD4(+) and CD8(+) T cells.

PMID- 12215266
TI  - Adeno-associated virus vector-mediated minidystrophin gene therapy improves
      dystrophic muscle contractile function in mdx mice.
AB  - Duchenne muscular dystrophy (DMD) is the most common disabling and lethal genetic
      muscle disorder, afflicting 1 of every 3500 males. Patients with DMD experience
      progressive muscle degeneration and weakness and succumb to respiratory or
      cardiac failure by their early twenties. No treatment is currently available for
      DMD. Mutations in the dystrophin gene result in lack of a functional dystrophin
      protein in striated muscle, which induces instability in the muscle cell membrane
      leading to persistent muscle injury after contraction. We have previously created
      novel minidystrophin genes and demonstrated that adeno-associated virus (AAV)
      mediated intramuscular delivery of the minigenes effectively ameliorated mdx
      dystrophic histopathology and led to normal cell membrane integrity for more than
      1 year. In this paper, we investigated whether AAV-minidystrophin could also
      improve mdx muscle contractile function. Two-month-old adult male mdx mice, with
      established muscular dystrophy, were given a single-dose injection of an AAV
      minidystrophin vector in the tibialis anterior (TA) muscle of one leg, with the
      untreated contralateral leg used as a control. The treated TA muscle showed both
      (1) a significant increase in isometric force generation and (2) a significant
      increase in resistance to lengthening activation-induced muscle force decrements.
      We conclude that AAV-minidystrophin gene treatment is effective in improving mdx
      muscle contractile function.

PMID- 12215267
TI  - Stimulation of angiogenesis by Cyr61 gene: a new therapeutic candidate.
AB  - Cyr61 is a secreted, cysteine-rich heparin-binding protein that is associated
      with extracellular matrix and cell surface, and has been demonstrated to be
      proangiogenic in vitro. In the present study we evaluated the angiogenic effect
      of human Cyr61 in an adenoviral context in the rabbit ischemic hindlimb model.
      For this purpose, three randomized groups of New Zealand White rabbits received
      intramuscular injections of 5 x 10(8) infectious units of an adenovirus carrying
      either the Cyr61 gene (Ad-Cyr61), the vascular endothelial growth factor gene (Ad
      VEGF(165)) used as the angiogenic gene of reference, or no transgene (Ad-Null),
      10 days after femoral artery excision in one limb. Perfusion of the ischemic limb
      was evaluated before adenoviral treatment (day 10) and 30 days postinjection (day
      40). Angiographic, hemodynamic, and histologic parameters indicated that animals
      in the Ad-Cyr61 group had significantly better perfusion than in the Ad-Null
      group. Interestingly, this improvement exceeded that achieved with Ad-VEGF(165).
      In conclusion, Cyr61 gene transfer appears potent in stimulating limb
      revascularization, thereby promoting great improvement in tissue perfusion in the
      ischemic limb. These findings indicate that Cyr61 could be a promising
      therapeutic candidate for treating severe peripheral ischemic diseases.

PMID- 12215268
TI  - Gene transfer to the pleural mesothelium as a strategy to deliver proteins to the
      lung parenchyma.
AB  - The pleura covers the lung parenchyma, chest wall, and diaphragm with a single
      layer of flat cells that are easy to genetically modify with adenovirus (Ad)
      vectors. Although intrapleural gene therapy has been used to treat intrapleural
      disorders, we hypothesized that it may also be used to deliver extracellular gene
      products to the lung parenchyma. In this context, this study is based on the
      concept that administration of adenovirus gene transfer vectors into the pleural
      cavity will mediate expression of gene products in mesothelial cells, and that
      the extracellular products produced by these genetically modified cells will
      reach the lung parenchyma. To assess this concept, Ad(beta)gal (expressing beta
      galactosidase [beta-Gal]) or AdLuc (expressing luciferase) was administered into
      the right pleural cavity of BALB/c mice, as compared with intravenous injection
      via the jugular vein or the intratracheal route. Histologic assessment of lungs
      and pleural surface after intrapleural administration of Ad(beta)gal demonstrated
      beta-Gal expression limited to the pleural mesothelium and cells adjacent to the
      pleural surface. Right intrapleural administration of AdLuc showed higher level
      of luciferase in both the right and left lung (right vs. left, p > 0.8), compared
      with the intratracheal (p < 0.05) or intravenous routes (p < 0.02), that is,
      unilateral intrapleural administration is sufficient to transfer genes
      bilaterally to the pleura. To assess the ability of intrapleural gene transfer to
      modify lung parenchymal processes, CT26.CL25 tumor cells (3 x 10(5)) were
      injected via the jugular vein to generate tumor metastases in the lung parenchyma
      followed 24 hr later by administration to the right pleura of 5 x 10(8) PFU of
      Adsflt (an Ad "antiangiogenesis" vector expressing a soluble, secreted,
      extracellular portion of the Flt-1 receptor for vascular endothelial growth
      factor). Compared with phosphate-buffered saline, or the control vector AdNull
      (no transgene), mice receiving Adsflt by the intrapleural route had a marked
      suppression of tumor growth in the parenchyma of both lungs as assessed 12 days
      after tumor administration (p < 0.005). Treatment of preestablished lung
      metastases with Adsflt administered by the intrapleural route significantly
      improved long-term survival as compared with control animals (p < 0.0001). Thus,
      although intrapleural administration of an Ad vector encoding an intracellular
      protein mediates gene expression only in mesothelial cells and the local tissues,
      intrapleural delivery of a vector expressing a secreted protein can be used to
      modify processes throughout the lung parenchyma. In the context that
      intravascular gene transfer is an ineffective strategy to deliver gene products
      to the lung parenchyma, and that intratracheal administration is associated with
      alveolar inflammation secondary to host defenses against Ad vectors, these
      findings demonstrate that intrapleural administration represents a strategy that
      can be used to effectively deliver extracellular gene products to the lung
      parenchyma via a site that is readily accessible, and where inflammation against
      the vector will not have significant pathophysiologic consequences.

PMID- 12215269
TI  - High in vivo production of a model monoclonal antibody on adenoviral gene
      transfer.
AB  - The therapeutic potential of monoclonal antibodies (MAbs) for treating a variety
      of severe or life-threatening diseases is high. Although intravenous infusion
      appears to be the simplest and most obvious mode of administration, it is not
      applicable in many long-term treatments. It might, however, be advantageously
      replaced by gene/cell therapies, rendering treatments cost-effective and
      eliminating the short- and long-term side effects associated with injection of
      massive doses of antibodies. Grafting of ex vivo genetically modified cells of
      various types has already been used for in vivo production and systemic delivery
      of MAbs in mice. However, although sustained for long periods of time, serum
      levels of ectopic MAbs were low. We show here that in vivo administration to mice
      of a first-generation adenoviral vector expressing a model MAb also permits
      achievement of the same goal, but with 100 to 200 times better efficiency that in
      any other case of gene transfer described thus far. We also investigated for
      possible anti-idiotypic response against the ectopic MAb. None was detected in
      the animals expressing the lowest levels of ectopic MAb production; a response
      was detected among the highest producers. In the latter case, however, the
      response was low and could not exert any significant neutralizing activity. In
      conclusion, our work indicates that high levels of circulating ectopic MAb can be
      obtained on direct in vivo gene transfer without inducing an anti-idiotypic
      response sufficiently robust to exert a neutralizing effect. This observation is
      encouraging in the perspective of clinical applications of this technology.

PMID- 12215270
TI  - Upregulation of Bag-1 by ex vivo gene transfer protects rat livers from
      ischemia/reperfusion injury.
AB  - Bag-1 exerts powerful antiapoptotic effects by binding and stabilizing Bcl-2 and
      interacting with the tumor necrosis factor receptor type I-induced death signal.
      We examined the effects of overexpression of Bag-1 by ex vivo adenoviral gene
      transfer on cold (4 degrees C for 24 hr) ischemia/reperfusion (I/R) injury of rat
      livers. Treatment with adenoviral Bag-1 (Ad-Bag-1) significantly improved portal
      venous blood flow, increased bile production, and improved hepatic function in
      the ex vivo model of cold ischemia followed by isolated perfusion. Moreover, the
      survival of orthotopic liver grafts subjected to cold ischemia increased from 50%
      in Ad-betaGal-treated controls to 100% after Ad-Bag-1 therapy. This effect
      correlated with preserved hepatic architecture, improved liver function, and
      depressed infiltration by neutrophils. Furthermore, the activation of
      infiltrating T cells, as measured by CD25, IL-2, and IFN-gamma mRNA expression
      was markedly reduced in the Ad-Bag-1 group. Hence, gene therapy-induced Bag-1
      overexpression prevented cold I/R injury in rat livers. These findings provide
      the rationale for refined novel treatment of donor livers and may ultimately
      improve the overall success of liver transplantation.

PMID- 12215271
TI  - Serum and ascites neutralizing antibodies in ovarian cancer patients treated with
      intraperitoneal adenoviral gene therapy.

PMID- 12215272
TI  - Clinical protocol. Tumor site specific phase I evaluation of safety and efficacy
      of hepatic arterial infusion of a matrix-targeted retroviral vector bearing a
      dominant negative cyclin G1 construct as intervention for colorectal carcinoma
      metastatic to liver.

PMID- 12215274
TI  - Clinical characteristics of acute ischemic syndrome in China.
AB  - OBJECTIVE: To analyse the characteristics and therapies of patients with acute
      ischemic syndrome in China. METHODS: This study is part of the international
      multicentre registry for acute ischemic syndrome. Since April 1999, the data of
      patients admitted to designated hospitals with acute ischemic cardiac chest pain
      were collected by filling in Case Report Forms offered by the Canadian
      Cardiovascular Collaboration. The main clinica l characteristics and in  hospital
      events of the patients were recorded. RESULTS: Fifteen hundred and nine cases of
      acute ischemic syndrome from 34 hospitals nationwide were enrolled in the
      registry (including unstable angina and non Q-wave myocardial infarction). The
      mean age of the patients was 62.3. Male dominance (62.2%) was noted. The
      percentages of patients with chest pain at presentation and abnormal ECG were
      47.8% and 89.5%, respectively. The most common clinical diagnosis on admission
      was unstable angina, accounting for 91.3% of the patients and non Q-wave
      myocardial infarction (MI), accounting for the other 8.7%. During
      hospitalization, the following interventions were given: thrombolytic therapy in
      50 cases (3.3%), coronary angiography in 528 cases (35.0%), percutaneous
      transluminal coronary angioplasty (PTCA) in 253 cases (16.8%) and coronary artery
      bypass graft surgery (CABG) in 62 cases (4.1%). Nitrate (oral or patch ) and anti
      platelet therapy were used in 1460 cases (96.8%) and 1441 cases (95.5%),
      respectively. The incidence of in  hospital major events was 18.8%, in cluding 18
      deaths (1.2%), with the most common causes being severe arrhythmias and sudden
      death. CONCLUSIONS: Patients with acute ischemic syndrome in China have mostly
      been diagnosed as cases of unstable angina. A relatively high PTCA rate but low
      CABG rate was noted in China. The most common cause of in  hospital death is
      severe arrhythmias or sudden death.

PMID- 12215275
TI  - Autoantibodies against the myocardial beta1-adrenergic and M2-muscarinic
      receptors in patients with congestive heart failure.
AB  - OBJECTIVE: To determine whether autoantibodies against beta(1)-adrenergic and
      M(2)-muscarinic receptors are related to patients with congestive heart failure
      (CHF). METHODS: Both synthetic peptides corresponding to amino acids sequence 197
      222 and 169-173 of the second extracellular loops of the beta(1) and M(2)
      receptors were used as antigens to screen sera from 265 patients.188 were
      congestive heart failure ( CHF) patients with different heart diseases, among
      them 42 were ischemic cardiomyopathy (ICD) and 52 were idiopathic dilated
      cardiomyopathy (IDCM)  44 were hypertensive heart disease (HHD)  50 were
      rheumatic valvular heart disease (RVHD); 77 were controls, among them 36 were
      simple hypertension and 41 were healthy donors (NC). RESULTS: Positive sera for
      beta(1)-adrenergic receptor was found in 45.73% (86/188) of CHF patients, while
      in the controls it was 10.4% (8/77) (P < 0.01); positive sera for M(2)-muscarinic
      receptor in CHF patients was found in 49.5% (99/188), while in the control it was
      11.7% (9/77) (P < 0.01). The positive ratio of autoantibodies against beta(1)
      adrenergic and M(2)-muscarinic receptors in CHF patients with cardiac function
      class II-III (NYHA) were significantly higher than cardiac function class IV. The
      average titer of autoantibodies against beta(1)-adrenergic and M(2)-muscarinic
      receptors of the former was significantly higher than the latter; 56.1% of
      patients with autoantibodies against beta(1)-adrenergic receptor had
      autoantibodies against M(2)-muscarinic receptor. CONCLUSIONS: Autoantibodies
      against beta(1)-adrenergic receptor and M(2)-muscarinic receptor were found in
      sera from heart failure patients with different cardiac diseases. We propose that
      autoantibodies against beta(1) and M(2) receptors are not only related to the
      IDCM, but also to cardiac structural and functional changes.

PMID- 12215276
TI  - Dextran uterine artery embolization to treat fibroids.
AB  - OBJECTIVES: To analyze the technical aspects of uterine artery embolization with
      dextran microspheres and to evaluate the effectiveness of this technique as the
      primary treatment of uterine fibroids in a series of 38 patients. METHODS: Thirty
      eight volunteers (age range, 24-48 years; mean, 37.2 years) with symptoms caused
      by uterine fibroids (menorrhagia, mass-related symptoms, and pelvic pain) were
      randomly included in this study. The fibroids were single in 32 patients and
      multiple in 6 patients. According to the tumor location, subserous fibroids were
      found in 4 patients and interstitial or submucosal fibroids in 34. Tumor size was
      from 2 to 10.9 cm in diameter. We performed embolization with a single Headhunter
      catheter using the right-femoral artery approach, injection of dextran
      microspheres (225-450 micro m), and an absorbable gelatin sponge. Follow-up
      included clinical and sonographic examinations at one-month intervals for 6
      months. RESULTS: Embolization was successfully performed in all patients. Post
      procedural pain control was good in 35 (92%) patients. In most patients, symptoms
      were improved at 3 months (36/38, 95%). Clinical failure of the treatment
      occurred in only 2 patients (2/38, 5%). Progressive reduction in leiomyoma size
      was revealed during sonographic follow-up, and the reduction rate at the sixth
      month after embolization was 68%. The tumor had vanished in five submucosal
      fibroid patients. Histopathological tests showed that the tumor was degenerative
      as fibrosis and hyalinosis. CONCLUSIONS: Uterine artery embolization with dextran
      microspheres is a micro-invasive method for the treatment of uterine fibroids. It
      is clinically effective in most patients and induces a progressive reduction in
      the size of fibroids. Based on this study, we believe that this new technique is
      much more suitable for submucosal fibroids with massive menorrhagia.

PMID- 12215277
TI  - Sentinel lymph nodes lymphoscintigraphy and biopsy in breast cancer.
AB  - OBJECTIVES: To determine the clinical value of sentinel lymph node (SLN)
      detection by lympho- scintigraphy and gamma ray detecting probe (GDP) and to
      assess the value of hematoxylin and eosin (H&E) staining combined with
      immunohistochemistry (IHC) analys is for detecting micrometastasis in lymph nodes
      (LNs). METHODS: Forty-two patients with breast cancer were included in this
      study. (99)Tc(m)-dextran was injected peritumourally. Lymphoscintigraphy images
      were obtained in anterior and lateral views. SLNs were removed with the aid of
      GDP during surgery. A standard axillary lymph nodes (ALNs) dissection was
      performed. All lymph nodes were first analyzed by HE staining. When all of the
      SLNs in a patient were negative, the ALNs were subjected to additional HE
      staining combined with IHC analysis. RESULTS: SLNs were successfully detected and
      removed in 39 (92.9%) of the 42 patients. The sensitivity, specificity and
      accuracy of SLN biopsy were 92.9% (13 in 14), 100% (25 in 25) and 97.4% (38 in
      39) respectively.   Additional HE staining combined with IHC analysis of the ALNs
      detected micrometastasis in 3 SLNs (2 cases), but there were no positives in the
      non-sentinal lymph nodes (NSLNs). CONCLUSIONS: This study suggests that
      lymphoscintigraphy and GDP may be used to detect SLN. Additional HE staining
      combined with IHC analysis of the ALNs may help predict micrometastasis. Biopsy
      of SLN may be an accurate method for staging breast cancer.

PMID- 12215278
TI  - Evaluation of photodynamic therapy of skin cancers with partial differential
      alpha-aminolevulinic acid.
AB  - OBJECTIVE: To use partial differential -aminolevulinic acid induced photodynamic
      therapy (ALA-PDT) increasingly in treating skin cancers and other diseases in
      many countries and to explore the efficacy of ALA-PDT for skin cancers in China.
      METHODS: Eighty-eight patients, including 34 cases of basal cell carcinoma (BCC),
      32 cases of squamous cell carcinoma (SCC), two cases of basal-squamous cell
      carcinoma (BSCC), one case of verrucuous carcinoma, nine cases of Bowen disease,
      two cases Paget disease of the nipple and eight cases of extramammary Paget
      disease, were treated by the partial differential alpha-aminolevulinic acid
      induced photodynamic therapy first in China from 1997 to 2000. RESULTS: All BCC,
      including 11 cases of superficial lesions and 29 solid lesions, achieved complete
      reaction (CR) by 1-4 times of the ALA-PDT. Except one patient with adenoid SCC
      (grade III), all SCC (grade I and grade II) patients achieved complete remission
      by 3-6 times of ALA-PDT. All Bowen diseases achieved complete reaction by 1-4
      times. Although for Paget diseases it could not cure the disease simply by ALA
      PDT, it could control the symptoms. The recurrence rates were 11% (4/34) for BCC,
      and 22% (7/32) for SCC by following up 1-3 years after the therapy. The
      continuous therapy is still effective. CONCLUSIONS: ALA-PDT is an effective, non
      traumatic treatment for patients with BCC, SCC, Bowen and Paget diseases. It is
      especially suitable for older and weaker patients or those who are not tolerable
      to other therapies. It also has a unique advantage for tumors in specific
      anatomical areas. It is a new alternative modality for skin cancer therapies.

PMID- 12215279
TI  - Three-dimensional CT angiography and surgical correlation in the evaluation of
      intracranial aneurysms.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of three-dimensional CT
      angiography in the surgical treatment of intracranial aneurysms. METHODS: Twenty
      four patients suspected of intracranial aneurysms underwent routine catheter four
      vessel angiography, three dimensional CT angiography (3D-CTA), magnetic resonance
      angiography (MRA) or conventional digital subtraction angiography (DSA). RESULTS:
      A total of 28 aneurysms were detected by CT angiography in this study. Twenty-one
      patients each had a single aneurysm, two patients each had two aneurysms, and one
      had three aneurysms. The shapes of aneurysms revealed by 3D-CTA were round in 20
      lesions, elliptical in 5, and 1 obulated in 3. Of the 24 lesions which were
      completely disclosed during surgery, the shapes correlated well with the 3D-CT
      angiograms. The mean diameter of the aneurysmal neck was 5.9 mm in 3D-CTA images,
      with the smallest being 1.6 mm and the largest 13.7 mm. The size was very close
      to the actual size measured at surgery (P < 0.001), revealing that 3D-CT
      angiograms correlated well with surgical findings. Compared with images obtained
      by routine catheter four-vessel angiography, MRA and DSA, 3D-CTA images depicted
      the relationship of aneurysms to parent vessels and other branches more clearly.
      CONCLUSION: 3D-CTA enables surgeons to understand the 3D structure of
      intracranial aneurysms and is very useful in planning the surgical treatment of
      cerebral aneurysms.

PMID- 12215280
TI  - Microsurgical treatment of Nelson's syndrome.
AB  - OBJECTIVE: To discuss the etiology, diagnostic criteria and treatment of Nelson's
      syndrome. METHODS: Twenty-three patients with Nelson's syndrome who were treated
      in our department over the last 19 years were analyzed retrospectively. Removal
      of adenoma by the transsphenoidal approach was done in 21 patients and by
      transfrontal craniotomy in 2. The follow-up period ranged from six months to nine
      years. RESULTS: The incidence of Nelson's syndrome was 7.7% in a series of 300
      patients with Cushing's  disease treated by microsurgery in the same period.
      Hyperpigmentation was relieved and adrenocorticotropic hormone (ACTH) levels
      decreased in all patients after tumor excision. Eight patients with visual
      disturbance improved after surgery. The curative and remission rates were 56.5%
      and 26.1%, respectively. CONCLUSIONS: Transsphenoidal microsurgical removal of
      pituitary ACTH adenoma is the first choice in the prevention and treatment of
      Nelson's syndrome. Regular follow-up examinations should be performed over a long
      time.

PMID- 12215281
TI  - Clinical pathological study of treatment of chronic hepatitis with hyperbaric
      oxygenation.
AB  - OBJECTIVE: To detect the feasibility and theoretic basis for treatment with
      hyperbaric oxygenation (HBO) in chronic hepatitis and to compare the changes in
      hepatic function, immunity, pathologic morphology, ultrastructure and HBV in
      hepatic tissues before and after treatment. METHODS: Sixty cases of chronic
      hepatitis were randomly selected and divided into two groups: the experiment (n =
      30) and control groups (n = 30). Patients in the experimental group were treated
      with HBO for 6 courses. Patients in the control group were treated for 60 days
      with the usual drugs used in the clinic. The function and bloodstream graph of
      liver were examined and liver biopsies were made before and after treatments.
      Routine paraffin sections were stained with HE and observed under the light
      microscope. Ultra thin slides from paraformaldehyde and glutaraldehyde fixed
      liver tissue were stained with lead citrate and observed with the transmission
      electric microscope. HBsAg and HBcAg in liver of the experimental group were
      detected with ABC immunohistochemistry method before and after treatment.
      RESULTS: For the experimental group, ALT, SB, gamma-GT, AKP, IgG, and IgM in
      blood and the degeneration and necrosis of hepatocytes were remarkably decreased
      (P < 0.05 ), the mean contractive wave of bloodstream in liver and the
      bloodstream in right ramus of janitrix were remarkably increased (P < 0.05), and
      the swelling of mitochondria, increase of lysosomes, generation of Kupffer cells,
      infiltration of lymphocytes in portal area and capillary generation were all
      remarkably all eviated (P < 0.05) after treatment with HBO. There were
      significant differences between the experimental and control groups after
      treatment with different methods (P < 0.05). For patients in the experimental
      group, the fibrosis and fat-storing cells in the liver were not reduced (P >
      0.05), and the expression of HBsAg and HBcAg in liver was not weakened (P < 0.05)
      after treatment. CONCLUSIONS: Treatment with HBO for chronic hepatitis was
      effective and recommendable, but it could not reverse liver fibrosis. However, it
      might be able to delay or prevent the liver from fibrosis, so it might be more
      effective at the early and middle stages of chronic hepatitis. HBO could not
      inhibit the HB virus. So we consider that treatment with HBO should be
      simultaneous with anti HBV therapy.

PMID- 12215282
TI  - Klebsiella pneumoniae: epidemiology and analysis of risk factors for infections
      caused by resistant strains.
AB  - OBJECTIVE: To analyze the epidemiology of hospital and community-acquired
      infections caused by  Klebsiella pneumoniae (K. pneumoniae) and risk factors for
      infections caused by resistant strains. METHODS: A retrospective observational
      study was performed to analyze the relationship between antimicrobial use and
      bacterial resistance. RESULTS: A K. pneumoniae infection was diagnosed in 0.47%
      of patients (169 of 36 179) admitted to the hospital between 1 March 1999 and 31
      August 2000. Of the 169 isolates, 166 (98.2%) were resistant to at least one
      antimicrobial and 91.1% (154/169) to two or more antibiotics. 98% were resistant
      to ampicillin, 77% to piperacillin, 64% to cephalothin, 60% to
      ampicillin/sulbactam, 59% to cefoperazone, 57% to cefazolin, 55% to cefuroxime,
      51% to TMP-SMZ, 51% to tobramycin, 50% to gentamicin, 49% to aztreonam,
      cefetaxime and ceftriaxone respectively, 47% to ceftazidime, 47% to cefepime, 46%
      to ciprofloxacin, 46% to ticarcillin/clavulanate, 44% to amikacin, 38% to
      cefoxitin, 22% to piperacillin/tazobactam, while all strains were tested
      susceptible to imipenem. CONCLUSIONS: Prior receipt of amtimicrobial therapy was
      significantly associated with infection caused by a resistant organism and most
      strains were resistant to multiple antibiotics.

PMID- 12215283
TI  - An experimental study of colonic mucosal graft for urethral reconstruction.
AB  - OBJECTIVE: To investigate the possibility of urethral reconstruction with a free
      colonic mucosal graft. METHODS: Ten female dogs underwent a procedure in which
      the urethral mucosa was totally removed and replaced with a free graft of colic
      mucosa. A urodynamic study was performed before the operation and sacrifice. The
      dogs were sacrificed 8 to 16 weeks after the operation for histological
      examination of the urethra. RESULTS: Urethral stricture developed in 1 dog. The
      results of urody namic studies showed that the difference in maximum urethral
      pressure between pre-operation and pre-sacrifice in the remaining 9 dogs was not
      of significance (P > 0.05). Histological examination revealed that the colonic
      free mucosa survived inside the urethral lumen of the 9 dogs. Plicae surface and
      unilaminar cylindric epithelium of the colonic mucosa was observed in dogs
      sacrificed 8 weeks after the operation. Plicae surface and unilaminar cylindric
      epithelium of the colonic mucosa was not observed and metaplastic transitional
      epithelium covered a large proportion of the urethral mucosa in dogs sacrificed
      12 weeks after the operation. CONCLUSIONS: Urethral mucosa can be replaced by
      colonic mucosa without damaging the continence mechanism in female dogs. This
      technique is useful when local or preputial skin and buccal or bladder mucosa are
      not available.

PMID- 12215284
TI  - Chronic treatment of enbrel in rats with isoproterenol-induced congestive heart
      failure limits left ventricular dysfunction and remodeling.
AB  - OBJECTIVE: To investigate the effect of chronic treatment of enbrel (EB), a TNF
      alpha antagonist, in a well defined congestive heart failure (CHF) rat model and
      test the hypothesis that chronic treatment of EB in CHF rats may limit the
      progression of Left ventricular (LV) dysfunction and structure remodeling and
      decrease cardiac IL-1beta levels. METHODS: We measured cardiac conformation,
      contractile performance and cytokines level in 8 age-matched normal adult rats
      (control group) and 8 rats with isoproterenol (ISO)-induced Heart failure (ISO
      group) and 8 rats with ISO-induced lesion but received EB treatment (EB group).
      RESULTS: LV end diastolic diameter and LV end systolic diameter in EB group were
      significantly less and LV fractional shortening was significantly larger than ISO
      group (9.2 +/- 0.3 mm vs 9.5 +/- 0.2 mm, 5.8 +/- 0.5 mm vs 6.5 +/- 0.3 mm, 0.37
      +/- 0.03 vs 0.31 +/- 0.02, P < 0.05, P < 0.01, P < 0.01 respectively , but there
      was no significant difference of LV posterior wall thickness at end diastole
      between the two groups; LV end systolic pressure (P(ES)) dp/dt(max) in EB group
      were significantly greater than ISO group (104.8 +/- 4.6 mm Hg vs 98.4 +/- 4.9 mm
      Hg, 8395 +/- 940 mm Hg/s vs 6898 +/- 612 mm Hg, P < 0.05 P < 0.01 respectively),
      and LV end diastolic pressure (P(ED)) dp/dt(min), time constant of LV relaxation
      were significantly lower than ISO group (3.8 +/- 0.6 mm Hg vs 7.1 +/- 0.8 mm Hg, 
      5963 +/- 475 mm Hg/s vs-5030 +/- 316 mm Hg/s,15.4 +/- 0.8 ms vs 21.3 +/- 1.4 ms,
      P < 0.01, respectively . Although cardiac contractile performance in the EB group
      was greatly improved, there still was a big gap when compared with the control
      group. The ratio of LV weight to body weight in the EB group was significantly
      higher than control group 2.82 +/- 0.07 mg/g vs 2.28 +/- 0.08 mg/g, P < 0.01 but
      there was no significant difference when compared with the ISO group. There was
      no significant difference between the serum level of TNF-alpha in EB group and
      ISO group the it could not be detected in control group. TNF-alpha levels in LV
      of EB group was significantly higher than control group, 757.6 +/- 46.8 pg/g vs
      367.5 +/- 22.7 pg/g, P < 0.01 but there was no significant difference when
      compared with ISO group. The IL-1beta level in LV of EB group was significantly
      lower than ISO group 356.2 +/- 28.5 pg/g vs 518.4 +/- 32.5 pg/g, P < 0.05 and it
      could not be detected in control group. The serum level of IL-1beta could not be
      detected in any rats. CONCLUSION: EB administered as soon as possible when ISO
      induced myocardial necrosis occurs can greatly improve cardiac contraction, and
      the improvement may be partly due to a decrease in the IL-1beta level in LV,
      besides the direct blocking effect of EB on TNF-alpha. EB can alleviate cardiac
      remodeling by its effect on LVEDD.

PMID- 12215285
TI  - Expression of recombinant adeno-associated virus in the brain of rats with a
      focal embolic stroke via carotid artery.
AB  - OBJECTIVE: To study whether recombinant adeno-associated virus (rAAV)  mediated
      foreign gene, LacZ, could pass the blood  brain barrier by intra-carotid artery
      delivery and express in vivo in ischemic brain of the focal embolic stroke rats
      to investigate a possibility of delivering foreign gene through carotid artery to
      treat acute ischemic stroke. METHODS: The carotid artery territory in 41 rats was
      embolized with or without arterial-like fibrin rich clots to make a model of
      focal embolic stroke rat. rAAV containing LacZ gene (rAAV-LacZ) was constructed
      in 293 cells by calcium phosphate cotransfection. The rats were assigned to one
      of the following treatments: 1 control (without embolism) groups, including PBS
      treated (n = 6), pLacZ treated (n = 6 ) and rAAV-LacZ treated (n = 6): 2 embolic
      groups, including embolism + PBS (n =7),embolism + pLacZ (n = 8) and embolism +
      rAAV-LacZ (n = 8). Brains were cryosectioned and kappa-Gal stain was performed at
      2, 4, and 8 weeks, respectively, after transfection, and then infarct volume was
      measured and the percentage of LacZ staining-positive cells was calculated.
      RESULTS: In all the control groups and embolism + PBS treated animal, no kappa
      Gal staining-positive cells were found, but in embolism + pLacZ (n = 8) and
      embolism+rAAV-LacZ groups a lot of kappa-Gal staining-positive cells were found.
      The expression cells were in the tissues around the infarction. The gene
      expression persisted only nearly four weeks in embolic group with pLacZ. In the
      embolic group with rAAV-LacZ the expression was very stable during the experiment
      course (eight weeks) and the percentage of the expressed cells was significantly
      higher than that of its contralateral areas at the same time points,
      respectively. CONCLUSIONS: The plasmid vector and rAAV could enter the brain
      through the ischemia-damaged blood barrier and foreign gene can be expressed in
      brain. The positive gene expression is mainly in the peripheral areas of the
      infarction. rAAV as a permanent expression vector may ultimately be used for gene
      therapy of human ischemia cerebravascular diseases.

PMID- 12215286
TI  - Cholinergic receptor activity after quinolinic acid caused cerebral injury    in
      rats.
AB  - OBJECTIVE: To provide a useful biological index for clinical diagnosis of
      Alzheimer's disease (AD) by determination the functional changes in the central
      cholinergic nerve and their effects on the peripheral lymphatic system. METHODS:
      The learning and memory impairment model was established through intraventricular
      injecting quinolinic acid (QA) repeatedly. RESULTS: There was a significant
      decline of cholineacetyltransferase (ChAT) in cerebral cortex and hippocampus
      after QA injection. The significantly lower binding activities of acetylcholine
      muscarinic (M) and nicotinic (N) cholinergic receptors in the hippocampus and
      cortex in the QA group were found as compared with the sham-operated group (P <
      0.01). Similar changes were found in the binding activities of M-and N-receptors
      on spleen lymphocytes. CONCLUSION: Certain lesion of the central nervous system
      can be reflected in peripheral spleen lymphocytes, which may be an important
      reference to diagnose the changes of the central nervous system.

PMID- 12215287
TI  - Rat model of erectile dysfunction caused by cavernous nerve ablation.
AB  - OBJECTIVE: To identify the rat cavernous nerve and establish a rat model of
      erectile dysfunction (ED) caused by injury of the cavernous nerve. METHODS:
      Twenty rats underwent dissections. Cavernous nerves were identified with the aid
      of an operating microscope and confirmed by electrical stimulation. Then, 42
      experimental rats were randomized into 3 groups, including sham-operated controls
      and unilateral and bilateral cavernous nerve ablation groups. Three weeks after
      surgery, rat models were evaluated with the Apomorphine test. RESULTS: The major
      pelvic ganglion lies on either side of the dorsolateral lobes of the prostate.It
      includes 2 inflows, one called hypogastric nerve and the other, the pelvic nerve.
      The largest outflow is termed the cavernous nerve. Stimulus parameters which
      could induce obvious penile erection were 5 volts, a frequency of 20 Hertz and a
      duration of 5 milliseconds. Three weeks after surgery, apomorphine could induce
      penile erection of each rat in the controls with a mean of 2.57 +/- 1.40
      erections in 30 minutes, while there were no erections (0.00 +/- 0.00) in either
      the unilateral or bilateral groups. CONCLUSIONS: The rat large ganglion and its
      cavernous nerve can be easily identified and it produces an obvious response to
      electrical stimulation. Rats are low cost animals to purchase, easy to house and
      very available making an ideal animal for developing an ED model caused by
      cavernous nerve injury. In addition, our study showed that in the early period of
      cavernous nerve ablation, unilateral and bilateral treated rats lost erectile
      capacity.

PMID- 12215288
TI  - Role of natural killer T cells in Graves' disease.
AB  - OBJECTIVE: To explore the role of natural killer T (NK T) cells in the
      pathogenesis of Graves' disease. METHODS: NK T cell deficient mice and wild
      BALB/c mice were immunized with cells expressing TSH receptor once every two
      weeks 6 times. Two weeks after the final immunization, the mice were killed and
      serum thyroxine levels, anti-TSH receptor antibodies and thyroid pathological
      changes were examined. RESULTS: The mean levels of TT(4) and TRAb in the
      immunized NK T cell deficient group were slightly elevated but significantly
      different from those of the non-immunized control group, while comparable to
      those in the immunized wild group. There were no significant changes of the
      activity levels of TSAb or TSBAb in the immunized NK T cell deficient mice
      compared to those in immunized wild control mice. Thyroids from immunized NK T
      cell deficient mice showed mild hypertrophy of some follicles as compared with
      non-immunized control mice. This change was comparable to immunized wild control
      mice. CONCLUSION: NK T cells may not be involved in the pathogenesis of Graves'
      disease.

PMID- 12215289
TI  - Five novel monoclonal antibodies to thymic epithelial cell surface antigens in
      rats.
AB  - OBJECTIVE: To establish monoclonal antibodies (mAbs) against thymic epithelial
      cells and study the function of epithelial cells during T-cell differentiation in
      the thymus. METHODS: Hybridomas secreting mAbs against thymic epithelial cells
      were derived by immunization of Balb/c mice with two thymic epithelial cell
      lines, TaD3 and FTE. The distribution of antigens recognized by these mAbs was
      detected by immunochemical staining and cytofluorographic analysis, and the
      molecular weight of the antigens by immunoblotting. RESULTS: Five specific
      monoclonal antibodies (mAb) were obtained. On the basis of their distribution in
      the thymus determined by immunochemical staining, mAb RE-4D8 was regarded as
      clusters of thymic epithelium staining (CTES) type IIA: mAb RE-12B2, which showed
      a unique distribution pattern only in the medulla, was CTES type V: mAb RE-5C6
      was CTES type IV: mAb RE-6D6 might be CTES type IIB: and mAb RE-1D4 was
      classified as type V. The molecular weight (MW) of antigen RE-4D8, RE-6D6 and RE
      12B2 were 120 kDa, 220 kDa and 35 kDa, respectively. Antigen RE-1D4 is a novel
      marker of cortical epithelium, several established thymic epithelial cell lines
      were classified and their original intrathymic locations were determined by these
      mAbs. Thymic cell lines, TuD3 and FTE were cortical phenotypes whereas TaD3 had a
      medullar phenotype. CONCLUSIONS: These mAbs clearly demonstrate the heterogeneity
      of the thymic epithelium; they could detect antigens not only in the cytoplasm
      but also on the surface of thymic epithelial cells. Our data suggest that these
      newly established mAbs may help elucidate the interaction between thymocytes and
      epithelial cells during T cell maturation.

PMID- 12215290
TI  - Changes in Ca2+-ATPase in a guinea pig endolymphatic hydrops model.
AB  - OBJECTIVE: To investigate the localization of Ca(2+)-ATPase (Ca(2+) pump) in the
      cochlear and its change after endolymphatic hydrops, and to study the
      relationship between compound action potential (CAP) threshold and the Ca(2+)
      ATPase activety. METHODS: The left endolymphatic sac was ablated to induce
      endolymphatic hydrops in fourteen healthy guinea pigs with normal action
      potential thresholds measured after a sliver ball electrode placed on the round
      window. Ca(2+)-ATPase activity was studied cytochemically using a lead citrate
      reaction in control and hydropic ears. The reaction product was lead phosphate
      particles as an expression of Ca(2+)-ATPase activity, observed with an eletron
      microscope. RESULTS: Ca(2+)-ATPase activity is mainly found on the endolymphatic
      surface of Reis sner's membrane, the stereocilia and cuticular plate of inner and
      outer hair cells, and along the infolded plasma membrane of strial marginal
      cells. CAP thresholds of filtered click are increased and Ca(2+)-ATPase activity
      significantly decreased after endolymphatic hydrops in the mentioned locations.
      CONCLUSIONS: CAP thresholds are increased and Ca(2+)-ATPase activity are
      significantly decreased in the cochlea after endolymphatic hydrops. These results
      suggest that there is a negative correlation between them.

PMID- 12215291
TI  - Stable expression of antisense hTR inhibits in vitro pancreatic cancer cell
      growth.
AB  - OBJECTIVE: To clarify growth inhibition in pancreatic cancer cells by
      interference with the hTR component of the telomerase reverse transcriptase
      enzymatic complex. METHODS: A 593 bp full length hTR cDNA was subcloned into a
      mammalian expression vector pcDNA3.1(-) in the antisense orientation to construct
      an antisense hTR expression plasmid. These were introduced into panc1 cells, a
      human pancreatic carcinoma cell line, by lipofectin and G418-resistant stable
      transformants were expanded. Resulting stable clones were screened for the
      presence of the hTR insert by PCR with T7 and BGH reverse primers located on the
      flanks of the multiclonal site of the pcDNA3.1 vector. Cell growth rate, hTR
      expression, telomerase activity and anchorage-independent growth properties were
      analyzed. RESULTS: Significant downregulation of endogenous hTR was evident in
      the antisense-hTR transformed cells and telomerase activity was markedly
      decreased compared to control cells in standard TRAP assays. Furthermore, cell
      proliferation and the anchorage-independent growth ability in antisense-hTR
      expressing cells were significantly decreased compared with control parental
      cells. However, no crisis or senescence phenomena were observed. CONCLUSIONS:
      These data indicate that hTR may be a critical component of human telomerase
      activity and suggest that downregulation of the RNA component of human telomerase
      is a possible target for anticancer strategies.

PMID- 12215292
TI  - Chromosome 14q may harbor multiple tumor suppressor genes in primary glioblastoma
      multiforme.
AB  - OBJECTIVE: To evaluate whether deletion of chromosome 14q is involved in the
      carcinogenesis of primary glioblastoma multiforme and to identify possibly common
      deletion regions. METHJODS: Fourteen fluorescent dye-labeled polymorphic markers
      were used and polymerase chain reaction-based microsatellite analysis was
      employed to investigate loss of heterozygosity (LOH) on chromosome 14q in 20
      primary glioblastoma multiforme (GBM). RESULTS: Ten of twenty (50%) GBM displayed
      LOH at one or more of the markers on chromosome 14q. Five tumors showed either
      LOH or non-informative on all markers tested. The most frequent LOH was observed
      at locus D14S65 (57.1%) on 14q32.1, and in the chromosomal region spanning from
      D14S63 (47.1%) to D14S74 (46.7%) on 14q23-31. None of the informative loci
      exhibited microsatellite instability. CONCLUSIONS: Allelic deletion on chromosome
      14q plays an important role in the pathogenesis of GBM.   Chromosomal regions at
      locus D14S65 on 14q32.1 and spanning from D14S63 to D14S74 on 14q23-31 may harbor
      multiple tumor suppressor genes associated with GBM.

PMID- 12215293
TI  - Adenoviral mediated suicide gene transfer in the treatment of pancreatic cancer.
AB  - OBJECTIVE: To determine the efficacy of adenovirus  mediated suicide gene
      transduction combined with prodrug 5-fluorocytosine (5FC) as a therapeutic
      protocol for pancreatic cancer. METHODS: Cytosine Deaminase(CD) gene was cloned
      into pAdTrack-CMV-CD, pAdTrack-CMV-CD and pAdEasy-1 were recombined in bacteria.
      The newly recombined adenovirus (Ad)-CD containing green fluorescent protein
      (GFP) were packaged and propagated in 293 cells and purified by cesium chloride
      gradient centrifugation. Human pancreatic carcinoma cell line-Patu8988 was
      infected with this virus, then 5FC was added. XTT assay was used to estimate
      relative numbers of viable cells. In vivo model of pancreatic cancer was
      established by injecting 1.0 x 10(7) Patu8988 cells subcutaneously in Balb/c nude
      mice. When tumors were palpable, Ad-CD was injected into each tumor and 5FC was
      administered. RESULTS: Positive clones were selected using endonuclease to digest
      the recombinants and the concentration of viral liquids containing the CD gene
      was 2 x 10(11) pfu /ml. Significant cytotoxic activity as shown for 5FC in the CD
      gene transduced 8988 cell line, while little effect was found in the
      nontransduced pancreatic carcinoma cells. Antitumor effect was observed in
      Patu8988 xenograft nude mice with in situ CD gene transduction. CONCLUSIONS: CD
      gene mediated by adenovirus has high infectivity and may be useful for gene
      therapy in pancreatic carcinoma. These data demonstrate the use of an enzyme
      prodrug strategy in experimental pancreatic cancer.

PMID- 12215294
TI  - Extracellular domain of kinase domain region mediated by adeno-associated virus
      inhibits growth and angiogenesis of bladder cancer in Balb-c mice.
AB  - OBJECTIVE: To verify whether the extracellular domain of kinase domain region
      (KDR) has anti-angiogenesis activity in vivo. METHODS: cDNA was cloned into adeno
      associated virus (AAV) vector pSNAV and transfected to baby hamster kidney (BHK)
      cells. Recombinant AAV was obtained from the cell culture supernatant after
      adding helper virus. Recombinant AAV-infected human bladder cancer EJ cell line
      (EJ cells) were injected subcutaneously into Balb-c nude mice. Tumor specimens
      were removed from the mice, paraffin-embedded and sliced, then stained by
      immunohistochemistry. Microvessel density (MVD) was determined under a
      microscope. RESULTS: The tumor volume developed by EJ cells transfected with the
      extracellular domain of KDR was significantly smaller (1.70 +/- 0.18 cm(3))
      compared with that in the control (5.62 +/- 0.67 cm(3)) (P < 0.05), although
      tumor developed to be detectable on almost the same time (14.7 +/- 2.4 days vs
      14.1 +/- 3.2 days). Further, MVD in the experimental group was lower than that in
      the control (41.3 +/- 4.8 vs 6.2 +/- 2.1, P < 0.05). CONCLUSION: The
      extracellular domain of KDR could be expressed in nude mouse bladder cancer
      tissue and inhibit tumor angiogenesis.

PMID- 12215295
TI  - Gene-viral vectors: a promising way to target tumor cells and express anticancer
      genes simultaneously.
AB  - OBJECTIVE: To develop a new kind of vector system called gene-viral vector, which
      combines the advantages of gene and virus therapies. METHODS: Using recombinant
      technology, an anti-tumor gene was inserted into the genome of replicative virus
      specific for tumor cells. The cell killing effect, reporter gene expression of
      the green fluorescence protein, anti-tumor gene expression of mouse interleukin
      12 (mIL-12) and replication of virus were observed by the methods of cell
      pathology, fluorescence microscopy, ELISA and electron microscopy, respectively.
      RESULTS: A new kind of gene-viral vector system of adenovirus, in which the E1b
      55 kD gene was deleted but the E1a gene was preserved, was constructed. The
      vector system, like the replicative virus ONYX-015, replicated and proliferated
      in tumor cells but not in normal ones. Our vector had an advantage over ONYX-015
      in that it carried different kinds of anti-tumor genes to enhance its therapeutic
      effect. The reporter gene expression of the green fluorescence protein in tumor
      cells was much better than the adenovirus vector employed in conventional gene
      the rapy, and the expression in our vector system was as low as or even less than
      that in the conventional adenovirus gene therapy system. Similar results were
      observed in experiments with this vector system carrying the anti-tumor gene mIL
      12. Replication and proliferation of the virus carrying the mIL-12 gene in tumor
      cells were confirmed by electron microscopy. CONCLUSIONS: Gene-viral vectors are
      new vectors with an anti-tumor gene inserted into the genome of replicative virus
      specific for tumor cells. Because of the specific replication and proliferation
      of the virus in tumor cells, expression of the anti-tumor gene is increased
      hundreds to thousands of times. This approach takes full advantages of gene
      therapy and virus therapy to enhance the effect on the tumor. It overcomes the
      disadvantages of conventional gene therapy, such as low transfer rate, low gene
      expression, lack of target tropism, and low anti-tumor activity. We believe that
      this is a promising means for future tumor treatment.

PMID- 12215296
TI  - Identification of Trichophyton rubrum by PCR  fingerprinting.
AB  - OBJECTIVE: To observe the unique DNA profile and the relationship between DNA
      profile and phenotype of Trichophyton rubrum,and establish an effective molecular
      method to identify T. rubrum. METHODS: Three primers, including (GACA)(4),
      (GTG)(5) and M13 core sequence (5'-GAGGGTG-GCGGTTCT-3'), were used to distinguish
      variations among 20 clinical isolates of T. rubrum and Trichophyton
      mentagrophytes. RESULTS: Different PCR-fingerprinting was seen between T. rubrum
      and T. mentagrophytes using three different primers. 2 stains of T. rubrum were
      identified among 6 supposed T. mentagrophytes. CONCLUSIONS: T. rubrum can be
      distinguished using PCR, and (GACA)(4) is the most suitable primer.

PMID- 12215297
TI  - Expression of telomerase genes in cancer development in atypical hyperplasia of
      the mammary duct.
AB  - OBJECTIVE: To investigate telomerase gene expression in precancerous mammary
      lesion, such as atypical ductal hyperplasia and breast cancer and to study the
      relationship between expression and malignant transformation. METHODS: Expression
      of human telomerase genes (hTR) and human reverse transcriptase gene (hTRT) in 76
      cases of mammary tissue was evaluated using in situ hybridization and included 50
      cases of mammary hyperplasia, 6 of which were benign hyperplasia, 9 were mild
      atypical hyperplasia, 12 were moderate atypical hyperplasia, 23 were severe
      atypical hyperplasia and 26 were mammary cancer. RESULTS: The expressions of hTR
      and hTRT mRNA were much weaker or negative in benign hyperplasia (16.6%, 0), weak
      to mild  moderate in atypical hyperplasia (22.2%, 11.1%, 33.3%, 25.0%), strong in
      severe atypical hyperplasia (60.9%, 52.1%), and significantly strong in mammary
      cancer (88.5%, 80.8%). The difference between mild-moderate atypical hyperplasia,
      invasive ductal carcinoma and severe atypical hyperplasia was significant (P <
      0.05) and the difference between severe atypical hyperplasia and intraductal
      carcinoma was not significant (P > 0.05). CONCLUSION: Telomerase genes (hTR and
      hTRT) expressions are related to the transformation of atypical hyperplasia.
      Activated telomerase may play a role in mammary cancer development.

PMID- 12215298
TI  - Detection of EP1 and FP receptor mRNAs in the iris-ciliary body using in situ
      hybridization.
AB  - OBJECTIVE: To determine the expression of E-prostanoid1 (EP(1)) and F-prostanoid
      (FP) receptor mRNAs in iris-ciliary bodies of the human eye using in situ
      hybridization. METHODS: EP(1) and FP receptor mRNAs were detected by riboprobes
      labeled with digoxigenin on paraffin sections of the iris-ciliary body tissue of
      the human eye using in situ hybridization. RESULTS: EP(1) and FP receptor mRNAs
      were highly expressed in blood vessels, muscles and the endothelia of the iris.
      EP(1) receptor hybridization signals were present in all muscle fibers of the
      ciliary body. Hybridization signal corresponding to FP receptor mRNA transcript
      was predominantly expressed in the circular muscle and in the collagenous
      connective tissues of the ciliary body. FP receptor mRNA was not detected in
      radial and longitudinal muscles. CONCLUSIONS: EP(1) and FP receptor mRNAs in
      human ocular tissues appear to be widely localized in the functional sites of the
      respective receptor agonists. Selective localization of EP(1) and FP receptor
      mRNAs in the circular muscles and collagenous connective tissues of the ciliary
      body suggests that EP(1) and FP receptors play an important role in enhancing
      uveoscleral outflow of aqueous humor.

PMID- 12215299
TI  - Effect of N,N'-dinitrosopiperazine on in vitro expression of human cytochrome
      P450 2E1.
AB  - OBJECTIVE: To establish an in vitro heterogeneous expression model of human
      CYP2E1 (hCYP2E1) cDNA and investigate the effect of the chemical carcinogenic N,
      N'-dinitrosopiperazine (DNP) on the expression of CYP2E1. METHODS: Exogenous
      hCYP2E1 was introduced into the mouse derived NIH3T3 cells using the
      lipofectamine transfection technique. Integration of exogenous hCYP2E1 gene was
      identified by PCR and Southern blot. After treatment with various concentration
      of ethanol and DNP on the transfected NIH3T3 cell cultures, RT-PCR and Western
      blot was applied to detect the expression level of CYP2E1. RESULTS: Two cell
      clones with integration and stable expression of exogenous hCYP2E1 were obtained
      and designated as NIH3T3-2E1-A4 and NIH3T3-2E1-A8 respectively. The expression of
      both hCYP2E1 mRNA and protein products was promoted after either ethanol or DNP
      treatment. CONCLUSION: The results suggested that the promoted expression of
      hCYP2E1 induced by DNP and /or ethanol is due to enhanced transcription. The
      mechanism of DNP carcinogenes is might be related to this in situ activated
      metabolism by CYP2E1.

PMID- 12215300
TI  - Fine mapping of susceptibility genes by Lewontin's linkage disequilibrium measure
      with application to Alzheimer's disease.
AB  - OBJECTIVES: To formulate an equation for fine mapping of disease loci under
      complex conditions and determine the marker-disease distance in a specific case
      using this equation. METHODS: Lewontin's linkage disequilibrium (LD) measure D'
      was used to formulate an equation for mapping disease genes in the presence of
      phenocopies, locus heterogeneity, gene-gene and gene-environment interactions,
      incomplete penetrance, uncertain liability and threshold, incomplete initial LD,
      natural selection, recurrent mutation, high disease allele frequency and unknown
      mode of inheritance. This equation was then used to determine the distance
      between a marker ( epsilon 4 within the apolipoprotein E gene, APOE) and
      Alzheimer's disease (AD) loci using published data. RESULTS: An equation was
      formulated for mapping disease genes under the above conditions.If these
      conditions are present but ignored, then recombination fraction theta between
      marker and disease loci will be either overestimated or estimated with little
      bias. Therefore, an upper limit of theta can be obtained. AD has been found to be
      associated with the marker allele epsilon 4 in Africans, Asians, and Caucasians.
      This suggests that the AD- epsilon 4 allelic LD predates the divergence of
      peoples occurring 100 000 years ago. With the age of AD- epsilon 4 allelic LD so
      estimated, the maximal distance was calculated to be 23.2 kb (mean 5.8 kb).
      CONCLUSIONS: (1) A method is developed for LD mapping of susceptibility genes.
      (2) A mutation within the APOE gene itself, among others, is responsible for the
      susceptibility to AD, which is supported by recent evidence from studies using
      transgenic mice.

PMID- 12215301
TI  - Mcl-1 mediates cytokine deprivation induced apoptosis of human myeloma cell line
      XG-7.
AB  - OBJECTIVE: To investigate apoptosis in XG-7, a human myeloma cell line, induced
      by IL-6 deprivation and the function of three anti-apoptotic Bcl-2 proteins (Bcl
      2, Bcl-kappa(L), Mcl-1) in the apoptotic process. METHODS: Apoptosis in XG-7
      myeloma cells induced by IL-6 withdrawal was determined by flow cytometry with
      propidium iodide (PI) nuclear staining. Expressions of three Bcl-2 proteins in XG
      7 cells were monitored by immunoblotting assay. RESULTS: In the absence of IL-6
      for a certain time, a significant percentage of apoptiotic XG-7 cells can be
      observed, as well as down-regulated expression of one of the three anti-apoptotic
      proteins (Mcl-1) in XG-7 cells. IL-6 re-stimulation in XG-7 cells following
      cytokine removal up-regulated the expression of Mcl-1 and inhibited cell
      apoptosis. CONCLUSION: Mcl-1,instead of Bcl-2 and Bcl-kappa(L), plays an
      important role in IL-6 deprivation induced apoptosis in XG-7 human myeloma cells.

PMID- 12215303
TI  - Comments on women's health and aging.

PMID- 12215302
TI  - Individual and societal forms of violence against women in the US and the
      developing world: an overview.

PMID- 12215305
TI  - Advances in polycystic ovary syndrome treatment: metformin and ovarian diathermy.
AB  - Polycystic ovary syndrome (PCOS) affects approximately 6% of women in their
      reproductive years. The symptoms of the syndrome are chronic anovulation and
      androgen excess. Infertility due to ovulatory dysfunction is a common problem for
      women with PCOS. Metformin, an antihyperglycemic agent, can correct the metabolic
      dysfunction that occurs with PCOS, and also stimulate folliculogenesis. The drug
      is effective alone and in combination with clomiphene citrate. An alternative
      option, ovarian diathermy, also promotes ovulation through changes in the
      intraovarian hormonal environment. Both techniques provide promising and
      effective alternatives for women with PCOS who do not respond to traditional oral
      ovulation induction agents.

PMID- 12215306
TI  - Male contraception.
AB  - From a public health perspective, the need for contraception has never been
      greater. Although the existing male-specific methods (withdrawal, condoms, and
      vasectomy) are safe and effective, increasing male options for fertility control
      could improve family planning. For new male contraceptive methods to have an
      impact, they must be acceptable to both men and women, as well as effective. A
      male hormonal method will likely come to market within the next 5 years. Other
      strategies such as contraceptive vaccines, and inhibitors of spermatogenesis and
      sperm motility, provide a potential for nonhormonal male contraceptives.

PMID- 12215307
TI  - How to treat a menopausal woman: a history, 1900 to 2000.
AB  - Over the course of the 20th century, physicians had a variety of hormonal
      treatments to offer their menopausal patients. This paper traces the development
      and deployment of these therapies, which ranged from desiccated ewe ovary to the
      modern estrogen replacement therapy. In addition, this paper demonstrates that
      women often medicated themselves at menopause, turning perhaps to Lydia Pinkham's
      vegetable tonic or the more modern Change-O-Life elixir. Finally, this paper
      discusses the larger societal approaches to eliminating menopausal symptoms.

PMID- 12215308
TI  - Osteoporotic fractures in older women.
AB  - A case review of postmenopausal osteoporosis is presented in the context of
      recent literature in the field. Given the case patient's high risk for future
      fracture, a thorough workup and pharmacologic intervention are reasonable.
      Etiology of the patient's disease is explored, particularly vitamin D
      insufficiency, low body weight, smoking history, celiac sprue, use of
      glucocorticoids, and estrogen status. Means of reducing fracture risk include
      lifestyle changes, calcium and vitamin D repletion, antiresorptive therapy, and
      patient education. Development of new therapies to further reduce fracture risk
      in such individuals, and efficient strategies to target interventions toward
      those at highest risk, are needed.

PMID- 12215309
TI  - Cardiovascular disease and the aging woman: overcoming barriers to lifestyle
      changes.
AB  - Coronary heart disease (CHD) is the leading cause of death in women aged 60 years
      and older, yet 40% of this group believe they are unlikely to have a heart
      attack. Recent data show that the lack of a low-risk lifestyle may account for
      approximately 82% of coronary events in women. Underappreciation of CHD risk may
      prevent aging women from making significant changes in dietary habits, activity
      levels, and tobacco use to decrease their risk. In addition, many physicians may
      not treat cardiovascular risk factors aggressively in middle-aged and older
      women, despite data from primary and secondary prevention trials supporting the
      efficacy of interventions. This article addresses age-related changes in
      cardiovascular risk factors in women, with a focus on lifestyle interventions.

PMID- 12215310
TI  - Medical issues and hormone replacement therapy.
AB  - The debate surrounding postmenopausal hormone replacement therapy (HRT) has
      become more contentious in the past decade. The relationship between HRT and
      venous thrombotic events has been confirmed, although the absolute risk is small.
      Evidence of a relationship between breast cancer and HRT is stronger. Randomized
      controlled trials reveal an association with cardiovascular events in women with
      known heart disease, a possibly diminished overall quality of life due to HRT,
      and worsening of urinary incontinence. There is also some evidence associating
      HRT with ovarian cancer. However, longitudinal studies continue to demonstrate
      over the long term that HRT use is associated with fewer cardiovascular events
      and a reduced risk of developing dementia. Future studies may show that a lower
      daily dose of HRT can reduce the risks while still providing benefit.

PMID- 12215311
TI  - What we know about estrogen's effect on the brain.
AB  - Cognitive impairment and Alzheimer's disease are growing problems as our
      population ages. Although estrogen appears to beneficially effect neurons,
      evidence that hormone therapy improves cognition or prevents dementia is limited.
      All studies are hampered by difficulties in strict dementia ascertainment and
      confounding due to cognitive testing while observational studies are biased by
      the healthy hormone therapy user effect. Does estrogen preserve cognition? Some
      studies demonstrated a small improvement in generally healthy women, but some
      found no effect. Does estrogen prevent Alzheimer's disease? Many case-control and
      two cohort studies reported a sizeable benefit of hormone therapy, but many did
      not adequately adjust for confounders and there are no randomized controlled
      trial data yet. Does estrogen improve function in women with Alzheimer's disease?
      A large randomized controlled trial demonstrated no beneficial effect of
      conjugated estrogen on clinical outcomes in women who already had mild to
      moderate Alzheimer's disease.

PMID- 12215312
TI  - DES exposure and the aging woman: mothers and daughters.
AB  - Diethylstilbestrol (DES), the first orally active artificial estrogen ever
      developed, was prescribed to several million pregnant women during the 1940s
      through the 1960s in the mistaken belief that it reduced the risk of miscarriage.
      In 1971, the US Food and Drug Administration contraindicated its use in pregnancy
      when DES was associated with the development of vaginal clear cell adenocarcinoma
      (CCA) in daughters exposed in utero. In daughters whose mothers took DES during
      pregnancy, the drug has been associated with congenital malformations of the
      reproductive tract, fertility problems, a possible increased risk of cervical
      carcinoma in situ, and a presumed lifetime risk of vaginal and cervical CCA. DES
      mothers have an increased risk of breast cancer (RR = 1.3). DES sons have an
      increased prevalence of urogenital anomalies, and a possible increased risk of
      testicular cancer.

PMID- 12215313
TI  - Perspectives from the world's largest Alzheimer's disease research conference:
      Stockholm, Sweden, July 2002.
AB  - The 8th International Conference on Alzheimer's Disease and Related Disorders,
      held in Stockholm, Sweden from July 20 to 25, 2002, provided an exciting forum
      for nearly 3700 researchers from 78 countries to present and discuss advances in
      dementia research on a worldwide stage. Hosted by the Alzheimer's Association
      (Chicago, IL), this largest dementia research conference ever held united
      experienced researchers and relative newcomers to the field to learn from one
      another, challenge one another's thinking, and explore new possibilities for
      collaboration. The 12-fold growth in attendance, up from 300 scientists at the
      1st International Research Conference in 1988, signals the increasing global
      importance of Alzheimer's disease in the research community as well as among
      policy makers and the general public. In fact, a recent survey of older Americans
      by the National Council on the Aging revealed that future memory loss was the
      number one health worry of the American elderly population.

PMID- 12215314
TI  - Vitrification can be more favorable than slow cooling.
AB  - OBJECTIVE: Cryopreservation of embryos and oocytes has become an essential
      service for infertility treatment. The clinical application of this technology
      should ensure optimal survival of the embryos and oocytes that are stored and
      subsequently thawed for transfer. The aim of this review is to compare the widely
      employed slow cooling procedures with vitrification to evaluate and recommend the
      more effective and safer procedure. DESIGN: The review is mainly based on a
      comparison of the principles, procedures, and results reported in the literature.
      A historical description of vitrification and personal experiences with this
      technology are also included. SETTING: University-based hospitals and private
      clinics that treat infertility and have published information on
      cryopreservation. PATIENT(S): Women being treated for infertility and
      reproductive technology clinics. INTERVENTION(S): The application of slow cooling
      involving a range of cooling rates is compared with vitrification using rapid and
      ultrarapid cooling in simple containers. The purpose of both techniques is the
      induction of a glasslike state in cells to protect them from damage by ice
      crystals. The early development of vitrification involved the use of long pre
      equilibration procedures. Improved methods resulted from the use of mixtures of
      penetrating and nonpenetrating solutes that are not toxic and a range of cooling
      rates. MAIN OUTCOME MEASURE(S): Reported number of pregnancies established after
      transfer of embryos that were cryopreserved by vitrification, or transfer of
      embryos derived from vitrified oocytes. RESULT(S): Both slow cooling and
      vitrification procedures have resulted in the successful cryopreservation of
      human embryos and oocytes. Both procedures have resulted in healthy births,
      although the slow cooling of oocytes gives very low success rates. Vitrification
      is a promising novel technique in assisted reproductive technology, but
      comparative success rates are yet to be established. CONCLUSION(S): Vitrification
      is a simple procedure that requires less time and is likely to become safer and
      more cost effective than slow cooling.

PMID- 12215315
TI  - Micromanipulation of gametes and embryos may be a risk for human germ-line gene
      transfer.

PMID- 12215316
TI  - Gender selection for nonmedical indications.

PMID- 12215317
TI  - Sex selection for gender variety by preimplantation genetic diagnosis.

PMID- 12215318
TI  - Effects of tibolone on plasma levels of nitric oxide in postmenopausal women.
AB  - OBJECTIVE: To determine the effects of tibolone on nitric oxide (NO) plasma
      levels in postmenopausal women. DESIGN: Randomized, double-blind, placebo
      controlled, cross-over trial. SETTING: Healthy volunteers in an academic research
      environment. PATIENT(S): Eighteen healthy women who have been in postmenopause
      for 1-4 years. INTERVENTION(S): Women received either tibolone 2.5 mg/day (group
      A) or placebo (group B) for 1 month; then the treatment was inverted for the
      second month. MAIN OUTCOME MEASURE(S): Plasma concentration of NO stable
      oxidation products and blood pressure were evaluated at baseline, month 1, and
      month 2. RESULT(S): Baseline concentration of NO metabolites were similar in both
      groups. At month 1, mean concentration of NO metabolites increased significantly
      in group A alone. At the end of month 2, NO metabolite levels in group A returned
      to baseline, whereas in group B they increased significantly. CONCLUSION(S):
      Tibolone induced a sustained increase in plasma levels of NO in postmenopausal
      women, suggesting that tibolone may exert a direct cardiovascular protective
      effect in postmenopausal women.

PMID- 12215319
TI  - Effects of oral raloxifene on serum estradiol levels and other markers of
      estrogenicity.
AB  - OBJECTIVE: To determine the effects of raloxifene hydrochloride, 60 mg/d, on
      serum levels of E(2), estrone, sex steroid-binding globulin, thyroxine-binding
      globulin, and follicle-stimulating hormone (FSH) in postmenopausal women. DESIGN:
      Randomized placebo-controlled study at 16 centers in the United States.
      PATIENT(S): Ninety three women 42 to 80 years of age who were at least 2 years
      postmenopausal. INTERVENTION(S): Raloxifene (n = 47) or placebo (n = 46) for 3
      months. MAIN OUTCOME MEASURE(S): Levels of E(2), estrone, sex steroid-binding
      globulin, thyroxine-binding globulin, and FSH were measured at baseline and after
      3 months of therapy. RESULT(S): Raloxifene increased serum levels of sex steroid
      binding globulin and thyroxine-binding globulin and decreased FSH levels compared
      with placebo. Levels of E(2) and estrone were unaffected. CONCLUSION(S): In
      postmenopausal women, raloxifene (60 mg/d) did not increase serum estrogen
      levels; however, it increased levels of sex steroid-binding globulin and
      thyroxine-binding globulin and decreased FSH levels.

PMID- 12215320
TI  - Inter- and intrafamilial variability in premature pubarche and polycystic ovary
      syndrome.
AB  - OBJECTIVE: To ascertain the extent of phenotypic heterogeneity for premature
      pubarche and polycystic ovary syndrome between and within families. DESIGN:
      Association study. SETTING: Academic research environment. PATIENT(S): Three
      families in which the propositus had presented with either premature pubic hair
      or adolescent hyperandrogenism. INTERVENTION(S): Detailed medical histories,
      hormone determinations, and genotype analyses. MAIN OUTCOME MEASURE(S): Clinical
      phenotype. Genotypes for CYP21, HSD3B2, G972R variant of IRS-1, N363S variant of
      GRL, W64R variant of ADRB3, CAG repeat in exon 1 of AR, MspAI polymorphism in
      CYP17, and R264C variant of CYP19. RESULT(S): Significant phenotypic and genetic
      heterogeneity was observed both within and between families. In one family, CYP21
      and IRS-1 variants were observed to co-segregate with symptoms of androgen excess
      and obesity. No genetic markers were consistently noted to associate with
      clinical features of hyperandrogenism in the other two families. CONCLUSION(S):
      The difficulties in classifying female family members as clearly affected or
      unaffected and lack of definitive male phenotype complicate the use of linkage
      analysis to identify the polycystic ovary syndrome genes. Each family is best
      considered on an individual basis to identify genetic markers that segregate with
      the clinical features of androgen excess.

PMID- 12215321
TI  - Evidence for competing effects of body mass, hyperinsulinemia, insulin
      resistance, and androgens on leptin levels among lean, overweight, and obese
      women with polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate the relationships between leptin, body composition,
      insulin resistance, androgens, and reproductive indices among women with
      polycystic ovary syndrome (PCOS). DESIGN: Matched case-control study. SETTING:
      Academic reproductive endocrine practice; school of public health. PATIENT(S):
      Forty-six Caucasian women with PCOS and 46 population-based controls matched by
      age and body mass index (BMI). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Leptin, insulin, androgenic hormones, body composition parameters; reproductive
      parameters. RESULT(S): Overall, leptin levels among women with PCOS did not
      differ significantly from those of control women (20.4 +/- 14.9 vs. 21.9 +/- 14.3
      ng/mL). However, within the lowest BMI tertile, women with PCOS had significantly
      lower leptin levels (9.6 vs. 18.3 ng/mL), comparable insulin, and higher
      testosterone concentrations than controls of similar body mass. Within the
      overweight and obese subgroups, both insulin and testosterone levels were
      increased among women with PCOS; leptin levels, although higher among obese
      cases, were not statistically different than those in controls. CONCLUSION(S):
      Below a certain BMI, hyperandrogenic women with PCOS have lower leptin levels
      than controls. Conversely, overweight and obese PCOS subjects appear to produce
      insufficient leptin for a given fat mass, relative to the degree of
      hyperinsulinemia, potentially because of the competing effects of adipocyte
      insulin resistance and androgens on leptin.

PMID- 12215322
TI  - Increased prevalence of insulin resistance in women with a history of recurrent
      pregnancy loss.
AB  - OBJECTIVE: To determine whether insulin resistance is associated with recurrent
      pregnancy loss (RPL). DESIGN: Single center, case-controlled, prospective study.
      SETTING: University-associated reproductive endocrinology clinical practice.
      PATIENT(S): Seventy-four nonpregnant, nondiabetic women with RPL. Controls were
      74 fertile, nonpregnant, nondiabetic women without RPL who had at least one live
      infant, and were matched by age, race, and body mass index (BMI).
      INTERVENTION(S): Both groups consented to obtaining fasting insulin and glucose
      levels. MAIN OUTCOME MEASURE(S): Insulin resistance was defined as a fasting
      insulin level >20 microU/mL or a fasting glucose to insulin ratio of <4.5.
      RESULT(S): Among the 74 women with RPL, 20 (27.0%) demonstrated insulin
      resistance, whereas only 7 of 74 (9.5%) of the matched controls were insulin
      resistant (odds ratio 3.55; 95% confidence interval 1.40-9.01). The RPL and
      control groups were similar with respect to age, ethnicity, and BMI. The RPL and
      control groups had similar fasting glucose levels and glucose-to-insulin ratios.
      However, fasting insulin levels > or =20 microU/mL were statistically different
      between the two groups (odds ratio 3.92). CONCLUSION(S): Women with RPL have a
      significantly increased prevalence of insulin resistance when compared with
      matched fertile controls.

PMID- 12215323
TI  - Effect of cigarette smoking on levels of seminal oxidative stress in infertile
      men: a prospective study.
AB  - OBJECTIVE: To investigate levels of seminal oxidative stress (OS) and sperm
      quality in a group of infertile men with a history of cigarette smoking. DESIGN:
      A prospective clinical study. SETTING: Male infertility clinic, Urological
      Institute, the Cleveland Clinic Foundation, Cleveland, Ohio. PATIENT(S):
      Infertile men who smoked cigarettes (n = 20), infertile men who were nonsmokers
      (n = 32), and healthy nonsmoking donors (n = 13). INTERVENTION(S): Genital
      examination, standard semen analysis, sperm DNA damage. MAIN OUTCOME MEASURE(S):
      Levels of seminal reactive oxygen species (ROS) and total antioxidant capacity
      (TAC) measured by a chemiluminescence assay and seminal OS assessed by
      calculating a ROS-TAC score. Sperm DNA damage was measured by sperm chromatin
      structure assay. RESULT(S): Smoking was associated with a 48% increase in seminal
      leukocyte concentrations (P<.0001), a 107% increase in ROS levels (P=.001), and a
      10-point decrease in ROS-TAC scores (P=.003). Differences in standard sperm
      variables and DNA damage indices between the infertile smokers and infertile
      nonsmokers were not statistically significant. CONCLUSION(S): Infertile men who
      smoke cigarettes have higher levels of seminal OS than infertile nonsmokers.
      Given the potential adverse effects of seminal OS on fertility, physicians should
      advise infertile men who smoke cigarettes to quit.

PMID- 12215324
TI  - Validation of a model predicting spontaneous pregnancy among subfertile untreated
      couples.
AB  - OBJECTIVE: To provide external validation of the Eimers model, which predicts
      spontaneous pregnancy among subfertile couples within the first year after the
      definitive establishment of the diagnostic category. DESIGN: Live birth rates
      predicted by an adapted version of the Eimers model were tested against observed
      live birth rates in a Canadian cohort study. SETTING: Fertility clinics in
      university medical centers. PATIENT(S): One thousand sixty-one couples consulting
      for subfertility due to cervical hostility, male subfertility, or unexplained
      subfertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We measured the
      discriminative ability and reliability of the predictions from the model.
      RESULT(S): The live birth rate was lower in the Canadian population than in the
      Eimers population. Overall, the prognostic effect of the predictors did not
      differ significantly in both populations. The model showed moderate predictive
      power in the Canadian population. With adjustment of the average live birth rate,
      the reliability of the model was satisfactory. CONCLUSION(S): The Eimers model
      gave reliable spontaneous pregnancy predictions in the Canadian validation
      population after adjustment of the average live birth rate.

PMID- 12215325
TI  - Use of the internet as the only outlet for talking about infertility.
AB  - OBJECTIVE: To gather information about demographic characteristics, medical
      status, mode of Internet participation, and psychological well-being of
      participants whose only outlets (OOs) for talking about infertility are Internet
      medical and support forums and to compare them with persons who have additional
      outlets (AOs). DESIGN: Prospective Internet-based survey. SETTING: Website of a
      nonprofit international infertility organization. PATIENT(S): Five hundred eighty
      nine persons submitting fully completed surveys. INTERVENTION(S): Internet-based
      survey with 134 items. MAIN OUTCOME MEASURE(S): Survey of types of Internet
      participation, benefits of participation, self-assessed ability to cope with
      aspects of infertility, perceived stress, perceived support from relatives and
      friends, and 21-item Beck Depression Inventory (BDI), which is an instrument
      designed to measure depressive symptomatology. RESULT(S): Only-outlet and AO
      participants were comparable in their medical history and treatments. Only-outlet
      participants had less formal education, were less wealthy, and more likely to be
      homemakers. Compared with AO participants, OO participants were more depressed
      and got less real-world support while feeling more supported on the Internet.
      CONCLUSION(S): Used properly, the Internet can help people facing infertility by
      educating, empowering, and diminishing their feelings of depression. But the
      Internet can also be used inappropriately to withdraw from real-world
      interactions.

PMID- 12215326
TI  - Increased frequency of female partner chromosomal abnormalities in patients with
      high-order implantation failure after in vitro fertilization.
AB  - OBJECTIVE: To find the type and frequency of chromosomal abnormalities in a
      selected group of high-order implantation failure (> or =6 IVF trials and > or
      =15 transferred embryos) and to evaluate its impact on pregnancy outcome. DESIGN:
      A retrospective study. SETTING: In vitro fertilization (IVF) unit in a university
      affiliated hospital. PATIENT(S): Sixty-five couples with high-order implantation
      failure in IVF and embryo transfer. INTERVENTION(S): In vitro
      fertilization/embryo transfer (ET), work-up for implantation failure, cytogenetic
      analysis of the couple. MAIN OUTCOME MEASURE(S): We studied the type and
      frequency of chromosomal changes, quality of embryos, cumulative pregnancy rates,
      and pregnancy outcome. RESULT(S): The mean number of treatment cycles per
      patient, before karyotyping was 7.8 +/- 2.4 (range: 6 to 16 cycles). The mean
      cumulative number of all transferred embryos per patient was 25.7 +/- 10.3
      (range: 9 to 65 embryos). Chromosomal abnormalities were found in 10 of 65
      (15.4%) cases: translocations in six, mosaicism in two, and inversion or deletion
      in another two. The morphologic characteristics of the transferred embryos and
      the cumulative pregnancy rates were similar in patients with implantation failure
      with and without chromosomal changes. Three of the 16 patients with abnormal
      karyotype delivered and three miscarried within a follow-up period of 1 year.
      CONCLUSION(S): A high frequency of chromosomal aberrations was found in a
      selected group of high-order implantation failures, a similar frequency to
      recurrent miscarriages. Karyotyping is recommended as part of the work-up for
      repeated implantation failure in assisted reproduction. Treatment options include
      further IVF trials, preimplantation genetic diagnosis, or oocyte donation,
      tailored according to the type of chromosomal change. An international registry
      should be considered to assist in counseling these patients.

PMID- 12215327
TI  - Efficacy and safety of highly purified menotropin versus recombinant follicle
      stimulating hormone in in vitro fertilization/intracytoplasmic sperm injection
      cycles: a randomized, comparative trial.
AB  - OBJECTIVE: To demonstrate that highly purified human menopausal gonadotropin (HP
      hMG) is as efficient and safe as recombinant FSH in females undergoing in vitro
      fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycles.
      DESIGN: Multinational, open label, randomized, parallel group, comparative phase
      III trial. SETTING: In 22 centers across six countries; Belgium (1 center),
      Germany (6 centers), Israel (6 centers), The Netherlands (2 centers), Switzerland
      (1 center) and the United Kingdom (6 centers). PATIENT(S): A total of 781 women
      were enrolled between May 1999 and November 2000. INTERVENTION(S): In the all
      patients-treated population, 373 patients received HP-hMG and 354 received
      recombinant FSH. A long protocol GnRH agonist regimen was used. MAIN OUTCOME
      MEASURE(S): The primary end point was ongoing pregnancy rate following one
      IVF/ICSI treatment cycle. Safety was assessed as a secondary end point.
      RESULT(S): Ongoing pregnancy rates 10 weeks after ovum pickup in the per-protocol
      population were 25% (n = 85/344) in the HP-hMG group and 22% (n = 71/317) in the
      recombinant FSH group. The incidence of ovarian hyperstimulation syndrome,
      miscarriage, adverse events, and injection site reactions (tolerability) were
      similar in both treatment groups. CONCLUSION(S): We found HP-hMG to be as
      effective as recombinant FSH in terms of ongoing clinical pregnancy. Both
      treatments have a similar safety/tolerability profile.

PMID- 12215328
TI  - Administration of methylprednisolone to prevent severe ovarian hyperstimulation
      syndrome in patients undergoing in vitro fertilization.
AB  - OBJECTIVE: To determine whether administration of methylprednisolone to high-risk
      women undergoing IVF/ICSI helps reduce the development of OHSS. DESIGN:
      Retrospective clinical controlled study. SETTING: IVF unit. PATIENT(S): One
      thousand ten women who underwent IVF/ICSI from January 9, 1997, to December 31,
      1999. Ninety-one patients who were at high risk for OHSS were identified by using
      standard criteria. INTERVENTION(S): Methylprednisolone, 16 mg/d starting on day 6
      of the stimulation and tapered after the first pregnancy test (day 13 after
      embryo transfer). MAIN OUTCOME MEASURE(S): Occurrence of OHSS. RESULT(S): A
      significantly lower proportion of methylprednisolone recipients than untreated
      participants developed OHSS (10.0% vs. 43.9%). Treatment recipients had more
      oocytes retrieved and more embryos fertilized than did untreated participants.
      Methylprednisolone treatment was equally effective in preventing OHSS in all
      causes of infertility and was effective independent of the number of IVF trials
      and pregnancy rates. CONCLUSION(S): Treatment with methylprednisolone appears to
      reduce the risk for OHSS. This treatment thus helps to avoid hospitalization,
      reduces cycle cancellations, and improves the cost-effectiveness of IVF cycles.

PMID- 12215329
TI  - Transabdominal ultrasound-guided embryo transfer does not increase pregnancy
      rates in oocyte recipients.
AB  - OBJECTIVE: To determine whether transabdominal ultrasound guidance during embryo
      transfer (ET) is a useful tool for increasing pregnancy rates in patients
      undergoing oocyte donation. DESIGN: Prospective, randomized, controlled trial.
      SETTING: In vitro fertilization academic center. PATIENT(S): Three hundred
      seventy-four infertile patients undergoing oocyte donation. INTERVENTION(S):
      Transabdominal ultrasound-guided ET. MAIN OUTCOME MEASURE(S): We measured the
      pregnancy rate and implantation rate after transabdominal ultrasound-guided ET
      versus the rates in a control group who did not receive transabdominal ultrasound
      guided ET. RESULT(S): Clear visualization at ultrasound during ET was achieved in
      90.8% of the patients who had ultrasound-guided ET. A similar number of easy
      transfers were performed in both the ultrasound-guided and the control groups
      (84.5% vs. 86.6%). The pregnancy rate was comparable between the groups (59.9%
      ultrasound vs. 55.1% control), as was the implantation rate (30.6% ultrasound vs.
      26.3% control). No differences were found in the miscarriage rate (10.7%
      ultrasound vs. 9.1% control) or in the multiple pregnancy rate (21.4% ultrasound
      vs. 22.5% control). Although all ectopic pregnancies occurred in the group that
      did not receive ultrasound guidance, the differences were not statistically
      significant (0 vs. 2.7%). CONCLUSION(S): We could not show any benefit in terms
      of pregnancy rate in oocyte recipients for whom ET was performed under direct
      transabdominal ultrasound visualization of the endometrial cavity. There was a
      lower ectopic pregnancy rate when ultrasound guidance was used, but this rate was
      not statistically significant in comparison with the pregnancy rate without
      ultrasound guidance.

PMID- 12215330
TI  - Serum human chorionic gonadotropin measurements may predict pregnancy outcome and
      multiple gestation after in vitro fertilization.
AB  - OBJECTIVE: To predict pregnancy outcome and multiple gestation using a common
      parameter by which hCG values are made comparable independently of the day of
      blood sampling. DESIGN: Retrospective study. SETTING: University-based IVF
      program. PATIENTS: One hundred twenty IVF pregnancies conceived between November,
      1995 and August, 1999. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Early
      pregnancy loss (preclinical and first trimester abortions, ectopic pregnancies)
      or ongoing pregnancies (singleton and multiple deliveries, second trimester
      abortions). Day 11 hCG levels were calculated assuming an exponential increase of
      hCG values in early pregnancy. Receiver-operating characteristic analysis was
      used to determine cut-off levels with the best sensitivity and specificity for
      the prediction of pregnancy outcome. RESULTS: Serum hCG levels in the group of
      early pregnancy loss were significantly lower than in ongoing pregnancies. A cut
      off level of 50 IU/L predicts pregnancy outcome with a sensitivity of 75% and a
      specificity of 81%, while an hCG value >135 IU/L predicts a multiple ongoing
      pregnancy with a sensitivity of 80% and a specificity of 88%. CONCLUSION: After
      IVF, early pregnancy loss or multiple gestation may be predicted with high
      sensitivity and specificity by using cut-off values of serum hCG derived from two
      measurements independently of the day of blood sampling.

PMID- 12215332
TI  - Spontaneous pregnancies in couples who discontinued intracytoplasmic sperm
      injection treatment: a 5-year follow-up study.
AB  - OBJECTIVE: To analyze the occurrence of deliveries after spontaneous conception
      in patients who have discontinued unsuccessful intracytoplasmic sperm injection
      (ICSI) treatment. DESIGN: Cohort follow-up study. SETTING: Tertiary referral
      center. PATIENT(S): Between July 1992 and December 1993, 200 Belgian women
      younger than 37 years underwent 433 consecutive unsuccessful ICSI cycles with
      freshly ejaculated sperm and eventually discontinued their treatment.
      INTERVENTION(S): Ultrasound-guided oocyte retrieval and ICSI. MAIN OUTCOME
      MEASURE(S): Delivery after 25 weeks following a spontaneous pregnancy. RESULT(S):
      The mean age at the time of the last oocyte pick-up was 31.0 +/- 3.9 years. The
      mean time interval between the last ICSI and the end of the follow-up period was
      47.7 +/- 12.1 months. Twenty-three spontaneous pregnancies ending in delivery
      after 25 weeks were observed (11.5%). The cumulative delivery rate reached a
      plateau of 10% after 36 months of follow-up. The mean time interval (from last
      oocyte retrieval) for spontaneous pregnancy to occur after discontinuing ICSI
      treatment was 20.2 +/- 13.7 months. Proportional hazards analysis showed that
      delivery rate was reduced by 2.0% per year of infertility. CONCLUSION(S): This
      study suggests that duration of infertility appears to be predictive of the
      likelihood of live delivery after spontaneous conception following an
      unsuccessful ICSI treatment.

PMID- 12215331
TI  - First clinical application of comparative genomic hybridization and polar body
      testing for preimplantation genetic diagnosis of aneuploidy.
AB  - OBJECTIVE: To develop a preimplantation genetic diagnosis (PGD) protocol that
      allows any form of chromosome imbalance to be detected. DESIGN: Case report
      employing a method based on whole-genome amplification and comparative genomic
      hybridization (CGH). SETTING: Clinical IVF laboratory. PATIENT(S): A 40-year-old
      IVF patient. INTERVENTION(S): Polar body and blastomere biopsy. MAIN OUTCOME
      MEASURE(S): Detection of aneuploidy. RESULT(S): Chromosome imbalance was detected
      in 9 of 10 polar bodies. A variety of chromosomes were aneuploid, but chromosomal
      size was found to be an important predisposing factor. In three cases, the
      resulting embryos could be tested using fluorescence in situ hybridization, and
      in each case the CGH diagnosis was confirmed. A single embryo could be
      recommended for transfer on the basis of the CGH data, but no pregnancy ensued.
      CONCLUSION(S): Evidence suggests that preferential transfer of chromosomally
      normal embryos can improve IVF outcomes. However, current PGD protocols do not
      allow analysis of every chromosome, and therefore a proportion of abnormal
      embryos remains undetected. We describe a method that allows every chromosome to
      be assessed in polar bodies and oocytes. The technique was accurate and allowed
      identification of aneuploid embryos that would have been diagnosed as normal by
      standard PGD techniques. As well as comprehensive cytogenetic analysis, this
      protocol permits simultaneous testing for multiple single-gene disorders.

PMID- 12215333
TI  - Inclusion of heterozygotes for cystic fibrosis in the egg donor pool.
AB  - OBJECTIVE: To describe and discuss our experience with cystic fibrosis (CF)
      carrier testing in a donor egg program. DESIGN: Retrospective review. SETTING:
      Community hospital-based assisted reproductive technology (ART) program.
      PATIENT(S): Forty anonymous white oocyte donor applicants. INTERVENTION(S):
      Testing with a DNA mutation analysis panel. MAIN OUTCOME MEASURE(S): Frequency of
      heterozygotes for CF mutation among the donor applicants and the likelihood of
      carriers and noncarriers being selected by recipients. RESULT(S): Five of 40 egg
      donor applicants (12.5%) were found to be heterozygous for a CF mutation; 35
      women (87.5%) tested negative. Two of the five CF carriers (40.0%) were selected
      by five recipient couples and underwent four donation cycles after the
      recipients' male partners tested negative. Twenty-nine of the 35 noncarrier
      donors (82.9%) were matched and underwent 81 egg donation cycles. The likelihood
      of being selected was lower for CF carriers than for noncarriers. CONCLUSION(S):
      Our experience strongly supports the recommendation of routine CF testing of
      prospective white egg donors. Whereas heterozygosity lowers the probability of a
      donor being matched, it need not exclude her from the donor pool provided the
      recipient's partner is not a carrier. Empowering recipients to choose their own
      donors, focused patient education, and genetic counseling with precise
      determination of residual risk are important prerequisites for inclusion of CF
      carriers.

PMID- 12215334
TI  - Multifetal pregnancy in older women and perinatal outcomes.
AB  - OBJECTIVE: To examine multifetal pregnancy in older women and perinatal outcomes.
      DESIGN: A cross-sectional study. SETTING: A nationwide vital registry.
      PATIENT(S): A national population-based database that links the live birth,
      fetal, and infant death certificates reported of multiple gestations in the
      United States from 1995 to 1997. It includes 155,777 twin and 5,630 triplet
      pregnancies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Very preterm birth
      (<33 weeks), very low birthweight (<1,500 g), and perinatal and infant deaths.
      RESULT(S): Compared with those with singleton pregnancies, women with multifetal
      gestation tended to be older, non-Hispanic white, better educated, married, and
      nulliparous and to have earlier and more frequent prenatal care. Pregnancies
      conceived by assisted reproductive technology accounted for an increasing number
      of multiple gestations in older women. In women with lower socioeconomic status,
      older age was associated with higher risks of poor perinatal outcomes in twin
      pregnancy (relative risks ranging from 1.0 to 1.9 with a dose-response pattern).
      However, in women with higher socioeconomic status, older women did not have a
      higher risk of poor perinatal outcomes than younger women. CONCLUSION(S): The
      effect of older maternal age on perinatal outcomes in multifetal pregnancies may
      have been altered by assisted reproductive technology, frequent prenatal
      surveillance, and advanced neonatal care.

PMID- 12215335
TI  - Molecular progress in infertility: polycystic ovary syndrome.
AB  - OBJECTIVE: To review the evidence that polycystic ovary syndrome is a genetic
      disease. DESIGN: Review of published literature. RESULTS: The existing literature
      provides a strong basis for arguing that PCOS clusters in families. However, the
      mode of inheritance of the disorder is still uncertain, although the majority of
      studies are consistent with an autosomal dominant pattern, modified perhaps by
      environmental factors. In addition, studies on PCOS cells (theca, muscle, and
      adipocytes) in culture have documented a persistent biochemical and molecular
      phenotype that distinguishes them from normal cells. Although several loci have
      been proposed as PCOS genes including CYP11A, the insulin gene, and a region near
      the insulin receptor, the evidence supporting linkage is not overwhelming. The
      strongest case can be made for the region near the insulin receptor gene, as it
      has been identified in two separate studies. However, the responsible gene at
      chromosome 19p13.3 remains to be identified. Association studies have provided a
      number of potential loci with genetic variants that may create or add to a PCOS
      phenotype, including Calpain 10, IRS-1 and -2, and SHBG. CONCLUSIONS:
      Collectively, these findings are consistent with the concept that a gene or
      several genes are linked to PCOS susceptibility. Because the mutations/genotypes
      associated with PCOS are rare, and their full impact on the phenotype
      incompletely understood, routine screening of women with PCOS or stigmata of PCOS
      for these genetic variants is not indicated at this time. Currently the treatment
      implications for individually identified genetic variants is uncertain and must
      be addressed on a case by case basis.

PMID- 12215336
TI  - Hydrosalpinx fluid diminishes endometrial cell HOXA10 expression.
AB  - OBJECTIVE: To determine the effect of hydrosalpinx fluid on the expression of
      HOXA10, an essential regulator of endometrial receptivity. DESIGN: In vitro
      study. SETTING: Academic medical center. PATIENT(S): Patients with unilateral or
      bilateral hydrosalpinx. INTERVENTION(S): Hydrosalpinx fluid was aspirated from 10
      patients at laparoscopy. The fluid was serially diluted in minimum essential
      medium. Ishikawa cells (an endometrial adenocarcinoma cell line, representative
      of endometrial epithelium) were incubated with this fluid at concentrations of
      10% and 50% for 48 hours. Cells were also incubated in undiluted minimum
      essential medium (MEM) and in 10% serum as controls. After incubation, the cells
      were lysed in Trizol, and total RNA was extracted and analyzed by Northern blot
      using a 32P-labeled HOXA10 riboprobe. A 32P-labeled G3PDH probe was used as a
      control for loading. MAIN OUTCOME MEASURE(S): HOXA10 mRNA expression. RESULT(S):
      HOXA10 mRNA expression in endometrial cells decreased with increasing
      concentrations of hydrosalpinx fluid. Densitometric analysis of the northern blot
      revealed that HOXA10 mRNA expression was different from control at both
      concentrations (P<.007). CONCLUSION(S): HOXA10 is necessary for implantation in
      the murine model. HOXA10 expression is diminished by hydrosalpinx fluid. This
      effect on HOXA10 is a potential molecular mechanism by which implantation rates
      are diminished in women with hydrosalpinges.

PMID- 12215337
TI  - Expression of von Willebrand's factor, CD34, CD31, and vascular endothelial
      growth factor in uterine leiomyomas.
AB  - OBJECTIVE: To compare the vascular parameters of uterine leiomyomas and normal
      myometrium, to correlate these parameters with vascular endothelial growth factor
      (VEGF) expression and clinical/pathological parameters, and to compare vascular
      parameters according to the endothelial markers used. DESIGN: An
      immunohistochemical technique was applied to formalin-fixed paraffin-embedded
      tissue samples, using antibodies against von Willebrand's factor (FvW), CD34,
      CD31, and VEGF. The intratumoral vascular area (VA), microvessel density (MVD),
      and vascular luminal area (VLA) were determined with an image analyser. SETTING:
      University teaching hospital. PATIENT(S): Thirty-two patients with uterine
      leiomyomas underwent conservative surgery. Twenty leiomyoma-free patients
      undergoing hysterectomy were the controls. INTERVENTION(S): Immunohistochemical
      and morphometrical analysis. MAIN OUTCOME MEASURE(S): Measurements of VA, MVD,
      and VLA. RESULT(S): The CD34 labeling showed decreased VA in myomas compared with
      myometrium. Decreased MVD and an increased VLA in myomas were found with FvW and
      CD34 labeling. The VA, MVD, and VLA were not related to VEGF expression or to
      clinical/pathological parameters. Similar results for VA and MVD were obtained
      with FvW and CD34 labeling. CONCLUSION(S): Leiomyomas have a smaller vascular
      area, a lower microvessel density, and a higher vascular luminal area than normal
      myometrium.

PMID- 12215338
TI  - Role of nitric oxide and bcl-2 family genes in the regulation of human
      endometrial apoptosis.
AB  - OBJECTIVE: To investigate the role of nitric oxide (NO) and death regulatory
      genes, bcl-2 and bax, in human endometria apoptosis. DESIGN: Expression of bcl-2,
      bax, NO synthases (NOS), and the apoptotic effect of L-arginine on endometrial
      explants in vitro. SETTING: Prospective study. PATIENT(S): Thirty-seven
      eumenorrheic women. INTERVENTION(S): Endometrial samples were obtained with
      Pipelle suction curette after women signed institutional informed consent forms.
      MAIN OUTCOME MEASURE(S): DNA fragmentation (TUNEL), immunohistochemistry, and
      reverse transcription polymerase chain reaction. RESULT(S): Apoptosis was
      detected in mid and late secretory endometria. L-arginine induced an increase in
      apoptosis in stroma (threefold), glands (eightfold), and surface epithelia
      (fourfold) in proliferative but not secretory endometria explants. Immunostaining
      of Bcl-2 was almost absent in the secretory endometria, whereas Bax increased in
      the stroma at the end of the menstrual cycle, coincident to the decrease in the
      bcl-2/bax mRNA relative ratio (P<.05) observed in secretory endometria.
      CONCLUSION(S): The induction of DNA fragmentation by L-arginine on proliferative
      endometria suggests that NO may be involved in the endometrial apoptotic process,
      whose control may be related predominantly to the changes of Bcl-2 expression.

PMID- 12215339
TI  - Retinoids and steroids regulate menstrual phase histological features in human
      endometrial organotypic cultures.
AB  - OBJECTIVE: To determine whether organotypic cultures of human endometrium can be
      manipulated with hormones to exhibit histological features resembling different
      menstrual cycle phases. DESIGN: Human menstrual cells were collected and cultured
      in monolayer and organotypic cultures. SETTING: Healthy volunteer in an academic
      research environment. PATIENT(S): An individual premenopausal woman.
      INTERVENTION(S): Endometrial cultures were grown in collagen gels for 4 weeks,
      and exposed to various steroid and retinoid treatments. MAIN OUTCOME MEASURE(S):
      Histological features and expression of cytokeratins, vimentin, and reticulin.
      RESULT(S): Cultures developed multiple glands and surface epithelium that
      exhibited positive cytokeratin and negative vimentin staining. Single stromal
      cells inside the collagen exhibited negative cytokeratin and positive vimentin
      staining. Networks of reticulin fibers produced by the cells were increased by
      estrogen, decreased by progesterone, and unaffected by retinoids. Contraction of
      the collagen gels was inhibited by retinoids that activated retinoic acid
      receptors (RARs), but not by a retinoid specific for retinoid X receptors (RXRs).
      The combination and timing of retinoid and steroid hormone treatments were
      demonstrated to induce tissue architecture and histological features that
      resembled either proliferative or secretory phases. CONCLUSION(S): Growth of
      menstrual cells in collagen can be manipulated with retinoids and steroids to
      resemble histological features of the proliferative and secretory phases.

PMID- 12215340
TI  - Lack of standardization in performance of the semen analysis among laboratories
      in the United States.
AB  - OBJECTIVE: To determine the level of standardization in performance of the semen
      analysis among clinical laboratories in the United States. DESIGN: A survey was
      mailed to laboratories requesting information about the laboratory and
      performance of the semen analysis. Responses were received from 536 laboratories.
      SETTING: Clinical laboratories enrolled in the American Association of
      Bioanalysts Andrology Proficiency Testing Program. PATIENT(S): None.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Agreement among laboratories.
      RESULT(S): Sixty-one percent of respondent laboratories were part of an assisted
      reproductive technology program. The laboratories perform less than 50 (53%),
      less than 10 (25%), or less than 5 (16%) andrology laboratory procedures per
      month. The laboratories routinely report sperm count (94% of laboratories),
      motility (95%), morphology (85%) and forward progression (69%), and semen volume
      (96%) as part of the semen analysis. Only 64% of laboratories routinely report
      abstinence, and 60% of laboratories indicate the criteria used for sperm
      morphology on the report form. The most common lower limits of normality for
      sperm count and motility were >20 x 10(6)/mL (77% of laboratories) and >50% (59%
      of laboratories), respectively. Few laboratories performed quality control for
      sperm counts (29%), motility (41%), and morphology (41%). CONCLUSION(S): These
      data indicate a significant lack of standardization in the performance and
      reporting of semen analyses among laboratories in the United States.

PMID- 12215341
TI  - Focused ultrasound ablation of the epididymis with use of thermal measurements in
      a canine model.
AB  - OBJECTIVE: To explore the epididymis as an alternative anatomical target to the
      vas deferens for noninvasive male sterilization using therapeutic focused
      ultrasound. DESIGN: Controlled preclinical study. SETTING: Canine animal model in
      an academic research environment. PATIENT(S): Four healthy male mongrel dogs (30
      35 kg). INTERVENTION(S): A transducer mounted on a plastic clip delivered
      ultrasound energy to the canine epididymis. Thermocouples placed transcutaneously
      into the epididymis, intradermally, and on the skin surface recorded temperatures
      during ablation with a wide range of acoustic powers and sonication times
      (control, 3 W/120 s, 5 W/90 s, 7 W/60 s). MAIN OUTCOME MEASURE(S): Thermocouple
      temperature measurements determined the optimal range of ablation parameters that
      produced successful thermal occlusion of the epididymis without adverse effects
      (e.g., skin burns, testicular injury). RESULT(S): A large "therapeutic window"
      was determined (power = 3-7 W, time = 20-120 seconds) over which noninvasive
      thermal occlusion of the epididymis can be achieved. Thermal occlusion rates were
      higher, and complications lower, than found previously with vas deferens
      ablation. CONCLUSION(S): The epididymis represents a larger and easier target
      than the vas deferens for performing noninvasive male sterilization using focused
      ultrasound. Long-term azoospermia studies will be necessary to confirm permanent
      sterilization with this technique.

PMID- 12215342
TI  - Reliability of clinicians versus radiologists for detecting abnormalities on
      hysterosalpingogram films.
AB  - OBJECTIVE: To evaluate the consistency of the identification of abnormal findings
      on hysterosalpingogram (HSG) and compare the reliability of clinicians to that of
      radiologists. DESIGN: Evaluation of reliability of diagnostic test. PATIENT(S):
      Women undergoing evaluation for infertility.INTEVENTION(S): Retrospective review
      of 50 HSG films by three reproductive endocrinologists and three radiologists.
      Each film was reread 30 days later in a blinded fashion. MAIN OUTCOME MEASURE(S):
      The consistency of each individual reader, the reliability of detecting specific
      abnormalities, and the consistency of clinicians compared with radiologists was
      evaluated with a kappa (K) statistic and interclass correlation coefficient
      (ICC). RESULT(S): Average intrareader reliability was high for the detection of
      normal uterus, normal tubes, and tubal obstruction and low for the detection of
      hydrosalpinx, uterine adhesions, and pelvic adhesions. Inter-reader reliability
      was high in the detection of normal uterine contour, normal tubal patency, and
      uterine filling defect and lower for the detection of a hydrosalpinx. The
      reliability of detecting pelvic adhesion or salpingitis isthmica nodosa was poor.
      CONCLUSION(S): Intrareader reliability was generally good, especially for the
      detection of normal findings. Agreement among different readers is lower in
      detecting rare outcomes such as hydrosalpinx and pelvic adhesion and salpingitis
      isthmica nodosa. Clinicians more reliably diagnose hydrosalpinx and tubal
      obstruction, while radiologists more reliably detect the more subtle findings of
      salpingitis isthmica nodosa or uterine adhesions.

PMID- 12215343
TI  - Use of a modified intracytoplasmic sperm injection technique to overcome sperm
      borne and oocyte-borne oocyte activation failures.
AB  - OBJECTIVE: To examine whether sperm-borne and oocyte-borne oocyte activation
      failures can be overcome by mechanical means that entail modifying the ICSI
      technique. DESIGN: Case report series. SETTING: Private clinics. PATIENT(S): Six
      infertile couples undergoing ICSI. INTERVENTION(S): Standard ICSI and modified
      ICSI based on mechanical manipulation that facilitated entry of calcium into the
      oocyte. MAIN OUTCOME MEASURE(S): Fertilization rate and pregnancy outcome.
      RESULT(S): In three cases of sperm-borne and three cases of oocyte-borne oocyte
      activation deficiencies, the modified ICSI technique enabled normal fertilization
      and development of embryos with good morphology. In terms of fertilization, the
      efficacy of modified ICSI was similar to use of a calcium ionophore, without
      producing extensive embryo fragmentation during postfertilization development.
      Term pregnancies resulting in the birth of normal children were achieved with the
      modified ICSI technique in five cases. CONCLUSION(S): Sperm-borne and oocyte
      borne oocyte activation failures can be overcome by modifying the ICSI technique.
      The modification obviates the need to use insufficiently tested and potentially
      harmful drugs.

PMID- 12215344
TI  - Culdoscopy using an optical cannula.
AB  - OBJECTIVE: To describe a technique for inserting an endoscope through the
      posterior vaginal fornix under direct vision using an optical cannula. DESIGN:
      Prospective case study. SETTING: University Department of Obstetrics &
      Gynecology. PATIENT(S): Patients with infertility referred for investigation in
      secondary care. INTERVENTION(S): Insertion of culdoscope using an optical
      cannula. MAIN OUTCOME MEASURE(S): Successful introduction of the culdoscope.
      RESULT(S): Sixteen of 20 patients had successful introduction of the optical
      cannula. There were no reported complications. CONCLUSION(S): Insertion of a
      culdoscope into the cul-de-sac can be done under visual control and this may
      reduce the risks of complications associated with blind insertion using a
      modified Veress needle.

PMID- 12215345
TI  - Comparison of hysteroscopic and hysterectomy findings for assessing the
      diagnostic accuracy of office hysteroscopy.
AB  - OBJECTIVE: To assess the diagnostic accuracy of office hysteroscopy by comparing
      the hysteroscopic findings with the histologic findings on the hysterectomy
      specimens. DESIGN: Retrospective clinical study. SETTING: University-affiliated
      hospital. PATIENT(S): Review of the hospital records of 443 patients who
      underwent office hysteroscopy and, within 2 months, hysterectomy.
      INTERVENTION(S): We compared the hysteroscopic findings (including targeted
      biopsies) with the histologic findings that were obtained after hysterectomy. The
      results of this study were then compared with those of a previous study in which
      we examined the diagnostic accuracy of dilatation and curettage (D&C). MAIN
      OUTCOME MEASURE(S): We evaluated the diagnostic accuracy of office hysteroscopy.
      RESULT(S): When compared with the histologic diagnosis of the uterus, the
      hysteroscopic findings showed a diagnostic sensitivity of 98%, a specificity of
      95%, a positive predictive value (PPV) of 96%, and a negative predictive value
      (NPV) of 98%. Hysteroscopy was found to have a greater diagnostic accuracy than
      D&C: the sensitivity and the NPV of the two diagnostic procedures were
      statistically different. CONCLUSION(S): Office hysteroscopy is confirmed as a
      powerful diagnostic tool, but targeted biopsies, performed with a small diameter
      operative hysteroscope, must be performed in cases of suspect endometrium to
      confirm the image-based diagnosis.

PMID- 12215346
TI  - Unusual growth of a myoma during pregnancy.

PMID- 12215347
TI  - Absence of sperm sex chromosome aneuploidies in an X0/XYY man.
AB  - OBJECTIVE: To determine appropriate genetic counseling of patients with a mosaic
      karyotype who wished to undergo assisted reproduction technology. DESIGN: Case
      report. SETTING: A tertiary center for assisted reproduction technology.
      PATIENT(S): A male with a mosaic karyotype X0/XYY. INTERVENTION(S): Analysis of
      ejaculated spermatozoa by using fluorescence in situ hybridisation with probes
      directed against chromosomes X, Y, and 18. MAIN OUTCOME MEASURE(S): Degree of sex
      chromosome aneuploidies in spermatozoa. RESULT(S): Levels of sex chromosome
      aneuploidies in spermatozoa were normal. On the basis of these findings, the
      couple proceeded to assisted reproduction technology without preimplantation
      genetic diagnosis and conceived a healthy male baby. CONCLUSION(S): Sex
      chromosome mosaicism in men does not necessarily lead to high levels of abnormal
      spermatozoa. Sex chromosome aneuploidies may be eliminated in the testes through
      the selective degeneration of abnormal spermatogenic cells.

PMID- 12215348
TI  - Fertility after conservative treatment of placenta accreta.
AB  - OBJECTIVE: To report a pregnancy with vaginal delivery after a preceding
      pregnancy complicated by placenta accreta that was managed conservatively.
      DESIGN: Case report. SETTING: University medical center. PATIENT(S): A patient
      with placenta accreta that was managed conservatively. INTERVENTION(S): The
      placenta was left in situ and both uterine arteries were embolized. MAIN OUTCOME
      MEASURE(S): Preservation of reproductive capacity. RESULT(S): The patient had a
      term pregnancy with uncomplicated vaginal delivery. CONCLUSION(S): Pregnancy is
      possible after conservative treatment of placenta accreta. This treatment should
      be considered in the appropriate circumstances to preserve reproductive capacity.

PMID- 12215349
TI  - Comparison of metaphase II oocytes after stimulation with recombinant follicle
      stimulating hormone and urinary follicle-stimulating hormone in a pituitary down
      regulation regimen.

PMID- 12215350
TI  - In vitro fertilization is a risk factor for vasa previa.

PMID- 12215351
TI  - Ultrastructure of follicles after vitrification of mouse ovarian tissue.

PMID- 12215352
TI  - Preoperative and intraoperative factors that predict difficult testicular sperm
      retrieval in patients with nonobstructive azoospermia.

PMID- 12215353
TI  - Comparison of various sedation regimens for transvaginal oocyte retrieval.

PMID- 12215354
TI  - A reanalysis of a reanalysis! The path to enlightenment.

PMID- 12215356
TI  - A reanalysis of a reanalysis! The path to enlightenment.

PMID- 12215357
TI  - Advisory counsel survey and the role of IUI.

PMID- 12215359
TI  - Standard IVF and ICSI--how much do the conclusions differ?

PMID- 12215361
TI  - Standard IVF and ICSI--how much do the conclusions differ?

PMID- 12215362
TI  - Clomid versus metformin for ovulation induction--let's not have any "hanging
      chads"!

PMID- 12215364
TI  - Clomid versus metformin for ovulation induction--let's not have any "hanging
      chads"!

PMID- 12215365
TI  - A new method for sperm perfusion with a blocking device?

PMID- 12215368
TI  - Transgenic studies of alpha(1)-adrenergic receptor subtype function.
AB  - Mice with altered alpha(1)-adrenergic receptor (AR) genes have become important
      tools in elucidating the subtype-specific functions of the three alpha(1)-AR
      subtypes because of the lack of sufficiently subtype-selective pharmacological
      agents. Mice with a deletion (knockout, KO) or an overexpression (transgenic, TG)
      of the alpha(1A)-, alpha(1B)-, or alpha(1D)-AR subtypes have been generated. The
      alpha(1)-ARs are the principal mediators of the hypertensive response to alpha(1)
      agonists in the cardiovascular system. Studies with these mice indicate that
      alpha(1A)-AR and alpha(1B)-AR subtypes play an important role in cardiac
      development and/or function as well as in blood pressure (BP) response to
      alpha(1)-agonists via vasoconstriction. The alpha(1B)- and alpha(1D)-subtypes
      also appear to be involved in central nervous system (CNS) processes such as
      nociceptive responses, modulation of memory consolidation and working memory. The
      ability to study subtype-specific functions in different mouse strains by
      altering the same alpha(1)-AR in different ways strengthens the conclusions drawn
      from these studies. Although these genetic approaches have limitations, they have
      significantly increased our understanding of the functions of alpha(1)-AR
      subtypes.

PMID- 12215369
TI  - Cellular localization of cannabinoid receptors and activated G-proteins in rat
      anterior cingulate cortex.
AB  - Cannabinoid receptors are found in moderate density throughout the cerebral
      cortex. The anterior cingulate cortex (ACC) is of particular interest due its
      high level of cannabinoid receptors and role in behaviors known to be modulated
      by cannabinoids. These studies were conducted to determine the cellular
      localization of cannabinoid receptors and to compare the level of cannabinoid
      receptor binding with receptor-mediated G-protein activity in the rat ACC. Either
      ibotenic acid or undercut lesions were made in ACC, and brains were processed for
      [3H]WIN 55,212-2 and WIN 55,212-2-stimulated [35S]GTPgammaS autoradiography. Both
      cannabinoid receptors and receptor-activated G-proteins were highest in laminae I
      and VI of ACC in control tissue. Although similar levels of receptor binding were
      found in these laminae, significantly higher levels of receptor-activated G
      proteins were found in lamina VI. Ibotenic acid lesions that destroyed ACC
      neurons decreased [3H]WIN 55,212-2 binding by 60-70% and eliminated WIN 55,212-2
      stimulated [35S]GTPgammaS binding. In contrast, deafferentation of the ACC with
      undercut lesions had no significant effect on cannabinoid receptor binding or G
      protein activation. These results indicate that cannabinoid receptors in laminae
      I and VI of the ACC are located on somatodendritic elements or axons intrinsic to
      the ACC. In addition, differences in the relative levels of cannabinoid binding
      sites and activated G-proteins between cortical laminae indicate that the
      efficiency of cannabinoid receptors for G-protein activation may vary within a
      specific brain region.

PMID- 12215370
TI  - Inhibition of vesicular uptake of monoamines by hyperforin.
AB  - Hyperforin is the major active ingredient of Hypericum perforatum (St John's
      Wort), a traditional antidepressant medication. This study evaluated its
      inhibitory effects on the synaptic uptake of monoamines in rat forebrain
      homogenates, comparing the nature of the inhibition at synaptic and vesicular
      monoamine transporters. A hyperforin-rich extract inhibited with equal potencies
      the sodium-dependent uptake of the monoamine neurotransmitters serotonin [5-HT],
      dopamine [DA] and norepinephrine [NE] into rat brain synaptosomes. Hyperforin
      inhibited the uptake of all three monoamines noncompetitively, in marked contrast
      with the competitive inhibition exerted by fluoxetine, GBR12909 or desipramine on
      the uptake of these monoamines. Hyperforin had no inhibitory effect on the
      binding of [3H]paroxetine, [3H]GBR12935 and [3H]nisoxetine to membrane
      presynaptic transporters for 5-HT, DA and NE, respectively. The apparent
      presynaptic inhibition of monoamine uptake could reflect a "reserpine-like
      mechanism" by which hyperforin induced release of neurotransmitters from synaptic
      vesicles into the cytoplasm. Thus, we assessed the effects of hyperforin on the
      vesicular monoamine transporter. Hyperforin inhibited with equal potencies the
      uptake of the three tritiated monoamines to rat brain synaptic vesicles.
      Similarly to the synaptosomal uptake, the vesicular uptake was also
      noncompetitively inhibited by hyperforin. Notably, hyperforin did not affect the
      direct binding on [3H]dihydrotetrabenazine, a selective vesicular monoamine
      transporter ligand, to rat forebrain membranes. Our results support the notion
      that hyperforin interferes with the storage of monoamines in synaptic vesicles,
      rather than being a selective inhibitor of either synaptic membrane or vesicular
      monoamine transporters.

PMID- 12215371
TI  - Role of membrane potential in vasomotion of isolated pressurized rat arteries.
AB  - Vasomotion, the phenomenon of vessel diameter oscillation, regulates blood flow
      and resistance. The main parameters implicated in vasomotion are particularly the
      membrane potential and the cytosolic free calcium in smooth muscle cells. In this
      study, these parameters were measured in rat perfused-pressurized mesenteric
      artery segments. The application of norepinephrine (NE) caused rhythmic diameter
      contractions and membrane potential oscillations (amplitude; 5.3 +/- 0.3 mV,
      frequency; 0.09 +/- 0.01 Hz). Verapamil (1 microM) abolished this vasomotion.
      During vasomotion, 10(-5) M ouabain (Na(+)-K(+) ATPase inhibitor) decreased the
      amplitude of the electrical oscillations but not their frequency (amplitude; 3.7
      +/- 0.3 mV, frequency; 0.08 +/- 0.002 Hz). Although a high concentration of
      ouabain (10(-3) M) (which exhibits non-specific effects) abolished both
      electrical membrane potential oscillations and vasomotion, we conclude that the
      Na+-K+ ATPase could not be implicated in the generation of the membrane potential
      oscillations. We conclude that in rat perfused-pressurized mesenteric artery, the
      slow wave membrane type of potential oscillation by rhythmically gating voltage
      dependent calcium channels, is responsible for the oscillation of intracellular
      calcium and thus vasomotion.

PMID- 12215372
TI  - Myocardial protection of MCI-186 in rabbit ischemia-reperfusion.
AB  - We observed that 3-methyl-1-1phenyl-2-pyrazolin-5-one (MCI-186), a newly
      developed free radical scavenger, attenuated necrosis in the in vivo rabbit
      hearts upon reperfusion after prolonged ischemia. In rabbits undergoing 1 hour
      ligation of the anterior ventricular coronary artery, a single bolus injection of
      MCI-186 (1.5 mg/kg) was introduced into the post-ischemic heart immediately
      before 4 hour reperfusion. Compared to negligible necrosis in sham-operated
      control animals and 33.81 +/- 13.50% necrosis in the area at risk for the saline
      control group (n = 8), the MCI-186 - treated group (n = 8) had a necrosis of
      13.27 +/- 4.60% (p < 0.05 vs saline control group). The pressure-rate index had a
      slight decrease in MCI-186 treated group compared to the control group (p >
      0.05). However, the blood levels of malondialdehyde (MDA) in MCI-186 treated
      group (2.08 +/- 0.23 microM) was significantly smaller than that of 2.65 +/- 0.31
      microM in control animals (p < 0.01), while sham control had an average MDA level
      of 1.91 +/- 0.40 microM, with p > 0.05 relative to that in the MCI-186 treated
      group. These data support our contention that MCI-186 reduces reperfusion injury
      in perfused hearts with prolonged ischemia and the mechanism for the in vivo
      efficacy of MCI-186 is predominantly related to its antioxidant activities.

PMID- 12215373
TI  - Regulation of the expression of protein kinase C isoenzymes in rat ventral
      prostate: effects of age, castration and flutamide treatment.
AB  - Protein kinase C (PKC) isoenzymes are involved in cell function, growth,
      apoptosis and neoplastic transformation in the prostate gland. We detected by
      means of Western blot the expression of the classical alpha and beta1, the novel
      epsilon and the atypical zeta isoforms of PKC in ventral prostates from rats with
      different extents of plasma testosterone levels and/or androgen imprinting on the
      gland. The expression of the four isoforms decreased in 5-day castrated rats
      showing apoptotical regression of the gland and a drastic reduction of
      circulating testosterone. However, the expression of PKC isoenzymes (alpha,
      beta1, epsilon ) increased in prostates from pubertal (35-days old) rats that are
      characterized by relatively low but extremely bioactive testosterone plasma
      levels. Treatment of adult rats for 14 days with flutamide (daily s.c. injection
      of 15 mg/Kg B.W.) resulted in increased expression of the four isoenzymes; it
      occurred in the presence of increased (normal rats) or drastically reduced (rats
      castrated after 9 days of flutamide administration) levels of plasma testosterone
      conceivably through a direct effect of this nonsteroidal antiandrogen on prostate
      cells. Measurements of PKC(alpha) activity were in agreement with the
      observations on protein expression and showed that flutamide (that is extensively
      used in the treatment of advanced prostate cancer) elicits some impairment in the
      mechanisms of translocation of this isoform from the cytosol to the membrane.
      Thus, in addition to the possibility of direct effects of flutamide upon the rat
      prostate, we present evidence that the levels of circulating androgens and/or
      their bioactivity in the gland regulate the expression of various important PKC
      isoforms.

PMID- 12215374
TI  - Paeoniae Radix, a Chinese herbal extract, inhibit hepatoma cells growth by
      inducing apoptosis in a p53 independent pathway.
AB  - Paeoniae Radix (PR) is the root of traditional Chinese Herb named Paeonia
      lactiflora Pallas, which is commonly used to treat liver diseases in China for
      centuries. Several earlier studies have indicated that PR has anticancer growth
      activities, however the mechanism underlying these activities was unclear and
      remained to be elucidated. In this study, we evaluated the molecular mechanism of
      the effect of PR on human hepatoma cell lines, HepG2 and Hep3B. Our results
      showed that the water-extract of Paeoniae Radix (PRE) had inhibitory effect on
      the growth of both HepG2 and Hep3B cell lines. The induction of internucleosomal
      DNA fragmentation and chromatin condensation appearance, and accumulation of sub
      G1 phase of cell cycle profile in PRE treated hepatoma cells evidenced that the
      cytotoxicity of PRE to the hepatoma cells is through activation of the cell death
      program, apoptosis. The activation of apoptosis by PRE is independent of the p53
      pathway as Hep3B cell is p53-deficient. In addition, the differential gene
      expression of PRE treated HepG2 was examined by cDNA microarray technology and RT
      PCR analysis. We found that the gene expression of BNIP3 was up-regulated while
      ZK1, RAD23B, and HSPD1 were down-regulated during early apoptosis of the hepatoma
      cell mediated by PRE. The elucidation of the drug targets of PR on inhibition of
      tumor cells growth should enable further development of PR for liver cancer
      therapy.

PMID- 12215375
TI  - 5-HT7 receptors are involved in mediating 5-HT-induced activation of rat primary
      afferent neurons.
AB  - The purpose of this study was to determine whether the 5-hydroxytryptamine7 (5
      HT7) receptor is expressed by nociceptor-like neurons in the rat PNS and whether
      5-HT activates these nociceptors via the 5-HT7 receptor subtype. Using a
      polyclonal antibody and the method of immunofluorescence staining, we
      demonstrated that the 5-HT7 receptor appears predominately on "nociceptor-like"
      neurons of the rat lumbar dorsal root ganglia. Using immunocytochemical methods,
      we showed that the immunoreactivity of the 5-HT7 receptor antibody complex is
      localized in the superficial layers of the spinal cord dorsal horn, which
      corresponds with laminae I, IIouter and IIinner. Furthermore, we demonstrated
      that noxious stimulation produced by knee injection of 5-HT or a 5-HT7 agonist
      dose-dependently increases c-Fos production of the rat spinal cord dorsal horn.
      This effect was significantly inhibited by the preinjection of a 5-HT7
      antagonist. We conclude that the 5-HT7 receptor is expressed by rat primary
      afferent nociceptors which terminate in the superficial layers of the spinal cord
      dorsal horn and that the 5-HT7 receptor subtype is involved in nociceptor
      activation by 5-HT.

PMID- 12215376
TI  - Effects of water deprivation for 72 hours on the pharmacokinetics of a new
      carbapenem, DA-1131, in rats.
AB  - Hormonal, physiological, and biochemical changes occurring in dehydrated patients
      could alter the pharmacokinetics of the drugs; therefore, the pharmacokinetics of
      DA-1131, a new carbapenem antibiotic, were investigated after 1-min intravenous
      administration of the drug at 50 mg/kg to control and 72-hr water-deprived rats.
      The impaired kidney and liver functions were observed in water-deprived rats on
      the basis of tissue microscopic examination. After intravenous infusion of the
      drug to water-deprived rats, the plasma concentrations of DA-1131 were higher and
      this resulted in a significantly greater total area under the plasma
      concentration-time curve from time zero to time infinity than those in control
      rats (4520 versus 3760 microg min/ml). This could be due to significantly slower
      total body clearance (CL) of DA-1131 in water-deprived rats (9.81 versus 14.1
      ml/min/kg). The significantly slower CL of DA-1131 in water-deprived rats was due
      to significant decrease in both renal clearance (2.87 versus 5.13 ml/min/kg
      because of a significant decrease in 8-hr urinary excretion of unchanged DA-1131
      [28.4 versus 39.9% of the intravenous dose] due to impaired kidney function) and
      nonrenal clearance (6.82 versus 8.66 ml/min/kg because of a significant decrease
      in the metabolism of DA-1131 in the kidney, as proved by the significant decrease
      in total renal DHP-I enzyme activity [1900 versus 2130 mU/each kidney]) in water
      deprived rats. Water-deprivation did not alter the affinity of rat tissues to DA
      1131.

PMID- 12215377
TI  - Ischemic preconditioning changes the pattern of coronary reactive hyperemia
      regardless of mitochondrial ATP-sensitive K(+) channel blockade.
AB  - Ischemic preconditioning increases the velocity of vasodilatation and reduces the
      total hyperemic flow (THF) of a subsequent coronary reactive hyperemia (CRH). The
      increase in the velocity of vasodilatation has been shown to depend on an up
      regulation of the endothelial release of nitric oxide, while the reduction of THF
      is attributed to an adenosine A(1) receptor-mediated mechanism. We investigated
      whether the changes in CRH induced by preconditioning ischemia (PI) can still be
      obtained after blockade of mitochondrial ATP-sensitive K(+) channels by sodium 5
      hydroxydecanoate (5-HD), and whether the blockade per se affects the pattern of
      CRH. In anesthetized goats, flow was recorded from the left circumflex coronary
      artery (LCCA). CRH was obtained with the occlusion of LCCA for 15 s. PI was
      obtained by 2 cycles of 2.5 min of LCCA occlusion with a 5 min interval of
      reperfusion between the two occlusions. CRH was studied before and after i.v.
      administration of 5-HD (20 mg/kg), as well as in the presence of 5-HD after PI.
      Following 5-HD, the pattern of CRH remained unchanged. After 5-HD and PI,
      velocity of vasodilatation and total hyperemic flow of CRH showed the same
      changes as in previous studies after PI alone. It was concluded that the blockade
      of mitochondrial ATP-sensitive K(+) channels, which is reported to prevent
      myocardial protection, does not affect CRH and does not prevent PI from
      increasing the velocity of vasodilatation and reducing THF. These results
      demonstrate that the changes induced in CRH by preconditioning are independent of
      the opening of the mitochondrial ATP-sensitive K(+) channels.

PMID- 12215378
TI  - Effect of piperine, the active ingredient of black pepper, on intestinal
      secretion in mice.
AB  - We have investigated the effect piperine on castor oil-stimulated fluid
      accumulation in the mouse small intestine. Piperine (2.5-20 mg/kg, i.p.) dose
      dependently reduced castor oil-induced intestinal fluid accumulation. The
      inhibitory effect of piperine (10 mg/kg i.p.) was strongly attenuated in
      capsaicin (75 mg/kg in total, s.c.)-treated mice but it was not modified by the
      vanilloid receptor antagonist capsazepine (30 mg/kg i.p.). Pretreatment of mice
      with hexamethonium (1 mg/kg i.p.), naloxone (2 mg/kg i.p.), yohimbine (1 mg/kg
      i.p.) or the cannabinoid CB(1) receptor antagonist SR141716A (0.3 mg/kg i.p.) did
      not modify the inhibitory effect of piperine (10 mg/kg i.p.). These results
      suggest that piperine reduces castor oil-induced fluid secretion with a mechanism
      involving capsaicin-sensitive neurons, but not capsazepine-sensitive vanilloid
      receptors.

PMID- 12215379
TI  - Human thrombocytes are able to induce a myocardial dysfunction in the ischemic
      and reperfused guinea pig heart mediated by free radicals-role of the GPIIb/IIIa
      blocker tirofiban.
AB  - In recent studies, we could demonstrate a myocardial dysfunction induced by
      homologous platelets in ischemic and reperfused guinea pig hearts. Aim of the
      current study was to find out whether or not this is a phenomenon specific for
      platelets isolated from guinea pigs and to further examine the mechanisms of a
      possible cardiodepressive effect of human platelets. Isolated guinea pig hearts
      were exposed to a 30 min low-flow ischemia (1 ml/min) and reperfused. Human
      thrombocytes were administered as bolus (20.000 thrombocytes/microl perfusion
      buffer) in the 15(th) min of ischemia or in the 1(st) or 5(th) min of reperfusion
      in the presence of thrombin. Recovery of external heart work (REHW) and
      intracoronary platelet retention (RET) were quantified in percent. In additional
      experiments, the GPIIb/IIIa-blocker tirofiban (10 microg/ml perfusion buffer) or
      the radical scavenger superoxide dismutase (SOD-10 U/ml perfusion buffer) were
      added. Platelet application in the absence of tirofiban, either during ischemia
      (REHW 75.4 +/- 4%, RET 22.2 +/- 2%) or the 1st min (REHW 71.6 +/- 1%, RET 31.2 +/
      2%) or the 5th min of reperfusion (REHW 63.2 +/- 4%, RET 40.5 +/- 1%) led to a
      significant reduction of REHW and a significant increase of RET. The
      coapplication of tirofiban, on the other hand, prevented RET at all three times
      of platelet application (1.1 +/- 1.7%, 0% or 2.1 +/- 1.2%, respectively). An
      improvement of REHW, however, could only be noticed during ischemia (89 +/- 2%),
      whereas coapplication of tirofiban in early (72.9 +/- 3%) or in late reperfusion
      (74.6 +/- 2%) did not lead to a significant increase of REHW. Coapplication of
      SOD, on the other hand, significantly improved REHW in early (88.1 +/- 1) or late
      (95.9 +/- 1) reperfusion but not during ischemia (83.5 +/- 2). Corresponding to
      REHW, RET was changed significantly by coapplication of SOD during early (1 +/-
      2%) or late (0%) reperfusion but not during ischemia (21.1 +/- 4%). We conclude
      that human thrombocytes are able to induce a myocardial dysfunction in ischemic
      and reperfused guinea pig hearts mediated by reactive oxygen species and
      independent of intracoronary platelet adhesion.

PMID- 12215380
TI  - Establishment of the superoxide production assay with human monocytic cell line,
      U937, for the evaluation of Syk kinase inhibitors.
AB  - Protein tyrosine kinase Syk is known to play critical roles in the signal
      transduction from receptors for Fc portion of immunoglobulins (FcRs) and B cell
      receptor complex (BCR). Its importance was well studied in Fc epsilon RI-induced
      activation of mast cells; therefore, Syk inhibitors are expected to have anti
      allergic effects and to be novel therapy for allergic diseases, such as asthma,
      allergic rhinitis and atopic dermatitis. We previously developed an enzyme assay
      of recombinant human Syk kinase for the high throughput screening. In order to
      evaluate the Syk kinase inhibitors in a human cell system, we have developed an
      assay with human monocytic cell line, U937, to monitor FcgammaRI-mediated
      superoxide production. We treated cells with IFN-gamma to enhance the expression
      of FcgammaRI and to obtain enough production of superoxide. Engagement of
      FcgammaRI stimulated superoxide production, which was accompanied with Syk
      phosphorylation. PMA, an activator of protein kinase C, also evoked superoxide
      production, but Syk was not phosphorylated. Moreover, the treatment of cells with
      antisense oligonucleotide against syk attenuated Syk protein expression and
      suppressed superoxide production induced by FcgammaRI-engagement, but not by PMA.
      These results confirm that Syk is involved in the signal transduction from
      FcgammaRI upstream of PKC in U937 cells and we can evaluate the efficacy and the
      selectivity of Syk inhibitors with this assay system.

PMID- 12215381
TI  - Large-scale generation of mature monocyte-derived dendritic cells for clinical
      application in cell factories.
AB  - Dendritic cells (DC) are increasingly used for the immunotherapy of cancer. Both
      the induction of tumor-specific T cells and some clinical regressions have been
      observed in early phase I/II trials by using either DC isolated from blood, DC
      generated from CD34+ precursors ex vivo, and most frequently, by employing
      monocyte-derived DC. As DC vaccination is now awaiting phase II/III trials with
      larger patient collectives, it becomes increasingly important to overcome prior
      limitations such as the repetitive, labor-intensive generation of DC in a large
      number of open culture vessels. We describe here as a result of several years of
      optimization, in detail, a procedure that uses the so-called Nunc cell factories
      to process a whole apheresis product, labor- and cost-effectively in a quasi
      closed system to reproducibly generate (by using GM-CSF+IL-4 followed by a
      maturation cocktail composed of IL-1beta+IL-6+TNF-alpha +PGE(2)) large numbers
      (8.32+/-3.8% of input peripheral blood mononuclear cells (PBMC)) of mature (>85%
      CD83+), monocyte-derived DC that can be successfully cryopreserved. Our report is
      based on the processing of >100 aphereses including 52 unselected aphereses in
      advanced melanoma patients. This allows us also to suggest meaningful quality and
      validation criteria. The DC generation method appears particularly promising as
      respective DC vaccination proved to be immunogenic in cancer patients and cell
      factories can readily be converted to a fully closed system by using appropriate
      valves, tubings, and bags.

PMID- 12215382
TI  - A skeletal muscle troponin T specific ELISA based on the use of an antibody
      against the soluble troponin T (16-31) fragment.
AB  - Proteolytic degradation of muscle, which occurs post-mortem as part of the meat
      ageing process, results in the production of protein fragments. In beef,
      degradation of skeletal muscle troponin T (TnT) results in the generation of a 16
      residue long peptide (TnT (16-31)), identified in trichloroacetic acid (TCA)
      soluble extracts. We report the development of a competitive enzyme-linked
      immunosorbent assay (ELISA) for the quantification of TnT (16-31), using
      polyclonal antibodies raised against synthetic TnT (16-31). The ELISA procedure
      is based on inhibition of binding of the antibodies to immobilised TnT (16-31) by
      TnT (16-31) present in solution. Its useful range is 30 pmol to 2 nmol TnT (16
      31)/ml. Quantification of TnT (16-31) in TCA muscle extracts showed that its
      concentration was enhanced with ageing. Moreover, a correlation between TnT (16
      31) levels and meat tenderness was observed. The ELISA developed herein may prove
      advantageous for future use at the research and industrial level.

PMID- 12215383
TI  - A hemolytic assay for the estimation of functional mannose-binding lectin levels
      in human serum.
AB  - A simple assay was developed to estimate functional mannose-binding lectin (MBL)
      levels in serum based on the principle of yeast-induced bystander lysis of
      chicken erythrocytes (ChE). The assay is sensitive to inhibition by ethylene
      glycol bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) (which
      allows alternative pathway activation), ethylene diamine tetraacetic acid (EDTA),
      mannose, N-acetylglucosamine and C1 esterase inhibitor (C1-INH), whereas it was
      not inhibited by galactose. A high-titer human anti-mannan antibody-containing
      serum with 0.06 microg MBL/ml gave a functional signal corresponding to 0.12
      microg equivalents MBL/ml, indicating that anti-mannan antibodies are poorly
      hemolytic in the assay. The assay is well suited for the large-scale testing of
      patient samples for a functional MBL pathway of complement activation.

PMID- 12215384
TI  - A new statistical method for quantitative analyses: application to the precise
      quantification of T cell receptor repertoires.
AB  - In experimental immunology, a situation quite commonly arises in which there are
      a large number of potential events but the probability of any individual event is
      small and one wishes to measure the number of events which actually occur. We
      present a new general statistical method, denoted Continuous Poisson Method
      (COPOM), for estimating the number of events underlying a quantitative
      measurement. This situation is well illustrated in the case of quantitative
      analyses of the immune receptor repertoire in a diverse population of cells. We
      show that repetition of T cell receptors (TCRs) complementarity determining
      region 3 (CDR3) length measurements by Immunoscope, on independent samples
      containing the similar numbers of cells prepared from splenocytes, results in
      variable profiles. When analyzed by COPOM, this variability provides direct
      quantification of the lymphocytes expressing any antigen receptor with a given V,
      J and CDR3 length inside the cell population. Using COPOM, a single dilution was
      sufficient to cover events over a 100-fold variation in frequency and the
      sensitivity of the assay was such that a single cell inside a pool of 5 x 10(4)
      lymphocytes could be quantified. A comparison of the frequency of splenocytes
      using either Vbeta14-Jbeta or the specific Vbeta8.3-Jbeta1.1 rearrangement,
      determined either by our or other approaches, revealed the accuracy and
      convenience of our method. This approach provides the first precise method able
      to measure the diversity of the antigen receptor repertoire inside a complex cell
      population by the use of a single straightforward technique.

PMID- 12215385
TI  - Covalent immobilization of proteins onto photoactivated polystyrene microtiter
      plates for enzyme-linked immunosorbent assay procedures.
AB  - Enhancement of the speed and sensitivity of an ELISA technique was achieved by
      doing it on a polystyrene microtiter plate preactivated by a simple photochemical
      reaction. Immobilization of Epicoccum nigrum antigen (allergenic antigen) or goat
      anti-rabbit IgG onto the photoactivated plates was found to occur in only 45 min
      with higher binding than that obtained through adsorption during the same period
      onto the untreated surface. Nearly 1.5-2-folds higher readings were obtained when
      the ELISA was carried out with the solid phase prepared on the photoactivated
      surface rather than on the untreated surface. Moreover, solid phases prepared on
      the activated surface could detect IgE (E. nigrum antibody) even at 1/50 (v/v)
      dilutions, whereas a solid phase prepared on the untreated surface failed to do
      so. Around three times higher ELISA values were obtained in the activated plate
      than the untreated plate when IgE was diluted to 1/5 (v/v). Such photoactivated
      surface could be of great importance in diagnostic tests involving the ELISA
      technique particularly to confirm false negative cases and for other immunoassays
      such as radioimmunoassay procedures.

PMID- 12215386
TI  - A flow cytometry-based assay for quantitative analysis of cellular proliferation
      and cytotoxicity in vitro.
AB  - A novel method based on flow cytometry (FCM), which can count the number of
      detected cells, has been developed for the evaluation of cellular proliferation
      and cytotoxicity in vitro. It provides a tool that directly counts cell number
      without being influenced by the metabolic state of the cells, discriminates
      target cells from effector cells in cell-mediated cytotoxicity assay, and with
      less treatment step and free radioactivity. In this paper, we have prepared the
      PG cells (a highly metastatic human lung cancer cell line) and peripheral blood
      lymphocytes (PBL) with various concentrations and ratios of concentration to
      validate the method. The results were compared with MTT (3-(4,5-dimethylthiazol-2
      yl) 2,5-diphenyl tetrazolium bromide) assay and the regression analysis results
      showed that this method worked very well. We have also used this method to
      evaluate mitogen-induced proliferation and cytotoxicity. The results indicated
      that this method might yield high sensitivity and reliability.

PMID- 12215387
TI  - Measurement of changes in mRNA for IL-5 in noninvasive scrapings of nasal
      epithelium taken from patients undergoing nasal allergen challenge.
AB  - Nasal allergen challenge of patients with allergic rhinitis results in increased
      numbers of inflammatory cells and increased production of pro-inflammatory
      cytokines including interleukin 5 (IL-5). We report a sensitive, noninvasive
      method to measure changes in the amount of mRNA for IL-5 in nasal epithelium and
      have used this method to detect alterations of IL-5 mRNA from patients undergoing
      a nasal allergen challenge. Ten grass or ragweed allergic adults were challenged
      out of season with appropriate pollen extracts at sufficient dose to give a
      rhinitis total symptom score of 5 on a scale of 12. After allergen exposure,
      symptoms were recorded hourly. At 0, 3, and 6 h after allergen exposure, secreted
      proteins were collected on filter paper strips and two superficial scrapings of
      nasal epithelium were obtained. The scrapings of epithelium were immediately
      immersed in 100 microl of RNAlater (Ambion, Austin, TX) and stored at 4 degrees C
      for up to 1 month without loss of RNA quality. Total RNA was isolated and RT-PCR
      was performed. cDNA for IL-5 was then measured by real-time fluorescence
      quantitative PCR with Pre-Developed TaqMan Assay Reagents (PE Biosystems, Foster
      City, CA). Sufficient RNA was isolated from eight subjects to measure IL-5 mRNA.
      Data were normalized for content of ribosomal RNA. The relative amount of cDNA
      for IL-5 was calculated by comparison with internal standards prepared from
      phytohemagluttinin-stimulated peripheral blood mononuclear cells. Messenger RNA
      for IL-5 was increased 8.7+/-2.7-fold at 3 h (p<0.01) and 39.5+/-20.9-fold at 6 h
      (p<0.01). Increased IL-5 mRNA levels at 6 h closely correlate with total symptom
      scores at 6 h (r=0.88; p=0.007). IL-5 protein was measured by ELISA in eluates
      from the filter papers. At 6 h, there was increased IL-5 protein (7.7+/-2.8
      ng/ml) compared with time zero (1.8+/-0.5 ng/ml) (p=0.02). The levels of IL-5
      protein did not correlate significantly with the symptoms score or with changes
      in the levels of IL-5 protein with IL-5 mRNA. These data show that changes in IL
      5 mRNA in patients with allergic rhinitis undergoing an allergen challenge
      correlate with total symptom scores better than changes in IL-5 protein eluted
      from filter paper. Furthermore, these changes can be measured quantitatively in
      very small amounts of tissue.

PMID- 12215388
TI  - Surface plasmon resonance-based competition assay to assess the sera reactivity
      of variants of humanized antibodies.
AB  - While clinical trials are the only way to evaluate the immunogenicity, in
      patients, of murine or genetically engineered humanized variants of a potentially
      therapeutic or diagnostic monoclonal antibody (MAb), ethical and logistical
      considerations of clinical trials do not permit the evaluation of variants of a
      given MAb that are generated to minimize its immunogenicity. The most promising
      variant could be identified by comparing the reactivities of the parental
      antibody (Ab) and its variants to the sera of patients containing anti-variable
      region (anti-VR) Abs to the administered parental Ab. We have developed a surface
      plasmon resonance (SPR) biosensor-based assay to monitor the binding of the sera
      anti-VR Abs to the parental Ab and the inhibition of this binding by the
      variants. SPR biosensors allow the real-time detection and monitoring of the
      binding between an immobilized protein and its soluble ligand without the need
      for prior purification and labeling of the mobile analyte. This new assay
      requires no radiolabeling, is relatively less time-consuming, and uses only small
      amounts of serum (5-20 microl of diluted serum) through a new microfluidic sample
      handling technique. To validate the assay, we have tested the relative
      reactivities of the CDR-grafted anti-carcinoma Ab, HuCC49, and its two variants,
      designated V5 and V10, to the sera of patients who were earlier administered
      radiolabeled murine CC49 in a clinical trial. A comparison of IC(50)s (the
      concentrations of the competitor Abs required for 50% inhibition of the binding
      of sera to immobilized HuCC49) showed that V5 and V10 were less reactive than
      HuCC49 to the three patients' sera tested. We have also demonstrated, for the
      first time, the specific detection and comparison of relative amounts of anti-VR
      Abs present in the sera of different patients without prior removal of anti
      murine Fc Abs and/or circulating antigen. This may facilitate the rapid
      screening, for the presence of anti-VR Abs, of the sera of patients undergoing
      clinical trials.

PMID- 12215389
TI  - A cautionary note on experimental artefacts induced by fetal calf serum in a
      viral model of pulmonary eosinophilia.
AB  - In BALB/c mice, sensitization with the attachment protein (G) of respiratory
      syncytial virus (RSV) leads to CD4(+) T cell-mediated lung eosinophilia during
      subsequent challenge with RSV. In this study, we originally intended to test
      whether activation of RSV-specific cytotoxic T cells by peptide-pulsed dendritic
      cells (DC) after G protein sensitization could prevent this eosinophilic
      response. Peptide-pulsed dendritic cells activated CTL, which could mediate
      protective immunity to RSV. However, DC vaccination aggravated, rather than
      prevented, pulmonary eosinophilia in G-sensitized mice and also enhanced weight
      loss upon RSV infection. This was accompanied by preferential pulmonary
      recruitment of CD4(+) T cells secreting IL-5. The same enhanced Th2-mediated
      eosinophilic response could be observed in mice that received unloaded dendritic
      cells and this response occurred even in the absence of prior G sensitization.
      Since both dendritic cells and RSV were grown in fetal calf serum (FCS)
      containing medium, we suspected that FCS had provoked this response. Indeed,
      neither eosinophilia nor enhanced pathology were observed in mice treated with DC
      raised in mouse serum. This observation calls for meticulous controls for
      artefacts induced by fetal calf serum particularly in mouse models of allergic
      responses of the respiratory tract.

PMID- 12215390
TI  - An ELISA avoiding interference by heterophilic antibodies in the measurement of
      components of the plasminogen activation system in blood.
AB  - Endogenous heterophilic antibodies in blood are known to interfere with two-site
      enzyme-linked immunosorbent assays (ELISAs) evoking false positive signals. In
      the present study, we describe an assay for the assessment of components of the
      plasminogen activation system (uPA, tPA and PAI-1, and their complexes) in blood
      which is not susceptible to interference by heterophilic antibodies. In the ELISA
      format, two avian (duck, chicken) antibodies are employed in the pre-analyte and
      two mammalian (rabbit, goat) antibodies in the post-analyte stage. The assay is
      compared to our earlier reported ELISA for measuring uPA, tPA and PAI-1
      components in tumor tissue extracts. Applying the so-called "nonsense formats",
      designed against non-existent components, to the NIBSC reference preparation of
      rheumatoid factor (RF), no response was found with the new assay, whereas a clear
      RF dose-dependent interfering signal was observed with the original assay
      designed for tumor tissue extracts. Analysis of tumor-tissue based international
      reference preparations (RBG EORTC 101094 and 040297), human anti-mouse antibodies
      (HAMA) containing sera, and sera from patients with rheumatoid arthritis (RA),
      also displayed no false positive signals. In conclusion, we have developed an
      ELISA that permits the determination of blood levels of components in the
      urokinase system, free from disturbance by endogenous heterophilic antibodies.

PMID- 12215391
TI  - Time-resolved fluorometric assay for the detection of endostatin in
      chromatographically separated extracts of natural peptides.
AB  - We present a heterogeneous non-competitive immunological detection assay for
      peptide and protein antigens from crude extracts of biological sources. This time
      resolved fluoroimmunoassay (TR-FIA) has been designed in a solid-phase mode using
      96-well microtiter plates. Using the rare-earth metal europium as a fluorescent
      marker, a highly sensitive, selective and efficient procedure was developed. This
      technique prevents from interferences of intrinsic protein fluorescence which is
      highly important for antigen measurement in complex matrices. The TR-FIA has been
      applied for the detection of circulating forms of the potential anti-tumor agent
      endostatin, a C-terminal fragment of collagen XVIII, and its close homolog
      collagen XV (restin) from hemofiltrate. Endostatin was detected with a limit of
      detection of 3 ng (150 fmol/well) and a broad dynamic range from 10-1000 ng/well.

PMID- 12215392
TI  - Determination of protein phosphorylation in Fc epsilon RI-activated human mast
      cells by immunoblot analysis requires protein extraction under denaturing
      conditions.
AB  - The advent of activation state antibodies has greatly facilitated studies aimed
      at understanding the intracellular signaling cascade following occupancy and/or
      aggregation of surface receptors. As part of an ongoing study investigating the
      signal transduction cascade initiated following aggregation of the high affinity
      receptor for IgE (Fc epsilon RI) in human mast cells, we observed substantial
      differences in responses monitored by these antibodies when cells were extracted
      either under nonreducing or reducing conditions. This was true even in the
      presence of high concentrations of protease inhibitors. Although the activation
      of some proteins such as those of the MAP kinase pathway appeared to be
      unaffected by the extraction conditions, other signals, including overall
      tyrosine phosphorylation and activation of phospholipase Cgamma(1), were
      substantially different. This was due to the significant proteolysis in samples
      extracted under nondenaturing conditions. When the signaling proteins were
      extracted rapidly under denaturing conditions, however, there was little evidence
      of proteolysis of the signaling proteins with a resulting improved recovery of
      signal. Thus, accurate determination of signaling events utilizing activation
      state-specific antibodies in human mast cells requires protein extraction under
      denaturing conditions. The data presented in this report would be applicable to
      other cell types where high concentrations of proteases are present.

PMID- 12215394
TI  - Abstracts of EUROTOX 2002, 15-18 September 2002. Budapest, Hungary.

PMID- 12215393
TI  - Efficient generation of monoclonal antibodies for specific protein domains using
      recombinant immunoglobulin fusion proteins: pitfalls and solutions.
AB  - Monoclonal antibody production (mAb) first requires the availability of large
      amounts of pure immunogen for animal immunisation and fusion screening
      procedures. To overcome this obstacle, we have developed a simple method for
      rapid generation of pure antigen by generation of recombinant protein containing
      the antigen of interest fused to the hinge and Fc domains of human immunoglobulin
      (Ig). The Fc domain forms a convenient 'tag' to enable detection of the protein
      in supernatant of transfected cells and for purification of immunogen by protein
      A affinity chromatography. The only requirement for immunogen preparation using
      this methodology is that a DNA sequence encoding a portion of the molecule of
      interest is known and that a suitable PCR template is available. Antibody
      production can be tailored to specific protein domains, for example functional
      domains, by expressing solely those domains in the fusion protein. We illustrate
      the technique with two different fusions used to raise antibodies against the
      porcine and human analogues of a complement (C) regulatory protein, decay
      accelerating factor (DAF) (CD55). Use of the specific Ig-fusion protein and a
      control protein facilitated screening of fusions by ELISA. We demonstrate two
      expression systems used to generate Ig fusion proteins, the first utilised a
      commercial vector to incorporate an amino terminal leader sequence and carboxy
      terminal Ig domains. Low levels of expression required subcloning into a high
      expression vector and resulted in yields of fusion protein at between 2 and 10 mg
      per litre of supernatant. The second expression system utilised the high
      expression vector directly, Ig domains of the chosen immunoglobulin isotype were
      amplified from peripheral blood mononuclear cell (PBMC) RNA and ligated into the
      vector in frame with DNA encoding the antigen. We describe potential pitfalls
      that may be encountered while using Ig fusion proteins as immunogen and
      demonstrate ways in which to tailor their design for optimal mAb production.

PMID- 12215409
TI  - DNA knotting caused by head-on collision of transcription and replication.
AB  - Collision of transcription and replication is uncommon, but the reason for nature
      to avoid this type of collision is still poorly understood. In Escherichia coli
      pBR322 is unstable and rapidly lost without selective pressure. Stability can be
      rescued if transcription of the tetracycline-resistance gene (Tet(R)),
      progressing against replication, is avoided. We investigated the topological
      consequences of the collision of transcription and replication in pBR322-derived
      plasmids where head-on collision between the replication fork and the RNA
      polymerase transcribing the Tet(R) gene was allowed or avoided. The results
      obtained indicate that this type of collision triggers knotting of the daughter
      duplexes behind the fork. We propose this deleterious topological consequence
      could explain the instability of pBR322 and could be also one of the reasons for
      nature to avoid head-on collision of transcription and replication.

PMID- 12215410
TI  - A cis-prolyl peptide bond isomerization dominates the folding of the alpha
      subunit of Trp synthase, a TIM barrel protein.
AB  - The cis/trans isomerization of prolyl peptide bonds has been suggested to
      dominate the folding of the alpha subunit of tryptophan synthase from Escherichia
      coli (alphaTS). To test the role of the unique cis isomer between Asp27 and
      Pro28, the folding properties of P28A, P28G and G(3)P28G, a three-glycine
      insertion mutant between Asp27 and Gly28, were investigated using urea as a
      denaturant. Circular dichroism analysis demonstrated that none of the mutations
      perturb the secondary structure significantly, although the aromatic side-chain
      packing is altered for P28A and P28G. All three mutant proteins inherited the
      three-state thermodynamic behavior observed in wild-type alphaTS, ensuring that
      the fundamental features of the energy surface are intact. Kinetic studies showed
      that neither alanine nor glycine substitutions at Pro28 results in the
      elimination of any slow-refolding phases. By contrast, the G(3)P28G mutant
      eliminates the fastest of the slow-refolding phases and one of the two unfolding
      phases. Double-jump experiments on G(3)P28G confirm the assignment of the missing
      refolding phase to the isomerization of the Asp27-Pro28 peptide bond. These
      results imply that the local stability conveyed by the tight, overlapping turns
      containing the cis peptide bond is sufficient to favor the cis isomer for several
      non-prolyl residues. The free energy required to drive the isomerization reaction
      is provided by the formation of the stable intermediate, demonstrating that the
      acquisition of structure and stability is required to induce subsequent rate
      limiting steps in the folding of alphaTS.

PMID- 12215411
TI  - Structural and biological characterisation of the gut-associated cyclophilin B
      isoforms from Caenorhabditis elegans.
AB  - The free-living nematode Caenorhabditis elegans expresses 18 cyclophilin
      isoforms, eight of which are conserved single domain forms, comprising two
      closely related secreted or type B forms (CYP-5 and CYP-6). Recombinant CYP-5 has
      been purified, crystallised and the X-ray structure solved to a resolution of
      1.75A. The detailed molecular architecture most strongly resembles the structure
      of human cyclophilin B with conserved changes in loop structure and N and C
      terminal extensions. Interestingly, the active site pocket is occupied by a
      molecule of dithiothreitol though this has little effect on the geometry of the
      active site which is similar to other cyclophilin structures. The peptidyl-prolyl
      isomerase activity of CYP-5 has been characterised against the substrate N
      succinyl-Ala-Ala-Pro-Phe-p-nitroanilide, and gives a k(cat)/K(m) value of
      3.6x10(6)M(-1)s(-1) that compares with a value of 6.3x10(6)M(-1)s(-1) for human
      cyclophilin B. The immunosuppressive drug cyclosporin A binds and inhibits CYP-5
      with an IC(50) value of 50nM, which is comparable to the value of 84nM found for
      human cyclophilin B. CYP-6 has 67% sequence identity with CYP-5 and a molecular
      model was built based on the CYP-5 crystal structure. The model shows that CYP-5
      and CYP-6 are likely to have very similar structures, but with a markedly
      increased number of negative charges distributed around the surface of CYP-6. The
      spatial expression patterns of the cyclophilin B isoforms were examined using
      transgenic animals carrying a LacZ reporter fusion to these genes, and both cyp-5
      and cyp-6 are found to be expressed in an overlapping fashion in the nematode
      gut. The temporal expression pattern of cyp-5 was further determined and revealed
      a constitutive expression pattern, with highest abundance levels being found in
      the embryo.

PMID- 12215412
TI  - Characterization of mutations in NOT2 indicates that it plays an important role
      in maintaining the integrity of the CCR4-NOT complex.
AB  - The NOT2 protein is a component of the CCR4-NOT complex that plays multiple roles
      in the regulation of mRNA production in the yeast Saccharomyces cerevisiae. We
      have identified four novel not2 mutations and have characterized these and two
      previously described alleles as to the means by which they affect CCR4-NOT
      function. While two of the not2 alleles, not2-4 (carrying a G31R alteration) and
      not2::L9P, resulted in severe growth defects and caused a not phenotype at the
      HIS3 locus, these phenotypes appear to arise from partially different effects.
      The not2::L9P mutation resulted in complete loss of the 1.9x10(6)Da (1.9MDa) CCR4
      NOT complex, and the not2::L9P protein displayed increased ability to associate
      with the NOT5 protein. In contrast, the not2-4 allele destabilized the CCR4-NOT
      complex to a lesser extent and had no effect on NOT5 association with NOT2.
      Instead, as previously reported, it displayed defective interactions with ADA2, a
      component of the SAGA complex. The not2::R165G also abrogated NOT2 ability to
      interact with ADA2 but had little effect on the integrity of the CCR4-NOT
      complex. Alterations in NOT2 contacts to ADA2, therefore, do not necessarily
      result in effects on the CCR4-NOT complex nor result in severe growth defects. We
      also observed that the four NOT2 N-terminal mutations affected NOT5 association
      with the CCR4-NOT complexes, suggesting that it is the N terminus of NOT2 that
      contacts and stabilizes NOT5 interactions. These results indicate that it is the
      loss of the integrity of the CCR4-NOT complex which leads to severe not2
      phenotypes and that the NOT2 contacts to ADA2 play a lesser role in NOT2
      function.

PMID- 12215413
TI  - Acetylation and accessibility of rDNA chromatin in Saccharomyces cerevisiae in
      (Delta)top1 and (Delta)sir2 mutants.
AB  - The insertion of reporter genes in the ribosomal DNA (rDNA) locus of
      Saccharomyces cerevisiae causes their transcriptional repression. This kind of
      transcriptional silencing depends on proteins such as Sir2p and Top1p, and has
      been shown to be mediated by chromatin. While Sir2p modifies nucleosomes directly
      through its histone deacetylase activity, little is known about changes in the
      chromatin structure that occur at the rDNA locus when TOP1 is deleted. Here, we
      show that the absence of Top1p causes increased histone acetylation at the rDNA
      locus. Moreover, rDNA chromatin becomes more accessible in a similar manner in
      both top1 and sir2 mutant strains.

PMID- 12215414
TI  - Loopy proteins appear conserved in evolution.
AB  - Over the last decade, structural biologists have unravelled many proteins that
      appear natively disordered. Common assumptions are that many of these proteins
      adopt structure through binding and that the structural flexibility enables them
      to adopt different functions. Here, we investigated regions of more than 70
      sequence-consecutive residues that have no regular secondary structure (NORS).
      Analysing 31 entirely sequenced organisms, we predicted five times as many
      proteins with NORS regions (loopy proteins) in eukaryotes (20%) than in
      prokaryotes and archaeas (4%). Thousands of these NORS regions were over 150
      residues long. The amino acid composition of NORS regions differed from that of
      loops in PDB. Although NORS proteins had significantly more residues in low
      complexity regions than other proteins, simple cut-off thresholds for sequence
      bias missed most NORS regions. On average, NORS regions were evolutionarily at
      least as conserved as their flanking regions. Furthermore, yeast proteins with
      NORS regions had more protein-protein interaction partners than other proteins.
      Regulatory and transcription-related functions were over-represented in loopy
      proteins, biosynthesis and energy metabolism were under-represented. Overall, our
      analysis confirmed that proteins with non-regular structures appear to play
      important functional roles, and they may adopt as yet unknown types of protein
      structures.

PMID- 12215415
TI  - De novo prediction of three-dimensional structures for major protein families.
AB  - We use the Rosetta de novo structure prediction method to produce three
      dimensional structure models for all Pfam-A sequence families with average length
      under 150 residues and no link to any protein of known structure. To estimate the
      reliability of the predictions, the method was calibrated on 131 proteins of
      known structure. For approximately 60% of the proteins one of the top five models
      was correctly predicted for 50 or more residues, and for approximately 35%, the
      correct SCOP superfamily was identified in a structure-based search of the
      Protein Data Bank using one of the models. This performance is consistent with
      results from the fourth critical assessment of structure prediction (CASP4).
      Correct and incorrect predictions could be partially distinguished using a
      confidence function based on a combination of simulation convergence, protein
      length and the similarity of a given structure prediction to known protein
      structures. While the limited accuracy and reliability of the method precludes
      definitive conclusions, the Pfam models provide the only tertiary structure
      information available for the 12% of publicly available sequences represented by
      these large protein families.

PMID- 12215416
TI  - Trimeric crystal structure of the glycoside hydrolase family 42 beta
      galactosidase from Thermus thermophilus A4 and the structure of its complex with
      galactose.
AB  - The beta-galactosidase from an extreme thermophile, Thermus thermophilus A4 (A4
      beta-Gal), is thermostable and belongs to the glycoside hydrolase family 42 (GH
      42). As the first known structures of a GH-42 enzyme, we determined the crystal
      structures of free and galactose-bound A4-beta-Gal at 1.6A and 2.2A resolution,
      respectively. A4-beta-Gal forms a homotrimeric structure resembling a flowerpot.
      Each monomer has an active site located inside a large central tunnel. The N
      terminal domain of A4-beta-Gal has a TIM barrel fold, as predicted from
      hydrophobic cluster analysis. The putative catalytic residues of A4-beta-Gal
      (Glu141 and Glu312) superimpose well with the catalytic residues of Escherichia
      coli beta-galactosidase. The environment around the catalytic nucleophile
      (Glu312) is similar to that in the case of E.coli beta-galactosidase, but the
      recognition mechanism for a substrate is different. Trp182 of the next subunit of
      the trimer constitutes a part of the active-site pocket, indicating that the
      trimeric structure is essential for the enzyme activity. Structural comparison
      with other glycoside hydrolases revealed that many features of the 4/7
      superfamily are conserved in the A4-beta-Gal structure. On the basis of the
      results of 1H NMR spectroscopy, A4-beta-Gal was determined to be a "retaining"
      enzyme. Interestingly, the active site was similar with those of retaining
      enzymes, but the overall fold of the TIM barrel domain was very similar to that
      of an inverting enzyme, beta-amylase.

PMID- 12215417
TI  - Structural basis for AMPA receptor activation and ligand selectivity: crystal
      structures of five agonist complexes with the GluR2 ligand-binding core.
AB  - Glutamate is the principal excitatory neurotransmitter within the mammalian CNS,
      playing an important role in many different functions in the brain such as
      learning and memory. In this study, a combination of molecular biology, X-ray
      structure determinations, as well as electrophysiology and binding experiments,
      has been used to increase our knowledge concerning the ionotropic glutamate
      receptor GluR2 at the molecular level. Five high-resolution X-ray structures of
      the ligand-binding domain of GluR2 (S1S2J) complexed with the three agonists (S)
      2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl]propionic acid (2
      Me-Tet-AMPA), (S)-2-amino-3-(3-carboxy-5-methylisoxazol-4-yl)propionic acid
      (ACPA), and (S)-2-amino-3-(4-bromo-3-hydroxy-isoxazol-5-yl)propionic acid (Br
      HIBO), as well as of a mutant thereof (S1S2J-Y702F) in complex with ACPA and Br
      HIBO, have been determined. The structures reveal that AMPA agonists with an
      isoxazole moiety adopt different binding modes in the receptor, dependent on the
      substituents of the isoxazole. Br-HIBO displays selectivity among different AMPA
      receptor subunits, and the design and structure determination of the S1S2J-Y702F
      mutant in complex with Br-HIBO and ACPA have allowed us to explain the molecular
      mechanism behind this selectivity and to identify key residues for ligand
      recognition. The agonists induce the same degree of domain closure as AMPA,
      except for Br-HIBO, which shows a slightly lower degree of domain closure. An
      excellent correlation between domain closure and efficacy has been obtained from
      electrophysiology experiments undertaken on non-desensitising GluR2i(Q)-L483Y
      receptors expressed in oocytes, providing strong evidence that receptor
      activation occurs as a result of domain closure. The structural results, combined
      with the functional studies on the full-length receptor, form a powerful platform
      for the design of new selective agonists.

PMID- 12215418
TI  - Structures of two kinetic intermediates reveal species specificity of penicillin
      binding proteins.
AB  - Penicillin-binding proteins (PBPs), the target enzymes of beta-lactam antibiotics
      such as penicillins and cephalosporins, catalyze the final peptidoglycan cross
      linking step of bacterial cell-wall biosynthesis. beta-Lactams inhibit this
      reaction because they mimic the D-alanyl-D-alanine peptide precursors of cell
      wall structure. Prior crystallographic studies have described the site of beta
      lactam binding and inhibition, but they have failed to show the binding of D-Ala
      D-Ala substrates. We present here the first high-resolution crystallographic
      structures of a PBP, D-Ala-D-Ala-peptidase of Streptomyces sp. strain R61, non
      covalently complexed with a highly specific fragment (glycyl-L-alpha-amino
      epsilon-pimelyl-D-Ala-D-Ala) of the cell-wall precursor in both enzyme-substrate
      and enzyme-product forms. The 1.9A resolution structure of the enzyme-substrate
      Henri-Michaelis complex was achieved by using inactivated enzyme, which was
      formed by cross-linking two catalytically important residues Tyr159 and Lys65.
      The second structure at 1.25A resolution of the uncross-linked, active form of
      the DD-peptidase shows the non-covalent binding of the two products of the
      carboxypeptidase reaction. The well-defined substrate-binding site in the two
      crystallographic structures shows a subsite that is complementary to a portion of
      the natural cell-wall substrate that varies among bacterial species. In addition,
      the structures show the displacement of 11 water molecules from the active site,
      the location of residues responsible for substrate binding, and clearly
      demonstrate the necessity of Lys65 and or Tyr159 for the acylation step with the
      donor peptide. Comparison of the complexed structures described here with the
      structures of other known PBPs suggests the design of species-targeted
      antibiotics as a counter-strategy towards beta-lactamase-elicited bacterial
      resistance.

PMID- 12215419
TI  - Hydrophobic interactions at the Ccap position of the C-capping motif of alpha
      helices.
AB  - We investigated the possible role of residues at the Ccap position in an alpha
      helix on protein stability. A set of 431 protein alpha-helices containing a C'
      Gly from the Protein Data Bank (PDB) was analyzed, and the normalized frequencies
      for finding particular residues at the Ccap position, the average fraction of
      buried surface area, and the hydrogen bonding patterns of the Ccap residue side
      chain were calculated. We found that on average the Ccap position is 70% buried
      and noted a significant correlation (R=0.8) between the relative burial of this
      residue and its hydrophobicity as defined by the Gibbs energy of transfer from
      octanol or cyclohexane to water. Ccap residues with polar side-chains are
      commonly involved in hydrogen bonding. The hydrogen bonding pattern is such that,
      the longer side-chains of Glu, Gln, Arg, Lys, His form hydrogen bonds with
      residues distal (>+/-4) in sequence, while the shorter side-chains of Asp, Asn,
      Ser, Thr exhibit hydrogen bonds with residues close in sequence (<+/-4), mainly
      involving backbone atoms. Experimentally we determined the thermodynamic
      propensities of residues at the Ccap position using the protein ubiquitin as a
      model system. We observed a large variation in the stability of the ubiquitin
      variants depending on the nature of the Ccap residue. Furthermore, the measured
      changes in stability of the ubiquitin variants correlate with the hydrophobicity
      of the Ccap residue. The experimental results, together with the statistical
      analysis of protein structures from the PDB, indicate that the key hydrophobic
      capping interactions between a helical residue (C3 or C4) and a residue outside
      the helix (C", C3' or C4') are frequently enhanced by the hydrophobic
      interactions with Ccap residues.

PMID- 12215420
TI  - Intramolecular dynamics of low molecular weight protein tyrosine phosphatase in
      monomer-dimer equilibrium studied by NMR: a model for changes in dynamics upon
      target binding.
AB  - Low molecular weight protein tyrosine phosphatase (LMW-PTP) dimerizes in the
      phosphate-bound state in solution with a dissociation constant of K(d)=1.5(+/
      0.1)mM and an off-rate on the order of 10(4)s(-1). 1H and 15N NMR chemical shifts
      identify the dimer interface, which is in excellent agreement with that observed
      in the crystal structure of the dimeric S19A mutant. Two tyrosine residues of
      each molecule interact with the active site of the other molecule, implying that
      the dimer may be taken as a model for a complex between LMW-PTP and a target
      protein. 15N relaxation rates for the monomeric and dimeric states were
      extrapolated from relaxation data acquired at four different protein
      concentrations. Relaxation data of satisfactory precision were extracted for the
      monomer, enabling model-free analyses of backbone fluctuations on pico- to
      nanosecond time scales. The dimer relaxation data are of lower quality due to
      extrapolation errors and the possible presence of higher-order oligomers at
      higher concentrations. A qualitative comparison of order parameters in the
      monomeric and apparent dimeric states shows that loops forming the dimer
      interface become rigidified upon dimerization. Qualitative information on monomer
      dimer exchange and intramolecular conformational exchange was obtained from the
      concentration dependence of auto- and cross-correlated relaxation rates. The loop
      containing the catalytically important Asp129 fluctuates between different
      conformations in both the monomeric and dimeric (target bound) states. The
      exchange rate compares rather well with that of the catalyzed reaction step,
      supporting existing hypotheses that catalysis and enzyme dynamics may be coupled.
      The side-chain of Trp49, which is important for substrate specificity, exhibits
      conformational dynamics in the monomer that are largely quenched upon formation
      of the dimer, suggesting that binding is associated with the selection of a
      single side-chain conformer.

PMID- 12215421
TI  - DNA-induced partial unfolding of prion protein leads to its polymerisation to
      amyloid.
AB  - The full-length mouse recombinant prion protein (23-231 amino acid residues)
      contains all of its structural elements viz. three alpha-helices and a short two
      stranded antiparallel beta-sheet in its C-terminal fragment comprising 121-231
      amino acid residues. The incubated mixture of this prion protein fragment and
      nucleic acid results in the formation of amyloid fibres evidenced from electron
      microscopy, birefringence and fluorescence of the fibre bound Congo Red and
      Thioflavin T dyes, respectively. The secondary structure of the amyloid formed in
      nucleic acid solution is similar to the in vivo isolated prion protein 27-30
      amyloid but unlike in it, a hydrophobic milieu is absent in the 121-231 amyloid.
      Thermal denaturation study demonstrates a partial unfolding of the protein
      fragment in nucleic acid solution. We propose that nucleic acid catalyses
      unfolding of prion protein helix 1 followed by a nucleation-dependent
      polymerisation of the protein to amyloid.

PMID- 12215422
TI  - Cooperative interactions and a non-native buried Trp in the unfolded state of an
      SH3 domain.
AB  - The presence of residual structure in the unfolded state of the N-terminal SH3
      domain of Drosophila drk (drkN SH3 domain) has been investigated using far- and
      near-UV circular dichroism (CD), fluorescence, and NMR spectroscopy. The unfolded
      (U(exch)) state of the drkN SH3 domain is significantly populated and exists in
      equilibrium with the folded (F(exch)) state under non-denaturing conditions near
      physiological pH. Denaturation experiments have been performed on the drkN SH3
      domain in order to monitor the change in ellipticity, fluorescence intensity, and
      chemical shift between the U(exch) state and chemically or thermally denatured
      states. Differences between the unfolded and chemically or thermally denatured
      states highlight specific areas of residual structure in the unfolded state that
      are cooperatively disrupted upon denaturation. Results provide evidence for
      cooperative interactions in the unfolded state involving residues of the central
      beta-sheet, particularly the beta4 strand. Denaturation as well as hydrogen
      exchange experiments demonstrate a non-native burial of the Trp ring within this
      "cooperative" core of the unfolded state. These findings support the presence of
      non-native hydrophobic clusters, organised by Trp rings, within disordered
      states.

PMID- 12215423
TI  - Quantifying beta-sheet stability by phage display.
AB  - The small immunoglobulin G (IgG)-binding protein GB1 is a favored model system
      for the study of individual residue contributions to the stability of beta
      sheets. Nevertheless, only a few of the many possible combinations of mutations
      have been characterized, leaving many questions unanswered. In order to allow the
      simultaneous evaluation of libraries of mutants, we have adapted a phage-display
      method, called shotgun scanning. This method combines a binding (i.e. stability)
      selection with high-throughput sequence analysis. Relative folding free energies
      determined from GB1-phage sequence data agree well with published GB1 thermal
      stability studies, validating the use of phage display to conduct quantitative
      stability studies on GB1, and further suggesting that this method is generally
      applicable to mutational analysis of protein stability. Examination of residue
      pairing in our large collection of GB1 mutants indicates that specific side-chain
      side-chain interactions are much less important to beta-sheet stability than
      individual residue contributions. The discrepancy between this observation and
      published studies can be traced to anomalous stability of the alanine-substituted
      GB1 variants typically used as reference states in double mutant-cycle analyses.
      Finally, the combination of large library sizes and a quantitative stability
      selection should allow phage-based "computation" to be applied to protein design
      problems.

PMID- 12215424
TI  - Increasing temperature accelerates protein unfolding without changing the pathway
      of unfolding.
AB  - We have traditionally relied on extremely elevated temperatures (498K, 225
      degrees C) to investigate the unfolding process of proteins within the timescale
      available to molecular dynamics simulations with explicit solvent. However,
      recent advances in computer hardware have allowed us to extend our thermal
      denaturation studies to much lower temperatures. Here we describe the results of
      simulations of chymotrypsin inhibitor 2 at seven temperatures, ranging from 298K
      to 498K. The simulation lengths vary from 94ns to 20ns, for a total simulation
      time of 344ns, or 0.34 micros. At 298K, the protein is very stable over the full
      50ns simulation. At 348K, corresponding to the experimentally observed melting
      temperature of CI2, the protein unfolds over the first 25ns, explores partially
      unfolded conformations for 20ns, and then refolds over the last 35ns. Above its
      melting temperature, complete thermal denaturation occurs in an activated
      process. Early unfolding is characterized by sliding or breathing motions in the
      protein core, leading to an unfolding transition state with a weakened core and
      some loss of secondary structure. After the unfolding transition, the core
      contacts are rapidly lost as the protein passes on to the fully denatured
      ensemble. While the overall character and order of events in the unfolding
      process are well conserved across temperatures, there are substantial differences
      in the timescales over which these events take place. We conclude that 498K
      simulations are suitable for elucidating the details of protein unfolding at a
      minimum of computational expense.

PMID- 12215425
TI  - Sequence conservation in families whose members have little or no sequence
      similarity: the four-helical cytokines and cytochromes.
AB  - Proteins for which there are good structural, functional and genetic similarities
      that imply a common evolutionary origin, can have sequences whose similarities
      are low or undetectable by conventional sequence comparison procedures. Do these
      proteins have sequence conservation beyond the simple conservation of hydrophobic
      and hydrophilic character at specific sites and if they do what is its nature? To
      answer these questions we have analysed the structures and sequences of two
      superfamilies: the four-helical cytokines and cytochromes c'-b(562). Members of
      these superfamilies have sequence similarities that are either very low or not
      detectable. The cytokine superfamily has within it a long chain family and a
      short chain family. The sequences of known representative structures of the two
      families were aligned using structural information. From these alignments we
      identified the regions that conserve the same main-chain conformation: the common
      core (CC). For members of the same family, the CC comprises some 50% of the
      individual structures; for the combination of both families it is 30%. We added
      homologous sequences to the structural alignment. Analysis of the residues
      occurring at sites within the CCs showed that 30% have little or no conservation,
      whereas about 40% conserve the polar/neutral or hydrophobic/neutral character of
      their residues. The remaining 30% conserve hydrophobic residues with strong or
      medium limitations on their volume variations. Almost all of these residues are
      found at sites that form the "buried spine" of each helix (at sites i, i+3, i+7,
      i+10, etc., or i, i+4, i+7, i+11, etc.) and they pack together at the centre of
      each structure to give a pattern of residue-residue contacts that is almost
      absolutely conserved. These CC conserved hydrophobic residues form only 10-15% of
      all the residues in the individual structures.A similar analysis of the
      cytochromes c'-b(562), which bind haem and have a very different function to that
      of the cytokines, gave very similar results. Again some 30% of the CC residues
      have hydrophobic residues with strong or medium conservation. Most of these form
      the buried spine of each helix and play the same role as those in the cytokines.
      The others, and some spine residues bind the haem co-factor.

PMID- 12215426
TI  - Regulation and function of LEFTY-A/EBAF in the human endometrium. mRNA expression
      during the menstrual cycle, control by progesterone, and effect on matrix
      metalloprotineases.
AB  - The human endometrium is a unique tissue that is periodically shed during
      menstruation. Although overall triggered by ovarian steroids withdrawal,
      menstrual induction of matrix metalloproteinases (MMPs) and resulting tissue
      breakdown are focal responses, pointing to additional local modulators. LEFTY-A,
      a novel member of the transforming growth factor-beta family identified
      originally as an endometrial bleeding-associated factor (EBAF), is a candidate
      for this local control. We measured LEFTY-A and beta-ACTIN mRNA concentration
      during the menstrual cycle in vivo and found that their ratio was dramatically (
      approximately 100-fold) increased at the perimenstrual phase. A similar increase
      was seen when proliferative explants were cultured for 24 h in the absence of
      ovarian steroids; this was followed by spontaneous production of proMMP-1, -3,
      and -9. Both responses were inhibited by progesterone. Moreover, addition of
      recombinant LEFTY-A to proliferative explants was sufficient to stimulate the
      expression of proMMP-3 and -7; this response was also blocked by ovarian
      steroids. Collectively, these data indicate that LEFTY-A may provide a crucial
      signal for endometrial breakdown and bleeding by triggering expression of several
      MMPs. Progesterone appears to exert a dual block, upstream by inhibiting LEFTY-A
      expression and downstream by suppressing its stimulatory effect on MMPs.

PMID- 12215427
TI  - Interaction with Nedd8, a ubiquitin-like protein, enhances the transcriptional
      activity of the aryl hydrocarbon receptor.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated member of the basic
      helix-loop-helix period aryl hydrocarbon nuclear translocator single-minded (PAS)
      transcription factor family. This receptor has been shown to be important in
      various aspects of growth and development as demonstrated by AhR-null mice. A
      yeast two-hybrid screen of a mouse embryonic day 11 library for AhR-interacting
      proteins revealed Nedd8 as a candidate. The interaction was confirmed in a cell
      free system and in mammalian cells by co-immunoprecipitation; however, in vitro
      neddylation assays showed that Nedd8 does not covalently modify AhR. Transfection
      of Nedd8 into a cell line stably transfected with a dioxin response element
      linked to a chloramphenicol acetyltransferase reporter gene demonstrated that
      Nedd8 amplified ligand-induced transcription. Deletion of the Gly-76 residue in
      the carboxyl terminus of Nedd8 abolished this effect and prevented AhR-Nedd8
      interaction. Nedd8 overexpression also resulted in accumulation of AhR protein in
      the nucleus, independent of exogenous ligand. These studies demonstrate that the
      AhR interacts with Nedd8 and suggest that this interaction enhances the
      transcriptional activity of the receptor, perhaps involving increased nuclear
      accumulation or retention. Immunohistochemistry performed on embryonic day 11.5
      mouse sections indicated Nedd8 and AhR localize to overlapping areas in the heart
      and spinal ganglia, raising the possibility that this interaction may play a role
      in organogenesis.

PMID- 12215428
TI  - Suppression of nuclear factor-kappa B activity by nitric oxide and hyperoxia in
      oxygen-resistant cells.
AB  - Inhaled nitric oxide (iNO) is used clinically to treat pulmonary hypertension in
      newborns, often in conjunction with hyperoxia (NO/O2). Prolonged exposure to
      NO/O2 causes synergistic lung injury and death of lung epithelial cells. To
      explore the mechanisms involved, oxygen-resistant HeLa-80 cells were exposed to
      NO +/- O2. Exposure to NO and O2 induced a synergistic cytotoxicity, accompanied
      with apoptotic characteristics, including elevated caspase-3-like activity,
      Annexin V incorporation, and nuclear condensation. This apoptosis was associated
      with a synergistic suppression of NF-kappaB activity. Cells lacking functional NF
      kappaB p65 subunit were more sensitive to NO/O2 than their wild type
      counterparts. This injury was partially rescued by transfection with a p65
      expression construct, suggesting an inverse relationship between NF-kappaB and
      susceptibility to the cytotoxicity of NO/O2. Despite the reduced NF-kappaB
      activity in cells exposed to NO +/- O2, IkappaBalpha was degraded, suggesting
      that pathways regulating the steady-state levels of IkappaB were not involved.
      However, exposure to NO/O2 caused a marked reduction in nuclear localization and
      an increase in protein carbonyl formation of NF-kappaB p65 subunit. These results
      suggest that NO/O2-induced apoptosis occurs by suppressing NF-kappaB activity.

PMID- 12215430
TI  - Analysis of the catalytic domain of phosphatidylinositol 4-kinase type II.
AB  - Phosphatidylinositol (PtdIns) 4-kinases catalyze the conversion of PtdIns to
      PtdIns 4-phosphate, the major precursor of phosphoinositides that regulates a
      vast array of cellular processes. Based on enzymatic differences, two classes of
      PtdIns 4-kinase have been distinguished termed Types II and III. Type III
      kinases, which belong to the phosphatidylinositol (PI) 3/4-kinase family, have
      been extensively characterized. In contrast, little is known about the Type II
      enzymes (PI4KIIs), which have been cloned and sequenced very recently. PI4KIIs
      bear essentially no sequence similarity to other protein or lipid kinases; hence,
      they represent a novel and distinct branch of the kinase superfamily. Here we
      define the minimal catalytic domain of a rat PI4KII isoform, PI4KIIalpha, and
      identify conserved amino acid residues required for catalysis. We further show
      that the catalytic domain by itself determines targeting of the kinase to
      membrane rafts. To verify that the PI4KII family extends beyond mammalian
      sources, we expressed and characterized Drosophila PI4KII and its catalytic
      domain. Depletion of PI4KII from Drosophila cells resulted in a severe reduction
      of PtdIns 4-kinase activity, suggesting the in vivo importance of this enzyme.

PMID- 12215429
TI  - A Crk-II/TC10 signaling pathway is required for osmotic shock-stimulated glucose
      transport.
AB  - Osmotic shock stimulates the translocation of the glucose transporter Glut 4 to
      plasma membrane by a tyrosine kinase signaling pathway involving Gab-1 (the Grb2
      associated binder-1 protein). We show here that, in response to osmotic shock,
      Gab-1 acts as a docking protein for phospholipase Cgamma1, the p85 subunit of the
      phosphoinositide 3-kinase and Crk-II. It has been shown that the adapter Crk-II
      is constitutively associated with C3G, a GDP to GTP exchange factor for several
      small GTP-binding proteins. We found that inhibition of the activity of
      phosphoinositide 3-kinase or phospholipase C did not prevent the stimulation of
      glucose transport by osmotic shock, whereas inactivation of Rho proteins by
      Clostridium difficile toxin B severely inhibited glucose uptake. Among the Rho
      family members, overexpression of dominant-interfering TC10/T31N mutant inhibited
      osmotic shock-mediated Glut 4 translocation suggesting that TC10 is required for
      this process. Further, disruption of cortical actin integrity by latrunculin B or
      jasplakinolide severely impaired osmotic shock-induced glucose transport. In
      contrast, osmotic shock increased the amount of cortical actin associated with
      caveolin-enriched plasma membrane domains. These data provide the first evidence
      that activation of TC10 and remodeling of cortical actin, which could occur
      through the TC10 signaling, are required for osmotic shock-mediated Glut 4
      translocation and glucose uptake.

PMID- 12215431
TI  - An intramolecular disulfide bridge as a catalytic switch for serotonin N
      acetyltransferase.
AB  - Serotonin N-acetyltransferase (EC. 2.3.1.87) (AA-NAT) is a melatonin rhythm
      generating enzyme in pineal glands. To establish a melatonin rhythm, AA-NAT
      activity is precisely regulated through several signaling pathways. Here we show
      novel regulation of AA-NAT activity, in which an intramolecular disulfide bond
      may function as a switch for the catalysis. Recombinant AA-NAT activity was
      irreversibly inhibited by N-ethylmaleimide (NEM) in an acetyl-CoA-protected
      manner. Oxidized glutathione or dissolved oxygen reversibly inhibited AA-NAT in
      an acetyl-CoA-protected manner. To identify the cysteine residues responsible for
      the inhibition, AA-NAT was first oxidized with dissolved oxygen, treated with
      NEM, reduced with dithiothreitol, and then labeled with [(14)C]NEM. Cys(61) and
      Cys(177) were specifically labeled in an acetyl-CoA-protected manner. The AA-NAT
      with the Cys(61) to Ala and Cys(177) to Ala double substitutions (C61A/C177A-AA
      NAT) was fully active but did not exhibit sensitivity to either oxidation or NEM,
      whereas the AA-NATs with only the single substitutions retained about 40% of
      these sensitivities. An intramolecular disulfide bond between Cys(61) and
      Cys(177) formed upon oxidation and cleaved upon reduction was identified.
      Furthermore, C61A/C177A-AA-NAT expressed in COS7 cells was relatively insensitive
      to H(2)O(2)-evoked oxidative stress, whereas wild-type AA-NAT was strongly
      inhibited under the same conditions. These results indicate that the formation
      and cleavage of the disulfide bond between Cys(61) and Cys(177) produce the
      active and inactive states of AA-NAT. It is possible that intracellular redox
      conditions regulate AA-NAT activity through switching via an intramolecular
      disulfide bridge.

PMID- 12215432
TI  - Identification of a Drosophila gene encoding xylosylprotein beta4
      galactosyltransferase that is essential for the synthesis of glycosaminoglycans
      and for morphogenesis.
AB  - In mammals, the xylosylprotein beta4-galactosyltransferase termed beta4GalT7
      (XgalT-1, EC ) participates in proteoglycan biosynthesis through the transfer of
      galactose to the xylose that initiates each glycosaminoglycan chain. A Drosophila
      cDNA homologous to mammalian beta4-galactosyltransferases was identified using a
      human beta4GalT7 cDNA as a probe in a BLAST analysis of expressed sequence tags.
      The Drosophila cDNA encodes a type II membrane protein with 322 amino acids and
      shows 49% identity to human beta4GalT7. Extracts from L cells transfected with
      the cDNA exhibited marked galactosyltransferase activity specific for a
      xylopyranoside acceptor. Moreover, transfection with the cloned cDNA restored
      glycosaminoglycan synthesis in beta4GalT7-deficient Chinese hamster ovary cells.
      In transfectant lysates the properties of Drosophila and human beta4GalT7
      resembled each other, except that Drosophila beta4GalT7 showed a less restricted
      specificity and was active at a wider range of temperatures. Drosophila
      beta4GalT7 is expressed throughout development, with higher expression levels in
      adults. Reduction of Drosophila beta4GalT7 levels using expressed RNA
      interference (RNAi) in imaginal discs resulted in an abnormal wing and leg
      morphology similar to that of flies with defective Hedgehog and Decapentaplegic
      signaling, which are known to depend on intact proteoglycan biosynthesis.
      Immunohistochemical analysis of tissues confirmed that both heparan sulfate and
      chondroitin sulfate biosynthesis were impaired. Our results demonstrate that
      Drosophila beta4GalT7 has the in vitro and in vivo properties predicted for an
      ortholog of human beta4GalT7 and is essential for normal animal development
      through its role in proteoglycan biosynthesis.

PMID- 12215433
TI  - Differential splicing generates Tvl-1/RFXANK isoforms with different functions.
AB  - Earlier studies have shown that Tvl-1 gives rise to at least two differentially
      spliced mRNAs, one of which (Tvl-S) encodes a protein that lacks amino acids 91
      112. DNA binding of RFX complexes assembled in the presence of Tvl-S is impaired.
      As a result, Tvl-S does not support the expression of Class II major
      histocompatibility complex (MHC) genes. Here, we show that the reason Tvl-S is
      inactive as a transcriptional regulator of Class II MHC genes is that the RFX
      complexes assembled in the presence of Tvl-S are unstable. Additionally, we show
      that interferon-gamma, which induces Class II MHC gene expression in 293 cells,
      promotes a shift in the splicing pattern of RFXANK/Tvl-1 toward the
      transcriptionally active Tvl-L isoform, suggesting that differential splicing of
      Tvl-1 is a signal-regulated process. Finally, we show that Tvl-1 regulates the
      expression of non-MHC genes. One such gene encodes the ephrin receptor EphA3.
      Since both Tvl-L and Tvl-S are identical in their ability to induce the
      expression of EphA3, we conclude that Tvl-1 regulates the expression of non-MHC
      genes by RFX-independent mechanisms.

PMID- 12215434
TI  - Overexpression of Alzheimer's disease amyloid-beta opposes the age-dependent
      elevations of brain copper and iron.
AB  - Increased brain metal levels have been associated with normal aging and a variety
      of diseases, including Alzheimer's disease (AD). Copper and iron levels both show
      marked increases with age and may adversely interact with the amyloid-beta
      (Abeta) peptide causing its aggregation and the production of neurotoxic hydrogen
      peroxide (H(2)O(2)), contributing to the pathogenesis of AD. Amyloid precursor
      protein (APP) possesses copper/zinc binding sites in its amino-terminal domain
      and in the Abeta domain. Here we demonstrate that overexpression of the carboxyl
      terminal fragment of APP, containing Abeta, results in significantly reduced
      copper and iron levels in transgenic mouse brain, while overexpression of the APP
      in Tg2576 transgenic mice results in significantly reduced copper, but not iron,
      levels prior to the appearance of amyloid neuropathology and throughout the
      lifespan of the mouse. Concomitant increases in brain manganese levels were
      observed with both transgenic strains. These findings, complemented by our
      previous findings of elevated copper levels in APP knock-out mice, support roles
      for APP and Abeta in physiological metal regulation.

PMID- 12215435
TI  - Cyclosporine inhibits growth through the activating transcription factor/cAMP
      responsive element-binding protein binding site in the cyclin D1 promoter.
AB  - The immunosuppressive agent cyclosporine affects proliferation depending on the
      cellular system used. In an attempt to study the inhibitory effect of
      cyclosporine on proliferation of pancreatic acinar cells, we used AR42J cells as
      a model system. Here we demonstrate that cyclosporine inhibits growth of these
      cells by inducing G(1) cell cycle arrest. This effect is mediated by the 5'
      regulatory region of the cyclin D1 gene and leads to a reduction of cyclin D1
      mRNA expression and protein abundance. We show that in AR42J cells the proximal
      cyclin D1 promoter contains a cis-regulated element, which is important for the
      maintenance of basal transcriptional activity. This element overlaps the
      described cAMP-responsive element (CRE) and confers cyclosporine sensitivity to
      the cyclin D1 promoter. Furthermore, the DNA binding activity of the CRE-binding
      protein (CREB) decreases through cyclosporine treatment and this is mediated by
      cyclosporine-induced reduction of CREB steady-state levels. These results
      demonstrate that cyclosporine can inhibit proliferation of acinar cells by
      targeting the cyclin D1 promoter at the proximal CRE via a reduction of CREB
      protein abundance.

PMID- 12215436
TI  - Prostaglandin E2 suppresses chemokine production in human macrophages through the
      EP4 receptor.
AB  - Pro-inflammatory pathways participate in the pathogenesis of atherosclerosis.
      However, the role of endogenous anti-inflammatory pathways in atheroma has
      received much less attention. Therefore, using cDNA microarrays, we screened for
      genes regulated by prostaglandin E(2) (PGE(2)), a potential endogenous anti
      inflammatory mediator, in lipopolysaccharide (LPS)-treated human macrophages
      (MPhi). PGE(2) (50 nm) attenuated LPS-induced mRNA and protein expression of
      chemokines including monocyte chemoattractant protein-1, interleukin-8,
      macrophage inflammatory protein-1alpha and -1beta, and interferon-inducible
      protein-10. PGE(2) also inhibited the tumor necrosis factor-alpha-, interferon
      gamma-, and interleukin-1beta-mediated expression of these chemokines. In
      contrast to the case of MPhi, PGE(2) did not suppress chemokine expression in
      human endothelial and smooth muscle cells (SMC) treated with LPS and pro
      inflammatory cytokines. To assess the potential paracrine effect of endogenous
      PGE(2) on macrophage-derived chemokine production, we co-cultured MPhi with SMC
      in the presence of LPS. In these co-cultures, cyclooxygenase-2-dependent PGE(2)
      production exceeded that in the mono-cultures, and MIP-1beta declined
      significantly compared with MPhi cultured without SMC. We further documented
      prominent expression of the PGE(2) receptor EP4 in MPhi in both culture and human
      atheroma. Moreover, a selective EP4 antagonist completely reversed PGE(2)
      mediated suppression of chemokine production. Thus, endogenous PGE(2) may
      modulate inflammation during atherogenesis and other inflammatory diseases by
      suppressing macrophage-derived chemokine production via the EP4 receptor.

PMID- 12215437
TI  - Dermatan sulfate binds and potentiates activity of keratinocyte growth factor
      (FGF-7).
AB  - FGF-7 is induced after injury and induces the proliferation of keratinocytes.
      Like most members of the FGF family, the activity of FGF-7 is strongly influenced
      by binding to heparin, but this glycosaminoglycan is absent on keratinocyte cell
      surfaces and minimally present in the wound environment. In this investigation we
      compared the relative activity of heparan sulfate and chondroitin sulfate B
      (dermatan sulfate), glycosaminoglycans that are present in wounds. A lymphoid
      cell line (BaF/KGFR) containing the FGF-7 receptor (FGFR2 IIIb) was treated with
      FGF-7 and with various glycosaminoglycans. FGF-7 did not support cell
      proliferation in the absence of glycosaminoglycan or with addition of heparan
      sulfate or chondroitin sulfate A/C but did stimulate BaF/KGFR division in the
      presence of dermatan sulfate or highly sulfated low molecular weight fractions of
      dermatan. Dermatan sulfate also enabled FGF-7-dependent phosphorylation of
      mitogen-activated protein kinase and promoted binding of radiolabeled FGF-7 to
      FGFR2 IIIb. In addition, dermatan sulfate and FGF-7 stimulated growth of normal
      keratinocytes in culture. Thus, dermatan sulfate, the predominant
      glycosaminoglycan in skin, is the principle cofactor for FGF-7.

PMID- 12215438
TI  - Direct in vivo screening of intrabody libraries constructed on a highly stable
      single-chain framework.
AB  - Single-chain Fv antibody fragments (scFv) represent a convenient antibody format
      for intracellular expression in eukaryotic or prokaryotic cells. These so-called
      intrabodies have great potential in functional genomics as a tool to study the
      function of newly identified proteins in vivo, for example by binding-induced
      modulation of their activity or by blocking interactions with other proteins.
      However, the intracellular expression and activity of many single-chain Fvs are
      limited by their instability and folding efficiency in the reducing intracellular
      environment, where the highly conserved intrachain disulfide bonds do not form.
      In the present work, we used an in vivo selection system to isolate novel antigen
      binding intrabodies. We screened two intrabody libraries carrying a randomized
      third hypervariable loop onto the heavy chain of a stable framework, which had
      been further optimized by random mutagenesis for better behavior in the selection
      system, and we biophysically characterized the selected variants to interpret the
      outcome of the selection. Our results show that single-framework intrabody
      libraries can be directly screened in vivo to rapidly select antigen-specific
      intrabodies.

PMID- 12215439
TI  - Ubiquitylation of the transducin betagamma subunit complex. Regulation by
      phosducin.
AB  - G proteins (Galphabetagamma) are essential signaling molecules, which dissociate
      into Galpha and Gbetagamma upon activation by heptahelical membrane receptors. We
      have identified the betagamma subunit complex of the photoreceptor-specific G
      protein, transducin (T), as a target of the ubiquitin-proteasome pathway.
      Ubiquitylated species of the transducin gamma-subunit (Tgamma) but not the alpha-
      or beta-subunits were assembled de novo in bovine photoreceptor preparations. In
      addition, Tgamma was exclusively ubiquitylated when Tbetagamma was dissociated
      from Talpha. Ubiquitylation of Tbetagamma on Tgamma was selectively catalyzed by
      human ubiquitin-conjugating enzymes UbcH5 and UbcH7 and was coincident with
      degradation of the entire Tbetagamma subunit complex in vitro by a mechanism
      requiring ATP and the proteasome. We also show that Tbetagamma association with
      phosducin, a photoreceptor-specific protein of unknown physiological function,
      blocks Tbetagamma ubiquitylation and subsequent degradation. Phosphorylation of
      phosducin by Ca(2+)/calmodulin-dependent protein kinase II, which inhibits
      phosducin-Tbetagamma complex formation, completely restored Tbetagamma
      ubiquitylation and degradation. We conclude that Tbetagamma is a substrate of the
      ubiquitin-proteasome pathway and suggest that phosducin serves to protect
      Tbetagamma following the light-dependent dissociation of Talphabetagamma.

PMID- 12215440
TI  - Charge attraction and beta propensity are necessary for amyloid fibril formation
      from tetrapeptides.
AB  - Amyloid fibrils in which specific proteins have polymerized into a cross-beta
      sheet structure are found in about 20 diseases. In contrast to the close
      structural similarity of fibrils formed in different amyloid diseases, the
      structures of the corresponding native proteins differ widely. We show here that
      peptides as short as 4 residues with the sequences KFFE or KVVE can form amyloid
      fibrils that are practically identical to fibrils formed in association with
      disease, as judged by electron microscopy and Congo red staining. In contrast,
      KLLE or KAAE do not form fibrils. The fibril-forming KFFE and KVVE show partial
      beta-strand conformation in solution, whereas the non-fibril-forming KLLE and
      KAAE show random structure only, suggesting that inherent propensity for beta
      strand conformation promotes fibril formation. The peptides KFFK or EFFE do not
      form fibrils on their own but do so in an equimolar mixture. Thus, intermolecular
      electrostatic interactions, either between charged dipolar peptides or between
      complementary charges of co-fibrillating peptides favor fibril formation.

PMID- 12215441
TI  - TH2 cytokines and allergic challenge induce Ym1 expression in macrophages by a
      STAT6-dependent mechanism.
AB  - The diverse functions of macrophages as participants in innate and acquired
      immune responses are regulated by the specific milieu of environmental factors,
      cytokines, and other signaling molecules that are encountered at sites of
      inflammation. Microarray analysis of the transcriptional response of mouse
      peritoneal macrophages to the T(H)2 cytokine interleukin-4 (IL-4) identified Ym1
      and arginase as the most highly up-regulated genes, exhibiting more than 68- and
      88-fold induction, respectively. Molecular characterization of the Ym1 promoter
      in transfected epithelial and macrophage cell lines revealed the presence of
      multiple signal transducers and activators of transcription 6 (STAT6) response
      elements that function in a combinatorial manner to mediate transcriptional
      responses to IL-4. The participation of STAT6 as an obligate component of protein
      complexes binding to these sites was established by analysis of nuclear extracts
      derived from STAT6-deficient macrophages. Macrophage expression of Ym1 was highly
      induced in vivo by an IL-4- and STAT6-dependent mechanism during the evolution of
      allergic peritonitis, supporting the biological relevance of the IL-4-dependent
      pathway characterized ex vivo in peritoneal macrophages. These studies establish
      Ym1 as a highly inducible STAT6-dependent transcript in T(H)2-biased inflammation
      and define Cis-active elements in the Ym1 promoter that are required for this
      transcriptional response.

PMID- 12215442
TI  - Binding of p190RhoGEF to a destabilizing element on the light neurofilament mRNA
      is competed by BC1 RNA.
AB  - The enhancement of RNA-mediated motor neuron degeneration in transgenic mice by
      mutating a major mRNA instability determinant in a light neurofilament (NF-L)
      transgene implicates cognate RNA binding factors in the pathogenesis of motor
      neuron degeneration. p190RhoGEF is a neuron-enriched guanine exchange factor
      (GEF) that binds to the NF-L-destabilizing element, to c-Jun N-terminal kinase
      interactive protein-1 (JIP-1), and to 14-3-3 and may link neurofilament
      expression to pathways affecting neuronal homeostasis. This study was undertaken
      to identify additional RNA species that bind p190RhoGEF and could affect
      interactions of the exchange factor with NF-L transcripts. The C-terminal domain
      of p190RhoGEF, containing the RNA-binding site, was expressed as a glutathione S
      transferase fusion protein and was used as an affinity probe to isolate
      interactive RNAs in rat brain extracts. As expected, NF-L mRNA was identified as
      an RNA specie eluted from the affinity column. In addition, BC1 RNA was also
      found enriched in the bound RNA fraction. BC1 is a 152-nucleotide RNA that is
      highly expressed but untranslated in differentiated neurons. We show that BC1 and
      NF-L mRNA bind to a similar site in the C-terminal domain of p190RhoGEF, and
      their bindings to p190RhoGEF are readily cross-competed. Moreover, we identify a
      novel binding site in BC1 to account for its interaction with p190RhoGEF. The
      findings suggest a novel role of BC1 in differentiated neurons involving RNA
      protein interactions of p190RhoGEF.

PMID- 12215443
TI  - Reversible unfolding of FtsZ cell division proteins from archaea and bacteria.
      Comparison with eukaryotic tubulin folding and assembly.
AB  - The stability, refolding, and assembly properties of FtsZ cell division proteins
      from Methanococcus jannaschii and Escherichia coli have been investigated. Their
      guanidinium chloride unfolding has been studied by circular dichroism
      spectroscopy. FtsZ from E. coli and tubulin released the bound guanine
      nucleotide, coinciding with an initial unfolding stage at low denaturant
      concentrations, followed by unfolding of the apoprotein. FtsZ from M. jannaschii
      released its nucleotide without any detectable secondary structural change. It
      unfolded in an apparently two-state transition at larger denaturant
      concentrations. Isolated FtsZ polypeptide chains were capable of spontaneous
      refolding and GTP-dependent assembly. The homologous eukaryotic tubulin monomers
      misfold in solution, but fold within the cytosolic chaperonin CCT. Analysis of
      the extensive tubulin loop insertions in the FtsZ/tubulin common core and of the
      intermolecular contacts in model microtubules and tubulin-CCT complexes shows a
      loop insertion present at every element of lateral protofilament contact and at
      every contact of tubulin with CCT (except at loop T7). The polymers formed by
      purified FtsZ have a distinct limited protofilament association in comparison
      with microtubules. We propose that the loop insertions of tubulin and its CCT
      assisted folding coevolved with the lateral association interfaces responsible
      for extended two-dimensional polymerization into microtubule polymers.

PMID- 12215444
TI  - EPR studies of the mitochondrial alternative oxidase. Evidence for a diiron
      carboxylate center.
AB  - The alternative oxidase (AOX) is a ubiquinol oxidase found in the mitochondrial
      respiratory chain of plants as well as some fungi and protists. It has been
      predicted to contain a coupled diiron center on the basis of a conserved sequence
      motif consisting of the proposed iron ligands, four glutamate and two histidine
      residues. However, this prediction has not been experimentally verified. Here we
      report the high level expression of the Arabidopsis thaliana alternative oxidase
      AOX1a as a maltose-binding protein fusion in Escherichia coli. Reduction and
      reoxidation of a sample of isolated E. coli membranes containing the alternative
      oxidase generated an EPR signal characteristic of a mixed-valent Fe(II)/Fe(III)
      binuclear iron center. The high anisotropy of the signal, the low value of the g
      average tensor, and a small exchange coupling (-J) suggest that the iron center
      is hydroxo-bridged. A reduced membrane preparation yielded a parallel mode EPR
      signal with a g-value of about 15. In AOX containing a mutation of a putative
      glutamate ligand of the diiron center (E222A or E273A) the EPR signals are
      absent. These data provide evidence for an antiferromagnetic-coupled binuclear
      iron center, and together with the conserved sequence motif, identify the
      alternative oxidase as belonging to the growing family of diiron carboxylate
      proteins. The alternative oxidase is the first integral membrane protein in this
      family, and adds a new catalytic activity (ubiquinol oxidation) to this group of
      enzymatically diverse proteins.

PMID- 12215445
TI  - Hypoxia-inducible factor 1 transactivates the human leptin gene promoter.
AB  - Increased placental leptin has been demonstrated in preeclampsia, a pregnancy
      disorder associated with placental hypoxia. This suggests that leptin gene
      expression is enhanced in response to oxygen deficiency in this organ. In support
      of this hypothesis, we have previously shown that hypoxia activates the leptin
      promoter in trophoblast-derived BeWo cells. Hypoxia-inducible factor 1 (HIF-1) is
      a heterodimeric HIF-1alpha/HIF-1beta complex that regulates the transcription of
      hypoxia-responsive genes. To test whether this factor is involved in hypoxia
      induced leptin promoter activation, BeWo cells were transiently transfected with
      a HIF-1alpha expression vector. Exogenous HIF-1alpha markedly increased
      luciferase reporter activity driven by the leptin promoter when HIF-1beta was co
      expressed in the same cells. This effect was similar to that elicited by CoCl2,
      an agent known to stabilize endogenous HIF-1alpha. These data suggest that HIF
      1alpha/HIF-1beta dimers are involved in the effect of CoCl2 to activate the
      leptin promoter. To confirm the implication of HIF-1, the cells were transfected
      with a dominant negative form of HIF-1alpha producing transcriptionally inactive
      HIF-1beta/HIF-1alpha dimers. This mutant HIF-1alpha protein abolished CoCl2
      activation of the leptin promoter, providing direct evidence that the effect of
      CoCl2 is mediated by endogenous HIF-1alpha. Deletion analysis and site-specific
      mutagenesis demonstrated that a HIF-1 consensus binding site (HRE) spanning -120
      to -116 bp relative to the start site was required for CoCl2 and exogenous HIF
      1alpha induction of leptin promoter activity. Electrophoretic mobility shift
      assays performed with in vitro-translated HIF-1alpha and HIF-1beta proteins
      demonstrated binding to this HRE and not to mutated sequences only when both
      subunits were used together. These data demonstrate that leptin is a new hypoxia
      inducible gene, which is stimulated in a placental cell line through HIF-1
      interaction with a consensus HRE site located at -116 in the proximal promoter.

PMID- 12215446
TI  - Mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 deficiency
      protects brain from ischemic injury in mice.
AB  - Mitogen-activated protein (MAP) kinase-activated protein kinase 2 (MK2) is one of
      several kinases directly regulated by p38 MAP kinase. A role of p38 MAP kinase in
      ischemic brain injury has been previously suggested by pharmacological means. In
      the present study, we provide evidence for a role of MK2 in cerebral ischemic
      injury using MK2-deficient (MK2(-/-)) mice. MK2(-/-) mice subjected to focal
      ischemia markedly reduced infarct size by 64 and 76% after transient and
      permanent ischemia, respectively, compared with wild-type mice. Furthermore, MK2(
      /-) mice had significant reduction in neurological deficits. Real-time PCR
      analysis identified a significantly lower expression in interleukin-1beta mRNA
      (53% reduction) but not in tumor necrosis factor-alpha mRNA in MK2(-/-) mice over
      wild-type animals after ischemic injury. The significant reduction in interleukin
      1beta was also confirmed in MK2(-/-) mice by enzyme-linked immunosorbent assay.
      The marked neuroprotection from ischemic brain injury in MK2(-/-) mice was not
      associated with the alteration of hemodynamic or systemic variables, activation
      of caspase-3, or apoptosis. Our data provide new evidence for the involvement of
      MAP kinase pathway in focal ischemic brain injury and suggest that this effect
      might be associated with the expression of interleukin-1beta in the ischemic
      brain tissue.

PMID- 12215448
TI  - Transition of arrestin into the active receptor-binding state requires an
      extended interdomain hinge.
AB  - Arrestins selectively bind to the phosphorylated activated form of G protein
      coupled receptors, thereby blocking further G protein activation. Structurally,
      arrestins consist of two domains topologically connected by a 12-residue long
      loop, which we term the "hinge" region. Both domains contain receptor-binding
      elements. The relative size and shape of arrestin and rhodopsin suggest that
      dramatic changes in arrestin conformation are required to bring all of its
      receptor-binding elements in contact with the cytoplasmic surface of the
      receptor. Here we use the visual arrestin/rhodopsin system to test the hypothesis
      that the transition of arrestin into its active receptor-binding state involves a
      movement of the two domains relative to each other that might be limited by the
      length of the hinge. We have introduced three insertions and 24 deletions in the
      hinge region and measured the binding of all of these mutants to light-activated
      phosphorylated (P-Rh*), dark phosphorylated (P-Rh), dark unphosphorylated (Rh),
      and light-activated unphosphorylated rhodopsin (Rh*). The addition of 1-3 extra
      residues to the hinge has no effect on arrestin function. In contrast, sequential
      elimination of 1-8 residues results in a progressive decrease in P-Rh* binding
      without changing arrestin selectivity for P-Rh*. These results suggest that there
      is a minimum length of the hinge region necessary for high affinity binding,
      consistent with the idea that the two domains move relative to each other in the
      process of arrestin transition into its active receptor-binding state. The same
      length of the hinge is also necessary for the binding of "constitutively active"
      arrestin mutants to P-Rh*, dark P-Rh, and Rh*, suggesting that the active
      (receptor-bound) arrestin conformation is essentially the same in both wild type
      and mutant forms.

PMID- 12215447
TI  - The long form of FLIP is an activator of caspase-8 at the Fas death-inducing
      signaling complex.
AB  - Death receptors, such as Fas and tumor necrosis factor-related apoptosis-inducing
      ligand receptors, recruit Fas-associated death domain and pro-caspase-8
      homodimers, which are then autoproteolytically activated. Active caspase-8 is
      released into the cytoplasm, where it cleaves various proteins including pro
      caspase-3, resulting in apoptosis. The cellular Fas-associated death domain-like
      interleukin-1-beta-converting enzyme-inhibitory protein long form (FLIP(L)), a
      structural homologue of caspase-8 lacking caspase activity because of several
      mutations in the active site, is a potent inhibitor of death receptor-induced
      apoptosis. FLIP(L) is proposed to block caspase-8 activity by forming a
      proteolytically inactive heterodimer with caspase-8. In contrast, we propose that
      FLIP(L)-bound caspase-8 is an active protease. Upon heterocomplex formation, a
      limited caspase-8 autoprocessing occurs resulting in the generation of the p43/41
      and the p12 subunits. This partially processed form but also the non-cleaved
      FLIP(L)-caspase-8 heterocomplex are proteolytically active because they both bind
      synthetic substrates efficiently. Moreover, FLIP(L) expression favors receptor
      interacting kinase (RIP) processing within the Fas-signaling complex. We propose
      that FLIP(L) inhibits caspase-8 release-dependent pro-apoptotic signals, whereas
      the single, membrane-restricted active site of the FLIP(L)-caspase-8
      heterocomplex is proteolytically active and acts on local substrates such as RIP.

PMID- 12215449
TI  - Sex-dependent thermogenesis, differences in mitochondrial morphology and
      function, and adrenergic response in brown adipose tissue.
AB  - Gender-related differences in brown adipose tissue (BAT) thermogenesis of 110-day
      old rats were studied by determining the morphological and functional features of
      BAT. The adrenergic control was assessed by studying the levels of beta(3)- and
      alpha(2A)-adrenergic receptors (AR) and by determining the lipolytic response to
      norepinephrine (beta(1)-, beta(2)-, beta(3)-, and alpha(2)-AR agonist),
      isoprenaline (beta(1)-, beta(2)-, and beta(3)-AR agonist), and CGP12177A
      (selective partial beta(3)-AR agonist but beta(1)- and beta(2)-AR antagonist)
      together with post-receptor agents, forskolin and dibutyryl cyclic AMP. The
      female rats that had greater oxygen consumption showed higher UCP1 content, a
      higher multilocular arrangement, and both longer cristae and higher cristae dense
      mitochondria in BAT indicating heightened thermogenic capacity and activity; this
      picture is accompanied by a more sensitive beta(3)-AR to norepinephrine signal
      (EC(50) 10-fold lower for CGP12177A) and a lower expression of alpha(2A)-AR than
      male rats. Taken together, our results support the idea that the BAT hormonal
      environment could be involved in the control of different elements of lipolytic
      and thermogenic adrenergic pathways. Gender dimorphism is both at receptor
      (changing alpha(2A)-AR density and beta(3)-AR affinity) and post-receptor
      (modulating the links involved in the adrenergic signal transduction) levels.
      These changes in adrenergic control could be responsible, at least in part, both
      for the important mitochondrial recruitment differences and functional and
      morphological features of BAT in female rats under usual rodent housing
      temperatures.

PMID- 12215450
TI  - Control of receptor-induced signaling complex formation by the kinetics of
      ligand/receptor interaction.
AB  - Tumor necrosis factor (TNF) exists both as a membrane-integrated type II
      precursor protein and a soluble cytokine that have different bioactivities on
      TNFR2 (CD120b) but not on TNFR1 (CD120a). To identify the molecular basis of this
      disparity, we have investigated receptor chimeras comprising the cytoplasmic part
      of Fas (CD95) and the extracellular domains of the two TNF receptors. The
      membrane form of TNF, but not its soluble form, was capable of inducing apoptosis
      as well as activation of c-Jun N-terminal kinase and NF-kappaB via the TNFR2
      derived chimera. In contrast, the TNFR1-Fas chimera displayed strong
      responsiveness to both TNF forms. This pattern of responsiveness is identical to
      that of wild type TNF receptors, demonstrating that the underlying mechanisms are
      independent of the particular type of the intracellular signaling machinery and
      rather are controlled upstream of the intracellular domain. We further
      demonstrate that the signaling strength induced by a given ligand/receptor
      interaction is regulated at the level of adaptor protein recruitment, as shown
      for FADD, caspase-8, and TRAF2. Since both incidents, strong signaling and robust
      adapter protein recruitment, are paralleled by a high stability of individual
      ligand-receptor complexes, we propose that half-lives of individual ligand
      receptor complexes control signaling at the level of adaptor protein recruitment.

PMID- 12215451
TI  - ABCA1-mediated cholesterol efflux is defective in free cholesterol-loaded
      macrophages. Mechanism involves enhanced ABCA1 degradation in a process requiring
      full NPC1 activity.
AB  - In advanced atherosclerosis, macrophage foam cells progressively accumulate large
      amounts of unesterified or "free" cholesterol (FC), a process that is thought to
      contribute to foam cell death and lesional necrosis. The cellular consequences of
      early FC accumulation, including those that lead to further FC accumulation, are
      poorly understood. In this context, we show that cholesterol and phospholipid
      efflux mediated by ABCA1, which is initially induced in the cholesterol-loaded
      macrophage, was inhibited by approximately 80% in pre-toxic FC-loaded
      macrophages. Cholesterol efflux to HDL(2), which is mediated by a non-ABCA1
      pathway, was inhibited by only approximately 20% in FC-loaded macrophages. FC
      loading led to decreased levels of ABCA1 protein via increased degradation of
      ABCA1, and not by decreased transcription or translation of AbcA1 mRNA. The
      decrease in ABCA1 protein occurred relatively early and was not prevented by
      caspase inhibitors, indicating that it was not a consequence of FC-induced
      apoptosis. However, inhibition of proteasomal function by lactacystin largely
      prevented the degradation of ABCA1. Importantly, the FC-induced decrease in ABCA1
      function and protein was almost entirely prevented in macrophages that had
      partial deficiency of npc1 or were exposed to nanomolar concentrations of
      U18666A, both of which lead to defective cholesterol trafficking to the
      endoplasmic reticulum, but leave trafficking to the plasma membrane largely
      intact. Thus, a relatively early event during FC loading of macrophages is
      increased degradation of ABCA1, which appears to require trafficking of
      cholesterol to a peripheral cellular site, but not bulk trafficking of excess
      cholesterol to the plasma membrane. These findings provide new insight into the
      post-translational regulation of ABCA1 and the pathobiology of the FC-loaded
      macrophage.

PMID- 12215452
TI  - Mechanisms regulating expression of the tumor necrosis factor-related light gene.
      Role of calcium-signaling pathway in the transcriptional control.
AB  - LIGHT (TNFSF14) is a newly identified tumor necrosis factor superfamily member
      involved in the regulation of immune responses by control of activation,
      maturation, and survival of immune effector cells. Despite the immunological
      relevance of the LIGHT protein, little knowledge is available as to how light
      gene expression is regulated. In T-lymphocytes, most LIGHT surface expression and
      transcript accumulation occurs after T cell activation. In this study, we have
      shown that these events are blocked at the transcriptional level by cyclosporin
      A, an immuno-suppressive drug. Besides, we identified a role for Ca2+ -signaling
      pathways and NFAT transcription factors in T cell activation-induced LIGHT
      expression. To further investigate this process, we have identified, cloned, and
      characterized a 2.1-kilobase 5'-flanking DNA genomic fragment from the human
      light gene. We have shown the transcriptional activity of the herein-identified
      minimal 5' regulatory region of human light gene parallels the endogenous
      expression of light in T cells. Moreover, we demonstrated that induced LIGHT
      promoter activity can be equally blocked by cyclosporin A treatment or dominant
      negative NFAT overexpression and further identified by site-directed mutagenesis
      and electrophoretic mobility supershift analysis of a NFAT transcription factor
      binding site within the human light minimal promoter. Finally, Sp1 and Ets1
      binding sites were identified and shown to regulate light basal promoter
      activity. Thus, the present study establishes a molecular basis to further
      understand the mechanisms governing human light gene expression and,
      consequently, could potentially lead to novel therapeutic manipulations that
      control the signaling cascade, resulting in LIGHT production in conditions
      characterized by immunopathologic activation of T cells.

PMID- 12215453
TI  - Biochemical characterization of a membrane-bound manganese-containing superoxide
      dismutase from the cyanobacterium Anabaena PCC 7120.
AB  - The filamentous cyanobacterium Anabaena PCC 7120 (now renamed Nostoc PCC 7120)
      possesses two genes for superoxide dismutase (SOD). One is an iron-containing
      (FeSOD) whereas the other is a manganese-containing superoxide dismutase (MnSOD).
      Localization experiments and analysis of the sequence showed that the FeSOD is
      cytosolic, whereas the MnSOD is a membrane-bound homodimeric protein containing
      one transmembrane helix, a spacer region, and a soluble catalytic domain. It is
      localized in both cytoplasmic and thylakoid membranes at the same extent with the
      catalytic domains positioned either in the periplasm or the thylakoid lumen. A
      phylogenetic analysis revealed that generally the highly homologous MnSODs of
      filamentous cyanobacteria are unique in being membrane-bound. Two recombinant
      variants of Anabaena MnSOD lacking either the hydrophobic region (MnSOD(Delta
      28)) or the hydrophobic and the linker region (MnSOD(Delta 60)) are shown to
      exhibit the characteristic manganese peak at 480 nm, an almost 100% occupancy of
      manganese per subunit, a specific activity using the ferricytochrome assay of
      (660 +/- 90) unit mg-1 protein and a dissociation constant for the inhibitor
      azide of (0.84 +/- 0.05) mm. Using stopped-flow spectroscopy it is shown that the
      decay of superoxide in the presence of various (MnSOD(Delta 28)) or (MnSOD(Delta
      60)) concentrations is first-order in enzyme concentration allowing the
      calculation of catalytic rate constants which increase with decreasing pH: 8 x
      10(6) m-1 s-1 (pH 10) and 6 x 10(7) m-1 s-1 (pH 7). The physiological relevance
      of these findings is discussed with respect to the bioenergetic peculiarities of
      cyanobacteria.

PMID- 12215454
TI  - Formation and decay of hydroperoxo-ferric heme complex in horseradish peroxidase
      studied by cryoradiolysis.
AB  - Using radiolytic reduction of the oxy-ferrous horseradish peroxidase (HRP) at 77
      K, we observed the formation and decay of the putative intermediate, the
      hydroperoxo-ferric heme complex, often called "Compound 0." This intermediate is
      common for several different enzyme systems as the precursor of the Compound I
      (ferryl-oxo pi-cation radical) intermediate. EPR and UV-visible absorption
      spectra show that protonation of the primary intermediate of radiolytic
      reduction, the peroxo-ferric complex, to form the hydroperoxo-ferric complex is
      completed only after annealing at temperatures 150-180 K. After further annealing
      at 195-205 K, this complex directly transforms to ferric HRP without any
      observable intervening species. The lack of Compound I formation is explained by
      inability of the enzyme to deliver the second proton to the distal oxygen atom of
      hydroperoxide ligand, shown to be necessary for dioxygen bond heterolysis on the
      "oxidase pathway," which is non-physiological for HRP. Alternatively, the
      physiological substrate H2O2 brings both protons to the active site of HRP, and
      Compound I is subsequently formed via rearrangement of the proton from the
      proximal to the distal oxygen atom of the bound peroxide.

PMID- 12215455
TI  - Barrier to autointegration factor interacts with the cone-rod homeobox and
      represses its transactivation function.
AB  - Crx (cone-rod homeobox) is a homeodomain transcription factor implicated in
      regulating the expression of photoreceptor and pineal genes. To identify proteins
      that interact with Crx in the retina, we carried out a yeast two-hybrid screen of
      a retinal cDNA library. One of the identified clones encodes Baf (barrier to
      autointegration factor), which was previously shown to have a role in mitosis and
      retroviral integration. Additional biochemical assays provided supporting
      evidence for a Baf-Crx interaction. The Baf protein is detectable in all nuclear
      layers of the mouse retina, including the photoreceptors and the bipolar cells
      where Crx is expressed. Transient transfection assays with a rhodopsin-luciferase
      reporter in HEK293 cells demonstrate that overexpression of Baf represses Crx
      mediated transactivation, suggesting that Baf acts as a negative regulator of
      Crx. Consistent with this role for Baf, an E80A mutation of CRX associated with
      cone-rod dystrophy has a higher than normal transactivation potency but a reduced
      interaction with Baf. Although our studies did not identify a causative Baf
      mutation in retinopathies, we suggest that Baf may contribute to the phenotype of
      a photoreceptor degenerative disease by modifying the activity of Crx. In view of
      the ubiquitous expression of Baf, we hypothesize that it may play a role in
      regulating tissue- or cell type-specific gene expression by interacting with
      homeodomain transcription factors.

PMID- 12215456
TI  - CD3 delta establishes a functional link between the T cell receptor and CD8.
AB  - T cells expressing T cell receptor (TCR) complexes that lack CD3 delta, either
      due to deletion of the CD3 delta gene, or by replacement of the connecting
      peptide of the TCR alpha chain, exhibit severely impaired positive selection and
      TCR-mediated activation of CD8 single-positive T cells. Because the same defects
      have been observed in mice expressing no CD8 beta or tailless CD8 beta, we
      examined whether CD3 delta serves to couple TCR.CD3 with CD8. To this end we used
      T cell hybridomas and transgenic mice expressing the T1 TCR, which recognizes a
      photoreactive derivative of the PbCS 252-260 peptide in the context of H-2K(d).
      We report that, in thymocytes and hybridomas expressing the T1 TCR.CD3 complex,
      CD8 alpha beta associates with the TCR. This association was not observed on T1
      hybridomas expressing only CD8 alpha alpha or a CD3 delta(-) variant of the T1
      TCR. CD3 delta was selectively co-immunoprecipitated with anti-CD8 antibodies,
      indicating an avid association of CD8 with CD3 delta. Because CD8 alpha beta is a
      raft constituent, due to this association a fraction of TCR.CD3 is raft
      associated. Cross-linking of these TCR-CD8 adducts results in extensive TCR
      aggregate formation and intracellular calcium mobilization. Thus, CD3 delta
      couples TCR.CD3 with raft-associated CD8, which is required for effective
      activation and positive selection of CD8(+) T cells.

PMID- 12215457
TI  - Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor
      gene reveals an essential role of IGF signaling in bone matrix mineralization.
AB  - To examine the local actions of IGF signaling in skeletal tissue in a
      physiological context, we have used Cre-mediated recombination to disrupt
      selectively in mouse osteoblasts the gene encoding the type 1 IGF receptor
      (Igf1r). Mice carrying this bone-specific mutation were of normal size and weight
      but, in comparison with normal siblings, demonstrated a striking decrease in
      cancellous bone volume, connectivity, and trabecular number, and an increase in
      trabecular spacing. These abnormalities correlated with a striking decrease in
      the rate of mineralization of osteoid that occurred despite an unexpected
      osteoblast and osteoclast hyperactivity, detected from the significant increments
      in both osteoblast and erosion surfaces. Our findings indicate that IGF1 is
      essential for coupling matrix biosynthesis to sustained mineralization. This
      action is likely to be particularly important during the pubertal growth spurt
      when rapid bone formation and consolidation are required.

PMID- 12215458
TI  - Chronology versus biology: telomeres, essential hypertension, and vascular aging.
AB  - There is considerable evidence that essential hypertension is closely linked to
      the growth, development, and aging of human beings. It is imperative, therefore,
      to introduce biological indicators of growth and aging into models developed to
      provide a better understanding of the etiology of essential hypertension. One of
      these indicators may well be the age-dependent telomere attrition rate in somatic
      cells. Telomere attrition registers the replicative history of somatic cells. As
      such, it chronicles not only the growth that results from the replication of
      somatic cells but also their turnover-a process that is strongly linked to
      inflammation and oxidative stress, which are key factors in the biology of human
      aging.

PMID- 12215459
TI  - Sibling resemblance for left ventricular structure, contractility, and diastolic
      filling.
AB  - Although there is evidence that left ventricular (LV) function is genetically
      controlled, the contribution of familial factors to variation and covariation of
      LV diastolic filling, contractility, and structure is unknown. Single- and cross
      trait sibling correlations were estimated using bivariate familial correlation
      models in 200 white (400 pairs) and 374 black (539 pairs) hypertensive sibships.
      LV transmitral early and late peak filling velocities, isovolumic relaxation
      time, atrial filling fraction, stress-corrected midwall shortening, and LV mass
      and structure were measured and adjusted for important covariates in race
      specific linear regression models. Single-trait sibling correlation was strongest
      for early peak filling velocity. Significant cross-trait sibling correlation was
      detected between early and late peak filling velocities. In whites, early peak
      filling velocity and atrial filling fraction, and isovolumic relaxation time and
      end-diastolic posterior wall thickness, were also significantly correlated.
      Familial factors common to early and late peak filling velocities contributed to
      64% and 54% of sibling resemblance in early peak filling velocity and to 76% and
      77% in late peak filling velocity in blacks and whites, respectively. In whites,
      100% of sibling resemblance in isovolumic relaxation time was shared by posterior
      wall thickness, whereas 75% of sibling influence in posterior wall thickness was
      common to isovolumic relaxation time. In conclusion, significant cross-trait
      sibling resemblance was detected between (1) early and late filling parameters
      and (2) isovolumic relaxation time and posterior wall thickness, suggesting
      pleiotropy and/or common environment on these traits. These data have potential
      importance in understanding heritability of LV diastolic function in
      hypertension.

PMID- 12215460
TI  - Ultrasonic backscatter and diastolic function in hypertensive patients.
AB  - This study was designed to assess whether ultrasonic reflectivity, evaluated by a
      real-time integrated backscatter analysis, was related to the severity of
      diastolic dysfunction, as studied by Doppler echocardiography in patients with
      essential hypertension. One hundred nine subjects were included in the study.
      Diastolic function was assessed by mitral-inflow Doppler ultrasound recordings.
      Backscatter cyclic variation and maximal intensity were measured in 6 regions
      throughout the left ventricle. The subjects were classified in 5 groups according
      to blood pressure and diastolic function: 29 normotensives with normal diastolic
      function (group 1), 18 hypertensives with normal diastolic function (group 2), 47
      hypertensives with a delayed relaxation pattern (group 3), 11 hypertensives with
      a pseudonormal filling pattern (group 4), and 4 hypertensives with a restrictive
      filling pattern (group 5). The highest cyclic variation was found in groups 1 and
      2, the lowest in groups 4 and 5 (5.7+/-0.2 dB in group 1 and 5.7+/-0.2 dB in
      group 2 versus 2.9+/-0.3 dB in group 4 and 2.1+/-0.4 dB in group 5; P<0.001),
      with intermediate values in group 3 (5.2+/-0.2 dB). Cyclic variation was
      inversely correlated with left ventricular chamber stiffness (P<0.05) and
      directly correlated with midwall fractional shortening (P<0.02) in all
      hypertensives. No differences in maximal intensity were found among the 5 groups
      of subjects. These results show an association between diminished cyclic
      variation of backscatter and deterioration of diastolic function in hypertensive
      patients. Thus, alterations in this parameter may be useful for the assessment of
      diastolic dysfunction in hypertension.

PMID- 12215461
TI  - Role of AT2 receptors in the cardioprotective effect of AT1 antagonists in mice.
AB  - Angiotensin II (Ang II) acts mainly on two receptor subtypes: AT1 and AT2. Most
      of the known biological actions of Ang II are mediated by AT1 receptors; however,
      the role of AT2 receptors remains unclear. We tested the hypothesis that the
      cardioprotective effects of AT1 receptor antagonists (AT1-ant) after myocardial
      infarction (MI) are partially mediated by activation of AT2 receptors; thus in
      AT2 receptor gene knockout mice (AT2-/Y), the effect of AT1-ant will be
      diminished or absent. MI was induced by ligating the left anterior descending
      coronary artery. Four weeks later, AT2-/Y and their wild-type littermates
      (AT2+/Y) were started on vehicle, AT1-ant (valsartan, 50 mg/kg per day), or ACE
      inhibitor (enalapril, 20 mg/kg per day) for 20 weeks. Basal blood pressure and
      cardiac function as well as remodeling after MI did not differ between AT2+/Y and
      AT2-/Y. AT1-ant increased ejection fraction and cardiac output and decreased left
      ventricular diastolic dimension, myocyte cross-sectional area, and interstitial
      collagen deposition in AT2+/Y, and these effects were significantly diminished in
      AT2-/Y. ACE inhibitors improved cardiac function and remodeling similarly in both
      strains. We concluded that (1) activation of AT2 during AT1 blockade plays an
      important role in the therapeutic effect of AT1-ant and (2) the AT2 receptor may
      not play an important role in regulation of cardiac function, either under basal
      conditions after MI remodeling or in the therapeutic effect of ACE inhibitors.

PMID- 12215462
TI  - Perindopril effect on uncoupling protein and energy metabolism in failing rat
      hearts.
AB  - Uncoupling proteins, inner mitochondrial membrane proton transporters, are
      important for regulating myocardial energy efficiency. We investigated the
      effects of the ACE inhibitor perindopril on cardiac performance, myocardial
      energy efficiency, and uncoupling protein expression in an aortic regurgitation
      rat model. Twenty male Sprague-Dawley rats, in which aortic regurgitation was
      produced, were divided into untreated and perindopril-treated (5 mg x kg(-1) x d(
      1)) rats. The treatments were initiated 3 days after operation. Ten control rats
      were sham-operated. Measurements of blood pressure and echocardiography were
      repeated before and 100 days after operation (endpoint). Left ventricular
      uncoupling protein-2 expression, creatine phosphate, and adenosine triphosphate
      were measured at endpoint. In perindopril-treated rats, systolic and diastolic
      blood pressure decreased after treatment (92+/-4/65+/-2 mm Hg). At endpoint, left
      ventricular end-diastolic dimension in untreated (10.7+/-0.2 mm) and treated rats
      (9.2+/-0.2 mm) was increased, and fractional shortening was reduced in untreated
      rats (28+/-1%) but did not change in treated rats (36+/-2%). Uncoupling protein-2
      mRNA expression increased in untreated rats (3.7-fold) and was suppressed by
      perindopril (1.5-fold). The creatine phosphate was reduced in untreated rats
      (10.6+/-0.7 micro mol/g) but not in treated rats (15.9+/-2.0 micro mol/g). In the
      chronic stage of aortic regurgitation, perindopril improved cardiac performance
      and myocardial energy efficiency, in which the suppression of uncoupling protein
      2 may play an important role.

PMID- 12215464
TI  - Association of GNAS1 gene variant with hypertension depending on smoking status.
AB  - The beta-adrenoceptor (beta-AR) G(s) protein system has been shown to have
      important roles in the cardiovascular system. The gene encoding the alpha-subunit
      of G(s) proteins (GNAS1) is a candidate genetic determinant for hypertension. We
      studied the GNAS1 T393C polymorphism in >2000 Japanese individuals. chi(2) test
      showed a marginally significant difference in the frequencies of the alleles
      (P=0.036) and genotypes (P=0.094) between hypertensives and normotensives.
      Because hypertension is considered to be a complex disorder resulting from
      interactions between genetic and environmental factors, we further analyzed the
      T393C polymorphism, with consideration of interactions between the polymorphism
      and confounding factors in regression models. These analyses showed a significant
      interaction between the polymorphism and cigarette smoking in the pathogenesis of
      hypertension (P=0.0005). The interaction was reflected in a significant
      association of the polymorphism with hypertension in nonheavy smokers (P=0.0028;
      odds ratio, 1.52; 95% confidence interval, 1.16 to 2.00). A significant
      interaction between the polymorphism and aging in the pathogenesis of
      hypertension was also shown in nonheavy smokers. These findings may be helpful in
      conducting further molecular and biological studies on the relationship among
      cigarette smoking, the beta-AR-G(s) protein system, and hypertension.

PMID- 12215463
TI  - Serum- and glucocorticoid-regulated kinase (SGK1) gene and blood pressure.
AB  - The serum- and glucose-regulated kinase (SGK1) gene has recently been identified
      as an important aldosterone-induced protein kinase that mediates trafficking of
      the renal epithelial Na(+) channel (ENaC) to the cell membrane. Thus, SGK1 is an
      appealing candidate for blood pressure regulation and possibly essential
      hypertension. To test this hypothesis, we recruited monozygotic (126 pairs) and
      dizygotic (70 pairs) normotensive twin subjects and parents of dizygotic twins.
      Blood pressure was measured in a controlled fashion: recumbent, sitting, and
      upright. We documented genetic variance on blood pressure in all positions. We
      then relied on microsatellite markers at the SGK1 gene locus (D6S472, D6S1038,
      and D6S270) and 2 single nucleotide polymorphisms within the SGK1 gene. We found
      significant linkage of the SGK1 gene locus to diastolic blood pressure (P<0.0002)
      and suggestive evidence for linkage for systolic blood pressure (P<0.04),
      documenting the locus as a quantitative trait locus for blood pressure. We next
      performed association, using all dizygotic twins and a monozygotic member from
      each pair. We found significant associations between both single nucleotide
      polymorphism variants and blood pressure, as well as a significant interaction
      between the single nucleotide polymorphisms enhancing the effect. This combined
      effect of the polymorphisms was confirmed in an independent sample of 260 young
      normotensive men. We conclude that the SGK1 gene is relevant to blood pressure
      regulation and probably to hypertension in man.

PMID- 12215465
TI  - Renal hemodynamic and natriuretic effects of concomitant Angiotensin-converting
      enzyme and neutral endopeptidase inhibition in men.
AB  - This double-blind placebo-controlled study was designed to investigate the acute
      and sustained hormonal, renal hemodynamic, and tubular effects of concomitant ACE
      and neutral endopeptidase (NEP) inhibition by omapatrilat, a vasopeptidase
      inhibitor, in men. Thirty-two normotensive subjects were randomized to receive a
      placebo, omapatrilat (40 or 80 mg), or the fosinopril/hydrochlorothiazide
      (FOS/HCTZ; 20 and 12.5 mg, respectively) fixed combination for 1 week. Blood
      pressure, renal hemodynamics, urinary electrolytes and atrial natriuretic peptide
      excretion, and several components of the renin-angiotensin system were measured
      for 6 hours on days 1 and 7 of drug administration. When compared with the
      placebo and the FOS/HCTZ combination, omapatrilat induced a significant decrease
      in plasma angiotensin II levels (P<0.001 versus placebo; P<0.05 versus FOS/HCTZ)
      and an increase in urinary atrial natriuretic peptide excretion (P<0.01). These
      hormonal effects were associated with a significant fall in blood pressure
      (P<0.01) and a marked renal vasodilatation, but with no significant changes in
      glomerular filtration rate. The FOS/HCTZ markedly increased urinary sodium
      excretion (P<0.001). The acute natriuretic response to FOS/HCTZ was significantly
      greater than that observed with omapatrilat (P<0.01). Over 1 week, however, the
      cumulative sodium excretion induced by both doses of omapatrilat (P<0.01 versus
      placebo) was at least as great as that induced by the dose of FOS/HCTZ (P=NS
      versus FOS/HCTZ). In conclusion, the results of the present study in normal
      subjects demonstrate that omapatrilat has favorable renal hemodynamic effects.
      Omapatrilat combines potent ACE inhibition with a sustained natriuresis, which
      explains its well-documented potent antihypertensive efficacy.

PMID- 12215466
TI  - P450-dependent arachidonic acid metabolism and angiotensin II-induced renal
      damage.
AB  - Transgenic rats overexpressing both human renin and angiotensinogen genes (dTGR)
      develop hypertension, inflammation, and renal failure. We tested the hypothesis
      that these pathological features are associated with changes in renal P450
      dependent arachidonic acid (AA) metabolism. Samples were prepared from 5- and 7
      week-old dTGR and from normotensive Sprague-Dawley (SD) rats, ie, before and
      after the dTGR developed severe hypertension and albuminuria. At both stages,
      dTGR showed significantly lower renal microsomal AA epoxygenase and hydroxylase
      activities that reached 63% and 76% of the control values at week 7. Furthermore,
      the protein levels of several potential AA epoxygenases (CYP2C11, CYP2C23, and
      CYP2J) were significantly reduced. Immunoinhibition studies identified CYP2C23 as
      the major AA epoxygenase, both in dTGR and SD rats. Immunohistochemistry showed
      that CYP2C23 was localized in cortical and outer medullary tubules that
      progressively lost this enzyme from week 5 to week 7 in dTGR. CYP2C11 expression
      occurred only in the outer medullary tubules and was markedly reduced in dTGR
      compared with age-matched SD rats. These findings indicate site-specific
      decreases in the availability of AA epoxygenase products in the kidney of dTGR.
      In contrast to renal microsomes, liver microsomes of dTGR and SD rats showed no
      change in the expression and activity of AA epoxygenases and hydroxylases. We
      conclude that hypertension and end-organ damage in dTGR is associated with kidney
      specific downregulation of P450-dependent AA metabolism. Because the products of
      AA epoxygenation have anti-inflammatory properties, this alteration may
      contribute to uncontrolled renal inflammation, which is a major cause of renal
      damage in dTGR.

PMID- 12215467
TI  - Neonatal blood pressure and salt taste responsiveness.
AB  - To test the association between neonatal blood pressure (BP) and salt taste
      response, 283 healthy hospitalized neonates were administered small drops (0.06
      mL) of water and 0.1 molar (mol/L) and 0.3 mol/L NaCl solutions by means of
      cannulas through a nipple with a pressure transducer to record sucking responses.
      Neonatal and 1-month BPs were recorded by ultrasound. Mean number of sucks per
      burst was scored as "aversive" if the 0.3 mol/L salt minus water difference score
      was < or =-10 mean sucks per burst, "preferential" if this difference was >0, and
      "neutral" otherwise. Babies with "preferential" responses had higher diastolic
      BPs than those with neutral (1.9 mm Hg) or aversive responses (3.1 mm Hg) (P
      trend=0.05). After adjustment for age, gender, birth weight, and activity for
      babies with at least one grandparent receiving antihypertensive medication, mean
      adjusted systolic pressure was 6.7 mm Hg higher (P=0.003) (P trend=0.003) and
      mean adjusted diastolic pressure was 5.0 mm Hg higher (P=0.010) (P trend=0.011)
      in neonates with preferential versus aversive salt taste responses. There was no
      relation of BP to sucking responses to sweet (sucrose) stimuli. Neonates can
      distinguish between dilute salt solutions and water. This response is related to
      BP and might be a potential risk factor for high BP later in life.

PMID- 12215468
TI  - Essential hypertension and beta2-adrenergic receptor gene: linkage and
      association analysis.
AB  - A region on human chromosome 5 (5q31.1-qter) contains several genes that encode
      important blood pressure regulators and thus is a good candidate for analysis of
      linkage and association with hypertension. We recruited 638 individuals from 212
      Polish pedigrees with clustering of essential hypertension. These subjects were
      genotyped for 11 microsatellite markers that span this region to test for linkage
      to essential hypertension and systolic and diastolic blood pressures. The segment
      of this region of approximately 7 cM delineated by D5S1480 and D5S500 markers was
      linked to blood pressures in multipoint analysis. In 2-point analysis, D5S1480-
      the marker in close proximity to beta2-adrenergic receptor gene--reached the
      maximal linkage to essential hypertension and adjusted systolic and diastolic
      blood pressures, implicating this gene as a positional candidate for further
      association studies. Arg16Gly, Gln27Glu, and Thr164Ile--3 functional single
      nucleotide polymorphisms within the beta2-adrenergic receptor gene--were tested
      for association with essential hypertension. None of these polymorphisms showed a
      significant association with essential hypertension, separately or in the
      haplotype analysis. This study provided evidence of linkage of 5q31.1-5qter
      region to essential hypertension in the European population. Moreover, it
      implicated the chromosomal segment in close proximity to D5S1480 and D5S500. The
      detailed analysis of 3 single nucleotide polymorphisms does not support the role
      of the beta2-adrenergic receptor gene as a major causative gene for the detected
      linkage.

PMID- 12215469
TI  - Kidney specificity of rat chromosome 1 blood pressure quantitative trait locus
      region.
AB  - Rat chromosome 1 has a region containing loci that influence blood pressure. In
      the present study, we investigated whether these loci mediate their effect via
      the kidney. Taking advantage of the histocompatibility between a congenic strain
      (WKY.SHR-Sa, which contains the relevant chromosomal region from the
      spontaneously hypertensive rat) and its parental strain, the Wistar-Kyoto rat
      (WKY), we compared the effect of transplanting a kidney at 5 to 6 weeks of age
      from either congenic rats or WKY into bilaterally nephrectomized WKY. WKY.SHR-Sa
      animals and WKY with intact kidneys and with unilateral nephrectomy were studied
      as controls. Blood pressure was measured at 12, 16, 20, and 25 weeks of age. At
      all time points, blood pressure was significantly higher (by between 8 to 22 mm
      Hg, P<0.001) in 2-kidney WKY.SHR-Sa animals compared with WKY. This genotype
      related difference was maintained in unilaterally nephrectomized rats. Most
      importantly, WKY that received transplants from WKY.SHR-Sa rats had significantly
      higher blood pressure (P<0.001 at all time points) compared with those that
      received transplants from other WKY. At any age, this difference was between 70%
      to 100% of the difference observed between the 1-kidney groups. There was no
      difference in plasma urea or creatinine between groups or evidence of chronic
      rejection in the cross-transplant group. The findings indicate that the major
      proportion of the blood pressure effect of loci on rat chromosome 1 is mediated
      through the kidney, and provide a rational basis for investigating genes located
      in the relevant chromosomal region and expressed in the kidney as likely
      candidates.

PMID- 12215470
TI  - Prognostic value of office and ambulatory blood pressure measurements in
      pregnancy.
AB  - With the objective to assess the prognostic value of office values as compared
      with ambulatory monitoring in pregnancy, we analyzed 2430 blood pressure series
      systematically sampled from 403 untreated pregnant women for 48 consecutive hours
      every 4 weeks from the first visit to the hospital until delivery. Women were
      divided into 5 groups: "detected" gestational hypertension, women with office
      blood pressures >140/90 mm Hg after 20 weeks of gestation and hyperbaric index
      (area of blood pressure excess above the upper limit of a time-specified
      tolerance interval) consistently above the threshold for diagnosing hypertension
      in pregnancy; "undetected" gestational hypertension, office values <140/90 mm Hg
      but hyperbaric index above the threshold for diagnosis; normotension, both office
      values and hyperbaric index below the thresholds for diagnosis; white coat
      hypertension, women with recorded diagnosis of gestational hypertension but
      hyperbaric index consistently below the threshold for diagnosis; and
      preeclampsia, defined as gestational hypertension and proteinuria. Results
      indicate small and nonsignificant differences in 24-hour mean of ambulatory
      pressures between "detected" and "undetected" gestational hypertension at all
      stages of pregnancy, in contrast with highly significant differences between
      these two groups and normotensive pregnancies. Average office blood pressure
      values were similar for preeclampsia, "detected," and "undetected" gestational
      hypertension. The hyperbaric index was, however, significantly higher for women
      with preeclampsia after 20 weeks of gestation as compared with all other groups
      and higher for women with either "detected" or "undetected" gestational
      hypertension as compared with normotensive pregnant women. The incidence of
      preterm delivery and intrauterine growth retardation were similar for "detected"
      and "undetected" gestational hypertension but significantly lower for
      normotensive women. In pregnancy, the hyperbaric index derived from ambulatory
      monitoring is markedly superior to office measurements for diagnosis of what
      should be truly considered gestational hypertension, as well as for prediction of
      the outcome of pregnancy.

PMID- 12215471
TI  - Noninvasive study of endothelial function in white coat hypertension.
AB  - Several studies have demonstrated that endothelial dysfunction is present in
      patients with essential hypertension. However, the presence of endothelial
      dysfunction in patients with white coat hypertension has not been studied. We
      evaluated the variation in the diameter of the brachial artery produced by flow
      mediated dilation after a mechanical stimulus in patients with recently diagnosed
      mild to moderate sustained essential hypertension compared with patients with
      white coat hypertension. A total of 29 patients fulfilled inclusion criteria; 15
      healthy volunteers were also included. After 24-hour ambulatory blood pressure
      monitoring, 15 patients were classified with sustained essential hypertension; 14
      patients with white coat hypertension. Vascular ultrasound scans were performed
      according to the method described by Celermajer et al, with modification for
      noninvasive determination of endothelial dysfunction. Basal brachial artery
      diameter did not differ significantly among the 3 groups. Changes in arterial
      diameter 60 seconds after cuff deflation were higher in the control group
      compared with both hypertensive groups, but no significant differences were found
      between the sustained essential hypertension group and the white coat
      hypertension group. Flow-mediated dilation was similar in white coat
      hypertensives and sustained essential hypertensives. The presence of endothelial
      dysfunction in subjects with white coat hypertension suggests that it should not
      be considered a harmless trait and that white coat hypertension has common
      features with sustained essential hypertension.

PMID- 12215472
TI  - Mitogenic activity of oxidized lipoprotein (a) on human vascular smooth muscle
      cells.
AB  - Although oxidized lipoproteins may play an important role in the progression of
      atherosclerosis, no report has mentioned the significance of oxidized lipoprotein
      (a) (Lp[a]) in the pathogenesis of cardiovascular disease. Initially, we compared
      the mitogenic actions of Lp(a) and oxidized Lp(a) on human vascular smooth muscle
      cells (VSMC). Lp(a) significantly stimulated the growth of human VSMC in a dose
      dependent manner, whereas oxidized Lp(a) showed a stronger stimulatory action on
      VSMC growth than native Lp(a). Interestingly, antioxidants probucol and
      fluvastatin inhibited the oxidation of Lp(a). Moreover, the stimulatory effect of
      oxidized Lp(a) on human VSMC growth was significantly inhibited by probucol.
      Finally, we elucidated the molecular mechanisms of how Lp(a) stimulated the
      growth of VSMC. Extracellular signal-regulated kinase (ERK), as those controlled
      by kinases, modulate critical cellular functions such as cell growth,
      differentiation, and apoptosis, was transiently phosphorylated by oxidized Lp(a)
      as well as native Lp(a) from 5 minutes, and the phosphorylation disappeared
      within 30 minutes. The degree of ERK phosphorylation by oxidized Lp(a) was much
      higher than that by native Lp(a). Administration of a specific inhibitor of MEK,
      PD 98059, significantly attenuated VSMC growth induced by native Lp(a) or
      oxidized Lp(a) in a dose-dependent manner (P<0.01). The current study
      demonstrated that oxidized Lp(a) is more potent than native Lp(a) in stimulating
      VSMC growth. Oxidized Lp(a) may play an important role in the pathogenesis of
      vascular disease.

PMID- 12215473
TI  - Selective regulation of blood pressure by heme oxygenase-1 in hypertension.
AB  - Heme oxygenase (HO) and carbon monoxide (CO) participate in the homeostatic
      control of cardiovascular functions, including the regulation of blood pressure
      (BP). Upregulation of the HO/CO system has been shown to lower BP in young (8
      weeks) but not in adult (20 weeks) spontaneously hypertensive rats (SHR). The
      underlying mechanism for this selective effect, however, has been unknown and was
      investigated in the present study. The administration of hemin resulted in a
      marked decrease in BP (from 148.6+/-3.2 to 125.8+/-2.6 mm Hg, P<0.01) in young
      but not in prehypertensive (4 weeks) or adult SHR or Wistar-Kyoto rats at all
      ages. The inhibition of HO with chromium mesoporphyrin abrogated the BP-lowering
      effect of hemin. Significantly lower expression levels of HO-1 and soluble
      gyanylyl cyclase (sGC) as well as reduced cGMP content were detected in 8-week
      SHR but not in adult SHR or Wistar-Kyoto rats of all ages. These deficiencies
      were all corrected by hemin treatment. The expression of HO-2 protein was not
      different among all animal groups tested and not affected by hemin treatment.
      Desensitization of the sGC/cGMP pathway in adult SHR was demonstrated by the
      reduced vasorelaxant potency of the sGC activator 3-(5' -hydroxymethyl-2-'furyl)
      1-benzylindazole. Thus, in young and prehypertensive SHR, a defective HO/CO
      sGC/cGMP system might constitute a pathogenic mechanism for the development of
      hypertension. The HO/CO-sGC/cGMP system appears normal in adult SHR, but
      desensitization of the downstream targets of the system to sGC/cGMP may endow SHR
      at this stage a persistent hypertension status.

PMID- 12215474
TI  - Vascular responses in male and female hypertensive rats with
      hyperhomocysteinemia.
AB  - We studied vascular responses in spontaneously hypertensive rats (SHR) of both
      genders after methionine (Met) loading to test whether or not there were gender
      differences. SHRs were divided into 5 groups: male control (MSHR), female control
      (FSHR), methionine-loaded (+Met) males (MSHR[+Met]) and females (FSHR[+Met]), and
      male SHR with both 17beta-estradiol (E2) and Met administration (MSHR[+E2+Met]).
      Treated groups received Met (1g/kg body weight per day) in water for 6 weeks.
      Systolic blood pressure (SBP) was monitored weekly. Aortic contractile
      (phenylephrine-induced) and relaxant (acetylcholine-induced as endothelium
      dependent relaxation, or EDR) responses as well as endothelial suppression (with
      nitric oxide synthase inhibitor) were evaluated at the end of experiments. Serum
      homocysteine (Hcy) level was also determined. Met overloading caused a nearly 3
      fold increase in serum Hcy in each gender (moderate hyperhomocysteinemia, or
      HHcy). As age increased, SBP increased in all groups; FSHR(+Met) had the least
      elevation and significantly less increase of SBP than FSHR at the end of 6 weeks.
      There was also a significant increase of EDR in FSHR(+Met) compared with both
      FSHR and MSHR(+Met). FSHR(+Met) had the highest level of endothelium suppression.
      Furthermore, EDR in MSHR(+E2+Met) was significantly higher than that in
      MSHR(+Met). Direct Hcy feeding appeared to reduce the development of hypertension
      in female SHR in 3 weeks. Hence, SBP development was partially alleviated,
      whereas EDR and endothelium suppression were enhanced in female SHR with HHcy. E2
      could mimic the gender-dependent effect of HHcy on EDR enhancement in MSHR;
      moreover, reduction of SBP development occurred in Hcy-fed FSHR.

PMID- 12215475
TI  - ACE inhibitor improves insulin resistance in diabetic mouse via bradykinin and
      NO.
AB  - Improvement of insulin resistance by ACE inhibitors has been suggested; however,
      this mechanism has not been proved. We postulated that activation of the
      bradykinin-nitric oxide (NO) system by an ACE inhibitor enhances glucose uptake
      in peripheral tissues by means of an increase in translocation of glucose
      transporter 4 (GLUT4), resulting in improvement of insulin resistance.
      Administration of an ACE inhibitor, temocapril, significantly decreased plasma
      glucose and insulin concentrations in type 2 diabetic mouse KK-Ay. Mice treated
      with temocapril showed a smaller plasma glucose increase after glucose load. We
      demonstrated that temocapril treatment significantly enhanced 2-[3H]-deoxy-D
      glucose (2-DG) uptake in skeletal muscle but not in white adipose tissue.
      Administration of a bradykinin B2 receptor antagonist, Hoe140, or an NO synthase
      inhibitor, L-NAME, attenuated the enhanced glucose uptake by temocapril.
      Moreover, we observed that translocation of GLUT4 to the plasma membrane was
      significantly enhanced by temocapril treatment without influencing insulin
      receptor substrate-1 phosphorylation. In L6 skeletal muscle cells, 2-DG uptake
      was increased by temocaprilat, and Hoe140 inhibited this effect of temocaprilat
      but not that of insulin. These results suggest that temocapril would improve
      insulin resistance and glucose intolerance through increasing glucose uptake,
      especially in skeletal muscle at least in part through enhancement of the
      bradykinin-NO system and consequently GLUT4 translocation.

PMID- 12215476
TI  - Augmented upregulation by c-fos of angiotensin subtype 1 receptor in nucleus
      tractus solitarii of spontaneously hypertensive rats.
AB  - Our laboratory demonstrated previously that spontaneously hypertensive rats (SHR)
      exhibited an elevated basal Fos expression in the nucleus tractus solitarii
      (NTS), the terminal site for primary baroreceptor afferents, and that Fos protein
      is required for the re-expression of angiotensin subtype 1 receptor (AT1R) mRNA
      in the NTS after baroreceptor activation. The present study evaluated the
      hypothesis that this re-expression of AT1R is augmented in SHR and is promoted by
      the heightened Fos expression. Reverse transcription-polymerase chain reaction
      analysis revealed that baroreceptor activation via sustained increase in systemic
      arterial pressure resulted in a discernible reduction in the expression of AT1R
      mRNA at the dorsomedial medulla of SHR and normotensive Wistar-Kyoto rats.
      However, SHR manifested an appreciably larger magnitude of decline, followed by a
      faster time course of re-expression in AT1R mRNA. Parallel findings were obtained
      from the pressor response induced by microinjection unilaterally of angiotensin
      II (40 pmol) into the NTS. Whereas the re-expression of AT1R at both
      transcriptional and functional expression levels after baroreceptor activation
      was discernibly blunted by prior bilateral application into the NTS of an
      antisense c-fos oligonucleotide (50 pmol), the suppression in SHR was again
      significantly more intense. Control pretreatment with the corresponding sense or
      scrambled c-fos oligonucleotide was ineffective. We conclude that the heightened
      Fos expression in SHR is causatively related to the augmented re-expression of
      AT1R in the NTS at both transcriptional and functional levels.

PMID- 12215477
TI  - Catecholamine-related gene expression correlates with blood pressures in SHR.
AB  - In this study we aimed to determine whether the levels of gene expression for
      phenylethanolamine-N-methyltransferase (PNMT), noradrenaline transporter (NAT),
      alpha1A-receptor (alpha1A-R), and alpha2A-receptor (alpha2A-R) vary with resting
      systolic blood pressure in spontaneously hypertensive rats (SHR) compared with
      normotensive Wistar-Kyoto (WKY) or Sprague-Dawley (SD) rats. Sites examined
      included central and peripheral regions associated with the control of arterial
      pressure. Twenty week old SD (n=6), WKY (n=6), and SHR (n=6) were used. Systolic
      blood pressure was measured using tail cuff plethysmography 2 weeks before tissue
      extraction. RNA was isolated and reverse-transcribed into cDNA. Gene expression
      levels were measured, using quantitative real time PCR, relative to the
      expression of GAPDH. PNMT, NAT, and alpha(1A)-R mRNA expression was significantly
      greater in SHR tissue samples compared with normotensives. In the rostral
      ventrolateral medulla, PNMT mRNA in SHR was 3 times greater than that in WKY
      (SHR: 0.82+/-0.02%; WKY: 0.29+/-0.02%). The amount of alpha(2A)-R mRNA was
      significantly lower in SHR compared with normotensives. For example, the level of
      alpha(2A)-R mRNA in spinal cord of SHR was 3 times less than that found in WKY
      (SHR: 1.85+/-0.04%; WKY: 3.26+/-0.07%). PNMT, NAT, and alpha(1A)-R mRNA levels
      were positively correlated with systolic blood pressure in all central tissue
      investigated. Conversely, alpha2A-R mRNA levels in central sites were negatively
      correlated with systolic blood pressure. Clearly, a decrease in central alpha2A-R
      and an increase in alpha1A-R is consistent with the elevated blood pressure and
      sympathetic activity observed in SHR.

PMID- 12215478
TI  - Angiotensin II induces catecholamine release by direct ganglionic excitation.
AB  - Angiotensin II (ANG) is known to facilitate catecholamine release from peripheral
      sympathetic neurons by enhancing depolarization-dependent exocytosis. In
      addition, a direct excitation by ANG of peripheral sympathetic nerve activity has
      recently been described. This study determined the significance of the latter
      mechanism for angiotensin-induced catecholamine release in the pithed rat. Rats
      were anesthetized and instrumented for measuring either hemodynamics and renal
      sympathetic nerve activity or plasma catecholamine concentrations in response to
      successively increasing doses of angiotensin infusions. Even during ganglionic
      blockade by hexamethonium (20 mg/kg), angiotensin dose-dependently elevated
      sympathetic nerve activity, whereas blood pressure-equivalent doses of
      phenylephrine were ineffective. Independently of central nervous sympathetic
      activity and ganglionic transmission, angiotensin (0.1 to 1 microg/kg) also
      induced an up-to 27-fold increase in plasma norepinephrine levels, reaching 2.65
      ng/mL. Preganglionic electrical stimulation (0.5 Hz) raised basal norepinephrine
      levels 11-fold and further enhanced the angiotensin-induced increase in
      norepinephrine (4.04 ng/mL at 1 microg/kg ANG). Stimulation of sympathetic nerve
      activity and norepinephrine release were suppressed by candesartan (1 mg/kg) or
      tetrodotoxin (100 microg/kg), respectively. Angiotensin enhanced plasma
      norepinephrine, heart rate, and sympathetic nerve activity at similar threshold
      doses (0.3 to 1 microg/kg), but raised blood pressure at a significantly lower
      dose (0.01 microg/kg). It is concluded that direct stimulation of ganglionic
      angiotensin type 1 (AT(1)) receptors arouses electrical activity in sympathetic
      neurons, leading to exocytotic junctional catecholamine release. In both the
      absence and presence of preganglionic sympathetic activity, this mechanism
      contributes significantly to ANG-induced enhancement of catecholamine release.

PMID- 12215481
TI  - Endothelin antagonists and hypertension: a question of dose?

PMID- 12215479
TI  - Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity.
AB  - Humans have elevated serum uric acid as a result of a mutation in the urate
      oxidase (uricase) gene that occurred during the Miocene. We hypothesize that the
      mutation provided a survival advantage because of the ability of hyperuricemia to
      maintain blood pressure under low-salt dietary conditions, such as prevailed
      during that period. Mild hyperuricemia in rats acutely increases blood pressure
      by a renin-dependent mechanism that is most manifest under low-salt dietary
      conditions. Chronic hyperuricemia also causes salt sensitivity, in part by
      inducing preglomerular vascular disease. The vascular disease is mediated in part
      by uric acid-induced smooth muscle cell proliferation with activation of mitogen
      activated protein kinases and stimulation of cyclooxygenase-2 and platelet
      derived growth factor. Although it provided a survival advantage to early
      hominoids, hyperuricemia may have a major role in the current cardiovascular
      disease epidemic.

PMID- 12215482
TI  - Nitric oxide and regulation of arterial elasticity: right idea, wrong vascular
      bed?

PMID- 12215483
TI  - Nitrated lipids: defining their bioactivity.

PMID- 12215484
TI  - PPARgamma and vascular inflammation: adding another piece to the puzzle.

PMID- 12215485
TI  - Nitrolinoleate inhibits superoxide generation, degranulation, and integrin
      expression by human neutrophils: novel antiinflammatory properties of nitric
      oxide-derived reactive species in vascular cells.
AB  - Nitration of unsaturated fatty acids such as linoleate by NO-derived reactive
      species forms novel derivatives (including nitrolinoleate [LNO2]) that can
      stimulate smooth muscle relaxation and block platelet activation by either
      NO/cGMP or cAMP-dependent mechanisms. Here, LNO2 was observed to inhibit human
      neutrophil function. LNO2, but not linoleic acid or the nitrated amino acid 3
      nitrotyrosine, dose-dependently (0.2 to 1 micromol/L) inhibited superoxide (O2*-)
      generation, Ca2+ influx, elastase release, and CD11b expression in response to
      either phorbol 12-myristate 13-acetate or N-formyl-Met-Leu-Phe. LNO2 did not
      elevate cGMP, and inhibition of guanylate cyclase by 1H-[1,2,4]oxadiazole[4,3
      a]quinoxalin-1-one did not restore neutrophil responses, ruling out a role for
      NO. In contrast, LNO2 caused elevations in intracellular cAMP in the presence and
      absence of phosphodiesterase inhibition, suggesting activation of adenylate
      cyclase. Compared with phorbol 12-myristate 13-acetate-activated neutrophils, N
      formyl-Met-Leu-Phe-activated neutrophils were more susceptible to the inhibitory
      effects of LNO2, indicating that LNO2 may inhibit signaling both upstream and
      downstream of protein kinase C. These data suggest novel signaling actions for
      LNO2 in mediating its potent inhibitory actions. Thus, nitration of lipids by NO
      derived reactive species yields products with antiinflammatory properties,
      revealing a novel mechanism by which NO-derived nitrated biomolecules can
      influence the progression of vascular disease.

PMID- 12215486
TI  - Regulation of smooth muscle cell differentiation by AT-rich interaction domain
      transcription factors Mrf2alpha and Mrf2beta.
AB  - Despite the importance of vascular smooth muscle cells in the regulation of blood
      vessel function, the molecular mechanisms governing their development and
      differentiation remain poorly understood. Using an in vitro system whereby a
      pluripotent neural crest cell line (MONC-1) can be induced to differentiate into
      smooth muscle cells, we isolated a cDNA fragment that was robustly induced during
      this differentiation process. Sequence analysis revealed high homology to a
      partial cDNA termed modulator recognition factor 2 (Mrf2). Because the full
      length cDNA has not been reported, we cloned the full-length Mrf2 cDNA by cDNA
      library screening and 5' rapid amplification of cDNA ends and identified two
      isoforms of Mrf2 (alpha [3.0 kb] and beta [3.7 kb]) that differ in the N-terminus
      but share the DNA-binding domain. Protein homology analysis suggests that Mrf2 is
      a member of the AT-rich interaction domain family of transcription factors, which
      are known to be critically involved in the regulation of development and cellular
      differentiation. Mrf2alpha and Mrf2beta are highly induced during in vitro
      differentiation of MONC-1 cells into smooth muscle cells, and Mrf2alpha is
      expressed in adult mouse cardiac and vascular tissues. To define the function of
      Mrf2, we overexpressed both isoforms in 3T3 fibroblast cells and observed an
      induction of smooth muscle marker genes, including smooth muscle alpha-actin and
      smooth muscle 22alpha. Furthermore, Mrf2alpha and Mrf2beta retarded cellular
      proliferation. These data implicate Mrf2 as a novel regulator of smooth muscle
      cell differentiation and proliferation.

PMID- 12215487
TI  - Nitric oxide-induced motility in aortic smooth muscle cells: role of protein
      tyrosine phosphatase SHP-2 and GTP-binding protein Rho.
AB  - We have previously reported that SHP-2 upregulation is necessary for NO
      stimulated motility in differentiated rat aortic smooth muscle cells. We now test
      the hypothesis that upregulation of SHP-2 is necessary and sufficient to
      stimulate cell motility. Overexpression of SHP-2 via recombinant adenoviral
      vector stimulated motility to the same extent as NO, whereas the expression of
      C463S-SHP-2, the dominant-negative SHP-2 allele, blocked the motogenic effect of
      NO. On the basis of previous studies, we next tested the hypothesis that NO
      decreases RhoA activity and that this event is necessary and sufficient to
      explain NO-induced motogenesis. We found that NO decreased RhoA activity in a
      concentration-dependent manner. Moreover, a dominant-negative SHP-2 allele, DSH2,
      blocked the NO-induced inhibition of RhoA activity, indicating that upregulation
      of SHP-2 is necessary for this event. Expression of G14V-RhoA, the constitutively
      active RhoA allele, decreased cell motility and blocked the motogenic effect of
      NO, whereas the expression of T19N-RhoA, the dominant-negative RhoA allele,
      increased cell motility to an extent similar to that induced by NO. Dominant
      negative RhoA reversed the effect of dominant-negative SHP-2, indicating that
      RhoA functions downstream from SHP-2. To investigate events downstream from RhoA,
      we treated cells with fasudil, a selective Rho kinase inhibitor, and found that
      it increased cell motility. These results indicate that upregulation of SHP-2,
      leading to downregulation of RhoA, which is followed by decreased Rho kinase
      activity, is a sequence of events necessary and sufficient to explain NO-induced
      cell motility in differentiated aortic smooth muscle cells. The results may be of
      relevance to in vivo events such as neointimal formation, angiogenesis, and
      vasculogenesis.

PMID- 12215488
TI  - Galpha(q) and Gbetagamma regulate PAR-1 signaling of thrombin-induced NF-kappaB
      activation and ICAM-1 transcription in endothelial cells.
AB  - As thrombin binding to the G protein-coupled proteinase activated receptor-1 (PAR
      1) induces endothelial adhesivity to leukocytes through NF-kappaB activation and
      intercellular adhesion molecule-1 (ICAM-1) expression, we determined the
      signaling pathways mediating the response. Studies showed that the heterotrimeric
      G proteins, Galpha(q), and the Gbetagamma dimer were key determinants of the PAR
      1 agonist peptide (TFLLRNPNDK)-induced NF-kappaB activation and ICAM-1 expression
      in endothelial cells. Cotransfection of RGS3T, a regulator of G-protein signaling
      that inhibits Galpha(q), or alpha-transducin (Galpha(t)), a scavenger of the
      Gbetagamma, markedly decreased NF-kappaB activity induced by PAR-1 activation. We
      determined the downstream signaling targets activated by Galpha(q) and Gbetagamma
      that mediate NF-kappaB activation. Expression of the kinase-defective protein
      kinase C (PKC)-delta mutant inhibited NF-kappaB activation induced by the
      constitutively active Galpha(q) mutant, but had no effect on NF-kappaB activity
      induced by Gbeta(1)gamma(2). In related experiments, NF-kappaB as well as ICAM-1
      promoter activation induced by Gbeta(1)gamma(2) were inhibited by the expression
      of the dominant-negative mutant of 85-kDa regulatory subunit of PI 3-kinase;
      however, the expression of this mutant had no effect on the response induced by
      activated Galpha(q). Cotransfection of the catalytically inactive Akt mutant
      inhibited the NF-kappaB activation induced by the constitutively active PI 3
      kinase mutant as well as that by the activated forms of Galpha(q) and PKC-delta.
      These results support a model in which ligation of PAR-1 induces NF-kappaB
      activation and ICAM-1 transcription by the engagement of parallel Galphaq/PKC
      delta and Gbetagamma/PI3-kinase pathways that converge at Akt.

PMID- 12215490
TI  - Luminal Ca2+ controls termination and refractory behavior of Ca2+-induced Ca2+
      release in cardiac myocytes.
AB  - Despite extensive research, the mechanisms responsible for the graded nature and
      early termination of Ca2+-induced Ca2+ release (CICR) from the sarcoplasmic
      reticulum (SR) in cardiac muscle remain poorly understood. Suggested mechanisms
      include cytosolic Ca2+-dependent inactivation/adaptation and luminal Ca2+
      dependent deactivation of the SR Ca2+ release channels/ryanodine receptors
      (RyRs). To explore the importance of cytosolic versus luminal Ca2+ regulatory
      mechanisms in controlling CICR, we assessed the impact of intra-SR Ca2+ buffering
      on global and local Ca2+ release properties of patch-clamped or permeabilized rat
      ventricular myocytes. Exogenous, low-affinity Ca2+ buffers (5 to 20 mmol/L ADA,
      citrate or maleate) were introduced into the SR by exposing the cells to
      "internal" solutions containing the buffers. Enhanced Ca2+ buffering in the SR
      was confirmed by an increase in the total SR Ca2+ content, as revealed by
      application of caffeine. At the whole-cell level, intra-SR [Ca2+] buffering
      dramatically increased the magnitude of Ca2+ transients induced by I(Ca) and
      deranged the smoothly graded I(Ca)-SR Ca2+ release relationship. The amplitude
      and time-to-peak of local Ca2+ release events, Ca2+ sparks, as well as the
      duration of local Ca2+ release fluxes underlying sparks were increased up to 2-
      to 3-fold. The exogenous Ca2+ buffers in the SR also reduced the frequency of
      repetitive activity observed at individual release sites in the presence of the
      RyR activator Imperatoxin A. We conclude that regulation of RyR openings by local
      intra-SR [Ca2+] is responsible for termination of CICR and for the subsequent
      restitution behavior of Ca2+ release sites in cardiac muscle.

PMID- 12215489
TI  - Angiotensin II stimulation of NAD(P)H oxidase activity: upstream mediators.
AB  - Angiotensin II (Ang II)-stimulated hypertrophy of vascular smooth muscle cells is
      mediated by reactive oxygen species (ROS) derived from NAD(P)H oxidases. The
      upstream signaling mechanisms by which Ang II activates these oxidases are
      unclear but may include protein kinase C, tyrosine kinases, phosphatidylinositol
      3-kinase, and Rac, a small molecular weight G protein. We found that Ang II
      stimulated ROS production is biphasic. The first phase occurs rapidly (peak at 30
      seconds) and is dependent on protein kinase C activation. The larger second phase
      of ROS generation (peak at 30 minutes) requires Rac activation, because
      inhibition of Rac by either Clostridium difficile toxin A or dominant-negative
      Rac significantly inhibits Ang II-induced ROS production. Phosphatidylinositol-3
      kinase inhibitors (wortmannin or LY294002) and the epidermal growth factor (EGF)
      receptor kinase blocker AG1478 attenuate both Rac activation and ROS generation.
      The upstream activator of EGF receptor transactivation, c-Src, is also required
      for ROS generation, because PP1, an Src kinase inhibitor, abrogates the Ang II
      stimulation of both responses. These results suggest that c-Src, EGF receptor
      transactivation, phosphatidylinositol-3-kinase, and Rac play important roles in
      the sustained Ang II-mediated activation of vascular smooth muscle cell NAD(P)H
      oxidases and provide insight into the integrated signaling mechanisms whereby Ang
      II stimulation leads to activation of the growth-related NAD(P)H oxidases.

PMID- 12215491
TI  - Identification of gating modes in single native Na+ channels from human atrium
      and ventricle.
AB  - The aim of the present study was to investigate the single-channel properties of
      different gating modes in the native human cardiac Na+ channel. Patch-clamp
      experiments were performed at low noise using ultrathick-walled pipettes. In 17
      cell-attached patches containing only one channel, fast back and forth switching
      between five different Na+-channel gating modes (F-mode, M1-mode, M2-mode, S
      mode, and P-mode) was identified, but no difference in the gating properties was
      found between normal and diseased cardiomyocytes from atrium or ventricle,
      respectively. Hodgkin-Huxley fits to the ensemble-averaged currents yielded the
      activation-time (tau(m)) and inactivation-time (tau(h)) constants. tau(m) was
      comparably fast in the F-mode, M1-mode, M2-mode, and S-mode (0.15 ms) and slow in
      the P-mode (0.3 ms). tau(h) ranged from 0.35 ms (F-mode) to 4.5 ms (S-mode and P
      mode). The mean open-channel lifetime (tau(o)) was shortest in the F-mode and P
      mode (0.15 ms) and longest in the S-mode (1.25 ms). The time before which half of
      the first channel openings occurred (t(0.5)) was comparably short in the F-mode,
      M1-mode, M2-mode, and S-mode (0.3 ms) and long in the P-mode (0.9 ms). It is
      concluded that (1) a single native human cardiac Na+ channel can be recorded at
      low noise, (2) this channel can change its gating properties at a time scale of
      milliseconds, (3) lifetimes of the observed gating modes are short ranging from
      milliseconds to seconds only, and (4) the gating modes are characterized by
      specific activation and inactivation kinetics and differ at least in their mean
      open time and first latency.

PMID- 12215492
TI  - Vascular inflammation is negatively autoregulated by interaction between
      CCAAT/enhancer-binding protein-delta and peroxisome proliferator-activated
      receptor-gamma.
AB  - CCAAT/enhancer-binding proteins (C/EBPs) upregulate transcription of various
      inflammatory cytokines and acute phase proteins, such as interleukin (IL)-1beta,
      IL-6, tumor necrosis factor-alpha, and cyclooxygenase-2. Recent studies have
      demonstrated that peroxisome proliferator-activated receptor (PPAR)-gamma is
      present in atherosclerotic lesions, and negatively regulates expression of these
      genes. Interestingly, PPAR-gamma gene promoter has tandem repeats of C/EBP
      binding motif, and C/EBP-delta plays a pivotal role in transactivation of PPAR
      gamma gene. It has been well known that the interaction between C/EBPs and PPAR
      gamma plays a central role in maintaining adipocyte differentiation and
      glucometabolism; however, the relationship between PPAR-gamma and C/EBPs in the
      vessel wall remains unclear. In the present study, we showed that a high level of
      C/EBP-delta expression induced by inflammation positively regulated transcription
      and protein expression of PPAR-gamma in vascular smooth muscle cells (VSMCs). On
      the other hand, PPAR-gamma ligands troglitazone, pioglitazone, and 15-deoxy
      Delta(12,14)-prostaglandin J(2) inhibited IL-1beta-induced IL-6 expression at a
      transcriptional revel in VSMCs. Functional promoter analysis revealed that PPAR
      gamma ligands inhibited IL-1beta-induced transactivation of IL-6 gene via
      suppression of not only nuclear factor-kappaB but also C/EBP-DNA binding.
      Moreover, PPAR-gamma ligands suppressed protein expression and transcription of
      C/EBP-delta through dephosphorylation of signal transducer and activator of
      transcription 3. These findings strongly suggest that C/EBP-delta is negatively
      autoregulated via transactivation of PPAR-gamma. This feedback mechanism probably
      downregulates transcription of inflammatory cytokines and acute phase proteins,
      and modulates inflammatory responses in the early process of atherosclerosis.

PMID- 12215493
TI  - Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac
      contractility.
AB  - The orphan receptor APJ and its recently identified endogenous ligand, apelin,
      exhibit high levels of mRNA expression in the heart. However, the functional
      importance of apelin in the cardiovascular system is not known. In isolated
      perfused rat hearts, infusion of apelin (0.01 to 10 nmol/L) induced a dose
      dependent positive inotropic effect (EC50: 33.1+/-1.5 pmol/L). Moreover, preload
      induced increase in dP/dt(max) was significantly augmented (P<0.05) in the
      presence of apelin. Inhibition of phospholipase C (PLC) with U-73122 and
      suppression of protein kinase C (PKC) with staurosporine and GF-109203X markedly
      attenuated the apelin-induced inotropic effect (P<0.001). In addition,
      zoniporide, a selective inhibitor of Na+-H+ exchange (NHE) isoform-1, and KB
      R7943, a potent inhibitor of the reverse mode Na+-Ca2+ exchange (NCX),
      significantly suppressed the response to apelin (P<0.001). Perforated patch-clamp
      recordings showed that apelin did not modulate L-type Ca2+ current or voltage
      activated K+ currents in isolated adult rat ventricular myocytes. Apelin mRNA was
      markedly downregulated in cultured neonatal rat ventricular myocytes subjected to
      mechanical stretch and in vivo in two models of chronic ventricular pressure
      overload. The present study provides the first evidence for the physiological
      significance of apelin in the heart. Our results show that apelin is one of the
      most potent endogenous positive inotropic substances yet identified and that the
      inotropic response to apelin may involve activation of PLC, PKC, and sarcolemmal
      NHE and NCX.

PMID- 12215494
TI  - Interleukin-18/interleukin-18 binding protein signaling modulates ischemia
      induced neovascularization in mice hindlimb.
AB  - Identification of factors that may stimulate ischemia-induced neovascularization
      without increasing atherosclerotic plaque progression is of major therapeutic
      importance. We hypothesized that interleukin-18 binding protein (IL-18BP), a
      major antiinflammatory protein with plaque-stabilizing activities, may affect the
      neovascularization in mice ischemic hindlimb. Ischemia was produced by artery
      femoral occlusion in mice that were subjected to in vivo intramuscular
      electrotransfer of either an empty plasmid or a murine IL-18BP plasmid.
      Angiographic score, capillary density (CD31 staining), and laser Doppler
      perfusion data at day 28 showed significant improvement in ischemic/nonischemic
      leg ratio by respectively 1.6-, 1.4-, and 1.5-fold in IL-18BP-treated mice
      compared with controls (P<0.01). This was associated with a significant 2-fold
      increase in both vascular endothelial growth factor (VEGF) and phospho-Akt
      protein content in the ischemic hindlimb of IL-18BP-treated mice (P<0.05).
      Similar results were obtained in IL-18-deficient mice. Because bone marrow
      derived endothelial progenitor cells (BM-EPCs) are involved in postnatal
      vasculogenesis, EPCs were isolated and cultivated from bone marrow mononuclear
      cells. IL-18BP treatment led to a significant 1.8-fold increase in the percentage
      of BM-EPCs characterized as cells positive for both AcLDL-Dil and von Willebrand
      factor (P<0.001). In conclusion, IL-18BP stimulates ischemia-induced
      neovascularization in association with an activation of VEGF/Akt signaling and an
      increase in BM-EPCs mobilization and differentiation. Our findings strongly
      suggest a major antiangiogenic role of endogenous IL-18 in postischemic injury.

PMID- 12215495
TI  - Molecular indetermination in the transition to error catastrophe: systematic
      elimination of lymphocytic choriomeningitis virus through mutagenesis does not
      correlate linearly with large increases in mutant spectrum complexity.
AB  - Studies with several RNA viruses have shown that enhanced mutagenesis resulted in
      decreases of infectivity or virus extinction, as predicted from virus entry into
      error catastrophe. Here we report that lymphocytic choriomeningitis virus, the
      prototype arenavirus, is extremely susceptible to extinction mutagenesis by the
      base analog 5-fluorouracil. Virus elimination was preceded by increases in
      complexity of the mutant spectra of treated populations. However, careful
      molecular comparison of the mutant spectra of several genomic segments suggests
      that the largest increases in mutation frequency do not predict virus extinction.
      Highly mutated viral genomes have escaped detection presumably because
      lymphocytic choriomeningitis virus replicates at or near the error threshold, and
      genomes in the transition toward error catastrophe may have an extremely short
      half-life and escape detection with state-of-the-art cloning and sequencing
      technologies.

PMID- 12215496
TI  - Purification and electron microscopic visualization of functional human
      spliceosomes.
AB  - Pre-mRNA splicing takes place in a large and highly dynamic complex known as the
      spliceosome. Here we report the optimization of a maltose-binding protein (MBP)
      affinity-purification method to isolate functional spliceosomes for electron
      microscopic analysis. Visualization of the spliceosome preparations revealed
      distinct 40-60 nm particles. Immunogold-conjugated antibodies to spliceosome
      components specifically label these particles, which are eliminated by treatment
      with either RNase or protease. Moreover, spliceosomes assembled on two different
      pre-mRNAs are indistinguishable. This first visualization of purified functional
      spliceosomes assembled in vitro reveals striking structural features, including
      one or more central cavities and multiple elongate lobes.

PMID- 12215498
TI  - Plant disease susceptibility genes?

PMID- 12215497
TI  - The binding protein of corticotropin-releasing factor: ligand-binding site and
      subunit structure.
AB  - Corticotropin-releasing factor (CRF), recognized as an important stress factor,
      binds to a CRF receptor and a CRF-binding protein (CRFBP) that represents a
      reservoir of endogenous CRF. Although CRFBP was observed to dimerize, at least in
      part, the ligand was found to be exclusively bound to the monomer-as indicated by
      photoaffinity labeling. We localized the CRF binding site by using photoaffinity
      labeling in combination with different mass spectrometric techniques. The amino
      acid residues Arg-23 and Arg-36 of CRFBP were identified as the sites of
      photoincorporation of monofunctional and bifunctional photoprobes designed on the
      basis of the amino acid sequence of human/rat CRF(6-33). It was, therefore,
      concluded that the sequence of amino acid residues 23-36 of CRFBP is involved in
      ligand binding. Our data are in support of an antiparallel alignment of the
      photoprobe with the amino acid residues 23-36 of the CRFBP monomer.

PMID- 12215499
TI  - Arabidopsis research heats up in Seville.

PMID- 12215500
TI  - Arabidopsis mutants reveal multiple roles for sterols in plant development.

PMID- 12215501
TI  - KOBITO1 encodes a novel plasma membrane protein necessary for normal synthesis of
      cellulose during cell expansion in Arabidopsis.
AB  - The cell wall is the major limiting factor for plant growth. Wall extension is
      thought to result from the loosening of its structure. However, it is not known
      how this is coordinated with wall synthesis. We have identified two novel allelic
      cellulose-deficient dwarf mutants, kobito1-1 and kobito1-2 (kob1-1 and kob1-2).
      The cellulose deficiency was confirmed by the direct observation of microfibrils
      in most recent wall layers of elongating root cells. In contrast to the wild
      type, which showed transversely oriented parallel microfibrils, kob1 microfibrils
      were randomized and occluded by a layer of pectic material. No such changes were
      observed in another dwarf mutant, pom1, suggesting that the cellulose defect in
      kob1 is not an indirect result of the reduced cell elongation. Interestingly, in
      the meristematic zone of kob1 roots, microfibrils appeared unaltered compared
      with the wild type, suggesting a role for KOB1 preferentially in rapidly
      elongating cells. KOB1 was cloned and encodes a novel, highly conserved, plant
      specific protein that is plasma membrane bound, as shown with a green fluorescent
      protein-KOB1 fusion protein. KOB1 mRNA was present in all organs investigated,
      and its overexpression did not cause visible phenotypic changes. KOB1 may be part
      of the cellulose synthesis machinery in elongating cells, or it may play a role
      in the coordination between cell elongation and cellulose synthesis.

PMID- 12215502
TI  - Molecular structure of the GARP family of plant Myb-related DNA binding motifs of
      the Arabidopsis response regulators.
AB  - The B motif is a signature of type-B response regulators (ARRs) involved in His
      to-Asp phosphorelay signal transduction systems in Arabidopsis. Homologous motifs
      occur widely in the GARP family of plant transcription factors. To gain general
      insight into the structure and function of B motifs (or GARP motifs), we
      characterized the B motif derived from a representative ARR, ARR10, which led to
      a number of intriguing findings. First, the B motif of ARR10 (named ARR10-B and
      extending from Thr-179 to Ser-242) possesses a nuclear localization signal, as
      indicated by the intracellular localization of a green fluorescent protein-ARR10
      B fusion protein in onion epidermal cells. Second, the purified ARR10-B molecule
      binds specifically in vitro to DNA with the core sequence AGATT. This was
      demonstrated by several in vitro approaches, including PCR-assisted DNA binding
      site selection, gel retardation assays, and surface plasmon resonance analysis.
      Finally, the three-dimensional structure of ARR10-B in solution was determined by
      NMR spectroscopy, showing that it contains a helix-turn-helix structure.
      Furthermore, the mode of interaction between ARR10-B and the target DNA was
      assessed extensively by NMR spectroscopy. Together, these results lead us to
      propose that the mechanism of DNA recognition by ARR10-B is essentially the same
      as that of homeodomains. We conclude that the B motif is a multifunctional domain
      responsible for both nuclear localization and DNA binding and suggest that these
      insights could be applicable generally to the large GARP family of plant
      transcription factors.

PMID- 12215503
TI  - Silencing of phosphoethanolamine N-methyltransferase results in temperature
      sensitive male sterility and salt hypersensitivity in Arabidopsis.
AB  - S-Adenosyl-L-methionine:phosphoethanolamine N-methyltransferase (PEAMT; EC
      2.1.1.103) catalyzes the key step in choline (Cho) biosynthesis, the N
      methylation of phosphoethanolamine. Cho is a vital precursor of the membrane
      phospholipid phosphatidylcholine, which accounts for 40 to 60% of lipids in
      nonplastid plant membranes. Certain plants use Cho to produce the osmoprotectant
      glycine betaine, which confers resistance to salinity, drought, and other
      stresses. An Arabidopsis mutant, t365, in which the PEAMT gene is silenced, was
      identified using a new sense/antisense RNA expression system. t365 mutant plants
      displayed multiple morphological phenotypes, including pale-green leaves, early
      senescence, and temperature-sensitive male sterility. Moreover, t365 mutant
      plants produced much less Cho and were hypersensitive to salinity. These results
      demonstrate that Cho biosynthesis not only plays an important role in plant
      growth and development but also contributes to tolerance to environmental
      stresses. The temperature-sensitive male sterility caused by PEAMT silencing may
      have a potential application in agriculture for engineering temperature-sensitive
      male sterility in important crop plants.

PMID- 12215504
TI  - The identification of CVP1 reveals a role for sterols in vascular patterning.
AB  - Vascular cell axialization refers to the uniform alignment of vascular strands.
      In the Arabidopsis cotyledon vascular pattern1 (cvp1) mutant, vascular cells are
      not arranged in parallel files and are misshapen, suggesting that CVP1 has a role
      in promoting vascular cell polarity and alignment. Characterization of an allelic
      series of cvp1 mutations revealed additional functions of CVP1 in organ expansion
      and elongation. We identified CVP1 and found that it encodes STEROL
      METHYLTRANSFERASE2 (SMT2), an enzyme in the sterol biosynthetic pathway. SMT2 and
      the functionally redundant SMT3 act at a branch point in the pathway that
      mediates sterol and brassinosteroid levels. The SMT2 gene is expressed in a
      number of developing organs and is regulated by various hormones. As predicted
      from SMT2 enzymatic activity, the precursors to brassinosteroid are increased at
      the expense of sterols in cvp1 mutants, identifying a role for sterols in
      vascular cell polarization and axialization.

PMID- 12215505
TI  - Double jeopardy: both overexpression and suppression of a redox-activated plant
      mitogen-activated protein kinase render tobacco plants ozone sensitive.
AB  - In plants, the role of mitogen-activated protein kinase (MAPK) in reactive oxygen
      species (ROS)-based signal transduction processes is elusive. Despite the fact
      that ROS can induce MAPK activation, no direct genetic evidence has linked ROS
      induced MAPK activation with the hypersensitive response, a form of programmed
      cell death. In tobacco, the major ROS-induced MAPK is salicylate-induced protein
      kinase (SIPK). We found through gain-of-function and loss-of-function approaches
      that both overexpression and RNA interference-based suppression of SIPK render
      the plant sensitive to ROS stress. Transgenic lines overexpressing a
      nonphosphorylatable version of SIPK were not ROS sensitive. Analysis of the MAPK
      activation profiles in ROS-stressed transgenic and wild-type plants revealed a
      striking interplay between SIPK and another MAPK (wound-induced protein kinase
      [WIPK]) in the different kinotypes. During continuous ozone exposure, abnormally
      prolonged activation of SIPK was seen in the SIPK-overexpression genotype,
      without WIPK activation, whereas strong and stable activation of WIPK was
      observed in the SIPK-suppressed lines. Thus, one role of activated SIPK in
      tobacco cells upon ROS stimulation appears to be control of the inactivation of
      WIPK.

PMID- 12215506
TI  - Plasmodesma-mediated selective protein traffic between "symplasmically isolated"
      cells probed by a viral movement protein.
AB  - Intercellular communication is essential for differentiation and development. In
      plants, plasmodesmata (PD) form cytoplasmic channels for direct communication.
      During plant development, programmed reduction in PD number and transport
      capacity creates the so-called symplasmic domains. Small fluorescent dyes and
      ions can diffuse among cells within a domain but not across domain boundaries.
      Such symplasmic isolation is thought to allow groups of cells to differentiate
      and develop into tissues with distinct structures and functions. Whether or how
      "symplasmically isolated" cells communicate with one another is poorly
      understood. One well-documented symplasmic domain is the sieve element-companion
      cell (SE-CC) complex in the phloem tissue. We report here that, when produced in
      the CC of transgenic tobacco, the 3a movement protein (3a MP) of Cucumber mosaic
      virus fused to green fluorescent protein (GFP) can traffic out of the SE-CC
      complex via PD. The extent of 3a MP:GFP traffic across the boundary between
      vascular and nonvascular tissues depends on organ type and developmental stage.
      Our findings provide experimental evidence that endogenous machinery exists for
      protein traffic between the symplasmically isolated SE-CC complex and neighboring
      cells. We suggest that PD-mediated traffic of selected macromolecules can be a
      mechanism for symplasmically isolated cells to communicate with one another.

PMID- 12215507
TI  - Disruption of a DNA topoisomerase I gene affects morphogenesis in Arabidopsis.
AB  - The genesis of phyllotaxis, which often is associated with the Fibonacci series
      of numbers, is an old unsolved puzzle in plant morphogenesis. Here, we show that
      disruption of an Arabidopsis topoisomerase (topo) I gene named TOP1alpha affects
      phyllotaxis and plant architecture. The divergence angles and internode lengths
      between two successive flowers were more random in the top1alpha mutant than in
      the wild type. The top1alpha plants sporadically produced multiple flowers from
      one node, and the number of floral organ primordia often was different. The
      mutation also caused the twisting of inflorescences and individual flowers and
      the serration of leaf margins. These morphological abnormalities indicate that
      TOP1alpha may play a critical role in the maintenance of a regular pattern of
      organ initiation. The top1alpha mutant transformed with the RNA interference
      construct for TOP1beta, another topo I gene arrayed tandemly with TOP1alpha, was
      found to be lethal at young seedling stages, suggesting that topo I activity is
      essential in plants.

PMID- 12215508
TI  - PMR6, a pectate lyase-like gene required for powdery mildew susceptibility in
      Arabidopsis.
AB  - The plant genes required for the growth and reproduction of plant pathogens are
      largely unknown. In an effort to identify these genes, we isolated Arabidopsis
      mutants that do not support the normal growth of the powdery mildew pathogen
      Erysiphe cichoracearum. Here, we report on the cloning and characterization of
      one of these genes, PMR6. PMR6 encodes a pectate lyase-like protein with a novel
      C-terminal domain. Consistent with its predicted gene function, mutations in PMR6
      alter the composition of the plant cell wall, as shown by Fourier transform
      infrared spectroscopy. pmr6-mediated resistance requires neither salicylic acid
      nor the ability to perceive jasmonic acid or ethylene, indicating that the
      resistance mechanism does not require the activation of well-described defense
      pathways. Thus, pmr6 resistance represents a novel form of disease resistance
      based on the loss of a gene required during a compatible interaction rather than
      the activation of known host defense pathways.

PMID- 12215509
TI  - Two novel fungal virulence genes specifically expressed in appressoria of the
      rice blast fungus.
AB  - The PMK1 mitogen-activated protein kinase gene regulates appressorium formation
      and infectious hyphae growth in the rice blast fungus. To further characterize
      this mitogen-activated protein kinase pathway, we constructed a subtraction
      library enriched for genes regulated by PMK1. Two genes identified in this
      library, GAS1 and GAS2, encode small proteins that are homologous with gEgh16 of
      the powdery mildew fungus. Both were expressed specifically during appressorium
      formation in the wild-type strains, but neither was expressed in the pmk1 mutant.
      Mutants deleted in GAS1 and GAS2 had no defect in vegetative growth, conidiation,
      or appressoria formation, but they were reduced in appressorial penetration and
      lesion development. Interestingly, deletion of both GAS1 and GAS2 did not have an
      additive effect on appressorial penetration and lesion formation. The GAS1-green
      fluorescent protein and GAS2-green fluorescent protein fusion proteins were
      expressed only in appressoria and localized in the cytoplasm. These two genes may
      belong to a class of proteins specific for filamentous fungi and function as
      novel virulence factors in fungal pathogens.

PMID- 12215510
TI  - ANTHOCYANIN1 of petunia controls pigment synthesis, vacuolar pH, and seed coat
      development by genetically distinct mechanisms.
AB  - ANTHOCYANIN1 (AN1) of petunia is a transcription factor of the basic helix-loop
      helix (bHLH) family that is required for the synthesis of anthocyanin pigments.
      Here, we show that AN1 controls additional aspects of cell differentiation: the
      acidification of vacuoles in petal cells, and the size and morphology of cells in
      the seed coat epidermis. We identified an1 alleles, formerly known as ph6, that
      sustain anthocyanin synthesis but not vacuolar acidification and seed coat
      morphogenesis. These alleles express truncated proteins lacking the C-terminal
      half of AN1, including the bHLH domain, at an approximately 30-fold higher level
      than wild-type AN1. An allelic series in which one, two, or three amino acids
      were inserted into the bHLH domain indicated that this domain is required for
      both anthocyanin synthesis and vacuolar acidification. These findings show that
      AN1 controls more aspects of epidermal cell differentiation than previously
      thought through partially separable domains.

PMID- 12215511
TI  - Role of the Arabidopsis RING-H2 protein RBX1 in RUB modification and SCF
      function.
AB  - The ubiquitin-related protein RUB/Nedd8 is conjugated to members of the cullin
      family of proteins in plants, animals, and fungi. In Arabidopsis, the RUB
      conjugation pathway consists of a heterodimeric E1 (AXR1-ECR1) and a RUB-E2
      called RCE1. The cullin CUL1 is a subunit in SCF-type ubiquitin protein ligases
      (E3s), including the SCF(TIR1) complex, which is required for response to the
      plant hormone auxin. Our previous studies showed that conjugation of RUB to CUL1
      is required for normal SCF(TIR1) function. The RING-H2 finger protein RBX1 is a
      subunit of SCF complexes in fungi and animals. The function of RBX1 is to bind
      the ubiquitin-conjugating enzyme E2 and bring it into close proximity with the E3
      substrate. We have identified two Arabidopsis genes encoding RING-H2 proteins
      related to human RBX1. Studies of one of these proteins indicate that, as in
      animals and fungi, Arabidopsis RBX1 is an SCF subunit. Reduced RBX1 levels result
      in severe defects in growth and development. Overexpression of RBX1 increases RUB
      modification of CUL1. This effect is associated with reduced auxin response and
      severe growth defects similar to those observed in axr1 mutants. As in the axr1
      mutants, RBX1 overexpression stabilizes the SCF(TIR1) substrate AXR2/IAA7. The
      RBX1 protein is a component of SCF complexes in Arabidopsis. In addition to its
      direct role in SCF E3 ligase activity, RBX1 promotes the RUB modification of CUL1
      and probably functions as an E3 ligase in the RUB pathway. Hypermodification of
      CUL1 disrupts SCF(TIR1) function, suggesting that cycles of RUB conjugation and
      removal are important for SCF activity.

PMID- 12215512
TI  - Alteration of oriented deposition of cellulose microfibrils by mutation of a
      katanin-like microtubule-severing protein.
AB  - It has long been hypothesized that cortical microtubules (MTs) control the
      orientation of cellulose microfibril deposition, but no mutants with alterations
      of MT orientation have been shown to affect this process. We have shown
      previously that in Arabidopsis, the fra2 mutation causes aberrant cortical MT
      orientation and reduced cell elongation, and the gene responsible for the fra2
      mutation encodes a katanin-like protein. In this study, using field emission
      scanning electron microscopy, we found that the fra2 mutation altered the normal
      orientation of cellulose microfibrils in walls of expanding cells. Although
      cellulose microfibrils in walls of wild-type cells were oriented transversely
      along the elongation axis, cellulose microfibrils in walls of fra2 cells often
      formed bands and ran in different directions. The fra2 mutation also caused
      aberrant deposition of cellulose microfibrils in secondary walls of fiber cells.
      The aberrant orientation of cellulose microfibrils was shown to be correlated
      with disorganized cortical MTs in several cell types examined. In addition, the
      thickness of both primary and secondary cell walls was reduced significantly in
      the fra2 mutant. These results indicate that the katanin-like protein is
      essential for oriented cellulose microfibril deposition and normal cell wall
      biosynthesis. We further demonstrated that the Arabidopsis katanin-like protein
      possessed MT-severing activity in vitro; thus, it is an ortholog of animal
      katanin. We propose that the aberrant MT orientation caused by the mutation of
      katanin results in the distorted deposition of cellulose microfibrils, which in
      turn leads to a defect in cell elongation. These findings strongly support the
      hypothesis that cortical MTs regulate the oriented deposition of cellulose
      microfibrils that determines the direction of cell elongation.

PMID- 12215513
TI  - Arabidopsis A BOUT DE SOUFFLE, which is homologous with mammalian carnitine acyl
      carrier, is required for postembryonic growth in the light.
AB  - The degradation of storage compounds just after germination is essential to plant
      development, providing energy and molecules necessary for the building of a
      photosynthetic apparatus and allowing autotrophic growth. We identified a bout de
      souffle (bou), a new Arabidopsis mutation. Mutant plants stopped developing after
      germination and degraded storage lipids, but they did not proceed to autotrophic
      growth. Neither leaves nor roots developed in the mutant. However, externally
      added sugar or germination in the dark could bypass this developmental block and
      allowed mutant plants to develop. The mutated gene was cloned using the
      transposon Dissociation as a molecular tag. The gene coding sequence showed
      similarity to those of the mitochondrial carnitine acyl carriers (CACs) or CAC
      like proteins. In animals and yeast, these transmembrane proteins are involved in
      the transport of lipid-derived molecules across mitochondrial membranes for
      energy and carbon supply. The data presented here suggest that BOU identifies a
      novel mitochondrial pathway that is necessary to seedling development in the
      light. The BOU pathway would be an alternative to the well-known glyoxylate
      pathway.

PMID- 12215514
TI  - The regulation of actin organization by actin-depolymerizing factor in elongating
      pollen tubes.
AB  - Pollen tube elongation is a polarized cell growth process that transports the
      male gametes from the stigma to the ovary for fertilization inside the ovules.
      Actomyosin-driven intracellular trafficking and active actin remodeling in the
      apical and subapical regions of pollen tubes are both important aspects of this
      rapid tip growth process. Actin-depolymerizing factor (ADF) and cofilin are actin
      binding proteins that enhance the depolymerization of microfilaments at their
      minus, or slow-growing, ends. A pollen-specific ADF from tobacco, NtADF1, was
      used to dissect the role of ADF in pollen tube growth. Overexpression of NtADF1
      resulted in the reduction of fine, axially oriented actin cables in transformed
      pollen tubes and in the inhibition of pollen tube growth in a dose-dependent
      manner. Thus, the proper regulation of actin turnover by NtADF1 is critical for
      pollen tube growth. When expressed at a moderate level in pollen tubes elongating
      in in vitro cultures, green fluorescent protein (GFP)-tagged NtADF1 (GFP-NtADF1)
      associated predominantly with a subapical actin mesh composed of short actin
      filaments and with long actin cables in the shank. Similar labeling patterns were
      observed for GFP-NtADF1-expressing pollen tubes elongating within the pistil. A
      Ser-6-to-Asp conversion abolished the interaction between NtADF1 and F-actin in
      elongating pollen tubes and reduced its inhibitory effect on pollen tube growth
      significantly, suggesting that phosphorylation at Ser-6 may be a prominent
      regulatory mechanism for this pollen ADF. As with some ADF/cofilin, the in vitro
      actin-depolymerizing activity of recombinant NtADF1 was enhanced by slightly
      alkaline conditions. Because a pH gradient is known to exist in the apical region
      of elongating pollen tubes, it seems plausible that the in vivo actin
      depolymerizing activity of NtADF1, and thus its contribution to actin dynamics,
      may be regulated spatially by differential H(+) concentrations in the apical
      region of elongating pollen tubes.

PMID- 12215515
TI  - Starch synthesis in potato tubers is regulated by post-translational redox
      modification of ADP-glucose pyrophosphorylase: a novel regulatory mechanism
      linking starch synthesis to the sucrose supply.
AB  - Transcriptional and allosteric regulation of ADP-Glc pyrophosphorylase (AGPase)
      plays a major role in the regulation of starch synthesis. Analysis of the
      response after detachment of growing potato tubers from the mother plant revealed
      that this concept requires extension. Starch synthesis was inhibited within 24 h
      of tuber detachment, even though the catalytic subunit of AGPase (AGPB) and
      overall AGPase activity remained high, the substrates ATP and Glc-1-P increased,
      and the glycerate-3-phosphate/inorganic orthophosphate (the allosteric activator
      and inhibitor, respectively) ratio increased. This inhibition was abolished in
      transformants in which a bacterial AGPase replaced the potato AGPase.
      Measurements of the subcellular levels of each metabolite between Suc and starch
      established AGPase as the only step whose substrates increase and mass action
      ratio decreases after detachment of wild-type tubers. Separation of extracts on
      nonreducing SDS gels revealed that AGPB is present as a mixture of monomers and
      dimers in growing tubers and becomes dimerized completely in detached tubers.
      Dimerization led to inactivation of the enzyme as a result of a marked decrease
      of the substrate affinity and sensitivity to allosteric effectors. Dimerization
      could be reversed and AGPase reactivated in vitro by incubating extracts with
      DTT. Incubation of tuber slices with DTT or high Suc levels reduced dimerization,
      increased AGPase activation, and stimulated starch synthesis in vivo. In intact
      tubers, the Suc content correlated strongly with AGPase activation across a range
      of treatments, including tuber detachment, aging of the mother plant,
      heterologous overexpression of Suc phosphorylase, and antisense inhibition of
      endogenous AGPase activity. Furthermore, activation of AGPase resulted in a
      stimulation of starch synthesis and decreased levels of glycolytic intermediates.

PMID- 12215517
TI  - Oscillatory chloride efflux at the pollen tube apex has a role in growth and cell
      volume regulation and is targeted by inositol 3,4,5,6-tetrakisphosphate.
AB  - Oscillatory growth of pollen tubes has been correlated with oscillatory influxes
      of the cations Ca(2+), H(+), and K(+). Using an ion-specific vibrating probe, a
      new circuit was identified that involves oscillatory efflux of the anion Cl(-) at
      the apex and steady influx along the tube starting at 12 microm distal to the
      tip. This spatial coupling of influx and efflux sites predicts that a vectorial
      flux of Cl(-) ion traverses the apical region. The Cl(-) channel blockers 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and 5-nitro-2-(3
      phenylpropylamino)benzoic acid completely inhibited tobacco pollen tube growth at
      80 and 20 microM, respectively. Cl(-) channel blockers also induced increases in
      apical cell volume. The apical 50 micro m of untreated pollen tubes had a mean
      cell volume of 3905 +/- 75 microm(3). DIDS at 80 microM caused a rapid and lethal
      cell volume increase to 6206 +/- 171 microm(3), which is at the point of cell
      bursting at the apex. DIDS was further demonstrated to disrupt Cl(-) efflux from
      the apex, indicating that Cl(-) flux correlates with pollen tube growth and cell
      volume status. The signal encoded by inositol 3,4,5,6-tetrakisphosphate
      [Ins(3,4,5,6)P(4)] antagonized pollen tube growth, induced cell volume increases,
      and disrupted Cl(-) efflux. Ins(3,4,5,6)P(4) decreased the mean growth rate by
      85%, increased the cell volume to 5997 +/- 148 microm(3), and disrupted normal
      Cl(-) efflux oscillations. These effects were specific for Ins(3,4,5,6)P(4) and
      were not mimicked by either Ins(1,3,4,5)P(4) or Ins(1,3,4,5,6)P(5). Growth
      correlation analysis demonstrated that cycles of Cl(-) efflux were coupled to and
      temporally in phase with cycles of growth. A role for Cl(-) flux in the dynamic
      cellular events during growth is assessed. Differential interference contrast
      microscopy and kymographic analysis of individual growth cycles revealed that
      vesicles can advance transiently to within 2 to 4 microm of the apex during the
      phase of maximally increasing Cl(-) efflux, which temporally overlaps the phase
      of cell elongation during the growth cycle. In summary, these investigations
      indicate that Cl(-) ion dynamics are an important component in the network of
      events that regulate pollen tube homeostasis and growth.

PMID- 12215516
TI  - Mitochondrial GFA2 is required for synergid cell death in Arabidopsis.
AB  - Little is known about the molecular processes that govern female gametophyte (FG)
      development and function, and few FG-expressed genes have been identified. We
      report the identification and phenotypic analysis of 31 new FG mutants in
      Arabidopsis. These mutants have defects throughout development, indicating that
      FG-expressed genes govern essentially every step of FG development. To identify
      genes involved in cell death during FG development, we analyzed this mutant
      collection for lines with cell death defects. From this analysis, we identified
      one mutant, gfa2, with a defect in synergid cell death. Additionally, the gfa2
      mutant has a defect in fusion of the polar nuclei. We isolated the GFA2 gene and
      show that it encodes a J-domain-containing protein. Of the J-domain-containing
      proteins in Saccharomyces cerevisiae (budding yeast), GFA2 is most similar to
      Mdj1p, which functions as a chaperone in the mitochondrial matrix. GFA2 is
      targeted to mitochondria in Arabidopsis and partially complements a yeast mdj1
      mutant, suggesting that GFA2 is the Arabidopsis ortholog of yeast Mdj1p. These
      data suggest a role for mitochondria in cell death in plants.

PMID- 12215518
TI  - Suppression of transgene silencing by matrix attachment regions in maize: a dual
      role for the maize 5' ADH1 matrix attachment region.
AB  - Matrix attachment regions (MARs) are DNA sequences that bind an internal nuclear
      network of nonhistone proteins called the nuclear matrix. Thus, they may define
      discrete gene-containing chromatin loops in vivo. We have studied the effects of
      flanking transgenes with MARs on transgene expression levels in maize callus and
      in transformed maize plants. Three MAR elements, two from maize (Adh1 5' MAR and
      Mha1 5' MAR) and one from yeast (ARS1), had very different effects on transgene
      expression that bore no relation to their affinity for the nuclear matrix in
      vitro. In callus, two of the MAR elements (Adh1 5' MAR and ARS1) reduced
      transgene silencing but had no effect on the variability of expression. In
      transgenic plants, Adh1 5' MAR had the effect of localizing beta-glucuronidase
      expression to lateral root initiation sites. A possible model accounting for the
      function of Adh1 5' MAR is discussed.

PMID- 12215519
TI  - The Arabidopsis TUBULIN-FOLDING COFACTOR A gene is involved in the control of the
      alpha/beta-tubulin monomer balance.
AB  - The control of the stoichiometric balance of alpha- and beta-tubulin is important
      during microtubule biogenesis. This process involves several tubulin-folding
      cofactors (TFCs), of which only TFC A is not essential in mammalian in vitro
      systems or in vivo in yeast. Here, we show that the TFC A gene is important in
      vivo in plants. The Arabidopsis gene KIESEL (KIS) shows sequence similarity to
      the TFC A gene. Expression of the mouse TFC A gene under the control of the 35S
      promoter rescues the kis mutation, indicating that KIS is the Arabidopsis
      ortholog of TFC A. kis plants exhibit a range of defects similar to the
      phenotypes associated with impaired microtubule function: plants are reduced in
      size and show meiotic defects, cell division is impaired, and trichomes are
      bulged and less branched. Microtubule density was indistinguishable from that of
      the wild type, but microtubule organization was affected in trichomes and
      hypocotyl cells of dark-grown kis plants. The kis phenotype was rescued by
      overexpression of an alpha-tubulin, indicating that KIS is involved in the
      control of the correct balance of alpha- and beta-tubulin monomers.

PMID- 12215520
TI  - A cysteine-rich extracellular protein, LAT52, interacts with the extracellular
      domain of the pollen receptor kinase LePRK2.
AB  - Pollen germination and pollen tube growth are thought to require extracellular
      cues, but how these cues are perceived and transduced remains largely unknown.
      Pollen receptor kinases are plausible candidates for this role; they might bind
      extracellular ligands and thereby mediate cytoplasmic events required for pollen
      germination and pollen tube growth. To search for pollen-expressed ligands for
      pollen receptor kinases, we used the extracellular domains of three pollen
      specific receptor kinases of tomato (LePRK1, LePRK2, and LePRK3) as baits in a
      yeast two-hybrid screen. We identified numerous secreted or plasma membrane-bound
      candidate ligands. One of these, the Cys-rich protein LAT52, was known to be
      essential during pollen hydration and pollen tube growth. We used in vivo
      coimmunoprecipitation to demonstrate that LAT52 was capable of forming a complex
      with LePRK2 in pollen and to show that the extracellular domain of LePRK2 was
      sufficient for the interaction. Soluble LAT52 can exist in differently sized
      forms, but only the larger form can interact with LePRK2. We propose that LAT52
      might be a ligand for LePRK2.

PMID- 12215521
TI  - Molecular dissection of the gibberellin/abscisic acid signaling pathways by
      transiently expressed RNA interference in barley aleurone cells.
AB  - The interaction between two phytohormones, gibberellins (GA) and abscisic acid
      (ABA), is an important factor regulating the developmental transition from seed
      dormancy to germination. In cereal aleurone tissue, GA induces and ABA suppresses
      the expression of alpha-amylases that are essential for the utilization of starch
      stored in the endosperm. In this work, the signaling pathways mediated by these
      hormones were investigated in the aleurone cells of barley seeds using double
      stranded RNA interference (RNAi) technology. In this tissue, double-stranded RNA
      molecules generated from the transient expression of DNA templates caused a
      sequence-specific suppression of the target genes. We demonstrate that the
      transcription factor, GAMyb, is not only sufficient but also necessary for the GA
      induction of alpha-amylase. Another regulatory protein, SLN1, is shown to be a
      repressor of GA action, and the use of RNAi technology to inhibit the synthesis
      of SLN1 led to derepression of alpha-amylase even in the absence of GA. However,
      this effect still was suppressed by ABA. Although the ABA-induced Ser/Thr protein
      kinase, PKABA1, is known to suppress GA-induced alpha-amylase expression, PKABA1
      RNAi did not hamper the inhibitory effect of ABA on the expression of alpha
      amylase, indicating that a PKABA1-independent signaling pathway also may exist.
      We suggest that the generation of specific RNAi in a transient expression
      approach is a useful technique for elucidating the role of regulatory molecules
      in biological systems in which conventional mutational studies cannot be
      performed easily.

PMID- 12215522
TI  - Loss of Albino3 leads to the specific depletion of the light-harvesting system.
AB  - The chloroplast Albino3 (Alb3) protein is a chloroplast homolog of the
      mitochondrial Oxa1p and YidC proteins of Escherichia coli, which are essential
      components for integrating membrane proteins. In vitro studies in vascular plants
      have revealed that Alb3 is required for the integration of the light-harvesting
      complex protein into the thylakoid membrane. Here, we show that the gene affected
      in the ac29 mutant of Chlamydomonas reinhardtii is Alb3.1. The availability of
      the ac29 mutant has allowed us to examine the function of Alb3.1 in vivo. The
      loss of Alb3.1 has two major effects. First, the amount of light-harvesting
      complex from photosystem II (LHCII) and photosystem I (LHCI) is reduced >10-fold,
      and total chlorophyll represents only 30% of wild-type levels. Second, the amount
      of photosystem II is diminished 2-fold in light-grown cells and nearly 10-fold in
      dark-grown cells. The accumulation of photosystem I, the cytochrome b(6)f
      complex, and ATP synthase is not affected in the ac29 mutant. Mild solubilization
      of thylakoid membranes reveals that Alb3 forms two distinct complexes, a lower
      molecular mass complex of a size similar to LHC and a high molecular mass
      complex. A homolog of Alb3.1, Alb3.2, is present in Chlamydomonas, with 37%
      sequence identity and 57% sequence similarity. Based on the phenotype of ac29,
      these two genes appear to have mostly nonredundant functions.

PMID- 12215523
TI  - Purified box C/D snoRNPs are able to reproduce site-specific 2'-O-methylation of
      target RNA in vitro.
AB  - Small nucleolar RNAs (snoRNAs) are associated in ribonucleoprotein particles
      localized to the nucleolus (snoRNPs). Most of the members of the box C/D family
      function in directing site-specific 2'-O-methylation of substrate RNAs. Although
      the selection of the target nucleotide requires the antisense element and the
      conserved box D or D' of the snoRNA, the methyltransferase activity is supposed
      to reside in one of the protein components. Through protein tagging of a snoRNP
      specific factor, we purified to homogeneity box C/D snoRNPs from the yeast
      Saccharomyces cerevisiae. Mass spectrometric analysis demonstrated the presence
      of Nop1p, Nop58p, Nop56p, and Snu13p as integral components of the particle. We
      show that purified snoRNPs are able to reproduce the site-specific methylation
      pattern on target RNA and that the predicted S-adenosyl-L-methionine-binding
      region of Nop1p is responsible for the catalytic activity.

PMID- 12215524
TI  - Isolation and characterization of new proliferating cell nuclear antigen (POL30)
      mutator mutants that are defective in DNA mismatch repair.
AB  - A number of studies have suggested a role for proliferating cell nuclear antigen
      (PCNA) in DNA mismatch repair (MMR). However, the majority of mutations in the
      POL30 gene encoding PCNA that cause MMR defects also cause replication and other
      repair defects that contribute to the increased mutation rate caused by these
      mutations. Here, 20 new pol30 mutants were identified and screened for MMR and
      other defects, resulting in the identification of two mutations, pol30-201 and
      pol30-204, that appear to cause MMR defects but little if any other defects. The
      pol30-204 mutation altered an amino acid (C81R) in the monomer-monomer interface
      region and resulted in a partial general MMR defect and a defect in MSH2-MSH6
      binding in vitro. The pol30-201 mutation altered an amino acid (C22Y) located on
      the surface of the PCNA trimer that slides over the DNA but did not cause a
      defect in MSH2-MSH6 binding in vitro. The pol30-201 mutation caused an
      intermediate mutator phenotype. However, the pol30-201 mutation caused almost a
      complete defect in the repair of AC and GT mispairs and only a small defect in
      the repair of a "+T" insertion, an effect similar to that caused by an msh6Delta
      mutation, indicating that pol30-201 primarily effects MSH6-dependent MMR. The
      chromosomal double mutant msh3-FF>AA msh6-FF>AA eliminating the conserved FF
      residues of the PCNA interacting motif of these proteins caused a small (<10%)
      defect in MMR but showed synergistic interactions with mutations in POL30,
      indicating that the FF>AA substitution may not eliminate PCNA interactions in
      vivo. These results indicate that the interaction between PCNA and MMR proteins
      is more complex than was previously appreciated.

PMID- 12215525
TI  - The GCN2 eIF2alpha kinase is required for adaptation to amino acid deprivation in
      mice.
AB  - The GCN2 eIF2alpha kinase is essential for activation of the general amino acid
      control pathway in yeast when one or more amino acids become limiting for growth.
      GCN2's function in mammals is unknown, but must differ, since mammals, unlike
      yeast, can synthesize only half of the standard 20 amino acids. To investigate
      the function of mammalian GCN2, we have generated a Gcn2(-/-) knockout strain of
      mice. Gcn2(-/-) mice are viable, fertile, and exhibit no phenotypic abnormalities
      under standard growth conditions. However, prenatal and neonatal mortalities are
      significantly increased in Gcn2(-/-) mice whose mothers were reared on leucine-,
      tryptophan-, or glycine-deficient diets during gestation. Leucine deprivation
      produced the most pronounced effect, with a 63% reduction in the expected number
      of viable neonatal mice. Cultured embryonic stem cells derived from Gcn2(-/-)
      mice failed to show the normal induction of eIF2alpha phosphorylation in cells
      deprived of leucine. To assess the biochemical effects of the loss of GCN2 in the
      whole animal, liver perfusion experiments were conducted. Histidine limitation in
      the presence of histidinol induced a twofold increase in the phosphorylation of
      eIF2alpha and a concomitant reduction in eIF2B activity in perfused livers from
      wild-type mice, but no changes in livers from Gcn2(-/-) mice.

PMID- 12215526
TI  - DNA methylation has a local effect on transcription and histone acetylation.
AB  - DNA methylation is commonly associated with gene silencing, and a link between
      histone deacetylation and DNA methylation has been established. However, the
      transcriptional impact of the position and length of methylated zones relative to
      the promoter and the coding region of a gene remains quite unclear. This study
      investigates the impact of regional methylation on transcription and the
      relationship between DNA methylation and histone acetylation. Using patch
      methylated stable episomes in human cells, we establish the pivotal importance of
      the location of DNA methylation in the regulation of transcription. We further
      demonstrate that the size of the methylated patch is not a key determinant for
      transcriptional suppression. The impact of DNA methylation on transcription is
      greater when it is in the transcription unit, and it is primarily a local effect.
      However, methylation outside of the transcription unit may potentiate the effect
      of methylation within the transcription unit. Acetylated histones are associated
      with unmethylated DNA and are nearly absent from methylated DNA regions. This
      association appears to be local and does not propagate along the DNA.

PMID- 12215527
TI  - Core promoter-dependent TFIIB conformation and a role for TFIIB conformation in
      transcription start site selection.
AB  - The general transcription factor TFIIB plays a central role in the selection of
      the transcription initiation site. The mechanisms involved are not clear,
      however. In this study, we analyze core promoter features that are responsible
      for the susceptibility to mutations in TFIIB and cause a shift in the
      transcription start site. We show that TFIIB can modulate both the 5' and 3'
      parameters of transcription start site selection in a manner dependent upon the
      sequence of the initiator. Mutations in TFIIB that cause aberrant transcription
      start site selection concentrate in a region that plays a pivotal role in
      modulating TFIIB conformation. Using epitope-specific antibody probes, we show
      that a TFIIB mutant that causes aberrant transcription start site selection
      assembles at the promoter in a conformation different from that for wild-type
      TFIIB. In addition, we uncover a core promoter-dependent effect on TFIIB
      conformation and provide evidence for novel sequence-specific TFIIB promoter
      contacts.

PMID- 12215528
TI  - In vivo kinetics of mRNA splicing and transport in mammalian cells.
AB  - The kinetics of pre-mRNA processing in living cells is poorly known, preventing a
      detailed analysis of the regulation of these reactions. Using tetracycline
      regulated promoters we performed, during a transcriptional induction, a complete
      analysis of the maturation of two cellular mRNAs, those for LT-alpha and beta
      globin. In both cases, splicing was appropriately described by first-order
      reactions with corresponding half-lives ranging between 0.4 and 7.5 min,
      depending on the intron. Transport also behaved as a first-order reaction during
      the early phase of beta-globin expression, with a nuclear dwelling time of 4 min.
      At a later time, analysis was prevented by the progressive accumulation within
      the nucleus of mature mRNA not directly involved in export. Our results further
      establish for these genes that (i) splicing components are never limiting, even
      when expression is induced in naive cells, (ii) there is no significant RNA
      degradation during splicing and transport, and (iii) precursor-to-product ratios
      at steady state can be used for the determination of splicing rates. Finally, the
      comparison between the kinetics of splicing during transcriptional induction and
      during transcriptional shutoff reveals a novel coupling between transcription and
      splicing.

PMID- 12215529
TI  - Cdc42/Rac1-mediated activation primes PAK2 for superactivation by tyrosine
      phosphorylation.
AB  - The involvement of p21-activated kinases (PAKs) in important cellular processes
      such as regulation of the actin skeleton morphology, transduction of signals
      controlling gene expression, and execution of programmed cell death has directed
      attention to the regulation of the activity of these kinases. Here we report that
      activation of PAK2 by p21 GTPases can be strongly potentiated by cellular
      tyrosine kinases. PAK2 became tyrosine phosphorylated in its N-terminal
      regulatory domain, where Y130 was identified as the major phosphoacceptor site.
      Tyrosine phosphorylation-mediated superactivation of PAK2 could be induced by
      overexpression of different Src kinases or by inhibiting cellular tyrosine
      phosphatases with pervanadate and could be blocked by the Src kinase inhibitor
      PP1 or by mutating the Y130 residue. Analysis of PAK2 mutants activated by amino
      acid changes in the autoinhibitory domain or the catalytic domain indicated that
      GTPase-induced conformational changes, rather than catalytic activation per se,
      rendered PAK2 a target for tyrosine phosphorylation. Thus, PAK activation
      represents a potentially important point of convergence of tyrosine kinase- and
      p21 GTPase-dependent signaling pathways.

PMID- 12215530
TI  - Recognition of RNA editing sites is directed by unique proteins in chloroplasts:
      biochemical identification of cis-acting elements and trans-acting factors
      involved in RNA editing in tobacco and pea chloroplasts.
AB  - RNA editing in higher-plant chloroplasts involves C-to-U conversions at specific
      sites. Although in vivo analyses have been performed, little is known about the
      biochemical aspects of chloroplast editing reactions. Here we improved our
      original in vitro system and devised a procedure for preparing active chloroplast
      extracts not only from tobacco plants but also from pea plants. Using our tobacco
      in vitro system, cis-acting elements were defined for psbE and petB mRNAs.
      Distinct proteins were found to bind specifically to each cis-element, a 56-kDa
      protein to the psbE site and a 70-kDa species to the petB site. Pea chloroplasts
      lack the corresponding editing site in psbE since T is already present in the
      DNA. Parallel in vitro analyses with tobacco and pea extracts revealed that the
      pea plant has no editing activity for psbE mRNAs and lacks the 56-kDa protein,
      whereas petB mRNAs are edited and the 70-kDa protein is also present. Therefore,
      coevolution of an editing site and its cognate trans-factor was demonstrated
      biochemically in psbE mRNA editing between tobacco and pea plants.

PMID- 12215531
TI  - The Ccr4-not complex and yTAF1 (yTaf(II)130p/yTaf(II)145p) show physical and
      functional interactions.
AB  - The Saccharomyces cerevisiae Ccr4-Not complex is a global regulator of
      transcription that is thought to regulate TATA binding protein (TBP) function at
      certain promoters specifically. In this paper, we show interactions between the
      essential domain of Not1p, which interacts with Not4p and Not5p, and the N
      terminal domain of yTAF1. We isolated a temperature-sensitive nonsense allele of
      TAF1, taf1-4, which is synthetically lethal at the permissive temperature when
      combined with not4 and not5 mutants and which produces high levels of a C
      terminally truncated yTAF1 derivative. Overexpression of C-terminally truncated
      yTAF1 is toxic in not4 or not5 mutants, whereas overexpression of full-length
      yTAF1 suppresses not4. Furthermore, mutations in the autoinhibitory N-terminal
      TAND domain of yTAF1 suppress not5, and the overexpression of similar mutants
      does not suppress not4. We find that, like Not5p, yTAF1 acts as a repressor of
      stress response element-dependent transcription. Finally, we have evidence for
      stress-regulated occupancy of promoter DNA by Not5p and for Not5p-dependent
      regulation of yTAF1 association with promoter DNA. Taken together with our
      finding that Not1p copurifies with glutathione S-transferase-yTaf1 in large
      complexes, these results provide the first molecular evidence that the Ccr4-Not
      complex might interact with yTAF1 to regulate its association at promoters, a
      function that might in turn regulate the autoinhibitory N-terminal domain of
      yTAF1.

PMID- 12215532
TI  - Activation of the Bur1-Bur2 cyclin-dependent kinase complex by Cak1.
AB  - Cyclin-dependent kinases (Cdks) were originally identified as regulators of
      eukaryotic cell cycle progression, but several Cdks were subsequently shown to
      perform important roles as transcriptional regulators. While the mechanisms
      regulating the Cdks involved in cell cycle progression are well documented, much
      less is known regarding how the Cdks that are involved in transcription are
      regulated. In Saccharomyces cerevisiae, Bur1 and Bur2 comprise a Cdk complex that
      is involved in transcriptional regulation, presumably mediated by its
      phosphorylation of the carboxy-terminal domain (CTD) of the largest subunit of
      RNA polymerase II. To investigate the regulation of Bur1 in vivo, we searched for
      high-copy-number suppressors of a bur1 temperature-sensitive mutation,
      identifying a single gene, CAK1. Cak1 is known to activate two other Cdks in
      yeast by phosphorylating a threonine within their conserved T-loop domains. Bur1
      also has the conserved threonine within its T loop and is therefore a potential
      direct target of Cak1. Additional tests establish a direct functional interaction
      between Cak1 and the Bur1-Bur2 Cdk complex: Bur1 is phosphorylated in vivo, both
      the conserved Bur1 T-loop threonine and Cak1 are required for phosphorylation and
      Bur1 function in vivo, and recombinant Cak1 stimulates CTD kinase activity of the
      purified Bur1-Bur2 complex in vitro. Thus, both genetic and biochemical evidence
      demonstrate that Cak1 is a physiological regulator of the Bur1 kinase.

PMID- 12215533
TI  - Molecular interaction and synergistic activation of a promoter by Six, Eya, and
      Dach proteins mediated through CREB binding protein.
AB  - Drosophila sine oculis, eyes absent, and dachshund are essential for compound eye
      formation and form a gene network with direct protein interaction and genetic
      regulation. The vertebrate homologues of these genes, Six, Eya, and Dach, also
      form a similar genetic network during muscle formation. To elucidate the
      molecular mechanism underlying the network among Six, Eya, and Dach, we examined
      the molecular interactions among the encoded proteins. Eya interacted directly
      with Six but never with Dach. Dach transactivated a multimerized GAL4 reporter
      gene by coproduction of GAL4-Eya fusion proteins. Transactivation by Eya and Dach
      was repressed by overexpression of VP16 or E1A but not by E1A mutation, which is
      defective for CREB binding protein (CBP) binding. Recruitment of CBP to the
      immobilized chromatin DNA template was dependent on FLAG-Dach and GAL4-Eya3.
      These results indicate that CBP is a mediator of the interaction between Eya and
      Dach. Contrary to our expectations, Dach binds to chromatin DNA by itself, not
      being tethered by GAL4-Eya3. Dach also binds to naked DNA with lower affinity.
      The conserved DD1 domain is responsible for binding to DNA. Transactivation was
      also observed by coproduction of GAL4-Six, Eya, and Dach, indicating that Eya and
      Dach synergy is relevant when Eya is tethered to DNA through Six protein. Our
      results demonstrated that synergy is mediated through direct interaction of Six
      Eya and through the interaction of Eya-Dach with CBP and explain the molecular
      basis for the genetic interactions among Six, Eya, and Dach. This work provides
      fundamental information on the role and the mechanism of action of this gene
      cassette in tissue differentiation and organogenesis.

PMID- 12215534
TI  - Inactivation of the retinoblastoma protein family can bypass the HCF-1 defect in
      tsBN67 cell proliferation and cytokinesis.
AB  - Owing to a single missense mutation in the cell proliferation factor HCF-1, the
      temperature-sensitive tsBN67 hamster cell line arrests proliferation at
      nonpermissive temperatures, primarily in a G(0)/G(1) state, and displays
      temperature-sensitive cytokinesis defects. The HCF-1 mutation in tsBN67 cells
      also causes a temperature-sensitive dissociation of HCF-1 from chromatin prior to
      cell proliferation arrest, suggesting that HCF-1-chromatin association is
      important for mammalian-cell proliferation. Here, we report that the simian virus
      40 (SV40) early region, in particular, large T antigen (Tag), and the adenovirus
      oncoprotein E1A can rescue the tsBN67 cell proliferation defect at nonpermissive
      temperatures. The SV40 early region rescues the tsBN67 cell proliferation defect
      without restoring the HCF-1-chromatin association, indicating that these
      oncoproteins bypass a requirement for HCF-1 function. The SV40 early region also
      rescues the tsBN67 cytokinesis defect, suggesting that the roles of HCF-1 in cell
      proliferation and proper cytokinesis are intimately linked. The ability of SV40
      Tag and adenovirus E1A to inactivate members of the pRb protein family-pRb, p107,
      and p130-is important for the bypass of HCF-1 function. These results suggest
      that HCF-1 regulates mammalian-cell proliferation and cytokinesis, at least in
      part, by either directly or indirectly opposing pRb family member function.

PMID- 12215535
TI  - The SWI/SNF chromatin-remodeling factor stimulates repair by human excision
      nuclease in the mononucleosome core particle.
AB  - To investigate the role of chromatin remodeling in nucleotide excision repair, we
      prepared mononucleosomes with a 200-bp duplex containing an acetylaminofluorene
      guanine (AAF-G) adduct at a single site. DNase I footprinting revealed a well
      phased nucleosome structure with the AAF-G adduct near the center of twofold
      symmetry of the nucleosome core. This mononucleosome substrate was used to
      examine the effect of the SWI/SNF remodeling complex on the activity of human
      excision nuclease reconstituted from six purified excision repair factors. We
      found that the three repair factors implicated in damage recognition, RPA, XPA,
      and XPC, stimulate the remodeling activity of SWI/SNF, which in turn stimulates
      the removal of the AAF-G adduct from the nucleosome core by the excision
      nuclease. This is the first demonstration of the stimulation of nucleotide
      excision repair of a lesion in the nucleosome core by a chromatin-remodeling
      factor and contrasts with the ACF remodeling factor, which stimulates the removal
      of lesions from internucleosomal linker regions but not from the nucleosome core.

PMID- 12215536
TI  - Nuclear targeting by the growth factor midkine.
AB  - Ligand-receptor internalization has been traditionally regarded as part of the
      cellular desensitization system. Low-density lipoprotein receptor-related protein
      (LRP) is a large endocytosis receptor with a diverse array of ligands. We
      recently showed that LRP binds heparin-binding growth factor midkine. Here we
      demonstrate that LRP mediates nuclear targeting by midkine and that the nuclear
      targeting is biologically important. Exogenous midkine reached the nucleus, where
      intact midkine was detected, within 20 min. Midkine was not internalized in LRP
      deficient cells, whereas transfection of an LRP expression vector restored
      midkine internalization and subsequent nuclear translocation. Internalized
      midkine in the cytoplasm bound to nucleolin, a nucleocytoplasmic shuttle protein.
      The midkine-binding sites were mapped to acidic stretches in the N-terminal
      domain of nucleolin. When the nuclear localization signal located next to the
      acidic stretches was deleted, we found that the mutant nucleolin not only
      accumulated in the cytoplasm but also suppressed the nuclear translocation of
      midkine. By using cells that overexpressed the mutant nucleolin, we further
      demonstrated that the nuclear targeting was necessary for the full activity of
      midkine in the promotion of cell survival. This study therefore reveals a novel
      role of LRP in intracellular signaling by its ligand and the importance of
      nucleolin in this process.

PMID- 12215537
TI  - Efficient specific DNA binding by p53 requires both its central and C-terminal
      domains as revealed by studies with high-mobility group 1 protein.
AB  - The nonhistone chromosomal protein high-mobility group 1 protein (HMG-1/HMGB1)
      can serve as an activator of p53 sequence-specific DNA binding (L. Jayaraman, N.
      C. Moorthy, K. G. Murthy, J. L. Manley, M. Bustin, and C. Prives, Genes Dev.
      12:462-472, 1998). HMGB1 is capable of interacting with DNA in a non-sequence
      specific manner and causes a significant bend in the DNA helix. Since p53
      requires a significant bend in the target site, we examined whether DNA bending
      by HMGB1 may be involved in its enhancement of p53 sequence-specific binding.
      Accordingly, a 66-bp oligonucleonucleotide containing a p53 binding site was
      locked in a bent conformation by ligating its ends to form a microcircle. Indeed,
      p53 had a dramatically greater affinity for the microcircle than for the linear
      66-bp DNA. Moreover, HMGB1 augmented binding to the linear DNA but not to the
      microcircle, suggesting that HMGB1 works by providing prebent DNA to p53. p53
      contains a central core sequence-specific DNA binding region and a C-terminal
      region that recognizes various forms of DNA non-sequence specifically. The p53 C
      terminus has also been shown to serve as an autoinhibitor of core-DNA
      interactions. Remarkably, although the p53 C terminus inhibited p53 binding to
      the linear DNA, it was required for the increased affinity of p53 for the
      microcircle. Thus, depending on the DNA structure, the p53 C terminus can serve
      as a negative or a positive regulator of p53 binding to the same sequence and
      length of DNA. We propose that both DNA binding domains of p53 cooperate to
      recognize sequence and structure in genomic DNA and that HMGB1 can help to
      provide the optimal DNA structure for p53.

PMID- 12215538
TI  - Mitotic phosphorylation of chromosomal protein HMGN1 inhibits nuclear import and
      promotes interaction with 14.3.3 proteins.
AB  - Progression through mitosis is associated with reversible phosphorylation of many
      nuclear proteins including that of the high-mobility group N (HMGN) nucleosomal
      binding protein family. Here we use immunofluorescence and in vitro nuclear
      import studies to demonstrate that mitotic phosphorylation of the nucleosomal
      binding domain (NBD) of the HMGN1 protein prevents its reentry into the newly
      formed nucleus in late telophase. By microinjecting wild-type and mutant proteins
      into the cytoplasm of HeLa cells and expressing these proteins in HmgN1(-/-)
      cells, we demonstrate that the inability to enter the nucleus is a consequence of
      phosphorylation and is not due to the presence of negative charges. Using
      affinity chromatography with recombinant proteins and nuclear extracts prepared
      from logarithmically growing or mitotically arrested cells, we demonstrate that
      phosphorylation of the NBD of HMGN1 promotes interaction with specific 14.3.3
      isotypes. We conclude that mitotic phosphorylation of HMGN1 protein promotes
      interaction with 14.3.3 proteins and suggest that this interaction impedes the
      reentry of the proteins into the nucleus during telophase. Taken together with
      the results of previous studies, our results suggest a dual role for mitotic
      phosphorylation of HMGN1: abolishment of chromatin binding and inhibition of
      nuclear import.

PMID- 12215539
TI  - Gene structure and functional analysis of the mouse nidogen-2 gene: nidogen-2 is
      not essential for basement membrane formation in mice.
AB  - Nidogens are highly conserved proteins in vertebrates and invertebrates and are
      found in almost all basement membranes. According to the classical hypothesis of
      basement membrane organization, nidogens connect the laminin and collagen IV
      networks, so stabilizing the basement membrane, and integrate other proteins. In
      mammals two nidogen proteins, nidogen-1 and nidogen-2, have been discovered.
      Nidogen-2 is typically enriched in endothelial basement membranes, whereas
      nidogen-1 shows broader localization in most basement membranes. Surprisingly,
      analysis of nidogen-1 gene knockout mice presented evidence that nidogen-1 is not
      essential for basement membrane formation and may be compensated for by nidogen
      2. In order to assess the structure and in vivo function of the nidogen-2 gene in
      mice, we cloned the gene and determined its structure and chromosomal location.
      Next we analyzed mice carrying an insertional mutation in the nidogen-2 gene that
      was generated by the secretory gene trap approach. Our molecular and biochemical
      characterization identified the mutation as a phenotypic null allele. Nidogen-2
      deficient mice show no overt abnormalities and are fertile, and basement
      membranes appear normal by ultrastructural analysis and immunostaining. Nidogen-2
      deficiency does not lead to hemorrhages in mice as one may have expected. Our
      results show that nidogen-2 is not essential for basement membrane formation or
      maintenance.

PMID- 12215540
TI  - Novel mechanism of nuclear receptor corepressor interaction dictated by
      activation function 2 helix determinants.
AB  - Transcriptional regulation by nuclear receptors is controlled by the concerted
      action of coactivator and corepressor proteins. The product of the thyroid
      hormone-regulated mammalian gene hairless (Hr) was recently shown to function as
      a thyroid hormone receptor corepressor. Here we report that Hr acts as a potent
      repressor of transcriptional activation by RORalpha, an orphan nuclear receptor
      essential for cerebellar development. In contrast to other corepressor-nuclear
      receptor interactions, Hr binding to RORalpha is mediated by two LXXLL-containing
      motifs, a mechanism associated with coactivator interaction. Mutagenesis of
      conserved amino acids in the ligand binding domain indicates that RORalpha
      activity is ligand-dependent, suggesting that corepressor activity is maintained
      in the presence of ligand. Despite similar recognition helices shared with
      coactivators, Hr does not compete for the same molecular determinants at the
      surface of the RORalpha ligand binding domain, indicating that Hr-mediated
      repression is not simply through displacement of coactivators. Remarkably, the
      specificity of Hr corepressor action can be transferred to a retinoic acid
      receptor by exchanging the activation function 2 (AF-2) helix. Repression of the
      chimeric receptor is observed in the presence of retinoic acid, demonstrating
      that in this context, Hr is indeed a ligand-oblivious nuclear receptor
      corepressor. These results suggest a novel molecular mechanism for corepressor
      action and demonstrate that the AF-2 helix can play a dynamic role in controlling
      corepressor as well as coactivator interactions. The interaction of Hr with
      RORalpha provides direct evidence for the convergence of thyroid hormone and
      RORalpha-mediated pathways in cerebellar development.

PMID- 12215541
TI  - Control of the hypoxic response in Drosophila melanogaster by the basic helix
      loop-helix PAS protein similar.
AB  - In mammalian systems, the heterodimeric basic helix-loop-helix (bHLH)-PAS
      transcription hypoxia-inducible factor (HIF) has emerged as the key regulator of
      responses to hypoxia. Here we define a homologous system in Drosophila
      melanogaster, and we characterize its activity in vivo during development. By
      using transcriptional reporters in developing transgenic flies, we show that
      hypoxia-inducible activity rises to a peak in late embryogenesis and is most
      pronounced in tracheal cells. We show that the bHLH-PAS proteins Similar (Sima)
      and Tango (Tgo) function as HIF-alpha and HIF-beta homologues, respectively, and
      demonstrate a conserved mode of regulation for Sima by oxygen. Sima protein, but
      not its mRNA, was upregulated in hypoxia. Time course experiments following
      pulsed ectopic expression demonstrated that Sima is stabilized in hypoxia and
      that degradation relies on a central domain encompassing amino acids 692 to 863.
      Continuous ectopic expression overrode Sima degradation, which remained
      cytoplasmic in normoxia, and translocated to the nucleus only in hypoxia,
      revealing a second oxygen-regulated activation step. Abrogation of the Drosophila
      Egl-9 prolyl hydroxylase homologue, CG1114, caused both stabilization and nuclear
      localization of Sima, indicating a central involvement in both processes. Tight
      conservation of the HIF/prolyl hydroxylase system in Drosophila provides a new
      focus for understanding oxygen homeostasis in intact multicellular organisms.

PMID- 12215542
TI  - Phyllopod acts as an adaptor protein to link the sina ubiquitin ligase to the
      substrate protein tramtrack.
AB  - The RING domain protein Sina, together with Phyllopod and the F-box protein Ebi,
      forms a Ras-regulated E3 ubiquitin ligase complex that activates photoreceptor
      cell differentiation in the eye of Drosophila melanogaster. The expression of
      Phyllopod is induced upon Ras activation, allowing the complex to degrade the
      transcription repressor Tramtrack and removing its block of neuronal development
      in photoreceptor precursors. We show that Phyllopod functions as an adaptor in
      the complex, physically linking Sina with Tramtrack via separate binding domains.
      One 19-amino-acid domain in Phyllopod interacts with a region of Sina's SBD
      domain. Another domain in Phyllopod interacts with a C-terminal helix in the POZ
      domain of Tramtrack. This interaction is specific to the Tramtrack POZ domain and
      not to other POZ domain proteins present in photoreceptor precursors. Degradation
      of Tramtrack is dependent upon association of Sina with its cognate binding site
      in Phyllopod. These results illustrate how Ras signaling can modulate an E3
      ligase activity not by the phosphorylation of substrate proteins but by
      regulating the expression of specific E3 adaptors.

PMID- 12215543
TI  - Murine ovarian development is not affected by inactivation of the bcl-2 family
      member diva.
AB  - Diva (also called Boo/Bcl-B) is a member of the Bcl-2 gene family and most likely
      functions during apoptosis. Diva is highly expressed in the ovary, and both pro-
      and antiapoptotic functions have been ascribed to this protein. To determine the
      role of Diva during murine development, we used gene targeting to inactivate
      DIVA: The Diva-null mice are born at the expected ratios, are fertile, and have
      no obvious histological abnormalities, and long-term survival did not differ from
      littermate controls. Additionally, Diva was not required for apoptosis occurring
      from genotoxic insult in the ovaries or other organs. Thus, Diva is not critical
      for the normal development of the ovaries, or in its absence its function is
      subserved by another protein.

PMID- 12215544
TI  - Nuclear export and retention signals in the RS domain of SR proteins.
AB  - Splicing factors of the SR protein family share a modular structure consisting of
      one or two RNA recognition motifs (RRMs) and a C-terminal RS domain rich in
      arginine and serine residues. The RS domain, which is extensively phosphorylated,
      promotes protein-protein interactions and directs subcellular localization and-in
      certain situations-nucleocytoplasmic shuttling of individual SR proteins. We
      analyzed mutant versions of human SF2/ASF in which the natural RS repeats were
      replaced by RD or RE repeats and compared the splicing and subcellular
      localization properties of these proteins to those of SF2/ASF lacking the entire
      RS domain or possessing a minimal RS domain consisting of 10 consecutive RS
      dipeptides (RS10). In vitro splicing of a pre-mRNA that requires an RS domain
      could take place when the mutant RD, RE, or RS10 domain replaced the natural
      domain. The RS10 version of SF2/ASF shuttled between the nucleus and the
      cytoplasm in the same manner as the wild-type protein, suggesting that a tract of
      consecutive RS dipeptides, in conjunction with the RRMs of SF2/ASF, is necessary
      and sufficient to direct nucleocytoplasmic shuttling. However, the SR protein
      SC35 has two long stretches of RS repeats, yet it is not a shuttling protein. We
      demonstrate the presence of a dominant nuclear retention signal in the RS domain
      of SC35.

PMID- 12215545
TI  - NRC-interacting factor 1 is a novel cotransducer that interacts with and
      regulates the activity of the nuclear hormone receptor coactivator NRC.
AB  - We previously reported the cloning and characterization of a novel nuclear
      hormone receptor transcriptional coactivator, which we refer to as NRC. NRC is a
      2,063-amino-acid nuclear protein which contains a potent N-terminal activation
      domain and several C-terminal modules which interact with CBP and ligand-bound
      nuclear hormone receptors as well as c-Fos and c-Jun. In this study we sought to
      clone and identify novel factors that interact with NRC to modulate its
      transcriptional activity. Here we describe the cloning and characterization of a
      novel protein we refer to as NIF-1 (NRC-interacting factor 1). NIF-1 was cloned
      from rat pituitary and human cell lines and was found to interact in vivo and in
      vitro with NRC. NIF-1 is a 1,342-amino-acid nuclear protein containing a number
      of conserved domains, including six Cys-2/His-2 zinc fingers, an N-terminal
      stretch of acidic amino acids, and a C-terminal leucine zipper-like motif. Zinc
      fingers 1 to 3 are potential DNA-binding BED finger domains recently proposed to
      play a role in altering local chromatin architecture. We mapped the interaction
      domains of NRC and NIF-1. Although NIF-1 does not directly interact with nuclear
      receptors, it markedly enhances ligand-dependent transcriptional activation by
      nuclear hormone receptors in vivo as well as activation by c-Fos and c-Jun. These
      results, and the finding that NIF-1 interacts with NRC in vivo, suggest that NIF
      1 functions to regulate transcriptional activation through NRC. We suggest that
      NIF-1, and factors which associate with coactivators but not receptors, be
      referred to as cotransducers, which act in vivo either as part of a coactivator
      complex or downstream of a coactivator complex to modulate transcriptional
      activity. Our findings suggest that NIF-1 may be a functional component of an NRC
      complex and acts as a regulator or cotransducer of NRC function.

PMID- 12215546
TI  - RhoGEF specificity mutants implicate RhoA as a target for Dbs transforming
      activity.
AB  - Dbs is a Rho-specific guanine nucleotide exchange factor (RhoGEF) that exhibits
      transforming activity when overexpressed in NIH 3T3 mouse fibroblasts. Like many
      RhoGEFs, the in vitro catalytic activity of Dbs is not limited to a single
      substrate. It can catalyze the exchange of GDP for GTP on RhoA and Cdc42, both of
      which are expressed in most cell types. This lack of substrate specificity, which
      is relatively common among members of the RhoGEF family, complicates efforts to
      determine the molecular basis of their transforming activity. We have recently
      determined crystal structures of several RhoGEFs bound to their cognate GTPases
      and have used these complexes to predict structural determinants dictating the
      specificities of coupling between RhoGEFs and GTPases. Guided by this
      information, we mutated Dbs to alter significantly its relative exchange activity
      for RhoA versus Cdc42 and show that the transformation potential of Dbs
      correlates with exchange on RhoA but not Cdc42. Supporting this conclusion,
      oncogenic Dbs activates endogenous RhoA but not endogenous Cdc42 in NIH 3T3
      cells. Similarly, a competitive inhibitor that blocks RhoA activation also blocks
      Dbs-mediated transformation. In conclusion, this study highlights the usefulness
      of specificity mutants of RhoGEFs as tools to genetically dissect the multiple
      signaling pathways potentially activated by overexpressed or oncogenic RhoGEFs.
      These ideas are exemplified for Dbs, which is strongly implicated in the
      transformation of NIH 3T3 cells via RhoA and not Cdc42.

PMID- 12215547
TI  - Bni5p, a septin-interacting protein, is required for normal septin function and
      cytokinesis in Saccharomyces cerevisiae.
AB  - In the budding yeast Saccharomyces cerevisiae, the Cdc3p, Cdc10p, Cdc11p, Cdc12p,
      and Sep7p/Shs1p septins assemble early in the cell cycle in a ring that marks the
      future cytokinetic site. The septins appear to be major structural components of
      a set of filaments at the mother-bud neck and function as a scaffold for
      recruiting proteins involved in cytokinesis and other processes. We isolated a
      novel gene, BNI5, as a dosage suppressor of the cdc12-6 growth defect.
      Overexpression of BNI5 also suppressed the growth defects of cdc10-1, cdc11-6,
      and sep7Delta strains. Loss of BNI5 resulted in a cytokinesis defect, as
      evidenced by the formation of connected cells with shared cytoplasms, and
      deletion of BNI5 in a cdc3-6, cdc10-1, cdc11-6, cdc12-6, or sep7Delta mutant
      strain resulted in enhanced defects in septin localization and cytokinesis. Bni5p
      localizes to the mother-bud neck in a septin-dependent manner shortly after bud
      emergence and disappears from the neck approximately 2 to 3 min before spindle
      disassembly. Two-hybrid, in vitro binding, and protein-localization studies
      suggest that Bni5p interacts with the N-terminal domain of Cdc11p, which also
      appears to be sufficient for the localization of Cdc11p, its interaction with
      other septins, and other critical aspects of its function. Our data suggest that
      the Bni5p-septin interaction is important for septin ring stability and function,
      which is in turn critical for normal cytokinesis.

PMID- 12215548
TI  - Characterization of lpa(2) (Edg4) and lpa(1)/lpa(2) (Edg2/Edg4) lysophosphatidic
      acid receptor knockout mice: signaling deficits without obvious phenotypic
      abnormality attributable to lpa(2).
AB  - Lysophosphatidic acid (LPA), a bioactive lipid produced by several cell types
      including postmitotic neurons and activated platelets, is thought to be involved
      in various biological processes, including brain development. Three cognate G
      protein-coupled receptors encoded by lpa(1)/lp(A1)/Edg-2/Gpcr26,
      lpa(2)/lp(A2)/Edg-4, and lpa(3)/lp(A3)/Edg-7 mediate the cellular effects of LPA.
      We have previously shown that deletion of lpa(1) in mice results in craniofacial
      dysmorphism, semilethality due to defective suckling behavior, and generation of
      a small fraction of pups with frontal hematoma. To further investigate the role
      of these receptors and LPA signaling in the organism, we deleted lpa(2) in mice.
      Homozygous knockout (lpa(2)((-/-))) mice were born at the expected frequency and
      displayed no obvious phenotypic abnormalities. Intercrosses allowed generation of
      lpa(1)((-/-)) lpa(2)((-/-)) double knockout mice, which displayed no additional
      phenotypic abnormalities relative to lpa(1)((-/-)) mice except for an increased
      incidence of perinatal frontal hematoma. Histological analyses of lpa(1)((-/-))
      lpa(2)((-/-)) embryonic cerebral cortices did not reveal obvious differences in
      the proliferating cell population. However, many LPA-induced responses, including
      phospholipase C activation, Ca(2+) mobilization, adenylyl cyclase activation,
      proliferation, JNK activation, Akt activation, and stress fiber formation, were
      absent or severely reduced in embryonic fibroblasts derived from lpa(1)((-/-))
      lpa(2)((-/-)) mice. Except for adenylyl cyclase activation [which was nearly
      abolished in lpa(1)((-/-)) fibroblasts], these responses were only partially
      affected in lpa(1)((-/-)) and lpa(2)((-/-)) fibroblasts. Thus, although LPA(2) is
      not essential for normal mouse development, it does act redundantly with LPA(1)
      to mediate most LPA responses in fibroblasts.

PMID- 12215549
TI  - Combined functional and structural evaluation of cancer patients with a hybrid
      camera-based PET/CT system using (18)F-FDG.
AB  - Correct diagnosis and definition of the functional and anatomic status of lesions
      in cancer patients are of clinical importance. The value of hybrid imaging using
      a gamma camera-based PET/CT and (18)F-FDG in determining the relationship between
      mass and cancer was assessed. METHODS: Hybrid imaging was performed using a
      device combining low-dose CT and gamma camera-based PET. Ninety-one patients with
      histologically proven malignancy and 190 suspected sites of disease were
      evaluated. Camera-based PET was performed after the injection of 296-370 MBq
      (18)F-FDG. The presence of organomegaly or an abnormal mass on CT and of abnormal
      uptake of (18)F-FDG was assessed for each suspected lesion. The presence of
      malignancy at each site was determined by biopsy, imaging follow-up, or clinical
      outcome. RESULTS: Five imaging patterns were found. Pattern 1 showed congruent
      abnormal (18)F-FDG uptake and a mass on CT in 110 of the lesions. One hundred two
      sites (93%) had active cancer. Pattern 2 showed a mass on CT, larger than the
      area of abnormal (18)F-FDG uptake, and was found in 5 lesions. Active malignancy
      was proven in 3 sites (60%). Pattern 3 showed an abnormal mass on CT with no
      (18)F-FDG uptake and was found in 52 lesions. Thirteen of these lesions (25%) had
      active tumor. Pattern 4 showing abnormal (18)F-FDG uptake with no mass on CT was
      found in 23 lesions. Sixteen of these sites (70%) were malignant. Pattern 5
      showed normal CT findings and no abnormal (18)F-FDG uptake in 11 patients. Two of
      these patients (18%) had active disease. Hybrid imaging was of value in
      establishing the correct relationship between CT and (18)F-FDG findings in 98 of
      the 190 lesions (52%). CONCLUSION: A range of patterns presenting with or without
      abnormal (18)F-FDG uptake on camera-based PET and a mass on CT may occur in
      suspected cancer sites. Both structural changes on CT and increased cell
      metabolism expressed by abnormal (18)F-FDG uptake should be considered in
      oncologic imaging. Hybrid imaging, a combined physiologic and anatomic modality,
      appears to provide new diagnostic opportunities in characterizing function and
      morphology in malignancies.

PMID- 12215550
TI  - PET/CT: comparison of quantitative tracer uptake between germanium and CT
      transmission attenuation-corrected images.
AB  - In PET, transmission scanning for attenuation correction has most commonly been
      performed with an external positron-emitting radionuclide source, such as (68)Ge.
      More recently, combined PET/CT scanners have been developed in which the CT data
      can be used for both anatometabolic image formation and attenuation correction of
      the PET data. The purpose of this study was to assess the quantitative
      differences between CT-based and germanium-based attenuation-corrected PET
      images. METHODS: Twenty-eight patients with known or suspected cancer underwent
      whole-body (18)F-FDG PET/CT scanning for clinical diagnostic purposes. For each
      patient, attenuation maps were obtained from both the CT scan and the (68)Ge
      transmission data, and 2 different attenuation-corrected emission datasets were
      produced. Measured activity concentrations (both mean and maximum) from identical
      regions of interest in representative normal organs and in 36 pathologic foci of
      uptake were compared. RESULTS: CT-corrected emission images generally showed
      slightly higher radioactive concentration values than did germanium-corrected
      images (P < 0.01) for all lesions and all normal organs except the lung. Mean and
      maximum radioactivity concentrations were 4.3%-15.2% higher for CT-corrected
      images than for germanium-corrected images. Calculated radioactivity
      concentrations were significantly greater in osseous lesions than in nonosseous
      lesions (11.0% vs. 2.3%, P < 0.05, for mean value; 11.1% vs. 2.1%, P < 0.01, for
      maximum value). A weak positive correlation was observed between the CT
      Hounsfield units within the regions of interest and the percentage difference in
      apparent tracer activity in the CT-corrected images. CONCLUSION: Although
      quantitative radioactivity values are generally comparable between CT- and
      germanium-corrected emission PET images, CT-based attenuation correction produced
      radioactivity concentration values significantly higher than the germanium-based
      corrected values. These effects, especially in radiodense tissues, should be
      noted when using and comparing quantitative PET analyses from PET and PET/CT
      systems.

PMID- 12215551
TI  - Assessment of malignant pleural mesothelioma with (18)F-FDG dual-head gamma
      camera coincidence imaging: comparison with histopathology.
AB  - Malignant pleural mesothelioma is an aggressive primary neoplasm for which early
      detection and accurate staging are known diagnostic challenges. The role of (18)F
      FDG dual-head gamma-camera coincidence imaging ((18)F-FDG-CI) is yet to be
      defined. The purpose of this study was to evaluate the usefulness of (18)F-FDG-CI
      in the assessment of malignant pleural mesothelioma using histopathology as the
      gold standard. METHODS: Fifteen consecutive patients with CT scan evidence of
      pleural thickening, fluid, plaques, or calcification underwent (18)F-FDG imaging
      1.5 h after the intravenous administration of 370 MBq (18)F-FDG. Imaging was
      performed with a dual-head gamma camera equipped with 2.54-cm-thick NaI crystals
      operating in coincidence mode. Using an iterative algorithm, whole-body images
      were reconstructed as transaxial, sagittal, and coronal images. No attenuation
      correction was applied. The results of (18)F-FDG-CI scans were compared with CT
      and with histopathologic diagnosis. RESULTS: Eleven of 15 patients had
      histologically proven malignant mesotheliomas (10 epithelial, 1 sarcomatoid). All
      11 primary tumors were detected by (18)F-FDG, and absence of disease was
      confirmed in the 4 patients who were disease free. Thirty-four lesions were
      biopsied; among these, 29 were found to be positive for tumor. (18)F-FDG was true
      positive in 28 lesions, true-negative in 4, false-negative in 1 (0.5 cm in
      diameter), and false-positive in 1 (inflammatory pleuritis). The smallest lesion
      detected was 0.8 cm. For biopsied lesions, overall sensitivity, specificity, and
      accuracy for (18)F-FDG-CI were 97%, 80%, and 94% respectively, compared with 83%,
      80%, and 82% for CT. Twenty-one of 29 positive lesions involved the pleura, lung
      parenchyma, or chest wall and were all (18)F-FDG avid. In the mediastinum, (18)F
      FDG-CI detected 7 of 8 biopsy-positive lesions (88%), whereas CT was positive in
      6 of 8 lesions (75%). (18)F-FDG identified extrathoracic metastases in 5
      patients, excluding them from surgical therapy. CONCLUSION: These preliminary
      results suggest that (18)F-FDG-CI appears to be an accurate method to diagnose
      and to define the extent of disease in patients with diffuse malignant pleural
      mesothelioma.

PMID- 12215552
TI  - The PLACORHEN study: a double-blind, placebo-controlled, randomized radionuclide
      study with (186)Re-etidronate in hormone-resistant prostate cancer patients with
      painful bone metastases. Placebo Controlled Rhenium Study.
AB  - (186)Re-1,1-hydroxyethylidene diphosphonate (etidronate) can be used for the
      palliative treatment of metastatic bone pain. A randomized, placebo-controlled
      study using (186)Re-etidronate was conducted on end-stage prostate cancer
      patients with metastatic bone pain. METHODS: Pain relief was assessed using an
      electronic diary containing questions reflecting the multidimensional character
      of chronic pain. The diary was marked twice daily for a maximum of 14 wk (2 wk
      before and 12 wk after the injection). Pain response was determined using a
      specific decision rule in which pain intensity, medication index, and daily
      activities were the core determinants. A positive response day was defined as a
      day on which pain intensity was reduced > or = 25% compared with baseline values,
      while medication index and daily activities were at least constant, or on which
      pain intensity was reduced < 25% and medication index or daily activities
      improved > or = 25%, without worsening of the remaining factor. The total
      response (%) was defined as the number of positive response days divided by the
      number of days of follow-up. RESULTS: Of the 111 included patients, 79 were
      evaluable (43 (186)Re-etidronate, 36 placebo). Thirty-two patients were excluded
      from the analysis because of incomplete datasets. The total response of the
      patients treated with (186)Re-etidronate varied from 0% to 96% (mean, 27%, or
      23/84 d). In the placebo group, the total response varied from 0% to 80% (mean,
      13%, or 11/84 d; Mann-Whitney U test, P < 0.05). The number of patients who
      requested radiotherapy was higher in the placebo group (67%) than in the (186)Re
      etidronate group (44%) (relative risk, 1.51; Fisher's exact test, P = 0.069).
      CONCLUSION: This randomized controlled trial confirmed that, compared with
      placebo, (186)Re-etidronate resulted in a significantly longer pain response in
      the treatment of bone pain from metastasized prostate cancer.

PMID- 12215553
TI  - The FDG lumped constant in normal human brain.
AB  - The lumped constant (LC) is a correction factor used to infer glucose metabolic
      rate (MR(glc)) from FDG metabolic rate (MR(FDG)). METHODS: LC was determined in
      normal brain in 10 subjects (4 male, 6 female) by measuring regional MR(glc) and
      MR(FDG) independently using 1-(11)C-glucose and (18)F-FDG with dynamic positron
      tomographic imaging, arterial blood sampling, and region-of-interest time
      activity curve analysis with appropriate compartmental models. RESULTS: The mean
      LC (+/-SD) for normal brain was found to be 0.89 +/- 0.08. The value for
      cerebellum was slightly lower, 0.78 +/- 0.11 (P = 0.006; 2-tailed paired t test).
      CONCLUSION: The LC values determined in this study are considerably higher than
      older values in the literature, probably because of methodologic differences, but
      agree with a recent study by Hasselbalch.

PMID- 12215554
TI  - (18)F-FDG PET in localization of frontal lobe epilepsy: comparison of visual and
      SPM analysis.
AB  - The sensitivity of (18)F-FDG PET to localize epileptogenic zones in frontal lobe
      epilepsy was evaluated by both visual assessment and statistical parametric
      mapping (SPM). METHODS: Twenty-nine patients with frontal lobe epilepsy were
      examined. All patients showed good outcome after surgical resection (Engel class
      I or II). On pathologic examination, 22 patients had cortical dysplasia, 4 had
      tumors, 1 had cortical scars, and 2 had an old infarct. Hypometabolic lesions
      were found on (18)F-FDG PET images by both visual assessment and SPM analysis. On
      SPM analysis, the cutoff threshold was varied and sensitivity to find
      epileptogenic zones was compared. RESULTS: MRI showed structural lesions in 15
      patients and normal findings in 14. (18)F-FDG PET correctly localized the
      epileptogenic zones in 16 patients (55%) by visual assessment. The sensitivity of
      (18)F-FDG PET was 36% in patients without structural lesions on MRI and 73% in
      patients with structural lesions. On SPM analysis, using an uncorrected
      probability value of 0.005 as the threshold, the sensitivity of SPM analysis was
      66%, which was not statistically different from the sensitivity of visual
      assessment. The sensitivity decreased according to the decrease in probability
      value. CONCLUSION: (18)F-FDG PET was sensitive in localizing epileptogenic zones
      by revealing hypometabolic areas in nonlesional patients with frontal lobe
      epilepsy as well as in lesional patients. SPM analysis showed a comparable
      sensitivity to visual assessment and could be used as an aid in diagnosing
      epileptogenic zones in frontal lobe epilepsy.

PMID- 12215555
TI  - Limited sensitivity of parathyroid imaging with (99m)Tc-sestamibi/(123)I
      subtraction in an endemic goiter area.
AB  - Double-phase single-tracer scintigraphy with (99m)Tc-sestamibi is now generally
      used for parathyroid imaging but, at least in endemic goiter areas, complementary
      thyroid scintigraphy is recommended. Although (123)I-sodium iodide is considered
      to be the optimal thyroid agent, it is hardly ever used because of high costs and
      logistic difficulties. Our study presents the results of using the (99m)Tc
      sestamibi/(123)I subtraction technique in a region with a high goiter prevalence.
      Special attention was paid to the changes in sensitivity and specificity and
      their relationship to thyroid volume as well as to autonomous and nodular thyroid
      disease. METHODS: One hundred three scintigraphic parathyroid examinations on 96
      patients were included in this study. Fifty-eight of all patients had concomitant
      morphologic or functional alterations of the thyroid. Initially, 10 MBq (123)I
      sodium iodide were injected. Then, 150 MBq (99m)Tc-sestamibi were administered
      after 3-5 h, followed by planar scintigraphic imaging of the neck and upper chest
      region using a double-isotope technique. RESULTS: An area with increased tracer
      uptake on the subtraction image was found in 44 cases. Forty-three of them proved
      to be true-positive. No suspicious lesions were detected scintigraphically on the
      remaining 59 examinations. However, histologic examination revealed a parathyroid
      adenoma or hyperplasia in 11 of these cases. The mean parathyroid volume of these
      false-negative patients was 0.9 mL. Secondary hyperparathyroidism with multiple
      enlarged parathyroid glands was found in 4 of these cases. The sensitivity of the
      parathyroid scintigraphy was 80% (43/54) and the specificity was 98% (48/49).
      There was a distinct difference in the sensitivity between the subgroups with
      thyroid volumes of >15 mL and <15 mL (76% vs. 88%), although the resected
      parathyroid glands had a similar size in both subgroups. The specificity was 97%
      and 100%, respectively. No significant difference in the sensitivity and
      specificity was observed between the subgroups with and without morphologic or
      functional alterations of the thyroid (80% vs. 79% and 96% vs. 100%,
      respectively). CONCLUSION: The sensitivity of parathyroid imaging with (99m)Tc
      sestamibi/ (123)I subtraction depends mainly on the thyroid and parathyroid
      volumes rather than on the presence of nodular or autonomous thyroid disease.

PMID- 12215556
TI  - Improved body-outline imaging technique for localization of sentinel lymph nodes
      in breast surgery.
AB  - Many centers use techniques for localizing the sentinel lymph node (SLN)
      associated with a breast tumor. Protocols involve the use of an intraoperative
      probe and blue dye but may or may not include scintigraphy. METHODS: Three
      methods of body-outline imaging were investigated to aid SLN localization. Body
      outlines were acquired using a handheld source; a transmission image was acquired
      from a (57)Co-flood source; and, finally, a new method is described using a
      (153)Gd-line source attenuation correction for body outline. RESULTS: Method 1
      images were of low quality, although 83% of SLNs were visualized. Body outline
      was unsatisfactory for surgical localization. Method 2 was unsatisfactory because
      of the lack of a lateral image. Method 3 enabled good presurgical visualization
      of the SLN (73%) and speeded surgical localization. CONCLUSION: The (153)Gd-line
      source consistently gives optimal-quality body-outline images. This source is
      simple, quick, and clearly locates the SLN on multiple projections.

PMID- 12215557
TI  - Comparison of mutual information-based warping accuracy for fusing body CT and
      PET by 2 methods: CT mapped onto PET emission scan versus CT mapped onto PET
      transmission scan.
AB  - This article assesses the resulting accuracies of 2 registration methods using
      the same multimodal mutual information registration algorithm. In the indirect,
      fusion method, the CT dataset is warped onto the PET transmission scan, and then
      the patient's attenuation-corrected emission dataset is substituted for the
      transmission dataset. In the direct, fusion method, the CT is warped directly
      onto the attenuation-corrected emission dataset. METHODS: CT and (18)F-FDG PET
      image datasets from 14 subjects with malignant lesions in the thorax were
      registered. In both CT and PET imaging acquisitions, the patient's arms were at
      the patient's side, resting on the scanning couch in a manner similar to that of
      routine PET acquisition procedures. The accuracy of the 2 warping registrations
      was assessed by measuring the distance between lesion centroids on CT and PET
      emission after fusion. RESULTS: The indirect method has a statistically smaller
      mean error, 6.2 mm, than the direct method, 10.6 mm. CONCLUSION: The indirect
      method appears to be the more accurate/reliable choice for fusing body CT and FDG
      PET.

PMID- 12215558
TI  - Sodium iodide symporter: its role in nuclear medicine.
AB  - Thyroid iodide uptake is basic to the clinical applications of radioiodine.
      Iodide uptake occurs across the membrane of the thyroid follicular cells through
      an active transporter process mediated by the sodium iodide symporter (NIS). The
      recent cloning of the NIS gene enabled the better characterization of the
      molecular mechanisms underlying iodide transport, thus opening the way to the
      clarification and expansion of its role in nuclear medicine. In papillary and
      follicular carcinoma, NIS immunostaining was positive in only a few tumor cells,
      and no NIS protein expression was detected in anaplastic carcinomas. Decreased
      NIS expression levels account for the reduced iodide uptake in thyroid
      carcinomas. Thus, by targeting NIS expression in cancer cells, we could enable
      these cells to concentrate iodide from plasma and in so doing offer the
      possibility of radioiodine therapy. Several investigators have shown that gene
      transfer of NIS into a variety of cell types confers increased radioiodine uptake
      by up to several hundredfold that of controls in nonthyroid cancers as well as in
      thyroid cancer. In addition, my group proposes that NIS may serve as an
      alternative imaging reporter gene in addition to the HSVtk and dopaminergic
      receptor genes. The NIS has the potential to expand the role of nuclear medicine
      in the future, just as it has served as the base for the development of nuclear
      medicine in the past.

PMID- 12215559
TI  - Increased tumor uptake of 3-(123)I-Iodo-L-alpha-methyltyrosine after preloading
      with amino acids: an in vivo animal imaging study.
AB  - 3-(123)I-Iodo-L-alpha-methyltyrosine (3-IMT) is an amino acid analog used for
      tumor imaging. Specific accumulation is mediated mainly by the system L amino
      acid transport system. System L activity is known to increase when cells are
      loaded with amino acids. The aim of our study was to measure the effects of amino
      acid preload on (123)I-3-IMT tumor uptake and image contrast in a rat tumor model
      using in vivo dynamic imaging. METHODS: Rhabdomyosarcoma (R1M) tumor-bearing rats
      underwent 2 dynamic (123)I-3-IMT studies on separate days: 1 baseline study and 1
      after intraperitoneal injection (0.25 mmol/kg) of a single amino acid (arginine,
      proline, glutamate, asparagine, tryptophan, or phenylalanine) administered 30 min
      before intravenous injection of 18.5 MBq (123)I-3-IMT. A (99m)Tc-labeled human
      serum albumin study was performed on each rat for the calculation of the blood
      pool activity inside the tumor. Time-activity curves were generated for tumor,
      contralateral background region, kidney, heart, and total body. Tumor uptake was
      corrected for blood-pool and background activity. Image contrast was calculated
      as the ratio between tumor and background activity. The rate (K(1)) of tracer
      entering the tumor was obtained using Patlak analysis. A displacement study was
      performed on a separate group of rats, in which a high dose of phenylalanine was
      administered 40 min after (123)I-3-IMT injection. RESULTS: (123)I-3-IMT
      accumulation in tumor reached a plateau 10 min after injection. Tumor uptake on
      the baseline scans correlated well with tumor size (r = 0.92). After preloading,
      tumor uptake and contrast increased in all conditions: arginine, +26% and +26%;
      proline, +15% and +13%; glutamate, +14% and +9%; asparagine, +19% and +15%;
      tryptophan, +36% and 11%; phenylalanine, +22% and + 13%. K(1) values also
      increased. Administration of an afterload with phenylalanine induced a
      significant displacement of (123)I-3-IMT tumor accumulation. CONCLUSION: Prior
      amino acid administration increases (123)I-3-IMT tumor accumulation and image
      contrast. This effect can be explained by the increased antiporter activity of
      the amino acid transport system L in preloaded conditions. Our results indicate
      that the fasted state might not be the optimal metabolic condition to study tumor
      accumulation of L-transported tracers such as (123)I-3-IMT. Amino acid
      administration before (123)I-3-IMT injection could improve tumor uptake and image
      contrast.

PMID- 12215560
TI  - Improving amino acid imaging: hungry or stuffed?

PMID- 12215561
TI  - Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549
      carcinoma cells.
AB  - The thymidine analog (18)F-3'-deoxy-3' -fluorothymidine (FLT) is being used
      clinically for PET imaging of tumor proliferation. Appropriate use of this tracer
      requires validating the mechanisms by which it accumulates in dividing cells. We
      tested the accuracy with which FLT uptake predicted the activity of cytosolic
      thymidine kinase-1 (TK(1)), an enzyme that is upregulated before and during DNA
      synthesis. METHODS: Cultured A549 human lung carcinoma cells were manipulated to
      a range of proliferation rates from actively dividing to growth arrested. Uptake
      of radiolabeled FLT was compared with cell cycle activity, which was expressed as
      the percentage of cells in S phase, and with activity of cytosolic TK(1). We also
      compared uptake of FLT and deoxyglucose. We genetically manipulated A549 cells by
      transfecting them with human papillomavirus type 16 E6 (designated A549-E6) to
      abrogate function of the tumor suppressor gene, p53. Although radiation typically
      inhibits progression of mammalian cells through the cell cycle, abrogation of p53
      function eliminates this inhibition. We then compared FLT uptake with the
      percentage of cells in S phase and TK(1) activity in irradiated A549-E6 cells and
      in irradiated control cells having normal p53 function and the expected radiation
      induced growth delay. RESULTS: A549 cells with only 3%-5% cells in S phase took
      up little FLT and had low levels of TK(1) activity. When cells were stimulated to
      grow by being placed into fresh medium, we observed a strong correlation between
      increased FLT uptake and increased TK(1) activity. As expected, FLT uptake varied
      much more as a function of growth than did uptake of deoxyglucose.
      Nonproliferating A549 cells did not enter the cell cycle if they were irradiated
      before being placed into fresh medium, and they did not accumulate FLT or show
      elevated TK(1) activity. In contrast, radiation did not inhibit the cell cycle
      progression of A549-E6 cells. When subcultured, they began to grow and showed
      increased uptake of FLT commensurate with greater TK(1) activity. CONCLUSION: In
      cultured A549 cells FLT uptake is positively correlated with cell growth and
      TK(1) activity. Inhibition of cell cycle progression prevents FLT uptake and
      increased TK(1) activity. These results suggest that FLT images reflect TK(1)
      activity and the percentage of cells in S phase.

PMID- 12215562
TI  - Rationale of 5-(125)I-iodo-4'-thio-2'-deoxyuridine as a potential iodinated
      proliferation marker.
AB  - The aim of this investigation was to synthesize and test a novel metabolically
      stable iodinated nucleoside as a proliferation-imaging agent for SPECT. METHODS:
      5-Iodo-4'-thio-2'-deoxyuridine (ITdU) and 5-iodo-1-(4-thio-beta-D
      arabinofuranosyl)uracil (ITAU) were tested. The radiolabeling of ITdU and ITAU
      with (125)I was achieved by a destannylation reaction of the trimethylstannyl
      precursor of each nucleoside. The products were isolated in high yields and with
      >99% radiochemical purities. RESULTS: (125)I-ITdU was effectively phosphorylated
      by cytosolic nucleoside kinases and specifically incorporated into a thymidine
      kinase-expressing L-M cell rather than a thymidine kinase-deficient mutant L-M
      (TK(-)) cell. In addition, an in vitro cell metabolism study of (125)I-ITdU
      clarified that (125)I-ITdU was effectively and specifically incorporated into a
      DNA fraction (>90% at 60 min). Therefore, (125)I-ITdU was proven to be an ideal
      DNA synthesis marker such as 5-(125)I-iodo-2'-deoxyuridine (IUdR). In contrast,
      (125)I-ITAU was neither remarkably phosphorylated by cytosolic nucleoside kinases
      nor notably incorporated into an L-M cell rather than an L-M (TK(-)) cell. (125)I
      ITdU and (125)I-ITAU showed a higher resistance to phosphorolytic cleavage by
      recombinant thymidine phosphorylase than did (125)I-IUdR. Furthermore,
      biodistribution of (125)I-ITdU and (125)I-ITAU revealed better in vivo stability
      of radioiodination than that of (125)I-IUdR. (125)I-ITdU also displayed a
      significantly higher uptake in proliferating organs (thymus, spleen, small
      intestine, and bone) than in nonproliferating organs (brain, muscle, liver, and
      lung), as did (125)I-IUdR, at 18 h after injection. As indicated by the in vitro
      study, (125)I-ITAU did not show any significant uptake in proliferating organs.
      CONCLUSION: Radioiodine-labeled ITdU is potentially useful as a proliferation
      imaging agent, and further studies should clarify the usefulness of this compound
      as a tumor-imaging agent.

PMID- 12215563
TI  - In vivo quantification of myocardial dihydropyridine binding sites: a PET study
      in dogs.
AB  - Abnormalities in myocardial L-type Ca(2+) channel abundance and function have
      been described in cardiac hypertrophy and failure. In vivo quantification of the
      density of these channels using PET and an adequate ligand would provide new
      insights into cardiac disease. METHODS: The dihydropyridine L-type Ca(2+) channel
      antagonist S12968 (3-ethyl 5-methyl (-)-2-[(2-(2-aminoethoxy)ethoxy)methyl]-4
      (2,3-dichlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate) was labeled
      with (11)C and injected in various amounts (5-23 nmol), 20 or 30 min apart, into
      dogs. This protocol allowed a separate evaluation of the density of binding sites
      (B(max)) as well as association and dissociation rate constants. The parameters
      were calculated using a nonlinear mathematic model. RESULTS: Using the
      multiinjection approach, a complete model describing interactions between S12968
      and the dihydropyridine binding sites was obtained. B(max) was found to be 19.2
      +/- 3.3 pmol x mL(-1) of tissue. Association and dissociation constants
      (estimated by K(on)/VR and K(d)VR, respectively) were found to be 0.015 +/- 0.01
      mL x pmol(-1) x min(-1) and 4.2 +/- 2.2 nmol x mL(-1), respectively. CONCLUSION:
      The present data suggest that it is possible to measure myocardial
      dihydropyridine binding site density with a single radiosynthesis and a simple
      PET protocol that is not time consuming (75 min for the total examination,
      including transmission and emission scans). This methodology can be useful to
      investigate human cardiac disease in vivo.

PMID- 12215564
TI  - (123)I- or (125)I-metaiodobenzylguanidine visualization of brown adipose tissue.
AB  - (123)I-Metaiodobenzylguanidine (MIBG) accumulations that do not correspond to any
      tumor are observed occasionally on the medial aspect of the upper back or
      shoulder of children. The true nature of such accumulations is unknown, and we
      hypothesized that they represent interscapular brown adipose tissue (IBAT)
      visualized by scintigraphy. METHODS: Wistar rats (7 wk old) received MIBG labeled
      with (123)I or (125)I. Autoradiography was performed, and concentrations of the
      tracer in the interscapular subcutaneous tissue were identified
      histopathologically. The effects of 6-hydroxydopamine, reserpine, and beta 3
      adrenergic receptor agonist (CL316,243) on the accumulation were investigated to
      elucidate the mechanism of uptake into BAT. RESULTS: Autoradiography showed well
      defined distinct accumulation in the subcutaneous tissue on the upper back, and
      hematoxylin-eosin and anti-uncoupling protein 1 antibody staining confirmed that
      it was BAT. The percentage injected dose per gram in BAT was as high as that in
      the heart and was quite different from the concentration in white adipose tissue.
      Preadministration of 6-hydroxydopamine or reserpine resulted in lower MIBG
      concentrations in BAT. Activation of the beta 3-adrenergic receptor accelerated
      the washout of MIBG in BAT and caused an increase in concentration in white
      adipose tissue. CONCLUSION: MIBG accumulates in the adrenergic nervous system in
      BAT, and IBAT is distinguished from the surrounding white adipose tissue. To our
      knowledge, BAT has not been visualized previously. We showed that MIBG
      scintigraphy might be suitable for the investigation of BAT and treatment of
      human obesity.

PMID- 12215565
TI  - Calculating the absorbed dose from radioactive patients: the line-source versus
      point-source model.
AB  - In calculations of absorbed doses from radioactive patients, the activity
      distribution in such patients is generally assumed to be an unattenuated point
      source and the dose to exposed individuals at a given distance is therefore
      calculated using the inverse square law. In many nuclear medicine patients, the
      activity distribution is widely dispersed and does not simulate a point source.
      In these cases, a line-source model is proposed to more accurately reflect this
      extended activity distribution. METHODS: Calculations of dose rate per unit
      activity were performed for a point source and for line sources of lengths of 20,
      50, 70, 100, and 174 cm, and the ratios of line-source values to point-source
      values were calculated. In addition, radionuclide-independent conversion factors,
      to convert exposure rate constants to dose rates per unit activity, for these
      line-source lengths at various distances were determined. RESULTS: The calculated
      values, substantiated by published data, indicate that the inverse square law
      approximation is not valid for a line source until a certain distance is reached,
      dependent on the length of the line source. For the 20-, 50-, 70-, 100-, and 174
      cm line sources, the dose rate values estimated by the inverse square law
      approximation are within approximately 10% of the values estimated using the line
      source approach at distances of 20, 45, 60, 85, and 145 cm, respectively. At
      closer distances, use of the point-source model for a patient with an extended
      activity distribution will overestimate the radiation absorbed dose to exposed
      individuals, sometimes by a very significant amount. CONCLUSION: The line-source
      model is a more realistic and practical approach than the traditional point
      source model for determining the dose to individuals exposed to radioactive
      patients with widespread activity distributions.

PMID- 12215566
TI  - Improved prediction of myelotoxicity using a patient-specific imaging dose
      estimate for non-marrow-targeting (90)Y-antibody therapy.
AB  - For calculation of radiation dose to the marrow, standard dosimetry for
      radiopharmaceuticals that do not bind to the marrow includes dose contributions
      from radioactivity in blood and the remainder of the body. For a pure beta 
      emitter such as (90)Y, marrow dose is usually determined by the blood
      contribution. However, myelotoxicity from (90)Y-antibody therapy often correlates
      poorly with marrow dose estimated using the blood method. This study proposes a
      method to address 2 possible factors affecting marrow dose estimates. These
      include (a) recycled (90)Y in bone/marrow space after (90)Y-antibody has been
      processed in the liver and (b) use of the marrow mass of Reference Man for
      individual patients. METHODS: Thirty-three patients with advanced non-small cell
      lung cancer were treated with (90)Y-anti-TAG-72 murine antibody (CC49). TAG-72 is
      often expressed in epithelial-derived tumors but not in normal marrow. (111)In
      CC49 was used as a tracer. The marrow doses from blood were calculated on the
      basis of radioactivity concentrations in blood. Marrow dose in the lumbar
      vertebrae was estimated from images for (111)In-CC49 uptake in L2-L4. In 20
      patients who had CT images, trabecular bone volumes of L2-L4 were measured from
      CT images to estimate patient-specific marrow mass in L2-L4. The fraction of
      baseline platelet counts at nadir was used as an indicator of myelotoxicity.
      RESULTS: Marrow dose per unit injected radioactivity estimated from blood was
      lower than that from L2-L4 uptake values. Prediction of myelotoxicity using
      marrow dose estimated from blood was poorer than that using injected dose per
      body surface area (GBq/m(2)) (r = 0.31 vs. 0.51). Prediction was improved using
      marrow dose estimated from L2-L4 uptake, assuming the marrow mass of Reference
      Man (r = 0.67 for n = 33; r = 0.70 for n = 20). Prediction was worse if reference
      marrow mass was adjusted by body weight (r = 0.56 for n = 33; r = 0.63 for n =
      20). Prediction was not improved if adjusted by body surface area or lean body
      mass but was improved if adjusted by height (r = 0.72 for n = 33; r = 0.78 for n
      = 20). The best prediction was obtained (r = 0.85 for n = 20) using patient
      specific L2-L4 marrow mass estimated from CT. CONCLUSION: Marrow dose estimated
      from the blood radioactivity method was not a good predictor of myelotoxicity for
      non-marrow-targeting (90)Y-antibody therapy. Thrombocytopenia in this group of
      patients correlated much better with dose estimated from lumbar vertebrae imaging
      and patient-specific marrow mass than with that estimated from GBq/m(2) or
      standard marrow dose based on blood.

PMID- 12215567
TI  - Radioiodine therapy induces dose-dependent in vivo oxidation injury: evidence by
      increased isoprostane 8-epi-PGF(2 alpha).
AB  - 131I is the treatment of choice for differentiated thyroid cancer and
      hyperthyroidism. A relationship between low-density lipoprotein oxidation and
      radioiodine therapy-related side effects, consequently inducing increased
      formation of 8-epi-prostaglandin F(2 alpha) (PGF(2 alpha)) in situ, has recently
      been reported by several investigators. Isoprostanes, among them 8-epi-PGF(2
      alpha), have been associated with increased oxidation injury due to various
      pathologic conditions in vivo. The aim of this study was to investigate the
      possible induction of oxidative stress as a consequence of (131)I therapy.
      METHODS: 8-epi-PGF(2 alpha) was examined in plasma, serum, and urine in 42
      patients undergoing radioiodine treatment of hyperthyroidism or thyroid cancer.
      The 8-epi-PGF(2 alpha) levels were analyzed daily for 1 wk and thereafter at
      different points up to 12 wk after treatment. RESULTS: The isoprostane levels
      showed an increase after application of radioiodine in all investigated
      compartments. The effect was significantly higher and longer lasting after higher
      activity therapy (2,960 or 7,400 MBq) than after lower-activity therapy (185 or
      740 MBq). CONCLUSION: These findings document a significant, dose-dependent in
      vivo oxidation injury as a consequence of therapeutic radioiodine application to
      the salivary gland.

PMID- 12215568
TI  - Effect of mechanically simulated diaphragmatic respiratory motion on myocardial
      SPECT processed with and without attenuation correction.
AB  - The goal of this study was to assess the effect of diaphragmatic respiratory
      motion on inferior wall cold artifact in myocardial SPECT and to assess the
      ability of attenuation correction (AC) to correct for this artifact in the
      presence of diaphragmatic motion. METHODS: We used an anthropomorphic phantom
      with ventricular wall activity, variable ventricular caudal tilt, attenuating
      liver and spleen cold inserts, and variable vertical (diaphragmatic) motion
      amplitude and pattern. Cardiac SPECT images were acquired on a gamma camera with
      dual scanning transmission line sources and commercially available AC software
      (with scatter correction and iterative reconstruction). The acquired data were
      processed either using filtered backprojection or with the AC software. The
      resulting myocardial activity maps were processed with polar plots and with
      standardized inferior-to-anterior and anterior-to-lateral wall ratios. RESULTS:
      Subdiaphragmatic attenuation reduces inferior wall counts and this component of
      inferior wall artifact is fully corrected by AC relative to anterior wall counts
      both with and without diaphragmatic respiratory motion. In the phantom,
      diaphragmatic motion artifact manifests as reduction in relative count density in
      both the anterior wall and the inferior wall relative to the lateral wall, which
      is not corrected by AC. This artifact becomes more marked with increasing
      respiratory amplitude and its symmetry depends on the pattern of diaphragmatic
      motion. CONCLUSION: Images with AC acquired at small respiratory amplitudes
      (approximately 2 cm) in the phantom resemble images with AC found in published
      normal patient databases. These results support a clinical need for respiratory
      gating of myocardial SPECT images.

PMID- 12215569
TI  - Optimization of injected dose based on noise equivalent count rates for 2- and 3
      dimensional whole-body PET.
AB  - The noise equivalent count (NEC) rate index is used to derive guidelines on the
      optimal injected dose to the patient for 2-dimensional (2D) and 3-dimensional
      (3D) whole-body PET acquisitions. METHODS: We performed 2D and 3D whole-body
      acquisitions of an anthropomorphic phantom modeling the conditions for (18)F-FDG
      PET of the torso and measured the NEC rates for different activity levels for
      several organs of interest. The correlations between count rates measured from
      the phantom and those from a series of whole-body patient scans were then
      analyzed. This analysis allowed validation of our approach and estimation of the
      injected dose that maximizes NEC rate as a function of patient morphology for
      both acquisition modes. RESULTS: Variations of the phantom and patient prompt and
      random coincidence rates as a function of single-photon rates correlated well. On
      the basis of these correlations, we demonstrated that the patient NEC rate can be
      predicted for a given single-photon rate. Finally, we determined that patient
      single-photon rates correlated with the mean dose per weight at acquisition start
      when normalized by the body mass index. This correlation allows modifying the
      injected dose as a function of patient body mass index to reach the peak NEC rate
      in 3D mode. Conversely, we found that the peak NEC rates were never reached in 2D
      mode within an acceptable range of injected dose. CONCLUSION: The injected dose
      was adapted to patient morphology for 2D and 3D whole-body acquisitions using the
      NEC rate as a figure of merit of the statistical quality of the sinogram data.
      This study is a first step toward a more comprehensive comparison of the image
      quality obtained using both acquisition modes.

PMID- 12215570
TI  - Inflammation, cell adhesion molecules, and stroke: tools in pathophysiology and
      epidemiology?

PMID- 12215571
TI  - Is CT or MRI the method of choice for imaging patients with acute stroke? Why
      should men divide if fate has united?

PMID- 12215572
TI  - C-reactive protein in ischemic stroke.

PMID- 12215573
TI  - Alzheimer disease as a vascular disorder: nosological evidence.

PMID- 12215574
TI  - Recurrent cerebral venous thrombosis in a 24-year-old puerperal woman.

PMID- 12215575
TI  - Re: Clinical and imaging findings in cryptogenic stroke patients with and without
      patent foramen ovale.

PMID- 12215576
TI  - Evaluation of risk factors for stroke/embolism and of complications due to
      anticoagulant therapy in atrial fibrillation.

PMID- 12215577
TI  - Risk factors for aneurysmal subarachnoid hemorrhage.

PMID- 12215578
TI  - Global cerebral edema after subarachnoid hemorrhage.

PMID- 12215579
TI  - Body temperature in acute stroke.

PMID- 12215580
TI  - Induction of mucosal tolerance to E-selectin prevents ischemic and hemorrhagic
      stroke in spontaneously hypertensive genetically stroke-prone rats.
AB  - BACKGROUND AND PURPOSE: Inflammatory and immune mechanisms can precipitate
      cerebrovascular thrombosis and hemorrhage. Immunologic tolerance can be induced
      to a specific antigen by intranasal instillation of that antigen. Lymphocytes
      tolerized in this way provide local immunosuppression on restimulation with the
      same antigen. This study tests whether tolerization of lymphocytes to E-selectin
      can suppress local vessel activation and prevent stroke. METHODS: Spontaneously
      hypertensive genetically stroke-prone rats (n=113) were distributed among the
      following studies: comparison of ischemic infarcts/intraparenchymal hemorrhages
      after single or repetitive tolerization schedules with ovalbumin, E-selectin, or
      PBS; comparison of E-selectin tolerization- and PBS tolerization-induced
      suppression of delayed-type hypersensitivity in animals subsequently sensitized
      to E-selectin; and comparison of PBS-, ovalbumin-, and E-selectin-tolerized
      groups (after intravenous lipopolysaccharide to activate vessels) regarding
      transforming growth factor-beta1-positive splenocyte counts, plasma interferon
      gamma levels, anti-human E-selectin antibodies, endothelial intercellular
      adhesion molecule-1, and anti-endothelial cell antibodies. RESULTS: Nasal
      instillation of E-selectin, which is specifically expressed on activated
      endothelium, potently inhibited the development of ischemic and hemorrhagic
      strokes in spontaneously hypertensive stroke-prone rats with untreated
      hypertension. Repeated schedules of tolerization were required to maintain the
      resistance to stroke. Suppression of delayed-type hypersensitivity to E-selectin
      and increased numbers of transforming growth factor-beta1-positive splenocytes
      showed that intranasal exposure to E-selectin induced immunologic tolerance. E
      selectin tolerization also reduced endothelial activation and immune responses
      after intravenous lipopolysaccharide, as shown by marked suppression of
      intercellular adhesion molecule-1 expression, anti-endothelial cell antibodies on
      luminal endothelium, and plasma interferon-gamma levels compared with the control
      condition. CONCLUSIONS: The novel findings in this study support further
      investigation of immunologic tolerance as applied to the prevention of stroke.

PMID- 12215581
TI  - Air pollution: a new risk factor in ischemic stroke mortality.
AB  - BACKGROUND AND PURPOSE: Air pollution is known to be associated with
      cardiovascular disease, but little is known about the occurrence of stroke in
      relation to air pollution. We investigated the association between acute stroke
      mortality and air pollution over a 7-year period (January 1991 through December
      1997) in Seoul, Korea. METHODS: A generalized additive model was used to regress
      daily stroke death counts for each air pollutant, controlling for time trends,
      day of the week, and meteorological influences such as temperature, relative
      humidity, and atmospheric pressure. Ischemic and hemorrhagic stroke deaths were
      examined separately. RESULTS: The effects of air pollutants on ischemic stroke
      mortality were statistically significant, whereas this was not the case for
      hemorrhagic stroke mortality. We observed estimated relative risks of 1.03 (95%
      CI, 1.00 to 1.06) and 1.04 (95% CI, 1.01 to 1.08) for ischemic stroke mortality
      for each interquartile range increase in total suspended particulates and sulfur
      dioxide concentrations on the same day. We also found significantly increased
      relative risks of 1.04 (95% CI, 1.01 to 1.07) for nitrogen dioxide with a 1-day
      lag, of 1.06 (95% CI, 1.02 to 1.09) for carbon monoxide with a 1-day lag, and of
      1.06 (95% CI, 1.02 to 1.10) for ozone with a 3-day lag for each interquartile
      range increase. CONCLUSIONS: These findings indicate that air pollutants are
      significantly associated with ischemic stroke mortality, which suggests an acute
      pathogenetic process in the cerebrovascular system induced by air pollution.

PMID- 12215582
TI  - Active and passive smoking, chronic infections, and the risk of carotid
      atherosclerosis: prospective results from the Bruneck Study.
AB  - BACKGROUND AND PURPOSE: Susceptibility of the vasculature to the injurious
      effects of smoking varies substantially, with some smokers developing severe
      premature atherosclerosis and others remaining free of advanced atheroma until
      high ages. The present study sought to estimate the contribution of chronic
      infections to the variability of atherosclerosis severity among smokers. METHODS:
      In the community-based Bruneck Study, 5-year changes in carotid atherosclerosis
      were assessed by high-resolution ultrasound. Early atherogenesis was defined by
      the development of nonstenotic plaques and advanced atherogenesis by the
      development/progression of vessel stenosis >40%. RESULTS: The risk of early
      atherogenesis strongly relied on lifetime smoking exposure and remained elevated
      long-term after cessation of smoking. Remarkably, current and ex-smokers faced an
      increased atherosclerosis risk only in the presence of chronic infections (odds
      ratios [95% CIs], 3.3 [1.8 to 6.2] and 3.4 [1.8 to 6.3]; P<0.001 each), whereas
      current, past, and nonsmokers without infections did not differ substantially in
      their estimated risk burden (odds ratios [95% CIs], 1.4 [0.8 to 2.4], 0.9 [0.6 to
      1.6], and 1.0 [reference group]). In analogy to first-hand smoking, subjects
      exposed to environmental tobacco smoke were found to be vulnerable to the
      manifestation of chronic infection, and only those infected experienced a high
      atherosclerosis risk. The risk of advanced atherogenesis showed a dose-response
      relation with the number of daily cigarettes, returned to normal shortly after
      cessation of smoking, and emerged as independent of infectious illness.
      CONCLUSIONS: Our study provides the first epidemiological evidence that the
      proatherogenic effects of cigarette smoking are mediated in part by the chronic
      infections found in smokers. A better understanding of the vascular pathogenetic
      mechanisms of smoking may offer novel clues for disease prevention supplementary
      to the primary goal of achieving long-term abstinence.

PMID- 12215583
TI  - Plasma homocysteine levels and atherosclerosis in Japan: epidemiological study by
      use of carotid ultrasonography.
AB  - BACKGROUND AND PURPOSE: We examined whether hyperhomocysteinemia is an
      independent risk factor for increased carotid artery intimal-medial wall
      thickness (IMT) in a large, randomly selected community in Japan where the
      dietary habit is different and the incidence of coronary artery disease is lower
      compared with those of western countries. METHODS: In 1111 cases (452 men, 659
      women) aged 63+/-10 years old (range, 40 to 94 years) recruited from a population
      based survey performed in 1999, we measured fasting plasma total homocysteine
      levels and performed bilateral carotid B-mode ultrasound. The participants
      underwent measurements of other blood chemistries (total cholesterol, HDL
      cholesterol, glycosylated hemoglobin A(1c), and creatinine). RESULTS: For the
      total population, the mean total homocysteine level was 10.9 micro mol/L. Total
      homocysteine levels were higher in men than in women and increased with aging.
      With multiple linear regression analysis after adjustments for age and sex, the
      most powerful determinant of total homocysteine levels was serum creatinine
      (P<0.001). With multiple stepwise regression analysis after adjustments for age,
      sex, and other confounding factors, total homocysteine was significantly (P<0.05)
      related to IMT. Furthermore, when mean values of IMT adjusted for age, sex, and
      other related factors were analyzed across total homocysteine quartiles, IMT
      (P<0.05) showed a significant trend as total homocysteine level increased.
      CONCLUSIONS: Plasma total homocysteine levels in Japan are similar to those
      reported in western countries. Mild hyperhomocysteinemia is an independent risk
      factor for increased carotid artery wall thickness in Japan as well.

PMID- 12215584
TI  - Soluble intercellular adhesion molecule-1 and risk of future ischemic stroke: a
      nested case-control study from the Bezafibrate Infarction Prevention (BIP) study
      cohort.
AB  - BACKGROUND AND PURPOSE: Inflammation is considered to be involved in the
      pathogenesis of ischemic stroke. Our purpose was to assess the role of soluble
      intercellular adhesion molecule-1 (sICAM-1) concentration, a marker of
      inflammation, in predicting future ischemic stroke among patients at risk because
      of chronic coronary heart disease. METHODS: We obtained baseline serum samples
      from patients with chronic coronary heart disease enrolled in the Bezafibrate
      Infarction Prevention trial (n=3090), which assessed the efficacy of bezafibrate
      in secondary prevention. Using a prospective nested case-control design, we
      measured baseline sICAM-1 concentration in sera of patients who developed
      ischemic stroke during a mean follow-up of 8.2 years (cases, n=134) and in age-
      and sex-matched controls without any subsequent cardiovascular events (n=134).
      RESULTS: Baseline serum concentrations of sICAM-1 were significantly higher in
      cases compared with controls (379 versus 350 ng/mL, P<0.05). sICAM-1
      concentration at the highest quartile (>394 ng/mL) was associated with
      significantly higher relative odds of ischemic stroke compared with the lower
      concentrations after adjustment for potential confounding variables (relative
      odds, 2.1; 95% CI, 1.1 to 4.3). After fibrinogen and total white blood cell count
      were added to the multivariable model, the relative odds were 2.1 (95% CI, 1.1 to
      4.2) and 2.2 (95% CI, 1.1 to 4.8), respectively. The risk associated with raised
      concentrations of sICAM-1 seemed to be highest for large disabling strokes of
      cardioembolic origin. CONCLUSIONS: Elevated concentrations of sICAM-1, a marker
      of inflammation, are associated with increased risk of ischemic stroke,
      independent of other traditional cerebrovascular risk factors and of plasma
      fibrinogen, among patients at increased risk because of manifest coronary heart
      disease.

PMID- 12215585
TI  - Is the hypercoagulable state in atrial fibrillation mediated by vascular
      endothelial growth factor?
AB  - BACKGROUND AND PURPOSE: Tissue factor (TF; an initiator of coagulation) and
      vascular endothelial growth factor (VEGF; a marker of angiogenesis) are involved
      in the hypercoagulable state associated with malignancy. We investigated their
      roles in chronic atrial fibrillation (AF), a condition also associated with
      increased risk of stroke and thromboembolism, as well as a prothrombotic or
      hypercoagulable state. METHODS: We studied 25 patients with AF (20 men; mean+/-SD
      age, 62+/-13 years) who were compared with 2 control groups in sinus rhythm: 30
      healthy control subjects (17 men; mean age, 60+/-9 years) and 35 patient control
      subjects with coronary artery disease (CAD; 27 men; mean age, 60+/-12 years).
      Plasma levels of TF, VEGF, and the VEGF receptor sFlt-1 were measured by enzyme
      linked immunosorbent assay. RESULTS: VEGF, sFlt-1, and TF were significantly
      different between the 3 groups, with abnormal levels in AF and CAD patients
      compared with control subjects (P<0.001, P=0.022, and P=0.008, respectively).
      Among the AF patients, TF levels were significantly correlated with VEGF
      (Spearman's r=0.65, P<0.001) and sFlt (r=0.54, P=0.006) levels. Only TF and VEGF
      levels were significantly correlated in CAD patients (r=0.39, P=0.02). There were
      no significant correlations among the healthy control subjects. CONCLUSIONS:
      Patients with chronic AF have high TF levels, in keeping with the prothrombotic
      state associated with this arrhythmia. The relationships between TF and VEGF and
      its receptor sFlt-1 in AF suggest a possible role for VEGF in the hypercoagulable
      state found in AF, as seen in malignancy and atherosclerosis.

PMID- 12215586
TI  - Ultrastructural connective tissue aberrations in patients with intracranial
      aneurysms.
AB  - BACKGROUND AND PURPOSE: An unknown connective tissue defect might predispose for
      the development and rupture of intracranial aneurysms in some patients. This
      study of connective tissue samples of a series of patients with intracranial
      aneurysms investigates the morphology of the extracellular matrix with methods
      that are currently used in the routine diagnosis of inherited connective tissue
      disorders. METHODS: Skin biopsies from 21 patients with intracranial aneurysms,
      many with multiple aneurysms, were studied by electron microscopy. None of the
      patients included in this study showed clinical signs of a known connective
      tissue disorder. RESULTS: In 7 patients (33%), we observed repetitive aberrations
      in the morphology of collagen fibrils and elastic fibers of the reticular dermis.
      The observed ultrastructural findings were somewhat similar to those typically
      observed in patients with Ehlers-Danlos syndrome (EDS) and in a subgroup of
      patients with spontaneous cervical artery dissections. The patterns of
      abnormalities fell into 2 classes: 4 patients displayed abnormalities that
      resembled those found in patients with EDS type III, and the electron microscopic
      findings in the skin biopsies from 3 patients resembled those of EDS type IV
      patients. The sequence of the COL3A1 gene from the patients with EDS type IV-like
      alterations of the connective tissue morphology was analyzed. No mutation was
      detected. CONCLUSIONS: Connective tissue alterations were found in skin biopsies
      from a minority of patients with intracranial aneurysms. Electron microscopic
      investigation of skin biopsies from patients and their relatives might become
      valuable for clinical diagnostics, identification of persons at risk, and basic
      studies of the pathogenesis of this vascular disease.

PMID- 12215587
TI  - Prediction of early neurological deterioration using diffusion- and perfusion
      weighted imaging in hyperacute middle cerebral artery ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Early neurological deterioration (END) occurs in
      approximately one third of all ischemic stroke patients and is associated with a
      poor outcome. Our study sought to assess the value of ultra-early MRI in the
      prediction of END in stroke patients. METHODS: Between August 1999 and November
      2001, 38 stroke patients with a proven middle cerebral artery (MCA) or
      intracranial internal carotid artery (ICA) occlusion on MR angiography underwent
      perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) within 6
      hours after onset, and 30 fulfilled all inclusion criteria. Control DWI and MR
      angiography were performed between days 3 and 5. Cranial CT was performed to rule
      out hemorrhagic transformation. Vascular risk factors, temperature, blood
      pressure, glycemia, and blood count were assessed on admission. National
      Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and at
      6, 12, 24, and 48 hours. At the same time points, transcranial Doppler (TCD)
      examinations were conducted to assess arterial recanalization. END was defined as
      an increase in the NIHSS score >4. A logistic regression model was applied to
      detect independent predictors of END. The Kruskal-Wallis test was used to
      evaluate the relationship between infarct growth and duration of vessel
      occlusion. RESULTS: Initial MR angiography showed an occlusion of intracranial
      ICA in 7 patients (23.3%), of proximal MCA in 14 (46.6%), and of distal MCA in
      the remaining 9 (30%). A PWI-DWI mismatch >20% was observed in 28 patients
      (93.3%). END occurred in 7 patients (23.3%). Baseline NIHSS score (P=0.05),
      proximal site of occlusion (P=0.002), initial DWI (P=0.002) and PWI (P=0.003)
      volumes, and reduced PWI-DWI mismatch (P=0.038) were associated with END in the
      univariate analysis. Only hyperacute DWI volume remained as a predictor of END
      when a logistic regression model was applied (odds ratio, 11.5; 95% CI, 2.31 to
      57.10; P=0.0028). A receiver operator characteristic curve identified a cutoff
      point of DWI >89 cm(3) (sensitivity, 85.7%; specificity, 95.7%) to predict END. A
      graded response was seen in DWI lesion expansion in relation to duration of
      arterial occlusion (P=0.017). CONCLUSIONS: Ultra-early DWI is a powerful
      predictor of END after MCA or intracranial ICA occlusion.

PMID- 12215588
TI  - CT and diffusion-weighted MR imaging in randomized order: diffusion-weighted
      imaging results in higher accuracy and lower interrater variability in the
      diagnosis of hyperacute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Diffusion-weighted MRI (DWI) has become a commonly used
      imaging modality in stroke centers. The value of this method as a routine
      procedure is still being discussed. In previous studies, CT was always performed
      before DWI. Therefore, infarct progression could be a reason for the better
      result in DWI. METHODS: All hyperacute (<6 hours) stroke patients admitted to our
      emergency department with a National Institutes of Health Stroke Scale (NIHSS)
      score >3 were prospectively randomized for the order in which CT and MRI were
      performed. Five stroke experts and 4 residents blinded to clinical data judged
      stroke signs and lesion size on the images. To determine the interrater
      variability, we calculated kappa values for both rating groups. RESULTS: A total
      of 50 patients with ischemic stroke and 4 patients with transient symptoms of
      acute stroke (median NIHSS score, 11; range, 3 to 27) were analyzed. Of the 50
      patients, 55% were examined with DWI first. The mean delay from symptom onset
      until CT was 180 minutes; that from symptom onset until DWI was 189 minutes. The
      mean delay between DWI and CT was 30 minutes. The sensitivity of infarct
      detection by the experts was significantly better when based on DWI (CT/DWI,
      61/91%). Accuracy was 91% when based on DWI (CT, 61%). Interrater variability of
      lesion detection was also significantly better for DWI (CT/DWI, kappa=0.51/0.84).
      The assessment of lesion extent was less homogeneous on CT (CT/DWI,
      kappa=0.38/0.62). The differences between the 2 modalities were stronger in the
      residents' ratings (CT/DWI: sensitivity, 46/81%; kappa=0.38/0.76). CONCLUSIONS:
      CT and DWI performed with the same delay after onset of ischemic stroke resulted
      in significant differences in diagnostic accuracy. DWI gives good interrater
      homogeneity and has a substantially better sensitivity and accuracy than CT even
      if the raters have limited experience.

PMID- 12215589
TI  - Optimizing the technique of contrast transcranial Doppler ultrasound in the
      detection of right-to-left shunts.
AB  - BACKGROUND AND PURPOSE: A cardiac right-to-left shunt (RLS) can be identified by
      transesophageal echocardiography and transcranial Doppler ultrasound (TCD) with
      contrast agents and a Valsalva maneuver (VM) as a provocation procedure. This
      article applies the modalities of these tests detailed in previous studies to a
      large patient cohort and compares 2 contrast agents (saline and Echovist-300).
      METHODS: Eighty-one patients were investigated by both transesophageal
      echocardiography and bilateral TCD of the middle cerebral arteries. The following
      protocol with injections of 10 mL agitated saline was applied in a randomized
      way: (1) no VM, (2) VM for 5 seconds starting 5 seconds after the beginning of
      contrast injection, and (3) repetition of the test with VM if the first test with
      VM was negative. The VM was performed for 5 seconds starting exactly 5 seconds
      after the beginning of saline injection. Thereafter, the same protocol was
      repeated with 10 mL Echovist-300 instead of saline. RESULTS: Thirty-one patients
      had a cardiac RLS. The Echovist-300 investigation disclosed all these 31 shunts,
      but saline disclosed only 29 of them. Twenty-two had an RLS only in at least 1 of
      the above TCD tests, some of them even with a considerable shunt volume.
      CONCLUSIONS: Contrast TCD performed with Echovist-300 but not with saline yields
      a 100% sensitivity to identify transesophageal echocardiography-proven cardiac
      RLSs. The TCD test should be repeated if negative the first time. This article
      gives detailed information for the optimization of the contrast TCD technique.
      Extracardiac shunts detected only during contrast TCD can have a considerable
      shunt volume and may allow for paradoxical embolism.

PMID- 12215590
TI  - Detection of misery perfusion with split-dose 123I-iodoamphetamine single-photon
      emission computed tomography in patients with carotid occlusive diseases.
AB  - BACKGROUND AND PURPOSE: Patients with carotid occlusive disease and stage 2
      cerebral hemodynamic failure, characterized by an increased oxygen extraction
      fraction (OEF) as measured by positron emission tomography (PET) and otherwise
      known as misery perfusion, have a high risk of cerebral ischemia and subsequent
      stroke. In clinical practice, the detection of patients with misery perfusion
      through the use of widely available, noninvasive, and cost-effective modalities
      such as single-photon emission computed tomography (SPECT) is extremely
      important. METHODS: We evaluated the relationships between the regional
      hemodynamic status of cerebral circulation, measured with split-dose [123I] N
      isopropyl-p-iodoamphetamine SPECT (123I-IMP SPECT) and an acetazolamide
      challenge, and hemodynamic parameters, including OEF measured with PET, in 27
      patients with both unilateral and bilateral carotid occlusive diseases. RESULTS:
      A significant negative correlation was found between the SPECT-measured
      cerebrovascular reserve after acetazolamide administration and both the PET
      measured OEF and cerebral blood volume. Neither the cerebrovascular reserve nor
      the cerebral blood flow index, when expressed as a SPECT-measured cerebrum-to
      cerebellum ratio, was useful for detecting lesions with an elevated OEF. However,
      a combination of the cerebrovascular reserve and cerebral blood flow index showed
      high sensitivity, specificity, and positive predictive value for the detection of
      misery perfusion. CONCLUSIONS: Our study suggests that split-dose 123I-IMP SPECT
      with an acetazolamide challenge could be useful for screening patients with
      misery perfusion in carotid occlusive diseases.

PMID- 12215591
TI  - Mesencephalic and associated posterior circulation infarcts.
AB  - BACKGROUND AND PURPOSE: The purposes of this study were to evaluate and review
      the risk factors and clinical features of patients with posterior circulation
      stroke involving mesencephalon and neighboring structures and to describe the
      clinical syndromes according to the mesencephalic arterial territory involved.
      METHODS: We studied all patients with acute posterior circulation stroke
      involving mesencephalon who were admitted consecutively to our stroke unit over a
      6-year period. We selected these patients (3%) from 1296 patients with posterior
      circulation infarct. Neurological and radiological investigations, including MRI
      and angiography, were performed in all cases. We classified patients into 4
      groups on the basis of MRI findings: (1) isolated mesencephalic infarcts (9
      patients); (2) distal territory infarcts (19 patients), including mesencephalon,
      thalamus, medial temporal and occipital lobes, and cerebellum; (3) middle
      territory infarcts (12 patients), including the pons and anterior inferior
      cerebellar artery territory; and (4) proximal territory infarcts (1 patient),
      including the medulla and posterior inferior cerebellar artery territory.
      RESULTS: Middle mesencephalon involvement was the most common in all groups, and
      the anteromedial territory was frequently affected, depending on the direct
      perforators of basilar artery. In patients with isolated mesencephalic infarct,
      the clinical picture was dominated by nuclear or fascicular third-nerve palsy and
      contralateral motor deficits. The distal territory involvement was the most
      common and associated with consciousness disturbances, gait ataxia, ocular motor
      disturbances, and visual field deficits. The neurological picture of middle
      territory infarcts was dominated by consciousness disturbances with dysarthria,
      horizontal ocular motor disorders, and hemiparesis. Proximal territory
      involvement was rare and associated with acute unsteadiness, vertigo, dysphagia,
      dysphonia, tetra-ataxia, and motor weakness. The most common cause of stroke was
      large-artery disease in 16 patients (39%), cardioembolism in 8 (20%), and small
      artery disease with lacunar mesencephalic infarct in 10 (24%). Bilateral
      mesencephalic infarcts were not uncommon (27%), mainly in patients with multiple
      and extended infarcts in the posterior circulation, and were associated with poor
      outcome compared with unilateral infarct. CONCLUSIONS: Our study highlights the
      topographic and clinical heterogeneity of the acute posterior circulation
      infarcts involving mesencephalon. The variety of the underlying potential causes
      of stroke requires detailed investigations of the extra and intracranial arteries
      and the heart.

PMID- 12215592
TI  - Treatment of basilar artery embolism with a mechanical extraction device:
      necessity of flow reversal.
AB  - BACKGROUND AND PURPOSE: The success of local fibrinolysis in vertebrobasilar
      thromboembolism depends on the volume and composition of the clot. Since
      thrombolysis can also be time consuming and cause bleeding, we investigated the
      feasibility of a mechanical clot retraction device based on a nitinol basket
      advanced through a microcatheter. METHODS: Five patients with acute embolism of
      the basilar artery who presented with progressive stroke and impaired
      consciousness were included in a multicenter study (Neuronet Evaluation in
      Embolic Stroke Disease [NEED]). In 3 patients flow reversal was induced with the
      use of silicone balloons or coaxial catheters. Three patients required additional
      fibrinolysis. RESULTS: The device failed to retrieve the clots in our first 2
      patients with distal basilar artery embolism. After successful recanalization by
      local fibrinolysis, both patients survived, 1 disabled and 1 with little residual
      impairment. In the next 3 patients the anterograde flow in the basilar artery was
      reversed during the short retraction period by temporarily blocking the vertebral
      or subclavian arteries. Two of these patients were completely recanalized by
      solely mechanical means; the third patient needed additional fibrinolysis before
      also being recanalized. All 3 patients survived: 1 remained disabled, 1 had
      almost a full recovery, and 1 became asymptomatic the day after the procedure.
      CONCLUSIONS: Mechanical thrombus extraction seems to be a feasible method for
      preventing infarction by rapid, complete, and safe recanalization of the basilar
      artery. We recommend the use of flow control to support retrieval of the thrombus
      (which the proximal flow would otherwise keep in place like a cork) and to
      protect the distal vessels from embolization by fragments.

PMID- 12215593
TI  - Baseline blood pressure but not early computed tomography changes predicts major
      hemorrhage after streptokinase in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage is the most serious complication
      of thrombolytic therapy for stroke. We explored factors associated with this
      complication in the Australian Streptokinase Trial. METHODS: The initial CT scans
      (< or =4 hours after stroke) of 270 patients were reviewed retrospectively by an
      expert panel for early signs of ischemia and classified into the following 3
      categories: no signs or < or =1/3 or >1/3 of the vascular territory. Hemorrhage
      on late CT scans was categorized as major or minor on the basis of location and
      mass effect. Stepwise, backward elimination, multivariate logistic regression
      analysis was used to identify risk factors for each hemorrhage category. RESULTS:
      Major hemorrhage occurred in 21% of streptokinase (SK) and 4% of placebo
      patients. Predictors of major hemorrhage were SK treatment (odds ratio [OR],
      6.40; 95% CI, 2.50 to 16.36) and elevated systolic blood pressure before therapy
      (OR, 1.03; 95% CI, 1.01 to 1.05). Baseline systolic blood pressure >165 mm Hg in
      SK-treated patients resulted in a >25% risk of major secondary hemorrhage. Early
      ischemic CT changes, either < or =1/3 or >1/3, were not associated with major
      hemorrhage (OR, 1.58; 95% CI, 0.65 to 3.83; and OR, 1.11; 95% CI, 0.45 to 2.76,
      respectively). Minor hemorrhage occurred in 30% of the SK and 26% of the placebo
      group. Predictors of minor hemorrhage were male sex, severe stroke, early CT
      changes, and SK treatment. Ninety-one percent of patients with major hemorrhage
      deteriorated clinically compared with 23% with minor hemorrhage. CONCLUSIONS: SK
      increased the risk of both minor and major hemorrhage. Major hemorrhage was also
      more likely in patients with elevated baseline systolic blood pressure. However,
      early CT changes did not predict major hemorrhage. Results from this study
      highlight the importance of baseline systolic blood pressure as a potential cause
      of hemorrhage in patients undergoing thrombolysis.

PMID- 12215594
TI  - Improving the assessment of outcomes in stroke: use of a structured interview to
      assign grades on the modified Rankin Scale.
AB  - BACKGROUND AND PURPOSE: The modified Rankin Scale is widely used to assess
      changes in activity and lifestyle after stroke, but it has been criticized for
      its subjectivity. The purpose of the present study was to compare conventional
      assessment on the modified Rankin Scale with assessment through a structured
      interview. METHODS: Sixty-three patients with stroke 6 to 24 months previously
      were interviewed and graded independently on the modified Rankin Scale by 2
      observers. These observers then underwent training in use of a structured
      interview for the scale that covered 5 areas of everyday function. Eight weeks
      after the first assessment, the same observers reassessed 58 of these patients
      using the structured interview. RESULTS: Interrater reliability was measured with
      the kappa statistic (weighted with quadratic weights). For the scale applied
      conventionally, overall agreement between the 2 raters was 57% (kappa(w)=0.78); 1
      rater assigned significantly lower grades than the other (P=0.048). On the
      structured interview, the overall agreement between raters was 78%
      (kappa(w)=0.93), and there was no overall difference between raters in grades
      assigned (P=0.17). Rankin grades from the conventional assessment and the
      structured interview were highly correlated, but there was significantly less
      disagreement between raters when the structured interview was used (P=0.004).
      CONCLUSIONS: Variability and bias between raters in assigning patients to Rankin
      grades may be reduced by use of a structured interview. Use of a structured
      interview for the scale could potentially improve the quality of results from
      clinical studies in stroke.

PMID- 12215595
TI  - Perception of verticality after recent cerebral hemispheric stroke.
AB  - BACKGROUND AND PURPOSE: Perception of the subjective visual vertical (SVV) is
      affected by cerebral hemispheric lesions. Knowledge of this disturbance is of
      interest for the study of its possible relation to balance disturbances. There is
      still uncertainty about the possible effects of a visual field defect and of the
      side and site of the lesion. This study was conducted to assess SVV with the head
      upright or tilted and to explore its relation to a visual field defect,
      visuospatial neglect, and the site of lesion. METHODS: Forty patients with
      hemiplegia after a recent hemispheric stroke (20 with left and 20 with right
      stroke) were studied. The site of the lesion was determined on CT scan, with
      special attention focused on the vestibular cortex. A neurological examination
      with determination of the visual field and visual neglect was conducted before
      SVV was tested. Subjects sat in a dark room and adjusted a luminous rod to the
      vertical position. Measures were repeated with binocular and monocular vision and
      with the head upright or tilted to the right or left. RESULTS: SVV was abnormally
      deviated in 23 of 40 patients (57%). The deviation was significantly greater
      among patients with a right or left hemispheric lesion than among healthy
      controls (-2.2 degrees and 1.5 degrees versus 0.2 degrees ); the same applied to
      the range of uncertainty (7.6 degrees and 4.7 degrees versus 1.9 degrees ). SVV
      deviation was not significantly related to the location of the lesion but was
      closely related to visuospatial neglect. The "E" effect observed in controls with
      the head tilted, ie, an SVV shift in the direction opposite to the head tilt, was
      not observed in hemiplegic patients with the head tilted toward the nonparetic
      side. CONCLUSIONS: Recent hemispheric stroke affects SVV perception, which is
      closely correlated to visuospatial neglect. It is suggested that the E effect
      might be mediated by the stretching of the somatosensory structure of the neck.

PMID- 12215596
TI  - Incidence of dementia after ischemic stroke: results of a longitudinal study.
AB  - BACKGROUND AND PURPOSE: A number of cross-sectional epidemiological studies have
      reported that one fourth of elderly patients meet criteria for dementia 3 months
      after ischemic stroke, but few longitudinal studies of the incidence of dementia
      after stroke have been performed. We conducted the present study to investigate
      the incidence and clinical predictors of dementia after ischemic stroke. METHODS:
      We administered neurological, neuropsychological, and functional assessments
      annually to 334 ischemic stroke patients (age, 70.4+/-7.5 years) and 241 stroke
      free control subjects (age, 70.6+/-6.5 years), all of whom were nondemented in
      baseline examinations. We diagnosed incident dementia using modified Diagnostic
      and Statistical Manual of Mental Disorders, Revised Third Edition criteria
      requiring deficits in memory and > or =2 additional cognitive domains, as well as
      functional impairment. RESULTS: The crude incidence rate of dementia was 8.49
      cases per 100 person-years in the stroke cohort and 1.37 cases per 100 person
      years in the control cohort. A Cox proportional-hazards analysis found that the
      relative risk (RR) of incident dementia associated with stroke was 3.83 (95% CI,
      2.14 to 6.84), adjusting for demographic variables and baseline Mini-Mental State
      Examination score. Within the stroke cohort, intercurrent medical illnesses
      associated with cerebral hypoxia or ischemia were independently related to
      incident dementia (RR, 4.40; 95% CI, 2.20 to 8.85), adjusting for recurrent
      stroke, demographic variables, and baseline Mini-Mental State Examination score.
      CONCLUSIONS: The risk of incident dementia is high among patients with ischemic
      stroke, particularly in association with intercurrent medical illnesses that
      might cause cerebral hypoxia or ischemia, suggesting that cerebral hypoperfusion
      may serve as a basis for some cases of dementia after stroke.

PMID- 12215597
TI  - Cessation of smoking after first-ever stroke: a follow-up study.
AB  - BACKGROUND AND PURPOSE: Cessation of smoking is widely recommended in patients
      with stroke to reduce the risk of myocardial infarction and recurrent stroke, but
      little is known regarding how patients modify their smoking habits after a
      stroke. We used data from a prospective follow-up study to assess modification of
      smoking habits and to identify predictors of persistent smoking after first-ever
      stroke. METHODS: All patients admitted to the only neurology department of Funen
      County (465 000 inhabitants) with first-ever stroke from August 1, 1999, to
      January 31, 2001, were prospectively identified. A comprehensive structured
      interview was completed both during hospitalization and at 6-month follow-up. The
      interview comprised questions on education, occupation, marital status,
      lifestyle, concomitant diseases, and functional disability. We estimated the
      relative risk of persistent smoking at follow-up using unconditional logistic
      regression. RESULTS: We identified 734 patients with a first-ever stroke in the
      study period. One hundred three patients (14%) died in the 6-month period after
      their admission. A total of 511 patients (81%) who participated in the interview
      both on admission and at follow-up were included in the present study. Among 198
      patients (38.7%) who were current smokers on admission, 43 patients (21.7%) gave
      up smoking within 6 months of suffering a stroke. Sex, functional status, and
      sociodemographic characteristics were independently associated with persistent
      smoking. CONCLUSIONS: Our results suggest that more efficient antismoking
      counseling is required to reduce the proportion of persistent smokers after
      stroke. This counseling should take into account the increased risk of persistent
      smoking in men, patients with no disability, blue-collar workers, and patients
      living alone.

PMID- 12215598
TI  - Effects of implantation site of stem cell grafts on behavioral recovery from
      stroke damage.
AB  - BACKGROUND AND PURPOSE: Findings that MHP36 stem cells grafted into intact
      parenchyma contralateral to the lesion induced by middle cerebral artery
      occlusion promoted recovery from stroke deficits led us to investigate whether
      implantation site of stem cells affects the functional efficacy of MHP36 grafts.
      METHODS: MHP36 cells (200 000/8 microL) were implanted in the left (n=8) or right
      (n=9) parenchyma or infused into the right ventricle (intraventricular; n=7) 2 to
      3 weeks after stroke induced by 60 minutes of intraluminal right middle cerebral
      artery occlusion. Additionally, intact (n=11) and stroke (n=7) control groups
      were tested for 14 weeks in bilateral asymmetry, rotation bias, and spatial
      learning tasks before histological investigation of cell distribution and
      differentiation. RESULTS: Rats with left and right parenchymal grafts showed
      reduced bilateral asymmetry but no improvement in spatial learning. Conversely,
      spatial learning improved in rats with intraventricular grafts, but marked
      asymmetry persisted. No grafted group showed reduced amphetamine-induced rotation
      bias or reduced lesion volume relative to stroke controls. In all grafted groups,
      cells occupied both sides of the brain. A third of cells grafted in the striatum
      crossed the midline to occupy homologous regions in intact and lesioned
      hemispheres and differentiated into site-appropriate phenotypes. CONCLUSIONS:
      After stroke, both the intact and lesioned hemispheres attract grafted stem
      cells, suggesting repair processes that utilize cells both for local repair and
      to augment plastic changes in contralateral motor pathways. However, differential
      effects of parenchymal and intraventricular grafts suggest that different
      mechanisms are implicated in recovery from cognitive and sensorimotor deficits
      induced by stroke.

PMID- 12215599
TI  - Microplasmin: a novel thrombolytic that improves behavioral outcome after embolic
      strokes in rabbits.
AB  - BACKGROUND AND PURPOSE: It has been proposed that the novel thrombolytic
      microplasmin may be useful in the treatment of ischemic stroke. In the present
      study the effects and safety profile of microplasmin were evaluated in 2 rabbit
      embolic stroke models that have been used successfully to develop tissue
      plasminogen activator (tPA) as the only Food and Drug Administration-approved
      treatment for stroke. The rabbit small clot embolic stroke model (RSCEM) and
      rabbit large clot embolic stroke model (RLCEM) were used to determine the
      potential neuroprotective properties and safety profile of microplasmin,
      respectively, after an embolic stroke. METHODS: Rabbits were embolized by
      injecting small blood clots (RSCEM) or large blood clots (RLCEM) into the
      cerebral circulation. For the RSCEM, 126 rabbits were included, with behavioral
      analysis conducted 24 hours later, allowing for determination of the effective
      stroke dose (ES50) or clot amount (milligrams) that produces severe neurological
      deficits in 50% of rabbits. For RLCEM safety study analysis, 47 rabbits were
      included, with postmortem analyses consisting of assessment of hemorrhage and
      infarct rate and size. In test animals microplasmin was infused intravenously 60
      minutes after embolization, whereas control rabbits were given infusions of the
      saline/Plasma-Lyte vehicle with all assessments performed in a blinded fashion.
      RESULTS: In the RSCEM, a drug is considered neuroprotective if it significantly
      increases the ES50 compared with the vehicle-treated control group. The ES50 of
      the vehicle-treated control group 24 hours after embolization was 1.36+/-0.42 mg
      (n=38). Microplasmin, infused starting 60 minutes after embolization, increased
      the ES50 to 2.32+/-0.57 (n=21), 1.89+/-0.48 (n=21), 2.81+/-0.55 (n=22), and
      1.89+/-0.28 mg (n=24) for the 1-, 2-, 4-, and 8-mg/kg doses, respectively. There
      was a statistically significant behavioral improvement in the 4-mg/kg dose arm
      (P=0.040). The microplasmin dose of microplasmin that was statistically
      significant (4 mg/kg) was subsequently determined to be safe in the RLCEM because
      it did not increase the incidence of hemorrhages (56%) compared with vehicle
      treated rabbits (63%), nor did it significantly alter hemorrhage volume, infarct
      rate, or infarct volume. CONCLUSIONS: The present study shows that microplasmin
      improves behavioral rating scores in the RSCEM when administered 60 minutes after
      embolization, at a dose that does not increase hemorrhages in the RLCEM. This is
      in contrast to tPA, which significantly enhances the hemorrhage rate in the
      RLCEM.

PMID- 12215600
TI  - Altered endothelial Ca2+ regulation after ischemia/reperfusion produces
      potentiated endothelium-derived hyperpolarizing factor-mediated dilations.
AB  - BACKGROUND AND PURPOSE: Endothelium-derived hyperpolarizing factor (EDHF)
      mediated dilations are potentiated after several pathologies, including
      ischemia/reperfusion (I/R). However, no study to date has addressed the mechanism
      by which this potentiation occurs. This study tested the hypothesis that
      potentiated EDHF-mediated dilations are due to altered endothelial Ca2+ handling
      after I/R. METHODS: Rat middle cerebral arteries (MCAs) were isolated after 2
      hours of MCA occlusion and 24 hours of reperfusion (or sham surgery). This model
      has been previously demonstrated to produce potentiated EDHF-mediated dilations.
      MCAs were studied in a pressurized/perfused vessel chamber equipped for the
      simultaneous measurement of endothelial Ca2+ (with fura 2) and artery diameter.
      Measures were made after luminal administration of UTP (P2Y2 purinoceptor
      agonist), 2 MeS-ATP (P2Y1 purinoceptor agonist), and Br-A23187 (receptor
      independent Ca2+ ionophore) for sham and I/R MCAs. RESULTS: I/R resulted in
      significantly potentiated UTP-mediated dilations (through a P2Y2 purinoceptor)
      and endothelial Ca2+ responses in the presence of N(G)-nitro-L-arginine methyl
      ester (L-NAME) and indomethacin. Endothelial Ca2+ and diameter responses were
      also significantly potentiated with 2 MeS-ATP (through a P2Y1 purinoceptor) when
      L-NAME and indomethacin were absent. Br-A23187, a receptor-independent Ca2+
      ionophore, produced significantly potentiated endothelial Ca2+ responses after
      I/R in the presence of L-NAME/indomethacin. Evaluation of artery diameter as a
      function of endothelial Ca2+ demonstrated no differences between sham and I/R
      groups. CONCLUSIONS: These findings demonstrate that I/R results in augmented
      endothelial Ca2+ responses that appear to be downstream of the receptor level.
      Moreover, these data suggest that this augmented Ca2+ response contributes to the
      potentiated EDHF-mediated dilations after I/R.

PMID- 12215601
TI  - Gene transfer of inducible nitric oxide synthase impairs relaxation in human and
      rabbit cerebral arteries.
AB  - BACKGROUND AND PURPOSE: These studies evaluated whether gene transfer of
      inducible nitric oxide synthase (iNOS) is a sufficient stimulus to produce
      vascular dysfunction in cerebral arteries. METHODS: Intracranial (pial) arteries
      were dissected from human brain tissue obtained during elective surgery. Isolated
      human arteries were incubated in vitro with adenovirus containing iNOS (AdiNOS)
      or a nonexpressive transgene (control, AdBglII) (500 micro L, 3x10(9) plaque
      forming units per milliliter), and vascular function was examined 24 hours later.
      In anesthetized rabbits, AdiNOS or AdBglII (300 microL 1x10(10)) was injected
      into the cisterna magna. Three days later, the basilar artery was removed, and
      reactivity was examined ex vivo. RESULTS: In submaximally precontracted vessels,
      we observed impairment of NO-dependent relaxation in human cerebral arteries
      after gene transfer of iNOS. Maximum relaxation to bradykinin (1 micromol/L, an
      endothelium-dependent agonist) was 77+/-11% (mean+/-SE) after AdBglII and 31+/
      22% (P<0.05) after AdiNOS. After AdiNOS, responses to nitroprusside (an
      endothelium-independent NO donor) also were impaired. Responses to both
      nitroprusside and bradykinin were improved by aminoguanidine (300 micromol/L), an
      inhibitor of iNOS. AdiNOS produced no change in vasoconstrictor responses to
      U46619. In basilar arteries from rabbits examined in vitro after gene transfer in
      vivo, responses to histamine, serotonin, and nitroprusside all were similar after
      AdiNOS or AdBglII. In contrast, relaxation to acetylcholine was significantly
      depressed after AdiNOS. Maximum relaxation to acetylcholine (10 micromol/L) was
      90+/-3% after AdBglII and 68+/-5% (P<0.05) after AdiNOS. Relaxation of arteries
      after AdiNOS was improved by aminoguanidine. CONCLUSIONS: These studies suggest
      that expression of iNOS may impair NO-dependent relaxation in both human and
      rabbit cerebral arteries.

PMID- 12215602
TI  - Protection against ischemia and improvement of cerebral blood flow in genetically
      hypertensive rats by chronic pretreatment with an angiotensin II AT1 antagonist.
AB  - BACKGROUND AND PURPOSE: Pretreatment with angiotensin II AT(1) receptor
      antagonists protects against cerebral ischemia. We studied whether modulation of
      cerebral blood flow (CBF) and morphometric changes in brain arteries participated
      in this protective mechanism. METHODS: We pretreated adult spontaneously
      hypertensive rats with equally antihypertensive doses of candesartan (0.1 or 0.3
      mg/kg per day), nicardipine (0.1 mg/kg per day), or captopril (3.0 mg/kg per day)
      for 3 or 28 days via subcutaneous osmotic minipumps followed by permanent left
      middle cerebral artery (MCA) occlusion distal to the origin of the
      lenticulostriate arteries. We measured CBF by autoradiography with 4-iodo-[N
      methyl-(14)C]antipyrine 3 hours after operation and the areas of infarct and
      tissue swelling 24 hours after operation. Morphometric changes in the MCA were
      studied after antihypertensive treatment. RESULTS: Twenty-eight days of
      candesartan pretreatment decreased the infarct area by 31%; reduced the CBF
      decrease at the peripheral area of ischemia and the cortical volume of severe
      ischemic lesion, where CBF was <0.50 mL/g per minute; increased the MCA external
      diameter by 16%; and reduced the media thickness of the MCA by 23%. Captopril
      pretreatment for 28 days decreased the infarct area by 25%. Pretreatment with
      candesartan for 3 days or nicardipine for 28 days was ineffective. CONCLUSIONS:
      Angiotensin II system inhibition protects against neuronal injury more
      effectively than calcium channel blockade. Protection after AT(1) receptor
      blockade is not directly correlated with blood pressure reduction but with
      normalization of MCA media thickness, leading to increased arterial compliance
      and reduced CBF decrease during ischemia at the periphery of the lesion.

PMID- 12215603
TI  - Neuroprotection by selective nitric oxide synthase inhibition at 24 hours after
      perinatal hypoxia-ischemia.
AB  - BACKGROUND AND PURPOSE: Perinatal hypoxia-ischemia is a major cause of neonatal
      morbidity and mortality. Until now no established neuroprotective intervention
      after perinatal hypoxia-ischemia has been available. The delay in cell death
      after perinatal hypoxia-ischemia creates possibilities for therapeutic
      intervention after the initial insult. Excessive nitric oxide and reactive oxygen
      species generated on hypoxia-ischemia and reperfusion play a key role in the
      neurotoxic cascade. The present study examines the neuroprotective properties of
      neuronal and inducible but not endothelial nitric oxide synthase inhibition by 2
      iminobiotin in a piglet model of perinatal hypoxia-ischemia. METHODS: Twenty
      three newborn piglets were subjected to 60 minutes of hypoxia-ischemia, followed
      by 24 hours of reperfusion and reoxygenation. Five additional piglets served as
      sham-operated controls. On reperfusion, piglets were randomly treated with either
      vehicle (n=12) or 2-iminobiotin (n=11). At 24 hours after hypoxia-ischemia, the
      cerebral energy state, presence of vasogenic edema, amount of apparently normal
      neuronal cells, caspase-3 activity, amount of terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL)-positive
      cells, and degree of tyrosine nitration were assessed. RESULTS: A 90% improvement
      in cerebral energy state, 90% reduction in vasogenic edema, and 60% to 80%
      reduction in apoptosis-related neuronal cell death were demonstrated in 2
      iminobiotin-treated piglets at 24 hours after hypoxia- ischemia. A significant
      reduction in tyrosine nitration in the cerebral cortex was observed in 2
      iminobiotin-treated piglets, indicating decreased formation of reactive nitrogen
      species. CONCLUSIONS: Simultaneous and selective inhibition of neuronal and
      inducible nitric oxide synthase by 2-iminobiotin is a promising strategy for
      neuroprotection after perinatal hypoxia-ischemia.

PMID- 12215604
TI  - Cerebral ischemia upregulates vascular endothelin ET(B) receptors in rat.
AB  - BACKGROUND AND PURPOSE: Elevated levels of endothelin-1 (ET-1) have been reported
      in cerebral ischemia. A role for ET may prove more important if the vascular
      receptors were changed. We addressed whether there is any change in ET receptor
      expression in cerebral ischemia. METHODS: The right middle cerebral artery (MCA)
      was occluded in male Wistar rats for 2 hours with the intraluminal filament
      method. The basilar artery and both MCAs were removed after 46 hours of
      recirculation. The contractile responses to ET-1, a combined ET(A) and ET(B)
      receptor agonist, and sarafotoxin 6c (S6c), a selective ET(B) receptor agonist,
      were examined in vitro, and ET receptor mRNA was quantified by real-time
      polymerase chain reaction. RESULTS: S6c, which had no contractile effect per se
      on fresh or sham-operated rat cerebral arteries, induced a marked contraction in
      the occluded MCA (E(max) [maximum contraction, calculated as percentage of the
      contractile capacity of 63.5 mmol/L K+]=68+/-68%; P<0.0001), while there was no
      difference in the responses to ET-1 after cerebral ischemia. Real-time polymerase
      chain reaction revealed a significant upregulation of both the ET(A) and ET(B)
      receptors (both P<0.05) in the occluded MCA compared with the nonoccluded MCA
      from the same rats. CONCLUSIONS: Focal cerebral ischemia in rat induces increased
      transcription of both ET(A) and ET(B) receptors, which results in the appearance
      of a contractile response to the ET(B) receptor agonist S6c. These results
      suggest a role for ET receptors in the pathogenesis of a vascular component after
      cerebral ischemia.

PMID- 12215605
TI  - Attenuation of cerebral vasospasm after subarachnoid hemorrhage in mice
      overexpressing extracellular superoxide dismutase.
AB  - BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) increases production of
      vascular extracellular superoxide anion (*O2-). We examined whether
      overexpression of murine extracellular superoxide dismutase (EC-SOD) alters SAH
      induced cerebral vasospasm, oxidative stress, and neurological outcome. METHODS:
      Mice exhibiting a 2-fold increase in vascular EC-SOD and wild-type (WT)
      littermates were subjected to sham surgery or SAH by perforation of the right
      anterior cerebral artery. Neurological deficits were scored 72 hours later.
      Middle cerebral artery (MCA) diameter was measured or immunohistochemically
      stained for nitrotyrosine. RESULTS: MCA diameter (mean+/-SD) was greater in EC
      SOD versus WT mice after SAH but not sham surgery (EC-SOD SAH=56+/-10 microm; WT
      SAH=38+/-13 microm [P<0.01]; EC-SOD sham=99+/-16 microm; WT sham=100+/-15
      microm). SAH decreased median (range) neurological score (scoring scale, 9 to 39;
      no deficit=39) versus shams, but there was no difference between EC-SOD and WT
      groups (EC-SOD SAH=26 [23 to 30]; WT SAH=23 [19 to 29] [P=0.27]; EC-SOD sham=39
      [39]; WT sham=39 [39]). Sensory-motor deficits correlated with MCA diameter
      (P<0.001) but worsened primarily between 60 and 50 micro m, plateauing below this
      threshold. The percentage of mice with MCA nitrotyrosine staining increased after
      SAH in WT (sham=29%; SAH=100% [P<0.05]) but not EC-SOD (sham=33%; SAH=44%
      [P=0.80]) mice. CONCLUSIONS: Endogenous overexpression of EC-SOD attenuated
      vasospasm and oxidative stress but failed to reduce neurological deficits after
      SAH. Extracellular *O2- likely plays a direct role in the etiology of vasospasm.

PMID- 12215606
TI  - Hypoxic depolarization of cerebellar granule neurons by specific inhibition of
      TASK-1.
AB  - BACKGROUND AND PURPOSE: The mechanisms underlying neuronal excitotoxicity during
      hypoxic/ischemic episodes are not fully understood. One feature of such insults
      is a rapid and transient depolarization of central neurons. TASK-1, an open
      rectifying K+ leak channel, is significant in setting the resting membrane
      potential of rat cerebellar granule neurons by mediating a standing outward K+
      current. In this study we investigate the theory that the transient neuronal
      depolarization seen during hypoxia is due to the inhibition of TASK-1. METHODS:
      Activity of TASK-1 in primary cultures of rat cerebellar granule neurons was
      investigated by the whole-cell patch-clamp technique. Discriminating
      pharmacological and electrophysiological maneuvers were used to isolate the
      specific channel types underlying acute hypoxic depolarizations. RESULTS:
      Exposure of cells to acute hypoxia resulted in a reversible and highly
      reproducible mean membrane depolarization of 14.2+/-2.6 mV (n=5; P<0.01). Two
      recognized means of inhibiting TASK-1 (decreasing extracellular pH to 6.4 or
      exposure to the TASK-1-selective inhibitor anandamide) abolished both the hypoxic
      depolarization and the hypoxic depression of a standing outward current,
      identifying TASK-1 as the channel mediating this effect. CONCLUSIONS: Our data
      provide compelling evidence that hypoxia depolarizes central neurons by specific
      inhibition of TASK-1. Since this hypoxic depolarization may be an early,
      contributory factor in the response of central neurons to hypoxic/ischemic
      episodes, TASK-1 may provide a potential therapeutic target in the treatment of
      stroke.

PMID- 12215607
TI  - New method of embolus preparation for standardized embolic stroke in rabbits.
AB  - BACKGROUND AND PURPOSE: Although thromboembolic stroke is caused by red, white,
      or mixed clots, the emboli previously used in animal studies on thrombolysis were
      more often red than white. Because this might be one of the reasons why
      thrombolysis is less effective in patients than in experimental stroke, we
      developed a new method of preparing highly standardized red and fibrin-rich white
      emboli. METHODS: The middle cerebral artery of 20 rabbits was embolized with
      either red or fibrin-rich white autologous emboli. Cerebral perfusion was
      monitored by MRI. RESULTS: Red emboli consisted of closely packed erythrocytes
      within a sparse fibrin net and white emboli of a dense mass of fibrin with only
      few other blood cells. Infarct volumes were 26+/-4% (mean+/-SD) of the ischemic
      hemisphere with red and 27+/-6% with white emboli. The relative regional cerebral
      blood volume dropped below 50% 90 minutes after vascular occlusion with either
      type of embolus. Late spontaneous lysis and hemorrhagic complications occurred in
      37.5% of red but not in white embolus cases. CONCLUSIONS: Emboli prepared by our
      technique result in standardized cerebral infarctions. Size and composition of
      the emboli continuously can be adjusted according to the experimental
      requirements.

PMID- 12215608
TI  - Intracerebral hemorrhage triggers interleukin-6 and interleukin-10 release in
      blood.
AB  - BACKGROUND AND PURPOSE: Acute brain insult can cause systemic anti-inflammatory
      response, including anti-inflammatory cytokine release. The goal of this study
      was to determine the serum level of interleukin-6, interleukin-10, and
      interleukin-13 in patients with intracerebral hemorrhage and to correlate
      cytokine concentrations with stroke severity. METHODS: Thirty patients with
      intraparenchymal hemorrhage and 16 control subjects were included. Serum samples
      were collected on the second day of hemorrhagic stroke. Cytokine level was
      measured with the enzyme-linked immunosorbent assay method. RESULTS: Increased
      serum levels of interleukin-6 and interleukin-10 were detected in stroke
      patients. Interleukin-6 and interleukin-10 levels were significantly correlated
      with Glasgow Coma Scale score. In addition, interleukin-6 level correlated with
      blood volume and mass effect. CONCLUSIONS: Intracerebral hemorrhage is associated
      with systemic release of anti-inflammatory cytokines.

PMID- 12215609
TI  - Gangliosides for acute ischemic stroke.

PMID- 12215610
TI  - ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins.

PMID- 12215611
TI  - Questions regarding nuclear emissions in cavitation experiments.

PMID- 12215612
TI  - Strengthening research in Europe.

PMID- 12215613
TI  - U.S. research funding. Physical sciences need boost, advisory panel tells Bush.

PMID- 12215614
TI  - Oceanography. Survey confirms coral reefs are in peril.

PMID- 12215615
TI  - Ozone depletion. A brighter outlook for good ozone.

PMID- 12215616
TI  - Plant sciences. Rescue planned for seed banks.

PMID- 12215617
TI  - Plant evolution. Elaborate carnivorous plants prove to be kin.

PMID- 12215618
TI  - Inflammatory arthritis. How immune system gangs up on joints.

PMID- 12215619
TI  - Science budgets. Japan's ministries no longer call the shots.

PMID- 12215620
TI  - Embryology. Embryo development at the click of a mouse.

PMID- 12215621
TI  - Confronting terrorism. One year after: tighter security reshapes research.

PMID- 12215622
TI  - Confronting terrorism. One year after: hunt for NIH funds fosters collaboration.

PMID- 12215623
TI  - Confronting terrorism. Profile: Janet Shoemaker, shaping the politics of
      bioterrorism.

PMID- 12215624
TI  - Undergraduate education. New lure for young talent: extreme research.

PMID- 12215625
TI  - ESA and Society for Ecological Restoration meeting. An ecological oasis in the
      desert.

PMID- 12215626
TI  - Plant tissue culture and biotechnology meeting. Getting down to bare wood and
      overcoming a barrier.

PMID- 12215627
TI  - Genome research. NSF's ark draws alligators, algae, and wasps.

PMID- 12215628
TI  - Profile: Dan Durda. Cave diving on asteroids.

PMID- 12215629
TI  - Portraits of science. Quick and magical shaper of science.

PMID- 12215630
TI  - Neuroscience. Single-neuron arithmetic.

PMID- 12215631
TI  - Chemical synthesis. Raising the bar for the "perfect reaction".

PMID- 12215633
TI  - Quantum mechanics. Putting a spin on the Aharonov-Bohm oscillations.

PMID- 12215632
TI  - Structure. Nitrogenase reveals its inner secrets.

PMID- 12215634
TI  - Applied physics. A dawn for carbon electronics?

PMID- 12215635
TI  - Geochemistry. The solar system's first clocks.

PMID- 12215636
TI  - New directions in neuronal migration.
AB  - Over the past decade, genetic analyses have yielded a more molecular view of
      neuronal migration and its role in central nervous system development. We now
      realize that many of the molecular mechanisms that guide migrations in
      invertebrates are recapitulated in the vertebrate nervous system. These
      mechanisms guide dorsoventral and anterior-posterior migrations and merge with
      radial migratory pathways that are prominent in the development of the mammalian
      cortex. This review discusses the choreography of these different migratory
      mechanisms within the context of genetic approaches that have defined their
      molecular mechanisms.

PMID- 12215637
TI  - A "greener" synthetic route for fluoroaromatics via copper (II) fluoride.

PMID- 12215638
TI  - High carrier mobility in single-crystal plasma-deposited diamond.
AB  - Room-temperature drift mobilities of 4500 square centimeters per volt second for
      electrons and 3800 square centimeters per volt second for holes have been
      measured in high-purity single-crystal diamond grown using a chemical vapor
      deposition process. The low-field drift mobility values were determined by using
      the time-of-flight technique on thick, intrinsic, freestanding diamond plates and
      were verified by current-voltage measurements on p-i junction diodes. The
      improvement of the electronic properties of single-crystal diamond and the
      reproducibility of those properties are encouraging for research on, and
      development of, high-performance diamond electronics.

PMID- 12215639
TI  - Iron emission lines from extended x-ray jets in SS 433: reheating of atomic
      nuclei.
AB  - Powerful relativistic jets are among the most ubiquitous and energetic
      observational consequences of accretion around supermassive black holes in active
      galactic nuclei and neutron stars and stellar-mass black holes in x-ray binary
      (XRB) systems. But despite more than three decades of study, the structure and
      composition of these jets remain unknown. Here we present spatially resolved x
      ray spectroscopy of arc second-scale x-ray jets from XRB SS 433 analyzed with the
      Chandra advanced charge-coupled device imaging spectrometer. These observations
      reveal evidence for a hot continuum and Doppler-shifted iron emission lines from
      spatially resolved regions. Apparently, in situ reheating of the baryonic
      component of the jets takes place in a flow that moves with relativistic bulk
      velocity even more than 100 days after launch from the binary core.

PMID- 12215640
TI  - Internal olefins to linear amines.
AB  - The selective synthesis of linear amines from internal olefins or olefin mixtures
      was achieved through a catalytic one-pot reaction consisting of an initial olefin
      isomerization followed by hydroformylation and reductive amination. Key to the
      success is the use of specially designed phosphine ligands in the presence of
      rhodium catalysts. This reaction constitutes an economically attractive and
      environmentally favorable synthesis of linear aliphatic amines.

PMID- 12215641
TI  - Lead isotopic ages of chondrules and calcium-aluminum-rich inclusions.
AB  - The lead-lead isochron age of chondrules in the CR chondrite Acfer 059 is 4564.7
      +/- 0.6 million years ago (Ma), whereas the lead isotopic age of calcium-aluminum
      rich inclusions (CAIs) in the CV chondrite Efremovka is 4567.2 +/- 0.6 Ma. This
      gives an interval of 2.5 +/- 1.2 million years (My) between formation of the CV
      CAIs and the CR chondrules and indicates that CAI- and chondrule-forming events
      lasted for at least 1.3 My. This time interval is consistent with a 2- to 3-My
      age difference between CR CAIs and chondrules inferred from the differences in
      their initial 26Al/27Al ratios and supports the chronological significance of the
      26Al-26Mg systematics.

PMID- 12215642
TI  - Diamond genesis, seismic structure, and evolution of the Kaapvaal-Zimbabwe
      craton.
AB  - The lithospheric mantle beneath the Kaapvaal-Zimbabwe craton of southern Africa
      shows variations in seismic P-wave velocity at depths within the diamond
      stability field that correlate with differences in the composition of diamonds
      and their syngenetic inclusions. Middle Archean mantle depletion events initiated
      craton keel formation and early harzburgitic diamond formation. Late Archean
      accretionary events involving an oceanic lithosphere component stabilized the
      craton and contributed a younger Archean generation of eclogitic diamonds.
      Subsequent Proterozoic tectonic and magmatic events altered the composition of
      the continental lithosphere and added new lherzolitic and eclogitic diamonds to
      the Archean diamond suite.

PMID- 12215643
TI  - Identification of a DNA nonhomologous end-joining complex in bacteria.
AB  - In eukaryotic cells, double-strand breaks (DSBs) in DNA are generally repaired by
      the pathway of homologous recombination or by DNA nonhomologous end joining
      (NHEJ). Both pathways have been highly conserved throughout eukaryotic evolution,
      but no equivalent NHEJ system has been identified in prokaryotes. The NHEJ
      pathway requires a DNA end-binding component called Ku. We have identified
      bacterial Ku homologs and show that these proteins retain the biochemical
      characteristics of the eukaryotic Ku heterodimer. Furthermore, we show that
      bacterial Ku specifically recruits DNA ligase to DNA ends and stimulates DNA
      ligation. Loss of these proteins leads to hypersensitivity to ionizing radiation
      in Bacillus subtilis. These data provide evidence that many bacteria possess a
      DNA DSB repair apparatus that shares many features with the NHEJ system of
      eukarya and suggest that this DNA repair pathway arose before the prokaryotic and
      eukaryotic lineages diverged.

PMID- 12215644
TI  - Mast cells: a cellular link between autoantibodies and inflammatory arthritis.
AB  - Previous studies have revealed that autoantibodies, complement components, and Fc
      receptors each participate in the pathogenesis of erosive arthritis in K/BxN
      mice. However, it is not known which cellular populations are responsive to these
      inflammatory signals. We find that two strains of mice deficient in mast cells,
      W/Wv and Sl/Sld, were resistant to development of joint inflammation and that
      susceptibility was restored in the W/Wv strain by mast cell engraftment. Thus,
      mast cells may function as a cellular link between autoantibodies, soluble
      mediators, and other effector populations in inflammatory arthritis.

PMID- 12215645
TI  - Nitrogenase MoFe-protein at 1.16 A resolution: a central ligand in the FeMo
      cofactor.
AB  - A high-resolution crystallographic analysis of the nitrogenase MoFe-protein
      reveals a previously unrecognized ligand coordinated to six iron atoms in the
      center of the catalytically essential FeMo-cofactor. The electron density for
      this ligand is masked in structures with resolutions lower than 1.55 angstroms,
      owing to Fourier series termination ripples from the surrounding iron and sulfur
      atoms in the cofactor. The central atom completes an approximate tetrahedral
      coordination for the six iron atoms, instead of the trigonal coordination
      proposed on the basis of lower resolution structures. The crystallographic
      refinement at 1.16 angstrom resolution is consistent with this newly detected
      component being a light element, most plausibly nitrogen. The presence of a
      nitrogen atom in the cofactor would have important implications for the mechanism
      of dinitrogen reduction by nitrogenase.

PMID- 12215646
TI  - Cooperation of GGAs and AP-1 in packaging MPRs at the trans-Golgi network.
AB  - The Golgi-localized, gamma-ear-containing, adenosine diphosphate ribosylation
      factor-binding proteins (GGAs) are multidomain proteins that bind mannose 6
      phosphate receptors (MPRs) in the Golgi and have an essential role in lysosomal
      enzyme sorting. Here the GGAs and the coat protein adaptor protein-1 (AP-1) were
      shown to colocalize in clathrin-coated buds of the trans-Golgi networks of mouse
      L cells and human HeLa cells. Binding studies revealed a direct interaction
      between the hinge domains of the GGAs and the gamma-ear domain of AP-1. Further,
      AP-1 contained bound casein kinase-2 that phosphorylated GGA1 and GGA3, thereby
      causing autoinhibition. This could induce the directed transfer of the MPRs from
      GGAs to AP-1. MPRs that are defective in binding to GGAs are poorly incorporated
      into AP-1-containing clathrin-coated vesicles. Thus, the GGAs and AP-1 interact
      to package MPRs into AP-1-containing coated vesicles.

PMID- 12215647
TI  - Inhibition of retroviral RNA production by ZAP, a CCCH-type zinc finger protein.
AB  - Cells have evolved multiple mechanisms to inhibit viral replication. To identify
      previously unknown antiviral activities, we screened mammalian complementary DNA
      (cDNA) libraries for genes that prevent infection by a genetically marked
      retrovirus. Virus-resistant cells were selected from pools of transduced clones,
      and an active antiviral cDNA was recovered. The gene encodes a CCCH-type zinc
      finger protein designated ZAP. Expression of the gene caused a profound and
      specific loss of viral messenger RNAs (mRNAs) from the cytoplasm without
      affecting the levels of nuclear mRNAs. The finding suggests the existence of a
      previously unknown machinery for the inhibition of virus replication, targeting a
      step in viral gene expression.

PMID- 12215648
TI  - Spatiotemporal pattern of neural processing in the human auditory cortex.
AB  - The principles that the auditory cortex uses to decipher a stream of acoustic
      information have remained elusive. Neural responses in the animal auditory cortex
      can be broadly classified into transient and sustained activity. We examined the
      existence of similar principles in the human brain. Sound-evoked, blood oxygen
      level-dependent signal response was decomposed temporally into independent
      transient and sustained constituents, which predominated in different portions
      core and belt-of the auditory cortex. Converging with unit recordings, our data
      suggest that this spatiotemporal pattern in the auditory cortex may represent a
      fundamental principle of analyzing sound information.

PMID- 12215649
TI  - Representation of the quantity of visual items in the primate prefrontal cortex.
AB  - Deriving the quantity of items is an abstract form of categorization. To explore
      it, monkeys were trained to judge whether successive visual displays contained
      the same quantity of items. Many neurons in the lateral prefrontal cortex were
      tuned for quantity irrespective of the exact physical appearance of the displays.
      Their tuning curves formed overlapping filters, which may explain why behavioral
      discrimination improves with increasing numerical distance and why discrimination
      of two quantities with equal numerical distance worsens as their numerical size
      increases. A mechanism that extracts the quantity of visual field items could
      contribute to general numerical ability.

PMID- 12215650
TI  - Little evidence for developmental plasticity of adult hematopoietic stem cells.
AB  - To rigorously test the in vivo cell fate specificity of bone marrow (BM)
      hematopoietic stem cells (HSCs), we generated chimeric animals by transplantation
      of a single green fluorescent protein (GFP)-marked HSC into lethally irradiated
      nontransgenic recipients. Single HSCs robustly reconstituted peripheral blood
      leukocytes in these animals, but did not contribute appreciably to
      nonhematopoietic tissues, including brain, kidney, gut, liver, and muscle.
      Similarly, in GFP+:GFP- parabiotic mice, we found substantial chimerism of
      hematopoietic but not nonhematopoietic cells. These data indicate that
      "transdifferentiation" of circulating HSCs and/or their progeny is an extremely
      rare event, if it occurs at all.

PMID- 12215651
TI  - Nanometer resolution and coherent optical dipole coupling of two individual
      molecules.
AB  - By performing cryogenic laser spectroscopy under a scanning probe electrode that
      induces a local electric field, we have resolved two individual fluorescent
      molecules separated by 12 nanometers in an organic crystal. The two molecules
      undergo a strong coherent dipole-dipole coupling that produces entangled sub- and
      superradiant states. Under intense laser illumination, both molecules are excited
      via a two-photon transition, and the fluorescence from this doubly excited system
      displays photon bunching. Our experimental scheme can be used to optically
      resolve molecules at the nanometer scale and to manipulate the degree of
      entanglement among them.

PMID- 12215652
TI  - Progression of vertebrate limb development through SHH-mediated counteraction of
      GLI3.
AB  - Distal limb development and specification of digit identities in tetrapods are
      under the control of a mesenchymal organizer called the polarizing region. Sonic
      Hedgehog (SHH) is the morphogenetic signal produced by the polarizing region in
      the posterior limb bud. Ectopic anterior SHH signaling induces digit duplications
      and has been suspected as a major cause underlying congenital malformations that
      result in digit polydactyly. Here, we report that the polydactyly of Gli3
      deficient mice arises independently of SHH signaling. Disruption of one or both
      Gli3 alleles in mouse embryos lacking Shh progressively restores limb distal
      development and digit formation. Our genetic analysis indicates that SHH
      signaling counteracts GLI3-mediated repression of key regulator genes, cell
      survival, and distal progression of limb bud development.

PMID- 12215653
TI  - Establishment and maintenance of a heterochromatin domain.
AB  - The higher-order assembly of chromatin imposes structural organization on the
      genetic information of eukaryotes and is thought to be largely determined by
      posttranslational modification of histone tails. Here, we study a 20-kilobase
      silent domain at the mating-type region of fission yeast as a model for
      heterochromatin formation. We find that, although histone H3 methylated at lysine
      9 (H3 Lys9) directly recruits heterochromatin protein Swi6/HP1, the critical
      determinant for H3 Lys9 methylation to spread in cis and to be inherited through
      mitosis and meiosis is Swi6 itself. We demonstrate that a centromere-homologous
      repeat (cenH) present at the silent mating-type region is sufficient for
      heterochromatin formation at an ectopic site, and that its repressive capacity is
      mediated by components of the RNA interference (RNAi) machinery. Moreover, cenH
      and the RNAi machinery cooperate to nucleate heterochromatin assembly at the
      endogenous mat locus but are dispensable for its subsequent inheritance. This
      work defines sequential requirements for the initiation and propagation of
      regional heterochromatic domains.

PMID- 12215654
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin toxicity in the zebrafish embryo: local
      circulation failure in the dorsal midbrain is associated with increased
      apoptosis.

PMID- 12215655
TI  - A physiologically based pharmacokinetic model for trichloroethylene in the male
      long-evans rat.
AB  - A physiologically based pharmacokinetic (PBPK) model for trichloroethylene (TCE)
      in the male Long-Evans (LE) rat was needed to aid in evaluation of neurotoxicity
      data collected in this rodent stock. The purpose of this study was to develop
      such a model with the greatest possible specificity for the LE rat. The PBPK
      model consisted of 5 compartments: brain, fat, slowly perfused tissue, rapidly
      perfused viscera, and liver. Partition coefficients (blood, fat, muscle, brain,
      liver) were determined for LE rats. The volumes of the brain, liver, and fat
      compartments were estimated for each rat, with tissue-specific regression
      equations developed from measurements made in LE rats. Vapor uptake data from LE
      rats were used for estimation of Vmaxc. As blood flow values for LE rats were not
      available, values from Sprague-Dawley (SD) and Fischer-344 (F344) rats were used
      in separate simulations. The resulting values of Vmaxc were used to simulate
      tissue (blood, liver, brain, fat) TCE concentrations, which were measured during
      (5, 20, 60 min) and after (60 min of TCE followed by 60 min of air) flow-through
      inhalation exposures of LE rats to 200, 2000, or 4000 ppm TCE. Simulation of the
      experimental data was improved by use of F-344 blood-flow values and the
      corresponding Vmaxc (8.68 mg/h/kg) compared to use of SD flows and the associated
      Vmaxc (7.34 mg/h/kg). Sensitivity analysis was used to determine those input
      parameters with the greatest influence on TCE tissue concentrations. Alveolar
      ventilation consistently (across exposure concentration, exposure duration, and
      target tissue) had the greatest impact on TCE tissue concentration. The PBPK
      model described here is being used to explore the relationship between measures
      of internal dose of TCE and neurotoxic outcome.

PMID- 12215656
TI  - Inhibition of human topoisomerase IIalpha by fluoroquinolones and ultraviolet A
      irradiation.
AB  - Some fluoroquinolone antibiotics (FQs) become toxic and mutagenic upon exposure
      to ultraviolet radiation (UV). Topoisomerase inhibition has been proposed as one
      possible mechanism involved in this photochemical genotoxicity. To study this
      reaction, inhibition of the human topoisomerase IIalpha enzyme by four FQs
      varying in photochemical genotoxic potency (Bay y3118 [y3118] > Lomefloxacin
      [Lmx] > Ciprofloxacin [Cpx] > Moxifloxacin [Mox]) was measured in vitro in the
      presence of UVA irradiation. None of the FQs inhibited topoisomerase IIalpha in
      the absence of irradiation. In contrast, with irradiation at 365 nm, the potent
      photochemically genotoxic y3118 produced strong inhibition of the enzyme by 15%
      and Cpx caused a weak 5% inhibition, but the more photochemically genotoxic Lmx
      only showed a transient inhibitory effect at one concentration and one
      irradiation dose. The photostable Mox had no effect with irradiation.
      Topoisomerase IIalpha inhibition by y3118 only occurred when the FQ, DNA, and
      enzyme were simultaneously present in the UVA-irradiated reaction mixture and was
      abolished in the absence of ATP, indicating the possible formation of a ternary
      structure. The y3118 photochemical topoisomerase inhibition correlated with the
      increased irradiation-mediated binding of radiolabeled FQ to DNA:topoisomerase
      complexes and was irreversible, like that of the topoisomerase poison, etoposide,
      without irradiation. The inhibitory effect of photoactivated y3118 on
      topoisomerase IIalpha was also observed in the presence of the antioxidant TEMPO,
      indicating that reactive oxygen species were not involved in the inhibition.
      These observations demonstrate that some but not all photochemically genotoxic
      FQs inhibit human topoisomerase IIalpha, possibly by UV-induced affinity of FQs
      to DNA:topoisomerase complexes.

PMID- 12215657
TI  - Lung tumor development in mice exposed to tobacco smoke and fed beta-carotene
      diets.
AB  - In human clinical trials it was found that the putative chemopreventive agent
      beta-carotene not only failed to protect active smokers against the carcinogenic
      action of tobacco smoke, but actually increased their risk of developing lung
      cancer. In preclinical animal studies, beta-carotene had been effective against
      some chemically induced cancers, but not against tumors in the respiratory tract.
      We exposed male strain A/J mice to tobacco smoke at a concentration of 140
      mg/m(3) of total suspended particulate matter, 6 h a day, 5 days a week, for
      either 4 or 5 months, followed by a recovery period in air for 4 or 5 months, or
      for 9 months without recovery period. beta-carotene was added in the form of
      gelatin beadlets to the AIN-93G diet either during or following tobacco smoke
      exposure at concentrations of 0.005, 0.05 and 0.5%. In the supplement-fed
      animals, plasma and lung levels of beta-carotene were higher than they were in
      animals fed control diets. Exposure to tobacco smoke increased rather than
      decreased plasma beta-carotene levels, but had no significant effect on lung
      levels. After 9 months, lung tumor multiplicities and incidence were determined.
      Tobacco smoke increased both lung tumor multiplicities and incidences, but beta
      carotene failed to modulate tumor development under all exposure conditions.
      Animal studies in a model of tobacco smoke carcinogenesis would thus have
      predicted the absence of any beneficial effects of beta-carotene supplementation
      in current or former smokers, but would have failed to anticipate the increase in
      lung cancer risk.

PMID- 12215658
TI  - Significance of the renal effects of ethyl benzene in rodents for assessing human
      carcinogenic risk.
AB  - In the two-year carcinogenicity study conducted by the National Toxicology
      Program (NTP) and reported in 1999, ethyl benzene administered by inhalation to
      Fischer 344 rats was associated with an increase in renal tubule tumors in males
      after standard evaluation of a single section of each rat's kidney, and in both
      males and females after evaluation of step-sectioned kidney. In the present
      study, the kidneys of all rats in the NTP bioassay were histopathologically
      reevaluated with the purpose of attempting to define a mode of action underlying
      the development of the renal tumors. In the reevaluation, the increases in renal
      tubule tumor incidence in the high-dose groups exposed to 750 ppm were confirmed,
      as well as increases in the precursor lesion, atypical tubule hyperplasia (ATH).
      The vast majority of the proliferative lesions were of basophilic type and, apart
      from three carcinomas in the high-dose males, either small adenomas or foci of
      ATH. There was also a marked exacerbation by the chemical of chronic progressive
      nephropathy (CPN), an age-related spontaneous disease involving both degenerative
      and regenerative components, in the high-dose males exposed to 750 ppm of ethyl
      benzene (68% of high-dose males with end-stage CPN versus 12% of control males),
      and a modest exacerbation in the high-dose females (8% of high dose versus 0% of
      controls). Almost all of the basophilic tumors occurred in rats with advanced,
      usually end-stage, CPN, and they were located in areas of parenchyma involved in
      the CPN disease process. Statistical analysis of the proliferative lesion and CPN
      data revealed a highly significant correlation between ATH/renal tumor incidence
      and end-stage CPN, and adjusting for end-stage CPN removed any statistically
      significant difference in renal tumor incidence between treated groups and
      controls. Careful examination of renal tubules revealed no evidence of renal
      tubule injury or increased mitotic activity that would support sustained
      cytotoxicity/cell regeneration as a mode of action for tumor development. An
      absence of granular casts and linear papillary mineralization discounted the
      possibility of alpha(2u)-globulin nephropathy as the primary underlying basis in
      male rats, even though subchronic studies revealed a modest accumulation of
      hyaline droplets in proximal tubules. Based on the close association of ATH and
      renal tumors with CPN, it was concluded that chemically induced exacerbation of
      CPN was the mode of action underlying the development of renal neoplasia, a
      pathway that is considered to have no relevance for extrapolation to humans.

PMID- 12215659
TI  - 17beta-estradiol is a hormonal regulator of mirex tumor promotion sensitivity in
      mice.
AB  - Mirex, an organochlorine pesticide, is a potent non-phorbol ester tumor promoter
      in mouse skin. Previous studies have shown that female mice are 3 times more
      sensitive to mirex tumor promotion than male mice and that ovariectomized (OVX)
      female mice are resistant to mirex promotion, suggesting a role for ovarian
      hormones in mirex promotion. To determine whether the ovarian hormone 17-beta
      estradiol (E2) is responsible for the sensitivity of female mice to mirex
      promotion, female mice were initiated with DMBA; 2 weeks later groups of mice
      were OVX and implants, with or without E2, were surgically implanted
      subcutaneously. These mice were treated topically twice weekly with mirex for 26
      weeks. E2 implanted OVX mice demonstrated high normal physiologic levels of serum
      E2 throughout the tumor promotion experiment. E2 implants restored by 80% the
      intact mirex-sensitive phenotype to the OVX mice. Consistent with a role for E2
      and ERalpha and ERbeta, treatment of DMBA-initiated female mice with topical ICI
      182,780, an estrogen-receptor antagonist, reduced mirex tumor multiplicity by
      30%. However, in cells co-transfected with ERalpha or ERbeta and estrogen
      responsive promoter reporter, mirex did not stimulate promoter reporter activity,
      suggesting that the promotion effect of mirex is downstream of ERalpha/beta.
      Finally, a tumor promotion study was conducted to determine whether E2 implants
      could increase the sensitivity of male mice to mirex promotion. E2 implants in
      male mice did increase sensitivity to mirex promotion; however, the implants did
      not produce the full female sensitivity to mirex tumor promotion. Collectively,
      these studies indicate that E2 is a major ovarian hormone responsible for mirex
      tumor promotion sensitivity in female mice.

PMID- 12215660
TI  - DNA arrays to monitor gene expression in rat blood and uterus following 17beta
      estradiol exposure: biomonitoring environmental effects using surrogate tissues.
AB  - We propose that gene expression changes in accessible tissues such as blood often
      reflect those in inaccessible tissues, thus offering a convenient biomonitoring
      method to provide insight into the effects of environmental toxicants on such
      tissues. In this pilot study, gene expression changes in peripheral blood
      leukocytes (PBL) were compared to those in the uteri of adult rats to identify
      genes that were altered in both tissues following estradiol treatment.
      Ovariectomized rats were treated with either 17beta-estradiol or vehicle control
      (corn oil) for 3 days. PBL and uterine RNAs were hybridized to arrays containing
      1185 genes. One hundred and ninety three genes were expressed in common between
      the PBL and uterus. Eighteen were changed significantly in both tissues, 9 of
      which were treatment- but not tissue-specific (e.g., jun-D, phospholipase A2,
      thymidine kinase). These results demonstrate that many genes are coexpressed
      between PBL and uterus, and that some are coregulated by estradiol. Given the
      limited number of genes examined in this study and the estimated size of other
      mammalian genomes, we conclude that many more genes will also be coregulated and
      suggest that accessible tissues such as PBL can serve as surrogate tissues for
      observing gene expression changes in inaccessible target tissues.

PMID- 12215661
TI  - Development of a physiologically based pharmacokinetic model for estradiol in
      rats and humans: a biologically motivated quantitative framework for evaluating
      responses to estradiol and other endocrine-active compounds.
AB  - A physiologically based pharmacokinetic (PBPK) model for estradiol (E2) in rats
      and humans (male and female) was developed to provide a quantitative tool for
      evaluating the importance of physiological parameters on E2 blood and tissue
      concentration time-course and for predicting blood and tissue concentrations in
      rats and humans. A hepatic extraction model was developed to evaluate the
      significance of plasma protein binding on the hepatic extraction of E2 and the
      approach was integrated into the E2 model. Sufficient data was available to
      parameterize and validate oral and iv routes. The E2 model simulations of E2
      blood and tissue concentrations compared well to experimental values. Estrogen
      receptor content strongly impacts distribution and elimination kinetics of E2 as
      well as tissue concentrations. The prolonged terminal elimination phase seen
      after iv bolus administration reflects the slow release of receptor bound E2 from
      tissues. E2 uptake behavior in the ovariectomized, but not intact rat uterus, was
      best described as diffusion-limited. Simulations with the hepatic extraction
      model predicted extensive binding of E2 to albumin (rat) and SHBG (sex-hormone
      binding globulin humans), although hepatic extraction does not appear to be
      restricted to the unbound fraction, implying that the total plasma E2
      concentration is important when considering hepatic uptake. Important
      determinants of E2 disposition are tissue ER content and binding affinity,
      nonreceptor binding proteins, vascular permeability, partition coefficients,
      hepatic blood flow, and extrahepatic metabolism. As an integral part of a
      research program, the quantitative framework developed for E2 can be extended to
      other endocrine-active compounds (EACs) and used to evaluate the biological
      activity of EACs.

PMID- 12215662
TI  - Evaluation of a 15-day screening assay using intact male rats for identifying
      steroid biosynthesis inhibitors and thyroid modulators.
AB  - An in vivo screening assay using intact adult male rats has been evaluated for
      its ability to detect four endocrine-active compounds (EACs) via oral (gavage)
      administration. The test compounds included the aromatase inhibitor fadrozole
      (FAD), the testosterone biosynthesis inhibitor ketoconazole (KETO), and the
      thyroid modulators phenobarbital (PB) and propylthiouracil (PTU). Three of the
      test compounds (KETO, PB, and PTU) have been previously evaluated in the 15-day
      intact male assay with compound administration via intraperitoneal injection
      (ip). For the current studies, male rats were dosed for 15 days via oral gavage
      and euthanized on the morning of test day 15. The endpoints evaluated included
      final body and organ weights (liver, thyroid gland, testes, epididymides,
      prostate, seminal vesicles with fluid, accessory sex gland unit [ASG]), serum
      hormone concentrations (testosterone [T], estradiol [E2], dihydrotestosterone
      [DHT], luteinizing hormone [LH,] follicle stimulating hormone [FSH], prolactin
      [PRL], T(3), T(4), thyroid stimulating hormone [TSH]), and histopathology of the
      testis, epididymis, and thyroid gland; positive results for each endpoint are
      described below. In addition, an evaluation of immune system endpoints (humoral
      immune function, spleen and thymus weights, and spleen cell number) was conducted
      on a subset of animals dosed with either KETO or PB. FAD and KETO decreased the
      weights for the androgen-dependent tissues and caused similar patterns of
      hormonal alterations (decreased serum T and DHT; increased serum FSH and/or LH).
      In addition, KETO caused spermatid retention. For FAD and KETO, effects on
      thyroid parameters were not indicative of thyroid toxicity. PB and PTU caused
      thyroid effects consistent with thyroid modulators (increased thyroid weight,
      decreased serum T(3) and T(4), increased serum TSH, thyroid follicular cell
      hypertrophy/hyperplasia, and colloid depletion). In addition, PB increased
      relative liver weight and altered reproductive hormone concentrations (decreased
      serum DHT, PRL, LH; increased serum E2). Orally administered KETO and PB did not
      alter the primary humoral immune response to sheep red blood cells (SRBC),
      although spleen weights were increased at the highest doses for both compounds.
      In the current study, all four test substances were identified as endocrine
      active. The effects that were observed in the current study via oral (gavage)
      compound administration were similar to the responses that were observed by the
      ip route in previous studies for KETO, PB, and PTU. Overall, the sensitivity
      (i.e., the dose required to elicit similar magnitude responses) between the ip
      and oral routes of administration were similar for the three EACs that were
      examined by both routes of administration. This article, in addition to the > 20
      compounds that have already been examined using the 15-day intact male assay,
      supports this assay as a viable screening assay for detecting EACs, and also
      illustrates that the ability to identify EACs using the intact male assay will be
      equivalent regardless of the route of compound administration.

PMID- 12215663
TI  - Evaluation of a 15-day screening assay using intact male rats for identifying
      antiandrogens.
AB  - An in vivo screening assay using intact adult male rats has been evaluated for
      its ability to detect six antiandrogenic compounds via oral administration. The
      test compounds included cyproterone acetate (CPA), flutamide (FLUT), p,p'-DDE
      (DDE), di-n-butyl phthalate (DBP), linuron (LIN), and vinclozolin (VCZ). Two of
      the test compounds (DDE and FLUT) have been previously evaluated in the 15-day
      intact male assay with compound administration via intraperitoneal injection
      (ip). For the current studies, male rats were dosed for 15 days via oral gavage
      and euthanized on the morning of test day 15. The endpoints evaluated included
      final body and organ weights (liver, thyroid gland, testes, epididymides,
      prostate, seminal vesicles with fluid, accessory sex gland unit [ASG]), serum
      hormone concentrations (testosterone [T], estradiol [E2], dihydrotestosterone
      [DHT], luteinizing hormone [LH], follicle stimulating hormone [FSH], prolactin
      [PRL], T(3), T(4), and thyroid stimulating hormone[TSH]), and histopathology of
      the testis, epididymis, and thyroid gland; positive results for each endpoint are
      described below. In addition, an evaluation of immune system endpoints (humoral
      immune function, spleen and thymus weights, and spleen cell number) was conducted
      on a subset of animals dosed with either DDE or FLUT. All six endocrine-active
      compounds (EACs) increased relative liver weight. FLUT and VCZ caused the typical
      pattern for an androgen receptor (AR) antagonist, although not all endpoints were
      statistically significant for VCZ: decreased ASG weights, hormonal alterations
      (increased T, DHT, LH, and FSH), and induced Leydig cell hypertrophy and/or
      hyperplasia. CPA caused effects consistent with its mixed AR
      antagonist/progesterone receptor agonist activity: it decreased ASG weights,
      caused hormonal alterations (increased T and E2; decreased FSH), and caused
      spermatid retention. DBP, a compound with antiandrogen-like activity via a
      nonreceptor mediated mechanism, caused hormonal alterations (decreased T, DHT,
      and E2; increased LH, FSH, and PRL) and induced general testicular degeneration.
      LIN, a weak AR antagonist, decreased ASG weights, caused hormonal alterations
      (decreased T, DHT, and LH; increased E2), and caused spermatid retention. Unlike
      the other AR antagonists evaluated, DDE, a weak AR antagonist, did not alter
      reproductive parameters. All six antiandrogens caused some effects on thyroid
      parameters, although only CPA, DDE, and VCZ caused results consistent with a
      potential thyroid-modulator. FLUT and DDE did not alter the primary humoral
      immune response to SRBC, spleen or thymus weights, or spleen cell number. In the
      current study, 5 of the six test substances were identified as endocrine-active
      substances consistent with their known/proposed mechanism(s) of action. The
      effects that were observed in the current study via oral (gavage) compound
      administration were similar to the responses that were observed by the ip route
      in previous studies for DDE and FLUT. This report, in addition to the > 20
      compounds that have already been examined using the 15-day intact male assay,
      supports this assay as a viable screening assay for detecting EACs, and also
      illustrates that the ability to identify EACs using the intact male assay will be
      equivalent regardless of the route of compound administration.

PMID- 12215664
TI  - Mortality in dioxin-exposed mice infected with influenza: mitochondrial toxicity
      (reye's-like syndrome) versus enhanced inflammation as the mode of action.
AB  - Increased mortality following influenza A infection was reported in B6C3F1 mice
      exposed to a low (0.01 micro g/kg) dose of dioxin. However, mortality was not
      associated with increased viral load and antibody titers to the virus were not
      decreased at doses of TCDD < or = 10 micro g/kg, suggesting that viral
      overgrowth, secondary to immunosuppression, was not the proximate cause of death.
      We tested the hypothesis that mitochondrial toxicity and dysfunction, similar to
      Reye's syndrome (RS) in humans, is responsible for increased mortality in dioxin
      exposed, infected B6C3F1 female mice, based on similarities in the biochemical
      and immunological events that occur in RS and in TCDD-exposed animals. Endpoints
      were also included to test the hypothesis that increased pulmonary inflammation
      following dioxin exposure, in the absence of mitochondrial toxicity, was
      associated with increased mortality. Dose-related effects of TCDD alone,
      infection with influenza A alone, and combined TCDD exposure/influenza infection
      were evaluated. Mice were given a single ip injection of 0, 0.001, 0.01, 0.1, or
      1.0 micro g TCDD/kg, 7 days before infection by intranasal instillation of an
      estimated LD(10-20) of influenza A Hong Kong/8/68 (H3N2) and were terminated 1,
      7, and 10 days after infection. Serum, bronchoalveolar lavage fluid (BALF), and
      lung tissue were collected for various measurements, including clinical
      chemistries, cell counts, cytokine analysis, and viral titers. Exposure to < or =
      1.0 micro g TCDD/kg did not increase mortality; virus titers were similar at all
      doses of TCDD and there was no dioxin-related effect on serum NH(3) or glucose
      concentrations, two prominent indicators of the altered mitochondrial oxidative
      metabolism typically observed in RS. A study was therefore conducted over a wider
      range of TCDD doses. A single injection of 0, 0.025, 0.5, or 10 micro g TCDD/kg
      preceded infection by 7 days; subgroups of noninfected control and highest dose
      group (10 micro g TCDD/kg) mice were also evaluated for biochemical and
      immunological endpoints on the equivalent of infection day 4 to provide baseline
      data. Five days after infection the same endpoints described above were
      evaluated. The 10 micro g TCDD/kg dose increased mortality, but once again did
      not increase virus titer; as in previous experiments, serum biochemistry
      endpoints did not support mitochondrial dysfunction. These results suggest that
      RS is an unlikely explanation for increased influenza mortality in TCDD-exposed
      mice. Rather, constituents in BALF implicate increased pulmonary inflammation as
      the mode of TCDD action.

PMID- 12215665
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin causes alterations in lymphocyte development
      and thymic atrophy in hemopoietic chimeras generated from mice deficient in
      ARNT2.
AB  - It is well established that dioxins cause a variety of toxic effects and
      syndromes including alterations of lymphocyte development. Exposure to the
      prototypical dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to severe
      thymic atrophy in all species studied. It has been shown that most of this
      toxicity is due to TCDD binding to and activating the aryl hydrocarbon receptor
      (AHR). Upon activation, the AHR enters the nucleus, dimerizes with the AHR
      nuclear translocator (ARNT), and this heterodimer modulates a number of genes
      that mediate toxicity. The AHR and ARNT are members of the basic-helix-loop-helix
      Per, ARNT, and Sim homology (bHLH-PAS) family of transcription factors. In this
      study, we wanted to determine if another bHLH-PAS transcription factor, ARNT2,
      which has high amino acid sequence identity to ARNT and has been shown to
      dimerize with the TCDD-activated AHR, is involved in mediating TCDD's effect on
      lymphocyte development. We determined by RT-PCR that ARNT2 is expressed at a low
      level in whole thymus, thymocytes, and bone marrow lymphocytes. We created
      hemopoietic chimeras by lethally irradiating C57BL/6 mice and reconstituting them
      with fetal liver stem cells that either have or are deficient in a portion of
      chromosome 7 that contains ARNT2. Regardless of whether chimeras possessed or
      lacked this chromosome fragment, equal sensitivity to TCDD-induced thymic atrophy
      was observed despite expression of ARNT2 in the thymus. Furthermore, the absence
      of ARNT2 (or any other genes found on this portion of chromosome 7) did not
      confer any protection against TCDD-induced alterations in bone marrow B-cell
      subsets. These data indicate that in this model system the effects of TCDD
      induced thymic atrophy and alterations in B-cell maturation are not dependent on
      an AHR-ARNT2 heterodimer.

PMID- 12215666
TI  - Screening of dioxin-like toxicity equivalents for various matrices with wildtype
      and recombinant rat hepatoma H4IIE cells.
AB  - Determination of dioxin-like compounds utilizing in vitro bioassays such as
      ethoxyresorufin-O-deethylase (EROD) or chemical-activated luciferase expression
      (DR-CALUX) is an important tool to evaluate their Ah receptor-mediated toxic
      effects. The aim of this study is to describe advantages and limitations of these
      bioassays using rat hepatoma (H4IIE) wildtype and recombinant H4IIE cells in a 96
      well microtiter plate format. We are using these bioassays for the evaluation of
      relative responses (REP) from several congeners of dioxins (e.g., 2,3,4,7,8-PCDF)
      or dioxin-like compounds (PCB-126, 2,3,4,7,8-PBDF) to 2,3,7,8-TCDD. In addition,
      total toxic equivalency factors (TEFs) of mixtures of these dioxin-like compounds
      from several kinds of matrices such as feed, sediment, or thermal waste residues
      are measured by both bioassays and additional chemical analysis. These samples
      were measured in a cross-validation study between two laboratories using the DR
      CALUX technology in comparison to the H4IIE-EROD assay and chemical analysis.
      Improvement of the quality criteria of the newly developed DR-CALUX bioassays in
      comparison to the EROD bioassay was demonstrated (higher coefficient of
      determination r(2); better repeatability of TCDD and samples), while induction
      factor, limit of detection, and limit of quantification have been similar. The
      tested samples showed positive responses in both bioassays using different
      kinetics (EROD: 72 h; DR-CALUX: 24 h). Ratio of measured toxicity equivalent
      (TEQ) values varied around mean values of 0.89 (comparing both DR-CALUX
      laboratories, ranging from 0.68-3.1), 2.0 (comparing EROD and DR-CALUX, ranging
      from 0.57-8.1), and 1.6-2.5 (comparing EROD-TEQ and I-TEQ, mean 1.6, ranging from
      1.0-3.9; for DR-CALUX/I-TEQ, 2.5; 0.61-8.3), respectively. This demonstrates that
      these bioassays can be used as alternative screening technology for monitoring I
      TEQ values in various standards and matrices.

PMID- 12215667
TI  - Effects of troglitazone on HepG2 viability and mitochondrial function.
AB  - Troglitazone (TRO), a member of the thiazolidinedione class of drugs, has been
      associated with hepatotoxicity in patients. The following in vitro study was
      conducted to investigate the effects of TRO on mitochondrial function and
      viability in a human hepatoma cell line, HepG2. TRO induced a concentration- and
      time-dependent increase in cell death, as measured by lactate dehydrogenase
      release. Exposure to 50 or 100 micro M TRO produced total loss of cell viability
      within 5 h. Preincubation of HepG2 cells with P450 inhibitors did not
      significantly protect against TRO-induced cell death suggesting that P450
      metabolism was not required to induce cell death. Preincubation with the
      mitochondrial permeability transition inhibitor, cyclosporin A, provided complete
      protection against TRO-induced cell death. Our results also indicated that TRO
      produced concentration-dependent decreases in cellular ATP levels and
      mitochondrial membrane potential (MMP). Ultrastructural analysis demonstrated
      that TRO induced mitochondrial changes at concentrations of > or =10 micro M
      after 2 h. Decreased MMP and altered mitochondrial morphology occurred at time
      points that preceded cell death and at sublethal concentrations of TRO. These
      observations in HepG2 cells suggest that TRO disrupts mitochondrial function,
      leading to mitochondrial permeability transition and cell death.

PMID- 12215669
TI  - Tea catechins protect against lead-induced cytotoxicity, lipid peroxidation, and
      membrane fluidity in HepG2 cells.
AB  - Recent studies have shown that lead causes oxidative stress by inducing the
      generation of reactive oxygen species (ROS) and reducing the antioxidant defense
      system of cells. This suggests that antioxidants may play an important role in
      the treatment of lead poisoning as a kind of excellent scavenger of free radicals
      and chelator of heavy metal. Whether tea catechins have protective effects
      against oxidative stress after lead treatment in cell systems remains unclear.
      The present study was designed to elucidate if tea catechins have any protective
      effects on lipid peroxidation damage in lead-exposed HepG2 cells. Exposure of
      HepG2 cells to Pb(++) decreased cell viability and stimulated lipid peroxidation
      of cell membranes as measured by the thioburbituric acid reaction. Electron spin
      resonance (ESR) spin-labeling studies indicated that lead exposure could decrease
      the fluidity in the polar surface of cell membranes. Tea catechin treatment
      significantly increased cell viability, decreased lipid peroxidation levels, and
      protected cell membrane fluidity in lead-exposed HepG2 cells in a concentration
      dependent manner. The galloylated catechins showed a stronger effect than
      nongalloylated catechins. Cotreatment with (-)-epigallocatechin gallate (EGCG)
      and (-)-epicatechin (EC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin
      gallate (EGCG) showed a synergistically protective effect. The results suggest
      that tea catechin supplementation may have a role to play in modulating oxidative
      stress in lead-exposed HepG2 cells.

PMID- 12215668
TI  - Peroxisome proliferators do not activate the transcription factors AP-1, early
      growth response-1, or heat shock factors 1 and 2 in rats or hamsters.
AB  - Peroxisome proliferators (PPs) cause hepatomegaly, peroxisome proliferation, and
      hepatocarcinogenesis in rats and mice, whereas hamsters are less responsive to
      these compounds. PPs increase peroxisomal beta-oxidation and P4504A subfamily
      activity, which have been hypothesized to result in oxidative stress. Work in our
      laboratory indicated that differential modulation of the redox-sensitive
      transcription factor NF-kappaB may contribute to the resulting difference in
      species susceptibility following PP administration. Therefore, we hypothesized
      that other redox-sensitive transcription factors such as AP-1, early growth
      response gene 1 (Egr-1), and heat-shock factors 1 and 2 (HSF1/2) may also be
      alternatively activated in differentially susceptible species. Accordingly, we
      measured the activation of these transcription factors using gel mobility shift
      assays, with hepatic nuclear extracts derived from rats and Syrian hamsters fed
      two doses of three peroxisome proliferators (dibutyl-phthalate [DBP], gemfibrozil
      and Wy-14,643) for 6, 34, or 90 days. Although changes were observed at various
      time points, no consistent, dose-responsive changes were observed in the DNA
      binding activities of these transcription factors following PP treatment. The
      lack of increased binding of AP-1, Egr-1, and HSFs suggests that these factors
      are not involved in increased cell proliferation following PP administration,
      although we cannot rule out that these factors are activated at earlier time
      points than those examined in this study.

PMID- 12215670
TI  - Acute and repeated restraint stress have little effect on pyridostigmine toxicity
      or brain regional cholinesterase inhibition in rats.
AB  - Pyridostigmine, a carbamate cholinesterase (ChE) inhibitor, has been used for
      decades in the treatment of the autoimmune disorder myasthenia gravis and was
      used prophylactically to protect soldiers from possible organophosphorus nerve
      agent exposures during the Persian Gulf War. Pyridostigmine is a charged,
      quaternary compound and thus would not be expected to easily pass the blood-brain
      barrier. Some studies have suggested, however, that stress may alter blood-brain
      barrier integrity and allow pyridostigmine to enter the brain. We evaluated the
      effects of acute and repeated restraint stress on functional signs of cholinergic
      toxicity (i.e., autonomic dysfunction and involuntary movements) and brain
      regional cholinesterase inhibition following either acute or repeated
      pyridostigmine exposures. The acute, oral maximum-tolerated dosage (MTD) of
      pyridostigmine was estimated at 30 mg/kg. Peak ChE inhibition in whole blood
      occurred from 0.5 to 4 h after MTD exposure, whereas minimal (<20%) brain ChE
      inhibition was noted. For acute restraint studies, rats were either (1)
      restrained for 90 min and then given pyridostigmine (30 mg/kg, po), (2) given
      pyridostigmine and immediately restrained for 60 min, or (3) restrained for 3 h,
      given pyridostigmine, and restrained for an additional 60 min. In all cases, rats
      were evaluated for cholinergic toxicity (SLUD signs and involuntary movements)
      and sacrificed 1 h after pyridostigmine treatment. Plasma corticosterone was
      significantly elevated immediately after a single 60-min session of acute
      restraint stress, but returned to control levels by 1 and 3 h later.
      Pyridostigmine-induced toxicity was not enhanced nor was brain ChE inhibition
      altered by acute restraint stress. Blood-brain barrier permeability, assessed by
      accumulation of horseradish peroxidase in brain regions following intracardiac
      injection, was not increased by restraint stress. For repeated restraint studies,
      rats were given pyridostigmine (0, 3, or 10 mg/kg/day) immediately prior to daily
      restraint (60 min) for 14 consecutive days. Plasma corticosterone was elevated at
      1 and 7 days but not at 14 days. Pyridostigmine-treated rats in both dosage
      groups exhibited slight signs of toxicity for the first 3-5 days, after which
      cholinergic signs dissipated. Repeated restraint had little effect on functional
      signs of pyridostigmine toxicity, however. Whole blood and diaphragm ChE were
      markedly reduced 1 h after the last treatment, but stress had no influence on ChE
      inhibition in either peripheral or central tissues. The results suggest that
      acute and repeated restraint stress have little effect on pyridostigmine
      neurotoxicity or apparent entry of pyridostigmine into the brain.

PMID- 12215671
TI  - Evaluation of the developmental toxicity of formamide in New Zealand white
      rabbits.
AB  - Naturally mated female New Zealand White (NZW) rabbits (24/group) received
      formamide (35, 70, or 140 mg/kg/day) or vehicle (1 ml/kg deionized/distilled
      water) by gavage on gestational days (GD) 6 through 29. The study was conducted
      using a 2-replicate design. Maternal food consumption (absolute and relative),
      body weight, and clinical signs were monitored at regular intervals throughout
      gestation. One and four maternal deaths occurred at the low and high doses,
      respectively. Abortions or early deliveries were noted in 0, 2, 2, and 8 females
      in the 0, 35, 70, and 140-mg/kg/day dose groups, respectively. Other clinical
      signs associated with formamide exposure were minimal: primarily reduced or
      absent fecal output at the high dose (2-13 animals/day). Also at the high dose,
      maternal body weight was significantly depressed on GD 21, 24, and 27 (87-90% of
      the control value); maternal body weight gain was significantly reduced for GD 12
      to 15, 18 to 21, and 21 to 24 (treated animals gained less than 1 g, or lost up
      to 100 g). In addition, maternal body weight gain was reduced at the middle dose
      for GD 18 to 21. Maternal body weight gain, corrected for gravid uterine weight,
      was unaffected. Relative maternal food consumption in the high-dose group was 34
      59% of control intake from GD 12 through GD 24, but was comparable to controls
      thereafter. At termination (GD 30), confirmed-pregnant females (9-20 per group)
      were evaluated for clinical status, liver weights, and gestational outcome; live
      fetuses were examined for external, visceral, and skeletal malformations and
      variations. Maternal liver weight (absolute or relative to body weight) was
      unaffected by treatment, but gravid uterine weight at the high dose was 71% of
      the control value. A significantly increasing trend was noted for the percent non
      live implants per litter. In addition, although not statistically significant
      from the control group, the values for the percent late fetal deaths per litter
      and percent non-live implants per litter in the 140-mg/kg/day group were higher
      than maximum historical values, suggesting an increase in late gestational deaths
      in the surviving high-dose animals. Formamide decreased the mean number of live
      fetuses per litter at the high dose to 66% of the control value. Mean fetal body
      weight per litter for males and the sexes combined was significantly decreased at
      the high dose; mean female fetal body weight was also decreased, although the
      difference did not reach statistical significance. There was no effect of
      treatment on the incidence of external, visceral, or skeletal malformations or
      variations in animals surviving to scheduled necropsy. In summary, the no
      observed-adverse-effect level (NOAEL) for maternal toxicity was 70 mg/kg/day and
      the lowest-observed-adverse-effect level (LOAEL) was 140 mg/kg/day under the
      conditions of this study. Similarly, the NOAEL for developmental toxicity was 70
      mg/kg/day and the LOAEL was 140 mg/kg/day.

PMID- 12215672
TI  - Microtubules of the mouse testis exhibit differential sensitivity to the
      microtubule disruptors Carbendazim and colchicine.
AB  - The testicular toxicant benomyl and its metabolite, carbendazim cause
      reproductive damage to the rat, an early sign of which is sloughing of germ cells
      with associated Sertoli cell fragments. However, the sensitivity of other
      mammalian species to these benzimidazole compounds is not clear. In this study,
      the effects of carbendazim and colchicine, a known microtubule disruptor, on the
      mouse seminiferous epithelium were characterized, and the amount of carbendazim
      reaching the mouse testis was measured. Testes were assessed for histological
      effects 3 h and 6 h after administration of carbendazim (2000 mg/kg, ip), and 6 h
      after intratesticular administration of either a low or high dose (5.3 or 117.6
      micro g/g testis) of colchicine. Carbendazim caused no signs of histological
      damage to the mouse testis, and the microtubule cytoskeleton was intact and
      identical to controls based on immunostaining with tyrosinated alpha tubulin and
      beta tubulin antibodies. Similarly, the seminiferous epithelium of mouse testis
      was undamaged and the microtubule cytoskeleton was intact after a low dose of
      colchicine, while a comparable dose of colchicine injected into rat testis caused
      marked toxicity. However, mouse testes did show microtubule disruption and severe
      germ cell sloughing after administration of a high dose of colchicine. The amount
      of carbendazim measured in mouse testis was 375 nmol/g testis, which is higher
      than the value measured in rat testis after a toxic dose of carbendazim.
      Therefore, carbendazim reaches the mouse testis at or above levels measured in
      the rat, yet the mouse is apparently insensitive to this microtubule disrupting
      agent.

PMID- 12215673
TI  - HSP90alpha, HSP90beta, and p53 expression following in vitro hyperthermia
      exposure in gestation day 10 rat embryos.
AB  - The studies presented here are aimed at understanding the expression of p53,
      HSP90alpha, and HSP90beta in gestation day (GD) 10 CD rat embryos. GD 10 rat
      embryos were exposed in vitro to 37 degrees C or 42 degrees C for 15 min, then
      cultured at 37 degrees C for 0.5, 1, 3, or 5 h. Immunohistochemistry was
      performed on formalin-fixed, paraffin embedded, sectioned embryos for p53,
      HSP90alpha, or HSP90beta expression. p53 expression was minimal in control
      embryos but was induced with heat exposure. Maximum expression of p53 was
      observed in rostral tissues, e.g., the optic vesicle, rostral neuroepithelium,
      and mature (rostral) somites 3 and 5 h after heat exposure. Expression of p53 in
      the caudal region, such as in mid and caudal neuroepithelium, immature (caudal)
      somites, and presomitic mesoderm, was moderate compared to rostral areas. No p53
      expression was observed in the heart under any condition. The rostral-caudal
      gradient of p53 expression was not observed for HSP90alpha expression. HSP90alpha
      was induced in heat-exposed embryos beginning at 1 h, predominantly in neural
      tube and optic vesicle. Moderate but increased expression was observed in the
      somites of heat-exposed embryos at 3 and 5 h. Expression of p53 was primarily
      nuclear while HSP90alpha expression was mostly cytoplasmic. No clear association
      was observed between heat-induced HSP90alpha and p53 expression. HSP90beta was
      expressed extensively in control and heat-exposed embryos. Results indicate that
      heat induces p53 and HSP90alpha expression, but not HSP90beta expression, and
      that HSP90alpha induction is not likely to be involved in p53 regulation in
      mammalian embryos.

PMID- 12215674
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in the zebrafish embryo: local
      circulation failure in the dorsal midbrain is associated with increased
      apoptosis.
AB  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on local circulation and
      apoptosis in the midbrain were investigated in zebrafish (Danio rerio) embryos
      during early development. Embryos were exposed to TCDD from 24 h post
      fertilization (hpf) until observation, in water maintained at 28.5 degrees C.
      TCDD decreased blood flow in the mesencephalic vein, the only vessel perfusing
      the dorsal midbrain of the embryo. At 50 hpf, blood flow was maximally reduced in
      this vessel and gradually returned to the control level at 60 hpf. In contrast,
      blood flows in the trunk and in other vessels of the head of the embryo did not
      significantly change until 72 hpf. Furthermore, TCDD exposure caused apoptosis in
      the midbrain at 60 hpf, and the TCDD dose response relationship for this effect
      was similar to that for reduced blood flow in the mesencephalic vein at 50 hpf.
      The effects of TCDD on apoptosis in the midbrain, but not on blood flow, were
      abolished by Z-VAD-FMK, a general caspase inhibitor. TCDD effects on both
      endpoints were mimicked by beta-naphthoflavone (BNF), an aryl hydrocarbon
      receptor (AHR) agonist, and almost abolished by concomitant exposure to TCDD and
      alpha-naphthoflavone (ANF), an AHR antagonist. Concomitant exposure to TCDD and
      either an inhibitor of cytochrome P450 (CYP) (SKF525A or miconazole) or an
      antioxidant (N-acetylcysteine or ascorbic acid) inhibited these effects of TCDD.
      The incidence of apoptosis in the midbrain was inversely related to blood flow in
      this brain region following these various treatments and graded TCDD exposure
      concentrations (r = -0.91). The same range of TCDD exposure concentrations that
      reduced blood flow and increased apoptosis in the midbrain greatly enhanced CYP1A
      mRNA expression and immunoreactivity at 50 hpf in endothelial cells of blood
      vessels including the mesencephalic vein and the heart, but not the brain
      parenchyma. Taken together, these results suggest that TCDD induces apoptosis in
      the midbrain of the zebrafish embryo secondary to local circulation failure,
      which could be related to AHR activation, induction of CYP1A, and oxidative
      stress.

PMID- 12215675
TI  - Critical windows of vulnerability for effects of 2,3,7,8-tetrachlorodibenzo-p
      dioxin on prostate and seminal vesicle development in C57BL/6 mice.
AB  - A single maternal dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gestation
      day (GD) 13 can greatly impair ventral prostate, dorsolateral prostate, anterior
      prostate, and seminal vesicle development in wild-type C57BL/6 mice. The
      developmental stages at which these organs are most sensitive to TCDD exposure
      have now been investigated. Pregnant mice were dosed orally with 5 micro g
      TCDD/kg or vehicle on GD 13, and their pups were fostered at birth to dams of the
      same treatment or cross-fostered to dams of the opposite treatment. Additional
      males had in utero and lactational TCDD exposure following maternal dosing on GD
      16. Organ weights and secretory protein, cytokeratin 8, and cyclophilin mRNA
      expression were determined at 35 days of age. Effects of TCDD on ventral prostate
      development were due primarily to in utero exposure; the critical window was
      between GD 13 and birth. Dorsolateral prostate development was inhibited about
      equally by in utero or lactational exposure, and vulnerability did not begin
      until GD 16. Anterior prostate development was also affected by both in utero and
      lactational TCDD exposure, particularly the former. Vulnerability began before GD
      16 and continued into postnatal life. Seminal vesicle development was essentially
      unaffected by in utero or lactational exposure alone but was significantly
      inhibited by combined exposure, regardless of whether dams were dosed on GD 13 or
      16. In summary, the time during which each organ was most vulnerable to TCDD
      exposure varied from one organ to another. These findings provide insights into
      the developmental processes that TCDD inhibits in each organ, and demonstrate
      that TCDD inhibits ventral prostate development before this organ first appears,
      presumably via effects on the urogenital sinus. The observation that in utero
      TCDD exposure (alone) inhibited development of each prostate lobe is significant
      because previous studies have shown that little TCDD is transmitted to mice
      before birth.

PMID- 12215676
TI  - Activation of human epithelial lung a549 cells by the pollutant sodium sulfite:
      enhancement of neutrophil adhesion.
AB  - Air pollutant exposure may induce deterioration of respiratory health.
      Concentrations of air particles, ozone, nitrogen dioxide, sulfur dioxide, and
      sulfate are among the players involved in the initiation and/or exacerbation of
      lung diseases. We have previously documented that the pollutant sodium sulfite
      (Na(2)SO(3)) is a human neutrophil agonist. To date, there is no evidence in the
      literature that Na(2)SO(3) can activate epithelial lung cells. In the present
      study, we found that Na(2)SO(3) (0.01-10 mM) induces tyrosine phosphorylation
      events and interleukin-8 production in human epithelial lung A549 cells. In
      addition, we found that Na(2)SO(3) did not promote A549 cell apoptosis as
      assessed by the degradation of the cytoskeletal gelsolin protein and by FITC
      annexin-V binding. Human neutrophil adhesion to Na(2)SO(3)-induced A549 cells was
      increased when compared with untreated A549 cells. As assessed by flow cytometry,
      cell surface expression of intercellular adhesion molecule (ICAM)-1, ICAM-3, and
      vascular cell adhesion molecule-1 (VCAM-1) on A549 cells was not affected by
      Na(2)SO(3). We conclude that Na(2)SO(3) can activate A549 cells. In addition, we
      conclude that neutrophil adhesion to Na(2)SO(3)-induced A549 cells is increased
      via an ICAM-1-, ICAM-3-, and VCAM-1-independent mechanism.

PMID- 12215677
TI  - Identification of pyridine compounds in cigarette smoke solution that inhibit
      growth of the chick chorioallantoic membrane.
AB  - Based on prior work, we hypothesized that cigarette smoke contains chemicals that
      can inhibit growth of the chick chorioallantoic membrane (CAM). In this study,
      gas chromatography and mass spectrometry were used to identify 12 pyridine
      derivatives in the inhibitory fractions of smoke eluted from solid phase
      extraction cartridges. These pyridine derivatives were further studied
      individually in dose response experiments to determine their effects on CAM
      growth. A correlation was observed between the functional group substitutions on
      pyridine and the relative toxicity of each pyridine derivative. In the CAM growth
      assay, pyridine derivatives with single methyl or single ethyl substitutions had
      lowest observed adverse effect levels (LOAELs) of 5 x 10(-9) and 5 x 10(-12) M,
      respectively. Other pyridine derivatives and pyridine itself had LOAELs in the
      micromolar range. One of the most inhibitory derivatives, 3-ethylpyridine, was
      studied further and inhibited cell proliferation, as measured by BrdU
      incorporation. Since 3-ethylpyridine inhibited growth at picomolar doses and is
      added to consumer products including cosmetics, food, drinks, and tobacco, it
      will be important to perform further toxicological testing to determine its
      effect on human health.

PMID- 12215678
TI  - Differential relationship between the carbon chain length of jet fuel aliphatic
      hydrocarbons and their ability to induce cytotoxicity vs. interleukin-8 release
      in human epidermal keratinocytes.
AB  - Jet fuels are complex mixtures of hydrocarbons known to cause dermal toxicity and
      to increase the release of proinflammatory cytokines by human epidermal
      keratinocytes (HEK). However, the dermatotoxic effects of individual hydrocarbons
      remain unclear. Since aliphatic hydrocarbons make up more than 80% of the
      hydrocarbons formulated in jet fuels, the objective of this study was to assess
      acute cytotoxicity and IL-8 release induced by individual aliphatic hydrocarbons
      without a vehicle. Ten aliphatic hydrocarbons with carbon (C) chain lengths
      ranging from 6 to 16 were dosed neat on HEK grown on 96-well plates. Acute
      exposure (1, 5, and 15 min) to aliphatic hydrocarbons significantly increased HEK
      mortality such that the increase in cytotoxicity corresponded with the decrease
      in carbon chain length. Extended exposure time did not increase cytotoxicity
      significantly until 15 min of exposure by short-chain hydrocarbons (C < or = 11).
      There were differences between the aliphatic hydrocarbons with respect to their
      effects on IL-8 release. IL-8 concentration was increased significantly by 3- to
      10-fold, with the highest increase found after exposure to hydrocarbons in the C9
      C13 range. These studies indicated that individual aliphatic hydrocarbons are
      toxic to HEK cells and are capable of inducing proinflammatory cytokines. Higher
      cytotoxicity by shorter-chain aliphatic hydrocarbons did not correlate to
      increased ability to stimulate IL-8 release, which peaked at mid-chain lengths,
      suggesting a different structure-activity relationship for these two
      toxicological endpoints in keratinocyte cell cultures.

PMID- 12215679
TI  - Comparative gavage subchronic toxicity studies of o-chloroaniline and m
      chloroaniline in F344 rats and B6C3F1 mice.
AB  - ortho-Chloroaniline (o-CA) andmeta-chloroaniline (m-CA) are chemical
      intermediates for pigment production in the textile industry. Comparative
      subchronic gavage studies were conducted to determine the effect of structure on
      toxicity.o-CA orm-CA was administered to 10 animals/sex/species in deionized
      water at dosages of 0, 10, 20, 40, 80, and 160 mg/kg for 13 weeks. Blood samples
      for clinical pathology were collected after 3 and 23 days in rats and at study
      termination (Day 93) in rats and mice. No mortalities occurred that could be
      directly attributed to treatment. Transient clinical signs of toxicity observed
      after dosing included cyanosis in rats and ataxia and tremors in mice.
      Methemoglobin formation was directly related to dosage (rats and mice) and
      duration of treatment (rats). At study termination, Heinz body formation in
      erythrocytes in association with decreased hemoglobin, hematocrit, and red blood
      cell count was a prominent treatment-related effect. Enlarged spleens (gross
      necropsy observation) and increased spleen weight were treatment effects of each
      chemical in both species. Microscopic lesions typical of increased red blood cell
      production were found in hematopoietic tissues (bone marrow, spleen, and liver),
      while lesions due to increased red cell destruction were found in these tissues
      and also the kidneys (rats). Microscopic changes were more frequently seen and
      severe, and involved more body organs, in rats than mice, and in m-CA-treated
      animals thano-CA-treated animals. Sex differences in lesion incidence/severity
      were not evident.

PMID- 12215680
TI  - Toxicity of ammonium perfluorooctanoate in male cynomolgus monkeys after oral
      dosing for 6 months.
AB  - Ammonium perfluorooctanoate (APFO) is a processing aid in the production of
      fluoropolymers that has been shown to have a long half-life in human blood. To
      understand the potential toxicological response of primates, groups of male
      cynomolgus monkeys were given daily po (capsule) doses of either 0, 3, 10, or 30
      (reduced to 20) mg/kg/day for 26 weeks. Two monkeys from each of the control and
      10 mg/kg/day dose groups were observed for 90 days after the last dose. Clinical
      observations, clinical chemistry, determination of key hormones, gross and
      microscopic pathology, cell proliferation, peroxisomal proliferation, bile-acid
      determination, and serum and liver perfluorooctanoate (PFOA) concentrations were
      monitored. Toxicity, including weight loss and reduced food consumption, was
      noted early in the study at the 30 mg/kg/day dose; therefore, the dose was
      reduced to 20 mg/kg/day. The same signs of toxicity developed in 3 monkeys at 20
      mg/kg/day, after which treatment of these monkeys was discontinued. One 30/20
      mg/kg/day monkey developed the signs of toxicity noted above and a possible
      dosing injury, and this monkey was sacrificed in extremis on Day 29. A 3
      mg/kg/day dose-group monkey was sacrificed in extremis on Day 137 for reasons not
      clearly related to APFO treatment. Dose-dependent increases in liver weight as a
      result of mitochondrial proliferation occurred in all APFO-treated groups.
      Histopathologic evidence of liver injury was not observed at either 3 or 10
      mg/kg/day. Evidence of liver damage was seen in the monkey sacrificed in moribund
      condition at the highest dose. Body weights were decreased at 30/20 mg/kg. PFOA
      concentrations in serum and liver were highly variable, were not linearly
      proportional to dose, and cleared to background levels within 90 days after the
      last dose. A no observable effect level was not established in this study, and
      the low dose of 3 mg/kg/day was considered the lowest observable effect level
      based on increased liver weight and uncertainty as to the etiology leading to the
      moribund sacrifice of one low-dose monkey on Day 137. Other than those noted
      above, there were no APFO-related macroscopic or microscopic changes, changes in
      clinical chemistry, hormones, or urinalysis, or hematological effects. In
      particular, effects that have been associated with the development of pancreatic
      and testicular toxicity in rats were not observed in this study.

PMID- 12215681
TI  - In vitro sub-hemolytic effects of butoxyacetic acid on human and rat
      erythrocytes.
AB  - When 2-butoxyethanol (2-BE) is administered to rats, hemolysis occurs as the
      active metabolite butoxyacetic acid (BAA) is formed. Human red blood cells appear
      to be relatively resistant to the hemolytic effects of BAA in vitro, whereas rat
      red blood cells undergo changes in deformability, cell swelling, and hemolysis.
      In this study, exposure of human red blood cells to high concentrations of BAA
      resulted in loss of deformability and a small increase in mean cellular volume,
      but no significant hemolysis. These changes resembled the changes that occur in
      rat erythrocytes exposed to much lower concentrations of BAA. Therefore, a
      comparison was made between the sub-hemolytic effects of BAA at high
      concentrations (up to 10 mM) on human red cells with the sub-hemolytic effects of
      lower concentrations of BAA (up to 0.1 mM) on rat erythrocytes. Under these
      conditions, human and rat erythrocyte deformability decreased, while mean
      cellular volume (MCV) and osmotic fragility increased. Although there was a
      substantial shift in rat erythrocytes to lower densities, human erythrocyte
      density was only slightly decreased. Human and rat erythrocyte sodium also
      increased. Rat erythrocytes demonstrated increased spherocytosis. In a survey of
      blood samples from adults and children, none demonstrated an increase in
      hemolysis (n = 97) or MCV (n = 65) after exposure to 10 mM BAA for 4 h. In these
      experiments, in which hemolysis was not evident, human erythrocytes required
      exposure to a 100-fold greater concentration of BAA to develop changes in red
      cell deformability, osmotic fragility, and sodium content similar to those
      observed in rat erythrocytes. These concentrations are not likely to occur under
      normal human use of 2-BE-containing products.

PMID- 12215682
TI  - The relative toxicity of substituted phenols reported in cigarette mainstream
      smoke.
AB  - Cigarette mainstream smoke (MS) contains a number of structurally diverse
      substituted phenols. Recent quantitative structure activity relationship (QSAR)
      studies on phenols show that substituted phenols with electron-releasing groups
      can form potentially toxic phenoxyl-free radicals. In contrast, substituted
      phenols with electron-withdrawing groups do not form phenoxyl-free radicals but
      exert their toxicity primarily through lipophilicity. The chemical structures of
      253 different substituted phenols reported in MS have been described in
      sufficient detail to allow identification of the individual compounds. From a
      laterally validated equation based on published data on the toxic effects of
      phenols on cultured cells, the relative toxicity, on a molar basis, of the 253 MS
      phenols has been determined. Based on this scheme, the most toxic phenols in MS
      include, in descending order of toxicity, 2-(dimethylamino)-phenol, 2-ethyl-6
      methyl-1,4-benzenediol, 2-methoxy-1,4-benzenediol, and 4-ethyl-2-methoxy-6
      methylphenol. The least toxic phenols include, in ascending order of toxicity, 4
      hydroxybenzoic acid and 3-hydroxybenzenepropanoic acid. In the human exposure
      situation, the toxicity of MS phenols is a complex interaction, with
      contributions made by the following factors: toxicity per mole; MS concentration;
      synergistic, additive or antagonistic interactions with other MS components; host
      susceptibility; metabolism; and individual smoking behavior and inhalation
      patterns. In the absence of data to the contrary, reduction in the number and
      concentration of toxic MS smoke components may be considered to be advantageous.
      Studies of this type can play an important role in identifying MS components for
      reduction or removal.

PMID- 12215683
TI  - Nuclear and nucleolar glutathione reductase, peroxidase, and transferase
      activities in livers of male and female Fischer-344 rats.
AB  - The present studies were to test the hypotheses that glutathione reductase (GR),
      glutathione peroxidase (GPX), and glutathione S-transferase (GST) activities are
      expressed in nuclei and nucleoli of rat liver cells, and that differences in
      activities of these enzymes would correlate with the greater resistance of female
      than of male Fischer-344 rats to hepatic necrosis in vivo, mediated by reactive
      oxygen species generated by redox-cycling metabolism of diquat. Adult male and
      female Fischer-344 rats were treated with comparably hepatotoxic doses of diquat
      (0.1 or 0.2 mmol/kg, respectively), or equal volumes of saline, ip. Six hours
      later, the livers were harvested, and purified nuclei and nucleoli were isolated
      by differential centrifugation. Nuclear GR activities in male and female rats
      were 12 and 15 mU/mg protein, and nucleolar activities were 30 and 51 mU/mg
      protein, respectively, p < 0.05. Some differences between male and female rats in
      nuclear and nucleolar activities of GPXs and GSTs were observed, as were some
      differences in the respective diquat-treated animals, but implications of these
      differences for susceptibility to diquat-induced oxidant stress effects are not
      apparent. Nuclear GR, GPX, and GST probably contribute to antioxidant defense
      mechanisms, but the functions served by localization of GR and GPX in nucleoli
      are less evident.

PMID- 12215684
TI  - "Effects of subchronic exposure to a complex mixture of persistent contaminants
      in male rats: systemic, immune and reproductive effects".

PMID- 12215686
TI  - Do all projects require ethics committee clearance?

PMID- 12215688
TI  - Effect of St. John's Wort extract on intestinal expression of cytochrome P4501A2:
      studies in LS180 cells.
AB  - BACKGROUND AND AIMS: St. John's Wort (SJW) is known to induce expression and
      activity of cytochrome P4503A4 (CYP3A4). However, its effects on other cytochrome
      P450 (CYP) are not well understood. Our objective was to characterise the effect
      of SJW on the expression of CYP1A2 in the LS180 intestinal cell model. STUDY
      DESIGN AND METHODS: LS180 cells were cultured in the presence and absence of SJW
      extract for 48 hours. CYP1A2 protein content was measured by Western blot
      analysis using monoclonal antibody. Time-dependent expression of CYP1A2 was
      assessed during exposure to SJW extract for 24 hours and following its removal
      for another 24 hours. RESULTS: SJW increased the expression of CYP1A2 in the
      LS180 cells in a concentration dependent manner. The induction was time
      dependent, as enzyme levels returned to baseline within 4-8 hours after removal
      of SJW. CONCLUSIONS: SJW reversibly induces expression of CYP1A2 in LS180 cells.
      This induction may be responsible for reduced plasma theophylline concentrations
      upon co-administration of SJW, as reported earlier.

PMID- 12215687
TI  - Cumulative effect of risk factors on short-term surgical success of mitomycin
      augmented trabeculectomy.
AB  - CONTEXT: Risk factors for failure of trabeculectomy may have a cumulative effect
      on the outcome. AIMS: To study the effect of preoperative ocular risk factors on
      the surgical outcome of trabeculectomy augmented with 2 commonly used doses of
      Mitomycin C. SETTINGS AND DESIGN: In a prospective cohort study, cases were
      recruited over an 18 month period. 92 eyes of 83 patients with one to three known
      risk factors for failure of trabeculectomy underwent Mitomycin-C (MMC) augmented
      trabeculectomy. METHODS AND MATERIAL: Trabeculectomy was done with a randomly
      chosen MMC dose of 0.2 mg/ml or 0.4 mg/ml. All cases were followed up for a
      period of at least 3 months. Surgical success was defined as the lowering of
      intraocular pressure (IOP) below 21 mmHg during the follow up period. STATISTICAL
      ANALYSIS USED: Chi square test, paired t test, odds ratio, effect size. RESULTS:
      Eyes with two or three risk factors (out of aphakic glaucoma, failed
      trabeculectomy, neovascular glaucoma, post uveitic glaucoma, traumatic glaucoma,
      adherent leucoma, juvenile glaucoma, prolonged medical therapy, steroid induced
      glaucoma, post penetrating keratoplasty glaucoma and developmental glaucoma) had
      a significantly poorer surgical success rate (88% and 78%) than eyes with one
      risk factor (100%). 0.4 mg/ml MMC used sub-sclerally had a statistically similar
      effect on lowering the IOP as 0.2 mg/ml in all groups. The rate of complications
      was significantly higher in the 0.4 mg/ml subgroup. CONCLUSIONS: The presence of
      more than one preoperative ocular risk factor, affects the surgical success of
      MMC augmented trabeculectomy in high-risk cases. Because of the significantly
      higher rate of complications with the higher dose of MMC, this should be used
      sparingly, only in cases with more than two risk factors.

PMID- 12215689
TI  - Predictors of nocturnal oxygen desaturation in chronic obstructive pulmonary
      disease in a South Indian population.
AB  - CONTEXT: Nocturnal Oxygen Desaturation (NOD) in patients with chronic obstructive
      pulmonary disease (COPD) is associated with a poor prognosis. AIMS: To document
      the occurrence of NOD in COPD and to identify factors which might predict NOD in
      COPD patients with daytime arterial oxygen tension (PaO2) > or =60 mm Hg.
      SETTINGS AND DESIGN: This prospective study was conducted in patients attending
      the special respiratory clinics or admitted in JIPMER, Pondicherry. METHODS AND
      MATERIAL: Thirty consecutive patients with COPD were divided into two groups,
      desaturators and non-desaturators on the basis of nocturnal oxygen saturation.
      STATISTICAL ANALYSIS USED: Unpaired 't' test, Karl Pearson's correlation equation
      and stepwise multiple regression analysis was done. RESULTS: Fourteen patients
      (46.6%) experienced NOD. Desaturators had lower awake oxygen saturation, PaO2,
      forced vital capacity, forced expiratory volume in one second and peak expiratory
      flow rate. There was positive correlation between nocturnal O2 saturation and
      PaO2 (r=0.638 and P value =0.014) and awake SPO2 (r=0.901 and P value <0.001).
      CONCLUSIONS: The rate of occurrence of NOD in COPD was 46.6%. Awake SPO2 is the
      only single predictor of nocturnal oxygen desaturation in these patients.

PMID- 12215690
TI  - Patient-led partner referral in a district hospital based STD clinic.
AB  - CONTEXT: Sexual communication and appropriate treatment of sexual partners is
      critical to the success of STD and HIV/AIDS prevention and control. AIMS: To
      understand factors influencing intention of STD patients to inform their regular
      sexual partners and identify predictors influencing actual return of the
      partners. SETTINGS AND DESIGN: A non-randomised survey of patients attending STD
      clinic in a district hospital between May and November 2000. METHODS AND
      MATERIAL: 182 patients were administered structured questionnaires to understand
      their intention to notify their regular sexual partners and encouraged to refer
      their regular sexual partners to the clinic for management. Factors related to
      intent to notify partners and actual partner referral were analysed. STATISTICAL
      ANALYSIS USED: Chi square test and forward stepwise logistic regression. RESULTS:
      Of the 182 STD patients 77.47% expressed their positive intention to notify their
      regular sexual partners. However, overall partner return rate was 40.65%.
      Patients from a better economic class (p=0.014), those who had sex since having
      the disease (p=0.001), those who felt it was easy to tell their partners
      (p=0.047) and perceived the necessity of investigating their partners (p<0.001)
      were more likely to have an intention to notify their partners. Independent
      predictors of actual return of sexual partners were patients' perception of
      partners' susceptibility (p=0.044), positive intention to notify partners
      (p=0.001), partners already informed before clinic visit (p=0.030) and presence
      of genital ulcerative diseases (p=0.033). CONCLUSIONS: STD clinic counselling and
      education should focus on risk reduction, partner susceptibility, role of STDs in
      HIV transmission and improving spousal communication.

PMID- 12215691
TI  - Efficacy of intravenous ketoprofen for pre-emptive analgesia.
AB  - AIM: To determine whether intravenous ketoprofen is effective as pre-emptive
      analgesia for breast surgery. DESIGN: Randomised, controlled, double blind study.
      PATIENTS AND METHODS: 50 patients undergoing breast surgery under general
      anaesthesia randomised to receive either 100 mg intravenous ketoprofen 30 minutes
      before (Group I), or immediately after surgical incision (Group II).
      Postoperatively, pain scores (Visual Analogue Scale, VAS) and time to rescue
      analgesic were recorded by an independent, blinded observer. The study was
      terminated when rescue analgesic was required (VAS > or =4 or demand for
      analgesic). STATISTICAL ANALYSIS: Continuous variables were analysed by the
      unpaired 't' test, discrete variables with the chi square test, and survival
      curves by the log-rank test. RESULTS: Pain scores were significantly lower in
      Group I till 10 hours after surgery. The number of patients requiring analgesia
      at 4, 6, 8 and 10 hours was significantly lower in group I (0% vs. 47% [P
      <0.0001], 0% vs. 44% [P <0.003], 0% vs. 80% [P <0.0001], 0% vs. 100% [P <0.0001]
      respectively). The mean time for rescue analgesic was 15.47 -/+ 2.87 hours in
      group I versus 4.22 -/+ 2.55 hours in group II (P <0.0001). CONCLUSION: Pre
      emptive analgesia with Intravenous ketoprofen (100mg) produces better
      postoperative pain-relief in patients undergoing breast surgery.

PMID- 12215692
TI  - Correlation of fine needle aspiration cytology, smear and culture in tuberculous
      lymphadenitis: a prospective study.
AB  - BACKGROUND AND AIM: Bacteriological studies are necessary to confirm the
      diagnosis of tuberculous lymphadenitis, as cytological appearances mimic other
      granulomatous lesions. The objective was to assess the diagnostic role of culture
      of fine needle aspiration done on clinically suspected cases of tuberculous
      lymphadenitis and to determine the prevalence of drug resistance in M.
      tuberculosis isolates. SETTING AND DESIGN: A prospective, double-blind study over
      a period of one year in a tertiary care hospital. MATERIAL AND METHODS: Fine
      needle aspiration cytology and culture were done on 250 patients with clinical
      suspicion of tuberculous lymphadenitis. STATISTICAL ANALYSIS: Data was
      statistically analysed using chi square test. Sensitivity, specificity, positive
      predictive and negative predictive values and likelihood ratio were also
      calculated. RESULT: Of the 161 cytologically or microbiologically proven cases of
      tuberculous lymphadenitis, cytological changes consistent with tuberculosis were
      observed in 133 patients, out of which mycobacteria were isolated in 102
      aspirates. Mycobacteria were also isolated from 28 aspirates cytologically missed
      as tuberculous lymphadenitis. Of the 130-mycobacterial isolates, 5 were non
      tuberculous mycobacteria. Culture positivity was significantly higher (P<0.001)
      than smear positivity. Drug susceptibility studies showed resistance to one or
      more drugs in 61% of isolated strains with maximum resistance to isoniazid (16%
      primary and 48% secondary) and minimum to ethambutol (4% primary and 12%
      secondary). CONCLUSION: Culture for mycobacteria should be carried out on all
      aspirates from patients suspected with tuberculous lymphadenitis.

PMID- 12215693
TI  - Clinical profile of leptospirosis in South gujarat.
AB  - BACKGROUND: South Gujarat has been witnessing increasing incidence of
      leptospirosis for the last few years. AIM: To study the clinical profile of
      leptospirosis in South Gujarat. SETTINGS AND DESIGN: Prospective study during
      July-September 2000 at the New Civil Hospital, Surat, Gujarat. PATIENTS AND
      METHODS: All the consecutive cases with clinical suspicion of leptospirosis were
      screened for lgM antileptospira antibody on the first and the fourteenth day. A
      four fold or greater increase in agglutinin antibody titre on paired samples was
      considered diagnostic. If the patient died before the fourteenth day then initial
      titre greater than 1:15 was considered diagnostic. RESULTS: Total number of
      patients referred to the hospital were fifty, of which thirty-eight [33 males,
      with age 14-50 (30 +/- 10.51)] were diagnosed as having leptospirosis. Most
      common organs involved were liver (27, 71.05%) and kidney (24, 63.15%). Cardio
      vascular (12, 31.5%), pulmonary (10, 26.35%), neurological (2, 5.26%) and
      haematological (8, 21%) involvements were less common. Six patients died because
      of pulmonary involvement in the form of alveolar haemorrhage, while one died
      because of cardiac involvement. CONCLUSION: Liver and kidney were the most
      commonly involved organs in severe leptospirosis. Pulmonary involvement, though
      uncommon, led to high mortality.

PMID- 12215695
TI  - Large bilateral star-shaped calculi in the seminal vesicles.
AB  - Calculi in the seminal vesicles (SV) are extremely rare. A patient having large
      bilateral star-shaped calculi in the SV is reported. They were seen on plain x
      ray and confirmed by computed tomography. On the reconstructed CT scans the large
      stone on the right side measured about 35 X 35 X 50 mm and the one on the left,
      30 X 20 X 45 mm. They were not felt on rectal examination, as they were situated
      laterally.

PMID- 12215694
TI  - Cavernous sinus syndrome as the only manifestation of sarcoidosis.
AB  - We describe a 63-year-old Afro-Caribbean female who presented with complete
      ophthalmoplegia of the right eye. Magnetic resonance imaging revealed a mass in
      the cavernous sinus, which was pathologically confirmed as due to sarcoidosis. No
      clinical or laboratory evidence of sarcoidosis was found in any other organs. We
      believe this is the first reported case of an isolated cavernous sinus syndrome
      due to sarcoidosis and suggest that sarcoidosis should be considered in the
      differential diagnosis of cavernous sinus syndromes even in the absence of
      systemic involvement of sarcoidosis.

PMID- 12215696
TI  - Burkholderia pseudomallei: abscess in an unusual site.
AB  - Melioidosis is an infection caused by Burkholderia pseudomallei. It is an
      important human pathogen in tropical area. The clinical manifestations are
      protean and multisystem involvement. We report an unusual case of melioidosis
      with abscess at root of mesentery in an elderly, non-insulin dependent diabetic
      Thai women. She presented with prolonged fever and chronic abdominal pain. The
      early clinical diagnosis was carcinomatous mass with peritonitis. Diagnosis of
      melioidosis arose from the surgical finding and pus culture. Treatment with
      surgical drainage and ceftazidime followed by co-trimoxazole plus doxycycline had
      a good clinical outcome.

PMID- 12215697
TI  - Coexisting chondroblastoma and osteochondroma: a case report.
AB  - The coexistence of two different types of benign cartilaginous tumours of bone in
      the same patient has not been reported in literature. We report a case in which a
      sixteen-year-old male had a benign chondroblastoma of the proximal left humerus
      and an osteochondroma of the distal left femur. Both originated at the same time
      and had a progressive increase in size with growth.

PMID- 12215698
TI  - Fryns syndrome.

PMID- 12215699
TI  - Leptospirosis associated with diffuse alveolar haemorrhage.

PMID- 12215700
TI  - Foetus in fetu.

PMID- 12215701
TI  - Pulmonary sarcoidosis: management.
AB  - During the last two decades many advances have been made in the field of
      sarcoidosis. The disease is now recognised as a multisystem disorder occurring in
      patients with a genetic predisposition and an exposure to yet unknown
      transmissible environmental agent/s. The diagnosis is based on a compatible
      clinical and/or radiological picture, histological evidence of non-caseating
      granuloma and exclusion of other diseases capable of producing a similar clinical
      or histological picture. Treatment primarily consists of administration of
      corticosteroids, although there are valuable alternative drugs. Treatment should
      be considered in symptomatic patients with evidence of radiologic or lung
      function deterioration. The patients with extra-pulmonary involvement
      particularly with ocular, myocardial, and neuro-sarcoidosis almost always need
      treatment. For asymptomatic pulmonary sarcoidosis patients no therapy is needed.

PMID- 12215702
TI  - Bone graft substitutes: past, present, future.
AB  - Bone grafts are necessary to provide support, fill voids, and enhance biologic
      repair of skeletal defects. They are used by orthopaedic surgeons, neurosurgeons,
      craniofacial surgeons, and periodontists. Bone harvested from donor sites is the
      gold standard for this procedure. It is well documented that there are
      limitations and complications from the use of autograft, including the limited
      quantity and associated chronic donor site pain. Despite the increase in the
      number of procedures that require bone grafts, there has not been a single ideal
      bone graft substitute Scientists, surgeons, and medical companies, thus, have a
      tremendous responsibility to develop biologic alternatives that will enhance the
      functional capabilities of the bone graft substitute, and potentially reduce or
      eliminate the need for autograft. This article is an attempt to review the past
      and existing bone graft substitutes, and future directions of research. The
      historical data was extracted after thorough review of the literature. The data
      for the current concepts and future directions was compiled from the Internet,
      and from direct correspondence with medical companies. Since many products are
      undergoing clinical trials, and are yet not commercially available, their data
      cannot be found in literature. The main purpose of this article is to give the
      reader an idea about the existing market products and products likely to be
      available in near future.

PMID- 12215703
TI  - Genetics of gallstone disease.
AB  - Gallstone disease is a complex disorder where both environmental and genetic
      factors contribute towards susceptibility to the disease. Epidemiological and
      family studies suggest a strong genetic component in the causation of this
      disease. Several genetically derived phenotypes in the population are responsible
      for variations in lipoprotein types, which in turn affect the amount of
      cholesterol available in the gall bladder. The genetic polymorphisms in various
      genes for apo E, apo B, apo A1, LDL receptor, cholesteryl ester transfer and LDL
      receptor-associated protein have been implicated in gallstone formation. However,
      presently available information on genetic differences is not able to account for
      a large number of gallstone patients. The molecular studies in the animal models
      have not only confirmed the present paradigm of gallstone formation but also
      helped in identification of novel genes in humans, which might play an important
      role in pathogenesis of the disease. Precise understanding of such genes and
      their molecular mechanisms may provide the basis of new targets for rational drug
      designs and dietary interventions.

PMID- 12215704
TI  - Tumour induced hydrocephalus and oedema: pathology or natural defence.

PMID- 12215705
TI  - Doctor bashing and why the Indian medical profession must evolve.

PMID- 12215706
TI  - Fever of unknown origin in internal medicine.

PMID- 12215707
TI  - Advancing laparoscopic surgery in urology.

PMID- 12215708
TI  - Codman's triangle in tubercular osteomyelitis.

PMID- 12215709
TI  - Intracranial bleeding in Weil's disease.

PMID- 12215710
TI  - Transient cerebellar mutism after posterior fossa surgery.

PMID- 12215711
TI  - History of dermatology, venereology and leprology in India.

PMID- 12215713
TI  - Molecular mechanisms and cellular biology of the steroid receptor coactivator
      (SRC) family in steroid receptor function.

PMID- 12215712
TI  - The normal human menstrual cycle.

PMID- 12215714
TI  - Estrogen receptors: structure, mechanisms and function.

PMID- 12215715
TI  - Progesterone regulation of reproductive function through functionally distinct
      progesterone receptor isoforms.

PMID- 12215716
TI  - Pharmacokinetics and potency of progestins used for hormone replacement therapy
      and contraception.

PMID- 12215717
TI  - Estrogens.

PMID- 12215718
TI  - Selective estrogen receptor modulators.

PMID- 12215719
TI  - Hormonal replacement therapy.

PMID- 12215720
TI  - Recent developments in hormonal contraception.

PMID- 12215721
TI  - Proven and potential clinical applications of mifpristone (RU486).

PMID- 12215722
TI  - Noncontraceptive health benefits of oral contraceptives.

PMID- 12215723
TI  - A unified mechanism for spontaneous-rate and first-spike timing in the auditory
      nerve.
AB  - Recent physiological experiments have provided detailed descriptions of the
      properties of first-spike latency and variability in auditory cortex and nerve in
      response to pure tones with different envelopes. The envelope-dependence of first
      spike timing and precision in auditory cortical neurons appears to reflect
      properties established in the nerve. First-spike latency properties in individual
      auditory nerve fibers are strongly correlated with their spontaneous rate (SR).
      It is shown here that a minimal, plausible model of auditory transduction with
      two free parameters accurately reproduces the physiological data from the
      auditory nerve population. The model consists of a simple gain stage, a bandpass
      filter, a rectifying saturating non-linearity, and a lowpass filter in series.
      The output of the lowpass filter drives an inhomogeneous Poisson process. The
      shape of the non-linearity is determined by SR; in physiological terms, this
      shape depends upon the resting sensitivity of the synapse between the inner hair
      cell and the auditory nerve. An alternative model for SR generation, where SR is
      added to the stimulus-driven output of a fixed nonlinearity, fails to account for
      the data. The results provide a novel, comprehensive and physiologically-based
      explanation for the range of experimental results on the envelope-dependence of
      first-spike latency and precision, and its relationship with SR, in the auditory
      system.

PMID- 12215724
TI  - States of high conductance in a large-scale model of the visual cortex.
AB  - This paper reports on the consequences of large, activity dependent, synaptic
      conductances for neurons in a large-scale neuronal network model of the input
      layer 4Calpha of the Macaque primary visual cortex (Area V1). This high
      conductance state accounts for experimental observations about orientation
      selectivity, dynamics, and response magnitude (D. McLaughlin et al. (2000) Proc.
      Natl. Acad. Sci. USA 97: 8087-8092), and the linear dependence of Simple cells on
      visual stimuli (J. Wielaard et al. (2001) J. Neuroscience 21: 5203-5211). The
      source of large conductances in the model can be traced to inhibitory
      corticocortical synapses, and the model's predictions of large conductance
      changes are consistent with recent intracellular measurements (L. Borg-Graham et
      al. (1998) Nature 393: 369-373; J. Hirsch et al. (1998) J. Neuroscience 15: 9517
      9528; J.S. Anderson et al. (2000) J. Neurophysiol. 84: 909-926). During visual
      stimulation, these conductances are large enough that their associated time
      scales become the shortest in the model cortex, even below that of synaptic
      interactions. One consequence of this activity driven separation of time-scales
      is that a neuron responds very quickly to temporal changes in its synaptic drive,
      with its intracellular membrane potential tracking closely an effective reversal
      potential composed of the instantaneous synaptic inputs. From the effective
      potential and large synaptic conductance, the spiking activity of a cell can be
      expressed in an interesting and simplified manner, with the result suggesting how
      accurate and smoothly graded responses are achieved in the model network.
      Further, since neurons in this high-conductance state respond quickly, they are
      also good candidates as coincidence detectors and burst transmitters.

PMID- 12215725
TI  - Computation by ensemble synchronization in recurrent networks with synaptic
      depression.
AB  - While computation by ensemble synchronization is considered to be a robust and
      efficient way for information processing in the cortex (C. Von der Malsburg and
      W. Schneider (1986) Biol. Cybern. 54: 29-40; W. Singer (1994) Inter. Rev. Neuro.
      37: 153-183; J.J. Hopfield (1995) Nature 376: 33-36; E. Vaadia et al. (1995)
      Nature 373: 515-518), the neuronal mechanisms that might be used to achieve it
      are yet to be uncovered. Here we analyze a neural network model in which the
      computations are performed by near coincident firing of neurons in response to
      external inputs. This near coincident firing is enabled by activity dependent
      depression of inter-neuron connections. We analyze the network behavior by using
      a mean-field approximation, which allows predicting the network response to
      various inputs. We demonstrate that the network is very sensitive to temporal
      aspects of the inputs. In particular, periodically applied inputs of increasing
      frequency result in different response profiles. Moreover, applying combinations
      of different stimuli lead to a complex response, which cannot be easily predicted
      from responses to individual components. These results demonstrate that networks
      with synaptic depression can perform complex computations on time-dependent
      inputs utilizing the ability to generate temporally synchronous firing of single
      neurons.

PMID- 12215726
TI  - Auditory temporal computation: interval selectivity based on post-inhibitory
      rebound.
AB  - The measurement of time is fundamental to the perception of complex, temporally
      structured acoustic signals such as speech and music, yet the mechanisms of
      temporal sensitivity in the auditory system remain largely unknown. Recently,
      temporal feature detectors have been discovered in several vertebrate auditory
      systems. For example, midbrain neurons in the fish Pollimyrus are activated by
      specific rhythms contained in the simple sounds they use for communication. This
      poses the significant challenge of uncovering the neuro-computational mechanisms
      that underlie temporal feature detection. Here we describe a model network that
      responds selectively to temporal features of communication sounds, yielding
      temporal selectivity in output neurons that matches the selectivity functions
      found in the auditory system of Pollimyrus. The output of the network depends
      upon the timing of excitatory and inhibitory input and post-inhibitory rebound
      excitation. Interval tuning is achieved in a behaviorally relevant range (10 to
      40 ms) using a biologically constrained model, providing a simple mechanism that
      is suitable for the neural extraction of the relatively long duration temporal
      cues (i.e. tens to hundreds of ms) that are important in animal communication and
      human speech.

PMID- 12215727
TI  - Modelling inter-segmental coordination of neuronal oscillators: synaptic
      mechanisms for uni-directional coupling during swimming in Xenopus tadpoles.
AB  - Locomotion requires longitudinal co-ordination. We have examined uni-directional
      synaptic coupling processes between two classes of neuronal network oscillators:
      autonomously active "intrinsic" oscillators, and "potential" oscillators that
      lack sufficient excitatory drive for autonomous activity. We model such
      oscillator networks in the bilaterally-symmetrical, Xenopus tadpole spinal cord
      circuits that co-ordinate swimming. "Glutamate" coupling EPSPs can entrain a
      second oscillator of lower frequency provided their strength is sufficient. Fast
      (AMPA) EPSPs advance spiking on each cycle, while slow (NMDA) EPSPs increase
      frequency over many cycles. EPSPs can also enable rhythmicity in "potential"
      oscillators and entrain them. IPSPs operate primarily on a cycle-by-cycle basis.
      They can advance or delay spiking to entrain a second "intrinsic" oscillator with
      higher, equal or lower frequency. Bilaterally symmetrical coupling connections
      operate twice per cycle: once in each half-cycle, on each side of the receiving
      oscillator. Excitatory and inhibitory coupling allow entrainment in complimentary
      areas of parameter space.

PMID- 12215728
TI  - Prevalence and incidence of arrhythmias and sudden death in heart failure.
AB  - Patients with heart failure are prone to a variety of arrhythmias, symptomatic
      and asymptomatic, that are prognostically significant and have an important
      bearing on the management of these patients. However there are some inherent
      problems in assessing the frequency of these arrhythmias within a large patient
      population, due to a lack of uniformity in defining heart failure and the
      transient nature of these rhythms. Patients with heart failure commonly die
      suddenly. The causes of these deaths are difficult to ascertain accurately and
      are often presumed arrhythmic. With the advent of effective interventions to
      prevent sudden death, accurately defining the causal relationship between the
      arrhythmias and sudden death has assumed great importance to appropriately target
      therapy. Several attempts have been made to predict such deaths on the basis of
      non-invasive and invasive diagnostic investigations with variable success. In
      this article we review the incidence and prevalence of atrial and ventricular
      arrhythmias and sudden deaths in epidemiological studies, surveys and randomised
      control trials of patients with heart failure. We discuss the prognostic
      significance of these arrhythmias, the inherent problems in their diagnosis and
      whether their presence predicts the risk of sudden deaths and the mode of such
      deaths in the heart failure population. The role of various investigations in
      risk stratification of sudden death has also been discussed.

PMID- 12215730
TI  - Sudden death in heart failure: underlying electrophysiological mechanisms.

PMID- 12215729
TI  - Mechanisms underlying the development of atrial arrhythmias in heart failure.
AB  - There is an important association between heart failure and the development of
      atrial arrhythmias. Although most often associated with atrial fibrillation,
      there is some evidence to suggest an association between heart failure and other
      atrial arrhythmias and, in particular, atrial flutter and atrial tachycardia. The
      mechanisms by which these common atrial arrhythmias may arise in patients with
      heart failure are discussed.

PMID- 12215731
TI  - Anti-thrombotic strategies for patients with atrial fibrillation and heart
      failure.
AB  - Atrial fibrillation occurs commonly in the setting of congestive heart failure
      and, in fact can cause left ventricular dysfunction due to a rapid ventricular
      response over time, termed tachycardia-mediated cardiomyopathy. The combination
      of atrial fibrillation and congestive heart failure leads to a high risk of
      stroke for the patient and appropriate antithrombotic therapy can minimize this
      incidence of stroke. Stroke risk can be markedly reduced by treatment with
      warfarin and complications of anticoagulation minimized by close attention to
      maintaining the INR between 2.0 and 3.0.

PMID- 12215732
TI  - Prevention of and medical therapy for atrial arrhythmias in heart failure.
AB  - A large proportion of heart failure patients suffer from atrial arrhythmias,
      prime amongst them being atrial fibrillation (AF). Ventricular dysfunction and
      the syndrome of heart failure can also be a concomitant pathology in up to 50% of
      patients with AF. However this association is more than just due to shared risk
      factors, research from animal and human studies suggest a causal relationship
      between AF and heart failure. There are numerous reports of tachycardia-induced
      heart failure where uncontrolled ventricular rate in AF results in heart failure,
      which is reversible with cardioversion to sinus rhythm or ventricular rate
      control. However the relationship extends beyond tachycardia-induced
      cardiomyopathy. Optimal treatment of AF may delay progressive ventricular
      dysfunction and the onset of heart failure whilst improved management of heart
      failure can prevent AF or improve ventricular rate control. Prevention and
      treatment of atrial arrhythmias, and in particular atrial fibrillation, is
      therefore an important aspect of the management of patients with heart failure.
      This review describes the incidence and possible predictors of AF and other
      atrial arrhythmias in patients with heart failure and discusses the feasibility
      of primary prevention. The evidence for the management of atrial fibrillation in
      heart failure is systematically reviewed and the strategies of rate versus rhythm
      control discussed in light of the prevailing evidence.

PMID- 12215735
TI  - [HANDLING OF VARICOSE HEMORRHAGE IN CIRRHOTIC PATIENT]

PMID- 12215733
TI  - Significance and control of cardiac arrhythmias in patients with congestive
      cardiac failure.
AB  - A wide spectrum of ventricular and supraventricular tachyarrhythmias occurs in
      the setting of congestive cardiac failure. However, the two most clinically
      significant are atrial fibrillation and ventricular tachycardia and fibrillation.
      In the past there has been much emphasis on premature ventricular contractions
      and more recently, on nonsustained ventricular tachycardia. For the most part,
      these arrhythmias are asymptomatic in heart failure. They are markers of sudden
      arrhythmic death but their suppression by antiarrhythmic drugs have not resulted
      in a reduction of total mortality. Two approaches have been used to this end. The
      first is the use of beta-adrenergic blocking drugs and antiarrhythmic agents such
      as amiodarone. Beta-blockers have been shown to significantly reduce sudden death
      as well as total mortality, while the effects of amiodarone have been less
      decisive. The prospective role of the implantable cardioverter defibrillator
      (ICD) is undergoing critical evaluation in patients with cardiac failure at high
      risk for sudden death. The elective role of the ICD is well established as first
      line therapy in patients with heart failure resuscitated from sudden death and in
      those with sustained ventricular tachycardia in conjunction with conventional
      therapies for cardiac decompensation. The prevalence of atrial fibrillation rises
      as a function of severity of cardiac failure, but it is also in known that
      persistent atrial fibrillation with an uncontrolled ventricular response may
      induce heart failure. Controlled ventricular response may prevent congestive
      heart failure and improve left ventricular function. The two most common causes
      of atrial fibrillation in cardiac failure in Europe and America are ischemic
      heart disease and hypertension, while mitral valve disease remains the prevalent
      cause elsewhere. The choice of antiarrhythmic drugs for maintaining sinus rhythm
      is critical in the prevention of heart failure aggravation and proarrhythmic
      reactions of antiarrhythmic drugs. Amiodarone and dofetilide are most widely used
      in this context.

PMID- 12215734
TI  - Devices for the management of ventricular arrhythmias in cardiac failure.
AB  - Heart failure is a common clinical syndrome with a high morbidity and mortality.
      Despite advances in medical treatment, death from dangerous ventricular
      arrhythmias is frequently implicated. Emerging evidence supports the use of the
      implantable cardioverter defibrillator for selected patients. This includes
      secondary prevention indications for patients who have survived life-threatening
      ventricular arrhythmias. In addition, patients who have not suffered spontaneous
      sustained ventricular arrhythmias, but who are at high risk for sudden arrhythmic
      death are starting to be recognized as candidates for ICD therapy. At present the
      only primary prevention indication with a good evidence base is the presence of
      inducible ventricular arrhythmias at electrophysiologic testing in patients with
      prior myocardial infarction, impaired left ventricular systolic function and non
      sustained ventricular tachycardia on Holter monitoring. Studies planned or in
      progress are likely to expand further the role of device therapy in the treatment
      of patients with cardiac failure.

PMID- 12215736
TI  - [SURGICAL TREATMENT OF POSTOPERATORY GASTROINTESTINAL FISTULAS]
AB  - A prospective 10-year protocol is reported. Twenty-eight patients were operated
      from postoperatory intercutaneous fistulas by the same surgeon. They were treated
      at a Surgical Referral Unit of Artificial Nutritional Support (SNA), acronym in
      Spanish from 284 patients with similar fistulas. Survival was of 85.7 per cent
      (24/28). A 92.9 per cent of patients (26/28) required SNA either enteral and/or
      parenteral. Three major aspects should be considered: First, the vital importance
      on an Artificial Nutritional Support team in order to attain nutritional
      repletion with the lowest possible morbimortality derived from a Phamacological
      Nutritional Support. Second, should surgical treatment be unsuccessful, multiple
      organ failure is the main cause of mortality. Third, surgical decision making
      shoul be based on established protocols.An adequate SNA is of major importance to
      avoid or decrease morbimortality derived from postoperatory fistulas, and at the
      same time, it is the cornerstone to resolve this complication surgically.

PMID- 12215737
TI  - [ENCAPSULATED CORD METHOD(Enterotest) COMPARED WITH FECALTEST ON THE DIAGNOSIS OF
      CRIPTOSPORIUM Sp E ISOSPORA belli In HIV(+)Patients with Gastrointestinal
      Symptoms]
AB  - Fecal samples and small intestinal content obtained by Enterotest were submitted
      between December 1994 and January 1996, by HIV (+) patients with gastrointestinal
      symptoms.Unconcentrated and concentrated fecal samples (by Sheater, Ritchie and
      Spontaneous Sedimentation) and intestinal content obtained by Enterotest, all
      stained by modificated Ziehl-Nielsen method, were compared (multiatributive
      comparison) based on the following parameters: yield, each test cost, morphology
      and the number of parasites per slide, in order to diagnose Cryptosporidium spp.
      e Isospora belli.Intestinal content obtained by Enterotest on the diagnosis of
      Cryptosporidium spp. e Isospora belli was not better than the fecal samples but
      it is more expensive. However, it reached a good diagnostic yield with adequate
      morphology, and a number of parasites per slide. Furthermore, it can be used as a
      second line diagnostic method (first line = fecal samples) and as an alternative
      in places where the use of endoscopy is not available.

PMID- 12215738
TI  - [DIAGNOSIS AND TREATMENT OF CYCLOSPORA CAYETANENSISINFECTION IN PAEDIATRIC
      PATIENTS]
AB  - The study was made to determine the clinical profile and laboratory of 10
      paediatric patients whose diagnosis of cyclosporiosis was established by
      identifying the parasite in fecal matter, through a smear with modified Zehl
      Nielsen and incubation in dichromate of potassium. We obtained clinical data form
      these patients correlating them with absorption tests (digestive activity, sugar
      reducers and fats in feces.)After treatment with trimethroprim-sulfamethoxazole
      and nitazoxanide patients were controlled by laboratory exams to determine the
      existence of the parasite and its viability.

PMID- 12215739
TI  - [PORTAL HYPERTENSIVE GASTROPATHY AT HOSPITAL NACIONAL DELSUR - IPSS AREQUIPA]
AB  - An analytic prospective study was done in cirrhotic patients with Portal
      hypertension to study a new pathology known as Portal Hypertensive Gastropathy.
      In 73.3 per cent of patients with cirrhosis, hospitalized inthe Gastroenterology
      Area, Portal Hypertensive Gastropathy was present. Males in the 4th decade of
      their life were predominant. Mild gastropathy with a mosaic or snake skin
      endoscopy pattern was the most frequent (60.6%), while in severe gastropathy, the
      most common pattern was cherry red spots. These lesions were often located in the
      stomach fundus and body. All the patients presented some vascular alteration and
      lymphoplasmocytic inflammatory infiltration. No relation was found between the
      severity of Portal Hypertension or Advanced Liver Disease and changes of the
      gastric mucosa.

PMID- 12215740
TI  - [ASSOCIATION OF DUODENAL DIVERTICULUM PRESENCE WITH CHOLEDOCHOLITHIASIS]
AB  - OBJECTIVES: The aim of this study was to investigate in aretrospective way the
      frequency of duodenal diverticulum and its association with choledocholithiasis.
      Methods:This study included 2728 consecutive patients who underwent ERCP during
      the period 1993-1997. Duodenal diverticulum was discovered in 122 cases (4.5%).
      In 22 patients cannulation was not achieved since it was not technically
      possible. Results: In 100 patients with successful cannulation, 54 cases with
      juxtapapillary diverticulum were encountered associated with choledocholithiasis.
      CONCLUSION: These data suggestthat duodenal diverticulum is associated with
      choledocholithiasis.

PMID- 12215741
TI  - [ASCITES IN HEPATIC CIRRHOSIS: RECOGNITION INVESTIGATIONAND TREATMENT]
AB  - Hepatic cirrhosis is the most common cause of ascites. It is caused by liver
      failure leading to complex interrelated circulatory and renal changes resulting
      in retention of sodium and water and portal hypertension localising that sodium
      and water in the peritoneum. Ascites is an important development in cirrhosis as
      it implies a generally poor long term prognosis. Investigation is important as
      ascites is not always dueto cirrhosis, may bethe consequence of complications of
      cirrhosis such as hepatocellular carcinoma, and may be associated with infection
      which is fatal if untreated. Most patients respond to treatment with sodium
      restriction and diuretic drugs. This treatment takes time, and increasingly
      doctors use therapeutic paracentesis with sodium restriction and diuretics to
      prevent recurrence of ascites. Paracentesis, however, is not without
      complications, and it is particularly important to give colloid replacement to
      prevent hypovolaemia which can lead to renal failure. Patients who do not respond
      to this treatment may be helped by a TIPSS procedure or a peritoneovenous shunt.
      However, these patients usually have very poor liverfunction and the possibility
      of fiver transplantation should be considered. Infection is a very serious
      complication of ascites (spontaneous bacterial peritonitis) and carries a
      generally poor prognosis.Antibiotic prophylaxis is important to prevent
      recurrence and liver transpiantation shoulcl be considered.

PMID- 12215742
TI  - [ARTIFICIAL NUTRITIONAL SUPPORT IN HIV INFECTION: REPORTOF ONE CASE]
AB  - The present work describes the first case of HIV infected patient admitted to
      nutritional therapy in a multidisciplinary Nutritional Support Unit in Peru, and
      is the first of this type published in Peru. We show the case of a teen-ager
      patient with severe gastrointestinal and nutritional alterations as a
      complication of HIV infection, who required parenteral total nutrition for 21
      days. During this treatment period we did not observe any complication as result
      of nutritional intervention; on the contrary, we observed a great clinical
      improvement and an adecuated nutritional response trough the most recognized
      biochemical parameters and using Body composition by Impedanciometry, a new
      technic for our country.

PMID- 12215743
TI  - [ALCOHOLIC HEPATITIS]
AB  - At present, the relation between alcoholic consumption and the development of
      hepatic injury is clearly defined. However, the influence of genetic factors, the
      existence of associated pathologies, and the concomitant use of other hepatotoxic
      agents should also be considered.During chronic drunkenness, great quantities of
      oxygen free radicals are produced, redox balance is disturbed, and the defensive
      capacity of natural antioxidants is exceeded. All these factors originate an
      "oxidative stress," that totally distorts the hepatocellular function. Llkewise,
      an increase in the acetaldehyde intracellular concentration modifies several
      cellular proteins, deteriorating even more the hepatic activity. The importance
      of the "neo-antigens" between cellular components and acetaldehyde is still
      undefined, as well as their role in the formation of the Mallory Bodies.On the
      other hand, the complex network of intercellular and intracellular communications
      that includes cytokines, adherence molecules and membrane receptors are essential
      elements to be considered in the alcoholic liver disease genesis. The endotoxin,
      the TNF-a, the IL-8, as well as the ROIs production seem to be the most important
      factors.With reference to Alcoholic Hepatitis, the development of an exaggerated
      inflammatory response with the existence of neutrophiles may be the main
      mechanism of hepatocellular injury (82, 167, 168.)The final diagnosis of
      Alcoholic Hepatitis is histological. This also enables to measure the injury
      severity and to determine the presence of fibrosis and/or cirrhosis, in which
      case prognosis is more uncertain.Should a history of exaggerated alcoholic
      ingestion exist, diagnosis could be clinically determined. There is a great
      variability of clinical symptoms, and some patients present chronic liver disease
      complications frequently. Those who develop severe liver insufficiency will
      present leukocytosis, icterus and fever. In these cases, mortality can be as high
      as 80 per cent. There is no relationship between the alteration of liver function
      tests and the injury severity.The usefulness of antioxidants in cirrhosis has
      been demonstrated in animal modeis and in some studies made in human voluntarles.
      However, their role as therapy within the context of Alcoholic Hepatitis has not
      been yet defined.In conclusion, several therapeutic approaches have been
      investigated and from all of them, only steroids have proven to be effective on
      patients properly selected. The discriminative function (DF) benefit has been
      confirmed in certain studies. Should a patient have a DIF of more than 93, he/she
      may receive corticosterold treatment. Contral ndicati ons are a bsol ute when the
      patientpresents infection, renal insufficiency or gastrointestinal bleeding.Once
      the patient has been compensated, ABSTINENCE is essential. Likewise, an
      appropriate nutritional support is an important part of the treatment.Where the
      possibility of Liver Transplant exists, this should be planned if there is a
      deterioration of the patient's general condition or if he/she compiles with the
      necessary criteria, since the survival rate in these cases is similar to those
      who received a transpiant due to other causes.

PMID- 12215745
TI  - Funding partnerships for chronic disease research.

PMID- 12215747
TI  - Profile of the cardiovascular specialist physician workforce in Canada.
AB  - The Canadian Cardiovascular Society conducted a comprehensive survey of 2267
      cardiovascular specialist physicians in Canada to profile the type of services
      provided, physician workloads and expectations of future practice patterns. The
      survey snapshot of these activities was supplemented with data from the Canadian
      Institute for Health Information on historical numbers of physicians and key
      procedure volumes, and the Canadian Medical Association's template for estimates
      of the future supply of physicians. Together, these data sources highlight the
      growth in procedure volumes that has exceeded the growth in the supply of
      cardiovascular specialist physicians.

PMID- 12215748
TI  - Head-up tilt table testing with low dose sublingual isosorbide dinitrate in the
      evaluation of unexplained syncope: a comparison with isoproterenol infusion.
AB  - OBJECTIVES: To investigate the value of head-up tilt table testing (HUTT) with
      low-dose isosorbide dinitrate (ISDN) in the evaluation of patients with
      unexplained syncope and to compare the results of HUTT with ISDN and HUTT with
      isoproterenol. PATIENTS AND METHODS: Forty-three patients with unexplained
      syncope (21 women, with a mean age of 45.4 18 years) and 18 control subjects
      without syncope (eight women, with a mean age of 45.8 12 years) were tilted (80 )
      for 30 min (passive period). When this period was negative, 2.5 mg sublingual
      ISDN was administered and patients were observed for an additional 15 min (ISDN
      period). The first 25 patients studied (10 women, with a mean age of 46.2 18
      years) were tested again after a mean period of three weeks using the
      isoproterenol protocol. After the passive period, intravenous isoproterenol was
      administered (1 to 3  g/min) to patients lying in the supine position, and they
      were tilted again (80 ) for 10 min (isoproterenol period). RESULTS: During the
      passive period, 10 of 43 patients (23%) had a positive response compared with
      none in the control group. Syncope was observed in another 14 patients and in two
      control subjects during the ISDN period. The positivity rate (sensitivity) and
      specificity of HUTT with low dose ISDN were 56% and 89%, respectively. Among the
      patients (n=25) tested with the isoproterenol protocol, 14 (56%) patients had
      syncope. The agreement rate between the protocols was 78.9%. CONCLUSIONS: The
      total positivity rate of HUTT significantly increased with the use of the low
      dose ISDN, while specificity remained high. Due to its simplicity and
      tolerability, the ISDN protocol can be chosen when the results of the passive
      period tilt testing are negative.

PMID- 12215749
TI  - Cardiovascular disease in Chinese Canadians: a case-mix study from an urban
      tertiary care cardiology clinic.
AB  - BACKGROUND: Cardiovascular diseases (CVD) are the leading cause of death in
      Canada. Non-European ethnic groups such as the Chinese constitute an increasingly
      significant sector of the Canadian population. OBJECTIVE: To compare the
      frequency and risk factors of CVD in Chinese and white Canadians in a cardiology
      referral clinic that saw a high number of ethnic Chinese patients and provided
      equal access to advanced diagnostic facilities. PATIENTS AND METHODS: Clinic
      charts of patients referred between 1994 and 1999 were reviewed. Patients of
      Chinese descent were identified by their names. Primary cardiovascular and
      secondary cardiovascular diagnoses, as well as risk factors for coronary artery
      disease (CAD), were established. The frequency of disease and risk factors were
      age-standardized. RESULTS: The sample of patients with CVD consisted of 404
      Chinese and 1129 white subjects. Chinese patients were older (median age 65
      versus 62 years, P=0.006). CAD, heart failure and peripheral vascular disease
      were less frequent in Chinese than in white patients. On the other hand, valvular
      heart disease was more frequent in Chinese patients. Diabetes, smoking and family
      history of heart disease were less frequent in Chinese subjects, whereas the
      frequencies of hypertension and hypercholerolemia were similar to those of white
      patients. In patients who had undergone coronary angiography, the frequency of
      multivessel CAD was less in Chinese patients (40% versus 56%, P=0.0016). Angina
      pectoris was a more common manifestation of CAD in Chinese patients, whereas
      myocardial infarction was more common in people who were white. In patients with
      heart failure, the median left ventricular ejection fraction was higher in
      Chinese than in white patients (34% versus 28%, P=0.031). CONCLUSIONS: In
      patients referred to a cardiology clinic, the diagnosis of CAD and the majority
      of other CVDs was less frequent in Chinese Canadians than in white Canadians.
      However, selected modifiable risk factors for CAD, such as hypertension and
      hypercholesterolemia, were equally frequent. Further research at the population
      level is warranted to define the characteristics of CVD in Chinese Canadians, and
      may be useful to the future design of disease management and prevention programs
      tailored to the needs of this growing ethnic population.

PMID- 12215750
TI  - Increased AT2R protein expression but not increased apoptosis during
      cardioprotection induced by AT1R blockade.
AB  - BACKGROUND: The angiotensin II type 2 receptor (AT2R) is considered to be
      antigrowth and to mediate apoptosis in several cell types. Whether AT2R
      upregulation, associated with angiotensin II type 1 receptor (AT1R) blockade and
      cardioprotection after ischemia-reperfusion (IR), might not result in increased
      cardiomyocyte (CM) apoptosis has not been documented. OBJECTIVES: To determine
      whether increased AT2R protein expression, during AT1R blockade after acute IR,
      is associated with no increase in CM apoptosis. MATERIALS AND METHODS: The
      recovery of left ventricular (LV) mechanical function after acute IR (30 min of
      ischemia, 40 min of reperfusion) was measured in isolated Langendorff rat hearts
      following pretreatment with the AT1R antagonist candesartan (CN) (CN 10 nmol/L)
      for 40 min before ischemia. The authors established with an initial dose-response
      curve using escalating concentrations of CN that 10 nmol/L abrogated
      vasoconstriction induced by angiotensin II (0.1 mmol/L). AT1R and AT2R protein
      expression (Western immunoblot), CM apoptosis (terminal deoxynucleotidyl
      transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end-labelling assay and
      nuclear morphology) and apoptotic markers (Bax, Bcl-2, caspase-3, p53) were
      assessed in LV tissue. RESULTS: Compared with IR controls, CN improved peak
      systolic pressure, LV developed pressure and positive dp/dt, and increased AT2R
      (not AT1R) protein, but did not change the level of apoptosis or the expression
      of Bax, Bcl-2, caspase-3 or p53. CN also increased AT2R protein after ischemia
      alone but did not change CM apoptosis or expression of the markers. CONCLUSIONS:
      Increased AT2R protein expression during AT1R blockade after IR in the isolated
      Langendorff rat heart is associated with cardioprotection but no increase in CM
      apoptosis.

PMID- 12215751
TI  - Transvenous pacemaker malposition in the systemic circulation and pacemaker
      infection: a case report and review of the literature.
AB  - Transvenous pacemaker malposition in the systemic circulation is a rare
      complication of pacemaker implantation; the incidence is not well known. However,
      with the aid of two-dimensional echocardiography, the problem of pacemaker
      malposition can be identified earlier. After pacemaker insertion, an
      electrocardiogram and a posterior-anterior and lateral chest x-ray should be
      routinely performed. In difficult cases, transthoracic echocardiography and
      transesophageal echocardiography can be helpful for better visualization and
      confirmation of the malposition of the pacemaker lead(s). Pacemaker infection is
      another complication. A case of pacer lead malposition into the left ventricle
      through a sinus venosus atrial septal defect and superimposed infection is
      reported, and the management of endocardial lead malposition in the systemic
      circulation and pacemaker infection is reviewed.

PMID- 12215753
TI  - Reflection from the seashore II.

PMID- 12215752
TI  - Harken prosthetic valve thrombosis.

PMID- 12215754
TI  - [Thrombin inhibitors--current developments and clinical relevance].

PMID- 12215755
TI  - [Rationale for an oral thrombin inhibitor from a pharmacological point of view].
AB  - Direct thrombin inhibitors are in focus of interest for hereditary or acquired
      thrombophilic indications. Besides thrombosis prophylaxis in surgery, life
      threatening cardiac diseases and stroke are of special interest for this new drug
      class. For long-term prophylaxis of genetically caused thrombophilia the only
      drug class currently available are the orally active dicoumarol derivatives.
      Their application is a time and cost intensive procedure and associated with side
      effects, too. Active site-directed inhibitors block the catalytic triad of the
      active centre of thrombin responsible for hydrolytic cleavage. Inhibitor ratios
      (K(j)) are in the nanomolar or picomolar range. As these substances are
      eliminated via liver or kidneys with an elimination half-life of 0.3-2 hours,
      parenteral administration should be used for acute therapy and prophylaxis. For
      long-term prophylaxis, orally absorbable derivatives of these direct thrombin
      inhibitors are available with absorption rates of 10-30%. They are converted into
      their parent substance in blood. Therapeutical range is relatively large so that
      an oral long-term prophylaxis using standard dose is possible without monitoring.
      The first representative of this new drug class, Ximelagatran, an orally
      absorbable variant of Melagatran, is currently undergoing phase III trials for
      different indications. Using oral administration of two partial doses per day, a
      good compliance is expected.

PMID- 12215756
TI  - [Anticoagulation: the present and the future].
AB  - Because of its central role in the coagulation cascade thrombin is an attractive
      target for its inhibition. Many limitations of conventional anticoagulants have
      been eliminated by the development of the direct oral thrombin inhibitor
      ximelagatran. Thus, this compound may fulfil the criteria of an ideal
      anticoagulant. The antithrombotic efficacy and safety of this inhibitor is
      presently studied in a large clinical development program.

PMID- 12215757
TI  - [The oral direct thrombin inhibitor Ximelagatran Prophylaxis of venous
      thromboembolism in hip and knee replacement].
AB  - AIM: The efficacy and safety of the new oral, direct and selective thrombin
      inhibitor Ximelagatran and its active form Melagatran was analysed in patients
      undergoing total hip or knee replacement. METHODS AND PATIENTS: Methro II, a
      randomised, double-blind controlled dose-finding study, involved 1876 patients.
      Melagatran (1, 1.5, 2.25 or 3 mg; twice daily; start: immediately before surgery)
      was given subcutaneously, followed by orally administered Ximelagatran (8, 12, 18
      or 24 mg, twice daily, day after surgery) and compared to subcutaneously
      administered dalteparin (5000 IE, once daily). Methro III was a randomised,
      double blind controlled study involving 2788 patients. The fixed dose of 3 mg
      Melagatran was given (start: 4-12 hours postoperatively) followed by oral
      Ximelagatran (24 mg, twice daily, day after surgery) compared to subcutaneous
      enoxaparin (40 mg, once daily). In both studies, dalteparin or enoxaparin was
      applied at the evening before operation; the treatment lasted 8 to 11 days. A
      bilateral venography was performed at the last day of treatment. RESULTS: In the
      Methro II study, 1270 patients underwent total hip, 606 total knee replacement.
      In both groups the thromboembolism rate was reduced depending on the dose of
      Ximelagatran/Melagatran. Compared to dalteparin, it was significantly lower for
      the Ximelagatran/Melagatran group with the highest dose. In the Methro III study
      1923 patients underwent a total hip, 865 a total knee replacement. The
      thromboembolism rate was 31% for the Ximelagatran/Melagatran group compared to
      27% for the enoxaparin group. In both studies blood loss and transfusion
      requirement were in the same range as with low weight molecular heparins.
      CONCLUSIONS: A fixed subcutaneously given dose of Melagatran, followed by orally
      administered Ximelagatran is effective and well tolerated as prophylaxis against
      venous thromboembolism.

PMID- 12215758
TI  - [Ximelagatran for treatment of venous thromboembolism].
AB  - Acute venous thromboembolism including asymptomatic and symptomatic pulmonary
      embolism without respiratory or cardiac failure is currently treated for 6
      months, initially with subcutaneous low-molecular-weight heparin followed by oral
      anticoagulation. The main drawback of oral anticoagulation is caused by severe
      bleeding complications. Oral Ximelagatran has shown to be as effective and safe
      for the initial treatment of acute deep venous thrombosis compared to
      subcutaneous low-molecular-weight heparin followed by oral warfarin over a period
      of 4 weeks. Currently, oral ximelagatran is investigated versus subcutaneous low
      molecular-weight heparin and oral warfarin over 6 months to demonstrate an almost
      equal efficacy and safety. The study is performed on a double blind and double
      dummy basis. Six months after oral anticoagulation of patients with acute deep
      venous thrombosis, recurrent venous thromboembolism may occur in up to 25% within
      2 years. Ximelagatran is currently investigated versus placebo to demonstrate a
      reduced recurrence rate of venous thromboembolism over a period of 18 months.

PMID- 12215759
TI  - [New developments in anticoagulation therapy for Ione atrial fibrillation].
AB  - Lone atrial fibrillation is a major health problem for elderly patients with
      cardiovascular risk factors as hypertension, congestive heart failure or previous
      myocardial infarction. The increased stroke rate of these patients is
      significantly reduced by oral anticoagulation (target: INR 2-3) and less
      effective by acetylsalicylic acid at a dose of 325 mg/d. As an alternative to the
      vitamin K-antagonistic anticoagulants currently the SPORTIF trial program is
      performed investigating the safety and efficacy of the oral direct thrombin
      inhibitor ximelagatran. Recent data derived from a dose-finding study and its
      open label continuous follow-up period are very encouraging with regard to the
      low incidence of bleeding complications and ximelagatran's clinical efficacy for
      the prevention of thromboembolic events. Large confirmatory trials engaging about
      3000 patients each are under way in Europe as an open-label trial and the United
      Staates as a double blind trial. Results are being expected for the end of year
      2002. These data will clarify the role of ximelagatran for the prevention of
      thromboembolic events in patients with lone atrial fibrillation and may give us
      an insight into a new standard drug regimen for stroke prevention in high risk
      patients.

PMID- 12215760
TI  - [Future potential indications for an oral thrombin inhibitor].
AB  - By the use of conventional anticoagulants, significant improvements were achieved
      in all fields of medicine. Although efficacious and widely used, their use is
      limited in several respects. In particular, the use of vitamin K antagonists is
      restricted in the clinical routine setting. The main reasons are the delayed on-
      and off-set of action, the narrow therapeutic window, the necessity of individual
      laboratory-controlled dosing, and interactions with food ingredients and drugs.
      The search for new antithrombotics with an improved safety/efficacy profile led
      to the development of the direct oral thrombin-inhibitor ximelagatran. It can be
      administered without routine monitoring of coagulation parameters and does not
      possess any of the previously mentioned limitations. The results from clinical
      phase II studies obtained so far are very encouraging. After completion of the
      clinical development program focussing on prevention and treatment of venous
      thromboembolism, on stroke prevention in atrial fibrillation and on acute
      coronary syndromes, it is desirable to continue with investigations with regard
      to long-term prophylaxis in high risk surgery, in chronic peripheral artery
      disease, in patients with left ventricular thrombi, artificial heart valves, or
      thrombophilia, as an alternative anticoagulant in heparin induced
      thrombocytopenia and for prevention of thromboembolic complications in oncology.
      Because of the mitogenic effects of thrombin on the proliferation of tumour
      cells, additional experimental studies aiming at a potential inhibition of
      thrombin-triggered oncogenesis is of uttermost interest.

PMID- 12215761
TI  - [Hirudins in the treatment of heparin-induced thrombocytopenia and in thrombosis
      prophylaxis].
AB  - Approved indications for the recombinant hirudins lepirudin (Refludan(R)) und
      desirudin (Revasc(R)) are therapy of heparin-induced thrombocytopenia (HIT) and
      thrombosis prophylaxis following knee or hip replacement surgery. Kidney function
      dependent pharmacokinetics and their capability of inducing antibodies directed
      against hirudin are characteristic of this class of drugs. However, close dose
      monitoring allows safe and effective use of both compounds. While lepirudin is
      used widely, besides danaparoid, for treatment of HIT, desirudin has not yet been
      widely accepted for thrombosis prophylaxis following knee or hip replacement
      surgery.

PMID- 12215762
TI  - [Experimental and clinical results with the thrombin inhibitor Argatroban].
AB  - Argatroban is the smallest anticoagulant molecule of direct thrombin inhibitors.
      The main attributes of this synthetic drug are its rapid onset of anti-thrombin
      action, the rapid reversibility of its anticoagulant effect, potent inhibition of
      clot-bound thrombin, the absence of antibody formation and no need for dosage
      adjustment in patients with renal impairment. It is eliminated by hepatic
      metabolism. These properties make argatroban a predictable anticoagulant with
      intravenous use in a routine clinical setting. Argatroban is approved in the US
      and Canada for both prophylaxis and treatment of thrombosis in patients with
      heparin-induced throm-bocytopenia (HIT) and in the US as an antithrombotic agent
      during percutaneous coronary interventions in patients with HIT or a history of
      HIT. Preliminary reports document the feasibility of using argatroban for
      anticoagulation during hemodialysis and as adjunct to thrombolysis for treatment
      of myocardial infarction. Current recommendations for argatroban monitoring are
      to use the aPTT (activated partial thromboplastin time) for low doses and the ACT
      (activated clotting time) for high doses. The specific inhibition of thrombin can
      be measured with the ECT (ecarin clotting time).

PMID- 12215763
TI  - Bivalirudin, a bivalent, thrombin specific anticoagulant as an alternative to
      heparin in interventional procedures as an alternative to heparin in
      interventional procedures.
AB  - Among the antithrombotic therapies evaluated to date, the synthetic peptide
      bivalirudin is unique in its ability to reduce both ischemic and bleeding
      complications associated with percutaneous coronary intervention (PCI).
      Bivalirudin is a small peptide consisting of 20 amino acid residues that binds
      thrombin in a direct, reversible, and bivalent fashion. The agent is approved for
      use in the United States and New Zealand as an anticoagulant in patients with
      unstable angina undergoing PCI and may also prove beneficial in patients with
      acute coronary syndromes (ACS), acute myocardial infarction (AMI) and in patients
      undergoing coronary artery bypass graft (CABG) procedures. This article examines
      bivalirudin in more detail.

PMID- 12215764
TI  - The ESR and UV-VIS Studies on the Reaction Between Ascorbic Acid and Iron Ion.
AB  - With ESR spin trapping methods and UV-VIS spectrometry, the reaction between
      ascorbic acid and iron ion was studied. It was found that one mole of ascorbic
      acid was able to reduce four moles of ferric ions, but no ESR signal of any
      radical was observed. Based on the above experiments the mechanisms of these
      reactions were suggested and effects of ascorbic acid in antioxidation and the
      promoting of oxidation were discussed.

PMID- 12215765
TI  - The Accumulation of Diacylglycerol and Activation of Protein Kinase C by Caffeine
      Treatment in Frog Skeletal Muscle.
AB  - Our previous work has shown that high K(+) exposure could induce an accumulation
      of diacylglycerol (DAG) and the activation of protein kinase C (PKC) in frog
      skeletal muscle. To elucidate its mechanism, the effect of caffeine on the
      pathway of DAG/PKC signal transduction was investigated. Caffeine could induce
      DAG accumulation and PKC activation in a dose- and time-dependent manner. The
      accumulation of DAG induced by caffeine was significantly different from that
      produced by high K(+) exposure, although the intracellular calcium was raised to
      a similar peak. In addition, differences in the activation of PKC were shown
      between caffeine and high K(+) exposure. These differences suggest that the
      myoplasmic calcium increase produced by high K(+) exposure is not a sole factor
      for the activation of DAG/PKC signal transduction in frog skeletal muscle, and
      the high K(+)-induced depolarization may play some roles.

PMID- 12215766
TI  - Structure Prediction and Analyzing of the Molecular Chaperone TCP1.
AB  - An improved Chou and Fasman method and the Robson method from Prosis software
      were applied to four TCP1s and five homologous proteins. The predictive results
      showed that there may exist two structural domains in TCPI with a "hinge region"
      between them, suggesting that the two structural domains may be alpha/beta
      barrels. The putative ATP-binding domain, whose motif centres around the absolute
      conserved GDGTT sequence at position 87-91 in TCP1Hu, was found to be a coil
      region in the predictive results.

PMID- 12215767
TI  - Construction of Urokinase Mutant Glu154-mtcu-PA and Characterization of Its
      Properties.
AB  - The recombinant single chain urokinase-type plasminogen activator (rscu-PA) and a
      mutant constructed by in vitro site-specific mutagenesis of Argl54 in rscu-PA to
      Glul54 (Glul54-mscu-PA) were both expressed in E. coli. The expressed products
      were both purified to homogeneity by in vitro denaturation and renaturation,
      followed by Zn(2+) selective precipitation and immuno-affinity chromatography.
      The plasmin sensitivity assay indicated that the activation of this single chain
      Glul54-mscu-PA by plasmin was essentially identical to that of rscu-PA. After
      activation by plasmin, the kinetic constants against synthetic substrate S2444 of
      the resulted two chain form of Glul54-mscu-PA (Glul54-mtcu-PA) and that of rscu
      PA (rtcu-PA) were 87 &mgr;M and 80 &mgr;M, respectively, which indicated that the
      catalytic active site of the Glul54-mtcu-PA was not changed by the mutation.
      Whereas, both (125)I-fibrin plasma-clot lysis and fibrinogenolysis in plasma
      showed that the Glul54-mtcu-PA possessed a better affinity and selectivity for
      fibrin than rtcu-PA, even better than rscu-PA.

PMID- 12215768
TI  - PMA Stimulated Hydrolysis of Phosphatidylcholine in CRBH7919 Cell and Its
      Enzymatic Basis.
AB  - The effect of phorbol 12-myristate-13-acetate (PMA) on the hydrolysis of
      phosphatidylcholine (PC) in rat hepatoma cell line CRBH7919 has been studied. It
      was found that PMA stimulated PC hydrolysis in CRBH7919 cells in a dose-dependent
      manner after treatment for 15 min. The product of PC hydrolysis was choline, not
      phosphocholine. The activity of the membrane bound PC-specific phospholipase D
      (PC-PLD) was determined. The results showed that the activity of PC-PLD increased
      after 10 min with 100 nM PMA treatment, and reached a level 3.25 times the
      control after 30 min. The fact that the PC-PLD activation preceded the hydrolysis
      of PC, suggests that PC-PLD is involved in the PC hydrolysis into phosphatidic
      acid and choline in CRBH7919 cells in the presence of PMA.

PMID- 12215769
TI  - High Expression in Insect Cells of A Functional Chimeric Antibody with
      Specificity for HBsAg.
AB  - We have constructed a double-recombinant virus BacHL4.2 containing both the
      chimeric heavy- and light-chain cDNAs from monoclonal antibody of the HBsAg gene.
      Both murine-human chimeric antibody heavy- and light-chain were expressed in Sf9
      cells infected with a double-recombinant virus BacHL4.2 or co-infected with
      separate heavy- and light-chain recombinant viruses. In both cases, expressed
      products were correctly assembled into normal H(2)L(2) immunoglobulin monomers.
      ELISA and functional immunoblot assay showed that the recombinant chimeric
      antibody exhibited a specificity for HBsAg similar to that of the parental murine
      monoclonal antibody OH3.

PMID- 12215770
TI  - A Study of the Myocardial Nuclear Calcium Transport of Rabbit in vitro.
AB  - The characteristics of nuclear calcium regulation were investigated in isolated
      rabbit myocardial nuclei. It was found that calcium concentration in myocardial
      nuclei was 2.6 fold more than that in myocardial homogenate (P<0.O1), and the
      nuclear calcium content was only l/6 of the total cellular calcium. Ca-ATPase of
      myocardial nuclei was [Ca(2+] and [ATP] dependent. [Ca2+] dependent K(a) and
      V(max) at 2.O mmol/L [ATP] were 226 nmol/L and 3 460 nmol/(h.mg) protein
      respectively. [ATP] dependent K(m) value and V(max) at 400 nmol/L [Ca2+] were
      376.5 &mgr;mol/L and 2 445 nmol/(h.mg) protein respectively. A positive
      correlation between nuclear 45)Ca2+ transport and Ca-ATPase activity was observed
      (r=O.945, P<0.01). The above result suggests that myocardial nuclei are able to
      transport calcium actively. The pathophysiological role of myocardial nuclear
      calcium transport should be further determined.

PMID- 12215771
TI  - The Properties of Serum GPI-PLD.
AB  - The purified glycosylphosphatidylinositol phospholipase D (GPI-PLD) is a single
      polypeptide with a molecular weight of about 1OO kD. However, the enzyme is
      eluted in the fraction of 500 kD when human serum undergoes gel filtration
      chromatography. To study the natural state of GPI-PLD might help to visualize its
      physiological function. By using gel filtration, hydrophobic column
      chromatography and ultracentrifugation, and analyzing the concentration of
      phospholipids, triglycerides and cholesterol, we found that GPI-PLD did not exist
      as polymer of polypeptids in serum, but combined with the serum lipids to form a
      complex of lipids and proteins. As a result, it is present in a density zone
      similar to HDL after ultracentrifugation, this complex exists in serum separately
      from the subfractions of HDL which are abundant in Apo-A1. In addition it could
      bind on the heparin-Sepharose affinity chromatography column as Apo-E.

PMID- 12215772
TI  - The Involvement of Plastoquinone in the Pyocyanine-mediated Cyclic Electron
      Transport around Photosystem I.
AB  - 2,5 dibromo-3-methyl-5-isopropyl-p-benzoquinone (DBMIB), an inhibitor of
      plastoquinone, inhibited photosystem I cyclic electron transport mediated by
      pyocyanine of low concentration, but had no effect on that mediated by phenazine
      methosulphate (PMS). In the presence of pyocyanine, the thylakoids displayed a
      transient post-illumination increase in chlorophyll fluorescence which resembled
      that displayed in leaves. The above results indicate the involvement of
      plastoquinone in the pyocyanine-mediated cyclic electron transport around
      photosystem I.

PMID- 12215773
TI  - Purification and Characterization of the Trypsin Inhibitor from Sophora
      alopecuroide L. 
AB  - Sophora alopecuroide trypsin inhibitor (SATI) was purified from the seeds of
      Sophora alopecuroide L. by affinity chromatography on trypsin-sepharose 4B. The
      inhibitor is homogenous on SDS-PAGE (12%), which is a single polypeptide chain
      with alanine as its N-terminal. It has the molecular weight of 18 kD and pI at
      9.3. Results also show that the inhibitor has a 1:2 molar inhibitory ratio of
      inhibitor to trypsin. In further study with the method of modification, the
      residues of argenine and lysine are found to be the only 2 reactive centers on
      the inhibitor. Feeding trials on cotton aphid indicated that the inhibitor has
      relatively strong anti-cotton aphid activity with LC(50) (half lethal
      concentration) of 87.2 mg/L and LD(50) (half lethal dosage) of 6.796 &mgr;g
      (feeding for 120 h).

PMID- 12215774
TI  - The Overproduction of Leucyl-tRNA Synthetase in E. coli and Its Purification.
AB  - The 3.2 kb gene (leuS) encoding for leucyl-tRNA synthetase (LeuRS) has been
      cloned from E.coli K-12, and overexpressed 35 times more than that in the host
      strain TG1. In order to further increase the production of LeuRS, two types of
      leuS with different length of the 3' flanking region: leuS1 has an additional 130
      bp over that of leuS2 were ligated into pKK-233-2 and pTrc-99B, respectively. In
      E. coli TG1 transformant harboring the recombination plasmid pTrc-99B with leuS2,
      the yield of LeuRS was 135 times that in TG1 strain. The purified enzyme that
      showed one band on SDS-PAGE was obtained after two steps of column
      chromatography. During the construction of plasmid, a substitute of G for C was
      introduced at position of base 4 in the coding region of leuS, so that Gln2 of
      LeuRS was changed to Glu. This enzyme was designated LeuRS2E. The kinetic
      constants of LeuRS2E showed that the substitution has no effect on the enzyme
      activity and could be used in the studies of LeuRS as the native enzyme.

PMID- 12215775
TI  - The Interaction of Recombinant Androgen Receptor with the Androgen Responsive
      Element.
AB  - A 1 119 bp (1105 to 2224) fragment of androgen receptor (AR) cDNA, named AR1
      (containing the whole DNA binding domain, the hinge site region and the partial
      hormone binding domain) was constructed into an expression vector pGEX. The GST
      ARI fusion protein was expressed in E. coli induced by IPTG and purified from
      glutathione-Sepharose-4B affinity column. With a known ARE of the C3(l) gene as
      positive probe, the expressed product was proved to be AR with high ARE-binding
      affinity by gel shifting assay(EMSA) and in vitro Dnase I footprinting analysis.

PMID- 12215776
TI  - Isolation and Partial Purification of Two Types of Nuclear Tyrosine Protein
      Kinase from Rat Liver.
AB  - Nuclear tyrosine protein kinase (n-TPK) plays an important role in the regulation
      of cell cycle and gene transcription. In the present investigation, two types of
      n-TPK isozyme, n-TPK I and n-TPK II were isolated from the nuclear extract of rat
      liver by using DEAE-Sepharose CL-6B ion-exchange column chromatography. The two
      isozymes were further partially purified on heparin affinity column and Sephadex
      G-100 to 30 and 25 folds respectively. The specific activities of n-TPK I and n
      TPK II were 1 638 and 1 360 pmol/(min.mg protein) respectively. By means of
      Sephadex G-100 chromatography and autoradiography of the autophosphorylated n-TPK
      after [32P]-ATP labeling and SDS-PAGE, the molecular weight of n-TPK I and n-TPK
      II were determined to be 76 kD and 59 kD respectively. Both n-TPK isozymes are
      monomers.

PMID- 12215777
TI  - Purification and Characterization of the Fibrinolytic Enzyme(eFE-D) from
      Earthworm Eisenia folelide.
AB  - The fibrinolytic enzyme eFE-D was isolated and purified from earthworm Elsenia
      folelide by gel-filtration on Sephacryle S-200, ion-exchange chromatography on
      DEAE-Sepharose Fast Flow and hydrophobic chromatography on Phenyle-Sepharose Fast
      Flow as detected by the fibrinolytic activity with a standard fibrin plate
      method. The most strong fibrinolytic component eFE-D not only hydrolyzed fibrin
      directly, but also activated the plasminogen to plasmin. Its apparent
      fibrinolytic value was equal to 2,800 UK IU per mg. Its molecular weight as
      estimated by SDS-PAGE and MS analysis was 29 kD and 24.849 kD respectively and
      its isoelectric point (pI) was 4.O. Fibrinolytic enzyme eFE-D was very
      thermostable with a single polypeptide chain. Studies with protease inhibitors
      indicated that eFE-D was a kind of serine protease. Its N-terminal amino acid
      sequence is M-I-G-G-T-N-A-S-P-G-E-F-P-W-Q-L-S-Q-Q-R. The result of amino acid
      composition analysis showed that the enzyme contained abundant amino acids of low
      molecular weight, but few aromatic and alkaline amino acids.

PMID- 12215778
TI  - Cloning and High Expression in E.coli of a Chimeric Gene Coding for Rice Fructose
      l,6-bisphosphate Aldolase.
AB  - A chimeric gene (l 104 bp) coding for rice fructose-l,6-bisphosphate aldolase has
      been constructed by DNA recombination of a synthetic 5'- fragment (-24 to 272)
      and an RT-PCR amplified product at restriction site S fu I. The synthetic
      fragment was assembled from six oligonucleotides by T4 DNA ligase reaction
      according to a single-stranded DNA method (Chen H-B et al, Nucleic Acids Res
      1990, 18, 871-878), the PCR amplified fragment (217 - 1 080) was obtained by
      carrying out a PCR in the presence of rice cDNA as the template and both the 5'-
      and the 3'- primers. The whole gene was successively cloned into plasmids pWR13
      and pPLc2833, and highly expressed in E. coli to produce the expected product.
      After purification through stepwise precipitation and cation-exchange column
      chromatography, the recombinant aldolase showed an enzyme activity as high as
      (1l.0 +/- 0.3) units/mg with the turnover number = 27s(-1) and K(m) (FBP)=4.2
      &mgr;M by two different methods.

PMID- 12215779
TI  - Preparation of Unilamellar Immunoliposomes by Passing Reversed Micelles through
      Oil-water Interface.
AB  - A novel method for the preparation of unilamellar immunoliposomes is introduced.
      In this method, the aqueous phase is first encapsulated into reverse micelles
      passing through the oil-water interface, where the monolayer of lecithin embedded
      with antibody has been formed to self-assemble into immunoliposomes. The main
      advantages of this method are that the procedure of preparation is simple with
      high encapsulation yield and it is favorable for large scale production. As shown
      by negative staining electronic micrograph, the immunoliposomes are unilamellar
      and 100-500 nm in size. The UV spectra of immunoliposomes solution and lysis
      assay show that sheep anti-human IgG has been coated on liposomes.

PMID- 12215780
TI  - Cloning and Expression of the Gene Coding for the Fusion Protein rhGM-CSF/LIF.
AB  - A fusion gene was constructed in a plasmid in which the coding regions of human
      GM_CSF and LIF cDNAs were connected by a synthetic linker sequence encoding a
      short peptide G-S-G-G-S through DNA recombinant techniques. It was then subcloned
      into the pBV220 expression vector, and expressed in E. coli after transformation
      and temperature induction. The expressed protein named as rhGM-LIF was confirmed
      by Western blot. After purification, the determination of activities showed that
      rhGM-LIF exhibited both GM-CSF and LIF activities.

PMID- 12215781
TI  - Complete Assignment of (1)H-NMR Resonances of the King Cobra Neurotoxin CM-11.
AB  - The king cobra (Ophiophagus Hannah) neurotoxin CM-Il is long-chain peptide with
      72 amino acid residues. Its complete assignment of (1)H-NMR resonances was
      obtained using various 2D-NMR technologies, including DQF-COSY, clean-TOCSY and
      NOESY.

PMID- 12215782
TI  - Effects of Type I Collagen on the Uptake of Oxidized Low Density Lipoprotein by
      Macrophages.
AB  - In order to investigate the influence of collagen on the uptake of oxidized low
      density lipoprotein (ox-LDL) by macrophages, a type I collagen gel-macrophages
      system was established in vitro. The binding of ox-LDL, malondialdehyde (MDA)
      modified LDL and acetyl LDL to collagen was higher but the binding of 4
      hydroxynonenal (HNE)-modified LDL was lower than that of native LDL. When mouse
      peritoneal macrophages were cultivated on the collagen gel, the uptake of ox-LDL
      decreased dramatically. Most of the modified (125)I-LDL were bound to the
      collagen gel rather than degraded by macrophages. If the cells were treated with
      cytochalasin D (an inhibitor of non-specific phagocytosis of macrophages), the
      degradation of ox-LDL by cells decreased markedly in the absence of collagen.
      However, the degradation of ox-LDL by cells showed little change in the presence
      of collagen. These results suggest that the non-specific phagocytosis of ox-LDL
      by macrophages might be prevented when type I collagen is present.

PMID- 12215783
TI  - Purification and Characterization of the Core Antenna CP43 of Photosystem II.
AB  - The core antenna CP43 of photosystem II was purified from the PSII core complex
      of spinach by DEAE-Toyopearl-650S anion-exchange chromatography, using the mild
      nonionic detergent beta-dodecyl maltoside and high concentration of LiClO(4). At
      room temperature, the purified CP43 has a maximum absorption at 671 nm, a
      fluorescence maximum at 683 nm and doublet CD signals which indicated the
      presence of excitonic interactions between some chlorophylls. The pigment content
      of the CP43 was 20 - 21 Chl a per CP43 polypeptide as determined by a
      spectroscopic method. The results suggested that the purified CP43 was still in a
      native state. Moreover, the specific antiserum was obtained and identified.

PMID- 12215784
TI  - The Mutation of mRNA Translation Initiation Region Influences Gene Translation.
AB  - In order to investigate the relationship between the structure of the mRNA
      translation initiation region (TIR) and gene expression, We mutated multiple
      sites of the 5' end of IFN-alpha8 and GM-CSF genes by site-directed mutagenesis
      without changing their amino acid sequences. SDS-PAGE showed that the protein
      products of mutated genes increased greatly in recombinant clones, as compared
      with their native genes. RNA dot blot revealed that the difference of their
      corresponding amount of mRNA transcribed between the native and the mutated genes
      was negligible. These results imply that the elevated expressions are attributed
      mainly to increased translation level. The prediction of mRNA secondary structure
      suggests that the delta G of TIR may have close relations to the expression
      level.

PMID- 12215785
TI  - Separate Expression and Characterization of the Heavy- and the Light-chain of A
      HBsAg Specific Murine-human Chimeric Antibody in Insect Cells.
AB  - Both the heavy- and light-chain of a murine-human chimeric antibody with
      specificity for hepatitis B virus surface antigen have been expressed separately
      in a baculovirus expression system. The heavy- and light-chain variable region
      (VH and VL) genes encoding the marine-monoclonal antibody OH3 were combined with
      human gamma3 and kappa constant region genes to construct the murine-human
      chimeric genes, respectively. The transfer vectors containing the chimeric genes
      were cotransfected into Sf9 cells with linearized virus DNA and recombinant
      viruses were isolated by dot hybridization, PCR and Southern blot analysis. The
      chimeric heavy- and light-chain was expressed respectively in the recombinant
      viruses-infected insect cells and the characterization by Western blot and
      competitive ELISA demonstrated that both of the expressed chimeric heavy- and
      light-chain have the specificity of HBsAg binding.

PMID- 12215786
TI  - Preliminary Study on the Primary Structure of Dragline Fibroin from the Spider
      Araneus ventrocosus.
AB  - The amino acid composition of the dragline fibroin from the spider fibroin of the
      spider Araneus ventrocosus was analysed and compared with that of the fibroins
      from different species of spiders. By means of partial acid hydrolysis and high
      performance liquid chromatography, several peptide fragments of the dragline
      fibroin were purified. The amino acid sequence analysis showed the sequences of
      these peptides to be different from that of the fibroin from the spider Nephila
      clavipes except for one common fragment with the sequence of GYGPG.

PMID- 12215787
TI  - Sequencing Analysis of Oligodeoxynucleotide by Matrix-assisted Laser Desorption
      Ionization Time-of-flight Mass Spectrometry.
AB  - A mixed matrix alpha-cyano 4-hydroxycinnamic acid (alpha-Cyano)/3
      hydroxypicolinic acid (3HPA) was found to be a good matrix for the analysis of
      oligodeoxynucleotides by matrix-assisted laser desorption ionization time-of
      flight mass spectrometry ( MALDI-TOF-MS). Using the mixed matrix, a similar
      sensitivity was obtained for the different oligodeoxynucleotides: d(T)(10),
      d(A)(10) and d(C)(10). This methodology can be used in combination with the
      partial digestion of oligodeoxynucleotides by 5'- and 3'-exonucleases as a
      powerful tool for sequencing analysis of oligonucleotides.

PMID- 12215788
TI  - Sequence Analysis of the exo1 Gene Involved in the Exopolysaccharide Synthesis of
      Rhizobium huakuii.
AB  - The 2.6 kb fragment which can complement the Exo(-)Ndv(-)Fix(-) mutants of R.
      huakuii to Exo(+)Nod(+)Fix(+) was sequenced. The result revealed the presence of
      an open reading frame exo1, which encodes 340 amino acids. Analysis of the
      hydrophobicity plot of the putative protein indicated that it was a cytoplasmic
      protein. Exo1 displayed strong homology to the ExoU protein of R. meliloti, which
      was a glucosyltransferase. A transcriptional fusion to lacZ using the
      promoterless vector pMP221 showed that there were two regions with promoter
      activity in exo1. Pexo1a was identified upstream of exo1, and Pexo1b in the
      middle of exo1. Pexo1a probably contains the promoter of exo1 gene.

PMID- 12215789
TI  - Correlation between the Dynamic Changes of Lipids and Phospholipases during
      Induced Hepatocarcinogenesis.
AB  - The correlation between the dynamic changes of l,2-diacylglyceride (DAG),
      phospholipids and phospholipase during the diethylnitrosoamine-induced
      hepatocarcinogenesis in rat was studied. It was found that liver DAG increased to
      the first peak at week 8 and maintained on a higher than normal level until week
      14 when the second highest peak appeared, then gradually dropped. The composition
      of phospholipid was estimated simultaneously in order to elucidate the origin of
      DAG. It was discovered that only phosphatidylcholine (PC) and
      phosphatidylinositides decreased during liver carcinogenesis, suggesting these
      two phospholipids may be the origin of the increased DAG. PC was probably the
      major source of DAG, owing to the decreased amount of PIs which was not
      sufficient to generate the increased amount of DAG. Then the activities of PC
      specific phospholipase C (PC-PLC) and phospholipase D (PLD) were determined by
      means of enzyme-coupling colorimetric methods. The results showed that the marked
      elevation of these two enzymes at week 8 might be related to the first peak of.
      DAG concentration and the PC hydrolysed by PC-PLC might be responsible for the
      second peak of DAG at week 14. The decline of DAG after week 14 was possibly due
      to the gradually decrease of PLD activity beginning from week 10, but other
      unknown factors might also be responsible for this decline. The regulation of PC
      PLC and PLO by protein kinase C and related oncogenes were discussed.

PMID- 12215790
TI  - Mitochondrial Mechanisms of Bcl-2 on Ionizing Radiation-induced Apoptosis.
AB  - Low dose radiation induces apoptosis and Bcl-2 can inhibit apoptosis induced by a
      variety of stimuli. The effects and possible mechanisms of Bcl-2 on 4 Gy X-ray
      induced apoptosis in Bcl-2 transfected and untransfected cells were studied. The
      data present here suggested that overexpression of Bcl-2 significantly inhibited
      X-ray-induced apoptosis in CHO cells within 72 h. Further investigation
      demonstrated that Bcl-2 prevented the loss of mitochondrial membrane potential
      (deltapsim) induced by X-ray irradiation. It appears that overexpression of Bcl-2
      blocked the ionizing radiation-induced apoptosis. The maintenance of deltapsim
      plays an important role in the protective mechanism of Bcl-2 on ionizing
      radiation-induced apoptosis.

PMID- 12215791
TI  - Determination of the Secondary Structure of the king Cobra Neurotoxin CM-11.
AB  - The king cobra neurotoxin CM-11 is a small protein with 72 amino acid residues.
      After its complete assignments of (1)H-NMR resonance's were obtained using
      various 2D-NMR technologies, including DQF-COSY, clean-TOCSY and NOESY, the
      secondary structure was analysed by studying the various NOEs extracted from the
      NOESY spectra and the distribution of chemical shifts. The secondary structure
      was finally determined by MCD as follows: a triple-strand antiparallel beta sheet
      with I20-W26, R37-A43 and V53-S59 as its beta strands, a short alpha helix formed
      by W30-G35 and four turns formed by P7-K1O, C14-G17, K50-V53 and D61-N64.

PMID- 12215792
TI  - Inhibition of Glutamate Uptake by Superoxide Anion Radical in Rat Cortical
      Synaptosomes and the Protective Effect of Ebselen.
AB  - The inhibition of glutamate uptake by superoxide anion radical (O(-)(2).) in rat
      cortical synaptosomes and the protective effect of Ebselen was studied by
      radioisotope method. The exposure to xanthine/xanthine oxidase, a O(-)(2).
      generating system, resulted in a marked decrease of high-affinity glutamate
      transport in the synaptosomes. In parallel, the Na(+),K(+)-ATPase activity was
      also damaged, while the lactate dehydrogenase activity and the TBARS contents in
      synaptic culture were not affected. It suggests that the inhibition of glutamate
      uptake is related to the damage of Na(+), K(+)-ATPase by O(-)(2). Ebselen was
      showed to have a blocking effect on the glutamate uptake inhibition by O(-)(2).,
      probably through protecting the Na(+),K(+)-ATPase.

PMID- 12215793
TI  - Study on Endogenous Substrates for Calcineurin in Rat Synaptosome.
AB  - The inhibition of endogenous calcineurin activity with polyclonal antibody
      revealed the presence of 11 phosphoprotein substrates for this enzyme in adult
      rat cerebral cortex synaptosome as studied by high resolution two-dimensional
      PAGE and autoradiography. The changes of these endogenous substrates for
      calcineurin from newborn rat and adult rat cerebral cortex synaptosome were
      analyzed quantitatively by using digital image scanning system based on the 2-D
      software and simultaneous, comparison with those of whole rat brain was made.
      Some of them were shown to be expressed at higher levels on postnatal day 3 and
      believed to be the neuromodulin/GAP-43 as reported in its literature. The
      important role of calcineurin in nerve growth and development was discussed.

PMID- 12215794
TI  - The Isolation and Purification of Archaerhodopsin from Halobacterium sp. XZ515.
AB  - The claret membrane, instead of the purple membrane, was isolated when the
      conventional method for isolating purple membrane from Halobacterium halobium was
      applied to Halobacterium sp. XZ515. The SDS-PAGE results showed that only one
      protein, archaerhodopsin, existed in claret membrane with M. W. similar to BR.
      The method for isolating and purifying the archaerhodopsin, an intrinsic membrane
      protein, by detergent dissolution and hydrophobic chromatography on the column of
      octylsepharose, was also introduced. The pure archaerhodopsin showed the
      absorption spectrum similar to BR and was able to produce the M412 photoproduct
      in the photocycle under illumilation. It was concluded that this archaerhodopsin
      was a BR-like retinal protein.

PMID- 12215795
TI  - Study on the Structure of C-Phycocyanin in Spirulina platensis with Scanning
      Tunneling Microscope.
AB  - The C-phycocyanin (C-PC) trimmer was isolated from the blue-green alga Spirulina
      platensis, and scanning tunneling microscope (STM) was used to investigate its
      structure. High resolution STM images of C-PC were obtained. From the STM images,
      it could be observed that the C-PC molecules were disk-like in shape and the
      subunits of C-PC arranged in ring-like pattern with a channel in the center.
      After filter treatment, the folding of the polypeptide chains could be seen
      clearly. This is the first time to observe directly the topography of
      phycobiliprotein, and the results showed STM to be a powerful tool for the
      structural study of phycobiliproteins.

PMID- 12215796
TI  - Regulatory Effect of HBV Integrated Fragment on PCNA Promoter.
AB  - H7C is a HBV integrated fragment isolated from a human hepatocellular carcinoma,
      containing the promoter of preS2 and the C-terminal truncated preS/S open reading
      frame. We have studied the effect of the 3'-truncated preS/S on human
      proliferating cell nuclear antigen (PCNA) promoter by co-transfection of the
      expression plasmids. Result showed that the product, pKSH7C-Hpa I, which
      contained the intact H7C and the flanking cellular sequences, stimulated the
      expression from PCNA promoter dose-dependently, and its effect was 1-2 folds
      higher than that on SV40 promoter. However, two subclones, pKSH7C-XHX and pKSH7C
      XbH, which would not express preS/S, showed no stimulatory effect. Furthermore,
      when if the -45 bp ATF-like site was mutated, the activation effect became
      diminished. This showed that the ATF-like site might be important in mediating
      the transactivating process. This is the first report of the effect of a HBV
      integrated fragment on the promoter of a replicating protein factor.

PMID- 12215797
TI  - The Influence of Different Physicochemical Parameters of the Solvent On The
      Activity and Selectivity of Lipase.
AB  - The asymmetric esterification of octanoic acid with racemic 2-octanol catalyzed
      by a lipase from Pseudomonas sp. was investigated in several typical solvents. It
      was found that the catalytic activity and the enantioselectivity of the enzyme
      were governed by different physicochemical parameters of the solvent employed.
      While the former depended on the hydrophobicity (lgP) of the solvent, by contrast
      the latter was a function of the dielectric constant and the dipole moment. A
      mechanistic model for the binding site of the enzyme was postulated to
      rationalize this phenomenon based on the results of the kinetic studies of the
      reaction in some representative solvents.

PMID- 12215798
TI  - Expression of Human Low-affinity Nerve Growth Factor Receptor in Mammanlian
      Neural Cells and its Induction of Apoptosis.
AB  - Human low-affinity nerve growth factor receptor (p75NGFR) was amplified from
      human fetal brain by RT-PCR and ligated into the retrovirus expression vector pXT
      1. The cloned pXT-1/p75NGFR was packaged by PA37 cell line and the collected
      pseudovirus was used to infect neural cell line R2. The expression of p75NGFR on
      R2 cells at the RNA transcriptional and protein translation levels were
      demonstrated by Northern bloting and FITC-labeled immunological analysis. Further
      studies indicated that p75NGFR could induce apoptosis of neural cells in culture
      medium deprived of serum. Such cell death could be prevented by inhibitors of
      macromolecular syntheses such as actinomycin D and cycloheximidine.

PMID- 12215799
TI  - Study on the Relationship between Lipoprotein(a) Receptor and LDL Receptor.
AB  - Lp(a) receptor and LDL receptor on rhesus monkey liver cellular membrane were
      studied by Western blotting, to investigate whether Lp(a) and LDL metabolize
      through the same route. The experiment demonstrated Lp(a) receptor ( 300kD) and
      LDL receptor ( 185kD) to be different kinds of receptors. The result reveals that
      Lp(a) has its own metabolic pathway.

PMID- 12215800
TI  - Purification and Characterization of DNA Helicase BstH2 from Bacillus
      Stearothermophilus.
AB  - In the purification of DNA helicase BstH1 we have partially purified the second
      DNA helicase BstH2 from Bacillus Stearothermophilus through Polymin P
      precipitation, ammonia sulfate precipitation and chromatographic steps with DEAE
      cellulose, phosphocellulose, Blue-Sepharose, FPLC Superose 12, Mono Q and second
      Mono Q. The ATPase activity of BstH2 depends on Mg(2+) and is differentially
      stimulated by different types of nucleic acids. BstH2 has a maximal ATPase
      activity at 55 degrees. The ATPase activity is greatly inhibited by E. coli SSB
      or higher ionic strength. The DNA helicase activity of BstH2 depends on ATP and
      Mg(2+). BstH2 can unwind partial duplex DNA as well as blunt-ended duplex DNA. E.
      coli SSB stimulates the unwinding reaction catalyzed by BstH2.

PMID- 12215801
TI  - Non-radioactive Determination of Phosphorylation in Proteins or Peptides by
      Capillary Electrophoresis.
AB  - A new method of capillary electrophoresis was described which allowed the non
      radioactive determination of all O-phosphoamino acids in peptides or proteins. It
      involved a partial hydrolysis of the peptide bonds, the derivatization of an
      amino acid mixture with phenylisothiocyanate and the separation of all the PTH
      phosphoamino acids from other PTH-amino acids by capillary electrophoresis. The
      correlation coefficients of the linear least-squares regression curves of all the
      phophoamino acids in concentration ranging from 25 to 250 pmol/&mgr;l, were
      greater than 0.992 (n=6). Detection limits were in the fmol range. The method had
      been applied to the analysis of the phosphorylation sites in several model
      polypeptides and two nature phosphorylated proteins beta-casein and phosvitin.

PMID- 12215802
TI  - Oxidative Modification of Very Low Density Lipoprotein by Arterial Wall Cells.
AB  - Modification of VLDL by arterial wall cells was observed. After incubating VLDL
      (200 &mgr;g protein/ml) with bovine aortic endothelial cells (EC), rabbit aortic
      smooth muscle cells (SMC) or mouse peritoneal macrophages (Mpsi)for 24 hours, the
      TBARS in VLDL increased strikingly to 7.80+/-O.75, 1O.6+/-O.90 and 11.4+/-O.70
      nmol/mg-protein respectively, much higher than those of their controls (5.1O+/
      0.60, 7.20+/-0.89, 5.30+/-O.54 nmol/mg-protein). The cell-modified VLDL migrated
      faster than the controls on agarose electrophoregram and the SDS-PAGE of the
      apolipoproteins showed that apo B(100) of VLDL was degraded to fragments without
      distinct bands, while apo E was essentially kept intact. Phosphatidylcholine was
      hydrolyzed to lysophosphatidylcholine during the modification process. These
      changes were inhibited by BHT, indicating that the modification of VLDL was an
      oxidative process. The result suggests that since VLDL could be oxidatively
      modified by arterial wall cells including EC, SMC, Mpsi in vitro, suggesting the
      oxidative modification of VLDL may occur in vivo and play an important role in
      atherogenesis.

PMID- 12215803
TI  - Preliminary Studies on the Amino-acid Residues at Active Center of the Lysozyme
      from Raphanus sativus Leaves.
AB  - A 1ysozyme from Raphanus sativus leaves was purified by the method of affinity
      chromatography on a deaminated regenerated crab chitin column. The purified
      enzyme was crystallized and showed a single band on polyacrylamide gel disc
      electrophoresis. The functional groups at the active center of the enzyme were
      studied by the method of pH dynamics and chemical modification. It was found that
      carboxyl groups(Glu/Asp), tryptophanyl and histidyl residues were probably
      essential groups for the catalytic activity. The enzymatic activity was not
      affected when the enzyme was modified by reagents which could specifically react
      with tyrosyl, cysteinyl, arginyl and seryl/threonyl residues. It was inhibited by
      histamine and GlcNAc. The difference among Raphanus sativus lysozyme, HEWI and
      papaya lysozyme was discussed.

PMID- 12215804
TI  - His(6) Fusion Expression of Myristoyl-CoA: Protein N-myristoyltransferase in E.
      coli and its Purification.
AB  - Saccharomyces cerevisiae Myristoyl-CoA: protein N-myristoyltransferase (NMT) gene
      was cloned into a His(6)-fusion expression vector pMFHT. After transforming into
      E. coli BL21 (DE3), His(6)-NMT was induced to express at 37 degrees by IPTG. SDS
      PAGE analysis showed an induced expression product band of about 54 kD which
      constituted about 10% of the total bacterial proteins. The analysis of product
      solubility revealed that His(6)-NMT was predominantly soluble. On the basis of
      these results, His(6)-NMT was purified in one-step to 95% of purity from
      bacterial lysates using immobilized metal (Ni(2+)) chelation affinity
      chromatography. The in vitro labelling experiment demonstrated that His(6)-NMT
      had an activity similar to that of mature NMT, suggesting that the His(6)-tag did
      not affect the enzyme activity. His(6)-tag in the N-terminal of NMT makes it be
      possible to immobilized simply on Ni(2+)-IDA Sepharose 6B resin, which can be
      used to screen the peptide inhibitors of NMT from Phage Display random peptide
      library.

PMID- 12215805
TI  - The Role of Different Components of Oxidized LDL in the Inhibition of Nitric
      Oxide Production in Macrophages.
AB  - The role of different components of oxidized LDL (Ox-LDL) in the inhibition of
      LPS-induced nitric oxide (NO) production in macrophages was studied by measuring
      nitrite in the media. The results showed that Ox-LDL was effective, but the
      native and the acetylated LDL were not. The removal of the lipid hydroperoxides
      in Ox-LDL by glutathione peroxidase mimic-ebselen had no effect on the
      inhibition. The protein moiety of Ox-LDL had no effect on NO production, but the
      lipid moiety was inhibitory. Linoleic acid and phosphatidylcholine, the main
      components of LDL lipid, oxidized either separately or together, had no effect on
      NO production, but if linoleic acid was oxidized together with cholesterol there
      was strong inhibition on NO production. Cholesterol oxidized alone also had some
      inhibitory effect. These results suggested that the oxycholesterols in Ox-LDL
      might be responsible for the inhibition of NO production in macrophages.

PMID- 12215806
TI  - Sequencing of Lipoprotein Lipase Gene in 11 Cases of Chinese Patients with Severe
      Endogenous Hypertriglyceridemia.
AB  - Sequencing analysis of lipoprotein lipase (LPL) gene exons l-9 was made in 11
      cases of Chinese patients with severe endogenous hypertriglyceridemia (serum TG >
      7.68 mmol/L) by the dideoxy chain termination method using Sequenase PCR Product
      Sequencing Kit. Four of the patients were found to possess 3 variants at the LPL
      gene locus. One novel mutation was observed at exon 8 Thr(361)-Thr (C(1338)-A).
      This was a conservative mutation with an allele frequency of 1l.4% in the 74 of
      the Chinese controls. Two others Ala(261)-Thr (G(1037)-A) in exon 6 and Ser(447)
      Ter (C(1595)-G) in exon 9, which were also found in Caucasians and have been
      reported to have disease associations with dyslipidaemia, showed at frequencies
      of 0% and 10.7% in the Chinese controls respectively. However, it is the first
      time that these three genetic variants have been reported in Chinese subjects.
      The results show that the gene variation of LPL may not be associated with
      endogenous hypertriglyceridemia in Chinese population.

PMID- 12215807
TI  - Studies on the beta(l-4)Galactosyltransferase of Cell Surface in Induced HL60
      Cells.
AB  - A fluorescene assay method for beta(1-4) galactosyltransferase (beta1-4GT) of
      cell surface has been developed using a pyridylaminated sugar as an acceptor
      substrate. A fluorescent sugar chain, whose reducing end of the Gnbeta1-2Malpha1
      6(Gnbeta1-2Malpha1-3) Mbeta1-4Gnbeta1-4(Fucalpha1-6) Gn has been aminated with 2
      aminopyridine. beta1-4GT activity of cell surface varied in different stages of
      the cell cycle with the highest activity at interphase. The enzyme activity of
      cell surface took a change when HL60 cell line was induced to differentiate by
      PMA or RA. The cell surface enzyme activity was 1.30 times as much as tile
      control group at 24 h in the case of PMA induction, and a maximum increase of 70%
      over the control on the third day with RA induction.

PMID- 12215808
TI  - Characterization and Identification of Recombinant [B18Ile] Human Insulin.
AB  - Recombinant [B18Ile] human insulin was obtained from a mutant [B18Ile] PIP
      purified by transpeptidation. [B18Ile] human insulin can be crystallized and has
      82% of receptor binding activity as that of porcine insulin and retains almost
      the same level of in vivo biological activity comparing with porcine insulin. It
      is proposed that the B18Val residue may not be involved in the expression of
      insulin activity.

PMID- 12215809
TI  - Expression and Activity of Recombinant Human Augmenter of Liver Regeneration.
AB  - The cDNA of human augmenter of liver regeneration was subcloned onto the
      downstream of the P(R)P(L) promoter of the expression plasmid pBV220. The
      recombinant plasmid could stably express ALR with high efficiency (up to 20% of
      the total bacterial proteins) in E. coli through thermal induction. The expressed
      recombinant ALRs could produce a significant increase in the incorporation of
      (3)H-TdR into liver DNA of a 1/3 hepatectomized test animal and also had a potent
      antihepatitis effect. These results suggest that ALR appears to be an important
      regulator of liver regeneration and may be used in clinical trial for enhancing
      liver regeneration in the treatment of hepatic diseases.

PMID- 12215810
TI  - Eukaryotic Expression in COS7 Cells and Biological Activity of Human Brain
      derived Neurotrophic Factor (BDNF).
AB  - In order to study the expression of human brain-derived neurotrophic factor in
      eukaryotic cells, hBDNF cDNA was cut off from MI3mpl8-hBDNF plasmid and inserted
      into the eukaryotic expression vector pCMV4. Using lipofectin methods, the
      recombinant expression plasmid pCMV4-hBDNF was transfected into COS7 cells for
      transient expression. RNA slot hybridization analysis and immunocytoreaction
      analysis demonstrated that the BDNF gene can be transcripted and translated in
      COS7 cells. The human rBDNF secreted by transfected COS7 cells can promote the
      development and survival of dopaminergic neurons.

PMID- 12215811
TI  - Diversity of Archaea in hypersaline environments characterized by molecular
      phylogenetic and cultivation studies.
AB  - The diversity of Archaea from three different hypersaline environments was
      analyzed and compared by polymerase chain reaction (PCR)-based molecular
      phylogenetic techniques and cultivation approaches. The samples originated from a
      crystallization pond of a solar saltern in Spain (FC); an alkaline lake in
      Nevada, USA, (EMF); and a small pond from a slag heap of a potassium mine in
      Germany (DIE). Except for two 16S rDNA sequences that were related to
      crenarchaeota from soil and did not apparently belong to the indigenous
      halophilic community, all sequences recovered from environmental DNA or
      cultivated strains grouped within the Halobacteriaceae. Mostly 16S rDNA sequences
      related to the genera Halorubrum and Haloarcula were detected in sample FC, and
      organisms belonging to these genera were also recovered by cultivation. In
      contrast, sequences related to five different groups of halophilic archaea were
      amplified from sample DIE (including novel lineages with only uncultivated
      phylotypes), but the organisms that were cultivated from this sample fell into
      different groups (i.e., Natronococcus, Halorubrum, or unaffiliated) and did not
      overlap with those predicted using the culture-independent approach. With respect
      to the highly alkaline sample, EMF, four groups were predicted from the
      environmental 16S rDNA sequences, two of which ( Natronomonas and Haloarcula)
      were also recovered through cultivation together with Natronococcus isolates. In
      summary, we found that halophilic archaea dominate the archaeal populations in
      these three hypersaline environments and show that culturability of the organisms
      predicted by molecular surveys might strongly depend on the habitat chosen. While
      a number of novel halophilic archaea have been isolated, we have not been able to
      cultivate representatives of the new lineages that were detected in this and
      several other environmental studies.

PMID- 12215812
TI  - L-aspartate oxidase is present in the anaerobic hyperthermophilic archaeon
      Pyrococcus horikoshii OT-3: characteristics and role in the de novo biosynthesis
      of nicotinamide adenine dinucleotide proposed by genome sequencing.
AB  - A gene encoding the L-aspartate oxidase homologue was identified via genome
      sequencing in the anaerobic hyperthermophilic archaeon Pyrococcus horikoshii OT
      3. We succeeded in expressing the encoding gene in Escherichia coli and purified
      the product to homogeneity. Characterization of the protein revealed that it is
      the most thermostable L-aspartate oxidase detected so far. In addition to the
      oxidase activity, the enzyme catalyzed L-aspartate dehydrogenation in the
      presence of an artificial electron acceptor such as phenazine methosulfate, 2,6
      dichlorophenol-indophenol, and ferricyanide. L-Aspartate oxidase is known to
      function as the first enzyme in the de novo NAD biosynthetic pathway in
      prokaryotes. By a similarity search in public databases, the genes that encode
      the homologue of all other enzymes involved in the pathway were identified in the
      P. horikoshii OT-3 genome. This suggests that P. horikoshii OT-3 may use the de
      novo NAD biosynthetic pathway under anaerobic conditions.

PMID- 12215813
TI  - Cloning, expression, and characterization of the gsdA gene encoding thermophilic
      glucose-6-phosphate dehydrogenase from Aquifex aeolicus.
AB  - The gsdA gene of the extreme thermophilic bacterium Aquifex aeolicus, encoding
      glucose-6-phosphate dehydrogenase (G6PDH), was cloned into a high-expression
      vector and overexpressed as a fusion protein in Escherichia coli. Here we report
      the characterization of this recombinant thermostable G6PDH. G6PDH was purified
      to homogeneity by heat precipitation followed by immobilized metal affinity
      chromatography on a nickel-chelate column. The data obtained indicate that the
      enzyme is a homodimer with a subunit molecular weight of 55 kDa. G6PDH followed
      Michaelis-Menten kinetics with a K(M) of 63 micro M for glucose-6-phosphate at 70
      degrees C with NADP as the cofactor. The enzyme exhibited dual coenzyme
      specificity, although it showed a preference in terms of k(cat)/ K(M) of 20.4
      fold for NADP over NAD at 40 degrees C and 5.7-fold at 70 degrees C. The enzyme
      showed optimum catalytic activity at 90 degrees C. Modeling of the dimer
      interface suggested the presence of cysteine residues that may form disulfide
      bonds between the two subunits, thereby preserving the oligomeric integrity of
      the enzyme. Interestingly, addition of dithiothreitol or mercaptoethanol did not
      affect the activity of the enzyme. With a half-life of 24 h at 90 degrees C and
      12 h at 100 degrees C, this is the most thermostable G6PDH described.

PMID- 12215814
TI  - Cloning and transcriptional analysis of the Thermoanaerobacter ethanolicus strain
      39E maltose ABC transport system.
AB  - Thermoanaerobacter ethanolicus strain 39E is a Gram-positive thermophile that
      converts sugars resulting from plant carbohydrate polymer degradation into
      ethanol. A putative maltose ATP-binding cassette (ABC) transport operon was
      isolated with genes encoding for the integral membrane components (malF and
      malG); the ATP-binding protein (malK); and a partial gene for the maltose-binding
      protein (malE). This operon is unlike most other maltose transport operons, which
      do not contain a contiguous malK gene. Sequence analysis showed that the
      individual genes in the putative operon possessed a considerable range of
      similarities to their respective homologs in other eubacteria and archaea. MalK
      had 52% amino-acid identity and over 70% similarity with its homolog from the
      archaeon Thermococcus litoralis, while the membrane components and binding
      protein exhibited much less similarity with a range of other thermophilic
      eubacteria. Transcript was not detected in maltose-, glucose-, or xylose-grown
      cells using Northern blotting, but RT-PCR showed that malFGK were expressed in
      cells grown on maltose or xylose. Based on these results, the strain 39E maltose
      operon may be subject to glucose catabolite repression.

PMID- 12215815
TI  - Isolation of a novel Thermus thermophilus metal efflux protein that improves
      Escherichia coli growth under stress conditions.
AB  - The mechanisms of metal ion transport in thermophilic organisms are poorly
      understood. Phage display-based screening of a Thermus thermophilus genomic
      library in Escherichia coli led to the identification of a novel metal cation
      efflux protein. The Thermus protein showed extensive sequence and putative
      structural conservation to Czr and Czc proteins in mesophilic bacterial and
      mammalian species. Expression of the gene in E. coli led to increased resistance
      to zinc and cadmium ions, but not to cobalt, in an effect that was apparently
      caused by increased efflux of metals from the cell. This increased resistance was
      inducible by zinc and cadmium and, to a lesser extent, by cobalt. Furthermore, E.
      coli cells containing the Thermus gene exhibited improved cell physiology and
      delayed cell lysis during recombinant protein production, leading to accumulation
      of higher levels of recombinant protein. The molecular basis and potential
      application of the findings are discussed.

PMID- 12215816
TI  - New isolates and physiological properties of the Aquificales and description of
      Thermocrinis albus sp. nov.
AB  - The ecology of the Aquificales was studied using a combination of phylogenetic
      and cultivation approaches. Enrichment cultures were prepared from low-salt and
      marine samples of geothermally and volcanically heated environments of the United
      States (Yellowstone National Park), Russia (Kamchatka), Italy, Germany, Djibouti,
      Iceland, and Africa (Lake Tanganyika). Isolation of single cells using the
      selected cell cultivation technique resulted in 15 different pure cultures.
      Comparisons of their 16S rRNA gene sequences showed that most of the isolates
      were new representatives of the major lineages of the Aquificaceae, represented
      by the genera Aquifex, Thermocrinis, Hydrogenobaculum, and Hydrogenobacter.
      Isolate HI 11/12, which was obtained from whitish streamers in the Hveragerthi
      area of Iceland, represents a separate branch within the Aquificaceae. The
      organism grew at salinities up to 0.7% NaCl and at temperatures up to 89 degrees
      C. Depending on the culture conditions, the organisms occurred as single motile
      rods, as aggregates, or as long filaments that formed whitish streamer-like cell
      masses. The novel isolate grew chemolithoautotrophically with hydrogen, sulfur,
      or thiosulfate as the electron donor under microaerophilic conditions. It
      represents a second species within the order Thermocrinis, which we name
      Thermocrinis albus HI 11/12 (DSM 14484, JCM 11386).

PMID- 12215817
TI  - Biodegradation of high-concentration isopropanol by a solvent-tolerant
      thermophile, Bacillus pallidus.
AB  - The aerobic biodegradation of high-concentration, to 24 g l(-1), 2-propanol (IPA)
      by a thermophilic isolate ST3, identified as Bacillus pallidus, was successfully
      carried out for the first time. This solvent-tolerant B. pallidus utilized IPA as
      the sole carbon source within a minimal salts medium. Cultivation was carried out
      in 100-ml shake flasks at 60 degrees C and compared with cultivation within a 1-l
      stirred tank reactor (STR). Specific growth rate (micro) was about 0.2 h(-1) for
      both systems, with a maximum cell density of 2.4 x 10(8) cells ml(-1) obtained
      with STR cultivation. During exponential growth and stationary phase, IPA
      biodegradation rates were found to be 0.14 and 0.02 g l(-1) h(-1), respectively,
      in shake-flask experiments, whereas corresponding values of 0.09 and 0.018 g l(
      1) h(-1) were achievable in the STR. Generation of acetone, the major
      intermediate in aerobic IPA biodegradation, was also monitored as an indicator of
      microbial IPA utilization. Acetone levels reached a maximum of 2.2-2.3 g l(-1)
      after 72 and 58 h for 100-ml and 1-l systems, respectively. Both IPA and acetone
      were completely removed from the medium following 160 and 175 h, respectively,
      during STR growth, although this was not demonstrated within shake-flask
      reactions. Growth of B. pallidus on acetone or IPA alone demonstrated that the
      maximum growth rate ( micro ) obtainable was 0.247 h(-1) at 4 g l(-1) acetone and
      0.202 h(-1) at 8 g l(-1) IPA within shake-flask cultivation. These results
      indicate the potential of the solvent-tolerant thermophile B. pallidus ST3 in the
      bioremediation of hot solvent-containing industrial waste streams.

PMID- 12215818
TI  - Modification of the enantioselectivity of two homologous thermophilic
      carboxylesterases from Alicyclobacillus acidocaldarius and Archaeoglobus fulgidus
      by random mutagenesis and screening.
AB  - The esterase genes est2 from Alicyclobacillus acidocaldarius and AF1716 from
      Archaeoglobus fulgidus were subjected to error-prone PCR in an effort to increase
      the low enantioselectivity of the corresponding enzymes EST2 and AFEST,
      respectively. The model substrate ( RS)- p-nitrophenyl-2-chloropropionate was
      chosen to produce ( S)-2-chloropropionic acid, an important intermediate in the
      synthesis of some optically pure compounds, such as the herbicide mecoprop. In
      the case of EST2, a single mutant, Leu212Pro, was obtained showing a slightly
      enhanced preference toward the ( S) substrate; in the case of AFEST, a double
      mutant, Leu101Ile/Asp117Gly, was obtained showing an increased preference in the
      opposite direction. The 3-D structures of the EST2 and AFEST enzymes were
      analyzed by molecular modeling to determine the effects of the mutations.
      Mutations were positioned differently in the structures, but in both cases caused
      small modifications around the active site and in the oxyanion loop.

PMID- 12215819
TI  - Identification of thermoacidophilic bacteria and a new Alicyclobacillus genomic
      species isolated from acidic environments in Japan.
AB  - Sixty strains of thermoacidophilic bacteria have been isolated from soil and
      water samples obtained from various acidic environments in Japan. An initial
      comparative sequence analysis of the hypervariable regions of the 16S rDNA
      revealed that all strains could be assigned to the Alicyclobacillus
      acidocaldarius- Alicyclobacillus genomic species 1 group, which could be further
      subdivided into three clusters (Clusters I-III). On the basis of phenotypic
      characteristics, chemotaxonomic profiles, and phylogenetic data of six selected
      strains, five strains were identified as either A. acidocaldarius or
      Alicyclobacillus genomic species 1; however, one strain (MIH 332) could not be
      determined to belong to either of these species. 16S rDNA sequence homology
      values between strain MIH 332 and the reference strains of A. acidocaldarius
      (ATCC 27009(T)) and Alicyclobacillus genomic species 1 (DSM 11984) were 98.8% and
      99.1%, respectively, which were higher than the corresponding similarity between
      the reference strains (98.4%). On the other hand, DNA-DNA hybridization levels
      between strain MIH 332 and the reference strains were 39% and 44%, respectively,
      which were lower than the value between the reference strains (59% or 65%).
      However, the phenotype of strain MIH 332 was also similar to those of the
      reference strains, and a typical phenotype could not be found for the strain,
      thus indicating that the strain may be a new genomic species of A.
      acidocaldarius, for which the name Alicyclobacillus genomic species 2 is
      tentatively proposed. The results of this study suggest that A. acidocaldarius
      and its related species are widely distributed in acidic environments in Japan,
      with slight regional variations in morphological and genotypic characteristics.

PMID- 12215820
TI  - Trehalose production at high temperature exploiting an immobilized cell
      bioreactor.
AB  - The enzymatic production of trehalose from dextrins was studied as a series
      reaction in a packed bed reactor containing immobilized recombinant Escherichia
      coli cells, expressing either the Sulfolobus solfataricus (strain MT4) trehalosyl
      dextrin forming enzyme (TDFE) or the trehalose-forming enzyme (TFE). The cells,
      subjected to thermal treatments to increase cell permeability and to inactivate
      the unwanted host proteins, were entrapped separately or together in a calcium
      alginate polymeric matrix. The biocatalyst beads were used to pack a tubular
      glass reactor that was operated in a recycle mode. The performances of a
      bioreactor containing alternate layers of EcTFE and EcTDFE alginate beads were
      evaluated and compared with the performance of the co-immobilized biocatalysts.
      The latter showed a superior throughput, therefore the bioreactor packed with the
      co-entrapped biocatalysts was tested for the production of trehalose from
      concentrated dextrin solutions (10%-30% w/v) and a conversion up to 90% was
      obtained. This conversion corresponded to a production of 127 g trehalose h(-1)
      kg(-1) of biocatalyst. The results obtained suggest that the bioprocess described
      may be of interest in the development of a large-scale industrial process for
      trehalose production at high temperature.

PMID- 12215821
TI  - Comment on "The first description of an archaeal hemicellulase: the xylanase from
      Thermococcus zilligii strain AN1": evidence that the unique N-terminal sequence
      proposed comes from a maltodextrin phosphorylase.
AB  - Uhl and Daniel reported in this journal in 1999 (Extremophiles 3:263-267) the
      characterization of the first archaeal hemicellulase with a unique N-terminal
      sequence showing no homology with any xylanase or other protein from the
      databases. A genomic library of the chromosomal DNA of Thermococcus zilligii
      strain AN1 was screened by using a degenerate probe deduced from the N-terminal
      sequence. A positive clone was identified, and an amino acid sequence analysis
      revealed that the N-terminal sequence from this protein and the N-terminal
      sequence from the putative xylanase of T. zilligii were identical. However, the
      comparison of the amino acid sequence of the protein with sequences in the main
      protein databases revealed significant similarities with maltodextrin
      phosphorylases. In conclusion, it is likely that the N-terminal sequence proposed
      by Uhl and Daniel is not that of the T. zilligii xylanase, but corresponds to an
      archaeal T. zilligii maltodextrin phosphorylase.

PMID- 12215822
TI  - Nail-patella syndrome. Overview on clinical and molecular findings.
AB  - Nail-patella syndrome (NPS) is a rare autosomal dominant pleiotropic disorder
      characterized by dysplasia of the nails, patellar aplasia or hypoplasia, iliac
      horns, dysplasia of the elbows, and frequently glaucoma and progressive
      nephropathy. The recent identification of the causative gene for this syndrome
      has initiated further studies of the phenotype and molecular pathogenesis of
      kidney disease in NPS. The gene underlying NPS, LMX1B, is a LIM-homeodomain
      transcription factor involved in normal patterning of the dorsoventral axis of
      the limb during development and early morphogenesis of the glomerular basement
      membrane. Molecular studies of Lmx1b, combined with genetic and
      immunohistochemical investigation of different alpha chains of type IV collagen
      in the Lmx1b null mice kidney, a mouse model for NPS, have provided evidence that
      Lmx1b is involved in the pathogenesis of NPS glomerulopathy. At present evidence
      for a correlation between the presence and severity of the renal and extrarenal
      anomalies and LMX1B genotype is lacking. This review focuses on the recent
      advances in clinical and molecular genetic studies of NPS.

PMID- 12215823
TI  - Interleukin genetic variants and the risk of renal failure in infants with
      infection.
AB  - Systemic infection is a major risk factor for the development of neonatal acute
      renal failure (ARF). We investigated whether genetic polymorphisms of tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10 genes
      leading to a more intense inflammatory response might predispose very low birth
      weight (VLBW) infants to the development of ARF in severe infection. The medical
      records of 92 VLBW newborns (birth weight under 1,500 g) with systemic infection
      were analyzed. ARF developed in 38 infants during the 1st postnatal week, while
      54 neonates exhibited normal renal function. The variants of TNF-alpha, IL-1beta,
      IL-6, and IL-10 genes were determined from dried blood samples with polymerase
      chain reaction and restriction fragment length polymorphism methods. The allele
      frequencies did not differ in ARF and in non-ARF babies, while the (TNF-alpha /IL
      6) AG/GC or AG/CC haplotypes were more often present in ARF (26% vs. 6%, P<0.01).
      The single presence of TNF-alpha, IL-1beta, IL-6, and IL-10 variants does not
      influence the development of ARF, but the constellation of TNF-alpha and IL-6
      genetic variants is associated with ARF. We hypothesize that the simultaneous
      presence of these polymorphisms might lead to an enhanced inflammatory response
      in the kidneys in babies with infection.

PMID- 12215824
TI  - Hyperhomocysteinemia in children with renal transplants.
AB  - Many studies have demonstrated a strong association between elevated plasma total
      homocysteine (tHcys) levels and vascular disease. The aim of the present study
      was to determine the plasma levels of tHcys in pediatric recipients of renal
      transplants, to establish possible correlations with renal function, lipid
      profile, and folate and vitamin B12 status, and to assess whether the C677T and
      A1298C polymorphisms in the 5, l0-methylenetetrahydrofolate reductase (MTHFR)
      gene were associated with a particular risk. A total of 26 transplanted children
      and adolescents were investigated. tHcys levels were elevated in transplanted
      patients (12.9+/-4.8 micro mol/l) and 73% of these displayed values above the
      97th percentile of healthy children. Plasma tHcys correlated negatively with
      creatinine clearance ( r=-0.58, P<0.001) and plasma vitamin B(12) ( r=-0.40,
      P<0.05) and positively with plasma triglycerides ( r=0.53, P<0.005). No
      significant correlations were found between plasma tHcys level and age, gender,
      time elapsed after transplantation and plasma values of glucose, insulin, folic
      acid, total cholesterol, low-density lipoprotein-cholesterol, high-density
      lipoprotein-cholesterol, apolipoprotein B, and apolipoprotein A-1. Plasma tHcys
      level was clearly increased in 3 patients with a MTHFR 677TT/1298AA genotype. In
      a multiple stepwise regression model plasma creatinine and triglyceride levels
      and MTHFR 677TT/1298 AA genotype accounted for 60% of the observed plasma tHcys
      variability. The MTHFR 677CT/1298 AC genotype was not a significant predictor of
      tHcys plasma levels. We conclude that a moderate degree of hyperhomocysteinemia
      is often present in renal transplant children and that folate supplementation
      must be considered in this population.

PMID- 12215825
TI  - HLA associations with HBV carriage and proteinuria.
AB  - Human leucocyte antigen (HLA) associations have been reported in children with
      hepatitis B virus (HBV) associated membranous nephropathy (MN). In a previous
      study, we found an association with HLA DQB1*0603 in black children with HBVMN.
      To determine whether HLA DQB1*0603 predisposes to HBV carriage and development of
      abnormal proteinuria, we studied 70 family members of 14 children with HBVMN
      positive for HLA DQB1*0603. HBV was determined using third generation ELISA, slot
      blot hybridisation, and nested polymerase chain reaction. HLA class I antigens
      were determined using a two-staged lymphocytotoxic test whereas class II antigen
      typing was done using sequence-specific primers. Abnormal proteinuria was defined
      by a protein/creatinine ratio > or =0.2. Associations of HLA DQB1*0603 with HBV
      carriage and abnormal proteinuria were determined using the mean probability
      ratio (LOD scores). Forty-seven (67%) family members were positive for HBV
      infection. Nineteen (27%) had abnormal range proteinuria. LOD scores in the study
      subjects with DQB1*0603 who were HBV negative versus those with DQB1*0603 who
      were HBV positive was not significant (anti-log sum =2.0559 and average 0.23).
      When a similar calculation was made for abnormal proteinuria, there were no
      significant findings (anti-log sum =3.8587 and average 0.43). This lack of
      association of HLA DQB1*0603 with either HBV carriage or abnormal proteinuria in
      family members suggests that additional factors may play a role in predisposing
      children to chronic HBV carriage and the development of MN. We therefore conclude
      that the main effect of HLA DQB1*0603 that distinguishes family members from
      HBVMN is the degree of proteinuria, which is a reflection of the severity of
      glomerular basement membrane damage in the latter.

PMID- 12215826
TI  - Rapidly progressive, pauci-immune diffuse crescentic glomerulonephritis in an
      infant.
AB  - A Japanese male infant presented with nephrotic syndrome at 41 days. His renal
      function progressively deteriorated, and he died at 4 months of the age. An open
      renal biopsy revealed diffuse crescentic glomerulonephritis (CrGN) without immune
      complex deposition, which is not characteristic of the congenital nephrotic
      syndrome (CNS). Examination for nephrin antigen using rabbit anti-nephrin extra-
      and intracellular site antibodies was positive. These clinical observations
      suggest that the patient had a unique histological variant of CNS. This is the
      first report of rapidly progressive, pauci-immune diffuse CrGN in infancy.

PMID- 12215827
TI  - Intracellular cytokines of peripheral blood lymphocytes in nephrotic syndrome.
AB  - Idiopathic nephrotic syndrome (NS) is probably caused by abnormalities in T
      lymphocyte function. The presence of several immunological abnormalities in these
      patients supports this hypothesis, but to date there is no agreement about
      immunological status and its influence on the course of NS. Thirty-six children
      with NS [19 with first episode (group I) and 17 in remission (>6 months) of NS
      (group II), aged 4-17 years, mean 7.1 years] were included in the study. Nineteen
      age-matched healthy children constituted the control group. Anti-cytokine
      antibodies were used in conjunction with antibodies against cell surface antigens
      to study cytokine synthesis in different lymphocyte populations. In the present
      study the intracellular synthesis of interleukin-2 (IL-2), interferon-gamma (IFN
      gamma), IL-4, and IL-6 was measured. The intracellular synthesis of IL-2 was
      higher in group I compared with the controls, both in the whole population of T
      lymphocytes (12.1+/-6.2% vs. 7.6+/-6.7%, P=0.0281) and in the subpopulation of
      CD8- lymphocytes (17.3+/-8.5% vs. 7.2+/-4.8%, P=0.0001). No significant
      differences in IFN-gamma intracellular expression were found. The intracellular
      synthesis of IL-4 was lower in group I compared with the controls, both in the
      whole population of T-lymphocytes (1.98+/-1.92% vs. 3.6+/-3.3%, P=0.012) and in
      the subpopulation of CD8- lymphocytes (2.4+/-2.3% vs. 6.5+/-6.4%, P=0.0002).
      Similarly, the intracellular expression of IL-6 was lower in group I compared
      with the control group, in the whole population of T-lymphocytes (0.85+/-0.6% vs.
      2.2+/-3.1%, P=0.004), in the CD8- subpopulation (1.1+/-1.1% vs. 2.2+/-2.0%,
      P=0.006), and in the CD8+ subpopulation (1.1+/-0.9% vs. 2.8+/-3.4%, P=0.0008).
      The results of this study indicate that the acute episode of NS is associated
      with increased intracellular synthesis of IL-2 and decreased intracellular
      synthesis of IL-4 and IL-6.

PMID- 12215829
TI  - Isradipine treatment of hypertension in children: a single-center experience.
AB  - Many children with hypertension, particularly those with new-onset hypertension
      related to glomerulonephritis, organ transplantation, or other forms of secondary
      hypertension, require treatment with a short-acting antihypertensive in order to
      quickly achieve blood pressure (BP) control. We administered isradipine, a short
      acting, second-generation calcium antagonist, to 72 such children. Retrospective
      data collection was undertaken to determine the effects of isradipine treatment.
      The mean age of children treated with isradipine was 74+/-55 months (mean+/-SD).
      Nearly all of these children had secondary hypertension and were initially
      treated as hospital inpatients for newly diagnosed hypertension. Mean isradipine
      dose was 0.36+/-0.17 mg/kg per day, with no significant variation in dose
      according to patient age. Isradipine was administered three times per day in most
      instances, but 21% of the time it was administered four times per day. An
      extemporaneous isradipine suspension was used in 62% of treatment courses. BP
      control was achieved with isradipine alone in 38 children; the remainder received
      isradipine in combination with additional antihypertensives. Comparison of pre
      treatment BP with BP obtained 8+/-9 days later demonstrated a significant BP
      reduction with isradipine treatment, with a mean reduction of 14+/-13 mmHg for
      systolic BP and 13+/-15 mmHg for diastolic BP. There was no effect of isradipine
      treatment on heart rate. Adverse effects occurred in 9.5% of treatment courses,
      and included headache, flushing, dizziness, and tachycardia. We conclude that
      isradipine successfully lowers BP in hypertensive children with secondary forms
      of hypertension. Use of isradipine suspension allows infants and young children
      to be treated as readily as older children.

PMID- 12215828
TI  - Utility of computed tomographic renal angiogram in the management of childhood
      hypertension.
AB  - The purpose of this study was to evaluate the utility of computed tomography (CT)
      renal angiogram (CTRA) in the management of childhood hypertension. This is a
      retrospective study of 24 children with clinical suspicion of renovascular
      disease who underwent CTRA examinations. CTRA demonstrated surgically correctable
      etiology of hypertension in 38% of the patients [5 with renal artery stenosis
      (RAS) and 4 with renal pathology]. In 5 patients, CTRA findings of RAS were
      confirmed by catheter angiogram. CTRA missed RAS in 1 patient in whom catheter
      angiogram showed beaded narrowing of the renal artery. All 6 patients with RAS
      had resolution of hypertension immediately after angioplasty or surgery. One
      patient with diffuse renal artery stenosis had an ipsilateral multicystic
      dysplastic kidney. In this patient hypertension resolved spontaneously as the
      dysplastic kidney shrunk in size. Seven patients had a renal etiology for
      hypertension. In 3 of these patients hypertension resolved after nephrectomy.
      Malignant hypertension in the 4th patient with reflux nephropathy was controlled
      medically after she underwent bilateral ureteral reimplantation. The remaining 3
      patients with renal etiology were managed medically. We found that the etiology
      was central for hypertension in 4 patients with brain abnormalities, obesity in 1
      overweight patient, essential hypertension in 4 patients, and thoracic aorta
      coarctation in 1 patient. Our study showed that in all except 1 instance CTRA
      could diagnose a surgically correctable cause for hypertension. CTRA provided
      useful information for the management of pediatric hypertension in all our
      patients.

PMID- 12215830
TI  - Clinical features in 17 paediatric patients with Wegener granulomatosis.
AB  - The aim of this report was to describe childhood patients with Wegener
      granulomatosis (WG) from one centre, to analyse the variety of clinical
      manifestations seen and compare the data with other published paediatric and
      adult series. The records of 17 patients with WG who were under the care of Great
      Ormond Street Hospital for Children (GOSH) from 1981 to 1998 were reviewed. We
      analysed presenting features before admittance to GOSH and the clinical signs
      observed whilst the children were under the care of the hospital. Of 17 patients,
      13 were females and there was a male/female ratio of 1:3.25. Among the patients
      there were 2 sisters. The age of the patients at disease onset varied from 2
      weeks to 14 years. The median/mean age was 6/6.3 years. American College of
      Rheumatology criteria for diagnosing WG were fulfilled in 11 of 17 patients. The
      frequency of different system involvement was: respiratory 87%, kidneys 53%,
      sinuses 35%, joints 53%, eyes 53%, nervous system 12%, skin 53%. cANCA was
      positive in 10 patients (59%), but pANCA was negative in all measured sera.
      Kidneys were involved in 2 of 8 patients (25%) with the disease onset from 0 to 5
      years and in 7 of 9 patients (78%) with the disease onset from 6 to 14 years (
      P<0.05). cANCA was positive in 7 of 9 patients with kidney disease (78%) and in 2
      of 8 patients (25%) without kidney involvement ( P<0.05). Colchicine as a
      supplement to prednisolone and cytotoxic/immunosuppressant drugs was used
      effectively in 5 patients.

PMID- 12215831
TI  - Henoch-Schonlein nephritis complicated with pulmonary hemorrhage but treated
      successfully.
AB  - Henoch-Schonlein purpura (HSP) is a common vasculitic syndrome in children who,
      in most cases, achieve complete recovery. Occasionally, however, patients develop
      nephritis or nephrotic syndrome with renal failure, or develop significant
      gastrointestinal bleeding. Pulmonary hemorrhage, found mostly in adolescents and
      adults, and with a high mortality rate, has been reported only in a few
      prepubertal children, with a slightly better outcome. A 9-year-old-girl with HSP,
      renal failure, and nephrotic syndrome developed severe bilateral pulmonary
      hemorrhage. After an unsuccessful trial of glucocorticoid therapy, she showed an
      excellent response to cytotoxic therapy.

PMID- 12215832
TI  - Venous pressure monitoring does not accurately predict access failure in
      children.
AB  - Access failure is a significant cause of morbidity and mortality in hemodialysis
      patients. Routine monitoring of arteriovenous (AV) fistulas and grafts could
      increase access longevity. Dynamic venous pressure monitoring is a surveillance
      test advocated to detect early signs of vascular thrombosis. Venous pressure
      measurements obtained, per DOQI recommendations, in children undergoing
      hemodialysis with an AV fistula or graft were reviewed. Baseline venous pressures
      were established by calculating the mean of venous pressures obtained without an
      antecedent thrombosis. A paired t-test was performed comparing mean baseline
      pressure measurements with pressures immediately preceding each thrombosis
      episode. Since some patients had multiple thrombosis episodes, the assumption of
      independence was not met. A second paired t-test was performed comparing mean
      baseline pressures with the mean pressure measurement per individual, obtained
      immediately preceding a thrombosis episode; 335 venous pressures were collected
      in ten pediatric patients. Eighteen thromboses occurred in five patients, in whom
      a total of 241 venous pressures were measured. Venous pressures did not correlate
      with thrombotic events ( P=0.4284). Specific thrombotic events for each patient
      were correlated with mean patient-specific venous pressures and showed no
      correlation ( P=0.3229). Dynamic venous pressure monitoring is not an adequate
      predictor of access thrombosis in pediatric patients.

PMID- 12215833
TI  - Epstein-Barr virus monitoring in paediatric renal transplant recipients.
AB  - Prospective Epstein-Barr virus (EBV) surveillance post transplant was undertaken
      by qualitative polymerase chain reaction testing for EBV DNA in plasma so as to
      detect EBV viremia as early as possible and thereby attempt to pre-empt post
      transplant lymphoproliferative disease by reduction of immunosuppression. Forty
      three children (46 transplants) were followed for a median (range) of 15.5 (3-25)
      months. Thirty-one children (67%) were EBV seropositive pre transplant. Twenty
      children (44%) developed EBV viremia; of these 9 (60%) were seronegative and 11
      (36%) seropositive recipients. Primary infection developed later (median
      difference 14.2 weeks, P=0.009), was more likely to be symptomatic (odds ratio
      2.91, 95% confidence interval 0.95-4.88) and associated with a rise in serum
      creatinine (odds ratio 6.13, 95% confidence interval 4.13-8.13) than reactivation
      disease. There was a higher incidence of EBV disease in children receiving
      quadruple therapy and tacrolimus (odds ratio 13.2, 95% confidence interval 11.5
      14.9) compared with those given cyclosporin-based immunosuppression.
      Immunosuppression was reduced when EBV infection was detected. All children
      became asymptomatic and renal function returned to normal by a median (range) of
      17 (6-52) days, although mild relapses occurred in 3 children. Regular EBV
      surveillance allowed prompt reduction of immunosuppression and was associated
      with a good outcome in this group of children.

PMID- 12215834
TI  - Complex segregation analysis of hypospadias.
AB  - Hypospadias, when the urethra opens on the ventral side of the penis, is a common
      malformation seen in about 3 per 1000 male births. It is considered a complex
      disorder with both genetic and environmental factors involved in the
      pathogenesis. Low birth weight is known to be an important risk factor for
      hypospadias, but several observations speak in favour of genetic factors as well.
      In order to delineate the relative contribution of the genetic factors behind
      hypospadias, we performed a complex segregation analysis of 2005 pedigrees in
      Sweden. The probands were ascertained through the departments of paediatric
      surgery and departments of plastic surgery and urology in Sweden where boys with
      hypospadias undergo surgery. In 7% of the ascertained families one or more
      additional cases of hypospadias were present. The complex segregation analysis
      showed a heritability of 0.99 and evidence for multifactorial inheritance. The
      results suggest that hypospadias might be due to monogenic effects in a small
      proportion of the families, but that there is a multifactorial cause for the
      majority of the cases.

PMID- 12215835
TI  - Gene dosage of the spermidine/spermine N(1)-acetyltransferase ( SSAT) gene with
      putrescine accumulation in a patient with a Xp21.1p22.12 duplication and
      keratosis follicularis spinulosa decalvans (KFSD).
AB  - Keratosis follicularis spinulosa decalvans (KFSD) or Siemens-1 syndrome is a rare
      X-linked disease of unknown etiology affecting the skin and the eye. Although
      most affected families are compatible with X-linked inheritance, KFSD appears to
      be clinically and genetically heterogeneous. So far, the gene has been mapped to
      Xp22.13p22.2 in two extended KFSD families. Analysis of additional recombination
      events in the first Dutch pedigree located the gene to an interval covering
      approximately 1 Mb between markers DXS7163 and DXS7593/DXS7105, whereas haplotype
      reconstruction in the second German family positioned the gene outside the
      previously identified region, proximal to marker DXS274. We report here the
      molecular characterization of an Xp21.1p22.12 duplication present in a patient
      affected with dosage-sensitive sex reversal (DSS) and KFSD. The duplicated region
      includes both the DAX1 gene (previously demonstrated to be responsible for DSS)
      and the KFSD interval, in which the gene encoding spermidine/spermine N(1)
      acetyltransferase ( SSAT) is located. This enzyme catalyzes the N(1)-acetylation
      of spermidine and spermine and, by the successive activity of polyamine oxidase,
      the spermine can be converted to spermidine and the spermidine to putrescine.
      Overexpression of the SSAT enzyme in a mouse model results in putrescine
      accumulation and a phenotype with skin and hair abnormalities reminiscent of
      human KFSD. Analysis of polyamine metabolism in the cells of the patient
      indicated that the levels of metabolites such as putrescine, spermidine and
      spermine were consistent with the overexpression of the SSAT gene as in the
      murine model. Thus, we propose that overexpression of SSAT and the consequent
      putrescine accumulation are involved in the KFSD phenotype, at least in our
      propositus.

PMID- 12215836
TI  - A point mutation, R59G, within the HMG-SRY box in a female 45,X/46,X, psu
      dic(Y)(pter-->q11::q11-->pter).
AB  - We report a molecular and cytogenetic investigation of a psu dic(Yp) chromosome
      identified in blood and ovarian tissue from a female with mosaic karyotype
      45,X/46,X,+ psu dic(Yp). FISH analysis showed that the psu dic(Yp) has two copies
      of the short arm, two centromeres and two copies of the proximal long arm. PCR
      analysis also confirmed the presence of the SRY gene and the Y centromere, and
      also confirmed the deletion of the Y-heterochromatic region. Because of the
      possibility of a mutation, a fragment of 609 bp of the SRY gene was sequenced
      from independent PCR products. The analysis of the sequence indicated the
      presence of two different copies of the gene: one presented a point mutation,
      R59G, within the HMG-box; the other had a sequence identical to that already
      published. Both sequences were found at a proportion of 1:1. The absence of a
      46,XY cell line suggests that the rearrangement took place during gametogenesis
      or during the first division after fertilization. Also, the existence of
      different sequences of the SRYgene in the same Y chromosome suggests that the
      formation of the dicentric took place prior to the mutation of the SRY gene. To
      our knowledge, this is the first time that a mutation has been described in codon
      59 within the HMG- SRY box, and also the first case of a psu dic(Yp) chromosome
      that displays two different copies of the SRY gene.

PMID- 12215837
TI  - Spatial and temporal distribution of cystic fibrosis and of its mutations in
      Brittany, France: a retrospective study from 1960.
AB  - Cystic fibrosis (CF) is the most common severe inherited disorder that affects
      children in Caucasian populations. The aim of this study was to define the
      spatial and temporal distribution of CF and its mutations in Brittany (western
      France) where the frequency of the disease is high. We retrospectively registered
      all CF patients born in Brittany since 1960 by cross-checking various data
      sources (e.g. medical care centres, genetics laboratories, hospital archives).
      Councils were contacted so that the place of residence of patients at birth could
      be determined. Moreover, the spectrum of CF transmembrane conductance regulator
      (CFTR) mutations and their spatial distribution across Brittany were determined.
      A total of 520 patients was registered in this study. The incidence of CF was
      assessed according to administrative (department, district) and diocesan
      divisions of Brittany and its evolution analysed over four decades. The incidence
      of CF was 1/2630, with a west/east gradient that was confirmed over time
      (Finistere: 1/2071 vs Ille-et-Vilaine: 1/3286). At present, the incidence of CF
      is decreasing, mainly as a result of prenatal diagnosis. An excellent mutation
      detection rate of 99.7% was obtained. Western Brittany presented a specific
      spectrum of mutations: 1078delT (9.4% of mutated alleles in the diocese of
      Cornouaille), G551D (7.7% in the diocese of Leon), 4005+1G-->A (2.9% in
      Cornouaille) and W846X (1.5% in western Brittany). On the other hand, the eastern
      region showed a spectrum more similar to the overall picture in France as a
      whole. This study enabled a precise measurement of the incidence of CF in
      Brittany to be obtained. The high frequency of the CFTR mutated alleles may
      result from founder effects and genetic drifts. Moreover, the study brings
      together the regional specificities of the CFTR gene and highlights disparities
      that exist in this part of France, both in incidence and in mutation
      distribution. These are attributable to different degrees of isolation and of
      population movements between the eastern and western parts of the region. Given
      that this is the first time that such a detailed study of the CFTR gene has been
      performed on a large population, this heightened knowledge of the epidemiology of
      CF in Brittany should provide a basis for the improvement of diagnostic
      strategies and refinement of genetic counselling.

PMID- 12215838
TI  - Haplotype study of West European and North African Unverricht-Lundborg
      chromosomes: evidence for a few founder mutations.
AB  - Unverricht-Lundborg disease (ULD) is a progressive myoclonus epilepsy common in
      Finland and North Africa, and less common in Western Europe. ULD is mostly caused
      by expansion of a dodecamer repeat in the cystatin B gene ( CSTB) promoter. We
      performed a haplotype study of ULD chromosomes (ULDc) with the repeat expansion.
      We included 48 West European Caucasian (WEC) and 47 North African (NA) ULDc. We
      analysed eight markers flanking CSTB(GT10-D21S1890-D21S1885-D21S2040-D21S1259-
      CSTB-D21S1912-PFKL-D21S171) and one intragenic variant in the CSTB 3' UTR
      (A2575G). We observed a founder effect in most of the NA ULD patients, as 61.7%
      of the NA ULDc (29/47) shared the same haplotype, A1 (1-1-A-1-6-7), for markers
      D21S1885-D21S2040-A2575G-D21S1259-D21S1912-PFKL. Moreover, if we considered only
      the markers D21S1885, D21S2040, A2575G and D21S1259, 43 of the 47 NA ULDc shared
      the same alleles 1-1-A-1, haplotype A. As previously shown, the WEC ULDc were
      heterogeneous. However, the Baltic haplotype, A3 (5-1-1-A-1-1), was observed in
      ten WEC ULDc (20.8%) and the CSTB 3'UTR variant, which we called the Alps
      variant, was observed in 17 ULDc (35.4%). Finally, as almost all NA patients,
      like Scandinavian patients, were of the haplotype A, we assumed that there was an
      ancient common founder effect in NA and Baltic ULD patients. We estimated that
      the putative most recent common ancestral ULD carrier with this haplotype A must
      have existed about 2,500 years ago (100-150 generations). Finally, this work
      provides evidence for the existence of only a small number of founder mutations
      in ULD.

PMID- 12215839
TI  - A genome-wide screen reveals evidence for a locus on chromosome 11 influencing
      variation in LDL cholesterol in the NHLBI Family Heart Study.
AB  - A genome scan was performed for low-density lipoprotein cholesterol concentration
      (LDL-C) in white subjects who were ascertained through the NHLBI Family Heart
      Study (FHS). The NIH Mammalian Genotyping Service (Marshfield, Wis.) genotyped
      401 autosomal markers spaced at approximate 10-cM intervals. Additional FHS
      families were genotyped by the FHS Molecular Laboratory at the University of Utah
      for 243 markers; 645 subjects were typed in both laboratories so that a combined
      map of the 644 markers from the two screening sets (average distance of 5.46 cM)
      could be produced. Analyses were done on 2,799 genotyped subjects in 500 families
      where at least two genotyped persons in the family had measured LDL-C levels
      (average number of genotyped family members=5.95). The variance components method
      was used as implemented in GeneHunter (Kruglyak et al. 1996). Prior to analysis,
      each phenotype was adjusted, within sex, for age, age squared, body mass index,
      waist-hip ratio, alcohol, smoking, medication status for diabetes and
      hypertension, estrogen use, and field center location. Linkage analyses were
      performed, first excluding 305 subjects on lipid-lowering medications, then again
      including the data from these subjects. The highest peak was on chromosome 11 at
      56.3-56.4 cM, with a maximum lod score of 3.72. Two genome scans of lipid traits
      in other populations have found peaks in this region. Other scores at or above
      1.9 occurred on chromosomes 5 (lod=1.89 at 1.6 cM), 10 (lod=2.47 at 127.1 cM), 17
      (lod=2.33 at 116.3 cM), and 21 (lod=2.74 at 45.2 cM).

PMID- 12215840
TI  - A genome screen for linkage disequilibrium in HLA-DRB1*15-positive Germans with
      multiple sclerosis based on 4666 microsatellite markers.
AB  - Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system
      with putative autoimmune aetiology and complex genetic background. Here, we
      report the results of a genome screen for linkage disequilibrium (LD) by using
      6000 microsatellite markers in 198 HLA-DRB1*15-positive MS patients and 198
      unrelated controls (pooled DNA); 4666 analysed markers could be included in the
      resulting association map, from which 87 revealed significant differences between
      MS cases and controls.

PMID- 12215841
TI  - Molecular analysis in true hermaphroditism: demonstration of low-level hidden
      mosaicism for Y-derived sequences in 46,XX cases.
AB  - True hermaphroditism (TH) is an unusual form of sex reversal, characterized by
      the development of testicular and ovarian tissue in the same subject.
      Approximately 60% of the patients have a 46,XX karyotype, 33% are mosaics with a
      second cell line containing a Y chromosome, while the remaining 7% are 46,XY.
      Molecular analyses have demonstrated that SRY is present in only 10% of TH with a
      46,XX karyotype; therefore, in the remaining 90%, mutations at unknown X-linked
      or autosomal sex determining loci have been proposed as factors responsible for
      testicular development. True hermaphroditism presents considerable genetic
      heterogeneity with several molecular anomalies leading to the dual gonadal
      development as SRY point mutations or SRY hidden gonadal mosaicism. In order to
      identify genetic defects associated with subjects with the disease, we performed
      molecular analyses of the SRY gene in DNA from blood leukocytes and gonadal
      tissue in 12 true hermaphrodites with different karyotypes. Our results using PCR
      and FISH analyses reveal the presence of hidden mosaicism for SRY or other Y
      sequences in some patients with XX true hermaphroditism and confirms that
      mosaicism for SRY limited to the gonads is an alternative mechanism for
      testicular development in 46,XX true hermaphrodites.

PMID- 12215842
TI  - Differential rates of frameshift alterations in four repeat sequences of
      hereditary nonpolyposis colorectal cancer tumors.
AB  - DNA sequences of mono-, di-, and trinucleotide repeats are prone to replication
      errors and thus constitute mutational hot spots. This is well illustrated by the
      occurrence of DNA microsatellite instability in tumors from patients affected by
      hereditary nonpolyposis colorectal cancer (HNPCC) resulting from a defect in a
      gene that participates in postreplicative DNA mismatch repair (MMR). We selected
      repeat sequences present within coding regions of four genes involved in either
      cell proliferation or promotion of apoptosis. These repeats consisted of (A)10 in
      the TGF beta RII, (G)8 in the BAX, (A)8 in the CASP1, and (CCA)7 in the APP
      genes. These repeats were analyzed in ten tumors from HNPCC patients carrying a
      germline pathogenic mutation in the MMR gene MLH1. For each tumor the rate of
      somatic replication errors was measured by sequencing 20-50 cloned PCR-amplified
      fragments. Substantial intertumor variations were observed in the pattern of
      repeat alterations, with error rates varying between 12% and 80% for TGF beta
      RII, 2% and 84% for BAX, 0% and 30% for CASP1, and 0% to 18% for APP. The BAX
      repeat error rate did not exceed 20% in nine of the ten tumors, in contrast to
      results from previous studies. High error rates in more than one gene in a same
      tumor suggested additive selective effects from inactivation of different
      pathways influencing tumorigenesis. Our methodology can contribute to define
      tumor characteristics and may, if applied to genes strongly involved in
      tumorigenesis, improve tumor classification and outcome prediction.

PMID- 12215843
TI  - Duplications of chromosome 11p15 of maternal origin result in a phenotype that
      includes growth retardation.
AB  - Paternal duplications of distal 11p result in Beckwith Wiedemann syndrome (BWS),
      whereas maternal duplications have not, to our knowledge, been reported
      previously in the literature. We present three unrelated patients with maternal
      duplications of distal 11p. Patient 1 is a 31-year-old female with a de novo
      inverted duplication of distal 11p, i.e. inv dup del(11)(qter-->p15.5::p15.5-
      >15.3); this rearrangement was shown to be maternal in origin by microsatellite
      analysis and methylation-specific polymerase chain reaction. Patient 2 is a 4
      year-old female with a derived chromosome 20, which arose from adjacent 1
      malsegregation of a maternal t(11;20)(p15.3;q13.33). Patient 3 presented as an
      intrauterine death with trisomy for the majority of chromosome 11p as a result of
      3:1 segregation of a maternal t(11;15)(p11.2;q11.2). In view of the imprinted
      status of this region, it is pertinent that none of our patients showed features
      of BWS; indeed, all had growth retardation, in contrast to the overgrowth
      characteristic of BWS. It is of note that, of the living patients, Patient 1 went
      into early puberty at 9.5 years and Patient 2 showed breast development in
      infancy. Both patients shared some dysmorphological features, namely short
      palpebral fissures, a prominent nasal tip, a short philtrum and 5th finger
      clinodactyly.

PMID- 12215844
TI  - Favourable mutation test outcomes for individuals at risk for Huntington disease
      change the perspectives of first-degree relatives.
AB  - In mutation testing for Huntington disease, an autosomal dominant hereditary late
      onset disorder, unfavourable test outcomes in at-risk individuals provide
      important information about other family members at risk. On the other hand,
      common counselling practice considers favourable outcomes as non-informative for
      at-risk relatives, except for the offspring of the tested individual. We shall
      show, however, that favourable outcomes also change the perspectives for the
      tested individual's first-degree relatives at risk. In the case of a
      (prospective) parent originally at 50% risk, and with n equalling the number of
      children or fetuses identified as non-carriers, the probability of being a non
      carrier equals 2 (n)/(2 (n)+1) for the at-risk parent, providing that none of the
      offspring of this parent has been identified as a carrier. Likewise, the
      probability of being a non-carrier equals (2 (n+1)+1)/(2 (n+1)+2) for the
      (future) siblings of the tested individual. These changes in probabilities are
      important for individuals who are considering prenatal or presymptomatic DNA
      testing for autosomal dominant hereditary late-onset disorders, such as
      Huntington disease and hereditary forms of cancer (BRCA1/2, FAP, HNPCC).
      Consequences can be far reaching in the case of pregnancies, where the risk of
      miscarriage after a prenatal test is 1%-2%. Parents initially at 50% risk may
      consider not having a prenatal test in successive pregnancies, knowing that
      favourable test results in previous pregnancies have considerably reduced their
      personal risk.

PMID- 12215845
TI  - Thymidylate synthase: a novel genetic determinant of plasma homocysteine and
      folate levels.
AB  - The thymidylate synthase gene ( TYMS or TS) encodes a tightly regulated enzyme
      that catalyzes the conversion of deoxyuridylate to thymidylate, and contains a
      tandem repeat polymorphism that affects expression of the enzyme. We have
      investigated the relationship between TYMS genotype and plasma concentrations of
      homocysteine and folate in a cohort of 505 Chinese from Singapore. TYMS 3/3
      genotype was associated with reduced plasma folate and, among individuals with
      low dietary folate intake, with elevated plasma homocysteine levels. These
      associations were independent of the well-established methylenetetrahydrofolate
      reductase ( MTHFR) C677T genotype effects on plasma folate and homocysteine
      levels. Our results suggest that TYMS and MTHFR compete for limiting supplies of
      folate required for the remethylation of homocysteine. These genetic determinants
      of plasma folate and homocysteine levels may be useful in identifying individuals
      at increased risk for cardiovascular disease.

PMID- 12215846
TI  - Minimally invasive therapies for benign prostatic hyperplasia.
AB  - A number of minimally invasive therapies have been studied in the last decade for
      the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia
      (BPH). Most of these utilize thermal energy to ablate the prostate. Paucity of
      long-term efficacy, safety and re-treatment rates are, however, the main concerns
      of all these forms of treatment. Minimally invasive therapies can be positioned
      between pharmacotherapy and transurethral resection of the prostate (TURP).
      Studies have shown that some of these therapies stand the test of time, with low
      and acceptable re-treatment rates and shorter hospital stay. Therapies such as
      transurethral needle ablation (TUNA) and high energy transurethral microwave
      thermotherapy (HE-TUMT) effectively relieve symptoms with less morbidity. Laser
      prostatectomy is less commonly used due to the slow and difficult
      resection/vaporization. Minimally invasive therapies are particularly useful in
      those on anticoagulants, in whom anesthesia is contraindicated and younger men
      with an active sex life. However, these devices have not been compared with TURP
      in large-scale controlled trials and, therefore, will not be able to replace TURP
      until their long-term durability of symptom relief is known.

PMID- 12215847
TI  - Fundamentals on the pathology of prostatic carcinoma after brachytherapy.
AB  - Morphologic analyses of radical prostatectomy specimens after brachytherapy are
      rarities, as only few patients undergo radical prostatectomy due to prostate
      specific antigen (PSA) progress after brachytherapy. In the literature, there are
      merely sporadic reports that do essentially correspond to findings after
      conventional radiotherapy with regressive changes in the tumor glands and,
      especially, in the surrounding stroma. From the presented cases, it can be
      concluded that the seed density must be very high in order to prevent tumor
      progression through undamaged parts of the carcinoma. The sequels of
      brachytherapy are compared with the reactions of prostatic carcinomas to various
      modes of therapy. It is demonstrated what the clinician can expect and which
      modes of control exist at present.

PMID- 12215848
TI  - Improvement of practice performance in urological surgery via clinical pathway
      implementation.
AB  - The purpose of this study was to compare performance measurements to evaluate the
      effects of clinical pathway implementation on improving practice performances in
      urology. Since April 1997, a total of 18 clinical pathways have been created in
      the urology department. Of these clinical pathways, six were implemented for
      endoscopic surgery, and four and eight were for minor and major surgery,
      respectively. Eight prominent performance measurements, which were identified as
      representative indicators of the practice performances, were selected in
      endoscopic surgery, five in minor surgery, and 11 in major surgery. Between April
      1997 and March 1999, 2,883 consecutive patients, who underwent endoscopic
      surgery, minor surgery, and major surgery, were evaluated herein. The treatment
      results for patients in the first and second years of clinical pathway
      implementation were compared to those from the year preceding the implementation.
      In endoscopic surgery, five of the eight performance measurements improved
      significantly in the first year of implementation. Notably, three of the five
      improved performances continued to improve in the second year. Similarly, in
      minor surgery, four of the five performance measurements improved significantly
      following 2 years. Finally, in major urological surgery, six of the 11
      performance measurements also improved significantly after 1 year; four of which
      continued to improve during the second year. Therefore, we conclude that patient
      care, which is based on the implementation of clinical pathways, can improve
      practice performances and facilitate medical care.

PMID- 12215849
TI  - Retroperitoneal laparoscopic radical nephrectomy and nephroureterectomy and
      comparison with open surgery.
AB  - To compare the efficacy, safety and oncological completeness of
      retroperitoneoscopic radical nephrectomy (RPRN) and nephroureterectomy (RPRNU)
      with that of the open retroperitoneal approach for radical surgery for localised
      renal cell carcinoma and upper tract transitional cell carcinoma. Eighteen
      patients of RPRN, nine of RPRNU, 11 of open radical nephrectomy (ORN) and five
      patients who underwent open radical nephroureterectomy (ORNU) were evaluated. The
      groups were similar to each other. The mean operative times in the laparoscopic
      group were longer (147 and 188.7 min for RPRN and RPRNU vs 127.7 and 184 min for
      ORN and ORNU, respectively); however, the mean analgesic requirement (203.3 and
      275 mg for RPRN and RPRNU vs 400 and 650 mg pethidine for ORN and ORNU,
      respectively), hospital stay (3.2 and 5.1 days for RPRN and RPRNU vs 7.6 and 9.2
      days for ORN and ORNU, respectively) and return to normal activities (2 and 2
      weeks in RPRN and RPRNU vs 4.3 and 4.6 weeks for ORN and ORNU, respectively) were
      lower in the retroperitoneoscopic group. Tumour-free margins could be achieved in
      all the cases. The mean duration of follow-up for RPRN and RPRNU was 17.7 and
      15.0 months and for ORN and ORNU were 32.5 and 19.0 months, respectively. There
      was no port site or local recurrences. Distant metastasis developed in one case
      of RPRN and in two cases of RPRNU. The retroperitoneoscopic approach for a
      localised malignancy of the upper urinary tract appears to be effective and safe.
      An oncologically complete removal of the tumour is possible as in open surgery.
      The retroperitoneoscopic approach is associated with less morbidity and faster
      recovery.

PMID- 12215850
TI  - Nephron-sparing surgery in multiple bilateral angiomyolipomas.
AB  - We report on a 17-year-old white woman with multiple bilateral renal
      angiomyolipomas (AMLs) in the absence of tuberous sclerosis. Multiple hyperdense
      lesions were detected in both kidneys by sonography. A computed tomography (CT)
      scan confirmed mainly fatty tissue. Sparing as much functional tissue as
      possible, eight AMLs of the right kidney were resected. The largest removed
      tumour measured 7 x 4 x 2.4 cm. Renal function was completely preserved. An AML
      is a benign, generally unilateral renal tumour. Treatment is necessary in cases
      of flank pain, spontaneous bleeding, obstruction by tumour growth and tumours
      exceeding 4 cm in diameter. Patients who present are often symptomatic due to
      pain, retroperitoneal bleeding or haematuria. An AML occurs either sporadically
      or in association with tuberous sclerosis. Bilateral or unilateral multiple AMLs
      are rare.

PMID- 12215851
TI  - The impact of extracorporal circulation on therapy-related mortality and long
      term survival of patients with renal cell cancer and intracaval neoplastic
      extension.
AB  - In approximately 4%-10% of patients presenting with renal cell cancer, the
      transluminal propagation of a tumour thrombus into the vena cava inferior or the
      right atrium comes to diagnosis. Recent investigations have indicated that the
      presence of neoplastic extension into the venous system does not reveal
      independent prognostic value regarding the clinical course of the disease.
      Although the complete surgical removal of vena cava thrombosis in patients
      without simultaneously occurring regional lymph node or distant metastases has
      become a well established treatment modality, several questions concerning this
      surgical strategy still remain the subject of ongoing discussions. In the present
      investigation that included 92 patients with renal cell cancer and intracaval
      neoplastic extension, it was clearly demonstrated that using cardiopulmonary
      bypass, deep hypothermia and circulatory arrest - preferably, during the removal
      of intracaval thrombosis extending into the right atrium - does not result in a
      substantially increased treatment-related intra- or postoperative mortality.
      However, in contrast to a previously reported observation, this treatment option
      did not reveal any substantial impact on the long-term survival of the patients
      following surgical therapy. Accordingly, the cranial extension of intracaval
      thrombosis was not identified as a biological variable of any prognostic
      importance for renal cell cancer patients.

PMID- 12215852
TI  - Retroperitoneal schwannoma mimicking an adrenal lesion.
AB  - Schwannomas are usually benign tumors that arise from the nerve supporting the
      Schwann cell. The majority arise at the cranial nerves or nerves of the upper
      extremities. Most patients with retroperitoneal schwannomas present with vague
      abdominal or back pain. We present a case in which a retroperitoneal mass thought
      to be arising from the adrenal gland on computed tomography and magnetic
      resonance imaging was found after excision to be a Schwannoma. The available
      literature on retroperitoneal schwannomas is then discussed.

PMID- 12215853
TI  - Surgical treatment for stress urinary incontinence with urethral hypermobility:
      what is the best approach?
AB  - A comparative study evaluating the results of three surgical procedures for
      stress urinary incontinence (SUI) with urethral hypermobility. This is a
      retrospective study of 189 patients, evaluating the outcomes of the percutaneous
      needle suspension using bone anchors (PNS), abdominal suspension (AS), and
      pubovaginal sling (PVS). The mean follow-up was 30.5 months. In our results, the
      patients were divided into three groups: PNS (49), AS (34), and PVS (106). No
      differences were found preoperatively. Intraoperatively, PNS had the shortest
      operative time and lowest estimated blood loss, and it is the only outpatient
      procedure. However, it had the highest complication rate. PNS had the lowest
      satisfactory rate (16.7%). This was followed by AS (78%), PVS with cadaveric
      fascia (90%), and PVS with autologous fascia (94%). In conclusion, PNS is a
      simple outpatient procedure, but the long-term results are disappointing. Both AS
      and PVS gave good results. PVS was superior to AS in shorter hospitalization,
      early recovery and overall patient satisfaction.

PMID- 12215854
TI  - Electrified urinary drainage bag: an in vitro study.
AB  - An experimental study was designed to examine the effect of electrical current on
      bacteria-contaminating urinary drainage bags. An experimental model analogous to
      a urinary drainage system has been formed. Bottles containing 1,000 ml urine
      inoculated with Pseudomonas aeruginosa, Klebsiella pneumoniae or Escherichia coli
      in different experimental settings were drained with constant speed into urinary
      drainage bags in which platinum electrodes had been implanted. An experimental
      procedure involved applying an electrical current with a 12 V DC generator into
      bags containing urine for 24 h. Cultures were obtained separately from the bags
      and microorganism-inoculated bottles for 24 h and following a cessation of
      electrical current for another 24 h. In electrified bags, P. aeruginosa was
      killed in all experiments. E. coli and K. pneumoniae were eradicated at the end
      of 24 h. However, K. pneumoniae began to grow in increasing numbers following the
      cessation of the electrical current. An electrical current might decrease or
      eradicate the bacteria in urinary-drainage bags. This might be one of the ways to
      decrease the risk of in vivo cross-contamination and nosocomial infections.

PMID- 12215855
TI  - Possible role of bioactive peptides in the regulation of human detrusor smooth
      muscle - functional effects in vitro and immunohistochemical presence.
AB  - Results from basic research implicate a role for bioactive peptides in
      controlling the mammalian lower urinary tract. Although various peptides are
      assumed to be involved in the potentiaton or inhibition of cholinergic or
      purinergic activity in the urinary bladder, there is still much controversy
      regarding the mode of action and functional significance of such peptides in
      detrusor smooth muscle. Thus, we evaluated the functional effects of atrial
      natriuretic peptide (ANP), calcitonin gene related peptide (CGRP), endothelin 1
      (ET-1), substance P (SP) and vasoactive intestinal polypeptide (VIP) on isolated
      strip preparations of human detrusor smooth muscle and determined the presence of
      those peptides in the human detrusor by means of immunohistochemistry. The
      effects of peptides on isometric tension of isolated detrusor strip preparations
      and on tissue levels of cyclic nucleotides cAMP and cGMP were compared to those
      of adenylyl cyclase activator forskolin (F), nitric oxide donor Na(+)
      nitroprusside (SNP) and non-specific phosphodiesterase (PDE) inhibitor papaverine
      (P). The effects of the compounds on isometric tension of isolated human detrusor
      smooth muscle were examined using the organ bath technique. To determine time-
      and dose-dependent effects on cyclic nucleotide levels, bladder strips were
      exposed to increasing doses of F, SNP, P, ANP, CGRP and VIP, then rapidly frozen
      in liquid nitrogen and homogenised in the frozen state. cAMP and cGMP were
      extracted and assayed using specific radioimmunoassays. The presence of peptides
      was investigated by light microscopy using the Avidin-Biotin-Complex (ABC)
      method. F, P and VIP most effectively reversed the carbachol-induced tension of
      isolated human detrusor strips. Relaxing effects of ANP, CGRP and SNP were
      negligible. In contrast, ET-1 and SP elicited dose-dependent contractions of the
      tissue. The relaxing effects of F, P and VIP were accompanied by an increase in
      cAMP and cGMP levels, respectively. Light microscopy revealed positive
      immunostaining for CGRP, ET 1, VIP and SP in sections of the detrusor muscle
      coat. Our results suggest a possible importance of ET 1, SP and VIP in regulating
      detrusor smooth muscle contraction and relaxation. Even if a peptide is not
      synthesised, stored or released in a smooth muscle tissue and is, therefore,
      unable to reach its target cells under physiologic conditions, a functional
      effect on the tissue might be mediated by peptide-binding to specific cell
      surface receptors.

PMID- 12215856
TI  - Smooth muscle cells from human urinary bladder express connexin 43 in vivo and in
      vitro.
AB  - Smooth muscle cells (SMC) of the human urinary bladder are believed to be
      electrically coupled. However, it has not been successfully demonstrated the
      nature of the underlying cell-cell communication. Here, we used Western blot
      technique to demonstrate the gap junction protein connexin 43 (Cx 43) in human
      bladder musculature and in smooth muscle cell cultures. We found expression of Cx
      43 in all samples of the detrusor (Mdv, n=6) and in five of six samples of the
      internal sphincter (Mv). Cx 43 expression was less in cell cultures, 60% showing
      Cx 43 expression. Iontophoretic application of the gap junction permeable
      fluorescent dye lucifer yellow revealed a mean of 2.6+/-2.2 (mean+/-SD, n=8)
      coupled cells in cultured smooth muscle cells. Our findings support the notion
      that Cx 43 is constitutively expressed in human bladder SMC in vivo. Thus, the
      function of the bladder is likely to be influenced by the organisation of smooth
      muscle cells into functional syncytia.

PMID- 12215857
TI  - Cloning of COX4 cDNA from the NZ white rabbit and expression of this gene in
      bladder smooth muscle following partial outlet obstruction.
AB  - We cloned and characterized the rabbit COX4 coding sequence, then examined
      expression of the gene in bladder smooth muscle following partial obstruction of
      the bladder outlet. Obstruction was done surgically in male NZ white rabbits and
      bladders procured at 1, 3, 5, 7, and 14 days post-obstruction (two animals/time).
      RNA, then cDNA, was prepared from smooth muscle from each sample. Cloning was
      done from cDNA by PCR. COX4 mRNA in smooth muscle was defined by real-time RT
      PCR, using cDNA from bladder samples. The rabbit COX4 coding sequence specifies a
      protein of 169 amino acids, including a membrane transit sequence for
      mitochondrial (mt) entry. Expression of COX4 in bladder smooth muscle decreased
      by 80% in the first day post-obstruction and remained low through 14 days post
      obstruction. Cytochrome oxidase activity decreased sharply in the first 3 days
      post-obstruction in smooth muscle, in concert with COX4 transcript levels.
      Partial outlet obstruction of the rabbit urinary bladder results in attenuation
      in smooth muscle of mRNA synthesis from the COX4 gene. In turn, this results in
      attenuated activity of mt electron transport due to limited availability of
      nucleus-encoded components required for the assembly of cytochrome oxidase.

PMID- 12215858
TI  - Homologous acellular matrix graft for vaginal repair in rats: a pilot study for a
      new reconstructive approach.
AB  - The purpose of this paper is to investigate using an acellular matrix graft of
      vagina (VAMG) or bladder (BAMG) in vaginal reconstruction. In 18 rats, vaginal
      length was measured and a hysterectomy performed. In three control animals, the
      vaginal stump was closed. In eight rats, the vagina was augmented with a VAMG; in
      seven, a BAMG was used. After 2-12 weeks, the animals were sacrificed, the
      vaginal length was reevaluated, and the vaginas were prepared for histologic
      evaluation. In the controls, the vagina was markedly shorter postoperatively. In
      the grafted animals, vaginal length was not significantly less than preoperative
      values with either matrix. Epithelialization, vascularization, and alpha-actin
      expression in the grafts were consistently observed. Regeneration appeared to be
      slightly greater in the organ-specific vagina matrix. With either matrix,
      however, although the vaginal stump remained open, the grafts lost most of the
      lumen. Vaginal reconstruction with a vagina acellular matrix graft is technically
      feasible. If further experiments can address the problem of luminal collapse -
      with, for instance, tissue expanders in the matrix - this technique may offer an
      alternative to the complex therapeutic options currently available.

PMID- 12215859
TI  - The protective role of caffeic acid phenethyl ester (CAPE) on testicular tissue
      after testicular torsion and detorsion.
AB  - Testicular artery occlusion causes an enhanced formation of reactive oxygen
      species, which contributes to the pathophysiology of tissue damage. Here, we have
      investigated the effects of caffeic acid phenethyl ester (CAPE), a new
      antioxidant and antiinflammatory agent, in rats subjected to testicular
      torsion/detorsion (T/D). Thirty-five male rats were divided into four groups:
      sham operation group ( n=8), torsion group ( n=9), T/D+saline group ( n=9) and
      T/D+CAPE group ( n=9). Rats, except the sham operation group, were subjected to
      left unilateral torsion (720 degrees rotation in the clockwise direction) without
      including the epididymis. After torsion (2 h) and detorsion (4 h) periods, rats
      were sacrificed and bilateral orchidectomy was performed. Testis tissues were
      washed with cold saline solution, cut into small pieces with scissors, placed
      into glass bottles and homogenised in four volumes of ice-cold Tris-HCl buffer.
      Clear supernatant fluid was used for biochemical analyses. Treating rats with
      CAPE (applied at 10 micro mol/kg, 30 min prior to T/D) attenuated the testicular
      injury, as well as the increase in the tissue levels of myeloperoxidase and
      thiobarbituric acid-reactant substances (TBARS) caused by T/D in the testis.
      Testis tissues showed a significant increase in glutathione peroxidase (GSH-Px)
      activity compared to the torsion group when CAPE was applied. Taken together, our
      results clearly demonstrate that CAPE treatment exerts a protective effect on
      testicular T/D, and part of this effect may be due to inhibiting the neutrophil
      mediated cellular injury.

PMID- 12215860
TI  - Synovial fluid levels of E-selectin and intercellular adhesion molecule-1:
      relationship to joint inflammation in children with chronic arthritis.
AB  - E-selectin and intercellular adhesion molecule (ICAM)-1 are crucial to the
      inflammatory response in chronic inflammatory arthritis. Soluble (s) levels of
      these molecules in sera and synovial fluid (SF) correlate with some clinical
      parameters and synovial tissue expression of the same molecules in rheumatoid
      arthritis. Studies of sera from children with chronic inflammatory arthritis
      corroborate this information; corresponding SF data are relatively lacking. We
      thus studied SF sE-selectin and sICAM-1 in 28 children with active juvenile
      rheumatoid arthritis or a spondyloarthropathy. Levels were correlated with
      erythrocyte sedimentation rate (ESR), SF leukocyte counts, duration of disease,
      and duration of response to concomitant intra-articular corticosteroid injection.
      Levels were compared according to use of methotrexate and/or sulfasalazine.
      Synovial fluid sE-selectin correlated with ESR and SF leukocyte counts. There was
      a trend toward lower sICAM-1 in patients treated with sulfasalazine and/or
      methotrexate. We conclude that SF levels of sE-selectin accurately reflect intra
      synovial inflammation. Soluble ICAM-1 levels may reflect the effects of disease
      modifying agents.

PMID- 12215861
TI  - Objective evidence of abnormal regional cerebral blood flow in patients with
      systemic lupus erythematosus on Tc-99m ECD brain SPECT.
AB  - Technetium-99m ethyl cysteinate dimer (Tc-99m ECD) brain single photon emission
      computed tomography (SPECT) was used to detect abnormal regional cerebral blood
      flow (rCBF) in 78 SLE patients with neuropsychiatric manifestations. These
      patients were separated into two subgroups: group 1 including 48 cases with
      definite neuropsychiatric symptoms/signs and group 2 with 30 cases having no
      neuropsychiatric symptoms/signs. Tc-99m ECD brain SPECT demonstrated
      hypoperfusion brain lesions in 90% and 20% of patients in groups 1 and 2,
      respectively. In both groups, parietal lobe and cerebellum are the most and least
      common areas with hypoperfusion lesions, respectively. This study suggests that
      Tc-99m ECD brain SPECT may provide objective information for detection of
      hypoperfusion brain lesions in SLE patients.

PMID- 12215862
TI  - Activated factor XII in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is associated with premature mortality, with
      approximately 50% of deaths being due to cardiovascular disease. It has been
      shown that the increased incidence of cardiovascular disease is independent of
      traditional risk factors. Previous studies have shown an increased risk of
      coronary heart disease with increased levels of activated factor XII (FXIIa). The
      aim of this study was to investigate levels of FXIIa in patients with RA. We
      studied 32 patients with RA and 30 age- and sex-matched control subjects. We
      found FXIIa levels significantly increased in the patient group, with 56% of the
      patients and 6.7% of controls having levels greater than or equal to 2 ng/ml. A
      previous study has shown that individuals with levels of 2 ng/ml or more have an
      increased risk of coronary heart disease. Measurement of FXIIa could perhaps help
      to identify an 'at risk' group of patients, allowing early intervention therapy.

PMID- 12215863
TI  - Weight bearing following intra-articular steroid injection of the knee: survey of
      current practice and review of the available evidence.
AB  - INTRODUCTION: Intra-articular steroid therapy is one of the most common clinical
      procedures performed by rheumatologists. There is wide variation in the
      postoperative instructions given to patients following such injections. AIM: The
      aim of this study was to determine what advice is given with regards to non
      weight-bearing following steroid injections of the knee by rheumatologists,
      orthopaedic surgeons, and general practitioners (GPs). METHOD: A questionnaire
      examining advice on non-weight-bearing following knee steroid injections was
      posted to 100 rheumatologists, 100 orthopaedic surgeons, and 50 GPs. RESULTS: A
      significant proportion of respondents advised patients to avoid weight bearing
      after injection (42.4%). Most of these advised patients to do so for one (16.3%)
      or two (25.1%) days. As compared to 57.1% of general practitioners and 2.8% of
      orthopaedic surgeons, 70.7% of rheumatologists advised patients to avoid weight
      bearing (P < 0.05). CONCLUSION: A significant proportion of rheumatologists and
      general practitioners performing steroid injections of the knee advise patients
      not to weight-bear postinjection. Examination of the available literature fails
      to reveal strong evidence to support such a practice, which has potentially
      significant implications with regards to loss of working days, costs of mobility
      aids, and patient inconvenience.

PMID- 12215864
TI  - Effects of low power laser and low dose amitriptyline therapy on clinical
      symptoms and quality of life in fibromyalgia: a single-blind, placebo-controlled
      trial.
AB  - The purpose of this study was to examine the effectiveness of low power laser
      (LPL) and low-dose amitriptyline therapy and to investigate effects of these
      therapy modalities on clinical symptoms and quality of life (QOL) in patients
      with fibromyalgia (FM). Seventy-five patients with FM were randomly allocated to
      active gallium-arsenide (Ga-As) laser (25 patients), placebo laser (25 patients),
      and amitriptyline therapy (25 patients). All groups were evaluated for the
      improvement in pain, number of tender points, skin fold tenderness, morning
      stiffness, sleep disturbance, muscular spasm, and fatigue. Depression was
      evaluated by a psychiatrist according to the Hamilton Depression Rate Scale and
      DSM IV criteria. Quality of life of the FM patients was assessed according to the
      Fibromyalgia Impact Questionnaire (FIQ). In the laser group, patients were
      treated for 3 min at each tender point daily for 2 weeks, except weekends, at
      each point with approximately 2 J/cm(2) using a Ga-As laser. The same unit was
      used for the placebo treatment, for which no laser beam was emitted. Patients in
      the amitriptyline group took 10 mg daily at bedtime throughout the 8 weeks.
      Significant improvements were indicated in all clinical parameters in the laser
      group (P = 0.001) and significant improvements were indicated in all clinical
      parameters except fatigue in the amitriptyline group (P = 0.000), whereas
      significant improvements were indicated in pain (P = 0.000), tender point number
      (P = 0.001), muscle spasm (P = 0.000), morning stiffness (P = 0.002), and FIQ
      score (P = 0.042) in the placebo group. A significant difference was observed in
      clinical parameters such as pain intensity (P = 0.000) and fatigue (P = 0.000) in
      favor of the laser group over the other groups, and a significant difference was
      observed in morning stiffness (P = 0.001), FIQ (P = 0.003), and depression score
      (P = 0.000) after therapy. A significant difference was observed in morning
      stiffness (P = 0.001), FIQ (P = 0.003), and depression (P = 0.000) in the
      amitriptyline group compared to the placebo group after therapy. Additionally, a
      significant difference was observed in depression score (P = 0.000) in the
      amitriptyline group in comparison to the laser group after therapy. Our study
      suggests that both amitriptyline and laser therapies are effective on clinical
      symptoms and QOL in fibromyalgia and that Ga-As laser therapy is a safe and
      effective treatment in cases with FM. Additionally, the present study suggests
      that the Ga-As laser therapy can be used as a monotherapy or as a supplementary
      treatment to other therapeutic procedures in FM.

PMID- 12215866
TI  - Transdermal fentanyl for the treatment of back pain caused by vertebral
      osteoporosis.
AB  - Pain relief for patients with osteoporosis is important to maintain mobility and
      facilitate physical therapy. Transdermal fentanyl may be useful but has not been
      studied systematically. Patients with at least one osteoporotic vertebral
      fracture requiring strong opioids were enrolled and received transdermal
      fentanyl. Treatment history, pain, ease of physical therapy, and quality of life
      were recorded at baseline and after 4 weeks. Of 64 patients enrolled, 49
      completed the study; 12 withdrew because of adverse events, most commonly nausea,
      vomiting, or dizziness. Pain at rest and on movement decreased significantly from
      baseline to final assessment (mean scores 7.84 and 8.55, respectively, at
      baseline, falling to 3.56 and 4.50 after 4 weeks). Quality of life improved
      significantly, and 61% of patients were satisfied with the treatment. Ability to
      undergo physical therapy improved significantly. Transdermal fentanyl is useful
      for the treatment of severe back pain caused by osteoporosis.

PMID- 12215865
TI  - Possible pathogenetic role of new cytokines in postmenopausal osteoporosis and
      changes during calcitonin plus calcium therapy.
AB  - The present study was designed to test if the serum cytokines (interleukin, or IL
      1beta, -2, -2r, -6, -6r, -8, and -10, and tumor necrosis factor alpha, or TNF
      alpha) and osteocalcin levels were different between 50 osteoporotic and 30
      postmenopausal nonosteoporotic women and to evaluate the efficacy of calcitonin
      therapy during 6 months on serum cytokines and osteocalcin levels in
      postmenopausal osteoporotic women. In our study, serum levels of osteocalcin, TNF
      alpha, IL-2, and IL-8 were significantly higher in the patient group (P < 0.05),
      whereas serum levels of IL-10 and IL-6r were significantly lower in the patient
      group (P < 0.05). When analysed separately according to bone turnover, serum
      levels of IL-10 and IL-6r were significantly lower in the normal-turnover group
      (P < 0.05), and IL-2, IL-8, and TNF-alpha were significantly higher in the high
      turnover group than in the control group (P < 0.05). Statistically significant
      improvement seemed to happen in the patients receiving calcitonin plus calcium
      therapy (P < 0.05) concerning levels of serum IL-6r at the 1st month (P < 0.05),
      IL-10, IL-2r, IL-6r, and osteocalcin at the 3rd month, and IL-6r and osteocalcin
      at the end of the 6th month. Our findings demonstrate that calcitonin plus
      calcium therapy appears to be particularly more effective for patients with high
      turnover. In addition, our study suggests that IL-10 and IL-6r may have an
      important role in normal-turnover osteoporosis, while IL-2, IL-8, and TNF-alpha
      may play an important role in high-turnover postmenopausal osteoporosis.

PMID- 12215867
TI  - Effect of methotrexate on pulmonary function in patients with rheumatoid
      arthritis--a prospective study.
AB  - If given in high doses, methotrexate (MTX), a folate antagonist, could cause
      pulmonary complications. To evaluate the pulmonary effects of low-dose
      methotrexate, 55 newly diagnosed patients with rheumatoid arthritis (RA)
      prescribed with MTX were studied prospectively. A significant reduction in
      percent predicted values of forced expiratory volume (FEV(1)), forced vital
      capacity (FVC), total lung capacity (TLC), and functional residual capacity (FRC)
      was observed after 2 years of MTX treatment. A significant increase in the
      FEV(1):FVC ratio was also observed. In comparison to the normal annual decline in
      healthy adults, the actual reduction in observed values in the patients was
      significantly greater (3.2, 6.3, and 6.7 times normal for FEV(1), FVC, and TLC,
      respectively). PaO(2) and oxygen saturation showed marginal but significant
      improvement. It was concluded that low-dose MTX treatment in RA might cause an
      accelerated decline in lung function. Therefore, periodic monitoring of pulmonary
      function among RA patients started on MTX could be necessary.

PMID- 12215868
TI  - Prevalence of radiographic osteoarthritis of the hands in Saudi Arabia.
AB  - We studied the radiographic evidence of osteoarthritis (OA) of the hands in 300
      patients (167 male, 133 female) attending 14 primary care facilities for a
      variety of medical conditions. Radiographic OA was seen in 30.3% of males and
      36.3% of females. Most commonly affected were the metacarpophalangeal joints,
      followed by the distal interphalangeal and carpometacarpophalangeal joints.

PMID- 12215870
TI  - Recurrent bronchiolitis obliterans organizing pneumonia in a patient with limited
      cutaneous systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a generalized disorder characterized by fibrosis and
      vascular obliteration in the skin, lung, gastrointestinal tract, and kidney. One
      of its two subsets is a stable, limited cutaneous group (lSSc). Pulmonary
      involvement in scleroderma is common, and several types of pulmonary disorders
      are associated with SSc. Bronchiolitis obliterans organizing pneumonia (BOOP) is
      a rare finding in lung disorders associated with SSc. We describe a case of lSSc
      with BOOP that was responsive to steroid therapy. Of interest is that the lung
      disorders appeared in different periods and areas. It might be important to
      diagnose abnormal shadows in lung fields before treatment of patients with SSc.

PMID- 12215869
TI  - Pulmonary alveolar microlithiasis after Varicella zoster infection in a patient
      presenting with antiphospholipid syndrome and discoid lupus.
AB  - We present a case with diagnosis of pulmonary alveolar microlithiasis that
      illustrates the appearance of this rare chronic lung disease on conventional
      chest X-ray, high-resolution CT, and transbronchial lung biopsy. This is the
      first case reported which developed pulmonary alveolar microlithiasis after
      Varicella zoster infection in a patient with antiphospholipid antibodies and
      discoid lupus.

PMID- 12215871
TI  - [Tourette's syndrome - a review].
AB  - Tourette's syndrome (TS) is a neuropsychiatric disorder characterised by the
      occurrence of chronic motor and vocal tics that usually begin in childhood. A
      prevalence of 4-5/10.000 individuals is estimated. Tourette's syndrome patients
      frequently show comorbidity with other psychiatric disorders such as obsessive
      compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD),
      anxiety, and affective disorders. Some forms of OCD seem to share a common
      genetic etiology with TS and to be a facultative part of the TS phenotypic
      spectrum. Based on MRI, positron emission tomography (PET), and single photon
      emission computed tomography (SPECT), data alterations in the cortico-striato
      pallido-thalamo-cortical functional systems have been discussed. Within these
      systems, dopaminergic neurotransmission is thought to play an important role in
      the pathophysiology of TS. Autoimmunological mechanisms seem to be important in
      some subtypes of TS and OCD that are triggered or exacerbated by infections with
      hemolytic streptococci. In these cases, immune modulatory therapy proved to be
      efficient. To date, there is no established treatment regimen for TS. The
      medications used most frequently are antipsychotics.

PMID- 12215872
TI  - [Is the borderline personality disorder a complex post-traumatic stress disorder?
      - The state of research].
AB  - Regarding the high prevalence of traumatic experiences in patients with
      borderline personality disorders (BPD), we review the available literature
      focussing on the hypothesis that BPD is a subtype of trauma associated disorders.
      The criteria of BPD, of complex post-traumatic stress disorders (PTSD), and of
      disorders of extreme stress not otherwise specified (DESNOS) substantially
      overlap. Research of the long-term course of BPD and PTSD, trauma research, and
      research of vulnerability in both disorders yielded converging results.
      Neuropsychological deficits in BPD and PTSD as well as psychoendocrinological and
      neuroimaging studies in BPD und PTSD also revealed common features. A
      pathogenetic specificity of individual etiologic factors does not appear to
      exist, however the assumption of a diathesis-stress model with traumatisation as
      a necessary but etiologically insufficient condition seems justified. Further
      research will have to prove BPD as a complex and early-onset post-traumatic
      stress disorder after multiple and/or chronic (type II) traumatic experiences
      during childhood and/or youth. Definitive conclusions require further research
      efforts.

PMID- 12215873
TI  - [Wender Utah rating scale. The short-version for the assessment of the attention
      deficit hyperactivity disorder in adults].
AB  - This work presents a statistical analysis of the German version of the Wender
      Utah rating scale (WURS) for the retrospective diagnosis of attention
      deficit/hyperactivity disorder (ADHD) in adults. Data were obtained from 703
      subjects. Item selection according to item-total correlation scores, frequency,
      and plausibility led to a short version of the scale that includes 21 items with
      item-total correlations from 0.19 to 0.61. Retest reliability of the WURS-k was
      r=0.9.

PMID- 12215874
TI  - [Micro-Mental Test - a short method of dementia screening].
AB  - Especially in outpatient settings, dementia is still an underdiagnosed syndrome.
      The Micro-Mental Test has been developed as a short version of the Mini-Mental
      Status Examination (MMSE). We examined the reliability and diagnostic validity of
      a German version (Mikro-Mental Test). We administered the MMSE and the German
      version of the Micro-Mental Test to 20 inpatients of a geriatric psychiatry
      hospital (mean age 74.8+/-8.1 years), 55 patients from a cognitive clinic (mean
      age 71.9+/-9.1 years), and 27 healthy older adults (mean age 68.5+/-4.1 years).
      Diagnoses made by an experienced psychiatrist according to ICD-10 criteria served
      as external criteria. The mean duration for testing with the Micro-Mental Test
      was 8 min, and with the MMSE 15 min. Test-retest analyses showed satisfactory
      reliability. With regard to sensitivity and specificity, we found comparable
      diagnostic validity for the MMSE and the Micro-Mental Test. We suggest that, due
      to its brevity and diagnostic validity, the Micro-Mental Test is a useful tool
      for dementia screening in an outpatient setting.

PMID- 12215875
TI  - [Structural cerebral changes in subjects with mild cognitive impairment].
AB  - The aim of the present study was to investigate the morphological changes in
      subjects with mild cognitive impairment (MCI) revealed by quantitative magnetic
      resonance imaging (MRI). Twenty-one subjects with cognitive impairment and 22
      healthy controls were compared with 12 patients suffering from mild Alzheimer's
      disease (AD). The volumes of the following brain structures were assessed: total
      intracranial compartment, cerebrospinal fluid compartment, whole brain, and
      medial temporal substructures (hippocampus and parahippocampal gyrus). Subjects
      with mild cognitive impairment showed a significantly reduced volume of the right
      parahippocampal gyrus over healthy controls. Volumes of the other regions and
      structures did not differ between the MCI group and controls. The volumetric and
      neuropsychological findings of the present study support the hypothesis that mild
      cognitive impairment - at least in some of the affected individuals - can be seen
      as a preclinical stage of AD and that atrophy of the parahippocampal gyrus might
      be useful as an early marker of AD.

PMID- 12215876
TI  - [Depression among the elderly in Switzerland].
AB  - Data for this analysis came from a cross-sectional study on dementia, depression,
      and disability conducted in Zurich and Geneva in 1995/96. The random sample
      stratified by age and gender consisted of 921 subjects aged 65 and more. Based on
      the Canberra Interview for the Elderly, depression was assessed by means of
      psychogeriatric assessment scales (PAS) according to DSM-III-R criteria. The
      number of depressive symptoms (NDS) and the prevalence rate of depression (PRD)
      were computed for the whole sample as well as according to age and gender. To
      evaluate the independent effects of age as well as gender with regard to the risk
      of being depressed, multivariate analyses were conducted. On average, 13% of
      females vs 8% of males reported having at least one depressive symptom. The PAS
      yielded 298 (41.8%) subjects without depressive symptoms, 341 (50.2%) with 1-3
      symptoms, and 60 (8.0%) with four or more. The average NDS was 1.27 (95% CI 1.16
      1.39). For females, NDS values statistically significantly higher than those for
      males were calculated (1.53, 95% CI 1.35-1.70 vs 1.05, 95% CI 0.90-1.20). The NDS
      increased significantly with age. Subjects with low education levels and being
      divorced or widowed had statistically significantly higher NDS values than highly
      educated, married, or single persons. There were strong positive associations
      between NDS, dementia, and activities of daily living. Multivariate regression
      analysis revealed gender - however, not age - as a strong risk factor for NDS.
      Overall PRD amounted to 8.0% (95% CI 5.7-10.2%). Females had statistically
      significantly higher PRD values than males (10.4%, 95% CI 7.0-13.9% vs 3.9, 95%
      CI 2.0-5.9%). The PRD increased substantially with age. After adjustment for
      other risk factors, multivariate logistic regression analysis confirmed the
      positive statistically significant association between age, gender, and
      depression.

PMID- 12215877
TI  - [Addiction in the elderly - an underestimated diagnosis in clinical practice?].
AB  - According to several studies in the USA, alcohol abuse is common among elder
      people, particularly among those admitted to hospital. Corresponding data for
      Germany are lacking as yet. In this study, the frequency of addiction problems in
      the elderly admitted to hospital was investigated using the data from 1990 to
      1998 of the psychiatric department at the General University Hospital of Lubeck,
      Germany. Furthermore, the documentations of all consultations in that period were
      reevaluated. The psychiatric consultation service covers two general hospitals
      providing inpatient treatment for about 200,000 inhabitants. Diagnoses were made
      according to the ICD-10 criteria. In 17.7% of the males older than 64 years and
      in 4.2% of the elderly females admitted to the psychiatric department, alcohol
      dependency was diagnosed, while 5.8% of the elderly patients showed substance
      abuse, most often of benzodiazepine. Among the patients visited in the
      psychiatric consultation service, 10.8% of the elderly males and 3.2% of the
      elderly females were alcohol addicts and 3.9% substance abusers. The frequency of
      alcohol-induced neuropsychiatric complications, particularly withdrawal delirium
      and amnestic syndrome, increased with age. Also, benzodiazepine withdrawal
      delirium most frequently occurred in older patients. These results underscore
      that, although the prevalence rate seems to be lower than among the younger
      population, in the elderly population substance abuse still is a relevant medical
      problem, since the rate of neuropsychiatric complications increased with age.

PMID- 12215878
TI  - [Disguised Tourette's syndrome. A contribution to the differential diagnosis on
      phobia and fear].
AB  - Patients with Tourette's syndrome often develop multiple psychopathological
      symptoms beyond the basic symptoms (motor and vocal tics). We describe a female
      patient who had been treated over years with cognitive-behavioural methods under
      the diagnosis of anxiety disorder without success. Her obsessive-compulsive and
      tic symptoms had been ignored because they had not been reported by the patient,
      who was accustomed to them. Our case underlines the necessity of specific
      exploration and taking of a case history, especially when symptoms are atypical
      and do not improve under treatment. This gives cause for some critical remarks on
      the principle of comorbidity.

PMID- 12215879
TI  - [Late onset Huntington's disease - a differential diagnosis of Alzheimer's
      disease].
AB  - A 66-year-old patient was admitted to our memory clinic for diagnostic evaluation
      of potential Alzheimer's disease (AD). Her family reported progressive
      disturbances of memory, irritability, fidgetiness, and abrupt movements of the
      extremities and the head for the last 3 to 4 years. Family history was positive
      for progressive cognitive deterioration associated with movement disturbances
      beginning at the age of 65 years. Examination revealed mild dementia as well as
      involuntary choreatiform movements of the extremities and the head. Genetic
      testing showed an expanded CAG repeat of 41 in the Huntington's disease (HD) gene
      leading to the diagnosis of HD with mild dementia. Because the age of onset of HD
      is typically between 35 to 50 years, HD is rarely considered as a differential
      diagnosis for dementia in elderly patients. This case shows the relevance of an
      accurate differential diagnosis of cognitive disturbances in order to detect rare
      causes of dementia.

PMID- 12215880
TI  - [Alzheimer's dementia or cerebral toxoplasmosis? Case study of dementia following
      toxoplasmosis infection].
AB  - Cerebral toxoplasmosis can lead to dementia in AIDS and in immunodeficient
      patients. We present a case study in which cerebral toxoplasmosis was associated
      with a dementia of Alzheimer type. Half a year to one year before the cognitive
      impairment began, the patient suffered a subacute infection of toxoplasmosis at
      the age of 56. Neuropsychological examination as well as MRI suggested a
      diagnosis of dementia with infectious genesis. However, serological tests showed
      only little evidence of infection. Since the results of the PET examination
      indicated changes in the glucose metabolism typical of Alzheimer's disease, we
      infer a comorbidity of cerebral toxoplasmosis and dementia of Alzheimer type.

PMID- 12215881
TI  - [Presenile dementia in polycystic lipomembranous osteodysplasia].
AB  - We present a 36-year-old woman with a 3-year history of cognitive decline
      followed by development of a small stepped gait and urinary and fecal
      incontinence. Workup revealed multiple bone cysts documented by X-ray and
      idiopathic hyperprolactinoma. An MRI confirmed the CT finding of massive
      bilateral basal ganglia calcification. This is the first case of polycystic
      lipomembranous osteodysplasia described in Germany. We conclude that patients
      with presenile dementia, psychosis, or early-onset Parkinsonism associated with
      basal ganglia calcification should undergo X-rays of hand and feet to rule out
      polycystic lipomembranous osteodysplasia.

PMID- 12215882
TI  - [Correlation of diffusion-weighted magnetic resonance imaging with neurological
      deficits in sporadic Creutzfeldt-Jakob Disease].
AB  - This case report describes the sporadic Creutzfeldt-Jakob disease (CJD) of a 53
      year-old man who initially complained about vertigo and dizziness. Within 18
      weeks, he developed impaired memory, hemineglect, and sensory impairment of the
      left half of the body. A CSF tap was positive for 14-3-3 protein and showed
      increased tau protein, neuron-specific enolase (NSE), and the astroglial protein
      S-100 B. The EEG showed right temporal sharp waves without periodicity. Diffusion
      weighted MRI revealed hyperintensities in the right temporo-occipital cortex
      which corresponded well with hypometabolic areas in a PET scan and the
      neurological and neuropsychological deficits. The morphological FLAIR T2 MRI
      showed no pathological changes. Within 20 weeks, the patient developed severe
      dementia with decreased spatial orientation and myoclonia, became incontinent,
      and was confined to bed. He died within 22 weeks after the first presentation of
      symptoms.

PMID- 12215883
TI  - [Levodopa dependency in Parkinson's disease: case report and review].
AB  - Only a few patients with Parkinson's disease and levodopa dependency or abuse
      have been reported. We present a 35-year-old patient with young-onset Parkinson's
      disease who developed motor complications, levodopa dependency, and drug-induced
      psychosis after primary treatment with levodopa. Diagnostic criteria and
      treatment guidelines for this neuropsychiatric disorder are presented as well as
      a tentative neurobiological answer to the question of why levodopa dependency is
      observed only in a minority of patients with Parkinson's disease.

PMID- 12215884
TI  - [Hawaiian baby woodrose: (Psycho-) Pharmacological effects of the seeds of
      Argyreia nervosa. A case-orientated demonstration].
AB  - The seeds of the Hawaiian baby woodrose ( Argyreia nervosa) are used by
      adolescents as a supposed hallucinogenic drug. These seeds are legally available
      and broadly sold. The active components are alkaloids structurally related to
      lysergic acid diethylamide (LSD). However, the psychic effects are very different
      from those of LSD and are dominated by rather sedative, uncomfortable autonomic
      disturbances similar to the effects of scopolamine. The (psycho)pharmacological
      profile is described on the basis of the active substances lysergacidamide and
      lysergacidethylamide (and their isomers). It is shown that neither the substances
      themselves nor the mixture are able to evoke LSD-like perceptual variances. The
      exposure of Argyreia nervosa is described focusing on potential fetal distress by
      contained ergometrine and the case history of an intoxication.

PMID- 12215885
TI  - [Leptin and psychiatric disorders].
AB  - As early as the beginning of the 20th century, changes in appetite and weight
      were recognized as important symptoms of severe psychiatric disorders.
      Particularly in the last decade, understanding of the regulation of appetite and
      weight has made major progress. In this context, the discovery of the adipose
      tissue hormone leptin, which signals the size of the peripheral fat stores to the
      CNS, was crucial. In addition, leptin is also involved in a number of CNS
      networks regulating behavior and thus of great importance for the pathophysiology
      of psychiatric disorders. Apart from sexual behavior, those networks include
      motor activity, sleep, and cognition. Moreover, leptin seems to be involved in
      the development and maturation of the brain. The present paper summarizes current
      studies which suggest that, in psychiatric disorders, leptin could be of
      importance not only for disease-associated or drug-related changes in appetite
      and weight but also for alterations in behavior and cognition.

PMID- 12215887
TI  - A gene therapy for cancer based on the angiogenesis inhibitor, vasostatin.
AB  - The growth and persistence of solid tumors and their metastasis are angiogenesis
      dependent. Vasostatin, the N-terminal domain of calreticulin inclusive of amino
      acids 1-180, is a potent angiogenesis inhibitor. To investigate whether
      intramuscular administration of vasostatin gene has the antitumor activity in
      mouse tumor models, we constructed a plasmid DNA encoding vasostatin and a
      control vector. Production and secretion of vasostatin protein by COS cells
      transfected with the plasmid DNA encoding vasostatin (pSecTag2B-vaso) were
      confirmed by Western blot analysis and ELISA. Conditioned medium from vasostatin
      transfected COS cells apparently inhibited human umbilical vein endothelial cell
      (HUVEC) and mouse endothelial cell (SVEC4-10) proliferation, compared with
      conditioned medium from the COS cells transfected with control vector or non
      transfected cells. Treatment with pSecTag2B-vaso twice weekly for 4 weeks
      resulted in the inhibition of tumor growth and the prolongation of the survival
      of tumor-bearing mice. The sustained high level of vasostatin protein in serum
      could be identified in ELISA. Angiogenesis was apparently inhibited in tumor by
      immunohistochemical analysis. Angiogenesis was also inhibited in the chicken
      embryo CAM assay and mouse corneal micropocket assay. The increased apoptotic
      cells were found within the tumor tissues from the mice treated with plasmid DNA
      encoding vasostatin. Taken together, the data in the present study indicate that
      the cancer gene therapy by the intramuscular delivery of plasmid DNA encoding
      vasostatin, is effective in the inhibition of the systemic angiogenesis and tumor
      growth in murine models. The present findings also provide further evidence of
      the anti-tumor effects of the vasostatin, and may be of importance for the
      further exploration of the application of this molecule in the treatment of
      cancer.

PMID- 12215888
TI  - Gene transfer of soluble TGF-beta type II receptor inhibits experimental
      proliferative vitreoretinopathy.
AB  - This study was conducted to investigate a method of gene therapy for
      proliferative vitreoretinopathy (PVR) by inhibiting type beta transforming growth
      factor (TGF-beta). PVR was induced in pigmented rabbits by intravitreal injection
      of 50 000 rabbit conjunctival fibroblasts after vitrectomy. Subsequently, the
      eyes received an intravitreal application of adenovirus vector encoding a soluble
      type II TGF-beta receptor (AdTbeta-ExR, n = 10) or adenoviral vector expressing
      beta-galactosidase (AdLacZ) (n = 10) or balanced salt solution (BSS) (n = 6). The
      eyes were examined ophthalmoscopically for 28 days after surgery, and the
      clinical stage of PVR was evaluated on a scale of zero to five. Histological
      examinations were performed on the treated eyes on day 28. All control eyes
      injected with AdLacZ or BSS developed PVR, characterized by retinal detachment
      and the formation of intravitreal membranes within 7 days. The eyes injected with
      AdTbeta-ExR also developed features of PVR, but the average severity from day 5
      to day 28 was significant lower than in the control eyes (P < 0.05). TGF-beta
      plays an important role in PVR progression in a PVR model, and prevention of TGF
      beta signaling could be therapeutically useful.

PMID- 12215886
TI  - Replication competent helper functions for recombinant AAV vector generation.
AB  - Adeno-associated virus (AAV) is a promising gene transfer vector tested in both
      animal studies and human clinical trials. However, current production methods are
      generally inefficient and require improvements to meet the increasing clinical
      need for economical, high titer and high quality rAAV vectors. The inefficiency
      of the current systems largely arises from the AAV helper function, which
      contains only the AAV coding region but lacks inverted terminal repeats. The
      terminal repeats were originally removed to prevent replication competent AAV
      contamination. Here we designed a novel and highly efficient rAAV helper function
      containing AAV terminal repeats. The new helper function not only mimics the wild
      type AAV growth as it replicates along with the vector plasmid, but also restores
      the cis regulating function of the AAV terminal repeats. Addition of heterologous
      introns to the helper genome and use of a mutant AAV terminal repeat defective in
      packaging effectively controls the contamination of replication competent AAV
      particles. This new strategy also performs better in AAV producing cell lines
      than those based on non-replicating AAV rep and cap genome.

PMID- 12215889
TI  - Prevention and regression of atopic dermatitis by ointment containing NF-kB decoy
      oligodeoxynucleotides in NC/Nga atopic mouse model.
AB  - Atopic dermatitis, a chronic inflammatory skin disease characterized by relapsing
      eczema and intense prurigo, requires effective and safe pharmacological therapy.
      In this study, we examined the efficacy of ointment containing NF-kB decoy
      oligodeoxynucleotides (ODN) on atopic dermatitis lesions in NC/Nga mice, which
      are characterized by the spontaneous onset of atopic dermatitis in conventional
      conditions. Topical administration of NF-kB decoy ODN twice a month resulted in a
      significant reduction in clinical skin condition score and marked improvement of
      histological findings. Reduction of the atopic skin condition by NF-kB decoy ODN
      was accompanied by a significant decrease in migration of mast cells into the
      dermis and an increase in apoptotic cells. Here, we demonstrated the successful
      treatment of atopic dermatitis with ointment containing NF-kB decoy ODN in a
      mouse model, promising new therapy for atopic dermatitis.

PMID- 12215890
TI  - Robust and prolonged gene expression from injectable polymeric implants.
AB  - We introduce an injectable system for the formation of a biodegradable DNA
      containing implant that releases DNA over a 2-month period to provide a robust
      and prolonged gene expression at the site. Sustained delivery of the appropriate
      plasmid DNA resulted in sustained expression of luciferase, the persistent
      appearance of secreted alkaline phosphatase in the serum and small blood vessel
      formation in the vicinity of the implant from the delivery of the development
      endothelial locus-1 gene. Local expression of development endothelial locus-1
      protein promotes the development of blood vessels to meet the metabolic demands
      of new tissue and is a paradigm for the delivery of other growth factors that act
      locally to aid tissue regeneration. This delivery system involves simple
      preparation procedures and can be injected directly into the site, hence should
      be a useful approach to plasmid-based gene transfer for vaccination and tissue
      engineering.

PMID- 12215891
TI  - Adenovirus-based libraries: efficient generation of recombinant adenoviruses by
      positive selection with the adenovirus protease.
AB  - Adenoviruses (Ad) deleted in the protease (PS) gene are capable of only one round
      of replication in non-complementing cells. This feature was exploited to develop
      a positive selection method for constructing adenoviral recombinants using
      ectopic expression of the PS gene in the E1 region. Very low levels of PS were
      sufficient to ensure the rescue of a PS-deleted Ad genome (Ad(Delta)PS), thereby
      eliminating deleterious effects PS over-expression might exert on cell or virus
      growth. In addition to the standard co-transfection method, an alternative
      protocol was developed in which the Ad5-(Delta)PS viral DNA was delivered by
      infection before subsequent transfection of 293 cells with the transfer vector.
      Under optimal conditions, at least one recombinant Ad per 10(3) cells was
      generated with 100% of the plaques being recombinant. Since the
      infection/transfection protocol is readily scalable, this represents the first
      method that allows for the easy construction of adenovirus vector (AdV) libraries
      with high diversities. This approach addresses in a novel way the bottleneck
      encountered when converting plasmid libraries, constructed in E. coli using a
      variety of well-established strategies, into corresponding AdV libraries. It
      maintains high diversity while generating recombinant viruses with 100%
      efficiency.

PMID- 12215892
TI  - Electroporation-mediated pain-killer gene therapy for mononeuropathic rats.
AB  - The relatively low expression levels achieved from transferred genes have limited
      the application of nonviral vectors for gene transfer into the spinal cord in
      vivo. Thus, the aim of this study was to evaluate the efficacy of electroporation
      mediated pro-opiomelanocortin (POMC) gene therapy for neuropathic pain using an
      animal model of chronic constrictive injury (CCI). Firstly, the optimal pulse
      characteristics (voltage, pulse duration, number of shocks) were investigated for
      in vivo electroporation-mediated gene transfer into the spinal cord. The
      electroporation process makes use of plasmid DNA, which expresses the POMC gene.
      Expression levels were evaluated in this study by Western blot. We conclude that
      the optimal conditions for electroporation are a pulse voltage of 200 V, 75-ms
      duration, 925-ms interval, for five iterations. Secondly, electroporation
      treatment for neuropathic pain was attempted on CCI rats using plasmid DNA that
      expresses the POMC gene. Intrathecal administrations of the POMC vector elevated
      spinal beta-endorphin levels, as manifested in a significantly elevated pain
      threshold for the CCI limbs. This result suggests that gene therapy for
      neuropathic pain using this novel technique is very efficacious, and thus shows
      promise for further clinical trials.

PMID- 12215893
TI  - Enhanced gene expression in mouse muscle by sustained release of plasmid DNA
      using PPE-EA as a carrier.
AB  - Delivery of plasmid DNA by nanoparticles improves the DNA bioavailability, for
      instance in intramuscular administration, by localizing the DNA in the muscle
      tissue. Extracellular sustained release of the DNA may lead to more prolonged
      transgene expression. The present study describes a novel controlled gene
      delivery system based on a water soluble and biodegradable polyphosphoester,
      poly(2-aminoethyl propylene phosphate) (PPE-EA). The polymer degraded in PBS at
      37 degrees C through the cleavage of the backbone phosphate bonds, and it was
      synthesized with a relative high molecular weight to ensure a suitable hydrolytic
      stability as a gene carrier. The tissue response and cytotoxicity study
      demonstrated a better tissue compatibility of PPE-EA in mouse muscle compared
      with commonly used polyethylenimine and poly-L-lysine. PPE-EA condensed DNA
      efficiently and protected DNA from nuclease and serum degradation. Sustained
      release of plasmid was achieved from PPE-EA/DNA complexes as a result of PPE-EA
      degradation. The DNA release profiles appear to be predominantly controlled by
      carrier degradation and the release rate of plasmid could be adjusted by varying
      the charge ratio of PPE-EA to DNA. At an N/P (amino to phosphate groups) ratio of
      1, a 46% burst was observed for the first day, followed by about 4% release per
      day (24 microg DNA/day/mg of complex) for 12 days. Higher charge ratios reduced
      both the DNA release rate and the burst effect. The released DNA retained its
      structural and functional integrity. Intramuscular injection of PPE-EA-p43-LacZ
      complexes at N/P ratios of 0.5 and 1 resulted in enhanced beta-galactosidase
      expression in anterior tibialis muscle in Balb/c mice, as compared with naked DNA
      injections. Similarly, PPE-EA/IFN(alpha)2b DNA complexes generated an increased
      systemic level of interferon-alpha2b in mouse serum following intramuscular
      injection, as compared with naked DNA injection.

PMID- 12215894
TI  - Mechanisms involved in development of resistance to adenovirus-mediated
      proapoptotic gene therapy in DLD1 human colon cancer cell line.
AB  - To evaluate resistance that develops in cancer cells during treatment with
      adenoviral vectors expressing proapoptotic genes, we repeatedly treated the human
      colon cancer cell line DLD1 with adenoviral vectors expressing the human Bax gene
      and the human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      gene. DLD1 cells resistant to the Bax- or TRAIL-expressing adenoviral vectors
      were then selected and designated as DLD1/Bax-R or DLD1/TRAIL-R cells,
      respectively. Further study showed that resistance in DLD1/Bax-R cells was caused
      by resistance to adenoviral infection, which can be overcome by dose escalation
      of the adenoviral vectors. However, resistance in DLD1/TRAIL-R cells was caused
      by resistance to the TRAIL gene. Therefore, different mechanisms are involved in
      the development of resistance during adenovirus-mediated proapoptotic gene
      therapy. A survey of molecules involved in TRAIL- or Bax-mediated apoptotic
      pathways showed no significant change in expression of death receptors, death
      decoy receptors; FLIP; Bcl-2; Bcl-xS; Bax; Bak; XIAP or caspase-2, -7, -8, or -9
      in either DLD1/Bax-R or DLD1/TRAIL-R cells. Bcl-xL expression detected in both
      mRNA and protein level assays was three times higher in DLD1/TRAIL-R cells than
      in parental or DLD1/Bax-R cells. However, transfection of DLD1 cells with the Bcl
      xL gene showed that overexpression of Bcl-xL is not sufficient for the
      resistance. Moreover, DLD1/Bax-R cells were sensitive to adenoviral vectors that
      expressed the TRAIL gene, but resistant to adenoviral vectors that expressed the
      Bak gene. In contrast, DLD1/TRAIL-R cells were sensitive to adenoviral vectors
      that expressed either Bax or Bak gene. Thus, alternative application of
      adenoviral vectors that expressed proapoptotic genes in different pathways or
      different cell killing models may delay or prevent development of resistance in
      adenovirus-mediated proapoptotic gene therapy.

PMID- 12215895
TI  - The genetic etiology of systemic lupus erythematosus: a short dispatch from the
      combat zone.

PMID- 12215896
TI  - A genome screen of systemic lupus erythematosus using affected-relative-pair
      linkage analysis with covariates demonstrates genetic heterogeneity.
AB  - Systemic lupus erythematosus (SLE) appears to be the consequence of complex
      genetics and of only partly understood environmental contributions. Previous work
      by ourselves and by others has established genetic effects on 1q, 2q, 4p, 6p, and
      16p using SLE as the phenotype. However, individual SLE affecteds are
      extraordinarily different from one another by clinical and laboratory measures.
      This variation may have a genetic basis; if so, it is advantageous to incorporate
      measures of between-family clinical variability as covariates in a genetic
      linkage analysis of affected relative pairs (ARPs) to allow for locus
      heterogeneity. This approach was applied to genome scan marker data from 160
      pedigrees multiplex for SLE and containing 202 ARPs. Because the number of
      potential covariates was large, we used both ad hoc methods and formal principal
      components analysis to construct four composite covariates using the SLE
      classification criteria plus age of onset, ethnicity, and sex. Linkage analysis
      without covariates has detected evidence for linkage at 1q22-24, 2q37, 4p16,
      12p12-11, and 17p13. Linkage analysis with these covariates uncovered linkage at
      13p11, 17q11-25, and 20q12 and greatly improved evidence for linkage at 1q22-24,
      2q37, 12p12-11, and 17p13. Follow-up analysis identified the original variables
      contributing to locus heterogeneity in each of these locations. In conclusion,
      allowing for locus heterogeneity through the incorporation of covariates in
      linkage analysis is a useful way to dissect the genetic contributions to SLE and
      uncover new genetic effects.

PMID- 12215897
TI  - Dominant NZB contributions to lupus in the (SWR x NZB)F1 model.
AB  - (SWR x NZB)F1 (or SNF1) mice succumb to lupus nephritis. Analysis of NZB x SNF1
      backcross mice has recently revealed the existence of four dominant SWR loci (H2
      on Chr 17, Swrl-1 on Chr 1, Swrl-2 on Chr 14 and Swrl-3 on Chr 18), and two NZB
      loci (Nba1 and Lbw2/Sbw2, both on Chr 4) conferring lupus susceptibility. The
      present study focusing on a panel of 88 SWR x SNF1 backcross mice reveals the
      existence of five suggestive loci for antinuclear antibody formation, consisting
      of three dominant NZB contributions (Nba4 on Chr 5, Lbw4 on Chr 6, and Nba5 on
      Chr 7), and two recessive SWR contributions (Swrl-1 on Chr 1, and Swrl-4 on Chr
      10). In addition, this study reveals a dominant NZB locus for GN (Nba3 on Chr 7,
      peak at 31 cM), and a dominant NZB locus linked to early mortality, on Chr 10
      (peak at 4 cM). Collectively, these studies suggest that lupus in the SNF1 strain
      is the epistatic end-product of four dominant SWR loci and four dominant NZB
      loci. The immunological functions and molecular identities of these loci await
      elucidation.

PMID- 12215898
TI  - Polymorphisms of human CD19 gene: possible association with susceptibility to
      systemic lupus erythematosus in Japanese.
AB  - CD19 regulates the signaling for B lymphocyte development, activation and
      proliferation. In mice, CD19 deficiency and overexpression were shown to result
      in hypogammaglobulinemia and autoantibody production, respectively. In the
      present study, we screened for the polymorphisms of CD19, and examined the
      detected polymorphisms for the association with rheumatoid arthritis (RA),
      Crohn's disease and systemic lupus erythematosus (SLE). Two SNPs, c.705G>T (P235P
      and IVS14-30C>T, were decreased (P = 0.0096 and P = 0.028, respectively), in SLE.
      A GT repeat polymorphism, c.*132(GT)(12-18), was detected within the 3'
      untranslated region, and individuals with > or =15 times repeat was significantly
      increased in the independent two groups of Japanese SLE patients (P = 0.011 and P
      = 0.035, respectively); the overall difference between total SLE and controls was
      striking (P = 0.0061). No association was observed for RA and Crohn's disease. In
      addition, no variations other than the common polymorphisms were detected in four
      patients with common variable immunodeficiency, the phenotype of which resembles
      CD19 deficient mice. In Caucasian SLE families, this GT repeat polymorphism was
      rare. CD19 mRNA level in the isolated peripheral blood B lymphocytes was lower in
      individuals possessing (GT)(15-18) alleles compared with those without these
      alleles, both in controls and in SLE patients; however, the difference did not
      reach statistical significance. These results suggested that either the slight
      reduction in the CD19 mRNA level associated with the elongation of GT repeat, or
      an allele of another locus in linkage disequilibrium with CD19 (GT)(15-18), may
      be associated with susceptibility to SLE in Japanese.

PMID- 12215899
TI  - Genetic linkage of systemic lupus erythematosus with chromosome 11q14 (SLEH1) in
      African-American families stratified by a nucleolar antinuclear antibody pattern.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease with complex
      genetics. We evaluated pedigrees multiplex for SLE that had an affected with
      antinucleolar antibodies to increase the homogeneity for genetic linkage
      analysis. We found a significant linkage effect on chromosome 11q14 at marker
      D11S2002 in African-American Pedigrees. This effect produced a maximum LOD score
      of 5.62 using a dominant inheritance model with 95% penetrance in males and 99%
      penetrance in females. The results were supported by multipoint linkage analysis.
      Fine mapping of the region with two additional markers within 6 cM of D11S2002
      further provided evidence of linkage in this region. Linkage at D11S2002, named
      SLEH1, was previously found in some of these same African-American pedigrees
      multiplex for SLE, but who were stratified by hemolytic anemia (Kelly et al,
      submitted). In conclusion, an important SLE susceptibility gene, SLEH1 at 11q14,
      is identified in African-Americans when stratifying pedigrees by antinucleolar
      autoantibodies.

PMID- 12215901
TI  - Association of angiotensin-converting enzyme polymorphisms with systemic lupus
      erythematosus and nephritis: analysis of 644 SLE families.
AB  - Angiotensin II is a strong candidate for the perpetuation of autoimmunity,
      nephritis and visceral damage in systemic lupus erythematosus (SLE). Our goal was
      to determine whether angiotensin-converting enzyme (ACE) gene polymorphisms are
      associated with SLE and/or lupus nephritis (LN). We genotyped 644 SLE patients
      and 1130 family members for three ACE gene polymorphisms: Alu insertion/deletion
      (I/D), 23949 (CT)(2/3) and 10698 (G)(3/4). All patients met the American College
      of Rheumatology (ACR) criteria for SLE, and all LN patients met ACR renal
      criteria and/or had biopsy evidence of LN. We used the
      transmission/disequilibrium test (TDT) to examine associations between each
      polymorphism and SLE, including Caucasian, non-Caucasian, and LN subgroups. We
      also examined transmission of haplotypes defined by these polymorphisms. The ACE
      I/D polymorphism was associated with SLE among non-Caucasians (61% transmission,
      P = 0.026) and the 23949 (CT)(2/3) polymorphism was associated with LN among non
      Caucasians (69% transmission, P = 0.014). Several haplotypes defined by these 2
      markers demonstrated strikingly increased transmission among non-Caucasians (81% 
      66% transmission, P = 0.0046 to 0.010). Due to the choice of study design and
      analytic method these results are unlikely to be due to population admixture. Our
      findings suggest that DNA sequence variation in the ACE gene influences the risk
      of developing SLE and LN.

PMID- 12215900
TI  - Genome scan stratified by the presence of anti-double-stranded DNA (dsDNA)
      autoantibody in pedigrees multiplex for systemic lupus erythematosus (SLE)
      establishes linkages at 19p13.2 (SLED1) and 18q21.1 (SLED2).
AB  - Anti-double-stranded DNA (anti-dsDNA) is arguably one of the most specific
      autoantibodies in systemic lupus erythematosus (SLE). This antibody is associated
      with more severe SLE and with glomerulonephritis. From 196 pedigrees multiplex
      for SLE, we selected those that had any SLE affected positive for anti-dsDNA by
      the Crithidia luciliae kinetoplast imunofluorescence assay. This stratification
      strategy tested the hypothesis that anti-dsDNA would identify a more genetically
      homogeneous group of pedigrees, in which previously undetected linkage effects
      could be established. A genome screen data for linkage to SLE was available at
      307 microsatellite markers for this selected group of 71 pedigrees: 37 European
      American, 29 African-American, and five others. The most significant results were
      obtained at 19p13.2 (LOD(max) = 4.93), named SLED1, in the 37 European-American
      pedigrees using a dominant model with mixed penetrances (92% for females and 49%
      for males) at 100% homogeneity (theta = 0). A second linkage effect, SLED2, was
      established in the 29 African-American pedigrees at 18q21.1 (LOD(max) = 3.40)
      using a recessive model with 100% penetrance (theta = 0.1). Parametric and non
      parametric multipoint analyses were performed, which provided further evidence
      and support of susceptibility genes residing in these regions. In conclusion, two
      powerful linkages have been detected with SLE based on the presence of anti
      dsDNA. These findings show SLE to be a richly complicated disease phenotype that
      is now ripe for important new discovery through a genetic approach.

PMID- 12215902
TI  - Characterization of the FcgammaRIIA promoter and 5'UTR sequences in patients with
      systemic lupus erythematosus.
AB  - FcgammaRIIA is a candidate gene involved in the predisposition to systemic lupus
      erythematosus (SLE). The presence of low binding alleles in patients with SLE is
      not sufficient to explain the lower phagocytic capacity observed in SLE patients.
      We considered the possibility that nucleotide polymorphisms in the FcgammaRIIA
      promoter that cause alterations in receptor expression might be present in SLE
      patients. In the present study, a 2.0 kb region of the human FcgammaRIIA 5'UTR
      from 20 normal donors and 53 SLE patients was examined. The results demonstrate
      that the sequence of the human FcgammaRIIA 5' region differs from the published
      sequence. Two novel SNPs have been identified in the distal region of the
      FcgammaRIIA promoter. The polymorphisms are present in both disease-free and SLE
      donors and do not associate with quantitative changes in FcgammaRIIa phagocytic
      function.

PMID- 12215903
TI  - Genomic organization of classical human low-affinity Fcgamma receptor genes.
AB  - The classical low-affinity Fcgamma receptor genes (FcgammaRIIA, B, C and
      FcgammaRIIIA, B) are located on chromosome 1q23, a region that shows strong
      linkage with human systemic lupus erythematosus (SLE) in several genome-wide
      scans, and family-based association between FcgammaRIIIA and SLE is now
      established. High homology among the Fcgamma receptor genes, however, has
      hampered further study of this region. We have used a human bacterial artificial
      chromosome (BAC) library to determine the order and orientation of these Fcgamma
      receptor genes and have sequenced the very highly homologous 5' region (including
      3.4 kb of the promoter and the 8 kb from exon 1 to exon 3) of the FcgammaRIIB and
      FcgammaRIIC genes to enable study of their unique single nucleotide polymorphisms
      (SNP). We have utilized these data to characterize a linked set of three coding
      region SNPs in the FcgammaRIIC exon 3 (EC1) that includes the stop codon SNP,
      which provides an important insight into natural killer cell function. Together,
      these data provide the basis for the study of additional SNPs in FcgammaR genes
      in SLE disease susceptibility.

PMID- 12215904
TI  - The genetics of systemic lupus erythematosus stratified by renal disease: linkage
      at 10q22.3 (SLEN1), 2q34-35 (SLEN2), and 11p15.6 (SLEN3).
AB  - Renal disease occurs in 40-75% of systemic lupus erythematosus (SLE) patients and
      significantly contributes to morbidity and mortality. We used two pedigree
      stratification strategies to explore the impact of the ACR renal criterion for
      SLE classification upon genetic linkage with SLE. In both we used SLE as the
      phenotype. First, we evaluated genome scan data from >300 microsatellite markers
      in the 75 pedigrees that had at least one SLE affected with the SLE renal
      criterion. A maximum-likelihood parametric model approach produced a maximum
      screening LOD score of 3.16 at 10q22.3 in the European-American (EA) pedigrees.
      The African-American (AA) pedigrees obtained a maximum screening LOD score of
      2.58 at 11p15.6. A multipoint sib-pair regression analysis produced P = 0.0000008
      in EA at 10q22.3 (SLEN1) and P = 0.000001 in AA at 2q34-35 (SLEN2). A second
      stratification strategy explored the renal criterion in 35 pedigrees with two or
      more SLE patients with renal disease and produced a LOD score of 3.34 at 11p15.6
      in AA (SLEN3). Sib-pair analysis in these 35 pedigrees revealed P = 0.00003 at
      4q13.1 in EA, P = 0.00003 at 11p13 and 0.00007 at 3q23 in AA. Thus, multiple
      genetic linkages are related to the renal criterion in SLE. Of the significant
      genetic linkages with SLE described herein, those at 10q22.3 in the EA pedigrees
      (SLEN1) and at 2q34-35 in the AA pedigrees (SLEN2) have not been previously
      described.

PMID- 12215905
TI  - Immunoglobulin kappa light chain gene alleles are not associated with primary
      Sjogren's syndrome.
AB  - The immunoglobulin kappa (Km) light chain gene is polymorphic and is believed to
      play a role in the pathology of infectious and autoimmune diseases. Polymorphisms
      within the constant region of the Km gene encode three alleles designated Km1,
      Km1,2 and Km3. Previous studies using serological detection of Km allotypes
      reported associations between specific Km allotypes, systemic lupus erythematosus
      and the presence of anti-La antibodies, yet these findings were not confirmed in
      other studies. In order to more precisely define any associations between Km
      alleles and anti-Ro/La antibodies we used the polymerase chain reaction and
      restriction fragment length polymorphisms for Km genotyping in a large cohort of
      patients with primary Sjogren's syndrome (SS). No associations were observed
      between specific Km alleles and primary SS when compared with a control
      population, nor within serologically defined subsets of SS patients. We conclude
      that Km alleles are not associated with primary SS or the Ro/La autoantibody
      response.

PMID- 12215906
TI  - Inactivation of the Fas gene by Alu insertion: retrotransposition in an intron
      causing splicing variation and autoimmune lymphoproliferative syndrome.
AB  - Mutations in the Fas (apo-1, CD95) gene result in autoimmune lymphoproliferative
      syndrome (ALPS). These mutations are dominated by small deletions and point
      mutations that result in splicing errors or missense changes. We report here a
      novel mutation caused by retrotransposon insertion, which results in loss of exon
      8 and ALPS. A father and son suffering from recurrent lymphadenopathy were
      examined for resistance to Fas-mediated apoptosis. A functional defect was
      detected and RT-PCR analysis revealed two different copies of Fas mRNA, one
      normal and a second shorter version lacking exon 8. DNA analysis of the genomic
      region between exons seven and nine in the longer copy revealed two PCR products,
      one being 331 base pairs (bp) longer than expected. Sequencing revealed that
      intron 7 had undergone an insertion event with an Alu element (99.31% homology
      with Alu-Sb1) of 331 bp. This element included a 34-bp Poly A tract that was
      flanked on each side by a perfect 17 bp direct duplication of the target site.
      Both patients were heterozygous for the mutated allele that produced Fas mRNA
      lacking exon 8, although not due to loss of a splice junction. The structure of
      the insertion suggests that the Alu element may have integrated by
      retrotransposition, and represents the first report of a retrotransposon causing
      ALPS.

PMID- 12215907
TI  - The genetics of systemic lupus erythematosus: putting the pieces together.
AB  - With lambda(s) estimates of 10 to 20 and other evidence of familial aggregation,
      as well as a monozygotic twin concordance rate >20, systemic lupus erythematosus
      (SLE) would appear to be a very promising phenotype using modern genetic
      approaches. Indeed, genetic associations are already known at numerous candidate
      loci including various HLA alleles, complement component genes, Fcgamma
      receptors, and others, and murine genetic studies of lupus models have provided
      additional candidate genes and potential syntenic linkages to evaluate in man.
      The completed genetic linkage studies performed on various collections of
      pedigrees multiplex for SLE have identified 60 susceptibility loci with varying
      degrees of evidence for linkage in man. Seven of these meet or exceed the
      threshold for significant linkage (LOD > or = 3.3 or P < or = 0.00005) at 1q22
      23, 1q41, 2q37, 4p16, 6p21-11, 16q13 and 17p13. In addition, these linkages
      usually dominate in one ethnicity or another, suggesting that the responsible
      polymorphisms, once identified, will also vary by ethnicity. Evidence that these
      linkages can be reproduced range from outright independent confirmation (1q41,
      4p16 and 6p21) to additional suggestive evidence in the genomic region of the
      purported linkage (1q22-23 and 2q37). The results now available suggest that
      human lupus genetics are robust and that gene identification should be possible
      using existing genetic approaches and technologies.

PMID- 12215908
TI  - A genetic marker within the CD44 gene confirms linkage at 11p13 in African
      American families with lupus stratified by thrombocytopenia, but genetic
      association with CD44 is not present.
AB  - Systemic lupus erythematosus (SLE) is complicated from both a clinical and
      genetic standpoint. We have stratified SLE families by the presence of
      thrombocytopenia, which is associated with increased mortality among SLE
      patients, and found genetic linkage at chromosome 11p13 in African-American
      families. In the present study we have evaluated CD44, a gene very close (0.5 cM)
      to the peak LOD score marker, as a candidate gene. Using a newly identified short
      DNA repeat within the CD44 gene, we find a LOD score of 2.7, which confirms
      linkage within this genetic interval. However, using a panel of four single
      nucleotide markers spanning the CD44 gene, we find no genetic association with
      SLE. Therefore, these data further suggest an SLE susceptibility gene at 11p13,
      but also imply that an ancestral mutation in the CD44 gene does not account for
      the linkage.

PMID- 12215909
TI  - [Updated recommendations on specific immunotherapy].

PMID- 12215910
TI  - [Shoulder the expenses for patients suffering from multirefractory pulmonary
      tuberculosis].

PMID- 12215911
TI  - [Onset of action of formoterol in patients with moderate to severe, partially
      reversible airflow obstruction assessed by bodyplethysmography].
AB  - BACKGROUND: Formoterol is a long acting beta2-agonist used for the treatment of
      obstructive airway diseases. Compared with Salmeterol, Formoterol has a rapid
      onset of bronchodilation. There are only scant data regarding the comparative
      onset of action using bodyplethysmography in moderate to severely obstructive
      patients. METHODS: In a mono-center, single-blinded parallel group study 60
      patients (age: 61.9 +/- 12.8 years, 65 % male) with moderate to severe (mean
      FEV(1) 40.6 +/- 15.3 % of predicted), partially reversible (FEV(1) post
      bronchodilator > 15 % from baseline) airway obstruction were treated with either
      formoterol 12 microg bid or salmeterol 50 microg bid over a period of two weeks.
      Onset of action was measured by airway resistance (sRaw) before and after two
      weeks of treatment. RESULTS: Compared with Salmeterol, Formoterol had a
      significantly faster onset of action (10 % decrease of Raw) at baseline (F: 1.4
      +/- 0.9 vs. S: 15.1 +/- 34.5 min., p < 0.0001) and after two weeks of treatment
      (F: 6.2 +/- 21.6 vs. S: 51 +/- 135 min., p < 0.0001). Morning FEV(1) improved
      similarily during treatment in both study groups, when compared with baseline
      lung function (F: 1.38 +/- 0.64 vs. 1 +/- 0.41 l; S: 1.43 +/- 0.67 vs. 1 +/- 0.4
      l, p < 0.05, both comparisons). Both treatments were well tolerated. CONCLUSION:
      Formoterol produces a rapid improvement of airway resistance in patients with
      moderate to severe, partially reversible airway obstruction. The onset of
      bronchodilation was significantly faster for Formoterol compared with Salmeterol.
      Both drugs improved lung function similarily after two weeks of treatment. It is
      important to distinguish beta2-agonists not only into short- and long-acting but
      also into fast- and slow-acting.

PMID- 12215912
TI  - [Effects of an optimized exercise therapy on physical performance of patients
      with cystic fibrosis].
AB  - Regular exercise training can increase the physical performance of patients with
      cystic fibrosis (CF). However, training is often hampered by negative factors
      such as infections, lack of time, etc. The aim of the present study was to
      investigate the effects of a 3-week-training-program performed under favourable
      conditions on physical performance and lung function of CF-patients: 17 patients
      daily trained at least 2,5 h under suspicious conditions at a sport hotel in
      Israel (Eilat). During the entire 3 weeks a comprehensive care was applied to the
      patients including intensive physical therapy and nutrition adapted to the
      individual demands. Testings of lung function and cycle ergometry ramp tests were
      performed a week before and after the training program. Additional control
      measurements were taken 7 months post training. After the 3-week-training vital
      capacity and FEV1 were increased by 7 % and 6 % (p > 0.05). The results of the
      cycle ergometry showed bigger and significant improvements in the maximal values
      of power (12 % - 20 %), oxygen uptake and ventilation. This findings were also
      valid for the submaximal exercise range indicated by a slower heart rate slope
      and a lower aerobic-anaerobic threshold. The present results suggest, that
      relatively large increases in physical performance can be obtained by short, but
      intensive exercise training including a comprehensive care.

PMID- 12215913
TI  - Fire eater's risk: lipoid pneumonia following aspiration of a liquid hydrocarbon
      mixture.
AB  - Acute aspiration of a liquid hydrocarbon mixture by fire eaters may cause severe
      lipoid pneumonia. The toxic effect of ingested hydrocarbon chains depends on
      their length and biophysical qualities. We report the case of a patient who
      accidentally aspirated a hydrocarbon liquid resulting in a lipoid pneumonia. The
      pathomechanism, diagnostic work-up, and the therapeutic approach are discussed.

PMID- 12215914
TI  - [The state of tuberculosis in Germany in 2000].
AB  - Tuberculosis is one of the leading infectious diseases globally besides HIV/AIDS
      and malaria. Around 8 million people per year develop active tuberculosis, of
      whom 2 million eventually die of the disease. Of special importance to Germany is
      the epidemiologic situation in the former Soviet Union, where new infections are
      rising steeply. This region is also a hot spot for the development of multidrug
      resistant tuberculosis. In 2000, the WHO registered already 273 000 cases of
      multidrug-resistant tuberculosis worldwide. In Germany the tuberculosis situation
      is stable. 9 064 persons (910 less than 1999) had tuberculosis in the year 2000.
      5 271 cases were tuberculosis of the respiratory tract with detection of
      Mycobacteria tuberculosis. In 2 264 cases registered as tuberculosis of the
      respiratory tract, Mycobacteria tuberculosis could not be detected. 1 529 persons
      developed extrapulmonary tuberculosis. The highest incidences were found among
      the elderly. One third of the tuberculosis patients were born outside Germany.
      Resistance to antituberculous drugs also increased slowly in Germany. A study of
      the DZK, although with small numbers, demonstrated an increase of multidrug
      resistant tuberculosis from 1.2 % (1996) to 1.7 % (2000), which also influenced
      the treatment outcome. With rising resistance rates, the treatment success
      decreased from 77.5 % in fully susceptible to 59.5 % in multidrug-resistant
      cases.

PMID- 12215915
TI  - [Six-minute walk test in chronic lung and heart disease - technical aspects,
      interpretation, limitations].

PMID- 12215917
TI  - [Scandal drug politics].

PMID- 12215918
TI  - [Does maintenance treatment reduce the mortality rate of opioid addicts?].
AB  - Reduction of mortality is a basic goal of methadone maintenance treatment (MMT)
      for opioid addicts. During the last years, however, there have been reports about
      drug related deaths of MMT patients and of untreated drug addicts who had
      consumed illegally purchased methadone. To evaluate the supposed beneficial
      effect of MMT on mortality, data from a multicentre trial in the German state of
      North Rhine-Westphalia were analysed. 244 patients with long histories of opioid
      addiction and previous failures in at least two abstinence oriented treatments
      were observed for at least four years and up to eight years after admission to
      MMT. With 32 deaths out of 244 participants, the mortality rate for the whole
      sample was 2.5 % p.a. This rate is not remarkably different from estimations for
      opioid addicts in general. However, addicts in continuous maintenance treatment
      had a mortality rate of only 1.6 % p.a., in contrast to a rate of 8.1 % p.a. for
      addicts who had left treatment. These results are supported by other long-term
      studies with large patient samples. Therefore it is concluded that methadone
      maintenance treatment is a measure to reduce the mortality in opioid addicts.
      Attainment of this goal is threatened, however, by deviations from safety
      standards, especially if take-home privileges are granted too widely.

PMID- 12215919
TI  - [Pharmacological agents for treatment of paraphilias and hypersexual disorders].
AB  - We review the indications, modes of action, effectiveness, side effects, legal
      and ethical aspects of pharmacological agents which reduce sexual desire. It
      needs to be emphasized that these agents - regardless of their indication -
      should never be used without concomitant psychotherapy. Nevertheless, in this
      review we focus on pharmacotherapy, because it can be an important part of the
      therapeutic procedure and appropriate knowledge is required. A part of the review
      pertains to the therapy of male adolescents.

PMID- 12215920
TI  - [Dementias with Lewy bodies].
AB  - Dementias with Lewy bodies are no rare cause of cognitive and motor impairments
      in old age. Neuropathologically, they must be distinguished into diffuse Lewy
      body disease resp. dementia with Lewy bodies, Parkinson's disease with
      concomitant Alzheimer's pathology, and the Lewy body variant of Alzheimer's
      disease according to extent and concomitant pathology. The most reliable
      diagnostic features of dementia with Lewy bodies are fluctuating disturbances of
      cognition and consciousness, visual disorders (hallucinations, visuoperceptive
      and visuoconstructive impairments), and early extrapyramidal signs of the
      hypokinetic-rigid type with a propensity to frequent falls. The pertinent
      diagnostic criteria are the consensus criteria according to McKeith et al.
      Additional contributions are to be expected by functional neuroimaging (SPECT,
      PET) and CSF examination (homovanillic acid). However, even assuming the most
      favorable conditions a diagnostic accuracy of 85 % is presently hard to achieve.
      Particularly, as is demonstrated using a case example, reliable antemortem
      diagnosis of Lewy body variant of Alzheimer's disease is hardly possible.
      Clinically, this group of diseases is important, since increased neuroleptic
      sensitivity must be taken into account and modern central cholinergic agents seem
      to be a promising therapeutic option.

PMID- 12215921
TI  - [The concept of anniversary reaction - an explanation for the onset of
      depression].
AB  - In this contribution, the concept of anniversary reaction is explained and
      elucidated by a paradigmatic case-report. The influence of a certain date, e.g.
      birthday, on mortality is epidemiologically well proven. The psychoanalytical
      comprehension of anniversary reaction emphasizes the significant coherence to a
      biographical trauma. An anniversary reaction emerges on a specific date or age of
      life that reminds and actualises the conflict attached to the trauma. The
      anniversary reaction may appear in the shape of a psychic or an organic disease.
      In the case described, the anniversary reaction emerged on the anniversary of the
      death of the partner of life that had initially been followed by pathological
      mourning.

PMID- 12215923
TI  - [Clinical research in Germany--improvements are necessary and possible].

PMID- 12215924
TI  - [Do polymorphisms of the SDF1 and CCR2b genes modify the course of hepatitis C or
      HIV/HCV co-infection?].
AB  - BACKGROUND AND OBJECTIVE: Complementary to the CCR5-Delta32 mutation
      polymorphisms in the genes of CCR2b (CCR2b-V64 I) and stromal derived factor
      (SDF)-1 (SDF-1 3'A) affect the course of the human immunodeficiency virus (HIV)
      infection. While the CCR5-Delta32 mutation is also increased in chronic hepatitis
      C virus (HCV) infection it is unclear, whether the CCR2b-V64 I and the SDF-1 3'A
      polymorphisms also are associated with chronic HCV infection. METHODS: We
      analyzed the frequencies of the CCR2b-V64I and SDF1 - 3'A mutation in patients
      with HIV/HCV coinfection (n = 130), HIV infection (n = 105), HCV infection (n =
      153) and 112 healthy blood donors. We stratified each group into homozygous
      mutations, heterozygous mutations and homozygous wild types, respectively. The
      resulting subsets were compared with respect to HIV and HCV loads, CD4 and CD8
      cell counts. RESULTS: The mutant SDF1 - 3'A allele was found at 20.3 % frequency
      in patients with HCV infection and at 20.4 % frequency in patients with HIV/HCV
      coinfection, respectively. It was present in 27.1 % of the patients with HIV
      infection and 27.9 % of the healthy controls (not significant). The number of SDF
      1 3) A homozygous patients was highest in patients with HIV/HCV coinfection and
      significantly different compared to the Hardy-Weinberg equilibrium (p = 0.010,
      chi (2) = 9.15). However, CD4- and CD8-cell counts or viral loads were not
      affected by this mutation. The frequency of the CCR2b-V64 I allele was similar in
      all patient groups. However, CCR2b-V64 I heterozygous patients showed HIV loads
      that were threefold lower than in CCR2b wildtype patients (22.9 x 103 vs. 6.4 x
      103 copies/ml, not significant). Furthermore, hepatitis C viral loads were
      reduced roughly by 30 %. CONCLUSION: These results suggest that the SDF1 - 3'A
      and CCR2b-V64I mutations do not affect the course of HCV and HIV/HCV infection in
      the same manner as does the CCR5-Delta32 mutation.

PMID- 12215925
TI  - [Endemic celiac sprue and Hodgkin's disease in a 72-year-old patient].
AB  - HISTORY AND CLINICAL FINDINGS: A 72-year-old man was admitted with diarrhea, loss
      of weight and anemia. The diarrhea started after antibiotic treatment of a
      pneumonia and persisted for 6 months at admission. Monoclonal gammopathy was
      found on external examination. INVESTIGATIONS AND DIAGNOSIS: The work-up yielded
      iron deficiency anemia, monoclonal gammopathy (IgG kappa) and elevated polyclonal
      IgA due to Gliadin- and endomysium-antibodies. Duodenal mucosa biopsies showed
      villous atrophy and increased intraepithelial lymphocytes. Celiac disease was
      diagnosed. Unexpectedly, mediastinal lymphomas were found and the concomitant
      diagnosis of Hodgkin's disease was made. TREATMENT AND COURSE: On gluten free
      diet all symptoms of malabsorption resolved. Therapy for the Hodgkin lymphoma
      with chemotherapy was initiated. As Bleomycin associated lung disease occurred
      during therapy, radiotherapy was not administered. A complete remission could be
      achieved. CONCLUSIONS: The association of celiac disease and malignancy is well
      known. The pathogenesis is not fully understood, but a correlation between the
      duration of gluten exposure and the rate of malignancy was found. Thus, the
      chronic immunologic stimulation might also have contributed to the development of
      Hodgkin's disease in our patient, which to date has been reported only
      anecdotally.

PMID- 12215926
TI  - [Cholestatic liver diseases: diagnosis and therapy of primary biliary cirrhosis].

PMID- 12215927
TI  - [Cholestatic liver diseases: diagnosis and therapy of primary sclerosing
      cholangitis].

PMID- 12215930
TI  - [Palliative therapy of inoperable cholangiocarcinoma].

PMID- 12215931
TI  - [Chronic hepatitis C virus infection: always treat!--Pro].

PMID- 12215932
TI  - [Chronic hepatitis C virus infection: always treat!--Contra].

PMID- 12215933
TI  - ["Good digestion is better than a million dollars" (Theodor Fontane). From enema
      to modern pancreas research].

PMID- 12215934
TI  - [New facts on the risks of aspiration?].

PMID- 12215935
TI  - [A child with a full stomach has to be anaesthesized].
AB  - In the present paper the problem of giving anaesthesia to a child with a full
      stomach is discussed using a case report. Children are not by nature more in
      danger of aspiration than grown-ups. Even the higher risk of aspiration in
      children with a full stomach, which seems plausible, is not proven in all
      published studies on this subject. Since there is a more or less large amount of
      residual gastric secrete even 6 - 10 hours after the accident, due to stress or
      opioids, and prophylaxis against aspiration must be taken in any case, narcosis
      for the emergency treatment of these children can be applied immediately at the
      same risk. Rapid sequence induction is the world-wide standard as prophylaxis
      against aspiration today. Should aspiration happen, bronchoscopic draining is the
      main measure. Artificial ventilation is not a cogent measure, if the airway is
      free as far as the visible segmental bronchus and there are no disruptions in the
      respiratory exchange.

PMID- 12215936
TI  - [Risk predictors, scoring systems and prognostic models in anesthesia and
      intensive care. Part I: anesthesia].
AB  - Risk predictors and scoring systems are commonly used in medicine to provide a
      reliable and objective estimation of disease prognoses, probability of adverse
      events and outcome. Furthermore, they were designed to classify severity of
      illness or the course of diagnostic and therapeutic interventions and to perform
      a risk stratification for scientific studies in a standardized way. In quality
      management and cost control, scoring systems and predictors are used for risk
      adjustment and evaluation of care performance. The aim of this review article was
      to describe common risk indices and scoring systems in anesthesia (part I) and
      intensive care (part II), and to point out their possible benefits and
      limitations. Different scoring systems and classifications are available to
      stratify perioperative risk and adverse events in anesthesia. Especially in
      cardiac surgery, an increasing interest in risk-adjusted outcome studies led to
      the modeling and validation of different prognostic systems for postoperative
      morbidity, mortality and length of stay. Furthermore, there are scoring-systems
      for special events, such as difficult laryngoscopy or postoperative nausea and
      vomiting (PONV). Risk check lists and risk indices are superior to the ASA
      classification of physical status in providing more exact results and the
      possibility of statistic risk calculation. Nevertheless, they are not frequently
      used in clinical routine. Because of its simplicity and easy handling the ASA
      classification has worldwide popularity and recent studies demonstrated at least
      equal prognostic performance.

PMID- 12215937
TI  - [Dolasetron reduces pain on injection of propofol].
AB  - OBJECTIVE: Pain on injection is a well known side-effect of propofol. The present
      study was designed to assess the efficacy of dolasetron, a 5-HT 3 -antagonist, in
      prophylaxis of pain on injection of propofol compared with lidocaine and placebo.
      METHODS: Prospective, randomised, double-blinded study including 150 patients
      randomly assigned to one of three groups: Group A received 12.5 mg dolasetron,
      group B 40 mg lidocaine and group C saline 0.9 % as placebo. After occluding the
      venous drainage the test medication was given. The occlusion was released after 1
      min and 2.0 mg/kg Propofol was administered over a period of 30 sec. The patients
      were asked whether they felt any pain during the administration. Pain on
      injection was judged by using a four-point scale. RESULTS: Incidence of pain on
      injection as well as the severity of pain was significantly reduced by lidocaine
      (62 % pain free) compared with placebo (28 %). Severity, but not incidence of
      pain on injection was significantly reduced by dolasetron (50 %) compared with
      placebo. There was no significant difference between dolasetron and lidocaine.
      CONCLUSION: Dolasetron and lidocaine were effective in preventing pain of
      injection secondary to propofol.

PMID- 12215938
TI  - [Emergency intubation with magill tube, laryngeal mask and esophageal tracheal
      combitube in a training-course for emergency care physicians].

PMID- 12215939
TI  - New aspects in mass casualties.

PMID- 12215940
TI  - [Germs employed as biological weapons].

PMID- 12215942
TI  - [New scenarios in major accidents--Use and adaption of current concepts to ward
      off damage].

PMID- 12215943
TI  - [Current safety standing and concepts for the city of Bielefeld].

PMID- 12215944
TI  - [Intraoperative hyperkalemia - initial sign of an incipient compartment
      syndrome?].
AB  - We report the case of a 50 years old male patient who underwent an elective
      resection of the rectum in the Lloyd-Davis-position. During the surgery, first
      endoscopically and then by open laparatomy, which lasted 7.5 hours and the
      following postoperative time, plasma potassium concentration continuously
      increased up to 6.7 mval/l. On the first postoperative day, a compartment
      syndrome of the right lower limb was diagnosed.

PMID- 12215945
TI  - [Anesthesia in aortal surgery].

PMID- 12215946
TI  - Can the diagnosis of NSAID-induced or Hp-associated gastric ulceration be
      predicted from histology?
AB  - We studied the question whether NSAID/ASA-induced ulcerations can be identified
      in human gastric biopsy material on the basis of ischaemic necrosis. Biopsies of
      208 patients with gastric ulcers were assessed histologically. 29 patients were
      excluded from the study. NSAID/ASA ulcers were diagnosed when a homogeneous
      eosinophilic ischaemic necrosis was found. Helicobacter pylori-(Hp-) induced
      ulcers were diagnosed when non-homogeneous fibrinoid necrotic material containing
      granulocytes and cell debris was noted. The histological diagnosis was compared
      with the data on medication use, endoscopy and clinical history. 121 of the 179
      patients included had a medical history on NSAIDS/ASA. From the 60 patients
      taking NSAIDS/ASA with no histologic evidence of Hp all (100 %) were identified
      by the histology of the necrosis. From the 61 patients taking NSAID/ASA and
      histologic evidence of H. pylori 40 (66 %) were identified by histology. From the
      58 patients with no such medication 41 were Hp-positive and correctly identified
      by histology in 31 cases (76 %). The sensitivity of the histologic diagnosis of
      NSAID/ASA-induced ulceration was 85 %, and its specificity 53 %. The results of
      our study show that a high percentage of the NSAID/ASA-induced ulcers of the
      stomach can indeed be correctly diagnosed at histology. In conclusion the
      underlying aetiopathogenesis of gastric ulcerations (NASID/ASA vs. Hp) can be
      uncovered in a large proportion of patients based on histological examination.

PMID- 12215947
TI  - [Magnetic Resonance Imaging in diagnosis and follow-up of Crohn's Disease--Is
      conventional enteroclysis still necessary?].
AB  - A non-invasive diagnostic modality for differential diagnosis and detection of
      complications in inflammatory bowel disease (IBD) is desirable as alternative to
      invasive and troublesome endoscopy and conventional radiological methods.
      METHODS: 51 patients suspicious of inflammatory bowel disease (bloody diarrhoea,
      symptoms of stenosis, abdominal pain) were investigated consecutively according
      to a standardised protocol by magnetic resonance tomography (MRI). Also,
      endoscopy was performed dependent on clinical presentation. MRI findings were
      compared to clinical follow-up, percutaneous ultrasonography (US), endoscopy, and
      surgical findings. RESULTS: MRI confirmed diagnosis of Crohn's disease (CD) in
      more than 90 % of cases. In case of distinct lesions, all of these were detected
      by MRI in the small bowel and colon. Discreet inflammatory lesions were not seen
      regularly. Numerous findings in endoscopically inaccessible bowel segments were
      described by MRI, extraintestinal lesions (conglomerate, abscess, fistulae) were
      detected accurately. Altogether, MRI was superior to abdominal ultrasonography.
      CONCLUSION: In patients with distinct inflammatory bowel disease, and in
      detection of complications (abscess, fistulae), MRI appears as versatile, non
      invasive and accurate diagnostic instrument with therapeutical consequence.
      Endoscopy remains method of first choice for detection of discreet lesions and
      for histopathological diagnosis.

PMID- 12215948
TI  - Combination prophylaxis with Hepatitis B immunoglobulin and lamivudine after
      liver transplantation minimizes HBV recurrence rates unless evolution of
      pretransplant lamivudine resistance.
AB  - BACKGROUND: Survival rates of hepatitis B patients after liver transplantation
      improved significantly by introduction of passive immunoprophylaxis. Due to viral
      escape mutations recurrence still occurs, but recently a combination prophylaxis
      with hepatitis B immunoglobuline plus lamivudine is evaluated in transplant
      centers in terms of a further reduction of recurrence rates. PATIENTS AND
      METHODS: Between 1996 and 2000 a postoperative combination prophylaxis with HBIg
      and lamivudine was initiated in 44 HBsAg positive liver transplant recipients. In
      total 14 patients were HBV-DNA negative and 30 were HBV-DNA positive at the time
      of evaluation. In 22 HBV-DNA positive patients a pre-operative lamivudine
      treatment (150 mg/die) was started. Five of them developed pre-transplant
      lamivudine resistance with high viral replication (mean HBV-DNA prior to
      transplantation 728 +/- 219 pg/ml). In all patients passive immunoprophylaxis was
      started in the anhepatic phase with application of 10.000 units hepatitis B
      immunoglobuline. It was continued after seroconversion to HBsAg negativity with
      an aimed titer of more than 100 U/l and only stopped in case of HBV recurrence.
      Lamivudine was also continued indefinitely after liver transplantation. RESULTS:
      Overall recurrence rate in the 44 patients, including retransplantations and
      patients with pretransplant lamivudine resistance, was 11.5 % under combination
      prophylaxis. Recurrence was seen only in one of 39 patients (2.6 %) without
      preoperative lamivudine resistance, in contrast 4 out of 5 patients (80 %) with
      pre-existing lamivudine resistance suffered from early hepatitis B recurrence.
      The single patient without preoperative lamivudine resistance, who developed
      recurrence was pre-transplant HBV-DNA negative without lamivudine treatment, but
      a postoperative seroconversion to negative HBsAg could not be achieved. The
      overall 3 year patient survival rate was 91 % in the study population. One
      patient, who was retransplanted with preoperative lamivudine resistance, died 4.5
      months after retransplantation due to hepatitis B recurrence and sepsis, three
      other patients died for reasons not related to hepatitis B recurrence.
      Combination prophylaxis was well tolerated in all patients and no severe side
      effects were observed. CONCLUSION: Combination prophylaxis with hepatitis B
      immunoglobulin and lamivudine is safe and highly effective in prevention of HBV
      recurrence after liver transplantation, even in case of positive viral
      replication. In accordance with the results of other centers it should therefore
      be the standard regimen. However it fails in the majority of patients with
      preoperative evolution of YMDD mutations, in which the optimal management has to
      be determined yet. To minimize preoperative resistance formation universal
      preoperative antiviral treatment of HBV-DNA positive patients should be replaced
      by individualized indication for preoperative treatment.

PMID- 12215949
TI  - [Infection with fasciola hepatica causing elevated liver-enzyme results and
      eosinophilia - serologic and endoscopic diagnosis and therapy].
AB  - A 36 year old man was diagnosed with eosinophilia and elevated liver-enzyme
      levels in a preoperative routine laboratory testing. In the course of the
      evaluation we found high levels of Fasciola hepatica specific antibodies which
      lead to an ERC with biliary aspiration after choleretic stimulation. The bile
      showed Fasciola eggs and subsequently we recovered a parasite from the bile duct.
      Abdominal CT- and MRI-Scans showed lesions of the liver consistent with hepatic
      fascioliasis. Focussed patient's history revealed ingestion of contaminated
      watercress in Turkey as the most likely source of infection. For patients with
      elevated liver-enzymes of unknown etiology with eosinophilia or in combination
      with a congruent patient's history even without eosinophilia serologic studies of
      Fasciola hepatica seem to be advisable. We suggest an ERC with biliary aspiration
      to prove the diagnosis in case of positive results, if the prepatency period of 4
      months after the ingestion is over. Fasciola hepatica is rarely diagnosed in
      Germany probably due to the lack of awareness of the disease.

PMID- 12215950
TI  - Interstitial pneumonitis during combination therapy with interferon-alpha and
      ribavirin in a patient with chronic Hepatitis C.
AB  - After nine weeks of combination therapy with recombinant interferon-alpha and
      ribavirin for chronic hepatitis C a 62-year old woman complained of a dry cough
      and exertional dyspnea. An elevated erythrocyte sedimentation rate was noticed.
      Prior to treatment chest X-rays and physical examination revealed no pulmonary
      abnormalities. Inhalative steroids did not improve the symptoms and afer 12 weeks
      treatment chest X-ray and computed tomography showed bilateral reticonodular lung
      infiltration suggesting a diagnosis of interstitial pneumonitis. Cough and
      dyspnea resolved and abnormal lung shadows were reversible within two months
      following discontinuation of interferon-/ribavirin treatment. In the Japanese
      literature there are similar reports on pneumonitis occurring during high-dose
      IFN-alpha and concomitantly Chinese herbal medicine treatment. To our knowledge
      this is one of the first cases of interstitial pneumonitis due to combination
      therapy with IFN-alpha and ribavirin in chronic hepatitis C reported in the
      western world.

PMID- 12215951
TI  - Severe intestinal bleeding caused by intestinal metastases of a primary
      angiosarcome of the thyroid gland.
AB  - A 75 year old male presented with gastrointestinal bleeding after resection of
      both upper lobes of the lungs because of metastases. One year ago an angiosarcoma
      was the reason for a complete removal of the thyroid gland. In esophago-gastro
      duodenoscopy we found multiple hemorrhagically stained polyploids lesions in the
      postbulbar duodenum and jejunum. Colonoscopy showed isolated polyploid lesions of
      the right flexura. Because of persistent gastrointestinal bleeding a diagnostic
      laparotomy was done. Intraoperative intestinoscopy demonstrated multiple bleeding
      metastasis. To remove many of the bleeding lesions two longer intestinal segments
      of the jejunum and ileum were resected. The histology of the metastases showed
      arrangements of polygonal cells with prominent nucleoli and atypical mitosis.
      Immunohistochemistry identified CD 31, vimentin and factor VIII associated
      antigen. There was an erosion of the superficial intestinal mucosal cells with
      resulting hemorrhage; same histology had been found in the thyroid gland and the
      right upper lobe of lung. Eight days after surgery the patient died because of
      respiratory and circulatory insufficiency.

PMID- 12215952
TI  - [Tobacco associated gastrointestinal disorders: smoking cessation therapy - a
      task for gastroenterologists].
AB  - Tobacco smoking is an independent risk factor in the etiology of Crohn's disease,
      functional dyspepsia, GERD, chronic pancreatitis and gastrointestinal carcinomas
      (oesophagus, stomach, colon, pancreas and liver). The current knowledge of the
      effects of tobacco smoking on the gastrointestinal tract is summarised. Non
      smoking should be recommended to everybody as primary prevention against
      cardiopulmonary and gastrointestinal diseases. Despite lacking of clinical
      studies tobacco abstinence should be recommended as a secondary preventive
      therapy of Crohn's disease, functional dyspepsia, GERD and chronic pancreatitis
      because of epidemiological studies and pathophysiological considerations. All
      gastroenterologists should help patients with the above mentioned diseases to
      stop smoking. Evidence based methods of smoking cessation and methods suited to
      routine clinical care are presented. Pharmacological (nicotine replacement
      therapy) and psychological therapies (cognitive behavioural group therapies)
      should be adapted to the prior experiences of the patient, his stage of
      motivation to stop smoking and his co-morbidity. In refractory ulcerative colitis
      controlled tobacco smoking can be recommended to ex-smokers.

PMID- 12215953
TI  - TIPS or vasoconstrictors for the treatment of hepatorenal syndrome type 1--effect
      on survival?
AB  - HRS is a serious complication in patients with cirrhosis and ascites and
      associated with a poor prognosis unless liver transplantation can be performed.
      Two different types of HES are being differentiated according to the clinical
      presentation: while HRS type I is characterised by rapid deterioration of renal
      function indicated by a two-fold increase of serum creatinine to values above 2.5
      mg/dl or a decrease of creatinine clearance to values below 20 ml/min, HRS type
      II shows moderately increased serum creatinine above 1.5 mg/dl remaining stable
      over a longer period. The most prominent circulatory alterations in patients with
      chronic liver disease comprise portal hypertension and peripheral (mainly
      splanchnic) arterial vasodilation. This leads to a decreased centrally effective
      blood volume in cirrhotic patients. As a consequence, activation of sodium- and
      volume-retaining neurohumoral systems such as the renin-angiotensin-aldosterone
      system and the sympathetic nervous system and a non-osmotic release of arginine
      vasopressin can be observed. These neurohumoral alterations induce renal sodium
      and water retention which are responsible for accumulation of ascites and
      deterioration of renal function. Recent therapeutic strategies of the hepatorenal
      syndrome take into account these pathophysiologic considerations: whereas the
      transjugular intrahepatic portosystemic shunt lowers portal hypertension,
      infusion of vasoactive drugs increases systemic vascular resistance in cirrhotic
      patients. Several uncontrolled trials have reported a positive effect of these
      strategies on renal function. The present analysis of combined data from these
      reports shows that this positive effect on renal function also may improve
      survival of patients with HRS type I.

PMID- 12215954
TI  - [Long term survival after pancreatic resection for pancreatic adenocarcinoma].

PMID- 12215955
TI  - [VEGF-C, VEGF-D and VEGF-receptor 3: novel key regulators of lymphangiogenesis
      and cancer metastasis].

PMID- 12215956
TI  - Red blood cell profile of elite olympic distance triathletes. A three-year follow
      up.
AB  - The purpose of this study was to monitor general and individual changes in
      hematological variables during long-term endurance training, detraining and
      altitude training in elite Olympic distance triathletes. Over a period of three
      years, a total of 102 blood samples were collected in eleven (7-male and 4
      female) elite Olympic distance triathletes (mean +/- SD; age = 26.4 +/- 5.1 yr;
      VO(2) max = 67.9 +/- 6.6 ml/min/kg) for determination of hemoglobin (Hb),
      hematocrit (Hct), red blood cell count (RBC), Mean corpuscular hemoglobin (MCH),
      Mean corpuscular hemoglobin content (MCHC), Mean corpuscular volume (MCV) and
      plasma ferritin. The data were pooled and divided into three periods; off-season,
      training season and race season. Blood samples obtained before and after altitude
      training were analyzed separately. Of all measured variables only RBC showed a
      significant decrease (p < 0.05) during the race season compared to the training
      season. Hematological values below the lower limit of the normal range were found
      in 46 % of the athletes during the off-season. This percentage increased from 55
      % during the training season to 72 % of the athletes during the race season.
      Hemoglobin and ferritin values were most frequently below the normal range. There
      was a weak correlation between Hb levels and VO(2) max obtained during maximal
      cycling (r = 0.084) and running (r = 0.137) tests. Unlike training at 1500 m and
      1850 m, training at an altitude of 2600 m for three weeks showed significant
      increases in Hb (+ 10 %; p < 0.05), Hct (+ 11 %; p < 0.05) and MCV (+ 5 %; p <
      0.05). Long-term endurance training does not largely alter hematological status.
      However, regular screening of hematological variables is desirable as many
      athletes have values near or below the lower limit of the normal range. The data
      obtained from altitude training suggest that a minimum altitude (>2000 m) is
      necessary to alter hematological status.

PMID- 12215957
TI  - Effects of age and recovery duration on peak power output during repeated cycling
      sprints.
AB  - The aim of the present study was to investigate the effects of age and recovery
      duration on the time course of cycling peak power and blood lactate concentration
      ([La]) during repeated bouts of short-term high-intensity exercise. Eleven
      prepubescent boys (9.6 +/- 0.7 yr), nine pubescent boys (15.0 +/- 0.7 yr) and ten
      men (20.4 +/- 0.8 yr) performed ten consecutive 10 s cycling sprints separated by
      either 30 s (R30), 1 min (R1), or 5 min (R5) passive recovery intervals against a
      friction load corresponding to 50 % of their optimal force (50 % Ffopt). Peak
      power produced at 50 % Ffopt (PP50) was calculated at each sprint including the
      flywheel inertia of the bicycle. Arterialized capillary blood samples were
      collected at rest and during the sprint exercises to measure the time course of
      [La]. In the prepubescent boys, whatever recovery intervals, PP50 remained
      unchanged during the ten 10 s sprint exercises. In the pubescent boys, PP50
      decreased significantly by 18.5 % (p < 0.001) with R30 and by 15.3 % (p < 0.01)
      with R1 from the first to the tenth sprint but remained unchanged with R5. In the
      men, PP50 decreased respectively by 28.5 % (p < 0.001) and 11.3 % (p < 0.01) with
      R30 and R1 and slightly diminished with R5. For each recovery interval, the
      increase in blood [La] over the ten sprints was significantly lower in the
      prepubescent boys compared with the pubescent boys and the men. To conclude, the
      prepubescent boys sustained their PP50 during the ten 10 s sprint exercises with
      only 30 s recovery intervals. In contrast, the pubescent boys and the men needed
      5 min recovery intervals. It was suggested that the faster recovery of PP50 in
      the prepubescent boys was due to their lower muscle glycolytic activity and their
      higher muscle oxidative capacity allowing a faster resynthesis in
      phosphocreatine.

PMID- 12215958
TI  - L-arginine reduces exercise-induced increase in plasma lactate and ammonia.
AB  - To investigate the effect of L-arginine supplementation (L-ARG) on physiological
      and metabolic changes during exercise, we determined in a double-blind study the
      cardiorespiratory (heart rate, oxygen consumption (VO(2)) and carbon dioxide
      production (VCO(2)) and the metabolic (lactate and ammonia) responses to maximal
      exercise after either an intravenous L-ARG hydrochloride salt or placebo load in
      8 healthy subjects. Exercise-induced increases in heart rate, VO(2) and VCO(2)
      were not significantly different after L-ARG or placebo. By contrast, peak plasma
      ammonia and lactate were significantly decreased after L-ARG load (60.6 +/- 8.2
      vs. 73.1 +/- 9.1 micro mol x l(-1), p < 0.01 and 7.1 +/- 0.7 vs. 8.2 +/- 1.1 mmol
      x l(-1), p < 0.01, for ammonia and lactate, respectively). Plasma L-citrulline
      increased significantly during exercise only after L-ARG load, despite a
      concomitant decrease in plasma L-ARG. Furthermore, a significant inverse
      relationship was observed between changes in lactate and L-citrulline
      concentrations after L-ARG load (r = -0.84, p = 0.009). These results demonstrate
      that intravenous L-ARG reduces significantly exercise-induced increase in plasma
      lactate and ammonia. Taken together, the specific L-citrulline increase and the
      inverse relationship observed between L-citrulline and plasma lactate after L-ARG
      might support that L-ARG supplementation enhances the L-arginine-nitric oxide
      (NO) pathway during exercise.

PMID- 12215959
TI  - Muscular efficiency during arm cranking and wheelchair exercise: a comparison.
AB  - The present study was performed to compare various individual muscular efficiency
      indices, i. e., gross (GE), net (NE), work (WE), and delta (DE), during arm
      cranking ergometer (ACE) and wheelchair ergometer (WERG) exercise at the same
      relative exercise intensities. Following a maximal test on both the ACE and WERG,
      15 able-bodied subjects completed 4 submaximal bouts at 0, 40, 55 and 70 % of the
      mode-specific VO(2) peak. The peak power output and VO(2) values were
      significantly higher with ACE than WERG maximal exercise. As a consequence, the
      power output imposed during WERG submaximal bouts was significantly lower
      compared to ACE submaximal bouts. ACE exercise was found to elicit a
      significantly higher (p < 0.001) VO(2) (16 to 28 vs 14 to 23 ml x min(-1) x kg(
      1)), GE (9 to 11 vs 6 to 9 %) and NE (14 to 13 vs 10 to 11 %) compared to WERG
      exercise at power output from 40 to 70 % VO(2) peak, respectively. However, WE
      (17 to 15 vs 17 to 14 % at 40 to 55 % VO(2)peak) and DE (12 to 13 vs 12 to 12 %
      at Delta 40 - 55 % to Delta 55 - 70 % VO(2) peak) values were similar between ACE
      and WERG exercise. The lower GE and NE observed during WERG compared to ACE
      exercise could be explained by the biomechanical disadvantages of the hand-rim
      WERG pattern movement. These findings also supported that the different indices
      of efficiency influenced the interpretation of the comparison between ACE and
      WERG propulsion.

PMID- 12215960
TI  - Improvement of cognitive function by mental and/or individualized aerobic
      training in healthy elderly subjects.
AB  - The aim of this study was to compare the effects of aerobic and mental training
      on cognitive function and to determine if the association of the two techniques
      shows better results. Thirty-two healthy elderly subjects (60 - 76 years) were
      assigned to one of four groups: aerobic training, mental training, combined
      aerobic and mental training and a control group. All subjects took two cognitive
      tests and an incremental exercise test before and after the training period. The
      intensity of exercise was individualized at the heart rate corresponding to the
      ventilatory threshold of each subject. After two months, the control group showed
      no alteration in physiological and cognitive variables. After the training
      period, the results showed a significant improvement in VO(2)max (F = 4.45, DF =
      1, p < 0.05) of 12 % and 11 % in aerobic training and combined aerobic and mental
      training groups, respectively. Logical memory (F = 4.31, DF = 1, p < 0.05), as
      well as paired associates learning scores (F = 5.47, DF = 1, p < 0.05) and memory
      quotient (F = 6.52, DF = 1, p < 0.01) were significantly improved in the three
      trained groups. The mean difference in memory quotient between pre and post
      training was significantly higher in the combined aerobic and mental training
      group compared to aerobic training or mental training groups (F = 11.60, DF = 3,
      p < 0.001). We conclude that the specific aerobic training and mental training
      used in this study could induce the same degree of improvement in cognitive
      function and that combined training seemed to lead to greater effects than either
      technique alone.

PMID- 12215961
TI  - Training intensity influences leptin and thyroid hormones in highly trained
      rowers.
AB  - Leptin (L) is associated with body-weight-regulating and adipostatic functions.
      Its receptors also may be found centrally. Thyroid hormones regulate metabolic
      processes mainly by binding at peripheral receptors. Aim of this study was to
      show if there is a link between those central and peripheral regulation systems
      and to investigate the influence of different training intensities on L and the
      hypothalamic-thyroid-axis (HTA) in highly trained rowers. Six rowers (18.9 +/-
      2.6 y; BMI 22.8 +/- 2.1 kg/m (2)) undertook high intensity resistance training
      (RT) for three weeks followed by three weeks of endurance training (ET). After
      each training cycle the subjects had one week for recovery (R1, R2). Blood
      samples were taken before and at the end of RT, R1, ET and R2. L, thyroid
      stimulating hormone (TSH), free T3 (fT3) and free T4 (fT4) were measured. After
      RT, a significant reduction in L, TSH and fT3 was found (p < 0.05). fT4 was
      unchanged. L remained decreased until the end of R1. After ET, a significant
      increase of TSH was found. L correlated to basal TSH levels (r = 0.49, p = 0.006)
      during R. BMI and body fat were unchanged throughout the study and were not
      correlated with hormonal levels. We speculate a high energy flux during
      intensified training (RT) caused the decrease of L and the HTA, independent of
      BMI or body fat. Thus, we conclude a depression of L and HTA is associated with
      training intensity.

PMID- 12215962
TI  - Oxygen uptake in whole-body vibration exercise: influence of vibration frequency,
      amplitude, and external load.
AB  - Vibration exercise (VbX) is a new type of physical training to increase muscle
      power. The present study was designed to assess the influence of whole-body VbX
      on metabolic power. Specific oxygen uptake (sVO(2)) was assessed, testing the
      hypotheses that sVO(2) increases with the frequency of vibration (tested in 10
      males) and with the amplitude (tested in 8 males), and that the VbX-related
      increase in sVO(2) is enhanced by increased muscle force (tested in 8 males).
      With a vibration amplitude of 5 mm, a linear increase in sVO(2) was found from
      frequencies 18 to 34 Hz (p < 0.01). Each vibration cycle evoked an oxygen
      consumption of approximately 2.5 micro l x kg(-1). At a vibration frequency of 26
      Hz, sVO(2) increased more than proportionally with amplitudes from 2.5 to 7.5 mm.
      With an additional load of 40 % of the lean body mass attached to the waist,
      sVO(2) likewise increased significantly. A further increase was observed when the
      load was applied to the shoulders. The present findings indicate that metabolic
      power in whole-body VbX can be parametrically controlled by frequency and
      amplitude, and by application of additional loads. These results further
      substantiate the view that VbX enhances muscular metabolic power, and thus muscle
      activity.

PMID- 12215963
TI  - Time to exhaustion at VO(2)max is related to the lactate exchange and removal
      abilities.
AB  - The aim of the present study was to investigate the relationships between lactate
      exchange and removal abilities and the capacity to prolong exercise, as assessed
      by the time to exhaustion (Tlim) at a work rate corresponding to VO(2)max (Pa max
      ). The individual blood lactate recovery curves obtained for 13 untrained
      subjects after 5 min 90 % Pa max exercise were fitted to the biexponential time
      function: La(t) = La(0) + A(1) (1-e (-gamma(1) x t) + A(2) (1-e (-gamma(2) x t),
      where t is time into the recovery, La(0) is the arterialized lactate
      concentration measured at the end of the exercise, gamma(1) and gamma(2) are
      velocity constants denoting the lactate exchange and removal abilities,
      respectively. Tlim was positively related to gamma(1) and gamma(2) (r = 0.60, p <
      0.05 and r = 0.56, p < 0.05, respectively) but was negatively related to La(0) (r
      = 0.75, p < 0.01). gamma()1 was positively related to the capillary density (r =
      0.69, p < 0.01) and to the number of capillaries per type I fiber area (r = 0.62,
      p < 0.05). It was concluded that 1) high lactate exchange and removal abilities
      would allow continuing a high-intensity exercise for a longer duration, and 2) a
      high capillary density may explain the associated high lactate exchange ability.

PMID- 12215964
TI  - Effects of high intensity intermittent training on peak VO(2) in prepubertal
      children.
AB  - This study was designed to examine peak VO(2) responses of prepubescent children
      following a 7-week aerobic training. Twenty-three boys and thirty girls (9.7 +/-
      0.8 years) were divided into a high intensity experimental group (HIEG: 20 girls
      and 13 boys) and a control group (CG: 10 girls and 10 boys). A graded 20-m
      shuttle run with measurement of gas exchange values was performed prior to and
      after the 7-week training program. The test consisted of a 3-min run at 7 km x h(
      1) to determine energy cost of running, immediately followed by a 20-meter
      shuttle run test. HIEG had two 30 min-sessions of short intermittent aerobic
      training per week at velocities ranging from 100 up to 130 % of the maximal
      aerobic speed. For HIEG, absolute peak VO(2)(9.1 %) and relative to body mass
      peak VO(2)(8.2 %) increased significantly (p < 0.001); it was unchanged in the
      CG. Similarly, maximal shuttle run improved significantly in HIEG (5.1 %, p <
      0.001). In contrast, there was no significant change for CG. For both groups
      energy cost of running remained unchanged. These findings show that prepubescent
      children could significantly increase their peak VO(2) and maximal shuttle
      velocity with high intensity short intermittent aerobic exercises.

PMID- 12215965
TI  - Effects of RRR-alpha-tocopherol on leukocyte expression of HSP72 in response to
      exhaustive treadmill exercise.
AB  - Previous research revealed an increased expression of HSP72 in leukocytes after
      vigorous endurance exercise. We questioned whether more intensive but shorter
      exercise also induces leukocyte HSP72 synthesis. To delineate the role of
      reactive oxygen species (ROS) in exercise-related HSP72 induction, we
      additionally examined the effect of RRR-alpha-tocopherol (alpha-toc) on HSP72
      expression using a double-blind placebo (P) controlled cross-over design. After
      supplementation with alpha-toc (500 I.U. daily) or P for 8 days, 9 male subjects
      performed a combined exhaustive treadmill protocol (total duration 29.4 +/- 2.0
      min). HSP72 was assessed on mRNA (RT-PCR) and protein levels (flow cytometry).
      HSP72 mRNA rose 3 h after exercise only in the P group, but individual
      differences (alpha-toc - P) did not reveal significant treatment effects. A
      moderate but significant rise of HSP72 protein occurred in granulocytes up to 48
      h after exercise. Three hours post-exercise, granulocyte HSP72 protein was lower
      when subjects received alpha-toc, but this effect vanished 24 and 48 h post
      exercise. Exhaustive treadmill exercise augments HSP72 mRNA in leukocytes and
      induced a moderate but prolonged response of granulocyte HSP72 protein. These
      exercise effects are lower when compared to earlier findings obtained after
      vigorous endurance exercise. ROS seem to be involved, but do not play the major
      role in the induction of granulocyte HSP72 synthesis after exhaustive exercise.

PMID- 12215966
TI  - s-IgA response in females following a single bout of moderate intensity exercise
      in cold and thermoneutral environments.
AB  - Previous research has linked exercise under unfavourable environmental conditions
      to decreased concentration and/or secretion rate of secretory immunoglobulin A (s
      IgA). The purpose of this study was to investigate the influence of moderate
      exercise in a thermoneutral (TN) and a cold (COLD) environment on the
      concentration of s-IgA and the secretion rate of s-IgA in moderately active
      females. Sixteen females (23.4 +/- 6.8 yrs, 61.1 +/- 5.9 kg, 1.64 +/- 0.07 m)
      served as subjects for this study. On separate occasions, one week apart, all
      subjects ran or walked for 30 minutes at 71 % of individual heart rate reserve on
      an outdoor (1 degrees C) or an indoor track (24 degrees C). Unstimulated saliva
      samples were collected for 4-min immediately pre (PR), post (POST), and 30-min
      post (30POST) exercise. Profile of Mood State (POMS) questionnaires were
      completed pre and post exercise intervention and Global Mood State (GMS) was
      calculated. The absolute concentration of s-IgA, and total non-specific protein
      were measured and the secretion rate of s-IgA and s-IgA:Protein were calculated.
      Analysis of Variance (ANOVA) revealed that flow rate increased in COLD and
      decreased in TN such that it was significantly lower (POST) and (30POST) in the
      TN environment when compared to COLD. There was a significant increase in the
      secretion rate of s-IgA at 30POST for the COLD trial and a significant decrease
      at 30POST for the TN trial. No significant differences were found for the
      concentration of s-IgA, the s-IgA:Protein:ratio, or GMS. Stepwise regression
      revealed that with all predictors in the model, only the concentration of s-IgA
      accounted for a significant proportion of the variance in cold temperature, while
      in the TN environment, both the concentration of s-IgA and the flow rate
      accounted for significant proportions of the variance. These findings suggest
      that moderate exercise in cold temperatures does not decrease secretion rate of s
      IgA, while exercise in TN temperatures does.

PMID- 12215967
TI  - Elbow load with various forearm positions during one-handed pushup exercise.
AB  - This is the first study of the one-handed pushup, and tries to show the effects
      of forearm rotations. Previous studies of elbow loading have focused on passive
      loading and small loads, because data from large loads during active exercise is
      not easy to obtain. In order to investigate the biomechanical impact of hand
      position on the elbow and the potential trauma mechanisms of outstretched elbow,
      joint loading across the elbow was analyzed for three forearm rotational
      positions, neutral, 90 degrees internal rotation and 90 degrees external
      rotation. Both kinematic and kinetic data were collected from eight volunteers by
      the Motion Analysis System and a Kistler Force Plate. Statistical analysis of the
      data delineates the relationship between elbow joint load and hand rotational
      position during one-handed pushup, and also provides useful biomechanical
      information for this challenging exercise. The axial and valgus stresses and
      forces are the major concerns. The peak axial forces exerted on the elbow joint
      averaged 65 % of the body weight when the hand position was neutral, and was
      significantly reduced with the hand rotated either internally or externally. The
      peak valgus shear force with the hand externally rotated was 50 % greater than
      the other two positions. Thus, outward rotation of the hand is a stressful
      position that should be avoided during one-handed pushup exercise or forward
      falls with outstretched hands in order to reduce the risk of elbow injuries.

PMID- 12215970
TI  - Detection and characterization of renal masses and staging of renal cancers: new
      considerations in the era of helical computed tomography.
AB  - With the introduction of helical CT and its ability to acquire images very
      rapidly, new problems are being encountered, which can profoundly affect the
      quality of CT examinations performed for evaluation of known or suspected renal
      masses. In this article, these problems are summarized and recommendations made
      for CT techniques that will maximize sensitivity and specificity in renal mass
      detection, accuracy in renal mass characterization, and accuracy in staging of
      renal cancer.

PMID- 12215968
TI  - GRACILE syndrome, a lethal metabolic disorder with iron overload, is caused by a
      point mutation in BCS1L.
AB  - GRACILE (growth retardation, aminoaciduria, cholestasis, iron overload,
      lactacidosis, and early death) syndrome is a recessively inherited lethal disease
      characterized by fetal growth retardation, lactic acidosis, aminoaciduria,
      cholestasis, and abnormalities in iron metabolism. We previously localized the
      causative gene to a 1.5-cM region on chromosome 2q33-37. In the present study, we
      report the molecular defect causing this metabolic disorder, by identifying a
      homozygous missense mutation that results in an S78G amino acid change in the
      BCS1L gene in Finnish patients with GRACILE syndrome, as well as five different
      mutations in three British infants. BCS1L, a mitochondrial inner-membrane
      protein, is a chaperone necessary for the assembly of mitochondrial respiratory
      chain complex III. Pulse-chase experiments performed in COS-1 cells indicated
      that the S78G amino acid change results in instability of the polypeptide, and
      yeast complementation studies revealed a functional defect in the mutated BCS1L
      protein. Four different mutations in the BCS1L gene have been reported elsewhere,
      in Turkish patients with a distinctly different phenotype. Interestingly, the
      British and Turkish patients had complex III deficiency, whereas in the Finnish
      patients with GRACILE syndrome complex III activity was within the normal range,
      implying that BCS1L has another cellular function that is uncharacterized but
      essential and is putatively involved in iron metabolism.

PMID- 12215971
TI  - Imaging of the urinary tract using multidetector computed tomography urography.
AB  - In the past few years, radiologists have begun to design a single imaging test to
      thoroughly evaluate the urinary tract. Multidetector computed tomography
      urography (MDCTU) is a novel imaging technique that provides high-resolution
      images of the entire renal collecting system in a single helical run. This
      technique lends itself to creating detailed 3-dimensional urograms. Combining the
      known strengths of CT axial data and the 3-dimensional urograms can provide a
      comprehensive evaluation of the genitourinary tract.

PMID- 12215972
TI  - Imaging for nephron-sparing surgery.
AB  - Nephron-sparing surgery is more technically demanding than conventional
      nephrectomy. The urologist can benefit from modern radiological methods to plan
      and monitor surgery and to provide post-surgical surveillance. This article
      describes how 3D volume renderings of CT and MRI data can be useful in planning
      nephron-sparing surgery, how intraoperative imaging can guide surgery and tumor
      ablation, and how CT and MRI can be used to monitor for recurrent disease and
      postoperative complications.

PMID- 12215973
TI  - Magnetic resonance imaging of prostate cancer.
AB  - Management of carcinoma of the prostate has traditionally been guided by digital
      rectal examination, and by laboratory data such as serum prostate-specific
      antigen (PSA) level and histopathologic tumor grade. The introduction of the
      endorectal coil has improved the ability of magnetic resonance imaging (MRI) to
      contribute to staging and treatment planning of prostate cancer, especially in
      cases of confined or locally invasive disease. Exciting research in the fields of
      magnetic resonance spectroscopy (MRS) and MR-guided intervention of the prostate
      may soon expand the role of MRI in the diagnosis and treatment of prostate
      cancer. This article reviews current MRI techniques, the MRI features of prostate
      cancer, the role and efficacy of MRI in prostate carcinoma staging, and the
      current and future uses of MR spectroscopy and MR-guided prostate brachytherapy.

PMID- 12215974
TI  - The utility of monoclonal antibodies in the imaging of prostate cancer.
AB  - Monoclonal antibodies (mAbs) to prostate-specific antigens, such as PSMA, have
      great potential as diagnostic and therapeutic tools in the management of advanced
      prostate cancer. PSMA is a very attractive target for mAb-based imaging. It is
      expressed by virtually all prostate cancers and its expression is further
      increased in poorly differentiated, metastatic, and hormone-refractory
      carcinomas. The ProstaScint scan (Cytogen, Princeton, NJ), based on the mAb 7E11
      C5.3, is currently approved for the imaging of prostate cancer in soft tissue but
      is not approved for imaging bone metastases. It appears superior to conventional
      imaging studies for soft-tissue disease but has limitations attributed to its
      intracellular binding site on PSMA. Overcoming this limitation, new mAbs to the
      extracellular domain of PSMA have been developed. The radioisotopes, (111)Indium,
      (90)Yttrium, and (177)Lutetium have been conjugated to one such mAb, J591.
      Radioimmunoscintigraphy with this immunoconjugate has demonstrated excellent
      tumor targeting of prostate cancer sites not only in soft tissue but also in
      bone.

PMID- 12215975
TI  - The presurgical workup: How much is enough?

PMID- 12215976
TI  - A comparison of conventional panoramic radiographs with volumetric computed
      tomography images in the preoperative assessment of impacted mandibular third
      molars.
AB  - PURPOSE: In the present study, we evaluated the geometric, topographic, and
      anatomic reliability of volumetric computed tomography (VCT) images by comparing
      conventional panoramic radiographs with reconstructed VCT panoramic and paraxial
      images before performing third molar surgery. PATIENTS AND METHODS: A total of 6
      anatomic sites on 10 patients who showed a topographic relationship between the
      apices of the third molar root and the mandibular canal were preoperatively
      assessed by 5 oral surgeons using conventional panoramic radiographs; these were
      complemented and compared with secondary reconstructed paraxial and panoramic VCT
      images. RESULTS: The position of the apices in relation to the mandibular canal
      could be revealed on 94% of VCT reconstructed paraxial images. Assessment of VCT
      paraxial images could be facilitated by using a toolbar marker in 70% of the
      paraxial images. In 90% of the paraxial images, it was possible to assess the
      relationship of the mandibular canal and its adjacent anatomy. The visual grading
      scores for conventional panoramic images were significantly better on all 7
      assessed anatomic sites compared with the reconstructed VCT panoramic images.
      CONCLUSION: The results showed that the VCT paraxial images gave a significantly
      clearer perception of the mandibular nerve than conventional panoramic
      radiographs. However, conventional panoramic radiographs were shown to be better
      than the VCT reconstructed panoramic images and were therefore an invaluable tool
      in the "expert-derived" assessment and posed the potential for identifying the
      need for further VCT diagnostic procedures.

PMID- 12215977
TI  - Auricular cartilage graft interposition after temporomandibular joint ankylosis
      surgery in children.
AB  - PURPOSE: After surgery for temporomandibular joint (TMJ) ankylosis, relapse is
      frequently due to fibrosis and ossification occurring in the space of the joint.
      The object of this study was to evaluate the use of autogenous auricular
      cartilage graft as an interposition material after arthroplasty of the TMJ
      ankylosis. PATIENTS AND METHODS: Seven patients with TMJ ankylosis were treated
      with autologous auricular cartilage graft interposition arthroplasty. With 4 to 6
      years of follow-up, the function of the TMJ was evaluated. RESULTS: In 7 patients
      with TMJ ankylosis treated with autologous auricular cartilage graft
      interposition arthroplasty, the function of the TMJ recovered well. At 6-year
      follow-up, no relapse had occurred and no deformities resulted in the ear from
      which the cartilage had been harvested. CONCLUSION: Autologous auricular
      cartilage interposition arthroplasty is an ideal method for the prevention of
      relapse of TMJ ankylosis.

PMID- 12215978
TI  - Effect of maxillomandibular fixation on the incidence of postoperative pulmonary
      atelectasis.
AB  - PURPOSE: Our goal was to assess the role of maxillomandibular fixation (MMF) on
      postoperative atelectasis. PATIENTS AND METHODS: We examined 64 patients in 2
      groups: MMF and non-MMF. Atelectasis was diagnosed by comparing preoperative and
      postoperative chest radiographs, arterial blood gas analysis, and axial
      temperatures. Postoperative chest computed tomography scans were also used as the
      best way to detect atelectasis. RESULTS: Of the MMF and non-MMF patients, 37.5%
      and 15.6%, respectively, sustained atelectasis (P <.05). Plate type was the most
      prevalent (71%). The right lung was more involved (59%). Fever was not a
      significant finding in atelectatic patients (P >.10). PaO(2) was decreased in
      some cases of atelectasis, especially in patients with extensive involvement.
      CONCLUSION: MMF should be considered as a contributing factor for postoperative
      pulmonary atelectasis.

PMID- 12215980
TI  - The location of parotid gland tumors in relation to the facial nerve on magnetic
      resonance images and computed tomography scans.
AB  - PURPOSE: The facial nerve, which cannot be visualized radiographically in its
      intraparotid part, divides the parotid gland into 2 lobes. When planning surgery,
      it is important to know where to locate a parotid gland tumor in relation to the
      facial nerve, because the location can influence the duration and difficulty of
      the operation. In this study, an anatomic line that predicts the course of the
      facial nerve in the parotid gland, is applied clinically and compared with
      another line recently described to evaluate the usefulness of both tools in the
      use of computed tomography scans and magnetic resonance images. MATERIALS AND
      METHODS: We reviewed 28 scans (15 computed tomography and 13 magnetic resonance)
      and used both lines to predict tumor location in the parotid gland. The accuracy
      of each prediction was checked later by referring to the surgical report.
      RESULTS: This new anatomic line helped us to correctly predict tumor location in
      relation to the facial nerve in 24 cases (85.7%), whereas the other line was
      helpful in 20 cases (71.4%). CONCLUSION: Our new line may be a very useful tool
      to predict the location of parotid gland tumors.

PMID- 12215982
TI  - Treatment of painful temporomandibular joint dysfunction with the sagittal split
      ramus osteotomy.
AB  - PURPOSE: We describe a new indication for the sagittal split ramus osteotomy with
      rigid fixation to treat patients with painful dysfunction of the
      temporomandibular joint. PATIENTS AND METHODS: Ten patients for whom nonsurgical
      management failed were found to have a mandibular condyle positioned postero
      superior within the glenoid fossa with reduced joint space on corrected-axis
      tomograms. The sagittal split ramus osteotomy was used to reposition the proximal
      segment and to increase joint space. Preoperative and long-term postoperative
      (average, 44.7 months) symptoms and tomographic findings were retrospectively
      compared. RESULTS: Significant pain relief occurred postoperatively in all
      patients. One patient had a relapse after initial improvement. No patient
      developed a malocclusion. The long-term radiographic condyle-fossa relationship
      tended to return to its preoperative position with no relapse of clinical
      symptoms, except in the 1 patient. CONCLUSION: The sagittal split ramus osteotomy
      with rigid fixation is another procedure that can be used to treat painful
      temporomandibular joint dysfunction by changing the position of the mandibular
      condyle in the glenoid fossa.

PMID- 12215984
TI  - Ropivacaine for dental anesthesia: a dose-finding study.
AB  - PURPOSE: The purpose of this study was to determine the optimal concentration and
      volumes of ropivacaine for dental anesthesia as regards onset and duration of
      action. SUBJECTS AND METHODS: Thirty healthy individuals with a mean age of 32
      years participated in the study on a voluntary basis. All subjects received a
      ropivacaine injection in 1 of 3 randomized concentrations (2.0, 5.0, or 7.5
      mg/mL) for infiltration anesthesia and mandibular nerve block in a double-blind
      manner. The onset time and duration of anesthesia were assessed by electric pulp
      test, pinprick test of the gingiva, and presence of feeling of numbness of the
      lip. RESULTS: Regardless of dose, only 5 patients received pulpal anesthesia
      after infiltration, but all 3 concentrations anesthetized the gingiva and upper
      lip. The onset of pulpal anesthesia occurred less than 5 minutes after injection
      and lasted for 4 to 58 minutes. Pinprick anesthesia lasted for 8 to 48 minutes,
      and numbness of the upper lip lasted 1 to 4 hours. The effectiveness of the
      mandibular nerve block with regard to pulpal anesthesia was dose dependent. Only
      ropivacaine at 7.5 mg/mL produced sufficient anesthesia. The onset of pulpal
      anesthesia occurred less than 10 minutes after injection and lasted for 2 to 6
      hours. Pinprick anesthesia lasted for 3 to 6 hours and numbness of the lower lip
      lasted for 5 to 9 hours. CONCLUSION: This study shows that ropivacaine could be
      useful as a local anesthetic for mandibular nerve block in dentistry and that the
      very long duration of both pulpal and soft tissue anesthesia may be favorable in
      reducing postoperative pain.

PMID- 12215986
TI  - Effects of age, amount of advancement, and genioplasty on neurosensory
      disturbance after a bilateral sagittal split osteotomy.
AB  - PURPOSE: There are numerous risks for developing neurosensory deficits after a
      bilateral sagittal split osteotomy (BSSO). The purpose of this study was to
      evaluate the effects of genioplasty, length of advancement, and age and their
      interactions in a group of patients undergoing BSSO advancement and followed up
      for 2 years. MATERIALS AND METHODS: Patients were examined at multiple time
      intervals during the 2 years. Measuring in the mental nerve distribution assessed
      damage. 127 subjects were divided into the following 3 age groups: younger than
      24 years, 24 to 35 years, and older than 35 years old. They also were divided
      into small (< or =7 mm) and large (>7 mm) advancements and genioplasty and no
      genioplasty. Change in tactile sensitivity from presurgical to the subsequent
      time periods is reported as a function of these variable and interactions among
      the variables. Data were analyzed using the Kruskal-Wallis test and the Friedman
      test, all at an alpha level of 0.05. RESULTS: Older subjects had greater sensory
      losses than younger subjects. Patients with a genioplasty had a greater loss of
      sensation initially. For all subjects, the sensory function of those receiving
      large and small advancements was not significantly different. Among subjects
      receiving small advancements there was no significant difference among the 3 age
      groups. However, among patients receiving advancements greater than 7 mm, older
      patients did worse. Among patients not receiving genioplasty, there was no
      significant difference among the 3 age groups. In contrast, older subjects with a
      genioplasty had significantly greater sensory deficits. CONCLUSIONS: Age at the
      time of surgery and addition of a genioplasty increases the risk of a
      neurosensory injury. Large advancements further increase the risk of injury in
      older patients.

PMID- 12215987
TI  - A comparative study of osseointegration of Avana implants in a demineralized
      freeze-dried bone alone or with platelet-rich plasma.
AB  - PURPOSE: The purpose of this study was to assess the efficacy of demineralized
      bone powder (DBP) alone or combined in a mixture with platelet-rich plasma (PRP)
      used to enhance osseointegration of dental implants in a dog model. MATERIALS AND
      METHODS: Tissue integration was assessed using standard histomorphometric methods
      at 6 and 12 weeks after surgery. A total of 30 Avana dental implants (SooMin
      Synthesis Dental Materials Co, Busan, Korea) were inserted in the animals. They
      were self-tapping screw implants, 10 mm in length and 4 mm in diameter, made of
      commercially pure titanium. A titanium implant was then placed centrally in each
      defect. In each dog, the defects were treated with 1 of the following 3 treatment
      modalities:1) no treatment (control), 2) grafting with DBP, or 3) grafting with
      DBP and PRP. RESULTS: Histologic analysis showed that all of the bone defects
      surrounding the implants that were treated with DBP, with and without PRP, were
      filled with new bone. The defects that were not treated (control) showed new bone
      formation only in the inferior threaded portion of the implants.
      Histomorphometric results revealed a higher percentage of bone contact with DBP
      and PRP compared with control and DBP. CONCLUSION: These results suggested that
      bone defects around titanium implants can be treated successfully with DBP and
      that PRP may improve bone formation.

PMID- 12215988
TI  - Chondrocyte apoptosis in temporomandibular joints with disc displacement.
AB  - PURPOSE: We sought to study the presence of apoptosis in cartilage from rabbit
      temporomandibular joints with disc displacement (DD), and to examine the
      relationship between chondrocyte apoptosis and chondrocyte proliferation.
      MATERIALS AND METHODS: Thirty Japanese white rabbits were used in this study. The
      right joints of 20 rabbits were subjected to surgical DD. Specimens were
      collected for study at 4 days and 1, 2, 4, and 6 weeks after surgery.
      Temporomandibular joints were studied by microscopy and in situ detection of
      apoptosis. RESULTS: Experimental and sham surgery animals tolerated the surgical
      procedures well, and 16 of 20 of the surgically displaced discs were successful.
      A decrease in the number of chondrocytes in articular cartilage was observed
      after 2 weeks. Apoptotic chondrocytes were abundant in cartilage from DD joints.
      Apoptotic chondrocytes, most obvious at 1 or 2 weeks after surgery, were mostly
      found in the proliferative and hypertrophic zones. At 6 weeks after surgery,
      there were fewer apoptotic chondrocytes, but the cartilage layer was thinner than
      that of the control. CONCLUSION: This study shows that chondrocyte apoptosis is
      increased in rabbit DD articular cartilage at early stage and that the apoptotic
      cells were localized predominantly in the proliferative and hypertrophic zones.
      Chondrocyte death may be of pathogenetic significance during cartilage repair in
      response to DD.

PMID- 12215990
TI  - Characterization of tissue components in the temporomandibular joint disc and
      posterior disc attachment region: internal derangement and control autopsy
      specimens compared by morphometry.
AB  - PURPOSE: Our aim was to morphologically investigate the occurrence of
      fibroblasts, chondrocytes, and blood vessels in the tissue of the
      temporomandibular joint (TMJ) disc, the intermediate zone, and the posterior disc
      attachment region in control autopsy specimens and to compare the results with
      those observed in corresponding tissues from patients with TMJ internal
      derangement. PATIENTS AND METHODS: First, 20 bilateral TMJ disc specimens from
      selected autopsy cases were analyzed by conventional morphometry. Thus, the
      volume density of fibroblasts, chondrocytes, and blood vessels was determined.
      Second, the obtained results from the right joint of the autopsy disc specimens
      were compared with 12 TMJ disc specimens obtained at surgery from patients with
      internal derangement. RESULTS: The tissue compartments of interest (disc,
      intermediate zone, and posterior disc attachment region) were identified
      unequivocally in all specimens. None of the autopsy cases showed any significant
      difference between the right and left joints or related to gender. The only
      variable that differed between autopsy and patient specimens was volume density
      of blood vessels, which was higher in patient specimens. CONCLUSIONS: We found
      that the volume density of blood vessels was significantly higher in the
      posterior disc attachment region in patient specimens than in autopsy controls.
      Whether this reflects a role for vessels in the pathogenesis of TMJ internal
      derangement or merely is a reaction to another type of injury remains to be
      settled. In both the autopsy control and patient specimens, chondrocytes and
      fibroblasts were characteristic for disc respective posterior disc attachment
      region. Thus it appears that the occurrence of these cells can be used to
      distinguish TMJ disc from posterior disc attachment in small biopsy specimens.

PMID- 12215991
TI  - Use of ultrasound to assess healing of a mandibular distraction wound.
AB  - PURPOSE: A standardized, noninvasive technique to assess healing of the
      mandibular distraction wound is not available. Current methods include clinical
      examination, plain radiography, and computed tomography. These imaging techniques
      are expensive and obligate the patient to serial radiation exposure. In addition,
      anatomic overlap and metal artifacts may obscure the distraction gap. In
      contrast, ultrasound has been shown to be a noninvasive, efficient, and
      inexpensive way to evaluate bone healing. The purpose of this study was to test
      the feasibility of ultrasound to evaluate an experimental mandibular distraction
      osteogenesis wound. MATERIALS AND METHODS: Distraction devices were placed via a
      submandibular incision into 24 minipigs. The protocol consisted of 0-day latency
      and distraction rates of 1, 2, or 4 mm/d for a 12-mm gap. The wounds were
      assessed in vivo after 0, 8, 16, and 24 days of neutral fixation. Ex vivo
      radiographs were used to estimate bone fill using a semiquantitative score. A
      semiquantitative ultrasound score was assigned, and the beam penetration depth
      was measured in millimeters. RESULTS: In all groups, clinical stability of the
      distraction wound increased with the duration of fixation. Plain radiographs,
      taken during neutral fixation, showed that the desired distraction gap was
      achieved and maintained. The ultrasound score increased with fixation time,
      whereas beam penetration depth decreased as expected. Ex vivo radiographs showed
      increasing bone fill score with time and paralleled the ultrasound score.
      CONCLUSIONS: The results of this feasibility study indicate that ultrasound is
      potentially useful for the assessment of bone formation in distraction
      osteogenesis wounds.

PMID- 12215992
TI  - Multilocular lesion in the body of the mandible.

PMID- 12215993
TI  - Cerebrospinal fluid: implications in oral and maxillofacial surgery.

PMID- 12215994
TI  - Metastatic lung cancer of the neck: report of 2 cases.

PMID- 12215995
TI  - An unusual supplemental vehicle restraint-induced injury: report of case and
      review of literature.

PMID- 12215996
TI  - Carcinosarcoma (malignant mixed tumor) of the submandibular gland: A case report
      and review of the literature.

PMID- 12215997
TI  - Neurilemmoma of the hard palate.

PMID- 12215998
TI  - Myositis ossificans traumatica of masticatory musculature: A case report and
      literature review.

PMID- 12215999
TI  - Reconstruction of a combined lip-mandible defect by a single fibula flap.

PMID- 12216000
TI  - Alloplastic reconstruction of a temporal bone and glenoid fossa defect.

PMID- 12216001
TI  - Myositis ossificans traumatica of the masticatory muscles: review of the
      literature and report of a case.

PMID- 12216002
TI  - A simple technique to avoid the mandibular nerve in intraoral vertical ramus
      osteotomy.

PMID- 12216003
TI  - Intermaxillary fixation using thermoforming plate.

PMID- 12216004
TI  - The diminishing number of women in surgery.

PMID- 12216005
TI  - Muscle grafts and alternatives for nerve repair.

PMID- 12216007
TI  - Melancholia and axis II comorbidity.
AB  - This study assessed whether the rates of comorbid personality disorders differed
      between DSM-IV melancholic and nonmelancholic major depressive disorder. We
      evaluated 260 consecutive depressed outpatients (140 women [53.8%]; mean age,
      39.01 +/- 10.4 years) with DSM-III-R major depressive disorder (MDD). MDD was
      diagnosed with the use of the Structured Clinical Interview for DSM-III-R-Patient
      Edition (SCID-P); enrolled patients were required to have a score >/= 16 on the
      17-item Hamilton Rating Scale for Depression (HAM-D-17). The presence of the
      melancholic subtype of major depression was determined with the use of a DSM-IV
      checklist, while the presence of personality disorders was assessed using the
      Structured Clinical Interview for DSM-III-R-Personality Disorders (SCID-II). Of
      the 102 (39.2%) patients who met criteria for melancholic depression and the 158
      (60.7%) who did not, there were no significant differences in age, gender, or
      rates of personality disorder diagnoses. We observed no significant difference in
      rates of individual personality disorder clusters between melancholic and
      nonmelancholic depressed patients. Our findings of comparable rates of comorbid
      personality disorders between melancholic and nonmelancholic depression are
      consistent with the decision made by the DSM-IV task force to drop the DSM-III-R
      melancholic feature criterion of "no significant personality disturbance before
      first major depressive episode" as they challenge the usefulness of trying to
      establish such absence of premorbid personality features in acutely depressed
      patients.

PMID- 12216008
TI  - Rapid cycling mood disorder: clinical and demographic features.
AB  - Rapid cycling bipolar disorder is defined as four or more illness episodes per
      year. We compared demographic, clinical, and symptomatological features of
      subjects with rapid cycling bipolar disorder (RC) and those with non-rapid
      cycling bipolar disorder (NR). Five hundred ninety-five subjects (RC = 275, NR =
      320), were included in the study. Subjects were assessed using the Operational
      Criteria for Psychotic Illness checklist (OPCRIT, n = 496), the Hamilton Rating
      Scale for Depression (HAMD, n = 47), the Social Adjustment Scale (SAS, n = 160),
      and the Self-Esteem Scale (SES, n = 160). RC were older at the time of assessment
      and with more medical illnesses. RC showed a lower risk for psychotic and
      disorganised features, particularly within bipolar I disorder. Finally, bipolar I
      RC showed a lower risk for violent suicide attempt. Our findings suggest that
      rapid cycling bipolar disorder is a condition characterized by less severe
      psychotic and suicidal features, particularly within bipolar I disorder.

PMID- 12216009
TI  - Autobiographical memory specificity and the course of major depressive disorder.
AB  - This study examined the stability of autobiographical memory dysfunction (i.e.,
      difficulties in retrieving specific memories) during the course of major
      depressive disorder, its relation to early adverse experiences, and its influence
      on the course of depressive disorder. Using the Autobiographical Memory Test
      (AMT), specificity of autobiographical memory was assessed in 25 subjects with a
      current depressive disorder at baseline, and at 3 and 7 months follow-up. Also,
      information about self-reported childhood traumatization, and demographic and
      clinical variables was obtained. Autobiographical memory performance was
      relatively stable over time despite clinical improvement in the sample. It was
      not related to depression severity at baseline, while higher levels of childhood
      traumatization were correlated with more specific memory performance to negative
      cue words at baseline, but not during follow-up. Specific autobiographical
      responses to negative cue words predicted a better prognosis, whereas specific
      responses to positive cue words were not related to prognosis. Autobiographical
      memory dysfunction in depression appears to be stable over time, is related to
      short-term prognosis in depression, and may act as a vulnerability factor that
      influences the long-term course of depressive disorders.

PMID- 12216010
TI  - The ability of the stress process model to explain mental health outcomes.
AB  - No theory adequately explicates the relationships between stress, social support,
      and health. The recently developed Stress Process Model incorporates multiple
      levels of support and stress at the individual, family, and community level, with
      a focus on predicting mental health outcomes. The purpose of this study was to
      use an existing database to assess the predictive value of the Stress Process
      Model in explaining mental health outcomes in community-dwelling subjects with
      and without panic attacks. This study is a secondary analysis using data obtained
      in 1990 through 1991 for the Panic Attack Care-Seeking Threshold (PACT) study.
      Subjects who agreed to participate completed an in-depth interview concerning
      demographic features, panic characteristics, chronic medical problems, family
      characteristics, illness attitudes and behaviors, coping strategies, symptom
      perceptions, psychiatric morbidity, health care utilization, and functional
      status. The utility of the Stress Process Model is supported by three lines of
      reasoning. First, most of the relationships predicted by the model were
      documented in this study. Second, the model accounted for significant amounts of
      variance in moderating factors, primary and secondary stressors, and mental
      health outcomes. Finally, two of the three hypotheses were supported by this
      study. The integration of family and neighborhood variables into the stress
      process should be attractive to mental health workers in primary care and
      community settings.

PMID- 12216011
TI  - White matter hyperintensities on magnetic resonance imaging of the brain in
      children with psychiatric disorders.
AB  - The current study sought to determine the prevalence, severity, and location of
      white matter signal hyperintensities (WMH) on brain magnetic resonance imaging
      assessments of children and adolescents with psychiatric disorders. Seventy-one
      percent (N = 934) of children admitted to the McLean Hospital Child and
      Adolescent inpatient treatment unit were evaluated with the Diagnostic Interview
      Schedule for Children (DISC) within 7 days of admission during the period 1988 to
      1993 (total, 1,308 admissions). Four hundred eight of these subjects (43.7%) were
      referred for brain magnetic resonance imaging (MRI) scans and became our study
      subjects (mean age, 12.4 years [SD = 2.7]; male/female, 230/178). Study subjects
      were grouped according to a hierarchical diagnostic system as follows:
      schizophrenia (n = 42), bipolar disorder (n = 56), unipolar depression (n = 94),
      conduct disorder/attention deficit disorder (n = 103), and other neurotic
      disorders (n = 30). Subjects without any level 2 diagnosis on DISC (n = 83)
      constituted the comparison group. Bipolar disorder, unipolar depression, and
      conduct disorder/attention deficit disorder groups were significantly more likely
      to have severe levels of WMH than the comparison group (prevalence rates: 17.9%,
      13.8%, 13.6% v 1.2%). In addition, the bipolar disorder group was significantly
      more likely to have severe levels of WMH than the schizophrenia group (prevalence
      rates: 17.9% v 2.4%). The frontal lobes were the predominant locations of WMH in
      the bipolar disorder and unipolar depression groups (76.9% and 60.0%,
      respectively) and also the most frequent location for the conduct
      disorder/attention deficit disorder group (35.7%). The current study reports an
      increased prevalence and severity of WMH in children with bipolar disorder,
      unipolar depression, and conduct disorder/attention deficit disorder relative to
      the comparison group and in children with bipolar disorder compared to those with
      schizophrenia. The development of brain WMH, especially in the frontal lobes, may
      play a role in the pathophysiology of affective disorders in children and
      adolescents.

PMID- 12216012
TI  - History of childhood attention deficit/hyperactivity disorder symptoms and
      borderline personality disorder: a controlled study.
AB  - To evaluate the association between history of childhood attention
      deficit/hyperactivity disorder (ADHD) symptoms and the diagnosis of borderline
      personality disorder (BPD) in adulthood, the Wender Utah Rating Scale (WURS) was
      administered to 42 consecutively admitted BPD subjects, 94 consecutively admitted
      controls with any cluster B personality disorder (PD) diagnosis other than BPD,
      38 consecutively admitted controls with any cluster A or cluster C PD diagnosis
      but no cluster B PD diagnosis, and 69 consecutively admitted controls with no PD
      diagnosis. A fourth control group was composed by 201 nonclinical volunteers.
      According to Dunn-Bonferroni contrasts, BPD subjects showed a significantly
      higher mean WURS total score compared to all control groups (minimum t = 7.93,
      maximum t = 11.63, all Ps <.001). These contrasts remained significant even
      controlling for potential confounders such as antisocial personality disorder
      (ASPD) diagnosis, gender, inpatient status, and axis I diagnoses. The results of
      this study seem to support the hypothesis of an association between history of
      childhood ADHD symptoms and adult BPD diagnosis.

PMID- 12216013
TI  - Clinical characteristics and associated psychopathology of 22 patients with
      kleptomania.
AB  - The current study was constructed to detail the demographic, phenomenological,
      family history, and treatment response data in a group of patients with
      kleptomania. Twenty-two subjects, drawn from an outpatient population, with
      uncontrollable urges to steal completed both a semistructured interview that
      focused on stealing behavior and the Structured Clinical Interview for DSM-IV
      (SCID). Fourteen women and eight men reported an average age of onset of 16 years
      and an average symptom duration of 21 years. Sixteen patients (73%) reported
      particular triggers for their urges to steal. Seventeen subjects (77.3%)
      qualified for a lifetime axis I diagnosis and 9 (40.9%) qualified for a current
      axis I disorder other than kleptomania. These patients reported severe symptoms,
      with 15 subjects (68%) reporting intense shame or guilt following the thefts. We
      conclude that kleptomania is a distressing and disabling disorder associated with
      high rates of psychiatric comorbidity.

PMID- 12216014
TI  - A comparison of DSM-IV brief psychotic disorder with "positive" schizophrenia and
      healthy controls.
AB  - To determine the psychosocial features, course, and outcome of DSM-IV brief
      psychotic disorder (BPD) in a comparative study, we recruited a cohort of 26
      consecutive inpatients fulfilling DSM-IV criteria of BPD as well as a control
      group with "positive" schizophrenia (PS) and psychiatrically healthy controls
      matched for age and sex. Demographic and clinical features were systematically
      evaluated and follow-up investigations were performed at an average of 2.1 years
      after the index episode or 7.8 years after onset of the disorder using
      standardized instruments. The index group of 26 cases represented 2.5% of 1,036
      patients treated as inpatients for psychotic disorders or major affective episode
      during the 5-year inclusion period. Eighty-one percent of the BPD patients were
      female. Indicators of premorbid functioning slightly favored BPD patients. Age at
      first episode and episode frequency did not differentiate between BPD and PS
      patients. Relapse was frequent in both groups. At follow-up BPD patients had a
      significantly more favorable outcome than patients with PS as evidenced by
      employment, independent living, social role functioning, psychological
      impairment, and global functioning. As a group, in many respects BPD patients
      approached the status of psychiatrically healthy controls. DSM-IV BPD is a
      psychotic disorder of favorable prognosis despite frequent relapse.

PMID- 12216015
TI  - Insomnia as a predictor for symptom worsening following antipsychotic withdrawal
      in schizophrenia.
AB  - Sleep disturbances have been associated with schizophrenia, and are an especially
      prominent feature during the prodrome preceding psychotic relapse. In this study,
      we examined the changes in sleep quality following withdrawal of antipsychotic
      treatment, as well as the predictive value of sleep disturbances on symptom
      exacerbation. One hundred twenty-two patients with schizophrenia,
      schizophreniform disorder, or schizoaffective disorder underwent a 3-week
      medication wash-out prior to neuroimaging studies. Sleep quality was rated using
      items on the Hamilton Rating Scale for Depression (HAM-D), while symptom severity
      was measured using the Scale for the Assessment of Negative Symptoms (SANS) and
      the Scale for the Assessment of Positive Symptoms (SAPS). Sleep quality
      deteriorated progressively following antipsychotic discontinuation. Total
      insomnia score prior to antipsychotic withdrawal had a significant effect on the
      severity of psychotic symptoms at the last weekly assessment, while baseline
      terminal insomnia had a significant effect on disorganized symptoms at the end of
      the medication-free period. These findings were independent of baseline symptom
      severity. Our findings suggest that schizophrenia patients with sleep
      disturbances are at a greater risk for worsening of positive symptoms after
      antipsychotic discontinuation. The implications of these findings in research and
      clinical settings are discussed.

PMID- 12216016
TI  - Dimensional structure of the Frankfurt Complaint Questionnaire.
AB  - The Frankfurt Complaint Questionnaire (FCQ) was designed to evaluate the
      subjective symptoms of schizophrenics. Several validation studies of the FCQ
      using principal components analyses (PCA) have shown one-, two-, or four-factor
      solutions. The present study was conducted using FCQ data on 310 schizophrenics
      who met the ICD-10 criteria for F20 (schizophrenia) disorder. Using several
      guidelines to select the number of factors, the PCA yielded one factor. This
      result suggests a unidimensionality underlying FCQ items. A new scale comprising
      24 items was derived from those items with higher weights in the first factor.

PMID- 12216017
TI  - The association of a HOPA polymorphism with major depression and phobia.
AB  - Thyroid hormone has a prominent role in the development and homeostasis of the
      central nervous system (CNS). Consequently, genes participating in thyroid
      hormone receptor (THR)-mediated signal transduction are prime candidates for
      neuropsychiatric illness susceptibility factors. Previously, we have associated
      exonic polymorphisms in a Xq13 thyroid receptor coactivator named HOPA with a
      modest increase in vulnerability to a broad spectrum of neuropsychiatric illness,
      including depression, psychosis, and hypothyroidism. In order to test and extend
      these findings, we have now examined the relationship between HOPA polymorphisms
      and neuropsychiatric illness in a cohort of Iowa adoptees. Consistent with our
      prior findings, HOPA polymorphisms were associated with an increased risk for
      major depression. There was suggestive evidence that the increased psychiatric
      morbidity in these subjects could represent epistasis, e.g., an interaction
      between the HOPA variant and a genetic diathesis for another psychiatric
      condition such as biologic parent antisocial behavior. Information about biologic
      parent behavior and the adoptive home environment was used to determine
      depressive symptoms attributable to gene-environment interaction. HOPA variant
      subjects continued to show significant differences in depressive symptoms when
      controlling for gene-environment interaction. Finally, because obesity is
      associated with hypothyroidism and HOPA polymorphisms are associated with
      hypothyroidism, we analyzed weight with respect to HOPA allele status. We found
      that that HOPA polymorphisms were associated with increased risk for obesity (P
      <.001). In summary, we conclude that HOPA polymorphisms may be a moderate risk
      factor for increased susceptibility to a broad spectrum of neuropsychiatric
      illness and hypothesize that the type of illness manifested might be related to a
      separate genetic diathesis.

PMID- 12216018
TI  - Charnley low-friction arthroplasty: a worldwide retrospective review at 15 to 20
      years.
AB  - This is a retrospective survivorship analysis review of 5089 Charnley low
      friction arthroplasties performed as a primary procedure at 8 hospitals around
      the world before December 31, 1980. Data collected were simple with a well
      defined endpoint: death or revision. There was no clinical or radiographic
      evaluation. The mean age at operation was 63 years; 57% of hips were in women,
      and 43% were in men. The preoperative diagnosis was primary osteoarthrosis in 74%
      of hips. Kaplan-Meier survivorship analysis using failure as revision of any
      component for any cause showed probability of survival at 20 years of 83% (women,
      86%, and men, 78%). In patients aged 70 to 80 at surgery, probability of survival
      was 92%; in patients aged < or =40, probability of survival was 67%. This study
      showed almost identical durability of the femoral versus acetabular component
      87%.

PMID- 12216019
TI  - Total knee arthroplasty in nonagenarians.
AB  - Between 1976 and 1999, 3714 consecutive primary total knee arthroplasties (TKAs)
      were done at our institution. Of these, 20 (0.54%) TKAs were done in 18 patients
      who were > or =90 years old. The average follow-up period was 62.2 months. There
      was 1 postoperative death among the nonagenarians within 90 days of surgery. All
      patients had complete pain relief and excellent knee scores using the Knee
      Society clinical assessment scale. None had an excellent function score at final
      follow-up examination, however. Only 1 patient experienced any surgical
      complications; the patient had wound dehiscence. Five (26.3%) of the surviving 19
      patients had medical complications. The average length of hospital stay was 10.1
      days. Although TKA produced only moderate improvement in knee function for the
      nonagenarians, it produced excellent clinical improvement. TKA improved the
      patients' ability to manage the activities of daily living and their quality of
      life.

PMID- 12216020
TI  - Kinematic comparison of posterior cruciate sacrifice versus substitution in a
      mobile bearing total knee arthroplasty.
AB  - Interest in mobile bearing total knee arthroplasty (TKA) has increased
      significantly. The objective of this in vivo study was to analyze 2 different
      mobile bearing TKAs during gait and during a knee bend from 0 degrees to 90
      degrees flexion. Femorotibial contact positions for 10 subjects, implanted by a
      single surgeon, were analyzed using videofluoroscopy. Five subjects were
      implanted with a posterior-stabilized mobile bearing TKA (PS), and 5 subjects
      were implanted with a posterior cruciate-sacrificing mobile bearing TKA (PCS).
      Each subject, while under fluoroscopic surveillance, performed 2 weight-bearing
      activities: i) normal gait and ii) deep-knee bend. This study showed that the
      kinematic patterns for subjects having either a PS or PCS mobile bearing TKA were
      similar during gait but different during a deep-knee bend. Subjects having a PS
      TKA experienced more posterior femoral rollback of the lateral condyle during the
      deep-knee bend. Findings of kinematic similarities in gait and differences in a
      deep-knee bend between these 2 mobile bearing designs are similar to previously
      published findings of fixed bearing posterior cruciate-retaining and PS TKA.

PMID- 12216021
TI  - Average patient walking activity approaches 2 million cycles per year: pedometers
      under-record walking activity.
AB  - A two-dimensional accelerometer worn on the ankle (step activity monitor [SAM];
      Prosthetic Research Study, Seattle, WA) has been proved to be highly accurate for
      assessing walking activity. The walking activity of 33 patients with well
      functioning total hip arthroplasties was measured continuously during daily life,
      simultaneously with a pedometer and a SAM. The SAM recorded an average of 1.9
      million cycles/y. The pedometer under-recorded an average of 34% cycles per day
      compared with the SAM (P=.0007), but the 2 measures were highly correlated
      (r=0.66; P=.001). No difference was seen in the number of gait cycles per day
      between men and women. The previously reported difference in average walking
      activity between men and women is due to greater under-recording of the pedometer
      in women, especially those with a body mass index > or =27. The pedometer is more
      reliable in quantifying the walking activity of men, less obese women, and
      patients with >1 million gait cycles/y.

PMID- 12216022
TI  - Bone cutting errors in total knee arthroplasty.
AB  - Although achieving precise implant alignment is crucial for producing good
      outcomes in total knee arthroplasty, the contribution of the bone-cutting process
      to overall variability has not been measured previously. Eight orthopaedic
      surgeons with varying amounts of total knee arthroplasty experience performed 85
      resections on 19 cadaver femora and tibiae, and the planes of the resulting cut
      surfaces were compared with the guide planes. Varus-valgus alignment variability
      ranged from 0.4 degrees to 0.8 degrees SD for expert and trainee surgeons.
      Sagittal variability was approximately 1.3 degrees SD for both surgeon groups.
      Slotted cutting guides reduced the variability and eliminated the bias in the
      sagittal plane for experienced surgeons but did not improve significantly frontal
      plane alignment variability. Guide movement contributed 10% to 40% of the total
      cutting error, depending on cut and guide type.

PMID- 12216023
TI  - Fractures of the greater trochanter induced by osteolysis with the anatomic
      medullary locking prosthesis.
AB  - Pathologic fractures of the greater trochanter associated with trochanteric
      osteolysis are a late complication of total hip arthroplasty that have been
      described only in case reports. In this study of 208 consecutive total hip
      arthroplasties with mean 12.2-year radiographic follow-up, we reviewed the
      incidence, presentation, treatment, and outcome of such fractures. A radiographic
      review revealed 9 hips (4.3%) with trochanteric fractures resulting from
      osteolysis, occurring at a mean follow-up of 129 months. Five were diagnosed at
      the time of their radiographic appearance. Four were treated without operative
      fixation, using crutches and limited weight bearing for 4 to 6 weeks. Seven
      fractures healed in situ without major displacement. One resulted in a nonunion
      of the tip of the greater trochanter, and the radiographic outcome of a recent
      fracture was unknown. We found that the risk of sustaining a fracture was
      independent of the size of the osteolytic lesion; however, the risk increased
      significantly when the lysis eroded the cortical bone of the greater trochanter.
      In our experience with the extensively porous-coated AML stem (DePuy, a Johnson &
      Johnson Company, Warsaw, IN), conservative treatment leads to reasonable
      radiographic and clinical results in cases with limited initial fracture
      displacement.

PMID- 12216024
TI  - Surface roughness of the proximal and distal bearing surface of mobile bearing
      total knee prostheses.
AB  - Proximal and distal articulations surface roughness measurements were done on 8
      mobile bearing knee designs immediately after removal from sterile packaging.
      Roughness parameters Ra and Rp based on ISO 97, representing mean deviation from
      the smooth surface line and mean peak to smooth surface line, were recorded using
      a contact surface profilometer at 10 random sites in the anteroposterior and
      mediolateral direction on the femoral and tibial metal components and the
      proximal and distal surface of the ultra-high molecular weight polyethylene (PE)
      inserts. No differences were found for surface roughness values for the metal
      components. Surface roughness values were greater for the distal PE bearing
      surfaces compared with the proximal PE bearing surfaces for each design tested.
      The roughness values for the PE inserts showed a directional dependence. Complex
      kinematics of mobile bearing knees coupled with this rougher distal interface
      could influence the rate of generation of wear particles and total volume of
      particles produced especially in the early postoperative period.

PMID- 12216025
TI  - Continuous-flow cold therapy after total knee arthroplasty.
AB  - Cryotherapy is widely used as an emergency treatment of sports trauma and
      postoperatively especially after anterior cruciate ligament reconstruction.
      Studies in the literature on the effect of cryotherapy after total knee
      arthroplasty (TKA) have been limited and controversial. In this prospective
      study, 60 primary TKAs were done on 30 patients (all staged bilateral TKAs). For
      every patient, 1 TKA had a continuous-flow cooling device applied over the
      surgical dressing immediately postoperatively. The other TKA in the same patient
      (control TKA) was done 6 weeks later and had no cooling device. The study
      compared the range of motion, the volume of hemovac output and blood loss, visual
      analog pain score, analgesic consumption, and wound healing in the 2 limbs of the
      same patient. This study showed that continuous-flow cold therapy is advantageous
      after TKA because it provides better results in all the areas compared.

PMID- 12216026
TI  - The effects of early rollback in total knee arthroplasty on stair stepping.
AB  - We investigated the effects of early compared with late (ie, in flexion) rollback
      on quadriceps efficiency during stair stepping. We studied 10 patients with the
      IB II (Zimmer, Warsaw, IN) total knee arthroplasty (TKA), designed to enforce
      rollback at 73 degrees of knee flexion; 9 patients with the Maxim PS (Biomet,
      Inc, Warsaw, IN) TKA, designed to enforce rollback between 20 degrees and 30
      degrees of flexion; 8 patients with the TRAC PS (Biomet, Inc, Warsaw, IN) mobile
      bearing TKA, designed to enforce rollback at 8 degrees of flexion; and 21 healthy
      control subjects during stair stepping. We measured the external knee flexion
      moments, which must be largely balanced by quadriceps force acting over the
      quadriceps lever arm, as indicators of quadriceps efficiency. The peak external
      knee flexion moment generated by the IB II patients during stair stepping was
      12.4% and occurred at 65 degrees of knee flexion. This moment was significantly
      less (P=.006) than the peak moment, 17.6%, generated by the healthy controls.
      Knee flexion for the IB II patients did not reach 73 degrees, and rollback was
      not enforced until after the peak moment (ie, maximum demands on the quadriceps)
      had been attained. The peak moments generated by the TRAC PS patients, 14.2%, and
      Maxim patients, 14.8%, were not significantly different from that of the
      controls. These results suggest that early as compared with late rollback returns
      more normal quadriceps efficiency during stair stepping.

PMID- 12216027
TI  - Does Chiari osteotomy compromise subsequent total hip arthroplasty?
AB  - We compared 28 total hip arthroplasties done in dysplastic hips after previous
      Chiari osteotomy (group I) with a well-matched control group of 50 primary
      procedures (group II) done during the same period at an average follow-up of 5
      years (range, 25-199 months). Group I required significantly less acetabular
      augmentation, had significantly shorter operative times, had less intraoperative
      blood loss, and had fewer complications than group II. There was no significant
      difference between the 2 groups in terms of clinical or radiographic outcome.
      Total hip arthroplasty after a successful Chiari osteotomy leads to medium-term
      results similar to those of other dysplastic hips. In our experience, less bone
      grafting was required, better coverage of the cup by host-bone was obtained, and
      the center of motion of the hip was more anatomic. Chiari osteotomy may delay the
      need for total hip arthroplasty, may facilitate acetabular reconstruction, and
      does not seem to compromise the medium-term clinical or radiographic outcome.

PMID- 12216028
TI  - Trochanteric fixation in total hip arthroplasty using the S-ROM bolt and washer.
AB  - We evaluated the S-ROM bolt and washer (DePuy, Inc, Warsaw, IN) for fixation of
      the greater trochanter after trochanteric osteotomy in 29 hips in 28 consecutive
      patients. Of 29 cases, 9 (31%) resulted in trochanteric nonunion, with bony union
      being achieved in only 38% of cases. There was dislocation and subluxation in 7
      of 29 (24%) cases with 6 of the 7 dislocations associated with trochanteric
      nonunion. Revision was necessary in 4 of 8 hips to obtain fixation of the
      trochanter. The rate of complications in this series suggests that the S-ROM bolt
      and washer is associated with a high rate of nonunion, particularly in the
      multiply-revised hip. Avoidance of trochanteric osteotomy whenever possible would
      be desirable. When an osteotomy is necessary, alternative forms of fixation
      should be considered.

PMID- 12216029
TI  - Relationship between radiographic measurements of reconstructed hip joint
      position and the Trendelenburg sign.
AB  - We evaluated 60 limbs, including 34 primary total hip arthroplasties in 30
      patients (mean age, 56 years) at a minimum of 2 years postoperatively. Femoral
      offset ratio (%FO) was calculated by dividing the femoral offset by the distance
      between the centers of the bilateral femoral heads on radiographs. The tilt angle
      of the pelvis by the Trendelenburg test was measured using the magnetic sensor
      system. In the limbs having a negative Trendelenburg sign after reconstruction,
      the %FO averaged 20.1% (range, 14.7% to 24.7%), and the tilt angle of the pelvis
      averaged +0.8 degrees (range, -1.0 degrees to +5.0 degrees ). The tilt angle of
      the pelvis correlated positively with %FO (P=.0160, r=0.407). The reconstructed
      hip joint position is crucial to improve hip abductor function.

PMID- 12216030
TI  - Interobserver and intraobserver variability in radiographic assessment of
      osteolysis.
AB  - This study quantified the variability associated with diagnosing periprosthetic
      osteolysis from the radiographs of total hip arthroplasty patients. Four joint
      arthroplasty surgeons independently assessed radiographs of 60 patients for
      evidence of osteolysis in different zones. The surgeons agreed on the presence of
      lesions in at most 57% of the zones. kappa coefficients, used to quantify the
      extent of agreement among the surgeons, denoted poor interobserver
      reproducibility (kappa =.28 to.44). Intraobserver reliability-determined by
      comparing 2 reviews of the same radiographs done by 1 surgeon 2 weeks apart-was
      moderate to excellent (kappa =.48 to.84). We also compared the results from the
      most recent radiograph with those from a time series. Agreement improved when a
      series was reviewed. Reliable comparisons cannot be made with osteolysis rates
      reported by different observers. In the research setting, osteolysis rates are
      more reliable if they are determined by a single reviewer whose intraobserver
      variability has been reported. In assessing a patient for osteolysis, it is more
      accurate to analyze a series of radiographs than the most recent radiograph.

PMID- 12216031
TI  - Prediction of total knee arthroplasty polyethylene wear using the wear index.
AB  - The predictive value of the wear index for total knee arthroplasty polyethylene
      wear was determined using a numeric and in vitro model. The wear index was
      defined as the deformation x the sliding velocity. Four commercially available
      total knee prostheses were modeled for this study. Deformation and sliding
      velocity were calculated from the 3-dimensional geometry of the components and
      the gait kinematic inputs using Hertz's formula. A knee simulation test was
      performed under the same conditions, and the surface of the inserts was compared
      with the wear index. This study showed good agreement between the numeric model
      and the simulation test, suggesting that the wear index is a reliable predictor
      of total knee arthroplasty polyethylene wear through its incorporation of contact
      stress and kinematics.

PMID- 12216032
TI  - Is coding of diagnoses, comorbidities, and complications in total knee
      arthroplasty accurate?
AB  - Coding of diagnoses, comorbidities, and complications is important for health
      care delivery, not only for appropriate hospital and physician reimbursement, but
      also for a correct assessment of complication rates. The purpose of this study
      was to determine the agreement of coding of diagnoses, comorbidities, and
      complications for total knee arthroplasty between 2 groups of coders. Between
      January 1, 1997, and November 18, 1997, 100 consecutive primary total knee
      arthroplasties were done by 2 orthopaedic surgeons. Diagnoses, comorbidities, and
      complications were coded by professional hospital coders according to the
      Healthcare Finance Administration guidelines, then recoded by a second team with
      orthopaedic experience. Although the hospital coders matched diagnoses with the
      orthopaedic team 96.5% of the time, they determined a complication rate of 1.4
      per patient and a comorbidity rate of 2.9 per patient, whereas the orthopaedic
      team coded for 0.7 complications per patient and 3.7 comorbidities. Based on
      these results, there should be interaction and communication between hospital
      coders and health care professionals to check that coding is accurate and
      reproducible.

PMID- 12216033
TI  - Morse-type tapers: factors that may influence taper strength during total hip
      arthroplasty.
AB  - We studied the effect of varying impaction force, repeated impactions, and fluid
      contamination on the disassembly strength of Morse-type tapers in 4 commercially
      available, modular femoral total hip components. The effect of varying techniques
      of taper assembly on the distraction force was studied. Our results show a
      reproducible and linear relationship between the taper impaction force and the
      disassembly force. The force necessary to separate the taper for a given
      impaction force varied, however, among manufacturers. Repeated impactions added
      little strength, and we found that when multiple impactions of varying force are
      used, the strength is roughly equivalent to the expected strength from the single
      strongest blow. Fluid contamination at the taper interface had unpredictable
      effects on taper strength.

PMID- 12216034
TI  - Surgical release of iliopsoas tendon for groin pain after total hip arthroplasty.

PMID- 12216035
TI  - A method for improving acetabular preparation during cemented all-polyethylene
      acetabular component insertion during total hip arthroplasty.
AB  - Long-term outcome from cemented acetabular components has been correlated with
      the presence of radiolucency on early postoperative radiographs. We describe a
      means for enhancing acetabular bed preparation to decrease blood at the bone
      cement interface and to obtain better pressurization of the cement into the
      cancellous bone of the acetabulum during cemented acetabular component insertion.

PMID- 12216036
TI  - A simple method for construction of an articulating antibiotic-loaded cement
      spacer.
AB  - A 2-stage exchange protocol has been used widely in North America for management
      of infected total hip arthroplasties. Many surgeons choose to use an antibiotic
      loaded cement spacer in the interval before reimplantation of the final
      prosthesis. We propose a simple technique for the construction of an articulating
      antibiotic-loaded spacer for use as part of 2-stage exchange protocol for the
      treatment of infected total hip arthroplasties.

PMID- 12216037
TI  - Preoperative identification of a bone-cement allergy in a patient undergoing
      total knee arthroplasty.
AB  - Allergy to polymethyl methacrylate bone-cement or its components is unusual.
      Because of the potential for an inflammatory response in an allergic patient and
      the possibility of pain and loosening if a cemented implant is used, it is
      imperative to identify patients with this allergy to modify their treatment. We
      report the case of an otherwise healthy 60-year-old woman who needed a total knee
      arthroplasty and who had an allergy to methyl methacrylate bone-cement identified
      preoperatively. The appropriate evaluation for a patient who is suspected to have
      an allergy to bone-cement or its components is reviewed.

PMID- 12216038
TI  - Dissecting popliteal cyst resulting from a fragmented, dislodged metal part of
      the patellar component after total knee arthroplasty.
AB  - Dissecting popliteal cyst is an uncommon complication after total knee
      arthroplasty, occurring mainly as a result of either rheumatoid arthritis or a
      malfunctioning knee prosthesis. Its association with a failed metal-backed
      patellar component has not been reported since the introduction of the
      resurfacing of the patella with this kind of design in 1980. We present a case of
      a late fracture-dislocation of the metal part of the patellar component that
      migrated to the posterior popliteal fossa, resulting in a cystic mass formation
      caused by a foreign body granuloma. The patient was treated successfully with a 2
      stage operation: first, revision of the total knee arthroplasty and, second,
      excision of the cyst. The patient had a pain-free functional knee 7 years after
      surgery, with no recurrence of the symptoms or the popliteal cyst.

PMID- 12216039
TI  - Polyethylene liner exchange for excessive wear and osteolysis.
AB  - To determine if polyethylene liner exchange of a total hip arthroplasty decreased
      wear and slowed the progression of osteolysis, we evaluated 10 hips at a mean 6.2
      years after component exchange. Head penetration and lesion size were quantified
      on serial radiographs using computer-assisted techniques. A mean 7.9 years before
      component exchange, true polyethylene wear rates averaged 0.36 +/- 0.19 mm/y. A
      mean 6.2 years after component exchange, average wear rates decreased to 0.17 +/-
      0.11 mm/y. Similarly, mean acetabular and mean femoral lesion growth rates
      decreased. At last follow-up, all components remained radiographically stable.
      Complications included dislocation (1 patient) and increased wear (2 patients).
      Modular component exchange with removal of granulomatous tissue has the potential
      to decrease wear and slow the progression of osteolysis without subsequent
      component loosening.

PMID- 12216040
TI  - Normocalcemic primary hyperparathyroidism with fractures.
AB  - Normocalcemic primary hyperparathyroidism is an uncommon condition usually found
      among patients with urinary stones. To the best of our knowledge, this is the
      first case of a patient with normocalcemic primary hyperparathyroidism presenting
      with bilateral femoral neck fracture. A 45-year-old man had pain both hip joints
      and limping in for several months. Vertical fractures of bilateral femoral necks
      were found by radiographs. Laboratory findings showed a normal value of total
      serum calcium but elevated serum ionized calcium. Serum parathyroid hormone and
      alkaline phosphatase levels were elevated. The patient was treated with
      subtrochanteric valgus osteotomy fixed with a dynamic hip screw and total
      parathyroidectomy. Histopathologic examination showed hyperplasia of the
      parathyroid glands. At 1-year follow-up, the patient was doing well clinically.

PMID- 12216041
TI  - Re: Safe screw placement in acetabular revision surgery.

PMID- 12216043
TI  - 2001 Annual report of the American Association of Poison Control Centers Toxic
      Exposure Surveillance System.

PMID- 12216044
TI  - Effect of intra-aortic occlusion balloon in external thoracic compressions during
      CPR in pigs.
AB  - This study was performed to compare the effectiveness of external thoracic
      compressions with and without intra-aortic occlusion balloon with capnography and
      coronary and cerebral perfusion pressure (CPP) in the normothermic and traumatic
      less cardiopulmonary arrest provoked by a ventricular fibrillation in pigs. This
      was an experimental study (cross-over study) in 14 pigs with similar
      characteristics (23 +/- 2 kg, 10-12 weeks of age). After an 8-minute
      nonintervention period, the cardiopulmonary resuscitation (CPR) consists of 4
      periods of 5 minutes alternating CPR with and without intra-aortic occlusion
      balloon. Main outcomes measured are end-tidal CO(2) (ETCO(2)); intra-aortic,
      coronary, and cerebral perfusion pressures; blood gas analysis; and blood lactate
      concentration. At the end of each period, levels are obtained. Postmortem study
      was made. Inflation of the occlusion balloon provokes an expansion in the ETCO(2)
      of about 38%. The coronary perfusion pressure initially goes from 10.21 to 29.0
      mm Hg after the occlusion of the aorta, which means an increase of 150%. The CPP
      goes from 12.54 to 39.71 mm Hg after the balloon was inflated, which means an
      increase of 200%. In all cases the differences are statistically significant (P
      <.0001). These increases are less important in the final periods. Intra-aortic
      balloon occlusion increased ETCO(2), coronary, and cerebral perfusion pressures.
      An early application of this technique was important.

PMID- 12216046
TI  - Tap water for irrigation of lacerations.
AB  - This study was designed to compare the infection rates of simple lacerations
      irrigated with tap water versus sterile normal saline before repair. Patients
      with simple lacerations to an extremity that were less than 8 hours from injury
      were prospectively enrolled. Exclusions from the study were: dog bites, hand
      lacerations, immunocompromised patients, and those on antibiotics at the time of
      injury. Patients who qualified were randomized to receive tap water or normal
      saline for wound irrigation. Before and after irrigation, wound cultures were
      obtained. After the procedure was complete, patients were scheduled for a 48 hour
      follow-up wound check. A total of 46 patients were enrolled in the study. Twenty
      four patients were randomized to the normal saline group and 21 were assigned to
      receive tap water irrigation. There were 2 infected lacerations in both the tap
      water and normal saline groups. The organisms cultured from the wounds in both
      groups were similar and there was no difference in colony counts when tap water
      was used. The use of tap water for the irrigation of lacerations does not result
      in the growth of unusual organisms or increase the colony counts of organisms.
      Wound infection rates were the same in both groups. This pilot study suggests
      that the use of tap water for irrigation of wounds may be safe. Further
      validation is necessary.

PMID- 12216045
TI  - Prospective age-based comparison of behavioral reactions occurring after ketamine
      sedation in the ED.
AB  - The study objective was to prospectively evaluate the frequency and severity of
      behavioral reactions occurring in children receiving ketamine sedation in the
      emergency department (ED). A behavioral observational study was conducted.
      Ketamine was given in a standardized protocol with midazolam, atropine, and a
      prehypnotic suggestion. Descriptions of behavioral reactions were recorded
      immediately after the procedure, and longitudinal follow-up was made in 1 day, 1
      week, and 1 month. A total of 301 patients were enrolled. Mild reactions
      described as not unpleasant occurred in 7/205 (3.4%, 95% CI 0.9-5.9%) of the
      younger age group, and 2/96 (2.1%, 95% CI 0-5.0%) of the older age group.
      Unpleasant reactions occurred in 2/205 (1.0%, 95% CI 0-2.4%) of the younger age
      group, and 4/96 (4.2%, 95% CI 0-8.2%) of the older age group. We observed no
      clinically important difference in the proportion of older versus younger
      children experiencing behavioral reactions after IV ketamine sedation.

PMID- 12216047
TI  - Patients' self-treatment with alternative treatment before presenting to the ED.
AB  - This study examined the frequency of patients using alternative medicine to treat
      their condition before presenting to an emergency department (ED). This was a
      prospective randomized, consecutive survey conducted at a level I 24-bed inner
      city trauma center. Patients were eligible for enrollment if they were at least
      18 years old and able to consent. Exclusion criteria included patients delivered
      by an ambulance and patients unable or unwilling to consent. The questionnaire
      collected information about sociodemographic variables, alternative treatment
      used, why was it used, who prescribed the treatment, route, treatment
      satisfaction, and past history of alternative treatment and medication use. A
      total of 189 patients were surveyed. Of these, 10.6% of the surveyed patients
      used alternative treatment. The most common reason for using alternative medicine
      was "I wanted to try the simplest treatment first" (55%). These treatment options
      were self-prescribed by 55%, advice from a friend or family member by 40% and
      other health professional in 5%. The alternative medicines included massage
      (35%), home remedies (20%), prayer (20%), chiropractor (15%), herbal medicines
      (5%) and other methods (5%). The treatment was administered orally (20%) or
      topically (80%). Most said that the alternative therapy was helpful (60%). The
      use of alternative therapy versus no use of alternative therapy was correlated
      with gender (P =.05), treatment (P =.025) and how it was administered (P =.021).
      A small but significant number of inner-city patients use alternative treatments
      before presenting to an ED. Emergency physicians need to consider the use of
      alternative treatment and medicine by patients presenting to the ED for
      treatment.

PMID- 12216048
TI  - Prevalence and risk factors associated with hepatitis C in ED patients.
AB  - The objective of this study was to measure the prevalence of and identify risk
      factors associated with hepatitis C virus (HCV) in emergency department (ED)
      patients. Adults presenting to an urban university teaching hospital, having
      blood drawn as part of their routine evaluation, had an extra tube drawn and
      tested for HCV. English-speaking adults consenting to participate in the survey
      portion of the study were administered an in-depth risk factor questionnaire. A
      case-control analysis was used to identify risk factors in HCV+ compared with HCV
      subjects. Contingency table analyses using the Fisher exact test, odds ratios
      (OR), and 95% confidence intervals (CI) were used for risk factor identification.
      Of 223 blood samples, 38 (17%) were positive for antibodies for HCV. One hundred
      twenty-one subjects (54%) agreed to the risk factor survey, 18 (15%) of whom were
      HCV+. Of the 18 HCV+ survey participants, 12 new diagnoses of HCV were made. A
      history of injection drug use was the most significant risk factor associated
      with HCV (OR 858.5, CI 61.8-22,026.5). A high prevalence of HCV is found in
      selected urban ED patients. Most of these patients have a constellation of risk
      factors including a history of injection drug use. Efforts to identify at risk
      patients for serologic testing and follow-up should be initiated. Identifying
      undiagnosed HCV can lead to interventions to decrease transmission as well as
      reduce the morbidity and mortality of disease.

PMID- 12216049
TI  - Effect of levalbuterol on prehospital patient parameters.
AB  - This study was performed to determine if levalbuterol improves dyspnea as
      assessed by prehospital clinical parameters. All EMS patients >or=16 years old
      given nebulized levalbuterol over 6 months were included in this prospective,
      open-label work. Data collected included demographics, initial pulse rate (P),
      respiratory rate (R), patient report of respiratory distress (S), and peak
      expiratory flow (PF). Outcome variables were P, R, S, and PF after levalbuterol
      use. Statistical analysis used t tests, with P <or=.05. One hundred forty-seven
      patients were enrolled. Mean age was 65.9 years (62.6% women). Significant
      decreases in P, R, and S, and a significant increase in PF, were noted after
      levalbuterol administration. Levalbuterol produces significant improvement in EMS
      respiratory patient parameters. Tachycardia does not appear to be a side effect
      of levalbuterol administration. The results support the use of levalbuterol in
      prehospital care.

PMID- 12216050
TI  - Orthopedic pitfalls in the ED: slipped capital femoral epiphysis.
AB  - Slipped capital femoral epiphysis (SCFE), though a relatively common disorder, is
      frequently missed on initial presentation. Symptoms can be vague, the physical
      examination unrevealing, and radiographic abnormalities subtle. Prompt diagnosis
      of SCFE is important, however, to improve clinical outcome. The emergency
      physician needs to remain vigilant for this diagnosis to avoid this orthopedic
      pitfall. This article examines the clinical presentation, diagnostic techniques,
      and management options applicable to the emergency physician in the treatment of
      SCFE.

PMID- 12216051
TI  - Acute psychosocial stress and cardiovascular events.
AB  - Stressful life events can trigger acute myocardial infarction and sudden cardiac
      death. Victims of natural disasters, such as earthquakes and other conditions of
      extreme stress should be evaluated for physical injuries as well as for cardiac
      disease.

PMID- 12216052
TI  - Wide-QRS complex tachycardia during pregnancy: treatment with cardioversion and
      review.

PMID- 12216053
TI  - Spontaneous splenic rupture in recurrent acute pancreatitis.

PMID- 12216054
TI  - A new human-dynamic simulator (Air Man) for airway training in emergency
      situations.

PMID- 12216055
TI  - Overview: the epidemiology of neurodevelopmental disorders.

PMID- 12216056
TI  - The epidemiology of mental retardation: challenges and opportunities in the new
      millennium.
AB  - There are a number of problems and challenges in relating the science of
      epidemiology to mental retardation (MR). These relate to how MR is defined and
      classified and how these definitions may change over time. These as well as other
      differences in ascertainment sources and methods need to be considered when
      comparing MR prevalence over time and place. On the other hand, advances in
      technology also provide new and efficient methods of data collection both by data
      linkage and by use of web-based methods to study rare diseases. While prevalence
      studies have not been individually reviewed, we have examined the range of data
      including recent studies relating to how prevalence differs according to age,
      gender, social class and ethnicity. Some problems with available etiological
      classification systems have been identified. Recent etiological studies, most of
      which use different classification systems, have been reviewed and explanations
      have been postulated to account for differences in results. Individual risk
      factors for MR are considered whilst the option of considering a population as
      opposed to a high risk strategy to MR prevention is raised. This might well
      involve improving the social milieu surrounding the occurrence of individual risk
      factors. The impact of biotechnological advances such as antenatal and neonatal
      screening and assisted reproduction on MR are discussed. The issue of how
      inequalities in access to technology may impact on case identification and even
      have the potential to further widen inequalities is raised. The importance of
      extending the use of epidemiological tools to study the social, health and
      economic burden of MR is also emphasized. However, in order to apply to MR the
      "prevention-intervention-research" cycle, which surely underpins all
      epidemiology, it is vital to ensure that the methodological challenges we raise
      are adequately addressed.

PMID- 12216057
TI  - Cerebral palsy in very preterm infants: new epidemiological insights.
AB  - The focus of this review is on new insights from recent epidemiological research
      on cerebral palsy in preterm infants. These include: 1) a better understanding of
      issues related to diagnosis and classification; 2) new information about the
      brain abnormalities underlying cerebral palsy in preterm infants; and 3) a better
      understanding of biological mechanisms that may underlie previously described
      epidemiological associations. Ongoing efforts to improve the diagnosis and
      classification of cerebral palsy have been enhanced by findings from serial
      examinations of cohorts of very preterm infants. Cranial ultrasonography through
      the anterior fontanelle of very preterm infants has provided information about
      grossly evident brain damage, found in about one-half of preterm infants who
      develop cerebral palsy. Insights into the pathophysiologic basis for certain
      epidemiologic associations have come from studies of experimental brain damage in
      animals and clinical studies of neurologic disorders in adults. Much of the
      current epidemiological research into the causes of cerebral palsy in preterm
      infants has focused on two potential mechanisms of brain damage. One mechanism
      involves insufficient cerebral perfusion; the other, cytokine-mediated damage,
      potentially triggered by events such as maternal infection (e.g., intrauterine or
      periodontal infection), neonatal infection (e.g., sepsis and necrotizing
      enterocolitis), and neonatal oxygen- or ventilator-induced lung injury. In
      addition to the preterm infant's increased exposure to such damaging factors, the
      high frequency of cerebral palsy in these infants might be due, in part, to
      insufficient levels of developmentally regulated protective substances, such as
      thyroid hormone and glucocorticoids. Models of causation currently are being
      investigated using recently developed methods for quantifying, with small
      quantities of blood, biomolecules that are suspected to either promote or protect
      against brain damage in the neonate. Clinical investigations now under way can be
      expected to identify strategies to be tested in clinical trials that could lower
      the risk of cerebral palsy in very preterm infants.

PMID- 12216058
TI  - The epidemiology of cerebral palsy in term infants.
AB  - Half of cerebral palsy (CP) arises in infants of normal birthweight; yet, many
      fewer studies seek to identify risk factors for CP in term and near-term infants
      than in those born very prematurely. There has been no net decrease in the
      prevalence of CP in term and near-term infants over recent decades. Potentially
      asphyxiating birth complications account for a small minority of CP cases. Recent
      studies suggest that disorders of coagulation and intrauterine exposure to
      infection or inflammation are associated with risk of CP, and that both can be
      accompanied by signs of neonatal encephalopathy, the best available predictor of
      CP in term neonates. Therapeutic interventions directed at preventing
      interruption of oxygen supply have not been shown to reduce the occurrence of CP.
      There have not yet been studies examining whether medical interventions directed
      at infection or coagulation disorder can reduce the frequency of CP.

PMID- 12216059
TI  - The epidemiology of autistic spectrum disorders: is the prevalence rising?
AB  - For decades after Kanner's original paper on the subject was published in 1943,
      autism was generally considered to be a rare condition with a prevalence of
      around 2-4 per 10,000 children. Then, studies carried out in the late 1990s and
      the present century reported annual rises in incidence of autism in pre-school
      children, based on age of diagnosis, and increases in the age-specific prevalence
      rates in children. Prevalence rates of up to 60 per 10,000 for autism and even
      more for the whole autistic spectrum were reported. Reasons for these increases
      are discussed. They include changes in diagnostic criteria, development of the
      concept of the wide autistic spectrum, different methods used in studies, growing
      awareness and knowledge among parents and professional workers and the
      development of specialist services, as well as the possibility of a true increase
      in numbers. Various environmental causes for a genuine rise in incidence have
      been suggested, including the triple vaccine for measles, mumps and rubella
      (MMR]. Not one of the possible environmental causes, including MMR, has been
      confirmed by independent scientific investigation, whereas there is strong
      evidence that complex genetic factors play a major role in etiology. The evidence
      suggests that the majority, if not all, of the reported rise in incidence and
      prevalence is due to changes in diagnostic criteria and increasing awareness and
      recognition of autistic spectrum disorders. Whether there is also a genuine rise
      in incidence remains an open question.

PMID- 12216060
TI  - The epidemiology of attention-deficit/hyperactivity disorder (ADHD): a public
      health view.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is the most common
      neurodevelopmental disorder of childhood. However, basic information about how
      the prevalence of ADHD varies by race/ethnicity, sex, age, and socio-economic
      status remains poorly described. One reason is that difficulties in the diagnosis
      of ADHD have translated into difficulties developing an adequate case definition
      for epidemiologic studies. Diagnosis depends heavily on parent and teacher
      reports; no laboratory tests reliably predict ADHD. Prevalence estimates of ADHD
      are sensitive to who is asked what, and how information is combined.
      Consequently, recent systematic reviews report ADHD prevalence estimates as wide
      as 2%-18%. The diagnosis of ADHD is complicated by the frequent occurrence of
      comorbid conditions such as learning disability, conduct disorder, and anxiety
      disorder. Symptoms of these conditions may also mimic ADHD. Nevertheless, we
      suggest that developing an adequate epidemiologic case definition based on
      current diagnostic criteria is possible and is a prerequisite for further
      developing the epidemiology of ADHD. The etiology of ADHD is not known but recent
      studies suggest both a strong genetic link as well as environmental factors such
      as history of preterm delivery and perhaps, maternal smoking during pregnancy.
      Children and teenagers with ADHD use health and mental health services more often
      than their peers and engage in more health threatening behaviors such as smoking,
      and alcohol and substance abuse. Better methods are needed for monitoring the
      prevalence and understanding the public health implications of ADHD. Stimulant
      medication is the treatment of choice for treating ADHD but psychosocial
      interventions may also be warranted if comordid disorders are present. The
      treatment of ADHD is controversial because of the high prevalence of medication
      treatment. Epidemiologic studies could clarify whether the patterns of ADHD
      diagnosis and treatment in community settings is appropriate. Population-based
      epidemiologic studies may shed important new light on how we understand ADHD, its
      natural history, its treatment and its consequences.

PMID- 12216061
TI  - The epidemiology of the epilepsies in children.
AB  - The epilepsies are a heterogeneous collection of neurological conditions and
      syndromes characterized by recurrent, unprovoked, paroxysmal seizure activity.
      There are several types of epileptic seizures and syndromes that are unique to
      children, including infantile spasms, Lennox-Gastaut syndrome and absence
      seizures. Febrile seizures and neonatal seizures, while not epilepsy, are
      relatively common types of seizures in infants and children and are likely
      markers of risk of later epilepsy. Thus, it is important to consider the
      epidemiological features of the epilepsies as they occur specifically in infants
      and children. The purpose of this review is to summarize what is currently known
      about the epidemiology of the childhood epilepsies and to identify promising
      areas for further population-based studies. The epilepsies are an important cause
      of neurological morbidity in children. The average annual rate of new cases
      (incidence) of epilepsy is approximately 5-7 cases per 10,000 children from birth
      to age 15 years, and in any given year, about 5 of every 1,000 children will have
      epilepsy. There is evidence that the incidence of the epilepsies in some
      populations of children may be decreasing over time, and this possibility merits
      further investigation. Factors that are known to increase risk of the epilepsies
      in children include congenital malformations of the central nervous system (CNS),
      moderate or severe head trauma, CNS infections, certain inherited metabolic
      conditions, and genetic factors. However, these account for only 25% to 45% of
      cases, and thus, the etiology of most cases of the epilepsies remains obscure.
      The paucity of well-controlled etiological studies is due largely to formidable
      methodological problems in conducting epidemiological studies of the epilepsies.
      The prognosis for seizure control is generally good, although children with
      remote symptomatic seizures and those with additional neurological disabilities
      do less well.

PMID- 12216062
TI  - Co-occurrence of developmental disabilities with birth defects.
AB  - This article begins with a discussion of the concepts of comorbidity and co
      occurrence of diseases and health conditions. These concepts are then applied to
      the literature on the population-based prevalence of developmental disabilities
      and birth defects. Most of the existing literature focuses on co-occurrence and
      obtains data from both clinical and administrative sources. Developmental
      disabilities occur more frequently in children with multiple, rather than with
      isolated, birth defects. More research, with more sophisticated study designs,
      will be necessary to further elucidate the contributions of birth defects to the
      etiology of developmental disabilities, control for other risk factors, and to
      identify strategies for prevention and intervention services.

PMID- 12216063
TI  - Environmental factors associated with a spectrum of neurodevelopmental deficits.
AB  - A number of environmental agents have been shown to demonstrate neurotoxic
      effects either in human or laboratory animal studies. Critical windows of
      vulnerability to the effects of these agents occur both pre- and postnatally. The
      nervous system is relatively unique in that different parts are responsible for
      different functional domains, and these develop at different times (e.g., motor
      control, sensory, intelligence and attention). In addition, the many cell types
      in the brain have different windows of vulnerability with varying sensitivities
      to environmental agents. This review focuses on two environmental agents, lead
      and methylmercury, to illustrate the neurobehavioral and cognitive effects that
      can result from early life exposures. Special attention is paid to distinguishing
      between the effects detected following episodes of poisoning and those detected
      following lower dose exposures. Perinatal and childhood exposure to high doses of
      lead results in encephalopathy and convulsions. Lower-dose lead exposures have
      been associated with impairment in intellectual function and attention. At high
      levels of prenatal exposure, methylmercury produces mental retardation, cerebral
      palsy and visual and auditory deficits in children of exposed mothers. At lower
      levels of methylmercury exposure, the effects in children have been more subtle.
      Other environmental neurotoxicants that have been shown to produce developmental
      neurotoxicity include polychlorinated biphenyls (PCBs), dioxins, pesticides,
      ionizing radiation, environmental tobacco smoke, and maternal use of alcohol,
      tobacco, marijuana and cocaine. Exposure to environmental agents with neurotoxic
      effects can result in a spectrum of adverse outcomes from severe mental
      retardation and disability to more subtle changes in function depending on the
      timing and dose of the chemical agent.

PMID- 12216064
TI  - Secondary conditions in children with disabilities: spina bifida as a case
      example.
AB  - This paper examines the concept of secondary conditions and its application in
      studies of childhood disability focusing on children with spina bifida as a
      representative group. The "International Classification of Functioning,
      Disability and Health" (World Health Organization, Geneva, 2001) provides a
      classification of body function/structure, activities, participation and the
      environment to document dimensions of human functioning in context. The ICF is of
      value in the study of secondary conditions in two ways: as a conceptual framework
      for defining impairments, activity limitations and participation restrictions,
      and the mediating role of the environment in their expression; and as a taxonomy
      for coding these dimensions of disability. The ICF can yield a profile of a
      child's difficulties, and documentation of environmental barriers experienced by
      that child. Research studies with children and adolescents with spina bifida
      reveal that physical and mental impairments and limitations in performing
      activities and participating in communal life are experienced as secondary
      conditions. The significance of secondary conditions is that they are
      preventable. Identifying the mechanisms associated with their manifestation is
      thus an important priority for the development of effective prevention programs.

PMID- 12216065
TI  - The epidemiology of developmental disabilities in low-income countries.
AB  - Although most of the world's children live in developing countries and may be at
      high risk for disability, very little is known about the prevalence and causes of
      developmental disabilities in these countries. This paper discusses
      methodological difficulties contributing to this lack of knowledge, and provides
      an overview of what is known about the epidemiology of developmental disabilities
      in low-income countries. At least some forms of developmental disability appear
      to be more common in low-income countries than in wealthier countries, despite
      the probability of higher mortality among children with disabilities in low
      income countries. For example, most studies of severe mental retardation in low
      income countries report prevalences greater than 5 per 1,000 children, while
      prevalence estimates from industrialized countries are consistently below this.
      Major risk factors for developmental disabilities in some low-income countries
      include specific genetic diseases, a higher frequency of births to older mothers,
      consanguinity, and specific micronutrient deficiencies and infections. Trauma and
      toxic exposures are also important risk factors, but their contributions to the
      etiology of developmental disabilities in low-income countries are not well
      documented. Though many of the causes of developmental disabilities are
      understood and preventable, proven methods of prevention are not being fully
      implemented in developing countries. Epidemiologic studies are needed to raise
      awareness of the public health impacts of developmental disabilities in low
      income countries and to provide a basis for setting priorities and designing
      efficient interventions.

PMID- 12216066
TI  - Are there two sides to colorectal cancer?
AB  - Colorectal carcinomas (CRC) that arise proximal (right) or distal (left) to the
      splenic flexure exhibit differences in incidence according to geographic region,
      age and gender. Together with observations that tumours in the hereditary cancer
      syndromes HNPCC and FAP occur predominantly in the right and left colon,
      respectively, the existence of 2 categories of CRC based on site of origin in the
      large bowel was proposed more than a decade ago. Differences between normal right
      and left colonic segments that could favour progression through different
      tumourigenic pathways are summarized in this review. Accumulating evidence
      suggests that the risk of CRC conferred by various environmental and genetic
      factors is different for proximal and distal tumours. Right- and left-sided
      tumours also exhibit different sensitivities to fluorouracil-based chemotherapy.
      Such differences are probably related to the molecular characteristics of the
      tumours, with the microsatellite instability and CpG island methylator phenotypes
      being associated with right-sided tumours and chromosomal instability with left
      sided tumours. Future molecular-based classification systems for CRC that rely
      upon distinctive gene expression patterns may allow a clearer discrimination of
      subgroups than that provided by tumour site alone. Until then however, the
      existence of 2 broadly different groups of cancer defined by site of origin in
      the colon should be considered in the design of future epidemiologic studies as
      well as in the design of new clinical trials aimed at testing novel adjuvant
      therapies.

PMID- 12216067
TI  - Neuropilin-1 is differentially expressed in myoepithelial cells and vascular
      smooth muscle cells in preneoplastic and neoplastic human breast: a possible
      marker for the progression of breast cancer.
AB  - The expression and distribution of neuropilin-1 (NRP-1) was examined in the
      samples of normal human breast tissues and in non-neoplastic and neoplastic areas
      of breast tissue removed for carcinoma using RT-PCR as well as conventional and
      tissue microarrays immunohistochemical analyses. The NRP-1 mRNA expression was
      significantly higher in neoplastic tissues as compared to normal breast samples.
      Immunohistochemically, the myoepithelial cells of the mammary ducts and lobules
      display positive reactions for NRP-1, whereas the inner ductal and lobular
      epithelial cell layers failed to react. The myoepithelial cells of ducts and
      lobules in both neoplastic and non-neoplastic tissue specimens displayed a
      stronger positive reaction for NRP-1 than those in the normal breast. A positive
      reaction for NRP-1, but with a gradual reduction in intensity, was observed in
      the myoepithelial cells of ducts with atypical epithelial hyperplasia and ductal
      carcinoma in situ (DCIS). The reaction was undetected or minimally detected in
      the areas of invasive carcinoma. NRP-1 positive immunolabeling was also localized
      in the vascular smooth muscle cells and in some endothelial cells of the blood
      vessels in normal, non-neoplastic and neoplastic breast tissue samples. In areas
      of breast carcinoma, NRP-1 immunolabeling was more prominent in both vascular
      smooth muscle cells and in some endothelial cells than in similar cells in normal
      breast. The specificity of the newly developed antibody for NRP-1 was confirmed
      by in situ hybridization with DIG-labeled PCR generated probe. These results
      suggest that NRP-1 may be a multiple function protein in human breast and may be
      involved in the induction of local invasiveness of neoplasia and angiogenesis and
      have direct relevance to the progression of breast cancer.

PMID- 12216068
TI  - Lipopolysaccharide-induced metastatic growth is associated with increased
      angiogenesis, vascular permeability and tumor cell invasion.
AB  - Endotoxin/lipopolysaccharide (LPS), a cell wall component of Gram-negative
      bacteria, is a potent inflammatory stimulus. We previously reported that LPS
      increased the growth of experimental metastases in a murine tumor model. Here, we
      examined the effect of LPS exposure on key determinants of metastasis
      angiogenesis, tumor cell invasion, vascular permeability, nitric oxide synthase
      (NOS) and matrix metalloproteinase 2 (MMP2) expression. BALB/c mice bearing 4T1
      lung metastases were given an intraperitoneal (i.p.) injection of 10 microg LPS
      or saline. LPS exposure resulted in increased lung weight and incidence of
      pleural lesions. LPS increased angiogenesis both in vivo and in vitro. Vascular
      permeability in lung tissue was increased 18 hr after LPS injection. LPS
      increased inducible nitric oxide synthase (iNOS) and MMP2 expression in lung
      tumor nodules. 4T1 cells transfected with green fluorescent protein (4T1-GFP)
      were injected via lateral tail vein. LPS exposure resulted in increased numbers
      of 4T1-GFP cells in mouse lung tissue compared to saline controls, an effect
      blocked by the competitive NOS inhibitor, N(G) methyl-L-arginine (NMA). LPS
      induced growth and metastasis of 4T1 experimental lung metastases is associated
      with increased angiogenesis, vascular permeability and tumor cell
      invasion/migration with iNOS expression implicated in LPS-induced metastasis.

PMID- 12216069
TI  - Isotype switch-mediated CH deletions are a recurrent feature of Myc/CH
      translocations in peritoneal plasmacytomas in mice.
AB  - Oncogene activating chromosomal translocations that interrupt IGH switch (S)
      regions at 14q32 are thought to be caused by misguided IGH isotype switching in
      postgerminal center B-cell lymphomas and plasma cell myelomas in humans. Aberrant
      switching also seems to be involved in altering the fine structure of the
      translocation in some of these tumors, but the significance of these changes is
      not known. Here we report on 3 cases of IL-6 transgenic mouse plasmacytomas (PCT)
      that harbor T(12;15) translocations that had been modified by frustrated switch
      attempts that result in C(H) deletions. When considered together with 6 similar
      cases of PCT described previously, our observations suggest that secondary
      deletions in C(H) are a regular feature in the molecular evolution of T(12;15)
      translocations and, thereby, in the progression of PCT. We propose that the
      T(12;15)(+) mouse PCT offers a uniquely valuable model system for elucidating the
      dual role of abnormal isotype switching in causation and 'remodeling' of
      chromosomal translocations.

PMID- 12216070
TI  - Genetic alterations in cervical carcinomas: frequent low-level amplifications of
      oncogenes are associated with human papillomavirus infection.
AB  - The development of cervical carcinoma is closely associated with HPV infection.
      However, other genetic alterations also play an important role. In this study, we
      analyzed copy number alterations of several oncogene loci in a panel of 84
      cervical tumors. Sixty-five (77%) tumors were HPV DNA-positive, and most were
      infected with type 16 or type 18 or both. The oncogenes studied include PIK3CA at
      3q26.3, TERT at 5p15.33, C-MYC at 8q24, CCND1 at 11q13.3, ERBB2 at 17q21.2 and
      locus region 20q13.2. Amplification of 1 or more genes was detected in 55 (65%)
      cases using interphase FISH. PIK3CA was amplified in 43% of tumors, followed by
      TERT (33%), 20q13.2 (30%), ERBB2 (29%), C-MYC (25%) and CCND1 (12%). Most tumors
      showed low-level amplification with 3-7 copies of these genes, and complex
      changes involving 3 or more genes occur more frequently in tumors at advanced
      stages. Increased protein expression of c-erbB2 and c-myc was observed in tumors
      with the corresponding gene amplification. Oncogene alterations were found more
      often in HPV-infected cases, particularly for C-MYC and TERT. These findings
      indicate that HPV-associated cervical carcinomas bear frequent alterations of
      these genes, which may have critical biologic impact on the development and
      progression of carcinoma of the uterine cervix.

PMID- 12216071
TI  - E-cadherin gene variants in gastric cancer families whose probands are diagnosed
      with diffuse gastric cancer.
AB  - To identify germline E-cadherin mutations responsible for the predisposition to
      diffuse gastric cancer (DGC) among the Japanese, we screened 17 patients with
      familial aggregation of gastric cancer by sequencing analysis. All the patients
      were diagnosed with DGC and had at least 1 sibling with gastric cancer. Two novel
      E-cadherin gene variants were detected. One was detected in 1 patient only and
      associated with an amino acid substitution (Val/Met) at codon 832 in the region
      essential for binding to beta-catenin. The M832 variant was detected not only in
      the proband but also in 2 other gastric cancer patients in the family.
      Immunohistochemical analysis of gastric cancer tissue from the proband revealed
      that E-cadherin expression was markedly reduced and beta-catenin expression was
      also reduced in cancer cells. However, no significant difference in the activity
      of beta-catenin binding was detected between the M832 variant and V832 wild-type
      E-cadherin in immunofluorescence and immunoprecipitation/Western blot analyses.
      The other was detected in 5 patients and was located in the splice donor site
      (IVS1+6T/C); however, RT-PCR analysis indicated that the IVS+6C variant did not
      cause an aberrant splicing. Thus, the M832 variant could be a germline mutation
      causative of familial aggregation of DGC, although further functional studies are
      needed to understand the pathogenic significance of this variant.

PMID- 12216072
TI  - Epstein-Barr virus antagonizes the antiproliferative activity of transforming
      growth factor-beta but does not abolish its signaling.
AB  - TGF-beta induces apoptosis and inhibits the proliferation of EBV-negative B
      lymphoma cell lines. In contrast, EBV-immortalized B cells are resistant to both
      the proapoptotic and the antiproliferative activities of TGF-beta. We have
      generated a lymphoblastoid cell line, in which we can switch on and off the EBV
      specific transcriptional program driven by EBNA2. When these cells express the
      EBNA2-driven phenotype, they are resistant to TGF-beta-mediated growth arrest. We
      used this cell line to readdress the question of how EBV can overcome the
      antiproliferative TGF-beta activity. We show here that EBV-driven cells remain
      TGF-beta-responsive since TGF-beta target genes are readily induced. Thus, EBV
      can overcome TGF-beta-mediated growth arrest without interfering with the core
      machinery of the TGF-beta signaling pathway, which links ligand binding to the
      induction of TGF-beta target genes.

PMID- 12216073
TI  - The SSX gene family: characterization of 9 complete genes.
AB  - Human SSX genes comprise a gene family with 6 known members. SSX1, 2 and 4 have
      been found to be involved in the t(X;18) translocation characteristically found
      in all synovial sarcomas. Four (SSX1, 2, 4 and 5) are known to be expressed in a
      subset of tumors and testis, and anti-SSX antibodies have been found in sera from
      cancer patients. SSX antigens are thus typical cancer-testis (CT) antigens. To
      identify additional SSX family members, we isolated and characterized human
      genomic clones homologous to a prototype SSX cDNA. We also searched public
      databases for sequences similar to SSX. This identified 3 additional SSX genes,
      SSX7, 8, 9, and also completed the sequence of the formerly partially defined
      SSX6 gene. In addition to these novel SSX genes, several SSX pseudogenes were
      identified. With the exception of 1 pseudogene, all SSX genomic SSX sequences map
      to chromosome X. Among normal tissues, SSX7 mRNA was present only in testis,
      whereas SSX6, 8 and 9 were not detected in any normal tissue. SSX6 and 7 were
      expressed in 1 of 9 melanoma cell lines tested, whereas SSX8 and 9 expression was
      not detected in any tumor tissue or cell lines tested. SSX1, 2, 4 and 5 mRNA
      expression can be induced in cell lines by 5-aza-2-deoxycytidine or Trichostatin
      A. These agents also induce SSX6, but not SSX3, 7, 8 or 9 in the tumor cell lines
      tested, indicating that mechanisms other than methylation or histone acetylation
      may be responsible for the repressed state of some SSX genes.

PMID- 12216074
TI  - A potential role of heat shock proteins and nicotinamide N-methyl transferase in
      predicting response to radiation in bladder cancer.
AB  - The use of definitive radiotherapy for treatment of invasive bladder cancer has
      the advantage of preserving bladder function, but tumour regression is only
      achieved in approximately 40-50% of patients. Knowledge of the molecular basis of
      sensitivity to ionizing radiation and identification of potential molecular
      predictors will provide useful information regarding patient response and thus
      help clinicians to individualize treatment. The recent application of cDNA
      expression array technology provides a useful tool to investigate hundreds or
      even thousands of genes in a single experiment. In our study, we have used the
      Atlas human stress cDNA array trade mark to investigate the expression profile of
      stress-related and DNA repair genes in a radioresistant bladder carcinoma cell
      line (MGH-U1) and its radiosensitive subclone (S40b). This provides an ideal
      situation to study genes related to radiation because the genotypes of both cell
      lines are basically similar and differential changes detected are likely to be
      related to the different radiosensitivity phenotype. Of 234 genes blotted on the
      array, 3 genes (Heat shock protein 90, Heat shock protein 27 and Nicotinamide N
      methyl transferase) showed consistent downregulation in the radiosensitive clone
      in 2 independent experiments. These results were further confirmed for HSP27 and
      NNMT using Sybr Green I-based real-time QRT-PCR. The role of heat shock proteins
      (HSPs) in response to radiation remains to be determined; however, the results of
      our present work suggest a possible role of HSP27 in determining
      radiosensitivity. Our study also opens avenues for the investigation of genes,
      such as NNMT, which has not previously been linked to response to radiation.

PMID- 12216075
TI  - Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits
      azoxymethane-induced colon carcinogenesis in male F344 rats.
AB  - The modifying effect of dietary administration of the polyphenolic antioxidant
      flavonoid silymarin, isolated from milk thistle [Silybum marianum (L.)
      Gaertneri], on AOM-induced colon carcinogenesis was investigated in male F344
      rats. In the short-term study, the effects of silymarin on the development of AOM
      induced colonic ACF, being putative precursor lesions for colonic adenocarcinoma,
      were assayed to predict the modifying effects of dietary silymarin on colon
      tumorigenesis. Also, the activity of detoxifying enzymes (GST and QR) in liver
      and colonic mucosa was determined in rats gavaged with silymarin. Subsequently,
      the possible inhibitory effects of dietary feeding of silymarin on AOM-induced
      colon carcinogenesis were evaluated using a long-term animal experiment. In the
      short-term study, dietary administration of silymarin (100, 500 and 1,000 ppm in
      diet), either during or after carcinogen exposure, for 4 weeks caused significant
      reduction in the frequency of colonic ACF in a dose-dependent manner. Silymarin
      given by gavage elevated the activity of detoxifying enzymes in both organs. In
      the long-term experiment, dietary feeding of silymarin (100 and 500 ppm) during
      the initiation or postinitiation phase of AOM-induced colon carcinogenesis
      reduced the incidence and multiplicity of colonic adenocarcinoma. The inhibition
      by feeding with 500 ppm silymarin was significant (p < 0.05 by initiation feeding
      and p < 0.01 by postinitiation feeding). Also, silymarin administration in the
      diet lowered the PCNA labeling index and increased the number of apoptotic cells
      in adenocarcinoma. beta-Glucuronidase activity, PGE(2) level and polyamine
      content were decreased in colonic mucosa. These results clearly indicate a
      chemopreventive ability of dietary silymarin against chemically induced colon
      tumorigenesis and will provide a scientific basis for progression to clinical
      trials of the chemoprevention of human colon cancer.

PMID- 12216076
TI  - Role of Helicobacter pylori infection among offspring or siblings of gastric
      cancer patients.
AB  - A positive family history is an increased risk factor for gastric cancer within
      family members, and one of the possible causes of this is the intrafamilial
      clustering of Helicobacter pylori infection. Our study examined the prevalence of
      H. pylori infection, serum antibodies to CagA and VacA and atrophic gastritis
      and/or intestinal metaplasia in the offspring or siblings of gastric cancer
      patients. A total of 726 subjects included 300 relatives of 300 separate gastric
      cancer patients and 426 controls. All subjects underwent upper gastrointestinal
      endoscopic examination with a rapid urease test. Blood samples were obtained to
      test for the presence of serum antibodies to the CagA and VacA proteins of H.
      pylori. The prevalence of H. pylori infection was higher in relatives of cancer
      patients (75.3%) than in controls (60.1%), and the adjusted odds ratio was 2.1
      (95% CI 1.5-2.9). When either siblings or 2 or more family members were gastric
      cancer patients, the prevalence of H. pylori infection was much higher compared
      to the prevalence in controls. There was no specific relationship between CagA
      and VacA, and H. pylori infection. Atrophic gastritis and/or intestinal
      metaplasia were more frequently found in H. pylori-infected relatives of cancer
      patients (26.1%) than in H. pylori-infected controls (12.9%). These results
      strongly support a role for H. pylori infection in familial aggregation of
      gastric cancer. The prophylactic eradication of H. pylori infection in the
      offspring or siblings of gastric cancer patients may be clinically beneficial.

PMID- 12216077
TI  - Interval cancers following breast cancer screening in Singaporean women.
AB  - Our study reports on the interval cancers arising in the subsequent 3 years in
      women screened as part of the Singapore Breast Cancer Screening Programme that
      commenced in 1994. Women, the majority of Chinese ethnicity, were either invited
      or not invited by random allocation to be screened. All women, other than those
      identified with breast cancer at screening, whether invited or not, were followed
      for 3 years, and information on all breast cancers arising in this period was
      obtained through the national registry. In particular, the cancers arising from
      those women who were deemed free of the disease at screening were noted. The
      mammographs taken at screening of those women who developed such an interval
      cancer were rereviewed by 3 radiologists. In the 28,099 women who were screened
      and deemed free of disease, 59 interval cancers were reported with annual rates
      of 2.1, 10.6 and 10.8 per 10,000 women-years in the succeeding 3-year periods. In
      39,425 women who were invited but declined screening, the rates were 17.0, 15.5
      and 11.7, while the corresponding rates from 97,294 women not invited were 12.8,
      13.3 and 13.0. Whereas the annual incidence at 1 year in women who have been
      screened is much lower than those in the 2 groups who were not screened, it is of
      a similar magnitude by 2 years. This suggests that locally an optimal screening
      interval may be close to 1 year. The rereview of the mammograms of those 59 women
      with interval cancers suggested that the maximum possible number of these that
      might have been detected at screening was 10 (17%).

PMID- 12216078
TI  - In vivo evaluation of 188Re-labeled alpha-melanocyte stimulating hormone peptide
      analogs for melanoma therapy.
AB  - The purpose of our study was to optimize melanoma tumor uptake of 188Re-CCMSH and
      reduce its nonspecific kidney retention. Nephrotoxicity is often a serious
      problem associated with targeted radiotherapy, therefore, increasing the
      tumor/kidney uptake ratio of 188Re-CCMSH is crucial for optimizing its
      therapeutic efficacy. Structural modification of the peptide and amino acid co
      infusion were investigated as strategies to improve the tumor/kidney uptake ratio
      of 188Re-CCMSH. The substitution of Lys11 with Arg11 was examined to determine if
      removal of lysine from the peptide would improve kidney clearance without
      sacrificing tumor uptake. The pharmacokinetics of 188Re-CCMSH and 188Re
      (Arg(11))CCMSH were determined in B16/F1 murine melanoma-bearing C57 mice. Tumor
      uptake values of (188)Re-CCMSH and 188Re-(Arg(11))CCMSH were 15.03 +/- 5.20% ID/g
      and 20.44 +/- 1.91% ID/g at 1 hr postinjection and 1.94 +/- 0.47% ID/g and 3.50
      +/- 2.32% ID/g at 24 hr postinjection. Renal retention of 188Re-(Arg(11))CCMSH
      was 11.79 +/- 1.29 ID/g and 3.67 +/- 0.51 ID/g at 1 hr and 4 hr postinjection,
      which was a greater than 50% reduction compared to 188Re-CCMSH. The Arg for Lys
      substitution in 188Re-(Arg(11))CCMSH resulted in improved tumor uptake and
      reduced kidney retention. Renal retention of both 188Re-CCMSH and 188Re
      (Arg(11))CCMSH were significantly reduced by co-injection of 20 mg of L-lysine, L
      arginine and a combination of L-lysine:L-arginine. Tumor/kidney uptake values for
      188Re-CCMSH and 188Re-(Arg(11))CCMSH were maximally reduced by 52.9% and 46.3%,
      respectively. However, even with amino acid co-injection, the tumor/kidney ratio
      of 188Re-CCMSH was lower than that of 188Re-(Arg(11))CCMSH. Improved tumor uptake
      and reduced kidney retention of 188Re-(Arg(11))CCMSH will facilitate targeted
      irradiation of melanoma tumors while minimizing the dose to the kidneys.

PMID- 12216079
TI  - Copper-transporting P-type adenosine triphosphatase (ATP7B) as a cisplatin based
      chemoresistance marker in ovarian carcinoma: comparative analysis with expression
      of MDR1, MRP1, MRP2, LRP and BCRP.
AB  - Intrinsic or acquired resistance to chemotherapy is the major obstacle to
      overcome in the treatment of patients with solid carcinoma. Cisplatin is one of
      the most effective chemotherapeutic agents for treating ovarian carcinoma.
      Recently, copper-transporting P-type adenosine triphosphatase (ATP7B) has been
      demonstrated as one of the genes responsible for cisplatin resistance in vitro.
      We hypothesized that the expression of ATP7B gene increases resistance to
      cisplatin in ovarian carcinoma and a priori knowledge of its expression is
      important for the choice of therapy. The aim of our study was to assess the role
      of ATP7B gene in ovarian carcinoma and compare its expression with those of
      multidrug resistance-related transporters such as MDR1, MRP1, MRP2, LRP and BCRP
      genes. The transporters' gene expression profiles from 82 patients treated with
      cisplatin-based chemotherapy after surgery were assessed by RT-PCR. We did not
      observe any significant correlation between ATP7B gene expression and those of
      MDR1, MRP1, MRP2, LRP or BCRP. The expression level of ATP7B gene was
      significantly increased (p < 0.05) in patients with moderately-/poorly
      differentiated ovarian carcinomas treated with cisplatin-based chemotherapy, thus
      ATP7B may serve as an independent prognostic factor in these patients. In
      contrast, the expression level of MDR1, MRP1, MRP2, LRP and BCRP genes were not
      prognostic indicators of disease. These findings suggest that ATP7B gene may be
      considered as a novel chemoresistance marker and that inhibitor(s) of ATP7B might
      be useful, in patients with ovarian carcinoma treated with cisplatin-based
      chemotherapy.

PMID- 12216080
TI  - Phenylbutyrate inhibits the invasive properties of prostate and breast cancer
      cell lines in the sea urchin embryo basement membrane invasion assay.
AB  - Histone deacetylase inhibitors, such as phenylbutyrate, are currently undergoing
      clinical trials as potential anticancer agents. Phenylbutyrate can induce cell
      differentiation and apoptosis in a number of cancer cell types and can act in
      synergy with ionizing radiation and chemotherapy to induce apoptosis. We used the
      sea urchin embryo basement membrane invasion assay to show that phenylbutyrate
      potently inhibited the invasive properties of both prostate and breast cancer
      cells at clinically achievable doses. This inhibition was dose-dependent and
      persisted for at least 24 hr after the drug was removed. These results suggest
      that in addition to activating apoptosis in cancer cells, phenylbutyrate may be
      used in prevention of metastatic disease.

PMID- 12216081
TI  - Is aristolochic acid a risk factor for Balkan endemic nephropathy-associated
      urothelial cancer?

PMID- 12216083
TI  - Factors that influence surgical choices in women with breast carcinoma.
AB  - BACKGROUND: In the absence of medical contraindications, survival after
      undergoing breast-conserving therapy (BCT), mastectomy (M), and mastectomy with
      immediate reconstruction (MIR) is equal. The authors studied demographic factors
      to identify the variables that differed significantly among women making
      different surgical choices. METHODS: Women with ductal carcinoma in situ or
      clinical Stage I or II breast carcinoma with no contraindications for BCT or MIR
      who were treated between 1995 and 1998 were identified from a prospectively
      collected data base. Demographic and tumor factors were compared using the Fisher
      exact test. RESULTS: There were 578 women with 586 tumors who did not have
      contraindications for BCT or MIR. Among this group, 85.2% of women chose BCT,
      9.2% of women chose M, and 5.6% of women chose MIR. Women undergoing M alone were
      older and were more likely to have Stage II carcinoma compared with women
      undergoing BCT. Patients undergoing M or MIR were more likely to have had a prior
      breast biopsy compared with patients who chose BCT. Marital status and employment
      approached significance (P = 0.06); however, a family history of breast carcinoma
      was not a predictor of treatment choice. CONCLUSIONS: The current findings
      suggest a need for patient education strategies that emphasize the lack of
      influence of age and prior breast biopsy on the use of BCT. Differences in
      demographic variables may reflect true variations in patient preference among
      groups, emphasizing the need to address the spectrum of treatment options with
      patients.

PMID- 12216084
TI  - Expression of endothelial and inducible nitric oxide synthase in benign and
      malignant lesions of the breast and measurement of nitric oxide using electron
      paramagnetic resonance spectroscopy.
AB  - BACKGROUND: Nitric oxide (NO) is present in various human solid tumors and tumor
      cell lines, and it is believed that NO plays an important role in tumor growth.
      An increased NO concentration catalyzed by NO synthase (NOS) is cytotoxic and can
      promote apoptosis. The expression of endothelial NOS (e-NOS) and induced NOS (i
      NOS) was examined in various breast tumors. METHODS: Immunohistochemical staining
      with a monoclonal antibody (Ab) against e-NOS and a polyclonal Ab against i-NOS
      was performed on paraffin embedded tissues from 41 benign breast lesions, 9 in
      situ breast lesions, and 54 invasive breast lesions. Functionality was confirmed
      by detection of NO using spin-trapping electron paramagnetic resonance (EPR)
      spectroscopy. RESULTS: e-NOS expression was found in 2 benign lesions (5%; 1
      fibroadenoma and 1 proliferative mastopathy), in 5 in situ lesions (56%), and in
      33 invasive lesions (61%). None of the benign lesions was positive for i-NOS, but
      6 in situ lesions (67%) and 33 invasive lesions (61%) showed tumor cell staining.
      In particular, capillaries that were embedded in lymphocytic stroma showed a
      positive reaction for e-NOS. The functionality of NOS was demonstrated by direct
      NO formation using the EPR spin-trapping method. Tumors that were positive for e
      NOS were observed more often in younger patients (P = 0.05). These tumors more
      frequently were highly differentiated or moderately differentiated and more often
      showed invasive ductal subtypes and a lower proliferation rate. Tumors that were
      positive for both e-NOS and i-NOS were more likely to be lymph node negative
      tumors. Both i-NOS-expressing lesions and e-NOS-expressing lesions showed strong
      coexpression (P = 0.00001). CONCLUSIONS: NOS is detected predominantly in in situ
      lesions and invasive breast lesions but rarely in benign lesions. NOS is found
      more frequently in invasive carcinomas with low malignancy. Using the spin
      trapping EPR method, this study demonstrates direct NO formation in human breast
      tumors for the first time.

PMID- 12216085
TI  - The expression pattern of Ku correlates with tumor radiosensitivity and disease
      free survival in patients with rectal carcinoma.
AB  - BACKGROUND: Preoperative radiotherapy reduces the rate of local recurrence and
      improves the chance of survival in patients with resectable, advanced rectal
      carcinoma. However, because not all tumors respond similarly to radiation,
      sorting out suitable patients is required to irradiate tumors rationally. The
      authors examined the possible role of Ku protein in determining tumor
      radiosensitivity and disease free survival in patients with rectal carcinoma.
      METHODS: The authors studied 96 patients with advanced rectal carcinoma. In
      preradiation biopsy specimens of tumor samples, the number of cells that were
      stained positive for Ku protein was evaluated by immunohistochemistry. The
      expression pattern of Ku protein was examined for an association between tumor
      radiosensitivity (which was determined according to T classification downstaging,
      complete pathologic response, or Response Evaluation Criteria in Solid Tumors)
      and disease free survival. RESULTS: There was a high degree of correlation
      between the percentage of cells that expressed the 70-kDa Ku protein (Ku70) and
      the 86-kDa Ku protein (Ku86) in the tumor sections (correlation coefficient =
      0.85; P < 0.001). The expression pattern of Ku protein was correlated not only
      with tumor radiosensitivity but also with disease free survival. Pathologic TMN
      classification, histopathologic grade, and Ku70 expression were significant
      prognostic variables for disease free survival in a multivariate analysis (P =
      0.0031, P = 0.030, and P = 0.023, respectively). CONCLUSIONS: Ku70 and Ku86 raise
      the predictive possibility of tumor radiosensitivity. Ku may be a useful
      parameter for selecting patients with rectal carcinoma for preoperative
      radiotherapy.

PMID- 12216086
TI  - Curcumin inhibits interleukin 8 production and enhances interleukin 8 receptor
      expression on the cell surface:impact on human pancreatic carcinoma cell growth
      by autocrine regulation.
AB  - BACKGROUND: Curcumin, the yellow pigment in turmeric, has been shown to prevent
      tumor progression in a variety of tissues in rodents. The authors investigated
      the effect of curcumin on human carcinoma cell lines to determine whether
      constitutive interleukin-8 (IL-8) production of tumor cells was correlated with
      nuclear factor kappaB (NF-kappaB) activation and cell growth activity. METHODS: A
      human pancreatic carcinoma cell line, SUIT-2, was incubated with various
      concentrations of curcumin for 2 hours. Biologic features, including IL-8
      production, DNA binding activity, transactivation of NF-kappaB, cell growth
      activity, cell viability, and the expression of IL-8 receptors (CXCR1 and CXCR2)
      were analyzed. RESULTS: The constitutive production of IL-8 was inhibited by
      curcumin at concentrations of 10-100 microM in a dose dependent manner. NF-kappaB
      activity was reduced significantly by curcumin treatment. Pretreatment with
      curcumin inhibited the growth rate of carcinoma cells significantly. Such cell
      growth inhibition by curcumin was not recovered by exogenous recombinant IL-8.
      The investigation of expression in IL-8 receptors, CXCR1 and CXCR2, revealed that
      the expression of both receptors was enhanced remarkably by curcumin. Exogenous
      IL-8 could not recover this enhancement of IL-8 receptors. These results suggest
      that curcumin inhibits IL-8-induced receptor internalization. CONCLUSIONS: The
      authors concluded that curcumin contributed not only to the inhibition of IL-8
      production but also to signal transduction through IL-8 receptors. These data
      suggest that curcumin reduces numerous IL-8 bioactivities that contribute to
      tumor growth and carcinoma cell viability. From this point of view, curcumin is a
      potent anticancer agent that inhibits the production of proinflammatory
      cytokines, including IL-8, by tumor cells.

PMID- 12216087
TI  - Prognostic significance of positive surgical margins in patients with
      extraprostatic carcinoma after radical prostatectomy.
AB  - BACKGROUND: A significant number of prostate adenocarcinoma patients undergoing
      radical prostatectomy are found to have microscopic extraprostatic disease
      extension. A majority of these patients have focal extraprostatic extension
      limited to one or both sides of the prostate. In addition, positive surgical
      margins are a common pathologic finding in this patient subgroup. In the current
      study, the authors evaluated the impact of positive surgical margins as an
      independent predictive factor for prostate specific antigen (PSA) progression in
      patients with pT3a/b N0M0 carcinoma. METHODS: The Mayo Clinic prostate cancer
      registry list provided 1202 patients with pT3a/b NO prostate carcinoma (no
      seminal vesicle or regional lymph node involvement) who underwent a radical
      prostatectomy between 1987-1995. To reduce confounding variables, patients who
      received preoperative therapy or adjuvant therapy were excluded, resulting in 842
      patients who were eligible for analysis. RESULTS: A total of 354 patients (42%)
      had > or = 1 positive surgical margins whereas 488 patients (58%) demonstrated no
      margin involvement. The sites of margin positivity were as follows: apex (n =
      163), base (n = 47), posterior prostate (n = 227), and anterior prostate (n =
      11). A total of 111 patients had > or = 2 positive surgical margins. The 5-year
      survival free of clinical recurrence and/or biochemical failure (postoperative
      PSA level > 0.2 ng/mL) for patients with no positive surgical margins was 76% and
      was 65% for patients with 1 positive surgical margin (P = 0.0001). There was no
      significant difference in biochemical disease progression between patients with 1
      versus those with > or = 2 surgical margins (65% vs. 62%). Multivariate analysis
      revealed that positive surgical margins were a significant predictor (P = 0.0017)
      of clinical disease recurrence and biochemical failure (relative risk, 1.55; 95%
      confidence interval, 1.18-2.04) after controlling for preoperative PSA, Gleason
      score, and DNA ploidy. CONCLUSIONS: In the current study, positive surgical
      margins were found to be a significant predictor of disease recurrence in
      patients with pT3a/b NO prostate carcinoma, a finding that is independent of PSA,
      Gleason score, and DNA ploidy. The benefit of adjuvant therapy in optimizing
      recurrence-free survival remains to be tested.

PMID- 12216088
TI  - Phase I trial of interferon alpha2b and liposome-encapsulated all-trans retinoic
      acid in the treatment of patients with advanced renal cell carcinoma.
AB  - BACKGROUND: Studies suggest that retinoic acid (RA) can augment the antitumor
      effects of interferon-based therapy in patients with advanced renal cell
      carcinoma (RC); however, this benefit has not been achieved convincingly using
      oral formulations of 13-cis RA and all-trans RA. Liposome-encapsulated all-trans
      RA (ATRA-IV) has improved pharmacokinetics with increased and prolonged ATRA
      serum levels compared with oral retinoids. METHODS: Cohorts of 3-6 patients with
      progressive metastatic RC received a dose of 3 MU interferon alpha2b per day
      subcutaneously, which was escalated weekly to 5 MU and then to 10 MU, plus ATRA
      IV beginning at a dose of 90 mg/m(2) intravenously three times per week (Monday,
      Wednesday, and Friday), with a planned escalation to a maximum of 140 mg/m(2).
      RESULTS: Two of the initial five patients experienced Grade 3 leukopenia while
      receiving 3 MU interferon and 90 mg/m(2) ATRA-IV. Therefore, the trial was
      amended to begin ATRA-IV at a dose of 15 mg/m(2) three times per week with a
      planned escalation by 15 mg/m(2) per cohort plus interferon-alpha at a dose of 3
      MU subcutaneously 5 days per week (Monday through Friday), which was escalated
      weekly to 5 MU and then to 10 MU. Twelve patients were treated on the revised
      schedule. Toxicity was mild and included Grade 2 anemia (n = 7 patients),
      leukopenia (n = 2 patients), nausea (n = 2 patients), fatigue (n = 2 patients),
      fever (n = 2 patients), hepatic toxicity (n = 1 patient), edema (n = 1 patient),
      neurocortical toxicity (n = 1 patient), headache (n = 1 patient), and infection
      (n = 1 patient). One patient developed hyperthyroidism, and one patient required
      admission for bacteremia from a line infection. Dose limiting toxicity was Grade
      3 hepatic toxicity, which was observed at a dose of 30 mg/m(2) ATRA-IV in 2 of 6
      patients. Only 2 of 12 patients agreed to a dose escalation up to 10 MU
      interferon-alpha. Of 12 patients who were evaluable for response, 2 patients
      (17%) had a partial response in bone and lung, including 1 partial response of >
      91 weeks' duration, at a dose of 15 mg/m(2) ATRA-IV three times per week and 5 MU
      interferon-alpha. Five additional patients experienced stable disease, two of
      whom had disease progression in bone only. CONCLUSIONS: The acceptable toxicity
      profile and preliminary efficacy results suggest that this regimen warrants
      further evaluation. ATRA-IV (15 mg/m(2) TIW) and interferon-alpha (3 MU Monday
      through Friday escalated weekly to 5 MU and to 7 MU) are recommended for further
      study in patients with advanced RC.

PMID- 12216089
TI  - Bilateral testicular germ cell tumors: twenty-year experience at M. D. Anderson
      Cancer Center.
AB  - BACKGROUND: The incidence of testicular carcinoma in the United States has
      increased significantly over the last two decades. Germ cell tumors form the
      majority of malignant testicular tumors. With advances in diagnosis and
      therapeutic approaches, germ cell tumors are now highly sensitive to treatment,
      providing long-term survival. It has been speculated that the incidence of
      bilateral germ cell tumors may increase due to the improved survival of patients
      with unilateral germ cell tumors. In this report, the authors present a study of
      bilateral germ cell tumors of the testis in men who were treated at The
      University of Texas M. D. Anderson Cancer Center over a 20-year period with
      emphasis on their incidence, histologic features, and clinical features. METHODS:
      Between 1978 and 1999, 2431 patients with testicular germ cell tumors were
      treated at The University of Texas M. D. Anderson Cancer Center. Among these, 24
      patients with bilateral germ cell tumors were identified. Clinical records and
      all available pathology slides of the tumors were reviewed. RESULTS: The overall
      incidence of bilateral germ cell tumors in the patients with testicular germ cell
      tumors was 1% (24 of 2431 patients). The incidence was 1.8% (14 of 776 patients)
      in patients with seminoma and 0.6% (10 of 1655 patients) in patients with
      nonseminomatous germ cell tumors. Patients with seminoma who were age </= 30
      years at the time of initial diagnosis had a higher incidence of bilateral tumors
      compared with older men. Twenty of 24 patients with bilateral germ cell tumors
      had metachronous tumors, and 4 patients had synchronous tumors. Among the
      patients with metachronous tumors, 70% of second tumors occurred within 5 years;
      the longest interval between the first and second tumors was 15 years. The
      outcome of patients with bilateral germ cell tumors was excellent; only 1 of 24
      patients died of metastatic disease. CONCLUSIONS: The overall incidence of
      bilateral testicular germ cell tumors was 1% in patients who were treated at The
      University of Texas M. D. Anderson Cancer Center over the past two decades. The
      incidence of bilateral germ cell tumors was related to the histologic type of the
      initial tumor and to the patient's age at initial presentation in patients with
      seminoma. Thus, patients in the second or third decade of life who presented with
      seminomas as their initial tumor were more likely to develop a second germ cell
      tumor compared with patients in the fourth or fifth decade of life. These
      findings have potentially important implications for clinical management by
      identifying a population of patients with germ cell tumors who are at risk of
      developing a second tumor and also for studying risk factors of bilateral germ
      cell tumors of the testis.

PMID- 12216090
TI  - Role of 5-aminolevulinic acid in the detection of urothelial premalignant
      lesions.
AB  - BACKGROUND: The authors evaluated the role of 5-aminolevulinic acid (5-ALA)
      induced fluorescence endoscopy (AFE) in the detection of flat urothelial lesions
      in light of the suggestions made for flat neoplastic lesions within the 1999
      World Health Organization (WHO) classification of urinary bladder tumors.
      METHODS: From 1995 to 2000, 713 patients underwent 1414 AFE procedures for the
      detection of transitional cell carcinoma of the bladder (TCCB). Fluorescence
      imaging was performed with an incoherent light source (D-light; 380-440 nm) that
      was filtered for efficient protoporphyrin IX excitation and with cystoscopes
      partially blocking reflected excitation light to enable fluorescence evaluation
      by a red/blue color contrast 2-3 hours after 50 mL of a 3% solution of 5-ALA was
      instilled into the bladder. In total, 3834 biopsy specimens (mean, 2.7 specimens
      per AFE procedure) were taken. RESULTS: Malignant disease was found in 1250
      (32.6%) of all biopsies, with 304 biopsies (24.3%) showing carcinoma in situ
      (cis) and dysplasia II degrees (dys II) according to the previous diagnostic
      criteria of the WHO. Under prior conventional white-light endoscopy, 30.3% of
      specimens with dys II and 52.8% of specimens with cis had been missed.
      CONCLUSIONS: The current results suggest that 5-ALA may be more effective in the
      detection of flat urothelial lesions than the current diagnostic devices.

PMID- 12216091
TI  - Patterns of multiple recurrences of superficial (Ta/T1) transitional cell
      carcinoma of bladder and effects of clinicopathologic and biochemical factors.
AB  - BACKGROUND: Although multiple sequential recurrences are one of the most
      important characteristics of superficial transitional cell carcinoma (TCC) of the
      bladder, few studies have examined multiple sequential recurrence patterns and
      the clinicopathologic and biochemical factors associated with these patterns.
      METHODS: Two hundred seventy superficial TCC bladder carcinoma patients were
      followed. Clinical, pathologic, and tumor marker (p53, MIB-1, bcl-2, c-erb B-2,
      and epidermal growth factor receptor) data were collected at baseline and during
      followup. The Kaplan-Meier (KM) method was used to describe multiple recurrences.
      The Wei, Lin, and Weissfeld (WLW) marginal proportional hazards model was used to
      assess the effects of clinicopathologic and immunohistochemic factors on multiple
      recurrences. RESULTS: Among the 270 patients, 126 (46.7%) had one or more
      recurrences, 38 (14.1%) had two or more recurrences, and 14 (5.2%) had three or
      more recurrences during the followup. The median times for the first, the second,
      and the third recurrences were 23 months, 15 months, and 13 months, respectively.
      In KM analysis, Stage T1, higher grades, and Ki-67 stain positivity were
      associated with the first recurrence, and p53 stain positivity was marginally
      significant. Other markers were not significant. For the second recurrence, only
      p53 stain positivity was significant. In multivariate analysis (WLW method),
      stage was significantly associated with the first recurrence (risk ratio [RR] =
      2.03), and Ki-67 was marginally significant (RR = 1.49). For the second
      recurrence, only p53 positivity was statistically significant (RR = 2.73).
      CONCLUSIONS: Among superficial TCC bladder carcinoma patients, multiple
      recurrences are common phenomena. The time for recurrence becomes shorter as the
      number of recurrences increases. In addition to tumor stage and grade, Ki-67 can
      be used to identify patients at high risk for a first recurrence; and p53 can be
      used to identify patients at high risk for a second recurrence.

PMID- 12216092
TI  - Tissue microarray analysis of cytoskeletal actin-associated biomarkers gelsolin
      and E-cadherin in urothelial carcinoma.
AB  - BACKGROUND: Alterations of expression of the cytoskeletal proteins Gelsolin and E
      cadherin have been implicated in urothelial carcinoma tumorigenesis. However, it
      is not clear how these altered expressions associate with tumor progression, nor
      is it clear how these protein markers provide prognostic value for urothelial
      carcinomas. METHODS: Primary urothelial carcinoma tissue microarrays were
      constructed for 146 patients with urothelial carcinoma. Where available, four
      replicate tissue samples of invasive tumor, adjacent dysplastic and in situ
      lesions, and benign tumors were arrayed for each case, resulting in a total of
      1208 tissue spots. Immunohistochemical staining for Gelsolin, E-cadherin, p53,
      and Ki67 (MIB-1) was performed on the arrays. For each marker, the maximum
      staining intensity (Max), the percentage of positive staining (Pos), and the
      product of both Max and Pos (MaxPos) were analyzed. RESULTS: Compared with the
      benign fields, the expression of both cytoskeletal proteins decreased in
      premalignant and malignant lesions. For Gelsolin, decreased MaxPos was seen in
      premalignant and preinvasive lesions. However, with an increase in tumor grade
      and stage, there was a gradual increase in Gelsolin (P < 0.05 for both). E
      cadherin expression decreases mainly in high-grade lesions (carcinoma in situ and
      Grade 3 tumors). Univariate and multivariate analyses showed that Gelsolin Max
      was a strong independent predictor for the probability of tumor recurrence and
      for early tumor recurrence in high-grade or high-stage tumors, as well as a
      strong indicator for tumor progression. CONCLUSIONS: Gelsolin and E-cadherin have
      distinctive expression patterns. Gelsolin, but not E-cadherin, provides
      independent prognostic information for high-grade urothelial carcinomas.

PMID- 12216093
TI  - The effect of retinoids on premalignant oral lesions: focus on topical therapy.
AB  - BACKGROUND: Retinoids have been studied as chemopreventive treatment for patients
      with oropharyngeal carcinoma. Vitamin A modulates growth and differentiation of
      cells, and its deficiency enhances susceptibility to carcinogenesis. The
      chemopreventive mechanism of action of vitamin A is discussed, and a review of
      clinical results and side effects of the systemic use of vitamin A is included.
      The objective of the current report was to review the possible role of topical
      vitamin A and vitamin A derivatives in the management of patients with oral
      lesions with a risk of transformation to carcinoma. METHODS: A Medline search was
      conducted and references identified within the identified papers were also
      reviewed. RESULTS: Only four studies using topical vitamin A for patients with
      oral leukoplakia have been reported. A complete response was achieved in 10-27%
      of patients, and a partial response was achieved in 54-90% of patients; however,
      recurrence of leukoplakia was reported after withdrawing the medication in
      approximately 50% of patients. The side effects of the topical use were minimal.
      CONCLUSIONS: Although the direct application of higher concentrations of retinoic
      acid results in suppression of oral leukoplakias only, its use in the treatment
      of patients with recurrent and persistent lesions may be justified for
      controlling lesions that otherwise may progress. Further controlled clinical
      studies are needed.

PMID- 12216094
TI  - Second-line, low-dose, weekly paclitaxel in patients with stage IIIB/IV nonsmall
      cell lung carcinoma who fail first-line chemotherapy with carboplatin plus
      paclitaxel.
AB  - BACKGROUND: Second-line chemotherapy with docetaxel improves survival and quality
      of life (QoL) in patients with nonsmall cell lung carcinoma (NSCLC) who fail
      first-line platinum-based regimens. The authors sought to determine the activity
      of second-line, low-dose, weekly paclitaxel in patients with NSCLC who failed
      first-line chemotherapy with carboplatin plus paclitaxel. METHODS: Patients with
      Stage IIIB/IV NSCLC who had received first-line carboplatin/paclitaxel were
      treated with low-dose (80 mg/m(2)), weekly paclitaxel at the time of disease
      progression. Response rates, QoL, and survival were outcome end points. RESULTS:
      Sixty-two patients were included in this analysis. The median age was 62 years
      (range, 32-76 years), 55% of patients were male, 89% of patients had Stage IV
      NSCLC, and the Karnofsky performance status was 90-100% in 31% of patients, 70
      80% in 55% of patients, and 60% in 14% of patients. Twenty-six percent of
      patients experienced disease progression as their best response to first-line
      carboplatin plus paclitaxel, whereas 52% of patients had stable disease, and 23%
      of patients had achieved a response. The median time from first-line carboplatin
      plus paclitaxel to second-line, low-dose, weekly paclitaxel was 9.5 weeks (range,
      1-78 weeks). The toxicity profile was extremely favorable, with no Grade 4
      toxicity and < 10% Grade 3 hematologic or nonhematologic toxicity in all patients
      with the exception of neuropathy. Ten percent of patients experienced both Grade
      2 and Grade 3 neuropathy. The overall objective response rate was 8%. The median
      survival was 5.2 months (95% confidence interval [95%CI], 3.6-6.2 months), and
      the 1-year and 2-year survival rates were 20% (95%CI, 10-30%) and 9% (95%CI, 1
      16%), respectively. CONCLUSIONS: Second-line, low-dose, weekly paclitaxel had
      activity in selected patients with Stage IIIB/IV NSCLC who failed first-line
      chemotherapy with carboplatin plus paclitaxel. The toxicity profile of this
      approach is extremely favorable, and outcome expectations are similar to the
      outcome expectations with other single agents in this setting.

PMID- 12216095
TI  - A Phase II trial of topotecan and gemcitabine in patients with previously
      treated, advanced nonsmall cell lung carcinoma.
AB  - BACKGROUND: Multiple trials have been performed to evaluate second-line clinical
      chemotherapy in patients with advanced nonsmall cell lung carcinoma (NSCLC).
      However, no single agent or combination has demonstrated superior activity.
      METHODS: Patients with advanced NSCLC who had already received one
      chemotherapeutic regimen were treated with topotecan (0.75 mg/m(2) over 30
      minutes, Days 1-5) and gemcitabine (400 mg/m(2) over 30 minutes, Days 1 and 5)
      every 21 days. RESULTS: Of 35 patients who were treated, 4 (11%) achieved a
      partial responses and 8 (23%) hadstable disease for at least four courses of
      treatment. The response rate for patients with refractory disease (progressing
      during frontline chemotherapy) was 18% (3 of 17) with 18% having stable disease
      for at least four courses of treatment. The median survival of the entire group
      was 7 months (range, 1.5-44 months) and 20% (7 of 35) of patients were alive 1
      year from the initiation of topotecan and gemcitabine treatment. Patients with
      refractory disease had a median survival of 4(1/2) months, with 6-month and 1
      year survival rates of 47% and 18%, respectively. During Course 1, five patients
      (14%) developed Grade IV neutropenia and three patients (9%) developed Grade IV
      thrombocytopenia. Nonhematologic toxicity was relatively mild, with one patient
      developing Grade III side effects (fatigue) and eight patients (23%) developing
      Grade II nonhematologic side effects. CONCLUSIONS: The combination of topotecan
      and gemcitabine demonstrated antitumor activity with a modest side effect profile
      in patients with advanced, previously treated NSCLC.

PMID- 12216096
TI  - Prospective randomized study of four novel chemotherapy regimens in patients with
      advanced nonsmall cell lung carcinoma: a minnie pearl cancer research network
      trial.
AB  - BACKGROUND: The authors compared the toxicity, response rate, and progression
      free survival of four chemotherapy regimens for patients with advanced (Stage
      IIIB and IV) nonsmall cell lung carcinoma. METHODS: A total of 267 patients
      entered this randomized Phase II trial on one of four arms: paclitaxel,
      carboplatin, and gemcitabine (Arm A); paclitaxel, carboplatin, and vinorelbine
      (Arm B); paclitaxel and gemcitabine (Arm C); and gemcitabine and vinorelbine (Arm
      D). Patient characteristics were similar in all treatment arms. At the time of
      tumor progression, patients were removed from study and were treated at the
      discretion of their physician. RESULTS: Patients received a median of four
      courses of chemotherapy in all arms, and there was no difference in the dose
      delivered. There were no statistical differences in response rates (range, 32
      45%), median progression free survival (range, 4.9-6.6 months), or progression
      free survival at 1 year (range, 8-19%). Actuarial survival in all four arms was
      not different, with a median survival ranging from 8.7 months to 10.7 months and
      a 1-year survival rate of 38-44%. Each arm was compared with a historic control
      with a median survival of 8 months. Arm D (gemcitabine and vinorelbine)
      approached significance at the 0.05 level. CONCLUSIONS: Two-drug combinations
      containing the newer drugs without a platinum drug were less toxic than three
      drug, platinum-based regimens. There were no significant differences in objective
      response rates or progression free survival when the four regimens were compared.
      The two-drug combination of gemcitabine and vinorelbine was the least toxic and,
      thus, may be superior. A Phase III trial comparing combined gemcitabine and
      vinorelbine with combined paclitaxel, carboplatin, and gemcitabine is ongoing.

PMID- 12216097
TI  - The long-term clinical course of patients with cutaneous melanoma.
AB  - BACKGROUND: The clinical course of cutaneous melanoma is associated with
      pathologic and clinical factors, such as thickness, ulceration, and location of
      tumor and gender of the patient. The authors used a parametric survival model
      that incorporated a cured fraction of patients to translate these factors into
      specific estimates of long-term outcome. METHODS: A cohort study was conducted of
      5837 patients who were treated for localized cutaneous melanoma between 1978 and
      1990 at the Duke Comprehensive Cancer Center. Of these, 495 patients were
      excluded because the survival status or one or more of the prognostic factors was
      unknown. Maximum follow-up was 22 years. The primary outcome measures examined
      were cured fraction (probability of cure), median tumor specific survival (i.e.,
      median time to death from tumor), and the probability of tumor-related survival
      at fixed intervals after treatment. RESULTS: For an example of a class of
      patients with a relatively good prognosis, consider women with nonulcerated
      lesions measuring 0.5 mm thick on an extremity. The probability of cure (+/-
      standard error) for these patients was estimated at 80.8% +/- 2.0%, and the
      median tumor specific survival was 10.0 years +/- 0.8 years. This suggests that,
      in these patients, half of the deaths from melanoma will occur more than 10 years
      after treatment, barring death from other causes. Conversely, men with ulcerated
      lesions measuring 8.00 mm thick on the trunk have a relatively poor prognosis.
      The probability of cure for these patients was 16.8% +/- 2.4%, and the median
      tumor specific survival was 2.7 years +/- 0.2 years. Despite this poor initial
      prognosis, the conditional probability of cure increased to 90%; after 15 years
      of recurrence free survival. CONCLUSIONS: Parametric statistical analysis
      provides quantitative measures of long-term survival. These measures show that
      late recurrence-longer than a decade after treatment-is to be expected in a
      significant portion of patients, although the probability of cure increases with
      progressively longer recurrence free survival.

PMID- 12216098
TI  - Phase I study of fotemustine in pediatric patients with refractory brain tumors.
AB  - BACKGROUND: Fotemustine is a nitrosourea with theoretic and preclinical
      advantages over the original analogs, carmustine and lomustine, in the treatment
      of brain tumors. This is the first pediatric Phase I study of fotemustine.
      METHODS: Patients younger than 21 with recurrent/resistant brain tumors were
      enrolled in a conventional Phase I study. Fotemustine was administered
      intravenously every 3 weeks at increasing dose levels starting at 100 mg/m(2).
      Toxicity and response data were monitored closely. RESULTS: Fifteen evaluable
      patients entered the study and received a total of 45 courses of fotemustine
      (dose range, 100-175 mg/m(2)). Myelosuppression was observed, with the dose
      limiting toxicity being Grade 4 neutropenia and thrombocytopenia. Toxicity was
      delayed and cumulative. The maximum tolerated dose was 150 mg/m(2) every 3 weeks.
      There were three documented radiologic responses (20% of patients) comprising one
      partial response and two minor responses in patients with a sarcoma,
      medulloblastoma, and ependymoma, respectively. CONCLUSIONS: Fotemustine
      administered at a dose of 150 mg/m(2) every 3 weeks is well tolerated in children
      and has antitumor activity in several brain tumors. This is the first dedicated
      Phase I study of a single agent nitrosourea in a pediatric population. More
      comparative studies should be undertaken to define the optimum nitrosourea analog
      for use in children with brain tumors.

PMID- 12216099
TI  - Clinical and survival covariates of eight classes of childhood supratentorial
      neuroglial tumors.
AB  - BACKGROUND: In the current study, the authors investigated clinical, surgical,
      and histologic characteristics (covariates) and their interactions in eight
      previously identified classes of childhood supratentorial neuroglial tumors. The
      classes resulted from 5 factor score profiles on 703 supratentorial neuroglial
      tumors in the Childhood Brain Tumor Consortium database. METHODS: The Cox
      proportional models were used to identify class survival covariates. RESULTS: Age
      was found to be a survival covariate only in Class 1, in which older age
      increased the 5-year survival rate 73% from the first year (0.49) to the tenth
      year (0.85). A greater amount of tumor removed improved survival in Classes 2 and
      4 only. Rosenthal fibers improved survival in Class 2 and overrode the negative
      effects of high Proliferative factor scores and pleomorphic nuclei. Survival for
      Class 3 children with high Proliferative factor scores improved from 0.60 to 0.95
      as the Spongy factor scores increased. Survival in Class 4 increased from 0.17 to
      0.39 with total tumor removal. Irregular nuclei and glomeruloid capillaries
      improved survival in Class 5 patients. Class 6 survival improved with low cell
      density. Macrocysts in tumors in Classes 1 and 5 were found to improve survival.
      CONCLUSIONS: As a result of the current study, the authors conclude that survival
      covariates differ with tumor class and may modify prognosis considerably.

PMID- 12216100
TI  - Pretreatment cognitive performance predicts survival in patients with
      leptomeningeal disease.
AB  - BACKGROUND: Leptomeningeal disease (LMD) involves the spread of malignant cells
      from solid tumors to the cerebrospinal fluid or to the leptomeninges. LMD has a
      very poor prognosis and it is difficult to diagnose and follow with traditional
      diagnostic tools. The purposes of this study were to characterize cognitive
      functioning of LMD patients before treatment and to determine if measurement of
      cognitive functioning could be used to predict survival time. METHODS: Thirty
      seven subjects with LMD were administered the Mattis Dementia Rating Scale (DRS)
      before they received treatment and statistical analyses were performed. RESULTS:
      The Conceptualization subtest of the DRS was the most sensitive to disease
      course. It was the only individual subtest to predict survival and it was the
      most impaired subtest across individual subjects. These results support earlier
      findings of a frontal-subcortical pattern of dysfunction in LMD patients.
      Cognitive performance at time of LMD diagnosis predicts survival time. Age and
      clinical status, two factors often correlated with survival in the cancer
      literature, did not predict survival time for our LMD population. In addition,
      there were no correlations between survival time and previous medical history or
      demographic factors. CONCLUSIONS: Neuropsychological assessment appears to be a
      valuable tool both for tracking disease course over time and for predicting
      survival of patients.

PMID- 12216101
TI  - Long-term follow-up of patients with giant cell tumor of the sacrum treated with
      selective arterial embolization.
AB  - BACKGROUND: Giant cell tumors of the bone can behave as aggressive and sometimes
      lethal tumors. In the sacrum, the tumor can be extremely difficult to manage.
      Standard treatments, including surgery and radiation, are associated with
      significant complications and recurrence rates. The goal of this study is to
      evaluate the long-term outcome of selective arterial embolization as an
      alternative treatment modality. METHODS: From 1975 to 2001, 18 patients were
      treated with selective intraarterial embolization. The embolization method was a
      combination of Gelfoam particles and coils for peripheral and central occlusions,
      respectively. The number of embolizations was based on clinical symptoms,
      radiographic response, and the vascularity of the tumor. Nine patients received
      intraarterial cisplatin as part of their treatment. The median follow-up was 105
      months. RESULTS: Of 18 patients, 14 responded favorably to embolization with
      improvement in pain and neurologic symptoms. Computed tomographic and magnetic
      resonance imaging scans showed reossification and stabilization of tumor size.
      Arteriograms showed diminished vascularity. With long-term follow-up, three
      patients developed late disease recurrences within the sacrum. Kaplan-Meier
      analysis showed that the risk of local recurrence is 31% at 10 years and 43% at
      15 and 20 years. The long-term outcome was not affected by intraarterial
      cisplatin. There was one death that occurred 1 day after embolization.
      CONCLUSIONS: Most patients demonstrate an objective early radiographic response
      to embolization. Long-term follow-up shows that the response is durable in
      approximately one half of the patients. Given the potential morbidity of other
      treatments, embolization should be included in the armamentarium of treatment for
      this difficult disease. Embolization may be used alone or in conjunction with
      other therapy. Long-term follow-up is recommended for all patients because late
      disease recurrence or sarcomatous change can occur.

PMID- 12216102
TI  - Nonneutropenic febrile episodes associated with docetaxel-based chemotherapy in
      patients with solid tumors.
AB  - BACKGROUND: Docetaxel is associated with severe lymphopenia and increased
      incidence of nonneutropenic infection. This study investigated the incidence of
      nonneutropenic infections and/or febrile episodes in patients with solid tumors
      receiving frontline docetaxel-based chemotherapy. METHODS: Chemotherapy-naive
      patients with solid tumors treated with docetaxel-based chemotherapy were studied
      prospectively for the development of nonneutropenic infections. RESULTS: During a
      2-year period, 680 cancer patients enrolled in 24 protocols received 2867 cycles
      of docetaxel-containing chemotherapy. Fifty-three patients (7.8%) developed
      nonneutropenic infections and/or febrile episodes. The most common of these were
      pulmonary infections (n = 25), Pneumocystis carinii interstitial pneumonias (n =
      5), and candidal (n =11), herpetic (n =4), and cytomegaloviral (n =3) infections.
      Thirty-six patients (68%) had severe lymphopenia (< 900 cells per deciliter) and
      49 (92%) had less than 400 CD4(+) cells per deciliter. Patients with a low CD4(+)
      cell count (</= 200 cells per deciliter) had a significantly higher probability
      to develop opportunistic than common infections (P = 0.002). The incidence of
      nonneutropenic infections and/or febrile episodes was significantly higher in
      patients treated with docetaxel/gemcitabine (18.3%; P = 0.0001) and
      docetaxel/CDDP (11.7%; P = 0.012) than in those treated with docetaxel alone
      (3.6%). Conversely, 175 patients who received 752 cycles of chemotherapy with
      paclitaxel-containing regimens and 410 patients who received 2174 cycles with
      nontaxane-based regimens developed 6 (3.4%; p=0.042) and 12 (3%; p=0.001)
      nonneutropenic infections, respectively. Less than 10% of the patients of the two
      latter groups were lymphopenic. The risk of nonneutropenic infection in patients
      receiving docetaxel-based chemotherapy was 2.38 and 2.8 times higher than in
      patients receiving paclitaxel and nontaxane-based chemotherapy, respectively.
      CONCLUSIONS: Patients treated with docetaxel-based chemotherapy are at increased
      risk of developing nonneutropenic infections. This may be related, at least
      partly, to severe postchemotherapy CD4(+) lymphopenia.

PMID- 12216103
TI  - Magnetic resonance imaging as a supplement for the clinical staging system of
      Durie and Salmon?
AB  - BACKGROUND: This study evaluated the prognostic value of a three-grade staging
      system of spinal involvement using magnetic resonance imaging (MRI) in patients
      with multiple myeloma and determined its usefulness as an independent parameter
      in the staging system of Durie and Salmon. METHODS: Seventy-seven previously
      untreated patients with multiple myeloma underwent MRI of the thoracic and lumbar
      spine with unenhanced T1-weighted spin echo and short-tau inversion time
      inversion recovery sequences. The patients were evaluated according to their
      infiltration patterns and the extent of bone marrow involvement was staged using
      a three-grade scale: Stage I, no focal or diffuse infiltration; Stage II, 1-10
      foci or mild diffuse infiltration; Stage III, more than 10 foci or strong diffuse
      infiltration. RESULTS: The infiltration patterns had no significant effect on
      survival. Of 77 patients, 25 would have been understaged using the standard
      staging system of Durie and Salmon without the findings of MRI and 8 patients
      would have been understaged if the staging was based only on MRI. The combination
      of the staging system of Durie and Salmon and MRI was highly significant with
      respect to survival (P < 0.0001, log rank analysis). MRI staging I-III was
      independent of the staging system of Durie and Salmon (Cox regression model).
      CONCLUSIONS: A three-grade staging of spinal MRI provides a significant
      prognostic tool for patients with multiple myeloma. The authors propose including
      it in the staging system of Durie and Salmon.

PMID- 12216104
TI  - Age specific and attributable risks of familial prostate carcinoma from the
      family-cancer database.
AB  - BACKGROUND: Familial risks by proband status and age are useful for clinical
      counseling, and they can be used to calculate population-attributable fractions
      (PAFs), which show the proportion of disease that could be prevented if the cause
      could be removed. METHODS: The authors used the nationwide Swedish Family-Cancer
      Database on 10.2 million individuals and 182,104 fathers and 3710 sons with
      medically verified prostate carcinoma to calculate age specific familial
      standardized incidence ratios (SIRs) with 95% confidence intervals (95%CI) and
      familial PAFs for prostate carcinoma in sons ages 0-66 years. RESULTS: The
      incidence of prostate carcinoma was doubled between the years 1961 and 1998. The
      familial SIRs for prostate carcinoma were 2.38 (95%CI, 2.18-2.59) for men with
      prostate carcinoma in the father only, 3.75 (95%CI, 2.73-4.95) for men with
      prostate carcinoma in a brother only, and 9.44 (95%CI, 5.76-14.03) for men with
      prostate carcinoma in both a father and a brother. The corresponding familial
      PAFs were 8.86%, 1.78%, and 0.99%, respectively, yielding a total PAF of 11.63%.
      Age specific risks were shown for the same proband histories. The SIR was 8.05
      for prostate carcinoma before age 55 if a brother had been diagnosed before that
      age. If, in addition, a father was diagnosed at any age, then the SIR was 33.09.
      CONCLUSIONS: The authors recommend that having a brother who is diagnosed with
      prostate carcinoma before age 55 years or having a brother and father who are
      diagnosed at any age are indications to screen for prostate carcinoma. The
      familial PAF of prostate carcinoma among a population of sons ages 0-66 years was
      11.63%.

PMID- 12216105
TI  - Peripheral blood stem cell support reduces the toxicity of intensive chemotherapy
      for children and adolescents with metastatic sarcomas.
AB  - BACKGROUND: To increase the dose intensity (DI) of chemotherapy for pediatric
      patients with metastatic sarcomas, including the Ewing sarcoma family of tumors
      (ESFT) and rhabdomyosarcoma (RMS), the authors tested the feasibility of an
      intensive regimen supported by granulocyte-colony stimulating factor (G-CSF) and
      peripheral blood stem cells (PBSC). METHODS: Twenty-three children and
      adolescents with metastatic sarcomas received vincristine, doxorubicin,
      cyclophosphamide, ifosfamide, sodium mercaptoethanesulfonate (mensa), and
      etoposide (VACIME) chemotherapy, consisting of 8 courses of vincristine 2 mg/m(2)
      on Day 0, doxorubicin 37.5 mg/m(2) per day on Days 0-1, cyclophosphamide 360
      mg/m(2) per day on Days 0-4, ifosfamide 1800 mg/m(2) per day on Days 0-4, mesna
      2400 mg/m(2) per day, and etoposide 100 mg/m(2) per day on Days 0-4. Doxorubicin
      was omitted in Courses 7 and 8. G-CSF was given after each course of therapy.
      Courses of therapy were repeated every 21 days or as soon as hematopoietic
      recovery permitted. PBSC were collected twice: first, after Course 2 (infused
      after Courses 3 and 4) and, second, after Course 4 (infused after Courses 5 and
      6). Surgical resection followed Course 6, and radiotherapy followed Course 8.
      RESULTS: PBSC collections were adequate in 91% of all harvests. The mean DI was
      82% (standard deviation, 14%) of the intended DI, which was greater than historic
      data without PBSC support. Seventeen patients (74%) achieved a complete response
      (CR), 12 patients with chemotherapy alone and 5 more patients after undergoing
      surgical resection. Fifteen patients developed progressive disease, with a 2-year
      event free survival (EFS) rate of 39% (95% confidence interval, 19-59%).
      Hematopoietic toxicity was severe and cumulative, although it was less than that
      seen previously without PBSC support. CONCLUSIONS: PBSC-supported multicycle
      chemotherapy is a feasible method to increase chemotherapy DI for pediatric
      patients with metastatic sarcomas. Although the CR rate compared favorably with
      previously reported response rates, the 2-year EFS rate was similar to that
      achieved with other intensive regimens.

PMID- 12216106
TI  - Chronic neuroblastoma.
AB  - BACKGROUND: An indolent course is associated with neuroblastoma (NB) in
      adolescents and adults. In the current study, the authors analyzed this
      phenomenon in a large series of children with metastatic NB. METHODS: The authors
      studied 38 patients who were diagnosed with NB in the first decade of life and
      had metastatic disease 5 years or more from diagnosis. RESULTS: The median age at
      diagnosis was 3 years 10 months. MYCN was amplified in 2 of 28 patients tested.
      Of 30 patients with classic Stage 4 NB, 9 had a late first recurrence of disease
      (4.3-13 years from diagnosis). Of eight patients who had atypical cases at
      diagnosis (one isolated mandibular lesion, two Stage 4-N, five non-Stage 4), six
      had a late first distant recurrence of disease (4 years 11 months-38 years 8
      months). Nineteen patients were off therapy continuously for 3 years or more
      before disease recurred a first or second time. Myeloablative therapy was used to
      consolidate a first or second response in 27 patients. High-dose conventional
      therapy helped to achieve a second remission of disease in 9 of 20 patients
      assessable for response of first recurrence but achieved no major responses of
      second or third relapse in 10 of 11 patients. The combination of anti-G(D2)
      immunotherapy and/or cis-retinoic acid, targeted radiotherapy, and multiple
      cycles of chemotherapy with modest toxicity helped prolong survival. Twelve
      patients survive at 5 years 6 months+ to 19 years 4 months+ from diagnosis
      (median, 6 years 10 months+), including four with complete remission of disease;
      10 received anti-G(D2) immunotherapy after recurrence. The other 26 patients died
      of disease (n = 22) or toxicity (n = 4) at 5 years-41 years 5 months from
      diagnosis (median, 6 years 5 months). CONCLUSIONS: The concept of indolent or
      smoldering NB should not be limited to adolescents/adults. The expanding
      repertoire of anti-NB treatments, including biologic therapies and chemotherapy
      regimens of modest toxicity, can convert childhood NB into a chronic disease with
      prolonged survival after recurrence.

PMID- 12216107
TI  - Metabolic characterization of childhood brain tumors: comparison of 18F
      fluorodeoxyglucose and 11C-methionine positron emission tomography.
AB  - BACKGROUND: Positron emission tomography (PET) scans of primary brain tumors were
      performed in pediatric patients to examine whether metabolic characteristics
      could be used as an index of clinical aggressiveness. METHODS: Twenty-seven
      pediatric patients with untreated primary central nervous system neoplasms were
      studied with PET scans using 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG) and/or L
      [methyl-(11)C] methionine (MET). Metabolic characteristics as assessed with FDG
      and MET standardized uptake values (SUV) and SUV-to-normal brain ratios were
      compared with histopathology and selected histochemical features such as
      proliferation activity (Ki-67(MIB-1)) and apoptotic, vascular, and cell density
      indices. The median followup time was 43 months. RESULTS: The accumulation of
      both FDG and MET was significantly higher in high-grade than in low-grade tumors,
      but a considerable overlap was found. The accumulation of both tracers was
      associated positively with age. High-grade tumors showed higher proliferative
      activity and vascularity than the low-grade tumors. In univariate analysis, FDG
      PET, MET-PET, and apoptotic index were independent predictors of event-free
      survival. CONCLUSION: We found that both FDG and MET uptake in pediatric brain
      tumors are associated with malignancy grade. However, no clear limits of SUVs and
      SUV-to-normal brain ratios can be set between low-grade and high-grade tumors,
      which makes the assessment of malignancy grade using metabolic imaging with PET
      scan difficult in individual cases. Although FDG-PET and MET-PET do not
      compensate for histopathologic evaluation, they may give valuable additional
      information especially if invasive procedures to obtain histopathologic samples
      are not feasible.

PMID- 12216108
TI  - The signaling adapter protein PINCH is up-regulated in the stroma of common
      cancers, notably at invasive edges.
AB  - BACKGROUND: PINCH is an LIM (double zinc finger domain) protein that functions as
      an adapter at a key convergence point for integrin and growth factor signal
      transduction. Because no information is available regarding its expression in
      vivo in human tissues, this study evaluated the distribution and abundance of
      PINCH in patients with breast, prostate, lung, colon, and skin carcinomas.
      METHODS: A polyclonal antibody was raised to a purified 6-histidine PINCH fusion
      protein and used to evaluate 74 cases comprising 33 breast carcinomas (21 ductal
      carcinomas, 6 lobular carcinomas, 4 ductal carcinomas in situ, 2 lobular
      carcinomas in situ), 22 prostate carcinomas, 5 colon carcinomas, 6 lung
      carcinomas (3 adenocarcinomas and 3 squamous carcinomas), and 8 skin carcinomas
      (4 basal cell carcinomas and 4 squamous cell carcinomas) by immunoperoxidase
      histochemistry of formalin-fixed, paraffin-embedded tissues. Lysates of frozen
      tissue from the epithelium of two normal breasts and six breast carcinomas were
      evaluated by immunoblotting. RESULTS: Immunostaining for PINCH was increased in
      the cytoplasm of fibroblastoid cells in areas of the tumor-associated stroma in
      all carcinomatous tissues evaluated. The most intense stromal immunostaining for
      PINCH was noted at invasive edges, particularly in breast carcinomatous tissue.
      Immunoblotting of lysates from normal breast and breast carcinomatous tissue
      confirmed that PINCH protein expression was markedly increased in breast
      carcinomatous tissues. CONCLUSIONS: PINCH is up-regulated in tumor-associated
      stromal cells, particularly at invasive edges, and may be a marker for stroma
      manifesting the ability to facilitate invasion. Because of this and because PINCH
      functions as a "molecular switch" in signal transduction, PINCH may be a new
      target for drug discovery aimed at the tumor-associated stroma.

PMID- 12216109
TI  - Functional involvement of src and focal adhesion kinase in a CD99 splice variant
      induced motility of human breast cancer cells.
AB  - Earlier report showed that expression of a splice variant of CD99 transmembrane
      protein increases invasive ability of human breast cancer cells. Cell motility
      was also significantly enhanced by the CD99 splice variant expression. In an
      effort to identify the cellular components that mediate a signal transduction
      pathway triggered by the CD99 splice variant, known signal path inhibitors were
      examined for their effects on the motility of the CD99 splice variant-transfected
      MDA-MB-231 breast cancer cells. Phenylarsine oxide, an inhibitor of phosphatase
      specific for focal adhesion kinase, and PP1, an inhibitor of src kinase family,
      significantly suppressed motility of the cells. Among different types of src
      transfectant clones generated, kinase-negative mutant src transfectant cells were
      80% less motile than the mock cells transfected with an empty-vector, while v-src
      and c-src transfectants exhibited cell motility levels at or slightly above the
      mock transfectant. These results suggest that src and focal adhesion kinase
      mediate the intracellular signaling pathway of a CD99 splice variant for the
      induction of motility of human breast cancer cells.

PMID- 12216110
TI  - Genome-wide expression profiling of 8-chloroadenosine- and 8-chloro-cAMP-treated
      human neuroblastoma cells using radioactive human cDNA microarray.
AB  - Previous reports raised question as to whether 8-chloro-cyclic adenosine 3,5
      monophosphate (8-Cl-cAMP) is a prodrug for its metabolite, 8-Cl-adenosine which
      exerts growth inhibition in a broad spectrum of cancer cells. The present study
      was carried out to clarify overall cellular affects of 8-Cl-cAMP and 8-Cl
      adenosine on SK-N-DZ human neuroblastoma cells by systematically characterizing
      gene expression using radioactive human cDNA microarray. Microarray was prepared
      with PCR-amplified cDNA of 2,304 known genes spotted on nylon membranes,
      employing (33)P-labeled cDNAs of SK-N-DZ cells as a probe. The expression levels
      of approximately 100 cDNAs, representing about 8% of the total DNA elements on
      the array, were altered in 8-Cl-adenosine- or 8-Cl-cAMP-treated cells,
      respectively. The genome-wide expression of the two samples exhibited partial
      overlaps; different sets of up-regulated genes but the same set of down-regulated
      genes. 8-Cl-adenosine treatment up-regulated genes involved in differentiation
      and development (LIM protein, connexin 26, neogenin, neurofilament triplet L
      protein and p21(WAF1/CIP1)) and immune response such as natural killer cells
      protein 4, and down-regulated ones involved in proliferation and transformation
      (transforming growth factor-beta, DYRK2, urokinase-type plasminogen activator and
      proteins involved in transcription and translation) which were in close parallel
      with those by 8-Cl-cAMP. Our results indicated that the two drugs shared common
      genomic pathways for the down-regulation of certain genes, but used distinct
      pathways for the up-regulation of different gene clusters. Based on the findings,
      we suggest that the anti-cancer activity of 8-Cl-cAMP results at least in part
      through 8-Cl-adenosine. Thus, the systematic use of DNA arrays can provide
      insight into the dynamic cellular pathways involved in anticancer activities of
      chemotherapeutics.

PMID- 12216111
TI  - The characteristics of integrins expression in decidualized human endometrial
      stromal cell induced by 8-Br-cAMP in in vitro.
AB  - Integrins are heterodimeric glycoproteins that have been found to undergo dynamic
      temporal and spatial changes in the endometrium during the menstrual cycle and in
      early pregnancy. Specificity of integrins is known to be different in human
      endometrial stromal cells and decidual cells. These shifts of integrins suggested
      to play an important role in embryo implantation and can be modulated by
      progesterone, cAMP derivatives, and cytokines. The mechanisms of decidualization
      and its precise physiological role are still not clearly understood and in vitro
      systems could provide an alternative that overcomes limitations of studying such
      complex biological phenomena in vivo at the time of implantation. This study was
      undertaken to establish an in vitro model system for human decidualization using
      8-bromo-cAMP and to investigate the characteristics of stromal integrin
      expression in vitro by 8-Br-cAMP. Endometrial stromal cells were isolated and
      cultured, and then were induced to decidualize by 0.5 mM 8-Br-cAMP for 15 days.
      Immunofluorescence staining and flow cytometric analyses of the integrin subunits
      (alpha1, alpha4, alpha5, alpha6, beta1 and alphavbeta3) were performed at day 9.
      In the presence of 8-Br-cAMP, the staining intensity of alphavbeta3 was
      significantly higher than control and measurements for alpha1, alpha4, alpha5,
      alpha6, and beta1 were similar. Immunofluorescent localization of the integrins
      reflected the differences obtained from the flow cytometric analyses described
      above. In summary, the expression of alphavbeta3 integrin increased in stromal
      cells in vitro decidualized by 8-Br-cAMP and this up-regulation of alphavbeta3
      integrin expression during decidualization might influence on human implantation.

PMID- 12216112
TI  - Differential effects of Fas cross-linking on phospholipase D activation and
      related lipid metabolism in Fas-resistant A20 cells.
AB  - A20 murine lymphoma cells undergoing Fas-mediated apoptosis showed increase in
      the activity of phospholipase D (PLD), which is involved in proliferative or
      mitogenic cellular responses. Using A20 cell lines that were resistant to Fas
      induced apoptosis, we investigated the differential effects of Fas cross-linking
      on PLD activity and sphingolipid metabolism. The basal PLD activities in all of
      the selected three Fas-resistant clones (#5, #8, and #11) were about 2~4 folds
      higher than that of wild type A20 cells. Among the PLD isoforms, PLD2 expression
      was increased in all of the selected Fas-resistant clones. The Fas downstream
      signaling events triggered by Fas cross-linking, including the activations of
      PLD, phosphatidylcholine-specific phospholipase C (PC-PLC), sphingomyelinase
      (SMase), the increase in diacylglycerol (DAG) and protein phosphorylation levels,
      and the translocation of protein kinase C to membrane were not changed in both of
      Fas-resistant clone #5 and #8. In contrast, Fas cross-linking stimulated the
      activity of PLD, PC-PLC, and SMase, translocation of PKC, and protein
      phosphorylation in Fas-resistant clone #11, similar to that of wild type cells.
      We also found that clone #11 had a different Fas sequence encoding Fas B which
      has been known to inhibit Fas-induced apoptosis. These findings suggest that
      increased PLD2 expression resulting in increased basal PLD activity and the
      blockade of Fas downstream signaling cascades may be involved to limit apoptosis
      induced by Fas cross-linking.

PMID- 12216114
TI  - Effect of local background intensities in the normalization of cDNA microarray
      data with a skewed expression profiles.
AB  - Normalization of the data of cDNA microarray is an obligatory step during
      microarray experiments due to the relatively frequent non-specific errors.
      Generally, normalization of microarray data is based on the null hypothesis and
      variance model. In the Yang's model (Yang et al., 2001), at least two types of
      noises are included. The one is additive noise and the other is multiplicative
      noise. Usually, background is considered as one of additive noise to the signal
      and the variation between the signal pixels is the representative multiplicative
      noise. In this study, the relation between the signal (spot intensity minus
      background intensity) and background was observed and the influence of background
      on normalization as a representative additive factor was investigated. Although
      the relation has not been considered as a factor affecting the normalization, it
      could improve the accuracy of microarray data when the normalization was carried
      out considering signal/background ratio. The background dependent normalization
      decreased the number of genes whose expression levels were changed significantly
      and it could make their distribution more consistent through the whole range of
      signal intensities. In this study, printing pin dependent normalization was also
      carried out regarding the printing pin as a representative multiplicative noise.
      It improved the distribution of spots in the Cy3-Cy5 scatter plot, but its effect
      was slight. These studies suggest that there are some influences of the signals
      on the local backgrounds and they must be considered for the normalization of
      cDNA microarray data.

PMID- 12216113
TI  - Structural basis for inhibition of protein tyrosine phosphatases by Keggin
      compounds phosphomolybdate and phosphotungstate.
AB  - Protein-tyrosine phosphatases (PTPs) constitute a family of receptor-like, and
      cytoplasmic enzymes, which catalyze the dephosphorylation of phosphotyrosine
      residues in a variety of receptors and signaling molecules. Together with protein
      tyrosine kinases (PTKs), PTPs are critically involved in regulating many cellular
      signaling processes. In this study, diverse compounds were screened for PTP
      inhibition and selectively screened for inhibitors with the end product
      inhibition properties. Among phosphate analogues and their derivatives for PTP
      inhibition, Keggin compounds phosphomolybdate (PM) and phosphotungstate (PT)
      strongly inhibited both PTP-1B and SHP-1, with K(i) values of 0.06-1.2 micromM in
      the presence of EDTA. Unlike the vanadium compounds, inhibition potencies of PM
      and PT were not significantly affected by EDTA. PM and PT were potent,
      competitive inhibitors for PTPs, but relatively poor inhibitors of Ser/Thr
      phosphatase. Interestingly, PM and PT did not inhibit alkaline phosphatase at
      all. The crystal structure of PTP-1B in complex with PM, at 2.0 A resolution,
      reveals that MoO(3), derived from PM by hydrolysis, binds at the active site. The
      molybdenium atom of the inhibitor is coordinated with six ligands: three oxo
      ligands, two apical water molecules and a S atom of the catalytic cysteine
      residue. In support of the crystallographic finding, we observed that molybdenium
      oxides (MoO(3), MoO(2), and MoO(2)Cl(2)) inhibited PTP-1B with IC(50) in the
      range 5-15 micromM.

PMID- 12216115
TI  - Expression and characterization of a mutant recombinant blood coagulation factor
      VIII (rFVIII (m)).
AB  - In an earlier study, a site directed mutant rFVIII (rFVIII(m), Arg(336) -->
      Gln(336)) expressed in baculovirus-insect cell (Sf9) system was found to sustain
      high level activity during incubation at 37 degrees celsius for 24 h while the
      cofactor activity of normal plasma was declined steadily. In this study, a mutant
      B-domain deleted rFVIII(m), Arg(336) --> Gln(336) expressed in baculovirus-insect
      cell (Sf9) system was characterized for its enzymatic and chemical properties.
      The expressed rFVIII(m) and plasma FVIII (pFVIII) were purified by immunoaffinity
      column chromatography and identified by Western blot analysis. The partially
      purified rFVIII(m) exhibited cofactor specific activity of 2.01 x 10(3)units/mg
      protein. The molecular weight of rFVIII(m) ranged between 40 to 150 kDa with a
      major band at 150 kDa. Treatment of both rFVIII(m) and pFVIII with thrombin
      increased their cofactor activity in a similar pattern. Treatment of both the
      activated rFVIII(m) and native FVIII with APC decreased their cofactor
      activities, however, the former exhibited a slower decrease than the latter,
      although no significant difference was present. rFVIII(m) formed a complex with
      vWF, resulting in a stabilized form, and the lag period of thrombin-mediated
      activating was extended by vWF association. These results implicated that
      rFVIII(m) expressed in baculovirus-insect cell system had a comparable capacity
      as FVIII cofactor activity and might be a good candidate for the FVIII
      replacement therapy for hemophilia A patients.

PMID- 12216116
TI  - Cholesterol induce oligomerization of Vibrio vulnificus cytolysin specifically.
AB  - Vibrio vulnificus cytolysin (VVC) has been implicated as one of the important
      virulence determinants of V. vulnificus that causes serious septicemia and wound
      infection. An attempt was made to investigate that VVC could act as a ligand
      which stimulates intracellular signaling systems. Cholesterol dose-dependently
      blocked VVC hemolytic activity through oli-gomerization of cytolysin. Among
      cholesterol derivatives including 7-dehydrocholesterol, cholesteryl esters,
      deoxycholate, and cholestane tested, only 7-dehydrocholesterol induced
      oligomerization as well as inactivation of VVC. These results show that
      oligomerization of VVC is completely dependent on three-dimensional structure of
      cholesterol where specific interaction of cholesterol at oligomerization sites of
      VVC is very selective. These findings support the idea that cholesterol which
      constitute many of cellular plasma membrane could be a receptor of VVC on plasma
      membrane of target cells.

PMID- 12216117
TI  - Sox-4 is a positive regulator of Hep3B and HepG2 cells' apoptosis induced by
      prostaglandin (PG)A(2) and delta(12)-PGJ(2).
AB  - We reported earlier that expression of Sox-4 was found to be elevated during
      prostaglandin (PG) A(2) and delta(12)-PGJ(2) induced apoptosis in human
      hepatocarcinoma Hep3B cells. In this study, the role of Sox-4 was examined using
      human Hep3B and HepG2 cell lines. Sox-4 induction by several apoptotic inducer
      such as A23187 (Ca(2+) ionophore) and etoposide (topoisomerase II inhibitor) and
      Sox-4 transfection into the cells were able to induce apoptosis as observed by
      the cellular DNA fragmentation. Antisense oligonucleotide of Sox-4 inhibited the
      induction of Sox-4 expression and blocked the formation of DNA fragmentation by
      PGA(2) and delta(12)-PGJ(2) in Hep3B and HepG2 cells. Sox-4-induced apoptosis was
      accompanied with caspase-1 activation indicating that caspase cascade was
      involved in this apoptotic pathway. These results indicate that Sox-4 is involved
      in Hep3B and HepG2 cells apoptosis as an important apoptotic mediator.

PMID- 12216119
TI  - [Postradiation intestinal phlegmon].

PMID- 12216118
TI  - Role of Ca(2+) in diallyl disulfide-induced apoptotic cell death of HCT-15 cells.
AB  - Diallyl disulfide (DADS) induced apoptosis through the caspase-3 dependent
      pathway in leukemia cells was earlier reported from this laboratory. In this
      study, we investigated the involvement of Ca(2+) in DADS-induced apoptotic cell
      death of HCT-15, human colon cancer cell line. DADS induced the elevation of
      cytosolic Ca(2+) by biphasic pattern; rapid Ca(2+) peak at 3 min and following
      slow and sustained elevation till 3 h after the addition of DADS. Production of
      H(2)O(2) was also observed with its peak value at 4 h. Apoptotic pathways
      including the sequence of caspase-3 activation, poly(ADP-ribose) polymerase
      cleavage, and DNA fragmentation by DADS were completely blocked by various
      inhibitors such as specific caspase-3 inhibitor, free radical scavenger, and
      intracellular Ca(2+) chelator. N-acetylcystein and catalase treatment prevented
      the accumulation of H2O2 and later caspase-3 dependent apoptotic pathway.
      However, these radical scavengers did not block the elevation of intracellular
      Ca(2+). Treatment of cells with 1, 2-bis (2-aminophenoxyethane)-N, N, N
      tetraacetic acid tetrakis -acetoxymethyl ester (BAPTA-AM), cellular Ca(2+)
      chelator, resulted in a complete blockage of the caspase-3 dependent apoptotic
      pathway of HCT-15 cells. It abolished the elevation of intracellular Ca(2+), and
      furthermore, completely inhibited the production of H(2)O(2). These results
      indicate that cytosolic Ca(2+) elevation is an earlier signaling event in
      apoptosis of HCT-15 cells. Collectively, our data demonstrate that DADS can
      induce apoptosis in HCT-15 cells through the sequential mechanism of Ca(2+)
      homeostasis disruption, accumulation of H(2)O(2), and resulting caspase-3
      activation.

PMID- 12216120
TI  - [Rectal cancer complicated by profuse hemorrhage].

PMID- 12216121
TI  - [Staged correction of surgical pathology of the stomach ("Damage Control") in
      conditions of decompensated hypovolemic shock].
AB  - Based on an analysis of results of treatment of 184 patients the authors make a
      conclusion that staged surgical correction is an expedient method for traumas of
      the abdomen and acute intestinal obstruction with necrosis of the bowel.

PMID- 12216122
TI  - [Immunologic disorders in patients during surgical treatment of ischemic heart
      disease].

PMID- 12216123
TI  - [Antibiotics in bile duct surgery].

PMID- 12216124
TI  - [Contemporary problems in treating rectal cancer. Part II].

PMID- 12216125
TI  - [Features of angioplasty and stenting in atherosclerotic stenting of coronary
      artery occlusions].
AB  - The authors analyze results of coronary angioplasty in 257 patients with ischemic
      heart disease who had occlusions of the coronary arteries. Clinical, angiographic
      and other findings showing the duration of having the occlusions of the coronary
      artery are described in detail. The details of the steps of the technique of the
      endovascular intervention are considered including the most difficult step-
      passing through the occluded portion of the artery. Great attention is given by
      the authors to the criteria of using the correct instruments (conducting
      catheter, conductors, balloon-catheters) during the operation. Good results were
      obtained in 80.2% of the patients after coronary angioplasty. Stenting of the
      coronary arteries was performed in 65 patients (25.3%).

PMID- 12216126
TI  - [Results of surgical treatment of locally-disseminated non-small cell lung
      cancer].
AB  - An analysis of results of operative treatment of 390 patients in 1980-1999 has
      shown growth of incidence of adenocarcinomas, less frequency of exploratory
      thoracotomies and non-radical resections of the lung, postoperative complications
      and lethality, more cases of 5-year survival. Reliable factors of prognosis of
      long-term results of treatment are established.

PMID- 12216127
TI  - [Treatment of acute ulcerations of the upper part of the gastrointestinal tract
      in patient with a neuroreanimation profile].
AB  - A success in treatment of acute ulcerations of the upper parts of the
      gastrointestinal tract in patients with a severe neurosurgical pathology can be
      achieved only with a complex approach to treatment of the intensive care
      patients. The application of antiulcerous medicines in combination with
      pyrokinetics and medicines improving the regeneratory ability of the
      gastrointestinal tract mucosa allowed to considerably decrease risk of the
      development of gastroduodenal bleedings against the background of erosive
      ulcerous lesion of the mucosa. The endoscopic methods of arresting bleedings in
      such patients in combination with the correction of homeostasis by infusions and
      local hemostatic therapy in most cases result in reliable hemostasis of the upper
      parts of the gastrointestinal tract. The program of active measures is completed
      with the early enteral feeding with balanced nutritional mixtures.

PMID- 12216128
TI  - [Evaluation of the effectiveness of Dopplerography in patients with diffuse liver
      disease with portal hypertension syndrome].
AB  - Under analysis were the results of Dopplerography of the abdominal cavity vessels
      in 66 patients with liver cirrhosis and 14 patients with the extrahepatic portal
      block. The sensitivity of the method in diagnostics of the intrahepatic block was
      96.9%. The linear rate of the blood flow along the upper mesenterial vein was the
      most sensitive dopplerographic criterion of liver cirrhosis with the portal
      hypertension syndrome, the most specific test was the determination of the
      hepatic artery pulsativity index. A considerable decrease of the index of linear
      and volume rates of blood flow along the splenic vein and higher index of the
      splenic artery pulsativity were observed when the functional reserves of the
      liver decreased. A higher resistance index and the presence of the III degree
      gastroesophageal anastomoses are characteristic of the patients with bleedings
      from the veins of the esophagus and stomach.

PMID- 12216129
TI  - [Lengthy epidural blockade and intestinal motor function in the early
      postoperative period].
AB  - The telemetry method of registration of the intraintestinal pressure was used for
      the investigation of the motor function of the intestine under condition of
      continuous epidural blockade (CEB) with Trimekain at early terms after operations
      on the stomach for ulcer disease. It was found that the motor cycle structure of
      the small and sigmoid bowels within the first three days after resection of the
      stomach and truncal vagotomy was not substantially changed under the influence of
      CEB. A pronounced stimulating effect of the epidural blockade manifested itself
      as an improvement of the main quantitative parameters of intestinal motility. The
      character of these changes in the small and sigmoid bowels was the same and did
      not depend on intactness of vagus nerves. The combined mechanism of the influence
      of CEB on intestinal motility includes analgesia, improved respiratory function,
      greater volume of mesenterial circulation and the influence on the intramural
      nervous system and muscle apparatus of the intestine.

PMID- 12216130
TI  - [Diagnostic value of Dopplerography in mechanical intestinal blockage].
AB  - With intestinal obstruction taken into consideration, it is thought to be
      expedient to study changes to hemodynamics occurring in the basin of the superior
      mesenteric artery (SMA) with the help of dopplerography. A reliable elevation was
      noted in indices of the peak systolic circulation rate in SMA, mean linear
      circulation rate in SMA, correlation between the peak systolic rate in SMA and
      the systolic rate in the abdominal aorta, volume circulation rate in SMA. In
      addition, these indices were shown to depend on the level of the obstacle
      resulting in intestinal obstruction.

PMID- 12216131
TI  - [Role of the interferon system in the course of neglected forms of colorectal
      cancer].
AB  - Operations for neglected forms of colorectal carcinoma were performed on 66
      patients. The interferon status was determined before the operation, on the 1st,
      7th and 14th days after the operative intervention. "Viferon-2" was given to 18
      patients (starting from 2 days before the operation) with the daily dose
      1,000,000 IU. The investigation has shown that deep inhibition of production of
      interferon (alpha and beta by leukocytes increased risk of the development of
      postoperative pyo-inflammatory complications. Using the preparation "Viferon-2"
      is highly effective for prevention of such complications.

PMID- 12216132
TI  - [Prospects for saving vegetative nerves during operations for cancer of the lower
      rectum].
AB  - The aim of the work was to investigate the possibility to isolate and preserve
      the vegetative nerve of the pelvis in operations for low rectal cancer. In
      preparation of 17 corpses of people dead from causes not associated with a
      pathology of pelvic organs, mainly two forms of the structure of the superior
      hypogastric plexus were isolated--with many branches and with few branches. The
      pelvic promontory is taken as a reference-point. Frontal resection and
      extirpation of the rectum were fulfilled in 17 patients with low rectal cancer
      using the nerve-preserving technique of operation. Saving the vegetative nerves
      of the pelvis does not result in greater number of postoperative complications
      and positively influences the genitourinary function of the patients.

PMID- 12216133
TI  - [Transanal intervention for malignant nonepithelial rectal tumors].
AB  - The authors have analyzed their observations of 30 patients. Nonepithelial tumors
      were shown to be rare. Complex employment of endoscopic and X-ray methods of
      examination should be used for their diagnosis and differential diagnosis.
      Transanal interventions are thought to be palliative and can be used in patients
      with a high operative rick.

PMID- 12216134
TI  - [Technology for sclerosurgical treatment of upper veno-venous reflux of the large
      subcutaneous vein in varicose vein patients].
AB  - Under analysis were results of a complex ultrasound examination and the following
      treatment of 101 patients with varicose disease which had developed due to a high
      veno-venous ejection. The decision on the method of treatment depended on the
      variant of reflux spread and the degree of dilatation of the large subcutaneous
      vein. Four variants of spreading the reflux were established: in the inguinal
      area only (3.8%), along the femur to the level of the knee articulation (13.6%),
      femur and the upper third of the shin (66.8%), from the groin to the malleolus
      (15.8%). Selective interventions consisting in scleroobliteration or removal of
      the large subcutaneous vein within the limits of the femur or upper third of the
      shin were fulfilled in 84.2% of the patients. Sclerotherapy was used in veins
      having the diameter from 5 to 7 mm, sclerosurgery--with the diameter from 8 to 10
      mm, surgical treatment in veins with the diameter more than 10 mm. The
      effectiveness of liquidation of the reflux was 95.2%.

PMID- 12216136
TI  - [Reasons for lethal outcomes in severe multiple trauma].
AB  - The article is based on an analysis of causes and terms of lethal outcomes of 490
      patients after a severe combined trauma. Lethal outcome in 16.9% of the patients
      took place within an hour after admission to clinic. Within the first 24 hours
      died 50.2% of the patients, during the second day--8%, on the third day--8.4%. At
      the period from 3 to 7 days 14.3% of the patients died, during the second week-
      11.8% of the patients, 7.3% survived for more than 14 days. One direct cause of
      death was shown in 73.5% of cases, in 21.6%--there were two and in 4.9%--three
      causes. Acute massive blood loss was the direct cause of death of 43.9% of the
      patients, critical injury of the brain--in 25.1%, pneumonia--in 27.6%, sepsis--in
      6.9%. Altogether 26 causes of lethal outcomes were formulated.

PMID- 12216135
TI  - [Diagnostic criteria in choosing the method of operative treatment of diabetes
      mellitus with gangrene of the toes].
AB  - A variety of clinical variants, the absence of a common opinion on the terms and
      volume of surgery hamper the selection of the right strategy of treatment. Search
      for simple and open to general use methods of investigation of the state of
      hemocirculation in the extremity still remain actual which could help determine
      the surgical strategy at the early terms of treatment. Clinico-instrumental
      investigations in 60 patients with necrotic diseases of feet allowed detection of
      group differences in the character and degree of hemodynamic disorders and
      confirmed the necessity to differentiate gangrenous injury of the foot
      determining choice of the operative policy and probable prognosis of the outcome
      of the disease.

PMID- 12216137
TI  - [Surgical treatment of gunshot wounds to the colon].
AB  - An analysis of treatment of 76 patients with gunshot wounds of the colon was made
      as well as of the causes of the development of pyo-inflammatory complications.
      The morphological alterations of the intestine wall were studied in 22 patients
      at different distance from the wound at the light optical and electron
      microscopic levels. A conclusion is made that resection of the intestine with
      colostomy is necessary with regard to the zone of contusion. The formation of the
      colostomy should be performed by the proposed method which makes the restorative
      operation easier. Using these methods allowed the number of intraabdominal
      inflammatory operations to be reduced from 46.7% to 6.5% and lethality from 17.7%
      to 6.5%.

PMID- 12216138
TI  - [Use of ceramic endoprostheses in reconstructive surgery of the lower jaw in
      children].
AB  - The work analyses the possibility to use individually prepared ceramic
      endoprostheses in 6 children with a congenital or acquired pathology of the
      mandible. The operative methods with the application of ceramic endoprostheses
      are described which are characterized by less traumatic action and higher
      accuracy of correcting the defect or deformity of the mandible as compared with
      using biological plastic materials. This method of treatment can be recommended
      at the intermediate stages of the restorative reconstruction treatment of the
      mandible pathology in children.

PMID- 12216139
TI  - [Skin-muscle flaps in reconstructive plastic surgery of the breast].
AB  - The authors' experience with treatment of 20 patients has shown that musculo
      cutaneous thoracodorsal and TRAM flaps are the best methods of breast plasty
      after mastectomy. These operations provide oncologically safe performing radical
      mastectomy with the simultaneous restoration of the shape and volume of the
      breast and give reliable results. The additional application of the axillary
      fascial-fatty graft from the lateral surface of the chest improves the esthetic
      results of the breast reconstruction with the thoraco-dorsal flap. Using the TRAM
      flap for subcutaneous mastectomy can be the operation of choice in surgical
      rehabilitation of certain forms of tumor-like lesions of mammary glands.

PMID- 12216140
TI  - [Emergency endoprosthesis of the hip joint. Risk of hospital mortality].
AB  - An analysis of case histories of 854 patients operated upon for fractures of the
      proximal part of the femoral bone at the R.R. Vreden Research Institute of
      Traumatology and Orthopedics for the period from September 1997 to December 2000
      was made in order to assess the intrahospital lethality. The maximum season
      fluctuations were found to take place in October and March, minimum in September,
      December and April. The trend was characterized by a gradual rise from September
      to June. The authors associate these fluctuations with the action of external
      rhythmically changing factors, the growing trend--with the role of the factor of
      tiredness of the medical personnel. It was also shown that duration of the time
      interval from operation to the moment of death as well as the diversity of the
      value of this index was maximum in December-January and December correspondingly.

PMID- 12216141
TI  - [Intravascular photohemotherapy in the complex prophylaxis of purulent-septic
      complications after coronary shunting].
AB  - The article presents results of treatment of 78 patients with the history of
      coronary bypass operations for ischemic heart disease. There were 48 patients
      with high risk factors of the development of pyo-septic complications. Among them
      there were 27 patients treated by complex postoperative therapy including
      intravascular photomodification of blood. The intravascular irradiation of blood
      was shown to have a positive influence upon the development of the early
      postoperative period in this category of patients. The immunomodulating effect
      was noted due to a greater amount of activated lymphocytes and T-helpers in
      blood. The positive dynamics of immunological indices were in correspondence with
      the data of the clinical state, pyo-inflammatory complications were not
      registered in this group of patients. Early (on the 3rd-5th days) inclusion of
      the intravascular irradiation of blood in the complex postoperative therapy is
      thought to be expedient for the patients with high risk of pyo-inflammatory
      complications.

PMID- 12216142
TI  - [Clinical picture and treatment of mediastinitis after correction of congenital
      heart diseases in open heart surgery].
AB  - Postoperative purulent mediastinitis was observed by the authors in 43 out of
      1110 patients. Specific features of the clinical picture and course of this
      complication are described. The "closed" method of treatment was used in 20
      patients. Five of them died from intoxication and arrosive bleeding. The "open"
      method of treatment of mediastinitis was used in 23 patients with no lethal
      outcomes.

PMID- 12216143
TI  - [Victor Nikolaevich Shevkunenko (1872-1952)].

PMID- 12216144
TI  - [Treatment of purulent complications after high amputation of lower extremities
      in diabetes mellitus patients].
AB  - The authors describe results of treatment of purulent wounds after amputation of
      lower extremities in 10 patients with diabetes mellitus. Using daily
      necrectomies, ultrasonic cavitation of the wound surface, proteolytic enzymes
      resulted in rapid cleansing of the wounds of necrotic tissues. The early
      secondary sutures were put in 5 patients with active through drainage and laser
      irradiation of the sutured wound cavity with a conductor introduced through the
      drainage tube lumen. In all the cases the wounds were completely healed.

PMID- 12216145
TI  - [Intubation of the small intestine in emergency abdominal surgery].
AB  - The author's 33-years experiences with intubation of the small intestine include
      7,398 patients with acute surgical diseases and injuries of the abdomen. The
      absolute and relative indications for using this method and technical means of
      its performing are determined. During the first day after operation 74 of 398
      patients died because of their terminal state. The clinical effect of complete
      reestablishment of the motor-evacuatory function of the gastrointestinal tract
      followed by a discharge from the hospital was obtained in 324 patients. There
      were 8 complications as a result of an error during intubation of the small
      intestine with one lethal outcome. The author estimates the total intubation of
      the small intestine as one of the ways to reduce postoperative lethality in the
      complex treatment of the most sever group of patients with peritonitis and
      intestinal obstruction.

PMID- 12216146
TI  - [Gunshot wound of the inferior vena cava, liver, and duodenum].

PMID- 12216147
TI  - [Aorto-intestinal anastomosis as a complication of abdominal aortic aneurysm].

PMID- 12216148
TI  - [Combination of Garre stenosis of the small intestine and strangulated femoral
      hernia].

PMID- 12216149
TI  - [Treatment of patients with fecal incontinence].

PMID- 12216150
TI  - [Treatment of chronic anal fissure with topically applied nitroglycerin ointment.
      A systematic review of evidence-based results].
AB  - This study explores the evidence-based background for treating chronic anal
      fissure with topically applied nitroglycerin (NTG): in part the general effect of
      NTG and in part how its effect compares to that of surgery, which has been
      claimed to have long-term complications like incontinence for flatus and faeces.
      Ten randomised clinical trials published up to July 2001 were retrieved. In five
      of six studies, NTG had an effect on healing that was better than that of placebo
      or lignocaine. Headache is a common side effect of the treatment. Lateral
      internal sphincterotomy, the operation of choice for chronic anal fissure, and
      topical NTG were compared in four trials. Surgery had a better healing rate, but
      more late complications. The results suggest that in 31-65% of patients an
      operation could be avoided with NTG therapy. Topically applied 0.2% nitroglycerin
      three times a day for four weeks is therefore the primary choice in the treatment
      of anal fissures. But the possibility still remains that the observed effect of
      NTG may be the outcome of publication bias.

PMID- 12216151
TI  - [Nocturia. A common, but overlooked problem].
AB  - Nocturia is defined as waking at night to empty the bladder (1), irrespective of
      the number of times. Research has shown that it has a multifactorial aetiology
      and the need to wake up to urinate is probably because of an overproduction of
      urine or a reduced ability to store urine. Nocturia can occur at any age, but is
      particularly common in the elderly of both sexes. At present, both sufferers and
      physicians tend to consider it insignificant or a normal consequence of ageing,
      although it is not a trivial condition. Rising at night to urinate puts people at
      greater risk of falls (2), and has a detrimental effect on the quality of life,
      sleep patterns, and mortality (3). In young adults, the quality of life is
      particularly affected by persistent nocturia. Treatments (behaviour modification
      and pharmacological agents) are effective in many cases, although it is important
      to tailor treatment to the underlying pathophysiology.

PMID- 12216152
TI  - [Randomized comparison of CAM walker and light-weight plaster cast in the
      treatment of first-time Achilles tendon rupture].
AB  - INTRODUCTION: The aim of this study was to compare a CAM walker to a traditional
      cast. We expected the CAM walker to be comparable. MATERIAL AND METHODS: Fifty
      patients with a first time rupture of the Achilles tendon were randomised to
      either a cast or a CAM walker. Both groups were immobilised for eight weeks. All
      patients were examined four and 12 months after the injury. RESULTS: We found
      five reruptures in 29 patients treated with a cast (17%). No reruptures occurred
      in 21 patients treated with a CAM walker. The difference was not statistically
      significant (p = 0.066). There was no difference in age, sex, patient
      satisfaction, dominant/non dominant leg, muscle strength, or range of motion.
      DISCUSSION: The CAM walker is a useful alternative to a cast, with few
      complications and lower costs. Owing to the risk of type two error (44%), it is
      possible that we could have found a significant difference in the number of
      reruptures if the number of patients had been larger.

PMID- 12216153
TI  - [Thrombolysis in apoplexy. How big is the target group and how many benefit?].
AB  - INTRODUCTION: At present it is possible to dissolve cerebral blood clots with
      thrombolysis. This is a standard treatment in the USA and Canada for early onset
      ischaemic strokes within three hours of the stroke. Acceptance of thrombolysis is
      based on a single clinical trial. However, three other clinical trials have cast
      doubt on the benefit of the treatment and it has not yet been approved in Denmark
      and other countries. We sought to investigate the possible impact of thrombolysis
      in an unselected Danish stroke population. MATERIAL AND METHODS: This prospective
      study examined 502 unselected patients with acute stroke admitted over a period
      of eight months. The most important exclusion criteria from the North American
      trial with thrombolysis for acute ischaemic stroke were applied on the Danish
      cohort. The number of patients who might benefit from thrombolytic therapy was
      estimated from the North American trial, which reported a 32% relative increase
      in patients who would fully recover. RESULTS: Thirty-nine (8%) would be eligible
      for thrombolytic therapy. Thirteen patients (3%) would die, irrespective of
      treatment, and 11 patients (2%) would fully recover spontaneously. Three patients
      (0.6%) would benefit from thrombolytic therapy. In the ideal situation--all
      patients admitted in due time--11 patients (2.2%) would have benefited.
      CONCLUSION: Our study shows that few stroke patients would benefit from
      thrombolysis. The result is very well in line with the clinical experiences
      reported from the USA. Introduction of thrombolysis in Denmark to benefit the few
      would require extensive reorganisation of stroke care.

PMID- 12216154
TI  - [Self-expanding nitinol stents in the treatment of tracheobronchial stenoses].
AB  - INTRODUCTION: Several types of metal stents are available for the treatment of
      tracheobronchial stenosis. They can be self-expanding, balloon expandable,
      covered with a silicone membrane or uncovered. We have used a new self-expanding
      tracheobronchial nitinol wire stent since 1998, and our results are presented
      below. MATERIAL AND METHODS: Over a period of two years, 25 patients had a stent
      in the trachea or bronchus. The stents were inserted while the patients were
      under general anaesthesia, and flexible bronchoscopy was used. Respiratory
      function, histopathology, stent data, complications, and mortality were
      prospectively recorded. RESULTS: Eighteen patients had a malignant stenosis.
      Bronchial stenosis following a single lung transplantation (3) was the most
      frequent reason for a benign stenosis (7). Most of the patients had the stent
      placed in the trachea (14). All the stent insertions were performed without
      complications, and respiratory function was immediately improved in all patients
      except for two. The postoperative complications were inflammatory granuloma (5),
      stent dislocation (3), delayed expansion (2), stent rupture (1), and stent
      occlusion caused by retained secretions (1). DISCUSSION: The tracheobronchial
      ultraflex nitinol stent was easy to handle and was troublesome for only a few
      patients. Nitinol stents are considered to have a good biocompatibility, but 12%
      of the patients developed inflammatory granulations requiring electroresection.

PMID- 12216155
TI  - [Stapled anopexy for prolapsed hemorrhoids--a new operation].
AB  - INTRODUCTION: Haemorrhoidectomy is associated with pain and open wounds. A new
      closed technique uses an intraluminal stapler to replace the prolapsed
      haemorrhoidal tissue to a normal anatomical position (anopexy) and to interrupt
      the vessels. We report our results, including the learning curve. MATERIAL AND
      METHODS: Forty patients with grade 4 haemorrhoids underwent operation, 26 women,
      median age 47 years (33-86), and 14 men, median age 53 years (34-75). Outcome
      parameters were hospital stay, pain score, surgical anatomy score before and
      after the operation, and complications, symptom-control and patient satisfaction.
      RESULTS: Eleven patients left hospital on the day of operation, 19 the day after.
      The median pain score was 3 (2-10) for the first four days and 1 on day 7 (0-4).
      The postoperative surgical anatomy score was 1 (normal anus) in 24 patients, 2 in
      nine patients, which was not different significantly at follow up (p > 0.05).
      Postoperative bleeding required haemostasis in two patients. One patient had a
      stenosis temporarily, and two patients had persistent pain and faecal urgency,
      which disappeared. No sphincter lesions occurred. Control of symptoms and
      satisfaction were excellent in 20 patients, good in 11, and satisfactory in five.
      DISCUSSION: Stapled anopexy restored surgical anatomy towards normal, with
      moderate pain and few complications. Control of symptoms and patient-satisfaction
      was high. The procedure is a new option in the treatment of severe haemorrhoids
      rather than an alternative to open haemorrhoidectomy.

PMID- 12216156
TI  - [Sacral nerve stimulation in fecal incontinence].
AB  - INTRODUCTION: Sacral nerve stimulation for the treatment of faecal incontinence
      has gained increasing use in Europe over the last two years. Experience with the
      first patients treated in Denmark is described here. MATERIAL AND METHODS:
      Fourteen patients with severe faecal incontinence were given sacral nerve
      stimulation. The first treatment was temporary, and if this was successful they
      had a device for permanent stimulation implanted. RESULTS: The result of the test
      stimulation was good in ten of the 14 patients and a permanent system was
      implanted. After a median of 4.5 months' stimulation, nine of the ten patients
      continued to respond to respond well. DISCUSSION: Sacral nerve stimulation in the
      treatment of faecal incontinence shows promising results. Compared to other more
      advanced forms of treatment, this method is minimally invasive.

PMID- 12216157
TI  - [Semi-truths about semiconductors].

PMID- 12216158
TI  - [Fecal incontinence].

PMID- 12216159
TI  - [Depot steroids].

PMID- 12216160
TI  - [Consensus on ophthalmological screening in diabetes].

PMID- 12216161
TI  - [What's going on with rheumatology in Denmark today?].

PMID- 12216162
TI  - [Osteoarthritis and COX-2 inhibitors].

PMID- 12216163
TI  - [Treatment of osteoarthritis with COX-2 inhibitors: good for the stomach, but bad
      for the patient?].

PMID- 12216164
TI  - [Osteoarthritis].

PMID- 12216165
TI  - [Otitis media and antibiotics].

PMID- 12216166
TI  - [Whooping cough: an emerging problem].

PMID- 12216167
TI  - [International classification of functioning, disability and health (ICF) 2001].
AB  - The approach which had been being employed to date for dealing with and
      classifying those aspects related to health and disability have been revised and
      updated thanks to the World Health Organization (WHO) having drafted the
      International Classification of Functioning, Disability and Health, which has now
      been accepted 191 countries after revamping the prior model and reaching a
      consensus regarding a new international model for describing and measuring health
      and disability. As background information, it must be recalled that the
      Classification of Impairments, Disabilities and Handicaps (CIDH) previously in
      effect was first published by the WHO in 1980. The process of revising this
      classification has resulted in some changes of far-reaching importance. The
      change in the name has been aimed at reflecting the wish to replace the negative
      perspective of impairments, disabilities and handicaps for a more neutral view of
      structure and function, considering the positive perspectives of activities and
      of participation. Another new aspect has been that of including a section related
      to environmental factors in recognition of their importance, given that by
      interacting with the health condition they may give rise to a disability, or, at
      the opposite end of the scale, may restore functioning. The data available has
      enabled the WHO make estimates including that of some 500 million years of life
      being lost annually due to disabilities related to health problems, which totals
      over one half of the years lost annually due to premature deaths. The main
      objective of this new classification is that of providing the conceptual
      framework by means of unified, standardized language with a view to of the
      underlying challenges, setting out a valuable instrument of practical use in
      public health.

PMID- 12216168
TI  - [Demography, healht-related life style and history of tobacco consumption among
      occasional smokers in Spain].
AB  - BACKGROUND: This study describes the sociodemographic characteristics, health
      related lifestyle, and history of tobacco consumption of the occasional smokers
      in Spain, and examines whether they show differences against daily smokers.
      METHODS: Data were obtained from the National Health Survey of Spain, carried out
      in 1993 through household interviews on a sample representative of the non
      institutionalised population aged 16 year and older. Analyses were performed with
      logistic regression and adjusted for sociodemographic, health-state and life
      style variables. RESULTS: Out of the 6,668 smokers in the survey, occasional
      smokers were 9.2%, while daily smokers of < or = 5 cigarettes and > 5 cigarettes
      were 9.9% and 80.9%, respectively. As compared with daily smokers of > 5
      cigarettes, occasional smokers were more frequently women (odds ratio (0R): 2.12;
      CI95%: 1.72-2.61), younger (OR aged 25-44 versus 16-24 years: 0.75; 0.58-0.96),
      with lower alcohol consumption (p for linear trend: 0.0349), and higher leisure
      time physical activity (p for linear trend: < 0.0001). On the day they smoke,
      occasional smokers used to consume less cigarettes than daily smokers (p <
      0.0001). Occasional smokers were more frequent among young smokers (aged less
      than 20) with relatively short history of tobacco consumption (less than 20
      years), and also among older smokers (aged 65 year and older) with longer history
      of consumption (over 50 years). Daily smokers of < or = 5 cigarettes showed
      characteristics midway between those of occasional and daily smokers of > 5
      cigarettes. CONCLUSIONS: Occasional smokers show sociodemographic
      characteristics, health-related lifestyle, and history of tobacco consumption
      different from daily smokers. Such differences suggest that research and
      intervention programs specifically tailored to occasional smokers should be
      developed.

PMID- 12216169
TI  - [The influence of population structure on systemic antibiotic consumption.
      Valladolid, Spain].
AB  - BACKGROUND: The high degree to which systemic antibiotics are consumed in our
      country makes a study of those factors determining the spread thereof necessary.
      Different parameters are involved in the unequal spread of their consumption,
      including: a) the epidemiology of the infectious processes b) the population
      dependent factors and c) factors depending upon the prescribing physicians. This
      study is aimed at analyzing those determining factors depending upon the
      population (type of population and age). METHODS: A longitudinal retrospective
      study based on systemic antibiotic consumption data provided by the company
      International Marketing Services (IMS) for the January 1, 1996-December 31, 2000
      period. The consumption indicator used was the number of daily doses defined per
      1000 inhabitants/day (DID). Six geographical areas in the province of Valladolid
      were placed under study, three of which were urban and the other three mainly
      rural. RESULTS: The overall consumption by area was as follows: Medina del Campo
      (25.9DID), the capital city of Valladolid (23.4DID), Laguna de Duero (22.6DID),
      Northern Area (22.4DID), Southern Area (21.4DID) and, lastly, the Central Area
      (20.2DID). The specific consumption by areas revealed a greater consumption of
      amoxicillin in the three urban areas, amoxicillin-clavulanic acid and the major
      macrolides in Medina del Campo, quinolone antibiotics in the Northern Area and
      tetracyclines and sulfonamides in the capital city of Valladolid. CONCLUSIONS:
      Major overall consumption-related differences were found to exist among areas,
      the maximums being found in the urban areas. These differences were more marked
      on when studying the geographic spread of the consumption of the main active
      ingredients.

PMID- 12216170
TI  - [Estimating the coverage of systematic vaccinations among the Balearic Island
      infant population].
AB  - BACKGROUND: In order for vaccination programs to be carried out properly, it is
      essential for the vaccination coverage to be known. On the Balearic Islands, the
      reported coverage was much less than for the rest of Spain. The objective of this
      study is that of estimating the coverage of the vaccinations included on the
      recommended schedule up to 18 months of age (4 doses of oral polio, tetanus and
      diphtheria; 3 doses of whooping cough; 1 dose of measles, rubella and mumps).
      METHODS: A descriptive, cross-sectional study of the population base. The ideal
      time frequency distribution estimators and the corresponding confidence intervals
      were calculated at 95% (CI95%) for a sample of the resident two-year-old (born in
      1995) Balearic Island population selected by means of a single-stage conglomerate
      random sampling based on census sections. The National Public Health System and
      National Health Institute vaccination records were reviewed, the data from the
      vaccination document having been requested from the families and the clinical
      record from the private pediatricians by telephone. RESULTS: The sample included
      606 children, it having been possible to obtain full information on 532 children.
      Full information was obtained on 377 cases (62%) from the public health sector
      records. The least degree of coverage was found for the diphtheria vaccine, 518
      children having been fully vaccinated, 96.8% (CI95% = 94.8-98.1), the highest
      degree of coverage having been found for the whooping cough vaccine, 537
      children, 98.9% (CI95% = 97.5-99.5). CONCLUSIONS: Good vaccination coverage was
      found to exist on the Balearic Islands, being similar to what has been being
      estimated for Spain as a whole. The objective included within the Polio
      Eradication Plan is accomplished, very little information being gathered from the
      public sector.

PMID- 12216171
TI  - [A study of whooping cough epidemic outbreak in Castellon, Spain].
AB  - BACKGROUND: Based on the report of several cases at one school, a study of an
      epidemic outbreak was started for the purpose of characterizing this outbreak
      from the person, place and time standpoint, calculating the effectiveness of the
      immunization and the concordance of the cases with the positive result of the
      serological study. METHODS: A "case" is defined as being that individual who has
      a cough fasting for two weeks. A study is made of the spread of the disease by
      means of the epidemic curve and the effectiveness of the pertussis vaccine. The
      concordance of the cases and the positive serology is evaluated by way of the
      Kappa index. RESULTS: From among the students at several schools and those with
      whom they were living at the time, a total of 130 individuals were surveyed, 94
      of whom fit the "case" definition. The average age of the cases was 10.5 years of
      age, 42.6% being males and 84% school age children, 71.3% showing signs of recent
      infection (positive IgM), the average length of time since the last whooping
      cough immunization being 8.25 years. The effectiveness of the whooping cough
      booster is 66%. The concordance between the cases and the positive results of the
      serology reveals a Kappa = 0.45. No B. Pertussis was isolated in the 25 throat
      swab samples. CONCLUSIONS: Classrooms and the family environment are a factor in
      spreading this disease. The including of a booster at 18 months improves the
      effectiveness of the whooping cough immunization. The isolation of B. Pertussis
      is not very frequent, and the serology may be an alternative when this disease is
      clinically suspected.

PMID- 12216172
TI  - [Readability of health web pages for patients and readers among the general
      population].
AB  - BACKGROUND: Internet is becoming now becoming one of the major healthcare
      information sources. Aside from this popularity, new questions are now coming to
      bear, such as the quality of the information provided or its ability to convey
      knowledge. The purpose of this study is that of gauging the degree of readability
      of this information for patients which is accessible on the Internet in Spanish.
      METHODS: A total of 112 webpages dealing with seven (7) chronic diseases were
      selected. Based on the Microsoft Word readability statistics, we recovered the
      data of the number of syllables and sentences in the first 100 words in each
      document. For calculating readability, we used the adaptation of the Flesch
      degree formula for the Spanish language devised by Fernandez Huerta. RESULTS: The
      mean readability of the documents is 65.16 (+/- 14.75), thus corresponding to a
      standard level, in other words, a thirteen-year-old's reading level. CONCLUSIONS:
      Although the readability scores found for the documents analyzed are good, they
      are not optimum for the users searching for health-related information on the
      Internet. It is essential that these informative documents be adapted to these
      users' readability level.. The need for studies evaluating the consequences
      entailed in the low degree of health-related literacy entails the incorrect use
      of medications, mistakes in preparing for diagnostic tests and an increase in the
      costs of healthcare services.

PMID- 12216173
TI  - [Vaccine storage cold chain at primary care centers in one area of Madrid:
      keeping the chain intact and degree of knowledge].
AB  - BACKGROUND: Vaccines are heat-labile medications, and to guarantee their
      immunogenicity and safeguarding effectiveness as part of immunization programs,
      it is absolutely essential that the "Cold Chain" go unbroken. Fundamental thereto
      is the personnel responsible for the vaccines, who must know the stability
      related characteristics of each preparation so as to prevent handling errors. The
      purpose of this study was that of ascertaining how the cold chain is kept intact
      in primary care systems in one healthcare area of the Autonomous Community of
      Madrid, as well as determining the degree of information possessed by those
      responsible for vaccines as far as their heat-stability is concerned. METHODS: A
      cross-sectional study has been made at 46 primary care vaccination points. The
      data was gathered by means of a personal interview by one single researcher.
      RESULTS: The participation rate was 93.5% (43/46). In all cases, there was a
      maximum and minimum thermometer and monthly temperature record. An unsuitable
      temperature was found in three cases (6.97%). The percentage of professionals who
      were aware of the effect freezing has on vaccines varied greatly: 53.5%, 51.2%,
      44.2% and 53.5% for diphtheria-tetanus-pertussis (DTP), hepatitis B (HBV), oral
      polio (OPV) and measles-mumps-rubella (MMR) respectively. And only 32% were
      familiar with the shake test. CONCLUSION: The professionals were found to be
      properly trained regarding the effect which high temperatures have on vaccines,
      but it is necessary for their training with regard to the instability of adsorbed
      preparations when frozen must be further strengthened.

PMID- 12216174
TI  - [The Madrid autonomous community epidemiological bulletin. A survey on its
      dissemination and opinion thereof on among primary care physicians for the year
      2000].
AB  - BACKGROUND: The Autonomous Community of Madrid Epidemiological Bulletin is the
      main communications link between epidemiological monitoring system and health
      care professionals. The purpose of this study is that of ascertaining the
      dissemination and opinion of this Autonomous Community of Madrid Epidemiological
      Bulletin among primary care physicians for the purpose of adapting this
      publication to its readers' interests. METHOD: A telephone survey among primary
      care physicians in the Autonomous Community of Madrid, asking how often they read
      the Bulletin, the interest and usefulness of the information included in it. The
      sample size was estimated at 346 physicians. A two-stage sampling process was
      carried out-by cluster sampling in the first stage, randomly selecting 125 health
      care centers and 2.7 physicians per center, 17% being primary care team
      coordinators. A comparison is made of the results among physicians and
      coordinators by means of the Chi-square and Fisher's Exact Test method, with Epi
      Info v.6. RESULTS: A total of 305 surveys were conducted (245 physicians and 60
      coordinators). There was an awareness of the existence of the Autonomous
      Community of Madrid Epidemiological Bulletin on the part of 91.5% (CI 95%: 88.1
      94.8), and 27.2% (CI 95%: 21.9-32.5) were familiar with more than 50% of the last
      issues published. A total of 92.4% (CI 95%: 89.4-95.8) considered the Bulletin to
      be interesting or highly interesting, grading its usefulness an average of 3.5 on
      a maximum scale of 5. Of the permanent sections, the most highly-valued was
      Epidemic Outbreaks, those reports related to meningococcal infection,
      tuberculosis and HIV/AIDS being the most highly-valued. CONCLUSIONS: The
      Autonomous Community of Madrid Epidemiological Bulletin is a publication which,
      although not widely-known by the primary care physicians in the Community, is
      well-valued when it is read, thus being a useful feedback tool within the
      Epidemiological Monitoring System.

PMID- 12216176
TI  - Midwife strife.

PMID- 12216175
TI  - [The development of the price index for the consumption of tobacco and alcoholic
      beverages].

PMID- 12216177
TI  - Fair lady.

PMID- 12216178
TI  - Take my advice.

PMID- 12216179
TI  - Dying to know.

PMID- 12216180
TI  - Meal appeal.

PMID- 12216181
TI  - Telemedicine in rural care. Part 1: Developing and evaluating a nurse-led
      initiative.
AB  - AIM: To develop and evaluate a nurse-led telemedicine service over a six-month
      period, linking the senior citizens of a rural village with the town-based
      general practice. METHOD: Patients, doctors and nurses were asked to complete a
      questionnaire following video-link sessions. Interviews were also carried out at
      home with patients, while interviews with nurses and doctors took place in the
      workplace. RESULTS: Of the 173 consultations with villagers aged over 65, 29 (17
      per cent) were conducted by video-link. All those who used this service were sent
      questionnaires and 18 were returned (62 per cent). Seven of the patients who had
      received one video-link consultation were interviewed in their homes. All of the
      patients initially found the video consultation experience strange. Generally,
      patients found the nurses to have a pivotal role in explaining the service and
      interpreting their needs. All those interviewed said they would use the service
      again. The GPs spoke favourably of the service and said that it had saved them
      time. The nurses involved were positive about the service. Negative comments
      generally related to technology, for example picture and sound quality.
      CONCLUSION: All involved in the nurse-led telemedicine service viewed it
      favourably and patients said that they would use it again. Part two, to be
      published in next week's Nursing Standard, will discuss the findings of the
      evaluation in relation to the wider picture of nursing involvement in
      teleconsultation.

PMID- 12216182
TI  - Ebola haemorrhagic fever.
AB  - This article focuses on the management of a patient who was admitted to The Aga
      Khan Hospital in Dar es Salaam, Tanzania, with suspected Ebola haemorrhagic fever
      (Ebola HF). It defines the disease, symptoms and how it is spread, diagnosed,
      treated and prevented. Recommendations are made for management of Ebola HF in a
      hospital setting.

PMID- 12216183
TI  - Sharps injury: prevention and management.
AB  - Nurses are at risk of infection through injuries caused by infected sharps and
      needles. The authors discuss the prevention and management of such injuries.

PMID- 12216184
TI  - Maximum intensity. Interview by Frances Pickersgill.

PMID- 12216185
TI  - Carers in court. Interview by Colin Parish.

PMID- 12216186
TI  - In on the act.

PMID- 12216188
TI  - At the double.

PMID- 12216187
TI  - Power to the patients.

PMID- 12216189
TI  - What is this thing called nursing?

PMID- 12216190
TI  - Look out for signs of distress.

PMID- 12216191
TI  - Evaluating a walk-in clinic for detecting skin cancers.
AB  - AIM: To evaluate the effectiveness of a walk-in clinic in detecting skin cancers.
      METHOD: Questionnaires were completed by 283 patients attending the walk-in
      clinic at a dermatology outpatients department. The questionnaire was used to
      gather data on demographics, sun exposure, and personal and family history of
      skin cancers. Completion of the questionnaire was followed by an examination by a
      dermatologist. RESULTS: Three patients were diagnosed with malignant melanoma as
      a result of evaluation at the walk-in clinic. CONCLUSION: The walk-in clinic was
      an effective method of identifying patients with melanomas who might not have
      seen a GP. The authors believe that though effective at the screening, the clinic
      could be refined and improved.

PMID- 12216192
TI  - Autoimmune disorders.
AB  - Autoimmune disorders affect people of all ages, ethnicity, social class and
      gender. The authors briefly review the normal immune response and consider how
      this might break down, resulting in autoimmune disorders. Susceptibility of
      individuals to such disorders is discussed and examples of specific conditions
      are outlined.

PMID- 12216193
TI  - The supply and fitting of a temporary breast prosthesis.
AB  - The fitting of soft breast prostheses is an essential nursing duty on breast
      cancer surgery wards, but it appears to be performed on an ad hoc basis, without
      evidence-based guidelines. A diagnosis of breast cancer carries enormous
      implications for the patient in terms of physical and psychological health. For
      this reason, it is vital that nurses respond sensitively to these needs and
      assist women to cope with the changes in body image. This includes ensuring that
      knowledge underpins practice when fitting the soft breast prosthesis. This
      article outlines a 12-point plan devised by the authors, giving guidance on how
      to fit temporary breast prostheses.

PMID- 12216194
TI  - Understanding the challenge of Parkinson's disease.
AB  - Parkinson's disease is a progressive, fluctuating neurological condition for
      which there is no cure. The nurse's role in caring for patients with the disease
      is to enable them to have as good a quality of life as possible, based on
      appropriate assessment and management strategies.

PMID- 12216195
TI  - All things being equal. Interview by Lynne Pearce.

PMID- 12216196
TI  - Leading questions.

PMID- 12216197
TI  - A violent reaction.

PMID- 12216198
TI  - Who's minding the children?

PMID- 12216199
TI  - The privileged carer.

PMID- 12216200
TI  - The human factor.

PMID- 12216201
TI  - Training needs of psychiatric intensive care staff.
AB  - AIM: A survey was carried out to identify the education and training needs of
      psychiatric intensive care staff and the preferred type of training course.
      Demand for a specific psychiatric intensive care unit (PICU)/lowsecure training
      course was also examined. METHOD: A convenience sample was taken from delegates
      attending a National Association of Psychiatric Intensive Care Units (NAPICUs)
      conference. Questionnaires were given to 130 delegates and a mail-shot was sent
      to ward managers on 13 PICUs in London. RESULTS: The findings were that staff
      wanted further training in four main areas: the management of violence and
      aggression; psychological therapies; communication and engagement skills; and
      rapid tranquillisation. Most respondents indicated that they would like a course
      developed specifically for PICU staff at degree level in modular format.
      CONCLUSION: This small-scale study highlights the need for further provision of
      training for PICU staff and provides an insight into their education and training
      needs. The findings could have significant implications for developing new
      approaches to education and training for practitioners working with severely ill
      psychiatric patients.

PMID- 12216202
TI  - Developing benchmarks for prior learning assessment. Part 1: Research.
AB  - AIM: The aim of the study was to develop and promote national benchmarks for
      those engaged in accreditation of prior learning (APL) termed 'prior learning
      assessment and recognition' (PLAR) assessment in Canada, in all sectors and
      communities. The study objectives were to gain practitioner consensus on the
      development of benchmarks for APL (PLAR) across Canada; produce a guide to
      support the implementation of national benchmarks; make recommendations for the
      promotion of the national benchmarks; and distribute the guide. The study also
      investigated the feasibility of developing a system to confirm the competence of
      APL (PLAR) practitioners, based on nationally agreed benchmarks for practice.
      METHOD: A qualitative research strategy was developed, which used a benchmarking
      survey and focus groups as the primary research tools. These were applied to a
      purposive sample of APL practitioners (n = 91). The participants were identified
      through the use of an initial screening survey. RESULTS: Respondents indicated
      that in Canada, PLAR is used in a variety of ways to assist with individual and
      personal growth for human resource development, the preparation of professionals
      and the achievement of academic credit. The findings of the focus groups are
      summarised using a SWOT analysis CONCLUSION: The study identified that the main
      functions of the PLAR practitioners are to prepare individuals for assessment and
      conduct assessments. Although practitioners should be made aware of the potential
      conflicts in undertaking combined roles, they should be encouraged to develop
      confidence in both functions.

PMID- 12216203
TI  - Promoting healthy skin in older people.
AB  - As people age, natural changes occur in the skin that put older people at risk of
      poor or compromised skin health.

PMID- 12216204
TI  - Safe and sound.

PMID- 12216205
TI  - From victim to survivor.

PMID- 12216206
TI  - Tricia's medicine.

PMID- 12216207
TI  - Under lock and key.

PMID- 12216208
TI  - Pain drain.

PMID- 12216209
TI  - Advanced nursing practice in intermediate care.
AB  - Initiatives in intermediate care are mainly nurse-led and, as nursing practice
      becomes more advanced, nurses need to consider the professional, ethical and
      legal implications.

PMID- 12216211
TI  - A proactive approach to wound infection.
AB  - The management and treatment of infection is a complex and important area in
      tissue viability nursing. Andrew Kingsley discusses the value of microbiology to
      clinical practice and the importance of adopting a proactive approach to the
      management of infected wounds using an infection continuum and algorithm to help
      promote effective care.

PMID- 12216210
TI  - Phobias: nature, assessment and treatment.
AB  - Phobias are anxiety disorders that can have a significant impact on a person's
      lifestyle, due to the distress and symptoms suffered. This article discusses the
      characteristics, assessment and treatment of the three classified phobias, as
      well as self-help interventions.

PMID- 12216212
TI  - Promoting evidence-based education in tissue viability.
AB  - The introduction of the UKCC Scope of Professional Practice (1992a) has
      encouraged many practitioners to develop their practice in specific areas of
      nursing including tissue viability. As a result, practitioners wish to develop
      their knowledge to ensure they deliver the most effective evidence-based care to
      patients. The author discusses the importance of evidence-based tissue viability
      education, which integrates input from educationalists and clinicians.

PMID- 12216213
TI  - The management of venous leg ulcers: a project to improve care.
AB  - This article describes a two-year project to develop resources for the
      improvement of leg ulcer management. It was felt that an audit tool and
      complementary resources, such as a resource pack and implementation guide, could
      help practitioners to implement clinical guidelines on leg ulcer management in
      practice. The audit results from the pilot project are briefly described and
      discussed in terms of informing future work.

PMID- 12216214
TI  - Conceiving change. Interview by Frances Pickersgill.

PMID- 12216215
TI  - The more the merrier.

PMID- 12216216
TI  - Silent epidemic.

PMID- 12216217
TI  - Losing ground.

PMID- 12216218
TI  - Step by step.

PMID- 12216219
TI  - The attributes of effective clinical nurse leaders.
AB  - AIM: To identify the attributes of effective clinical nurse leaders. METHOD: A
      grounded theory research approach was adopted, using two research techniques:
      observation and interview. RESULTS: The literature review revealed that the role
      of the clinical nurse leader was ill-defined and addressed only in sparse,
      opinion-based literature. Novel outcomes of the research included: Identifying
      five attributes of effective clinical nurse leaders--highlighting, respecting,
      influencing, creativity and supporting. Distinguishing five typologies of
      effective clinical nurse leaders--discoverer, valuer, enabler, shaper and
      modifier. Elucidating factors that constrain and facilitate the development of
      effective clinical nurse leadership. CONCLUSION: The results imply that to
      enhance clinical nursing, leadership factors that enable and constrain clinical
      nursing leadership have to be identified and acted upon by individuals and those
      who they report to professionally.

PMID- 12216220
TI  - Developing benchmarks for prior learning assessment. Part 2: Practitioners.
AB  - Part 1 of this article examined a study into the use of benchmarking for prior
      learning assessment (PLA). This article outlines the benchmarks and practitioner
      guidelines that emerged from the study. The guidance is based on the benchmarks
      for practice and is intended to encourage PLA practitioners and adult learners to
      purposefully apply proven assessment theory to a variety of personal and
      professional goals and needs, by developing a portfolio. The basic principles and
      processes necessary for effective, systematic assessment of prior learning are
      identified and discussed.

PMID- 12216221
TI  - Understanding allergies and their treatment.
AB  - Allergies are common and although their effects are often minor, they can be life
      threatening. The authors discuss the background to allergy and give guidance for
      prevention and management.

PMID- 12216222
TI  - Statistical assault.

PMID- 12216223
TI  - Bully at work.

PMID- 12216224
TI  - Forced to leave my job.

PMID- 12216225
TI  - Breath of fresh air. Interview by Catharine Sadler.

PMID- 12216226
TI  - Pioneering practice. Interview by Alison Moore.

PMID- 12216227
TI  - . . . and it's personal.

PMID- 12216228
TI  - Think ahead.

PMID- 12216229
TI  - Length of stay in community hospitals.
AB  - AIM: To identify the factors that contribute to variation in length of stay in
      hospital. METHOD: After a pilot study, an audit was undertaken in 11 community
      hospitals in a single trust over an eight-week period. Each ward was audited
      once. During the audit period 202 patients' records were reviewed, of which 71
      were GP admissions and 131 were consultant admissions. RESULTS: Patients admitted
      to community hospitals were older, predominantly female, classed as at risk of
      malnutrition and had a reduced functional capacity. An increased length of stay
      could also be due to limited evidence of discharge planning on transfer from
      acute or residential homes, a lack of information about patients' social
      circumstances and how the discharge process was progressed, delay from referral
      to assessment by the multidisciplinary team, and pressure ulcers on admission to
      hospital. CONCLUSION: Recommendations for practice are: improved documentation,
      including an integrated discharge care pathway that is transferable across health
      and social care; multidisciplinary records; clinical leadership; adapting the
      current audit tool; and undertaking another audit after the recommendations have
      been implemented.

PMID- 12216230
TI  - Vaccination in older people.
AB  - Vaccinating older people remains a priority in the specialty of public health.
      However, medical practitioners, pharmacists, carers and family members and the
      media need to make a special effort to inform and educate older people of the
      need to protect themselves against certain diseases, such as influenza,
      pneumococcal pneumonia and tetanus. These conditions pose particular health risks
      to older people in terms of the high risk of developing serious complications.

PMID- 12216231
TI  - Bronchodilators: implications for nursing practice.
AB  - Beta2-adrenoreceptor agonists are the most widely prescribed bronchodilators and
      are used for symptomatic control and as 'rescue' medication for people with
      asthma and other chronic conditions affecting the airways. The authors describe
      the clinical uses, mechanism of action and potential side effects of these
      agents, emphasising the nurse's role in monitoring therapy.

PMID- 12216232
TI  - Agony of the innocent.

PMID- 12216233
TI  - Showing the way.

PMID- 12216234
TI  - Get down to the nitty gritty.

PMID- 12216235
TI  - Understanding constipation.

PMID- 12216236
TI  - Assessing the strengths and weaknesses of action research.
AB  - BACKGROUND: Proponents of action research claim that it is not just for
      researchers, but helps to empower research participants to make changes in
      practice. This literature review examines some of the evidence for and against a
      research methodology that might still be unfamiliar to many nurses. CONCLUSION:
      Action research often lends itself to small-scale studies and is time-consuming.
      The value of such a methodology is that it provides a powerful means of improving
      and enhancing practice.

PMID- 12216237
TI  - Using the Web to develop an EN conversion course.
AB  - This article describes the use of a web-based environment to develop a
      modularised enrolled nurse (EN) conversion programme. It details the development
      process and the reasons for choosing a web-based environment for the programme.
      In the age of multimedia developments, sharing the processes and the problems
      encountered will benefit those who access future programmes.

PMID- 12216238
TI  - Introducing non-invasive positive pressure ventilation.
AB  - Non-invasive ventilation techniques provide and enhance alveolar ventilation
      without the need for an endotracheal airway. These techniques are increasingly
      being used by nurses to manage patients with type 2 respiratory failure. The
      author outlines the advantages of, and criteria and contraindications for, using
      bi-level positive airway pressure (BiPAP).

PMID- 12216240
TI  - Hearing aids.

PMID- 12216241
TI  - Chaos theory.

PMID- 12216239
TI  - Malaria.
AB  - Malaria is a common and dangerous tropical disease, caused by a parasite
      transmitted to humans through the bite of the anopheles mosquito. This article
      reviews the prevention, symptoms, diagnosis and treatment of malaria, and
      outlines key aspects of pre-travel advice.

PMID- 12216242
TI  - Starvation.

PMID- 12216243
TI  - Erectile dysfunction.

PMID- 12216244
TI  - MRSA in intensive care.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is becoming more prevalent,
      particularly in intensive care settings. To prevent its transmission, all
      patients should undergo the same infection control procedures that they would if
      they carried the infection. Continuing education programmes can help to increase
      awareness among hospital staff.

PMID- 12216245
TI  - Dealing with scabies.
AB  - The challenge for nurses in hospital and community settings is to recognise
      scabies, deal with it appropriately and to help educate those who are most
      vulnerable.

PMID- 12216246
TI  - What the papers say.

PMID- 12216247
TI  - Rural nightmare.

PMID- 12216248
TI  - Community carousel.

PMID- 12216249
TI  - Stress and how to beat it.

PMID- 12216250
TI  - Look on the bright side.

PMID- 12216251
TI  - Stress factor.

PMID- 12216252
TI  - The significance of drinking context for home detoxification.
AB  - AIM: A research study was conducted to examine the concordance between the
      severity of alcohol dependence and the nursing activity found in an episode of
      care for home detoxification. This article is based on an audit of clients'
      records which formed part of the research project. The aim was establish the
      degree of dependence through the application of a severity assessment instrument
      and to relate this to the level of nursing activity from the recorded client
      contacts. METHOD: Quantitative and qualitative data were obtained from a clinical
      audit of each client's nursing and medical notes. Examination of the data
      provided an insight into the client's drinking context. RESULTS: The findings
      demonstrated substantial levels of drinking at home, drinking alone, and all-day
      drinking. This could have significant implications for traditional methods of
      assessment and the routine practice of home detoxification. CONCLUSION: Evidence
      from the audit suggests that criteria such as environmental and psychosocial
      issues should be considered alongside physical and psychological aspects as part
      of the assessment criteria for home detoxification. Some clients might benefit
      from alternative strategies such as outpatient detoxification, day-patient
      attendance detoxification, or specialist inpatient treatment rather than home
      detoxification.

PMID- 12216253
TI  - An overview of education and 'new genetics'.
AB  - Research and development in the field of genetics and the Human Genome Project
      will have a major impact on the future of health care and the services on offer
      for users. The authors discuss the importance of educating nurses about genetic
      developments so that they can apply this knowledge to practice.

PMID- 12216254
TI  - The Pendine pathways project in the independent sector.
AB  - Recruitment and retention of staff, and the drive to provide quality care are
      challenges currently faced by nursing and residential homes in the independent
      sector. This article describes an innovative approach to tackling these issues.
      Under a teaching company scheme, a partnership was formed between the Pendine
      Park Nursing Home and the Centre for Learning Development to develop care and
      career pathways that are specific to the independent sector.

PMID- 12216255
TI  - Developing an integrated nursing team approach.
AB  - Nursing Standard recently published a literature search that explored different
      models of integrated nursing and more traditional models of community nursing in
      primary care (Baileff 2000). Models of change for implementing integrated nursing
      were also examined. This article aims to explore the development of an integrated
      nursing team in a healthcare centre in Northampton.

PMID- 12216256
TI  - Lower limb amputation.
AB  - The decision to amputate is a difficult one, but in some cases, amputation can
      greatly improve the patient's quality of life. Jo Gibson discusses the nursing
      care of patients undergoing amputation, with a view to helping them adjust to
      their changed circumstances.

PMID- 12216257
TI  - Sweet relief.

PMID- 12216258
TI  - Poor performance.

PMID- 12216260
TI  - Teen spirit.

PMID- 12216259
TI  - Made to order. Interview by Catharine Sadler.

PMID- 12216261
TI  - Signing on.

PMID- 12216262
TI  - Be prepared.

PMID- 12216263
TI  - Fighting fraud.

PMID- 12216265
TI  - Telemedicine in rural care. Part 2: Assessing the wider issues.
AB  - BACKGROUND: The first article about this development (Macduff et al 2001)
      described the evolution of a nurse-led telemedicine service in the village of
      Hamlet (population 1,600), north-east Scotland, and presented the findings of an
      evaluation study. In this second article, those findings are discussed in
      relation to the wider picture of nursing involvement in teleconsultation. The
      village has no medical practice or pharmacy and the majority of Hamlet's
      residents aged over 65 are registered with the Bradieslea Road surgery, one of
      three general practices six miles away in the town of Bradieslea. The community
      nursing service is based in small rooms at a sheltered housing complex in the
      village. This service covers all patients in the Hamlet area. It is staffed by
      one full-time district nurse/health visitor (who acts as team leader) and one
      part-time district nurse. Both are qualified nurse prescribers. CONCLUSION:
      Opportunities now exist for nurses to use teleconsultation for the benefit of
      their patients. A systematic development of this type of nursing role through
      integration with broader service development would be valuable.

PMID- 12216266
TI  - Cultural sensitivity: a practical approach to improving services.
AB  - Reports commissioned by the Department of Health (Acheson 1998, Alexander 1999)
      have highlighted the failure of the NHS to provide culturally sensitive services
      for black and Asian patients. Cultural sensitivity in nursing is the provision of
      care that is sensitive to the needs of clients from all cultures. The authors
      outline the action taken to improve cultural sensitivity in a community hospital.

PMID- 12216267
TI  - The influence of professional roles on clinical supervision.
AB  - Clinical supervision involves establishing professional relationships that,
      notwithstanding other benefits, are concerned with safe and effective nursing
      practice. It is important that supervisors and supervisees are able to work
      together constructively. Supervisors and supervisees should, therefore, consider
      their roles and responsibilities outside supervision and how these might
      influence the supervision relationship. This article draws on the author's
      personal experiences in the roles of supervisor and supervisee, as well as using
      ideas from counselling, social work and nursing. Issues related to safe
      professional practice are also explored. Protocols could be devised offering
      guidance regarding who should undertake the role of supervisor.

PMID- 12216268
TI  - Spasticity: a common symptom of multiple sclerosis.
AB  - Spasticity is a common symptom in people with multiple sclerosis. The nurse plays
      a vital role in the assessment and ongoing management of spasticity.

PMID- 12216269
TI  - Intravenous long-lines in children with cystic fibrosis: a multidisciplinary
      approach.

PMID- 12216270
TI  - The heart in cystic fibrosis.

PMID- 12216271
TI  - Mechanisms of antibiotic resistance in Pseudomonas aeruginosa.

PMID- 12216272
TI  - Macrolides in the respiratory tract in cystic fibrosis.

PMID- 12216273
TI  - National Health Services for patients with cystic fibrosis: the good, the bad and
      the ugly.

PMID- 12216275
TI  - Patient advocacy and cystic fibrosis: political correctness or a real force for
      good?

PMID- 12216274
TI  - Health service careers for people with cystic fibrosis.

PMID- 12216277
TI  - The birds from Las Hoyas.
AB  - Information on the first steps of the avian evolutionary history has dramatically
      increased during the last few years. The fossil record provides a general view of
      the morphological changes of the avian flight apparatus from nonvolant ancestors
      (non-avian theropod dinosaurs) to the first derived fliers of the Early
      Cretaceous. The Las Hoyas bird record includes three genera: Iberomesornis,
      Concornis and Eoalulavis. This fossil material has yielded information about the
      early avian evolutionary history. These Early Cretaceous birds (some 120 Myr old)
      had a wingbeat cycle and breathing devices similar to those of extant birds. The
      function of the rectricial fan was also similar. In the evolutionary transition
      from cursorial ancestors to derived fliers it is possible to verify a trend to
      increase lift. Primitive wing aspect ratio morphotypes were elliptical ones,
      other derived morphotypes appeared, for example, in the Neornithes (extant
      birds). Some primitive fliers, like the Las Hoyas genus Eoalulavis, had an alula
      (feathers attached to the first digit of the hand) similar to that of present day
      birds, indicating braking and manoeuvring skills similar to those of their extant
      relatives. Primitive avian life habits are poorly understood. Some evidence from
      the Las Hoyas bird record indicates that Early Cretaceous birds were present in
      the trophic chains.

PMID- 12216278
TI  - Clinical aspects of photodynamic therapy.
AB  - Photodynamic therapy is a method for local destruction of tissue or organisms by
      generating toxic oxygen and other reactive species using light absorbed by an
      administered or an endogenously generated photosensitiser. It is a highly
      promising treatment for patients with cancer. More recently it has found
      increasing use as a method of therapy for non-cancerous illnesses. It depends on
      the exploitation of natural and vital reactions widespread in nature that have
      driven and preserved life on this planet. Following administration of a
      photosensitiser or its precursor there is an accumulation or retention in areas
      of cancer and disease relative to adjacent normal tissue. The photosensitiser is
      inactive until irradiated by light, following which cellular destruction occurs.
      The clear attraction of this method is the possibility of some targeting of the
      disease by drug and by the area irradiated. This explanation although
      oversimplified has been the reason for the scientific and clinical interest in
      photodynamic therapy. An understanding of evolutionary photobiology is enormously
      helpful to understand disease response and clinical outcomes.

PMID- 12216276
TI  - New therapeutic approaches for cystic fibrosis lung disease.

PMID- 12216279
TI  - Development of the sensory organs.
AB  - The sensory organs--the eye, ear, and nose- are formed, in part, from ectodermal
      thickenings: placodes. Their development is distinct from that of other regions
      of the developing body and they are essential for the development of other
      structures. For example, the olfactory placode which gives rise to the nose is
      essential for the functional development of the reproductive organs and hence
      fertility. Recently much progress has been made in the understanding of placode
      development, at both a molecular and embryological level. This is important as
      abnormal development of placodes occurs in a number of human syndromes.
      Furthermore, knowledge of placode development will give insight into therapeutic
      strategies to prevent degenerative change such as deafness. This review
      highlights the current knowledge of placode development and the future challenges
      in unravelling the cascades of signalling interactions that control development
      of these unique structures.

PMID- 12216280
TI  - A new method for measuring intramolecular charge transfer.
AB  - The direct measurement of intramolecular electron transfer through detection of
      the electromagnetic (EM) waveform that is emitted during this process is
      reviewed. The waveform is detected in the time-domain via free-space electro
      optic sampling and then related to the dynamics of the charge transfer event.
      Electromagnetic generation from two systems, Betaine-30 in chloroform and DMANS
      in toluene, are studied to illustrate this technique. A finite-difference time
      domain calculation with a time-dependent polarization is used to model the EM
      generation and propagation through the solution. This method is very general
      since the movement of charge itself generates the EM waveform, and is sensitive
      to charge transfer occurring on a 0.1-10 ps timescale. The potential for studying
      the primary steps of charge transfer in photosynthetic bacteria is also
      discussed.

PMID- 12216281
TI  - Journey of discovery. Interview by Judy Czylok.

PMID- 12216282
TI  - You've got the power.

PMID- 12216283
TI  - We all make mistakes....

PMID- 12216284
TI  - All dressed up.

PMID- 12216287
TI  - Nursing development units: progress and developments.
AB  - Nursing development units (NDUs) are centres where groups of nurses, midwives,
      public health nurses and health visitors use a comprehensive planned strategy to
      develop themselves and their practice. Some of the early defining work on NDUs is
      considered and a brief history is outlined in this article. The strategic
      approach taken by the Eastern Health Shared Services in Dublin has led to the
      development of many NDUs in the Dublin area over a five-year period. The NDUs are
      based on a strategic, supportive approach. Six now exist in the state-funded
      health service system, but the project has also been widened to include the
      private and voluntary sectors and this has stimulated several other units to
      emerge. Focus group work with NDU leaders and facilitators has led to a gradual
      redefining of the principles of NDUs and the emergence of an accreditation system
      run by the board. The authors summarise these findings.

PMID- 12216286
TI  - Challenging the myth of the 12-hour shift: a pilot evaluation.
AB  - AIM: The aim of this pilot evaluation was to assess whether changing a nursing
      shift pattern to incorporate 12-hour shifts would have positive effects for
      patients and staff in a ward environment. METHOD: All nurses, night sisters and
      therapists in contact with the ward during the trial were asked to complete a
      questionnaire. Data on sickness, agency use, 'untoward incidents' and spread of
      unsocial hours were also analysed to see what effects a change in shift pattern
      had. RESULTS: The new shift pattern offered benefits for patients through
      improved communication, increased continuity of care and more content staff. In
      addition, staff complied to the Working Time Regulations (DTI 1998) with no
      change to their unsocial hour pay. There was also a reduced need for agency
      nurses. CONCLUSION: This study illustrated the potential a new nursing shift
      pattern involving 12-hour shifts has for patient care, as well as for staff job
      satisfaction and efficient management of the ward. Twelve-hour shifts are
      infamous in nursing and many studies cite exhausted and dissatisfied staff as a
      reason for the negative press (Fitzpatrick et al 1999, Todd et al 1993). In
      particular, Todd et al (1989) claimed that the quality of patient care was
      negatively affected on wards that used a 12-hour shift pattern. The study
      reported here challenges Todd et al's work (1989, 1993) by demonstrating the
      benefits a change in shift pattern to 12-hour shifts can have for patients and
      staff in a ward environment.

PMID- 12216288
TI  - Professional writing: collective purpose.
AB  - Adrienne Price discusses the need for group publication in health care and
      emphasises the importance of developing a publication strategy.

PMID- 12216289
TI  - Hysterectomy.
AB  - Hysterectomy is often thought of as a last resort, but it is a common operation
      and there are many reasons why it is carried out. The author looks at these and
      discusses the different surgical procedures and nursing care for patients
      undergoing hysterectomy.

PMID- 12216290
TI  - Safe and sound.

PMID- 12216291
TI  - Credit where it's due.

PMID- 12216292
TI  - Hospital beat.

PMID- 12216293
TI  - Unique position.

PMID- 12216294
TI  - Lines of thought.

PMID- 12216295
TI  - Define and rule.

PMID- 12216296
TI  - Mother and child reunion.

PMID- 12216297
TI  - The importance of pilot studies.
AB  - The term 'pilot studies' refers to mini versions of a full-scale study (also
      called 'feasibility' studies), as well as the specific pre-testing of a
      particular research instrument such as a questionnaire or interview schedule.
      Pilot studies are a crucial element of a good study design. Conducting a pilot
      study does not guarantee success in the main study, but it does increase the
      likelihood of success. Pilot studies fulfill a range of important functions and
      can provide valuable insights for other researchers. There is a need for more
      discussion among researchers of both the process and outcomes of pilot studies.

PMID- 12216298
TI  - An analysis of an audit tool of ward-based practice.
AB  - This article identifies how, in the current context of clinical governance, an
      audit tool of ward-based practice was developed, piloted and adopted in two acute
      trusts. The content of the tool is briefly outlined together with the process-
      the emphasis being the involvement of staff. This tool is key in assisting nurses
      to value essential aspects of care from the patient's perspective and to
      celebrate or change their practice accordingly.

PMID- 12216299
TI  - Guidance for the psychological care of day case surgery patients.
AB  - An increase in day surgery activity to 75 per cent of all elective surgery is a
      central feature of the NHS Plan (DoH 2000). However, patient information
      provision remains a challenge for all modern surgery as the time spent in
      hospital is brief and the level of self-care has grown. Effective information
      provision and an increased emphasis on psychological care are therefore essential
      to the future of day surgery.

PMID- 12216300
TI  - Nursing care of chronic and acute liver failure.
AB  - The authors describe the structure and functions of the liver, as well as the
      main causes and symptoms of chronic and acute liver failure. The nursing
      assessment and management of patients with liver disease are also examined.

PMID- 12216301
TI  - Life support.

PMID- 12216302
TI  - Minimum effort.

PMID- 12216303
TI  - Limited vision.

PMID- 12216304
TI  - Always on the case.

PMID- 12216305
TI  - Off the record.

PMID- 12216306
TI  - Reality check.

PMID- 12216307
TI  - Breathing space.

PMID- 12216308
TI  - Stiff opposition.

PMID- 12216309
TI  - Medication administration in nursing homes.
AB  - AIM: To describe the difficulties faced when administering oral medication to
      patients with swallowing difficulties in nursing homes, the methods that are used
      to overcome these difficulties and their appropriateness. METHOD: A self
      administered questionnaire was given to all participants (n = 763) at eight
      regional study days for nurses employed in independent nursing homes. The
      questionnaire included sections on respondent and nursing home demographics,
      extent of and methods used to overcome swallowing difficulties, experience of
      overcoming swallowing difficulties and nurses' opinions on the ease of changing
      prescriptions to liquid formulations. RESULTS: Of 763 questionnaires, 540 (70.8
      per cent) were returned completed. On average 15 per cent of all residents had
      difficulty swallowing tablets and capsules, 5 per cent regularly spat out their
      medication and 1 per cent hid it. Hiding medication in food was reported by 56.5
      per cent (n = 305) of respondents, 26.9 per cent (n = 145) omitted the dose, 61.3
      per cent (n = 331) crushed or opened medication before administration and 87.6
      per cent (n = 473) obtained liquid alternatives. Crushing or opening of
      medication (unlicensed administration) took place in more than 80 per cent of all
      nursing homes on at least a weekly basis. The majority of nurses (n = 487, 90.2
      per cent) would not be reluctant to ask the prescriber for a liquid alternative,
      however, 58 per cent (193 out of 333) stated that the prescriber might recommend
      that medicines be crushed or opened, and cost was stated to be a consideration in
      this process by 62 per cent (n = 335) of nurses. CONCLUSION: The crushing or
      opening of medication results in unlicensed administration. Liability lies solely
      with the nurse if the action was unauthorised and is shared with the prescriber
      if it had been authorised. With the availability of most oral medicines as a
      liquid formulation, the majority of reported crushing or opening that is taking
      place is unnecessary. In many instances this is because of prescriber reluctance
      to change the prescription. Nurses choosing to administer medication via a non
      licensed method should ensure that all other avenues have been considered and
      appropriate advice sought. Where unlicensed administration is authorised by the
      prescriber, a written and signed record of this should be obtained.

PMID- 12216310
TI  - Caring for patients with a diagnosis of cancer and spinal metastatic disease.
AB  - This article aims to provide a greater understanding of the process involved in
      diagnosing cancer, particularly that associated with spinal metastasis. The
      article focuses on the diagnosis of secondary cancer of the spine, however, the
      information and discussion might also be relevant to other anatomical areas.

PMID- 12216311
TI  - Subarachnoid haemorrhage: a clinical overview.
AB  - Subarachnoid haemorrhage affects up to 9,000 people a year in the UK (Lindsay and
      Bone 1997) and is a devastating condition. Although many patients make a good
      physical recovery, some are left with cognitive and perceptual deficits. Early
      rehabilitation and support is essential, and caring for these patients and their
      families is a major challenge for nurses.

PMID- 12216312
TI  - Communication is key to HIV drug compliance.

PMID- 12216313
TI  - Driven by fear.

PMID- 12216314
TI  - A need to know.

PMID- 12216315
TI  - Double jeopardy.

PMID- 12216316
TI  - Weighing up the risks.

PMID- 12216317
TI  - Talking my language.

PMID- 12216318
TI  - Non-HIV nurses' knowledge of HIV therapy.
AB  - AIM: To investigate the level of knowledge about HIV among non-specialist nurses.
      METHOD: A purposive sample was taken of 124 students undertaking post
      registration studies in nursing, midwifery and women's health. The instrument
      used was a questionnaire. RESULTS: A response rate of 97.5 per cent was achieved
      (n = 121). The results showed a lack of knowledge among respondents about HIV
      therapy. CONCLUSION: Non-HIV nurses need a sound basic knowledge of HIV therapy
      to deliver safe, effective care to patients. Nurses need access to HIV awareness
      updates at trust level and HIV awareness courses at university level.

PMID- 12216319
TI  - Step-down beds in ENT and maxillofacial surgery.
AB  - The organisation and delivery of critical care services have come under scrutiny
      in recent years with media attention focusing on a shortage of intensive care
      beds and a lack of appropriately trained nurses to staff them (Wright 2000). The
      provision of these services is under review nationally, prompting a new approach
      to the organisation of intensive care and high dependency beds (DoH 2000,
      Scottish Executive 2000). In Lanarkshire in the specialties of ear, nose and
      throat (ENT) and maxillofacial surgery, access to these facilities was restricted
      and not always available or appropriate for these patients' needs. This article
      illustrates how nurses brought about real change by proposing a possible solution
      to establish two step-down beds in the ward. Establishing these beds not only
      provided many benefits for patients, but also gave nurses the opportunity to gain
      advanced skills and ultimately increased job satisfaction.

PMID- 12216320
TI  - A future for critical care education.
AB  - This article discusses the development and implementation of a BSc(Hons)
      programme in critical care practice and the new English National Board D14 award,
      transferable skills in critical care nursing practice (ENB 2000).

PMID- 12216321
TI  - Diet and coronary heart disease.
AB  - Diet is important in the prevention and treatment of coronary heart disease.
      Nurses are key in providing and reinforcing consistent dietary messages as part
      of the multidisciplinary team.

PMID- 12216323
TI  - The roles of insulin and fatty acids in the regulation of hepatic very-low
      density lipoprotein assembly.

PMID- 12216324
TI  - Adipose tissue and fatty acid metabolism in humans.
AB  - It is now clear that there are major regional differences in adipose tissue
      function as regards the uptake and release of fatty acids. Visceral adiposity is
      a good predictor of abnormal regulation of adipose tissue fuel export, but it is
      not the source of excess systemic FFA in humans. Regional differences in adipose
      tissue uptake of fatty acids may be an important determinant of body fat
      distribution, which in turn appears to predict abnormalities of fatty acid
      metabolism.

PMID- 12216322
TI  - Peroxisome proliferator activated receptors, fatty acids and muscle insulin
      resistance.

PMID- 12216325
TI  - Correction of dysfunctional fatty acid metabolism using peroxisome proliferator
      activated receptor gamma agonists.

PMID- 12216326
TI  - Ectopic fat accumulation: an important cause of insulin resistance in humans.

PMID- 12216327
TI  - Metabolic pathogenesis of familial combined hyperlipidaemia with emphasis on
      insulin resistance, adipose tissue metabolism and free fatty acids.

PMID- 12216329
TI  - Cellular mechanism of insulin resistance in skeletal muscle.

PMID- 12216330
TI  - While Congress fiddles, Supreme Court gives thumbs up to external review.

PMID- 12216332
TI  - Gridiron G.P.S. Friday night physicians keep the game going.

PMID- 12216331
TI  - Sugar, spice and some herbal remedies that aren't so nice.

PMID- 12216328
TI  - Insulin resistance and vessel endothelial function.
AB  - IRS is a complex disease consisting of a clustering of metabolic disorders, of
      which hyperglycaemia, hyper-insulinaemia and dyslipidaemia are the most
      important. Endothelial dysfunction plays an important role in the pathogenesis of
      atherosclerosis. The effects of hyperinsulinaemia seem to depend on lipidaemia
      and glycaemia. Hyperglycaemia and hyperlipidaemia have detrimental effects on
      endothelial function in the fasting as well as the postprandial states. In both
      situations, the generation of ROS and vasoactive molecules plays a major role in
      interfering with the atheroprotective endothelium-dependent NO system. Treatment
      of IRS in regard to endothelial function should be focused initially on lifestyle
      improvement, such as stopping smoking and eating a balanced diet containing
      antioxidant vitamins, folic-acid, L-arginine and long-chain omega-3 unsaturated
      FA. Strict glucose control has shown to improve endothelial function and decrease
      microvascular complications. However, macrovascular complications, in line with
      endothelial functional improvement, have so far been reduced only when treatment
      was focused on other characteristics of the IRS syndrome, in particular
      dyslipidaemia. Other relevant treatments include ACE inhibitors and
      thiazolidinediones, and probably tetrahydrobiopterin and folic acid
      supplementation. Future studies should address the effects of therapeutic
      neovascularization on endothelial dysfunction.

PMID- 12216333
TI  - The disaster of a suspected cover-up.

PMID- 12216334
TI  - Asthma treatment in Arkansas: improved use of anti-inflammatory drugs benefits
      patients.

PMID- 12216335
TI  - Cutaneous myiasis in Arkansas.
AB  - Myiasis is a rare infestation of any part of the body by larvae of Diptera.
      Cutaneous myiasis, the most common form seen in tropical climates of Central
      America, South America and Africa, are extremely rare in the United States. An
      extraordinary case of cutaneous myiasis was seen in Hot Springs in a 71-year-old
      healthy white male upon his return from the rain forest of Costa Rica. Manual
      extraction of one of the larvae by the patient and surgical excision of three
      other separate subcutaneous larvae were diagnostic and therapeutic in this case.

PMID- 12216336
TI  - Management of common disorders of the inguinal canal and scrotum in childhood and
      adolescence.
AB  - Primary care physicians, including family practitioners and pediatricians,
      frequently are consulted about children and adolescents with disorders of the
      inguinal canal and scrotum and are asked about the proper course of management,
      even if only to confirm an opinion of the surgical specialist. The purpose of
      this communication is to review the management of these conditions, including
      undescended testis, hydrocele and hernia, varicocele, testicular torsion,
      testicular trauma, epididymo-orchitis and scrotal edema.

PMID- 12216337
TI  - Is [symbol: see text] Yasmin a "truly different" pill?
AB  - A combined oral contraceptive (COC) containing the progestogen drospirenone
      (pronounced dro-spi-re-known) plus the oestrogen ethinylestradiol ([symbol: see
      text] Yasmin--Schering Health Care) is now available in the UK. Company
      advertising claims that Yasmin is "truly different", as reliable and safe as
      other COCs and is "the pill for well-being", with "no associated weight gain" and
      "a demonstrable positive effect" on premenstrual symptoms and skin condition.
      Such claims have also appeared in the lay media. Are they justified?

PMID- 12216338
TI  - Oral antihistamines for allergic disorders.
AB  - There are now 17 oral H1-antihistamines available in the UK for treating allergic
      disorders. Here, we assess their use in treating hayfever, urticaria and
      pruritus, and consider whether any hold particular advantages.

PMID- 12216339
TI  - [symbol: see text] Seretide and [symbol: see text] Symbicort in asthma
      management.
AB  - Maintenance treatment for mild asthma frequently comprises both a regular inhaled
      corticosteroid and an 'as required' inhaled short-acting beta 2-agonist. Where
      such treatment fails, additional regular treatment with an inhaled long-acting
      beta 2-agonist is increasingly recommended. In the UK, combination inhalers
      containing salmeterol + fluticasone ([symbol: see text] Seretide--Allen &
      Hanburys) or formoterol + budesonide ([symbol: see text] Symbicort--AstraZeneca)
      are licensed for use either in "patients not adequately controlled with inhaled
      corticosteroids and 'as needed' inhaled short-acting beta 2-agonists" or in
      "patients already adequately controlled on both inhaled corticosteroids and long
      acting beta 2-agonists". Here we review the efficacy of Seretide and Symbicort
      and discuss their place in asthma management.

PMID- 12216340
TI  - Watch your feet! Crushing hazard with movable foot controls and adjustable tables
      and chairs.

PMID- 12216341
TI  - Issues surrounding blood pressure measurements.

PMID- 12216342
TI  - Inadvertent deactivation of NIBP auto mode on the invivo magnitude 3150 pedestal
      monitor.

PMID- 12216343
TI  - Microsystems in health care: Part 1. Learning from high-performing front-line
      clinical units.
AB  - BACKGROUND: Clinical microsystems are the small, functional, front-line units
      that provide most health care to most people. They are the essential building
      blocks of larger organizations and of the health system. They are the place where
      patients and providers meet. The quality and value of care produced by a large
      health system can be no better than the services generated by the small systems
      of which it is composed. METHODS: A wide net was cast to identify and study a
      sampling of the best-quality, best-value small clinical units in North America.
      Twenty microsystems, representing different component parts of the health system,
      were examined from December 2000 through June 2001, using qualitative methods
      supplemented by medical record and finance reviews. RESULTS: The study of the 20
      high-performing sites generated many best practice ideas (processes and methods)
      that microsystems use to accomplish their goals. Nine success characteristics
      were related to high performance: leadership, culture, macro-organizational
      support of microsystems, patient focus, staff focus, interdependence of care
      team, information and information technology, process improvement, and
      performance patterns. These success factors were interrelated and together
      contributed to the microsystem's ability to provide superior, cost-effective care
      and at the same time create a positive and attractive working environment.
      CONCLUSIONS: A seamless, patient-centered, high-quality, safe, and efficient
      health system cannot be realized without the transformation of the essential
      building blocks that combine to form the care continuum.

PMID- 12216344
TI  - Microsystems as practical neopragmatism and "strong poetry": comments from the
      microsystem series editor--and microsystem student.

PMID- 12216345
TI  - Microsystem management as a promising new methodology for improving the cost and
      quality of health care.

PMID- 12216346
TI  - Senior leaders' role in improving the performance of the front-line delivery
      units.

PMID- 12216347
TI  - A rapid interview protocol supporting patient-centered quality improvement:
      hearing the parent's voice in a pediatric cancer unit.
AB  - BACKGROUND: The Institute of Medicine's 2001 report on quality delimits six
      dimensions of optimal care: safety, effectiveness, efficiency, timeliness,
      patient centeredness, and equity. In fall 2001 parents of pediatric cancer
      patients were interviewed to determine how well they thought these dimensions
      were addressed with respect to medication administration. Immediate goals were to
      identify system weaknesses and devise strategies to prevent future errors. A
      higher-order goal was to develop and demonstrate a model protocol for rapid-cycle
      interview assessments. METHODS: Hematology/oncology directors worked with a
      research expert to develop a semistructured interview protocol. After training,
      which included directed reading, oral instruction, and role-playing, a
      convenience sample of 20 English- and Spanish-speaking parents of inpatients was
      recruited. Parents were asked to characterize current medication administration
      practices and to describe problems that they had experienced or witnessed. Rapid
      content analysis techniques were used to identify issues of importance to the
      parents. FINDINGS: Parents' medication concerns centered on their children's
      comfort. Parents called for communication improvements, standardization of all
      nursing procedures and techniques, and a guide or an outline providing a clear
      understanding of what to expect when and from whom. Viewing these concerns in
      relation to the Institute of Medicine's quality domains allowed the department to
      frame an improvement action plan aligned with organizational and national
      priorities. IMPLICATIONS: With good supervision and limited focused training,
      inexperienced staff can successfully administer semistructured qualitative
      interviews and help analyze findings for rapid cycle improvement purposes. The
      protocol can be adapted for use in organizations interested in rapid qualitative
      assessments of patient and parent preferences.

PMID- 12216348
TI  - Assessing consumer perceptions of inpatient psychiatric treatment: the
      perceptions of care survey.
AB  - BACKGROUND: Consumer perceptions of behavioral health care are widely recognized
      as important quality indicators. This article reports the development and use of
      the Perceptions of Care (PoC) survey, a standardized public domain measure of
      consumer perceptions of the quality of inpatient mental health or substance abuse
      care. The goals were to develop a low-cost, low-burden survey that would address
      important quality domains, allow for interprogram comparisons and national
      benchmarks, be useful for quality improvement purposes, and meet accreditation
      and payer requirements. METHODS: The sample was composed of 6,972 patients
      treated in 14 inpatient behavioral health or substance abuse treatment programs.
      The PoC survey was given to patients by program staff in the 24-hour period
      before discharge. RESULTS: Aggregate reports and ratings of care identified areas
      that are highly evaluated by consumers, as well as areas that provide
      opportunities for quality improvement. Factor analysis identified four domains of
      care, and a 100-point score was developed for each domain. Regression analyses
      identified significant predictors of perceptions of care for use in computing
      risk-adjusted scores. Unadjusted and adjusted scores were presented to
      demonstrate the impact of risk adjustment on quality of care scores and relative
      ranking of programs. Examples were given of how programs used survey results to
      improve the quality of care. DISCUSSION: Results demonstrated that the PoC survey
      is sensitive to detecting differences among inpatient behavioral health programs
      and can be useful in guiding quality improvement efforts. However, risk
      adjustment is important for appropriate interpretation of results.

PMID- 12216349
TI  - Reassessing cancer mortality in Rhode Island, an old urban state.

PMID- 12216350
TI  - Recent developments in aged care policy in Australia.
AB  - A series of major reforms implemented through the mid 1980s sought to contain
      residential care and expand community care in Australia's long-term care system.
      While this goal has been maintained, a number of new policy initiatives followed
      the change of federal government in 1996. This article presents a systematic
      account of current policy objectives, implementation measures, and outcomes in
      three major policy areas: changing the balance between residential and community
      care, targeting in community care, and support for family caregivers. This
      analysis shows that while there have been shifts in emphasis from time to time,
      concerted policy efforts over the last 20 years have contained the growth of
      expenditure on long-term care and realized significant change in the service
      system.

PMID- 12216351
TI  - Australian approaches to resident classification and quality assurance in
      residential care.
AB  - This paper begins with an account of the structure of Australia's residential
      long-term care program, which was divided into two distinct levels of hostel and
      nursing home care until 1997. In response to changed policy objectives, a number
      of measures were then taken to create an integrated residential care system. The
      main measures were the development of a single scale for classification of
      resident care need and associated funding to replace two previous separate
      scales, and the implementation of a new quality assurance system, which included
      new standards for buildings as well as revised standards for care. I give
      accounts of these measures and the extent to which they have achieved their
      intended outcomes before proposing some further developments that could see
      closer links among pre-admission assessment, resident classification, and quality
      assurance.

PMID- 12216352
TI  - Long-term care policy for elders in Hong Kong.
AB  - The context in which aged care policy is being developed in Hong Kong is
      characterized not only by rapid demographic aging and social change, but also by
      new political and administrative systems being built on a colonial legacy. This
      article begins with a description of the demographic profile and trends in
      population aging, noting particular differences in marriage and family formation
      that differentiate Hong Kong from other developed countries and that also show
      marked changes between generations. While past social policies can be credited
      with contributing to the achievement of high life expectancy in Hong Kong, these
      policies were unevenly developed, with little provision for income security in
      old age or for long-term care. Both issues have come to the fore in policy
      development in recent years, culminating in the formation of the Elderly
      Commission in 1997 and revitalizing the level of attention given to developing
      community care. A clear policy agenda has been drawn up to promote the
      development of a long-term care system, addressing issues of integration; role
      differentiation for assessment and service provision, including new contractual
      arrangements; quality assurance; and financing. The political and administrative
      changes are seen to present opportunities for containing residential care and
      forging a care system founded on community services.

PMID- 12216353
TI  - Changing needs and changing service delivery for long-term care in Hong Kong.
AB  - Both the need for and delivery of long-term care in Hong Kong are shaped by the
      interaction of the traditional and modern. Rapid social change is affecting
      traditional family structures and roles in care of the elderly, resulting in
      increased demand for formal care, which to date has been provided mainly by way
      of residential care. This growth of demand will escalate with rapid population
      aging in coming decades. In response to this burgeoning demand, current planning
      is seeking to reshape the established service system and tackle problems in
      service delivery in ways that will address the bias towards residential care and
      improve quality of care.

PMID- 12216354
TI  - The savings approach to financing long-term care in Singapore.
AB  - Singapore is grappling with provision of services for the current generation of
      older people at the same time as building the foundation for the coming
      generations of elderly. In this article, I analyze four sets of factors that are
      shaping long-term care policy and financing in ways that are almost unique to
      Singapore. First, current developments can only be understood in the context of
      the Central Provident Fund (CPF) that was established by the Government of
      Singapore in the 1950s to ensure that the working population saved for
      retirement; the Medisave and related schemes for financing health care were
      subsequently developed alongside the CPF. Most recently, the existing funding
      arrangements have been extended to some long-term care services, and options for
      further extensions are under consideration. Second, the government's philosophy
      of maintaining the primacy of family support for the elderly has been expressed
      through a number of initiatives that provide financial and other incentives to
      families, combined with an emphasis on community care. The third factor is the
      relationship between government and the voluntary welfare organizations that are
      the major providers of institutional and community services. Finally, a series of
      government-sponsored reviews and advisory councils have provided for widespread
      consultation on policy options. These developments are directed to achieving a
      multi-pillar approach in which intergenerational transfers through taxation will
      be limited, and the role of individual savings and insurance will be increased.

PMID- 12216355
TI  - Organization and delivery of long-term care in Singapore: present issues and
      future challenges.
AB  - This paper focuses on the Singaporean model of long-term care for older people.
      With only about 2% of the older population living in institutions, the mainstay
      of long-term care is community care. The reader is provided an overview of the
      Singaporean services, including case management, followed by a discussion of the
      current issues and future challenges. In keeping with the prospect of a rapidly
      aging population profile, the Singapore government plays a leading role in
      framing policy and planning for future needs of this sector of the population.

PMID- 12216356
TI  - Exploring policy and financing options for long-term care in Taiwan.
AB  - Policy and financing arrangements for long-term care are important themes in each
      country and/or region, and Taiwan, with its unique historic and politico-economic
      background, can be regarded as a bridge between well-developed and under
      developed countries. Policy formulation about long-term care in Taiwan involves
      several agencies in the government, including Ministry of Health, Interior
      Affairs, Education, Insurance Bureau, and Economic Council, and formulation of
      policy objectives has progressed considerably in the last five years. Financing
      arrangements are less well-developed because the National Health Insurance
      Program began only in 1995, and most long-term care is not yet covered. As demand
      for long-term care exceeds supply, and this gap will grow in future, current
      resource allocation measures are concerned to facilitate the expansion of
      community care rather than allowing institutional care to absorb more resources.
      Developing future financing options is now a central task for policymaking, and
      government must continue to take a leading role in consolidating financial and
      integrating the service systems.

PMID- 12216357
TI  - Aged care service delivery in Japan: preparing for the long-term care insurance
      scheme.
AB  - The implementation of Japan's Long-Term Care Insurance Scheme in early 2000
      presaged many changes in service delivery and much debate among service
      providers, different levels of government, academic analysts, and major media
      interests. The first part of this paper gives an account of the major changes in
      the organization of service delivery that have increased opportunities for
      private sector providers, including large corporations, and restructured
      contractual relationships between municipalities and providers in all sectors.
      New arrangements for client assessment, classification, care management, and
      extended service types are then outlined. An assessment is then made of the
      likelihood that the expected outcomes of the scheme will be realized, with the
      concerns of welfare professionals that the public welfare system is under threat
      juxtaposed with bureaucratic goals of liberalizing the provision of long-term.

PMID- 12216359
TI  - Lessons learned, questions raised.

PMID- 12216358
TI  - Organization and delivery of long-term care in Taiwan.
AB  - Taiwan reached the World Health Organization (WHO) benchmark of 7% aged 65 and
      over for defining an aging population only as recently as 1993. With this
      proportion projected to double to 14% by 2020, Taiwan faces a rapid increase in
      need for long-term care. This article presents an account of the current service
      delivery system, which is divided between health and social affairs
      administrations, with a substantial role also taken by the Veteran
      Administration, and growing provision of facilities that operate outside the
      government-registered system. While a basic level of both institutional and
      community care services has developed, they are not organized into an integrated
      service system. Problems arising from the divisions and overlaps in
      responsibility are identified in relation to competition for resources,
      differences in regulation and eligibility, funding arrangements and misallocation
      of resources, and divergent views about the philosophical basis of long-term
      care. Other aspects of services fall under each jurisdiction, but there is also
      some overlap. A case study of Taiwan's second largest city, Kaohsiung City,
      reports the outcomes of these divisions as a thin spread of a range of services
      rather than a coordinated service network. Several planning exercises have been
      undertaken in recent years to address these problems, and although at an early
      stage of implementation, the outcomes of these plans are seen as shaping the
      future directions of long-term care in Taiwan.

PMID- 12216360
TI  - Long-term care policy and financing as a public or private matter in the United
      States.
AB  - Effective approaches to assure adequate resources, infrastructure, and broad
      societal support to address chronic care needs are volatile and potentially
      unpopular issues that can result in many losers (those getting far less than they
      want) and few winners (those who gain access to scarce societal resources for
      care). In the United States, debates on long-term care involve a complex set of
      issues and services that link health, social services (welfare), and economic
      policies that often pit public and private sector interests and values against
      one another. Yet long-term care policies fill a necessary function in society to
      clarify roles, expectations, and functions of public, non-profit, for profit,
      individual, and family sectors of a society. By assessing and developing policy
      proposals that include all long-term care system dimensions, a society can arrive
      at systematic, fair, and rational decisions. Limiting decisions to system
      financing aspects alone is likely to result in unforeseen or unintended effects
      in a long-term care system that stopgap "fixes" cannot resolve. Three underlying
      policy challenges are presented: the need for policymakers to consider whether
      the public sector is the first or last source of payment for long-term care;
      whether government is seen primarily as a risk or cost manager; and the extent to
      which choice is afforded to elders and family caregivers with regard to the
      types, settings, and amount of long-term care desired to complement family care.

PMID- 12216361
TI  - Long-term care policy reform in Japan.
AB  - The implementation of Japan's Long-Term Care Insurance Scheme in April 2000 was
      the culmination of some 30 years of policy deliberation on aged care.
      Understanding the policy debate surrounding the Long-Term Care Insurance scheme
      and its financing arrangements requires an appreciation of rapid demographic and
      social change, especially in family structures and attitudes to caring for aged
      parents; but the pressures that population aging and economic downturn are
      placing on Japan's pension and health insurance systems also must be recognized.
      Even more generally, the delicate balance of political interests in Japan's
      central governing body, the Diet, has shaped the implementation of Long-Term Care
      Insurance as a forerunner to other reforms in social security and health
      insurance.

PMID- 12216363
TI  - Long-term care funding in Canada: a policy mosaic.
AB  - When Canada was founded, health care was delegated as a provincial
      responsibility. Although the federal government shares a portion of health care
      costs, it is not directly responsible for the planning, delivery, and governance
      of health services. The 1984 Canada Health Act set national standards for the
      provision of physician and hospital services, but it does not apply to home care
      and long-term care facilities. Consequently, each province has established a
      unique approach to long-term care, resulting in a health policy mosaic. This
      paper examines different approaches to funding long-term care with a particular
      emphasis on the impacts of regionalization and of the implementation of case-mix
      based funding systems.

PMID- 12216362
TI  - The Program of All-Inclusive Care for the Elderly (PACE): an innovative long-term
      care model in the United States.
AB  - This article examines the long-term care service system in the United States, its
      problems, and an improved long-term care model. Problematic quality of care in
      institutional settings and fragmentation of service coordination in community
      based settings are two major issues in the traditional long-term care system. The
      Program of All-Inclusive Care for the Elderly (PACE) has been emerging since the
      1970s to address these issues, particularly because most frail elders prefer
      community-based to institutional care. The Balanced Budget Act of 1997 made PACE
      a permanent provider type under Medicare and granted states the option of paying
      a capitation rate for PACE services under Medicaid. The PACE model is a managed
      long-term care system that provides frail elders alternatives to nursing home
      life. The PACE program's primary goals are to maximize each frail elderly
      participant's autonomy and continued community residence, and to provide quality
      care at a lower cost than Medicare, Medicaid, and private-pay participants, who
      pay in the traditional fee-for-service system. In exchange for Medicare and
      Medicaid fixed monthly payments for each participating frail elder, PACE service
      systems provide a continuum of long-term care services, including hospital and
      nursing home care, and bear full financial risk. Integration of acute and long
      term care services in the PACE model allows care of frail elders with multiple
      problems by a single service organization that can provide a full range of
      services. PACE's range of services and organizational features are discussed.

PMID- 12216364
TI  - National consistency and provincial diversity in delivery of long-term care in
      Canada.
AB  - The aim of this article is to demonstrate the diversity in delivery of long-term
      care at the provincial level, within a national legislative framework that
      provides universal health insurance and public administration. Not all provinces
      have legislated provision of long-term care, but mandates for provincial long
      term care programs typically address the needs of those with chronic health needs
      and maintain them in the community for as long as possible. Eligibility is based
      on common criteria of residency, health need, facility, assessment, and consent.
      The three common components of the service delivery system are institutional
      care, community-based services, and home-based services; the kinds of services
      within each component and the mix among them vary from province to province.
      There are also five common features in provincial service delivery systems:
      single point of entry, assessment, client classification, case management, and
      single administration. Throughout the article, examples from different provinces
      show the varying ways in which these aspects of service delivery have been
      addressed, and recent innovations have furthered this diversity. A detailed
      account of quality management systems also shows that while all provinces have
      adopted a common set of principles, they use a range of methods to pursue quality
      of care and to promote good practice.

PMID- 12216365
TI  - A great IDEA!

PMID- 12216366
TI  - The primary therapist model: addressing challenges to practice in special
      education.
AB  - When occupational therapy (OT) and physical therapy (PT) are provided as related
      services in educational settings, federal law, professional guidelines, and
      validated practices have pointed to appropriate models of service provision.
      Issues such as personnel shortages, professional isolation, and questionable
      educational relevance of services all create barriers to use of recommended
      practices. The overlap between OT and PT in special education suggests one
      strategy to help address these barriers: a primary therapist model. In this
      model, an OT or PT is assigned as primary therapist, with consultation from the
      other discipline as required to meet student needs. Potential benefits of the
      model, challenges in implementation, the best practice framework needed to
      support the model, and the need for research on costs and benefits are discussed.

PMID- 12216367
TI  - A life needs model of pediatric service delivery: services to support community
      participation and quality of life for children and youth with disabilities.
AB  - This article presents a life needs model of pediatric service delivery that is
      based on the values of the intrinsic worth, dignity, and strengths of
      individuals. This developmental, socio-ecological model outlines the major types
      of service delivery needs of children and youth with disabilities, their
      families, and their communities within three spheres of life (the personal,
      interpersonal, and external spheres). The model legitimizes the concept of need,
      emphasizes the values of family-centered services, and recognizes child and
      family strengths and capacities. We discuss the utility of this transdisciplinary
      model in guiding pediatric service delivery to meet the long-range goals of
      community participation and quality of life of children and youth with
      disabilities.

PMID- 12216368
TI  - Construct validity of the Miller assessment for preschoolers and the pediatric
      examination of educational readiness for children.
AB  - The purpose of this study was to investigate the construct validity of the Miller
      Assessment for Preschoolers (MAP) and the Pediatric Examination of Educational
      Readiness (PEER), two assessment tools that occupational therapists and physical
      therapists can use for early identification of children with developmental
      disabilities. The sample included 84 Israeli children who were tested on the MAP
      (42 children with pre-academic problems and 42 typically developing children),
      and 70 children who were tested on the PEER (35 children with pre-academic
      problems and 35 typically developing children). Out of this pool of subjects, 30
      typically developing children and 30 children with pre-academic problems were
      tested on both tests and the results were used for additional data analysis. We
      found differences between the groups' MAP and PEER total scores as well as their
      developmental indices scores. Children with pre-academic problems scored lower.
      The supplementary behavioral observations of the tests yielded less definite
      results. A strong correlation existed between the total scores of the MAP and the
      PEER, and the total scores of the tests correlated significantly with each of the
      sub-scores of the other test. The findings support the construct validity of both
      tests, thereby suggesting that either test can be used to identify children with
      pre-academic problems.

PMID- 12216369
TI  - Review of the reliability and validity of myometry with children.
AB  - Pediatric occupational therapists and physical therapists often measure muscle
      strength, and muscle strength frequently is cited as an indicator of function in
      clinical practice and in research. A reliable measure to quantify strength is
      necessary to accurately assess muscle strength so the values can be used for
      comparison, study, and indication of change. The hand-held myometer provides an
      alternative to traditional methods of manual muscle testing, and its reliability
      and validity have been examined in adults. The purpose of this review is to
      summarize the available literature relating to the reliability and validity of
      the hand-held myometer when used with children and to identify directions for
      future study in the use of myometers with children.

PMID- 12216370
TI  - Preventive mental health and substance abuse programs and services in managed
      care.
AB  - If effective preventive behavioral health services were available to the millions
      of Americans enrolled in managed care organizations, the public health impact
      could be significant. This project sought to summarize published research-based
      information about effective preventive interventions for mental health and
      substance use (tobacco, alcohol, and other drugs) shown or likely to have no
      negative cost impact. Fifty-four studies satisfied seven screening criteria.
      Their findings demonstrated that preventive behavioral health interventions
      appropriate for managed care settings have been evaluated and have been shown to
      be effective. Some produced cost savings or offset costs. Six preventive
      behavioral health interventions are therefore recommended for managed care.

PMID- 12216371
TI  - Assessing the effectiveness of care for youth with severe emotional disturbances:
      is there agreement between popular outcome measures?
AB  - Limited information exists regarding how some popular measures for assessing the
      effectiveness of services to children with severe emotional disturbance
      interrelate when used as part of ongoing outcome accountability systems. This
      article examines the interrelationships--at intake and over time--between the
      Child Behavior Checklist (CBCL), the Youth Self Report (YSR), the Child and
      Adolescent Functional Assessment Scale (CAFAS), and Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition (DSM-IV) clinical diagnoses across six
      California care systems. At intake, there were mild to moderate relationships
      between the clinical diagnosis, the CAFAS, the CBCL, and the YSR. These
      relationships were not as strong as those found in other studies conducted in
      more controlled research environments. There was limited agreement among the
      CAFAS, the CBCL, and the YSR regarding the outcomes of the youths served. These
      findings raise questions regarding translating measures from research settings to
      clinical environments and reconciling differences between outcome measures.

PMID- 12216372
TI  - Clinicians as advocates: an exploratory study of responses to managed care by
      mental health professionals.
AB  - Utilization review and other managed care techniques require that health care
      professionals assume new responsibilities as patient advocates. This article
      explores the extent to which characteristics of providers or their experiences
      with managed care practices predict the nature and extent of advocacy behavior.
      Interviews of 142 mental health providers revealed that experiences of harmful
      utilization review and norms of professionalism significantly predicted advocacy
      behavior. However, providers who were concerned about disaffiliation were less
      likely to challenge the plan directly but more likely to alter their presentation
      of the case to reviewers. Providers who believe that managed care plans retaliate
      against advocacy behavior appear to substitute covert advocacy for direct
      advocacy. These results are preliminary but suggest that providers condition
      their advocacy behavior in response to their experiences with and perceptions of
      managed care plans.

PMID- 12216373
TI  - A brief telephone intervention targeting treatment engagement from a substance
      abuse program wait list.
AB  - This study compares three brief participant-initiated telephone interventions
      aimed at enhancing treatment engagement of individuals on a substance abuse
      treatment wait list. Policies requiring that wait list members call at least
      every other week in order to remain eligible for treatment remained in place for
      the standard and enhanced conditions but not for the voluntary condition. The
      standard condition was a minimal intervention, providing information on the
      program. The enhanced condition focused on client motivation for treatment and
      recovery. If individuals in the voluntary condition called, they were provided
      information about current wait list number and approximate remaining wait time.
      The rate of treatment engagement was the same among treatment conditions. The
      best predictor of engagement was the number of calls placed to the program while
      waiting. Treatment condition was a positive predictor of call frequency; presence
      of a comorbid psychiatric diagnosis was a negative predictor. The article also
      discusses future directions.

PMID- 12216374
TI  - State mental hospitals and their host communities: the origins of hostile public
      reactions.
AB  - This article examines the hostile public reactions of a community that, through a
      state policy to consolidate all long-term behavioral health services, was to
      become the site of the state's only mental hospital. A telephone survey conducted
      in the host community (n = 800) and a matched community (n = 800) was used to
      test whether the origins of hostility toward consolidation were related to the
      public's negative attitudes toward mental illness and homelessness or to the
      beliefs about the discharge and supervisory behavior of the hospital. The host
      community was not found to have more negative views of mental illness, although
      it did have significantly more negative views about the homeless. Disapproval of
      consolidation was unrelated to negative views of mental illness or homelessness
      but was strongly related to the expected "bad" behavior of the hospital. These
      results suggest that the best way to improve relations between hospitals and
      their host communities is for hospitals to behave like "good" neighbors.

PMID- 12216375
TI  - Theoretical basis and program design of a school-based mental health intervention
      for traumatized immigrant children: a collaborative research partnership.
AB  - This article describes a collaborative research model for school-based mental
      health services that targets children who are recent immigrants with violence
      related mental health symptoms. The model describes a conceptual framework used
      in the establishment of an academic-community partnership during the development,
      evaluation, and implementation of the Mental Health for Immigrants Program
      (MHIP), a school-based mental health intervention. The article discusses the
      challenges that occurred and provides specific examples of how a participatory
      research partnership may work together through all program phases--design through
      implementation and program evaluation--to meet a specific community's needs and
      produce generalizable knowledge. The challenges and limitations of collaborative
      research approaches also are discussed, with particular emphasis on the role of
      participatory research in the development and evaluation of school-based mental
      health programs.

PMID- 12216376
TI  - Clients with substance abuse and mental health concerns: a guide for conducting
      intake interviews.
AB  - Although comorbidity (co-occurrence of a psychiatric and substance use disorder)
      is a common phenomenon at both mental health and substance abuse treatment
      agencies, rarely do such agencies thoroughly assess for both types of diagnoses
      during their standard intake interview. This article describes the development of
      an intake form designed to guide a comprehensive assessment of both mental health
      and substance abuse concerns. The form guides intake interviewers toward
      documenting administrative and demographic information, substance use and mental
      health concerns, and variables needed for compliance with grant funding sources.
      Use of the protocol and provide a clinical foundation for treatment planning and
      continuity of care for clients, while also providing error-free agency data that
      can be used for administrative, program planning, outcome assessment, and
      research purposes.

PMID- 12216377
TI  - The mental health care context and patient characteristics: implications for
      provider job satisfaction.
AB  - This research examines job satisfaction among 282 staff providing mental health
      care to 574 patients with serious mental illness. The mental health staff worked
      in 18 Department of Veterans Affairs inpatient and outpatient mental health care
      units at 12 Veterans Affairs Medical Centers located across the contiguous 48
      states. The purpose was to identify (1) aspects of the health care context that
      were associated with provider job satisfaction and (2) administrative and
      organizational procedures/interventions that might sustain or improve provider
      job satisfaction. The association of provider job satisfaction with patients'
      functional status and symptom severity was tested in multilevel statistical
      models that accounted for provider and unit characteristics. Provider job
      satisfaction was found to be greater on smaller units and units with higher
      patient functioning and lower illness severity. Implications of these results are
      discussed.

PMID- 12216378
TI  - The relationship between problem severity and ancillary treatment services: is
      substance abuse treatment responsive to client need?
AB  - This study examined whether a greater self-reported problem severity at intake is
      associated with a greater likelihood of receiving related ancillary treatment
      services. The sample of 3,625 adult substance abuse treatment completers
      represents 162 outpatient and 41 short-term inpatient/residential programs
      located throughout Minnesota. Problem severity and receipt of ancillary services
      were assessed in medical, psychological, family/social, employment, financial,
      and legal domains. Across treatment setting and client gender, individuals with
      higher problem severity were significantly more likely to receive related
      ancillary services in the areas of medical services, psychotropic medication,
      family/relationship counseling, financial services, and legal services. For other
      services, the positive association between problem severity and receipt of
      related ancillary services held for some but not all groups defined by treatment
      setting or gender. Despite consistent relationships between service need and
      receipt, large gaps remain with respect to programs' responsiveness to client
      needs.

PMID- 12216379
TI  - Special olympics, special athletes, special needs?
AB  - Based upon the current study, the review of the literature, and our experience,
      the preparticipation physical examination for Special Olympics is an opportunity
      for physicians of all specialties to assist and encourage a group of athletes
      with special physical and emotional characteristics not found in other athletes.
      The physician should review the medical condition of the athlete (including
      prescribed medications and their potential side effects), the physical demands of
      the proposed activity, and the presence of volunteers to assist the athlete when
      necessary. Full or limited participation should be recommended in most cases. "No
      participation" should only apply to unstable medical conditions or situations
      that would place the athlete at risk for injury despite activity modification and
      close supervision.

PMID- 12216380
TI  - Tyramine induced hypertensive episodes and panic attacks in hereditary deficient
      monoamine oxidase patients: case reports.

PMID- 12216381
TI  - Recurrent bacterial meningitis: the search for a cause.

PMID- 12216382
TI  - Medicinal treatment of intractable dyspnea in terminally ill patients.

PMID- 12216383
TI  - Palliative care for the terminally ill.

PMID- 12216384
TI  - [Minimum sampling area and species richness of riparian community in erdaobaihe
      forested watershed].
AB  - Riparian zone is an important component of small forested watershed. Due to the
      integrate effects of stream water and edge effect, there are obvious difference
      in composition, structure, and distribution pattern between riparian community
      and non-riparian community. Community minimum sampling areas are also different.
      In this study, minimum sampling areas of riparian community in original broad
      leaved and Korean pine forest in Changbai Mountain were studied by using species
      area curve. At the same time, species richness of riparian community was
      discussed. The results showed that the minimum sampling areas of riparian plant
      community were smaller than those of the non-riparian community. According to the
      original broad-leaved and Korean pine forest in Changbai Mountain, the average
      community minimum sampling areas in riparian zone of three plots including 60%,
      80%, and 90% of community species were about 80 m2, 180 m2, and 320 m2,
      respectively. And then, those of forest community were about 260 m2, 380 m2, and
      480 m2 correspondingly. The results also showed that the species richness of
      riparian community was higher than that of non-riparian community.

PMID- 12216385
TI  - [Effect of elevated atmospheric CO2 concentrations on photosynthesis light
      response characteristics of three coniferous tree species seedlings].
AB  - Potted seedlings of Pinus koraiensis, Picea koraiensis, and Larix olgensis, the
      dominant coniferous tree species in Changbai Mountain, were grown under elevated
      CO2 concentration (700 mumol.mol-1) and ambient CO2 concentration (400 mumol.mol
      1) for two year, and their photosynthesis light response curves were determined
      with CI-301PS CO2 gas analysis system under a series of light intensity from 0 to
      2500 mumol.quanta.m-2.s-1. The comparison of dark respiration rate (DRR), maximum
      net photosynthetic rate (Amax), quantum use efficiency (QUE), light compensation
      point (LCP), light saturation point (LSP) and photo inhibition point (PP) for the
      seedlings of these coniferous tree species under different CO2 concentration
      showed that Larix olgensis, which had better adaptation of photosynthesis to
      elevated CO2 concentration, was heliophilous species. The shade-tolerant species
      Picea koraiensis showed the least adaptation of photosynthesis to elevated CO2
      concentration. Furthermore, the relationship between photosynthetic physiological
      character of tree species and their succession status was also discussed in this
      paper.

PMID- 12216386
TI  - [Improvement and application of digitized measure on shelterbelt porosity].
AB  - Based on the lots of investigation on farmland shelterbelts, we used digital
      camera to take pictures of shelterbelt and apply CIAS software to improve
      "digital image processing" for determining shelterbelt porosity so as to
      thoroughly analyze the rule of porosity in farmland shelterbelts. Compared with
      the old digital image processing, the improved method possesses high accuracy,
      and it is more economical and more convenient to apply. The relationship between
      porosity of shelterbelts (beta) and relative clear bole height (x) can be
      expressed as beta = 0.672x0.469 (r = 0.9851, r0.01 = 0.4073, 0 < or = beta < or =
      1) in the leaf period; and beta = 1.0681x0.4304 (r = 0.9763, r0.01 = 0.4073, 0 <
      or = beta < or = 1) in the defoliation period. beta varies with the stand age
      (a), taking the form of parabola, which can be expressed as beta = 0.0009a2 -
      0.0364a + 0.6828 (0 < or = beta < or = 1). Porosity at cross-section of
      shelterbelt can be used as an auxiliary index to evaluate the structure of belts.
      The calculation method of shelterbelt porosity of mixed shelterbelt can be
      expressed as beta = (beta 1n1 + beta 2n2)/(n1 + n2). Among the popular, willow
      and elm pure shelterbelts with same disposition, popular shelterbelt structure is
      the best, with beta PPP < beta SSS < beta UUU, while the triangle disposition is
      better than the rectangle one among the same tree species. UPPU and SPPS of mixed
      structure have the optimal effect in popular-willow-elm mixed shelterbelts.

PMID- 12216387
TI  - [Coupling relationship between plant communities' species diversity and soil
      factors in ecotone between desert and oasis in Fukang, Xinjiang].
AB  - Regression analysis was used to study the relationship between four diversity
      indices and 19 soil factors at three different soil layers in ecotone between
      desert and oasis in Fukang, Xinjiang. The results indicated that soil pH, total
      salt content, soil organic matter, Cl-, K+ + Na+, Mg2+, total nitrogen, and
      available phosphorus were correlative to species diversity significantly (P <
      0.05). The relationships between pH and diversity and between organic matter and
      diversity were best fitted in form of binomial model, and it meant that the
      highest species diversity occurred in middle of the gradient. The relationships
      between diversity and other 6 indices were in form of negative linear regression,
      showing that the contents of total salt, Cl-, K+ + Na+, Mg2+ were greater, and
      the species diversity indices were smaller. And the regression of total nitrogen
      and available phosphorus with evenness were similar to the former, that is, with
      the contents of soil total nitrogen and available phosphorus increasing, evenness
      indices decline correspondingly. The results of regression analysis between
      amount of plants and soil moisture and salt showed that plant abundance was
      influenced by soil water and salt significantly (P < 0.01).

PMID- 12216388
TI  - [Effect of elevated CO2 concentration on carbohydrate and nitrogen contents in
      seedlings foliage of three tree species in Changbai mountain].
AB  - The contents of sucrose, fructose, soluble total sugar, starch and total nitrogen
      were analyzed in seedlings of Pinus koraiensis, Pinus sylvestriformis and
      Fraxinus mandshurica grown for three growing seasons in open-top chambers in
      Changbai mountain under elevated CO2 (700, 500 mumol.mol-1) and ambient CO2 (350
      mumol.mol-1) concentrations. The results showed that in the first two growing
      seasons the treatment of 700 mumol.mol-1 CO2 accumulated the contents of starch
      in Pinus sylvestriformis and Fraxinus mandshurica seedlings, while total nitrogen
      content significantly decreased in Pinus koraiensis seedlings under 700 and 500
      mumol.mol-1 CO2. The content of starch increased and the content of total
      nitrogen decreased in Pinus koraiensis and Fraxinus mandshurica seedlings grown
      under 700, 500 mumol.mol-1 CO2 at the first two weeks in the third growing
      season. The change of starch and total nitrogen in Fraxinus mandshurica at the
      eighth week was similar to the first and second week. There was no significant
      increase or decrease of C and N content in Pinus sylvestriformis at the third
      growing season. CO2 concentration affected the forms of carbohydrate accumulation
      in foliage.

PMID- 12216389
TI  - [Effects of global warming on productivity and soil moisture in Taihang mountain:
      a transplant study].
AB  - By transferring natural vegetation with soil from high elevation to low
      elevation, a 2 degrees C warmer condition was created. In each site, 5 different
      precipitation treatments were applied to test if the temperature and
      precipitation changes under global warming will result in a lower soil moisture
      condition and, therefore, feedback negatively on vegetation productivity of the
      Taihang Mountain. Two years' field experiment suggested that, because of the low
      adaptability of Arundinelia hirta under a warmer condition, its productivity
      decreased significantly at the end of the experiment. Productivities of grass
      with better adaptability such as Themeda japonica and Artemisia sacrorum did not
      change significantly between the two sites. Tested vegetation demonstrated a
      significant increase in productivity under the higher precipitation condition by
      showing 22% increase in productivity under 20% higher precipitation treatment.
      Soil moisture condition under treatments with higher precipitation was generally
      higher than that under treatments with lower precipitation. In the warmer site,
      soil moisture became higher since the beginning of the second year.

PMID- 12216390
TI  - [Temporal and spatial change characteristics of soil elements in reclaimed slope
      forestland].
AB  - Calcium, Magnesium, Copper, Zinc, Manganese and Iron are necessary elements for
      plant growth and important indicators for soil quality evaluation. After
      forestland being reclaimed, spatial distributions of soil elements would be
      affected by plowing, erosion-deposition-transportation, and soil element
      properties. In the initial stage of forestland being reclaimed (the first and
      second year), Cu, Zn, Mn, Fe, K, Ca, and Mg in different slope locations would be
      increased. After two years, these elements would be decreased because of soil
      erosion. After six years, Cu, Fe, K, and Mg would be decreased by 1.5-4.56%. SiO2
      content on the upper slope would be increased as reclaimed year increased, but on
      the middle slope, SiO2 content would be decreased and Al element would be
      increased.

PMID- 12216391
TI  - [Soil catalase activity of main plant communities in Leymus chinensis grassland
      in northeast China].
AB  - The seasonal dynamics of soil catalase activity of three different plants
      communities in Leymus chinensis grassland in northeast China were in a parabolas
      shape. The seasonal variation of Chloris virgata community was greater than those
      of Leymus chinensis community and Puccinellia tenuiflora community, and "seed
      effect" might be the main reason. The correlation between the activity of soil
      catalase in different soil layers and environmental factors were analyzed. The
      results showed that the activity of soil catalase was decreased gradually with
      depth of soil layer. The activity of soil catalase was closely correlated with
      rainfall and air temperature, and it was affected by soil temperature, soil
      moisture, and their interactions. The correlation between the activity and
      aboveground vegetation was very significant, and the growing condition of plant
      communities could be reflected by the activity of soil catalase.

PMID- 12216392
TI  - [Geographic variation in female reproductive characteristics and egg incubation
      of Eumeces chinensis].
AB  - Geographic variation in female reproductive characteristics and egg incubation of
      Chinese skink (Eumeces chinensis) was studied by using two populations from
      eastern (Lishui, Zhejiang) and southern (Shaoguan, Guangdong) China,
      respectively. The results showed that female adults of the two populations both
      laid a single clutch per breeding season, and the clutch size, clutch mass, and
      egg mass had a positive correlation with female SVL. There was obvious geographic
      variation in head shape of females, reproductive characteristics, timing date of
      oviposition, and thermal dependence of egg incubation between two populations.
      Skinks from Shaoguan began to lay eggs in mid-May, approximately two weeks
      earlier than the timing date of skinks from Lishui. Skinks from Shaoguan produced
      more but smaller eggs. The size-specific (SVL) clutch size of skinks from
      Shaoguan outnumbered that of skinks from Lishui by 2.8 eggs. It implied there was
      a trade-off between the number and the size of offspring between populations,
      because there was no difference in size-specific clutch mass among skinks from
      both populations, and skinks within a population could produce larger clutches
      without a concomitant reduction in egg mass. Overall, compared to eggs incubated
      under 32 degrees C, eggs incubated under 24 degrees C could produce larger (SVL)
      and well-developed hatchlings with less unutilized yolks. Compared to eggs from
      Lishui incubated under the same temperature of 24 degrees C and 32 degrees C,
      eggs from Shaoguan produced hatchlings with smaller body wet mass and carcass dry
      mass. Accordingly, there was geographic variation in suitable range of incubation
      temperatures, and eggs laid by skinks from Lishui could successfully incubate in
      a wider range of temperatures.

PMID- 12216393
TI  - [Seasonal fluctuation of plant biomass in land remained bare in Hailun
      experimental station].
AB  - Analysis of the above- and under-ground biomass of the land remained bare for
      seven years and twenty years and the farmland in Hailun experimental station
      showed that total biomass increased over the bare period. There was no
      significant difference in above-ground biomass between bare lands, while the root
      biomass showed obvious difference, indicating that total biomass was differed
      mainly from root biomass between bare lands. With longer bare period, the
      ecosystem had the stronger resistance to environmental stress and the more
      stability. Meanwhile, its root biomass turnover value was small, which suggesting
      the higher ability to supply nutrient and energy stably.

PMID- 12216394
TI  - [Canopy spectral characteristics of different rice varieties].
AB  - By using spectroradiameter, canopy spectral characteristics such as reflection
      rate (alpha), absorption rate (tau), transmission rate (beta), and extinction
      coefficient(K) of different rice varieties were analyzed and compared. The
      results showed the canopy spectral characteristics were significantly different
      among different rice varieties, especially under blue radiation (400-510 nm). In
      addition, these dissimilarities were more obvious in the late stage of growth
      period.

PMID- 12216395
TI  - [Fixed ammonium content of chief paddy soil types in Hunan Province and its
      influencing factors].
AB  - By the method of Silva and Bremner, the fixed ammonium content of chief paddy
      soil types in Hunan Province and its influencing factors were studied. The
      results showed that the content of fixed ammonium in plough layer ranged from 141
      mg.kg-1 to 353 mg.kg-1, averaged 272 +/- 67 mg.kg-1, and accounted for 11.2% of
      total soil N. The content of fixed ammonium was in order of alluvial sandy soil >
      purple clayey soil > newly alluvial sandy soil > yellow clayey soil > reddish
      yellow clayey soil. There were four distribution models of fixed ammonium in the
      soil profiles: 1) fixed ammonium content increased with the increase of depth in
      the profiles; 2) fixed ammonium content decreased with the increase of depth; 3)
      there was no distinct change; and 4) abrupt increase or decrease was found in the
      profiles. The percentage of fixed ammonium to total N in soils always increased
      with the increase of depth. The fixation of NH4+ by soil was the strongest under
      30 degrees C. Long-term submergence benefited to the fixation of NH4+ in newly
      alluvial sandy soil, purple clayey soil, and alluvial sandy soil, while the
      alternation of drying and wetting contributed to the fixation of NH4+ in yellow
      clayey soil best. The content of fixed ammonium in tested soil was correlated
      with the content of clay < 0.01 mm at the significant level, and not correlated
      with the content of clay < 0.001 mm, total N, organic N, and matter.

PMID- 12216396
TI  - [Effects of ecological factors on infection process of Pyricularia grisea].
AB  - Rice blast is one of the main rice diseases. In order to discuss the occurrence
      regularity and improve the veracity of forecasting, the effects of ecological
      factors on infecting process, such as rice growth period, cultivar resistance,
      temperature, precipitation, and fertilization of nitrogen, were studied
      quantitatively. The results showed that adhering conidia on leaves, or ratio of
      infection was negatively correlative with the growth period of rice. The latent
      period of Pyricularia grisea was closely related to temperature, and within the
      range from 10 degrees C to 33 degrees C, the latent period was the shortest at 28
      degrees C. The ratio of conidia adhering on leaves was also closely related to
      precipitation, especially the intensity and duration of precipitation in the
      first 5 hours after conidia contacting leaves, and there was no obvious effect
      after 5 hours. Under certain conditions, the ratio of expansive lesions to non
      expansive lesions, the maximum area of expansive lesions, and variety resistance
      of rice were related to the rank of leaves.

PMID- 12216397
TI  - [Time-specific infection rate of Beauveria bassiana on Myzus persicae after
      topical inoculation of conidial suspension].
AB  - Conidial suspension(5 x 10(6) conidia.ml-1) of the entomopathogenic fungus,
      Beauveria bassiana BBSG8702 was used to inoculate newly emerged apterous adults
      of the green peach aphid (Myzus persicae) on detached cabbage leaves in order to
      measure time-specific infection rate of the fungal agent. The aphids of conidia
      attached were disinfected using 0.2% chlorothalonil solution at intervals of 8-56
      h after inoculation and then maintained at 10 and 20 degrees C for daily
      observation. There was a significant difference (P < 0.05) in mortality
      attributed to the fungal infection among the time intervals within 56 h at 10
      degrees C after inoculation or within 40 h at 20 degrees C. Compared with the
      control (not treated with 0.2% chlorothalonil after inoculation), time-specific
      infection rate at 10 degrees C was estimated as 22.9%, 48.8%, 64.9%, 80.4%,
      72.7%, and 98.3% within 8 h, 16 h, 24 h, 32 h, 40 h, and 56 h after inoculation,
      respectively. The same estimates at 20 degrees C were 31.6%, 48.8%, 58.6%, 86.9%,
      97.2%, and 98.7%, respectively. The results indicate that the first 24 h after
      inoculation was crucial to the infection of B. bassiana to M. persicae. Effective
      infection with the first 24 h accumulated to 59-65% at 10-20 degrees C.

PMID- 12216398
TI  - [Structure and function of township agroecosystems and their correlation in
      northern plain areas of Zhejiang Province].
AB  - The structure and functions of 15 township agroecosystems in northern plain areas
      of Zhejiang Province were investigated and studied. Both cluster analysis and
      correlation analysis were used to study the correlation between the holistic
      structure and function of the agroecosystems. The results showed that cluster
      analysis could reveal the correlation between the holistic structure and function
      of the agroecosystems, which was conducive for mastering the direction of
      holistic structural adjustment. Correlation analysis could identify the extent
      and direction of correlation between specific structural and functional
      indicators, which could serve as the basis for specific structural adjustment for
      optimization of functions.

PMID- 12216399
TI  - [Influence of environmental factors on the decomposition of organic carbon in
      agricultural soils].
AB  - To quantitatively investigate the effects of environmental factors on organic
      carbon decomposition, CO2-C was measured from the incubation of wheat and rice
      straw as well as their roots mixed with a paddy soil over a 90-day period.
      Results showed that decomposition of the straw carbon was faster than that of the
      roots. Amount of CO2-C released from the organic matter decomposition was
      quantitatively related to its properties of C/N ratio. Increase of temperature
      within a lower temperature range enhanced greatly the decomposition while such an
      enhancement weakened within a higher temperature range. Under the moist
      condition, the temperature coefficient of organic carbon decomposition declined
      exponentially with the incubation time. The temperature coefficient did not
      significantly decrease with the time for the submerged condition after one-week
      incubation. The effect of water status showed that the decomposition at the water
      contents of 300 g.kg-1 and 500 g.kg-1 was faster than that under the treatments
      of 200 g.kg-1 and the submerged. Within the first month period of incubation,
      carbon amount released from the incubation of wheat straw was negatively related
      to the clay fraction of the soils.

PMID- 12216400
TI  - [Design and purification performance of vertical flow constructed wetland].
AB  - The technical design of small-scale plots (SSPs) of constructed wetland (CW) was
      described along with details of some associated wastewater purification effects
      in winter. Plots were comprised of two chambers. One chamber induced downward
      flow, while the other created upward-flow. During Oct. 1997-Jan. 1998, the
      average plot removal rates for CODCr, BOD5 and total suspended solids were 53.6%,
      78.7% and 80.2%, respectively. Reductions of bacteria, total coliforms (TC),
      fecal coliforms (FC) and algae were 99.4%, 85.9%, 89.7% and 97.7%, respectively.
      The mean removal rates of Kjeldahl nitrogen (KN), ammonium (NH4(+)-N) and total
      phosphorus (TP) were 39.2%, 16.5% and 25.8%. The treatment effects were not
      significantly different from each other. Concentrations of nitrate (NO3(-)-N) in
      effluents were higher than those of the influent, and nitrate concentrations in
      the effluents of plant-systems were higher than those of the control. This
      indicated that presence of macrophytes enhanced nitrification in the CW. The
      downward followed by upward flow CW performed better in removing contaminants and
      microorganisms from polluted surface water. It is an improved technology to
      purify water quality and rehabilitation of aquatic ecosystems.

PMID- 12216401
TI  - [Effects of constructed wetlands on treating with nitrogen and phosphorus in
      wastewater from hoggery].
AB  - Using plant species Vetiveria zizanioides (VCWS) and Cyperus alternifolius (CCWS)
      respectively, two constructed wetlands (CWS) with size of 1.0 m x 0.5 m x 0.8 m
      were established. The purifying function and its change pattern among different
      seasons, influent concentration and hydraulic retention time (HRT) of CWS on
      nitrogen and phosphorus in wastewater from a hoggery was studied throughout four
      seasons in the year. The results showed that the effects of HRT and wastewater
      concentration on the removal rate of NH3-N and S-PO4(3-) were obvious in both
      VCWS and CCWS. High removal rates of NH3-N and S-PO4(3-) were obtained in CCWS
      and VCWS in spring. Significant removal of TN in wastewater existed in CCWS and
      VCWS in autumn, while significant removal of TP in wastewater existed only in
      VCWS. The removal of TP or S-PO4(3-) against the HRT in CWS followed exponential
      function. The rates of P removal in winter and summer changed with the influent
      concentrations. Under the same HRT, the change of S-PO4(3-) concentrations in
      outflow against the influent concentration followed a linear relationship.

PMID- 12216402
TI  - [Allelopathic effect of root exudates on pathogenic fungi of root rot in
      continuous cropping soybean].
AB  - Allelopathic effect of root exudates on pathogenic fungi of root rot in
      continuous cropping soybean was studied by sand culture, water culture, and
      indoor culture experiments. The results showed that allelopathic promotion of
      root exudates on the growth of Fusarium semitectum, Gliocladium roseum and
      Fusarium oxysporum, especially Fusarium semitectum reached significant level or
      especially significant level in continuous cropping soybean compared with the
      control. Allelopathic promotion of root exudates on the growth of Fusarium
      semitectum and Gliocladium roseum in continuous cropping soybean was distinctly
      larger than that in rotation soybean, and the difference reached significant
      level under their low concentration. Allelopathic promotion of high concentration
      of root exudates on the growth of Fusarium semitectum was smaller than that of
      low concentration of root exudates, and the difference reached significant level
      in continuous cropping soybean. Allelopathic inhibition of high concentration of
      phthalic acid and propanedioic acid (L5 and B5) on the growth of Fusarium
      semitectum. Gliocladium roseum and Fusarium oxysporum, especially Fusarium
      semitectum reached significant level or especially significant level compared
      with the control. However, allelopathic promotion of low concentration of
      phthalic acid and propanedioic acid on the growth of Fusarium semitectum,
      Gliocladium roseum and Fusarium oxysporum partly reached significant level.

PMID- 12216403
TI  - [Preliminary study on anti-baculovirus mechanism of feeding housefly larvae
      (Musca domestia) and population infection model of outbreaking epidemic disease
      of shrimp (Panaeus chinensis)].
AB  - Based on indoors individual infection and outdoor population infection of shrimp,
      population infection model was established and anti-baculovirus mechanism of
      housefly larvae was analyzed. The results showed that 50% death time of the
      shrimps feeding with housefly larval reasonably was prolonged 3-5 times compared
      with the control group. Prophenoloxidase system of prawns was activated while
      feeding shrimps with housefly larval 7-10 days before infection by baculovirus,
      and prophenoloxidase activity was 3 times higher than the control group. The
      establishment of population infection model illustrated clearly important role of
      housefly larvae in improving the immunity of shrimps from baculovirus.

PMID- 12216404
TI  - [Variation of bacteria numbers in fish-shrimp mix-culturing ecosystem].
AB  - The study on variation of bacteria numbers in Penaeus chinensis-fish mix
      culturing ecosystem in 1997. Indicated that at the beginning of culturing season,
      total number of heterotrophic bacteria and that of nitrate-reducing bacteria in
      mix-culturing ponds was low, but it was higher than that in mono-culturing shrimp
      pond. With time going on, the number of bacteria in mono-culturing pond increased
      rapidly and remained at a high level in August and September, an that in mix
      culturing ponds also increased. But the latter increased slowly, and it was never
      over 10(4) cells.ml-1 and dropped in September. Number of bacteria in bottom of
      the ponds varied with the similar regulation, but the numbers was 10-100 times
      higher. The numbers of vibrio in mix-culturing ponds was always lower than that
      in contrastive pond at the same time. So, in fish-shrimp mix-culturing ponds, the
      contents of organic matter were lower and the total amount and variability of
      phytoplankton were higher than corresponding items in mono-culturing pond. It was
      concluded that mix-culture could stimulate and control the growth of
      heterotrophic bacteria, accelerate the degradation of organic pollutants,
      consequently fasten and stabilize the circulation of mater in ecosystem of ponds
      in culturing season.

PMID- 12216405
TI  - [Effect of stocking density on growth of juvenile Acipenser schrenckii].
AB  - The effect of stocking density on growth of juveniles Acipenser schrenckii was
      studied, and the results showed that juveniles Acipenser schrenckii reared for 28
      days in a flowing water system under different stocking densities of 0.232,
      0.665, 1.347, and 2.469 kg.m-2 grew in allometry. There were no significant
      differences between the final and initial SV under the four treatments. The
      growth efficiency, DWG, NY, and SGR of juveniles were decreased with the increase
      of stocking densities. However, the FCR and NY were increased with the increase
      of stocking densities. There were significant differences between these
      parameters under the low and high densities treatment after 28 days. Moreover,
      there was a significant negative linear correlation between stocking density (D)
      and special growth rate (SGR).

PMID- 12216406
TI  - [Effect of salinity and body weight on the oxygen consumption of Oreochromis
      niloticus x O. mossambicus].
AB  - The effects of salinity and body weight on oxygen consumption of Taiwan red
      tilapia (Oreochromis niloticus x O. mossambicus) were studied. The fish was
      divided into three groups by their body weight: 1.57-4.87 g (G1), 7.07-18.23 g
      (G2) and 31.50-52.41 g (G3). The results showed that oxygen consumption at
      different salinities was significantly different (P < 0.01). The rates of oxygen
      consumption in G1 and G2 were highest, with 0.41 mg O2.g-1.h-1 for G1, and 0.34
      mg O2.g-1.h-1 for G2 respectively at salinity 7@1000; while G3 had highest level
      with 0.30 mg O2.g-1.h-1 at 35@1000. The lowest oxygen consumption level appeared
      at different salinities with the different body weight. The lowest level in G1,
      0.27 mg O2.g-1.h-1, appeared at salinity 14@1000. G2 and G3 had lowest oxygen
      consumption level at 21@1000, with 0.22 mg O2.g-1.h-1 and 0.13 mg O2.g-1.h-1
      respectively. ANOV showed that oxygen consumption was significantly affected by
      the interaction of salinity and body weight.

PMID- 12216407
TI  - [Perspectives in researches on grassland ecology for the early 21st century in
      China].
AB  - Grassland degeneration is a prominent problem in China. More in-depth studies
      should be carried out on the key problem--grassland degeneration for Chinese
      grassland ecologists in the early 21st century. Some hot research fields were
      restoration ecology, interface ecology, grazing ecology, health diagnoses and
      evaluation for grasslands. Among them, restoration ecology was the foundation for
      restoring degenerative grasslands; interface ecology involved with the point of
      contact for analyzing degenerative grasslands; grazing ecology was the effective
      way to control degenerative grasslands; diagnoses of grassland health benefited
      accurately appraising degenerative levels of grasslands; and evaluation for
      grassland was also considered as an estimation on services and benefits of
      grassland ecosystems.

PMID- 12216408
TI  - [Sustainable management for farmland shelterbelts].
AB  - The spatio-temporal pattern of shelterbelt regeneration is an important issue
      which determintes whether shelterbelt network produces protective effects
      sustainably. This article developed a new method of imitating "normal forest" to
      manage shelterbelts. Based on an administrative village as an organized
      management unit, each shelterbelt in the organized management unit will be
      individually regenerated and regulated, until the number of the shelterbelts in
      each age-class from young to mature ones will be equal, and the shelterbelts in
      each age-class will be spatially distributed uniformly in the shelterbelt network
      of an organized management unit. Consequently, this method might temporally
      ensure sustainable and stable ecological services which are provided by the
      shelterbelts in an organized management unit.

PMID- 12216409
TI  - [Interaction between rare earths and nitrogen and phosphorus in soil-plant
      system].
AB  - Interaction between rare earths (REs) and nitrogen and phosphorus in soil-plant
      system is a hot spot in the research field of safety assessment for agricultural
      utilized rare earths. This interaction directly affects the productivity of
      arable soil, and is beneficial to assessing the response of rare earths to crop
      production and the eco-environmental safety. The interaction between rare earths
      and nitrogen and phosphorus in soil-plant system is briefly summarized, and it's
      put forward that the interaction between rare earths and nitrogen and phosphorus
      in the rhizophere of crop, surface layer of arable soil, and plant should be
      further investigated.

PMID- 12216410
TI  - [Complexity of land ecosystem].
AB  - In recent years, complexity studies has become a new research region and been
      widely applied in engineering, biology, economy, management, military, police and
      sociology. In this paper, from the view of complex science, the main complexity
      characteristics of land ecosystem were described, furthermore, the application of
      fractal, chaos, and artificial neural network on the complexity of land ecosystem
      were also discussed.

PMID- 12216411
TI  - [Current situation and prospect on the remediation of soils contaminated by heavy
      metals].
AB  - Physio-chemical techniques and phytoremediation are the important methods for
      solving heavy metal pollution of environment. According to the processes and
      mechanisms of reactions, physio-chemical techniques can be divided into chemical
      immobilization, soil washing and electrokinetic remediation, while
      phytoremediation includes phytostabilization, phyto-volatilization and phyto
      extraction. The principles, advantages, disadvantages, feasibility and future
      research trends of the techniques were reviewed.

PMID- 12216412
TI  - [Assessing indices of container seedling quality].
AB  - In this paper, the assessing indices of container seedlings quality were
      synthesized in accordance with growth and physiological factors. The results
      showed that the seedling quality might be determined by the dormancy state of
      terminal bud, nutrient condition of plant, and the state of root system. The
      critical quality indices should include stem diameter at soil surface, dry weight
      of terminal bud, and soluble sugar content. Moreover, some indices such as root
      system vitality and dry weight of plant were also important.

PMID- 12216413
TI  - [Correlations of shoot and root growth and its role in screening for aluminum
      tolerance in wheat].
AB  - A large-volume solution culture and a small-pot soil test were adopted to screen
      for aluminum tolerance in wheat. Significant correlations were observed between
      root and shoot tolerance indices in wheat genotypes by using the same or
      different screening method. It was also shown that root tolerance parameters such
      as relative root length (RRL) and relative root dry weight (RRW) had more
      sensitive for differentiating aluminum tolerance in wheat genotypes indicated by
      higher standard deviation (SD), coefficient of variation (CV), and distribution
      of data. Although shoot tolerance parameters, such as relative shoot length (RSL)
      and relative shoot dry weight (RSW) had less sensitive for differentiating
      aluminum tolerance within wheat genotypes indicated by lower SD, CV, and
      distribution of data, shoot growth parameters were reliable indicators of Al
      tolerance because they were sufficient to discriminate Al-tolerant and Al
      sensitive genotypes in wheat. Shoot growth especially shoot length could be
      easily, rapidly, and non-destructively determined, and used effectively to screen
      for aluminum tolerance in a large-scale screening or breeding program.

PMID- 12216414
TI  - Assessment of incidence of neonatal tetanus in selected districts of the Lao
      People's Democratic Republic.

PMID- 12216415
TI  - Modelling blood flow regulation by nitric oxide in psoriatic plaques.
AB  - Psoriasis is a common skin disease, with a clinical appearance of red, scaly
      lesions, known as plaques. Recent experimental research has shown that the
      ubiquitous cell-signalling molecule nitric oxide (NO) is actively synthesized
      within these plaques by the iNOS enzyme. In contrast, NO production from normal,
      healthy skin is a byproduct of the reduction of nitrite in sweat. Measurement of
      NO release rates at the skin surface are 100 times greater from psoriatic lesions
      than normal skin. We propose a mathematical model for the dynamics of NO within
      psoriatic plaques, that incorporates diffusion, production in the basal
      epidermis, decay within the plaque, and active scavenging by red blood cell
      haemoglobin; this last effect introduces a key nonlinearity into the model. We
      present numerical simulations of the model in two space dimensions, and then
      describe an approximation that reduces the model to two coupled ordinary
      differential equations. This reduced system can be solved exactly, giving an
      approximation for the NO release rate as an explicit function of model
      parameters. We use this approximation to explain some recent, surprising
      experimental results.

PMID- 12216416
TI  - The cleavage plane will bend when one aster of the mitotic apparatus stops
      growing in compressed sea urchin eggs.
AB  - Astral microtubules are elongated greatly during anaphase and telophase in sea
      urchin eggs. The surface density of microtubules reaching the cell surface can be
      defined at each surface point. Gradients of the surface-density function were
      assumed to drive membrane proteins whose accumulation causes the formation of
      contractile-ring microfilaments. An equation was constructed to calculate the
      movements of the membrane proteins on a curved surface. The equation was applied
      to eggs compressed between a coverslip and a glass slide by regarding the egg
      shape as an oblate spheroid. The simulations explained the observations that
      contractile-ring microfilaments locally appeared and then developed into a
      complete ring in compressed eggs. When one aster in the mitotic apparatus stopped
      growing during anaphase, the equation predicted that the zone of contractile-ring
      microfilaments is displaced toward the inactivated aster, curves in the view from
      above and tapers off toward the cell edge. The curve gets sharper as eggs are
      compressed more greatly and as microtubules from the growing aster penetrate more
      deeply into the opposite hemisphere. The predictions were compared with the
      observations by Ishii and Shimizu in 1995 and by Hamaguchi in 1998 regarding the
      furrow formation by the asymmetric mitotic apparatus.

PMID- 12216417
TI  - Mathematical modelling of flow through vascular networks: implications for tumour
      induced angiogenesis and chemotherapy strategies.
AB  - Angiogenesis, the formation of blood vessels from a pre-existing vasculature, is
      a process whereby capillary sprouts are formed in response to externally supplied
      chemical stimuli. The sprouts then grow and develop, driven initially by
      endothelial cell migration, and organize themselves into a branched, connected
      network structure. Subsequent cell proliferation near the sprout-tip permits
      further extension of the capillary and ultimately completes the process.
      Angiogenesis occurs during embryogenesis, wound healing, arthritis and during the
      growth of solid tumours. In this paper we initially generate theoretical
      capillary networks (which are morphologically similar to those networks observed
      in vivo) using the discrete mathematical model of Anderson and Chaplain. This
      discrete model describes the formation of a capillary sprout network via
      endothelial cell migratory and proliferative responses to external chemical
      stimuli (tumour angiogenic factors, TAF) supplied by a nearby solid tumour, and
      also the endothelial cell interactions with the extracellular matrix. The main
      aim of this paper is to extend this work to examine fluid flow through these
      theoretical network structures. In order to achieve this we make use of flow
      modelling tools and techniques (specifically, flow through interconnected
      networks) from the field of petroleum engineering. Having modelled the flow of a
      basic fluid through our network, we then examine the effects of fluid viscosity,
      blood vessel size (i.e., diameter of the capillaries), and network
      structure/geometry, upon: (i) the rate of flow through the network; (ii) the
      amount of fluid present in the complete network at any one time; and (iii) the
      amount of fluid reaching the tumour. The incorporation of fluid flow through the
      generated vascular networks has highlighted issues that may have major
      implications for the study of nutrient supply to the tumour (blood/oxygen supply)
      and, more importantly, for the delivery of chemotherapeutic drugs to the tumour.
      Indeed, there are also implications for the delivery of anti-angiogenesis drugs
      to the network itself. Results clearly highlight the important roles played by
      the structure and morphology of the network, which is, in turn, linked to the
      size and geometry of the nearby tumour. The connectedness of the network, as
      measured by the number of loops formed in the network (the anastomosis density),
      is also found to be of primary significance. Moreover, under certain conditions,
      the results of our flow simulations show that an injected chemotherapy drug may
      bypass the tumour altogether.

PMID- 12216418
TI  - A survey of unequal crossover systems and their mathematical properties.
AB  - We present a model of gene duplication by means of unequal crossover (UCO) where
      the probability of any given pairing between homologous sequences scales as a
      penalty factor pz < or = 1, with z the number of mismatches due to asymmetric
      sequence alignment. From this general representation, we derive several limiting
      case models of UCO, some of which have been treated elsewhere in the literature.
      One limiting case is random unequal crossover (RUCO), obtained by setting p = 1
      (corresponding to equiprobable pairings at each site). Another limiting case
      scenario (the 'Krueger-Vogel' model) proposes an optimal 'endpoint' alignment
      which strongly penalizes both overhang and deviations from endpoint matching
      positions. For both of these scenarios, we make use of the symmetry properties of
      the transition operator (together with the more general UCO properties of copy
      number conservation and equal parent-offspring mean copy number) to derive the
      stationary distribution of gene copy number generated by UCO. For RUCO, the
      stationary distribution of genotypes is shown to be a negative binomial, or
      alternatively, a convolution of geometric distributions on 'haplotype'
      frequencies. A different type of model derived from the general representation
      only allows recombination without overhang (internal UCO or IntUCO). This process
      has the special property of converging to a single copy length or a distribution
      on a pair of copy lengths in the absence of any other evolutionary forces. For
      UCO systems in general, we also show that selection can readily act on gene copy
      number in all of the UCO systems we investigate due to the perfect heritability
      (h 2 = 1) imposed by conservation of copy number. Finally, some preliminary work
      is presented which suggests that the more general models based on misalignment
      probabilities seem to also converge to stationary distributions, which are most
      likely functions of parameter value p.

PMID- 12216419
TI  - Pattern formation in reaction-diffusion models with nonuniform domain growth.
AB  - Recent examples of biological pattern formation where a pattern changes
      qualitatively as the underlying domain grows have given rise to renewed interest
      in the reaction-diffusion (Turing) model for pattern formation. Several authors
      have now reported studies showing that with the addition of domain growth the
      Turing model can generate sequences of patterns consistent with experimental
      observations. These studies demonstrate the tendency for the symmetrical
      splitting or insertion of concentration peaks in response to domain growth. This
      process has also been suggested as a mechanism for reliable pattern selection.
      However, thus far authors have only considered the restricted case where growth
      is uniform throughout the domain. In this paper we generalize our recent results
      for reaction-diffusion pattern formation on growing domains to consider the
      effects of spatially nonuniform growth. The purpose is twofold: firstly to
      demonstrate that the addition of weak spatial heterogeneity does not
      significantly alter pattern selection from the uniform case, but secondly that
      sufficiently strong nonuniformity, for example where only a restricted part of
      the domain is growing, can give rise to sequences of patterns not seen for the
      uniform case, giving a further mechanism for controlling pattern selection. A
      framework for modelling is presented in which domain expansion and boundary
      (apical) growth are unified in a consistent manner. The results have implications
      for all reaction-diffusion type models subject to underlying domain growth.

PMID- 12216420
TI  - An improved algorithm for statistical alignment of sequences related by a star
      tree.
AB  - The insertion-deletion model developed by Thorne, Kishino and Felsenstein (1991,
      J. Mol. Evol., 33, 114-124; the TKF91 model) provides a statistical framework of
      two sequences. The statistical alignment of a set of sequences related by a star
      tree is a generalization of this model. The known algorithm computes the
      probability of a set of such sequences in O(l2k) time, where l is the geometric
      mean of the sequence lengths and k is the number of sequences. An improved
      algorithm is presented whose running time is only O(2(2k)lk).

PMID- 12216421
TI  - Quantifying the strength of ligand antagonism in TCR triggering.
AB  - Triggering of the T cell receptor (TCR) may be antagonized by ligands that are
      slight variants of the immunogenic peptide. This paper proposes a mathematical
      model to quantify the strength of the antagonistic effect. The model is based on
      the kinetics of association and dissociation of TCR and peptide/major
      histocompatibility (pMHC) molecules, and incorporates TCR triggering according to
      a kinetic proofreading mechanism. Model analysis indicates that while the average
      lifetime of the TCR/pMHC complex is the basic determinant of the contribution to
      TCR triggering made by the ligand, the affinity of the ligand and its MHC
      presentation level are also important. However, these contributions depend on the
      kinetic limitation regime. There is a continuum of limitation regimes, at the
      extremes of which are found TCR limitation and MHC limitation. Both ligand
      affinity and TCR and pMHC densities determine whether TCR triggering is TCR
      limited or MHC limited. The changing importance of affinity and antigen
      presentation level under various kinetic limitation regimes may explain the
      respective roles of antagonistic and agonistic self peptides in thymic selection.
      Moreover, TCR down-regulation under TCR-limited conditions may allow the T cell
      to differentiate between the average lifetime of the TCR/pMHC complex and the
      presentation level of the ligand. A method for experimental differentiation
      between passive and active antagonistic effects is proposed which exploits the
      differences between TCR and MHC limitation.

PMID- 12216422
TI  - Fertility assurance through extrapair fertilization, and male parental effort.
AB  - Extrapair paternity (EPP) has been observed in many formally monogamous species.
      Male pursuit of extrapair fertilizations (EPF) is explained by the advantages of
      having offspring that receive essential paternal care from other males. Because
      females are capable of exercising a degree of control over the post-copulatory
      sperm competition, EPP's persistence indicates that females benefit from EPF.
      Thus, EPP involves cooperation between mated females and extrapair males. On the
      other hand, mated males exhibit a spectrum of anti-cuckolding strategies. Hence,
      extrapair attributes of diverse species and populations reported in the
      literature are particular solutions of evolutionary games involving gender
      specific cuckolding/anti-cuckolding strategies. Here we use game theoretical
      methods to study the effect of male paternal effort conserving strategies in
      situations where females seek EPF for reasons of genetic compatibility and/or in
      pursuit of genetic diversity for their offspring. Our results indicate that in
      these circumstances pursuit of EPF is the only evolutionary stable female
      strategy. Males, on the other hand, have two, mutually exclusive, evolutionary
      stable strategies: males that restrict parental care regardless of their mate's
      fidelity, and males that never restrict parental care. That is, when females seek
      EPF for reasons of fertility assurance and/or genetic diversity, the conditional
      male strategy--therein the male's parental efforts are based on his certainty of
      paternity--loses in competition with the unconditional strategies.

PMID- 12216423
TI  - Adolescent sexuality, cultural sensitivity and the teachings of the Catholic
      Church.
AB  - In recent years it has been increasingly recognized that physicians must be
      sensitive to the cultural beliefs of their patients. This is especially important
      for physicians who deal with sexuality, especially when dealing with adolescents.
      Despite this, many mainstream text-books and journal articles ignore the
      teachings of the largest single religious denomination in the United States, the
      Roman Catholic Church. The Church has clear teachings regarding sex education,
      masturbation, contraception and abortion. Physicians should be aware of these
      teachings and be sensitive to the needs of Catholic adolescents when dealing with
      these issues.

PMID- 12216424
TI  - Selective transarterial embolization and hysteroscopic removal of a placental
      polyp with preservation of reproductive capacity.
AB  - OBJECTIVE: To evaluate the role of transarterial embolization followed by
      hysteroscopic removal of a placental polyp with preservation of reproductive
      capacity. STUDY DESIGN: Three patients with placental polyps with abundant blood
      flow, suspected on ultrasonography with color Doppler imaging and on magnetic
      resonance imaging, were studied. They underwent transarterial embolization
      followed by hysteroscopic removal of the polyp. Transarterial embolization of the
      bilateral uterine arteries was carried out using an absorbable gelatin sponge.
      Selective removal via hysteroscopy was performed on the following day using a
      cutting loop without electrical stimulation. The polyp was gradually resected to
      the level of the surrounding endometrium. RESULTS: Complete removal of the
      placental polyp was achieved in all patients. The presence of a placental polyp
      was confirmed by pathologic examination. The operative time was ranged from 26 to
      53 minutes. In all cases, no complications were noted, and bleeding was minimal
      during and immediately after the procedure. Postoperative ultrasonography
      demonstrated a uterine cavity free of residual mass in each case. CONCLUSION:
      Transarterial embolization of the uterine arteries followed by selective
      hysteroscopic removal is a safe and effective method of minimizing bleeding and
      preserves fertility in the treatment of placental polyps with an abundant blood
      flow.

PMID- 12216425
TI  - Localization of the Fas-Fas ligand system in human fetal membranes.
AB  - OBJECTIVE: To determine if fetal membranes might be one of the sources of Fas and
      Fas ligand in amniotic fluid. STUDY DESIGN: Human fetal membranes from elective
      cesarean section (n = 6) were fixed in paraformaldehyde. Rolls of
      paraffinembedded fetal membranes were cut into 5-micron sections. After blocking
      with horse and goat sera, sections were incubated overnight with primary
      antibodies followed by the appropriate secondary antibodies. Avidin-biotin
      complex and diaminobenzidine were used for immunoperoxidase localization.
      Expression of Fas and Fas ligand was read by light microscopy. RESULTS: Both Fas
      and Fas ligand were localized in amnion, chorion and decidual layers. In amnion,
      Fas and Fas ligand were expressed predominantly in epithelial cells and
      fibroblasts, while there was no immunostaining in the subepithelial compact
      connective tissue. In the chorion, the expression was mainly in the chorionic
      trophoblast, with inconsistent expression in the reticular layer. In the decidua,
      the expression of Fas and Fas ligand was less prominent than in amnion and
      chorion. CONCLUSION: Localization of Fas and Fas ligand in human fetal membranes
      suggests that fetal membranes could be one of the sources of soluble Fas and Fas
      ligand in amniotic fluid.

PMID- 12216426
TI  - Transvaginal hydrolaparoscopy vs. conventional laparoscopy for evaluating
      unexplained primary infertility in women.
AB  - OBJECTIVE: To verify the usefulness and reliability of transvaginal
      hydrolaparoscopy (THL) as a screening tool for evaluating infertility in women in
      comparison with conventional diagnostic laparoscopy. STUDY DESIGN: Sixty
      consecutive women with unexplained primary infertility were prospectively
      enrolled into the study. After examination of the whole pelvic cavity, tubal
      patency was evaluated and the uterine cavity studied by hysteroscopy. Immediately
      after THL, conventional laparoscopy was performed. Main outcome measures were the
      success rate of accessing the pouch of Douglas, rate of complete examinations,
      rate of complications and accuracy of THL in comparison with laparoscopy.
      RESULTS: Success rate of accessing the pouch of Douglas and performing THL was
      93.3%. The rate of complete evaluation of all the pelvic structures was 76.8%. In
      studying tubal pathology, 77.8% agreement was found between the two techniques.
      Diagnosis of endometriosis was correct in 55.5% of patients. Overall, THL results
      correlated closely with conventional laparoscopic results in 92.86%, but the
      diagnostic accuracy of THL was 100% in cases of complete pelvic evaluation.
      CONCLUSION: THL is a feasible, reliable and safe procedure and can be considered
      an alternative procedure for evaluating infertility in women. In cases of
      incomplete pelvic evaluation or abnormal findings, conventional laparoscopy is
      indicated as the second step in the evaluation.

PMID- 12216427
TI  - Normal ultrasonic evaluation of amniotic fluid in low-risk patients at term.
AB  - OBJECTIVE: To study women at the time of admission to the labor and delivery unit
      to determine which type of ultrasonographic assessment of the amniotic fluid-
      amniotic fluid index (AFI), single deepest vertical pocket (DVP) or amniotic
      fluid distribution (AFD)--had the greatest clinical utility in predicting labor
      complications. STUDY DESIGN: Patients not at term, with a nonvertex presentation,
      or with ruptured membranes, polyhydramnios, or known maternal or congenital
      abnormalities were excluded. We included 266 low-risk pregnant women admitted for
      labor. Medical charts were reviewed for documentation of meconium-stained
      amniotic fluid (Mec), cesarean section (C/S) for fetal indications and admissions
      to the neonatal intensive care unit (NICU). Sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) for AFI, DVP and AFD
      were calculated in relation to the three outcome variables. Positive findings
      were defined as: AFI < 5.0, DVP < 2.5 cm and AFD, sum of the two lower quadrants
      of the AFI with a lower value than the sum of the two upper quadrants. RESULTS:
      Mec was documented in 56 patients (21%), 13 patients (4.8%) had a C/S for fetal
      indications, and 4 infants (1.5%) were admitted to the NICU. Abnormal AFI was
      detected in 35 patients (13%), abnormal DVP in 38 patients (14%) and abnormal AFD
      in 117 patients (44%). PPV and NPV for prediction of Mec, C/S and NICU were: Mec
      31% and 80% for AFI, 26% and 80% for DVP; 31% and 91% for AFD; C/S 8.6% and 95%
      for AFI, 5% and 95% for DVP; 8.6% and 100% for AFD and NICU, 0% and 98% for AFI,
      0% and 95% for DVP, and 2.7% and 99% for AFD. CONCLUSION: Normal ultrasonographic
      values for AFI and AFD are associated with a very low risk of labor
      complications.

PMID- 12216428
TI  - Accidental out-of-hospital delivery as an independent risk factor for perinatal
      mortality.
AB  - OBJECTIVE: To determine maternal characteristics and perinatal outcomes of
      unattended out-of-hospital deliveries. STUDY DESIGN: A population-based study
      including all singleton deliveries between 1988 and 1999. Maternal
      characteristics and pregnancy outcomes of accidental out-of-hospital births were
      compared with those of women who delivered in the hospital. Multiple logistic
      regression analysis was performed to investigate independent risk factors for out
      of-hospital deliveries. Another model was constructed to assess the independent
      risk of out-of-hospital delivery for perinatal mortality. RESULTS: The incidence
      of unattended, out-of-hospital deliveries was 2% (2,328/114,938). Multiparity,
      Bedouin ethnicity and lack of prenatal care were independently associated with
      out-of-hospital deliveries. Parturients who delivered out of hospital had a
      significantly lower rate of previous cesarean deliveries. Perinatal mortality was
      significantly higher among out-of-hospital deliveries, and those newborns were
      significantly more likely to be small for gestational age as compared to newborns
      with in-hospital births. In a multivariable model investigating risk factors for
      perinatal mortality, out-of-hospital delivery was an independent risk factor for
      perinatal mortality. Other significant risk factors were Bedouin ethnicity and
      lack of prenatal care. CONCLUSION: Accidental out-of-hospital birth, associated
      with multiparity, Bedouin ethnicity and lack of prenatal care, is an independent
      risk factor for perinatal mortality.

PMID- 12216429
TI  - Cost-effectiveness analyses in obstetrics & gynecology. Evaluation of
      methodologic quality and trends.
AB  - OBJECTIVE: To evaluate methodologic quality and trends of cost-effectiveness
      analyses (CEAs) published in Obstetrics & Gynecology. STUDY DESIGN: Ten
      methodologic principles that should be incorporated in CEAs are used to evaluate
      CEAs published in Obstetrics & Gynecology from 1966 through 1999. We included
      articles that were cost-effectiveness or cost-benefit analyses or performed such
      analyses as part of their studies. RESULTS: Thirty-four CEAs met our inclusion
      criteria. Seven (20%) analyses adhered to 10, five (15%) to 9, and two (6%) to 8
      of the 10 methodologic principles. The mean (+/- SD, median) number of principles
      to which studies adhered was 5.7 (+/- 3.3, 4). Studies had high compliance (> or
      = 85%) with principles of research questions, probabilities and effectiveness
      measures. Studies significantly improved over time in adherence to principles of
      time frame, perspective, costs, incremental analysis, sensitivity analysis,
      discounting and total score (all P < .05). CONCLUSION: The CEAs evaluated adhered
      to approximately half the methodologic principles for performing CEAs but showed
      significant improvements in quality over time. Understanding the methodology of
      CEAs is critical for researchers, editors and readers to accurately interpret the
      results of the growing body of CEA studies.

PMID- 12216430
TI  - Cervical fluid oncofetal fibronectin as a predictor of early ectopic pregnancy.
      Is it affected by blood contamination?
AB  - OBJECTIVE: To evaluate (1) the diagnostic usefulness of oncofetal fibronectin
      (fFN) in the cervical fluid in unruptured ectopic pregnancy, and (2) the
      contribution of maternal blood contamination of the specimen to the test results.
      STUDY DESIGN: A total of 111 cases in the first trimester of pregnancy, including
      12 cases of ectopic pregnancy, 26 of spontaneous abortion and 73 of viable
      intrauterine pregnancy, were studied. fFN was determined with a commercial enzyme
      linked immunosorbent assay kit with a threshold of 50 ng/mL in cervical fluid. To
      determine the effect of blood contamination on the fFN assay, the positive rate
      of the fFN test was examined when maternal blood in the first trimester was mixed
      with the dilution buffer. RESULTS: Eighty-three percent (10/12), 38% (10/26) and
      12% (9/73) of cases with ectopic pregnancy, miscarriage and normal pregnancy,
      respectively, were positive for fFN. The positive rate in ectopic pregnancy was
      significantly higher than in normal pregnancy and spontaneous abortion. The test
      was positive for fFN in 8% with 0.5% of blood contamination, 67% with 1%
      contamination and 100% with 10% contamination.

PMID- 12216431
TI  - Leptin concentrations in the umbilical vein and artery. Relationship to maternal
      and neonatal anthropometry.
AB  - OBJECTIVE: To determine the relationships between serum leptin levels in the
      umbilical vein (UV) and artery (UA) and the anthropometry of mothers and
      neonates. STUDY DESIGN: Blood was taken from 61 pregnant women who were admitted
      for delivery and from the umbilical vein and artery just before delivery of the
      placenta. Leptin level was measured by immunoradiometric assay. Comparisons
      between serum leptin concentrations in UVs and both maternal and neonatal
      anthropometry were made according to neonatal sex. RESULTS: Mean leptin UA and UV
      concentrations in female infants were significantly higher than those in male
      infants (both, P = .002). Leptin concentrations in UVs of the total infants were
      related to maternal body weight and body mass index preconceptionally as well as
      at birth, to neonatal birth weight, to gestational age, to Kaup index and to body
      fat content of the infants. CONCLUSION: A sex difference was observed not only in
      serum leptin concentrations UA and UV but also in the degree of significance
      between the relationship of cord leptin and both maternal and neonatal
      anthropometry. Also, the UA leptin level had a closer relationship to neonatal
      anthropometry, but the UV leptin level was more closely related to maternal
      anthropometry.

PMID- 12216433
TI  - Early-pregnancy glucose screening for gestational diabetes mellitus.
AB  - OBJECTIVE: To determine the accuracy of the 50-g, one-hour glucose screening test
      administered at 16 weeks of pregnancy for identifying women with gestational
      diabetes mellitus. STUDY DESIGN: Two hundred fifty-five women underwent 50-g, one
      hour glucose screening tests at 16 weeks of pregnancy. Those with results > or =
      135 mg/dL underwent 100-g, three-hour glucose tolerance tests. All patients
      without diagnoses of gestational diabetes during the second trimester of
      pregnancy underwent standard third-trimester glucose testing. RESULTS:
      Gestational diabetes mellitus was diagnosed in 25 patients. Glucose screening
      tests administered at 16 weeks of pregnancy identified 96% (24) of these
      patients. Patients with 16-week glucose screening test results > or = 135 mg/dL
      had a 55% risk of developing diabetes during pregnancy, while the risk was 0.6%
      for patients with 16-week test results < or = 110 mg/dL. Patients with 16-week
      glucose screening test results in the intermediate range, 111-134 mg/dL, had a
      4.8% risk of developing diabetes during pregnancy. CONCLUSION: Glucose screening
      at 16 weeks of pregnancy is a useful alternative to third-trimester screening for
      gestational diabetes. The negative predictive value of screening test results <
      or = 110 mg/dL is 99.4%. The positive predictive value for screening test results
      > or = 135 mg/dL is 55%. This latter finding is superior to the 8.6-22% found
      during the third-trimester.

PMID- 12216432
TI  - Effects of oral continuous and transdermal cyclic 17-beta estradiol and
      norethindrone acetate replacement therapy on platelet aggregation in
      postmenopausal women.
AB  - OBJECTIVE: To evaluate the effects of an oral continuous and transdermal cyclic
      17-beta estradiol and norethindrone acetate combination on platelet aggregation
      in post-menopausal women. STUDY DESIGN: Fifty postmenopausal women were randomly
      assigned to receive 17-beta estradiol and norethindrone acetate either orally
      continuously or transdermally cyclically and sequentially. Platelet counts and
      maximum platelet aggregation rates were measured before and after three months
      treatment. RESULTS: At three months there were no significant changes in platelet
      counts or in adenosine diphosphate-induced or epinephrine-induced platelet
      aggregation rates in either treatment group. CONCLUSION: Hormone replacement
      treatment with a 17-beta estradiol and norethindrone acetate combination either
      orally continuously or transdermally cyclically and sequentially does not affect
      platelet aggregation in postmenopausal women.

PMID- 12216434
TI  - Family history as a risk factor for development of uterine leiomyomas. Results of
      a pilot study.
AB  - OBJECTIVE: To determine (1) the association between maternal history of
      leiomyomas and those in women under the age of 50, and (2) the ability of
      subjects to report a family history of leiomyomas. STUDY DESIGN: We performed a
      hospital-based, case-control study. The cases were women with pathologically
      confirmed leiomyomas, and the controls were women with no leiomyomas after
      pathologic examination of the uterus or by transvaginal ultrasonography. All
      women were sent a questionnaire regarding potential risk factors for the
      development of leiomyomas. RESULTS: Eighty-one of 169 (47.9%) cases and 103 of
      214 (48.1%) of controls completed the questionnaire. By multiple logistic
      regression, significant risk factors for the presence of leiomyomas were maternal
      history (odds ratio = 2.85, confidence intervals 1.25-6.52) and reduced parity
      (odds ratio = 0.75, confidence intervals .57-.98). Increasing age was nearly
      significant as a risk factor (odds ratio = 1.07, confidence intervals 1.00-1.15).
      Of the subjects, 24% did not know the maternal history of leiomyomas, while 29%
      and > 50% were not aware of this history in a sister or grandmother,
      respectively. Extended family histories of leiomyomas could not be ascertained by
      this questionnaire-based study. CONCLUSION: Our results suggest that a maternal
      history of leiomyomas might be the largest risk factor for development of
      leiomyomas in a largely Caucasian population of women. Further studies are needed
      to better understand the possible genetic contribution to the development of
      uterine leiomyomas. Given the ascertainment bias inherent in second-hand maternal
      histories, future studies should assess maternal leiomyoma presence by
      ultrasonographic or pathologic evaluation.

PMID- 12216435
TI  - Perineal evaluation in the puerperium. Role of testing with a cotton-tipped swab.
AB  - OBJECTIVE: To verify the applicability and significance of testing with a cotton
      tipped swab in postpartum evaluation. STUDY DESIGN: One hundred seventy-eight
      puerperas were examined two months after vaginal delivery and underwent testing
      with a cotton-tipped swab, digital test, vaginal manometry and uroflowmetric
      urine stream interruption test. Statistical analysis was performed using
      Student's t test to evaluate the difference between mean values of continent and
      incontinent puerperas and the Bravais-Pearson coefficient to test the correlation
      between all the tests used in the study. RESULTS: Incontinent puerperas and
      multiparas had significantly higher swab test values than did continent and
      primiparas, who demonstrated a swab test mean value of 39.5 degrees during the
      Valsalva maneuver. The sensitivity of the swab test for stress urinary
      incontinence was 82.5%, while its specificity and positive predictive value were,
      respectively, 31.1% and 25.8%. CONCLUSION: Perineal damage occurs not only in
      symptomatic puerperas but most women. The swab test was unable to assess stress
      urinary incontinence in postpartum women, also, and demonstrated only urethral
      hypermobility. The swab test in the puerperium does not add significant
      information about pelvic floor performance and should not be used routinely
      postpartum.

PMID- 12216436
TI  - Increase in 3-methylhistidine in umbilical cord blood from acidotic fetuses.
AB  - OBJECTIVE: To examine the hypothesis that acidotic fetuses at birth have an
      increased catabolic state characterized by a negative nitrogen balance. STUDY
      DESIGN: Umbilical cord blood samples were obtained from a random, prospective
      series of fetuses at birth. Acidotic samples (pH < 7.20) were matched with
      normals (pH > or = 7.20) according to maternal and gestational age. 3
      Methylhistidine was analyzed in order to assess catabolic breakdown of muscle
      protein. RESULTS: 3-Methylhistidine was significantly increased (P < .05) in cord
      blood from acidotic fetuses when compared with controls and correlated negatively
      (P < .05) with umbilical arterial pH. CONCLUSION: Umbilical cord blood 3
      methylhistidine may be used to assess fetal nitrogen balance; acidotic fetuses
      have increased muscle catabolism.

PMID- 12216437
TI  - Hydatid of morgagni with torsion diagnosed during cesarean delivery. A case
      report.
AB  - BACKGROUND: Hydatids of Morgagni are benign, pedunculated, cystic structures
      arising from mullerian vestiges below the fallopian tube near the fimbria. They
      usually are of no clinical significance unless the pedicle becomes twisted and
      infarction occurs. CASE: A 39-year-old primigravida at 41 weeks and 5 days'
      gestation underwent primary cesarean delivery for macrosomia and failure to
      descend during labor. A 4 x 3-cm hydatid of Morgagni with torsion of the pedicle
      was found on the left fallopian tube. Ligation of the pedicle and excision of the
      infarcted cyst were performed. Histology of the specimen demonstrated cuboidal
      epithelium with extensive hemorrhage and necrosis, consistent with an infarcted
      hydatid of Morgagni. All pain and symptoms experienced by the patient during the
      previous day were associated with the onset of labor. No specific left lower
      quadrant pain was reported. CONCLUSION: Hydatids of Morgagni are common findings
      at pelvic surgery and usually of no clinical significance. Torsion of a hydatid
      of Morgagni is rarely reported and most likely is a rare occurrence. In this
      patient, torsion of the hydatid of Morgagni was possibly pregnancy related, and
      symptoms associated with torsion were probably masked by labor pain.

PMID- 12216438
TI  - Torsion of a gravid uterus associated with maternal trauma. A case report.
AB  - BACKGROUND: Torsion of the gravid human uterus is rarely encountered. Reported
      cases include uterine leiomyomata, ovarian tumors, uterine anomalies and fetal
      malpresentation as contributing factors. No case has been reported before in
      association with maternal trauma. CASE: A 20-year-old woman, gravida 2, para 1,
      presented to the emergency room at 38 1/7 weeks' gestation after being involved
      in an automobile collision. Two hours after admission, she experienced a severe,
      prolonged fetal heart rate deceleration, which was unresponsive to conservative
      measures. An emergency cesarean section was performed. Following delivery of the
      fetus, it was noted that the uterus had levorotated 180 degrees, and posterior
      hysterotomy was performed. Placental inspection disclosed a 30% abruption. The
      mother recovered uneventfully, but the infant suffered acute and long-term
      morbidity. CONCLUSION: Uterine torsion should be considered in cases of blunt
      abdominal trauma to the gravid uterus.

PMID- 12216439
TI  - Cystic fibrosis presenting as fetal anemia. A case report.
AB  - BACKGROUND: Cystic fibrosis in the fetus may present with meconium ileus, seen as
      dilated, hyperechogenic bowel on the prenatal ultrasound examination. Rarely does
      in utero bowel perforation occur with resulting peritoneal echogenicity, ascites
      or lack of bowel dilation. CASE: In a case of cystic fibrosis in a fetus, all
      three findings above occurred, as did anemia, most likely secondary to bleeding
      from perforated bowel. The anemia was detected following the finding of
      significantly elevated peak flow velocity in the middle cerebral artery (MCA).
      CONCLUSION: Fetuses with cystic fibrosis can develop anemia. MCA peak flow
      velocity measurements are helpful in detecting the anemia.

PMID- 12216440
TI  - Choriocarcinoma with diffuse intraabdominal abscess and disseminated
      intravascular coagulation. A case report.
AB  - BACKGROUND: Management of choriocarcinoma complicated by diffused intraabdominal
      abscess is difficult, especially when disseminated intravascular coagulation
      (DIC) ensues. CASE: A 29-year-old woman presented with massive vaginal bleeding,
      fever and severe abdominal pain. Choriocarcinoma with pulmonary and vaginal
      metastases was diagnosed along with diffused intraabdominal abscess. Hysterectomy
      and hypogastric artery ligation were performed after the fever and abdominal
      symptoms failed to respond to intravenous antibiotics. Although the patient
      developed DIC after surgery, transfusion, antibiotics and immediate combination
      chemotherapy improved her condition and controlled the malignancy. She was free
      of disease for > 20 months after treatment. CONCLUSION: Timely surgery,
      aggressive antibiotics and immediate postoperative chemotherapy are recommended
      for patients with choriocarcinoma complicated by intraabdominal abscess and DIC.

PMID- 12216441
TI  - In defense of the anterior vaginotomy.

PMID- 12216442
TI  - Teaching the Laufe-Piper forceps technique.

PMID- 12216443
TI  - Electronic version of the encyclopaedia of occupational health and safety as a
      source of definitions.
AB  - PROBLEM: Continuous progress in the occupational safety and health field, as well
      as social-economic development, generates a need for access to definitions.
      Definitions are usually scattered in many sources and not easy to find.
      Electronic documents give new opportunity to information access. METHOD: As an
      experiment, the feasibility of automatic full-text searching of definitions was
      examined using the Encyclopaedia of Occupational Health and Safety, edited by the
      International Labour Organization (ILO), on CD-ROM. DISCUSSION: The results were
      compared with the traditional index search by subject, using the paper version of
      the encyclopedia. The automatic search appeared successful; about 100 definitions
      were excerpted the automatic way. IMPACT ON INDUSTRY: As in most industries,
      finding accurate information is a necessity in the safety industry. The
      electronic document seems to be a powerful instrument as a source of definitions
      and can be quite easy to use by specialists as well as safety personnel in
      information processing.

PMID- 12216444
TI  - Investing in safety an analytical precautionary principle.
AB  - PROBLEM: Governments and businesses must respond to increasing safety
      requirements and balance the associated costs with productivity and competing
      pressures. METHOD: A real options approach has been introduced for decision
      making in the private sector; this approach is adapted for regulatory decisions
      that can involve irreversible and uncertain safety impacts, social costs that
      differ from private costs, and differences in perception among the stakeholders.
      RESULT AND IMPACT ON INDUSTRY AND GOVERNMENT: The outcome is an economic decision
      gage that determines if it is optimal to invest in safety even if the estimated
      costs significantly exceed the estimated benefits. Applications potentially
      include safety decisions related to aviation, ground transportation, pipelines,
      nuclear facilities, natural disaster planning, and terrorism, among others.

PMID- 12216445
TI  - Student and faculty issues in distance education occupational safety and health
      graduate programs.
AB  - PROBLEM: There is increasing interest in delivering degree programs without
      requiring students to attend traditional classroom-based classes. There are many
      differences between classroom and distance courses that must be addressed to have
      effective distance programs. METHOD: Occupational safety and health faculty and
      occupational safety and health professionals were surveyed to determine the need
      for graduate occupational safety and health programs, delivered by means of
      distance education, and the best means to deliver the program from the
      perspective of faculty and working occupational safety and health professionals.
      RESULTS: Adequate time is the largest problem issue for potential students and
      the distance student's needs must be considered when developing program policies
      and procedures. Faculty must be sufficiently trained in pedagogy, technology, and
      communications so that they have the same comfort level with this method of
      instruction as they do for the more familiar classroom, and technical and
      instructional support personnel need to be readily available to work with the
      faculty and support course development. IMPACT ON INDUSTRY: Findings indicate
      that there is interest in a distance education-based program and it is believed
      that industry will be positively impacted as educational opportunities expand for
      working professionals.

PMID- 12216446
TI  - Construction workers' falls through roofs: fatal versus serious injuries.
AB  - PROBLEM: The study examined risk factors for fatal versus serious injuries of
      construction workers' falls through roofs. METHOD: Fatal injury falls (N = 10)
      were matched against serious injury falls (N = 10), and descriptive analyses were
      carried out retrospectively of investigation reports. RESULTS: Fatal injuries
      occurred predominantly on farms, in the afternoon, and without the use of passive
      personal fall protective equipment (PPFPE; safety net, lifeline, etc.). In
      contrast, serious injuries disproportionately occurred in the morning hours, and
      were likely due to decreased risk perceptions and less safe behavior, possibly as
      the result of the greater use of PPFPE. SUMMARY: Risk factors for fatal and
      serious roof fall injury incidents differ in terms of farm/nonfarm location, time
      of day, and use of PPFPE. IMPACT ON INDUSTRY: Occupational injury incident
      surveillance systems need to collect data systematically regarding the status and
      role of personal protective equipment (PPE).

PMID- 12216447
TI  - The effect of first aid training on Australian construction workers' occupational
      health and safety motivation and risk control behavior.
AB  - METHOD: A 24-week experiment was conducted to assess how first aid training
      affects the motivation of small business construction industry employees in
      avoiding occupational injuries and illnesses and its effect on their occupational
      health and safety behavior. A simplified multiple baseline design across
      workplace settings was used to evaluate the effects of first aid training.
      Participants' motivation to control occupational safety and health risks was
      explored during in-depth interviews before and after receipt of first aid
      training. Objective measurement of occupational safety and health behavior was
      conducted by a researcher directly observing the workplace before and after
      participants received first aid training. RESULTS: The observations at
      participants' worksites suggested that, for the most part, the first aid training
      had a positive effect on the occupational safety and health behavior of
      participants. First aid training appeared to reduce participants' "self--other"
      bias, making them more aware that their own experience of occupational safety and
      health risks is not beyond their control but that their own behavior is an
      important factor in the avoidance of occupational injury and illness. First aid
      training also appeared to reduce participants' willingness to accept prevailing
      levels of occupational safety and health risk and increase the perceived
      probability that they would suffer a work-related injury or illness. Participants
      expressed greater concern about taking risks at work after receiving first aid
      training. IMPACT ON INDUSTRY: It appears that first aid training enhances
      participants' motivation to avoid occupational injuries and illnesses and
      improves their risk control behavior. The implications of this are that first aid
      training can have a positive preventive effect and could complement traditional
      occupational health and safety training programs. As such, there may be benefit
      in providing first aid training to all employees rather than limiting this
      training to a small number of designated "first aiders."

PMID- 12216448
TI  - The relationship between employees' perceptions of safety and organizational
      culture.
AB  - PROBLEM: With limited resources to help reduce occupational injuries, companies
      struggle with how to best focus these resources to achieve the greatest reduction
      in injuries for the optimal cost. Safety culture has been identified as a
      critical factor that sets the tone for importance of safety within an
      organization. METHOD: An employee safety perception survey was conducted, and
      injury data were collected over a 45-month period from a large ready-mix concrete
      producer located in the southwest region of the United States. RESULTS: The
      results of this preliminary study suggest that the reductions in injuries
      experienced at the company locations was strongly impacted by the positive
      employee perceptions on several key factors. Management's commitment to safety
      was the factor with the greatest positive perception by employees taking the
      survey. DISCUSSION: This study was set up as a pilot project and did not unitize
      an experimental design. That weakness reduces the strength of these findings but
      adds to the importance of expanding the pilot project with an appropriate
      experimental design. SUMMARY: Management leadership has been identified, along
      with several other factors, to influence employee perceptions of the safety
      management system. Those perceptions, in turn, appear to influence employee
      decisions that relate to at-risk behaviors and decisions on the job. IMPACT ON
      INDUSTRY: The results suggest that employee perceptions of the safety system are
      related to management's commitment to safety, which, in turn, appear to be
      related to injury rates. Management should focus on how to best leverage these
      key factors to more positively impact injury rates within their companies.

PMID- 12216449
TI  - Forfeiture programs in California: why so few?
AB  - PROBLEM: It is estimated that at least 75% of suspended or revoked drivers
      continue to drive illegally. In states like California, there are also a
      substantial and growing number of people who drive without ever having been
      licensed. Some states, such as Ohio and California, have enacted vehicle
      impoundment and forfeiture programs as sanctions to reduce these offenses.
      Published evaluations indicate that vehicle impoundment laws reduce recidivism
      and crash rates. However, vehicle forfeiture programs have been less successful,
      mostly because of low levels of enforcement. METHOD: Police officers and district
      attorneys from 17 jurisdictions were interviewed by phone or in person to
      determine current enforcement levels and impediments to more aggressive
      application of statutory authority. RESULTS AND DISCUSSION: The survey found that
      most California jurisdictions are enforcing vehicle impoundments for first-time
      offenders. However, very few jurisdictions were enforcing the vehicle forfeiture
      law for repeat offenders. Among the reasons for not enforcing the vehicle
      forfeiture law was a perception that it was too time-consuming and/or not a
      priority among prosecutors. However, a number of authorities indicated that the
      simple vehicle impoundment procedure is often functionally equivalent to
      forfeiture because many drivers fail to retrieve the vehicle at the end of the
      impoundment period. IMPACT ON INDUSTRY: Vehicle impoundment programs are
      effective mechanisms in deterring illicit driving, and states should be
      encouraged to initiate vehicle impoundment laws. States could achieve even
      greater safety benefits if vehicle forfeiture sanctions were extensively used for
      repeat offenders. However, based on California's experience, the incremental
      benefits of vehicle forfeiture (over vehicle impoundment) may not be very great.

PMID- 12216451
TI  - [Genomics of pathogenic bacteria].
AB  - The general principles of structural and functional organization of genomes in
      pathogenic bacteria are considered. Main data on the specific features of genomes
      of Chlamydia trachomatis, Rickettsia prowazekii, Treponema pallidum, Helicobacter
      pylori, Haemophilus influenzae, Neisseria meningitidis, Vibro cholerae and
      pathogenic strains of Escherichia coli are summarized. Particular attention is
      paid to the problems of genetic control of pathogenicity, intraspecies variations
      in bacterial genomes, to the environmental and evolutionary meaning of horizontal
      gene transfer. Whether methods for genotyping bacterial strains can be used is
      discussed.

PMID- 12216450
TI  - Organizational safety: which management practices are most effective in reducing
      employee injury rates?
AB  - PROBLEM: While several management practices have been cited as important
      components of safety programs, how much does each incrementally contribute to
      injury reduction? This study examined the degree to which six management
      practices frequently included in safety programs (management commitment, rewards,
      communication and feedback, selection, training, and participation) contributed
      to a safe work environment for hospital employees. METHOD: Participants were
      solicited via telephone to participate in a research study concerning hospital
      risk management. Sixty-two hospitals provided data concerning management
      practices and employee injuries. RESULTS: Overall, the management practices
      reliably predicted injury rates. A factor analysis performed on the management
      practices scale resulted in the development of six factor scales. A multiple
      regression performed on these factor scales found that proactive practices
      reliably predicted injury rates. Remedial measures acted as a suppressor
      variable. DISCUSSION: While most of the participating hospitals implemented
      reactive practices (fixing problems once they have occurred), what differentiated
      the hospitals with low injury rates was that they also employed proactive
      measures to prevent accidents. IMPACT ON INDUSTRY: The most effective step that
      hospitals can take is in the front-end hiring and training of new personnel. They
      should also ensure that the risk management position has a management-level
      classification. This study also demonstrated that training in itself is not
      adequate.

PMID- 12216452
TI  - [Population genetics and medicine].
AB  - The paper covers several topics that demonstrate a close relationship between
      population genetics and medicine. To study isolated populations is an effective
      tool to detect "new" Mendelian diseases and to map the genes of hereditary
      diseases. Several new molecular genetic techniques have been developed, which
      facilitates the procedure of gene mapping. New genetic polymorphisms, such as
      VNTR, STR, and SNP in particular, have increased the feasibility of searching for
      genes, which predisposes to common diseases through linkage mapping and
      association studies. DNA polymorphisms have been shown to be also effective in
      solving the problems of pharmacological genetics and for detecting genes whose
      variability is associated with the efficacy of drugs and their side effects.

PMID- 12216453
TI  - [The realm of mitochondrial genetics competence].
AB  - The paper discusses the main applications of achievements of mitochondrial
      genetics: human pathology (mitochondrial diseases, complex disease susceptibility
      genes) and population genetics (evolution of mankind, demographic history, and
      migration ways of populations). Awareness of the physiological properties of the
      well-known nucleotide sequences of mitochondrial DNA is ascertained to be a
      strategy for studying the functional organization of nuclear genome whose
      structure is all but completely decoded.

PMID- 12216454
TI  - [Regulation of face and limb development: genetic aspects].
AB  - The review presents recent and earlier data on genetic regulation of different
      morphogenetic events in diverse organisms, mainly human, murine, avian and
      Drosophila ones. Without repeating the numerous names of genes in these
      organisms, one may summarize that the sets of genes involved in the regulation of
      development of facial and limbal structures in different organisms are rather
      similar, at least overlapping to a considerable degree.

PMID- 12216455
TI  - [Impaired epigenetic gene activity regulation and human diseases].
AB  - The epigenetic (i.e. heritable states that are mediated by changes in DNA other
      than nucleotide sequence) mechanisms of regulation of gene expression have been
      recently the focus of intensive studies. Genomic imprinting refers to the
      epigenetic gene marking that results in monoallelic expression. The epigenetic
      mechanism of imprinting is based on the gamete-specific methylation of some
      mammalian genes, which restricts their expression on one of the parental
      chromosomes. The imprinted genes control fetal and placental development, cell
      proliferation and adult behavior. Changes in the normal imprinting patterns give
      rise to numerous genetic diseases, including cancer. Examining the molecular
      processes that mediate these methylation genome changes will give use a great
      insight into the mechanisms of regulation of gene activity and into the etiology
      of some human genetic diseases.

PMID- 12216456
TI  - [Comprehensive analysis of changes in critical chromosomal regions and the
      development of DNA-diagnosis protocols].
AB  - A number of genetic syndromes and cancer are caused by chromosomal
      microstructural rearrangements. It is sometimes impossible to detect this
      pathology microscopically. A complex of molecular methods makes it possible to
      detect subchromosomal deletions, point mutations, and functional anomalies on the
      respective genes, which cause a disease. Achievements of comprehensive analysis
      have been demonstrated in cases of some well-known diseases, the Prader-Willi
      syndrome, Engelmann's syndrome, the Martin-Bell syndrome, hereditary multiple
      exostotic chondrodysplasia, and retinoblastoma. DNA-diagnosis protocols are the
      result of this study.

PMID- 12216457
TI  - [Human genetics and clinical medicine].
AB  - Discoveries in biology and progress in medicine have been always exerting a
      certain influence upon the development of human genetics. The major impact of
      achievements in genetics on medicine is the design of genetic technologies that
      are widely introduced into the theoretical, clinical, and preventive sections of
      medicine. Genetic methodology brings up to date the main concepts of medicine,
      which is mostly based on current advances in genomics and human genetics acquires
      ever more a more molecular character. Genetic technologies prevent the influence
      of damaging environmental factors and the impact of changes occurring in the
      human demographic structure and gradually reduce the hereditary pathology burden
      accumulated in previous generations.

PMID- 12216458
TI  - [Organization of medical genetic service in the Russian Federation].

PMID- 12216459
TI  - [Genomics and major bioethic problems of medical genetics].

PMID- 12216460
TI  - [Variabilities in chromosomal aberrations in human somatic cells].
AB  - Variabilities in the frequency of spontaneous chromosomal aberrations depend on
      subjective and objective factors, the stochastic nature of occurrence and
      recording of the aberrations. Due to the low frequency of spontaneous chromosomal
      aberrations, it is impossible to exactly assess their frequency on an individual
      basis. The low accuracy of estimating the individual frequency of spontaneous
      chromosomal aberrations while analyzing 100-1000 cells virtually allows the use
      of the individual average frequencies of chromosomal aberrations without taking
      into account the size of a sample to have an average group estimation of the
      frequency of chromosomal aberrations. The average frequencies of spontaneous
      chromosomal aberrations can be obtained to a rather high accuracy for individual
      groups when a sample comprises 50 to several hundreds of individuals. It is shown
      that the frequency of spontaneous chromosomal aberrations does not depend on sex
      and age. There is a significant variability in their frequency in relation to a
      season and to the year of a follow-up. Regular changes are found in the frequency
      of spontaneous chromosomal aberrations depending on the number of a month and on
      the year of a follow-up.

PMID- 12216461
TI  - [Modification of a mutation process in human cells].

PMID- 12216462
TI  - [Genetic approaches to evaluating safety of human environmental factors].
AB  - Main achievements made in genetic toxicology in the past 40 years are analyzed.
      Guidelines for estimating gene toxic agents have been developed and a database
      pertaining to the mutagenicity of several thousands of chemicals has been set up.
      Experience in evaluating human mutagenic effects has been accumulated. It is
      necessary to develop a current toxicological and sanitary classification of
      mutagenic xenobiotics, to take a stock of environmental gene toxic agents by
      their activity and pollution in the areas of Russia, to work out criteria for the
      actual genetic hazards (a genetic risk) of mutagens entered the human habitat, to
      study a human individual response to mutagenes and to make "a genetic
      certification", and to analyze the feasibility of human genome protection from
      environmental mutagenic factors.

PMID- 12216463
TI  - [Some principles in the organization of cellular signaling systems: is genome an
      instructor or a performer?].
AB  - The paper outlines current views of the structural organization and dynamics of
      signalling systems in the eukaryotic cell. A cell is considered to be a dynamic
      entity with signal systems induced and reversibly formed in a certain spatial
      order and within the definite sections of a cell. The spatial and temporal
      organizations of the signalling systems are their important characteristics. The
      signalling systems provide a spatial proximity of enzymes and their substrates,
      which is critical for their efficient interaction. The signalling pathways that
      involve protein-protein interactions may represent the systems with a rather low
      free diffusion and involve binding interactions with adapter complexes,
      cytoskeletal structures and subcellular membranes. As a result, the
      "canalization" of signals can take place along the specific "tunnels" from
      membranes to the nucleus or other cellular sites. The mechanism can greatly
      facilitate the efficiency and specificity of signal transduction. Signal
      transduction is a dynamic process that causes temporal and reversible formation
      of complexes localized in certain parts of a cell. The complexes are assembled in
      response to a signal. The review considers the following: a modular principle of
      the interaction of signal proteins; principles in the anchoring of the signal
      proteins close to their interaction partners; a principle of scaffolding which
      involves the assembly of interacting components in proximity to each other and in
      a certain spatial order, thus facilitating their interaction and enhancing the
      specificity, inducibility, and reversible character of the signal systems and
      their intracellular compartmentalization, formation of networks that ensure
      crosstalks of various signalling pathways. Notions of the signal systems involved
      in the intercellular interactions and of the role of signal transduction in
      cancer progression are also presented. The complexity of signal systems and that
      of their interactions with other cellular components and of the regulations of
      signalling are discussed. In conclusion, the role of a genome in the transmission
      and expression of hereditary information is considered. It is suggested that only
      the whole cell rather than its genome is a unit that transmits complete
      hereditary information.

PMID- 12216464
TI  - [The results of 14-year cytogenetic monitoring of priority follow-up groups of
      Chernobyl accident victims].
AB  - The paper presents the results of 14-year (1987-2000) random cytogenetic
      monitoring of the Ukraine's population exposed to radiation due to the Chernobyl
      Atomic Power Plant accident. Conventional, G-banding, and molecular (FISH-WCP)
      cytogenetic methods were used to examine groups of victims exposed to radiation
      of varying intensity (reconvalescents diagnosed as having acute radiation
      disease, liquidators, Chernobyl power plant staff, and persons who had lived in
      the radionuclide-polluted areas, etc.). The examinees from all groups were found
      to have a considerable increase in the incidence of chromosomal aberrations in
      the peripheral lymphocytes as compared to their spontaneous levels. There was an
      interindividual variability in the chromosomal aberrations under identical
      radiation conditions. It was ascertained that even small human doses of long-term
      ionizing radiation could induce specific chromosomal aberrations. The findings
      show that conventional cytogenetic monitoring, and particularly by applying FISH
      and WCP methods, is an good procedure for assessing the human cell genetic
      apparatuses after radiation.

PMID- 12216465
TI  - [DNA comet assay for evaluation of genotoxic effects in risk groups].
AB  - DNA comet assay (CA), gel electrophoresis of single cells, is effective in
      evaluating the genetic (genotoxic) effects of endogenous and exogenous agents. CA
      was used to study the extent of spontaneous or UV-induced DNA damages in the
      leukocytes in two groups at genetic risk: in Chernobyl accident liquidators and
      patients with familial Mediterranean fever (FMF). There was a significant
      increase in the number of UV-induced and excision repair-mediated DNA breaks in
      both risk groups as compared to control samples. The spontaneous extent of DNA
      breaks in the cells of the liquidators and FMF patients were similar to those in
      the controls. The extent of oxidative DNA damages detected during incubation with
      the endonuclease enzymes formamidopyrimidine glycosylase and endonuclease III
      were also determined in FMF patients. There were no statistically significant
      differences in the extent of oxidative DNA damage in the cells of FMF patients as
      compared to the controls. The findings give grounds to recommend CA for
      biomonitoring of genotoxic effects.

PMID- 12216466
TI  - [Genetic and biochemical studies in occupational medicine].
AB  - Prediction of a risk for occupational diseases and their prevention should be
      made by taking into account the individual peculiarities of the body, its
      metabolism, immunity, adaptive protective mechanisms, and neurohormonal
      regulation. A study of polymorphic genetic and biochemical systems to obtain more
      data on biomarkers of susceptibility to industrial factors, their relationship to
      biochemical, immunological, and other signs is a promising line in occupational
      medicine at the present stage of its development.

PMID- 12216468
TI  - Effect of face velocity and the nature of aerosol on the collection of
      submicrometer particles by electrostatic precipitator.
AB  - Despite the electrostatic collection of aerosol particles as one of the most
      widely used air cleaning methods, there has not been sufficient amount of effort
      devoted to investigate its performance in the full range of operating conditions.
      This paper reports results of the tests of a two-stage electrostatic precipitator
      (ESP) conducted in the particle size range of 0.018-1.2 microns over a range of
      flow rates using NaCl and Environmental Tobacco Smoke (ETS) test aerosols. The
      total collection efficiency of the precipitator was found to increase with an
      increase in the count median diameter (CMD) of the particles, to have polynomial
      dependence on flow rate and no significant dependence on the type of test
      aerosol. The fractional efficiency of the precipitator was found to be dependent
      on flow rate. However, the 'critical' particle size of about 1.2 microns was
      found to exist when the fractional collection efficiency becomes independent of
      flow rate. For submicrometer particles, the collection efficiency was found to be
      independent of particle size at flow rates below 560 l/s. A minimum in the
      efficiency was observed in the 0.1-0.45 micron particle size range and for
      particles smaller than about 0.02 micron.

PMID- 12216467
TI  - Ventilation and health in non-industrial indoor environments: report from a
      European multidisciplinary scientific consensus meeting (EUROVEN).
AB  - Scientific literature on the effects of ventilation on health, comfort, and
      productivity in non-industrial indoor environments (offices, schools, homes,
      etc.) has been reviewed by a multidisciplinary group of European scientists,
      called EUROVEN, with expertise in medicine, epidemiology, toxicology, and
      engineering. The group reviewed 105 papers published in peer-reviewed scientific
      journals and judged 30 as conclusive, providing sufficient information on
      ventilation, health effects, data processing, and reporting, 14 as providing
      relevant background information on the issue, 43 as relevant but non-informative
      or inconclusive, and 18 as irrelevant for the issue discussed. Based on the data
      in papers judged conclusive, the group agreed that ventilation is strongly
      associated with comfort (perceived air quality) and health [Sick Building
      Syndrome (SBS) symptoms, inflammation, infections, asthma, allergy, short-term
      sick leave], and that an association between ventilation and productivity
      (performance of office work) is indicated. The group also concluded that
      increasing outdoor air supply rates in non-industrial environments improves
      perceived air quality; that outdoor air supply rates below 25 l/s per person
      increase the risk of SBS symptoms, increase short-term sick leave, and decrease
      productivity among occupants of office buildings; and that ventilation rates
      above 0.5 air changes per hour (h-1) in homes reduce infestation of house dust
      mites in Nordic countries. The group concluded additionally that the literature
      indicates that in buildings with air-conditioning systems there may be an
      increased risk of SBS symptoms compared with naturally or mechanically ventilated
      buildings, and that improper maintenance, design, and functioning of air
      conditioning systems contributes to increased prevalence of SBS symptoms.

PMID- 12216469
TI  - Slowly decreasing mucosal hyperreactivity years after working in a school with
      moisture problems.
AB  - In our first study in 1995, teachers, who had worked in a water-damaged school
      for more than 5 years, were tested for nasal histamine reactivity by
      rhinostereometry. They were found to have significantly increased reactivity
      compared with teachers in a school without these indoor-climate problems. This
      finding could not be explained by differences in atopy or other personal
      characteristics. In this 2-year follow-up study (1995-97), 26 of 28 teachers in
      the target school and all 18 teachers in the control school, who participated in
      the initial study, accepted to take part. They were tested with the same
      histamine provocation procedure and answered the same questionnaire as 2 years
      earlier. Technical measurements of temperature, relative humidity, dust, carbon
      dioxide, formaldehyde and total volatile organic compounds (TVOC) were carried
      out in both schools during the time period between the two test occasions. In
      this provocation test, the teachers from the repaired water-damaged school still
      demonstrated an increased reactivity to histamine compared with the teachers in
      the control school, but the difference between the growth curves of the
      provocation tests was less than in 1995. Teachers in the target school still
      complained about the indoor air quality more than their colleagues, although the
      complaints were less common. No major differences were observed in the technical
      investigation between the two schools and the measurements were all within values
      usually seen in schools in northern countries. Our conclusion is that the
      observed nasal mucosal hyperreactivity among the teachers in the renovated water
      damaged school seems to persist over years and only slowly decrease even after
      successful remedial measures have been taken.

PMID- 12216470
TI  - Subjective perceptions, symptom intensity and performance: a comparison of two
      independent studies, both changing similarly the pollution load in an office.
AB  - The present paper shows that introducing or removing the same pollution source in
      an office in two independent investigations, one in Denmark and one in Sweden,
      using similar experimental methodology, resulted in similar and repeatable
      effects on subjective assessments of perceived air quality, intensity of sick
      building syndrome symptoms and performance of office work. Removing the pollution
      source improved the perceived air quality, decreased the perceived dryness of air
      and the severity of headaches, and increased typing performance. These effects
      were observed separately in each experiment and were all significant (P < or =
      0.05) after combining the data from both studies, indicating the advantages of
      pollution source strength control for health, comfort, and productivity.

PMID- 12216471
TI  - Measurement of diffusion coefficients of VOCs for building materials: review and
      development of a calculation procedure.
AB  - The measurement and prediction of building material emission rates have been the
      subject of intensive research over the past decade, resulting in the development
      of advanced sensory and chemical analysis measurement techniques as well as the
      development of analytical and numerical models. One of the important input
      parameters for these models is the diffusion coefficient. Several experimental
      techniques have been applied to estimate the diffusion coefficient. An extensive
      literature review of the techniques used to measure this coefficient was carried
      out, for building materials exposed to volatile organic compounds (VOC). This
      paper reviews these techniques; it also analyses the results and discusses the
      possible causes of difference in the reported data. It was noted that the
      discrepancy between the different results was mainly because of the assumptions
      made in and the techniques used to analyze the data. For a given technique, the
      results show that there can be a difference of up to 700% in the reported data.
      Moreover, the paper proposes what is referred to as the mass exchanger method, to
      calculate diffusion coefficients considering both diffusion and convection. The
      results obtained by this mass exchanger method were compared with those obtained
      by the existing method considering only diffusion. It was demonstrated that, for
      porous materials, the convection resistance could not be ignored when compared
      with the diffusion resistance.

PMID- 12216472
TI  - Non-professional paint stripping, model prediction and experimental validation of
      indoor dichloromethane levels.
AB  - We have experimentally quantified exposure to dichloromethane during non
      professional paint stripping and validated the mathematical paint exposure model
      of van Veen et al. (1999). The model innovates the prediction of the
      dichloromethane evaporation rate and room concentration by accounting for
      transport in the paint stripper matrix. The experiments show that peak
      concentrations range from 600 to 1600 mg/m3, increasing to 2000 mg/m3 when direct
      sun radiation increases evaporation. A naive model prediction, using a priori
      parameter values from the experimental set-up and a previous experiment with
      alkanes, accurately predicts the upper range of the experimental values, but
      overpredicted four out of six experiments. Statistical fit of the two paint
      stripper layer parameters to the experimental data resulted in a good coincidence
      of predicted and experimental data. Model and experiment indicate that 10-30% of
      dichloromethane is immediately available for evaporation.

PMID- 12216474
TI  - [A study about normal values of urinary type IV collagen concentration--aim at
      constructing a diagnostic guideline for diabetic nephropathy].

PMID- 12216473
TI  - Association of ventilation system type with SBS symptoms in office workers.
AB  - This paper provides a synthesis of current knowledge about the associations of
      ventilation system types in office buildings with sick building syndrome (SBS)
      symptoms and discusses potential explanations for the associations. Most studies
      completed to date indicate that relative to natural ventilation, air
      conditioning, with or without humidification, was consistently associated with a
      statistically significant increase in the prevalence of one or more SBS symptoms,
      by approximately 30 to 200%. In two of three analyses from a single study
      (assessments), symptom prevalences were also significantly higher in air
      conditioned buildings than in buildings with simple mechanical ventilation and no
      humidification. The available data also suggest, with less consistency, an
      increase in risk of symptoms with simple mechanical ventilation relative to
      natural ventilation. Insufficient information was available for conclusions about
      the potential increased risk of SBS symptoms with humidification or recirculation
      of return air. The statistically significant associations of mechanical
      ventilation and air conditioning with SBS symptoms are much more frequent than
      expected from chance and also not likely to be a consequence of confounding by
      several potential personal, job, or building-related confounders. Multiple
      deficiencies in HVAC system design, construction, operation, or maintenance,
      including some which cause pollutant emissions from HVAC systems, may contribute
      to the increases in symptom prevalences but other possible reasons remain
      unclear.

PMID- 12216475
TI  - [Hypertension--special reference to kidney diseases].

PMID- 12216476
TI  - [Catabolism of brain natriuretic peptide (BNP) in normal and nephrotic rat
      kidney].
AB  - The major metabolic change that characterizes nephrotic syndrome (NS) is
      hypoalbuminemia. Edema, which is a well-recognized clinical feature, often
      results in disorder of peripheral circulation and congestive heart failure. We
      previously reported that the albumin content of kidney lysosomal proteins was
      increased more than ten-fold in nephrotic rats compared to control rats,
      suggesting that kidney lysosomes play an important role in protein degradation in
      NS. The present study was carried out to elucidate the role of catabolism of BNP,
      which is one of the functional protein-natriuretic peptides. We injected
      puromysin aminonucleoside(PAN) to induce the nephrotic rat state and isolated
      kidney lysosomes from normal and nephrotic rat kidney cortex by our methods.
      Immunoblot analysis of tricine-SDS polyacrylamide gel electrophoresis of rat
      kidney lysosomal proteins revealed the presence of an immuno-reactive peptide
      band, corresponding to the endogenous BNP. In addition, this was reduced as
      compared with the normal control. These result suggest that kidney lysosomes play
      an important role in BNP metabolism to maintain body fluid homeostasis and
      regulate blood pressure levels.

PMID- 12216477
TI  - [Low-dose cyclosporin therapy combined with prednisolone for relapsing minimal
      change nephrotic syndrome in adults].
AB  - Low-dose cyclosporin(CsA) therapy combined with prednisolone was performed in 10
      adult patients with frequently relapsing minimal change nephrotic syndrome(MCNS).
      Oral CsA was administered at the dose of 1-3 mg/kg/day(50-150 mg/day) in
      combination with preceding prednisolone(32.5 +/- 13.1 mg/day). The whole blood
      traugh concentration of CsA was maintained at the level of 50-100 ng/ml (ranging
      in 35-160 ng/ml, mean: 68.0 +/- 42.8 ng/ml), and the therapy was continued for
      31.7 +/- 12.7 months. The urinary protein excretion, serum total protein, albumin
      and total cholesterol significantly improved after treatment. The serum
      creatinine increased slightly at 3-6 months after treatment, but decreased to
      within the normal range thereafter. The frequency of relapse and the ratio of the
      complete remission period to the total observed period were compared between the
      pre-treatment period(36.6 +/- 42.5 months) and post-treatment period(31.7 +/-
      12.7 months). The frequency of relapse was significantly decreased after CsA
      treatment(2.3 +/- 1.5 times/year-->0.7 +/- 0.7 times/year, p = 0.02). The ratio
      of the complete remission period to the total observed period was increased
      significantly after CsA therapy(61.7 +/- 24.3%-->88.6 +/- 14.5%, p = 0.01). Thus,
      the low dose cyclosporin(CsA) therapy combined with prednisolone was an effective
      treatment for adult MCNS patients who relapsed frequently under conventional
      prednisolone therapy.

PMID- 12216478
TI  - [Evaluation of reticulocyte hemoglobin content, percentage of hypochromic red
      blood cells, and ratio of serum transferrin receptor level/serum iron level as
      markers of iron-deficiency erythropoiesis in patients undergoing hemodialysis].
AB  - Reticulocyte hemoglobin content(CHr), percentage of hypochromic red blood
      cells(%HRC, level of serum transferrin receptor(sTfR), and sTfR/serum iron
      ratio(sTfR/Fe) were measured in 132 hemodialysis patients. On univariate
      analysis, CHr was positively correlated with serum amyloid A(SAA) and negatively
      correlated with Kt/V. %HRC showed a positive correlation with the recombinant
      human erythropoietin(rHuEPO) dosage. The dependency of each iron-status index on
      5 variables, SAA, sFt, TS, KtN, and dose of rHuEPO administered, was determined
      by stepwise multiple regression analysis. CHr was influenced only by TS, while
      %HRC, sTfR and sTfR/Fe were influenced by both logrHuEPO dosage and TS. Patients
      whose hemoglobin concentration increased by more than 1 g/dl following iron
      supplementation were defined as Iron-Responders, and the remaining patients were
      defined as Iron-Nonresponders. Fifteen out of 20 patients responded to 10
      consecutive intravenous administrations of 80 mg of saccharated ferric oxide at
      each dialysis session, while five did not. The baseline CHr was significantly
      lower in Iron-Responders than Iron-Nonresponders. The baseline %HRC, sTfR, and
      sTfR/Fe were significantly higher in Iron-Responders than Iron-Nonresponders. The
      baseline CHr, %HRC, and sTfR/Fe were correlated with the degree of change in Hb
      concentration at 4 weeks of iron supplementation. The absolute change in CHr at 2
      weeks of iron supplementation was positively correlated with the absolute change
      in Hb concentration over the first 4 weeks. CONCLUSION: (1) In assessing the iron
      metabolic status of dialysis patients, CHr, %HRC, and sTfR/Fe were unique indices
      compared with the ordinary indices, particularly in diagnosing the functional
      iron deficiency state. (2) CHr was a valuable marker of iron deficiency anemia
      and could predict the degree of increase in Hb level following iron
      supplementation. (3) The %HRC and sTfR/Fe seemed to reflect both erythropoiesis
      induced by rHuEPO and the iron supply to erythropoietic cells.

PMID- 12216479
TI  - [The clinical evaluation of maxacalcitol on therapy for secondary
      hyperparathyroidism of chronic hemodialysis patients].
AB  - The spectrum of bone disease in end-stage renal failure is changing, but
      secondary hyperparathyroidism is still a troublesome complication. The vitamin D3
      analog, maxacalcitol, has reduced calcemic action compared to vitamin D3, but
      show equivalent suppression of parathyroid hormone(PTH) secretion. In the first
      step of the study, we investigated the severity of secondary hyperparathyroidism
      in 670 chronic hemodialysis patients, whose age, sex(male/female), and duration
      on dialysis were 63.5 +/- 12.4 years, 383/287, and 7.3 +/- 6.0 years,
      respectively. The number of patients with serum intact-PTH concentrations over
      300 pg/ml was 118. Most patients in this group(87.3%) were already being
      prescribed oral vitamin D3 analog. In the second step, maxacalcitol was
      administered intravenously, instead of the oral vitamin D3 analog, to 92 patients
      selected from the above-described group. The age, sex(male/female), and duration
      of dialysis were 59.4 +/- 11.5 years, 56/36, and 7.3 +/- 6.0 years, respectively.
      Serum intact-PTH concentration and alkaline phosphatase activity decreased
      significantly, from 612.3 +/- 32.7 to 414.2 +/- 26.8 pg/ml, and from 329.3 +/-
      17.3 to 277.0 +/- 12.5 IU/l, respectively. Serum calcium phosphorous
      concentration increased significantly, and maxacalcitol administration was
      interrupted because of hypercalcemia in 17 patients(18.5%). Serum intact-PTH
      concentration did not decrease in patients with serum Ca concentrations of 10.5
      mg/dl or more before maxacalcitol therapy. In conclusion, maxacalcitol suppressed
      PTH secretion more effectively in hemodialysis patients with secondary
      hyperparathyroidism than did oral active vitamin D3 therapy, especially in
      patients with serum Ca concentrations lower than 10.5 mg/dl.

PMID- 12216480
TI  - [A case with secondary hyperparathyroidism suggesting the direct suppressive
      effect of maxacalcitol on osteoblasts].
AB  - The direct effect of vitamin D on osteoblasts in secondary hyperparathyroidism(2
      degrees HPT) is not necessarily obvious. We found an unusual hemodialyzed patient
      without any response to oral calcitriol pulse therapy(4 micrograms x 2/week), and
      who was administered maxacalcitol at a dose of up to 15 micrograms x 3/week for
      28 months. Plasma intact parathyroid hormone(PTH) was not suppressed from the
      initial level of 1,773 pg/ml to 2,100 pg/ml. However, on the contrary, alkaline
      phosphatase(ALP) was successively suppressed from 2 weeks from the initial level
      of 1,261 IU/l to 276 IU/l. This result suggests a direct suppressive effect of
      maxacalcitol on osteoblasts in 2 degrees HPT.

PMID- 12216481
TI  - [A case of minimal change nephrotic syndrome manifesting acute renal failure in
      the course of systemic lupus erythematosus].
AB  - A 51-year-old woman with systematic lupus erythematosus(SLE) associated with
      minimal change nephrotic syndrome(MCNS) is described. The patient was diagnosed
      as SLE at 33 years of age. After steroid therapy for two years, the patient's
      course was uneventful without therapy until June 2000, when facial erythema and
      facial, pretibial edema developed. On admission, proteinuria and renal
      dysfunction were detected. Subsequently, oliguric acute renal failure developed
      and hemodialysis was started. Laboratory examination showed no significant change
      in complements and anti ds-DNA antibody levels. Renal biopsy revealed minor
      glomerular abnormalities without the deposition of immune complexes. Electron
      microscopic examination showed foot process fusion and a vacuolar change in
      glomerular epithelial cells. The diagnosis of MCNS was made and administration of
      steroid(40 mg/day) was started. Urine volume and renal function improved after 2
      weeks, and nephrotic syndrome remitted completely after 5 weeks. Although the
      association of SLE and MCNS is rare, the findings suggest that in the course of
      SLE manifesting acute ranal failure, not only lupus nephritis, but also the
      complication of MCNS should be considered.

PMID- 12216482
TI  - [A case of ANCA-associated glomerulonephritis without extrarenal symptoms with
      disease flare after starting dialysis].
AB  - A Japanese girl aged 13 years with myeloperoxidase anti-neutrophil cytoplasmic
      antibodies(MPO-ANCA)-associated glomerulonephritis(GN) progressed to end-stage
      renal failure after 7 years' clinical observation. She had been suffering from
      recurrent disease flare associated with serum MPO-ANCA elevation(i.e. 153 EU/ml,
      208 EU/ml and 358 EU/ml, maximum at each of the episodes, normal < 10 EU/ml).
      Each flare was treated successfully with prednisolone combined with
      cyclophosphamide and azathioprine. However, her renal function gradually
      deteriorated, and peritoneal dialysis(PD) was initiated 7 years after the onset
      of the disease. During the clinical course, no extrarenal manifestations were
      observed. Due to subsidence of the serum MPO-ANCA titer(10 EU/ml) after starting
      PD, prednisolone and azathioprine were tapered thereafter. Her daily urine volume
      was preserved at approximately 600 ml at that time. She suddenly developed
      fatigue with severe anemia, oliguria and hypertension 4 months after
      discontinuation of immunosuppressive therapy. The serum titer of MPO-ANCA
      increased to 100 EU/ml. These clinical observation suggests that disease flare
      may occur in selected patients with MPO-ANCA-associated GN, who develop end-stage
      renal failure requiring PD. Although recurrent flare associated with an increased
      serological activity in a proportion of patients with lupus nephritis who have
      received dialysis has been reported to date, to our knowledge, a similar clinical
      observation in the MPO-ANCA-associated GN has not been reported. Selected
      patients with the disease should be followed with close observation after
      undergoing dialysis.

PMID- 12216483
TI  - [Spiral computed tomography in the diagnosis of the abdomen gunshot wounds and
      their complications].
AB  - The results of studies by spiral computed tomography (SCT) in 62 patients with
      abdominal wounds were analyzed at the Main Military Clinical Hospital of Internal
      Forces, Ministry of Internal Affairs of Russia. The main contingent of the
      wounded included active servicemen who had been wounded in the areas of local
      conflicts, military men. The studies were conducted on days 2 to 15 of their
      receiving a wound. The potentialities of the technique in evaluating damages to
      abdominal organs, retroabdominal space, bony structures, in assessing the
      topography of foreign bodies are described. SCT was compared with classical X-ray
      and ultrasound studies, laparocentesis which are traditionally used in the
      diagnosis of gunshot injury. In the authors' opinion, SCT has become the method
      of choice in the diagnosis of gunshot injury to the abdomen and its complications
      today.

PMID- 12216484
TI  - [Assessment of 18FDG PET for diagnosis of pancreatic tumors].
AB  - The paper examines the informational value of positron emission tomography (PET)
      using 18FDG in the diagnosis of malignant of neoplasms of the pancreas and in the
      estimation of the extent of a metastatic involvement. Forty-four patients (26
      males and 18 females whose age ranged from 28 to 60 years) with histologically
      verified cancer of the pancreas were examined. The study was conducted in the
      whole body mode on an Ecat Exact 47 positron emission tomograph following 70-90
      minutes of administration of 18FDG, 370-420 MBk. To assess the findings, the
      differential accumulation ratio (DAR) of formation/liver was calculated. The mean
      DAR in patients with benign and malignant pancreatic tumors was 1.17 +/- 0.064
      and 4.90 +/- 0.3 (p < 0.05). There was a false positive case in a patient with an
      exacerbation of chronic pancreatitis in the study. A relationship was observed
      between the level of tumor tissue 18FDG capture and the degree of malignancy. PET
      scanning in the whole body mode estimates the extent of a tumorous process. The
      authors' data show that the liver was most commonly involved in a metastatic
      process (96.6%). Hence, 18FDG PET is a highly informative technique in the
      diagnosis of malignant pancreatic tumors and in the estimation of the extent of a
      metastatic process and permits a differential diagnosis between benign and
      malignant tumors.

PMID- 12216485
TI  - [Arterial chemoembolization in the combined treatment of malignant tumors of the
      tongue and maxilla: preliminary results].
AB  - The authors made a clinical evaluation of the efficiency of regional bolus
      chemotherapy and embolization as a stage of combined therapy in patients with
      inoperable cancer of the tongue and maxilla complicated by bleeding episodes.
      Carotid angiography by attempting to make chemoembolization was performed in 15
      patients. The procedure could not be done in full in 2 (13%) patients due to
      transient vascular and neurological disorders. The remaining 13 (87%) patients
      had successful chemoembolization of tumor-supplying arteries with 5-fluorouracil
      (700 mg/m2) and methotrexate (40 mg/m2) in combination with finely cut hemostatic
      sponge and fragments of metallic spirals (n = 12) or regional bolus injection of
      a cytostatic (n = 1) without arterial occlusion. After embolization, bleeding
      episodes ceased in all the patients. Full (n = 1) and partial (n = 6) responses
      to treatment or stabilization of the process (n = 5) were noted in 12 (92%)
      cases, progression was only in 1 (8%) case. The study suggests that
      chemoembolization of the branches of the external carotid artery in patients with
      cancer of the tongue and maxilla contributes to the arrest of chronic tumorous
      bleeding and to the reduction in the risk for acute A combination of systemic
      multidrug therapy, radiation therapy, and chemoembolization stabilizes a tumorous
      process in most patients.

PMID- 12216486
TI  - [Healing of "wire tunnels" in tibial diaphysis: data of local X-ray study and
      densitometry].
AB  - Fifteen pelvic extremities from adult dogs were used to perform 60 cross
      tunnelization of tibial diaphysis with a wire having a pointed groove, 1.8-mm in
      diameter, at 1,500 rpm. Thirty five leg X-ray films in the lateral projection,
      which show changes on days 30, 60, 90, 120, 520 after the experiment, were
      studied. Bony diaphysis tunnelization was found to give rise to a regeneration
      focus wherein an area of tissue element degradation and an area of introduction
      of bony fragments into soft tissues were detectable. Changes in the regeneration
      focus were determined by a response to osseous fragments, which involved the
      formation of an bony regenerate during a month and to the resorption of the bony
      matter of an osseous regenerate and osseous fragments in future. Healing of
      diaphysis defects began with the resorption of a damaged cortical layer.
      Osteogenesis prevailed at month 2 and ensured healing of cortical layer defects
      following 4-6 months.

PMID- 12216487
TI  - [Spiral computed tomography in the diagnosis of ankle and foot injuries].
AB  - The data on 187 patients with traumatic lesions of the ankle joint and foot were
      used to analyze the capacities of computed tomography (CT) in the diagnosis of
      this pathology. The efficiency of CT versus X-ray study was evaluated. Specific
      guidelines are given to make spital CT. CT is shown to be of the most informative
      value in the diagnosis of lesions of the tibial plateau, undisplaced fractures of
      the internal malleolus, small marginal comminuted fractures, and lesions of the
      distal tibiofibular syndesmosis. There is evidence for that CT plays a dominant
      role in the diagnosis of lesions of the talus and calcaneus. Emphasis is laid on
      the great value of secondary multi- and three-dimensional image reconstructions.

PMID- 12216488
TI  - [Optic coherent tomography: a new high-resolution technology of visualization of
      tissue structures. Part 1. Principle of the technique. Objects of OCT
      applications and technical decisions for their study].
AB  - The authors present a series of three papers dedicated to studies made in Russia
      in the field of optic coherent tomography (OCT), the latest noninvasive high
      resolution technology of visualization of the structure of biological tissues. A
      group of medical specialists of different disciplines has been examined over
      2,000 patients for 8 years of the use of an original class of the Russian OCT
      devices developed at the Institute of Applied Physics, Russian Academy of
      Sciences, and awarded a RF State Prize in the field of science and technology in
      1999. The first paper discusses the basic aspects of OCT, the objects of study,
      and technical decisions for the clinical application of the technique. The paper
      shows a place of OCT, whose resolving capacity is close to the cellular level
      (approximately 10-15 microns), among classical methods for imaging biological
      tissues. The optical images of different types of normal tissues and the method
      of their identification are demonstrated. It has been found that different
      optical properties of investing tissues and dentin permit their tomographic
      differentiation by showing their regular bedded structure. The tomographic
      pattern of investing tissues is affected by their specific features, such as the
      type of the lining epithelium, its keratosic processes, and the architecture of
      the basilar membrane.

PMID- 12216489
TI  - [Complex radiation diagnosis of the intrathoracic thyroid].
AB  - The study deals with a complex radiation diagnosis of mass lesions of the
      distopic thyroid. Forty five patients with mass lesions of the anterior
      mediastenum were examined. They were 28 with retrosternal and intrathoracic
      goiter, 6 with teratodermoid tumors, 11 with cysts of the anterior mediastenum. A
      complex radiation study included serial routine X-ray tomography in 2 standard
      projects, sonography, computed tomography. The diagnosis was verified on the
      basis of transthoracic and transbronchial needle biopsy with compulsory
      morphological confirmation. An intergroup comparison has shown that X-ray study
      is a screening method to detect a tumor, to define its site and its relationship
      with the adjacent organs. Ultrasound study reveals pathognomonic signs of the
      distopic goiter. Of the greatest informative value is X-ray CT which allows one
      to state about the structure of a tumor and its densitometric signs.

PMID- 12216490
TI  - [Ultrasound and X-ray urethrography and urethroscopy during endoscopic operations
      on the urethra].
AB  - In 41 patients are made x-ray ascending and descending and transrectal US (TRUS)
      of an urethrography and endoscopy before and after transurethral (TUR) of
      operations on a urethra. For 35 patients there were posttraumatic strictures and
      obliterations of a urethra, for 3--postinflammatory strictures, for 2--iatrogenic
      false courses of a urethra and for 1--congenital diverticulum of a urethra. The
      comparative estimation ultrasonic and x-ray urethrography and urethroscopy has
      shown, that they are not competitive, but complementary techniques. Thus TRUS of
      a urethra, as the technique irrelevant with radial load on the patient, can and
      should more widely be used born for primary diagnostic, and for monitoring
      outcomes TUR on a urethra.

PMID- 12216491
TI  - [Color Doppler sonography of normal male genitalia and varicocele].
AB  - The present paper reports on the results of complex sonographic examination of
      scrotum organs in 116 patients. The study was performed with Siemens sonographic
      unit. According to clinico-laboratory data and results of operative intervention,
      the patients were divided into two groups. The 1st group (8 persons) had no
      pathology in the scrotum organs, the 2nd group (98 patients) had diagnosis of
      varicocele. In norm capsular, centripetal and transmeridian arteries were
      visualized in the projection of testis in colour Doppler sonography. Resistancy
      index was measured. The group with varicocele in colour Doppler sonography with
      Valsalva test showed a prolonged retrograde wave of blood flow during the whole
      period of tension. To determine the stage of pathologic process, a scale system
      had been used. Doppler sonography enables to reveal various types of reflux. The
      character of reflux determines a pathogenetic cause of varicocele that effects on
      the choice of the method of operative intervention. Parameters of colour Doppler
      sonography allow to determine the stage of the disease and reveal subclinical
      varicocele in cases when pampiniform plexus is absent, but significant
      hemodynamic changes take place. The data of Doppler sonography have been
      confirmed by the results of operative intervention.

PMID- 12216492
TI  - [Magnetic resonance imaging in pediatric urology].

PMID- 12216493
TI  - [Radiation diagnosis in pediatrics. On the occasion of the 40th anniversary of
      the Department of Childhood Radiation Diagnosis, Russian Medical Academy of
      Postgraduate Training, Ministry of Health of the Russian Federation].

PMID- 12216494
TI  - [Radiation diagnosis of abdominal aortic aneurysms].
AB  - Four hundred and forty seven patients with aneurysms of the abdominal aorta
      (AAA), including 238 patients with aneurysmal rupture, were admitted to the
      Research Institute of Emergency Care in 1990 to 2000. The results of studies in
      225 patients (ultrasonography in 197, computed tomography in 59, and angiography
      in 104), including 155 patients with aneurysmal rupture were analyzed. Computed
      tomography (CT) has proved to be the most accurate technique in the detection and
      estimation of the size of aneurysms, as well as in the identification of ruptures
      (83.9%) and inferior to angiography (AG) in the study of involvement of the
      branches of the abdominal aorta. Ultrasound study (US) ranks below CT in its
      accuracy (US detects ruptures in 67.8%); however, US surpasses CT and AS in
      screening, particularly valuable at an admission unit and an intensive care unit,
      which permits repeated studies. AG has turned out to be the most valid method in
      identifying the involvement of renal and iliac arteries in aneurysm and in
      detecting aortocaval anastomoses; yet it is inferior to US and CT (the former
      revealed rupture and dissection in 18.6% of cases) in solving other diagnostic
      tasks. Based on the analysis, the optimal sequence of studies in the patients is
      US, CT, and AG.

PMID- 12216495
TI  - [Abundance of sea urchin Lytechinus variegatus (Lamarck) on North, East and West
      coasts of Margarita Island (Venezuela) ].
AB  - The sea urchin roe reach a very high price in the international fish product
      market favoring the increase in the catches of this resource and overfishing in
      some countries. In the Island of Margarita (Venezuela) some species, Lytechinus
      variegatus (Lamarck) among others, are consumed as food but studies to determine
      abundance of the resource are unknown. Nine sample stations (depth less than 2 m)
      on the North, East and West coast of Margarita Island were visited in six
      different occasions between February/1998 and February/1999 to study the
      population density (urchins/m2) of L. variegatus. Using a quadrat (0.25 m2)
      thrown 8 times over seagrasses (Thalassia testudinum) beds and over submerged
      rocks and the urchins removed by dive. The diameter of each specimen was measured
      and returned to the sea. The water temperature, salinity and dissolved oxygen of
      each site was measured. Were collected a total of 2,073 urchins with a diameter
      ranging from 11.0 to 84.5 mm and population density between 1 to 52 urchins/m2.
      The mean size of specimens collected in the stations was between 30.44 and 55.09
      mm and average density fluctuated between 3.2 to 43.2 urchins/m2. The station
      where sea urchins were found to be most abundant was the North coast (Manzanillo
      fishing villae) where they live on rocks with a density (38 a 52/m2) far over the
      values previously cited for the Caribbean sea and Florida.

PMID- 12216496
TI  - [Effect of hypoproteic diets enriched with essential and non-essential amino
      acids on the uninephrectomized rat ].
AB  - Hyperalimentation solutions, with low protein content but rich in amino acids,
      have been more frequently used as a dietary treatment for renal terminal
      patients, with the purpose to increase their survival. However, the literature in
      this respect is contradictory. Some authors justify the use of amino acids due to
      the fact that they seem to regenerate damaged tubular cells (glycine, for
      example). Other authors, on the contrary, do not agree with this position, since
      some amino acids, like L-Serine and Lysine, are nephrotoxic. In 1977, it was
      demostrated that Lysine and Arginine inhibited protein tubular reabsorption,
      inducing proteinuria, while Glycine, Alanine, Asparagine and Glutamic Acid did
      not. In order to clarify this issue, we carried out a controlled animal study
      using uninephrectomized rats fed during nine weeks, with different hypoproteinic
      diets (4% protein content), enriched individually with five different amino
      acids. The hypoproteinic diets were enriched with Lysine and Arginine (essential
      amino acids) and Proline, Glutamic Acid and Asparagine (non essential amino
      acids). Assays for serum biochemical markers and renal function were carried-out
      pre-nephrectomy, two weeks after nephrectomy (post-nephrectomy control) and nine
      weeks post-diet for all the animals, no matter the diet to which they were
      subjected, the serum biochemistry results showed that all the hypoproteinic
      diets, enriched with amino acids, affected the renal function. The nephrotoxicity
      of the tested amino acids, followed this decreasing order: Glutamic Acid >
      Proline > Lysine > Asparagine > Arginine. hypoproteinic diets enriched with
      Lysine, Asparagine and Arginine, produced glomerular hyperfiltration, without
      proteinuria. In summary, our results point towards the idea that, contrarily to
      what has been described in the literature by some authors: enrichment of
      hypoproteinic diets with certain amino acids does not seem to protect against
      progression of renal disease in physiologically compromised kidneys.

PMID- 12216497
TI  - Enhancement of insulin secretory response to glucose-dependent insulinotropic
      polypeptide (GIP) by growth hormone in dogs.
AB  - In the present work we examined the incretin role of gut glucose-dependent
      insulinotropic polypeptide (GIP) in the insulin over-response to meal ingestion
      found in states of hypersomatotrophism. In this context, we studied IRI secretion
      after i.v. infusion of glucose alone (0.6 g/kg/h) and also combined with GIP (0.4
      microgram/kg/h) in dogs during the control period and after subcutaneous
      administration of bovine growth hormone (bGH, 1 mg/kg), in randomized experiments
      at fortnightly intervals. Plasma levels of immunoreactive b-GH (IR-bGH) showed a
      comparable elevation at 24 h from each bGH injection. Coinciding with this rise,
      fasting plasma glucose was within the normal range and basal plasma levels of
      immunoreactive GIP (IR-GIP) remained unchanged. When GIP was given, there was a
      significant increase in IR-GIP plasma levels after 10 min of infusion, to a
      plateau near 200 pmol/l; the values were not influenced by concurrent
      administration of glucose with or without prior treatment with bGH. In the
      control observations, glucose infusion caused an insulin response area (IRA,
      pmol.min.l-1) of 3150 +/- 733. When GIP was co-infused with glucose, the IRA was
      enhanced to 6203 +/- 1380, p < 0.005. After the administration of bGH, the
      infusion of glucose alone increased the IRA to 9580 +/- 1446 (p < 0.001) and to
      15,906 +/- 2943 (p < 0.001) when GIP was co-infused with glucose. The data
      suggest that in this state of high circulating levels of growth hormone of short
      duration, the secretion of insulin in response to the stimulus of glucose alone
      and also combined with GIP is clearly enhanced. The findings therefore lend
      support for the explanation of the high insulin secretion evoked by food intake
      in growth hormone-treated dogs.

PMID- 12216498
TI  - [Immune response and anergy. Study in tuberculosis patients from the Universitary
      Hospital, Maracaibo, Venezuela ].
AB  - With the aim of evaluate the anergy in Mycobacterium tuberculosis individuals
      infected we study 57 patients and 15 healthy controls, both sex and with
      different age, which to practice Sputum Bacteriology culture (BK) and the la
      reaction intradermic with PDD. The test of tuberculine on skin was achieve
      inoculate 0.1 ml de PPD intradermic via, the results were obtained at 72 h. 28
      patient total result BK+ and 29 BK-. The Group BK+, 15 result PPD+ and 13 PPD-,
      the lastet were classify as anergic patients (BK+ PPD-). From the 29 patient
      residual (BK-), 20 was PPD+ and 9 PPD-. All the controls resulted BK- PPD-. Only
      the anergy in patient BK was evaluated + (28 individuals) patient. Was classified
      from the point of clinical view in three series: N series: 27 patient TBC+ BK-, P
      Series: 28 patient TBC+ BK+ and EP Series: 2 patient with extra pulmonary TBC.
      According to the grade of pulmonary complication, the patient separated in two
      groups, according to the extension and type of lesion found in the evaluation
      with X. rays The "group 1" with 9 patient (32.14%) it introduced lesions on one
      side with or without caverns and the "group 2" with 19 patient (67.85%) with
      bilateral lesions with or without caverns. Was carried out the Lymphoblastic
      Transformation Test (TTL) stimulating with PHA and PPD, for which patterns of
      outlying blood with heparina were gathered. The concentrations of IL-4, IL-6 and
      INF-gamma was gotten inmunoenzimatic in supernatants of cultivations for
      rehearsals and in plasm, hind to the stimulation with the PPD. The statistical
      analysis was carried out utilizing the Test T of Student in pair, Varianza
      Analysis and the square Chi. Only the controls and the patient BK-, they showed
      normal response to the PHA, in contrast, the patient BK+ PPD+ they introduced a
      suppression of the response opposite the PHA of aprox. 90%. The patient PPD+ they
      showed a superior response in cultivation that the patient PPD-. The
      concentration of IL-4 in the plasm of the anergic patient (PPD-) showed a
      significant difference (P < 0.05) with concerning the PPD group+. The
      concentration of INF-gamma was lower in the anergic patient significantly
      different to the of the patient PPD+. Similar result was gotten in the
      mensuration of IL-4 and INF-gamma in supernatants of cultivation. One could
      observe the presence of patient with IL-4+ INF-gamma, and INF-gamma or IL-4 only.
      In the patient classified clinical like series "P", the concentration of IL-4 was
      old in the "group 2" with concerning the "group 1." the opposite occurred with
      the concentrations of the INF-gamma which were old in the "group 1" (both
      differences were not significant statistical). The increase of IL-4 next to low
      concentrations of INF-gamma in anergic patient and committed clinical, it suggest
      a prevalence of the pattern Th2 (T2) in the immune response.

PMID- 12216499
TI  - Laboratory scale production of maltodextrins and glucose syrup from banana
      starch.
AB  - Banana starch was isolated to obtain maltodextrin by enzymatic hydrolysis with a
      heat-stable alpha-amylase. The maltodextrin obtained had a dextrose equivalent
      (DE) between 7-11 and showed suitable chemical characteristics for food
      application. Additionally, banana maltodextrin had a greater white color value
      and total color difference (delta E) than a sample of commercial maltodextrin.
      Further saccharification of the maltodextrins was carried out with
      amyloglucosidase and pullulanase at 60 degrees C during 24 h obtaining a glucose
      syrup. Chemical characteristics of banana glucose syrup were compared with those
      of a commercial syrup obtaining similar results. Nevertheless, the color of
      banana glucose syrup was clearer than the one of a sample of commercial syrup.
      However, it showed lower color stability than the commercial sample, i.e., the
      color of banana glucose syrup changed as a function of storage time. Banana
      starch may be used to obtain maltodextrins and glucose syrups with similar
      chemical characteristics of those obtained from maize starch. Particularly, the
      color of banana maltodextrin is adequate for its use in food products.

PMID- 12216500
TI  - [The glands of the dorso-distal mucosa of the toad Bufo marinus (Amphibia: Anura)
      tongue: histology and ultrastructure ].
AB  - Frequently, the studies on the lingual epithelium ultrastructure in anurans do
      not show differences between filiform papilae and glandular epithelia in the non
      sensory dorsal epithelium. To accomplish the study of glandular epithelium,
      samples of dorso-distalis mucosae of Bufo marinus tongue were processed for
      transmission electron microscopy and also semithin sections of the same material
      were used for light microscopy study. The results showed that the glandular
      epithelium is constituted by three different types of cells: (1) serous granular
      secretory cells; (2) mitochondria rich cells (CRM); and (3) ciliated cells.
      Detailed structures of each type of cell under light and electron microscopy were
      given. Notably, in the lingual portion studied, secretory cells showed no signs
      of exocytosis of their granules, thus suggesting that they do not have a basal or
      continuous rate of secretory activity. Additionally, the distribution,
      localization and structure of CRM in the gland epithelium suggest their
      participation in secretory cell maturation and/or function.

PMID- 12216501
TI  - [Participation of dexamethasone and E and C vitamins in the modulation of the
      hepatotoxic effect induced by fomesafen and 2,4-D amino herbicides, in rats ].
AB  - The fomesafen and 2,4-D amine herbicide induce cytotoxic effects at hepatic level
      in rats, such as: hepatomegaly, hyperplasia and increase in the enzymes activity
      which participate in the processes of peroxisomal beta-oxidation of fatty acids.
      In this work, the effect of vitamin E and C was evaluated, as well as, the
      dexamethasone in the modulation of these hepatotoxic effects. Sprague-Dawley rats
      were treated with the herbicides and with the agents to be evaluated. The
      different treatments were given during 15 days orally route. The herbicides
      combined with the dexamethasone and antioxidant agents were administrated only
      and simultaneously with the herbicides. Once concluded the different treatment,
      the rats were weighed and sacrificed. It was evaluated the liver size and liver
      fragments were obtained to determine the enzymatic activity of Fatty Acyl CoA
      oxidase (FACO) and cellular number. The results showed that the hepatomegaly
      induced by fomesafen was inhibited by the vitamins and by the dexamethasone,
      while any effect was not observed in the group of rats treated with 2,4-D amine.
      None of the agents modulated the FACO activity induced by herbicides in treated
      rats. However, the dexamethasone showed a protective effect in the hyperplasia
      induced by two herbicides. The hepatotoxic effects induced by the herbicides
      responded to a different mechanism due to the differences of the effects observed
      at the antioxidant agents. On the other hand, the inhibition of the cellular
      proliferation by the dexamethasone does not keep relation with the responsible
      mechanisms of inducing the oxidant stress into FACO activity. Under experimental
      conditions of this study, the use of these agents does not guarantee protection
      against the hepatotoxic effects induced by the herbicides.

PMID- 12216502
TI  - Heritability and correlation among some selected morphological traits and their
      relationship with fall armyworm damage in sweet corn.
AB  - Fall armyworm [Spodoptera frugiperda J. E. Smith] (FAW) is a serious pest in
      field corn and sweet corn [Zea mays L.] in many parts of the world. Sweet corn
      germplasm with effective levels of resistance to damage by the fall armyworm is
      needed to transfer resistance to commercial hybrids. The objectives of this study
      were to estimate heritability and to estimate the correlation among some selected
      morphological traits and their relationship with FAW damage. Seven shrunken-2
      (sh2) inbred lines and four commercial sh2 hybrids of sweet corn were crossed to
      Mp708, a FAW-resistant field corn line. The F2 populations were subdivided with
      one half being selected for the sh2 trait and the other half was left unselected.
      Parent, F2, and F3 populations were artificially infested with FAW and evaluated
      for leaf damage caused by FAW. Heritability estimates for FAW resistance ranged
      from 0.22 to 0.61 depending on method of estimation used. The highest
      correlations occurred between silk color and anther color (0.70) and silk color
      and glume color (0.49). There were no consistent correlations of most
      morphological traits with FAW damage. A linkage between white silk and shrunken-2
      was observed.

PMID- 12216503
TI  - [Diatoms from Unare and Piritu Lagoons, Anzoategui state, Venezuela. Subclass
      Bacillariophycidae D. G. Mann ].
AB  - The diatom flora of Unare and Piritu Lagoons, Venezuela, comprises freshwater,
      estuarine and marine organisms. In this paper, 15 species of diatoms belonging to
      the subclass Bacillariophyceae D.G. Mann are described. Water samples from Unare
      and Piritu lagoons (Venezuela) were collected from November 1988 to July 1989.
      Samples were fixed with neutral formaldehyde (10%) and were examined under phase
      contrast microscopy. Species under study were Dictyoneis marginata (Lewis) Cleve,
      Cymbella affinis (Kutzing) Cleve, Cymbella sp., Achnanthes brevipes var.
      intermedia (Kutzing) Cleve, Lyrella irroratoides (Hustedt) Mann, Navicula
      carinifera (Grunow) Peragallo, Navicula liber (W. Smith) Peragallo, Navicula
      vacillans (Schmidt) Peragallo, Navicula sp, Amphora crassa var. campechiana
      Grunow, Amphora decussata Grunow, Caloneis powelli (Lewis) Cholnoky, Tryblionella
      acuta (Cleve) Mann in Round et al., Tryblionella apiculata Gregory, Surirella
      febigerii Lewis.

PMID- 12216504
TI  - [Intracranial hypertension and brain death].

PMID- 12216505
TI  - [Propranolol protects the myocardium and prevents arterial hypotension in an
      experimental organ donation model].
AB  - OBJECTIVE: To analyze the role that sympathetic nervous system hyperactivity
      immediately following brain death plays in the cardiovascular dysfunction of an
      organ donor. MATERIAL AND METHOD: Fifteen New Zealand white rabbits were placed
      in three groups: a control group, a brain-death group without propranolol and a
      brain-death group with propranolol. Brain death was caused by severe intracranial
      hypertension; in the third group propranolol was first perfused intravenously. We
      recorded hemodynamic (heart rate, number of extrasystoles, central venous
      pressure, systemic and pulmonary arterial pressure), biochemical (adrenaline,
      noradrenaline, dopamine and troponin T) and histologic data. RESULTS:
      Catecholamine levels rose significantly in both experimental groups after brain
      death, which coincided with clinical signs of sympathetic hyperactivity in the
      group not receiving propranolol but not in the group receiving the beta-blocker.
      The myocardium of animals not receiving the beta-blocker showed myocytolysis,
      edema, subendocardial bleeding and leukocyte infiltration. Such changes were
      practically absent in the animals that received beta-blockers. In the beta
      blocker group, serum troponin, and index of myocytolysis, rose significantly less
      than in the non-premedicated group. Blood pressure in all the brain-dead animals
      was significantly lower than in the control group, but was more severe in animals
      that had not received propranolol. CONCLUSIONS: Sympathetic nervous system
      hyperactivity after brain death affects the histology and functioning of the
      myocardium in this experimental organ donor model. Pretreatment with propranolol
      prevents damage.

PMID- 12216506
TI  - [Diagnosis of brain death using trancranial Doppler ultrasonography in an
      experimental model of organ donation for transplantation].
AB  - OBJECTIVE: To create an experimental organ donor model and validate it by
      ultrasound evaluation of intracranial blood flow velocity. MATERIAL AND METHOD:
      Ten white New Zealand rabbits were assigned to either a control group or an
      experimental group. Brain death was induced in the experimental group by way of
      severe cranial hypertension. A diagnosis of brain death was based on physical
      examination and velocity of intracranial blood flow determined by transcranial
      doppler ultrasonography. Physical and ultrasound examinations were performed on
      all animals at baseline and at the time of the experiment. RESULTS: Physical
      examination and intracranial blood flow velocity were normal in the control group
      animals at baseline and during the study. The findings were also normal for the
      experimental group animals at baseline. After provocation of intracranial
      hypertension, we observed signs of brain death (absence of response to pain
      stimulus in one cranial par absence of brainstem reflexes, and apnea) in the
      experimental animals, and the velocity of flow in arteries at the base of the
      skull acquired the waveform known as sharp systolic peaks, which are
      characteristic of cerebral circulation failure. CONCLUSIONS: The results of
      physical examination and ultrasonography in this study provide adequate
      validation of this experimental model of brain death and demonstrate that
      transcranial doppler ultrasonography is useful for diagnosing brain death in the
      rabbit.

PMID- 12216507
TI  - [Effect of low-dose intravenous ketamine in postoperative analgesia for
      hysterectomy and adnexectomy].
AB  - OBJECTIVE: To evaluate the efficacy of low dose ketamine (0.15 mg/Kg i.v.) as a
      pre-emptive pain relief after general anesthesia. METHOD: Sixty-nine
      gynecological surgery patients were enrolled in this prospective, double-blind
      study. All received total intravenous anesthesia and were randomized to group A
      (n = 23) to receive preoperative ketamine, to group B (n = 23) to receive
      postoperative ketamine or to group C (n = 23) to receive placebo. A patient
      controlled anesthesia device with morphine and ketorolac was used to provide
      postoperative pain relief. We evaluated the time taken to resume spontaneous
      breathing and to administer the first analgesic dose; the pain score on a visual
      analogue scale at rest at 1, 6, 24, 48 h and on the fifth day, and upon movement
      on the first and fifth days; and morphine consumption at 6, 24 and 48 h. RESULTS:
      Recovery of spontaneous breathing occurred later in group B (10 +/- 5 min) than
      in group A (6.68 +/- 3.64 min; p < 0.05) or in group C (8 +/- 4 min). The first
      analgesic dose was infused later in group B (45.24 +/- 16.16 min; p < 0.001) than
      in group A (26.45 +/- 11.65 min) or in group C (25.47 +/- 9.19 min). The pain
      scores at rest were similar. On the fifth day, pain upon movement was less
      intense for patients treated with ketamine (group A 12 [10-21] and group B 13.5
      [2-22]) than in patients treated with placebo (group C 23 [15.5-36.75]) (p < 0.05
      group C vs. group A; and p < 0.01 group C vs. group B). Morphine consumption at 6
      h was less in group B than group C (p < 0.01). CONCLUSIONS: A low dose of
      ketamine has no preemptive analgesic effect.

PMID- 12216508
TI  - [Preoperative hemoglobin as the only predictive factor of transfusional needs in
      knee arthroplasty].
AB  - OBJECTIVE: To study transfusion requirements in total knee anthroplasty (TKA) in
      order to estimate needs and consider possible ways to improve principled
      management. PATIENTS AND METHODS: Retrospective study of all TKAs performed over
      a period of 3 months in 2000. We analyzed age, medication, hypertension,
      participation in a predeposit autologous blood program (PABP), drainage bleeding,
      transfusion requirements and hemoglobin (Hb) levels. RESULTS: One hundred ten
      TKAs were performed. Ten were excluded from analysis (2 TKA reviews, 5 patients
      with coronary artery disease and 3 with chronic bronchial diseases). We reserved
      a mean 2.46 +/- 0.5 units of packed red cells (range 2-3), and 30% of the
      patients were transfused with a mean 0.62 +/- 0.99 units (range 0-4). In 15 cases
      (50%), transfusions were not clearly indicated or were related only to the
      surgical procedure. All 5 PABP patients were transfused, but not with homologous
      blood, even through 4 had Hb levels over 9 g/dL. Only Hb level was an independent
      risk factor for transfusion. Transfusions were given to 80% of patients with Hb
      levels under 12 g/dL, to 18.8% of those with hemoglobin levels over 14 g/dL, and
      to 35.7% of those with Hb levels between 12 g/dL and 14 g/dL. CONCLUSIONS:
      Preoperative Hb level was the single predictor of transfusion in our series of
      patients. In some cases the transfusion trigger was too liberal. Alternatives to
      homologous transfusion were hardly used, with PABP applied in only 5% of the
      cases. These findings encourage us to continue trying to improve the PABP program
      and transfusion criteria, to introduce alternatives and to improve baseline Hb
      levels.

PMID- 12216509
TI  - [Epidural abscess and regional anesthesia].
AB  - An epidural abscess is a rare lesion whose consequences can cause high morbi
      mortality, particularly in obstetrics, where it occurs in young, healthy
      patients. With increased use of regional anesthesia, the incidence of epidural
      abscess will increase. We therefore review the risk factors, most common etiology
      and clinical signs, which may be non-specific but are nevertheless suggestive. We
      also review available diagnostic methods. It may be difficult to distinguish
      epidural abscess from other causes of medullar compression, but prompt diagnosis
      is essential so that emergency surgical repair can proceed and neurological
      recovery will be as early and complete as possible. Appropriate antibiotic
      therapy should be aggressive. Basic aseptic measures are critical for preventing
      infection through epidural needles, as the presence of infection at the moment of
      puncture facilitates greater susceptibility to epidural abscess.

PMID- 12216510
TI  - [Failure in the functioning of an implanted automatic defibrillator due to
      pneumothorax occurring during its implantation ].
AB  - A 67-year-old man with chronic bronchitis and coronary artery disease was
      scheduled to receive an implantable cardioverter defibrillator (ICD) after an
      episode of sustained monomorphic ventricular tachycardia. During implantation
      through the left subclavian vein, oxygen saturation decreased to slightly below
      baseline. Nevertheless, the procedure continued, given that the patient
      experienced neither breathing difficulties nor pain. When the ICD failed to
      reverse ventricular fibrillation induced to test the device, an external
      defibrillator was used. At that point, left-sided pneumothorax was observed by x
      ray. Air in the pleural cavity caused an increase in the defibrillation
      threshold. After insertion of a thoracic drain, the ICD implantation procedure
      was completed successfully.

PMID- 12216511
TI  - [Epidural hematoma after catheter removal in a patient without coagulation
      disorders].
AB  - A 69-year-old man with rectal adenocarcinoma and no relevant medical history was
      scheduled for anterior resection of the tumor under combined anesthesia. The
      epidural catheter was removed 48 h after surgery. A clinical picture consistent
      with a diagnosis of epidural hematoma developed gradually and was confirmed by
      magnetic resonance imaging. The last dose of low molecular weight heparin had
      been administered 8 h before catheter removal and blood analyses were normal.
      Recovery was complete following laminectomy and evacuation of the hematoma 31 h
      after the onset of symptoms. Our analysis of the literature on conditions leading
      to epidural hematoma after catheter insertion revealed that complications may
      appear for unknown reasons even when catheter management and thrombolytic
      prophylaxis are appropriate. Nevertheless, the maneuver for removing an epidural
      catheter is clearly not risk-free and can cause complications. Monitoring after
      removal is therefore important if complications are to be detected early.

PMID- 12216512
TI  - [Breakage of the distal portion of a double-caliber 25-29 GA Polymedic needle
      during intradural anesthesia for cesarean section].

PMID- 12216513
TI  - [Epidural analgesia with ropivacaine in the labor of a patient with corrected
      congenital transposition of the great arteries and Wolff-Parkinson-White
      syndrome].

PMID- 12216514
TI  - [Post-surgical chylothorax after bilateral cervical lymph node excision].

PMID- 12216515
TI  - [Pneumoencephaly and convulsive crises after inadvertent dural puncture in an
      obstetric patient].

PMID- 12216516
TI  - [Outbreak caused by Escherichia coli in Chalco, Mexico].
AB  - OBJECTIVE: To identify the etiologic agent responsible for a disease outbreak
      following an overflow of sewage water in Valle de Chalco, Mexico. MATERIAL AND
      METHODS: A retrospective cross-sectional study was carried out. Rectal samples
      were collected from the population of Chalco valley, who suffered from diarrhea
      and vomiting during a natural disaster that took place on May 31, 2000. The
      Instituto de Diagnostico y Referencia Epidemiologicos (Epidemic Reference and
      Diagnosis Institute, InDRE, Ministry of Health), received 1521 rectal swab
      samples from diarrhea cases, to test for E. coli strains. Statistical analysis
      was performed to find a difference of proportions between cases and non-cases
      (chi-squared test). ETEC, EIEC, EPEC and EHEC pathogenic E. coli groups were
      hybridized by colony blot. RESULTS: Strains isolated were ETEC (62.2%), EIEC
      (0.84%), EPEC (0.84%), and EHEC non-O157:H7 (0.08%); there was no hybridization
      in 36.02% of E. coli strains. Other isolated microorganisms were Salmonella spp
      (0.45%) and Shigella spp (0.06%). CONCLUSIONS: Enterotoxigenic E. coli was the
      most likely etiologic agent. Sanitary control strategies should be targeted to
      preventing outbreaks caused by this pathogenic agent. The English version of this
      paper is available at: http://www.insp.mx/salud/index.html.

PMID- 12216517
TI  - [Beliefs and knowledge of a group of doctors about the nutritional management of
      the child with acute diarrhea].
AB  - OBJECTIVE: To identify the beliefs and knowledge of a group of rural physicians
      on the dietary management of children under five years of age, with acute
      diarrhea. Physicians' dietary management was compared with that recommended by
      the World Health Organization. MATERIAL AND METHODS: A cognitive anthropology
      study was carried out from July to December 1998, on ten physicians that care for
      the infant population ascribed to Hospital Rural IMSS-Solidaridad of San Juanito
      Bocoyna, Chihuahua, Mexico. Data were collected through focus groups, case
      vignettes, free listing, pile sorting, and a semi-structured questionnaire, and
      then cross-referred. RESULTS: The physicians recognized the negative impact of
      diarrhea on the nutritional state of the child, but not all of them evaluated
      this state. Prevailing interventions were antibiotic therapy, fluid management,
      and feeding recommendations. Among the latter, the most consistent were
      breastfeeding, delayed feeding, and gradual feeding. CONCLUSIONS: The obtained
      information is in conflict with WHO's recommendations, specially with that of
      sustained feeding. The English version of this paper is available at:
      http://www.insp.mx/salud/index.html.

PMID- 12216518
TI  - [Impact of diet on the induction of infection with Giardia lamblia cysts in
      Sprague-Dawley rats].
AB  - OBJECTIVE: To assess the effect of malnutrition on the development of giardiasis
      in Sprague-Dawley rats, using different inoculum sizes of Giardia lamblia cysts.
      MATERIAL AND METHODS: An experimental study was conducted between 1995 and 1999
      at Centro de Investigacion, Alimentacion y Desarrollo (Center for Research, Food,
      and Development), in Hermosillo, Sonora, Mexico. The study population consisted
      of two groups of six to eight experimental units that were fed two different
      diets and inoculated five different concentrations of Giardia lamblia cysts. Data
      were collected on excretion of cysts, weight gain, food intake, bowel contents,
      and macro and microscopic lesions in the intestinal mucosa. Statistical analysis
      consisted of analysis of variance and residuals. RESULTS: Animals fed with a diet
      meeting nutritional requirements required an infecting inoculum of 60 cysts,
      while malnourished rats required only six cysts to develop mucosal lesions.
      CONCLUSIONS: Weight gain monitored during ten days was not a good indicator of
      Giardia lamblia infection. Infection depended on cyst inoculum size as well as on
      the nutritional status of the tested animals. The English version of this paper
      is available at: http://www.insp.mx/salud/index.html.

PMID- 12216519
TI  - Characteristics of specific reading disability in children from a
      neuropsychological clinic in Mexico City.
AB  - OBJECTIVE: This report describes the main clinical features associated with
      specific reading disability (RD) in a group of 778 school-age children studied in
      a Neuropsychological Clinic in Mexico City. MATERIAL AND METHODS: The study was
      performed retrospectively, using data abstracted from clinical records of
      subjects seen in 1995-1996. Children were mainly from low and middle economic
      strata and aged between 6 to 12 years. The following data were collected: age,
      gender, diagnosis, school grade, food intake, maternal complications during
      pregnancy, perinatal and postnatal neurological risk factors, and neurological
      signs and handedness. RESULTS: Subjects with RD had a mean age of 102.9 months,
      were predominantly male (male female ratio, 2:1). Among the study group, 49.1% of
      the children were diagnosed with RD of a visuo-sensory-motor type, and 75.1% were
      from early school years (1st to 3rd grades); 27.6% showed evidence of
      malnutrition. A previous history of language disorders (49.2%), and a high
      frequency of perinatal risk factors and neurological soft signs were also found.
      CONCLUSIONS: This study shows that variables such as gender, food intake, and
      genetic and neurological risk factors, were associated with reading disabilities
      in school children. The English version of this paper is available too at:
      http://www.insp.mx/salud/index.html.

PMID- 12216520
TI  - [Utility of studying feces for the diagnosis and management of infants and
      preschool children with acute diarrhea].
AB  - OBJECTIVE: To analyze the results of a stool work-up protocol in a series of
      infants and preschoolers with acute diarrhea. MATERIAL AND METHODS: A cross
      sectional descriptive study was conducted between April 1999 and March 2000,
      among 288 children seen at a pediatric office in Guadalajara, Mexico. The mean
      age (+/-/SD) was 23.1 +/- 13.9 months; 43% were females. Data were collected on
      demographic and clinical characteristics. The stool work-up consisted of fresh
      smear and methylene blue and Kinyoun smears, as well as determination of pH and
      reducing substances. Stool culture was performed in samples with > or = 3
      leukocytes/microscopic field and rotavirus antigen detection only in selected
      cases. Data were analyzed using descriptive statistics, chi 2, odds ratios, and
      95% confidence intervals. RESULTS: Enterophatogens (%) identified were: rotavirus
      47.1, Campylobacter jejuni 27.4, Salmonella spp. 5.1, Shigella spp. 4.3,
      Cryptosporidium parvum 2.8, Giardia lamblia 2.4, Blastocystis hominis 1.4,
      Entamoeba histolytica 0.7. An OR of 5.7 was obtained for isolation of
      enteroinvasive bacteria in the presence of fecal leukocytes. Lactose intolerance
      was detected in 19.1%. The frequencies of rotavirus antigen identification and
      lactose intolerance were significantly higher in infants; the OR for lactose
      intolerance in infants with rotavirus was 21. Mucus and blood in the stools were
      associated to enteroinvasive bacteria and Cryptosporidium parvum. CONCLUSIONS:
      The current stool work-up protocol allowed the identification of enteropathogenic
      parasites, rotavirus and lactose intolerance in a short period of time.
      Leukocytes in stools were associated to the isolation of enteroinvasive bacteria.
      The frequency of agents associated to diarrheal disease was similar to that from
      other national studies. This stool work-up protocol could be useful as a tool to
      limit the unnecessary prescription of drugs and to follow universal
      recommendations for dietary management of these patients. The English version of
      this paper is available at: http://www.insp.mx/salud/index.html.

PMID- 12216521
TI  - Design and methods of the evaluation of an HPV-based cervical cancer screening
      strategy in Mexico: The Morelos HPV Study.
AB  - OBJECTIVE: The purpose of this paper is to describe the design and methodology of
      the Morelos HPV Study. The main objective of this study is to examine the use of
      two different methods for obtaining HPV DNA specimens, self-collected vaginal and
      clinician-collected cervical, to detect pre-invasive cervical lesions and cancer.
      MATERIAL AND METHODS: This study was conducted within the regular population
      based framework of the Mexican Institute of Social Security (IMSS) cervical
      cancer screening program in Morelos. A total of 7,868 women were recruited
      between May and October 1999 and are representative of the population of women
      attending cervical cancer screening services at the 23 IMSS clinics in the state
      of Morelos in 1999. Women were provided with a detailed description of the study
      before signing an informed consent form. Basic data were obtained from all
      participants using a standard IMSS registration form. During the initial
      recruitment visit, a randomly selected subsample of 1,069 participants were
      interviewed to collect additional information about cervical cancer risk factors,
      acceptability of the HPV and Pap tests, as well as patient costs. Before the
      pelvic exam, participants were asked to provide a self-collected vaginal specimen
      for HPV testing. All participants underwent a pelvic examination that involved
      collecting a cervical sample for the Pap smear and a clinician-collected HPV
      specimen. Data were evaluated from 7,732 women with complete information for the
      three tests. The 1,147 women who received at least one positive result (Pap, self
      and/or clinician-HPV tests) were invited to return for a colposcopic
      examination. During colposcopy, biopsies were taken as appropriate, to
      histologically confirm a diagnosis of cervical intraepithelial neoplasia (CIN)
      2/3 or invasive cancer. A total of 1,015 women attended colposcopy, and 101 women
      received a histologically-confirmed CIN 2/3 or cervical cancer diagnosis.
      CONCLUSIONS: The initial enrollment activities of the Morelos HPV study are the
      basis for a prevalent case-control study and a prospective cohort study that will
      investigate the natural history of HPV infections and determine if an HPV-based
      screening strategy is a safe and cost-effective alternative to Pap screening. The
      English version of this paper is available too at:
      http://www.insp.mx/salud/index.html.

PMID- 12216523
TI  - [Evaluation of the quality of life].
AB  - This paper reviews the methods and principles for quality of life assessment. The
      aging of the population and the improved survival of people with acute and
      chronic conditions have produced several levels of disability requiring long-term
      treatment and rehabilitation. In 1948 the World Health Organization defined
      health as not merely the absence of disease but rather a state of complete
      physical, mental, and social well being. This term evolved from its conceptual
      definition to the development of scales to measure the quality of life beyond
      physical status. Thus, quality of life assessment includes areas such as mental
      health, social support, and life satisfaction. It is recognized that the
      expectations, vitality, pain, disability, and personal experiences influence the
      perception of a person's general health. A composite measurement aimed to
      quantify health according to physical, mental, and social well being
      simultaneously would likely find people at different points on the three
      different continua, but in the midranges of the composite. The
      multidimensionality problems and the level of subjectivity involved in the
      assessment of the quality of life require valid and reliable instruments. This
      paper present an inventory of 126 questionnaires aimed to measure the quality of
      life for several diseases and populations. A better understanding of the methods
      to assess the quality of life will allow the incorporation of these instruments
      in the comprehensive assessment of patients, into clinical trials, and for health
      services research. The English version of this paper is available at:
      http://www.insp.mx/salud/index.html.

PMID- 12216522
TI  - [Graphic representation of the neonatal mortality risk at a regional perinatal
      center in Merida, Yucatan, Mexico].
AB  - OBJECTIVE: To determine the neonatal mortality risk according to gestational age
      and birth weight. MATERIAL AND METHODS: The cohort consisted of 19,668 newborns
      of Centro Medico Nacional (National Medical Center) Ignacio Garcia Tellez, a
      tertiary level healthcare institution of the Instituto Mexicano del Seguro Social
      (Mexican Institute of Social Security, IMSS) of the Yucatan Peninsula. All
      newborns discharged from the hospital between January 1st, 1995 and October 31st,
      1999 were included in the study. Birth weight, gestational age, and conditions
      upon discharge were recorded. Absolute risk (AR) of mortality was calculated for
      each week-of-gestation- and birth group. RESULTS: Observed AR in newborns 34 to
      44 weeks of gestational age and weighing at least 2,250 g was 0.4, while that for
      those 26 to 32 weeks of gestational age and weighing between 1000 g was 15%.
      CONCLUSIONS: AR of neonatal mortality increased inversely proportional to
      gestational age and birth weight. These data can be used as reference values for
      our hospital and for comparison with other hospitals. The English version of this
      paper is available at: http://www.insp.mx/salud/index.html.

PMID- 12216524
TI  - ["De Morbis Artificum Diatriba." 1700-2000. ].
AB  - Bernardino Ramazzini was a renowned physician and a prolific writer, born in
      Capri in 1633. He is considered the father of occupational medicine for having
      written the first paper on workers' diseases (De morbis artificum diatriba). His
      Treaty on Workers' diseases included 53 different professions, one particular and
      specific method of analysis, and a methodological proposal to prevent these
      diseases. This essay supports the approach taken by the father of occupational
      medicine and confirms that the principles established in his work are applicable
      to this day. A fair tribute is paid to the man and his writings in the third
      century after their publication. The English version of this paper is available
      at: http://www.insp.mx/salud/index.html.

PMID- 12216525
TI  - [Indicators for evaluating health systems].

PMID- 12216526
TI  - Antiretroviral therapy 2002.

PMID- 12216528
TI  - The 2002 HIV drug guide.

PMID- 12216527
TI  - AIDS 2002: still room for improvement.

PMID- 12216529
TI  - Living with yoga.

PMID- 12216531
TI  - Drug combos.

PMID- 12216530
TI  - Microbicides: prevention tool of the future.

PMID- 12216532
TI  - New-Fill on "hold" and open-label for T-20.

PMID- 12216533
TI  - Benchmarking standards in health care subjects.

PMID- 12216534
TI  - HSE publishes review of research focusing on workplace stress measurement.

PMID- 12216535
TI  - Bibliography. Current world literature. Clinical therapeutics.

PMID- 12216536
TI  - Bibliography. Current world literature. Rheumatoid arthritis.

PMID- 12216537
TI  - Bibliography. Current world literature. Crystal deposition disease.

PMID- 12216538
TI  - Letter to the editors of the proceedings of a workshop on isolated perfused
      organs.

PMID- 12216539
TI  - Additional techniques in serous effusions.
AB  - Cytological examination is a valuable diagnostic tool in case of a serous
      effusion. The first manifestation of malignancy may be an effusion of the
      pleural, pericardial, or peritoneal cavity, especially in carcinoma of the ovary,
      or lung, and malignant mesothelioma. In other malignancies effusions may occur in
      the course of the disease. The contribution by Mother by et al. in this issue of
      ACP focuses on the contribution of image and flow cytometry to establish the
      presence or absence of malignancy in serous effusions. They point out that the
      sensitivity of DNA image cytometry in equivocal effusions may be as high as
      87.5%, and that for the detection of malignancy, DNA image cytometry is superior
      to flow cytometry.

PMID- 12216540
TI  - [Scientific misconduct].

PMID- 12216541
TI  - Professor Maurizio D'Incalci interviewed by Emma Cannell.

PMID- 12216542
TI  - The Schnitzler syndrome - a treatment at last?

PMID- 12216543
TI  - Lung embolization of prostate cancer brachiotherapy seeds: incidental finding
      during left heart catheterization.

PMID- 12216544
TI  - The intention to hasten death of terminally ill patients.

PMID- 12216545
TI  - What you need to know about your dental plan.

PMID- 12216546
TI  - The award of the "Interbrew-Baillet Latour de la Sante-2002" prize to Robert M.
      Krug for outstanding contributions to influenza virus research.

PMID- 12216548
TI  - Diversity: an answer to the nursing shortage.

PMID- 12216549
TI  - The economics of a nursing degree.

PMID- 12216550
TI  - Do we need consensus conferences?

PMID- 12216551
TI  - Page for patients. Nutritional labeling.

PMID- 12216552
TI  - Scope of neurological practice: different places, different models.

PMID- 12216553
TI  - A diffusion-weighted MRI study of acute ischemic distal arm paresis.

PMID- 12216554
TI  - Control and controllability: beliefs and behaviour in high and low expressed
      emotion relatives.
AB  - BACKGROUND: Expressed emotion (EE) is a measure of the family environment that is
      a well replicated psychosocial predictor of psychiatric relapse. Theoretical
      models of EE place heavy emphasis on the notion of control. We explored the
      extent to which high and low EE relatives made both attributions of control about
      patients and engaged in controlling behaviours. METHODS: Trained raters who were
      blind to information about EE coded interviews with 35 relatives of patients with
      schizophrenia and 42 relatives of patients with unipolar depression. Relatives
      were rated on two reliable scales that assessed relatives' tendencies to make
      illness controllability attributions and relatives' efforts to exert direct
      behavioural control over patients. RESULTS: In both the schizophrenia and
      depressed groups, high-EE relatives attributed more control to their ill family
      members than did low EE relatives. They also behaved in a more controlling
      manner. Examination of patients' clinical outcomes during a 9-month follow-up
      period revealed that high levels of behavioural control on the part of relatives
      significantly predicted relapse in patients with schizophrenia but not in
      patients with depression. CONCLUSIONS: These findings support the attribution
      based model of EE. They further suggest that controlling behaviours on the part
      of relatives may mediate the EE-relapse link in schizophrenia. Such behaviours
      may be important targets for modification in family-based interventions for
      schizophrenia.

PMID- 12216555
TI  - A life support system for satellite experiments over one year.
AB  - The study of organisms in satellites over a period of a year or longer has failed
      due, primarily, to the high technical efforts in order to keep even low organisms
      alive. A new life support system is reported which enables the performance of
      experiments over a long period of time with an approximate animal (Hirudo
      medicinalis). The system has a total weight of 3 kg and a current consumption of
      4 watts.

PMID- 12216556
TI  - [Development of integrated traditional Chinese and western medicine and change of
      medical policy in China].
AB  - "Sect of Integration of Chinese and Western Medicine" came into the world four
      hundred years ago when Traditional Chinese Medicine (TCM) contacted Western
      Medicine (WM) at the beginning of the 17th century. It collected historical
      experiences showing that the cooperation of TCM and WM is more efficient for the
      cure and prevention of disease than each of them separately. Now the recognition
      that the cooperation of eastern and western medicine is more efficient to cure
      disease is spreading widely. This study will help Korean eastern and western
      medicine to find their directions. First, the concept of "sect of Integration of
      Chinese and Western Medicine" which was established between the beginning of the
      17th century and the middle of the 20th century, and Integration of Traditional
      Chinese and Western Medicine (ITCWM) which was formed after the middle of the
      20th century will be discussed. The relationship of "sect of Integration of
      Chinese and Western Medicine" and ITCWM and political consideration for the
      establishment of ITCWM will also be discussed. Finally, the current status of
      ITCWM in China will be discussed. New trends of thought appeared in Chinese
      medicine, owing to the cultural background of modern China, the development of
      WM, and the academic background of the intellectual class. "Sect of Integration
      of Chinese and Western Medicine" and ITCWM are different in historical and social
      background. However, purpose, foundation of thoughts and logical idea are
      fundamentally the same. It can be said that "sect of Integration of Chinese and
      Western Medicine" provided academic mood to open the way for ITCWM and ITCWM is a
      succession of "sect of Integration of Chinese and Western Medicine". The concept
      of ITCWM has many ways of explanation. However, it can be said to build up the
      foundation of new medical area including Chinese special way of medical treatment
      and new methods of modern medicine, succeeding a legacy of TCM. ITCWM began
      before the establishment of People's Republic of China. Mao Ze-dong (1893-1976),
      a powerful politician, and Li Ding-ming (1881-1947) who had many experiences and
      insight for TCM and WM played important roles at this stage. The period from the
      New China to the Great Proletarian Cultural Revolution (1966-1975) is the term
      for the establishment of the shape of ITCWM. "The effort of research and
      development on TCM-WM integration" was adapted as one of hygienic policies for
      curing of epidemic disease and succession and development of the heritage of TCM
      to establish new medical area. TCM class for western medical doctors was opened
      and mass media was used to spread out ITCWM throughout China. During the period
      of the Great Proletarian Cultural Revolution, ITCWM had to be stepped back and
      stagnant. Only the TCM class of western medical doctors and some clinical
      applications were barely kept moving on and alive. From the period of the Great
      Proletarian Cultural Revolution to the end of the 1980s, there are the movement
      of re-preparation of ITCWM, education of successors, and the establishment of the
      Institute of ITCWM. Hospitals began to establish department of ITCWM.
      Furthermore, it was clearly indicated in the constitutional law that "We not only
      have to develop modern medicine but also traditional medicine". The equality of
      TCM and WM was legally established in this time. From the 1990s, "equality of TCM
      and WM" was adapted as one of the hygienic policies, and department of ITCWM was
      opened in traditional Chinese medical school and western medical school. ITCWM
      has been settled down as a new academic field through education, training,
      research, academic activity, and publishing text books. In conclusion, the motive
      of the development of ITCWM was the policy such as "the effort of research and
      development on TCM-WM integration" abd "equality of TCM and WM" aimed at the
      development of Chinese medical area. It is no doubt helpful to organize systems
      and policy-making for the cooperation of eastern and western medicine in Korea.

PMID- 12216557
TI  - Aftermath.

PMID- 12216558
TI  - A practice-based, randomized, controlled clinical trial of a new resin composite
      restorative: one-year results.
AB  - This study evaluated the performance of a low-shrinking resin composite compared
      with an amalgam for restoration of Class I and II cavities of moderate size in
      posterior teeth in a general practice setting. Fifty-two pairs of test and
      control restorations were placed in 49 patients. Clinical evaluations and
      assessments of replica models were carried out at baseline, six months and one
      year. Patients recorded their level of satisfaction with the restorations by
      means of visual analog scales. Apart from one control restoration that failed due
      to a fractured cusp, all of the restorations reviewed at six months and one year
      were intact with no unacceptable scores for any of the evaluation criteria. It
      was concluded that the resin composite evaluated, when used in conjunction with
      the recommended adhesive system, may be an appropriate alternative to amalgam in
      the restoration of posterior teeth over one year in clinical service.

PMID- 12216559
TI  - A clinical comparison of glass ionomer, resin-modified glass ionomer and resin
      composite restorations in the treatment of cervical caries in xerostomic head and
      neck radiation patients.
AB  - Controversy exists as to whether there is less secondary caries at the margins of
      glass ionomer restorations compared with other materials that do not release
      fluoride. This study examined the incidence of secondary caries for three types
      of restorative materials in Class V restorations in xerostomic patients. The
      study group consisted of 45 high caries-risk adult patients who had undergone
      head and neck irradiation for the treatment of cancer. All were substantially
      xerostomic and in need of at least three restorations in the same arch. Every
      patient received a restoration with each of the test materials, a conventional
      glass ionomer (GI), a resin modified glass ionomer (RMGI) and a resin composite
      (C). Patients were instructed in the daily use of a neutral pH sodium fluoride
      gel in custom trays. Recall appointments were made at 6, 12, 18 and 24 months,
      and the restorations were examined for material loss, marginal integrity and
      recurrent caries at the restoration margin. Fluoride compliance was determined at
      each recall period and recorded as the percentage of recommended use during that
      interval. Patients were categorized at the end of the study as fluoride non-users
      if their average compliance was 50% or less. Those with greater than 50%
      compliance were categorized as fluoride users. In the latter group, no recurrent
      caries was found for any of the restorations, whereas a material-dependent
      incidence of recurrent caries was found in the fluoride non-user group. None of
      the GI, one RMGI and eight C restorations failed due to recurrent caries. For the
      fluoride non-user patients, Fishers exact test (p=0.05) showed no statistical
      difference between GI and RMGI but statistical differences were found among those
      materials and resin composite at each recall period. Recurrent caries reductions
      for GI and RMGI relative to C were greater than 80% in xerostomic patients not
      using topical fluoride supplementation.

PMID- 12216560
TI  - Clinical evaluation of a resin-modified glass ionomer adhesive system: results at
      five years.
AB  - One hundred non-carious, non-undercut cervical lesions were restored with Silux
      Plus or Estio LC and bonded with Fuji Bond LC. The restorations were evaluated
      yearly for retention and marginal discoloration. After five years, the overall
      retention rate was 96%. Of the 41 restorations examined at five years, five had
      clinically evident marginal discoloration.

PMID- 12216561
TI  - Comparison of pulpal sensitivity between a conventional and two resin-modified
      glass ionomer luting cements.
AB  - This clinical study compared handling and any short-term tooth sensitivity
      associated with using one conventional and two resin-modified glass ionomer
      cements marketed for luting gold and ceramometal crowns. The patient's response
      to a 10-second blast of air applied to the vital tooth was scored pre-operatively
      and again within a one-to-four week post-cementation recall period. A score was
      also recorded for any sensitivity present at the time of cementation of the crown
      on the unanesthetized tooth. All three cements were easy to mix and place. Most
      of the teeth had no response to pulpal stimulation pre-operatively, associated
      with the cementation procedure or post-cementation, and there were no instances
      of severe sensitivity recorded. For all cements, the level of post-cementation
      tooth sensitivity was similar, and less than that found pre-operatively.

PMID- 12216562
TI  - Effect of self-etching primer vs phosphoric acid etchant on bonding to bur
      prepared dentin.
AB  - This study evaluated the effect of dentin conditioner on tensile bond strength to
      dentin prepared with different types of burs. A self-etching primer system, Mac
      Bond II (MB, Tokuyama Dental) and a phosphoric acid etching system, Single Bond
      (SB, 3M) were used for conditioning. Twenty-four extracted intact human molars
      were ground flat to expose occlusal dentin. After the dentin surfaces were
      polished with #600 SiC paper, the teeth were randomly divided into a control
      group and three experimental groups according to the bur grits used: #600 SiC
      paper only as the control, fine cut steel bur (SB600), crosscut steel bur (SB703)
      and regular grit diamond bur (DB) mounted in a dental handpiece utilizing water
      cooling. The dentin surfaces were treated with one of two adhesive systems, then
      composite buildups were done with Clearfil AP-X (Kuraray Medical). After soaking
      the bond specimens for 24 hours in 37 degrees C water, multiple vertical serial
      sections (0.7 mm thick, 7-8 slices per one tooth) were made, trimmed to form an
      hour-glass shape with a 1.0 mm2 cross-section and tensile bond strengths were
      determined at a crosshead speed of 1 mm/minute. Statistical analysis was made
      using one and two-way ANOVA and Fisher's PLSD test (p<0.05). Six additional
      molars were used for SEM observations of the dentin surfaces of each group before
      and after treatment with the self-etching primer of MB, and another four teeth
      were used to observe the resin-dentin interface of each group of SB. Using MB,
      the DB group produced the lowest tensile bond strength (TBS) among the groups
      that received bur preparation, and there were no statistical differences among
      SB600, SB703 and the control. For SB, the TBS of SB703 was the highest, and there
      were no statistical differences among the other groups and the control. The
      influence of the method used to prepare dentin for micro-tensile bond strength
      testing was dependent on the adhesive system used.

PMID- 12216563
TI  - Retention of selected core materials to zirconia posts.
AB  - Due to their favorable optical and mechanical properties, endodontic posts made
      of partially stabilized zirconia ceramic (ZrO2-Y2O3) are a promising alternative
      to those made of metal. Zirconia posts can be combined with various tooth-colored
      core materials to increase the optical properties of a final esthetic
      restoration. For stability, a reliable bond between core material and the post
      should be generated. This in vitro study evaluated the retention of selected core
      materials to zirconia posts dependent on different surface treatments and bonding
      procedures. Two types of zirconia posts (CeraPost [CEP], Lemgo, Germany) and
      CosmoPost [COP], Ivoclar Vivadent, Amherst NY 14228, USA) were employed for the
      study. Ring-shaped cores were fabricated of either heat-pressed, zirconia
      containing glass ceramic (IPS Empress Cosmo [EMC], Ivoclar Vivadent), highly
      filled hybrid composite (Tetric Ceram [TEC], Ivoclar Vivadent) or an
      experimental, high-strength glass ceramic (OHSU-RWTH [EX], Ivoclar Vivadent). The
      core made of material EX was either directly heat pressed (EXP) or adhesively
      bonded (EXB) onto the post using a flowable composite. Prior to core application,
      the post surfaces were preconditioned by alumina abrasion (AA) or tribochemical
      silicoating and silanation (TCS). Specimens (10 per group) were stored in
      artificial saliva (pH 5.2) for 150 days. Storage time included 5,000 thermocycles
      (5/55 degrees C per 30 seconds). Defect analysis was conducted visually using a
      light microscope and a fiber optic transillumination prior to the testing
      procedure. The loads required to separate post and core were determined by a push
      out test. Following testing, the surfaces of the posts and core materials were
      evaluated in a scanning electron microscope (SEM). There were no statistically
      significant differences between the separation loads of groups COP/AA/EMC,
      COP/TCS/TEC, CEP/AA/EMC and COP/AA/EXB. Group COP/AA/EXP showed significantly
      higher retention, but also the highest standard deviation and the highest number
      and diversity of severe defects in the core material prior to testing. Similar
      defects were detected in the group COP/AA/EXC. In group COP/TCS/TEC, where there
      were a lower number of minor defects, and in COP/AA/EMC and COP/AA/EMC, no
      defects were observed. For both post systems tested with the combinations alumina
      abrasion/zirconia-containing glass-ceramic and tribochemical silicoating and
      silanation/highly-filled hybrid composite, a reliable retention was achieved. The
      use of the experimental high-strength glass ceramic as a core material is
      contraindicated due to a discrepancy in the coefficient of thermal expansion to
      the zirconia-post.

PMID- 12216564
TI  - Surface texture of resin-modified glass ionomer cements: effects of
      finishing/polishing time.
AB  - This study compared the surface texture of resin-modified glass ionomer cements
      after immediate and delayed finishing with different finishing/polishing systems.
      Class V preparations were made on the buccal and lingual/palatal surfaces of 64
      freshly extracted teeth. The cavities on each tooth were restored with Fuji II LC
      (GC) and Photac-Fil Quick (3M-ESPE) according to manufacturers' instructions.
      Immediately after light-polymerization, gross finishing was done with 8-fluted
      tungsten carbide burs. The teeth were then randomly divided into four groups of
      16 teeth. Half of the teeth in each group were finished immediately, while the
      remaining half were finished after one-week storage in distilled water at 37
      degrees C. The following finishing/polishing systems were employed: (a) Robot
      Carbides; (b) Super-Snap system; (c) OneGloss and (d) CompoSite Polishers. The
      mean surface roughness (microm; n=8) in vertical (RaV) and horizontal (RaH) axis
      was measured using a profilometer. Data was subjected to ANOVA/Scheffe's tests
      and Independent Samples t-test at significance level 0.05. Ra values were
      generally lower in both vertical and horizontal axis with delayed
      finishing/polishing. Although significant differences in RaV and RaH values were
      observed among several systems with immediate finishing/polishing, only one (Fuji
      II LC: RaH - Super-Snap < Robot Carbides) was observed with delayed finishing.

PMID- 12216565
TI  - Changes in flexural properties of composite restoratives after aging in water.
AB  - This study evaluated the changes in flexural properties of microfill (Filtek A110
      [AO]), minifill (Filtek Z100 [ZO] and Z250 [ZT]), poly-acid modified (F2000
      [FT]), and flowable (Filtek Flowable [FF]) composites after aging in water. The
      flexural strength and modulus of the composites were determined after one week
      and one month of aging in water at 37 degrees C. Samples were prepared and tested
      according to ISO specifications. Data was analyzed using ANOVA/Scheffe's test and
      independent samples t-test at significance level 0.05. Mean flexural strength
      (n=7) ranged from 66.61 to 147.21 and 68.74 to 142.69 MPa at one week and one
      month, respectively. Mean flexural modulus (n=7) at one week and one month ranged
      from 3.45 to 11.30 and 4.76 to 13.02 GPa, respectively. ZO and ZT were
      significantly stronger than AO, FT and FF and FF was significantly stronger than
      AO & FT at both time periods. At one week and one month, AO and FF were
      significantly more flexible than the ZO, ZT and FT. In addition, ZO and FT were
      significantly stiffer than ZT. With the exception of AO, a significant increase
      in flexural modulus was observed with all composites. Although flexural strength
      of FT and FF was significantly increased with aging in water, the flexural
      strength of ZT was significantly decreased.

PMID- 12216566
TI  - Quantitative evaluation of marginal leakage of two resin composite restorations
      using two filling techniques.
AB  - This in vitro study evaluated the marginal leakage of two light-cured resin
      composites used for posterior restorations using two filling techniques.
      Standardized Class V cavities were made on the enamel vestibular surface of 30
      freshly extracted sound inferior bovine incisors. The teeth were randomly
      restored according to three experimental groups (Group 1--Z250 with 1 mm vertical
      increments; Group 2--Z250 with 1 mm horizontal increments; Group 3--SureFil with
      1 mm horizontal increments). All samples were thermocycled (3000 cycles at 5
      degrees C and 55 degrees C) with a dwell time of one minute at each temperature
      and immersed in a dye solution for 12 hours. After being ground into powder, the
      samples were individually immersed into glass tubes with absolute alcohol. The
      solution was centrifuged and the supernatant was analyzed using a
      spectrophotometer to quantify its dye concentration. Results showed that Group 2
      exhibited the lowest leakage means, which was significantly different from Groups
      1 and 3 (p<0.05). It was concluded that despite the lower leakage means exhibited
      by medium viscosity composites, no restorative material or filling technique was
      able to avoid leakage.

PMID- 12216567
TI  - Extent of the cariostatic effect on root dentin provided by fluoride-containing
      restorative materials.
AB  - This study evaluated the extent of the cariostatic effect on root dentin provided
      by four fluoride-containing restorative systems: Ketac-Fil/ESPE [Ke], Fuji II LC
      Improved/GC Corp [Fj], Dyract AP/Dentsply [Dy] and SureFil/Dentsply [Su], and one
      without fluoride: Z250/3M [control]. Ninety-five bovine root dentin fragments
      (5.0 x 6.0 mm) were obtained, embedded in polyester resin and planed. Cavities
      (1.5 x 3.5 x 1.0 mm) were made and restored by the five restorative systems
      (n=19) in a randomized complete block design according to the manufacturers'
      instructions. After 24 hours, the dentin/restoration surface was polished. The
      restoration surface and an adjacent area of 3.0 x 3.0 mm were demarcated and
      submitted to a pH-cycling model. Dentin surface Knoop microhardness values were
      obtained (5.0-g, 5.0-s) for 10 distances: 50, 100, 150, 300, 600, 900, 1200,
      1500, 1800 and 2100 microm from the margin of the restoration. The dentin
      microhardness means for each restorative material at each distance was considered
      by the ANOVA multi-factor split-plot method. The interaction between the
      restorative system and distance was statistically significant (p<0.05). The Tukey
      test and the regression analysis showed that the means of [Ke] and [Fj] were
      similar up to 300 microm, the [Ke] means being higher than the [control] at
      distances 50, 100, 150 and 300 microm. The [Fj] means were higher than the
      [control] at distances 50, 100 and 150 microm. The microhardness means of [Dy]
      and [Su] were not statistically different from the [control] and remained steady
      throughout the studied distances. This study concluded that the extent of the
      cariostatic effect on root dentin was 300 microm for [Ke] and 150 microm for
      [Fj]. [Dy] and [Su] did not show any cariostatic effect.

PMID- 12216568
TI  - Survival analysis of posterior restorations using an insurance claims database.
AB  - This study indicates that composite restorations do not last as long as amalgam
      restorations in posterior teeth. Dentists can use this information to better
      inform their patients when choosing restorative materials.

PMID- 12216569
TI  - Micromorphological study of resin-dentin interface of non-carious cervical
      lesions.
AB  - This study examined the interfaces between two dentin adhesives, namely, One Coat
      Bond, Clearfil SE Bond and a resin-modified glass ionomer cement (Fuji II LC) and
      the dentin of non-carious cervical lesions (NCCLs) with FE-SEM, and compared them
      with the interfaces produced with "normal" dentin. Fifteen human premolars each
      with a buccal NCCL were used. Cervical cavities were prepared on the lingual
      surface of the same teeth for the normal (control) dentin. All lesions and
      prepared cavities were cleaned with a slurry of pumice and water. The teeth were
      randomly divided among the three products that were applied according to the
      manufacturers' instructions. For the resin-bonded specimens, the cavities were
      restored with resin composite. All specimens were stored in 37 degrees C tap
      water. Resin-bonded specimens were observed using FE-SEM after treatment with 10%
      phosphoric acid, and 10% phosphoric acid and 5% sodium hypochlorite (NaOCl). The
      resin-modified glass ionomer cement (RM-GIC) specimens were observed after 10%
      phosphoric acid and 5% NaOCl treatment. The hybrid layer could be observed for
      the two adhesive systems in all specimens, but the thickness varied depending on
      the bonding system used and the dentin substrate. The results suggested that the
      hybrid layer produced in normal dentin was slightly thicker than that of NCCLs.
      Further, the hybrid layer thickness decreased in all specimens after NaOCl
      treatment.

PMID- 12216570
TI  - Marginal and internal adaptation of stratified compomer-composite Class II
      restorations.
AB  - Different approaches have been proposed to improve the adaptation of Class II
      restorations, including applying low-elasticity modulus base liners. This in
      vitro fatigue test (or study) evaluated the influence of the compomer base-lining
      configuration on restoration adaptation. Direct Class II MOD box-shaped composite
      restorations with or without base and lining (n=3x8) were placed on intact human
      third molars with proximal margins 1 mm above or under the CEJ. The compomer
      (Dyract) was applied as a 1 mm-thick lining or as a base, closing proximo
      gingival margins. Marginal adaptation was assessed before and after each phase of
      mechanical loading (250,000 cycles at 50N, 250,000 cycles at 75N and 500,000
      cycles at 100N); internal adaptation was evaluated after test completion. Gold
      sputtered resin replicas were observed in the SEM and restoration quality
      evaluated in percentages of continuity (C) at the margins and within the internal
      interface after sample section. Mechanical loading did not influence adaptation
      to enamel, while it adversely affected restoration adaptation to dentin for the
      full composite and compomer-base restorations (C varied, respectively, from 95.2
      to 75.3% and from 98.0 to 10.6%). The internal adaptation quality showed the same
      general trend, however, with reduced scores of continuity. In this experimental
      condition, application of a low elasticity modulus layer under the restorative
      material proved advantageous but the compomer should not contact the gingival
      margins.

PMID- 12216571
TI  - Guidance of shrinkage vectors vs irradiation at reduced intensity for improving
      marginal seal of class V resin-based composite restorations in vitro.
AB  - This study evaluated the influence of radiation intensity on polymerization of a
      resin-based composite (RBC) and compared the influence of guidance of shrinkage
      vectors vs irradiation at reduced light intensity on the marginal seal of Class V
      RBC restorations in vitro. The degree of cure was studied indirectly by measuring
      the Vickers hardness (1.96 N, 30 seconds) at the bottom of disc-shaped specimens
      2 mm in height at different periods of time after light irradiation. After one
      hour, irradiation using a high-intensity curing light (Heliolux GTE, Vivadent,
      600 mW/cm2) [HICL] from close distance for 20 seconds, 40 seconds or 60 seconds
      or a low-intensity curing light (Vivalux, 250 mW/cm2) [LICL] from close distance
      for 60 seconds produced higher hardness values compared to 20 seconds or 40
      seconds using the LICL or using the HICL from a distance of 10 mm. After three
      and 24 hours, higher hardness was observed for all irradiation protocols. After
      24 hours, only specimens irradiated by the HICL for 20 seconds or 40 seconds from
      10 mm distance featured significantly lower hardness compared to the remaining
      curing modes. The influence of different irradiation strategies on marginal seal
      of Class V RBC restorations was evaluated in vitro using dye penetration after
      water storage (60 days, 37 degrees C) and thermocycling (2500 cycles 5 degrees-55
      degrees C). The HICL produced more dye penetration than the LICL. Placing the
      light tip directly over or 10 mm above the center of the cavity ("standard
      irradiation, ["distance irradiation"]") resulted in similar penetration values.
      In contrast, positioning the light tip apical to the cervical margin and moving
      it slowly to the center of the cavity ("cervical start irradiation") compromised
      the marginal seal.

PMID- 12216573
TI  - Technique on restoring cervical lesions.
AB  - This paper describes a technique of placing a semi-rigid cervical matrix slightly
      past the cervical border of a lesion that extends below (apical to) the gingival
      crest and inserting the glass ionomer cement through an opening cut in the matrix
      above the soft tissue level.

PMID- 12216572
TI  - The influence of a packable resin composite, conventional resin composite and
      amalgam on molar cuspal stiffness.
AB  - Packable resin composites may offer improved properties and clinical performance
      over conventional resin composites or dental amalgam. This in vitro study
      examined the cuspal stiffness of molars restored with a packable resin composite,
      a conventional posterior microfilled resin composite and amalgam. Forty-eight
      intact caries-free human third molars were distributed into four treatment groups
      (n=12) so that the mean cross-sectional areas of all groups were equal.
      Standardized MOD cavity preparations were made and specimens restored using one
      of four restorative materials: (1) a spherical particle amalgam (Tytin); (2)
      Tytin amalgam with a dentin adhesive liner (OptiBond Solo); (3) a conventional
      microfilled posterior resin composite (Heliomolar); (4) a packable posterior
      resin composite (Prodigy Posterior). Cuspal stiffness was measured using a Bionix
      200 biomaterials testing machine (MTS). Specimens were loaded vertically to 300 N
      at a crosshead speed of 1.0 mm/minute. Stiffness was measured at 10 intervals:
      (1) prior to cavity preparation (intact); (2) following cavity preparation, but
      before restoration; (3) seven days after restoration; then (4) 1, 2, 3, 4, 5, 6
      and 12 months after restoration. All specimens were stored at 37 degrees C in
      deionized water throughout the study and thermocycled (5 degrees/55 degrees C;
      2000 cycles) monthly for 12 months. Repeated Measures ANOVA revealed significant
      differences among treatment groups over time (p<0.0001). Cavity preparation
      reduced cuspal stiffness by more than 60%. At 12 months, the cuspal stiffness of
      restored teeth was, on average, 58% that of intact specimens. Neither the
      packable nor the conventional resin composite increased cuspal stiffness over
      that of amalgam.

PMID- 12216575
TI  - The prince and the pauper.

PMID- 12216574
TI  - Failure, repair, refurbishing and longevity of restorations.
AB  - The clinical diagnosis of secondary caries is the main reason for replacement of
      all types of directly-placed restorations. This is an ill-defined clinical
      diagnosis both in teaching programs and in general practice. The criteria for the
      diagnosis must be improved and come in line with those for primary caries.
      Secondary caries are usually localized and delineated lesions and should be
      differentiated from stained and ditched margins. Small defects of secondary
      caries, stained and degraded margins may be removed by refurbishing/refinishing
      procedures. Larger defects may be explored by removing part of the restoration to
      access the defective margin. By removing part of the restoration to the full
      depth, a firm diagnosis can be made regarding the extent of the lesion, as the
      defects are often well delineated. Provided the main part of the restoration is
      satisfactory, the "exploratory" cavity preparation can then be filled with an
      appropriate material. These approaches will save tooth structure and be cost
      effective. However, longevity data are lacking with such studies in progress.

PMID- 12216576
TI  - Erectile-dysfunction therapies.

PMID- 12216577
TI  - Emerging unscathed?

PMID- 12216578
TI  - The erosion of employer-based health coverage and the threat to workers' health
      care: findings from The Commonwealth Fund 2002 Workplace Health Insurance Survey.

PMID- 12216579
TI  - Someday everyone will be a chemist.

PMID- 12216580
TI  - Tabletop fusion revisited.

PMID- 12216581
TI  - Documenting Lysenkoism.

PMID- 12216583
TI  - Moral questions, legal answers, and biotechnological advances.
AB  - Moral failing is usually construed as a personal flaw, but there is another
      construction: where morals fail people, where our moral precepts are silent. The
      author of this article argues that this happens nowadays where technological
      advances, such as genetic engineering in medicine, raise moral questions but get
      legal answers. By responding to the legal issues involved, the moral questions
      are pre-empted. This results in answers drawn from legal categories, often with
      commercial perspectives, but misses the larger moral dilemma.

PMID- 12216582
TI  - The moral case for the legalisation of voluntary euthanasia.
AB  - If a person is suffering from illness or disability and wishes to end their life
      the law ought to facilitate rather than frustrate that choice argues Graham Oddie
      in this article. He points out the inconsistencies in current medical practice,
      and the gross disparity between the practice and the letter of the law. In
      dismissing many of the commonly raised objections to calls for reform of the law
      permitting euthanasia he makes a strong case for consistency in our approach to
      the right to die and patient autonomy.

PMID- 12216584
TI  - Occupational dermatoses from photographic chemicals.

PMID- 12216585
TI  - Using a filter bypass leakage test for aerosol sampling cassettes.

PMID- 12216586
TI  - Fire fighter deaths from tanker truck rollovers.

PMID- 12216587
TI  - Carbon monoxide exposure from coffee roasting.

PMID- 12216588
TI  - Work and health country profiles and national surveillance indicators in
      occupational health and safety.

PMID- 12216589
TI  - Environmental endotoxin measurement methods: standardization issues.

PMID- 12216590
TI  - Test-retest reliability of a self-administered musculoskeletal symptoms and job
      factors questionnaire used in ergonomics research.
AB  - The purpose of this study was to investigate the test-retest reliability of
      questionnaire items related to musculoskeletal symptoms and the reliability of
      specific job factors. The type of questionnaire items described in the present
      study have been used by several investigators to assess symptoms of
      musculoskeletal disorders and problematic job factors among workers from a
      variety of occupations. Employees at a plastics molding facility were asked to
      complete an initial symptom and jobs factors questionnaire and then complete an
      identical questionnaire either two or four weeks later. Of the 216 employees
      participating in the initial round, 99 (45.8%) agreed to participate in the
      retest portion of the study. The kappa coefficient was used to determine
      repeatability for categorical outcomes. The majority of the kappa coefficients
      for the 58 questionnaire items were above 0.50 but ranged between 0.13 and 1.00.
      The section of the questionnaire having the highest kappa coefficients was the
      section related to hand symptoms. Interval lengths of two and four weeks between
      the initial test and retest were found to be equally sufficient in terms of
      reliability. The results indicated that the symptom and job factors questionnaire
      is reliable for use in epidemiologic studies. Like all measurement instruments,
      the reliability of musculoskeletal questionnaires must be established before
      drawing conclusions from studies that employ the instrument.

PMID- 12216591
TI  - A field comparison of the IOM inhalable aerosol sampler and a modified 37-mm
      cassette.
AB  - This research focused on comparing a modified 37-mm (Mod37) sampling cassette
      with an IOM inhalable dust sampler. Paired IOM and Mod37 breathing-zone air
      samples were collected for workers engaged in corrosion control maintenance
      operations on several types of aircraft at several U.S. Air Force bases in the
      United States. Sampled operations included hand and power sanding, blow-down and
      wipe-down to remove dust, and spray finishing. The cassettes' interior surfaces
      were swabbed and the swabs combined with the filters for chromium analysis by
      NIOSH Method 7300. This approach utilized total chromium as a sensitive surrogate
      indicator of total aspirated mass. The influences of work location, work type,
      sample duration, and sampler type on measured concentration were evaluated using
      analysis of variance techniques. Only work type (process) was found to be a
      statistically significant predictor of measured concentration. The relationship
      between IOM- and Mod37-measured values for paired samples was evaluated by work
      type using linear regression techniques. Linear regressions showed that the
      modified 37-mm cassette over-samples aerosol by 35 percent compared to the IOM
      when a wide range of aerosol concentrations and compositions for divergent work
      tasks in multiple field locations are sampled. Interpretation of these results in
      light of previous results involving filter-only Mod37 analyses suggests that
      while the Mod37 has a higher aspiration efficiency than the IOM, substantial
      Mod37 wall losses result in underestimation of exposure when only the 37-mm
      filter is analyzed rather than filters plus wall swabs.

PMID- 12216592
TI  - Prevalence and location of teeth marks observed on painted surfaces in an
      evaluation of the HUD lead hazard control grant program.
AB  - Data from an evaluation of the HUD Lead Hazard Control Grant Program were used to
      evaluate the prevalence and location of teeth marks on painted surfaces in
      residential housing. The results of these analyses will be useful in the
      development of more effective pediatric lead poisoning prevention programs. These
      programs have historically placed considerable emphasis on surfaces accessible to
      children for mouthing activities. This study analyzes the largest set of data
      ever assembled on the prevalence of teeth marks in housing. Data from 308,851
      observations in 3,454 housing units were analyzed to determine the prevalence of
      teeth mark observations per surface, dwelling unit, and building component, and
      by housing age, inspector, and grantee. An average of 4.0 teeth marks per 10,000
      surfaces with paint-lead greater than or equal to 1.0 mg/cm2 were observed. For
      surfaces with less than 1.0 mg/cm2 lead the rate was 1.5 teeth marks/10,000
      surfaces. The number of teeth marks per 10,000 surfaces increased with age of
      housing for surfaces with 1.0 mg/cm2 or higher lead but not for surfaces with
      less than 1.0 mg/cm2 lead. Teeth mark observation rates were 36 times higher for
      windowsills than for other components and ranged up to 11 per 10,000 surfaces and
      9 dwellings per 100 dwelling units for 2 grantees with the highest rates. Blood
      lead levels in children exhibiting moderate to high mouthing behavior were higher
      than in children without such behavior, especially in housing where teeth marks
      were observed. Special priority should be given to windowsills when making
      decisions on lead hazard control for "accessible," "chewable," or "mouthable"
      surfaces.

PMID- 12216593
TI  - Personal exposure level and environmental ethylene oxide gas concentration in
      sterilization facilities of hospitals in Japan.
AB  - Personal and environmental (stationary) ethylene oxide (EO) gas concentrations in
      gas sterilization facilities were measured at six workplaces in five hospitals.
      An ethylene oxide gas monitor (3M #3551) was used for both personal and
      stationary samplings. A gas detector tube was also used for instantaneous
      sampling. In most workplaces, the personal exposure levels of EO were below the
      detection limit of the gas monitor. Most of the time-weighted average (TWA)
      concentrations by the stationary sampling were below the threshold limit value of
      EO (TLV-TWA = 1 ppm), but in one workplace, more than 4 ppm of EO were detected
      in front of the sterilizer in a clean room during a 24-hour measurement, although
      all the personal exposure levels were below the detection limit. Method of
      aeration after the sterilization was very important for reducing the EO exposure.
      The EO gas concentrations in two workplaces where sufficient aeration was carried
      out were below the detection limit in all the stationary samples. In one
      workplace where insufficient aeration was performed, EO was detected from 16 of
      17 stationary samples, and more than 90-200 ppm of EO was determined by the gas
      detector tube near the worker's face at the moment when the door of the
      sterilizer was opened and the sterilized materials were removed.

PMID- 12216594
TI  - An evaluation of ventilation system flow rates and levels of carbon dioxide,
      ambient temperature, and relative humidity in restaurants.
AB  - Studies of the indoor air quality of restaurants have rarely focused on
      ventilation system performance in relation to air pollutants and climatic
      factors. This study was conducted in eight restaurants to examine this issue by
      determining the ventilation flow rates and the levels of carbon dioxide (CO2),
      ambient temperature, and relative humidity during at least one complete shift of
      serving a meal. The mean values of number of dining patrons, ventilation flow
      rates, and the levels of CO2, ambient temperature, and relative humidity were not
      significantly different in the nonsmoking dining rooms and the smoking dining
      rooms. The mean ventilation flow rates in individual restaurants ranged from 42
      113 cubic feet per minute per person (cfm/person), overall exceeding the
      recommended lower limit of 30 cfm/person. The mean levels of CO2 in two
      restaurants (646 and 819 ppm) were below, and in the other six restaurants
      (ranging 1,012-1,820 ppm) were above the recommended upper limit of 1000 ppm. The
      levels of CO2 in each restaurant significantly correlated with the number of
      dining patrons and in four restaurants accumulated gradually over time. In the
      nonsmoking dining rooms, the levels of CO2 increased significantly as the
      ventilation How rates decreased. The mean ambient temperature in restaurants
      (ranging from 22 degrees C - 24 degrees C) were within the recommended range of
      20 degrees C - 26 degrees C. The mean relative humidity in six restaurants
      (ranging from 46%-59%) were within the recommended upper limit of 60 percent, and
      in two restaurants (62% and 71%) were slightly higher than this recommended
      limit. It was concluded that although the mean ventilation flow rates in all
      restaurants exceeded the recommended value, the design of the ventilation system
      or the distribution of air flow rate in some sections of restaurants were not
      appropriate to keep the levels of CO2 and relative humidity at some measurement
      locations below the recommended limits.

PMID- 12216595
TI  - A survey of acupuncture treatments in general practice.
AB  - This paper represents a retrospective survey of the effectiveness of acupuncture
      in an urban General Practice setting. Patients were treated within normal
      surgeries and records kept of treatments and outcomes. The paper reveals that
      when acupuncture is offered by a General Practitioner in the course of his normal
      working day, a significant number of patients can benefit without an excessive
      rise in workload.

PMID- 12216596
TI  - Acupuncture for back pain in a patient with Forestier's disease (diffuse
      idiopathic skeletal hyperostosis/DISH).
AB  - Acupuncture was used to treat a 54-year-old man with low back pain and
      Forestier's disease. His symptoms were markedly improved with acupuncture where
      other treatments in the form of analgesics, non-steroidal anti-inflammatories,
      physiotherapy and hydrotherapy had proved ineffective. There would appear to be
      no cases reported in the literature where medical acupuncture has been used to
      treat back pain in a patient with this condition.

PMID- 12216597
TI  - Infected compartment syndrome after acupuncture.
AB  - We present a case of septicaemia and compartment syndrome of the leg in a
      diabetic patient, following acupuncture to his calf. An emergency decompression
      fasciotomy was performed on the patient and gram-positive cocci were grown from
      the posterior compartment wound swab cultures and group A streptococcus from his
      blood cultures. He remained in the Intensive Therapy Unit postoperatively,
      requiring inotropic support and intravenous antibiotics for his septicaemia. We
      would like to remind acupuncturists, to consider the possibility of heightened
      risks in immunocompromised patients.

PMID- 12216598
TI  - Galactorrhoea following acupuncture.
AB  - A 41-year-old woman with breast cancer was referred to the pain management clinic
      for a course of acupuncture for intense pain following a subcutaneous mastectomy
      and a latissimus dorsi flap reconstruction. She was treated with a standard
      course of acupuncture for breast pain, using paravertebral segmental points,
      trigger points, plus contralateral L14 on the non-lymphoedematous arm. She
      experienced an episode of galactorrhoea six days following the first treatment
      and during the second treatment. She had not previously lactated for four years.
      CT and MRI of the brain revealed no focal abnormality. Acupuncture has been used
      in to promote lactation in the Traditional Chinese literature using the
      'Tianzong' acupoint SI11. This acupoint coincided with a trigger point over
      infraspinatus that was included in the neurophysiologically based acupuncture
      treatment. Quantitative analysis has shown an increase in the production of
      prolactin and oxytocin following acupuncture. These hormones are involved in the
      synthesis and release of milk from mammary glands respectively. This is the first
      report of galactorrhoea, in the contralateral normal breast, following
      acupuncture in a patient with breast cancer.

PMID- 12216599
TI  - The acupuncture murders.

PMID- 12216600
TI  - CAM launched in a Swedish geriatric unit.

PMID- 12216601
TI  - The origins of acupuncture.

PMID- 12216602
TI  - Effects of electroacupuncture on intraoperative and postoperative analgesic
      requirement.
AB  - Acupuncture has been shown to be effective in experimental and clinical acute
      pain settings. This study aims to evaluate the effect of preoperative
      electroacupuncture (EA) on intraoperative and postoperative analgesic (alfentanil
      and morphine) requirement in patients scheduled for gynaecologic lower abdominal
      surgery. Ninety patients were randomly assigned to one of three groups: Group I
      (control group)--received placebo EA for 45 minutes before induction of general
      anaesthesia (GA); Group II--preoperative EA instituted 45 minutes before
      induction of GA; Group III--45 minutes of postoperative EA. The Bispectral Index
      monitor was used intraoperatively to monitor the hypnotic effect of anaesthetic
      drugs, and alfentanil was titrated to maintain the blood pressure and pulse rate
      within +/- 15% of basal values. Postoperative pain was managed by intravenous
      morphine via a patient-controlled analgesia (PCA) device. Patients in Group II
      (0.44 +/- .15microg/kg/min) received less alfentanil than those in Group III
      (0.58 +/- .22 microg/kg/min) (p = p.024), but not significantly less than those
      in Group I 10.51 +/- 0.21 microg/kg/min) (p = 0.472). Postoperative morphine
      consumption was numerically lower in Group II compared with the other groups;
      however, the difference was statistically significant only during the period of 6
      12 hours between Group II [0.03 (0.05) mg/kg] and Group I [0.10 (0.11) mg/kg] (p
      = 0.015), and Group II and Group III [0.08 (0.10) mg/kg] (p = 0.010). The 24-hour
      cumulative morphine consumption for Group II (0.52 +/- .19mg/kg) was less than
      that for either Group I I0.68 +/- 38mg/kg) or Group III (0.58 +/- .27mg/kg), but
      the difference did not reach significance. In conclusion, preoperative EA leads
      to a reduced intraoperative alfentanil consumption, though this effect may not be
      specific, and has a morphine sparing effect during the early postoperative
      period.

PMID- 12216603
TI  - No effect of chinese acupuncture on isocapnic hyperventilation with cold air in
      asthmatics, measured with impulse oscillometry.
AB  - The cost to society and the individual of treating asthma has been increasing in
      developed countries. This has given rise to studies of the efficacy of
      complementary treatments. The aim of this study was to evaluate the efficacy of
      traditional Chinese Acupuncture in patients with mild asthma. The method used for
      evaluation of efficacy was total airway resistance at 5Hz (R5) as measured by
      impulse oscillometry (IOS)--a forced oscillation technique, at baseline and after
      a bronchial challenge with voluntary isocapnic hyperventilation of cold air
      (IHCA). The study was a parallel group randomised placebo controlled trial with
      evaluator blinding. Twenty-seven asthmatics were recruited and 24 completed the
      study, 10 of them received acupuncture and 14 received a placebo treatment (mock
      TENS). Treatment continued for 15 weeks, and efficacy was tested two weeks
      following the last treatment. Randomisation resulted in female over
      representation in the acupuncture group, but lung-function and bronchial
      responsiveness to IHCA were comparable in the two populations before the start of
      treatment (p>0.05 vs. p > 0.05). There were no statistically significant effects
      of the treatment before (p > 0.05) or after IHCA (p > 0.05) in either of the
      groups. The statistical power of the study to show a clinically relevant
      difference in bronchial responsiveness to IHCA after treatment was near 80%. We
      conclude that there were no significant effects of traditional Chinese
      Acupuncture on airway status in our patients with asthma.

PMID- 12216604
TI  - An uncontrolled pilot study of HT7 for 'stress'.
AB  - Bilateral acupuncture needling at HT7 was an effective method for reducing the
      rating of 'psychological stress' in 16 out of of a group of 17 volunteers (94%),
      recruited from staff in a hospice. Ratings were made using the Edinburgh
      Postnatal Depression Scale (EPDS), which was felt to be the most useful scale of
      those considered, despite not being validated in this population. Four brief
      acupuncture sessions were performed at weekly intervals. The greatest fall in the
      EPDS scores was observed within the first two treatments. At the end of the
      study, there was an average reduction of 44% in the EPDS scores. Further research
      is needed, including a suitable control group, to determine whether the effect
      observed in this study was a specific effect of needling at HT7.

PMID- 12216605
TI  - Superficial versus deep dry needling.
AB  - Ninety percent of my patients with myofascial trigger point (MTrP) pain have this
      alone and are treated with superficial dry needling. Approximately 10% have
      concomitant MTrP pain and nerve root compression pain. These are treated with
      deep dry needling. SUPERFICIAL DRY NEEDLING (SDN): The activated and sensitised
      nociceptors of a MTrP cause it to be so exquisitely tender that firm pressure
      applied to it gives rise to a flexion withdrawal reflex (jump sign) and in some
      cases the utterance of an expletive (shout sign). The optimum strength of SDN at
      a MTrP site is the minimum necessary to abolish these two reactions. With respect
      to this patients are divided into strong, average and weak responders. The
      responsiveness of each individual is determined by trial and error. It is my
      practice to insert a needle (0.3mm x 30mm) into the tissues immediately overlying
      the MTrP to a depth of 5-10 mm and to leave it in situ long enough for the two
      reactions to be abolished. For an average reactor this is about 30secs. For a
      weak reactor it is several minutes. And for a strong reactor the insertion of the
      needle and its immediate withdrawal is all that is required. Following treatment
      muscle stretching exercises should be carried out, and any steps taken to
      eliminate factors that might lead to the reactivation of the MTrPs. DEEP DRY
      NEEDLING (DDN): This in my practice is only used either when primary MTrP
      activity causes shortening of muscle sufficient enough to bring about compression
      of nerve roots. Or when there is nerve compression pain usually from spondylosis
      or disc prolapse and the secondary development of MTrP activity. Unlike SDN, DDN
      is a painful procedure and one which gives rise to much post-treatment soreness.

PMID- 12216606
TI  - Acupuncture mechanisms for clinically relevant long-term effects--reconsideration
      and a hypothesis.
AB  - From the author's direct involvement in clinical research, the conclusion has
      been drawn that clinically relevant long-term pain relieving effects of
      acupuncture (>6 months) can be seen in a proportion of patients with nociceptive
      pain. The mechanisms behind such effects are considered in this paper. From the
      existing experimental data some important conclusions can be drawn: 1. Much of
      the animal research only represents short-term hypoalgesia probably induced by
      the mechanisms behind stress-induced analgesia (SIA) and the activation of
      diffuse noxious inhibitory control (DNIC). 2. Almost all experimental acupuncture
      research has been performed with electro-acupuncture (EA) even though therapeutic
      acupuncture is mostly gentle manual acupuncture (MA). 3. Most of the experimental
      human acupuncture pain threshold (PT) research shows only fast and very short
      term hypoalgesia, and, importantly, PT elevation in humans does not predict the
      clinical outcome. 4. The effects of acupuncture may be divided into two main
      components--acupuncture analgesia and therapeutic acupuncture. A hypothesis on
      the mechanisms of therapeutic acupuncture will include: 1. Peripheral events that
      might improve tissue healing and give rise to local pain relief through axon
      reflexes, the release of neuropeptides with trophic effects, dichotomising nerve
      fibres and local endorphins. 2. Spinal mechanisms, for example, gate-control,
      long-term depression, propriospinal inhibition and the balance between long-term
      depression and long-term potentiation. 3. Supraspinal mechanisms through the
      descending pain inhibitory system, DNIC, the sympathetic nervous system and the
      HPA-axis. Is oxytocin also involved in the long-term effects? 4. Cortical,
      psychological, "placebo" mechanisms from counselling, reassurance and anxiety
      reduction.

PMID- 12216607
TI  - Who eats what? Classifying microbial populations based on diurnal profiles of
      rRNA levels.
AB  - Identifying the relationships between various bacterial populations and the
      substrates they consume is central to the understanding of population dynamics
      and to the development of process control in activated sludge. However, linking a
      heterotrophic population to its activity in situ is difficult because ribosomal
      RNA (rRNA) techniques, while allowing the rapid identification of populations,
      provide little information about their heterotrophic activity. Activated sludge
      models describe biodegradation kinetics by classifying substrates into two types:
      readily and slowly degradable substrates. Assuming that bacterial populations
      specialize in degrading one type of substrate, their growth rate should be
      affected differently if the COD loading rate varies diurnally as for a municipal
      activated sludge system. Modeling results suggested that the growth rates of
      populations consuming readily degradable substrates vary according to variations
      in COD loading rate. On the other hand, the growth rates of populations consuming
      slowly degradable substrates do not change despite the variation in COD loading
      rate. Since the cellular rRNA level is positively correlated with the growth
      rate, we hypothesized that the rRNA levels of some populations in municipal
      activated sludge should increase throughout the day, while they should stay
      constant for other populations. This hypothesis was verified by monitoring the
      rRNA level of Acinetobacter (a model population consuming readily degradable
      substrates) and Gordonia (a model population consuming slowly degradable
      substrates) in the mixed liquor of a full-scale municipal activated sludge
      reactor for three weeks.

PMID- 12216608
TI  - The "Nostocoida limicola" story: resolving the phylogeny of this morphotype
      responsible for bulking in activated sludge.
AB  - On the basis of 16S rRNA sequence analyses of several isolates of "Nostocoida
      limicola" from activated sludge plants in Australia and other countries, it is
      clear that "N. limicola" I, II and III are not three morphological variants of a
      single bacterium but at least three phylogenetically different bacteria. Data
      show that "N. limicola" I are members of at least two genera in the low mol% G+C
      gram-positive bacteria, while some isolates of "N. limicola" II belong to the
      high mol% G+C gram positive bacteria, and "N. limicola" III is a member of the
      Planctomycetales. Design and application of 16S rRNA targeted probes for each to
      biomass samples suggests that their phylogeny is more diverse than pure culture
      studies would suggest.

PMID- 12216609
TI  - Evaluating the role of microbial stress response mechanisms in causing biological
      treatment system upset.
AB  - It is known that microbial stress mechanisms play a significant role in short
      term microbial adaptation to environmental perturbations, and activation of these
      mechanisms enhance a cell's chance for surviving the perturbation with minimal
      damage. Although the target of these mechanisms is protective at the cellular
      level, the effect may be disruptive at the macroscopic level in engineered
      bioreactor systems. In this paper, it is proposed that these mechanisms are
      activated in response to wastewater influent perturbations and may be a
      significant cause of activated sludge treatment process upset. Selected microbial
      stress responses are reviewed and hypotheses indicating their potential role in
      treatment process upset are proposed. A research approach that was previously
      used to identify the mechanistic cause of deflocculation during perturbation by
      electrophilic chemicals is summarized, and a protocol for future experiments
      geared toward establishing source-cause-effect relationships for a range of
      wastewater upset conditions is put forth. Identifying source-cause-effect
      relationships will provide a basis for development of new monitoring technologies
      and operational strategies for systems under the influence of influent chemical
      perturbations.

PMID- 12216610
TI  - Characterization of type 1851 organism isolated from activated sludge samples.
AB  - Five orange pigmented filamentous strains of Eikelboom's type 1851 were isolated
      from bulking activated sludge, and were examined for their phylogenetic lineage,
      morphology, and physiology. The analysis of 16S rDNA sequence revealed that the
      isolates belong to Chloroflexus subdivision in green non sulfur bacteria. They
      shared most common features with type 1851, but the result of gram stain was
      negative. Furthermore, they showed polymorphic nature and gliding motility, which
      could not be seen in activated sludge samples. General physiological tests were
      conducted under aerobic conditions although they could also grow by fermentation.
      Good growth was generally seen on sugars. The extremely slow growth rate (0.48
      0.93 day(-1)) suggests the stimulation of this type exclusively in long SRT
      systems fed with sugars.

PMID- 12216611
TI  - Studies of Microthrix parvicella in situ and in laboratory culture: production
      and use of specific antibodies.
AB  - Physiological studies on M. parvicella have been conducted to determine the rate
      of growth of this organism in pure culture. The organism displayed a doubling
      time of 128 days despite its profuse abundance in a local Wastewater Treatment
      Plant (WWTW). An extensive survey has been ongoing since February 2000 into the
      extent of M. parvicella in the WWTW. A suite of monoclonal and polyclonal
      antibodies has been developed to detect and quantify M. parvicella.

PMID- 12216612
TI  - First results from a screening of filamentous organisms present in Buenos Aires's
      activated sludge plants.
AB  - Activated sludge samples from municipal and industry plants were evaluated with
      the aim to recognise the mainly filamentous bacteria found. The routine tests
      recommended were performed: Gram, Neisser, PHB-Nilo blue epifluorescence reaction
      and S. The morphologic characteristics were determined. Correlation between
      environmental conditions and abundance of dominant bacteria were made. All plants
      were completely mixed configurations with anoxic reactor for denitrification
      ahead of main aerobic reactor. Also all systems were working at low F/M values or
      high sludge age (> ten days) and in some cases with low oxygen concentration. The
      dominant species were Type 021 N, Thiothrix I, Sphaerotilus natans, Microthrix
      parvicella, Nocardia sp, Type 1701, Type 1863, Type 0041 and Type 0092.

PMID- 12216613
TI  - Presence of Rhodocyclus in a full-scale wastewater treatment plant and their
      participation in enhanced biological phosphorus removal.
AB  - The objective of this research was to assess the relevance of organisms related
      to Rhodocyclus in enhanced biological phosphorus removal in full-scale wastewater
      treatment plants. The presence of these organisms in full-scale plants was first
      confirmed by fluorescent in situ hybridization. To address which organisms were
      involved in phosphorus removal, a method was developed which selected
      polyphosphate-accumulating organisms from activated sludge samples by DAPI
      staining and flow cytometry. Sorted samples were characterized using fluorescent
      in situ hybridization. The results of these analyses confirmed the presence of
      organisms related to Rhodocyclus in full-scale wastewater treatment plants and
      supported the involvement of these organisms in enhanced biological phosphorus
      removal. However, a significant fraction of the polyphosphate-accumulating
      organisms were not related to Rhodocyclus.

PMID- 12216614
TI  - The significance of denitrifying polyphosphate accumulating organisms in
      biological nutrient removal activated sludge systems.
AB  - In this paper the advantages and disadvantages of denitrifying PAOs
      (polyphosphate accumulating organisms) in conventional BNRAS (biological nutrient
      removal activated sludge) and external nitrification BNRAS (ENBNRAS) systems are
      evaluated, with experimental data exhibiting a range of anoxic P uptake from low
      (<10%) to very high (>60%). The results indicate that the specific
      denitrification rate of the PAOs on internally stored PHB COD is about 1/5th of
      that of the "ordinary" heterotrophic organisms on SBCOD, and the PAOs contribute
      little (maximum 20%) to the denitrification in BNRAS systems even when the anoxic
      P uptake is high (60% of the total P uptake). Considering the unpredictable
      nature of anoxic P uptake and the reduction in BEPR it causes compared with
      aerobic P uptake BEPR, it is concluded that anoxic P uptake does not add a
      significant advantage to the BNR system.

PMID- 12216615
TI  - Flow cytometric sorting and RFLP analysis of phosphate accumulating bacteria in
      an enhanced biological phosphorus removal system.
AB  - Phosphate accumulating organisms (PAOs) stained with 4',6-diamidino-2-phenylindol
      dihydrochloride (DAPI) at polyphosphate probing concentration were sorted from
      enhanced biological phosphorus removal (EBPR) sludge by flow cytometric sorting.
      All the genome DNA was extracted from the sorted bacteria and the 16S rDNA genes
      were cloned. Cloned 16S rDNA was PCR-amplified and analyzed by restriction
      fragment length polymorphism (RFLP) analysis. Eighty eight clones were analyzed
      and the RFLP patterns which appeared more than twice were classified into seven
      groups. The most dominant group (Group 1) contained four clones and accounted for
      4.5% of the total clones. Four groups (from Group 2 to Group 5) contained three
      clones. Group 6 and 7 consisted of two clones. Sixty-eight clones gave unique
      RFLP patterns. By sequencing 16S rDNA in seven groups, Group 1, 2 and 5 were
      Rhodocyclus relatives (11%, 10/88). Rhodocyclus relatives were suggested to be
      one of the bacteria responsible for EBPR in this sludge. Groups 6 and 7 were
      related to b- or g-Proteobacteria. Group 4 belonged to e-Proteobacteria. Group 3
      was related to green nonsulfur bacteria. Considering the complex RFLP pattern and
      the existence of the groups not related to Rhodocyclus by sequence analysis, in
      this EBPR system, together with Rhodocyclus relatives, some other bacteria might
      also play a role as PAOs.

PMID- 12216616
TI  - Analysis of microbial community that performs enhanced biological phosphorus
      removal in activated sludge fed with acetate.
AB  - Enhanced biological phosphorus removal (EBPR) activated sludge was operated in a
      laboratory-scale sequencing batch reactor (SBR) fed with acetate as the sole
      carbon source. The microbial community of the sludge was analyzed using the
      polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE)
      method for about 2 months of start-up period. As a result, the number of major
      bands decreased during the enrichment, indicating that the microbial community
      structure was getting simpler. Since the phosphate removal activity was
      maintained at a high level, the bacteria which still remained at the end can be
      considered as the important bacteria playing key roles in the present EBPR
      sludge, maybe polyphosphate accumulating organisms (PAOs). The dominant band in
      the last sample on the DGGE gel was excised and the DNA recovered from it was
      sequenced. The sequence was closely related to one of the putative PAOs group
      which Crocetti et al. (2000) and Hesselmann et al. (1999) have proposed. This
      PAOs group is closely related to the Rhodocyclus group (b-Proteobacteria). The
      fluorescence in situ hybridization (FISH) method with the probe specific for this
      PAOs group and the DAPI staining at a phosphate-probing concentration indirectly
      showed that these Rhodocyclus related bacteria really accumulated polyphosphate.

PMID- 12216617
TI  - Polyphosphate kinase genes from activated sludge carrying out enhanced biological
      phosphorus removal.
AB  - The community structure and metabolic function of activated sludge carrying out
      enhanced biological phosphorus removal have been investigated. Laboratory-scale
      sequencing batch reactors were operated at several influent COD/P ratios to
      obtain sludges with a range of phosphorus contents. Molecular microbiological
      techniques based on small subunit ribosomal RNA were used to characterize the
      structure of these sludges. The dominant polyphosphate accumulating organism was
      a close relative of Rhodocyclus tenuis, a member of the beta subclass of the
      Proteobacteria. Fragments of genes coding for polyphosphate kinase (PPK), thought
      to be responsible for polyphosphate accumulation, were retrieved from one of the
      sludges. The relative abundance of PPK gene copies in genomic DNA extracted from
      sludges was determined to confirm that at least one of the PPK gene sequences was
      derived from the dominant polyphosphate accumulating organism.

PMID- 12216618
TI  - Population dynamics in wastewater treatment plants with enhanced biological
      phosphorus removal operated with and without nitrogen removal.
AB  - The population dynamics of activated sludge in a pilot plant with two activated
      sludge systems, both designed for enhanced biological phosphorus removal (EBPR),
      but one of them with (BNP) and the other without (BP) nitrogen removal, was
      monitored during a period of 2.5 years. The influent water to the pilot plant was
      periodically manipulated by external addition of phosphorus (P), acetate and
      glucose, respectively. The population dynamics and the in situ physiology were
      monitored by quantitative fluorescence in situ hybridization (FISH) and
      microautoradiography. Significant P removal was observed in both systems
      throughout the whole period, with significant increases of the P removal when
      substrates were dosed. The activated sludge in both systems contained large
      amounts of dense clusters of gram-negative, methylene-blue staining coccoid rods
      during the whole period. A large part of the clusters belonged to the beta
      Proteobacteria, whereas the rest of the clusters belonged either to the
      Actinobacteria or to the alpha Proteobacteria. The relative abundance of
      Rhodocyclus-related bacteria in the activated sludge varied significantly in both
      systems during the whole period (from 6 to 18% in BNP, and from 4 to 28% in BP).
      However, no statistically significant correlation of the Rhodocyclus-related nor
      any of the other investigated bacterial groups to the P content of the activated
      sludge (correlation for all groups investigated was always < 0.5) was observed. A
      significant 33Pi uptake was observed by the beta Proteobacteria (part of them
      Rhodocyclus-related, the identity of the rest unknown) and the Actinobacteria.
      However, not all of the Rhodocyclus-related bacteria showed 33Pi uptake. The P
      removal in the investigated plants is thus believed to be mediated by a mixed
      population consisting of a part of the Rhodocyclus-related bacteria, the
      Actinobacteria and other, yet unidentified bacteria.

PMID- 12216619
TI  - Role of "G-bacteria" in anaerobic substrate uptake in a SBR with no phosphorus
      removal.
AB  - Biomass from an SBR running with no enhanced biological phosphorus removal (EBPR)
      but which exhibited anaerobic assimilation of glucose and acetate, was dominated
      by "G-bacteria", cocci in tetrads and clusters. Extracted 16S rDNA was amplified
      by PCR and then analysed using Denaturing Gradient Gel Electrophoresis (DGGE).
      Major bands were extracted and their sequences determined. Clone libraries were
      also prepared, the 16S rDNA extracted, PCR performed and the resultant fragments
      run by DGGE to aid in identifying the DGGE bands and provide fuller sequences
      than available by DGGE alone. The two approaches together allowed several bands
      to be identified. Probes for FISH analyses were designed for some of these in
      attempts to see to which phylogenetic group "G-bacteria" belonged, and whether
      they represented the dominant bands detected by DGGE. Then
      FISH/Microautoradiography (MAR) was used in attempts to see which bacteria there
      were assimilating substrates anaerobically. Results indicated that the "G
      bacteria" were phylogenetically diverse, but mainly alpha-proteobacteria and
      members of the high G+C% gram-positive bacteria. Not all of these could
      assimilate glucose and/or acetate anaerobically, and Amaricoccus, the original "G
      bacteria" of Cech and Hartman, was not detected.

PMID- 12216620
TI  - Phylogenetic and physiological diversity of tetrad-forming organisms in
      deteriorated biological phosphorus removal systems.
AB  - Polyhydroxyalkanoate (PHA)- and polyphosphate-accumulating traits of different
      taxonomic tetrad-forming organisms (TFOs) in two anaerobic-aerobic sequential
      batch reactors (SBRs) were characterized by the simultaneous use of fluorescence
      in-situ hybridization, PHB stain and DAPI stain. The two SBRs with glucose as the
      main carbon source were operated under different P:total organic carbon feeding
      ratios for more than 300 days, but both exhibited no enhanced biological
      phosphorus removal (EBPR) activity. Microscopic observations on sludge samples
      taken at various times from those two SBRs revealed that TFOs consistently
      accounted for more than 50% of total cells, and were mostly affiliated with the
      beta- and gamma-subclasses of Proteobacteria and the high G+C phylum of gram
      positive bacteria (HGC). Those TFOs from the beta-Proteobcateria exhibited PHB
      stain positive and DAPI stain negative, indicating that they could utilize
      compounds other than polyphosphate (i.e. glycogen) as reducing power for PHA
      synthesis from glucose. In contrast, two types of TFOs within the HGC group
      showed negative PHB stain and positive DAPI stain, indicating their capacity to
      accumulate polyphosphate without the synthesis and degradation of PHA. This
      metabolic trait was different from the widely accepted biochemical model of EBPR
      and non-EBPR metabolisms. Other TFOs within the HGC group and gamma
      Proteobacteria showed negative responses to both PHA and DAPI stains, and their
      function in the deteriorated EBPR system need to be further clarified. Overall
      findings suggested that the phylogenic and physiological heterogeneity of TFOs in
      anaerobic-aerobic activated sludge systems were diverse and greatly exceeded the
      current understanding.

PMID- 12216621
TI  - Implementation of glycogen accumulating bacteria in treating nutrient-deficient
      wastewater.
AB  - Activated sludge treatment of nutrient-deficient wastes may lead to severe slime
      formation and consequent biomass separation difficulties. The purpose of this
      paper has been to show that bioreactor arrangement essentially influences the
      manner of biological excess carbon removal. In a comparative lab-scale experiment
      two differently arranged activated sludge systems were operated simultaneously:
      an aerated CSTR with an aerobic selector and an aerated CSTR with an anaerobic
      selector. The seed derived from an anaerobic/aerobic activated sludge plant of a
      winery. The model wastewater contained wine, sugar and acetic acid as organic
      carbon sources and lacked nutrients regarding both N and P, similarly to the
      influent of the full-scale plant. During the 52 days of the experiment the SVI
      values of the fully aerated system increased up to 600-800 cm3 g(-1) whereas
      those of the anaerobic/aerobic system remained below 250 cm3 g(-1) The SVI values
      showed a strict correlation with the amount of extracellular polysaccharides. In
      the anaerobic/aerobic experimental system, the high (40% of MLSS) intracellular
      polysaccharide content of the seed could be maintained. Besides the analytical
      data, also the microscopic observations of the biomass structure referred to the
      presence of glycogen accumulating organisms in both the lab- and full-scale
      anaerobic/aerobic systems.

PMID- 12216622
TI  - Microbial population dynamics in laboratory-scale activated sludge reactors.
AB  - As a first step in understanding nonlinear dynamics in activated sludge systems,
      two laboratory-scale sequencing batch reactors were operated under identical
      conditions and changes in their microbial communities were followed through
      microscopic examination, macroscopic observation, and denaturing gradient gel
      electrophoresis (DGGE) of PCR-amplified 16S rRNA gene segments from the
      prokaryotic community. Two experiments were performed. The first used activated
      sludge from a local wastewater treatment plant to start the replicate reactors.
      The second used the biomass from the first experiment as a source by intermixing
      the two and equally redistributing the biomass into the two replicate reactors.
      For both experiments, the two reactors behaved fairly similarly and had similar
      microbial communities for a period of 60 days following start-up. Beyond that,
      the microbial communities in the two reactors in the first experiment diverged in
      composition, while those in the second experiment remained fairly similar. This
      suggests that the degree of change occurring in replicate reactors depends upon
      the severity of perturbation to which they are exposed. The DGGE data showed that
      the bacterial communities in both experiments were highly dynamic, even though
      the system performance of the replicate reactors were very similar, suggesting
      that dynamics within the prokaryotic community is not necessarily reflected in
      system performance. Moreover, a significant finding from this study is that
      replicate activated sludge systems are not identical, although they can be very
      similar if started appropriately.

PMID- 12216623
TI  - Competition between polyphosphate- and glycogen-accumulating organisms in
      biological phosphorus removal systems--effect of temperature.
AB  - This study demonstrated that temperature is an important factor in determining
      the outcome of competition between polyphosphate-accumulating organisms (PAOs)
      and glycogen-accumulating non-poly-P organisms (GAOs) and the resultant stability
      of enhanced biological phosphorus removal (EBPR) systems. At 20 degrees C and a
      10-day sludge age, PAOs were dominant in the anaerobic/aerobic (A/O) SBR,
      however, at 30 degrees C and a 10-day sludge age, GAOs were dominant in the A/O
      SBR. For kinetic batch studies, the anaerobic specific acetate uptake rate of GAO
      dominated sludge (1.34 x 10(-3) mg C/mg VSS x minute) was higher than the rate of
      PAO-dominated sludge (0.89 x 10(-3) mg C/mg VSS x minute) at 30 degrees C,
      leading to the eventual failure of EBPR processes at high temperatures.

PMID- 12216624
TI  - Density separation and molecular methods to characterize enhanced biological
      phosphorus removal system populations.
AB  - A novel approach to the identification of microorganisms that accumulate high
      density microbial storage products based on density separation, denaturing
      gradient gel electrophoresis (DGGE), and DNA sequencing was developed and applied
      to bench and pilot scale enhanced biological phosphorus removal (EBPR) systems.
      Polyphosphate (PP), glycogen, and polyhydroxyalkanoates (PHAs), are all of higher
      density than a typical bacterial cell. PP-accumulating organisms (PAOs), the
      organisms responsible for EBPR, accumulate all three of these storage products.
      Density separation in a homogenous solution of Percoll produced a high-density
      biomass fraction with a relatively high concentration of PAOs, as determined by
      Neisser staining. DNA was extracted from these fractions, amplified, and
      separated by DGGE. DGGE profiles demonstrated some bacterial strains were present
      at a greater concentration in the high density fractions than in low density
      fractions. These strains were considered PAO candidates. 5 of 12 PAO candidates
      from high density fractions were gamma Proteobacteria and only 1 was a beta
      Proteobacterium. 2 PAO candidates were most similar to recently identified gamma
      Proteobacteria sequences obtained by DGGE analysis of a deteriorated benchtop
      EBPR system.

PMID- 12216625
TI  - An integrated approach to analyse biofilms of a full scale wastewater treatment
      plant.
AB  - A rotating biological contactor (RBC) system operating in a full-scale wastewater
      treatment plant has been described by several approaches accounting for
      performance, composition and structure of biofilms in three stages through
      biological wastewater treatment (RBC1, RBC 2, RBC 3). RBC biofilms were effective
      in removing the BOD loading from 13 g BOD5 d(-1) m(-2) in RBC 1 to 6 g BOD5 d(-1)
      m(-2) in RBC 3. Analysis of biofilm composition showed: i) the volatile solids
      were similar in the three RBCs (0.6 g m(-2) VS per g m(-2) of TS); ii) the
      protozoan and metazoan biocenosis was mainly made up of ciliated protozoa, which
      were most abundant in RBC 2 (1.84 x 10(6) ciliates g(-1) VS). Relationship
      between ciliate species and physical-chemical profile of the system by cluster
      analysis indicated that the species Acineria uncinata, Amphileptus punctatus,
      Cinetochilum margaritaceum and Holosticha mancoidea were associated with the best
      RBC performance; iii) the exopolymeric matrix of the three RBC biofilms was
      mainly constituted by proteins, although humic substances, polysaccharides,
      uronic acids and DNA were also found. Analysis of biofilm structure by confocal
      microscopy indicated changes in biofilm organisation with depth. Results have
      been brought together and a graphic representation of the composition and
      architecture of RBC biofilms is presented.

PMID- 12216626
TI  - In situ identification of azo dye inhibition effects on nitrifying biofilms using
      microelectrodes.
AB  - In this study, the inhibitory effects of acid orange 7 (AO7), a common azo dye,
      on nitrification in biofilms were investigated in situ using microelectrodes.
      Biofilms were obtained from laboratory rotating drum biofilm reactor after the
      nitrification process reached a pseudo-steady state. Dissolved oxygen, pH, NH4+,
      NO3-, and redox potential microelectrodes, with tip diameters ranging from 3-15
      microm, were used to monitor the spatial distribution and change of microbial
      activities within nitrifying biofilms. It was found that at lower concentration
      (1 mg/L), AO7 had only a slight impact on the NH4+-N concentration profiles. The
      ammonium consumption rate decreased as higher AO7 concentrations (15 mg/L and 25
      mg/L) were exposed to the biofilms. A similar trend was observed for the NO3(-)-N
      microprofiles. The nitrate production rate decreased as the AO7 concentration in
      the bulk solution increased. The dissolved oxygen and pH microprofiles also
      showed oxygen and alkalinity utilization, but at lower rates throughout the
      biofilms when the nitrification process was inhibited. No significant redox
      potential differences were observed in the biofilms after AO7 was applied.

PMID- 12216627
TI  - Production of gaseous nitrogen compounds in a novel process for ammonium removal.
AB  - The production of gaseous nitrogen compounds, particularly the greenhouse gas
      nitrous oxide, was investigated in a novel process for ammonium removal from
      wastewater. The process is based on the adsorption of ammonium on zeolite
      followed by bioregeneration. The zeolite serves the dual purpose of an ion
      exchanger and a physical carrier for nitrifying bacteria which bio-regenerate the
      ammonium saturated mineral. An analysis of the nitrifying population composition
      in the reactor fed with simulated secondary effluent (NH4+ = 50 mg/l) revealed
      that about half of the bacteria in the biofilm were common ammonium oxidizers
      Nitrosococcus mobilis and Nitrosomonas, while the other half were nitrite
      oxidizers. The amount of nitrogen losses, under different conditions, and the
      identification of the emitted gases (N2 or N2O) were investigated in two sets of
      experiments: (I) batch experiments using biomass originating from the ion
      exchange reactor with and without the addition of nitrite, and (II) continuous
      experiments using the ion exchange reactor with zeolite as the biomass carrier.
      In the batch experiments, nitrite and oxygen concentrations were determined as
      the major parameters responsible for the formation of gaseous nitrogen gas during
      ammonia oxidation by autotrophic bacteria. Continuous experiments showed that the
      major parameter significantly affecting nitrogen losses was the amount of
      ammonium adsorbed by the zeolite during the ion exchange phase. The amount of
      ammonium adsorbed determines the ammonium concentration during the initial period
      of bioregeneration, which in turn directly influences oxygen demand and the
      resulting concentrations of oxygen and nitrite. It was concluded that the
      formation of nitrogen gas compounds in the ion exchange/bioregeneration process
      can be eliminated by adjusting the operational regime to have a shorter
      adsorption phase resulting in smaller amounts of ammonium adsorbed per cycle.

PMID- 12216629
TI  - Structure and function of nitrifying biofilms as determined by molecular
      techniques and the use of microelectrodes.
AB  - The phylogenetic diversity of a nitrifying bacterial community of two types of
      nitrifying biofilms, a domestic wastewater biofilm and an autotrophic nitrifying
      biofilm grown on rotating disk reactors (RDR), was characterized by 16S ribosomal
      DNA (rDNA)-cloning analysis. Thereafter, successional development of nitrifying
      the bacterial community within both biofilms was visualized in situ by
      fluorescent in situ hybridization (FISH) wih a set of fluorescently labeled 16S
      rRNA-targeted DNA probes. In situ hybridization revealed that Nitrosomonas ureae
      was the numerically dominant species of the ammonia-oxidizing population in the
      domestic wastewater biofilm and that a population shift from N. urea to N.
      europaea and N. eutropha occurred when the culture medium was switched to the
      synthetic media from the domestic wastewater. After reaching the steady-state
      condition, microprofiles of NH4+, NO2-, NO3-, and O2 in the biofilms were
      measured by use of microsensors, and the spatial distributions of in situ
      nitrifying activities were determined. The relationship between the spatial
      organization of nitrifying bacterial populations and the in situ activity of
      these populations within the biofilms was discussed. Microelectrode measurements
      revealed that the active ammonia-oxidizing zone was vertically separated from the
      active nitrite-oxidizing zone. This vertical separation became more evident with
      increase of the substrate C/N ratio, leading to deterioration of nitrification
      efficiency. The combined use of these techniques made it possible to relate in
      situ nitrifying activity directly to the occurrence of nitrifying bacterial
      populations.

PMID- 12216628
TI  - Deammonification in biofilm systems: population structure and function.
AB  - For the development of alternative concepts for the cost effective treatment of
      wastewaters with high ammonium content and low C/N-ratio, autotrophic consortia
      of micro-organisms with the ability to convert ammonium directly into N2 are of
      particular interest. Several full-scale industrial biofilm plants eliminating
      nitrogen without carbon source for years in a stable process, are suspected for
      some time to harbor active anaerobic ammonium oxidizers in deeper, oxygen-limited
      biofilm layers. In order to identify the processes of the single-stage nitrogen
      elimination (deammonification) in biofilm systems and to allocate them to the
      responsible micro-organisms, a deammonifying moving-bed pilot plant was
      investigated in detail. 15N-labelled tracer compounds were used as well as 16S
      rDNA libraries and in situ identification of dominant organisms. The usage of
      rRNA-targeted oligonucleotide probes (FISH) was particularly emphasized on the
      ammonium oxidizers of the beta-subclass of Proteobacteria and on the members of
      the order Planctomycetales. The combined application of these methods led to a
      deeper insight into the population structure and function of a deammonifying
      biofilm.

PMID- 12216630
TI  - Ciliated protozoa and organic load at low temperatures in an aerated biofilter.
AB  - Ciliated protozoa have been widely used as water quality indicators because their
      main morphological characteristics are relatively simple to identify
      microscopically. The species and individual numbers in wastewater treatment
      systems are a consequence of the operational and environmental conditions of the
      process. The main objective of this research was to relate the effluent quality
      of a pilot aerated biofilter with the presence and relative abundance of ciliated
      protozoa when operated under different organic loading rates. The experimental
      work was done in a pilot aerated biofilter using 12 mm volcanic porous stones as
      filtering media and it was fed with municipal wastewater adjusting the
      experiments to 3 organic loading rates (3, 7, and 9 gCOD/m2 x d). Temperature in
      the filter varied from 11 to 14 degrees C during the experimental work. COD and
      BOD removal rates do not change significantly with the different organic loads.
      Nitrification improves inversely to the organic load and it does not show
      dependence on the slight temperature changes observed. Eighteen species were
      identified as typical residents in wastewater systems. Free swimming species
      prefer higher organic loads. Crawling and attached species did not show
      significant changes with the organic load. According to the saprobity index of
      Pantle and Buck, the system, independently of the organic load, presented typical
      alpha-mesosaprobe level.

PMID- 12216631
TI  - Simulation of biofilm growth, substrate conversion and mass transfer under
      different hydrodynamic conditions.
AB  - The hydrodynamic conditions and the substrate load in biofilm systems are two
      main parameters which influence the biofilm growth in particular the structure,
      density and thickness. In a long term study on heterotrophic biofilms in biofilm
      tube reactors the investigation has focussed on mass transfer at the bulk/biofilm
      interface, the biofilm density and the substrate conversion rates. To study the
      mass transfer phenomena at the bulk/biofilm interface oxygen profiles have been
      measured directly in tube reactors with microelectrodes. Microelectrode studies,
      substrate conversion rates and biofilm densities were used to formulate model
      equations for the simulation of biofilm growth under different hydrodynamic and
      substrate conditions. It can be shown that the mass transfer at any time is
      strongly coupled with the growth conditions during the biofilm cultivation. On
      the one side the calculated Sherwood numbers were coupled to the present
      hydraulic conditions, on the other side in addition the growth conditions such as
      growth rate and Reynolds number during biofilm cultivation were considered.

PMID- 12216632
TI  - Biofilm development in down flow anaerobic fluidised bed reactors under transient
      conditions.
AB  - Biofilm development onto polypropylene particles (<4 mm) was studied in a
      laboratory-scale down flow anaerobic fluidised bed reactor. The reactor was fed
      with a synthetic solution containing sucrose and nutrients, and operated at 35
      degrees C during 65 days at 44% bed expansion rate and 36 h HRT. Scanning
      electron microscopy (SEM) monitored the biofilm development. Initial adhesion
      occurred within the first 6 hours and after day 44 biofilm structure was
      complete. The presence of attached cells morphologically similar to Methanotrix
      bacilli and Methanosarcina sp. was observed by Scanning Electron Microscopy
      (SEM). The biofilm and the carrier surface roughness were measured by atomic
      force microscopy (AFM) and yielded 9.1 and 75 nm respectively. Results also
      showed good correlation between the SEM characterisation and the conventional
      anaerobic reactor parameters.

PMID- 12216633
TI  - Population dynamics in an aerobic submerged fixed bed reactor (ASFBR) process.
AB  - In this study, an aerobic submerged fixed bed reactor's (ASFBR) population
      dynamics has been studied in order to know its behavior in different conditions
      of organic load and oxygen concentration. The reactor was fed with synthetic
      wastewater. Tested variables and applied values were: 1) Variations in organic
      load (OL): 16-65 g COD/m2/d. 2) Variations in influent's COD concentration: 40
      400 g COD/m3. 3) Variations in specific air flow (SAF): 15-127 m3air/kgCOD.
      Biofilm samples were taken at the top of the reactor. This study showed important
      variations in the composition and abundance of the microfauna depending on the
      experimental conditions. Variations in influent concentration had no significant
      effect on the abundance of the studied groups. However, differences depending on
      organic load and aeration conditions were observed. Organic load influenced every
      group studied but with different results. Sessile cilliates, metazoa and
      flagellates were abundant in low load, while crawling ones were in high load.
      Aeration intensity influenced most of the groups except Peranema and Vorticella
      spp. Despite obtaining good yields, not many protozoa, typical of biofilms under
      conventional processes, were found. Thus, a great variety of microorganisms, such
      as many classes of sessile and crawling cilliates, were not found. Important
      nitrifying activity was obtained at 20 cm depth in a bed. From this point, the
      heterotrophic and nitrifying populations exist but are inactive.

PMID- 12216634
TI  - The characteristics of the biofilm fixed inside porous medium by sequencing batch
      reactor.
AB  - The fixed biomass inside porous medium has two layers where biomass yield
      constants are different from each other when it is cultivated in the chemostat
      reactor. The biomass fixed inside porous medium is tested to see whether the
      operation type affected the structure of it. Two kinds of operation method of the
      reactor were used for the biofilm cultivation. One is the batch reactor. Another
      is the chemostat reactor. From the kinetic test, it is found that the biofilm
      fixed in the batch reactor does not have two layers that were observed in the
      biofilm from the chemostat reactor. Within the experimental conditions for type
      1, the result of kinetic tests show homogeneous biofilm characteristics. It can
      be concluded that the reactor type (batch type or chemostat type) affects the
      structure of biomass fixed inside porous medium.

PMID- 12216635
TI  - The development and use of real-time PCR for the quantification of nitrifiers in
      activated sludge.
AB  - Chemical analytical data has long been used to monitor the performance of
      activated sludge plants even though the process relies on the performance of
      microorganisms. It is now evident that a rapid and reliable quantitative method
      is required, to be able to monitor the organisms responsible for nutrient
      transformation and their activities, allowing avenues for more efficient nutrient
      removal. The development of real-time or quantitative polymerase chain reaction
      (PCR) also known as TaqMan or 5'-nuclease assay has allowed the rapid,
      quantitative analysis of DNA templates, eliminating some of the variability
      traditionally associated with other quantitative techniques. In this study
      analysis of Nitrospira spp., one of the key organisms in nitrite oxidation in
      wastewater treatment, was used to validate real-time PCR for the their
      quantification in activated sludge. A probe and primer set, targeting the 16S
      rRNA gene of Nitrospira spp. was designed according to the constraints of the
      TaqMan specifications. Samples used to evaluate the method included DNA from the
      sludge from full-scale wastewater treatment plants and laboratory scale systems.
      The reproducibility, quantitative efficiency and specificity were assessed in the
      evaluation. It was concluded that the method is sensitive and reproducible but
      has some constraints on the quantitative efficiency. A survey of full-scale
      systems for Nitrospira spp. was carried out and the results are presented here.

PMID- 12216636
TI  - Molecular analysis of ammonia-oxidizing bacterial populations in aerated-anoxic
      orbal processes.
AB  - Aerated-anoxic processes operate under the principle that small additions of
      oxygen to an anoxic reactor induce simultaneous nitrification and
      denitrification. In these systems, ammonia oxidation in the anoxic zone can
      easily account for 30-50% of the total nitrification in the reactor, even though
      the dissolve oxygen concentration is usually below detection limit. To
      investigate whether the nitrification efficiency in aerated-anoxic processes was
      due to the presence of specialized ammonia-oxidizing bacteria (AOB), an analysis
      of the AOB population in an aerated-anoxic Orbal process and a conventional
      nitrogen removal process was carried out using phylogenetic analyses based on the
      ammonia monooxygenase A (amoA) gene. Terminal restriction fragment length
      polymorphism (TRFLP) analyses revealed that Nitrosospira-like organisms were one
      of the major contributors to ammonia oxidation in a full-scale aerated-anoxic
      Orbal reactor. However, the relative populations of Nitrosospira-like and
      Nitrosomonas-like AOB were not constant and appeared to have seasonal
      variability. Cloning and sequence comparison of amoA gene fragments demonstrated
      that most of the AOB in the aerated-anoxic Orbal process belonged to the
      Nitrosospira sp. and Nitrosomonas oligotropha lineages. The abundance of
      Nitrosospira-like organisms in aerated-anoxic reactors is significant, since this
      group of AOB has not been usually associated with nitrification in wastewater
      treatment plants.

PMID- 12216637
TI  - Detection and quantification of expression of amoA by competitive reverse
      transcription-pCR.
AB  - Ammonia oxidation by chemolithoautotrophic ammonia-oxidizing bacteria is an
      important step in the biological nitrogen removal process. The first conversion
      step, the oxidation of ammonia to hydroxylamine is catalyzed by ammonia
      monooxygenase (AMO). To investigate the activity of ammonia oxidation, mRNA
      (designated as amoA) encoding a subunit of AMO was quantified by competitive
      reverse transcription (RT)-PCR. As a result, it was possible to detect and
      quantify amoA expression in cultured Nitrosomonas europaea and even complex
      microbial communities such as nitrifying bacterial aggregates by competitive RT
      PCR. It was estimated that amoA concentration in cultured N. europaea was 2.3 x
      10(8) copies x ml(-1). Additionally, it was calculated that the copy number of
      amoA in nitrifying bacterial aggregates was 1.0 x 10(12) copies x ml(-1) (5.1 x
      10(10) copies x mg(-1)-dry weight). On the other hand, amoA expression in the
      natural activated sludge in a household Gappei-Johkaso was undetectable, whereas
      16S rRNA of ammonia-oxidizing bacteria was detected by RT-PCR. Then, four days
      cultivation of this sludge in inorganic artificial wastewater resulted in
      increasing amoA expression to a quantifiable amount by competitive RT-PCR. In
      conclusion, the competitive RT-PCR was effective to investigate the expression of
      amoA as an indicator of ammonia oxidation activity by autotrophic ammonia
      oxidizing bacteria.

PMID- 12216638
TI  - Comparison of bench scale testing methods for nitrifier growth rate measurement.
AB  - The maximum specific nitrifier growth rate was determined for two wastewater
      treatment plants (WWTPs) using sequencing batch reactors (SBRs) and high F/M
      exponential growth batch tests. Higher nitrifier growth rates were obtained from
      the exponential growth batch tests. Operating SRT and aeration mode (fully
      aerobic versus anoxic/aerobic) significantly impacted the nitrifier's growth rate
      in the SBRs with lower SRT and anoxic/aerobic operation resulting in higher
      specific nitrifier growth rates.

PMID- 12216639
TI  - Control of bulking sludge caused by Type 021 N and Type 0961 in an industrial
      wastewater treatment plant with an aerobic selector.
AB  - Over a period of 6 months, pilot plant investigations were carried out with the
      purpose of bulking sludge control with different aerobic selectors. The
      wastewater was dominated by industrial dischargers, containing volatile fatty
      acids up to 450 mg/l. With complete-mix-selectors it was not possible to achieve
      a stable SVI below 150 ml/g. The bulking sludge could only be controlled with a
      sectionalized selector (HRT 5-8 minutes per section). The SVI decreased to values
      below 100 ml/g. Shock-loads and increased VFA-concentrations (by dosing NaC2H3OO)
      did not cause filamentous growth.

PMID- 12216640
TI  - Differences in nitrification potential between fully aerobic and nitrogen removal
      activated sludge systems.
AB  - Experimental observations made on two pilot plants, showed that nitrogen removal
      activated sludge systems, operating under favourable conditions, seem to develop
      increased nitrification potential compared to fully aerobic systems under similar
      conditions. This increased potential, which cannot be detected by simple
      nitrification performance evaluations, is attributed to higher autotrophic
      populations sustained--developed in similar systems employing anoxic reactors or
      phases. A reduced autotrophic decay rate under anoxic conditions as reported by
      some researchers, seems to play a significant role in such a response, most
      likely together with a more efficient use of available nitrogen for additional
      nitrifying microorganisms production, resulting from a reduced nitrogen loss to
      autotrophic biomass maintenance needs and heterotrophic biomass synthesis
      requirements.

PMID- 12216642
TI  - Experimental assessment and modelling of nitrate utilisation for primary sludge.
AB  - Electron acceptor utilisation potential of filtered primary sludge under anoxic
      conditions was experimentally investigated. Major kinetic and stoichiometric
      parameters were assessed by means of model evaluation of nitrate profile obtained
      in batch reactors. ASM1, modified for endogenous decay, and ASM3 were used for
      model simulation. Both models provided consistent interpretation of experimental
      data. ASM1 yielded mu(H) and Y(HD) values of 6.1 d(-1) and 0.64 g cell COD(g
      COD)(-1) respectively for heterotrophic anoxic growth. The corresponding storage
      mechanism associated with ASM3 could be characterised by a k(STO) of 13 g COD (g
      COD d)(-1) and a Y(STO) of 0.78 g COD(g COD)(-1). The high k(STO) value suggests
      re-evaluation of the concept of readily biodegradable substrate as defined in
      ASM3 and tested in the study.

PMID- 12216641
TI  - Evaluation of autotrophic denitrification, heterotrophic nitrification, and PAOs
      in full scale simultaneous biological nutrient removal sysyems.
AB  - Anoxic and aerobic batch reactor assays using a two-by-two factorial design were
      developed to determine the potential activity of autotrophic denitrification and
      heterotrophic nitrification in biological nutrient removal (BNR) activated sludge
      systems, especially those accomplishing simultaneous BNR (SBNR). Results from the
      application of these assays to three full scale closed loop bioreactors
      previously documented to be accomplishing SBNR demonstrated that these activities
      were minimal in comparison with the conventionally recognized activities of
      heterotrophic denitrification and autotrophic nitrification. Activity within the
      mixed liquor consistent with current theories for phosphorus accumulating
      organisms (PAOs) was also observed. Along with other observations, this suggests
      the presence of PAOs in the facilities studied.

PMID- 12216643
TI  - A comparison of autotrophic ammonia-oxidizing bacteria in full- and laboratory
      scale wastewater treatment reactors.
AB  - Lab-scale reactors are commonly used to simulate full-scale plants as they permit
      the effects of defined experimental perturbations to be evaluated. Ideally, lab-
      and full-scale reactors should possess similar microbial populations. To
      determine this we compared the diversity of the beta-proteobacterial autotrophic
      ammonia-oxidising bacteria (AOB) in a full-scale and lab-scale biological aerated
      filter (BAF) using PCR with AOB selective primers combined with denaturing
      gradient gel electrophoresis (DGGE). PCR amplified 16S rRNA gene fragments from
      the nitrification unit of the lab-and full-scale BAF were subjected to cloning
      and sequencing to determine the phylogenetic affiliation of the AOB. A high
      degree of comparability between the lab-and full-scale BAF was observed with
      respect to AOB populations. However minor differences were apparent. The
      importance of these minor constituents in the overall performance of the reactor
      is unknown. Nonetheless the lab-scale reactor in this study did appear to reflect
      the dominant AOB community within the full-scale equivalent.

PMID- 12216644
TI  - Modelling population dynamics of denitrifying phosphorus accumulating organisms
      in activated sludge.
AB  - In this paper a kinetic model for simulating population dynamics is developed.
      The aim was to simulate anoxic and aerobic phosphorus accumulating organisms
      dynamics in a lab-scale sequencing batch reactor (SBR) operating under different
      conditions. Denitrifying phosphorus accumulating organisms (DNPAOs) successfully
      competed in almost all the simulated operational conditions tested. Using this
      model, the anoxic energy disadvantage of DNPAOs was not as strong as using
      metabolic models. The model was able to predict reasonably well N, P and acetate
      profiles in the SBR with only a minor modification of the ASM2d default values of
      the parameters.

PMID- 12216645
TI  - Benchmarking nitrogen removal suspended-carrier biofilm systems using dynamic
      simulation.
AB  - We are witnessing an enormous growth in biological nitrogen removal from
      wastewater. It presents specific challenges beyond traditional COD (carbon)
      removal. A possibility for optimised process design is the use of biomass
      supporting media. In this paper, attached growth processes (AGP) are evaluated
      using dynamic simulations. The advantages of these systems that were
      qualitatively described elsewhere, are validated quantitatively based on a
      simulation benchmark for activated sludge treatment systems. This simulation
      benchmark is extended with a biofilm model that allows for fast and accurate
      simulation of the conversion of different substrates in a biofilm. The economic
      feasibility of this system is evaluated using the data generated with the
      benchmark simulations. Capital savings due to volume reduction and reduced sludge
      production are weighed out against increased aeration costs. In this evaluation,
      effluent quality is integrated as well.

PMID- 12216646
TI  - PCR-DGGE analysis of denitrifying bacteria in a metallurgic wastewater treatment
      process.
AB  - The wastewater generated from the processes of recovering precious metals from
      industrial wastes contains high concentrations of acids such as nitric acid and
      of salts. Biological nitrogen removal from this wastewater was attempted by using
      a circulating bioreactor system equipped with an anoxic packed bed or an anoxic
      fluidized bed and an aerobic three-phase fluidized bed. The system was found to
      effectively remove nitrogen from the diluted wastewater (T-N; 1,000-4,000 mg
      litre(-1)). The microbial population structure of activated sludge in an anoxic
      reactor was analyzed by denaturing gradient gel electrophoresis (DGGE) of PCR
      amplified 16S ribosomal DNA (rDNA) fragments. DGGE analysis under different
      operating conditions demonstrated the presence of some distinguishable bands in
      the separation pattern, which were most likely derived from many different
      species constituting the microbial communities. Furthermore, the population
      diversity varied in accordance with the nitrate-loading rate, water temperature
      and reactor condition. Some major DGGE bands were excised, reamplified and
      directly sequenced. It was revealed that the dominant population in the anoxic
      reactor were affiliated with the beta subclass of the class Proteobacteria.

PMID- 12216647
TI  - PHA storage from several substrates by different morphological types in an
      anoxic/aerobic SBR.
AB  - An activated sludge was cultivated on a mixture of several soluble substrates
      (acetate, ethanol, glucose, glutamic acid, peptone, Tween 80, starch, yeast
      extract) in an anoxic/aerobic SBR. Highly dynamic conditions in the SBR (feast
      famine regime) caused fast removal of most COD in the anoxic phase (in particular
      acetate, ethanol, glutamic acid and glucose were totally removed) and relevant
      contribution of storage. In spite of that, filament abundance was always high, as
      is typical of bulking sludges. Filaments which developed in the reactor were
      characterized on a morphological basis and on the basis of their ability to grow
      and to store polyhydroxyalkanoates (PHAs). Three main filaments prevailed in the
      biocenosis, whose relative abundance was varyng with time: Nostocoida limicola
      II, (two different morphological types), Haliscomenobacter hydrossis and an
      unidentified one. It was found that maximum growth rate was higher for
      flocformers than for filaments on each of the tested substrates. Epifluorescence
      showed that storage ability was more widespread among flocformers than in the
      filaments. Only one type of Nostocoida limicola II was able to store PHAs. The
      obtained data show that aerobic growth on the little residual fraction of COD
      from the anoxic phase was enough to support high abundance of filamentous
      microorganisms.

PMID- 12216649
TI  - Oxidation-reduction potential (ORP) regulation of nutrient removal in activated
      sludge wastewater treatment plants.
AB  - Redox potential (ORP) regulation of nutrient removal in aeration tanks was tested
      for one year in three activated sludge wastewater treatment plants in Cincinnati,
      OH. The experiment results show a good relationship between ORP values and
      nutrient removal. Macro-biodegradation and sorption of substrate by activated
      sludge can significantly increase wastewater ORP, indicating the improvement of
      redox status of the bulk liquor. DO higher than 1.0 mg/L is necessary for good
      biodegradation and the improvement of liquid redox status. ORP values at higher
      temperatures (Twater = 20-26 degrees C) were lower than ORP values at lower
      temperatures (Twater = 14-19 degrees C), caused by the lower oxygen saturation
      capacity in wastewater and the more rapid oxygen consumption by microorganism
      under warmer conditions. Nitrification occurred at higher ORP values (380 mV)
      than did organic substrate oxidation (250 mV). This verifies that different
      metabolic processes dominate in different ORP ranges. The pilot-scale experiment
      results demonstrate that the wastewater ORP values continued to increase
      throughout the whole 6-hour cycle when the influent COD was higher than 1,000
      mg/L. For influent with low COD (40-120 mg/L), the wastewater ORP values did not
      increase in the second 3 hours of the cycle, during which time the microbial
      biodegradation within the activated sludge floc dominated. High DO concentrations
      (6-8 mg/L) did not help improve the redox status. In fully-aerated wastewater,
      oxygen deeply penetrated into the activated sludge flocs, and microorganisms
      biodegraded the substrates within the flocs. Endogenous metabolism predominated.

PMID- 12216648
TI  - Respirometric assessment of storage yield for different substrates.
AB  - A new procedure has been defined for the respirometric assessment of bacterial
      storage yield as defined in the Activated Sludge Model No.3. The procedure was
      used to determine the storage yield, Y(STO), associated with acetate, glucose and
      domestic sewage, together with mixtures of acetate/glucose and acetate/domestic
      sewage at different initial F/M ratios. Y(STO) was calculated as 0.78 gCOD(gCOD)(
      1) for acetate, 0.87 gCOD(gCOD)(-1) for glucose and 0.96 gCOD(gCOD)(-1) for
      domestic sewage. The Y(STO) of substrate mixtures was found to reflect the
      characteristics of the dominant fraction in the mixture.

PMID- 12216650
TI  - Change in metabolism of PHA accumulation by activated sludge modifying operating
      conditions.
AB  - In the present work, sludge from a stable and efficient phosphorus removal
      process was used to evaluate the change in the metabolism when the reactor
      operation was modified from anaerobic/aerobic to aerobic dynamic substrate
      feeding. The change in operational conditions allowed the population to modify
      the metabolism of phosphorus and polyhydroxyalkanoates (PHA) accumulation. Under
      aerobic dynamic feeding, phosphorus accumulation was almost hindered while the
      amount of PHA accumulation increased significantly. After ten days of operation
      under dynamic substrate feeding, the reactor operation turned back to
      anaerobic/aerobic cycles and the metabolism of phosphorus was progressively
      recovered.

PMID- 12216651
TI  - Gas chromatographic analysis of polyhydroxybutyrate in activated sludge: a round
      robin test.
AB  - Polyhydroxyalkanoates (PHA) and poly-beta-hydroxybutyrate (PHB) in particular
      have become compounds which is routinely investigated in wastewater research. The
      PHB analysis method has only recently been applied to activated sludge samples
      where PHA contents might be relatively low. This urges the need to investigate
      the reproducibility of the gas chromatographic method for PHB analysis. This was
      evaluated in a round-robin test in 5 European laboratories with samples from lab
      scale and full-scale enhanced biological phosphorus removal systems. It was shown
      that the standard deviation of measurements in each lab and the reproducibility
      between the labs was very good. Experimental results obtained by different
      laboratories using this analysis method can be compared. Sludge samples with PHB
      contents varying between 0.3 and 22.5 mg PHB/mg sludge were analysed. The gas
      chromatographic method allows for PHV, PH2MB and PH2MV analysis as well.

PMID- 12216652
TI  - Study of filamentous bacteria by image analysis and relation with settleability.
AB  - An automated procedure for the characterisation by image analysis of the
      morphology of activated sludge has been used to monitor the biomass in a pilot
      wastewater treatment plant during two runs inoculated with a different sludge and
      operated at two different temperatures. The bulking events were easily detected
      by image analysis. Correlations were found between settleability properties
      (Sludge Volume Index and settling velocity) and the morphological parameters
      (filament total length, filament number and floc size).

PMID- 12216653
TI  - Biomass active fraction evaluated by a direct method and respirometric
      techniques.
AB  - The knowledge of the active biomass amount and its characterisation is of primary
      importance for the management and for the design of wastewater treatment plants
      on the basis of the recently developed models. OUR curves obtained in aerobic
      exponential growth tests are proposed by several authors as an indirect method to
      estimate the active fraction. The aim of this work is the application of a direct
      method to measure the viable biomass based on flow cytometry techniques and the
      comparison with the active fraction obtained from respirometric tests. To assess
      the viable fraction of a biomass expressed in terms of COD concentration it is
      necessary to estimate the biovolume of viable bacteria and to know the specific
      carbon content per cell. For the investigated activated sludge samples, the
      bacterial biomass measured by FCM was 588 mgCOD L(-1) on average in a two-months
      period. This value of active fraction corresponds to 14% of particulate COD.
      Active biomass values measured with the respirometric approach were consistent
      but generally higher than those obtained by FCM.

PMID- 12216654
TI  - On the development of a novel image analysis technique to distinguish between
      flocs and filaments in activated sludge images.
AB  - The ratio of flocs to filaments in activated sludge wastewater treatment plants
      is of extreme importance for the overall performance of the plant. In order to
      control this ratio the individual concentrations of flocs and filaments need to
      be measurable. However, no sensors which can measure these concentrations are
      currently available. In this paper it is outlined how a distinction can be made
      between flocs and filaments by means of image analysis techniques. Combination of
      this information with the total biomass concentration results in the individual
      floc and filament concentrations. The distinction of objects of interest from the
      background is a crucial step in the image analysis procedure. An automatic
      thresholding algorithm is proposed which selects two thresholds in images with
      one fraction darker than the background and the other fraction brighter than the
      background. Once the objects are separated from the background, they are
      classified as either flocs or filaments by means of the reduced radius of
      gyration.

PMID- 12216656
TI  - Bacteriophage-host interaction in the enhanced biological phosphate removing
      activated sludge system.
AB  - Bacteriophages were isolated from a laboratory scale enhanced biological
      phosphate removing (EBPR) activated sludge process, and their host range was
      examined. Bacterial isolates to host the bacteriophages were isolated from the
      EBPR activated sludge process. Bacteriophages were eluted from the EBPR activated
      sludge, enriched by incubation with the bacterial isolates, and then tested for
      plaque formation on each of the bacterial isolates. Out of 12 bacterial isolates
      isolated, 4 supported plaque formation. Four bacteriophages were obtained from
      the plaques. The host range test was conducted with the combination of the
      bacteriophage isolates and the bacterial isolates. Three of the bacteriophages
      were found to form plaques on more than one host, and one of them formed plaques
      on both gram +ve and gram -ve bacterial isolates. Two of the four bacteriophages
      failed to form plaques on their original bacterial host, indicating the existence
      of mutation on either both or one of the host and the bacteriophage. This study
      strongly suggests that bacteriophages are an active part of the activated sludge
      microbial ecosystem, having very complex interaction with their host bacteria.

PMID- 12216655
TI  - Quantification of functional groups in activated sludge by microautoradiography.
AB  - Different functional groups of bacteria in activated sludge from a Danish
      municipal wastewater treatment plant were investigated and quantified on the
      basis of their ability to take up acetate under different electron acceptor
      conditions. The number of bacteria in the different functional groups was
      quantified by microautoradiography or by fluorescence in situ hybridization
      (FISH). Uptake of radiolabeled acetate was tested under conditions where oxygen,
      nitrate, ferric iron, and sulfate served as electron acceptors and under
      methanogenic conditions. Ammonia-oxidizing bacteria and nitrite-oxidizing
      bacteria were enumerated by applying oligonucleotide probes (FISH). 80% of the
      total DAPI count hybridised with a mixture of bacterial probes. Most baceria were
      able to take up acetate with oxygen or nitrate as electron acceptors (74 and 71%
      of all DAPI-stained bacteria, respectively). The very similar numbers indicate
      that the alternating aerobic and anoxic conditions in the wastewater treatment
      plant investigated favoured the presence of facultative aerobic and denitrifying
      heterotrophic bacteria. The number of bacteria able to take up acetate under
      anaerobic conditions was around 8% of the total DAPI count. About half of these
      were able to take up acetate and store it and were thus probably phosphate
      accumulating organisms. The remaining 4% of anaerobic acetate-consuming bacteria
      were mainly iron reducers. By incubating the sludge samples with specific
      inhibitors against sulfate reduction and methanogenic activity, it was found that
      sulfate reducers and methanogenic bacteria constituted approximately 1% and less
      than 0.5% of the total DAPI count, respectively.

PMID- 12216657
TI  - Active heterotrophic and autotrophic biomass distribution between fixed and
      suspended systems in a hybrid biological reactor.
AB  - This paper presents the results obtained when modifying sludge retention time
      (SRT 8, 5, and 3.7 days during phases A, B and C respectively) for a hybrid
      biological reactor (HR) compared with a classical activated sludge process. The
      study was conducted by following active biomass evolution and distribution for
      two lab-scale pilots plants operating with the same conditions, one acting as HR
      and the other as the control reactor (CR) without support material. At the end of
      phase C, support material was split into two fractions between both reactors to
      study the effect of support to reactor volume ratio (Fr). Active biomasses in
      suspended and fixed systems were calculated using respirometric techniques.
      Evolutions of active autotrophic and heterotrophic biomasses for both reactors
      are presented during all the operational periods and it is observed that in the
      HR biomass concentrations are up to double that in the CR, mainly due to the
      presence of support material. When studying biomass distribution in HR,
      autotrophic biomass is mainly located over the support material (from 95% to 99%
      during periods A and C respectively) while only about 60% of heterotrophic
      biomass is located over the support.

PMID- 12216658
TI  - Community structure of micro- and macroflocs in pin-point sludge and the
      influence of sludge age and potassium addition on microfloc formation.
AB  - Settling problems caused by pin-point sludge constitute a serious problem in
      biological wastewater treatment, particularly in many industrial plants. Until
      now, most studies focused on the relationship between pin-point sludge formation
      and either shearing forces or the impact of toxicants. This study deals with the
      community structure in both the micro- and macrofloc fraction which was analyzed
      by fluorescent in situ hybridization (FISH) and BIOLOG substrate utilization
      patterns. It was shown that each fraction consisted of different microbial
      communities with unique metabolic profiles suggesting that pin-point sludge
      formation is not due to dispersal of intact flocs but to microcolonies growing
      separately. Alternatively, macroflocs may have an architecture leading to
      segregation of microbial communities after floc dispersal. Further it could be
      shown that the formation of microflocs was influenced by sludge age. The best
      sludge sedimentation was obtained for a sludge age of 5 and 10 days. Additional
      analysis of extracellular polymeric substances (EPS) suggested that the lower
      protein to carbohydrate ratio of 10-day-old sludge led to better flocculation
      compared to 20-day-old sludge containing similar total amounts of EPS. From a
      practical point of view, addition of potassium (0.1 g/l) effected a noticeable
      improvement of sludge settleability.

PMID- 12216659
TI  - A comparison among different methods for evaluating the biomass activity in
      activated sludge systems: preliminary results.
AB  - In order to improve activated sludge plant operation (achieving higher efficiency
      and cost savings) beside influent and effluent characteristics and working
      parameters (e.g. dissolved oxygen, total and volatile suspended solids, pH,
      recirculation flow rate, etc.), the biomass activity should be monitored, the
      bacteria being responsible for the pollutant degradation. Since conventional
      cultivation based methods are inadequate to quantify environmental microorganisms
      (due to scarce number of cultivable microorganisms and time-consuming procedures)
      several "non-conventional" techniques were applied in this study, in order to
      compare the obtainable information and their routine feasibility. Different
      measurements (VSS concentration, Oxygen Uptake Rate, microbial counts by cultural
      and biomolecular methods--MPN-PCR, ATP content, dehydrogenase activity, microbial
      cell viability and enzymatic activity) were carried out on mixed liquor samples,
      taken from a municipal activated sludge plant (440,000 p. e.). The preliminary
      results of the research are presented in this paper.

PMID- 12216660
TI  - The effect of flow pattern on kinetic characteristic of the biomass fixed inside
      porous medium.
AB  - The characteristics of the biomass fixed inside porous medium (sponge cube) have
      been investigated to see whether it can be recognized as biofilm. The acrylic
      cube is used as control medium. Three types of flow pattern of bulk water are
      used in the test to examine is effect on substrate transportation. From the
      kinetic test, it is found that the biomass fixed inside the sponge cube has
      biofilm characteristics. For conditions where the diffusion phenomenon is
      dominant, two layers whose yield constant are different to each other are
      confirmed from stoichiometric study. When the sponge cube is in the counter flow,
      it was found that the whole biomass fixed inside the medium works at the same
      time. It is considered that a certain amount of water is flowing through the
      medium when the sponge cube is exposed to counter flow. When the water is totally
      flowing through the sponge cube during the kinetic test by using type-3 reactor,
      a Michaelis-Menten type equation can represent the results of the kinetic test.

PMID- 12216661
TI  - Decay rate variability of active heterotrophic biomass.
AB  - Hypotheses of the ASM 1 model state that the specific respiration rate of
      heterotrophic active biomass is a constant. It thus becomes possible to assess
      the active heterotrophic biomass decay rate (bH) during starvation. The object of
      this study is to verify if the specific respiration rate of heterotrophic biomass
      remains constant throughout starvation, and if it is typical of global metabolic
      biomass activity, as proposed by the model hypotheses. The decay rate bH was
      evaluated using respirometric and enzymatic measurements. Measurement of bH
      through respirometry on various sludges varied between 0.28 and 0.76 d(-1).
      According to the enzyme and respirometric measurements carried out, a large
      portion of this value is related to enzymatic regulation. During starvation, when
      initial active biomass activity is high, down regulation of the respiratory chain
      results in a decrease in the specific heterotrophic active biomass respiration
      rate, thus creating an overevaluation of the decay rate as measured by
      respirometry. Thus a high decay rate used in the ASM 1 model could eventually
      lead to a poor forecast of biomass production.

PMID- 12216662
TI  - Effect of solids retention time on floc structure.
AB  - Correlative microscopy was applied to study the influence of solids retention
      time on activated sludge floc structure. Conventional optical microscopy revealed
      flocs at lower SRTs (4 and 9 days) to be irregular in shape while flocs at higher
      SRTs (16 and 20 days) had a more spherical and compact structure. Flocs were
      examined by environmental scanning electron microscopy (ESEM) and by transmission
      electron microscopy (TEM) coupled with energy-dispersive spectroscopy (EDS).
      Distinctive differences in floc structure and the arrangement of EPS were
      revealed. Flocs from higher SRTs were less hydrated and were found to possess a
      dense EPS layer that covers much of the surface. Extracellular osmiophilic
      granules present in these flocs indicate that the cells at the higher SRT may
      produce more lipid-like material. This EPS layer appears to decrease the floc
      surface roughness and protects the interior cells from disruption by changes in
      the external environment. Sludge flocs at higher SRTs were found to be physically
      more stable than those at lower SRTs.

PMID- 12216663
TI  - Real-time monitoring of ammonia-oxidizing activity in a nitrifying biofilm by
      amoA mRNA analysis.
AB  - Ammonia monooxygenase encoding mRNA (amoA mRNA) transcription in the wastewater
      treatment process was investigated using reverse transcription PCR (RT-PCR) as
      the model indicating specific function and activity in nitrifying processes. The
      dynamic response of amoA mRNA transcription and ammonia-oxidizing activity to the
      change of environmental conditions such as pH and concentration of ammonia was
      examined to determine the inductive factor and the inhibitor for amoA mRNA
      expression. Furthermore, we semiquantitatively investigated the response of amoA
      mRNA transcription to the pH fluctuation in a continuous fed nitrifying reactor.
      As a result, amoA mRNA oriented analysis enabled real-time assay of ammonia
      oxidizing activity within 2 h as a response time. In contrast, rRNA and amoA
      encoding DNA were constantly detected at almost the same amount throughout the
      experiment. mRNA transcription was regulated by the many environmental
      conditions: ammonia seems to be one of the strong inducers for transcription of
      amoA mRNA, whereas low pH seems to be a strong inhibitor. These factors
      simultaneously affected the mRNA transcription and enzymatic activity leading to
      the complex phenomena of ammonia-oxidizing activity and amoA mRNA transcription
      in the continuous feeding reactors.

PMID- 12216664
TI  - Quantifying the impact of wastewater micronutrient composition on in situ growth
      activity of Acinetobacter spp.
AB  - Batch growth studies with pure cultures of Acinetobacter johnsoniiT and
      Acinetobacter johnsonii strain 210 on various media formulations were used to
      examine the effects of micronutrient composition on the growth rate of microbial
      populations in wastewater treatment systems. On nutrient rich Luria-Bertani
      medium, both strains of A. johnsonii grew with a doubling time of approximately
      30 min. On a defined, minimal medium with acetate as the sole carbon source, the
      doubling time of A. johnsoniiT was 9.62 h and the doubling time of strain 210a
      was 2.6 h. Using a synthetic wastewater as a growth medium, the type strain had a
      doubling time of 56 h and strain 210a had a doubling time of 9.62 h. The
      concentration and redox state of iron appeared to be the principle growth
      limiting factors with higher doubling times occurring in media containing ferric
      iron as compared to ferrous iron. Additionally, grab samples from batch growth
      experiments were analyzed with oligonucleotide hybridization probes targeting the
      mature 16S ribosomal RNA (rRNA) and precursor 16S rRNA of Acinetobacter spp.
      Results showed that the precursor 16S rRNA levels responded more rapidly and to a
      greater extent than total 16S rRNA levels to changes in the micronutrient
      composition of the growth media. Precursor 16S rRNA levels increased in both
      strains when overnight cultures were diluted with fresh media and when
      micronutrient supplements were added to growing cultures. Our results show that
      the micronutrient composition of the influent wastewater can have a significant
      impact on the microbial community structure in wastewater treatment systems.

PMID- 12216665
TI  - Genomic fingerprinting of the 16S-23S gene spacer region suggests that novel
      Acinetobacter isolates are present in activated sludge.
AB  - The taxonomic status of the genus Acinetobacteris currently confused and the role
      of these organisms in activated sludge is poorly understood. Currently
      unidentified isolates of Acinetobacterfrom activated sludge were fingerprinted by
      making use of polymorphisms in their 16S-23S rDNA spacer region. The PCR
      amplified 16S-23S rDNA spacer region was digested with five different restriction
      enzymes to further differentiate between the isolates. The resulting band
      patterns were very diverse and the data suggests that the activated sludge
      isolates are different to the known genomic species of Acinetobacter which are
      predominantly clinical isolates. The results of this study imply the existence of
      yet unrecognised species of Acinetobacter in activated sludge.

PMID- 12216666
TI  - Competitive growth kinetics of Sphaerotilus natans and Acinetobacter anitratus.
AB  - Growth kinetics of Sphaerotilus natans and Acinetobacter anitratus (strain E932)
      in pure and mixed cultures were analysed. In order to determine mixed cultures
      biomass composition, a quantitative image analysis technique was developed. Pure
      culture studies showed that for dilution rates less than 0.188 h(-1), the
      filamentous micro-organism will predominate leading to bulking phenomena. By
      using the developed technique to determine biomass composition, mixed culture
      experiments showed that changes in the dilution rate modify the microbial
      composition of the biomass determining which micro-organism predominate. The
      stated equations that predict the predominance of S. natans at low dilution rates
      agree satisfactorily with the obtained results.

PMID- 12216667
TI  - Characteristics of bacterial populations responsible for uptake of amino acids in
      activated sludge acclimated to peptone.
AB  - Amino acids (AAs) are produced from the hydrolysis of proteins, which are the
      major biodegradable organic compounds in municipal sewage. The characteristics of
      bacterial populations responsible for the assimilation of thirteen AAs into
      activated sludge (AS) acclimated to peptone are investigated. The results are as
      follows. (1) The bacterial populations responsible for the uptake of AAs were
      partly aggregated in AS flocs. (2) The amounts of the bacterial populations
      responsible for the uptake of leucine, valine, isoleucine, histidine, threonine,
      lysine and glycine are limited in AS acclimated to peptone. (3) The bacterial
      populations responsible for the uptake of phenylalanine, leucine and lysine were
      different. (4) The amounts of bacterial populations responsible for the uptake of
      aspartate, arginine, alanine, glutamate and phenylalanine are not limited. (5)
      The functions of the assimilation of these AAs were induced in many bacterial
      cells as a result of the BOD determination methods applied to these pure AAs.

PMID- 12216668
TI  - Bulking sludge solved?!
AB  - At present there is still no final theory explaining the bulking of activated
      sludge. Previous investigations showed that the sludge settling properties become
      better and more stable when more plug flow conditions are implemented in
      wastewater treatment plants for biological nutrient removal. In this research the
      effect of the process configuration (4 wwtp with fully biological nutrient
      removal) on the sludge settling properties has been investigated. The results
      show that a separate anoxic reactor can not avoid the presence of LCFA for the
      growth of M. parvicella in the anaerobic reactor. A SVI < 120 ml/g could be
      achieved by: of a separate anoxic reactor with plug flow conditions, introducing
      of a strictly anaerobic reactor (UCT-modification), implementation of an extra
      anoxic/aerobic reactor, maintaining a high oxygen concentration (> 1.5 mg/l) and
      creating a low ammonium concentration (< 1 mg/l) in the aerobic reactor.

PMID- 12216669
TI  - Go or no go for gel entrapped nitrifiers? A Belgian case study.
AB  - In the coming years, as stricter environmental requirements are imposed, many
      European Union wastewater treatment plants (WWTP) need to be expanded and/or
      upgraded. This requires considerable investments. Optimising the renovation
      recourses can lead to significant savings. The use of entrapped nitrifying
      bacteria for upgrading of WWTP towards nutrient removal may be benificial. Long
      term pilot tests were performed to evaluate a so-called pellet reactor.
      Differences in performance and microbiological composition of classical activated
      sludge and the pellet reactor were investigated. FISH analyses showed (i) absence
      of Nitrobacter cells and (ii) high abundance of Nitrospira in the pilot reactors.
      Two Belgian WWTP make use of fine bubble aeration and could--theoretically-
      easily be renovated towards nitrogen removal using encapsulated nitrifiers.
      Financial aspects are commented on.

PMID- 12216670
TI  - Microbial evaluation of activated sludge and filamentous population at eight
      Czech nutrient removal activated sludge plants during year 2000.
AB  - The long-term project on the survey of filamentous microorganisms, which started
      in 1996, was finished in 2000 by the survey of eight Czech activated sludge
      plants with biological nutrient removal (BNR) systems. At all plants with
      enhanced biological nutrient removal, specific microbial population (mostly from
      the point of view of filaments occurrence), operational problems (presence of
      biological foaming, bulking) and plant operation were observed periodically and
      longer than 1 year. In our paper the relationship between the composition of
      activated sludge (especially filaments) consortia and modification of the process
      with nutrient removal is discussed. At the surveyed plants Type 0092 and
      Microthrix parvicella were identified as dominant Eikelboom filamentous types.

PMID- 12216671
TI  - Two stage activated sludge plants--influence of different operational modes on
      sludge bulking and nitrification.
AB  - Conventional two stage activated sludge plants often lack sufficient nutrient
      removal performance due to substrate limitation for denitrification in the second
      stage. For the extension of the Vienna Main WWTP a two stage concept has been
      developed and tested by means of a pilot plant (scale 1:10.000). The new concept
      enables the operation of two different modes: In BYPASS-mode a portion of the
      primary clarifier effluent is fed directly to the second stage; the HYBRID-mode
      includes the exchange of mixed liquor between the two stages; over the course of
      the pilot plant investigations it turned out that nutrient removal is strongly
      increased in comparison to conventional two stage mode, but the two modes of
      operation lead to different results with regard to the sludge quality and the
      nitrification performance. BYPASS mode yields a higher SVI in both stages and a
      lower nitrification performance in comparison to HYBRID mode. This is caused by
      the negative influence of the primary effluent on the biocoenosis of the second
      stage. Additionally, the reduced sludge loading of the first stage in this mode
      results in a higher sludge age which favours the growth of filaments (Microthrix
      and Nocardia). In HYBRID-mode the higher load of the first stage results in a
      lower sludge age, fatty components are metabolized and incorporated in the
      sludge, thus, the growth of filaments is significantly reduced. Additionally,
      nitrification inhibiting substances are degraded in the first stage, which
      results in a higher nitrification performance in the second stage.

PMID- 12216672
TI  - The influence of PAX-14 on activated sludge systems and in particular on
      Microthrix parvicella.
AB  - The amount of wastewater treatment plants (WWTP) dealing with solid separation
      problems has significantly increased since the new requirements of the EU
      Directive 271/91 on nutrient removal. In Flanders a number of the nutrient
      removal WWTP are affected by solid separation problems mostly attributed to
      Microthrix parvicella being the most common dominant species. The effect of
      dosing polyaluminium chloride (PAX-14) on activated sludge is illustrated for
      WWTP solids separation problems, in particular because of Microthrix parvicella.
      The effects of the addition of PAX-14 on the microbiology and the morphology of
      Microthrix parvicella were studied in 9 full-scale WWTP. PAX-14 succeeded in
      reducing high SVI-values and controlled foaming problems whenever caused by
      Microthrix parvicella. Laboratory trials have shown that the dosage of PAX-14
      should be less than 150 microL/L or 7 g Al3+/kg MLSS. At a dosage higher than 250
      microL/L, an increase of free bacteria and a decrease of the protozoa activity
      are observed. In full-scale, PAX-14 is dosed at a concentration of 1.5 to 4.5 g
      Al3+/kg MLSS. Before addition, the mixed liquor scum layer--if present--should be
      removed. In our experience, the dosing should last for at least 3 weeks. During
      the first week, no drastic changes occur. At the end of the first week, an
      increase of SS and SVI is possible. The SVI and scum start to decrease after 10
      to 15 days. The amount of filaments is reduced after 3 to 3 1/2 weeks. The
      morphological properties of Microthrix parvicella change, while other filaments
      such as Nostocoida limicola and Nocardia spp. are not affected. This study proves
      that PAX-14 is effective in controlling bulking and foaming problems at WWTPs
      when they are due to Microthrix parvicella. Prediction of when the SVI will
      decrease and when addition should be stopped is possible.

PMID- 12216673
TI  - Filamentous bacterial population dominance in activated sludges subject to
      stresses.
AB  - Evolution of a filamentous bacterial population was monitored on four wastewater
      treatment pilot plants subject to stresses which have consisted of oxygen
      deficiencies and/or loading shocks. Fluorescent in situ hybridization (FISH) was
      used to perform filaments identification and quantification. Results obtained on
      the different pilot plants have led us to conclude that independently of the
      nature of the stresses, a single filamentous bacteria species was involved in the
      increase of the sludge volume index associated to the filamentous growth. In
      addition, when serial stresses were used, substitutions in dominant filamentous
      populations occurred: if another filament began to proliferate it caused the
      regression of the one which was formerly dominant.

PMID- 12216674
TI  - Control of the growth of Microthrix parvicelle by using an aerobic selector-
      results of pilot and full scale plant operation.
AB  - A two-stage wastewater treatment plant experiences bulking sludge problems in
      winter, correlating with Microthixparvicella abundance. Pilot and full-scale
      studies of the use of an aerobic selector to control M. parvicella had little
      success, probably resulting from long chain fatty acid retention in foam at the
      tank surface. Initial pilot studies with reduced foam retention showed better
      results.

PMID- 12216675
TI  - Testing the effect of selectors in the control of bulking and foaming in full
      scale activated-sludge plants.
AB  - Selectors were operated at four full-scale activated sludge plants to control
      bulking and foaming problems due to filamentous microorganisms. Selector
      effectiveness was not related to reduction of biodegradable organic matter in the
      contact zone, but was related to soluble COD levels in selector effluent.
      Significant reductions in the numbers of filamentous m icroorganisms were
      reported.

PMID- 12216676
TI  - Microthrix parvicella foaming at the Fusina WWTP.
AB  - The Fusina WWTP receives civil and industrial wastewater from Venice and its
      hinterland. Its treatment capacity is in the range of 4,000-5,000 m3/h. In winter
      the Fusina WWTP is subjected to brown and viscous foams developed on the surface
      of the aeration basins and of the clarifiers. The microscopic observation of
      biological foams and activated sludge samples showed high concentration of the
      filamentous organism Microthrix parvicella. This paper investigates the growth of
      M. parvicella from January 1998 to January 1999 and relates it to foams developed
      on the aeration basins and clarifiers, to temperature, surfactants, BOD5, NH4,
      NO3, NO2, DO, PO4 and pH of the wastewater influent, to SVI and the other species
      of filamentous organisms of mixed liquor. The results demonstrate the strong
      connection of the foams developed with M. parvicella abundance, the synergic
      action with surfactants, the dependence of M. parvicella on temperature and no
      relation to the other chemical and physical parameters investigated.

PMID- 12216677
TI  - Treatment of easily biodegradable wastewater avoiding bulking sludge.
AB  - The presence of easily degradable compounds from food industries frequently leads
      to bulking problems. The paper describes a new process that has been developed
      for a dairy in Austria. Because of the increase in production the treatment plant
      receiving the wastewater up to now was not able to handle the increased loads.
      Therefore detailed studies for treatment alternatives have been undertaken which
      led to a completely new concept. The excess sludge of the urban treatment plant
      is contacted with the concentrated dairy waste in a separate contact tank. In
      this tank the easily degradable substrate from the industrial waste is mainly
      adsorbed to the biological sludge and after a mechanical dewatering transferred
      to the anaerobic digester where it yields an increased gas production. The
      filtrate of the dewatering process is completely free from biodegradable material
      and can without danger of bulking be fed to the aeration tank. The process has
      been in operation for more than one year and has fulfilled all expectations.

PMID- 12216678
TI  - A full scale application in the control of the filamentous bulking generated by
      Type 021 N F. thiothrix sp.
AB  - The presence of industrial effluent in the wastewater incoming to municipal
      activated sludge treatment plants sometimes causes bulking events. In order to
      control one of these events a strategy of bacterial selection was applied with an
      anoxic selector before the main oxidation basin utilising the screw pumps basin.
      The result of this work confirms what is reported in the literature about the
      possibility to utilize a metabolic control of some filamentous forms
      (particularly Type 021 N) with high organic load. The remedial action could be
      realized using already existing facilities, without any additional costs.

PMID- 12216679
TI  - Fighting foam with phages?
AB  - Seventeen (17) phages infective for the mycolata were isolated from six samples
      of activated sludge using 21 prospective hosts from the genera Dietzia, Gordonia,
      Nocardia, Rhodococcus, Tsukamurella and Mycobacterium. Their morphology indicated
      that they were all members of the viral family Siphoviridae, but they varied in
      the size of the icosahedral head and length of non-contractile tail, suggesting
      they were different. This was confirmed by host-range studies with 47 strains of
      mycolata, which showed that each phage had a unique host-range, and this was
      polyvalent in the majority (15/17) of cases, with 12 phages infective for hosts
      representing two or three of the genera Gordonia, Nocardia and Rhodococcus. The
      potential for use of these phages in the control of foaming and other
      applications is discussed.

PMID- 12216680
TI  - Gordonia (nocardia) amarae foaming due to biosurfactant production.
AB  - Gordonia amarae, a filamentous actinomycete, commonly found in foaming activated
      sludge wastewater treatment plants was investigated for its biosurfactant
      production capability. Soluble acetate and paringly soluble hexadecane were used
      as carbon sources for G. amarae growth and biosurfactant production in laboratory
      scale batch reactors. The lowest surface tension (critical micelle concentration,
      CMC) of the cell-free culture broth was 55 dynes/cm when 1,900 mg/L acetate was
      used as the sole carbon source. The lowest surface tension was less than 40
      dynes/cm when either 1% (v/v) hexadecane or a mixture of 1% (v/v) hexadecane and
      0.5% (w/v) acetate was used as the carbon source. The maximum biomass
      concentration (the stationary phase) was achieved after 4 days when acetate was
      used along with hexadecane, whereas it took about 8 days to achieve the
      stationary phase with hexadecane alone. The maximum biosurfactant production was
      3 x CMC with hexadecane as the sole carbon source, and it was 5 x CMC with the
      mixture of hexadecane and acetate. Longer term growth studies (approximately 35
      days of culture growth) indicated that G. amarae produces biosurfactant in order
      to solubilize hexadecane, and that adding acetate improves its biosurfactant
      production by providing readily degradable substrate for initial biomass growth.
      This research confirms that the foaming problems in activated sludge containing
      G. amarae in the activated sludge are due to the biosurfactant production by G.
      amarae when hydrophobic substrates such as hexadecane are present.

PMID- 12216681
TI  - An investigation into studying of the activated sludge foaming potential by using
      physicochemical parameters.
AB  - This paper examines how the physicochemical characteristics of the solids are
      related to foam formation and describes how the foaming potential of full-scale
      plants can be assessed. The relations among activated sludge and biological foam
      hydrophobicity, scum index, aeration tank cover and filamentous population are
      evaluated. Individual parameter comparison reveals the scumming intensity can be
      estimated only on the assumption that foams is already established. None of the
      above mentioned characteristics can be reliably used to predict the foaming
      episodes at wastewater treatment plants.

PMID- 12216682
TI  - Are filamentous mycolata important in foaming?
AB  - In a previous study, we showed that there was a significant increase in mycolata
      numbers associated with foaming events at a wastewater treatment site possessing
      three activated sludge plants. In this paper, we demonstrate that branched
      filamentous mycolata were a minor proportion of the mycolata morphotypes present
      in those activated sludge plants, accounting for less than 21% of the mycolata
      population in the mixed liquor and foam samples examined. In most samples
      examined, the number of filamentous mycolata was negligible compared to the
      number of other mycolata morphotypes present. Furthermore, filamentous mycolata
      did not contribute to any of the significant differences in mycolata
      concentration observed between foaming and non-foaming situations (P<0.01). These
      findings suggest that conventional microscopic examination for monitoring
      mycolata populations in foaming plants may be misleading and should be used with
      caution.

PMID- 12216683
TI  - Filamentous micro-organisms observed in industrial activated sludge plants.
AB  - As part of the EU-sponsored MACOBS (Monitoring and Control of Bulking Sludge
      through Molecular Probe Assays) project, the size and the composition of the
      filamentous population in 73 industrial activated sludge plants, were
      investigated. The inventory included plants in Denmark, Germany, Italy and The
      Netherlands. Large filamentous populations were present in about 60% of the
      plants, which means that bulking of activated sludge, which is no longer a
      serious problem in modern domestic nutrient removal plants, still occurs
      frequently in industrial treatment plants. The filamentous micro-organisms
      present were identified/described by "traditional" methods, based on their
      morphological features and several staining techniques, and by the application of
      molecular probes (FISH: Fluorescent In Situ Hybridisation). Nine species specific
      probes were available when the project started, nine new probes have been
      developed during the project. Fifty nine different filamentous species were
      observed in the samples, including ca. 40 species that have not been described so
      far. The unknown species are denoted as Type Ind-1, 2, 3, etc. Probes are now
      available for the identification of about 17 species. Further research aimed at
      developing additional probes will be necessary in order to establish which
      species distinguished provisionally are identical, viz. morphotypes of the same
      filamentous organism.

PMID- 12216684
TI  - The effect of C/N ratio on ammonia oxidising bacteria community structure in a
      laboratory nitrification-denitrification reactor.
AB  - A laboratory scale reactor operated as a single sludge, denitrification
      nitrification bioreactor (DNB), was fed a synthetic wastewater. The effect of the
      C/N ratio of the influent on the structure of beta-proteobacterial autotrophic
      ammonia-oxidizing bacterial (AOB) communities was determined by DGGE analysis of
      16S rRNA gene fragments amplified using a range of AOB-selective primers.
      Fluorescence in situ hybridisation (FISH) was used to determine quantitative
      changes in the AOB communities. When operated at a C/N ratio of 2 the DNB was
      effective in nitrogen removal and nitrification was measured at approximately 1.0
      mg NH4+-N/g dry wt/h. Altering the C/N ratio to 5 resulted in a 50% reduction in
      nitrification rates. Nitrification was restored to its original level when the
      C/N ratio was returned to 2. AOB were detected by DGGE analysis of samples from
      the DNB under all operating conditions but the changes in C/N ratio and
      nitrification rates were accompanied by changes in the community structure of the
      AOB. However, quantitative FISH analysis indicated that beta-proteobacterial AOB
      were only present in high numbers (ca. 10(8) cells/ml) under the original
      operating conditions with a C/N ratio of 2. Beta-proteobacterial AOB could not be
      detected by FISH when the C/N ratio was 5. When nitrification activity was
      restored by returning the C/N ratio to 2, beta-proteobacterial AOB were still not
      detected and it is likely that either beta-proteobacterial AOB were not
      responsible for ammonia oxidation or that beta-proteobacterial AOB that did not
      contain the target sites for the range of 4 AOB selective probes used, were
      present in the reactor.

PMID- 12216685
TI  - Biological iron oxidation-reduction and the effects on sulfur oxidation
      reduction, denitrification and poly-P accumulation in an anaerobic-oxic activated
      sludge.
AB  - Iron oxidation and reduction were examined using the activated sludge from a
      municipal plant. Iron contents of the activated sludge were 1-2%. Iron oxidation
      rates were correlated with the initial iron concentrations. Iron reducing rates
      could be described by the Monod equation. The effects of iron reducing bacteria
      on sulfate reduction, denitrification and poly-P accumulation were examined. Iron
      reduction suppressed sulfate reduction by competing with hydrogen produced from
      protein. Denitrification was outcompeted with iron reduction and sulfate
      reduction. These phenomena could be explained thermodynamically. Poly-P
      accumulation was also suppressed by denitrification. The activity of iron
      reduction was relatively high.

PMID- 12216686
TI  - Molecular monitoring of bulking sludge in industrial wastewater treatment plants.
AB  - Fluorescent In Situ Hybridisation (FISH) was used to monitor the presence of
      filamentous microorganisms in industrial wastewater treatment plants (WWTPs).
      Monitoring with a restricted set of FISH probes in WWTPs from potato industry
      showed growth and decline of Thiothrix populations that could be linked to
      operational procedures. In a follow up project new FISH probes were developed for
      filamentous bacteria in industrial WWTPs and 70 WWTPs were analysed for presence
      of these filaments. Several newly described species of filamentous bacteria
      appear to be common and dominant in industrial WWTPs. Monitoring of a WWTP from
      textile industry showed growth and decline of one of these organisms when
      operational conditions in the plant were varied. The present paper demonstrates
      that bulking sludge in industrial wastewater treatment plants can effectively be
      monitored using a combination of standard chemical analyses and the FISH
      technique.

PMID- 12216687
TI  - Application of oligonucleotide probes for the detection of Thiothrix spp. in
      activated sludge plants treating paper and board mill wastes.
AB  - Filamentous bacteria belonging to the genus Thiothrix were detected in activated
      sludge samples using the fluorescent in situ hybridisation (FISH) technique. A
      16S rRNA-targeted oligonucleotide probe was developed for the detection of
      members of the T. fructosivorans group, and the performance of probe TNI for the
      detection of Thiothrix nivea group was enhanced by using an unlabeled competitor.
      A set of 5 probes covering all phylogenetic groups of Thiothrix were used to
      examine samples taken from selected activated sludge plants treating paper and
      board mill wastes. Members of the T. eikelboomii group formed the predominant
      filamentous bacterial population in plants experiencing poor sludge
      settleability, whereas members of the T. nivea group were commonly found but not
      dominantly in the remaining plants. Members of the T. fructosivorans group were
      not detected at any significant level in any of the samples. The distribution of
      the main Thiothrix types remained unchanged throughout the investigation period.
      It was evident that mixed populations of Thiothrix spp. were present in all
      activated sludge samples investigated, the observed differences were in the
      relative abundance of the various groups. These findings were supported by the
      results obtained using conventional microscopy.

PMID- 12216688
TI  - Anaerobic sequencing batch reactor as initiating stage in complete
      pentachlorophenol biodegradation.
AB  - Biodegradation of pentachlorophenol (PCP) has been studied in a sequence of two
      completely mixed reactors. Investigation on the first anaerobic sequencing batch
      reactor (AnSBR) is discussed in detail in this paper. Key technological and
      microbiological features were studied: two different types of adaptation process
      of anaerobic sludge towards PCP detoxication; the influence of the sludge
      concentration upon the rate of PCP biodegradation; minimum retention time for PCP
      degradation in dependence on the PCP concentration; modeling of the PCP
      degradation process; effluent COD and SS concentrations; changes in the micro-
      and macrostructure of the sludge during acclimatization process.

PMID- 12216689
TI  - The effect of reactor configuration and operational mode on Microthrix parvicella
      bulking and foaming in nutrient removal activated sludge systems.
AB  - Three bench-scale nutrient removal activated sludge units were used to examine
      the effect of the reactor configuration and the intermittent aeration mode on the
      growth of Microthrix parvicella. According to the results, the plug flow
      configuration seems to achieve satisfactory Microthrix parvicella control. The
      imposed concentration gradient for both RBCOD and SBCOD creates a selective
      advantage for the floc forming bacteria throughout the system (both the anoxic
      and oxic zones) and limits Microthrix parvicella growth. In terms of the
      operational mode, the intermittent aeration CSTR nutrient removal system promotes
      the growth of M. parvicella and deteriorates the settling characteristics of the
      activated sludge.

PMID- 12216690
TI  - "Microthrix parvicella": a new approach for kinetic and physiological
      characterization.
AB  - Two strains of "Microthrix parvicella" (RN1 and 4B strains) have been
      physiologically and kinetically characterized by utilizing a new technique
      particularly suitable for slow growing bacteria. The proposed method is based on
      the Total Extended Filament Length (TEFL) measure on filaments grown on agar
      surfaces. This allows us to study more easily and rapidly slow growing bacteria
      under many different conditions without altering the growth environment during
      the test. "Microthrix parvicella" appears to have versatile physiological
      capabilities allowing effective competition against other bacteria in the complex
      biocenosis of activated sludge. Main peculiarities of this organism are its
      storage capabilities under an aerobic/anoxic/anaerobic reaction environment, the
      resistance to long periods of anoxic/anaerobic conditions, the possibility of
      growing with appreciable kinetics at very low temperatures. In the kinetic
      characterization low Ks values have been observed; this finding supports the
      assumption that "Microthrix parvicella" is a "Ks- strategist" with high substrate
      affinity. Kinetics tests performed in a mixed population of activated sludge
      bacteria and on pure culture of filaments isolated from the same sludge sample
      showed that no beneficial effect on the growth rates of "Microthrix parvicella"
      seems attributable to the presence of activated sludge. This last result confirms
      the validity of pure culture studies for this microorganism and the reliability
      of physiological and kinetic data so evaluated in describing real systems.

PMID- 12216691
TI  - Microthrix parvicella, a specialized lipid consumer in anaerobic-aerobic
      activated sludge plants.
AB  - The in situ physiology of the filamentous bacterium Microthrix parvicella was
      investigated in anaerobic-aerobic dynamic phases in activated sludge with focus
      on the uptake of long chain fatty acids (LCFA) and growth. When 14C-labeled oleic
      acid was added to activated sludge with an excessive growth of M. parvicella,
      only little 14C-CO2 was produced under anaerobic conditions while a lot was
      produced under aerobic conditions. Microautoradiographic studies revealed that M.
      parvicella took up oleic acid under both anaerobic and aerobic conditions, while
      only a few floc formers were able to take it up under anaerobic conditions.
      Extraction and separation of the radioactive biomass into different lipid
      fractions showed that the oleic acid was stored mainly as neutral lipids under
      anaerobic conditions, whereas conversion to membrane phospholipids occurred
      almost exclusively under aerobic conditions, indicating growth. The surface
      properties of M. parvicella and other bacteria were characterized by hydrophobic
      fluorescent microspheres, which showed that M. parvicella was relatively
      hydrophobic. Furthermore, a surface-associated extracellular lipase activity was
      observed, indicating the ability of M. parvicella to degrade lipids near the
      filament surface. The results support the hypothesis that uptake and storage of
      LCFA as lipids under anaerobic conditions provide an effective competition
      strategy against bacteria that can only take up LCFA under aerobic conditions.
      Thus, M. parvicella seems to be a specialized lipid consumer with a physiological
      potential analogous to PAOs and GAOs being able to take up LCFA (but not short
      chain fatty acids or glucose) under anaerobic conditions and subsequently use the
      storage material for growth when nitrate or oxygen are available as electron
      acceptors.

PMID- 12216692
TI  - Dispelling the "Nocardia amarae" myth: a phylogenetic and phenotypic study of
      mycolic acid-containing actinomycetes isolated from activated sludge foam.
AB  - Right-angle branched filaments and rods micromanipulated from activated sludge
      foam and mixed liquor were identified as putatively novel members of the genera
      Gordonia, Mycobacterium and Rhodococcus using a combination of chemical,
      molecular and morphological data. Pyrolysis mass spectrometric analyses of
      gordoniae isolated in both the present and a previous study revealed pyro-groups,
      distinct from validly described Gordonia species, which could be equated with
      those based on morphological properties and 16S rDNA data. Putative gordoniae
      assigned to one of these groups were found to be closely related to strains
      currently identified as "Rhodococcus australis". These strains were also found to
      have properties consistent with their classification in the genus Gordonia. The
      results of this study highlight the limitations of the microscopic approach to
      filament identification and cast further doubt on the view that foaming can be
      attributed to members of one or a few Nocardia species.

PMID- 12216693
TI  - Phylogenetic and physiological characterization of a "Nostocoida limicola"-like
      organism isolated from activated sludge.
AB  - Ten strains of "Nostocoida limicola"-like organisms were isolated from a
      municipal wastewater treatment plant with minor industrial effluent. The near
      complete 16S rDNA sequences were determined for four strains to analyze the
      position of the organisms within the phylogenetic tree. All four isolates showed
      the same 16S rRNA sequence and cluster within the green non sulfur bacteria.
      Hybridization with oligonucleotide probe AHW183 designed complementarily to
      diagnostic regions of the 16S rRNA sequences showed a positive reaction with all
      isolated strains. Hybridization of activated sludge samples with probe AHW183
      indicates the filamentous "Nostocoida limicola"-like bacteria commonly to occur
      inside the sludge flocs and to hardly be detected within the flocs without a
      specific staining. On HA-medium all strains grow as long coiled, unbranched and
      unsheathed filaments which usually stain gram positive and show a variable
      Neisser reaction. The isolates grow well in liquid HA-medium at COD values
      between 1 to 4 g O2 h(-1) and a pH range from 6.0-7.8. No growth is detected in
      liquid R2A-medium and several synthetic mineral salts media containing various
      carbon and nitrogen sources.

PMID- 12216694
TI  - Phylogenetic analysis and in situ identification of "Nostocoida limicola"-like
      filamentous bacteria in activated sludge from industrial wastewater treatment
      plants.
AB  - The diversity of filamentous bacteria present in industrial wastewater treatment
      plants was analysed by a combination of classical and molecular-biological
      approaches. Many unknown filamentous bacteria were observed in about 80 screened
      activated sludge samples from different industries with sometimes severe bulking
      sludge problems. A special focus was paid to filaments which resembled
      "Nostocoida limicola", a filamentous bacterium which was found to be present in
      many WWTPs. These filamentous bacteria are hardly cultivable and only one strain
      was obtained and maintained in co-culture with a yeast. The 16S rRNA sequences of
      several other "Nostocoida limicola"-like filamentous bacteria from different
      sludge samples were obtained by micromanipulation and different molecular
      biological methods. The sequences were phylogenetically analyzed and specific
      molecular probes were developed and applied. The results clearly demonstrate that
      "Nostocoida limicola"-like filaments from industrial WWTPs are different from all
      other "Nostocoida limicola" types investigated so far. Our strains are affiliated
      to the alpha-subclass of Proteobacteria.

PMID- 12216695
TI  - Computer technology applications in industrial and organizational psychology.
AB  - This article reviews computer applications developed and utilized by industrial
      organizational (I-O) psychologists, both in practice and in research. A primary
      emphasis is on applications developed for Internet usage, because this "network
      of networks" changes the way I-O psychologists work. The review focuses on
      traditional and emerging topics in I-O psychology. The first topic involves
      information technology applications in measurement, defined broadly across levels
      of analysis (persons, groups, organizations) and domains (abilities, personality,
      attitudes). Discussion then focuses on individual learning at work, both in
      formal training and in coping with continual automation of work. A section on job
      analysis follows, illustrating the role of computers and the Internet in studying
      jobs. Shifting focus to the group level of analysis, we briefly review how
      information technology is being used to understand and support cooperative work.
      Finally, special emphasis is given to the emerging "third discipline" in I-O
      psychology research-computational modeling of behavioral events in organizations.
      Throughout this review, themes of innovation and dissemination underlie a
      continuum between research and practice. The review concludes by setting a
      framework for I-O psychology in a computerized and networked world.

PMID- 12216696
TI  - Using the internet for organizational research: a study of cynicism in the
      workplace.
AB  - The Internet can be a valuable data collection tool for organizational psychology
      researchers. It can be less expensive than traditional paper-and-pencil survey
      methods, and the potential pool of participants is much larger. In addition, it
      can be used in situations where traditional data collection methods are not
      feasible, such as research involving sensitive issues such as negative employee
      attitudes or deviant behaviors at work. In this study, we examined the
      organizational attitudes of employees from various companies using (a) a snowball
      sample, who completed a traditional paper and pencil survey (n = 135), and (b) a
      sample recruited over the Internet, who completed an on-line survey (n = 220).
      Participants in both the non-Internet and the Internet group were asked to
      describe a negative incident involving their company, and answer a number of
      questions regarding how they felt about their company and how they behaved toward
      their company following the negative event. They also completed measures of
      organizational cynicism and job satisfaction. The two groups were compared on
      demographic characteristics and on their attitudes toward their organization.
      There were very few demographic differences between the two groups. The Internet
      group tended to be more cynical and to judge their organization more harshly than
      the non-Internet group; however, the response patterns of both groups were
      similar. These results suggest that, when used with caution, the Internet can be
      a viable method of conducting organizational research.

PMID- 12216697
TI  - Unsubscribe, pleeezz!!!: management and training of media competence in computer
      mediated communication.
AB  - Computer-mediated communication (CMC) has created a new communication divide.
      Mostly, this division is due to technical and access problems. Overlooked is yet
      another divide in terms of user communication competence. This contribution
      focuses on media competence based on theories about communication competence and
      theories about CMC. Two field studies are presented: an analysis of a virtual
      seminar chat communication (22 participants, 3 weeks' duration) and an analysis
      of unsubscribe-failures within 2 years of a German mailing list (average of 1,000
      subscriptions). Data from both studies reveal that help-seeking CMC users with
      low media-specific competence experience setbacks in terms of interpersonal
      relations and information gathering. There is a spiral of neutral to negative
      reactions and an increase in stress and aggression-related language in the
      reaction of the addressed peers. From the perspective of external raters, we
      found a contraintuitive result: The style, content, and wording of the message of
      the respondent is considered as an indicator for a less competent and socially
      attractive person behind the follow-up message than those of the initial message.
      On the one hand, media experts are needed and appreciated as technical problem
      solvers; on the other hand, they might be perceived as socially narrow-minded
      freaks who are less interested in the task itself than in CMC-based task
      completion. This leads to the question of how sensibility for the social context,
      task orientation, and media competence can be combined (and trained for) in one
      person. Two competence trainings for text-based synchronous and asynchronous
      communication are introduced as interventions.

PMID- 12216698
TI  - Validation of a new scale for measuring problematic internet use: implications
      for pre-employment screening.
AB  - The current study introduced a theory-driven, multidimensional measure of
      problematic Internet use: the Online Cognition Scale (OCS). Undergraduate
      students (n = 211) in an industrial/organizational psychology course completed
      the OCS, along with measures of procrastination, rejection sensitivity,
      loneliness, depression, and impulsivity. A confirmatory factor analysis indicated
      that problematic Internet use consists of four dimensions: diminished impulse
      control, loneliness/depression, social comfort, and distraction. As hypothesized,
      the OCS predicted all of the study variables in the expected directions.
      Representing a departure from previous research in this area, the current article
      focused on procrastination, impulsivity, and social rejection as key elements of
      problematic Internet use. Furthermore, interactive applications (e.g., chat) were
      most related to problematic Internet use, and scores on the OCS predicted being
      reprimanded at school or work for inappropriate Internet use. As a result, the
      utility of the OCS for both clinical assessment of Internet addiction and as an
      organizational preemployment screening measure to identify potential employees
      who are likely to abuse the Internet in the workplace (also known as
      "cyberslacking") were discussed.

PMID- 12216699
TI  - Lost in cyberspace: the web @ work.
AB  - Most U.S. businesses provide Internet access for their employees. The current
      study surveyed representatives from 224 organizations on issues related to
      Internet abuse. Nearly 70% of companies surveyed had more than half of their
      employees online. Almost all companies had Internet access policies (IAP) in
      place (82.6%), outlining appropriate and inappropriate use of the Internet in the
      workplace. Despite IAPs, U.S. businesses are facing a severe problem. More than
      60% of companies had disciplined-and more than 30% had terminated--employees for
      inappropriate use of the Internet. Accessing pornography, online chatting,
      gaming, investing, or shopping at work were the leading causes for disciplinary
      action or termination. Many companies were not concerned about the severity of
      the problem (49.6%) and/or had done very little to enforce their IAPs (59.4% use
      self or managerial oversight, and only 37.5% use filtering software).

PMID- 12216700
TI  - Employee Internet management: current business practices and outcomes.
AB  - This paper empirically examines emergent business practices that attempt to
      reduce and control employee Internet misuse and abuse. Over a 6-month period, 52
      web-administered surveys were collected. Respondents ranged from human resource
      managers to company presidents. Data were stored in a database management system
      and analyzed utilizing statistical measures. Monitoring efforts and policy
      development issues are examined against critical incidents of employee Internet
      abuse. The analysis also includes a rank ordering of the types of Internet
      applications that were perceived as most problematic or abused. Types of
      applications abused include electronic mail, adult web sites, online gaming, chat
      rooms, stock trading, and so on. Moreover, company size and years online are
      examined. Overall, this research will assist organizations in implementing
      effective corporate initiatives to improve employee Internet management
      practices.

PMID- 12216701
TI  - What makes an online relationship successful? Clues from couples who met in
      cyberspace.
AB  - From a larger study of 68 couples who met online, eight couples were chosen as
      cases representing the sample to illustrate two kinds of outcomes: "successful,"
      continuing couples, or "unsuccessful," relationships that ended. All respondent
      accounts from questionnaire data, interviews, and e-mail correspondence between
      partners were closely examined. Four factors emerged which seemed to
      differentiate among the two types of relationships begun online: (1) meeting
      place, where they first encountered each other online; (2) obstacles, barriers to
      getting together overcome by the couples, such as distance and previous
      relationships; (3) timing, period spent writing or talking before meeting
      offline, and how intimate they became before meeting offline; and (4) conflict
      resolution, ability of the people to resolve problems in communication. People
      who first met in places based upon common interests, who communicated for long
      periods of time before meeting offline without too much intimacy, who worked
      through barriers to becoming closer, and who negotiated conflict well tended to
      stay together. Future research and analysis can further determine how the process
      of forming and maintaining successful relationships begun online compares to
      those started offline.

PMID- 12216702
TI  - Solicitation by e-mail and solicitor's status: a field study of social influence
      on the web.
AB  - Personal information is scarce in computer-mediated communication. So when
      information about the sender is attached with his or her e-mail, this could
      induce a powerful effect toward the receptor. Two experiments were carried out
      where males and females were solicited by e-mail to respond to a survey on their
      foods habits. In the first experiment, students were solicited whereas, in the
      second experiment, people taken at random in various e-mails lists were
      solicited. The questionnaire was an HTML form attached with the e-mail. The
      signature of the solicitor was presented as of a high status (a scientist) or of
      a mid status (an undergraduate student). Results show that, in both experiments,
      subjects agreed more favorably to the request when the solicitor was of high
      status. The importance of social information on computer-mediated communication
      is used to explain such results.

PMID- 12216703
TI  - Diet restriction impairs extracellular signal-regulated kinase activation of
      peritoneal exudative cells after N-formyl-methionyl-leucyl-phenylalanine
      stimulation in a murine peritonitis model.
AB  - BACKGROUND: Phosphorylation of extracellular signal-regulated kinase (ERK)
      enhances various inflammatory responses in immune cells. It is unknown whether
      dysfunction of immune cells during malnutrition is attributed to derangement of
      ERK activation. METHODS: Male Institute of Cancer Research (ICR) mice received
      chow (146 g/kg per day, ad libitum or 36.5 g/kg per day, diet-restricted) for 7
      days. Mice (n = 55) were given 6.5 mg/kg of an ERK inhibitor (PD98059) or vehicle
      intraperitoneally (IP), at 2 hours before cecal ligation and puncture (CLP).
      Survival was observed up to 60 hours. Detection of phosphorylated ERK (pERK) in
      the peritoneal exudative cells (PECs) was done as follows. In a separate study,
      PECs were harvested by peritoneal lavage 2 hours after an IP injection of 1%
      glycogen. PECs were incubated with or without 100 nmol/L N-formyl-methionyl
      leucyl-phenylalanine (fMLP) for 1 minute. PEC ERK activation was detected with
      Western blot analysis (n = 38), by densitometric quantification, and with a laser
      scanning cytometer (LSC; n = 13). Subpopulations of PECs were determined by
      Wright-Giemsa staining. Unstimulated pERK expression was normalized to 100% for
      Western blot analysis. RESULTS: Diet restriction reduced survival after CLP
      compared with the ad libitum mice. ERK inhibition showed no effect on survival in
      diet-restricted mice but reduced survival in ad libitum mice. There were no
      differences in subpopulations of PECs 2 hours after glycogen injection between
      the groups. Western blot analysis revealed that fMLP stimulation significantly
      increased the phosphorylation of ERK1/2 in PECs from the ad libitum group (ERK1,
      199 +/- 41%; ERK2, 211 +/- 49%; p < .03) but not in those from diet-restricted
      mice (ERK1, 98 +/- 10%; ERK2, 91 +/- 9%). Mean fluorescence intensity (MFI) of
      pERK in PECs obtained by LSC was significantly elevated after fMLP in the ad
      libitum group (from 19.4 +/- 1.5 MFI to 22.4 +/- 1.2 MFI; p < .05) but did not
      change in the diet-restricted group (from 19.4 +/- 1.8 MFI to 19.1 +/- 1.5 MFI).
      CONCLUSIONS: ERK activation is essential for survival in this murine sepsis
      model. Impaired ERK activation of PECs may, at least in part, impair host defense
      during malnutrition.

PMID- 12216704
TI  - Mucosal immunity preservation with bombesin or glutamine is not dependent on
      mucosal addressin cell adhesion molecule-1 expression.
AB  - BACKGROUND: Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is an adhesion
      molecule that directs naive T and B cells into Peyer's patches for sensitization
      and distribution to intestinal and extraintestinal sites. With no enteral
      stimulation, its expression drops rapidly in association with reduced Peyer's
      patch cell populations and increases rapidly with reinstitution of enteral
      feeding. Because both glutamine (GLN) and bombesin (BBS) preserve mucosal
      immunity, this study examined whether they preserve MAdCAM-1 expression. METHODS:
      In 2 separate experiments, animals were randomized to IV cannulation with chow,
      total parenteral nutrition (TPN), and (experiment 1) 15 microg/kg BBS 3 times per
      day or (experiment 2) an isocaloric, isonitrogenous 2% GLN-supplemented solution.
      After 5 days of feeding, MAdCAM-1 expression in Peyer's patches, spleen, and
      intestine was measured using a dual radiolabeled monoclonal antibody technique.
      RESULTS: MAdCAM-1 expression was not significantly improved from TPN levels
      either with BBS or GLN supplementation. Levels of MAdCAM-1 expression remained
      unchanged in non-Peyer's patch sites. CONCLUSIONS: Although MAdCAM-1 is
      considered the gateway molecule for cell entry into mucosal immunity, this does
      not seem to be the mechanism for mucosal immunity preservation in nonenterally
      fed mice receiving bombesin or glutamine.

PMID- 12216705
TI  - Relative influence of glucose and insulin on peripheral amino acid metabolism in
      severely burned patients.
AB  - BACKGROUND: Protein catabolism and glucose intolerance are prominent in
      critically injured patients. The objective of this study was to assess if glucose
      or insulin availability influences the extent of protein catabolism in
      hypermetabolic patients. METHODS: Amino acid net balance from the leg was
      quantitated in 6 severe burn victims. Furthermore, whole body and leg protein
      kinetics were assessed with 2H5 phenylalanine and 15N alanine. Measurements were
      obtained after a 9-hour fast, during an IV glucose infusion (30 micromol/kg per
      minute), and during a hyperinsulinemic (500 mIU/kg per minute) euglycemic clamp.
      RESULTS: Compared with fasting values, the administration of glucose resulted in
      a significantly increased efflux of amino acids from the leg. In contrast,
      insulin administration significantly decreased the cumulative net efflux of amino
      acids. During hyperinsulinemia, isotopic measurements demonstrated a significant
      decrease in alanine appearance and an increase in phenylalanine disappearance
      into the leg. CONCLUSIONS: These findings demonstrate that in critically injured
      patients, acute hyperglycemia increases muscle catabolism despite an endogenous
      insulin response. In contrast, exogenous insulin given in sufficient amount
      impedes muscle protein loss. The mechanism for this anabolic effect of insulin
      may vary between different amino acids.

PMID- 12216706
TI  - Effect of upper extremity posturing on measured resting energy expenditure of
      nonambulatory tube-fed adult patients with severe neurodevelopmental
      disabilities.
AB  - PURPOSE: To ascertain the effect of upper extremity posturing on measured resting
      energy expenditure (MEE) for patients with severe neurodevelopmental
      disabilities. METHODS: Twenty-four nonambulatory adult patients with severe
      neurodevelopmental disabilities referred for evaluation of enteral tube feeding
      and who had a steady-state MEE performed were studied. Steady-state indirect
      calorimetry measurements were done through a canopy system. Patients were
      stratified according to the topography of their neuromotor impairment and motor
      function as having either fixed upper extremity contractures (Fixed UE) or with
      preservation of limited functional and nonfunctional upper extremity movement
      (Preserved UE). RESULTS: Despite a similar age, weight, height, and gender
      distribution between groups, those patients with Fixed UE (n = 13) had a
      significantly lower MEE than those with Preserved UE (n = 11): 893 +/- 91 versus
      1144 +/- 262 kcal/d (p < .01), respectively. The Harris-Benedict equations'
      predicted energy expenditures were similar to MEE for patients with Preserved UE
      (1212 +/- 156 versus 1144 +/- 262 kcal/d, respectively, p = N.S.). Patients with
      Fixed UE had a significantly lower MEE than predicted by the Harris-Benedict
      equations (893 +/- 91 versus 1128 +/- 123 kcal/d, respectively, p < .01)
      CONCLUSIONS: Patients with fixed upper extremity contractures have a
      significantly lower MEE than those with preserved upper extremity movement. MEE
      for nonambulatory tube-fed adult patients with severe neurodevelopmental
      disabilities and fixed upper extremity contractures is significantly lower than
      predicted by the Harris-Benedict equations.

PMID- 12216707
TI  - Omega-3 fatty acid supplementation reduces tumor growth and vascular endothelial
      growth factor expression in a model of progressive non-metastasizing malignancy.
AB  - BACKGROUND: Omega-3 fatty acids, the principal component of fish oil, have been
      demonstrated to have antiinflammatory properties. The role of eicosapentaenoic
      acid (EPA) supplementation for cancer patients is currently under investigation;
      however, the mechanisms of EPA activity have not been defined. The purpose of
      this study was to characterize tumor-specific and treatment-specific effects of
      supplemental dietary EPA in an animal model of progressive malignancy. METHODS:
      Fischer 344 rats (200-250 g) underwent flank implantation of the
      methycholanthrene (MCA)-induced fibrosarcoma on day 0. Rats were randomly divided
      into 3 treatment groups on day 13: EPA (1 mL, 5.0 g/kg per day) + 10 IU vitamin
      E; corn oil (1 mL) + 10 IU vitamin E, and saline (1 mL) + 10 IU vitamin E
      (vitamin E was used to prevent fatty acid oxidation). On day 14, gavage feeding
      was started and was continued through day 28. The animals were killed on day 29,
      and the tumors were removed. The tumors were weighed and divided by the tumor
      free carcass weight to obtain percentage of tumor volume, and the livers were
      flash frozen. Vascular endothelial growth factor-alpha (VEGF-alpha) and cyclo
      oxygenase 2 (COX-2) mRNA were measured by reverse transcription-polymerase chain
      reaction (RT-PCR). RESULTS: EPA rats had significant reductions in tumor volume
      compared with isocaloric corn oil and control saline animals (25%, p < .01 and
      33%, p < .01, respectively). Rats receiving EPA demonstrated decreased VEGF-alpha
      mRNA levels (0.023 +/- 0 0.001) compared with those receiving corn oil (0.129 +/-
      0.047) or saline (0.150 +/- 0.026; p < .05). CONCLUSIONS: These data demonstrate
      that EPA supplementation inhibits tumor growth, potentially through alterations
      in the expression of the pro-angiogenic VEGF-alpha. The mechanism(s) of EPA as an
      inhibitor of tumor-related angiogenic growth factors may be associated with COX-2
      enzyme fatty acid metabolism and merits further study.

PMID- 12216708
TI  - Are dietary fats anti-tumor agents?

PMID- 12216709
TI  - Eicosapentaenoic acid supplementation reduces tumor volume and attenuates
      cachexia in a rat model of progressive non-metastasizing malignancy.
AB  - BACKGROUND: Eicosapentaenoic acid (EPA) has been shown to have anti-inflammatory
      and tumor growth inhibitory effects clinically and experimentally; evidence also
      supports the role of EPA in attenuating cancer-associated weight loss, but the
      mechanisms of these effects remain to be defined. As the liver plays a central
      role in modulating nutritional status and the cachexia syndrome, we examined the
      liver and nutritional parameters indicative of cachexia along with the tumor
      volume in response to oral EPA supplementation in a rat model of progressive non
      metastasizing malignancy. METHODS: Fischer 344 rats implanted with the
      methylcholanthrene-induced fibrosarcoma (MCA) were trained to meal-feed with
      access to food from 8:00 PM to 8:00 AM and water ad libitum. On day 13, rats were
      randomly divided into 3 study groups: (1) 5.0 g/kg per day EPA plus 10 IU vitamin
      E/g fat, (2) 5.0 g/kg per day corn oil plus 10 IU vitamin E/g fat, and (3) 5.0
      g/kg per day saline plus 10 IU vitamin E/g saline. The treatment was delivered
      via oral gavage twice daily. The animals were killed on day 29, and serum plus
      tissues (ie, liver and lung) were collected and frozen for analysis. Parameters
      evaluated include the following: tumor volume, weight loss, liver weight, total
      liver protein, liver lipid content, serum albumin content, and macrophage
      inflammatory protein-2 (MIP-2) levels. RESULTS: EPA-treated rats showed a
      reduction in tumor volume compared with corn oil (25% reduction, p < .01) and
      saline (33% reduction, p < .01) animals. EPA rats also demonstrated increased
      liver weight (p < .01) and total liver protein levels (p < .03) over saline
      treated animals. EPA- and corn oil-treated rats received more calories than the
      saline group because of the dietary fat treatments (p < .01) and had elevated
      lipid content in their livers (p = .05 and p = .04, respectively) compared with
      saline rats. Serum albumin (a marker of liver function) and MIP-2 levels (a
      marker of the hepatic acute phase response) were not different between treatment
      groups. CONCLUSIONS: EPA supplementation resulted in a dramatic reduction of
      tumor volume and mild improvements in weight maintenance. In addition, EPA
      treated animals demonstrated increased total liver protein and serum protein
      levels. Regression analyses showed that the weight and protein differences
      between treatment groups were not correlated with individual tumor volumes. The
      increase in liver and serum protein was not explained by differences in albumin
      or MIP-2. We conclude that the tumor growth inhibitory effects and
      anticachexiogenic effects of EPA are independent phenomena, and the effects on
      cachexia may be related to increased levels of undefined protein(s) in the liver
      and serum. To our knowledge, this is the first study to demonstrate the effects
      of EPA in the MCA fibrosarcoma model and is also novel in its evaluation of EPA
      as an anticachexiogenic therapy in progressive non-metastasizing malignancy.
      Further studies may identify the protein(s) elevated in the liver and the
      mechanisms for the development of EPA nutritional therapies for the treatment of
      progressive malignancies.

PMID- 12216710
TI  - Efficacy and tolerance of gastrostomy feeding in pediatric forms of neuromuscular
      diseases.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a simple and reliable
      method, but there are few data about its use in pediatric forms of neuromuscular
      diseases (NMD). The aim of this study was to evaluate the nutritional effects and
      tolerance of gastrostomy feeding in NMD patients. METHODS: Twelve patients with
      NMD, ranging in age from 1 month to 25.5 years, underwent a gastrostomy placement
      (PEG, n = 11; surgical gastrostomy, n = 1) between January 1990 and December
      2000. Diseases were muscular dystrophies (n = 5), infantile spinal muscular
      atrophies (n = 3), congenital myopathies (n = 3), and polyradiculoneuritis (n =
      1). Height-for-age (Z(H/A)), weight-for-age (Z(W/A)), and weight-for-height
      (Z(W/H)) z scores were assessed at birth, at the time of gastrostomy placement,
      after a 6-month and 1-year follow-up, and at the end of follow-up. Complications
      that occurred during the gastrostomy feeding period were recorded. Comparisons of
      z scores at the different times were performed with repeated-measures analyses of
      variance. RESULTS: Z(W/A) (p < .05) and Z(W/H) (p < .001) improved in the whole
      group after gastrostomy. For the 10 patients for whom follow-up was more than 1
      year, Z(W/A) (p < .03) and Z(W/H) (p < .001) increased from the time of
      gastrostomy to the end of follow-up. Among 5 patients who had a gastroesophageal
      reflux diagnosed before gastrostomy placement, 3 had at least 1 episode of
      pneumonia and 2 died of respiratory distress caused by the worsening of NMD. No
      other major complication was encountered. CONCLUSIONS: Gastrostomy feeding is
      well tolerated and results in an improvement of nutritional indices in NMD
      patients. Special care should be taken in patients with preexisting
      gastroesophageal reflux.

PMID- 12216711
TI  - Kinetics of diethylhexyl-phthalate extraction From polyvinylchloride-infusion
      lines.
AB  - BACKGROUND: For infusion therapy, polyvinylchloride (PVC)-infusion lines are
      commonly used. In this study, we examined the temperature dependency and the
      dynamics of extraction in the time course of infusion. METHODS: PVC-infusion
      lines used on the newborn ICU were perfused with a typical 24-hour fat infusion.
      We collected the perfused solution and measured the concentration of DEHP. This
      procedure was carried out at 27 degrees C and 33 degrees C. In another
      experiment, we examined the extraction rate in the time course of a 24-hour
      infusion. The infusion was collected every 4 hours. RESULTS: We discovered that
      extraction of DEHP depends highly on the surrounding temperature. Whereas at 27
      degrees C, the extraction of DEHP was 422.78 microg/mL, the leaching reached
      540.78 microg/mL at 33 degrees C under otherwise identical conditions. This is
      important because the temperature on a newborn ICU is between 31 and 37 degrees C
      in an incubator. In the other experiment, we found out that the extraction rate
      rose from 25.44 microg/mL in the first 4 hours to 478.1 microg/mL after 24 hours.
      CONCLUSIONS: The result of this study is that the actual daily load of DEHP for a
      2-kg newborn is 30% higher than measured before. The rate of extraction is
      dependent on the time of contact between solution and tubing. If PVC-infusion
      systems are used, solutions should be as cold as possible, and infusion time
      should be as short as possible.

PMID- 12216714
TI  - Short bowel syndrome.

PMID- 12216712
TI  - Physical characteristics of total parenteral nutrition bags significantly affect
      the stability of vitamins C and B1: a controlled prospective study.
AB  - BACKGROUND: Vitamin degradation occurring during the storage of total parenteral
      nutrition (TPN) mixtures is significant and affects clinical outcome. This study
      aimed to assess the influence of the TPN bag material, the temperature, and the
      duration of storage on the stability of different vitamins. METHODS: Solutions of
      multivitamin and trace elements at recommended doses were injected into either an
      ethylvinyl acetate (EVA) bag or a multilayered (ML) bag filled with 2500 mL of an
      identical mixture of carbohydrates (1200 kcal), fat (950 kcal), and amino acids
      (380 kcal). The bags were then stored at 4 degrees C, 21 degrees C, or 40 degrees
      C. Concentrations of vitamins A, B1, C, and E were measured up to 72 hours after
      compounding, using high-pressure liquid chromatography. RESULTS: Ten percent to
      30% of vitamin C degradation occurred within the first minutes after TPN
      compounding. Vitamin C was more stable in ML bags (half-life: 68.6 hours at 4
      degrees C, 24.4 hours at 21 degrees C, and 6.8 hours at 40 degrees C) than in EVA
      bags (half-life: 7.2 hours at 4 degrees C, 3.2 hours at 21 degrees C, and 1.1
      hour at 40 degrees C). Moreover, appearance of dehydroascorbic acid in the TPN
      mixture did not compensate for vitamin C losses. Vitamin B1 was stable at 21
      degrees C, but a 43% loss occurred at 40 degrees C after 72-hour storage in EVA
      bags. The other vitamins were stable in the TPN mixture stored in both bags at
      any temperature and without daylight protection. CONCLUSIONS: Degradations of
      vitamins C and B, are significantly reduced in ML bags compared with EVA bags. To
      prevent vitamin C deficiencies, its initial dose should be adapted to its
      degradation rate, which depends on the TPN bag material, the ambient temperature,
      and the length of time between TPN compounding and the end of infusion to the
      patient.

PMID- 12216716
TI  - Recognition, prevention, and treatment of home total parenteral nutrition central
      venous access complications.
AB  - Placement of central venous catheters for long-term administration of i.v.
      solutions in the home is associated with potential immediate and long-term
      complications. These complications can seriously threaten a patient's well-being
      and greatly increase costs. An understanding of anatomy and careful attention to
      detail can minimize the immediate complications, whereas thorough patient
      education and strict aseptic care techniques can reduce long-term complications.
      Early recognition and treatment of complications when they do occur can reduce
      patient injury and costs. In this document, the incidence, recognition,
      prevention, and treatment of various immediate and long-term complications will
      be discussed.

PMID- 12216715
TI  - Obtaining and maintaining vascular access in the home parenteral nutrition
      patient.
AB  - Obtaining and maintaining vascular access is a critical part of successful home
      parenteral nutrition (HPN) management. Most of the HPN related rehospitalization
      of patients is caused by problems associated with long-term vascular access. The
      causes of death in HPN patients are mostly related to their primary underlying
      disease. However, approximately 12% of deaths in HPN patients are related to
      catheter-associated problems. The appropriate placement of long-term vascular
      access devices and their care and management should be familiar to all clinicians
      helping to manage these patients and will be discussed.

PMID- 12216717
TI  - Clinical manifestations of nutrient deficiency.
AB  - BACKGROUND: Clinical manifestations of nutrient deficiencies are often overlooked
      by practitioners caring for patients receiving home nutritional therapies.
      METHODS: Literature review was conducted placing priority on identifying
      practical history and physical examination elements that may represent clinical
      manifestations of nutrient deficiency. RESULTS: Summary tables are presented that
      highlight key history and physical examination elements. CONCLUSIONS: Appropriate
      care of the patient receiving home enteral or parenteral nutrition therapies
      requires routine surveillance of these elements.

PMID- 12216718
TI  - Guidelines and available products for parenteral vitamins and trace elements.

PMID- 12216719
TI  - Parenteral nutrition-associated metabolic bone disease.
AB  - The incidence of parenteral nutrition-associated metabolic bone disease is
      unknown. Initial reports from the early 1980s suggested that both osteoporosis
      and osteomalacia were quite common in patients who receive long-term parenteral
      nutrition. The findings described in these early surveys provide a snapshot into
      the many factors that contribute to the development of metabolic bone disease.
      More recent evidence suggests that bone loss may not be as great with the
      initiation of parenteral nutrition as once was thought, and that most of the
      metabolic bone disease that is noted may be related to the patient's underlying
      illness. Although this recent information is reassuring, it is of the utmost
      importance to provide parenteral nutrition that minimizes further bone loss and
      promotes the formation of new bone. This review will describe the general
      features of metabolic bone disease and the abnormalities noted with parenteral
      nutrition-associated metabolic bone disease, highlight the importance of
      preexisting illness and parenteral nutrition associated factors that contribute
      to the development of metabolic bone disease, and finally discuss an approach to
      avoid this debilitating complication of long-term parenteral nutrition.

PMID- 12216720
TI  - Home enteral nutrition.

PMID- 12216721
TI  - Total parenteral nutrition-associated liver disease.

PMID- 12216722
TI  - Organ transplantation for intestinal failure.

PMID- 12216723
TI  - Length of life and quality of life on home parenteral nutrition.

PMID- 12216724
TI  - Demographics of home parenteral nutrition.

PMID- 12216725
TI  - Nutritional support in cancer patients.
AB  - This article will summarize the current nutrition strategies in cancer patients.
      A review of relevant studies dealing with nutrition in cancer patients is
      presented. Basic recommendations for feeding patients with malignancy are
      suggested. Early nutrition evaluation, assessment, and support should be
      instituted in the appropriate clinical setting. Use of specialized nutrition
      support is not indicated in well-nourished cancer patients undergoing surgery,
      chemotherapy, or radiotherapy in whom adequate oral intake is anticipated.
      Severely malnourished patients need early nutrition support preoperatively.
      Postoperative nutrition support has to be initiated in a timely fashion depending
      on the disease process. An algorithm for decisions regarding administration of
      specialized nutrition support is proposed.

PMID- 12216726
TI  - An agenda for the clinical science and practice of home parenteral nutrition.

PMID- 12216727
TI  - Home enteral nutrition from the provider's perspective.

PMID- 12216729
TI  - Plasticizer contamination from vacuum system O-rings in a quadrupole ion trap
      mass spectrometer.
AB  - The outgassing of plasticizers from Buna-N and Viton o-rings under vacuum lead to
      undesired ion-molecule chemistry in an Electrospray Quadrupole Ion Trap Mass
      Spectrometer. In experiments with the helium bath gas pressure >1.2 mTorr, or
      whenever analyte ions were stored for >100 ms, extensive loss of analyte ions by
      proton transfer or adduction with o-ring plasticizers bis(2-ethylhexyl) phthalate
      and bis(2-ethylhexyl) adipate occurred. A temporary solution to this
      contamination problem was found to be overnight refluxing in hexane of all the o
      rings in the vacuum system. This procedure alleviated this plasticizer
      contamination for approximately 100 hours of operation. These results, and those
      that lead to identification of the contamination as plasticizers outgassing from
      o-rings are described.

PMID- 12216728
TI  - Evaluation of small mass spectrometer systems for permanent gas analysis.
AB  - This work is aimed at understanding the aspects of designing a miniature mass
      spectrometer (MS) system. Several types of small MS systems are evaluated and
      discussed, including linear quadrupole, quadrupole ion trap, time of flight, and
      sector. Analysis of hydrogen, helium, oxygen, and argon in a nitrogen background
      with the concentrations of the components of interest ranging from 0 to 5000
      parts per million (ppm). The performance of each system in terms of accuracy,
      precision, limits of detection, response time, recovery time, scan rate, size,
      and weight is assessed. The relative accuracies of the systems varied from <1% to
      approximately 40% with an average below 10%. Relative precisions varied from 1%
      to 20%, with an average below 5%. The detection limits had a large distribution,
      ranging from 0.2 to 170 ppm. The systems had a diverse response time ranging from
      4 to 210 s, as did the recovery time with a 6-to-210-s distribution. Most
      instruments had scan times near 1 s; however, one instrument exceeded 13 s.
      System weights varied from 9 to 52 kg and sizes ranged from 15 x 10(3) cm3 to 110
      x 10(3) cm3. A performance scale is set up to rank each system, and an overall
      performance score is given to each system.

PMID- 12216730
TI  - An atmospheric pressure ion lens that improves nebulizer assisted electrospray
      ion sources.
AB  - An atmospheric pressure ion lens improves the performance and ease of use of a
      nebulizer assisted electrospray (ion spray) ion source. The lens is comprised of
      an oblong-shaped stainless steel ring attached to an external high voltage power
      supply. The lens is located near the tip of the conductive sprayer, and is
      maintained at a potential less than that of the sprayer. The ion lens improves
      the shape of the equipotential lines in the vicinity of the sprayer tip. This
      lens gives approximately a 2-fold reduction in the signal RSD, a 2-fold increase
      in the ion signal, an increase in the number of multiply charged ions, and a much
      broader range of usable sprayer positions.

PMID- 12216731
TI  - Quantitative analysis of technical polymer mixtures by matrix assisted laser
      desorption/ionization time of flight mass spectrometry.
AB  - We report quantitative MALDI-TOF measurements for polydimethylsiloxane (PDMS) of
      two different molecular weights using the relative ratio of the signal
      intensities of integrated oligomer distributions for these two molecular weight
      distributions. By reporting the ratio of intensities of the integrals of two
      oligomer distributions, we assume that the ionization and desorption
      efficiencies, crystallization conditions and other factors affecting intensity
      are similar. Poly(methyl methacrylate) (PMMA-33,000) was mixed with PDMS samples
      to show whether the presence of another material might affect the desorption
      efficiency. Quantitative values for the number-average molecular weight (Mn),
      weight-average molecular weight (Mw) and polydispersities (D) were calculated
      using the oligomer distributions. The results show a linear relationship between
      the analyte concentrations and the signal intensities in the range from 1,000 Da
      to 10,000 Da, and the desorption efficiency of these two PDMS materials was the
      same even in the presence of PMMA.

PMID- 12216732
TI  - Qualitative assessment of monomer ratios in putative ionic terpolymer samples by
      electrospray ionization mass spectrometry with collision-induced dissociation.
AB  - Collision-induced dissociation in the source of an electrospray (ES) mass
      spectrometer was employed to characterize putative samples of the ionic
      terpolymer poly(styrene sulfonate-co-acrylic acid-co-2-acrylamido-2-methyl-1
      propanesulfonic acid). Qualitative and semi-quantitative information about the
      monomer content was quickly obtainable from ES spectra, and indicated that some
      samples contained little or none of one or two expected comonomers. For two
      representative samples, confirmatory nuclear magnetic resonance (NMR) data were
      acquired. The NMR experiments required sample clean-up (to remove additives) and
      long acquisition times (up to 720 min) for 13C NMR. Cleanup also improved the ES
      results, providing better agreement with the NMR data. However, qualitative and
      semi-quantitative information was obtainable by ES (but not by NMR) without the
      cleanup step. Full quantitation of monomer ratios would require suitable
      standards, but even without such standards the ES measurements provide a rapid
      (<1 min) means for differentiating these samples (e.g., for process or quality
      control).

PMID- 12216733
TI  - Comparison of local anesthetic-cyclodextrin non-covalent complexes using
      capillary electrophoresis and electrospray ionization mass spectrometry.
AB  - Non-covalent complexes between three derivitized cyclodextrins (CD's) and six
      local anesthetics were studied using capillary electrophoresis (CE) and
      electrospray ionization mass spectrometry (ESI-MS). The CE study was performed
      using the complete filling technique (CFT). A comparison between the migration
      data from CE and ESI-MS inclusion complex peak abundances was made representing
      the association between local anesthetics and CD's in the solution and the gas
      phase, respectively. The results from this study showed comparable behavior of
      the complexes in the CE and mass spectrometer, indicating similarity in the
      parameters controlling the stability of these complexes. Therefore, the formation
      of specific non-covalent complexes, as shown in this study, could be used to
      predict the behavior of a complexing agent with a substrate in the solution phase
      by observing data obtained from ESI-MS.

PMID- 12216734
TI  - Electrospray tandem mass spectrometry of mixed-sequence RNA/DNA oligonucleotides.
AB  - The fragmentation of electrospray-generated multiply deprotonated RNA and mixed
      sequence RNA/DNA pentanucleotides upon low-energy collision-induced dissociation
      (CID) in a hybrid quadrupole time-of-flight mass spectrometer was investigated.
      The goal of unambiguous sequence identification of mixed-sequence RNA/DNA
      oligonucleotides requires detailed understanding of the gas-phase dissociation of
      this class of compounds. The two major dissociation events, base loss and
      backbone fragmentation, are discussed and the unique fragmentation behavior of
      oligoribonucleotides is demonstrated. Backbone fragmentation of the all-RNA
      pentanucleotides is characterized by abundant c-ions and their complementary y
      ions as the major sequence-defining fragment ion series. In contrast to the
      dissociation of oligodeoxyribonucleotides, where backbone fragmentation is
      initiated by the loss of a nucleobase which subsequently leads to the formation
      of the w- and [a-base]-ions, backbone dissociation of oligoribonucleotides is
      essentially decoupled from base loss. The different behavior of RNA and DNA
      oligonucleotides is related to the presence of the 2'-hydroxyl substituent, which
      is the only structural alteration between the DNA and RNA pentanucleotides
      studied. CID of mixed-sequence RNA/DNA pentanucleotides results in a combination
      of the nucleotide-typical backbone fragmentation products, with abundant w
      fragment ions generated by cleavage of the phosphodiester backbone adjacent to
      the deoxy building blocks, whereas backbone cleavage adjacent to ribonucleotides
      induces the formation of c- and y-ions.

PMID- 12216735
TI  - On the specificity of cyclodextrin complexes detected by electrospray mass
      spectrometry.
AB  - Alpha-cyclodextrin complexes with linear alpha,omega-dicarboxylic acids were
      investigated by electrospray mass spectrometry. These hydrophobic complexes are
      known to have an equilibrium binding constant that increases with the diacid
      chain length. However, the electrospray mass spectrometry (ES-MS) spectra showed
      that the relative intensity of the complex did not vary significantly with chain
      length. This contradiction is caused by a contribution of nonspecific adducts to
      the signal of the complex in ES-MS. In order to estimate the contribution of
      nonspecific adducts to the total intensity of the complexes with alpha
      cyclodextrin, the comparison was made between alpha-cyclodextrin and
      maltohexaose, the latter being incapable of making inclusion complexes in
      solution. The signal observed for complexes between diacids and maltohexaose can
      only result from nonspecific electrostatic aggregation, and is found to be more
      favorable with the shorter diacids. This is also supported by MS/MS experiments.
      A procedure is described which allows estimation of the contribution of the
      nonspecific complex in the spectra of the complexes with alpha-cyclodextrin by
      using the relative intensity of the complex with maltohexaose. The contribution
      of the specific complex to the total signal intensity is found to increase with
      the diacid chain length, which is in agreement with solution behavior.

PMID- 12216736
TI  - Increased proteome coverage for quantitative peptide abundance measurements based
      upon high performance separations and DREAMS FTICR mass spectrometry.
AB  - A primary challenge in proteome measurements is to be able to detect, identify,
      and quantify the extremely complex mixtures of proteins. The relative abundances
      of interest span at least six orders of magnitude for mammalian proteomes, and
      this constitutes an intractable challenge for high throughput proteome studies.
      We have recently described a new approach, Dynamic Range Enhancement Applied to
      Mass Spectrometry (DREAMS), which is based upon the selective ejection of the
      most abundant species to expand the dynamic range of Fourier transform ion
      cyclotron resonanace (FTICR) measurements. The basis of our approach is on-the
      fly data-dependent selective ejection of highly abundant species, followed by
      prolonged accumulation of remaining low-abundance species in a quadrupole
      external to the FTICR ion trap. Here we report the initial implementation of this
      approach with high efficiency capillary reverse phase LC separations and high
      magnetic field electrospray ionization FTICR mass spectrometry for obtaining
      enhanced coverage in quantitative measurements for mammalian proteomes. We
      describe the analysis of a sample derived from a tryptic digest of proteins from
      mouse B16 cells cultured in both natural isotopic abundance and 15N-labeled
      media. The FTICR mass spectrometric analysis allows the assignment of peptide
      pairs (corresponding to the two distinctive versions of each peptide), and thus
      provides the basis for quantiative measurements when one of the two proteomes in
      the mixture is perturbed or altered in some fashion. We show that implementation
      of the DREAMS approach allows assignment of approximately 80% more peptide pairs,
      thus providing quantitative information for approximately 18,000 peptide pairs in
      a single analysis.

PMID- 12216737
TI  - Non-covalent calixarene-amino acid complexes formed by MALDI-MS.
AB  - Non-covalent inclusion complexes formed between amino acids and derivatized
      calix[6]arenes are observed in MALDI mass spectrometry. The methyl, ethyl, and
      propyl ester derivatives of calix[6]arene yielded amino acid complexes, while the
      smaller calix[4]arene analogs did not. Similarly the underivatized calix[6]arene
      and calix[4]arene did not produce complexes. Amino acid complexes were observed
      for nearly all 20 amino acids in time-of-flight (TOF) analysis. In Fourier
      transform mass spectrometry (FTMS) analysis, however, only the most basic amino
      acids arginine, histidine, and lysine formed stable adducts. The complexes were
      abundant under matrix-assisted laser desorption ionization (MALDI) conditions,
      which suggested favorable interactions between host and guest.

PMID- 12216738
TI  - The role of the laser pulse duration in infrared matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - The role of the laser pulse duration in matrix-assisted laser
      desorption/ionization mass spectrometry with infrared lasers (IR-MALDI-MS)
      emitting in the 3 microm wavelength range has been evaluated. Mass spectrometric
      performance and characteristics of the IR-MALDI process were examined by
      comparing a wavelength-tuneable mid-infrared optical parametric oscillator (OPO)
      laser of 6 ns pulse duration, tuned to wavelengths of 2.79 and 2.94 microm, with
      an Er:YAG laser (lambda = 2.94 microm) with two pulse durations of 100 and 185
      ns, and an Er:YSGG laser (lambda = 2.79 microm) with a pulse duration of 75 ns.
      Threshold fluences for the desorption of cytochrome C ions were determined as a
      function of the laser pulse duration for various common IR-MALDI matrices. For
      the majority of these matrices a reduction in threshold fluence by a factor of
      1.2-1.9 was found by going from the 75-100 ns long pulses of the Erbium lasers to
      the short 6 ns OPO pulse. Within the experimental accuracy threshold fluences
      were equal for the 100 and the 185 ns pulse duration of the Er:YAG laser. Some
      pronounced pulse duration effects related to the ion formation from a glycerol
      matrix were also observed. The effect of the laser pulse length on the duration
      of ion emission was furthermore investigated.

PMID- 12216739
TI  - The acidity of uracil and uracil analogs in the gas phase: four surprisingly
      acidic sites and biological implications.
AB  - The gas phase acidities of a series of uracil derivatives (1-methyluracil, 3
      methyluracil, 6-methyluracil, 5,6-dimethyluracil, and 1,3-dimethyluracil) have
      been bracketed to provide an understanding of the intrinsic reactivity of uracil.
      The experiments indicate that in the gas phase, uracil has four sites more acidic
      than water. Among the uracil analogs, the N1-H sites have deltaH(acid) values of
      331-333 kcal mol(-1); the acidity of the N3 sites fall between 347-352 kcal mol(
      1). The vinylic C6 in 1-methyluracil and 3-methyluracil brackets to 363 kcal mol(
      1), and 369 kcal mol(-1) in 1,3-dimethyluracil; the C5 of 1,3-dimethyluracil
      brackets to 384 kcal mol(-1). Calculations conducted at B3LYP/6-31+G* are in
      agreement with the experimental values. The bracketing of several of these sites
      involved utilization of an FTMS protocol to measure the less acidic site in a
      molecule that has more than one acidic site, establishing the generality of this
      method. In molecules with multiple acidic sites, only the two most acidic sites
      were bracketable, which is attributable to a kinetic effect. The measured
      acidities are in direct contrast to in solution, where the two most acidic sites
      of uracil (N1 and N3) are indifferentiable. The vinylic C6 site is also
      particularly acidic, compared to acrolein and pyridine. The biological
      implications of these results, particularly with respect to enzymes for which
      uracil is a substrate, are discussed.

PMID- 12216740
TI  - A new derivatization strategy for the analysis of phosphopeptides by precursor
      ion scanning in positive ion mode.
AB  - Although numerous strategies have been devised to analyze protein
      phosphorylation, an abundant intracellular protein modification, there is still a
      need for different methods for the analysis of this modification. A method to
      both detect and localize the phosphorylation within a protein/peptide is
      especially required. In this paper, a new strategy is described, which makes use
      of beta-elimination/Michael addition reactions to introduce a functional group at
      the original site of phosphorylation, which gives rise to a dimethylamine
      containing sulfenic acid derivative with a unique m/z value. This enables the
      detection of the phosphorylated species within peptide mixtures by sensitive and
      specific precursor ion scanning in positive ion mode. Working under acidic
      conditions in positive ion mode has the added advantage that subsequent normal
      peptide sequencing for the exact localization can be performed. No other peptide
      derived fragment ion is observed at the m/z value of the sulfenic acid derivative
      formed, thus specific precursor ion experiments can also be carried out on
      instruments with low fragment ion resolution and lends itself to LC-MS/MS
      approaches when skimmer fragmentation routines or triple quadrupole mass
      spectrometers are used.

PMID- 12216741
TI  - The commercialization of human stem cells: ethical and policy issues.
AB  - The first stage of the human embryonic stem (ES) cell research debate revolved
      around fundamental questions, such as whether the research should be done at all,
      what types of research may be done, who should do the research, and how the
      research should be funded. Now that some of these questions are being answered,
      we are beginning to see the next stage of the debate: the battle for property
      rights relating to human ES cells. The reason why property rights will be a key
      issue in this debate is simple and easy to understand: it costs a great deal of
      money to do this research, to develop new products, and to implement therapies;
      and private companies, researchers, and health professionals require returns on
      investments and reimbursements for goods and services. This paper considers
      arguments for and against property rights relating to ES cells defends the
      following points: (1) It should be legal to buy and sell ES cells and products.
      (2) It should be legal to patent ES cells, products, and related technologies.
      (3) It should not be legal to buy, sell, or patent human embryos. (4) Patents on
      ES cells, products, and related technologies should not be excessively broad. (5)
      Patents on ES cells, products, and related technologies should be granted only
      when applicants state definite, plausible uses for their inventions. (6) There
      should be a research exemption in ES cell patenting to allow academic scientists
      to conduct research in regenerative medicine. (7) It may be appropriate to take
      steps to prevent companies from using patents in ES cells, products, and related
      technologies only to block competitors. (8) As the field of regenerative medicine
      continues to develop, societies should revisit issues relating to property rights
      on a continuing basis in order to develop policies and develop regulations to
      maximize the social, medical, economic, and scientific benefits of ES cell
      research and product development.

PMID- 12216742
TI  - Persons and their bodies: how we should think about human embryos.
AB  - The status of human embryos is discussed particularly in the light of the claim
      by Fox, in Health Care Analysis 8 that it would be useful to think of them in
      terms of cyborg metaphors. It is argued that we should consider human embryos for
      what they are--partially formed human bodies--rather than for what they are like
      in some respects (and unlike in others)--cyborgs. However to settle the issue of
      the status of the embryo is not to answer the moral questions which arise
      concerning how embryos should be treated. Since persons rather than bodies have
      rights, embryos do not have rights. However, whether or not embryos have rights,
      people can have duties concerning them. Furthermore, the persons whose fully
      developed bodies embryos will, might (or might have) become can have rights.
      Contrary to what is often assumed, it is not merely persons who have (or have
      had) living, developed human bodies who have moral rights: so it is argued in
      this paper.

PMID- 12216743
TI  - Intentional parenthood: responsibilities in surrogate motherhood.
AB  - In recent years, a number of writers dealing with questions over parenthood that
      arise in the context of reproductive technologies and surrogate motherhood, have
      appealed to the notion of "intentional parenthood". Basing their argument on
      liberal values such as individual autonomy, the freedom to enter contracts, the
      right to privacy, and individual self-fulfilment, they argue that contractually
      stated intentions, rather than genetic or gestational relationships, should form
      the basis of parental rights. Against this I argue that parental rights do not
      derive from contractual agreements, but are based in their obligations towards
      the child. I then examine the nature of the obligations that the various parties
      have towards the child both pre- and postnatally.

PMID- 12216744
TI  - Health inequalities and why they matter.
AB  - Health inequalities are of concern both because studying them may help one learn
      how to improve health and because health inequalities may be unjust. This paper
      argues that attending to these reasons why health inequalities may be important
      undercuts the claims of researchers at the World Health Organization in favor of
      focusing on individual health variation rather than on social group health
      differences. Inequalities in individual health are of little interest unless one
      goes on to study how they are related to other factors.

PMID- 12216746
TI  - Health care resource allocation: complicating ethical factors at the macro
      allocation level.
AB  - It is generally assumed that allocation problems in a socialized health care
      system result from limited resources and too much demand. Attempts at solutions
      have therefore centered in increasing efficiency, using evidence-based decision
      making and on developing ways of balancing competing demands within the existing
      resource limitation. This article suggests that some of the difficulties in macro
      allocation decision-making may result from the use of conflicting ethical
      perspectives by decision-makers. It presents evidence from a preliminary Canadian
      study to this effect.

PMID- 12216745
TI  - Equity in health care from a communitarian standpoint.
AB  - Equity in health and health care is an important issue. It has been proposed that
      the pursuit of equity in health care is being hampered by the dominance of
      individualism in health care practices. This paper explores the way in which
      communitarian ideals and practices might lend themselves to the pursuit of
      equity. Communitarians acknowledge, respect and foster the bonds that unite and
      identify communities. The paper argues that, to achieve equity in health care,
      these bonds need to be recognised and harnessed rather than ignored. The notion
      of individual autonomy in the context of the community is examined. Alternative
      concepts of autonomy--social autonomy and community autonomy--are seen to be more
      respectful and nurturing of both the individual and the community. Moreover,
      these concepts appear desirable for the pursuit of health care equity goals. The
      paper concludes with some thoughts about how equity in Australia's health care
      system can reasonably progress within a communitarian vision. Disadvantaged
      communities are discussed throughout, in particular, Australian Aboriginal
      communities.

PMID- 12216747
TI  - Distributive justice and the introduction of generic medicines.
AB  - INTRODUCTION: All countries face the issue of choice in healthcare. Allocation of
      healthcare resources is clearly associated with the concept of distributive
      justice and to the existence of a right to healthcare. Nevertheless, there is
      still the question of whether this right should include all types of healthcare
      services or if it should be limited to selected types. It follows that choices
      must be made, priorities must be set and that efficiency of healthcare services
      should be maximum. OBJECTIVES AND METHODS: Distributive justice aims at ensuring
      that everyone has access to necessary care based on the substantive ethical
      principles of equity and solidarity. Resource allocation is paramount in public
      policy particularly with regards pharmacoeconomics. The objective of this study
      is to determine the leading issues regarding the marketing and trade of generic
      medicines analysing the reasons why there are huge disparities between European
      countries with regards generic drugs acceptance by practitioners. RESULTS AND
      CONCLUSION: Distributive justice aims at ensuring that everyone has access to
      reasonable care based on the ethical principles of equity and solidarity.
      However, universality implies always choice in access and efficiency in delivery.
      It follows that resource allocation is instrumental in public policy particularly
      with regards pharmacoeconomics. The acceptance of distributive justice as a new
      ethical paradigm for professional ethics implies that as long as the best
      interest of the patient is not at stake physicians should regard the use of
      generic drugs as a valid instrument to promote the efficiency of the system and
      therefore as a way to facilitate citizen's global access to healthcare.

PMID- 12216748
TI  - Contrast-enhanced transrectal ultrasonography of a novel canine prostate cancer
      model.
AB  - OBJECTIVE: This study evaluated the utility of a new animal model for prostate
      cancer imaging using a new ultrasonographic contrast agent (Sonazoid [NC100100];
      Amersham Health, Oslo, Norway), for prostate cancer detection. METHODS: Twenty
      four dogs had a canine transmissible venereal sarcoma cell line injected (50
      million cells/mL) directly into the prostate, producing a neoplasm in 15 to 40
      days. Transrectal ultrasonography was performed in power Doppler mode on 8 dogs
      (phase I) and in gray scale phase inversion harmonic imaging mode on 16 animals
      (including control animals without tumors; phase II). Evaluations were repeated
      after intravenous injections of the contrast agent (dose, 0.00625-0.20
      microL/kg). Histopathologic examination was performed after each study. For the
      phase II experiments, sensitivity, specificity, and accuracy were calculated.
      RESULTS: The contrast agent improved visualization of the prostate cancer
      vascularity and delineation of tumor size and shape in both power Doppler and
      phase inversion harmonic imaging modes. Canine transmissible venereal sarcoma
      tumors ranging from 3 x 5 to 40 x 50 mm were detected. The accuracy for detecting
      the number of prostate tumors increased (in phase II) from 67% to 87% with the
      addition of the contrast agent. Histopathologic examination confirmed the
      ultrasonographic findings and revealed typical canine transmissible venereal
      sarcoma cells infiltrating the prostate with moderate neovascularity.
      CONCLUSIONS: The novel canine tumor model was useful for evaluating
      ultrasonographic prostate imaging techniques. Improved detection of prostate
      tumors in dogs was possible with gray scale phase inversion harmonic imaging of
      the contrast agent. The accuracy of lesion detection increased from 67% to 87%.

PMID- 12216749
TI  - Hepatocellular carcinoma: therapeutic experience with percutaneous ethanol
      injection under real-time contrast-enhanced color Doppler sonography with the
      contrast agent Levovist.
AB  - OBJECTIVE: To describe our experience with percutaneous ethanol injection under
      real-time contrast-enhanced color Doppler sonography with Levovist (SH U 508A;
      Nihon Schering, Osaka, Japan) for hepatocellular carcinoma after transcatheter
      arterial infusion. METHODS: Twenty patients (17 men and 3 women; mean age, 58.4
      years) with 23 hepatocellular carcinoma nodules (mean +/- SD, 2.7 +/- 1.5 cm)
      underwent percutaneous ethanol injection under real-time contrast-enhanced color
      Doppler sonography 1 week after transcatheter arterial infusion. Therapeutic
      effects were assessed by contrast-enhanced computed tomography and posttreatment
      fine-needle biopsy. This study was performed on a prospective basis. RESULTS:
      After the transcatheter arterial infusion, contrast-enhanced color Doppler
      sonography showed intense intratumoral color signals in all 23 hepatocellular
      carcinomas. After the percutaneous ethanol injection, contrast-enhanced color
      Doppler sonography, fine-needle biopsy, and contrast-enhanced computed tomography
      showed no color signals, no viable tumor tissues, and no enhancement in any of
      the 23 hepatocellular carcinomas. Three to 5 (mean, 3.3) percutaneous ethanol
      injection sessions with a 5.2- to 15.6-mL (mean, 12.8-mL) total volume of ethanol
      per tumor were required for complete disappearance of color signals on contrast
      enhanced color Doppler sonography. CONCLUSIONS: Percutaneous ethanol injection
      under real-time contrast-enhanced color Doppler sonography has considerable
      efficacy in treating hepatocellular carcinoma.

PMID- 12216750
TI  - Sonography of diffuse liver disease.
AB  - Sonography is often the first imaging procedure performed in the evaluation of
      individuals with suspected liver disease. Evaluation for biliary dilatation is
      always performed, because bile duct obstruction can cause abnormal liver test
      results, raising the suspicion of liver disease. Ultrasound is a useful but
      imperfect tool in evaluating diffuse liver disease. We discuss the uses and
      limitations of sonography in evaluating parenchymal liver disease. Sonography can
      show hepatomegaly, fatty infiltration of the liver, and cirrhosis, all with good
      but imperfect sensitivity and specificity. Sonography is of limited usefulness in
      acute hepatitis. Increased parenchymal echogenicity is a reliable criterion for
      diagnosing fatty liver. Cirrhosis can be diagnosed in the correct clinical
      setting when the following are present: a nodular liver surface, decreased right
      lobe-caudate lobe ratio, and indirect evidence of portal hypertension (collateral
      vessels and splenomegaly). Ultrasound plays an important role in the imaging of
      conditions and procedures common in patients with diffuse liver disease.

PMID- 12216751
TI  - Sonographically guided biopsy and sonographic monitoring in the diagnosis and
      follow-up of 2 cases of sarcoidosis with hepatic nodules and inconclusive
      thoracic findings.
AB  - OBJECTIVE: To report 2 cases in which abdominal sonography played a useful role
      in diagnosing sarcoidosis with early nodular hepatosplenic manifestations.
      METHODS: In the first case, an asymptomatic woman with increased liver enzyme
      values underwent sonography, which showed multiple hypoechoic nodules in the
      liver and spleen. Computed tomography confirmed the hepatosplenic findings and
      showed micronodular infiltrates of both lung fields, without hilar and
      mediastinal lymphadenopathy. In the second case, in a woman with a cough,
      dyspnea, and increased liver enzyme levels, thoracic computed tomography showed
      right pleural effusion causing partial atelectasis of the lower and middle lobes
      and mediastinal lymphadenopathy. RESULTS: Sonography and computed tomography
      showed multiple nodules of the liver and spleen and retroperitoneal
      lymphadenopathy. In both cases, bronchoscopy, bronchial and bronchioloalveolar
      lavages, and transbronchial and mediastinal biopsies had negative results.
      Sonographically guided biopsy of the hepatic nodules was carried out and sarcoid
      granulomas were detected in the portal areas. After 3 months of steroid therapy,
      liver enzyme values nearly normalized, and sonography showed the disappearance of
      all abdominal lesions. The first patient underwent control computed tomography,
      which confirmed the regression of the disease; the second patient refused control
      computed tomography. CONCLUSIONS: Sarcoidosis can occur with atypical onset, and
      in selected cases sonography may play a useful role in its diagnosis and follow
      up.

PMID- 12216752
TI  - Perineal sonography in diagnosis of an ectopic ureteric opening into the urethra.
AB  - OBJECTIVE: To study the role of perineal sonography in the diagnosis of an
      ectopic ureteric opening into the urethra. METHODS: In this study, carried out
      over about 4 years, perineal sonography was done to look for a ureter opening
      ectopically into the urethra in patients for whom abdominal sonography showed the
      ureter descending below and beyond the urinary bladder. RESULTS: Perineal
      sonography was done on 11 patients because there was a suggestion of an ectopic
      ureteric opening shown on abdominal sonography. In all of them, an ectopic
      ureteric opening into the urethra was shown on perineal sonography. The
      collecting system was seen to be nonduplicated in 6 patients and duplicated in 4
      patients, and a triple ureter was present in 1 patient. CONCLUSIONS: Perineal
      sonography is a simple, quick, beneficial, and noninvasive technique that can be
      used as an extension of abdominal sonography to diagnose an ectopic ureteric
      opening into the urethra.

PMID- 12216753
TI  - Sonography of a human jackstone calculus.
AB  - Jackstone calculi are urinary tract stones that have a specific appearance
      resembling toy jacks. They are almost always composed of calcium oxalate
      dihydrate and may be found in the urinary bladder or rarely in the upper urinary
      tract. Their appearance on plain radiographs and computed tomography (CT) in
      human patients has been well described. They have also been imaged in several
      species of animals. However, our review of the English medical literature
      revealed no previous report in which a jackstone calculus had been identified on
      the sonographic examination of a human patient. We report a case in which a large
      jackstone calculus was incidentally detected during abdominal sonography in a 75
      year-old man.

PMID- 12216754
TI  - Multiple hypoechoic hepatic lesions in a patient with Gaucher disease.
AB  - The most common symptoms of Gaucher disease include hepatosplenomegaly and anemia
      and thrombocytopenia due to hypersplenism. We describe the case of a patient with
      Gaucher disease who had cachexia, massive hepatomegaly, and multiple focal
      hepatic lesions. The clinical and radiologic findings suggested malignancy. A
      biopsy specimen was taken from a hepatic lesion and revealed infiltration by
      Gaucher cells. We discuss our findings in light of the putative increased
      incidence of hematologic malignancies in patients with Gaucher disease.

PMID- 12216755
TI  - Sonographically guided biopsy of bone and soft tissue tumors.

PMID- 12216756
TI  - Ultrasonographic diagnosis of pelvic echinococcosis.

PMID- 12216757
TI  - The comet tail artifact in the diagnosis of pneumothorax.

PMID- 12216758
TI  - A test phantom for estimating changes in the effective frequency of an ultrasonic
      scanner.
AB  - OBJECTIVE: Ultrasonic frequency is an important performance feature of B-mode
      scanners. It is particularly relevant when comparing instruments from different
      manufacturers and reporting clinical results. We investigated a test phantom to
      independently measure an effective imaging frequency, including effects of depth
      dependent attenuation and frequency filtering during echo reception. METHODS: The
      approach capitalizes on variations of the frequency dependence of backscatter
      with scatterer size. A tissue-mimicking phantom containing 48-microm-diameter
      scatterers was constructed. Embedded at depths of 1, 3, 7, and 9 cm were sets of
      cylindrical inclusions, each containing tissue-mimicking material with a
      different scatterer size and number density. Computer simulations helped
      establish scatterer parameters for the cylinder bodies that resulted in image
      contrast versus the background that varied with frequency, with each cylinder
      transitioning from negative to positive contrast at a different frequency.
      Acoustic properties of the phantom were verified by a laboratory apparatus.
      Initial tests of the effectiveness of the phantom were done by imaging with
      several scanners using various frequency and imaging settings on transducers.
      RESULTS: Images were obtained with 2 clinical scanners in which modest changes in
      the image acquisition parameters were adjusted. Image contrast between test
      cylinders and background corresponded to operating frequency with a multihertz
      transducer. Changes in observable contrast consistent with a shift in operating
      frequency were not always accompanied by visual indicators that such changes in
      the scanning protocol had occurred. CONCLUSIONS: The test phantom performs as
      predicted by computer simulations and theoretical calculations of backscatter
      versus frequency. Contrast on images of the test phantom produced by clinical
      systems correlates with scanner frequency settings, showing feasibility. Relative
      shifts in effective frequency and operating bandwidth can be assessed from these
      contrast differences between settings with this test phantom.

PMID- 12216759
TI  - Design of quality assurance for sonographic prostate brachytherapy needle guides.
AB  - OBJECTIVE: Needles are guided to their proper anatomic locations in
      sonographically guided percutaneous prostate brachytherapy by a mechanical system
      (template). A quality assurance procedure has been designed to test this
      template's alignment with the needle position overlay grid displayed in the
      sonographic image. METHODS: A mechanical arrangement was designed to position the
      needles properly with respect to the prostate probe's transducer in a liquid
      filled test tank. Two liquids were tested: tap water and an ethylene glycol
      mixture with an acoustic velocity of 1540 m/s. Needle images with the superposed
      grid were analyzed for needle placement accuracy. RESULTS: The tap water produced
      misregistration of the needle images. The ethylene glycol mixture yielded images
      of vertical and horizontal needle positions accurate to 0.3 and 1 mm,
      respectively. Also, the importance of selecting the lowest possible equipment
      echo amplitude dynamic range in these tests was shown. CONCLUSIONS: This quality
      assurance test with the ethylene glycol mixture will permit accurate alignment of
      the brachytherapy needle position overlay grid for each separate transrectal
      probe used.

PMID- 12216760
TI  - Cerebral hemodynamic patterns with technetium Tc 99m exametazime single photon
      emission computed tomography and transcranial Doppler sonography: a validation
      study using visual stimulation.
AB  - OBJECTIVE: To assess whether a correlation between perfusion changes to visual
      stimulus on the bilateral occipital areas and blood flow velocity changes to
      visual stimulus in both posterior cerebral arteries is present. METHODS: Nine
      right-handed healthy subjects (4 women and 5 men; mean +/- SD age, 58.0 +/- 5.6
      years) were included in the study. Visual stimulation was performed in room light
      with the subject's eyes open and looking around versus eyes closed as the
      stimulus-off condition. The blood flow velocities were recorded using
      transcranial Doppler sonography, and the regional cerebral blood flow
      measurements were recorded with the use of technetium Tc 99m exametazime and a
      single photon emission computed tomographic gamma camera system. Individual
      reactivity was defined as a relative increase of blood flow velocity and
      perfusion, which were calculated as percentage changes of baseline values.
      RESULTS: Visual stimuli produced a marked increase of blood flow velocity in both
      posterior cerebral arteries (35.2 +/- 2.3 cm/s; P < .001) without a significant
      side-to-side difference in all subjects as well as a marked increase of perfusion
      on both occipital areas (24.9 +/- 4.8 cm/s; P < .01). Moreover, there was a
      positive correlation between blood flow velocity changes and perfusion changes on
      both sides (r = 0.833; P < .01). CONCLUSIONS: The use of bilateral simultaneous
      Doppler recordings by means of a flow velocity averaging algorithm to a specific
      stimulus allows quantitative assessment of blood flow responses, and simple
      visual stimuli can be applied for different disorders to assess the vasomotor
      regulation that may result in measurable abnormal cerebral flow regulation even
      when clinically stabilized.

PMID- 12216761
TI  - Three-dimensional gray scale volume rendering of the liver: preliminary clinical
      experience.
AB  - OBJECTIVE: To investigate the potential clinical usefulness of three-dimensional
      gray scale volume rendering in the liver. METHODS: Sixty-two patients were
      enrolled in the study and categorized into 2 groups: group I with ascites and
      group II without. Two types of volume-rendering modes, i.e., surface and
      transparent, were used to obtain the three-dimensional images. The data were
      reviewed to identify the differences between two- and three-dimensional images of
      the liver in each subject. RESULTS: In group I, three-dimensional sonography was
      superior to two-dimensional sonography in terms of surface features, edges,
      overall three-dimensional impression, image clarity, and structural
      relationships. However, it seemed that three-dimensional sonography in the
      surface mode was inferior to two-dimensional sonography in showing intrahepatic
      structures, because it had decreased resolution. In group II, three-dimensional
      sonography was superior to two-dimensional sonography with respect to the
      continuity of intrahepatic vessels, overall three-dimensional impression of the
      vessels, image clarity, and the relationship between lesions and neighboring
      vessels. However, the resolution of the lesions was decreased in 7 cases of
      hepatocellular carcinoma. CONCLUSIONS: Our experience suggests that three
      dimensional gray scale volume rendering of the liver provides more diagnostic
      information than two-dimensional sonography; however, further studies are needed
      to evaluate its clinical importance.

PMID- 12216762
TI  - Preoperative ultrasonographic assessment of the number and size of gallbladder
      stones: is it a useful predictor of asymptomatic choledochal lithiasis?
AB  - OBJECTIVE: To evaluate whether preoperative ultrasonographic assessment of the
      number and size of gallbladder stones can identify patients at increased risk of
      having asymptomatic common bile duct stones. METHODS: Ultrasonographic data for
      300 consecutive patients undergoing laparoscopic cholecystectomy were analyzed.
      Patients were divided into a group in which multiple small (< or = 5 mm) or
      multiple variably sized (both < or = 5 and > 5 mm) gallbladder stones were
      present ("positive" stones) and a group with multiple large (> 5 mm) or single
      gallbladder stones, considered "negative." The ultrasonographic description was
      compared with surgical findings; finally, the prevalence of asymptomatic common
      bile duct stones in the 2 groups was compared. RESULTS: Ultrasonographic
      classification of gallbladder stones was confirmed at surgery in 285 cases (95%).
      Asymptomatic common bile duct stones were diagnosed in 9.5% of patients with an
      ultrasonographic diagnosis of positive gallbladder stones and in only 2.3% of
      patients with a diagnosis of negative gallbladder stones (P < .05). CONCLUSIONS:
      Ultrasonography is able to accurately show gallbladder stones; the appearance of
      multiple small and variably sized gallbladder stones represent a risk factor for
      synchronous asymptomatic common bile duct stones.

PMID- 12216763
TI  - Is same-day sonography of the gallbladder feasible after intravenous urography or
      contrast-enhanced computed tomography?
AB  - OBJECTIVE: To determine whether same-day sonographic evaluation of the
      gallbladder is possible after the use of oral or intravenous iodinated contrast
      agents during intravenous urography or computed tomography. METHODS: One hundred
      fifty-three patients involved in this prospective study received low-osmolar or
      conventional contrast material. Each preparation contained 300 mg/mL iodine.
      Sixty-six patients received contrast agents intravenously, and 87 received them
      orally. Gallbladder volume was estimated sonographically, and the precontrast
      volume was used to calculate the volume after contraction at 30-minute intervals
      up to 2 hours after contrast agent administration. RESULTS: Gallbladder volume
      returned to precontrast values at 2 hours irrespective of the type of contrast
      agent or route of administration. The mean volume after contraction at 0.5 hour
      was 71% after intravenous contrast agent administration and 76% after oral
      contrast agent administration. Both changes were statistically significantly
      different from precontrast values (P < .01, null hypothesis) and were unaffected
      by the osmolarity of the contrast agent. CONCLUSIONS: Gallbladder volume was
      restored to precontrast values 2 hours after contrast agent administration. Thus
      any strategy involving simultaneous same-day sonographic or computed tomographic
      assessment of the gallbladder after contrast agent administration can be
      confidently undertaken after this period. This finding may have cost-saving
      implications.

PMID- 12216764
TI  - Contrast-enhanced sonography of small pancreatic mass lesions.
AB  - OBJECTIVE: To evaluate the usefulness of contrast-enhanced wideband harmonic gray
      scale sonography in assessing the vascularity of small pancreatic mass lesions.
      METHODS: Twenty-five patients with 25 pancreatic mass lesions (20 pancreatic
      carcinomas, 1 islet cell tumor, 1 malignant lymphoma, and 3 focal inflammatory
      pancreatic masses due to chronic pancreatitis) were examined. All patients held
      their breath for 20 to 50 seconds after injection of a contrast agent while the
      vascularity of the tumor was observed on contrast-enhanced wideband harmonic gray
      scale sonography (early phase). We then monitored the tumor enhancement 60 to 120
      seconds after the injection while the patients held their breath for a few
      seconds (delayed phase). RESULTS: All 20 (100%) of the pancreatic carcinomas
      showed no contrast enhancement in the early phase. Fifteen (75%) of the 20
      pancreatic carcinomas also showed no contrast enhancement in the delayed phase.
      The remaining 5 (25%) pancreatic carcinomas showed mild enhancement in the
      peripheral regions of the tumor in the delayed phase. The other pancreatic masses
      showed mild or pronounced enhancement throughout the entire lesions in both the
      early and delayed phases. CONCLUSIONS: Contrast-enhanced wideband harmonic gray
      scale sonography is a useful tool for differentiating pancreatic carcinomas from
      focal inflammatory pancreatic masses or hypervascular pancreatic tumors.

PMID- 12216765
TI  - Hypoechoic normal renal sinus and renal pelvis tumors: sonographic
      differentiation.
AB  - OBJECTIVE: To evaluate the sonographic findings of an unusually hypoechoic renal
      sinus that mimics a tumor in the renal pelvis or renal sinus. METHODS:
      Sonographic scans of 7 patients with an unusually hypoechoic portion in the renal
      sinus were reviewed retrospectively. Computed tomography, excretory urography, or
      both confirmed all sinuses as normal. Five consecutive cases of renal pelvis
      tumors, which were detected on sonography initially in same period, were also
      reviewed to determine the differences between the 2 conditions. All cases were
      transitional cell carcinomas of the renal calyces. The images were analyzed for
      location, shape, margin, presence of posterior sonic attenuation, and associated
      findings such as caliectasis. RESULTS: Sonographic findings noted in patients
      with hypoechoic normal renal sinuses were irregular and poorly defined margins (n
      = 7), a central and symmetric location in the renal sinus (n = 6), the presence
      of posterior sonic attenuation with nonvisualization of the posterior border of
      the lesion (n = 7), an unaffected peripheral hyperechoic renal sinus (n = 7), and
      traversing hilar vessels in the lesion on color Doppler sonography (n = 7). In
      contrast, renal pelvis tumors had a relatively well-defined margin (n = 4), an
      eccentric location in the renal sinus (n = 2), a partially or completely
      obliterated hyperechoic renal sinus (n = 2), a visible posterior margin (n = 5),
      no posterior shadowing (n = 5), vessel displacement by the mass on color Doppler
      sonography (n = 5), and associated caliectasis (n = 1). CONCLUSIONS: By being
      familiar with the sonographic characteristics of a hypoechoic renal sinus, it can
      be differentiated from renal pelvis tumors, and unnecessary diagnostic workups
      can be avoided.

PMID- 12216766
TI  - Some aspects of arsenic toxicity and carcinogenicity in living organism with
      special regard to its influence on cardiovascular system, blood and bone marrow.
AB  - This paper gathers data on the most current aspects of arsenic action, especially
      its influence on the cardiovascular system, blood and bone marrow. A potential
      carcinogenic mechanism of arsenic is also discussed. Arsenic is a potent toxicant
      that may exist in several valencies and in a number of inorganic and organic
      forms. Most cases of arsenic-induced toxicity in humans are due to exposure to
      inorganic arsenic, and there is an extensive database on the human health effects
      of common arsenic oxides and oxyacids. Exposure of humans living near hazardous
      waste sites may involve inhalation of arsenic dusts in the air, ingestion of
      arsenic in water, food or soil, or dermal contact with contaminated soil or
      water. The exposure to arsenic via the inhalation route is responsible for the
      increased risk of lung cancer, although respiratory irritation, nausea and skin
      effects may also occur. The oral route of exposure to arsenic predominates in the
      general population. The most common effects of arsenic ingestion are
      gastrointestinal irritation, peripheral neuropathy, vascular lesions, anemia,
      skin diseases, including skin cancer and other cancers of the internal organs
      like bladder, kidney, liver or lung. Relatively little information is available
      on the effects of direct dermal contact with inorganic arsenicals, but several
      studies indicate local irritation and dermatitis as the major ones.

PMID- 12216767
TI  - From risk-based health surveillance to health promotion: an evidence-based
      experience in a health care setting.
AB  - In the European countries the health surveillance may be provided as a part of
      the national health system intervention. In Italy, the legislative Decree
      (626/94) makes the health surveillance compulsory for all those workers who are
      exposed to occupational risks. The aim of this study was to describe the
      introduction of preventive and protective measures, according to the new
      regulations, in the teaching hospital of the University of Modena. The population
      examined in 2000 included 1523 workers. Specific health surveillance protocols
      were prepared on the grounds of the risk characteristics based on the scientific
      evidence and on the risk perception. The intervention was oriented towards health
      promotion. The subjects were classified into 10 groups according to the risk
      characteristics. The percentage of workers ranged from 4% to 42%, depending on
      the exposure-related health changes. Moreover, the study explored some of the
      health surveillance benefits: an improvement in worker's satisfaction, an
      improvement in relationship between stakeholders, an early detection of health
      changes and a sickness absence reduction after the influenza vaccination program.

PMID- 12216768
TI  - Policy requirements and performance indicators for good practice in workplace
      health: public health perspectives.
AB  - The author lists the main objectives, work areas and benefits of good practice in
      health, environment and social management in enterprises (GP HESME). History of
      this cross-sectoral and multidisciplinary approach to management of occupational,
      lifestyle, environmental and social health determinants is outlined. Health
      policy requirements and performance indicators are provided to facilitate GP
      HESME implementation at the enterprise and local levels. The role of local
      authorities and networking of enterprises, representing various sectors is
      highlighted.

PMID- 12216769
TI  - Setting national targets to improve occupational health.
AB  - This paper describes a national strategy to improve occupational health and a
      longitudinal view of a 15 year project undertaken in the UK, logging the key
      developments. The first results should become apparent in 2005. Progress will be
      reported.

PMID- 12216770
TI  - Networking between occupational health services, client enterprises and other
      experts: difficulties, supporting factors and benefits.
AB  - This study explores difficulties, supporting factors and benefits of networking
      to studied enterprises and other network partners (focus on OHS and client
      enterprises). The study also explores social capital as a resource produced in
      network relations, and trust as a core dimension of social capital, and trust as
      a binding element in networking. The study is a mixed methods research (both
      qualitative and quantitative research materials). The most important supporting
      factors were: committed and active focus person, teamwork skills, long
      relationships, familiarity, trust and two-way communication in co-operation,
      shared goals, norms and values, an equal cost and benefit ratio, and the high
      quality of services. The biggest problems were the lack of skills to operate in
      the network and difficulties in maintaining the network, weak communication, lack
      of confidence, inconvenient size or composition of the network, overlapping
      information, cliques, nodes and missing links. The benefits were versatile:
      knowledge and skills accumulate, the network multiplies resources, fluency of co
      operation, innovations, commitment and trust increase, good practices expand, and
      moreover, the quality, many-sidedness and appropriateness of operations improve.
      Networking is beneficial but demanding. There are many limitations. Networks are
      not equal for every network partner (inequality in cost and benefit ratio).
      Networks produce social capital for participants. Successful networking requires
      trust relations between network partners.

PMID- 12216771
TI  - How is "coverage" defined for occupational health services?
AB  - The proportion of workers receiving occupational health services (OHS), or OHS
      coverage, is considered an important indicator in the evaluation of the national
      OHS levels. Although the term "coverage" is used in some papers, the definition
      of the term appears to vary from author to author. Despite vague definitions of
      the term, the issue has not been much studied. It appears that this vagueness has
      not led to attempts to establish a clear definition of the term. This study, was
      undertaken to clarify the meaning of "coverage" when used in relation to OHS.
      Papers using "coverage" as an indicator of the OHS levels or discussing the issue
      were collected and analyzed. The first aspect examined concerned the definition
      of "coverage." Next, the denominator (the target population), and methods for
      estimating the numerator (the number of workers provided with OHS) were described
      according to this definition. Few papers dealing with OHS coverage provided an
      explicit definition: none of the papers stated clearly the OHS functions
      encompassed when considering coverage, using simply the term in the context. Nor
      was the worker category to be represented in the denominator discussed, e.g.
      employees only, or the entire working population. The method for estimating the
      numerator was generally undefined. This study makes it clear that the term
      "coverage" in relation to OHS is currently used without clear definition. To
      permit objective assessments of the national OHS levels, "coverage" must be
      defined in terms of three elements: OHS functions, the numerator and the
      denominator of the proportion representing the extent of OHS coverage.

PMID- 12216772
TI  - Occupational health care system and its effectiveness in Lithuania.
AB  - The Ministry of Labor and Social Affairs in collaboration with the Ministry of
      Health Care carries out the activities aimed at solving occupational health and
      safety problems in Lithuania. Occupational health care system in Lithuania
      consists of three levels: 1) primary occupational health centers in the industry;
      2) general practitioners taking care of employees' health; and 3) the State Labor
      Inspectorate. The second level includes regional occupational medicine centers
      that are located in the three major cities of Lithuania: Vilnius, Kaunas and
      Klaipeda. Hygiene investigations of workplaces and prophylaxis of occupational
      diseases are performed by regional Public Health Center Departments of
      Occupational Medicine. The third level is provided by the Lithuanian Center of
      Occupational Medicine in Vilnius and the State Commission of Medical and Social
      Examination. The complicated cases of occupational diseases are treated in
      specialized departments of the University clinics. The real situation of work
      safety is not good. About 600 cases of occupational diseases and over 2500
      accidents, including 60 fatal causalities are registered annually.

PMID- 12216773
TI  - Trends and development of occupational health services in Norway.
AB  - Occupational Health Services (OHS) in Norway cover approximately 1.2 million
      employees, equivalent to 60% of the total work force. They employ nurses (800),
      physicians (500), physiotherapists (360), safety engineers (400), psychologists
      (30) and others (400), a total of 2500 full time employmancy. The average cost of
      the OHS amounts to 150 euros per employee, a total cost of 180 million euros per
      year. In 1998, the OHS in Norway were evaluated. The evaluation, initiated by the
      Ministry, revealed that although 80% of the enterprises are fairly satisfied with
      their OHS, there is still much to be improved, in particular quality development
      and customer focus. By 2000 the National Practice Guidelines. ("Good OHS") were
      developed as a joint effort of the professional OHS associations, representatives
      from the social partners and the NIOH. These guidelines have been evaluated and
      well accepted by the OHS. Last year the Ministry of Labour appointed an advisory
      group of experts on OHS. The group was asked to examine: the "branch provision"
      on obligatory OHS and the availability of health resources; the legislation on
      OHS tasks; the quality improvement of OHS; and the OHS in small enterprises The
      report was ready in May 2001 stating that the OHS may be a useful contributor to
      the improvement of the health, environment and safety in enterprises and included
      the following recommendations: to establish the OHS for all within 10 years and
      to ratify relevant ILO convention; to develop a certification system for the OHS;
      to ensure financial public support of the OHS for the small enterprises; and to
      expand the OH hospital departments as important supportive agents for the OHS.
      The report will be a background document for the revision process of the Work
      Environment Act to be soon put into force.

PMID- 12216774
TI  - Quality assessment in occupational health services: a review.
AB  - Various understanding of occupational health services (OHS) roles, structures and
      functions in European counties depends mainly on the legal, financial and
      organizational issues, which influence the health of employees. The OHS aims and
      functions are often related to public health, and/or to the management of
      enterprises. In consequence, quality assessment (QA) of OHS is used in the
      management of enterprises and the implementation of health policy. The study was
      performed to delineate the methods and techniques used in OHS QA and to find the
      most useful ones, which might be applied in Polish occupational health services.
      The web pages, current literature, and international reports on OHS were
      reviewed. The OHS tasks, activities and methods for OHS QA are different in
      different European countries. Numerous voluntary methods are believed to be more
      effective, but their effectiveness is not as yet unequivocally proven. Quality
      assessment methods in Polish OHS are more similar to those used in clinical
      medicine. Good Practice in Health Environment and Safety Management in
      Enterprises (GP HESME) offers a new insight into in OHS QA.

PMID- 12216775
TI  - Certification and quality assurance in Dutch occupational health services.
AB  - Since 1994, each Dutch enterprise has to be affiliated to an independent
      occupational health service (OHS), recognized by the government. In addition,
      each enterprise has to be supported by this occupational health service in its
      activities for the improvement of working conditions, and in the guidance of
      employees absent from work. From 1994 to 1998, the government was carrying out
      the certification and recognition of occupational health services. Since 1998 the
      certification has been carried out by private certifying institutions, in general
      consultancy bureaus that also provide ISO certification. In the Netherlands, the
      supervision of the quality of occupational safety and health care is twofold.
      Firstly, the Labor Inspectorate is checking if the enterprises keep to the rules.
      For example, each enterprise should have a risk assessment report at its
      disposal. The latter should be approved by the OHS. If an enterprise does not
      meet these rules, a penalty may be imposed. In practice, this happens rather
      seldom. Secondly, each OHS unit should be recognized by the Ministry of Social
      Affairs and Employment. The recognition takes place if the private certifying
      institution has assessed that the OHS meet a large number of requirements laid
      down in the "Guideline for the Certification of Occupational Health Services".
      This Guideline consists of 50 conditions and about 200 verification points. The
      requirements deal with the internal organzation and the output. By order of the
      Dutch government the IVA, a Dutch institute for social research, has recently
      investigated if this certification leads to a sufficient guarantee for
      appropriate occupational safety and health care. By means of a large number of
      discussions and workshops, the IVA has investigated how OHS, employees,
      employers, insurance companies and others judge the quality management. In this
      study, the current method of certification turned out to produce insufficient
      incentives for quality improvement. None of the involved parties turned out to be
      satisfied with the current system. The fundamental problem of this certification
      system can be summarized as follows. The requirements prescribe a quality
      management system in conformity with ISO, but they also contain a lot of
      organization rules, much more than ISO. It is this degree of specification that,
      if practiced slavishly, leads to an output that is not able to satisfy the needs
      and demands of employers, employees and government. There are no rules with
      regard to this output, but only to the process, e.g. the way an advice has been
      brought about. In this paper, we show how the current certification system is
      working, how this system has been evaluated, and what criticisms have been
      uttered. We also indicate how we might achieve a real improvement of quality
      management in prescribing much less details about the OHS internal organization,
      and in demanding employers and employees to make clear agreements about the
      desired OHS output and to monitor carefully if the agreed output quality has been
      achieved.

PMID- 12216776
TI  - Towards an effective co-operation between companies and occupational safety and
      health services.
AB  - In the Dutch Working Conditions Act, every employer is required to organize
      preventive occupational safety and health services (OSH-Services). The OSH
      Services need to have a certification that can be compared with ISO-9000. This
      article is focused on the question: How can companies and OSH-Services co-operate
      more effectively to obtain a better OSH management system inside the companies?
      To answer this question, TNO has developed an approach to support organisations
      in the health care branch to obtain a better service from their OSH-Service. TNO
      has chosen to focus on supporting the companies, because of the recognition that
      the effectiveness of OSH-Services has been found in effects on their customers,
      the companies. As a result of the research project a stepwise approach with
      several tools was developed. After the development phase, parts of the approach
      and the tools were used in several other consultancy projects. Evaluative studies
      have not been performed yet. However, from the development activities and several
      consultancy projects some remarkable evaluative findings can be given. The
      approach can be useful for companies and OSH-Services to make their goals and
      expectations more explicit. The approach also helps to make the management of
      companies clear that their own behaviour is relevant to the achievement of their
      goals in occupational health and safety policy, in addition to the services
      provided by the OSH-Service and their professionals. The approach cannot fulfil
      the possible need for qualification of OSH professionals. However, the approach
      can make the OSH professionals clear in what way they have qualification needs.

PMID- 12216777
TI  - Developing a model for occupational health provision in primary care.
AB  - This is a report of a survey commissioned by Newcastle and North Tyne Health
      Authority. The aim of the project was to assess the occupational health needs of
      both GPs and their staff working in the General Practice in Newcastle and North
      Tyneside. The aim of the survey has been to obtain information about occupational
      health needs from general practitioners and their practice managers. The survey
      design has been a cross-sectional study using questionnaires and practice visits.
      The information obtained from the practice managers was validated by visits to
      selected practices. The visits also facilitated a qualitative assessment of
      occupational health arrangements, training needs and issues that might be
      important in determining an appropriate model for a primary care-based
      occupational health service. The results of the needs analysis have shown both
      general support for an occupational health service and priority areas for such a
      service. The challenge will be to develop a service that delivers targeted
      occupational health in a way that is acceptable to all members of staff working
      in general practice. The service should be seen as a developing service,
      initially focused to provide a dual role. There will be a core occupational
      health service for all staff, including GPs, and a specialist service designed to
      meet the specific identified needs. There will be an opportunity to include the
      service in an overarching occupational health service within the Tyne and Wear
      area.

PMID- 12216778
TI  - Health and safety economics: limitations of economic appraisal of occupational
      health services activities in Poland.
AB  - Methods of economic appraisal developed for evaluating activities in health care
      system may as well be successfully used for evaluating occupational health
      service activities. This involves the problem of resources management and cost
      containment not only at the company level, but also at different managerial and
      institutional levels. The decision makers have to know what resources are spent
      on occupational health, what is the effectiveness and efficiency of investing in
      employees health. The key issue of good understanding of the theory and practice
      of economic appraisal is a precise definition of costs, effectiveness and
      benefits. Another important area is the identification of information sources and
      barriers of economic appraisal. The results of the project carried out by the
      Nofer Institute of Occupational Medicine have provided evidence that defining
      costs, effectiveness and benefits of preventive activities need to be developed.
      It becomes even more clear after an analysis of existing limitations of economic
      appraisal in Polish enterprises.

PMID- 12216779
TI  - The appropriateness of the MMPI-2 K correction.
AB  - The extent to which the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) K
      scale serves as a suppressor variable that influences the validity of clinical
      scale scores was examined using 274 male and 425 female outpatients from a
      community mental health center and 105 male and 247 female clients from a
      university psychological clinic. Hierarchical regression analyses were performed
      with MMPI-2 K scale scores and clinical scale scores as predictors and therapist
      ratings as criteria. In most cases, the K scale did not act as a suppressor
      Optimal K weights were different from the traditional K corrections. In most
      instances, there were no significant differences between correlations of
      therapist ratings with K-corrected and uncorrected clinical scale scores. The
      results do not support the K scale as a suppressor variable in these settings,
      although additional research is needed in settings where higher levels of
      defensiveness are common.

PMID- 12216780
TI  - The Inventory of Altered Self-Capacities (IASC): a standardized measure of
      identity, affect regulation, and relationship disturbance.
AB  - This article describes the Inventory of Altered Self-Capacities (IASC), a 63-item
      standardized measure of disturbed functioning in relation to self and others. The
      seven scales of the IASC are Interpersonal Conflicts, Idealization
      Disillusionment, Abandonment Concerns, Identity Impairment, Susceptibility to
      Influence, Affect Dysregulation, and Tension Reduction Activities. The
      psychometric properties of the IASC were examined in general population,
      clinical, and university samples. The IASC was found to have internal
      consistency/reliability and validity in all three samples. Generally as
      predicted, IASC scales were associated with existing measures tapping borderline
      and antisocial personality features, depression, suicidality, substance abuse,
      somatization, and dysfunctional sexual behavior

PMID- 12216781
TI  - Measures of Criminal Attitudes and Associates (MCAA): development, factor
      structure, reliability, and validity.
AB  - Recent meta-analysis has demonstrated that attitudes and associates are among the
      best predictors of antisocial behavior. Despite this finding, there are few
      psychometrically developed and validated measures of criminal and antisocial
      attitudes and associates. This study reviews the theoretical and empirical
      development of the Measures of Criminal Attitudes and Associates (MCAA), which is
      composed of two parts. Part A is a quantified self-report measure of criminal
      friends. Part B contains four attitude scales: Violence, Entitlement, Antisocial
      Intent, and Associates. The MCAA showed reasonable reliability (internal
      consistency and temporal stability) and appropriate convergent and discriminant
      validity. Criterion validity was evidenced in the scale's relationship with
      criminal history variables, and a factor analysis confirmed the four distinct
      scale domains.

PMID- 12216782
TI  - Dyadic short forms of the Wechsler Adult Intelligence Scale-III.
AB  - Various short forms of the Wechsler Adult Intelligence Scale (WAIS)/WAIS-R have
      been developed to obtain estimates of overall intellectual level, although little
      research of WAIS-III short forms has been published to date. Full Scale IQ (FSIQ)
      estimatesfromfour WAIS-III dyadic short forms were obtained by entering selected
      subtest scores from a mixed neurologic/ psychiatric sample (n = 196) into
      regression equations. Results were cross validated on a second sample (n = 57).
      Within both samples, WAIS-III FSIQ scores were highly correlated (r = .90-.92, p
      < .001) with estimated FSIQ scores. Estimated FSIQ fell within 5 points of actual
      FSIQ in 49% to 74% of cross-validation cases and within 10 points of actual FSIQ
      in 81% to 93% of the sample. Comparable to findings from previous short-form
      investigations, actual and estimated FSIQ classification levels agreed in 46% to
      67% of cases in the cross-validation sample. These dyadic WAIS-III forms appear
      appropriate for obtaining gross estimates of FSIQ in similar populations,
      although caution is recommended in interpreting estimated IQ scores.

PMID- 12216783
TI  - Concurrent validity of the Personality Assessment Inventory Alcohol Problems
      (ALC) Scale in a college student sample.
AB  - The concurrent validity of the Alcohol Problems scale (ALC) was investigated in a
      college student sample (N = 200). The relationships between the ALC and
      associated features of alcohol problems (e.g., consumption patterns,
      expectancies, maladaptive coping, and stress) were examined. The validity of the
      ALC for identifying clinically significant alcohol problems (assessed with the
      Structured Clinical Interview for the fourth edition ofthe Diagnostic and
      Statistical Manual of Mental Disorders) was also examined. The ALC was related to
      the associated features and was a valid indicator of alcohol problems. T scores
      of 80, 85, and 90 had superior hit rates for alcohol abuse; and scores of 80, 85,
      and 90 had superior hit rates for alcohol dependence.

PMID- 12216784
TI  - Temporal stability of the Wisconsin Card Sorting Test in a chronic traumatic
      brain injury sample.
AB  - The aim of the present study was to investigate the temporal stability of the
      Wisconsin Card Sorting Test (WCST) in a clinical population with documented brain
      pathology, stable cognitive deficits, and for whom repeated testing is common:
      chronic severe traumatic brain injury (TBI). Participants were 34 patients at
      least 1 year post severe TBI living at a large residential rehabilitation
      facility. The WCST was administered in standard fashion with both the standard
      and 64-card versions scored. All derived scores with norms were examined. Results
      indicated acceptable temporal stability of most scores for both the standard and
      short WCST, although the stability of the WCST-64 was poorer than for the
      standard WCST. Three sets of significant change indices are provided for clinical
      use.

PMID- 12216785
TI  - The Psychological Inventory of Criminal Thinking Styles (PICTS): a review and
      meta-analysis.
AB  - The Psychological Inventory of Criminal Thinking Styles (PICTS) is an 80-item
      self-report measure designed to assess crime-supporting cognitive patterns. Data
      from men (N = 450) and women (N = 227) offenders indicate that the PICTS
      thinking, validity, and content scales possess moderate to moderately high
      internal consistency and test-retest stability. Meta-analyses of studies in which
      the PICTS has been administered reveal that besides correlating with measures of
      past criminality, several of the PICTS thinking and content scales are capable of
      predicting future adjustment/release outcome at a low but statistically
      significant level, and two scales (En, CUR) are sensitive to program-assisted
      change beyond what control subjects achieve spontaneously. The factor structure
      of the PICTS is then examined with the aid of exploratory and confirmatory factor
      analysis, the results of which denote the presence of two major and two minor
      factors.

PMID- 12216786
TI  - Hand-scoring error rates in psychological testing.
AB  - Despite the comprehensive treatment of test validity in most technical manuals,
      test authors appear to routinely assume that clients and professionals will score
      their instruments without error. Recently Allard and Faust challenged this
      assumption by suggesting that error rates "may not be rare or benign" and
      demonstrated that tests with more complex scoring procedures were associated with
      a greater number of scoring errors. This study investigated error rates that
      resulted from hand scoring seven psychometric tests commonly employed in
      psychological practice. Significant and serious error rates were identified for
      both psychologist and client scorers across all tests investigated. Scoring
      complexity was found to predict the base rate of scorer errors. The findings
      suggest that greater development in and attention to test-scoring procedures is
      required to restrict the likelihood of scorer error.

PMID- 12216787
TI  - Detecting malingered neurocognitive dysfunction using the reliable digit span in
      traumatic brain injury.
AB  - This study assessed the effectiveness of Greiffenstein's Reliable Digit Span
      (RDS) score for the detection of malingered neurocognitive dysfunction.
      Participants were 54 traumatic brain injury patients referred for
      neuropsychological evaluation. Twenty-four met the Slick, Sherman, and Iverson
      criteria for at least probable malingered neurocognitive dysfunction. The control
      group was composed of 30 patients without external incentive and who thus did not
      meet the Slick criteria. All patients completed the digit span test as part of
      either the WAIS-R or WAIS-III. The RDS scores were calculated, and sensitivity,
      specificity, and predictive power were examined for several cutoffs.
      Classification accuracy for the RDS was excellent. Issues related to the clinical
      application of this technique are discussed.

PMID- 12216788
TI  - Producing progeny from endangered birds of prey: treatment of urine-contaminated
      semen and a novel intramagnal insemination approach.
AB  - Wild raptors brought into an ex situ environment often have poor semen quality
      that is further compromised by urine contamination. Generally, it is believed
      that in birds, artificial insemination into the cloaca or caudal vagina of
      females requires large doses of high-quality spermatozoa to maximize fertility.
      In an effort to define and overcome some of the challenges associated with
      reproduction in wild raptors, the objectives of this study were to 1) evaluate
      the frequency, impact, and remediation of urine contamination in fresh ejaculates
      for the purpose of maintaining sperm motility and viability in vitro, and 2)
      develop a deep insemination method that allows low numbers of washed sperm to be
      placed directly into the magnum to increase the probability of producing
      fertilized eggs. The species evaluated include golden eagle (Aquila chrysoetos),
      imperial eagle (A. adalberti), Bonelli's eagle (Hiernaetus fasciatus), and
      peregrine falcon (Falco peregrinus). Semen samples were collected and pooled by
      species, and a minimum of 25 pooled ejaculates per species were evaluated for
      urine contamination, pH, sperm viability, and sperm motility; the samples were
      either unwashed or washed in neutral (pH 7.0) or alkaline (pH 8.0) modified
      Lake's diluent. Female golden eagles and peregrine falcons were inseminated via
      transjunctional, intramagnal insemination with washed spermatozoa from urine
      contaminated samples. Urine contamination occurred in 36.8 +/- 12.8% (mean +/-
      SEM) golden eagle, 43.1 +/- 9.1% imperial eagle. 28.7 +/- 16.1% Bonelli's eagle,
      and 48.2 +/- 17.3% peregrine falcon ejaculates. The pH in urine-contaminated
      semen samples ranged from 6.48 +/- 0.3 to 6.86 +/- 0.2, and in noncontaminated
      samples it ranged from from 7.17 +/- 0.1 to 7.56 +/- 0.1. Sperm viability and
      motility were reduced (P < 0.05) in all species for unwashed vs. washed sperm
      after 30 min incubation at room temperature. Two peregrine falcon chicks and one
      golden eagle chick hatched after intramagnal insemination. This study
      demonstrates that urine contamination, a common and lethal acidifier in manually
      collected raptor ejaculates, can be circumvented by immediate, gentle seminal
      washing. Furthermore, these processed sperm, when deposited by transjunctional
      intramagnal insemination, can produce live young.

PMID- 12216789
TI  - Diet composition and blood values of captive cheetahs (Acinonyx jubatus) fed
      either supplemented meat or commercial food preparations.
AB  - Nutrition most certainly affects health and may play a role in the etiology of
      growth and reproductive problems in captive cheetah (Acinonyxjubatus)
      populations. The objective of our research was to examine nutritional differences
      between two dietary regimens and quantify their physiologic effects on cheetahs
      held in captivity. Twelve cheetahs were randomly assigned to either a commercial
      diet (COM) or a supplemented meat diet (SMD) group. These cats were physically
      examined and had blood samples taken three times over the course of a year.
      Representative samples of COM and four separate components of the SMD treatment
      were analyzed over the same time frame for proximate nutrient composition,
      digestibility, and concentrations of taurine, fat-soluble vitamins, and selected
      minerals. Concentrations of fat, vitamins A and E, Se, Fe, Cu, Na, and Mn were
      significantly higher in COM compared with those in SMD samples, with the
      exception of fat content in turkey. Mg content was lower in COM than in SMD;
      other nutrients did not differ. Mean concentrations of vitamins A and E in COM
      were markedly higher than in SMD samples (408,140 vs. 29,696 IU/kg dry matter
      [DM] and 431 vs. 48 IU/kg DM, respectively) and varied dramatically between
      sampling periods. Percent crude protein and protein-to-fat ratios were high for
      SMD compared with either whole prey-based or commercial food preparations. Blood
      urea nitrogen and serum creatinine levels were above normal reference means for
      domestic cats. Plasma concentrations of vitamins A, D, and E were significantly
      higher in COM-fed than in SMD-fed cheetahs. Both plasma retinol and tocopherol
      levels were almost three times higher in COM-fed cats (1.26 +/- 0.06 vs. 0.53 +/-
      0.03 microg/ml and 17.5 +/- 0.7 vs. 6.4 +/- 0.02 microg/ml, respectively) and
      exceeded the normal ranges expected for domestic felids. Significant differences
      between male and female cheetahs were found for plasma concentrations of vitamin
      E, Se, and Fe after allowing for effects of diet and time of collection. Excess
      fat-soluble dietary vitamins can result in direct toxicities as well as nutrient
      antagonisms and may be linked to reproductive and health issues in captive
      cheetahs. The high protein levels found in SMD may be linked to chronic renal
      disease, which was detected in some of these cheetahs.

PMID- 12216790
TI  - Pharmacokinetics of fluconazole in loggerhead sea turtles (Caretta caretta) after
      single intravenous and subcutaneous injections, and multiple subcutaneous
      injections.
AB  - Superficial and systemic mycotic infections are common among clinically ill sea
      turtles, which places growing importance on the establishment of pharmacokinetic
      based dosage regimens for antifungal drugs. The pharmacokinetic properties of the
      antifungal drug fluconazole, after intravenous (i.v.) and subcutaneous (s.c.)
      injections, were studied in juvenile loggerhead sea turtles (Caretta caretta)
      housed at 23.0-26.5 degrees C. Fluconazole pharmacokinetic properties were
      further assessed in a multiple-dose s.c. regimen derived from the pharmacokinetic
      parameters determined in the single-dose study. Pharmacokinetic parameters were
      calculated, using a two-compartment model, from plasma concentration-time data
      obtained after single i.v. and s.c. administrations of fluconazole at a dosage of
      2.5 mg/ kg body weight in six juvenile sea turtles. Blood samples were collected
      at intervals through 120 hr after each dose, and the concentration of fluconazole
      in plasma was measured by reverse-phase high-performance liquid chromatography.
      The i.v. and s.c. elimination half-lives were 139.5 +/- 36.0 and 132.6 +/- 48.7
      hr (mean +/- SD), respectively. Systemic clearance of fluconazole was 8.2 +/- 4.3
      ml/kg x hr, and the apparent volume of distribution at steady state was 1.38 +/-
      0.29 L/kg. A multiple-dose regimen was derived, which consisted of a loading dose
      of 21 mg/kg body weight and subsequent doses of 10 mg/kg administered through
      s.c. injection every 120 hr (5 days). This regimen was administered to four
      juvenile sea turtles for 10 days, and blood samples were taken to determine peak
      and trough plasma concentrations of fluconazole. The mean concentrations for the
      two peak concentrations were 16.9 +/- 1.1 and 19.1 +/- 2.8 microg/ml 4 hr after
      dosing, and the mean concentrations for the three trough concentrations were 7.2
      +/- 2.2, 10.4 +/- 2.7, and 10.7 +/- 2.9 microg/ml 120 hr after dosing. The
      terminal half-life after the last dose was calculated at 143 hr. Throughout the
      multiple dosing, fluconazole concentrations remained above approximately 8
      microg/ml, a concentration targeted when treating mycotic infections in humans.
      The results of this study suggest that fluconazole can be effectively
      administered to sea turtles at a dosage of 10 mg/kg every 5 days after a loading
      dose of 21 mg/kg.

PMID- 12216791
TI  - Evaluation of medetomidine-ketamine anesthesia with atipamezole reversal in
      American alligators (Alligator mississippiensis).
AB  - Sixteen captive and wild-caught American alligators (Alligator mississippiensis),
      seven juveniles (< or = 1 m total length [TL]; 6.75 +/- 1.02 kg), and nine adults
      (> or = 2 m TL; 36.65 +/- 38.85 kg), were successfully anesthetized multiple
      times (n = 33) with an intramuscular (i.m.) medetomidine-ketamine (MK)
      combination administered in either the triceps or masseter muscle. The juvenile
      animals required significantly larger doses of medetomidine (x = 220.1 +/- 76.9
      microg/kg i.m.) and atipamezole (x = 1,188.5 -/+ 328.1 microg/kg i.m.) compared
      with the adults (medetomidine, x = 131.1 +/- 19.5 microg/kg i.m.; atipamezole, x
      = 694.0 +/- 101.0 microg/kg i.m.). Juvenile alligators also required higher
      (statistically insignificant) doses of ketamine (x = 10.0 +/- 4.9 mg/kg i.m.)
      compared with the adult animals (x = 7.5 +/- 4.2 mg/kg i.m.). The differences in
      anesthesia induction times (juveniles, x = 19.6 +/- 8.5 min; adults, x = 26.6 +/-
      17.4 min) and recovery times (juveniles, x = 35.4 +/- 22.1 min; adults, x = 37.9
      +/- 20.2 min) were also not statistically significant. Anesthesia depth was
      judged by the loss of the righting, biting, corneal and blink, and front or rear
      toe-pinch withdrawal reflexes. Recovery in the animals was measured by the return
      of reflexes, open-mouthed hissing, and attempts to high-walk to the opposite end
      of the pen. Baseline heart rates (HRs) were significantly higher in the juvenile
      animals (x = 37 +/- 4 beats/min) compared with the adults (x = 24 +/- 5 bpm).
      However, RRs (juveniles, x = 8 +/- 2 breaths/min; adults, x = 8 +/- 2
      breaths/min) and body temperatures (juveniles, x = 24.1 +/- 1.1 degrees C;
      adults, x = 25.2 +/- 1.2 degrees C) did not differ between the age groups. In
      both groups, significant HR decreases were recorded within 30-60 min after MK
      administration. Cardiac arrhythmias (second degree atrio-ventricular block and
      premature ventricular contractions) were seen in two animals but were not
      considered life-threatening. Total anesthesia times ranged from 61-250 min after
      i.m. injection. Although dosages were significantly different between the age
      groups, MK and atipamezole provided safe, effective, completely reversible
      anesthesia in alligators. Drug-dosage differences appear to be related to
      metabolic differences between the two size-classes, requiring more research into
      metabolic scaling as a method of calculating anesthetic dosages.

PMID- 12216792
TI  - Chemical restraint of fishers (Martes pennanti) with ketamine and medetomidine
      ketamine.
AB  - We chemically restrained fishers (Martes pennanti) as part of a captive
      management protocol designed to facilitate veterinary evaluation and treatment,
      and conditioning on a high-calorie diet before reintroduction in Pennsylvania. We
      compared the safety and efficacy of ketamine (KET) and medetomidine-ketamine (MED
      KET) by monitoring immobilization intervals (induction time, down time, alert
      time, and recovery time) and physiologic responses (pulse rate, respiration rate,
      rectal temperature, blood pressure, oxygen saturation, and mean arterial
      pressure) during restraint. We administered MED-KET at 0.4 mg MED combined with
      20.0 mg KET to males and at 0.2 mg MED combined with 10.0 mg KET to females. The
      x +/- SD dosages were MED 0.07 +/- 0.008 mg/kg + KET 3.7 +/- 0.5 mg/ kg for males
      and MED 0.07 +/- 0.007 mg/kg + KET 3.6 +/- 0.3 mg/kg for females. KET alone was
      administered at 100.0 mg to males and at 50.0 mg to females. resulting in x +/-
      SD dosages of 18.7 +/- 1.8 mg/kg for males and 19.2 +/- 2.2 mg/kg for females.
      Mean induction time did not differ between fishers restrained with MED-KET (4.6
      min) and KET (4.5 min). However, compared with KET, MED-KET resulted in longer
      mean down time (36.2 vs. 142.2 min), alert time (40.8 vs. 146.8). and recovery
      time (81.1 vs. 199.4 min). Fishers that received MED-KET were mildly bradycardic
      and hypertensive compared with those that received KET. Although KET resulted in
      increased muscle tension and labored respiration, it would be effective for
      performing brief, noninvasive procedures for fishers because induction was rapid,
      recovery was short and calm, anesthesia was not profound, and physiologic
      response was generally expected on the basis of known drug pharmacology.
      Medetomidine-ketamine also immobilized fishers effectively, providing rapid
      induction, physiologic response typical to alpha2 agonism, calm recovery, and
      possibly a plane of anesthesia adequate for invasive procedures such as tooth
      removal or surgery.

PMID- 12216793
TI  - Evaluation of safety and efficacy of acaricides for control of the African
      tortoise tick (Amblyomma marmoreum) on leopard tortoises (Geochelone pardalis).
AB  - Nine acaricides (amitraz, carbaryl, chlorpyrifos, cyfluthrin, fipronil, lindane,
      permethrin, phenothrin, and pyrethrins) were studied for their efficacy in
      killing the African tortoise tick (Amblyomma marmoreum). Only four of the
      acaricides (chlorpyrifos, cyfluthrin, lindane, and permethrin) produced 100%
      mortality within 24 hr of application, and only two (cyfluthrin and permethrin)
      continued to cause 100% mortality when diluted to as low as 1:10,000. Five of the
      acaricides (amitraz, carbaryl, chlorpyrifos, cyfluthrin, and permethrin) were
      studied for toxicity to the leopard tortoise (Geochelone pardalis), the most
      common host of A. marmoreum. The results indicate that cyfluthrin and permethrin,
      which were herein found to be the two most effective acaricides for control of A.
      marmoreum, are also the safest acaricides for use on leopard tortoises.

PMID- 12216794
TI  - Intraocular pressure determination in clinically normal red-footed tortoise
      (Geochelone carbonaria).
AB  - Intraocular pressure (IOP) reflects a balance between aqueous humor production
      and outflow and is often an essential ophthalmic diagnostic procedure in animals.
      The objective of this study was to estimate IOP in clinically normal red-footed
      tortoises (Geochelone carbonaria) of various sizes by using applanation
      tonometry. Intraocular pressures were estimated for 25 captive red-footed
      tortoises (10 males, 10 females, and 5 animals of unknown sex) by using an
      applanation tonometer after topical anesthesia. Body length ranged from 5.1 to
      54.9 cm, measured from nuchal to anal scutes. Five measurements from each eye
      were obtained by a single observer in an ambient temperature of approximately 30
      degrees C. Observer's reliability was good (intraclass r = 0.75), and IOP did not
      change over the ordered sequence of five replicate measurements. For individual
      tortoises the correlation for IOP between the left and right eyes was low (r =
      0.20). The paired t-test did not show any statistical effect (P = 0.426) for the
      difference in IOP between the left and right eyes. Mean IOP determined for 10
      confirmed males and 10 confirmed females did not differ between sexes (P =
      0.244). The mean IOP of five small tortoises (< 10 cm long) was not significantly
      different (P = 0.244) from that of 20 large tortoises (> 10 cm long). In red
      footed tortoises there does not appear to be any relation between carapace length
      and IOP.

PMID- 12216795
TI  - First report of a parasitic copepod (Pennella balaenopterae) infestation in a
      pinniped.
AB  - An infestation by the parasitic copepod Pennella balaenopterae was found in a
      stranded, 8-mo-old, female northern elephant seal (Mirounga angustirostris).
      Diagnosis was based on the finding of the cephalothoraxes of 14 adult female
      copepods from three subcutaneous sites. Bacteria cultured from lesion exudate
      included Arcanobacterium phocae, Escherichia coli, Edwardsiella tarda, an
      Enterococcus sp., and Proteus mirabilis. The lesions were drained and irrigated
      with chlorhexidine, and the seal was treated with a subcutaneous injection of
      ivermectin. The seal recovered and was released after 43 days.

PMID- 12216797
TI  - Adenoviral infection in captive moose (Alces alces) in Canada.
AB  - Adenoviral infection was associated with hemorrhagic enteritis, serosal
      hemorrhages, and severe pulmonary edema in six captive moose (Alces alces) in
      Toronto, Ontario, Canada: an adult female moose and three calves in 1985 and two
      calves in 1998. Adenoviral disease was suspected based on histological findings
      of systemic vasculitis and widespread thrombosis associated with amphophilic
      intranuclear inclusions in endothelial cells. Diagnosis was confirmed by
      immunohistochemistry using antiserum to bovine adenovirus type 5, transmission
      electron microscopic identification of viral particles consistent in morphology
      with adenovirus within nuclei of pulmonary endothelial cells in an affected calf,
      and virus isolation. The restriction pattern of virus isolated from the lung of
      one of the calves indicated that the virus was identical to a recently
      characterized adenovirus in black-tailed deer (Odocoileus hemionus) in
      California. The moose adenovirus reported here may have been endemic in the
      captive moose herd, or infection may have resulted from either direct or indirect
      contact with other species of captive or wild cervids. This is the first report
      of adenoviral infection in moose and of the presence of adenoviral disease in a
      cervid in Canada.

PMID- 12216796
TI  - Subacute atropine toxicity in a pygmy sperm whale, Kogia breviceps.
AB  - Atropine, an anticholinergic agent commonly used in human and veterinary
      medicine, is reported to cause toxicity associated with its antimuscarinic
      action. A juvenile pygmy sperm whale, Kogia breviceps, was treated with atropine
      in an attempt to relieve symptoms similar to pyloric stenosis, as has been used
      in humans. Two doses of 0.01 mg/kg were given i.m., 12 hr apart, followed by
      three doses of 0.005 mg/kg i.m. s.i.d. over the next 3 days. Symptoms associated
      with atropine toxicity developed gradually and included hyperexcitability, a
      generalized ascending paralysis of body musculature, shallow, rapid respiration,
      vomiting, aspiration of seawater, and pulmonary edema. Treatment with
      physostigmine salicylate (two doses of 2 mg i.m., I hr apart) was effective in
      counteracting the paralysis, as well as other symptoms, beginning in as little as
      17 min after the first dose, and the whale was back to swimming on its own after
      8 hr. All overt symptoms of atropine toxicity were gone in about 24 hr, but there
      were other possible sequella that lasted much longer.

PMID- 12216798
TI  - Clinicopathologic features of suspected brevetoxicosis in double-crested
      cormorants (Phalacrocorax auritus) along the Florida Gulf Coast.
AB  - Outbreaks of morbidity and mortality in double-crested cormorants (Phalacrocorax
      auritus) along Florida's Gulf Coast have occurred sporadically for at least 30
      yr. During these outbreaks, the Clinic for the Rehabilitation of Wildlife,
      located on Sanibel Island in Florida, has admitted a substantial number of
      cormorants with consistent presentation of primarily neurologic clinical signs.
      In order to investigate the association of these outbreaks in cormorants with
      exposure to brevetoxin, we compared the timing of admittance of cormorants with
      outbreak-specific clinical signs to blooms of the brevetoxin-producing marine
      algae, Karenia brevis (formerly Gymnodinium breve), around Sanibel Island from
      1995 through 1999. The clinic admitted 360 out of 613 cormorants with the common
      clinical sign of severe cerebellar ataxia in six outbreaks occurring during this
      period. The ataxia was characterized by a broad-based stance, truncal
      incoordination, hypermetric gait, and intention tremors of the head. The
      histopathologic findings in 10 cormorants euthanized in 1997 were mild and
      nonspecific. An immunohistochemical staining technique for the detection of
      brevetoxin in cormorants documented the uptake of brevetoxin in tissues from four
      cormorants admitted during an outbreak in 1997, but a modified technique used on
      samples from 11 cormorants admitted during a K. brevis bloom in 2000 produced
      indeterminate results. Admittance of cormorants with outbreak-specific clinical
      signs was positively correlated (P < 0.05) with concurrent concentrations of K.
      brevis in local water. The cross-correlation coefficient was also significant
      when increased K. brevis levels preceded cormorant admittances by 2, 4, 6, and 8
      wk. This delay in time between K. brevis blooms and cormorant admittance and our
      clinical finding of neurologic abnormalities in cormorants without overt
      histopathologic features suggest an association between K. brevis blooms and
      local cormorant morbidity.

PMID- 12216799
TI  - Surgical castration and the effect on aggression in rock hyrax (Procavia
      capensis).
AB  - Lincoln Park Zoo acquired five intact, male rock hyraxes (Procavia capensis) from
      three separate institutions to exhibit as a group. The animals were of varying
      ages at the time of acquisition. During quarantine, all five were surgically
      castrated via a midline laparotomy technique in an attempt to reduce expected
      aggression within the group. Recommendations for successful castration, based on
      these five procedures, include performing the procedure on sexually immature
      hyraxes or sexually inactive adults, the use of a second surgeon during the
      procedure, and the use of stainless steel surgical clips for ligation of vessels
      and spermatic cord. Although combinations of the castrated animals coexisted for
      longer periods than those documented for other nonrelated male groups, aggression
      was significant and resulted in the death of one individual. Ultimately, all
      animals were housed individually.

PMID- 12216800
TI  - Positive effects of diet change on shedding of Salmonella spp. in the feces of
      captive felids.
AB  - A high prevalence of fecal Salmonella shedding in a collection of healthy exotic
      felids precipitated a change to two new commercially available feline diets. One
      year after initiation of the new diets, 18 fecal samples from individual felines,
      their exhibits, and representative samples of the diets were cultured for
      Salmonella spp. Only one culture grew a Salmonella sp. Salmonella uganda was
      cultured from the feces of one snow leopard (Felis uncia). Feeding a diet with
      minimal to no Salmonella contamination lowered Salmonella shedding rates in this
      collection of captive exotic felids.

PMID- 12216801
TI  - Shortfalls using second-generation anticoagulant rodenticides.
AB  - Second-generation anticoagulant rodenticides can give rise to unexpected
      casualties in nontarget species in zoos. The first two offspring of a pair of
      turkey vultures (Cathartes aura) died of brodifacoum toxicosis. The adult birds
      fed rodenticide-killed mice to their offspring. There are previous case reports
      of small carnivorous birds (Dacelo novae-guinae and Tockus deckeni) killed eating
      poisoned (difenacoum and brodifacoum) mice. Even a granivorous species (Rollulus
      roulroul) died, probably by contamination of its food by cockroaches that
      transported the rodenticide.

PMID- 12216802
TI  - Clinical challenge. Transitional vertebra at the lumbosacral junction.

PMID- 12216803
TI  - Field-based evaluation of biopesticide impacts on native biodiversity: malagasy
      coleoptera and anti-locust entomopathogenic fungi.
AB  - A community of 225 species of Coleoptera was used as a surrogate to evaluate
      nontarget effects of entomopathogenic fungi under development as biopesticides
      for use against the Malagasy migratory locust Locusta migratoria capito Saussure
      (Orthoptera: Acrididae). Evaluation of a standard chemical treatment of
      fenitrothion + esfenvalerate, two indigenous isolates of Metarhiziumflavoviride
      Gams & Roszsypol (SP3 and SP9), and an indigenous isolate of Beauveria bassiana
      (Balsamo) Vuillemin (SP16) against an untreated control in a replicated field
      trial in southern Madagascar showed that one of the isolates of M. flavoviride
      (SP3) and fenitrothion + esfenvalerate had distinct effects on nontarget beetle
      communities that were similar to each other. The other two isolates had no
      detectable effects compared with the untreated control. Based on an evaluation of
      the species affected, the similar effects of SP3 and the chemical pesticide are
      hypothesized to be the result of a perturbation of predator-prey relationships,
      with a distinct tendency to be manifested via predators. The data indicate that
      use of SP9 and SP16 would have minimal detrimental effects on the biodiversity of
      nontarget beetles, but that SP3 needs further testing.

PMID- 12216804
TI  - Effect of neem seed extract on feeding, growth, survival, and reproduction of
      Diaprepes abbreviatus (Coleoptera: Curculionidae).
AB  - A commercially available neem seed extract, Neemix 4.5, containing 4.5%
      azadirachtin (AZA), was assessed for biological activity against the root weevil
      Diaprepes abbreviatus (L.), an important exotic insect pest of Florida citrus.
      Laboratory bioassays against neonatal and 3-wk-old larvae fed sliced carrot
      treated with Neemix produced dose-dependent larval mortality and reduced fresh
      weights among survivors of treatments. The weight response was greater than the
      mortality response for both larval age groups. Neonates treated with 45 mg/liter
      AZA weighed 60% less than those in the control after 4 wk. Three-week-old larvae
      treated with 45 mg/ liter AZA weighed 30% less than those in the control after 5
      wk. When neonates were exposed to insect diet incorporated with Neemix,
      reductions in larval survival and weight were observed at concentrations as low
      as 4.8 mg/liter AZA after 6 wk. Larval growth was inhibited by >97% with 42.9
      mg/liter AZA in the diet. A soil drench containing 30 mg/liter AZA reduced the
      survival and weight gain of neonates added to potted citrus and provided
      protection to the roots in a greenhouse experiment. A concentration of 90
      mg/liter AZA was required to provide protection of citrus roots against 4-wk-old
      larvae. Reproductive effects were observed when adult weevils were fed foliage
      treated with Neemix. The numbers of larvae hatching per egg mass were reduced by
      27% and 68% at 30 and 90 mg/liter AZA, respectively. These results suggest that
      Neemix should be further evaluated for use in integrated pest management (IPM)
      programs of citrus.

PMID- 12216805
TI  - In vivo rearing of Thripinema nicklewoodi (Tylenchida: Allantonematidae) and
      prospects as a biological control agent of Frankliniella occidentalis
      (Thysanoptera: Thripidae).
AB  - Methods are described for the in vivo production of the nematode Thripinema
      nicklewoodi (Siddiqi), an obligate parasite and potential biological control
      agent of western flower thrips Frankliniella occidentalis (Pergande). Nematode
      infection is not lethal but causes sterilization of adult female hosts. Both
      fertilization and horizontal transmission of T. nicklewoodi is achieved in 1.5-ml
      microcentrifuge tubes (infection arenas), in the presence of 100% humidity, a
      temporary food source and preferably a damp substrate. Following exposure to
      infection arenas, F. occidentalis are reared on excised bean leaves Phaseolus
      vulgaris (L.) in polypropylene containers for 2 wk at 25 degrees C to allow the
      reproduction and development of a single generation of nematodes within infected
      hosts's abdominal cavity. To identify infected hosts after this incubation
      period, thrips are isolated in microcentrifuge tubes and monitored for free
      living nematodes being released along with frass. Infected thrips are
      reintroduced back into infection arenas to inoculate further thrips to maintain
      the culture. We documented the output of the rearing procedure using a standard
      method and following simple manipulation of several individual parameters of the
      infection technique. The standard method was the most efficient, and resulted in
      an increased (output/input) ratio of infected thrips of approximately 2; i.e.,
      the number of infected thrips approximately doubles each generation. Monitoring
      infected thrips revealed that nematodes were first released between 12-14 d
      postinfection and for an average of 7.9 d at 25 degrees C; highlighting the
      potential to reuse infective thrips between infection arenas. The possibility of
      using T. nicklewoodi as an inoculative agent against F. occidentalis infesting
      floricultural crops is discussed.

PMID- 12216806
TI  - Pathogenicity of Beauveria bassiana, Metarhizium anisopliae (Deuteromycotina:
      Hyphomycetes), and other entomopathogenic fungi against Lygus lineolaris
      (Hemiptera: Miridae).
AB  - The pathogenicity of 32 fungal isolates from the genera of Beauveria,
      Verticillium, Paecilomyces, Metarhizium, Mariannaea, and Hirsutella to second
      instar tarnished plant bug, Lygus lineolaris (Palisot de Beauvois), was tested
      under laboratory conditions. These isolates originated from various insect hosts
      and substrates from France, Denmark, Austria, Italy, Turkey, Syria, and the
      United States. A single exposure concentration (1 x 10(7) conidia/ ml) assay for
      each isolate was first conducted by immersing the insects in 10 ml of a fungal
      suspension for 5s. These were followed by concentration-mortality assays on five
      of the most pathogenic isolates using four test concentrations ranging from 2 x
      10(4) to 2 x 10(7) conidia/ml. B. bassiana 726 (Bemisia-passaged GHA strain) was
      used as a standard for comparison in all of the assays. Among the test isolates,
      three produced mortality not significantly different from the water control.
      Mortality ranged from 35 to 98% among the other 29 isolates. The LC50 values of
      the five most pathogenic isolates ranged from 0.8 to 5.0 x 10(5) conidia/ml. The
      LT50 values for these isolates ranged from 6.0 to 6.9, 3.1 to 5.1, and 2.5 to 4.0
      d for concentrations of 2 x 10(5), 2 x 10(6), and 2 x 10(7) conidia/ml,
      respectively. Two strains of B. bassiana (ARSEF 1394,5665) and one M anisopliae
      (ARSEF 3540) were more pathogenic to the nymphs than the standard, having
      significantly lower LC50 and LT50, values. Our results demonstrated that several
      genera of entomopathogenic fungi have promise as microbial control agents against
      L. lineolaris.

PMID- 12216807
TI  - Conservation of predatory arthropods in cotton: role of action thresholds for
      Bemisia tabaci (Homoptera: Aleyrodidae).
AB  - Studies were conducted in 1994 and 1995 to examine the effects of a range of
      action thresholds for managing Bemisia tabaci (Gennadius) Biotype B (= B.
      argentifolii Bellows & Perring) with insecticides in cotton on populations of
      arthropod predators in Imperial Valley, CA, and Maricopa, AZ. Application of
      insecticides significantly reduced population densities of spiders, Geocoris
      punctipes (Say), G. pallens (Stal), Orius tristicolor (White), Nabis alternatus
      Parshley, Zelus renardii Kolenati, Hippodamia convergens Guerin-Meneville,
      Spanogonicus albofasciatus (Reuter), Drapetis sp., and Chrysoperla carnea
      Stephens in one or both years and sites compared with untreated controls. Use of
      higher B. tabaci thresholds conserved some species and groups relative to lower
      thresholds. Stepwise regression analyses indicated that reductions in predator
      populations were generally influenced more strongly by the timing of the first
      insecticide application than by the total number of sprays necessary to maintain
      suppression of the pest below any given action threshold. A predation index,
      which weights the importance of each predator species based on their known
      frequency of predation on B. tabaci and another key pest, Pectinophora
      gossypiella (Saunders), was developed and analyzed. Patterns were similar to
      results based on changes in abundance alone, but the index generally revealed
      less severe effects of insecticides on overall predator function. The current
      action threshold for conventional insecticidal control of B. tabaci in Arizona
      and southern California is five adults per leaf. Results here suggest that
      predator conservation may be enhanced by raising the initial threshold to delay
      the first application or initially using more selective materials such as insect
      growth regulators.

PMID- 12216808
TI  - Unusual acetylenic sex pheromone of grape leaffolder (Lepidoptera: Pyralidae).
AB  - The female-produced sex pheromone of grape leaffolder, Desmia_funeralis (Hubner),
      has been identified as a blend of (Z,Z)-11,13-hexadecadienal, 11-hexadecynal, and
      (Z)-11-hexadecenal. The first two components were essential for attraction of
      male moths, whereas the third compound was not essential, but increased trap
      catches approximately twofold when added in appropriate doses to the optimum
      blend of the other two components. In field tests, male moths were trapped
      equally well in traps baited with pheromone doses of 0.2 to >6 mg, and lures
      remained attractive for at least 5 wk.

PMID- 12216809
TI  - Influence of temperature on developmental rate, wing length, and larval head
      capsule size of pestiferous midge Chironomus crassicaudatus (Diptera:
      Chironomidae).
AB  - Larvae of Chironomus crassicaudatus Malloch were reared individually at nine
      constant temperatures from 12.5 to 32.5 degrees C (2.5 degrees C increments) for
      120 d. Duration of immature stages (egg, four instars, and pupa), head capsule
      width of fourth instars, and wing length were recorded. Some adults emerged at
      all temperatures, except at 12.5 degrees C where individuals developed to fourth
      instars during the experiment. Sharpe and DeMichele's four-parameter model with
      high-temperature inhibition described the temperature-dependent developmental
      rates. The slowest development was observed at 15 degrees C, with developmental
      rate peaking between 25 and 27.5 degrees C. Developmental rate increased rapidly
      with increasing temperature up to 20 degrees C, slowed between 20 and 27.5
      degrees C, and decreased at temperatures >27.5 degrees C. No developmental
      inhibition at high temperatures was observed in eggs. The most apparent high
      temperature inhibition of development was recorded in fourth instars, which
      comprised the largest proportion of developmental time. Males developed faster
      than females, but females had wider larval head capsules and longer wings than
      males. Adult size was negatively related with temperature in both sexes, but this
      relationship was steeper in males than in females. Larval size peaked at 20
      degrees C, whereas the head capsule width was reduced at temperatures higher and
      lower than 20 degrees C.

PMID- 12216810
TI  - Development and optimization of methods for using sex pheromone for monitoring
      the mealybug Planococcus ficus (Homoptera: Pseudococcidae) in California
      vineyards.
AB  - The sex pheromone of the vine mealybug Planococcus ficus Signoret has been
      identified as a single component, lavandulyl senecioate. Racemic lavandulyl
      senecioate was as attractive to male mealybugs as the insect-produced (S)
      enantiomer, indicating that the unnatural enantiomer is not inhibitory.
      Lavandulol, which also was found in extracts from virgin females, antagonized
      attraction of males at higher doses. Rubber septum lures loaded with 10- to 1,000
      microg doses of the pheromone were equally attractive, and lures loaded with 100
      microg of racemic pheromone remained attractive for at least 12 wk under field
      conditions. Delta traps were more effective than double-sided sticky cards and
      minimized captures of nontarget insects. Pheromone-baited traps had an effective
      range of at least 50 m. Comparison of visual sampling methods and sampling of
      males with pheromone-baited traps revealed that trap catches were significantly
      correlated with the results from visual sampling methods, and with economic
      damage.

PMID- 12216811
TI  - Flooding influences ovipositional and feeding behavior of the rice water weevil
      (Coleoptera: Curculionidae).
AB  - The rice water weevil, Lissorhoptrus oryzophilus Kuschel, is the most destructive
      insect pest of rice in the United States. As part of an effort to develop
      strategies to manage this pest, the ovipositional and feeding habits of L.
      oryzophilus on rice plants subjected to different flooding treatments were
      characterized in greenhouse studies. Presence and depth of flood had a direct
      influence on the ovipositional behavior of weevils in no-choice studies. More
      eggs were found in flooded plants than in unflooded plants. Moreover, plants
      flooded to a depth of 5.1 cm received more eggs than plants flooded to depths of
      1.3 or 10.2 cm. Presence and depth of flood influenced both the proportion of
      females that oviposited in plants and the number of eggs laid by those females
      that did oviposit. In choice studies, female weevils showed a marked
      ovipositional preference for plants flooded to a depth of 10.2 cm over unflooded
      plants and plants flooded to a depth of 1.3 cm. In separate choice experiments,
      adult rice water weevils fed more on flooded plants than on unflooded plants. In
      a third set of experiments, flooded plants were taller and had higher
      concentrations of 10 of 13 plant nutrients than unflooded plants. Thus, flooding
      may influence rice water weevil behavior both directly, by acting as a stimulus
      for feeding or oviposition, and indirectly, by inducing changes in the
      suitability of rice plants for feeding or oviposition. These data suggest that it
      may be possible to manipulate populations of weevils in rice by changing water
      management practices.

PMID- 12216813
TI  - Fecundity in twospotted spider mite (Acari: Tetranychidae) is increased by direct
      and systemic exposure to imidacloprid.
AB  - The effect of imidacloprid on fecundity in twospotted spider mites, Tetranychus
      urticae Koch, was investigated in laboratory experiments using individual females
      on bean leaf discs. Mites were directly exposed to spray formulations of
      imidacloprid or fed on discs cut from a systemically treated bean plant.
      Imidacloprid-treated T. urticae produced 10-26% more eggs during the first 12 d
      of adult life and 19-23% more during adulthood compared with a water-only
      treatment. Increased egg production occurred immediately after exposure and
      lasted for about 15 d in sprayed mites. In mites exposed to imidacloprid by
      ingestion, increased egg production was not apparent until after 6 d and lasted
      until about day 18. Longevity was significantly greater in mites that ingested
      imidacloprid but not in sprayed mites. The significance and importance of
      imidacloprid-stimulation of fecundity in T. urticae to pest management in crop
      systems like hops, which routinely use this insecticide, is discussed.

PMID- 12216812
TI  - Hazards of insecticides to the bumble bees Bombus impatiens (Hymenoptera: Apidae)
      foraging on flowering white clover in turf.
AB  - Insecticides used on turf are sometimes applied to areas with flowering weeds
      that attract honey bees and native pollinators. We tested residual effects of
      such treatments on colony vitality and behavior of the bumble bees Bombus
      impatiens Cresson foraging on turf containingwhite clover, Trifolium repens L.
      Imidacloprid, a syst emic chloronicotinyl used for preventive control of root
      feeding grubs, was applied as granules, followed by irrigation, or sprayed as a
      wettable powder, with or without irrigation. Hives were confined on the plots in
      large field cages after residues had dried and colony vitality (i.e., numbers of
      brood, workers, and honey pots, and weights of queens, workers, and whole
      colonies with hives) was evaluated after 28-30 d. Workers' foraging activity and
      defensive response to an aggressive stimulus also were evaluated. In another
      test, weedy turf was sprayed with chlorpyrifos, carbaryl, or cyfluthrin at
      labeled rates for surface-feeding pests. Bee colonies were confined on the plots
      after residues had dried, with effects on colony vitality evaluated after 14 d.
      Finally, foraging activity of wild bumble bees was monitored on open plots to
      determine if insecticide-treated areas were avoided. Imidacloprid granules, and
      imidacloprid sprays applied with posttreatment irrigation, had no effect on
      colony vitality or workers' behavior, suggesting that such treatments pose little
      systemic or residual hazard to bumble bees. In contrast, exposure to dry
      nonirrigated residues of all of the aforementioned insecticides had severe impact
      on colony vitality. Foraging workers did not avoid insecticide-treated areas.
      Means by which turf managers can reduce hazards of insecticide applications to
      pollinators are discussed.

PMID- 12216814
TI  - Bemisia tabaci (Homoptera: Aleyrodidae) biotype B colonization on okra- and
      normal-leaf upland cotton strains and cultivars.
AB  - We compared smooth-leaf okra- and normal-leaf upland cotton (Gossypium hirsutum
      L.) strains and cultivars for susceptibility to colonization by Bemisia tabaci
      (Gennadius) biotype B. Experiments were conducted at seven field sites, five at
      Holtville, CA, and two at Maricopa, AZ, during 1996-2000. Okra-leaf strains and
      cultivars, as a group, had lower numbers of adults, eggs, and nymphs compared
      with normal-leaf strains and cultivars indicating the potential of okra-leaf
      genetic traits for reducing colonization by B. tabaci. Results also suggest that
      okra-leaf shape may provide less favorable micro-environmental conditions for the
      habitat of B. tabaci because of more open canopy as evidenced by higher leaf
      perimeter to leaf area ratio. The okra-leaf cultivar 'Siokra L-23' appears to
      have genetic traits that should be examined further as a source of B. tabaci
      resistance.

PMID- 12216815
TI  - Temporal distribution of Chaetocnema pulicaria (Coleoptera: Chrysomelidae)
      populations in Iowa.
AB  - In 1999 and 2000, yellow sticky cards and sweep net samples were used to document
      the occurrence of an overwintering adult generation of Chaetocnema pulicaria
      Melsheimer, corn flea beetle, followed by two distinct populations peaks during
      the growing season in Iowa Emergence of the overwintering adult generation
      started in mid-April and continued until early June in both years, with
      populations as high as 45 +/- 7.9 per 10 sweeps. Periods that ranged from 14 to
      32 d were observed in 1999 and 2000 when C. pulicaria was not found following the
      overwintering generation. The first summer peak of C pulicaria was observed
      between the end of June into the middle of July, with the highest observed peak
      at 16.70 +/- 1.42 C. pulicaria per 10 sweeps in cornfields. The second summer
      peak of C pulicaria was observed between the middle into early September, with
      populations as high as 27.80 +/- 2.76 C. pulicaria per 10 sweeps. During the
      growing season, more C. pulicaria were caught on yellow sticky cards originating
      from soybean borders than from grass borders. There were significantly greater
      numbers of C. pulicaria on yellow sticky cards located in grass borders adjacent
      to cornfields at the end of the growing season, compared with yellow sticky cards
      located within cornfields, indicating the movement of C. pulicaria from the
      cornfield back into the grass borders at the end of the growing season. In 2000,
      from August to the end of the corn growing season, significantly more C.
      pulicaria were found in grass borders than in the cornfields. Based on this new
      quantitative information, planting time could be altered to avoid the emergence
      of the overwintering generation of C. pulicaria. In addition, knowledge
      concerning the seasonalities of the first and second population peaks of C
      pulicaria during the corn growing season could be used to recommend optimal
      timing for foliar-applied insecticide applications. This new knowledge concerning
      the seasonal dynamics of C pulicaria will help to improve management
      recommendations for Stewart's disease of corn, caused by the bacterium Pantoea
      stewartii, and that is vectored by C pulicaria.

PMID- 12216816
TI  - Alfalfa weevil (Coleoptera: Curculionidae) larval sampling: comparison of shake
      bucket and sweep-net methods and effect of training.
AB  - Two field-sampling methods, shake-bucket and sweep-net, were compared for use in
      monitoring alfalfa weevil, Hypera postica (Gyllenhal), larvae in alfalfa hay of
      the high plains and intermountain region of North America. In this region,
      alfalfa grows to sufficient height to use both methods before the more damaging
      late instars peak in abundance. Both methods also were compared with extracting
      larvae by using Berlese funnels in the laboratory. The shake-bucket method was
      more sensitive in detecting small larvae (first and second instars) than large
      larvae (third and fourth instars), and the sweep-net method detected a lower
      proportion of small larvae. The number of larvae collected with the shake-bucket
      method was strongly correlated with number of larvae recovered from Berlese
      funnels (total larval counts, R2 = 0.85). Correlation of the sweep-net samples
      with the Berlese extraction was also significant but less strong (R2 = 0.56). In
      addition, sampler instruction was evaluated to determine whether demonstration
      training affects performance of inexperienced samplers using the two field
      sampling methods. Training did not significantly change sampler performance in
      using the shake-bucket but did increase the number of large larvae when using the
      sweep-net. In addition, less variability was associated with the shake-bucket
      sampling method than with the sweep-net method for samplers who only had access
      to written sampling instructions. Therefore, when estimation of small larval
      abundance is desired for economic decision-making and sampling is performed by
      people with little or infrequent sampling experience, such as growers, the shake
      bucket method is the preferred field-sampling method in the high plains and
      intermountain region of North America Sweep-net sampling is more variable than
      shake-bucket sampling, although demonstration training improves the usefulness of
      the sweep-net.

PMID- 12216817
TI  - Effects of kaolin-based particle film application on boll weevil (Coleoptera:
      Curculionidae) injury to cotton.
AB  - This study examined a non-insecticidal tactic for suppressing boll weevil,
      Anthonomus grandis grandis Boheman, damage to cotton, Gossypium hirsutum L. In
      cage assays, kaolin, a reflective white mineral, applied to excised cotton
      squares or to the cotton foliage, initially resulted in lower levels of boll
      weevil injury to squares than nontreated squares. Boll weevil oviposition and
      feeding on kaolin-treated squares and squares on kaolin-treated cotton plants
      increased when nontreated squares and cotton plants were in short supply. A
      laboratory assay and field trials suggested that boll weevils distinguished
      between cotton plots based on color differences caused by kaolin and this
      appeared to influence levels of damage to squares. Random sampling in small plots
      indicated that oviposition damage to squares in plots treated with kaolin was
      reduced (P < 0.05) compared with nontreated controls, except when rain washed the
      kaolin off the foliage. Lint yield differences were not detected between the
      small plots, but the kaolin-treated small plots yielded as much as 2.36 times
      more cotton lint than a large but unreplicated adjacent nontreated control plot,
      and up to 1.39 times more than another large but unreplicated adjacent plot
      sprayed twice with preemptive applications of azinphosmethyl when cotton squares
      were first developing (pinhead stage). Potentially important avenues for future
      research on boll weevil injury suppression using kaolin are discussed.

PMID- 12216818
TI  - Behavior of bollworm (Lepidoptera: Noctuidae) larvae on genetically engineered
      cotton.
AB  - Reports of bollworm, Helicoverpa zea (Boddie), larvae feeding in white flowers of
      Bollgard cotton have been relatively common since the commercialization of this
      technology in 1996. Field studies were conducted in Louisiana to determine if
      differences in bollworm larval behavior occuron non-Bollgard (cultivar 'Deltapine
      5415') and Bacillus thuringiensis (Bt), Bollgard ('NuCOTN 33B') cottons. Larvae
      were placed on the terminal foliage of either single cotton plants or on all
      plants within 1-m row micro-plots. On preflowering cotton plants, significantly
      more bollworms moved from the site of infestation (terminal) on Bollgard plants
      compared with that on non-Bollgard plants. On individual flowering plants, the
      number of nodes larvae moved from the terminal and the number of infested bolls
      was greater on Bollgard cotton plants. Similar differences between Bollgard and
      non-Bollgard plants in the percentage of infested terminals and squares were
      observed at 48-h after infestation when 1-m rows were infested. These data will
      be used to refine scouting protocols for bollworm larvae on Bollgard cotton.

PMID- 12216819
TI  - Measuring the impact of Leptoglossus occidentalis (Heteroptera: Coreidae) on seed
      production in lodgepole pine using an antibody-based assay.
AB  - We measured the impact of Leptoglossus occidentalis on seed production in
      lodgepole pine, Pinus contorta variety latifolia Engelmann, using an antibody
      marker developed to detect residual saliva in fed-on seeds. Nymphs, adult
      females, and adult males were caged on cones during early, mid- and late season
      cone development. Individual analysis of 12,887 seeds extracted from 365 cones
      revealed that 37.3% seeds tested positive for seed bug saliva. The antibody assay
      was 38 times more effective than radiography at detecting seed bug damage.
      Radiography can detect partially emptied seed but cannot discriminate between
      aborted seeds and those emptied by seed bugs. The antibody marker was least
      sensitive in detecting early season damage compared with mid- and late season
      damage. We hypothesize that residual saliva in seeds fed on early in the season
      was either absorbed by the damaged seed or degraded over time. Early season
      feeding resulted in the greatest number of seeds fused to cone scales and the
      extraction efficiency for cones exposed to feeding during this time was reduced
      by 64% compared with control cones. Adding fused seeds to antibody-positive seeds
      raised the proportion of damaged seeds to 48.3%. At all stages of cone
      development, adult females were the most destructive life stage, damaging up to
      two seeds per day late in the season. When seed losses were adjusted to damage
      per degree-day, female damage was greatest early in the season, while males
      caused the same amount of damage regardless of cone development period. The
      results of the antibody assay provide baseline data for developing damage
      prediction formulae, and establish L. occidentalis as a potentially serious pest
      in lodgepole pine seed orchards.

PMID- 12216820
TI  - Elution rate and spacing of antiaggregation pheromone dispensers for protecting
      live trees from Dendroctonus pseudotsugae (Coleoptera: Scolytidae).
AB  - The antiaggregation pheromone 3-methylcyclohex-2-en-1-one (MCH) is highly
      effective in preventing the infestation of high-risk trees by Douglas-fir beetle,
      Dendroctonus pseudotsugae Hopkins. A large portion of the cost of an MCH
      treatment is related to the time applicators spend walking through an area
      dispersing the formulated pheromone. Application of fewer MCH dispensers eluting
      at a higher rate than those currently registered for operational use could
      potentially reduce treatment costs. Two higher elution rates, 6 and 18 mg/d per
      dispenser, were compared with the current standard of 2 mg/d per dispenser and an
      untreated control on 1-ha circular plots. Dispensers were spaced 5,15, and 44 m
      apart around the plot perimeters eluting 2, 6, and 18 mg/d, respectively. The
      nominal dose of MCH was 144 mg/ha/d on all plots. Percentages of Douglas-fir
      trees > or = 20 cm diameter at breast height mass attacked by Douglas-fir beetle
      were significantly lower on plots treated with dispensers eluting 2 and 6 mg/d
      and spaced 5 and 15 m apart, respectively, compared with the untreated control.
      Infestation rate on plots treated with dispensers eluting 18 mg/d and spaced 44 m
      apart was not significantly different from the control. Douglas-fir beetle
      abundance and host tree availability were similar on all plots. These results
      indicate that MCH dispensers eluting 6 mg/d (three times the current standard
      rate) and spaced 15 m apart (three times existing standard distance) can
      effectively prevent Douglas-fir beetle infestations.

PMID- 12216821
TI  - Particle film affects black pecan aphid (Homoptera: Aphididae) on pecan.
AB  - Three species of aphids attack pecan foliage, Carya illinoensis (Wang.) K. Koch,
      and cause economic damage. We tested a kaolin-based particle film against one of
      these aphid species, black pecan aphid, Melanocallis caryaefoliae (Davis). Effect
      of particle film on host selection, adult mortality, and production of nymphs by
      M. caryaefoliae was tested on seedling pecans in the laboratory. Fewer M.
      caryaefoliae adults selected treated foliage compared with untreated foliage. A
      higher percentage of adults that did select treated foliage were recovered from
      upper leaf surfaces compared with the percentage of adults recovered from upper
      leaf surfaces of untreated leaves. Observations with a microscope revealed an
      accumulation of particle film on aphid body parts, especially on tarsi, and
      strongly suggests that aphid mobility was restricted. Adult mortality was higher
      on treated foliage and led to an overall decrease in production of nymphs on
      those seedlings. In addition, we measured spectral properties of treated seedling
      pecan foliage. Light reflectance by treated foliage was increased and absorptance
      decreased compared with control foliage whereas transmittance of light through
      control and particle film-treated leaves was similar. We did not detect any
      phytotoxic effect on pecan due to application of particle film.

PMID- 12216822
TI  - Comparing an IPM pilot program to a traditional cover spray program in commercial
      landscapes.
AB  - An integrated pest management (IPM) pilot program for landscape plants was
      implemented during 1997 and 1998 on two commercial, two residential, and one
      institutional property managed by landscape professionals. When compared with
      preprogram, calendar-based cover spray program costs at these sites in 1996, the
      IPM program was cost-effective at one of the five sites in both 1997 and 1998,
      and cost effective at a second additional site in 1998 when the cooperator,
      initially skeptical of IPM, discontinued calendar-based cover sprays performed in
      1996 and 1997. The mean cost per site was $703.40 (preprogram), $788.26, and
      $582.22 in 1996, 1997, and 1998, respectively. Volume of pesticide applied
      decreased a mean of 86.3% on the four sites not receiving cover sprays and
      increased 2.3% at site 2 (still using cover sprays) in 1997. In 1998, pesticide
      volume was reduced an average of 85.3% at all five sites compared with preprogram
      levels. The majority of insect pest problems were corrected using spot sprays of
      insecticidal soap or horticultural oil or by physical means such as pruning. One
      third of the woody plant material on the commercial and institutional sites
      consisted of holly, juniper, and azalea. The most prevalent pests encountered
      were mites (Tetranychidae), aphids, lace bugs, scales, whiteflies, and Japanese
      beetle. Spiders were the most abundant group of predatory arthropod and ants,
      green lacewings, and lady beetles were also well represented in the managed
      landscapes.

PMID- 12216823
TI  - Pear transformed with a lytic peptide gene for disease control affects nontarget
      organism, pear psylla (Homoptera: Psyllidae).
AB  - The biology and behavior of pear psylla, Cacopsylla pyricola Foerster, on a
      transgenic clone of 'Bartlett' pear, Pyrus communis L., containing a synthetic
      antimicrobial gene, D5C1, was compared with that of a nontransgenic parental
      clone to determine whether there were any nontarget effects. The gene construct
      also contained the marker gene nptII (aminoglycoside 3'-phosphotransferase II)
      that encodes for antibiotic resistance to identify transformed plants. The
      purpose of the original transformation was to enhance pear resistance to the
      bacterial disease fireblight caused by Erwinia amylovora (Burr.) Winslow et al.
      The biology and behavior of pear psylla on a transgenic clone were compared with
      a nontransgenic parental pear clone in short- (< or = 7-d) and long-term (32-d)
      studies. Short-term studies indicated pear psylla adults preferred to settle and
      oviposit, and nymphs fed more and developed slightly faster, on transgenic pear
      compared with nontransgenic pear. In contrast, a long-term study on psylla colony
      development showed considerably fewer eggs, nymphs, and adults were produced on
      transgenic pear. Although adults reared on transgenic pear did not have weight
      affected, females produced fewer eggs and nymphal hatch was significantly reduced
      on the transgenic pear clone. Our results suggest that pear psylla biology and
      behavior are initially enhanced on this transgenic pear clone. However, chronic
      exposure of psylla populations to transformed pear plants that express the nptII
      marker and lytic peptide genes had detrimental effects on pear psylla
      reproductive biology. Field studies would be required to determine the specific
      effects of each gene on pear psylla biology and behavior and whether these
      effects would be expressed under natural conditions. The four-fold reduction in
      psylla population levels that resulted on this disease resistant transgenic pear
      line would be an added benefit to a pear integrated pest management (IPM)
      program. Overall, this study demonstrates that genetically altering plants to
      control one particular organism can have unintentional yet beneficial effects
      against other nontarget pest organisms in agricultural crops.

PMID- 12216824
TI  - Development and implementation of a reduced risk peach arthropod management
      program in New Jersey.
AB  - We implemented a 2-yr program to reduce organophosphorus and carbamate
      insecticide use and mitigate their associated risks as they relate to peach
      production in New Jersey and elsewhere. The main thrust integrated mating
      disruption with ground cover management practices to reduce oriental fruit moth,
      Grapholita molesta (Busck) (Lepidoptera: Tortricidae), and tarnished plant bug,
      Lygus lineolaris (Palisot de Beauvois) (Heteroptera: Miridae), abundance and
      damage. This Reduced Risk Peach Arthropod Management Program was compared with
      adjacent conventionally managed peach orchards. In 1999, we found 2.3 times fewer
      L. lineolaris and stink bugs (Euschistus servus (Say), E. tristigmus (Say),
      Acrostemum hilare (Say) (Heteroptera: Pentatomidae) and 2.0 times less
      heteropteran damaged peaches in reduced-risk orchards when compared with
      conventionally managed orchards. In 2000, we observed 4.9 times fewer
      heteropteran insects in reduced-risk orchards but damage levels were not
      significantly different between the two programs. In both years, G. molesta
      mating disruption gave at least 4 mo of noninsecticidal control of this major
      pest. The reduced-risk program provided a level of pest control that was equal to
      or better than conventional peach pest management programs while using fewer
      organophosporus and carbamate insecticides.

PMID- 12216825
TI  - Acetylcholinesterase mediated susceptibility of soldiers and workers of formosan
      subterranean termite (Isoptera: Rhinotermitidae) to chlorpyrifos.
AB  - Target site studies were undertaken to examine the difference in susceptibility
      of Formosan subterranean termite, Coptotermes formosanus Shiraki, workers and
      soldiers to chlorpyrifos. Workers exhibited significantly greater
      acetylcholinesterase activity per insect than soldiers (118.63 +/- 48.51 versus
      47.98 +/- 22.59 mOD/min/insect equivalent). Likewise, enzyme activity (mean +/-
      SD) per milligram of protein was greater in workers than soldiers (440.30 +/-
      267.43 versus 311.53 +/- 149.83 mOD/min/mg protein). The enzyme of soldiers was
      more sensitive to the acetylcholinesterase (AChE) inhibitors eserine and
      chlorpyrifos-oxon than that of workers. The I50s of chlorpyrifos-oxon were 2.66
      and 4.59 nM for soldiers and workers, respectively, whereas the I50s of eserine
      were 16.56 and 25.41 nM for soldiers and workers, respectively. The amount of
      protein was significantly higher in workers than in soldiers with mean values of
      0.270 +/- 0.102 and 0.154 +/- 0.054 mg/insect equivalent, respectively. We
      suggest that the differential response of workers and soldiers to chlorpyrifos
      may be due to the difference in AChE sensitivity to inhibition and the amount of
      protein between them.

PMID- 12216826
TI  - Resistance and cross-resistance to four insecticides in populations of
      obliquebanded leafroller (Lepidoptera: Tortricidae).
AB  - Populations of obliquebanded leafroller, Choristoneura rosaceana (Harris), were
      collected from organic and conventionally managed orchards located in the
      Okanagan and Similkameen Valleys of British Columbia Neonate F1 progeny were
      assayed for resistance to azinphosmethyl, tebufenozide, methoxyfenozide, and
      indoxacarb using a leaf disk bioassay. Significant differences in resistance
      levels among populations were observed for all four insecticides. Insects
      collected from organic sites were more susceptible to all insecticides than were
      insects collected from conventional sites. Resistance to the benzoylhydrazine
      insect growth regulators tebufenozide and methoxyfenozide was highly correlated
      with resistance to azinphosmethyl across populations, indicating cross-resistance
      between these compounds. The highest levels of resistance were observed with
      indoxacarb, but resistance levels to indoxacarb did not correlate with those for
      azinphosmethyl. Dose-response regression lines for tebufenozide were parallel
      across populations, suggesting that the resistance mechanism(s) were
      quantitatively, but not qualitatively, different. Cross-resistance between
      azinphosmethyl and benzoylhydrazine insecticides indicates that a resistance
      management strategy for obliquebanded leafroller involving the rotation of these
      materials is not likely to be successful.

PMID- 12216827
TI  - Resistance monitoring of Helicoverpa armigera (Lepidoptera Noctuidae) to Bacillus
      thuringiensis insecticidal protein in China.
AB  - Sensitivities of Helicoverpa armigera (Hubner) field populations to Bacillus
      thuringiensis (Bt) insecticidal protein CrylAc were monitored during 1998-2000 in
      China. A total of 41 strains was sampled, and most of them were collected from Bt
      cotton planting regions. The range of IC50 values (concentration producing 50%
      inhibition of larval development to third instar) among different populations in
      1998,1999, and 2000 were 0.020-0.105 microg/ml, 0.016-0.099 microg/ml, and 0.016
      0.080 microg/ml, respectively. Diagnostic concentration studies (IC99) showed
      that the percentage of individuals reaching third instar ranged from 0 to 4.35%,
      with only eight of the 41 tested populations showing values above 0%. Also
      interesting was a trend over successive years in which fewer populations
      contained individuals that survived the diagnostic concentration by reaching
      third instar. Considering these data, it was determined that the field
      populations sampled during the 3-yr study were susceptible to CrylAc protein, and
      that movement toward resistance among H. armigera populations was not apparent.

PMID- 12216828
TI  - Evaluation of the natural refuge function for Helicoverpa arnigera (Lepidoptera:
      Noctuidae) within Bacillus thuringiensis transgenic cotton growing areas in north
      China.
AB  - The density of Helicoverpa armigera (Hubner) populations on Bacillus
      thuringiensis Berliner (Bt) transgenic cotton, corn, peanut, and soybean;
      differences in its development on Bt cotton and common (nontransgenic) cotton;
      and the potential for mating among populations from Bt cotton fields and other
      crop fields were investigated in the suburbs of Xinxiang City (Henan Province)
      and Langfang City (Hebei Province) in the southern and northern parts of north
      China, respectively. Although development of H. armigera on Bt cotton was much
      slower than on common cotton, there was a still high probability of mating
      between populations from Bt cotton and other sources due to the scattered
      emergence pattern of H. armigera adults, and overlap of the second and third
      generations. In a cotton and corn growing region, early and late planted corn
      provided suitable refugia for the third and fourth generations of H. armigera,
      but not for the second generation. In a cotton and soybean/ peanut mix system,
      noncotton crops provided a natural refugia from the second- to fourth-generation
      H. armigera, but function of the refuge would closely depend on the proportion of
      Bt cotton. Consequently, it may be necessary to compensate the original mixed
      cropping patterns in different areas for delaying resistance development of H.
      armigera to Bt cotton.

PMID- 12216830
TI  - Resistance to adult banded cucumber beetle (Coleoptera: Chrysomelidae) in romaine
      lettuce.
AB  - Four cultivars of lettuce, Lactuca sativa L., were evaluated for their resistance
      to the adult banded cucumber beetle, Diabrotica balteata LeConte, under
      laboratory conditions. When paired with each of the other three cultivars, leaf
      consumption in all possible combinations of short-term (48 h) two-choice tests
      among the cultivars was significantly reduced only for 'Valmaine'. However, in a
      48-h no-choice situation, beetles fed Valmaine or 'Short Guzmaine' had similarly
      low leaf consumption, followed by 'Parris White', with the greatest consumption
      occurring on 'Tall Guzmaine'. In longer term experiments, female beetles fed
      Valmaine for 10, 13, or 16 d generally had lower survival and the lowest body
      weights compared with beetles fed any of the other three cultivars. No mature
      eggs were found in the ovaries of females fed Valmaine, whereas from 14% (Short
      Guzmaine, day 10) to 100% (Tall Guzmaine, day 13) of females fed the other
      cultivars produced mature eggs. In a starvation test, most D. balteata of either
      sex did not survive after 7 d with access only to water. Moreover, starved
      females did not produce mature eggs. Thus, food consumption by adult D. balteata
      is very important to their survival and reproductive performance, and it is
      likely that females fed Valmaine failed to produce mature eggs because they did
      not consume a sufficient amount of this cultivar. However, because Valmaine-fed
      beetles maintained their body weight and lived significantly longer than starved
      beetles, it appears that they can obtain some nourishment from their limited
      feeding on this cultivar. Overall, these results suggest that Valmaine, and to a
      lesser extent short Guzmaine (a cultivar produced by crossing Valmaine with two
      other cultivars), exhibit antixenosis-based resistance against D. balteata.

PMID- 12216829
TI  - High nucleotide diversity in the para-like voltage-sensitive sodium channel gene
      sequence in the western flower thrips (Thysanoptera: Thripidae).
AB  - In a search for a pyrethroid resistance diagnostic marker, a partial sequence of
      the para-like sodium channel gene was obtained from 78 diploid females of the
      arrhenotokous insect pest species Frankliniella occidentalis (Pergande), the
      western flower thrips. Although all the insects analyzed came from a single
      laboratory population, nine different haplotypes were obtained. Two haplotypes
      did have the well-known L to F kdr mutation, but only one of these could be
      statistically linked to pyrethroid resistance in our population. This haplotype
      did not have the superkdr mutation, but did have a unique mutation a few amino
      acids downstream, at a position already linked to resistance in Plutella.
      Although this para-like locus seemed to have a role in pyrethroid resistance in
      our population, other resistance mechanisms were also probably involved. The fact
      that our laboratory population, open to migration, contained ahigh genetic
      diversity forthis selected gene shows that "pest tourism" is a major factor for
      resistance dynamics in this greenhouse pest. This, with the possible occurrence
      of an original resistance mutation, might preclude the use of very specific
      approaches for resistance monitoring in the field in this species.

PMID- 12216831
TI  - Sampling methods as abundance indices for adult Diaprepes abbreviatus
      (Coleoptera: Curculionidae) in citrus.
AB  - Beat sampling and two type of traps, cup traps and Tedders traps, were evaluated
      as sampling methods to detect and estimate population densities of adult
      Diaprepes abbreviatus L. weevils newly colonizing young citrus trees. The study
      was conducted over a 65-wk period across a 0.25-ha area of 80 citrus trees
      [Citrus sinensis (L.) Osbeck] (1.2-1.5 m tall). Beat samples were taken weekly to
      determine the number of trees infested and number of new adult weevils per tree.
      Sixteen of the 80 trees studied were each monitored weekly using one of the
      following trapping methods: cup traps in trees, cup traps on a stake in the
      ground within the tree drip line, cup traps on a stake in the ground outside of
      the drip line, Tedders traps on the ground within the drip line, and Tedders
      traps on the ground outside of the drip line. Weevils collected each week from
      trees and traps were removed from the study site. Based on the coefficients
      associated with Taylor's power law, the optimum numbers of trees to sample for an
      SEM equal to 25% of the mean estimate decreased from 50 trees at a mean of 0.5
      new weevils per tree to 30 trees at a mean of 0.8 new weevils per tree. A
      significant relationship was found between the weekly mean number of new weevils
      per tree and the proportion of trees infested, a binomial relationship that could
      be further explored in the search for a sampling program for adult D.
      abbreviatus. Regression analyses indicated that three of the trapping methods
      served at least as weak indices of the presence and abundance of new weevils: cup
      traps in trees, Tedders traps inside the dripline and Tedders traps outside the
      dripline. Cup traps in trees and Tedders traps inside the dripline captured the
      most weevils and most frequently detected weevils. Although relatively
      inefficient as abundance indices of populations of new weevils, these two
      trapping methods appeared to have some value with respect to signaling when
      weevils first appeared in trees during the spring.

PMID- 12216832
TI  - Genetics of resistance to phosphine in Rhyzopertha dominica (Coleoptera:
      Bostrichidae).
AB  - The inheritance of resistance to phosphine was studied in two strains of the
      lesser grain borer, Rhyzopertha dominica (F.), labeled 'Weak-R' and 'Strong-R'.
      These strains were purified versions of field-selected populations collected in
      Queensland, Australia. Weak-R and Strong-R were, respectively, 23.4 times (20-h
      exposure) and 600 times (48-h exposure) resistant to phosphine compared with a
      reference susceptible strain (S-strain). Each -R strain was crossed with the S
      strain and the response to phosphine was measured in their respective F1, F2, and
      F1-backcross (F1-BC) progenies. Data from testing of reciprocal F1 progeny
      indicated that resistance in Weak-R was autosomal and incompletely recessive with
      a degree of dominance -0.96. Modified chi-square analysis and contingency
      analysis of the observed response to phosphine of F1-BC and F2 progenies rejected
      the hypothesis of single gene inheritance of resistance. Analysis of the response
      of the F1, F2, and F1-BC progeny from the Strong-R x S-strain cross also rejected
      the null hypothesis for single gene resistance. Resistance in the Strong-R strain
      was autosomal and incompletely recessive with a degree of dominance of -0.64. The
      Weak-R and Strong-R strains were then crossed. Analysis ofthe F1 and F2 progenies
      of this reciprocal cross revealed that the strong resistance phenotype was coded
      by a combination of the genes already present in the Weak-R genotype plus an
      extra major, incompletely recessive gene. There was also evidence of a minor
      dominant gene present in approximately 5% of Strong-R individuals.

PMID- 12216833
TI  - Action of 1-(11-selenadodecyl)-glycerol and 1-(11-selenadodecyl)-3-trolox
      glycerol against lipid peroxidation.
AB  - The antioxidant action on lipid peroxidation of the synthesized selenium
      compounds 1-(11-selenadodecyl)-glycerol (SeG) and 1-(11-selenadodecyl)-3-Trolox
      glycerol (SeTrG, where Trolox = 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic
      acid) was investigated. We compared the reactivity of the selenium compounds
      toward peroxyl radicals and their inhibitory effect on lipid peroxidation,
      induced by several kinds of initiating species such as azo compounds, metal ions,
      and superoxide/nitric oxide in solution, micelles, membranes, and rat plasma.
      SeTrG, but not SeG, scavenged peroxyl radicals. SeG reduced methyl linoleate
      hydroperoxides in organic solution and in methyl linoleate micelles oxidized by
      ferrous ion (Fe2+)/ascorbic acid. In rat plasma SeG and SeTrG decreased the
      formation of lipid hydroperoxides generated by hydrophilic azo compounds. SeG and
      SeTrG spared alpha-tocopherol (alpha-TOH) consumption in multilamellar vesicle
      membranes oxidized by hydrophilic or lipophilic initiators, and only SeTrG spared
      alpha-TOH in superoxide/nitric oxide oxidized membranes. In rat plasma oxidized
      by radical initiators (either hydrophilic or lipophilic) or superoxide/nitric
      oxide, SeTrG suppressed alpha-TOH consumption, but SeG had no effect. The two
      selenium-containing compounds showed inhibitory effects on lipid peroxidation
      that depended on their structure, the medium where they acted, and the oxidant
      used.

PMID- 12216834
TI  - Interaction of CETP inhibitory peptide and lipoprotein substrates in cholesteryl
      ester transfer assay: relationship between association properties and inhibitory
      activities.
AB  - In a previous study, CETP inhibitory peptide (3 kDa) was isolated from hog
      plasma. The peptide, synthesized chemically according to the amino acid sequence
      of the 3-kDa peptide (designated P28), showed CETP inhibitory activity both in
      vitro and in vivo ICho et al. (1998) Biochim. Biophys. Acta 1391, 133-144]. We
      report herein further unique features of P28 when it was associated with the
      cholesteryl ester (CE)-donor and -acceptor lipoproteins. Lipoprotein substrates
      with P28 present in both HDL (as a CE-donor) and LDL (as a CE-acceptor) served as
      poor substrates, with CE-transfer activity decreased up to 60% compared to normal
      substrates without P28. P28 was found to be located in HDL fractions of hog
      plasma and showed the same electromobility as that visualized by PAGE on 7%
      polyacrylamide gel under nondenaturing conditions. Addition of apolipoprotein A-1
      (apoA-1) or apoB antibody to a normal CE-transfer mixture did not alter CE
      transfer activity. However, addition of apoA-1 or -B antibody to a CETP
      inhibition mixture decreased the inhibitory activity of P28 by ca. 20%. Western
      blot analysis revealed that P28 was associated only with human and hog HDL among
      several lipoproteins purified from human, hog, and rabbit. CETP-inhibition assays
      with various lipoprotein substrates revealed that P28 exhibited substrate
      specific inhibitory activity. The inhibitory activity of P28 was highly dependent
      on the type of lipoprotein substrate (whether CE-donor or -acceptor); P28
      inhibited CE transfer from HDL to LDL, but it did not inhibit CE transfer from
      HDL to HDL.

PMID- 12216835
TI  - Intestinal apolipoprotein B secretion is inhibited by the flavonoid quercetin:
      potential role of microsomal triglyceride transfer protein and diacylglycerol
      acyltransferase.
AB  - Recent studies have yielded evidence that plant flavonoids reduce hepatic lipid
      and apolipoprotein B (apoB) secretion. However, the possible role of flavonoids
      in regulating lipid and apoB secretion by the intestine has not been studied. The
      purpose of our study was to examine the effects of quercetin, a common dietary
      flavonoid, on TAG and apoB secretion in a human intestinal cell-line, CaCo-2.
      Differentiated postconfluent CaCo-2 cells grown on filters and pretreated with
      quercetin for 8 h were shown by ELISA to inhibit basolateral apoB secretion in a
      dose-dependent manner. At 15 microM, the secretion of both apoB-100 and apoB-48
      were inhibited similarly. This effect was shown to be specific, as quercetin did
      not affect the incorporation of [35S]methionine/cysteine into secreted TCA
      precipitable proteins. To determine the mechanism underlying this inhibitory
      effect, we examined two regulatory points: TAG availability and lipid transfer to
      the lipoprotein particle. Quercetin inhibited TAG synthesis under both basal and
      lipid-rich conditions, indicating that lipid availability is a determining factor
      in the regulation of apoB secretion by quercetin. The reduction was due at least
      in part to a decrease in diacylglycerol acyltransferase activity. We next
      examined lipid transfer or lipidation of the lipoprotein particle by analyzing
      microsomal TAG transfer protein (MTP) activity. Quercetin decreased MTP activity
      moderately. In summary, the data demonstrated that pharmacological concentrations
      of quercetin are a potent inhibitor of intestinal apoB secretion and that reduced
      lipid availability and lipidation in the lipoprotein assembly step are the
      mechanism for the suppression of apoB-containing lipoprotein secretion by
      quercetin in CaCo-2 cells.

PMID- 12216836
TI  - Distinction between esterases and lipases: a kinetic study with vinyl esters and
      TAG.
AB  - The better to characterize enzymes hydrolyzing carboxyl ester bonds (carboxyl
      ester hydrolases), we have compared the kinetic behavior of various lipases and
      esterases against solutions and emulsions of vinyl esters and TAG. Short-chain
      vinyl esters are hydrolyzed at comparable rates by esterases and lipases and have
      higher limits of solubility in water than corresponding TAG. Therefore, they are
      suited to study the influence of the physical state of the substrate on carboxyl
      ester hydrolase activity within a large concentration range. Enzymes used in this
      study are TAG lipases from microorganisms, lipases from human and guinea pig
      pancreas, pig liver esterase, and acetylcholinesterase. This study also includes
      cutinase, a fungal enzyme that displays functional properties between esterases
      and lipases. Esterases display maximal activity against solutions of short-chain
      vinyl esters (vinyl acetate, vinyl propionate, and vinyl butyrate) and TAG
      (triacetin, tripropionin, and tributyrin). Half-maximal activity is reached at
      ester concentrations far below the solubility limit. The transition from solution
      to emulsion at substrate concentrations exceeding the solubility limit has no
      effect on esterase activity. Lipases are active on solutions of short-chain vinyl
      esters and TAG but, in contrast to esterases, they all display maximal activity
      against emulsified substrates and half-maximal activity is reached at substrate
      concentrations near the solubility limit of the esters. The kinetics of
      hydrolysis of soluble substrates by lipases are either hyperbolic or deviate from
      the Michaelis-Menten model and show no or weak interfacial activation. The
      presence of molecular aggregates in solutions of short-chain substrates, as
      evidenced by a spectral dye method, likely accounts for the activity of lipases
      against soluble esters. Unlike esterases, lipases hydrolyze emulsions of water
      insoluble medium- and long-chain vinyl esters and TAG such as vinyl laurate,
      trioctanoin, and olive oil. In conclusion, comparisons of the kinetic behavior of
      carboxyl ester hydrolases against solutions and emulsions of vinyl esters and TAG
      allows the distinction between lipases and esterases. In this respect, it clearly
      appears that guinea pig pancreatic lipase and cutinase are unambiguously
      classified as lipases.

PMID- 12216837
TI  - PC and PE synthesis: mixed micellar analysis of the cholinephosphotransferase and
      ethanolaminephosphotransferase activities of human choline/ethanolamine
      phosphotransferase 1 (CEPT1).
AB  - The human choline/ethanolamine phosphotransferase 1 (CEPT1) gene codes for a dual
      specificity enzyme that catalyzes the de novo synthesis of the two major
      phospholipids through the transfer of a phosphobase from CDP-choline or CDP
      ethanolamine to DAG to form PC and PE. We used an expression system devoid of
      endogenous cholinephosphotransferase and ethanolaminephosphotransferase
      activities to assess the diradylglycerol specificity of CEPT1. A mixed micellar
      assay was used to ensure that the diradylglycerols delivered were not affecting
      the membrane environment in which CEPT1 resides. The CEPT1 enzyme displayed an
      apparent Km of 36 microM for CDP-choline and 4.2 mol% for di-18:1 DAG with a Vmax
      of 14.3 nmol min(-1) mg(-1). When CDP-ethanolamine was used as substrate, the
      apparent Km was 98 microM for CDP-ethanolamine and 4.3 mol% for di-18:1 DAG with
      a Vmax of 8.2 nmol min(-1) mg(-1). The preferred diradylglycerol substrates used
      by CEPT1 with CDP-choline as the phosphobase donor were di-18:1 DAG, di-16:1 DAG,
      and 16:0/18:1 DAG. A major difference between previous emulsion-based assay
      results and the mixed micelle results was a complete inability to use 16:0(O)/2:0
      as a substrate for the de novo synthesis of platelet-activating factor when the
      mixed micelle assay was used. When CDP-ethanolamine was used as the phosphobase
      donor, 16:0/18:1 DAG, di-18:1 DAG, and di-16:1 DAG were the preferred substrates.
      The mixed micelle assay also allowed the lipid activation of CEPT to be measured,
      and both the cholinephosphotransferase and ethanolaminephosphotransferase
      activities displayed the unusual property of product activation at 5 mol%,
      implying that specific lipid activation binding sites exist on CEPT1. The protein
      kinase C inhibitor chelerythrine and the human DAG kinase inhibitor R59949 both
      inhibited CEPT1 activity with IC50 values of 40 microM.

PMID- 12216838
TI  - Effect of fenitrothion on the physical properties of crustacean lipoproteins.
AB  - The effect of the liposoluble organophosphorus insecticide fenitrothion (FS) on
      lipid packing and rotation of two crustacean plasma HDL was investigated. These
      lipoproteins, HDL-1 and HDL-2, differed in their lipid composition, but their
      lipid/protein ratios were similar. The rotational behavior of the fluorescent
      probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and 3-(p-(6-phenyl)-1,3,5-hexatrienyl)
      phenylpropionic acid (DPH-PA) was used to obtain information about the lipid
      dynamics in the outer and inner regions, respectively, of the lipid phase of the
      lipoproteins. Fluorescent steady-state anisotropy (r(s)), lifetime (tau),
      rotational correlation time (tau(r)), and the limiting anisotropy (r(infinity))
      of these probes were measured in the lipoproteins exposed to different
      concentrations of FS in vitro. The results showed the penetration of FS into both
      plasma lipoproteins, altering the lipid dynamics of the inner as well as the
      outer regions. The overall effect of the insecticide was to induce an increase in
      the lipid order in a concentration-dependent fashion. DPH and DPH-PA fluorescence
      lifetime shortening indicated that FS increased the polarity of the probe
      environment, suggesting an enhanced water penetration into the lipoprotein lipid
      phase, may be due to the induction of failures in the lipid packing. Even in the
      absence of FS, a higher ordering of the lipid phase was found in HDL-2 compared
      to HDL-1, a fact that might be attributed to a higher percentage of sphingomyelin
      in HDL-2.

PMID- 12216839
TI  - Trans-7,cis-9 CLA is synthesized endogenously by delta9-desaturase in dairy cows.
AB  - Cis-9,trans-11 and trans-7,cis-9 CLA are the most prevalent CLA isomers in
      milkfat. The majority of cis-9,trans-11 CLA is synthesized endogenously by delta9
      desaturase. We tested the hypothesis that trans-7,cis-9 CLA originates from
      endogenous synthesis by inhibiting delta9-desaturase with a source of
      cyclopropene FA (sterculic oil: SO) or with a trans-10,cis-12 CLA supplement.
      Experiment 1 (four cows; Latin square) involved four treatments: control, SO,
      partially hydrogenated vegetable oil (PHVO), and PHVO + SO. Milk, plasma, and
      rumen fluid were collected. Experiment 2 treatments (four cows) were 0 or 14.0
      g/d of 10,12 CLA supplement; milk and plasma were collected. Samples were
      analyzed by GC and Ag+-HPLC to determine FA. In Experiment 1, SO decreased
      milkfat content of trans-7,cis-9 CLA by 68 to 71% and cis-9,trans-11 CLA by 61 to
      65%. In Experiment 2, the 10,12 CLA supplement decreased milkfat content of trans
      7,cis-9 CLA and cis-9,trans-11 by 44 and 25%, respectively. Correcting for the
      extent of treatment-induced inhibition of delta9-desaturase based on changes in
      myristic and myristoleic acids, endogenous synthesis of trans-7,cis-9 CLA
      represented 85 and 102% in Experiments 1 and 2, respectively. Similar corrected
      values were 77 and 58% for endogenous synthesis of cis-9,trans-11 CLA. Thus,
      milkfat cis-9,trans-11 CLA was primarily from endogenous synthesis with a minor
      portion from rumen escape. In contrast, trans-7,cis-9 CLA was not present in
      rumen fluid in significant amounts. Results indicate this isomer in milkfat is
      derived almost exclusively from endogenous synthesis via delta9-desaturase.

PMID- 12216840
TI  - High intake, but not low intake, of CLA impairs weight gain in growing mice.
AB  - CLA has a range of biological properties, including effects on lipid metabolism
      and body composition in experimental animals. The prevalent isomer of CLA found
      in the human diet is 9c,11 t-CLA, and it is predominantly found in products
      containing fat from ruminant animals. This study investigated the effect of
      dietary CLA on energy balance in mice. Synthetic CLA reduced body fat in growing
      male BALB/c mice in a dose-dependent manner over the range 0.25-1.0% w/w CLA in
      the diet. Weight gain was also reduced at the highest levels of dietary CLA,
      being only 5.88 +/- 2.68 g/4 mice (mean +/- 1 SD) after 4 wk of 2.0% CLA in the
      diet, compared with weight gains of 7.51 +/- 2.22 to 8.17 +/- 2.34 g/4 mice in
      the 0-0.5% CLA groups. There was no significant effect on weight gain if diets
      contained 0.5% synthetic CLA or less. These results suggest that high levels of a
      synthetic mixture of CLA isomers modify energy metabolism and body composition
      and that high levels of synthetic CLA impair weight gain and reduce body fat pad
      mass in growing mice.

PMID- 12216841
TI  - Interaction between dietary protein and fat in triglyceride metabolism in the
      rat: effects of soy protein and menhaden oil.
AB  - The objective of the present study was to determine the mechanisms by which
      dietary proteins interact with dietary lipids in the regulation of
      triglyceridemia in rats. Male Sprague-Dawley rats (n = 56) were subjected to 28-d
      experimental diets containing different combinations of proteins (20% w/w) and
      lipid sources (14% w/w): (i) casein-menhaden oil, (ii) casein-beef tallow, (iii)
      soy protein-menhaden oil, and (iv) soy protein-beef tallow. Significant protein
      lipid interactions were observed on triglyceridemia and hepatic cholesterol in
      fasted rats. The combination of casein and beef tallow was associated with high
      plasma TG and hepatic cholesterol concentrations, which were reduced by
      substitution either of soy for casein or of menhaden oil for beef tallow.
      Therefore, triglyceridemia and liver cholesterol remained low with soy protein
      feeding, independently of the lipid source, as well as with menhaden oil feeding,
      regardless of the protein source. The menhaden oil diets reduced plasma
      cholesterol, hepatic TG, and TG secretion compared with beef tallow diets
      independently of the dietary protein source. Modifying the source of dietary
      proteins and lipids had no effect on post-heparin plasma lipoprotein lipase
      activity. These results demonstrate that soy protein can lower rat
      triglyceridemia relative to casein when associated with beef tallow consumption,
      whereas menhaden oil can attenuate hypertriglyceridemia when rats are fed casein.
      The data further suggest that part of the hypotriglyceridemic effect of soy
      protein in the rat may be mediated by reduced hepatic lipid synthesis, as is the
      case for menhaden oil.

PMID- 12216843
TI  - Positional and geometric isomer separation of FAME by comprehensive 2-D GC.
AB  - The technique of comprehensive GC (GC x GC) was applied to the analysis of a
      standard mixture of FAME. The methodology involved the use of two directly
      coupled capillary GC columns providing different retention mechanisms, with a
      pulsing modulator located near their union. The first column was chosen to elute
      analytes based on b.p. variations, and the second column was based on polarity.
      Thus, the separation in the two dimensions was orthogonal, since solutes
      delivered simultaneously to the second column had similar b.p., and the second
      column separated these primarily on their differentiating mechanisms of polarity.
      Greater sensitivity of detection and narrower peak widths were obtained; here,
      peak response increases of about 20-fold were obtained, with pulsed peak widths
      of about 150 ms. Peaks were displayed in a 2-D contour plot to allow the
      complexity of the compounds to be seen and their b.p. and polarity properties to
      be readily recognized. Chromatographic separation of geometric and positional
      isomers of FAME in the 2-D space is possible. Since retention can be related to
      the degree and manner of unsaturation and isomerization, and as peak positions
      are highly reproducible in the 2-D retention map, this is a useful aid for
      component identification in the absence of appropriate standards. In this work,
      two column combinations were used to examine the effects of polarity changes on
      component separation. Improved quantitation based on FID area measurement was
      demonstrated. A sample of marine oil gave 49 resolved, identified peaks, with at
      least an additional 20 peaks resolved but not identified.

PMID- 12216842
TI  - Correlation between fatty acyl composition in neutral and polar lipids and enzyme
      activities from various tissues of calcium-deficient rats.
AB  - In this study we investigated the changes induced by feeding rats a calcium
      deficient diet (0.5 g Ca/kg diet) during 65 d after weaning. Phospholipase A2,
      acyl-Co synthetase and FA delta9-, delta6-, and delta5-desaturase activities were
      also determined. Calcium deficiency evoked a general alteration in the quality
      and proportion of the FA chains acylated to neutral and polar lipids from liver,
      lungs, spleen, brain, kidneys, fat, articular cartilage, erythrocyte ghosts, and
      plasmas, characterized by an increment of saturated FA and a significant
      depletion of polyunsaturated acids derived from linoleate and alpha-linolenate.
      Several interlipid and lipid/protein relationships were also modified in
      microsomes from calcium-deprived rats, with a concomitant reduction in the
      rotational mobility of the probe diphenylhexatriene. Phospholipase A2 and acyl
      CoA synthetase activities were also decreased and increased, respectively, in
      some tissues from calcium-deficient rats, whereas delta9-, delta6- and delta5
      desaturases were significantly depressed. We conclude that changes in tissue
      fatty acyl composition evoked by calcium deprivation are due to alterations in
      the acylation/deacylation cycles via inhibition of the phospholipase A2. These
      changes were reflected in the physicochemical properties of the membranes, which
      in turn inhibits desaturase activities. A possible failure in the transcriptional
      rate for desaturase-mRNA was also discussed.

PMID- 12216844
TI  - Similar effects of c9,t11-CLA and t10,c12-CLA on immune cell functions in mice.
AB  - Published results regarding the effects of CLA on immune cell functions have
      ranged from stimulation to inhibition. In those studies, a mixture of CLA isomers
      were used, and food intake was not controlled. We have examined whether the
      discrepancies in the results of earlier studies may be due to the lack of
      controlled feeding and whether the two isomers of CLA may differ in their effects
      on immune cell functions. Three groups of C57BL/6 female mice were fed either a
      control, c9,t11-CLA-, or t10,c12-CLA (0.5 wt%)-supplemented diet, 5 g/d, for 56
      d. At the end of the study, the number of immune cells in spleens, bone marrows,
      or in circulation; proliferation of splenocytes in response to T and B cell
      mitogens; and prostaglandin secretion in vitro did not differ among the three
      groups. Both CLA isomers significantly increased in vitro tumor necrosis factor
      alpha and interleukin (IL)-6 secretion and decreased IL-4 secretion by
      splenocytes compared to those in the control group. Thus, the two CLA isomers had
      similar effects on all response variables tested. The discrepancies among the
      results from previous studies did not seem to be caused by the differences in the
      isomer composition of CLA used.

PMID- 12216845
TI  - Vascular access: a role for a renal nurse clinician.
AB  - The team approach to the delivery of healthcare is important and has become more
      so since the boundaries between professional groups have become blurred. Renal
      replacement therapy requires that patients have adequate access. This could be in
      the form of an arterio-venous fistula, a graft, or a vascular catheter. Doctors
      have historically always provided access for patients. Placement of vascular
      access is a lengthy process often causing long delays and anxiety. Due to the
      reduction in junior doctors hours and the further demands on senior medical
      staff, a nurse was nominated and developed the role of vascular access specialist
      and clinician. Before the development of the nurse clinicians' role, the
      situation in this centre regarding venous access for haemodialysis was based on
      an ad hoc arrangement between junior doctors. Historically surgeons and medical
      staff have always provided vascular access for haemodialysis. However, it was
      felt that a suitably educated renal nurse would be more suitable to develop this
      role, and a relevant course, (MSc in Advanced Nursing Practice) had been
      developed at a nearby university. The access role included the insertion of both
      short and long-term vascular access catheters. An access referral pathway is now
      in place, giving a streamlined service. A designated access specialist nurse now
      inserts vascular access, providing focused individualised care specifically
      targeted at the renal patients' needs. Because of the success of this role, four
      more nurses are being supported to undertake the clinical MSc. The aim is to
      develop other areas of renal provision and to provide a nurse led specialist
      individualised service in line with the future National Service Framework. The
      role has also provided scope for nursing career development, giving motivation to
      experienced clinical nurses who wish to remain clinically involved, improve the
      care for patients and progress their career.

PMID- 12216846
TI  - The renal diabetic nurse specialist...a luxury or an essential player?
AB  - Diabetic Nephropathy is the single largest cause of Chronic Renal Failure. As the
      number of patients referred to a nephrologist increase, the needs of many
      diabetic nephropaths are not being met. The post of Renal Diabetes Nurse
      Specialist (DNS) was instituted in September 1999 to organise the management of
      and to meet all aspects of need of this group of patients. The role currently
      incorporates a daily ward round with the aim of reviewing all patients at least
      once during every admission to hospital. Ward-based teaching with the patients
      occurs and six nurse-led clinics covering all modalities are now in place and run
      alongside the Nephrologist. Patients are either referred directly to the nurse
      led clinic or are approached by the renal DNS whilst the patient is in the
      nephrology clinic. 71.4% of our diabetic patients have an improvement in their
      HbA1c after 21 months of working closely with the Renal DNS and multidisciplinary
      team. The average HbA1c at the beginning was 9.7%; the average is now 8%. It is
      clear that the role is being continuously stretched to its absolute limit. Our
      aim is to develop a broader service over time and we will, in the near future be
      employing a renal nurse with an interest in diabetes to work alongside the DNS
      for six months to particularly learn about the needs of our in-patients.

PMID- 12216847
TI  - Self adhesive dressing pouch for the protection of catheters.
AB  - This paper is about a new model of dressing, used for the protection of all types
      of temporary and permanent catheters. Those who developed this dressing realised
      the practical difficulties during the placement and removal of traditional
      dressings, used in haemodialysis units. They also realised that it this was
      unpleasant for the patients, and there was a risk to the catheters when removing
      the dressings because of the use of scissors and other cutting instruments. This
      new dressing solves these previously mentioned problems and at the same time
      contributes to the comfort of the patients. The model has been registered as a
      standard using model, and therefore it is protected by law and its copyright
      (Intellectual Property).

PMID- 12216848
TI  - The SF-36: an instrument for measuring quality of life in ESRD patients.
AB  - This paper provides a review of four studies, which use the generic Medical
      Outcome Study Questionnaire 36-Item Short Form Survey (SF-36) to investigate the
      quality of life of patients with end-stage renal disease. Both English and
      translated versions of this instrument have been demonstrated to be valid. It is
      difficult however, to compare results from western and eastern populations as
      cultural differences may influence how people rate their quality of life. The SF
      36 has been demonstrated to be a valid instrument when used to measure the
      quality of life of ESRD patients. Research findings from Europe and the United
      Kingdom demonstrate that patients who are treated with a successful renal
      transplant can experience a QOL which, is superior to that achieved with any
      dialysis modality and which is very close to the QOL scores of the general
      population. It is acknowledged that while the studies cited in this article all
      used the SF-36 the research design employed in each instance is not exactly
      comparable, and any conclusions drawn here require further testing.

PMID- 12216849
TI  - N = the sample size: please handle with respect!

PMID- 12216850
TI  - A practical approach to the molecular biology of kidney diseases: from basic
      science to bed side.
AB  - Nowadays, the term "Molecular Biology" (MB) is generally a pplied to the
      biochemical processes that involve genes and the expression of proteins for which
      specific genes code. In recent years, astonishing advances have occurred in this
      field. Currently, there are many important powerful techniques allowing
      scientists to study the molecular mechanisms involved in many human genetic
      diseases. Furthermore, it is important to underline that the possibilities are
      not limited to the diagnosis and study of these genetic diseases. Indeed, by
      studying gene expression, MB also allows the molecular study of many acquired
      diseases such as viral hepatitis and cancer.Therefore, these major advances in
      the knowledge of gene biology are facilitating the arrival of a new era of gene
      therapy. This article will describe the most important techniques currently used
      in MB. Firstly, techniques involved in recombinant DNA technology will be
      discussed and these will include the study of DNA and the possibility of
      identifying the expression of abnormal genes, e.g. to identify individuals for
      paternity. Secondly, a description of techniques designed to study the expression
      of genes and their regulation will follow and they involve the study of RNA.
      Thirdly, the impact of genetic molecular studies as tools for medical diagnosis
      will be discussed and analysed. Finally, a discussion concerning the rational
      basis for gene therapy and its future perspectives is included. In this article,
      we have focused on technical or diagnostic aspects ofMolecular Biology. Although
      Ethics are also an interesting issue to deal with, theseissues are far beyond the
      scope of this review.

PMID- 12216851
TI  - Unstable diabetes and peritoneal dialysis--what are the challenges?
AB  - This case study outlines the care of a young woman undergoing peritoneal dialysis
      (PD) who has Type 1 diabetes mellitus as the underlying cause of her renal
      disease. Although she is able to manage the practical aspects of her fluid
      exchanges and exit-site care, she has difficulty with managing her fluid balance.
      This necessitates the use of two 3.86% glucose bags per day, which in turn
      sometimes leads to high, unstable, blood glucose levels. This study will outline
      the nursing challenges and interventions and will evaluate the nursing
      management.

PMID- 12216852
TI  - Management of a pregnant woman dependent on haemodialysis.
AB  - This is a case study of a woman who became pregnant whilst receiving
      haemodialysis in a London teaching hospital. She courageously disregarded the
      doctors' advise to abort the fetus. The doctors advised her to wait until she had
      a kidney transplant to become pregnant again, rather than increase maternal and
      fetal risk on dialysis. She was due to have a live-related transplant from her
      father in the spring. The case study describes a practical account in detailed
      measure to equip nurses with the knowledge to provide specialised care to high
      risk dialysis expecting mothers. The main problems in this case study were trying
      to manage the mother's dialysis regime, control her anaemia, ensure good
      nutritional levels and gain accurate daily weights.

PMID- 12216853
TI  - Patient-centred care in Turkey.

PMID- 12216854
TI  - Permanent indwelling catheters, a potentially dangerous approach to vascular
      access.

PMID- 12216855
TI  - A modest approach to the suffering of renal patients.

PMID- 12216856
TI  - Cycads: their evolution, toxins, herbivores and insect pollinators.
AB  - Palaeobiological evidence indicates that gymnosperms were wind-pollinated and
      that insect pollination began in angiosperms in the Lower Cretaceous (ca. 135
      mya) leading to close associations between higher plants and their pollinators.
      Cycads, which were widespread and pervasive throughout the Mesozoic (250-65 mya)
      are among the most primitive living seed-plants found today. Because pollination
      by beetles and by thrips has now been detected in several modern cycads, it is
      attractive to speculate that some insects and cycads had already developed
      similar mutualistic interactions in the Triassic (250-205 mya), long before the
      advent of angiosperms. We also draw attention to another key factor in this
      insect-plant relationship, namely secondary, defensive plant substances which
      must always have controlled interspecific interactions. Cycads mainly produce
      toxic azoglucosides and neurotoxic non-protein amino acids (e.g. BMAA), which
      apparently are crucial elements in the development and maintenance of mutualism
      (pollination) and parasitism (herbivory) by cycad-linked herbivores. We now add
      new results on the uptake and storage of the main toxin, cycasin, of the Mexican
      cycad Zamia furfuracea by its pollinator, the weevil Rhopalotria mollis, and by a
      specialist herbivore of Zamia integrifolia, the aposematic Atala butterfly
      Eumaeus atala.

PMID- 12216857
TI  - The origin of extensive colour polymorphism in Plateumaris sericea
      (Chrysomelidae, Coleoptera).
AB  - Evidence is presented to demonstrate that colour polymorphism in a beetle arises
      from structural colours produced by a five-layered reflector in the elytron. The
      colour of leaf beetles, Plateumaris sericea, ranges across the visible spectrum
      from blackish-blue to red. The elytra have two distinct layers: epicuticle and
      exocuticle. Morphological observations reveal that the multilayer structure
      within the exocuticle differs little among the different colour morphs but the
      layers within the epicuticle have characteristic thicknesses corresponding to the
      observed colour. The reflectors, consisting of five layers within the epicuticle,
      are responsible for all the different colours observed in P. sericea, as shown by
      theoretical analyses for a multilayer stack, and by showing that removal of the
      elytral surface, including epicuticle, results in the disappearance of the
      iridescent colour.

PMID- 12216858
TI  - Hot spots in the bee hive.
AB  - Honeybee colonies (Apis mellifera) maintain temperatures of 35-36 degrees C in
      their brood nest because the brood needs high and constant temperature conditions
      for optimal development. We show that incubation of the brood at the level of
      individual honeybees is done by worker bees performing a particular and not yet
      specified behaviour: such bees raise the brood temperature by pressing their warm
      thoraces firmly onto caps under which the pupae develop. The bees stay motionless
      in a characteristic posture and have significantly higher thoracic temperatures
      than bees not assuming this posture in the brood area. The surface of the brood
      caps against which warm bees had pressed their thorax were up to 3.2 degrees C
      warmer than the surrounding area, confirming that effective thermal transfer had
      taken place.

PMID- 12216859
TI  - A queen pheromone induces workers to kill sexual larvae in colonies of the red
      imported fire ant (Solenopsis invicta).
AB  - We conducted five bioassays to study how queens control the execution of sexual
      larvae by workers in colonies of the red imported fire ant, Solenopsis invicta.
      In each assay, subset colonies were made from many large polygyne colonies, and
      the 20 sexual larvae they contained were monitored over time. Sexual larvae
      mostly survived in queenless colonies, but were mostly killed in colonies with a
      single dealated queen, regardless of whether or not the queen was fertilized. The
      larvae were also killed when fresh corpses of queens were added to queenless
      colonies. Whereas acetone extracts of queens did not produce a significant
      increase in killings, extracts in buffered saline induced workers to execute most
      sexual larvae, indicating successful extraction of an execution pheromone. We
      identified the probable storage location of the chemical as the poison sac, and
      found both fresh (1 day) and old (21 day) extracts of poison sacs to be equally
      effective in inducing executions. The pheromone is stable at room temperature,
      perhaps because venom alkaloids also present in the extracts keep the pheromone
      from degrading. It is apparently either proteinaceous or associated with a
      proteinaceous molecule, a novel finding, as no queen pheromone of a proteinaceous
      nature has been previously demonstrated in ants.

PMID- 12216860
TI  - Gamergates in the myrmicine genus Metapone (Hymenoptera: Formicidae).
AB  - Gamergates (i.e. mated reproductive workers) are mostly known from ant species
      within the Ponerinae. We report here the discovery of gamergates in two species
      of the subfamily Myrmicinae. Until now, mated reproductive females in colonies of
      myrmicine species have been considered morphologically distinct from the worker
      caste. However, in two species of the myrmicine Metapone (Metapone madagascarica
      and a newly discovered, not yet described Metapone species) all workers have six
      ovarioles and a spermatheca; and some of them are mated. There are no
      morphological differences between mated and non-mated workers. Field observations
      and laboratory studies indicate that colonies of the Metapone species can
      reproduce with gamergates only.

PMID- 12216861
TI  - 2-Nitroethenylbenzenes as natural products in millipede defense secretions.
AB  - The white millipede Eucondylodesmus elegans Miyosi (Polydesmida: Doratodesmidae)
      secretes odoriferous droplets from the glands on both lateral surfaces of its
      body segments. The secretion was shown to be composed of a mixture of (1E)- and
      (1Z)-2-nitroethenylbenzenes (2-3 microg per millipede), identified by GC/MS
      analyses and synthesis. This is the first identification of these compounds as
      natural products. A granulated sugar block baited with the synthetic compound
      (more than 0.71 microg) demonstrated repellent activity against foraging wild
      ants, indicating that the compound functioned as a defense substance against
      potential predators. alpha,beta,2,3,4,5,6-d7-(1E)-2-Nitroethenylbenzene was
      detected by GC/MS analysis in the millipede secretion after feeding with
      alpha,beta,beta,2,3,4,5,6-d8-L-phenylalanine, indicating that L-phenylalanine is
      the precursor of these compounds.

PMID- 12216862
TI  - Attraction of the tropical bont tick, Amblyomma variegatum, to human breath and
      to the breath components acetone, NO and CO2.
AB  - Ticks are of medical and veterinary importance and employ several cues in search
      of a host. Olfaction is one modality by which ticks locate a blood-meal and
      breath is the major vent of gaseous and volatile metabolites from the host that
      could contribute to this search. We studied the responses of a hunter tick,
      Amblyomma variegatum, to diluted human breath and five of its components
      (acetone, CO2, NO, isoprene and NH3) while walking in an air stream on a
      locomotion compensator. Diluted breath elicited the greatest responses of all
      treatments in terms of time to onset of upwind walk, attraction, speed and local
      search behaviour after stimulus off. Acetone, NO and CO2 also attracted, but with
      a reduced speed in the case of acetone and NO. Neither isoprene nor NH3 induced
      any response. Our study indicates that breath was the most adequate stimulus
      tested. It also attracted two other ixodid tick species, Rhipicephalus sanguineus
      and Ixodes ricinus, as well as the argasid tick, Ornithodorus moubata. It appears
      that the evolution of resource tracking in ticks included sensory and behavioural
      adaptations for recognition and orientation to host metabolites that are
      regularly expelled in breath.

PMID- 12216863
TI  - Inter-cellular spike coincidences in visual detection tasks.
AB  - Synchronized spike activity is discussed as a possible representational code for
      object integration and as a neuronal basis of attention, perception and
      awareness. As a byproduct of experiments in which monkeys were trained to detect
      simple figures composed of single Gabor patches in a noisy background of similar
      elements, we found in special cases increased spike synchrony above chance level
      specifically related to figure detection. The long latency of this effect is
      difficult to interpret. It may be a sign of the cognitive state of an animal when
      it perceives the figure.

PMID- 12216864
TI  - Plant development in the absence of epiphytic microorganisms.
AB  - Microorganisms (bacteria, fungi) are common residents of the roots, stems and
      leaves of higher plants. In order to explore the dependency of plant development
      on the presence of epiphytic microorganisms, the achenes (seeds) of sunflower
      (Helianthus annuus L.) were sterilized and germinated under aseptic conditions.
      The sterility of the seedlings was determined with the agar impression method. In
      seedlings from non-sterile seeds (control) that were likewise raised in a germ
      free environment, all plant organs investigated (stem, cotyledons and primary
      leaves) were contaminated with bacteria. Hypocotyl elongation was not affected by
      epiphytic microorganisms. However, the growth rates of the cotyledons and primary
      leaves were higher in sterile seedlings compared with the control. The
      implications of this differential inhibition of organ development by epiphytic
      bacteria that are transmitted via the outer surface of the seed coat are
      discussed. We conclude that epiphytes in the above-ground phytosphere are not
      necessary for the development of the sunflower seedling.

PMID- 12216865
TI  - Foraging reactivation in the honeybee Apis mellifera L.: factors affecting the
      return to known nectar sources.
AB  - This paper addresses, what determines that experienced forager honeybees return
      to places where they have previously exploited nectar. Although there was already
      some evidence that dance and trophallaxis can cause bees to return to feed, the
      fraction of unemployed foragers that follow dance or receive food from employed
      foragers before revisiting the feeder was unknown. We found that 27% of the
      experienced foragers had no contact with the returning foragers inside the hive.
      The most common interactions were dance following (64%) and trophallaxis (21%).
      The great variability found in the amount of interactions suggests that
      individual bees require different stimulation before changing to the foraging
      mode. This broad disparity negatively correlated with the number of days after
      marking at the feeder, a variable that is closely related to the foraging
      experience, suggesting that a temporal variable might affect the decision-making
      in reactivated foragers.

PMID- 12216867
TI  - An algebraic algorithm for nonuniformity correction in focal-plane arrays.
AB  - A scene-based algorithm is developed to compensate for bias nonuniformity in
      focal-plane arrays. Nonuniformity can be extremely problematic, especially for
      mid- to far-infrared imaging systems. The technique is based on use of estimates
      of interframe subpixel shifts in an image sequence, in conjunction with a linear
      interpolation model for the motion, to extract information on the bias
      nonuniformity algebraically. The performance of the proposed algorithm is
      analyzed by using real infrared and simulated data. One advantage of this
      technique is its simplicity; it requires relatively few frames to generate an
      effective correction matrix, thereby permitting the execution of frequent on-the
      fly nonuniformity correction as drift occurs. Additionally, the performance is
      shown to exhibit considerable robustness with respect to lack of the common types
      of temporal and spatial irradiance diversity that are typically required by
      statistical scene-based nonuniformity correction techniques.

PMID- 12216866
TI  - Small hive beetles survive in honeybee prisons by behavioural mimicry.
AB  - We report the results of a simple experiment to determine whether honeybees feed
      their small hive beetle nest parasites. Honeybees incarcerate the beetles in
      cells constructed of plant resins and continually guard them. The longevity of
      incarcerated beetles greatly exceeds their metabolic reserves. We show that
      survival of small hive beetles derives from behavioural mimicry by which the
      beetles induce the bees to feed them trophallactically. Electronic supplementary
      material to this paper can be obtained by using the Springer LINK server located
      at htpp://dx.doi.org/10.1007/s00114-002-0326-y.

PMID- 12216868
TI  - Image description with Chebyshev-Fourier moments.
AB  - Chebyshev-Fourier moments for describing images were proposed. After definition
      of the moments, the multidistortion invariance of the moments was verified. The
      performance of the moments in describing images was investigated in terms of the
      normalized image-reconstruction error and the results of the experiments on the
      noise sensitivity are given.

PMID- 12216869
TI  - Object recognition using three-dimensional optical quasi-correlation.
AB  - A novel method of three-dimensional (3-D) object recognition is proposed. Several
      projections of a 3-D target are recorded under white-light illumination and fused
      into a single complex two-dimensional function. After proper filtering, the
      resulting function is coded into a computer-generated hologram. When this
      hologram is coherently illuminated, a correlation space is reconstructed such
      that light peaks indicate the existence and locations of true targets in the
      observed 3-D scene. Experimental results and comparisons with results of another
      3-D object recognition technique are presented.

PMID- 12216870
TI  - Wigner distribution moments in fractional Fourier transform systems.
AB  - It is shown how all global Wigner distribution moments of arbitrary order in the
      output plane of a (generally anamorphic) two-dimensional fractional Fourier
      transform system can be expressed in terms of the moments in the input plane.
      Since Wigner distribution moments are identical to derivatives of the ambiguity
      function at the origin, a similar relation holds for these derivatives. The
      general input-output relationship is then broken down into a number of rotation
      type input-output relationships between certain combinations of moments. It is
      shown how the Wigner distribution moments (or ambiguity function derivatives) can
      be measured as intensity moments in the output planes of a set of appropriate
      fractional Fourier transform systems and thus be derived from the corresponding
      fractional power spectra. The minimum number of (anamorphic) fractional power
      spectra that are needed for the determination of these moments is derived. As an
      important by-product we get a number of moment combinations that are invariant
      under (anamorphic) fractional Fourier transformation.

PMID- 12216871
TI  - Changes in modulation transfer function and optical resolution in helical
      turbulent media.
AB  - We study the change in the behavior of the modulation transfer function and
      resolution with changing properties of a turbulent medium. It is shown that the
      form and the behavior of the functions under study undergo significant changes at
      the transition from Kolmogorov's to a helical type of turbulent medium. These
      changes should be taken into account in developing models of electromagnetic
      radiation propagation through a medium as well as in interpreting experimental
      data.

PMID- 12216872
TI  - Optimal control of laser beams for propagation through a turbulent medium.
AB  - Concerning the problem of transmitting a laser beam from one telescope to another
      telescope through a turbulent medium, it is established that using an adaptive
      optical system on both telescopes to precompensate an outgoing laser beam based
      on the aberrations measured on the received laser beam leads to an iteration that
      maximizes the transmission (neglecting attenuation losses) of laser power between
      the telescopes. Simulation results are presented demonstrating the effectiveness
      of this technique when the telescopes are equipped with either phase-only or full
      wave compensation systems. Simulation results are shown that indicate that for a
      uniform distribution of the strength of turbulence, 95% transmission of laser
      power is attained when both telescopes can achieve full-wave compensation
      provided that the aperture diameter D of the two telescopes is greater than twice
      the Fresnel length square root of lambdaL, where A is the wavelength of
      propagation and L is the distance between the two telescopes.

PMID- 12216873
TI  - Atmospheric turbulence effects on a partially coherent Gaussian beam:
      implications for free-space laser communication.
AB  - A partially coherent quasi-monochromatic Gaussian laser beam propagating in
      atmospheric turbulence is examined by using a derived analytic expression for the
      cross-spectral density function. Expressions for average intensity, beam size,
      phase front radius of curvature, and wave-front coherence length are obtained
      from the cross-spectral density function. These results provide a model for a
      free-space laser transmitter with a phase diffuser used to reduce pointing
      errors.

PMID- 12216874
TI  - Efficient computation of minimum-variance wave-front reconstructors with sparse
      matrix techniques.
AB  - The complexity of computing conventional matrix multiply wave-front
      reconstructors scales as O(n3) for most adaptive optical (AO) systems, where n is
      the number of deformable mirror (DM) actuators. This is impractical for proposed
      systems with extremely large n. It is known that sparse matrix methods improve
      this scaling for least-squares reconstructors, but sparse techniques are not
      immediately applicable to the minimum-variance reconstructors now favored for
      multiconjugate adaptive optical (MCAO) systems with multiple wave-front sensors
      (WFSs) and DMs. Complications arise from the nonsparse statistics of atmospheric
      turbulence, and the global tip/tilt WFS measurement errors associated with laser
      guide star (LGS) position uncertainty. A description is given of how sparse
      matrix methods can still be applied by use of a sparse approximation for
      turbulence statistics and by recognizing that the nonsparse matrix terms arising
      from LGS position uncertainty are low-rank adjustments that can be evaluated by
      using the matrix inversion lemma. Sample numerical results for AO and MCAO
      systems illustrate that the approximation made to turbulence statistics has
      negligible effect on estimation accuracy, the time to compute the sparse minimum
      variance reconstructor for a conventional natural guide star AO system scales as
      O(n3/2) and is only a few seconds for n = 3500, and sparse techniques reduce the
      reconstructor computations by a factor of 8 for sample MCAO systems with 2417 DM
      actuators and 4280 WFS subapertures. With extrapolation to 9700 actuators and
      17,120 subapertures, a reduction by a factor of approximately 30 or 40 to 1 is
      predicted.

PMID- 12216875
TI  - Multigrid preconditioned conjugate-gradient method for large-scale wave-front
      reconstruction.
AB  - We introduce a multigrid preconditioned conjugate-gradient (MGCG) iterative
      scheme for computing open-loop wave-front reconstructors for extreme adaptive
      optics systems. We present numerical simulations for a 17-m class telescope with
      n = 48756 sensor measurement grid points within the aperture, which indicate that
      our MGCG method has a rapid convergence rate for a wide range of subaperture
      average slope measurement signal-to-noise ratios. The total computational cost is
      of order n log n. Hence our scheme provides for fast wave-front simulation and
      control in large-scale adaptive optics systems.

PMID- 12216876
TI  - Fluorescence spectral imaging for characterization of tissue based on
      multivariate statistical analysis.
AB  - A novel spectral imaging method for the classification of light-induced
      autofluorescence spectra based on principal component analysis (PCA), a
      multivariate statistical analysis technique commonly used for studying the
      statistical characteristics of spectral data, is proposed and investigated. A set
      of optical spectral filters related to the diagnostically relevant principal
      components is proposed to process autofluorescence signals optically and generate
      principal component score images of the examined tissue simultaneously. A
      diagnostic image is then formed on the basis of an algorithm that relates the
      principal component scores to tissue pathology. With autofluorescence spectral
      data collected from nasopharyngeal tissue in vivo, a set of principal component
      filters was designed to process the autofluorescence signal, and the PCA-based
      diagnostic algorithms were developed to classify the spectral signal. Simulation
      results demonstrate that the proposed spectral imaging system can differentiate
      carcinoma lesions from normal tissue with a sensitivity of 95% and specificity of
      93%. The optimal design of principal filters and the optimal selection of PCA
      based algorithms were investigated to improve the diagnostic accuracy. The
      robustness of the spectral imaging method against noise in the autofluorescence
      signal was studied as well.

PMID- 12216877
TI  - Propagation and focusing of Gaussian beams generated by Gaussian mirror
      resonators.
AB  - The propagation and focusing properties of a class of Gaussian beams generated by
      optical resonators with Gaussian reflectivity mirrors are investigated. Attention
      is concentrated on the following two beams in this class: (a) the annular
      Gaussian beam (the Gaussian doughnut mode) and (b) the flat-topped Gaussian beam.
      A class of flat-topped Gaussian beams is introduced. All analysis is limited to a
      coherent superposition scheme of the lowest-order Gaussian modes (TEM00) that
      have different parameters.

PMID- 12216878
TI  - Optical fiber Bragg gratings. Part I. Modeling of infinitely long gratings.
AB  - We present an accurate numerical method based on the Floquet-Bloch formalism to
      analyze the propagation properties and the radiation loss in infinitely long
      uniform fiber Bragg gratings. The model allows us to find all the propagation
      characteristics including the propagation constants, the space harmonics and the
      total field distribution, the guided and radiated power, and the modal loss
      induced by the periodic structure. The influence of the geometrical and physical
      parameters on the performance of the Bragg gratings has been established. A clear
      explanation of the physical phenomena related to the index modulation amplitude
      changes is presented, including the photonic bandgap effect, which is not easily
      described by the finite-difference time-domain method and cannot be described by
      the widely used coupled-mode theory.

PMID- 12216879
TI  - Optical fiber Bragg gratings. Part II. Modeling of finite-length gratings and
      grating arrays.
AB  - A model of both uniform finite-length optical fiber Bragg gratings and grating
      arrays is presented. The model is based on the Floquet-Bloch formalism and allows
      rigorous investigation of all the physical aspects in either single- or multiple
      periodic structures realized on the core of a monomodal fiber. Analytical
      expressions of reflectivity and transmittivity for both single gratings and
      grating arrays are derived. The influence of the grating length and the index
      modulation amplitude on the reflected and transmitted optical power for both
      sinusoidal and rectangular profiles is evaluated. Good agreement between our
      method and the well-known coupled-mode theory (CMT) approach has been observed
      for both single gratings and grating arrays only in the case of weak index
      perturbation. Significant discrepancies exist there in cases of strong index
      contrast because of the increasing approximation of the CMT approach. The effects
      of intragrating phase shift are also shown and discussed.

PMID- 12216880
TI  - Modification of the formulas for third-order aberration coefficients.
AB  - New parameters for calculation of third-order aberration coefficients (Seidel
      aberration coefficients) are introduced. The formulas for Seidel aberration
      coefficients are linear in these new variables. With these new variables it is
      possible to calculate the shape and the refractive index of the glass of the
      individual lenses of the optical system, which was not possible before.

PMID- 12216881
TI  - Measurement and modeling of optical performance of wire grids and liquid-crystal
      displays utilizing grid polarizers.
AB  - We studied the optical performance of a reflective wire-grid polarizer designed
      for visible light. The polarizer reflects E polarization and transmits H
      polarization with low losses. The studies of transmission and reflectivity of
      nonpolarized and polarized light from single grids and stacked grids show that
      the optical performance of wire-grid polarizers can be adequately described by
      representing the polarizer as an effective uniaxial medium with anisotropic
      absorption. The description facilitates the incorporation of the polarizers in
      modeling procedures widely used in the design of liquid-crystal devices. We
      present the modeling and measurement results of twisted-nematic devices with wire
      grid polarizers serving simultaneously as reflective polarizers, alignment
      layers, and back electrodes. The application of wire-grid polarizers for
      reflective liquid-crystal devices provides brightness enhancement, high contrast
      ratio at wide viewing angles, and elimination of viewing parallax.

PMID- 12216882
TI  - Alternative equations of magnetophotoelasticity and approximate solution of the
      inverse problem.
AB  - In magnetophotoelasticity, photoelastic models are investigated in a magnetic
      field in order to initiate rotation of the plane of polarization that is due to
      the Faraday effect. The method has been used for the measurement of stress
      distributions that are in equilibrium on the wave normal and therefore cannot be
      measured with the traditional photoelastic technique. In this category belong
      bending stresses in plates and shells and residual stresses in glass plates. Two
      new systems of equations of magnetophotoelasticity are derived. One of them
      describes evolution of the polarization of light in a magnetophotoelastic medium
      in terms of eigenvectors, the other in terms of distinctive parameters. For the
      latter system, an approximate closed-form solution has been found. The integral
      Wertheim law has been generalized for the case of stress states in equilibrium
      when rotation of the plane of polarization is present.

PMID- 12216883
TI  - Energy exchange between the Cartesian components of a paraxial beam in a uniaxial
      crystal.
AB  - The evolution of the optical power associated with the Cartesian components of a
      paraxial beam propagating along the optical axis in a uniaxial crystal is
      investigated. The energy exchange is found to undergo a saturation that is due to
      both diffraction and coupling between the chi- and gamma-field components; for
      linearly polarized circularly symmetric input beams, the asymptotic power
      exchange always amounts to a quarter of the total power. The general results are
      applied to the case of astigmatic Gaussian beams, which admits of a fully
      analytical description. The case of finite length crystals is also considered.

PMID- 12216884
TI  - Reduced-order model technique for the analysis of anisotropic inhomogeneous
      media: application to liquid-crystal displays.
AB  - Electromagnetic wave propagation in anisotropic inhomogeneous media is computed
      by a novel reduced-order model technique, which is based on the restriction of
      the Marcuvitz-Schwinger equations on Krylov subspaces and on the application of
      the singular-value decomposition. The model is derived from the standard coupled
      wave method and includes both wide-angle diffraction and light scattering at
      dielectric interfaces. The method, currently implemented for two-dimensional
      problems, was applied to the analysis of different liquid-crystal test cells.
      Numerical results are compared with those obtained through the application of the
      coupled-wave method and the Jones method and with experimental microscopic
      measurements.

PMID- 12216885
TI  - Optical scanning holography as a technique for high-resolution three-dimensional
      biological microscopy.
AB  - The applicability of optical scanning holography (OSH) to the field of
      microscopic imaging for biological applications is assessed. A generalized
      mathematical description of OSH that takes into account polarization effects,
      high numerical apertures, and generalized illumination wave fronts is presented.
      This description is used to show that the proposed single-beam scanning technique
      relaxes the restrictions under which OSH functions correctly compared with the
      conventional double-beam scanning method. It is also shown that, although in
      general OSH is restricted to thin samples, this condition can be relaxed in
      nonrefracting fluorescence samples, which are of importance in biological
      microscopy.

PMID- 12216886
TI  - Analysis of enhanced second-harmonic generation in periodic nanostructures using
      modified rigorous coupled-wave analysis in the undepleted-pump approximation.
AB  - We present an extension of the rigorous coupled-wave analysis technique to
      analyze second-harmonic generation (SHG) in periodic optical nanostructures in
      the undepleted-pump approximation. We apply this method to analyze SHG in two
      example nanostructures for which we predict enhanced nonlinearity due to
      transverse near-field localization of the fundamental optical field in the
      nonlinear material. First, we examine a periodic nanostructure that yields up to
      twice the transmitted SHG intensity output compared with the bulk nonlinear
      material but only for small nanostructure depths because of mismatch of the
      fundamental and second-harmonic mode phase velocities. Second, we develop and
      analyze a modified nanostructure and find that this nanostructure concurrently
      achieves transverse localization and phase matching for SHG. In principle, this
      permits an arbitrary coherent interaction length, and for several specific
      nanostructure depths we predict a transmitted SHG intensity output more than two
      orders of magnitude greater than that of the bulk material.

PMID- 12216887
TI  - HOD selects Walther to be president-elect.

PMID- 12216888
TI  - Nashville convention delivers a grand time.

PMID- 12216889
TI  - President Howell sees veterinary profession in transition.

PMID- 12216890
TI  - Delegates approve 15 amendments.

PMID- 12216891
TI  - Veterinarians have role in war on terror, says congressman.

PMID- 12216892
TI  - Disagrees with AVMA's position on induced molting.

PMID- 12216893
TI  - Reported ELISA results thought to be inaccurate.

PMID- 12216894
TI  - Remembering Dr. Bustad.

PMID- 12216895
TI  - Responses to Dr. Brandt's letter to AVMA members.

PMID- 12216896
TI  - Responses to Dr. Brandt's letter to AVMA members.

PMID- 12216897
TI  - Responses to Dr. Brandt's letter to AVMA members.

PMID- 12216898
TI  - What is your diagnosis? An osseous mass associated with the lateral aspect of the
      tuber calcaneus, with some degree of soft-tissue swelling.

PMID- 12216899
TI  - Use of atopic dogs to investigate adverse reactions to food.

PMID- 12216900
TI  - Dead animals, abandoned animals, and animals held for payment of fee--a
      veterinarian's options.

PMID- 12216901
TI  - Evaluation of an oscillometric blood pressure monitor for use in anesthetized
      cats.
AB  - OBJECTIVE: To determine accuracy of an oscillometric blood pressure monitor used
      over a wide range of pressures in anesthetized cats. DESIGN: Prospective study.
      ANIMALS: 6 healthy cats. PROCEDURE: 4 female cats and 2 male cats that weighed
      2.7 to 4.5 kg (5.9 to 9.9 lb) and were 2 to 8 years old were anesthetized. Blood
      pressure was measured directly with an arterial catheter placed in the right
      femoral artery and indirectly from the left antebrachium by use of an
      oscillometric monitor. A series of diastolic arterial pressure (DAP), mean
      arterial pressure (MAP), and systolic arterial pressure (SAP) measurements were
      obtained during hypotension, normotension, and hypertension. Values obtained
      indirectly and directly were compared. RESULTS: The oscillometric monitor was
      accurate for DAP and MAP throughout the entire pressure range and met the
      standards of the Association for the Advancement of Medical Instrumentation (mean
      +/- SD difference from values obtained directly, < or = 5 +/- 8 mm Hg). The SAP
      was increasingly underestimated with increasing overall pressure; mean
      differences from direct measurements were -5.2, -12.1, and -17.7 mm Hg during
      hypo-, normo-, and hypertension, respectively. Standard deviations for SAP were
      all < or = 8 mm Hg. The monitor gave readings during all attempts. The direct
      blood pressure recording system appeared to perform well with neither under- nor
      overdamping. CONCLUSIONS AND CLINICAL RELEVANCE: Except for a minor
      underestimation of SAP during normo- and hypertension, the oscillometric monitor
      yielded reliable and easily obtainable blood pressure measurements in
      anesthetized cats.

PMID- 12216902
TI  - Use of carbon dioxide laser for onychectomy in cats.
AB  - OBJECTIVE: To compare postoperative signs of discomfort and complications
      associated with use of CO2 laser for onychectomy with those of the scalpel
      technique in cats. DESIGN: Prospective, randomized, masked clinical trial.
      ANIMALS: 20 client-owned cats. PROCEDURE: Forelimb feet (right, left) were
      randomly assigned to laser and scalpel treatment groups. Signs of discomfort
      (lameness and signs of pain) and complications (hemorrhage, swelling, and
      discharge) were assessed on days 0, 1, and 7. Surgeries were performed by 1
      experienced surgeon. Evaluations were performed by 2 individuals without
      knowledge of treatment group. Signs of discomfort and complications were scored
      on scales of 0 to 8 and 0 to 9, respectively. RESULTS: Onychectomy did not result
      in high discomfort or complication scores 1 day after surgery, regardless of
      technique used, although the laser-treated group had significantly lower scores
      for signs of discomfort and complications. Seven days after surgery, significant
      differences were not detected between groups for signs of discomfort or
      complications. CONCLUSIONS AND CLINICAL RELEVANCE: The CO2 laser can be an
      excellent tool for onychectomy in cats, with excellent hemostasis and minimal
      postoperative discomfort and complications. Differences in discomfort and
      complications between groups treated via scalpel versus CO2 laser were not
      clinically relevant and were only observed 1 day after surgery.

PMID- 12216903
TI  - Effects of long-term administration of enalapril on clinical indicators of renal
      function in dogs with compensated mitral regurgitation.
AB  - OBJECTIVE: To determine the effect of long-term administration of enalapril on
      renal function in dogs with severe, compensated mitral regurgitation. DESIGN:
      Randomized controlled trial. ANIMALS: 139 dogs with mitral regurgitation but
      without overt signs of heart failure. PROCEDURE: Dogs were randomly assigned to
      be treated with enalapril (0.5 mg/kg [0.23 mg/lb], PO, q 24 h) or placebo, and
      serum creatinine and urea nitrogen concentrations were measured at regular
      intervals for up to 26 months. RESULTS: Adequate information on renal function
      was obtained from 132 dogs; follow-up time ranged from 0.5 to 26 months (median,
      12 months). Mean serum creatinine and urea nitrogen concentrations were not
      significantly different between dogs receiving enalapril and dogs receiving the
      placebo at any time, nor were concentrations significantly different from
      baseline concentrations. Proportions of dogs that developed azotemia or that had
      a +/- 35% increase in serum creatinine or urea nitrogen concentration were also
      not significantly different between groups. CONCLUSIONS: And Clinical Relevance:
      Results suggest that administration of enalapril for up to 2 years did not have
      any demonstrable adverse effects on renal function in dogs with severe,
      compensated mitral regurgitation.

PMID- 12216904
TI  - Surgical treatment of an intramedullary spinal cord hamartoma in a dog.
AB  - A 9-year-old spayed female Golden Retriever was examined because of progressive
      hind limb lameness. Magnetic resonance imaging of the thoracic and lumbar
      portions of the vertebral column revealed a focal, contrast-enhancing,
      intramedullary spinal cord mass. The history, signalment, and magnetic resonance
      findings were suggestive of spinal cord neoplasia. A hemilaminectomy, durotomy,
      and longitudinal myelotomy were performed, and a 1 X 1-cm mass that contained
      numerous blood vessels was removed with blunt dissection. Results of histologic
      examination and immunohistochemical staining of the mass suggested that it was a
      hamartoma. The dog improved after surgery, with no evidence of a recurrence of
      clinical signs 14 months after surgery. Vascular malformations of the CNS in dogs
      include hamartomas, hemangiomas, angiomas, hemangioblastomas, meningocerebral
      hemangiomatosis, and arteriovenous malformations. A hamartoma is a non-neoplastic
      overgrowth of cells or an improper proportion of cells that are normally in the
      involved tissue. Although magnetic resonance imaging may be helpful in
      determining the extent of the lesion in dogs with vascular malforrmations, it
      cannot be used to distinguish neoplastic from non-neoplastic formations. Excision
      may result in a good outcome for dogs with an intramedullary spinal cord
      hamartoma.

PMID- 12216905
TI  - Open versus closed bilateral anal sacculectomy for treatment of non-neoplastic
      anal sac disease in dogs: 95 cases (1969-1994).
AB  - OBJECTIVE: To determine complications associated with anal sacculectomy in dogs
      with non-neoplastic anal sac disease and compare complication rates for open
      versus closed techniques. DESIGN: Retrospective study. ANIMALS: 95 dogs.
      PROCEDURE: Medical records were reviewed for information on signalment, history,
      physical examination findings, type of anal sac disease, surgical technique
      (closed, standard open [surgery performed prior to 19801, or modified open
      [surgery performed after 19801), and postoperative complications. RESULTS: In 57
      dogs, a closed technique was used, and in 38, an open technique was used. Only 3
      dogs developed short-term complications (excessive drainage, scooting and
      inflammation, and seroma formation), and 14 developed long-term complications
      (continued licking of the surgery site, fecal incontinence, fistulation, and
      stricture formation). Development of postoperative complications was
      significantly associated with surgical technique. Dogs that underwent standard
      open sacculectomy prior to 1980 were 13.67 times as likely to have a long-term
      complication as were dogs that underwent closed sacculectomy. Weight of the dog,
      type of anal sac disease, age at the time of surgery, and whether the wound was
      closed surgically were not significantly associated with whether dogs developed
      postoperative complications. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest
      that anal sacculectomy is a safe and effective treatment for non-neoplastic anal
      sac disease in dogs and is associated with a low rate of complications. The
      standard open technique was associated with the greatest number of complications,
      whereas complication rates for the closed and modified open techniques were
      similar to each other.

PMID- 12216906
TI  - Results of preemptive epidural administration of morphine with or without
      bupivacaine in dogs and cats undergoing surgery: 265 cases (1997-1999).
AB  - OBJECTIVE: To determine prevalence of adverse effects associated with epidural
      administration of morphine with or without bupivacaine in dogs and cats
      undergoing surgery and evaluate effects of epidural administration of morphine on
      postoperative pain severity. DESIGN: Retrospective study. ANIMALS: 242 dogs and
      23 cats. PROCEDURE: Morphine with or without bupivacaine was administered prior
      to surgery with a Tuohy needle, spinal needle, or epidural catheter. In 18 dogs
      that underwent surgery twice, results of preemptive epidural administration of
      morphine with or without bupivacaine were compared with results of systemic
      administration of oxymorphone and ketoprofen. RESULTS: The delivered fraction of
      isoflurane was significantly lower in animals given morphine and bupivacaine than
      in animals given morphine alone. Analgesia was of significantly longer duration
      in dogs given morphine and bupivacaine than in dogs given morphine alone. During
      anesthesia, mild respiratory and cardiovascular depression was reported. Seven
      dogs and 2 cats had urine retention, and 2 dogs developed pruritus. Six dogs
      vomited when a second dose of morphine was given epidurally the day after
      surgery. Eight of 72 dogs had delayed hair growth. In 18 dogs that underwent
      surgery twice, the delivered fraction of isoflurane was significantly lower and
      the duration of analgesia was significantly longer when morphine with or without
      bupivacaine was given epidurally than when oxymorphone and ketoprofen were given.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that preemptive epidural
      administration of morphine with or without bupivacaine is a safe and effective
      method of inducing long-lasting analgesia in dogs and cats and is superior to
      standard management of postoperative pain with repeated injection of oxymorphone
      and ketoprofen.

PMID- 12216907
TI  - Potentially hazardous sulfur conditions on beef cattle ranches in the United
      States.
AB  - OBJECTIVE: To analyze the sulfur content of water and forage samples from a
      geographically diverse sample of beef cow-calf operations in the United States
      and to estimate frequency and distribution of premises where forage and water
      resources could result in consumption of hazardous amounts of sulfur by cattle.
      DESIGN: Cross-sectional study. SAMPLE POPULATION: 709 forage samples from 678
      beef cow-calf operations and individual water samples from 498 operations in 23
      states. PROCEDURE: Sulfur content of forage samples and sulfate concentration of
      water samples were measured. Total sulfur intake was estimated for pairs of
      forage and water samples. RESULTS: Total sulfur intake was estimated for 454
      pairs of forage and water samples. In general, highest forage sulfur contents did
      not coincide with highest water sulfate concentrations. Overall, 52 of the 454
      (11.5%) sample pairs were estimated to yield total sulfur intake (as a percentage
      of dry matter) > or = 0.4%, assuming water intake during conditions of high
      ambient temperature. Most of these premises were in north-central (n = 19) or
      western (19) states. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that on
      numerous beef cow-calf operations throughout the United States, consumption of
      forage and water could result in excessively high sulfur intake. All water
      sources and dietary components should be evaluated when assessing total sulfur
      intake. Knowledge of total sulfur intake may be useful in reducing the risk of
      sulfur-associated health and performance problems in beef cattle.

PMID- 12216908
TI  - Predicted ages of dairy calves when colostrum-derived bovine viral diarrhea virus
      antibodies would no longer offer protection against disease or interfere with
      vaccination.
AB  - OBJECTIVE: To develop models that could be used to predict, for dairy calves, the
      age at which colostrum-derived bovine viral diarrhea virus (BVDV) antibodies
      would no longer offer protection against infection or interfere with vaccination.
      DESIGN: Prospective observational field study. ANIMALS: 466 calves in 2
      California dairy herds. PROCEDURE: Serum BVDV neutralizing antibody titers were
      measured from birth through 300 days of age. The age by which colostrum-derived
      BVDV antibodies had decayed sufficiently that calves were considered susceptible
      to BVDV infection (ie, titer < or = 1:16) or calves became seronegative was
      modeled with survival analysis methods. Mixed-effects regression analysis was
      used to model colostrum-derived BVDV antibody titer for any given age. RESULTS:
      Half the calves in both herds became seronegative for BVDV type I by 141 days of
      age and for BVDV type II by 114 days of age. Rate of antibody decay was
      significantly associated with antibody titer at 1 to 3 days of age and with
      whether calves were congenitally infected with BVDV. Three-month-old calves were
      predicted to have a mean BVDV type-I antibody titer of 1:32 and a mean BVDV type
      II antibody titer of 1:16. CONCLUSIONS AND CLINICAL RELEVANCE: Results provide an
      improved understanding of the decay of BVDV-specific colostrum-derived antibodies
      in dairy calves raised under typical field conditions. Knowledge of the age when
      the calf herd becomes susceptible can be useful when designing vaccination
      programs aimed at minimizing negative effects of colostrum-derived antibodies on
      vaccine efficacy while maximizing overall calf herd immunity.

PMID- 12216910
TI  - Use of pneumocystoplasty for overinflation of the swim bladder in a goldfish.
AB  - A Ryukin goldfish was evaluated because of a 6-month history of progressive
      abdominal distention and positive buoyancy. Overinflation of the swim bladder was
      diagnosed, and the fish was anesthetized with tricaine methanesulfonate.
      Archimedes' principle was used to determine the volume of swim bladder that was
      removed surgically. The caudal swim bladder was exteriorized through an abdominal
      incision and 2 surgical clips were placed across it to limit its size. After
      surgery, the fish remained in a state of negative buoyancy in sternal and lateral
      recumbency on the bottom of the tank. Sutures were removed 15 days after surgery,
      but the fish died 24 days after surgery. A full necropsy could not be performed
      because of autolysis of the tissues, but the surgical clips and the swim bladder
      appeared unremarkable. Pneumocystoplasty may be a viable treatment for this
      condition.

PMID- 12216909
TI  - Hemorrhagic bowel syndrome in dairy cattle: 22 cases (1997-2000).
AB  - OBJECTIVE: To determine signalment, history, and clinical, necropsy, and
      microbiologic findings in dairy cows with hemorrhagic bowel syndrome. DESIGN:
      Retrospective study. ANIMALS: 22 adult dairy cows from a single farm in Colorado.
      PROCEDURE: Medical records were reviewed for information on signalment, medical
      and reproductive history, the owner's chief complaints, results of physical
      examinations and ancillary diagnostic tests, treatment and response to treatment,
      results of microbiologic testing, and, if applicable, postmortem findings.
      RESULTS: Common clinical signs were acute signs of profound depression, decreased
      milk production, tachycardia, ruminal stasis, abdominal distention, and dark
      clotted blood in the feces. Rectal examination revealed distended loops of small
      intestine in 7 of 14 cows. Transabdominal ultrasonography revealed small
      intestinal ileus and distention in 12 of 12 cows and homogeneous echogenic
      intraluminal material compatible with intraluminal hemorrhage and clot formation
      in 4. Seven of 8 cows treated medically died; 9 of 13 cows that underwent surgery
      died or were euthanatized. Clostridium perfringens was isolated from fecal
      samples from 17 of 20 cows. The most common morphologic diagnosis at necropsy was
      severe necrohemorrhagic enteritis or jejunitis with intraluminal hemorrhage or
      blood clots. The most prominent histologic finding was severe, segmental
      submucosal hemorrhage and edema of the small intestine. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results confirm that in adult cattle, hemorrhagic bowel syndrome is a
      sporadic acute intestinal disorder characterized by intraluminal hemorrhage and
      obstruction of the small intestine. Clostridium perfringens was consistently
      isolated from the feces of affected cows. The prognosis for affected cows was
      grave.

PMID- 12216911
TI  - Wanted: an improved public message.

PMID- 12216912
TI  - Dentists turn treatment into entertainment.

PMID- 12216913
TI  - Treatment planning in the 21st century: what's new?
AB  - Many variables affect treatment planning, and it is important for clinicians to
      consider why they plan certain procedures for patient care. New materials,
      technologies, and products are constantly being introduced and affect decision
      making in dentistry. In addition, patients are more informed, have higher
      esthetic concerns, and want a greater stake in treatment planning decisions than
      ever before. How dentists treatment plan needs to reflect the many influences on
      final treatment outcome. The purpose of this paper is to outline how treatment
      planning has changed in dentistry with the goal of providing the general dentist
      updated information to develop a cohesive treatment plan.

PMID- 12216914
TI  - Better understanding your patient from a psychological perspective: early
      identification of problem behaviors affecting the dental office.
AB  - Early assessment of problem patient behaviors can be a complex and time-consuming
      task. These negative behaviors can frequently interrupt and misdirect treatment
      goals. Most dentists, due to private practice demands, do not have the time and
      training to assess these behaviors. The emotional stability of each patient is
      taken for granted. Subtle negative behavioral clues can be detected during
      medical history taking and the initial patient interview. Current prescription
      medications can also provide clues concerning past or current treatment for
      depression, anxiety, psychiatric problems, or substance abuse. The burden of
      properly assessing behaviors and their impact on dental treatment rests on the
      dentist's acumen in history taking. All practices have some difficult patients.
      It is important that dentists recognize patients who have special needs such as
      those with high anxiety, dependency, depression, obsessional somatic focus, or
      prior negative dental experiences.

PMID- 12216915
TI  - Thick vs. thin gingival tissue: a key determinant in tissue response to disease
      and restorative treatment.
AB  - During the treatment planning process, it is important for clinicians to
      appreciate that the differences in gingival tissue can affect treatment outcomes.
      The concept of thick vs. thin gingiva has previously been introduced. This
      concept has been expanded to describe the different ways these tissue types
      respond to inflammation, restorative trauma, and parafunctional habits. The
      resulting defects from these traumatic events will dictate varying treatment
      management modalities. As restorative dentists begin to appreciate the
      differences in gingival morphology, they will discover that working with thick
      gingiva is easier and more predictable. In the past, restorative dentists had no
      options for influencing the tissue quality they had to work with during
      restorative procedures. Recent advances in periodontal surgery have made it
      possible not only to reposition tissues to meet esthetic demands, but also to
      change the tissue quality of the restorative environment for more-predictable
      treatment outcomes.

PMID- 12216916
TI  - Considerations for anterior implant esthetics.
AB  - There are several factors to consider when restoring failing dentition in the
      anterior region. While a tooth can be replaced with an implant, achieving an
      esthetic result is challenging. The dental team must evaluate numerous criteria
      to define the optimal treatment plan. Among the considerations are whether to
      extract the tooth and perform immediate implant replacement or to perform a ridge
      preservation procedure. This article presents diagnostic determinants to help
      decide the most appropriate course of therapy to achieve functional and esthetic
      results.

PMID- 12216917
TI  - Prerestorative considerations for cosmetic dentistry.
AB  - Helping patients improve their appearance with esthetic procedures can be very
      rewarding. Optimal esthetic results often require a multidisciplinary approach
      and sequenced care. Treatment planning with a team approach offers the potential
      for multiple perspectives and the best opportunity to achieve the optimal
      results.

PMID- 12216918
TI  - Bench-pressing 500 mg.

PMID- 12216919
TI  - Primary pulmonary hypertension--an update.

PMID- 12216920
TI  - Renal artery stenosis: diagnosis and management.

PMID- 12216921
TI  - Racial variation in risk factors and occurrence of acute myocardial infarction:
      comparison between Arab and South Asian men in Kuwait.
AB  - BACKGROUND: There are little data available on the rates of occurrence, risk
      factors and mortality due to acute myocardial infarction among the various ethnic
      groups living in Middle-East countries. Therefore, we did a study to compare
      Arabs and South Asians living in Kuwait. METHODS AND RESULTS: The data for this
      retrospective study were collected from the computerized database of the Coronary
      Care Unit at the Mubarak Al-Kabeer Hospital (a 476-bed teaching hospital) and the
      1997-2000 Census data for the State of Kuwait. Arab and South Asian men above 25
      years admitted between September 1997 and August 2000 with a diagnosis of acute
      myocardial infarction were included in the study A total of 866 Arabs and 277
      South Asian men were admitted. The rate of admission for the entire patient
      population was two-fold higher among Arabs as compared with South Asians
      (6.7/1000 population and 3.3/1,000, respectively). Diabetes mellitus was present
      in 453 Arabs (52.3%) and 109 South Asians (39.4%) (p< or = 0.001) of those >25
      years of age. Hypertension was recorded in 247 Arabs (28.5%) and 57 South Asians
      (20.6%) (p < or = 0.01). Among patients <55 years of age (454 Arabs and 226 South
      Asians); the rate of admission was 4.0/1,000 in Arabs and 3.5/1,000 in South
      Asians (not significant). Hypertension was present in 97 Arabs (21.3%) and 43
      South Asians (19%) (not significant). Diabetes mellitus was present in 202 Arabs
      (44.5%) and 80 South Asians (35.4%) (p < or = 0.05). Smoking was recorded in 353
      Arabs (77.8%) and 160 South Asians (70.8%) (notsignificant). Hypercholesterolemia
      was presentin 182 (40.1%) and 88 (39%), respectively (not significant). While in
      hospital, 11 Arabs and 9 South Asians died (not significant). CONCLUSIONS: Among
      men >55 and <75 years of age, Arabs had a higher rate of admission with acute
      myocardial infarction compared with men of South Asian origin. The incidence of
      diabetes and hypertension was significantly higher among Arabs in this age group.
      In younger patients (<55 years), the rate of acute myocardial infarction was not
      different between the two groups; however, diabetes was present more often among
      Arabs. The smoking rate is very high in both groups and is an important risk
      factor for both Arab and South Asian men living in the Middle East.

PMID- 12216922
TI  - Congenital coronary anomalies of origin and distribution in adults: a coronary
      arteriographic study.
AB  - BACKGROUND: Coronary anomalies should be recognized to avoid problems during
      coronary intervention and cardiac surgery. METHODS AND RESULTS: We
      retrospectively reviewed 7400 coronary angiograms to find out the pattern and
      incidence of coronary anomalies of origin and distribution. We excluded patients
      with congenital heart diseases, coronary artery fistulae and patients with
      separate origin of the conus artery. and found 34 cases (0.46%) (22 males), mean
      age 50.7 +/- 12 years with coronary anomalies. Six cases underwent angiography
      prior to valve replacement and the rest were part of the evaluation for
      atherosclerotic coronary artery disease. The most common anomaly was separate
      origins of the left anterior descending coronary artery and left circumflex
      coronary artery [n=12 (35.3%)]. The next most common anomalies were origins of
      the right coronary artery from the left coronary sinus [n=7 (20.6%)] and left
      circumflex artery from the right sinus [n=6 (20%)]. A single coronary artery was
      seen in 3 cases (8.8%) which included one case of postmyocardial infarction
      ventricular septal rupture with triple-vessel disease, and another with two small
      coronary fistulae. One case each of the following coronary anomalies was found:
      (i) double right coronary artery, (ii) left anterior descending coronary artery
      from the right coronary sinus, (iii) all three coronary arteries originating
      separately from the right sinus, and (iv) left main coronary artery from the
      right sinus. Of these 34 patients, 11 (32.4%) had significant atherosclerotic
      disease in the anomalous vessel. CONCLUSIONS: The incidence of primary coronary
      anomaly seems to be less than that in earlier reports, but the pattern of
      anomalies appears to be similar.

PMID- 12216923
TI  - Pulmonary autograft mitral valve replacement: initial experience with the Ross II
      procedure.
AB  - BACKGROUND: The renewed interest in mitral valve replacement with a pulmonary
      autograft encouraged us to perform this procedure in selected patients. METHODS
      AND RESULTS: From August 2000 to February 2002, 10 patients between 30 and 52
      years of age with calcific mitral valvular disease underwent the Ross II
      procedure. Patients were either in New York Heart Association functional class
      III (7/10) or IV (3/10). Transthoracic echocardiography was done in all the
      patients to confirm the diagnosis. A pulmonary autograft was used to replace the
      diseased mitral valve. Intraoperative transesophageal echocardiography confirmed
      normal functioning of the autograft. There were 2 early deaths. The 8 survivors
      are in New York Heart Association functional class I with excellent autograft and
      homograft function at a follow-up of 2-20 months (mean 9 months). CONCLUSIONS:
      This procedure is a viable option for mitral valve replacement in patients with
      calcific mitral valve disease. However, the procedure is technically demanding
      and requires a valve bank.

PMID- 12216924
TI  - Minimally invasive mitral valve surgery.
AB  - BACKGROUND: To reduce surgical trauma and the drawbacks associated with
      sternotomy, we performed robotically controlled, video-assisted mitral valve
      surgery, using either the port-access or the transthoracic clamp technique.
      METHODS AND RESULTS: Between September 1997 and September 2000, 221 patients (78
      males, 143 females) underwent mitral valve surgery through a small right
      minithoracotomy using the port-access endovascular cardiopulmonary bypass system.
      Mitral valve exposure was facilitated with an endoscope attached to a voice
      controlled robotic arm (AESOP 3000) allowing stabilization and voice-activated
      camera positioning. Twenty-six patients underwent mitral valve repair and 195 had
      valve replacement. In 197 patients, mitral valve surgery was the primary
      operation, while 24 were redo cases. Skin-to-skin mean operating time was 3.5 +/-
      1.2 hours and aortic cross-clamp time was 58 +/- 16 min, mean intensive care unit
      stay was 22 +/- 7 hours and hospital stay 6.4 +/- 1.2 days. There was no re
      exploration for bleeding. There was no late death or re-operation on mean follow
      up of 16.4 +/- 12.2 months. Patients showed improvement in their NYHA functional
      class from 2.6 +/- 0.5 to 1.4 +/- 0.8 postoperatively. Outcomes were compared
      with those of our previous 220 patients who underwent mitral valve surgery with
      the median sternotomy approach. CONCLUSIONS: The use of video and robotic
      assistance in port-access mitral valve surgery not only minimizes the length of
      the incision, but also gives full visualization of the entire mitral valve
      apparatus. This approach provides comparable results with the sternotomy
      approach, as well as marked advantages of reduced intensive care unit stay. ,ower
      blood transfusion requirement, better cosmesis and earlier hospital discharge.

PMID- 12216925
TI  - Relation of C-reactive protein levels to presence, extent, and severity of
      angiographic coronary artery disease.
AB  - BACKGROUND: C-reactive protein is a valid marker of cardiovascular risk. It is
      not known whether C-reactive protein is a marker of atherosclerotic burden or
      whether it reflects a process (e.g. inflammatory fibrous cap degradation) leading
      to acute coronary events. This study was performed to determine whetherthe
      concentration of C-reactive protein is associated with coronary atherosclerosis
      assessed by coronary angiography. METHODS AND RESULTS: We studied a total of 100
      men and women (41 women, 59 men, mean age 63.7 +/- 11.0 years) who were referred
      for coronary angiography. Baseline data collection comprised clinical
      characteristics and conventional risk factors for coronary artery disease, levels
      of serum lipids and fasting total homocysteine levels. The relation between serum
      C-reactive protein levels and the severity and extension of coronary lesions was
      studied. The coronary angiograms were evaluated in a blinded manner according to
      three scores: vessel score (0-3 points for 0-3 vessels with coronary artery
      disease), stenosis score (0-3 points: number and severity of coronary stenoses or
      lesions; 0 for no, 1 for coronary lesion with diameter stenosis less than 50%, 2
      for 50%-75%, and 3 for more than 75% diameter stenosis), and extent score (0-3
      points; segment-extension of all coronary lesions within the total coronary
      vessel length). According to the total score values obtained, groups for coronary
      artery disease risk were defined and analyzed forcorrelations with age and levels
      of total cholesterol. high-density lipoprotein cholesterol, low-density
      lipoprotein cholesterol, triglycerides, fasting total homocysteine. and C
      reactive protein in serum. From the 100 patients, 40 were found to have no or
      minimal coronary artery disease (group A; score 0-3), 33 had moderate (group B;
      score 4-8) and 27 had severe (group C: score more than 8) coronary artery disease
      assessed by coronary angiography. Estimates of the relative risk of coronary
      heart disease for the third quintile of serum C-reactive protein as compared with
      the first quintile were 1.79 (95 percent confidence interval 1.23-2.39). Serum C
      reactive protein levels were 3.54 (+/- 7.07) mg/L, 11.41 (+/- 13.5) mg/L and 5.66
      (+/- 8.32) mg/L in groups A, B and C and represented an independent risk factor
      for the presence of coronary artery disease assessed by coronary angiography
      (p<0.01). With step-wise logistic regression analyses, use of C-reactive protein
      values maintained the ability to predict the probability of coronary artery
      disease. Moreover, the presence of angiographic coronary artery disease was
      associated with patient age (p=0.048), male sex (p<0.01), high LDL-cholesterol
      levels (p=0.02), low HDL-cholesterol levels (p=0.02), high plasma fibrinogen
      levels (p<0.01) and high fasting total homocysteine levels (p=0.04). CONCLUSIONS:
      These results suggest that the serum concentration of C-reactive protein is
      associated with presence, but not severity, of coronary artery disease in
      patients referred for coronary angiography.

PMID- 12216926
TI  - Autologous right atrial patch for closure of atrial septal defect.
AB  - BACKGROUND: Prosthetic or pericardial patches used for the closure of atrial
      septal defects are associated with infrequent but definite problems. As an
      alternative, we used a right atrial free-wall patch in 12 patients, 7-54 years of
      age. METHODS AND RESULTS: The presence of a large secundum atrial septal defect
      (n=2). associated mitral valve regurgitation (n=7), primum atrial septal defect
      (n=2) and sinus venosus defect (n=1) necessitated the use of a patch. The mitral
      valve was repaired in 9 patients (including 2 with a primum defect). One patient
      with a primum defect who was in congestive heart failure preoperatively died
      after 3 weeks due to refractory ventricular fibrillation. The remaining patients
      were discharged 5 to 7 days post procedure. No flow was detected across the
      septal patch on predischarge echocardiography. One patient underwent reoperation
      for failed mitral valve repair one month postprocedure. At reoperation, the patch
      was found to be intact with normal texture and without any suture dehiscence.
      Histopathological examination of the explanted patch revealed viable endothellum
      and subendothelial muscle on both surfaces of the patch. Follow-up ranged from 6
      to 36 months. Echocardiography performed after 6 to 32 months post procedure
      showed an intact patch with no residual defect. All the patients are in sinus
      rhythm. Holter monitoring performed in 6 patients was normal in all of them.
      Electrophysiological study was performed in 2 patients using a mapping catheter 4
      and 6 months post-procedure, respectively, and recorded normal atrial potentials
      from the site of the patch. CONCLUSIONS: The use of an autologous free right
      atrial wall as a patch for atrial septal defect closure is a viable option.

PMID- 12216927
TI  - Unusual ST-t changes in Ebstein's anomaly with occlusion of a nondominant
      coronary artery.
AB  - We present a case report of a patient of Ebstein's anomaly presenting with
      unusual ECG changes during acute coronary syndrome. The patient had undergone
      radiofrequency ablation of right posteroseptal accessory pathway. Two years
      later, he presented with acute chest pain. His ECG revealed ST elevation of 6-7
      mm in leads III, aVF. V3R and V1-V4 with atrioventricular dissociation. He was
      thrombolysed for the same. He subsequently underwent an angiogram for continuing
      angina. His angiogram showed a nondominant right coronary artery with a 95%
      stenosis. The left circumflex artery was dominant but without any stenosis. The
      left anterior descending artery was also normal. Angiogplasty and stenting were
      done for the right coronary artery lesion and the patient did well on follow-up.
      The ST segment elevation in the anterior precordial leads resulting from
      occlusion of a nondominant right coronary artery is unusual. The possible reason
      for this is the isolated right ventricular infarction in the absence of any left
      ventricular infarction. Thus the electrical current of injury resulting from the
      right ventricular infarction was unopposed by any counterbalancing current of
      injury from the inferior surface of the left ventricle.

PMID- 12216928
TI  - Massive primary chylopericardium in an infant.
AB  - We report a case of massive spontaneous primary chylopericardium in a 2-month-old
      infant who was successfully treated with thoracic duct ligation and creation of a
      posterior pericardial window.

PMID- 12216929
TI  - Sildenafil in the management of primary pulmonary hypertension.
AB  - Primary pulmonary hypertension is a rare disorder of unknown etiology with a poor
      prognosis. There is no cure, and drug therapy is effective in only a few
      patients. Calcium-channel antagonists and anticoagulants are the mainstay of
      therapy. Prostacyclin therapy leads to significant clinical improvement but its
      use is restricted due to high cost and complex drug delivery systems. Sildenafil
      is a selective vasodilator and has been shown to be effective in decreasing
      pulmonary vascular resistance in animal models of pulmonary hypertension. We
      report the use of sildenafil in two patients of primary pulmonary hypertension
      who were refractory to conventional drug therapy.

PMID- 12216930
TI  - Aortoarteritis with systemic lupus erythematosus and secondary antiphospholipid
      antibody syndrome: a rare association.
AB  - A 41-year-old woman diagnosed with aortoarteritis since 1988 was admitted with
      unstable angina. She also had anemia, thrombocytopenia, aortic regurgitation and
      pulmonary artery hypertension. She gave a history of recurrent fetal loss and
      myocardial infarction, following which angioplasty to the left anterior
      descending artery had been done. After investigation, a diagnosis of
      aortoarteritis with systemic lupus erythematosus and associated antiphospholipid
      antibody syndrome was made. Aortoarteritis may coexist with systemic lupus
      erythematosus and associated antiphospholipid antibody syndrome.

PMID- 12216931
TI  - Left ventricle dynamics during pulsus alternans: insights from tissue velocity
      imaging.
AB  - A 34-year-old female patient with idiopathic dilated cardiomyopathy presented
      with hemodynamic pulsus alternans. Mitral annular tissue Doppler velocities
      showed reciprocal beat-to-beat alterations during systolic ejection and diastolic
      filling periods. Tissue velocity waves were unaltered during the isovolumic
      relaxation and contraction periods.

PMID- 12216932
TI  - Interventional therapy for multiple cardiac defects.
AB  - We describe a patient with a rare combination of coronary artery disease and
      congenital heart disease. The patient underwent successful complex and
      multivessel coronary angioplasty, balloon pulmonary valvuloplasty by the Inoue
      balloon and transcatheter closure of an atrial septal defect in a staged manner.
      It is technically feasible and safe to perform multiple interventions as an
      alternative to open heart surgery.

PMID- 12216933
TI  - Neurovascular rescue for embolic stroke following atrial septal defect closure.
AB  - Strokes following cardiac surgery occur in about 5% of patients. Intra-arterial
      thrombolysis is a good option in such a setting where intravenous thrombolysis is
      contraindicated, and when in-hospital strokes are detected well within the window
      for treatment and the chances of complete reperfusion are maximum. On
      postoperative day 4 after atrial septal defect correction, a 34-year-old woman
      with paroxysmal atrial fibrillation developed left middle cerebral artery stroke
      causing severe neurological deficits. Intra-arterial thrombolysis with urokinase
      led to remarkable recovery.

PMID- 12216934
TI  - Management of atrial fibrillation with reference to valvular heart disease.

PMID- 12216935
TI  - Isolated left ventricular noncompaction in an adult.

PMID- 12216936
TI  - Pollution, cytokines and atherosclerosis: an Indian perspective.

PMID- 12216938
TI  - Graded balloon atrial septostomy in severe pulmonary hypertension.

PMID- 12216937
TI  - 5-fluorouracil-associated cardiotoxicity.

PMID- 12216939
TI  - Pathways of allorecognition: implications for transplantation tolerance.
AB  - Allorecognition occurs when the host immune system detects same-species, non-self
      antigens and this is the trigger for allograft rejection. Host T cells detect
      these 'foreign' antigens which are mostly derived from a highly polymorphic
      region of the genome called the major histocompatibility complex. Allorecognition
      can occur by two distinct, but not mutually exclusive pathways: direct and
      indirect. The direct pathway results from the recognition of foreign major
      histocompatibility molecules, intact, on the surface of donor cells. Indirect
      allorecognition occurs when donor histocompatibility molecules are internalised,
      processed, and presented as peptides by host antigen presenting cells--this is
      the manner in which the immune system normally sees antigen. However, in addition
      to antigen recognition, T cell activation requires the provision of costimulatory
      signals, the prerogative of bone marrow-derived, specialised antigen-presenting
      cells (APC). Once these have been depleted from a transplanted organ, as occurs
      within weeks of transplantation, the parenchymal cells of the transplant are
      incapable of driving direct pathway activation of recipient T cells. Alloantigen
      recognition on these non-professional APCs may have a tolerising effect and
      indeed, the frequency of T cells reactive to the direct pathway diminishes with
      time irrespective of whether or not chronic transplant rejection occurs. This
      implies that while the direct pathway plays a dominant role in acute rejection,
      it is unlikely to contribute to chronic rejection. Assays of T cell responses
      have, however, found an association between the indirect pathway and chronic
      rejection and animal models support a role for the indirect pathway in both acute
      and chronic rejection. The indirect pathway is likely to be permanently active
      due to traffic of recipient APCs through the graft. The challenge that this poses
      in the pursuit of clinical tolerance is how to induce tolerance in T cells with
      indirect allospecificity. The answer may lie in manipulation of the environment
      of the interaction between the T cell and APC. Apart from recognition without
      costimulation, there are other circumstances when recognition without activation
      can occur although the in vivo relevance is uncertain. The presence of regulatory
      cytokines or inhibitory surface molecules either from a distinct regulatory cell,
      or as a negative feedback loop may prevent activation; this could also happen
      without sufficient stimulatory support: the final outcome is likely to be decided
      by the overall balance. Furthermore, some peptides may act as antagonists to T
      cell activation, usually when the agonist peptide is structurally very similar.
      It is hoped that the careful study of these mechanisms will reveal ways of
      ensuring allorecognition without activation and thus donor-specific tolerance.

PMID- 12216940
TI  - Levels of peripheral T cell tolerance.
AB  - The immune system is an adaptive defense system capable of specifically
      recognizing and eliminating an apparently limitless variety of foreign invaders.
      This highly specific response is provided by T and B lymphocytes. The enormous
      diversity of the antigen-specific receptors on these cells is generated by random
      rearrangement of the respective genes. The key challenge of such a defense system
      is to have as broad a T and B cell repertoire as possible in the absence of
      autoreactivity. This review summarizes mechanisms of peripheral T cell tolerance
      induction seen in various animal models. There is increasing evidence that
      tolerance to tissue-specific antigens can be induced by dendritic cells in the
      regional lymph nodes as well as by parenchymal cells like keratinocytes and
      hepatocytes in the respective tissues. Furthermore, tolerance induction should no
      longer only be viewed as prevention of T cell activation, as in certain systems
      activation of autoreactive T cells is insufficient to cause tissue damage. Thus,
      several tolerance mechanisms are operating in parallel under physiological
      conditions. With increasing knowledge of the molecular basis we will learn which
      mechanism is most suitable for therapeutic intervention.

PMID- 12216941
TI  - Minor H antigens: genes and peptides.
AB  - In this review, we describe the evidence from which the existence of non-MHC
      histocompatibility (H) antigens was deduced, the clinical setting of bone marrow
      transplantation in which they are important targets for T cell responses, and the
      current understanding of their molecular identity. We list the peptide epitopes,
      their MHC restriction molecules and the genes encoding them, of the human and
      murine minor H antigens now identified at the molecular level. Identification of
      the peptide epitopes allows T cell responses to these antigens following
      transplantation of MHC-matched, minor H-mismatched tissues to be enumerated using
      tetramers and elispot assays. This will facilitate analysis of correlations with
      HVG, GVH and GVL reactions in vivo. The potential to use minor H peptides to
      modulate in vivo responses to minor H antigens is discussed. Factors controlling
      immunodominance of T cell responses to one or a few of many potential minor H
      antigens remain to be elucidated but are important for making predictions of in
      vivo HVG, GVH and GVL responses and tailoring therapy after HLA-matched BMT and
      DLI.

PMID- 12216942
TI  - Rejection and recipient age.
AB  - In transplantation the risk of acute rejection decreases with recipient age. This
      is clearly illustrated in transplantation of a non-vascularised tissue, such as
      the cornea. In vascularised transplants, such as kidneys, acute rejection
      decreases with recipient age, but the phenomenon is obscured by the fact that
      chronic allograft nephropathy increases with age, and is further confounded by
      increased death from infectious disease and drug-related causes. The underlying
      cellular mechanisms responsible for this weakening of rejection are discussed, as
      is defective signal transduction leading to decreased activation of cells and
      decreased resistance to immunosuppressive drugs. This supports a view that less
      intensive immunosuppressive drug therapy is desirable in elderly recipients.
      Although pharmacokinetic studies are documented, there are no routine assays to
      measure efficacy of these drugs in individual patients. In summary, the decline
      in acute rejection with increasing recipient age may be due both to
      immunosenescence and decreased resistance to immunosuppressive drugs. Future
      assays to test these mechanisms could be used to tailor therapy to individual
      needs.

PMID- 12216943
TI  - Structural basis of immunogenicity.
AB  - The most important 'on-off' switch within the immune system are the T cells:
      these decide whether an immune response has to be induced and maintained or not.
      Since T cells glean their information from the interaction between their specific
      T cell receptor and a MHC-peptide complex, MHC molecules are invaluable
      information carriers. Each T cell is usually restricted to only one of the set of
      autologous MHC molecules, but it is nevertheless able to react upon contact with
      allogeneic MHC. For a given T cell, both the MHC molecule and presented peptide
      thus play a crucial role in antigen recognition. MHC molecules govern the allele
      specific restriction of T cells or, most important in transplantation immunology,
      allo-specific recognition, which is often peptide-independent. Peptides serving
      as MHC ligands are able either to tolerise T cells if presented under certain
      circumstances, or to activate T cells if presented by professional antigen
      presenting cells in an inflammatory environment. The vast polymorphism of human
      MHC molecules combined with the complexity of thousands of different peptides
      presented by each allelic product provide the utmost heterogeneity. During the
      past few years, a huge amount of information about MHC-bound peptides has been
      compiled that helps us to understand the structural basis of immunogenicity. This
      contribution describes the characteristics of antigen processing within the MHC
      class I pathway, from proteasomal processing to the rules of MHC binding. Our
      current knowledge enables the exact description of many processes within the
      class I processing pathway and paves the way for the prediction of potential T
      cell epitopes by employing the rules of peptide presentation.

PMID- 12216944
TI  - Predictive parameters for in vivo alloreactivity.
AB  - Despite optimal HLA matching and a negative serological crossmatch, confrontation
      with allogeneic cells by organ- or stem-cell transplantation or platelet
      transfusion, can lead to an alloimmune response resulting in graft rejection,
      graft vs. host disease or platelet refractoriness. It would be attractive to be
      able to select beforehand those donor/recipient combinations, that do not lead to
      a destructive alloimmune response and exclude transplantation or transfusion with
      donors, that induce a strong alloimmune reaction. Many predictive parameters have
      been identified on the basis of retrospective analysis of graft survival data,
      and the results of in vitro tests to measure T and B cell alloreactivity.
      However, most of these parameters have shown to be relevant when a statistical
      analysis is performed on the population level but do not have a direct impact for
      the individual patient. An exception is a molecularly based algorithm, called HLA
      matchmaker, which seems to predict which HLA mismatches do not lead to
      alloantibody formation in a particular individual. Prediction of T cell
      alloreactivity is more difficult and will need the development of additional in
      vitro tools or adaptation of the HLA matchmaker program. Although the direct
      clinical implication of NK cell mediated allorecognition is not clear yet, this
      may be a complicating factor when establishing solid parameters for the
      prediction of an alloimmune reaction in vivo.

PMID- 12216945
TI  - The extent and analysis of cytokine and cytokine receptor gene polymorphism.
AB  - Cytokines play an important role in the regulation of normal immune function. In
      recent years cytokines and their receptors have been shown to be highly
      polymorphic. Polymorphisms in these genes have been associated with a number of
      immune diseases as well as organ transplant complications. The current disease
      association data is confusing and often contradictory. Whilst single locus
      analyses are the predominant form of cytokine polymorphism analysis, the use of
      polymorphic haplotypes is becoming increasingly common. This may help to give a
      clearer picture of the association of cytokine polymorphism with immune
      disfunction.

PMID- 12216946
TI  - Natural killer cells and their receptors.
AB  - Natural killer (NK) cells have been known for a long time to be a very important
      component of the innate immune system. However, it is only during the last 10
      years that knowledge of their receptors has emerged. Described in the present
      review are those receptor families killer inhibitory receptor (KIR) (belonging to
      the immunoglobulin superfamily), and killer lectin like receptor (KLR) CD94/NKG2,
      that both use HLA as a ligand and have inhibiting and activating types of
      receptors, and natural cytotoxic receptors (NCR) which do not associate with HLA.
      Association of the receptor gives rise to either an inhibiting or activating
      signal leading to either failure or success in lysing a target cell. The KIR
      receptors are very polymorphic both in the number of genes expressed in an
      individual and the alleles present for a gene. They would appear to have had a
      rapid evolution compared to the CD94/NKG2 receptors. The roles that NK cells and
      their receptors have with various facets of transplantation, disease, pregnancy
      and control of virus infection in humans are described.

PMID- 12216947
TI  - Platelet antigens. The role of human platelet alloantigens (HPA) in blood
      transfusion and transplantation.
AB  - In this review, we describe the platelet surface molecules with special focus on
      the polymorphic glycoproteins giving rise to the human platelet alloantigen (HPA)
      system. We list the platelet glycoprotein complexes GPIa/IIa, GPIIb/IIIa,
      GPIb/V/IX and some other molecules, the corresponding genes that encode them and
      we describe their polymorphisms as well as their physiological function. Based on
      data obtained by serological and molecular methods, we explain how ancestral HPA
      alloepitopes have developed into the modern variants. We also describe the tissue
      distribution of these proteins, which seems to be wider than thought initially,
      and discuss the significance of the HPA encoding genes distribution in various
      populations. Methods for their determination are then described briefly Since HPA
      alloepitopes can induce antibodies with resulting clinical conditions such as:
      post-transfusion refractoriness to platelets (PTR); post-transfusion
      thrombocytopenic purpura (PTTP); and fetomaternal alloimmune thrombocytopenia
      (FMAIT), the mechanism of this alloimmunization and its prevention is described.
      Although the humoral arm is more important from the clinical viewpoint, the
      activation of the cytotoxic arm by HPA alloepitopes is also possible. These
      polymorphisms also seem to have a role in certain other clinical circumstances,
      therefore their impact on cardiovascular diseases and haemostatic disorders as
      well as their role in the transplantation of solid organs and bone marrow is
      addressed. We conclude that during the last decades, the research of the platelet
      membrane molecules contributed considerably to the diagnostics, prevention and
      therapy of the blood coagulation and haemostatic disorders, to the management of
      the neonatal thrombocytopenias, transfusion-related thrombocytopenias,
      refractoriness to platelet transfusions and autoimmune disorders. It also changed
      our view on the role of HPA alloepitopes in bone marrow and solid organ
      transplantation. In the future, this accumulated knowledge will be useful for the
      development of the cell-based therapies and immune modulation of both acquired
      and hereditary diseases.

PMID- 12216948
TI  - Immunological aspects of blood transfusions.
AB  - Almost all identified acute and/or severe immunological reactions towards blood
      transfusions, reported by surveillance systems such as SHOT (Severe Hazards of
      Transfusion) in the UK are mediated by allo-antibodies. In contrast, the clinical
      effects of transfusion-induced cellular immunity are virtually unknown. Although
      alterations in lymphocyte responses and natural killer cell functions after blood
      transfusion has been reported in many publications, the relevance of these in
      vitro assays for in vivo immunity are lacking. Even for clinically obvious
      immunomodulatory effect of blood transfusions, such as the mitigation of renal
      graft rejection, no uniform in vitro explanation has been identified. In the
      laboratory animal it has been shown that when two antigenic stimuli are given
      simultaneously, the response to one of these antigens is often decreased. Blood
      transfusions introduce a multitude of foreign antigens. Indeed, immunostimulation
      and suppression by blood transfusions have both been found. Systematic studies on
      immunological side-effects of blood transfusions are hardly available. Since the
      UK and France introduced a transfusion vigilance system, severe immunological
      side-effects such as haemolytic reactions, TRALI (acute lung injury), PTP (post
      transfusion purpura) and graft vs. host disease are registrated in these
      countries and their incidence can be estimated based on the national number of
      transfusions. However, every blood transfusion interferes with the immune system
      of the recipient. The available evidence of harm from immune responses not
      leading to severe transfusion reactions will be discussed.

PMID- 12216949
TI  - Laboratory assays for predicting the severity of haemolytic disease of the fetus
      and newborn.
AB  - Haemolytic disease of the fetus and newborn (HDFN) is characterised by the
      presence of IgG antibodies in the maternal circulation which cause haemolysis in
      the fetus by crossing the placenta and sensitising red cells for destruction by
      macrophages in the fetal spleen. Serological, quantitative and cellular assays
      have all been developed to predict the severity of HDFN. These assays measure
      and/or characterise alloantibodies in the maternal circulation. Quantitative
      assays which accurately measure antibody levels correlate with disease severity
      better than serological assays which are inherently less precise. Nevertheless,
      high antibody levels are found in some cases of mild HFDN and relatively low
      antibody levels are found in some severe cases. This suggests that disease
      severity is influenced by factors in addition to antibody concentration. These
      factors remain to be fully elucidated but may include: the subclass and
      glycosylation of maternal antibodies; the structure, site density, maturational
      development and tissue distribution of blood group antigens; the efficiency of
      IgG transport to the fetus; the functional maturity of the fetal spleen;
      polymorphisms which affect Fc receptor function; and the presence of HLA-related
      inhibitory antibodies. Cellular assays which are sensitive to factors affecting
      antibody function have, therefore, been developed in an attempt to improve the
      prediction of disease severity. Although these assays are cumbersome, there are
      now sufficient data to suggest that some cellular assays provide clinically
      useful information to complement serological and quantitative assays.

PMID- 12216950
TI  - Monoclonal anti-D development programme.
AB  - Administration of anti-D immunoglobulin to D- women after delivery of a D+ infant
      has dramatically reduced the number of immunised women and cases of haemolytic
      disease of the fetus and newborn. The use of monoclonal anti-D might alleviate
      some of the pressures on maintaining adequate supplies of plasma sourced anti-D.
      Two human monoclonal antibodies, BRAD-3 (IgG1) and BRAD-5 (IgG3), with proven
      activity in in vitro functional (immunological) assays with cells bearing IgG Fc
      receptors (Fc gammaR) were selected for clinical studies. They were prepared by
      purification of IgG secreted by culture of the Epstein-Barr virus-transformed B
      cell lines in hollow fibre bioreactors. The mean half-lives of BRAD-3 and BRAD-5
      in D- subjects were 10.2 and 22.2 days, respectively. The clearance of D+ red
      cells injected into D- subjects was accelerated by prior injection of the
      monoclonal antibodies, both individually and blended (3:1, BRAD-5/BRAD-3). The
      clearance rate was related to the amount of anti-D on the red cells. Clearance of
      the D+ red cells coated with BRAD-3 was more rapid in subjects homozygous for Fc
      gammaRIIIa-F/F158 than in those expressing the Fc gammaRIIIa-V158 allele. The
      subjects were protected from Rh D immunisation. A large multi-centre study
      evaluated the BRAD-3/5 blend for its ability to prevent Rh D immunisation in 95 D
      subjects given 400 microg i.m. 24 h after injection of 5 ml D+ red cells.
      Challenge injections of D+ red cells alone were given 24 and 36 weeks later, and
      blood samples were taken every 4 weeks from the subjects throughout the study for
      detection of anti-D responses. There was one definite and one possible failure of
      protection; in one subject the plasma anti-D level rose from week 12 onwards, and
      in another individual rapid seroconversion was observed at week 28. Considering
      the relatively large dose of red cells and the number of subjects studied, it was
      concluded that the failure rate was much lower than in routine Rh D prophylaxis.
      The responder rate was 13% by week 36 and 24% by week 48. There was no
      relationship between HLA haplotype and Rh D immunisation. The low percentage of
      responders and the modest levels of endogenous anti-D produced suggested that
      administration of monoclonal anti-D had induced long-term specific suppression of
      anti-D responses in these subjects. The most likely mechanism of action was
      considered to be inhibition of B cells resulting from co-cross-linking antigen
      receptors with inhibitory Fc gammaR when the B cells contacted red cells that had
      bound passive anti-D.

PMID- 12216951
TI  - The role of in vitro alloreactive T-cell functional tests in the selection of HLA
      matched and mismatched haematopoietic stem cell donors.
AB  - Acute graft vs. host (GVH) disease and graft rejection are most frequently caused
      by undetected or disregarded genetically based disparities between the donor and
      recipient of bone marrow derived haematopoietic stem cells (HSC).
      Incompatibilities in extremely polymorphic human leukocyte antigens (HLA), and in
      certain cases also minor histocompatibility antigens, represent the most
      important driving force of such unwanted events, threatening the successful
      outcome of haematopoietic stem cell transplantation (HSCT). The complexity of HLA
      polymorphism can be precisely and elegantly detected at the genomic level by
      several polymerase chain reaction (PCR) based techniques that have strongly
      backed up its predecessor, the far less informative classical serological typing.
      By applying these modern technologies, we gain the deepest insight into HLA
      allelic specificities and thus the possibility to, for example, trace and recruit
      unrelated histocompatible donors for a given patient. In the case when
      exclusively related intrafamilial HSC donors are being considered, we are
      confined to the fact that only 25-30% of patients can expect a completely HLA
      identical donor to be found within core or extended family members. The number of
      related as well as unrelated donors can be increased if certain HLA mismatches
      are accepted. When doing so, the precise definition of disparate
      histocompatibilty antigens between the patient and a possible donor should be
      carried out. But this does not give us the information about the functional
      immunogenicity of such differences. Therefore, in vitro functional assays,
      quantitating the alloreactive potential of lymphocyte T subsets, the central
      immunocompetent cells, are more than necessary. By evaluating mixed lymphocyte
      reaction (MLR), the analysis of helper T cell precursor (HTLp) and cytotoxic T
      cell precursor (CTLp) frequencies, the allogeneic impact of class II and class I
      HLA mismatches between a donor and graft recipient can be assessed and permissive
      disparities defined.

PMID- 12216952
TI  - Selection of unrelated bone marrow donors by serology, molecular typing and
      cellular assays.
AB  - As compared to hematopoietic stem cell transplantation (HSCT) with HLA
      genotypically identical donors, phenotypically matched unrelated HSCT is
      associated with lower survival. Serologically undisclosed HLA disparities account
      for the increased rate of post-transplant complications. With more than 1300
      alleles currently identified, high-resolution molecular typing techniques have to
      be applied to distinguish the extensive degree of allelic polymorphism of the HLA
      system. Whereas a HLA-ABDR-serologically identical donor can be identified in the
      International Registry for >90% of the patients, only half of them can benefit of
      a highly compatible donor if donor selection is based on allele level matching
      for HLA-A/B/Cw/DRB1/B3/B5/DQB1 loci. During the last 10 years, we identified only
      approximately 20% of all known HLA alleles in the searches for our mainly
      Caucasoid patients. Rare alleles (i.e. alleles that represent <1% of a given
      serotype) do not have a major impact in patient/donor matching. Most of the
      incompatibilities are clustered in a limited number of serotypes that can be
      targeted first during the searches. However, due to linkage disequilibrium (e.g.
      B-Cw or DRB1-DQB1), incompatibilities at a given locus are often associated with
      disparities at adjacent loci. In vitro cellular assays such as the cytotoxic T
      lymphocyte precursor frequency (CTLpf) analysis may contribute in discriminating
      functionally relevant HLA class I disparities, as well as minor antigen
      mismatches in case of sensitized donors. When a rare variant or an uncommon
      association in the patient's HLA haplotype has been found, the tissue typing
      laboratory may recommend considering a mismatched donor early in the search
      procedure instead of continuing a search with a low probability of success.

PMID- 12216953
TI  - Immunogenetic selection of donors for haematopoietic stem cell transplantation:
      an approach.
AB  - Histocompatibility between the patient and his donor is a prerequisite for the
      success of transplantation of haematopoietic stem cells (HSCT).
      Histocompatibility testing is clinically performed by HLA typing. HLA typing can
      be highly informative if performed in families. In this case, comparatively
      little typing effort often allows to predict the identity of whole HLA
      haplotypes. HLA typing becomes more demanding, however, if unrelated individuals
      have to be considered as donors. Given the huge diversity of HLA molecules the
      answer to the question, whether patient and donor possess 'matched' HLA types
      requires considerable typing effort. Interaction between the HLA typing
      laboratory and the clinician is highly needed. It has to be agreed upon what loci
      are considered relevant and what degree of resolution is necessary. Furthermore,
      a strategy has to be developed, which ensures that a maximum of potential donors
      are tested in a reasonable time frame avoiding at the same time a work-overload
      of the laboratory and an excessive uneconomical typing effort. At present,
      experience with HSCT with unrelated donors is limited. So there is no consent on
      the 'correct' way of choosing unrelated donors. Each transplantation centre will
      have its own characteristic needs, resources, manpower and skills; therefore, the
      ways vary between centres. I want to present the approach in Vienna.

PMID- 12216954
TI  - Computer applications in the search for unrelated stem cell donors.
AB  - The majority of patients which are eligible for a blood stem cell transplantation
      from an allogeneic donor do not have a suitable related donor so that an
      efficient unrelated donor search is a prerequisite for this treatment. Currently,
      there are over 7 million volunteer donors in the files of 50 registries in the
      world and in most countries the majority of transplants are performed from a
      foreign donor. Evidently, computer and communication technology must play a
      crucial role in the complex donor search process on the national and
      international level. This article describes the structural elements of the donor
      search process and discusses major systematic and technical issues to be
      addressed in the development and evolution of the supporting telematic systems.
      The theoretical considerations are complemented by a concise overview over the
      current state of the art which is given by describing the scope, relevance,
      interconnection and technical background of three major national and
      international computer appliances: The German Marrow Donor Information System
      (GERMIS) and the European Marrow Donor Information System (EMDIS) are
      interoperable business-to-business e-commerce systems and Bone Marrow Donors
      World Wide (BMDW) is the basic international donor information desk on the web.

PMID- 12216955
TI  - The complexity of immune and alloimmune response.
AB  - Alloimmune response induced by foreign histoincompatible alloantigens is a
      complex phenomenon possessing mechanisms, characteristics to innate and adoptive
      immune response. It is also modified by various immunregulating exocrine and
      autocrine factors. Starting the new time period of functional genomics the
      knowledge of human genes' structure needs a more clear insight not only about the
      function and contribution of genes but their historical background, origin and
      importance in the phylogenesis. Comparative immunology comes into focus of
      interest helping to understand the complexity of immune and alloimmune response.
      It is almost unbelievable that immune functions as phagocytosis and cytokine
      production like IL-1 and TNF have already emerged 700 million years ago in
      starfishes and sponges. Functions--including recruitment of coelomocytes, killing
      of micro-organisms by lysosome-like enzyme activity, opsonization by complement
      analogous proteins and oxidative burst function--remained unchanged during
      phylogenesis and could be found not only in insects but in mammals as well as
      representatives of innate immunity. The importance of these molecules is
      reflected in homology of conservative regions. One of the biggest evolutionary
      steps happened 500 million years ago when fish developed a jaw in the Placoderms
      species. This fact led to the development of gut associated immune system. The
      system was the basis to create the genetic material for recombination and
      mutation to establish variability and diversity of proteins, as immunoglobulins.
      It is interesting to lean how diversity of immunglobulins in sharks is insured by
      joining of blocks of V, D, J and C genes, in contrast to humans, where those
      genes are located on different chromosome regions. These differences are
      associated with an immediate production of specific immunglobulin or a slower one
      combined with immunologic memory. Similar development could be found in T cell
      antigen specific receptors, too. Concerning the establishment of adoptive
      immunity by emergence of genetic recombination, which allowed the production of a
      huge diversity of specific antigen binding proteins, another structure developed
      parallel from the histoglobin molecule. This protein was created to catch peptide
      particles which split from the proteins originating from microorganisms, viruses
      or foreign cell compartments. The cave-like groove capturing the different
      peptides represented a huge variability. These histocompatibility molecules
      emerged from this ancient structure for more than 300 million years ago. The
      genetic family responsible for their synthesis became the most complex gene
      family including many other genes involved in the immune response. The
      polymorphic character of the histocompatibility protein is responsible for the
      capture of the relevant peptides fitting best to the allotype-determined groove.
      In certain species the same function could be filled by different ancient
      molecules with the same success. Dendritic cells and their importance in
      differentiation and antigen presentation became in the focus of interest in the
      last decade. They have lymphoid and myeloid origin, mature and less
      differentiated subtypes with characteristic CD markers and cytokine profile.
      Their function and origin from the stem cell subpopulation is an important
      example how nature influences the development of immunity to the accommodation
      and survival to the always changing environment. The new molecular techniques
      will help to get closer to understand the function of genes regulating immune
      response and modify them.

PMID- 12216956
TI  - Increasing amounts of dietary myristic acid modify the plasma cholesterol level
      and hepatic mass of scavenger receptor BI without affecting bile acid
      biosynthesis in hamsters.
AB  - The purpose of this study was to analyze the effects of increasing amounts of
      dietary myristic acid (0.03 to 4.2% of the total dietary energy) on the plasma
      and hepatic cholesterol metabolism. Six groups of hamsters received semi-purified
      diets containing 0.05% cholesterol and 12.5% lipids and differing only by the
      nature of the triglycerides (Safflower oil, lard, lard/coconut oil (1:1), milk
      fat, milk fat/coconut oil (1:1), coconut oil) for 3 weeks. A positive regression
      between the plasma cholesterol level and the dietary myristic acid level was
      observed (r = 0.60, P < 0.0001). However, it is noteworthy that the increase in
      plasma total cholesterol only reflects an increase in the level of HDL
      cholesterol. In parallel, the mass SR-BI decreased linearly with the increased
      level of myristic acid in the diet, whereas the LDL-R did not change. This study
      shows that increasing amounts of myristic acid (0.03 to 4.2%) do not alter the
      cholesterol or bile acid metabolism and increase only the HDL-C.

PMID- 12216957
TI  - Transgenesis for the study and the control of lactation.
AB  - The study and the control of milk synthesis are required to decipher the
      mechanisms of gene expression, to improve milk production, to modify milk
      composition, to induce a resistance to diseases in the mammary gland and to
      produce recombinant proteins of pharmaceutical interest. Transgenesis has become
      a mandatory tool to reach these goals. The use of transgenesis is still limited
      by the difficulty of adding foreign genes in farm animals and mainly by replacing
      genes by homologous recombination. Transgene expression is also often ill
      controlled. The present paper summarizes the current progress in this field with
      a particular emphasis on expression vectors for transgenes.

PMID- 12216959
TI  - Potential uses of milk epithelial cells: a review.
AB  - Secretions collected from the mammary gland of different species contain
      heterogeneous populations of cells including lymphocytes, neutrophils,
      macrophages and epithelial cells in different species. Several factors influence
      the somatic cell count in milk and the distribution of cell types, such as
      species, infection status, physiological status and management practices. The
      epithelial cells are shed into milk during the lactation process. Most of them
      are viable and exhibit the characteristics of fully differentiated alveolar
      cells. Primary cultures of epithelial cells from colostrum and milk of humans,
      baboons, cows and goats together with established cell lines from human and goat
      milk, provide a good model for the study of lactogenesis, immunity transmission,
      cancer research and infection by viruses. The RNA extracted from milk cells have
      been shown to be representative of gene expression in the mammary gland and thus
      provide a source of material for molecular studies of gene expression and
      environmental interactions.

PMID- 12216958
TI  - Lowering the milk lactose content in vivo: potential interests, strategies and
      physiological consequences.
AB  - Lactose is the major sugar present in milk and an important osmotic regulator of
      lactation. It is digested by intestinal lactase, an enzyme expressed in new
      borns. Its activity declines following weaning. As a result, adult mammals are
      normally lactose-intolerant and more than 75% of the human adult population
      suffers from lactase deficiency. A reduction in milk lactose content could be
      beneficial for nutritional but also agricultural and industrial purposes (less
      volume to transport, better milk coagulation, less effluent production). Several
      attempts to create transgenic mice producing milk with modified carbohydrate
      compositions have recently been described. Depending on whether these
      modifications resulted from an alteration of lactose synthesis or from lactose
      hydrolysis, striking physiological differences are observed.

PMID- 12216960
TI  - Milk lipid and protein traffic in mammary epithelial cells: joint and independent
      pathways.
AB  - In mammary epithelial cells, milk lipids and proteins are synthesised in the same
      compartment, the endoplasmic reticulum. Lipids, carried through the cytoplasm,
      associate with the apical membrane which then pinches off and releases the lipid
      globule. Proteins, carried through membrane compartments are released in the
      lumen after fusion of secretory vesicles with the apical membrane. These
      processes assure a relatively constant composition of milk but it is not known
      whether lipid and protein secretion are linked. The protein composition of the
      milk fat globule membrane and the stimulatory effects of prolactin and oxytocin
      on lipid and protein secretion suggest that these processes are coupled and co
      regulated. However, it is possible to observe a dissociation between the
      formation and the secretion of the two constituents, during differentiation and
      in various experimental conditions, and this suggests that coupling is not
      strictly required.

PMID- 12216961
TI  - Is the apocrine milk secretion process observed in the goat species rooted in the
      perturbation of the intracellular transport mechanism induced by defective
      alleles at the alpha(s1)-Cn locus?
AB  - The structural and quantitative variability of caprine alpha(s1)-casein induced
      by the extensive polymorphism recorded at the corresponding locus strongly
      influences the composition (proteins as well as lipids) and the technological
      behaviour of milk. Immuno-histo-chemistry studies coupled with electron
      microscopy analysis have shown that a dysfunction exists in the intracellular
      transport of caseins when alpha(s1)-casein is lacking. Casein accumulation in the
      endoplasmic reticulum leads to a dilation of the cisternae that could disturb the
      whole secretion process (including lipids). Despite a long controversy, goat milk
      secretion is still considered to occur through an apocrine process contrary to
      the merocrine process described for cow's milk. We suggest that the apocrine
      pathway of secretion described in the goat could be the consequence of the
      dysfunction observed in the intracellular transport of caseins when alpha(s1)
      casein is lacking. To obtain further clues in the favour of such a hypothesis, we
      compared the protein and lipid fractions of milks from goats homozygous for
      different alpha(s1)-casein alleles.

PMID- 12216962
TI  - Oxytocin and milk removal: two important sources of variation in milk production
      and milk quality during and between milkings.
AB  - This review describes the effects of milking (routine and management) on milk
      yield and milk quality on dairy ruminants and examines the physiological effects
      of milking on the synthesis and secretion of milk. During milking, differences in
      the composition of milk as a result of milk ejection reflex are observed: the
      cisternal milk, immediately available, contains little fat, then milk ejection
      provokes active transport of high-fat content alveolar milk, into the cisternal
      compartment. Milking frequency has the capacity to affect milk production too.
      So, an increase in milking frequency augments milk yield whereas a decrease in
      milking frequency decreases milk production, with effects on milk composition.
      The milk ejection reflex is mediated by oxytocin, which induces myoepithelial
      cell contraction. Nevertheless, other actions of oxytocin may exist, such as a
      direct effect on proliferation and differentiation of myoepithelial cells and on
      secretory processes in the mammary epithelial cells.

PMID- 12216964
TI  - Occupational orthopaedics: raising public awareness.

PMID- 12216963
TI  - Dietary trans-vaccenic acid (trans11-18:1) increases concentration of
      cis9,transll-conjugated linoleic acid (rumenic acid) in tissues of lactating mice
      and suckling pups.
AB  - Lactating mice were fed trans-vaccenic acid (trans 11-18:1, TVA) to assess
      desaturation of TVA to cis9,trans11-conjugated linoleic acid (9/11CLA). Diets
      contained 30 g x kg(-1) 18:2n-6 (LA) or 20 g LA plus 10 g 18:0 (SA), TVA, or a
      CLA mixture (MCLA). Compared with SA, feeding TVA increased 9/11CLA
      concentrations in blood plasma phospholipid, triglyceride, and free fatty acid
      fractions. However, concentrations of 9/11CLA in plasma fractions were greater
      when MCLA was fed compared with SA or TVA. No 9/11CLA was detected in liver of
      mice fed SA, and it was only 1 mg x g(-1) of total fatty acids in the carcass. In
      contrast, 9/11CLA content of liver (5 mg x g(-1)) and carcass (6 mg x g(-1)) of
      mice fed TVA was similar to liver (5 mg x g(-1)) and carcass (7 mg x g(-1)) of
      mice fed MCLA. Mammary tissue of SA-fed mice had no detectable 9/11 CLA, compared
      with 5 or 14 mg x g(-1) for TVA or MCLA-fed mice. Stearoyl-CoA desaturase
      activity in mammary tissue from TVA-fed dams was 14% greater compared with SA.
      Activity of this enzyme in liver tissue was similar among treatments. In pups
      nursing TVA-fed dams, 9/1 ICLA accounted for 3 mg x g(-1) in liver but no 9/11CLA
      was detected in the carcass. In pups nursing MCLA-fed dams, however, 9/11CLA
      accounted for 8 and 6 mg x g(-1) in liver and carcass. Results indicated TVA
      desaturation enhanced 9/11CLA in tissues and milk fat.

PMID- 12216965
TI  - Efficacy of celecoxib versus ibuprofen in the treatment of acute pain: a
      multicenter, double-blind, randomized controlled trial in acute ankle sprain.
AB  - Ankle sprain is a common acute soft-tissue injury that often results in pain,
      inflammation, and ecchymosis. In this multicenter, double-blind, randomized
      parallel-group study, 445 adult patients received celecoxib 400 mg/day, ibuprofen
      2,400 mg/day, or placebo for 10 days. Patients had experienced grade 1 or 2 ankle
      sprains within 48 hours and had moderate to severe ankle pain. Patient's Global
      Assessment of Ankle Injury responses, given on days 4 and 8, showed that the
      celecoxib group improved significantly more than the placebo group did, with 67%
      of the celecoxib group versus 55% of the placebo group improving at day 4 (P <
      .05). Patient's Assessment of Ankle Pain Visual Analog Scale on Weight Bearing
      responses, also given on days 4 and 8, showed that celecoxib was as efficacious
      in the treatment of ankle sprain as the maximum therapeutic dosage of ibuprofen
      and that, compared with placebo, it reduced pain significantly more (P < .05).
      The celecoxib group recovered and returned to function earlier (after 5 days)
      than did either the placebo group (8 days) or the ibuprofen group (6 days); the
      celecoxib-placebo difference was significant. Celecoxib, a cyclo-oxygenase-2
      specific inhibitor with platelet-function-sparing properties, may be useful as a
      multimodal adjuvant in the treatment of ankle sprain.

PMID- 12216966
TI  - Congenital absence of the long head of the biceps brachii tendon as a VATER
      association.
AB  - Absence of the long head of the biceps brachii tendon is rare (only 1 case
      reported). We believe that our article is the first to report this anomaly as
      associated with VATER complex (vertebral defects, anal atresia, tracheoesophageal
      fistula with esophageal atresia, and radial and renal anomalies).

PMID- 12216967
TI  - Nonunion of a scapula body fracture in a high school football player.
AB  - We report the case of a 16-year-old boy who sustained a minimally displaced
      fracture of the inferior angle of the scapula during a high school football game.
      This fracture progressed to symptomatic nonunion and persistent pain. Treatment
      included curettage of loose, fibrous tissue interposed at the fracture site;
      fragment excision; range-of-motion exercises started early in the postoperative
      period, and progressive scapula strengthening. Four and a half months after
      initial injury, the patient returned to all activities and was asymptomatic.

PMID- 12216968
TI  - Os acromiale.

PMID- 12216969
TI  - Assessment and classification of bone stock deficiency in revision total hip
      arthroplasty.
AB  - It is critical for appropriate treatment choices in revision total hip
      arthroplasty that bone stock deficiency be assessed and classified. Acetabular
      and femoral defects must be separately assessed, although a combined assessment
      is needed at the time of surgery to select the appropriate match of components
      for a given patient. Classification systems help surgeons predict defects and
      determine reconstruction planning prior to surgery. This article presents the
      senior author's classification of acetabular and femoral defects for revision
      total hip arthroplasty.

PMID- 12216970
TI  - Extensively porous-coated femoral stems in revision hip arthroplasty: rationale
      and results.
AB  - Optimal outcomes of revision femoral arthroplasty include achieving rotational
      stability of the revision implant, preventing axial migration of the implant to
      obtain stability, and reproducing normal hip biomechanics. Cemented and
      proximally porous-coated implants are not well-suited to achieving these goals in
      the presence of metaphyseal bone defects and poor endosteal cement bonding.
      Extensively porous-coated implants are more likely to achieve these goals if the
      selection of the implant is appropriate for each defect encountered and if
      technical problems can be identified that may arise during canal preparation
      andcomponent insertion. The selection of curved implants for longer revisions may
      help avoid complications.

PMID- 12216971
TI  - Removal of well-fixed femoral and acetabular components.
AB  - One of the more difficult procedures in revision total hip arthroplasty is
      removal of a well-fixed femoral stem or acetabulum. Techniques to remove well
      fixed, fully coated implants (cemented or uncemented) are discussed here. Results
      of these techniques show that operative time can be decreased and femoral and
      pelvic bone loss can be minimized, making a complicated revision more
      straightforward.

PMID- 12216972
TI  - Cemented cup revisions.
AB  - Among the several treatment techniques for acetabular reconstruction after total
      hip arthroplasty is cemented acetabular revision. Use of isolated cemented cup
      revision is not frequently chosen for acetabular revision, however, because
      outcomes with this technique are poor despite improved cementing techniques. Most
      cemented cup revisions are performed for severe bone loss when biologic fixation
      near the normal hip center is unlikely and are often supplemented with bone
      grafting and metal reinforcement devices cases. Advantages of using this
      technique are the ability to incorporate antibiotics into the cement and the
      ability to customize the cement mantle to host bone.

PMID- 12216973
TI  - Structural acetabular allograft in revision total hip arthroplasty.
AB  - Structural allografts are a surgical option only in cases of severe bone loss.
      Structural allografting techniques have been developed to fill large bony defects
      and can be used to provide structural support and reconstitute bone stock.
      Superior dome allografts are utilized when 50% or more of host bone is available
      for contact with the ingrowth cup. In revision surgery where the allograft
      supports more than 50% of the reconstruction, complications are more common.
      Although good results are reported, implant failure and graft resorption are more
      commonly seen. The addition of a reconstruction ring to the reconstruction
      unloads some of the stress applied to the allograft. In these cases, superior
      results have been reported.

PMID- 12216974
TI  - Complications of total hip arthroplasty.
AB  - Complications following hip arthroplasty have a wide variation and range in
      incidence from 1.1% for pulmonary embolism to over 70% for infrapopliteal deep
      vein thrombosis. Recognition of the risk factors and all of the possible types of
      complications places the surgeon in a better position to detect such
      complications and formulate a plan to treat them. This article documents some
      ofthe complications that can occur during or after surgery following hip surgery.
      These complications are stratified as systemic and procedure specific.

PMID- 12216975
TI  - Molecular analyses of the principal components of response strength.
AB  - Killeen and Hall (2001) showed that a common factor called strength underlies the
      key dependent variables of response probability, latency, and rate, and that
      overall response rate is a good predictor of strength. In a search for the
      mechanisms that underlie those correlations, this article shows that (a) the
      probability of responding on a trial is a two-state Markov process; (b) latency
      and rate of responding can be described in terms of the probability and period of
      stochastic machines called clocked Bernoulli modules, and (c) one such machine,
      the refractory Poisson process, provides a functional relation between the
      probability of observing a response during any epoch and the rate of responding.
      This relation is one of proportionality at low rates and curvilinearity at higher
      rates.

PMID- 12216976
TI  - Observing behavior: effects of rate and magnitude of primary reinforcement.
AB  - Four experiments examined the free-operant observing behavior of rats. In
      Experiment 1, observing was a bitonic function of random-ratio schedule
      requirements for the primary reinforcer. In Experiment 2, decreases in the
      magnitude of the primary reinforcer decreased observing. Experiment 3 examined
      observing when a random-ratio schedule or a yoked random-time schedule of primary
      reinforcement was in effect across conditions. Removing the response requirement
      for the primary reinforcer increased observing, suggesting that the effects of
      the random-ratio schedule in Experiment 1 likely were due to an interaction
      between observing and responding for the primary reinforcer. In Experiment 4,
      decreasing the rate of primary reinforcement by increasing the duration of a
      random-time schedule decreased observing monotonically. Overall, these results
      suggest that observing decreases with decreases in the rate or magnitude of the
      primary reinforcer, but that behavior related to the primary reinforcer can
      affect observing and potentially affect measurement of conditioned reinforcing
      value.

PMID- 12216977
TI  - Group foraging sensitivity to predictable and unpredictable changes in food
      distribution: past experience or present circumstances?
AB  - The ideal free distribution theory (Fretwell & Lucas, 1970) predicts that the
      ratio of foragers at two patches will equal the ratio of food resources obtained
      at the two patches. The theory assumes that foragers have "perfect knowledge" of
      patch profitability and that patch choice maximizes fitness. How foragers assess
      patch profitability has been debated extensively. One assessment strategy may be
      the use of past experience with a patch. Under stable environmental conditions,
      this strategy enhances fitness. However, in a highly unpredictable environment,
      past experience may provide inaccurate information about current conditions.
      Thus, in a nonstable environment, a strategy that allows rapid adjustment to
      present circumstances may be more beneficial. Evidence for this type of strategy
      has been found in individual choice. In the present experiments, a flock of
      pigeons foraged at two patches for food items and demonstrated results similar to
      those found in individual choice. Experiment 1 utilized predictable and
      unpredictable sequences of resource ratios presented across days or within a
      single session. Current foraging decisions depended on past experience, but that
      dependence diminished when the current foraging environment became more
      unpredictable. Experiment 2 repeated Experiment I with a different flock of
      pigeons under more controlled circumstances in an indoor coop and produced
      similar results.

PMID- 12216979
TI  - Navigation in the Morris swim task as a baseline for drug discrimination: a
      demonstration with morphine.
AB  - A morphine versus saline discrimination was demonstrated using the Morris swim
      task as the behavioral baseline. The apparatus was a large circular pool filled
      with water made opaque by floating polypropylene pellets. Rats were placed in the
      tank in randomly selected locations (12 trials per session) and could escape by
      swimming to a platform submerged 2 cm below the surface. Morphine (5.6 mg/kg) or
      saline was injected prior to training sessions. The position of the platform in a
      given session depended on the drug condition, thus forming the basis for
      discriminative responding. Three of the 4 rats acquired the discrimination, as
      evidenced by direct swims to the condition-appropriate platform. Generalization
      probe sessions were conducted following acquisition. Probe sessions were preceded
      by injections of morphine (0, 1.0, 3.0, 5.6, or 10.0 mg/kg) and involved placing
      the rat in the pool for 1 min without a platform. Swim patterns revealed a
      gradient, with probe swimming more concentrated in the area of the morphine
      platform position after higher morphine doses. In addition, dose-dependent
      increases in the likelihood of swimming first to the morphine-associated platform
      location were obtained. These results illustrate the generality of drug
      discrimination across different behavioral procedures, and of particular interest
      with respect to spatial learning, demonstrate interoceptive stimulus control of
      navigation.

PMID- 12216978
TI  - Effects of D-amphetamine in a temporal discrimination procedure: selective
      changes in timing or rate dependency?
AB  - Two experiments evaluated rate dependency and a neuropharmacological model of
      timing as explanations of the effects of amphetamine on behavior under
      discriminative control by time. Four pigeons pecked keys during 60-trial
      sessions. On each trial, the houselight was lit for a particular duration (5 to
      30 s), and then the key was lit for 30 s. In Experiment 1, the key could be lit
      either green or blue. If the key was lit green and the sample was 30 s, or if the
      key was lit blue and the sample was 5 s, pecks produced food on a variable
      interval 20-s schedule. The rate of key pecking increased as a function of sample
      duration when the key was green and decreased as a function of sample duration
      when the key was blue. Acute d-amphetamine (0.1 to 3.0 mg/kg) decreased higher
      rates of key pecking and increased lower rates of key pecking as predicted by
      rate dependency, but did not shift the timing functions leftward (toward
      overestimation) as predicted by the neuropharmacological model. These results
      were replicated in Experiment 2, in which the key was lit only one color during
      sessions, indicating that the effects were not likely due to disruption of
      discriminative control by key color. These results are thus consistent with rate
      dependency but not with the predictions of the neuropharmacological model.

PMID- 12216980
TI  - From development to evolution: the re-establishment of the "Alexander Kowalevsky
      Medal".
AB  - The Saint Petersburg Society of Naturalists has reinstated the Alexander O.
      Kowalevsky Medal. This article announces the winners of the first medals and
      briefly reviews the achievements of A.O. Kowalevsky, the Russian comparative
      embryologist whose studies on amphioxus, tunicates and germ layer homologies
      pioneered evolutionary embryology and confirmed the evolutionary continuity
      between invertebrates and vertebrates. In re-establishing this international
      award, the Society is pleased to recognize both the present awardees and the
      memory of Kowalevsky, whose work pointed to that we now call evolutionary
      developmental biology.

PMID- 12216981
TI  - The ontogeny of allorecognition in a colonial hydroid and the fate of early
      established chimeras.
AB  - Colonies of the marine hydroid, Hydractinia, are able to discriminate between
      their own tissues and those belonging to unrelated conspecifics. We have studied
      the ontogeny of this allorecognition system by a series of allogeneic
      transplantations along a developmental gradient, including two-cell-stage
      embryos, 8 h morulae, planula larvae and metamorphosed polyps. Allograft
      acceptance of incompatible tissue was observed in all embryonic and larval
      stages, whereas metamorphosed polyps rejected incompatible transplanted
      allografts. Most of the chimeras established at the two-cell-stage, although
      composed of two allogeneic, incompatible entities with mismatching
      allorecognition loci, developed normally and remained stable through
      metamorphosis. The results of post metamorphic transplantation assays among the
      chimeras and the naive ramets, suggested that both incompatible genotypes were
      still represented in the chimera despite the onset of alloimmune maturation. The
      naive colonies always rejected each other. Chimeras established from later
      embryonic and larval stages did not develop into adult chimeric entities, but
      rather separated immediately post metamorphosis. We thus show that (1)
      allorecognition in this species matures during metamorphosis and (2) genetically
      incompatible entities may coexist in one immunologically mature, chimeric soma,
      provided that they were grafted early enough in ontogeny.

PMID- 12216982
TI  - Ca2+-ions and pattern control in Hydra.
AB  - The fresh water polyp Hydraforms buds which develop a foot at their base and
      separate from the parent. In the strain H. vulgaris (Zurich), various compounds
      including phorbolesters, diacylglycerols, cantharidin and Li+-ions were found to
      prevent foot formation at the bud's base. Therewith, the bud transforms into a
      branch which persists at the parent. Other strains were found to be unaffected by
      such treatments. Here we show that a reduced Ca2+-ion concentration of the
      culture medium causes branch formation in the H. vulgaris (Zurich) strain but not
      in the other strains tested. However, all strains tested transformed their buds
      into branches when the medium was enriched with Ba2+ and Sr2+ ions. We suggest
      that the various treatments either reduce the internal concentration of Ca2+-ions
      by stimulating Ca2+-ion export or compete with Ca2+-ions at theirtarget. H.
      vulgaris (Zurich) isthe most sensitive strain tested and appears to have the most
      efficient Ca2+-pumps. This appears to be necessary forthese animals derived from
      a lake which is extremely rich in Ca2+ ions.

PMID- 12216984
TI  - Differentiation and growth of kype skeletal tissues in anadromous male Atlantic
      salmon (Salmo salar).
AB  - The re-initiation of bone development in adult starving Atlantic salmon (Salmo
      salar) during their energetically expensive upstream migration is remarkable and
      deserves closer examination. Dramatic alterations of the skull bones and teeth,
      most prominently, the development of a kype in males, are widely known but little
      studied or understood. We describe the microstructure and the cellular processes
      involved in the formation of the skeletal tissues of the kype. Fresh bone
      material, obtained from animals migrating upstream was subjected to radiological,
      histological or histochemical analysis. We show that the kype is, in part,
      composed of rapidly growing skeletal needles arising at the tip of the dentary.
      Proximally, the needles anastomose into a spongiosa-like meshwork which retains
      connective tissue inside bone marrow spaces. Ventrally, the needles blend into
      Sharpey fiber bone. Skeletal needles and Sharpey fiber bone can be distinguished
      from the compact bone of the dentary by radiography. Rapid formation of the
      skeleton of the kype is demonstrated by the presence of numerous osteoblasts, a
      broad distal osteoid zone, and the appearance of proteoglycans at the growth
      zone. The mode of bone formation in anadromous males can be described as 'making
      bone as fast as possible and with as little material as possible'. Unlike the
      normal compact bone of the dentary, the new skeletal tissue contains chondrocytes
      and cartilaginous extracellular matrix. Formation of the skeleton of the kype
      resembles antler development in deer (a form of regeneration), or hyperostotic
      bone formation in other teleost fishes, rather than periosteal bone growth. The
      type of boneformation may be understandable in the light of the animals'
      starvation and the energetic costs of upstream migration. However, the structured
      and regulated mode of bone formation suggests that the skeleton of the kype has
      functional relevance and is not a by-product of hormonal alterations or change of
      habitat.

PMID- 12216983
TI  - Sex reversal of genetic females (XX) induced by the transplantation of XY somatic
      cells in the medaka, Oryzias latipes.
AB  - In order to investigate the function of gonadal somatic cells in the sex
      differentiation of germ cells, we produced chimera fish containing both male (XY)
      and female (XX) cells by means of cell transplantation between blastula embryos
      in the medaka, Oryzias latipes. Sexually mature chimera fish were obtained from
      all combinations of recipient and donor genotypes. Most chimeras developed
      according to the genetic sex of the recipients, whose cells are thought to be
      dominant in the gonads of chimeras. However, among XX/XY (recipient/donor)
      chimeras, we obtained three males that differentiated into the donor's sex.
      Genotyping of their progeny and of strain-specific DNA fragments in their testes
      showed that, although two of them produced progeny from only XX spermatogenic
      cells, their testes all contained XY cells. That is, in the two XX/XY chimeras,
      germ cells consisted of XX cells but testicular somatic cells contained both XX
      and XY cells, suggesting that the XY somatic cells induced sex reversal of the XX
      germ cells and the XX somatic cells. The histological examination of developing
      gonads of XX/XY chimera fry showed that XY donor cells affect the early sex
      differentiation of germ cells. These results suggest that XY somatic cells start
      to differentiate into male cells depending on their sex chromosome composition,
      and that, in the environment produced by XY somatic cells in the medaka, germ
      cells differentiate into male cells regardless of their sex chromosome
      composition.

PMID- 12216985
TI  - Differential post-transcriptional regulations of wnt mRNAs upon axolotl meiotic
      maturation.
AB  - The products of the Wntgene family play an essential role in several aspects of
      embryo patterning. We have investigated the post-transcriptional regulation of
      three of these genes: Awnt-1, Awnt-5A and Awnt-5B during axolotl (Ambystoma
      mexicanum) oogenesis, oocyte maturation and early development. We show that Awnt
      1, Awnt-5A and Awnt-5B mRNAs are maternally expressed. The three transcripts are
      tightly regulated at specific times and display differential mRNA stability,
      poly(A) tail length and localization. In contrastto Awnt-5Bwhich is restricted to
      the animal hemisphere, Awnt-1 and Awnt-5A have no particular localization in
      stage VI oocytes. Interestingly, these two mRNAs exhibit a polyadenylation
      gradient along the animal-vegetal axis. Moreover, after meiotic maturation, Awnt
      1 and 5A mRNAs become exclusively localized to the animal pole. This isthe first
      evidence of a complete mRNA re-localization to the animal hemisphere during
      oocyte maturation.

PMID- 12216986
TI  - Developmental potential of mouse tetraploid cells in diploid <--> tetraploid
      chimeric embryos.
AB  - Mouse 2n (lacZ-) <--> 4n (lacZ+) aggregation chimeras were examined 5 or 10 days
      after uterine transfer to test the potential of 4n cells to contribute to
      embryonic tissues. Recovered embryos corresponded to embryonic day 7.5
      approximately 8.0 and 12.5, respectively. Ten days after transfer, 4n cells were
      never detected, as reported earlier, in embryonic tissues of chimeras produced by
      the standard procedure in which one 2n embryo at the8-cell stage is aggregated
      with a4n embryo at the4-cell stage. However, beta-gal positive cells were present
      in embryonic tissues, though in a low number, in chimeras produced by a 2n and a
      4n embryo at the 4-cell stage. Similar results were obtained when one 2n embryo
      atthe 8-cell stage was aggregated with two 4n embryos atthe 4-cell stage. beta
      gal positive cells were found in the heart, liver, skin and intestinal
      epithelium. The majority of chimeras 5 days after uterine transfer retained beta
      gal positive cells in embryonic tissues. The complete lack of 4n cell
      contribution to chimeras produced by the standard procedure is therefore
      attributed to the initial low proportion of 4n cells allocated to epiblast and
      their severe elimination from embryonic tissues.

PMID- 12216987
TI  - Myonuclear domain size varies along the lengths of maturing skeletal muscle
      fibers.
AB  - In a skeletal muscle fiber, each myonucleus is responsible for gene expression in
      its surrounding cytoplasm. The region of cytoplasm associated with an individual
      myonucleus is termed myonuclear domain. However, little is known about domain
      size variation within individual muscle fibers. This study tests the hypothesis
      that myonuclear domains expressing neonatal myosin within end regions of maturing
      fibers will be smaller than domains elsewhere in the fibers. The model used is
      chicken pectoralis, where we have previously shown that during development
      repression of neonatal myosin radiates from the central region towards the fiber
      ends. Samples excised from birds aged nine through to 115 days after hatching
      were sectioned transversely. Using computer image analysis and
      immunocytochemistry, fiber profiles were classified as neonatal, transforming or
      adult. Each profile was also located in an adjacent dystrophin-labelled section,
      where myonuclei were visualized using haematoxylin and bisbenzamide. Variation in
      myonuclear length with age was not found to be significant (p = 0.925). Myonuclei
      were counted, and formulae used to calculate mean myonuclear domain size for each
      profile type. Myonuclear number/mm fiber was calculated to be adult (mean =
      108.57 myonuclei/mm), transforming (65.82) and neonatal (25.23). Transforming
      profiles had significantly (p=0.027) more myonuclei/mm than neonatal, as did
      adult (p=0.005). Volume of cytoplasm/myonucleus was adult (mean = 16,132
      microm3/myonucleus), transforming (12,899) and neonatal (8,130). Transforming and
      adult profiles had significantly (p<0.001) larger myonuclear domains than did
      neonatal profiles. Transforming and adult profiles did not differ in either
      myonuclei/mm (p=0.302) or volume of cytoplasm/myonucleus (p=0.413). This study
      demonstrates smaller domains at the terminal tips of maturing muscle fibers.

PMID- 12216988
TI  - Developmental patterning of the circumvallate papilla.
AB  - Organogenesis is regulated by the sequential and reciprocal interactions between
      epithelial and mesenchymal tissues. Many molecules, including growth factors,
      transcription factors, extracellular matrices, cell surface receptors, and matrix
      degrading enzymes, have been found to be involved in this process. To investigate
      the molecular mechanism responsible for morphogenesis of the circumvallate
      papilla/von Ebners' gland complex, we examined the expression patterns of
      selected cell adhesion molecules, extracellular matrix molecules, innervation and
      cell division in the circumvallate papilla of mouse embryos from embryonic day
      11.5 (E11.5) to E14. At E11.5-E13.5, the lingual epithelium, the site where the
      circumvallate papilla will develop, is negative for BrdU labeling. At E14-E15, we
      detected cell division in the papillary area, especially in the epithelial
      invagination where von Ebners' minor salivary gland will form. The basement
      membrane component, laminin, is expressed as a continuous thin line separating
      the epithelia from the underlying mesenchyme, but it is broadly and strongly
      expressed in the area wherethe nervefibers penetrate into the circumvallate
      papilla. At the E12-E12.5 stage of development, the epithelial thickening shows
      intense E-cadherin staining in the superficial and basal layers, but weak E
      cadherin staining in the suprabasal layer. E-cadherin is strongly expressed, but
      appears dispersed among the basal layer of lingual epithelium, the site where
      nerve fibers will innervate. At E13, nerve fibers reach the circumvallate
      papilla. These nerve fibers penetrate into and split the epithelial cell mass
      into two stalks which will later differentiate to form the von Ebners' gland.
      These results suggest that 1) the formation of the circumvallate papilla does not
      initially depend on cell division, 2) cell migration likely plays a major role
      during circumvallate placode formation, 3) E-cadherin and laminin may play a role
      in nerve guidance and 4) innervation impacts the final morphogenesis of the
      circumvallate papilla.

PMID- 12216989
TI  - Reproducing inequalities: abortion policy and practice in Thailand.
AB  - Abortion is illegal in Thailand, except in cases when it is considered necessary
      for a woman's health or in the case of rape. Yet abortions remain common and an
      important public health issue for women in Thailand. Based upon eight months'
      ethnographic research carried out in Northeast Thailand, this paper presents
      findings from a survey of 164 women of reproductive age in rural villages and
      from interviews with 19 women who have had illegal abortions. A range of
      techniques to induce abortions are used, including the consumption of
      abortifacients, massage, and uterine injections by untrained practitioners, and
      procedures carried out by trained medical personnel. This paper examines the
      effects of the current laws through the experiences of women who have undergone
      illegal abortions. Within the restrictive legal context, risk is stratified along
      economic lines. Poorer women have little choice but to resort to abortions by
      untrained practitioners. There is evidence of wide public support for the reform
      of the abortion laws to widen the circumstances under which abortion is legal. An
      ongoing movement, led by women's groups, medical and legal professionals, seeks
      to reform the law.

PMID- 12216990
TI  - Female garment factory workers in Cambodia: migration, sex work and HIV/AIDS.
AB  - Female garment factory workers in Cambodia are more exposed to HIV/AIDS than
      previously thought. Although HIV/AIDS epidemics are fast spreading in Cambodia,
      relatively little is known about the sexual health of women other than those
      perceived as commercial sex workers or married women of reproductive age. In
      depth interviews with 20 unmarried female garment factory workers, who reported
      to have engaged in multi-partnered sex through direct or discretionary commercial
      sex occupations, demonstrate that they are exposed to HIV-risk created along the
      gradients of power. Low socioeconomic status (low education, meager factory wage
      and high dependency rate at their rural households) and obligations as daughters
      to provide for the family mainly determine their entry into sex work. At the
      location of sex work, they are subjected to physical violence, alcohol and drug
      use, both self-taken and forced, and receive meager wages. In a society where
      women are expected to be virtuous and obedient to parents and husbands, these
      workers are motivated to identify male sex partners in paid sex as "sweethearts"
      rather than "guests." These factors contribute to low consistency of condom use.
      This paper demonstrates the complex interrelationships between power, cultural
      definitions of intimacy and economic dependency, which structure sexual
      relationships and the risk of HIV/AIDS.

PMID- 12216991
TI  - Negotiating care: reproductive tract infections in Vietnam.
AB  - Through case studies of two women, this paper uses a taskonomy approach to
      analyze rural Vietnamese women's narratives of prevention, treatment and
      management of vaginal discharge to illustrate care seeking, health practice and
      the pragmatism of their action. The research is based upon ethnographic research
      undertaken by the author between 1995 and 1997 in a rural district in northern
      Vietnam. This exploration illustrates the complexities of women's rationalities
      and the web of influences upon their choices-the health seeking culture as
      practiced. The women's narratives are also placed within the broader context of
      gender, power and health systems that structure their decision making. The author
      discusses how social and economic resource factors influence the choices women
      make regarding when to begin treatment for vaginal discharge and where to seek
      care. She concludes that women use their understanding of the relationships
      between health, living conditions and diseases on a day-to-day basis and that the
      practice of managing vaginal discharge is mediated by concepts of body, self and
      the body politic in Vietnam.

PMID- 12216992
TI  - Women's health in northeast Thailand: working at the interface between the local
      and the global.
AB  - An important first step in translating global statements about women's right to
      health into action programs is an assessment of the interface between local
      health culture and public health/medical practice. In this paper, we present the
      findings of an ongoing research project focusing on women's sexual and
      reproductive health in Northeast Thailand. The project is a prototype
      illustrating how formative research may be used to guide intervention development
      as well as midcourse correction. Examples are provided which clearly illustrate
      why cultural understandings of gynecological health are important to consider
      before introducing women's health programs. One case featured describes how an
      iatrogenic fear of cervical cancer has emerged from public health messages and
      screening programs. A hybrid model of cancer has evolved from preexisting local
      ideas, resulting in an exaggerated sense of risk wherein women fear that a wide
      range of common problems may potentially transform into this fatal disease. We
      argue that public health needs to be held accountable for what transpires when
      health messages are introduced into a community. Monitoring of community response
      is necessary. In the second half of the paper we describe efforts to increase
      community understanding of women's health problems, create gender and culturally
      sensitive health care services, and enhance the technical and communication
      skills of health staff.

PMID- 12216993
TI  - Gendered bodies: recruitment, management and occupational health in northern
      Thailand's electronics factories.
AB  - This paper explores workers' experiences and understandings of occupational
      health hazards in the electronics industries of northern Thailand. Women form the
      bulk of the lower-level workforce as operators responsible for assembling the
      parts that make up microchip components. Drawing data from 16 months of research
      in workers' dormitories, formal and informal interviews and questionnaire
      surveys, in this paper I explore how gender relations are central to the
      organization and experience of work in these industries. I identify "work
      process" health hazards resulting from the physical working environment, and
      "workplace" health hazards relating to the organizational and social pressures of
      the working environment. Musculoskeletal pain, eye strain, chemical exposure,
      stress, improper use of safety equipment and accidents all impact upon women
      workers' health. Additionally, risk behaviors such as amphetamine and alcohol
      use, and unprotected sex, are associated with the social context of factory work.

PMID- 12216994
TI  - Menstrual madness: women's health and well-being in urban Burma.
AB  - Women's health in peri-urban Burma is conceived of in terms of blood, strength,
      and the relationship between the body, the body politic, and the local
      environment. The regulation and volume of blood at menstruation and childbirth
      are the fundamental indicators of health and well-being. Well-being is contingent
      on harmony in and between the body and the universe. Blood flow is a key symbol
      through which women's beliefs and practices concerning their health and well
      being can be understood at the levels of pathophysiology, interpersonal
      relations, the local environment, and the wider political and moral economies of
      urban Burma.

PMID- 12216995
TI  - American Academy of Clinical Toxicology practice guidelines on the treatment of
      methanol poisoning.
AB  - EPIDEMIOLOGY: Almost all cases of acute methanol toxicity result from ingestion,
      though rarely cases of poisoning have followed inhalation or dermal absorption.
      The absorption of methanol following oral administration is rapid and peak
      methanol concentrations occur within 30-60minutes. MECHANISMS OF TOXICITY:
      Methanol has a relatively low toxicity and metabolism is responsible for the
      transformation of methanol to its toxic metabolites. Methanol is oxidized by
      alcohol dehydrogenase to formaldehyde. The oxidation of formaldehyde to formic
      acid is facilitated by formaldehyde dehydrogenase. Formic acid is converted by 10
      formyl tetrahydrofolate synthetase to carbon dioxide and water. In cases of
      methanol poisoning, formic acid accumulates and there is a direct correlation
      between the formic acid concentration and increased morbidity and mortality. The
      acidosis observed in methanol poisoning appears to be caused directly or
      indirectly by formic acid production. Formic acid has also been shown to inhibit
      cytochrome oxidase and is the prime cause of ocular toxicity, though acidosis can
      increase toxicity further by enabling greater diffusion of formic acid into
      cells. FEATURES: Methanol poisoning typically induces nausea, vomiting, abdominal
      pain, and mild central nervous system depression. There is then a latent period
      lasting approximately 12-24 hours, depending, in part, on the methanol dose
      ingested, following which an uncompensated metabolic acidosis develops and
      visualfunction becomes impaired, ranging from blurred vision and altered visual
      fields to complete blindness. MANAGEMENT: For the patient presenting with
      ophthalmologic abnormalities or significant acidosis, the acidosis should be
      corrected with intravenous sodium bicarbonate, the further generation of toxic
      metabolite should be blocked by the administration of fomepizole or ethanol and
      formic acid metabolism should be enhanced by the administration of intravenous
      folinic acid. Hemodialysis may also be required to correct severe metabolic
      abnormalities and to enhance methanol and formate elimination. For the methanol
      poisoned patient without evidence of clinical toxicity, the first priority is to
      inhibit methanol metabolism with intravenous ethanol orfomepizole. Although there
      are no clinical outcome data confirming the superiority of either of these
      antidotes over the other, there are significant disadvantages associated with
      ethanol. These include complex dosing, difficulties with maintaining therapeutic
      concentrations, the need for more comprehensive clinical and laboratory
      monitoring, and more adverse effects. Thus fomepizole is very attractive,
      however, it has a relatively high acquisition cost. CONCLUSION: The management of
      methanol poisoning includes standard supportive care, the correction of metabolic
      acidosis, the administration of folinic acid, the provision of an antidote to
      inhibit the metabolism of methanol to formate, and selective hemodialysis to
      correct severe metabolic abnormalities and to enhance methanol and formate
      elimination. Although both ethanol and fomepizole are effective, fomepizole is
      the preferred antidote for methanol poisoning.

PMID- 12216996
TI  - Introduction: children's health and the environment.

PMID- 12216997
TI  - Chronic effects of toxic environmental exposures on children's health.
AB  - Children have unusual patterns of exposure to environmental chemicals, and they
      have vulnerabilities that are quite distinct from those of adults. Increasingly,
      children's exposures to chemicals in the environment are understood to contribute
      to the causation and exacerbation of certain chronic, disabling diseases in
      children including asthma, cancer, birth defects, and neurobehavioral
      dysfunction. The protection of children against environmental toxins is a major
      challenge to modern society.

PMID- 12216998
TI  - Potential effects of certain persistent organic pollutants and endocrine
      disrupting chemicals on the health of children.
AB  - Persistent organic pollutants are lipophilic, man-made chemicals that are highly
      resistant to degradation. Due to their persistence, they have become distributed
      in small quantities throughout the world. They bioaccumulate in thefood chain and
      are stored in fatty tissues. Biomagnifications up the food chain result in
      potential widespread human exposure to these chemicals. Exposure to persistent
      organic pollutants has been associated with many adverse human health effects,
      including impaired neurodevelopment, immune and reproductive function. Many
      persistent organic pollutants also possess the ability to disrupt the normal
      functioning of the endocrine system. There is an increasing concern that low
      level exposure to these endocrine disrupting chemicals may have adverse health
      impacts, particularly during fetal, neonatal, and childhood development. Both the
      nature and severity of health outcomes may depend on the developmental time
      period during which chemical exposure occurs. This report summarizes scientific
      evidence on health effects of low-level exposure to persistent organic pollutants
      and endocrine disrupting chemicals.

PMID- 12216999
TI  - Association of prenatal exposure to an environmental contaminant with
      intellectual function in childhood.
AB  - Polychlorinated biphenyls are a family of synthetic hydrocarbon compounds that
      were used historically for a broad range of industrial purposes. Although banned
      in the 1970s, they continue to be ubiquitous in landfills, sediments, and
      wildlife. Prenatal polychlorinated biphenyl exposure was evaluated in a sample of
      children born to women who had eaten relatively large quantities of
      polychlorinated biphenyl-contaminated Lake Michigan fish. This exposure was found
      to be associated with poorer intellectual function after controlling
      statistically for a broad range of potential confounding variables. Deficits
      included poorer recognition memory in infancy, lower scores on a preschool IQ
      test, and poorer verbal IQ and reading comprehension at 11 years of age. Although
      breast-fed children were exposed postnatally to elevated levels of
      polychlorinated biphenyls from maternal milk, the adverse effects associated with
      prenatal exposure were markedly stronger in the children who were not breast-fed.
      It is not clear whether the adverse effects were attenuated in the breast-fed
      children due to certain nutrients in the breast milk or due to better quality of
      intellectual stimulation provided by the breast-feeding mothers. Virtually no
      adverse effects were found in relation to postnatal exposure to polychlorinated
      biphenyls from breast-feeding, indicating that the fetus is particularly
      vulnerable to this exposure.

PMID- 12217000
TI  - Health hazards for children at work.
AB  - The International Labor Office has estimated that there are 250 million child
      laborers (5-14 years old) worldwide, with more than 120 million of these working
      full-time. The issue is complex; child labor is an economic and social reality in
      many developing countries. Children may provide 25% or more of a family's total
      income, and many traditional cultures include child labor as an integral part of
      the child's socialization and achievement of status in the local community.
      Governments may regard child labor as a key factor in keeping their economy
      competitively viable through the provision of cheap labor for commercial
      interests. And yet child labor violates children's rights and exposes them to
      increased health risks. Children who work full-time do not attend school and
      thereby lose their inherent right to an education. They may come from families
      ravaged by poverty, live in dilapidated housing, have unsafe water supplies, poor
      sanitation, and inadequate nutritious food. Working children are vulnerable to
      anemia, fatigue, early initiation of tobacco smoking, and other health problems.
      Manual labor exposes children to injury and also to poisoning from chemicals such
      as solvents, pesticides, metals, caustic agents used on the job, to fumes and
      dust, and other toxic, work-related byproducts. The International Labor
      Organization has sought to control the most abusive of child labor practices
      throughout the world. Solutions to this complex and intractable worldwide problem
      will also require infrastructure changes in the economic and social incentives to
      child labor, enlightened public health policies, and community-level advocacy and
      involvement.

PMID- 12217001
TI  - Poisons in the air: a cause of chronic disease in children.
AB  - Children represent the largest subpopulation of those susceptible to the adverse
      effects of air pollution. Compared to adults, children express a greater
      vulnerability, which can be explained by differences in: the circumstances of
      exposure related to age, their activities, their child status, differences in
      lung anatomy and physiology, differences in the clinical expression of disease,
      and their organ maturity. Many factors have to be assessed in order to evaluate
      the severity of toxic exposures: pollutant solubility, particle size,
      concentration, reactivity of pollutants, and pattern of ventilation. Within the
      numerous air pollutants, some are of special concern for children. For example,
      ozone has been shown to affect the lungs of healthy school children, especially
      asthmatics. Airborne particles, nitrogen oxides, sulfur oxides, and acid aerosols
      have also been shown to induce acute respiratory symptoms, asthma, and
      bronchitis. Of particular importance is carbon monoxide, which, under certain
      circumstances, may be found in highly toxic concentrations indoors where children
      spend most of their time. Special attention has to be given to children's unique
      differences in order to evaluate the clinical consequences of their toxic
      exposures. This circumstance emphasizes the key roles of poison centers, clinical
      toxicologists, and pediatricians, all of whom can collaborate on the
      identification, assessment, and surveillance of toxic risk for child health and
      development.

PMID- 12217002
TI  - The sentinel role of poisons centers in the protection of children's
      environmental health.
AB  - Growing concern exists about the threats posed by environmental pollutants and
      physical agents on children's health. A number offactors, including
      globalization, increased industrialization, and trade of chemicals and poverty
      have an impact on the quality of the environment and on children's health. Acute
      toxic exposures lead to poisoning, and chronic low-level exposures may cause
      functional and organ damage during periods of special vulnerability. The need to
      protect children's environmental health is urgent, in view of the magnitude of
      the problem and the fact that "children are not little adults." The effects
      suffered during special developmental periods-"windows of vulnerability"-can be
      permanent and irreversible. The main global environmental problems affecting
      children's health are lack of access to safe drinking water and sanitation and
      exposure to indoor air pollution. Furthermore, environmentally related accidents,
      injuries, and poisonings have a major impact on children and adolescent's
      morbidity and mortality. A number of examples that illustrate the complexity of
      assessing and dealing with children's environmental health issues are presented.
      A Task Force on the Protection of Children's Environmental Health that aims to
      prevent disease and disability in children associated with chemical and physical
      threats was set up in 1999 by the World Health Organization. The priorities for
      action include the consideration of accidents, injuries, and poisonings
      (accidental, intentional, and occupational), and children in the workplace (e.g.,
      scavenging children, children in cottage industries). Poisons Centers and related
      toxicology centers are in a strategic position to play a "sentinel" role in the
      protection of children's environmental health. They record acute and chronic
      toxic exposures in children in a harmonized manner, using controlled vocabularies
      and definitions. This will allow collecting a large, highly valuable database on
      the main toxicological problems affecting children, including those of
      environmental origin. The analysis of observations entered in such a database
      will help assess the burden of disease and collect the evidence for planning
      prevention and promoting regulatory measures. Centers are called to play a
      proactive role in raising awareness about children's environmental health and
      contribute to research, information dissemination, training, and other activities
      required for the protection of children's health and development.

PMID- 12217003
TI  - Methanol poisoning exposures in the United States: 1993-1998.
AB  - OBJECTIVES: We investigated U.S. methanol-poisoning exposures since little recent
      information is available about the frequency, sources of methanol, or outcomes of
      individuals who consume methanol. METHODS: We reviewed human methanol exposures
      reported to the American Association of Poison Control Centers Toxic Exposure
      Surveillance System 1993-1998. RESULTS: The mean number of cases per year was
      2254. Each year 167 cases had an outcome of moderate effect, major effect, or
      death. One death occurred in every 183 exposures to methanol. Symptomatic cases
      increased abruptly from 1.8 to 2.5% for infants and children, from 14.1 to 12.3%
      for adolescents and adults, while the intentional exposures increased from < 1 to
      21% for adolescents, and 11% for adults. Cases occurred in every decade of life
      but toddlers had the highest number of exposures. In 68 methanol fatalities,
      confusion developedfollowed by coma, hypotension, respiratory depression, and
      cerebral edema. Blood methanol levels were above 100mg/dL (70%), metabolic
      acidoses (62%), and anion gaps > 25 (100%). Methanol products were recorded,
      showing windshield wiper fluids to be 60.8% of exposures. Other automotive
      sources were 23.7%. Commercial nonautomotive products were 12.2% and pure
      methanol products were 2.3%. Unintentional exposures were reported in 90.3% of
      all cases, while 8.3% were due to intentional exposures, and 1.4% wasfor unknown
      or mixed reasons. Intentional exposures resulted from suspected suicides (51.2%)
      and from abuse and misuse (38.8%). CONCLUSIONS: Methanol poisonings continue to
      occur in the United States with toddlers at the highest risk for exposure, but
      adolescents and adults at the highest risk for life-threatening intoxications.
      Over half of product-identified cases were due to consumption of windshield
      wiperfluid. Efforts should be undertaken to minimize methanol exposures.

PMID- 12217004
TI  - Efficacy of charcoal hemoperfusion in massive carbamazepine poisoning.
AB  - BACKGROUND: Carbamazepine poisoning can be life threatening. The role and
      efficacy of extracorporeal drug clearance is not clearly defined. CASE REPORT: A
      16-year-old male ingested 34g of slow-release carbamazepine. His course was
      complicated by seizures, recurrent cardiac arrests, and renalfailure. Intestinal
      ileus at the time of presentation prevented effective gastrointestinal
      decontamination. His carbamazepine concentration peaked at 93.8 mg/L
      (397micromol/L) 106 hours after ingestion. There was evidence suggesting ongoing
      absorption for 120 hours. He underwent seven episodes of charcoal hemoperfusion
      for a total of 109.25 hours. He subsequently made a full recovery. METHODS: The
      efficacy of charcoal hemoperfusion was evaluated by measuring the carbamazepine
      concentrations in the afferent and efferent loops of the hemoperfusion cartridge
      using 17 paired convenience samples. Extraction ratios were calculated and
      plotted against timefor each individual episode of charcoal hemoperfusion.
      CONCLUSION: The extraction ratio was linearly related to time, and ranged 0.46
      0.02. The peak clearance was 69 mL/min. Cartridge saturation was defined as a
      clearance that was equal to an estimate of the patient's intrinsic clearance. In
      our patient, this was equivalent to an extraction ratio of 0.2 at a flow rate of
      150 mL/min. By this definition, cartridge saturation appeared to occur at 7
      hours. Charcoal hemoperfusion was associated with a significant reduction in the
      apparent half-life, which is most easily explained by clearance from the central
      vascular compartment, during a prolonged absorptive phase. The patient made full
      recovery without evidence of neurological deficit.

PMID- 12217005
TI  - Acute propylene glycol ingestion.
AB  - BACKGROUND: We describe a case of acute propylene glycol toxicity following
      ingestion of ethanol and propylene glycol-containing antifreeze in which blood
      lactate, serum propylene glycol, ethanol, and CO2 concentrations were serially
      measured. CASE REPORT: A 61-year-old man was hospitalized after acute ingestion
      of ethanol and automotive antifreeze. His clinical presentation and course were
      essentially unremarkable. Initial lab tests revealed serum ethanol concentration,
      167 mg/dL, normal serum electrolytes and osmol gap, 120 mOsm/kg. Intravenous 10%
      ethanol infusion was begun for suspected ethylene glycol toxicity and
      discontinued at approximately 17 hours post-ingestion. Toxicological analysis of
      urine was positive for ethanol and propylene glycol, and negative for ethylene
      glycol, methanol, and isopropanol. Blood lactate was mildly elevated and serum
      CO2 concentration was normal. Gas chromatographic analysis of serial serum
      specimens for propylene glycol concentration revealed a maximum value of 470
      mg/dL at 7 hours and a nonlinear decline to below detection limit (3 mg/dL) at 57
      hours after antifreeze ingestion. The patient was discharged on hospital day 2.
      CONCLUSION: The propylene glycol elimination pattern, absence of significant acid
      base disturbance, and minimal lactate elevation in this case are consistent with
      ethanol-related inhibition of propylene glycol metabolism. The effect of ethanol
      on clinical outcome after acute propylene glycol intoxication remains uncertain.

PMID- 12217006
TI  - Acute respiratory arrest following hemlock (Conium maculatum) intoxication.

PMID- 12217008
TI  - Pitfalls of correlation of childhood blood lead and cognitive development.

PMID- 12217007
TI  - Childhood blood lead and cognition.

PMID- 12217009
TI  - Chronic and criminal administration of Nerium oleander.

PMID- 12217010
TI  - Retrospective evaluation of cetirizine (zyrtec) ingestion.

PMID- 12217012
TI  - Comprehensive survey of combinatorial library synthesis: 2001.

PMID- 12217011
TI  - Arsenic exposure and health effects.

PMID- 12217013
TI  - New scaffolds for combinatorial synthesis. 1. 5-sulfamoylisatins and their
      reactions with 1,2-diamines.
AB  - 3,3-Dichloro-5-(4-methylpiperidinosulfonyl)-2-indolinone (3) and 5
      sulfamoylisatins 4 have been synthesized from 5-chlorosulfonyl-3,3-dichloro-2
      indolinone (1). Compounds 4 are promising scaffolds for the solid- and liquid
      phase syntheses of new combinatorial libraries of various heterocycles. Thus, the
      reactions of 4 with 1,2-diamines, such as o-phenylenediamine (5) and
      aminoguanidine hydrochloride (6), 1,2-diaminoimidazoles (9), and
      thiosemicarbazide led, respectively, to new heterocycles 7 and 8 and new
      combinatorial libraries of triazinoindoles 10 and 15. Chemsets 4, 10, and 15 were
      isolated as crystalline solids that were purified by recrystallization from a
      suitable solvent and characterized by spectroscopic methods.

PMID- 12217014
TI  - Efficient solid-phase synthesis of sulfahydantoins.
AB  - A novel solid-phase strategy allows the efficient preparation of "traceless"
      sulfahydantoins. A total of 28 derivatives, with crude purity generally higher
      than 85%, were prepared by parallel synthesis. Through reductive alkylations,
      Mitsunobu reactions, and sulfamoylation reactions on oxime resin, the synthetic
      strategy affords sulfahydantoin derivatives selectively substituted at N(2), N(5)
      and N(2), N(5) positions, although yields of disubstituted compounds are lower.
      The mild reaction conditions involved lead to sulfahydantoins without
      racemization.

PMID- 12217016
TI  - Standardization protocols and optimized precursor sets for the efficient
      application of automated parallel synthesis to lead optimization: a Mitsunobu
      example.
AB  - A strategy has been developed for the efficient application of automated parallel
      synthesis to specific aspects of the lead optimization processes employed in drug
      discovery. The method involves the synthesis of collections of compounds using
      sets of precursors designed to encompass established medicinal chemistry
      principles and that have been concurrently optimized with respect to a specific
      chemical transformation. The strategy is illustrated using an automated Mitsunobu
      protocol employing sets of aliphatic alcohols and phenols as precursors. The
      former has been formatted to perform simple alkyl homologation exercises, with
      the latter being designed for use in diversity-based studies.

PMID- 12217015
TI  - Application of microgels as polymer supports for organic synthesis: preparation
      of a small phthalide library, a scavenger, and a borohydride reagent.
AB  - Microgel polymers containing a series of functional groups have been prepared.
      These microgels were composed of cross-linked poly(styrene) and were prepared by
      radical polymerization in solution. The microgel polymers exhibit good solubility
      in an array of different organic solvents, and in addition, they can be
      efficiently precipitated by the addition of methanol and isolated by filtration.
      A nine-member phthalide library was synthesized using an aminomethyl
      functionalized microgel 5. To further demonstrate the versatility of these
      microgel polymers, tris(2-aminoethyl)amino microgel 11 was examined as a
      scavenger reagent to remove unreacted isocyanate after a urea synthesis. Finally,
      a microgel-supported ammonium borohydride reagent 14 was successfully prepared
      and used as a reducing agent. Notable features of these microgels are that in all
      applications the progress of the reaction could be monitored by standard NMR
      techniques and their preparation is performed using common glassware and
      techniques found in all organic laboratories.

PMID- 12217017
TI  - Design and synthesis of a 256-membered pi-conjugated oligomer library of
      regioregular head-to-tail coupled quater(3-arylthiophene)s.
AB  - The rapid solid-phase synthesis of pi-conjugated oligomers is demonstrated by
      utilizing the parallel and the "mix-and-split" methods for the preparation of a
      library of 256 regioregular head-to-tail coupled oligo(3-arylthiophene)s.
      Chemical diversity was introduced to the growing oligomer starting from four
      resin-bound 3-(p-X-phenyl)-2-silylthiophenes via an iterative sequence of
      iodinations and Suzuki cross-coupling reactions with four 3-(p-X-phenyl)thiophene
      boronic esters (X = CF(3), H, CH(3), OCH(3)). Liberation from the solid support
      with TFA and subsequent chromatographic purification by normal-phase LC-MS
      provided all 256 regioregular head-to-tail coupled quater(3-arylthiophene)s.

PMID- 12217018
TI  - Preparation and improved stability of N-Boc-alpha-amino-5-acyl Meldrum's acids, a
      versatile class of building blocks for combinatorial chemistry.
AB  - The preparation of novel N-Boc-alpha-amino-5-acyl Meldrum's acids is described.
      The synthetic inaccessibility and instability of several of these products have
      led to the development of a protocol that allows the synthesis of their
      corresponding 4-(dimethylamino)pyridine (DMAP) salts (5-AMA-DMAP's), which
      exhibit superior stability compared to that of the free 5-AMA. A simple and
      expedient ion-exchange method was developed for the quantitative removal of DMAP
      to liberate the synthetically useful DMAP-free form when needed.

PMID- 12217019
TI  - New efficient route for solid-phase synthesis of benzimidazole derivatives.
AB  - A simple and efficient method for the solid-phase synthesis of benzimidazole
      libraries is described. Monoalkylation of various o-phenylenediamines on resin
      bound bromoacetamide proceeded smoothly to give the monoalkyl resin-bound o
      phenylenediamines in high yields. Subsequent cyclization of the diamines with
      various aldehydes afforded solid-supported benzimidazoles. Cleavage from the
      resin gave benzimidazoles in good yields. The present method enabled the
      introduction of the diversity on the benzene ring of imidazoles.
      Azabenzimidazoles, such as 4-azabenzimidazoles, 5-azabenzimidazoles, and purines,
      were also synthesized in good yields with high purities by the same procedure.

PMID- 12217020
TI  - Efficient solid-phase synthesis of 1,3,5-trisubstituted 1,3,5-triazine-2,4,6
      triones.
AB  - The solid-phase synthesis of 1,3-disubstituted and 1,3,5-trisubstituted 1,3,5
      triazine-2,4,6-triones from MBHA and Wang resin is described. Reaction of resin
      bound amino acids with isocyanates yield resin-bound ureas, which further react
      with chlorocarbonyl isocyanate in toluene at 65 degrees C to selectively afford
      the resin-bound 1,3-disubstituted 1,3,5-triazine-2,4,6-triones. Selective
      alkylation at the N-5 position of the resin-bound 1,3-disubstituted 1,3,5
      triazine-2,4,6-triones was accomplished by treatment with alkyl halides in the
      presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The desired products were
      cleaved from their solid support and obtained in good yield and purity. The
      method can be employed in production of toltrazuril analogue libraries for
      identification of new anticoccidial agents.

PMID- 12217021
TI  - Solid-phase syntheses of 1,2,4-trisubstituted urazole and thiourazole
      derivatives.
AB  - Solid-phase syntheses of 1,2,4-trisubstituted urazole and thiourazole derivatives
      have been accomplished. The synthesis began with the coupling of
      carbonylimidazole-Wang resin with a disubstituted hydrazine. The resultant
      carbazate was coupled with an isocyanate or isothiocyanate. Subsequent heating of
      the resin in the presence of triethylamine or potassium t-butoxide induced
      cyclization and released the desired (thio)urazole into solution. Most of the
      products were obtained in high yields and purities. Structural diversity can be
      further expanded at the R(2) substituent by performing the palladium-mediated
      Suzuki coupling reaction.

PMID- 12217022
TI  - Use of Vilsmeier reagent for the solid-phase synthesis of 1,5-disubstituted 4,5
      dihydro-1H-imidazoles and disubstituted 4,5-dihydro-1H-imidazolylbenzimidazoles.
AB  - The solid-phase synthesis of novel imidazolines and
      dihydroimidazolylbenzimidazoles is described. Resin-bound diamines, derived from
      resin-bound N-acylated amino acid amides, were cyclized using Vilsmeier reagent
      to yield imidazolines following cleavage. Similarly, cyclization of resin-bound
      tetraamines having two secondary amines and an o-dianiline yielded
      dihydroimidazolylbenzimidazoles following cleavage.

PMID- 12217023
TI  - Traceless solid-phase synthesis of bicyclic dihydropyrimidones using
      multidirectional cyclization cleavage.
AB  - Solid-phase and solution-phase protocols for the synthesis of furo[3,4
      d]pyrimidines, pyrrolo[3,4-d]pyrimidines, and pyrimido[4,5-d]pyridazines are
      reported. The multistep solid-phase sequence involves the initial high-speed,
      microwave-promoted acetoacetylation of hydroxymethylpolystyrene resin with methyl
      4-chloroacetoacetate. The immobilized 4-chloroacetoacetate precursor was
      subsequently subjected to three-component Biginelli-type condensations employing
      urea and a variety of aromatic aldehydes. The resulting 6-chloromethyl
      functionalized resin-bound dihydropyrimidones served as common chemical platforms
      for the generation of the desired heterobicyclic scaffolds using three different
      traceless cyclative cleavage strategies. The corresponding furo[3,4-d]pyrimidines
      were obtained by microwave flash heating in a rapid, thermally triggered,
      cyclative release. Treatment of the chloromethyl dihydropyrimidone intermediates
      with a variety of primary amines followed by high-temperature microwave heating
      furnished the anticipated pyrrolo[3,4-d]pyrimidine scaffolds via nucleophilic
      cyclative cleavage. In a similar way, reaction with monosubstituted hydrazines
      resulted in the formation of pyrimido[4,5-d]pyridazines. All compounds were
      obtained in moderate to good overall yields and purities.

PMID- 12217024
TI  - Design strategies for multielectrode arrays applicable for high-throughput
      impedance spectroscopy on novel gas sensor materials.
AB  - This paper reports the first design and fabrication of a 64 multielectrode array
      for high-throughput impedance spectroscopy. The purpose of this work is the
      development of a measurement system for the discovery and improvement of sensor
      materials using combinatorial methods. An array of interdigital capacitors (IDC)
      screen-printed onto a high-temperature-resistant Al(2)O(3) substrate is
      determined to be the optimal test plate. The electrode layout, and therefore also
      the idle capacity, is determined by specific requirements. Calculation of the
      idle capacity of the IDC as a function of the electrode width and distance allows
      adjustment and thus optimization of the array. Parasitic effects caused by the
      leads and contacts are compensated by a software-aided calibration. Apart from
      the use of the substrates for discovery of new sensor materials, the presented
      electrode array is also suitable for electrocatalytic applications as well as
      impedance spectroscopic studies of semiconductors and dielectrics.

PMID- 12217025
TI  - Combinatorial synthetic design. Solution and polymer-supported synthesis of
      heterocycles via intramolecular aza Diels-Alder and imino alcohol cyclizations.
AB  - A flexible synthetic strategy for combinatorial chemical applications has been
      developed on the basis of an aldehyde-bridge-alkene motif as the key component in
      several intramolecular cycloaddition reactions. This strategy was explored most
      extensively with the formal aza Diels-Alder cyclization, which affords a series
      of configurationally and functionally diverse heterocyclic compounds. The
      substrates included substituted salicylaldehydes, glyoxylic esters and amides,
      and N-acyl-alpha-aminoaldehydes; all reacted with a variety of anilines to yield
      different tetrahydroquinoline products. The cyclization of the aminoaldehydes was
      also translated from solution and optimized for solid phase. The stepwise
      mechanism of this cycloaddition suggested that the cationic intermediate from
      initial ring closure could be trapped by a variety of nucleophiles. This
      suggestion was confirmed by cyclization of amino alcohols and related compounds.

PMID- 12217026
TI  - SPOCC-194, a new high functional group density PEG-based resin for solid-phase
      organic synthesis.
AB  - A novel polymer matrix for solid-phase synthesis, SPOCC(194) resin (1), was
      designed featuring a backbone of homogeneous tetraethylene glycol (TEG(194))
      macromonomer linked by quaternary carbon junctions and terminating in primary
      alcohol functionality. Beaded SPOCC(194) resin was effectively prepared by
      suspension polymerization of oxetanylated TEG macromonomer 5 in stirred silicon
      oil. Mechanically stable and inert to a diverse range of reaction conditions,
      SPOCC(194) possessed a high hydroxyl group loading (0.9-1.2 mmol/g) for substrate
      attachment and swelled effectively ( approximately 2-4 mL/g) in a variety of
      organic and aqueous solvents. Developed for solid-phase synthesis at high
      reactant concentrations for driving organic and aqueous reactions to completion,
      SPOCC(194) exhibited high functional group density (mmol/mL) similar to that of
      low-loaded aminomethylated polystyrene-divinylbenzene copolymer (PS-1%DVB) yet
      significantly higher than that of PEGA(1900), SPOCC(1500), and TentaGel S. High
      resolution MAS NMR spectra of Fmoc-derivatized SPOCC(194) indicate that
      monitoring of functional group transformation is possible. Moreover, by
      employment of a nonaromatic resin-linker combination, electrophilic chemistry,
      such as Lewis acid catalyzed glycosylation and Friedel-Crafts acylation, was
      selectively performed on substrate bound to SPOCC(194) resin. Such properties
      make SPOCC(194) resin a promising new polymer matrix for the support-bound
      construction of small organic molecules by parallel and combinatorial synthesis
      and the scavenging of solution-phase reactants or byproducts.

PMID- 12217027
TI  - Preparation of N-alkylated pyridones via selective N-alkylation of 2
      alkoxypyridines on solid phase.
AB  - Regioselective solid-phase synthesis of N-alkylated 2-pyridones has been carried
      out starting from 2-halopyridines. Variously substituted 2-halopyridines were
      linked to a Wang resin in quantitative yields to afford 2-alkoxypyridines. The
      coupled products were then reacted with a variety of alkyl halides, resulting in
      tandem alkylation and cleavage from the resin to generate N-alkylated pyridones
      with no detectable traces of O-alkylated products. The scope and limitations of
      this exceptionally selective reaction have been studied.

PMID- 12217028
TI  - Solid-phase synthesis of alkyl aryl ethers via the Ullmann condensation.
AB  - Alkyl aryl ether formation is a frequently employed reaction in organic
      synthesis. Ullmann condensation is an alternative method to the widely used
      Mitsunobu reaction and is very useful in situations where application of the
      Mitsunobu reaction is limited. By application of this reaction to solid-phase
      synthesis of a series of alkyl aryl ethers, reaction conditions (catalyst,
      solvent, temperature, time, etc.) for a sterically hindered class of alcohols
      were investigated and optimized. A range of aryl halides was used to explore the
      scope of the reaction in solid phase.

PMID- 12217030
TI  - Preparation of poly(L-lactide)-based microspheres having a cationic or anionic
      surface using biodegradable surfactants.
AB  - Poly(L-lactide)-based microspheres having cationic or anionic surfaces were
      prepared using polydepsipeptide-block-poly(L-lactide)s as surfactants.
      Polydepsipeptide-block-poly(L-lactide)s having amino or carboxylic acid groups on
      their side chains were synthesized through anionic ring-opening polymerizations
      of L-lactide using the corresponding protected polydepsipeptides as
      macroinitiators and consequent deprotections. Since these amphiphilic copolymers
      consisting of hydrophobic segments and hydrophilic segments with amino or
      carboxylic acid groups could be converted to cationic or anionic block
      copolymers, they could act as surfactants preparing poly(L-lactide)-based
      microspheres by an oil-in-water emulsion method. The amount of ionic groups
      located on the surfaces of the obtained microspheres was found to increase with
      increasing the feed of charged polydepsipeptide-block-poly(L-lactide)s in the
      blend of poly(L-lactide) and block copolymers. The average diameters of the dried
      microspheres estimated by scanning electron microscopy were found to decrease
      with an increase in feed of block copolymers in polymer blends.

PMID- 12217031
TI  - Monitoring the enzymatic polymerization of 4-phenylphenol by matrix-assisted
      laser desorption ionization time-of-flight mass spectrometry: a novel approach.
AB  - Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass
      spectrometry is a powerful tool for polymer characterization. It has been used to
      understand the enzymatic polymerization of 4-phenylphenol and to monitor number
      average molecular weight and weight average molecular weight of the polymer as a
      function of systematic addition of hydrogen peroxide (H(2)O(2)) in the reaction.
      A novel method, an introduction of internal standard for quantification of data,
      has been developed for MALDI-TOF MS to investigate the fate of each mers during
      the reaction. The preliminary data suggest that this approach provides new
      insight on the enzymatic synthesis, which is not available by other techniques.
      For the first time, we are able to understand the fate of several mers as a
      function of reaction conditions. The relative content of each mer increases with
      the addition of H(2)O(2), except for dimer and trimer. For example, the
      concentration of dimer species decreases as a function of H(2)O(2). On the other
      hand, the concentration of trimer species increases first and then decreases in
      the course of the reaction.

PMID- 12217032
TI  - Enzymatic hydrolysis of chemosynthesized atactic poly(3-hydroxybutyrate) by
      poly(3-hydroxyalkanoate) depolymerase from Acidovorax Sp. TP4 and Ralstonia
      pickettii T1.
AB  - The enzymatic degradability of chemosynthesized atactic poly([R,S]-3
      hydroxybutyrate) [a-P(3HB)] by two types of extracellular poly(3
      hydroxyalkanoate) (PHA) depolymerases purified from Ralstonia pickettii T1
      (PhaZ(ral)) and Acidovorax Sp. TP4 (PhaZ(aci)), defined respectively as PHA
      depolymerase types I and II according to the position of the lipase box in the
      catalytic domain, were studied. The enzymatic degradation of a-P(3HB) by
      PhaZ(aci) depolymerase was confirmed from the results of weight loss and the
      scanning electron micrographs. The degradation products were characterized by one
      and two-dimension (1)H NMR spectroscopy. It was found that a-P(3HB) could be
      degraded into monomer, dimer, and trimer by PhaZ(aci) depolymerase at
      temperatures ranging from 4 to 20 degrees C, while a-P(3HB) could hardly be
      hydrolyzed by PhaZ(ral) depolymerase in the same temperature range. These results
      suggested that the chemosynthesized a-P(3HB) could be degraded in the pure state
      by natural PHA depolymerase.

PMID- 12217033
TI  - Mercury intrusion porosimetry, nitrogen adsorption, and scanning electron
      microscopy analysis of pores in skin.
AB  - Stability of collagenous matrixes such as skin and leather with respect to
      changes in their dimensions on heating has long been correlated with degree and
      type of cross links formed and short-range ordering in angstrom unit scales.
      Macroscopic dimensional changes may be expected to involve alterations in the
      long-range order as well as supramolecular assemblies in skin and leather. This
      study relates thermal shrinkage of skin matrixes with alterations observed in
      micro-, meso-, and macroporic structures. Changes in the pore structure of skin
      associated with thermal shrinkage have been studied using nitrogen adsorption and
      mercury intrusion porosimetry measurements. A comparison of results obtained
      using both techniques has been made. These results indicate that although the
      percentage porosity of the matrix decreases, the BET specific surface area
      increases on shrinkage. An insight into the changes in the pore systems of skin
      induced by thermal shrinkage has been gained.

PMID- 12217034
TI  - Intracellular signal-responsive artificial gene regulation for novel gene
      delivery.
AB  - We describe two types of artificial gene-regulation systems responding to cyclic
      AMP-dependent protein kinase (PKA) or caspase-3. These molecular systems use
      newly synthesized cationic polymers, PAK and PAC. The PAK polymer includes
      substrate oligopeptide for PKA, ARRASLG, as receptor of PKA signal, while the PAC
      polymer possesses oligopeptide that is comprised of a substrate sequence of
      caspase-3, DEVD, and a cationic oligolysine, KKKKKK. These polymers formed stable
      complexes with DNA to totally suppress the gene expression. However, PKA or
      caspase-3 signal disintegrates the PAK-DNA or the PAC-DNA complex, respectively.
      This liberates the DNA and activated the gene expression. These systems are the
      first concept of an intracellular signal-responsive gene-regulation system using
      artificial polymer. We expect that these systems can be applied to the novel
      highly cell specific gene delivery strategy that is involved in our previously
      proposed new drug delivery concept, the drug delivery system based on responses
      to cellular signals.

PMID- 12217035
TI  - Characterization of a genetically engineered elastin-like polypeptide for
      cartilaginous tissue repair.
AB  - Elastin-like polypeptides (ELPs) are artificial polypeptides with unique
      properties that make them attractive as a biomaterial for tissue-engineered
      cartilage repair. ELPs are composed of a pentapeptide repeat, Val-Pro-Gly-Xaa-Gly
      (Xaa is any amino acid except Pro), that undergo an inverse temperature phase
      transition. They are soluble in aqueous solution below their transition
      temperature (T(t)) but aggregate when the solution temperature is raised above
      their T(t). This study investigates the rheological behavior of an un-cross
      linked ELP, below and above its T(t), and also examines the ability of ELP to
      promote chondrogenesis in vitro. A thermally responsive ELP with a T(t) of 35
      degrees C was synthesized using recombinant DNA techniques. The complex shear
      modulus of the ELP increased by 3 orders of magnitude as it underwent its inverse
      temperature phase transition, forming a coacervate, or gel-like, ELP phase.
      Values for the complex shear moduli of the un-cross-linked ELP coacervate are
      comparable to those reported previously for collagen, hyaluronan, and cross
      linked synthetic hydrogels. Cell culture studies show that chondrocytes cultured
      in ELP coacervate maintain a rounded morphology and their chondrocytic phenotype,
      characterized by the synthesis of a significant amount of extracellular matrix
      composed of sulfated glycosaminoglycans and collagen. These results suggest that
      ELPs demonstrate great potential for use as in situ forming scaffolds for
      cartilaginous tissue repair.

PMID- 12217036
TI  - Interchain heterogeneity of enzymatically deesterified lime pectins.
AB  - Two series of pectins with different levels and patterns of methyl esterification
      were produced by treatment of a very highly methylated lime pectin with a fungus-
      or plant-pectin methylesterase. The interchain distribution of free carboxyl
      groups was investigated by size exclusion and ion exchange chromatography.
      "Homogeneous" populations with respect to molar mass or charge density were
      thereby obtained, and their composition, molar mass, and calcium binding
      properties were investigated. The composition varies from one size exclusion
      chromatography fraction to another, the highest molar mass fraction being richer
      in rhamnogalacturonic sequences and exhibiting a slightly higher degree of
      methylation (DM). Separation of pectins by ion exchange chromatography revealed a
      narrow charge density distribution for pectins deesterified by fungus-pectin
      methylesterase, in agreement with a multichain mechanism. Conversely, pectins
      deesterified by plant-pectin methylesterase exhibited a very large charge density
      distribution suggesting a processive mechanism. The interchain polydispersity
      with regard to DM was however shown to have no impact on calcium binding
      properties of the different fractions. The progressive dimerization through
      calcium ions with decreasing DM of pectins deesterified by plant-pectin
      methylesterase seems to be the result of a peculiar intrachain pattern of methyl
      esterification that can be attributed to a multiple attack mechanism.

PMID- 12217037
TI  - Star-shaped poly(ethylene glycol)-block-polyethylenimine copolymers enhance DNA
      condensation of low molecular weight polyethylenimines.
AB  - Star-shaped poly(ethylene glycol)-block-polyethylenimine [star-(PEG-b-PEI)]
      significantly enhance plasmid DNA condensation of low molecular weight (MW) PEIs.
      The star-block copolymers were prepared via a facile synthesis route using
      hexamethylene diisocyanate as linker between PEG and PEI blocks. NMR and FT-IR
      spectroscopy confirmed the structures of intermediately activated PEG and final
      products. Furthermore, the copolymers were characterized by size exclusion
      chromatography, static light scattering, and viscosimetry. Their molecular
      weights (M(w) 19-26 kDa) were similar to high MW PEI (25 kDa). Thermoanalytical
      investigations (thermogravimetric analysis, differential scanning calorimetry)
      were also performed and verified successful copolymer synthesis. DNA condensation
      with the low MW PEIs (800 and 2000 Da) and their 4- and 8-star-block copolymers
      was studied using atomic force microscopy, dynamic light scattering, zeta
      potential measurements, and ethidium bromide (EtBr) exclusion assay. It was found
      that low MW PEIs formed huge aggregates (500 nm to 2 microm) in which DNA is only
      loosely condensed. By contrast, the star-block copolymers yielded small (80-110
      nm), spherical and compact complexes that were stable against aggregation even at
      high ionic strength and charge neutrality. Furthermore, as revealed in the EtBr
      exclusion assay these star-block copolymers exhibited a DNA condensation
      potential as high as high MW PEI. Since these star-(PEG-block-PEI) copolymers are
      composed of relatively nontoxic low MW PEI and biocompatible PEG, their potential
      as gene delivery agents merits further investigations.

PMID- 12217038
TI  - Biomimetic synthesis of a water soluble conducting molecular complex of
      polyaniline and lignosulfonate.
AB  - A new biomimetic route for the synthesis of a conducting molecular complex of
      polyaniline (Pani) and a natural polyelectrolyte, lignosulfonate (LGS) is
      presented. A poly(ethylene glycol) modified hematin (PEG-hematin) was used to
      catalyze the polymerization of aniline in the presence of LGS to form a Pani/LGS
      complex. UV-vis, FTIR, conductivity and TGA studies for the LGS-polyaniline
      complex indicate the presence of a thermally stable and electrically conductive
      form of polyaniline. Also the presence of LGS in this complex, an inexpensive
      byproduct from pulp processing, provides a unique combination of properties such
      as electronic conductivity, processability and biodegradability. The use of this
      conductive complex for corrosion protection is also proposed.

PMID- 12217039
TI  - Preparation of vinylated polysaccharides and photofabrication of tubular
      scaffolds as potential use in tissue engineering.
AB  - Polysaccharides, such as heparin, hyaluronan, and chitosan, were partially
      derivatized with a styryl or a methacryloyl group by condensation at a carboxyl
      or an amino group of the polysaccharides with 4-vinylaniline or 4-vinylbenzoic
      acid. The degree of substitution depended on the reaction conditions. These
      compounds with low degrees of derivatization produced water-swollen hydrogels
      only at relatively high concentrations (30-40 wt %) in the presence of a
      carboxylated camphorquinone upon visible light irradiation. A high degree of
      derivatization of heparin increased the gel yield and concomitantly reduced the
      degree of swelling. The copolymerization of these vinylated polysaccharides with
      styrenated gelatin considerably reduced the degree of swelling. Tubular
      photoconstructs were prepared by photocopolymerization of vinylated
      polysaccharide and vinylated gelatin. The mixing of diacrylated poly(ethylene
      glycol) with vinylated polysaccharide improved the burst strength of photogels
      against the gradual infusion of water. These photocurable polysaccharides may be
      used as photocured scaffolds in tissue-engineered devices.

PMID- 12217040
TI  - Synthesis and properties of degradable poly(urethane urea)s to be used for
      ligament reconstructions.
AB  - In the present study we describe the synthesis, wet spinning, mechanical testing,
      and degradation of poly(urethane urea)s (PUURs) intended for clinical use in
      anterior cruciate ligament (ACL) reconstruction. The effects of soft segment
      chemical composition and molar mass and the kind of diamine chain extender on the
      material properties were investigated. It was found that the fibers made of PUUR
      with polycaprolactone diol (PCL530) as soft segment and MDI/1,3-DAP as hard
      segment (PCL530-3) have high tensile strength and high modulus and when degraded
      keep their tensile strength for the time demanded for the application. In
      conclusion, from a chemical and mechanical point of view PUUR fibers of PCL530-3,
      ARTELON, are suitable for designing a degradable ACL device.

PMID- 12217041
TI  - A novel method for the determination of carbonyl groups in cellulosics by
      fluorescence labeling. 1. Method development.
AB  - A novel method to accurately determine the carbonyl content in cellulosic
      materials by fluorescence labeling with carbazole-9-carboxylic acid [2-(2
      aminooxyethoxy)ethoxy]amide has been developed. The procedure can readily be
      incorporated into a gel permeation chromatography (GPC) system with refractive
      index and multiple-angle laser light scattering detection. Both a homogeneous
      procedure, working in DMAc/LiCl (2.5%, w/v), and a heterogeneous derivatization
      approach, using aqueous buffer pH 4.0, for determination of carbonyls in pulps
      have been optimized with regard to reaction conditions, presence of catalysts,
      reproducibility, and completeness of conversion. The homogeneous labeling
      requires prolonged reaction times and removal of excess marker prior to GPC
      analysis by a time-consuming precipitation-washing-redissolution sequence, which
      is not needed in the heterogeneous approach. The heterogeneous procedure offers
      the additional advantages of higher efficiency, shortened analysis times,
      increased simplicity, and widest applicability.

PMID- 12217042
TI  - A novel method for the determination of carbonyl groups in cellulosics by
      fluorescence labeling. 2. Validation and applications.
AB  - Fluorescence labeling with the marker carbazole-9-carboxylic acid [2-(2
      aminooxyethoxy)ethoxy]amide was shown to be a promising approach toward the
      accurate determination of carbonyls in cellulosic materials. Combined with gel
      permeation chromatography in DMAc/LiCl with fluorescence/multiple-angle laser
      light scattering/refractive index detection, the method yields carbonyl profiles
      relative to the molecular weight of the cellulosic material. The derivatization
      procedure can be carried out either homogeneously in DMAc/LiCl or advantageously
      as heterogeneous derivatization in aqueous buffer. The heterogeneous carbonyl
      group determination, offering shorter reaction times and increased simplicity as
      compared to the homogeneous approach, was comprehensively validated. The carbonyl
      content in numerous dissolving pulps of different provenience has been
      determined, including pulps with carbonyl contents additionally increased by
      oxidative treatment. The method was also applied to follow bleaching sequences
      and oxidative treatments of pulps.

PMID- 12217043
TI  - Formation of polymerized mixed heparin/albumin surface layer and cellular
      adhesional responses.
AB  - The aim of this study was to create a dense albuminated layer, a heparinized
      layer, and a mixed layer on a poly(acrylic acid)-grafted surface via visible
      light induced photopolymerization. The procedure is comprised of four reaction
      steps: first, by visible light irradiation, acrylic acid (AA) was graft
      polymerized on a segmented polyurethane (SPU) film that was preimpregnated with
      camphorquinone. The second step was adsorption of multiply styrenated albumin or
      styrenated heparin or their mixture, followed by visible light irradiation in the
      presence of carboxylated camphorquinone. The third step was covalent bonding
      between polyAA graft chain and polymerized biomacromolecule and between
      polymerized biomacromolecule to enforce the formation of a stable immobilized
      multilayer. X-ray photoelectron spectroscopic and Fourier transform-infrared
      spectroscopic measurements were conducted to analyze the surfaces formed at each
      step. Confocal laser scanning microscopy was utilized to determine the thickness
      of the biomacromolecule-immobilized layer with several tenths of a micrometer
      thickness. Platelet adhesion was markedly reduced on polymerized albuminated,
      polymerized heparinized, and copolymerized layers, whereas adhesive and
      proliferative potentials of endothelial cells, which were comparable to those of
      commercial tissue culture dishes, were observed on these surfaces. Co
      immobilization of fibronectin and basic fibroblast growth factor enhanced these
      potentials. These densely multilayered surfaces may be suitable for artificial
      and tissue-engineered devices.

PMID- 12217044
TI  - Water-soluble fluorescent diblock nanospheres.
AB  - The hydroxyl groups of poly(tert-butyl acrylate)-block-poly(2-hydroxyethyl
      methacrylate) or PtBA-b-PHEMA were reacted with succinic anhydride to introduce
      some carboxyl groups into the PHEMA block. Such carboxyl groups were then reacted
      with Texas-red cadverine (TX-NH(2)) to incorporate dye molecules. The TX-bearing
      diblocks formed probably spherical micelles in block-selective solvent
      DMF/toluene containing 2% DMF. "Permanent" micelles or nanospheres were prepared
      after cross-linking the TX-bearing PHEMA core block. Such nanospheres were made
      water soluble by cleaving the tert-butyl groups from the PtBA coronas. Water
      soluble nanospheres with high TX numbers and fluorescence quantum yields may find
      applications in fluorescence in situ hybridization assays.

PMID- 12217045
TI  - (1)H NMR study of the states of water in equilibrium poly(HEMA-co-THFMA)
      hydrogels.
AB  - The spin-spin relaxation times, T(2), of hydrated samples of poly(hydroxymethyl
      methacrylate), PHEMA, poly(tetrahydrofurfuryl methacrylate), PTHFMA, and the
      corresponding HEMA-THFMA copolymers have been examined to probe the states of the
      imbibed water in these polymers. The decay in the transverse magnetization of
      water in fully hydrated samples of PHEMA, PTHFMA, and copolymers of HEMA and
      THFMA was described by a multiexponential function. The short component of T(2)
      was interpreted as water molecules that were strongly interacting with the
      polymer chains. The intermediate component of T(2) was assigned to water residing
      in the porous structure of the samples. The long component of T(2) was believed
      to arise from water residing in the remnants of cracks formed in the polymer
      network during water sorption.

PMID- 12217046
TI  - Galactosylated N-vinylpyrrolidone-maleic acid copolymers: synthesis,
      characterization, and interaction with lectins.
AB  - Water-soluble artificial glycoconjugate polymers were synthesized from poly(N
      vinylpyrrolidone-co-maleic anhydride) by amidation with an amine-containing
      galactose derivative. The glycopolymers having different galactose contents were
      fully characterized in terms of chemical structure by NMR and potentiometric
      titrations, and their aqueous behavior was studied by viscometric measurements.
      Their specific binding properties were examined by enzyme-linked lectin assays
      using RCA(120) lectin. Whatever the glycopolymer, the grafted galactoses were
      shown to behave similarly to free galactose.

PMID- 12217047
TI  - Biosynthesis and properties of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)
      polymers.
AB  - In support of programs to identify polyhydroxyalkanoates with improved materials
      properties, we report on our efforts to characterize the mechanical and thermal
      properties of copolyesters of 3-hydroxybutyrate (3HB) and 3-hydroxyhexanoate
      (3HHx). The copolyesters, having molar fraction of 3HHx ranging from 2.5 to 35
      mol % and average molecular weights ranging from 1.15 x 10(5) to 6.65 x 10(5),
      were produced by fermentation using Aeromonas hydrophila and a recombinant strain
      of Pseudomonas putida GPp104. The polymers were chloroform extracted and
      characterized by solution-state and solid-state nuclear magnetic resonance (NMR)
      spectroscopy and a variety of mechanical and thermal tests. Solution-state (1)H
      NMR data were used to determine polymer composition-of-matter, while solution
      state (13)C NMR data provided polymer-sequence information. Solvent fractionation
      and NMR spectroscopic characterization of these polymers showed that polymers
      containing up to 9.5 mol % 3HHx had a Bernoullian compositional distribution. By
      contrast, polymers containing more than 9.5 mol % 3HHx had a bimodal polymer
      composition. Solvent fractionation of these 3HHx-rich polyesters produced two
      polymer fractions, each of which was again consistent with Bernoullian
      polymerization statistics. Solid-state NMR relaxation experiments provided
      insight into aging in poly(3HB-co-3HHx) copolymers, demonstrating increased
      polymer-chain motion with increasing 3HHx content. The elongation-to-break ratio
      in the polyesters increased with increasing molar fraction of 3HHx monomers.
      Aging properties of the poly(3HB-co-3HHx) copolymers were very similar to
      copolymers of 3HB and 3-hydroxyvalerate (3HV). However, poly(3HB-co-3HHx)
      exhibited increased activation energy to thermal degradation with increasing 3HHx
      content.

PMID- 12217048
TI  - Formation of fibrin gel in fibrinogen-thrombin system: static and dynamic light
      scattering study.
AB  - The dynamics of thrombin-induced fibrin gel formation was investigated by means
      of static and dynamic light scattering. The decay time distribution function,
      obtained by the dynamic light scattering, clearly revealed a stepwise gelation
      process: the formation of fibrin and protofibril from fibrinogen followed by the
      lateral aggregation of protofibrils to form fibrin fibers and the formation of a
      three-dimensional network consisting of fibers. This conversion process was
      correlated with the angular dependence of the scattered light intensity (static
      light scattering). The correlation function of dynamic light scattering was
      analyzed in terms of sol-gel transition and gel structure. The correlation
      function showed a stretched exponential type behavior before the sol to gel
      transition point, and it showed a power law behavior at the gelation point.

PMID- 12217049
TI  - Stabilization of activity of oxidoreductases by their immobilization onto special
      functionalized glass and novel aminocellulose film using different coupling
      reagents.
AB  - Glucose oxidase (GOD), horseradish peroxidase (HRP), and lactate oxidase (LOD)
      were covalently immobilized on special NH(2)-functionalized glass and on a novel
      NH(2)-cellulose film via 13 different coupling reagents. The properties of these
      immobilized enzymes, such as activity, storage stability, and thermostability,
      are strongly dependent on the coupling reagent. For example, GOD immobilized by
      cyanuric chloride on the NH(2)-cellulose film loses approximately half of its
      immobilized activity after 30 days of storage at 4 degrees C or after treatment
      at 65 degrees C for 30 min. In contrast, GOD immobilized by L-ascorbic acid onto
      the same NH(2)-cellulose film retains 90% of its initial activity after 1 year of
      storage at 4 degrees C and 92% after heat treatment at 65 degrees C for 30 min.
      Unlike GOD, in the case of LOD only immobilization on special NH(2)
      functionalized glass, e.g., via cyanuric chloride, led to a stabilization of the
      enzyme activity in comparison to the native enzyme. The operational stability of
      immobilized HRP was up to 40 times higher than that of the native enzyme if
      coupling to the new NH(2)-cellulose film led to an amide or sulfonamide bond.
      Regarding the kinetics of the immobilized enzymes, the coupling reagent plays a
      minor role for the enzyme substrate affinity, which is characterized by the
      apparent Michaelis constant (K(M,app)). The NH(2)-functionalized support material
      as well as the immobilized density of the protein and/or immobilized activity has
      a strong influence on the K(M,app) value. In all cases, K(M,app) decreases with
      increasing immobilized enzyme protein density and particularly drastically for
      GOD.

PMID- 12217050
TI  - Synthesis and characterization of biodegradable cationic poly(propylene fumarate
      co-ethylene glycol) copolymer hydrogels modified with agmatine for enhanced cell
      adhesion.
AB  - We synthesized positively charged biodegradable hydrogels by cross-linking of
      agmatine-modified poly(ethylene glycol)-tethered fumarate (Agm-PEGF) and
      poly(propylene fumarate-co-ethylene glycol) (P(PF-co-EG)) to investigate the
      effect of the guanidino groups of the agmatine on hydrogel swelling behavior and
      smooth muscle cell adhesion to the hydrogels. The weight swelling ratio of these
      hydrogels at pH 7.0 increased from 279 +/- 4 to 306 +/- 7% as the initial Agm
      PEGF content increased from 0 to 200 mg/g of P(PF-co-EG), respectively. The
      diffusional exponents, n, during the initial phase of water uptake were
      independent of the initial Agm-PEGF content and were determined to be 0.66 +/-
      0.08, 0.71 +/- 0.07, and 0.60 +/- 0.05 for respective initial Agm-PEGF contents
      of 0, 100, and 200 mg/g. The heat of fusion of water present in the hydrogels
      increased from 214 +/- 11 to 254 +/- 4 J/g as the initial Agm-PEGF content
      increased from 0 to 200 mg/g. The number of adherent smooth muscle cells
      increased dose-dependently from 15 +/- 6 to 75 +/- 7% of the initial seeding
      density as the initial Agm-PEGF content increased from 0 to 200 mg/g. These
      results suggest that the incorporation of the guanidino groups of agmatine into
      P(PF-co-EG) hydrogels increases the hydrogel free water content and the total
      water content of the hydrogels and also enhances cell adhesion to the hydrogels.

PMID- 12217051
TI  - Synthesis and gelation of DOPA-modified poly(ethylene glycol) hydrogels.
AB  - 3,4-Dihydroxyphenylalanine (DOPA) residues are known for their ability to impart
      adhesive and curing properties to mussel adhesive proteins. In this paper, we
      report the preparation of linear and branched DOPA-modified poly(ethylene
      glycol)s (PEG-DOPAs) containing one to four DOPA endgroups. Gel permeation
      chromatography-multiple-angle laser light scattering analysis of methoxy-PEG-DOPA
      in the presence of oxidizing reagents (sodium periodate, horseradish peroxidase,
      and mushroom tyrosinase) revealed the formation of oligomers of methoxy-PEG-DOPA,
      presumably resulting from oxidative polymerization of DOPA endgroups. In the case
      of PEG-DOPAs containing two or more DOPA endgroups, oxidative polymerization
      resulted in polymer network formation and rapid gelation. The amount of time
      required for gelation of aqueous PEG-DOPA solutions was found to be as little as
      1 min and was dependent on the polymer architecture as well as the type and
      concentration of oxidizing reagent used. Analysis of reaction mixtures by UV-vis
      spectroscopy allowed the identification of reaction intermediates and the
      elucidation of reaction pathways. On the basis of the observed reaction
      intermediates, oxidation of the catechol side chain of DOPA resulted in the
      formation of highly reactive DOPA-quinone, which further reacted to form cross
      linked products via one of several pathways, depending on the presence or absence
      of N-terminal protecting groups on the PEG-DOPA. N-Boc protected PEG-DOPA cross
      linked via phenol coupling and quinone methide tanning pathways, whereas PEG-DOPA
      containing a free amino group cross-linked via a pathway that resembled
      melanogenesis. Similar differences were observed for the rate of gel formation as
      well as the molecular weight between cross-links ((-)M(c)), calculated using
      equilibrium swelling and the Flory-Rehner equation.

PMID- 12217052
TI  - Structure and properties of triolein-based polyurethane networks.
AB  - Polyurethane networks based on vegetable oils have very heterogeneous
      composition, and it is difficult to find a close correlation between their
      structure and properties. To establish benchmark structure-properties
      relationships, we have prepared model polyurethane networks based on triolein and
      4,4'-diphenylmethane diisocyanate (MDI). Cross-linking in the middle of fatty
      acid chains leaves significant parts of the triglyceride as dangling chains. To
      examine their effect on properties, we have synthesized another polyurethane
      network using triolein without dangling chains (removed by metathesis). The
      structure of polyols was studied in detail since it affects the structure of
      polyurethane networks. The network structure was analyzed from swelling and
      mechanical measurements and by applying network and rubber elasticity theories.
      The cross-linking density in both networks was found to be close to theoretical.
      The triolein-based model network displayed modulus (around 6 MPa), tensile
      strength (8.7 MPa), and elongation at break (136%), characteristic of hard
      rubbers. Glass transition temperatures of the networks from triolein and its
      metathesis analogue were 25 and 31.5 degrees C, respectively.

PMID- 12217053
TI  - One-step synthesis of amphiphilic diblock copolymers from bacterial poly([R]-3
      hydroxybutyric acid).
AB  - Catalyzed transesterification in the melt is used to produce diblock copolymers
      of poly([R]-3-hydroxybutyric acid), PHB, and monomethoxy poly(ethylene glycol),
      mPEG, in a one-step process. Bacterial PHB of high molecular weight is
      depolymerized by consecutive and partly simultaneous reactions: pyrolysis and
      transesterification. The formation of diblocks is accomplished by the
      nucleophilic attack from the hydroxyl end-group of the mPEG catalyzed by bis(2
      ethylhexanoate) tin. The resulting diblock copolymers are amphiphilic and self
      assemble into sterically stabilized colloidal suspensions of PHB crystalline
      lamellae.

PMID- 12217054
TI  - Glycosaminoglycan mimetic biomaterials. 4. Synthesis of sulfated lactose-based
      glycopolymers that exhibit anticoagulant activity.
AB  - Cyanoxyl persistent radicals can be used as chain-growth moderators of the
      statistical copolymerization of a variety of monomers. We report herein the
      preparation of fully sulfated lactose-based glycopolymers by cyanoxyl (.OC[triple
      bond]N)-mediated free-radical polymerization of acrylamide derivatized
      glycomonomers in good yield (60-80%) and low polydispersity (1.1 < M(w)/M(n) <
      1.6). Prolongation of the activated partial thromboplastin time (aPTT) was
      observed, and structure-activity relationships were defined. Specifically, the
      anticoagulant effect varied in response to both polymer molecular weight and the
      density of pendant sulfated lactose units. Nonetheless, measured thrombin times
      were only modestly prolonged suggesting that the observed anticoagulant effect is
      not primarily related to direct thrombin inhibition.

PMID- 12217055
TI  - Studies on comonomer compositional distribution of bacterial poly(3
      hydroxybutyrate-co-3-hydroxyhexanoate)s and thermal characteristics of their
      factions.
AB  - The comonomer-unit compositional distributions have been investigated for
      bacterial poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(3HB-co-3HH)] samples
      with 3HH unit content of 13.8, 18.0, 22.0, and 54.0 mol %. They were comonomer
      compositionally fractionated using chloroform/n-heptane mixed solvent at ambient
      temperature. The fractionation of P(3HB-co-18.0 mol %3HH) and P(3HB-co-22.0 mol %
      3HH), which could not be carried out effectively at room temperature, were
      refractionated at 70 degrees C in the mixed solvent. Fractions with different 3HH
      unit content in a wide range (from 4.4 to 80.7 mol %) were obtained. By use of
      these fractions with narrow compositional distribution, the comonomer composition
      dependence of thermal properties was investigated by differential scanning
      calorimetry. The melting point (T(m)) and heat of fusion (DeltaH) decreased as
      the 3HH unit content increased in the range of low 3HH content (<40 mol %), while
      they increased as the 3HH unit content increased in the high 3HH content range
      (>70 mol %). The minimum T(m) and DeltaH values were found to exist at 3HH unit
      content of about 60 mol %. The glass transition temperature (T(g)) decreased
      linearly with the increase of 3HH unit content. The values of T(m), DeltaH, and
      T(g) of P(3HB-co-3HH)s were compared with those of poly(3-hydroxybutyrate-co-3
      hydroxyvalerate), poly(3-hydroxybutyrate-co-3-hydroxypropionate), and poly(3
      hydroxybutyrate-co-4-hydroxybutyrate), and the effects of comonomer types on the
      thermal properties were revealed.

PMID- 12217056
TI  - Poly(alpha-alkyl gamma-glutamate)s of microbial origin. 2. On the microstructure
      and crystal structure of poly(alpha-ethyl gamma-glutamate)s.
AB  - The stereochemical microstructure and crystalline structure of nearly racemic
      poly(alpha-ethyl gamma,DL-glutamate) obtained by esterification of biosynthetic
      poly(gamma-glutamic acid) were examined by NMR, DSC, and powder X-ray
      diffraction. The two enantiomerically pure poly(alpha-ethyl gamma-glutamate)s, as
      well as the racemic stereocopolymers with random and alternating microstructure,
      were prepared by chemical synthesis and studied in parallel to help in the
      interpretation of the data. The (13)C NMR analysis revealed that biosynthetic
      poly(alpha-ethyl gamma,DL-glutamate) consists of a block stereocopolymer
      accompanied by minor amounts of a mixture of the two optically pure homopolymers.
      The polymer is crystalline, with a degree of crystallinity and crystal structure
      essentially similar to those displayed by the optically pure polymers but clearly
      different from the alternating copolymer. Conversely, the racemic stereocopolymer
      with a random microstructure prepared by chemical synthesis is amorphous. The
      crystal structure of the racemic mixture of the D- and L-homopolymers seems to be
      very close to that of the biosynthetic stereocopolymer, although some indications
      suggesting the existence of a stereocomplex were found.

PMID- 12217057
TI  - Graft copolymerization of ethyl acrylate onto cellulose using ceric ammonium
      nitrate as initiator in aqueous medium.
AB  - Ceric ammonium nitrate (CAN) in the presence of nitric acid has been used as
      efficient initiator for graft copolymerization of the ethyl acrylate onto
      cellulose at 35.0 +/- 0.1 degrees C. Graft copolymerization of ethyl acrylate
      onto cellulose has taken place through the radical initiation process. The graft
      yield and other grafting parameters have been evaluated by varying concentration
      of ethyl acrylate from 2.5 x 10(-1) to 15.0 x 10(-1) mol dm(-3) and ceric
      ammonium nitrate from 5.0 x 10(-3) to 25.0 x 10(-3) mol dm(-3) at constant
      concentration of the nitric acid (8.0 x 10(-2) mol dm(-3)). The rate of graft
      copolymerization has shown 1.5 order with respect to the concentration of the
      ceric ammonium nitrate. The graft copolymerization data obtained at different
      temperatures were used to calculate the energy of activation, which has been
      found to be 28.9 kJ mol(-1) within the temperature range from 20 to 50 degrees C.
      The effect of addition of cationic and anionic surfactants on graft
      copolymerization has also been studied. On the basis of the experimental
      observations, reaction steps have been proposed and a suitable rate expression
      for graft copolymerization has been derived.

PMID- 12217058
TI  - Molecular mobility and phase structure of biodegradable poly(butylene succinate)
      and poly(butylene succinate-co-butylene adipate).
AB  - Molecular mobility and phase structure of biodegradable poly(butylene succinate)
      (PBS) and poly(butylene succinate-co-20 mol % butylene adipate) [P(BS-co-20 mol %
      BA)] have been investigated by high-resolution solid-state (13)C NMR. For both
      samples, two components with different (13)C spin-lattice relaxation time (T(1C))
      values have been observed in the crystalline region. The crystalline component
      with shorter T(1C) value is assignable to the interface near amorphous phase. The
      crystalline component with longer T(1C) value is ascribed to the inside of the
      crystalline region. On the basis of T(1C), it has been concluded that the BA
      units are not included in the crystalline region of P(BS-co-20 mol % BA).
      Molecular mobility and higher-ordered structure of amorphous phase have been also
      compared between the melt and solid state. Variable-temperature high-resolution
      (13)C NMR measurements for the amorphous phase have revealed the remarkable
      difference in dynamics and structure between the melt and solid state.

PMID- 12217059
TI  - Plasticized waxy maize starch: effect of polyols and relative humidity on
      material properties.
AB  - The plasticizing effect of different polyols such as glycerol, xylitol, sorbitol,
      and maltitol on waxy maize starch was investigated. The concentration of
      plasticizer was fixed at 33 wt % (dry basis of starch). The structure and
      mechanical performance of resulting films conditioned at different relative
      humidity levels were studied in detail. The effect of the plasticizer on the
      glass-rubber transition temperature (T(g)) and crystallinity was characterized
      using differential scanning calorimetry. It was found that T(g) decreases with
      increasing moisture content and decreasing molecular weight of the plasticizer.
      The water resistance of starch increased steadily with the molecular weight of
      the plasticizer and was directly proportional to the ratio of the end to total
      hydroxyl groups. As the molecular weight of the plasticizer increased, the
      brittleness of the dry system increased. However, the use of high molecular
      plasticizer allowed good mechanical properties of the moist material to be
      obtained in terms of both stiffness and elongation at break.

PMID- 12217060
TI  - Stereocomplex formation by enantiomeric poly(lactic acid) graft-type phospholipid
      polymers for tissue engineering.
AB  - A porous scaffold as a cell-compatible material was designed and prepared using a
      phospholipid copolymer composed of 2-methacryloyloxyethyl phosphorylcholine
      (MPC), n-butyl methacrylate, and enantiomeric macromonomers, the poly(L-lactic
      acid) (PLLA) macromonomer, and poly(D-lactic acid) (PDLA) macromonomer. On the
      basis of the wide-angle X-ray diffraction and differential scanning calorimetry
      measurements, the formation of a stereocomplex between the PLLA and PDLA segments
      of the copolymer was observed on the porous scaffold. The porous structure was
      prepared by a sodium chloride leaching technique, and the pore was linked to the
      scaffold. The pore size was confirmed by scanning electron microscopy and found
      to be ca. 200 microm. These observations suggest that the porous scaffold makes
      it possible to produce cell-compatible materials, which may involve the following
      advantages for tissue engineering: (i) cell compatibility using phospholipid
      copolymer, (ii) adequate cell adhesion by poly(lactic acid), and (iii) complete
      disappearance of scaffold by dissociation of stereocomplex. The cell experiment
      using the porous scaffold will be the next subject and reported in a forthcoming
      paper.

PMID- 12217061
TI  - Biodegradable polymeric nanospheres formed by temperature-induced phase
      transition in a mixture of poly(lactide-co-glycolide) and poly(ethylene oxide)
      poly(propylene oxide)-poly(ethylene oxide) triblock copolymer.
AB  - The mixture of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)
      triblock copolymer(F-127) and PLGA (poly(lactide-co-gycolide)) forms a liquid
      state above their phase transition temperatures, and the phase-separated state is
      induced by decreasing the temperature below the phase transition temperature. On
      the basis of the temperature-induced phase transition behavior in the mixture of
      F-127 and PLGA, a novel method for the preparation of drug-loaded PLGA
      nanospheres was designed and characterized by measuring the loading amount, the
      encapsulation efficiency, and the drug release pattern. Paclitaxel, used as a
      potent anticancer drug, was selected as a model drug.

PMID- 12217062
TI  - Chemical modification of chitosan. 13.(1) Synthesis of organosoluble, palladium
      adsorbable, and biodegradable chitosan derivatives toward the chemical plating on
      plastics.

PMID- 12217063
TI  - Chemical modification of chitosan. 14:(1) Synthesis of water-soluble chitosan
      derivatives by simple acetylation.

PMID- 12217064
TI  - Editorial independence is built on trust and communication.

PMID- 12217065
TI  - Professional responsibility in relation to cervical spine manipulation.
AB  - Manipulation of the cervical spine is one of the few potentially life-threatening
      procedures performed by physiotherapists. Is it worth the risk? A comparison of
      risks versus benefits indicates that at present, the risks of cervical
      manipulation outweigh the benefits: manipulation has yet to be shown to be more
      effective for neck pain and headache than other interventions such as
      mobilisation, whereas the risks, although infrequent, are serious. This analysis
      is of particular concern because the conditions for which manipulation is
      indicated are benign and usually self-limiting. Because physiotherapists have
      legal and ethical obligations to the community to avoid foreseeable harm and
      provide optimum care, it may be prudent to determine who in our profession should
      perform cervical manipulation. That is, the profession could restrict the
      practice of cervical spine manipulation. Although all registered physiotherapists
      in Australia are entitled to perform cervical manipulation, few choose to use
      this intervention. Therefore, it might be feasible to encourage those
      practitioners who wish to use cervical manipulation to undertake formal education
      programs. Such a requirement could be embodied in a code of practice that
      discourages those without formal training from performing cervical manipulation.
      By taking such measures, we could ensure that our profession exercises wisdom in
      its monitoring and use of cervical manipulation.

PMID- 12217068
TI  - Use of high and low velocity cervical manipulative therapy procedures by
      Australian manipulative physiotherapists.
AB  - The use of cervical manipulation presents concerns because of a risk of
      devastating side effects of trauma to the vertebral artery. Little is known about
      the frequency of use of cervical manipulation versus passive mobilisation by
      physiotherapists. A recent national, multi-centre randomised clinical trial of
      the physiotherapy management of cervicogenic headache provided an opportunity to
      gain an insight into practices of a sample of manipulative physiotherapists
      across Australia. The treatment records for the 100 subjects who received only
      manipulative therapy, or manipulative therapy with exercise as per the trial
      protocol, were audited. The results revealed that cervical manipulation was used
      in 20.2% of the 1090 treatments provided to these subjects but cervical joint
      mobilisation only was used in the vast majority of treatments (77.6%).
      Nevertheless, 42% of subjects were treated with cervical manipulation at some
      time. In most instances, manipulation was accompanied by passive mobilisation in
      the same treatment session. Patients were manipulated on one to six occasions and
      this occurred predominantly in the latter half of the 12-treatment program.
      Cervical manipulation was used less frequently in the group who also received
      exercise. The data suggest that the physiotherapists participating in this study
      used cervical manipulation selectively and relatively conservatively considering
      the high use of cervical mobilisation techniques. This may reflect their due
      regard to safety in the treatment of the cervical region.

PMID- 12217069
TI  - The effect of scapula taping on electromyographic activity and musical
      performance in professional violinists.
AB  - Taping the scapula has been suggested as a method of improving both scapula
      position and muscular efficiency of the shoulder girdle. These factors have been
      linked to neck and arm problems in violinists. The purpose of this study was to
      evaluate the effects of taping the scapulae of violinists into a position that
      prevented excessive elevation and protraction whilst playing. Eight professional
      violinists played three different musical excerpts with and without scapula
      taping applied in random order. Electromyographic activity was recorded from the
      upper trapezii, the scapula retractors and the right sternocleidomastoid muscles.
      Performances were recorded onto videotape and audiocassette, and self-report data
      collected for later analysis. Compared with the control condition, scapula taping
      increased electromyographic activity in the left upper trapezius muscle during
      playing by 49% as an overall effect, with a 60% increase in the most physically
      demanding piece played. Lower music quality was detected in the same piece by
      raters blinded to performance conditions. Taping also had significant negative
      effects on subjects' reports of concentration and comfort. Short-term application
      of scapula taping did not enhance selected scapula stabilising muscles during
      playing and was not well tolerated by professional violinists.

PMID- 12217070
TI  - The effect of huffing and directed coughing on energy expenditure in young
      asymptomatic subjects.
AB  - Coughing and huffing have been shown to be effective airway clearance techniques
      and some authors have anecdotally reported that a huff requires less energy than
      a series of coughs commencing and finishing at the same lung volume. The aim of
      this study was to determine whether there is a difference in the energy
      expenditure between periods of huffing and directed voluntary coughing commencing
      from the same initial lung volume in young asymptomatic subjects. Energy
      expenditure was measured using open-circuit indirect calorimetry equipment.
      Twenty-four non-smoking asymptomatic subjects (12 male, 12 female, aged 18-24
      years), without any form of disease and within 10% of their predicted pulmonary
      function, completed the study. Energy expenditure was measured over three 10min,
      randomly ordered sessions of huffing, directed coughing and rest. The forced
      expiratory sessions comprised a single huff or double-barrel cough (both starting
      at total lung capacity) at the end of every two minutes. Each session was
      separated by a 5min washout period. No significant difference in energy
      expenditure was found between the huffing and directed coughing periods (mean
      difference 0.003 mL/kg/min (95% CI -0.160 to 0.114) and both produced
      significantly greater energy expenditure than rest (rest and huff mean difference
      0.309 mL/kg/min (95% CI 0.080 to 0.549) and rest and cough mean difference 0.306
      mL/kg/min (95% CI 0.074 to 0.508)). The suggested benefits of huffing versus
      coughing in terms of energy conservation are yet to be shown.

PMID- 12217071
TI  - A comparison of community-based resistance exercise and flexibility exercise for
      seniors.
AB  - Progressive resistance training has positive effects on the health of elderly
      people, however exercise programs for seniors frequently focus on other forms of
      exercise. This study is a randomised trial with a blinded assessor comparing a
      community based progressive resistance training program (n = 20) with a
      flexibility program (n = 20), both one hour twice weekly for 10 weeks. Outcomes
      were strength, gait, balance and quality of life. Progressive resistance training
      had a greater effect than flexibility training on right sided quadriceps strength
      (mean difference between groups = 7.7%; 95% CI 3.6-11.8%, p < 0.003 MANOVA), left
      sided quadriceps strength (mean difference = 9.9%; 95% CI 5.6-14.2%, p < 0.003
      MANOVA), left sided biceps strength (mean difference = 15.2%; 95% CI 11.7-19.2%,
      p < 0.003 MANOVA), functional reach (mean difference = 11.7%; 95% CI 7.1-16.3%, p
      < 0.003 MANOVA) and step test (mean difference = 8.6%; 95% CI 3.8-13.4%, p <
      0.003 MANOVA). Neither group had improvements in SF36 quality of life measures.
      Results suggest progressive resistance training produces greater strength, gait
      and balance improvements in elderly people than a flexibility exercise program.

PMID- 12217072
TI  - WorkCover's physiotherapy forms: purpose beyond paperwork?
AB  - We retrospectively analysed 219 consecutive treatment plans submitted to a large
      New South Wales workers' compensation insurer for workers coded by the insurer as
      suffering from back pain. The purpose was to (i) describe the quality of goals of
      treatment provided to insurers by physiotherapists for workers with back pain
      using guidelines provided by the WorkCover Authority of New South Wales
      (WorkCover); (ii) compare the physiotherapists' prognoses against prognoses
      indicated in clinical practice guidelines; and (iii) make recommendations about
      the communication system between physiotherapists and insurers. The back pain of
      most treated workers was classified as acute and the majority of physiotherapists
      estimated that treatment would be of short duration, which is concordant with
      current treatment guidelines. However, most physiotherapists did not provide
      precise, measurable or time-specific treatment goals, despite this being
      emphasised by WorkCover. We propose ways of improving communication practices
      between physiotherapists and insurers.

PMID- 12217073
TI  - The interpretation of diagnostic test: a primer for physiotherapists.
AB  - This paper outlines a practical approach to assist physiotherapists to interpret
      the results of diagnostic or screening tests. Diagnostic tests are used during
      clinical assessment to increase or decrease the clinician's estimate of the
      likelihood that a client has a particular condition. A negative result for a test
      that is 100% sensitive can rule a condition out (SnOUT), and a positive result
      for a test that is 100% specific can rule a condition in (SpIN). However, tests
      are rarely 100% accurate, and false-positive and false-negative results can
      occur. The examining therapist needs to estimate the probability that a client
      has a particular condition (the pre-test probability), then estimate the extent
      to which they are more or less certain given a positive or negative test result
      (the post-test probability). The likelihood ratio, which combines the information
      provided by a test's sensitivity and specificity, is the most useful tool for the
      clinical interpretation of test results.

PMID- 12217074
TI  - Bed exercises result in decreased pain with functional activities following hip
      arthroplasty. (Comment on Jesudason C and Stiller K, Australian Journal of
      Physiotherapy 48: 73-81.).

PMID- 12217076
TI  - The thylakoid membrane protein ALB3 associates with the cpSecY-translocase in
      Arabidopsis thaliana.
AB  - The integration of light-harvesting chlorophyll proteins (LHCPs) into the
      thylakoid membrane requires the integral thylakoid membrane protein ALB3, a
      homologue of the bacterial cytoplasmic membrane protein YidC. In bacteria, YidC
      is associated with the SecY-translocase and facilitates the integration of Sec
      dependent proteins into the plasma membrane. In addition, it is also involved in
      the insertion of Sec-independent proteins. In the present study we demonstrate,
      in Arabidopsis thaliana, that most ALB3 is a constituent of an oligomeric complex
      of approx. 180 kDa. In addition, we detected ALB3 in several higher-molecular
      mass complexes (up to 700 kDa). Furthermore, we show that most ALB3 co
      fractionates with cpSecY during gel-filtration analysis and blue native gel
      electrophoresis, suggesting an association of ALB3 with the cpSecY complex. A
      direct interaction of ALB3 with the cpSecY complex was demonstrated by co
      immunoprecipitation experiments using digitonin-solubilized thylakoid membrane
      proteins and anti-cpSecY or anti-ALB3 antibodies. This result was further
      confirmed by electron microscopic co-immunolocalization of ALB3 and cpSecY. In
      addition, an association of ALB3 with the cpSecY complex was demonstrated
      directly by cross-linking experiments using the chemical cross-linker
      disuccinimidyl suberate.

PMID- 12217077
TI  - Solution structure of a chemosensory protein from the moth Mamestra brassicae.
AB  - Chemosensory proteins (CSPs) are believed to be involved in chemical
      communication and perception. A number of such proteins, of molecular mass
      approximately 13 kDa, have been isolated from different sensory organs of a wide
      range of insect species. Several CSPs have been identified in the antennae and
      proboscis of the moth Mamestra brassicae. CSPMbraA6, a 112-amino-acid antennal
      protein, has been expressed in a soluble form in large quantities in the
      Escherichi coli periplasm. NMR structure determination of CSPMbraA6 has been
      performed with 1H- and 15N-labelled samples. The calculated structures present an
      average root mean square deviation about the mean structure of 0.63 A for
      backbone atoms and 1.27 A for all non-hydrogen atoms except the 12 N-terminal
      residues. The protein is well folded from residue 12 to residue 110, and consists
      of a non-bundle alpha-helical structure with six helices connected by alpha alpha
      loops. It has a globular shape, with overall dimensions of 32 A x 28 A x 24 A. A
      channel is visible in the hydrophobic core, with dimensions of 3 A x 9 A x 21 A.
      In some of the 20 solution structures calculated, this channel is closed either
      by Trp-94 at one end or by Tyr-26 at the other end; in some other solutions, this
      channel is closed at both ends. Binding experiments with 12-bromododecanol
      indicate that the CSPMbraA6 structure is modified upon ligand binding.

PMID- 12217078
TI  - Regulation of the 14-3-3-binding protein p39 by growth factors and nutrients in
      rat PC12 pheochromocytoma cells.
AB  - Unstimulated PC12 pheochromocytoma cells contain many proteins that bound to 14-3
      3s in competition with a 14-3-3-binding peptide. Additional proteins, including
      one of 39 kDa (p39), became capable of binding to 14-3-3s in phosphatidylinositol
      3-kinase-dependent responses to epidermal growth factor or nerve growth factor in
      vivo. The growth factor regulation was unaffected by inhibitors of the mitogen-
      or stress-activated protein kinase pathways, or by glucose starvation, but was
      blocked by amino acid starvation and only partially blocked by rapamycin. p39 in
      extracts of unstimulated, nutrient-fed cells, but not nutrient-starved cells, was
      able to bind to 14-3-3s after phosphorylation by protein kinase B (PKB) in vitro.
      Nutrient starvation did not affect the growth factor-stimulated activation of PKB
      in vivo. Either cycloheximide (CHX) or the cysteine protease inhibitor, MG132,
      restored the responsiveness of p39 to growth factors in nutrient-starved cells.
      In contrast, MG132 could not replace amino acids in supporting the growth factor
      stimulated phosphorylation of two downstream targets of mTOR (mammalian target of
      rapamycin), namely eukaryotic initiation factor 4E binding protein 1 (4E-BP1) and
      p70 S6 kinase. CHX permitted complete growth factor-stimulated phosphorylation of
      both 4E-BP1 and p70 S6 kinase in nutrient- starved cells; however, unlike p39,
      phosphorylation of these proteins was blocked by rapamycin. These findings
      implicate PKB (or an enzyme with similar specificity) in the growth factor
      triggered phosphorylation of p39. In addition, amino acid starvation induces a
      CHX- and MG132-sensitive pathway that targets p39 and appears to be distinct from
      the mechanism of regulation of 4E-BP1 and p70 S6 kinase.

PMID- 12217079
TI  - Efficacy and adverse effects of intravenous lignocaine therapy in fibromyalgia
      syndrome.
AB  - BACKGROUND: To investigate the effects of intravenous lignocaine infusions (IV
      lignocaine) in fibromyalgia. METHODS: Prospective study of the adverse effects of
      IV lignocaine in 106 patients with fibromyalgia; retrospective questionnaire
      study of the efficacy of IV lignocaine in 50 patients with fibromyalgia. RESULTS:
      Prospective study: Two major (pulmonary oedema and supraventricular tachycardia)
      and 42 minor side-effects were reported. None had long-term sequelae. The
      commonest was hypotension (17 cases). Retrospective study: Pain and a range of
      psychosocial measures (on single 11-point scales) improved significantly after
      treatment. There was no effect of the treatment on work status. The average
      duration of pain relief after the 6-day course of treatment was 11.5 +/- 6.5
      weeks. CONCLUSIONS: Intravenous lignocaine appears to be both safe and of benefit
      in improving pain and quality of life for patients with fibromyalgia. This needs
      to be confirmed in prospective randomised controlled trials.

PMID- 12217080
TI  - Antibiotics for coughing in general practice: a questionnaire study to quantify
      and condense the reasons for prescribing.
AB  - BACKGROUND: Antibiotics are being overprescribed in ambulant care, especially for
      respiratory tract infections (RTIs). Gaining insight into the actual reasons for
      prescribing remains important for the design of effective strategies to optimise
      antibiotic prescribing. We aimed to determine items of importance for the
      antibiotic prescribing decision and to make them operational for an intervention
      trial. METHODS: A postal questionnaire based upon focus group findings was sent
      to 316 Flemish general practitioners (GPs). On a verbal rating scale the GPs
      scored to what extent they consider the questionnaire items in decision making in
      case of suspected RTI in a coughing patient and how strongly the items support or
      counter antibiotic treatment. Factor analysis was used to condense the data. The
      relative importance of the yielded operational factors was assessed using
      Wilcoxon Matched Pairs test. RESULTS: 59.5% completed the study. Response group
      characteristics (mean age: 42.8 years; 65.9% men) approximated that of all
      Flemish GPs. Participants considered all the items included in the questionnaire:
      always the operational factor 'lung auscultation', often 'whether or not there is
      something unusual happening' - both medical reasons - and to a lesser extent 'non
      medical reasons' (P < 0.001). Non-medical as well as medical reasons support
      antibiotic treatment, but non-medical reasons to a lesser extent (P < 0.001).
      CONCLUSION: This study quantified, condensed and confirmed the findings of
      previous focus group research. Practice guidelines and interventions to optimise
      antibiotic prescribing have to take non-medical reasons into account.

PMID- 12217082
TI  - Driving on the motorway: the effect of alternating speed on driver's activation
      level and mental effort.
AB  - When most of the driving tasks are performed automatically, a driver's level of
      alertness may decline, as has been pointed out in the study of the phenomenon
      called 'highway hypnosis'. One possible countermeasure is to periodically vary
      the speed (Wertheim 1978), but the authors have not found any studies that
      directly assess the effectiveness of this countermeasure. The objective of our
      study has been to provide empirical evidence regarding the effects of this
      strategy on the level of driver activation on a motorway route in real traffic.
      In the present study activation level as indexed by a relative measure based on
      slow EEG activity tended to be significantly higher when speed was modified
      periodically than when it remained constant. In addition, this index tended to be
      progressively higher when the speed was constant during the first part of the
      route, while the same thing did not occur when the speed was modified
      periodically. Finally, no significant differences between the constant and
      varying speed conditions were obtained with respect to any of the cardiovascular
      indices related to the effort put into driving and the stress experienced in the
      situation.

PMID- 12217081
TI  - Carbon and nitrogen substrate utilization by archival Salmonella typhimurium LT2
      cells.
AB  - BACKGROUND: A collection of over 20,000 Salmonella typhimurium LT2 mutants,
      sealed for four decades in agar stabs, is a unique resource for study of genetic
      and evolutionary changes. Previously, we reported extensive diversity among
      descendants including diversity in RpoS and catalase synthesis, diversity in
      genome size, protein content, and reversion from auxotrophy to prototrophy.
      RESULTS: Extensive and variable losses and a few gains of catabolic functions
      were observed by this standardized method. Thus, 95 catabolic reactions were
      scored in each of three plates in wells containing specific carbon and nitrogen
      substrates. CONCLUSION: While the phenotype microarray did not reveal a distinct
      pattern of mutation among the archival isolates, the data did confirm that
      various isolates have used multiple strategies to survive in the archival
      environment. Data from the MacConkey plates verified the changes in carbohydrate
      metabolism observed in the Biolog system.

PMID- 12217083
TI  - Pathomechanisms of work-related musculoskeletal disorders: conceptual issues.
AB  - Work-related musculoskeletal disorders (WRMSDs) by definition are a subset of
      musculoskeletal disorders (MSDs) that arise out of occupational exposures. While
      traditional exposure assessment techniques have proved to be successful in
      identifying ergonomic exposures that are epidemiologically linked to these
      disorders, some are troubled by the lack of one-to-one correspondence between
      specific occupational exposure profiles and specific MSDs. In the absence of more
      sophisticated hypotheses that might explain the occurrence of WRMSDs in a variety
      of exposure patterns, the aetiologic relationships may (again) be called into
      question. Another unanswered question is whether specific types of WRMSDs have
      qualitatively different exposure-response relationships. A clearer understanding
      of the underlying pathomechanisms associated with specific WRMSDs could help
      future researchers better determine how and when various occupational exposure
      profiles become pathogenic. Such knowledge could also be used to design exposure
      assessment tools to capture exposure information more relevant to the risk of
      WRMSDs. The main goals of this paper are to summarize several recently described
      pathomechanisms, most of which have been discussed primarily in clinical and
      experimental literature that might not be widely read by occupational health
      scientists. Suggestions are made as to how future research could evaluate whether
      these phenomena are relevant to the effects of physical exposures and the
      underlying disease processes of common WRMSDs.

PMID- 12217084
TI  - Cardiorespiratory and efficiency responses during arm and leg exercises with
      spontaneously chosen crank and pedal rates.
AB  - The aim of this study was to compare the cardiorespiratory and efficiency
      responses between upper (T(UBE)) and lower (T(LBE)) body exercises at the same
      relative power outputs and with spontaneously chosen crank (SCCR) or pedal (SCPR)
      rates. Twelve participants performed exercise bouts set at 20, 40, 60 and 80% of
      maximal power (MP) separated by passive recovery periods. Oxygen uptake,
      ventilation, gross and work efficiencies during T(LBE) were significantly (P <
      0.05) higher than during T(UBE). These results suggest that these responses were
      not directly related to the relative intensities. However, no significant
      difference was found for delta efficiency and heart rate values. During T(UBE)
      and T(LBE), gross efficiency increased significantly (P < of MP for T(UBE) and
      T(LBE) and the same SCCR and SCPR could explain these results. The present
      results confirm that the cardiorespiratory and efficiency responses between arm
      and leg exercises are not always similar, although the power output are
      normalized in relation to MP and add to the understanding of differences between
      upper and lower body.

PMID- 12217085
TI  - An examination of the relationship between cycle training, cycle accidents,
      attitudes and cycling behaviour among children.
AB  - Around 40% of 10-11-year-old children receive cycle training every year in the
      UK, but concern has been expressed over the efficacy of training courses. One
      argument is that accidents occur too infrequently to be a viable evaluative
      criterion, and attitudes and behaviour have been suggested as alternatives. A
      questionnaire that measured a number of variables including accidents, attitudes,
      and behaviour was completed by 336 participants from two schools in the London
      Borough of Bromley. At least one cycling injury had been sustained by 58.3% of
      respondents, requiring hospital treatment in 19.1% of cases. Girls reported fewer
      accidents than boys. No relationship between training and accidents was found. A
      principal components analysis (PCA) of the attitudes items produced a 'safe
      attitudes' factor. Girls displayed 'safer' attitudes, but there was no evidence
      that training produced safer attitudes. A PCA of the cycling behaviour scales
      produced two factors, 'safe cycling' and 'showing off'. Safe cyclists who obeyed
      basic safety rules were less likely to sustain cycle injuries, but showing off
      was not related to accidents. Girls were less likely to show off, but the safe
      behaviour gender difference did not reach significance. Training did not relate
      to either factor.

PMID- 12217086
TI  - Functional Neuromuscular Stimulation for articular angle control with an Inverse
      Dynamics Model tuned by a neural network.
AB  - A Functional Neuromuscular Stimulation (FNS) system was developed to restore the
      motor function of people with central nervous system disorders. An FNS articular
      angle control system with an Inverse Dynamics Model (IDM) tuned by a neural
      network was proposed. The system was designed to control the elbow joint angles
      by learning the characteristics of the neuromuscular system of controlled limbs.
      Three kinds of control schemes using the IDM were proposed. In a simulation
      experiment, the system was able to learn the abnormal characteristics of a limb
      and any changes in these characteristics, and then allow for better control of
      the limb. The results of experiments using human participants showed that the
      system had ability to control both normal and paralysed limbs.

PMID- 12217088
TI  - Younger people in dementia care: a review of service needs, service provision and
      models of good practice.
AB  - This paper reviews the literature on younger people (under 65 years of age) with
      dementia, in dementia care. Seventy-four relevant papers were identified by use
      of a search strategy derived from the methodology of systematic reviews, the
      majority of which originated in the UK (69, 93.2%). The need for specialist,
      flexible, age-appropriate, and dedicated services was a central theme in the
      literature. A person-centred approach was advocated within an individual or
      'tailor made' model of care. However, the available evidence suggests that this
      model of good practice is not currently reflected in the majority of services
      provided in the United Kingdom. Overall, the literature argues that the needs of
      younger people with dementia are best served by inter-agency collaboration, early
      assessment, and an awareness of individual needs. Clearly, these proposals could
      usefully serve anybody with dementia, irrespective of age. However, aside from a
      few prevalence studies, and some exploratory work with small numbers of service
      users, little in the way of empirical work is available. The recommendations that
      have been made regarding dementia services for younger people are based largely
      on the practical experience of professionals and paid carers, rather than
      scientific evidence.

PMID- 12217089
TI  - A randomized controlled trial of the psychosocial impact of providing internet
      training and access to older adults.
AB  - The Internet (electronic mail and the World Wide Web) may provide new
      opportunities for communication that can help older adults avoid social
      isolation. This randomized controlled trial assessed the psychosocial impact of
      providing Internet access to older adults over a five-month period. One hundred
      volunteers from four congregate housing sites and two nursing facilities were
      randomly assigned to receive Internet training or to a wait list control group.
      The pre & post measures included the UCLA Loneliness scale, modified CES
      Depression scale, a measure of locus of control, computer attitudes, number of
      confidants, and overall quality of life. Participants received nine hours of
      small group training in six sessions over two weeks. Computers were available for
      continued use over five months and the trainer was available two hours/week for
      questions. At the end of the trial, 60% of the intervention group continued to
      use the Internet on a weekly basis. Although there was a trend toward decreased
      loneliness and depression in intervention subjects compared to controls, there
      were no statistically significant changes from baseline to the end of trial
      between groups. Among Internet users (n = 29) in the intervention group there
      were trends toward less loneliness, less depression, more positive attitudes
      toward computers, and more confidants than among intervention recipients who were
      not regular users (n = 19) of this technology. Most elderly participants in this
      trial learned to use the Internet and the majority continued to use it on a
      weekly basis. The psychosocial impact of Internet use in this sample suggested
      trends in a positive direction. Further research is needed to determine more
      precisely, which older adults, residing in which environmental contexts are more
      likely than others to benefit from this rapidly expanding information and
      communication link.

PMID- 12217090
TI  - Physical activity and physique anxiety in older adults: fitness, and efficacy
      influences.
AB  - Employing a randomized controlled trial, this study documents the effects of six
      months of physical activity and six month follow-up on reduction in social
      physique anxiety (SPA) in older adults. In addition, the role played by changes
      in behavioral, physiological, and psychological predictors of changes in SPA were
      examined. Participants (n = 174, mean age = 65 yrs) were randomly assigned to one
      of two activity groups and engaged in a six-month structured exercise program.
      Measures of physique anxiety were taken at baseline, six and twelve months.
      Latent growth curve analyses revealed significant reductions in SPA over the
      course of the 12-month period. Structural analyses controlling for treatment
      condition indicated that improvements in self-efficacy and fitness were
      significant predictors of changes in SPA but that changes in body fat and
      exercise frequency did not contribute to variation in SPA. Overall this model
      accounted for 19% of the variation in SPA changes. The extent to which changes in
      SPA may contribute to continued physical activity participation in older adults
      and how exercise programs might effectively influence predictors of SPA are
      discussed.

PMID- 12217091
TI  - Measuring aggression in older adults: a latent variable modeling approach.
AB  - This cross-sectional measurement study demonstrates a technique for combining
      information from several aggression scales into one aggression score using latent
      variable modeling. Participants included male patients (n = 49) with a DSM-IV
      diagnosis of dementia at The Veterans Affairs Medical Center Outpatient Geriatric
      Psychiatry Clinic. Data from seven aggression scales were used to indicate the
      latent aggression variable. Results provided evidence that a unidimensional
      latent variable model of aggression adequately represented the data. Reliability
      of the aggression latent variable was estimated as 0.90, whereas reliability of
      the separate scales estimated with this sample were less than 0.84. Our findings
      suggest that combining multiple scales into one aggression score using latent
      variable modeling results in comprehensive and reliable aggression scores that
      offer researchers several advantages over current methods for measuring
      aggression.

PMID- 12217092
TI  - The process of a group intervention for caregivers of demented persons living at
      home: conceptual framework, components, and characteristics.
AB  - Most earlier group interventions for caregivers of demented persons lacked a
      theoretical basis to guide the intervention process and focused on providing
      information and practical advice and encouraging the expression of feelings. This
      article presents the process of a group intervention with emphasis on its
      conceptual framework, components and characteristics. As caregivers are exposed
      to numerous daily stressful demands, the intervention's conceptual framework was
      derived from Lazarus and Folkman's transactional theory of stress and coping and
      Folkman's Coping Effectiveness Training Program. The central aim of the
      intervention was to improve the ability of caregivers to cope with the stressful
      demands at the core of caring for a demented person, rather than to focus on
      information and the task-oriented aspects of caring. The two components of the
      intervention deal with the cognitive appraisal of stressors and coping
      strategies, with a view to determining which strategies are most appropriate on
      the basis of the changeability of stressors. Three coping strategies were
      proposed: problem solving (problem-focused coping to deal with changeable
      stressors), reframing (emotion-focused coping to manage the emotional response to
      unchangeable stressors), and seeking social support (problem- or emotion-focused
      coping). The most salient characteristics of this group intervention were its
      intensity (15 meetings) and its focus on the caregivers' daily reality, which
      provided concrete reference points for the discussion of conceptual notions.

PMID- 12217093
TI  - Working with older people with communication difficulties: an evaluation of care
      worker training.
AB  - Studies suggest that a high proportion of older people in residential and nursing
      care have communication difficulties and there is some awareness of the need for
      staff training to allow effective communication to be achieved. This paper
      describes part of the evaluation of a one-day training package aimed at enabling
      care staff to communicate with older people who have a variety of communication
      difficulties. Care staff from four partner agencies completed questionnaires pre-
      and post-training, addressing contact with people with communication disorders,
      previous training on communication, knowledge about communication, attitudes
      towards communication problems and strategies to help communication with people
      who have communication difficulties. Positive gains were found in attitudes and
      self-perceptions of knowledge and competence, as well as in appropriate citations
      of strategies to enhance communication. The findings are discussed with reference
      to the need for enhanced communication skills in care workers engendered by
      current developments in care policy.

PMID- 12217094
TI  - Formal and informal care for people with dementia: factors associated with
      service receipt.
AB  - Details of service receipt by 132 people diagnosed with dementia and their carers
      were collected in South London (boroughs of Lewisham, Camberwell, Southwark and
      Croydon), a geographical area served by several health and social care providers.
      The data collected included the Caregiver Activity Survey, which details the
      informal care given. This paper reports the formal and informal services received
      by the people with dementia at entry to the study. The amount of time spent on
      specific caring tasks by all informal carers of people with dementia averaged
      seven hours per week, but was significantly higher for co-resident carers, even
      when controlling for the level of dependency of the person cared-for. The odds
      ratios of receipt of formal services are given, according to where people were
      living: in the community or residential care, with co-resident carers or alone.

PMID- 12217095
TI  - Is it contagious? Affect similarity among spouses.
AB  - Theories of emotional contagion suggest that spouses mutually experience
      affective or emotional states. However, empirical support for this theory is
      limited. Using a dyadic approach, this study examines affect similarity of
      depressive symptoms between elders with vision impairment and their spouses. As
      part of an investigation on older couples dealing with disability, 123 elders
      dealing with a recent vision loss and their spouses were interviewed. Guided by a
      stress process model, predictors of spouse depressive symptoms were examined.
      Hierarchical regression analyses revealed that the spouse's race, health, care
      giving appraisal, self-efficacy, conflict with other family members regarding
      their partner, and their partner's depressive symptoms significantly predicted
      spouse depression. Specifically, spouses who were white, in poorer health,
      experienced more care-giving burden, had more family conflict, and poorer self
      efficacy, were more likely to be depressed. Entered in the final step, elder
      depression uniquely contributed to the prediction of spouse depression. This
      points to affect similarity among spouses, which suggests that when one spouse is
      depressed, the other spouse is likely to experience a similar depressive
      symptomatology.

PMID- 12217096
TI  - Cognitive coping and depressive symptoms in the elderly: a longitudinal study.
AB  - The objective of the present longitudinal study was to examine the relationship
      between cognitive coping strategies and depressive symptoms at old age. At the
      two and a half year follow-up study, a community sample of 99 people aged 67
      years and older filled out a self-report questionnaire comprising the Geriatric
      Depression Scale, the Cognitive Emotion Regulation Questionnaire and a negative
      life events checklist. Cognitive coping strategies seemed to play an important
      role in relation to depressive symptoms in late life. Elderly persons with more
      depressive symptoms reported to use acceptance, rumination and catastrophizing to
      a significantly higher extent and positive reappraisal to a significantly lower
      extent than those with lower depression scores. After controlling for negative
      life events and prior depressive symptoms, acceptance and positive reappraisal
      retained their significant relationship with current depressive symptoms. It is
      suggested that intervention programs should pay attention to these aspects by
      challenging the 'maladaptive' strategies, and by supplying the more 'adaptive'
      strategies. This could be linked to the well-established cognitive therapies.

PMID- 12217097
TI  - The prognosis of depression in old age: outcome six to eight years after clinical
      treatment.
AB  - Previous studies suggest that the short-term outcome in severely depressed
      elderly in The Netherlands is worse compared to other studies in the Western
      world. The present study examines the long-term prognosis of hospitalized elderly
      patients with major depressive disorder and possible predictors of outcome. One
      hundred and five elderly inpatients with unipolar major depression, admitted by
      regional mental health services in a geographically delimited area, were
      evaluated six to eight years after index episode by trained residents using a
      structured diagnostic interview (C.I.D.I.) The GP was interviewed using a
      standard questionnaire. At follow-up 40% of the original sample had died. Of the
      survivors 33% had fared well, 24% had a relapsing course, 22% had residual
      symptoms, 11% were continuously ill, and 9% had probable dementia. With respect
      to prognostic factors, personality disorder predicted a worse outcome. All
      patients with a major depressive disorder at follow-up received specialised care
      and used antidepressants. None of the patients received ECT. The mortality rate
      in clinically treated elderly with major depressive disorder is high. Among
      survivors the long-term prognosis in The Netherlands is comparable with other
      studies to date. The presence of a personality disorder predicts worse outcome.
      Though the accessibility of services seems to be good, more vigorous treatment
      was not applied.

PMID- 12217098
TI  - Placements in psychiatric institutions, nursing homes, and homes for the elderly
      by Belgian general practitioners.
AB  - This research is an epidemiological study of long-term care facility admissions
      to various types of institutions (homes for the elderly, nursing homes,
      psychiatric institutions) during 1994 in Belgium. Data were obtained from a
      network of 143 general practitioners, which acts as a reliable surveillance
      system for health-related data. For every patient who was institutionalized,
      physicians were asked to record the following information: (1) type of
      institution in which the patient was placed; (2) medical conditions; (3) current
      living situation; (4) reason for institutionalization; (5) length of the waiting
      time for institutionalization, and (6) whether or not the patient was
      hospitalized prior to the institutionalization. The overall incidence for
      institutionalization among older patients was 1%. The most common medical
      conditions upon placement were functional impairments and dementia. Over half the
      patients lived alone just prior to the placement and family members made the
      majority of requests for placements. Compared to placements in other types of
      institutions, those to psychiatric facilities were more likely to be 'urgent' and
      waiting times for admission to these institutions were shorter. Over half of all
      placements were preceded by an admission to a medical hospital. Few placements
      (16%) were made with the consultation of home care services. Finally, in about
      two thirds of the cases, patients were cared for by their general practitioner
      while they were institutionalized.

PMID- 12217099
TI  - Decline in verbal memory performance with advancing age: the role of frontal lobe
      functioning.
AB  - This study investigated the relationship between measures of frontal lobe
      functioning (FLF) and verbal memory performance among healthy, community-dwelling
      older adults (60-85 years old). All were administered measures of FLF, attention,
      verbal memory, and depression. After controlling for the effects of attention and
      depression, FLF accounted for significant amounts of the variance in verbal
      memory scores. Age related to the FLF measure according to the level of
      organization of verbal material to be recalled. Frontal lobe functioning and
      performance on an attention measure explained the greatest amount of the variance
      in the recall of unorganized verbal material, whereas age and attention abilities
      were the best predictors of the recall of organized verbal material. The data
      indicate a central role of frontal dysfunction in understanding age-related
      memory loss.

PMID- 12217100
TI  - The Acute versus Chronic Pain Questionnaire (ACPQ) and actual pain experience in
      older people.
AB  - The Acute versus Chronic Pain Questionnaire (ACPQ) was applied to older people.
      Two groups emerged from an analysis of which an item of each pair (an acute and a
      chronic affective item) was considered to cause the most suffering. One group of
      subjects comprised those who expected to suffer more from one or more acute pain
      items (high-ACPQ group, n = 35). A second group emerged for whom none of the
      acute items was considered to be a burden (low-ACPQ group, n = 33). It was
      hypothesized that, compared to the low-ACPQ group, the subjects with high-ACPQ
      scores selected acute ACPQ-items due to a decline in the experience of chronic
      affective pain. This hypothesis predicted lower scores on the chronic ACPQ-items
      and lower scores on scales evaluating the subjects' own chronic affective pain.
      The results showed that, irrespective of the group, the chronic ACPQ-items were
      considered to produce the most burdens. However, compared with the low-ACPQ
      group, the high-ACPQ group reported experiencing significantly more pain from the
      acute ACPQ-items. Moreover, the latter group indicated suffering less pain from
      their own chronic pain conditions. The present findings suggest that the
      selection of one or more acute items of the ACPQ (high-ACPQ group) may point to
      an alteration in subjects' actual pain experience.

PMID- 12217101
TI  - Research into telehealth applications in speech-language pathology.
AB  - A literature review was conducted to investigate the extent to which telehealth
      has been researched within the domain of speech-language pathology and the
      outcomes of this research. A total of 13 studies were identified. Three early
      studies demonstrated that telehealth was feasible, although there was no
      discussion of the cost-effectiveness of this process in terms of patient
      outcomes. The majority of the subsequent studies indicated positive or
      encouraging outcomes resulting from telehealth. However, there were a number of
      shortcomings in the research, including a lack of cost benefit information,
      failure to evaluate the technology itself, an absence of studies of the
      educational and informational aspects of telehealth in relation to speech
      language pathology, and the use of telehealth in a limited range of communication
      disorders. Future research into the application of telehealth to speech-language
      pathology services must adopt a scientific approach, and have a well defined
      development and evaluation framework that addresses the effectiveness of the
      technique, patient outcomes and satisfaction, and the cost benefit relationship.

PMID- 12217102
TI  - A systematic review of the efficacy of telemedicine for making diagnostic and
      management decisions.
AB  - We conducted a systematic review of the literature to evaluate the efficacy of
      telemedicine for making diagnostic and management decisions in three classes of
      application: office/hospital-based, store-and-forward, and home-based
      telemedicine. We searched the MEDLINE, EMBASE, CINAHL and HealthSTAR databases
      and printed resources, and interviewed investigators in the field. We excluded
      studies where the service did not historically require face-to-face encounters
      (e.g. radiology or pathology diagnosis). A total of 58 articles met the inclusion
      criteria. The articles were summarized and graded for the quality and direction
      of the evidence. There were very few high-quality studies. The strongest evidence
      for the efficacy of telemedicine for diagnostic and management decisions came
      from the specialties of psychiatry and dermatology. There was also reasonable
      evidence that general medical history and physical examinations performed via
      telemedicine had relatively good sensitivity and specificity. Other specialties
      in which some evidence for efficacy existed were cardiology and certain areas of
      ophthalmology. Despite the widespread use of telemedicine in most major medical
      specialties, there is strong evidence in only a few of them that the diagnostic
      and management decisions provided by telemedicine are comparable to face-to-face
      care.

PMID- 12217103
TI  - Evaluation of videoconferenced grand rounds.
AB  - We evaluated various aspects of grand rounds videoconferenced from a tertiary
      care hospital to a regional hospital in Nova Scotia. During a five-month study
      period, 29 rounds were broadcast (19 in medicine and 10 in cardiology). The total
      recorded attendance at the remote site was 103, comprising 70 specialists, nine
      family physicians and 24 other health-care professionals. We received 55
      evaluations, a response rate of 53%. On a five-point Likert scale (on which
      higher scores indicated better quality), mean ratings by remote-site participants
      of the technical quality of the videoconference were 3.0-3.5, with the lowest
      ratings being for ability to hear the discussion (3.0) and to see visual aids
      (3.1). Mean ratings for content, presentation, discussion and educational value
      were 3.8 or higher. Of the 49 physicians who presented the rounds, we received
      evaluations from 41, a response rate of 84%. The presenters rated all aspects of
      the videoconference and interaction with remote sites at 3.8 or lower. The lowest
      ratings were for ability to see the remote sites (3.0) and the usefulness of the
      discussion (3.4). We received 278 evaluations from participants at the presenting
      site, an estimated response rate of about 55%. The results indicated no adverse
      opinions of the effect of videoconferencing (mean scores 3.1-3.3). The estimated
      costs of videoconferencing one grand round to one site and four sites were C
      dollars 723 and C dollars 1515, respectively. The study confirmed that
      videoconferenced rounds can provide satisfactory continuing medical education to
      community specialists, which is an especially important consideration as
      maintenance of certification becomes mandatory.

PMID- 12217104
TI  - Client satisfaction in a feasibility study comparing face-to-face interviews with
      telepsychiatry.
AB  - We carried out a pilot study comparing satisfaction levels between psychiatric
      patients seen face to face (FTF) and those seen via videoconference. Patients who
      consented were randomly assigned to one of two groups. One group received
      services in person (FTF from the visiting psychiatrist) while the other was seen
      using videoconferencing at 128 kbit/s. One psychiatrist provided all the FTF and
      videoconferencing assessment and follow-up visits. A total of 24 subjects were
      recruited. Three of the subjects (13%) did not attend their appointments and two
      subjects in each group were lost to follow-up. Thus there were nine in the FTF
      group and eight in the videoconferencing group. The two groups were similar in
      most respects. Patient satisfaction with the services was assessed using the
      Client Satisfaction Questionnaire (CSQ-8), completed four months after the
      initial consultation. The mean scores were 25.3 in the FTF group and 21.6 in the
      videoconferencing group. Although there was a trend in favour of the FTF service,
      the difference was not significant. Patient satisfaction is only one component of
      evaluation. The efficacy of telepsychiatry must also be measured relative to that
      of conventional, FTF care before policy makers can decide how extensively
      telepsychiatry should be implemented.

PMID- 12217105
TI  - An eight-year study of internet-based remote medical counselling.
AB  - We carried out a prospective study of an Internet-based remote counselling
      service. A total of 15456 Internet users visited the Website over eight years.
      From these, 1500 users were randomly selected for analysis. Medical counselling
      had been granted to 901 of the people requesting it (60%). One hundred and sixty
      four physicians formed project groups to process the requests and responded using
      email. The distribution of patients using the service was similar to the
      availability of the Internet: 78% were from the European Union, North America and
      Australia. Sixty-seven per cent of the patients lived in urban areas and the
      remainder were residents of remote rural areas with limited local medical
      coverage. Sixty-five per cent of the requests were about problems of internal
      medicine and 30% of the requests concerned surgical issues. The remaining 5% of
      the patients sought information about recent developments, such molecular
      medicine or aviation medicine. During the project, our portal became inaccessible
      five times, and counselling was not possible on 44 days. There was no hacking of
      the Website. Internet-based medical counselling is a helpful addition to
      conventional practice.

PMID- 12217106
TI  - Social presence in telemedicine.
AB  - We studied consultations between a doctor, emergency nurse practitioners (ENPs)
      and their patients in a minor accident and treatment service (MATS). In the
      conventional consultations, all three people were located at the main hospital.
      In the teleconsultations, the doctor was located in a hospital 6 km away from the
      MATS and used a videoconferencing link connected at 384 kbit/s. There were 30
      patients in the conventional group and 30 in the telemedical group. The
      presenting problems were similar in the two groups. The mean duration of
      teleconsultations was 951 s and the mean duration of face-to-face consultations
      was 247 s. In doctor-nurse communication there was a higher rate of turn taking
      in teleconsultations than in face-to-face consultations; there were also more
      interruptions, more words and more 'backchannels' (e.g. 'mhm', 'uh-huh') per
      teleconsultation. In doctor-patient communication there was a higher rate of turn
      taking, more words, more interruptions and more backchannels per
      teleconsultation. In patient-nurse communication there was relatively little
      difference between the two modes of consulting the doctor. Telemedicine appeared
      to empower the patient to ask more questions of the doctor. It also seemed that
      the doctor took greater care in a teleconsultation to achieve coordination of
      beliefs with the patient than in a face-to-face consultation.

PMID- 12217107
TI  - Assessment of prehospital chest pain using telecardiology.
AB  - Two hundred general practitioners were equipped with a portable
      electrocardiograph which could transmit a 12-lead electrocardiogram (ECG) via a
      telephone line. A cardiologist was available 24 h a day for an interactive
      teleconsultation. In a 13-month period there were 5073 calls to the
      telecardiology service and 952 subjects with chest pain were identified. The
      telecardiology service allowed the general practitioners to manage 700 cases
      (74%) themselves; further diagnostic tests were requested for 162 patients (17%)
      and 83 patients (9%) were sent to the hospital emergency department. In the last
      group a cardiological diagnosis was confirmed in 60 patients and refuted in 23.
      Seven patients in whom the telecardiology service failed to detect a cardiac
      problem were hospitalized in the subsequent 48 h. The telecardiology service
      showed a sensitivity of 97.4%, a specificity of 89.5% and a diagnostic accuracy
      of 86.9% for chest pain. Telemedicine could be a useful tool in the diagnosis of
      chest pain in primary care.

PMID- 12217108
TI  - Hand-held digital video-camera for eye examination and follow-up.
AB  - We developed a hand-held digital colour video-camera for eye examination in
      primary care. The device weighed 550 g. It featured a charge-coupled device (CCD)
      and corrective optics. Both colour video and digital still images could be taken.
      The video-camera was connected to a PC with software for database storage, image
      processing and telecommunication. We studied 88 normal subjects (38 male, 50
      female), aged 7-62 years. It was not necessary to use mydriatic eye drops for
      pupillary dilation. Satisfactory digital images of the whole face and the
      anterior eye were obtained. The optic disc and the central part of the ocular
      fundus could also be recorded. Image quality of the face and the anterior eye
      were excellent; image quality of the optic disc and macula were good enough for
      tele-ophthalmology. Further studies are needed to evaluate the usefulness of the
      equipment in different clinical conditions.

PMID- 12217109
TI  - Telemedicine in the management of a cervical dislocation by a mobile
      neurosurgeon.

PMID- 12217111
TI  - A scientific approach to the assessment of telemedicine acceptance.

PMID- 12217110
TI  - Teledentistry using videoconferencing and a DICOM image management system.

PMID- 12217112
TI  - Telemedicine and changes in the distribution of tasks between levels of care.
AB  - The present investigation, which was part of a larger study, was designed to
      answer the question 'Has telemedicine produced changes in the distribution of
      tasks between the general practitioner and specialist, or between the local
      hospital and university/central hospital?' Qualitative interviews were carried
      out with 30 persons involved in four telemedicine services in Norway:
      teledermatology, tele-otolaryngology, telepsychiatry, and a telepathology frozen
      section service. The results indicated that telemedicine does not produce large
      changes in the distribution of tasks. The reported effects were largest and most
      complex for telepsychiatry, followed by teledermatology. Local variations in how
      telemedicine is practised may explain the variation in the findings between
      telemedicine applications.

PMID- 12217113
TI  - Virtual multidisciplinary teams for cancer care.
AB  - A recent report on cancer services in Wales recommended an integrated cancer
      service. The proposed model was difficult to introduce in rural areas, where
      health-care sites and staff are far apart. Videoconferencing equipment was
      installed in the Singleton Hospital, Swansea, and the Bronglais General Hospital,
      Aberystwyth, 120 km away. During the first year, 42 videoconferencing
      multidisciplinary team meetings were held using ISDN at 384 kbit/s. A total of
      202 cases were reviewed. The cancers were colorectal, breast and lung. There was
      only one aborted session, which was due to an ISDN line fault. The average
      attendance at the meetings was 15 staff, of whom eight were essential team
      members. Regular multidisciplinary team meetings reduced the need for patients to
      travel. They also increased access to expert opinion and reduced the delay in
      implementing treatment.

PMID- 12217114
TI  - Evaluation of a pilot telemedicine network for accident and emergency work.
AB  - A pilot accident and emergency teleconsulting service was established in
      Scotland. It was based at the accident and emergency department of the main
      hospital in Aberdeen. There were three peripheral sites in rural Grampian
      (Peterhead, Turriff and Huntly) and one in the Shetland Isles. The
      videoconferencing equipment used was connected by ISDN at 384 kbit/s. During the
      15 months of the study, 1998 videoconference calls were made, of which 402 (20%)
      calls were made to the accident and emergency department for clinical
      consultations. The majority of the clinical calls (95%) were made between 09:00
      and 17:00, and more than 90% were completed within 20 min. During the majority of
      calls (87%) one or more X-ray images were transmitted. The majority of patients
      (89%) received treatment without transportation to the main centre in Aberdeen.
      The present study demonstrated that accident and emergency teleconsultations can
      be technically reliable, effective in reducing the number of patient transfers
      and acceptable to the referring clinicians. As a result, approximately  1.5
      million has been made available by the government to develop a national system
      for Scotland.

PMID- 12217115
TI  - Patient satisfaction with telemedical access to specialty services in rural
      California.
AB  - We assessed patient satisfaction with the use of telemedicine in rural
      California, in comparison with usual face-to-face care. A standardized patient
      satisfaction questionnaire was developed using a five-point scale to measure
      dimensions of care in a telemedicine environment. Twenty-four primary care sites
      in 18 Californian counties submitted satisfaction data. The patient response rate
      was 61% (n = 793). Consultations were provided in 27 specialties. The responses
      to the questionnaires indicated that telemedicine made it easier for patients to
      receive specialty care (91% of patients satisfied, mean score 4.6). There was
      general satisfaction with telemedicine (87%, mean 4.5), a willingness to continue
      receiving services (90%, mean 4.6) and most patients felt that they would not
      receive better care in person (61%, mean 2.3). Patients stated that they received
      the necessary information from specialists (85%, mean 4.5) and had their
      questions answered by a primary care provider or nurse (89%, mean 4.7). Seven
      hundred and forty-one patients submitted travel information. There was an average
      decrease in travel distance of 170 km and time savings of 130 min using
      telemedicine. The average cost of travel to a specialty appointment was $83 (n =
      310). The present study suggests that telemedicine is acceptable to patients as a
      method of improving access to specialty expertise, and compares favourably with
      face-to-face care.

PMID- 12217116
TI  - Child advocacy outreach: using telehealth to expand child sexual abuse services
      in rural Kentucky.
AB  - We evaluated the use of videoconferencing as an educational and consultative tool
      for physicians and mental health staff providing services for child victims of
      sexual abuse in rural Kentucky. The number of counties with access to sexual
      abuse examinations by a qualified physician increased from 16 to 23 in the first
      year and to 54 in the second. The number of cases increased from 77 to 83 in the
      first year and to 339 in the second year. The number of consultations increased
      from zero to eight in the first year and to 74 in the second year. A user survey
      showed that the equipment supported clinical decision making, was useful and was
      easy to use. However, it was not as effective for case conferencing as for one-to
      one interactions. Rural health professionals knowledge of child sexual abuse
      increased.

PMID- 12217117
TI  - Integration of telemedicine into emergency medical services.
AB  - We developed an integrated model of telemedicine services in emergency medical
      care. The architecture was designed to support pre-hospital management. The
      experimental work was carried out with the collaboration of the emergency medical
      services (EMS) in Madrid. Two different study populations were defined: a control
      population using conventional EMS protocols and a population using the
      telemedicine system. The telemedicine system was based on a telepresence service;
      electrocardiograms and images were transmitted from the ambulance to the health
      emergency coordination centre. The cost of dealing with 100 patients using
      telemedicine was C6030 less than the cost of conventional care. The response
      times using telemedicine were significantly lower.

PMID- 12217118
TI  - Development of a website for clinical microbiology in Brazil.
AB  - The quality of Brazilian health services, including clinical microbiology
      laboratories, varies enormously. We established a Website to provide different
      professionals with up-to-date information and to create a virtual Brazilian
      microbiology community. The Website became operational in February 2000 and had
      198,976 hits in the subsequent 20 months. There were 1031 user registrations in
      its virtual community. Different microbiology topics were discussed and three
      virtual training courses (representing about 300 printed pages of information)
      were given. The e-learning centre and the Brazilian virtual community created by
      this Website have facilitated distance learning, and have encouraged professional
      integration within Brazilian clinical microbiology.

PMID- 12217119
TI  - A telemedicine system to support a new model for care of chronically ill
      patients.
AB  - We have developed a new model for the care of chronically ill patients, based on
      home care supported by remote monitoring technology and telemedicine. The
      variables monitored included non-invasive blood pressure, blood oxygen
      saturation, threelead electrocardiogram, spirometry (including flow-volume curve)
      and respiratory rate. The telemedicine system consisted of a home-based patient
      unit and a management centre that received information from the home units. The
      chronic care management centre was installed in two hospitals, in Spain
      (Barcelona) and Belgium (Leuven). We expect this to result in significant cost
      savings and a better quality of care.

PMID- 12217120
TI  - Telemedicine by email--experience in neonatal care at a primary care facility in
      rural India.
AB  - During an 18-month study period, teleconsultations were conducted by email
      between a neonatal intensive care unit at an urban teaching hospital in western
      India and a rural primary care centre 40 km away. There were email consultations
      about 182 newborn babies; these consultations comprised 309 messages sent from
      the primary care centre and 272 messages from the teaching hospital. The average
      reply time was 11.3 h. Thirty-eight babies were referred to the intensive care
      unit at the teaching hospital after these consultations. The remaining 144 babies
      were managed at the primary care centre. Telemedicine helped in the diagnosis,
      referral, treatment and follow-up of patients. The cost of the email service was
      estimated to be Rs12,000 and the savings in avoided transfer were estimated to be
      Rs546,000, a cost-benefit ratio of 1:45.

PMID- 12217121
TI  - Telecolposcopy - a feasibility study in primary care.
AB  - Organized cervical screening has reduced the incidence of invasive cervical
      cancer, but this has resulted in large numbers of women requiring investigation.
      We have investigated the negative predictive value of colposcopy and used
      telemedicine to develop a secondary screening technique for use in primary care.
      A video-colposcope was used to record video-clips, which were subsequently
      transmitted to a specialist for interpretation. The gold standard for the
      comparison was the opinion of the colposcopist who examined the women in the
      hospital colposcopy clinic. Eighty-one out of 97 women were studied by both
      techniques. Using a diagnosis of normal or abnormal, telecolposcopy had a
      sensitivity of 88.9% and a specificity of 93.3%. There was very good agreement
      between the telecolposcopy screener and the colposcopist (Cohen s kappa statistic
      = 0.70). Furthermore, telecolposcopy screening did not grade any cases of
      colposcopic high-grade cervical intraepithelial neoplasia as normal. The pilot
      study has established the validity of diagnosing from transmitted computerized
      video-clips.

PMID- 12217122
TI  - Community coronary units: strategies to promote pre-hospital thrombolysis.
AB  - Early diagnosis and the early delivery of pre-hospital thrombolysis in cases of
      acute myocardial infarction (AMI) have been shown to decrease mortality. Despite
      strong evidence of its benefits, pre-hospital thrombolysis rates are still
      worryingly low. The challenge is to empower community practitioners to deliver
      thrombolysis. In the Grampian region there is a network of community hospitals
      which have been equipped with both videoconferencing and remote telemetry
      equipment. This allows realtime consultation with the local accident and
      emergency department and coronary care unit. Early trials of the system show that
      clinical information can be viewed in realtime, with transfer of a 12-lead
      electrocardiogram at 60 s intervals. This will give general practitioners
      unprecedented access to specialist advice. Our aim is to use a combination of
      teaching and decision support technology to ensure that all patients with AMI
      have the opportunity to access timely and appropriate prehospital thrombolysis.

PMID- 12217123
TI  - Air sea rescue, telemedicine style.
AB  - Historically, requests from shipping in UK coastal waters for emergency medical
      advice have been handled on an ad hoc basis by various accident and emergency
      departments on behalf of the Coastguard. A formal contract to provide this
      service has recently been established with the Aberdeen Royal Infirmary in
      Scotland and the Royal Alexandra Hospital in Portsmouth, England. A pre-contract
      audit showed that the involvement of medical professionals in the evacuation
      decision improved the quality of triage and intervention. The medical staff at
      both hospitals received training in giving medical advice and the level of
      medical knowledge that could reasonably be expected of ships crews. Providing
      advice to commercial airlines developed from the maritime service. In association
      with a private company, staff at the Aberdeen Royal Infirmary have developed
      procedures to support cabin crew and medical professionals on board (initial
      figures suggest that a medical professional is present on about 45% of flights).
      At present, although there are insufficient data to draw any firm conclusions, it
      appears that up to two-thirds of diversions could be avoided using this service.

PMID- 12217124
TI  - An evaluation of the use of and user satisfaction with a teleconsultation system
      in oncology practice.
AB  - A three-year oncology teleconsulting project was concluded in November 2000.
      During a six-month study period, 38 clinical physicians and 47 nurses used the
      system. A total of 617 electronic patient records were created in the oncology
      department, 297 in dermatology and 24 in gynaecology. There were 45 synchronous
      teleconsultations involving various participants, lasting a total of 708 min. We
      conducted surveys of the attitudes of users to the teleconsulting system both
      before and after its implementation. There were no significant differences
      between the two surveys and the results showed that users had a positive reaction
      to the system and high expectations of its future utilization.

PMID- 12217125
TI  - Telemedicine applications for the regional paediatric cardiology service in
      Northern Ireland.
AB  - The regional paediatric cardiology centre in Northern Ireland has a telemedicine
      network linking the neonatal units of three district general hospitals using ISDN
      and IP-compliant equipment. We have previously reported the use of ISDN
      transmission at 128 kbit/s for remote echocardiography. In a series of 61
      patients, a total of 59 transmitted scans were of sufficient diagnostic quality
      to confirm or exclude the presence of major congenital heart disease (CHD). There
      were three diagnostic errors (7%). Subsequently, we have examined the use of ISDN
      transmission at 384 kbit/s. Echocardiographic studies were carried out on 21
      patients and all were followed up. Fourteen patients (67%) had CHD confirmed.
      There were two diagnostic errors (10%). Our experience of transmitting live
      echocardiographic images suggests that ISDN at 384 kbit/s provides the optimum
      balance between the clarity of the transmitted images and costs. We expect that
      IP videoconferencing will offer similar quality but at a lower running cost, and
      are currently assessing it in a pilot study. All sites within our network will
      remain capable of ISDN transmission until the efficacy and reliability of IP
      transmission has been demonstrated in a controlled trial. The clinical
      telemedicine service has led to the earlier diagnosis of and instigation of
      appropriate treatment for CHD.

PMID- 12217126
TI  - Developing a protocol for the use of telenursing in community health in
      Australia.
AB  - As the first step in developing a protocol for the use of video-phones in
      community health, we carried out a feasibility study among clients with a range
      of health needs. Clients were equipped with a commercially available video-phone
      connected using the client s home telephone line. A hands-free speaker-phone and
      a miniature video-camera (for close-up views) were connected to the video-phone.
      Ten clients participated: five required wound care, two palliative care, two long
      term therapy monitoring and one was a rural client. All but two were aged 75
      years or more. Each client had a video-phone for an average of two to three
      weeks. During the six months of the study, 43 client calls were made, of which 36
      (84%) were converted to video-calls. The speaker-phone was used on 24 occasions
      (56%) and the close-up camera on 23 occasions (53%). Both clients and nurses
      rated the equipment as satisfactory or better in questionnaires. None of the
      nurses felt that the equipment was difficult to use, including unpacking it and
      setting it up; only one client found it difficult. Taking into account the
      clients responses, including their free-text comments, a judgement was made as to
      whether the video-phone had been useful to their nursing care. In seven cases it
      was felt to be unhelpful and in three cases it was judged helpful. Although the
      study sample was small, the results suggest that home telenursing is likely to be
      useful for rural clients in Australia, unsurprisingly, because of the distances
      involved.

PMID- 12217127
TI  - The use of videoconferencing to enhance tertiary mental health service provision
      to the island of Jersey.
AB  - A six-month trial of videoconferencing was undertaken between the States of
      Jersey Health and Social Services in the Channel Islands and the South London and
      Maudsley NHS Trust in England. The purpose of the project was to evaluate the
      effectiveness and benefits of obtaining specialist tertiary mental health
      services not normally available on the island of Jersey. During the six-month
      pilot project in 2001, five teleconsultations were conducted: two acute
      psychiatric assessments and three case reviews. In addition, six presentations
      using videoconferencing were held on forensic psychiatry (24 participants),
      affective disorders (12), psychosis (8), eating disorders (3), crisis disorders
      (12) and community specialist teams (12). Results using the Guy s Communication
      Questionnaire indicated high satisfaction levels from all participants. The
      project successfully raised the awareness of telemedicine and its potential in
      the delivery of mental health services in Jersey.

PMID- 12217128
TI  - Implementation of telemedicine: the problem of evaluation.
AB  - In the UK, few telemedicine applications have endured beyond the trial phase. It
      is commonly said that lack of evidence is responsible for the lack of
      implementation. This assumes that evidence will lead to implementation. Studies
      show that this is naive, especially in organizations like health-care systems,
      which are characterized by professional dominance. Furthermore, other research
      indicates that the nature of the changes experienced by clinicians in
      telemedicine experiments is sometimes limiting compared with conventional
      practice. This presents a dilemma for evaluation since it cannot reliably take
      place until a particular technique has become stable and accepted into the daily
      routine. A programme of selected case studies is recommended to develop knowledge
      of how telemedicine can become a taken-for-granted part of medical care.

PMID- 12217129
TI  - PaSent--the patient's personal health adviser.
AB  - We have attempted to automate the search for medical information that is relevant
      to a patient s electronic record. We used anonymous medical reports sent from the
      University Hospital of Tromso to general practitioners as input data. The medical
      reports were matched against the NEL, a Web-based medical dictionary and document
      collection service for general practitioners. We evaluated only the three top
      scoring documents automatically selected by the system. A medical professional
      evaluated whether a selected document from the NEL was very relevant to the
      contents of the input report, relevant or irrelevant. Initial tests showed that
      60% of the top three selected documents found by the PaSent system were very
      relevant or relevant to the contents of the medical report used as input data.
      Our preliminary conclusion is that automatic location of relevant information is
      possible using medical reports as input data.

PMID- 12217130
TI  - Patient-focused urban tele-ophthalmology services.
AB  - Since 2000, routine tele-ophthalmology services have been provided by St Erik's
      Eye Hospital to three large urban primary care centres in Stockholm. Diagnostic
      support from the specialist eye hospital to primary care centres uses video slit
      lamps and realtime videoconferencing. After the initial introduction period at
      the primary care centres, the number of teleconsultations stabilized at a very
      low level. Despite this, the general practitioners learned to handle more
      diagnostic conditions by themselves and to identify what diagnostic situations
      should be referred to a specialist without having to consult the specialist
      beforehand via telemedicine. The availability of instant eye expertise via
      telemedicine therefore proved to be an excellent on-the-job training tool to
      develop and maintain the diagnostic competence of general practitioners. Patient
      satisfaction was high.

PMID- 12217131
TI  - A remote auscultation tool for advanced home health-care.
AB  - We have developed an Internet-based tool for remote realtime auscultation. The
      device was based on a commercially available electronic stethoscope and a PC
      which digitized and transmitted the signals. A voice and video channel were also
      available. The remote auscultation tool was evaluated between two sites in Sweden
      separated by a distance of 500 km. A doctor at one of the sites performed cardiac
      and pulmonary auscultations on patients located at the other site. Four test
      patients were assisted by a nurse operating the electronic stethoscope. The
      auscultation sessions were performed with and without video support to assess the
      importance of visual contact between doctor and patient. Twenty sessions were
      conducted (excluding technical testing to solve problems with the equipment).
      Audio quality was sufficient, as judged subjectively by the doctors concerned.
      Video support improved the doctor s confidence that the stethoscope was being
      operated properly and greatly simplified the interaction. Moreover, it improved
      all participants subjective impression of the virtual meeting. Our work
      demonstrates the feasibility of performing remote auscultation sessions over the
      Internet.

PMID- 12217132
TI  - A needs assessment of the potential users of a South Pacific telehealth service.
AB  - Qualitative methods such as focus groups, individual interviews, case studies and
      participant observation were used to complete a needs assessment for a telehealth
      service in the South Pacific. Participants from the Cook Islands and Fiji were
      able to identify extensive uses for a telehealth service, but also identified
      barriers to its implementation. These included the extremely limited
      telecommunications and electrical infrastructure found in South Pacific
      countries, the high cost of Internet access and staffing shortages. The effective
      implementation of a telehealth site will probably require the use of clinician
      drivers with an interest in telehealth to encourage colleagues less enthusiastic
      to change their work practices. Telehealth in the South Pacific would improve
      services across a wide geographical area, but initial and continuing costs would
      be high due to the lack of infrastructure.

PMID- 12217133
TI  - A system for teleconsulting, communication and distance learning for people with
      disabilities.
AB  - Telemedicine and telelearning applications should greatly improve the quality of
      life of all patients but especially those with a disability. However, people with
      severe physical disabilities are often unable to benefit from them because they
      cannot use the man-machine interfaces of most telecommunication equipment. We
      have therefore constructed a system that allows access to three methods of
      communication: text files, email messages and SMS messages. The user interacts
      using a switchtype interface. The system consists of a PC with a networking
      adapter, a switch interface adapter and special software. The main advantages of
      the system are the possibility of using rapid communication (email, SMS mobile
      phone messages) for teleconsulting and emergencies, and participation in distance
      learning.

PMID- 12217134
TI  - Development and use of online mental health services in Greece.
AB  - E-mental health refers to the use of telecommunication and information technology
      in mental health services. In Greece, ordinary telephone communications have been
      used to provide mental health services, such as a psychiatric crisis intervention
      line (METB). E-psychiatry is a relatively new approach to delivering psychiatric
      services through the Internet. We have developed an e-psychiatry Website,
      Glaucopis-net. The main objective is to provide information on a broad range of
      psychiatric conditions, such as dementia, depression and anxiety. Email mental
      health services will be offered as an alternative way of accessing help.
      Confidentiality issues concerning patient records and personal data will be
      treated in accordance with Greek legislation. Glaucopis-net will integrate new
      telecommunication and information services with classical mental health services.

PMID- 12217135
TI  - Future patient care: tele-empowerment.
AB  - We explored the attitudes and responses of older people to telecare and home
      based technologies. The perceptions of a small group of subjects who had no
      knowledge or experience of the use of telehealth equipment were compared with the
      experiences of a second small group who had used a video-link in a remote
      consultation with their general practitioner. Data were collected by engaging
      subjects in a semistructured interview in their own home. A questionnaire, which
      was developed following the analysis of the interview data, was also distributed
      to three client groups in Scotland. These groups were day hospital patients,
      residents of local authority sheltered housing schemes and residents of a private
      housing association. One hundred and ninety-nine questionnaires were returned (a
      42% response rate), all from people aged 60 years and over. Analysis of the
      questionnaires suggested that the main demographic factors associated with
      positive attitudes to telecare were age, home ownership, dwelling type (sheltered
      housing or not) and household composition. The results suggest that an
      appropriate nurse-led telehealth service, which facilitates trust between
      clients, providers and the technology, could be the mechanism by which to
      encourage people to accept and use home-based systems.

PMID- 12217136
TI  - Cost-benefit analysis of a new health insurance card and electronic prescription
      in Germany.
AB  - A new (electronic) health insurance card for Germans could eliminate errors in
      documenting exemption from charges. Electronic prescribing, if introduced
      nationally, would lead to improved medication-related information and the
      availability of structural and control data. An analytical model for Germany has
      shown that DM1 billion would be saved from improved prescription information
      simply in terms of the number of avoided hospital stays now paid for by the
      health-care system. However, the distribution of costs and benefits among the
      participants in health-care would be very uneven. For example, doctors would have
      the largest investment and operating costs, but would enjoy only marginal savings
      (less than 2% of investment).

PMID- 12217137
TI  - The benefits of a qualitative approach to telemedicine research.
AB  - We used qualitative research to evaluate the experience of the participants in
      teleconsultations between primary and secondary care. Semistructured interviews
      were conducted with 15 hospital specialists, 24 general practitioners and 30
      patients. Focus groups were also held with hospital specialists (two groups),
      general practitioners (six groups) and administrative staff (five groups). Sixty
      teleconsultations in six different specialties were video-recorded. Early
      findings show that the participants (hospital specialists, general practitioners
      and patients) had different perceptions of the same teleconsultations.
      Furthermore, the participants perceptions of consultations differed from those of
      the researchers.

PMID- 12217138
TI  - A randomized controlled trial of home telecare.
AB  - We have established a randomized controlled trial of home telecare. The
      intervention aims to address a growing problem in the National Health Service
      (NHS), that is, high admission rates of patients with exacerbations of chronic
      obstructive pulmonary disease (COPD). Equipment procurement for the trial has
      been difficult, as no single supplier was able to meet the project s full
      requirements. The fact that the service is provided by existing clinical NHS
      staff has advantages when considering the generalizability of the results within
      the NHS. However, there are also disadvantages, since existing staff have little
      research experience. Considerable time has been required to help staff
      familiarize themselves with the equipment and become comfortable with its use.
      This has posed a barrier to the implementation of the service.

PMID- 12217139
TI  - Using commercially available technology to assist in the delivery of person
      centred health and social care.
AB  - Videoconferencing (via ISDN at 128 kbit/s) was used between a service provider,
      the South and East Belfast Health and Social Services Trust, and clients at home.
      The equipment was used successfully by various health-care workers and was
      sufficient for the clinical requirements of professional staff. Our experience
      demonstrated that there are clinical benefits of telecare. The users perceived
      that the technology added to the quality of their lives. Clients reported feeling
      less isolated, more secure at home and more in control. The Trust is currently
      commissioning purpose-built accommodation for adults with cognitive impairment.
      The residents will be people who are on the verge of requiring institutional
      care. Presence sensors, appliance and door contacts will allow lifestyle patterns
      to be monitored. The system will notify the service provider's staff of
      variations from the norm for each resident.

PMID- 12217140
TI  - Technical innovations in international e-nursing.
AB  - Saudi Arabia faces a severe shortage of nurses. An online nursing degree is being
      introduced as one approach to this problem. In 1999, the College of Nursing and
      Health Science at George Mason University formed a strategic partnership with
      IMED Link, a private telehealth company, to deliver online nursing education.
      Nine courses have been developed so far, including nursing assessment. The
      educational material will be distributed via Saudi Arabia's telemedicine network.
      The courses will be led by professors of nursing at George Mason University using
      videoconferencing, coupled with online computer classes and Internet tools. Both
      nursing content and expertise in Web technologies are necessary to develop a
      successful e-nursing programme.

PMID- 12217141
TI  - Factors influencing the evaluation of telehealth interventions: preliminary
      results from a qualitative study of evaluation projects in the UK.
AB  - We have carried out a qualitative study of factors that influence the evaluation
      of telehealth. The study concerned six telehealth projects that are being tracked
      over two years. In the first 12 months of the study we carried out semistructured
      interviews and made observations of the participants in the projects. Each case
      study involved 5-15 subjects, many of whom were interviewed several times. The
      results indicate that important issues affecting telehealth evaluation include
      developing and maintaining the technology, reorganization of clinical and
      administrative duties, professional dynamics, and the difficulty of integrating
      service provision and evaluation. The findings suggest that the evaluation of
      telehealth interventions is highly complex, and that this complexity is often
      underestimated in the design and conduct of evaluation studies.

PMID- 12217142
TI  - The north-west region community PACS study.
AB  - A recent study in the West Surrey Health Authority demonstrated substantial
      advantages from viewing a picture archiving and communication system (PACS) as a
      whole-community asset, that is, a community PACS (CPACS). To test how this
      concept could be translated to other situations, the present study extrapolated
      the CPACS concept to the north-west healthcare region of the UK (population
      around seven million). A CPACS is a network covering multiple hospitals and
      community organizations, with a single archive and a broadband network to support
      it. A CPACS would provide a much better service to patients. It would bring
      financial economies of scale of up to 17%. It could provide the big modernization
      idea which brings clinicians, managers and technologists together. On the other
      hand, it could well be too big to manage.

PMID- 12217143
TI  - Can paediatric radiographs be accurately interpreted using an inter-hospital
      telemedicine system?
AB  - Children make up a significant proportion of attendances at accident and
      emergency departments but there is little published information about the use of
      telemedicine for viewing paediatric radiographs in the emergency setting. The
      radiographs and case-notes of 30 children were randomly selected from attendances
      at an accident and emergency department and were then transmitted over a
      telemedicine link equipped with a document camera. The doctor recorded the
      diagnosis and proposed management, along with the confidence in diagnosis and
      satisfaction with the image. This process was repeated using hardcopy radiographs
      and a standard viewing box. Five accident and emergency specialists took part in
      the study; there were in total 300 radiograph viewings. There was one missed
      fracture out of 75 positive radiographs viewed by telemedicine compared with no
      missed fractures on direct inspection of the film. Thirteen radiographs viewed
      over the telemedicine link were thought to be positive or suspicious of injury
      when the formal report was of no bony injury. The sensitivity of fracture
      diagnosis using telemedicine was 98.6% compared with 100% on direct inspection of
      the film, and specificities were 82.6% and 86.6%, respectively. Our study
      suggests that telemedicine can be used to aid diagnosis and make management
      decisions in children with minor trauma.

PMID- 12217144
TI  - An assistive home care environment for people with special needs.
AB  - We have developed a system for supporting people with special needs. It allows
      remote monitoring of electrocardiographic and other signals together with
      multimode environmental control. The multimodal approach allows users with
      disabilities to interact more with the home environment. Telemedicine devices
      were integrated into the system to provide a link to health services. The system
      provided support for the independent living of people with special needs. The
      pilot site was a rehabilitation service attached to the National Paraplegic
      Hospital of Toledo, Spain. During the six-week trial period, the system did not
      fail, nor was any unauthorized access reported. Twelve people with special needs
      and three staff evaluated aspects of the system on a scale from 0 to 9, on which
      higher scores indicated a positive assessment. The mean score for efficiency was
      7.8, for satisfaction 8, for helpfulness 7.4, for controllability 7.2 and for
      learnability 8.

PMID- 12217145
TI  - Establishing a low-cost telemedicine link in far-eastern Russia.
AB  - A community-based primary care partnership was established between the University
      of Kentucky and the Central Hospital in Pereyaslavka, Russia. To assess community
      health needs, a community-initiated decision-making process was employed. As part
      of the primary care partnership, we conducted a telehealth pilot trial between a
      primary care hospital in Pereyaslavka and a tertiary care facility in Khabarovsk.
      Videoconferencing and the transmission of heart and lung sounds via telephone
      lines were successful within the Pereyaslavka Hospital. Videoconferencing was
      successful between the two hospitals (60 km apart) but the telephone lines were
      too noisy for the electronic stethoscopes. Telephone-based videoconferencing may
      prove to be important in helping rural medical practitioners in the Khabarovsk
      Territory to enhance the quality of health-care.

PMID- 12217146
TI  - Telemedicine in the service of peace.
AB  - Ophthalmology is well suited to telemedicine, since optical and imaging devices
      provide the basis for virtually all ophthalmic patient evaluations. We
      established the Middle East Ophthalmology Network among ophthalmologists working
      in 10 major ophthalmology centres in Israel, Jordan, Morocco, the Palestinian
      Authority and Tunisia. The project offered some 50 physicians around the Middle
      East the opportunity to benefit from sharing clinical consultation for diagnosis
      and management decisions beyond physical and political boundaries. In the first
      year, over 100 consultations took place. The system overcame some of the
      constraints imposed by the uneven distribution of medical resources and expertise
      in the region, reduced professional isolation, encouraged more collaboration
      between physicians and offered peace dividends from cooperation between
      physicians across the political divide.

PMID- 12217147
TI  - Video-hypnosis--the provision of specialized therapy via videoconferencing.
AB  - Hypnosis is not normally accessible to patients living in remote areas. We
      conducted a pilot study to evaluate the feasibility of providing hypnosis via
      videoconferencing, using ISDN at 384 kbit/s. Eleven of 15 patients invited to do
      so took part. Ten of the 11 stated that they were satisfied with the video
      hypnosis session and all indicated that they would like to have further video
      hypnosis sessions in the future. Sound quality and image quality were acceptable
      during nearly all sessions, in spite of some interference as a result of
      technical problems and weather conditions. The results suggest that hypnosis can
      be provided successfully via videoconferencing.

PMID- 12217148
TI  - Tele-ultrasound for remote areas.
AB  - Summary We studied the introduction of a telemedicine service for the prenatal
      diagnosis and management of pregnant patients at a remote site in Scotland.
      During a 10-month study period, 85 videoconferences were carried out between the
      remote hospital in Elgin and the fetal medicine unit in Aberdeen. ISDN
      transmission at 384 kbit/s was used. There were technical problems in five calls
      (6%). The mean call duration was 40 min (range 5-60 min). Most calls (62%) were
      for educational reasons and 26% were for clinical purposes. The degree of
      satisfaction recorded by the remote health-care staff was high: the mean score on
      a five-point scale (1, very unsatisfied; 5, very satisfied) for general
      satisfaction with the clinical support was 4.2. The system was found to be both
      clinically useful and educationally beneficial.

PMID- 12217149
TI  - The attitudes, expectations and needs of elderly people in relation to e-health
      applications: results from a European survey.
AB  - We have carried out a survey of elderly people in Europe relating to e-health and
      telemedicine issues. Telephone-based interview techniques were used in 13
      countries and face-to-face interviews were used in Ireland and Portugal, where
      there are significant numbers of houses without telephones. Altogether 9661
      interviews were performed. Most respondents (65%) lived in rural areas or small
      towns; the remainder lived in suburban areas or large towns. Virtually all
      respondents (98%) had access to a television set. About 30% received cable
      television and 13% had access to digital television. Almost half (48%) had access
      to mobile phones (with 42% actually using them), 36% had access to PCs (with 27%
      being active users) and 22% had access to the Internet (with 17% being active
      users). The respondents showed interest in various e-health applications,
      although this declined considerably with age. The survey showed that the older
      people get, the more they depend on medical and social care, and the more they
      tend to live alone, without a family member to look after them. Policy measures
      relating to infrastructure as well as training, education and awareness
      activities will be required to avoid a medical divide between those senior
      citizens who have access to advanced medical advice and services and those who do
      not.

PMID- 12217150
TI  - The accuracy of length and angle measurement in videoconferencing teleradiology.
AB  - Telemedicine was used to make measurements on a series of radiographs. The first
      group consisted of 25 radiographs of the cervical spine; four lengths were
      measured on each. The second group consisted of 100 wrist radiographs showing
      Colles fractures; the degree of backward angulation of the distal fragment was
      measured on each. Measurements were made via a videoconferencing link. The
      consultant used the shared white boarding facility to indicate where on the film
      the measurements were to be made. The videoconferencing link was used to check
      that the measurements were being made correctly and a nurse measured lengths and
      angles. In addition, the consultant used the link to read the scales on the
      measuring instruments for himself. Four different methods of measuring length
      were tested and three methods of measuring angle. A transparent plastic ruler was
      best for measuring length-the emergency nurse practitioner and the consultant
      made almost all measurements to an accuracy of 1 mm. A protractor with pen marker
      was best for measuring angles; all were made to within 2 degrees. Simple methods
      can be used to measure lengths and angles in videoconferencing teleradiology.

PMID- 12217151
TI  - Four years' experience of telemedicine support of a minor accident and treatment
      service.
AB  - In 1996 we studied patients attending a minor accident and treatment service in
      London, some of whom were the subjects of teleconsultations with a main hospital
      emergency department. In the subsequent four years, 56,139 patients were seen at
      the minor accident and treatment service unit. Teleconsultations were performed
      in 2032 cases (3.6%). Most of the teleconsultations (58%) concerned patients with
      fractures. The main reason for teleconsultation was to review and discuss
      radiographs (46%). In comparison with the 1996 study, both the emergency nurse
      practitioners and the consultant had improved the accuracy of their teleradiology
      diagnosis, although the difference was not significant. Most of the telemedicine
      patients (90%) did not need a transfer to the main department. Thus telemedicine
      allowed local decision making in the majority of cases. In the 1996 survey, 75%
      of patients were sent to their general practitioner or to the main hospital
      department; in the present survey, this proportion had halved, to 38%. The
      present study showed that teleconsultations are an effective way of preventing
      patients being transferred unnecessarily from a minor accident and treatment
      service to the main hospital accident and emergency department.

PMID- 12217152
TI  - Theoretical efficiency of a televisiting service for home care support.
AB  - We have made a theoretical study of the potential for televisiting. All journeys
      made by the home care support team in an area of Madrid were reviewed to study
      the possibility of using televisiting. During the year 2000 the team provided an
      average of seven home visits a day. The home visits took 30 min on average, and
      the journey time was 30 min for urban areas and 45 min in the suburbs. We
      estimated that two of each day s visits could be carried out by telemedicine,
      with a mean duration of 15 min each. A model was used to calculate the resource
      demands and the potential cost-savings of televisiting compared with traditional
      home care. Using televisiting, 62% more suburban oncology patients could be
      managed and a cost reduction of euro;6 per visit could be achieved after 10
      weeks.

PMID- 12217153
TI  - A telemedicine model for integrating point-of-care testing into a distributed
      health-care environment.
AB  - Centralized testing demands costly laboratories, which are inefficient and may
      provide poor services. Recent advances make it feasible to move clinical testing
      nearer to patients and the requesting physicians, thus reducing the time to
      treatment. Internet technologies can be used to create a virtual laboratory
      information system in a distributed health-care environment. This allows clinical
      testing to be transferred to a cooperative scheme of several point-of-care
      testing (POCT) nodes. Two pilot virtual laboratories were established, one in
      Italy (AUSL Modena) and one in Greece (Athens Medical Centre). They were
      constructed on a three-layer model to allow both technical and clinical
      verification. Different POCT devices were connected. The pilot sites produced
      good preliminary results in relation to user acceptance, efficiency, convenience
      and costs. Decentralized laboratories can be expected to become cost-effective.

PMID- 12217154
TI  - Design and performance of a multicentre, randomized controlled trial of
      teleconsulting.
AB  - We have designed and performed a multicentre, randomized controlled trial of
      teleconsulting. The trial investigated the effectiveness and cost implications in
      rural and inner-city settings of using videoconferencing as an alternative to
      general practitioner referral to a hospital specialist. The participating general
      practitioners referred a total of 3170 patients who satisfied the entry criteria.
      Of these, 1040 (33%) failed to provide consent or otherwise refused to
      participate in the trial. Of the patients recruited to the trial, a total of 1902
      (91%) completed and returned the baseline questionnaire. Although the trial was
      successful in recruiting sufficient patients and in obtaining high questionnaire
      response rates, the findings will require careful interpretation to take account
      of the limits which the protocol placed on the ability of general practitioners
      to select patients for referral.

PMID- 12217155
TI  - Design of a centralized telemedicine model in Palestine.
AB  - To provide patients with easy-access telemedicine services in Palestine, a simple
      and low-cost telemedicine system has been established. The system is based on a
      star topology network between local hospitals and a main telemedicine centre. In
      a pilot trial, a computerized tomography image was transmitted from a local
      hospital connected to the telemedicine service centre by ISDN (128 kbit/s). A
      videoconferencing discussion between the two ends was held. The performance of
      the system was satisfactory. The transmission time for a 1 MByte image was about
      60 s. A conference was conducted to discuss this real clinical case by use of
      interactive sharing of the medical record. The session lasted 20 min. Encouraging
      results were obtained. The pilot study suggests that telemedicine can overcome
      existing isolation problems of cities and villages and the difficulties of
      transferring patients from one location to another.

PMID- 12217156
TI  - The North Lewisham telepsychiatry project: beyond the pilot phase.
AB  - The integration of a telepsychiatry application into an inner-city community
      mental health service was evaluated over 10 months. ISDN videoconferencing at 128
      kbit/s was employed for psychiatric consultation between a primary care centre
      and a community mental health centre. A convenience sample of patients and
      referrals seen by videoconferencing was compared with a sample seen face to face.
      During the study period 19 patients were managed by videoconferencing and 12 face
      to face. There were 162 consultations, comprising 81 prearranged
      teleconsultations and 81 prearranged face-to-face consultations. There was no
      significant difference in attendance between videoconferencing and face-to-face
      consultations. Nine of the videoconferencing new referrals had not completed
      their treatment at the end of the study period, compared with only three in the
      face-to-face group. This implies that it takes longer to complete treatment for
      new referrals managed by videoconferencing.

PMID- 12217157
TI  - A comparative study of a new wireless continuous cardiorespiratory monitor for
      the diagnosis and management of patients with congestive heart failure at home.
AB  - Congestive heart failure (CHF) is a major and increasing chronic disease in
      Western society, with a high mortality, morbidity and cost for unplanned hospital
      admissions. Continuous cardiorespiratory monitoring is required to detect Cheyne
      Stokes respiration (CSR). We have tested a new wireless monitoring system and
      compared it with polysomnography (PSG) and respiratory inductance plethysmography
      (RIP) in six CHF patients with CSR in a sleep laboratory. The wireless system
      compared well with RIP for the detection of CSR but less well with PSG, which had
      unexpected but significant respiratory sensing errors that led to
      misclassification of the respiratory disorder present. The wireless system could
      be used to select CHF patients for better-customized treatment at home as part of
      a specialist-supported community telemedicine programme.

PMID- 12217158
TI  - Patients' access to their online electronic health records.
AB  - We surveyed a randomized group of 1050 adult patients stratified for age and sex,
      from a general practice in Oxfordshire, to find out their attitudes to electronic
      health records (EHRs). Eighty-six per cent thought that patients should have the
      right to see their records. While 72% knew that they had the right to see their
      records, only 4% had done so. Private EHR viewing booths with a computer and
      fingerprint identification system were installed in the primary care centre.
      Patients were randomly selected from those who responded to the questionnaire and
      wished to view their EHR. Of the 100 patients who saw their online EHR, 99 found
      the session useful and 84 found their records easy to understand. Three focus
      groups were held with 14 patients who said that they did not want to access their
      EHRs. The reasons patients gave during the focus groups included that they
      trusted their general practitioner and thought it would imply a lack of
      confidence. After the focus groups, 11 patients changed their minds and accessed
      their records. We believe that patient-accessed EHRs will offer substantial
      benefits to patients, health professionals and the National Health Service as a
      whole.

PMID- 12217159
TI  - Explaining the adoption of telemedicine services: an analysis of a paediatric
      telemedicine service.
AB  - Since 1998, over 1300 telemedicine consultations have been provided to 12 schools
      in Kansas City. Despite the success of the programme, effective utilization of
      services has not occurred at all sites. We used a focus group and survey methods
      to investigate barriers to and catalysts for service adoption. The results showed
      that the school nurses strongly supported the programme. They valued its ability
      to provide health-care for the children and they welcomed their enhanced role.
      However, technical complexities and difficulties in obtaining parental consent
      were found to impede adoption. The nurses also expressed frustration with school
      personnel who had a poor understanding of their role in general as well as that
      of the telemedicine service. A new state reimbursement policy may promote greater
      understanding and provide a financial incentive for schools to adopt the
      telemedicine service.

PMID- 12217160
TI  - Restructuring rural continuing medical education through videoconferencing.
AB  - We piloted a videoconferencing continuing medical education programme for rural
      physicians in Alberta and compared its feasibility, acceptability and cost
      implications with currently existing telephone conferencing and regional
      conference programmes. Videoconferencing clearly had advantages over telephone
      conferencing but was not as well appreciated by consumers as the existing
      regional conference programme. Nonetheless, the videoconferencing programme,
      although somewhat more costly than telephone conferencing, was associated with
      considerable cost-savings compared with the regional conference programme. On
      balance, we concluded that further development of the videoconferencing programme
      is warranted and we will slowly replace existing telephone conferencing
      programmes. However, there remains a need for the current regional conference
      programme.

PMID- 12217161
TI  - An integrated nursing and telemedicine approach to vascular care.
AB  - We have developed a telemedicine approach to vascular care for patients being
      managed in primary care. District nurses visit patients in their homes. Clinical
      information and digital photographs can be sent by email to the vascular surgeon
      for assessment. Where appropriate a preliminary teleconsultation between the
      patient and a vascular surgeon, with the nurse in attendance, is held at the
      primary care centre and the management of the patient is agreed. This may include
      referral to surgery. Over eight months six patients with diabetes and peripheral
      ulcers participated in the vascular telemedicine clinic. The average consultation
      time was 12 min (SD 4), which included discussion of the case and negotiation of
      its management. Important outcomes of the new system were the ability to schedule
      patients for rapid referral and to have completed the management of the case
      during the teleconsultation.

PMID- 12217162
TI  - Improving treatment adherence and longitudinal outcomes in patients with a
      serious mental illness by using telemedicine.
AB  - A psycho-educational programme was developed using the health belief model and
      the individual s cognitive model of the disorder and treatment. The participants
      were 51 rural inpatients admitted to a tertiary psychiatric centre. Twenty-four
      inpatients (13 men, 11 women) were discharged using discharge planning by
      videoconference involving the general practitioner, case manager and a family
      member. Patients then received six sessions of the psycho-educational programme.
      A control group of 27 inpatients (16 men, 11 women) were discharged with
      conventional discharge summaries to general practitioners and case managers and
      did not receive the psycho-educational programme. More patients in the control
      group than in the telemedicine group were readmitted to hospital over a 12-month
      period. Significantly more patients in the control group reported medication side
      effects than those in the telemedicine group. Patients in the telemedicine group
      reported greater treatment adherence and compliance than those in the control
      group. When compared with the control group, the telemedicine group reported
      significantly more satisfaction with their treatment and discharge planning.

PMID- 12217163
TI  - The MPEG-4 standard and electronic reporting for mobile, multimedia patient
      records.
AB  - Electronic reporting and transfer of confidential patient data to the electronic
      patient record using Internet-related and wireless technologies can pose threats
      to the security and integrity of data. The MPEG-4 (Moving Pictures Experts Group
      Version 4) standard can enable the seamless integration of text, digitized images
      and video sequences, and the necessary data security protocols for mobile access
      to and transfer of patient information. This standard will improve the quality of
      the electronic patient record as well as the reliability of authentication of
      reports. Applying the standard for patient reporting will also improve ways for
      authorized users to interact with patient records. Easier access to mobile
      multimedia patient records will assist clinicians in documenting patient episodes
      in a more timely and synchronous manner. This will result in better communication
      between health-care team members by allowing them to stay linked and interactive
      even when separated by distances in a telemedicine environment.

PMID- 12217167
TI  - The physiology of cognitive processes. Proceedings of a discussion meeting held
      at The Royal Society. London, United Kingdom. December 5-6, 2001.

PMID- 12217168
TI  - Functional measurements of human ventral occipital cortex: retinotopy and colour.
AB  - Human colour vision originates in the cone photoreceptors, whose spatial density
      peaks in the fovea and declines rapidly into the periphery. For this reason, one
      expects to find a large representation of the cone-rich fovea in those cortical
      locations that support colour perception. Human occipital cortex contains several
      distinct foveal representations including at least two that extend onto the
      ventral surface: a region thought to be critical for colour vision. To learn more
      about these ventral signals, we used functional magnetic resonance imaging to
      identify visual field maps and colour responsivity on the ventral surface. We
      found a visual map of the complete contralateral hemifield in a 4 cm(2) region
      adjacent to ventral V3; the foveal representation of this map is confluent with
      that of areas V1/2/3. Additionally, a distinct foveal representation is present
      on the ventral surface situated 3-5 cm anterior from the confluent V1/2/3 foveal
      representations. This organization is not consistent with the definition of area
      V8, which assumes the presence of a quarter field representation adjacent to V3v.
      Comparisons of responses to luminance-matched coloured and achromatic patterns
      show increased activity to the coloured stimuli beginning in area V1 and
      extending through the new hemifield representation and further anterior in the
      ventral occipital lobe.

PMID- 12217169
TI  - The uses of colour vision: behavioural and physiological distinctiveness of
      colour stimuli.
AB  - Colour and greyscale (black and white) pictures look different to us, but it is
      not clear whether the difference in appearance is a consequence of the way our
      visual system uses colour signals or a by-product of our experience. In
      principle, colour images are qualitatively different from greyscale images
      because they make it possible to use different processing strategies. Colour
      signals provide important cues for segmenting the image into areas that represent
      different objects and for linking together areas that represent the same object.
      If this property of colour signals is exploited in visual processing we would
      expect colour stimuli to look different, as a class, from greyscale stimuli. We
      would also expect that adding colour signals to greyscale signals should change
      the way that those signals are processed. We have investigated these questions in
      behavioural and in physiological experiments. We find that male marmosets (all of
      which are dichromats) rapidly learn to distinguish between colour and greyscale
      copies of the same images. The discrimination transfers to new image pairs, to
      new colours and to image pairs in which the colour and greyscale images are
      spatially different. We find that, in a proportion of neurons recorded in the
      marmoset visual cortex, colour-shifts in opposite directions produce similar
      enhancements of the response to a luminance stimulus. We conclude that colour is,
      both behaviourally and physiologically, a distinctive property of images.

PMID- 12217170
TI  - The temporal resolution of neural codes: does response latency have a unique
      role?
AB  - This article reviews the nature of the neural code in non-human primate cortex
      and assesses the potential for neurons to carry two or more signals
      simultaneously. Neurophysiological recordings from visual and motor systems
      indicate that the evidence for a role for precisely timed spikes relative to
      other spike times (ca. 1-10 ms resolution) is inconclusive. This indicates that
      the visual system does not carry a signal that identifies whether the responses
      were elicited when the stimulus was attended or not. Simulations show that the
      absence of such a signal reduces, but does not eliminate, the increased
      discrimination between stimuli that are attended compared with when the stimuli
      are unattended. The increased accuracy asymptotes with increased gain control,
      indicating limited benefit from increasing attention. The absence of a signal
      identifying the attentional state under which stimuli were viewed can produce the
      greatest discrimination between attended and unattended stimuli. Furthermore, the
      greatest reduction in discrimination errors occurs for a limited range of gain
      control, again indicating that attention effects are limited. By contrast to
      precisely timed patterns of spikes where the timing is relative to other spikes,
      response latency provides a fine temporal resolution signal (ca. 10 ms
      resolution) that carries information that is unavailable from coarse temporal
      response measures. Changes in response latency and changes in response magnitude
      can give rise to different predictions for the patterns of reaction times. The
      predictions are verified, and it is shown that the standard method for
      distinguishing executive and slave processes is only valid if the representations
      of interest, as evidenced by the neural code, are known. Overall, the data
      indicate that the signalling evident in neural signals is restricted to the spike
      count and the precise times of spikes relative to stimulus onset (response
      latency). These coding issues have implications for our understanding of
      cognitive models of attention and the roles of executive and slave systems.

PMID- 12217172
TI  - Exploring the cortical evidence of a sensory-discrimination process.
AB  - Humans and monkeys have similar abilities to discriminate the difference in
      frequency between two consecutive mechanical vibrations applied to their
      fingertips. This task can be conceived as a chain of neural operations: encoding
      the two consecutive stimuli, maintaining the first stimulus in working memory,
      comparing the second stimulus with the memory trace left by the first stimulus
      and communicating the result of the comparison to the motor apparatus. We studied
      this chain of neural operations by recording and manipulating neurons from
      different areas of the cerebral cortex while monkeys performed the task. The
      results indicate that neurons of the primary somatosensory cortex (S1) generate a
      neural representation of vibrotactile stimuli which correlates closely with
      psychophysical performance. Discrimination based on microstimulation patterns
      injected into clusters of S1 neurons is indistinguishable from that produced by
      natural stimuli. Neurons from the secondary somatosensory cortex (S2), prefrontal
      cortex and medial premotor cortex (MPC) display at different times the trace of
      the first stimulus during the working-memory component of the task. Neurons from
      S2 and MPC appear to show the comparison between the two stimuli and correlate
      with the behavioural decisions. These neural operations may contribute to the
      sensory-discrimination process studied here.

PMID- 12217173
TI  - Neuronal activity and its links with the perception of multi-stable figures.
AB  - In order to isolate the neuronal activity that relates to the making of
      perceptual decisions, we have made use of a perceptually ambiguous motion
      stimulus. This stimulus lies on the boundary between two perceptual categories
      that correspond to clockwise and counter-clockwise rotation of a three
      dimensional figure. It consists of a two-dimensional pattern of moving dots that
      are capable of generating these two, distinct, three-dimensional percepts. We
      have studied the responses of neurons in cortical area V5/MT whilst macaque
      monkeys report judgements about the perceptual configuration of this stimulus. We
      extract a quantitative statistic called 'choice probability' that expresses the
      covariation of neuronal activity and perceptual choice. An analysis of choice
      probabilities shows that the pool of neurons involved in the perceptual decisions
      is a tightly constrained subset of the population of sensory neurons relevant to
      the perceptual task.

PMID- 12217171
TI  - The neural basis of the blood-oxygen-level-dependent functional magnetic
      resonance imaging signal.
AB  - Magnetic resonance imaging (MRI) has rapidly become an important tool in clinical
      medicine and biological research. Its functional variant (functional magnetic
      resonance imaging; fMRI) is currently the most widely used method for brain
      mapping and studying the neural basis of human cognition. While the method is
      widespread, there is insufficient knowledge of the physiological basis of the
      fMRI signal to interpret the data confidently with respect to neural activity.
      This paper reviews the basic principles of MRI and fMRI, and subsequently
      discusses in some detail the relationship between the blood-oxygen-level
      dependent (BOLD) fMRI signal and the neural activity elicited during sensory
      stimulation. To examine this relationship, we conducted the first simultaneous
      intracortical recordings of neural signals and BOLD responses. Depending on the
      temporal characteristics of the stimulus, a moderate to strong correlation was
      found between the neural activity measured with microelectrodes and the BOLD
      signal averaged over a small area around the microelectrode tips. However, the
      BOLD signal had significantly higher variability than the neural activity,
      indicating that human fMRI combined with traditional statistical methods
      underestimates the reliability of the neuronal activity. To understand the
      relative contribution of several types of neuronal signals to the haemodynamic
      response, we compared local field potentials (LFPs), single- and multi-unit
      activity (MUA) with high spatio-temporal fMRI responses recorded simultaneously
      in monkey visual cortex. At recording sites characterized by transient responses,
      only the LFP signal was significantly correlated with the haemodynamic response.
      Furthermore, the LFPs had the largest magnitude signal and linear systems
      analysis showed that the LFPs were better than the MUAs at predicting the fMRI
      responses. These findings, together with an analysis of the neural signals,
      indicate that the BOLD signal primarily measures the input and processing of
      neuronal information within a region and not the output signal transmitted to
      other brain regions.

PMID- 12217174
TI  - The role of attention in visual processing.
AB  - Attention to a visual stimulus typically increases the responses of cortical
      neurons to that stimulus. Because many studies have shown a close relationship
      between the performance of individual neurons and behavioural performance of
      animal subjects, it is important to consider how attention affects this
      relationship. Measurements of behavioural and neuronal performance taken from
      rhesus monkeys while they performed a motion detection task with two attentional
      states show that attention alters the relationship between behaviour and neuronal
      response. Notably, attention affects the relationship differently in different
      cortical visual areas. This indicates that a close relationship between neuronal
      and behavioural performance on a given task persists over changes in attentional
      state only within limited regions of visual cortex.

PMID- 12217175
TI  - The neural selection and control of saccades by the frontal eye field.
AB  - Recent research has provided new insights into the neural processes that select
      the target for and control the production of a shift of gaze. Being a key node in
      the network that subserves visual processing and saccade production, the frontal
      eye field (FEF) has been an effective area in which to monitor these processes.
      Certain neurons in the FEF signal the location of conspicuous or meaningful
      stimuli that may be the targets for saccades. Other neurons control whether and
      when the gaze shifts. The existence of distinct neural processes for visual
      selection and saccade production is necessary to explain the flexibility of
      visually guided behaviour.

PMID- 12217176
TI  - Evidence concerning how neurons of the perirhinal cortex may effect familiarity
      discrimination.
AB  - Many studies indicate that recognition memory involves at least two separable
      processes, familiarity discrimination and recollection. Aspects of what is known
      of potential neuronal substrates of familiarity discrimination are reviewed.
      Lesion studies have established that familiarity discrimination for individual
      visual stimuli is effected by a system centred on the perirhinal cortex of the
      temporal lobe. The fundamental change that encodes prior occurrence of such
      stimuli appears to be a reduction in the response of neurons in anterior inferior
      temporal (including perirhinal) cortex when a stimulus is repeated. The neuronal
      responses rapidly signal the presence of a novel stimulus, and are evidence of
      long-lasting learning after a single exposure. Computational modelling indicates
      that a neuronal network based on such a change in responsiveness is potentially
      highly efficient in information theoretic terms. Processes that occur in long
      term depression within the perirhinal cortex provide candidate synaptic plastic
      mechanisms for that underlying the change, but such linkage remains to be
      experimentally established.

PMID- 12217177
TI  - The neural basis of episodic memory: evidence from functional neuroimaging.
AB  - We review some of our recent research using functional neuroimaging to
      investigate neural activity supporting the encoding and retrieval of episodic
      memories, that is, memories for unique events. Findings from studies of encoding
      indicate that, at the cortical level, the regions responsible for the effective
      encoding of a stimulus event as an episodic memory include some of the regions
      that are also engaged to process the event 'online'. Thus, it appears that there
      is no single cortical site or circuit responsible for episodic encoding. The
      results of retrieval studies indicate that successful recollection of episodic
      information is associated with activation of lateral parietal cortex, along with
      more variable patterns of activity in dorsolateral and anterior prefrontal
      cortex. Whereas parietal regions may play a part in the representation of
      retrieved information, prefrontal areas appear to support processes that act on
      the products of retrieval to align behaviour with the demands of the retrieval
      task.

PMID- 12217178
TI  - Against memory systems.
AB  - The medial temporal lobe is indispensable for normal memory processing in both
      human and non-human primates, as is shown by the fact that large lesions in it
      produce a severe impairment in the acquisition of new memories. The widely
      accepted inference from this observation is that the medial temporal cortex,
      including the hippocampal, entorhinal and perirhinal cortex, contains a memory
      system or multiple memory systems, which are specialized for the acquisition and
      storage of memories. Nevertheless, there are some strong arguments against this
      idea: medial temporal lesions produce amnesia by disconnecting the entire
      temporal cortex from neuromodulatory afferents arising in the brainstem and basal
      forebrain, not by removing cortex; the temporal cortex is essential for
      perception as well as for memory; and response properties of temporal cortical
      neurons make it impossible that some kinds of memory trace could be stored in the
      temporal lobe. All cortex is plastic, and it is possible that the same rules of
      plasticity apply to all cortical areas; therefore, memory traces are stored in
      widespread cortical areas rather than in a specialized memory system restricted
      to the temporal lobe. Among these areas, the prefrontal cortex has an important
      role in learning and memory, but is best understood as an area with no
      specialization of function.

PMID- 12217180
TI  - Role of uncertainty in sensorimotor control.
AB  - Neural signals are corrupted by noise and this places limits on information
      processing. We review the processes involved in goal-directed movements and how
      neural noise and uncertainty determine aspects of our behaviour. First, noise in
      sensory signals limits perception. We show that, when localizing our hand, the
      central nervous system (CNS) integrates visual and proprioceptive information,
      each with different noise properties, in a way that minimizes the uncertainty in
      the overall estimate. Second, noise in motor commands leads to inaccurate
      movements. We review an optimal-control framework, known as 'task optimization in
      the presence of signal-dependent noise', which assumes that movements are planned
      so as to minimize the deleterious consequences of noise and thereby minimize
      inaccuracy. Third, during movement, sensory and motor signals have to be
      integrated to allow estimation of the body's state. Models are presented that
      show how these signals are optimally combined. Finally, we review how the CNS
      deals with noise at the neural and network levels. In all of these processes, the
      CNS carries out the tasks in such a way that the detrimental effects of noise are
      minimized. This shows that it is important to consider effects at the neural
      level in order to understand performance at the behavioural level.

PMID- 12217181
TI  - A discovery of real medicine.

PMID- 12217182
TI  - William Shippen, Jr.: pioneer revolutionary war surgeon and father of American
      anatomy and midwifery.

PMID- 12217179
TI  - The prefrontal cortex: categories, concepts and cognition.
AB  - The ability to generalize behaviour-guiding principles and concepts from
      experience is key to intelligent, goal-directed behaviour. It allows us to deal
      efficiently with a complex world and to adapt readily to novel situations. We
      review evidence that the prefrontal cortex-the cortical area that reaches its
      greatest elaboration in primates-plays a central part in acquiring and
      representing this information. The prefrontal cortex receives highly processed
      information from all major forebrain systems, and neurophysiological studies
      suggest that it synthesizes this into representations of learned task
      contingencies, concepts and task rules. In short, the prefrontal cortex seems to
      underlie our internal representations of the 'rules of the game'. This may
      provide the necessary foundation for the complex behaviour of primates, in whom
      this structure is most elaborate.

PMID- 12217183
TI  - Donor-site complications in vascularized bone flap surgery.
AB  - Microvascular osteocutaneous free flaps have given reconstructive surgeons a
      powerful tool in the reconstruction of composite defects in head and neck
      surgery. Radial forearm, scapula, iliac crest, and fibula flaps have been used
      extensively in mandibular reconstruction. The inevitable donor-site morbidity of
      these osteocutaneous flaps has received less attention than the reconstructive
      advantages. We have reviewed the literature for each type of flap to determine
      the kind, incidence, and consequences of flap associated morbidity. In the
      future, tissue-engineered prefabricated free flaps might play an important role.

PMID- 12217184
TI  - The effects of a broad-spectrum matrix metalloproteinase inhibitor on
      characteristics of wound healing.
AB  - This study investigates the effects of a broad-spectrum matrix metalloproteinase
      inhibitor (MMP-i) on the rate of closure, hydroxyproline deposition, and
      macrophage infiltration in healing wounds. Full-thickness excisional wounds were
      created on the dorsal surface of hairless mice. Two experimental groups were used
      to measure rates of wound closure: (a) MMP-i administration (0.03, 0.3, 3.0, and
      30 microg/mL) on days 0-1 postwounding (inflammatory phase) and (b) MMP-i
      administration (0.03, 0.3, 3.0, and 30 microg/mL) on days 6-8 postwounding
      (proliferative phase). Additionally, hydroxyproline deposition and percent
      macrophage infiltration were measured in skin wound margins on days 2, 8, and 16
      postwounding. MMP-i administration at concentrations of 0.03, 0.3, and 3.0
      microg/mL on days 0-1 postwounding significantly (p <.05) increased the rate of
      wound closure. No significant effect on the rate of wound closure was observed
      with MMP-i administration on days 6-8 postwounding. Hydroxyproline deposition was
      significantly (p <.05) increased on day 8 postwounding, and the percent
      macrophage infiltration was significantly (p <.05) decreased on day 2
      postwounding by MMP-i administration on days 0-1 postwounding. These experiments
      demonstrate that MMP-i administration during the inflammatory phase significantly
      affects several characteristics of wound healing. We postulate that these effects
      may be attributed to decreased degradation of ECM components, increased
      concentrations of endogenous growth factors, and a shortened inflammatory phase.

PMID- 12217185
TI  - Ultrastructural alterations of primary human liver sinusoidal cells in patients
      treated for peritonitis.
AB  - Acute peritonitis is still associated with a high mortality rate. Bacterial
      toxins are rapidly cleared from the peritoneal cavity and may induce general
      sepsis. The hepatic sinusoidal cells are part of the primary defence against
      these toxins. The object of this study was to examine ultrastructural alterations
      of human sinusoidal liver cells from patients undergoing surgical treatment for
      peritonitis. Liver specimens, obtained from five patients treated with programmed
      interval peritoneal lavages for peritonitis, were analyzed by electron
      microscopy. Despite interindividual differences in etiology of peritonitis, the
      detected ultrastructural alterations displayed a high degree of similarity.
      Kupffer cells displayed enhanced phagocytotic activity. Numerous Kupffer cell
      lymphocyte contacts were observed. Notably, the morphological appearance of the
      endothelial cells resembled that of an activated phagocytotic cell. The
      ultrastructural alterations peaked on day 7, and regressed during the course of
      treatment. Our findings demonstrate that major changes occur in the
      ultrastructural appearance of both Kupffer cells and sinusoidal endothelial cells
      in patients with acute peritonitis treated successfully with programmed interval
      peritoneal lavages. Our data suggest that in peritonitis, a septic spread of
      toxins and antigens may be modulated by sinusoidal liver cells.

PMID- 12217186
TI  - Myocardial performance after cardiopulmonary bypass and cardioplegic arrest:
      impact of na+/h+ exchanger inhibition.
AB  - This study was designed to determine if pretreatment with a sodium/hydrogen
      exchange inhibitor (EMD 96 785) improves myocardial performance and reduces
      myocardial edema after cardioplegic arrest (CPA) and cardiopulmonary bypass
      (CPB). Anesthetized canines (n = 18) were instrumented with vascular catheters,
      myocardial ultrasonic crystals, and left ventricle (LV) micromanometer to measure
      preload recruitable stroke work (PRSW), +dP/dt(max), and cardiac output. Serial
      myocardial tissue water content (MWC) was determined from sequential biopsy.
      After baseline measurements, hypothermic (28 degrees C) cardiopulmonary bypass
      was initiated. CPA was maintained for 2 h, followed by reperfusion/rewarming and
      separation from CPB. PRSW and myocardial tissue water were measured at 30, 60,
      and 120 min after CPB. EMD 96 785 (3 mg/kg) was given 15 min prior to CPB.
      Controls received the same volume of saline vehicle. It was found that MWC
      increased from baseline in both EMD 96 785 and controls with CPB/CPA. PRSW
      decreased from baseline at 30 and 60 min post CPB/CPA in controls; PRSW did not
      decrease from baseline with EMD 96 785, and was statistically greater at 30 and
      60 min post CPB/CPA compared to controls. Thus, Na(+)/H(+) exchanger inhibition
      with EMD 96 785 (3 mg/kg) pretreatment improves post-CPB/CPA myocardial
      performance without reducing myocardial edema. Na(+)/H(+) exchanger inhibition
      during cardiac procedures using CPB/CPA may be a useful adjunct to improve
      immediate post-CPB/CPA myocardial performance.

PMID- 12217187
TI  - The mechanical influence of tissue engineering techniques on tracheal strength:
      an experimental study on sheep trachea.
AB  - Tissue engineering is an attractive concept for facilitating the transplantation
      of different tissue types with a low immunogeneity and a well-preserved tissue
      structure. We examined the influence of treatment with trypsin/ethylenediamine
      tetraacetic acid (EDTA) on the mechanical properties of tracheae. Fresh sheep
      tracheae were stored in a trypsin/EDTA solution for various periods of time (24,
      46, and 72 h) and their breaking strength was subsequently examined. The results
      were compared with native trachea. The treatment with trypsin/EDTA results in a
      considerable reduction of the mechanical stability under load, in this case
      compared with the tensile strength, that does not correlate with the results
      obtained from light-optical microscopy. The results from this study reveal that
      tissue preparation with trypsin/EDTA does not seem to be a suitable method of
      preparatory treatment of tracheae intended for transplantation.

PMID- 12217188
TI  - A rat model for the study of intestinal heterotopic gastropathy.
AB  - This study analyzes an experimental model for the study of reactions from gastric
      tissue exposed to enteric environment. Morphological studies were performed by
      histological, histochemical and immunohistochemical methods, using formalin-fixed
      biopsies of full-wall-thickness gastric implants in a whole-wall jejunal defect.
      These grafts suffered severe lesions, characterized by chronic atrophic
      gastritis, foveolar hyperplasia, glandular cystic transformation, and intestinal
      metaplasia. Increase in acidic mucins was also observed. There was no
      proliferating cell nuclear antigen (PCNA) overexpression. The results suggest
      that this model can be useful to investigate the heterotopic grastropathy and can
      be applied in further research studies.

PMID- 12217190
TI  - Allogeneic peripheral blood stem cell transplantation in beta-thalassemia.
AB  - Six transfusion-dependent beta-thalassemia major patients were treated with
      allogeneic peripheral blood stem cell (PBSC) transplant. The donors were HLA
      identical siblings except one donor who was a father with one-antigen mismatch of
      HLA-B loci. The donors were mobilized with G-CSF and PBSC was infused without
      manipulation. Engraftment was documented in all patients. Acute graft versus host
      disease (GvHD) was present in 4 patients but could be controlled with steroid
      or/and ATG. One patient died of hepatic veno-occlusive disease (HVOD) and
      survivors were all transfusion independent (ex-thalassemia). Chronic GvHD
      occurred in one patient. Allogeneic PBSC transplantation could achieve disease
      free survival in beta-thalassemia major patients.

PMID- 12217191
TI  - Infiltrations of Epstein-Barr virus-carrying cells in granular lymphocyte
      proliferative disorders corresponding to chronic active Epstein-Barr virus
      infection.
AB  - A 21-year-old man with granular lymphocyte-proliferative disorders (GLPD)
      associated with chronic active Epstein-Barr virus (EBV) infection is described.
      Chromosomal analyses revealed several clonal abnormalities and two of them were
      mainly repetitious. High copy numbers of monoclonal EBV genome were also detected
      in the proliferative large granular lymphocytes (LGLs), indicating the monoclonal
      expansion of EBV-infected LGLs. The patient had an indolent course for several
      years, and there was no evidence of infiltrations of his bone marrow until the
      end stage. At autopsy, microscopic studies revealed marked infiltrations of LGL
      in the liver and spleen, and the infiltrating cells were NK-cell immunophenotype.
      The infiltrated LGLs showed latency I.

PMID- 12217192
TI  - Plasma levels of the von Willebrand factor-cleaving protease in physiological and
      pathological conditions in children.
AB  - The hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP)
      are rare disorders characterized by thrombocytopenia, hemolytic anemia, and
      ischemic organ failure due to thrombotic occlusions in arterioles. The recent
      observation that a von Willebrand factor-cleaving protease (VWF-CP) is low in the
      plasma of patients with TTP but normal in those with HUS has potentially offered
      a new specific tool for differential diagnosis. In this study, the authors
      evaluated the plasma levels of the VWF-CP during the neonatal state and healthy
      childhood and in some pathological pediatric conditions. The protease was
      measured in 16 healthy newborns, 20 healthy children aged 5-18 years, patients
      with diabetes mellitus type 1 (n = 7), acute viral hepatitis (n = 10), chronic
      viral hepatitis (n = 10), transfusion-dependent beta-thalassemia major (n = 10),
      acute varicella infection (n = 11), the nephrotic syndrome (n = 11), and familial
      Mediterranean fever (n = 10). Mean protease levels were significantly lower in
      newborns than in healthy children (50.5 +/- 16.1% vs. 83.3 +/- 16.3%)(p = .0001).
      In patients with acute viral hepatitis, protease levels were also significantly
      reduced (40.2 +/- 27% v s. 83.3 +/- 16.3% in healthy children)(p = .0001). Other
      patient groups had normal protease levels. In conclusion, low protease levels are
      far from being a specific beacon for TTP. The current paradigm that a single
      laboratory test may enable physicians to distinguish TTP from HUS seems to be
      challenged by these and other findings.

PMID- 12217193
TI  - Treatment results of osteosarcoma of the extremity in children and adolescents at
      Ege University Hospital.
AB  - Twenty-five patients were treated for osteosarcoma of the extremity at Ege
      University Hospital. Eight of them were metastatic. All patients received
      cisplatin, doxorubicin, ifosfamide, and methotrexate preoperatively. Twenty-three
      patients underwent surgery at around week 15 (11-18 weeks). All but one underwent
      limb-sparing surgery. While good responders continued to receive the same drugs,
      poor responders were given the same regimen before 1996, but high-dose ifosfamide
      alone after 1996. For all patients the projected event-free survival (EFS) rates
      were 63.5% at 2 years and 53% at 5 years. The projected overall survival (OS)
      rates were 72% at 2 years and 62% at 5 years. For nonmetastatic patients, 5-year
      EFS and OS rates were 67% as compared with metastatic patients (25 and 50%)(p =.
      01 for EFS; p > .05 for OS). The results show that nonmetastatic patients with
      osteosarcoma of the extremity have favorable prognosis on this therapy regimen,
      allowing a high rate of limb-sparing surgery.

PMID- 12217194
TI  - Variability in dose intensity of high-dose methotrexate for nonmetastatic
      osteosarcoma.
AB  - The authors evaluated their ability to maintain planned dosing schedules for high
      dose methotrexate (HD-MTX) in patients with nonmetastatic osteosarcoma. Twenty
      seven patients who received therapy according to 2 POG protocols (8651 and 9351),
      both of which included HD-MTX (12 g/m(2)/week for 2 consecutive weeks), between
      1988 and 1998 were studied. Significantly fewer HD-MTX infusions were given on
      the second week to patients treated on POG 9351 (33 vs. 93%; p < .0001). The
      hydration guidelines were identical and there was no difference in peak serum MTX
      levels either within or between protocols. Differences in the administration of
      combination chemotherapy in 9351 compared to 8651 may have contributed to the
      increased toxicity associated with HD-MTX on 9351, although this is speculative.
      The use of HD-MTX should be carefully planned so that it does not decrease its
      dose intensity or that of other effective agents.

PMID- 12217195
TI  - Splenic function in Omani children with sickle cell disease: correlation with
      severity index, hemoglobin phenotype, iron status, and alpha-thalassemia trait.
AB  - The prevalence of functional asplenia in Omani children with sickle cell disease
      (SCD) has not been previously defined. In this study, the authors aim to compare
      the natural history of splenic dysfunction in their patients to other reports.
      The splenic function was studied in 72 Omani patients with sickle cell disease
      (50 homozygous for hemoglobin S (HbS-S), 11 double heterozygotes for HbS and
      beta(0)-thalassemia (HbS-beta(0)-thal), 5 HbS-beta(+)-thal, 5 patients with
      hemoglobin S-D disease, and 1 child with hemoglobin S oman trait) aged 4.8-16
      years, using (99m)Tc-labeled tin colloid scintigraphy. The study revealed 4
      groups according to their colloid uptake: group I included 20 patients (28%) with
      normal splenic function; group II, 6 patients (8%) with mild hyposplenism; group
      III, 20 (28%) with severe hyposplenism; and group IV, 26 (36%) patients with
      functional asplenia. Overall, more than 60% of them had preserved splenic
      function. Except for HbS-beta(+) patients, the developmental pattern of
      hyposplenism was not different among the different Hb phenotypes. Factors
      associated with preservation of spleen function in these patients were larger
      splenic size (p < .01), less clinical severity (p < .05), lower MCH (p < .01),
      higher HbF (p < .001), and presence of alpha-thalassemia trait (p < .05).

PMID- 12217196
TI  - Ganglianeuroma: radiological and metabolic features in 4 children.
AB  - Ganglioneuroma constitutes a benign and surgically treatable tumor. The authors
      studied 4 patients with histopathologically proven ganglioneuroma focusing on
      radiological and metabolic features. The results confirm previous investigations
      that have shown metabolic activity in ganglioneuroma and characteristic patterns
      in imaging studies. Although for definite diagnosis tissue investigation is
      required, certain clinical and radiological features are suggestive of
      ganglioneuroma.

PMID- 12217197
TI  - Transgenic IL-2 expression in Ewing tumor cell lines after transfection with
      Starburst dendrimers and cationic liposomes.
AB  - Immunotherapy with IL-2-transduced cells requires efficient methods of gene
      transfer. Nonviral methods have been studied intensively in recent years. This
      study examined whether tumor and fibroblast cell lines established from Ewing
      tumor patients could be efficiently transfected with the IL-2 gene. Starburst
      dendrimers (Superfect), a novel transfection reagent, were chosen for a
      transfection study and optimal conditions for gene transfer were evaluated. Three
      Ewing tumor cell lines and 3 fibroblast cell lines obtained from Ewing tumor
      patients were analyzed. The concentration of IL-2 in the supernatant of
      transfected cells was measured by ELISA. All three Ewing tumor cell lines
      transfected by Starburst dendrimers yielded higher IL-2 levels than after
      lipofection. In contrast to lipofection, expression of IL-2 increased with time
      and peaked later. In one of three tested fibroblast cell lines, transfection
      using Superfect yielded higher IL-2 levels. IL-2 production was generally lower
      in fibroblasts as compared to Ewing tumor cell lines. Given the low toxicity of
      Superfect reagent and the high efficiency of transfection, this method seems to
      be ideal for clinical studies on the immunotherapy of Ewing tumors.

PMID- 12217198
TI  - Acute lymphoblastic leukemia and hepatoblastoma in a family.
AB  - Acute lymphoblastic leukemia is the most common and hepatoblastoma is a rare
      malignancy diagnosed in children. Their report on an Iranian boy with acute
      lymphoblastic leukemia diagnosed at the age of 2 years; 20 months later his 10
      month-old sister was referred to their hospital with hepatoblastoma. The
      occurrence of such two types of cancer is rare in a family.

PMID- 12217199
TI  - Intermittent 20q- and consistent i(7q) in a patient with Shwachman-Diamond
      syndrome.
AB  - Shwachman Diamond syndrome (SDS) is a genetic disorder characterized by
      pancreatic hypoplasia, recurrent infection and bone marrow dysfunction. Some
      cases have an abnormality of chromosome 7, such as isochromosome 7q (i(7q)),
      which may be associated with the development of leukemia. We present a boy who
      was diagnosed with SDS at 19 months of age. From age 5-14 years, bone marrow
      cytogenetics has shown a consistent abnormality - i(7q), with an intermittent
      separate abnormality - deletion 20q, from age 11 years. During this time, the boy
      has been clinically well without leukemic signs, managed conservatively. We
      suggest that deletion 20q may be a non random secondary change in SDS with i(7q).

PMID- 12217200
TI  - Traumatic optic neuropathy complicating combined idiopathic thrombocytopenia and
      neutropenia.

PMID- 12217201
TI  - The relationship between neurobehavioural problems of severe traumatic brain
      injury (TBI), family functioning and the psychological well-being of the
      spouse/caregiver: path model analysis.
AB  - This study used a modern theory of stress as a framework to strengthen the
      understanding of the relationship between neurobehavioural problems of TBI,
      family functioning and psychological distress in spouse/caregivers. The research
      was an ex post facto design utilising a cross-sectional methodology. Path
      analysis was used to determine the structural effect of neurobehavioural problems
      on family functioning and psychological distress. Forty-seven female and 17 male
      spouse/caregivers of partners with severe TBI were recruited. Spouse/caregivers
      who reported partners with TBI as having high levels of behavioural and cognitive
      problems experienced high levels of unhealthy family functioning. High levels of
      unhealthy family functioning were related to high levels of distress in
      spouse/caregivers, as family functioning had a moderate influence on
      psychological distress. Furthermore, indirect effects of behavioural and
      cognitive problems operating through family functioning intensified the level of
      psychological distress experienced by spouse/caregivers. Additionally,
      spouse/caregivers who reported high levels of behavioural, communication and
      social problems in their partners also experienced high levels of psychological
      distress. This study was significant because the impact of TBI on the
      spouse/caregiver from a multidimensional perspective is an important and under
      researched area in the brain injury and disability field.

PMID- 12217202
TI  - Performance on measures of executive function following pediatric traumatic brain
      injury.
AB  - OBJECTIVE: To investigate the relationships among age at injury, neuroanatomic
      lesion location, and measures of executive function (EF) following paediatric
      traumatic brain injury (TBI). METHODS: EF was assessed in 68 children (aged 7-15)
      with moderate-to-severe TBI 1 year post-injury. EF tests included: (1) Tower of
      Hanoi (TOH), a measure of problem solving ability, (2) Wisconsin Card Sorting
      Test (WCST), a measure of categorization and ability to shift cognitive
      strategies, (3) Letter Fluency (LF), a measure of novel lexical search and rule
      governed word generation. EF variables included number of moves needed to achieve
      a 3-ring solution on the TOH, number of perseverative and non-perseverative
      errors on the WCST, and number of words generated on LF. Intellectual functioning
      was also assessed using the Verbal Intellectual Quotient (VIQ) from the Wechsler
      Intelligence Scale from Children-3rd edn (WISC-III). Data from standardized MRIs,
      performed at 3-months post-injury, were available for all subjects and were used
      to determine lesion location, lesion volumes, and total number of lesions. The
      relationships among EF, lesion variables (frontal lesion volume, extrafrontal
      lesion volume, total number of lesions) and age at injury were examined. Pre
      injury special education services and attention deficit hyperactivity disorder
      (ADHD) were controlled for. RESULTS: Younger age at injury was associated with
      more perseverative errors on the WCST and worse performance on LF. Frontal lesion
      volume was not predictive of performance on any measures of EF. Greater
      extrafrontal lesion volume and total number of lesions were predictive of worse
      performance on LF. When controlling for pre-injury special education placement
      and pre-injury ADHD, there was little change in the results. CONCLUSIONS: Younger
      age at injury places children at greater risk of impairment on measures of EF.
      Performance on measures of EF depends on brain variables other than frontal lobes
      including extrafrontal cortical brain areas and total number of lesions. The
      relationship between extrafrontal brain regions and EF suggests that domain
      specific cognitive content (i.e. language or visuospatial analysis), mediated by
      the parietal or temporal lobes, may disrupt underlying cognitive processes
      necessary for successful performance on measures of EF. In addition, the
      association between total number of lesions and EF may be related to
      disconnections and disruption of frontal/subcortical systems.

PMID- 12217203
TI  - Mild traumatic brain injury (MTBI): assessment and treatment procedures used by
      speech-language pathologists (SLPs).
AB  - The purposes of this study were to identify how individuals with MTBI are
      assessed, to determine the referral process to and from speech-language
      pathologists (SLPs), to describe the frequency, structure, and nature of
      treatment, to identify how individuals with MTBI and their families are educated
      about the injury and counselled, and to assess current follow-up procedures. One
      hundred and forty-three hospital and rehabilitation centre based SLPs from North
      Carolina and Illinois responded to a survey developed to address these areas of
      interest. Findings indicated current diagnostic tools used by SLPs lack the
      sensitivity to detect the subtle cognitive communication deficits associated with
      MTBI, referral and follow-up procedures are not sufficiently implemented in
      facilities to meet the growing needs of individuals with MTBI, and SLPs would
      benefit from increased training regarding the management of individuals with MTBI
      including educating and counselling patients and their families.

PMID- 12217204
TI  - Ambulatory efficiency in persons with acquired brain injury after a
      rehabilitation intervention.
AB  - OBJECTIVE: the purpose was to assess changes in cardiorespiratory responses to
      treadmill ambulation in a sample of patients with acquired brain injury. RESEARCH
      DESIGN: a repeated measures, pre-test post-test design examined differences
      between submaximal and peak responses at admission and discharge. METHODS AND
      PROCEDURES: forty individuals (29 male, 11 female) were studied. Subjects
      performed an ambulatory treadmill test during which heart rate (EKG) and oxygen
      consumption (VO(2)) were monitored continuously. Total ambulation time (TAT) was
      also recorded. RESULTS: TAT increased from 10.3 (SD 3.1) minutes to 13.6 (SD 3.5)
      minutes (p < 0.01). Peak HR did not change (168 (SD 20) bpm vs. 167 (SD 21 bpm))
      nor did peak VO(2) (23.5 (SD 6.6)ml/min/kg vs. 24.3 (SD 6.4)ml/min/kg; p = 0.09).
      However, both sub-maximal HR and VO(2) decreased (p < 0.05) between 2-12 minutes
      when most subjects were still capable of ambulating. CONCLUSIONS: the results
      suggest an improvement in both aerobic capacity and movement efficiency. Further
      controlled studies will be necessary to distinguish between cardiorespiratory and
      neuromuscular adaptations. The changes observed should allow for greater
      community participation and functional independence after discharge.

PMID- 12217205
TI  - Electroencephalography in primary diagnosis of mild head trauma.
AB  - OBJECTIVE: the aim of this study was to compare the clinical examination and EEG
      examination regarding their relevance in diagnosing cerebral function changes in
      early head trauma. METHODS: ninety four male patients who suffered from mild head
      trauma (GCS 13-15) were assigned into two groups. The first group fulfilled at
      least one sign of cerebral concussion (amnesia, anisocoria, changes of vigilance
      or vegetative symptoms such as vomiting), the second group did not. EEG
      examination was performed in both groups. RESULTS: in the first group, more
      pathologic EEG records were found. These findings showed a statistical
      significance (p = 0.019). The concussion group showed more focal changes (p =
      0.283) and specific changes (p = 0.317), but they were statistically not
      significant. CONCLUSION: EEG can be used for detecting pathologic unspecific
      alterations with a high accuracy, but is not useful in specifying the findings
      for an exact diagnosis.

PMID- 12217206
TI  - Early S-100B serum level correlates to quality of life in patients after severe
      head injury.
AB  - PURPOSE: S-100B protein is a new possible indicator of brain damage after severe
      head injury. In outcome assessment there is an increasing focus on measures of
      health outcome incorporating the person's own perspective. Therefore, the aim of
      the study was to investigate the correlation of early S-100B serum level to the
      quality of life. METHOD: fifty-one patients with severe head injury were included
      in a prospective study. Blood samples were taken on admission (mean 2.5 hours).
      The outcome was assessed at follow-up using the Glasgow Outcome Scale and a
      questionnaire according to Blau to assess the quality of life. RESULTS: high
      serum concentrations of S-100B on admission correlate to unfavourable outcome
      according to the GOS (4.9 micro g/l vs 1.6 micro g/l, mean, p < 0.0008). In
      addition, the S-100B serum concentrations on admission correlate to quality of
      life in the survivor group. Patients with S-100B serum levels < or = 0.5 micro
      g/l scored 71.4 points (mean) on the QoL index compared to patients with elevated
      S-100B concentrations, who scored 55.4 points (mean, p < 0.05). CONCLUSION: S
      100B seems to be able to assess the extent of primary brain damage after trauma.

PMID- 12217207
TI  - Self-regulatory learning and generalization for people with brain injury.
AB  - PRIMARY OBJECTIVE: brain injury can result in the loss of previous learnt
      behaviours that affect an individual's daily functioning. The use of self
      regulation helps the individual to relearn the lost behaviours by bringing
      him/her to self-conscious level through independent and reflective learning
      derived using a social cognitive perspective. The purpose of this paper is to
      report on clinical observations made with the use of self-regulation in people
      with brain injury during the relearning of lost functions. METHODS AND
      PROCEDURES: daily tasks were used to assess the relearning ability of the
      subjects pre- and post-programme. EXPERIMENTAL INTERVENTION: one-week self
      regulatory training on five selected daily tasks. MAIN OUTCOMES AND RESULTS:
      these provisory observations would suggest that, with specific guidance for
      people with different needs, such as with impaired cognitive function and
      depression, self-regulation is effective in enhancing their relearning.
      CONCLUSION: Self-regulatory training is effective in enhancing the relearning of
      lost functions.

PMID- 12217208
TI  - The impact of intrathecal baclofen on gastrointestinal function.
AB  - Intrathecal baclofen (ITB) application has become the first choice in the
      management of otherwise intractable generalized spasticity. The mechanism whereby
      ITB alleviates increased skeletal muscle tone is generally accepted; however,
      less is known about its effect on smooth muscles. The authors present two
      patients who developed a paralytic ileus during ITB infusion for supraspinal
      spasticity. In addition, they performed a retrospective chart analysis of another
      12 patients receiving ITB with respect to their intestinal function. They
      calculated the cumulative sum of days without bowel movements plus the cumulative
      sum of interventions intended to promote intestinal peristalsis before and during
      ITB treatment. Intestinal function deteriorated in 10, remained unchanged in one,
      and improved in three patients compared to baseline, irrespective of concomitant
      oral baclofen medication. This is the first study addressing a previously
      unnoticed, but potentially deleterious side effect of ITB treatment. The findings
      suggest, however, that close observation of intestinal activity in conjunction
      with the generous use of prokinetic, laxantic or eubiotic drugs may allow for
      continuation of ITB treatment, even in particularly sensitive patients.

PMID- 12217209
TI  - Effects of delayed treatment with transforming growth factor-beta soluble
      receptor in a three-dose bleomycin model of lung fibrosis in hamsters.
AB  - Transforming growth factor-beta (TGF-beta) plays a pivotal role in an exaggerated
      synthesis and accumulation of collagen in fibrotic disorders of many organs. We
      have previously demonstrated that repeated intratracheal (IT) instillation of TGF
      beta soluble receptor (TR) in hamsters markedly decreased the bleomycin (BL)
      induced lung fibrosis in response to a single dose. The present study was carried
      out in a 3-dose BL-hamster model of lung fibrosis to better evaluate the
      therapeutic potential of TR. Three doses of BL (2.5, 2.0, and 1.5 U/4 mL/kg) or
      an equivalent volume of isotonic saline was administered IT consecutively at
      weekly intervals, and phosphate-buffered saline (PBS) or TR (4 nmol/0.3
      mL/hamster) by the same route twice a week, starting after the 2nd BL or 3rd BL
      dose. Twenty-one days after the 3rd dose of BL instillation, the hamsters were
      killed for bronchoalveolar lavage (BAL) and biochemical and histopathological
      analyses. The results showed that treatment with TR starting after either the 2nd
      or 3rd dose of BL caused significant reduction in BL-induced lung fibrosis, as
      demonstrated by marked decreases in the hydroxyproline level and prolyl
      hydroxylase activity of the lungs. Histopathological evaluation of the lungs also
      revealed that the hamsters in both BL+TR groups had markedly fewer fibrotic
      lesions than hamsters in BL+PBS group. These results demonstrate the beneficial
      effects of delayed treatment with TR in attenuating the progression of ongoing
      fibrotic process and suggest its potential therapeutic uses in the management of
      lung fibrosis in humans.

PMID- 12217210
TI  - Endotoxin potentiates ozone-induced pulmonary chemokine and inflammatory
      responses.
AB  - Urban air consists of a combination of environmental pollutants. Recent studies
      have suggested that normally innocuous doses of a particular pollutant may be
      rendered more toxic to the lung if primed by earlier events. Pulmonary
      inflammation has been observed in humans and in many animal species after
      endotoxin and ozone exposures. The present study was designed to test the
      hypothesis that inhalation of low levels of endotoxin following ozone exposure
      will potentiate ozone-induced lung injury. We exposed 8-week-old C57BL/6J mice to
      1 ppm ozone for 24 hours; inhalation of low-dose endotoxin (37.5 EU) for 10
      minutes; or 1 ppm ozone immediately followed by endotoxin inhalation (37.5 EU).
      The mice were examined 4 or 24 hours post exposure. After 24 hours of recovery,
      significant increases were measured in bronchoalveolar lavage (BAL) fluid levels
      of protein and lavageable polymorphonuclear neutrophils (PMNs) after coexposure
      to ozone followed immediately by endotoxin inhalation as compared to exposures
      individually. Messages encoding macrophage inflammatory protein (MIP)-1beta, MIP
      1alpha, MIP-2, monocyte chemoattractant protein (MCP)-1, interleukin (IL)-1alpha,
      IL-1beta, IL-1Ra, IL-6, and Macrophage Migration Inhibitory Factor (MIF) were
      significantly elevated 24 hours post ozone followed by endotoxin as compared to
      exposure to ozone or endotoxin individually. These results demonstrate that
      preexposure to ozone, which primarily attacks the epithelium, can cause
      sensitization to a secondary stimulus through a mechanism that culminates in a
      greater and prolonged onset of inflammatory cell recruitment, pulmonary edema,
      and increased expression of chemokine and cytokine messages.

PMID- 12217211
TI  - A murine model of cigarette smoke-induced pulmonary inflammation using
      intranasally administered smoke-conditioned medium.
AB  - To date, few animal models of chronic obstructive pulmonary disease (COPD) exist
      that are ideal for the evaluation of pathophysiology, as they typically require
      many months of cigarette smoke exposure in inhalation facilities. Here we show
      that pulmonary inflammation and some of the inflammatory hallmarks of COPD can be
      induced in mice by cigarette smoke-conditioned media (CS) administered by the
      intranasal route. Balb/c mice were challenged with CS for up to 40 days. At the
      end of smoke treatment, mice were sacrificed and bronchoalveolar lavage (BAL)
      fluid collected. Total cell counts and cell differentials were performed. Enzyme
      linked immunosorbent assays (ELISAs) for KC and tumor necrosis factor alpha (TNF
      alpha) were performed on BAL fluid. Lungs and nasal cavities were examined
      histologically. Intranasal CS treatment significantly increased BAL neutrophils,
      lymphocytes, KC, TNF-alpha, and mucin. Changes in pulmonary reactivity to
      methacholine were also observed in mice challenged with CS for 40 days. The model
      described above demonstrates that within 1 to 8 weeks of intranasal instillation
      of CS, mice develop pulmonary inflammation and cellular lung changes that are
      characteristic of human COPD and therefore may be a good short-term in vivo model
      that can be utilized to monitor intervention strategies targeted for COPD.

PMID- 12217212
TI  - A new approach to detect structural differences in lung parenchyma using digital
      image analysis.
AB  - Morphometric investigations using a point and intersection counting strategy in
      the lung often are not able to reveal the full set of morphologic changes. This
      happens particularly when structural modifications are not expressed in terms of
      volume density changes and when rough and fine surface density alterations cancel
      each other at different magnifications. Making use of digital image processing,
      we present a methodological approach that allows to easily and quickly quantify
      changes of the geometrical properties of the parenchymal lung structure and
      reflects closely the visual appreciation of the changes. Randomly sampled digital
      images from light microscopic sections of lung parenchyma are filtered,
      binarized, and skeletonized. The lung septa are thus represented as a single
      pixel wide line network with nodal points and end points and the corresponding
      internodal and end segments. By automatically counting the number of points and
      measuring the lengths of the skeletal segments, the lung architecture can be
      characterized and very subtle structural changes can be detected. This new
      methodological approach to lung structure analysis is highly sensitive to
      morphological changes in the parenchyma: it detected highly significant
      quantitative alterations in the structure of lungs of rats treated with a
      glucocorticoid hormone, where the classical morphometry had partly failed.

PMID- 12217213
TI  - Inhibition of endogenous nitric oxide during endotoxemia in awake sheep - effects
      of Nomega-nitro-l-arginine on the distribution of pulmonary vascular resistance
      and prostanoid products.
AB  - We examined the effects of endogenous nitric oxide (NO) inhibition on the
      longitudinal distribution of pulmonary vascular resistance and on arachidonic
      acid metabolism during endotoxemia in awake sheep. Mean pulmonary artery (Ppa),
      left atrial (Pla), and systemic artery pressure (Psa) were continuously measured,
      and cardiac output (CO) was continuously monitored by an implanted ultrasonic
      flow probe. We advanced a 7-French Swan-Ganz catheter into distal pulmonary
      artery and measured the pulmonary microwedge pressure (Pmw) with the balloon
      deflated, allowing calculation of upstream pulmonary vascular resistance (PVRup =
      [Ppa - Pmw]/CO) and down-stream PVR (PVRdown = [Pmw - Pla]/CO), respectively. In
      paired studies, endotoxin (1 micro g/kg) was infused over 30 minutes with and
      without N(omega)-nitro-L-arginine (NLA) treatment. NLA (20 mg/kg) was
      administered 30 minutes before endotoxin infusion. Endotoxin caused increases in
      PVRup and PVRdown. Pretreatment with NLA increases PVRup at baseline and enhanced
      increases in both PVRup and PVRdown during endotoxemia. Plasma level of
      thromboxane B(2) (TxB(2)) and prostacyclin (6-keto = PGF(1alpha)) significantly
      increased 1 hour after endotoxin administration (TxB(2), 308.3 +/- 94.8 [SE] to
      2163.5 +/- 988.5 pg ml(-1), P <.05; 6-keto=PGF(1alpha), 155.6 +/- 91.4 to 564.9
      +/- 131.8 pg ml(-1), P <.05), but the increased levels were similar to those in
      the NLA-pretreated animals. We conclude that endogenous NO mainly regulates
      precapillary vascular tone at baseline, and that NO modulated pre- and
      postcapillary vascular constriction during endotoxemia in sheep. It appears that
      cyclooxygenase production in response to endotoxin is unaffected by NO and its
      vascular effects.

PMID- 12217214
TI  - L-carnitine does not exert any in vitro relaxant effect in Guinea pig trachea,
      lung parenchyma and human bronchial tissue.
AB  - The aim of the present study was to investigate the probable in vitro relaxant
      effect of carnitine in guinea pig trachea, guinea pig lung parenchymal strips,
      and human bronchial tissue. It was suggested by an in vivo study that carnitine
      pretreatment prevented the subclinic bronchospasm in children who underwent
      chronic hemodialysis. Tracheal and lung parenchymal preparations of 10 guinea
      pigs and 5 human bronchial tissues were prepared and mounted in 20-mL organ
      baths. In the first series of experiments, contractions to carbachol and
      histamine (10(-9) to 10(-3) M) were compared after the tissues were incubated
      with different concentrations of L-carnitine (10(-6) to 10(-4) M). pD(2) values
      were compared with analysis of variance (ANOVA) and P <.05 was considered as
      significant. In the second part of experiments, the inhibitory effect of L
      carnitine (10(-9) to 10(-3) M) was investigated on the sustained contractions of
      preparations to carbachol (10(-6) M) and histamine (10(-5) M). In the first part
      of the study pD(2) values obtained with carbachol were 6.48 +/- 0.09, 5.42 +/-
      0.05, and 6.48 +/- 0.02 for guinea pig trachea, guinea pig lung parenchymal
      strips, and human bronchial tissues, respectively. pD(2) values obtained with
      histamine were 5.34 +/- 0.10, 5.74 +/- 0.06, and 6.32 +/- 0.03 for guinea pig
      trachea, guinea pig lung parenchymal strips, and human bronchial tissues,
      respectively. No significant difference was observed between the pD(2) values
      before and after incubation with carnitine (P >.05). In the second part of the
      study, only 10(-4) M L-carnitine exerted an insignificant relaxant effect (6.16%
      +/- 1.22% on carbachol induced contractions and 4.48% +/- 0.85% on histamine
      induced contractions) in guinea pig trachea. Our results show that L-carnitine
      exerts no in vitro relaxant effect in guinea pig trachea, guinea pig lung
      parenchymal strips, and human bronchial preparations.

PMID- 12217215
TI  - Long-term inhalation of diesel exhaust affects cytokine expression in murine lung
      tissues: comparison between low- and high-dose diesel exhaust exposure.
AB  - The authors investigated the effect of diesel exhaust (DE) on cytokine expression
      in murine lung tissues. BALB/c mice were exposed to DE for 1 month at different
      dose levels of DE (low dose: diesel exhaust particles [DEP] 100 micro g/m(3);
      high dose: 3mg/m(3)). After exposure, the authors examined mRNA expression of
      cytokines (tumor nocrosis factor alpha [TFN-alpha], Interleukin [IL]-1beta, IL-4,
      IL-6, IL-10, IL-12p40, and interferon gamma [IFN-gamma] and inducible nitric
      oxide synthase (iNOS) in the lung, and also measured the secretion of TNF-alpha
      and IL-10 protein by alveolar macrophages (AM). The mRNA expression levels of
      inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-12p40, IFN-gamma) and iNOS,
      which are important for host defense, were suppressed significantly. However, the
      IL-10 mRNA level was increased by DE exposure. The IL-4 mRNA level was increased
      by low-dose DE exposure but suppressed by high-dose DE exposure. TNF-alpha and IL
      10 secretion by AM paralleled mRNA expression. Chronic inhalation of DE affects
      cytokine expression in murine lung. These results suggest that DE alters
      immunological responses in the lung and may increase susceptibility to pathogens,
      and that increased IL-4 expression by low-dose DE exposure may induce allergic
      reaction such as asthma.

PMID- 12217217
TI  - Intratracheal instillation of perfluorocarbon rescued mice with primary pulmonary
      hypoplasia.
AB  - The aim of this study was to investigate the effect of perfluorocarbon on the
      respiratory status of newborn mice with pulmonary hypoplasia without
      diaphragmatic defects, following intrauterine exposure to nitrofen. Three groups
      of newborn mice were compared: pups exposed to nitrofen antenatally without
      (group A) or with (group B) perfluorocarbon treatment and pups not exposed to
      nitrofen as a control (group C). Respiratory evaluation was performed by scoring,
      pressure-volume analysis, and histological examination. At 40 minutes after
      birth, the survival rates in groups A, B, and C were 51%, 94%, and 95%,
      respectively. The clinical scores of group B mice at 40 minutes were
      significantly better than those of group A mice in which pulmonary hypoplasia was
      induced. In group B, the hysteresis ratio was significantly higher than that in
      group A, and lung histology showed a significant increase in airspace. An
      immunohistochemical examination showed that perfluorocarbon did not alter the
      expression of mature surfactant protein B and surfactant proprotein C. This study
      demonstrated that treatment with perfluorocarbon was useful in stabilizing
      critically ill mice with primary pulmonary hypoplasia during the early phase of
      therapy.

PMID- 12217216
TI  - Lung pathology in platelet-derived growth factor transgenic mice: effects of
      genetic background and fibrogenic agents.
AB  - We previously developed transgenic mice expressing human platelet-derived growth
      factor B chain (PDGF-B) from the lung-specific surfactant protein C (SPC)
      promoter. These mice developed enlarged airspaces, inflammation, and fibrosis of
      varying severity. In the present study we examined potential causes of this
      phenotypic variation and tested whether constitutive PDGF-B expression
      exacerbated fibrosis induced by bleomycin and silica. The SPC-PDGFB transgene
      construct was modified by replacement of the PDGF-B 3' UTR, which contains motifs
      known to mediate instability in other cytokine genes, with SV40 sequences
      containing an intron and polyadenylation signal. This modification resulted in an
      increase in the efficiency with which the construct was expressed, but no
      difference in lung pathology was observed compared to the original construct.
      Backcrossing of mice carrying the original SPC-PDGFB construct to C57BL/6 and SJL
      inbred strains resulted in a more severe phenotype in SJL-bred mice compared to
      C57BL/6-bred mice after 4 generations. To determine whether SPC-PDGFB transgenic
      mice had increased susceptibility to fibrogenic agents, the mice were treated
      with bleomycin or silica. No significant differences were detected in lung
      weight, hydroxyproline content, or histopathologic changes between transgenic and
      wild-type mice after bleomycin or silica treatment. These results demonstrate
      that the amount of PDGF-BB produced in wild-type mice is not a limiting factor in
      the development of bleomycin- or silica-induced pulmonary fibrosis.

PMID- 12217220
TI  - Effects of a long-term psychosocial nursing intervention on adolescents exposed
      to catastrophic stress.
AB  - This research tested the effects of a long-term psychosocial nursing intervention
      designed to decrease mental distress in adolescents following a catastrophic
      event. Advanced Practice Psychiatric Nurses conducted the Catastrophic Stress
      Intervention (CSI) in two South Carolina high schools for three years following
      Hurricane Hugo. The CSI consisted of nine protocols designed to decrease
      adolescents' mental distress by increasing their understanding of stress and by
      enhancing their self-efficacy and social support. Adolescents (N = 1030) were
      randomized to intervention or control groups and completed one baseline and five
      postintervention measures of mental distress, self-efficacy, and social support.
      The hypothesis was that intervention adolescents would have less mental distress
      than control adolescents. The research also addressed the particular time points
      at which differences between intervention and control adolescents might be shown.
      Repeated measures multivariate analysis of variance, with exposure to the
      hurricane, self-efficacy, and social support as control variables, showed that
      intervention adolescents reported less mental distress than control adolescents
      at 12, 18, and 24 months but that this difference dissipated by 30 and 36 months.
      Implications for the CSI and timing of interventions with adolescents after a
      catastrophic event are discussed.

PMID- 12217221
TI  - A decision tree and clinical paths for the assessment and management of children
      with ADHD.
AB  - Attention Deficit/Hyperactivity Disorder (ADHD) is a common neurobehavioral
      disorder. Children with ADHD are disproportionately represented in pediatric
      populations characterized by school failure, criminal behavior, and substance
      abuse. Many children who present with ADHD symptomatology do not receive
      systematic assessments nor comprehensive treatment that is well coordinated
      across home and school environments. And yet, evidence suggests that early
      detection and appropriate treatment can alter the probability of a negative
      developmental trajectory. The Decision Tree and Clinical Paths for Assessment and
      Management of ADHD identify the critical components of care through a stepwise
      decision-making process involving the assessment, diagnosis, treatment, and
      outcome evaluation of children who present with ADHD symptomatology. Preliminary
      field testing supports the clinical utility and validity of the ADHD Decision
      Tree/Paths. In addition, cross-validation comparisons indicate consistency
      between the ADHD Decision Tree/Paths and recently released ADHD clinical
      guidelines issued by several national professional organizations.

PMID- 12217222
TI  - The experience of major depression: adolescents' perspectives.
AB  - Approximately 70% of adolescents with major depression are not receiving adequate
      assessment and treatment due, in part, to an incomplete picture of the disorder.
      Current conceptualizations of depression in adolescence have not adequately
      addressed integration of developmental principles, salient contextual events, and
      the adolescent viewpoint of precipitators, symptoms, and treatments. The purpose
      of this study was to describe the experience of major depression from the
      adolescent's perspective to provide a more comprehensive description of the
      disorder. Using a phenomenologic approach, in-depth interviews were conducted
      with five depressed adolescents, ages 13-17. Data analysis, using an adaptation
      of Colaizzi's method, resulted in eight theme categories. The essential structure
      of the experience was formulated from all data. Adolescents focused on anger,
      fatigue, and interpersonal difficulties as characteristic of depression. The
      results call for increased awareness of the unique aspects of adolescents, an
      examination of adolescent-accessible services, and further clarification of the
      roles of friends and siblings in the disorder.

PMID- 12217223
TI  - Equine-facilitated group psychotherapy: applications for therapeutic vaulting.
AB  - In this day of high-tech, managed-care service delivery with an emphasis on
      medication and brief treatment, it is important for nurses to be aware of
      nontraditional treatment options that may be uniquely beneficial for some
      clients. Although it may still be considered a novelty, including animals in the
      healing milieu is not a new idea. Florence Nightingale herself suggested that "a
      small pet animal is often an excellent companion for the sick, for long chronic
      cases especially" (Nightingale, 1969, p. 102). Healing, according to one recent
      nursing article, can be seen as "a gradual awakening to a deeper sense of the
      self (and of the self in relation to others) in a way that effects profound
      change" (Dorsey & Dorsey, 1998, p. 36). Equine-facilitated psychotherapy, while
      not a new idea, is a little-known experiential intervention that offers the
      opportunity to achieve this type of awakening. In this article, the reader is
      introduced to equine-facilitated psychotherapy's theoretical underpinnings,
      techniques, and outcomes as illustrated by actual clinical vignettes and research
      findings.

PMID- 12217224
TI  - Asperger's syndrome: implications for nursing practice.
AB  - The most common disorders within the category of Pervasive Developmental
      Disorders (PDD) are the Autistic Disorders. In the 1994 Diagnostic and
      Statistical Manual-IV, Asperger's Disorder became a distinct diagnosis within the
      Autistic category, as part of the disorders first diagnosed in childhood and
      adolescence. The terms Asperger's Disorder and Asperger's Syndrome are used
      interchangeably. Attention to and knowledge of Asperger's Syndrome (AS) are
      necessary to differentiate it from closely related disorders that have
      overlapping symptoms. There is much discussion about different definitions of
      Asperger's, different viewpoints of experts in the field, and the diagnostic
      dilemmas related thereto. Last, and most important, are the nursing implications.
      Nurses are in a position to identify children with Asperger's early. After
      identification, the necessary referrals, treatment options, support, and follow
      up are essential for these children. Nurses need more knowledge about this
      disorder and need to be proactive in defining their role to help children with
      the disorder in the schools and the community.

PMID- 12217225
TI  - What parents of mentally ill children need and want from mental health
      professionals.
AB  - Child psychiatric hospitalization is a time of crisis for the parents of a child
      with a mental disorder. Prior to hospitalization, the child's problematic
      behavior has escalated. Parents have various types of contact with mental health
      professionals prior to, during, and after the hospitalization, which influence
      their ability to care for their child. This paper reports a qualitative
      descriptive study of what parents need and want from mental health professionals
      during this time frame. During the study, parents spontaneously talked about what
      they needed and wanted from mental health professionals, including nursing
      personnel. The perspectives of 38 parents of 29 hospitalized children were
      obtained through interviews. Parents identified needing informational, emotional,
      and instrumental support most often in the interviews. Specific examples from the
      data are included in this report.

PMID- 12217226
TI  - The challenge of providing continuity in the care of a disabled child: Smith
      Lemli-Opitz syndrome.
AB  - The health of a disabled child can be adversely affected if parents and health
      care providers are not informed regarding the need for ongoing care and
      consultation. This case illustrates the ways in which failure to obtain
      appropriate consultation and breakdown in communication between parents, health
      care providers, and community agencies negatively impacted the health of a young
      child with Smith-Lemli-Opitz Syndrome (SLOS). Although the disorder was detected
      in the child, information regarding treatment was not communicated to those
      caring for the child, resulting in serious and potentially life-threatening
      consequences. In this case study, we review the pathophysiology of SLOS, the
      positive impact of making use of expert consultation, and the complexities of
      navigating multiple systems when advocating for a child with a serious
      developmental disorder. The role of nursing in facilitating collaboration among
      families, members of the health care team, and advocacy agencies, particularly in
      children with complex medical and psychiatric difficulties, is highlighted.

PMID- 12217227
TI  - Maternal expressed emotion as a predictor of emotional and behavioral problems in
      low birth weight children.
AB  - The purpose of this study was to determine the degree to which maternal emotions
      expressed toward low birth weight infants (<2500 gm) at six months of age
      predicted emotional and behavioral problems at two years of age. With a sample of
      83 mother-infant dyads, a Revised Five Minute Speech Sample (R-FMSS) was used to
      measure the Expressed Emotion (EE) constructs of Negative EE (criticism,
      hostility), Positive EE (positive remarks, warmth) and Overinvolved EE. Problem
      behaviors were measured at two years of the child's age utilizing the Child
      Behavior Checklist/2-3. Infant temperament was controlled for using the Revised
      Infant Temperament Questionnaire. While temperament contributed the most variance
      to the development of emotional and behavioral problems, results indicated that
      Negative EE was a significant predictor of internalizing problems such as anxiety
      and withdrawal. The detrimental impact of Negative EE was most substantial for
      infants who adapted less readily to the demands of their environments and who had
      more difficulty persisting with a task or activity. Although Positive EE did not
      influence the incidence of problems for children in general, it did appear to
      reduce the likelihood of developing internalizing problems for more persistent
      children. Overinvolved EE showed no relationship to the incidence of problems
      reported for a child. Nurses are in the prime position to identify negative
      maternal-infant interactions during the first year of life that may place the low
      birth weight infant at risk for poor mental health outcomes.

PMID- 12217228
TI  - Using posturography to detect unsteadiness in 13 patients with peripheral
      neuropathy: a pilot study.
AB  - Our aims were to use posturography to see if sway pattern differed between
      patients with large-fiber peripheral neuropathy and normal control subjects and,
      if it did, to compare posturography with conventional electromyography (EMG) as
      screening tools for large-fiber peripheral neuropathy. Thirteen patients who came
      to our neurophysiology laboratory with a preliminary diagnosis of peripheral
      neuropathy (made by their referring physicians) were compared with 7 nonmatched
      control subjects. All subjects received a neurologic examination and underwent
      posturography and conventional EMG. Results of posturography and conventional EMG
      were compared. Posturography showed abnormal sway patterns only in patients who
      had EMG abnormalities consistent with large-fiber peripheral neuropathy. These
      sway patterns differed significantly from those of the control subjects.
      Posturography seems to be a useful and well-tolerated screening test for patients
      with a history suggestive of peripheral neuropathy, and results of posturography
      agree with those of conventional EMG. Moreover, posturography directly measures
      increased sway in these patients and may be used as a more direct screen for risk
      of falls in this population.

PMID- 12217229
TI  - Vaginal sonography of the cervix for the prediction of "time to delivery" in ART
      twins gestations.
AB  - The present study aimed to determine a reliable tool to estimate the interval
      time to delivery in assisted conception twin pregnancies. Mid-gestation cervical
      length was prospectively measured using transvaginal sonography (TVS) during
      routine antenatal care. Fifty-seven of 101 suitable women were longitudinally
      followed and two TVS measurements of their cervical length were obtained, first
      at approximately 24 weeks gestation and then at approximately 27 weeks gestation.
      The mean cervical length decreased from 37 +/- 12mm at first measurement to 34 +/
      11mm at the second one. A linear regression model was found between the time
      interval of the first (R = 0.656, p < 0.001) and the second (R = 0.435, p <
      0.001) assessments and the week of delivery. The current data confirm that the
      length of the preserved segment of the cervix is an important indicator of its
      competence. A simple equation using the cervical length (mm) divided by 3 can
      predict mid gestation scan-to-delivery interval in twin gestation.

PMID- 12217230
TI  - Perinatal mortality in term and preterm twin and singleton births.
AB  - Although, in general, twins have higher perinatal mortality rates than
      singletons, preterm twins have lower perinatal mortality rates than singletons of
      the same birth weight or gestational age. This study investigated the hypotheses
      that this paradoxical twin advantage: 1) is due to gestational age distribution
      differences between the singleton and twin populations, and 2) is due to
      increased likelihood of birth having occurred in a tertiary perinatal center. A
      pre-existing, time-limited data set of all births in the province of Ontario in
      odd years between 1979 and 1985 was chosen for this study because of the large
      sample size (n = 618,579). Multivariable logistic regression of the relationship
      between perinatal mortality and twin status was controlled for mother's age,
      hospital level and gestational age. Findings confirm the lower mortality of
      preterm twins. After controlling for level of hospital of birth this difference
      remained, suggesting that level of hospital of birth was not a major factor
      responsible for the twin advantage. Analyses in which gestational age was
      standardized indicate that, for those whose gestational age was less than 2 SD
      below the mean for their particular group (twin or singleton), twins were
      actually at higher risk than singletons. These results support hypothesis 1 and
      do not strongly support hypothesis 2. The results also support earlier authors'
      suggestions that the definition of term birth should be different for twins and
      singletons

PMID- 12217231
TI  - Twin and singleton births in Ghana--a case-control study.
AB  - A retrospective study involving 623 twin and 1246 singleton births was conducted
      to compare the two groups with regard to selected maternal, fetal and labor and
      delivery characteristics and outcomes. Maternal age and parity were significantly
      higher for twins. The risks of preterm delivery, arrival in the labor ward in
      second stage of labor, cesarean births and postpartum haemorrhage were
      significantly higher in twin than in singleton births. In vaginal deliveries twin
      mothers were significantly less likely to have had episiotomies or perineal
      lacerations. There was no difference in the duration of the third stage of labor
      or in the incidence of retained placentae. Antepartum haemorrhage was a less
      likely indication for cesarean delivery among twins, while there was no
      significant difference in the likelihood of severe pre-eclampsia/eclampsia being
      an indication. Singleton babies were significantly heavier than twins. The
      incidences of malpresentation, low birth weight, stillbirths and of admission of
      live births to the neonatal intensive care unit were significantly higher in
      twins. There was no difference in the rate of instrumental vaginal delivery, or
      in the route of delivery of fetuses presenting by the breech. There is the need
      for detailed study of the incidences of antepartum haemorrhage and hypertensive
      diseases in twin and singleton pregnancies and of the factors determining the
      mode of delivery when such complications arise. Labor and delivery should also be
      examined to determine any differences between the two groups, especially in the
      first and second stages.

PMID- 12217232
TI  - Errors in birth registrations and coding of twins and higher order multiples.
AB  - Dizygotic compared with monozygotic conceptions are at decreased risk of fetal
      and infant death and serious morbidity in surviving infants. Different sex twin
      maternities must be dizygotic but miscoding and incorrect registration of sex and
      number of fetuses may lead to an incorrect assignment of zygosity. The aim of the
      study was to validate the coding and registration of number and sex of births in
      multiple pregnancies. Fetal and infant death registrations from all multiple
      maternities in England and Wales 1993-1998 were examined. There were 51,792 twin,
      1627 triplet and 51 higher order multiple maternities that were registered. Among
      these there were 1926 fetal deaths, 58 of which were registered as being of
      indeterminate sex but were coded as male in 56 and female in 2 cases. A fetus
      papyraceous was registered as male in 19 and as female in 19 cases. Other fetal
      deaths weighing >/= 100g, with no mention of papyraceous on the death
      certificate, nevertheless, likely to be of indeterminate sex, were registered as
      male in 26 and as female in 23 cases. In 13 maternities, the number of infants
      registered at birth was less than the number mentioned on the registration
      certificate. It cannot be assumed that multiple births of different registered
      sex are dizygotic. As surviving infants from a monozygotic multiple birth are at
      much greater risk of infant death and serious morbidity than dizygotic multiple
      births, incorrect assignment of sex has important implications for parental
      counselling and may have medico-legal relevance when attributing negligence as
      the cause of morbidity in a survivor from a multiple pregnancy.

PMID- 12217233
TI  - A comparison of educational achievement in a national sample of Dutch female
      twins and their matched singleton controls.
AB  - The aim of this study was to compare the educational achievement of female twins
      (n = 577) and their matched singleton controls (n = 447), who were selected from
      participants of a national test of educational achievement in the years 1993 to
      1998. To assure the representativeness of the selected groups we also compared
      the achievement scores of the twins and the controls to those of the total Dutch
      female population tested in the same period. We analyzed the results of the
      following educational achievement scales: Language, Mathematics and Information
      Processing. The results indicated that the singleton classmates performed
      significantly better than the twins on all three scales. However, the twins
      performed equally well as compared to the Dutch female population. We believe
      that our singleton control group was not as properly selected as we intended, a
      selection bias operative at the level of the schools may have confounded the
      comparison. We therefore conclude on the basis of a comparison with the
      performance of the total Dutch female population that there are no differences in
      educational achievement between female twins and singletons.

PMID- 12217234
TI  - Genetic and environmental influences on expression of recurrent headache as a
      function of the reporting age in twins.
AB  - To explore age-related mechanisms in the expression of recurrent headache, we
      evaluated whether genetic and environmental influences are a function of the
      reporting age using questionnaire information that was gathered in 1973 for 15-
      to 47-year-old Swedish twins (n = 12,606 twin pairs). Liability to mixed headache
      (mild migraine and tension-type headache) was explained by non-additive genetic
      influences (49%) in men aged from 15 to 30 years and additive genetic plus shared
      environmental influences (28%) in men aged from 31 to 47 years. In women, the
      explained proportion of variance, which was mainly due to additive genetic
      effects, ranged from 61% in adolescent twins to 12% in twins aged from 41 to 47
      years, whereas individual specific environmental variance was significantly lower
      in twins aged from 15 to 20 years than in twins aged from 21 to 30 years.
      Liability to migrainous headache (more severe migraine) was explained by non
      additive genetic influences in men, 32% in young men and 45% in old men, while
      total phenotypic variance was significantly lower in young men than in old men.
      In women, the explained proportion of variance ranged from 91% in the youngest
      age group to 37% in the oldest age group, with major contributions from non
      additive effects in young and old women (15-20 years and 41-47 years,
      respectively) and additive genetic effects in intermediate age groups (21-40
      years). While total variance showed a positive age trend, genetic variance tended
      to be stable across age groups, whereas individual specific environmental
      variance was significantly lower in adolescent women as compared to older women.

PMID- 12217236
TI  - Analysis of functional abilities for elderly Danish twins using GEE models.
AB  - In this work we present a new method for genetic analysis of twin data which is
      based on generalized estimating equations and allows for analysis of various
      response types (e.g., continuous, binary, counts) combined with estimation of
      residual correlations. The new approach allows for control of covariates of any
      kind (e.g., continuous, counts) by modeling the dependence of mean and variance
      on background variables. The proposed method was applied to identify the
      covariates that have a significant influence on elderly people's functional
      abilities, and find the estimates for the correlation coefficients of residuals
      for MZ and DZ twins in a sample of 2401 Danish twin 75 years of age or older. The
      bootstrap method was used to obtain standard errors for correlation coefficients.
      It was shown, that the chosen covariates have similar effects on MZ and DZ twins,
      and that the residual correlation in MZ twins is significantly higher than in DZ
      twins, which indicates that genetic factors play an etiological role in the
      determination of physical status of elderly people, controlled for 10 background
      variables.

PMID- 12217235
TI  - HLA haplotypes in dizygotic twin pairs: are dizygotic twins more similar than
      sibs?
AB  - It has been suggested that dizygotic twin pairs share two HLA haplotypes more
      often than ordinary siblings and thus might be genetically more alike. We tested
      this hypothesis in dizygotic twin pairs from the Danish Twin Registry. A total of
      114 (60 female and 54 male) same-sexed healthy twin pairs aged 18-45 years
      participated. Dizygosity was established by means of DNA sequencing of nine
      polymorphic markers. HLA-A, B and Cw specificities were typed with serology, and
      if data were inconclusive, with DNA typing. If twin partners had the same HLA
      types, they were assumed to share two haplotypes. If they had 1 HLA A, B and C
      antigen group in common they were assumed to share one haplotype and if they had
      no HLA types in common they were assumed to share zero haplotypes. Since HLA
      types from parents were unavailable we could not test for identity-by-descent and
      thus had a risk of overestimating the number of twins sharing two haplotypes. A
      Chi-square test was used to compare observed numbers in each haplotype sharing
      group with the expected numbers. Twenty-nine (expected 28.5) twin pairs had two
      HLA-types in common, 52 (expected 57) had one HLA-type in common and 33 (expected
      28.5) had zero HLA-types in common, p = 0.56. Our data show that DZ twins are not
      more similar than sibs from different pregnancies in general.

PMID- 12217237
TI  - Paternally derived twinning: a two century examination of records of one Scottish
      name.
AB  - Paternal influence on twinning was investigated through a study of all the state
      and church records of Scotland for the period 1800-2000 (nine generations) in
      relation to one Scottish patronymic - in total 50,000 births. All recorded twins
      born with the chosen patronymic were identified and their whole paternal ascent
      and descent on the male line were charted for twins. There were established three
      pedigrees A, B and C manifesting clear paternal twinning hereditary transmission.
      Detailed familial reproduction patterns were traced for pedigree A, including
      phenotypic identification of twin zygosity in relation to seven same sexed pairs
      of twins in the pedigree and one same sexed pair out of dizygotic triplets. It is
      the most comprehensive description to date of such a kind of twin familial trait.
      The data presented show (i) the unique feature of clear direct paternal influence
      on twinning in three families; (ii) paternal factor(s) determination in both DZ
      and MZ twinning; and (iii) a definite association of twinning tendency with a
      partial male infertility, which corresponds to the prediction of the
      Infertility/Twinning Paternally Dependent syndrome hypothesis. The hypothesis of
      a founder effect explaining the similarity of A, B, C families and the possible
      localisation of the paternally dependent twinning factor on the Y-chromosome are
      currently under molecular investigation.

PMID- 12217238
TI  - The case for the odd case.

PMID- 12217239
TI  - Exercise therapy in patients with rheumatoid arthritis.

PMID- 12217240
TI  - Recurrent pregnancy loss with the antiphospholipid antibody: a systematic review
      of therapeutic trials.

PMID- 12217241
TI  - The relation between antiphospholipid syndrome-related pregnancy morbidity and
      non-gravid vascular thrombosis: a review of the literature and management
      strategies.
AB  - The antiphospholipid syndrome (APS) is associated with pregnancy morbidity and
      vascular thrombosis in the presence of circulating antiphospholipid (aPL)
      antibodies. Clinical manifestations of aPL antibodies represent a spectrum
      (asymptomatic, pregnancy events, vascular events, or both pregnancy and vascular
      events), and APS should not be considered a single disease with a predictable
      outcome. Patients with aPL antibodies are at increased risk of vascular
      thrombotic events during pregnancy, the postpartum period, and even during long
      term follow-up after an APS-related pregnancy event. Therefore, the purpose of
      this paper is to review the relation between APS-related pregnancy morbidity and
      vascular thrombosis, and to address the importance of prophylactic therapy during
      and after APS pregnancies to prevent maternal thrombotic complications. During
      pregnancy, low-dose aspirin (LDA) should be considered for all patients with aPL
      antibodies and heparin should be added to LDA in patients fulfilling the Sapporo
      criteria for definite APS. During delivery, especially with caesarian section,
      periods without anticoagulation should be kept to an absolute minimum. Some data
      suggest that LDA might be effective against future non-gravid vascular thrombosis
      in patients with APS and a history of only pregnancy morbidity.

PMID- 12217242
TI  - Antiphospholipid antibodies in pediatrics.
AB  - Antiphospholipid antibody syndrome has been associated with vascular thrombosis,
      thrombocytopenia, hemolytic anemia, livedo reticularis, neurologic disorders, and
      recurrent fetal loss. The diagnosis of antiphospholipid syndrome is given in the
      presence of an elevated anticardiolipin antibody lupus anticoagulant in addition
      to a thrombotic event. Antiphospholipid antibodies are responsible for a majority
      of thrombotic events in children. These antibodies can present as a primary
      syndrome or secondary to other diseases, such as systemic lupus erythematosus.
      Anticoagulation therapy with heparin and low-dose aspirin is the recommended
      treatment in pediatric patients.

PMID- 12217244
TI  - Cyclosporin A and intravenous immunoglobulin treatment in
      polymyositis/dermatomyositis.

PMID- 12217243
TI  - Treatment and monitoring of patients with antiphospholipid antibodies and
      thrombotic history (Hughes syndrome).
AB  - Patients with Hughes (antiphospholipid) syndrome who develop an initial
      thrombosis have an increased risk of subsequent thrombotic events. Current
      therapy to prevent recurrent thrombosis is controversial. While it seems clear
      that anticoagulant treatment is a better option than anti-aggregants alone, there
      is no consensus regarding the duration and intensity of oral anticoagulation. The
      risk of bleeding, the main complication of anticoagulant treatment, and the need
      for frequent monitoring of the International Normalized Ratio to measure the
      anticoagulant effect of warfarin concern patients and physicians. In addition,
      there is some debate about the validity of the International Normalized Ratio in
      patients with lupus anticoagulant activity. The development of new therapies that
      target more specific pathogenic mechanisms is highly warranted.

PMID- 12217245
TI  - Critical illness myopathy.
AB  - Acute myopathy is a common problem in intensive care units. Those at highest risk
      for developing critical illness myopathy are exposed to intravenous
      corticosteroids and paralytic agents during treatment of various illnesses.
      Diffuse weakness and failure to wean from mechanical ventilation are the most
      common clinical manifestations. Serum creatine kinase levels are variable.
      Electrodiagnostic studies reveal findings of a myopathic process, often with
      evidence of muscle membrane inexcitability. Based on animal model studies, the
      loss of muscle membrane excitability may be related to inactivation of sodium
      channels at the resting potential. In addition, human and animal pathologic
      studies reveal characteristic loss of myosin with relative preservation of other
      structural proteins. In some patients, there is also upregulation of proteolytic
      pathways, involving calpain and ubiquitin, in conjunction with increased
      apoptosis. Fortunately, the disorder is reversible, but there may be considerable
      morbidity.

PMID- 12217246
TI  - Pulmonary complications of inflammatory myopathy.
AB  - Pulmonary manifestations contribute significantly to the morbidity and mortality
      of the idiopathic inflammatory myopathies, ranging from intrinsic lung disease to
      secondary complications that include aspiration pneumonia, opportunistic
      infection, congestive heart failure, and hypoventilation. Newer classification
      schemes for interstitial lung disease have permitted closer correlation between
      histologic subtype and clinical outcome, while diagnostic techniques such as
      bronchoalveolar lavage have begun to define the cellular elements responsible for
      immune-mediated pulmonary dysfunction. Investigators have identified several
      serum markers correlating with inflammatory disease activity in the lung that
      should enhance noninvasive monitoring of therapeutic responses to newer regimens
      involving agents such as cyclosporine and tacrolimus. Taken together, these
      advances have contributed to better understanding of the immunopathogenesis of
      myositis-associated interstitial lung disease that should ultimately translate
      into more effective treatment.

PMID- 12217247
TI  - Malignancy in patients with inflammatory myopathy.
AB  - The most recent evidence from population-based cohort studies confirms the
      association between malignancy and dermatomyositis and polymyositis. These
      studies show an even stronger association between polymyositis and malignancy
      than previous studies, suggesting less misclassification. This is particularly
      true of one study that used pathologic criteria to distinguish between myositis
      subtypes. Recent data also confirm that the association for dermatomyositis and
      polymyositis is not purely caused by diagnostic suspicion or surveillance bias.
      More data are still required to determine individual cancer risks, although it
      appears that ovarian and lung cancer are associated with dermatomyositis while
      lung cancer and non-Hodgkin's lymphoma are associated with polymyositis. An
      association between malignant disease and inclusion body myositis has also been
      verified for the first time. Of interest, too, is the increasing number of
      reports documenting cases in which the clinical course of the myositis mirrors
      that of the cancer, supporting the notion that in some instances, myositis is a
      paraneoplastic disorder.

PMID- 12217248
TI  - Newest pathogenetic considerations in inclusion-body myositis: possible role of
      amyloid-beta, cholesterol, relation to aging and to Alzheimer's disease.
AB  - This report summarizes clinical features and diagnostic criteria, and the newest
      advances related to seeking the pathogenic mechanism(s) of sporadic inclusion
      body myositis. On the basis of the authors' research, several processes seem to
      be important in relation to the still-speculative pathogenesis: increased
      transcription and accumulation of amyloid-b precursor protein and accumulation of
      its proteolytic fragment amyloid-b; abnormal accumulation of components related
      to lipid metabolism (eg, low-density lipoprotein receptors and cholesterol;
      accumulation of cholesterol is possibly caused by its abnormal trafficking);
      oxidative stress; accumulations of other Alzheimer-related proteins including
      phosphorylated tau; a milieu of muscle cellular aging in which these changes
      occur. The authors' basic hypothesis is that overexpression of amyloid-b
      precursor protein within the aging muscle fibers is an early upstream event
      causing the subsequent pathogenic cascade. The remarkable pathologic similarities
      between inclusion-body myositis muscle and Alzheimer's disease brain are
      discussed.

PMID- 12217249
TI  - Idiopathic inflammatory myopathy: autoantibody update.
AB  - Several defined, specific autoantibodies have been associated with polymyositis
      and dermatomyositis. These include autoantibodies to at least six of the
      aminoacyl-transfer-ribonucleic-acid synthetases; to the signal recognition
      particle; to the protein complexes labeled Mi-2 and PM-Scl; and several
      autoantibodies, such as anti-U1nRNP and anti-Ro/SSA, that have recognized
      associations with other conditions. These autoantibodies are a continuing area of
      interest. Recent studies have involved the clinical implications of these
      autoantibodies, and their potential significance for etiology and pathogenesis of
      the disease. This report will review recent studies of myositis autoantibodies
      and their clinical associations, both extramuscular features, such as
      interstitial lung disease and aspects of the myositis itself. New myositis
      autoantibodies continue to emerge, which may have clinical utility. Several have
      been associated with dermatomyositis, including juvenile dermatomyositis, which
      has a low frequency of traditional myositis autoantibodies. There is also new
      information regarding the antigenic targets of anti-Mi-2 and anti-PM-Scl, two of
      the earliest recognized myositis autoantibodies. New evidence over the past few
      years has challenged old concepts of the relationship of autoantibodies to the
      pathogenesis of myositis, and has suggested potential new mechanisms for the
      origin of the associated autoantibodies. Despite this progress, the reason for
      production of the autoantibodies and their role in tissue injury remain unknown.

PMID- 12217250
TI  - Opportunities for cardiovascular risk reduction with angiotensin II receptor
      blockers.

PMID- 12217251
TI  - Evolving strategies for the use of combination therapy in hypertension.
AB  - Two thirds of patients with hypertension require more than one drug to achieve
      goal blood pressure. Rational antihypertensive drug combinations are based on
      their ability to produce additive blood pressure reduction and reduce the
      incidence of dose-dependent side effects. Some combinations exhibit side-effect
      neutralization in which side effects associated with one drug are neutralized by
      a second agent. Fixed-dose combinations improve adherence by reducing the number
      of pills and simplifying the treatment regimen. Because volume overload is
      common, low-dose diuretics are often included in drug combinations. Combinations
      of diuretics with potassium-sparing diuretics, angiotensin converting enzyme
      inhibitors, angiotensin receptor blockers, and b-blockers are useful in treating
      large segments of the hypertensive population. Combinations of calcium channel
      blockers and angiotensin converting enzyme inhibitors are also effective and
      reduce the incidence of calcium blocker-related edema. Combinations of agents
      affecting the renin-angiotensin system by different mechanisms are currently the
      subject of active investigation.

PMID- 12217252
TI  - Managing the hypertensive patient with ischemic heart disease.
AB  - Thiazide diuretics, b-blockers, calcium channel blockers, and angiotensin
      converting enzyme (ACE) inhibitors are all superior to placebo for the primary
      prevention of coronary events in patients with hypertension. Recent studies have
      shown that ACE inhibitors are better than other antihypertensive agents in
      lowering overall cardiovascular morbidity and mortality, especially stroke. Blood
      pressure should be aggressively lowered (to < 140/90 mm Hg), especially in
      diabetic patients (to < 130/80 mm Hg), but care should be exercised in lowering
      the diastolic blood pressure below 65 mm Hg in patients with significant
      occlusive coronary artery disease. Hypertension in patients with stable angina
      should be treated with a b-blocker (alternatively a calcium channel blocker)
      together with an ACE inhibitor. Patients with hypertension and acute coronary
      syndrome (unstable angina or myocardial infarction) should be treated with a b
      blocker, and with an ACE inhibitor if there is left ventricular dysfunction. A
      thiazide diuretic and/or a dihydropyridine calcium channel blocker could be added
      for blood pressure control. Calcium channel blockers should be avoided if there
      is significant left ventricular dysfunction.

PMID- 12217253
TI  - Optimizing blood pressure control in the obese patient.
AB  - Obesity is a major public health issue, and hypertension is one of the most
      common associated comorbidities. Current guidelines for optimal blood pressure
      levels in obese patients or for the treatment of obesity-hypertension do not
      provide specific recommendations that go beyond the rather general recommendation
      to lose weight. Based on the strong ties between obesity, hypertension, and type
      2 diabetes, and the similarity of complications that occur in obesity-related
      hypertension and in hypertension associated with type 2 diabetes, it seems
      appropriate to explore the optimal blood pressure levels for obese hypertensive
      patients. Recently published studies underline the importance of weight reduction
      to reach this goal. Several lines of reasoning support the use of angiotensin
      converting enzyme inhibitors or angiotensin receptor blockers as the appropriate
      first-line therapy in obese patients with uncomplicated hypertension.
      Nondihydropyridine calcium channel blockers, a-blockers, or low-dose diuretics
      may be added when necessary. Clearly, further studies are needed to define target
      blood pressure levels in obese patients and to clarify the value of established
      and newer drugs, like angiotensin receptor blockers, for the treatment of obese
      hypertensive patients. The role of antiobesity drugs in the management of the
      obese hypertensive patient also remains to be defined.

PMID- 12217254
TI  - Renal dysfunction as a cardiovascular risk factor.
AB  - Indices of altered renal function (eg, microalbuminuria, increased serum
      creatinine concentration, or decrease in estimated creatinine clearance,
      particularly overt proteinuria) are independent predictors of cardiovascular
      morbidity and mortality. These parameters should be routinely evaluated in the
      elderly and in high cardiovascular risk populations, particularly when
      hypertension is present. Hypertensive kidney damage should be prevented by early
      aggressive treatment of hypertensive patients with microalbuminuria. To avoid
      further aggravation of high cardiovascular risk, antihypertensive agents devoid
      of unwanted metabolic side effects should be used. Epidemiologic information
      suggests that renal and cardiovascular outcome run parallel in this segment of
      the population.

PMID- 12217255
TI  - Ambulatory blood pressure measurement in the renal patient.
AB  - Ambulatory blood pressure monitoring has been steadily growing in popularity as
      equipment becomes more accurate, affordable, and patient-friendly. In addition,
      software packages are more powerful and physician-customizable, and more
      physicians are accepting of ambulatory blood pressure monitoring's advantages.
      Summarizing the studies that deal mainly with hemodialysis patients, there are
      clear advantages to using more than isolated pre- and posthemodialysis blood
      pressure readings. If enough predialysis blood pressure readings are taken and
      averaged, this is a reasonable guide to end-organ damage (ie, left ventricular
      hypertrophy). Home and ambulatory blood pressure-derived values are
      complementary, and only this approach can discern any further contribution from
      diurnal blood pressure elevation. The cross-sectional association between blood
      pressure and end-organ damage is very weak in end-stage renal disease patients if
      the blood pressure values are "casual," but the relationship is much stronger
      when ambulatory blood pressure monitoring-derived measurements are used. One
      prospective study clearly linked the sustained loss of diurnal blood pressure
      fall with sleep with progressive left ventricular dilatation. Loss of circadian
      variation in blood pressure is associated with an increased mortality rate for
      dialysis patients and for diabetic patients, regardless of diabetes type. The
      combination of nondipping in renal impairment leads to a high mortality rate.
      Much more work is needed to dissect out the causes for abnormal diurnal blood
      pressure rhythm and attempt to modulate this parameter. Obstructive sleep apnea
      may be a promising target for intervention.

PMID- 12217256
TI  - Hypertensinogenic mechanism of the calcineurin inhibitors.
AB  - Kidney transplantation has seen a remarkable improvement in allograft survival
      rates and patient survival rates, and an equally remarkable reduction in acute
      rejection rates. Most attribute these changes to the introduction and widespread
      use of calcineurin inhibitors as part of the standard immunosuppressive regimen.
      Cyclosporine and tacrolimus are ideal immunosuppressive agents, much more
      effective and safe than the previous agents used. Especially ironic, however, for
      those caring for kidney transplant patients has been the finding that these
      breakthrough agents are toxic to the kidney and can cause hypertension. We can
      protect the transplanted kidney from rejection, but still damage it paradoxically
      by the protecting agent. Moreover, the prevalence of hypertension in transplant
      clinics has increased (from 40%-50% to up to 90%-100%) as these newer agents have
      gained widespread use. We remain uncertain of the mechanism whereby these agents
      cause hypertension, and therefore remain uncertain of the ideal treatment;
      however, the search for a mechanism has taken us from the organ level to
      intracellular effects of the agents. The fact that both agents cause
      nephrotoxicity suggests that a renal mechanism is at the heart of the
      hypertension.

PMID- 12217257
TI  - Hypertension as a cardiovascular risk factor in end-stage renal failure.
AB  - There is a paucity of high quality studies on the prognostic importance of
      arterial pressure in end-stage renal disease. Furthermore, the optimal timing for
      blood pressure (BP) measurements (pre- or postdialysis), and the prognostic value
      of 24-hour ambulatory BP monitoring in these patients remain to be established.
      In end-stage renal disease patients without diabetes and heart failure,
      predialysis systolic, diastolic, and pulse pressure are strongly and
      independently related to left ventricular mass, and the strength of these
      relationships is higher than that between the corresponding postdialysis values
      and left ventricular mass. Average predialysis systolic pressure (monthly
      average) is associated with left ventricular mass as strongly as 24-hour systolic
      BP, which suggests that the average routine predialysis BP taken over 1 month may
      be equally representative of the "true" BP (the integrated BP load) than 24-hour
      ambulatory BP monitoring. Mortality is U shaped in large hemodialysis databases.
      In the only prospective study that adequately controlled for cardiac function at
      baseline, it was shown that hypertension is associated with a higher risk of
      developing congestive heart failure, and that patients with left ventricular
      hypertrophy or chronic heart failure are at a much higher risk of mortality than
      patients without these complications. The role of arterial stiffening (pulse
      pressure) as a cardiovascular risk factor has been firmly established in an
      analysis of a very large dialysis database in the United States, and by recent
      studies based on direct measurements of pulse wave velocity.

PMID- 12217258
TI  - Microalbuminuria in type 1 and type 2 diabetes mellitus: evidence with
      angiotensin converting enzyme inhibitors and angiotensin II receptor blockers for
      treating early and preventing clinical nephropathy.
AB  - A cumulative incidence of diabetic nephropathy of 25% to 40% has been documented
      after duration of diabetes of at least 25 years in both type 1 and type 2
      diabetic patients. Diabetic nephropathy has become the leading cause (25%-44%) of
      end-stage renal failure in Europe, the United States, and Japan. Until the early
      1980s, no renoprotective treatment was available for use in diabetic nephropathy.
      Death occurred on average 5 to 7 years after the onset of persistent proteinuria.
      The two main treatment strategies for prevention of diabetic nephropathy are
      improved glycemic control and blood pressure lowering, particularly using drugs
      blocking the renin-angiotensin system. Megatrials and meta-analyses have clearly
      demonstrated the beneficial effect of both the above-mentioned treatment
      modalities. Secondary prevention, that is, treatment modalities applied to
      diabetic patients at high risk for developing diabetic nephropathy (eg, those
      with microalbuminuria) has been documented, applying angiotensin converting
      enzyme inhibitors and angiotensin II receptor blockade. The renoprotective
      effects of these drugs are independent of their beneficial reduction in blood
      pressure.

PMID- 12217259
TI  - Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers:
      evidence for and against the combination in the treatment of hypertension and
      proteinuria.
AB  - Several treatment guidelines have made strong recommendations to physicians that
      treatment of nephropathy and hypertension should be based on the use of a long
      acting angiotensin converting enzyme (ACE) inhibitor if tolerated. The recently
      published clinical trials, based on angiotensin II receptor blockers' effects on
      diabetic nephropathy and essential hypertension, have also shown significant
      endpoint reduction. Perhaps the time has come to broaden the recommendations to
      include the use of a renin-angiotensin-aldosterone system altering drug. But what
      if the treatment goal cannot be reached, and incessant proteinuria and high blood
      pressure levels persist despite high dosage treatment of either drug? How should
      this be handled? The dual blockade principle can possibly provide the solution by
      obtaining the broadest and most efficient blockade of circulating angiotensin II
      by using the combination of an ACE inhibitor and an angiotensin II receptor
      blocker. But large clinical trials are yet to come, and at present large endpoint
      trials have not been published. This article provides an overview of how far we
      have come with dual blockade treatment in hypertension and nephropathy.

PMID- 12217261
TI  - Psychosocial predictors of healthful dietary behavior in adolescents.
AB  - OBJECTIVE: To identify predictors of healthful dietary practices in adolescents
      using the Theory of Planned Behavior and determine how gender and ethnicity
      influence the relationship among the theoretical constructs. DESIGN: Initial and
      1-month follow-up questionnaires, designed to measure the constructs of the
      Theory of Planned Behavior and select demographic items, were administered to the
      participants in the spring of 1997 to gather data for this descriptive research.
      SETTINGS/PARTICIPANTS: A sample of 780 adolescents, aged 14 to 19 years, was
      recruited from randomly selected science classes at 4 public high schools in San
      Bernardino, California. Seven hundred and fifty participants (96%) completed the
      initial questionnaire and 672 (86%) completed the follow-up questionnaire.
      ANALYSIS: A 5-step hierarchical multiple regression procedure, general linear
      model analysis, and Tukey's honestly significant difference post hoc test were
      used to analyze the data. RESULTS: Intention to eat a healthful diet was a
      predictor of healthful dietary behavior. Intention was influenced most by
      attitude and then by perceived behavioral control and subjective norm. Those with
      positive attitudes toward healthful eating believed that they would like the
      taste of healthful foods, feel good about themselves, tolerate giving up foods
      that they like to eat, and lose weight or maintain a healthful weight. Mother,
      siblings, and friends were identified as important predictors of subjective norm.
      Knowledge about how to eat a healthful diet, availability of healthful foods,
      motivation, and access to enough money were salient facilitating factors related
      to perceived behavioral control. Interesting contrasts among gender and ethnic
      groups also were noted. CONCLUSIONS AND IMPLICATIONS: The findings indicate that
      multiple attitudinal, normative, and control factors influence healthful dietary
      behavior in adolescents. The synergistic use of these factors in the development
      and implementation of nutrition education interventions may assist in the
      promotion of healthful eating among teens from culturally diverse communities.

PMID- 12217260
TI  - Angiotensin II and progressive renal insufficiency.
AB  - The inhibition of angiotensin II through angiotensin converting enzyme inhibitors
      or angiotensin receptor blockers has become the foundation of medical treatment
      of progressive chronic renal disease. Although these drugs provide a significant
      improvement over earlier treatments, they only slow the progression of renal
      disease, implying the need for additional drugs that could be combined with
      antiangiotensin treatment. Potentially valuable novel drug targets include
      downstream mediators of angiotensin II such as transforming growth factor-b,
      plasminogen activator inhibitor-1, and endothelin-1. In addition, recent evidence
      points to aldosterone as a major player in progressive renal disease, indicating
      that multiple points of the renin-angiotensin-aldosterone system might have to be
      targeted. This paper reviews the experimental and clinical evidence indicating
      that targeting these cytokines and hormones could provide additional benefits to
      antiangiotensin treatment in chronic renal disease.

PMID- 12217262
TI  - Frequency and duration of food insecurity and hunger in US households.
AB  - OBJECTIVE: This study examines the extent to which food insecurity and hunger in
      US households are occasional, recurring, or frequent/chronic. Design/Variables:
      The federal food security scale measures the severity of food insecurity in
      surveyed households and classifies households as to their food security status
      during the previous year. The Current Population Survey Food Security Supplement
      (CPS-FSS) collects the data elements used to calculate the food security scale.
      Supplementary data on the frequency of occurrence of the behaviors and
      experiences comprising the food security scale are also collected by the CPS-FSS,
      but most of this information is not included in the food security scale. This
      study analyzes these supplementary data along with the food security scale and
      its constituent items using data from the Food Security Supplement of the
      nationally representative CPS conducted in August 1998. RESULTS: About two thirds
      of households classified as food insecure by the federal food security scale
      experience the condition as recurring, and around one fifth experience these
      conditions as frequent or chronic. The monthly prevalence of hunger is about 60%
      of the annual prevalence, and the daily prevalence is about 13% to 18% of the
      annual prevalence. CONCLUSIONS AND IMPLICATIONS: Nutritionists can use these
      findings to enhance the informative value of food insecurity and hunger
      statistics from national, state, and local surveys when interpreting them to
      policy makers and to the general public.

PMID- 12217263
TI  - Comparison of baseline fat-related eating behaviors of Puerto Rican, Dominican,
      Colombian, and Guatemalan participants who joined a cholesterol education
      project.
AB  - OBJECTIVE: The objective is to compare baseline fat-related eating behaviors
      among Hispanic subgroups who joined a cholesterol education research project in
      New England. DESIGN: Participants attended baseline screenings as part of the
      study. They had their height, weight, and blood cholesterol measured and
      completed baseline surveys with demographic, risk factor, dietary, and
      psychosocial questions. PARTICIPANTS: A total of 370 Puerto Rican, 210 Colombian,
      357 Dominican, and 102 Guatemalan subjects participated in the baseline. MAIN
      OUTCOME MEASURES: Dietary behavior was measured using the Food Habits
      Questionnaire (FHQ), which was originally developed to assess food choices and
      preparation patterns related to adopting a low-fat diet. Measures include FHQ fat
      summary scores (a reflection of total fat intake), fat behavior subscales, and
      individual fat-related behaviors. ANALYSIS: Analysis of variance was used to
      compare FHQ fat summary scores and multivariate analysis of variance was used to
      compare fat behavior scores and individual food item scores for the 4 Hispanic
      subgroups. Age and gender were covariates in the models. RESULTS: Puerto Rican
      participants had a significantly higher mean FHQ fat summary score than
      Dominicans and Guatemalans and a higher prevalence of many fat-related eating
      behaviors. Although there were some differences by subgroup, the 4 most prevalent
      fat-related behaviors were similar: cooking with fat/oil, eating higher-fat
      sweets, eating higher-fat snacks, and eating dinners with meat. CONCLUSIONS AND
      IMPLICATIONS: Future educational programs and materials for diverse Hispanic
      audiences in the northeastern United States should include the above issues;
      however, educational materials and programs ought to be tailored to individuals
      whenever possible. Efforts may need to focus on Puerto Ricans, who had a higher
      prevalence of many fat-related behaviors in this study.

PMID- 12217264
TI  - Preschool children's acceptance of a novel vegetable following exposure to
      messages in a storybook.
AB  - OBJECTIVE: To investigate whether children's books affect attitudes and behaviors
      pertaining to an unfamiliar vegetable. DESIGN: Nine Head Start classes were
      randomly assigned to a positive, negative, or control group. Data were collected
      through individual interviews on a pretest day and two book-reading (posttest)
      days. PARTICIPANTS: 118 children, ages 3 to 5. INTERVENTIONS: Children's book
      with prominent positive or negative messages about kohlrabi. MAIN OUTCOME
      MEASURES: Children's familiarity with kohlrabi, willingness to taste it, and
      attitudes toward kohlrabi and vegetables in general. ANALYSIS: Chi-square and
      logistic regression. RESULTS: There were significantly more kohlrabi tasters in
      the positive-message group than in the control group during the second posttest
      (P <.05). Primary factors in willingness to taste kohlrabi during the second
      posttest were being exposed to the positive-message treatment (P =.0398) and
      reporting in the previous interview that they would taste kohlrabi again (P
      =.0026). CONCLUSIONS AND IMPLICATIONS: Further study is needed to verify these
      findings and to determine whether the results generalize to other foods and/or
      other children.

PMID- 12217265
TI  - Couples' gender role preferences and management of family food preferences.
AB  - OBJECTIVE: To learn how couples stratified by gender role preference (GRP) manage
      food preferences. DESIGN: One-time individual semistructured qualitative
      interview with each partner in a couple representing 1 of 3 GRP pairings.
      SETTINGS/PARTICIPANTS: Volunteers were recruited using advertising and snowball
      sampling and met the criteria of both parents living at home, wife no older than
      40 years, and at least one child under age 6 years and, if present, all others
      under age 18 years. Both partners in volunteer couples completed a 31-item GRP
      scale, and the scores of each partner were categorized as traditional (lowest 25%
      of possible scores), transitional (middle 50%), or egalitarian (top 25%). No
      traditional couples volunteered. A purposeful sample of 10 transitional and 10
      egalitarian wives representing 20 couples was interviewed. VARIABLES MEASURED:
      Each partner was asked how food preference patterns were established and how
      family member food preferences affect foods served at evening meals now.
      ANALYSIS: Thematic content analysis, constant comparison, and consensus produced
      the final thematic analysis. RESULTS: Transitional wives married to transitional
      husbands established a pattern of deference to the husband's preferences that
      could make alteration of food choices difficult. Egalitarian wives married to
      egalitarian husbands established a fairer pattern of balancing partner's food
      preferences. CONCLUSIONS AND IMPLICATIONS: Nutrition education for transitional
      and egalitarian couples should use different approaches.

PMID- 12217266
TI  - Content analysis: review of methods and their applications in nutrition
      education.
AB  - Content analysis is a set of qualitative and quantitative methods for collecting
      and analyzing data from verbal, print, or electronic communication with numerous
      applications in nutrition education research. Textual information from
      interviews, focus groups, and open-ended survey questions can be evaluated using
      content analysis. Selection of method(s) depends on the type(s) and length of
      material to be analyzed, results desired, and researchers' preferences and
      technological capabilities. This article reviews options available to content
      analysts--from manual to fully computerized. Overcoming the challenges inherent
      in using these methodologies is recommended because of their usefulness in the
      information-based messaging discipline of nutrition education.

PMID- 12217267
TI  - Study abroad: foodways and nutrition in the traditional Mediterranean diet.

PMID- 12217268
TI  - [Alzheimer's caregiver burden and psychological distress. A neglected association
      in the assessment of dementias].
AB  - INTRODUCTION: Caregivers of dementia patients have a high risk of developing
      mental disorders. Nevertheless, their burden is not routinely assessed during the
      clinical assessment of the Alzheimer's type dementia patients. This study was
      designed to evaluate the association between caregiver's burden and psychological
      distress and to estimate the prevalence of mental disorders among the caregivers.
      METHODS: Cross-sectional study of Alzheimer patients' caregivers (n = 40). The
      caregiver burden was assessed by the Zarit scale whereas the GHQ-28 was used to
      evaluate psychological distress. RESULTS: The Zarit caregiver burden scale was
      able to discriminate the psychic distress levels (area under the curve: 0.87; 95%
      CI: 0.77 0.98). Its sensitivity (93%; 95% CI: 68.0 99.8) and specificity (80%;
      95% CI: 59.3 93.2) were good for a cut-off point of 62/63. The estimated
      prevalence of psychiatric disorders in the caregivers was 20.7% (95% CI: 0.0
      60.0%). CONCLUSION: The Zarit caregiver burden scale is useful for assessing
      psychological distress and should be included in any clinical protocol devised to
      evaluate the needs of patients with dementia.

PMID- 12217269
TI  - [Eating attitudes and body satisfaction in adolescents: a prevalence study].
AB  - OBJECTIVES: To determine the prevalence of possible TCA in a sample of
      adolescents of either sex, in habitants of Girona, as well as to determine the
      relations between eating attitudes and body shape concerns in adolescent girls.
      SU BJECTS AND METHOD: The study sample was composed of all adolescent man and
      women (n=1025), students from Girona, with ages comprised between 14 and 19. The
      questionnaires used where the EAT-40 (being values over 30 the cut-off point) and
      the BSQ. RESULTS: While a 16.3% of adolescent women present potential risk of
      TCA, only 0.4% adolescent men have the same risk. A 9% of adolescent women show
      an extreme concern for her body shape and weight, and 13.1% show a moderate
      worry. Adolescent women that showed the highest symptomatology associated with
      eating disorders also present a higher dissatisfaction and concern with body
      shape (r=.65). CONCLUSIONS: The prevalence of possible TCA in Girona city is
      similar to the one found in other studies. This high prevalence makes necessary
      the implementation of prevention strategies in younger people.

PMID- 12217270
TI  - [Symptoms of psychopathology. Identification and interpretation].
AB  - INTRODUCTION: Updating psychopathology is currently viewed as being dependent on
      a readjustment that fits the ever increasing knowledge of cerebral
      physiopathology. Nevertheless, this recalibration cannot elude the apories of a
      medical semiology based upon the identification of correlates and injury as the
      reference of symptoms. Experience is proposed as the true field of
      psychopathological research, the totality concept being one of them. MATERIAL AND
      METHODS: The publications of those authors who have dealt with the concept of
      totality are reviewed in addition to the basis of each approach and its ties with
      each author's contribution to psychopathology. RESULTS AND DISCUSSION: We observe
      that the totality concept has been subjected to determinant procedures that are
      not capable of abiding to the demand of totality as a structure of experience.
      CONCLUSIONS: Meaningful relationships between totality and symptoms are
      considered as a possible alternative to positivism-oriented processes of
      identification.

PMID- 12217271
TI  - [Panic disorder and transcranial magnetic stimulation].
AB  - Transcranial magnetic stimulation (TMS) has been tried in some Anxiety Disorders
      (Obsessive-compulsive disorder and Posttraumatic Stress Disorder) with different
      results. We present a pilot study including three Panic Disorder patients. The
      subjects who were enrolled had a history of the disease for at least 1 year and
      they had unsuccessfully followed psychotherapy and pharmacological treatment. The
      patients received 10 sessions during two weeks; each session lasted 30 trains of
      60 seconds at a frequency of 1 Hz, on the right dorsolateral prefrontal cortex,
      at 110% of the motor threshold. All three patients experienced a modest and
      partial symptom improvement that did not seemed to be clinically relevant. Two
      patients accepted to participate in a TMS second phase, where the previous
      stimulation parameters were alternated with an application of 30 trains of 20 Hz
      during 2 seconds on the left prefrontal cortex. This alternate application of
      high and low frequency TMS in each session was also well tolerated, but failed to
      produce additional improvement. In addition to presenting these three cases, we
      emphasize some features concerning the neurobiological basis of the anxiety
      disorders and we connect them to the previously described TMS neurophysiological
      actions in order to justify further investigation.

PMID- 12217272
TI  - [Assessment of the Life Skills Profile and the Brief Psychiatric Rating Scale as
      predictors of the length of psychiatric hospitalization].
AB  - INTRODUCTION: Length of hospital stay is generally used as an indirect indicator
      of effectiveness and efficiency of treatment programs, but it is uncommon that
      other factors related with hospital stay are also contemplated. The aims of this
      study are to analyse the relationship between illness severity and adaptative
      behavior and to assess the predictive power of both constructs on the length of
      hospital stay. METHODS: Multicenter prospective study (n = 132). The outcome
      variable is the length of hospital stay cut off at 90 days. The illness severity
      (BPRS) and the adaptative behavior (LSP) of psychiatric patients are explanatory
      variables. RESULTS: After adjusting for age, gender and psychiatric diagnosis,
      negative symptoms (OR = 2.3; 95%CI = 1.3 4.1), self-competence (OR = 0.85; 95% CI
      = 0.78 0.93), and the total LSP score (OR = 0.96; 95% CI = 0.93 0.98), were
      significantly associated to the length of hospital stay. These three variables
      shared a similar predictive power (chi2 = 1.9 on 2 d.f.; P = 0.4). CONCLUSION:
      Deficits in adaptative behaviour are as relevant as negative symptoms to explain
      the length of hospital stay. Both assessment domains should be included in the
      administrative information at discharge.

PMID- 12217273
TI  - [Psychiatric disorders, personality and traumatic experiences in conversive non
      epileptic seizures patients].
AB  - AIM: To study the clinical characteristics in patients with conversion non
      epileptic seizures, and the influence that traumatic childhood experiences could
      have in their psychopathologic status and personality. METHODS: Seventeen
      patients with non-epileptic seizures confirmed through video-EEG were included. A
      structured clinical interview (SCID-DSM-III-R), a measure of personality
      variables (MMPI), and an interview designed for collecting data on personal
      history of childhood traumas were administered. Descriptive and comparative
      statistical methods were used. RESULTS: More than 70% of the sample fulfilled the
      criteria for two or more simultaneous diagnoses in Axis I, and for at least one
      personality disorder. The subgroup experiencing childhood traumatic experiences
      showed more clinically significant MMPI scales, a younger age at correct
      diagnosis, and higher scores on the MMPI psychastenia and psychopathic deviation
      scales than the non experiencing childhood traumatics events. CONCLUSIONS: Our
      sample of patients with conversion non-epileptic seizures shows a significant
      level of psychopathology, and the absence of a unique character substrate. Under
      the generic term of pseudoseizures, a number of subgroups according to childhood
      traumatic experiences, with different levels of severity and different clinical
      and personality properties, may be defined.

PMID- 12217274
TI  - [Serotonergic activity and harm avoidance in abstinent drug addicts].
AB  - INTRODUCTION: The present study was to assess the relationship between the
      Tridimensional Personality Questionnaire scores and the 5-HT activity in
      abstinent drug addicts. METHODOLOGY: 16 men who satisfied the DSM-III-R/DSM-IV
      criteria for substance abuse disorder accomplished the Cloninger's Tridimensional
      Personality Questionnaire; their serotonergic activity was measured using the
      Fenfluramine Challenge Test. RESULTS: The Novelty Seeking is the only dimension
      showing a statistical difference versus a standard healthy sample, while harm
      avoidance and not the other dimensions was significantly correlated with the
      prolactin post-fenfluramine peak (r= 0.80, p<0.001). CONCLUSION: This work
      confirm that drug addicts are high Novelty Seekers and support the hypothesis
      that Harm Avoidance dimension correlate with serotonergic activity.

PMID- 12217275
TI  - [Factors associated with antidepressive placebo response: a review].
AB  - The placebo effect is a well-known phenomenon through medicine and has been used
      as a treatment in many different pathologies. Nowadays it is being used as a
      control for the design of trials about the new psychotropic drugs. Within
      Psychiatry and more specifically regarding the affective disorders, responses to
      the use of inactive substances have been more frequently described and the rates
      recorded go from 20% to 49%.We have made a review of the literature published in
      this field in order to identify the predictors which are possibly involved in
      those patients with depression who have positive or negative responses to
      placebo. The most significant data come from the social, nosological, clinical,
      evolutive and, above all, neuroendocrinologic predictors. To finish, it is
      important to remark how inconsistent and heterogeneous is the response to
      placebo, as well as the ethic and legal problems that its use can carry.

PMID- 12217276
TI  - [Mental health services evaluation].
AB  - The evaluation of the community mental health services to the chronic mental
      health patients is one of the areas of more interest since the psychiatric reform
      began. To carry out an evaluation of the attention in depth it is necessary to
      keep in mind many different aspects. The new conception of the mental health
      services has implied a change in the whole system. The evaluation process can be
      divide in three levels: structures, processes and results which are interrelated
      to each other. For each one of these levels specific indicators exist and all
      should complete a minimum requirements as being valid, objectives, sensitive and
      specific. For a good evaluation and planning of mental health services is
      necessary to know what type of services are implied in the attention, which are
      the patients that go to the services and which are the changes that have taken
      place in this patients.

PMID- 12217277
TI  - [Abuse, tolerance and dependence of zolpidem: three case reports].
AB  - Zolpidem is an imidazopyridine, which acts at the benzodiacepine omega1 receptor
      subtype. Zolpidem was marketed as a short-acting hypnotic and it was assumed that
      had a lower potential for abuse than benzodiacepines. Since 1993, several cases
      of zolpidem dependence have been reported. We have observed three patients with
      abuse, dependence and withdrawal syndrome to zolpidem. Two of them had history of
      drugs abuse and all of them developed withdrawal symptoms when discontinuing it.
      In Spain, zolpidem may be sold without medical prescription like other non
      benzodiacepines hypnotics and it may be playing an important role in the increase
      of abuse cases. We think zolpidem should be considered as a benzodiacepine with
      the same control and regulation.

PMID- 12217278
TI  - Vascular injury complicating lumbar disc surgery. A systematic review.
AB  - OBJECTIVES: to review the literature concerning the early and late vascular
      complications of lumbar disc surgery. METHODS: using the MEDLINE database, we
      reviewed all reports of vascular complications associated with surgical excision
      of a prolapsed disc via a posterior approach reported in the English literature
      since 1965. RESULTS: we identified 98 cases of vascular complications for an
      incidence of 1-5 in 10000 disc operations. Early presentation is shock due to
      rupture of a large retroperitoneal vessel. Late complications include development
      of pseudoaneurysms and arteriovenous fistulas. Treatment of a vascular tear
      consisted mainly of primary suturing of the injured vessel. The preferred method
      for arteriovenous fistula and pseudoaneurysm repair was suturing from within the
      arterial lumen along with interposition grafting. Recently, endovascular
      techniques have been recommended, lowering the high morbidity and mortality
      related to conventional repair. CONCLUSION: iatrogenic vascular injury during
      lumbar disc surgery, although rare, should be suspected if signs of circulatory
      instability are noted or if lumbar pain, leg oedema or high output cardiac
      failure develop months to years following such surgical procedures. However,
      these symptoms may arise during or immediately after surgery, requiring immediate
      intervention.

PMID- 12217279
TI  - Does fibrin glue reduce complications after femoral artery surgery? A randomised
      trial.
AB  - OBJECTIVES: to determine whether application of fibrin glue before closure of
      inguinal wounds reduces the incidence of lymphatic complications. DESIGN: we a
      prospective randomised trial. MATERIALS AND METHODS: 224 consecutive patients
      were enrolled. The wounds were randomly assigned to standard closure (group A, n
      = 134) or closure with application of fibrin glue (group B, n = 132). The
      incidence of local lymphatic and non-lymphatic complications, the amount of
      lymphatic fluid collected, and the time to drain removal were compared in the
      groups. RESULTS: the incidence of lymphatic complications was 19% in group A and
      10% in group B (p = 0.027). The average drain output and the time to drain
      removal did not differ in the two groups. The total incidence of non-lymphatic
      local complications was 10% and did not differ in the two groups. CONCLUSIONS:
      fibrin glue application is associated with a significant reduction in lymphatic
      complications.

PMID- 12217280
TI  - Immunotherapy with Mycobacterium vaccae and peripheral blood flow in long-treated
      leprosy patients, a randomised, placebo-controlled trial.
AB  - OBJECTIVE: to evaluate immunotherapy as a means of improving peripheral blood
      flow in chronic leprosy patients. DESIGN: this was a double-blind, randomised,
      placebo-controlled, clinical trial. MATERIALS: heat-killed Mycobacterium vaccae
      1mg plus 0.02 microg Tuberculin protein per 0.1 ml dose in borate buffer, with
      saline as placebo. Those studied were 92 long-treated residents of a leprosy
      centre in Iran, 10 of their healthy children and 10 staff members. Evaluation
      employed the Perimed PF2, Laser-Doppler Flowmeter, a platinum skin thermistor,
      and a thermal sensibility tester. METHODS: single intradermal injections of test
      or placebo were given to 103 patients 18 months before the blinded evaluation.
      Fingerpulp blood flux was measured in controlled conditions and vasomotor
      reflexes and skin sensation to touch, pain and heat were evaluated in 45 and 47
      patients in the placebo and M. vaccae groups, respectively, and in 20 healthy
      control persons. RESULTS: Laser-Doppler flux, skin temperature, vasomotor
      reflexes and sensation were impaired in leprosy patients. Immunotherapy improved
      (p < 0.05) Laser-Doppler flux, skin temperature and temperature sensation.
      CONCLUSIONS: immunotherapy, given 18 months earlier, significantly improved blood
      flow and temperature sensation, in fully-treated, chronic, leprosy patients. The
      same principles might be employed in other conditions of reduced peripheral blood
      flow.

PMID- 12217281
TI  - Early results of thrombolysis vs anticoagulation in iliofemoral venous
      thrombosis. A randomised clinical trial.
AB  - OBJECTIVE: catheter directed thrombolysis has been advocated for complete and
      rapid dissolution of iliofemoral deep venous thrombosis (DVT). The aim of our
      study is to compare, in a randomised trial, local thrombolysis and
      anticoagulation with anticoagulation alone in patients with iliofemoral DVT.
      METHODS: a consecutive series of 35 eligible patients, were randomised to either
      catheter directed thrombolysis followed by anticoagulation or to anticoagulation
      alone. Clot lysis and deep venous reflux were assessed with ultrasound duplex and
      plethysmography after 6 months. RESULTS: complete data were available in the 18
      and 17 patients randomised to thrombolysis and anticoagulation, respectively. At
      6 months, patency rate was better in cases treated with thrombolysis [13/18 (72%)
      vs 2/17 (12%), p < 0.001]. Venous reflux was higher in-patients treated with
      anticoagulant [7 patients (41%) vs 2 (11%), p = 0.04]. CONCLUSION: in the short
      term patients treated with catheter directed thrombolysis obtained better patency
      and competence than those treated with standard anticoagulation.

PMID- 12217282
TI  - Physiological advantages of cerebral blood flow during carotid endarterectomy
      under local anaesthesia. A randomised clinical trial.
AB  - OBJECTIVE: to examine the effects of type of anaesthesia on cerebral blood flow
      during carotid endarterectomy (CEA). DESIGN: prospective randomised study.
      METHODS: thirty-four CEA procedures under local anaesthesia (LA) are compared to
      33 procedures under general anaesthesia (GA). Mean middle cerebral artery
      velocity (MCAV(mean)) was monitored using Transcranial Doppler (TCD) and mean
      arterial pressure (MAP) assessed by continuous intra-arterial blood pressure
      transducer. RESULTS: pre-op MCAV(mean) and MAP were similar in both groups. Pre
      clamp MCAV(mean) was similar in both groups and did not differ from pre-op
      values. With carotid clamping the MCAV(mean) significantly dropped in both
      groups. The post-clamp MCAV(mean) was significantly less in the GA group (p <
      0.05), and the percentage reduction in MCAV(mean) significantly more for GA
      procedures (p < 0.05). Pre-clamp MAP was significantly elevated in LA procedures
      and significantly lowered in GA procedures. Pre-clamp MAP was significant less
      for GA procedures (p < 0.001). Post clamp MAP did not differ from pre-clamp
      levels in either group. There was no correlation between MCAV(mean) and MAP.
      Complication rate, combined death/stroke rates were similar in each group.
      CONCLUSION: LA CEA is associated with better preservation of the ipsilateral
      cerebral circulation and increased tolerance of the effects of carotid clamping.
      Changes in MCAV(mean) cannot be explained by variations in blood pressure between
      the two techniques.

PMID- 12217283
TI  - Which stress test is superior for perioperative cardiac risk stratification in
      patients undergoing major vascular surgery?
AB  - OBJECTIVE: to compare the additional prognostic value of Dobutamine Stress
      Echocardiography (DSE), Dipyridamole Stress Echocardiography (DiSE) and Perfusion
      Scintigraphy (DTS) on clinical risk factors in patients undergoing major vascular
      surgery. DESIGN: retrospective analysis. MATERIALS: 2204 consecutive patients who
      underwent DSE (n=1093), DiSE (n=394), or DTS (n=717) testing before major
      vascular surgery were studied. METHODS: primary endpoint was a composite of
      cardiac death and non-fatal myocardial infarction (MI). Logistic regression
      analysis was performed to evaluate the relation between cardiac risk factors,
      stress test results and the incidence of the composite endpoint. RESULTS: there
      were 138 patients (6.3%) with cardiac death or MI. Patients with 0, 1-2, and 3 or
      more risk factors experienced respectively 3.0, 5.7 and 17.4% cardiac events. We
      found no statistically significant difference in the predictive value of a
      positive test result for DiSE and DSE (Odds ratio (OR) of 37.1 [95% CI, 8.1
      170.1] vs 9.6 [95% CI, 4.9-18.4]; p=0.12), whereas a positive test result for DTS
      had significantly lower prognostic value (OR=1.95 [95% CI, 1.2-3.2]). CONCLUSION:
      a result of stress echocardiography effectively stratified patients into low- and
      high-risk groups for cardiac complications, irrespective of clinical risk
      profile. In contrast, the prognostic value of DTS results was more likely to be
      dependent on patients' clinical risk profile.

PMID- 12217284
TI  - Quinupristin/dalfopristin bonding in combination with intraperitoneal antibiotics
      prevent infection of knitted polyester graft material in a subcutaneous rat pouch
      model infected with resistant Staphylococcus epidermidis.
AB  - OBJECTIVE: to investigate the efficacy of quinupristin/dalfopristin in the
      prevention of prosthetic graft infection in a rat subcutaneous pouch model.
      METHODS: graft infections were established in the subcutaneous tissue of 140 male
      Wistar rats by implantation of Dacron prostheses followed by topical inoculation
      with Staphylococcus epidermidis with intermediate resistance to glycopeptides.
      The study included one group without contamination, one contaminated group
      without prophylaxis, one contaminated group that received 50mg/l
      quinupristin/dalfopristin-soaked graft, one contaminated group that received
      10mg/kg intraperitoneal levofloxacin, one contaminated group that received 3mg/kg
      intraperitoneal doxycycline, and two contaminated groups that received 50mg/l
      quinupristin/dalfopristin-soaked plus 10mg/kg intraperitoneal levofloxacin or
      3mg/kg intraperitoneal doxycycline. Each group included 20 animals. The grafts
      were removed after 7 days and evaluated by quantitative culture. RESULTS:
      quinupristin/dalfopristin showed a significantly higher efficacy than
      levofloxacin and doxycycline, even though quantitative graft cultures for rats
      that received only quinupristin/dalfopristin-soaked graft showed bacterial
      growth. Otherwise, the efficacy of levofloxacin was similar to that of
      doxycycline. Only the group treated with quinupristin/dalfopristin combined with
      levofloxacin or doxycycline showed no evidence of staphylococcal infection.
      CONCLUSIONS: quinupristin/dalfopristin as adjunctive topical antibiotic
      prophylaxis can be useful for the prevention of vascular graft infections caused
      by staphylococcal strains with high levels of resistance.

PMID- 12217285
TI  - Characteristics of deep vein thrombosis associated with prolonged travel.
AB  - OBJECTIVES: to identify the incidence of prolonged travel among consecutive
      patients with deep venous thrombosis (DVT) and to investigate any differences in
      the patterns of traveller's thrombosis versus DVT's with no history of prolonged
      recent travel. METHODS: of 137 consecutive patients, who were confirmed to have
      DVT by duplex ultrasonography, 36 were excluded because of either prolonged
      immobilisation or recent surgery. All patients were asked whether they had
      travelled within 2 weeks for more than 3h. The presence of other classic risk
      factors for DVT was also recorded. Patients who were unlikely to travel as a
      result of prolonged immobility for more than 2 weeks and those who underwent
      surgery within 2 weeks were excluded from the study. The extent and location of
      thrombi was also verified by duplex scanning in each patient. RESULTS: of 101
      patients, eligible for the final analysis, 15 (15%) claimed to have a recent
      travel, of whom 9 (9%) travelled by air. By comparison of a group of 106 patients
      with similar symptoms at presentation, but who had negative duplex finding 12
      (11%) had a history of prolonged travel (p=0.8, Fisher's exact test). Travel
      related DVT occurred to a significantly younger age group than non travellers.
      Thirteen (87%) out of 15 patients with travel-related DVT had another coexisting
      risk factor and 7 out of 10 patients had a positive thrombophilia screen.
      CONCLUSION: The majority of those with travel-related DVT had other concomitant
      risk factors and a high incidence of a positive thrombophilia screen, suggesting
      that travel itself may act as an additive risk among those with pre-existing risk
      factors for DVT.

PMID- 12217286
TI  - The impact of the carotid plaque type on restenosis and future cardiovascular
      events: a 12-year prospective study.
AB  - OBJECTIVES: to evaluate the impact of the carotid plaque type on recurrent
      carotid stenosis, future cardiovascular events and patients' survival. DESIGN:
      open prospective study. PATIENTS AND METHODS: three hundred and eight patients
      who underwent a total of 338 carotid endarterectomies were included in the study.
      All of the patients were evaluated postoperatively with clinical examination and
      colour duplex 1 month after the operation and every 6 months thereafter. Mean
      duration of follow-up was 63 months (range: 12-144). Eight patients (3%) were
      lost to follow-up. Restenoses, cardiovascular events and deaths were recorded and
      analysed with regard to the traditional risk factors and the ultrasonographic
      characteristics of the plaques. Statistical analysis was performed using the
      Kaplan-Meier method, the log rank test and Cox regression analysis. RESULTS:
      cumulative restenosis rate at 10 years of follow-up was 21% and was associated
      with coronary artery disease (p=0.01) and echolucent plaques (p=0.02). Life-table
      analysis showed a 10-year survival rate of 64% and a 10-year rate of
      cardiovascular events of 41%. Hypertension (p=0.003), coronary artery disease
      (p=0.002) and echolucent plaques (p=0.01) were associated with a higher incidence
      of cardiovascular events.

PMID- 12217287
TI  - Infrainguinal arterial reconstruction: female gender as risk factor for outcome.
AB  - OBJECTIVES: the effect of gender on the long-term results of infrainguinal
      arterial reconstruction are poorly investigated. METHODS: all patients undergoing
      infrainguinal arterial reconstruction with an autogenous vein are as 11 years
      period was prospectively evaluated. RESULTS: four hundred and fifty
      reconstructions (292 man, 160 women) were performed as on 416 patients. Thirty
      day mortality was 1.1% (n=5). Women were on average older (74 vs 68; p<0.001) and
      disease was more advanced (81 vs 68%,p =0.013 with stage of critical ischaemia).
      Primary (58 vs 61%) and primary assisted patency rates (82 vs 84%) were
      comparable. Limb salvage and survival after 60 months were not different. On
      multivariate analysis age and stage of the disease were independent variables for
      patency and survival. Diabetes and gender reached statistical significance as
      predictors of limb salvage only. CONCLUSION: age and stage of the disease were
      independent predictors for patency and survival, diabetes and gender for limb
      salvage.

PMID- 12217288
TI  - Outcome of venous stasis ulceration when complicated by arterial occlusive
      disease.
AB  - OBJECTIVE: to report the outcome of patients with venous stasis ulceration (VSU)
      and severe arterial occlusive disease (AOD). DESIGN: retrospective study.
      METHODS: using the International Classification of Diseases (ICD-9), codes for
      VSU and AOD were cross-matched to identify patients from 1989 to 1999 at two
      tertiary hospitals. Entry into the study required the presence of a VSU and an
      ipsilateral procedure to improve AOD or major amputation during the same
      hospitalisation. RESULTS: fourteen patients (15 extremities) with a mean age of
      80 years (range: 47-93) were identified as having VSU and AOD. Mean duration of
      VSU up to the time of revascularisation or amputation was 6.4 years (range: 4
      months-21 years). The mean number of VSUs per extremity was 2.1 and mean wound
      area was 71 cm(2). Mean ankle-brachial index was 0.46 (range: 0.10-0.78). Nine
      extremities (60%) had a bypass procedure, 3 (20%) had an interventional
      procedure, 1 (0.6%) had a lumbar sympathectomy, and 2 (13%) had an amputation.
      Over a mean follow-up of 2.8 years, 3 extremities (23%) healed of which 2
      recurred. On last review, 11 patients with 12 afflicted extremities had expired.
      Nine of the remaining 10 extremities were not healed at the time of death. Eight
      of nine bypass grafts remained patent in follow-up or at death and subsequent
      limb salvage was 100%. CONCLUSIONS: combined VSU and AOD represents a rare
      condition predominantly found in elderly patients with multiple comorbidities.
      Few patients had complete healing despite an arterial inflow procedure and
      mortality was high over the short term.

PMID- 12217289
TI  - Areas of concern, quality of life and life satisfaction in patients with
      peripheral vascular disease.
AB  - OBJECTIVES: to explore the ways in which peripheral vascular disease subjectively
      affect patients and to relate these findings to validated measurements of quality
      of life (QOL) and life satisfaction. DESIGN: a cross-sectional study. SUBJECTS:
      eighty patients, with carotid artery stenosis (CAS), abdominal aortic aneurysm
      (AAA), intermittent claudication (IC) or critical limb ischaemia (CLI). METHODS:
      semi-structured interviews were used to explore the effect of the disease on the
      patients life situation. QOL was assessed by SF-36 and life satisfaction by LiSat
      11. RESULTS: the SF36, LiSat-11 and our interview revealed two principal
      patterns: one for patients with CAS and AAA, and one for patients with IC and
      CLI. The interview revealed important areas affecting the vascular patient. Some
      of these areas: higher intellectual function, concern, sexual function, family
      concern and factors related to the operated areas were not covered by either the
      SF36 or the LiSat-11. CONCLUSIONS: for a full understanding of how peripheral
      vascular disease affects the individual, disease specific questions need to be
      added to generic QOL instruments and measurements of life satisfaction.

PMID- 12217290
TI  - The -174 G/C polymorphism of the interleukin-6 gene promoter is associated with
      peripheral artery occlusive disease.
AB  - OBJECTIVE AND DESIGN: high plasma levels of Interleukin-6 (IL-6) are found in
      patients with atherosclerotic disorders. Recently, a common polymorphism of the
      IL-6 gene promoter, influencing the transcription rate of the gene, has been
      described and associated with atherosclerosis of carotid and coronary arteries.
      The objective of this study was to test whether IL-6 gene promoter polymorphism
      is associated with peripheral artery occlusive disease (PAOD) in a case-control
      study. METHODS: IL-6 gene promoter polymorphism was evaluated by polymerase chain
      reaction followed by restriction enzyme analysis in 84 patients affected by PAOD
      and 183 controls. RESULTS: the distribution of IL-6 genotypes was: patients with
      PAOD: 44 GG, 30 GC, 10 CC; control subjects: 53 GG, 80 GC, 50 CC. The GG genotype
      was significantly more common in the PAOD group (p<0.0001), while the CC genotype
      was significantly more common in control patients (p=0.005). CONCLUSIONS: this
      study indicates a strong association between IL-6 gene polymorphism and PAOD and
      support the hypothesis that IL-6 and IL-6 gene polymorphism are important in the
      pathophysiology and evolution of ischaemic diseases of the lower limbs.

PMID- 12217292
TI  - Totally laparoscopic aortobifemoral bypass: a new and simplified approach.

PMID- 12217291
TI  - HSP70 expression in skeletal muscle of patients with peripheral arterial
      occlusive disease.
AB  - OBJECTIVES: heat shock protein (HSP70) has been studied in the ischaemic
      myocardium and proven to provide protection against ischaemia. However, HSP70 in
      ischaemic skeletal muscle in patients with peripheral arterial occlusive disease
      (PAOD) has not been reported. METHODS: thirty-four patients with PAOD (Fontaine's
      criteria: stage II: 15; III: 9 and IV: 10, respectively) and ten non-PAOD
      controls were enrolled in the study. Calf muscle samples were taken. HSP70 was
      quantitated by SDS-PAGE using ultrasensitive silver staining with reference to a
      series of standard HSP70, and HSP70 mRNA was estimated using RT-PCR. RESULTS: in
      comparison with the controls [median with range: 24.8 (14.1-35.6) ng in 2.5
      microg total protein], HSP70 was increased significantly in PAOD [stage II: 93.1
      (62.7-114.3); stage III: 110.1 (89.7-134.5) and stage IV: 77.4 (67.3-101.1)].
      Similar results were obtained with HSP70 mRNA. CONCLUSIONS: HSP70 is increased in
      the ischaemic skeletal muscle in patients with PAOD, and HSP70 expression is
      different with regard to clinical stages, and the upregulation of HSP70 mRNA
      implies that the expression of HSP70 seems to be regulated at transcriptional
      level.

PMID- 12217293
TI  - Endovascular repair of spontaneous non-aneurysmal aortocaval fistula.

PMID- 12217294
TI  - Acute thrombosis associated with hyperhomocysteinemia.

PMID- 12217295
TI  - Popliteal aneurysms.

PMID- 12217297
TI  - Surgery: central to the treatment of cancer.

PMID- 12217298
TI  - Molecular prognostic indicators in breast cancer.
AB  - Here we review a panel of oncogene products, proteases and markers of
      proliferation that have shown potential as prognostic indicators in primary
      breast cancer. The relative merits of specific genetic mutations as well as
      alterations at the protein level are discussed. Finally an assessment is made of
      the transfer of knowledge from the laboratory to the bed-side.

PMID- 12217299
TI  - Axillary lymph node ratio and total number of removed lymph nodes: predictors of
      survival in stage I and II breast cancer.
AB  - AIMS: Presence of axillary lymph node metastases is considered the most important
      prognostic factor for breast cancer survival. In a period of increasing
      popularity for the sentinel node procedure, clarity about the possible relation
      between axillary dissection and survival is essential. This study investigated
      whether the total number of removed lymph nodes and the ratio of invaded/removed
      lymph nodes (lymph node ratio (LNR) would prove to be independent prognostic
      factors for survival. METHODS: Data from 453 consecutive patients with stage I or
      II breast cancer were studied retrospectively. The total number of removed lymph
      nodes and the LNR were analysed for their prognostic value in comparison with
      known prognostic factors. RESULTS: Node-negative patients with < 14 lymph nodes
      removed had a 10 year survival of 79% compared with 89% in patients with > or =
      14 lymph nodes removed (P=0.005). The 10 year survival for patients with an LNR >
      or = 0.2 was 52%, compared with 73% for patients with an LNR < 0.2 (P<0.0001). A
      Cox proportional hazards model showed that, for node-negative patients, only age
      and total number of removed lymph nodes were significant prognostic factors. For
      node-positive patients, age, total number of removed lymph nodes and the LNR were
      significant risk factors for survival outcome. The LNR was also significantly
      associated with the presence of distant metastases during follow-up (hazard ratio
      3.56, range 1.63-7.77). CONCLUSIONS: In stage I and II breast cancer, a
      favourable prognosis was found for node-negative patients with > or = 14 removed
      lymph nodes. Before axillary lymph node dissection with its well-defined survival
      prognosis is replaced by less invasive staging methods, long-term survival using
      new staging techniques needs to be defined. For node-positive patients, the LNR
      proved to be an excellent predictor for survival outcome or development of
      metastatic disease. Selection of lymph node-positive patients based on the LNR
      may guide specific adjuvant treatment choices.

PMID- 12217300
TI  - A prospective validated model for predicting axillary node metastases based on
      2,000 sentinel node procedures: the role of tumour location [corrected].
AB  - AIMS: The purpose was to identify the independent predictive factors of axillary
      lymph-node metastases (ALNM) in infiltrating ductal carcinoma (IFDC) and to
      create a prospective, validated statistical model to predict the likelihood of
      ALNM in patients in the present era of sentinel lymph-node (SLN) biopsy and
      enhanced histopathology. METHODS: Univariate and multivariate analyses of 13
      clinicopathological variables (including tumour location) were performed to
      determine predictors of ALNM in 1659 eligible SLN biopsy procedures. A logistic
      regression model was developed and then prospectively validated on a second
      population of 187 subsequent consecutive procedures. RESULTS: Age, pathological
      tumour size, palpability, lymphovascular invasion (LVI), histological grade,
      nuclear grade, ductal histological subtype, tumour location (quadrant) and
      multifocality were associated with ALNM in univariate analyses (P < 0.001). Of
      these, only palpability and histological grade were not statistically associated
      with ALNM in the multivariate analysis (P> 0.05). The frequency of ALNM in upper
      inner-quadrant (UIQ) tumours was 20.6%, compared with 33.2% for all other
      quadrants (P<0.0005). There was no statistical difference between UIQ and other
      quadrant tumours in any clinicopathological variables analysed. The logistic
      regression model, developed based on the population of 1659, had the same
      accuracy, sensitivity, specificity, positive predictive value and negative
      predictive value when applied prospectively to the second population. CONCLUSION:
      Tumour size, LVI, age, nuclear grade, histological subtype, multifocality and
      location in the breast were independent predictive factors for ALNM in IFDC. ALNM
      is less frequent in UIQ tumours than in other-quadrant tumours. Our prospectively
      validated predictive model could be valuable in pre-operative patient
      discussions, although staging of the axilla in the individual patient remains
      necessary.

PMID- 12217301
TI  - Are surgeons effective counsellors for women with a family history of breast
      cancer?
AB  - AIM: In the TRACE (Trial of Genetic Assessment in Breast Cancer) study, the data
      on the time spent by the surgeon with the women with a family history of breast
      cancer was analysed with respect to the changes in the anxiety scores and breast
      cancer worry scores. We wanted to see whether longer consultation times with
      surgeons improved these scores. METHODS: In the TRACE study, women with a family
      history of breast cancer attended a standard breast clinic to be seen by a
      surgeon and nurse specialist. Anxiety scores and breast cancer worry scores of
      these women were recorded prior to attending the clinic and immediately after
      their appointment. RESULTS: In the 274 evaluable women, there was a significant
      improvement in the anxiety and breast cancer worries after surgical consultation
      but it did not correlate with the length of surgical consultation. However, women
      in the high-risk group showed a significant reduction of breast cancer worry
      score with longer consultation (P=0.032). CONCLUSIONS: Spending more time with
      the women with a family history of breast cancer does not help to reduce anxiety
      scores and breast cancer worry scores except in the subset of women who were told
      that their risk of breast cancer was high.

PMID- 12217302
TI  - Adjuvant endocrine treatment (goserelin vs tamoxifen) in pre-menopausal patients
      with operable node positive stage II breast cancer. A prospective randomized
      national multicenter study.
AB  - AIMS: To evaluate possible differences in effect on time to recurrence and
      overall survival in node positive pre-menopausal breast cancer patients (age < or
      = 50 years) receiving LHRH analogue or tamoxifen as adjuvant endocrine treatment.
      METHODS: Between January 1989 and July 1994, 320 patients with node positive
      (pN(+)) and hormone receptor positive or receptor status unknown tumors were
      included and randomized in a national multicenter study to receive either
      tamoxifen or goserelin as adjuvant treatment for two years. Primary surgical
      treatment was employed according to current standards. Final follow-up was
      completed as of December 2000. Time to events were estimated by the Kaplan-Meier
      method, and compared by the log rank test. Relative risks were estimated by the
      Cox's proportional hazards model. RESULTS: No differences in time to first
      recurrence or overall survival were observed between treatment groups.
      Proportions of patients in each group having a second breast cancer were also
      similar. CONCLUSIONS: Standard adjuvant treatment with tamoxifen as compared to
      adjuvant LHRH analogue therapy employed in this group of breast cancer patients
      gave similar outcomes, but the number of patients was too small to formally
      exclude a potentially clinically relevant difference in survival.

PMID- 12217303
TI  - Knowledge of cancer symptoms among patients attending one-stop breast and rectal
      bleeding clinics.
AB  - AIM AND METHOD: The aim of this questionnaire study was to identify knowledge of
      breast and colorectal cancer symptoms among 100 patients attending one-stop
      breast clinics and rectal bleeding clinics and to determine the source of the
      information. RESULTS: Seventy-five breast clinic (mean age 46 years, all female)
      and 78 colorectal clinic patients (mean age 59 years, 51% male) responded.
      Knowledge of breast was significantly greater than bowel cancer in both groups
      (P<0.0001, McNemar's chi(2)). There was no difference in knowledge of symptoms of
      breast cancer or bowel cancer between patients attending either clinic. There was
      a positive association between cancer knowledge, family history and female gender
      but no association with age. Knowledge of Bowel Cancer Awareness Week was
      positively associated with colorectal cancer knowledge. CONCLUSION: Knowledge of
      colorectal cancer is much less than breast cancer in clinic attenders. Seventy
      five per cent of women attending breast clinic could name a breast cancer symptom
      whereas only 37% of patients attending colorectal clinic could name a bowel
      cancer symptom. These findings have implications when considering patients'
      anxiety, expectations of a cancer diagnosis and breaking bad news.

PMID- 12217304
TI  - Clinical outcome and bromodeoxyuridine derived proliferation indices in 100
      colonic and rectal carcinomas.
AB  - AIM: In vivo labelling of human colonic and rectal tumours with bromodeoxyuridine
      (BrdUrd) and analysis by flow cytometry (FCM) allows the labelling index (LI), S
      phase duration (Ts) and the potential doubling time (Tpot) of the tumour to be
      estimated in vivo. METHODS: The data for a series of 100 tumour specimens from 97
      patients with colonic and rectal carcinoma was reported in 1991, and correlated
      with Dukes' classification and histological differentiation. RESULTS: This study
      reports the eventual outcome of the 97 patients after 12 years. There were no
      significant associations between proliferation data of the index tumours and
      patient outcome. No adverse events were identified which could be attributed to
      the use of the halogenated pyrimidine label in vivo. CONCLUSION: Dynamic cell
      proliferation indices provide detailed information on the cell kinetics of
      colorectal tumours but these do not correlate with clinical prognostic markers or
      outcome.

PMID- 12217305
TI  - Acute normovolaemic haemodilution in colorectal surgery.
AB  - AIMS: Blood transfusions are often given to surgical patients. This study was
      designed to assess whether acute normovolaemic haemodilution (ANH) reduces
      exposure to allogeneic blood, affects clinical outcome and hospital stay, and is
      feasible in colorectal surgery. METHODS: All ASA 1 and 11 patients undergoing
      colectomies performed between 1997 and 1999 were identified retrospectively from
      our colorectal cancer database to ascertain our current peri and postoperative
      transfusion practice. Twenty-six selected patients subsequently underwent ANH
      during colectomy surgery. The number of patients and units transfused were
      identified. RESULTS: One hundred and twenty-three of 317 (39%) patients
      identified from our colorectal cancer database were transfused a total of 328
      units (median 2, range 1-7). Of the 26 patients undergoing ANH, 4 (15%) were
      transfused a total of 13 units (median 3, range 2-5). The reduction in number of
      patients transfused was statistically significant (P=0.017). ANH increased
      anaesthetic time by a median of 19 min. There were no complications associated
      with ANH and the median hospital stay was 9 days (range 6-13). CONCLUSIONS: In
      this pilot study of selected patients, ANH is a feasible and effective method of
      reducing allogeneic blood exposure in major colorectal surgery. A prospective
      randomised controlled trial is now urgently required.

PMID- 12217306
TI  - Adjuvant radiotherapy in resectable pancreatic carcinoma.
AB  - AIM: Pancreatic cancer is a near fatal disease. External beam radiotherapy and
      intraoperative radiation therapy (IORT) has been proposed with the aim to improve
      clinical outcome in resectable tumors. The aim of this study is to assess the
      feasibility and outcome in patients with cT1-3 pancreatic cancer, treated with
      surgery, external beam radiotherapy and IORT. METHODS: From 1990 to 1996, 17
      patients with clinical stage T1-3N0-1M0 adenocarcinoma of the head of the
      pancreas were treated with pancreatectomy and pre- (nine patients: 5 Gy), intra-
      (all patients: 10 Gy) and post-operative (all patients: 50 Gy) radiotherapy. The
      pathologic T stages were: 4 pT2 and 13 pT3. The pathologic N stages were: 9 pN0
      and 8 pN1. Minimum follow-up in living patients was 60 months. RESULTS: No
      perioperative mortalities were recorded. Two patients showed postoperative
      morbidity (11.8%) which required a subsequent laparotomy. The disease-free
      survival at 1, 3 and 5 years was 41, 23 and 18%, respectively (median: 9 months).
      The overall survival at 1, 3 and 5 years was 70%, 41% and 18%, respectively
      (median: 17.5 months). Three patients developed local failure (17.6%) and 12
      patients showed distant metastases (70.6%). Univariate analysis (logrank) showed:
      a significant correlation between both N-stage and retroperitoneal involvement
      (RPI) with local control (N-stage: P=0.0155; RPI:P =0.0295), a significant
      correlation between maximum tumor size and metastases-free survival (P=0.0167)
      and overall survival (P=0.0241); the female gender was another predictor of
      prolonged survival (P= 0.0465). Multivariate analysis (Cox) showed a significant
      impact of N-stage and retroperitoneal involvement on local control and also a
      significant correlation between perineural involvement and tumor diameter with
      metastases-free survival. CONCLUSIONS: These results are similar to those of
      other published series and suggest that this approach is feasible with acceptable
      local control and survival, especially in patients with small tumors (<2.5 cm: 5
      year survival=33.3%) and in female patients (5 year survival=30%). Due to the
      impact of gender, tumor diameter and N stage on prognosis, in the design of
      future trials a stratification of patients based on these categories should be
      considered. The search of effective chemotherapeutic agents is required, to
      reduce the high incidence of distant metastases, especially in larger tumors.

PMID- 12217307
TI  - A phase II single institutional experience with preoperative radiochemotherapy in
      pancreatic adenocarcinoma.
AB  - BACKGROUND: Resection of pancreatic adenocarcinoma has a limited impact on
      survival. We hypothesized that delivering preoperative radiochemotherapy (RTCT)
      might enhance local control of the cancer and improve survival. METHODS: Nineteen
      patients with localized pancreatic cancer (14 head and 5 body) were treated
      during the past 4 years with an intramural protocol consisting of continuous
      infusion of fluorouracile (5-FU: 650 mg/m(2)/D1-D5 and D21-D25 and Cisplatin 80
      mg/m(2)/bolus D2 and D22 with preoperative external beam radiotherapy (RT) (30Gy
      split course RT or 45 Gy standard fractionation RT). RESULTS: Four patients did
      not have surgical resection: Three patients were noted to have liver metastases
      and 1 patient developed peritoneal carcinomatosis. The remaining 15 patients had
      potentially curative resection (12 Whipple procedure and 3 distal subtotal
      pancreatectomy). There was no postoperative death. Pathologic findings showed
      five major responses including 2 patients with complete pathologic response. The
      overall median survival for the 19 study patients was 20 months. The median
      disease free and 2-year overall survival for the group with resection were 30
      months and 52.3%. CONCLUSIONS: Preoperative RTCT followed by resection is well
      tolerated and safe for patients with localized pancreatic cancer. Major
      histological response occurred for 25% of patients. This approach could offer
      improvement in patient survival.

PMID- 12217308
TI  - Value of computed tomography in addition to ultrasound for preoperative staging
      of gastric cancer.
AB  - AIM: The aim of this study was to assess the added value of computed tomography
      (CT) with ultrasound in identifying unresectable or incurable gastric cancer.
      METHODS: One hundred and eighteen patients with various types of gastric cancer
      were preoperatively staged with ultrasound and CT between January 1999 and
      October 2000. Each individual was evaluated for ascites, liver metastasis and
      peritoneal metastases. The observations were compared to findings at surgery.
      RESULTS: Both techniques were highly specific (93-99%) for all conditions except
      retroperitoneal invasion (85%). The sensitivities of ultrasound and CT were 64
      and 36% for ascites, 50 and 62% for liver metastasis, 9 and 13% for peritoneal
      metastasis and 18 and 41% for retroperitoneal invasion. Ultrasonography was more
      sensitive than CT for detecting ascites, and CT was better for detecting
      retroperitoneal invasion. CONCLUSIONS: Both techniques allowed more accurate
      identification of liver metastasis and ascites than peritoneal metastasis and
      retroperitoneal invasion. In order to simplify scanning of patients with gastric
      cancer, we recommend that CT investigation should be done only in cases where the
      ultrasound findings are suspicious.

PMID- 12217309
TI  - Stop-flow technique for loco-regional delivery of antiblastic agents: literature
      review and personal experience.
AB  - AIMS: The therapeutic approach for primary or recurrent advanced solid tumours,
      particularly when unresectable, is still one of the main medical challenges in
      the management of cancer patients. The stop-flow (SF) technique has been recently
      proposed as a semi-invasive drug delivery system based on the blood supply
      blockage of the tumour-bearing area. Here, we discuss the principles underlying
      the SF technique as well as the worldwide experience published so far. We also
      report on the results of our pilot study on pelvic and limb SF perfusion.
      METHODS: We reviewed the worldwide experience on SF as reported by the literature
      published on PubMed from 1990 through 2001. In our series, we treated 20 patients
      affected with locally advanced melanoma, soft tissue sarcoma or colorectal
      cancer. RESULTS: This therapeutic modality - at least for some tumours - can
      achieve encouraging results in terms of clinical response even after conventional
      therapies have failed. Moreover, as a safe and relatively simple procedure, SF
      can be applied to patients for whom traditional treatments (i.e. surgery,
      systemic chemotherapy) are contraindicated because of poor general conditions.
      CONCLUSIONS: At present, the SF technique should be considered an investigational
      approach to locally advanced cancers. The encouraging results obtained with this
      procedure should be validated by large phase III trials.

PMID- 12217310
TI  - From PCR to RCA: a surgical trainee's guide to the techniques of genetic
      amplification.
AB  - With the advent of evidence-based medicine and the Calman-Hine Report, more and
      more surgical trainees are undertaking a period of research, either before
      entering or during their Specialist Registrar training. Many will encounter
      concepts in science uncommon in daily clinical settings. This paper will
      elucidate the techniques of genetic amplification available today with their
      potential for usage in clinical research.

PMID- 12217311
TI  - How I do it--biopsy of axillary and internal mammary sentinel node for complete
      nodal staging in male breast cancer.

PMID- 12217312
TI  - No relationship between tumour infiltrating lymphocytes and overall survival is
      seen in malignant mesothelioma of the pleura.

PMID- 12217313
TI  - Re. The significance of intra-mammary nodes in primary breast cancer. Eur J Surg
      Oncol 2001; 27: 707-708.

PMID- 12217314
TI  - The Hox Paradox: More complex(es) than imagined.
AB  - An understanding of the origin of different body plans requires knowledge of how
      the genes and genetic pathways that control embryonic development have evolved.
      The Hox genes provide an appealing starting point for such studies because they
      play a well-understood causal role in the regionalization of the body plan of all
      bilaterally symmetric animals. Vertebrate evolution has been characterized by
      gene, and possibly genome, duplication events, which are believed to have
      provided raw genetic material for selection to act upon. It has recently been
      established that the Hox gene organization of ray-finned fishes, such as the
      zebrafish, differs dramatically from that of their lobe-finned relatives, a group
      that includes humans and all the other widely used vertebrate model systems. This
      unusual Hox gene organization of zebrafish is the result of a duplication event
      within the ray-finned fish lineage. Thus, teleosts, such as zebrafish, have more
      Hox genes arrayed over more clusters (or "complexes") than do tetrapod
      vertebrates. Here, I review our understanding of Hox cluster architecture in
      different vertebrates and consider the implications of gene duplication for Hox
      gene regulation and function and the evolution of different body plans.

PMID- 12217315
TI  - The mouse Kreisler (Krml1/MafB) segmentation gene is required for differentiation
      of glomerular visceral epithelial cells.
AB  - Molecular components of the glomerular filtration mechanism play critical roles
      in renal diseases. Many of these components are produced during the final stages
      of differentiation of glomerular visceral epithelial cells, also known as
      podocytes. While basic domain leucine zipper (bZip) transcription factors of the
      Maf subfamily have been implicated in cellular differentiation processes,
      Kreisler (Krml1/MafB), the gene affected in the mouse kreisler (kr) mutation, is
      known for its role in hindbrain patterning. Here we show that mice homozygous for
      the kr(enu) mutation develop renal disease and that Kreisler is essential for
      cellular differentiation of podocytes. Consistent with abnormal podocyte
      differentiation, kr(enu) homozygotes show proteinuria, and fusion and effacement
      of podocyte foot processes, which are also observed in the nephrotic syndrome.
      Kreisler acts during the final stages of glomerular development-the transition
      between the capillary loop and mature stages-and downstream of the Pod1 basic
      domain helix-loop-helix transcription factor. The levels of Podocin, the gene
      mutated in autosomal recessive steroid-resistant nephrotic syndrome (NPHS2), and
      Nephrin, the gene mutated in congenital nephrotic syndrome of the Finnish type
      (NPHS1), are slightly reduced in kr(enu)/kr(enu) podocytes. However, these
      observations alone are unlikely to account for the aberrant podocyte foot process
      formation. Thus, Kreisler must regulate other unknown genes required for podocyte
      function and with possible roles in kidney disease.

PMID- 12217317
TI  - Refinement of wingless expression by a wingless- and notch-responsive homeodomain
      protein, defective proventriculus.
AB  - Pattern formation during animal development is often induced by extracellular
      signaling molecules, known as morphogens, which are secreted from localized
      sources. During wing development in Drosophila, Wingless (Wg) is activated by
      Notch signaling along the dorsal-ventral boundary of the wing imaginal disc and
      acts as a morphogen to organize gene expression and cell growth. Expression of wg
      is restricted to a narrow stripe by Wg itself, repressing its own expression in
      adjacent cells. This refinement of wg expression is essential for specification
      of the wing margin. Here, we show that a homeodomain protein, Defective
      proventriculus (Dve), mediates the refinement of wg expression in both the wing
      disc and embryonic proventriculus, where dve expression requires Wg signaling.
      Our results provide evidence for a feedback mechanism that establishes the wg
      expressing domain through the action of a Wg-induced gene product.

PMID- 12217316
TI  - GATA proteins identify a novel ventral interneuron subclass in the developing
      chick spinal cord.
AB  - Members of the GATA transcription factor gene family have been implicated in a
      variety of developmental processes, including that of the vertebrate central
      nervous system. However, the role of GATA proteins in spinal cord development
      remains unresolved. In this study, we investigated the expression and function of
      two GATA proteins, GATA2 and GATA3, in the developing chick spinal cord. We show
      that both proteins are expressed by a distinct subpopulation of ventral
      interneurons that share the same dorsoventral position as CHX10-positive V2
      interneurons. However, no coexpression is observed between the two GATA proteins
      and CHX10. By in vivo notochord grafting and cyclopamine treatment, we
      demonstrate that the spatially restricted pattern of GATA3 expression is
      regulated, at least in part, by the signaling molecule Sonic hedgehog. In
      addition, we further show that Sonic hedgehog induces GATA3 expression in a dose
      dependent manner. Using in ovo electroporations, we also demonstrate that GATA2
      is upstream of GATA3 in the same epigenetic cascade and that GATA3 is capable of
      inducing GATA2 expression in vivo. Furthermore, the ectopically expressed GATA
      proteins can repress differentiation of other ventral cell fates, but not the
      development of progenitor populations identified by PAX protein expression. Taken
      together, our findings strongly suggest an important role for GATA2 and GATA3
      proteins in the establishment of a distinct ventral interneuron subpopulation in
      the developing chick spinal cord.

PMID- 12217318
TI  - Migrating mesoderm establish a uniform distribution of laminin in the developing
      grasshopper embryo.
AB  - The basal lamina is composed of molecules which physically interact to form a
      network that serves as a migrational scaffold for many cell types. In the
      developing peripheral nervous system of the grasshopper, neuronal growth cones
      are intimately associated with the basal lamina as they migrate. Laminin is a
      major component of the basal lamina and is a potent promoter of neurite outgrowth
      in vitro. However, it is unclear what the source of laminin is or how the
      distribution of laminin within the basal lamina is established. To address this
      question, grasshopper laminin subunit genes were cloned. As expected, laminin was
      found within the basal lamina throughout the embryo, in particular in the limb
      bud, where its expression is coincident with the outgrowth and guidance of the
      Tibial (Til) pioneer neurons. Surprisingly, the synthesis of beta and gamma
      chains of laminin was restricted to migratory mesodermal cells, while in other
      nonmigratory tissues, such as epithelium and presumptive muscle, beta and gamma
      chains of laminin were not detected. In spite of this, laminin immunoreactivity
      in the basal lamina appears uniform and is available as a substrate for axonal
      outgrowth.

PMID- 12217319
TI  - An essential role for functional telomeres in mouse germ cells during
      fertilization and early development.
AB  - Late generations of telomerase-null (TR(-/-)) mice exhibit progressive defects in
      highly proliferative tissues and organs and decreased fertility, ultimately
      leading to sterility. To determine effects of telomerase deficiency on germ
      cells, we investigated the cleavage and preimplantation development of embryos
      derived from both in vivo and in vitro fertilization of TR(-/-) or wild-type
      (TR(+/+)) sperm with either TR(-/-) or TR(+/+) oocytes. Consistently,
      fertilization of TR(-/-) oocytes with either TR(+/+) or TR(-/-) sperm, and TR(-/
      ) sperm with TR(+/+) oocytes, resulted in aberrant cleavage and development, in
      contrast to the normal cleavage and development of TR(+/+) oocytes fertilized by
      TR(+/+) sperm. Many (>50%) of the fertilized TR(-/-) eggs developed only one
      pronucleus, coincident with increased incidence of cytofragmentation, in contrast
      to the normal formation of two pronuclei and equal cleavage of wild-type embryos.
      These results suggest that both TR(-/-) sperm and oocytes contribute to defective
      fertilization and cleavage. We further found that a subset (7-9%) of telomeres
      was undetectable at the ends of some metaphase I chromosomes from TR(-/-)
      spermatocytes and oocytes, indicating that meiotic germ cells lacking telomerase
      ultimately resulted in telomere shortening and loss. Dysfunction of meiotic
      telomeres may contribute to aberrant fertilization of gametes and lead to
      abnormal cleavage of embryos, implying an important role of functional telomeres
      for germ cells undergoing fertilization and early cleavage development.

PMID- 12217320
TI  - Meiotic prophase abnormalities and metaphase cell death in MLH1-deficient mouse
      spermatocytes: insights into regulation of spermatogenic progress.
AB  - The MLH1 protein is required for normal meiosis in mice and its absence leads to
      failure in maintenance of pairing between bivalent chromosomes, abnormal meiotic
      division, and ensuing sterility in both sexes. In this study, we investigated
      whether failure to develop foci of MLH1 protein on chromosomes in prophase would
      lead to elimination of prophase spermatocytes, and, if not, whether univalent
      chromosomes could align normally on the meiotic spindle and whether metaphase
      spermatocytes would be delayed and/or eliminated. In spite of the absence of MLH1
      foci, no apoptosis of spermatocytes in prophase was detected. In fact,
      chromosomes of pachytene spermatocytes from Mlh1(-/-) mice were competent to
      condense metaphase chromosomes, both in vivo and in vitro. Most condensed
      chromosomes were univalents with spatially distinct FISH signals. Typical
      metaphase events, such as synaptonemal complex breakdown and the phosphorylation
      of Ser10 on histone H3, occurred in Mlh1(-/-) spermatocytes, suggesting that
      there is no inhibition of onset of meiotic metaphase in the face of massive
      chromosomal abnormalities. However, the condensed univalent chromosomes did not
      align correctly onto the spindle apparatus in the majority of Mlh1(-/-)
      spermatocytes. Most meiotic metaphase spermatocytes were characterized with
      bipolar spindles, but chromosomes radiated away from the microtubule-organizing
      centers in a prometaphase-like pattern rather than achieving a bipolar
      orientation. Apoptosis was not observed until after the onset of meiotic
      metaphase. Thus, spermatocytes are not eliminated in direct response to the
      initial meiotic defect, but are eliminated later. Taken together, these
      observations suggest that a spindle assembly checkpoint, rather than a
      recombination or chiasmata checkpoint, may be activated in response to meiotic
      errors, thereby ensuring elimination of chromosomally abnormal gamete precursors.

PMID- 12217321
TI  - Duplication of the Hoxd11 gene causes alterations in the axial and appendicular
      skeleton of the mouse.
AB  - The Hox genes encode a group of transcription factors essential for proper
      development of the mouse. Targeted mutation of the Hoxd11 gene causes reduced
      male fertility, vertebral transformation, carpal bone fusions, and reductions in
      digit length. A duplication of the Hoxd11 gene was created with the expectation
      that the consequences of restricted overexpression in the appropriate cells would
      provide further insight into the function of the Hoxd11 gene product. Genetic
      assays demonstrated that two tandem copies of Hoxd11 were functionally
      indistinguishable from the normal two copies of the gene on separate chromosomes
      with respect to formation of the axial and appendicular skeleton. Extra copies of
      Hoxd11 caused an increase in the lengths of some bones of the forelimb autopod
      and a decrease in the number of lumbar vertebrae. Further, analysis of the Hoxd11
      duplication demonstrated that the Hoxd11 protein can perform some functions
      supplied by its paralogue Hoxa11. For example, the defects in forelimb bones are
      corrected when extra copies of Hoxd11 are present in the Hoxa11 homozygous mutant
      background. Thus, it appears that Hoxd11 can quantitatively compensate for the
      absence of Hoxa11 protein, and therefore Hoxa11 and Hoxd11 are functionally
      equivalent in the zeugopod. However, extra copies of Hoxd11 did not improve male
      or female fertility in Hoxa11 mutants. Interestingly, the insertion of an
      additional Hoxd11 locus into the HoxD complex does not appear to affect the
      expression patterns of the neighboring Hoxd10, -d12, or -d13 genes.

PMID- 12217322
TI  - In vivo evidence that BMP signaling is necessary for apoptosis in the mouse limb.
AB  - To determine the role of Bone morphogenetic protein (BMP) signaling in murine
      limb development in vivo, the keratin 14 promoter was used to drive expression of
      the BMP antagonist Noggin in transgenic mice. Phosphorylation and nuclear
      translocation of Smad1/5 were dramatically reduced in limbs of the transgenic
      animals, confirming the inhibition of BMP signaling. These mice developed
      extensive limb soft tissue syndactyly and postaxial polydactyly. Apoptosis in the
      developing limb necrotic zones was reduced with incomplete regression of the
      interdigital tissue. The postaxial extra digit is also consistent with a role for
      BMPs in regulating apoptosis. Furthermore, there was persistent expression of
      Fgf8, suggesting a delay in the regression of the AER. However, Msx1 and Msx2
      expression was unchanged in these transgenic mice, implying that induction of
      these genes is not essential for mediating BMP-induced interdigital apoptosis in
      mice. These abnormalities were rescued by coexpressing BMP4 under the same
      promoter in double transgenic mice, suggesting that the limb abnormalities are a
      direct effect of inhibiting BMP signaling.

PMID- 12217323
TI  - Disruption of segmental neural crest migration and ephrin expression in delta-1
      null mice.
AB  - Neural crest cells migrate segmentally through the rostral half of each trunk
      somite due to inhibitory influences of ephrins and other molecules present in the
      caudal-half of somites. To examine the potential role of Notch/Delta signaling in
      establishing the segmental distribution of ephrins, we examined neural crest
      migration and ephrin expression in Delta-1 mutant mice. Using Sox-10 as a marker,
      we noted that neural crest cells moved through both rostral and caudal halves of
      the somites in mutants, consistent with the finding that ephrinB2 levels are
      significantly reduced in the caudal-half somites. Later, mutant embryos had
      aberrantly fused and/or reduced dorsal root and sympathetic ganglia, with a
      marked diminution in peripheral glia. These results show that Delta-1 is
      essential for proper migration and differentiation of neural crest cells.
      Interestingly, absence of Delta-1 leads to diminution of both neurons and glia in
      peripheral ganglia, suggesting a general depletion of the ganglion precursor pool
      in mutant mice.

PMID- 12217324
TI  - Differential requirements for shh in mammary tissue and hair follicle
      morphogenesis.
AB  - Sonic Hedgehog (Shh) is a secreted morphogen that directs patterning and cellular
      differentiation through binding to its receptor Patched (Ptc). It is required for
      the development of skin-derived organs, such as hair, whiskers, and teeth. The
      mammary gland is a skin-derived organ that develops mainly during adult life in
      which Shh is expressed from puberty to lactation. We have investigated the role
      of Shh in mammary gland morphogenesis and differentiation by two transplantation
      approaches. Since Shh-null fetuses die at late embryogenesis, we transplanted Shh
      null mammary anlagen into cleared fat pads and under the renal capsule of wild
      type host mice. Pregnancy-mediated functional differentiation of Shh-null mammary
      epithelium was indistinguishable from wild type transplants, while hair follicles
      derived from cotransplanted skin only developed in wild type transplants.
      Transplants of Ihh-null anlagen also developed normally. To assess the molecular
      consequences of Shh deletion in mammary tissue, we compared mRNA levels of
      patched 1, a target gene of Hedgehog signaling, in Shh-null and wild type mammary
      epithelial transplants. No reduction of Ptc1 transcripts was observed in Shh-null
      mammary tissues. Our results demonstrate that neither Shh nor Ihh is required for
      mammary gland morphogenesis and functional differentiation, suggesting that the
      two members of the Hedgehog family may have redundant function in activating the
      Ptc1 signaling pathway during mammary gland development.

PMID- 12217325
TI  - Tubedown-1 in remodeling of the developing vitreal vasculature in vivo and
      regulation of capillary outgrowth in vitro.
AB  - Tubedown-1 (tbdn-1) is a mammalian homologue of the N-terminal acetyltransferase
      subunit NAT1 of Saccharomyces cerevisiae and copurifies with an acetyltransferase
      activity. Tbdn-1 expression in endothelial cells becomes downregulated during the
      formation of capillary-like structures in vitro and is regulated in vivo in a
      manner which suggests a functional role in dampening blood vessel development.
      Here we show that tbdn-1 is expressed highly in the vitreal vascular network
      (tunica vasculosa lentis and vasa hyaloidea propria) during the pruning and
      remodeling phases of this transient structure. The vitreal blood vessels of mice
      harboring a targeted inactivation of TGF-beta2 fail to remodel and abnormally
      accumulate, a phenomenon reminiscent of the ocular pathology resembling
      persistent fetal vasculature (PFV) in humans. Since suppression of normal tbdn-1
      expression has been previously observed in retinal vessel proliferation, we
      analyzed vitreal vascular changes and tbdn-1 expression in TGF-beta2(-/-) eyes.
      The nuclei of vitreal vessel endothelial cells in TGF-beta2(-/-) eyes express
      proliferating cell nuclear antigen (PCNA) and exhibit increased levels of active
      (P42/44)mitogen-activated protein kinase (phospho-(P42/44)MAPK), characteristics
      consistent with proliferative endothelial cells. In contrast to normal vitreal
      vessels, collagen IV expression exhibited a disorganized pattern in the TGF
      beta2(-/-) vitreal vessels, suggesting vessel disorganization and possibly a
      breakdown of vessel basal laminae. Moreover, vitreal vessels of TGF-beta2(-/-)
      mice lack expression of pericyte markers (CD13, alpha smooth muscle actin) and
      show ultrastructural changes consistent with pericyte degeneration. The
      accumulating vitreal blood vessels of TGF-beta2(-/-) mice, while maintaining
      expression of the endothelial marker von Willebrand Factor, show a significant
      decrease in the expression of tbdn-1. We addressed the functional role of tbdn-1
      in the regulation of vitreal blood vessels using an in vitro model of choroid
      retina capillary outgrowth. Clones of the RF/6A fetal choroid-retina endothelial
      cell line showing suppression of tbdn-1 levels after overexpression of an
      antisense TBDN-1 cDNA display a significant increase in the formation of
      capillary-like structures in vitro compared with controls. These findings suggest
      that tbdn-1 inhibits capillary-like formation in vitro and may serve to dampen
      vitreal blood vessel formation preceding the regression of the vitreal
      vasculature during development. Our results also suggest that tbdn-1 may
      participate with TGF-beta2 in regulating normal development of the vitreal
      vasculature.

PMID- 12217326
TI  - Multiple Cdk1 inhibitory kinases regulate the cell cycle during development.
AB  - The Wee kinases block entry into mitosis by phosphorylating and inhibiting the
      activity of the mitotic cyclin-dependent kinase, Cdk1. We have found that the
      various Xenopus Wee kinases have unique temporal and spatial patterns of
      expression during development. In addition, we have isolated and characterized a
      new Wee1-like kinase, Xenopus Wee2. By both in vivo and in vitro tests, Xenopus
      Wee2 functions as a Wee1-like kinase. The previously isolated Wee1-like kinase,
      Xenopus Wee1, is expressed only as maternal gene product. In contrast, Xenopus
      Wee2 is predominantly a zygotic gene product, while the third Wee kinase, Xenopus
      Myt1, is both a maternal and zygotic gene product. Concurrent with the changing
      levels of these Cdk inhibitory kinases, the pattern of embryonic cell division
      becomes asynchronous and spatially restricted in the Xenopus embryo.
      Interestingly, once zygotic transcription begins, Xenopus Wee2 is expressed in
      regions of the embryo that are devoid of mitotic cells, such as the involuting
      mesoderm. In contrast, Xenopus Myt1 is expressed in regions of the embryo that
      have high levels of proliferation, such as the developing neural tissues. The
      existence of multiple Wee kinases may help explain how distinct patterns of cell
      division arise and are regulated during development.

PMID- 12217328
TI  - Hypogammaglobulinemia: fifty years later.

PMID- 12217327
TI  - N-twist, an evolutionarily conserved bHLH protein expressed in the developing
      CNS, functions as a transcriptional inhibitor.
AB  - Members of the basic helix-loop-helix (bHLH) transcription factor family play an
      essential role in multiple developmental processes. During neurogenesis, positive
      and negative regulation by bHLH proteins is essential for proper development.
      Here we report the identification and initial characterization of the bHLH gene,
      Neuronal twist (N-twist), named for its neural expression pattern and high
      sequence homology and physical linkage to the mesodermal inhibitor, M-twist. N
      twist is expressed in the developing mouse central nervous system in the
      midbrain, hindbrain, and neural tube. This neural expression is conserved in
      invertebrates, as expression of the Drosophila ortholog of N-twist is also
      restricted to the central nervous system. Like other bHLH family members, N-Twist
      heterodimerizes with E protein and binds DNA at a consensus bHLH-binding site,
      the E box. We show that N-Twist inhibits MASH1-dependent transcriptional
      activation by sequestering E protein in a dominant negative fashion. Thus, these
      studies support the notion that N-Twist represents a novel negative regulator of
      neurogenesis.

PMID- 12217329
TI  - The potential for gene therapy in the treatment of autoimmune disease.

PMID- 12217330
TI  - IL-4 induces IL-6 and signs of allergic-type inflammation in the nasal airways of
      nonallergic individuals.
AB  - In addition to its more widely recognized role in promoting IgE synthesis, we
      speculate that interleukin-4 (IL-4) may modulate both allergic- and nonallergic
      type inflammatory processes in the airway mucosa. We examined in vivo the effect
      of IL-4 on granulocyte and cytokine homeostasis in the nasal airways of
      nonallergic volunteers. Ten (N = 10) healthy subjects received nasal IL-4 (10
      microg) or saline (0.9%) challenges on separate occasions. Nasal lavage was
      obtained before and 24 h after nasal challenges. We report that IL-4 induced a
      significant increase in IL-6 and produced elevated levels of eosinophils and
      neutrophils compared to saline. These data demonstrate that IL-4 can modulate
      both allergic- and nonallergic-type inflammatory responses in the nasal airways
      of nonallergic individuals.

PMID- 12217331
TI  - Clinical, immunological, and molecular analysis in a large cohort of patients
      with X-linked agammaglobulinemia: an Italian multicenter study.
AB  - A questionnaire-based retrospective clinical and immunological survey was
      conducted in 73 males with a definite diagnosis of X-linked agammaglobulinemia
      based on BTK sequence analysis. Forty-four were sporadic and 29 familial cases.
      At December 2000, the patients' ages ranged from 2 to 33 years; mean age at
      diagnosis and mean duration of follow-up were 3.5 and 10 years respectively.
      After the mid-1980s all but 2 were on intravenous immunoglobulin (IVIG)
      substitution therapy, with residual IgG >500 mg/dl in 94% of the patients at the
      time of enrollment. Respiratory infections were the most frequent manifestation
      both prior to diagnosis and over follow-up. Chronic lung disease (CLD) was
      present in 24 patients, in 15 already at diagnosis and in 9 more by 2000. The
      cumulative risk to present at diagnosis with CLD increased from 0.17 to 0.40 and
      0.78 when the diagnosis was made at the ages of 5, 10, and 15 years respectively.
      For the 9 patients who developed CLD during follow-up, the duration of follow-up,
      rather than age at diagnosis; previous administration of intramuscular
      immunoglobulin; and residual IgG levels had a significant effect on the
      development of CLD. Chronic sinusitis was present in 35 patients (48%), in 15
      already at diagnosis and in 20 by 2000. Sistemic infections such as sepsis and
      meningitis/meningoencephalitis decreased over follow-up, probably due to optimal
      protection provided by high circulating IgG levels reached with IVIG.

PMID- 12217332
TI  - European surveillance of immunoglobulin safety--results of initial survey of 1243
      patients with primary immunodeficiencies in 16 countries.
AB  - A European multicenter study was conducted to obtain information on the current
      practices of immunoglobulin administration, the policies in use for the
      surveillance of the risk of hepatitis C virus (HCV) transmission, and the natural
      history of HCV infection in patients with hypogammaglobulinemia. Data from 1243
      patients with primary immunodeficiencies in 16 countries demonstrated that 90% of
      patients with antibody deficiencies receive intravenous immunoglobulins in an
      inpatient setting, and 7% of patients are treated with subcutaneous
      immunoglobulins, mainly at home. Wide variations have been reported regarding the
      frequency and the type of tests monitored for the surveillance on the risk of
      viral hepatitis transmission. Only 60% of patients have been tested at least once
      for HCV RNA detection. Data from 71 HCV-infected patients demonstrated a rapid
      progression of HCV infection, with end-stage liver disease, in about 40% of
      patients. Ten percent of patients spontaneously cleared the virus, and about 30%
      are asymptomatic. Patients with CVID have a worse prognosis than patients with
      XLA.

PMID- 12217333
TI  - Express subcutaneous IgG infusions: decreased time of delivery with maintained
      safety.
AB  - The aims of the study were to evaluate the safety and feasibility of weekly
      express subcutaneous replacement IgG self-infusions (E-SCIG, 35 mL/h/syringe
      driver) in 50 patients and to evaluate their perceptions of the therapy. A total
      of 4900 E-SCIG infusions at separate infusion sites were given on 1228 treatment
      occasions. The most commonly reported local tissue reactions were swelling (n =
      37), redness (n = 25), and soreness (n = 24). A majority of these patients
      reported the local reactions as less intense or unchanged compared to those
      arising from rapid SCIG (20 mL/h) infusions. The patients reported a median score
      of 16 (visual analogue scale, VAS; 1, not troublesome at all) regarding their
      overall perceptions of the local reactions. They were positive toward the home
      therapy regime (median VAS score 96; 100, very positive) and anxious to continue
      with the E-SCIG infusions (median VAS score 98; 100, very anxious). The E-SCIG
      method seems to be safe, with few pronounced local reactions, and is appreciated
      by the patients. Express delivery could also potentially facilitate IgG delivery
      in a wide variety of diseases, such as autoimmune and autoimmune-like conditions
      of a neurological or rheumatological character.

PMID- 12217334
TI  - Effective antiretroviral therapy reduces degradation of tryptophan in patients
      with HIV-1 infection.
AB  - Antiretroviral therapy (ART) has a significant impact on HIV-1 RNA levels, the
      CD4 cell count, and immune activation. We examined whether these changes are
      associated with a change in the rate of tryptophan degradation (expressed as the
      kynurenine to tryptophan ratio, kyn/trp) as an estimate for the activity of
      interferon-gamma inducible enzyme indoleamine (, )-dioxygenase (IDO). Plasma
      levels of tryptophan, kynurenine, and neopterin were measured pretherapy and 6
      months postinitiation of therapy in 45 patients with HIV-1 RNA levels of less
      than 1000 copies/ml 6 months after initiation of ART. Before ART, the patients
      had decreased tryptophan and increased kynurenine concentrations compared to
      healthy controls. During ART, average tryptophan levels increased; in the same
      time kynurenine and kyn/trp decreased (P < 0.001), although not to normal levels.
      Since pretherapy tryptophan concentrations correlated inversely with neopterin,
      and kynurenine correlated with viral load and neopterin but not with CD4 cell
      count, the data support the view that HIV production may induce immune activation
      and consequently tryptophan is degraded at a higher rate. In agreement, kyn/trp
      positively correlated with neopterin (r(s) = 0.60, P < 0.001), with virus load
      (r(s) = 0.37, P = 0.013), and very weakly with CD4(+) cells counts (r(s) = 0.30,
      P = 0.049). The change in the kyn/trp ratio during ART correlated more strongly
      with the change in neopterin levels (r(s) = 0.49, P = 0.001) than with the change
      in HIV RNA levels and weakly with the CD4 cell count. The data underscore the
      fact that both neopterin production and tryptophan degradation are triggered by
      immune activation. Tryptophan degradation is increased in HIV infection and
      partially reversed under ART. The data agree with the concept that immune
      activation is the common background of IDO activation which may be an important
      factor underlying T-cell hyporesponsiveness.

PMID- 12217335
TI  - Effects of extracorporeal photoimmunotherapy on soluble IL-2Ralpha, TNF-RI, and
      CD8 in patients with steroid-resistant acute graft-versus-host disease.
AB  - Extracorporeal photoimmunotherapy (ECP) has been successfully used as adjunct
      treatment for steroid-resistant graft-versus-host disease (GvHD) after allogeneic
      stem cell transplantation. We serially investigated serum levels of soluble
      interleukin-2 receptor-alpha (sIL-2Ralpha), soluble tumor necrosis factor
      receptor I (sTNF-RI), and soluble CD8 (sCD8) in 19 patients with steroid
      resistant acute GvHD before and after each ECP treatment. Highest levels of sIL
      2Ralpha and sTNF-RI correlated with severe acute GvHD and infections. Despite an
      immediate sIL-2Ralpha and sTNF-RI decrease after each treatment cycle, a mean
      surge of sTNF-RI>sIL-2Ralpha during the first three ECP cycles was observed in
      infections. A delayed surge, i.e., after the third ECP cycle, of sIL-2Ralpha and
      elevated post-ECP sCD8 levels was observed in patients developing chronic GvHD.
      While levels of sIL-2Ralpha and sTNF-RI correlate with the severity of acute GvHD
      and infections during the early ECP treatment period, the recurring increase of
      post-ECP sCD8 possibly may serve as parameter for developing chronic GvHD.

PMID- 12217336
TI  - Anti-CD200R ameliorates collagen-induced arthritis in mice.
AB  - Immunization of DBA/1 with 100 microg bovine collagen type II emulsified in
      Freund's adjuvant, followed by booster injection in incomplete adjuvant at 18
      days, leads to development of arthritis in more than 70% of mice by 28 days
      postinjection. We have previously shown that the novel immunosuppressant molecule
      CD200Fc (linking an extracellular domain of CD200 with a murine IgG2a Fc region)
      can suppress induction of disease when given to mice from the time of collagen
      injection. This occurs in concert with a decrease in the serum levels of anti
      collagen IgG ( approximately 50% reduction), with relatively more IgG2b and IgG3,
      decreased serum levels of TNFalpha and IFN-gamma, and decreased production of
      those same cytokines after restimulation of lymphocytes in vitro with collagen.
      Since CD200 induces suppression following engagement of a receptor (CD200R),
      known to be expressed on, among other cells, macrophages, we investigated whether
      infusion of anti-CD200R and/or CD200Fc would ameliorate established disease in
      DBA mice, when injections were begun following collagen immunization. Our data
      indicate an arrest of disease following either treatment, with modification of a
      number of immune parameters (serum and lymphocyte cytokine production) consistent
      with a general role for CD200:CD200R interactions in the regulation of induction
      and/or expression of autoimmune disorders. When a higher dose (250 microg/mouse)
      of anti-CD200R was infused into a group of overtly arthritic mice, a significant
      ( approximately 50%) decrease in arthritic joint score occurred over the 4-week
      treatment period.

PMID- 12217337
TI  - Chlamydophila pneumoniae infection of human aortic endothelial cells induces the
      expression of FC gamma receptor II (FcgammaRII).
AB  - Chronic endothelial infection is believed to be one of the factors able to cause
      endothelial cell damage and trigger the onset of human atherosclerosis.
      Chlamydophila pneumoniae infects endothelial cells and has received special
      attention because of both epidemiological and experimental evidence supporting
      its role as a risk factor for atherosclerosis. It is also possible that otherwise
      independent risk factors for atherosclerosis may have synergistic effects. Immune
      phenomena, such as the formation of circulating immune complexes (IC) containing
      modified LDL and corresponding antibodies, have been linked to the development of
      coronary artery disease. The antibodies involved in the immune response to
      modified lipoproteins are predominantly of the pro-inflammatory IgG1 and IgG3
      subclasses. However, it is difficult to understand how circulating IC could cause
      endothelial damage and initiate the atherosclerotic process, unless they were
      formed in the subendothelial space or immobilized by endothelial cells. The last
      hypothesis would be possible if endothelial cells expressed Fcgamma receptors.
      Healthy endothelial cells do not express Fcgamma receptors, but endothelial cells
      infected by a variety of infectious agents do. Thus we decided to investigate
      whether infection of endothelial cells with C. pneumoniae is also able to cause
      the expression of Fcgamma receptors. The expression of Fcgamma receptors (CD64,
      32, and 16) on human aortic endothelial cells infected with C. pneumoniae for 4,
      24, 36, and 48 h was studied by flow cytometry. Twenty-four hours after infection
      30-40% of the endothelial cells had detectable inclusion bodies, 8-9% of the
      total number of cells (approximately 25% of the infected cells) expressed
      FcgammaRII, and about 1.5-2% (5% of infected cells) expressed FcgammaRI and
      FcgammaRIII. Double-staining studies confirmed that the expression of FcgammaRII
      was limited to C. pneumoniae-infected endothelial cells. We conclude that C.
      pneumoniae infection induces primarily the expression of FcgammaRII by
      endothelial cells and this may be a significant link between two proposed
      pathogenic mechanisms involved in the pathogenesis of human atherosclerosis.

PMID- 12217338
TI  - Established T(H1) granulomatous responses induced by active Mycobacterium avium
      infection switch to T(H2) following challenge with Schistosoma mansoni.
AB  - Mycobacterium avium established a systemic infection with granulomatous
      inflammation in mice. Mice chronically infected with M. avium and subsequently co
      infected with Schistosoma mansoni developed additional, but morphologically
      distinct, hepatic granulomas. Schistosome eggs were not deposited in the spleen,
      and splenic granulomas in co-infected mice contained mycobacteria. In complete
      contrast to the T(H1) cytokine pattern observed with granuloma lymphocytes from
      M. avium-infected mice, granuloma lymphocytes from co-infected mice stimulated
      with PPD elaborated IL-4, but not IFN-gamma. Furthermore, mycobacterial
      granulomas in concurrently infected mice contained large numbers of eosinophils,
      a feature never seen in granulomas of M. avium-infected mice. Serum IgG1 and IgE
      levels in concurrently infected mice were significantly higher, but IgG2a levels
      significantly lower, than those in M. avium-infected mice, further evidence that
      the T(H1) component induced by M. avium is modulated subsequent to co-infection
      with S. mansoni. The dominance of the T(H2) response observed in this model could
      have clinical implications in areas where parasites and mycobacteria co-exist.

PMID- 12217339
TI  - A subset of CD8 memory T cells from old mice have high levels of CD28 and produce
      IFN-gamma.
AB  - Using carboxyfluorescein diacetate succinimidyl ester (CFSE)-tagged cells to
      measure proliferation in vivo, we found that only memory CD8(+) cells from mice
      older than 18 months gave measurable levels of proliferation and that the
      proportion of memory CD8(+) T cells able to proliferate in a nonirradiated
      recipient increased with age. CD8 cells that had proliferated in vivo contained
      higher levels of CD28 when compared to CD8 cells that had not divided. Cells with
      high levels of CD28 were preferentially able to divide in nonirradiated
      recipients. Using ex vivo intracellular staining analysis, we determined that
      most of the CD8(+) T cells that were capable of dividing in vivo produced IFN
      gamma after isolation from recipient mice or their original host. These studies
      thus document the presence in aged mice of a population of CD28(hi) CD8(+) cells
      whose ability to proliferate in vivo without antigenic stimulation and to produce
      IFN-gamma may be involved in immune regulation.

PMID- 12217340
TI  - B cell stimulatory effects of alpha-enolase that is differentially expressed in
      NZB mouse B cells.
AB  - Intrinsic polyclonal B cell activation is characteristic of NZB mice and it
      contributes to the development of lupus nephritis in NZB crosses. Although
      multiple autosomal genes appear to be involved, the major loci for B cell
      hyperactivity have been mapped on chromosome 4. To identify various genes
      determining B cell hyperactivity, differential mRNA display was done comparing B
      cells of NZB and BALB/c mice. The approach yielded 32 genes that were
      consistently upregulated in NZB B cells. Among these, alpha-enolase, which is
      located in the region of chromosome 4 containing B cell hyperactivity loci, was
      found to be spontaneously overexpressed only in NZB B cells, but not in splenic B
      or T cells of BALB/c or T cells of NZB mice. Exposure to soluble, but not plate
      bound, enolase induced splenic B cells from normal BALB/c mice or B cell lymphoma
      lines to secrete Ig that was mediated by augmented transcription. Moreover, in
      combination with a subthreshold stimulus with anti-IgM, enolase augmented the
      expression of CD69 and B7.2 in nai;ve B cells from normal mice. Enolase probably
      functions intracellularly as an accessory molecule in stimulating B cells. Since
      functionally related genes tend to congregate, enolase may contribute to
      polyclonal B cell activation in cooperation with other genes in the hyperactivity
      loci, which appear to be in a transcriptionally active region in NZB B cells.

PMID- 12217341
TI  - Live oral poliovirus vaccines and simian cytomegalovirus.
AB  - Live oral poliovirus vaccines (OPV) are often produced in primary Cercopithecus
      monkey kidney (CMK) cells. The kidneys of these monkeys are often latently
      infected with simian cytomegalovirus (SCMV), and CMK cultures are frequently
      contaminated with SCMV. We tested human, monkey and rabbit tissue culture
      systems, and found that MRC-5 cells are most sensitive for detection of SCMV. To
      address the question of whether OPV could be contaminated with infectious SCMV,
      we inoculated MRC-5 cells with neutralized OPV manufactured in the United States
      between 1972 and 1998. Infectious SCMV was not found in any of the vaccine lots
      tested. We also used the polymerase chain reaction (PCR) to search for SCMV DNA
      in live oral poliovirus vaccines; SCMV DNA sequences were found in several of the
      vaccine lots manufactured prior to 1992.

PMID- 12217342
TI  - Thermal stability: a means to assure tertiary structure in therapeutic proteins.
AB  - To be both safe and effective, a therapeutic product must have the correct
      chemical structure and be free of harmful contaminants. Structure in protein
      therapeutic products, however, implies not only the correct sequence of amino
      acids (primary structure) but also the proper folding of that amino acid chain in
      three-dimensional space (tertiary structure). This work is part of a general
      strategy to develop a battery of physico-chemical methods that could give
      assurances of structure (and hence function) in formulated therapeutic proteins
      in the absence of in vivo data. It focuses on recombinant human growth hormone
      (rhGH), a well-characterized therapeutic protein, and examines the utility of
      thermodynamic parameters in assessing its tertiary structure. Resistance of
      solutions of formulated rhGH to thermal denaturation was followed using Fourier
      Transform Infrared Spectroscopy (FTIR) by observing decreases in total helicity
      and increases in intermolecular beta-sheet formation. Under conditions known to
      induce changes in the intra-molecular ionic and H-bonding patterns stabilizing
      the tertiary structure but not affecting the protein's secondary structure or
      global fold, we have observed upwards of a 12 degrees C shift in the melting
      temperature of the protein. Furthermore, our results indicated that the T(m) of
      unfolding of rhGH was sensitive to much more subtle changes in the protein
      structure. Thus, resistance to thermal denaturation may well be a useful means to
      measure structure in formulations of well-characterized therapeutic proteins.

PMID- 12217343
TI  - Purity of spiking agent affects partitioning of prions in plasma protein
      purification.
AB  - Prions are not detectable in the blood or plasma of persons afflicted with
      classical or variant Creutzfeldt-Jakob disease, and they have never been shown to
      be transmitted by blood or plasma products. Despite the uncertainty as to the
      presence and biophysical properties of prions in plasma, prion removal studies
      have been conducted using brain homogenate or microsomes prepared from prion
      infected rodent brains as model prions. In this study, we compare the
      partitioning of different prion spiking agents, having different biophysical
      properties, in the processes used for plasma protein purification. We have found
      that membrane-bound prion spiking agents partition similarly, whereas purified,
      unbound pathogenic prion proteins can have significantly different partitioning
      properties depending on the conditions in the production process. We conclude
      that prion spiking studies for the evaluation of prion reduction in plasma
      protein purification should employ spiking agents with different biophysical
      properties to mimic partitioning of the theoretical prion contaminant. This will
      give greater assurance as to the prion safety margins of the life-saving plasma
      protein therapeutics and excipients.

PMID- 12217344
TI  - Comparable virus inactivation by bovine or vegetable derived Tween 80 during
      solvent/detergent treatment.
AB  - A mixture of Tri-n-butyl phosphate (TNBP) and Polysorbate 80 (Tween 80) is often
      used for virus inactivation during the manufacture of medicinal products derived
      from human plasma. This procedure, known as solvent/detergent treatment, is of
      high effectiveness for inactivation of enveloped viruses. Tween 80 can be
      manufactured from bovine tallow or from vegetable material. As the bovine-derived
      Tween 80 is normally used for the solvent/detergent treatment, the question has
      been raised whether vegetable-derived Tween 80 can be applied as an alternative
      substance for the solvent/detergent treatment. Comparable inactivation studies
      were therefore performed using Vesicular Stomatitis Virus (VSV),
      Pseudorabiesvirus (PRV), Semliki Forest Virus (SFV) and Bovine Diarrhoea Virus
      (BVDV). In principle, no differences were observed in the effectiveness of the
      solvent/detergent treatment when bovine or vegetable-derived Tween 80 was used.
      The comparability in the efficiency of both detergents for virus inactivation was
      shown to be independent of solvent/detergent concentration, of temperature (16
      degrees C and 6 degrees C vs. 27 degrees C and 25 degrees C) and protein
      concentration (10% and 5% human albumin). In summary, vegetable-derived Tween 80
      is of the same effectiveness as bovine-derived Tween 80, when used for virus
      inactivation by the solvent/detergent treatment.

PMID- 12217345
TI  - Effective use of gamma irradiation for pathogen inactivation of monoclonal
      antibody preparations.
AB  - Gamma irradiation has been used for decades as an effective method of pathogen
      inactivation of relatively inert materials. Until recently, its application to
      biologicals has resulted in unacceptable losses in functional activity. In this
      report we demonstrate that the damaging secondary effects of gamma irradiation
      can be controlled while maintaining the pathogen inactivation properties due to
      damage by primary effects. Control is achieved by a combination of protection
      from free radical damage to a monoclonal antibody through the use of the
      antioxidant ascorbate and by freeze-drying to minimize the potential for
      generating free radicals. The data demonstrate a synergy of these two approaches
      that results in quantitative recovery of functional activity while maintaining
      the ability to inactivate greater than 5 logs of porcine parvovirus infectivity.

PMID- 12217346
TI  - Physicochemical methods for predicting the biological potency of recombinant
      follicle stimulating hormone: an international collaborative study of isoelectric
      focusing and capillary zone electrophoresis.
AB  - Two methods for predicting the specific in vivo bioactivity of recombinant
      follicle stimulating hormone (FSH), based on quantitative measures of isoform
      distribution by isoelectric focusing (IEF)(1) and by capillary zone
      electrophoresis (CZE)(2) respectively, have been subjected to an international
      collaborative study by six laboratories from six countries. Both methods were
      used to estimate the predicted bioactivities of four preparations of follitropin
      beta, coded FSH A-D, differing widely in their isoform compositions and specific
      bioactivities. The mean predicted estimate of potency by IEF and CZE for each FSH
      preparation by each laboratory was within 80-125% of its potency estimated by
      bioassay, except for the mean estimates by CZE of that for FSH A by one
      laboratory and of that of FSH D by another. Each of the six laboratories using
      the IEF method, and each of the five laboratories using the CZE method were able
      to rank these FSHs according to their bioactivities, namely FSH B>FSH C>FSH A>FSH
      D. All laboratories were able to use both IEF and CZE to discriminate between FSH
      A and C, with bioactivities within 76-132% of one another. Four of six
      laboratories were able to use IEF, and two of five laboratories were able to use
      CZE, to discriminate between FSH B and C, with bioactivities within 89-112% of
      one another. This suggests that the accuracy and precision of both these methods
      should be sufficient to discriminate between FSHs which would meet or fail
      European Pharmacopoeia requirements for this type of hormone, since these
      stipulate that estimates of potency should fall between 80-125% of its stated
      potency. Using in most cases duplicate estimates in two independent assays, and
      excluding Laboratory 4, the pooled intra-laboratory geometric coefficient of
      variation (GCV) was about 4% for both IEF and CZE, and the inter-laboratory GCV
      was about 7% for IEF and about 10% for CZE. The use of one FSH preparation as a
      standard, with its specific activity as an assigned value, reduced the inter
      laboratory variability of estimates for the remaining FSHs by both methods. This
      increased the accuracy of the predicted estimates of bioactivity for these
      remaining FSHs in terms of their approximation to the values for their
      bioactivities estimated by bioassay. These data therefore suggest that both these
      methods, and particularly IEF, are sufficiently accurate, precise and robust to
      be used for predicting the bioactivity of batches of follitropin beta, and
      especially if used with a standard preparation.

PMID- 12217347
TI  - Usefulness of glycopeptide mapping by liquid chromatography/mass spectrometry in
      comparability assessment of glycoprotein products.
AB  - We previously reported on glycopeptide mapping of erythropoietin (EPO) by liquid
      chromatography/mass spectrometry (LC/MS). Using this method, glycopeptides in
      proteolytic digestion can be eluted before peptides, and are further separated on
      the basis of the carbohydrate structure. The detailed glycosylation at each
      glycosylation site can be elucidated based on mass chromatography and mass
      spectroscopy. In this study, we evaluated glycopeptide mapping with regard to its
      use in comparability assessment of glycoprotein products possessing multiple
      glycosylation sites. Models of closely related glycoprotein products used in this
      study are EPOs produced from three different sources. We previously reported that
      there are differences in the carbohydrate heterogeneity of these EPOs with regard
      to sialylation, acetylation, and sulphation patterns, using sugar mapping by
      LC/MS. In this paper, we demonstrated that glycopeptide mapping can distinguish
      site-specific glycosylation among these three EPOs and reveal the differences in
      acetylation, sialylation, and sulphation at each glycosylation site in one
      analysis. Our method can thus be useful in comparability assessment of
      therapeutic glycoproteins in terms of glycosylation.

PMID- 12217348
TI  - Comparison of two in vitro methods for the measurement of recombinant human TSH
      bioactivity.
AB  - Thyroid stimulating hormone (TSH), a pituitary glycoprotein hormone, is a potent
      inducer of intracellular cAMP production. Two methods for measuring TSH
      bioactivity were evaluated and compared. One assay is based on using a
      radioimmunoassay (RIA) to measure the recombinant human TSH-induced increase in
      cAMP using a bovine thyroid membrane isolate. The other is based on a Chinese
      hamster ovary (CHO) cell line that has been transfected with the TSH receptor and
      a cAMP-responsive luciferase reporter. The within-assay coefficient of variation
      for the membrane-based assay was determined to be approximately 35% compared with
      approximately 25% for the cell-based assay. Twenty-one preparations of
      recombinant human TSH (rhTSH) were tested using both methods. No significant
      difference was detected between the data sets and no assay bias was present. Both
      assay systems provide a suitable means for measuring the activity of rhTSH. The
      advantage of the membrane-based assay is the relatively small quantity of TSH
      needed for analysis. However, the average time required to analyse a sample using
      the membrane-based method was more than twice as long as that needed to test a
      sample in the cell-based assay. Other advantages of the cell-based method include
      the use of a 96-well format, which facilitates the analysis of several
      concentrations of rhTSH within one assay plate, and the use of a non-radioactive
      endpoint.

PMID- 12217349
TI  - Effect of sample storage conditions on virus inactivation by solvent/detergent.

PMID- 12217351
TI  - Protease inhibitors: synthesis of matrix metalloproteinase and bacterial
      collagenase inhibitors incorporating 5-amino-2-mercapto-1,3,4-thiadiazole zinc
      binding functions.
AB  - Matrix metalloproteinase (MMP)/bacterial collagenase inhibitors incorporating 5
      amino-2-mercapto-1,3,4-thiadiazole zinc binding functions are reported. A series
      of compounds was prepared by reaction of arylsulfonyl isocyanates or arylsulfonyl
      halides with phenylalanyl-alanine, followed by coupling with 5-amino-2-mercapto
      1,3,4-thiadiazole in the presence of carbodiimides. These new compounds were
      assayed as inhibitors of human MMP-1, MMP-2, MMP-8 and MMP-9, and of the
      collagenase isolated from the anaerobe Clostridium histolyticum (ChC). The new
      derivatives proved to be powerful inhibitors of these metalloproteases, with
      activities in the low micromolar range for some of the target enzymes, depending
      on the substitution pattern at the arylsulfonyl(ureido) moieties.

PMID- 12217350
TI  - Analogues of aspartic proteases synthesized by densely covering silica gel with
      carboxyl groups.
AB  - Aspartic protease analogues synthesized by covering the surface of silica gel
      with carboxyl groups effectively hydrolyzed hemoglobin and gamma-globulin. It is
      proposed that the carboxyl group is involved in both complexation of the protein
      substrate and the catalytic cleavage of the peptide bonds of the complexed
      proteins.

PMID- 12217352
TI  - Structural assignment of 2,6- and 2,7-disubstituted naphthalenes and prediction
      of (13)C nuclear magnetic resonance chemical shifts: applications of topology and
      two-dimensional NMR spectroscopy.
AB  - Unambiguous assignments of monocarboxymethylnapthalenes isolated as oxidation
      products of dimethylnaphthalenes by Pseudomonas putida, a bacterial strain, were
      made using two-dimensional nuclear Overhauser enhancement correlation
      spectroscopy (NOESEY). The two-dimensional long-range heteronuclear correlation
      NMR technique was also utilized for the assignment of quaternary carbons in the
      naphthalene system. In addition, we describe methods for prediction of 13C NMR
      chemical shifts of 2,6- and 2,7-disubstituted naphthalenes using topological
      approach. The method involves computation of molecular descriptors from
      topological representation of molecule, namely Wiener (W) and Szeged (Sz)
      indices. The results have shown that W and Sz indices can be successfully used
      for predicting 13C NMR chemical shifts and that Sigma13Cn can be used as a
      molecular property which in turn can be modeled by both W and Sz indices
      successfully.

PMID- 12217353
TI  - Structure-activity relationships of novel anti-malarial agents. Part 4: N-(3
      benzoyl-4-tolylacetylaminophenyl)-3-(5-aryl-2-furyl)acrylic acid amides.
AB  - In a previous report, we have described novel anti-malarial compounds based on a
      2,5-diaminobenzophenone scaffold. Here, we have invesigated acryloyl derivatives
      carrying a biaryl structure consisting of a terminal aryl residue and a central 2
      furyl ring. Several compounds were obtained in the series of para-substituted
      phenylfurylacryloyl derivatives that displayed improved anti-malarial activity in
      comparison to earlier described derivatives. From the structure-activity
      relationships it can be deduced that there has to be a lipophilic moiety in the
      para-position of the terminal phenyl residue. Furthermore, there are indications
      that, alternatively, activity may benefit from the presence of a polar moiety
      with hydrogen bond acceptor properties.

PMID- 12217354
TI  - Efficient liquid-phase synthesis of 2'-hydroxychalcones.
AB  - The condensation of 2'-hydroxyacetophenone (1) with aromatic aldehydes (2) in a
      well closed vessel using microwave irradiation or classical heating at 132
      degrees C, provides a fast and simple method for the liquid-phase synthesis of 2'
      hydroxychalcones without formation of by-products. Antiproliferative activity of
      these compounds were evaluated using MCF-7 cells.

PMID- 12217355
TI  - Analogue based design of MMP-13 (Collagenase-3) inhibitors.
AB  - 3D-QSAR studies using MFA and RSA methods were performed on a series of 39MMP-13
      inhibitors. Model developed by MFA method has a r(2)(cv) (cross-validated) of
      0.616 while its r(2) (conventional) value is 0.822. For the RSA model r(2)(cv)
      and r(2) are 0.681 and 0.847, respectively. Both the models indicate good
      internal as well as external predictive abilities. These models provide crucial
      information about the field descriptors for the design of potential inhibitors of
      MMP-13.

PMID- 12217356
TI  - Synthesis and evaluation of thymidine-5'-O-monophosphate analogues as inhibitors
      of Mycobacterium tuberculosis thymidylate kinase.
AB  - A number of 2'- and 3'-modified thymidine 5'-O-monophosphate analogues were
      synthesized as potential leads for new anti-mycobacterial drugs. Evaluation of
      their affinity for Mycobacterium tuberculosis thymidine monophosphate kinase
      showed that a 2'-halogeno substituent and a 3'-azido function are the most
      favorable leads for further development of potent inhibitors of this enzyme.

PMID- 12217357
TI  - Remarkable influence of the aromatic substructure in 9-methoxystrobilurin
      derivatives on their antifungal activity.
AB  - 9-Methoxystrobilurin-type beta-methoxyacrylate antibiotics (MOSBs) having various
      aromatic substructures were synthesized. The antifungal activity of the
      synthesized MOSBs against pathogenic and non-pathogenic fungi was examined, and
      the obtained results revealed that the antifungal activity of MOSBs was highly
      dependent on the aromatic substructures. However, no significant correlation was
      observed between cytotoxicity against human fibroblasts-like cell line and their
      structural properties. In addition, our results suggested that the strong growth
      inhibitory activity of 9-methoxystrobilurin K against human-derived cell lines
      should be related to its hindered ether-type substructure.

PMID- 12217358
TI  - Glutathione-like tripeptides as inhibitors of glutathionylspermidine synthetase.
      Part 2: substitution of the glycine part.
AB  - Glutathionylspermidine synthetase (GspS) is an essential enzyme in the
      biosynthesis of trypanothione and is an attractive target for the design of
      selective anti-parasitic drugs. We synthesised a series of analogues of
      glutathione (L-gamma-Glu-L-Leu-X) where the glycine moiety has been substituted
      for other amino acids. These peptides were evaluated as substrates and inhibitors
      of GspS. Compounds with basic side chains such as diaminopropionic acid were
      found to be good inhibitors (K(i): 7.2 microM). Substitution of the glycine part
      abolished the GspS substrate properties of the tripeptide.

PMID- 12217359
TI  - Synthesis and antiviral/antiproliferative activity of some N
      sulphonylbenzimidazoles.
AB  - Some benzimidazolyl sulphones were synthesized and evaluated for their antiviral
      and antiproliferative properties. Compound 10 displayed significant and selective
      activity against human cytomegalovirus (CMV), compound 14 showed activity against
      varicella zoster virus (VZV). The compounds were further evaluated for inhibitory
      effect on the proliferation of murine leukemia cells and human T-lymphocyte
      cells. Marked cytotoxicity was noted with different derivatives. Some structure
      activity relationships are discussed.

PMID- 12217360
TI  - Design and characterization of non-phosphopeptide inhibitors for Src family SH2
      domains.
AB  - The development of novel non-phosphopeptide inhibitors for the Src family SH2
      domain is described. Several commercially available hydroxyl aromatic acids have
      been appended off the N-terminus of pYEEIE and the potent phosphopeptide
      inhibitors of GST-Lck-SH2 were identified via ELISA. The most potent inhibitor,
      caffeic acid-pYEEIE, exhibited approximately 30-fold more binding activity than
      Ac-pYEEIE. Non-phosphopeptides were synthesized by replacing phosphotyrosine of
      caffeic acid-pYEEIE with tyrosine or 3,4-dihydroxyphenylalanine (DOPA). Caffeic
      acid-DOPA-EEIE that did not contain phosphotyrosine and its isosteres exhibited
      less than 20 times decreased binding affinity for GST-Lck-SH2 than Ac-pYEEIE.
      Moreover, it had a similar binding affinity for the GST-Lck-SH2, GST-Src-SH2, and
      GST-Fyn-SH2 domains. This study showed that the pY-1 positions of the
      phosphopeptide inhibitors and of the non-phosphopeptide inhibitors played an
      important role in the binding for the SH2 domain and that the non-phosphopeptide
      inhibitor must be a new lead in the development of SH2 inhibitors.

PMID- 12217361
TI  - 2,5-Pyridinedicarboxylic acid derivatives as non-nucleosidic reverse
      transcriptase inhibitors of hepatitis B virus.
AB  - 2,5-Pyridinedicarboxylic acid derivatives were found to be the potent non
      nucleoside inhibitors of hepatitis B virus (HBV) with IC(50) <or=0.01 microg/mL
      in a reverse transcriptase inhibitory effect. And they showed the low toxicity
      compared with the nucleoside analogues.

PMID- 12217362
TI  - Spirocyclic NK(1) antagonists II: [4.5]-spiroethers.
AB  - A series of novel spiroether-based neurokinin-1 (NK(1)) antagonists is described.
      The effect of modifications to the spiroether ring and aromatic substituents are
      discussed, leading to the identification of compounds with high affinity and
      excellent CNS penetration.

PMID- 12217363
TI  - Synthesis and mannose receptor-mediated uptake of clustered glycomimetics by
      human dendritic cells: effect of charge.
AB  - Effect of charge and shape of multivalent lysine-based cluster glycomimetics on
      their mannose receptor-mediated uptake by human dendritic cells has been
      evaluated: The capture is strongly affected by the shape of the ligands. The
      effect of charge is less pronounced although positive charges on the ligands seem
      to favor non-specific endocytosis capture.

PMID- 12217364
TI  - Synthesis and anticancer evaluation of vitamin K(3) analogues.
AB  - Novel vitamin K(3) analogues were synthesized and evaluated for their anticancer
      activity. Compound 6, 9, 10, 11, 14, and (+/-)15 demonstrated a strong inhibitory
      activity against the tumor cells of A-549, Hep G2, MCF7, MES-SA, MES-SA/Dx5,
      MKN45, SW-480, and TW-039. Compound (+/-)15 displayed potent tumor cell
      cytotoxicity, and compound 14 selectively affected MCF7, even though it did not
      influence normal cells Detroit551 and WI-38. Compound (+/-)15 inhibited MES-SA
      and MES-SA/Dx5, and this specific result shows that compound (+/-)15 may become a
      good anticancer drug candidate.

PMID- 12217365
TI  - Synthesis and evaluation of novel pyrrolidinyl sordaricin derivatives as
      antifungal agents.
AB  - N-Benzyl pyrrolidinyl sordaricin derivatives have been synthesized from cis-4
      hydroxy-D-proline in a stereocontrolled manner. These compounds maintained
      moderate antifungal activity against several pathogenic fungal strains. Their MIC
      values against Candida albicans were in the range of 0.25-2 microg/mL.

PMID- 12217366
TI  - Kinetic and mechanistic investigations on reductions of aflatoxins by lactic
      acid.
AB  - The kinetics of reduction of AFB(1) to AFB(2) and AFG(1) to AFG(2) by lactic acid
      has been investigated in dilute aqueous acidic solutions (pH 3.35-4.50) as a
      function of the concentrations of lactic acid, AFB(1), AFG(1) and hydrogen ion at
      37 degrees C. The rate of the reaction was found to be first order with respect
      to the concentrations of lactic acid and aflatoxins and independent on hydrogen
      ion concentration. The experimental results are interpreted in terms of
      mechanisms involving an initial formation of transient oxonium intermediate,
      which tends to polarize the olefinic (C=C) carbon, which in turn causes the
      hydride abstraction from alpha-carbon atom of lactic acid in rate determining
      step. The proposed mechanisms involve an overall transfer of two protons and two
      electrons from lactic acid to AFB(1) and AFG(1) to give the corresponding reduced
      less toxic products AFB(2) and AFG(2) and the oxidised product pyruvic acid.

PMID- 12217367
TI  - Electrostatic potential surfaces of 5-HT(3)R agonists suggest accessory cation-pi
      site adjacent to agonist binding domain.
AB  - Electrostatic potential surface mapping of various aromatic ring systems
      contained in 5-HT(3)R agonists indicate that some agonists contain an aromatic
      moiety capable of a favorable cation-pi interaction next to the e-face of
      pyridine (or its bioisostere). A pharmacophore model has been proposed based on
      superimposition of two distinct 'aryl' interactions.

PMID- 12217368
TI  - Synthesis of an arabinofuranosyl disaccharide photoaffinity probe for
      arabinosyltransferase activity in Mycobacterium tuberculosis.
AB  - (5-Azidonaphthalene-1-sulfonamidoethyl)-5-O-(alpha-arabinofuranosyl)-alpha-D
      arabinofuranoside 1 was synthesized as a photoaffinity probe for the
      determination of arabinosyl transferase activity and for the identification of
      binding and functional sites in Mycobacterium tuberculosis.

PMID- 12217369
TI  - Isomeric acetoxy analogues of rofecoxib: a novel class of highly potent and
      selective cyclooxygenase-2 inhibitors.
AB  - A group of isomers possessing a 2-, 3-, or 4-acetoxy moiety on the 3-phenyl
      substituent of rofecoxib were synthesized that exhibit highly potent, and
      selective, COX-2 inhibitory activity that have the potential to acetylate the COX
      2 isozyme.

PMID- 12217370
TI  - Sordarin oxazepine derivatives as potent antifungal agents.
AB  - The synthesis and biological activity of sordarin oxazepine derivatives are
      described. The key step features a regioselective oxidation of an unprotected
      triol followed by double reductive amination to afford the ring-closed products.
      The spectrum of antifungal activity for these novel derivatives includes coverage
      of Candida albicans, Candida glabrata, and Cryptococcus neoformans.

PMID- 12217371
TI  - 8-Anilinoimidazo[4,5-g]quinoline-7-carbonitriles as Src kinase inhibitors.
AB  - A series of 8-anilinoimidazo[4,5-g]quinoline-7-carbonitriles was synthesized and
      evaluated as Src kinase inhibitors. Several aniline substituents were surveyed,
      as well as water-solubilizing groups at the C-2 and N-3 positions. Potent Src
      inhibitors were identified, with N-3 providing the best position for an
      additional water-solubilizing group.

PMID- 12217372
TI  - Synthesis and initial SAR studies of 3,6-disubstituted pyrazolo[1,5
      a]pyrimidines: a new class of KDR kinase inhibitors.
AB  - We have synthesized and evaluated the activity of 3,6-disubstituted pyrazolo[1,5
      a]pyrimidines as a new class of KDR kinase inhibitors. Starting with screening
      lead 1, potency against isolated KDR was fully optimized with 3-thienyl and 4
      methoxyphenyl substituents at the 6- and 3-positions (3g, KDR IC(50)=19 nM),
      respectively. The synthesis and SAR of these compounds are described.

PMID- 12217373
TI  - Synthesis and activity of a novel class of tribasic macrocyclic antibiotics: the
      triamilides.
AB  - The stereoselective synthesis of two novel series of tribasic macrocyclic
      antibiotics with potent in vitro activity against Pasteurella multocida and
      Escherichia coli strains of bacteria is described. The in vitro activity can be
      significantly influenced by the nature of the substituents on the C-4"
      aminoalcohol, with the stereochemistry of the C-4" alcohol playing a less
      critical role. The effect of substitution and stereochemistry on the in vivo
      activity in a murine model of respiratory infection is also described.

PMID- 12217374
TI  - Synthesis of novel water soluble benzylazolium prodrugs of lipophilic azole
      antifungals.
AB  - Water soluble N-benzyltriazolium or N-benzylimidazolium salt type prodrugs of
      several highly lipophilic triazole or imidazole antifungals have been
      synthesized. They were designed to undergo an enzymatic activation followed by a
      self-cleavage to release a parent drug. The prodrugs such as 16 had enough
      chemical stability and water solubility for parenteral use and were rapidly and
      quantitatively converted to the active substance in human plasma.

PMID- 12217375
TI  - Development of a phosphatase-stable phosphotyrosyl mimetic suitably protected for
      the synthesis of high-affinity Grb2 SH2 domain-binding ligands.
AB  - Synthesis of (2R)-2-carboxymethyl-3-(4-(phosphonomethyl)phenyl) proprionic acid
      (5) in tert-butyl-protected form (6) and its use for the preparation of a Grb2
      SH2 domain-directed tripeptide (8a) is reported. In extracellular ELISA-based
      assays, 8a exhibits potent Grb2 SH2 domain binding affinity (IC(50)=8 nM).
      Against cultures of MDA-MB-453 breast cancer cells, which over-express erbB-2
      tyrosine kinase, 8a is also antimitogenic at concentrations equivalent to those
      required to inhibit intracellular association of Grb2 protein with phosphorylated
      p185(erbB-2) protein (IC(50)=8 microM). Analogue 6 may be useful for the
      preparation of a variety of phosphatase-stable SH2 domain-directed ligands.

PMID- 12217376
TI  - Multidrug resistant cancer cells susceptibility to cytotoxic taxane diterpenes
      from Taxus yunnanensis and Taxus chinensis.
AB  - Twelve taxane diterpenes (1-12), which were isolated previously from the EtOH
      extract of the aerial parts of Taxus yunnanensis or Taxus chinensis, were
      evaluated for cytotoxicity against the multidrug resistant cancer cells KB-VIN
      and KB-7d. Compounds and showed significant cytotoxicity in these cell lines.
      Compounds and also demonstrated significant activity against KB-7d. The
      biflavonoid isolated from T. yunnanensis was only marginally cytotoxic against
      the A549 (lung) cell line, but a simple methoxylated analogue (14) was inactive.

PMID- 12217378
TI  - Proceedings of the Fourth International Workshop on Signal Transduction in the
      Activation and Development of Mast Cells and Basophils. Bethesda, Maryland, USA.
      November 26-10, 2001.

PMID- 12217379
TI  - Effect of MITF on mast cell differentiation.
AB  - The mi transcription factor (MITF) is a basic helix-loop-helix leucine zipper
      (bHLH-Zip) transcription factor and encoded by the mi locus of mice. Double gene
      dose of mutant allele at the mi locus results the decrease of mast cells and
      phenotypic abnormalities of mast cells. Various mutations have been reported at
      the mi locus. We divided them to null and inhibitory mutations. The tg is a
      typical null mutation due to the insertion of a transgene into the promoter
      region of MITF gene. Adult mice of tg/tg genotype can easily obtained and are a
      potentially useful tool for studying development and function of mast cells.

PMID- 12217380
TI  - The function of MITF and associated proteins in mast cells.
AB  - Mutation of microphthalmia transcription factor (MITF) results in deafness, bone
      loss, small eyes, and poorly pigmented eyes and skin. The primary cell types
      affected in MITF-deficient mice are melanocytes, osteoclasts and mast cells. A
      search for MITF-associated proteins, using a mast cell library that was screened
      with a construct that encodes the basic helix-loop-helix leucine zipper (bHLH
      Zip) domain of MITF, resulted in the isolation of the protein kinase C
      interacting (PKCI) protein 1 and protein inhibitor of activated STAT3 (PIAS3). We
      have accumulated clear evidence of a function for these two proteins as
      repressors of MITF-induced transcriptional activity. Here, we describe this
      evidence and ideas that give some insight into the cellular network of
      interactions between various transcription factors and MITF.

PMID- 12217381
TI  - Activation of small GTPases of the Ras and Rho family by growth factors active on
      mast cells.
AB  - The small GTPases of the Ras and Rho families are activated by the key growth
      factors for mast cell development and survival, SLF and IL-3. While there are
      many clues that activation of Ras and Rho proteins play critical roles in growth,
      survival and differentiation, as well as in functions, such as migration and
      degranulation, limitations in the specificity of experimental tools still obscure
      their precise functions. There is increasing evidence that differences in
      subcellular localization of closely related GTPases determines important
      differences in their function. However, other data also point to differences in
      sensitivity to activation by GEF and in the effectors they engage.

PMID- 12217382
TI  - Stat5: an essential regulator of mast cell biology.
AB  - Interleukin-3 (IL-3) and stem cell factor (SCF) are important mast cell growth
      and differentiation factors. Since both cytokines activate the transcription
      factor Stat5, a known regulator of proliferation and survival, we investigated
      the effects of Stat5 deficiency on mast cell development and survival. This
      article will review data presented at The Fourth International Workshop on Signal
      Transduction in the Activation and Development of Mast Cells and Basophils. The
      full set of data is now in preparation for publication. We find that the absence
      of Stat5 A and B results in a total loss of in vivo mast cell development. Bone
      marrow-derived mast cell (BMMC) populations can be cultured and maintained from
      Stat5-deficient mice in IL-3+SCF, but not in either cytokine alone. The absence
      of Stat5 resulted in aberrant control of Bcl-2, Bcl-x(L) and cyclin A2, with
      increased apoptosis and delayed cell cycle progression after IL-3 or SCF
      stimulation. These results indicate that Stat5 A and B are critical regulators of
      in vitro and in vivo mast cell biology.

PMID- 12217383
TI  - Transcriptional regulation of the human high affinity IgE receptor alpha-chain
      gene.
AB  - Transcriptional regulation of the gene encoding human high affinity IgE receptor
      (Fc epsilon RI) alpha-chain was analyzed. Previously, we reported that GATA-1 and
      Elf-1 recognition sites were necessary for cell type-specific activation of the
      alpha-chain gene promoter. More detailed analysis revealed that other
      transcription factors bound the regions close to the Elf-1 recognition site and
      there was a more complex mechanism for the regulation of the promoter activity.
      On the other hand, during a course of studies to find cis-elements over this
      gene, CAGCTG sequence in the first intron was revealed to serve as an enhancer. A
      complex composed of USF1 and USF2 activated the human alpha-chain gene expression
      via this intronic element. Furthermore, we found two novel exons at 18.4 and
      12.6kb upstream from the reported first exon and discovered an additional distal
      promoter.

PMID- 12217384
TI  - SHIP represses mast cell activation and reveals that IgE alone triggers signaling
      pathways which enhance normal mast cell survival.
AB  - The hemopoietic specific, Src homology 2-containing inositol 5' phosphatase
      (SHIP) hydrolyzes the phosphatidylinositol (PI)-3-kinase generated second
      messenger, PI-3,4,5-trisphosphate (PIP(3)), to PI-3,4-bisphosphate (PI-3,4-P(2))
      in normal bone marrow derived mast cells (BMMCs). As a consequence, SHIP
      negatively regulates IgE+antigen (Ag)-induced degranulation as well as
      leukotriene and inflammatory cytokine production. Interestingly, in the absence
      of SHIP, BMMCs degranulate extensively with IgE alone, i.e. without Ag,
      suggesting that IgE alone is capable of stimulating signaling in normal BMMCs and
      that SHIP prevents this signaling from progressing to degranulation. To test
      this, we compared signaling events triggered by monomeric IgE versus IgE+Ag in
      normal BMMCs and found that multiple pathways are triggered by monomeric IgE
      alone and, while they are in general weaker than those stimulated by IgE+Ag, they
      are more prolonged. Moreover, while SHIP prevents this IgE-induced signalling
      from progressing to degranulation or leukotriene production it allows sufficient
      production of autocrine acting cytokines, in part by activation of NFkappaB, to
      enhance BMMC survival. Interestingly, the activation of NFkappaB and the level of
      cytokines produced are far higher with IgE than with IgE+Ag. Moreover, IgE alone
      maintains Bcl-X(L) levels and enhances the adhesion of BMMCs to fibronectin and
      this likely enhances their survival still further.

PMID- 12217385
TI  - Quantitative aspects of signal transduction by the receptor with high affinity
      for IgE.
AB  - Identification of the major components, how these interact with each other, and
      the modifications that follow in the sequence of events triggered by the receptor
      with high affinity for IgE, is progressing rapidly. A new challenge is to
      understand these interactions quantitatively. We present the fundamentals of the
      mechanistic model we are testing through mathematical modeling. The object is to
      see if the predictions of the model fit with the experimental results.

PMID- 12217386
TI  - Modeling the early signaling events mediated by FcepsilonRI.
AB  - We present a detailed mathematical model of the phosphorylation and
      dephosphorylation events that occur upon ligand-induced receptor aggregation, for
      a transfectant expressing FcepsilonRI, Lyn, Syk and endogenous phosphatases that
      dephosphorylate exposed phosphotyrosines on FcepsilonRI and Syk. Through model
      simulations we show how changing the ligand concentration, and consequently the
      concentration of receptor aggregates, can change the nature of a cellular
      response as well as its amplitude. We illustrate the value of the model in
      analyzing experimental data by using it to show that the intrinsic rate of
      dephosphorylation of the FcepsilonRI gamma immunoreceptor tyrosine-based
      activation motif (ITAM) in rat basophilic leukemia (RBL) cells is much faster
      than the observed rate, provided that all of the cytosolic Syk is available to
      receptors.

PMID- 12217387
TI  - A quantitative approach for studying IgE-FcepsilonRI aggregation.
AB  - Aggregation of cell surface receptors is a ubiquitous means of initiating signal
      transduction in many cellular systems. In this manuscript, we describe a combined
      theoretical and experimental approach based on multiparameter flow cytometry for
      measuring the time course of ligand induced aggregation of IgE-FcepsilonRI on RBL
      cells. By fluorescently labeling both the ligand and surface IgE (sIgE), we have
      developed an assay that permits us to simultaneously measure both occupancy of
      sIgE combining sites and association of antigen with the cell surface. This
      allows for a direct calculation of the degree of receptor aggregation present on
      the cell. By employing new mixing technologies developed for flow cytometry, we
      are able to look at aggregation in the sub second time domain. To extend our
      work, we have synthesized a new set of chemically well defined ligands (of
      valences 1-3) to use as probes in our studies. We show that the magnitude of the
      cellular response is dramatically increased as the valence of our ligand is
      raised from two to three.

PMID- 12217388
TI  - Protein tyrosine kinase Syk in mast cell signaling.
AB  - The tyrosine kinase Syk is essential for signaling from FcrepsilonRI in mast
      cells. The Src homology domain mediated binding of Syk to the phosphorylated
      immunoreceptor tyrosine-based motif (ITAM) of the receptor subunits results in a
      conformational change and activation. Studies in Syk deficient mast cells have
      defined the pathways that are activated upstream and downstream of Syk and have
      demonstrated the functional importance of the linker region of Syk in signaling
      in mast cells.

PMID- 12217389
TI  - Phospholipid scramblase, a new effector of FcepsilonRI signaling in mast cells.
AB  - The signaling network of the high-affinity receptor for IgE in mast cells
      involves tyrosine phosphorylation of a number of proteins. Here we report
      evidence that phospholipid scramblase, a protein involved in the distribution of
      phospholipids between the two leaflets of the plasma membrane, is a target for
      tyrosine kinases in this signal. The implication of this observation is briefly
      discussed.

PMID- 12217390
TI  - The roles of sphingosine-1-phosphate in asthma.
AB  - Asthma is a complex condition in which exposure to environmental antigens induces
      inflammatory reactions in the airway characterized by activation of mast cells
      and eosinophils. Mast cells are known to be the main effector cells in eliciting
      IgE-mediated allergic response. These cells secrete various substances that
      perpetuate inflammation and provoke airway smooth muscle (ASM) contraction. A
      newly recognized addition to the repertoire of FcepsilonRI-mediated signaling
      events is the activation of sphingosine kinase leading to the generation of the
      potent sphingolipid mediator, sphingosine-1-phosphate (S1P) from sphingosine. S1P
      secretion by the lung significantly increases after challenge with an allergen,
      adding this sphingolipid metabolite to the variety of mediators that are released
      during an allergic reaction [FASEB J. 15 (2001) 1212]. Indeed, similar to
      previous reports, we found that FcepsilonRI cross-linking not only increased
      cellular levels of S1P, it also markedly enhanced its secretion from rat
      basophilic leukemia RBL-2H3 cells. Moreover, S1P induced degranulation of RBL and
      bone marrow derived mast cells (BMMCs) cells as determined by hexosaminidase
      release. Treatment of BMMCs with the sphingosine kinase inhibitors, DL-threo
      dihydrosphingosine and dimethylsphingosine, reduced IgE/Ag stimulated histamine
      release. RT-PCR analysis demonstrated that these mast cells express S1P receptors
      EDG-1 and EDG-5 but not EDG-3, EDG-6 or EDG-8 transcripts. Further studies are
      needed to determine whether IgE triggering results in transactivation of EDG-1 or
      EDG-5 present on mast cells and whether this is a critical event for mast cell
      activation.

PMID- 12217391
TI  - Lipid rafts in mast cell signaling.
AB  - Lipid rafts are defined as plasma membrane microdomains enriched with
      glycosphingolipids and cholesterol which render them insoluble in non-ionic
      detergents. Many surface receptors are constitutively or inducibly associated
      with lipid rafts, and it has been suggested that the rafts function as platforms
      regulating the induction of signaling pathways. The signaling capacity of lipid
      rafts has been extensively studied in rat basophilic leukemia cells. An
      aggregation of lipid raft components, such as glycosylphosphatidylinositol (GPI)
      anchored glycoproteins (Thy-1 or TEC-21), triggers cell activation events which
      are similar to, but not identical with activation via the high-affinity IgE
      receptor (FcepsilonRI). Although FcepsilonRI in resting cells is not associated
      with lipid rafts, its aggregation induces a weak association with rafts and
      subsequent activation events. The properties of lipid rafts as well as the
      molecular mechanisms of their involvement in signal transduction are poorly
      understood. This review presents a critical analysis of recent results on
      structure-function relationship of lipid rafts and their regulatory role in
      signal transduction in mast cells.

PMID- 12217392
TI  - Macromolecular protein signaling complexes and mast cell responses: a view of the
      organization of IgE-dependent mast cell signaling.
AB  - The generation of signals following engagement of cell surface receptors is an
      ordered process that requires tight regulation as spurious signals could result
      in unwanted, and possibly deleterious, cellular responses. Like other cell
      surface receptors, stimulation of a mast cell via the high affinity IgE receptor
      (FcepsilonRI) causes multiple biochemical events that ultimately result in cell
      activation and effector responses. Recently, our knowledge of how these events
      are ordered has increased. We now have identified some of the molecules involved,
      how they are organized into macromolecular complexes by FcepsilonRI stimulation,
      and the role of some of the constituents of these macromolecular signaling
      complexes in mast cell effector responses. In brief, we review the knowledge on
      macromolecular signaling complexes used by FcepsilonRI in mast cell activation
      and provide our view on the regulation of signal generation and its effect on
      mast cell activation.

PMID- 12217393
TI  - FcepsilonRI signaling observed from the inside of the mast cell membrane.
AB  - Crosslinking the high affinity IgE receptor, FcrepsilonRI, on basophils and mast
      cells initiates cascades of biochemical events leading to degranulation, membrane
      ruffling and other physiological responses. Downstream of FcepsilonRI and its
      coupled tyrosine kinases, Lyn and Syk, scores of different proteins and lipids
      are implicated in these signaling cascades and new players are being identified
      continuously. Here, we use immunogold probes to label receptors and signaling
      proteins on the cytoplasmic face of membrane sheets prepared from RBL-2H3 mast
      cells and transmission electron microscopy to examine their distributions in
      relationship to each other and to features of the membrane. New topographical
      data are integrated with existing knowledge of the biochemistry of FcepsilonRI
      signaling and of cell shape during signaling to implicate at least two distinct
      membrane domains in FcepsilonRI signaling. "Primary signaling domains", also
      called osmiophilic patches, are recognized by their dark staining with osmium,
      adjacency to coated pits (previously mapped to planar membrane between lamellae)
      and by the characteristic presence of receptor, Syk and PLCgamma2, but not Lyn.
      "Secondary signaling domains" are characterized by the presence of large
      elliptical linker for activation of T cells (LAT) rafts and of PLCgamma1
      (previously mapped to lamellae) but not receptor. The signaling proteins, Vav,
      Grb2, Cbl and Gab2, and the endocytic proteins, AP2 and clathrin, all map to the
      primary domains, while the p85 regulatory subunit of phosphatidylinositol 3 (PI
      3)-kinase maps to both domains. Recognition that FcepsilonRI signaling is
      controlled not only by which chemical species are available for interaction, but
      also by where the interactions occur, may provide new opportunities for the
      modeling of signaling cascades and new targets for the development of drugs to
      treat allergies and asthma.

PMID- 12217394
TI  - Serine/threonine protein kinases synergistically regulate phospholipase D1 and 2
      and secretion in RBL-2H3 mast cells.
AB  - The role of phospholipase (PL) D in secretion was examined in RBL-2H3 mast cells
      which contain both PLD1 and 2. The effects of pharmacologic stimulants and
      inhibitors of Ca(2+)/calmodulin-dependent kinase II, protein kinase C, and
      protein kinase A suggested that all three kinases synergistically stimulate PLD
      and, when associated with a calcium signal, secretion as well to indicate a
      possible linkage between these two events. Overexpression of either PLD1 or 2
      markedly enhanced the activation of PLD by pharmacologic stimulants as well as
      antigen and both isoforms thus appear co-ordinately regulated. As the expressed
      PLD1 was associated with secretory granules and PLD2 with the plasma membrane,
      the two isoforms may serve distinct but complementary functions in secretion.

PMID- 12217395
TI  - Signalling role for ARF and phospholipase D in mast cell exocytosis stimulated by
      crosslinking of the high affinity FcepsilonR1 receptor.
AB  - Phospholipase D (PLD) catalyses the hydrolysis of phosphatidylcholine to generate
      the lipid second messenger, phosphatidate (PA). Two mammalian phospholipase Ds
      (PLD1 and PLD2) have been cloned and both are present in RBL-2H3 mast cells. PLD1
      is localised to secretory granules whilst PLD2 is localised to the plasma
      membrane, and the activity of both enzymes is increased upon antigen stimulation.
      Primary alcohols specifically interfere with the production of PLD-derived PA and
      are found to be potent inhibitors of antigen-stimulated exocytosis. One major
      intracellular regulator for PLD activity and exocytosis is ARF proteins, as
      depletion by permeabilisation leads to loss of both antigen-mediated PLD
      activation and exocytosis. Both responses can be restored in depleted cells by re
      addition of ARF1 or ARF6. ARF proteins and PLD-derived PA synergistically
      regulate the activity of a Type I PIP 5-kinasealpha. It is suggested that ARF, by
      activating PLD and PIP 5-kinase activities regulate PA and PI(4,5)P(2) levels,
      and both are critical components of the exocytosis machinery in mast cells.

PMID- 12217396
TI  - Cloning of rat Ras guanine nucleotide releasing protein 4, and evaluation of its
      expression in rat mast cells and their bone marrow progenitors.
AB  - We recently cloned a new mast cell (MC) restricted, Ras guanine nucleotide
      releasing protein (designated mRasGRP4) from IL-3-developed, mouse bone marrow
      derived MCs that can activate varied members of the Ras superfamily of small GTP
      binding proteins. We now describe the rat ortholog of this MC-specific guanine
      exchange factor. Using the mRasGRP4 gene and transcript in a homology-based
      cloning approach, the relevant transcript was isolated and sequenced from the
      spleen and lungs of Sprague-Dawley rats. Evidence for differential splicing of
      the rRasGRP4 transcript was obtained in the spleen. The rat basophilic leukemia 1
      MC line was found to express rRasGRP4, as well as the MC-committed progenitors
      residing in the bone marrow and the mature MCs residing in varied tissues of
      Sprague-Dawley rats. Based on its deduced amino acid sequence, rRasGRP4 is 93%
      identical to mRasGRP4. rRasGRP4 contains all of the functional domains present in
      the RasGRP family of guanine nucleotide exchange factors. Like its mouse
      ortholog, rRasGRP4 is a MC-restricted guanine exchange factor that contains
      Ca(2+) and phorbol ester/diacylglycerol-binding domains C-terminal of its CDC25
      like catalytic domain.

PMID- 12217397
TI  - Activation of human mast cells through the high affinity IgG receptor.
AB  - Mast cells are known to participate in the induction of inflammation through
      interaction of antigen with specific IgE bound to the high affinity receptor for
      IgE (FcepsilonRI). Human mast cells, derived from CD34(+) hematopoietic
      precursors, not only express FcepsilonRI but also express high affinity receptors
      for IgG (FcgammaRI), the latter only after IFN-gamma exposure. Human mast cells
      that express FcgammaRI are activated following FcgammaRI aggregation, either
      using antibodies directed to the receptor or through IgG bound to the receptor.
      This activation results in degranulation, with the release of granule-associated
      mediators, and the generation of metabolites of arachidonic acid and secretion of
      chemokines and cytokines. These observations provide evidence that human mast
      cells may also be recruited into inflammation through IgG-dependent mechanisms.

PMID- 12217398
TI  - Negative regulation of mast cell proliferation by FcgammaRIIB.
AB  - FcgammaRIIB are single-chain low-affinity receptors for the Fc portion of IgG
      antibodies that are widely expressed by hematopoietic cells including mast cells.
      We previously demonstrated that FcgammaRIIB negatively regulate cell activation
      triggered by receptors that possess Immunoreceptor Tyrosine-based Activation
      Motifs (ITAMs) including high-affinity IgE receptors (FcepsilonRI). FcgammaRIIB
      possess an Immunoreceptor Tyrosine-based Inhibition Motif (ITAM) whose deletion
      or mutation abolishes inhibition. When coaggregated with FcepsilonRI, the
      FcgammaRIIB ITIM is tyrosyl-phosphorylated by the src family protein tyrosine
      kinase lyn, and recruits the SH2 domain-containing inositol 5-phosphatase SHIP
      that accounts for inhibition of cell activation. We found recently that, when
      coaggregated with Kit, FcgammaRIIB can also inhibit mast cell proliferation:
      thymidine incorporation is inhibited, cells do not enter the G1 phase of the cell
      cycle, the induction of cyclins D2, D3 and A is inhibited, the activation of the
      MAP kinases Erk1/2, JNK and p38 is decreased, Akt phosphorylation is inhibited,
      and SHIP coprecipitates with FcgammaRIIB. Although inhibition of Akt
      phosphorylation and Erk activation was abrogated in SHIP(-/-) cells, inhibition
      of thymidine incorporation was only partially reduced. FcgammaRIIB-dependent
      inhibition of Kit-mediated mast cell proliferation was however mimicked by
      FcgammaRIIB whose intracytoplasmic domain was replaced by the catalytic domain of
      SHIP. We also found that FcgammaRIIB can inhibit the proliferation of cells whose
      proliferation was rendered growth factor-independent because they express a
      mutated form of Kit that renders this RTK constitutively activated. Based on
      these results we developed models aiming at using FcgammaRIIB as targets for new
      therapeutic approaches of disease associated with mast cell activation such as
      allergies and diseases associated with mast cell proliferation such as
      mastocytosis, mastocytomas or mast cell leukemias.

PMID- 12217399
TI  - Inhibition of anaphylactic inflammation by the gp49B1 receptor on mast cells.
AB  - gp49B1 is a member of the immunoglobulin (Ig) superfamily expressed on the
      surface of mast cells, macrophages, and activated natural killer cells. gp49B1
      inhibits FcepsilonRI-induced activation of mast cells in vitro by virtue of two
      immunoreceptor, tyrosine-based inhibitory motifs that recruit the SHP-1 tyrosine
      phosphatase to the plasma membrane. We created gp49B1 null mice by targeted gene
      disruption, and found that IgE-dependent mast cell activation is augmented in
      these animals. Moreover, the ensuing anaphylactic reactions and inflammation are
      enhanced in the absence of gp49B1. Thus, gp49B1 innately counter-regulates mast
      cell activation mediated by Ig generated through the adaptive immune response in
      vivo.

PMID- 12217400
TI  - An unusual inhibitory receptor--the mast cell function-associated antigen (MAFA).
AB  - The mast cell function-associated antigen (MAFA) is a type II membranal
      glycoprotein that was first identified on the surface of rat mucosal-type mast
      cells of the RBL-2H3 line. A C-type lectin domain and an immunoreceptor tyrosine
      based inhibitory motif (ITIM) are located in the extracellular and intracellular
      domains of MAFA, respectively. Human and mouse homologues of MAFA have been
      discovered recently. However, they are expressed also or only by NK and T-cells,
      where they most probably play different roles. MAFA clustering by its specific
      antibody mAb G63 has been previously shown to cause a dose-dependent inhibition
      of the secretory response of these cells to the FcepsilonRI stimulus. More recent
      results established that MAFA's inhibitory action involves at least two different
      enzymes: Following the tyrosyl-phosphorylation of MAFA ITIM by the PTK Lyn, two
      phosphatases SHIP and SHP2 are recruited to it at the plasma membrane where they
      propagate the inhibitory signals. The following is a brief report on this unusual
      inhibitory receptor and its functional activities.

PMID- 12217402
TI  - Association of the Src homology 2 domain-containing inositol 5' phosphatase
      (SHIP) to releasability in human basophils.
AB  - During the study of the biology of the Human recombinant Histamine Releasing
      Factor (HrHRF), we uncovered a hyperreleasable phenotype of basophils from HrHRF
      responder donors. Basophils from these donors released histamne to HrHRF, IL-3
      and D(2)O. While there has been a significant amount of work elucidating signal
      transduction events in human basophils, the reason for this hyperreleasable
      phenotype remained illusive. A clue to the releasability of these highly
      allergic, asthmatic HrHRF-responder donor basophils was demonstrated in studies
      using SHIP knockout mice. Bone marrow-derived mast cells from the SHIP knockout
      mice demonstrated hyperreleasability to stimuli through the IgE receptor and
      alteration of subsequent signal transduction events. We have demonstrated a
      highly significant negative correlation between the amount of SHIP protein per
      cell equivalent and maximum histamine release to HrHRF. These results provide a
      clue to the hyperreleasable phenotype and implicate SHIP as an additional
      regulator of secretion in human basophils.

PMID- 12217401
TI  - Interactions of the mast cell function-associated antigen with the type I
      Fcepsilon receptor.
AB  - Clustering the mast cell function-associated antigen (MAFA), a membrane
      glycoprotein expressed on 2H3 cells, by its specific monoclonal antibody G63
      substantially inhibits secretion normally triggered by aggregating these cells'
      Type I Fcepsilon receptor (FcepsilonRI). To explore possible MAFA-FcepsilonRI
      interactions giving rise to this inhibition, we have studied by time-resolved
      phosphorescence anisotropy the rotational behavior of both MAFA and FcepsilonRI
      as ligated by various reagents involved in FcepsilonRI-induced degranulation and
      MAFA-mediated inhibition thereof. From 4 to 37 degrees C the rotational
      correlation times (mean+/-S.D.) of FcepsilonRI-bound, erythrosin-conjugated IgE
      resemble those observed for MAFA-bound erythrosin-conjugated G63 Fab, 82+/-17
      micros and 79+/-31 micros at 4 degrees C, respectively. Clustering the
      FcepsilonRI-IgE complex by antigen or by anti-IgE increases the phosphorescence
      anisotropy of G63 Fab and slows its rotational relaxation. Lateral diffusion of
      G63 Fab is also slowed by antigen clustering of the receptor. Taken together,
      these results suggest that unperturbed MAFA associates with clustered
      FcepsilonRI. They are also consistent with its interaction with the isolated
      receptor, a situation also suggested by FRET measurements on the system.

PMID- 12217403
TI  - Regulation of ionomycin-mediated granule release from rat basophil leukemia
      cells.
AB  - Cross-linking the high affinity IgE receptor on the rat basophil leukemia clone
      2H3 (RBL-2H3) cell line, an vitro model for mast cell signaling, results in
      granule release. A great deal of research has focused on the earliest steps in
      this signaling cascade resulting in models which include the participation of
      lyn, syk, phospholipase C (PLC), protein kinase C (PKC) and intracellular calcium
      mobilization. In an effort to look at pathways downstream of calcium
      mobilization, ionomycin-mediated granule release was studied. The kinase
      inhibitors PP1 (src family), GF109203X (PKC), PD98059 (MEK1/2), and U0126
      (MEK1/2) substantially inhibited ionomycin-mediated granule release, while the
      p38 kinase inhibitor SB203580 did not. Both p38 and erk were phosphorylated upon
      ionomycin treatment, but only extracellular regulated kinase (erk) activation was
      completely inhibited by PP1 treatment and partially inhibited by the MEK
      inhibitors, thus, correlating with the granule release data. Interestingly, while
      GF109203X alone had no affect on erk activation, combining it with U0126
      completely blocked this response. This suggests the existence an alternate
      pathway for erk activation that is MEK independent and PKC dependent. Experiments
      in which ionomycin and PP1 were titrated (independently) demonstrated a
      correlation between erk phosphorylation and granule release, implicating erk in a
      PP1-inhibitable pathway operating downstream of calcium and controlling mast cell
      degranulation.

PMID- 12217404
TI  - Function of the t-SNARE SNAP-23 and secretory carrier membrane proteins (SCAMPs)
      in exocytosis in mast cells.
AB  - Mast cells acutely respond to allergens and other stimuli by releasing
      accumulated internal stores of inflammatory mediators and other secretory
      products by "compound" exocytosis involving massive granule-to-plasma membrane
      and granule-to-granule fusion. Our recent findings implicate the SNAP receptor
      (SNARE) protein SNAP-23 and secretory carrier membrane protein 2 (SCAMP2) as
      regulators of this process. We summarize evidence indicating that stimulus
      induced relocation of SNAP-23 from foci in the plasma membrane to putative sites
      of membrane fusion both at the cell surface and intracellularly between granules
      is an essential link in coupling stimulation to exocytosis. We also review recent
      findings showing that the candidate exocytotic SNAREs SNAP-23 and syntaxin 4
      colocalize with SCAMPs, especially SCAMP2, and that SCAMP2 is likely to be a
      partner in the compound exocytotic process.

PMID- 12217405
TI  - SNAREs and associated regulators in the control of exocytosis in the RBL-2H3 mast
      cell line.
AB  - Mast cells participate in inflammation and allergies by releasing biologically
      active mediators stored in numerous cytoplasmic granules. Degranulation is
      tightly controlled and requires activation of cell surface receptors, such as the
      high affinity IgE receptor (FcepsilonRI). Here, we discuss some of the key
      components of the molecular machinery that regulates the final steps of fusion
      between the granular and plasma membrane based on results obtained with the rat
      mast cell line RBL-2H3. We emphasize the role of soluble N-ethylmaleimide
      attachment protein receptors (SNAREs) proteins such as syntaxin 4 that can
      promote membrane fusion through formation of a stable complex with SNAP-23. We
      also highlight the role of a Ser/Thr kinase found to be associated with Rab3D, a
      negative regulator of degranulation. Associated kinase activity, which diminishes
      after stimulation as a consequence of intracellular calcium increases,
      specifically phosphorylates syntaxin 4 thereby affecting its capacity to bind to
      its t-SNARE partner SNAP-23. Our results suggest a new way of how Rab3 GTPases
      may intersect with the function of SNAREs thought to be universal mediators of
      membrane fusion.

PMID- 12217406
TI  - Synaptotagmin II negatively regulates MHC class II presentation by mast cells.
AB  - Synaptotagmins (Syts), comprise a gene family of proteins, implicated in the
      control of protein traffic. Rat basophilic leukemia cells (RBL-2H3), a tumor
      analogue of mucosal mast cells (MMC), express at least four distinct Syt
      homologues, including Syt II, Syt III, Syt V and Syt IX. Synaptotagmin II is
      located at the late/endosomal/lysosomal compartment, where it negatively
      regulates lysosomal exocytosis. Mast cells may contribute to immune defense
      mechanisms by presenting MHC class II/antigen complexes and triggering T cell
      dependent immune responses. We now demonstrate that RBL-2H3 mast cells, which
      express reduced levels of Syt II (<5%) by transfection with Syt II antisense
      cDNA, are able to release MHC class II molecules. We further show that release of
      both MHC class II molecules and of the lysosomal enzyme cathepsin D is stimulated
      by lipopolysaccharide (LPS, 1 microg/ml, 48h). We show further that LPS reduces
      by >40% the level of Syt II expression in both RBL-2H3 and bone marrow-derived
      mast cells (BMMC). This effect is both dose and time-dependent. These results
      indicate that Syt II can be down-regulated by external inflammatory signals,
      resulting in the amplification of mast cell function. Finally, our results
      implicate Syt II as an important and novel regulator of MHC class II
      presentation.

PMID- 12217407
TI  - New developments in the genetics and activation of mast cell proteases.
AB  - Mast cell chymases and tryptases exhibit an intriguing but potentially confusing
      variety of forms and functions. Thanks to recent genetic and biochemical
      advances, a clearer picture of phylogenetic and functional relationships in this
      large group of mammalian enzymes is emerging. Furthermore, there is increasing
      appreciation of the diversity of these enzymes among human populations. In
      humans, there appears to be just one mast cell chymase but multiple expressed
      tryptases, some of which are allelic variants and others of which are products of
      separate gene loci. New biological tools, including the dipeptidyl peptidase I
      (DPPI)-null mouse in which the entire class of mast cell chymases appears to be
      functionally knocked out, are helping to clarify the importance and specific
      roles of these most abundant of secreted mast cell proteins.

PMID- 12217408
TI  - Immunoregulatory properties of mast cell-derived exosomes.
AB  - Transmission of information from mast cells to neighboring or distant cells must
      be established continuously in order to ensure homeostasis or to initiate immune
      and inflammatory responses. Owing to their strategic location in peripheral
      tissues and their prompt response to various stimuli, mast cells can be
      considered as the cell prototype to fulfill such a sentinel function. There are
      several ways for mast cells to communicate with other cells including cell-cell
      interactions via membrane-associated receptors, cytokines and other soluble
      mediators, and a newly described messenger which consists of membrane vesicles
      called exosomes carrying a number of immunoregulatory molecules.

PMID- 12217409
TI  - Heterotypic adhesion-induced mast cell activation: biologic relevance in the
      inflammatory context.
AB  - In addition to being a major effector cell in the elicitation of allergic
      inflammation, mast cells have been found to be activated in various T cell
      mediated inflammatory processes and to reside in close physical proximity to T
      cells. Such observations have led investigators to propose a functional
      relationship between these two cell populations. In this regard, we have recently
      reported that murine and human mast cells can be activated to both release
      granule-associated mediators, such as histamine and matrix metalloproteinase-9
      (MMP-9), and to produce several cytokines (i.e. TNF-alpha, IL-4 and IL-6) upon
      physical contact, which is adhesion molecule mediated, with activated T cells.
      This cascade of events, whereby mast cells are activated by T cells to release
      certain mediators which are known to be essential for leukocyte extravasation and
      recruitment to affected sites, points to an important immunoregulatory function
      of mast cells within the context of T cell-mediated inflammatory processes.

PMID- 12217411
TI  - Mechanisms underlying mast cell influence on EAE disease course.
AB  - It is well established that CD4(+) T cells are of central importance in mediating
      the autoimmune destruction associated with the neurological demyelinating disease
      Multiple sclerosis (MS) and the rodent model of MS, EAE (experimental allergic
      encephalomyelitis). However, other cells also play a critical role in the
      inflammatory events that lead to the varying degrees of myelin and axonal damage
      observed in this disease syndrome. In this review, we present evidence that mast
      cells, best studied in the context of allergic disease, contribute to EAE disease
      pathology. Using mast cell-deficient mice, we demonstrate that mast cells are
      necessary for the full manifestation of MOG-induced EAE disease and show that
      cross-linking of Fc receptors is one mechanism of mast cell activation in
      disease. In addition, we provide evidence that mast cells exert influences
      outside the CNS, perhaps through the effects on the generation of the anti-MOG T
      cell response.

PMID- 12217410
TI  - Effects of eosinophils on mast cells: a new pathway for the perpetuation of
      allergic inflammation.
AB  - Mast cells have a clear-cut pathologic role in allergy, participating in a number
      of chronic inflammatory conditions, in helmintic parasitosis, and in some solid
      tumor reactions, but also in physiological situations, such as wound healing and
      innate immunity. Mast cells release a large number of proinflammatory,
      immunoregulatory, and tissue regulatory mediators after activation induced by
      either IgE-dependent or IgE-independent mechanisms. While much information has
      been gathered on the immunological mast cell activation both in rodent and human
      systems, only minimal knowledge exists on the non-immunological activation
      especially in human mast cells. Mast cell IgE-independent activation occurs
      through G(i3alpha) which has been identified as the pertussis toxin (Ptx)
      sensitive heterotrimeric G protein that interacts with cationic secretagogues
      inducing PLC-independent mast cell exocytosis. Mast cell IgE-independent
      activation in allergy probably occurs when mast cells encounter eosinophils, the
      main inflammatory cells of the allergic reactions that persist throughout the
      late phase and when the inflammatory condition becomes chronic. This review
      summarizes regarding the influence of eosinophils on mast cell activation, thus
      demonstrating that IgE-independent activation has a relevant role in
      pathophysiological processes as well as in mast cell IgE-dependent activation.

PMID- 12217412
TI  - Characterization of antimalarial SPf66 peptide using MALDI-TOF MS, CD and SEC.
AB  - SPf66 is the first chemically synthesized peptide to elicit a partial protective
      immune response against malaria. Size-exclusion chromatography (SEC) with multi
      angle laser light-scattering (MALLS) detection and hydrogen/deuterium (H/D)
      exchange monitored by (matrix-assisted laser desorption/ionization) MALDI-TOF
      (time-of-flight) mass spectrometry (MS) were used to assess the conformation and
      stability in aqueous solution after storage at different temperatures. Moreover,
      the feasible conformational changes of this peptide were also measured by
      circular dichroism (CD)-spectroscopy. The absolute molecular weight of SPf66
      monomer and dimer species were 4765 and 8960Da using SEC with MALLS detection,
      and 4643 and 9490Da by MALDI-TOF MS, the discrepancy being between both methods
      lower than 5.7%, a value quite close to those found in other proteins. The
      results from H/D exchange monitored by MALDI-TOF MS and CD-spectroscopy show that
      the SPf66 monomer lacks ordered structure, whereas the SPf66 dimer species
      presents segments of secondary structure as a determined by CD measurements.

PMID- 12217413
TI  - Significance of a carboxyl-terminal amide moiety in the folding and biological
      activity of crustacean hyperglycemic hormone.
AB  - Recombinant peptides related to Pej-SGP-I, one of several crustacean
      hyperglycemic hormones (CHHs) existing in the kuruma prawn Penaeus japonicus,
      were expressed in bacterial cells, and then purified after being allowed to
      refold. Their circular dichroism spectra suggested that the recombinant Pej-SGP-I
      having a free carboxyl-terminus (rPej-SGP-I-OH) differed slightly in secondary
      structure from the recombinant Pej-SGP-I having an amidated C-terminus (rPej-SGP
      I-amide). The hyperglycemic activity of rPej-SGP-I-amide was comparable to that
      of natural Pej-SGP-I, whereas rPej-SGP-I-OH showed weaker hyperglycemic activity
      by approximately one order of magnitude. These results indicate that the C
      terminal amide of CHH affects secondary structure and is significant in
      conferring hyperglycemic activity.

PMID- 12217414
TI  - Bradykinins and their precursor cDNAs from the skin of the fire-bellied toad
      (Bombina orientalis).
AB  - Bradykinin and (Thr(6))-bradykinin have been identified in the defensive skin
      secretion of the fire-bellied toad, Bombina orientalis. The homologous cDNAs for
      both peptides were cloned from a skin library using a 3'- and 5'-RACE strategy.
      Kininogen-1 (BOK-1) contained an open-reading frame of 167 amino acid residues
      encoding four repeats of bradykinin, and kininogen-2 (BOK-2) contained an open
      reading frame of 161 amino acid residues encoding two repeats of (Thr(6))
      bradykinin. Alignment of both precursor nucleotide and amino acid sequences
      revealed a high degree of structural similarity. These amphibian skin
      kininogens/preprobradykinins are not biologically analogous to mammalian
      kininogens.

PMID- 12217415
TI  - Antisense peptide nucleic acids conjugated to somatostatin analogs and targeted
      at the n-myc oncogene display enhanced cytotoxity to human neuroblastoma IMR32
      cells expressing somatostatin receptors.
AB  - Peptide nucleic acid (PNA) sequences are synthetic versions of naturally
      occurring oligonucleotides which display improved binding properties to DNA and
      RNA, but are still poorly internalized across cell membranes. In an effort to
      employ the rapid binding/internalization properties of somatostatin agonist
      analogs and the over-expression of somatostatin receptors on many types of tumor
      cells, PNAs complementary to target sites throughout 5'-UTR, translation start
      site and coding region of the n-myc oncogene were conjugated to a somatostatin
      analog (SSA) with retention of high somatostatin biological potency. IMR32 cells,
      which over-express somatostatin receptor type 2 (SSTR2) and contain the n-myc
      oncogene, were treated with these PNA-SSA conjugates. The results show that PNA
      conjugates targeted to the 5'-UTR terminus and to regions at or close to the
      translation start site could effectively inhibit n-myc gene expression and cell
      growth, whereas the non-conjugate PNAs were without effect at similar doses. The
      most potent inhibition of cell growth was achieved with PNAs binding to the
      translation start site, but those complementary to the middle coding region or
      middle upstream site between 5'-UTR and translation start site displayed no
      inhibition of gene expression. These observations were extended to four other
      cell lines: GH3 cells which express SSTRs with the n-myc gene, SKNSH cells
      containing a silent n-myc gene without SSTR2, HT-29 cells carrying the c-myc but
      no n-myc gene, and CHO-K1 cells lacking SSTR2 with n-myc gene. The results show
      that there was almost no effect on these four cell lines. Our study indicates
      that PNAs conjugated to SSA exhibited improved inhibition of gene expression
      possibly due to facilitated cellular uptake of the PNAs. These conjugates were
      mRNA sequence- and SSTR2-specific suggesting that many other genes associated
      with tumor growth could be targeted using this approach and that SSA could be a
      novel and effective transportation vector for the PNA antisense strategy.

PMID- 12217416
TI  - Isolation of cathepsin B inhibitory peptides, Cabin-A1 and -A2, from a tryptic
      and chymotryptic hydrolysate of human serum albumin.
AB  - Two novel peptides that inhibit cathepsin B were isolated from a tryptic and
      chymotryptic hydrolysate of human serum albumin, and designated as Cabin-A1 and 
      A2. Cabin-A1 and -A2 were purified by reversed-phase HPLC and identified as Ser
      Leu-His-Thr-Leu-Phe and Phe-Gln-Asn-Ala-Leu, respectively. These peptides
      correspond to f(65-70) and f(403-407) of human serum albumin. Human albutensin A
      (Ala-Phe-Lys-Ala-Trp-Ala-Val-Ala-Arg), which corresponds to f(210-218), was also
      isolated as a potent cathepsin B inhibitor. Synthetic Cabin-A1, -A2, and human
      albutensin A showed dose-dependent inhibition of cathepsin B, with K(i) values of
      2.4, 290, and 3.8 microM, respectively.

PMID- 12217417
TI  - In vitro quantitative study of the degradation of endomorphins.
AB  - The catabolism of the endomorphins was investigated in detail. The endomorphins
      were degraded relatively slowly in the rat brain homogenate (t1/2(endomorphin
      1)=4.94 min; t1/2(endomorphin-2)=3.81 min). The inhibition of metalloproteases
      and aminopeptidases stabilised the endomorphins to the greatest extent. The
      digestion of endomorphins tritiated specifically on Tyr(1), Pro(2) or Phe(3)
      established also that only the aminopeptidase pathways were essential for
      inactivation of the endomorphins, and that the tetrapeptides were degraded by
      cleavage of the Pro(2)-Trp(3) or Pro(2)-Phe(3) bond. The end-products of the
      catabolism were amino acids; the fragments Tyr-Pro-OH and Pro-Trp-Phe-NH2 were
      present as intermediates. Metabolites produced by brain carboxypeptidases were
      not detected.

PMID- 12217418
TI  - Does nociceptin play a role in pain disorders in man?
AB  - Nociceptin-immunoreactive cellbodies were detected in the human trigeminal
      ganglion, while no such fibers were identified in the temporal artery or in
      dermal tissue from the neck region. In four healthy subjects receiving nociceptin
      into the temporal muscle in an open labeled design no pain was detected. In 10
      healthy subjects who received 200pmol of nociceptin into tender non-dominant
      trapezius muscles in a placebo-controlled, randomized, balanced, and double
      blinded design local tenderness increased (P=0.025) while no pain was noted.
      Thus, the action of nociceptin should be searched for in the trigeminal ganglion
      and/or in the central nervous system (CNS).

PMID- 12217419
TI  - Lack of the nociceptin receptor does not affect acute or chronic nociception in
      mice.
AB  - The peptide nociceptin/orphanin FQ (N/OFQ) and its receptor ORL-1, also
      designated opioid receptor 4 (OP(4)) are involved in the modulation of
      nociception. Using OP(4)-knockout mice, we have studied their response following
      opioid receptor stimulation and under neuropathic conditions.In vas deferens from
      wild-type and OP(4)-knockout mice, DAMGO (mu/OP(3) agonist), deltorphine II
      (delta/OP(1) agonist) and (-)-U-50488 (kappa/OP(2) agonist) induced similar
      concentration-dependent inhibition of electrically-evoked contractions. Naloxone
      and naltrindole (delta/OP(1) antagonists) shifted the curves of DAMGO (pA(2)=8.6)
      and deltorphine II (pA(2)=10.2) to the right, in each group. In the hot-plate
      assay, N/OFQ (10 nmol per mouse, i.t.) increased baseline latencies two-fold in
      wild-type mice while morphine (10mg/kg, s.c.), deltorphine II (10 nmol per mouse,
      i.c.v.) and dynorphin A (20 nmol per mouse, i.c.v.) increased hot-plate latencies
      by about four- to five-fold with no difference observed between wild-type and
      knockout mice. Furthermore, no change was evident in the development of the
      neuropathic condition due to chronic constriction injury (CCI) of the sciatic
      nerve, after both thermal and mechanical stimulation. Altogether these results
      suggest that the presence of OP(4) receptor is not crucial for (1) the
      development of either acute or neuropathic nociceptive responses, and for (2) the
      regulation of full receptor-mediated responses to opioid agonists, even though
      compensatory mechanisms could not be excluded.

PMID- 12217420
TI  - Different effects of methionine-enkephalin on paw edema in two inbred rat
      strains.
AB  - The effect of intraplantarly (i.pl.)-injected methionine-enkephalin (ME) on
      Concanavalin A (Con A)-induced paw edema in Dark Agouti (DA) and Albino Oxford
      (AO) rats was investigated. ME suppressed edema in DA rats, which was antagonized
      with naloxone (non-selective opioid receptor antagonist) and naltrindole (delta
      opioid receptors antagonist). Potentiating effect of ME in AO rats was blocked by
      naloxone, nor-binaltorphimine (kappa opioid receptors antagonist) and beta
      funaltrexamine (mu opioid receptors antagonist). Dexamethasone suppressed edema
      in both rat strains. These findings suggest that strain-dependent differences in
      the effects of ME on inflammation in DA and AO rats could be related to diversity
      in opioid receptors expression in these strains.

PMID- 12217421
TI  - Cloning and characterization of murine neuromedin U receptors.
AB  - Neuromedin U (NmU) is a neuropeptide involved in various physiological functions
      such as feeding behavior, muscle contractile activity, and regulation of
      intestinal ion transport. Recently, two human G protein-coupled receptors have
      been identified as NmU-specific receptors, NmU-R1 and NmU-R2, which share 55%
      amino acid identity. It is unclear however, which of the two receptors mediates
      responses to NmU observed in rodent models. Attempts to define the
      pharmacological profile of the two receptors are confounded by overlapping
      expression of the two receptors and a lack of subtype-selective compounds. In
      order to establish a basis to further our understanding of the function of these
      receptors, we cloned and characterized the mouse homologues of the two human NmU
      receptors. Mouse NmU-R1 and mouse NmU-R2 are 79 and 81% identical to their
      respective human homologues. Expression of NmU-R1 was mainly observed in testis,
      gastrointestinal (GI) tract, and immune system, while NmU-R2 was primarily
      expressed in brain tissues. Each mouse receptor was independently expressed in
      HEK293 cells and demonstrated a dose-dependent calcium flux in response to NmU-8,
      NmU-23 and NmU-25. In an attempt to identify a synthetic NmU peptide that would
      exhibit selectivity at one of the two receptors, we examined the functional
      activity of eight alanine-substituted NmU-8 peptides. These experiments
      demonstrated that alanine substitution at positions 5 and 7 affects the
      functional activity of the peptide at both receptors. The arginine residue at
      position 7 is required for NmU-8 activity at either receptor while alanine
      substitution at position 5 selectively affects the potency and the efficacy at
      mNmU-R1. These experiments validate the use of rodent models to characterize NmU
      function relative to humans and suggest that substitution at Arginine-5 of NmU-8
      may provide a receptor selective peptide.

PMID- 12217422
TI  - Developmental pattern of tachykinins during aging in several organs: effect of
      exogenous melatonin.
AB  - Mammalian neurokinin A (NKA) and substance P (SP) are neuropeptides widely
      distributed in the body; they are potential regulators of the basal blood flow
      and therefore of the function of many organs and tissues. In the present
      investigation, we studied the age-dependent changes in NKA and SP in ovary,
      liver, pancreas and spleen as well as the role of exogenous melatonin on these
      changes. Female rats of 5, 15 or 25 months of age were studied. In the ovary, NKA
      concentrations did not change during aging. SP concentrations in the control
      group were significantly higher (P<0.01) in old rats than in the other two age
      groups studied. Melatonin treatment resulted in reduced concentrations as
      compared with those of the control old rats. In the pancreas, NKA and SP
      concentrations increased during aging, the young rats showing significantly lower
      values (P<0.01) than middle-aged and old rats for NKA and significantly lower
      (P<0.01) than the old rats for SP. After melatonin treatment the differences in
      NKA concentrations disappeared and SP decreased in middle-aged as compared with
      those in old rats. In the liver, NKA and SP concentrations in the control and
      melatonin-treated groups did not differ significantly for the three age groups
      studied. Splenic NKA in control and melatonin-treated groups increased from young
      to middle-age up to old ages. SP concentrations showed similar values at all ages
      except in melatonin-treated old rats; in these animals there were significantly
      higher concentrations than in young melatonin-treated rats. The effect of
      melatonin was mainly observed on the ovary and pancreas in old rats, with a
      reduction in the concentrations as compared with those observed in the young
      groups.

PMID- 12217423
TI  - The effects of acute and chronic alpha melanocyte stimulating hormone (alphaMSH)
      on cardiovascular dynamics in conscious rats.
AB  - Alpha melanocyte stimulating hormone (alphaMSH) has been demonstrated to have
      regulatory functions in the periphery and central nervous system (CNS). alphaMSH
      plays a central role in the regulation of metabolic balance such as decreasing
      food intake, increasing sympathetic outflow and hypothalamic/pituitary function.
      Our laboratory has investigated the actions of alphaMSH on sympathetic and
      cardiovascular dynamics using anesthetized animals. In this study we determined
      both the acute and chronic effects of alphaMSH on cardiovascular and metabolic
      dynamics in conscious unrestrained rats. Animals were each implanted with a radio
      telemetry transmitter for recording of cardiovascular parameters and subsequently
      instrumented with intracerebroventricular (ICV) cannulas. The acute ICV
      administration of alphaMSH significantly increased the mean arterial pressure
      (MAP) and heart rate (HR) when compared to artificial cerebrospinal fluid (ACSF)
      controls. On the other hand chronic alphaMSH infusion resulted in an initial
      increase in MAP and HR lasting for 2 days followed by a decrease in MAP. Chronic
      alphaMSH administration decreased physical activity and food intake but not
      weight gain. We conclude that in the conscious unrestrained animal the acute
      administration of alphaMSH increased MAP and HR, however, chronic infusion is
      associated with decreased MAP, physical activity and food intake.

PMID- 12217424
TI  - Cardiovascular effects of urotensin II in different brain areas.
AB  - It has been shown that intracerebroventricular injection of urotensin II (UII)
      induced hypotensive and bradycardiac responses. Here, we tested the
      cardiovascular roles of UII in different brain areas by microinjection of UII
      into the A1 and A2 areas (noradrenergic cells found in the lower part of the
      medulla that have been designated either A1 or A2 areas), the paraventricular and
      the arcuate nucleus. In urethane-anaesthetized rats, we observed that: (1)
      microinjection of UII into the A1 area induced dose-related depressor and
      bradycardiac responses; (2) mean arterial blood pressure (mABP) and heart rate
      (HR) did not change significantly after microinjection of UII into the A2 area;
      and (3) significant increases in mABP and HR were induced after microinjection of
      10 pmol UII into either the paraventricular or arcuate nucleus. The above results
      suggest that UII, in different brain areas, plays different roles in
      cardiovascular regulation and the A1 area is a very important action site for UII
      in cardiovascular regulation.

PMID- 12217425
TI  - A-type natriuretic peptide receptor in the spontaneously hypertensive rat kidney.
AB  - Renal NPR-A binding characteristics was examined in SHR. Renal ANP binding sites
      of NPR-A showed a lower maximal binding capacity and higher affinity in SHR than
      in WKY at all intrarenal sites. Despite the lower B(max) in SHR, both ANP(1-28)
      and ANP(5-25) stimulate similar or greater cGMP production in isolated glomeruli.
      Studies on guanylate cyclase from glomerular and papillary membranes have
      reported an increased basal and stimulated guanylate cyclase activity in SHR. The
      present study provides further evidences for altered NPR-A receptors in SHR
      kidney, which might act as a negative feedback in response to hypertension.

PMID- 12217426
TI  - GRP mediates an inhibitory response of gut-related vagal motor neurons to PVN
      stimulation.
AB  - We previously characterized neurons in the dorsal motor nucleus of the vagus
      (DMNV) that were modulated by electrical stimulation of the PVN and by
      gastrointestinal distention. Bombesin has been identified in a subset of PVN
      neurons projecting to the DMNV. It is currently unknown whether this
      neurotransmitter is involved in descending communication from PVN to DMNV
      neurons. In this study we determined whether the specific bombesin antagonist, N
      acetyl-GRP(20-26), influenced (1) the basal firing rate of DMNV neurons and (2)
      the response to electrical current stimulation of the PVN. Our results indicate
      that N-acetyl-GRP(20-26), significantly attenuated the inhibitory response of
      DMNV neurons to PVN stimulation. These results provide a possible mechanism by
      which bombesin regulates gastrointestinal function, body temperature homeostasis,
      and feeding behaviors.

PMID- 12217427
TI  - alpha2-Adrenoceptors control the release of noradrenaline but not neuropeptide Y
      from perivascular nerve terminals.
AB  - Neuropeptide Y (NPY) and noradrenaline (NA) are co-transmitters at many
      sympathetic synapses, but it is not yet clear if their release is independently
      regulated. To address this question, we quantified the electrically evoked
      release of these co-transmitters from perivascular nerve terminals to the
      mesenteric circulation in control and drug-treated rats. 6-Hydroxydopamine
      reduced the tissue content and the electrically evoked release of ir-NPY and NA
      as well as the rise in perfusion pressure. A 0.001 mg/kg reserpine reduced the
      content of ir-NPY and NA, but did not modify their release nor altered the rise
      in perfusion pressure elicited by the electrical stimuli. However, 0.1mg/kg
      reserpine reduced both the content and release of NA but decreased only the
      content but not the release of ir-NPY; the rise in perfusion pressure was halved.
      Clonidine did not affect the release of ir-NPY while it lowered the outflow of
      NA, not altering the rise in perfusion pressure elicited by the electrical
      stimuli. Yohimbine, did not modify the release of ir-NPY but increased the NA
      outflow, it antagonized the clonidine effect. Therefore, presynaptic alpha2
      adrenoceptors modulate the release of NA but not NPY, implying separate
      regulatory mechanisms.

PMID- 12217428
TI  - Arousal effects of orexin-A correlate with GLU release from the locus coeruleus
      in rats.
AB  - Although orexin was found to promote food intake, recent reports proposed its
      involvement in the regulation of vigilance. To study the mechanism of how orexin
      affects arousal, we analyzed glutamate (GLU) release from the locus coeruleus
      (LC) in rats after systemic injection of orexin-A. Baseline levels of orexin-A in
      the LC were significantly higher during the dark period than the light period.
      Intravenous administration of orexin-A increased GLU levels as well as orexin in
      the LC, simultaneously promoting wakefulness. These results suggest that
      increases in GLU release may reflect the arousal-inducing effects of orexin.

PMID- 12217429
TI  - Effects of orexin-A on memory processing.
AB  - Orexin-A is an endogenous peptide with receptors present throughout the brain.
      Here, we examined the effect of post-training administration of orexin-A on
      retention in active and passive avoidance. Orexin-A administered by
      intracerebroventricular (i.c.v.) injection to CD-1 mice post-training improved
      retention in both T-maze footshock avoidance and one trial step-down passive
      avoidance. SAMP8 mice have age-related deficits in learning and memory, which
      correlate with an increase in brain levels of beta amyloid (Abeta) and an
      impaired response to memory-enhancing compounds. Orexin-A at 3nmol improved
      retention in young and old SAMP8 mice. These findings show that orexin-A can
      improve memory even with overproduction of Abeta.

PMID- 12217430
TI  - Expressions of the prepro-orexin and orexin type 2 receptor genes in obese rat.
AB  - We examined the expressions of the prepro-orexin gene in the lateral hypothalamic
      area (LHA), the genes of the neuropeptide Y (NPY) and proopiomelanocortin (POMC)
      in the arcuate nucleus (ARC), the orexin type 1 receptor (OX1R) gene in the
      ventromedial hypothalamic nucleus (VMH) and the orexin type 2 receptor (OX2R)
      gene in the paraventricular nucleus (PVN) in 6-, 12- and 18-week-old male lean
      (Fa/?) and obese (fa/fa) Zucker rats, using in situ hybridization histochemistry.
      The fa/fa rats showed hyperglycemia at 12- and 18-week-old. The prepro-orexin
      mRNA level in fa/fa rats at 18-week-old and the OX2R mRNA level in fa/fa rats at
      12- and 18-week-old were significantly decreased compared to controls. The NPY
      mRNA levels in fa/fa rats at each time point were significantly increased
      compared to controls, but the POMC mRNA levels were decreased. Prepro-orexin and
      OX2R mRNA levels in fa/fa rats pretreated with insulin normalized to the levels
      found in Fa/? rats. These results suggest that the regulation of prepro-orexin
      gene expression might be independent of the regulation of the NPY and POMC genes
      in the ARC in fa/fa rats.

PMID- 12217431
TI  - Estradiol treatment fails to affect the feeding responses to melanocortin-3/4
      receptor agonism or antagonism in ovariectomized rats.
AB  - The involvement of the hypothalamic melanocortin-3 and -4 (MC3/4) receptors
      system in the inhibitory actions of estradiol (E2) on feeding was investigated.
      Ovariectomized Long-Evans rats with lateral ventricular (LICV) injection cannulae
      were maintained on a near-physiological, cyclic schedule of E2 treatment. LICV
      injections of 0.5 nmol of the MC3/4 agonist MTII decreased feeding, and LICV
      injections of the MC3/4 antagonists SHU9119 (12.5-500 pmol) and AgRP (1.0 nmol)
      stimulated feeding. None of these effects was affected by E2 treatment. Thus,
      hypothalamic MC3/4 receptors play a physiological role in the control of feeding
      in female rats as in males but do not mediate E2's feeding effects during the
      ovarian cycle.

PMID- 12217432
TI  - Peptides acting at gap junctions.
AB  - Gap junction channels are low resistance pathways allowing an action potential to
      propagate from one cell to the neighboring. Moreover, small molecules (<1000 Da)
      may pass the channel providing a possibility for metabolic coupling, growth and
      differentiation control of a cell by its surrounding. Antiarrhythmic peptides can
      enhance the conductivity of the channels while other peptides, angiotensin or
      extracellular loop peptides, reduce intercellular communication. On the other
      hand, peptides like angiotensin II or endothelin-1 can increase expression of
      certain gap junction channel proteins and, thereby, may affect intercellular
      coupling chronically. Thus, intercellular communication can be controlled using
      peptide drugs.

PMID- 12217433
TI  - Ultrasonic measurement of bladder weight as a possible predictor of acute urinary
      retention in men with lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia.
AB  - Acute urinary retention (AUR) is one of the most undesirable events for elderly
      men with benign prostatic hyperplasia (BPH). This study was designed to test the
      clinical utility of ultrasonic measurement of bladder weight as a predictor of
      AUR. A total number of 160 men visited our clinic with lower urinary tract
      symptoms (LUTS) suggestive of BPH and underwent urodynamic studies, including
      transrectal ultrasonography of the prostate and the measurement of ultrasound
      (US) estimated bladder weight (UEBW). Among them, 31 (19.4%) presented to our
      clinic with AUR. From the thickness of the anterior bladder wall measured by
      transabdominal ultrasonography and the intravesical volume, UEBW was calculated,
      supposing the bladder to be a sphere. Between patients with and without AUR,
      there were significant differences for age (75.4 vs. 71.1 years, p < 0.005),
      prostatic volume (45.5 vs. 35.8 g, p < 0.05), transition zone (TZ) volume (29.4
      vs. 20.2 g, p < 0.05), TZ index (0.606 vs. 0.493, p < 0.005) and UEBW (50.3 vs.
      34.7 g, p < 0.0001). A receiver-operating characteristic curve analysis
      demonstrated UEBW to be superior to the other prostatic ultrasonic measures in
      identifying AUR. Patients with LUTS suggestive of BPH having UEBW greater than
      35.0 g were 13.4 times as likely to suffer from AUR. The significant association
      of UEBW with an increased risk of AUR suggests that it would be promising as a
      noninvasive urodynamic parameter capable of identifying patients at increased
      risk of AUR.

PMID- 12217434
TI  - Ultrasound estimation of fetal weight with the use of computerized artificial
      neural network model.
AB  - The aim of this study was to test if the computerized artificial neural network
      (ANN) model could improve ultrasound (US) estimation of fetal weight over
      estimation with the other commonly used formulas generated from regression
      analysis. First, as the training group, we performed US examinations on 991
      singleton fetuses within 3 days of delivery. Six input variables were used to
      construct the ANN model: biparietal diameter (BPD), occipitofrontal diameter
      (OFD), abdominal circumference (AC), femur length (FL), gestational age and fetal
      presentation. Second, a total of 362 fetuses were assessed subsequently as the
      validation group. In this training group, the ANN model was better than the other
      compared formulas in fetal weight estimation (n = 991, mean absolute error 183.83
      g, mean absolute percent error 6.02%, all p < 0.0001). In addition, the
      validation group further proved the results (n = 362, mean absolute error 179.91
      g, mean absolute percent error 6.15%, all p < 0.005). In conclusion, the
      computerized artificial neural network (ANN) model could provide better US
      estimation of fetal weight than estimations by means of commonly used formulas
      generated from regression analysis.

PMID- 12217435
TI  - Intracardiac and intraluminal echocardiography: indications and standard
      approaches.
AB  - In particular clinical scenarios, transthoracic and transoesophageal
      echocardiography (TEE) have limitations. This study sought to test if
      intracardiac and intraluminal echocardiography (ICLE), including 2-D, M-mode and
      Doppler analysis with a miniaturised, multiple-frequency transducer-tipped
      catheter, is suitable for assessing distinct cardiac and vascular disorders. ICLE
      was employed in 10 animals using 6 standard approaches. In 12 patients undergoing
      device closure of patent foramina ovalia (PFO) (n = 6) or atrial septal defects
      (ASD) (n = 3), or aortic stent implantation (n = 3), interventional procedures
      were guided by ICLE and, for comparison, also by TEE. ICLE provided enhanced
      diagnostic information on the aorta, cardiac valves, main pulmonary vessels and
      both atria and, therefore, added to the diagnostic spectrum of TEE. Especially
      for guiding interventional procedures (e.g., device closure of atrial septal
      defects and patent foramina ovalia), ICLE was shown to be helpful. Compared with
      the conventional approach, the technique reduced fluoroscopy time for device
      closure procedures: 6.5 min vs. 8.9 min, p < 0.0011. With the patient in a supine
      position, ICLE was better tolerated than TEE. Complications did not occur, either
      with ICLE or with TEE. In conclusion, ICLE adds to conventional echocardiography
      and promises to become a clinical alternative for guiding interventional
      procedures.

PMID- 12217436
TI  - Effects of Optison on pulmonary gas exchange and hemodynamics.
AB  - Optison is a contrast-enhancing agent used in myocardial contrast
      echocardiography. It consists of small albumin spherules (approximately 4-microm
      diameter) containing a fluorocarbon gas, octafluoropropane. It is injected IV
      and, thus, may cause pulmonary manifestations of microembolism. To determine if
      any such effects do occur, we injected sequential doses of 1, then 3 and then 5
      mL Optison IV into 25 kg anesthetized dogs, and measured pulmonary hemodynamic
      and gas exchange variables frequently for 30 min after each dose. This was done
      in both 6 healthy and 6 pulmonary hypertensive animals, the latter produced by
      acute IV injection of 676-microm diameter polystyrene beads, raising pulmonary
      artery pressure from normal (15 mmHg) to 33 mmHg. Optison-injected animals were
      compared with albumin-injected controls. Two animals developed severe hypotension
      in response to albumin and could not be used. Lung compliance and wet/dry weight
      ratio were unaffected by Optison and no effects on gas exchange were seen at any
      dose or time in either group of dogs. In the healthy group, there was slight (1
      mmHg per mL Optison, transient and delayed pulmonary hypertension without change
      in cardiac output, suggesting a vasoconstrictor rather than mechanical basis for
      these small effects. No such changes occurred in the pulmonary hypertensive
      group. These results imply that usual human doses of Optison (0.5 mL) will
      produce no significant hemodynamic or gas exchange effects in either healthy or
      pulmonary hypertensive dogs.

PMID- 12217437
TI  - Brachial artery shear stress is independent of gender or age and does not modify
      vessel wall mechanical properties.
AB  - The objective of the present study was to obtain brachial artery (BA) baseline
      shear stress (SS) values in healthy volunteers and to relate this to gender and
      age. Peak and mean wall shear rate (SR) were noninvasively measured in 30 healthy
      subjects using an SR estimation system. Arterial diameter and wall
      characteristics were obtained with a wall tracking system. SS was estimated from
      SR and calculated whole blood viscosity. Intrasubject variability and the effects
      of age and gender were assessed. Intrasubject variability of BA peak and mean SR
      were 16.2% and 28.6%. Baseline peak ( approximately 3.0 +/- 0.7 Pa) and mean SS (
      approximately 0.5 +/- 0.2 Pa) were not gender-dependent, nor were they influenced
      by age. No vessel wall parameter related to BA SS. No differences in BA SS were
      observed between the genders and no influence of age was apparent. Our results
      indicate that the BA adequately responds to chronic changes in blood flow.

PMID- 12217438
TI  - Estimation of choroid perfusion by colour Doppler imaging vs. other methods.
AB  - Ocular haemodynamics play a prominent role in several ocular diseases. Recently,
      new methods for the determination of ocular perfusion were developed. Colour
      Doppler imaging (CDI) of orbital vessels has come up in the past decade and was
      shown to be useful in ophthalmological diagnostics. Little is known about
      measurement of choroid perfusion by CDI in comparison with other methods.
      Therefore, 49 eyes were examined with CDI, laser Doppler flowmetry (LDF) and the
      method of Langham (LOBF). Correlations between the methods were identified by the
      Spearman correlation coefficient (r). LDF readings correlated with time-averaged
      mean velocity assessed by CDI in the long posterior ciliary artery (r = 0.47; p =
      0.039; n = 20), but not in the short posterior ciliary artery. LOBF measurements
      correlated with pulsatility index (PI) of CDI in short (r = 0.50; p = 0.005; n =
      30) and long posterior ciliary arteries (r = 0.41; p = 0.024; n = 30). Methods
      strengthened each other by partial correlation. The study demonstrates that CDI
      allows a more detailed insight into ocular perfusion.

PMID- 12217439
TI  - A multiscale algorithm for three-dimensional free-hand ultrasound.
AB  - This paper presents a multiscale algorithm for the reconstruction of human
      anatomy from a set of ultrasound (US) images. Reconstruction is formulated in a
      Bayesian framework as an optimization problem with a large number of unknown
      variables. Human tissues are represented by the interpolation of coefficients
      associated to the nodes of a 3-D cubic grid. The convergence of the Bayesian
      method is usually slow and initialization dependent. In this paper, a multiscale
      approach is proposed to increase the convergence rate of the iterative process of
      volume estimation. A coarse estimate of the volume is first obtained using a
      cubic grid with a small number of nodes initialized with a constant value
      computed from the observed data. The volume estimate is then recursively improved
      by refining the grid step. Experimental results are provided to show that
      multiscale method achieves faster convergence rates compared with a single-scale
      approach. This is the key improvement toward real-time implementations.
      Experimental results of 3-D reconstruction of human anatomy are presented to
      assess the performance of the algorithm and comparisons with the single-scale
      method are presented.

PMID- 12217440
TI  - Pressure-dependent attenuation in ultrasound contrast agents.
AB  - Although microbubble contrast agents are believed to respond differently under
      different driving-pressure amplitudes, few studies have been performed to
      extensively study the pressure-dependence of their properties. In this paper,
      attenuation coefficients of two contrast agents (Optison and Definity) were
      measured under different driving-pressure amplitudes using a narrowband incident
      pulse. The attenuation of both contrast agents was found to increase with
      increasing driving pressure. Simulations using the Rayleigh, Plesset, Noltingk,
      Neppiras, Poritsky (RPNNP) equation were performed to study this behavior.
      Simulation results show that significant harmonic generation at high driving
      pressure amplitudes contributes to the higher attenuation. Other possible
      explanations for this behavior were also examined. Attenuation coefficients of
      two contrast agents were also measured using a broadband method. The results
      showed great inconsistency when the center frequency of the incident broadband
      pulse was changed, indicating that broadband techniques may not be suitable for
      contrast-agent attenuation measurements.

PMID- 12217441
TI  - Dynamic noise correction for IVUS quantitative volume blood flow: methods and
      numerical validation.
AB  - In recent years, a new method to measure transverse blood flow based on the
      decorrelation of the radio-frequency (RF) signals, has been developed. Transverse
      blood flow estimation may be influenced by noise. In this paper, we investigated
      a new correlation-based method for noise correction. The decorrelation
      characteristics of transverse blood flow using an intravascular ultrasound (US)
      or IVUS array catheter were studied by means of computer modeling. Blood was
      simulated as a collection of randomly located point scatterers; moving this
      scattering medium transversely across the acoustical beam represented flow.
      Parabolic blood flow was simulated. Additive noise was added to the RF signals at
      a given signal-to-noise ratio (SNR). Next, a new method to dynamically estimate
      and suppress the decorrelation due to noise is presented. The decorrelation due
      to noise was estimated from the correlation coefficients from flowing blood
      obtained at increasing time lags. The correlation graphs are corrected for the
      decorrelation due to noise, leaving the decorrelation due to blood flow. The
      method shows promise to estimate and correct the correlation coefficients for
      noise.

PMID- 12217442
TI  - Cell-based dual snake model: a new approach to extracting highly winding
      boundaries in the ultrasound images.
AB  - Two common deficiencies of most conventional deformable models are the need to
      place the initial contour very close to the desired boundary and the incapability
      of capturing a highly winding boundary for sonographic boundary extraction. To
      remedy these two deficiencies, a new deformable model (namely, the cell-based
      dual snake model) is proposed in this paper. The basic idea is to apply the dual
      snake model in the cell-based deformation manner. While the dual snake model
      provides an effective mechanism allowing a distant initial contour, the cell
      based deformation makes it possible to catch the winding characteristics of the
      desired boundary. The performance of the proposed cell-based dual snake model has
      been evaluated on synthetic images with simulated speckles and on the clinical
      ultrasound (US) images. The experimental results show that the mean distances
      from the derived to the desired boundary points are 0.9 +/- 0.42 pixels and 1.29
      +/- 0.39 pixels for the synthetic and the clinical US images, respectively.

PMID- 12217443
TI  - Ultrasound usage and dosage in sports physiotherapy.
AB  - Ultrasound (US) therapy is the most widely available and frequently used
      electrophysical agent in physiotherapy. Despite this, there is minimal scientific
      evidence supporting its use. This raises the question of how is US being used in
      clinical practice? With a questionnaire, this study investigated US usage and
      dosage in sports physiotherapy. The results confirm the wide availability and
      frequent use of US. Applications were found to cover a wide range of clinical
      scenarios, during which therapists use a range of dosages. Two trends in dosage
      were evident and relate to the treatment of either acute or chronic conditions.
      Although rationale exists for these dosages, clinical evidence is currently
      lacking. Reasons for this lack of evidence are discussed. The results of this
      study provide a profile of US usage and dosage in sports physiotherapy and
      highlight the need for further research into its effects.

PMID- 12217444
TI  - High-frequency backscatter and attenuation measurements of porcine erythrocyte
      suspensions between 30-90 MHz.
AB  - There are now diagnostic ultrasonic imaging devices that operate at very high
      frequencies (VHF) of 20 MHz and beyond for clinical applications in
      ophthalmology, dermatology and vascular surgery. To be able to better interpret
      these images and to further the development of these devices, knowledge of
      ultrasonic attenuation and scattering of biologic tissues, such as blood, in the
      high-frequency range is crucial. VHF attenuation and backscatter experiments were
      made on porcine red blood cell (RBC) suspensions, for which much data on
      attenuation and backscatter can be found in the literature in the lower frequency
      range. Attenuation and backscatter at hematocrits of 6%, 10%, 15%, 20%, 25% and
      30% from 30 to 90 MHz were measured using a modified substitution method that
      allows the utilization of focused transducers. The results show that the
      attenuation coefficient from all suspensions increased linearly with frequency
      and the backscatter coefficient for low hematocrit suspensions was found to have
      a maximum between 10% and 15%. At higher hematocrits, a decrease in the frequency
      dependence was observed, possibly indicating that Rayleigh scattering is no
      longer valid because the wavelength in the VHF range is comparable to the size of
      a porcine RBC.

PMID- 12217445
TI  - Heterogeneous delayed enhancement of the liver after ultrasound contrast agent
      injection--a normal variant.
AB  - We report a characteristic heterogeneous delayed liver enhancement pattern that
      we have encountered in a total of 6 of approximately 1500 subjects who underwent
      contrast-enhanced liver ultrasonography. The heterogeneous enhancement occurred
      several min after contrast injection and persisted for up to 1 h. It was seen in
      diseased as well as healthy livers and appears to represent a "normal variant" of
      liver enhancement. It was observed with two different contrast agents. The cause
      of the described effect is unknown; it may be related to the formation of large
      bubbles and vascular entrapment of these bubbles in the liver.

PMID- 12217446
TI  - Test-retest reliability and validity of the Pittsburgh Sleep Quality Index in
      primary insomnia.
AB  - OBJECTIVE: Psychometric evaluation of the Pittsburgh Sleep Quality Index (PSQI)
      for primary insomnia. METHODS: The study sample consisted of 80 patients with
      primary insomnia (DSM-IV). The length of the test-retest interval was either 2
      days or several weeks. Validity analyses were calculated for PSQI data and data
      from sleep diaries, as well as polysomnography. To evaluate the specificity of
      the PSQI, insomnia patients were compared with a control group of 45 healthy
      subjects. RESULTS: In primary insomnia patients, the overall PSQI global score
      correlation coefficient for test-retest reliability was .87. Validity analyses
      showed high correlations between PSQI and sleep log data and lower correlations
      with polysomnography data. A PSQI global score > 5 resulted in a sensitivity of
      98.7 and specificity of 84.4 as a marker for sleep disturbances in insomnia
      patients versus controls. CONCLUSION: The PSQI has a high test-retest reliability
      and a good validity for patients with primary insomnia.

PMID- 12217447
TI  - Sleep disturbances, work stress and work hours: a cross-sectional study.
AB  - OBJECTIVE: The study examined the multivariate relationship between disturbed
      sleep and different work-related and background/life style factors. METHODS: 5720
      healthy employed men and women living in the greater Stockholm area participated.
      A factor analysis of eight items provided one main factor: "disturbed sleep." The
      data were analyzed using a multiple logistic regression analysis against the
      index disturbed sleep as well as the separate items "not well rested" and
      "difficulties awakening." RESULTS: The results showed that high work demands
      [odds ratio (OR) = 2.15] and physical effort at work (OR = 1.94) are risk
      indicators for disturbed sleep, while high social support is associated with
      reduced risk (OR = 0.44). In addition, higher age (45+), female gender, a high
      body mass index (BMI) and lack of exercise are background/life style risk
      indicators. Introducing into the model an item representing inability to stop
      thinking about work during free time yielded the highest OR (3.20) and forced
      work demands out of the regression. With regard to not feeling well rested, the
      same significant predictors, except physical effort, were obtained, as well as
      for having night work and being married. In addition, the age effect was reversed
      -high age predicted reduced risk of not feeling well rested. Difficulties
      awakening was predicted by high work demands, low social support, being male, low
      age and smoking. It is notable that, whereas subjective sleep quality decreased
      with age, the difficulties awakening and feelings of not being well rested after
      sleep increased with age. CONCLUSION: It was concluded that stress and the social
      situation at work are strongly linked to disturbed sleep and impaired awakening,
      that gender and, even more so, age may modify this and that the inability to stop
      worrying about work during free time may be an important link in the relation
      between stress and sleep.

PMID- 12217448
TI  - Natural course and predicting self-reported improvement in patients with chronic
      fatigue syndrome with a relatively short illness duration.
AB  - OBJECTIVE: To describe the course of fatigue in chronic fatigue syndrome (CFS)
      patients with a relatively short duration of complaints and to test which
      psychosocial factors predict spontaneous improvement 1 year later. METHODS:
      Seventy-nine patients with a complaint duration of less than 2 years were tested
      at baseline and 78 of the same group at 1-year follow-up. During this time
      period, no systematic intervention took place. Self-reported improvement and
      fatigue severity were the main outcome measures. RESULTS: Forty-six percent (95%
      confidence intervals, 95CI = 35-58%) of the patients with a short illness
      duration reported to be improved. This was a significantly (chi(2) = 20.3, P <
      .001) higher percentage compared to the 20% (95CI = 15-26%) self-reported
      improvement in a previously published natural-course study among 246 CFS patients
      with a longer illness duration. Persistence of complaints after 1-year follow-up
      was associated with high baseline levels of experienced concentration problems,
      less strong psychosocial causal explanations for the complaints, and higher
      levels of the experienced lack of social support. Baseline fatigue severity
      predicted fatigue severity at follow-up. CONCLUSION: The results showed that CFS
      patients with a relatively short duration of complaints had a more favourable
      outcome compared to patients with a long illness duration. The data also
      indicated that complete recovery only occurred in patients with a complaint
      duration of less than 15 months. This finding has important implications, since
      it suggests that after such a time period spontaneous recovery hardly occurs.

PMID- 12217449
TI  - Underlying self-esteem in chronic fatigue syndrome.
AB  - OBJECTIVE: It has been suggested that people with chronic fatigue syndrome (CFS)
      have low self-esteem; however, this is not necessarily apparent when self-esteem
      is measured overtly. This study is the first to investigate underlying self
      esteem using information-processing measures and overtly administered measures of
      self-esteem with this population. METHODS: The study comprised 68 participants
      (24 CFS, 24 healthy volunteers, and 20 chronic illness volunteers). A Self
      Statements Questionnaire (SSQ) and an Emotional Stroop Test (EST) using neutral,
      positive, and negative trait words were administered. RESULTS: Participants with
      CFS reported lower self-esteem than the two comparison groups on overt measures.
      Overt responses, however, did not fully account for the full extent of the
      interference effect from the negative word Stroop compared to the positive word
      Stroop. CONCLUSION: In contrast to previous studies, participants with CFS
      reported lower levels of self-esteem on overt measures than two comparison
      groups. It is suggested, however, that the extent to which participants reported
      low self-esteem did not fully reflect their underlying low self-esteem and that
      this may result from the use of rigidly held defence mechanisms. Further use of
      information-processing measures, in contrast to relying only on self-report
      measures, is advocated for future research.

PMID- 12217450
TI  - Attachment and coping with chronic disease.
AB  - BACKGROUND: In this clinical study, attachment theory was applied to research in
      the field of coping with chronic disease. The approach was to integrate concepts
      of coping within a framework of attachment theory. It was hypothesised that
      attachment concepts have an influence on coping strategies, and that they may
      predict the subjective emotional and physical health status during the course of
      medical treatment. METHOD: One hundred fifty patients were investigated with an
      adult attachment interview (AAPR coding system) and a coping interview (Bernese
      Coping Modes). Self-reported coping modes, social support, the subjective health
      status and quality of life were also assessed by self-report measures at two or
      more sampling points of measurement. Three subsamples of patients, suffering from
      (a) breast cancer, (b) chronic leg ulcers and (c) alopecia, were studied in order
      to include a broad range of subjective impairment caused by a disease. RESULTS:
      Findings indicate a moderate statistical effect of attachment patterns on coping
      strategies when controlling the influence of confounding variables. Insecure
      attachment was related to less flexible coping. Coping strategies also differed
      between the different types of insecure attachment; however, there were
      differences depending on the perspective of the coping behaviour (self- vs.
      observer ratings) as well. From the observer perspective, ambivalently attached
      individuals showed more negative emotional coping while avoidantly attached
      individuals showed more diverting strategies. In the self-report, ambivalently
      attached patients revealed hyperactivating tendencies in their coping behaviour
      while avoidantly attached individuals revealed deactivating tendencies.
      CONCLUSION: As a conclusion, two levels of coping should be differentiated. One
      level strongly corresponds with affect regulation, in particular the regulation
      of attachment-related emotions and concerns, while the other level shows a
      stronger tendency to outwardly oriented coping. A more secure attachment might be
      considered to be an important inner resource in the emotional adaptation to
      chronic diseases.

PMID- 12217451
TI  - Fatigue in multiple sclerosis: reciprocal relationships with physical
      disabilities and depression.
AB  - OBJECTIVE: To explore relations of fatigue, physical disabilities, and depression
      in patients with multiple sclerosis (MS) cross-sectionally and over time.
      METHODS: Ninety-eight MS patients were interviewed twice at an interval of a
      year. Relationships of physical and mental fatigue, and reduced activity and
      motivation with depression and physical disabilities were established cross
      sectionally by regression analyses and longitudinally by structural equation
      modelling. RESULTS: Cross-sectionally, physical fatigue was related with physical
      disabilities, and mental fatigue was associated with depression. Prospectively,
      physical fatigue was a predictor of the physical disabilities of a year later.
      The reverse relationship of physical disabilities predicting the physical fatigue
      of one year later was, however, not significant, while depression predicted this
      physical fatigue and reduced activity of a year later. Depression did not predict
      the later mental fatigue nor was depression predicted by preceding fatigue
      experiences. CONCLUSIONS: Fatigue in MS should be studied over time as
      relationships of fatigue with physical and mental health change during the course
      of a year. Moreover, differentiating in fatigue experiences sheds light on the
      relationship of fatigue with physical and mental health.

PMID- 12217452
TI  - Psychiatric consultation in the nursing home: referral patterns and recognition
      of depression.
AB  - OBJECTIVE: To assess the accuracy of referrals to psychiatric consultants for
      depression (or depression-related disorders) among nursing home residents.
      METHODS: Retrospective review of psychiatric consultations for nursing home
      residents in six facilities for a 3-year period. Reasons for referral, assigned
      diagnoses, rates of accuracy, sensitivity and specificity were examined to assess
      patterns of referral and recognition of clinical variants of depressive
      disorders. RESULTS: Referrals for depression comprised 19.7% of all requested
      consultations. Of patients referred for depression, 74.2% were diagnosed with a
      depressive disorder. Of all residents diagnosed with depressive disorders, 53.5%
      were referred for other reasons. Men were referred for evaluation of depression
      significantly more often than women. However, rates of diagnosis of depression
      did not appear to differ significantly between men and women. CONCLUSIONS:
      Nursing home staff often failed to recognize depression. Depressed residents are
      primarily referred for disruptive behaviors. Referrals for depression may be a
      secondary concern.

PMID- 12217453
TI  - Association between panic disorder, major depressive disorder and celiac disease:
      a possible role of thyroid autoimmunity.
AB  - OBJECTIVE: To evaluate the association between celiac disease and specific
      anxiety and depressive disorders and to identify potential common pathogenetic
      links, with particular regard to thyroid function and autoimmunity. METHODS:
      Cases included 36 adult celiac patients, 25 females and 11 males, aged 18-64
      years. Controls comprised 144 healthy subjects matched by sex and age with no
      clinical evidence or family history of celiac disease. Diagnosis of celiac
      disease was made on the basis of clinical history and serological criteria.
      Psychiatric diagnoses were formulated using the International Composite
      Diagnostic Interview, according to DSM-IV criteria. Thyroid was evaluated by
      palpation, echography and measurement of serum-free thyroid hormones (FT4, FT3),
      thyroid-stimulating hormone (TSH) and antithyroid autoantibodies (anti-TPO).
      RESULTS: Compared to controls, a significantly higher number of celiac patients
      met criteria for lifetime [15 (41.7%) versus 30 (29.8%), P < .01] and 6-month [7
      (19.4%) versus 9 (6.2%), OR = 3.2, chi(2) = 5.2, P < .05] major depressive
      disorder (MDD) and lifetime [5 (13.9%) versus 3 (2.1%), P < .001] and 6-month [3
      (8.1%) versus 2 (1.4%), P < .05] panic disorder (PD). Anti-TPO prevalence was
      significantly higher in celiac patients than in the control group (11/36 = 30.5%
      versus 14/144 = 9.7%, P < .001). A higher frequency of PD and MDD was found in
      celiac patients with positive anti-TPO when compared to negative anti-TPO
      patients (4/11 = 36.4% PD in TPO+ versus 1/25 = 4% PD in TPO-, P < .01; 9/11 =
      81.8% MD in TPO+ versus 6/25 = 9.5% MD in TPO-, P < .01). CONCLUSION: Patients
      affected by celiac disease tend to show a high prevalence of PD and MDD and
      association with subclinical thyroid disease appears to represent a significant
      risk factor for these psychiatric disorders.

PMID- 12217454
TI  - Acculturation and cardiovascular reactivity of second-generation Turkish migrants
      in Germany.
AB  - OBJECTIVE: Previous studies have shown that migration and acculturation lead to
      higher blood pressures and a higher prevalence of cardiovascular diseases.
      Heightened cardiovascular reactivity is considered as a risk factor for
      cardiovascular diseases. Therefore, the purpose of the present study was to
      examine cardiovascular reactivity in young and healthy second-generation Turkish
      migrants to Germany. METHOD: Forty-one Turkish and 20 German male students worked
      on a mental arithmetic task for 6 min and underwent the cold pressor test for 90
      s. Heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure
      (DBP) were taken in intervals of 2 min at baseline and during task periods.
      Stroke volume (SV), cardiac output (CO), preejection period (PEP), and total
      peripheral resistance (TPR) were registered continuously by impedance
      cardiography. The Turkish volunteers were divided into weak and advanced
      acculturated migrants based on self-ratings given in a questionnaire. RESULTS:
      Advanced acculturated Turkish students showed greater HR and CO increases and
      greater PEP and TPR decreases to the mental arithmetic task than Germans or weak
      acculturated Turkish students. No group differences were found for the cold
      pressor test. CONCLUSION: Migrants' acculturation is associated with an enhanced
      beta-adrenergic activation pattern of the sympathetic nervous system that might
      put them at greater risk with regards to essential hypertension and coronary
      heart disease.

PMID- 12217455
TI  - The effects of alcohol on mood induced by an emotional film: a study among women.
AB  - OBJECTIVE: The present study was designed to investigate the effects of alcohol
      on women's reactions to a negative mood-inducing stimulus. It is hypothesized
      that, like in men, alcohol also reduces tension or induces positive mood in
      women. In addition, we explored whether different mood states were affected
      differentially by alcohol intake. METHODS: Participants were 132 female students
      who were randomly divided into four groups: (1) control, (2) placebo, (3) low
      dose alcohol and (4) high-dose alcohol. A dramatic film was used to induce
      negative affect and mood was assessed at baseline, before and after the movie.
      RESULTS: Alcohol consumption decreased the negative impact of the emotional film
      on mood. Some mood states varied with pharmacological changes, while others
      varied with expectancy of drinking alcohol. Relaxation, fear and sadness were not
      differentially affected by alcohol intake or expectancy. CONCLUSION: Drinking
      when exposed to emotional situations may be reinforced by the short-term positive
      effects on well-being among moderate female drinkers. The findings further
      suggest that the effects of alcohol on certain specific emotional states
      (including sadness and fear) are minimal at best.

PMID- 12217456
TI  - Medical (fluoxetine) and psychological (cognitive-behavioural therapy) treatment
      for premenstrual dysphoric disorder: a study of treatment processes.
AB  - OBJECTIVES: To investigate (i) the differential changes in premenstrual symptoms,
      mood, cognitions, and coping strategies during two treatments [cognitive
      behavioural therapy (CBT) and fluoxetine] for premenstrual dysphoric disorder
      (PMDD) and (ii) the characteristics of those with good vs. poor outcome post
      treatment and at 1 year follow-up. METHODS: Premenstrual symptoms, mood (Hospital
      Anxiety and Depression Scale, HADS), causal attributions, and use of cognitive
      and behavioural coping strategies were examined during 6 months of both
      treatments. The two treatment groups were then combined and divided on the basis
      of good vs. poor outcome posttreatment and at 1 year follow-up. Baseline measures
      were used to predict posttreatment outcome, and baseline and posttreatment
      measures were examined when attempting to predict outcome at 1 year follow-up.
      RESULTS: Both treatments were equally effective at the end of 6 months
      (prospective daily diary measure). Fluoxetine treatment had a more rapid effect
      and greater impact upon anxiety symptoms, while CBT was associated with increased
      use of cognitive and behavioural coping strategies and a shift from a biomedical
      to a biopsychosocial causal attribution of premenstrual symptoms. Depressed mood
      at baseline assessment was associated with poorer response to both treatments,
      and learning active behavioural coping strategies was associated with a good
      outcome at 1 year follow-up. CONCLUSION: These results provide evidence of
      differential treatment effects of fluoxetine and CBT for PMDD and offer
      information that will enhance clinical decision-making.

PMID- 12217457
TI  - Problems reported by self-harm patients: perception, hopelessness, and suicidal
      intent.
AB  - OBJECTIVE: Research suggests that problem-solving therapy may be an effective
      intervention following self-harm. This study determines the relation between self
      harm patients' perceptions of their problems and their expressions of
      hopelessness and suicidal intent. METHOD: One hundred fifty patients admitted to
      a district hospital following self-harm were asked questions about the type and
      perceived solubility of their problems. In addition, in each case, the patient
      completed a Beck's hopelessness scale and a psychiatrist completed a Beck's
      suicidal intent scale. RESULTS: 66% of patients, and more of the males than of
      the females, recorded at least one problem that they believed to be insoluble;
      such problems were most often in the area of relationships. Patients who reported
      insoluble problems experienced higher levels of hopelessness and more suicidal
      intent. There was significant correlation among the number of insoluble problems,
      hopelessness, and suicidal intent. CONCLUSIONS: People who undertake self-harm
      report insoluble relationship problems. When assessing hopelessness and suicidal
      intent in self-harm patients, clinicians should ask about perception of insoluble
      problems.

PMID- 12217458
TI  - The relationship of alexithymia to pain severity and impairment among patients
      with chronic myofascial pain: comparisons with self-efficacy, catastrophizing,
      and depression.
AB  - OBJECTIVE: Alexithymia is elevated among patients with chronic pain, but the
      relationship of alexithymia to the severity of pain among chronic pain patients
      is unclear. Also, studies have rarely examined whether alexithymia is unique from
      other, more widely studied constructs in the chronic pain literature (i.e., self
      efficacy, catastrophizing, and depression), and research has not examined how
      alexithymia relates to the sensory versus affective dimensions of pain. METHODS:
      Among 80 patients with chronic myofascial pain, we tested how alexithymia
      (Toronto Alexithymia Scale-20) was related to three competing constructs--self
      efficacy, catastrophizing, and depression--and to the sensory and affective
      dimensions of pain as well as physical impairment. We then determined whether
      alexithymia remained correlated with pain and impairment when tested
      simultaneously with each of the three competing constructs. RESULTS: Analyses
      controlled for patients' sex, age, marital status, and duration of pain.
      Alexithymia was moderately correlated with less self-efficacy and greater
      catastrophizing, and substantially correlated with greater depression.
      Alexithymia was positively related to both affective pain and physical
      impairment, but was unrelated to sensory pain, whereas all three of the competing
      constructs were related to both types of pain as well as physical impairment.
      Regression analyses indicated that alexithymia remained a significant and
      independent correlate of affective pain severity while controlling for either
      self-efficacy or catastrophizing, but depression accounted for alexithymia's
      relationship with affective pain. Also, alexithymia was no longer related to
      physical impairment, after controlling for any of the other three constructs.
      CONCLUSION: Although alexithymia is not related to the sensory component of pain,
      it is correlated positively with the affective or unpleasantness component of
      pain, independent of self-efficacy or catastrophizing. The emotional regulation
      deficits of alexithymia may lead to depression, which appears to mediate
      alexithymia's relationship to affective pain. Alexithymia's relationship with
      physical impairment appears to be better accounted for by self-efficacy or
      catastrophizing.

PMID- 12217459
TI  - A population study of anxiety and depression among persons who report whiplash
      traumas.
AB  - The purpose of this study was to explore whether self-reported whiplash traumas
      were associated with increased prevalence of anxiety disorder and depression. A
      cross-sectional design (N = 61,110) based on data from the health study (HUNT-II)
      was used. Anxiety and depression were measured with the Hospital Anxiety and
      Depression Scale (HADS). A positive association was found between whiplash
      traumas and anxiety disorder and depression in traumas that happened more than 2
      years ago, but not in more recent whiplash traumas. Some of the association
      between whiplash traumas and anxiety and depression is due to neck pain and
      headache. Two different explanations, the "memory bias" and the "attribution"
      hypothesis, are discussed as explanations of these results.

PMID- 12217464
TI  - Unenhanced helical CT scanning of the abdomen and pelvis changes disposition of
      patients presenting to the emergency department with possible acute appendicitis.
AB  - This study sought to determine if obtaining an unenhanced abdominopelvic computed
      tomography (UHCT) scan alters the disposition of patients presenting to the
      Emergency Department (ED) with signs and symptoms of acute appendicitis. A
      convenience sample of 101 patients presenting with a clinical picture suggestive
      of appendicitis were prospectively enrolled. Emergency physicians (EPs) and
      general surgeons independently recorded their anticipated disposition of each
      patient as: discharge, admit for observation, or admit for appendectomy. A UHCT
      scan was then obtained and the patient's ultimate disposition recorded. EPs
      altered their dispositions after UHCT scanning in 35 patients (34.7%, 95% CI
      25.4% to 44.0%), and general surgeons altered their dispositions in 27 patients
      (26.7%, 95% CI 18.1% to 35.3%). More patients underwent operative intervention
      than were originally selected by EPs [14 additional patients, (13.9%, 95% CI 7.1%
      to 20.6%)] or by surgeons [20 additional patients, (19.8%, 95% CI 12.0% to
      27.6%)]. CT scan revealed alternative diagnoses in 20 patients (19.8%). UHCT
      scanning significantly alters patient disposition, and significantly increases
      the number of operative interventions performed in patients with suspected
      appendicitis. UHCT scanning may also identify alternate pathology that clinically
      mimics appendicitis.

PMID- 12217465
TI  - Appendiceal enlargement as a criterion for clinical diagnosis of acute
      appendicitis: is it reliable and valid?
AB  - The purpose of this study was to evaluate appendiceal enlargement as a
      radiographic criterion for the diagnosis of acute appendicitis. We examined
      medical records and specimens of 190 adults and children who presented to a
      teaching hospital in New York City with right-lower-quadrant pain and who
      underwent surgery. Computed tomography (CT), clinical evaluation (based on
      Alvarado's predictive model) and pathologic data of these 190 cases revealed that
      appendiceal enlargement might in some cases represent a normal anatomic variant
      of a vermiform appendix and that the lack of a dilated lumen and thickened wall
      did not necessarily establish the absence of inflammation. Yet, radiologic
      evidence of appendix size often influences the diagnosis and management of
      patients with acute abdominal pain, including the decision to operate. This
      tendency to equate an enlarged appendix with appendicitis is shown to lead to an
      inappropriate diagnosis and jeopardize optimal care of patients with acute
      abdominal pain.

PMID- 12217466
TI  - Acute appendicitis in a femoral hernia: an unusual presentation of a groin mass.
AB  - Although most groin masses are simple hernias, occasionally these hernias contain
      more than just small intestine. Femoral hernias, which are less common than
      inguinal, are more often found in females. Stomach, omentum, colon, or an
      appendix each has been reported to be contained in a femoral hernia. Having an
      acutely inflamed appendix contained in a femoral hernia sac in a male is
      extraordinarily rare. We report a case of acute appendicitis contained in a
      femoral hernia of a 76 year old man. This entity presents much like an
      incarcerated hernia, and differentiating the two can lead to changes in the
      surgical management.

PMID- 12217467
TI  - Pyelocalyceal diverticulum: an unusual cause of acute renal colic.
AB  - The differential diagnosis of acute flank pain includes kidney stones, urinary
      tract infection, dissecting abdominal aortic aneurysm (AAA), arterial or venous
      compromise of the kidney, renal abscess, renal carcinoma, and papillary necrosis.
      This is a report of an unusual cause of renal colic: pyelocalyceal diverticulum.
      Stasis of urine within a diverticulum promotes both calculus formation and
      urinary tract infection, either of which can lead to colic. Several radiographic
      findings may suggest a calyceal diverticulum, including, on plain X-ray, a very
      peripheral or mobile renal calculus, or on intravenous pyelogram, an early
      filling-defect and delayed or retained filing of a circular or ovoid mass.

PMID- 12217469
TI  - Toothpick injury mimicking renal colic: case report and systematic review.
AB  - We describe a case of a patient with left flank pain that was caused by a
      perforation in the splenic flexure of the colon by a toothpick. We conducted a
      systematic review of the literature to examine the nature of injuries caused by
      ingested toothpicks. Articles were analyzed for the following outcome variables:
      presenting complaint, site of injury, recollection of toothpick ingestion, time
      to presentation, findings from imaging studies, and mortality. Most patients
      (70%) presented with abdominal pain. Few patients (12%) remember swallowing a
      toothpick. The onset of symptoms ranged from <1 day to 15 years. Toothpicks
      caused perforation most frequently at the duodenum and the sigmoid. In some
      cases, toothpicks migrated outside the gastrointestinal tract and were found in
      the pleura, pericardium, ureter, or bladder. Toothpicks were apparent on imaging
      studies in 14% of the cases. The definitive diagnosis was most commonly made at
      laparotomy (53%), followed by endoscopy (19%). Overall mortality was 18%.
      Ingested toothpicks may cause significant gastrointestinal injuries, and must be
      treated with caution.

PMID- 12217468
TI  - Malaria: a rising incidence in the United States.
AB  - Malaria is frequently a deadly disease, particularly in tropical countries of the
      world where this protozoan infection is endemic. While physicians in tropical
      countries are familiar with the presentation, those who do not practice in
      endemic regions of the world may neglect to add tropical diseases to their
      differential diagnosis of fever. Epidemiologic data from the CDC show the number
      of cases of malaria being diagnosed in the United States in the last decade has
      risen sharply. With international travel continuing to rise, there is strong
      reason to consider malaria as a source of fever.

PMID- 12217470
TI  - Blunt diaphragmatic injury in a 7-year-old girl.
AB  - Blunt diaphragmatic injury is notoriously difficult to diagnose. There is no gold
      standard for radiologic diagnosis of this disease entity. This article reports a
      case of traumatic diaphragmatic rupture in a 7-year-old girl whose injury was
      identified on hospital day 2. The discussion includes a review of the physiology
      of this injury and the utility of radiologic modalities in making a timely
      diagnosis.

PMID- 12217471
TI  - Eight minutes or less: does the ambulance response time guideline impact trauma
      patient outcome?
AB  - Emergency Medical Services (EMS) agencies are increasingly being held to an
      ambulance response time (RT) criterion of responding to a medical emergency
      within 8 min for at least 90% of calls. This recommendation resulted from one
      study of outcome after nontraumatic cardiac arrest and has never been studied for
      any other emergency. This retrospective study evaluates the effect of exceeding
      the 8 min RT guideline on patient survival for victims of traumatic injury
      treated by an urban paramedic ambulance EMS system and transported to a single
      Level I trauma center. Of 3576 patients identified by the hospital trauma
      registry, 3490 (97.6%) had complete records available. Patients were grouped
      according to ambulance RT: < or = 8 min (n = 2450) or > 8 min (n = 1040). After
      controlling for other significant predictors, there was no difference in survival
      after traumatic injury when the 8 min ambulance RT criteria was exceeded
      (mortality odds ratio 0.81, 95% CI 0.43-1.52). There was also no significant
      difference in survival when patients were stratified by injury severity score
      group. Exceeding the ambulance industry response time criterion of 8 min does not
      affect patient survival after traumatic injury.

PMID- 12217472
TI  - The esophageal detector bulb in the aeromedical setting.
AB  - To determine the accuracy of the Esophageal Detector Bulb (EDB) in the
      aeromedical setting, we conducted a prospective, observational study of all
      intubated patients transported by an aeromedical program over two years. Flight
      personnel recorded the results of the EDB, clinical examination, pulse oximetry,
      and capnography (ETCO(2)). Endotracheal tube position was confirmed by
      prehospital ETCO(2) or by the receiving emergency physician. There were 104 EDB
      assessments in 53 patients. The EDB correctly identified four of five esophageal
      intubations and 96 of 99 tracheal intubations. The sensitivity and specificity of
      the EDB in the detection of an esophageal intubation were 80% (95% CI, 38-96%)
      and 97% (95% CI, 92-99%), respectively, and the overall accuracy was 96% (95% CI,
      90-98%). The EDB augments the ability of an aeromedical crew to determine
      endotracheal tube position, but its results must be carefully interpreted in the
      context of other available means of confirmation of endotracheal tube position.

PMID- 12217473
TI  - Cardiac troponins.
AB  - Cardiac troponins I and T are proteins integral to the function of cardiac
      muscle. They are very sensitive markers for the detection of myocardial damage,
      and the ability to assay their serum levels accurately and quickly have
      revolutionized the concepts of minor myocardial injury and infarction. They are
      also powerful prognostic indicators of future adverse cardiac events.
      Limitations, more of troponin T than I, include decreased specificity in renal
      failure and skeletal muscle disease. Rapid, whole blood assays are now available
      that can be done at the patient's bedside. This review discusses the cardiac
      troponins, their biochemistry, the assays for them currently available, and their
      roles in the evaluation of cardiac disease in the Emergency Department (ED).

PMID- 12217474
TI  - Distinguishing traumatic lumbar puncture from true subarachnoid hemorrhage.
AB  - The lumbar puncture (LP) is a relatively simple diagnostic test. However,
      significant diagnostic ambiguity can arise when trauma from the needle causes
      bleeding into the subarachnoid space, especially when trying to make the
      diagnosis of subarachnoid hemorrhage (SAH). The purpose of this article is to
      assist emergency physicians in distinguishing traumatic LPs from SAH. To
      correctly interpret the findings of a traumatic tap, a few concepts must be
      understood. Timing of the LP in relation to the onset of the SAH affects the
      results of the cerebrospinal fluid (CFS) analysis; the typical findings will
      change with time. With a few caveats, xanthochromia, the yellow discoloration of
      the CSF resulting from hemoglobin catabolism, is often critical in making a
      diagnosis of SAH. A few of the most essential methods for distinguishing
      traumatic LP from true SAH include: the "three tube test," opening pressure, and
      inspection for visual xanthochromia.

PMID- 12217475
TI  - Pediatric tremors.

PMID- 12217476
TI  - Cystic lesion in the chest.

PMID- 12217477
TI  - Emergency department presentation of spontaneous rupture of hepatocellular
      carcinoma.

PMID- 12217478
TI  - Preoperative diagnosis of obturator hernia.

PMID- 12217479
TI  - Evaluation of a teaching laboratory using a cadaver model for tube
      thoracostomy(1).
AB  - A prior study evaluated the efficacy of a dog laboratory to teach residents chest
      tube thoracostomy. This study evaluated a similarly structured program using
      human cadavers. A prospective repeat measure study of chest tube thoracostomy
      placement training was performed in a university laboratory setting using human
      cadavers. Ten Emergency Medicine residents were given a written pretest, followed
      by training. Resident attempts were then timed. The following day, a repeat test
      was administered. Three weeks later, a third written post-test was conducted. The
      written test scores improved for every participant. Mean times for procedure
      completion improved from 86 sec to 34 sec during the first session, and remained
      stable over 4 attempts from 30 sec to 32 sec during the second session. This
      approach to teaching clinical procedures should be considered for Emergency
      Medicine residency programs and for continuing education courses that emphasize
      procedural skills.

PMID- 12217481
TI  - HRT and SERMs: the good, the bad...and the lovely?
AB  - Recent studies have provided strong evidence that the biological activity of
      selective estrogen-receptor modulators (SERMs) depends on the conformation of the
      SERM-receptor complex, the estrogen-receptor-signaling mechanism, and the tissue
      co-regulator composition. In addition to these new observations, other studies
      convincingly demonstrate that estrogen has cardioprotective properties, favorably
      regulating genes that are crucial to vascular physiology. These novel findings
      could thus be key to generating SERMs that solve the risks currently associated
      with hormone replacement therapy. In addition, further development could result
      in SERMs that possess not only anti-estrogenic actions in the breast and uterus,
      but also estrogenic protective actions in bone and the cardiovascular system.

PMID- 12217482
TI  - Talking the talk: the role of VEGF proteins in cell signaling.
AB  - Vascular endothelial growth factors (VEGFs) stimulate endothelial cell growth
      through interactions with their tyrosine kinase receptors to stimulate
      intracellular signaling events. This culminates in the expression of specific
      gene products that induce a cellular response in numerous physiological
      processes, including hematopoeisis, oncogenesis and embryogenesis. The primordial
      function of VEGF can be revealed by studying VEGF-mediated signaling pathways in
      the powerful and tractable model system, Drosophila melanogaster, which has
      proved invaluable in furthering our understanding of conserved developmental
      themes.

PMID- 12217483
TI  - Sex, hormones and the cardiovascular system.
AB  - The meeting "Sex Differences in Cardiovascular Health and Disease" was held in
      Madison, WI USA, on 24 July 2002.

PMID- 12217488
TI  - The GH-IGF-I axis in children with idiopathic short stature.
AB  - Idiopathic short stature (ISS) is a term used for children in whom the etiology
      of the short stature is undefined. Investigations of the growth hormone (GH)
      insulin-like growth factor I axis have revealed several molecular and
      endocrinological defects in ISS patients. Abnormalities of GH secretion and
      action, although not frequent, will help to categorize some children with ISS.
      Because most diagnostic methods remain crude, however, their modification might
      be necessary to identify more subtle and yet functionally significant
      abnormalities of this endocrine axis.

PMID- 12217489
TI  - Peroxisome proliferator-activated receptor-gamma in macrophage lipid homeostasis.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma), a fatty acid
      receptor, has received particular attention as the molecular target of insulin
      sensitizing drugs, and as a regulator of lipid accumulation by the coronary
      artery macrophages known as foam cells. Controversial results have been reported
      regarding the consequences of PPARgamma activation in the inflammatory response,
      the progression or improvement of the atherosclerotic lesion, and the identity of
      target tissues (muscle or fat) for PPARgamma-specific antidiabetic drugs. A clear
      understanding of how PPARgamma functions in each of these processes is therefore
      necessary to advance its utility as a therapeutic target. Receptor-dependent and 
      independent actions of PPARgamma agonists have been carefully examined with a
      combination of Pparg-knockout mice, PPARgamma-null embryonic stem cells,
      PPARgamma-specific drugs, and mouse models of atherosclerosis. Through those
      combined studies, a physiological and therapeutic role for PPARgamma in lipid
      management by the macrophage has emerged.

PMID- 12217490
TI  - Lessons from constitutively active mutants of G protein-coupled receptors.
AB  - In the past decade, the concept of constitutive activity has profoundly modified
      our understanding of G protein-coupled-receptors (GPCRs). Here, we review the
      contribution of constitutively active mutants (CAMs) to our understanding of
      three aspects of GPCR physiopathology: (1) GPCR activation is a complex mechanism
      involving both the release of inactive state conformational constraints, mimicked
      by most CAMs, and the creation of new interactions that stabilize the active
      state and are mimicked by a restricted set of CAMs; (2) GPCR phosphorylation,
      internalization and desensitization processes are activated by receptor
      conformations, which partly overlap those activating G protein; (3) natural CAMs,
      mostly affecting GPCRs of the endocrine system, are found in several hereditary
      and acquired diseases, including cancers. One major remaining question is how
      CAMs recapitulate the different structural modifications of the agonist-induced
      active conformation(s) of the wild-type receptor. This characterization is a
      prerequisite for further use of CAMs as ligand-free models of active GPCRs in
      structural, cellular and physiological studies.

PMID- 12217491
TI  - Relaxin peptides are new global players.
AB  - Relaxin (RLX) has come of age. From being one of the earliest hormones described
      with a very specific function in parturition, recent research has now shown that
      it is involved in a variety of roles, from endometrial differentiation during
      embryo implantation, to being a response factor in infarct and wound situations.
      It ameliorates fibrosis, and might also be involved in tumour growth and
      progression. And it is not alone: two other closely related peptide hormones have
      recently been identified, one specific for the brain, the other with roles in
      testicular descent and ovarian apoptosis. Finally, the recent cloning of the RLX
      receptors now provides the basis for a new molecular pharmacology for these
      peptide hormones, and preliminary studies suggest that their signal transduction
      is both interesting and unusual.

PMID- 12217493
TI  - Aquaporins and disease: lessons from mice to humans.
AB  - Recent discovery of a family of water-specific membrane channel proteins, the
      aquaporins, has provided new insights into the molecular basis of membrane water
      permeability. Eleven mammalian aquaporins have been identified to date, with
      homolog present across the spectrum of life, including bacteria, yeast and
      plants. The distribution of the mammalian aquaporins predicts their participation
      in a range of pathophysiological events. Empirical evidence of a physiological
      role for aquaporins is emerging from studies in both mice and humans, and
      suggests that aquaporins are likely to play significant roles in human
      pathophysiology.

PMID- 12217492
TI  - Estrogen action and cytoplasmic signaling cascades. Part I: membrane-associated
      signaling complexes.
AB  - Remarkable progress in recent years has suggested that estrogen action in vivo is
      complex and often involves activation of cytoplasmic signaling cascades in
      addition to genomic actions mediated directly through estrogen receptors alpha
      and beta. Rather than a linear response mediated solely through estrogen
      responsive DNA elements, in vivo estrogen might simultaneously activate distinct
      signaling cascades that function as networks to coordinate tissue responses to
      estrogen. This complex signaling system provides for exquisite control and
      plasticity of response to estrogen at the tissue level, and undoubtedly
      contributes to the remarkable tissue-specific responses to estrogens. In part I
      of this series, we summarize cytoplasmic signaling modules involving estrogen or
      estrogen receptors, with particular focus on recently described membrane
      associated signaling complexes.

PMID- 12217497
TI  - Salmonella selectively stops traffic: response from Chakravortty and Hensel.

PMID- 12217496
TI  - Salmonella selectively stops traffic.
AB  - The intracellular pathogen Salmonella replicates in infected host cells within a
      specialized vacuole referred to as the Salmonella-containing vacuole (SCV).
      Effector molecules encoded by the Salmonella pathogenicity island 2 (SPI-2) type
      III secretion system (TTSS) are essential for Salmonella to survive in the
      intracellular environment. It was previously shown that SPI-2 allows Salmonella
      to inhibit the recruitment of NADPH phagocyte oxidase-containing vesicles to
      SCVs. New research has now revealed that SPI-2 effectors also interfere with the
      colocalization of inducible nitric oxide synthase (iNOS) to SCVs, thus protecting
      the pathogen from the antimicrobial actions of reactive nitrogen species.

PMID- 12217498
TI  - Is there a role for replication fork asymmetry in the distribution of genes in
      bacterial genomes?
AB  - Replication generates bacterial chromosomes with strands that differ in the
      number of genes and base composition. It has been suggested that in bacteria such
      as Bacillus subtilis, PolC is responsible for the synthesis of the leading strand
      and DnaE for the lagging strand, whereas in many other bacteria DnaE is
      responsible for the synthesis of both strands. Here, I show that the possession
      of PolC correlates with leading strands that contain an average of 78% of genes
      compared with 58% for genomes that do not contain PolC. This suggests that
      asymmetrical replication forks could have a major role in defining and
      constraining the structure of the bacterial chromosome. The presence of PolC is
      not correlated with compositional strand bias, suggesting that the two biases
      result from different types of structural asymmetry.

PMID- 12217499
TI  - Sibling rivalry.

PMID- 12217504
TI  - Does multiple infection select for raised virulence?
AB  - Classical models of virulence evolution conclude that the increased competition
      favoured by multiple infection will select for increasing consumption and
      deterioration of the host resource, or 'virulence'. However, recent empirical and
      theoretical studies suggest that this view of virulence has some shortcomings.
      Here, we argue that the evolutionary consequences of multiple infection depend
      critically on whether the exploitation rate of an individual parasite is governed
      directly by the behaviour of the individual, or whether it is limited by the
      collective behaviour of the coinfecting group. We illustrate that, depending on
      the mechanistic details of exploitation, multiple infection can select for
      reduced virulence.

PMID- 12217505
TI  - The alveolar macrophage: the Trojan horse of Bacillus anthracis.
AB  - Bacillus anthracis, the causative agent of anthrax, has a particular strategy for
      invading the host and crossing the alveolar barrier. B. anthracis survives within
      alveolar macrophages, after germination within the phagolysosome, then enters the
      external medium where it proliferates. Recent data have shown that edema toxin
      and lethal toxin are the major genetic determinants mediating the survival of
      germinated spores within macrophages. Here, recent advances in the analysis of B.
      anthracis pathogenesis are summarized and future challenges discussed.

PMID- 12217506
TI  - Nutrient dynamics in the deep blue sea.
AB  - For more than a century, oceanographers have studied the interactions between the
      photosynthetic production of organic matter and nutrient dynamics in the sea.
      This research has been field-oriented and transdisciplinary, occurring at the
      intersections of research in microbiology, physics, analytical chemistry, cell
      physiology and ecology. The global database derived from this collective effort
      established a sound scientific understanding of nutrient dynamics and the vital
      role of microorganisms, both autotrophic and heterotrophic, in the coupled
      organic-matter production and decomposition cycles in the sea. However, novel
      approaches used over the past two decades, including new designs for field
      experiments, repeat field observations and remote-sensing capabilities, together
      with updated methods of sample analysis, have led to a revolution in our thinking
      about the mechanisms and controls of nutrient dynamics in the deep blue sea.
      Contemporary paradigms bear only partial resemblance to the dogma of the past,
      and are likely to evolve further as new data and new ideas are presented for open
      discussion and debate.

PMID- 12217507
TI  - Exploitation of the endoplasmic reticulum by bacterial pathogens.
AB  - The endoplasmic reticulum (ER) has unique properties that are exploited by
      microbial pathogens. Exotoxins secreted by bacteria take advantage of the host
      transport pathways that deliver proteins from the Golgi to the ER. Transport to
      the ER is necessary for the unfolding and translocation of these toxins into the
      cytosol where their host targets reside. Intracellular pathogens subvert host
      vesicle transport to create ER-like vacuoles that support their intracellular
      replication. Investigations on how bacterial pathogens can use the ER during host
      infection are providing important details on transport pathways involving this
      specialized organelle.

PMID- 12217508
TI  - Dendritic cells and the complexity of microbial infection.
AB  - Dendritic cells (DCs) can discriminate between different classes of
      microorganisms, present antigens to T cells and initiate innate and adaptive
      immune responses. DCs do not act individually, and their function can be fine
      tuned by environmental and tissue factors as well as by the microorganisms
      themselves. Recent studies have reported DCs can integrate stimuli derived from
      microbial pathogens and other cells present at, or recruited to, the site of
      infection. These interactions can determine the success or failure of the immune
      response induced against pathogens.

PMID- 12217512
TI  - Peering inside lipid rafts and caveolae.
AB  - Clustering of proteins into membrane microdomains, such as lipid rafts and
      caveolae, could act as a mechanism for regulating cell signaling and other
      cellular functions. Certain lipid modifications are hypothesized to target
      proteins to these domains on the cytoplasmic leaflet of the plasma membrane. This
      concept has now been tested in living cells using an assay sensitive to the
      lateral distribution of proteins in membranes over sub-micron distances.

PMID- 12217513
TI  - The PASTA domain: a beta-lactam-binding domain.
AB  - The PASTA domain (for penicillin-binding protein and serine/threonine kinase
      associated domain) is found in the high molecular weight penicillin-binding
      proteins and eukaryotic-like serine/threonine kinases of a range of pathogens. We
      describe this previously uncharacterized domain and infer that it binds beta
      lactam antibiotics and their peptidoglycan analogues. We postulate that PknB-like
      kinases are key regulators of cell-wall biosynthesis. The essential function of
      these enzymes suggests an additional pathway for the action of beta-lactam
      antibiotics.

PMID- 12217514
TI  - The novel EPTP repeat defines a superfamily of proteins implicated in epileptic
      disorders.
AB  - Recent studies suggest that mutations in the LGI1/Epitempin gene cause autosomal
      dominant lateral temporal epilepsy. This gene encodes a protein of unknown
      function, which we postulate is secreted. The LGI1 protein has leucine-rich
      repeats in the N-terminal sequence and a tandem repeat (which we named EPTP) in
      its C-terminal region. A redefinition of the C-terminal repeat and the
      application of sensitive sequence analysis methods enabled us to define a new
      superfamily of proteins carrying varying numbers of the novel EPTP repeats in
      combination with various extracellular domains. Genes encoding proteins of this
      family are located in genomic regions associated with epilepsy and other
      neurological disorders.

PMID- 12217519
TI  - An "integrated model" of programmed ribosomal frameshifting.
AB  - Many viral mRNAs, including those of HIV-1, can make translating ribosomes change
      reading frame. Altering the efficiencies of programmed ribosomal frameshift (PRF)
      inhibits viral propagation. As a new target for potential antiviral agents, it is
      therefore important to understand how PRF is controlled. Incorporation of the
      current models describing PRF into the context of the translation elongation
      cycle leads us to propose an 'integrated model' of PRF both as a guide towards
      further characterization of PRF at the molecular and biochemical levels, and for
      the identification of new targets for antiviral therapeutics.

PMID- 12217520
TI  - Powering the peptide pump: TAP crosstalk with energetic nucleotides.
AB  - ATP-binding cassette (ABC) transporters represent a large family of membrane
      spanning proteins that have a shared structural organization and conserved
      nucleotide-binding domains (NBDs). They transport a large variety of solutes, and
      defects in these transporters are an important cause of human disease. TAP
      (tmacr;ransporter associated with antigen pmacr;rocessing) is a heterodimeric ABC
      transporter that uses nucleotides to drive peptide transport from the cytoplasm
      into the endoplasmic reticulum lumen, where the peptides then bind major
      histocompatibility complex (MHC) class I molecules. TAP plays an essential role
      in the MHC class I antigen presentation pathway. Recent studies show that the two
      NBDs of TAP fulfil distinct functions in the catalytic cycle of this transporter.
      In this opinion article, a model of alternating ATP binding and hydrolysis is
      proposed, in which nucleotide interaction with TAP2 primarily controls substrate
      binding and release, whereas interaction with TAP1 controls structural
      rearrangements of the transmembrane pathway. Viral proteins that inhibit TAP
      function cause arrests at distinct points of this catalytic cycle.

PMID- 12217521
TI  - The PTEN, Mdm2, p53 tumor suppressor-oncoprotein network.
AB  - Oncoproteins and tumor-suppressor proteins regulate cell growth and viability.
      Recent observations show that phosphoinositide 3-kinase (PtdIns 3-kinase)-Akt
      signaling promotes the phosphorylation and movement of the Mdm2 oncoprotein into
      the nucleus, where it downregulates the p53 tumor-suppressor protein. The PTEN
      tumor suppressor protein inhibits activation of Akt and this restricts Mdm2 to
      the cytoplasm. Restriction of Mdm2 to the cytoplasm promotes p53 function and
      thereby sustains the sensitivity of cancer cells to chemotherapy. p53 acutely
      induces Mdm2, providing damaged cells the opportunity for repair, but
      subsequently induces PTEN, favoring the death of mutated or irrevocably damaged
      cells. Thus, oncoproteins and tumor suppressor proteins are networked to promote
      normal cell function and eliminate mutated cells.

PMID- 12217522
TI  - Polyunsaturated fatty acid synthesis: what will they think of next?
AB  - Polyunsaturated fatty acids have crucial roles in membrane biology and signaling
      processes in most living organisms. However, it is only recently that molecular
      genetic approaches have allowed detailed studies of the enzymes involved in their
      synthesis. New evidence has revealed a range of pathways in different organisms.
      These include a complex sequence for synthesis of docosahexaenoic acid (22:6) in
      mammals and a polyketide synthase pathway in marine microbes.

PMID- 12217523
TI  - A universal role for MyD88 in TLR/IL-1R-mediated signaling.
AB  - The MyD88 adapter protein links members of the toll-like receptor (TLR) and
      interleukin-1 receptor (IL-1R) superfamily to the downstream activation of
      nuclear factor-kappaB and mitogen-activated protein kinases. Although originally
      identified as a myeloid-differentiation marker, MyD88 is now known to play an
      essential role in the innate immune response of insects and mammals. The
      generation of MyD88-deficient mice, as well as the identification of MyD88
      related proteins and regulators of MyD88 signaling, has revealed new and
      important insights into the function of MyD88.

PMID- 12217524
TI  - The rise of ROS.

PMID- 12217593
TI  - Complete hepatic regeneration after somatic deletion of an albumin-plasminogen
      activator transgene. 1991.

PMID- 12217594
TI  - Clofibrate improves glucose tolerance in fat-fed rats but decreases hepatic
      glucose consumption capacity.
AB  - BACKGROUND/AIMS: High-fat (HF) diets cause glucose intolerance. Fibrates improve
      glucose tolerance. We have tried to obtain information on possible hepatic
      mechanisms contributing to this effect. METHODS: Rats were fed a HF diet,
      isocaloric with the control diet, for 3 weeks without or with clofibrate. Several
      parameters related to liver glucose and glycogen metabolism were measured.
      RESULTS: Clofibrate prevented the induction of glucose intolerance by 3 weeks HF
      feeding. Improved glucose tolerance by clofibrate was not due to increases in
      glucose phosphorylation or glycolysis in the liver, since both the HF diet and
      clofibrate suppressed glucokinase and pyruvate kinase activities with no effect
      on glucose 6-phosphatase. Clofibrate decreased glycogen storage in both control
      and HF rats. Clofibrate, with and without HF feeding, inhibited weight gain
      during the experimental period. Body temperature was significantly elevated by
      clofibrate, indicative of an increased basal metabolic rate. The capacity of
      liver mitochondria to oxidize long-chain fatty acids increased by clofibrate
      treatment. Mitochondria did not show uncoupling. CONCLUSIONS: Clofibrate does not
      improve glucose tolerance by improving hepatic glucose or glycogen metabolism.
      Peripheral glucose oxidation may be facilitated by increased energy dissipation.

PMID- 12217595
TI  - Differential modulation of insulin actions by dexamethasone: studies in primary
      cultures of adult rat hepatocytes.
AB  - BACKGROUND/AIMS: Steroid diabetes is associated with hepatic insulin resistance;
      in hepatic cell models, however, mainly insulin-permissive effects have been
      described. Here we investigate modulation by dexamethasone of a larger number of
      insulin actions. METHODS: Adult rat hepatocytes were cultured+/-dexamethasone for
      48 h; insulin actions were studied subsequently. RESULTS: Stimulation of
      glycolysis by insulin but not by glucose required culture with dexamethasone.
      Activation of glycogen synthesis by insulin or glucose was strongly enhanced by
      dexamethasone, the insulin effects on glycogenolysis and amino acid uptake were
      not modulated. When dexamethasone was omitted from the culture, insulin was
      incapable to activate glycogen synthase, inactivate glycogen phosphorylase or
      elevate the level of fructose 2,6-bisphosphate. Dexamethasone did not alter
      insulin binding, insulin receptor number or kinase activity, insulin receptor
      substrate-1 and Akt protein expression/phosphorylation. Insulin-stimulated
      association of phosphatidylinositol 3-kinase with insulin receptor substrates-1
      and -2 was increased with dexamethasone, the increased association with IRS-2
      may, at least partially, be explained by higher IRS-2 protein expression.
      CONCLUSIONS: The steroid does not cause hepatic resistance in vitro. The
      differential attenuation under steroid deprivation points to defects in branches
      of the insulin signal chain and/or loss of hormonal regulation at the level of
      target enzymes.

PMID- 12217596
TI  - Thiopurine methyltransferase phenotype and genotype in relation to azathioprine
      therapy in autoimmune hepatitis.
AB  - BACKGROUND/AIMS: Toxicity and efficacy of azathioprine is governed partly by the
      activity of thiopurine methyltransferase (TPMT). Azathioprine has been used for
      many years, with corticosteroids or alone, for the treatment of autoimmune
      hepatitis (AIH) but no studies of TPMT phenotype and genotype in relation to
      response to the drug in AIH have been published. METHODS: Erythrocyte TPMT
      activities were measured by a radioincorporation assay in 72 consecutive
      outpatients with AIH, 53 of whom were genotyped for the commonest defective
      alleles in Europeans (TPMT*3A, *3B and *3C) by restriction fragment length
      polymorphism analysis. RESULTS: TPMT activities were significantly lower in
      patients intolerant of azathioprine (group I, n=15) than in those who sustained
      remission on azathioprine alone (group II, n=28; P=0.003) and those who tolerated
      azathioprine but continued to require corticosteroids (group III, n=29;
      P<0.0001), and were higher in group III than in group II (P=0.034). Ten patients
      with defective alleles (all heterozygotes) had significantly lower TPMT
      activities (P=0.002). However, in 25% there was discordance between phenotype
      and/or genotype and response to azathioprine. CONCLUSIONS: TPMT phenotyping or
      genotyping may be advisable before institution of azathioprine therapy in AIH but
      neither approach invariably predicts response to the drug.

PMID- 12217597
TI  - Combination of steroids with infliximab or placebo in severe alcoholic hepatitis:
      a randomized controlled pilot study.
AB  - BACKGROUND/AIMS: The aim of this study is to evaluate the tolerance and effects
      of infliximab combined with steroids in severe alcoholic hepatitis (AH). METHODS:
      Twenty patients with biopsy-proven severe AH (Maddrey's score>32) received
      prednisone 40 mg/day for 28 days and either infliximab 5mg/kg IV (group A) or
      placebo (group B) at day 0. Histology, plasma interleukin-6 (IL-6) and
      interleukin-8 (IL-8) were measured at baseline and at day 10. RESULTS: Infliximab
      was well tolerated. Histology showed no significant changes. At day 28, Maddrey's
      score significantly improved in group A (39 (32-53) to 12 (7-52), P<0.05 vs.
      baseline) but not in group B (44 (33-50) to 22 (2-59), P=NS). At day 10, IL-6 and
      IL-8 decreased in group A (25 pg/ml (10-85 pg/ml) to 4.5 pg/ml (2-25 pg/ml); 301
      pg/ml (107-1207 pg/ml) to 14 6 pg/ml (25-252 pg/ml), P<0.01, P<0.05 vs. baseline,
      respectively). In group B, changes were not significant (38 pg/ml (13-116 pg/ml)
      to 16 pg/ml (4-128); 315 pg/ml (26-1698 pg/ml) to 110 pg/ml (27-492 pg/ml)).
      CONCLUSIONS: In severe AH, infliximab was well tolerated and associated with
      significant improvement in Maddrey's score at day 28. Although the size of this
      study does not allow comparison between groups, these promising results should
      encourage larger trials assessing the effects of this therapy on survival.

PMID- 12217598
TI  - Effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora and
      bacterial translocation in rats with experimental cirrhosis.
AB  - BACKGROUND/AIMS: Probiotics and antioxidants could be alternatives to antibiotics
      in the prevention of bacterial infections in cirrhosis. The aim of the present
      study was to determine the effect of Lactobacillus johnsonii La1 and antioxidants
      on intestinal flora, endotoxemia, and bacterial translocation in cirrhotic rats.
      METHODS: Twenty-nine Sprague-Dawley rats with cirrhosis induced by CCl(4) and
      ascites received Lactobacillus johnsonii La1 10(9)cfu/day in vehicle
      (antioxidants: vitamin C+glutamate) (n=10), vehicle alone (n=11), or water (n=8)
      by gavage. Another eight non-cirrhotic rats formed the control group. After 10
      days of treatment, a laparotomy was performed to determine microbiological study
      of ileal and cecal feces, bacterial translocation, endotoxemia, and intestinal
      malondialdehyde (MDA) levels as index of intestinal oxidative damage. RESULTS:
      Intestinal enterobacteria and enterococci, bacterial translocation (0/11 and 0/10
      vs. 5/8, P<0.01), and ileal MDA levels (P<0.01) were lower in cirrhotic rats
      treated with antioxidants alone or in combination with Lactobacillus johnsonii
      La1 compared to cirrhotic rats receiving water. Only rats treated with
      antioxidants and Lactobacillus johnsonii La1 showed a decrease in endotoxemia
      with respect to cirrhotic rats receiving water (P<0.05). CONCLUSIONS:
      Antioxidants alone or in combination with Lactobacillus johnsonii La1 can be
      useful in preventing bacterial translocation in cirrhosis.

PMID- 12217599
TI  - Bacterial infection in cirrhosis impairs coagulation by a heparin effect: a
      prospective study.
AB  - BACKGROUND: Bacterial infections have been postulated as a trigger for variceal
      bleeding in cirrhotic patients, and impair coagulation evaluated by
      thrombelastography (TEG). Endogenous heparinoids have been detected after
      variceal bleeding and during liver transplantation in some cirrhotics using
      heparinase-modified-TEG. AIM: To assess if bacterial infection is associated with
      endogenous heparinoids in cirrhotics, thus impairing coagulation. METHODS: Native
      and heparinase-modified-TEG (cleavage of heparin and heparan-sulphate) was
      performed in 60 cirrhotics (Grade A, 2; B, 30; C, 28): 30 infected [septicaemia,
      6 (culture positive); 6 (culture negative); spontaneous bacterial peritonitis,
      10; chest infection, 4; others, 4], 30 not infected, and five infected patients
      without liver diseases, comparing TEG parameters r, alpha, and ma. Eight
      cirrhotics were studied before and after infection. The diagnosis of presence and
      type of infection was based on international standard criteria. RESULTS: A
      significant heparin effect was found only in infected cirrhotics (28 of 30) with
      significant changes in r (P=0.0003), alpha (P<0.0001), and ma (P<0.0001), but in
      none of those not infected. This effect completely reversed in the eight
      evaluated after resolution of infection. There was no heparin effect in infected
      non-cirrhotics. CONCLUSIONS: A heparin effect was only found in cirrhotic
      patients with infection, further confirming that infection significantly modifies
      coagulation in cirrhotic patients.

PMID- 12217600
TI  - Von Willebrand factor in plasma and in liver tissue after partial hepatectomy in
      the rat.
AB  - BACKGROUND/AIMS: Von Willebrand factor (vWf) is found in high levels in plasma of
      patients with acute and chronic liver disease. The role of vWf in liver injury
      and repair is unknown. We studied the effect of liver mass and remodeling on
      plasma and tissue vWf after partial hepatectomy. METHODS: Rats were sacrificed
      postoperatively at intervals ranging from 60 min to 5 days, and vWf plasma levels
      were measured by enzyme-linked immunosorbent assay, using rabbit anti-human vWf,
      and by immunoperoxidase on cryosections, using rabbit anti-vWf/factor VIII.
      Northern blot hybridization was prepared with a complementary DNA specific to
      human vWf. RESULTS: vWf plasma levels increased early after sham operation and
      after 70% partial hepatectomy. The highest levels were reached at 24 h, remaining
      high for 5 days. Immunostaining showed intense staining of sinusoidal lining
      cells 4 h after partial hepatectomy, remaining so for 5 days. Non-significant
      changes in overall liver messenger RNA expression of vWf were seen over 5 days in
      sham operation and partial hepatectomy. CONCLUSIONS: After partial hepatectomy,
      plasma vWf is increased, probably due to both acute-phase reaction and decreased
      degradation. An increase in sinusoidal vWf immunostaining may suggest a role for
      this factor in tissue remodeling.

PMID- 12217601
TI  - Woodchuck hepatitis virus replication and antigen expression gradually decrease
      in preneoplastic hepatocellular lineages.
AB  - BACKGROUND/AIMS: Hepatocellular carcinomas elicited in woodchucks by the
      woodchuck hepatitis virus (WHV) emerge gradually from parenchymal areas of
      minimal structural deviation via two predominant preneoplastic hepatocellular
      lineages, composed of either glycogenotic/basophilic or amphophilic/basophilic
      cell foci. In this study we analyzed WHV replication during neoplastic
      development in both lineages. METHODS: In minimal deviation areas, preneoplastic
      hepatocellular foci, and hepatocellular neoplasms, developing in 16 WHV-carriers
      31-38 months after WHV-inoculation, the proportion of hepatocytes containing WHV
      replicative intermediates (as detected by in situ hybridization for WHV DNA) and
      immunoreactive for WHV core and surface antigens was assessed. RESULTS:
      Appearance of WHV replicative intermediates and expression of antigens were
      limited to the cytoplasm of hepatocytes and were strongly correlated (P<0.0001),
      both showing high levels in minimal deviation areas, but markedly reduced amounts
      in all types of preneoplastic hepatic focus (P<0.0001), and in hepatocellular
      adenomas. Most hepatocellular carcinomas were negative for WHV replicative
      intermediates and antigens. CONCLUSIONS: In both the glycogenotic-basophilic and
      the amphophilic-basophilic preneoplastic hepatocellular lineage, WHV replication
      and antigen expression gradually decrease early during the preneoplastic phase.
      The close correlation of these changes with metabolic aberrations characterizing
      preneoplastic hepatocellular lineages suggests that oncogenic effects mimicking
      insulin/glucagon imbalances may be responsible for the repression of hepadnaviral
      replication.

PMID- 12217602
TI  - Infection of HepG2 cells with recombinant adenovirus encoding the HCV core
      protein induces p21(WAF1) down-regulation -- effect of transforming growth factor
      beta.
AB  - BACKGROUND/AIMS: Chronic infection with hepatitis C virus leads to liver
      cirrhosis and hepatocellular carcinoma. Hepatocellular carcinoma is sometimes
      associated with p53 dysfunction and decreased p21(WAF1) expression. The p21(WAF1)
      gene is a major target of p53, and p21(WAF1) protein regulates the activities of
      cyclin/CDK complexes involved in cell cycle control and tumor formation. Because
      core protein has oncogenic properties, we investigated the expression of
      p21(WAF1) following core expression. METHODS: We analyzed by Western blot,
      Northern blot and transfection the expression of p21(WAF1) in HepG2 cell line
      under transient expression of Hepatitis C core protein by recombinant-adenoviral
      infection. RESULTS AND DISCUSSION: Infection of HepG2 with core-encoding viruses
      induced the down-regulation of p21(WAF1) expression. This effect is due to a
      decrease in the p21(WAF1) gene transcription and of the p21(WAF1) protein half
      life. These results support a role for Hepatitis C virus core protein in cell
      transformation. We also found also that the transforming growth factor beta can
      counteract the core-induced p21(WAF1) down-regulation. The antagonist effect of
      TGF beta, or of other molecules, on p21(WAF1) expression may be of particular
      interest for the treatment of HCV-positive hepatocellular carcinoma.

PMID- 12217603
TI  - p48 Overexpression enhances interferon-mediated expression and activity of double
      stranded RNA-dependent protein kinase in human hepatoma cells.
AB  - BACKGROUND/AIMS: Double-stranded RNA-dependent protein kinase (PKR) is a key
      factor involved in interferon (IFN)-induced antiviral actions. Since p48,
      together with signal transducers and activators of transcription 1 and 2 (STAT1
      and STAT2), is an indispensable mediator in IFN-alpha signaling pathways, we
      investigated the effect of p48 gene transduction on PKR expression and its
      activity in HuH-7 human hepatoma cells. METHODS: HuH-7 cells were infected or
      transfected with p48 gene expression adenoviral vector or plasmid vector,
      respectively, and incubated with or without IFN-alpha, then PKR expression and
      phosphorylation of alpha-subunit of eukaryotic protein synthesis initiation
      factor-2 (eIF2alpha) in the cells were examined. In addition, PKR activity
      inhibiting protein translation was determined by the decrease of chloramphenicol
      acetyltransferase (CAT) gene translation or alpha-fetoprotein secretion. RESULTS:
      p48 overexpression itself could not stimulate PKR expression. However, p48
      overexpression in combination with interferon-alpha treatment caused a marked
      increase in PKR expression and augmented the phosphorylation of eIF2alpha, by
      which the transfected CAT gene translation, as well as the endogenous alpha
      fetoprotein synthesis, was blocked without affecting their mRNA levels.
      CONCLUSIONS: These results suggest that p48 gene transduction may provide a
      strategy to enhance the IFN-mediated PKR expression and its activity in
      hepatocytes.

PMID- 12217604
TI  - Prognostic factors and early predictability of sustained viral response with
      peginterferon alfa-2a (40KD).
AB  - BACKGROUND/AIMS: Baseline factors and early decline in serum hepatitis C virus
      RNA are predictive of sustained virological response to interferon therapy in
      patients with chronic hepatitis C. We evaluated the prognostic value of baseline
      factors and early viral RNA among patients treated with peginterferon alfa-2a
      (40KD). METHODS: Data were pooled from three randomized trials involving 814
      patients treated with peginterferon alfa-2a (40KD) (90, 135, or 180 mirog).
      Stepwise and multiple logistic regression identified independent baseline factors
      associated with response. Receiver operating characteristic curves for both
      absolute values and log(10) decline in viral RNA at 4, 8, 12 and 24 weeks of
      therapy were created. RESULTS: Independent prognostic factors for sustained
      virological response included viral genotype non-1, low pretreatment viral load,
      age (<40 years), no cirrhosis and body weight (<85 kg). In addition, alanine
      aminotransferase quotient (>3) and histological activity index score (>10) were
      also independently prognostic. Receiver operating characteristic curves showed
      that detectable or less than 2-log(10) decline in viral RNA at week 12 predicted
      sustained virological non-response (negative predictive value is 98%) .
      CONCLUSIONS: In patients with chronic hepatitis C treated with peginterferon alfa
      2a (40KD), the decision to continue or stop treatment can be made as early as
      week 12.

PMID- 12217605
TI  - Results of an enhanced-outreach programme of hepatitis B vaccination in the
      Netherlands (1998-2000) among men who have sex with men, hard drug users, sex
      workers and heterosexual persons with multiple partners.
AB  - BACKGROUND/AIMS: The Dutch Ministry of Health funded a pilot vaccination project
      targeting groups at high risk for sex- and drug-related hepatitis B transmission.
      METHODS: In seven Municipal Health Service (MHS) areas, three-part hepatitis B
      vaccination was offered free to men who have sex with men (MSM), drug users
      (DUs), and heterosexuals with multiple partners, including sex workers (SWs).
      Four intervention areas recruited participants through care-givers and opinion
      leaders and offered vaccination at non-MHS sites. Three control areas only used
      flyers to offer vaccination at MHS during regular hours. RESULTS: Over 18 months,
      13808 persons enrolled for the first vaccination, representing 63% of the
      targeted population in the intervention areas and 23% in control areas. In
      intervention areas, only 19% of DUs enrolled, versus 4% in control areas. In both
      areas, enrollment of the targeted heterosexual population (64%) was satisfactory.
      MSM were most compliant in having the full series. Of vaccination sources,
      general practitioners (GPs) attained highest compliance (71%, odds ratio 1.82).
      CONCLUSIONS: Dutch MHS facilities can reach high-risk individuals, but DUs
      require additional outreach. Vaccine coverage was disappointing, but our
      experience will be deployed nationwide and successful strategies might be
      employed elsewhere in countries of low endemicity.

PMID- 12217606
TI  - Decrease in CD3-negative-CD8dim(+) and Vdelta2/Vgamma9 TcR+ peripheral blood
      lymphocyte counts, low perforin expression and the impairment of natural killer
      cell activity is associated with chronic hepatitis C virus infection.
AB  - BACKGROUND/AIMS: As chronic hepatitis C virus (HCV) infection is associated with
      impaired natural killer (NK) cell cytotoxicity, we examined the phenotypes and
      perforin expression of peripheral blood lymphocytes, as well as the effect of
      interferon-alpha2b (IFN-alpha2b) therapy. METHODS: Thirty-three patients had
      chronic hepatitis C, and of them 12 had been on IFN-alpha2b treatment. Eleven
      individuals had been treated earlier with IFN-alpha2b and completely cured, and
      eight were HCV carriers with persistently normal serum alanine aminotransferase.
      Three-colour flow cytometry was used to measure the percentage of CD3(+/-)CD8+,
      CD3+CD4+, gammadeltaTcR+, Vdelta2 TcR+, Vgamma9 TcR+, Vdelta1 TcR+, CD3-CD16+,
      CD3-CD56+, CD19+ and perforin-positive cells. NK cell activity was assessed by
      single cell cytotoxic and flow cytometric assay. RESULTS: Patients with chronic
      hepatitis C showed an impaired NK cytotoxicity, decreased percentage of CD3
      negative-CD8dim-positive (NK subtype) and Vgamma9/Vdelta2 TcR+ as well as
      perforin-positive T lymphocytes, compared to controls and to those who were cured
      from HCV infection. IFN-alpha2b increased NK cell cytotoxicity and the percentage
      of perforin-positive lymphocytes. CONCLUSIONS: Our findings suggest that in
      chronic HCV infection a decreased percentage of CD3(-)CD8+, Vgamma9/Vdelta2 TcR+
      and perforin-positive T cells and simultaneous decreased peripheral NK activity
      may contribute to the impaired cellular immune response and the chronicity of the
      disease.

PMID- 12217607
TI  - Multifactorial gut barrier failure in cirrhosis and bacterial translocation:
      working out the role of probiotics and antioxidants.

PMID- 12217608
TI  - Beauty is in the eye of the beholder: emerging concepts and pitfalls in hepatic
      stellate cell research.

PMID- 12217609
TI  - Liver derived pro-inflammatory cytokines may be important in producing
      intracranial hypertension in acute liver failure.
AB  - We describe a patient with paracetamol induced acute liver failure (ALF) who
      fulfilled criteria for poor prognosis and was waiting for a liver to become
      available for transplantation. Because of severe uncontrolled intracranial
      hypertension she underwent a hepatectomy that resulted in stabilization of her
      systemic and cerebral hemodynamics. She remained anhepatic for 14 h and was
      successfully bridged to liver transplantation. The removal of the liver was
      associated with a sharp and sustained reduction in the circulating pro
      inflammatory cytokine concentration suggesting that liver derived pro
      inflammatory cytokines may be important in the pathogenesis of intracranial
      hypertension in patients with ALF.

PMID- 12217610
TI  - Positive octreotide scan in a case of hepatocellular carcinoma.

PMID- 12217611
TI  - Acute liver failure caused by diffuse hepatic melanoma infiltration.

PMID- 12217616
TI  - Parkinson's disease from WHO perspective and a public health point of view.
AB  - The World Health Organisation (WHO) occupies a unique position in the area of
      health care and represents a neutral platform that can be used to bring about
      international collaboration in research. International projects carried out by
      WHO follow public health principles and are devoted to problems and diseases that
      are frequent, cause severe disability and represent a significant burden on
      communities and societies all over the world. One of such projects is the WHO
      Global Initiative on Neurology and Public Health, which aims to increase public
      and professional awareness of the prevalence, severity and costs of neurological
      disorders as well as of the possibilities for their prevention. In the context of
      this Global Initiative and in order to raise awareness of the public health
      importance of Parkinson's disease, WHO has established a WHO Working Group on
      Parkinson's disease. The recommendations produced by this Working Group have
      guided WHO's work on public health aspects of Parkinson's disease including
      epidemiology, organisation of services and treatment, education, training and
      information, and direct and indirect costs of care.

PMID- 12217617
TI  - Evidence-based medicine (EBM) applied to Parkinson's disease treatment.
AB  - This paper is a narrative review of the concept of evidence-based medicine (EBM)
      and its application in the movement disorders field. The paper has three parts:
      1. Discussion of the generic concept of EBM and of the most commonly voiced
      criticisms; explanation of how relevant are for the comprehension of EBM
      procedures the notion of implicit and explicit knowledge; discussion of the
      scientific basis of the hierarchical organization of the evidence and the recent
      challenges to it; the different robustness of data pertaining to efficacy and to
      safety. 2. Accessibility of the evidence relevant for the treatment of Parkinson
      disease. Description of the most relevant tools to bring unbiased data to the
      hands of the practicing physician; namely the product of Movement Disorders
      Cochane Review Group and the Movement Disorders Society Evidence-Based Review of
      Parkinson Disease treatments. The concept of management guidelines is presented
      along with commentaries to the potential variability of recommendations across
      the world. 3. Limitations of the clinical trials on Parkinson disease treatment
      so far available.

PMID- 12217618
TI  - Treatment of advanced stage patients with Parkinson's disease.
AB  - Most patients with Parkinson's disease (PD) receiving chronic levodopa therapy
      eventually manifest one or more motor response complications, including 'wearing
      off' phenomena and on-off phenomena. Additionally, as the disease progresses,
      motor, neurologic, and neuropsychiatric complications increase and may include
      freezing spells, falls, dementia, depression and psychosis. The management of
      patients with advanced PD presents a special clinical challenge because patients
      may experience an enhanced sensitivity to small changes in plasma levodopa levels
      and because they may suffer adverse reactions to antiparkinsonian drugs.
      Management of advanced PD is directed toward decreasing the dose of the offending
      drug while raising the dose of alternative drug with the goal of maintaining
      symptom control. In this article, the spectrum of late complications experienced
      by patients with advanced PD and their management are discussed.

PMID- 12217619
TI  - Isolation and transplantation of dopaminergic neurons and neural stem cells.
AB  - Although transplantation of mesencephalic tissue is considered a promising
      therapy for Parkinson's disease (PD), its clinical use is still restricted to a
      very few cases. A major limiting factor of this therapy is the difficulty of
      obtaining sufficient quantities of viable embryonic mesencephalic tissue. To
      overcome this limitation, techniques to produce dopaminergic (DA) neurons in
      vitro have been developed. However, these cultures are likely to contain a
      variety of unidentified cells, which must be removed before implantation.
      Specific cell-surface markers to sort DA neurons or their precursors are not
      available. We have developed an alternative strategy, by which these cells can be
      labeled with green fluorescent protein and isolated with fluorescent activated
      cell sorter. Transplantation of the sorted cells resulted in recovery of a rat
      model of the PD. This strategy should be useful for developing new therapies for
      PD.

PMID- 12217620
TI  - The natural history of sex-linked recessive dystonia parkinsonism of Panay,
      Philippines (XDP).
AB  - Sex-linked dystonia parkinsonism (XDP) was reported by Lee et al. in 1975
      occurring endemically in Panay, Philippines. It is an adult onset, sex-linked,
      predominantly male, severe, progressive movement disorder with high penetrance
      and a high frequency of generalization. The movement disorder is characterized by
      dystonic movements usually starting in the third or fourth decade, focal at the
      onset, spreading to generalization within 2-5 years. The dystonia co-exist or is
      replaced by parkinsonism usually beyond the 10th year of illness. As of June
      2001, 376 XDP cases have been registered. One hundred and fifteen cases have
      died. The prevalence of XDP in the island of Panay is 5.24 per 100,000;
      0.34/100,000 in the general population. The prevalence varies in the different
      provinces; it is highest in Capiz at 18.88/100,000, 7.46/100,000 in Aklan, 1.28
      in Iloilo and 0.83 in Antique. The 376 cases are from 188 families and 92% of
      cases have positive family history. Ninety-nine percent of the cases are males.
      The mean age of onset is 39.48 years. Duration of illness is 12.95 years. Ninety
      four percent of patients initially manifest with dystonic symptoms, while only 6%
      present with Parkinsonian traits. Among those presenting with dystonia, the
      initial presentation is in the lower extremities in 33%, craniofacial in 27%,
      cervical and shoulder in 25%, upper extremities in 14%, and trunk in 1%.
      Regardless of the site of onset, the dystonia spreads in 98% and generalizes
      within 5 years in 84%. Neuroimaging (magnetic resonance imaging, MRI) was done in
      16 patients. In the patients who have just manifested the disease usually when
      dystonia predominates and parkinsonism is absent. MRI showed minimal atrophy of
      the caudate and putamen or subtle putaminal signal abnormality. In the late
      course, where Parkinsonism predominates, severe atrophy of the caudate and
      putamen as well as marked increase in signal abnormality are seen. There are six
      autopsied cases of XDP. Neuropathology revealed marked atrophy of the caudate and
      putamen mostly in the cases with longstanding illness. The sex-linked pattern of
      inheritance has been established. Genetic studies have located the affected gene
      (DYT3) to Xq13.1. Nemeth's group has mapped the XDP gene to a <350 kb locus in
      the DXS 7117-DX 559 region. To date, no treatment has been proven consistently
      effective.

PMID- 12217621
TI  - Progressive supranuclear palsy and its relation to pacific foci of the
      parkinsonism-dementia complex and Guadeloupean parkinsonism.
AB  - Steele, Richardson and Olszweski in 1964 described a distinctive clinical and
      pathological entity they called progressive supranuclear palsy (PSP). Now on
      Guadeloupe in the Carribbean French West Indies, Caparros-Lefebvre is identifying
      many patients with similar clinical and histological features. Others have a
      clinical syndrome of atypical parkinsonism that resembles the parkinsonism
      dementia complex (PDC) of Guam and the Kii peninsula of Japan (PDC). But in those
      Pacific foci the histology is different and the abnormal tau is of Alzheimer's
      type rather than the PSP type of Guadeloupe. In both locales, neurotoxins of
      local foods are implicated in etiology. Future studies will confirm if
      Guadeloupean parkinsonism is truly a geographic focus of PSP, and if dietary
      factors account for both.

PMID- 12217622
TI  - Mechanisms of voluntary movements.
AB  - Voluntary movements constitute a mixture of drive related, motivational deep
      brain mechanisms and cortical goal representations. Some recent studies led to a
      better understanding of these aspects of voluntary motor behaviour. These data
      are discussed with reference to the pathophysiology of Parkinson's disease.

PMID- 12217623
TI  - The management of patients with early Parkinson's disease.
AB  - A major problem in the management of early Parkinson's disease is to choose the
      first medication to prescribe. This decision should rely on the level of
      available clinical evidence, largely based, at least for efficacy, on the results
      of randomised clinical trials. Safety and costs are also crucial to consider.
      Other factors like for example pathophysiological concepts, individual
      experience, marketing pressure, socio-economical environment, patients needs and
      expectations have, however, also their own influence. Levodopa is efficacious and
      cheap, but induces long-term motor complications. The early use of dopamine
      agonists is more and more frequently promoted, because large prospective L-dopa
      controlled trials demonstrated that this strategy reduces the risk of such long
      term complications. Integrating individual clinical expertise to the best
      available external clinical evidence (evidence-based medicine) is the best
      strategy in making decisions about the care of individual patients.

PMID- 12217624
TI  - Glutathione depletion and oxidative stress.
AB  - Oxidative stress is believed to contribute to the pathogenesis of Parkinson's
      disease. One of the indices of oxidative stress is the depletion of the
      antioxidant glutathione (GSH), which may occur early in the development of
      Parkinson's disease. To study the role of GSH depletion in the survival of
      dopamine neurons we treated mesencephalic cultures with the GSH synthesis
      inhibitor L-buthionine sulfoximine. Our studies have shown that the depletion of
      GSH causes a cascade of events, which ultimately may result in cell death. An
      early event following GSH depletion is a phospholipase A(2)-dependent release of
      arachidonic acid. Arachidonic acid can cause damage to the GSH-depleted cells
      through its metabolism by lipoxygenase. The generation of superoxide radicals
      during the metabolism of arachidonic acid is likely to play an important role in
      the toxic events that follow GSH depletion.

PMID- 12217625
TI  - Increased dopamine turnover after partial loss of dopaminergic neurons:
      compensation or toxicity?
AB  - 6-Hydroxydopamine (6-OHDA) has proven a valuable tool in the study of Parkinson's
      disease (PD); it has also served to emphasize the possibility that this disorder
      may result in part from the sort of oxidative stress that 6-OHDA exerts on
      dopamine neurons. In this review we comment on several lines of our research
      related to the role of oxidative stress in PD, research that has benefited
      greatly from the work of Gerald Cohen whose memory we honor at this symposium.
      First, we discuss our use of 6-OHDA to produce an animal model of PD; second, we
      comment on our studies on dopamine's neurotoxic effects; and finally, we discuss
      our finding that tyrosine hydroxylase is regulated in part by an interaction with
      alpha-synuclein. We suggest that PD is associated with an increase in dopamine
      turnover, which may not only reduce the immediate symptoms of the disease but
      also contribute to its progression.

PMID- 12217626
TI  - Functional glutaredoxin (thioltransferase) activity in rat brain and liver
      mitochondria.
AB  - Glutaredoxin (Grx) is a specific and efficient catalyst of glutathione-dependent
      deglutathionylation of protein-SS-glutathione mixed disulfides. Grx has been
      identified in brain cytosol, but the presence of activity in subcellular
      organelles has not been reported. Increases in protein glutathionylation are
      likely to occur in mitochondria during oxidative stress and it is, therefore,
      important to know if this organelle contains the enzyme activity needed to
      reverse such protein thiolation. Grx-like activity in the P1 supernatant from rat
      brain and liver was doubled in the presence of Triton-X 100 suggesting a
      releasable pool of Grx. Brain and liver homogenates were subfractionated into
      cytosolic, mitochondrial and microsomal fraction, their purity determined by
      biochemical assay and EM and assayed for Grx-like activity. The data presented
      demonstrate that mitochondria contain functional Grx-like activity.

PMID- 12217627
TI  - Degeneration of neuronal cells due to oxidative stress--microglial contribution.
AB  - Various neurodegenerative disorders including Parkinson's disease, Alzheimer's
      disease and amyotrophic lateral sclerosis have been causally linked to the
      generation of free radicals and oxidative stress. In this review, we discuss the
      implication of oxidative stress in neuronal death and point out the role of
      intracellular signaling pathways leading to activation of transcription factors
      associated with cell death and repair. In particular, the impact of microglia as
      contributors in promoting oxidative stress in neurodegeneration is highlighted.
      Finally, pivotal molecular targets for drug therapies of brain disorders are
      reported.

PMID- 12217628
TI  - Selective destruction of dopaminergic neurons by low concentrations of 6-OHDA and
      MPP+: protection by acetylsalicylic acid aspirin.
AB  - We optimized a mesencephalic cell culture system to employ low concentrations of
      6-hydroxydopamine (6-OHDA) and 1-methyl-4 phenylpyridinium (MPP+), neurotoxins
      known to trigger oxidative stress in dopaminergic cells. Both 6-OHDA and MPP(+)
      at 5 micro M reproducibly reduced the survival of dopaminergic neurons by 50-70%
      (p<0.02) without affecting the survival of the non-dopaminergic neuronal
      population. We found that 1mM of the non-steroidal anti-inflammatory drug
      (NSAID), acetylsalicylic acid (ASA), significantly (p<0.05) increased the
      survival of dopaminergic neurons exposed to either neurotoxin. The mechanisms
      underlying neuroprotection by ASA may be of therapeutic import in Parkinson's
      disease.

PMID- 12217629
TI  - The role of dopamine in cerebral ischemic damage: a review of studies with Gerald
      Cohen.

PMID- 12217630
TI  - Alkaloids, alcohol and Parkinson's disease.
AB  - Relatively early seminal investigations on 'mammalian alkaloid biosynthesis'
      endogenous Pictet-Spengler condensations of catecholamines or indoleamines with
      aldehydes (such as acetaldehyde from ethanol metabolism) to form
      tetrahydroisoquinoline or beta-carboline alkaloids-and the roles of mammalian
      alkaloids in the CNS complications of chronic alcoholism were launched in Gerald
      Cohen's laboratory. While occasional studies on alcohol and the alkaloids
      continue today, the field of study has been expanded principally by others into
      Parkinson's disease. Certain mammalian or xenobiotic alkaloids have been examined
      by various laboratories as possible neurotoxic factors inducing mitochondrial
      energy depletion and/or oxidative stress in the nigrostriatum. In that regard,
      specific arguments for N-methylated 'MPP(+)-like' cationic alkaloids that can be
      generated centrally from beta-carbolines derived from the environment and diet
      are summarized.

PMID- 12217631
TI  - Contributions of human brain biochemical studies to movement disorders.

PMID- 12217632
TI  - Cellular effects of dopamine--beyond oxidative mechanisms.
AB  - Cell cycle blockers inhibit growth in dividing cells, but promote survival of
      differentiated cells, including neurons. Low micromolar dopamine profoundly
      inhibited cell growth in dopamine transporter transfected SK-N-MC neuroblastoma
      cells by cell cycle arrest at G(1). This effect was independent of oxy radical
      formation, antagonized by transporter block, abolished by FeCl(3) and mimicked by
      the iron chelator deferoxamine. We propose that dopamine inhibits cell growth by
      its ability to chelate intracellular iron. This novel biological action unrelated
      to neurotransmitter receptors, second messengers or oxidative stress, observed in
      human neuroblastoma cells of striatal origin, may be important for cell
      differentiation during neurodevelopment and survival of differentiated dopamine
      (nigral) neurons.

PMID- 12217633
TI  - The role of anatomical pathology in understanding human movement disorders.

PMID- 12217634
TI  - Levodopa response motor complications--GABA receptors and preproenkephalin
      expression in human brain.
AB  - Post-mortem studies in human brain of patients with Parkinson's disease have
      greatly contributed to our understanding of the disease. However, few human brain
      studies have focused on levodopa-induced dyskinesias, which considerably limit
      the beneficial effect of levodopa (LD) in the treatment of Parkinson's disease.
      We have taken advantage of the fact that some patients develop dyskinesias and
      other do not to compare biochemical markers between them. In post-mortem samples
      from LD-treated parkinsonian patients, increased preproenkephalin expression in
      the putamen and increased GABA(A) receptors content in the internal globus
      pallidus (GPi) are found in dyskinetic parkinsonian patients compared to non
      dyskinetic patients. These data are consistent with previous observations in MPTP
      monkeys developing dyskinesias following LD or dopamine agonist treatment. This
      combination of data in an animal model and in humans strongly suggests that
      increased enkephalinergic activity in the putamen and increased sensitivity of
      GABA(A) receptors in the GPi are implicated in the pathogenesis of LD-induced
      dyskinesias in Parkinson's disease.

PMID- 12217635
TI  - Physiologic studies in the human brain in movement disorders.
AB  - Physiologic studies are useful in identifying brain targets during functional
      neurosurgical procedures for the treatment of Parkinson's disease and other
      movement disorders. These studies also open a window into the function and
      dysfunction in the basal ganglia. Recording of the activity of single neurons in
      the motor thalamus, the globus pallidus or the subthalamic nucleus with
      microelectrodes is providing important insights into the pathophysiology of
      parkinsonism and the mechanism of action of medical therapy and surgical
      interventions.

PMID- 12217636
TI  - Parkinson's genetics--creating exciting new insights.
AB  - Parkinson's disease is a complex disorder in which the genetic aspects are only
      just being realized. The underlying cause for the degeneration of dopaminergic
      substantia nigra neurons and the formation of Lewy bodies in Parkinson's disease
      is unknown. The identification of clear inherited forms of the disease has
      provided important clues as to how this complex process may be occurring.
      Mutations have now been identified in the alpha-synuclein (4q21.3-23), parkin
      (6q25.2-27), and ubiquitin carboxy terminal hydrolase-L1 (4p16.3) genes in
      families with Parkinson's disease. Four additional chromosomal locations; 2p13,
      4p14-15, 1p35-36, and 12p11.2-q13.1 have been linked to Parkinson's disease
      families but no pathologic gene mutations have been identified to date. As
      additional Parkinson's disease loci are mapped and their genes identified we will
      continue to add to our understating of the critical biochemical pathways involved
      and be able to develop effective disease altering treatments.

PMID- 12217637
TI  - Transcriptional activation of estrogen receptor ERalpha and ERbeta by polycyclic
      musks is cell type dependent.
AB  - In the past decade the list of chemicals in the environment that are able to
      mimic the natural hormone estrogen, thereby disrupting endocrine function, has
      grown rapidly. These chemicals are able to bind to estrogen receptors (ERs) and
      influence estrogen signaling pathways, although several of them have structures
      that differ substantially from the endogenous hormone 17beta-estradiol. Because
      of their polycyclic nature, the polycyclic musks AHTN (6-acetyl-1,1,2,4,4,7
      hexamethyltetraline) and HHCB (1,2,4,6,7,8-hexahydro-4,6,6,7,8,8
      hexamethylcyclopenta-gamma-2-benzopyran) were assessed for interaction with
      estrogen receptors. These compounds are ubiquitously present in surface waters
      and have been identified in human milk fat and blood. Using sensitive in vitro
      reporter gene assays, we found that AHTN and HHCB act as selective estrogen
      receptor modulators (SERMs), inducing both estrogenic and antiestrogenic activity
      dependent on the cell line and the ER subtype targeted. Weak estrogenic effects
      were observed only at relatively high concentrations (10 microM). Antiestrogenic
      effects were observed in various cell lines starting at concentrations of 0.1
      microM. In comparison with the well-known SERM, 4-hydroxytamoxifen, AHTN and HHCB
      have a much lower potency in suppressing estradiol-induced transactivation.
      Results with various mutant ER receptor types suggest that binding sites of the
      musk compounds differ from 17beta-estradiol and 4-hydroxytamoxifen. The cell type
      dependency of ER transactivation shows that caution should be exerted when
      interpreting effects of estrogenic compounds using in vitro systems.

PMID- 12217638
TI  - Uterine responsiveness to estradiol and DNA methylation are altered by fetal
      exposure to diethylstilbestrol and methoxychlor in CD-1 mice: effects of low
      versus high doses.
AB  - We examined the effects on female CD-1 mice of fetal exposure to low doses of the
      drug diethylstilbestrol (DES) (0.1 microg/kg/day) and the insecticide
      methoxychlor (MXC) (10 microg/kg/day) as well as 1000-fold higher doses: 100
      microg/kg/day DES and 10,000 microg/kg/day MXC. Pregnant females were
      administered these chemicals on gestation days 12-18. At 7-8 months of age,
      female offspring were ovariectomized and implanted for 7 days with a Silastic
      capsule containing estradiol. Relative to controls, females exposed to the 0.1
      microg DES dose showed significantly heavier uteri, while females exposed to the
      100 microg DES dose showed significantly lighter uteri. Females exposed
      prenatally to the 10 microg/kg dose of MXC had significantly heavier uteri
      relative to females exposed to the 10,000 microg/kg dose of MXC, but neither
      group differed significantly from controls. Liver weight for females exposed to
      both doses of DES was significantly greater than controls. Using a microarray
      approach to analyze DNA methylation, an increase in ribosomal DNA (rDNA)
      methylation was observed. Sequence data and Southern analysis indicate an
      increase in 18S rDNA and 45S pre-rDNA methylation in uterine samples exposed
      prenatally to low and high doses of DES. We thus found opposite effects of fetal
      exposure to a low and a high dose of DES on the uterine response to estradiol
      (inverted-U dose-response relationship). In contrast, there was a monotonic dose
      response relationship found for prenatal DES exposure on both liver weight and
      ribosomal DNA hypermethylation.

PMID- 12217639
TI  - Use of a hybrid computational fluid dynamics and physiologically based inhalation
      model for interspecies dosimetry comparisons of ester vapors.
AB  - Numerous inhalation studies have demonstrated that exposure to high
      concentrations of a wide range of volatile acids and esters results in
      cytotoxicity to the nasal olfactory epithelium. Previously, a hybrid
      computational fluid dynamics (CFD) and physiologically based pharmacokinetic
      (PBPK) dosimetry model was constructed to estimate the regional tissue dose of
      organic acids in the rodent and human nasal cavity. This study extends this
      methodology to a representative volatile organic ester, ethyl acrylate (EA). An
      in vitro exposure of explants of rat olfactory epithelium to EA with and without
      an esterase inhibitor demonstrated that the organic acid, acrylic acid, released
      by nasal esterases is primarily responsible for the olfactory cytotoxicity.
      Estimates of the steady-state concentration of acrylic acid in olfactory tissue
      were made for the rat nasal cavity by using data from a series of short-term in
      vivo studies and from the results of CFD-PBPK computer modeling. Appropriate
      parameterization of the CFD-PBPK model for the human nasal cavity and to
      accommodate human systemic anatomy, metabolism, and physiology allowed
      interspecies dose comparisons. The CFD-PBPK model simulations indicate that the
      olfactory epithelium of the human nasal cavity is exposed to at least 18-fold
      lower tissue concentrations of acid released from EA than the olfactory
      epithelium of the rat nasal cavity under the same exposure conditions. The
      magnitude of this difference varies with the specific exposure scenario that is
      simulated and with the specific dataset of human esterase activity used for the
      simulations. The increased olfactory tissue dose in rats relative to humans may
      be attributed to both the vulnerable location of the rodent olfactory tissue
      (comprising greater than 50% of the nasal cavity) and the high concentration of
      rat olfactory esterase activity (comparable to liver esterase activity) relative
      to human olfactory tissue. These studies suggest that the human olfactory
      epithelium is protected from vapors of organic esters significantly better than
      rat olfactory epithelium due to substantive differences in nasal anatomy, nasal
      and systemic metabolism, systemic physiology, and air flow. Although the
      accumulation of acrylic acid in the nasal tissues may be a primary concern for
      nasal irritation and human risk assessment, acute animal inhalation studies to
      evaluate lethality (LD50-type studies) conducted at very high vapor
      concentrations of ethyl acrylate indicated that a different mechanism is
      primarily responsible for mortality. The rodent studies demonstrated that
      systemic tissue nonprotein sulfhydryl depletion is a primary cause of death at
      exposure concentrations more than two orders of magnitude above the
      concentrations that induce nasal irritation. The CFD-PBPK model adequately
      simulated the severe depletion of glutathione in systemic tissues (e.g., liver
      and lung) associated with acute inhalation exposures in the 500-1000 ppm range.
      These results indicate that the CFD-PBPK model can simulate both the low-dose
      nasal tissue dosimetry associated with irritation and the high-dose systemic
      tissue dosimetry associated with mortality. In addition, the comparison of
      simulation results for ethyl acetate and acetone to nasal deposition data
      suggests that the CFD-PBPK model has general utility as a tool for dosimetry
      estimates for a wide range of other esters and slowly metabolized vapors.

PMID- 12217640
TI  - Antiangiogenic effect of a highly selective cyclooxygenase-2 inhibitor on gastric
      ulcer healing in rats.
AB  - Selective cyclooxygenase-2 (COX-2) inhibitors have been shown to produce fewer
      gastrointestinal adverse reactions when compared with conventional nonselective
      nonsteroidal anti-inflammatory drugs and they suppress angiogenesis in tumors.
      The purpose of the present study was to investigate the effects of highly
      selective COX-2 inhibitor on angiogenesis and protein expression of angiogenic
      factor during gastric ulcer healing. Gastric ulcers were induced in male Sprague
      Dawley rats by a luminal application of acetic acid solution. Rofecoxib, a
      selective COX-2 inhibitor, was administered at a dose of 10 mg/kg/day by gastric
      intubation for 14 successive days. The ulcer size was measured at different time
      intervals after ulcer induction. The microvessels that were immunohistologically
      positive for von Willebrand factor within the ulcer bed were counted. The protein
      levels of basic fibroblast growth factor (bFGF) and concentration of
      prostaglandin E(2) (PGE(2)) in the ulcer tissues were analyzed with Western
      blotting and immunoassay methods, respectively. The results demonstrated that
      rofecoxib treatment significantly increased the ulcer size at days 6, 10, and 15.
      It decreased the number of microvessels, bFGF protein expression, and PGE(2)
      level in the ulcer base at day 6. The findings that highly selective COX-2
      inhibitor delayed ulcer healing in rats and impaired angiogenesis in the ulcer
      base raise cautions regarding the use of COX-2 inhibitors in patients with
      gastric ulcers.

PMID- 12217641
TI  - Kinetics of lung macrophages monitored in vivo following particulate challenge in
      rabbits.
AB  - The ligand PK11195 binds specifically in macrophages. We have assessed the use of
      positron emission tomography (PET) of [(11)C]R-PK11195 to monitor macrophage
      disposition following particulate challenge to the lung. Repeated PET scanning
      was performed over 4 weeks following iv [(11)C]R-PK11195 in rabbits treated with
      5-microm particles of either amorphous (aSiO(2)) or microcrystalline (xSiO(2))
      silica instilled into right upper pulmonary lobes. aSiO(2) resulted in increased
      macrophages, few neutrophils, and no fibrosis, while xSiO(2) increased
      macrophages and neutrophils and caused fibrosis. After both stimuli, (11)C
      localized to the challenged area and correlated with macrophage numbers.
      Radioactive counts in challenged/control lung regions peaked at 4 days for
      aSiO(2) (2.88, n = 2) and 6 days for xSiO(2) (4.62, n = 2). The signal remained
      elevated throughout the study (aSiO(2), 2.33 +/- 0.77 SD, n = 14; xSiO(2), 3.99
      +/- 1.29 SD, n = 9), as did macrophage accumulation. (11)C also localized to
      regions consistent with macrophage traffic through lymph ducts 6 days after
      aSiO(2) challenge, but not until 4 weeks after xSiO(2). Specific binding of R
      PK11195 in macrophages was demonstrated by microautoradiography in lavage fluid
      from an inflamed rabbit knee-joint model. These data suggest that PET scanning
      after [(11)C]PK11195 provides a new noninvasive approach for the study of
      macrophage kinetics in the lung.

PMID- 12217642
TI  - Amino acid and protein targets of 1,2-diacetylbenzene, a potent aromatic gamma
      diketone that induces proximal neurofilamentous axonopathy.
AB  - The gamma-diketone analogs 1,2-diacetylbenzene (1,2-DAB) and 2,5-hexanedione (2,5
      HD), but not the delta-diketone 1,3-diacetylbenzene (1,3-DAB) or the beta
      diketone 2,4-hexanedione, induce neuropathological changes in the rodent central
      and peripheral nervous systems. The molecular targets of these neurotoxic
      aromatic and aliphatic gamma-diketones, and of their nonneurotoxic structural
      analogs and ninhydrin, are examined by assessing their differential reactivity
      with neural and nonneural amino acids and proteins in vitro and in vivo. Whereas
      1,2-DAB is chromogenic and forms polymers with amino acids (notably lysine) and
      proteins (especially lysine-rich proteins), 1,3-DAB lacks these properties.
      Ninhydrin forms a chromophore without evidence of protein polymerization. 1,2-DAB
      preferentially targets neurofilament over microtubule protein in vitro and in
      situ. Based on protein reactivity, 1,2-DAB is three orders of magnitude more
      reactive than 2,5-HD. Lysine-rich neurofilament protein subunits NF-H and NF-M
      are more susceptible than lysine-poor NF-L and beta-tubulin to 1,2-DAB. These
      observations correlate with the development of proximal (1,2-DAB) and distal (2,5
      HD) neurofilament-filled axonal swellings and segregated intact microtubules
      observed during systemic treatment with aromatic and aliphatic gamma-diketones.

PMID- 12217643
TI  - Insights into the quantitative relationship between sensitization and challenge
      for allergic contact dermatitis reactions.
AB  - The ability of chemical or pharmaceutical agents to induce allergic contact
      dermatitis (ACD) is of major health and regulatory concern. As such, tests to
      identify their sensitizing capacity, such as the guinea pig maximization test and
      the more recently developed local lymph node assay, are broadly used. Ideally,
      for risk assessment it is useful to translate results from animal data into
      establishing safe or no-effect levels for occupational or environmental agents.
      This, of course, would require consideration of the quantitative relationships
      between sensitizing and challenge doses as well as other exposure conditions. In
      the present studies, we modeled two sensitizers, 2,4-dinitrochlorobenzene and
      squaric acid dibutyl ester, over a large range of concentrations using the LLNA
      and more traditional tests that measure both sensitization and elicitation
      responses. Both the sensitization and challenge phases provided similar dose
      response curves, demonstrating a threshold followed by a shallow linear increase
      and eventual plateau at increasing doses. Extending earlier studies by P. S.
      Friedmann (1994, Immunotoxicology and Immunopharmacology, pp. 589-616, Raven
      Press, New York) in humans, we observed that the minimum dose required to elicit
      sensitization or challenge was not static, but rather reflected a "sliding
      scale." That is, as the sensitization dose was increased, the concentration
      required to elicit a challenge response was decreased. Correspondingly, as the
      challenge dose was increased, the dose required for sensitization was lessened.
      Taken together, these findings indicate that there is a need to consider dose
      response relationships for sensitization and challenge in establishing minimum
      exposure levels for chemicals that cause ACD.

PMID- 12217644
TI  - Modulation of gene and protein expression by carbon tetrachloride in the rat
      liver.
AB  - The gene and protein expression changes after exposure to a toxic compound might
      help elucidate its mechanism of action. In this paper we investigated the effect
      of carbon tetrachloride (CCl(4)) on the gene and protein expression in rat
      livers. Adult Wistar rats were administered CCl(4) and livers were harvested 6 or
      24 h thereafter. The analysis of mitochondrial proteins on 2D gels showed the
      upregulation of two proteins involved in stress (catalase and uricase). Among the
      downregulated proteins, enzymes related to the metabolism of lipids and
      aminoacids were affected. Additionally, alpha-2-macroglobulin and senescence
      marker protein, two proteins whose decrease in expression has been connected to
      hepatocyte damage, were decreased. Several of the upregulated genes are involved
      in stress response, DNA and protein damage, and repair. Genes coding for several
      enzymes involved in different metabolic pathways, including some P450, were
      downregulated in the treated animals. In conclusion, a single dose of CCl(4)
      caused gene and protein expression changes that can be related to its mechanism
      of toxicity. Results from both technologies support previous publications and
      provide possible new toxicity markers. However, the correlation between gene and
      protein expression at a given time point is less apparent, partly as a result of
      different regulatory mechanisms between gene and protein expression.

PMID- 12217645
TI  - Heterodimerization of gamma-aminobutyric acid B receptor subunits as revealed by
      the yeast two-hybrid system.
AB  - Several lines of evidence suggested that the first gamma-aminobutyric acid B
      receptor to be cloned required an additional factor for functional expression.
      GABA(B1) was retained within the endoplasmic reticulum and failed to couple to
      signal transduction pathways on stimulation with agonists. In radioligand binding
      experiments it was found that although the affinity of antagonists showed a close
      agreement between rat brain membranes and membranes expressing the cloned
      receptor, agonist ligands were significantly weaker at recombinant receptors.
      Using the C-terminal tail as bait, a yeast two-hybrid screen was run against a
      human brain cDNA library and identified a second receptor, GABA(B2), as a major
      interacting protein. This interaction was confirmed by coimmunoprecipitation as
      well as extensive colocalization studies. Coexpression of the two seven
      transmembrane proteins generated a fully functional receptor, which was expressed
      at the cell surface confirming the importance of receptor heterodimerization for
      GABA(B) receptor activity.

PMID- 12217646
TI  - Assembly-dependent trafficking assays in the detection of receptor-receptor
      interactions.
AB  - Assembly-dependent trafficking is a property of many multimeric membrane protein
      complexes; this coupling of assembly and trafficking processes provides an
      important cellular quality control mechanism, ensuring that only properly folded
      and assembled complexes are expressed on the cell surface. In all membrane
      protein complexes whose trafficking is known to be assembly-dependent, at least
      one of the subunits contains an endoplasmic reticulum (ER) retention/retrieval
      signal that is shielded on subunit assembly, allowing the assembled protein
      complex to traffic to the plasma membrane. Under these conditions, presence of
      the normally retained subunit on the cell surface can be used as an indirect
      index of protein assembly in the ER. In this article, I describe the design of
      two complementary approaches (trafficking enhancement and trap assays) that can
      be used separately or in combination to determine whether two (or more) proteins
      assemble in the ER, i.e., whether they constitutively oligomerize. Both of the
      approaches are based on the measurement of plasma membrane-expressed proteins
      using antibody-mediated detection of extracellularly expressed epitopes and
      subsequent luminometric quantification. These methods provide a straightforward
      and relatively inexpensive way to assess protein-protein interactions early in
      the synthetic pathway.

PMID- 12217647
TI  - Use of defined-function mutants to access receptor-receptor interactions.
AB  - This article describes a novel method to access functional interactions of two
      defective mutant receptors. As a model, luteinizing hormone receptor, a G-protein
      coupled receptor, was used by coexpressing two different mutants, one defective
      in hormone binding and the other defective in signal generation. When these two
      mutants were coexpressed in a cell, the cell responded to the hormone and induced
      the hormone action, indicating the interaction of the two receptors and rescue of
      the activity. The luteinizing hormone receptor consists of a 350-amino-acid
      extracellular N-terminal domain (exodomain), followed by seven transmembrane
      domains and connecting loops (endodomain). Hormone binds to the exodomain,
      whereas hormone signals are generated in the endodomain. Here, we show that
      binding of hormone to one receptor can activate adenylyl cyclase through its
      transmembrane bundle, intramolecular activation (cis-activation), as well as
      intermolecular activation (trans-activation) through the transmembrane bundle of
      an adjacent receptor, without forming a stable receptor dimer. Our observations
      provide new insights into the mechanism of receptor activation mechanisms, and
      have implications for the treatment of inherited disorders of glycoprotein
      hormone receptors.

PMID- 12217648
TI  - Use of fluorescence resonance energy transfer to analyze oligomerization of G
      protein-coupled receptors expressed in yeast.
AB  - Oligomerization or dimerization of G-protein-coupled receptors (GPCRs) has
      emerged as an important theme in signal transduction. This concept has recently
      gained widespread interest due to the application of direct and noninvasive
      biophysical techniques such as fluorescence resonance energy transfer (FRET),
      which have shown unequivocally that several types of GPCR can form dimers or
      oligomers in living cells. Current challenges are to determine which GPCRs can
      self-associate and/or interact with other GPCRs, to define the molecular
      principles that govern these specific interactions, and to establish which
      aspects of GPCR function require oligomerization. Although these questions
      ultimately must be addressed by using GPCRs expressed endogenously in their
      native cell types, analysis of GPCR oligomerization in heterologous expression
      systems will be useful to survey which GPCRs can interact, to conduct structure
      function studies, and to identify peptides or small molecules that disrupt GPCR
      oligomerization and function. Here, we describe methods employing scanning
      fluorometry to detect FRET between GPCRs tagged with enhanced cyan and yellow
      fluorescent proteins (CFP and YFP) in living yeast cells. This approach provides
      a powerful means to analyze oligomerization of a variety of GPCRs that can be
      expressed in yeast, such as adrenergic, adenosine, C5a, muscarinic acetylcholine,
      vasopressin, opioid, and somatostatin receptors.

PMID- 12217649
TI  - Measurement of changes in fluorescence resonance energy transfer between
      gonadotropin-releasing hormone receptors in response to agonists.
AB  - Oligomerization of membrane-bound G-protein-coupled receptors has recently
      emerged as an important step in cellular signaling. Fluorescence resonance energy
      transfer (FRET) has undergone a revival as the method of choice for demonstrating
      in vivo protein-protein interactions and receptor dimerization. We have used
      chimeras of gonadotropin-releasing harmone (GnRH) receptors and various
      fluorescent proteins to investigate receptor dimerization in relation to receptor
      activation. Two pairs of FRET-compatible fluorescent proteins were used: sapphire
      with topaz, and enhanced green fluorescent protein (eGFP) with dsRed. Changes in
      the ratio between acceptor and donor fluorescence were measured after addition of
      buserelin, a GnRH agonist, and antide, a GnRH antagonist. For both pairs of
      fluorescent proteins, an increase in the ratio of acceptor to donor intensities
      was observed immediately after addition of buserelin as would be predicted if
      FRET occurred due to the microaggregation of receptors conjugated with different
      fluorescent proteins. No change in FRET was observed in time for cells in medium
      or after addition of antide. The increase in FRET signal was not uniform
      throughout a cell.

PMID- 12217650
TI  - Photobleaching fluorescence resonance energy transfer reveals ligand-induced
      oligomer formation of human somatostatin receptor subtypes.
AB  - The existence of dimers and higher oligomers of G-protein-coupled receptors
      (GPCRs) has been frequently reported using strategies based on
      coimmunoprecipitation or Western blot assays. These methods rely on highly
      artificial systems with overexpressed receptors, resulting in conflicting
      observations on the question of whether GPCR dimers are preformed or are formed
      in response to agonist treatment. Fluorescence resonance energy transfer (FRET)
      microscopy is a superior and less perturbing technique which can be performed on
      selected cell regions, e.g., plasma membrane of intact cells with a sensitivity
      high enough to allow study under physiological levels of receptor expression.
      Here we describe the application of photobleaching (pb) FRET microscopy for
      investigating ligand-dependent oligomerization of somatostatin receptors.
      Procedures for the introduction of suitable donor-acceptor fluorophores in a
      given GPCR are described. The competitive nature of FRET and photobleaching is
      exploited to enable the indirect measurement of FRET via its effect on donor
      photobleaching lifetimes on a pixel-by-pixel basis. The method allows enhanced
      resolution between 10 and 100A and represents a sensitive and specific
      biophysical tool for characterizing the assembly and regulation of GPCR oligomers
      on the cell surface.

PMID- 12217651
TI  - Analysis of G-protein-coupled receptor dimerization following chemokine
      signaling.
AB  - An abundance of information has been generated in recent decades on the signaling
      events triggered through G-protein-coupled receptors (GPCRs). Nonetheless, the
      structural changes at the cell surface that provoke receptor activation are only
      now beginning to be understood. It is becoming clear that receptors are not
      isolated entities that are activated following ligand binding, but that they
      interact with other molecules already present or recruited to the vicinity, which
      results in a wide variety of new signaling possibilities. Understanding receptor
      interactions with relatives and/or friends on the cell surface is thus critical.
      The most important point is to determine which of these interactions are "casual"
      and which give rise to functional consequences.

PMID- 12217652
TI  - Oligomerization of opioid receptors.
AB  - Opioid receptors belong to the family of G-protein-coupled receptors
      characterized by their seven transmembrane domains. The activation of these
      receptors by agonists such as morphine and endogenous opioid peptides leads to
      the activation of inhibitory G-proteins followed by a decrease in the levels of
      intracellular cAMP. Opioid receptor activation is also associated with the
      opening of K(+) channels and the inhibition of Ca(2+) channels. A number of
      investigations, prior to the development of opioid receptor cDNAs, suggested that
      opioid receptor types interacted with each other. Early pharmacological studies
      provided evidence for the probable interaction between opioid receptors. More
      recent studies using receptor selective antagonists, antisense oligonucleotides,
      or animals lacking opioid receptors further suggested that interactions between
      opioid receptor types could modulate their activity. We examined opioid receptor
      interactions using biochemical, biophysical, and pharmacological techniques. We
      used differential epitope tagging and selective immunoisolation of receptor
      complexes to demonstrate homotypic and heterotypic interactions between opioid
      receptor types. We also used the proximity-based bioluminescence resonance energy
      transfer assay to explore opioid receptor-receptor interactions in living cells.
      In this article we describe the biochemical and biophysical methods involved in
      the detection of receptor dimers. We also address some of the concerns and
      suggest precautions to be taken in studies examining receptor-receptor
      interactions.

PMID- 12217653
TI  - Monitoring receptor-mediated activation of heterotrimeric G-proteins by
      fluorescence resonance energy transfer.
AB  - Green fluorescent protein (GFP)-centered fluorescence resonance energy transfer
      (FRET) relies on a distance-dependent transfer of energy from a donor fluorophore
      to an acceptor fluorophore and can be used to examine protein interactions in
      living cells. Here we describe a method to monitor the association and
      disassociation of heterotrimeric GTP-binding (G-proteins) from one another before
      and after stimulation of coupled receptors in living Dictyostelium discoideum
      cells. The Galpha(2)and Gbetagamma proteins were tagged with cyan and yellow
      fluorescent proteins and used to observe the state of the G-protein heterotrimer.
      Data from emission spectra were used to detect the FRET fluorescence and to
      determine kinetics and dose-response curves of bound ligand and analogs.
      Extending G-protein FRET to mammalian G-proteins should enable direct in situ
      mechanistic studies and applications such as drug screening and identifying
      ligands of new G-protein-coupled receptors.

PMID- 12217654
TI  - Measuring diffusion in cell membranes by fluorescence correlation spectroscopy.
AB  - Fluorescence Correlation Spectroscopy (FCS) can measure diffusion on the cell
      surface with unparalleled sensitivity. In appropriate situations, this can be the
      most sensitive and accurate method for measuring receptor interaction and
      oligomerization. Here we attempt to describe FCS in sufficient detail so that the
      reader is able to judge when there is a compelling reason to choose this
      technique, understand the basic theory behind it, construct a FCS spectrometer in
      the laboratory, and analyze the data to obtain a meaningful estimate of the
      physical parameters.

PMID- 12217655
TI  - A Bayesian method for classification of images from electron micrographs.
AB  - Particle classification is an important component of multivariate statistical
      analysis methods that has been used extensively to extract information from
      electron micrographs of single particles. Here we describe a new Bayesian Gibbs
      sampling algorithm for the classification of such images. This algorithm, which
      is applied after dimension reduction by correspondence analysis or by principal
      components analysis, dynamically learns the parameters of the multivariate
      Gaussian distributions that characterize each class. These distributions describe
      tilted ellipsoidal clusters that adaptively adjust shape to capture differences
      in the variances of factors and the correlations of factors within classes. A
      novel Bayesian procedure to objectively select factors for inclusion in the
      classification models is a component of this procedure. A comparison of this
      algorithm with hierarchical ascendant classification of simulated data sets shows
      improved classification over a broad range of signal-to-noise ratios.

PMID- 12217656
TI  - Antiferritin VL homodimer binds human spleen ferritin with high specificity.
AB  - The antiferritin variable light domain (VL) dimer binds human spleen ferritin (
      approximately 85% L subunits) but with approximately 50-fold lower affinity,
      K(a)=4 x 10(7) x M(-1), than the parent F11 antibody (K(a)=2.1 x 10(9) x M(-1)).
      The VL dimer does not recognize either rL (100% L subunits) or rH (100% H
      subunits) human ferritin, whereas the parent antibody recognizes rL-ferritin. To
      help explain the differences in ferritin binding affinities and specificities,
      the crystal structure of the VL domain (2.8A resolution) was determined by
      molecular replacement and models of the antiferritin VL-VH dimer were made on the
      basis of antilysozyme antibody D1.3. The domain interface is smaller in the VL
      dimer but a larger number of interdomain hydrogen bonds may prevent rearrangement
      on antigen binding. The antigen binding surface of the VL dimer is flatter,
      lacking a negatively charged pocket found in the VL-VH models, contributed by the
      CDR3 loop of the VH domain. Loop CDR2 (VL dimer) is located away from the antigen
      binding site, while the corresponding loop of the VH domain would be located
      within the antigen binding site. Together these differences lead to 50-fold lower
      binding affinity in the VL dimer and to more restricted specificity than is seen
      for the parent antibody.

PMID- 12217657
TI  - Post-testicular development of a novel membrane substructure within the
      equatorial segment of ram, bull, boar, and goat spermatozoa as viewed by atomic
      force microscopy.
AB  - Atomic force microscopy has been used to investigate changes in the plasma
      membrane overlying the head region of mammalian spermatozoa (bull, boar, ram,
      goat, stallion, mouse, and monkey) during post-testicular development, after
      ejaculation, and after exocytosis of the acrosomal vesicle. On ejaculated ram,
      bull, boar, and goat spermatozoa the postacrosomal plasma membrane has a more
      irregular surface than that covering the acrosome. The equatorial segment, by
      contrast, is relatively smooth except for an unusual semicircular substructure
      within it that has a coarse uneven appearance. This substructure (referred to as
      the equatorial subsegment) is situated adjacent to the boundary between the
      postacrosomal region and the equatorial segment itself and seems to be confined
      to the order Artiodactyla as it has not been observed on stallion, mouse, or
      monkey spermatozoa. The equatorial subsegment develops during epididymal
      maturation, and following induction of the acrosome reaction with Ca(2+)
      ionophore A23187, its topography changes from a finely ridged appearance to that
      resembling truncated papillae. A monoclonal antibody to the equatorial subsegment
      binds only to permeabilized spermatozoa, suggesting that the subsegment is
      related to the underlying perinuclear theca that surrounds the sperm nucleus. A
      role for the equatorial subsegment in mediating fusion with the oolemma at
      fertilization is discussed.

PMID- 12217658
TI  - Toroidal nucleoids in Escherichia coli exposed to chloramphenicol.
AB  - The DNA of growing cells of Escherichia coli occurs in one or a few lobular
      bodies known as nucleoids. Upon exposure to chloramphenicol, the nucleoids assume
      compact, rounded forms ("cm-nucleoids") that have been described as ring- or
      sphere-shaped. Multiple views of single cells or spheroplasts, however, support a
      different, curved toroid shape for cm-nucleoids. The multiple views were obtained
      either by DNA fluorescence imaging as the cells or spheroplasts reoriented in
      liquid medium or by optical sectioning using phase-contrast or fluorescence
      imaging of immobilized cells. The curved toroid shape is consistent with electron
      microscope images of thin sections of chloramphenicol-treated cells. The
      relationship of this structure to active and inactive nucleoids and to the
      smaller toroidal forms made by in vitro DNA condensation is discussed.

PMID- 12217659
TI  - Structure of a cardiotoxic phospholipase A(2) from Ophiophagus hannah with the
      "pancreatic loop".
AB  - The crystal structure of an acidic phospholipase A(2) from Ophiophagus hannah
      (king cobra) has been determined by molecular replacement at 2.6-A resolution to
      a crystallographic R factor of 20.5% (R(free)=23.3%) with reasonable
      stereochemistry. The venom enzyme contains an unusual "pancreatic loop." The
      conformation of the loop is well defined and different from those in pancreas
      PLA(2), showing its structural variability. This analysis provides the first
      structure of a PLA(2)-type cardiotoxin. The sites related to the cardiotoxic and
      myotoxic activities are explored and the oligomer observed in the crystalline
      state is described.

PMID- 12217660
TI  - Cryo-negative staining reduces electron-beam sensitivity of vitrified biological
      particles.
AB  - Beam damage is the main resolution-limiting factor when biological particles are
      observed by cryoelectron microscopy in a thin vitrified solution film.
      Furthermore, the low contrast of the specimen frequently makes observation
      difficult and limits the possibility of image processing. Cryo-negative staining,
      in which the particles are vitrified in a thin layer of concentrated ammonium
      molybdate solution, makes it possible to visualize the particles with a much
      better signal-to-noise ratio (SNR) while keeping the specimen in a good state of
      preservation. We have observed the Escherichia coli GroEL chaperonin, prepared in
      a native vitrified solution and by cryo-negative staining after electron exposure
      from 1000 to 3000e(-)/nm(2). We have compared the resulting three-dimensional
      models obtained from these different conditions and have tested their fit with
      the atomic model of the protein subunit obtained from X-ray crystallography. It
      is found that, down to 1.5-nm resolution, the particles appear to be faithfully
      represented in the cryo-negatively stained preparation, but there is an
      approximately 10-fold increase of SNR compared with the native vitrified
      preparation. Furthermore, for the same range of irradiation and down to the same
      resolution, the particles seem unaffected by beam damage, whereas the damage is
      severe in the native vitrified particles.

PMID- 12217661
TI  - In situ atomic force microscopy of partially demineralized human dentin collagen
      fibrils.
AB  - Dentin collagen fibrils were studied in situ by atomic force microscopy (AFM).
      New data on size distribution and the axial repeat distance of hydrated and
      dehydrated collagen type I fibrils are presented. Polished dentin disks from
      third molars were partially demineralized with citric acid, leaving proteins and
      the collagen matrix. At this stage collagen fibrils were not resolved by AFM, but
      after exposure to NaOCl(aq) for 100-240 s, and presumably due to the removal of
      noncollagenous proteins, individual collagen fibrils and the fibril network of
      dentin connected to the mineralized substrate were revealed. High-aspect-ratio
      silicon tips in tapping mode were used to image the soft fibril network. Hydrated
      fibrils showed three distinct groups of diameters: 100, 91, and 83 nm and a
      narrow distribution of the axial repeat distance at 67 nm. Dehydration resulted
      in a broad distribution of the fibril diameters between 75 and 105 nm and a
      division of the axial repeat distance into three groups at 67, 62, and 57 nm.
      Subfibrillar features (4 nm) were observed on hydrated and dehydrated fibrils.
      The gap depth between the thick and thin repeating segments of the fibrils varied
      from 3 to 7 nm. Phase mode revealed mineral particles on the transition from the
      gap to the overlap zone of the fibrils. This method appears to be a powerful tool
      for the analysis of fibrillar collagen structures in calcified tissues and may
      aid in understanding the differences in collagen affected by chemical treatments
      or by diseases.

PMID- 12217662
TI  - Crystallization and preliminary X-ray diffraction studies of HutP protein: an RNA
      binding protein that regulates the transcription of hut operon in Bacillus
      subtilis.
AB  - HutP is an RNA-binding protein and regulates the expression of the histidine
      utilization (hut) operon in Bacillus subtilis by binding to cis-acting regulatory
      sequences on hut mRNA. HutP and its mutant, which has increased affinity for the
      regulatory sequences, were purified and crystallized by the hanging-drop vapor
      diffusion method. The space group was P2(1)3 with unit cell dimensions
      a=b=c=95.6A for HutP and a=b=c=96.8A for the mutant. Complete data sets of 3.0-A
      resolution for wild-type HutP and of 2.70-A resolution for the mutant HutP were
      collected.

PMID- 12217663
TI  - Prospects for stem cell transplantation in multiple sclerosis.

PMID- 12217664
TI  - New directions in migraine research.

PMID- 12217665
TI  - Reduced frequency of high cholesterol levels among patients with intracerebral
      haemorrhage.
AB  - To determine whether a relationship exists between high cholesterol levels and
      intracerebral haemorrhage (ICH) a case-control study was undertaken on 331
      consecutive cases of first-episode primary ICH, verified by computed tomography,
      and 331 age- and sex-matched community controls. Using conditional logistic
      regression the adjusted odds ratio (OR) of ICH among individuals reporting a high
      cholesterol level was 0.45 [95% confidence interval (CI), 0.28-0.73]. A similar
      finding was observed when the analysis was limited to those using cholesterol
      lowering drugs (OR 0.25; 95% CI, 0.08-0.80). These data provide support for an
      inverse relationship between high cholesterol levels and ICH. When considered
      together with previous findings, in which low cholesterol levels have been
      associated with an increased risk of haemorrhagic stroke, these data provide
      evidence that this inverse relationship may extend into a higher range of
      cholesterol values.

PMID- 12217666
TI  - Symptomatic cranial fibrous dysplasias: clinico-radiological analysis in a series
      of eight operative cases with follow-up results.
AB  - Cranial fibrous dysplasias are rare and comprise less than one percent of all
      primary bone lesions. These painless progressively expanding destructive bone
      swellings produce cosmetic deformities (commonest), sino-orbital and auditive
      complications (less common), peripheral compressive cranial neuropathies
      (uncommon) and compressive central neurological manifestations (rarest). Until
      recently some of the primary dysplastic skull base lesions were either treated
      expectantly or excised incompletely. In a significant percentage of cases, these
      lesions were considered inaccessible. However, with the development of modern
      neuro-imaging (CT and MRI) and the applications of current skull base approaches,
      the more aggressive and radical surgical procedures are being undertaken, with a
      significant improvement in overall outcome. We present a series of 8 cases of
      fibrous dysplasia in the age group of 10-33 years with a mean age of 19.75 years.
      Four cases each had monostotic type and polyostotic type. All patients presented
      with mild to moderate headaches, and seven cases with some form of cosmetic
      deformity. In 4 patients there was a unilateral proptosis, while only two had
      visual deterioration. One patient had anosmia and one hearing impairment. In one
      case fibrous dysplasia was hemicranial, and in another case the disease was
      pancranial. Neuro-imaging studies have well delineated the extent of the lesions.
      In two patients with unilateral fronto-orbital fibrous dysplasia, the removal of
      dysplastic bone, autoclaving and remodeling and replacement were performed. In
      two patients of sphenoidal wing fibrous dysplasia a total excision was possible.
      In the remaining four patients, a partial excision was performed. Overall outcome
      was good. There was no mortality. One patient had recurrent post-operative
      extradural haematomas. The authors present the results of an analysis of eight
      surgically treated cases of symptomatic cranial fibrous dysplasias along with
      their long-term outcome and the lessons learnt from this series.

PMID- 12217667
TI  - The preservation and reconstruction of cerebral veins and sinuses.
AB  - Although cerebral veins and venous sinuses are very important to the
      neurosurgeon, they have received adequate attention only recently. The
      consequences of cerebral venous occlusion are well known. When the venous outflow
      is compromised due to a lack of adequate collateral circulation, venous
      infarction follows, with swelling, haemorrhage and neuronal death. The clinical
      consequences will depend upon the region of involvement of the brain and the site
      of the infarcted tissue. The symptoms may include seizures, hemiplegia, aphasia,
      coma and death. Similarly, the consequences of cerebral venous sinus occlusion
      depend upon the availability of collateral circulation. When such collaterals are
      not available, papilledema and visual loss and a pseudotumour cerebri syndrome
      are observed in milder cases, whereas, severe diffuse brain swelling, coma and
      death may be observed in severe cases. Acute venous or venous sinus occlusion is
      potentially very dangerous, whereas slow and chronic venous or venous sinus
      occlusion is better tolerated. Even in such patients, some neurological
      manifestations may follow, when the collaterals are poor.

PMID- 12217668
TI  - Role of single photon emission computed tomography and transcranial Doppler
      ultrasonography in clinical vasospasm.
AB  - This report presents our experience with Transcranial Doppler (TCD)
      ultrasonography and Single Photon Emission Computed Tomography (SPECT) in the
      assessment of patients with aneurysmal subarachnoid haemorrhage (SAH). It was
      designed to evaluate clinical vasospasm with both TCD and SPECT and determine
      their diagnostic value. Twenty-eight consecutive patients were examined with both
      TCD and SPECT, performed within 24 hours of each other. They had a total of 45
      TCDs and 46 SPECT scans. Eight patients (29%) developed clinical vasospasm, noted
      from day 2 to day 11 post subarachnoid haemorrhage; these patients underwent TCDs
      and SPECT scans when the diagnosis of vasospasm was made. Twenty patients (71%)
      did not demonstrate clinical vasospasm throughout their hospital stay and
      underwent TCDs and SPECT scans within the first 2 weeks of their SAH, mostly
      between day 2 and day 10, the period of greatest risk for vasospasm. TCD and
      SPECT sensitivity for clinical vasospasm was 100% and 50% respectively, their
      specificity was only 20% and 60%. TCD sensitivity for symptomatic vasospasm was
      found to be excellent, whereas SPECT was not found to be as useful. We conclude
      that TCD is the preferred method in the evaluation of patients with subarachnoid
      haemorrhage.

PMID- 12217669
TI  - Aggressive surgical treatment of elderly patients following subarachnoid
      haemorrhage: management outcome results.
AB  - This report presents 74 consecutive cases of subarachnoid haemorrhage (SAH) in
      patients aged 70 years or older, compared with the 317 consecutive younger
      patients treated during the same period. An ultra-early surgical strategy for all
      SAH cases was used throughout the study period. Management outcome for all grades
      of elderly patients was independent in 38%, dependent in 14% and death in 49%.
      Surgical 3-month outcome of good grade elderly patients was independent 53%,
      dependent 19% and death 28%; and for poor grades was independent 35%, dependent
      15% and death 50%. Elderly poor grade patients had similar outcome to younger
      patients, although good grade patients had better outcome in the younger group
      than the elderly group. Despite ultra-early surgery, rebleeding (<12 h of SAH)
      occurred in 9% of the elderly series. Aggressive, ultra-early treatment is likely
      to benefit elderly SAH patients, the potential benefit being greater for poor
      grade elderly patients.

PMID- 12217670
TI  - Discectomy strategies for lumbar disc herniation: results of the LAPDOG trial.
AB  - Since its introduction in the 1970s percutaneous treatment of lumbar disc
      herniation has been an attractive concept that has been the object of technical
      development and clinical application throughout the world. Little scientific
      evaluation of the efficacy and effectiveness of the procedure has been done. To
      estimate the success rates of automated percutaneous and conventional discectomy
      in comparable patients and to document the resource consumption of patients
      treated in these ways, a multicenter randomized clinical trial designed to
      compare both treatment efficacy and cost-effectiveness of automated percutaneous
      discectomy and conventional discectomy in adult patients with no prior lumbar
      spinal surgery, no coexistent lumbar spinal disease, unilateral single level
      lumbar radiculopathy with images confirming disc herniation at the appropriate
      level. In the course of the trial important technical advances allowing epidural
      extraction of free-fragment disc herniation was incorporated into the trial. It
      was not possible to enroll the required number of patients to complete the trial.
      Of 5735 screened patients, 95 were eligible and 36 were enrolled. Two elected
      watchful waiting and did not have any surgical procedure. Eight patients were
      lost to follow-up. Among the 27 evaluable patients, 41% of the percutaneous
      discectomy patients and 40% of the conventional discectomy patients were assessed
      as achieving "success" on the primary outcome measure. No clinical trial of any
      percutaneous discectomy technique provides definitive evidence supporting the
      efficacy or effectiveness of the procedure. Such evidence should be required by
      patients to whom such procedures are proposed and those who are asked to pay for
      them.

PMID- 12217671
TI  - Bypass to the intracranial internal carotid artery.
AB  - Extracranial to intracranial internal carotid artery bypass surgery with vein is
      well described for a number of diverse conditions. They provide high blood flow
      with good initial patency. However, long term patencies for specific graft types
      remains unknown. This is an analysis of consecutive interposition saphenous vein
      bypass cases between the common carotid artery (CCA) and the intracranial
      internal carotid artery (ICA) where the distal anastomosis was placed end-to-end
      immediately proximal to the posterior communicating artery in 55 patients
      undergoing 57 bypass procedures (bilateral in 2 cases). Twenty-five patients
      underwent grafting for planned vessel obliteration where the pathology required
      vessel sacrifice. Twenty-eight patients had bypass grafting for stroke risk
      reduction in the setting of threatening stroke and 4 patients had bypass grafts
      for emergency revascularisation in the setting of stroke in evolution. Patients
      were assessed preoperatively and at follow-up with modified Rankin scores.
      Procedural related complications included a 7% mortality and 7% functional
      decline. Early graft occlusion occurred in 5% of grafts leading to death in each
      case. A further patient died of rupture at the distal anastomosis site. In
      surviving patients, patency was present in 100% at last follow-up (mean 5 years
      and maximum 11 years) with no patient sustaining new hemispheric ischemic events.
      One patient developed a delayed asymptomatic stenosis within the vein graft
      requiring stenting. Because of the high initial management risks this technique
      of common carotid to intracranial internal carotid artery saphenous vein bypass
      surgery should be reserved for patients at considerable risk by alternate
      management. However, once the acute postoperative period is past the bypass
      appears to be robust and capable of supplying the entire distribution of a normal
      internal carotid artery.

PMID- 12217672
TI  - Haemoglobin and ATP levels in CSF from a dog model of vasospasm.
AB  - Haemoglobin and adenosine 5'-triposphate (ATP) released from lysed erythrocytes
      have been postulated to be responsible for delayed cerebral vasospasm after
      subarachnoid haemorrhage (SAH). However, the concentrations of haemoglobin and
      ATP in cerebrospinal fluid (CSF) in patients or in an animal model of vasospasm
      have not been reported. In this study, 12 mongrel dogs underwent a double blood
      injection via the cisterna magna on day 0 and 2, after an initial collection of
      CSF. On day 3, 5 or 7, the dogs were sacrificed after a second collection of CSF.
      An angiogram was recorded on day 0 and on the day of sacrifice. Results showed
      that the diameter of the dog's basilar artery was reduced 20% on day 3 (P >
      0.05), 35% on day 5 (P < 0.05) and 45% on day 7 (P < 0.05). The concentrations of
      OxyHb, deOxyHb and MetHb in CSF were increased (P < 0.05), and all peaked on day
      3. OxyHb and MetHb remained significantly higher than control (day 0) from day 3
      to day 7, while deOxyHb remained at a high level on day 5 but returned to normal
      on day 7. In contrast, ATP was decreased (P < 0.05) on days 5 and 7 after SAH
      compared with day 0. The results indicate that haemoglobin might be involved in
      the development of cerebral vasospasm. The possible role of ATP in vasospasm
      remains unclear.

PMID- 12217673
TI  - Resolution of cerebral vasospasm with trapidil; an animal model.
AB  - Cerebral vasospasm and rebleeding are important clinical phenomena associated
      with a high mortality rate. Therefore, any promising finding in the laboratory
      deserves assessment in clinical practice. The present study was designed to
      examine the possible effects of trapidil on the basilar artery of the rabbit
      through a cerebral vasospasm model. This experimental study was carried out on 26
      adult New Zealand albino rabbits of both sexes weighing 2.5-3.0 kg. A transclival
      exposure was performed. Vasospasm was produced by an intracisternal injection of
      autologous blood. After observation of the vasospasm, trapidil was locally
      applied in increasing concentrations (10(-5)-10(-4) M). The effect of each
      concentration was measured independently after 10 minutes for each application
      and was extended to three hours. Trapidil was shown to have a clear spasmolytic
      effect on the rabbit's basilar artery. These data suggest that trapidil can have
      a potential use in the treatment of patients suffering from cerebral vasospasm.

PMID- 12217674
TI  - Magnetic resonance imaging confirmation of resolution of periodontoid pannus
      formation following C1/C2 posterior transarticular screw fixation.
AB  - Chronic odontoid fractures are considered unstable spinal lesions. Chronic
      instability in this region leads to the development of an inflammatory pannus,
      which can progress resulting in spinal cord compression radiographically and a
      myelopathy syndrome clinically. In this report we document three cases of
      reversal of pannus after C1/C2 transarticular screw fixation of an unstable
      odontoid fracture. Three patients were identified with chronic odontoid fractures
      and spinal cord compression due to periodontoid pannus formation. All patients
      presented with a progressive myelopathy syndrome. All patients underwent
      preoperative and postoperative magnetic resonance imaging (MRI) of the
      craniovertebral junction. C1/C2 transarticular screw fixation was performed for
      stabilization of C1/C2. Postoperatively there were no complications.
      Postoperative MRI at 6 months demonstrated resolution of the ventral pannus.
      Moreover, all patients exhibited improvement of preoperative neurological
      deficits. MRI is the imaging technique of choice for diagnosis and follow-up of
      patients with chronic odontoid fractures and ventral pannus. C1/C2 transarticular
      screw fixation provides a viable method for spinal stabilization in this region.
      In addition, stabilization can result in resolution of inflammatory pannus
      formation secondary to instability of the C1/C2 articulation.

PMID- 12217675
TI  - Endoscopic assisted posterior decompression for spinal neoplasms.
AB  - The authors describe a technique for anterior thoracic decompression via a
      posterolateral approach for spinal metastatic disease followed by anterior and
      posterior column stabilization. We discuss the benefits of decompression via a
      posterolateral approach including minimization of cord retraction, avoidance of
      thoracotomy, early mobilization and shorter hospital stay. Technical details are
      reviewed and difficulties of the approach discussed.

PMID- 12217676
TI  - Discectomy strategies for lumbar disc herniation: study design and implications
      for clinical research.
AB  - Although previous studies have found automated percutaneous discectomy and
      epidural percutaneous discectomy to be less efficacious than conventional
      discectomy, these percutaneous procedures may be effective and cost-effective as
      a first surgical treatment for herniated lumbar disc. Percutaneous procedures for
      herniated lumbar disc continue to be performed throughout the world without
      definitive evidence of efficacy or effectiveness. The objective of this article
      is to report the design considerations and final design of a study with the
      following objectives: (1) to estimate the efficacy of automated percutaneous and
      conventional discectomy in treating single level herniated lumbar discs in
      comparable patient populations, and (2) to test the hypothesis that the use of
      percutaneous discectomy as the first surgical procedure in such patients would
      result in less cost and fewer complications than utilizing conventional
      discectomy as the first procedure. A multicenter randomized clinical trial was
      designed that followed published eligibility criteria closely, allowed
      flexibility in timing of surgery (while collecting natural history information on
      patients identified before electing surgery), incorporated adjustments for newly
      developed technology and accommodated the unusual demands of assessing a
      procedure acknowledged to have inferior medical outcomes when compared to
      conventional therapy but which offered potential advantages in cost and safety.
      The study was successfully designed and funded. In its implementation we
      experienced several obstacles that may affect the success of other clinical
      trials. Despite using established eligibility criteria, our patient enrollment
      was lower than expected. Academic health centers and traditional research
      settings are seeing fewer patients who would be eligible for discectomy; private
      clinical centers are treating eligible patients but lack the incentives to
      participate in clinical research. Automated percutaneous discectomy and epidural
      percutaneous discectomy are widely performed procedures and, despite the
      aforementioned obstacles, their efficacy and cost-effectiveness need to be
      scientifically evaluated if we are committed to delivering appropriate patient
      care.

PMID- 12217677
TI  - Cholesterol granuloma in the middle fossa presenting 30 years after surgery for
      chronic otitis media: a case report.
AB  - A massive left subtemporal extradural cholesterol granuloma in a 45 year old male
      patient is reported. The lesion communicated with the petrous temporal bone and
      was diagnosed after it became symptomatic 30 years following surgery for left
      chronic otitis media. The case is analysed and the literature on the subject is
      reviewed.

PMID- 12217678
TI  - Aggressive intracranial fibromatosis: case report.
AB  - Fibromatosis is a locally aggressive, proliferative fibroblastic lesion affecting
      musculoaponeurotic structures, most often in the limbs and trunk. Intracranial
      fibromatosis is extremely rare and requires aggressive treatment to prevent
      recurrence. We present the case of a 48 year old woman with aggressive skull base
      fibromatosis. The lesion extended through the sphenoid sinus, into both pterygoid
      recesses, destroying the right lateral wall of the sphenoid sinus and invading
      the cavernous sinus. There was also involvement of the floor of the sella, the
      clivus, the right petrous temporal bone and the right mastoid. The patient
      underwent partial resection of the lesion via an extended trans-sphenoidal
      approach. Postoperative MRI showed residual tissue. A review of the literature
      shows that intracranial fibromatosis usually appears in the first or second
      decade. Complete resection is often impossible because of its widely infiltrative
      nature. Radiotherapy and chemotherapy are often required to improve local control
      of the lesion.

PMID- 12217679
TI  - Multicystic acoustic neurinoma: report of two cases.
AB  - A report of two unusual and remarkably similar cases of multicystic acoustic
      neurinoma in 46 and 60 year old patients is presented. The clinical presentation
      mimicked a regular acoustic neurinoma. The tumours in each case were similar in
      their radiological appearance. The entire tumour had a honeycomb appearance with
      well defined and multiple cysts. Each cyst contained xanthochromic fluid. Like in
      any other cystic acoustic neurinoma, the presence of multiple cysts made internal
      decompression of the tumour relatively easy but the dissection of the tumour from
      the adjoining cranial nerves was difficult. The pathogenesis of multiple cysts is
      analyzed and the literature on this subject is briefly reviewed.

PMID- 12217680
TI  - Fatal cerebral infarction after intraventricular hemorrhage in a pregnant patient
      with moyamoya disease.
AB  - Moyamoya disease is a progressive occlusive cerebrovascular disorder of unknown
      etiology. We describe a case of a fatal cerebral infarction after
      intraventricular hemorrhage in a 29-year-old primipara with moyamoya disease. The
      patient had been stable for about 10 days after the initial hemorrhage, but she
      showed a fulminant clinical course of cerebral infarction, and died on the 16th
      day after the initial hemorrhage. Abnormality in coagulation system and/or
      cerebral vasospasm may have resulted in such a fulminant clinical course. A
      possible pathogenesis of this rare condition is discussed.

PMID- 12217681
TI  - Pediatric giant cell granuloma of the temporal bone: a case report and brief
      review of the literature.
AB  - Giant cell granuloma of the skull base is a distinct rare clinicopathologic
      lesion, which progressively destroys the involved bone. It causes increased
      intracranial pressure and mass effect on the brain. Histologically it may mimic
      an aneurysmal bone cyst, giant cell tumour and the brown tumour of
      hyperparathyroidism. Although cited by some authors, the role of trauma in its
      aetiology is still considered controversial. Authors present an interesting case
      of a 12 year old Omani boy who sustained a cricket bat injury to his right
      temporal region from which he initially recovered but later on progressively
      developed vertigo, tinnitus, right hearing loss and a mild right facial weakness.
      Computed tomography (CT scan) and Magnetic resonance imaging (MR scan) revealed a
      large destructive lesion of the temporal bone. Microsurgical excision was
      curative. Interesting clinicoradiological findings are presented with a brief
      review of the literature.

PMID- 12217682
TI  - Unilateral ossification of the ligamentum flavum in the cervical spine with
      atypical radiological appearance.
AB  - We report a case of symptomatic unilateral ossification of the ligamentum flavum
      with unusual radiological presentation in the cervical spine. The patient was a
      64 year old man with numbness and weakness of the left upper extremity who was
      admitted to our hospital. Computerized tomography revealed a triangular-shaped
      high density mass severely compressing the spinal cord at C6. Concomitant small
      ossification of the posterior longitudinal ligament was noted from C3 to C6. The
      ossified mass was completely removed via a unilateral osteoplastic laminectomy of
      the left C6 and C7.

PMID- 12217683
TI  - Mistaken identity: a case of false positive on CT angiography.
AB  - We describe the case of a 42-year-old female presenting with subarachnoid
      haemorrhage from a posterior inferior cerebellar artery (PICA) aneurysm rupture
      on intracranial digital subtraction angiography (DSA). One year postoperatively,
      the patient was followed with CT angiography and was reported to show a de novo
      aneurysm at the bifurcation of the left inferior cerebellar artery (ICA).
      Subsequent DSA revealed an aberrant vein crossing over the ICA bifurcation on
      mask phase images. This is the first reported case of a such a reason for a
      'false positive' on CT angiography (CTA). The case demonstrates that although CTA
      has a reported high specificity, careful interpretation of multiple views is
      required to diagnose intracranial aneurysms when compared to the 'gold' standard
      of CTA.

PMID- 12217684
TI  - Traumatic aneurysm of the callosomarginal artery.
AB  - Intracranial aneurysms are rare complications of head injury. The primary goals
      in the management of patients harbouring these lesions are early identification
      and intervention to prevent bleeding or rebleeding. The authors present a case of
      traumatic false aneurysm of the callosomarginal artery which was diagnosed
      following head injury and managed successfully with a good outcome.

PMID- 12217685
TI  - Post-traumatic intradiploic leptomeningeal fistula and cyst.
AB  - A 59 year old female patient presented with ataxia and difficulty in walking. The
      neurological examination revealed right homonymous hemianopia and ataxia.
      Radiographic evaluation revealed a large occipital intradiploic cyst mainly in
      the left suboccipital area. There was also moderate hydrocephalus and
      encephalomalacia of the left occipital pole. Bone window studies also
      demonstrated a growing fracture extending from the upper pole of the cyst to the
      vertex. Both pathologies were attributed to child abuse the patient suffered when
      she was a child. At first surgery, decompression of the cerebellum was followed
      by duroplasty and acrylic cranioplasty to the posterior cranial fossa. A month
      later, a shunt had to be inserted for hydrocephalus. At 7 months postoperatively,
      the patient is well and free of any symptoms or recurrence.

PMID- 12217686
TI  - Multiple cerebral infarcts following septic shock.
AB  - A 60-year-old female in septic shock developed neurological signs and symptoms.
      She had left-sided hemiparesis, left homonymous hemianopia, bimanual coordination
      disorder, a language dysfunction of anomic aphasic type and a non-aphasic right
      hemispheric communication disorder. Computer tomography demonstrated bilateral
      anterior and posterior watershed as well as territorial infarctions. Risk factors
      included chronic airways limitation, cardiac failure and heavy smoking. Carotid
      duplex studies were normal. The mechanisms can be explained by flow changes and
      thrombus formation.

PMID- 12217687
TI  - Wernicke's encephalopathy presenting with upbeating nystagmus.
AB  - The case of a 49-year-old woman with Wernicke's encephalopathy is described, in
      which primary position upbeating nystagmus was the chief ocular sign. Although
      there was no history of excessive alcohol consumption, Wernicke's encephalopathy
      was diagnosed on a background of anorexia nervosa. The diagnosis was supported by
      the patient's symptomatic and clinical recovery following thiamine therapy.

PMID- 12217688
TI  - A comprehensive alanine scanning mutagenesis of the Escherichia coli
      transcriptional activator SoxS: identifying amino acids important for DNA binding
      and transcription activation.
AB  - SoxS is the direct transcriptional activator of the superoxide regulon. SoxS
      recognizes a highly degenerate "soxbox" DNA sequence, and activates transcription
      from class I and class II promoters. SoxS is the smallest member of the AraC/XylS
      family of transcription regulators whose hallmark is dual helix-turn-helix (HTH)
      DNA-binding motifs. Evidence suggests that the N-terminal HTH motif of SoxS
      interacts with a highly conserved region of the soxbox termed recognition element
      1 (RE1), while the C-terminal HTH motif interacts with the less conserved
      recognition element 2 (RE2). In the work described here, we prepared a complete
      library of 101 SoxS mutants containing single alanine substitutions of SoxS, and
      we characterized the mutant proteins in vivo and in vitro. With SoxS being
      closely related to MarA, we analyzed the effects of the SoxS mutations in the
      context of the MarA-mar crystal structure and with respect to the NMR study of
      MarA-DNA complexes in solution. From the properties of the alanine substitutions,
      we conclude the following. (1) Surface-exposed residues of helix 3 and helix 6,
      the recognition helices of the dual HTH motifs, are important to DNA binding and
      transcription activation; however, substitutions of residues predicted from the
      MarA-mar crystal structure to make contact with the sugar-phosphate backbone are
      more detrimental to DNA binding than mutations predicted to make base-specific
      contacts. (2) Substitution of several residues within the recognition helix
      predicted to make base-specific contacts with RE2 have relatively little effect
      on DNA-binding, suggesting the possibility of alternative protein-DNA
      interactions than those inferred from the MarA-mar crystal structure. (3) DNA
      binding and transcription activation were reduced by substitution of conserved
      amino acid residues comprising the hydrophobic core, presumably because they
      disrupt the structural integrity of SoxS. (4) Mutant K30A appears to be a
      positive control mutant defective in a protein-protein interaction with RNA
      polymerase that is required for transcription activation at all SoxS-dependent
      promoters because it binds and bends DNA normally but fails to activate
      transcription from both classes of promoters. Alanine substitutions of surface
      exposed residues H3, K5, D9, S31, and V45 confer a similar phenotype. Since these
      residues are near K30 on the surface of the protein, the surface formed by the
      six residues may be used to make protein-protein interactions with RNA polymerase
      that are required for transcription activation at both class I and class II SoxS
      dependent promoters. (5) Mutants F74A, D75A, M78A, D79A and Q85A appear to define
      a surface required for protein-protein interaction with RNA polymerase
      specifically at class II promoters because these positive control mutants bind
      and bend DNA normally but are defective in activation of class II promoters but
      not class I promoters. These SoxS mutants that bind and bend DNA normally but are
      defective in transcription activation represent the first positive control
      mutants with putative defects in protein-protein interactions with RNA polymerase
      among the SoxS/MarA/Rob subset of the AraC/XylS family of transcription
      regulators.

PMID- 12217689
TI  - The RUNX1 Runt domain at 1.25A resolution: a structural switch and specifically
      bound chloride ions modulate DNA binding.
AB  - The evolutionarily conserved Runt homology domain is characteristic of the RUNX
      family of heterodimeric eukaryotic transcription factors, including RUNX1, RUNX2
      and RUNX3. The genes for RUNX1, also termed acute myeloid leukemia protein 1,
      AML1, and its dimerization partner core-binding factor beta, CBFbeta, are
      essential for hematopoietic development and are together the most common targets
      for gene rearrangements in acute human leukemias. Here, we describe the crystal
      structure of the uncomplexed RUNX1 Runt domain at 1.25A resolution and compare
      its conformation to previously published structures in complex with DNA, CBFbeta
      or both. We find that complex formation induces significant structural
      rearrangements in this immunoglobulin (Ig)-like DNA-binding domain. Most
      pronounced is the movement of loop L11, which changes from a closed conformation
      in the free Runt structure to an open conformation in the CBFbeta-bound and DNA
      bound forms. This transition, which we refer to as the S-switch, and accompanying
      structural movements that affect other parts of the Runt domain are crucial for
      sustained DNA binding. The closed to open transition can be induced by CBFbeta
      alone; suggesting that one role of CBFbeta is to trigger the S-switch and to
      stabilize the Runt domain in a conformation enhanced for DNA binding.A feature of
      the Runt domain hitherto unobserved in any Ig-like DNA-binding domain is the
      presence of two specifically bound chloride ions. One chloride ion is coordinated
      by amino acid residues that make direct DNA contact. In a series of
      electrophoretic mobility-shift analyses, we demonstrate a chloride ion
      concentration-dependent stimulation of the DNA-binding activity of Runt in the
      physiological range. A comparable DNA-binding stimulation was observed for
      negatively charged amino acid residues. This suggests a regulatory mechanism of
      RUNX proteins through acidic amino acid residues provided by activation domains
      during cooperative interaction with other transcription factors.

PMID- 12217690
TI  - The protein synthesis inhibitors, oxazolidinones and chloramphenicol, cause
      extensive translational inaccuracy in vivo.
AB  - The oxazolidinone family is a new class of synthetic antibiotics that bind to the
      bacterial 50S ribosomal subunit. Two members of the family, linezolid and XA043,
      were examined for their effects on translational fidelity using a lacZ reporter
      gene in vivo. Both promoted highly significant frameshifting and nonsense
      suppression. Chloramphenicol, a peptidyl transferase inhibitor, affected
      translational fidelity in a similar fashion. Neither the oxazolidinones nor
      chloramphenicol stimulated misincorporation of amino acid residues at position
      461 in the lacZ gene. In contrast, the aminoglycosides gentamicin and
      paromomycin, which interact with the decoding region of the 30S subunit, caused
      significant misincorporation but only modest increases in frameshifting or stop
      codon readthrough of the lacZ gene. We conclude that effects on translational
      fidelity may play a significant role in the mechanism of action of the
      oxazolidinones.

PMID- 12217691
TI  - Structural properties of FliH, an ATPase regulatory component of the Salmonella
      type III flagellar export apparatus.
AB  - FliH is a regulatory component for FliI, the ATPase that is responsible for
      driving flagellar protein export in Salmonella. FliH consists of 235 amino acid
      residues, has a quite elongated shape, exists as a homodimer and together with
      FliI forms a heterotrimer. Here, we have investigated the structural properties
      of the FliH homodimer in further detail. Like intact His-tagged FliH homodimer,
      fragment His-FliH(N2) (consisting of the first 102 amino acid residues of FliH),
      exhibited anomalous elution behavior in gel filtration chromatography; the same
      was true of His-FliH(C1) (consisting of amino acid residues 119-235), but to a
      much lesser degree. Thus the elongated shape of FliH appears to derive primarily
      from its N-terminal region. A deletion version of N-His-FliH, lacking amino acid
      residues 101-140, does not dimerize and so we were able to establish the gel
      filtration properties of an almost full-size monomeric form; it also exhibited
      anomalous elution behavior. We performed trypsin proteolysis of the FliH
      homodimer and subjected the cleavage products to gel filtration chromatography.
      FliH was degraded by trypsin and a contaminating protease into two stable
      fragments: FliH(Prt1) (missing both the first ten and the last 12 amino acid
      residues), and FliH(Prt2) (missing both the first ten and the last 63 amino acid
      residues); however, substantial amounts remained undigested even after 24 hours.
      Under native conditions, both FliH(Prt1) and FliH(Prt2) co-eluted with undigested
      His-FliH from the gel filtration column, indicating that the fragments exist as a
      hybrid dimer with intact FliH. These results suggest that the two subunits within
      the dimer differ in their proteolytic susceptibility. No heterotrimer was
      observed by gel filtration chromatography when His-FliI was mixed with either His
      FliH/FliH(Prt1) or His-FliH/FliH(Prt2) hybrid dimers. A hybrid dimer of FliH and
      His-FliHDelta1 (lacking the first ten amino acid residues) retained the ability
      to form a complex with His-FliI. In contrast, hybrid dimers consisting of FliH
      and either His-FliH(W223ochre) or His-FliH(V172ochre) failed to complex to His
      FliI, demonstrating that the C-terminal region of both FliH monomers within the
      FliH dimer are required for heterotrimer formation.

PMID- 12217692
TI  - Toward understanding the mutagenicity of an environmental carcinogen: structural
      insights into nucleotide incorporation preferences.
AB  - Bulky carcinogen-DNA adducts, including (+)-trans-anti-[BP]-N(2)-dG derived from
      the reaction of (+)-anti-benzo[a]pyrene diol epoxide with guanine, often block
      the progression of DNA polymerases. However, when rare bypass of the lesions does
      occur, they may be misreplicated. Experimental results have shown that
      nucleotides are inserted opposite the (+)-trans-anti-[BP]-N(2)-dG adduct by
      bacteriophage T7 DNA polymerase with the order of preference A>T>or=G>C. To gain
      structural insights into the effects of the bulky adduct on nucleotide
      incorporation within the polymerase active site, molecular modeling and molecular
      dynamics simulations were carried out using T7 DNA polymerase to permit the
      relation of function to structure. We modeled the (+)-trans-anti-[BP]-N(2)-dG
      adduct opposite incoming dGTP, dTTP and dCTP nucleotides, as well as unmodified
      guanine opposite its normal partner dCTP as a control, to compare with our
      previous simulation with dATP opposite the adduct. The modeling required that the
      (+)-trans-anti-[BP]-N(2)-dG adduct adopt the syn conformation in each case to
      avoid deranging essential protein-DNA interactions. While the dATP: (+)-trans
      anti-[BP]-N(2)-dG pair was well accommodated within the active site of T7 DNA
      polymerase, dCTP fit poorly opposite the adduct, adopting an orientation
      perpendicular to the plane of the syn modified guanine during the simulation.
      Rotation about the glycosidic bond of the dCTP residue to this abnormal position
      was allowed because only one hydrogen bond between dCTP and the (+)-trans-anti
      [BP]-N(2)-dG residue evolved during the simulation, and this hydrogen bond was
      directly across from the dCTP glycosidic bond. The dTTP and dGTP nucleotides,
      incorporated with an intermediate preference opposite (+)-trans-anti-[BP]-N(2)
      dG, were accommodated reasonably well, but not as stably as the dATP nucleotide,
      due to a skewed primer-template alignment and more exposed BP moiety,
      respectively. In addition, the extent of stabilizing interactions between the
      nascent base-pair in each simulation was correlated positively with the
      incorporation preference of that particular nucleotide. The dATP nucleotide is
      accommodated most stably opposite the adduct, with protein-DNA hydrogen bonding
      interactions and an active-site pocket size that do not deviate significantly
      from those of the control simulation. The simulations of dTTP and dGTP opposite
      (+)-trans-anti-[BP]-N(2)-dG exhibited more instability in interactions between
      the protein and the nascent base-pair than the dATP system. However, the active
      site pocket size of the dTTP and dGTP simulations remained stable. The dCTP: (+)
      trans-anti-[BP]-N(2)-dG system had the least number of stabilizing interactions,
      and the active-site pocket of this system increased in size significantly
      compared to the control and other dNTPs opposite the adduct. These simulations
      elucidated why A is inserted opposite (+)-trans-anti-[BP]-N(2)-dG most
      frequently, while T and G are inserted opposite the adduct to an extent
      intermediate between A and C, and C is most rarely incorporated. Structural
      rationalization of the incorporation preference opposite (+)-trans-anti-[BP]-N(2)
      dG by T7 DNA polymerase contributes to providing a molecular explanation for
      mutations caused by this carcinogen-DNA adduct in a model system.

PMID- 12217693
TI  - Derepression of bacteriophage mu transposition functions by truncated forms of
      the immunity repressor.
AB  - To trigger bacteriophage Mu transposition and replication in response to
      physiological signals, its immunity repressor must be synchronously inactivated.
      Two repressor mutants (Vir), which have an altered C-terminal domain and are
      highly susceptible to degradation by ClpXP protease, confer a dominant negative
      phenotype by promoting degradation of the wild-type repressor. To search for
      other modified repressors that can induce Mu derepression in vivo and to
      determine what part of the inducing repressor molecules are needed to target the
      unmodified repressor population, repressor peptides with nested deletions
      starting at the C-terminal end were constructed. Such peptides with a C-terminal
      ssrA degradation tag promoted a sharp reduction in cellular levels of full-length
      unmodified repressor, a process largely dependent upon the clpP protease
      function. Only the repressor DNA-binding domain, located at the N-terminal end,
      was required in tagged peptides to target unmodified repressor. In addition, some
      repressor peptides containing the DNA-binding domain promoted derepression
      without the clpP function, being able to promote repressor inactivation without
      promoting its degradation. None of the modified repressors could promote
      derepression if immunity was established by a mutant repressor lacking 18
      residues at its C-terminal end. The results indicate that inducing repressor
      peptides influence the function of the C-terminal domain of the intact repressor,
      a domain that regulates its degradation and DNA binding. They suggest the
      possibility that tagged repressor molecules, produced by stalled ribosomes, can
      be inducers of transposition under starvation conditions.

PMID- 12217694
TI  - Crystal structure of a prostate kallikrein isolated from stallion seminal plasma:
      a homologue of human PSA.
AB  - Prostate-specific kallikrein, a member of the gene family of serine proteases,
      was initially discovered in semen and is the most useful serum marker for
      prostate cancer diagnosis and prognosis. We report the crystal structure at 1.42A
      resolution of horse prostate kallikrein (HPK). This is the first structure of a
      serine protease purified from seminal plasma. HPK shares extensive sequence
      homology with human prostate-specific antigen (PSA), including a predicted
      chymotrypsin-like specificity, as suggested by the presence of a serine residue
      at position S1 of the specificity pocket. In contrast to other kallikreins, HPK
      shows a structurally distinct specificity pocket. Its entrance is blocked by the
      kallikrein loop, suggesting a possible protective or substrate-selective role for
      this loop. The HPK structure seems to be in an inactivated state and further
      processing might be required to allow the binding of substrate molecules. Crystal
      soaking experiments revealed a binding site for Zn(2+) and Hg(2+), two known PSA
      inhibitors.

PMID- 12217696
TI  - A minimized M13 coat protein defines the requirements for assembly into the
      bacteriophage particle.
AB  - The M13 filamentous bacteriophage coat is a symmetric array of several thousand
      alpha-helical major coat proteins (P8) that surround the DNA core. P8 molecules
      initially reside in the host membrane and subsequently transition into their role
      as coat proteins during the phage assembly process. A comprehensive mutational
      analysis of the 50-residue P8 sequence revealed that only a small subset of the
      side-chains were necessary for efficient incorporation into a wild-type (wt)
      coat. In the three-dimensional structure of P8, these side-chains cluster into
      three functional epitopes: a hydrophobic epitope located near the N terminus and
      two epitopes (one hydrophobic and the other basic) located near the C terminus on
      opposite faces of the helix. The results support a model for assembly in which
      the incorporation of P8 is mediated by intermolecular interactions involving
      these functional epitopes. In this model, the N-terminal hydrophobic epitope
      docks with P8 molecules already assembled into the phage particle in the
      periplasm, and the basic epitope interacts with the acidic DNA backbone in the
      cytoplasm. These interactions could facilitate the transition of P8 from the
      membrane into the assembling phage, and the incorporation of a single P8 would be
      completed by the docking of additional P8 molecules with the second hydrophobic
      epitope at the C terminus. We constructed a minimized P8 that contained only nine
      non-Ala side-chains yet retained all three functional epitopes. The minimized P8
      assembled into the wt coat almost as efficiently as wt P8, thus defining the
      minimum requirements for protein incorporation into the filamentous phage coat.
      The results suggest possible mechanisms of natural viral evolution and establish
      guidelines for the artificial evolution of improved coat proteins for phage
      display technology.

PMID- 12217695
TI  - A model binding site for testing scoring functions in molecular docking.
AB  - Prediction of interaction energies between ligands and their receptors remains a
      major challenge for structure-based inhibitor discovery. Much effort has been
      devoted to developing scoring schemes that can successfully rank the affinities
      of a diverse set of possible ligands to a binding site for which the structure is
      known. To test these scoring functions, well-characterized experimental systems
      can be very useful. Here, mutation-created binding sites in T4 lysozyme were used
      to investigate how the quality of atomic charges and solvation energies affects
      molecular docking. Atomic charges and solvation energies were calculated for
      172,118 molecules in the Available Chemicals Directory using a semi-empirical
      quantum mechanical approach by the program AMSOL. The database was first screened
      against the apolar cavity site created by the mutation Leu99Ala (L99A). Compared
      to the electronegativity-based charges that are widely used, the new charges and
      desolvation energies improved ranking of known apolar ligands, and better
      distinguished them from more polar isosteres that are not observed to bind. To
      investigate whether the new charges had predictive value, the non-polar residue
      Met102, which forms part of the binding site, was changed to the polar residue
      glutamine. The structure of the resulting Leu99Ala and Met102Gln double mutant of
      T4 lysozyme (L99A/M102Q) was determined and the docking calculation was repeated
      for the new site. Seven representative polar molecules that preferentially docked
      to the polar versus the apolar binding site were tested experimentally. All seven
      bind to the polar cavity (L99A/M102Q) but do not detectably bind to the apolar
      cavity (L99A). Five ligand-bound structures of L99A/M102Q were determined by X
      ray crystallography. Docking predictions corresponded to the crystallographic
      results to within 0.4A RMSD. Improved treatment of partial atomic charges and
      desolvation energies in database docking appears feasible and leads to better
      distinction of true ligands. Simple model binding sites, such as L99A and its
      more polar variants, may find broad use in the development and testing of docking
      algorithms.

PMID- 12217697
TI  - Molecular mechanism of the ATP synthase's F(o) motor probed by mutational
      analyses of subunit a.
AB  - The most prominent residue of subunit a of the F(1)F(o) ATP synthase is a
      universally conserved arginine (aR227 in Propionigenium modestum), which was
      reported to permit no substitution with retention of ATP synthesis or H(+)
      coupled ATP hydrolysis activity. We show here that ATP synthases with R227K or
      R227H mutations in the P.modestum a subunit catalyse ATP-driven Na(+) transport
      above or below pH 8.0, respectively. Reconstituted F(o) with either mutation
      catalysed 22Na(+)(out)/Na(+)(in) exchange with similar pH profiles as found in
      ATP-driven Na(+) transport. ATP synthase with an aR227A substitution catalysed
      Na(+)-dependent ATP hydrolysis, which was completely inhibited by
      dicyclohexylcarbodiimide, but not coupled to Na(+) transport. This suggests that
      in the mutant the dissociation of Na(+) becomes more difficult and that the
      alkali ions remain therefore permanently bound to the c subunit sites. The
      reconstituted mutant enzyme was also able to synthesise ATP in the presence of a
      membrane potential, which stopped at elevated external Na(+) concentrations.
      These observations reinforce the importance of aR227 to facilitate the
      dissociation of Na(+) from approaching rotor sites. This task of aR227 was
      corroborated by other results with the aR227A mutant: (i) after reconstitution
      into liposomes, F(o) with the aR227A mutation did not catalyse
      22Na(+)(out)/Na(+)(in) exchange at high internal sodium concentrations, and (ii)
      at a constant (Delta)pNa(+), 22Na(+) uptake was inhibited at elevated internal
      Na(+) concentrations. Hence, in mutant aR227A, sodium ions can only dissociate
      from their rotor sites into a reservoir of low sodium ion concentration, whereas
      in the wild-type the positively charged aR227 allows the dissociation of Na(+)
      even into compartments of high Na(+) concentration.

PMID- 12217698
TI  - Dependence of alpha-synuclein aggregate morphology on solution conditions.
AB  - Alpha-synuclein is the major component of Lewy bodies and Lewy neurites, which
      are granular and filamentous protein inclusions that are the defining
      pathological features of several neurodegenerative conditions such as Parkinson's
      disease. Fibrillar aggregates formed from alpha-synuclein in vitro resemble brain
      derived material, but the role of such aggregates in the etiology of Parkinson's
      disease and their relation to the toxic molecular species remain unclear. In this
      study, we investigated the effects of pH and salt concentration on the in vitro
      assembly of human wild-type alpha-synuclein, particularly with regard to
      aggregation rate and aggregate morphology. Aggregates formed at pH 7.0 and pH 6.0
      in the absence of NaCl and MgCl(2) were fibrillar; the pH 6.0 fibrils displayed a
      helical twist, as clearly evident by scanning force and electron microscopy.
      Incubations at pH 7.0 remained transparent during the process of aggregation and
      exhibited strong thioflavin-T and weak 8-anilino-1-naphthalenesulfonate (ANS)
      binding; furthermore, they were efficient in seeding fibrillization of fresh
      solutions. In contrast, incubating alpha-synuclein at low pH (pH 4.0 or pH 5.0)
      resulted in the rapid formation of turbid suspensions characterized by strong ANS
      binding, reduced thioflavin-T binding and reduced seeding efficiency. At pH 4.0,
      fibril formation was abrogated; instead, very large aggregates (dimensions
      approximately 100 microm) of amorphous appearance were visible by light
      microscopy. As with acidic conditions, addition of 0.2M NaCl or 10mM MgCl(2) to
      pH 7.0 incubations led to a shorter aggregation lag time and formation of large,
      amorphous aggregates. These results demonstrate that the morphology of alpha
      synuclein aggregates is highly sensitive to solution conditions, implying that
      the fibrillar state does not necessarily represent the predominant or most
      functionally significant aggregated state under physiological conditions.

PMID- 12217699
TI  - Sickle hemoglobin fibers: mechanisms of depolymerization.
AB  - We examined the depolymerization of hemoglobin (Hb) S fibers in the presence of
      CO by using photolysis of COHbS to create and isolate individual fibers, then
      removing photolysis to induce depolymerization. Depolymerization occurs at two
      sites, fiber ends and fiber sides, with different kinetics and by different
      mechanisms. At low partial pressure of CO (pCO), end-depolymerization is
      dominant, proceeding at approximately 1 microm s(-1), whereas at high pCO fibers
      vanish very rapidly, in much less than one second, by side-depolymerization. Each
      kind of depolymerization could occur by a ligand-independent path, in which
      deoxyHb depolymerizes and then is prevented from returning to the polymer by
      liganding with CO, or by a ligand-dependent path in which CO binds to the polymer
      inducing dissociation of the newly liganded molecules from it. We find that
      ligand-independent depolymerization is the dominant path for end-depolymerization
      and ligand-dependent depolymerization dominates, at least at high pCO, for side
      depolymerization. On the basis of our kinetic results and electron micrographs of
      depolymerizing fibers, we propose a model for side-depolymerization in which a
      hole is nucleated by cooperative loss of a few molecules from fiber sides,
      followed by rapid depolymerization from the newly created fiber ends abutting the
      hole. Potential significance of these results for the pathophysiology of sickle
      cell disease is discussed.

PMID- 12217700
TI  - Enzymatic catalysis in crystals of Escherichia coli maltodextrin phosphorylase.
AB  - The bacterial enzyme maltodextrin phosphorylase (MalP) catalyses the
      phosphorolysis of an alpha-1,4-glycosidic bond in maltodextrins, removing the non
      reducing glucosyl residues of linear oligosaccharides as glucose-1-phosphate
      (Glc1P). In contrast to the well-studied muscle glycogen phosphorylase (GP), MalP
      exhibits no allosteric properties and has a higher affinity for linear
      oligosaccharides than GP. We have used MalP as a model system to study catalysis
      in the crystal in the direction of maltodextrin synthesis. The 2.0A crystal
      structure of the MalP/Glc1P binary complex shows that the Glc1P substrate adopts
      a conformation seen previously with both inactive and active forms of mammalian
      GP, with the phosphate group not in close contact with the 5'-phosphate group of
      the essential pyridoxal phosphate (PLP) cofactor. In the active MalP enzyme, the
      residue Arg569 stabilizes the negative-charged Glc1P, whereas in the inactive
      form of GP this key residue is held away from the catalytic site by loop 280s and
      an allosteric transition of the mammalian enzyme is required for activation. The
      comparison between MalP structures shows that His377, through a hydrogen bond
      with the 6-hydroxyl group of Glc1P substrate, triggers a conformational change of
      the 380s loop. This mobile region folds over the catalytic site and contributes
      to the specific recognition of the oligosaccharide and to the synergism between
      substrates in promoting the formation of the MalP ternary complex. The structures
      solved after the diffusion of oligosaccharides (either maltotetraose, G4 or
      maltopentaose, G5) into MalP/Glc1P crystals show the formation of phosphate and
      elongation of the oligosaccharide chain. These structures, refined at 1.8A and at
      2.2A, confirm that only when an oligosaccharide is bound to the catalytic site
      will Glc1P bend its phosphate group down so it can contact the PLP 5' phosphate
      group and promote catalysis. The relatively large oligosaccharide substrates can
      diffuse quickly into the MalP/Glc1P crystals and the enzymatic reaction can occur
      without significant crystal damage. These structures obtained before and after
      catalysis have been used as frames of a molecular movie. This movie reveals the
      relative positions of substrates in the catalytic channel and shows a minimal
      movement of the protein, involving mainly Arg569, which tracks the substrate
      phosphate group.

PMID- 12217701
TI  - Detection and characterization of xenon-binding sites in proteins by 129Xe NMR
      spectroscopy.
AB  - Xenon-binding sites in proteins have led to a number of applications of xenon in
      biochemical and structural studies. Here we further develop the utility of 129Xe
      NMR in characterizing specific xenon-protein interactions. The sensitivity of the
      129Xe chemical shift to its local environment and the intense signals attainable
      by optical pumping make xenon a useful NMR reporter of its own interactions with
      proteins. A method for detecting specific xenon-binding interactions by analysis
      of 129Xe chemical shift data is illustrated using the maltose binding protein
      (MBP) from Escherichia coli as an example. The crystal structure of MBP in the
      presence of 8atm of xenon confirms the binding site determined from NMR data.
      Changes in the structure of the xenon-binding cavity upon the binding of maltose
      by the protein can account for the sensitivity of the 129Xe chemical shift to MBP
      conformation. 129Xe NMR data for xenon in solution with a number of cavity
      containing phage T4 lysozyme mutants show that xenon can report on cavity
      structure. In particular, a correlation exists between cavity size and the
      binding-induced 129Xe chemical shift. Further applications of 129Xe NMR to
      biochemical assays, including the screening of proteins for xenon binding for
      crystallography are considered.

PMID- 12217702
TI  - Structure and orientation of a G protein fragment in the receptor bound state
      from residual dipolar couplings.
AB  - Residual dipolar couplings for a ligand that is in fast exchange between a free
      state and a state where it is bound to a macroscopically ordered membrane protein
      carry precise information on the structure and orientation of the bound ligand.
      The couplings originate in the bound state but can be detected on the free ligand
      using standard high resolution NMR. This approach is used to study an analog of
      the C-terminal undecapeptide of the alpha-subunit of the heterotrimeric G protein
      transducin when bound to photo-activated rhodopsin. Rhodopsin is the major
      constituent of disk-shaped membrane vesicles from rod outer segments of bovine
      retinas, which align spontaneously in the NMR magnet. Photo-activation of
      rhodopsin triggers transient binding of the peptide, resulting in measurable
      dipolar contributions to 1J(NH) and 1J(CH) splittings. These dipolar couplings
      report on the time-averaged orientation of bond vectors in the bound peptide
      relative to the magnetic field, i.e. relative to the membrane normal. Approximate
      distance restraints of the bound conformation were derived from transferred NOEs,
      as measured from the difference of NOESY spectra recorded prior to and after
      photo-activation. The N-terminal eight residues of the bound undecapeptide adopt
      a near-ideal alpha-helical conformation. The helix is terminated by an alpha(L)
      type C-cap, with Gly9 at the C' position in the center of the reverse turn. The
      angle between the helix axis and the membrane normal is 40 degrees (+/-4)
      degrees. Peptide protons that make close contact with the receptor are identified
      by analysis of the NOESY cross-relaxation pattern and include the hydrophobic C
      terminus of the peptide.

PMID- 12217703
TI  - Simple physical models connect theory and experiment in protein folding kinetics.
AB  - Our understanding of the principles underlying the protein-folding problem can be
      tested by developing and characterizing simple models that make predictions which
      can be compared to experimental data. Here we extend our earlier model of folding
      free energy landscapes, in which each residue is considered to be either folded
      as in the native state or completely disordered, by investigating the role of
      additional factors representing hydrogen bonding and backbone torsion strain, and
      by using a hybrid between the master equation approach and the simple transition
      state theory to evaluate kinetics near the free energy barrier in greater detail.
      Model calculations of folding phi-values are compared to experimental data for 19
      proteins, and for more than half of these, experimental data are reproduced with
      correlation coefficients between r=0.41 and 0.88; calculations of transition
      state free energy barriers correlate with rates measured for 37 single domain
      proteins (r=0.69). The model provides insight into the contribution of
      alternative-folding pathways, the validity of quasi-equilibrium treatments of the
      folding landscape, and the magnitude of the Arrhenius prefactor for protein
      folding. Finally, we discuss the limitations of simple native-state-based models,
      and as a more general test of such models, provide predictions of folding rates
      and mechanisms for a comprehensive set of over 400 small protein domains of known
      structure.

PMID- 12217706
TI  - Seal finger--tetracycline is first line.

PMID- 12217707
TI  - Spinal epidural abscess--experience with 46 patients and evaluation of prognostic
      factors.
AB  - OBJECTIVE: Spinal epidural abscess is a rare infectious disorder, often with a
      delayed diagnosis, and associated with significant morbidity and mortality rates.
      We conducted a retrospective study to define its clinical characteristics and to
      evaluate its prognostic factors. METHODS: The medical charts of 46 patients (36
      men and 10 women) with spinal epidural abscess over a 10-year period (from July
      1991 to May 2000) were reviewed and analyzed. RESULTS: A high proportion of
      patients had underlying diseases of diabetes (46%), frequent venous puncture
      (35%), spinal trauma (24%), and history of spinal surgery (22%). The initial
      accurate diagnostic rate was 11%. Localized spinal pain (89%), paralysis (80%),
      fever/chills (67%), and radicular pain (57%) were the common manifestations. The
      erythrocyte sedimentation rate (ESR) was elevated uniformly (mean, 86.6 mm/h)
      when measured. Staphylococcus aureus was the most common cause of spinal epidural
      abscess isolated from blood (39%) and pus (50%). Low platelet counts (< 100 x
      10(9)/L) (odds ratio (OR): 8.8, 95% confidence interval (CI): 1.0-77.8),
      extremely high ESR (> or = 110 mm/h) (OR: 4.8, 95% CI: 0.9-25.4), and cervical
      spine epidural abscess (OR: 5.2, 95% CI: 0.8-32.0) predicted a poor outcome.
      CONCLUSIONS: Localized back pain in a febrile patient with significant risk for
      epidural abscess warrants an immediate magnetic resonance imaging examination.
      The presence of thrombocytopenia, extremely elevated ESR, or evidence of spinal
      cord compression should prompt aggressive treatment.

PMID- 12217708
TI  - Epidemiology and control of tuberculosis in Taipei.
AB  - OBJECTIVES: This retrospective study evaluated epidemiological trends in
      tuberculosis and the performance of a TB control program in Taipei. METHODS: Data
      of all recorded tuberculosis cases from 1994 through 2000 obtained from the
      Tuberculosis Registry Center was used to analyze the trend of incidence.
      Tuberculin skin tests were also performed to estimate the prevalence and annual
      risk of tuberculosis infection in second-grade schoolchildren during the period
      1996-1999. The management cards for all tuberculosis patients from 1992 to 1996
      obtained from Taipei Municipal Chronic Disease Hospital were also reviewed.
      RESULTS: The results show that incidence of tuberculosis had an increasing trend
      during the study periods with an average annual increase of 7.73% and 9.93% for
      males and females, respectively. Age-specific incidence showed a similar trend
      with a clear predominance of cases occurring in patients aged 25-34 and 65+
      years. This bimodal pattern became more apparent in 2000. In second-grade
      schoolchildren, the annual risk of tuberculosis infection was approximately 0.68%
      with a decreasing trend over the study period. The relatively low cure rate of
      TB, averaging 47.2%, did not change significantly during the study period. Cure
      rate was significantly associated with patient's age, patient status as a new or
      recurrent case, and the development of side effects due to treatment with
      antituberculosis drugs. CONCLUSIONS: Because of the low overall cure rate of
      47.2%, this region of Taipei remains high TB rates. The inefficiency of the
      existing tuberculosis control program is largely to blame for the alarmingly high
      rates. The high percentage of recurrent cases and of cases in individuals aged 25
      34 and older than 65 present a severe challenge to effective management and form
      a chronic pool of infectious cases. Our findings suggest that in order to achieve
      the WHO target of cure in 85% of TB cases, focusing effort on the identification
      and treatment of these groups is mandatory.

PMID- 12217709
TI  - Outcome of the treatment of culture negative tuberculosis (respiratory and non
      respiratory): Blackburn 1996-2000.
AB  - OBJECTIVE: To determine the outcome of treating patients without culture
      confirmation of tuberculosis, with a regimen of two months of isoniazid,
      rifampicin, pyrazinamide and ethambutol followed by four months of isoniazid and
      rifampicin (2HRZE/4HR) in a setting with a rate of isoniazid resistance of 7.5%
      in culture confirmed cases. SETTING: Tuberculosis patients treated in the
      Blackburn, Hyndburn and Ribble Valley districts of the UK between 1996 and 2000
      inclusive. METHODS: Patients from a detailed prospective clinical and
      epidemiological data base for all tuberculosis patients were studied for the
      years 1996-2000. RESULTS: One hundred and fourteen cases, all but two of Indian
      subcontinent ethnic origin, without culture confirmation had received 2HRZE/4HR.
      Twenty had pulmonary, 55 other respiratory and 39 non-respiratory tuberculosis.
      There was no bacteriologically confirmed relapse, 1 case was retreated as a
      clinical relapse. CONCLUSION: The treatment of tuberculosis cases without culture
      confirmation with a regimen of 2HRZE/4HR gives highly acceptable results. The
      clinical relapse rate was 0.85% (1/114), and the cure rate 99.15%.

PMID- 12217710
TI  - Vancomycin sequestration during cardiopulmonary bypass surgery.
AB  - OBJECTIVE: The present study was designed to analyze vancomycin disposition in
      adult patients undergoing coronary bypass grafting during and following
      cardiopulmonary bypass (CPB). METHODS: Coronary bypass surgery was performed on
      11 adults with a mean age (SD) of 62.9 (9.0) years old, who received a mean (SD)
      vancomycin prophylactic dose of 12.7 (1.0) mg/kg in a mean period of 41 (0.7)
      min. Using a two-compartment open model for pharmacokinetic analysis, the
      following parameters were obtained: alpha half-life, minutes (t(1/2alpha)); beta
      half-life, hours (t(1/2beta)); apparent volume of distribution, (V(d) l/kg);
      volume of the central compartment, (V(c) l/kg), constant between the "central to
      the peripheral" compartment, (k(12)); constant between the "peripheral to the
      central" compartment, (k(21)); total area under the concentration-time curve,
      (AUC mg/lxh) and a vancomycin clearance, (Cl(van) ml/min), respectively. RESULTS:
      The mean (SD) calculated pharmacokinetic parameters were: t(1/2alpha)17.6 (6)
      min, t(1/2beta) 8.4 (3.8) h, V(d) 0.803 (0.259) l/kg, V(c) 0.270 (0.162) l/kg,
      k(12) 0.03 (0.015), k(21) 0.012 (0.012), total AUC 10377.2 (3687.6) mg/lxh. The
      mean (SD) vancomycin clearance by the CPB machine was 9.51 (2.66) l/h, and the
      mean (SD) total vancomycin sequestrated by CPB was 331.7 (84) mg. A significant
      difference (6.3%; p = 0.001) was measured between the mean measured AUC during
      CPB (1088.1 +/- 253.9) and the same calculated parameter (1160.2 +/- 282). Five
      minutes after starting CPB, a decrease in vancomycin level was detected; this
      difference was found to be nearly 11% in absolute values. CONCLUSIONS: This
      confirmatory study demonstrated that the vancomycin blood concentrations obtained
      during the study allow recommending a safety prophylactic dose of 12mg/kg in
      adults who undergo open-heart surgery under CPB conditions. Sequestration of
      vancomycin by the oxygenator or/and tubing system of the CPB machine had occurred
      and had been measured in this study.

PMID- 12217711
TI  - Fulminant hepatic failure and autoimmune hemolytic anemia associated with Epstein
      Barr virus infection.
AB  - Acute hepatic failure has been reported in the presence of Epstein-Barr virus
      (EBV) infection. Autoimmune hemolytic anemia may also occur in the course of this
      infection. We report a rare case of fulminant hepatic failure and autoimmune
      hemolytic anemia associated with Epstein-Barr virus. A seven-year-old girl was
      admitted with the complaints of abdominal pain, vomiting and jaundice. She was
      irritable, confused and had mild hepatomegaly with marked splenomegaly. Serum
      aminotransferase levels were moderately elevated, while direct and indirect
      bilirubin levels were markedly elevated. Prothrombin time was prolonged.
      Hemoglobin was 3.9 g/dl. Anti-HAV IgM, HbsAg, anti-HBc IgM, anti-HCV and anti-CMV
      IgM were negative, while IgM VCA EBV, IgG VCA EBV and anti-CMV IgG were positive.
      Serum copper and ceruloplasmin levels were normal. The patient received
      supportive therapy for hepatic failure. Meanwhile, the cause of the deep anemia
      was investigated and autoimmune hemolytic anemia was ascertained by means of
      increased reticulocyte count and positive Coombs test. Corticosteroid therapy was
      administered. The prognosis was good. Although not reported before, the
      combination of acute hepatic failure and autoimmune hemolytic anemia may
      complicate the course of EBV infection. Physicians need to be aware of this
      association.

PMID- 12217712
TI  - Diarrhea, CD4 counts and enteric infections in a community-based cohort of HIV
      infected adults in Uganda.
AB  - OBJECTIVES: To examine relationships between diarrhoea, CD4 cell counts and stool
      pathogens in a community-based cohort of HIV-infected adults in Uganda. PATIENTS
      AND METHODS: Stool specimens, obtained between October 1995 and December 1997,
      were linked to patients' symptoms and laboratory results. The relationship
      between CD4 counts and symptoms was tested using the Wilcoxon rank-sum test and
      those between organisms and diarrhoea using first a univariate Mantel-Haenszel
      analysis and then a logistic regression model adjusted for CD4 count and multiple
      organisms. RESULTS: 1,213 HIV-infected individuals (70% women, median CD4 cell
      count at enrollment 215 cells/microl) were followed for 1,224 person years of
      observation (pyo). 484 stool samples were examined, 357 from patients with
      diarrhoea. The rate of diarrhoea was 661 episodes per 1,000 pyo. CD4 counts were
      significantly lower in individuals with diarrhoea than those without (P < 0.001,
      Wilcoxon rank-sum test). Forty-nine percent of diarrhoeal stools and 39% of
      stools from asymptomatic patients contained enteric pathogens. The most frequent
      isolates were helminths (29.5% of all stools), followed by bacteria (19.2%) and
      then protozoa (8.9%). Rates of isolation of diarrhoea-associated pathogens were
      29% from diarrhoeal stools and 17% from asymptomatic stools (P = 0.01, chi(2)
      test). The association between diarrhoea and infection with bacteria or protozoa
      was weak and there was no association with helminths. Cryptosporidium parvum
      infection alone was associated with low CD4 counts. CONCLUSIONS: Diarrhoea was
      common and most strongly associated with low CD4 counts. Bacteria were frequently
      found, even in stools from asymptomatic individuals. Over two-thirds of
      diarrhoeal episodes were undiagnosed, suggesting that unidentified agents or
      primary HIV enteropathy are important causes of diarrhoea in this population.

PMID- 12217713
TI  - The changing epidemiology of infectious mononucleosis?

PMID- 12217714
TI  - Serological evidence of hantavirus in humans and rodents in Barbados.

PMID- 12217715
TI  - Anaerobic infection of the lumbar spine in an intravenous drug abuser.

PMID- 12217716
TI  - BCG septicemia after radical cystectomy: a rare postoperative complication
      following BCG therapy.
AB  - It is reported a case of life-threatening septic shock due to BCG septicemia
      after radical cystectomy in a patient with a previous treatment with BCG therapy.
      In the absence of response to standard antimicrobial therapy and a negative CT
      scan, a PCR-based technique detected the presence of BCG bacilli in bloodstream.
      Immediate antimycobacterial therapy resolved the sepsis, thus suggesting either
      the awareness of this infection or the prompt antimycobacterial therapy as the
      key for the appropriate management. Furthermore, isoniazid prophylaxis should be
      taken into consideration in patients with history of intravesical BCG therapy
      undergoing cystectomy.

PMID- 12217717
TI  - Lemierre's disease caused by co-infection of Arcanobacterium haemolyticum and
      Fusobacterium necrophorum: a case report.
AB  - We report the first case of Lemierre's disease caused by a co-infection with A.
      haemolyticum and F. necrophorum. A characteristic skin rash and predominant
      growth on multiple blood cultures suggests a causative role for Arcanobacterium.
      Failures of penicillin therapy in A. haemolyticum infections should be considered
      when the initial antibiotic regimen is chosen.

PMID- 12217718
TI  - Eosinophilic meningitis due to Gnathostoma spinigerum.
AB  - We present a case of eosinophilic meningitis due to the tissue nematode
      Gnathostoma spinigerum in a patient with remote travel to Korea. G. spinigerum is
      found primarily in Southeast Asia, but cases are being increasingly diagnosed in
      non-endemic areas because of more extensive international travel. The organism
      has been known to persist in human tissues for over a decade, so earlier travel
      to endemic areas is important.

PMID- 12217719
TI  - A mass in the liver.
AB  - We report a case of alveolar echinococcosis. To our knowledge this is the first
      report of human alveolar echinococcosis to be confirmed in the UK and if
      contracted in Afghanistan the first report for that country.

PMID- 12217720
TI  - Bacteria in two-millennia-old cheese, and related epizoonoses in Roman
      populations.
AB  - A tremendous volcanic eruption destroyed all the life around Mount Vesuvius
      during the night between 24 and 25 August, 79 AD. Two famous towns, Pompeii and
      Herculaneum, were completely buried under volcanic products. At Herculaneum,
      about 25m of volcanic mud killed about 250 people who had fled to the beaches in
      an attempt to escape (Bisel, S. C.,Rivista di Studi Pompeiani, 1, 123-124, 1987).
      An anthropological examination of the skeletons of these "fugitives" reveals the
      bone lesions typical of brucellosis in 17.4% of adults (Capasso, L.,
      International Journal of Osteoarchaelogy, 9, 277-288, 1999). This very high
      incidence of brucellosis was theoretically linked to the consumption of ovine
      milk and its derivates, which is also indicated by both literary and figurative
      sources. A single carbonized cheese was found in Herculaneum; its analysis
      clearly reveals the excellent state of preservation of the milk curds. For the
      first time, we demonstrate the presence of a variety of bacteria, possibly
      Lactobacillus, that also includes cocco-like forms that seem to be
      morphologically and dimensionally consistent with Brucella. The long interval
      spent by the organic remains under the volcanic mud and high temperatures they
      suffered preclude the possibility of identifying the bacteria through molecular
      methods.

PMID- 12217721
TI  - Doxycycline and chloroquine as treatment for chronic Q fever endocarditis.
AB  - Endocarditis is a rare but severe complication of Q fever, an infectious disease
      caused by the intracellular pathogen Coxiella burnetii. Heart involvement is the
      most common clinical presentation of chronic Q fever, and it occurs almost
      invariably in patients with previous valvular disease or artificial valves, and
      in the immunocompromised host. The optimal treatment of Q fever endocarditis is
      still today debated, and recommended duration of treatment varies from one year
      to one's lifespan. A case of chronic Q fever endocarditis is described in a
      patient with biological prosthetic aortic valve and aortic homograft,
      successfully treated with doxycycline and chloroquine for 2 years.

PMID- 12217722
TI  - Treatment of Staphylococcus epidermidis ventriculo-peritoneal shunt infection
      with linezolid.
AB  - Gram-positive bacterial meningitis frequently complicates ventriculo-peritoneal
      (VP) shunts used for hydrocephalus. Linezolid, an oxazolidinone, is active
      against Gram-positive cocci, and has excellent CSF penetration. We present a 22
      year-old woman who was cured of a Staphylococcus epidermidis VP shunt infection
      via shunt removal and intravenous linezolid.

PMID- 12217723
TI  - Antibiogram pattern of Salmonella species causing bacteraemia/septicaemia in a
      teaching hospital.

PMID- 12217724
TI  - Rotavirus vaccines: development, current issues and future prospects.
AB  - The potential benefit of safe and effective rotavirus vaccination in reducing
      morbidity and especially mortality from rotavirus gastroenteritis among children
      in developing countries has long been recognised. More recently, the focus of
      attention shifted to developed countries, where cost-effectiveness analyses
      justified the routine introduction of rotavirus vaccines into childhood
      immunisation schedules. The recent withdrawal in the U.S.A. of the first licensed
      rotavirus vaccine (the tetravalent rhesus reassortant rotavirus vaccine),
      following investigation into reports of intussusception among a number of
      vaccinees, has directed attention once more towards rotavirus vaccine use in
      developing countries. However, issues relating to vaccine safety, efficacy, and
      cost, remain to be overcome before widespread introduction of rotavirus vaccines
      can be anticipated.

PMID- 12217725
TI  - Respiratory syncytial virus infections in children and adults.
AB  - Respiratory syncytial virus is the leading cause of hospital admission for lower
      respiratory tract infection in young children and appears to be responsible for a
      significant burden of disease in adults, particularly the elderly and the
      immunocompromised. In this review, we describe the epidemiology, diagnosis and
      clinical manifestations of infection attributed to this virus. We also consider
      current therapeutic and prophylactic options and appraise strategies for
      vaccination that are in clinical trials.

PMID- 12217726
TI  - Respiratory syncytial virus--viral biology and the host response.
AB  - Respiratory syncytial virus (RSV) is the most important cause of respiratory
      tract infection in infants. We have an incomplete understanding of the reasons
      why some infants are more severely affected by RSV than others. There is no
      effective antiviral treatment for the infection. Advances in our understanding of
      the biology of RSV, particularly in relation to the attachment protein G and the
      fusion protein F, have revealed potential targets for new antiviral therapies and
      vaccine development. In response to RSV infection an intense inflammatory
      response is triggered, mediated initially by the infected airway epithelial
      cells. Cell mediated responses are important in controlling the extent of
      infection and in viral clearance. Humoral responses are important in protection.
      There is early evidence that genetic variation of the host response can influence
      the outcome of RSV-induced bronchiolitis.

PMID- 12217727
TI  - Trends in the epidemiology of Candida bloodstream infections in Northern Ireland
      between January 1984 and December 2000.
AB  - OBJECTIVE: To describe the epidemiology of Candida bloodstream infections (BSI)
      in Northern Ireland. METHODS: Retrospective collation of data relating to all
      clinically significant BSI in a university teaching hospital, which had been
      recorded prospectively, between 1984 and 2000. RESULTS: One hundred and forty
      five episodes of candidaemia occurred in 144 patients (of mean age 56.6 years).
      The contribution of Candida spp. towards all significant BSI increased from 2.0%
      to 2.5%. C. albicans was the most frequently isolated species, however, its
      incidence fell from 70% to 53% during the study period. The greatest increase in
      incidence was seen with C. glabrata which was the most common non-albicans
      species. Twenty-nine per cent of isolates occurred in patients from an intensive
      care unit and, surprisingly, a further 25.5% occurred in patients from a surgical
      service. CONCLUSION: There appears to be several subtle differences in the
      epidemiology of candidal BSI between Northern Ireland and other countries.

PMID- 12217728
TI  - HTLV-I and HTLV-II infections in volunteer blood donors and high-risk groups in
      Lebanon.
AB  - A serosurvey for Human T-cell Lymphotropic virus type 1 (HTLV-I)/HTLV-II was
      conducted in 1,900 blood donors, 120 pregnant women and 436 high-risk group
      patients in Beirut, Lebanon. One of the 1,900 blood donors was anti-HTLV-I/II
      seroreactive on screening by enzyme immunoassay (EIA) but was indeterminate by
      Western blot and negative by polymerase chain reaction. None of the other 556
      subjects studied was seroreactive by EIA. The credibility of the zero prevalence
      of HTLV-I/II infection among the Lebanese blood donors is supported by the
      absence of seroreactivity of antibodies in the multiply transfused patients. It
      seems therefore that the prevalence of HTLV-I/II appears to be less than 1 in
      2,456 in the Lebanese population and hence, HTLV-I/II infection does not appear
      to require routine screening in Lebanon.

PMID- 12217729
TI  - Anti-septicaemic effect of polysaccharide from Panax ginseng by macrophage
      activation.
AB  - The aim of the present research was conducted to elucidate anti-septicaemic
      effect of a polysaccharide (PS) isolated from Panax ginseng C.A. Meyer
      (Araliaceae) by nitric oxide production from stimulated macrophage. In vitro
      assays for the activity measurement of PS, NO production test with Greiss
      reagent, phagocytic activity test using zymosan and cytokines production test
      using ELISA kit were also conducted. In vivo anti-septicaemic activity was
      assessed by using C57BL/6J mice. This was done with Staphylococcus aureus
      infection test. PS used at 0.025 mg/kg concentration showed a potent anti
      septicaemic activity (80%, survival). However, it did not directly inhibit S.
      aureus in a minimum inhibitory concentration (MIC) test, conducted in vitro (data
      not shown). Nitric oxide production via macrophage activation showed the highest
      value of 5.5 nmol/ml at 1 microg/ml PS. In in vitro phagocytic activity test, PS
      at 10 microg/ml concentration showed a potent phagocytic activity for zymosan
      with 167% of the control. Production of TNF-alpha by macrophage activation at 10
      microg/ml of PS was 96% lysis of L929. Also production of IL-1 and IL-6 by
      stimulation of macrophage with 100 microg/ml PS dose increased to 235 pg/ml and
      0.47 ng/ml, respectively. The low mortality of PS treated (0.025 mg/kg) infected
      mice was concurrent with decreased bacterial content in the blood. Nitric oxide
      production in S. aureus infected mice whose macrophage was stimulated by PS
      (0.025 mg/kg) increased approximately 4 times than the untreated S. aureus
      infected group at 24 and 48 h incubation. In the PS treated (0.025 mg/kg) group,
      the intracellular concentration of S. aureus in macrophages decreased
      approximately by 50%, compared with the untreated group. Combine treatment with
      PS (0.025 mg/kg body weight) and vancomycin (10 mg/kg B.W.) resulted in 100%
      survival of the animals, whereas only 67% or 50% of the animals survived,
      respectively, when treated with PS or vancomycin alone. These results suggest
      that PS from Panax ginseng possess a potent anti-septicaemic activity by
      stimulating macrophage and a potentiality as an immunomodulator against sepsis
      occurred by Staphylococcus aureus.

PMID- 12217730
TI  - Native valve endocarditis due to Streptococcus vestibularis and Streptococcus
      oralis.
AB  - Viridans streptococci are the commonest cause of native valve infective
      endocarditis (IE). The taxonomy of this group is evolving allowing new disease
      associations to be made. Streptococcus vestibularis is a recently described
      member of the viridans group, first isolated from the vestibular mucosa of the
      human oral cavity. It has rarely been associated with human disease.
      Streptococcus oralis, another member of the viridans group resident in the human
      oral cavity is a well known cause of IE and bacteraemia in neutropenic patients.
      We report the first case of native mitral valve endocarditis due to S.
      vestibularis in a patient with co-existing S. oralis endocarditis.

PMID- 12217731
TI  - Group B streptococcal serotype distribution of isolates from colonized pregnant
      women at the time of delivery in United Arab Emirates.
AB  - OBJECTIVE: To determine the maternal colonization rate with group B streptococcus
      (GBS) and to identify the most frequent GBS serotypes occurring in UAE women
      during labour. STUDY DESIGN: From February 1998 to January 1999, five hundred and
      sixty three pregnant women from a similar socio-economic and ethnic population
      were enrolled for the study. High vaginal swab cultures for GBS were obtained at
      the time of admission for delivery. Isolates were classified according to their
      capsular polysaccharide types (Ia, Ib, Ic, II-V) and c protein antigen compound.
      RESULTS: Fifty-seven (10.1%) of 563 mothers were found to be carriers of GBS.
      Among the isolates, serotype IV (26.3%) predominated followed by type Ia (21.0%),
      type III (17.6%), type V (12.3%) and nontypeable, which accounted for 15.8%.
      CONCLUSIONS: In view of the unknown status for GBS carrier rates in our
      community, this study suggests that about 10% of UAE women are colonized with
      group B streptococcus at delivery. The serotype distribution of the isolates in
      this population is different than those reported elsewhere with type IV
      predominating followed by type Ia and III.

PMID- 12217732
TI  - Bacteraemia due to Stenotrophomonas maltophilia: an analysis of 45 episodes.
AB  - OBJECTIVE: Stenotrophomonas maltophilia is an important nosocomial pathogen and a
      therapeutic challenge. A ten-year review of episodes of bacteraemia due to S.
      maltophilia was undertaken in light of reports of an increasing frequency of
      infection. METHODS: A retrospective analysis of bloodstream infections due toS.
      maltophilia at a tertiary care hospital in Melbourne, Australia. Cases were
      identified via microbiology laboratory reports, and relevant clinical data were
      collected from the medical record of each patient. RESULTS: Eighty per cent of
      these 45 episodes were nosocomial. The most common characteristics in cases of
      bacteraemia were the presence of an indwelling central venous catheter (CVC)
      (38/45, 84%) and previous antibiotic therapy (33/45, 73%). There were 8 deaths
      (8/44, 18%) within 7 days of bacteraemia. A significant correlation was found
      between deaths and a failure to remove the CVC (P = 0.01) or treat with
      appropriate antimicrobials (P = 0.01). Antibiotic susceptibility testing revealed
      that isolates were most sensitive to sulphamethoxazole (80%), chloramphenicol
      (75.5%) and ceftazidime (64.5%). CONCLUSIONS: S. maltophilia is an important
      pathogen especially in the highly compromised host. Isolation of this organism
      from a blood culture should prompt a careful review of the patient with
      particular emphasis on removal of indwelling CVCs and commencement of appropriate
      antibiotic therapy.

PMID- 12217733
TI  - The burden of uncomplicated cases of chickenpox in Israel.
AB  - OBJECTIVE: The aim of this study was to assess the direct medical burden and work
      loss associated with uncomplicated chickenpox in Israel. METHODS: A total of 155
      otherwise healthy children and adolescents with chickenpox were recruited from 10
      physician offices in central Israel. Direct and indirect medical burdens were
      determined by caregiver interview. RESULTS: Mean age was 3.3 +/- 2.3 years. 51%
      of the patients were under three years of age. Each patient made on average 1.15
      visits to a general practitioner. Most patients were taken to the Doctor's office
      only once during the illness while 23 patients (15%) were seen twice. Three
      patients were referred to the emergency room. Antihistamines (39%) and Calamine
      lotion (28%) were the most frequently prescribed medications, followed by
      acyclovir (17%) and antibiotics (6%). Following the patient's illness there were
      72 cases of secondary spread of varicella to household members. The individuals
      who cared for the child missed a combined total of 2.5 days from work (on average
      per varicella episode). CONCLUSIONS: Israeli children acquire chickenpox at a
      younger age than children in North America and England and consume more
      prescribed medications. While the work loss in the present study was comparable
      to previous reports, the direct medical costs inflicted by this infection in
      Israel are not negligible even for uncomplicated cases.

PMID- 12217734
TI  - Encephalitis due to a hantavirus infection.

PMID- 12217735
TI  - Role of surgery in Rhodococcus equi pulmonary infections.
AB  - Rhodococcus equi (R. equi) is a soil-dwelling bacterium that is increasingly
      associated with pulmonary infections in immunocompromised patients. While
      antibiotic therapy remains the cornerstone of treatment, surgery combined with
      antibiotics has an important role in select cases. We report two cases of
      pulmonary R. equi in immunocompromised patients who were treated with
      antibiotics, followed by surgical resection of the infected tissues, and then
      long-term antibiotics. Both patients had excellent outcomes. We advocate surgical
      resection of grossly infected pulmonary tissue as an adjunct to antimicrobial
      therapy for treatment of this uncommon, but potentially lethal pathogen.

PMID- 12217736
TI  - Acute demyelinating encephalomyelitis (ADEM) in a patient with HIV infection.
AB  - A case of acute demyelinating encephalomyelitis (ADEM) in a patient with HIV
      infection is reported. Although the diagnosis of ADEM is based on clinical and
      radiological findings, the potential for full recovery, with appropriate
      treatment, is highlighted by this case. A concise review of the subject is given
      in the discussion.

PMID- 12217737
TI  - A proposal for a shorter post-exposure prophylaxis of HIV infection to prevent
      adverse secondary reactions.

PMID- 12217738
TI  - Citrobacter koseri pneumonia and meningitis in an infant.

PMID- 12217739
TI  - Poliomyelitis susceptibility at the South African Virology Institute.

PMID- 12217741
TI  - The prophylactic administration of recombinant erythropoietin in the management
      of ovarian cancer: time for a definitive phase 3 randomized trial.

PMID- 12217742
TI  - Prediction of the need for red cell transfusion in newly diagnosed ovarian cancer
      patients undergoing platinum-based treatment.
AB  - OBJECTIVE: The objective of this study was to develop a predictive algorithm for
      the likelihood of red blood cell transfusion in women with ovarian cancer
      undergoing platinum-based chemotherapy. METHODS: Patients in this analysis came
      from two phase III studies conducted by the Southwest Oncology Group and
      Gynecologic Oncology Group of platinum-based chemotherapy in advanced ovarian
      cancer patients, SWOG 8412 and SWOG 8501/GOG 104. The probability of packed red
      blood cell (PRBC) transfusion was modeled as a function of stage of disease, age,
      weight, creatinine clearance, hemoglobin (Hb) prior to the start of therapy, the
      platinum agent administered (i.e., cisplatin vs carboplatin), and the route of
      drug administration (i.e., intravenous vs intraperitoneal). RESULTS: Overall, 16%
      of patients developed at least grade 3 anemia (Hb < 8 g/dL) during primary
      chemotherapy, with 2% experiencing grade 4 anemia (Hb < 6.5 g/dL). PRBC
      transfusions were administered to 32% of patients. Factors that were determined
      to be predictive of PRBC transfusions were age and baseline Hb. In patients with
      bulky stage III or stage IV disease, the odds of transfusion increased by 66% for
      each 10-year increase in age and by 65% for each 1 g/dL decrease in baseline
      hemoglobin. Thus a patient aged 65 with a baseline Hb of 10.5 g/dL has
      approximately a 40% chance of transfusion. CONCLUSIONS: Older ovarian cancer
      patients (>65 years) with low baseline Hb levels (<10.5) at initiation of
      platinum-based chemotherapy are likely to become more anemic during treatment and
      should be considered for prophylactic erythropoietin therapy as an alternative to
      transfusion.

PMID- 12217743
TI  - The contribution of rapid intraoperative cytology to the improvement of ovarian
      cancer staging.
AB  - OBJECTIVE: The goal of this work was to evaluate the use of intraoperative
      cytology in the improvement of ovarian cancer staging. METHODS: Fifty-two
      patients with clinical stage IA-IIB ovarian cancer underwent peritoneal washing
      (PW) cytology and imprint cytology performed on retroperitoneal lymph node
      samples, during primary surgical treatment. Cytologic specimens were stained by
      the May-Grunwald-Giemsa (MGG) and hematoxylin-eosin (HE) techniques. Pertinent
      histologic sections of the ovarian lesions, cell blocks prepared from PW
      sediments, and lymph node samples were studied and compared with the cytologic
      findings. RESULTS: Our study reveals that, when malignant cells are present in
      the peritoneal cavity, PW cytology has 84.6% sensitivity and 94.7% specificity in
      detecting them. Imprint cytology performed on lymph node samples presented 94.1%
      sensitivity and 94.1% specificity in the diagnosis of retroperitoneal metastasis
      of ovarian cancer. Only 7 patients (13.4%) were upstaged with either cytologic
      method. PW cytology alone upstaged 6 more patients, while imprint cytology alone
      upstaged 11 more patients. This corresponds to a total of 17 patients (32.6%) who
      benefit from the combined performance of both cytologic methods. HE stain
      presents lower values of sensitivity and specificity compared with MGG.
      CONCLUSION: Cytologic evaluation of intraperitoneal and retroperitoneal spread of
      ovarian cancer by use of PW cytology and imprint cytology performed on lymph node
      samples contributes to the improvement of ovarian cancer staging.

PMID- 12217744
TI  - Influence of estradiol and gestagens on oxidative stress in the rat uterus.
AB  - OBJECTIVE: We studied the effect of ovariectomy, estradiol (E2), and E2 +
      medroxyprogesterone (MPA) on the Wistar rat uterus. METHODS: We used 15 adult
      female rats. The study was divided into the following four stages: (a)
      extirpation of the upper half of the left hemi-uterus (basal state) and
      ovariectomy; (b) animals were maintained for 15 days without treatment,
      performance of a new laparotomy, and extirpation of the remaining left hemi
      uterus (OVX state); (c) beginning of E2 replacement therapy (ERT) (8 microg/day)
      for 15 days, followed by extirpation of the upper half of the right hemi-uterus
      (ERT state); and (d) the administration of E2 was continued, and oral treatment
      with MPA was begun (20 microg/day) to last for a further 15 days. At the end of
      the combined hormone replacement therapy (HRT) the remaining right hemi-uterus
      was extirpated (HRT state). At the end of each intervention, the plasma
      concentrations of E2 and PRG were measured. RESULTS AND DISCUSSION: The
      ovariectomy significantly reduced the malonaldehyde (MDA) levels (P < 0.0008) and
      catalase activity (P < 0.0006). The ERT very significantly (P < 0.0033) raised
      the catalase and MDA levels; these significance levels were maintained after the
      Bonferroni method was applied (overall error 5%). The HRT reduced the levels of
      MDA and catalase, but not significantly after the Bonferroni test was
      applied.Conclusions. Uterine oxidative stress is increased by E2, resulting in a
      significant increase in MDA. This may be modulated in part by the catalase
      activity. Although it cannot be confirmed categorically, MPA seems to intervene
      by decreasing the said oxidative stress.

PMID- 12217745
TI  - Is there a survival benefit to adjuvant radiotherapy in high-risk surgical stage
      I endometrial cancer?
AB  - OBJECTIVE: The aim of this study was to examine the effects of therapeutic
      modalities on survival of stage I endometrial cancer and also to evaluate the
      surgical morbidity and the prognostic importance of surgicopathological
      variables. METHODS: A hundred and ninety-six stage I endometrial cancer patients
      treated at Hacettepe University Hospital between 1982 and 1997 were included.
      After initial diagnosis all patients underwent surgical procedures including
      peritoneal cytology, infracolic omentectomy, total abdominal hysterectomy,
      bilateral salphingoopherectomy, and complete pelvic-paraaortic lymphadenectomy.
      The mean age at initial diagnosis was 56 years (SD = 9.9 years) and the patients
      were followed 3-18 years (median, 8 years). All patients had endometrioid
      carcinoma. Stage IC and/or grade 3 tumors were considered high-risk factors and
      by this definition 147 (75%) patients were low risk and 49 (25%) patients were
      high risk. Forty-nine percent of high-risk patients received adjuvant
      radiotherapy compared with 3.5% of patients in the low-risk group. RESULTS: The
      10-year disease-free and overall survival rates of the entire group were 97 and
      98%, respectively. Ten-year overall survival rate for the low-risk group was 100%
      compared with 94% for patients with high-risk features (P = 0.002). The 10-year
      disease-free survival rate in the high-risk group was 96% for 24 patients who
      received adjuvant radiotherapy versus 92% for 25 patients who did not receive
      adjuvant therapy (P = 0.53). Only high grade was a significant predictor of poor
      survival (P = 0.0004). Overall surgical morbidity rate was 8.1% without mortality
      related to surgery. CONCLUSIONS: Surgical staging achieved excellent survival for
      stage I endometrial cancer patients without incurring untoward morbidity and
      mortality. No survival advantage of adjuvant radiotherapy was detected even for
      high-risk patients, so we suggest the use of radiotherapy may be reserved for
      relapse.

PMID- 12217746
TI  - Pelvic insufficiency fracture after pelvic irradiation in uterine cervix cancer.
AB  - OBJECTIVES: Pelvic insufficiency fractures (IF) are well known but uncommon and
      are frequently misinterpreted sequelae. The clinical features were investigated.
      METHODS: Four hundred sixty-three patients, who were treated between 1994 and
      2000 for uterine cervix cancer, were clinically examined. All patients had been
      treated with 10 or 15 MV photons, with 50.4-55.8 Gy in 28 fractions with adjuvant
      intent (n = 235) in addition to high-dose-rate brachytherapy 24 Gy in 6 fractions
      for curative treatment (n = 228). The median follow-up was 38 months. RESULTS:
      Eight patients (8/463, 1.7%) developed pelvic IF 7-19 months (median, 12 months)
      after the treatment. Among these, seven patients (7/228, 3.1%) were treated with
      curative intent and one (1/235, 0.4%) was treated with adjuvant intent. All
      patients were postmenopausal and complained of moderate to severe pelvic pain,
      which resolved after 1-11 months with conservative therapy in all patients. Two
      of these patients also had radiation proctitis. CONCLUSION: In women who present
      with pelvic pain after radiotherapy for cervical cancer, bony destruction and
      fractures may be indicative of a late radiation effect rather than osseous
      metastasis. IF are more common in the curative treatment group than in the
      postoperative adjuvant group.

PMID- 12217747
TI  - The impact of positive peritoneal washings and serosal and adnexal involvement on
      survival in patients with stage IIIA uterine cancer.
AB  - OBJECTIVE: The aim of this study was to determine the prognostic significance of
      serosal involvement (SER), adnexal involvement (ADN), and positive peritoneal
      washings (PPW) in patients with Stage IIIA uterine cancer. We also sought to
      determine patterns of recurrence in patients with this disease. METHODS: The
      records of 136 patients with Stage IIIA uterine cancer treated at the Queensland
      Centre for Gynecological Cancer between March 1983 and August 2001 were reviewed.
      One hundred thirty-six patients underwent surgery and 58 (42.6%) had full
      surgical staging. Seventy-five patients (55.2%) had external beam radiotherapy
      and/or brachytherapy postoperatively. Overall survival was the primary
      statistical endpoint. Statistical analysis included univariate and multivariate
      Cox models. RESULTS: Forty-six patients (33.8%) had adnexal involvement, 23
      (16.9%) had serosal involvement, and 40 (29.4%) had positive peritoneal washings.
      Median follow-up was 55.1 months (95% confidence interval, 36.9 to 73.4 months)
      after which time 71 patients (52.2%) remained alive. For patients with
      endometrioid adenocarcinoma, ADN and SER were associated with impaired survival
      on multivariate analysis (odds ratio 2.8 and 3.2, respectively). In the subgroup
      of patients with high-risk tumors (including papillary serous carcinomas, clear
      cell carcinomas, and uterine sarcomas), neither ADN, nor SER, nor PPW influenced
      survival. CONCLUSION: Patients with Stage IIIA uterine cancer constitute a
      heterogeneous group. For patients with endometrioid adenocarcinoma, both ADN and
      SER, but not PPW, were associated with impaired prognosis. For patients with high
      risk histological types, prognosis is poor for all three factors.

PMID- 12217748
TI  - Age contrasts in clinical characteristics and pattern of care in patients with
      epithelial ovarian cancer.
AB  - OBJECTIVE: The objective of this study was to document and highlight aspects of
      ovarian cancer treatment that pertain, especially, to elderly women. METHODS:
      Data were collected retrospectively from all epithelial ovarian cancer patients
      who were diagnosed in the Gynecologic Oncology Unit at Meir Hospital, Kfar-Saba,
      Israel, from January 1994 to December 1998. RESULTS: The study group comprised
      143 patients (<70 years n = 97, > or =70 years n = 46). Both groups presented
      with the same distribution of stages. The elderly group had fewer primary
      debulking surgical interventions (54.3%) than the younger group (84.5%) (P =
      0.001)). Age was not a limiting factor in achieving optimal debulking in those
      patients who did undergo surgery (older 53%, younger 54%). Almost 92% of the
      younger patients entered a first-line chemotherapy regimen compared to 65.2% of
      the older patients (P = 0.001). The elderly patients were more likely to receive
      neoadjuvant chemotherapy (43.3.3% vs 13.4%, P < 0.01) and hematological toxicity
      was significantly more common (75% vs 36.3%; P = 0.001), although no significant
      difference was noted between the groups in Grade 3-4 patients (> or =70 years,
      62.5% vs <70 years, 45.5%; P = 0.2). The elderly patients were more likely to
      have dose reductions and treatment delays compared to the younger patients (60%
      vs 22.4%; P < 0.001, and 46.6% vs 19.1%; P = 0.004, respectively) and they had
      similar overall response rates (RR) and complete response (80% vs 87.6% and 60%
      vs 71.9%, respectively). CONCLUSIONS: Older women who present with the same
      distribution of stages as their younger counterparts are likely to be treated
      more conservatively than younger ovarian cancer patients. In this study, however,
      when surgery was performed, the optimal tumor debulking rates were similar in
      each group. Although high morbidity, most often hematological toxicity, occurs in
      elderly patients following chemotherapy, the overall RR compared favorably with
      that of younger patients.

PMID- 12217749
TI  - Malignant ascites fluid (MAF), including ovarian-cancer-associated MAF, contains
      angiostatin and other factor(s) which inhibit angiogenesis.
AB  - OBJECTIVE: The aim was to determine whether human malignant ascites fluid (MAF)
      associated with abdominal cancer, including ovarian cancer, contained factors
      which inhibit angiogenesis as well as others which stimulate this process.
      METHODS: MAF was collected from six patients, four with ovarian cancer, one with
      gastric cancer, and one with liver metastases. Using the chick chorioallantoic
      membrane (CAM) the effect of MAF on 7-day-old CAM capillaries was examined for 48
      h. Vascular endothelial growth factor (VEGF) was evaluated by ELISA. Five samples
      of MAF were fractionated by lysine-Sepharose chromatography and the lysine-bound
      and -unbound fractions were eluted by epsilon-amino-n-hexanoic acid. Whole MAF,
      the lysine-bound and -unbound fractions, and human angiostatin were subjected to
      SDS-PAGE/Western blot analysis and immunostained after exposure to anti-human
      plasminogen. Human plasminogen was exposed to conditioned medium from ovarian
      epithelial cancer (HEY) cells and subjected to similar Western blot analysis.
      RESULTS: Despite containing VEGF, each MAF sample examined caused a loss of
      capillaries from the CAM; a similar response was seen using purified human
      angiostatin. Whole MAF and the lysine-bound fraction contained plasminogen (90
      kDa) and a 55-kDa protein which migrated in a similar manner to human angiostatin
      on Western blot. Both the lysine-bound and -unbound fractions caused a loss of
      capillaries in the CAM. Human plasminogen exposed to conditioned medium from HEY
      cells yielded a fragment which was similar in size to angiostatin. CONCLUSIONS:
      MAF from patients with various clinical presentations contains angiostatin and
      VEGF as well as other factors which are capable of inhibiting angiogenesis.

PMID- 12217750
TI  - Bax, Bcl-2, and p53 expression in endometrial cancer.
AB  - BACKGROUND: It has not been fully clarified whether alteration of Bax and other
      apoptosis-relating proteins of Bcl-2 and p53 is involved in endometrial
      carcinogenesis. METHODS: A total of 56 frozen tissues, which included 14 normal
      endometria, 13 endometrial hyperplasias (10 without atypia and 3 with atypia),
      and 29 endometrial carcinomas, were examined for the expression of Bax, Bcl-2,
      and p53 using immunohistochemistry. For Bax-negative cases, PCR-direct sequencing
      was performed for the bax gene. For cases with p53 overexpression, mutational
      analysis was performed for the p53 gene using a yeast functional assay and
      sequencing. RESULTS: Both Bax and Bcl-2 were distinctly expressed in the normal
      proliferative phase endometrium. A decreased Bcl-2/Bax ratio in the secretory
      phase endometrial gland cells due to suppressed Bcl-2 expression was observed.
      Bax expression was positive in all 13 endometrial hyperplasias, while it was
      absent in 6 of 29 endometrial carcinomas (20.7%). Negative Bax expression in
      endometrial carcinoma was not related to tumor stage, histologic subtype, or
      other histopathologic prognostic factors. Bax expression showed no relationship
      to either p53 overexpression or Bcl-2 expression. In the DNA of 6 Bax-negative
      cases, we found a frameshift insertion mutation at codon 58 (AAG to CAAG) in the
      BH3 domain despite the absence of mutation in the (G)8 tract, suggesting that
      this codon may be another preferred target for bax mutation other than the (G)8
      tract. Mutational analysis was available for 7 of 10 cases with p53
      overexpression, in which 5 cases were found to have a missense mutation and 2
      cases had no mutation of the p53 gene. At least 10 of 29 (34.5%) cases of
      endometrial carcinoma were associated with sequence-verified mutation in the bax
      gene and/or p53 gene. CONCLUSIONS: The bax gene frameshift mutation appears to
      cause a loss of Bax expression in endometrial carcinoma. Codon 58 may be a
      preferred target of bax gene mutation in endometrial carcinomas. The bax gene
      mutation seems to occur in the early stage of the genesis of a subset of
      endometrial carcinomas.

PMID- 12217751
TI  - No rules without exception: long-term complete remission observed in a study
      using a LH-RH agonist in platinum-refractory ovarian cancer.
AB  - OBJECTIVE: Second-line chemotherapy in platinum/paclitaxel-resistant ovarian
      cancer induces an objective response in <15% and third-line chemotherapy results
      in responses less than 10%. Chemotherapy always results in side effects with the
      risk of a low quality of life. Endocrine therapy is used world-wide among chemo
      resistant ovarian cancer. Tamoxifen is a standard palliative treatment in many
      centers. LH-RH (luteinizing hormone-releasing hormone) agonists have also
      demonstrated activity among patients with ovarian cancer in several studies with
      response rates of 9-12% and disease stabilization in 15-26% of these women.
      METHODS: In this retrospective study 32 patients with ovarian cancer who had
      relapsed after platinum/paclitaxel-based first-line chemotherapy and had
      exhausted all standard treatments received LH-RH analogue Leuprorelin depot 3.75
      mg sc once a month until tumor progression. RESULTS: One patient (3%) had a
      complete response, with remission time over 3 years. Two patients (6%) reached
      partial response with remission time of 3 and 4 months. Four patients (12%)
      remained stable for a mean time of 7 months (range 4-12 months). The remaining 25
      patients (78%) had progressive disease. The treatment was well tolerated, and no
      major toxicity has been reported. CONCLUSION: This study showed that LH-RH
      agonist Leuprorelin has only a limited effect in patients pretreated with
      platinum-based chemotherapy.

PMID- 12217752
TI  - A phase II study of the MDR inhibitor biricodar (INCEL, VX-710) and paclitaxel in
      women with advanced ovarian cancer refractory to paclitaxel therapy.
AB  - PURPOSE: Incel (biricodar, VX-710) restores drug sensitivity to P-glycoprotein
      (MDR1) and multidrug-resistance-associated protein (MRP1) expressing cells. This
      phase II study evaluated the safety/tolerability, pharmacokinetics, and efficacy
      of VX-710 plus paclitaxel in women with advanced ovarian cancer refractory to
      prior paclitaxel therapy. EXPERIMENTAL DESIGN: Eligible patients had paclitaxel
      refractory disease defined as progressive disease after a minimum of two cycles
      of paclitaxel (weekly or 3-week schedule) or relapsed disease within 4 months of
      prior paclitaxel therapy. Patients received 80 mg/m(2) paclitaxel over 3 h
      starting 4 h after initiation of a 24-h continuous intravenous infusion of 120
      mg/m(2)/h VX-710. Cycles were repeated every 3 weeks. RESULTS: Fifty patients
      received treatment and 45 were evaluable for response. VX-710 + paclitaxel
      therapy was generally well tolerated. Myelosuppression was the principal
      toxicity, with a median Cycle 1 nadir absolute neutrophil count of 0.27 x 10(9)
      cells/L and a 47% overall incidence of Grade 4 neutropenia. Mild to moderate
      peripheral neuritis or neuropathy was the primary nonhematologic toxicity,
      affecting 62% of patients. Other nonhematologic toxicities were generally mild to
      moderate and reversible. Paclitaxel area under the concentration-versus-time
      curve (AUC) (16 +/- 5.3 microg x h/mL) during the first treatment cycle was
      comparable to standard 175 mg/m(2) paclitaxel administered over 3 h. Of the 3
      patients who achieved partial responses, 2 had progressed during prior paclitaxel
      therapy. Twelve patients maintained stable disease and 14/45 (31%) of patients
      had CA-125 reductions of 50-90% for up to 24 weeks. The median time-to-disease
      progression was 10 weeks for the intent-to-treat population and 20.7 weeks for
      the CA-125 responders. CONCLUSIONS: The results suggest that VX-710 with
      paclitaxel has modest activity in paclitaxel-resistant ovarian cancer. Further
      research is warranted in less heavily treated patients.

PMID- 12217753
TI  - Explorative laparoscopy prior to exenterative surgery.
AB  - OBJECTIVE: The objective of this study was to identify the advantages and limits
      of laparoscopy for assessment of eligibility for exenterative procedures in
      patients with gynecologic malignancies. METHODS: Between April 1998 and April
      2001, 41 consecutive patients with primary or recurrent gynecologic malignancy
      underwent explorative laparoscopy to detect eligibility for exenteration.
      RESULTS: Mean age of patients was 54 years (range, 31-80 years). Twenty out of 41
      (48.7%) patients underwent exclusively explorative laparoscopy due to
      unresectable disease or intraabdominal spread of disease. Median operative time
      for this cohort of patients was 69.1 min (range, 10-278), median blood loss was
      30 cc (range 10-60) and no complications occurred. Based on findings of
      explorative laparoscopy 21 out of 41 (51.2%) patients were eligible for
      exenteration. Evaluation of extension of disease was correctly done by
      laparoscopy and was not corrected at laparotomy. One patient out of 21 (4.76%)
      had extension of disease missed at both laparoscopy and laparotomy and discovered
      only at an advanced phase of exenteration. Histology of exenterative specimens
      confirmed laparoscopic evaluation in 20 out of 21 patients (95.25%). CONCLUSIONS:
      Laparoscopy proved effective for evaluation of patients who were candidates for
      exenteration and helped to avoid unnecessary laparotomy in half of the candidate
      patients.

PMID- 12217754
TI  - Comparison of tolerance of combination carboplatin and paclitaxel chemotherapy by
      age in women with ovarian cancer.
AB  - OBJECTIVE: The objective of this study was to compare tolerance of treatment of
      ovarian cancer patients > or = 70 years to those < or =55. MATERIALS AND METHODS:
      A retrospective review of all data relevant to comparison of clinical course in
      31 women > or =70 years (Study Group) and 44 women < or =55 (Control Group), who
      received primary therapy for ovarian cancer between 1996 and 2001 was performed.
      The tolerance of the entire treatment plan was then compared using SAS 8.1 (Gary,
      IN), chi(2) test with Yates correction or Fischer's exact test, and the Student t
      test as appropriate. RESULTS: The mean age for the study group was 73, and for
      the control group 49. Statistically significant differences were as follows: the
      study group had a lower hemoglobin and serum albumin, higher performance status
      postoperatively, and received lower carboplatin dose and dose intensity. The
      groups were similar in stage at presentation, medical comorbidities, estimated
      blood loss, optimal cytoreduction rates, dose intensity of paclitaxel, completed
      number of chemotherapy cycles, time intervals from surgery to completion of
      therapy, and posttreatment performance status and nutritional status. The rate of
      grade 3 and 4 toxicities was low in both groups, and did not hinder delivery of
      therapeutic dose of chemotherapy. CONCLUSION: Women in the study group tolerated
      aggressive cytoreductive surgery and therapeutic doses of chemotherapy, despite
      poorer nutritional status and general health at time of diagnosis. Although older
      women are more likely to have chemotherapy dose reduction, the treatment remained
      within the recommended standard dosage.

PMID- 12217755
TI  - Saline infusion sonography and office hysteroscopy to assess endometrial
      morbidity associated with tamoxifen intake.
AB  - OBJECTIVE: The objective of this study was to compare office feasibility, patient
      acceptance, and diagnostic accuracy of hysteroscopy (HYS) and saline infusion
      sonography (SIS) in breast cancer patients taking tamoxifen. METHODS: Sixty-six
      asymptomatic postmenopausal women on tamoxifen for breast cancer underwent SIS,
      followed by outpatient HYS with endometrial biopsy. In all women an endometrial
      stripe over 4 mm was previously measured by transvaginal ultrasonography (TU).
      Histologic reports were matched with sonographic and hysteroscopic findings.
      After SIS and HYS, patients were asked to rate pelvic pain experienced during the
      two procedures on a 10 cm Visual Analog Scale (VAS). RESULTS: SIS and HYS were
      not accomplished in 26 (39.3%) and 4 (6.0%) patients, respectively, due to
      cervical stenosis or patient intolerance. No adverse event was recorded after 40
      SIS and 62 hysteroscopic procedures. Pathologic assessment reported 15 polyps
      (22.7%), 7 hyperplasias (10.5%), and 2 submucous myomas (3.0%). Sensitivity,
      specificity, and negative and positive predictive values of SIS in distinguishing
      between normal and abnormal endometrium were 85.7, 83.3, 93.7, and 66.0%,
      respectively, whereas HYS provided corresponding values of 100, 94.1, 97.8, and
      100%, respectively. No significant difference was found between SIS and HYS in
      the subjective perception of pelvic pain (VAS scores 3.02 +/- 2.8 and 3.82 +/-
      2.7, respectively). CONCLUSIONS: Office hysteroscopy is a safe and conclusive
      diagnostic tool for endometrial investigation in menopausal women on tamoxifen.
      It exposes the patients to the same pelvic discomfort as SIS, but has a better
      feasibility rate and diagnostic accuracy.

PMID- 12217756
TI  - Detection of tumor circulating cells by cytokeratin-20 in the blood of patients
      with granulosa cell tumors.
AB  - OBJECTIVE: Cytokeratins (CKs) are constituents of the intermediate filaments of
      epithelial cells which are expressed in various combinations, depending on the
      epithelial type and the degree of differentiation. Using the reverse
      transcriptase-polymerase chain reaction (RT-PCR) technique, we recently
      demonstrated that cytokeratin-20 (CK-20), the most recently discovered
      cytokeratin, is expressed in endometrial carcinoma tumors, in blood, and in lymph
      nodes with micrometastases of patients treated for endometrial carcinomas.
      However, CK-20 expression could not be demonstrated in the endometrium of
      patients with benign diseases, in peripheral blood, in lymph nodes of healthy
      subjects, or in normal blood cells. The aim of this study was to examine whether
      CK-20 expression in blood can be used as a biomarker for the detection of the
      dissemination of malignant cells in patients treated for granulosa cell tumors
      (GCTs). METHODS: In this study, we used RT-PCR to determine the expression of CK
      20 in the following groups: (i) blood of patients (n = 14) treated for GCTs, (ii)
      GCT samples (n = 4); (iii) lymph nodes (n = 2) of patients treated for GCTs; (iv)
      blood from subjects with benign sex-cord-stromal tumors (n = 2); (v) normal
      ovaries of two menstruating women (n = 4); (vi) tumor specimens of epithelial
      ovarian carcinomas (EOCs) (n = 14); and (vii) blood samples (n = 18) and lymph
      nodes (n = 11) of healthy women. RESULTS: In Group I, CK-20 was positive in the
      blood in 86% (12/14) of the patients. In Group II, CK-20 was positive in 100%
      (4/4) of the GCT samples. In Group III, CK-20 was positive in 100% (2/2) of the
      lymph nodes examined. In Groups IV and V, CK-20 was negative in 100% (2/2) of the
      blood samples and in the normal ovarian specimens (4/4) that were examined. In
      Group VI, CK-20 was positive in 14% (2/14) of nonmucinous EOCs. In Group VII, CK
      20 was negative in 100% (18/18) of blood and in (11/11) lymph node specimens
      (specificity 100%). CONCLUSIONS: These results indicate that RT-PCR of CK-20,
      because of its high sensitivity and specificity, is a potential biomarker for
      detecting metastases in blood and in micrometastases in lymph nodes of patients
      treated for GCTs.

PMID- 12217757
TI  - Shortcomings and deficits in surgical treatment of gynecological cancers: a
      German problem only?
AB  - OBJECTIVES: The objective of this study was to assess the quality of preoperative
      diagnostic, primary surgical, and postoperative treatment of ovarian,
      endometrial, and cervical cancers in women in Hesse, Germany, in relation to
      current international recommendations. METHODS: Data on all diagnostic, surgical,
      and postoperative gynecological procedures undertaken in Hesse in 1997-2001 were
      collected in a standardized form and validated for clinical quality. Databases
      were generated for cases of endometrial, ovarian, and cervical cancer, and
      details of treatment were analyzed. RESULTS: There were 1119 cases of
      endometrial, 824 cases of ovarian, and 472 cases of cervical cancer. The
      malignancy remained undiagnosed until after surgery in 17.8% (199/1119) of
      endometrial cancers, 28.5% (245/824) of ovarian cancers, and 15.5% (73/472) of
      cervical cancers. There was evidence of suboptimal surgical treatment.
      Lymphadenectomy rates were low in endometrial and ovarian cancers (about 32%),
      and omentectomy rates in were low in ovarian cancer (about 50%). Furthermore,
      10.7% (31/289) of patients with cervical cancer diagnosed before hospital
      admission did not undergo radical surgery. CONCLUSION: Discrepancies between
      guidelines and treatment of gynecological cancers in Hesse were striking,
      particularly for endometrial and ovarian cancer, and this situation may be
      mirrored internationally. The fact that many guidelines are not supported by
      results from clinical studies may be a factor in this apparently suboptimal
      treatment. Clinical collaborative trials are needed to provide the necessary
      evidence to support current recommendations and benchmarks of survey are required
      to facilitate future quality assessment.

PMID- 12217758
TI  - Treatment of uterine leiomyosarcoma in a xenograft nude mouse model using high
      intensity focused ultrasound: a potential treatment modality for recurrent pelvic
      disease.
AB  - OBJECTIVE: The objective was to test the efficacy of high-intensity focused
      ultrasound (HIFU) for treatment of uterine leiomyosarcoma in a Xenograft nude
      mouse model. METHODS: A total of 65 athymic nude mice were inoculated
      subcutaneously with 5 to 7 x 10(6) ELT-5B cells, a uterine leiomyosarcoma cell
      line derived from the Eker rat. Thirty animals showed tumor growth. The tumor
      volume was measured transcutaneously once a week. Animals were randomly assigned
      to three groups: HIFU treatment (n = 17), sham treatment (n = 7), and control (n
      = 6). A HIFU device, operating at a frequency of 2.0 MHz and an intensity of 2000
      W/cm(2), was used for treatment. RESULTS: Within 3 weeks of a single HIFU
      treatment, 100% reduction in tumor volume was observed in all animals, except
      one. A second HIFU treatment was applied to that animal, resulting in 100%
      reduction in tumor volume. The tumors in the sham-treated animals continued to
      grow at a similar rate to that of the control group to approximately 500% of the
      tumor volume at the time of treatment. All animals were monitored for a maximum
      of 3 months. No metastasis was observed in the HIFU-treated animals. Histological
      examination confirmed a complete tumor disappearance after HIFU treatment.
      CONCLUSION: We have shown that HIFU can effectively treat uterine leiomyosarcoma
      tumors inoculated in Xenograft nude mice, demonstrating HIFU's potential use for
      treatment of recurrent uterine leiomyosarcoma.

PMID- 12217759
TI  - Modified technique for urinary diversion with incontinent conduits.
AB  - BACKGROUND: Incontinent urinary diversions are frequently performed in
      gynecologic oncology. The incontinent urinary diversions generally utilize a
      short segment of distal ileum or colon as a conduit. Conduit complications such
      as anastomosis leaks and strictures may be related to the technique utilized for
      inserting and securing the ureters and the degree of postimplant manipulation.
      TECHNIQUE: We describe a technique using a metal Yankaur suction device placed
      through the conduit's matured stoma to facilitate the mucosa-to-mucosa
      anastomosis of the ureters. This procedure allows for tension-free ureteral
      anastomoses, the isolation of the ideal conduit length, optimal stomal
      maturation, and reduced manipulation of the conduit after the ureteral
      anastomoses. CONCLUSION: This modification provides an elegant, yet simple and
      expedient, method of ureteral anastomosis to the incontinent urinary conduit.

PMID- 12217760
TI  - Does the interval from primary surgery to chemotherapy influence progression-free
      survival in ovarian cancer?
AB  - OBJECTIVES: The objective of this study was to determine whether the length of
      the interval from primary surgery to commencement of chemotherapy has any direct
      effect on progression-free survival in ovarian cancer. METHODS: The progression
      free survival of 472 patients enrolled in four trials who had all received
      platinum-containing chemotherapy (either in combination with a taxane or
      cyclophospamide) was subjected to univariate analysis. Dividing subjects into
      those above and below the median interval from surgery to chemotherapy formed two
      groups for analysis. The analysis was stratified by study and arm/cohort within
      study to remove any possible influence of the different studies and study doses.
      Multivariate analysis was then performed including stage, bulk of residual
      disease, and performance status as well as interval to starting chemotherapy.
      RESULTS: The median interval from surgery to chemotherapy was 22 days (range 7
      100). Univariate analysis of the above median and below median groups showed
      worse progression-free survival for those with earlier treatment (hazard ratio
      0.84, P = 0.14, 95% CI 0.67-1.06); however, those treated earlier tended to have
      bulkier residual disease (>2 cm; P = 0.006). When multivariate analysis was
      performed incorporating residual disease status, FIGO stage, and performance
      status, the hazard rate ratio for interval to surgery was 0.99 (P = 0.91, 95% CI
      0.79-1.24). CONCLUSIONS: This study suggests that the interval from surgery to
      commencement of chemotherapy is not an independent prognostic factor for
      progression-free survival.

PMID- 12217761
TI  - Sentinel node metastasis in the groin detected by technetium-labeled nannocolloid
      in a patient with cervical cancer.
AB  - OBJECTIVE: The aim of this study was to describe the first sentinel groin node
      metastasis detected by technetium-labeled nanocolloid in a patient with cervical
      carcinoma. METHOD: Preoperatively, 60 mBq technetium-labeled nannocolloid was
      injected at 3 and 9 o'clock in the uterine cervix. Sentinel nodes were detected
      using a handheld and laparoscopic probe (Navigator) and removed for pathological
      assessment. RESULTS: A 52-year-old diagnosed with FIGO stage IIA squamous
      cervical carcinoma was referred to our unit. On physical examination a bulky
      cervical tumor and a 1.5-cm enlarged left inguinal lymph node were found. No
      other abnormalities were seen on pelvic MRI scan and CT scan of the abdomen and
      lower pelvis. Preoperative lymphoscintigraphy showed that a left groin node and
      three nodes located in the right obturator fossa were the sentinel nodes. They
      were easily detected using, respectively, a hand-held and a laparoscopic probe
      and removed. As both the inguinal and the obturator lymph nodes contained
      metastatic deposits, the patient was treated with the combination of chemotherapy
      and radiotherapy. CONCLUSION: Inguinal lymph nodes can rarely be the sentinel
      nodes in patients with cancer of the uterine cervix.

PMID- 12217762
TI  - Further study of the management of cervical adenocarcinoma in situ.
AB  - OBJECTIVE: The objective of this study was to study further the management of
      cervical adenocarcinoma in situ (AIS) with particular regard to the results of
      conservative management without hysterectomy and the use of large loop excision
      of the transformation zone (LLETZ). METHODS: Based upon the files of the
      Pathology Department at the Cleveland Clinic Foundation, recently encountered AIS
      patients were combined with patients from a previous study that ended in 1994.
      Charts and clinical materials were retrospectively reviewed and abstracted.
      RESULTS: Fifty-two patients were identified for a combined study group of 98
      patients. The mean age was 37 years. Fifty-two percent were identified due to
      abnormal squamous elements on a Pap smear and 43% due to abnormal glandular
      cells. In patients treated with hysterectomy, 67% were found to have residual
      disease following conization with positive margins including 3 patients with
      invasive cancer. Among all patients, LLETZ was associated with a positive margin
      rate of 57.1% vs 27.3% with cold knife conization (CKC) (chi(2), P = 0.008).
      Among patients treated conservatively with conization, the rates of positive
      margins were 40.0 and 20.0%, respectively, for LLETZ and CKC (chi(2), P = 0.11);
      9.5% of conservatively managed patients with negative initial conization margins
      eventually had recurrent AIS. CONCLUSION: Cold knife conization is the preferred
      method of management for cervical AIS patients selecting conservative treatment.
      Despite initial conization margins being uninvolved, such patients have an
      approximate risk of 10% for recurrent AIS.

PMID- 12217763
TI  - Adenocarcinoma in situ of the cervix: a prospective study of conization as
      definitive treatment.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of
      combination laser conization alone as definitive treatment of adenocarcinoma in
      situ (AIS) and to evaluate the safety of a conservative expectant strategy
      irrespective of cone margin status. METHODS: Sixty consecutive patients with
      histologically proven adenocarcinoma in situ were treated with combination laser
      conization from 1990 to April 2001. In 58 cases this was considered final
      therapy, and patients were followed for a mean period of 49 months. RESULTS: The
      mean age was 34.9 years. Preconization evaluation demonstrated AIS in 76.7%. In
      58 cases conization was considered final therapy, and in these cone margins were
      involved in 15 cases. Twenty-seven patients (46.6%) were followed for more than
      60 months. Totally, 4 recurrences (6.9%) were observed. One recurrence was
      observed in patients with involved margins (6.7%) 4 months after conization, and
      3 recurrences in patients with uninvolved margins (6.9%) were registered, in 2
      cases more than 5 years after conization. No case of invasive disease was
      diagnosed during follow-up. The mean cone height was 19 mm; 16.7% of the cone
      biopsies were more than 25 mm. CONCLUSIONS: Combination laser conization was an
      effective treatment of AIS, and an expectant follow-up schedule based on cytology
      was demonstrated to be safe irrespective of cone margin status after a
      significant follow-up period. A potential risk of overtreatment and unnecessary
      worrying of the patients exists if further treatment is based solely on the
      status of the cone margins. Only prospective studies of similar strategies will
      give sufficient evidence for valid recommendations concerning the management of
      AIS.

PMID- 12217764
TI  - Chylous ascites following treatment for gynecologic malignancies.
AB  - BACKGROUND: Chylous ascites is a rare complication following abdominal radiation
      or para-aortic lymph node dissection in the management of gynecologic
      malignancies. Treatment options include dietary restriction with addition of
      medium-chain triglycerides, serial paracenteses, total parenteral nutrition, and
      somatostatin. Current opinion advocates that surgical exploration and peritoneo
      venous shunts be reserved for refractory cases. CASES: Two patients developed
      chylous ascites, one after completion of surgical staging and chemoradiation for
      stage IIB squamous carcinoma of the cervix and one following para-aortic lymph
      node dissection for recurrent malignant mixed mullerian tumor of the endometrium.
      In both cases resolution of the chylous ascites followed placement of a peritoneo
      venous shunt. CONCLUSIONS: Chylous ascites should be considered in the
      differential diagnosis of ascites in patients with gynecologic malignancy treated
      with radiation or para-aortic lymph node dissection.

PMID- 12217765
TI  - BRCA1-related malignancies in a family presenting with von Recklinghausen's
      disease.
AB  - BACKGROUND: The association between neurofibromatosis and gynecologic
      malignancies is rarely reported in the literature. Both BRCA1 and NF1 genes are
      located on the long arm of chromosome 17. CASE: We have observed a pedigree
      showing several individuals affected by both type 1 neurofibromatosis (NF1) and
      breast or coelomatic cancers. The number of individuals affected, their degree of
      relationship, and the early age at onset were suggestive of an hereditary
      breast/ovarian cancer syndrome. Linkage analysis was performed in order to
      establish whether markers in the chromosome 17 region containing the BRCA1 and
      NF1 loci were shared by affected individuals. Screening for BRCA1 mutations was
      performed by PTT and SSCP. Analysis of chromosome 17 DNA markers in the five
      family members tested show that three individuals affected by both NF1 and
      carcinomas share a common haplotype including the NF1 and BRCA1 loci on
      chromosome 17. Mutation analysis showed the presence of a nonsense mutation
      within BRCA1 exon 12 in two individuals, mother and daughter, affected by breast
      and peritoneal cancer, respectively, as well as in the son, who had rectal cancer
      at the early age of 27 years. All three subjects also had NF1. CONCLUSION: The
      concurrence of NF1 and hereditary breast/ovarian cancer in this family is likely
      due to the presence of two linked mutations at the NF1 and BRCA1 loci.

PMID- 12217766
TI  - Parafallopian tube transitional cell carcinoma.
AB  - BACKGROUND: Transitional cell carcinoma (TCC) has recently been acknowledged as a
      distinct histologic pattern of the uncommon primary fallopian tube carcinoma.
      However, rare cases of TCC that are closely associated to the extraluminal
      portion of the tube remain widely unrecognized. CASE: We present a left adnexal
      high-grade TCC in a 56-year-old postmenopausal woman with an elevated serum CA
      125 level. The tumor was attached by a small stalk to the serosal surface of the
      left fallopian tube and was completely separate from the uninvolved uterus and
      ipsilateral ovary. Histologic examination of the tubal lumen epithelium revealed
      neither atypia nor involvement by the neoplasm. Immunohistochemistry showed the
      tumor cells to be positive for pankeratin, calretinin, progesterone and estrogen
      receptors, and cytokeratin 7, and negative for cytokeratin 20, consistent with a
      Mullerian derivation. CONCLUSION: Our case represents the fourth reported
      instance of a primary paratubal TCC. Perhaps, this entity falls under a
      previously unrecognized category of carcinomas that collectively may arise from
      Walthard's rest, paratubal cyst, or directly from the tubal serosa.

PMID- 12217767
TI  - Primary extranodal marginal zone B-cell lymphoma of the fallopian tube.
AB  - BACKGROUND: Only 2% of all extranodal primary lymphomas affect the female genital
      tract. Involvement of the fallopian tubes by primary lymphoma is extremely rare.
      CASE: A 34-year-old patient presented with the symptoms of salpingitis.
      Laparoscopy with salpingectomy was performed. Salpingitis caused by Acinetobacter
      species was diagnosed and antibiotic treatment was administered. Histologic
      examination of the fallopian tube revealed primary extranodal marginal zone B
      cell lymphoma (MALT-type lymphoma) of the fallopian tube. After 12 months no
      tumoral recurrence occurred. CONCLUSION: Although the female genital tract is
      rich in mucosa and the existence of mucosa-associated lymphoid tissue (MALT) has
      been demonstrated previously, extranodal marginal zone B-cell lymphoma of the
      fallopian tube is exceptional. To our knowledge only two cases with extranodal
      marginal zone B-cell lymphoma of the fallopian tube have been previously
      reported. Existence of inflammation close to the tumor is interesting to
      emphasize.

PMID- 12217768
TI  - The evaluation of the sentinel node successfully conducted in a case of malignant
      melanoma of the vagina.
AB  - BACKGROUND: The sentinel node biopsy has been established as a standard procedure
      in many types of cancer. To date, only one case was reported for successful
      detection of the sentinel node using a radiopharmaceutical-directed mapping
      technique in malignant melanoma of the vagina. CASE: An 81-year-old woman
      developed malignant melanoma arising from the lower third of the vagina. She
      underwent local resection of the tumor and exploration of the sentinel node using
      blue dye. The sentinel node was detected successfully in the groin, and was
      negative for metastasis. Intra-cavity irradiation was given as an adjuvant
      therapy. CONCLUSION: In view of relative ease and minimal trauma, sentinel node
      mapping could be a routine procedure in malignant melanoma arising from the
      vagina or vulva.

PMID- 12217769
TI  - The role of tamoxifen in the management of ovarian cancer.

PMID- 12217771
TI  - You are what you eat.

PMID- 12217772
TI  - Huntington's disease provides cancer clues.

PMID- 12217773
TI  - Aspirin may lower risk of pancreatic cancer.

PMID- 12217775
TI  - 3D conformal radiotherapy is safer than a brachytherapy-external-beam
      combination.

PMID- 12217776
TI  - Endostatin imaging to help understanding of antiangiogenic drugs.

PMID- 12217777
TI  - Morphine stimulates tumour growth.

PMID- 12217779
TI  - Gutkha banned in Indian states.

PMID- 12217778
TI  - New targets identified for preventing cognitive decline after cranial
      irradiation.

PMID- 12217780
TI  - Urine test for bladder cancer.

PMID- 12217781
TI  - Survivors of lung cancer have good quality of life.

PMID- 12217782
TI  - Vaccination with varicella protects against zoster infection.

PMID- 12217783
TI  - Promising results in stomach cancer trial.

PMID- 12217784
TI  - 3-Bromopyruvate kills cancer cells in animals.

PMID- 12217785
TI  - How good is cost-benefit assessment of phase II cancer trials?

PMID- 12217786
TI  - Overhauling the breast cancer overview: are subsets subversive?

PMID- 12217787
TI  - Changes needed for improved cancer care in the developing world.

PMID- 12217788
TI  - Erythropoietin improves quality of life--a response.

PMID- 12217789
TI  - Thyroid cancer in a child born after the Chernobyl disaster.

PMID- 12217790
TI  - Part I: chemotherapy for epithelial ovarian cancer-treatment at first diagnosis.
AB  - Ovarian cancer leads to more deaths than any other gynaecological cancer in the
      more developed countries. During the past 30 years, survival has increased owing
      to improvements in diagnosis, surgery, and chemotherapy. Despite these advances,
      most patients will die from the disease, and the overall 5-year survival is less
      than 50%. Most patients with ovarian cancer need cytotoxic chemotherapy. Platinum
      agents (cisplatin and carboplatin) are the most important drugs to be included in
      first-line regimens. Randomised trials have recently confirmed the benefit of the
      addition of taxanes to platinum, and the standard of care has become the
      combination of carboplatin and paclitaxel. However, unanswered questions remain
      over the optimum schedule, duration, and intensity of treatment, and the benefit
      or otherwise of the addition of other drugs to carboplatin and paclitaxel. The
      roles of intraperitoneal therapy and consolidation treatment after first-line
      chemotherapy are as yet undefined.

PMID- 12217791
TI  - Part II: chemotherapy for epithelial ovarian cancer-treatment of recurrent
      disease.
AB  - For women with advanced ovarian cancer, rates of response to first-line
      chemotherapy are high but most patients have relapses and become candidates for
      further chemotherapy. Chemotherapy for recurrence can palliate symptoms, and
      there is some evidence that it can also improve survival in this clinical
      situation. Patients who relapse quickly after first-line therapy should not be
      given the same drugs as were used initially. However, for patients who have
      longer intervals from treatment to relapse, the rates of response to a
      rechallenge with platinum are clinically significant. Several cytotoxic drugs
      have shown activity in patients whose disease has relapsed after therapy with
      platinum and a taxane; these drugs include topotecan, etoposide, pegylated
      liposomal doxorubicin, epirubicin, gemcitabine, altretamine, oxali platin, and
      vinorelbine. Recurrent ovarian cancer is also an important setting in which to
      test investigational agents with promising activity, such as new platinum
      compounds, new taxanes, and other cytotoxic agents, as well as non-cytotoxic
      compounds with novel mechanisms of action.

PMID- 12217792
TI  - Green fluorescent protein imaging of tumour growth, metastasis, and angiogenesis
      in mouse models.
AB  - We have developed a way of imaging metastases in mice by use of tumour cells
      expressing green fluorescent protein (GFP) that can be used to examine fresh
      tissue, both in situ and externally. These mice present many new possibilities
      for research including real-time studies of tumour progression, metastasis, and
      drug-response evaluations. We have now also introduced the GFP gene, cloned from
      bioluminescent organisms, into a series of human and rodent cancer-cell lines in
      vitro, which stably express GFP after transplantation to rodents with metastatic
      cancer. Techniques were also developed for transduction of tumours by GFP in
      vivo. With this fluorescent tool, single cells from tumours and metastases can be
      imaged. GFP-expressing tumours of the colon, prostate, breast, brain, liver,
      lymph nodes, lung, pancreas, bone, and other organs have also been visualised
      externally by use of quantitative transcutaneous whole-body fluorescence imaging.
      GFP technology has also been used for real-time imaging and quantification of
      angiogenesis.

PMID- 12217793
TI  - Poor-prognosis high-grade gliomas: evolving an evidence-based standard of care.
AB  - Patients with high-grade glioma (HGG) can be classified as having a favourable
      prognosis (younger or with good performance status) or a poor prognosis (older or
      with poor performance status) with median survival of 12-24 months and 6-9
      months, respectively. The standard management for the favourable subgroup is
      maximum safe resection followed by adjuvant conventionally fractionated radio
      therapy, with or without chemotherapy. However, most patients with HGG have a
      poor prognosis and their optimum management has yet to be defined. In the poor
      prognosis HGG subgroup, short-course radiotherapy is equivalent to conventional
      radiotherapy in terms of survival and palliation (level II evidence), but
      chemotherapy is not recommend ed (level II evidence). The problems with the
      existing systems of prognosis are discussed and a pragmatic system proposed.
      Owing to lack of any level I evidence, the need to conduct prospective randomised
      trials with quality of life and palliative effect as primary endpoints is
      emphasised. Until such time, maximum safe resection followed by a short course of
      focal radiotherapy is recommended as the standard of care in poor prognosis HGG.

PMID- 12217794
TI  - Overweight, obesity, and cancer risk.
AB  - Over the past few decades the proportion of people with excess body weight has
      been increasing in both developed and less developed countries. About 50% of men
      and 35% of women in Europe are currently estimated to be overweight or obese. In
      addition to an increase in the risk of cardiovascular disease and type II
      diabetes, the evidence summarised here shows that excess body weight is directly
      associated with risk of cancer at several organ sites, including colon, breast
      (in postmenopausal women), endometrium, oesophagus, and kidney. In part, these
      associations with cancer risk may be explained by alterations in the metabolism
      of endogenous hormones-including sex steroids, insulin, and insulin-like growth
      factors-which can lead to distortion of the normal balance between cell
      proliferation, differentiation, and apoptosis. Avoidance of weight gain thus
      seems to be an important factor for cancer prevention.

PMID- 12217795
TI  - Natural Killer T cells.

PMID- 12217796
TI  - The price of anticancer intervention. Treatment-induced malignancy.

PMID- 12217797
TI  - What is clinical research for?

PMID- 12217798
TI  - Five (un)easy pieces: the MYH9-related giant platelet syndromes.

PMID- 12217799
TI  - Imatinib: can one outwit chronic myeloid leukemia?

PMID- 12217800
TI  - Inside haematologica: the impact of age on the outcome of allogeneic stem cell
      transplantation.

PMID- 12217801
TI  - Fas signaling and blockade of Bcr-Abl kinase induce apoptotic Hrk protein via
      DREAM inhibition in human leukemia cells.
AB  - BACKGROUND AND OBJECTIVES: The apoptotic Bcl-2 family member Hrk is
      transcriptionally silenced via DREAM in hematopoietic progenitor cell lines, and
      is specifically induced after growth factor withdrawal. Given that expression of
      Hrk is sufficient to induce apoptosis, we studied the expression of this
      apoptotic protein and its regulatory mechanism in human leukemia cells. DESIGN
      AND METHODS: K562 chronic myeloid leukemia cells were treated with STI571, a Bcr
      Abl kinase inhibitor, and the Jurkat T-cell leukemia cell line was incubated with
      agonistic anti-Fas antibodies. Following treatment, we correlated the expression
      of Hrk protein with the DNA binding capacity of DREAM, and the induction of
      apoptosis. RESULTS: We show that treatment of K562 with STI571 blocks the binding
      of DREAM to the Hrk gene and allows the expression of Hrk, which correlates with
      the induction of apoptosis. Similarly, treatment of Jurkat cells with agonistic
      anti-Fas antibodies triggers the expression of Hrk through DREAM inactivation.
      Interestingly, inhibition of caspases, by culturing Jurkat cells in the presence
      of z-VAD-fmk, abrogates Fas-mediated hrk expression and apoptosis. Furthermore,
      in vitro analysis shows that active recombinant caspase-3 releases a fragment
      from the DREAM protein, suggesting that caspase-3 may be upstream of DREAM.
      INTERPRETATION AND CONCLUSIONS: These data suggest that apoptosis inducers as
      diverse as oncoprotein inhibitors and cell death receptor activators trigger Hrk
      expression via blockade of DREAM in leukemia cells, and this apoptotic pathway
      may be regulated, at least in some systems, by the proteolytic activity of
      caspase-3.

PMID- 12217802
TI  - Bcl-6 p53 mutations in lymphomas carrying the bcl-2/Jh rearrangement.
AB  - BACKGROUND AND OBJECTIVES: The t(14;18)(q32;q21) chromosomal translocation is the
      hallmark of follicular lymphomas (FL). The translocation induces the
      overexpression of the Bcl-2 protein and prolongs the survival of clonogenic
      cells. Tumor cells may acquire additional molecular alterations that may be
      associated with histologic progression or with chemo-resistance. DESIGN AND
      METHODS: We analyzed the distribution and association of bcl-6 and p53 mutations
      in 55 consecutive bcl-2/Jh+ lymphoma samples derived from 43 patients obtained at
      the time of diagnosis and, in 5 of these patients, during follow-up. A total of
      29 bcl-6 point mutations were detected in seventeen patients (40%) associated
      with major or minor breakpoints of the bcl-2/Jh fusion gene. In seven cases a p53
      mutation was detected. Three cases corresponded to FL with the minor breakpoint
      in the bcl-2 gene and these patients had a favorable clinical evolution, whereas
      the 4 patients with p53 mutations and the major breakpoint had a bad clinical
      outcome with morphologic transformation to high-grade lymphoma in three cases.
      The sequential analysis of 5 patients showed a different timing in the
      acquisition of mutations: one patient showed bcl-6 and p53 mutations at
      diagnosis, another patient showed bcl-6 mutations at diagnosis and acquired a p53
      mutation later whereas the third patient had a p53 mutation before the appearance
      of the bcl-6 mutation. RESULTS: We did not find significant differences in
      survival between patients with FL who showed exclusively bcl-6 mutations and
      those without bcl-6 mutations, but those patients with a high International
      Progostic Index score and p53 mutations showed the lowest overall survival (p =
      0.002). INTERPRETATION AND CONCLUSIONS: These findings suggest that bcl-2/Jh
      lymphomas show molecular heterogeneity and that bcl-6 and p53 mutations may be
      acquired during the evolution of such lymphomas. Bcl-6 mutations, by themselves,
      do not seem to be associated with a bad prognosis. Rearrangements at the minor
      bcl-2 locus may have a different molecular evolution.

PMID- 12217803
TI  - Rituximab reduces the number of peripheral blood B-cells in vitro mainly by
      effector cell-mediated mechanisms.
AB  - BACKGROUND AND OBJECTIVES: The humanized CD20 mono- clonal antibody, rituximab,
      has significant anti-tumor activity in patients with B-cell non-Hodgkin's
      lymphoma and induces depletion of B-cells in vivo. It was the objective of this
      study to define the contribution of the different mechanisms of action of
      rituximab on primary normal and malignant B-cells. DESIGN AND METHODS: Primary
      human B-lymphocytes and effector cell fractions were isolated from peripheral
      blood of normal donors using an immunomagnetic separation technique. Blood
      samples from 20 patients with chronic lymphocytic leukemia (CLL) were studied and
      the B-lymphoblastoid Daudi cell line was used as a control. B-cells were cultured
      in the presence or absence of rituximab adding a secondary hyper-crosslinking
      antibody, serum as source of complement or different effector cell fractions. The
      cells were analyzed by immunofluorescence staining and flow cytometry. RESULTS:
      In contrast to the B-lymphoblastoid Daudi cell line, the number of highly
      purified normal peripheral blood CD19+ cells was only minimally affected by
      rituximab in the presence of autologous serum. A significant reduction in the
      number of B-cells was observed when mononuclear cells from peripheral blood were
      added back. To identify the cell type which mediates this effect, CD3+ T-cells,
      CD56+ cells, and CD14+ monocytes were added to selected CD22+ B-cells. A marked B
      cell decrease was only observed in the presence of CD56+ and CD14+ cells in an
      effector to target ratio of 10:1. The experiments with mononuclear cells from
      patients with CLL showed a B-cell reduction by rituximab, which was significantly
      enhanced following addition of granulocyte-macrophage colony-stimulating factor
      (GM-CSF). INTERPRETATION AND CONCLUSIONS: These data support the important role
      of cell-mediated mechanisms in the B-cell-depleting action of rituximab and
      suggest that pre-treatment with GM-CSF could improve the response to rituximab in
      patients with CLL.

PMID- 12217804
TI  - Fludarabine, ara-C, novantrone and dexamethasone (FAND) in previously treated
      chronic lymphocytic leukemia patients.
AB  - BACKGROUND AND OBJECTIVES: The objective of improving the quality of responses of
      chronic lymphocytic leukemia (CLL) patients has led to the design of protocols
      that combine fludarabine (FDR) with synergistic drugs. We evaluated the efficacy
      and toxicity of a schedule that includes fludarabine, ara-C, novantrone and
      dexamethasone (FAND) for the management of previously treated CLL patients under
      60 years old. DESIGN AND METHODS: Thirty-one patients underwent FAND treatment.
      Twenty-three patients had active disease (relapsed patients: 9; unresponsive to
      prior therapy: 14). Eight patients had a partial response (PR) to prior therapy
      and were treated with the aim of further reducing residual disease. The FAND
      schedule included fludarabine (25 mg/m(2) i.v. days 1-3), ara-C (1 g/m(2) i.v.
      day 1: 8 patients; days 1-2: 23 patients), novantrone (10 mg/m(2) i.v. day 1) and
      dexamethasone (20 mg i.v. days 1-3). Infection prophylaxis consisted of
      fluconazole, acyclovir, trimethoprim/sulfamethoxasole and granulocyte colony
      stimulating factor (G-CSF) in the presence of severe neutropenia. RESULTS: A
      response was observed in 7/14 refractory patients (complete response-CR: 29%), in
      all 9 relapsed patients (CR: 78%) and in 7/8 patients (CR: 87.5%) treated in PR.
      Taken together, 18 CRs were obtained and in 14 (78%) this was associated with a
      flow cytometric remission (CD5+/CD20(weak+) PB lymphocytes: <10%). Severe
      granulocytopenia occurred after 86 of the 124 administered courses (69%), but
      only after 10/86 courses (12%) were major infections recorded. In 10/15 mobilized
      patients (cyclophosphamide + G-CSF: 6 patients; FAND + G-CSF: 9 patients) after
      FAND > or = 2 x 10(6)/kg CD34+ cells were collected. Nine patients were
      autografted in CR and showed a longer response duration than the 9 patients in CR
      who did not receive further therapy after FAND (53 vs 30% at 41 months; p =
      0.05). INTERPRETATION AND CONCLUSIONS: FAND associated with extensive infection
      prophylaxis and G-CSF support is a highly cytoreductive and well-tolerated
      treatment for CLL patients and in most cases does not hamper subsequent stem cell
      mobilization.

PMID- 12217805
TI  - Melphalan-prednisone versus alternating combination VAD/MP or VND/MP as primary
      therapy for multiple myeloma: final analysis of a randomized clinical study.
AB  - BACKGROUND AND OBJECTIVES: In the absence of a cure for multiple myeloma (MM)
      with standard-dose therapy, any strategy that can be expected to increase tumor
      reduction and to extend survival duration is likely to be of clinical relevance.
      The primary end-point of the present study was to investigate whether the
      alternating combination of vincristine-doxorubicin-dexamethasone (VAD) and
      melphalan-prednisone (MP) or vincristine-mitoxantrone-dexamethasone (VND) and MP
      could improve the clinical outcome of MM patients thus treated in comparison with
      those receiving MP alone. DESIGN AND METHODS: Between November 1990 and April
      1994, 527 previously untreated, stage I-III, MM patients from 29 Italian
      institutions were randomized to receive one of three remission induction
      chemotherapy regimens consisting of 8-monthly courses of either MP alone or
      alternating VAD/MP or VND/MP. RESULTS: On an intent-to-treat basis, the objective
      response rates were 53% with MP (objective + minor: 67%), 47% with VAD/MP
      (objective + minor: 61%) and 49% with VND/MP (objective + minor: 61%). Median
      survival duration was 36.5 months with MP, 29 months with VAD/MP and 32.5 months
      with VND/MP. The difference among these groups was not statistically significant,
      even after stratifying patients into high-risk and low-risk subgroups, as
      assessed by a multifactor proportional hazard analysis. In both younger and
      elderly patients, severe granulocytopenia and related infections were
      significantly more frequent with VND/MP compared to the remaining arms of
      treatment (p < 0.001 and p = 0.009, respectively). Similarly, the frequency of
      WHO grade III-IV cardiovascular events was significantly higher for patients
      receiving anthracycline-containing regimens (VND/MP and VAD/MP) than for those
      treated with MP alone (p = 0.04). INTERPRETATION AND CONCLUSIONS: Alternating
      VAD/MP and VND/MP failed to improve the clinical outcome for MM patients, at the
      cost of increased toxicity and morbidity. Resistance to standard-dose
      chemotherapy remains a significant obstacle to the treatment of MM.

PMID- 12217806
TI  - Defective expression of GPIb/IX/V complex in platelets from patients with May
      Hegglin anomaly and Sebastian syndrome.
AB  - BACKGROUND AND OBJECTIVES: May-Hegglin anomaly (MHA) and Sebastian syndrome (SBS)
      are inherited macrothrombocytopenias with D hle-like bodies in leukocytes. MHA
      SBS are due to mutations of the gene (MYH9) for the heavy chain of non-muscle
      myosin IIA (NMMHC-IIA), the only myosin II expressed in platelets. The bleeding
      tendency is often more severe than expected on the basis of platelet count, but
      no abnormality of platelet function has been identified. To characterize platelet
      abnormalities deriving from MYH9 mutations better, we studied surface
      glycoproteins (GPs) in platelets from MHA-SBS patients. DESIGN AND METHODS: Eight
      patients from 4 unrelated families were studied. Platelet surface GPs were
      studied by flow cytometry in both the whole platelet population and
      subpopulations of platelets identified according to their size. RESULTS: Flow
      cytometry identified a defect of the GPIb/IX/V complex in the whole platelet
      population in 7 of 8 patients. Moreover, in all patients the subpopulation of
      large platelets had defective expression of this complex. INTERPRETATION AND
      CONCLUSIONS: These findings indicate that MYH9 mutations may be responsible for
      reduced surface expression of GPIb/IX/V. This defect could contribute to the
      bleeding tendency of these patients. The identification of a GPIb/IX/V defect in
      MHA-SBS platelets raises the question of the differential diagnosis from
      heterozygous Bernard-Soulier syndrome.

PMID- 12217807
TI  - Intracranial bleeding: epidemiology and relationships with antithrombotic
      treatment in 241 cerebral hemorrhages in Reggio Emilia.
AB  - BACKGROUND AND OBJECTIVES: Anticoagulant (AC) and antiplatelet (AP) drugs are
      effectively used in the prevention of thromboembolic events, with the trade-off
      of bleeding side effects, particularly intracranial. The aim of this study was to
      determine the incidence of intracranial bleeding in the population of Reggio
      Emilia and to investigate the potential effect of AC and AP drugs. DESIGN AND
      METHODS: We reviewed all the patients admitted for cerebral hemorrhages to our
      hospital between April 1998 and September 2000. Data were collected with a
      standardized form. All the patients were followed-up to estimate long-term
      mortality. Chi(2) and t-tests were used as appropriate. Logistic regression
      analysis was performed to test predictors of mortality. Pharmaceutical department
      data were employed to estimate the total number of patients receiving AC and AP
      drugs. RESULTS: We found 241 cases (107/134 female/male, mean age 61 years,
      133/107 spontaneous/traumatic events, 0.32/1,000/year overall). Twenty-nine and
      47 of these patients were being given AC or AP drugs, respectively
      (4.9/1,000/year and 3.7/1,000/year). The relative risk of intracranial bleeding
      was 11.5 in AP and 15.3 in AC treated patients. Two patients (one underwent
      neurosurgery and one thrombolytic treatment) were excluded from mortality and
      risk factors analysis. Six patients were lost from follow-up and excluded from
      mortality analysis. Overall mortality was 100/233 (42.9%); mortality in traumatic
      events was 25/103 (24.2%) versus 75/130 (57.7%) in spontaneous events. Mortality
      was 19/29 (65.5%), 26/47 (55.3%) and 55/157 (35%) in AC recipients, AP
      recipients, and untreated patients, respectively. This increased risk was mainly
      confined to traumatic events (p = 0.06), without difference between AC and AP
      recipients. At the time of the event, the mean duration of oral AC treatment was
      26.3 months (range 1-120). Mean INR was = 3.1 (range 1.6-8.8). Mortality was
      significantly predicted by the Glasgow Coma Scale Score (GCS) at admission (p <
      0.0001), by the type of bleeding (spontaneous versus traumatic) (p = 0.0026), and
      by age (p < 0.0001). INTERPRETATION AND CONCLUSIONS: Careful selection of
      patients and prevention of traumatic events are the main candidate mechanisms to
      reduce intracranial bleeding in patients being treated with AC and AP drugs.

PMID- 12217808
TI  - Influence of age, sex and vitamin status on fasting and post-methionine load
      plasma homocysteine levels.
AB  - BACKGROUND AND OBJECTIVES: To investigate the effects of age, sex and vitamin
      status on total plasma homocysteine (tHCy), both after fasting (FtHCy) and two
      hours post-methionine load (PML-tHCy). The secondary aim was to determine the
      reference values for FtHCy and PML-tHCy. DESIGN AND METHODS: A cohort of
      apparently healthy volunteers underwent blood sampling for FtHCy, PML-tHCy,
      creatinine, serum folate, vitamin B12 and vitamin B6 (pyridoxal-5-phosphate,
      PLP). RESULTS: In 147 subjects (M/F= 82/65, age range: 14-94 years), FtHCy was
      significantly higher in men than in women. In men, age and folate levels
      explained 20.5% and 19.0% of FtHCy variance, respectively. In women, age and
      vitamin B12 accounted for 22.6% and 17.8% of FtHCy variance, respectively. PML
      tHCy was similar in men and women. PML-tHCy was negatively correlated with folate
      in both sexes, and with vitamin B12 and age in women only. Folate accounted for
      20% of the variance of PML-tHCy in men, while in women vitamin B12 and PLP
      explained 40% and 20% of variance of PML-tHCy, respectively. The reference values
      of FtHCy and PML-tHCy were: 19.63 and 40.18 mol/L, respectively, for men under 45
      years, 14.26 and 28.31 mol/L, respectively, for women under 45 years, 28.38 and
      36.48 mol/L for men above 45 years, and 22.49 and 44.06 mol/L for women above 45
      years. INTERPRETATION AND CONCLUSIONS: Age, gender and vitamin status influence
      both FtHCy and PML-tHCy in normal subjects. Reference values should be calculated
      according to age and sex.

PMID- 12217809
TI  - Allogeneic hematopoietic stem cell transplantation in patients 50 years of age
      and older.
AB  - BACKGROUND AND OBJECTIVES: The population of elderly patients with hematologic
      malignancies is increasing and so will the activity of stem cell transplantation
      (SCT) in this population. The aim of this study was to analyze the toxicity and
      survival of allogeneic SCT in patients 50 years and older (elderly group), and
      compare the results with a standard adult population (young group). DESIGN AND
      METHODS: Thirty-two elderly patients (median age 52.5, range 50-59 years) and 97
      young patients (median 32, range 20-40) received a myeloablative, allogeneic SCT
      from HLA-identical siblings at a single institution, and formed the basis of this
      retrospective study. The majority of transplants in both groups were performed
      with non-T-cell-depleted bone marrow, conditioned with busulfan +
      cyclophosphamide and received cyclosporine + methotrexate as graft-versus-host
      disease (GVHD) prophylaxis. The percentage of high-risk patients was nearly
      double in the elderly group (41% vs. 23%, p = 0.06). RESULTS: We observed a low
      incidence of toxicities in the elderly group, including veno-occlusive disease,
      acute and chronic GVHD, transplant-related mortality, time to engraftment, and
      relapse incidence, without significant differences compared within the young
      group. The 3-year survival rates were not statistically different between the
      elderly and young groups: 51% vs. 55% for all patients; 87% vs. 69% in chronic
      myeloid leukemia; 79% vs. 62% in standard risk patients and 13% vs. 31% in high
      risk ones. In multivariate analyses no significant difference in overall survival
      was found between age groups. INTERPRETATION AND CONCLUSIONS: According to our
      experience, age alone (between 50-59), should not be considered a
      contraindication to a conventional HLA identical sibling transplant.

PMID- 12217810
TI  - Treatment of acute graft versus host disease with low dose-alternate day anti
      thymocyte globulin.
AB  - BACKGROUND AND OBJECTIVES: The efficacy of antithymocyte globulin (ATG) in the
      treatment of graft-versus-host disease (GvHD) is controversial. In the present
      study we report on the use of low dose ATG (thymoglobuline, Sangstat) and
      steroids in 28 patients with moderate to severe acute GvHD. DESIGN AND METHODS:
      Fifteen patients received ATG as first-line treatment within 14 days of the
      diagnosis of GvHD (median 8 days, range 4-13). Twelve patients received ATG as
      second-line therapy, more than 14 days after diagnosis (median 32 days, range 14
      to 98). The proportion of patients with severe (grade III-IV) GvHD at the time of
      ATG therapy was 4/15 in the former group and 7/13 in the latter (p=0.1). RESULTS:
      On day 30 after ATG the overall proportion of responders was 80% in the group
      administered ATG early and 38% in those given it later (p=0.03). The overall
      actuarial 3-year transplant-related mortality was 40% vs 74% for the early vs
      late ATG groups (p=0.03); the actuarial 3-year survival was, respectively, 49% vs
      23% (p=0.04). For patients with GvHD grade III-IV the actuarial 1-year TRM was
      47% for those given ATG early, 87% for the late ATG group and 82% for a
      concurrent control group of 26 patients not treated with ATG. INTERPRETATION AND
      CONCLUSIONS: In conclusion, ATG may be considered for early treatment of acute
      GvHD, within a few days from the onset of the disease. A prospective trial has
      been started to test whether, in this setting, low dose ATG with steroids is
      superior to steroids alone.

PMID- 12217811
TI  - The use of imatinib (STI571) in chronic myelod leukemia: some practical
      considerations.
AB  - BACKGROUND AND OBJECTIVES: The new Abl tyrosine kinase inhibitor imatinib
      (imatinib mesylate, STI571) is very effective in the treatment of patients with
      chronic myeloid leukemia (CML). It induces complete hematologic control in >90%
      of patients with CML in chronic phase and preliminary data suggest that the
      incidence of complete cytogenetic remission may exceed 60% in previously
      untreated patients, though its capacity to prolong life in comparison with other
      agents has not yet been clearly established. It is also active in the management
      of patients in advanced phases of CML. INFORMATION SOURCES: We present here
      provisional indications for the use of imatinib in CML patients and give details
      of the dosage regimens we have used and side-effects we have encountered. STATE
      OF THE ART AND PERSPECTIVES: It is likely that the optimal usage of this
      important new agent will become better defined as more experience is gained.

PMID- 12217812
TI  - Idiotypic vaccination for B-cell malignancies as a model for therapeutic cancer
      vaccines: from prototype protein to second generation vaccines.
AB  - BACKGROUND AND OBJECTIVES: Cancer vaccines are aimed at inducing tumor-specific
      immunity by immunizing patients with tumor cells or their antigenic components,
      known as tumor-associated antigens (TAA). Antigens which are either mutated or
      selectively or abundantly expressed in malignant, but not in normal, cells are
      considered as TAA. Each patient's B-cell malignancy is usually derived from a
      single expanded B-cell clone, which expresses an immunoglobulin (Ig) with a
      unique idiotype (Id, variable regions of Ig). Therefore, Id can be regarded as a
      TAA and a potential target in clinical vaccination approaches. Although use of
      tumor-derived Id as an immunogen to elicit antitumor immunity against B-cell
      malignancies is an attractive idea, the broader use of idiotypic vaccines has
      been hampered by the fact that autologous Id is not only a weakly immunogenic,
      self antigen, but is also patient-specific so that the vaccine must be
      individually prepared for each patient. In this review we will first summarize
      the latest data from the clinical tests of experimental idiotypic vaccines and
      discuss issues relevant to the clinical application of cancer vaccines in
      general; we will then critically review new trends and achievements in the
      development of the second generation vaccine formulations. EVIDENCE AND
      INFORMATION SOURCES: The authors of the present review are currently working in
      the field of B-cell tumor immunotherapy and have contributed original papers to
      peer-reviewed journals. The material analyzed in the present review includes
      articles and abstracts published in journals covered by the Science Citation
      Index and Medline. STATE OF ART: The results from a number of experimental models
      and clinical trials have demonstrated that vaccination with tumor-derived Id can
      induce immune responses directed against the tumor. Idiotypic vaccines can be
      divided into two types, although both are at the experimental stage: traditional
      and second generation, based on the methods of production and vaccine delivery.
      Second generation vaccines utilizing genetically engineered protein and DNA
      formulations have, for the first time, opened up the possibility of streamlining
      production of simpler and effective custom-made idiotypic vaccines. The use of
      various adjuvants and exogenous carriers is being replaced by more potent genetic
      carriers which target Id and various co-stimulatory molecules to professional
      antigen presenting cells (APC), particularly dendritic cells (DC). PERSPECTIVES:
      Id is the only widely accepted tumor marker and is a promising therapeutic target
      for immunotherapy of B-cell malignancies. It has been unequivocally established
      that Id vaccination of patients with follicular lymphoma administered when
      patients have minimal residual disease, has antitumor effect and potential to
      improve the clinical outcome. Consequently, the applicability of Id vaccines for
      other B-cell malignancies such as chronic lymphocytic leukemia, mantle cell
      lymphoma and multiple myeloma needs to be tested. Idiotypic vaccines should be
      tailored to target preferentially various subsets of immune cells, such as DCs,
      which would up take and properly process and present Id, activating both arms of
      the immune system, humoral and cellular. Moreover, the vaccine should induce the
      production of a milieu of inflammatory cytokines and lymphokines at the delivery
      site to elicit a T helper type 1 (Th1) immune response. Components of the
      inflammatory response can be used to target DCs in vivo, activating the so-called
      danger signal for circumventing the poor immunogenicity of self-tumor antigens.
      For example, chemotactic factors of innate immunity are able to deliver Id to APC
      and render this otherwise non-immunogenic antigen immunogenic. The strategies
      developed for Id vaccines can be used as a general strategy for eliciting T-cell
      immunity to other weakly immunogenic, clinically relevant self-tumor antigens.

PMID- 12217813
TI  - Beta- and alpha-globin genotypes in Albanian patients affected by beta-globin
      gene disorders.
AB  - We investigated the molecular basis of hemoglobinopathies and restriction
      fragment length polymorphism (RFLP) haplotypes in 58 unrelated Albanian patients.
      A wise heterogeneity was detected, characterized by 11 beta-thalassemia, 3 Hb
      variant and 4 alpha-globin alleles. All beta-thalassemia and Hb variant alleles
      were associated with the same haplotypes described in other populations. Genotype
      phenotype correlation was established.

PMID- 12217814
TI  - Late response to donor lymphocyte infusions in patients with chronic myeloid
      leukemia relapsing after allogeneic stem cell transplantation.
AB  - Donor lymphocyte infusions were given to 13 consecutive chronic myeloid leukemia
      patients in relapse after allogeneic stem cell transplantation. Of the 13
      patients, 11 achieved a molecular remission and 2 a cytogenetic remission. The
      median time (range) in months to achieve a hematologic, cytogenetic and molecular
      remission was 2 (1-2), 5 (1-42) and 5 the median response duration is 16 months
      (range 1-36), and no patient shows evidence of relapse.

PMID- 12217815
TI  - Nuclear factor k B is activated in myelodysplastic bone marrow cells.
AB  - We describe a significant increase in the DNA binding activity of nuclear factor
      kappa B (NF kappa B) in bone marrow cells from patients with myelodysplastic
      syndrome (MDS) compared with normal donor cells. Furthermore, MDS samples with
      increased NFkappaB activity consistently showed higher mRNA levels of NFkappaB
      regulated cytokines.

PMID- 12217816
TI  - Erythropoietin does not modify the prothrombotic effect induced by uremic media
      on endothelial cells.
AB  - Recombinant human erythropoietin (rHuEPO) administration has been associated with
      an increased risk of hypertension and thrombosis in uremic patients. rHuEPO and
      endothelial cells cultured in an uremic environment. Results indicate that rHuEPO
      does not exert an additional activating effect to that caused by the uremic media
      per se.

PMID- 12217819
TI  - Diabetes: preventing complications that kill. Part II: A comprehensive program.

PMID- 12217820
TI  - The digital rectal exam: still useful after all these years?

PMID- 12217821
TI  - Rosacea: red in the face.

PMID- 12217822
TI  - On call. I've noticed that my newspaper always seems to have a story about
      testicular cancer in an athlete. Do athletes really get the disease more often
      than ordinary men?

PMID- 12217823
TI  - On call. I don't trust the claims of all the new herbal drugs and products. Many
      claim to be clinically proven. What does that mean? Is this valid scientific
      research? If not, why are such claims tolerated by the medical world?

PMID- 12217824
TI  - Dialectical behavior therapy.

PMID- 12217825
TI  - Early detection of Alzheimer's disease.

PMID- 12217826
TI  - Smoking and depression.

PMID- 12217827
TI  - Screening for depression.

PMID- 12217828
TI  - Nefazodone and liver damage.

PMID- 12217829
TI  - How you can lower your cancer risk.

PMID- 12217830
TI  - Six tips for preventing falls and fractures.

PMID- 12217831
TI  - Gases of the gut.

PMID- 12217832
TI  - Your best bets for preventing Alzheimer's disease.

PMID- 12217839
TI  - By the way, doctor. My husband is 72 and had a bad heart attack six months ago.
      He is so depressed and some days barely wants to get out of bed. He says, "Of
      course I'm depressed. I have a bad heart." My son thinks he ought to be taking an
      antidepressant.

PMID- 12217840
TI  - By the way doctor. Last fall, my mother went into a deep depression. The same
      thing happened about five years ago, but she took an antidepressant for a few
      weeks and it went away. This time she's been depressed for nearly a year. No
      medication has helped. Now her doctors want her to try electroshock therapy, but
      that scares her--and me.

PMID- 12217841
TI  - By the way, doctor. I remember reading that bacteria might be the cause of heart
      disease, but I haven't seen anything about it lately. Did that research reach a
      dead end?

PMID- 12217843
TI  - Battling the bulge: when to operate for ballooning blood vessels.

PMID- 12217842
TI  - File a personal flight plan to prevent blood clots.

PMID- 12217844
TI  - Tea and heart disease.

PMID- 12217845
TI  - Deliver me from temptation. The danger of...just one fatty meal...just one
      cigarette.

PMID- 12217846
TI  - A hospital transfer for improved heart attack therapy.

PMID- 12217847
TI  - Nerve damage rare but possible with cholesterol-lowering drugs.

PMID- 12217848
TI  - Ask the doctor. I have atherosclerosis in the arteries of my heart and neck, and
      my doctors want me to take aspirin. I also have arthritis and take Naprosyn for
      it every day. I have heard that Naprosyn can prevent blood clots, just like
      aspirin does. Can I just take Naprosyn, or do I still need to take aspirin, too,
      to protect my heart and brain from blood clots?

PMID- 12217849
TI  - Diabetic kidney disease: impact of puberty.
AB  - Puberty accelerates microvascular complications of diabetes mellitus, including
      nephropathy. Animal studies confirm a different renal hypertrophic response to
      diabetes before and after puberty, probably due to differences in the production
      of transforming growth factor-beta (TGF-beta). Many of the complex physiological
      changes during puberty could affect potentially pathogenic mechanisms of diabetic
      kidney disease. Increased blood pressure, activation of the growth hormone
      insulin-like growth factor I axis, and production of sex steroids could all play
      a role in pubertal susceptibility to diabetic renal hypertrophy and nephropathy.
      These factors may influence the effects of hyperglycemia and several systems that
      ultimately control TGF-beta production, including the renin-angiotensin system,
      cellular redox systems, the polyol pathway, and protein kinase C. These phenomena
      may also explain gender differences in kidney function and incidence of end-stage
      renal disease. Normal changes during puberty, when coupled with diabetes and
      superimposed on a genetically susceptible milieu, are capable of accelerating
      diabetic hypertrophy and microvascular lesions. A better understanding of these
      processes may lead to new treatments to prevent renal failure in diabetes
      mellitus.

PMID- 12217850
TI  - Xenotransplantation of developing kidneys.
AB  - The number of kidney transplants performed per year is limited by the
      availability of donor organs. One novel solution to this shortage envisions
      "growing" new kidneys in situ via xenotransplantation of renal anlagen. We have
      shown that developing metanephroi transplanted into the omentum of animal hosts
      undergo differentiation and growth, become vascularized by blood vessels of host
      origin, and exhibit excretory function. Metanephroi can be stored for up to 3
      days in vitro before transplantation with no impairment in growth or function
      postimplantation. Metanephroi can be transplanted across both concordant (rat -->
      mouse) and discordant/highly disparate (pig --> rodent) xenogeneic barriers. This
      review summarizes experimental data relating to the transplantation of developing
      kidneys.

PMID- 12217851
TI  - A functional interaction between CHIF and Na-K-ATPase: implication for regulation
      by FXYD proteins.
AB  - Like the gamma-subunit of Na-K-ATPase, the corticosteroid hormone-induced factor
      (CHIF) is a member of the FXYD family of one-transmembrane-segment proteins. Both
      CHIF and two splice variants of gamma, gamma(a) and gamma(b), are expressed in
      the kidney. Immunolocalization experiments demonstrate mutually exclusive
      expression of CHIF and gamma in different nephron segments. Specific
      coimmunoprecipitation experiments demonstrate the existence in kidney membranes
      of the complexes alpha/beta/gamma(a), alpha/beta/gamma(b), and alpha/beta/CHIF
      and exclude mixed complexes such as alpha/beta/gamma(a)/gamma(b) and
      alpha/beta/gamma/CHIF. CHIF has been expressed in HeLa cells harboring the rat
      alpha(1)-subunit of Na-K-ATPase. (86)Rb flux experiments demonstrate that CHIF
      induces a two- to threefold increase in apparent affinity for cytoplasmic Na
      (K'(Na)) but does not affect affinity for extracellular K (Rb) ions (K'(K)) or
      V(max). Measurements of Na-K-ATPase using isolated membranes show similar but
      smaller effects of CHIF on K'(Na), whereas K'(K) and K'(ATP) are unaffected. The
      functional effects of CHIF differ from those of gamma. An implication of these
      findings is that other FXYD proteins could act as tissue-specific modulators of
      Na-K-ATPase.

PMID- 12217852
TI  - Mast cells mediate substance P-induced bladder inflammation through an NK(1)
      receptor-independent mechanism.
AB  - The role of neurokinin-1 receptors (NK1R) in the interaction between mast cells
      and substance P (SP) in bladder inflammation was determined. Mast cell-deficient
      Kit(W)/Kit(W-v), congenic normal (+/+), and Kit(W)/Kit(W-v) mice that were
      reconstituted with bone marrow cells isolated from NK1R(-/-) mice were challenged
      by instillation of SP, antigen, or saline into the urinary bladder. Twenty-four
      hours after challenge, the bladders were prepared for morphological assessment
      and gene expression. SP-induced bladder inflammation was mast cell dependent and
      did not require NK1R expression on the mast cell. Cluster analysis identified
      functionally significant genes that were dependent on the presence of mast cells
      for their upregulation regardless of stimulus. Those include serine protein
      inhibitor 2.2, maspin, mitogen- and stress-activated protein kinase 2, and
      macrophage colony-stimulating factor 1. Our findings demonstrate that while mast
      cells are essential for both antigen- and SP-induced bladder inflammation, there
      are common genes and unique genes expressed in each type of inflammatory
      reaction. When combined with unique animal models, gene array analysis provides a
      useful approach for identifying and characterizing pathways involved in bladder
      inflammation.

PMID- 12217853
TI  - Evidence for endocytosis of ROMK potassium channel via clathrin-coated vesicles.
AB  - ROMK channels are present in the cortical collecting ducts of kidney and are
      responsible for K(+) secretion in this nephron segment. Recent studies suggest
      that endocytosis of ROMK channels is important for regulation of K(+) secretion
      in cortical collecting ducts. We investigated the molecular mechanisms for
      endocytosis of ROMK channels expressed in Xenopus laevis oocytes and cultured
      Madin-Darby canine kidney cells. When plasma membrane insertion of newly
      synthesized channel proteins was blocked by incubation with brefeldin A, ROMK
      currents decreased with a half-time of ~6 h. Coexpression with the Lys44-->Ala
      dominant-negative mutant dynamin, but not wild-type dynamin, reduced the rate of
      reduction of ROMK in the presence of brefeldin A. Mutation of Asn371 to Ile in
      the putative NPXY internalization motif of ROMK1 abolished the effect of the
      Lys44-->Ala dynamin mutant on endocytosis of the channel. Coimmunoprecipitation
      study and confocal fluorescent imaging revealed that ROMK channels associated
      with clathrin coat proteins in Madin-Darby canine kidney cells. These results
      provide compelling evidence for endocytosis of ROMK channels via clathrin-coated
      vesicles.

PMID- 12217854
TI  - Fatty acids exacerbate tubulointerstitial injury in protein-overload proteinuria.
AB  - The role of the albumin-carried fatty acids in the induction of
      tubulointerstitial injury was studied in protein-overload proteinuria. Rats were
      injected with fatty acid-carrying BSA [FA(+)BSA], fatty acid-depleted BSA [FA(
      )BSA], or saline. Macrophage infiltration was measured by immunohistochemical
      staining, apoptotic cells were detected by in situ end labeling, and
      proliferating cells were identified by in situ hybridization for histone mRNA.
      Macrophage infiltration was significantly greater in the FA(+)BSA group than in
      the FA(-)BSA and saline groups. The infiltrate was largely restricted to the
      outer cortex. Apoptosis was greater in the FA(+)BSA group than in the FA(-)BSA
      and saline groups. Compared with the saline group, apoptosis was significantly
      increased in the FA(+)BSA group but not in the FA(-)BSA group. Cortical cells
      proliferated significantly more in the FA(+)BSA and FA(-)BSA groups than in the
      saline group. FA(+)BSA is therefore a more potent inducer of macrophage
      infiltration and cell death than FA(-)BSA. The fatty acids carried on albumin may
      be the chief instigators of tubulointerstitial injury in protein-overload
      proteinuria.

PMID- 12217855
TI  - Time course of renal Na-K-ATPase, NHE3, NKCC2, NCC, and ENaC abundance changes
      with dietary NaCl restriction.
AB  - We have used peptide-directed antibodies to each major renal Na transporter and
      channel proteins to screen renal homogenates for changes in Na transporter
      protein expression after initiation of dietary NaCl restriction. After
      equilibration on a NaCl-replete diet (2.0 meq. 200 g body wt(-1). day(-1)), rats
      were switched to a NaCl-deficient diet (0.02 meq. 200 g body wt(-1). day(-1)). Na
      excretion fell to 25% of baseline levels on day 1, followed by a further decrease
      <4% of baseline levels on day 3, of NaCl restriction. The decreased Na excretion
      at day 1 occurred despite the absence of a significant increase in plasma
      aldosterone level or in the abundance of any of the major renal Na transporters.
      However, after a 1-day lag, plasma aldosterone levels increased in association
      with increases in abundances of three aldosterone-regulated Na transporter
      proteins: the thiazide-sensitive Na-Cl cotransporter (NCC), the alpha-subunit of
      the amiloride-sensitive epithelial Na channel (alpha-ENaC), and the 70-kDa form
      of gamma-ENaC. RNase protection assays of transporter mRNA levels revealed an
      increase in renal alpha-ENaC mRNA coincident with the increase in alpha-ENaC
      protein abundance. However, there was no change in NCC mRNA abundance, suggesting
      that the increase in NCC protein in response to dietary NaCl restriction was not
      a result of altered gene transcription. These results point to early regulatory
      processes that decrease renal Na excretion without an increase in the abundance
      of any Na transporter, followed by a late aldosterone-dependent response
      associated with upregulation of NCC and ENaC.

PMID- 12217856
TI  - Role of iNOS and eNOS in modulating proximal tubule transport and acid-base
      balance.
AB  - Our laboratory has previously shown that mice lacking neuronal nitric oxide
      synthase (nNOS) are defective in fluid absorption (J(v)) and HCO absorption
      (J(HCO3)) in the proximal tubule and develop metabolic acidosis. The present
      study examined the transport of fluid and HCO in the proximal tubule and acid
      base status in mice lacking two other isoforms of NOS, inducible NOS (iNOS) and
      endothelial NOS (eNOS). Proximal tubules were microperfused in situ in wild-type
      and NOS knockout mice by methods previously described (Wang T, Yang C-L, Abbiati
      T, Schultheis PJ, Shull GE, Giebisch G, and Aronson PS. Am J Physiol Renal
      Physiol 277: F298-F302, 1999). [(3)H]inulin and total CO(2) concentrations were
      measured in the perfusate and collected fluid, and net J(v) and J(HCO3) were
      analyzed. These data show that J(HCO3) was 35% lower (71.7 +/- 6.4 vs. 109.9 +/-
      7.3 pmol x min(-1) x mm(-1), n = 13, P < 0.01) and J(v) was 38% lower (0.95 +/-
      0.15 vs. 1.54 +/- 0.17 nl. min(-1) x mm(-1), n = 13, P < 0.05) in iNOS knockout
      mice compared with their wild-type controls. Addition of the iNOS-selective
      inhibitor L-N(6)-(1-iminoethyl) lysine, reduced both J(v) and J(HCO3)
      significantly in wild-type, but not in iNOS knockout, mice. In contrast, both
      J(HCO3) (93.3 +/- 7.9 vs. 110.6 +/- 6.18 pmol x min(-1) x mm(-1)) and J(v) (1.56
      +/- 0.17 vs. 1.55 +/- 0.16 nl. min(-1) x mm(-1)) did not change significantly in
      eNOS knockout mice. These results indicated that iNOS upregulates Na(+) and HCO
      transport, whereas eNOS does not directly modulate Na(+) and HCO transport in the
      kidney proximal tubules.

PMID- 12217857
TI  - A central role for Pyk2-Src interaction in coupling diverse stimuli to increased
      epithelial NBC activity.
AB  - Regulation of renal Na-HCO cotransporter (NBC1) activity by cholinergic agonists,
      ANG II, and acute acidosis (CO(2)) requires both Src family kinase (SFK) and
      classic MAPK pathway activation. The nonreceptor tyrosine kinase proline-rich
      tyrosine kinase 2 (Pyk2) couples discrete G protein-coupled receptor and growth
      factor receptor signaling to SFK activation. We examined the role of Pyk2-SFK
      interaction in coupling these stimuli to increased NBC1 activity in opossum
      kidney cells. Carbachol increased tyrosine autophosphorylation of endogenous Pyk2
      and ectopically expressed wild-type Pyk2 and were abrogated by kinase-dead mutant
      (Pyk2-KD) overexpression. Pyk2 phosphorylation was calcium/calmodulin dependent,
      and Pyk2 associated with Src by means of SH2 domain interaction. Pyk2
      phosphorylation and Pyk2-Src interaction by carbachol were mimicked by both ANG
      II and CO(2). To correlate Pyk2 autophosphorylation and Pyk2-Src interaction with
      NBC activity, cotransporter activity was measured in untransfected cells and in
      cells overexpressing Pyk2-KD in the presence or absence of carbachol, ANG II, or
      CO(2). In Pyk2-KD-overexpressing cells, the effect of carbachol, ANG II, and
      CO(2) was abolished. We conclude that Pyk2 plays a central role in coupling
      carbachol, ANG II, and CO(2) to increased NBC activity. This coupling is mediated
      by Pyk2 autophosphorylation and Pyk2-Src interaction.

PMID- 12217858
TI  - K depletion increases protein tyrosine kinase-mediated phosphorylation of ROMK.
AB  - We purified His-tagged ROMK1 and carried out in vitro phosphorylation assays with
      (32)P-radiolabeled ATP to determine whether ROMK1 protein is a substrate for PTK.
      Addition of active c-Src and [(32)P]ATP to the purified ROMK1 protein resulted in
      the phosphorylation of the ROMK1 protein. However, c-Src did not phosphorylate
      R1Y337A in which tyrosine residue 337 was mutated to alanine. Furthermore,
      phosphopeptide mapping identified two phosphopeptides from the trypsin-digested
      ROMK1 protein. In contrast, no phosphorylated peptide has been found in the
      trypsin-digested R1Y337A protein. This suggested that two phosphorylated peptides
      might contain the same tyrosine residue. Also, addition of c-Src and [(32)P]ATP
      phosphorylated the synthesized peptide corresponding to amino acid sequence 333
      362 of the COOH terminus of ROMK1. We then examined the effect of dietary K
      intake on the tyrosine-phosphorylated ROMK level. Although the ROMK channels
      pulled down by immunoprecipitation with ROMK antibody were the same from rats on
      a K-deficient diet or on a high-K diet, more ROMK channels were phosphorylated by
      PTK in rats on a K-deficient diet than those on a high-K diet. We conclude that
      ROMK1 can be phosphorylated by PTK and that tyrosine residue 337 is the key site
      for the phosphorylation. Also, the tyrosine phosphorylation of ROMK is modulated
      by dietary K intake. This strongly suggests that PTK is an important member of
      the aldosterone-independent signal transduction pathway for regulating renal K
      secretion.

PMID- 12217859
TI  - p38 MAPK mediates acid-induced transcription of PEPCK in LLC-PK(1)-FBPase(+)
      cells.
AB  - LLC-PK(1)-FBPase(+) cells are a gluconeogenic and pH-responsive renal proximal
      tubule-like cell line. On incubation with acidic medium (pH 6.9), LLC-PK(1)
      FBPase(+) cells exhibit an increased rate of ammonia production as well as
      increases in glutaminase and phosphoenolpyruvate carboxykinase (PEPCK) mRNA
      levels and enzyme activities. The increase in PEPCK mRNA is due to an enhanced
      rate of transcription that is initiated in response to intracellular acidosis.
      The involvement of known MAPK activities (ERK1/2, SAPK/JNK, p38) in the
      associated signal transduction pathway was examined by determining the effects of
      specific MAPK activators and inhibitors on basal and acid-induced PEPCK mRNA
      levels. Transfer of LLC-PK(1)-FBPase(+) cultures to acidic medium resulted in
      specific phosphorylation, and thus activation, of p38 and of activating
      transcription factor-2 (ATF-2), respectively. Anisomycin (AI), a strong p38
      activator, increased PEPCK mRNA to levels comparable to those observed with acid
      stimulation. AI also induced a time-dependent phosphorylation of p38 and ATF-2.
      SB-203580, a specific p38 inhibitor, blocked both acid- and AI-induced PEPCK mRNA
      levels. Western blot analyses revealed that the SB-203580-sensitive p38alpha
      isoform is strongly expressed. The octanucleotide sequence of the cAMP-response
      element-1 site of the PEPCK promotor is a perfect match to the consensus element
      for binding ATF-2. The specificity of ATF-2 binding was proven by ELISA. We
      conclude that the SB-203580-sensitive p38alpha-ATF-2 signaling pathway is a
      likely mediator of the pH-responsive induction of PEPCK mRNA levels in renal LLC
      PK(1)-FBPase(+) cells.

PMID- 12217860
TI  - Localization of IP in rabbit kidney and functional role of the PGI(2)/IP system
      in cortical collecting duct.
AB  - To clarify the role of the PGI(2)/PGI(2) receptor (IP) system in rabbit cortical
      collecting duct (RCCD), we characterized the expression of IP receptors in the
      rabbit kidney. We show by Northern and Western blotting that IP mRNA and protein
      was detectable in all three regions of the kidney. To determine how PGI(2)
      signals, we compared the effects of different PGI(2) analogs [iloprost (ILP),
      carba-prostacyclin (c-PGI(2)), and cicaprost (CCP)] in the isolated perfused
      RCCD. PGI(2) analogs did not increase water flow (L(p)). Although PGI(2) analogs
      did not reduce an established L(p) response to 8-chlorophenylthio-cAMP, they
      equipotently inhibited AVP-stimulated L(p) by 45%. The inhibitory effect of ILP
      and c-PGI(2) on AVP-stimulated L(p) is partially reversed by the protein kinase C
      inhibitor staurosporine and abolished by pertussis toxin; no effect was obtained
      with CCP. In fura 2-loaded RCCD, CCP did not alter cytosolic Ca(2+) concentration
      ([Ca(2+)](i)), but, in the presence of CCP, individual infusion of ILP and PGE(2)
      increased [Ca(2+)](i), suggesting that CCP did not cause desensitization to
      either ILP or PGE(2). We concluded that ILP and c-PGI(2) activate PKC and the
      liberation of [Ca(2+)](i) but not CCP. This suggested an important role for
      phosphatidylinositol hydrolysis in mediating ILP and c-PGI(2) effects but not CCP
      in RCCD.

PMID- 12217861
TI  - Aldosterone inhibits HCO absorption via a nongenomic pathway in medullary thick
      ascending limb.
AB  - Rapid actions of aldosterone that are independent of transcription and
      translation have been described in a variety of cells; however, whether
      nongenomic pathways mediate aldosterone-induced regulation of renal tubule
      transport has not been determined. We report here that aldosterone induces rapid
      (<3.5 min) inhibition of HCO absorption in the medullary thick ascending limb
      (MTAL) of the rat. This inhibition is observed over the physiological range of
      hormone concentrations (IC(50) approximately 0.6 nM) and is not affected by
      pretreatment with actinomycin D (12.5 microg/ml), cycloheximide (40 microg/ml),
      or spironolactone (10 microM). The glucocorticoids dexamethasone, cortisol, and
      corticosterone (1 or 500 nM) did not affect HCO absorption in the absence or
      presence of carbenoxolone. Thus the specificity of rapid aldosterone action is
      not dependent on 11beta-hydroxysteroid dehydrogenase activity. The inhibition by
      aldosterone is additive to inhibition by angiotensin II and vasopressin,
      indicating that these factors regulate MTAL transport through distinct pathways.
      These results demonstrate that aldosterone inhibits HCO absorption in the MTAL
      via a pathway that is rapid, highly selective, independent of transcription and
      protein synthesis, and not mediated through the classic mineralocorticoid
      receptor. The results establish a role for nongenomic pathways in mediating
      aldosterone-induced regulation of transepithelial transport in the mammalian
      kidney. The novel action of aldosterone to inhibit luminal acidification in the
      MTAL may play a role in enabling the kidney to regulate acid-base balance
      independently of Na(+) balance and extracellular fluid volume.

PMID- 12217863
TI  - Epithelial Na channels and short-term renal response to salt deprivation.
AB  - To test the role of epithelial Na channels in the day-to-day regulation of renal
      Na excretion, rats were infused via osmotic minipumps with the Na channel blocker
      amiloride at rates that achieved drug concentrations of 2-5 microM in the lumen
      of the distal nephron. Daily Na excretion rates were unchanged, although
      amiloride-treated animals tended to excrete more Na in the afternoon and less in
      the late evening than controls. When the rats were given a low-Na diet, Na
      excretion rates were elevated in the amiloride-treated group within 4 h and
      remained higher than controls for at least 48 h. Adrenalectomized animals
      responded similarly to the low-Na diet. In contrast, rats infused with
      polythiazide at rates designed to inhibit NaCl transport in the distal tubule
      were able to conserve Na as well as did the controls. Injection of aldosterone (2
      microg/100 g body wt) decreased Na excretion in control animals after a 1-h
      delay. This effect was largely abolished in amiloride-treated rats. On the basis
      of quantitative analysis of the results, we conclude that activation of amiloride
      sensitive channels by mineralocorticoids accounts for 50-80% of the immediate
      natriuretic response of the kidney to a reduction in Na intake. Furthermore, the
      channels are necessary to achieve minimal rates of Na excretion during more
      chronic Na deprivation.

PMID- 12217862
TI  - TGF-beta and CTGF have overlapping and distinct fibrogenic effects on human renal
      cells.
AB  - Transforming growth factor-beta (TGF-beta) and connective tissue growth factor
      (CTGF) are ubiquitously expressed in various forms of tissue fibrosis, including
      fibrotic diseases of the kidney. To clarify the common and divergent roles of
      these growth factors in the cells responsible for pathological extracellular
      matrix (ECM) deposition in renal fibrosis, the effects of TGF-beta and CTGF on
      ECM expression in primary human mesangial (HMCs) and human proximal tubule
      epithelial cells (HTECs) were studied. Both TGF-beta and CTGF significantly
      induced collagen protein expression with similar potency in HMCs. Additionally,
      alpha(2)(I)-collagen promoter activity and mRNA levels were similarly induced by
      TGF-beta and CTGF in HMCs. However, only TGF-beta stimulated collagenous protein
      synthesis in HTECs. HTEC expression of tenascin-C (TN-C) was increased by TGF
      beta and CTGF, although TGF-beta was the more potent inducer. Thus both growth
      factors elicit similar profibrogenic effects on ECM production in HMCs, while
      promoting divergent effects in HTECs. CTGF induction of TN-C, a marker of
      epithelial-mesenchymal transdifferentiation (EMT), with no significant induction
      of collagenous protein synthesis in HTECs, may suggest a more predominant role
      for CTGF in EMT rather than induction of excessive collagen deposition by HTECs
      during renal fibrosis.

PMID- 12217864
TI  - Spatial repression of PCNA by p53 during kidney development.
AB  - Transcriptional repression is a key mechanism for the spatial specification of
      gene expression and cell fate determination. During kidney development,
      proliferating cell nuclear antigen (PCNA) is expressed in the nephrogenic zone
      and is downregulated rapidly as renal epithelial cells enter terminal
      differentiation and acquire functional characteristics. Our laboratory reported
      that the transcription factor p53 stimulates the terminal differentiation of
      renal epithelial cells by means of transcriptional activation of renal function
      genes (Saifudeen Z, Dipp S, and El-Dahr SS. J Clin Invest 109: 1021-1030, 2002).
      Because p53-induced growth arrest correlates with downregulation of PCNA gene
      expression, we examined the impact of p53 inactivation on PCNA expression in mice
      and evaluated the effect of p53 on PCNA transcription. Immunohistochemistry
      revealed that the transition from nephrogenesis to terminal epithelial cell
      differentiation correlates with accumulation of the transcription factor p53.
      Importantly, the spatially restricted pattern of PCNA expression is disrupted in
      kidneys of p53-deficient pups, in which there was a redistribution of PCNA
      expression into the differentiation zone (without a change in total kidney PCNA
      content) and distortion of the tubular architecture. Electrophoretic mobility
      shift assays revealed that the binding of kidney nuclear extracts to the p53
      response elements in human and rat PCNA promoters is developmentally regulated.
      Transient transfection assays performed in p53-deficient HeLa cells revealed that
      exogenous p53 strongly represses transcription from human PCNA promoter-reporter
      constructs. Interestingly, deletion of the p53-binding site confers enhanced
      responsiveness to p53-mediated repression, suggesting that transcriptional
      repression of PCNA by p53 is achieved by a mechanism other than direct DNA
      binding. On the basis of these results, we propose the hypothesis that p53
      mediated transcriptional repression plays a role in the spatial restriction of
      PCNA gene expression during normal renal development.

PMID- 12217865
TI  - CD2-associated protein directly interacts with the actin cytoskeleton.
AB  - CD2-associated protein (CD2AP) is an adapter protein associating with several
      membrane proteins, including nephrin, mutated in congenital nephrotic syndrome of
      the Finnish type, and polycystin-2, mutated in type 2 autosomal dominant
      polycystic kidney disease. Both proteins have critical roles in the maintenance
      of the integrity of the nephrons. Previous studies have suggested a role for
      CD2AP in the regulation of the organization of the actin cytoskeleton, but it has
      not been known whether the postulated association between CD2AP and actin is
      direct or mediated by other proteins. In this study, we address this question by
      using various cellular and biochemical approaches. We show that CD2AP and F-actin
      partially colocalize in cultured cells and that disruption of the actin
      cytoskeleton results in disorganization of endogenous CD2AP. Using cytoskeletal
      fractionation by differential centrifugation, we demonstrate that a proportion of
      CD2AP associates with the actin cytoskeleton. Furthermore, using pure actin and
      purified CD2AP fusion proteins in an F-actin coprecipitation assay, we show that
      CD2AP directly associates with filamentous actin and that this interaction is
      mediated by means of the COOH terminus of CD2AP. The present results suggest that
      CD2AP is involved in the regulation of the actin cytoskeleton and indicate that
      CD2AP may act as a direct adapter between the actin cytoskeleton and cell
      membrane proteins, such as nephrin and polycystin-2. Alterations in these
      interactions could explain some of the pathophysiological changes in congenital
      nephrotic syndrome and polycystic kidney disease.

PMID- 12217866
TI  - Immunocytochemical localization of pendrin in intercalated cell subtypes in rat
      and mouse kidney.
AB  - Recent studies have demonstrated that a novel anion exchanger, pendrin, is
      expressed in the apical domain of type B intercalated cells in the mammalian
      collecting duct. The purpose of this study was 1) to determine the expression and
      distribution of pendrin along the collecting duct and connecting tubule of mouse
      and rat kidney and establish whether pendrin is expressed in the non-A-non-B
      intercalated cells and 2) to determine the intracellular localization of pendrin
      in the different populations of intercalated cells by immunoelectron microscopy.
      A peptide-derived affinity-purified antibody was generated that specifically
      recognized pendrin in immunoblots of rat and mouse kidney. Immunohistochemistry
      and confocal laser scanning microscopy demonstrated the presence of pendrin in
      apical domains of all type B intercalated cells in mouse and rat connecting
      tubule and collecting duct. In addition, strong pendrin immunostaining was
      observed in non-A-non-B intercalated cells. There was no labeling of type A
      intercalated cells. Immunoelectron microscopy demonstrated that pendrin was
      located in the apical plasma membrane and intracellular vesicles of both type B
      intercalated cells and non-A-non-B cells; the latter was identified by the
      presence of H(+)-ATPase in the apical plasma membrane. The results of this study
      demonstrate that both pendrin and H(+)-ATPase are expressed in the apical plasma
      membrane of non-A-non-B intercalated cells, suggesting that these cells are
      capable of both HCO and proton secretion. Furthermore, the presence of pendrin in
      both the apical plasma membrane and the apical intracellular vesicles of type B
      and non-A-non-B intercalated cells suggests that HCO secretion may be regulated
      by trafficking of pendrin between the two membrane compartments.

PMID- 12217867
TI  - ANG II AT(1) and AT(2) receptors in developing kidney of normal microswine.
AB  - To identify an appropriate model of human renin-angiotensin system (RAS)
      involvement in fetal origins of adult disease, we quantitated renal ANG II AT(1)
      and AT(2) receptors (AT1R and AT2R, respectively) in fetal (90-day gestation, n =
      14), neonatal (3-wk, n = 5), and adult (6-mo, n = 8) microswine by
      autoradiography ((125)I-labeled [Sar(1)Ile(8)]ANG II+cold CGP-42112 for AT1R,
      (125)I-CGP-42112 for AT2R) and by whole kidney radioligand binding. The
      developmental pattern of renal AT1R in microswine, like many species, exhibited a
      10-fold increase postnatally (P < 0.001), with maximal postnatal density in
      glomeruli and lower density AT1R in extraglomerular cortical and outer medullary
      sites. With aging, postnatal AT1R glomerular profiles increased in size (P <
      0.001) and fractional area occupied (P < 0.04), with no change in the number per
      unit area. Cortical levels of AT2R by autoradiography fell with age from
      congruent with 5,000 fmol/g in fetal kidneys to congruent with 60 and 20% of
      fetal levels in neonatal and adult cortex, respectively (P < 0.0001). The pattern
      of AT2R binding in postnatal pig kidney mimicked that described in human and
      simian, but not rodent, species: dense AT2R confined to discrete cortical
      structures, including pre- and juxtaglomerular, but not intraglomerular,
      vasculature. Our results provide a quantitative assessment of ANG II receptors in
      developing pig kidney and document the concordance of pigs and primates in
      developmental regulation of renal AT1R and AT2R.

PMID- 12217868
TI  - On the natriuretic effect of verapamil: inhibition of ENaC and transepithelial
      sodium transport.
AB  - The natriuretic effect of Ca(2+) channel blockers has been attributed to
      hemodynamic changes and to poorly defined direct tubular effects. To test the
      possibility that verapamil may inhibit Na(+) reabsorption at the distal tubule,
      its effect on transepithelial Na(+) transport in aldosterone-stimulated A6 cells
      was determined. Cells were grown on permeable supports, and short-circuit current
      (I(sc)) measured in an Ussing chamber was used as a surrogate marker for
      transepithelial Na(+) transport. Application of 300 microM verapamil to the
      apical side inhibited I(sc) by 77% and was nearly as potent as 100 microM
      amiloride, which inhibited I(sc) by 87%. Verapamil-induced inhibition of I(sc)
      was accompanied by a significant increase in transepithelial resistance,
      suggesting blockade of an apical conductance. Its action on transepithelial Na(+)
      transport does not appear to occur through inhibition of L-type Ca(2+) channels,
      since I(sc) was unaffected by removal of extracellular Ca(2+). Verapamil also
      does not appear to inhibit I(sc) by modulating intracellular Ca(2+) stores, since
      it fails to inhibit transepithelial Na(+) transport when added to the basolateral
      side. The effect on Na(+) transport is specific for verapamil, since nifedipine,
      Ba(2+), 4-aminopyridine, and charybdotoxin do not significantly affect I(sc). A
      direct effect of verapamil on the epithelial Na(+) channel (ENaC) was tested
      using oocytes injected with the alpha-, beta-, and gamma-subunits. We conclude
      that verapamil inhibits transepithelial Na(+) transport in A6 cells by blocking
      ENaC and that the natriuresis observed with administration of verapamil may be
      due in part to its action on ENaC.

PMID- 12217869
TI  - Hyperosmotic urea activates basolateral NHE in proximal tubule from P-gp null and
      wild-type mice.
AB  - Using the pH-sensitive fluorescent dye BCECF, we compared the effects of
      hyperosmotic urea on basolateral Na(+)/H(+) exchange (NHE) with those of
      hyperosmotic mannitol in isolated nonperfused proximal tubule S2 segments from
      mice lacking both the mdr1a and mdr1b genes (KO) and wild-type (WT) mice. All the
      experiments were performed in CO(2)/HCO-free HEPES solutions. Osmolality of the
      peritubular solution was raised from 300 to 500 mosmol/kgH(2)O by adding mannitol
      or urea. NHE activity was assessed by the Na(+)-dependent acid extrusion rate
      (J(H)) after an acid load with NH(4)Cl prepulse. In WT mice, hyperosmotic
      mannitol had no effect on J(H) at over the entire range of intracellular pH
      (pH(i)) studied (6.20-6.90), whereas in KO mice it increased J(H) at a pH(i)
      range of 6.20-6.45. In contrast, in both WT and KO mice, hyperosmotic urea
      increased J(H) at a pH(i) range of 6.20-6.90. In KO mice, J(H) in a hyperosmotic
      urea solution were similar to those in a hyperosmotic mannitol solution at a
      pH(i) range of 6.20-6.40 but were greater than in a hyperosmotic mannitol
      solution at a pH(i) range of 6.45-6.90. In WT mice, hyperosmotic urea caused an
      increase in V(max) without changing K(m) for peritubular Na(+). Staurosporine
      (the PKC inhibitor) inhibited hyperosmotic mannitol-induced NHE activation in KO
      mice, whereas it had no effect on hyperosmotic urea-induced NHE activation in WT
      or KO mice. Genistein (the tyrosine kinase inhibitor) inhibited hyperosmotic urea
      induced NHE activation in WT and KO mice, whereas it caused no effect on
      hyperosmotic mannitol-induced NHE activation in KO mice. We conclude that
      hyperosmotic urea activates basolateral NHE via tyrosine kinase in tubules from
      both WT and KO mice, whereas hyperosmotic mannitol activates it via PKC only in
      tubules from KO mice.

PMID- 12217870
TI  - Protein kinase G activates inwardly rectifying K(+) channel in cultured human
      proximal tubule cells.
AB  - An ATP-regulated inwardly rectifying K(+) channel, whose activity is enhanced by
      PKA, is present in the plasma membrane of cultured human proximal tubule cells.
      In this study, we investigated the effects of PKG on this K(+) channel, using the
      patch-clamp technique. In cell-attached patches, bath application of a membrane
      permeant cGMP analog, 8-bromoguanosine 3',5'-monophosphate (8-BrcGMP; 100
      microM), stimulated channel activity, whereas application of a PKG-specific
      inhibitor, KT-5823 (1 microM), reduced the activity. Channel activation induced
      by 8-BrcGMP was observed even in the presence of a PKA-specific inhibitor, KT
      5720 (500 nM), which was abolished by KT-5823. Direct effects of cGMP and PKG
      were examined with inside-out patches in the presence of 1 mM MgATP. Although
      cytoplasmic cGMP (100 microM) alone had little effect on channel activity,
      subsequent addition of PKG (500 U/ml) enhanced it. Furthermore, bath application
      of atrial natriuretic peptide (ANP; 20 nM) in cell-attached patches stimulated
      channel activity, which was blocked by KT-5823. In conclusion, cGMP/PKG-dependent
      processes participate in activating the ATP-regulated K(+) channel and producing
      the stimulatory effect of ANP on channel activity.

PMID- 12217871
TI  - Rate of increase of osmolality determines osmotic tolerance of mouse inner
      medullary epithelial cells.
AB  - Renal inner medullary cells survive and function despite interstitial osmolality
      of 600-1,700 mosmol/kgH(2)O or more. In contrast, much smaller changes kill cells
      in tissue culture. Using mouse inner medullary epithelial cells at passage 2, we
      defined factors that might account for the difference. Most of the factors that
      we tested, including addition of hormones (insulin-like growth factor I,
      epidermal growth factor, or deamino-8-D-arginine vasopressin), growth on porous
      supports, and presence of matrix proteins (collagen I, collagen IV, fibronectin,
      laminin, or fibrillar collagen I), have no significant effect. However, the time
      course of the change makes a major difference. When osmolality is increased from
      640 to 1,640 mosmol/kgH(2)O by addition of NaCl and urea in a single step, only
      30% of cells survive for 24 h. However, when the same increase is made linearly
      over 20 h, 89% of the cells remain viable 24 h later. We conclude that gradual
      changes in osmolality, e.g., in vivo, allow cells to survive much greater changes
      than do the step changes routinely used in cell culture experiments.

PMID- 12217872
TI  - Metanephric mesenchyme contains embryonic renal stem cells.
AB  - Renal epithelial cells derive from either cells of the metanephric mesenchyme or
      ureteric bud cells, but the origin of other renal cells is unclear. To test
      whether metanephric mesenchymal cells generate cells other than epithelial, we
      examined the developmental potential of a metanephric mesenchymal cell line
      (7.1.1 cells) and of primary cultures of metanephric mesenchymal cells. 7.1.1
      Cells express both mesenchymal and epithelial markers and, on confluence, form
      well-defined monolayers expressing epithelial junctional proteins. However, 7.1.1
      cells as well as primary cultures of metanephric mesenchymal cells also generate
      spindle-shaped cells that are positive for alpha-smooth muscle actin, indicating
      that they are myofibroblasts and/or smooth muscle; this differentiation pathway
      is inhibited by collagen IV and enhanced by fetal calf serum or transforming
      growth factor-beta(1). Transforming growth factor-beta(1) also induces expression
      of smooth muscle proteins, indicating that the cells differentiate into smooth
      muscle. 7.1.1 Cells as well as primary cultures of metanephric mesenchymal cells
      also express vascular endothelial growth factor receptor 2 and Tie-2, suggesting
      that the metanephric mesenchymal cells that generate epithelia may also
      differentiate into endothelial cells. The pluripotency of the 7.1.1 cells is self
      renewing. The data suggest that the metanephric mesenchyme contains embryonic
      renal stem cells.

PMID- 12217873
TI  - Coordination of the cell cycle is an important determinant of the syndrome of
      acute renal failure.
AB  - Recovery from injury is usually accompanied by cell replication, in which new
      cells replace those irreparably damaged. After acute renal failure, normally
      quiescent kidney cells enter the cell cycle, which in tubule segments is
      accompanied by the induction of cell cycle inhibitors. We found that after acute
      renal failure induced by either cisplatin injection or renal ischemia, induction
      of the p21 cyclin-dependent kinase (cdk) inhibitor is protective. Mice lacking
      this gene developed more widespread kidney cell death, more severe renal failure,
      and had reduced survival, compared with mice with a functional p21 gene. Here, we
      show induction of 14-3-3sigma, a regulator of G(2)-to-M transition, after acute
      renal failure. Our findings, using both in vivo and in vitro models of acute
      renal failure, show that this protein likely helps to coordinate cell cycle
      activity to maximize recovery of renal epithelial cells from injury and reduce
      the extent of the injury itself. Because in terminally differentiated cells,
      these proteins are highly expressed only after injury, we propose that cell cycle
      coordination by induction of these proteins could be a general model of tissue
      recovery from stress and injury.

PMID- 12217874
TI  - Characterization of mouse urea transporters UT-A1 and UT-A2.
AB  - Specialized transporter proteins that are the products of two closely related
      genes, UT-A (Slc14a2) and UT-B (Slc14a1), modulate the movement of urea across
      cell membranes. The purpose of this study was to characterize the mouse variants
      of two major products of the UT-A gene, UT-A1 and UT-A2. Screening a mouse kidney
      inner medulla cDNA library yielded 4,047- and 2,876-bp cDNAs, the mouse
      homologues of UT-A1 and UT-A2. Northern blot analysis showed high levels of UT-A
      mRNAs in kidney medulla. UT-A transcripts were also present in testes, heart,
      brain, and liver. Immunoblots with an antiserum raised to the 19 COOH-terminal
      amino acids of rat UT-A1 (L194) identified immunoreactive proteins in kidney,
      testes, heart, brain, and liver and showed a complex pattern of differential
      expression. Relative to other tissues, kidney and brain had the highest levels of
      UT-A protein expression. In kidney sections, immunostaining with L194 revealed
      immunoreactive proteins in type 1 (short) and type 3 (long) thin descending limbs
      of the loop of Henle and in the middle and terminal inner medullary collecting
      ducts. Expression in Xenopus laevis oocytes showed that, characteristic of UT-A
      family members, the cDNAs encoded phloretin-inhibitable urea transporters. Acute
      application of PKA agonists (cAMP/forskolin/IBMX) caused a significant increase
      in UT-A1- and UT-A3-, but not UT-A2-mediated, urea transport.

PMID- 12217875
TI  - Molecular characterization of the murine Slc26a6 anion exchanger: functional
      comparison with Slc26a1.
AB  - We report the molecular and functional characterization of murine Slc26a6, the
      putative apical chloride-formate exchanger of the proximal tubule. The Slc26a6
      transcript is expressed in several tissues, including kidney. Alternative
      splicing of the second exon generates two distinct isoforms, denoted Slc26a6a and
      Slc26a6b, which differ in the inclusion of a 23-residue NH(2)-terminal extension.
      Functional comparison with murine Slc26a1, the basolateral oxalate exchanger of
      the proximal tubule, reveals a number of intriguing differences. Whereas Slc26a6
      is capable of Cl(-), SO, formate, and oxalate uptake when expressed in Xenopus
      laevis oocytes, Slc26a1 transports only SO and oxalate. Measurement of
      intracellular pH during the removal of extracellular Cl(-) in the presence and
      absence of HCO indicates that Slc26a6 functions as both a Cl(-)/HCO and a Cl(
      )/OH(-) exchanger; simultaneous membrane hyperpolarization during these
      experimental maneuvers reveals that HCO and OH(-) transport mediated by Slc26a6
      is electrogenic. Cis-inhibition and efflux experiments indicate that Slc26a6 can
      mediate the exchange of both Cl(-) and SOwith a number of substrates, including
      formate and oxalate. In contrast, SO and oxalate transport by Slc26a1 are
      mutually cis-inhibited but activated significantly by extracellular halides,
      lactate, and formate. The data indicate that Slc26a6 encodes an apical Cl(
      )/formate/oxalate and Cl(-)/base exchanger and reveal significant mechanistic
      differences between apical and basolateral oxalate exchangers of the proximal
      tubule.

PMID- 12217876
TI  - Regulation of kidney-specific Ksp-cadherin gene promoter by hepatocyte nuclear
      factor-1beta.
AB  - Kidney-specific cadherin (Ksp-cadherin) is a tissue-specific member of the
      cadherin family that is expressed exclusively in the kidney and developing
      genitourinary tract. Recent studies have shown that the proximal 250 bp of the
      Ksp-cadherin gene promoter are sufficient to direct tissue-specific gene
      expression in vivo and in vitro. The proximal 120 bp of the promoter are
      evolutionarily conserved between mouse and human and contain a DNase I
      hypersensitive site that is kidney cell specific. At position -55, the promoter
      contains a consensus recognition site for hepatocyte nuclear factor-1 (HNF-1).
      Mutations of the consensus HNF-1 site and downstream GC-boxes inhibit promoter
      activity in transfected cells. HNF-1alpha and HNF-1beta bind specifically to the 
      55 site, and both proteins transactivate the promoter directly. Expression of Ksp
      cadherin is not altered in the kidneys of HNF-1alpha-deficient mice. However,
      expression of a gain-of-function HNF-1beta mutant stimulates Ksp-cadherin
      promoter activity in transfected cells, whereas expression of a dominant-negative
      mutant inhibits activity. These studies identify Ksp-cadherin as the first kidney
      specific promoter that has been shown to be regulated by HNF-1beta. Mutations of
      HNF-1beta, as occur in humans with inherited renal cysts and diabetes, may cause
      dysregulated Ksp-cadherin promoter activity.

PMID- 12217877
TI  - Ca(2+) signaling and membrane potential in descending vasa recta pericytes and
      endothelia.
AB  - We devised a method for removal of pericytes from isolated descending vasa recta
      (DVR). After enzymatic digestion, aspiration of a descending vas rectum into a
      micropipette strips the pericytes from the abluminal surface. Pericytes and
      denuded endothelia can be recovered for separate study. Using fura 2-loaded
      preparations, we demonstrated that 10 nM angiotensin II (ANG II) elevates
      pericyte intracellular Ca(2+) concentration ([Ca(2+)](i)) and suppresses
      endothelial [Ca(2+)](i). The anion transport blocker probenecid helps retain fura
      2 in the pericyte cytoplasm. DVR endothelia were accessed for membrane potential
      measurement by perforated-patch whole cell recording by using the pericyte
      stripping technique and by turning nondigested vessels inside out with concentric
      micropipettes. By either method of access, 10 nM ANG II depolarized (n = 20) and
      100 nM bradykinin hyperpolarized (n = 25) the endothelia. We conclude that
      isolated endothelia and pericytes remain functional for study of [Ca(2+)](i)
      responses and that ANG II and bradykinin receptors exist separately on each cell
      type.

PMID- 12217878
TI  - Glycolysis as a metabolic marker in orthotopic breast cancer, monitored by in
      vivo (13)C MRS.
AB  - Enhanced glycolysis represents a striking feature of cancers and can therefore
      serve to indicate a malignant transformation. We have developed a noninvasive,
      quantitative method to characterize tumor glycolysis by monitoring (13)C-labeled
      glucose and lactate with magnetic resonance spectroscopy. This method was applied
      in MCF7 human breast cancer implanted in the mammary gland of female CD1-NU mice
      and was further employed to assess tumor response to hormonal manipulation with
      the antiestrogen tamoxifen. Analysis of the kinetic data based on a unique
      physiological-metabolic model yielded the rate parameters of glycolysis, glucose
      perfusion, and lactate clearance in the tumor, as well as glucose
      pharmacokinetics in the plasma. Treatment with tamoxifen induced a twofold
      reduction in the rate of glycolysis and of lactate clearance but did not affect
      the other parameters. This metabolic monitoring can thus serve to evaluate the
      efficacy of new selective estrogen receptor modulators and may be further
      extended to improve diagnosis and prognosis of breast cancer.

PMID- 12217879
TI  - Metabolic and anthropometric factors related to skeletal muscle UCP3 gene
      expression in healthy human adults.
AB  - This cross-sectional investigation sought to determine the relationship between
      selected metabolic, endocrine, and anthropometric factors and skeletal muscle
      UCP3 mRNA in healthy adult humans. Twenty-four healthy adults (13 male and 11
      female) across a range of aerobic capacity, age, and body composition were
      studied. Muscle biopsies were obtained from the vastus lateralis, from which UCP3
      mRNA was quantified by Northern blot, and fiber type was determined by use of the
      myosin ATPase staining procedure. In addition, resting energy expenditure and
      maximum rate of oxygen consumption were determined by indirect calorimetry, body
      composition was determined by dual-energy X-ray absorptiometry, and fasting
      plasma leptin and insulin were determined by ELISA. UCP3 mRNA was correlated
      positively with the percent type I fibers (r = 0.842, P < 0.001), plasma leptin
      (r = 0.454, P = 0.026), and plasma insulin (r = 0.615, P < 0.001) and inversely
      to age (r = -0.411, P = 0.046). Stepwise multiple regression analysis determined
      that percent type I muscle fibers was the best predictor of vastus lateralis UCP3
      mRNA, and no other variable entered the equation (model r(2) = 0.66). This study
      suggests that of the variables measured, UCP3 mRNA is primarily related to
      skeletal muscle fiber type in healthy adults. The factors that contribute to
      fiber-specific differences in UCP3 mRNA expression will need to be examined in
      future studies.

PMID- 12217880
TI  - Acute IGF-I infusion stimulates protein synthesis in skeletal muscle and other
      tissues of neonatal pigs.
AB  - Studies have shown that protein synthesis in skeletal muscle of neonatal pigs is
      uniquely sensitive to a physiological rise in both insulin and amino acids.
      Protein synthesis in cardiac muscle, skin, and spleen is responsive to insulin
      but not amino acid stimulation, whereas in the liver, protein synthesis responds
      to amino acids but not insulin. To determine the response of protein synthesis to
      insulin-like growth factor I (IGF-I) in this model, overnight-fasted 7- and 26
      day-old pigs were infused with IGF-I (0, 20, or 50 microg. kg(-1). h(-1)) to
      achieve levels within the physiological range, while amino acids and glucose were
      clamped at fasting levels. Because IGF-I infusion lowers circulating insulin
      levels, an additional group of high-dose IGF-I-infused pigs was also provided
      replacement insulin (10 ng. kg(-0.66). min(-1)). Tissue protein synthesis was
      measured using a flooding dose of L-[4-(3)H]phenylalanine. In 7-day-old pigs, low
      dose IGF-I increased protein synthesis by 25-60% in various skeletal muscles as
      well as in cardiac muscle (+38%), skin (+24%), and spleen (+32%). The higher dose
      of IGF-I elicited no further increase in protein synthesis above that found with
      the low IGF-I dose. Insulin replacement did not alter the response of protein
      synthesis to IGF-I in any tissue. The IGF-I-induced increases in tissue protein
      synthesis decreased with development. IGF-I infusion, with or without insulin
      replacement, had no effect on protein synthesis in liver, jejunum, pancreas, or
      kidney. Thus the magnitude, tissue specificity, and developmental change in the
      response of protein synthesis to acute physiological increases in plasma IGF-I
      are similar to those previously observed for insulin. This study provides in vivo
      data indicating that circulating IGF-I and insulin act on the same signaling
      components to stimulate protein synthesis and that this response is highly
      sensitive to stimulation in skeletal muscle of the neonate.

PMID- 12217881
TI  - Essential amino acids and muscle protein recovery from resistance exercise.
AB  - This study tests the hypothesis that a dose of 6 g of orally administered
      essential amino acids (EAAs) stimulates net muscle protein balance in healthy
      volunteers when consumed 1 and 2 h after resistance exercise. Subjects received a
      primed constant infusion of L-[(2)H(5)]phenylalanine and L-[1-(13)C]leucine.
      Samples from femoral artery and vein and biopsies from vastus lateralis were
      obtained. Arterial EAA concentrations increased severalfold after drinks. Net
      muscle protein balance (NB) increased proportionally more than arterial AA
      concentrations in response to drinks, and it returned rapidly to basal values
      when AA concentrations decreased. Area under the curve for net phenylalanine
      uptake above basal value was similar for the first hour after each drink (67 +/-
      17 vs. 77 +/- 20 mg/leg, respectively). Because the NB response was double the
      response to two doses of a mixture of 3 g of EAA + 3 g of nonessential AA (NEAA)
      (14), we conclude that NEAA are not necessary for stimulation of NB and that
      there is a dose-dependent effect of EAA ingestion on muscle protein synthesis.

PMID- 12217882
TI  - IGF-I attenuates diabetes-induced cardiac contractile dysfunction in ventricular
      myocytes.
AB  - Diabetic cardiomyopathy is characterized by impaired ventricular contraction and
      altered function of insulin-like growth factor I (IGF-I), a key factor for
      cardiac growth and function. Endogenous IGF-I has been shown to alleviate
      diabetic cardiomyopathy. This study was designed to evaluate exogenous IGF-I
      treatment on the development of diabetic cardiomyopathy. Adult rats were divided
      into four groups: control, control + IGF-I, diabetic, and diabetic + IGF-I.
      Streptozotocin (STZ; 55 mg/kg) was used to induce experimental diabetes
      immediately followed by a 7-wk IGF-I (3 mg. kg(-1). day(-1) ip) treatment.
      Mechanical properties were assessed in ventricular myocytes including peak
      shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)) and maximal
      velocities of shortening/relengthening (+/-dL/dt). Intracellular Ca(2+)
      transients were evaluated as Ca(2+)-induced Ca(2+) release and Ca(2+) clearing
      constant. Levels of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA),
      phospholamban (PLB), and glucose transporter (GLUT4) were assessed by Western
      blot. STZ caused significant weight loss and elevated blood glucose,
      demonstrating the diabetic status. The diabetic state is associated with reduced
      serum IGF-I levels, which were restored by IGF-I treatment. Diabetic myocytes
      showed reduced PS and +/-dL/dt as well as prolonged TPS, TR(90), and
      intracellular Ca(2+) clearing compared with control. IGF-I treatment prevented
      the diabetes-induced abnormalities in PS, +/-dL/dt, TR(90), and Ca(2+) clearing
      but not TPS. The levels of SERCA and GLUT4, but not PLB, were significantly
      reduced in diabetic hearts compared with controls. IGF-I treatment restored the
      diabetes-induced decline in SERCA, whereas it had no effect on GLUT4 and PLB
      levels. These results suggest that exogenous IGF-I treatment may ameliorate
      contractile disturbances in cardiomyocytes from diabetic animals and could
      provide therapeutic potential in the treatment of diabetic cardiomyopathy.

PMID- 12217883
TI  - Copper transport to mammary gland and milk during lactation in rats.
AB  - The delivery of copper to mammary gland and milk and the effects of lactation
      were examined in rats. Traces of (67)Cu/(64)Cu(II) were injected
      intraperitoneally or intravenously into virgin rats or lactating rats (2-5 days
      postpartum), and incorporation into blood, milk, and tissues was monitored. In
      virgin rats, most of the isotope first entered the liver and kidney. In lactating
      rats, almost 60% went directly to the mammary gland. Uptake rates and copper
      contents of the mammary gland were 20-fold higher in lactation. (67)Cu/(64)Cu
      appeared in milk and milk ceruloplasmin as rapidly as in mammary tissue and when
      there was no (67)Cu/(64)Cu-ceruloplasmin in the maternal plasma. Plasma (125)I
      labeled albumin entered milk much more slowly. Milk ceruloplasmin (10 mg/l) had
      25% of the (67)Cu/(64)Cu. Milk copper was 3.3 mg/l. Thus lactation markedly
      enhances the avidity of the mammary gland for copper, diverting most of it from
      liver and kidney to that tissue. Also, the primary source of milk ceruloplasmin
      is the mammary gland and not the maternal plasma.

PMID- 12217884
TI  - Upregulation of acyl-CoA: cholesterol acyltransferase in chronic renal failure.
AB  - Chronic renal failure (CRF) is associated with profound abnormalities of lipid
      metabolism and accelerated arteriosclerotic cardiovascular disease. In a recent
      study, we found marked downregulation of hepatic lecithin-cholesterol
      acyltransferase, or LCAT, expression, which can account for impaired HDL
      maturation and depressed HDL cholesterol concentration in CRF. Here, we report on
      the effect of CRF on acyl-CoA:cholesterol acyltransferase (ACAT) expression. ACAT
      is an intracellular enzyme that catalyzes esterification of free cholesterol to
      cholesterol ester for storage or secretion. ACAT plays a major role in hepatic
      production and release of VLDL, intestinal absorption of cholesterol, foam cell
      formation, and atherogenesis. We examined hepatic expression of ACAT-1 and ACAT-2
      mRNA (Northern blot) and protein (Western blot) abundance and total ACAT activity
      in male CRF rats (6 wk after 5/6 nephrectomy) and sham-operated controls. The CRF
      animals showed a significant reduction in creatinine clearance, marked
      hypertriglyceridemia, modest hypercholesterolemia, and significant upregulation
      of hepatic tissue ACAT-2 protein and mRNA abundance. In contrast, hepatic ACAT-1
      mRNA and protein abundance were unaffected by CRF. Upregulation of ACAT-2
      expression was accompanied by a significant increase in hepatic ACAT activity and
      a significant decrease in hepatic microsomal and whole liver free cholesterol
      concentration. Thus CRF results in significant upregulation of hepatic ACAT-2
      (but not ACAT-1) expression and ACAT activity, which may, in part, contribute to
      the associated lipid disorders.

PMID- 12217885
TI  - Free fatty acid-induced hepatic insulin resistance: a potential role for protein
      kinase C-delta.
AB  - The mechanisms of the impairment in hepatic glucose metabolism induced by free
      fatty acids (FFAs) and the importance of FFA oxidation in these mechanisms remain
      unclear. FFA-induced peripheral insulin resistance has been linked to membrane
      translocation of novel protein kinase C (PKC) isoforms, but the role of PKC in
      hepatic insulin resistance has not been assessed. To investigate the biochemical
      pathways that are induced by FFA in the liver and their relation to glucose
      metabolism in vivo, we determined endogenous glucose production (EGP), the
      hepatic content of citrate (product of acetyl-CoA derived from FFA oxidation and
      oxaloacetate), and hepatic PKC isoform translocation after 2 and 7 h Intralipid +
      heparin (IH) or SAL in rats. Experiments were performed in the basal state and
      during hyperinsulinemic clamps (insulin infusion rate, 5 mU. kg(-1). min(-1)). IH
      increased EGP in the basal state (P < 0.001) and during hyperinsulinemia (P <
      0.001) at 2 and 7 h. Also, 7-h infusion of IH induced resistance to the
      suppressive effect of insulin on EGP (P < 0.05). Glycerol infusion (resulting in
      plasma glycerol levels similar to IH infusion) did not have any effect on EGP. IH
      increased hepatic citrate content by twofold, independent of the insulin levels
      and the duration of IH infusion. IH induced hepatic PKC-delta translocation from
      the cytosolic to membrane fraction in all groups. PKC-delta translocation was
      greater at 7 compared with 2 h (P < 0.05). In conclusion, 1) increased FFA
      oxidation may contribute to the FFA-induced increase in EGP in the basal state
      and during hyperinsulinemia but is not associated with FFA-induced hepatic
      insulin resistance, and 2) the progressive insulin resistance induced by FFA in
      the liver is associated with a progressive increase in hepatic PKC-delta
      translocation.

PMID- 12217886
TI  - Regulation of the acid-labile subunit in sustained endotoxemia.
AB  - The effect of sustained endotoxemia on expression of the acid-labile subunit
      (ALS) in relation to hepatic markers of altered GH and insulin sensitivity was
      examined. Juvenile rats were injected with endotoxin twice daily for 48 h,
      causing reduced food intake and attenuated growth. In pair-fed controls, food
      restriction caused marked suppression of ALS gene expression and circulating
      levels within 12 h, and endotoxemia augmented this effect. This acute effect of
      endotoxin corresponded temporally with transient induction of suppressor of
      cytokine signaling (SOCS)-3, cytokine-inducible SH2-containing protein (CIS),
      phosphoenolpyruvate carboxykinase (PEPCK), and insulin-like growth factor-binding
      protein (IGFBP)-1 and suppression of GH receptor (GHR). During the subsequent 36
      h of sustained endotoxin treatment, expression of ALS recovered to, and then rose
      above, that of their pair-fed controls. This effect was paralleled by other
      ternary complex components. The inductive effect of sustained endotoxemia
      relative to pair-fed controls could not be explained by differences in expression
      of GHR, SOCS-3, or CIS but coincided with normalized PEPCK and IGFBP-1 levels,
      suggesting better hepatic insulin sensitivity in these animals. These data may
      indicate that, in sustained endotoxemia, ALS levels are regulated through
      modulation of hepatic insulin sensitivity.

PMID- 12217887
TI  - IGF-I does not affect the net increase in GH release in response to arginine.
AB  - Arginine stimulates growth hormone (GH) secretion, possibly by inhibiting
      hypothalamic somatostatin (SS) release. Insulin-like growth factor I (IGF-I)
      inhibits GH secretion via effects at the pituitary and/or hypothalamus. We
      hypothesized that if the dominant action of IGF-I is to suppress GH release at
      the level of the pituitary, then the arginine-induced net increase in GH
      concentration would be unaffected by an IGF-I infusion. Eight healthy young
      adults (3 women, 5 men) were studied on day 2 of a 47-h fast for 12 h (35th-47th
      h) on four occasions. Saline (Sal) or 10 microg. kg(-1). h(-1) recombinant human
      IGF-I was infused intravenously for 5 h from 37 to 42 h of the 47-h fast.
      Arginine (Arg) (30 g iv) or Sal was infused over 30 min during the IGF-I or Sal
      infusion from 40 to 40.5 h of the fast. Subjects received the following
      combinations of treatments in random order: 1) Sal + Sal; 2) Sal + Arg; 3) IGF-I
      + Sal; 4) IGF-I + Arg. Peak GH concentration on the IGF-I + Arg day was ~45% of
      that on the Sal + Arg day. The effect of arginine on net GH release was
      calculated as [(Sal + Arg) - (Sal + Sal)] - [(IGF-I + Arg) - (IGF-I + Sal)].
      There was no significant effect of IGF-I on net arginine-induced GH release over
      control conditions. These findings suggest that the negative feedback effect of
      IGF-I on GH secretion is primarily mediated at the pituitary level and/or at the
      hypothalamus through a mechanism different from the stimulatory effect of
      arginine.

PMID- 12217888
TI  - Estrogen effects on osmotic regulation of AVP and fluid balance.
AB  - To determine estrogen effects on osmotic regulation of arginine vasopressin (AVP)
      and body fluids, we suppressed endogenous estrogen and progesterone using the
      gonadotropin-releasing hormone (GnRH) analog leuprolide acetate (GnRHa). Subjects
      were assigned to one of two groups: 1) GnRHa alone, then GnRHa + estrogen (E, n =
      9, 25 +/- 1 yr); 2) GnRHa alone, then GnRHa + estrogen with progesterone (E/P, n
      = 6, 26 +/- 3). During GnRHa alone and with hormone treatment, we compared AVP
      and body fluid regulatory responses to 3% NaCl infusion (HSI, 120 min, 0.1 ml.
      min(-1). kg body wt(-1)), drinking (30 min, 15 ml/kg body wt), and recovery (60
      min of seated rest). Plasma [E(2)] increased from 23.9 to 275.3 pg/ml with
      hormone treatments. Plasma [P(4)] increased from 0.6 to 5.7 ng/ml during E/P and
      was unchanged (0.4 to 0.6 ng/ml) during E. Compared with GnRHa alone, E reduced
      osmotic AVP release threshold (275 +/- 4 to 271 +/- 4 mosmol/kg, P < 0.05), and
      E/P reduced the AVP increase in response during HSI (6.0 +/- 1.3 to 4.2 +/- 0.6
      pg/ml at the end of HSI), but free water clearance was unaffected in either
      group. Relative to GnRHa, pre-HSI plasma renin activity (PRA) was greater during
      E (0.8 +/- 0.1 vs. 1.2 +/- 0.2 ng ANG I. ml(-1). h(-1)) but not after HSI or
      recovery. PRA was greater than GnRHa during E/P at baseline (1.1 +/- 0.2 vs. 2.5
      +/- 0.6) and after HSI (0.6 +/- 0.1 vs. 1.1 +/- 1.1) and recovery (0.5 +/- 0.1
      vs. 1.3 +/- 0.2 ng ANG I. ml(-1). h(-1)). Baseline fractional excretion of sodium
      was unaffected by E or E/P but was attenuated by the end of recovery for both E
      (3.3 +/- 0.6 vs. 2.4 +/- 0.4%) and E/P (2.8 +/- 0.4 vs 1.7 +/- 0.4%, GnRHa alone
      and with hormone treatment, respectively). Fluid retention increased with both
      hormone treatments. Renal sensitivity to AVP may be lower during E due to
      intrarenal effects on water and sodium excretion. E/P increased sodium retention
      and renin-angiotensin-aldosterone stimulation.

PMID- 12217889
TI  - Thermal instability of rat muscle sarcoplasmic reticulum Ca(2+)-ATPase function.
AB  - To examine the thermal instability and the role of sulfhydryl (SH) oxidation on
      sarcoplasmic reticulum (SR) Ca(2+)-ATPase function, crude homogenates were
      prepared from the white portion of the gastrocnemius (WG) adult rat muscles (n =
      9) and incubated in vitro for < or =60 min either at a normal resting body
      temperature (37 degrees C) or at a temperature indicative of exercise-induced
      hyperthermia (41 degrees C) with DTT and without DTT (CON). In general, treatment
      with DTT resulted in higher Ca(2+)-ATPase and Ca(2+) uptake values (nmol. mg
      protein(-1). min(-1), P < 0.05), an effect that was not specific to time of
      incubation. Incubations at 41 degrees C resulted in lower (P < 0.05) Ca(2+)
      uptake rates (156 +/- 18 and 35.9 +/- 3.3) compared with 37 degrees C (570 +/- 54
      and 364 +/- 26) at 30 and 60 min, respectively. At 37 degrees C, ryanodine (300
      microM), which was used to block Ca(2+) release from the calcium release channel,
      prevented the time-dependent decrease in Ca(2+) uptake. A general inactivation (P
      < 0.05) of maximal Ca(2+)-ATPase activity (V(max)) in CON was observed with
      incubation time (0 > 30 > 60 min), with the effect being more pronounced (P <
      0.05) at 41 degrees C compared with 37 degrees C. The Hill slope, a measure of co
      operativity, and the pCa(50), the cytosolic Ca(2+) concentration required for
      half-maximal activation of Ca(2+)-ATPase activity, decreased (P < 0.05) at 41
      degrees C only. Treatment with DTT attenuated the alterations in enzyme kinetics.
      The increase in V(max) with the Ca(2+) ionophore A-23187 was less pronounced at
      41 degrees C compared with 37 degrees C. It is concluded that exposure of
      homogenates to a temperature typically experienced in exercise results in a
      reduction in the coupling ratio, which is mediated primarily by lower Ca(2+)
      uptake and occurs as a result of increases in membrane permeability to Ca(2+).
      Moreover, the decreases in Ca(2+)-ATPase kinetics in WG with sustained heat
      stress result from SH oxidation.

PMID- 12217890
TI  - Glitazones regulate glutamine metabolism by inducing a cellular acidosis in MDCK
      cells.
AB  - We studied the effect of the antihyperglycemic glitazones, ciglitazone,
      troglitazone, and rosiglitazone, on glutamine metabolism in renal tubule-derived
      Madin-Darby canine kidney (MDCK) cells. Troglitazone (25 microM) enhanced glucose
      uptake and lactate production by 108 and 92% (both P < 0.001). Glutamine
      utilization was not inhibited, but alanine formation decreased and ammonium
      formation increased (both P < 0.005). The decrease in net alanine formation
      occurred with a change in alanine aminotransferase (ALT) reactants, from close to
      equilibrium to away from equilibrium, consistent with inhibition of ALT activity.
      A shift of glutamine's amino nitrogen from alanine into ammonium was confirmed by
      using L-[2-(15)N]glutamine and measuring the [(15)N]alanine and [(15)N]ammonium
      production. The glitazone-induced shift from alanine to ammonium in glutamate
      metabolism was dose dependent, with troglitazone being twofold more potent than
      rosiglitazone and ciglitazone. All three glitazones induced a spontaneous
      cellular acidosis, reflecting impaired acid extrusion in responding to both an
      exogenous (NH) and an endogenous (lactic acid) load. Our findings are consistent
      with glitazones inducing a spontaneous cellular acidosis associated with a shift
      in glutamine amino nitrogen metabolism from predominantly anabolic into a
      catabolic pathway.

PMID- 12217891
TI  - Insufficient islet compensation to insulin resistance vs. reduced glucose
      effectiveness in glucose-intolerant mice.
AB  - This study evaluated the relative contribution of insulin-dependent mechanisms
      vs. mechanisms independent on dynamic insulin for glucose intolerance induced by
      high-fat diet. C57BL/6J mice underwent a frequently sampled intravenous glucose
      tolerance test (1 g/kg glucose) at 1 wk and 1, 3, and 10 mo after initiation of a
      high-fat diet (58% fat; control diet 11% fat) to measure glucose effectiveness
      (S(G)) and disposition index (DI), i.e., insulin sensitivity (S(I)) times early
      or total insulin secretion. Glucose disappearance (K(G)) and S(I) were reduced in
      high-fat-fed mice at all time points. Total (50 min) insulin secretion was
      sufficiently increased at all time points to compensate for the reduced S(I), as
      judged by normal DI(50) (min). In contrast, early (10 min) insulin secretion was
      not sufficiently increased; DI(10) (min) was reduced after 1, 3, and 10 mo. S(G)
      was reduced after 1 wk; the reduction persisted throughout the study period. Thus
      glucose intolerance induced by high-fat diet is, in early phases, solely
      explained by reduced glucose effectiveness, whereas insufficient early insulin
      secretion is of importance after long-term feeding.

PMID- 12217892
TI  - The long-acting GLP-1 derivative NN2211 ameliorates glycemia and increases beta
      cell mass in diabetic mice.
AB  - NN2211 is a long-acting, metabolically stable glucagon-like peptide-1 (GLP-1)
      derivative designed for once daily administration in humans. NN2211 dose
      dependently reduced the glycemic levels in ob/ob mice, with antihyperglycemic
      activity still evident 24 h postdose. Apart from an initial reduction in food
      intake, there were no significant differences between NN2211 and vehicle
      treatment, and body weight was not affected. Histological examination revealed
      that beta-cell proliferation and mass were not increased significantly in ob/ob
      mice with NN2211, although there was a strong tendency for increased
      proliferation. In db/db mice, exendin-4 and NN2211 decreased blood glucose
      compared with vehicle, but NN2211 had a longer duration of action. Food intake
      was lowered only on day 1 with both compounds, and body weight was unaffected.
      beta-Cell proliferation rate and mass were significantly increased with NN2211,
      but with exendin-4, only the beta-cell proliferation rate was significantly
      increased. In conclusion, NN2211 reduced blood glucose after acute and chronic
      treatment in ob/ob and db/db mice and was associated with increased beta-cell
      mass and proliferation in db/db mice. NN2211 is currently in phase 2 clinical
      development.

PMID- 12217893
TI  - Measurement of muscle protein fractional synthesis and breakdown rates from a
      pulse tracer injection.
AB  - We have developed a new method to determine the fractional synthesis rate (FSR)
      and breakdown rate (FBR) of muscle protein. This method involves a pulse tracer
      injection and measurement of enrichment in the arterial blood and muscle at three
      time points. The calculations of FSR and FBR are based on the precursor-product
      principle. To test this method, we gave a pulse injection of L-[ring
      (13)C(6)]phenylalanine of 4-6 mg/kg in five rabbits. The measured FBR value
      (0.233 +/- 0.060%/h) was almost identical (P = 0.35) to that (0.217 +/- 0.078%/h)
      estimated from a leg arteriovenous balance model (Biolo G, Chinkes D, Zhang X-J,
      and Wolfe RR. J Parenter Enteral Nutr 16: 305-315, 1992). The measured FSR value
      tended to be lower than that estimated from the leg model (0.125 +/- 0.036 vs.
      0.185 +/- 0.086%/h; P = 0.14), possibly because the new method measures only
      muscle FSR, whereas the leg balance model also includes skin and bone
      contributions. The pulse tracer injection did not affect muscle protein kinetics
      as measured by leucine and phenylalanine kinetics in the leg. In another five
      rabbits, we demonstrated that sampling could be reduced to either one or two
      muscle biopsies when multiple pulse injections were used. This method can be
      completed in 1 h with one muscle biopsy and has technical advantages over
      currently used methods.

PMID- 12217894
TI  - Cyr61 and CTGF are molecular markers of bladder wall remodeling after outlet
      obstruction.
AB  - Cysteine-rich protein (Cyr61) and connective tissue growth factor (CTGF) are key
      immediate early growth factors with functions in cell proliferation,
      differentiation, and extracellular matrix synthesis. Studies were performed to
      assess the gene expression profile of Cyr61 and CTGF in rat urinary bladder
      during growth in response to partial outlet obstruction. The mRNA levels of Cyr61
      as determined by ribonuclease protection assay increased sharply after 1 day and
      remained elevated throughout the time period of the obstruction. This correlates
      well with increased bladder weight. The CTGF mRNA levels seemed to peak within
      the second week of the urethral obstruction and correlate well with increased
      type I collagen mRNA. The expression pattern of either Cyr61 or CTGF proteins
      corroborated that of their respective mRNAs. Immunohistochemical analyses showed
      that immunoreactivity of Cyr61 was confined to detrusor smooth muscle and that of
      CTGF was detected within both detrusor muscle and lamina propria layers. These
      data strongly indicate the involvement of Cyr61 and CTGF in bladder wall
      remodeling as a result of the outlet obstruction.

PMID- 12217895
TI  - ADRP stimulates lipid accumulation and lipid droplet formation in murine
      fibroblasts.
AB  - Adipose differentiation-related protein (ADRP) is a lipid droplet-associated
      protein that is expressed early during adipose differentiation. The present study
      was undertaken to reveal the role of ADRP in adipose differentiation. In murine
      fibroblasts infected with green fluorescent protein (GFP)-ADRP fusion protein
      expression adenovirus vector, confocal microscopic analysis showed the number and
      size of lipid droplets apparently increased comparing with those of control
      cells. Overexpressed GFP-ADRP were mainly located at the surface of lipid
      droplets and appeared to be "ring-shaped." Triacylglycerol content was also
      significantly (P < 0.001) increased in GFP-ADRP-overexpressed cells compared with
      control cells. ADRP-induced lipid accumulation did not depend on adipocyte
      specific gene induction, such as peroxisome proliferator-activated receptor
      gamma, lipoprotein lipase, or other lipogenic genes, including acyl-CoA
      synthetase, fatty acid-binding protein, and fatty acid transporter. In
      conclusion, ADRP stimulated lipid accumulation and lipid droplet formation
      without induction of other adipocyte-specific genes or other lipogenic genes in
      murine fibroblasts. The detailed molecular mechanisms of ADRP on lipid
      accumulation remain to be elucidated.

PMID- 12217896
TI  - Glucose promotes pancreatic islet beta-cell survival through a PI 3-kinase/Akt
      signaling pathway.
AB  - The concentration of glucose in plasma is an important determinant of pancreatic
      beta-cell mass, whereas the relative contributions of hypertrophy, proliferation,
      and cell survival to this process are unclear. Glucose results in depolarization
      and subsequent calcium influx into islet beta-cells. Because depolarization and
      calcium (Ca(2+)) influx promote survival of neuronal cells, we hypothesized that
      glucose might alter survival of islet beta-cells through a similar mechanism. In
      the present studies, cultured mouse islet beta-cells showed a threefold decrease
      in apoptosis under conditions of 15 mM glucose compared with 2 mM glucose (P <
      0.05). MIN6 insulinoma cells incubated in 25 mM glucose for 24 h showed a
      threefold decrease in apoptosis compared with cells in 5 mM glucose (1.7 +/- 0.2
      vs. 6.3 +/- 1%, respectively, P < 0.001). High glucose (25 mM) enhanced survival
      required depolarization and Ca(2+) influx and was blocked by phosphatidylinositol
      (PI) 3-kinase inhibitors. Glucose activation of the protein kinase Akt was
      demonstrated in both insulinoma cells and cultured mouse islets by means of an
      antibody specific for Ser(473) phospho-Akt and by an in vitro Akt kinase assay.
      Akt phosphorylation was dependent on PI 3-kinase but not on MAPK. Transfection of
      insulinoma cells with an Akt kinase-dead plasmid (Akt-K179M) resulted in loss of
      glucose-mediated protection, whereas transfection with a constitutively active
      Akt enhanced survival in glucose-deprived insulinoma cells. The results of these
      studies defined a novel pathway for glucose-mediated activation of a PI 3
      kinase/Akt survival-signaling pathway in islet beta-cells. This pathway may
      provide important targets for therapeutic intervention.

PMID- 12217897
TI  - PTB-associated splicing factor regulates growth factor-stimulated gene expression
      in mammalian cells.
AB  - An insulin-like growth factor I (IGF-I) response element (IGFRE) in the porcine P
      450 cholesterol side-chain cleavage gene (P450scc) binds two transcription
      factors, Sp1 and polypyrimidine tract-binding protein-associated splicing factor
      (PSF). In this study, we investigated expression of these transcription factors
      in mouse Y1 adrenal cells, a cell line that does not increase P450scc expression
      in response to IGF-I. Western blot analysis showed a greater expression of PSF in
      Y1 cells when compared with a mouse fibroblast cell line (NWTb3) in which IGF-I
      stimulates the P450scc IGFRE. The two cell lines expressed Sp1 equally, and IGF-I
      did not increase expression of either transcription factor. Chromatin
      immunoprecipitation analysis with Y1 chromatin confirmed that PSF and Sp1 bound
      to the IGFRE. When increasing amounts of Sp1 were expressed in Y1 cells, the
      IGFRE became responsive to IGF-I. Moreover, a mutant oligonucleotide IGFRE
      reporter construct that lacks PSF binding was responsive to IGF-I. In conclusion,
      Y1 adrenal cells are a physiological example of PSF repression of growth factor
      stimulated (IGF-I) gene expression (P450scc). The dynamic nature of this
      repression is consistent with PSF functioning as a regulator of growth factor
      stimulated gene expression in mammalian cells.

PMID- 12217898
TI  - Behavioral, metabolic, and molecular correlates of lower insulin sensitivity in
      Mexican-Americans.
AB  - We determined whether lower insulin sensitivity persists in young, nonobese,
      nondiabetic Mexican-American [MA; n = 13, 27.0 +/- 2.0 yr, body mass index (BMI)
      23.0 +/- 0.7] compared with non-Hispanic white (NHW; n = 13, 24.8 +/- 1.5 yr, BMI
      22.8 +/- 0.6) males and females after accounting for cardiorespiratory fitness
      (maximal O(2) uptake), abdominal fat distribution (computed tomography scans),
      dietary intake (4-day records), and skeletal muscle insulin-signaling protein
      abundance from muscle biopsies (Western blot analysis). MA were significantly
      less insulin sensitive compared with their NHW counterparts when estimated by
      homeostatic model assessment of insulin resistance (MA: 1.53 +/- 0.22 vs. NHW:
      0.87 +/- 0.16, P < 0.05) and the revised quantitative insulin sensitivity check
      index (MA: 0.45 +/- 0.08 vs. NHW: 0.58 +/- 0.19, P = 0.05). However, skeletal
      muscle protein abundance of insulin receptor-beta (IRbeta), phosphatidylinositol
      3-kinase p85 subunit, Akt1, Akt2, and GLUT4 were not significantly different.
      Differences in indexes of insulin sensitivity lost significance after percent
      dietary intake of palmitic acid, palmitoleic acid, and skeletal muscle protein
      abundance of IRbeta were accounted for. We conclude that differences in insulin
      sensitivity between nonobese, nondiabetic MA and NHW persist after effects of
      chronic and acute exercise and total and abdominal fat distribution are accounted
      for. These differences may be mediated, in part, by dietary fat intake.

PMID- 12217899
TI  - S(G), S(I), and EGP of exercise-trained middle-aged men estimated by a two
      compartment labeled minimal model.
AB  - To examine the effects of physical training on glucose effectiveness (S(G)),
      insulin sensitivity (S(I)), and endogenous glucose production (EGP) in middle
      aged men, stable-labeled frequently sampled intravenous glucose tolerance tests
      (FSIGTT) were performed on 11 exercise-trained middle-aged men and 12 age-matched
      sedentary men. The time course of EGP during the FSIGTT was estimated by
      nonparametric stochastic deconvolution. Glucose uptake-specific indexes of
      glucose effectiveness (S(2*)(G) x 10(2): 0.81 +/- 0.08 vs. 0.60 +/- 0.05 dl. min(
      1). kg(-1), P < 0.05) and insulin sensitivity [S(2*)(I) x 10(4): 24.59 +/- 2.98
      vs. 11.89 +/- 2.36 dl. min(-1). (microU/ml)(-1). kg(-1), P < 0.01], which were
      analyzed using the two-compartment minimal model, were significantly greater in
      the trained group than in the sedentary group. Plasma clearance rate (PCR) of
      glucose was consistently greater in the trained men than in sedentary men
      throughout FSIGTT. Compared with sedentary controls, EGP of trained middle-aged
      men was higher before glucose load. The EGP of the two groups was similarly
      suppressed by approximately 70% within 10 min, followed by an additional
      suppression after insulin infusion. EGP returned to basal level at approximately
      60 min in the trained men and at 100 min in the controls, followed by its
      overshoot, which was significantly greater in the trained men than in the
      controls. In addition, basal EGP was positively correlated with S(2*)(G) . The
      higher basal EGP and greater EGP overshoot in trained middle-aged men appear to
      compensate for the increased insulin-independent (S(2*)(G)) and -dependent
      (S(2*)(I)) glucose uptake to maintain glucose homeostasis.

PMID- 12217900
TI  - Estrogen-induced osteogenesis in intact female mice lacking ERbeta.
AB  - We recently found that estrogen receptor (ER) antagonists prevent high-dose
      estrogen from inducing the formation of new cancellous bone within the medullary
      cavity of mouse long bones. In the present investigation, we studied the role of
      specific ER subtypes in this response by examining whether this is impaired in
      female ERbeta(-/-) mice previously generated by targeted gene deletion. Vehicle
      or 17beta-estradiol (E(2)) (range 4-4,000 microg. kg(-1). day(-1)) was
      administered to intact female ERbeta(-/-) mice and wild-type littermates by
      subcutaneous injection for 28 days. The osteogenic response was subsequently
      assessed by histomorphometry performed on longitudinal and cross sections of the
      tibia. E(2) was found to cause an equivalent increase in cancellous bone
      formation in ERbeta(-/-) mice and littermate controls, as assessed at the
      proximal and distal regions of the proximal tibial metaphysis. E(2) also resulted
      in a similar increase in endosteal mineral apposition rate in these two
      genotypes, as assessed at the tibial diaphysis. In contrast, cortical area in
      ERbeta(-/-) mice was found to be greater than that in wild types irrespective of
      E(2) treatment, as was tibial bone mineral density as measured by dual-energy X
      ray absorptiometry, consistent with previous reports of increased cortical bone
      mass in these animals. We conclude that, although ERbeta acts as a negative
      modulator of cortical modeling, this isoform does not appear to contribute to
      high-dose estrogen's ability to induce new cancellous bone formation in mouse
      long bones.

PMID- 12217901
TI  - Tissue-specific effects of chronic dietary leucine and norleucine supplementation
      on protein synthesis in rats.
AB  - Acute administration of leucine and norleucine activates the mammalian target of
      rapamycin (mTOR) cell-signaling pathway and increases rates of protein synthesis
      in a number of tissues in fasted rats. Although persistent stimulation of mTOR
      signaling is thought to increase protein synthetic capacity, little information
      is available concerning the effects of chronic administration of these agonists
      on protein synthesis, mTOR signal transduction, or leucine metabolism. Hence, we
      developed a model of chronic leucine/norleucine supplementation via drinking
      water and examined the effects of chronic (12 days) supplementation on protein
      synthesis in adipose tissue, kidney, heart, liver, and skeletal muscle from ad
      libitum-fed rats. The relative concentration of proteins involved in mTOR
      signaling and the two initial steps in leucine oxidation were also examined.
      Leucine or norleucine supplementation was accompanied by increased rates of
      protein synthesis in adipose tissue, liver, and skeletal muscle, but not in heart
      or kidney. Supplementation was not associated with increases in the anabolic
      hormones insulin or insulin-like growth factor I. Chronic supplementation did not
      cause apparent adaptation in either components of the mTOR cell-signaling pathway
      that respond to leucine (mTOR, ribosomal protein S6 kinase, and eukaryotic
      initiation factor 4E-binding protein-1) or the first two steps in leucine
      metabolism (the mitochondrial isoform of branched-chain amino acid transaminase,
      branched-chain keto acid dehydrogenase, and branched-chain keto acid
      dehydrogenase kinase), which may be involved in terminating the signal from
      leucine. These results suggest that provision of leucine or norleucine
      supplementation via the drinking water results in stimulation of postprandial
      protein synthesis in adipose tissue, skeletal muscle, and liver without notable
      adaptive changes in signaling proteins or metabolic enzymes.

PMID- 12217902
TI  - Physiological and pharmacological regulation of 20-kDa growth hormone.
AB  - The 20-kDa growth hormone (GH) is generated from alternative splicing of the
      primary transcript of full-length 22-kDa GH. We have studied the regulation of 20
      kDa GH over a range of pathophysiological conditions and in response to
      pharmacological stimulation using isoform-specific enzyme-linked immunosorbent
      assays (ELISAs). Mean 24-h levels of 20- and 22-kDa GH were higher in acromegaly
      and lower in GH deficiency than in normal subjects, with the 20-to-22-kDa ratio
      not different between the three groups. In normal subjects, 20-kDa GH was
      secreted in a pulsatile manner throughout the day, with peaks coinciding with
      those of 22-kDa GH. However, the half-life of 20-kDa GH (18.7 +/- 0.8 min) was
      significantly longer than that of 22-kDa GH (14.7 +/- 0.8 min; P < 0.02). Insulin
      induced hypoglycemia, androgen, and oral estrogen caused a parallel and
      proportionate increase in both isoforms. Octreotide suppressed 20-kDa less
      rapidly than 22-kDa GH in blood. Administration of recombinant 22-kDa GH in
      normal subjects rapidly reduced the 20-kDa GH levels. In conclusion, 20-kDa GH is
      cosecreted with and circulates at a constant proportion of 22-kDa GH. The 20-kDa
      GH level is reduced by administration of exogenous 22-kDa GH, suggesting rapid
      negative feedback regulation on pituitary release.

PMID- 12217903
TI  - Insulin signaling during perinatal liver development in the rat.
AB  - Insulin has long been assigned a key role in the regulation of growth and
      metabolism during fetal life. Our prior observations indicated that hepatic
      insulin signaling is attenuated in the late-gestation fetal rat. Therefore, we
      studied the perinatal ontogeny of hepatic insulin signaling extending from
      phosphatidylinositol 3-kinase (PI3K) to the ribosome. Initial studies
      demonstrated markedly decreased insulin-mediated activation of ribosomal protein
      S6 kinase 1 (S6K1) in the fetus. We found a similar pattern in the regulation of
      Akt, a kinase upstream from S6K1. Insulin produced minimal activation of insulin
      receptor substrate (IRS)-1-associated PI3K activity in fetal liver. A modest IRS
      2-associated response was seen in the fetus. However, levels of both IRS-1 and
      IRS-2 were very low in fetal liver relative to adult liver. IRS-1 content and
      insulin responsiveness of PI3K, Akt, and S6K1 showed a transition to the adult
      phenotype during the first several postnatal weeks. Examination of downstream
      insulin signaling to the translational apparatus showed marked attenuation,
      relative to the adult, of fetal hepatic insulin-mediated phosphorylation of 4E
      BP1, the regulatory protein for the eukaryotic initiation factor eIF4E, and
      ribosomal protein S6. The mammalian target of rapamycin (mTOR), a key integrator
      of nutritional and metabolic regulation of translation, was present in low
      amounts, was hypophosphorylated, and was not insulin sensitive in the fetus. Our
      results indicate that protein synthesis during late-gestation liver development
      may be mTOR and insulin independent. Reexamination of the role of insulin in
      fetal liver physiology may be warranted.

PMID- 12217904
TI  - Insulin increases branched-chain alpha-ketoacid dehydrogenase kinase expression
      in Clone 9 rat cells.
AB  - The branched-chain amino acids (BCAA) are committed to catabolism by the activity
      of the branched-chain alpha-ketoacid dehydrogenase (BCKD) complex. BCKD activity
      is regulated through the action of the complex-specific BCKD kinase that
      phosphorylates two serine residues in the E1alpha subunit. Greater BCKD kinase
      expression levels result in a lower activity state of BCKD and thus a decreased
      rate of BCAA catabolism. Activity state varies among tissues and can be altered
      by diet, exercise, hormones, and disease state. Within individual tissues, the
      concentration of BCKD kinase reflects the activity state of the BCKD complex.
      Here we investigated the effects of insulin, an important regulator of hepatic
      metabolic enzymes, on BCKD kinase expression in Clone 9 rat cells. Insulin
      effected a twofold increase in message levels and a twofold increase in BCKD
      kinase protein levels. The response was completely blocked by treatment with LY
      294002 and partially blocked by rapamycin, thus demonstrating a dependence on
      phosphatidylinositol 3-kinase and mTOR function, respectively. These studies
      suggest that insulin acts to regulate BCAA catabolism through stimulation of BCKD
      kinase expression.

PMID- 12217905
TI  - Adiponectin is not altered with exercise training despite enhanced insulin
      action.
AB  - Adiponectin is an adipocytokine that is hypothesized to be involved in the
      regulation of insulin action. The purpose of the present investigation was to
      determine whether plasma adiponectin is altered in conjunction with enhanced
      insulin action with exercise training. An insulin sensitivity index (S(I)) and
      fasting levels of glucose, insulin, and adiponectin were assessed before and
      after 6 mo of exercise training (4 days/wk for approximately 45 min at 65-80%
      peak O(2) consumption) with no loss of body mass (PRE, 91.9 +/- 3.8 kg vs. POST,
      91.6 +/- 3.9 kg) or fat mass (PRE, 26.5 +/- 1.8 kg vs. POST, 26.7 +/- 2.2 kg).
      Insulin action significantly (P < 0.05) improved with exercise training (S(I)
      +98%); however, plasma adiponectin concentration did not change (PRE, 6.3 +/- 1.5
      microg/ml vs. POST, 6.6 +/- 1.8 microg/ml). In contrast, in a separate group of
      subjects examined before and after weight loss, there was a substantial increase
      in adiponectin (+281%), which was accompanied by enhanced insulin action (S(I),
      +432%). These data suggest that adiponectin is not a contributory factor to the
      exercise-related improvements in insulin sensitivity.

PMID- 12217906
TI  - Genome structures embossed by oligonucleotide-stickiness.
AB  - MOTIVATION: An unmanageably large amount of data on genome sequences is
      accumulating, prompting researchers to develop new methods to analyze them. We
      have devised a novel method designated oligostickiness, a measure roughly
      proportional to the binding affinity of an oligonucleotide to a DNA of interest,
      in order to analyze genome sequences as a whole. RESULTS: Fifteen representative
      genomes such as Bacillus subtilis, Escherichia coli, Saccharomyces cerevisiae,
      Caenorhabditis elegans, H. sapiens and others were analyzed by this method using
      more than 50 probe dodecanucleotides, offering the following findings: (i) Genome
      sequences can be specifically featured by way of oligostickiness maps. (ii)
      Oligostickiness analysis, which is similar to but more informative than (G + C)
      content or repetitive sequence analysis, can reveal intra-genomic structures such
      as mosaic structures (E. coli and B. subtilis) and highly sticky/non-sticky
      regions of biological meanings. (iii) Some probe oligonucleotides such as dC(12)
      and dT(12) can be used for classifying genomes, clearly discriminating
      prokaryotes and eukaryotes. (iv) Based on global oligostickiness, which is the
      average value of the local oligostickinesses, the features of a genome could be
      visualized in spider web mode. The pattern of a spider web as well as a set of
      oligostickiness maps is highly characteristic to each genome or chromosome. Thus,
      we called it as chromosome texture, leading to a finding that all the chromosomes
      contained in a cell, so far investigated, have a common texture. AVAILABILITY:
      Oligostickinesses maps used in this work are available at http://gp.fms.saitama
      u.ac.jp/ CONTACT: koichi@fms.saitama-u.ac.jp

PMID- 12217907
TI  - Pooled library tissue tags for EST-based gene discovery.
AB  - MOTIVATION: In gene discovery projects based on EST sequencing, effective post
      sequencing identification methods are important in determining tissue sources of
      ESTs within pooled cDNA libraries. In the past, such identification efforts have
      been characterized by higher than necessary failure rates due to the presence of
      errors within the subsequence containing the oligo tag intended to define the
      tissue source for each EST. RESULTS: A large-scale EST-based gene discovery
      program at The University of Iowa has led to the creation of a unique software
      method named UITagCreator usable in the creation of large sets of synthetic
      tissue identification tags. The identification tags provide error detection and
      correction capability and, in conjunction with automated annotation software,
      result in a substantial improvement in the accurate identification of the tissue
      source in the presence of sequencing and base-calling errors. These
      identification rates are favorable, relative to past paradigms. AVAILABILITY: The
      UITagCreator source code and installation instructions, along with detection
      software usable in concert with created tag sets, is freely available at
      http://genome.uiowa.edu/pubsoft/software.html CONTACT: tomc@eng.uiowa.edu

PMID- 12217908
TI  - Identification of regulatory elements using a feature selection method.
AB  - MOTIVATION: Many methods have been described to identify regulatory motifs in the
      transcription control regions of genes that exhibit similar patterns of gene
      expression across a variety of experimental conditions. Here we focus on a single
      experimental condition, and utilize gene expression data to identify sequence
      motifs associated with genes that are activated under this experimental
      condition. We use a linear model with two-way interactions to model gene
      expression as a function of sequence features (words) present in presumptive
      transcription control regions. The most relevant features are selected by a
      feature selection method called stepwise selection with monte carlo cross
      validation. We apply this method to a publicly available dataset of the yeast
      Saccharomyces cerevisiae, focussing on the 800 basepairs immediately upstream of
      each gene's translation start site (the upstream control region (UCR)). RESULTS:
      We successfully identify regulatory motifs that are known to be active under the
      experimental conditions analyzed, and find additional significant sequences that
      may represent novel regulatory motifs. We also discuss a complementary method
      that utilizes gene expression data from a single microarray experiment and allows
      averaging over variety of experimental conditions as an alternative to motif
      finding methods that act on clusters of co-expressed genes. AVAILABILITY: The
      software is available upon request from the first author or may be downloaded
      from http://www.stat.berkeley.edu/~sunduz. CONTACT: keles@stat.berkeley.edu

PMID- 12217909
TI  - Geometry of gene expression dynamics.
AB  - MOTIVATION: A gene expression trajectory moves through a high dimensional space
      where each axis represents the mRNA abundance of a different gene. Genome wide
      gene expression has a dynamic structure, especially in studies of development and
      temporal response. Both visualization and analyses of such data require an
      explicit attention to the temporal structure. RESULTS: Using three cell cycle
      trajectories from Saccharomyces cerevisiae to illustrate, we present several
      techniques which reveal the geometry of the data. We import phase-delay time
      plots from chaotic systems theory as a dynamic data visualization device and show
      how these plots capture important aspects of the trajectories. We construct an
      objective function to find an optimal two-dimensional projection of the cell
      cycle, demonstrate that the system returns to this plane after three different
      initial perturbations, and explore the conditions under which this geometric
      approach outperforms standard approaches such as singular value decomposition and
      Fourier analysis. Finally, we show how a geometric analysis can isolate distinct
      parts of the trajectories, in this case the initial perturbation versus the cell
      cycle. CONTACT: junhyong.kim@yale.edu

PMID- 12217910
TI  - Determination of minimum sample size and discriminatory expression patterns in
      microarray data.
AB  - MOTIVATION: Transcriptional profiling using microarrays can reveal important
      information about cellular and tissue expression phenotypes, but these
      measurements are costly and time consuming. Additionally, tissue sample
      availability poses further constraints on the number of arrays that can be
      analyzed in connection with a particular disease or state of interest. It is
      therefore important to provide a method for the determination of the minimum
      number of microarrays required to separate, with statistical reliability,
      distinct disease states or other physiological differences. RESULTS: Power
      analysis was applied to estimate the minimum sample size required for two-class
      and multi-class discrimination. The power analysis algorithm calculates the
      appropriate sample size for discrimination of phenotypic subtypes in a reduced
      dimensional space obtained by Fisher discriminant analysis (FDA). This approach
      was tested by applying the algorithm to existing data sets for estimation of the
      minimum sample size required for drawing certain conclusions on multi-class
      distinction with statistical reliability. It was confirmed that when the minimum
      number of samples estimated from power analysis is used, group means in the FDA
      discrimination space are statistically different. CONTACT: gregstep@mit.edu

PMID- 12217911
TI  - Bayesian infinite mixture model based clustering of gene expression profiles.
AB  - MOTIVATION: The biologic significance of results obtained through cluster
      analyses of gene expression data generated in microarray experiments have been
      demonstrated in many studies. In this article we focus on the development of a
      clustering procedure based on the concept of Bayesian model-averaging and a
      precise statistical model of expression data. RESULTS: We developed a clustering
      procedure based on the Bayesian infinite mixture model and applied it to
      clustering gene expression profiles. Clusters of genes with similar expression
      patterns are identified from the posterior distribution of clusterings defined
      implicitly by the stochastic data-generation model. The posterior distribution of
      clusterings is estimated by a Gibbs sampler. We summarized the posterior
      distribution of clusterings by calculating posterior pairwise probabilities of co
      expression and used the complete linkage principle to create clusters. This
      approach has several advantages over usual clustering procedures. The analysis
      allows for incorporation of a reasonable probabilistic model for generating data.
      The method does not require specifying the number of clusters and resulting
      optimal clustering is obtained by averaging over models with all possible numbers
      of clusters. Expression profiles that are not similar to any other profile are
      automatically detected, the method incorporates experimental replicates, and it
      can be extended to accommodate missing data. This approach represents a
      qualitative shift in the model-based cluster analysis of expression data because
      it allows for incorporation of uncertainties involved in the model selection in
      the final assessment of confidence in similarities of expression profiles. We
      also demonstrated the importance of incorporating the information on experimental
      variability into the clustering model. AVAILABILITY: The MS Windows(TM) based
      program implementing the Gibbs sampler and supplemental material is available at
      http://homepages.uc.edu/~medvedm/BioinformaticsSupplement.htm CONTACT:
      medvedm@email.uc.edu

PMID- 12217912
TI  - Ratio statistics of gene expression levels and applications to microarray data
      analysis.
AB  - MOTIVATION: Expression-based analysis for large families of genes has recently
      become possible owing to the development of cDNA microarrays, which allow
      simultaneous measurement of transcript levels for thousands of genes. For each
      spot on a microarray, signals in two channels must be extracted from their
      backgrounds. This requires algorithms to extract signals arising from tagged mRNA
      hybridized to arrayed cDNA locations and algorithms to determine the significance
      of signal ratios. RESULTS: This paper focuses on estimation of signal ratios from
      the two channels, and the significance of those ratios. The key issue is the
      determination of whether a ratio is significantly high or low in order to
      conclude whether the gene is upregulated or downregulated. The paper builds on an
      earlier study that involved a hypothesis test based on a ratio statistic under
      the supposition that the measured fluorescent intensities subsequent to image
      processing can be assumed to reflect the signal intensities. Here, a refined
      hypothesis test is considered in which the measured intensities forming the ratio
      are assumed to be combinations of signal and background. The new method involves
      a signal-to-noise ratio, and for a high signal-to-noise ratio the new test
      reduces (with close approximation) to the original test. The effect of low signal
      to-noise ratio on the ratio statistics constitutes the main theme of the paper.
      Finally, and in this vein, a quality metric is formulated for spots. This measure
      can be used to decide whether or not a spot ratio should be deleted, or to adjust
      various measurements to reflect confidence in the quality of the measurement.
      CONTACT: e-dougherty@tamu.edu

PMID- 12217913
TI  - Multi-class cancer classification via partial least squares with gene expression
      profiles.
AB  - MOTIVATION: Discrimination between two classes such as normal and cancer samples
      and between two types of cancers based on gene expression profiles is an
      important problem which has practical implications as well as the potential to
      further our understanding of gene expression of various cancer cells.
      Classification or discrimination of more than two groups or classes (multi-class)
      is also needed. The need for multi-class discrimination methodologies is apparent
      in many microarray experiments where various cancer types are considered
      simultaneously. RESULTS: Thus, in this paper we present the extension to the
      classification methodology proposed earlier Nguyen and Rocke (2002b;
      Bioinformatics, 18, 39-50) to classify cancer samples from multiple classes. The
      methodologies proposed in this paper are applied to four gene expression data
      sets with multiple classes: (a) a hereditary breast cancer data set with (1)
      BRCA1-mutation, (2) BRCA2-mutation and (3) sporadic breast cancer samples, (b) an
      acute leukemia data set with (1) acute myeloid leukemia (AML), (2) T-cell acute
      lymphoblastic leukemia (T-ALL) and (3) B-cell acute lymphoblastic leukemia (B
      ALL) samples, (c) a lymphoma data set with (1) diffuse large B-cell lymphoma
      (DLBCL), (2) B-cell chronic lymphocytic leukemia (BCLL) and (3) follicular
      lymphoma (FL) samples, and (d) the NCI60 data set with cell lines derived from
      cancers of various sites of origin. In addition, we evaluated the classification
      algorithms and examined the variability of the error rates using simulations
      based on randomization of the real data sets. We note that there are other
      methods for addressing multi-class prediction recently and our approach is along
      the line of Nguyen and Rocke (2002b; Bioinformatics, 18, 39-50). CONTACT:
      dnguyen@stat.tamu.edu; dmrocke@ucdavis.edu

PMID- 12217914
TI  - Optimal enhancement of immune response.
AB  - MOTIVATION: Therapeutic enhancement of innate immune response to microbial attack
      is addressed as the optimal control of a dynamic system. Interactions between an
      invading pathogen and the innate immune system are characterized by four non
      linear, ordinary differential equations that describe rates of change of
      pathogen, plasma cell, and antibody concentrations, and of an indicator of
      organic health. Without therapy, the dynamic model evidences sub-clinical or
      clinical decay, chronic stabilization, or unrestrained lethal growth of the
      pathogen; the response pattern depends on the initial concentration of pathogens
      in the simulated attack. In the model, immune response can be augmented by
      therapeutic agents that kill the pathogen directly, that stimulate the production
      of plasma cells or antibodies, or that enhance organ health. A previous paper
      demonstrated open-loop optimal control solutions that defeat the pathogen and
      preserve organ health, given initial conditions that otherwise would be lethal
      (Stengel et al. (2002)). Therapies based on separate and combined application of
      the agents were derived by minimizing a quadratic cost function that weighted
      both system response and control usage, providing implicit control over harmful
      side effects. RESULTS: We demonstrate the ability of neighboring-optimal feedback
      control to account for a range of unknown initial conditions and persistent input
      of pathogens by adjusting the therapy to account for perturbations from the
      nominal-optimal response history. We examine therapies that combine open-loop
      control of one agent with closed-loop control of another. We show that optimal
      control theory points the way toward new protocols for treatment and cure of
      human diseases. CONTACT: stengel@princeton.edu; rghiglia@princeton.edu;
      nkulkarn@princeton.edu

PMID- 12217915
TI  - The correlation error and finite-size correction in an ungapped sequence
      alignment.
AB  - MOTIVATION: The BLAST program for comparing two sequences assumes independent
      sequences in its random model. The resulting random alignment matrices have
      correlations across their diagonals. Analytic formulas for the BLAST p-value
      essentially neglect these correlations and are equivalent to a random model with
      independent diagonals. Progress on the independent diagonals model has been
      surprisingly rapid, but the practical magnitude of the correlations it neglects
      remains unknown. In addition, BLAST uses a finite-size correction that is
      particularly important when either of the sequences being compared is short.
      Several formulas for the finite-size correction have now been given, but the
      corresponding errors in the BLAST p-values have not been quantified. As the
      lengths of compared sequences tend to infinity, it is also theoretically unknown
      whether the neglected correlations vanish faster than the finite-size correction.
      RESULTS: Because we required certain analytic formulas, our study restricted its
      computer experiments to ungapped sequence alignment. We expect some of our
      conclusions to extend qualitatively to gapped sequence alignment, however. With
      this caveat, the finite-size correction appeared to vanish faster than the
      neglected correlations. Although the finite-size correction underestimated the
      BLAST p-value, it improved the approximation substantially for all but very short
      sequences. In practice, the Altschul-Gish finite-size correction was superior to
      Spouge's. The independent diagonals model was always within a factor of 2 of the
      true BLAST p-value, although fitting p-value parameters from it probably is
      unwise. CONTACT: spouge@ncbi.nlm.nih.gov

PMID- 12217916
TI  - The use of structure information to increase alignment accuracy does not aid
      homologue detection with profile HMMs.
AB  - MOTIVATION: The best quality multiple sequence alignments are generally
      considered to derive from structural superposition. However, no previous work has
      studied the relative performance of profile hidden Markov models (HMMs) derived
      from such alignments. Therefore several alignment methods have been used to
      generate multiple sequence alignments from 348 structurally aligned families in
      the HOMSTRAD database. The performance of profile HMMs derived from the
      structural and sequence-based alignments has been assessed for homologue
      detection. RESULTS: The best alignment methods studied here correctly align
      nearly 80% of residues with respect to structure alignments. Alignment quality
      and model sensitivity are found to be dependent on average number, length, and
      identity of sequences in the alignment. The striking conclusion is that, although
      structural data may improve the quality of multiple sequence alignments, this
      does not add to the ability of the derived profile HMMs to find sequence
      homologues. SUPPLEMENTARY INFORMATION: A list of HOMSTRAD families used in this
      study and the corresponding Pfam families is available at
      http://www.sanger.ac.uk/Users/sgj/alignments/map.html CONTACT: sgj@sanger.ac.uk

PMID- 12217917
TI  - ESyPred3D: Prediction of proteins 3D structures.
AB  - MOTIVATION: Homology or comparative modeling is currently the most accurate
      method to predict the three-dimensional structure of proteins. It generally
      consists in four steps: (1) databanks searching to identify the structural
      homolog, (2) target-template alignment, (3) model building and optimization, and
      (4) model evaluation. The target-template alignment step is generally accepted as
      the most critical step in homology modeling. RESULTS: We present here ESyPred3D,
      a new automated homology modeling program. The method gets benefit of the
      increased alignment performances of a new alignment strategy. Alignments are
      obtained by combining, weighting and screening the results of several multiple
      alignment programs. The final three-dimensional structure is build using the
      modeling package MODELLER. ESyPred3D was tested on 13 targets in the CASP4
      experiment (Critical Assessment of Techniques for Proteins Structural
      Prediction). Our alignment strategy obtains better results compared to PSI-BLAST
      alignments and ESyPred3D alignments are among the most accurate compared to those
      of participants having used the same template. AVAILABILITY: ESyPred3D is
      available through its web site at http://www.fundp.ac.be/urbm/bioinfo/esypred/
      CONTACT: christophe.lambert@fundp.ac.be; http://www.fundp.ac.be/~lambertc

PMID- 12217918
TI  - A dissimilarity matrix between protein atom classes based on Gaussian mixtures.
AB  - MOTIVATION: Previously, Rantanen et al. (2001; J. Mol. Biol., 313, 197-214)
      constructed a protein atom-ligand fragment interaction library embodying
      experimentally solved, high-resolution three-dimensional (3D) structural data
      from the Protein Data Bank (PDB). The spatial locations of protein atoms that
      surround ligand fragments were modeled with Gaussian mixture models, the
      parameters of which were estimated with the expectation-maximization (EM)
      algorithm. In the validation analysis of this library, there was strong
      indication that the protein atom classification, 24 classes, was too large and
      that a reduction in the classes would lead to improved predictions. RESULTS:
      Here, a dissimilarity (distance) matrix that is suitable for comparison and
      fusion of 24 pre-defined protein atom classes has been derived. Jeffreys'
      distances between Gaussian mixture models are used as a basis to estimate
      dissimilarities between protein atom classes. The dissimilarity data are analyzed
      both with a hierarchical clustering method and independently by using
      multidimensional scaling analysis. The results provide additional insight into
      the relationships between different protein atom classes, giving us guidance on,
      for example, how to readjust protein atom classification and, thus, they will
      help us to improve protein--ligand interaction predictions. CONTACT: vira@utu.fi

PMID- 12217919
TI  - VIZARD: analysis of Affymetrix Arabidopsis GeneChip data.
AB  - The Affymetrix GeneChip Arabidopsis genome array has proved to be a very powerful
      tool for the analysis of gene expression in Arabidopsis thaliana, the most
      commonly studied plant model organism. VIZARD is a Java program created at the
      University of California, Berkeley, to facilitate analysis of Arabidopsis
      GeneChip data. It includes several integrated tools for filtering, sorting,
      clustering and visualization of gene expression data as well as tools for the
      discovery of regulatory motifs in upstream sequences. VIZARD also includes
      annotation and upstream sequence databases for the majority of genes represented
      on the Affymetrix Arabidopsis GeneChip array. AVAILABILITY: VIZARD is available
      free of charge for educational, research, and not-for-profit purposes, and can be
      downloaded at http://www.anm.f2s.com/research/vizard/ CONTACT:
      moseyko@uclink4.berkeley.edu

PMID- 12217920
TI  - SEGE: A database on 'intron less/single exonic' genes from eukaryotes.
AB  - Eukaryotes have both 'intron containing' and 'intron less' genes. Several
      databases are available for 'intron containing' genes in eukaryotes. In this
      note, we describe a database for 'intron less' genes from eukaryotes. 'Intron
      less' eukaryotic genes having prokaryotic architecture will help to understand
      gene evolution in a much simpler way unlike 'intron containing' genes.
      AVAILABILITY: SEGE is available at http://intron.bic.nus.edu.sg/seg/ CONTACT:
      mmeena@ntu.edu.sg

PMID- 12217921
TI  - UniBLAST: a system to filter, cluster, and display BLAST results and assign
      unique gene annotation.
AB  - MOTIVATION: More and more often, a gene is epitomized by a large number of
      sequences in GenBank. This high redundancy makes it very difficult to identify a
      unique best match for a query sequence from its BLAST results. We developed a
      novel program UniBLAST that filters out uninformative hits, clusters the
      redundant hits, groups the hits by LocusLink, and graphically displays the
      results. We also implemented a scoring function in UniBLAST to assign a unique
      gene name to a query sequence. UniBLAST significantly increases the efficiency of
      gene annotation. AVAILABILITY: The program is available at
      http://south.genomics.org.cn/software/uniblast/index.html CONTACT:
      uniblast@genomics.org.cn; wei@nexusgenomics.com

PMID- 12217922
TI  - Parallelized multiple alignment.
AB  - Multiple sequence alignment is a frequently used technique for analyzing sequence
      relationships. Compilation of large alignments is computationally expensive, but
      processing time can be considerably reduced when the computational load is
      distributed over many processors. Parallel processing functionality in the form
      of single-instruction multiple-data (SIMD) technology was implemented into the
      multiple alignment program Praline by using 'message passing interface' (MPI)
      routines. Over the alignments tested here, the parallelized program performed up
      to ten times faster on 25 processors compared to the single processor version.
      AVAILABILITY: Example program code for parallelizing pairwise alignment loops is
      available from http://mathbio.nimr.mrc.ac.uk/~jkleinj/tools/mpicode. The 'message
      passing interface' package (MPICH) is available from
      http:/www.unix.mcs.anl.gov/mpi/mpich. CONTACT: jhering@nimr.mrc.ac.uk
      SUPPLEMENTARY INFORMATION: Praline is accessible at
      http://mathbio.nimr.mrc.ac.uk/praline.

PMID- 12217923
TI  - OrthoGUI: graphical presentation of Orthostrapper results.
AB  - SUMMARY: Orthostrapper is a program that calculates orthology support values for
      pairs of sequences in a multiple alignment (Storm and Sonnhammer, Bioinformatics,
      18, 92-99, 2002). Here we present OrthoGUI, a web interface and display tool for
      Orthostrapper analysis. OrthoGUI visualizes the Orthostrapper output in both
      tabular and tree representations, and can also apply a clustering algorithm to
      identify groups of multiple orthologs, which are indicated by colour coding.
      AVAILABILITY: http://www.cgb.ki.se/OrthoGUI CONTACT: erik.sonnhammer@cgb.ki.se

PMID- 12217924
TI  - A kinase sequence database: sequence alignments and family assignment.
AB  - The Kinase Sequence Database (KSD) located at http://kinase.ucsf.edu/ksd contains
      information on 290 protein kinase families derived by profile-based clustering of
      the non-redundant list of sequences obtained from a GenBank-wide search. Included
      in the database are a total of 5,041 protein kinases from over 100 organisms.
      Clustering into families is based on the extent of homology within the kinase
      catalytic domain (250-300 residues in length). Alignments of the families are
      viewed by interactive Excel-based sequence spreadsheets. In addition, KSD
      features evolutionary trees derived for each family and detailed information on
      each sequence as well as links to the corresponding GenBank entries. Sequence
      manipulation tools, such as evolutionary tree generation, novel sequence
      assignment, and statistical analysis, are also provided. AVAILABILITY: The kinase
      sequence database is a web-based service accessible at http://kinase.ucsf.edu/ksd
      CONTACT: buzko@cmp.ucsf.edu; shokat@cmp.ucsf.edu/ksd

PMID- 12217925
TI  - PeCoP: automatic determination of persistently conserved positions in protein
      families.
AB  - PeCoP is a WWW-based service which accepts a protein sequence, and reports
      positions that are conserved in close and distant sequence family members. The
      collation of family members is performed using iterative PSI-BLAST runs.
      Examining positional conservation in close and distant family members enables a
      better selection of positions that may play a role in determining the protein's
      structure and function. AVAILABILITY: http://bioinformatics.org/pecop CONTACT:
      idoerg@burnham.org SUPPLEMENTARY INFORMATION:
      http://bioinformatics.org/pecop/about_pecop

PMID- 12217926
TI  - Applications of Tree-Maps to hierarchical biological data.
AB  - A brief overview of Tree-Maps provides the basis for understanding two new
      implementations of Tree-Map methods. TreeMapClusterView provides a new way to
      view microarray gene expression data, and GenePlacer provides a view of gene
      ontology annotation data. We also discuss the benefits of Tree-Maps to visualize
      complex hierarchies in functional genomics. AVAILABILITY: Java class files are
      freely available at http://mendel.mc.duke.edu/bioinformatics/ CONTACT:
      mccon012@mc.duke.edu SUPPLEMENTARY INFORMATION: For more information on
      TreeMapClusterView (see
      http://mendel.mc.duke.edu/bioinformatics/software/boxclusterview/), and
      http://mendel.mc.duke.edu/bioinformatics/software/geneplacer/).

PMID- 12217927
TI  - An ontology driven architecture for derived representations of macromolecular
      structure.
AB  - An object metamodel based on a standard scientific ontology has been developed
      and used to generate a CORBA interface, an SQL schema and an XML representation
      for macromolecular structure (MMS) data. In addition to the interface and schema
      definitions, the metamodel was also used to generate the core elements of a CORBA
      reference server and a JDBC database loader. The Java source code which
      implements this metamodel, the CORBA server, database loader and XML converter
      along with detailed documentation and code examples are available as part of the
      OpenMMS toolkit. AVAILABILITY: http://openmms.sdsc.edu CONTACT: dsg@sdsc.edu

PMID- 12217928
TI  - Cardioprotective effects of light-moderate consumption of alcohol: a review of
      putative mechanisms.
AB  - There is abundant epidemiological and clinical evidence showing that light
      moderate drinking is associated with a reduced risk of coronary heart disease
      (CHD), total and ischaemic stroke and total mortality in middle-aged and elderly
      men and women. The epidemiological evidence suggests a J- or U-shaped
      relationship between alcohol and CHD. However, the apparent benefits of moderate
      drinking on CHD mortality are offset at higher drinking levels by increasing risk
      of death from other types of heart diseases (cardiomyopathy, arrhythmia etc.),
      neurological disorders, cancer, liver cirrhosis, and traffic accidents. The
      plausible mechanisms for the putative cardioprotective effects include increased
      levels of high-density lipoprotein cholesterol, decreased levels of low-density
      lipoprotein cholesterol, prevention of clot formation, reduction in platelet
      aggregation, and lowering of plasma apolipoprotein(a) concentration. Thus,
      alcohol reduces the risk of coronary vascular diseases both by inhibiting the
      formation of atheroma and decreasing the rate of blood coagulation.

PMID- 12217929
TI  - A nice try that fails: the Swedish Council on Technology Assessment in Health
      Care (SBU) evaluation of the effect of treatment of alcohol and drug problems:
      the epidemiologist's view.
AB  - BACKGROUND AND AIMS: The Swedish Council on Technology Assessment in Health Care
      (SBU) has recently published a large, >800-page systematic review. It reviews
      brief interventions to reduce alcohol intake, long-term prognosis of substance
      dependence, obstetric questions and economic aspects of addiction treatments. The
      main part aims to evaluate treatments on alcohol and other addictive substances
      by meta-analytical techniques. RESULTS AND CONCLUSIONS: The report summarizes 641
      individual studies. Unfortunately, several methods are weak, some inadequately
      documented, and many conclusions rest on shaky grounds.

PMID- 12217930
TI  - The Swedish State Health Technology Board (SBU) report on treatment of alcohol
      and drug misuse: an economist's view.
AB  - The Swedish State Health Technology Board (SBU) has published a Report on the
      treatment of alcohol and drug misuse (SBU, 2001). This article is a brief
      Commentary on the economic issues raised in Chapter 9 of the Report, in
      particular, the question of 'how cost-effective are the different treatment
      alternatives?' An outline is given of how the authors approached the economic
      work, with particular reference to a standard checklist approach to judging the
      quality of published economic appraisals. A paucity of such appraisals was
      retrieved and detailed review of just 16 papers was undertaken. The authors are
      critical of the lack of quality of economic work in the substance misuse area and
      their main points are summarized here. The main conclusion drawn is that no
      economic judgements can be made about alternative treatment approaches, and more
      study and research are needed in this area. Chapter 9 is, on balance, a good
      attempt at a critical review of the economic appraisal literature. Unfortunately
      the main Report provides a series of summary judgements on the effectiveness or
      otherwise of alternative treatments, which, while recognizing the need for
      further cost-effectiveness work, essentially ignores the conclusion drawn in the
      economics chapter. This is likely to do a disservice to the cause of appropriate
      resource allocation in the substance misuse area.

PMID- 12217931
TI  - Intermittent ethanol exposure increases the number of cerebellar microglia.
AB  - AIMS: The number of cerebellar microglia after 5(1)/2 months of continuous or
      intermittent ethanol exposure was studied using the optical dissector method.
      METHODS: Male Wistar rats were divided into three groups: an intermittently
      ethanol-exposed group, a continuously ethanol-exposed group and a control group
      (n = 6 in each group). The intermittently treated rats had two ethanol-withdrawal
      periods per week throughout the experiment. The number of microglia was measured
      in the anterior (folium II) and the posterior (folium X) cerebellar vermis.
      Tomato (Lycopersicon esculentum) lectin was used to stain the cerebellar
      microglia. RESULTS: The volumes of folia II and X were similar in all the groups.
      The number of microglia increased in the molecular layer of folium II in the
      intermittently ethanol-exposed group compared with the continuously exposed and
      control groups. In the granular layer, there were no differences between the
      groups in the number of microglia. CONCLUSIONS: The results suggest that the
      number of cerebellar microglia increases in the anterior vermis before any
      ethanol-induced cerebellar atrophy is discernible. Repeated ethanol withdrawals
      seem to be more essential in inducing microgliosis than ethanol intoxication per
      se.

PMID- 12217932
TI  - Conditioned taste aversion and the Myers' high-ethanol-preferring rat.
AB  - AIMS: Male and female Myers' high-ethanol-preferring (mHEP) rats were compared to
      outbred controls in a taste aversion paradigm. METHODS: Alcohol-naive rats were
      adapted to a 2-h access to water. Each rat was given either 0.05% saccharin (w/v)
      or 7% ethanol (v/v) as a novel solution for 1 h, after which either 0.5 M LiCl,
      as the aversive stimulus, or NaCl, as the control, was injected
      intraperitoneally. Each rat was tested 48 h later by presentation of the same
      solution. RESULTS: After LiCl injections, saccharin consumption declined 21.6% in
      female Sprague-Dawley, 9.5% in female mHEP, 33.3% in male Wistar, and 38.3% in
      male mHEP rats. Ethanol consumption in these groups declined by 88.5, 30, 45 and
      52%, respectively. These mHEP rats were then screened for 24-h alcohol
      consumption on a 10-day 3-30% ethanol vs water 'step-up' procedure. During the
      step-up procedure, only the male mHEP rats trained with ethanol for taste
      aversion drank less ethanol at the 3-5% concentrations than did rats trained with
      saccharin. The female mHEP rats did not learn an aversion to either saccharin or
      ethanol. CONCLUSIONS: The female mHEP rat consumes copious amounts of ethanol,
      but the basis for this consumption may be different from that of the male mHEP
      rat.

PMID- 12217934
TI  - Sucrose self-administration predicts only initial phase of ethanol-reinforced
      behaviour in Wistar rats.
AB  - AIMS: To characterize the relationship between the sucrose- and ethanol
      reinforced behaviour in Wistar rats. METHODS: Subjects (n = 31) were trained to
      lever press for 8% (v/v) ethanol in an operant procedure where increasing
      concentrations of ethanol were introduced in the presence of 8% (w/v) sucrose.
      The sucrose concentration was subsequently decreased from 8 to 0%. Subjects were
      allowed to stabilize their intake of 8% ethanol over the next 20 days. RESULTS:
      Self-administration of 8% sucrose (ml/kg) significantly correlated with ethanol
      consumption (g/kg) on days 1-5 of the 8% ethanol self-administration period. This
      relationship completely disappeared during the subsequent weeks of ethanol self
      administration (days 6-20). CONCLUSIONS: The results of the present study,
      combined with our previous findings, may indicate that self-administration of
      sucrose predicts only the initial phase of ethanol-taking behaviour in Wistar
      rats.

PMID- 12217933
TI  - Effects of acetaldehyde on c-fos mRNA induction in the paraventricular nucleus
      following ethanol administration.
AB  - AIMS: The effect of acetaldehyde on c-fos mRNA expression in the paraventricular
      nucleus (PVN) of the rat was examined using in situ hybridization histochemistry.
      METHODS: Increases in acetaldehyde concentrations were induced using cyanamide (a
      potent inhibitor of aldehyde dehydrogenase), in the presence of two different
      doses of ethanol. Concentrations of blood ethanol and acetaldehyde were
      determined by head space gas chromatography. RESULTS: Neither cyanamide alone nor
      the low dose of ethanol (1 g/kg) alone increased c-fos expression in the PVN.
      However, the combination of cyanamide and low dose ethanol resulted in a
      significant and maximal increase in c-fos mRNA in the PVN. High dose ethanol (3
      g/kg) resulted in a significant increase in c-fos mRNA. This stimulation also
      appeared maximal as there was no further increase in c-fos expression in the
      presence of cyanamide. CONCLUSIONS: These data suggest that acetaldehyde
      accumulation in blood has an important stimulatory effect on c-fos expression in
      the PVN at low ethanol concentrations. Furthermore, this stimulation of c-fos
      mRNA appears to be an either/or response: not activated in response to low dose
      ethanol, but maximally to high dose ethanol. These data also provide further
      evidence for a dissociation between the activation of c-fos and corticotrophin
      releasing factor (CRF) mRNA in the PVN, as we have previously demonstrated that
      this dose of cyanamide alone is sufficient to evoke a sustained increase in
      plasma corticosterone and an increase in CRF mRNA.

PMID- 12217935
TI  - Changes in P300 latency during the early withdrawal period in chronic alcohol
      dependent patients: two case reports.
AB  - AIMS: The present study focused on changes in P300 of the event-related potential
      (ERP) in two patients with alcohol dependence recorded throughout their alcohol
      withdrawal period. RESULTS: As a result of this investigation, the peak latency
      of P300 in each patient was significantly shorter 2 or 3 days after abstinence
      from alcohol, when marked neurological manifestations appeared, compared to that
      of the control obtained from 8 to 10 days after cessation of drinking.
      CONCLUSIONS: It seems reasonable to conclude that the shortening of P300 latency
      reflects the enhancement of brain activity during the early withdrawal period and
      that an investigation of changes in P300 would be helpful to clarify the nature
      of neural activity in the brain associated with alcohol withdrawal.

PMID- 12217936
TI  - A comparison of alcohol screening instruments among under-aged drinkers treated
      in emergency departments.
AB  - AIMS: Few studies have examined the adequacy of adult-validated alcohol screening
      measures when used with adolescents and young adults. A total of 103 subjects (55
      males, 48 females) participated in a study of alcohol use among under-aged
      drinkers conducted in two emergency departments. METHODS: Participants completed
      three brief screening instruments for problematic alcohol use: the Alcohol Use
      Disorders Identification Test (AUDIT); a modified version of the TWEAK; and the
      CAGE. RESULTS AND CONCLUSIONS: Missing data on the TWEAK, lower internal
      consistency for the TWEAK and CAGE, and the better ability of the AUDIT to
      differentiate problem drinkers from non-problem drinkers, suggest that the AUDIT
      performs best in screening for problematic alcohol use among under-aged drinkers
      treated in emergency departments.

PMID- 12217937
TI  - Harmful drinking in military veterans with post-traumatic stress disorder:
      association with the D2 dopamine receptor A1 allele.
AB  - AIMS: The frequency of the Taq I A alleles (A1 and A2) of the D2 dopamine
      receptor (DRD2) gene was examined in Caucasian post-traumatic stress disorder
      (PTSD) patients and controls. RESULTS: In 91 PTSD patients, the frequency of the
      A1 allele was higher (P = 6.12 x 10(-3)) than in the 51 controls. In the 38 PTSD
      harmful drinkers (>or=60 g alcohol/day), A1 allelic frequency was higher (P =
      3.91 x 10(-2)) than in the 53 non-harmful drinkers (<60 g alcohol/day), the
      former being also higher (P = 3.76 x 10(-4)) than in controls. However, there was
      no difference between non-harmful drinkers and controls. Based on DRD2 allelic
      association, the 35 PTSD patients with the A1(+) (A1A1, A1A2) allele consumed
      more than twice the daily amount of alcohol than the 56 patients with the A1(-)
      (A2A2) allele (P = 1.94 x 10(-3)). When the hourly rate of alcohol consumed was
      compared, A1(+) allelic patients consumed twice the rate of the A1(-) allelic
      patients (P < 10(-7)). CONCLUSION: The DRD2 A1 allele was associated with PTSD.
      However, this association was found only in the harmful drinkers. PTSD patients
      with the A1(+) allele consumed more alcohol than patients with the A1(-) allele.
      The importance of determining alcohol consumption in DRD2 association studies
      with PTSD is suggested.

PMID- 12217938
TI  - High prevalence, persistent hazardous drinking among New Zealand tertiary
      students.
AB  - AIMS: To determine the prevalence of hazardous drinking and alcohol-related
      negative consequences in New Zealand tertiary students, and to identify
      predictors of hazardous drinking across a 6-month period. METHODS: A total of
      1480 tertiary students living in halls of residence was surveyed at the start of
      the academic year, and a subsample of 967 students was followed up 6 months
      later. Questionnaire items included quantity and frequency of drinking, alcohol
      related problems, use of other substances, and the Alcohol Use Disorders
      Identification Test (AUDIT). Drinking at follow-up was modelled using demographic
      characteristics, mental well-being, other substance use, alcohol-related
      problems, and hall drinking norms, measured at baseline. RESULTS: Among drinkers,
      mean (+/- SD) weekly consumption was 243 +/- 241 and 135 +/- 157 g of ethanol for
      males and females respectively. The majority of male (60.0%) and female (58.2%)
      drinkers typically consumed more than national safe drinking guidelines. Mean (+/
      SD) AUDIT scores were 10.9 +/- 7.6 for males and 7.6 +/- 5.9 for females. After
      controlling for AUDIT scores at baseline, increased AUDIT scores at follow-up
      were higher with lower age, Maori ethnicity, smoking, cannabis use, high levels
      of alcohol-related negative consequences, and higher levels of drinking in the
      student's hall of residence. CONCLUSIONS: Hazardous drinking is widespread and
      persistent among students living in the halls of residence. There is a need for
      university alcohol policies and intervention approaches among New Zealand
      tertiary students.

PMID- 12217939
TI  - Interpretation of items in the AUDIT questionnaire.
AB  - AIMS: To test for the possibility that tertiary students misinterpret certain
      items on the Alcohol Use Disorders Identification Test (AUDIT). METHODS:
      Responses to alternative question wordings were compared with responses to
      standard items. RESULTS: Alterations to items 5 and 9, so that consequences of
      drinking epitomized in these items were more specifically defined, resulted in
      markedly different response distributions to the item, but the total AUDIT score
      was not changed. CONCLUSIONS: Caution is necessary before using individual AUDIT
      items as measures of consequences in population surveys, and the possibility of
      false positives in total scores should be borne in mind.

PMID- 12217940
TI  - Alcohol and/or other drug use among adult non-occupant motor vehicle crash
      victims.
AB  - AIMS: To identify the frequency of current or lifetime history of alcohol and/or
      other drug (AOD) use among the full range (admitted and discharged) of injured
      bicyclists and pedestrians involved in motor vehicle crashes. METHODS: In a
      prospective study of non-occupant motor vehicle crash (NOMVC) victims >or=18
      years over a 29-month period, blood was obtained for alcohol and drug testing.
      Current alcohol abuse/alcohol dependence (AA/AD) or drug abuse/drug dependence
      (DA/DD) was based on the Diagnostic Interview Survey. RESULTS: In all, there were
      108 NOMVC victims. Eleven per cent were alcohol (+), 7% drug (+), and 3% both.
      Sixteen per cent were AA/AD (+), 2.7% DA/DD (+), and 1.4% both. CONCLUSIONS: A
      substantial portion of patients with NOMVC injuries tested AOD (+) and had a
      current or lifetime substance abuse (AA/AD; DA/DD) diagnosis.

PMID- 12217941
TI  - Hypouricaemia as a marker of a generalized proximal tubular damage in alcoholic
      patients.
AB  - AIMS AND METHODS: Hypouricaemia is not frequently encountered in alcoholic
      patients. Described herein is the case of a 69-year-old alcoholic patient.
      RESULTS: The patient presented with severe hypouricaemia (serum uric acid 95.2
      micro mol/l) due to renal urate wasting associated with a cluster of other
      metabolic abnormalities in the context of a reversible generalized dysfunction of
      the proximal tubules that mimicked Fanconi syndrome. CONCLUSIONS: The underlying
      mechanisms of this rare presentation are discussed.

PMID- 12217943
TI  - A potential role for GABA(B) agonists in the treatment of psychostimulant
      addiction.
AB  - AIMS: Here we briefly review the preclinical and clinical evidence that gamma
      aminobutyric acid (GABA(B)) agonists may be useful in the treatment of cocaine
      addiction. An extensive series of studies in rats has demonstrated that baclofen
      and other GABA(B) agonists reduce cocaine self-administration in an apparently
      specific manner. METHODS: A number of schedules of reinforcement, including fixed
      ratio, progressive-ratio and discrete trials procedures, have been used to model
      various aspects of cocaine reinforcement and addiction. RESULTS: The results show
      that systemic pretreatment with baclofen can reduce cocaine intake at doses that
      do not affect responding for other positive reinforcers, such as food. Direct
      intracerebral injections of baclofen into the ventral tegmental area also produce
      a specific reduction in cocaine self-administration, suggesting that an
      inhibition of dopaminergic neurons may be responsible for the effect. Recent
      clinical evidence and case reports indicate some therapeutic value for baclofen
      in controlling cocaine intake and craving, although the evidence from controlled
      clinical trials has been less than convincing. Perhaps the most intriguing data
      come from human imaging studies, wherein cocaine addicts report increased cocaine
      craving and activation of orbital-frontal cortex, anterior cingulate and amygdala
      when shown videotapes of drug paraphernalia and other addicts taking cocaine. The
      craving is reduced and the limbic activation is eliminated in cocaine-dependent
      patients who had been taking baclofen (10-20 mg twice daily) for 7-10 days.
      CONCLUSIONS: Systematic clinical studies of GABA(B) agonists are needed to
      determine the extent to which these drugs might serve as tools to promote
      abstinence in cocaine users seeking treatment for their addiction. Several areas
      must still be addressed, including potential side-effects that may limit
      compliance and whether GABA(B) agonists interfere with other, non-drug-related
      behaviours.

PMID- 12217944
TI  - GABAergic mechanisms of opiate reinforcement .
AB  - The neurobiological mechanisms of opiate-induced reinforcement are still not
      completely understood. Over the past two decades, the vast majority of studies
      have focused on the role of the mesolimbic dopamine (DA) system. However, current
      studies strongly suggest that opiate actions on gamma-aminobutyric acid (GABA)
      ergic cells in both the ventral tegmental area (VTA) and the nucleus accumbens
      (NAcc) appear to play critical roles. In this review, we focus on the
      neurochemical substrates of opiate reinforcement and review the role of DA and
      non-DA substrates, including opioid, GABA, glutamate and serotonin on opiate
      reinforced behaviour and the activity of dopaminergic and GABAergic neurons in
      the VTA and the NAcc.

PMID- 12217945
TI  - Baclofen antagonizes intravenous self-administration of nicotine in mice and
      rats.
AB  - AIMS: Gamma-aminobutyric acid (GABA)-ergic transmission plays an important role
      in modulating reinforcing effects of different drugs of misuse. In particular,
      stimulation of GABA(B) receptors negatively influences self-administration of
      cocaine, heroin, nicotine, alcohol and gamma-hydroxybutyric acid. The effect and
      specificity of the GABA(B) agonist baclofen on nicotine misuse were studied on
      two animal models of self-administration. METHODS: The effects of RS baclofen and
      the two isomers R baclofen and S baclofen were studied on the acute nicotine self
      administration in drug-naive mice. The effect of RS baclofen was also studied in
      rats trained to chronically self-administer nicotine under a continuous
      reinforcement (FR1) schedule. RESULTS: RS baclofen antagonizes nicotine
      intravenous self-administration at doses of 1.25-2.5 mg/kg intraperitoneally
      (i.p.). Furthermore, this effect is sterospecific. R baclofen completely
      prevented nicotine self-administration at the dose of 0.625 mg/kg i.p., whereas S
      baclofen was inactive up to the dose of 2.5 mg/kg i.p. In rats trained to self
      administer nicotine, pretreatment with RS baclofen at the dose of 2.5 mg/kg i.p.
      significantly increased the rate of responding for nicotine. This effect was
      similar to the effect obtained when rats were pretreated with the nicotine
      central receptor antagonist mecamylamine (1 mg/kg i.p.). CONCLUSIONS: These data
      show that baclofen is able to antagonize nicotine-rewarding effects in mice and
      rats and suggest its potential clinical utility for the treatment of nicotine
      misuse.

PMID- 12217946
TI  - The GABA(B) receptor agonists baclofen and CGP 44532 prevent acquisition of
      alcohol drinking behaviour in alcohol-preferring rats.
AB  - AIMS: The present study investigated the effect of the gamma-aminobutyric acid
      (GABA)(B) receptor agonists, baclofen and CGP 44532, on the acquisition of
      alcohol drinking behaviour in selectively bred Sardinian alcohol-preferring (sP)
      rats. METHODS: Baclofen [0, 1 and 3 mg/kg, intraperitoneally (i.p.)] and CGP
      44532 (0, 0.1, 0.3 and 1 mg/kg, i.p.) were administered immediately before
      alcohol presentation to alcohol-naive sP rats. Alcohol was offered under the two
      bottle free-choice regimen with unlimited access for 24 h/day. Drug treatment was
      repeated once daily for 10 consecutive days. RESULTS: Baclofen and CGP 44532,
      dose-dependently and with comparable efficacy, suppressed alcohol intake;
      compensatory increases in water intake left total fluid intakes virtually
      unchanged. CONCLUSIONS: These results demonstrate that baclofen and CGP 44532
      prevent the acquisition of alcohol drinking behaviour in sP rats, and suggest the
      involvement of the GABA(B) receptor in the mechanisms underlying the disclosure
      and experience of the reinforcing properties of alcohol in this rat line.

PMID- 12217947
TI  - Baclofen efficacy in reducing alcohol craving and intake: a preliminary double
      blind randomized controlled study.
AB  - AIMS: The gamma-aminobutyric acid (GABA(B)) receptor agonist, baclofen, has
      recently been shown to reduce alcohol intake in alcohol-preferring rats and
      alcohol consumption and craving for alcohol in an open study in humans. The
      present study was aimed at providing a first evaluation of the efficacy of
      baclofen in inducing and maintaining abstinence and reducing craving for alcohol
      in alcohol-dependent patients in a double-blind placebo-controlled design.
      METHODS: A total of 39 alcohol-dependent patients were consecutively enrolled in
      the study. After 12-24 h of abstinence from alcohol, patients were randomly
      divided into two groups. Twenty patients were treated with baclofen and 19 with
      placebo. Drug and placebo were orally administered for 30 consecutive days.
      Baclofen was administered at the dose of 15 mg/day for the first 3 days and 30
      mg/day for the subsequent 27 days, divided into three daily doses. Patients were
      monitored as out-patients on a weekly basis. At each visit alcohol intake,
      abstinence from alcohol, alcohol craving and changes in affective disorders were
      evaluated. RESULTS: A higher percentage of subjects totally abstinent from
      alcohol and a higher number of cumulative abstinence days throughout the study
      period were found in the baclofen, compared to the placebo, group. A decrease in
      the obsessive and compulsive components of craving was found in the baclofen
      compared to the placebo group; likewise, alcohol intake was reduced in the
      baclofen group. A decrease in state anxiety was found in the baclofen compared to
      the placebo group. No significant difference was found between the two groups in
      terms of current depressive symptoms. Baclofen proved to be easily manageable and
      no patient discontinued treatment due to the presence of side-effects. No patient
      was affected by craving for the drug and/or drug abuse. CONCLUSIONS: Baclofen
      proved to be effective in inducing abstinence from alcohol and reducing alcohol
      craving and consumption in alcoholics. With the limits posed by the small number
      of subjects involved, the results of this preliminary double-blind study suggest
      that baclofen may represent a potentially useful drug in the treatment of alcohol
      dependent patients and thus merits further investigations.

PMID- 12217948
TI  - Validation in mesenchymal progenitor cells of a mutation-independent ex vivo
      approach to gene therapy for osteogenesis imperfecta.
AB  - Over 100 dominant-negative mutations within the COL1A1 gene have been identified
      in osteogenesis imperfecta (OI). In terms of human therapeutics, targeting each
      of these mutations independently is unlikely to be feasible. Here we show that
      the hammerhead ribozyme Rzpol1a1, targeting a common polymorphism within
      transcripts from the COL1A1 gene, downregulates COL1A1 transcript in human
      mesenchymal progenitor cells at a ribozyme to transcript ratio of only 1:1.
      Downregulation was confirmed at the protein level. Transducing stem cells with
      Rzpol1A1 ex vivo followed by autologous transplantation could provide a gene
      therapy for a large proportion of OI patients with gain-of-function mutations
      using a single therapeutic.

PMID- 12217949
TI  - Estimating the statistical significance of gene expression changes observed with
      oligonucleotide arrays.
AB  - We present a simple method to assign approximate P-values to gene expression
      changes detected with Affymetrix oligonucleotide arrays and software. The method
      pools data for groups of genes and a small number of like-to-like comparisons in
      order to estimate the significance of changes observed for single genes in
      comparisons of experimental interest. Statistical significance levels are based
      on the observed variability in the fractional majority of probe pairs that
      indicate increasing or decreasing differential expression in comparisons of
      technical replicates. From this reference distribution or error model, we compute
      the expected frequency for fractional majorities in comparisons for N > or = 2.
      These computed distributions are the source of P-value estimates for changes seen
      in the experimental comparisons. The method is intended to complement the
      Affymetrix software and to rationalize gene selection for experimental designs
      involving limited replication.

PMID- 12217950
TI  - Evaluating test statistics to select interesting genes in microarray experiments.
AB  - A randomization procedure to evaluate the significance level and the false
      discovery rate in complex microarray experiments is proposed. A related graph can
      be used to compare different test statistics that can be used to analyze the same
      experiment. This graph is closely related to receiver operator characteristic
      (ROC) curves. The proposed method is applied to a subset of the data from a cell
      line experiment related to Huntington's disease. A small simulation study
      compares the effectiveness of the proposed procedure with the significance
      analysis of microarrays (SAM) procedure.

PMID- 12217951
TI  - Identification of a presymptomatic molecular phenotype in Hdh CAG knock-in mice.
AB  - The hallmark striatal neurodegeneration of Huntington's disease (HD) is first
      triggered by a dominant property of the expanded glutamine tract in mutant
      huntingtin that increases in severity with glutamine size. Indeed 111-glutamine
      murine huntingtin leads to a dominant cascade of phenotypes in Hdh(Q111) mice,
      although these abnormalities are not manifest in Hdh(Q50) mice, with 50-glutamine
      mutant protein. Therefore, to identify phenotypes that might reflect events
      closer to the fundamental trigger mechanism, and that can be measured as a
      consequence of adult-onset HD mutant huntingtin, we have screened for altered
      expression of genes conserved in evolution, which are likely to encode essential
      proteins. Probes generated from Hdh(Q111) homozygote and wild-type striatal RNAs
      were hybridized to human gene segments on filter arrays, disclosing a mutant
      specific increase in hybridization to Rrs1, encoding a ribosomal protein.
      Subsequent, quantitative RT-PCR assays demonstrated increased Rrs1 mRNA from 3
      weeks of age in homozygous and heterozygous Hdh(Q111) striatum and increased Rrs1
      mRNA expression with a single copy's worth of 50-glutamine mutant huntingtin in
      Hdh(Q50) striatum. Moreover, quantitative RT-PCR assays for the human homologue
      demonstrated elevated Rrs1 mRNA in HD compared with control postmortem brain.
      These findings, therefore, support a chronic impact of mutant huntingtin on an
      essential ribosomal regulatory gene to be investigated for its role very early in
      HD pathogenesis.

PMID- 12217952
TI  - PRODH mutations and hyperprolinemia in a subset of schizophrenic patients.
AB  - The increased prevalence of schizophrenia among patients with the 22q11
      interstitial deletion associated with DiGeorge syndrome has suggested the
      existence of a susceptibility gene for schizophrenia within the DiGeorge syndrome
      chromosomal region (DGCR) on 22q11. Screening for genomic rearrangements of 23
      genes within or at the boundaries of the DGCR in 63 unrelated schizophrenic
      patients and 68 unaffected controls, using quantitative multiplex PCR of short
      fluorescent fragments (QMPSF), led us to identify, in a family including two
      schizophrenic subjects, a heterozygous deletion of the entire PRODH gene encoding
      proline dehydrogenase. This deletion was associated with hyperprolinemia in the
      schizophrenic patients. In addition, two heterozygous PRODH missense mutations
      (L441P and L289M), detected in 3 of 63 schizophrenic patients but in none among
      68 controls, were also associated with increased plasma proline levels.
      Segregation analysis within the two families harboring respectively the PRODH
      deletion and the L441P mutation showed that the presence of a second PRODH
      nucleotide variation resulted in higher levels of prolinemia. In two unrelated
      patients suffering from severe type I hyperprolinemia with neurological
      manifestations, we identified a homozygous L441P PRODH mutation, associated with
      a heterozygous R453C substitution in one patient. These observations demonstrate
      that type I hyperprolinemia is present in a subset of schizophrenic patients, and
      suggest that the genetic determinism of type I hyperprolinemia is complex, the
      severity of hyperprolinemia depending on the nature and number of hits affecting
      the PRODH locus.

PMID- 12217953
TI  - Multiple susceptibility loci for multiple sclerosis.
AB  - Multiple sclerosis (MS) is a common and frequently disabling autoimmune disorder
      mediated by autoaggressive T cells and autoantibodies that target central nervous
      system myelin. While numerous studies have demonstrated a strong genetic
      component to MS, it has been difficult to identify the specific genes involved.
      Several genomic screens have been undertaken to locate such genes, but have not
      provided consistent gene localization, except for the MHC on chromosome 6p21 and
      a locus on chromosome 19q13. To determine which of the original genomic locations
      presented in the US genome screen could be replicated, a more detailed analysis
      of additional families was performed. The results, derived from a population of
      266 affected individuals belonging to 98 multiplex families, continue to support
      linkage to chromosomes 6p21, 6q27, and 19q13 with LOD scores>3.0, and suggest
      that regions on chromosomes 12q23-24 and 16p13 may also harbor susceptibility
      loci for MS. Analysis taking into account the known HLA-DR2 association
      identified two additional potential linkage regions on chromosomes 7q21-22 and
      13q33-34. These regions can now be targeted for detailed study to identify the
      underlying MS susceptibility genes.

PMID- 12217954
TI  - Fine mapping of a multiple sclerosis locus to 2.5 Mb on chromosome 17q22-q24.
AB  - Genome-wide linkage analyses performed in a Finnish study sample have identified
      four potential predisposing loci for multiple sclerosis (MS). Here we made an
      effort to restrict the wide linkage region on chromosome 17 with a dense set of
      31 markers using multipoint linkage analyses and monitoring for shared marker
      alleles in MS chromosomes. We carried out the linkage analyses in 22 Finnish
      multiplex MS families originating from a regional subisolate that shows an
      exceptionally high prevalence of MS in order to minimize the genetic and
      environmental heterogeneity of the study sample. Thirty markers on the 23 cM
      initial interval gave positive pairwise LOD scores. We monitored for shared
      haplotypes among affected family members within a family, and identified an
      approximately 4 cM region flanked by the markers D17S1792 and ATA43A10 in 17 out
      of the 22 families (77.3%). The multipoint linkage analyses using Genehunter and
      SIMWALK 2.40 provided further evidence for the same 4 cM region, for example a
      maximal multipoint NPL score of 5.98 (P<0.0002). We observed nominal evidence for
      association to MS, with one marker flanking the shared region, and this
      association was replicated in the additional set of families. Using the combined
      power of linkage, association and shared haplotype analyses, we were thus able to
      restrict the MS locus on chromosome 17q from 23 cM to a 4 cM region covering a
      physical interval of approximately 2.5 Mb. Thus, this study describes the
      restriction of an MS locus outside the HLA region into a segment approachable by
      molecular tools.

PMID- 12217955
TI  - Nucleocytoplasmic transfer of the NF2 tumor suppressor protein merlin is
      regulated by exon 2 and a CRM1-dependent nuclear export signal in exon 15.
AB  - The neurofibromatosis 2 protein merlin is a classical tumor suppressor protein.
      Germline mutations predispose to the development of schwannomas, meningiomas and
      ependymomas. Merlin has been implicated in cellular migration and adhesion. This
      function is reflected in its subcellular localization at the plasma membrane and
      known interacting partners. Merlin has been regarded as an exception in not
      exerting a functional role within the nucleus as other tumor suppressors do.
      Here, we show that detection of wild-type protein in the nucleus is a rare event.
      However, splicing out of exon 2 leads to unrestricted entry into the nucleus.
      Skipping of adjacent exon 3 has no comparable effect ruling out an unspecific
      effect due to misfolding of the 4.1/JEF domain. Exon 2 functions as a cytoplasmic
      retention factor as it is able to confer sole cytoplasmic localization to a GFP
      fusion protein. Nuclear entry of merlin is thus regulated by alternative splicing
      within the 4.1/JEF domain and analogous to band 4.1 protein. Merlin's ability to
      enter the nucleus is complemented by a full nuclear-cytoplasmic shuttle protein
      with a functional Rev-type nuclear export sequence (NES) within exon 15 that
      facilitates export via the CRM1/exportin pathway. Deletion of this NES or
      treatment with the CRM1-specific inhibitor leptomycin B leads to overall nuclear
      accumulation of merlin isoforms missing exon 2. A cellular function different to
      the wild-type protein is implied for naturally occurring splice variants lacking
      exon 2. A putative effect of merlin as a transcriptional regulator and
      identification of nuclear binding partners remains to be elucidated.

PMID- 12217956
TI  - Modulation of polyglutamine-induced cell death by genes identified by expression
      profiling.
AB  - The majority of triplet-repeat diseases are caused by mutated genes with an
      extended polyglutamine tract, exemplified by Huntington's disease (HD). In order
      to model HD pathogenesis in a controlled system, we developed stable PC12 cell
      lines that express exon 1 fragments of the huntingtin gene with 23 or 74
      polyglutamines driven by an inducible doxycycline (dox)-sensitive promoter (HD
      23Q or HD-74Q). We aimed to identify early perturbations induced by the mutation
      by studying expression levels of 1824 genes at 0, 5, 10 and 18 hours after
      induction, using adaptor-tagged competitive PCR (ATAC-PCR). At these time points,
      the cells show no appreciable death or mitochondrial impairment and very low
      inclusion levels. A total of 126 genes, including 69 known genes, exhibited
      statistically significant alterations in the HD-74Q cell lines but no changes in
      the HD-23Q lines. We tested 11 of these genes for their abilities to modulate
      polyglutamine-induced cell death in transiently transfected cell models. Five
      genes [glucose transporter 1 (Glut1), phosphofructokinase muscle isozyme (Pfkm),
      prostate glutathione-S -transferase 2 (Gstm2), RNA-binding motif protein 3 (Rbm3)
      and KRAB-A interacting protein 1 (Krip-1)] significantly suppressed cell death in
      both neuronal precursor and non-neuronal cell lines, suggesting that these
      transcriptional changes were relevant to polyglutamine pathology. The efficient
      recovery of functionally relevant genes supports the utility of gene expression
      profiling for discovering pathways related to pathogenesis, and the importance of
      analyzing molecular events in the early stages of disease.

PMID- 12217957
TI  - Linkage disequilibrium between polymorphisms in the human TNFRSF1B gene and their
      association with bone mass in perimenopausal women.
AB  - Osteoporosis is a multifactorial disease with a strong genetic component
      characterized by reduced bone density and increased fracture risk. A candidate
      locus for regulation of hip bone mineral density (BMD) has been identified on
      chromosome 1p36 by linkage analysis. One of the positional and functional
      candidate genes located within this region is the tumour necrosis factor receptor
      superfamily member 1B (TNFRSF1B). In order to investigate whether allelic
      variation in TNFRSF1B contributes to regulation of bone mass, we studied several
      polymorphisms of this gene in a population based cohort study of 1240
      perimenopausal women from the UK. We studied a T676G change in exon 6 (196: Met
      Arg) and three SNPs (G593A, T598G, and T620C) in the 3'UTR of the gene. The 3'UTR
      SNPs were in strong linkage disequilibrium (LD) with each other (P<0.00001), and
      the exon 6 SNP was in LD with G593A and T598G (P<0.00001). We found no
      association between T676G alleles and BMD at the spine or hip. However, haplotype
      analysis showed that subjects homozygous for the A593-T598-C620 haplotype (n=85)
      had femoral neck BMD values 5.7% lower than those who did not carry the haplotype
      (n=1155; P<0.00008) and this remained significant after correcting for
      confounding factors and multiple testing (P<0.0009). Regression analysis showed
      that the ATC haplotype accounted for 1.2% of the population variance in hip BMD
      and was the second strongest predictor after body weight. In summary, our work
      supports the view that allelic variation in the 3'UTR of TNFRSF1B gene
      contributes to the genetic regulation of bone mass, with effects that are
      specific for femoral neck BMD.

PMID- 12217958
TI  - Muscle-specific alternative splicing of myotubularin-related 1 gene is impaired
      in DM1 muscle cells.
AB  - The myotubularin-related 1 (MTMR1) gene belongs to a highly conserved family of
      eucaryotic phosphatases, with at least 11 members in humans. The founder member
      of this gene family, MTM1, is mutated in X-linked myotubular myopathy, a severe
      congenital disorder that affects skeletal muscle, and codes for myotubularin, a
      specific phosphatidylinositol 3-phosphate [PI(3)P] phosphatase. MTM1 and MTMR1
      are adjacent on the X chromosome, and the corresponding proteins share 59%
      sequence identity. In the present study, we investigated the putative role of
      MTMR1 in myogenesis by analysing its expression pattern in muscle cells during
      differentiation and in skeletal muscle throughout development. We have identified
      three novel coding exons in the MTMR1 intron 2 that are conserved between mouse
      and human, are alternatively spliced, and give rise to six mRNA isoforms. One of
      the transcripts is muscle-specific and is induced during myogenesis both in vitro
      and in vivo, and represents the major isoform in adult skeletal muscle. We show
      that the two main MTMR1 protein muscular isoforms, like myotubularin, efficiently
      dephosphorylate PI(3)P in vitro. We have also analysed whether MTMR1 alternative
      splicing is affected in skeletal muscle cells derived from patients with
      congenital myotonic dystrophy (cDM1), in which mRNA splicing disturbances of
      specific genes are thought to constitute an important pathogenic mechanism. We
      found a striking reduction in the level of the muscle-specific isoform and the
      appearance of an abnormal MTMR1 transcript in differentiated cDM1 muscle cells in
      culture and in skeletal muscle from cDM1 patients. Our results suggest that MTMR1
      plays a role in muscle formation and represents a novel target for abnormal mRNA
      splicing in myotonic dystrophy.

PMID- 12217959
TI  - Mutations of the GREAT gene cause cryptorchidism.
AB  - In humans, failure of testicular descent (cryptorchidism) is one of the most
      frequent congenital malformations, affecting 1-3% of newborn boys. The clinical
      consequences of this abnormality are infertility in adulthood and a significantly
      increased risk of testicular malignancy. Recently, we described a mouse transgene
      insertional mutation, crsp, causing high intraabdominal cryptorchidism in
      homozygous males. A candidate gene Great (G-protein-coupled receptor affecting
      testis descent), was identified within the transgene integration site. Great
      encodes a seven-transmembrane receptor with a close similarity to the
      glycoprotein hormone receptors. The Great gene is highly expressed in the
      gubernaculum, the ligament that controls testicular movement during development,
      and therefore may be responsible for mediating hormonal signals that affect
      testicular descent. Here we show that genetic targeting of the Great gene in mice
      causes infertile bilateral intraabdominal cryptorchidism. The mutant gubernaculae
      fail to differentiate, indicating that the Great gene controls their development.
      Mutation screening of the human GREAT gene was performed using DHPLC analysis of
      the genomic DNA from 60 cryptorchid patients. Nucleotide variations in GREAT cDNA
      were found in both the patient and the control populations. A unique missense
      mutation (T222P) in the ectodomain of the GREAT receptor was identified in one of
      the patients. This mutant receptor fails to respond to ligand stimulation,
      implicating the GREAT gene in the etiology in some cases of cryptorchidism in
      humans.

PMID- 12217960
TI  - Poly(ADP-ribose) polymerase 2 localizes to mammalian active centromeres and
      interacts with PARP-1, Cenpa, Cenpb and Bub3, but not Cenpc.
AB  - Poly(ADP-ribose) polymerase 2 (PARP-2) is a newly discovered member of the PARP
      family. We report the association of PARP-2 with mammalian centromeres in a cell
      cycle-dependent manner, accumulating at centromeres during prometaphase and
      metaphase, disassociating during anaphase, and disappearing from the centromeres
      by telophase. Analysis of a pseudodicentric chromosome and a human neocentromere
      indicates that PARP-2 binding occurs only at active centromeres in a sequence
      independent manner. Centromere binding peaks at the outer centromere region, and
      is significantly enhanced upon treatment with microtubule-inhibiting drugs. Co
      immunoprecipitation assay demonstrates interaction between PARP-2 and its
      functional homolog PARP-1, constitutive centromere proteins Cenpa and Cenpb, and
      spindle checkpoint protein Bub3, but not with a third constitutive centromere
      protein Cenpc. These results, together with our previous demonstration that PARP
      1 displays an identical binding pattern with Cenpa, Cenpb and Bub3, but not
      Cenpc, and that all three proteins undergo significant poly(ADP-ribosyl)ation
      upon gamma-irradiation of cells, point to possible diverse roles of PARP-2 and
      PARP-1 in modulating the structure and checkpoint functions of the mammalian
      centromere, in particular during radiation-induced DNA damage.

PMID- 12217961
TI  - ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lg.
AB  - In the endoplasmic reticulum (ER) of eukaryotes, N-linked glycans are first
      assembled on the lipid carrier dolichyl pyrophosphate. The GlcNAc(2)Man(9)Glc(3)
      oligosaccharide is transferred to selected asparagine residues of nascent
      polypeptides. Defects along the biosynthetic pathway of N-glycans are associated
      with severe multisystemic syndromes called congenital disorders of glycosylation.
      Here, we describe a deficiency in the ALG12 ER alpha1,6-mannosyltransferase
      resulting in a novel type of glycosylation disorder. The severe disease was
      identified in a child presenting with psychomotor retardation, hypotonia, growth
      retardation, dysmorphic features and anorexia. In the patient's fibroblasts, the
      biosynthetic intermediate GlcNAc(2)Man(7) oligosaccharide was detected both on
      the lipid carrier dolichyl pyrophosphate and on newly synthesized glycoproteins,
      thus pointing to a defect in the dolichyl pyrophosphate-GlcNAc(2)Man(7)-dependent
      ALG12 alpha1,6 mannosyltransferase. Analysis of the ALG12 cDNA in the CDG patient
      revealed compound heterozygosity for two point mutations that resulted in the
      amino acid substitutions T67M and R146Q, respectively. The impact of these
      mutations on ALG12 protein function was investigated in the Saccharomyces
      cerevisiae alg12 glycosylation mutant by showing that the yeast ALG12 gene
      bearing the homologous mutations T61M and R161Q and the human mutant ALG12 cDNA
      alleles failed to normalize the growth defect phenotype of the alg12 yeast model,
      whereas expression of the normal ALG12 cDNA complemented the yeast mutation. The
      ALG12 mannosyltransferase defect defines a new type of congenital disorder of
      glycosylation, designated CDG-Ig.

PMID- 12217962
TI  - Functional substitution for TAF(II)250 by a retroposed homolog that is expressed
      in human spermatogenesis.
AB  - TAF(II)250, the largest subunit of the general transcription factor TFIID, is
      expressed from the human X chromosome, at least in somatic cells. In male
      meiosis, however, the sex chromosomes are transcriptionally silenced, while the
      autosomes remain active. How then are protein-encoding genes transcribed during
      human male meiosis? Here we present a novel autosomal human gene, TAF1L, which is
      homologous to TAF(II)250 and is expressed specifically in the testis, apparently
      in germ cells. We hypothesize that during male meiosis, transcription of protein
      encoding genes relies upon TAF1L as a functional substitute for TAF(II)250. Like
      TAF(II)250, the human TAF1L protein can bind directly to TATA-binding protein, an
      essential component of TFIID. Most importantly, transfection with human TAF1L
      rescued the temperature-sensitive lethality of a hamster cell line mutant in
      TAF(II)250. TAF1L lacks introns and evidently arose by retroposition of a
      processed TAF(II)250 mRNA during primate evolution. The observation that TAF1L
      can functionally replace TAF(II)250 provides experimental support for the
      hypothesis that during male meiosis, autosomes provide cellular functions usually
      supplied by the X chromosome in somatic cells.

PMID- 12217963
TI  - Orientation and color columns in monkey visual cortex.
AB  - The literature on orientation and color columns in monkey visual cortex is
      reviewed. The orientation column model most consistent with existing data is one
      containing 'stripes' of alternating positive and negative orientation
      'singularities' (cytochrome oxidase blobs) which run along the centers of ocular
      dominance (OD) columns, with horizontal and vertical orientations alternating at
      interblob centers. Evidence is summarized suggesting that color is mapped
      continuously across the monkey's primary visual cortex, with the ends of the
      spectrum located at 'red' and 'blue' cytochrome oxidase blobs and extra-spectral
      purple located between adjacent red and blue blobs in the same OD column. In the
      orientation column model, the 'linear zones' of Obermayer and Blasdel have the
      appearance of the lines on a pumpkin. A pinwheel model of color columns,
      consistent with existing data, includes spectral and extra-spectral colors as
      spokes. Spectral iso-color lines run across iso-orientation lines in linear
      zones, while extra-spectral iso-color lines occupy the 'saddle points' of
      Obermayer and Blasdel. The color column model accounts for closure of the
      perceptual color circle, as proposed by Isaac Newton in 1704, but does not
      account for color opponency.

PMID- 12217964
TI  - Oculomotor effects of delta-9-tetrahydrocannabinol in humans: implications for
      the functional neuroanatomy of the brain cannabinoid system.
AB  - The significance of cannabinoid signaling for human cognition and motor control
      is still poorly understood. Here, we have investigated acute behavioral effects
      of oral delta-9-tetrahydrocannabinol (THC) with oculomotor paradigms in 12
      healthy human subjects. Compared to baseline testing: (i) THC increased latencies
      of reflexive visually guided saccades, while their accuracy was not affected;
      (ii) latencies of memory-guided saccades were unaffected, but THC modulated
      accuracy of these eye movements by increasing average gain and gain variability;
      (iii) frequency of anticipated memory-guided saccades and antisaccade errors was
      increased; (iv) the saccade amplitude/peak velocity relationships were not
      affected. These results show that THC acts on selected aspects of saccade
      control, namely spatial attention shifts, fine tuning of volitional saccades,
      spatial working memory and inhibition of inappropriate saccades. The pattern of
      effects suggests modulation of neuronal activity in substantia nigra pars
      reticulata and/or dorsolateral prefrontal cortex and sparing of the eye fields
      and the final motor pathway for saccades. Behaviorally, our findings reflect the
      distribution of CB-1 cannabinoid receptors in the human neocortex, basal ganglia
      and brainstem and provide evidence for participation of the cannabinoidergic
      system in high level control of saccades and associated cognitive functions.
      Saccadic eye movements may provide an objective measure of motor and cognitive
      effects of cannabinoids.

PMID- 12217965
TI  - Involvement of reelin and Cajal-Retzius cells in the developmental formation of
      vertical columnar structures in the cerebral cortex: evidence from the study of
      mouse presubicular cortex.
AB  - The mammalian cerebral cortex is organized into horizontal and vertical arrays of
      neurons and their fiber connections that form anatomically and physiologically
      distinct laminar and columnar compartments. However, the developmental
      mechanism(s) underlying this dichotomous pattern remains a mystery. We provide
      anatomical evidence suggesting that reelin, a diffusible protein produced and
      secreted by Cajal-Retzius cells, is involved in the developmental formation of
      the vertical cell structures in the mouse presubicular cortex, the unique site
      where the vertical columnar arrays of cortical plate neurons and their dendritic
      branches are clearly identified during the early postnatal period. Our results
      also suggest that reelin plays a role in the formation of these vertical
      structures by acting as an inhibitory or stop signal for cortical plate neurons
      and their dendritic extensions. In addition to having perturbed horizontal
      laminae, reeler mutant mice, lacking reelin, display disruption of these vertical
      structures. Based on the present findings, we hypothesize that reelin and Cajal
      Retzius cells regulate the developmental formation of not only horizontal
      laminations, but also vertical columnar structures in the cerebral cortex.

PMID- 12217966
TI  - Dynamics of cortico-subcortical cross-modal operations involved in audio-visual
      object detection in humans.
AB  - Very recently, a number of neuroimaging studies in humans have begun to
      investigate the question of how the brain integrates information from different
      sensory modalities to form unified percepts. Already, intermodal neural
      processing appears to depend on the modalities of inputs or the nature
      (speech/non-speech) of information to be combined. Yet, the variety of paradigms,
      stimuli and technics used make it difficult to understand the relationships
      between the factors operating at the perceptual level and the underlying
      physiological processes. In a previous experiment, we used event-related
      potentials to describe the spatio-temporal organization of audio-visual
      interactions during a bimodal object recognition task. Here we examined the
      network of cross-modal interactions involved in simple detection of the same
      objects. The objects were defined either by unimodal auditory or visual features
      alone, or by the combination of the two features. As expected, subjects detected
      bimodal stimuli more rapidly than either unimodal stimuli. Combined analysis of
      potentials, scalp current densities and dipole modeling revealed several
      interaction patterns within the first 200 micro s post-stimulus: in occipito
      parietal visual areas (45-85 micro s), in deep brain structures, possibly the
      superior colliculus (105-140 micro s), and in right temporo-frontal regions (170
      185 micro s). These interactions differed from those found during object
      identification in sensory-specific areas and possibly in the superior colliculus,
      indicating that the neural operations governing multisensory integration depend
      crucially on the nature of the perceptual processes involved.

PMID- 12217967
TI  - Changes of cortico-striatal effective connectivity during visuomotor learning.
AB  - It has been suggested that the cortico-striatal system might play a crucial role
      in learning behavioural plans of action. We have tested this hypothesis by
      studying the dynamics of functional coupling among the neural elements of cortico
      striatal circuitry. Human cerebral activity was measured with functional magnetic
      resonance imaging (fMRI) during the learning of an associative visuomotor task.
      Structural equation modelling of regional fMRI time-series was used to
      characterize learning-related changes in effective connectivity. We report that
      learning to associate visual instructions with motor responses significantly
      altered cortico-striatal functional couplings. Specific learning-related
      increases of effective connectivity were found in temporo-striatal and fronto
      striatal circuits. Connectivity among portions of the frontal cortex decreased as
      a function of learning. Temporo-frontal and parieto-frontal couplings were not
      altered during learning. We infer that novel visuomotor associations are
      established through the enhancement of specific cortico-striatal circuits, rather
      than through the alteration of direct temporo-frontal or parieto-frontal
      connectivity.

PMID- 12217968
TI  - Brain activity underlying encoding and retrieval of source memory.
AB  - Neural activity elicited during the encoding and retrieval of source information
      was investigated with event-related functional magnetic resonance imaging
      (efMRI). During encoding, 17 subjects performed a natural/artificial judgement on
      pictures of common objects which were presented randomly in one of the four
      quadrants of the display. At retrieval, old pictures were mixed with new ones and
      subjects judged whether each picture was new or old and, if old, indicated in
      which quadrant it was presented at encoding. During encoding, study items that
      were later recognized and assigned a correct source judgement elicited greater
      activity than recognized items given incorrect judgements in a variety of
      regions, including right lateral occipital and left prefrontal cortex. At
      retrieval, regions showing greater activity for recognized items given correct
      versus incorrect source judgements included the right hippocampal formation and
      the left prefrontal cortex. These findings indicate a role for these regions in
      the encoding and retrieval of episodic information beyond that required for
      simple item recognition.

PMID- 12217969
TI  - Activity-dependent modulation of synaptic transmission in the intact human motor
      cortex revealed with transcranial magnetic stimulation.
AB  - Activity-dependent modulation of cortical synaptic transmission is a fundamental
      mechanism involved in learning and memory storage. This modulation has been
      widely studied in in vitro brain slices and in vivo animal models. More recently,
      transcranial magnetic stimulation has allowed detection of activity-dependent
      excitability modulation occurring in the intact human primary motor cortex (MI)
      after execution of different kinds of motor tasks. Both increased and decreased
      MI excitability have been described after exercise. While increased MI
      excitability is generally considered direct expression of cortical synaptic
      plasticity, a controversy still exists as to whether decreased MI excitability
      reflects fatigue of central nervous system (CNS) structures or cortical neuronal
      reorganization taking place after exercise. Here, we extend previous findings in
      order to provide further support for the latter hypothesis. Abduction- adduction
      movements of the thumb performed for 1 min at 2 Hz frequency rate produce a 55%
      decrease in MI excitability of mean 30 min duration. Similar decrements in
      amplitude and duration of motor evoked potentials (MEPs) are not reached if the
      same task is performed once again during the maximal inhibition phase (10 min
      post-exercise) produced by a previous activation. Moreover, the same task
      performed at a lower (1 Hz) frequency rate produces no significant MEP changes
      but can transiently reverse activity-dependent depression obtained after previous
      2 Hz movements. Repeated execution of the same task (2 Hz), each being performed
      after recovery from a previously induced MEP depression, ceases to produce an MEP
      decrement, suggesting adaptation in MI excitability modulation. This adaptation
      is long lasting and task-specific, since a different motor task (1 min circular
      movement of the thumb) restores activity-dependent modulation. Overall, these
      findings suggest that the dynamic modulation of MEPs occurring after execution of
      different kinds of simple motor skills reflects some form of activity-dependent,
      plastic neuronal reorganization instead of CNS fatigue. Possible anatomo
      functional mechanisms involved in this activity-dependent modulation of MI
      excitability are discussed.

PMID- 12217970
TI  - Reciprocal alterations in pre- and postsynaptic inhibitory markers at chandelier
      cell inputs to pyramidal neurons in schizophrenia.
AB  - In the prefrontal cortex of subjects with schizophrenia, markers of the synthesis
      and re-uptake of GABA appear to be selectively altered in a subset of
      interneurons that includes chandelier cells. Determining the effect of these
      disturbances in presynaptic GABA markers on inhibitory signaling requires
      knowledge of the status of GABA(A) receptors at the postsynaptic targets of
      chandelier cells, the axon initial segments (AIS) of pyramidal neurons. Because
      the alpha(2) subunit of the GABA(A) receptor is preferentially localized at
      pyramidal neuron AIS, we quantified alpha(2) subunit immunoreactive AIS in tissue
      sections containing prefrontal cortex area 46 from 14 matched triads of subjects
      with schizophrenia, subjects with major depression and control subjects.
      Systematic, random sampling revealed that the mean number of alpha(2)-labeled AIS
      per mm(2) in subjects with schizophrenia was significantly (P = 0.007) increased
      by 113% compared to control subjects and non-significantly increased compared to
      subjects with major depression. Furthermore, within subjects with schizophrenia,
      the density of alpha(2)-labeled AIS was negatively correlated (r = -0.49, P =
      0.038) with the density of chandelier axon terminals immunoreactive for the GABA
      membrane transporter. These data suggest that GABA(A) receptors are up-regulated
      at pyramidal neuron AIS in response to deficient GABA neuro-transmission at
      chandelier axon terminals in schizophrenia. Thus, disturbances in inhibition at
      the chandelier neuron-pyramidal neuron synapse may be a critical component of
      prefrontal cortical dysfunction in schizophrenia.

PMID- 12217971
TI  - The pyramidal cell of the sensorimotor cortex of the macaque monkey: phenotypic
      variation.
AB  - Recent studies have revealed striking differences in pyramidal cell structure
      among cortical regions involved in the processing of different functional
      modalities. For example, cells involved in visual processing show systematic
      variation, increasing in morphological complexity with rostral progression from
      V1 through extrastriate areas. Differences have also been identified between
      pyramidal cells in somatosensory, motor and prefrontal cortex, but the extent to
      which the pyramidal cell phenotype may vary between these functionally related
      cortical regions remains unknown. In the present study we investigated the
      structure of layer III pyramidal cells in somatosensory and motor areas 3b, 4, 5,
      6 and 7b of the macaque monkey. Cells were intracellularly injected in fixed,
      flat-mounted cortical slices and analysed for morphometric parameters. The size
      of the basal dendritic arbours, the number of their branches and their spine
      density were found to vary systematically between areas. Namely, we found a trend
      for increasing complexity in dendritic arbour structure through areas 3b, 5 and
      7b. A similar trend occurred through areas 4 and 6. The differences in arbour
      structure may determine the number of inputs received by neurons and may thus be
      an important factor in determining function at the cellular and systems level.

PMID- 12217972
TI  - Intracellular characterization of suppressive responses in supragranular
      pyramidal neurons of cat primary auditory cortex in vivo.
AB  - Several suppressive processes shape the response properties of auditory neurons,
      namely lateral inhibition, non-monotonic rate level function and
      excitation/inhibition binaural interaction. By combining intracellular recording
      from and staining of layers 2 and 3 pyramidal neurons (PNs) in cat primary
      auditory cortex, we demonstrate the temporal aspects of depolarization and
      hyperpolarization underlying these suppressions using pure tone stimulation. Two
      populations can be distinguished by the occurrence of hyperpolarization following
      onset depolarization (O-DEP). In layer 2 PNs there is an absence of
      hyperpolarization following O-DEP, while in layer 3 PNs hyperpolarization follows
      O-DEP. The latency of O-DEP is shortest at the neuron's best frequency. The
      latency shortens as sound intensity increases. In non-monotonic PNs,
      hyperpolarization onset becomes shorter as sound intensity increases. This
      earlier onset of hyperpolarization shortens the duration of the preceding O-DEP,
      resulting in a decreased O-DEP amplitude. Diverse patterns in the temporal
      interaction of depolarization and hyperpolarization underlie the binaural
      suppression interaction. These results demonstrate that diverse suppressive
      responses result from differences in the temporal timing of excitation and
      inhibition. The present results also suggest the possibility of distinct
      connections between PNs responding in a similar manner.

PMID- 12217973
TI  - Homeostatic control of slow-wave and spindle frequency activity during human
      sleep: effect of differential sleep pressure and brain topography.
AB  - The impact of a 40 h sleep deprivation versus a 40 h multiple nap paradigm on
      topographic and temporal aspects of electroencephalographic (EEG) activity during
      the subsequent recovery sleep was investigated in 10 young volunteers in a
      controlled 'constant posture' protocol. The accumulation of sleep pressure with
      extended wakefulness could be significantly attenuated by intermittent naps. The
      differential sleep pressure conditions induced frequency- and topographic
      specific changes in the EEG slow wave range (0.5-5 Hz) and in the low (LSFA,
      12.25-13.25 Hz) and high spindle frequency activity range (HSFA, 13.75-16.5 Hz)
      during non-REM sleep. The observed increase of EEG slow-wave activity (SWA) after
      high sleep pressure was significantly more pronounced in the fronto-central (Fz,
      Cz) than in the parieto-occipital (Pz, Oz) derivations. Low sleep pressure after
      the nap paradigm decreased SWA with an occipital predominance. Spindle frequency
      activity showed a dissimilar homeostatic regulation: HSFA was significantly
      decreased after high sleep pressure and increased after low sleep pressure,
      exclusively in the centro-parietal brain region (Cz, Pz). LSFA was significantly
      enhanced after both manipulations. The data indicate that EEG activity, in
      particular frontal SWA and centro-parietal HSFA, are under a clear sleep-wake
      dependent homeostatic control and imply a reciprocal relationship in the
      homeostatic regulation of SWA and HSFA, which however shows different spatio
      temporal aspects.

PMID- 12217974
TI  - Glial and neuronal interactions during slow wave and paroxysmal activities in the
      neocortex.
AB  - Increasing evidence suggests that glial cells are endowed with the ability to
      externalize their activity to the extracellular space and to neurons. Since the
      same activity is influenced by the extracellular ionic concentrations and the
      neurotransmitters released by neurons, it is suggested that neurons and glia
      entertain a continuous exchange of information. This behavior might have a
      particular significance during cortical oscillations. In this study we analyzed
      the time and voltage relationships within simultaneously recorded neuron-glia
      pairs during normal states characterized by a slow (<1 Hz) sleep oscillation and
      during paroxysmal epileptic discharges. Our data show that cortical neurons and
      glia display coherent activities during the tested spontaneous oscillations. The
      onset of the depolarizing phase of the slow oscillation started in neurons and
      followed with a lag of 88 ms in nearby (1-2 mm) recorded glial cells. In
      contrast, the beginning of the hyperpolarizing phase was initiated in glial
      cells, and neurons followed after 79 ms, suggesting that glial activities are not
      exclusively the reflection of neuronal ones. Moreover, we tested neuronal
      excitability that resulted in phase opposition with the glial membrane potential,
      establishing that only the first 30% of the neuronal depolarization is efficient
      for synaptic volleys within cortical neuronal networks. Seizures were associated
      with shorter time lags at onset of depolarization (1.8 ms) and with delayed glial
      offset (102 ms). The voltage slope and amplitude at the onset of the paroxysmal
      depolarizations were higher than in the case of the slow oscillation. Together
      with the variation of neuronal excitability, these results suggest that the glial
      uptake of K(+) contributes to the abridged duration of the paroxysmal
      depolarization.

PMID- 12217975
TI  - Outcome after cardiac arrest outside hospital.

PMID- 12217976
TI  - Oral contraceptives, venous thromboembolism, and the courts.

PMID- 12217977
TI  - Managing acute appendicitis.

PMID- 12217978
TI  - NHS foundation trusts.

PMID- 12217979
TI  - Violence in society.

PMID- 12217980
TI  - AIDS debate fails to hit target at development summit.

PMID- 12217981
TI  - Medical council to investigate alleged research fraud.

PMID- 12217982
TI  - GP struck off after offering to "fix" kidney sale.

PMID- 12217983
TI  - Medical insurance crisis hits Australia's surgeons.

PMID- 12217984
TI  - Royal college issues new guidelines on gifts from drugs companies.

PMID- 12217985
TI  - Psychiatric Association to investigate abuse in China.

PMID- 12217986
TI  - Old smallpox vaccination may still protect.

PMID- 12217987
TI  - French emergency services reach crisis point.

PMID- 12217988
TI  - Family complains that "love drug'"will smear their name.

PMID- 12217989
TI  - Potential impact of public access defibrillators on survival after out of
      hospital cardiopulmonary arrest: retrospective cohort study.
AB  - OBJECTIVE: To estimate the potential impact of public access defibrillators on
      overall survival after out of hospital cardiac arrest. DESIGN: Retrospective
      cohort study using data from an electronic register. A statistical model was used
      to estimate the effect on survival of placing public access defibrillators at
      suitable or possibly suitable sites. SETTING: Scottish Ambulance Service.
      SUBJECTS: Records of all out of hospital cardiac arrests due to heart disease in
      Scotland in 1991-8. MAIN OUTCOME MEASURES: Observed and predicted survival to
      discharge from hospital. RESULTS: Of 15 189 arrests, 12 004 (79.0%) occurred in
      sites not suitable for the location of public access defibrillators, 453 (3.0%)
      in sites where they may be suitable, and 2732 (18.0%) in suitable sites.
      Defibrillation was given in 67.9% of arrests that occurred in possibly suitable
      sites for locating defibrillators and in 72.9% of arrests that occurred in
      suitable sites. Compared with an actual overall survival of 744 (5.0%), the
      predicted survival with public access defibrillators ranged from 942 (6.3%) to
      959 (6.5%), depending on the assumptions made regarding defibrillator coverage.
      CONCLUSIONS: The predicted increase in survival from targeted provision of public
      access defibrillators is less than the increase achievable through expansion of
      first responder defibrillation to non-ambulance personnel, such as police or
      firefighters, or of bystander cardiopulmonary resuscitation. Additional resources
      for wide scale coverage of public access defibrillators are probably not
      justified by the marginal improvement in survival.

PMID- 12217990
TI  - Angiotensin converting enzyme insertion or deletion polymorphism and coronary
      restenosis: meta-analysis of 16 studies.
AB  - OBJECTIVE: To assess the association between genotype at the insertion or
      deletion polymorphism of the angiotensin converting enzyme gene and risk of
      coronary restenosis after percutaneous coronary intervention. DESIGN: Meta
      analysis of studies before July 2001 that reported on these genotypes and risk of
      coronary restenosis after a percutaneous coronary intervention, with or without
      coronary stenting. RESULTS: 16 studies, involving 4631 patients undergoing a
      percutaneous coronary intervention, yielded 1683 patients with restenosis after a
      mean weighted follow up of 5.5 months. The combined odds ratio for restenosis in
      people with the DD genotype was 1.23 (99% confidence interval 1.03 to 1.46). When
      studies were grouped by size, however, the combined odds ratios for restenosis in
      people with the DD genotype were 1.94 (1.39 to 2.71) for studies with less than
      100 cases, 1.33 (0.92 to 1.93) for studies with 100-200 cases, and 0.92 (0.72 to
      1.18) for studies with more than 200 cases (trend P=0.02). Similarly, when
      studies were grouped by genotyping procedures, significantly larger odds ratios
      were found in the studies that did not conceal disease status from laboratory
      staff and in the studies that did not use a second polymerase chain reaction
      amplification to reduce genetic mistyping. CONCLUSION: Compared with other
      studies, larger and more rigorous studies show a weaker association between the
      angiotensin converting enzyme gene DD genotype and restenosis. Publication bias
      or detection biases can produce artefactual associations at least as large as
      those that might be expected for common polymorphisms in complex diseases,
      suggesting the need for larger and more rigorous genetic epidemiological
      investigations than are now customary.

PMID- 12217991
TI  - Coronary angioplasty and stenting.

PMID- 12217992
TI  - Socioeconomic and ethnic group differences in self reported health status and use
      of health services by children and young people in England: cross sectional
      study.
AB  - OBJECTIVES: To examine whether self reported health status and use of health
      services varies in children of different social class and ethnic group. DESIGN:
      Cross sectional study from the 1999 health survey for England. SUBJECTS: 6648
      children and young adults aged 2-20 years. SETTING: Private households in
      England. MAIN OUTCOME MEASURES: Proportion of children (or their parents)
      reporting episodes of acute illness in the preceding fortnight and prevalence of
      self reported longstanding illness. Proportion reporting specific illnesses.
      Proportion reporting that they had consulted a general practitioner in the
      preceding fortnight, attended hospital outpatient departments in the three
      preceding months, or been admitted to hospital in the preceding year. RESULTS:
      Large socioeconomic differences were observed between ethnic subgroups; a higher
      proportion of Afro-Caribbean, Indian, Pakistani, and Bangladeshi children
      belonged to lower social classes than the general population. The proportion of
      children and young adults reporting acute illnesses in the preceding two weeks
      was lower in Bangladeshi and Chinese subgroups (odds ratio 0.41, 95% confidence
      interval 0.27 to 0.61 and 0.46, 0.28 to 0.77, respectively) than in the general
      population. Longstanding illnesses was less common in Bangladeshi and Pakistani
      children (0.52, 0.40 to 0.67 and 0.57, 0.46 to 0.70) than in the general
      population. Irish and Afro-Caribbean children reported the highest prevalence of
      asthma (19.5% and 17.7%) and Bangladeshi children the lowest (8.2%). A higher
      proportion of Afro-Caribbean children reported major injuries than the general
      population (11.0% v 10.0%), and children from all Asian subgroups reported fewer
      major and minor injuries than the general population. Indian and Pakistani
      children were more likely to have consulted their general practitioner in the
      preceding fortnight than the general population (1.86, 1.35 to 2.57 and 1.51,
      1.13 to 2.01, respectively). Indian, Pakistani, Bangladeshi, and Chinese children
      were less likely to have attended outpatient departments in the preceding three
      months. No significant differences were found between ethnic groups in the
      admission of inpatients to hospitals. Acute and chronic illness were the best
      predictors of children's use of health services. Social classes did not differ in
      self reported prevalence of treated infections, major injuries, or minor
      injuries, and no socioeconomic differences were seen in the use of primary and
      secondary healthcare services. CONCLUSIONS: Children's use of health services
      reflected health status rather than ethnic group or socioeconomic status,
      implying that equity of access has been partly achieved, although reasons why
      children from ethnic minority groups are able to access primary care but receive
      less secondary care need to be investigated.

PMID- 12217993
TI  - Health promotion for adolescents in primary care: randomised controlled trial.
AB  - OBJECTIVES: To evaluate the effectiveness of inviting teenagers to general
      practice consultations to discuss health behaviour concerns and appropriate
      follow up care. DESIGN: Randomised controlled trial, with participants randomised
      to a consultation (intervention) or usual care (control). Questionnaires
      completed at baseline, 3 months, and 12 months. SETTING: Eight general practices
      in Hertfordshire, England. PARTICIPANTS: 1516 teenagers aged 14-15 years.
      INTERVENTION: Consultations with practice nurses to discuss health concerns and
      develop plans for healthier lifestyles. MAIN OUTCOME MEASURES: Mental and
      physical health, "stage of change" for health related behaviour, and use of
      health services. RESULTS: At baseline 970 teenagers completed questionnaires; 23%
      smoked, 35% had been drunk in the previous three months, 64% considered they ate
      unhealthily, 39% took little exercise, and 36% had possible depression. 41% (304)
      of teenagers invited attended for a consultation; over one third (112) were
      offered follow up care. More intervention group teenagers reported positive
      movement in stage of change for diet and exercise and in at least one of four
      behaviours (diet, exercise, smoking, drinking alcohol) at 3 months (41% v 31%,
      P<0.01), but this did not persist at 12 months. There was marginally more
      positive change in actual behaviour by intervention teenagers at 3 months (16% v
      12%, P=0.06). Recognition of possible depression resulted in improved mental
      health outcomes at 3 and 12 months. 97% of attenders said they would recommend
      the intervention to a friend. CONCLUSIONS: Change in behaviour was slight but
      encouraging, and the intervention was well received and relatively cheap.

PMID- 12217994
TI  - Survey of public information about ongoing clinical trials funded by industry:
      evaluation of completeness and accessibility.
AB  - OBJECTIVE: To evaluate the completeness and accessibility of public information
      about US clinical trials of drugs in development. DESIGN: Review of online
      registers of clinical trials. DATA SOURCES: Drugs in phase III trials were
      identified using three drug industry sources: PhRMA Survey, What's in the
      Pipeline, and the NDA Pipeline. Drug trials were then searched for on the
      following publicly accessible registers of clinical trials:, and registers
      associated with the 37 "Comprehensive Cancer Centers" designated by the National
      Cancer Institute. MAIN OUTCOME MEASURE: Extent of availability of public
      information on phase III trials of drugs in development for treating either
      prostate or colon cancer. RESULTS: Search of industry sources identified 12 drugs
      for prostate cancer and 20 for colon cancer undergoing phase III trials. The most
      comprehensive publicly available register, contained trial listings for only
      seven of the prostate cancer drugs and 10 of the colon cancer drugs. Trials of
      three prostate cancer and three colon cancer drugs were listed on only one
      register each. A substantial proportion of trials of prostate cancer drugs (3/12)
      and colon cancer drugs (8/20) were not associated with trial listings in any
      registers. CONCLUSIONS: Existing trials registers are unlikely to be meeting user
      needs since many ongoing drug trials are not listed. There is a clear need for a
      comprehensive clinical trials register encompassing all ongoing trials, including
      industry sponsored trials.

PMID- 12217995
TI  - Nitrous oxide anaesthesia in the presence of intraocular gas can cause
      irreversible blindness.

PMID- 12217996
TI  - Musculoskeletal pain.

PMID- 12217997
TI  - Mind the gap: the extent of the NHS nursing shortage.

PMID- 12217998
TI  - Mind the gap: the policy response to the NHS nursing shortage.

PMID- 12217999
TI  - More on the consultant contract. Framework doesn't consider anomaly of 100 000
      pounds sterling in lost earnings for some.

PMID- 12218000
TI  - Telephone use in primary care. Programme to shape demand has been started in
      several practices.

PMID- 12218001
TI  - Discussion of risk pervades doctor-patient communication.

PMID- 12218002
TI  - Stress and breast cancer. Basic error may have occurred.

PMID- 12218003
TI  - Genetic testing for familial Alzheimer's must be debated.

PMID- 12218004
TI  - Postmortem radiology is useful but no substitute for necropsy.

PMID- 12218005
TI  - Atomic force microscopy, a powerful tool in microbiology.

PMID- 12218006
TI  - Role of OxyR as a peroxide-sensing positive regulator in Streptomyces coelicolor
      A3(2).
AB  - Genes encoding a homolog of Escherichia coli OxyR (oxyR) and an alkyl
      hydroperoxide reductase system (ahpC and ahpD) have been isolated from
      Streptomyces coelicolor A3(2). The ahpC and ahpD genes constitute an operon
      transcribed divergently from the oxyR gene. Expression of both ahpCD and oxyR
      genes was maximal at early exponential phase and decreased rapidly as cells
      entered mid-exponential phase. Overproduction of OxyR in Streptomyces lividans
      conferred resistance against cumene hydroperoxide and H2O2. The oxyR mutant
      produced fewer ahpCD and oxyR transcripts than the wild type, suggesting that
      OxyR acts as a positive regulator for their expression. Both oxyR and ahpCD
      transcripts increased more than fivefold within 10 min of H2O2 treatment and
      decreased to the normal level in 50 min, with kinetics similar to those of the
      CatR-mediated induction of the catalase A gene (catA) by H2O2. The oxyR mutant
      failed to induce oxyR and ahpCD genes in response to H2O2, indicating that OxyR
      is the modulator for the H2O2-dependent induction of these genes. Purified OxyR
      protein bound specifically to the intergenic region between ahpC and oxyR,
      suggesting its direct role in regulating these genes. These results demonstrate
      that in S. coelicolor OxyR mediates H2O2 induction of its own gene and genes for
      alkyl hydroperoxide reductase system, but not the catalase gene (catA), unlike in
      Escherichia coli and Salmonella enterica serovar Typhimurium.

PMID- 12218007
TI  - Identification and localization of flagellins FlaA and FlaB3 within flagella of
      Methanococcus voltae.
AB  - Methanococcus voltae possesses four flagellin genes, two of which (flaB1 and
      flaB2) have previously been reported to encode major components of the flagellar
      filament. The remaining two flagellin genes, flaA and flaB3, are transcribed at
      lower levels, and the corresponding proteins remained undetected prior to this
      work. Electron microscopy examination of flagella isolated by detergent
      extraction of whole cells revealed a curved, hook-like region of varying length
      at the end of a long filament. Enrichment of the curved region of the flagella
      resulted in the identification of FlaB3 by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis and N-terminal sequencing, and the localization of this
      flagellin to the cell-proximal portion of the flagellum was confirmed through
      immunoblotting and immunoelectron microscopy with FlaB3-specific antibodies,
      indicating that FlaB3 likely composes the curved portion of the flagella. This
      could represent a unique case of a flagellin performing the role of the bacterial
      hook protein. FlaA-specific antibodies were used in immunoblotting to determine
      that FlaA is found throughout the flagellar filament. M. voltae cells were
      transformed with a modified flaA gene containing a hemagglutinin (HA) tag
      introduced into the variable region. Transformants that had replaced the wild
      type copy of the flaA gene with the HA-tagged version incorporated the HA-tagged
      version of FlaA into flagella which appeared normal by electron microscopy.

PMID- 12218008
TI  - Identification of GtgE, a novel virulence factor encoded on the Gifsy-2
      bacteriophage of Salmonella enterica serovar Typhimurium.
AB  - The Gifsy-2 temperate bacteriophage of Salmonella enterica serovar Typhimurium
      contributes significantly to the pathogenicity of strains that carry it as a
      prophage. Previous studies have shown that Gifsy-2 encodes SodCI, a periplasmic
      Cu/Zn superoxide dismutase, and at least one additional virulence factor. Gifsy-2
      encodes a Salmonella pathogenicity island 2 type III secreted effector protein.
      Sequence analysis of the Gifsy-2 genome also identifies several open reading
      frames with homology to those of known virulence genes. However, we found that
      null mutations in these genes did not individually have a significant effect on
      the ability of S. enterica serovar Typhimurium to establish a systemic infection
      in mice. Using deletion analysis, we have identified a gene, gtgE, which is
      necessary for the full virulence of S. enterica serovar Typhimurium Gifsy-2
      lysogens. Together, GtgE and SodCI account for the contribution of Gifsy-2 to S.
      enterica serovar Typhimurium virulence in the murine model.

PMID- 12218009
TI  - fleQ, the gene encoding the major flagellar regulator of Pseudomonas aeruginosa,
      is sigma70 dependent and is downregulated by Vfr, a homolog of Escherichia coli
      cyclic AMP receptor protein.
AB  - The flagellar transcriptional regulator FleQ appears to be the highest-level
      regulator in the hierarchical regulatory cascade of flagellar biogenesis in
      Pseudomonas aeruginosa. Except for the posttranslational downregulation of FleQ
      activity by FleN, an antiactivator, not much is known about the regulation of the
      fleQ gene or its gene product. Some FleQ homologs in other bacterial species
      either are positively regulated by another regulator (e.g., CtrA, the master
      regulator regulating FlbD in Caulobacter crescentus) or are expressed from a
      sigma70-dependent promoter (e.g., FlgR of Helicobacter pylori). In this study we
      demonstrated that Vfr, an Escherichia coli CRP homolog known to function as an
      activator for various genes, including lasR, regA, and toxA, in P. aeruginosa, is
      capable of repressing fleQ transcription by binding to its consensus sequence in
      the fleQ promoter. In a DNase I footprint assay, purified Vfr protected the
      sequence 5'-AATTGACTAATCGTTCACATTTG-3'. When this putative Vfr binding site in
      the fleQ promoter was mutated, Vfr was unable to bind the fleQ promoter fragment
      and did not repress fleQ transcription effectively. Primer extension analysis of
      the fleQ transcript revealed two transcriptional start sites, t1 and t2, that map
      within the Vfr binding site. A putative -10 region (TAAAAT) for the t2
      transcript, with a five-of-six match with the E. coli sigma70 binding consensus,
      overlaps with one end of the Vfr binding site. A 4-bp mutation and an 8-bp
      mutation in this -10 region markedly reduced the activity of the fleQ promoter.
      The same mutations led to the disappearance of the 203-nucleotide fleQ transcript
      in an in vitro transcription assay. Vfr probably represses fleQ transcription by
      binding to the Vfr binding site in the fleQ promoter and preventing the sigma
      factor from binding to the -10 region to initiate transcription.

PMID- 12218010
TI  - FleQ, the major flagellar gene regulator in Pseudomonas aeruginosa, binds to
      enhancer sites located either upstream or atypically downstream of the RpoN
      binding site.
AB  - In Pseudomonas aeruginosa, flagellar genes are regulated in a cascade headed by
      FleQ, an NtrC/NifA-type activator. FleQ and RpoN positively regulate expression
      of flhA, fliE, fliL, and fleSR genes, among others. Direct interaction of FleQ
      with flhA, fliE, fliL, and fleSR promoters was demonstrated by gel shift assay,
      along with experiments to conclusively determine the specificity of its binding.
      DNase I footprinting was performed to determine the FleQ binding sites on flhA,
      fliE, fliL, and fleSR promoters. No sequence conservation among these binding
      sites was observed. Primer extension analysis revealed the transcription start
      sites (TSSs) to be localized above the FleQ binding sites in flhA, fliE, and fliL
      promoters. Analysis of the above data revealed FleQ binding to be in the leader
      sequence of these promoters, whereas FleQ binding was 67 bp upstream of the TSS
      in the fleSR promoter. Mutagenesis of the FleQ binding site in the flhA promoter
      confirmed its functionality in vivo. Deletion of the flhA promoter upstream of
      the RNA polymerase binding site did not result in a significant loss of promoter
      activity. These results point to two modes of regulation by an NtrC-type
      regulator in the flagellar hierarchy in P. aeruginosa, the first being the
      typical model of activation from a distance via looping in the fleSR promoter and
      the second involving flhA, fliE, and fliL promoters, where FleQ binds in the
      downstream vicinity of the promoter and activates transcription without looping.

PMID- 12218011
TI  - Metabolism of dichloromethylcatechols as central intermediates in the degradation
      of dichlorotoluenes by Ralstonia sp. strain PS12.
AB  - Ralstonia sp. strain PS12 is able to use 2,4-, 2,5-, and 3,4-dichlorotoluene as
      growth substrates. Dichloromethylcatechols are central intermediates that are
      formed by TecA tetrachlorobenzene dioxygenase-mediated activation at two adjacent
      unsubstituted carbon atoms followed by TecB chlorobenzene dihydrodiol
      dehydrogenase-catalyzed rearomatization and then are channeled into a
      chlorocatechol ortho cleavage pathway involving a chlorocatechol 1,2-dioxygenase,
      chloromuconate cycloisomerase, and dienelactone hydrolase. However, completely
      different metabolic routes were observed for the three dichloromethylcatechols
      analyzed. Whereas 3,4-dichloro-6-methylcatechol is quantitatively transformed
      into one dienelactone (5-chloro-2-methyldienelactone) and thus is degraded via a
      linear pathway, 3,5-dichloro-2-methylmuconate formed from 4,6-dichloro-3
      methylcatechol is subject to both 1,4- and 3,6-cycloisomerization and thus is
      degraded via a branched metabolic route. 3,6-Dichloro-4-methylcatechol, on the
      first view, is transformed predominantly into one (2-chloro-3-methyl-trans-)
      dienelactone. In situ (1)H nuclear magnetic resonance analysis revealed the
      intermediate formation of 2,5-dichloro-4-methylmuconolactone, showing that both
      1,4- and 3,6-cycloisomerization occur with this muconate and indicating a
      degradation of the muconolactone via a reversible cycloisomerization reaction and
      the dienelactone-forming branch of the pathway. Diastereomeric mixtures of two
      dichloromethylmuconolactones were prepared chemically to proof such a hypothesis.
      Chloromuconate cycloisomerase transformed 3,5-dichloro-2-methylmuconolactone into
      a mixture of 2-chloro-5-methyl-cis- and 3-chloro-2-methyldienelactone, affording
      evidence for a metabolic route of 3,5-dichloro-2-methylmuconolactone via 3,5
      dichloro-2-methylmuconate into 2-chloro-5-methyl-cis-dienelactone. 2,5-Dichloro-3
      methylmuconolactone was transformed nearly exclusively into 2-chloro-3-methyl
      trans-dienelactone.

PMID- 12218012
TI  - Cold shock response in sporulating Bacillus subtilis and its effect on spore heat
      resistance.
AB  - Cold shock and ethanol and puromycin stress responses in sporulating Bacillus
      subtilis cells have been investigated. We show that a total of 13 proteins are
      strongly induced after a short cold shock treatment of sporulating cells. The
      cold shock pretreatment affected the heat resistance of the spores formed
      subsequently, with spores heat killed at 85 or 90 degrees C being more heat
      resistant than the control spores while they were more heat sensitive than
      controls that were heat treated at 95 or 100 degrees C. However, B. subtilis
      spores with mutations in the main cold shock proteins, CspB, -C, and -D, did not
      display decreased heat resistance compared to controls, indicating that these
      proteins are not directly responsible for the increased heat resistance of the
      spores. The disappearance of the stress proteins later in sporulation suggests
      that they cannot be involved in repairing heat damage during spore germination
      and outgrowth but must alter spore structure in a way which increases or
      decreases heat resistance. Since heat, ethanol, and puromycin stress produce
      similar proteins and similar changes in spore heat resistance while cold shock is
      different in both respects, these alterations appear to be very specific.

PMID- 12218013
TI  - A new modified ortho cleavage pathway of 3-chlorocatechol degradation by
      Rhodococcus opacus 1CP: genetic and biochemical evidence.
AB  - The 4-chloro- and 2,4-dichlorophenol-degrading strain Rhodococcus opacus 1CP has
      previously been shown to acquire, during prolonged adaptation, the ability to
      mineralize 2-chlorophenol. In addition, homogeneous chlorocatechol 1,2
      dioxygenase from 2-chlorophenol-grown biomass has shown relatively high activity
      towards 3-chlorocatechol. Based on sequences of the N terminus and tryptic
      peptides of this enzyme, degenerate PCR primers were now designed and used for
      cloning of the respective gene from genomic DNA of strain 1CP. A 9.5-kb fragment
      containing nine open reading frames was obtained on pROP1. Besides other genes, a
      gene cluster consisting of four chlorocatechol catabolic genes was identified. As
      judged by sequence similarity and correspondence of predicted N termini with
      those of purified enzymes, the open reading frames correspond to genes for a
      second chlorocatechol 1,2-dioxygenase (ClcA2), a second chloromuconate
      cycloisomerase (ClcB2), a second dienelactone hydrolase (ClcD2), and a
      muconolactone isomerase-related enzyme (ClcF). All enzymes of this new cluster
      are only distantly related to the known chlorocatechol enzymes and appear to
      represent new evolutionary lines of these activities. UV overlay spectra as well
      as high-pressure liquid chromatography analyses confirmed that 2-chloro-cis,cis
      muconate is transformed by ClcB2 to 5-chloromuconolactone, which during turnover
      by ClcF gives cis-dienelactone as the sole product. cis-Dienelactone was further
      hydrolyzed by ClcD2 to maleylacetate. ClcF, despite its sequence similarity to
      muconolactone isomerases, no longer showed muconolactone-isomerizing activity and
      thus represents an enzyme dedicated to its new function as a 5
      chloromuconolactone dehalogenase. Thus, during 3-chlorocatechol degradation by R.
      opacus 1CP, dechlorination is catalyzed by a muconolactone isomerase-related
      enzyme rather than by a specialized chloromuconate cycloisomerase.

PMID- 12218014
TI  - ilvIH operon expression in Escherichia coli requires Lrp binding to two distinct
      regions of DNA.
AB  - The leucine-responsive regulatory protein Lrp regulates the expression of a
      number of operons in Escherichia coli, including the ilvIH operon. Earlier in
      vitro experiments showed purified Lrp binding to two regions of DNA proximal to
      the ilvIH promoter, an upstream region (-260 to -190) and a downstream region (
      150 to -40). The effect of mutations in these regions on ilvIH promoter
      expression in vivo led to the proposal that activation of transcription required
      Lrp binding to downstream sites 3, 4, 5, and 6. Binding of Lrp to upstream sites
      1 and 2 seemed to enhance promoter expression but was not absolutely required (Q.
      Wang and J. M. Calvo, J. Mol. Biol. 229:306-318, 1993). Here we present data that
      require a reevaluation of the above conclusion. Constructs having either a
      deletion of DNA or a 100-bp substitution of DNA upstream of position -160 showed
      no ilvIH promoter activity in vivo. These results unambiguously establish that
      DNA at or upstream of position -160 is required for ilvIH promoter expression.
      Together with previous results, we conclude that Lrp bound at downstream sites is
      necessary but not sufficient for promoter activation. In addition, insertion of
      4, 6, 8, or 10 bp between the upstream and downstream regions also resulted in a
      very strong reduction of in vivo promoter expression, even though the binding of
      Lrp in vitro was not greatly affected by these mutations. Closer inspection
      showed that the affinity of Lrp for the upstream region of all of these
      constructs was about the same but that Lrp bound to the downstream region of the
      wild-type construct with a higher degree of cooperativity than in the case of the
      others. These mutations may have reduced promoter activity in vivo by eliminating
      a binding site for some transcription factor other than Lrp. Alternatively, the
      small-addition mutations may have affected the geometry of these complexes,
      preventing either an interaction between Lrps bound at upstream and downstream
      sites (which might be necessary for promoter expression) or preventing the
      positioning of Lrp bound at upstream sites for productive interaction with the
      promoter.

PMID- 12218015
TI  - Regulatory response of Methanococcus maripaludis to alanine, an intermediate
      nitrogen source.
AB  - In the methanogenic archaeon Methanococcus maripaludis, growth with ammonia
      results in conditions of nitrogen excess. Complete repression of nitrogen
      fixation (nif) gene transcription occurs, and glutamine synthetase (glnA) gene
      transcription falls to a basal constitutive level. In addition, ammonia
      completely switches off nitrogenase enzyme activity. In contrast, growth with
      dinitrogen as the sole nitrogen source results in nitrogen starvation, full
      expression of nif and glnA, and high activity of nitrogenase. Here we report that
      a third nitrogen source, alanine, results in an intermediate regulatory response.
      Growth with alanine resulted in intermediate transcription of nif and glnA, and
      addition of alanine to a nitrogen-fixing (diazotrophic) culture caused partial
      switch-off of nitrogenase. This uniformity of response occurred despite
      differences in regulatory mechanisms. Nitrogenase switch-off requires the
      nitrogen sensor homologs NifI(1) and NifI(2), while transcriptional regulation of
      nif and glnA relies on a different, unknown sensor mechanism. In addition,
      although nif and glnA transcription are governed by a common repressor, the
      numbers and arrangements of repressor binding sites differ. Thus, the nif
      promoter region contains two operators situated downstream of the transcription
      start site, while the glnA promoter region contains only one operator just
      upstream of two closely spaced transcription start sites. In a previous study of
      nif expression using ammonia, we were able to detect a role only for the first
      nif operator in repression. Here we show that nif repression by alanine requires
      the second operator as well. In contrast, in the case of glnA the single operator
      was sufficient for repression by ammonia or alanine. These results suggest a
      uniform cellular response to nitrogen that is mediated by a different mechanism
      in each case.

PMID- 12218016
TI  - Adaptation of sucrose metabolism in the Escherichia coli wild-type strain EC3132.
AB  - Although Escherichia coli strain EC3132 possesses a chromosomally encoded sucrose
      metabolic pathway, its growth on low sucrose concentrations (5 mM) is unusually
      slow, with a doubling time of 20 h. In this report we describe the subcloning and
      further characterization of the corresponding csc genes and adjacent genes. The
      csc regulon comprises three genes for a sucrose permease, a fructokinase, and a
      sucrose hydrolase (genes cscB, cscK, and cscA, respectively). The genes are
      arranged in two operons and are negatively controlled at the transcriptional
      level by the repressor CscR. Furthermore, csc gene expression was found to be
      cyclic AMP-CrpA dependent. A comparison of the genomic sequences of the E. coli
      strains EC3132, K-12, and O157:H7 in addition to Salmonella enterica serovar
      Typhimurium LT2 revealed that the csc genes are located in a hot spot region for
      chromosomal rearrangements in enteric bacteria. The comparison further indicated
      that the csc genes might have been transferred relatively recently to the E. coli
      wild-type EC3132 at around the time when the different strains of the enteric
      bacteria diverged. We found evidence that a mobile genetic element, which used
      the gene argW for site-specific integration into the chromosome, was probably
      involved in this horizontal gene transfer and that the csc genes are still in the
      process of optimal adaptation to the new host. Selection for such adaptational
      mutants growing faster on low sucrose concentrations gave three different classes
      of mutants. One class comprised cscR(Con) mutations that expressed all csc genes
      constitutively. The second class constituted a cscKo operator mutation, which
      became inducible for csc gene expression at low sucrose concentrations. The third
      class was found to be a mutation in the sucrose permease that caused an increase
      in transport activity.

PMID- 12218017
TI  - Structural maintenance of chromosomes protein of Bacillus subtilis affects
      supercoiling in vivo.
AB  - Structural maintenance of chromosomes (SMC) proteins are found in nearly all
      organisms. Members of this protein family are involved in chromosome condensation
      and sister chromatid cohesion. Bacillus subtilis SMC protein (BsSMC) plays a role
      in chromosome organization and partitioning. To better understand the function of
      BsSMC, we studied the effects of an smc null mutation on DNA supercoiling in
      vivo. We found that an smc null mutant was hypersensitive to the DNA gyrase
      inhibitors coumermycin A1 and norfloxacin. Furthermore, depleting cells of
      topoisomerase I substantially suppressed the partitioning defect of an smc null
      mutant. Plasmid DNA isolated from an smc null mutant was more negatively
      supercoiled than that from wild-type cells. In vivo cross-linking experiments
      indicated that BsSMC was bound to the plasmid. Our results indicate that BsSMC
      affects supercoiling in vivo, most likely by constraining positive supercoils, an
      activity which contributes to chromosome compaction and organization.

PMID- 12218018
TI  - MazG, a nucleoside triphosphate pyrophosphohydrolase, interacts with Era, an
      essential GTPase in Escherichia coli.
AB  - Era is an essential GTPase in Escherichia coli, and Era has been implicated in a
      number of cellular functions. Homologues of Era have been identified in various
      bacteria and some eukaryotes. Using the era gene as bait in the yeast two-hybrid
      system to screen E. coli genomic libraries, we discovered that Era interacts with
      MazG, a protein of unknown function which is highly conserved among bacteria. The
      direct interaction between Era and MazG was also confirmed in vitro, being
      stronger in the presence of GDP than in the presence of GTPgammaS. MazG was
      characterized as a nucleoside triphosphate pyrophosphohydrolase which can
      hydrolyze all eight of the canonical ribo- and deoxynucleoside triphosphates to
      their respective monophosphates and PP(i), with a preference for
      deoxynucleotides. A mazG deletion strain of E. coli was constructed by replacing
      the mazG gene with a kanamycin resistance gene. Unlike mutT, a gene for another
      conserved nucleotide triphosphate pyrophosphohydrolase that functions as a
      mutator gene, the mazG deletion did not result in a mutator phenotype in E. coli.

PMID- 12218019
TI  - Interdependent expression of the ccoNOQP-rdxBHIS loci in Rhodobacter sphaeroides
      2.4.1.
AB  - The rdxBHIS gene cluster of Rhodobacter sphaeroides 2.4.1, located downstream of
      the ccoNOQP operon encoding the cbb(3) cytochrome c oxidase, is required for the
      posttranscriptional modification of the cbb(3) cytochrome c oxidase. The cbb(3)
      cytochrome c oxidase is the main terminal oxidase under microaerobic conditions,
      as well as a component of the signal transduction pathway controlling
      photosynthesis gene expression. Because of the intimate functional and positional
      relationships of the ccoNOQP operon and the rdxBHIS gene cluster, we have
      examined the transcriptional activities of this DNA region in order to understand
      their expression and regulation. Northern blot analysis and reverse transcription
      PCR, together with earlier complementation analysis, suggested that the ccoNOQP
      rdxBHIS cluster is transcribed as ccoNOQP-, ccoNOQP-rdxBH-, rdxBH-, and rdxIS
      specific transcripts. Multiple transcriptional start sites have been identified
      by primer extension analyses: five for ccoN, four for rdxB, and one for rdxI.
      Transcription from P1(N) of ccoN and P1(B) of rdxB is dependent on the presence
      of FnrL. LacZ fusion analysis support the above-described studies, especially the
      importance of FnrL. Expression of the cco-rdx cluster is closely related to
      photosynthesis gene expression, suggesting that transcript stoichiometry and
      presumably the stoichiometry of the gene products are critical factors in
      controlling photosynthesis gene expression.

PMID- 12218020
TI  - Stimulation of menaquinone-dependent electron transfer in the respiratory chain
      of Bacillus subtilis by membrane energization.
AB  - At a pH of <or=7, respiration of Bacillus subtilis cells on endogenous substrates
      shut down almost completely upon addition of an uncoupler (carbonyl cyanide m
      chlorophenylhydrazone [CCCP]) and a K+-ionophore (valinomycin). The same effect
      was observed with cell spheroplasts lacking the cell wall. The concentration of
      CCCP required for 50% inhibition of the endogenous respiration in the presence of
      K+-valinomycin was below 100 nM. Either CCCP or valinomycin alone was much less
      efficient than the combination of the two. The inhibitory effect was easily
      reversible and depended specifically on the H+ and K+ concentrations in the
      medium. Similar inhibition was observed with respect to the reduction of the
      artificial electron acceptors 2,6-dichlorophenolindophenol (DCPIP) and N,N,N',N'
      tetramethyl-p-phenylenediamine cation (TMPD+), which intercept reducing
      equivalents at the level of menaquinol. Oxidation of the reduced DCPIP or TMPD in
      the bacterial cells was not sensitive to uncoupling. The same loss of the
      electron transfer activities as induced by the uncoupling was observed upon
      disruption of the cells during isolation of the membranes; the residual
      activities were not further inhibited by the uncoupler and ionophores. We
      conclude that the menaquinone-dependent electron transfer in the B. subtilis
      respiratory chain is facilitated, thermodynamically or kinetically, by membrane
      energization. A requirement for an energized state of the membrane is not a
      specific feature of succinate oxidation, as proposed in the literature, since it
      was also observed in a mutant of B. subtilis lacking succinate:quinone reductase
      as well as for substrates other than succinate. Possible mechanisms of the energy
      dependent regulation of menaquinone-dependent respiration in B. subtilis are
      discussed.

PMID- 12218021
TI  - Three modifications in the D and T arms of tRNA influence translation in
      Escherichia coli and expression of virulence genes in Shigella flexneri.
AB  - The modified nucleosides 2'-O-methylguanosine, present at position 18 (Gm18), 5
      methyluridine, present at position 54 (m(5)U54), and pseudouridine, present at
      position 55 (Psi55), are located in the D and T arms of tRNAs and are close in
      space in the three-dimensional (3D) structure of this molecule in the bacterium
      Escherichia coli. The formation of these modified nucleosides is catalyzed by the
      products of genes trmH (Gm18), trmA (m(5)U54), and truB (Psi55). The combination
      of trmH, trmA, and truB mutations resulting in lack of these three modifications
      reduced the growth rate, especially at high temperature. Moreover, the lack of
      three modified nucleotides in tRNA induced defects in the translation of certain
      codons, sensitivity to amino acid analog 3,4-dehydro-DL-proline, and an altered
      oxidation of some carbon compounds. The results are consistent with the
      suggestion that these modified nucleosides, two of which directly interact in the
      3D structure of tRNA by forming a hydrogen bond between Psi55 and Gm18, stabilize
      the structure of the tRNA. Moreover, lack of Psi55 in tRNA of human pathogen
      Shigella flexneri leads to a reduced expression of several virulence-associated
      genes.

PMID- 12218022
TI  - Activation of the glnA, glnK, and nac promoters as Escherichia coli undergoes the
      transition from nitrogen excess growth to nitrogen starvation.
AB  - The nitrogen-regulated genes and operons of the Ntr regulon of Escherichia coli
      are activated by the enhancer-binding transcriptional activator NRI approximately
      P (NtrC approximately P). Here, we examined the activation of the glnA, glnK, and
      nac promoters as cells undergo the transition from growth on ammonia to nitrogen
      starvation and examined the amplification of NRI during this transition. The
      results indicate that the concentration of NRI is increased as cells become
      starved for ammonia, concurrent with the activation of Ntr genes that have less-
      efficient enhancers than does glnA. A diauxic growth pattern was obtained when E.
      coli was grown on a low concentration of ammonia in combination with arginine as
      a nitrogen source, consistent with the hypothesis that Ntr genes other than glnA
      become activated only upon amplification of the NRI concentration.

PMID- 12218023
TI  - Context-dependent functions of the PII and GlnK signal transduction proteins in
      Escherichia coli.
AB  - Two closely related signal transduction proteins, PII and GlnK, have distinct
      physiological roles in the regulation of nitrogen assimilation. Here, we examined
      the physiological roles of PII and GlnK when these proteins were expressed from
      various regulated or constitutive promoters. The results indicate that the
      distinct functions of PII and GlnK were correlated with the timing of expression
      and levels of accumulation of the two proteins. GlnK was functionally converted
      into PII when its expression was rendered constitutive and at the appropriate
      level, while PII was functionally converted into GlnK by engineering its
      expression from the nitrogen-regulated glnK promoter. Also, the physiological
      roles of both proteins were altered by engineering their expression from the
      nitrogen-regulated glnA promoter. We hypothesize that the use of two functionally
      identical PII-like proteins, which have distinct patterns of expression, may
      allow fine control of Ntr genes over a wide range of environmental conditions. In
      addition, we describe results suggesting that an additional, unknown mechanism
      may control the cellular level of GlnK.

PMID- 12218024
TI  - Purification, substrate range, and metal center of AtzC: the N-isopropylammelide
      aminohydrolase involved in bacterial atrazine metabolism.
AB  - N-Isopropylammelide isopropylaminohydrolase, AtzC, the third enzyme in the
      atrazine degradation pathway in Pseudomonas sp. strain ADP, catalyzes the
      stoichiometric hydrolysis of N-isopropylammelide to cyanuric acid and
      isopropylamine. The atzC gene was cloned downstream of the tac promoter and
      expressed in Escherichia coli, where the expressed enzyme comprised 36% of the
      soluble protein. AtzC was purified to homogeneity by ammonium sulfate
      precipitation and phenyl column chromatography. It has a subunit size of 44,938
      kDa and a holoenzyme molecular weight of 174,000. The K(m) and k(cat) values for
      AtzC with N-isopropylammelide were 406 micro M and 13.3 s(-1), respectively. AtzC
      hydrolyzed other N-substituted amino dihydroxy-s-triazines, and those with linear
      N-alkyl groups had higher k(cat) values than those with branched alkyl groups.
      Native AtzC contained 0.50 eq of Zn per subunit. The activity of metal-depleted
      AtzC was restored with Zn(II), Fe(II), Mn(II), Co(II), and Ni(II) salts. Cobalt
      substituted AtzC had a visible absorbance band at 540 nm (Delta epsilon = 84 M(
      1) cm(-1)) and exhibited an axial electron paramagnetic resonance (EPR) signal
      with the following effective values: g((x)) = 5.18, g((y)) = 3.93, and g((z)) =
      2.24. Incubating cobalt-AtzC with the competitive inhibitor 5-azacytosine altered
      the effective EPR signal values to g((x)) = 5.11, g((y)) = 4.02, and g((z)) =
      2.25 and increased the microwave power at half saturation at 10 K from 31 to 103
      mW. Under the growth conditions examined, our data suggest that AtzC has a
      catalytically essential, five-coordinate Zn(II) metal center in the active site
      and specifically catalyzes the hydrolysis of intermediates generated during the
      metabolism of s-triazine herbicides.

PMID- 12218025
TI  - Control of inducer accumulation plays a key role in succinate-mediated catabolite
      repression in Sinorhizobium meliloti.
AB  - The symbiotic, nitrogen-fixing bacterium Sinorhizobium meliloti favors succinate
      and related dicarboxylic acids as carbon sources. As a preferred carbon source,
      succinate can exert catabolite repression upon genes needed for the utilization
      of many secondary carbon sources, including the alpha-galactosides raffinose and
      stachyose. We isolated lacR mutants in a genetic screen designed to find S.
      meliloti mutants that had abnormal succinate-mediated catabolite repression of
      the melA-agp genes, which are required for the utilization of raffinose and other
      alpha-galactosides. The loss of catabolite repression in lacR mutants was seen in
      cells grown in minimal medium containing succinate and raffinose and grown in
      succinate and lactose. For succinate and lactose, the loss of catabolite
      repression could be attributed to the constitutive expression of beta-galactoside
      utilization genes in lacR mutants. However, the inactivation of lacR did not
      cause the constitutive expression of alpha-galactoside utilization genes but
      caused the aberrant expression of these genes only when succinate was present. To
      explain the loss of diauxie in succinate and raffinose, we propose a model in
      which lacR mutants overproduce beta-galactoside transporters, thereby
      overwhelming the inducer exclusion mechanisms of succinate-mediated catabolite
      repression. Thus, some raffinose could be transported by the overproduced beta
      galactoside transporters and cause the induction of alpha-galactoside utilization
      genes in the presence of both succinate and raffinose. This model is supported by
      the restoration of diauxie in a lacF lacR double mutant (lacF encodes a beta
      galactoside transport protein) grown in medium containing succinate and
      raffinose. Biochemical support for the idea that succinate-mediated repression
      operates by preventing inducer accumulation also comes from uptake assays, which
      showed that cells grown in raffinose and exposed to succinate have a decreased
      rate of raffinose transport compared to control cells not exposed to succinate.

PMID- 12218026
TI  - Forespore signaling is necessary for pro-sigmaK processing during Bacillus
      subtilis sporulation despite the loss of SpoIVFA upon translational arrest.
AB  - The sigmaK checkpoint coordinates gene expression in the mother cell with
      signaling from the forespore during Bacillus subtilis sporulation. The signaling
      pathway involves SpoIVB, a serine peptidase produced in the forespore, which is
      believed to cross the innermost membrane surrounding the forespore and activate a
      complex of proteins, including BofA, SpoIVFA, and SpoIVFB, located in the
      outermost membrane surrounding the forespore. Activation of the complex allows
      proteolytic processing of pro-sigmaK, and the resulting sigmaK RNA polymerase
      transcribes genes in the mother cell. To investigate activation of the pro-sigmaK
      processing complex, the level of SpoIVFA in extracts of sporulating cells was
      examined by Western blot analysis. The SpoIVFA level decreased when pro-sigmaK
      processing began during sporulation. In extracts of a spoIVB mutant defective in
      forespore signaling, the SpoIVFA level failed to decrease normally and no
      processing of pro-sigmaK was observed. Although these results are consistent with
      a model in which SpoIVFA inhibits processing until the SpoIVB-mediated signal is
      received from the forespore, we discovered that loss of SpoIVFA was insufficient
      to allow processing under certain conditions, including static incubation of the
      culture and continued shaking after the addition of inhibitors of oxidative
      phosphorylation or translation. Under these conditions, loss of SpoIVFA was
      independent of spoIVB. The inability to process pro-sigmaK under these conditions
      was not due to loss of SpoIVFB, the putative processing enzyme, or to a
      requirement for ongoing synthesis of pro-sigmaK. Rather, it was found that the
      requirements for shaking of the culture, for oxidative phosphorylation, and for
      translation could be bypassed by mutations that uncouple processing from
      dependence on forespore signaling. This suggests that ongoing translation is
      normally required for efficient pro-sigmaK processing because synthesis of the
      SpoIVB signal protein is needed to activate the processing complex. When
      translation is blocked, synthesis of SpoIVB ceases, and the processing complex
      remains inactive despite the loss of SpoIVFA. Taken together, the results suggest
      that SpoIVB signaling activates the processing complex by performing another
      function in addition to causing loss of SpoIVFA or by causing loss of SpoIVFA in
      a different way than when translation is blocked. The results also demonstrate
      that the processing machinery can function in the absence of translation or an
      electrochemical gradient across membranes.

PMID- 12218027
TI  - Formation of protoanemonin from 2-chloro-cis,cis-muconate by the combined action
      of muconate cycloisomerase and muconolactone isomerase.
AB  - Muconate cycloisomerases are known to catalyze the reversible conversion of 2
      chloro-cis,cis-muconate by 1,4- and 3,6-cycloisomerization into (4S)-(+)-2-chloro
      and (4R/5S)-(+)-5-chloromuconolactone. 2-Chloromuconolactone is transformed by
      muconolactone isomerase with concomitant dechlorination and decarboxylation into
      the antibiotic protoanemonin. The low k(cat) for this compound compared to that
      for 5-chloromuconolactone suggests that protoanemonin formation is of minor
      importance. However, since 2-chloromuconolactone is the initially predominant
      product of 2-chloromuconate cycloisomerization, significant amounts of
      protoanemonin were formed in reaction mixtures containing large amounts of
      muconolactone isomerase and small amounts of muconate cycloisomerase. Such enzyme
      ratios resemble those observed in cell extracts of benzoate-grown cells of
      Ralstonia eutropha JMP134. In contrast, cis-dienelactone was the predominant
      product formed by enzyme preparations, in which muconolactone isomerase was in
      vitro rate limiting. In reaction mixtures containing chloromuconate
      cycloisomerase and muconolactone isomerase, only minute amounts of protoanemonin
      were detected, indicating that only small amounts of 2-chloromuconolactone were
      formed by cycloisomerization and that chloromuconate cycloisomerase actually
      preferentially catalyzes a 3,6-cycloisomerization.

PMID- 12218029
TI  - Loss of catabolite repression function of HPr, the phosphocarrier protein of the
      bacterial phosphotransferase system, affects expression of the cry4A toxin gene
      in Bacillus thuringiensis subsp. israelensis.
AB  - HPr, the phosphocarrier protein of the bacterial phosphotransferase system,
      mediates catabolite repression of a number of operons in gram-positive bacteria.
      In order to participate in the regulatory process, HPr is activated by
      phosphorylation of a conserved serine-46 residue. To study the potential role of
      HPr in the regulation of Cry4A protoxin synthesis in Bacillus thuringiensis
      subsp. israelensis, we produced a catabolite repression-negative mutant by
      replacing the wild-type copy of the ptsH gene with a mutated copy in which the
      conserved serine residue of HPr was replaced with an alanine. HPr isolated from
      the mutant strain was not phosphorylated at Ser-45 by HPr kinase, but
      phosphorylation at His-14 was found to occur normally. The enzyme I and HPr
      kinase activities of the mutant were not affected. Analysis of the B.
      thuringiensis subsp. israelensis mutant harboring ptsH-S45A in the chromosome
      showed that cry4A expression was derepressed from the inhibitory effect of
      glucose. The mutant strain produced both cry4A and sigma(35) gene transcripts 4 h
      ahead of the parent strain, but there was no effect on sigma(28) synthesis. In
      wild-type B. thuringiensis subsp. israelensis cells, cry4A mRNA was observed from
      12 h onwards, while in the mutant it appeared at 8 h and was produced for a
      longer period. The total amount of cry4A transcripts produced by the mutant was
      higher than by the parent strain. There was a 60 to 70% reduction in the
      sporulation efficiency of the mutant B. thuringiensis subsp. israelensis strain
      compared to the wild-type strain.

PMID- 12218030
TI  - Envelope disorder of Escherichia coli cells lacking phosphatidylglycerol.
AB  - Phosphatidylglycerol, the most abundant acidic phospholipid in Escherichia coli,
      is considered to play specific roles in various cellular processes that are
      essential for cell viability. A null mutation of pgsA, which encodes
      phosphatidylglycerophosphate synthase, does indeed confer lethality. However,
      pgsA null mutants are viable if they lack the major outer membrane lipoprotein
      (Lpp) (lpp mutant) (S. Kikuchi, I. Shibuya, and K. Matsumoto, J. Bacteriol.
      182:371-376, 2000). Here we show that Lpp expressed from a plasmid causes cell
      lysis in a pgsA lpp double mutant. The envelopes of cells harvested just before
      lysis could not be separated into outer and inner membrane fractions by sucrose
      density gradient centrifugation. In contrast, expression of a mutant Lpp
      (LppdeltaK) lacking the COOH-terminal lysine residue (required for covalent
      linking to peptidoglycan) did not cause lysis and allowed for the clear
      separation of the outer and inner membranes. We propose that in pgsA mutants
      LppdeltaK could not be modified by the addition of a diacylglyceryl moiety
      normally provided by phosphatidylglycerol and that this defect caused unmodified
      LppdeltaK to accumulate in the inner membrane. Although LppdeltaK accumulation
      did not lead to lysis, the accumulation of unmodified wild-type Lpp apparently
      led to the covalent linking to peptidoglycan, causing the inner membrane to be
      anomalously anchored to peptidoglycan and eventually leading to lysis. We suggest
      that this anomalous anchoring largely explains a major portion of the nonviable
      phenotypes of pgsA null mutants.

PMID- 12218031
TI  - Identification of the origin of replication of the Mycoplasma pulmonis chromosome
      and its use in oriC replicative plasmids.
AB  - Mycoplasma pulmonis is a natural rodent pathogen, considered a privileged model
      for studying respiratory mycoplasmosis. The complete genome of this bacterium,
      which belongs to the class Mollicutes, has recently been sequenced, but studying
      the role of specific genes requires improved genetic tools. In silico comparative
      analysis of sequenced mollicute genomes indicated the lack of conservation of
      gene order in the region containing the predicted origin of replication (oriC)
      and the existence, in most of the mollicute genomes examined, of putative DnaA
      boxes lying upstream and downstream from the dnaA gene. The predicted M. pulmonis
      oriC region was shown to be functional after cloning it into an artificial
      plasmid and after transformation of the mycoplasma, which was obtained with a
      frequency of 3 x 10(-6) transformants/CFU/ micro g of plasmid DNA. However, after
      a few in vitro passages, this plasmid integrated into the chromosomal oriC
      region. Reduction of this oriC region by subcloning experiments to the region
      either upstream or downstream from dnaA resulted in plasmids that failed to
      replicate in M. pulmonis, except when these two intergenic regions were cloned
      with the tetM determinant as a spacer in between them. An internal fragment of
      the M. pulmonis hemolysin A gene (hlyA) was cloned into this oriC plasmid, and
      the resulting construct was used to transform M. pulmonis. Targeted integration
      of this genetic element into the chromosomal hlyA by a single crossing over,
      which results in the disruption of the gene, could be documented. These
      mycoplasmal oriC plasmids may therefore become valuable tools for investigating
      the roles of specific genes, including those potentially implicated in
      pathogenesis.

PMID- 12218032
TI  - A monocarboxylate permease of Rhizobium leguminosarum is the first member of a
      new subfamily of transporters.
AB  - Amino acid transport by Rhizobium leguminosarum is dominated by two ABC
      transporters, the general amino acid permease (Aap) and the branched-chain amino
      acid permease (Bra). However, mutation of these transporters does not prevent
      this organism from utilizing alanine for growth. An R. leguminosarum permease
      (MctP) has been identified which is required for optimal growth on alanine as a
      sole carbon and nitrogen source. Characterization of MctP confirmed that it
      transports alanine (K(m) = 0.56 mM) and other monocarboxylates such as lactate
      and pyruvate (K(m) = 4.4 and 3.8 micro M, respectively). Uptake inhibition
      studies indicate that propionate, butyrate, alpha-hydroxybutyrate, and acetate
      are also transported by MctP, with the apparent affinity for solutes
      demonstrating a preference for C3-monocarboxylates. MctP has significant sequence
      similarity to members of the sodium/solute symporter family. However, sequence
      comparisons suggest that it is the first characterized permease of a new
      subfamily of transporters. While transport via MctP was inhibited by CCCP, it was
      not apparently affected by the concentration of sodium. In contrast, glutamate
      uptake in R. leguminosarum by the Escherichia coli GltS system did require
      sodium, which suggests that MctP may be proton coupled. Uncharacterized members
      of this new subfamily have been identified in a broad taxonomic range of species,
      including proteobacteria of the beta-subdivision, gram-positive bacteria, and
      archaea. A two-component sensor-regulator (MctSR), encoded by genes adjacent to
      mctP, is required for activation of mctP expression.

PMID- 12218033
TI  - DNA gyrase genes in Mycobacterium tuberculosis: a single operon driven by
      multiple promoters.
AB  - The two genes encoding DNA gyrase in Mycobacterium tuberculosis are present next
      to each other in the genome, with gyrB upstream of gyrA. We show that the primary
      transcript is dicistronic. However, in addition to the principal promoter, there
      are multiple weaker promoters that appear to fine-tune transcription. With these
      and other mycobacterial promoters, we propose consensus promoter sequences for
      two distinct sigma factors. In addition to this, the gyr genes in M.
      tuberculosis, as in other species, are subject to autoregulation, albeit with
      slower kinetics, probably reflecting the slower metabolism of the organism.

PMID- 12218034
TI  - sigmaB modulates virulence determinant expression and stress resistance:
      characterization of a functional rsbU strain derived from Staphylococcus aureus
      8325-4.
AB  - The accessory sigma factor sigmaB controls a general stress response that is
      thought to be important for Staphylococcus aureus survival and may contribute to
      virulence. The strain of choice for genetic studies, 8325-4, carries a small
      deletion in rsbU, which encodes a positive regulator of sigmaB activity.
      Consequently, to enable the role of sigmaB in virulence to be addressed, we
      constructed an rsbU(+) derivative, SH1000, using a method that does not leave
      behind an antibiotic resistance marker. The phenotypic properties of SH1000 (8325
      4 rsbU(+)) were characterized and compared to those of 8325-4, the rsbU mutant,
      parent strain. A recognition site for sigmaB was located in the promoter region
      of katA, the gene encoding the sole catalase of S. aureus, by primer extension
      analysis. However, catalase expression and activity were similar in SH1000 (8325
      4 rsbU(+)), suggesting that this promoter may have a minor role in catalase
      expression under normal conditions. Restoration of sigmaB activity in SH1000
      (8325-4 rsbU(+)) resulted in a marked decrease in the levels of the exoproteins
      SspA and Hla, and this is likely to be mediated by reduced expression of agr in
      this strain. By using Western blotting and a sarA-lacZ reporter assay, the levels
      of SarA were found to be similar in strains 8325-4 and SH1000 (8325-4 rsbU(+))
      and sigB mutant derivatives of these strains. This finding contrasts with
      previous reports that suggested that SarA expression levels are altered when they
      are measured transcriptionally. Inactivation of sarA in each of these strains
      resulted in an expected decrease in agr expression; however, the relative level
      of agr in SH1000 (8325-4 rsbU(+)) remained less than the relative levels in 8325
      4 and the sigB mutant derivatives. We suggest that SarA is not likely to be the
      effector in the overall sigmaB-mediated effect on agr expression.

PMID- 12218035
TI  - Mutational analysis of the Escherichia coli PhoQ sensor kinase: differences with
      the Salmonella enterica serovar Typhimurium PhoQ protein and in the mechanism of
      Mg2+ and Ca2+ sensing.
AB  - The PhoP-PhoQ two-component system plays a role in Mg2+ homeostasis and/or the
      virulence properties of a number of bacterial species. A Salmonella enterica
      serovar Typhimurium PhoQ sensor kinase mutant, in which the threonine at residue
      48 in the periplasmic sensor domain is changed to an isoleucine, was shown
      previously to result in elevated expression of PhoP-activated genes and to affect
      mouse virulence, epithelial cell invasion, and sensitivity to macrophage killing.
      We characterized a complete set of proteins having amino acid substitutions at
      position 48 in the closely related Escherichia coli PhoQ protein. Numerous mutant
      proteins having amino acid substitutions with side chains of various sizes and
      characters displayed signaling phenotypes similar to that of the wild-type
      protein, indicating that interactions mediated by the wild-type threonine side
      chain are not required for normal protein function. Changes to amino acids with
      aromatic side chains had little impact on signaling in response to extracellular
      Mg2+ but resulted in reduced sensitivity to extracellular Ca2+, suggesting that
      the mechanisms of signal transduction in response to these two divalent cations
      are different. Surprisingly, the Ile48 protein displayed a defective phenotype
      rather than the hyperactive phenotype seen with the S. enterica serovar
      Typhimurium protein. We also describe a mutant PhoQ protein lacking the
      extracellular sensor domain with a defect in the ability to activate PhoP. The
      defect does not appear to be due to reduced autokinase activity but rather
      appears to be due to an effect on the stability of the aspartyl-phosphate bond of
      phospho-PhoP.

PMID- 12218036
TI  - Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory
      strains.
AB  - Virulence and immunity are poorly understood in Mycobacterium tuberculosis. We
      sequenced the complete genome of the M. tuberculosis clinical strain CDC1551 and
      performed a whole-genome comparison with the laboratory strain H37Rv in order to
      identify polymorphic sequences with potential relevance to disease pathogenesis,
      immunity, and evolution. We found large-sequence and single-nucleotide
      polymorphisms in numerous genes. Polymorphic loci included a phospholipase C, a
      membrane lipoprotein, members of an adenylate cyclase gene family, and members of
      the PE/PPE gene family, some of which have been implicated in virulence or the
      host immune response. Several gene families, including the PE/PPE gene family,
      also had significantly higher synonymous and nonsynonymous substitution
      frequencies compared to the genome as a whole. We tested a large sample of M.
      tuberculosis clinical isolates for a subset of the large-sequence and single
      nucleotide polymorphisms and found widespread genetic variability at many of
      these loci. We performed phylogenetic and epidemiological analysis to investigate
      the evolutionary relationships among isolates and the origins of specific
      polymorphic loci. A number of these polymorphisms appear to have occurred
      multiple times as independent events, suggesting that these changes may be under
      selective pressure. Together, these results demonstrate that polymorphisms among
      M. tuberculosis strains are more extensive than initially anticipated, and
      genetic variation may have an important role in disease pathogenesis and
      immunity.

PMID- 12218037
TI  - Characterization of amino acid substitutions in KdpA, the K+-binding and 
      translocating subunit of the KdpFABC complex of Escherichia coli.
AB  - When grown under K+ limitation, Escherichia coli induces the K+-translocating
      KdpFABC complex. The stimulation of ATPase activity by NH4+ ions was shown for
      the first time. Substitutions in KdpA, which is responsible for K+ binding and
      translocation, revealed that enzyme complexes KdpA:G232A and KdpA:G232S have
      completely lost their cation selectivity.

PMID- 12218038
TI  - Chromosomal amplification of the Escherichia coli lipB region confers high-level
      resistance to selenolipoic acid.
AB  - One of the mutants (slr7 mutant) of a wild-type Escherichia coli strain resistant
      to selenolipoic acid reported previously (K. E. Reed, T. W. Morris, and J. E.
      Cronan, Jr., Proc. Natl. Acad. Sci. USA 91:3720-3724, 1994) unexpectedly grew on
      minimal medium following transductional introduction of a lipA null mutation. We
      report that the slr7 strain carries a duplication of the lip chromosomal region
      that causes the phenotype of the mutant strain.

PMID- 12218039
TI  - Profiling early osmostress-dependent gene expression in Escherichia coli using
      DNA macroarrays.
AB  - DNA macroarray technology was used to monitor early transcriptional alterations
      of Escherichia coli in response to an osmotic upshift imposed by the addition of
      0.4 M NaCl. Altered mRNA levels of 152 genes were detected; 45 genes showed
      increased expression while the expression of the remaining 107 genes was reduced.
      Northern blot analysis of several selected genes differing in their relative
      expression values confirmed the results obtained by the array technology.

PMID- 12218040
TI  - FepA with globular domain deletions lacks activity.
AB  - TonB-gated transporters have beta-barrels containing an amino-terminal globular
      domain that occludes the interior of the barrel. Mutations in the globular domain
      prevent transport of ligands across the outer membrane. Surprisingly, FepA with
      deletions of the globular domain (amino acids 3 to 150 and 17 to 150) was
      previously reported to retain significant sensitivity to colicins B and D and to
      use ferric enterochelin, all in a TonB-dependent fashion. To further understand
      TonB interaction with the beta-barrel, in the present study, proteins with
      deletions of amino acids 1 to 152, 7 to 152, 20 to 152, and 17 to 150 in fepA
      were constructed and expressed in a deltafepA strain. In contrast to previous
      studies of fepA globular domain deletions, constructs in this study did not
      retain sensitivity to colicin B and conferred only marginal sensitivity to
      colicin D. Consistent with these observations, they failed to bind colicin B and
      detectably cross-link to TonB in vivo. To address this discrepancy, constructs
      were tested in other strains, one of which (RWB18-60) did support activity of the
      FepA globular domain deletion proteins constructed in this study. The
      characteristics of that strain, as well as the strain in which the deltaFhuA
      globular domain mutants were seen to be active, suggests the hypothesis that
      interprotein complementation by two individually nonfunctional proteins restores
      TonB-dependent activity.

PMID- 12218041
TI  - The Escherichia coli metD locus encodes an ABC transporter which includes Abc
      (MetN), YaeE (MetI), and YaeC (MetQ).
AB  - We report that the genes abc, yaeC, and yaeE comprise metD, an Escherichia coli
      locus encoding a DL-methionine uptake system. MetD is an ABC transporter with Abc
      the ATPase, YaeE the permease, and YaeC the likely substrate binding protein.
      Expression of these genes is regulated by L-methionine and MetJ, a common
      repressor of the methionine regulon. We propose to rename abc, yaeE, and yaeC as
      metN, metI, and metQ, respectively.

PMID- 12218042
TI  - Cold shock induction of the cspL gene in Lactobacillus plantarum involves
      transcriptional regulation.
AB  - Fragments of the cspL promoter region were fused to the gusA reporter and
      reintroduced into Lactobacillus plantarum cells, either on multicopy plasmids or
      through single-copy chromosomal integration. beta-Glucuronidase activity and
      primer extension data demonstrate that the cspL promoter is induced in response
      to cold shock and that multicopy constructs quench the induction of the resident
      cspL gene.

PMID- 12218043
TI  - A novel gene that bears a DnaJ motif influences cyanobacterial cell division.
AB  - Transposon Tn5-692 mutagenizes Synechococcus sp. strain PCC 7942 efficiently. The
      predicted product of the gene mutated in the Tn5-692-derived cell division mutant
      FTN2 has an N-terminal DnaJ domain, as have its cyanobacterial and plant
      orthologs. Anabaena sp. strain PCC 7120, when mutated in genes orthologous to
      ftn2 and ftn6, forms akinete-like cells.

PMID- 12218044
TI  - Characterization of a fast cycling ADP-ribosylation factor 6 mutant.
AB  - Studies of GTPase function often employ expression of dominant negative or
      constitutively active mutants. Dominant negative mutants cannot bind GTP and thus
      cannot be activated. Constitutively active mutants cannot hydrolyze GTP and
      therefore accumulate a large pool of GTP-bound GTPase. These mutations block the
      normal cycle of GTP binding, hydrolysis, and release. Therefore, although the
      GTPase-deficient mutants are in the active conformation, they do not fully
      imitate all the actions of the GTPase. This is particularly true for the ADP
      ribosylation factors (ARFs), GTPases that regulate vesicular trafficking events.
      In Ras and Rho GTPases replacement of phenylalanine 28 with a leucine residue
      produces a "fast cycling" mutant that can undergo spontaneous GTP-GDP exchange
      and retains the ability to hydrolyze GTP. Unfortunately this phenylalanine
      residue is not conserved in the ARF family of GTPases. Here we report the design
      and characterization of a novel activated mutant of ARF6, ARF6 T157A. In vitro
      studies show that ARF6 T157A can spontaneously bind and release GTP more quickly
      than the wild-type protein suggesting that it is a fast cycling mutant. This
      mutant has enhanced activity in vivo and induces cortical actin rearrangements in
      HeLa cells and enhanced motility in Madin-Darby canine kidney cells.

PMID- 12218045
TI  - Identification of a JAK2-independent pathway regulating growth hormone (GH)
      stimulated p44/42 mitogen-activated protein kinase activity. GH activation of Ral
      and phospholipase D is Src-dependent.
AB  - We have demonstrated here that growth hormone (GH) stimulates the formation of
      the active GTP-bound form of both RalA and RalB in NIH-3T3 cells. Full activation
      of RalA and RalB by GH required the combined activity of c-Src and JAK2, both
      kinases activated by GH independent of the other. Activation of RalA and RalB by
      growth hormone did not require the activity of JAK2 per se. Ras was also
      activated by GH and was required for the GH-stimulated formation of GTP-bound
      RalA and RalB. Activation of RalA by GH subsequently resulted in increased
      phospholipase D activity and the formation of its metabolite, phosphatidic acid.
      GH-stimulated RalA-phospholipase D-dependent formation of phosphatidic acid was
      required for activation of p44/42 MAPK and subsequent Elk-1-mediated
      transcription stimulated by GH. Thus we report the identification of a JAK2
      independent pathway regulating GH-stimulated p44/42 MAPK activity.

PMID- 12218046
TI  - The translational regulation of lipoprotein lipase by epinephrine involves an RNA
      binding complex including the catalytic subunit of protein kinase A.
AB  - The balance of lipid flux in adipocytes is controlled by the opposing actions of
      lipolysis and lipogenesis, which are controlled primarily by hormone-sensitive
      lipase and lipoprotein lipase (LPL), respectively. Catecholamines stimulate
      adipocyte lipolysis through reversible phosphorylation of hormone-sensitive
      lipase, and simultaneously inhibit LPL activity. However, LPL regulation is
      complex and previous studies have described translational regulation of LPL in
      response to catecholamines because of an RNA-binding protein that interacts with
      the 3'-untranslated region of LPL mRNA. In this study, we identified several
      protein components of an LPL RNA binding complex. Using an LPL RNA affinity
      column, we identified two of the RNA-binding proteins as the catalytic (C)
      subunit of cAMP-dependent protein kinase (PKA), and A kinase anchoring protein
      (AKAP) 121/149, one of the PKA anchoring proteins, which has known RNA binding
      activity. To determine whether the C subunit was involved in LPL translation
      inhibition, the C subunit was depleted from the cytoplasmic extract of
      epinephrine-stimulated adipocytes by immunoprecipitation. This resulted in the
      loss of LPL translation inhibition activity of the extract, along with decreased
      RNA binding activity in a gel shift assay. To demonstrate the importance of the
      AKAPs, inhibition of PKA-AKAP binding with a peptide competitor (HT31) prevented
      epinephrine-mediated inhibition of LPL translation. C subunit kinase activity was
      necessary for LPL RNA binding and translation inhibition, suggesting that the
      phosphorylation of AKAP121/149 or other proteins was an important part of RNA
      binding complex formation. The hormonal activation of PKA results in the
      reversible phosphorylation of hormone-sensitive lipase, which is the primary
      mediator of adipocyte lipolysis. These studies demonstrate a dual role for PKA to
      simultaneously inhibit LPL-mediated lipogenesis through inhibition of LPL
      translation.

PMID- 12218047
TI  - Selective contribution of the twin-arginine translocation pathway to protein
      secretion in Bacillus subtilis.
AB  - The availability of the complete genome sequence of Bacillus subtilis has allowed
      the prediction of all exported proteins of this Gram-positive eubacterium.
      Recently, approximately 180 secretory and 114 lipoprotein signal peptides were
      predicted to direct protein export from the cytoplasm. Whereas most exported
      proteins appear to use the Sec pathway, 69 of these proteins could potentially
      use the Tat pathway, as their signal peptides contain RR- or KR-motifs. In the
      present studies, proteomic techniques were applied to verify how many
      extracellular B. subtilis proteins follow the Tat pathway. Strikingly, the
      extracellular accumulation of 13 proteins with potential RR/KR-signal peptides
      was Tat-independent, showing that their RR/KR-motifs are not recognized by the
      Tat machinery. In fact, only the phosphodiesterase PhoD was shown to be secreted
      in a strictly Tat-dependent manner. Sodium azide-inhibition of SecA strongly
      affected the extracellular appearance of de novo synthesized proteins, including
      the lipase LipA and two other proteins with predicted RR/KR-signal peptides. The
      SecA-dependent export of pre-LipA is particularly remarkable, because its RR
      signal peptide conforms well to stringent criteria for the prediction of Tat
      dependent export in Escherichia coli. Taken together, our observations show that
      the Tat pathway makes a highly selective contribution to the extracellular
      proteome of B. subtilis.

PMID- 12218048
TI  - The role of p42/44 MAPK and protein kinase B in connective tissue growth factor
      induced extracellular matrix protein production, cell migration, and actin
      cytoskeletal rearrangement in human mesangial cells.
AB  - Connective tissue growth factor (CTGF) is a member of an emerging family of
      immediate-early gene products that coordinate complex biological processes during
      differentiation and tissue repair. Here we describe the role of CTGF in integrin
      mediated adhesive signaling and the production of extracellular matrix components
      in human mesangial cells. The addition of CTGF to primary mesangial cells induced
      fibronectin production, cell migration, and cytoskeletal rearrangement. These
      functional responses were associated with recruitment of Src and phosphorylation
      of p42/44 MAPK and protein kinase B. The inhibition of CTGF-induced p42/44 MAPK
      or phosphatidylinositol 3-kinase (PI3K)/protein kinase B pathway activities
      abrogated the induction of fibronectin expression. In addition, anti-beta(3)
      integrin antibodies attenuated the activation of both the p42/44 MAPK and protein
      kinase B and the increase in fibronectin levels. CTGF also induced mesangial cell
      migration via a beta(3) integrin-dependent mechanism that was similarly sensitive
      to the inhibition of the p42/44 MAPK and PI3K pathways, and it promoted the
      adhesion of the mesangial cells to type I collagen via up-regulation of alpha(1)
      integrin. Transient actin cytoskeletal disassembly was observed following
      treatment with the ligand over the course of a 24-h period. CTGF induced the loss
      of focal adhesions from the mesangial cell as evidenced by the loss of punctate
      vinculin. However, these processes are p42/44 MAPK and PI3K pathway-independent.
      Our data support the hypothesis that CTGF mediates a number of its biological
      effects by the induction of signaling processes via beta(3) integrin. However,
      others such as actin cytoskeleton disassembly are modulated in a beta(3)
      integrin/MAPK/PI3K-independent manner, indicating that CTGF is a complex
      pleiotropic factor with the potential to amplify primary pathophysiological
      responses.

PMID- 12218049
TI  - Cyclic AMP induces transactivation of the receptors for epidermal growth factor
      and nerve growth factor, thereby modulating activation of MAP kinase, Akt, and
      neurite outgrowth in PC12 cells.
AB  - In PC12 cells, a well studied model for neuronal differentiation, an elevation in
      the intracellular cAMP level increases cell survival, stimulates neurite
      outgrowth, and causes activation of extracellular signal-regulated protein kinase
      1 and 2 (ERK1/2). Here we show that an increase in the intracellular cAMP
      concentration induces tyrosine phosphorylation of two receptor tyrosine kinases,
      i.e. the epidermal growth factor (EGF) receptor and the high affinity receptor
      for nerve growth factor (NGF), also termed Trk(A). cAMP-induced tyrosine
      phosphorylation of the EGF receptor is rapid and correlates with ERK1/2
      activation. It occurs also in Panc-1, but not in human mesangial cells. cAMP
      induced tyrosine phosphorylation of the NGF receptor is slower and correlates
      with Akt activation. Inhibition of EGF receptor tyrosine phosphorylation, but not
      of the NGF receptor, reduces cAMP-induced neurite outgrowth. Expression of
      dominant-negative Akt does not abolish cAMP-induced survival in serum-free media,
      but increases cAMP-induced ERK1/2 activation and neurite outgrowth. Together, our
      results demonstrate that cAMP induces dual signaling in PC12 cells:
      transactivation of the EGF receptor triggering the ERK1/2 pathway and neurite
      outgrowth; and transactivation of the NGF receptor promoting Akt activation and
      thereby modulating ERK1/2 activation and neurite outgrowth.

PMID- 12218050
TI  - Role of two dileucine-like motifs in insulin receptor anchoring to microvilli.
AB  - In the absence of ligand, the insulin receptor is maintained on microvilli on the
      cell surface. A dileucine motif (LL(986-987)) is necessary but not sufficient for
      this anchoring, which also required the presence of additional sequence(s)
      downstream of position 1000. The aim of the present study was to identify this
      (these) additional sequence(s). First, exons 16 or 17 were fused to the
      extracellular and transmembrane domains of complement receptor 1 and stably
      expressed in Chinese hamster ovary cells. Results obtained indicate that exon 17
      is sufficient for anchoring to microvilli. Second, analysis of insulin receptor
      mutants truncated within exon 17 demonstrated that whereas receptors truncated at
      position 1000 showed no preferential association with microvilli, receptors
      truncated at position 1012 displayed a level of association identical to that of
      the full-length insulin receptor. Third, mutation of a diisoleucine motif
      (II(1006-1007)) present within this 12-amino acid stretch abrogated the
      preferential association of the receptor with microvilli. These results indicate
      that the domain required for association of insulin receptor with microvilli is
      contained within the region encoded by exon 17 and that, within this sequence,
      two dileucine-like motifs (LL(986-987) and II(1006-1007)) play a crucial role.

PMID- 12218051
TI  - Inhibitors of protein-disulfide isomerase prevent cleavage of disulfide bonds in
      receptor-bound glycoprotein 120 and prevent HIV-1 entry.
AB  - We previously reported that monoclonal antibodies to protein-disulfide isomerase
      (PDI) and other membrane-impermeant PDI inhibitors prevented HIV-1 infection. PDI
      is present at the surface of HIV-1 target cells and reduces disulfide bonds in a
      model peptide attached to the cell membrane. Here we show that soluble PDI
      cleaves disulfide bonds in recombinant envelope glycoprotein gp120 and that gp120
      bound to the surface receptor CD4 undergoes a disulfide reduction that is
      prevented by PDI inhibitors. Concentrations of inhibitors that prevent this
      reduction and inhibit the cleavage of surface-bound disulfide conjugate prevent
      infection at the level of HIV-1 entry. The entry of HIV-1 strains differing in
      their coreceptor specificities is similarly inhibited, and so is the reduction of
      gp120 bound to CD4 of coreceptor-negative cells. PDI inhibitors also prevent HIV
      envelope-mediated cell-cell fusion but have no effect on the entry of HIV-1
      pseudo-typed with murine leukemia virus envelope. Importantly, PDI coprecipitates
      with both soluble and cellular CD4. We propose that a PDI.CD4 association at the
      cell surface enables PDI to reach CD4-bound virus and to reduce disulfide bonds
      present in the domain of gp120 that binds to CD4. Conformational changes
      resulting from the opening of gp120-disulfide loops may drive the processes of
      virus-cell and cell-cell fusion. The biochemical events described identify new
      potential targets for anti-HIV agents.

PMID- 12218052
TI  - Protein-disulfide isomerase-mediated reduction of two disulfide bonds of HIV
      envelope glycoprotein 120 occurs post-CXCR4 binding and is required for fusion.
AB  - The human immunodeficiency virus (HIV) envelope (Env) glycoprotein (gp) 120 is a
      highly disulfide-bonded molecule that attaches HIV to the lymphocyte surface
      receptors CD4 and CXCR4. Conformation changes within gp120 result from binding
      and trigger HIV/cell fusion. Inhibition of lymphocyte surface-associated protein
      disulfide isomerase (PDI) blocks HIV/cell fusion, suggesting that redox changes
      within Env are required. Using a sensitive assay based on a thiol reagent, we
      show that (i) the thiol content of gp120, either secreted by mammalian cells or
      bound to a lymphocyte surface enabling CD4 but not CXCR4 binding, was 0.5-1 pmol
      SH/pmol gp120 (SH/gp120), whereas that of gp120 after its interaction with a
      surface enabling both CD4 and CXCR4 binding was raised to 4 SH/gp120; (ii) PDI
      inhibitors prevented this change; and (iii) gp120 displaying 2 SH/gp120 exhibited
      CD4 but not CXCR4 binding capacity. In addition, PDI inhibition did not impair
      gp120 binding to receptors. We conclude that on average two of the nine
      disulfides of gp120 are reduced during interaction with the lymphocyte surface
      after CXCR4 binding prior to fusion and that cell surface PDI catalyzes this
      process. Disulfide bond restructuring within Env may constitute the molecular
      basis of the post-receptor binding conformational changes that induce fusion
      competence.

PMID- 12218053
TI  - A coregulatory role for the TRAP-mediator complex in androgen receptor-mediated
      gene expression.
AB  - The human thyroid hormone receptor-associated protein (TRAP)-Mediator complex was
      originally identified as a large multimeric complex that copurifies with the
      thyroid hormone receptor (TR) from HeLa cells and markedly enhances TR-mediated
      transcription in vitro. More recent studies have implicated TRAP-Mediator as a
      coactivator for a broad range of nuclear hormone receptors as well as other
      classes of transcriptional activators. Here we present evidence that TRAP
      Mediator plays a functional role in androgen receptor (AR)-mediated
      transcription. We show that several subunits of the complex ligand-dependently
      coimmunoprecipitate with AR from both prostate cancer LNCaP cells and from HeLa
      cells stably transfected with AR. The 220-kDa subunit of the complex (TRAP220)
      can contact the ligand-binding domain of AR in vitro, possibly implicating
      TRAP220 involvement in targeting AR to the holocomplex. Consistent with a TRAP
      Mediator coactivator role, transient overexpression of the TRAP220, TRAP170, and
      TRAP100 subunits enhanced ligand-dependent transcription by AR in cultured cells.
      Finally, chromatin immunoprecipitation assays show that TRAP220 is recruited to
      the androgen-responsive prostate-specific antigen gene promoter in vivo in ligand
      stimulated LNCaP cells. Collectively, these data suggest that TRAP-Mediator may
      play an important coregulatory role in AR-mediated gene expression.

PMID- 12218055
TI  - Regulation of integrin function by CD47 ligands. Differential effects on alpha
      vbeta 3 and alpha 4beta1 integrin-mediated adhesion.
AB  - We examined the regulation of alpha4beta1 integrin function in melanoma cells and
      T cells by ligands of CD47. A CD47 antibody (B6H12) that inhibited alphavbeta3
      mediated adhesion of melanoma cells induced by CD47-binding peptides from
      thrombospondin-1 directly stimulated alpha4beta1-mediated adhesion of the same
      cells to vascular cell adhesion molecule-1 and N-terminal regions of
      thrombospondin-1 or thrombospondin-2. B6H12 also stimulated alpha4beta1- as well
      as alpha2beta1- and alpha5beta1-mediated adhesion of CD47-expressing T cells but
      not of CD47-deficient T cells. alpha4beta1 and CD47 co-purified as a detergent
      stable complex on a CD47 antibody affinity column. CD47-binding peptides based on
      C-terminal sequences of thrombospondin-1 also specifically enhanced adhesion of
      melanoma cells and T cells to alpha4beta1 ligands. Unexpectedly, activation of
      alpha4beta1 function by the thrombospondin-1 CD47-binding peptides also occurred
      in CD47-deficient T cells. CD47-independent activation of alpha4beta1 required
      the Val-Val-Met (VVM) motif of the peptides and was sensitive to inhibition by
      pertussis toxin. These results indicate that activation of alpha4beta1 by the
      CD47 antibody B6H12 and by VVM peptides occurs by different mechanisms. The
      antibody directly activates a CD47-alpha4beta1 complex, whereas VVM peptides may
      target an unidentified Gi-linked receptor that regulates alpha4beta1.

PMID- 12218054
TI  - Protein kinase C-alpha and ERK1/2 mediate mitochondrial dysfunction, decreases in
      active Na+ transport, and cisplatin-induced apoptosis in renal cells.
AB  - Initiation of apoptosis by many agents is preceded by mitochondrial dysfunction
      and depolarization of the mitochondrial inner membrane. Here we demonstrate that,
      in renal proximal tubular cells (RPTC), cisplatin induces mitochondrial
      dysfunction associated with hyperpolarization of the mitochondrial membrane and
      that these events are mediated by protein kinase C (PKC)-alpha and ERK1/2.
      Cisplatin induced sustained decreases in RPTC respiration, oxidative
      phosphorylation, and increases in the mitochondrial transmembrane potential
      (deltaPsi(m)), which were preceded by the inhibition of F(0)F(1)-ATPase and
      cytochrome c release from the mitochondria, accompanied by caspase-3 activation,
      and followed by RPTC apoptosis. Cisplatin also decreased active Na+ transport as
      a result, in part, of the inhibition of Na+/K(+)-ATPase. These changes were
      preceded by PKC-alpha and ERK1/2 activation. Inhibition of cisplatin-induced PKC
      alpha and ERK1/2 activation using Go6976 and PD98059, respectively, abolished
      increases in deltaPsi(m), diminished decreases in oxidative phosphorylation,
      active Na+ transport, and decreased caspase-3 activation without blocking
      cytochrome c release. Caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp
      fluoromethylketone (zVAD-fmk) did not prevent increases in deltaPsi(m).
      Furthermore, inhibition of PKC-alpha did not prevent cisplatin-induced ERK1/2
      activation. We concluded that in RPTC: 1) cisplatin-induced mitochondrial
      dysfunction, decreases in active Na+ transport, and apoptosis are mediated by PKC
      alpha and ERK1/2; 2) PKC-alpha and ERK1/2 mediate activation of caspase-3 by
      acting downstream of cytochrome c release from mitochondria; and 3) ERK1/2
      activation by cisplatin occurs through a PKC-alpha-independent pathway.

PMID- 12218056
TI  - Structural basis for the inhibition of the biosynthesis of biotin by the
      antibiotic amiclenomycin.
AB  - The antibiotic amiclenomycin blocks the biosynthesis of biotin by inhibiting the
      pyridoxal-phosphate-dependent enzyme diaminopelargonic acid synthase.
      Inactivation of the enzyme is stereoselective, i.e. the cis isomer of
      amiclenomycin is a potent inhibitor, whereas the trans isomer is much less
      reactive. The crystal structure of the complex of the holoenzyme and
      amiclenomycin at 1.8 A resolution reveals that the internal aldimine linkage
      between the cofactor and the side chain of the catalytic residue Lys-274 is
      broken. Instead, a covalent bond is formed between the 4-amino nitrogen of
      amiclenomycin and the C4' carbon atom of pyridoxal-phosphate. The electron
      density for the bound inhibitor suggests that aromatization of the cyclohexadiene
      ring has occurred upon formation of the covalent adduct. This process could be
      initiated by proton abstraction at the C4 carbon atom of the cyclohexadiene ring,
      possibly by the proximal side chain of Lys-274, leading to the tautomer Schiff
      base followed by the removal of the second allylic hydrogen. The carboxyl tail of
      the amiclenomycin moiety forms a salt link to the conserved residue Arg-391 in
      the substrate-binding site. Modeling suggests steric hindrance at the active site
      as the determinant of the weak inhibiting potency of the trans isomer.

PMID- 12218057
TI  - Crystal structure of a C-terminal fragment of growth arrest-specific protein
      Gas6. Receptor tyrosine kinase activation by laminin G-like domains.
AB  - Receptor tyrosine kinases of the Axl family are activated by Gas6, the product of
      growth arrest-specific gene 6. Gas6-Axl signaling is implicated in cell survival,
      adhesion, and migration. The receptor-binding site of Gas6 is located within a C
      terminal pair of laminin G-like (LG) domains that do not resemble any other
      receptor tyrosine kinase ligand. We report the crystal structure at 2.2-A
      resolution of a Gas6 fragment spanning both LG domains (Gas6-LG). The structure
      reveals a V-shaped arrangement of LG domains strengthened by an interdomain
      calcium-binding site. LG2 of Gas6-LG contains two unusual features: an alpha
      helix cradled by one edge of the LG beta-sandwich and a conspicuous patch of
      surface-exposed hydrophobic residues. Mutagenesis of some residues in this patch
      reduces Gas6-LG binding to the extracellular domain of Axl as well as Axl
      activation in glioblastoma cells, identifying a component of the receptor-binding
      site of Gas6.

PMID- 12218058
TI  - Post-translational modification of bone morphogenetic protein-1 is required for
      secretion and stability of the protein.
AB  - Bone morphogenetic protein (BMP)-1 is a glycosylated metalloproteinase that is
      fundamental to the synthesis of a normal extracellular matrix because it cleaves
      type I procollagen, as well as other precursor proteins. Sequence analysis
      suggests that BMP-1 has six potential N-linked glycosylation sites (i.e. NXS/T)
      namely: Asn(91) (prodomain), Asn(142) (metalloproteinase domain), Asn(332) and
      Asn(363) (CUB1 domain), Asn(599) (CUB3 domain), and Asn(726) in the C-terminal
      specific domain. In this study we showed that all these sites are N-glycosylated
      with complex-type oligosaccharides containing sialic acid, except Asn(726)
      presumably because proline occurs immediately C-terminal of threonine in the
      consensus sequence. Recombinant BMP-1 molecules lacking all glycosylation sites
      or the three CUB-specific sites were not secreted. BMP-1 lacking CUB
      glycosylation was translocated to the proteasome for degradation. BMP-1 molecules
      lacking individual glycosylation sites were efficiently secreted and exhibited
      full procollagen C-proteinase activity, but N332Q and N599Q exhibited a slower
      rate of cleavage. BMP-1 molecules lacking any one of the CUB-specific
      glycosylation sites were sensitive to thermal denaturation. The study showed that
      the glycosylation sites in the CUB domains of BMP-1 are important for secretion
      and stability of the molecule.

PMID- 12218059
TI  - Enzymatic synthesis in vitro of the disulfated disaccharide unit of corneal
      keratan sulfate.
AB  - Among the enzymes of the carbohydrate sulfotransferase family, human corneal
      GlcNAc 6-O-sulfotransferase (hCGn6ST, also known as human GlcNAc6ST-5/GST4beta)
      and human intestinal GlcNAc 6-O-sulfotransferase (hIGn6ST or human GlcNAc6ST
      3/GST4alpha) are highly homologous. In the mouse, intestinal GlcNAc 6-O
      sulfotransferase (mIGn6ST or mouse GlcNAc6ST-3/GST4) is the only orthologue of
      hCGn6ST and hIGn6ST. In the previous study, we found that hCGn6ST and mIGn6ST,
      but not hIGn6ST, have sulfotransferase activity to produce keratan sulfate
      (Akama, T. O., Nakayama, J., Nishida, K., Hiraoka, N., Suzuki, M., McAuliffe, J.,
      Hindsgaul, O., Fukuda, M., and Fukuda, M. N. (2001) J. Biol. Chem. 276, 16271
      16278). In this study, we analyzed the substrate specificities of these
      sulfotransferases in vitro using synthetic carbohydrate substrates. We found that
      all three sulfotransferases can transfer sulfate to the nonreducing terminal
      GlcNAc of short carbohydrate substrates. Both hCGn6ST and mIGn6ST, but not
      hIGn6ST, transfer sulfate to longer carbohydrate substrates that have poly-N
      acetyllactosamine structures, suggesting the involvement of hCGn6ST and mIGn6ST
      in production of keratan sulfate. To clarify further the involvement of hCGn6ST
      in biosynthesis of keratan sulfate, we reconstituted the biosynthetic pathway in
      vitro by sequential enzymatic treatment of a synthetic carbohydrate substrate.
      Using four enzymes, beta1,4-galactosyltransferase-I, beta1,3-N
      acetylglucosaminyltransferase-2, hCGn6ST, and keratan sulfate Gal 6-O
      sulfotransferase, we were able to synthesize in vitro a product that conformed to
      the basic structural unit of keratan sulfate. Based on these results, we propose
      a biosynthetic pathway for N-linked keratan sulfate on corneal proteoglycans.

PMID- 12218060
TI  - Disruption of the endothelial cell protein C receptor gene in mice causes
      placental thrombosis and early embryonic lethality.
AB  - The endothelial cell protein C receptor (EPCR) is a type 1 transmembrane protein
      found primarily on endothelium that binds both protein C and activated protein C
      with similar affinity. EPCR augments the activation of protein C by the thrombin
      thrombomodulin complex. To determine the physiological importance of EPCR, we
      generated EPCR-deficient mice by homologous targeting in embryonic stem cells.
      Genotyping of progeny obtained from EPCR(+/-) interbreeding indicated that EPCR(
      /-) embryos died on or before embryonic day 10.5 (E10.5). Reverse transcriptase
      PCR confirmed the absence of EPCR mRNA in EPCR(-/-) embryos. EPCR(-/-) embryos
      removed from extra-embryonic membranes and tissues at day E7.5 and cultured in
      vitro developed beyond E10.5, suggesting a role for EPCR in the normal function
      of the placenta and/or at the materno-embryonic interface. Immunohistochemistry
      revealed the lack of EPCR in trophoblast giant cells of EPCR(-/-) embryos. These
      cells, which normally express EPCR, are in direct contact with the maternal
      circulation and its clotting factors. In EPCR(-/-) embryos, greatly increased
      fibrin deposition was detected around these cells. To prevent this fibrin
      deposition, EPCR(+/-)-crossed female mice received a daily subcutaneous injection
      of enoxaparin through pregnancy. Although some EPCR(-/-) embryos were rescued
      from midgestational lethality, this regimen yielded no EPCR(-/-) pups. We
      conclude that EPCR is essential for normal embryonic development. Moreover, EPCR
      plays a key role in preventing thrombosis at the maternal-embryonic interface.

PMID- 12218061
TI  - Synthetic Smac/DIABLO peptides enhance the effects of chemotherapeutic agents by
      binding XIAP and cIAP1 in situ.
AB  - Inhibitor of apoptosis proteins (IAPs) interact with and inhibit caspases-3, -7,
      and -9. This interaction can be inhibited by Smac/DIABLO, a polypeptide released
      from mitochondria upon initiation of the apoptotic signaling process. Here we
      demonstrate that the first 4-8 N-terminal amino acids of Smac/DIABLO fused to the
      Drosophila antennapaedia penetratin sequence, a carrier peptide, enhance the
      induction of apoptosis and long term antiproliferative effects of diverse
      antineoplastic agents including paclitaxel, etoposide, 7-ethyl-10
      hydroxycamptothecin (SN-38), and doxorubicin in MCF-7 breast cancer cells.
      Similar effects were observed in additional breast cancer and immortalized
      cholangiocyte cell lines. Further analysis demonstrated that the Smac-penetratin
      fusion peptide crossed the cellular membrane, bound XIAP and cIAP1, displaced
      caspase-3 from cytoplasmic aggregates, and enhanced drug-induced caspase action
      in situ. These studies demonstrate that inhibition of IAP proteins can modulate
      the efficacy of antineoplastic agents.

PMID- 12218062
TI  - Ubiquitin modification of serum and glucocorticoid-induced protein kinase-1 (SGK
      1).
AB  - The serum and glucocorticoid-induced protein kinase gene (sgk-1) encodes a
      multifunctional kinase that can be phosphorylated and activated through a
      phosphatidylinositol 3-kinase-dependent signaling pathway. In many cell types,
      endogenous SGK-1 steady-state protein levels are very low but can be acutely up
      regulated after glucocorticoid receptor-mediated transcriptional activation; in
      breast epithelial and cancer cell lines, this up-regulation is associated with
      promotion of cell survival. We and others have noted that ectopically introduced
      full-length SGK-1 is poorly expressed, although SGK-1 lacking the first 60 amino
      acids (delta60SGK-1) is expressed at much higher-fold protein levels than wild
      type SGK-1 in both human embryonic kidney 293T and MCF10A mammary epithelial
      cells. In this report, we demonstrate for the first time that the low steady
      state expression level of SGK-1 is due to polyubiquitination and subsequent
      degradation by the 26S proteasome. Deletion of the amino-terminal 60 amino acids
      of SGK-1 results in a mutant SGK-1 protein that is neither efficiently
      polyubiquitinated nor degraded by the 26S proteasome, accounting for the higher
      steady-state levels of the truncated protein. We also demonstrate that a subset
      of SGK-1 localizes to the plasma membrane and that the polyubiquitin-modified SGK
      1 localizes to a membrane-associated fraction of the cell. Taken together, these
      data suggest that a significant fraction of SGK-1 is membrane-associated and
      ubiquitinated. These findings are consistent with the recently described role of
      SGK-1 in phosphorylating the membrane-associated protein Nedd4-2 and the integral
      membrane Na+/H+ exchanger isoform 3 (NHE3) and suggest a novel mechanism of
      regulation of SGK-1.

PMID- 12218063
TI  - Effects on collagen VI mRNA stability and microfibrillar assembly of three COL6A2
      mutations in two families with Ullrich congenital muscular dystrophy.
AB  - We recently reported a severe deficiency in collagen type VI, resulting from
      recessive mutations of the COL6A2 gene, in patients with Ullrich congenital
      muscular dystrophy. Their parents, who are all carriers of one mutant allele, are
      unaffected, although heterozygous mutations in collagen VI caused Bethlem
      myopathy. Here we investigated the consequences of three COL6A2 mutations in
      fibroblasts from patients and their parents in two Ullrich families. All three
      mutations lead to nonsense-mediated mRNA decay. However, very low levels of
      undegraded mutant mRNA remained in patient B with compound heterozygous mutations
      at the distal part of the triple-helical domain, resulting in deposition of
      abnormal microfibrils that cannot form extensive networks. This observation
      suggests that the C-terminal globular domain is not essential for triple-helix
      formation but is critical for microfibrillar assembly. In all parents, the COL6A2
      mRNA levels are reduced to 57-73% of the control, but long term collagen VI
      matrix depositions are comparable with that of the control. The almost complete
      absence of abnormal protein and near-normal accumulation of microfibrils in the
      parents may account for their lack of myopathic symptoms.

PMID- 12218064
TI  - Is the GehD lipase from Staphylococcus epidermidis a collagen binding adhesin?
AB  - The opportunistic human pathogen Staphylococcus epidermidis is the major cause of
      nosocomial biomaterial infections. S. epidermidis has the ability to attach to
      indwelling materials coated with extracellular matrix proteins such as
      fibrinogen, fibronectin, vitronectin, and collagen. To identify the proteins
      necessary for S. epidermidis attachment to collagen, we screened an expression
      library using digoxigenin-labeled collagen as well as two monoclonal antibodies
      generated against the Staphylococcus aureus collagen-adhesin, Cna, as probes.
      These monoclonal antibodies recognize collagen binding epitopes on the surface of
      S. aureus and S. epidermidis cells. Using this approach, we identified GehD, the
      extracellular lipase originally found in S. epidermidis 9, as a collagen-binding
      protein. Despite the monoclonal antibody cross-reactivity, the GehD amino acid
      sequence and predicted structure are radically different from those of Cna. The
      mature GehD circular dichroism spectra differs from that of Cna but strongly
      resembles that of a mammalian cell-surface collagen binding receptor, known as
      the alpha(1) integrin I domain, suggesting that they have similar secondary
      structures. The GehD protein is translated as a preproenzyme, secreted, and post
      translationally processed into mature lipase. GehD does not have the conserved
      LPXTG C-terminal motif present in cell wall-anchored proteins, but it can be
      detected in lysostaphin cell wall extracts. A recombinant version of mature GehD
      binds to collagens type I, II, and IV adsorbed onto microtiter plates in a dose
      dependent saturable manner. Recombinant, mature GehD protein and anti-GehD
      antibodies can inhibit the attachment of S. epidermidis to immobilized collagen.
      These results provide evidence that GehD may be a bi-functional molecule, acting
      not only as a lipase but also as a cell surface-associated collagen adhesin.

PMID- 12218065
TI  - A calmodulin-binding/CGCG box DNA-binding protein family involved in multiple
      signaling pathways in plants.
AB  - We reported earlier that the tobacco early ethylene-responsive gene NtER1 encodes
      a calmodulin-binding protein (Yang, T., and Poovaiah, B. W. (2000) J. Biol. Chem.
      275, 38467-38473). Here we demonstrate that there is one NtER1 homolog as well as
      five related genes in Arabidopsis. These six genes are rapidly and differentially
      induced by environmental signals such as temperature extremes, UVB, salt, and
      wounding; hormones such as ethylene and abscisic acid; and signal molecules such
      as methyl jasmonate, H(2)O(2), and salicylic acid. Hence, they were designated as
      AtSR1-6 (Arabidopsis thaliana signal-responsive genes). Ca(2+)/calmodulin binds
      to all AtSRs, and their calmodulin-binding regions are located on a conserved
      basic amphiphilic alpha-helical motif in the C terminus. AtSR1 targets the
      nucleus and specifically recognizes a novel 6-bp CGCG box (A/C/G)CGCG(G/T/C). The
      multiple CGCG cis-elements are found in promoters of genes such as those involved
      in ethylene signaling, abscisic acid signaling, and light signal perception. The
      DNA-binding domain in AtSR1 is located on the N-terminal 146 bp where all AtSR1
      related proteins share high similarity but have no similarity to other known DNA
      binding proteins. The calmodulin-binding nuclear proteins isolated from wounded
      leaves exhibit specific CGCG box DNA binding activities. These results suggest
      that the AtSR gene family encodes a family of calmodulin-binding/DNA-binding
      proteins involved in multiple signal transduction pathways in plants.

PMID- 12218066
TI  - Localization of carbohydrate attachment sites and disulfide bridges in limulus
      alpha 2-macroglobulin. Evidence for two forms differing primarily in their bait
      region sequences.
AB  - The primary structure determination of the dimeric invertebrate alpha(2)
      macroglobulin (alpha(2)M) from Limulus polyphemus has been completed by
      determining its sites of glycosylation and disulfide bridge pattern. Of seven
      potential glycosylation sites for N-linked glycosylation, six (Asn(275),
      Asn(307), Asn(866), Asn(896), Asn(1089), and Asn(1145)) carry common glucosamine
      based carbohydrates groups, whereas one (Asn(80)) carries a carbohydrate chain
      containing both glucosamine and galactosamine. Nine disulfide bridges, which are
      homologues with bridges in human alpha(2)M, have been identified (Cys(228)
      Cys(269), Cys(456)-Cys(580), Cys(612)-Cys(799), Cys(657)-Cys(707), Cys(849)
      Cys(876), Cys(874)-Cys(910), Cys(946)-Cys(1328), Cys(1104)-Cys(1155), and
      Cys(1362)-Cys(1475)). In addition to these bridges, Limulus alpha(2)M contains
      three unique bridges that connect Cys(361) and Cys(382), Cys(1370) and Cys(1374),
      respectively, and Cys(719) in one subunit with the same residue in the other
      subunit of the dimer. The latter bridge forms the only interchain disulfide
      bridge in Limulus alpha(2)M. The location of this bridge within the bait region
      is discussed and compared with other alpha-macroglobulins. Several peptides
      identified in the course of determining the disulfide bridge pattern provided
      evidence for the existence of two forms of Limulus alpha(2)M. The two forms have
      a high degree of sequence identity, but they differ extensively in large parts of
      their bait regions suggesting that they have different inhibitory spectra. The
      two forms (Limulus alpha(2)M-1 and -2) are most likely present in an
      approximately 2:1 ratio in the hemolymph of each animal, and they can be
      partially separated on a Mono Q column at pH 7.4 by applying a shallow gradient
      of NaCl.

PMID- 12218067
TI  - Structural and kinetic studies of sugar binding to galactose mutarotase from
      Lactococcus lactis.
AB  - Galactose mutarotase catalyzes the conversion of beta-D-galactose to alpha-D
      galactose in the Leloir pathway for galactose metabolism. The high resolution x
      ray structure of the dimeric enzyme from Lactococcus lactis was recently solved
      and shown to be topologically similar to the 18-stranded, anti-parallel beta
      motif observed for domain 5 of beta-galactosidase. In addition to determining the
      overall molecular fold of galactose mutarotase, this initial investigation also
      provided a detailed description of the electrostatic interactions between the
      enzyme and its physiologically relevant substrate, galactose. Specifically, the
      side chains of His-96 and His-170 were shown to be located within hydrogen
      bonding distance to the C-5 oxygen of the substrate, while the carboxylate of Glu
      304 was positioned near the C-1 hydroxyl group of the sugar. On the basis of this
      initial study, a possible role for Glu-304 as the general acid/base group in
      catalysis was put forth. Here we describe the combined x-ray crystallographic and
      kinetic analyses of L. lactis galactose mutarotase complexed with D-glucose, D
      fucose, D-quinovose, L-arabinose, or D-xylose. These investigations have revealed
      that there are several distinct binding modes for these sugars, which are
      dependent upon the spatial orientation of the C-4 hydroxyl group. In those sugars
      with the same C-4 hydroxyl group orientation as galactose, their C-1 hydroxyl
      groups are invariably located near Glu-304. For those sugars, which have the same
      C-4 hydroxyl group configuration as glucose, the C-1 hydroxyls are typically
      located near Asp-243. These different binding modes correlate with both the
      observed kinetic parameters and the presence or absence of a hydrogen bond
      between the guanidinium group of Arg-71 and the C-4 hydroxyl group of the sugar
      ligand.

PMID- 12218068
TI  - The discovery of the amino acid threonine: the work of William C. Rose [classical
      article].

PMID- 12218070
TI  - T-cell variant of classical Hodgkin's lymphoma with nodal and cutaneous
      manifestations demonstrated by single-cell polymerase chain reaction.
AB  - The atypical cells of CD30(+) cutaneous lymphoproliferative disorders (CD30CLD)
      are commonly of T-cell origin and frequently have a similar morphology as Hodgkin
      or Reed-Sternberg cells of Hodgkin's lymphoma (HL). HL is one of the tumors
      associated with CD30CLD. Although most studies support a B-cell derivation of the
      tumor cells in HL, recently a few cases of classical HL with T-cell genotype have
      been reported. We report a patient who presented with CD30CLD whose lymph nodes
      showed classical HL of mixed cellularity subtype at presentation. By single-cell
      PCR, the same clonal gene rearrangements of the T cell receptor-beta gene locus
      could be assigned to the CD30(+) and CD15(+) cells of both skin and lymph node.
      In a lymph node biopsy specimen taken in relapse after several courses of
      chemotherapy, the CD30(+) tumor cells were abundant. The T cell-derived tumor
      cells displayed aberrant expression of the Pax-5 gene in all specimens. A common
      clonal origin of both CD30CLD and HL of the lymph node in the patient presented
      here suggests that HL with T-cell genotype exists in association with CD30CLD as
      well as in sporadic cases and may share clonal origin with the skin tumor.

PMID- 12218071
TI  - Functional expression of tumor necrosis factor-related apoptosis-inducing ligand
      in human colonic adenocarcinoma cells.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in various
      transformed cell lines. Therefore, we investigated TRAIL sensitivity, TRAIL
      induced nuclear factor-kappaB (NF-kappaB) activation, and expression of TRAIL in
      human colonic adenocarcinoma cell lines (HT-29, LS180, SK-CO-1). All four TRAIL
      receptors (TRAIL-R1 through TRAIL-R4) are expressed in these cell lines. TRAIL
      sensitivity was assessed by assay of cell viability. Cancer cell viabilities were
      83 +/- 3.1% (HT-29), 90 +/- 4.3% (LS180), and 88 +/- 6.3% (SK-CO-1) at 24 hours
      after the addition of 100 ng/ml TRAIL, indicating that these cell lines were
      relatively resistant to TRAIL. Activation of NF-kappaB was variably influenced by
      TRAIL administration, with no consistent tendency among the cell lines,
      indicating that TRAIL-induced NF-kappaB activation might be cell-type dependent.
      In contrast, TRAIL was expressed in the human colonic adenocarcinoma cell lines
      by Western blotting and RT-PCR. Increased expression of TRAIL on tumor cells was
      observed by flow cytometry after cytokine stimulation (IFN-gamma, TNF-alpha) or
      the addition of chemotherapeutic agents (camptothecin, doxolubicin
      hydrochloride). TRAIL on HT-29 cells was functional and able to induce apoptosis
      in Jurkat cells. Jurkat cell viability was increased by the addition of TRAILR1
      R4-Fc. In the presence of various cytokines or chemotherapeutic agents,
      functional TRAIL is expressed on the surface of tumor cells, and this expressed
      TRAIL might contribute to tumor immune privilege by inducing apoptosis of
      activated human lymphocytes.

PMID- 12218072
TI  - Antibody binding to fas ligand attenuates inflammatory cell infiltration and
      cytokine secretion, leading to reduction of myocardial infarct areas and
      reperfusion injury.
AB  - Fas ligand (FasL) induces apoptotic cell death when bound to Fas antigen. The
      engagement of FasL has anti-inflammatory effects through the prevention of cell
      proliferation and cytokine secretion. However, the role of FasL in myocardial
      ischemia/reperfusion (MI/R) injury is unclear. We examined the expression of FasL
      mRNA in the myocardium of MI/R rats by ligating the left coronary artery for 30
      minutes and allowing reperfusion to occur for 0, 1, 3, and 24 hours. The
      expression of FasL mRNA was enhanced 1 hour after reperfusion, and enhanced
      levels were consistently seen after 24 hours of reperfusion. FasL immunostaining
      was observed on neutrophils, macrophages, T cells, and vascular endothelial
      cells. We then assessed the potential role of FasL in the cell proliferation and
      cytokine production seen in MI/R injury after 24 hours of reperfusion. Rats were
      divided into three groups; Group A, without treatment; Group B, treated with
      nonspecific rabbit IgG; and Group C, treated with anti-FasL antibody. Anti-FasL
      antibody or rabbit IgG were administered intravenously before coronary artery
      occlusion. In Group C, interleukin-1beta and interleukin-2 mRNA levels were
      decreased, and neutrophil and T cell accumulation was attenuated. The infarct
      area determined by triphenyltetrazolium chloride staining was significantly
      smaller in Group C (18 +/- 4%) than in Group A (34 +/- 2%) or Group B (33 +/- 4%)
      (p< 0.0001). However, there was no significant difference in the prevalence of
      terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling
      positive cardiomyocytes among the three groups. These findings suggest that the
      cardioprotective effect of anti-FasL antibody is due to its anti-inflammatory
      action, rather than antiapoptotic action. The Fas/FasL system may be involved in
      the development of MI/R injury.

PMID- 12218073
TI  - Sp3 expression in immune cells: a quantitative study.
AB  - We previously reported the lack of expression of the bifunctional transcription
      factor Sp3 in peripheral blood mononuclear cells from most patients with multiple
      sclerosis (MS) (Grekova et al, 1996). An RT-PCR technique was developed to
      evaluate Sp3 mRNA levels in peripheral blood mononuclear cell subsets. Semi
      quantitative and quantitative competitive RT-PCR assays were used to compare the
      level of Sp3 expression among subjects and among immune cell subsets. The
      competitor DNA fragment contained a deletion from the normal Sp3 cDNA sequence.
      The wild-type Sp3 cDNA and the competitor DNA fragment amplified with equal
      efficiency, and the two PCR products were distinguished by size. These studies
      demonstrated that normal CD4(+) and CD8(+) T cells, B cells, and macrophages
      expressed comparable amounts of Sp3 mRNA. No Sp3 expression could be detected in
      normal natural killer cells nor in any of these cell types from Sp3-negative MS
      patients. We propose that transcription of the Sp3 gene is blocked in immune
      cells from most patients with MS and that this contributes to the development of
      central nervous system inflammation in the disease.

PMID- 12218074
TI  - Anti-p110 autoantibodies identify a subtype of "seronegative" myasthenia gravis
      with prominent oculobulbar involvement.
AB  - Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness
      and pathogenetic autoantibodies directed against the nicotinic acetylcholine
      receptor (seropositive myasthenia gravis; SPMG). Nearly 15% to 20% of MG patients
      do not have these antibodies (seronegative myasthenia gravis; SNMG), but several
      evidence indicate that these patients have circulating pathogenic autoantibodies
      directed against other muscle antigens. Using the TE671 rhabdomyosarcoma cell
      line as an antigen source, we analyzed sera from 63 SNMG and 26 SPMG patients and
      26 healthy blood donors by FACS analysis. We found that 40 of 63 SNMG patients
      and only 1 of 26 SPMG patients had IgG binding to the TE671 cell line. None of
      the sera bound to the unrelated MRC5 cell line. To identify the antigen, we
      analyzed sera immunoreactivity in more detail by immunoprecipitation of
      biotinylated membrane proteins from TE671 cells. When the immunoprecipitated
      proteins were separated by SDS-PAGE electrophoresis and then transferred to
      nitrocellulose membranes, we found that SNMG IgG identify a band corresponding to
      a protein with a molecular weight of 110 kDa (P110), which is not recognized by
      seropositive MG sera. This anti-P110 immunoreactivity is significantly associated
      with a distinct clinical picture characterized by a prominent involvement of
      ocular and bulbar muscles, with frequent respiratory problems (p < 0.005), and is
      recognized by a specific antimuscle specific kinase (MuSK) antiserum. In a recent
      article, the presence of anti-MuSK antibodies was described in SNMG. Our results
      confirm the presence of these antibodies in SNMG and suggest that anti-P110/MuSK
      autoantibodies identify a subtype of SNMG in which the different pathogenesis
      induces the distinct clinical picture.

PMID- 12218075
TI  - Mammaglobin expression in gynecologic malignancies and malignant effusions
      detected by nested reverse transcriptase-polymerase chain reaction.
AB  - The detection of micrometastatic disease remains a challenge for the diagnosis
      and monitoring of malignant disease. RT-PCR for human mammaglobin (hMAM) was
      recently shown to provide a sensitive method for assessing circulating breast
      cancer cells in peripheral blood. This study was aimed at investigating hMAM
      expression in normal and malignant tissue from the female genital tract and the
      prostate as well as in malignant effusions derived from gynecologic malignancies.
      hMAM expression was analyzed with nested RT-PCR in 152 samples of normal (n = 73)
      and malignant epithelial tissues (n = 79) and in 33 specimens of various normal
      mesenchymal tissue types. We found hMAM expression was not restricted to the
      normal mammary gland and breast carcinoma but was also detectable in most
      specimens of benign and malignant epithelial tissue from the ovary (97% versus
      95%), uterus (both 100%), and cervix (91% versus 90%). Notably, hMAM expression
      was also found in benign prostatic hyperplasia (45%) and in prostate cancer
      (55%). A much lower expression rate was found in various normal and benign
      mesenchymal tissues (12%). In keeping with our previous data, hMAM expression was
      absent in all control samples (n = 124) of peripheral blood and bone marrow from
      healthy volunteers and patients with hematologic malignancies. In pleural or
      peritoneal effusions (n = 42) from patients with carcinomas of the breast,
      endometrium, or ovary, hMAM positivity was noticed in the majority of cases
      (74%), whereas only 52% of the specimens were cytologically positive for tumor
      cells. In conclusion, hMAM expression assessed by nested RT-PCR is a sensitive
      molecular marker for detecting micrometastatic tumor spread into pleural
      effusions and ascites from patients with breast cancer and various other
      gynecologic neoplasms.

PMID- 12218076
TI  - Role of the tumor necrosis factor receptor 2 (TNFR2) in cerebral malaria in mice.
AB  - Infection of susceptible mice with Plasmodium berghei Anka leads to a syndrome of
      severe or cerebral malaria. Tumor necrosis factor (TNF) contributes to this
      syndrome, apparently by acting on its receptor 2 (TNFR2) because TNFR1-/- are
      susceptible, whereas TNFR2-/- mice are resistant. In this work, we confirmed the
      essential role of the TNFR2 in cerebral malaria because 6 to 8 days after
      Plasmodium berghei Anka infection, hypothermia, coma, and death were observed in
      +/+ or TNFR1-/-, but never in TNFR2-/-, mice. TNF production, evaluated by the
      serum levels or the mRNA levels in the brain, spleen or lung, was similar in +/+,
      TNFR1-/-, or TNFR2-/- mice. Macrophage or parasitized red blood cell
      sequestration in brain or lung was similar in TNFR1-/- and TNFR2-/- mice.
      Accordingly, up-regulation of CD54 or CD40 in brain or lung was also similar in
      TNFR1-/- or TNFR2-/- mice. Platelet loss, manifested by thrombocytopenia and the
      presence of microparticles in plasma, was similar in TNFR1-/- or TNFR2-/- mice.
      Breakdown of the blood-brain barrier, detected by the diffusion of tracers, was
      attenuated in both TNFR1-/- and TNFR2-/-, compared with +/+, mice. Endothelial
      cells from brain capillaries, examined by transmission electron microscopy, were
      similar in infected TNFR1-/- or TNFR2-/- mice, whereas the basement membrane was
      enlarged in TNFR1-/- mice. Hypothermic mice were also hyperglycemic, and this was
      evident in +/+ and TNFR1-/-, but not in TNFR2-/-, mice. In addition, infected +/+
      and TNFR1-/- mice became insulin resistant, while in contrast TNFR2-/- became
      extremely insulin sensitive. This study supports the possibility that coma and
      death are mediated not by cell sequestration or breakdown of vascular
      permeability, similar in TNFR1-/- or TNFR2-/- mice, but by metabolic disturbances
      selectively mediated by the TNFR2.

PMID- 12218077
TI  - Variable nuclear localization of alpha-catenin in colorectal carcinoma.
AB  - The E-cadherin/catenin complex plays a major role in epithelial cell-cell
      adhesion. Both beta-catenin and gamma-catenin bind directly to the cytoplasmic
      domain of E-cadherin whereas alpha-catenin links the bound beta-catenin or gamma
      catenin to the actin microfilament network of the cellular cytoskeleton.
      Significant changes in the expression and/or structure of members of the complex
      can occur in neoplasia. Several studies have reported on the nuclear localization
      of beta- and gamma-catenin and on their role in influencing the transcriptional
      activity of several proto-oncogenes. The cellular localization of alpha-catenin
      has not been studied in detail. The aim of this study was to investigate the
      cellular localization of alpha-catenin in colorectal carcinoma both in vitro and
      in vivo and to assess whether it might be relevant to tumor behavior. The
      expression of alpha-catenin was examined in a panel of colorectal carcinoma cell
      lines (SW480, SW620, HCT116, HT29, and Caco-2) using a combination of
      immunohistochemistry, confocal fluorescence microscopy, and Western blotting. The
      expression of alpha-catenin was also studied by immunohistochemistry in 15
      sporadic colorectal adenomas, 30 sporadic colorectal adenocarcinomas, and their
      13 lymph node metastases. From familial adenomatous polyposis patients, 20
      adenomas and 5 adenocarcinomas were studied. Nuclear localization of alpha
      catenin was detected in the colorectal carcinoma cell lines when the cells were
      dispersed rather than confluent. alpha-catenin was not detected in the nuclei in
      any of the sporadic or familial adenomas. However, it was detected in one
      sporadic and one familial adenocarcinoma but not in any of the lymph node
      deposits. alpha-catenin can localize to the nuclei of colorectal tumor cells, and
      this may be related to lack of perception of connection to adjacent cells.

PMID- 12218078
TI  - Establishment and characterization of a novel human desmoplastic small round cell
      tumor cell line, JN-DSRCT-1.
AB  - The exact nature of the desmoplastic small round cell tumor (DSRCT) remains
      controversial. More detailed analyses might be facilitated by the establishment
      of permanent DSRCT cell lines. To date, however, no human DSRCT cell line has
      been reported. In this study, we report the establishment of a new human cell
      line, JN-DSRCT-1, from the pleural effusion of a 7-year-old boy with pulmonary
      metastasis from a typical intra-abdominal DSRCT. JN-DSRCT-1 cells were small
      round or spindle shaped with oval nuclei and have been maintained continuously in
      vitro for over 190 passages during more than 40 months. Histologic features of
      the heterotransplanted tumors in severe combined immunodeficiency mouse were
      essentially the same as those of the original DSRCT, revealing nests or clusters
      of small round cells embedded in an abundant desmoplastic stroma. Both in vitro
      and in vivo, the cells exhibited immunopositive reactions for vimentin, desmin,
      cytokeratins (AE1/AE3 and CAM 5.2), epithelial membrane antigen, neuron-specific
      antigen, and CD57 (Leu-7). JN-DSRCT-1 cells exhibited a pathognomonic
      t(11;22)(p13;q12) translocation by cytogenetic analysis. In addition, RT-PCR and
      sequencing analysis revealed a chimeric transcriptional message of the Ewing's
      sarcoma gene exon 10 fused to the Wilms' tumor gene exon 8. To our knowledge,
      this is the first permanent human DSRCT cell line. The JN-DSRCT-1 cell line,
      which exhibits the unique morphologic and genetic characteristics of DSRCT, will
      be extremely useful for a variety of important studies such as the pathogenic
      mechanism, biologic behavior, and therapeutic model of human DSRCT.

PMID- 12218080
TI  - Lack of expression of the Epstein-Barr Virus (EBV) gene products, EBERs, EBNA1,
      LMP1, and LMP2A, in breast cancer cells.
AB  - Epstein-Barr virus (EBV), a gamma herpesvirus, has been associated with a variety
      of human malignancies such as Burkitt's lymphoma, Hodgkin's lymphoma, NPC, and
      gastric cancer. A controversy regarding the association of EBV with breast
      cancers has recently been reported in the literature. These reports have mainly
      used the DNA detection techniques of polymerase chain reaction and Southern blot
      hybridization, with the inherent lacunae associated with these techniques for
      signal localization. Our group has studied EBV association with breast cancer by
      using in situ hybridization for detecting nonpolyadenylated EBV RNA (EBERs),
      along with using protein localization technique of immunohistochemistry, studying
      the EBV nuclear antigen 1 (EBNA1) and the latent membrane proteins (LMP1 and
      LMP2A). This is the first article analyzing the expression of LMP2A in breast
      cancer cells. In all of our 43 female breast cancer cases under study, we failed
      to detect expression of any of the EBV viral gene products tested.

PMID- 12218079
TI  - Peripheral blood fibrocytes from burn patients: identification and quantification
      of fibrocytes in adherent cells cultured from peripheral blood mononuclear cells.
AB  - Peripheral blood fibrocytes are a newly identified leukocyte subpopulation that
      displays fibroblast-like properties. These blood-borne cells can rapidly enter
      the site of injury at the same time as circulating inflammatory cells. We
      hypothesize that circulating fibrocytes represent an important source of
      fibroblasts for healing of extensive burn wounds where it may be difficult for
      fibroblasts to migrate from the edges of uninjured tissue. In this study we
      identified and quantified fibrocytes among the adherent cells cultured from human
      peripheral blood mononuclear cells (PBMC) obtained from 18 burn patients and 12
      normal individuals, based on their ability to express type I collagen. Our
      results showed that adherent cells cultured from PBMC of burn patients
      differentiated to fibrocytes more efficiently than did those from normal
      individuals. The percentage of type I collagen-positive fibrocytes was
      significantly higher for patients than for controls (89.7 +/- 7.9% versus 69.9 +/
      14.7%, p < 0.001). This percentage was consistently higher for patients with a
      >/=30% total body surface area burn until 1 year, with the highest percentage
      appearing within 3 weeks of injury. A positive correlation was found between the
      levels of serum transforming growth factor-beta1 (TGF-beta1) and the percentage
      of fibrocytes developing in the cultures of PBMC derived from these patients. We
      also demonstrated that fibrocytes were derived from CD14(+) cells but not CD14(-)
      cells. Conditioned medium from CD14(-) cells was, however, required for fibrocyte
      differentiation, whereas direct contact between CD14(-) and CD14(+) cells was not
      necessary. Treatment of the cell cultures with TGF-beta1 enhanced the development
      of collagen-positive cells, whereas the inclusion of neutralizing anti-TGF-beta1
      antibodies in the CD14(-) conditioned medium suppressed fibrocyte
      differentiation. These data suggest that the development of fibrocytes is up
      regulated systemically in burn patients. Increased TGF-beta in serum stimulates
      the differentiation of the CD14(+) cell population in PBMC into collagen
      producing cells that may be important in wound healing and scarring.

PMID- 12218081
TI  - Preferential loss of Fhit expression in signet-ring cell and Krukenberg subtypes
      of gastric cancer.
AB  - Gastric cancer of youth is predominantly a disease of women, usually of the
      signet-ring cell subtype, with a predilection for metastasizing to the ovaries.
      The metastatic ovarian tumor is named a Krukenberg tumor. However, the
      characteristic genetic alterations between the primary gastric cancer and its
      metastatic ovarian tumor have not been studied. We used laser capture
      microdissection to procure tissues from 7 patients with gastric cancer who had
      ovarian metastases (Krukenberg tumor) and tissues from 14 patients with gastric
      cancer without ovarian metastases. Loss of heterozygosity (LOH) analysis was
      performed by use of 16 polymorphic markers, which are mapped to the FHIT, APC,
      p16, BRCA2, E-cadherin, p53, BRCA1, and DPC4 loci. Immunohistochemical staining
      with anti-Fhit antibody was performed in 7 Krukenberg tumors and 92 gastric
      cancers without ovarian metastases. LOH at the FHIT locus was observed in six
      (85.7%) of the seven Krukenberg tumors. In contrast, the gastric cancers without
      ovarian metastases showed a lower frequency (28.6%, 4/14) of LOH at the FHIT
      locus (p < 0.05, odds ratio = 1/15). Anti-Fhit antibody showed that expression of
      Fhit was lost in each of the 7 (100%) Krukenberg tumors but in only 41 (44.6%) of
      the 92 patients who had gastric cancer without ovarian metastases (p < 0.05; odds
      ratio = 1/18.614). Further analysis showed that loss of Fhit expression is highly
      associated with signet-ring cell type gastric cancer (p < 0.0001, odds ratio =
      62.5) but is not correlated with prognosis. Alteration of the FHIT gene is a
      characteristic of signet-ring cell type gastric cancer and Krukenberg tumor.

PMID- 12218082
TI  - Glomerular endothelium exhibits enhanced expression of costimulatory adhesion
      molecules, CD80 and CD86, by warm ischemia/reperfusion injury in rats.
AB  - Recent studies suggested that the vascular endothelial cells function as a
      resident antigen-presenting cell (APC) in certain situations such as organ
      transplantation, and the ischemia/reperfusion injury, an inevitable event in
      organ transplantation, leads to an enhanced biosynthesis of cell adhesion
      molecules. We have demonstrated that the hepatic sinusoidal endothelial cells
      have potential ability as APCs by expressing the costimulatory adhesion molecule
      proteins, CD80 (B7-1) and CD86 (B7-2), of which expression was enhanced by warm
      ischemia/reperfusion of the rat liver. In this study, we assessed the
      localization of CD80, CD86, and intercellular adhesion molecule 1 in the rat
      kidneys and the influence of warm ischemia/reperfusion with or without a
      hypercreatinemic condition on the expression of these adhesion molecules in the
      renal tissues. Wistar male rats weighing 150 to 230 g were divided into group A,
      receiving a sham-operation (control), group B, receiving 1-hour clamping of the
      left renal pedicle (temporary ischemia), and group C, receiving right nephrectomy
      and 1-hour clamping of the left renal pedicle (temporary ischemia with
      hypercreatinemia). The left kidneys were submitted to immunohistochemical and
      molecular analyses sequentially for the period of 14 days. We found that CD80,
      CD86, and intercellular adhesion molecule 1 proteins localized on the glomerular
      and peritubular endothelium and were up-regulated after ischemia/reperfusion. The
      up-regulation of these three proteins was enhanced by the hypercreatinemic
      condition. The relative mRNA levels analyzed by real-time reverse transcription
      polymerase chain reaction showed that CD80 and CD86 expressions were
      constitutively observed and significantly increased for 14 days after the warm
      ischemia reperfusion with a peak level at Day 3 (6.7- and 20.8-fold increase for
      CD80 and CD86, respectively). Our results suggested that the glomerular
      endothelial cells will play a pivotal role as a APC by expressing CD80 and CD86
      in the induction of renal tissue injury associated with the ischemia/reperfusion
      at renal transplantation surgery, as well as the peritubular endothelium.

PMID- 12218083
TI  - Effects of anti-alpha1 integrin subunit antibody on anti-Thy-1
      glomerulonephritis.
AB  - alpha1beta1 integrin is a potential collagen-binding extracellular matrix
      receptor that mediates collagen-dependent cell adhesion, proliferation,
      migration, and collagen matrix assembly and thereby may participate in the wound
      healing and pathologic scarring observed in some damaged organs. To clarify the
      role of alpha1beta1 integrin predominantly expressed on the mesangial cell (MC)
      surface in nephritic glomeruli, we investigated the involvement of MC-alpha1beta1
      integrin in rat anti-Thy-1 glomerulonephritis (GN) by administering function
      blocking monoclonal mouse anti-rat alpha1 integrin subunit antibody (anti-alpha1
      Ab). Assay of collagen types I and IV mixed gel contraction, an in vitro model of
      pathologic collagen matrix remodeling, with function-blocking anti-alpha1 Ab and
      anti-beta1 Ab, revealed that collagen I and IV matrix reorganization is mediated
      by MC-alpha1beta1 integrin. In addition, conditioned medium from isolated Day 3
      anti-Thy-1 nephritic glomeruli showed increased activity of MC-alpha1beta1
      integrin-induced mixed collagen gel contraction as compared with that from
      isolated normal rat glomeruli. Treatment of Day 3 conditioned medium with anti
      platelet-derived growth factor-BB antibody significantly inhibited conditioned
      media-induced gel contraction, whereas treatment with anti-transforming growth
      factor-beta antibody did not have a significant effect. Rats that received anti
      alpha1 Ab from the left renal artery 3 days after anti-Thy-1 GN induction showed
      significant decreases of glomerular hypercellularity and mesangial matrix
      accumulation, including collagen I and IV in the left kidney, compared with those
      rats in which the left kidney received control mouse IgG1. These results suggest
      that MC-alpha1beta1 integrin is an important extracellular matrix receptor
      mediating mesangial remodeling characterized by MC proliferation and mesangial
      matrix reorganization in anti-Thy-1 GN. Platelet-derived growth factor-BB may be
      involved in early collagen matrix reorganization leading to pathologic mesangial
      remodeling in this GN model.

PMID- 12218084
TI  - Calmodulin overexpression causes Ca(2+)-dependent apoptosis of pancreatic beta
      cells, which can be prevented by inhibition of nitric oxide synthase.
AB  - We investigated the mechanism of beta-cell loss in transgenic mice with elevated
      levels of beta cell calmodulin. The transgenic mice experienced a sudden rise in
      blood glucose levels between 21 and 28 days of age. This change was associated
      with development of severe hypoinsulinemia and loss of beta cells from the
      islets. Ultrastructural analysis revealed that compromised granule formation and
      apoptotic changes in the transgenic beta cells preceded the onset of
      hyperglycemia. Intraperitoneal injection of tolbutamide, an antidiabetic
      sulfonylurea, decreased blood glucose levels but increased the number of
      apoptotic beta cells. Finally, injection of transgenic mice with N(omega)-nitro-L
      arginine methyl ester, which inhibits nitric oxide synthase activity, prevented
      hyperglycemia and lessened the changes in number and size of beta cells. Because
      immunofluorescent staining revealed preferential distribution of neural nitric
      oxide synthase in pancreatic beta cells, we speculate that overexpression of
      calmodulin sensitizes the beta cells to Ca(2+)-dependent activation of neural
      nitric oxide synthase, which mediates apoptosis.

PMID- 12218085
TI  - Gastrin significantly modifies the migratory abilities of experimental glioma
      cells.
AB  - Malignant astrocytic tumors are characterized by the pronounced and diffuse
      migration of tumor astrocytes into the brain parenchyma. The present study shows
      that gastrin is a brain neuropeptide that is able to significantly modulate
      astrocytic tumor migration at both invasion and motility levels. In the matter of
      invasion, gastrin severely reduces the in vitro invasive abilities of C6 rat
      glioma, 9L rat gliosarcoma, and U373 human glioma cells in a collagen matrix. In
      vitro, gastrin also markedly modifies the motility features in both C6 and U373
      cells, at least partly through a decrease in the expression of the RhoA small
      GTPase, and so brings about some dramatic modifications to the organization in
      the actin cytoskeleton. The in vitro preincubation of C6 tumor cells with gastrin
      significantly increases the life spans of rats stereotactically implanted with
      these cells as compared with the survival periods of rats implanted with gastrin
      untreated C6 cells. As suggested by our in vitro experiments, these effects,
      observed in vivo cannot relate to only the gastrin-induced decrease in tumor
      astrocyte migratory abilities. Indeed, gastrin also induces immunomodulatory
      effects, because we observed a marked gastrin-induced recruitment of lymphocytes
      into C6 gliomas and 9L gliosarcomas. These data all suggest that gastrin can act
      as an endogenous modulator of glioma progression.

PMID- 12218086
TI  - Urinary excretion of lipoxin A(4) and related compounds: development of new
      extraction techniques for lipoxins.
AB  - LX are tetraene-containing eicosanoids generated by lipoxygenase (LO)
      transformation of arachidonic acid (Serhan and Romano, 1995). LX possess potent
      anti-inflammatory activity in vivo, and temporal biosynthesis of LX, concurrent
      with spontaneous resolution, has been observed during exudate formation (Levy et
      al, 2001). Limited results are currently available on the involvement of LX in
      clinical settings. Recently, a rabbit anti-LXA(4) antiserum has been raised to
      produce an enzyme-linked immunosorbent assay (ELISA) kit for LXA(4) (Levy et al,
      1993). Although specific and accurate with isolated cells, this kit has not been
      tested with complex biological matrix such as urine. Initial attempts to
      determine urinary excretion of LXA(4) using the LXA(4) ELISA kit were
      unsuccessful because of high unspecific absorbance readings. In this report, we
      show that the LXA(4) extraction procedure indicated in the ELISA kit is
      inadequate for urinary measurements of immunoreactive (i)LXA(4). We present the
      development of a new extraction technique, more selective for LX, that abolishes
      background contamination and minimizes the unspecific readings. Using this
      method, we show for the first time that urine from healthy subjects contain
      (i)LXA(4) material and identify a urinary tetraene with the physical properties
      of a LXA(4) metabolite. Although reliable methods have been previously
      established to quantitate LXA(4) from whole blood (Brezinski et al, 1992), the
      present extraction technique, which optimizes for LXA(4) recovery from human
      urine, represents a substantial achievement for LX investigation and may open a
      new avenue of clinical studies on LXA(4).

PMID- 12218087
TI  - A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary
      tumors.

PMID- 12218088
TI  - Highly stable fluorescent nanocrystals as a novel class of labels for
      immunohistochemical analysis of paraffin-embedded tissue sections.

PMID- 12218089
TI  - Cutting edge: Fyn is essential for tyrosine phosphorylation of Csk-binding
      protein/phosphoprotein associated with glycolipid-enriched microdomains in lipid
      rafts in resting T cells.
AB  - In resting T cells, Csk is constitutively localized in lipid rafts by virtue of
      interaction with a phosphorylated adaptor protein, Csk-binding protein
      (Cbp)/phosphoprotein associated with glycolipid-enriched microdomains, and sets
      an activation threshold in TCR signaling. In this study, we examined a kinase
      responsible for Cbp phosphorylation in T cell membrane rafts. By analyzing T
      cells from Fyn-/- mice, we clearly demonstrated that Fyn, but not Lck, has its
      kinase activity in membrane rafts, and plays a critical role in Cbp
      phosphorylation, Cbp-Csk interaction, and Csk kinase activity. Naive
      CD44(low)CD62 ligand(high) T cells were substantially reduced in Fyn-/- mice,
      presumably due to the inhibition of Cbp phosphorylation. Thus, Fyn mediates Cbp
      Csk interaction and recruits Csk to rafts by phosphorylating Cbp. Csk recruited
      to rafts would then be activated and inhibit the kinase activity of Lck to keep
      resting T cells in a quiescent state. Our results elucidate a negative regulatory
      role for Fyn in proximal TCR signaling in lipid rafts.

PMID- 12218090
TI  - Cutting edge: susceptibility to psoriatic arthritis: influence of activating
      killer Ig-like receptor genes in the absence of specific HLA-C alleles.
AB  - NK cell activity is partially controlled through interactions between killer Ig
      like receptors (KIR) on NK cells and their respective HLA class I ligands.
      Independent segregation of HLA and KIR genes, along with KIR specificity for
      particular HLA allotypes, raises the possibility that any given individual may
      express KIR molecules for which no ligand is present. Inhibitory receptor genes
      KIR2DL2/3 and KIR2DL1 were present in nearly all subjects sampled in this study,
      whereas their respective activating homologs, KIR2DS2 and KIR2DS1, are each
      present in about half of the subjects. In this work we report that subjects with
      activating KIR2DS1 and/or KIR2DS2 genes are susceptible to developing psoriatic
      arthritis, but only when HLA ligands for their homologous inhibitory receptors,
      KIR2DL1 and KIR2DL2/3, are missing. Absence of ligands for inhibitory KIRs could
      potentially lower the threshold for NK (and/or T) cell activation mediated
      through activating receptors, thereby contributing to pathogenesis of psoriatic
      arthritis.

PMID- 12218091
TI  - Cutting edge: myeloid differentiation factor 88 deficiency improves resistance
      against sepsis caused by polymicrobial infection.
AB  - Toll-like receptors (TLRs) are important for the activation of innate immune
      cells upon encounter of microbial pathogens. The present study investigated the
      potential roles of TLR2, TLR4, and the signaling protein myeloid differentiation
      factor 88 (MyD88) in polymicrobial septic peritonitis. Whereas both TLR2 and TLR4
      were dispensable for host defense against septic peritonitis, MyD88-deficient
      mice were protected in this infection model. Recruitment of neutrophils to the
      septic focus and bacterial clearance were normal in MyD88-deficient mice. In
      contrast, the systemic inflammatory response was strongly attenuated in the
      absence of MyD88. Surprisingly, MyD88 deficiency did not alter cytokine and
      chemokine production in spleen, but markedly reduced the inflammatory response in
      liver and lung. Production of monocyte chemoattractant protein-1 and macrophage
      inflammatory protein-1alpha was entirely independent of MyD88. These results
      imply a central role of MyD88 for the systemic immune pathology of polymicrobial
      sepsis and show that cytokine production in spleen and induction of certain
      chemokines are MyD88 independent.

PMID- 12218092
TI  - Cutting edge: profound defect in T cell responses in TNF receptor-associated
      factor 2 dominant negative mice.
AB  - TNFR-associated factor 2 (TRAF2) is an adapter protein that links several members
      of the TNFR family to downstream signaling pathways. Mice expressing a dominant
      negative form of TRAF2 in their lymphoid cells (TRAF2.DN mice) have a profound
      defect in T cell responses to allogeneic APC. In contrast, APC from wild-type or
      TRAF2.DN mice show an equivalent level of stimulation in a MLR. Ab production and
      class switch are unimpaired in TRAF2.DN mice. Thus, defects in the TRAF.DN mice
      appear to be limited to T cells. TRAF2.DN mice demonstrate an impaired T cell
      response to influenza virus, including decreased secondary expansion of IFN-gamma
      secreting T cells as well as a decrease in CTL activity. CD4 T cell production of
      IL-2 was also dramatically impaired in TRAF2.DN mice. These studies suggest an
      essential role of TRAF2-linked receptors in secondary CD4 and CD8 T cell
      responses and have important implications for transplantation.

PMID- 12218093
TI  - Cutting edge: the relative distribution of T cells responding to chemically
      dominant or minor epitopes of lysozyme is not affected by CD40-CD40 ligand and B7
      CD28-CTLA-4 costimulatory pathways.
AB  - We examined the frequencies and specificities of the CD4+ T cell responses to the
      protein hen egg white lysozyme in mice deficient in the CD40-CD40 ligand or B7
      CD28 costimulatory pathways. The frequency of T cells was decreased by between 3-
      and 4-fold in CD40-/- mice, and 12-fold in B7-1/B7-2-/- mice, but surprisingly,
      the relative distribution of T cells responding to peptides that were presented
      at levels that differed by >250-fold was similar. We also examined the CD4
      response after blocking the regulatory molecule CTLA-4 during immunization. We
      observed no difference in either the frequency or specificity of the CD4+ T cell
      response if CTLA-4 was blocking during priming. Thus, the T cell response was
      generated toward the constellation of chemically dominant and subdominant
      epitopes as a whole, and did not discriminate among them based on their relative
      abundance.

PMID- 12218094
TI  - Cutting edge: quantitative imaging of raft accumulation in the immunological
      synapse.
AB  - Although the accumulation of lipid rafts at the immunological synapse is now well
      accepted, the degree of the accumulation, the localization within the fine
      structure of the immunological synapse, and the region from which lipid rafts are
      recruited have not been defined. In this work we show that lipid rafts
      preferentially accumulate in the central zone of the immunological synapse, the
      central supramolecular activation complex (C-SMAC). However, quantitative
      analyses indicate that the level of recruitment of lipid rafts to the C-SMAC is
      relatively small and suggests that rearrangement of lipid rafts from the
      peripheral zone of the synapse into the C-SMAC can account for this accumulation.
      We also assessed the effects of CD28 deficiency on lipid raft recruitment to the
      immunological synapse. The accumulation of lipid occurred independently of the
      CD28/B7 system and was not measurably altered by CD28.

PMID- 12218096
TI  - Cutting edge: Salmonella AvrA effector inhibits the key proinflammatory, anti
      apoptotic NF-kappa B pathway.
AB  - Secreted prokaryotic effector proteins have evolved to modulate the cellular
      functions of specific eukaryotic hosts. Generally, these proteins are considered
      virulence factors that facilitate parasitism. However, in certain plant and
      insect eukaryotic/prokaryotic relationships, effector proteins are involved in
      the establishment of commensal or symbiotic interactions. In this study, we
      report that the AvrA protein from Salmonella typhimurium, a common enteropathogen
      of humans, is an effector molecule that inhibits activation of the key
      proinflammatory NF-kappaB transcription factor and augments apoptosis in human
      epithelial cells. This activity is similar but mechanistically distinct from that
      described for YopJ, an AvrA homolog expressed by the bacterial pathogen Yersinia.
      We suggest that AvrA may limit virulence in vertebrates in a manner analogous to
      avirulence factors in plants, and as such, is the first bacterial effector from a
      mammalian pathogen that has been ascribed such a function.

PMID- 12218095
TI  - Cutting edge: thymocyte-independent and thymocyte-dependent phases of epithelial
      patterning in the fetal thymus.
AB  - Thymic epithelial cells (TECs) in adult mice have been classified into distinct
      subsets based on keratin expression profiles. To explore the emergence of TEC
      subsets during ontogeny, we analyzed keratin 8 and keratin 5 expression at
      several stages of fetal development in normal C57BL/6J mice. In addition, thymic
      epithelial development and compartmentalization were explored in recombination
      activating gene 2/common cytokine receptor gamma-chain-deficient and Ikaros-null
      mice that sustain early and profound blocks in thymocyte differentiation. The
      results demonstrate that initial patterning of the thymic epithelial compartment
      as defined by differential keratin expression does not depend on inductive
      signals from hematopoietic cells. However, thymocyte-derived signals are required
      during late fetal stages for continued development and maintenance of TEC subsets
      in the neonate and adult.

PMID- 12218097
TI  - Mitogen-activated protein kinase/extracellular signal-regulated kinase signaling
      in activated T cells abrogates TRAIL-induced apoptosis upstream of the
      mitochondrial amplification loop and caspase-8.
AB  - Fas ligand and TNF-related apoptosis-inducing ligand (TRAIL) induce apoptosis in
      many different cell types. Jurkat T cells die rapidly by apoptosis after
      treatment with either ligand. We have previously shown that mitogen-activated
      protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) can act as a
      negative regulator of apoptosis mediated by the Fas receptor. In this study we
      examined whether MAPK/ERK can also act as a negative regulator of apoptosis
      induced by TRAIL. Activated Jurkat T cells were efficiently protected from TRAIL
      induced apoptosis. The protection was shown to be MAPK/ERK dependent and
      independent of protein synthesis. MAPK/ERK suppressed TRAIL-induced apoptosis
      upstream of the mitochondrial amplification loop because mitochondrial
      depolarization and release of cytochrome c were inhibited. Furthermore, caspase-8
      mediated relocalization and activation of Bid, a proapoptotic member of the Bcl
      family, was also inhibited by the MAPK/ERK signaling. The protection occurred at
      the level of the apoptotic initiator caspase-8, as the cleavage of caspase-8 was
      inhibited but the assembly of the death-inducing signaling complex was
      unaffected. Both TRAIL and Fas ligand have been suggested to regulate the clonal
      size and persistence of different T cell populations. Our previous results
      indicate that MAPK/ERK protects recently activated T cells from Fas receptor
      mediated apoptosis during the initial phase of an immune response before the
      activation-induced cell death takes place. The results of this study show clearly
      that MAPK/ERK also participates in the inhibition of TRAIL-induced apoptosis
      after T cell activation.

PMID- 12218098
TI  - Severe immunodeficiency has opposite effects on neuronal survival in glutamate
      susceptible and -resistant mice: adverse effect of B cells.
AB  - The resistance of rats or mice to glutamate-induced toxicity depends on their
      ability to spontaneously manifest a T cell-dependent response to the insult.
      Survival of retinal ganglion cells (RGCs) exposed to glutamate in BALB/c SCID
      mice (a strain relatively resistant to glutamate toxicity) was significantly
      worse than in the wild type. In the susceptible C57BL/6J mouse strain, however,
      significantly more RGCs survived among SCID mutants than in the matched wild
      type. RGC survival in the SCID mutants of the two strains was similar. These
      results suggest 1) that immunodeficiency might be an advantage in strains
      incapable of spontaneously manifesting protective T cell-dependent immunity and
      2) that B cells might be destructive in such cases. After exposure of RGCs to
      toxic glutamate concentrations in three variants of B cell-deficient C57BL/6J
      mice, namely muMT(-/-) (B cell knockout mice) and Ii(-/-) mice reconstituted with
      transgenically expressed low levels of Ii p31 isoforms (p31 mice) or Ii p41
      isoforms (p41 mice), significantly more RGCs survived in these mice than in the
      wild type. The improved survival was diminished by replenishment of the B cell
      deficient mice with B cells derived from the wild type. It thus seems that B
      cells have an adverse effect on neuronal recovery after injury, at least in a
      strain that is unable to spontaneously manifest a T cell-dependent protective
      mechanism. These findings have clear implications for the design of immune-based
      therapies for CNS injury.

PMID- 12218100
TI  - Endogenous granulocyte-macrophage colony-stimulating factor overexpression in
      vivo results in the long-term recruitment of a distinct dendritic cell population
      with enhanced immunostimulatory function.
AB  - GM-CSF is critical for dendritic cell (DC) survival and differentiation in vitro.
      To study its effect on DC development and function in vivo, we used a gene
      transfer vector to transiently overexpress GM-CSF in mice. We found that up to
      24% of splenocytes became CD11c+ and the number of DC increased up to 260-fold to
      3 x 10(8) cells. DC numbers remained substantially elevated even 75 days after
      treatment. The DC population was either CD8alpha+CD4- or CD8alpha-CD4- but not
      CD8alpha+CD4+ or CD8alpha-CD4+. This differs substantially from subsets recruited
      in normal or Flt3 ligand-treated mice or using GM-CSF protein injections. GM-CSF
      recruited DC secreted extremely high levels of TNF-alpha compared with minimal
      amounts in DC from normal or Flt3 ligand-treated mice. Recruited DC also produced
      elevated levels of IL-6 but almost no IFN-gamma. GM-CSF DC had robust immune
      function compared with controls. They had an increased rate of Ag capture and
      caused greater allogeneic and Ag-specific T cell stimulation. Furthermore, GM-CSF
      recruited DC increased NK cell lytic activity after coculture. The enhanced T
      cell and NK cell immunostimulation by GM-CSF DC was in part dependent on their
      secretion of TNF-alpha. Our findings show that GM-CSF can have an important role
      in DC development and recruitment in vivo and has potential application to
      immunotherapy in recruiting massive numbers of DC with enhanced ability to
      activate effector cells.

PMID- 12218099
TI  - Enforced expression of Runx2 perturbs T cell development at a stage coincident
      with beta-selection.
AB  - The development of T cells in the thymus is regulated by a series of stage
      specific transcription factors. Deregulated expression of these factors can lead
      to alterations in thymocyte development with the production of aberrant cell
      subsets and predispose to tumor formation. The three genes of the Runx family are
      multilineage regulators of differentiation that have been reported to be
      expressed in the T cell lineage. However, their roles in thymocyte development
      and T cell function are largely unknown. While the Runx2/Cbfa1/AML3/Pebp2alphaa
      gene plays a primary role in osteogenesis and regulates a number of key bone
      regulatory genes, we show here that Runx2 is also expressed during the earliest
      phase of thymic development, in the double-negative subset. Furthermore, enforced
      expression of Runx2 in transgenic mice under the CD2 promoter was found to affect
      T cell development at a stage coincident with beta-selection, resulting in an
      expansion of double-negative CD4 and CD8 immature single-positive cells. Unlike
      wild-type controls this preselection population (CD4-CD8+heat-stable Ag+TCR-) is
      in a nonproliferative state, but appears to be primed for further transformation
      events. Overall the data suggest that Runx2 accelerates development to the CD8
      immature single-positive stage, but retards subsequent differentiation to the
      double-positive stage. Thus, Runx2 joins a small group of transcription factors
      that can interfere with early T cell development, cause an expansion of a
      specific subset, and predispose to lymphoma.

PMID- 12218101
TI  - Colocalization of the B cell receptor and CD20 followed by activation-dependent
      dissociation in distinct lipid rafts.
AB  - The B cell Ag receptor (BCR) and CD20, a putative calcium channel, inducibly
      associate with cholesterol-dependent membrane microdomains known as lipid rafts.
      A functional association between the BCR and CD20 is suggested by the effects of
      CD20-specific mAbs, which can modulate cell cycle transitions elicited by BCR
      signaling. Using immunofluorescence microscopy we show here that the BCR and CD20
      colocalize after receptor ligation and then rapidly dissociate at the cell
      surface before endocytosis of the BCR. After separation, surface BCR and CD20
      were detected in distinct lipid rafts isolated as low density, detergent
      resistant membrane fragments. Pretreatment with methyl-beta-cyclodextrin, which
      we have previously shown to enhance receptor-mediated calcium mobilization, did
      not prevent colocalization of the BCR and CD20, but slowed their dissociation.
      The data demonstrate rapid dynamics of the BCR in relation to CD20 at the cell
      surface. Activation-dependent dissociation of the BCR from CD20 occurs before
      receptor endocytosis and appears to require in part the integrity of lipid rafts.

PMID- 12218102
TI  - Surfactant protein D reduces alveolar macrophage apoptosis in vivo.
AB  - Surfactant protein D (SP-D) is a molecule of the innate immune system that
      recognizes the patterns of surface carbohydrate on pathogens and targets them for
      phagocytosis and killing. SP-D-deficient mice show an increased number of
      macrophages in the alveolar space, excess surfactant phospholipid, overproduction
      of reactive oxygen species, and the development of emphysema. We report here that
      SP-D-deficient mice have a 5- to 10-fold increase in the number of apoptotic and
      necrotic alveolar macrophages, as defined by annexin V and propidium iodine
      staining, respectively. Intrapulmonary administration of a truncated 60-kDa
      fragment of human recombinant SP-D reduces the number of apoptotic and necrotic
      alveolar macrophages and partially corrects the lipid accumulation in SP-D
      deficient mice. The same SP-D fragment binds preferentially to apoptotic and
      necrotic alveolar macrophages in vitro, suggesting that SP-D contributes to
      immune homeostasis in the lung by recognizing and promoting removal of necrotic
      and apoptotic cells.

PMID- 12218104
TI  - Superantigen enhancement of specific immunity: antibody production and signaling
      pathways.
AB  - Superantigens are microbial proteins that induce massive activation,
      proliferation, and cytokine production by CD4+ T cells via specific Vbeta
      elements on the TCR. In this study we examine superantigen enhancement of Ag
      specific CD4+ T cell activity for humoral B cell responses to T-dependent Ags BSA
      and HIV gp120 envelope, type I T-independent Ag LPS, and type II T-independent Ag
      pneumococcal polysaccharides. Injection of BSA followed by a combination of
      superantigens staphylococcal enterotoxin A and staphylococcal enterotoxin B (SEB)
      7 days later enhanced the anti-BSA Ab response in mice approximately 4-fold as
      compared with mice given BSA alone. The anti-gp120 response was enhanced
      approximately 3-fold by superantigens. The type II T-independent Ag pneumococcal
      polysaccharide response was enhanced approximately 2.3-fold by superantigens,
      whereas no effect was observed on the response to the type I T-independent Ag
      LPS. The superantigen effect was completely blocked by the CD4+ T cell inhibitory
      cytokine IL-10. SEB-stimulated human CD4+ T cells were examined to determine the
      role of the mitogen-activated protein (MAP) kinase signal transduction pathway in
      superantigen activation of T cells. Inhibitors of the mitogen pathway of MAP
      kinase blocked SEB-induced proliferation and IFN-gamma production, while an
      inhibitor of the p38 stress pathway had no effect. Consistent with this, SEB
      activated extracellular signal-regulated kinase/MAP kinase as well as MAP kinase
      interacting kinase, a kinase that phosphorylates eIF4E, which is an important
      component of the eukaryotic protein synthesis initiation complex. Both kinases
      were inhibited by IL-10. Thus, superantigens enhance humoral immunity via Ag
      specific CD4+ T cells involving the stress-independent pathway of MAP kinase.

PMID- 12218103
TI  - Th2 activities induced during virgin T cell priming in the absence of IL-4, IL
      13, and B cells.
AB  - Virgin T cells being primed to Th2-inducing or Th1-inducing Ags, respectively,
      start to synthesize IL-4 or IFN-gamma as they begin to proliferate. Parallel
      respective induction of B cells to produce gamma1 or gamma2a switch transcripts
      provides additional evidence of early divergent Th activity. This report concerns
      the roles of IL-4, IL-13, and B cells in these early events in vivo. Th2
      responses were induced in lymph nodes against hapten-protein given s.c. with
      killed Bordetella pertussis adjuvant. In T cell proliferation in wild-type mice,
      IL-4 message up-regulation and gamma1 and epsilon switch transcript production
      were underway 48-72 h after immunization. The absence of IL-4, IL-13, or B cells
      did not alter the early T cell proliferative response. The gamma1 and epsilon
      switch transcript production was still induced in the absence of IL-4, IL-13, or
      both, but at a reduced level, while the dominance of switching to IgG1 in the
      extrafollicular hapten-specific plasma cell response was retained. The up
      regulation of IL-4 message was not reduced or delayed in the absence of B cells
      and was only marginally reduced by the absence of IL-13. It is concluded that
      signals delivered by dendritic cells, which are not dependent on the presence of
      IL-4, IL-13, or B cells, can prime virgin T cells and induce the early Th2
      activities studied. These early events that direct virgin T cells toward Th2
      differentiation contrast with the critical later role of Th2 cytokines in
      selectively expanding Th2 clones and driving further IL-4 synthesis.

PMID- 12218105
TI  - Effects of nicotine exposure on T cell development in fetal thymus organ culture:
      arrest of T cell maturation.
AB  - There is evidence for both physiological functions of the natural
      neurotransmitter, acetylcholine, and pharmacological actions of the plant
      alkaloid, nicotine, on the development and function of the immune system. The
      effects of continuous exposure to nicotine over a 12-day course of fetal thymus
      organ culture (FTOC) were studied, and thymocytes were analyzed by flow
      cytometry. In the presence of very low concentrations of nicotine many more
      immature T cells (defined by low or negative TCR expression) and fewer mature T
      cells (intermediate or high expression of TCR) were produced. In addition, the
      numbers of cells expressing CD69 and, to a lesser extent, CD95 (Fas) were
      increased. These effects took place when fetal thymus lobes from younger (13-14
      days gestation) pups were used for FTOC. If FTOC were set up using tissue from
      older (15-16 days gestation pups), nicotine had little effect, suggesting that it
      may act only on immature T cell precursors. Consistent with an increase in
      immature cells, the expression of recombinase-activating genes was found to be
      elevated. Nicotine effects were partially blocked by the simultaneous addition of
      the nicotinic antagonist d-tubocurarine. Furthermore, d-tubocurarine alone
      blocked the development of both immature and mature murine thymocytes, suggesting
      the presence of an endogenous ligand that may engage nicotinic acetylcholine
      receptors on developing thymocytes and influence the course of normal thymic
      ontogeny.

PMID- 12218106
TI  - Expression of a functional eotaxin (CC chemokine ligand 11) receptor CCR3 by
      human dendritic cells.
AB  - Critical to the function of Ag-presenting dendritic cells (DCs) is their capacity
      to migrate to lymphoid organs and to sites of inflammation. A final stage of
      development, termed maturation, yields DCs that are strong stimulators of T cell
      mediated immunity and is associated with a remodeling of the cell surface that
      includes a change in the levels of expression of many molecules, including
      chemokine receptors. We show in this study that CCR3, a chemokine receptor
      initially discovered on eosinophils, is also expressed by human DCs that
      differentiate from blood monocytes, DCs that emigrate from skin (epidermal and
      dermal DCs), and DCs derived from CD34+ hemopoietic precursors in bone marrow,
      umbilical cord blood, and cytokine-elicited peripheral blood leukapheresis.
      Unlike other chemokine receptors, such as CCR5 and CCR7, the expression of CCR3
      is not dependent on the state of maturation. All DC subsets contain a large
      intracellular pool of CCR3. The surface expression of CCR3 is not modulated
      following uptake of particulate substances such as zymosan or latex beads. CCR3
      mediates in vitro chemotactic responses to the known ligands, eotaxin and eotaxin
      2, because the DC response to these chemokines is inhibited by CCR3-specific
      mAbs. We postulate that expression of CCR3 may underlie situations where both DCs
      and eosinophils accumulate in vivo, such as the lesions of patients with
      Langerhans cell granulomatosis.

PMID- 12218107
TI  - Structural elements of a protein antigen determine immunogenicity of the embedded
      MHC class I-restricted T cell epitope.
AB  - Substantial effort has been invested into optimization of vector structure, DNA
      formulation, or delivery methods to increase the effectiveness of DNA vaccines.
      In contrast, it has been only insufficiently explored how the higher order
      structure of an antigenic protein influences immunogenicity of embedded epitopes
      in vivo. Potent CD8+ T cell responses specific for a single immunogenic epitope
      are induced upon electrovaccination with plasmid DNA encoding the full-length
      heavy chain of the human HLA-Cw3 molecule. Contrary to expectations, a minimal
      construct, which provoked a substantial release of IFN-gamma from specific CTLs
      in vitro, did not induce a significant response in vivo. Systematically altered
      variants of the Cw3 molecule were thus tested both in vivo and in vitro to
      determine which structural parts are responsible for this discrepancy. In
      complementation experiments the participation of trans-acting helper epitopes was
      ruled out. Successive C-terminal truncations, human/mouse domain swap variants,
      and subdomain modifications defined the alpha3 region of the HLA heavy chain and
      membrane anchoring as critical elements. Based on these data, refined minimal
      constructs were engineered that triggered very high in vivo responses. The most
      advanced variant consisted only of an adenoviral leader, antigenic epitope,
      alpha3 domain, and 16 aa of the transmembrane domain. When a tumor Ag epitope was
      incorporated into one of these high performer minimal constructs, protection
      against melanoma metastases was attained upon vaccination. Thus, structural
      elements of the Ag can dominantly influence immunogenicity in vivo. These
      elements can also markedly improve the immunogenicity of unrelated Ags and may
      form the basis of a new generation of DNA vaccines.

PMID- 12218108
TI  - Anti-human CD4 induces peripheral tolerance in a human CD4+, murine CD4-, HLA-DR+
      advanced transgenic mouse model.
AB  - Selection in vivo of potent mAbs to human CD4 useful for immunotherapy, e.g., for
      the induction of immunological tolerance, is restricted for ethical reasons. We
      therefore used multiple transgenic mice that lack murine CD4, but express human
      CD4 specifically on Th cells, and HLA-DR3 as its natural counterligand (CD4/DR3
      mice). The injection of CD4/DR3 mice with anti-human CD4 (mAb Max.16H5) before
      immunization with tetanus toxoid (TT, day 0) totally blocked the formation of
      specific Abs. This state of unresponsiveness persisted a subsequent boost again
      performed in the presence of anti-human CD4. When these mice were left untreated
      for at least 40 days, and were then re-exposed with TT, but in the absence of
      anti-human CD4, they consistently failed to induce specific Abs (long-term
      unresponsiveness). Exposure to second party Ags (hen egg lysozyme, human
      acetylcholine receptor) induced specific Abs comparable with control mice,
      demonstrating that the anti-CD4-induced unresponsiveness was Ag specific
      (immunological tolerance). Importantly, the concurrent injection of TT and anti
      human CD4 at day 0, followed by another two anti-CD4 treatments, also led to
      tolerant animals, indicating that tolerance was inducible at the same day as the
      Ag exposure is provided. We finally demonstrate a limited ability of spleen cells
      to respond to TT in vitro, indicating that T cells are essentially involved in
      the maintenance of TT-specific tolerance. These data show for the first time that
      the human CD4 coreceptor mediates tolerance-inducing signals when triggered by an
      appropriate ligand in vivo.

PMID- 12218109
TI  - Innate immune response to malaria: rapid induction of IFN-gamma from human NK
      cells by live Plasmodium falciparum-infected erythrocytes.
AB  - To determine the potential contribution of innate immune responses to the early
      proinflammatory cytokine response to Plasmodium falciparum malaria, we have
      examined the kinetics and cellular sources of IFN-gamma production in response to
      human PBMC activation by intact, infected RBC (iRBC) or freeze-thaw lysates of P.
      falciparum schizonts. Infected erythrocytes induce a more rapid and intense IFN
      gamma response from malaria-naive PBMC than do P. falciparum schizont lysates
      correlating with rapid iRBC activation of the CD3(-)CD56(+) NK cell population to
      produce IFN-gamma. IFN-gamma(+) NK cells are detectable within 6 h of coculture
      with iRBC, their numbers peaking at 24 h in most donors. There is marked
      heterogeneity between donors in magnitude of the NK-IFN-gamma response that does
      not correlate with mitogen- or cytokine-induced NK activation or prior malaria
      exposure. The NK cell-mediated IFN-gamma response is highly IL-12 dependent and
      appears to be partially IL-18 dependent. Exogenous rIL-12 or rIL-18 did not
      augment NK cell IFN-gamma responses, indicating that production of IL-12 and IL
      18 is not the limiting factor explaining differences in NK cell reactivity
      between donors or between live and dead parasites. These data indicate that NK
      cells may represent an important early source of IFN-gamma, a cytokine that has
      been implicated in induction of various antiparasitic effector mechanisms. The
      heterogeneity of this early IFN-gamma response between donors suggests a
      variation in their ability to mount a rapid proinflammatory cytokine response to
      malaria infection that may, in turn, influence their innate susceptibility to
      malaria infection, malaria-related morbidity, or death from malaria.

PMID- 12218110
TI  - A role for the alpha-chain connecting peptide motif in mediating TCR-CD8
      cooperation.
AB  - To generate peripheral T cells that are both self-MHC restricted and self-MHC
      tolerant, thymocytes are subjected to positive and negative selection. How the
      TCR discriminates between positive and negative selection ligands is not well
      understood, although there is substantial evidence that the CD4 and CD8
      coreceptors play an important role in this cell fate decision. We have previously
      identified an evolutionarily conserved motif in the TCR, the alpha-chain
      connecting peptide motif (alpha-CPM), which allows the TCR to deliver positive
      selection signals. Thymocytes expressing alpha-CPM-deficient receptors do not
      undergo positive selection, whereas their negative selection is not impaired. In
      this work we studied the ligand binding and receptor function of alpha-CPM
      deficient TCRs by generating T cell hybridomas expressing wild-type or alpha-CPM
      deficient forms of the T1 TCR. This K(d)-restricted TCR is specific for a
      photoreactive derivative of the Plasmodium berghei circumsporozoite peptide(252
      260) IASA-YIPSAEK(ABA)I and is therefore amenable to TCR photoaffinity labeling.
      The experiments presented in this work show that alpha-CPM-deficient TCRs fail to
      cooperate with CD8 to enhance ligand binding and functional responses.

PMID- 12218111
TI  - Regeneration of natural antibody repertoire after massive ablation of lymphoid
      system: robust selection mechanisms preserve antigen binding specificities.
AB  - Natural Abs (NAbs) are Igs present in the serum and body fluids of healthy
      vertebrate animals, without any previous intentional immunization. NAbs often
      exhibit autoreactivity but also play an essential role in immunity, being a first
      line of defense against infectious microorganisms. We have previously analyzed
      the natural serum IgM Ab repertoire of normal mice, characterizing their
      reactivity with hundreds/thousands of self Ags; a significant similarity among
      different individuals was observed, and it was found that many reactivities of
      NAbs stably kept during adulthood were established early in life, implicating
      that period as a critical time window in the physiology of NAb repertoire
      selection. In the work reported here, experiments were conducted to address the
      role of normal lymphocyte ontogeny to the formation and stability of adult NAb
      repertoire. The massive destruction of the lymphoid system was promoted in adult
      mice with gamma-irradiation, and regeneration of hemopoietic tissues was granted
      by bone marrow or fetal liver inoculum. NAb repertoire regeneration was followed
      for 60 days after gamma-irradiation in bone marrow or fetal liver chimeric
      animals. The analysis of serum IgM reactivity with hundreds/thousands of self Ags
      showed that the NAb repertoire regenerated most of its original format after
      massive destruction of lymphoid compartments, characterizing autoreactive
      repertoire selection as a robust biological process. The data also show that
      regeneration of the NAb repertoire occurred similarly in fetal liver and bone
      marrow chimeras, although the latter animals poorly reconstituted their CD5(+) B1
      cell compartment, suggesting that B1 cells are not essential for natural Ab
      regeneration.

PMID- 12218112
TI  - Preventing NK cell activation by donor dendritic cells enhances allospecific CD4
      T cell priming and promotes Th type 2 responses to transplantation antigens.
AB  - Although much progress has been made in understanding the role of NK cells in
      bone marrow transplantation, little is known about their function in CD4 T cell
      mediated allograft rejection. We have previously shown that in the absence of CD8
      T lymphocyte priming, the in vivo default development pathway of alloreactive CD4
      T cells was strongly biased toward Th2 phenotype acquisition. In this study, we
      investigate the impact of NK cells on the activation and differentiation of
      alloreactive CD4 T cells in various donor/recipient combinations. Our data
      demonstrate that defective inhibition of host NK cells by donor APCs including
      dendritic cells (DCs) results in diminished allospecific Th cell responses
      associated with the development of effector Th cells producing IFN-gamma rather
      than type 2 cytokines. Turning host NK cells off was sufficient to restore strong
      alloreactive CD4 T cell priming and Th2 cell development. Similar results were
      obtained by analyzing the effect of NK cell activation on CD4 T cell responses to
      skin allografts. However, despite the dramatic effect of NK cells on alloreactive
      Th1/Th2 cell development, the kinetics of skin graft rejection were not affected.
      Thus, Th2 differentiation is a major pathway of alloreactive CD4 T cell
      development during solid organ transplant rejection, as long as host NK and CD8 T
      cells are not activated. We propose the hypothesis that MHC class I-driven
      interactions between donor DCs and host NK cells or CD8 T cells might result in
      DC-carried signals controlling the dynamics of alloreactive CD4 T cell priming
      and polarization.

PMID- 12218113
TI  - Recruitment of CTL activity by tumor-specific antibody-mediated targeting of
      single-chain class I MHC-peptide complexes.
AB  - The MHC class I-restricted CD8 CTL effector arm of the adaptive immune response
      is uniquely equipped to recognize tumor cells as foreign and consequently
      initiates the cascade of events resulting in their destruction. However, tumors
      have developed sophisticated strategies to escape immune effector mechanisms;
      their most well-known strategy is down-regulation of MHC class I molecules. To
      overcome this and develop new approaches for immunotherapy, we have constructed a
      recombinant molecule in which a single-chain MHC is specifically targeted to
      tumor cells through its fusion to cancer-specific recombinant Ab fragments. As a
      model we used a single-chain HLA-A2 molecule genetically fused to the variable
      domains of an anti-IL-2Ralpha subunit-specific humanized Ab, anti-Tac. The
      construct, termed B2M-aTac(dsFv), was expressed in Escherichia coli, and
      functional molecules were produced by in vitro refolding in the presence of HLA
      A2-restricted antigenic peptides. Flow cytometry studies revealed the ability to
      decorate Ag-positive, HLA-A2-negative human tumor cells with HLA-A2-peptide
      complexes in a manner that was entirely dependent upon the specificity of the
      targeting Ab fragment. Most importantly, the B2M-aTac(dsFv)-mediated coating of
      the target tumor cells made them susceptible for efficient and specific HLA-A2
      restricted, melanoma gp100 peptide-specific CTL-mediated lysis. These results
      demonstrate the concept that Ab-guided, Ag-specific targeting of MHC-peptide
      complexes on tumor cells can render them susceptible and more receptive and thus
      potentiate CTL killing. This type of approach may open the way for the
      development of new immunotherapeutic strategies based on Ab targeting of natural
      cognate MHC ligands and CTL-based cytotoxic mechanisms.

PMID- 12218114
TI  - TCR signals mediated by Src family kinases are essential for the survival of
      naive T cells.
AB  - The role of TCR signals triggered by recognition of self MHCs in maintaining the
      survival of naive peripheral T cells remains controversial. Here we examine the
      role of the Src family kinases, p56(lck) (Lck) and p59(fyn) (Fyn), in the
      survival of naive T cells. We show that long term survival requires a combination
      of signals transduced by Src family kinases and signals through the IL-7R. In the
      absence of either one, naive T cells die slowly, but if both signals are removed,
      cell loss is greatly accelerated. The TCR signal can be mediated by either Fyn or
      Lck at wild-type levels of expression, but not by Lck alone if expressed
      suboptimally. The disappearance of T cells in the absence of Fyn and Lck was
      associated with a complete loss of TCRzeta-chain phosphorylation and down
      regulation of CD5, both of which are also MHC contact dependent, indicating that
      the Src family kinases are critical for transducing a TCR-MHC survival signal.

PMID- 12218115
TI  - Bcl-2 controls dendritic cell longevity in vivo.
AB  - Dendritic cells (DC) were found to down-regulate Bcl-2 protein upon maturation in
      vivo. Because Bcl-2 has been shown to exert anti-apoptotic functions, down
      regulation of Bcl-2 could be a mechanism by which DC longevity is controlled. To
      dysregulate this potential control system and to study the role of Bcl-2 in DC,
      we expressed human Bcl-2 under control of the murine CD11c-promoter as a
      transgene specifically in DC and show that DC frequencies and numbers increase in
      transgenic mice. In vivo bromodeoxyuridin, as well as adoptive, DC transfer
      studies show that the relative turnover/survival of mature Bcl-2 transgenic DC is
      increased. This had a direct impact on CD4+ T cell, as well as humoral immune,
      responses, which were elevated in transgenic animals. When Bcl-2 transgenic DC
      were used as DC vaccines, they induced 2- to 3-fold greater expansion of Ag
      specific CTL, and stronger in vivo cytotoxicity. Overall, these data indicate
      that down-regulation of Bcl-2 controls DC longevity, which in turn directly
      regulates immune responses and the efficacy of DC when used as vaccines.

PMID- 12218116
TI  - Major differences in antigen-processing correlate with a single Arg71<-->Lys
      substitution in HLA-DR molecules predisposing to rheumatoid arthritis and with
      their selective interactions with 70-kDa heat shock protein chaperones.
AB  - Several HLA-DR alleles are genetically associated with rheumatoid arthritis.
      DRB1*0401 predominates in Northern Europe and has a characteristic (70)QKRAA
      motif. This sequence contacts bound peptides and the TCR. Further interactions
      have been suggested with additional proteins during Ag loading. We explored the
      much stronger processing/presentation of full-length recombinant human
      acetylcholine receptor alpha subunit to a specific T cell clone by APC from
      DRB1*0401+ than *0408+ donors. Using DR*04 transfectants, we show that this
      difference results largely from the single Lys71<-->Arg interchange (0401<-
      >0408), which scarcely affects epitope binding, rather than from any other
      associated polymorphism. Furthermore, we proved our recombinant polypeptides to
      contain the Escherichia coli 70-kDa heat shock protein molecule DnaK and its
      requirement for efficient processing and presentation of the epitope by
      DRB1*0401+ cells. According to a recent report, 70-kDa heat shock protein
      chaperones preferentially bind to the QKRAA, rather than the QRRAA, motif.
      Variations between the shared epitope motifs QKRAA and QRRAA are emphasized by
      underlining. We propose that such interactions enhance the intracellular epitope
      loading of *0401 molecules. They may thus broaden immune responses to pathogens
      and at least partially explain the distinct contributions of DRB1*0401 and other
      alleles to disease predisposition.

PMID- 12218117
TI  - Active form of Notch imposes T cell fate in human progenitor cells.
AB  - The crucial role of Notch signaling in cell fate decisions in hematopoietic
      lineage and T lymphocyte development has been well established in mice.
      Overexpression of the intracellular domain of Notch mediates signal transduction
      of the protein. By retroviral transduction of this constitutively active
      truncated intracellular domain in human CD34+ umbilical cord blood progenitor
      cells, we were able to show that, in coculture with the stromal MS-5 cell line,
      depending on the cytokines added, the differentiation toward CD19+ B lymphocytes
      was blocked, the differentiation toward CD14+ monocytes was inhibited, and the
      differentiation toward CD56+ NK cells was favored. The number of CD7+cyCD3+
      cells, a phenotype similar to T/NK progenitor cells, was also markedly increased.
      In fetal thymus organ culture, transduced CD34+ progenitor cells from umbilical
      cord blood cells or from thymus consistently generated more TCR-gammadelta T
      cells, whereas the other T cell subpopulations were largely unaffected.
      Interestingly, when injected in vivo in SCID-nonobese diabetic mice, the
      transduced cells generated ectopically human CD4+CD8+ TCR-alphabeta cells in the
      bone marrow, cells that are normally only present in the thymus, and lacked B
      cell differentiation potential. Our results show unequivocally that, in human,
      Notch signaling inhibits the monocyte and B cell fate, promotes the T cell fate,
      and alters the normal T cell differentiation pathway compatible with a pretumoral
      state.

PMID- 12218118
TI  - Autocrine IL-4 gene regulation at late phases of TCR activation in differentiated
      Th2 cells.
AB  - IL-4 is a multifunctional cytokine whose secretion displays important
      immunomodulatory functions. Its expression is regulated at the level of
      transcription, and one of the main factors involved is NFAT. The IL-4-induced
      transcription factor Stat6 is required for the development of naive T cells into
      Th2 phenotype, capable of secreting IL-4. However, IL-4 production by
      differentiated Th2 cells is IL-4 independent; thus, it remains unclear whether
      Stat6 plays any role in the IL-4 expression by mature Th2 cells. We have analyzed
      in the Th2 clone D10.G4.1 the nuclear proteins able to bind the regulatory
      element P1 of the IL-4 promoter. Gel-shift assays show NFAT1 as the most abundant
      nuclear protein that binds to P1 after ionomycin plus PMA activation, whereas
      Stat6 accounts for the bulk of the P1 binding in the presence of exogenous IL-4.
      Reporter experiments agree with an inhibitory effect of Stat6 on the NFAT1
      induced transcriptional activity directed by the P1 element. CD3 signaling leads
      to an early induction of NFAT1-P1 complexes correlating with a strong induction
      of the IL-4 gene. In later phases of CD3 activation, P1 is also bound by Stat6
      and a fall in the IL-4 mRNA levels takes place. These two late events during CD3
      activation were found to be sensible in experiments conducted with an anti-IL-4
      Ab. These results suggest that IL-4 endogenously produced by Th2 cells under TCR
      triggering modulates its own expression through Stat6.

PMID- 12218119
TI  - Loss of type I IFN receptors and impaired IFN responsiveness during terminal
      maturation of monocyte-derived human dendritic cells.
AB  - Type I IFNs are modulators of myeloid dendritic cell (DC) development, survival,
      and functional activities. Here we monitored the signal transduction pathway
      underlying type I IFN biological activities during in vitro maturation of human
      monocyte-derived DCs. IFN-inducible tyrosine phosphorylation of STAT family
      members was severely impaired upon LPS-induced DC maturation. This correlated
      with a marked reduction of both type I IFN receptor chains occurring as early as
      4 h after LPS treatment. The reduced receptor expression was a post
      transcriptional event only partially mediated by ligand-induced
      internalization/degradation. In fact, although an early and transient production
      of type I IFNs was observed after LPS treatment, its neutralization was not
      sufficient to completely rescue IFN receptor expression. Notably, neutralization
      of LPS-induced, endogenous type I IFNs did not interfere with the acquisition of
      a fully mature surface phenotype, nor did it have a significant effect on the
      allostimulatory properties of LPS-stimulated DCs. Overall, these data indicate
      that DCs strictly modulate their responsiveness to type I IFNs as part of their
      maturation program, underlining the importance of the IFN system in the
      regulation of DC physiology.

PMID- 12218120
TI  - Regulation of immunoproteasome subunit expression in vivo following pathogenic
      fungal infection.
AB  - The proteasome catalytic beta subunits LMP2, LMP7, and MECL-1 and two proteasome
      activator proteins, PA28 alpha and beta, are induced following exposure to IFN
      gamma in vitro. Induction of these immunosubunits and the PA28 alpha/beta hetero
      oligomer alters proteasome catalytic functions and specificity and enhances
      production of certain MHC class I epitopes. We sought to determine whether and to
      what extent proteasome subunit composition is regulated in vivo and to elucidate
      the mechanisms of such regulation. We analyzed basal expression levels of these
      inducible genes in normal, IFN-gamma-deficient, and Stat-1-deficient mice. Mice
      of all three genotypes display constitutive expression of the immunosubunits and
      PA28, demonstrating that basal expression in vivo is independent of endogenous
      IFN-gamma production. However, basal expression levels are reduced in Stat-1(-/-)
      mice, demonstrating a role for Stat-1 independent of IFN-gamma signaling. To
      demonstrate that IFN-gamma can induce these genes in vivo, mice were infected
      with Histoplasma capsulatum. Elevated expression of these genes followed the same
      time course as IFN-gamma expression in infected mice. IFN-gamma-deficient mice
      did not display elevated protein expression following infection, suggesting that
      other inflammatory cytokines produced in infected mice are unable to influence
      proteasome expression. Cytokines other than IFN-gamma also failed to influence
      proteasome gene expression in vitro in cell lines that had no basal expression of
      LMP2, LMP7, or MECL-1. Thus, both in vitro and in vivo data demonstrate that IFN
      gamma is essential for up-regulation, but not constitutive expression, of
      immunoproteasome subunits in mice.

PMID- 12218121
TI  - TNF-mediated toxicity after massive induction of specific CD8+ T cells following
      immunization of mice with a tumor-specific peptide.
AB  - We immunized mice with antigenic peptide P815E, which is presented by H-2K(d) and
      recognized by tumor-specific CTL raised against P815 tumor cells. This peptide is
      encoded by the ubiquitously expressed gene MsrA and carries a mutated residue
      conferring tumor specificity. Unexpectedly, we observed a severe toxicity
      occurring in the early hours after the third injection, resulting in the death of
      most mice within 24 h. The toxic syndrome was reminiscent of TNF-induced shock,
      and the sera of ill mice contained high levels of TNF. Toxicity was prevented by
      injection of neutralizing anti-TNF Abs, confirming the involvement of TNF.
      Depletion of CD8+ T cells could also prevent toxicity, and ex vivo experiments
      confirmed that CD8+ lymphocytes were the major cellular source of TNF in
      immunized mice. Tetramer analysis of the lymphocytes of immunized mice indicated
      a massive expansion of P815E-specific T cells, up to >60% of circulating CD8+
      lymphocytes. A similar toxicity was observed after massive expansion of specific
      CD8+ T cells following immunization with another P815 peptide, which is encoded
      by gene P1A and was injected in a form covalently linked to an immunostimulatory
      peptide derived from IL-1. We conclude that the toxicity is caused by specific
      CD8+ lymphocytes, which are extensively amplified by peptide immunization in a
      QS21-based adjuvant and produce toxic levels of TNF upon further stimulation with
      the peptide. Our results suggest that immunotherapy trials involving new peptides
      should be pursued with caution and should include a careful monitoring of the T
      cell response.

PMID- 12218122
TI  - Peripheral immature CD2-/low T cell development from type 2 to type 1 cytokine
      production.
AB  - Immature myeloid and NK cells exist, and undergo cytokine-induced
      differentiation, in the periphery. In this study, we show that also immature CD2(
      /low) T cells exist in peripheral blood. These cells produce the type 2 cytokines
      IL-13, IL-4, and IL-5, but not IFN-gamma or IL-10, and, upon culture with IL-12-
      and TCR-mediated stimuli, differentiate to IL-13(+)IFN-gamma(+) cells producing
      high IL-2 levels, and finally IL-13(-)IFN-gamma(+) cells. The monokine
      combination IL-12, IL-18, and IFN-alpha substitutes for TCR-mediated stimulation
      to induce the same differentiation process in both immature CD2(-/low) and
      primary mature CD2(+) IL-13(+) T cells. IFN-alpha is needed to maintain high
      level IL-2 production, which is confined to type 2 cytokine-producing cells and
      lost in the IFN-gamma(+) ones. Upon TCR-mediated stimulation, IFN-gamma(+) cells
      are then induced to produce IL-10 as they undergo apoptosis. These data indicate
      that peripheral type 2 cytokine(+) T cells are immature cells that can
      differentiate to effector IFN-gamma(+) cells following a linear monokine
      regulated pathway identical with that previously described for NK cells. They
      define the cellular bases to support that cell-mediated immune responses are
      regulated not only via Ag-induced activation of mature effector cells, but also
      via bystander monokine-induced maturation of immature T cells.

PMID- 12218123
TI  - Gene conversion-like sequence transfers between transgenic antibody V genes are
      independent of RAD54.
AB  - Homology-based Ig gene conversion is a major mechanism for Ab diversification in
      chickens and the Rad54 DNA repair protein plays an important role in this
      process. In mice, although gene conversion appears to be rare among endogenous Ig
      genes, Ab H chain transgenes undergo isotype switching and gene conversion-like
      sequence transfer processes that also appear to involve homologous recombination
      or gene conversion. Furthermore, homology-based DNA repair has been suggested to
      be important for somatic mutation of endogenous mouse Ig genes. To assess the
      role of Rad54 in these mouse B cell processes, we have analyzed H chain transgene
      isotype switching, sequence transfer, and somatic hypermutation in mice that lack
      RAD54. We find that Rad54 is not required for either transgene switching or
      transgene hypermutation. Furthermore, even transgene sequence transfers that are
      known to require homology-based recombinations are Rad54 independent. These
      results indicate that mouse B cells must use factors for promoting homologous
      recombination that are distinct from the Rad54 proteins important in homology
      based chicken Ab gene recombinations. Our findings also suggest that mouse H
      chain transgene sequence transfers might be more closely related to an error
      prone homology-based somatic hypermutational mechanism than to the
      hyperconversion mechanism that operates in chicken B cells.

PMID- 12218124
TI  - Grafting of "abbreviated" complementarity-determining regions containing
      specificity-determining residues essential for ligand contact to engineer a less
      immunogenic humanized monoclonal antibody.
AB  - Murine mAb COL-1 reacts with carcinoembryonic Ag (CEA), expressed on a wide range
      of human carcinomas. In preclinical studies in animals and clinical trials in
      patients, murine COL-1 showed excellent tumor localization. To circumvent the
      problem of immunogenicity of the murine Ab in patients, a humanized COL-1 (HuCOL
      1) was generated by grafting the complementarity-determining regions (CDRs) of
      COL-1 onto the frameworks of the variable light and variable heavy regions of
      human mAbs. To minimize anti-V region responses, a variant of HuCOL-1 was
      generated by grafting onto the human frameworks only the "abbreviated" CDRs, the
      stretches of CDR residues that contain the specificity-determining residues that
      are essential for the surface complementarity of the Ab and its ligand. In
      competition RIAs, the recombinant variant completely inhibited the binding of
      radiolabeled murine and humanized COL-1 to CEA. The HuCOL-1 and its variant
      showed no difference in their binding ability to the CEA expressed on the surface
      of a CEA-transduced tumor cell line. Compared with HuCOL-1, the HuCOL-1 variant
      showed lower reactivity to patients' sera carrying anti-V region Abs to COL-1.
      The final variant of the HuCOL-1, which retains its Ag-binding reactivity and
      shows significantly lower serum reactivity than that of the parental Ab, can
      serve as a prototype for the development of a potentially useful clinical
      reagent.

PMID- 12218125
TI  - DNA alkylating agents alleviate silencing of class II transactivator gene
      expression in L1210 lymphoma cells.
AB  - MHC class II (Ia) Ag expression is inversely correlated with tumorigenicity and
      directly correlated with immunogenicity in clones of the mouse L1210 lymphoma (1
      ). Understanding the mechanisms by which class II Ag expression is regulated in
      L1210 lymphoma may facilitate the development of immunotherapeutic approaches for
      the treatment of some types of lymphoma and leukemia. This study demonstrates
      that the variation in MHC class II Ag expression among clones of L1210 lymphoma
      is due to differences in the expression of the class II transactivator (CIITA).
      Analysis of stable hybrids suggests that CIITA expression is repressed by a
      dominant mechanism in class II-negative L1210 clones. DNA-alkylating agents such
      as ethyl methanesulfonate and the chemotherapeutic drug melphalan activate CIITA
      and class II expression in class II negative L1210 cells, and this effect appears
      to be restricted to transformed cell lines derived from the early stages of B
      cell ontogeny. Transient transfection assays demonstrated that the CIITA type III
      promoter is active in class II(-) L1210 cells, despite the fact that the
      endogenous gene is not expressed, which suggests that these cells have all of the
      transacting factors necessary for CIITA transcription. An inverse correlation
      between methylation of the CIITA transcriptional regulatory region and CIITA
      expression was observed among L1210 clones. Furthermore, 5-azacytidine treatment
      activated CIITA expression in class II-negative L1210 cells. Collectively, our
      results suggest that 1) CIITA gene expression is repressed in class II(-) L1210
      cells by methylation of the CIITA upstream regulatory region, and 2) treatment
      with DNA-alkylating agents overcomes methylation-based silencing of the CIITA
      gene in L1210 cells.

PMID- 12218126
TI  - Variable diversity joining recombination: nonhairpin coding ends in thymocytes of
      SCID and wild-type mice.
AB  - Initiation of V(D)J recombination results in broken DNA molecules with blunt
      recombination signal ends and covalently sealed (hairpin) coding ends. In SCID
      mice, coding joint formation is severely impaired and hairpin coding ends
      accumulate as a result of a deficiency in the catalytic subunit of DNA-dependent
      protein kinase, an enzyme involved in the repair of DNA double-strand breaks. In
      this study, we report that not all SCID coding ends are hairpinned. We have
      detected open Jdelta1 and Ddelta2 coding ends at the TCRdelta locus in SCID
      thymocytes. Approximately 25% of 5'Ddelta2 coding ends were found to be open.
      Large deletions and abnormally long P nucleotide additions typical of SCID
      Ddelta2-Jdelta1 coding joints were not observed. Most Jdelta1 and Ddelta2 coding
      ends exhibited 3' overhangs, but at least 20% had unique 5' overhangs not
      previously detected in vivo. We suggest that the SCID DNA-dependent protein
      kinase deficiency not only reduces the efficiency of hairpin opening, but also
      may affect the specificity of hairpin nicking, as well as the efficiency of
      joining open coding ends.

PMID- 12218127
TI  - Polymorphism at position 97 in MHC class I molecules affects peptide specificity,
      cell surface stability, and affinity for beta2-microglobulin.
AB  - The two mouse MHC class I alleles, L(d) and L(q), share complete amino acid
      sequence identity except in the alpha2 domain, where they differ at six
      positions. Despite their similarity, L(q) has a stronger association with beta2
      microglobulin (beta2m), is expressed at higher levels on the cell surface,
      demonstrates an increased cell surface half-life, and has fewer open forms on the
      cell surface than L(d). To determine the basis for their phenotypic differences,
      L(d) molecules containing chimeric L(d)-L(q) alpha2 domains were characterized,
      and these analyses implicated residue 97 (L(d)Trp and L(q)Arg) as the polymorphic
      site responsible for the disparity in beta2m association between the two alleles.
      Single substitution analysis at this site (L(d)W97R and L(q)R97W) confirmed this.
      Furthermore, the L(d)W97R mutant molecule has a longer cell surface half-life
      than either L(q) or L(d), and fewer open forms of L(d)W97R are observed on the
      cell surface. In addition, both L(d)W97R and L(q) possess decreased binding
      affinity for the L(d)-restricted tum(-) P91A(14-22) peptide compared with L(d).
      Collectively, these results and the known location of Trp(97) in the peptide
      binding cleft of L(d) strongly suggest that the substitution of Arg for Trp(97)
      in L(d) alters the peptide binding cleft, increasing its affinity for endogenous
      peptides, which results in greater cell surface stability and better retention of
      beta2m. Furthermore, these results imply that Trp(97) plays an important role in
      the ability of L(d) to efficiently participate in alternative MHC class I Ag
      presentation pathways.

PMID- 12218128
TI  - Regulation and specificity of MHC2TA promoter usage in human primary T
      lymphocytes and cell line.
AB  - Although activated human T cells express MHC class II antigens, the regulation of
      these antigens in T cells is poorly understood. This study focuses on the control
      of the MHC2TA gene in these cells. MHC2TA encodes the transcriptional master
      regulator of MHC class II, the class II trans-activator (CIITA). It has at least
      three distinct promoters (PI, PIII, and PIV), each active in an overlapping
      subset of cell types and directing a slightly different product. This report used
      highly purified blood T cells prepared by negative immunoselection to analyze
      CIITA. Real-time PCR analysis indicates that resting T cells do not express
      detectable CIITA transcript, while activated T cells express the PIII CIITA form.
      Transient transfection of activated blood T cells using wild-type and mutant PIII
      promoter-reporter constructs shows that two promoter elements, activation
      response element-1 (ARE-1) and ARE-2, are important for PIII function. cAMP
      response element binding protein, a known activator of gene expression in
      activated T cells, activates PIII in primary T cells. However, an intact ARE-2
      site is not required for this activation, indicating that cAMP response element
      binding protein does not activate via this site. EMSAs indicate that an
      activating transcription factor/cAMP response element binding protein/cAMP
      response element modulator family member, but not phosphorylated cAMP response
      element binding protein-1, binds to ARE-2. ARE-2 also forms a complex with an
      unidentified protein. The ARE-2 binding protein is constitutively expressed in a
      DR(+) T cell line, reflecting differences between the DR(+) cell line and primary
      blood lymphocytes. These results show that MHC2TA PIII is induced in activated T
      lymphocytes, and that the induced binding of ARE-2 is a crucial step in this
      process.

PMID- 12218129
TI  - Regulation of IFN regulatory factor 4 expression in human T cell leukemia virus-I
      transformed T cells.
AB  - IFN regulatory factor (IRF)-4 is a lymphoid/myeloid-restricted member of the IRF
      transcription factor family that plays an essential role in the homeostasis and
      function of mature lymphocytes. IRF-4 expression is tightly regulated in resting
      primary T cells and is transiently induced at the mRNA and protein levels after
      activation by Ag-mimetic stimuli such as TCR cross-linking or treatment with
      phorbol ester and calcium ionophore (PMA/ionomycin). However, IRF-4 is
      constitutively upregulated in human T cell leukemia virus type I (HTLV-I)
      infected T cells as a direct gene target for the HTLV-I Tax oncoprotein. In this
      study we demonstrate that chronic IRF-4 expression in HTLV-I-infected T
      lymphocytes is associated with a leukemic phenotype, and we examine the
      mechanisms by which continuous production of IRF-4 is achieved in HTLV-I
      transformed T cells. IRF-4 expression in HTLV-1-infected cells is driven through
      activation of the NF-kappaB and NF-AT pathways, resulting in the binding of p50,
      p65, and c-Rel to the kappaB1 element and p50, c-Rel, and NF-ATp to the CD28RE
      element within the -617 to -209 region of the IRF-4 promoter. Furthermore,
      mutation of either the kappaB1 or CD28RE sites blocks Tax-mediated
      transactivation of the human IRF-4 promoter in T cells. These experiments
      constitute the first detailed analysis of human IRF-4 transcriptional regulation
      within the context of HTLV-I infection and transformation of CD4(+) T
      lymphocytes.

PMID- 12218130
TI  - Identification of a novel HLA-B60-restricted T cell epitope of the minor
      histocompatibility antigen HA-1 locus.
AB  - The polymorphic minor histocompatibility Ag HA-1 locus encodes two peptides, HA
      1(H) and HA-1(R), with a single amino acid difference. Whereas the immunogenicity
      of the HA-1(R) allele has not yet been shown, the nonameric HA-1(H) peptide
      induces HLA-A2-restricted cytotoxic T cells in vivo and in vitro. It is not known
      whether the mHag HA-1(H) or HA-1(R) associates with other HLA class I molecules.
      Therefore, the polymorphic regions of both HA-1 alleles were analyzed to identify
      HLA class I binding peptides that are properly processed by proteasomal
      degradation. Peptide binding analyses were performed for all nonameric HA-1(H/R)
      peptides for binding to nine HLA class I molecules with >10% prevalence in the
      Caucasian population and for seven nonameric/decameric HA-1(H/R) peptides
      predicted to bind to HLA-A3, -B14, and -B60. Only the nonameric KECVL(H)/(R)DDL
      and decameric KECVL(H)/(R)DDLL peptides showed strong and stable binding to HLA
      B60. In vitro digestion of 29-aa-long HA-1 peptides by purified 20S proteasomes
      revealed proper cleavage at the COOH termini of both HLA-B60 binding HA-1(H) and
      HA-1(R) peptides. In subsequent analyses, dendritic cells pulsed with the
      nonameric HA-1(R) peptide did not induce CTLs that recognize the natural HLA
      B60/HA-1(R) ligand. In contrast, dendritic cells pulsed with the nonameric HA
      1(H) peptide induced IFN-gamma-secreting T cells specific for the natural HLA
      B60/HA-1(H) ligand in three HLA-B60(+) HA-1(RR) individuals, demonstrating the
      immunogenicity of the HLA-B60/HA-1(H) ligand. In conclusion, this study shows a
      novel HLA-B60-restricted T cell epitope of the minor histocompatibility Ag HA-1
      locus.

PMID- 12218131
TI  - Peptidic termini play a significant role in TCR recognition.
AB  - TCR recognition of class I MHC is dependent on the composition of the antigenic
      peptide and the MHC. Single amino acid substitutions in either the MHC or the
      peptide may dramatically alter recognition. While the major interactions between
      TCR and the peptide/MHC complex appear to be focused on the complementarity
      determining region (CDR)3, it is also clear from the cocrystal structure of class
      I MHC and TCR that the amino and carboxyl ends of the peptide may play a role
      through interactions with the CDR1. In this work we show that gp33 variants
      substituted at the peptidic termini at the putative CDR1 contact regions show
      improved recognition in B6 mice. The rank order of recognition is different using
      the P14 transgenic T cells, suggesting that one reason for improved recognition
      is a change in the TCR repertoire that recognizes the peptide. However, the
      affinity of the TCR by some of the peptide/MHC complex with increased recognition
      is improved, as shown by increased tetramer binding to P14 T cells. These
      substitutions at the termini of the peptide-binding cleft cause localized
      conformational changes as seen by changes in mAb binding and crystallographic
      structures. The different peptide structures also show different conformations in
      the center of the peptide, but these are shown to be energetically similar and
      thus most likely have no significance with respect to TCR recognition. Therefore,
      small conformational changes, localized to the CDR1 contact regions, may play a
      significant role in TCR recognition.

PMID- 12218132
TI  - MHC allele-specific molecular features determine peptide/HLA-A2 conformations
      that are recognized by HLA-A2-restricted T cell receptors.
AB  - The structures of alphabeta TCRs bound to complexes of class I MHC molecules and
      peptide show that the TCRs make multiple contacts with the alpha1 and alpha2
      helixes of the MHC. Previously we have shown that the A6 TCR in complex with the
      HLA-A2/Tax peptide has 15 contact sites on HLA-A2. Single amino acid mutagenesis
      of these contact sites demonstrated that mutation of only three amino acids
      clustered on the alpha1 helix (R65, K66, A69) disrupted recognition by the A6
      TCR. In the present study we have asked whether TCRs that recognize four other
      peptides presented by HLA-A2 interact with the MHC in identical, similar, or
      different patterns as the A6 TCR. Mutants K66A and Q155A had the highest
      frequency of negative effects on lysis. A subset of peptide-specific CTL also
      selectively recognized mutants K66A or Q155A in the absence of exogenous cognate
      peptides, indicating that these mutations affected the presentation of endogenous
      peptide/HLA-A2 complexes. These findings suggest that most HLA-A2-restricted TCRs
      recognize surfaces on the HLA-A2/peptide complex that are dependent upon the side
      chains of K66 and Q155 in the central portion of the peptide binding groove.
      Crystallographic structures of several peptide/HLA-A2 structures have shown that
      the side chains of these critical amino acids that make contact with the A6 TCR
      also contact the bound peptide. Collectively, our results indicate that the
      generalized effects of changes at these critical amino acids are probably due to
      the fact that they can be directly contacted by TCRs as well as influence the
      binding and presentation of the bound peptides.

PMID- 12218133
TI  - Toll-like receptor 4 expression is required to control chronic Mycobacterium
      tuberculosis infection in mice.
AB  - Endotoxin from Gram-negative bacteria bound to CD14 signals through Toll-like
      receptor (TLR) 4, while components of Gram-positive bacteria, fungi, and
      Mycobacterium tuberculosis (M.tb.) preferentially use TLR2 signaling. We asked
      whether TLR4 plays any role in host resistance to M.tb. infection in vivo.
      Therefore, we infected the TLR4 mutant C3H/HeJ mice and their controls, C3H/HeN
      mice, with M.tb. by aerosol. TLR4 mutant mice had a reduced capacity to eliminate
      mycobacteria from the lungs, spread the infection to spleen and liver, with 10
      100 times higher CFU organ levels than the wild-type mice and succumbed within 5
      7 mo, whereas most of the wild-type mice controlled infection and survived the
      duration of the experiment. The lungs of TLR4 mutant mice showed chronic
      pneumonia with increased neutrophil infiltration, reduced macrophages
      recruitment, and abundant acid-fast bacilli. Furthermore, the pulmonary
      expression of TNF-alpha, IL-12p40, and monocyte chemoattractant protein 1 was
      significantly lower in C3H/HeJ mice when compared with the wild-type controls.
      C3H/HeJ-derived macrophages infected in vitro with M.tb. produced lower levels of
      TNF-alpha. Finally, the purified mycobacterial glycolipid, phosphatidylinositol
      mannosides, induced signaling in both a TLR2- and TLR4-dependent manner, thus
      suggesting that recognition of phosphatidylinositol mannosides in vivo may
      influence the development of protective immunity. In summary, macrophage
      recruitment and the proinflammatory response to M.tb. are impaired in TLR4 mutant
      mice, resulting in chronic infection with impaired elimination of mycobacteria.
      Therefore, TLR4 signaling is required to mount a protective response during
      chronic M.tb. infection.

PMID- 12218134
TI  - Gamma/delta T cell-deficient mice exhibit reduced disease severity and decreased
      inflammatory response in the brain in murine neurocysticercosis.
AB  - In a recently developed mouse model for neurocysticercosis, the immune response
      was characterized by a massive influx of gammadelta T cells and a type 1 pathway
      of cytokine expression. To understand the role of gammadelta T cells during this
      infection, the cellular and cytokine response was analyzed in mice that lack
      gammadelta T cells (TCRdelta(-/-)). In TCRdelta(-/-) mice, Mesocestoides corti
      metacestodes preferentially invaded the extraparenchymal areas of the brain.
      Furthermore, parasites were able to escape from the brain and establish a
      systemic infection with liver and peritoneal involvement. Immunopathological
      studies indicated that TCRdelta(-/-) mice develop little inflammatory response
      and less neurological symptomatology. Significantly reduced numbers of T cells,
      macrophages, dendritic cells, and mast cells were present in the brain. The
      cytokine response in the brain of TCRdelta(-/-) mice appears to be a mixed
      type1/type 2 response with low levels of IL-2, IL-4, IL-10, IL-12, IL-13, IL-15,
      and IFN-gamma. To further investigate the immunological significance of this cell
      population, gammadelta T cells were adoptively transferred into intracranially
      infected TCRdelta(-/-) mice. gammadelta T cells were specifically recruited into
      the CNS in response to this parasitic infection, and they were able to target the
      infected brain within 12 h after transfer. These results suggest that gammadelta
      T cells are key players in the immune response elicited during this CNS infection
      and direct a type 1 response in wild-type mice upon infection.

PMID- 12218135
TI  - Caspase-9/-3 activation and apoptosis are induced in mouse macrophages upon
      ingestion and digestion of Escherichia coli bacteria.
AB  - A number of highly virulent, intracellular bacteria are known to induce cell
      death by apoptosis in infected host cells. In this work we demonstrate that
      phagocytosis of bacteria from the Escherichia coli laboratory strain K12 DH5alpha
      is a potent cell death stimulus for mouse macrophages. RAW264.7 mouse macrophages
      took up bacteria and digested them within 2-4 h as investigated with green
      fluorescent protein-expressing bacteria. No evidence of apoptosis was seen at 8 h
      postexposure, but at 24 h approximately 70% of macrophages displayed an apoptotic
      phenotype by a series of parameters. Apoptosis was blocked by inhibition of
      caspases or by forced expression of the apoptosis-inhibiting protein Bcl-2.
      Processing of caspase-3 and caspase-9 but not caspase-8 was seen suggesting that
      the mitochondrial branch of the apoptotic pathway was activated. Active effector
      caspases could be detected in two different assays. Because the adapter molecule
      myeloid differentiation factor 88 (MyD88) has been implicated in apoptosis,
      involvement of the Toll-like receptor pathway was investigated. In RAW264.7
      cells, heat-treated bacteria were taken up poorly and failed to induce
      significant apoptosis. However, cell activation was almost identical between live
      and heat-inactivated bacteria as measured by extracellular signal-regulated
      kinase activation, generation of free radicals, and TNF secretion. Furthermore,
      primary bone marrow-derived macrophages from wild-type as well as from MyD88
      deficient mice underwent apoptosis upon phagocytosis of bacteria. These results
      show that uptake and digestion of bacteria leads to MyD88-independent apoptosis
      in mouse macrophages. This form of cell death might have implications for the
      generation of the immune response.

PMID- 12218136
TI  - CD80+Gr-1+ myeloid cells inhibit development of antifungal Th1 immunity in mice
      with candidiasis.
AB  - To find out whether polymorphonuclear neutrophils (PMN), abundantly recruited in
      disseminated Candida albicans infection, could directly affect the activation of
      Th cells we addressed the issues as to whether murine PMN, like their human
      counterparts, express costimulatory molecules and the functional consequence of
      this expression in terms of antifungal immune resistance. To this purpose, we
      assessed 1) the expression of CD80 (B7-1) and CD86 (B7-2) molecules on
      peripheral, splenic, and inflammatory murine Gr-1+ PMN; 2) its modulation upon
      interaction with C. albicans in vitro, in vivo, and in human PMN; 3) the effect
      of Candida exposure on the ability of murine PMN to affect CD4+ Th1 cell
      proliferation and cytokine production; and 4) the mechanism responsible for this
      effect. Murine PMN constitutively expressed CD80 molecules on both the surface
      and intracellularly; however, in both murine and human PMN, CD80 expression was
      differentially modulated upon interaction with Candida yeasts or hyphae in vitro
      as well as in infected mice. The expression of the CD86 molecule was neither
      constitutive nor inducible upon exposure to the fungus. In vitro, Gr-1+ PMN were
      found to inhibit the activation of IFN-gamma-producing CD4+ T cells and to induce
      apoptosis through a CD80/CD28-dependent mechanism. A population of CD80+Gr-1+
      myeloid cells was found to be expanded in conventional as well as in bone marrow
      transplanted mice with disseminated candidiasis, but its depletion increased the
      IFN-gamma-mediated antifungal resistance. These data indicate that alternatively
      activated PMN expressing CD80 may adversely affect Th1-dependent resistance in
      fungal infections.

PMID- 12218137
TI  - Differential kinetics of antigen-specific CD4+ and CD8+ T cell responses in the
      regression of retrovirus-induced sarcomas.
AB  - Despite the accepted role for CD4+ T cells in immune control, little is known
      about the development of Ag-specific CD4+ T cell immunity upon primary infection.
      Here we use MHC class II tetramer technology to directly visualize the Ag
      specific CD4+ T cell response upon infection of mice with Moloney murine sarcoma
      and leukemia virus complex (MoMSV). Significant numbers of Ag-specific CD4+ T
      cells are detected both in lymphoid organs and in retrovirus-induced lesions
      early during infection, and they express the 1B11-reactive activation-induced
      isoform of CD43 that was recently shown to define effector CD8+ T cell
      populations. Comparison of the kinetics of the MoMSV-specific CD4+ and CD8+ T
      cell responses reveals a pronounced shift toward CD8+ T cell immunity at the site
      of MoMSV infection during progression of the immune response. Consistent with an
      important early role of Ag-specific CD4+ T cell immunity during MoMSV infection,
      CD4+ T cells contribute to the generation of virus-specific CD8+ T cell immunity
      within the lymphoid organs and are required to promote an inflammatory
      environment within the virus-infected tissue.

PMID- 12218138
TI  - Age-dependent cellular immune responses to Plasmodium vivax Duffy binding protein
      in humans.
AB  - The Plasmodium vivax merozoite Duffy binding protein (DBP) contains a cysteine
      rich region II (DBPII) that binds to the Duffy Ag receptor for chemokines on
      erythrocytes, which is essential for parasite invasion. Cellular immune responses
      to DBPII have not been reported in P. vivax endemic populations, although they
      may contribute to partial acquired immunity. To examine host cellular immunity to
      DBPII and identify major T cell epitopes, PBMCs from 107 individuals (2-68 years
      old) were examined for cytokine production by ELISPOT and/or ELISA to rDBP and
      overlapping peptides (displaced by 2 aa spanning a 170-aa region of DBPII
      corresponding to the critical binding motif to the Duffy Ag receptor for
      chemokines). In P. vivax-exposed subjects, 60 and 71% generated significant rDBP
      induced IFN-gamma and IL-10 production, respectively, 11% stimulated IL-2, and IL
      5 and IL-13 were not detected. Children <5 years of age had reduced levels and
      frequency of rDBP-induced IL-10 and IFN-gamma production compared with partially
      immune older children and adults (p < 0.01). Five major T cell epitopes were
      identified. Three of these T cell epitopes contained polymorphic residues present
      in the population. Peptides synthesized corresponding to these variants induced
      IFN-gamma and IL-10 production to one variant and little response to the other
      variant in the same individual. These results demonstrate age-dependent and
      variant-specific cellular immune responses to DBPII and implicate this molecule
      in partial acquired immunity to P. vivax in endemic populations.

PMID- 12218139
TI  - Vaccination with recombinant alphavirus or immune-stimulating complex antigen
      against respiratory syncytial virus.
AB  - Respiratory syncytial virus (RSV) causes severe respiratory diseases in infants
      and young children. Inappropriate immunity to the virus can lead to disease
      enhancement upon subsequent infection. In this study, we have characterized the
      antiviral immunity elicited by the recombinant Semliki Forest virus (SFV)
      encoding the RSV fusion (F) and attachment (G) protein, and compared with that
      induced by the immune-stimulating complex (ISCOM)-incorporated FG proteins.
      Antiviral immunity against RSV elicited nasally or parentally by either of the
      immunogen having divergent profiles could reduce lung RSV titers upon challenge.
      However, resistance to RSV without disease enhancement was only observed in those
      vaccinated with SFV recombinants via nasal route. Presence of postvaccination
      pulmonary IFN-gamma response to the H-2K(d)-restricted T cell epitope (F(85-93);
      KYKNAVTEL) was found to be associated with absence of enhanced pulmonary disease
      and goblet cell hyperplasia as well as reduced Th2-cytokine expression. This
      result demonstrates that the SFV recombinants can result in enhanced clearance of
      RSV without enhancing the RSV-associated disease, and underlines the importance
      in priming pulmonary MHC class I-restricted T cells when RSV FG-based vaccines
      are used.

PMID- 12218140
TI  - A C-reactive protein mutant that does not bind to phosphocholine and pneumococcal
      C-polysaccharide.
AB  - C-reactive protein (CRP), the major human acute-phase plasma protein, binds to
      phosphocholine (PCh) residues present in pneumococcal C-polysaccharide (PnC) of
      Streptococcus pneumoniae and to PCh exposed on damaged and apoptotic cells. CRP
      also binds, in a PCh-inhibitable manner, to ligands that do not contain PCh, such
      as fibronectin (Fn). Crystallographic data on CRP-PCh complexes indicate that
      Phe(66) and Glu(81) contribute to the formation of the PCh binding site of CRP.
      We used site-directed mutagenesis to analyze the contribution of Phe(66) and
      Glu(81) to the binding of CRP to PCh, and to generate a CRP mutant that does not
      bind to PCh-containing ligands. Five CRP mutants, F66A, F66Y, E81A, E81K, and
      F66A/E81A, were constructed, expressed in COS cells, purified, and characterized
      for their binding to PnC, PCh-BSA, and Fn. Wild-type and F66Y CRP bound to PnC
      with similar avidities, while binding of E81A and E81K mutants to PnC was
      substantially reduced. The F66A and F66A/E81A mutants did not bind to PnC.
      Identical results were obtained with PCh-BSA. In contrast, all five CRP mutants
      bound to Fn as well as did wild-type CRP. We conclude that Phe(66) is the major
      determinant of CRP-PCh interaction and is critical for binding of CRP to PnC. The
      data also suggest that the binding sites for PCh and Fn on CRP are distinct. A
      CRP mutant incapable of binding to PCh provides a tool to assess PCh-inhibitable
      interactions of CRP with its other biologically significant ligands, and to
      further investigate the functions of CRP in host defense and inflammation.

PMID- 12218141
TI  - Complement-induced impairment of innate immunity during sepsis.
AB  - This study defines the molecular basis for defects in innate immunity involving
      neutrophils during cecal ligation/puncture (CLP)-induced sepsis in rats. Blood
      neutrophils from CLP rats demonstrated defective phagocytosis and defective
      assembly of NADPH oxidase, the latter being due to the inability of p47(phox) to
      translocate from the cytosol to the cell membrane of neutrophils after cell
      stimulation by phorbol ester (PMA). The appearance of these defects was prevented
      by in vivo blockade of C5a in CLP rats. In vitro exposure of neutrophils to C5a
      led to reduced surface expression of C5aR and defective assembly of NADPH
      oxidase, as defined by failure in phosphorylation of p47(phox) and its
      translocation to the cell membrane, together with failure in phosphorylation of
      p42/p44 mitogen-activated protein kinases. These data identify a molecular basis
      for defective innate immunity involving neutrophils during sepsis.

PMID- 12218142
TI  - The early IL-4 response to Leishmania major and the resulting Th2 cell maturation
      steering progressive disease in BALB/c mice are subject to the control of
      regulatory CD4+CD25+ T cells.
AB  - Susceptibility and development of Th2 cells in BALB/c mice infected with
      Leishmania major result from early IL-4 production by Vbeta4Valpha8 CD4+ T cells
      in response to the Leishmania homolog of mammalian RACK1 Ag. A role for CD4+CD25+
      regulatory T cells in the control of this early IL-4 production was investigated
      by depleting in vivo this regulatory T cell population. Depletion induced an
      increase in the early burst of IL-4 mRNA in the draining lymph nodes of BALB/c
      mice, and exacerbated the course of disease with higher levels of IL-4 mRNA and
      protein in their lymph nodes. We further showed that transfer of 10(7) BALB/c
      spleen cells that were depleted of CD4+CD25+ regulatory T cells rendered SCID
      mice susceptible to infection and allowed Th2 differentiation while SCID mice
      reconstituted with 10(7) control BALB/c spleen cells were resistant to infection
      with L. major and developed a Th1 response. Treatment with a mAb against IL-4
      upon infection with L. major in SCID mice reconstituted with CD25-depleted spleen
      cells prevented the development of Th2 polarization and rendered them resistant
      to infection. These results demonstrate that CD4+CD25+ regulatory T cells play a
      role in regulating the early IL-4 mRNA and the subsequent development of a Th2
      response in this model of infection.

PMID- 12218143
TI  - Human papillomavirus virus-like particles do not activate Langerhans cells: a
      possible immune escape mechanism used by human papillomaviruses.
AB  - High-risk human papillomaviruses are linked to several malignancies including
      cervical cancer. Because human papillomavirus-infected women do not always mount
      protective antiviral immunity, we explored the interaction of human
      papillomavirus with Langerhans cells, which would be the first APCs the virus
      comes into contact with during infection. We determined that dendritic cells,
      normally targeted by vaccination procedures and Langerhans cells, normally
      targeted by the natural virus equally internalize human papillomavirus virus-like
      particles. However, in contrast to dendritic cells, Langerhans cells are not
      activated by human papillomavirus virus-like particles, illustrated by the lack
      of: up-regulating activation markers, secreting IL-12, stimulating T cells in an
      MLR, inducing human papillomavirus-specific immunity, and migrating from
      epidermal tissue. Langerhans cells, like dendritic cells, can display all of
      these characteristics when stimulated by proinflammatory agents. These data may
      define an intriguing immune escape mechanism used by human papillomavirus and
      form the basis for designing optimal vaccination strategies.

PMID- 12218144
TI  - Syntaxins 13 and 7 function at distinct steps during phagocytosis.
AB  - The phagosome is a dynamic organelle that undergoes progressive changes to
      acquire the machinery required to kill and degrade internalized foreign
      particles. This maturation process involves sequential interaction of newly
      formed phagosomes with several components of the endocytic pathway. The proteins
      that mediate the ordered fusion of endosomes and lysosomes with the phagosome are
      not known. In this study, we investigated the possible role of syntaxins present
      in the endo/lysosomal pathway in directing phagosomal maturation. We show that in
      phagocytic cells syntaxin 13 is localized to the recycling endosome compartment,
      while syntaxin 7 is found in late endosomes/lysosomes. Both proteins are
      recruited to the phagosome, but syntaxin 13 is acquired earlier and rapidly
      recycles off the phagosome, while syntaxin 7 is recruited later and continues to
      accumulate throughout the maturation process. Overexpression of truncated
      (cytosolic) forms of syntaxin 13 or 7 had no effect on phagocytosis, but exerted
      an inhibitory effect on phagosomal maturation. These results indicate that
      syntaxins 13 and 7 are both required for interaction of endosomes and/or
      lysosomes with the phagosome, but play distinct roles in the maturation process.

PMID- 12218145
TI  - NK cell activity during human cytomegalovirus infection is dominated by US2-11
      mediated HLA class I down-regulation.
AB  - A highly attractive approach to investigate the influence and hierarchical
      organization of viral proteins on cellular immune responses is to employ mutant
      viruses carrying deletions of various virus-encoded, immune-modulating genes.
      Here, we introduce a novel set of deletion mutants of the human CMV (HCMV)
      lacking the UL40 region either alone or on the background of a deletion mutant
      devoid of the entire US2-11 region. Deletion of UL40 had no significant effect on
      lysis of infected cells by NK cells, indicating that the expected enhancement of
      HLA-E expression by specific peptides derived from HCMV-encoded gpUL40 leader
      sequences was insufficient to confer target cell protection. Moreover, the
      kinetics of MHC class I down-regulation by US2-11 genes observed at early and
      late phases postinfection with wild-type virus correlated with increased
      susceptibility to NK lysis. Thus, the influence of HCMV genes on NK reactivity
      follows a hierarchy dominated by the US2-11 region, which encodes all viral genes
      capable of down-modulating expression of classical and non-classical MHC class I
      molecules. The insights gained from studies of such virus mutants may impact on
      future therapeutic strategies and vaccine development and incorporate NK cells in
      the line of defense mechanisms against HCMV infection.

PMID- 12218146
TI  - Surfactant protein D binds selectively to Klebsiella pneumoniae
      lipopolysaccharides containing mannose-rich O-antigens.
AB  - Surfactant protein D (SP-D) plays important roles in the regulation of innate
      immune responses in the lung. We have previously shown that SP-D can agglutinate
      and enhance the macrophage-dependent killing of specific unencapsulated phase
      variants of Klebsiella pneumoniae. In the present studies, we used 16 clinical
      isolates of Klebsiella representing four O-serotypes and examined the interaction
      of SP-D with their isolated LPSs. Although SP-D bound to the core oligosaccharide
      of rough LPS from all isolates, it selectively bound to smooth forms of LPS
      expressed by O-serotypes with mannose-rich repeating units in their O
      polysaccharides. SP-D was more potent in agglutinating unencapsulated phase
      variants of O-serotypes expressing these SP-D "reactive" O-polysaccharides, and
      more effectively inhibited the adhesion of these serotypes to lung epithelial
      cells. This novel anti-adhesion activity required the multimerization of trimeric
      SP-D subunits (dodecamers). Klebsiella serotypes expressing "nonreactive" LPS O
      Ags were isolated at a significantly higher frequency from patients with K.
      pneumoniae. Our findings suggest that SP-D plays important roles in the clearance
      of opportunistic Gram-negative bacteria and contributes to known serotypic
      differences in the pathogenicity of Klebsiella through specific interactions with
      O-polysaccharides.

PMID- 12218147
TI  - Induction of CD8+ T lymphocytes by Salmonella typhimurium is independent of
      Salmonella pathogenicity island 1-mediated host cell death.
AB  - Salmonella are intracellular bacterial pathogens that reside and replicate inside
      macrophages, and attenuated strains of Salmonella typhimurium can be used to
      deliver heterologous Ags for MHC class I and/or MHC class II-restricted
      presentation. Recently, it was shown that invasion of macrophages by S.
      typhimurium may result in the death of host macrophages via a mechanism harboring
      features of apoptotic and necrotic cell death. However, it is unknown whether
      this bacterial-induced host cell death affects immunity. In addition, it has been
      hypothesized that macrophage death following infection with S. typhimurium and
      subsequent uptake of apoptotic cells by APC are fundamental to the induction of
      CTL responses. In this study we investigated the in vivo induction of Ag-specific
      CD8+ T lymphocyte responses and compared CD8+ T lymphocyte responses elicited
      with S. typhimurium strains carrying a mutation in their invA gene, and therefore
      an inability to induce Salmonella pathogenicity island 1 (SPI-1)-mediated
      macrophage death, with responses elicited by an attenuated deltaaroAD strain. Ag
      specific CD8+ T lymphocyte responses were analyzed using IFN-gamma ELISPOT,
      tetramer binding, and in vivo and in vitro CTL assays. Our results showed that
      deltaaroAD and deltaaroADdeltainvA induced comparable levels of Ag-specific CD8+
      T lymphocyte responses as well as protective, Ag-specific B and CD4+ T lymphocyte
      immunity. Furthermore, experiments in macrophage-depleted mice showed that CD8+ T
      lymphocyte responses were effectively induced in the absence of macrophages.
      Together, our results imply that in this infection model, SPI-1-mediated cell
      death does not affect the immunological defense response and is not important for
      the induction of CD8+ T lymphocyte responses.

PMID- 12218148
TI  - An enteric helminth infection protects against an allergic response to dietary
      antigen.
AB  - Although helminths induce a polarized Th2 response they have been shown, in
      clinical studies, to confer protection against allergies. To elucidate the basis
      for this paradox, we have examined the influence of an enteric helminth infection
      on a model of food allergy. Upon Ag challenge, mice fed peanut (PN) extract plus
      the mucosal adjuvant cholera toxin (CT) produced PN-specific IgE that correlated
      with systemic anaphylactic symptoms and elevated plasma histamine. PN-specific
      IgE was not induced in helminth-infected mice fed PN without CT. Moreover, when
      PN plus CT was fed to helminth-infected mice, both PN-specific IgE and
      anaphylactic symptoms were greatly diminished. The down-regulation of PN-specific
      IgE was associated with a marked reduction in the secretion of IL-13 by PN
      specific T cells. When helminth-infected PN plus CT-sensitized mice were treated
      with neutralizing Abs to IL-10, the PN-specific IgE response and anaphylactic
      symptoms were similar to, or greater than, those seen in mice that receive PN and
      CT alone. Taken together, these results suggest that helminth-dependent
      protection against allergic disease involves immunoregulatory mechanisms that
      block production of allergen-specific IgE.

PMID- 12218149
TI  - Enhanced type 1 immunity after secondary viral challenge in mice primed as
      neonates.
AB  - The goal of infant immunization against viral infection is to develop protective
      long term memory responses. Priming neonatal mice with a low dose of Cas-Br-E
      murine leukemia virus (Cas) results in adult-like, type 1 protective responses.
      However, other studies suggest that Ag priming of neonates leads to an increase
      in type 2 secondary responses even when primary responses were type 1. We
      assessed whether type 1 CD8+ T cell-mediated responses developed in murine
      neonates are maintained after secondary challenge with Cas in adulthood. Despite
      the induction of significant anti-viral CD8+-mediated cytotoxic T lymphocyte and
      IFN-gamma responses, initial neonatal priming led to a lower frequency of virus
      specific T cells compared with adult priming. Adult frequencies were reached in
      mice primed as neonates only after secondary challenge in adulthood. A
      nonspecific and transient CD4+-mediated IL-4 response was present in all groups
      after secondary challenge with Cas or medium, indicating that this rise in type 2
      cytokine production was not unique to mice that had been primed as neonates.
      Rather, type 1 anti-viral memory CD8+ T cell responses developed in neonatal mice
      are stable, protective, and enhanced after secondary challenge.

PMID- 12218150
TI  - Opsonization of HIV-1 by semen complement enhances infection of human epithelial
      cells.
AB  - In the present study we demonstrate that both X4- and R5-tropic HIV-1 strains are
      able to infect the human epithelial cell line HT-29. Infection was enhanced 2
      fold when HIV was added to semen before contact with the cell cultures. The
      enhancing effect of semen was complement dependent, as evidenced by blockage of
      generation of C3a/C3a(desArg) in semen by heat or EDTA treatment of semen and
      suppression of semen-dependent enhancement with mAbs directed to complement
      receptor type 3 (CD11b/CD18) and soluble CD16. Infection of HT-29 cells was
      assessed by the release of p24 Ag in cultures and semiquantitative PCR of the HIV
      1 pol gene. Inhibition of infection of HT-29 by stromal cell-derived factor 1 was
      decreased in the case of semen-opsonized X4- and R5-tropic virus compared with
      unopsonized virus. In contrast, inhibition of infection by RANTES was increased
      for opsonized X4-tropic HIV-1 compared with unopsonized virus. Taken together
      these observations indicate that activation of complement in semen may play an
      enhancing role in mucosal transmission of HIV-1 by facilitating infection of
      epithelial cells and/or enhancing infection of complement receptor-expressing
      target cells in the mucosa.

PMID- 12218151
TI  - HIV-1 transcription and virus production are both accentuated by the
      proinflammatory myeloid-related proteins in human CD4+ T lymphocytes.
AB  - S100A8, S100A9, and S100A12, collectively known as myeloid-related proteins
      (MRPs), are highly expressed by the myeloid cell lineage and are found in the
      extracellular milieu during infections and inflammatory conditions. Recent data
      showed high levels of MRPs in the serum of HIV type 1 (HIV-1)-infected patients
      which correlated with disease progression and low CD4(+) counts. Therefore, we
      set out to investigate the effect of MRPs on HIV-1 replication. We observed a 4-
      to 5-fold induction of virus production in J1.1, a human T lymphoid cell line
      latently infected with HIV-1, following treatment with MRPs. Using luciferase
      based reporter gene assays, we demonstrated that MRPs induce a dose- and time
      dependent activation of the HIV-1 long terminal repeat promoter region that could
      be blocked by specific anti-MRP polyclonal Abs and by physical denaturation of
      these proteins. The MRP-mediated induction was acting through the HIV-1 enhancer
      sequence and was dependent upon NF-kappaB activity. These latter results were
      also confirmed by EMSA experiments conducted in Jurkat cells and freshly isolated
      PBMCs. In conclusion, we demonstrate that MRPs induce HIV-1 transcriptional
      activity and viral replication in infected CD4(+) T-lymphocytes at concentrations
      similar to those found in the serum of HIV-1-infected patients.

PMID- 12218152
TI  - Adoptive immunotherapy of advanced tumors with CD62 L-selectin(low) tumor
      sensitized T lymphocytes following ex vivo hyperexpansion.
AB  - Tumor-draining lymph nodes (TDLN) contain sensitized T cells with the phenotype
      CD62 L-selectin(low) (CD62L(low)) that can be activated ex vivo with anti-CD3 mAb
      and IL-2 to acquire potent dose-dependent effector function manifested upon
      adoptive transfer to secondary tumor-bearing hosts. In this study advanced tumor
      models were used as a stringent comparison of efficacy for the CD62L(low) subset,
      comprising 5-7% of the TDLN cells, vs the total population of TDLN cells
      following culture in high dose IL-2 (100 U/ml). During the 9-day activation
      period the total number of CD8+ T cells increased 1500-fold, with equivalent
      proliferation in the CD62L(low) vs the total TDLN cell cultures. Adoptive
      transfer of activated CD62L(low) cells eliminated 14-day pulmonary metastases and
      cured 10-day s.c. tumors, whereas transfer of maximally tolerated numbers of
      total TDLN cells was not therapeutic. Despite their propagation in a high
      concentration of IL-2, the hyperexpanded CD62L(low) subset of TDLN cells
      functioned in vivo without exogenous IL-2, and CD8+ T cells demonstrated relative
      helper independence. Moreover, the anti-tumor response was specific for the
      sensitizing tumor, and long term memory was established. The facile enrichment of
      tumor-reactive TDLN T cells, based on the CD62L(low) phenotype, circumvents the
      need for prior knowledge of the relevant tumor Ags. Coupling the isolation of pre
      effector T cells with rapid ex vivo expansion to >3 logs could overcome some of
      the shortcomings of active immunotherapy or in vivo cytokine treatment, where
      selective robust expansion of effector cells has been difficult to achieve.

PMID- 12218153
TI  - Activation of monocytic cells through Fc gamma receptors induces the expression
      of macrophage-inflammatory protein (MIP)-1 alpha, MIP-1 beta, and RANTES.
AB  - Monocytic cells were stimulated with IgG-OVA equivalence immune complexes, mAb
      reacting with FcgammaRI, FcgammaRIIA, and FcgammaRIII, LPS, TNF-alpha, and the
      combination of ionomycin and phorbol ester, to address their effects on the
      expression of the mRNAs encoding for chemokines. Stimulation of monocytes with
      immune complexes induced a rapid expression of macrophage-inflammatory protein
      (MIP)-1alpha, MIP-1beta, and IL-8 mRNAs. In contrast, RANTES mRNA was already
      detectable in resting cells and only increased after 16 h of stimulation. A
      similar pattern was observed following homotypic stimulation of FcgammaR with mAb
      reacting with FcgammaRI and FcgammaRIIA, but not with a mAb reacting with
      FcgammaRIII, a subtype of receptor not expressed in THP-1 cells, thus indicating
      that both FcgammaRI and FcgammaRIIA are involved in the response. The pattern of
      chemokine induction elicited by LPS and the combination of ionomycin and PMA
      showed some similarities to those produced by FcgammaR cross-linking, although
      expression of IFN-gamma-inducible protein 10 mRNA was also observed in response
      to those agonists. The production of MIP-1alpha, MIP-1beta, and RANTES proteins
      encompassing the induction of their mRNAs was confirmed by specific ELISA.
      Experiments to address the transcription factors involved in the regulation of
      MIP-1alpha using pharmacological agents and EMSA showed the possible involvement
      of CCAAT/enhancer-binding protein beta sites and ruled out the functional
      significance of both NF-AT and AP-1 sites.

PMID- 12218154
TI  - Suppression of monocyte chemoattractant protein 1, but not IL-8, by alprazolam:
      effect of alprazolam on c-Rel/p65 and c-Rel/p50 binding to the monocyte
      chemoattractant protein 1 promoter region.
AB  - Alprazolam is a hypnotic/tranquilizer that has been shown to specifically inhibit
      the platelet-activating factor (PAF)-induced aggregation of human platelets. The
      goal of this study was to elucidate whether alprazolam modulates IL-1alpha
      initiated responses. For this purpose we investigated the effects of alprazolam
      on the IL-1alpha-induced production of inflammatory cytokines (IL-8 and monocyte
      chemoattractant protein 1 (MCP-1)) in a human glioblastoma cell line, T98G, and
      explored the signaling pathways involved. We found that alprazolam inhibited IL
      1alpha-elicited MCP-1 production within a range of 0.1-3 micro M. In contrast, it
      did not inhibit IL-1alpha-induced IL-8 production. Although NF-kappaB is involved
      in regulating the IL-1alpha-induced expression of MCP-1 and IL-8, the degradation
      of IkappaB-alpha stimulated by IL-1alpha was not inhibited by alprazolam.
      Alprazolam prevented NF-kappaB from binding to the MCP-1 promoter region (the A2
      and A1 oligonucleotide probes), but binding of NF-kappaB to IL-8/NF-kappaB was
      not inhibited. Moreover, alprazolam inhibited c-Rel/p50 binding to the A2
      oligonucleotide probe, but not p50/p65 from binding to the IL-8/NF-kappaB site.
      While AP-1 is involved in regulating the IL-1alpha-induced expression of IL-8,
      but not MCP-1, alprazolam potentiated the binding of c-Jun/c-Fos to the AP-1
      oligonucleotide probe. These results show that the inhibition of IL-1alpha
      mediated MCP-1 production by alprazolam is mainly due to inhibition of c-Rel/p65
      and c-Rel/p50 binding to the MCP-1 promoter region, since alprazolam did not
      affect the IL-1alpha-mediated activation of NF-kappaB (p50/p65) or AP-1 (c-Jun/c
      Fos) binding to the IL-8 promoter region. In conclusion, a new action of
      alprazolam was elucidated, as shown in the inhibition of c-Rel/p65- and c-Rel/p50
      regulated transcription.

PMID- 12218155
TI  - Regulation of phosphatidylinositol 3-kinase activity and phosphatidylinositol
      3,4,5-trisphosphate accumulation by neutrophil priming agents.
AB  - Neutrophil priming by agents such as TNF-alpha and GM-CSF causes a dramatic
      increase in the response of these cells to secretagogue agonists and affects the
      capacity of neutrophils to induce tissue injury. In view of the central role of
      phosphatidylinositol 3-kinase (PI3-kinase) in regulating NADPH oxidase activity
      we examined the influence of priming agents on agonist-stimulated
      phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) accumulation in human
      neutrophils. Pretreatment of neutrophils with TNF-alpha or GM-CSF, while not
      influencing fMLP-stimulated PtdIns(3,4,5)P3 accumulation at 5 s, caused a major
      increase in PtdIns(3,4,5)P3 at later times (10-60 s), which paralleled the
      augmented superoxide anion (O2-) response. The intimate relationship between
      PtdIns(3,4,5)P3 accumulation and O2- release was confirmed using platelet
      activating factor, which caused full but transient priming of both responses.
      Likewise, LY294002, a PI3-kinase inhibitor, and genistein, a tyrosine kinase
      inhibitor, caused parallel inhibition of O2- generation and PtdIns(3,4,5)P3
      accumulation; in contrast, radicicol, which inhibits receptor-mediated activation
      of p85 PI3-kinase, had no effect on either response. Despite major increases in
      PI3-kinase activity observed in p85 and anti-phosphotyrosine immunoprecipitates
      in growth factor-stimulated smooth muscle cells, no such increase was observed in
      primed/stimulated neutrophils. In contrast, both fMLP and TNF-alpha alone caused
      a 3-fold increase in PI3-kinase activity in p110gamma PI3-kinase
      immunoprecipitates. p21(ras) activation (an upstream regulator of PI3-kinase) was
      unaffected by priming. These data demonstrate that timing and magnitude of
      PtdIns(3,4,5)P3 accumulation in neutrophils correlate closely with O2-
      generation, that PI3-kinase-gamma is responsible for the enhanced PtdIns(3,4,5)P3
      production seen in primed cells, and that factors other than activation of
      p21(ras) underlie this response.

PMID- 12218156
TI  - IL-4 and IL-12 regulate proteoglycan-induced arthritis through Stat-dependent
      mechanisms.
AB  - IL-4, a well-recognized modulator of macrophage activation, is perceived as an
      anti-inflammatory cytokine; however, under certain circumstances IL-4 may
      function as a proinflammatory cytokine. We have previously demonstrated that IL-4
      treatment of mice with proteoglycan-induced arthritis (PGIA) inhibited the
      development of disease. To determine whether the capacity of IL-4 to inhibit
      disease is dependent on IL-4-mediated regulation of IL-12, we assessed the
      requirement for IL-4 in modulating development of PGIA. Immunization of mice,
      lacking IL-4 and Stat6, with proteoglycan results in a significant increase in
      arthritis severity in comparison to wild-type controls, suggesting that arthritis
      severity is regulated by IL-4 through a Stat6-dependent mechanism. Concomitant
      with exacerbated disease in IL-4(-/-) mice, there is a significant increase in
      the systemic production of proinflammatory cytokines IL-12, TNF-alpha, and IFN
      gamma and in levels of mRNA transcripts for proinflammatory cytokines and
      chemokines in joints. Disease is suppressed in Stat4(-/-) mice indicating that
      elevated levels of IL-12 contribute to exacerbation of arthritis and that
      suppression is accompanied by reduced levels of IFN-gamma production. In support
      of this, IFN-gamma(-/-) mice are protected from PGIA and the degree of
      inflammation is similar to Stat4(-/-) mice. The decrease in disease severity in
      IFN-gamma(-/-) and Stat4(-/-) mice correlates with diminished TNF-alpha levels
      but there is no switch to a Th2-type response. Taken together, these results
      suggest that IL-4 regulates the severity of disease in PGIA by controlling IL-12
      production, which in turn regulates the magnitude of IFN-gamma expression through
      a Stat4-dependent pathway.

PMID- 12218157
TI  - IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and
      regulate the expression of receptor activator of NF-kappa B ligand,
      osteoprotegerin, and receptor activator of NF-kappa B in mouse calvariae.
AB  - IL-6, leukemia inhibitory factor (LIF), and oncostatin M (OSM) are IL-6-type
      cytokines that stimulate osteoclast formation and function. In the present study,
      the resorptive effects of these agents and their regulation of receptor activator
      of NF-kappaB ligand (RANKL), RANK, and osteoprotegerin (OPG) were studied in
      neonatal mouse calvaria. When tested separately, neither human (h) IL-6 nor the
      human soluble IL-6R (shIL-6R) stimulated bone resorption, but when hIL-6 and the
      shIL-6R were combined, significant stimulation of both mineral and matrix release
      from bone explants was noted. Semiquantitative RT-PCR showed that hIL-6 plus shIL
      6R enhanced the expression of RANKL and OPG in calvarial bones, but decreased
      RANK expression. Human LIF, hOSM, and mouse OSM (mOSM) also stimulated 45Ca
      release and enhanced the mRNA expression of RANKL and OPG in mouse calvaria, but
      had no effect on the expression of RANK. In agreement with the RT-PCR analyses,
      ELISA measurements showed that both hIL-6 plus shIL-6R and mOSM increased RANKL
      and OPG proteins. 1,25-Dihydroxyvitamin D3 (D3) also increased the RANKL protein
      level, but decreased the protein level of OPG. OPG inhibited 45Ca release
      stimulated by RANKL, hIL-6 plus shIL-6R, hLIF, hOSM, mOSM, and D3. An Ab
      neutralizing mouse gp130 inhibited 45Ca release induced by hIL-6 plus shIL-6R.
      These experiments demonstrated stimulation of calvarial bone resorption and
      regulation of mRNA and protein expression of RANKL and OPG by D3 and IL-6 family
      cytokines as well as regulation of RANK expression in preosteoclasts/osteoclasts
      of mouse calvaria by D3 and hIL-6 plus shIL-6R.

PMID- 12218158
TI  - Identification, cloning, and functional characterization of a murine lipoxin A4
      receptor homologue gene.
AB  - To identify additional members of the murine N-formyl-Met-Leu-Phe peptide
      receptor family (fMLF-R), a mouse macrophage cDNA library was screened using the
      open reading frame of murine N-formyl peptide receptor. Four individual
      hybridizing cDNA clones were maintained through tertiary screening. One cDNA
      clone was a truncated, polyadenylated version of the previously described murine
      fMLF-R. The other three cDNA clones varied in length, but contained identical
      open reading frame sequences. One clone, 8C10, was selected for further study and
      shared 70% sequence identity with murine-fMLF-R and 89% sequence identity with
      murine lipoxin A4 receptor cDNA. When placed into the pcDNA-3 expression vector
      and cotransfected with Galpha16 cDNA into COS-1 cells, 8C10 cDNA induced the
      production of inositol-1,4,5-triphosphate when concentrations of 1-1600 nM
      lipoxin A4 (LXA4) were tested as ligands. Northern blot analysis of murine organs
      indicated that the 8C10 message is present in lung, spleen, and adipose tissue.
      Moreover, mice treated with LPS demonstrated increased expression of 8C10 message
      in spleen and adipose tissue, while showing a slight reduction in lung. We have
      also characterized the 8C10 structural gene from a 129Sv/J genomic library and
      have determined its size to be >6.1 kb in length and comprised of two exons
      separated by a 4.8-kb intron. Collectively, these data indicate that this
      homologue receptor is closely related to the murine LXA4 receptor and
      functionally responds to LXA4 as a ligand.

PMID- 12218159
TI  - Endotoxemia prevents the cerebral inflammatory wave induced by intraparenchymal
      lipopolysaccharide injection: role of glucocorticoids and CD14.
AB  - There is a robust and transient innate immune response in the brain during
      endotoxemia, which is associated with a cascade of NF-kappaB signaling events and
      transcriptional activation of genes that encode TNF-alpha and the LPS receptor
      CD14. The present study investigated whether circulating LPS has the ability to
      modulate the cerebral innate immune response caused by an intrastriatal (IS)
      injection of the endotoxin. We also tested the possibility that CD14 plays a role
      in these effects and male rats received an intracerebroventricular injection with
      an anti-CD14 before the IS LPS administration. The single LPS bolus into the
      striatum caused a strong and time-dependent transcriptional activation of TNF
      alpha, IkappaBalpha, CD14, and monocyte chemoattractant protein-1 mRNA in
      microglial cells ipsilateral to the site of injection. Surprisingly, this wave of
      induced transcripts was essentially abolished by the systemic endotoxin
      pretreatment. Such anti-inflammatory properties of circulating LPS are mediated
      via plasma corticosterone, because exogenous corticoids mimicked while
      glucocorticoid receptor antagonist RU486 prevented the effects of systemic
      endotoxin challenge. Of interest is the partial involvement of CD14 in LPS
      induced neuroinflammation; the anti-CD14 significantly abolished the microglial
      activity at day 3, but not at times earlier. The inflammatory response provoked
      by an acute intraparenchymal LPS bolus was not associated with convincing
      neurodegenerative processes. These data provide compelling evidence that systemic
      inflammation, through the increase in circulating glucocorticoids, has the
      ability to prevent the cerebral innate immune reaction triggered by an IS
      endotoxin injection. This study also further consolidates the existence of such
      system in the brain, which is finely regulated and its transient activation is
      not harmful for the neuronal elements.

PMID- 12218160
TI  - Marked prolongation of cardiac allograft survival by dendritic cells genetically
      engineered with NF-kappa B oligodeoxyribonucleotide decoys and adenoviral vectors
      encoding CTLA4-Ig.
AB  - Bone marrow-derived dendritic cells (DCs) can be genetically engineered using
      adenoviral (Ad) vectors to express immunosuppressive molecules that promote T
      cell unresponsiveness. The success of these DCs for therapy of allograft
      rejection has been limited in part by the potential of the adenovirus to promote
      DC maturation and the inherent ability of the DC to undergo maturation following
      in vivo administration. DC maturation occurs via NF-kappaB-dependent mechanisms,
      which can be blocked by double-stranded "decoy" oligodeoxyribonucleotides (ODNs)
      containing binding sites for NF-kappaB. Herein, we describe the combined use of
      NF-kappaB ODNs and rAd vectors encoding CTLA4-Ig (Ad CTLA4-Ig) to generate stably
      immature murine myeloid DCs that secrete the potent costimulation blocking agent.
      These Ad CTLA4-Ig-transduced ODN DCs exhibit markedly impaired allostimulatory
      ability and promote apoptosis of activated T cells. Furthermore, administration
      of Ad CTLA4-Ig ODN-treated donor DCs (C57BL10; B10(H-2b)) before transplant
      significantly prolongs MHC-mismatched (C3HHeJ; C3H(H-2k)) vascularized heart
      allograft survival, with long-term (>100 days) donor-specific graft survival in
      40% of recipients. The mechanism(s) responsible for DC tolerogenicity, which may
      involve activation-induced apoptosis of alloreactive T cells, do not lead to
      skewing of intragraft Th cytokine responses. Use of NF-kappaB antisense decoys in
      conjunction with rAd encoding a potent costimulation blocking agent offers
      promise for therapy of allograft rejection or autoimmune disease with
      minimization of systemic immunosuppression.

PMID- 12218161
TI  - Restriction of de novo pyrimidine biosynthesis inhibits Th1 cell activation and
      promotes Th2 cell differentiation.
AB  - Leflunomide, an inhibitor of de novo pyrimidine biosynthesis, has recently been
      introduced as a treatment for rheumatoid arthritis in an attempt to ameliorate
      inflammation by inhibiting lymphocyte activation. Although the immunosuppressive
      ability of leflunomide has been well described in several experimental animal
      models, the precise effects of a limited pyrimidine supply on T cell
      differentiation and effector functions have not been elucidated. We investigated
      the impact of restricted pyrimidine biosynthesis on the activation and
      differentiation of CD4 T cells in vivo and in vitro. Decreased activation of
      memory CD4 T cells in the presence of leflunomide resulted in impaired generation
      and outgrowth of Th1 effectors without an alteration of Th2 cell activation.
      Moreover, priming of naive T cells in the presence of leflunomide promoted Th2
      differentiation from uncommitted precursors in vitro and enhanced Th2 effector
      functions in vivo, as indicated by an increase in Ag-specific Th2 cells and in
      the Th2-dependent Ag-specific Ig responses (IgG1) in immunized mice. The effects
      of leflunomide on T cell proliferation and differentiation could be antagonized
      by exogenous UTP, suggesting that they were related to a profound inhibition of
      de novo pyrimidine biosynthesis. These results indicate that leflunomide might
      exert its anti-inflammatory activities in the treatment of autoimmune diseases by
      preventing the generation of proinflammatory Th1 effectors and promoting Th2 cell
      differentiation. Moreover, the results further suggest that differentiation of
      CD4 T cells can be regulated at the level of nucleotide biosynthesis.

PMID- 12218162
TI  - CD4 T cell depletion is linked directly to immune activation in the pathogenesis
      of HIV-1 and HIV-2 but only indirectly to the viral load.
AB  - The causal relationships among CD4 cell depletion, HIV replication, and immune
      activation are not well understood. HIV-2 infection, "nature's experiment" with
      inherently attenuated HIV disease, provides additional insights into this issue.
      We report the finding that in HIV-2 and HIV-1 patients with a comparable degree
      of CD4 depletion the imbalance in the relative sizes of the naive and memory T
      cell populations and the up-regulation of CD4 and CD8 cell activation markers
      (HLA-DR, CD38, CD69, Fas molecules) are similar, even though the viral load in
      the plasma of HIV-2-infected patients is two orders of magnitude lower than in
      HIV-1 patients and HIV-2 patients are known to have slower rates of CD4 T cell
      decline and a better clinical prognosis. Moreover, we found a similar increase in
      the frequency of cycling CD4 T cells (Ki67+), which was in strong correlation
      with the expression of activation markers. Finally, the level of T cell anergy,
      as assessed by the proliferative responses to CD3 stimulation and to a panel of
      microbial Ags, proved to be comparable in HIV-1 and HIV-2 patients with a similar
      degree of CD4 depletion despite large differences in viral load. Our data are
      consistent with a direct causal relationship between immune activation and CD4
      cell depletion in HIV disease and an only indirect relation of these parameters
      to the virus replication rate. Invoking the concept of proximal immune activation
      and virus transmission, which links efficient transmission of virus to local cell
      activation and proliferation in response to Ags and inflammation, we propose an
      integrative interpretation of the data and suggest that strongly elevated immune
      activation induces CD4 cell depletion and not vice versa, with potential
      implications for the choice of treatment strategies.

PMID- 12218163
TI  - TCR rearrangement in lymphocytes infiltrating melanoma metastases after
      administration of autologous dinitrophenyl-modified vaccine.
AB  - Administration of a vaccine consisting of autologous melanoma cells modified with
      a hapten, dinitrophenyl (DNP), induces T cell infiltration of metastatic sites.
      We have reported an analysis of these infiltrating T cells, indicating that
      certain TCR-Vbeta gene segments are greatly overexpressed. In this study, we
      investigate the rearrangement of the TCR-Vbeta as well as the junctional
      diversity in T cells infiltrating melanoma metastases following treatment with
      DNP vaccine. In 19 of 26 control specimens, V-D-J length analysis showed the
      expected polyclonal patterns. In contrast, postvaccine tumors from 9 of 10
      patients showed dominant peaks of V-D-J junction size in one or more Vbeta
      families. Dominant peaks were seen most frequently in six Vbeta families (Vbeta7,
      12, 13, 14, 16, and 23) and were never seen in seven others. Further analysis of
      the oligoclonal Vbeta products showed dominant peaks in the J region as well. Of
      particular interest was the finding that Vbeta and Jbeta peaks were similar in
      inflamed metastases obtained at different times or from different sites from the
      same patient. Although 6 of 10 patients expressed HLA-A1, there was no common
      pattern of TCR rearrangements among them. Finally, the amplified PCR products
      from seven of these specimens were cloned and sequenced and the amino acid
      sequence of the complementarity-determining region 3 was deduced. In six of seven
      specimens, the same complementarity-determining region 3 sequence was repeated in
      at least two clones and in five of seven in at least three clones. Our study
      indicates that DNP vaccine induces the expansion of particular T cell clones that
      may be agents of its antitumor effects.

PMID- 12218164
TI  - Identification of human autoantibodies to the DNA ligase IV/XRCC4 complex and
      mapping of an autoimmune epitope to a potential regulatory region.
AB  - The nonhomologous end-joining pathway is the principal mechanism for repair of
      ionizing radiation-induced, double-strand breaks in mammalian cells. Three
      polypeptides in this pathway, including the two subunits of Ku protein and the
      catalytic subunit of the DNA-dependent protein kinase, are known targets of
      autoantibodies in systemic rheumatic diseases. Here we show that two additional
      polypeptides in the pathway, DNA ligase IV and XRCC4, are also targets of
      autoantibodies. These Abs were present in 20% of patients with systemic lupus
      erythematosus and overlap syndrome. Previous work has shown that XRCC4 is subject
      to radiation-induced post-translational modification, including phosphorylation
      by DNA-dependent protein kinase and cleavage by caspase 3. We mapped a major
      autoimmune epitope in XRCC4 and found that it encompassed a DNA-dependent protein
      kinase phosphorylation site, which is located at serine 260; that it was adjacent
      to a site for caspase 3, which cleaves after residue 265; and that it also
      spanned a site for the inflammatory protease, granzyme B, which cleaves after
      residue 254. The finding that five different polypeptides in the nonhomologous
      end-joining pathway are potential targets of autoantibodies together with the
      observation that one of the autoimmune epitopes in XRCC4 coincides with a
      sequence that is a nexus for radiation-induced regulatory events suggest that
      exposure to agents that introduce DNA double-strand breaks may be one of the
      factors that influences the development of an autoimmune response in susceptible
      individuals.

PMID- 12218165
TI  - Inhibition of adjuvant arthritis by a DNA vaccine encoding human heat shock
      protein 60.
AB  - Adjuvant arthritis (AA) is an autoimmune disease inducible in rats involving T
      cell reactivity to the mycobacterial 65-kDa heat shock protein (HSP65). HSP65
      specific T cells cross-reactive with the mammalian 60-kDa heat shock protein
      (HSP60) are thought to participate in the modulation of AA. In this work we
      studied the effects on AA of DNA vaccination using constructs coding for HSP65
      (pHSP65) or human HSP60 (pHSP60). We found that both constructs could inhibit AA,
      but that pHSP60 was more effective than pHSP65. The immune effects associated
      with specific DNA-induced suppression of AA were complex and included enhanced T
      cell proliferation to a variety of disease-associated Ags. Effective vaccination
      with HSP60 or HSP65 DNA led paradoxically to up-regulation of IFN-gamma secretion
      to HSP60 and, concomitantly, to down-regulation of IFN-gamma secretion to the
      P180-188 epitope of HSP65. There were also variable changes in the profiles of IL
      10 secretion to different Ags. However, vaccination with pHSP60 or pHSP65
      enhanced the production of TGFbeta1 to both HSP60 and HSP65 epitopes. Our results
      support a regulatory role for HSP60 autoreactivity in AA and demonstrate that
      this control mechanism can be activated by DNA vaccination with both HSP60 or
      HSP65.

PMID- 12218166
TI  - T cell immunity in connective tissue disease patients targets the RNA binding
      domain of the U1-70kDa small nuclear ribonucleoprotein.
AB  - Although the T cell dependence of autoimmune responses in connective tissue
      diseases has been well established, limited information exists regarding the T
      cell targeting of self Ags in humans. To characterize the T cell response to a
      connective tissue disease-associated autoantigen, this study generated T cell
      clones from patients using a set of peptides encompassing the entire linear
      sequence of the 70-kDa subunit of U1 snRNP (U1-70kDa) small nuclear
      ribonucleoprotein. Despite the ability of U1-70kDa to undergo multiple forms of
      Ag modification that have been correlated with distinct clinical disease
      phenotypes, a remarkably limited and consistent pattern of T cell targeting of U1
      70kDa was observed. All tested T cell clones generated against U1-70kDa were
      specific for epitopes within the RNA binding domain (RBD) of the protein. High
      avidity binding of the RBD with U1-RNA was preserved with the disease-associated
      modified forms of U1-70kDa tested. The high avidity interaction between the U1
      RBD on the polypeptide and U1-RNA may be critical in immune targeting of this
      region in autoimmunity. The T cell autoimmune response to U1-70kDa appears to
      have less diversity than is seen in the humoral response; and therefore, may be a
      favorable target for therapeutic intervention.

PMID- 12218167
TI  - MHC class I alleles influence set-point viral load and survival time in simian
      immunodeficiency virus-infected rhesus monkeys.
AB  - In HIV-infected humans and SIV-infected rhesus macaques, host genes influence
      viral containment and hence the duration of the disease-free latency period. Our
      knowledge of the rhesus monkey immunogenetics, however, is limited. In this
      study, we describe partial cDNA sequences of five newly discovered rhesus macaque
      (Mamu) class I alleles and PCR-based typing techniques for the novel and
      previously published Mhc class I alleles. Using 15 primer pairs for PCR-based
      typing and DNA sequence analysis, we identified at least 21 Mhc class I alleles
      in a cohort of 91 SIV-infected macaques. The results confirm the presence of
      multiple class I genes in rhesus macaques. Of these alleles, Mamu-A*01 was
      significantly associated with lower set-point viral load and prolonged survival
      time. Mamu-A*1303 was associated with longer survival and a "novel" Mhc class I
      allele with lower set-point viral load. The alleles are frequent in rhesus
      macaques of Indian origin (12-22%). In addition, survival probability of
      individual SIV-infected rhesus monkeys increased with their number of alleles
      considered to be associated with longer survival. The results contribute to
      improve the interpretation and quality of preclinical studies in rhesus monkeys.

PMID- 12218168
TI  - Impaired effector function of hepatitis C virus-specific CD8+ T cells in chronic
      hepatitis C virus infection.
AB  - The cellular immune response contributes to clearance of hepatitis C virus (HCV)
      and persists for decades after recovery from infection. The immunological basis
      for the inefficiency of the cellular immune response in chronically infected
      persons is not known. Here, we used four HLA-A2 tetramers, specific for two HCV
      core and two HCV NS3 epitopes, to investigate at the single-cell level effector
      function and phenotype of HCV-specific CD8+ T cells in 20 chronically infected
      and 12 long-term recovered patients. Overall, HCV-specific, tetramer+ T cells
      were more frequently found in PBMCs of chronically infected patients than in
      those of recovered patients. However, when compared with HCV-tetramer+ T cells of
      recovered patients, they displayed an impaired proliferative capacity. As a
      result of the impaired proliferative capacity, HCV-specific T cell lines derived
      from chronically infected patients displayed less peptide-specific cytotoxicity
      than those from recovered patients. In addition, proliferation and ex vivo IFN
      gamma production of HCV-tetramer+ cells, but not influenza-virus-specific T
      cells, were defective in chronically infected patients and could not be restored
      by in vitro stimulation with peptide and IL-2. At least three distinct phenotypes
      of HCV-specific CD8+ T cells were identified and associated with certain
      functional characteristics. In addition, impairment of proliferative, cytokine,
      and cytotoxic effector functions of tetramer+ T cells in viremic patients was
      associated with weak ex vivo HCV-specific CD4+ T cell responses. Thus, the
      defective functions of HCV-specific CD8+ T cells might contribute to viral
      persistence in chronically infected patients, and knowledge on their
      reversibility may facilitate the development of immunotherapeutic vaccines.

PMID- 12218169
TI  - The skeletal muscle Ca2+ release channel has an oxidoreductase-like domain.
AB  - We used a combination of bioinformatics, electron cryomicroscopy, and biochemical
      techniques to identify an oxidoreductase-like domain in the skeletal muscle Ca2+
      release channel protein (RyR1). The initial prediction was derived from sequence
      based fold recognition for the N-terminal region (41-420) of RyR1. The putative
      domain was computationally localized to the clamp domain in the cytoplasmic
      region of a 22A structure of RyR1. This localization was subsequently confirmed
      by difference imaging with a sequence specific antibody. Consistent with the
      prediction of an oxidoreductase domain, RyR1 binds [3H]NAD+, supporting a model
      in which RyR1 has a oxidoreductase-like domain that could function as a type of
      redox sensor.

PMID- 12218170
TI  - Singularity in budding: a role for the evolutionarily conserved small GTPase
      Cdc42p.
AB  - The budding yeast Saccharomyces cerevisiae initiates polarized growth or budding
      once per cell cycle at a specific time of the cell cycle and at a specific
      location on the cell surface. Little is known about the molecular nature of the
      temporal and spatial regulatory mechanisms. It is also unclear what factors, if
      any, among the numerous proteins required to make a bud are involved in the
      determination of budding frequency. Here we describe a class of cdc42 mutants
      that produce multiple buds at random locations on the cell surface within one
      nuclear cycle. The critical mutation responsible for this phenotype affects amino
      acid residue 60, which is located in a domain required for GTP binding and
      hydrolysis. This mutation bypasses the requirement for the essential guanine
      nucleotide-exchange factor Cdc24p, suggesting that the alteration at residue 60
      makes Cdc42p hyperactive, which was confirmed biochemically. This result also
      suggests that the only essential function of Cdc24p is to activate Cdc42p.
      Together, these data suggest that the temporal and spatial regulation of
      polarized growth converges at the level of Cdc42p and that the activity of Cdc42p
      determines the budding frequency.

PMID- 12218171
TI  - Identification of a human telomerase reverse transcriptase peptide of low
      affinity for HLA A2.1 that induces cytotoxic T lymphocytes and mediates lysis of
      tumor cells.
AB  - Telomerase reverse transcriptase (TRT) is a tumor-associated antigen expressed in
      the vast majority of human tumors and is presently one of the most promising
      target candidates for a therapeutic cancer vaccine. TRT is also expressed at low
      level in selected tissues and should be considered a self antigen. In the present
      study we sought to develop cytotoxic T lymphocytes (CTL) responses directed
      against human (h)TRT peptides with low relative affinity for which the available
      repertoire is to be preferentially spared from tolerance. This was accomplished
      by using analogue peptides of hTRT whose relative affinity for the MHC was
      increased by a targeted (-->Tyr) substitution in position one. By immunizing HLA
      A2.1 transgenic mice with these analogue peptides, we identified one such low
      relative affinity peptide (p572) that is endogenously processed and presented by
      HLA A2.1 in tumor cells, and is recognized by specific CTL. We used the highly
      immunogenic analogue peptide to successfully induce TRT-specific CTL in cancer
      patients and normal donors. CTL against p572-lysed human and mouse tumor cells
      but not activated autologous B cells. This peptide represents, therefore, an
      important candidate component of a cancer vaccine based on a TRT substrate and
      validates the strategy of targeting peptides with low affinity for the MHC for
      cancer immunotherapy.

PMID- 12218172
TI  - Evolutionary analysis of Arabidopsis, cyanobacterial, and chloroplast genomes
      reveals plastid phylogeny and thousands of cyanobacterial genes in the nucleus.
AB  - Chloroplasts were once free-living cyanobacteria that became endosymbionts, but
      the genomes of contemporary plastids encode only approximately 5-10% as many
      genes as those of their free-living cousins, indicating that many genes were
      either lost from plastids or transferred to the nucleus during the course of
      plant evolution. Previous estimates have suggested that between 800 and perhaps
      as many as 2,000 genes in the Arabidopsis genome might come from cyanobacteria,
      but genome-wide phylogenetic surveys that could provide direct estimates of this
      number are lacking. We compared 24,990 proteins encoded in the Arabidopsis genome
      to the proteins from three cyanobacterial genomes, 16 other prokaryotic reference
      genomes, and yeast. Of 9,368 Arabidopsis proteins sufficiently conserved for
      primary sequence comparison, 866 detected homologues only among cyanobacteria and
      834 other branched with cyanobacterial homologues in phylogenetic trees.
      Extrapolating from these conserved proteins to the whole genome, the data suggest
      that approximately 4,500 of Arabidopsis protein-coding genes ( approximately 18%
      of the total) were acquired from the cyanobacterial ancestor of plastids. These
      proteins encompass all functional classes, and the majority of them are targeted
      to cell compartments other than the chloroplast. Analysis of 15 sequenced
      chloroplast genomes revealed 117 nuclear-encoded proteins that are also still
      present in at least one chloroplast genome. A phylogeny of chloroplast genomes
      inferred from 41 proteins and 8,303 amino acids sites indicates that at least two
      independent secondary endosymbiotic events have occurred involving red algae and
      that amino acid composition bias in chloroplast proteins strongly affects plastid
      genome phylogeny.

PMID- 12218173
TI  - A functional polymorphism in the promoter of the progesterone receptor gene
      associated with endometrial cancer risk.
AB  - Excessive estrogen stimulation unopposed by progesterone strongly predisposes to
      endometrial cancer. Because the antiproliferative effect of progesterone requires
      the progesterone receptor (PR), which exists in two isoforms, PR-A and -B, we
      reasoned that variants in the PR gene may predispose to endometrial cancer. We
      found six variable sites, including four polymorphisms in the hPR gene and five
      common haplotypes. One promoter region polymorphism, +331G/A, creates a unique
      transcription start site. Biochemical assays showed that the +331G/A polymorphism
      increases transcription of the PR gene, favoring production of hPR-B in an
      endometrial cancer cell line. Using a case-control study nested within the
      Nurses' Health Study cohort, we observed a statistically significant association
      between the +331G/A polymorphism and the risk of endometrial cancer, which was
      even greater in overweight women carriers. After including a second population of
      controls, these associations remained intact. Our findings suggest that the
      +331G/A hPR gene polymorphism may contribute to endometrial cancer risk by
      increasing expression of the hPR-B isoform.

PMID- 12218174
TI  - RecX protein abrogates ATP hydrolysis and strand exchange promoted by RecA:
      insights into negative regulation of homologous recombination.
AB  - In many eubacteria, coexpression of recX with recA is essential for attenuation
      of the deleterious effects of recA overexpression; however, the molecular
      mechanism has remained enigmatic. Here, we show that Mycobacterium tuberculosis
      RecX binds directly to M. tuberculosis RecA as well as M. smegmatis and E. coli
      RecA proteins in vivo and in vitro, but not single-stranded DNA binding protein.
      The direct association of RecX with RecA failed to regulate the specificity or
      extent of binding of RecA either to DNA or ATP, ligands that are central to
      activation of its functions. Significantly, RecX severely impeded ATP hydrolysis
      and the generation of heteroduplex DNA promoted by homologous, as well as
      heterologous, RecA proteins. These findings reveal a mode of negative regulation
      of RecA, and imply that RecX might act as an anti-recombinase to quell
      inappropriate recombinational repair during normal DNA metabolism.

PMID- 12218175
TI  - Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but
      distinct recognition of immunophilin-drug complexes.
AB  - Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, is the common
      target for two immunophilin-immunosuppressant complexes, cyclophilin A
      cyclosporin A (CyPA-CsA) and FKBP-FK506. How the two structurally distinct
      immunophilin-drug complexes bind the same target has remained unknown. We report
      the crystal structure of calcineurin (CN) in complex with CyPA-CsA at 2.8-A
      resolution. The CyPA-CsA complex binds to a composite surface formed by the
      catalytic and regulatory subunits of CN, where the complex of FK506 and its
      binding protein FKBP also binds. While the majority of the CN residues involved
      in the binding are common for both immunophilin-immunosuppressant complexes, a
      significant number of the residues are distinct. Unlike FKBP-FK506, CyPA-CsA
      interacts with Arg-122 at the active site of CN, implying direct involvement of
      CyPA-CsA in the regulation of CN catalysis. The simultaneous interaction of CyPA
      with both the composite surface and the active site of CN suggests that the
      composite surface may serve as a substrate recognition site responsible for the
      narrow substrate specificity of CN. The comparison of CyPA-CsA-CN with FKBP-FK506
      CN significantly contributes to understanding the molecular basis of regulation
      of CN activity by the immunophilin-immunosuppressant.

PMID- 12218176
TI  - Integrated classification of lung tumors and cell lines by expression profiling.
AB  - The utility of cancer cell lines depends largely on their accurate
      classification, commonly based on histopathological diagnosis of the cancers from
      which they were derived. However, because cancer is often heterogeneous, the cell
      line, which also has the opportunity to alter in vitro, may not be
      representative. Yet without the overall architecture used in histopathological
      diagnosis of fresh samples, reclassification of cell lines has been difficult.
      Gene-expression profiling accurately reproduces histopathological classification
      and is readily applicable to cell lines. Here, we compare the gene-expression
      profiles of 41 cell lines with 44 tumors from lung cancer. These profiles were
      generated after hybridization of samples to four replicate 7,685-element cDNA
      microarrays. After removal of genes that were uniformly up- or down-regulated in
      fresh compared with cell-line samples, cluster analysis produced four major
      branch groups. Within these major branches, fresh tumor samples essentially
      clustered according to pathological type, and further subclusters were seen for
      both adenocarcinoma (AC) and small cell lung carcinoma (SCLC). Four of eight
      squamous cell carcinoma (SCC) cell lines clustered with fresh SCC, and 11 of 13
      SCLC cell lines grouped with fresh SCLC. In contrast, although none of the 11 AC
      cell lines clustered with AC tumors, three clustered with SCC tumors and six with
      SCLC tumors. Although it is possible that preexisting SCC or SCLC cells are being
      selected from AC tumors after establishment of cell lines, we propose that, even
      in situ, AC will ultimately progress toward one of two poorly differentiated
      phenotypes with expression profiles resembling SCC or SCLC.

PMID- 12218177
TI  - Bcrp1 gene expression is required for normal numbers of side population stem
      cells in mice, and confers relative protection to mitoxantrone in hematopoietic
      cells in vivo.
AB  - Hematopoietic stem cells (HSCs) can be identified by a "side population" (SP)
      phenotype. Previous studies have implicated the ATP binding cassette transporter
      genes Mdr1a/1b and/or Bcrp1 in the SP phenotype. To define the relative role of
      these transporters, we generated Bcrp1 null mice and evaluated HSCs both
      functionally and phenotypically. Loss of Bcrp1 gene expression, but not Mdr1a/1b,
      led to a significant reduction in the number of SP cells in the bone marrow and
      in skeletal muscle. In the bone marrow, there was a nearly absolute loss of
      lineage negative, c-Kit-positive, Sca-1-positive SP cells, and the residual SP
      cells were depleted of repopulating cells in a transplant assay, demonstrating
      that Bcrp1 expression is necessary for the SP phenotype in HSCs. Furthermore,
      Bcrp1 null hematopoietic cells were significantly more sensitive to mitoxantrone
      in drug-treated transplanted mice. These results show that Bcrp1 gene expression
      alone defines the SP stem cell phenotype, and suggest that the physiological
      function of Bcrp1 expression in HSCs is to provide protection from cytotoxic
      substrates.

PMID- 12218178
TI  - Engineering growing tissues.
AB  - Regenerating or engineering new tissues and organs may one day allow routine
      replacement of lost or failing tissues and organs. However, these engineered
      tissues must not only grow to fill a defect and integrate with the host tissue,
      but often they must also grow in concert with the changing needs of the body over
      time. We hypothesized that tissues capable of growing with time could be
      engineered by supplying growth stimulus signals to cells from the biomaterial
      used for cell transplantation. In this study, chondrocytes and osteoblasts were
      cotransplanted on hydrogels modified with an RGD-containing peptide sequence to
      promote cell multiplication. New bone tissue was formed that grew in mass and
      cellularity by endochondral ossification in a manner similar to normal long-bone
      growth. Transplanted cells organized into structures that morphologically and
      functionally resembled growth plates. These engineered tissues could find utility
      in treating diseases and injuries of the growth plate, testing the effect of
      experimental drugs on growth-plate function and development, and investigating
      the biology of long-bone growth. Furthermore, this concept of promoting the
      growth of engineered tissues could find great utility in engineering numerous
      tissue types by way of the transplantation of a small number of precursor cells.

PMID- 12218179
TI  - Induction of cyclooxygenase-2 in a mouse model of Peutz-Jeghers polyposis.
AB  - Inactivating germ-line mutations of LKB1 lead to Peutz-Jeghers syndrome (PJS). We
      have generated mice heterozygous for a targeted inactivating allele of Lkb1 and
      found that they develop severe gastrointestinal polyposis. In all cases, the
      polyps arising in the Lkb1+/- mice were found to be hamartomas that were
      histologically indistinguishable from polyps resected from PJS patients,
      indicating that Lkb1+/- mice model human PJS polyposis. No evidence for
      inactivation of the remaining wild-type Lkb1 allele in Lkb1+/- -associated polyps
      was observed. Moreover, polyps and other tissues in heterozygote animals
      exhibited reduced Lkb1 levels and activity, indicating that Lkb1 was
      haploinsufficient for tumor suppression. Analysis of the molecular mechanisms
      characterizing Lkb1+/- polyposis revealed that cyclooxygenase-2 (COX-2) was
      highly up-regulated in murine polyps concomitantly with activation of the
      extracellular signal-regulated kinases 1 and 2 (Erk1/2). Subsequent examination
      of a large series of human PJS polyps revealed that COX-2 was also highly up
      regulated in the majority of these polyps. These findings thereby identify COX-2
      as a potential target for chemoprevention in PJS patients.

PMID- 12218181
TI  - A simple method for probing the mechanical unfolding pathway of proteins in
      detail.
AB  - Atomic force microscopy is an exciting new single-molecule technique to add to
      the toolbox of protein (un)folding methods. However, detailed analysis of the
      unfolding of proteins on application of force has, to date, relied on protein
      molecular dynamics simulations or a qualitative interpretation of mutant data.
      Here we describe how protein engineering Phi value analysis can be adapted to
      characterize the transition states for mechanical unfolding of proteins. Single
      molecule studies also have an advantage over bulk experiments, in that partial
      Phi values arising from partial structure in the transition state can be clearly
      distinguished from those averaged over alternate pathways. We show that unfolding
      rate constants derived in the standard way by using Monte Carlo simulations are
      not reliable because of the errors involved. However, it is possible to
      circumvent these problems, providing the unfolding mechanism is not changed by
      mutation, either by a modification of the Monte Carlo procedure or by comparing
      mutant and wild-type data directly. The applicability of the method is tested on
      simulated data sets and experimental data for mutants of titin I27.

PMID- 12218180
TI  - Act locally and think globally: intracerebral testosterone implants induce
      seasonal-like growth of adult avian song control circuits.
AB  - There is pronounced seasonal plasticity in the morphology of the neural circuits
      that regulate song behavior in adult songbirds, primarily in response to changes
      in plasma testosterone (T) levels. Most song nuclei have androgen receptors.
      Afferent input from the telencephalic nucleus HVc (also known as the "high vocal
      center") is necessary for seasonal growth of the direct efferent target nuclei RA
      and area X. We asked here whether T-stimulated growth of HVc is sufficient to
      induce growth of its efferent nuclei. Intracerebral T implants were placed
      unilaterally near HVc or RA in photosensitive adult male white-crowned sparrows
      for one month. The T implant near HVc produced significant growth of the
      ipsilateral (but not contralateral) HVc, RA, and area X, and increased neuronal
      number in the ipsilateral HVc. The T implant near RA did not produce selective
      growth of ipsilateral RA, HVc, or area X. Intracerebral T implants did not
      elevate plasma T levels, nor did they stimulate growth of two peripheral androgen
      sensitive targets, the syrinx and the cloacal protuberance. These results suggest
      that seasonal growth of the adult song circuits results from T acting directly on
      HVc, which then stimulates the growth of RA and area X transynaptically.

PMID- 12218182
TI  - Mouse transferrin receptor 1 is the cell entry receptor for mouse mammary tumor
      virus.
AB  - Enveloped viruses enter cells by binding to their entry receptors and fusing with
      the membrane at the cell surface or after trafficking through acidic endosomal
      compartments. Species-specific virus tropism is usually determined by these entry
      receptors. Because mouse mammary tumor virus (MMTV) is unable to infect Chinese
      hamster cells, we used phenotypic screening of the T31 mouse/hamster radiation
      hybrid panel to map the MMTV cell entry receptor gene and subsequently found that
      it is transferrin receptor 1. MMTV-resistant human cells that expressed mouse
      transferrin receptor 1 became susceptible to MMTV infection, and treatment of
      mouse cells with a monoclonal antibody that down-regulated cell surface
      expression of the receptor blocked infection. MMTV, like vesicular stomatitis
      virus, depended on acid pH for infection. MMTV may use transferrin receptor 1, a
      membrane protein that is endocytosed via clathrin-coated pits and traffics
      through the acidic endosomes, to rapidly get to a compartment where acid pH
      triggers the conformational changes in envelope protein required for membrane
      fusion.

PMID- 12218183
TI  - The two-component system BvrR/BvrS essential for Brucella abortus virulence
      regulates the expression of outer membrane proteins with counterparts in members
      of the Rhizobiaceae.
AB  - The Brucella BvrR/BvrS two-component regulatory system is homologous to the
      ChvI/ChvG systems of Sinorhizobium meliloti and Agrobacterium tumefaciens
      necessary for endosymbiosis and pathogenicity in plants. BvrR/BvrS controls cell
      invasion and intracellular survival. Probing the surface of bvrR and bvrS
      transposon mutants with monoclonal antibodies showed all described major outer
      membrane proteins (Omps) but Omp25, a protein known to be involved in Brucella
      virulence. Absence of Omp25 expression was confirmed by two-dimensional
      electrophoresis of envelope fractions and by gene reporter studies. The
      electrophoretic analysis also revealed reduction or absence in the mutants of a
      second set of protein spots that by matrix-assisted laser desorption ionization
      MS and peptide mass mapping were identified as a non-previously described Omp
      (Omp3b). Because bvrR and bvrS mutants are also altered in cell-surface
      hydrophobicity, permeability, and sensitivity to surface-targeted bactericidal
      peptides, it is proposed that BvrR/BvrS controls cell envelope changes necessary
      to transit between extracellular and intracellular environments. A genomic search
      revealed that Omp25 (Omp3a) and Omp3b belong to a family of Omps of plant and
      animal cell-associated alpha-Proteobacteria, which includes Rhizobium
      leguminosarum RopB and A. tumefaciens AopB. Previous work has shown that RopB is
      not expressed in bacteroids, that AopB is involved in tumorigenesis, and that
      dysfunction of A. tumefaciens ChvI/ChvG alters surface properties. It is thus
      proposed that the BvrR/BvrS and Omp3 homologues of the cell-associated alpha
      Proteobacteria play a role in bacterial surface control and host cell
      interactions.

PMID- 12218184
TI  - A global pH sensor: Agrobacterium sensor protein ChvG regulates acid-inducible
      genes on its two chromosomes and Ti plasmid.
AB  - A sensor protein ChvG is part of a chromosomally encoded two-component regulatory
      system ChvG/ChvI that is important for the virulence of Agrobacterium
      tumefaciens. However, it is not clear what genes ChvG regulates or what signal(s)
      it senses. In this communication, we demonstrate that ChvG is involved in the
      regulation of acid-inducible genes, including aopB and katA, residing on the
      circular and linear chromosomes, respectively, and the tumor-inducing (Ti)
      plasmid-harbored vir genes, virB and virE. ChvG was absolutely required for the
      expression of aopB and very important for the expression of virB and virE.
      However, it was responsible only for the responsiveness of katA and, to a limited
      extent, the vir genes to acidic pH. ChvG appears to play a role in katA
      expression by repressing katA at neutral pH. ChvG had no effect on the expression
      of two genes that were not acid-inducible. Because ChvG regulates unlinked acid
      inducible genes encoding different functions in different ways, we hypothesize
      that ChvG is a global sensor protein that can directly or indirectly sense
      extracellular acidity. We also analyzed the re-sequenced chvG and found that ChvG
      is more homologous to its Sinorhizobium meliloti counterpart ExoS than was
      previously thought. Full-length ChvG is conserved in members of the alpha
      proteobacteria, whereas only the C-terminal kinase domain is conserved in other
      bacteria. Sensing acidity appears to enable Agrobacterium to coordinate its
      coping with the environment of wounded plants to cause tumors.

PMID- 12218185
TI  - Molecular cloning and functional expression of the first insect FMRFamide
      receptor.
AB  - FMRFamide and FMRFamide-related neuropeptides are extremely widespread and
      abundant in invertebrates and have numerous important functions. Here, we have
      cloned a Drosophila orphan receptor, and stably expressed it in Chinese hamster
      ovary cells. Screening of a peptide library revealed that the receptor reacted
      with high affinity to FMRFamide (EC50, 6 x 10(-9) M). The intrinsic Drosophila
      FMRFamide peptides are known to be synthesized as a large preprohormone,
      containing at least 13 related FMRFamide peptides (8 distinct FMRFamides).
      Screening of these intrinsic Drosophila FMRFamides showed that the receptor had
      highest affinity to Drosophila FMRFamide-6 (PDNFMRFamide) (EC50, 9 x 10(-10) M),
      whereas it had a somewhat lower affinity to Drosophila FMRFamide-2
      (DPKQDFMRFamide) (EC50, 3 x 10(-9) M) and considerably less affinity to the other
      Drosophila FMRFamide-related peptides. To our knowledge, this article is the
      first report on the molecular identification of an invertebrate FMRFamide
      receptor.

PMID- 12218186
TI  - A role for glutathione peroxidase in protecting pancreatic beta cells against
      oxidative stress in a model of glucose toxicity.
AB  - Antioxidant drugs have been reported to protect pancreatic islets from the
      adverse effects of chronic exposure to supraphysiological glucose concentrations.
      However, glucose has not been shown to increase intracellular oxidant load in
      islets, nor have the effects of increasing or inhibiting glutathione peroxidase
      (GPx) activity on islet resistance to sugar-induced oxidant stress been studied.
      We observed that high glucose concentrations increased intracellular peroxide
      levels in human islets and the pancreatic beta cell line, HIT-T15. Inhibition of
      gamma-glutamylcysteine synthetase (gammaGCS) by buthionine sulfoximine augmented
      the increase in islet peroxide and decrease in insulin mRNA levels, content, and
      secretion in islets and HIT-T15 cells induced by ribose. Adenoviral
      overexpression of GPx increased GPx activity and protected islets against adverse
      effects of ribose. These results demonstrate that glucose and ribose increase
      islet peroxide accumulation and that the adverse consequences of ribose-induced
      oxidative stress on insulin mRNA, content, and secretion can be augmented by a
      glutathione synthesis inhibitor and prevented by increasing islet GPx activity.
      These observations support the hypothesis that oxidative stress is one mechanism
      for glucose toxicity in pancreatic islets.

PMID- 12218187
TI  - The hDcp2 protein is a mammalian mRNA decapping enzyme.
AB  - Decapping of mRNA is a critical step in eukaryotic mRNA turnover, yet the
      proteins involved in this activity remain elusive in mammals. We identified the
      human Dcp2 protein (hDcp2) as an enzyme containing intrinsic decapping activity.
      hDcp2 specifically hydrolyzed methylated capped RNA to release m(7)GDP; however,
      it did not function on the cap structure alone. hDcp2 is therefore functionally
      distinct from the recently identified mammalian scavenger decapping enzyme, DcpS.
      hDcp2-mediated decapping required a functional Nudix (nucleotide diphosphate
      linked to an X moiety) pyrophosphatase motif as mutations in conserved amino
      acids within this motif disrupted the decapping activity. hDcp2 is detected
      exclusively in the cytoplasm and predominantly cosediments with polysomes.
      Consistent with the localization of hDcp2, endogenous Dcp2-like decapping
      activity was detected in polysomal fractions prepared from mammalian cells.
      Similar to decapping in yeast, the presence of the poly(A) tail was inhibitory to
      the endogenous decapping activity, yet unlike yeast, competition of cap-binding
      proteins by cap analog did not influence the efficiency of decapping. Therefore
      the mammalian homologue of the yeast Dcp2 protein is an mRNA decapping enzyme
      demonstrated to contain intrinsic decapping activity.

PMID- 12218188
TI  - Involvement of PD-L1 on tumor cells in the escape from host immune system and
      tumor immunotherapy by PD-L1 blockade.
AB  - PD-1 is a receptor of the Ig superfamily that negatively regulates T cell antigen
      receptor signaling by interacting with the specific ligands (PD-L) and is
      suggested to play a role in the maintenance of self-tolerance. In the present
      study, we examined possible roles of the PD-1/PD-L system in tumor immunity.
      Transgenic expression of PD-L1, one of the PD-L, in P815 tumor cells rendered
      them less susceptible to the specific T cell antigen receptor-mediated lysis by
      cytotoxic T cells in vitro, and markedly enhanced their tumorigenesis and
      invasiveness in vivo in the syngeneic hosts as compared with the parental tumor
      cells that lacked endogenous PD-L. Both effects could be reversed by anti-PD-L1
      Ab. Survey of murine tumor lines revealed that all of the myeloma cell lines
      examined naturally expressed PD-L1. Growth of the myeloma cells in normal
      syngeneic mice was inhibited significantly albeit transiently by the
      administration of anti-PD-L1 Ab in vivo and was suppressed completely in the
      syngeneic PD-1-deficient mice. These results suggest that the expression of PD-L1
      can serve as a potent mechanism for potentially immunogenic tumors to escape from
      host immune responses and that blockade of interaction between PD-1 and PD-L may
      provide a promising strategy for specific tumor immunotherapy.

PMID- 12218189
TI  - Cbl-directed monoubiquitination of CIN85 is involved in regulation of ligand
      induced degradation of EGF receptors.
AB  - Addition of ubiquitin or ubiquitin chains to target proteins leads to their mono-
      or polyubiquitination, respectively. Whereas polyubiquitination targets proteins
      for degradation, monoubiquitination is thought to regulate receptor
      internalization and endosomal sorting. Cbl proteins are major ubiquitin ligases
      that promote ligand-dependent polyubiquitination and degradation of receptor
      tyrosine kinases. They also recruit CIN85-endophilin in the complex with
      activated receptors, thus controlling receptor endocytosis. Here we show that the
      adaptor protein CIN85 and its homologue CMS are monoubiquitinated by Cbl/Cbl-b
      after epidermal growth factor (EGF) stimulation. Monoubiquitination of CIN85
      required direct interactions between CIN85 and Cbl, the intact RING finger domain
      of Cbl and a ubiquitin acceptor site present in the carboxyl terminus of CIN85.
      Cbl-b and monoubiquitinated CIN85 are found in the complex with polyubiquitinated
      EGF receptors during prolonged EGF stimulation and are degraded together in the
      lysosome. Dominant interfering forms of CIN85, which have been shown previously
      to delay EGF receptor degradation, were also impaired in their
      monoubiquitination. Thus, our data demonstrate that Cbl/Cbl-b can mediate
      polyubiquitination of cargo as well as monoubiquitination of CIN85 to control
      endosomal sorting and degradation of receptor tyrosine kinases.

PMID- 12218190
TI  - Cytoplasmic poly(A) polymerases mediate cellular responses to S phase arrest.
AB  - The S-M checkpoint delays mitosis until DNA replication is complete; cells
      defective in this checkpoint lose viability when DNA replication is inhibited.
      This inviability can be suppressed in fission yeast by overexpression of Cid1 or
      the related protein Cid13. Fission yeast contain six cid1/cid13-like genes,
      whereas budding yeast has just two, TRF4 and TRF5. Trf4 and Trf5 were recently
      reported to comprise an essential DNA polymerase activity required for the
      establishment of sister chromatid cohesion. In contrast, we find that Cid1 is not
      a DNA polymerase but instead uses RNA substrates and has poly(A) polymerase
      activity. Unlike the previously characterized yeast poly(A) polymerase, which is
      a nuclear enzyme, Cid1 and Cid13 are constitutively cytoplasmic. Cid1 has a
      degree of substrate specificity in vitro, consistent with the notion that it
      targets a subset of cytoplasmic mRNAs for polyadenylation in vivo, hence
      increasing their stability and/or efficiency of translation. Preferred Cid1
      targets presumably include mRNAs encoding components of the S-M checkpoint,
      whereas Cid13 targets are likely to be involved in dNTP metabolism. Cytoplasmic
      polyadenylation is known to be an important regulatory mechanism during early
      development in animals. Our findings in yeast suggest that this level of gene
      regulation is of more general significance in eukaryotic cells.

PMID- 12218192
TI  - Acceptance rates and publication times.

PMID- 12218193
TI  - The BOS intercollegiate M Orth prize of the Royal Colleges of England and Glasgow
      2000.

PMID- 12218191
TI  - Physical constraints and functional characteristics of transcription factor-DNA
      interaction.
AB  - We study theoretical "design principles" for transcription factor (TF)-DNA
      interaction in bacteria, focusing particularly on the statistical interaction of
      the TFs with the genomic background (i.e., the genome without the target sites).
      We introduce and motivate the concept of programmability, i.e., the ability to
      set the threshold concentration for TF binding over a wide range merely by
      mutating the binding sequence of a target site. This functional demand, together
      with physical constraints arising from the thermodynamics and kinetics of TF-DNA
      interaction, leads us to a narrow range of "optimal" interaction parameters. We
      find that this parameter set agrees well with experimental data for the
      interaction parameters of a few exemplary prokaryotic TFs, which indicates that
      TF-DNA interaction is indeed programmable. We suggest further experiments to test
      whether this is a general feature for a large class of TFs.

PMID- 12218194
TI  - Combined orthodontic-dentofacial orthopedic treatment of a Class II Division 2
      patient with severe deep bite.

PMID- 12218195
TI  - Manipulation of digital photographs.
AB  - This article provides simple details of what to do with digital images once they
      have been captured. Inspection of the images as 'thumbnails' using Exif viewer is
      described, as well as zooming in to check detail contained on the images. Storage
      of every orthodontic patient using the popular programme, Dentofacial Showcase is
      described in some detail. For more formal verbal presentations or written
      material intended for display Microsoft Powerpoint is the programme of choice.
      Transfer of the images between the three programmes is described in detail, as
      well as recommended layouts for written and verbal presentations.

PMID- 12218197
TI  - A qualitative study of teenagers' decisions to undergo orthodontic treatment with
      fixed appliance.
AB  - OBJECTIVE: The aim of this study was to describe thoughts and values influencing
      young people's choices to undergo orthodontic treatment. SUBJECTS AND METHODS:
      Twenty-eight patients (11 boys), aged 13-19 years, at an orthodontic clinic in
      the western part of Sweden participated. Open, taped interviews, lasting about 1
      hour, were conducted with each subject and analysed by the grounded theory
      method. Five descriptive categories, each related to several subcategories, were
      generated in the analysis and labelled: 'being like everyone else', 'being
      diagnosed', 'focusing on the mouth', 'obeying social norms' and 'forced decision
      making'. OUTCOME: Category forced decision-making was identified as a core
      category, describing the power in the social process, resulting in the decision
      to undergo orthodontic treatment. CONCLUSIONS: Motivation for the decision to
      undergo orthodontic treatment seemed to be social norms, and the beauty culture
      in their reference group and in society in general. The teenagers were not fully
      conscious of these external influences. Their opinion, as a group, was that they
      had made an independent decision to undergo orthodontic treatment.

PMID- 12218198
TI  - Orthodontic adhesives: a systematic review.
AB  - OBJECTIVES: To evaluate which orthodontic adhesives (a). bond orthodontic
      brackets to teeth more reliably and (b). are more effective at preventing
      decalcification. DATA SOURCES: The search strategy for the literature review was
      carried out according to the standard Cochrane systematic review methodology. The
      Cochrane Clinical Trials Register and the Cochrane Oral Health Group Specialized
      Register were searched for randomized clinical trials and controlled clinical
      trials. All volumes that had not already been assessed by the Oral Health Group
      in the European Journal of Orthodontics, American Journal of Orthodontics,
      Journals of Orthodontics, and Angle Orthodontist were hand-searched. Inclusion
      and exclusion criteria were applied when considering the studies to be included
      in this review. DATA SELECTION: The primary outcome measure was the failure of
      the orthodontic adhesive. A secondary outcome of decalcification occurring around
      the orthodontic bracket was also recorded, if data were available. DATA
      EXTRACTION: Two randomized clinical trials and one controlled clinical trial were
      identified that fulfilled all the inclusion and exclusion criteria. The trials
      compared: (a). light- and chemically-cured composite; (b). chemically-cured
      composite and conventional glass ionomer cement; and (c). chemically-cured
      composite and light-cured compomer. DATA SYNTHESIS: Each paper was quality
      assessed by two people independently. A qualitative analysis of the trials in the
      review is presented. The data presentation, for the majority of the trials,
      precluded the use of suggested Cochrane Health Group statistical analysis.
      CONCLUSIONS: It is difficult to draw any conclusions from this review; however,
      suggestions are made for methods of improving future research involving
      orthodontic adhesives.

PMID- 12218199
TI  - Development and use of a taxonomy to carry out a systematic review of the
      literature on methods described to effect distal movement of maxillary molars.
AB  - OBJECTIVE: To devise a taxonomy for the assessment of the orthodontic literature
      on methods described to effect distal movement of maxillary molars, to test the
      taxonomy for inter-assessor reliability, and to use it to classify studies in a
      systematic review of the literature. DATA SOURCES: Articles appearing in the
      American Journal of Orthodontics and Dentofacial Orthopedics, Angle Orthodontist,
      (British) Journal of Orthodontics, European Journal of Orthodontics, and the
      Journal of Clinical Orthodontics between 1988 and 1998. Data selection Articles
      describing or evaluating the effect of appliances known or thought to have a
      distalizing effect on maxillary molars. DATA EXTRACTION: A taxonomy was designed,
      tested by two reviewers independently to assess levels of agreement, and then
      used to record the features of the articles in a systematic review of the
      literature. DATA SYNTHESIS: Kappa scores were used to assess the level of
      agreement between reviewers and found to be satisfactory. Studies were grouped
      according to study design and features of their methodology quantified.
      CONCLUSIONS: Having devised and tested the taxonomy, we found that the quality of
      evidence for any method of moving maxillary molars distally was not high.

PMID- 12218200
TI  - The effect of pumicing on the in vivo use of a resin modified glass
      poly(alkenoate) cement and a conventional no-mix composite for bonding
      orthodontic brackets.
AB  - OBJECTIVE: Pumicing of the enamel prior to direct bonding with conventional
      diacrylate bonding agents has been shown to be unnecessary. It is not known
      whether this is also the case with resin-modified glass poly(alkenoate) cements.
      The aims of this study were two-fold: (a). to determine whether pumicing prior to
      bonding has an effect on the in vivo failure of brackets bonded with either Right
      On or Fuji II LC; (b). to determine whether there is a difference in the in vivo
      failure of brackets bonded with either Right-On or Fuji II LC. Design A cross
      mouth controlled clinical trial was performed on a total of 60 patients in which
      the variables under test were pumicing or not pumicing of the enamel prior to
      bonding using two different bonding agents. MAIN OUTCOME MEASURES: The
      measurement variable was bond failure over an 18-month period. RESULTS AND
      CONCLUSIONS: Prior pumicing of the enamel has no effect on in vivo failure when
      using either a conventional diacrylate or a resin modified glass poly(alkenoate)
      cement. A greater number of bonds failed with the resin-modified glass
      poly(alkenoate) cement.

PMID- 12218201
TI  - Moving forward by looking back: 'retrospective' clinical studies.

PMID- 12218205
TI  - The role of implants in orthodontics.

PMID- 12218206
TI  - Utilization of acidophil bodies in the diagnosis of recurrent hepatitis C
      infection after orthotopic liver transplantation.
AB  - BACKGROUND: The distinction between acute rejection and early recurrent hepatitis
      C infection (RHCV) in the setting of orthotopic liver transplantation is often
      difficult. In liver biopsies acidophil bodies and lobular hepatitis are used to
      suggest a diagnosis of RHCV over rejection, however, the reliability of this
      practice has not been established. Because portal tract changes in RHCV and
      rejection often overlap, we sought to determine whether the degree of hepatocyte
      acidophil body formation seen on liver biopsies could be used to distinguish
      between these two conditions. METHODS: Quantification of acidophil bodies was
      performed on liver biopsies in orthotopic liver transplant patients with RHCV (n
      = 10), non-hepatitis C orthotopic liver transplant patients with uncomplicated
      rejection episodes (n = 10) and non-transplant patients with chronic hepatitis C
      infection (n = 10). Hematoxylin and Eosin stained slides from all three groups
      were randomized and tissue segments 1.0 cm in length and of variable width (0.04
      0.13 cm) were examined at 200x magnification in a blinded fashion by two
      pathologists in order to quantify the number of acidophil bodies/cm(2). Lobular
      chronic inflammation was also graded on a 0-3+ scale. RESULTS: Liver biopsies
      taken at the onset of RHCV exhibited 606 +/- 101 acidophil bodies/cm(2) (mean +/-
      standard error of mean, range 200-1390). These counts were significantly greater
      (P =.0061, paired 2-tailed t-test) than the 241 +/- 53 acidophil bodies/cm(2)
      (range 80-514) for acute rejection, and the 194 +/- 21 acidophil bodies/cm(2)
      (range 100-333) for non-liver transplant chronic hepatitis C infection (P
      =.0013). No difference in lobular inflammation between index RHCV and rejection
      biopsies was detected. CONCLUSIONS: Although there is overlap, on average there
      are twice as many acidophil bodies in the initial stage of RHCV when compared
      with acute rejection (average of 55 per linear cm in RHCV versus 21 per linear cm
      for rejection). Lobular inflammation was not a reliable indicator of the initial
      onset of RHCV.

PMID- 12218207
TI  - Characteristics of tumors in lymph vessels play an important role in the tumor
      progression of invasive ductal carcinoma of the breast: a prospective study.
AB  - It is unknown whether the characteristics of tumor cells in lymph vessels play an
      important role in the tumor progression of invasive ductal carcinoma (IDC) of the
      breast. The purpose of this study was to investigate the significance of the
      characteristics of tumor cells in the lymph vessels in relation to the tumor
      progression in 393 IDC patients in comparison with well-known histological
      parameters. The dimensions of lymph vessel tumor emboli were measured, and their
      structural features, nuclear atypia, and numbers of mitotic and apoptotic figures
      were also assessed. Multiple regression analysis showed the dimension, the
      distance, the number of mitotic figures, the number of apoptotic figures, and
      papillary features of lymph vessel tumor emboli to be significantly associated
      with the increased number of cells invading the lymph vessels (P < .05). The Cox
      proportional hazard multivariate analyses showed that more than six apoptotic
      figures in lymph vessel tumor emboli significantly increased the hazard rates
      (HRs) of tumor recurrence and death in IDCs without nodal metastasis and that
      more than four mitotic figures in lymph vessel tumor emboli significantly
      increased the HRs of tumor recurrence and death in IDCs with nodal metastasis (P
      < .05). The present study showed that the histological characteristics of tumor
      cells in lymph vessels play a very important role in the tumor progression of
      IDCs.

PMID- 12218208
TI  - Histologic and in situ viral findings in the myocardium in cases of sudden,
      unexpected death.
AB  - The purpose of this study was to do in situ viral detection in myocardial tissues
      of individuals who suffered sudden unexpected death and to correlate the results
      with the postmortem histopathologic findings. Thirteen cases were identified and
      the heart tissues were analyzed for adenovirus, cytomegalovirus, Epstein Barr
      virus, herpes simplex virus 1 and 2, human immunodeficiency virus 1 (HIV-1),
      influenza A, influenza B, parvovirus, rotavirus, picornavirus (including separate
      primers for enterovirus and Coxsackie virus A and B), varicella zoster virus, and
      respiratory syncytial virus. Thirteen individuals aged 2 to 67 years were
      studied. In each case, polymerase chain reaction-amplified viral RNA was detected
      in situ: Coxsackie virus B (5 cases), rotavirus (4 cases), HIV-1 (2 cases),
      influenza A (1 case), and influenza B (1 case). Immunohistochemical detection of
      viral proteins was found in the five Coxsackie virus cases and four rotavirus
      cases. The mononuclear inflammatory infiltrate was diffuse and marked only in the
      cases of influenza A and HIV-1, as well as one of the Coxsackie virus and
      rotavirus cases, respectively. Immunohistochemical analysis showed that the most
      common cell type in the inflammatory infiltrates was CD68-positive macrophages.
      Direct myocyte infection was most prominent in the cases of Coxsackie virus
      infection. In summary, in situ viral detection was documented in each case of
      idiopathic myocarditis associated with sudden, unexpected death; in 6/13 cases,
      the myocarditis was focal and minimal. Although Coxsackie virus was, as expected,
      the most common virus noted, other viruses including rotavirus and HIV-1 were
      also observed, highlighting the need for comprehensive viral and histologic
      analyses in such cases.

PMID- 12218209
TI  - Expression of CD10 in malignant mullerian mixed tumors and adenosarcomas: an
      immunohistochemical study.
AB  - CD10 has been demonstrated to be positive in endometrial stromal sarcoma (ESS)
      and thus is useful in establishing the diagnosis, but its expression in malignant
      mullerian mixed tumor (MMMT) and mullerian adenosarcoma remains to be clarified.
      In this study, 12 cases of MMMT (9 uterine, 2 tubal, and 1 metastatic), 6 cases
      of mullerian adenosarcoma (three corporeal, two cervical, and one tubal), and 7
      cases of primary uterine sarcomas had their tissues examined
      immunohistochemically for expression of CD10, desmin, myoglobin, alpha-smooth
      muscle actin (SMA), and cytokeratin. Of the primary uterine sarcomas, two were
      primary rhabdomyosarcomas (one cervical and one corporeal), two were ESSs, two
      were high-grade leiomyosarcomas, and one was a high-grade endometrial sarcoma.
      Sarcomatous components in all cases of MMMT and mullerian adenosarcoma, as well
      as all uterine sarcomas, were positive for CD10, showing moderate to marked
      staining intensity with varying distribution except in one MMMT, which showed
      weak and very focal staining. In four MMMTs, three adenosarcomas, and one
      rhabdomyosarcoma, myoglobin- and/or desmin-positive rhabdomyoblastic cells were
      positive for CD10. The immunoreactivity for CD10 showed the same distribution for
      alpha-SMA and myoglobin in three and two MMMTs, respectively. In five cases of
      MMMT, carcinomatous components were focally positive for CD10, and in two cases
      small populations of round or short spindle cells in sarcomatous components were
      positive for CD10, alpha-SMA, and cytokeratin (CAM5.2). These results indicate
      that CD10 expression is not restricted to ESS but can be positive in MMMT and
      mullerian adenosarcoma as well as in a variety of uterine tumors including high
      grade leiomyosarcoma and rhabdomyosarcoma. CD10 expression might be one of the
      characteristics of mullerian system-derived neoplastic mesenchymal cells.

PMID- 12218210
TI  - Expression of ALK1 and p80 in inflammatory myofibroblastic tumor and its
      mesenchymal mimics: a study of 135 cases.
AB  - Abnormalities of chromosome 2p23 with expression of ALK1 and p80 occur in both
      inflammatory myofibroblastic tumor (IMT) and anaplastic large cell lymphoma. This
      immunohistochemical study investigates whether the ALK family of neoplasms
      includes fibroblastic-myofibroblastic, myogenic, and spindle cell tumors.
      Formalin-fixed paraffin-embedded archival tissues from 10 IMTs and 125 other soft
      tissue tumors were stained for ALK1 and p80 with standard immunohistochemistry.
      ALK1 and/or p80 reactivity was observed in a cytoplasmic pattern in IMT (4/10;
      40%), malignant peripheral nerve sheath tumor (4/10; 40%), rhabdomyosarcoma
      (6/31; 19%), leiomyosarcoma (1/10; 10%), and malignant fibrous histiocytoma
      (1/11; 9%). No staining was observed in nodular fasciitis, desmoid, infantile
      myofibromatosis, infantile fibrosarcoma, synovial sarcoma, leiomyoma, or
      myofibrosarcoma. Alveolar rhabdomyosarcomas (4/16; 25%) displayed a distinctive
      dot-like cytoplasmic positivity. No cases displayed nuclear reactivity.
      Fluorescent in situ hybridization on 12 of the positive cases revealed a
      combination of abnormalities including ALK break-apart signals, nucleophosmin
      (NPM)/ALK fusions, or extra copies of 2p23. This study demonstrates that in
      addition to IMT, abnormalities of ALK1 and p80 expression with a variety of
      structural chromosomal changes are found in several sarcomas, especially
      rhabdomyosarcoma and malignant peripheral nerve sheath tumor. Although
      immunoreactivity in non-IMTs cannot distinguish between structural abnormalities
      involving 2p23 or additional copies of 2p23, it supports the concept of ALK
      involvement in a larger group of neoplasms, some of which have other documented
      clonal abnormalities. In IMT, immunohistochemistry for ALK1 and p80 is useful as
      an indicator of a 2p23 abnormality, but it must be interpreted in the context of
      histologic and other clinicopathologic data if used as an adjunct to differential
      diagnosis.

PMID- 12218211
TI  - Lymphadenopathy due to Penicillium marneffei infection: diagnosis by fine needle
      aspiration cytology.
AB  - Penicillium marneffei is an opportunistic fungal infection that usually causes
      disseminated disease, mainly in immunocompromised individuals, especially those
      with HIV infection. Untreated cases are usually fatal. Diagnosis is traditionally
      made by biopsy and/or culture; successful diagnosis by fine needle aspiration
      (FNA) has only been reported once. We present eight cases of HIV-infected
      patients with lymphadenopathy caused by P. marneffei infection, in which the
      diagnosis was made by FNA. In all cases, intracellular and extracellular yeast
      forms were visualized, and the characteristic cross-septation of P. marneffei was
      highlighted by GMS staining. All diagnoses were confirmed by culture. Anti-fungal
      treatment for P. marneffei was initiated, resulting in marked clinical
      improvement. We conclude that a diagnosis of lymphadenopathy caused by P.
      marneffei can reliably be made by FNA. The diagnosis is more rapid than biopsy or
      culture, allowing rapid institution of therapy, particularly important in
      immunocompromised patients. In all our cases, not only were lymphoma and other
      causes of lymphadenopathy ruled out, but also the necessity for an open surgical
      biopsy was obviated. This can be especially beneficial to patients (e.g., three
      in our study) in which lymphadenopathy is confined to deep intra-abdominal nodes.

PMID- 12218212
TI  - Primary effusion lymphoma: cytopathologic diagnosis using in situ molecular
      genetic analysis for human herpesvirus 8.
AB  - Primary effusion lymphoma is a form of diffuse large B-cell lymphoma with
      neoplastic cells largely limited to proliferation within major body cavities.
      Human herpes virus-8 is both integral to and required for an unequivocal
      diagnosis of primary effusion lymphoma. Prior methods for virus identification
      include DNA extraction with Southern blot analysis or in situ hybridization from
      paraffin-embedded samples. Our aim is to examine the utility of human herpesvirus
      8 identification performed directly on smears from effusion samples by reverse
      transcriptase in situ polymerase chain reaction in patients with primary effusion
      lymphoma. Smears and cell block of body cavity fluids from five patients with
      effusions (three pleural, one peritoneal, and one both pleural and peritoneal)
      were examined microscopically by conventional Papanicolaou and Romanowsky (Diff
      Quik) staining, and by reverse transcriptase in situ polymerase chain reaction
      for human herpesvirus-8 detection. In situ hybridization was performed also for
      Epstein-Barr virus (EBER-1, -2), T-cell receptor-beta, and kappa (kappa) and
      lambda (lambda) mRNA in all cases. Five adults ranged from 40-81 years of age.
      Three adults were HIV positive, one was a renal transplant recipient, and the
      oldest patient (Case 3) had the unusual distinction of a normal immune status.
      Two of three HIV-seropositive patients had concurrent Kaposi sarcoma. All samples
      were cytologically similar with lymphocytes having large-cell, plasmablastic, and
      immunoblastic morphology. Malignant cells from effusions were as follows: human
      herpesvirus-8 positive (all five cases), exhibited kappa monoclonal light chain
      (five cases), Epstein-Barr virus positive (three cases), and T-cell beta-gene
      receptor positive (two cases). Diffuse large B-cell lymphoma was evident in one
      peritoneal nodule (< 10% human herpesvirus-8 positive cells in contrast to > 90%
      positive in effusions, all kappa positive). Six other tissue specimens (lung,
      bone marrow, spleen, lymph node) were human herpesvirus-8 negative, and showed no
      evidence of lymphoma. Reverse transcriptase in situ polymerase chain reaction
      demonstrated near-complete restriction of human herpesvirus-8-infected malignant
      lymphoid cells to those in body cavities. Definitive diagnosis of primary
      effusion lymphoma is possible directly from cytologic smears/cell block by
      combining cytologic morphology with reverse transcriptase in situ polymerase
      chain reaction detection of human herpesvirus-8.

PMID- 12218213
TI  - Characteristic pattern of genetic aberrations in ovarian granulosa cell tumors.
AB  - The cytogenetic abnormalities of granulosa cell tumors (GCT) of the ovary are
      only partially known. Up to now, mainly numerical chromosomal aberrations have
      been described. Therefore we performed a comprehensive study on paraffin-embedded
      material of 20 GCT (17 adult, 3 juvenile; patient age between 16 and 78 y)
      combining comparative genomic hybridization (CGH); fluorescence in situ
      hybridization (FISH) using DNA-specific probes for chromosome 12, 17, 22, and X;
      DNA cytometry; and immunohistochemistry (inhibin, p53, Ki67). By DNA cytometry,
      16 of 20 tumors (80%) were diploid. However, 6 of 16 diploid tumors (37%) showed
      aberrations by FISH. FISH revealed monosomy 22 in 8/18 cases (40%); trisomy 12 in
      5/20 (25%); monosomy X in 2/20 (10%); and loss of chromosome 17 in one case (5%).
      The main findings by CGH were gains of chromosomes 12 (6 cases, 33%) and 14 (6
      cases, 33%) and losses of chromosomes 22 (7 cases, 35%) and X (1 case, 5%),
      mostly comprising whole chromosomes or chromosome arms. Inhibin and p53 were
      expressed in 100% and 95% of the tumors, respectively. The Ki67 index ranged from
      0% to 61%. Neither immunohistochemistry, nor DNA cytometry and molecular genetic
      analysis, provided statistically significant prognostic information. In summary,
      our study reveals a distinctive pattern of cytogenetic alterations in GCT. Our
      observations confirm earlier reports that trisomy 12 and 14 are frequent
      aberrations; however, monosomy 22 seemingly is even more prevalent.

PMID- 12218214
TI  - MUC2 is a molecular marker for pseudomyxoma peritonei.
AB  - Pseudomyxoma peritonei, a syndrome first described by Rokitansky in 1842, is an
      enigmatic, often fatal intra-abdominal disease characterized by dissecting
      gelatinous ascites and multifocal peritoneal epithelial implants secreting
      copious globules of extracellular mucin. Although much past interest in the
      syndrome has focused on the question of whether the disease arises from primary
      appendiceal or ovarian mucinous tumors of varying malignant potential, the
      accumulation of extracellular mucin with its resulting obstruction of abdominal
      viscera and adhesion formation is one major cause of this disease's morbidity and
      mortality irrespective of the origin or transformed status of the epithelium
      secreting it. Because of this and because of the recent discovery and cloning of
      a series of specific mucin genes responsible for mucin secretion and
      extracellular deposition, we decided to analyze cases of pseudomyxoma peritonei
      with specific mucin cDNAs and corresponding antibodies to identify a
      characteristic marker for this disease which ultimately might be targeted
      therapeutically. Our study specifically investigated MUC2 and MUC5AC because
      these two mucins possessed the physicochemical property of being gel-forming, a
      property exhibited by pseudomyxoma peritonei grossly. Expression of MUC2 and
      MUC5AC in pseudomyxoma peritonei and in accompanying and non-accompanying
      appendiceal and ovarian mucinous neoplasms were analyzed by in situ
      hybridization, immunocytochemistry and digital image analysis. A striking
      overexpression of both MUC2 and MUC5AC was observed in nearly all cases of
      pseudomyxoma peritonei of unknown and appendiceal origin. In these cases,
      however, MUC2 gene expression was more prominent. The mucin:cell ratio averaged
      10 to 1 in these cases. The primary ovarian mucinous tumors, some of which
      exhibited pseudomyxoma ovarii and/or peritoneal implants but not classic
      pseudomyxoma peritonei, in contrast, expressed only MUC5AC and gave rise to
      implants where the mucin:cell ratio averaged only 1 to 1. MUC2 overexpression
      then supported an intestinal rather than ovarian origin for true pseudomyxoma
      peritonei, irrespective of whether an appendiceal primary was documented. In all
      cases studied, the fidelity of MUC2 and MUC5AC expression held irrespective of
      the degree of malignant transformation which was present. MUC2 is therefore a
      reliable molecular marker for pseudomyxoma peritonei.

PMID- 12218215
TI  - Oncocytic adrenocortical carcinoma: a morphologic, immunohistochemical and
      ultrastructural study of four cases.
AB  - We present the clinical, histologic, immunohistochemical, and ultrastructural
      findings of four cases of non-functioning oncocytic adrenocortical carcinomas.
      The patients' ages ranged from 39 to 71 years. There was no sex predilection.
      Large yellow-tan tumors (8.5 to 17.0 cm), well demarcated from the adjacent
      kidney, were seen with a thin rim of normal adrenal gland along one edge. One
      tumor invaded the inferior vena cava and extended up to the level of the right
      atrium, and another metastasized to bone. The other two tumors had similar
      morphologic features and therefore were considered carcinomas. Histologic
      sections of all four cases showed a diffuse proliferation of polygonal neoplastic
      cells with large nuclei containing prominent nucleoli and abundant granular and
      eosinophilic cytoplasm. Occasional mononuclear and binucleated giant cells were
      noted in one case. There were rare mitotic figures (less than one per 10 high
      power fields). All tumors were immunoreactive for cytokeratins (AE1/AE3 and
      CAM5.2). Inhibin was focally expressed by one tumor and its bone metastasis.
      Ultrastructurally, the cytoplasm of the neoplastic cells was packed with
      innumerable mitochondria. Cytologic atypia or mitotic rate cannot reliably
      predict the biologic behavior of oncocytic adrenocortical neoplasms. Large tumor
      size (4/4), extracapsular extension (3/4), blood vessel invasion (2/4), necrosis
      (4/4), and metastasis (1/4) are features of malignancy for oncocytic
      adrenocortical carcinomas. The treatment of these tumors is complete surgical
      excision.

PMID- 12218217
TI  - Demonstration of immune complex deposits using fluorescence microscopy of
      hematoxylin and eosin-stained sections of Hollande's fixed renal biopsies.
AB  - A new method that may be useful in the evaluation of renal biopsies is described
      using fluorescence microscopy on standard hematoxylin and eosin-stained sections
      of kidney tissue fixed in Hollande's fixative. We describe brightly fluorescing
      immune complex deposits within glomerular basement membranes and mesangial
      matrices that correlate well with the results of standard direct
      immunofluorescence on frozen tissue and electron microscopy. In a blind analysis
      of 261 consecutive renal biopsies, we determine that this method has diagnostic
      utility for identification of immune complex glomerulonephritis and significantly
      extends the usefulness of standard histologic preparations before the use of
      special stains or procedures.

PMID- 12218216
TI  - Effect of duration of fixation on quantitative reverse transcription polymerase
      chain reaction analyses.
AB  - Increasingly, there is the need to analyze gene expression in tumor tissues and
      correlate these findings with clinical outcome. Because there are few tissue
      banks containing enough frozen material suitable for large-scale genetic
      analyses, methods to isolate and quantify messenger RNA (mRNA) from formalin
      fixed, paraffin-embedded tissue sections are needed. Recovery of RNA from
      routinely processed biopsies and quantification by the polymerase chain reaction
      (PCR) has been reported; however, the effects of formalin fixation have not been
      well studied. We used a proteinase K-salt precipitation RNA isolation protocol
      followed by TaqMan quantitative PCR to compare the effect of formalin fixation
      for 24, 48, and 72 hours and for 1 week in normal (2), oral epithelial dysplasia
      (3), and oral squamous cell carcinoma (4) specimens yielding 9 fresh and 36
      formalin-fixed samples. We also compared mRNA and protein expression levels using
      immunohistochemistry for epidermal growth factor receptor (EGFR), matrix
      metalloproteinase (MMP)-1, p21, and vascular endothelial growth factor (VEGF) in
      15 randomly selected and routinely processed oral carcinomas. We were able to
      extract RNA suitable for quantitative reverse transcription (RT) from all fresh
      (9/9) and formalin-fixed (36/36) specimens fixed for differing lengths of time
      and from all (15/15) randomly selected oral squamous cell carcinoma. We found
      that prolonged formalin fixation (>48 h) had a detrimental effect on quantitative
      RT polymerase chain reaction results that was most marked for MMP-1 and VEGF but
      less evident for p21 and EGFR. Comparisons of quantitative RT polymerase chain
      reaction and immunohistochemistry showed that for all markers, except p21, there
      was good correlation between mRNA and protein levels. p21 mRNA was overexpressed
      in only one case, but protein levels were elevated in all but one tumor,
      consistent with the established translational regulation of p21. These results
      show that RNA can be reliably isolated from formalin-fixed, paraffin-embedded
      tissue sections and can produce reliable quantitative RT-PCR data. However,
      results for some markers are adversely affected by prolonged formalin fixation
      times.

PMID- 12218218
TI  - Radiation-associated synovial sarcoma: clinicopathologic and molecular analysis
      of two cases.
AB  - Development of a soft-tissue sarcoma is an infrequent but well-known long-term
      complication of radiotherapy. Malignant fibrous histiocytomas, extraskeletal
      osteosarcomas, fibrosarcomas, malignant peripheral nerve sheath tumors, and
      angiosarcomas are most frequently encountered. Radiation-associated synovial
      sarcomas are exceptional. We report the clinicopathologic, immunohistochemical,
      and molecular features of two radiation-associated synovial sarcomas. One tumor
      developed in a 42-year-old female 17 years after external irradiation was given
      for breast carcinoma; the other occurred in a 34-year-old female who was
      irradiated at the age of 7 years for a nonneoplastic condition of the left hand.
      Both lesions showed morphologic features of monophasic spindle cell synovial
      sarcoma, were immunoreactive for cytokeratins, epithelial membrane antigen, CD99,
      CD117 (c-kit), and bcl-2 and bore the t(X;18) (SYT-SSX1) translocation. We
      conclude that synovial sarcoma has to be added to the list of radiation
      associated soft-tissue sarcomas.

PMID- 12218219
TI  - Keratocystoma of the parotid gland: a report of two cases of an unusual
      pathologic entity.
AB  - Benign salivary gland tumors composed of purely squamous cells are quite unusual
      and are not included in the World Health Organization classification. We have
      seen two benign parotid gland tumors characterized by multicystic spaces with
      stratified squamous linings and focal solid epithelial nests. Seifert et al.
      recently described such a case as a choristoma; we, however, herein propose a new
      designation, keratocystoma, for this unique tumor group, because of its
      distinctive histological features. These tumors occurred in men aged 18 and 38
      years with enlarging parotid gland tumors. Both had largely similar gross and
      histological features, with some variations. The epithelium lining of the cysts
      showed apparent keratinization through a parakeratotic or orthokeratotic pathway
      without forming a granular cell layer. Stratification of the epithelium was
      always regularly oriented from the outer basal to the inner keratotic cell layer.
      Focally, the outer layer had bud-like protrusions. In some areas, solid squamous
      cell islands surrounded by basement membrane were enclosed within the collagenous
      stroma. These cystic and solid structures were randomly distributed, showing no
      definite lobular architecture. All of the tumor cells had uniform, bland nuclei
      and abundant eosinophilic cytoplasm. Scattered mitotic figures were observed,
      limited to the outer epithelial layer, and showed no abnormal patterns.
      Transformation from the parotid ductal epithelium to the tumor cells is evident.
      Foci of foreign-body reactions against keratin materials were present.
      Immunoreactivities for cytokeratins reconfirmed the nature of squamous
      differentiation of the tumor cells. Ki-67-positive cells were confined along the
      outer basal layer of the tumor epithelium. Tests for alpha-smooth muscle actin
      and S-100 protein were completely negative. Both patients had no evidence of
      recurrence 3 and 2 years after subtotal parotidectomy, respectively, without any
      additional therapy. We believe that this lesion represents a benign cystic
      neoplasm rather than a malignant tumor or pseudoneoplastic metaplastic condition.
      It is important to recognize that this peculiar benign tumor does originate from
      the salivary gland.

PMID- 12218220
TI  - Fixed drug eruption: easily overlooked but needing new respect.

PMID- 12218221
TI  - Is there a reproductive safety risk in male patients treated with acitretin
      (neotigason/soriatane?
AB  - Review of preclinical data including genotoxicity assays and a male rat
      reproduction toxicology study demonstrates that acitretin (Neotigason)/Soriatane)
      does not affect the reproductive outcome in naive females mated with treated
      males. Prospective studies of teratogenic risk or impairment of fertility cannot
      be ethically conducted in humans. However, it is highly unlikely that any fetal
      malformation could be induced by an ejaculate containing traces of acitretin.
      Indeed, worldwide postmarketing surveillance has not revealed any cases of
      retinoid embryopathy associated with paternal treatment with acitretin. Birth
      defects seen in pregnancies fathered by male acitretin patients were all events
      expected to occur in the general population at known frequencies. In conclusion,
      therefore, available data do not appear to indicate any reproductive safety risk
      due to paternal treatment with acitretin.

PMID- 12218222
TI  - Kenogen. A new phase of the hair cycle?
AB  - BACKGROUND: A novel phenomenon has been described by the phototrichogram: the
      emptiness of the follicle after teloptosis. We called this phenomenon kenogen,
      from the Greek kappaepsilonnuovarsigma, 'empty'. OBJECTIVE: To describe the
      kenogen phase in its details. METHODS: Analysis of the existing literature.
      RESULTS: The original observation in 2 women was confirmed in 10 balding and non
      balding males studied for 14 years in whom kenogen lasted about 4 months
      increasing up to about 7 months and affecting 80% of all hair cycles. In 2 women
      with progressing androgenetic alopecia studied for 2 years, kenogen involved 22%
      of the hair follicles, lasting from 3 months to 1 year. In a prepubertal boy
      studied for 1 year, it involved 8% of hairs and lasted about 2 months.
      CONCLUSION: During kenogen, the hair follicle rests physiologically, but duration
      and frequency are greater in androgenetic alopecia, possibly accounting for
      baldness. In addition to the classical cycle, the hair follicle may follow an
      alternative route during which the telogen phase, not accompanied by a coincident
      new early anagen, ends with teloptosis leaving the follicle empty.

PMID- 12218223
TI  - Evaluation of soluble Fas ligand as a serological marker for melanoma.
AB  - BACKGROUND: Fas ligand (Fas-L), which is expressed by melanoma cells, can be
      cleaved from cell membranes and become soluble (soluble Fas-L, sFas-L). No
      previous study examined sFas-L levels in patients affected with all clinical
      stages of melanoma. OBJECTIVE: To investigate if sFas-L can be considered a
      serological marker for melanoma. METHODS: Serological sFas-L values in 114
      patients with melanoma and 25 controls were measured by using ELISA. RESULTS:
      sFas-L values in patients were not significantly higher than in controls. They
      were not significantly different, moreover, when patient groups belonging to
      different clinical stages were compared with the control group. Two patients
      affected with distant metastases had the highest sFas-L values. CONCLUSION: sFas
      L cannot be considered, within the limits of this study, as a serological marker
      for the detection of melanoma. Further studies are needed to evaluate whether
      sFas-L can be used as a marker for disease progression and/or prediction of
      therapy outcome.

PMID- 12218224
TI  - Cytokine pattern in blister fluid and sera of patients with pemphigus.
AB  - BACKGROUND: Pemphigus is a chronic auto-immune blistering disease with four main
      variants, i.e. pemphigus vulgaris (PV), foliaceus (PF), erythematosus (PE) and
      vegetans. The common histological feature of this disease is acantholysis.
      OBJECTIVE: The aim of this study was to compare levels of some cytokines in
      blister fluid and sera of patients with pemphigus, using as control blister fluid
      of patients with bullous pemphigoid (BP) and bullous contact dermatitis (BCD).
      METHODS: Using an immuno-enzymatic assay (ELISA), we tested 16 sera and 6 blister
      fluids of patients with various forms of pemphigus (13 with PV, 1 with PF, 2 with
      PE), the sera of 16 healthy control subjects, 5 blister fluids of patients with
      BP and 5 blister fluids of patients with BCD, for the presence of some cytokines
      (IL-10, IL-8 and IFN-gamma). Intercellular antibodies were searched for and
      titred; desmoglein 1 and 3 antibody levels were independently evaluated to
      compare them with the severity of both cutaneous and oral involvement. RESULTS:
      The levels of IL-10 in the sera of patients with pemphigus were below the
      detection limits. IL-8 was significantly increased only in 4 samples of sera from
      pemphigus patients compared with controls, while IFN-gamma was detected at low
      levels in almost all patients compared with sera of controls. The cytokine levels
      in blister fluid of patients with pemphigus were significantly higher than in the
      sera. There was a difference between the expression of cytokines in blister fluid
      of control patients with BP and BCD compared with those of pemphigus patients.
      CONCLUSION: This report discusses the anti-inflammatory role played by IL-10 in
      the chronic form of pemphigus and the hypothesis of a possible role of IL-8 in
      neutrophil and lymphocyte-monocyte recruitment.

PMID- 12218225
TI  - Hyaluronate accumulation and decreased CD44 expression in perifollicular solitary
      cutaneous myxoma.
AB  - BACKGROUND: Myxomas are rare cutaneous tumors which may be solitary or associated
      with Carney's complex, NAME or LAMB syndromes. The mucinous material which
      constitutes the stroma of cutaneous myxomas is predominantly composed of
      hyaluronate (HA), the major component of the extracellular matrix. CD44 is a
      polymorphic integral membrane glycoprotein which serves as the principal cell
      surface receptor for HA. OBJECTIVE AND METHODS: Here we present 2 cases of
      solitary cutaneous myxomas displaying microscopically a perifollicular
      localization, in which we explored the nature of the accumulated mucinous
      material by colloidal iron and HA-binding protein stainings, as well as the
      epidermal expression of CD44 protein by immunohistochemistry. RESULTS: We show
      that HA is accumulated in the stroma of the cutaneous myxoma lesions and that the
      protein expression of CD44 in the keratinocytes of the trichofolliculoma-like
      epithelial buds projecting from the hair follicle centering these lesions is
      significantly decreased. CONCLUSIONS: Our results suggest that a decrease in CD44
      expression in follicular epithelial proliferations may be correlated with an
      abnormal HA accumulation in cutaneous myxoma.

PMID- 12218226
TI  - General practitioners' accuracy in diagnosing skin cancers.
AB  - BACKGROUND: The incidence of both melanoma and nonmelanocytic skin cancers has
      risen dramatically during the past decades, skin cancer becoming an important
      public health concern. OBJECTIVE: The purpose of this study was to assess the
      ability of general practitioners (GPs) in the early diagnosis of skin cancers,
      their correct differential diagnosis of benign lesions and their accuracy in the
      choice of the treatment. METHODS: A multiple-choice questionnaire regarding 7
      cases (with 4 figures) were sent to 625 GPs to evaluate their diagnostic
      abilities. CONCLUSIONS: The results indicate that many GPs are not confident in
      their ability to recognize the most common skin cancers, and knowledge
      deficiencies were identified.

PMID- 12218227
TI  - Novel spot-like pigmentary pattern detected by high-resolution epiluminescence
      microscopy.
AB  - BACKGROUND: Epiluminescence light microscopy (ELM) can be improved with enhanced
      optical resolution. OBJECTIVE: High-resolution ELM was performed by placing a
      standard light microscope on the skin surface for visualization of further
      details. METHODS: 25 melanocytic nevi and 14 melanomas with a globular pattern
      were investigated and examined histologically. RESULTS: A new spotty substructure
      was detected, namely individual pigmented spots of 5-10 micro m in diameter
      located within peripheral brown globules. Clinicopathologic correlation showed
      these spots to correspond with individual pigmented melanocytes (IPMs) within
      nests of melanocytes. IPMs were seen in 9/25 melanocytic nevi and in none of 14
      melanomas. CONCLUSION: Their origin may be a physiologic, UV-dependent pigment
      induction suggesting that they may represent a benign ELM pattern.

PMID- 12218228
TI  - Imiquimod, a topical immune response modifier, in the treatment of cutaneous
      metastases of malignant melanoma.
AB  - BACKGROUND: Imiquimod 5% cream (Aldara, a novel topical immune response modifier,
      has been approved for the topical treatment of anogenital HPV-induced warts. In
      addition, several studies have demonstrated antitumoral activity in solar
      keratoses, superficial basal cell carcinomas and Bowen's disease. AIM: Given the
      convincing therapeutic results of imiquimod when used for treating selected types
      of epithelial skin cancer, we became interested to study imiquimod as an adjuvant
      for treating cutaneous metastases of malignant melanoma. METHODS: Three patients
      with multiple, i.e. more than 15, cutaneous in-transit metastases of malignant
      melanoma in unilateral localization on the leg were treated topically with
      imiquimod 5% cream. RESULTS: Twice daily application under occlusive conditions
      for a period of 21-28 weeks resulted in >90% regression of cutaneous metastases
      in 2 patients. The third patient showed marked response only when topical
      imiquimod was intermittently supplemented by intralesional interleukin (IL)-2 for
      2 weeks. Unwanted side effects were mild in all patients. CONCLUSION: Overall,
      imiquimod as a single agent or in combination with intralesional IL-2 may be a
      promising immunomodulatory compound for the adjuvant topical treatment of
      patients with multiple cutaneous metastases of malignant melanoma.

PMID- 12218229
TI  - Topical 5% imiquimod long-term treatment of cutaneous warts resistant to standard
      therapy modalities.
AB  - BACKGROUND: Long-lasting cutaneous warts may represent an unbearable stigma to
      patients and therefore pose a singular challenge for the physician. Generally,
      these warts are induced by human papillomavirus (HPV) 2, HPV-27 or HPV-57.
      OBJECTIVES: The present study was conducted to evaluate the efficacy and safety
      of long-term treatment with imiquimod 5% cream applied to long-lasting (mean
      duration 6.3 years) common warts, which had been resistant to previous
      therapeutic interventions. PATIENTS AND METHODS: Imiquimod cream was self-applied
      by the patients twice daily. Assessment of response and occurrence of side
      effects was performed every 4 weeks until clinical cure or up to a maximum of 24
      weeks. A total of 37 patients were recruited. RESULTS: 31 out of 37 patients
      completed the treatment. 10 out of 37 patients experienced a total clearance of
      their warts (27%). The mean duration to clearance was 19.2 weeks. 18 patients
      (49%) showed a reduction of more than 50% and 5 patients (14%) a reduction of
      less than 50%. CONCLUSION: Our data demonstrate that the long-term topical
      application of imiquimod 5% cream is an effective treatment for otherwise therapy
      resistant cutaneous warts without causing any meaningful side-effects.

PMID- 12218230
TI  - A retrospective study of the effect of long-term topical application of
      retinaldehyde (0.05%) on the development of actinic keratosis.
AB  - BACKGROUND: The role of topical retinoids on photocarcinogenesis is still
      unclear. Retinaldehyde is a natural metabolite of vitamin A used as a cosmetic
      product. Its effect on actinic keratoses has not been studied to date. OBJECTIVE:
      To study the incidence of actinic keratoses during long-term application of
      retinaldehyde in order to evaluate a possible chemoprophylactic effect. METHODS:
      We conducted a retrospective study on 61 patients who had applied retinaldehyde
      on photoexposed body areas for a period ranging from 6 to 142 months. We counted
      the total number of actinic keratoses and cutaneous tumors that appeared over the
      time of exposure to retinaldehyde. RESULTS: The epidemiological characteristics
      of actinic keratoses were not modified by the application of retinaldehyde.
      Irregular application as compared to regular application of retinaldehyde was not
      associated with a change in the risk of actinic keratoses, suggesting that
      continuous use is not associated per se with a higher risk of actinic keratoses.
      CONCLUSION: With the statistical power limitation of this study, retinaldehyde
      applied alone does not appear to have prophylactic effects on the development of
      actinic keratoses. The design adopted is feasible to study the safety of cosmetic
      products applied for a long period of time.

PMID- 12218231
TI  - The antibacterial activity of topical retinoids: the case of retinaldehyde.
AB  - BACKGROUND: Retinoids such as retinoic acid (RA), retinol (ROL) and retinaldehyde
      (RAL) are currently used in many formulations and indications ranging form acne
      to skin aging. Most if not all their pharmacological activities occur through
      binding to nuclear receptors with subsequent modulation of the activities of
      several genes. Little attention has been given to the many other potential
      actions on the surface of the skin. AIM: To analyse the potential anti-infective
      activities of topical ROL, RAL and RA. METHODS: Microbial minimal inhibitory
      concentrations (MIC) of ROL, RAL and RA were determined by a microdilution method
      on reference strains including Staphylococcus aureus, Staphylococcus epidermidis,
      Micrococcus flavus, Propionibacterium acnes, Micrococcus luteus, Enterococcus
      faecium, Staphylococcus hominis, Escherichia coli, Pseudomonas aeruginosa,
      Candida albicans and 133 clinical strains including methicillin-resistant S.
      aureus, methicillin-sensitive S. aureus, coagulase-negative Staphylococcus,
      Streptococcus group B, Enterococcus faecalis, vancomycin-resistant E. faecalis,
      vancomycin-resistant E. faecium and Pseudomonas/Klebsiella. In two clinical
      trials in healthy human volunteers, skin bacterial densities were evaluated in
      samples obtained with the cylinder scrub method: (1). 2 and 5 h after a single
      application of 0.05% RAL or vehicle on the forearm and (2). in a single-blind
      randomized study where 0.05% RAL or vehicle were applied daily for 2 weeks on the
      forehead of 22 volunteers. Paired results from treated (or vehicle) and untreated
      areas were analysed. RESULTS: Of the three retinoids tested, only RAL showed a
      significant in vitro antibacterial activity; this activity was found against
      reference strains of gram-positive bacteria like S. aeureus, Micrococcus spp. or
      P. acnes. No activity was found against gram-negative bacteria. These results on
      reference strains were confirmed on 133 clinical isolates. MIC(50) and MIC(90)
      values for RAL were 8 and 16 mg/l, respectively, for methicillin-sensitive S.
      aureus and 4 and 8 mg/l for methicillin-resistant S. aureus. The two in vivo
      studies showed that areas treated with RAL had a significant decrease in the
      bacterial counts. In the forehead study, the median decrease was 10(2) log/cm(2)
      for P. acnes and 10(1.8) log/cm(2) for staphylococci. No resistant bacteria were
      found after 2 weeks of topical use. Preliminary results suggest that the
      antibacterial effect of RAL is due, in part, to the aldehyde group in the lateral
      chain, since non-retinoid pseudo-analogues of the chain, like citral and hexenal,
      showed a similar antibacterial activity. CONCLUSION: We have shown that RAL
      differs from parent natural retinoids such as ROL and RA in demonstrating
      significant antibacterial activities upon topical use. This activity is likely
      due to the aldehyde group in the isoprenoic lateral chain, which illustrates the
      potential bifunctional properties of some retinoids.

PMID- 12218232
TI  - Trauma-localized fixed drug eruption: involvement of burn scars, insect bites and
      venipuncture sites.
AB  - Little is known about why fixed drug eruption (FDE) lesions initially appear in a
      particular area of predilection. We describe 2 cases in whom the FDE lesions
      initially appeared exactly at the same sites of a previous trauma, such as burn
      scars and insect bites, and at a venipuncture site. The interval between the
      original trauma and the initial onset of FDE ranged from 2 days to 22 years.
      These 'trauma-localized' FDE lesions are helpful for our understanding of the
      mechanisms of FDE and other skin diseases, which often appear in their particular
      areas of predilection, a finding known as 'recall phenomenon'.

PMID- 12218233
TI  - Simultaneous presentation of silicone and silica granuloma: a case report.
AB  - We report a case of a 45-year-old woman who presented a simultaneous foreign-body
      granuloma reaction to silicone in her face and to silica in the elbow and knee.
      The patient had received silicone injections in her face 7 years earlier and had
      suffered a motorcycle accident when she was young. Changes suggestive of silicone
      were observed in the biopsy obtained from the face, and silica was detected in
      the biopsy taken from the elbow, confirmed by polarized light and X-ray
      microanalysis. The presence of polarizable foreign matter in cutaneous
      epithelioid granulomas should alert to the diagnosis of sarcoidosis.

PMID- 12218234
TI  - Papulonodular lichenoid and pseudolymphomatous reaction at the injection site of
      hepatitis B virus vaccination.
AB  - Immunization with the hepatitis B virus (HBV) is effective and safe with an
      estimated incidence of adverse reactions, either local or systemic, of less than
      0.1%. Cutaneous side effects are rare and include lichen planus (LP) and
      lichenoid reactions. We report the case of a 21-year-old female, in whom a
      persistent, papulonodular lesion developed at the site of the injection, 6 weeks
      after the second dose of the HBV. Histological examination revealed lichenoid and
      pseudolymphomatous features. In addition, sensitization to thiomersal, a vaccine
      constituent, was documented by patch testing. The association of LP with chronic
      liver disease is well established. Furthermore, less than 20 cases of lichen or
      lichenoid reactions, following HBV vaccination, have been reported. Although
      several arguments have been presented, it is still debated whether there is a
      causal association or the occurrence of LP following HBV vaccination is a simple
      coincidence. It has been speculated that a T-cell-mediated, graft-versus-host
      like reaction, triggered by a sensitizing protein, is directed against
      keratinocytes expressing an epitope of hepatitis B surface antigen or a similar
      epitope. Our case may represent a localized lichenoid reaction to HBV
      vaccination, a local reactive hyperplasia or a persisting delayed
      hypersensitivity reaction to a vaccine constituent. This is the first case of a
      local lichenoid reaction at the injection site of the HBV vaccine, providing
      further documentation for a causal association linking the HBV vaccine with LP.

PMID- 12218235
TI  - Oral lichenoid reaction to imatinib (STI 571, Gleevec).
AB  - Imatinib or STI 571 is a phenylaminopyrimidine derivative and a member of a new
      class of drugs known as signal transduction inhibitors. These compounds
      specifically inhibit the proliferation of v-abl- and bcr-abl-expressing cells and
      have recently been approved as treatment for chronic myeloid leukaemia (CML).
      Results have been promising, and imatinib may well be the best single agent for
      the treatment of CML in the near future. Here we report an erosive oral lichenoid
      eruption confined to the buccal mucosa and dorsum of the tongue which appeared 12
      weeks after commencement of imatinib in a 72-year-old woman with CML. The
      histology was consistent with a lichenoid drug eruption. The lesions resolved
      upon withdrawal of the drug. To our knowledge, this is the first reported
      lichenoid reaction to imatinib, and in the setting of CML it must be
      differentiated from idiopathic lichen planus, paraneoplastic pemphigus and graft
      versus-host disease.

PMID- 12218236
TI  - Pityriasis rosea associated with imatinib (STI571, Gleevec).
AB  - A tyrosine kinase inhibitor (STI571, Gleevec) has recently been applied in the
      treatment of chronic myeloid leukemia. We present the first reported case of
      pityriasis rosea occurring as a reaction to Gleevec in a woman with blast crisis
      of this disorder. It is suggested that although coincidental, this exanthem may
      be due to this agent.

PMID- 12218237
TI  - Eruptive multiple lentigo-maligna-like lesions in a patient undergoing
      chemotherapy with an oral 5-fluorouracil prodrug for metastasizing colorectal
      carcinoma: a lesson for the pathogenesis of malignant melanoma?
AB  - Induction of multiple eruptive dermal and atypical melanocytic naevi has
      frequently been reported in children with malignant haematological diseases and
      chemotherapy-induced immunosuppression. This is the first report of an adult
      patient to develop multiple eruptive melanocytic skin lesions while undergoing
      chemotherapy with an oral 5-fluorouracil prodrug for metastasizing cancer. Our
      observation adds further evidence to the link between systemic (iatrogenic or
      intrinsic) immunosuppression and the induction of melanocyte proliferation and
      transformation.

PMID- 12218238
TI  - Cytotoxic mycosis fungoides evolving from pityriasis lichenoides chronica in a
      seventeen-year-old girl. Report of a case.
AB  - Pityriasis lichenoides chronica and its acute form, pityriasis lichenoides et
      varioliformis acuta, are skin diseases of unknown origin, that probably represent
      a hypersensitivity reaction to an infective agent. Pityriasis lichenoides is
      often a benign disorder but, because of the presence of a clonal T cell
      population detected both in the chronic and acute forms, some authors have
      suggested that it may belong to the group of primary cutaneous T cell lymphomas.
      Although various studies have clearly documented no significant association
      between pityriasis lichenoides and malignant lymphomas, cases of long-standing
      pityriasis lichenoides evolving into mycosis fungoides have been described.
      Herein we report the case of a girl suffering from pityriasis lichenoides since
      the age of 11 years, subsequently developing a CD45RO+, CD8+, TIA-1+ mycosis
      fungoides.

PMID- 12218239
TI  - Meyerson phenomenon within a nevus flammeus. The different eczematous reactions
      within port-wine stains.
AB  - Only few reports about eczematous reactions overlying nevi flammei exist. All of
      them were observed in children. The description of an eczematous reaction within
      a congenital nevus flammeus on the left lower leg of a male adult gives reason to
      discuss this rare phenomenon. Eczema or inflammatory changes within a port-wine
      stain may mostly be a collision dermatosis with an atopic dermatitis, especially
      when they arise in children and are localized to the neck and face. When they are
      observed within a grossly visible vascular malformation, as for example in the
      Klippel-Trenaunay syndrome, they may have a pathogenesis similar to stasis
      dermatitis. In rare cases, an eczematous reaction within a nevus flammeus may be
      the result of genetic mosaicism and is interpreted as a variant of the so-called
      Meyerson phenomenon.

PMID- 12218240
TI  - Blister on a skin tag.

PMID- 12218241
TI  - Minocycline-induced lupus and autoimmune hepatitis: family autoimmune disorders
      as possible risk factors.

PMID- 12218242
TI  - Digital epiluminescence microscopy in nevi during pregnancy.

PMID- 12218243
TI  - An exceptional localization of angiokeratoma of fordyce on the glans penis.

PMID- 12218244
TI  - A lack of clinical correlation between the presence of HHV-8 DNA in PBMCs and
      staging of Kaposi's sarcoma.

PMID- 12218245
TI  - Monoclonal rearrangement of the T cell receptor gamma-chain in lichenoid
      pigmented purpuric dermatitis of gougerot-blum responding to topical
      corticosteroid therapy.
AB  - Lichenoid pigmented purpuric dermatitis of Gougerot-Blum belongs to a group of
      closely related disorders which are termed pigmented purpuric dermatoses. It
      clinically manifests itself with grouped lichenoid papules in association with
      purpuric lesions. We report a case of lichenoid pigmented purpuric dermatitis of
      Gougerot-Blum with a heavy band-like CD4-positive lymphocytic infiltrate and
      clonal rearrangements of the gamma-chain of the T cell receptors as detected by
      polymerase chain reaction/denaturing gradient gel electrophoresis. Monoclonal
      expansion of T cells in combination with certain histological features of mycosis
      fungoides (MF) might support a biological relationship between lichenoid
      pigmented purpuric dermatitis of Gougerot-Blum and MF. However, prompt clinical
      response to topical steroid therapy supports the benign clinical nature of our
      case.

PMID- 12218246
TI  - Periorbital oedema and erythema as a manifestation of discoid lupus
      erythematosus.
AB  - Periorbital oedema and erythema are a rare cutaneous manifestation of discoid
      erythematosus (DLE) which is well known to ophthalmologists but less to
      dermatologists. We report the case of a 74-year-old female patient with
      periorbital oedema and erythema. Since swelling of the eyelid is common in the
      dermatological practice, dermatologists should be aware of the differential
      diagnosis and its occurrence in patients with DLE.

PMID- 12218247
TI  - Papular elastorrhexis. report of five cases.
AB  - Papular elastorrhexis is a rare disorder that occurs predominantly during
      adolescence. We report 5 patients with asymptomatic white, nonfollicular, firm
      papules scattered over the trunk and extremities. Histologically, the papules
      demonstrate focal areas of collagen homogenization with decreased and fragmented
      elastic fibers. The clinical differential diagnosis includes papular acne scars,
      dermatofibrosis lenticularis disseminata (Buschke-Ollendorff syndrome), cutaneous
      collagenoma and nevus anelasticus, but histology clearly separates papular
      elastorrhexis from the other entities.

PMID- 12218248
TI  - Survey of dermatophyte infections in the Lausanne area Switzerland.
AB  - BACKGROUND: The dermatophytes are important in the Swiss medical environment
      since 5-10% of consultations in dermatology concern mycotic infections.
      OBJECTIVE: To obtain information about the prevailing species of dermatophytes in
      the south-west of Switzerland and their pattern of infection. METHODS: An
      analysis was made of the dermatophytes isolated in the Department of Dermatology
      at the University Hospital of Lausanne and from samples collected in private
      practices of Switzerland during an 8-year period (1993-2000). The total number of
      samples sent for mycological analysis was 33,725. RESULTS: 4,193 cultures
      revealed a dermatophyte. Trichophyton rubrum was the most frequently isolated
      species accounting for 62.5% of the strains followed by T. mentagrophytes (24.5%)
      and Microsporum canis (5.0%). Less frequent isolates included Epidermophyton
      floccosum, M. langeroni, M. gypseum, T. soudanense, T. violaceum, T. verrucosum,
      T. gourvili and T. tonsurans. Analysis of the localisation of the isolated fungi
      confirms that the dermatophyte species have a predilection for certain body
      areas. CONCLUSIONS: The relative frequencies of isolation of the dermatophyte
      species partially depending of the record of the different tinea vary from one
      country to another. Our study reveals the importance of T. rubrum and the
      appreciable frequency of M. canis in the Swiss autochthonous population and the
      apparition of new species with immigrants.

PMID- 12218249
TI  - Eosinophilic fasciitis (Shulman syndrome).
AB  - We report a case of a 30-year-old Caucasian patient with progressive sclerosis of
      the skin mainly on the upper limbs which was diagnosed as eosinophilic fasciitis
      (Shulman syndrome). Circulating antibodies against Borrelia burgdorferi were
      detected. The association of B. burgdorferi infection with eosinophilic fasciitis
      is discussed.

PMID- 12218250
TI  - Cutaneous larva migrans associated with Loffler's syndrome.
AB  - We describe a patient who was admitted to hospital after returning from a holiday
      in Thailand with coronary artery disease and ventricular tachycardia. As an
      incidental finding, the routine chest radiography showed migratory pulmonary
      infiltrates. A peripheral blood smear showed eosinophilia. Physical examination
      revealed multiple, slightly raised, erythematous, serpentine tracks on the
      buttocks. A clinical diagnosis of larva migrans was made, and the patient was
      treated with oral albendazole 400 mg on 5 consecutive days and a single dose of
      oral praziquantel 3600 mg. By the end of treatment, most of the cutaneous
      lesions, the pulmonary infiltrates and the peripheral eosinophilia had resolved.
      The final diagnosis was larva migrans associated with Loffler's syndrome.

PMID- 12218251
TI  - Multiple hyperkeratotic spicules and myeloma.
AB  - We report the case of a 58-year-old patient with multiple myeloma with a
      monoclonal gammopathy of the IgG type, who developed a striking eruption
      characterized by multiple hyperkeratotic spicules of the face, nose and scalp.
      Light-microscopic studies revealed a follicular orthohyperkeratosis, while direct
      immunofluorescence microscopy remained negative. Hence, our patient presented
      features characteristic of a rare distinctive disorder associated with an
      underlying paraprotein or multiple myeloma, paraneoplastic hyperkeratotic
      spicules.

PMID- 12218252
TI  - Generalised pustular psoriasis induced by cyclosporin a withdrawal responding to
      the tumour necrosis factor alpha inhibitor etanercept.
AB  - We report a 50-year-old male patient with a 15-year history of psoriasis
      including mutilating psoriatic arthritis, in whom the withdrawal of cyclosporin A
      induced a generalised pustular exacerbation and a aggravation of the joint
      condition. Two weekly injections of 25 mg of the tumour necrosis factor alpha
      inhibitor etanercept led to a rapid improvement of his psoriatic arthritis, as
      well as regression of the pustular eruption, while residual erythema was still
      present. The clinical response was reflected by an increase in circulating
      interleukin (IL) 10 and a decrease in IL-6 and IL-8 serum levels during
      treatment. We conclude that etanercept may be a safe and effective therapy not
      only in severe psoriatic arthritis, but also in cases of pustular rebound after
      withdrawal of immunosuppressive agents.

PMID- 12218253
TI  - Measurement of laminins in the cerebrospinal fluid obtained from patients with
      Alzheimer's disease and vascular dementia using a modified enzyme-linked
      immunosorbent assay.
AB  - We developed a new enzyme-linked immunosorbent assay (ELISA) system using
      antibodies against intact human laminin, laminin alpha(5)-chain, laminin beta(1)
      chain, laminin gamma(1)-chain and laminin alpha(1)-chain peptide (YFQRYLI). Using
      this ELISA, we measured the anti-laminin immunoreactivity levels in the
      cerebrospinal fluid (CSF) obtained from patients with Alzheimer's disease (AD),
      vascular dementia (VaD), and other disorders. The present study showed the levels
      of certain laminins in CSF to demonstrate significant differences in the chain
      levels in different dementias. The AD group showed a significantly lower level of
      anti-laminin gamma(1) immunoreactivity. The late-onset AD group showed
      significantly elevated anti-laminin alpha(1)-peptide (YFQRYLI) immunoreactivity
      levels in comparison with the early-onset AD group and controls. On the other
      hand, the VaD group showed significantly higher levels of anti-intact human
      laminin and anti-laminin beta(1) immunoreactivity. The assays of anti-laminin
      immunoreactivity levels in CSF provided an efficient sensitivity (85.0%) and
      specificity (93.7%) for the diagnosis of AD by using the ratio of tau to anti
      intact human laminin immunoreactivity levels. These results suggest that CSF
      laminin or its derivatives may correlate with the pathogenesis of AD and VaD, and
      the prevention of the proteolytic activity may be an effective therapeutic method
      for either preventing or slowing down the progression of AD. Furthermore, it was
      shown that performing ELISA for CSF laminins may prove to be useful for detecting
      the biological markers of AD and VaD.

PMID- 12218254
TI  - Interleukin 1 alpha gene polymorphism as a susceptibility factor in Alzheimer's
      disease and its influence on the extent of histopathological hallmark lesions of
      Alzheimer's disease.
AB  - We investigated the association of the interleukin 1alpha (IL1A) (-889) C/T
      polymorphism with Alzheimer's disease (AD) and with the extent of AD
      histopathological lesions, the senile/neuritic plaques (SPs/NPs) and
      neurofibrillary tangles. We evaluated 98 neuropathologically confirmed AD
      patients and 240 controls as well as 146 clinically diagnosed AD patients and 278
      controls but found no association of the IL1A C/T polymorphism with AD even after
      adjustment for the apolipoprotein E (APOE) genotype, gender or age. The extents
      of AD histopathological lesions were not influenced by the IL1A genotype except
      after exclusion of the APOE epsilon4 allele, when a trend towards more SPs/NPs
      was observed in AD patients with the IL1A C/C compared to patients with the T/T
      genotype. These results do not confirm previous studies which have indicated that
      the IL1A C/T polymorphism is a susceptibility factor for AD. However, the IL1A
      C/C genotype might be associated with the progression of SPs/NPs in AD patients,
      but the effect is weak and obscured by the APOE epsilon4 allele.

PMID- 12218255
TI  - Alzheimer disease - effect of continuous intracerebroventricular treatment with
      GM1 ganglioside and a systematic activation programme.
AB  - Five patients with the early-onset form of Alzheimer disease (AD) received GM1
      ganglioside by continuous injection into the frontal horns of the lateral
      ventricles for a period of 12 months. The optimal GM1 dose varied between 20 and
      30 mg/24 h. The patients were trained twice a week for 4-5 h with an individually
      designed cognitive programme, which included the use of a word processor.
      Neurological, neuropsychological, psychiatric and neurochemical examinations were
      performed a week before surgery and on days 30, 90, 180, 270 and 365 after
      surgery. The cerebrospinal fluid levels of the monoamine metabolites homovanillic
      acid and 5-hydroxyindoleacetic acid and the neuropeptide somatostatin increased.
      The regional cerebral blood flow showed a tendency to increase. The progression
      of deterioration was stopped, and motor performance and neuropsychological
      assessments improved. The patients became more active and felt safer in relation
      to other people and performing various activities. They had improved reading
      comprehension and a better feeling for language. They were able to write reports
      and short letters on a word processor. When interviewed at the end of the study,
      all 5 patients stated that they felt better, and their relatives reported that
      they had regained integrity and their joie de vivre.

PMID- 12218256
TI  - Incidence of pre- and poststroke dementia: cracow stroke registry.
AB  - BACKGROUND AND PURPOSE: Dementia after stroke may be caused by vascular lesion,
      but preexisting degenerative changes can also influence its development. After
      stroke, the patients with coexisting Alzheimer-type pathology need appropriate
      treatment. The aim of the study was to evaluate the frequency of prestroke and
      new- onset dementia in stroke patients. METHODS: We evaluated prestroke dementia
      in 250 patients with ischemic or hemorrhagic stroke using the Informant
      Questionnaire on Cognitive Decline in the Elderly (IQCODE). Poststroke dementia
      was assessed in 220 patients 3 months after stroke by means of the
      neuropsychological tests and/or IQCODE. The DSM-IV definition of dementia was
      used. RESULTS: Dementia after stroke was found in 31.4% of stroke patients.
      Twelve percent of stroke patients had a significant impairment of cognitive
      functions detected by the IQCODE on admission suggesting prestroke dementia. When
      we excluded the patients with recurrent stroke, the incidence of pre- and
      poststroke dementia was 9.3 and 21.2%, respectively. CONCLUSION: About one tenth
      of stroke patients have preexisting dementia.

PMID- 12218257
TI  - Complex cognitive disruption in motor neuron disease.
AB  - We describe 14 patients having been diagnosed as suffering from motor neuron
      disease (MND). These patients underwent a detailed and sequential
      neuropsychological evaluation, with particular care of neurolinguistic
      assessment. Their results have been compared to those obtained by a group of
      healthy volunteers. The most obvious disclosure was the finding of 4 cases of
      frontal dementia in the MND group. Apart from that, we demonstrated subtle though
      evident frontal disruption signs, evidenced by an alteration in language
      planning, language comprehension, morphosyntactic operations, planning, attention
      deficit, and abstract reasoning disturbances which got worse during the 15 months
      of follow-up in all the other subjects. We suggest that a specific and sensitive
      neurolinguistic and neuropsychological test battery could detect signs of
      disruption of cognition present even in the sporadic form of MND. We discuss the
      results with a review of the literature.

PMID- 12218258
TI  - Lack of association between plasma homocysteine and inflammation in
      psychogeriatric patients.
AB  - BACKGROUND/OBJECTIVES: In previous studies we observed a high incidence of
      elevated plasma homocysteine (tHcy) concentrations in psychogeriatric patients.
      Plasma tHcy is increased in folate deficiency. Folates are sensitive to oxidative
      stress. Oxidative stress, caused by inflammatory processes, could represent an
      endogenous reason for folate deficiency, even when the dietary intake of the
      vitamin is within the recommended range. It has been suggested that oxidative
      stress rather than insufficient folate intake causes hyperhomocysteinemia in
      different forms of psychogeriatric diseases. In the present study we investigated
      the association between plasma tHcy and C-reactive protein (CRP), a sensitive
      marker for inflammation, in psychogeriatric patients. METHODS: Plasma tHcy, its
      main determinants, and CRP were measured in plasma and serum of 132
      psychogeriatric patients (53 males and 79 females, mean age 75 +/- 12 years).
      RESULTS: In the psychogeriatric patients, plasma tHcy was elevated and blood
      folate and serum creatinine were lower than in control subjects, whereas serum
      CRP concentrations did not differ significantly. We also subdivided the
      psychogeriatric patients into different diagnosis groups, yet there were no
      differences in serum CRP concentrations in these groups compared with age-matched
      control groups. There was a significant correlation between plasma tHcy and serum
      CRP (rho = 0.19, p < 0.05). A stepwise multiple regression analysis including
      serum CRP, age, blood folate, serum cobalamin, serum methylmalonic acid and serum
      creatinine showed that only blood folate (p < 0.001), age (p < 0.001), serum
      creatinine (p < 0.001), serum cobalamin (p < 0.001), and serum methylmalonic acid
      (p < 0.001) independently predicted plasma tHcy concentration. Thus CRP
      concentration was not an independent predictor of plasma tHcy. CONCLUSION: The
      present study did not show any association between inflammatory status and plasma
      tHcy concentration in psychogeriatric patients.

PMID- 12218259
TI  - Plasma levels of Abeta42 and Abeta40 in Alzheimer patients during treatment with
      the acetylcholinesterase inhibitor tacrine.
AB  - Deregulation of amyloid precursor protein (APP) processing with increased
      production of amyloid beta-peptide (Abeta) is considered to be a key pathogenic
      event in Alzheimer's disease (AD). It has been suggested that stimulation of the
      muscarinic M(1) receptor subtype affects APP processing and leads to a change in
      Abeta concentration. To test the hypothesis that treatment with a cholinesterase
      inhibitor could change the levels of Abeta in plasma, we measured Abeta42 and
      Abeta40 plasma levels in AD subjects before tacrine treatment and at weeks 2 and
      6 of treatment. Treatment with tacrine had no statistically significant effect on
      plasma Abeta42 and Abeta40 either at 2 weeks or at 6 weeks of administration
      compared to baseline levels. Plasma Abeta42 and Abeta40 levels showed large
      subject-to-subject variation but small variation within the same patient over the
      3-sample interval. After 2 weeks of treatment with tacrine, there was a strong
      negative correlation between tacrine concentration and levels of Abeta42 (r = 
      0.64; p = 0.01) and Abeta40 (r = -0.55; p = 0.04). However, after 6 weeks there
      was no correlation between plasma concentrations of tacrine and Abeta42 (r =
      0.33; p = 0.34) or Abeta40 (r = -0.22; p = 0.54) levels in plasma. After 2 weeks
      of treatment with an acetylcholinesterase inhibitor, we found a correlation
      between higher drug concentrations and lower beta-amyloid levels. This might
      indicate an effect on APP metabolism with an increased alpha-cleavage. But after
      6 weeks of drug treatment, there was no obvious drug effect on beta-amyloid
      concentrations. This finding may indicate that compensatory mechanisms have
      started at 6 weeks and that no long-term effect on key pathological features in
      AD is to be expected by an inhibition of acetylcholinesterase.

PMID- 12218260
TI  - Cerebral amyloid angiopathy, white matter lesions and Alzheimer encephalopathy -
      a histopathological assessment.
AB  - To test the hypothesis that the cerebral amyloid angiopathy (CAA) of Alzheimer's
      disease (AD) is quantitatively associated with white matter lesions (WML), the
      brains of 63 demented patients exhibiting varying degrees of Alzheimer
      encephalopathy (AE) were examined, along with those of 10 nondemented control
      cases. The ratio of amyloid-positive to amyloid-negative vessels in the
      leptomeninges of the frontal pole from each patient was calculated subsequent to
      microscopical examination, and the severity of WML was graded according to
      previously published criteria. In AD cases without a significant component of
      vascular dementia, the level of CAA was found to correlate with the degree of WML
      diagnosed and graded by neuropathology. Neither age nor severity of AE correlated
      significantly with WML. There may be several reasons for the conflicting results
      of this study vis-a-vis earlier investigations; the roles played by different
      methods of staining, CAA quantitation and patient subgroup selection are also
      discussed.

PMID- 12218261
TI  - Effect of physical activity on the pharmacokinetics of ceftazidime in mice.
AB  - BACKGROUND: The aim of the present work was to assess comparatively the
      pharmacokinetic profile of ceftazidime (CAZ) in trained and non-trained mice.
      METHODS: The study was performed on 256 mice divided at random into four groups:
      long-term physically trained mice with (E1a) and without (E1b) physical activity
      prior to the administration of CAZ, and untrained mice with (E2a) and without
      (E2b) physical activity prior to the administration of the antibiotic. CAZ was
      administered intramuscularly (25 mg/kg) to all mice, and blood samples were
      obtained at different time points. The plasma concentrations of CAZ were
      determined by HPLC and analyzed by non-compartmental models. RESULTS: The area
      under the curves in groups E1a and E2a (27.3 and 22.9 microg x ml(-1) x h,
      respectively) were different compared to the other groups [(E1b) = 11.1 and (E2b)
      = 15.6 microg x ml(-1) x h; p < 0.05]. Differences were observed between the
      concentration-time of CAZ in E1a compared to E1b, E1a versus E2a, E1a versus E2b,
      E1b versus E2a and E1b versus E2b (p < 0.05). CONCLUSION: Physical activity
      performed prior to CAZ administration modified the pharmacokinetic profile of the
      drug administered to mice.

PMID- 12218262
TI  - Comparative study of antimicrobial resistance of Pseudomonas aeruginosa strains
      isolated from patients of Caracas and Asuncion in a 4-year-period.
AB  - The antimicrobial resistance of Pseudomonas aeruginosa to beta-lactams,
      aminoglycosides and ciprofloxacin was investigated in two Latin American
      hospitals, one in Venezuela and the other in Paraguay. The resistance of P.
      aeruginosa was investigated in 1,481 clinically isolated strains, 988 from
      Asuncion and 493 from Caracas, collected between 1996 and 1999. Susceptibility
      was assessed by the disk diffusion method according to the National Committee for
      Clinical Laboratory Standards. 11.4% were resistant to cefoperazone, 11.4% to
      ceftazidime, 12.8% to piperacillin, 13.6% to amikacin, 18.2% to gentamicin, 11.1%
      to ciprofloxacin, and 6.7% to imipenem. There were significant differences in
      resistance patterns between isolates from Asuncion and Caracas. Resistance was
      higher in Caracas. Despite similar antibiotic usage policies and other measures,
      differences in the resistance patterns of P. aeruginosa are evident in this
      study. The clinical and therapeutic implications of this resistance suggest the
      need to maintain surveillance in local settings, especially in developing
      countries such as Venezuela and Paraguay.

PMID- 12218263
TI  - Antimicrobial action of Nitens mouthwash (cetyltrimethylammonium naproxenate) on
      multiple isolates of pharyngeal microbes: a controlled study against
      chlorhexidine, benzydamine, hexetidine, amoxicillin, amoxicillin-clavulanate,
      clarithromycin, and cefaclor.
AB  - BACKGROUND: Acute oropharyngeal and respiratory tract infections are due to a
      wide spectrum of microorganisms. The aim of this study was to compare and
      evaluate the in vitro activity of four antiseptics (cetyltrimethylammonium
      naproxenate, chlorhexidine, benzydamine, hexetidine) to four antibiotics
      (amoxicillin, amoxicillin-clavulanate, clarithromycin, cefaclor) on strains of
      Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and
      Streptococcus pneumoniae. METHODS: Susceptibility tests were performed on 90,
      aerobic and anaerobic, bacterial strains, isolated from nasopharyngeal swabs and
      sputum. Minimum inhibitory concentrations (by microdilution) and minimum
      bactericidal concentrations were determined and compared. RESULTS: Our selected
      panel of bacteria was highly susceptible to the antiseptics, particularly to
      chlorhexidine and naproxenate, even more so than two of the most frequently used
      antibiotics. Data were statistically significant (p < 0.005). CONCLUSIONS: In
      view of their bactericidal and anti-inflammatory properties, these antiseptics
      may be effective in controlling the transitory colonization of the oral cavity by
      microbes that cause or worsen disease in patients with mild infections.

PMID- 12218264
TI  - Presence of mec genes and overproduction of beta-lactamase in the expression of
      low-level methicillin resistance among staphylococci.
AB  - Detection of methicillin-resistant staphylococci is critical for the management
      of infected patients in the hospital. A total of 55 nonreplicated clinical
      isolates of staphylococci (31 Staphylococcus aureus and 24 coagulase-negative
      staphylococci; CNS) collected during a one-year period and expressing low-level
      resistance to methicillin (oxacillin MIC of 2-4 mg/l for S. aureus and 0.5-4 mg/l
      for CNS) were studied. mec determinants and overproduction of beta-lactamase were
      investigated and pulsed-field gel electrophoresis (PFGE) was applied as a typing
      method. Twenty-four S. aureus isolates and 19 CNS carried the mecA gene. The
      presence of mecR1/mecI and blaR1/blaI genes correlated with the expression of low
      level methicillin resistance in CNS. Four mecA-negative isolates (2 S. aureus and
      2 CNS) overproduced beta-lactamase. PFGE revealed the presence of 2 major clonal
      types in mecA-positive S. aureus isolates, and 3 in CNS. Low-level methicillin
      resistance of staphylococci is correlated with the presence of the mecA gene and
      overproduction of beta-lactamase.

PMID- 12218265
TI  - Postantibiotic effect of meropenem and ciprofloxacin in the presence of 5
      fluorouracil.
AB  - BACKGROUND: The postantibiotic effect (PAE) of meropenem and ciprofloxacin was
      studied in the presence of the antineoplastic agent 5-fluorouracil (5-FU). The
      purpose of the study was to investigate whether the PAEs of the combinations
      differed from the PAEs of the antibiotics alone. METHODS: The PAEs of the
      combinations of 5-FU plus meropenem or ciprofloxacin were determined with viable
      counts against four reference strains of Staphylococcus aureus, Staphylococcus
      epidermidis, Pseudomonas aeruginosa, Escherichia coli and two clinical isolates
      of S. epidermidis. The results were compared with the PAEs of the antibiotics
      drugs and 5-FU alone. The gram-positive strains were tested for slime production,
      both alone and in the presence of 5-FU. RESULTS: Against two of the three tested
      strains of S. epidermidis, the combination of ciprofloxacin and 5-FU gave a
      synergistic prolongation of the PAE in comparison with the PAEs induced by the
      drugs alone. The combinations showed indifference against the other bacteria. The
      combination of meropenem and 5-FU had a synergistic PAE against one of the three
      tested strains of S. epidermidis and an additive effect against E. coli but
      showed indifference against the rest of the strains. CONCLUSIONS: The presence of
      5-FU did not influence the PAEs of the antibiotics against most of the tested
      strains, but caused a synergistic prolongation of the PAEs induced by
      ciprofloxacin and meropenem against some of the tested strains of S. epidermidis.
      5-FU inhibited slime production in the same S. epidermidis strains, which might
      have contributed to the longer PAE.

PMID- 12218266
TI  - Bcl-xL antisense oligonucleotides chemosensitize human glioblastoma cells.
AB  - BACKGROUND: Resistance to chemotherapy in glioblastoma has been linked to the
      expression of antiapoptotic Bcl-2 family members including Bcl-xL. METHODS: Bcl
      xL expression was specifically reduced in M059K glioblastoma cells with antisense
      oligonucleotides (ISIS 16009, ISIS 16967) as assessed by Western blotting.
      Induction of apoptosis by treatment with antisense oligonucleotides in
      combination with paclitaxel in cell culture was monitored by WST-1 assays and
      flow cytometric analysis. RESULTS: Antisense oligonucleotide-mediated reduction
      of Bcl-xL levels led to enhanced cytotoxicity in M059K cells when compared to the
      use of a mismatch control oligonucleotide (p < 0.001). A decreased threshold for
      the induction of apoptosis led to significantly enhanced cytotoxic responses to
      paclitaxel treatment in WST-1 assays (p < 0.001) and flow cytometric analyses.
      CONCLUSION: Combination treatment using Bcl-xL antisense oligonucleotides and
      paclitaxel may qualify as a promising strategy to ultimately improve the clinical
      outcome of glioblastoma.

PMID- 12218267
TI  - Interactions between the new cytotoxic drug CHS 828 and amiloride and mitomycin C
      in a human tumour cell line and in tumour cells from patients.
AB  - BACKGROUND: CHS 828 is a novel cyanoguanidine with cytotoxic properties which was
      recently shown to induce an early increase in extracellular acidification. This
      could hypothetically be exploited for combination with drugs interfering with, or
      being dependent on, pH for their effect. METHODS: The isobole method and the
      additive model were used to evaluate the combinations CHS 828-amiloride and CHS
      828-mitomycin C (MMC) in the lymphoma cell line U-937 GTB and in primary cultures
      of tumour cells from patients. RESULTS: Amiloride, which blocks the Na(+)/H(+)
      antiport, shifted the CHS 828 dose-response curve to the left in a synergistic
      manner according to the additive interaction model. MMC is a bioreductive drug
      with enhanced cytotoxicity at acidic pH. A lowering of pH induced by CHS 828
      would theoretically create a favourable environment for bioreduction of MMC. The
      interaction between these drugs was mainly classified as additive by both
      methods, but was synergistic at the highest effect level tested. In addition,
      there were sub-additive to synergistic interactions between CHS 838 and MMC in
      76% of the haematological samples tested. CONCLUSIONS: Circumstantial evidence
      indicated that the mechanisms for the interactions could be pH independent. Thus,
      the interaction between CHS 828 and amiloride was synergistic while the
      interaction between CHS 828 and MMC in tumour cells was at least additive.

PMID- 12218268
TI  - Phase I study of weekly irinotecan combined with weekly cisplatin in patients
      with advanced solid tumors.
AB  - BACKGROUND: Previous studies have reported a synergistic effect between
      irinotecan and cisplatin. We have conducted a phase I trial combining these
      agents to find the optimal dose of irinotecan in combination with a fixed dose of
      cisplatin. METHODS: Patients with advanced solid tumors, aged < or =75 years,
      performance status < or =2, and adequate organ function were enrolled in this
      study. They were treated at 4-week intervals with irinotecan plus 20 mg/m(2)
      cisplatin on days 1, 8, and 15. The starting dose of irinotecan of 40 mg/m(2) was
      escalated in 10 mg/m(2) increments until a maximum dose of 90 mg/m(2) was
      reached. RESULTS: The recommended dose for phase II studies is 90 mg/m(2) of
      irinotecan and 20 mg/m(2) of cisplatin on days 1, 8, and 15. Overall response to
      the chemotherapy was 35% (95% confidential interval, 19.2-54.6%). CONCLUSION:
      This combination seems to be active against lung cancer with acceptable toxicity.
      A phase II study is now ongoing.

PMID- 12218269
TI  - A pilot trial of combination cisplatin, 5-fluorouracil and interferon-alpha in
      the treatment of advanced esophageal carcinoma.
AB  - BACKGROUND/OBJECTIVES: Based on the synergistic effect between cisplatin and 5
      fluorouracil (5-FU), and between 5-FU and interferon-alpha, we conducted a trial
      to assess the response rate and toxicity of the combination of cisplatin, 5-FU
      and interferon-alpha in patients with advanced esophageal cancer. METHODS:
      Patients with locally advanced or metastatic squamous cell or adenocarcinoma of
      the esophagus were eligible. No prior chemotherapy or interferon were allowed.
      Patients received cisplatin 80 mg/m(2) on day 1, 5-FU 750 mg/m(2)/day by
      continuous intravenous infusion for 5 days, and interferon-alpha 5 x 10(6)
      units/m(2)/day by subcutaneous injection on days 1-5 of each cycle. Cycles were
      repeated every 21 days for a total of 6 cycles. RESULTS: Forty patients were
      enrolled. Median age was 57.5 years (range 30-70). 33 had squamous carcinoma and
      7 adenocarcinoma; 15 were male; the locoregional metastatic ratio was 1:39;
      median ECOG performance status was 2 (range 1-3). Grade 3-4 toxicities were:
      leukopenia (9 cases), thrombocytopenia (4), electrolyte imbalance (11), febrile
      neutropenia (11), vomiting (5), diarrhea (4), and mucositis (11). There were 3
      early deaths, most probably related to therapy. Five patients (13%) achieved a
      complete response and 17 (42%) achieved a partial response, yielding an overall
      response rate of 55%. Response rates for squamous and adeno histology were 61%
      and 29%, respectively. Median survival was 6.4 months. CONCLUSION: The
      combination of cisplatin, 5-FU and interferon-alpha produces a high response rate
      in advanced squamous cell esophageal carcinoma, but with considerable toxicity. A
      modified combination of the above agents is presently being evaluated at our
      institution.

PMID- 12218270
TI  - Pulpal responses to caries and dental repair.
AB  - The dentine-pulp complex shows a broad spectrum of responses to caries of the
      dental tissues, which represents a summation of injury, defence and repair events
      taking place. The relative importance of these various events will reflect both
      the extent of disease activity and metabolic state of the tissues. This review
      examines the interplay between these events and the opportunities for tissue
      regeneration following caries.

PMID- 12218271
TI  - Causal patterns of dental health in populations. An empirical approach.
AB  - In the present investigation we aimed to analyse causally the pattern of
      determinants leading to the maintenance of functional teeth in adults. Clinical
      and self-reported information was used. The hypothesis was that socio-economic
      conditions operate through psychosocial circumstances that influence lifestyle,
      and are thus related to oral hygiene and levels of remaining teeth. Testing of
      the patterns for adults residing in high- and low-fluoride areas did not reveal
      any principal differences in dental health, therefore further testing was
      combined for both fluoride areas. Further analysis also indicated that testing
      should be performed separately for each gender. Social structure and dental
      health-related lifestyle were important in an overall pattern of maintaining
      functional teeth, but general lifestyle and psychosocial conditions were not
      found to be part of the pattern influencing dental health. Gender-specific
      patterns were revealed. New hypotheses may be suggested for further research with
      regard to studying patterns of dental health in Lithuanian adults.

PMID- 12218272
TI  - Intra- and interexaminer variability and validity of laser fluorescence and
      electrical resistance readings on root surface lesions.
AB  - The purpose of this study was to investigate the validity and reproducibility of
      laser fluorescence and electrical resistance readings on root carious lesions.
      One hundred and three freshly extracted human teeth with various forms of natural
      root caries were investigated by 6 operators using the laser fluorescence device
      DIAGNOdent (DD) and the Electronic Caries Monitor (ECM III). As a reference, a
      caries-free root area of each tooth was also examined. Specimens were classified
      as to colour, surface texture and cavitation depth. Teeth were sectioned through
      the centre of the lesion and prepared for polarising light microscopy.
      Histological depth of the lesions was defined as the distance between the surface
      and zone of translucency. Depths ranged from 0.1 to 3.1 mm. Statistical analysis
      of the interexaminer reproducibility revealed a significant correlation
      (Kendall's W) for DD measurements of 0.85 and 0.76 for ECM readings. Moderate
      correlation between the histological depth and DD (r(s) = 0.45) or ECM scores
      (r(s) = -0.48) could be demonstrated. Electrical resistance readings revealed a
      positive correlation (r(s) = 0.43) with the thickness of the remaining dentine,
      whereas this was negative for laser fluorescence readings (r(s) = -0.43).
      However, scatter plots suggested that most lesions had very low resistance. This
      investigation suggests that laser fluorescence and electrical conductance
      measurements can be obtained reproducibly by different operators and correlate
      moderately with histological lesion depth and remaining thickness of the dentine
      bridge.

PMID- 12218273
TI  - The validity of proximal caries detection using magnifying visual aids.
AB  - The purpose of this study was to determine the validity of proximal caries
      detection supported by a prism loupe and a surgical microscope used by examiners
      having different professional experience. One hundred and sixty extracted
      premolars and molars with varying degrees of proximal caries or sound surfaces
      were embedded in 10 pairs of models with proximal tooth contacts and a simulated
      gingiva mask. The proximal surfaces were visually evaluated by 14 observers (7
      students, 7 dentists) according to a 5-point caries rating scale using a head
      worn prism loupe (x4.5), a surgical microscope (x 14) and without any magnifying
      device (control). The validity of observations was expressed as ROC curves
      calculated for two gold standard thresholds: (a) the presence of caries and (b)
      macroscopic cavitation. Repeated measures analysis of variance was used to
      determine the effects of 'observer group' and 'diagnostic modality'. An influence
      of the observer group could not be demonstrated (p > 0.72), whereas significant
      differences were revealed between the diagnostic modalities (p < 0.002). ROC
      areas of caries detection with magnifying aids were smaller compared to the
      control group. It was concluded that the use of a prism loupe or a surgical
      microscope does not improve the validity of proximal caries detection if the
      operators, irrespective of being dental students or clinical instructors, are
      inexperienced in its utilisation. In general only moderate validity was achieved
      with visual inspection of proximal sites.

PMID- 12218274
TI  - Plaque fluoride concentrations are dependent on plaque calcium concentrations.
AB  - Despite the 1000-fold difference between the fluoride concentrations ([F]) in
      dentifrices and fluoridated drinking water, clinical and epidemiological studies
      have shown that they have similar cariostatic effects. This double-blind,
      crossover study was done to determine whether the [F] in dental plaque is related
      more to the [F] of the dentifrice used or to the plaque concentrations of calcium
      and magnesium. The subjects (n = 13) were adults and residents of a city served
      with fluoridated drinking water. After 1 week of using a fluoridated dentifrice
      (940 ppm) or a placebo dentifrice, whole saliva and plaque were collected 1.0 h
      and approximately 12 h after the last use of the dentifrices. The average
      salivary [F] after brushing with the F dentifrice was higher than after using the
      placebo. The average plaque [F] 1.0 h after brushing with the F dentifrice was
      higher than after using the placebo (p < 0.01), but the difference at 12 h was
      not significant. Plaque [Ca] and [F] were directly related under all experimental
      conditions (p = 0.0001). The relationships between plaque [Mg] and [F] were
      weaker and inconsistent. Based on these findings and reports in the literature it
      is concluded that, for persons whose drinking water is fluoridated, plaque [F]
      throughout much of the day is not significantly increased by the use of a
      fluoridated dentifrice. Instead they are directly related to plaque [Ca]. These
      findings offer at least a partial explanation for why fluoridated dentifrices and
      drinking water have similar cariostatic effects.

PMID- 12218275
TI  - In vitro fluoride uptake by enamel from different amine fluoride concentrations.
AB  - The aim of this in vitro study was to examine whether the concentration of amine
      fluoride solution influences the uptake of fluoride by enamel after topical
      treatment. Four slabs were prepared from each of 31 impacted third molars and
      selected at random so that one slab from each tooth was present in each group.
      One group of slabs served as an untreated control (D). The slabs of the other
      three groups were shaken for 3 min in an amine fluoride solution on 3 successive
      days: group A (1% F), group B (0.5% F) and group C (0.25% F). The amounts of KOH
      soluble fluoride produced with 1 and 0.5% amine fluoride solution did not differ
      significantly and were superior to 0.25% amine fluoride solution. A statistically
      significant increase in structurally bound fluoride was observed in groups A, B
      and C compared with control group D. The difference in the amounts of
      structurally bound fluoride was significant only between 1 and 0.25% F
      concentrations. These data suggest that the fluoride content in an amine fluoride
      solution (1%) can be decreased by half without reducing its ability to form
      alkali-soluble or structurally bound fluoride. The results of this study are
      consistent with those of previous clinical studies.

PMID- 12218277
TI  - Remineralization of advanced root dentin lesions in vitro.
AB  - The possibility for remineralization of advanced root dentin lesions was
      investigated in vitro. Lesions were produced in acidic buffer solution with 0.1
      and 0.5 ppm fluoride, for 3 and 5 weeks, respectively, using a single-section
      model. Next, the sections were immersed in a remineralization solution containing
      0.1 ppm F (as NaF) for 20 weeks. Microradiographs were made after each 4-week
      period. The lesions were around 500 micro m deep, with mineral loss values
      between 11,000 and 18000 vol%.microm. After 20 weeks of remineralization, the
      absolute amounts of deposited mineral ranged from 7500 to 10000 vol%. micro m,
      corresponding to a repair between 50 and 85%. Lesion depth was, on average,
      reduced by 199 micro m. This was not significantly different (at p < 0.05)
      between the four experimental groups. This study showed that remineralization of
      advanced dentinal lesions is possible in spite of the virtual absence of mineral
      in the lesion body after demineralization. The surface layer of the lesion was
      the preferred site for mineral deposition until mineral content values reached
      those of sound dentine. The mineral content in the lesion body increased with
      time, at a rate reflecting the initial severity of the lesion. We conclude that a
      remineralized surface layer does not inhibit transport of mineral ions to the
      body and that the remineralization in the lesion body reflected the number of
      sites for crystal growth.

PMID- 12218276
TI  - Remineralisation of enamel lesions with daily applications of a high
      concentration fluoride gel and a fluoridated toothpaste: an in situ study.
AB  - The inhibition of enamel demineralisation and the enhancement of remineralisation
      are positively but not linearly related to the concentration of fluoride,
      especially when high fluoride concentrations are used. The aim of this in situ
      experiment was to determine the maximum amount of enamel remineralisation that
      can be achieved with daily applications of very high concentrations of fluoride.
      For this purpose we compared the efficacy of a daily application of fluoridated
      topical gel (12500 ppm F, partly as NaF, Olafluor and Dectafluor, pH 4.5) in
      combination with a fluoridated toothpaste (1450 ppm F as NaF), with fluoridated
      toothpaste alone. Participants (n = 26, with partial dentures) were fitted with a
      demineralised enamel specimen (mean mineral loss of 1674 vol%.micro m) and were
      instructed to use one of the two fluoride treatments. After 4 weeks of treatment,
      the specimens were retrieved, a section was cut and analysed with
      microradiography. The remainder of each of the specimens was used for analysis of
      the 'loosely bound' and 'bound' fluoride. Fluoride was measured with gas-liquid
      chromatography. After 4 weeks in the mouth, the original lesion was reduced in
      size by 54% in the toothpaste + gel group (n = 14) and by 44% in the toothpaste
      only group (n = 12), but the difference between the groups was not statistically
      significant. The mineral content profiles showed remineralisation of the lesions
      throughout the depth of the lesion. The enhancement of remineralisation by the
      high amounts of fluoride was most pronounced in the surface layer. For both the
      'loosely bound' and 'bound' fluoride, a statistically significant increase in
      fluoride concentration could be found in the toothpaste + gel group. In the 4
      week in situ period the use of high amounts of fluoride resulted in a maximum
      remineralisation rate. This is illustrated by an increase in remineralisation and
      higher fluoride concentrations in the toothpaste + gel group compared to the
      toothpaste-only group.

PMID- 12218278
TI  - Relationship between sports drinks and dental erosion in 304 university athletes
      in Columbus, Ohio, USA.
AB  - Acidic soft drinks, including sports drinks, have been implicated in dental
      erosion with limited supporting data in scarce erosion studies worldwide. The
      purpose of this study was to determine the prevalence of dental erosion in a
      sample of athletes at a large Midwestern state university in the USA, and to
      evaluate whether regular consumption of sports drinks was associated with dental
      erosion. A cross-sectional, observational study was done using a convenience
      sample of 304 athletes, selected irrespective of sports drinks usage. The Lussi
      Index was used in a blinded clinical examination to grade the frequency and
      severity of erosion of all tooth surfaces excluding third molars and incisal
      surfaces of anterior teeth. A self-administered questionnaire was used to gather
      details on sports drink usage, lifestyle, health problems, dietary and oral
      health habits. Intraoral color slides were taken of all teeth with erosion.
      Sports drinks usage was found in 91.8% athletes and the total prevalence of
      erosion was 36.5%. Nonparametric tests and stepwise regression analysis using
      history variables showed no association between dental erosion and the use of
      sports drinks, quantity and frequency of consumption, years of usage and nonsport
      usage of sports drinks. The most significant predictor of erosion was found to be
      not belonging to the African race (p < 0.0001). The results of this study reveal
      no relationship between consumption of sports drinks and dental erosion.

PMID- 12218280
TI  - A randomised controlled trial of the efficacy of supervised toothbrushing in high
      caries-risk children.
AB  - Scottish children have one of the highest levels of caries experience in Europe.
      Only 33% of 5-year-old children in Dundee who developed caries in their first
      permanent molars by 7 brushed their teeth twice a day. High-caries-risk children
      should benefit if they brush more often with fluoridated toothpaste. The aim of
      this clinical trial was to determine the reduction in 2-year caries increment
      that can be achieved by daily supervised toothbrushing on school-days with a
      toothpaste containing 1,000 ppm fluoride (as sodium monofluorophosphate) and
      0.13% calcium glycerophosphate, combined with recommended daily home use,
      compared to a control group involving no intervention other than 6-monthly
      clinical examinations. Five hundred and thirty-four children, mean age 5.3, in
      schools in deprived areas of Tayside were recruited. Each school had two parallel
      classes, one randomly selected to be the brushing class and the other, the
      control. Local mothers were trained as toothbrushing supervisors. Children
      brushed on school-days and received home supplies. A single examiner undertook 6
      monthly examinations recording plaque, caries (D(1) level), and used FOTI to
      supplement the visual caries examination. For children in the brushing classes,
      the 2-year mean caries increment on first permanent molars was 0.81 at D(1) and
      0.21 at D(3) compared to 1.19 and 0.48 for children in the control classes
      (significant reductions of 32% at D(1) and 56% at D(3)). In conclusion, high
      caries-risk children have been shown to have significantly less caries after
      participating in a supervised toothbrushing programme with a fluoridated
      toothpaste.

PMID- 12218279
TI  - Lack of effect of chlorhexidine varnish on Streptococcus mutans transmission and
      caries in mothers and children.
AB  - In a randomized clinical trial, we evaluated the effect of a 10% chlorhexidine
      varnish (Chlorzoin) on the mother-child transmission of Streptococcus mutans and
      on subsequent caries experience. Chlorhexidine (n = 38) or a placebo varnish (n =
      37) was applied to the dentitions of 75 mothers at a time when their first babies
      were about 6 months old (approximate time of first tooth emergence). Three more
      applications at weekly intervals and subsequent applications at 6-month intervals
      followed the initial application. The mother-child pairs were followed up until
      the child's fourth birthday. Maternal salivary S. mutans levels in the treatment
      group remained significantly lower (p < 0.05) compared to the control group up to
      12 months after the initial application. However, this intervention did not
      significantly alter the S. mutans colonization in children or the caries
      increment in either the mother or the child.

PMID- 12218281
TI  - Comparative histologic effects of daily topical application of creams containing
      all-trans-retinoic acid or all-trans-retinoyl beta-glucuronide on pig skin.
AB  - The efficacy of all-trans-retinoic acid (tRA) and all-trans-retinoyl beta
      glucuronide (RAG), a water-soluble metabolite of vitamin A, in the topical
      treatment of acne is comparable. However, whereas 3.3 mM tRA shows side effects,
      3.3 mM RAG does not. To assess the relative toxic and histologic effects (dermal
      and epidermal changes) of long-term (24-week) daily applications of tRA and RAG
      on the skin, separate skin patches were measured and marked dorsally on the skin
      of six 21-day-old, castrated male pigs. Each skin patch area was treated daily
      with a cream formulation containing either 3.3 mM RAG, 16.5 mM RAG, 33 mM RAG,
      3.3 mM tRA, 16.5 mM tRA or blank cream. To serve as controls, one patch received
      no treatment, one patch received blank cream only and for 5.3 weeks one 'washed'
      patch was given daily application of 33 mM RAG with routine cleansing using a
      mild soap typical of skin care. The amount of cream used per square centimeter
      remained the same during the course of the study. Biopsy tissue was collected at 
      1, 0, 2, 4, 8, 12 and 24 weeks from 7 test patches. The 'washed' patch was
      biopsied once at the 5.3-week mark. Topically applied RAG cream (3.3 mM) resulted
      in significantly lower histologic scores when compared with scores from tissue
      treated with an equimolar concentration of tRA. The highest concentration of RAG
      tested (33.3 mM) resulted in a response comparable to that observed in the lowest
      tRA (3.3 mM) treated patch area. Daily cleansing of the test area receiving 33.3
      mM RAG completely eliminated any clinical signs or negative histologic changes.
      In conclusion, long-term topical tRA treatment in young pigs, as in humans,
      showed dose-dependent adverse effects on the skin, whereas RAG treatment had
      significantly lower histologic changes and less irritation and/or inflammation.

PMID- 12218282
TI  - Screening topical antipruritics: a histamine-induced itch human model.
AB  - Itch is a subjective symptom; its magnitude (intensity) may be only estimated by
      the reports of patients or volunteers. We utilized a comparative screening method
      to identify and quantify the efficacy of topical antipruritics with a histamine
      induced itch human model. Ten individuals responsive to histamine-induced itch
      sensation were enrolled. Both forearms served as test sites. Each test site was
      treated randomly either by histamine injection only or pretreated with a coded
      candidate formula for 30 min and then a histamine injection. Itch was
      experimentally induced in each test site by the intracutaneous injection of 100
      microg histamine dihydrochloride dissolved in 1 ml normal saline. Itch magnitude
      was measured each minute after histamine injection for 20 min with a magnitude
      visual analogue scale. Itch duration was also recorded. Formulation D
      significantly (p < 0.05) decreased itch magnitude (within a 20-min test period),
      from 2.6 +/- 2.1 cm (mean +/- SD) to 2.2 +/- 2.1 cm (mean +/- SD) when compared
      to its vehicle control; it also significantly (p < 0.05) shortened itch duration
      (15.0 +/- 7.4 min; mean +/- SD) in comparison with its vehicle control (20.3 +/-
      7.0 min; mean +/- SD). Of all the formulations tested, formulation D was the most
      effective antipruritic in decreasing histamine-induced itch. This method may act
      as a simple and robust screening procedure when evaluating potential
      antipruritics and allow a comparison among products. Until validated with disease
      induced itch, e.g., atopic dermatitis, the model should be considered screening
      in nature.

PMID- 12218283
TI  - Suppression of spontaneous scratching in hairless rats by sedatives but not by
      antipruritics.
AB  - Experimental scratching in animals has hitherto been provoked by substances
      injected into the skin or central nervous system. We aimed to investigate if
      spontaneous scratching in the rat can be reduced by sedatives and antipruritics,
      and to assess if spontaneous scratching is elicited from the skin or the central
      nervous system. It may also be a complex behaviour related to the rat species,
      different from clinical itch. Eight male hairless rats were studied for 6 weeks.
      The animals were recorded on videotape in the middle of the day and at night, and
      the scratching activity was counted. The following substances were tested
      sequentially: midazolam, mepyramine, a eutectic mixture of lignocaine and
      prilocaine (EMLA, betamethasone dipropionate and a vehicle. On days 1-3 of each
      sequence, the test material was applied to a 42-cm(2) area on the rostral part of
      the back. Subsequent treatment of the whole body was made on day 4. Midazolam was
      injected intraperitoneally from day 1 to day 4. After 4 days of treatment, there
      was a wash-out phase of 3 days until the next sequence. We found a positive
      correlation between minutes awake and number of scratch episodes. Spontaneous
      scratching was lower after mepyramine on day 4 (p = 0.046) and after midazolam
      injections on days 1-3 (p = 0.009) and day 4 (p = 0.003). The local anaesthetic,
      EMLA, did not significantly influence spontaneous scratching. In conclusion, only
      the drugs with sedative properties suppressed spontaneous scratching, which is
      probably a cerebral phenomenon or otherwise explained general behaviour, rather
      than a reaction to skin stimuli. Thus, for testing of topically applied
      antipruritics, spontaneous scratching cannot be used as an animal model.
      Furthermore, evaluation of provocative scratching should eliminate/exclude
      spontaneous scratching.

PMID- 12218284
TI  - Evaluation of barrier creams against sulphur mustard. I. In vitro studies using
      human skin.
AB  - The purpose of this study was to assess the effectiveness of a range of passive
      and reactive barrier cream formulations against the chemical warfare agent
      sulphur mustard (SM) using an in vitro diffusion cell system containing human
      skin. In general, proprietary formulations were relatively effective under
      occluded conditions, but ineffective under unoccluded conditions. For example, SM
      skin absorption rates through occluded control and Stokoderm pre-treated skin
      were 538 +/- 193 and 200 +/- 51 microg x cm(-2) x h(-1), respectively (p < 0.05).
      Under unoccluded conditions, control and Stokoderm pre-treated skin absorption
      rates were 4.41 +/- 1.90 and 36.84 +/- 15.19 microg x cm(-2) x h(-1) (p < 0.05).
      Novel (perfluorinated) barrier creams were generally more effective under
      unoccluded conditions; pre-treatment with one formulation led to an 18-fold
      reduction in skin absorption rate and reduced the total amount of SM penetrated
      by 95% of the applied dose. Several proprietary formulations also had adverse
      effects on the effectiveness of the skin decontaminant fuller's earth. The rate
      (Jss) and total amount (percentage of dose) of SM absorbed through the skin were
      deemed to be independent parameters of barrier cream performance. These data
      indicate that (1) perceived conditions of use, (2) compatibility with existing
      protective equipment and (3) the rate and extent of SM skin absorption must all
      be taken into account when evaluating barrier creams in vitro.

PMID- 12218285
TI  - Effect of glycolic acid on UVB-induced skin damage and inflammation in guinea
      pigs.
AB  - OBJECTIVES: Recently the use of glycolic-acid-containing cosmetics has received
      increased public interest in their supposed ability to reduce wrinkles,
      roughness, age spots and other skin damage. However, the safety of such products
      when used excessively or chronically, especially by photosensitive people, is
      being questioned. The purpose of this study was to examine the effects of
      glycolic acid alone or in combination with UVB on skin damage and inflammatory
      response. METHOD: Guinea pigs were treated with glycolic acid (from 1 to 7
      mg/cm(2)) alone or in combination with UVB (0.4 or 3 J/cm(2)) for 14 days. Skin
      damage was evaluated by scoring the skin irritation value by the method of Draize
      and by histopathological observations. Cyclooxygenase 2 (COX-2) expression and
      prostaglandin E(2) (PGE(2)) production were also assessed. RESULTS: Glycolic acid
      caused an increase in the level of skin damage in a dose- and time-dependent
      manner. Lower doses (1 and 3 mg/cm(2)) of glycolic acid mostly caused erythema
      and eschar, and these consequently formed scales, whereas higher doses (5 and 7
      mg/cm(2)) of glycolic acid caused redness, edema and necrotic ulceration.
      Glycolic acid also increased the thickness of the epidermal layer, reduced the
      organization of the stratum corneum and eventually destroyed some parts of the
      epidermal layer at 7 mg/cm(2). UVB (0.4 and 3 J/cm(2)) caused redness and edema
      as well as reduced the integrity of the stratum corneum. Glycolic acid enhanced
      the UVB-induced skin damage. The magnitude of the damage caused by combined UVB
      and glycolic acid treatment was much greater than that caused by glycolic acid or
      UVB alone. Moreover, partial destruction of the epidermal layer was observed in
      skin treated with 3 J/cm(2) UVB and 3 mg/cm(2) glycolic acid. However, glycolic
      acid did not change the basal and UVB-induced PGE(2) production and COX-2 protein
      expression. CONCLUSION: These results show that glycolic acid causes skin damage
      in a dose- and time-dependent manner and that it enhances UVB-induced skin damage
      without accompanying PGE(2) production or COX-2 protein expression. Therefore,
      caution should be exercised by those using glycolic acid on a chronic basis or
      excessively. Moreover, those with photosensitive skins and those more exposed to
      the sun should be particularly careful.

PMID- 12218286
TI  - Calcipotriol plus short-contact dithranol: a novel topical combination therapy
      for chronic plaque psoriasis.
AB  - The purpose of this double-blind randomised parallel-group study was to compare
      the efficacy and safety of short-contact treatment with dithranol ointment (2%)
      with its combination with calcipotriol ointment (50 microg/g) in 2 groups of in
      patients with chronic plaque psoriasis. The patients of the first group (n = 23)
      topically applied dithranol once daily for 30 min and the vehicle of calcipotriol
      twice daily. The patients of the second group (n = 23) used a single topical
      application of dithranol for 30 min daily and additionally applied calcipotriol
      twice daily. The extent and the severity of psoriasis were assessed by means of
      psoriasis area and severity index score (PASI score) before the onset of the 6
      week therapy and weekly thereafter. The difference between the two groups with
      regard to the mean PASI score became statistically significant already after the
      first week of treatment and remained so until the end of the trial. No
      significant differences were observed between the two groups with respect to the
      cutaneous adverse events. These findings indicate that the addition of
      calcipotriol ointment to short-contact dithranol markedly augments the
      therapeutic efficacy of the latter in chronic plaque psoriasis and impressively
      accelerates the response of psoriatic plaques to this well-tolerated regimen.

PMID- 12218287
TI  - A simple technique for high-throughput screening of drugs that modulate normal
      and psoriasis-like differentiation in cultured human keratinocytes.
AB  - Established treatments for psoriasis act ei-ther on hyperproliferation,
      inflammation, aberrant epidermal differentiation or a combination of these
      aspects of the disease. Potential new drugs for treatment of psoriasis or other
      disorders with abnormalities in epidermal differentiation can be identified by
      high-throughput screening of large compound libraries using surrogate markers for
      the disease. Here we describe a screening model to detect pharmacologically
      active drugs in two keratinocyte-based, 96-well culture models that use
      expression of cytokeratin 10 (CK10) and skin-derived antileucoprotease
      (SKALP)/elafin as markers for normal and psoriatic differentiation, respectively,
      and allow multiple parameters to be determined from a single well. In this model
      we tested a number of compounds in a pharmacological range from 10(-7) to 10(-5)
      M, including known antipsoriatic drugs, and experimental drugs that are
      potentially useful in the treatment of psoriasis. All-trans-retinoic acid,
      dithranol and the p38 mitogen-activated protein (MAP) kinase inhibitor SB220025
      displayed a strong inhibitory effect on SKALP expression while cyclosporin A,
      dexamethasone, the vitamin D(3) derivative calcipotriol and the p38 MAP kinase
      inhibitor SB203580 showed only moderate inhibition. Methotrexate and
      dimethylfumarate did not affect the expression of SKALP. With respect to CK10
      expression, all-trans-retinoic acid, calcipotriol, SB203580 and SB220025
      exhibited strong inhibition while dithranol showed only moderate suppression of
      this normal differentiation marker. Expression levels of CK10 were not
      significantly affected by dexamethasone, methotrexate, cyclosporin A or
      dimethylfumarate. This model system parallels most, but not all, findings on the
      in vitro effect of known antipsoriatic drugs on keratinocytes. In addition, the
      model identifies p38 MAP kinase inhibitors as potent suppressors of
      differentiation-associated gene expression. Although further delineation and
      validation of this model is required, we conclude that the system is amenable to
      down-scaling and application as a high-throughput screen for differentiation
      modifying compounds.

PMID- 12218288
TI  - The response of normal human skin to single and repeated applications of
      dithranol cream: an immunohistochemical assessment.
AB  - The irritative response of uninvolved skin is a serious limitation of dithranol
      therapy in psoriasis. A characterisation in cell biological terms may be helpful
      in finding an effective counteraction to this well-known irritation. Therefore,
      we studied the effect of single and repeated applications of dithranol on normal
      human skin. Besides a clinical evaluation, we studied aspects of epidermal
      proliferation, differentiation and inflammation. On day 2, after single dithranol
      challenge, we observed an induction of both the cornified envelope precursor
      protein involucrin and the cross-linking enzyme transglutaminase I. Subsequently,
      epidermal hyperproliferation was observed with a maximum on day 8. The epidermal
      response to dithranol appears to be a reinforcement of the barrier function.
      Remarkably, however, filaggrin was found to be decreased. Profilaggrin breakdown
      might be an attempt to compensate for xerosis of uninvolved skin that accompanies
      dithranol therapy. T lymphocytes and to a lesser extent polymorphonucleocytes
      were found to be significantly increased. The reduction of Langerhans cells
      suggests a dose-dependent toxic effect of dithranol or one of its metabolites on
      Langerhans cells. The dynamics in the induction of changes after repeated
      challenge are comparable with those after single challenge. However, the
      induction of hyperproliferation following repeated application appeared to
      continue between day 8 and 12. Based on the dynamics of dithranol-induced
      irritation, it may be of interest to study the efficacy of intermittent dithranol
      treatment. Our results indicate that an optimal timing for biopsies in future
      dithranol irritation studies lies between 4 and 8 days after the first dithranol
      challenge.

PMID- 12218289
TI  - 12th International conference on cytochrome p450. Biochemistry, biophysics and
      molecular biology.

PMID- 12218290
TI  - From the clinic to genome: a way to new drugs and therapy? Workshop of the
      Bundesverband der Pharmazeutischen Industrie eV (BPI), Berlin, Germany.

PMID- 12218291
TI  - Isolation and characterization of thomsen-friedenreich-specific antibodies from
      human serum.
AB  - The Thomsen-Friedenreich (TF) disaccharide, galactose (Gal)beta1-3GalNAcalpha-,
      is a blood group-related oncofetal antigen with remarkable tumor specificity.
      Postpartum, carbohydrate structures on the cell walls of the gastrointestinal
      flora evoke natural antibodies of presumed TF specificity. These antibodies may
      provide an early barrier against TF-carrying tumor cells. Their possible role,
      however, has been difficult to assess, since so far only a multivalent
      immunosorbent, asialoglycophorin (aGP), has been employed for their preparation,
      and therefore their fine specificities have been only insufficiently defined. We
      have used a novel immunosorbent consisting of synthetic TFalpha disaccharides
      (Galbeta1-3GalNAcalpha-) coupled to polyacrylamide (PAA), which itself was
      covalently bound to cross-linked sepharose. For specificity analyses, aGP and a
      panel of PAA-conjugated mono- and oligosaccharides were employed. Binding to the
      PAA moiety was excluded. The affinity-purified anti-TFalpha antibodies were of
      the IgM (> or =0.5 mg/100 ml of serum) and IgG (approximately 0.05 mg/100 ml of
      serum) classes. They did partially cross-react with TFbeta, although we detected
      a second group of anti-TFbeta antibodies (both IgM and IgG) which did not cross
      react with TFalpha. The affinity-purified TFalpha antibodies showed only marginal
      cross-reactivity with the related antigens lactose, Gal, Tn or the Forssman
      antigen. Besides TF-specific antibodies, we found antibodies to the carbohydrate
      antigens Tn, Forssman and beta-D-Gal as well as to noncarbohydrate epitopes of
      glycophorin in human serum.

PMID- 12218292
TI  - Production of macrophage migration inhibitory factor by human and murine
      neuroblastoma.
AB  - Tumor cells avoid immune recognition by subverting the ability of the immune
      system to mount an inflammatory response that generates cytotoxic effector cells.
      This can be achieved through cytokine production by the tumor itself. Our
      objective was to determine the cytokine profile of neuroblastoma (NB) lesions in
      tumor vaccine models. We found that the murine NB cell line, Neuro2a, secretes
      macrophage migration inhibitory factor, MIF, a multifunctional cytokine with the
      potential to block effective immune responses to a tumor. Patient-derived NB cell
      lines were also found to produce MIF. MIF production by NB was documented at the
      level of RNA by RNAse protection, soluble cytokine production by ELISA, and in a
      macrophage migration assay. Our studies also confirmed reports of IL-6 production
      by human NB cell lines. NB culture-derived MIF was also shown to activate tumor
      cell migration. This supports the hypothesis that MIF is a tumor-derived cytokine
      that may play a role in NB aggressiveness and evasion of immune recognition.

PMID- 12218293
TI  - Local expression of insulin-like growth factor-I affects angiogenesis in
      colorectal cancer.
AB  - Insulin-like growth factor-I (IGF-I) has potent mitogenic and anti-apoptotic
      effects that give it a critical role in the regulation of rapidly renewing
      epithelial cell populations such as those found in the colon. Recent evidence has
      implicated circulating IGF-I levels as an important determinant of colorectal
      cancer risk, but the role, if any, of its autocrine/paracrine expression remains
      unexplored. Therefore, we investigated the local expression of IGF-I and IGF-I
      type I receptor (IGF-IR) in 50 paired normal colon and carcinoma samples. IGF-IR
      mRNA was present in all samples, whereas IGF-I mRNA was detected in only 30
      normal (60%) and 27 tumour (54%) biopsies. Samples that did not express IGF-I
      mRNA had no IGF-I peptide detectable by immunocytochemistry. The absence of local
      IGF-1 expression was associated with significantly reduced mRNA levels specifying
      the proliferating cell nuclear antigen and c-myc, as well as Cox-2, and vascular
      endothelial growth factor - gene products that regulate angiogenesis. The
      biological relevance of this finding is suggested by the significant association
      between local IGF-I mRNA levels and microvessel density in the colorectal
      cancers.

PMID- 12218294
TI  - Expression profiling of mammary carcinoma cell lines: correlation of in vitro
      invasiveness with expression of CD24.
AB  - Invasiveness and the capacity of tumor cells to form distant metastases are
      important cellular characteristics associated with a poor prognosis in breast
      cancer patients. In an approach to find genes that are potentially involved in
      these processes, RNA species showing different abundance in RNA pools from 12
      invasive and 13 noninvasive mammary carcinoma-derived cell lines have been
      identified by hybridization to cDNA microarrays. CD24, keratin 19, keratin 8, GOB
      4 and ezrin-radixin-moesin-binding phosphoprotein 50 were found to be
      preferentially expressed by noninvasive cells whereas vimentin was confirmed as a
      characteristic of invasive cells. Only differences in expression higher than 3
      fold evident in three independent hybridization experiments were considered
      significant. For all cell lines, expression of mRNA coding for the adhesion
      molecule CD24, previously suggested to play an important role during tumor
      progression to more invasive phenotypes, has been quantified by real-time RT-PCR.
      Flow-cytometric analyses confirmed that CD24 mRNA reflects the amount of cell
      surface CD24 (Spearman R = 0.88, p = 10(-6)). CD24 mRNA was found to be absent or
      weakly expressed in 9/12 (75%) invasive cell lines compared to 3/13 (23%)
      noninvasive cell lines. The correlation between CD24 expression and invasiveness
      was calculated to be highly significant with chi2 = 6.74 and p = 0.0094. Future
      analyses of primary breast carcinomas are warranted to define the role of CD24 in
      future diagnostic and therapeutic approaches.

PMID- 12218295
TI  - Serum levels of soluble transferrin receptor correlate with severity of disease
      but not with iron stores in patients with malignant lymphomas.
AB  - Soluble transferrin receptor levels in serum (s-sTfR) may be useful in
      differentiating between iron deficiency anemia and anemia of chronic disease.
      However, there is both theoretical and clinical evidence for elevated s-sTfR
      levels in patients with various hematological malignancies. In the present study,
      routine bone marrow aspirations were performed in 82 patients with malignant
      lymphomas (63 with non-Hodgkin's lymphoma and 19 with Hodgkin's disease). Smears
      were stained for evaluation of iron stores and graded. Patients were also given a
      disease score based on bone marrow morphology, erythrocyte sedimentation rate and
      LDH. s-sTfR levels correlated better with disease score [partial Spearman rank
      correlation coefficient (r(s)) controlled for iron stores was 0.51 (95%
      confidence interval 0.39-0.65); p < 0.001] than with iron stores [partial r(s)
      controlled for disease score was -0.25 (95% confidence interval -0.44 to -0.03);
      p = 0.027]. This study showed elevated s-sTfR levels in patients with malignant
      lymphomas without any signs of iron deficiency anemia. The diagnosis of iron
      deficiency anemia should not be established upon the basis of s-sTfR alone in
      this group of patients.

PMID- 12218296
TI  - The CA 125 gene: a newly discovered extension of the glycosylated N-terminal
      domain doubles the size of this extracellular superstructure.
AB  - CA 125 is a well-established marker for patients diagnosed with ovarian
      carcinoma. It is clearly elaborated in serous cystadenocarcinomas and less likely
      to be expressed in mucinous tumors. It has been 20 years since CA 125 was first
      recognized and it is only in recent years (the past 2) that some progress has
      been made toward cloning the gene, providing the basis for an understanding of
      the functional role of this molecule in embryonic development and neoplastic
      transformation. It is now clear that CA 125 is a large glycoprotein which is
      anchored to the epithelium by a transmembrane domain and is released into the
      extracellular space by enzymatic cleavage. Here, we describe a further major
      extension to the glycosylated extracellular amino terminal domain of this
      molecule. These additional data in association with our previous understanding of
      this molecule will provide the basis for our ability to understand the
      physiologic function of this molecule in biologic development and pathologic
      transformation.

PMID- 12218297
TI  - Significance of urokinase-type plasminogen activator and plasminogen activator
      inhibitor-1 (PAI-1) expression in human colorectal carcinomas.
AB  - Despite the advances in the medical care of colorectal carcinoma patients, the
      prognosis has improved only marginally over recent decades. Thus, additional
      prognostic indicators would be of great clinical value to select patients for
      adjuvant therapy. In the present study, the antigen levels of urokinase-type
      plasminogen activator (uPA) and its inhibitor PAI-1, and their
      immunohistochemical staining were compared in paired colorectal tumor (n = 64)
      and background colon tissue of the same patients with clinical and pathological
      staging. The antigen levels, measured with an ELISA method, were found to be
      significantly higher in cancer tissue (mean 1.92 ng/mg protein for uPA and 7.08
      for PAI-1) than in corresponding normal mucosa (0.29 ng/mg protein for uPA and
      1.11 ng/mg protein for PAI-1). There was a positive correlation between uPA and
      PAI-1 antigen levels and clinicopathological parameters such as grade (p < 0.001
      and p = 0.01, respectively), while for Dukes' stage, only PAI-1 correlated
      positively (p = 0.018). Nodal status correlated positively with uPA but not with
      PAI-1 antigen levels. Immunohistochemical localization of both antigens was
      observed mainly in cancer cells and much less in stromal cells. Staining
      intensity increased from adenoma to adenocarcinoma. The degree of staining was
      associated with grade, Dukes' stage and nodal status for uPA (p < 0.001, p =
      0.002, p < 0.001, respectively) and only with grade for PAI-1 (p = 0.007).

PMID- 12218298
TI  - Differential expression and activity status of MMP-1, MMP-2 and MMP-9 in tumor
      and stromal cells of squamous cell carcinomas of the lung.
AB  - Matrix metalloproteinases (MMPs) play a key role in cancer progression.
      Interstitial collagenase (MMP-1) and type IV collagenases (MMP-2, MMP-9) are
      involved in the initial breakdown of collagen and basement membrane components
      during tumor growth and invasion. Besides tumor cells, fibroblasts are especially
      involved in MMP production. The aim of this study was to quantify MMP-1, MMP-2
      and MMP-9 within tumor cells and tumor-surrounding fibroblasts compared to normal
      lung epithelial cells to gain an insight into the function of these MMPs in
      squamous cell carcinomas of the lung. The expression and activity of MMP-1, MMP-2
      and MMP-9 were analyzed in 30 squamous cell carcinomas and in normal lung tissue
      from the same patients by immunohistology and gelatin zymography. The majority of
      tumor cells were positive for MMP-1 (mean +/- SD: 67.3 +/- 26.7%) and MMP-9 (64.7
      +/- 22.8%), whereas a significantly lower percentage of normal bronchoepithelial
      cells (47.3 +/- 25.4 and 40.3 +/- 24.2%, respectively; p < 0.01) and fibroblasts
      located in the tumor-surrounding tissue (39.7 +/- 14.3 and 38.1 +/- 24.1%,
      respectively; p < 0.01) expressed these MMPs. Only a few tumor cells showed any
      immunoreactivity for MMP-2 (4.4 +/- 6.7%), whereas a higher percentage of
      fibroblasts tested positive for this enzyme (8.6 +/- 13.1%; p < 0.01). Using
      gelatin zymography, we could demonstrate that MMP-2 is activated in the tumor
      only, not in normal lung tissue. The coordinated expression of MMP-1, MMP-2 and
      MMP-9 in tumor cells and/or their induction in tumor-surrounding fibroblasts and
      further activation in the tumor tissue may be involved in the high invasive and
      metastatic potential of squamous cell carcinomas of the lung. Comparing the
      results from immunohistology and zymography can give indications for distribution
      and activity of proteinases, especially certain MMPs such as MMP-2.

PMID- 12218299
TI  - Expanded human tissue kallikrein family--a novel panel of cancer biomarkers.
AB  - The full characterization of the human kallikrein gene locus has allowed
      identification of all members of this gene family on chromosome 19q13.4 and the
      establishment of common structural criteria, at both the mRNA and protein level.
      The human kallikrein gene family now consists of 15 members; their mRNA and
      protein structure, tissue expression and hormonal regulation patterns have been
      delineated. In addition to prostate-specific antigen (PSA, hK3), which is an
      established tumor marker for prostate cancer diagnosis and follow-up, and human
      glandular kallikrein (hK2), an emerging prostate cancer biomarker, accumulating
      evidence indicates that many other members of the human kallikrein gene family
      are also implicated in endocrine-related malignancies. Many kallikreins are
      differentially regulated in breast, prostate, ovarian and testicular cancers. In
      addition, preliminary reports indicate that three newly identified kallikreins
      (hK6, hK10 and hK11) are serum biomarkers for diagnosis and monitoring of ovarian
      and prostate cancer. The mechanism by which kallikreins might be involved in the
      pathogenesis and/or progression of cancer is not as yet fully understood.
      Preliminary reports indicate a possible role of kallikreins in controlling vital
      processes, like apoptosis, angiogenesis and tumor metastasis by cleavage of
      critical substrates such as growth factors, hormones or extracellular matrix. In
      this review, we present data on the differential expression of kallikreins in
      cancer at both the mRNA and protein levels, and propose future directions of
      research towards our understanding of the involvement of kallikreins in cancer
      and their possible diagnostic, prognostic and therapeutic applications.

PMID- 12218300
TI  - High-volume hemofiltration in sepsis. Theoretical basis and practical
      application.

PMID- 12218301
TI  - Stenosis of the glomerulotubular neck.

PMID- 12218302
TI  - Future directions in the treatment of IgA nephropathy.
AB  - IgA nephropathy (IgAN) is the most common primary glomerulonephritis yet its
      etiology remains uncertain. Recent data suggest a structural aberration of the
      IgA molecule in IgAN that may exert pathophysiologic effects on target cells,
      reduce clearance of IgA-immune complexes (IC), or favor mesangial IC trapping.
      Mesangial reactivity to immune complexes triggers off the release of cytokines
      and the alteration of prostaglandin and thromboxane A(2) production promoting
      mesangial cell proliferation. Angiotensin II-induced mesangial cells contraction
      with efferent arteriolar vasodilatation initiates glomerular injury and
      eventually lead to glomerulosclerosis following increased local production of
      transforming growth factor-beta (TGF-beta) and platelet-derived growth factor
      (PDGF). This paper highlights the potential therapeutic strategies in the future.
      These strategies include: (i) decreasing the synthesis of IgA-IC; (ii) limiting
      the mesangial uptake of IgA-IC; (iii) antagonizing the effect of PDGF and TGF
      beta to reduce mesangial proliferation and glomerulosclerosis; and (iv) reducing
      the noxious glomerular injury due to infiltrating neutrophils. The effective
      treatment of IgAN requires a better clarification of the pathogenesis of the
      nephropathy. Future therapeutic attempts to slow down the renal deterioration
      should target at prevention of mesangial IgA deposition and the amelioration of
      inflammatory injury induced by infiltrating neutrophils and the released
      cytokines.

PMID- 12218303
TI  - Quantitative analysis of glomerular type IV collagen alpha3-5 chain expression in
      children with thin basement membrane disease.
AB  - Thin basement membrane disease (TBMD) and Alport syndrome, two forms of childhood
      nephritis, have generally been considered to be hereditary diseases. In Alport
      syndrome, several reports have demonstrated pathogenic mutations of the genes
      encoding type IV collagen alpha3, 4 and/or 5 chain [alpha3, 4 and/or 5(IV)].
      Previous immunohistochemical studies indicated that these antigens were absent
      from the glomerular basement membrane (GBM) in Alport syndrome, whilst a normal
      labeling pattern was maintained in TBMD. In order to understand the role of the
      alpha3, 4 and/or 5(IV) antigens in TBMD, we used confocal laser scanning
      microscopy (CLSM) to examine cryosections of renal biopsies from 12 children with
      TBMD and 11 control children with IgA nephropathy (IgAN) without proteinuria. All
      tissue sections were stained with a mixture of FITC-conjugated rat monoclonal
      antibodies directed against human alpha3(IV), alpha4(IV) or alpha5(IV) and a
      Texas red-conjugated rat monoclonal antibody raised against human alpha2(IV).
      CLSM was performed and quantitative analysis of the ratio of the staining signal
      for alpha3(IV), alpha4(IV) or alpha5(IV) to alpha2(IV) [alpha3(IV), alpha4(IV) or
      alpha5(IV)/alpha2(IV)] along the GBM was determined. The average number of pixels
      for alpha3(IV), alpha4(IV) or alpha5(IV)/alpha2(IV) was 3.52 +/- 1.49, 3.54 +/-
      1.25 and 1.09 +/- 0.49 in TBMD and 3.62 +/- 1.46, 3.99 +/- 1.53 and 1.77 +/- 0.47
      in control subjects, respectively. Statistical analysis indicated that
      alpha5(IV)/alpha2(IV) ratio was significantly lower (p < 0.01) in children with
      TBMD compared to controls. These findings raise the possibility that TBMD might
      be caused by an abnormality of the alpha5(IV) antigen along the GBM.

PMID- 12218304
TI  - D-glucose and NaCl enhance the expression of aquaporin-1: inhibition of both by
      cholera toxin.
AB  - AIM: To determine whether glucose, NaCl and/or cholera toxin modify the
      expression of aquaporin-1 (AQP-1) water channel. METHODS: Aquaporin-1 gene
      expression was studied using primary cultures of human renal proximal tubule
      epithelial (HRPTE) cells. RESULTS: D-Glucose and NaCl (500 mosm/kg.H(2)O each)
      enhanced AQP-1 expression 2.4-fold (p < 0.05) and 4.0-fold (p < 0.01),
      respectively, which could be blocked 73 and 70% (p < 0.01), respectively, by
      cholera enterotoxin (10(-7) M). Angiotensin II (10(-6) M and 10(-8) M),
      vasopressin (10(-8) M) and/or atrial natriuretic peptide (10(-8) M) did not
      affect AQP-1 expression. Hyperosmolar Reno-60 and Hypaque-76 contrast agents at
      500 mosm/kg.H(2)O and isomolar Visipaque at 25% (v/v) concentration(s) also
      increased AQP-1 expression 3.8- to 5.0-fold (p < 0.01) in HRPTE cells which also
      were inhibited by cholera toxin from 41% (p < 0.05) to 71% (p < 0.01). AQP-1 was
      translocated from the cytosol to the membrane of HRPTE cells and hyperosmolarity
      enhanced this translocation 2.5-fold (p < 0.01). CONCLUSIONS: The increased
      urinary concentrating ability in proximal segment of the diabetic kidney
      associated with increased plasma glucose may be mediated via glucose's ability to
      enhance AQP-1 expression, which leads to a more concentrated urine. The decrease
      in urinary flow secondary to cholera toxin exposure, on the other hand, may be
      mediated indirectly by cholera toxin's inhibition of aquaoporin-1 gene
      expression.

PMID- 12218305
TI  - Apoptosis and myofibroblast expression in human glomerular disease: a possible
      link with transforming growth factor-beta-1.
AB  - BACKGROUND/AIMS: The pathophysiological pathways involved in the pathogenesis and
      evolution of renal fibrosis, have not been fully elucidated. Transforming growth
      factor-beta(1) (TGF-beta(1)) is involved in the development of renal scarring.
      Apoptosis is responsible for intrinsic cell deletion observed in end-stage kidney
      disease. Myofibroblasts are involved in the development of renal fibrosis. This
      study investigates whether there is a potential relationship between apoptosis,
      myofibroblast infiltration and TGF-beta(1) expression in the kidney of patients
      with glomerulonephritis (GN). METHODS: Forty patients with various types of GN
      were included in the study. Myofibroblasts and TGF-beta(1) positive cells were
      detected in kidney biopsies by immunohistochemistry, while apoptotic cells were
      detected by the in situ end labelling of fragmented DNA. RESULTS: Myofibroblasts
      were identified in the glomeruli of some patients with severe
      mesangioproliferative GN and glomerulosclerosis but a more intensive
      myofibroblast expression was found in the renal interstitium. TGF-beta(1) was
      expressed in the cytoplasm of tubular epithelial cells, in the renal interstitium
      and in the glomeruli of patients with GN. Apoptotic cells were mainly detected in
      the tubules and interstitium and were present in areas with intense myofibroblast
      infiltration. Positive correlations were observed between the intensity of
      myofibroblast expression in the interstitium and apoptosis in the
      tubulointerstitial area (r = 0.521, p < 0.01) as well as TGF-beta(1) expression
      (r = 0.462, p < 0.05) and degree of renal impairment (r = 0.430, p < 0.05).
      CONCLUSIONS: These observations suggest that myofibroblast infiltration and
      apoptosis along with TGF-beta(1) expression are associated with the development
      of interstitial fibrosis in patients with glomerular disease.

PMID- 12218306
TI  - Effective antibiotic treatment of methicillin-resistant Staphylococcus aureus
      associated glomerulonephritis.
AB  - BACKGROUND: A new type of glomerulonephritis following a methicillin-resistant
      Staphylococcus aureus (MRSA) infection has been reported. The purpose of this
      study is to elucidate the clinicopathological features and the responsiveness to
      treatment of the disease. METHODS: We studied the treatment of 8 patients with
      glomerulonephritis related to MRSA infection. We observed the eight cases and
      analyzed clinical features, laboratory findings and histopathological data.
      RESULTS: On admission, all patients had no renal abnormalities. One to four
      months after suffering from MRSA infection, severe proteinuria and hematuria
      developed. Renal biopsy specimens revealed moderate to severe mesangial
      proliferative glomerulonephritis with various degrees of crescent formation.
      Immunofluorescence studies showed IgA and C3. Antibiotic therapy was performed in
      six cases, resulting in successfully reducing the proteinuria in parallel with
      the decreased activity of MRSA infection in five cases. The other 2 cases
      received corticosteroid treatment after complete cessation of MRSA infection, but
      they had a relapse of MRSA infection and later died from sepsis. CONCLUSIONS:
      These results suggested that MRSA-associated glomerulonephritis might respond to
      antibiotic treatment in most cases. This also indicated that special care must be
      taken in the application of steroid therapy for the glomerulonephritis with
      crescents, even though the MRSA infection has gone into an inactive state.

PMID- 12218307
TI  - Cross-linked C-terminal telopeptide of type I collagen in serum before and after
      treatment with alfacalcidol and calcium carbonate in early and moderate chronic
      renal failure.
AB  - The diagnosis of renal osteodystrophy (RO) in chronic renal failure (CRF) in
      everyday practice depends on noninvasive methods. Still there is no widely
      accepted bone resorption marker in RO. The aim of the study was to evaluate the
      correlation of serum cross-linked C-terminal telopeptide of type I collagen (s
      CTx) as the resorption marker with clinical and biochemical data and to evaluate
      s-CTx level changes after treatment with low dose of alfacalcidol and calcium
      carbonate. Sixty patients (36 men and 24 women) with creatinine serum level 3.0
      +/- 1.5 mg% were examined. The result of s-CTx was normal in 27 patients and
      increased in 33. There was a significant positive correlation of s-CTx and serum
      creatinine (p < 0.001), alkaline phosphatase activity (p < 0.05) and duration of
      CRF (p < 0.05) in men and serum creatinine (p < 0.001) and phosphorus (p < 0.05)
      in postmenopausal women. Patients with increased s-CTx had significantly higher
      serum creatinine (p < 0.001), phosphorus (p < 0.01), alkaline phosphatase
      activity (p < 0.001) and longer duration of CRF (p < 0.001) than patients with
      normal s-CTx. Next, 25 patients were treated for 6 months with alfacalcidol in
      dose of 0.25 microg every other day and calcium carbonate in dose of 3.0 microg
      per day and 25 patients with calcium carbonate only. There was a statistically
      significant decrease of s-CTx in both groups of patients (p < 0.01). We conclude,
      that in patients with CRF, s-CTx can be taken as the marker of bone resorption
      changes after treatment of RO but the value of s-CTx as a diagnostic marker in
      these patients ought to be evaluated in comparison with histomorphometry.

PMID- 12218308
TI  - Urinary levels of macrophage migration inhibitory factor in patients with IgA
      nephropathy.
AB  - BACKGROUND/AIM: The processes involved in development of IgA nephropathy (IgAN)
      are not yet well understood. Macrophage migration inhibitory factor (MIF) is a
      potent pro-inflammatory cytokine and is an essential component of immune and
      inflammatory responses. To examine further the possible role of MIF in IgAN, we
      measured MIF levels in the urine. The purpose of the present study was to
      evaluate the involvement of MIF in IgAN. METHODS: Urine samples were obtained
      from 20 IgAN patients. The disease controls included 20 patients with minimal
      change nephrotic syndrome (MCNS). A group of healthy subjects served as control.
      The samples were assayed for MIF protein by a sandwich enzyme-linked
      immunosorbent assay (ELISA). RESULTS: The MIF levels in the urine of patients
      with IgAN examined were significantly higher than those of the healthy control
      subjects. In contrast, the levels of urinary MIF (uMIF) in patients with MCNS did
      not differ significantly from normal values. In IgAN patients, uMIF significantly
      correlated with the magnitude of proteinuria, but not with the grade of
      hematuria. We also investigated the relationship between uMIF levels and
      pathological features. Among patients with IgAN, uMIF levels were significantly
      correlated with the grade of glomerular crescent formation and that of mesangial
      cell proliferation. There was also a significant correlation between uMIF levels
      and the number of both intraglomerular and interstitial macrophages. CONCLUSION:
      Although the underlying mechanisms remain to be determined, these data provide
      evidence that urinary excretion of MIF is increased in IgAN patients with active
      renal lesions.

PMID- 12218309
TI  - Experience with the use of an iron polymaltose (dextrin) complex given by single
      total dose infusion to stable chronic haemodialysis patients.
AB  - BACKGROUND: Many studies of anaemia in patients on chronic haemodialysis have
      noted a high prevalence of iron deficiency despite oral iron supplementation. Our
      study examined the effect of intravenous iron given as bolus replacement. As the
      majority of these patients were not receiving concurrent recombinant human
      erythropoietin (rhEPO) it allowed an analysis of the safety and efficacy of
      intravenous iron as a single agent. METHODS: All patients with a haemoglobin
      level of less than 10 g/dl and considered iron deficient by the finding of a
      percentage transferrin saturation of less than 20% were given intravenous iron in
      the form of iron polymaltose (dextrin) by total dose infusion (TDI). The dose was
      calculated from tables supplied by the manufacturers. Patients with serum
      ferritin levels in excess of 225 ng/ml were excluded. RESULTS: In our unit, 62
      out of 80 (77%) patients were considered iron deficient and received IV iron. Ten
      (10%) were considered to be in iron balance and 8 (10%) had biochemistry
      suggesting iron overload. None of the patients receiving iron experienced any
      adverse reactions. At three months a rise in haemoglobin level of at least 1 g/dl
      was noted in 53% of patients. The response was less in the remainder, but only 2
      showed no response. CONCLUSIONS: Low levels of iron deficiency are often
      unrecognized in chronic haemodialysis patients on conventional therapy including
      oral iron supplementation. In such patients, the use of total dose infusion of
      iron polymaltose (dextrin) is a safe and effective method of raising haemoglobin
      levels. Substantial improvements may be achieved without the concurrent use of
      rhEPO.

PMID- 12218310
TI  - Home hemodialysis. Revival of a superior dialysis treatment.
AB  - BACKGROUND: Home hemodialysis is usually considered a superior therapy, whose
      decline is related to demographic, social, psychological and financial factors as
      well as to competition with renal transplantation and PD. METHODS: A home
      hemodialysis program was started in November 1998 in the University of Torino,
      Italy (200-210 patients on dialysis). Its main features are the tailoring of
      dialysis schedules and the acceptance of patients with comorbidity. Nurses assist
      home sessions in case of short-term problems, while the training center ensures
      follow-up for long-term clinical and logistic problems. RESULTS: The program
      started in November 1998 on a previous one (active from 1970 to 1998; 6 patients
      on treatment in November 1998). Since then, 25 more patients joined the program.
      Out of 31 patients followed since November 1998, 4 were grafted, 2 died, and 2
      dropped out from training. In June 2001, 15 patients were on home hemodialysis, 8
      on training. Dialysis schedules and controls are flexible and tailored; in June
      2001, range of dialysis time was 1.20-5 h; sessions: 2-6; 8 patients were on
      thrice-weekly dialysis, 7 on daily dialysis; all patients reached target EKRc >10
      ml/min (median 15, range 11-24 ml/min). CONCLUSION: Tailored, flexible schedules
      allowed home hemodialysis in over 10% of our patients, confirming that there is
      still room for this treatment in our setting.

PMID- 12218311
TI  - Plasma neuropeptide Y concentrations in patients on hemodialysis.
AB  - BACKGROUND: Neuropeptide Y (NPY) is a 36-amino-acid peptide that was originally
      isolated from the porcine brain. NPY, in contrast to leptin, is one of the most
      potent appetite stimulants. In some previous studies, NPY was found to be
      correlated with mean blood pressure (MBP) and fluid volume in patients on
      hemodialysis (HD), contributing to volume-induced hypertension. However, it is
      still unclear which NPY-sensitive neuronal pathways are responsible for the
      various changes seen in response to central NPY administration. In this study we
      analyzed the correlation of circulating levels of NPY with parameters of
      nutritional conditions, and we investigated the relationships between NPY
      concentrations and clinical markers of fluid volume in patients on HD. We also
      evaluated the effects of high-flux dialysis membranes on plasma NPY levels as
      compared with those of low-flux membrane. METHODS: Plasma NPY concentrations in
      patients on regular HD were measured using commercially available
      radioimmunoassay (RIA) kits. We examined the relationship between plasma NPY
      concentration and other clinical indices in patients on HD. RESULTS: Plasma NPY
      concentrations were inversely correlated with the serum urea nitrogen levels (r =
      -0.32) as well as protein catabolic rate (PCR) (r = -0.28). Plasma NPY was also
      correlated with the increase in body weight between HD sessions (r = 0.29). On
      the other hand, plasma NPY concentrations were not correlated with MBP, atrial
      natriuretic peptide (ANP), or adrenomedullin (AM). The reduction rate of plasma
      NPY with a high-flux dialysis membrane was significantly higher than that with a
      low-flux dialysis membrane. CONCLUSIONS: The secretion of NPY may be enhanced in
      a poor state of nourishment and stress induced by fluid volume overload in
      patients on HD, and plasma NPY is removed by a high-flux dialyzer.

PMID- 12218312
TI  - Cyclosporin A toxicity of the renal allograft--a late complication and
      potentially reversible.
AB  - Cyclosporin A (CsA) has improved patient and organ graft survival, but the
      dichotomy of benefit and toxicity is still an issue. In a retrospective analysis
      of 392 renal transplant recipients we documented CsA nephrotoxicity (striped
      fibrosis, arteriolar wall hyalinosis) in 28 (7.1%) patients (23 male/5 female) in
      a follow-up of more than one year post transplantation. Median age at renal
      transplantation was 41 years (13-60) and the period between transplantation and
      graft biopsy was 42 months (12-122). Median CsA trough levels (ng/ml) at 12
      months post transplantation, at time of graft biopsy and at last follow-up were:
      114 (71-265), 130 (78-285), 66 (24-115). The following parameters were assessed
      at 12 months post transplantation, at time of biopsy and at last follow-up: s
      creatinine (micromol/l), Doppler resistive index, systolic and diastolic blood
      pressure (mm Hg) and the number of antihypertensives. Median s-creatinine at 12
      months post transplantation was 150.3 (94.6-247.5), at biopsy 225.4 (121.1-353.6)
      and at last follow-up 160.0 (106.1-247.5) (p < 0.001 for biopsy vs. last follow
      up). Resistive index decreased from 0.70 (0.64-0.88) to 0.68 (0.51-0.84) (p <
      0.005), systolic blood pressure from 137 (100-168) to 130 (105-144) (p < 0.05)
      and the number of patients with more than 4 antihypertensives from 10 to 6
      between biopsy and last follow-up, with no acute rejection episodes after
      modification of immunosuppressive therapy (50% of previous CsA trough level and
      addition of azathioprine or mycophenolate mofetil). CONCLUSION: CsA
      nephrotoxicity occurs late after renal transplantation with increased systolic
      blood pressure and Doppler resistive index. Reduction of CsA improves renal
      function, reduces graft resistive index and systolic blood pressure.

PMID- 12218313
TI  - Altered expression of Na(+)/H(+) exchanger isoforms 1 and 3 in clipped and
      unclipped kidneys of a 2-kidney-1-clip Goldblatt model of hypertension.
AB  - BACKGROUND: Functional differences between the clipped and unclipped kidneys in a
      2-kidney-1-clip (2K-1C) hypertension model have been reported. However, the
      molecular basis of these changes is poorly understood. OBJECTIVES: Expression of
      NHE-1 and NHE-3 isoforms and sodium pump activity (PNP), and their modulation by
      blood pressure (BP), PGE(2) and TXB(2) were examined in the kidneys of 2K-1C rats
      treated with cilazapril for short- (4 and 24 h) and long-term (7 days) periods.
      METHODS: 2K-1C rats were divided into two groups. Group 1 (short-term) animals
      were treated with a single dose of cilazapril for 4 or 24 h. Group 2 (long-term)
      animals received a daily dose of cilazapril for 7 days. 2K-1C animals receiving
      water served as clipped controls, and sham-operated animals were normal controls.
      Western blot analysis was used to estimate the protein levels and ELISA for
      PGE(2) and TXB(2). RESULTS: Levels of NHE-1 and NHE-3 protein in the unclipped
      kidneys of both treatment groups were increased, whereas levels of alpha-actin,
      PNP activity and crude microsomes remained unchanged. These changes were
      significantly reduced by long-term, and not by short-term treatment with
      cilazapril. In group 1 clipped kidneys, NHE-3 and alpha-actin proteins were
      increased, and crude microsomes and PNP activity were decreased. In group 2
      clipped kidneys, both NHE-1 and 3 isoforms were induced, whereas PNP activity was
      decreased. Cilazapril did not reverse the changes in the clipped kidneys in both
      groups, but reduced the crude microsomes. Group 2 unclipped kidneys showed
      hypertrophy, which remained unaffected by cilazapril treatment. Induced levels of
      BP, PGE(2) and TXB(2) in both groups were reduced significantly except for the 24
      hour post-cilazapril treatment. CONCLUSIONS: These findings demonstrate a
      differential expression of NHE-1 and NHE-3 isoforms which is dependent on the
      rise in BP, PGE(2) or TXB(2) in the long-term treatment group, but not in the
      short-term treatment group. Thus, the changes in NHE isoforms and sodium pump
      activity, together, contribute to functional differences that exist in the 2K-1C
      kidneys.

PMID- 12218314
TI  - Site of methylguanidine production and factors that influence production levels.
AB  - The site of methylguanidine (MG) production in the kidney was investigated using
      animal models of renal disease and cultured renal epithelial cells. In rats with
      proximal tubular injury induced by adenine, the blood and urinary levels of MG
      increased as the severity of injury increased. In contrast, in cases of
      glomerular injury, there were no such changes in MG levels. Thus, it was apparent
      that proximal tubular injury served to promote MG production. In addition, a
      marked increase was observed in the intensities of bands attributable to 5,5
      dimethyl-1-pyrroline-N-oxide (DMPO)-OH in the electron spin resonance spectrum of
      the kidney in the rats given adenine. In these rats, the activity of the radical
      scavenging enzymes superoxide dismutase, catalase, and glutathione peroxidase was
      decreased. This suggests that the formation of excessive radicals and
      deterioration of defense mechanisms that contribute to the development of
      oxidative stress underlie the enhanced MG production. The experiments using
      cultured cells revealed that an oxide of adenine, 2,8-dihydroxyadenine (DHOA),
      directly induced renal tubular injury. These findings indicate that the
      accumulation of creatinine due to DHOA, combined with oxidative stress, resulted
      in increased MG production.

PMID- 12218315
TI  - Renal prostacyclin biosynthesis in a baboon model of Shiga toxin mediated
      hemolytic uremic syndrome.
AB  - BACKGROUND/AIMS: Shiga toxin (Stx) and lipopolysaccharide (LPS) both participate
      in the pathogenesis of post-diarrheal (D+) hemolytic uremic syndrome (HUS), but
      little is known about factors that modulate the host response to these toxins.
      Prostacyclin (PGI(2)) is a potent renal vasodilator and inhibitor of platelet
      aggregation and adhesion. An inability to produce PGI(2) in response to
      endothelial cell injury could drive the pathogenic cascade. We therefore used a
      baboon model of HUS to measure PGI(2 )production following the administration of
      Stx and LPS. METHODS: Shiga toxin-1 (Stx-1), with and without LPS, was
      administered intravenously to baboons in various doses and schedules. 6-keto
      PGF(1)alpha, the stable metabolite of PGI(2), was measured by ELISA in the plasma
      and urine. RESULTS: Plasma concentrations did not change significantly. Urine
      values increased significantly in some groups, but not in others, and HUS
      developed both in animals that did and did not exhibit a significant increase in
      urinary PGI(2) production. CONCLUSIONS: Renal PGI(2) biosynthesis appears to be
      affected by the dose and rate of Stx administration, and the timing of LPS
      infusion. PGI(2) does not protect our primate model from developing HUS.

PMID- 12218316
TI  - Enhanced Dendroaspis natriuretic peptide immunoreactivity in experimental
      ureteral obstruction.
AB  - Whether the postobstructive diuresis can in part be related to an altered
      regulation of Dendroaspis natriuretic peptide (DNP) was investigated. Male
      Sprague-Dawley rats were bilaterally obstructed of their ureters. Control group
      was with sham ureteral obstruction. Forty-eight h later, tissue levels of DNP
      immunoreactivity were determined in the plasma, heart, and kidneys. Urine samples
      were collected in some rats under anesthesia. The plasma DNP immunoreactivity was
      significantly increased by 45% in the experimental group. The tissue levels of
      DNP immunoreactivity in the atrium, ventricle, or kidneys did not significantly
      differ between the experimental and control groups. The urinary flow and sodium
      excretion rate were 3- to 4-fold increased in the experimental group. The urinary
      DNP excretion was also increased in the experimental group, which was positively
      correlated with the urinary volume and sodium excretion. The urinary excretion of
      cGMP was 2- to 3-fold increased in the experimental group. These results indicate
      that an enhanced DNP activity may in part be causally related to the
      postobstructive diuresis.

PMID- 12218317
TI  - Changes in urinary levels and renal expression of uroguanylin on low or high salt
      diets in rats.
AB  - BACKGROUND: The novel peptide, uroguanylin, is mainly produced in the intestine
      and causes natriuresis via cyclic GMP (cGMP) activation. Uroguanylin plays an
      important role in sodium transport in the gastrointestinal tract and functions as
      an intestinal natriuretic hormone during oral salt load. However, the role and
      behavior of uroguanylin in the kidneys during high salt load remains unknown.
      METHODS: We measured the uroguanylin concentrations in the urine and plasma of
      rats fed with low or high salt diets for 1 week, using a sensitive
      radioimmunoassay (RIA). Urinary cGMP and electrolyte excretion was also measured.
      Intestinal and renal expression of uroguanylin mRNA was evaluated by Northern
      blotting and by reverse transcription-polymerase chain reaction (RT-PCR).
      RESULTS: The urinary excretion of immunoreactive (ir-) uroguanylin in rats on the
      high salt diet was significantly higher than that in the low salt group (425 +/-
      107 vs. 128 +/- 8.5 pmol/day, p < 0.01) and significantly correlated with urinary
      Na(+) and cGMP excretion. Plasma ir-uroguanylin levels between the two groups did
      not significantly differ. Uroguanylin mRNA expression was increased both in the
      intestine and kidneys of rats on the high salt diet. CONCLUSION: These findings
      suggest that uroguanylin regulates sodium metabolism in the intestine and kidneys
      during oral salt load in an autocrine and paracrine manner.

PMID- 12218318
TI  - Fibronectin splice variants--prognostic markers for the stage of renal
      interstitial fibrosis in the rat.
AB  - BACKGROUND/AIMS: Renal interstitial fibrosis (RIF) is the main cause for
      progressive renal failure, but its pathogenic factors are not well known. In
      animal models of renal fibrogenesis done thus far an increase of total
      fibronectin (FN) mRNA has been proved. Recent studies have pointed to a key role
      of the splice variant EIIIA(+)-FN and EIIIB(+)-FN for the development of organ
      fibrosis. However, a broader knowledge of the distribution of these different FN
      mRNA isoforms is still lacking. Our aim was to study the particular expression of
      the EIIIA(+)-FN and EIIIB(+)-FN during the process of fibrogenesis in two rat
      models and to evaluate the FN isoforms as diagnostic/prognostic marker for the
      stage of interstitial damage in rat kidneys. METHODS: Kidneys of unilateral
      ureteral obstruction (UUO) and control rats were removed in intervals of 5, 14 or
      21 days after surgery. For the investigation of kidney damage due to uranyl
      nitrate (UN), rats obtained a single i.p. dose of 5 mg/kg body weight UN and were
      killed 2, 10 and 20 weeks thereafter. The quantitative RT-PCR method was used to
      estimate the total FN, EIIIA(+)-FN and EIIIB(+)-FN transcription rate. RESULTS:
      In the UUO model, a significant augmentation of both isoforms was obtained in the
      kidneys in the first 5-day interval, which was more pronounced at the 21-day
      interval. In the UN-treated kidneys there appeared only a continuous increase of
      EIIIA(+)-FN and the splice variant EIIIB(+)-FN failed to show a shift in these
      animals as compared to the controls. CONCLUSION: Both animal models generated
      fibrogenic damages of the tubulointerstitium, whereas only the UUO resulted in
      progressive fibrosis. Absence of EIIIB(+)-FN seems to enhance the progression of
      fibrogenesis.

PMID- 12218319
TI  - Heminephrectomy causes the progression of glomerulosclerosis and apoptosis in
      high IgA strain ddY mice.
AB  - BACKGROUND: The reduction in nephrons in IgA nephropathy is critical to the
      prognosis of this disease. However, the immunopathological mechanism of the
      modifications seen in glomerular lesions is not clear. We thus investigated the
      influence of nephron reduction by heminephrectomy on renal lesions in a high
      immunoglobulin A inbred strain of ddY mouse (HIGA mouse), which shows progressive
      mesangial sclerosis with elevated renal expression of transforming growth factor
      (TGF)-beta. METHODS: Five-week-old HIGA mice were heminephrectomized (Nx), and
      were evaluated in comparison with a sham-operated group (S) at 40 weeks old.
      Histological findings, immunoglobulin depositions (IgG, IgA, and IgM), and
      expressions of cytokine and extracellular matrix proteins (TGF-beta, fibronectin,
      collagen type I and IV) were analysed. PCNA and TUNEL stainings were performed
      with electron microscopic detection of apoptosis. Tissue renin-angiotensin
      systems (RAS) were also investigated by real-time quantitative RT-PCR. RESULTS:
      In the Nx group, the glomerular tuft area and ratio of mesangial matrix area per
      tuft were significantly increased, and the glomerular cell count per tuft area
      was significantly decreased. Glomerular immunoglobulin deposits of IgG, IgA, and
      IgM in Nx were all significantly expanded in the paramesangium. The glomerular
      expressions of TGF-beta and the extracellular matrix proteins were significantly
      increased in Nx mice. In contrast to the significant decrease of PCNA-positive
      cells, TUNEL-positive cells were significantly increased in Nx. Angiotensin
      converting enzyme (ACE) was significantly increased in the renal cortex of Nx.
      CONCLUSION: Simple heminephrectomy, other than 5/6 renal ablation, of HIGA mice
      may be a potential model for research into the progressive glomerulosclerosis of
      human IgA nephropathy. The pathological role of apoptosis is apparently involved
      in these disease processes, possibly through upregulated RAS.

PMID- 12218320
TI  - Effect of oral adsorbent (AST-120) on renal function, acquired renal cysts and
      aortic calcification in rats with adriamycin nephropathy.
AB  - AIMS: The effect of oral adsorbent, AST-120, on the experimental renal disease
      induced by adriamycin, uninephrectomy and high protein diet proposed as a model
      of acquired cystic disease of the kidney was investigated. METHODS: 3 mg of
      adriamycin was injected into the tail vein of rats and 4 weeks later right-side
      nephrectomy was performed, 2 weeks thereafter 26 rats with urinary protein
      excretion between 100 and 358 mg/day were selected from 60 rats. Two groups, 13
      rats in each group, namely the AST-120-treated group and control group, both of
      which had equal renal damage before the administration of AST-120 or placebo. AST
      120 (0.4 g/100 g BW/day) was administered for 19 weeks. RESULTS: Serum creatinine
      and BUN in the AST-120-treated group were significantly lower (serum creatinine:
      3.3 +/- 2.1 vs. 7.1 +/- 2.7 mg/dl, p < 0.003) and creatinine clearance was higher
      (0.62 +/- 0.49 vs. 0.29 +/- 0.30 ml/min, p < 0.05) at the final examination than
      in the control group. Survival rate which was examined using another set of 9
      rats was higher in AST-120-treated rats than in AST-120-untreated rats. Serum
      indoxyl sulfate was significantly lower at all times after using AST-120 in the
      AST-120-treated group than in contrast to the control group. Histological
      examination revealed less severe interstitial and cystic changes in the AST-120
      treated group. This suggests that AST-120 can prevent or retard the development
      of acquired renal cystic disease in this model. Aortic calcification tended to be
      less severe in the AST-120-treated group because of less serum Ca x P products.
      CONCLUSION: The AST-120-treated group significantly decreased serum creatinine
      and increased creatinine clearance with less severe renal cystic changes in this
      model during the later weeks of administration of AST-120 or at death,
      accompanied with the tendency of less severe aortic calcification.

PMID- 12218321
TI  - Hemolysate pretreatment ameliorates ischemic acute renal injury in rats.
AB  - Heme oxygenase-1 (HO-1) is an antioxidant enzyme and is believed to protect
      against oxidative stress-induced tissue injury. Renal ischemia-reperfusion (IR)
      injury seems at least in part to be caused by the oxidative stress. The aim of
      this study was to improve the renal IR injury by clinically available means. When
      littermate hemolysate was intravenously administered into rats, HO-1 was markedly
      induced in the kidneys. To investigate whether prior induction of HO-1 by the
      hemolysate injection ameliorates the subsequent renal IR injury, we assessed the
      levels of blood urea nitrogen (BUN) and serum creatinine (SCr), markers for renal
      injury, in rats with 45 min of ischemia followed by 18 h of reperfusion. To avoid
      the nephrotoxicity induced by hemolysate, small but effective amounts of
      hemolysate was injected into rats at 48 h prior to the ischemia. The levels of
      BUN and SCr values were significantly improved as compared to the rats with renal
      IR injury alone. Administration of HO inhibitor abolished the efficacy of
      hemolysate pretreatment. Our findings indicated that the prior induction of HO-1
      by treatment of littermate hemolysate ameliorated the subsequent renal IR injury.
      Prior injection of self-hemolysate would be clinically useful for the protection
      against the renal IR injury induced by kidney transplantation and kidney surgery
      without immunological and infectious problems.

PMID- 12218322
TI  - A model of isolated autologously hemoperfused porcine slaughterhouse kidneys.
AB  - BACKGROUND: The rapidly evolving field of transplantation research with a focus
      on ischemic and reperfusion injuries has gained importance since the methodology
      of organ preservation significantly limits graft survival. Numerous models of
      isolated perfused kidneys have been established in the past years but limitations
      such as organ size, perfusate and ethical standards have restricted a widespread
      research in this area. METHODS: A model of hemoperfused isolated porcine
      slaughterhouse kidneys was established which encompasses the advantages of
      autologous blood as optimal perfusate and a reduction of animal experiments.
      RESULTS: The size and geometry of the porcine kidney is more comparable to human
      conditions and various renal functions, blood parameters and morphology can
      easily be accessed in the present model. Stable organ function can be maintained
      over 2 h with an amount of 500-1,000 ml of autologous blood which is
      metabolically controlled via a dialysis system. CONCLUSION: In summary, the
      present model describes a new and economic approach for targeting renal function
      in transplantation models by combining autologous blood as optimal perfusate with
      a well-defined organ geometry and function and slaughterhouse animals as a
      source.

PMID- 12218323
TI  - Colchicine suppresses osteopontin expression and inflammatory cell infiltration
      in chronic cyclosporine nephrotoxicity.
AB  - BACKGROUND: Colchicine (Col) is beneficial to renal injury because of its anti
      inflammatory effect, but its mechanism has yet to be elucidated. The present
      study was designed to evaluate the inhibitory effects of colchicine on
      osteopontin (OPN) expression and the macrophage accumulation in chronic
      cyclosporine (CsA) nephrotoxicity in rats. METHODS: Male adult Sprague-Dawley
      rats on a low salt diet (LSD, 0.05% sodium) were treated daily with Col (30
      microg/kg), CsA (15 mg/kg), and both CsA and colchicine or vehicle (olive oil 1
      ml/kg) for 4 weeks. The effects of colchicine on chronic CsA nephrotoxicity were
      evaluated by examining renal function, histopathology, and ED-1 positive cells.
      The expressions of OPN mRNA and protein were estimated respectively by Northern
      blot and immunohistochemistry. RESULTS: Compared with vehicle-treated rats, CsA
      treated rats showed an increase in serum creatinine, a decline in creatinine
      clearance rate, and tubulointerstitial fibrosis (all p < 0.01). Concomitant
      administration of colchicine reversed all of the above parameters (all p < 0.01).
      Of note, the upregulated expression of osteopontin mRNA and protein seen in CsA
      treated rats was significantly decreased after colchicine treatment. Furthermore,
      the expression of osteopontin mRNA was strongly correlated with the number of ED
      1 positive cells (r = 0.712, p < 0.001) and the tubulointerstitial fibrosis score
      (r = 0.586, p = 0.007). CONCLUSION: Colchicine is capable of abrogating the
      upregulation of chemotactic OPN expression and macrophage influx, and this is
      associated with improved renal tubulointerstitial fibrosis in chronic CsA
      nephrotoxicity.

PMID- 12218324
TI  - De novo C1q nephropathy in the renal allograft of a kidney pancreas transplant
      recipient: BK virus-induced nephropathy?
AB  - C1q nephropathy is a distinct entity characterized by extensive and dominant C1q
      mesangial deposition with associated steroid resistant proteinuria in the absence
      of systemic lupus erythematosus. Several morphological patterns ranging from very
      subtle glomerular alterations to focal/segmental glomerulosclerosis and mesangial
      proliferative changes have been described. Interstitial nephritis secondary to BK
      polyomavirus is a recently recognized complication in kidney transplant
      recipients. It may be associated with a tubulitis-like picture, mimicking
      sometimes acute tubular rejection. We report the case of a kidney pancreas
      transplant recipient who developed de novo C1q nephropathy, in the setting of BK
      polyomaviral interstitial nephritis. He presented with renal allograft
      dysfunction and a kidney biopsy was performed. It was interpreted as acute
      cellular rejection. C1q deposits were detected by immunofluorescence studies and
      electron microscopy. The patient did not respond clinically to appropriate anti
      rejection treatment and a second renal biopsy was performed. The possibility of
      an interstitial nephritis secondary to BK polyomavirus mimicking rejection was
      suggested. Special immunohistochemical and blood/urine PCR studies for BK virus
      were performed, confirming the diagnosis of BK virus tubulonterstitial nephritis
      with a persistent, probable BK virus induced C1q nephropathy.

PMID- 12218325
TI  - Epstein-Barr virus-associated acute interstitial nephritis: infection or
      immunologic phenomenon?
AB  - Epstein-Barr virus (EBV) DNA in renal tissue in acute interstitial nephritis (IN)
      has not been previously reported. An 18-year-old male presented with a sore
      throat, fever, cervical lymphadenopathy, and oliguric renal failure. The rapid
      slide test for heterophile antibodies associated with infectious mononucleosis
      was positive, and a renal biopsy showed an acute interstitial nephritis. A
      polymerase chain reaction (PCR) assay identified EBV DNA in the renal biopsy. In
      situ hybridization (ISH) for EBV RNA and immunohistochemistry for latent membrane
      protein 1 of EBV were negative. Hemodialysis and prednisone 60 mg PO OD were
      administered and the s-creatinine dropped from 1,224 to 75 micromol/l over 9
      days. The identification of EBV DNA in the kidney raises the possibility that
      direct infection plays a role in acute IN associated with EBV.

PMID- 12218326
TI  - An atypical pattern of Epstein-Barr virus infection in a case with idiopathic
      tubulointerstitial nephritis.
AB  - Recently, Epstein-Barr virus (EBV) received attention because a latent form of
      its infection in renal proximal tubular epithelial cells was found to cause
      idiopathic, chronic tubulointerstitial nephritis. In this report, we describe the
      case of a patient with a replicative form of EBV infection, chronic active EBV
      infection (CAEBV), who developed acute tubulointerstitial nephritis and minimal
      change nephrotic syndrome. A renal biopsy revealed papillary infoldings of
      atypical tubular epithelium and adjacent dense infiltration of lymphocytes. Using
      in situ polymerase chain reaction methods, we detected the EBV genome in some of
      the infiltrating lymphocytes, but not in the tubular epithelial cells. EBV
      infected T cells are thought to activate other educated T cells, as well as
      secrete an unrestricted variety of cytokines, thus playing a pivotal role in
      CAEBV and its end organ disease. Therefore, in our case, the CAEBV activated,
      educated T cells may have followed the EBV-infected lymphocytes as they
      infiltrated into the peritubular interstitium, and promoted focal tubular
      epithelial atypia and minimal change nephrotic syndrome. The long-term
      observation of such patients is important because CAEBV may progress into
      lymphoproliferative diseases.

PMID- 12218327
TI  - Decrease in urinary excretion of aquaporin-2 associated with impaired urinary
      concentrating ability in diabetic nephropathy.
AB  - Aquaporin-2 (AQP-2) is known to be expressed in the renal collecting duct cells
      and participates in urinary concentration in response to arginine vasopressin
      (AVP). The present study was undertaken to determine whether progression of renal
      dysfunction affects urinary excretion of AQP-2 in diabetic nephropathy. The study
      was composed of 8 control subjects and 14 patients with type 2 diabetes
      classified into two groups according to serum creatinine level (cut-off point;
      1.5 mg/dl). After an 8-hour water deprivation, both urinary osmolality (U(osm))
      and urinary excretion of AQP-2 significantly decreased in the diabetic patients
      with chronic renal failure as compared to the control subjects (p < 0.0001, p <
      0.05, respectively). After a water load (10 ml/kg), no differences were found in
      plasma osmolality (P(osm)), AVP levels and U(osm), whereas urinary excretion of
      AQP-2 significantly decreased in the patients with chronic renal failure as
      compared to the control subjects (p < 0.05). These results indicate that the
      decreased urinary excretion of AQP-2 in diabetic nephropathy is due to the
      impaired cellular signaling of AVP in collecting duct cells, which may be partly
      involved in the urinary concentrating defect in renal failure.

PMID- 12218328
TI  - Methylenetetrahydrofolate reductase polymorphism in childhood primary focal
      segmental glomerulosclerosis.
AB  - AIM: The purpose of this study was to evaluate the association between the
      methylenetetrahydrofolate reductase (MTHFR) C/T polymorphism and the prevalence
      and course of focal segmental glomerulosclerosis (FSGS) in our pediatric
      population. METHODS: Genotypes for MTHFR were determined in 15 primary FSGS
      patients (male/female, 6/9) and 238 control subjects (male/female, 110/128) by
      the polymerase chain reaction and restriction fragment length polymorphism
      method. RESULTS: For the whole group, the genotype frequencies (CC/CT/TT) of
      MTHFR in FSGS and control subjects were almost comparable. The TT genotype was
      associated with early onset of the disease as compared with the CC genotype.
      Furthermore, all the patients with the TT genotype had steroid-resistant FSGS and
      developed into end-stage renal failure, while those carrying either CC or CT
      genotype did not. CONCLUSION: We speculate that the TT genotype may be associated
      with early development and progression of childhood FSGS. Confirmatory studies
      using larger and ethnically distinct populations are needed to reveal the role of
      homocysteine in FSGS with consideration of medical interventions.

PMID- 12218329
TI  - Nephrotic syndrome due to immunologically mediated hypocomplementic
      glomerulonephritis in a patient of Waldenstrom's macroglobulinemia.
AB  - A 72-year-old man was diagnosed as having nephritic syndrome complicated by
      Waldenstrom's macroglobulinemia (WM). A monoclonal IgM lambda protein and
      decreased serum complements were observed. The renal biopsy disclosed the
      capillary occluded by thrombi which was stained with IgG, IgA, IgM, C4, lambda
      light chain and slight kappa light chain in a granular pattern. Electron dense
      deposits were noted in the subendothelial spaces. An unusual case of WM who
      developed nephrotic syndrome due to immunologically mediated hypocomplementic
      glomerulonephritis is described.

PMID- 12218330
TI  - Crescentic glomerulonephritis in a patient with heterozygous Fabry's disease.
AB  - A 58-year-old woman who suffered from a heterozygous Fabry's disease and immune
      complex crescentic glomerulonephritis (GN) is reviewed. The diagnosis was made on
      the basis of the pathologic findings and peripheral leukocyte alpha-galactosidase
      activity. Light microscopy revealed a vacuolization of epithelial cells and
      electron microscopy showed myelin figures in the cytoplasm of visceral epithelial
      cells typical of Fabry's disease at the first renal biopsy. During the following
      4 months she developed progressive renal failure and a second renal biopsy
      disclosed the formation of cellular crescents in 7 of 11 glomeruli observed. A
      rare case of combined Fabry's disease and crescentic glomerulonephritis is
      discussed.

PMID- 12218331
TI  - Role of ribavirin in membranoproliferative glomerulonephritis associated with
      hepatitis C virus infection refractory to alpha-interferon.
AB  - Chronic hepatitis C virus (HCV) has been associated with several extrahepatic
      diseases, such as membranoproliferative glomerulonephritis (MPGN). alpha
      Interferon is currently the treatment of choice for this association. When this
      therapy fails clinicians face a difficult challenge due to the lack of useful
      information in these particularly difficult patients. We report the case of a
      severe nephrotic syndrome due to MPGN associated HCV infection, in which a triple
      association--interferon plus ribavirin and cyclophosphamide--was needed to
      control the disease.

PMID- 12218332
TI  - Saethre-Chotzen syndrome presenting with incomplete renal Fanconi syndrome.
AB  - Here we report on a patient with findings of acrocephaly, craniosynostosis, low
      frontal hairline, ptosis of eyelids, deviated nasal septum, broad great toes,
      moderate hallux valgus, bilateral symmetrical complete soft tissue syndactyly of
      toes 2 and 3, and partial soft tissue syndactyly of toes 4 and 5 consistent with
      the diagnosis of Saethre-Chotzen syndrome. Additionally, the patient had some
      unusual findings as part of generalized dysfunction of the renal tubules
      including hypophosphatemia with renal phosphate wasting, normocalcemic
      hypercalciuria, hypomagnesemia with renal magnesium wasting, low-molecular-weight
      proteinuria, decreased serum PTH levels, osteopenia, and nephrolithiasis. In the
      light of these findings, the diagnosis of incomplete renal Fanconi syndrome was
      made. In conclusion, on the basis of the present findings, it is difficult to say
      whether renal tubular dysfunction are somehow connected to the Saethre-Chotzen
      syndrome or not. Therefore, we consider that this is probably just a coincident.
      However, further studies may show the connection between renal tubular
      dysfunction and Saethre-Chotzen syndrome.

PMID- 12218333
TI  - Lymphopenia in Wegener's granulomatosis. A new clinical activity index?
AB  - BACKGROUND: Significant lymphopenia is a prominent feature in systemic
      erythematous lupus, but has not been described in Wegener's granulomatosis (WG).
      We suggest from a retrospective analysis that lymphopenia may also be an index of
      WG disease activity. METHODS: Medical charts form 19 patients diagnosed with
      systemic active WG between 1990 and 2000 were reviewed retrospectively. All
      patients had crescentic glomerulonephritis and alveolar hemorrhage. Clinical and
      biological markers were reviewed at three different time points: diagnosis, time
      of relapse, and during remission. RESULTS: Average lymphocyte count was
      significantly lower at diagnosis and relapse than during remission times (p <
      0.008 and p < 0.000002, respectively). During disease activity either at
      diagnosis and during relapses, ANCA titers were highly positive (> or =50 IU/ml)
      in 27.5% of patients (8/29). The corresponding lymphocyte counts were below
      normal (1,500/min(3)) in 28 of 29 patients (96.5%). In patients with either
      negative or weakly positive ANCA, mean lymphocyte count was 728.5, 744.2 and
      2,551/ml at diagnosis, during relapse and remission times, respectively. There
      was a clear negative correlation between the lymphocyte count and disease
      activity. CONCLUSION: Lymphopenia appears to be a good marker of WG activity.
      This index might be useful in all patients including those with negative ANCA.

PMID- 12218334
TI  - Reciprocal expression of vascular endothelial growth factor and nitric oxide
      synthase by coronary arterial wall cells during chronic inhibition of nitric
      oxide synthesis in rats.
AB  - Chronic inhibition of nitric oxide (NO) synthesis by oral administration of N(G)
      nitro-L-arginine methyl ester (L-NAME) causes hypertension and produces
      arteriosclerosis in rats. Balloon injury induces upregulation of vascular
      endothelial growth factor (VEGF) in medial smooth muscle cells of the rat
      arterial wall, and NO secreted by a restored endothelium acts as the negative
      feedback mechanism that downregulates VEGF expression to basal levels. In this
      study, we tested the hypothesis that a reciprocal relation between VEGF and NO
      would be established in a rat model of chronic NO blockade. Male Wister rats
      received plain drinking water (n = 10) or L-NAME (0.5 mg/ml) in the drinking
      water (n = 11) for 6 weeks. After 6 weeks, the wall-to-lumen ratios and
      perivascular fibrosis in the coronary arteries were greater in the L-NAME group
      than in the control group. NO synthase-positive cells in the intima were
      abundantly observed in the control group, whereas no such cells were seen in the
      L-NAME group. In contrast, the number of VEGF-positive smooth muscle cells in the
      media was greater in the L-NAME group than in the control group. These findings
      strongly suggest a reciprocal relation between VEGF and NO even in a rat model of
      chronic NO blockade.

PMID- 12218335
TI  - Renal vein and inferior vena cava thrombosis associated with acute pancreatitis.
AB  - Renal vein thrombosis (RVT) is a well-recognized complication of the nephrotic
      syndrome, but it is extremely rare in patients with acute pancreatitis. Vascular
      thrombosis complicating pancreatitis is thought to be due to release of
      proteolytic enzymes from the pancreas and direct vasculitis. Peripancreatic
      vessels are most commonly involved in the complications associated with
      pancreatitis. Renal vein and inferior vena cava (IVC) thrombosis, however, is an
      exceptionally rare complication of pancreatitis. Awareness of this complication
      will help physicians in its early diagnosis and management. We report a case of
      renal vein and IVC thrombosis in a patient with acute pancreatitis.

PMID- 12218336
TI  - Is isoniazid ototoxic in patients undergoing hemodialysis?
AB  - Drug-induced ototoxicity might sometimes be a problem in end-stage renal failure
      (ESRF) patients. However, ototoxicity secondary to isoniazid intake has not been
      reported in ESRF until now. During the last decade, ototoxicity was diagnosed in
      16.6% (7/42) of our ESRF patients undergoing hemodialysis (HD) who also used
      antituberculosis therapy. Streptomycin was not included in any of these regimens,
      isoniazid was used by all 7 patients with ototoxicity and there was reversal of
      hearing loss in 2 of these patients after discontinuation of isoniazid. In our
      ESRF-HD patients who developed ototoxicity during the course of antituberculosis
      therapy, isoniazid was probably the responsible agent either alone or it added to
      the side effects of other drugs.

PMID- 12218337
TI  - Sclerosing encapsulating peritonitis: regional changes of peritoneum.
AB  - Sclerosing encapsulating peritonitis (SEP) is characterized by the diffuse
      appearance of marked sclerotic thickening of the peritoneal membrane. We
      experienced a case with SEP accompanied by regional changes of peritoneum. A 37
      year-old woman with end-stage renal failure was started on continuous ambulatory
      peritoneal dialysis in 1985 and was transferred to hemodialysis in 1997. She was
      admitted because of ileus in 1998 with SEP and died of septicemia. The diagnosis
      of SEP was confirmed via the autopsy. The root of the mesentery was retracted and
      shortened. Since the peritoneal change was marked in the regions with free margin
      of mesentery and was less apparent in the regions not adhered to mesentery, it is
      indicated that mechanical stress also contributes to the occurrence of SEP. Since
      calcification and ossification were only seen in a free margin of small bowel
      from mesentery, it is suggested that there is a close relationship between
      calcification and ossification. Since fibrosis invaded into the muscle layer,
      dysfunction of bowel movement as well as bowel obstruction contributed to the
      appearance of ileus. It is suggested that mechanical stress by the root of
      mesentery which is retracted and shortened also contributes to the appearance of
      SEP.

PMID- 12218338
TI  - A Down syndrome patient treated by peritoneal dialysis.
AB  - Down syndrome patients are apparently not suited for peritoneal dialysis because
      of lacking cooperation. We report on an adult Down syndrome patient living in a
      difficult social environment suffering from ESRD due to posterior urethral valve.
      Comorbid conditions include decreased left ventricular function, hepatitis B
      carrier stage and hypothyroidism. The committed mother of the patient treats the
      patient successfully by peritoneal dialysis for a period of two years without
      episode of peritonitis.

PMID- 12218339
TI  - Is the bioreactivity of vitamin-E-modified dialyzer an expression of increased
      plasmatic vitamin E concentration?
AB  - The present study was designed to test the biocompatibility of a new vitamin E
      modified multilayer membrane compared with highly biocompatible polysulphone
      dialyzer and acrylonitrile dialyzer. Thirty patients (mean age 53.2 +/- 15.3 SD
      years; dialytic age 36 +/- 5.6 months) were selected for the study. The study was
      divided into three periods of 6 months (phases A, B and C). In the first phase
      (from Jan. 1999 to June 1999) patients undergoing maintenance bicarbonate
      dialysis were randomly divided into three filter groups composed, respectively,
      of 10 patients: acrylonitrile group, polysulphone group and vitamin E-coated
      dialyzer group. In the phase B (from July 1999 to Dec. 1999) and in the phase C
      (from Jan. 2000 to June 2000), all three groups changed their own dialysis
      membranes. Vitamin E-coated dialyzer causes significant decreases in beta(2)
      microglobulin, ferritin and immunoglobulin G, a normalization of complement C3
      and an increase of plasmatic vitamin E compared to other filters. In the VE group
      homocysteine decreases but not in a significant manner. In addition, this
      dialyzer seems not to influence lipid pattern and protein-energy malnutrition
      parameters. These results clearly show a positive effect of this new filter in
      influencing different biochemical parameters, perhaps saving vitamin E and
      reducing polymorphonuclear cell activation.

PMID- 12218340
TI  - Late-onset cytomegalovirus-associated interstitial nephritis in a kidney
      transplant.
AB  - Cytomegalovirus is the most important viral infection in kidney transplants, but
      rarely affects the allograft after the sixth month posttransplantation. We
      present a patient who developed renal failure eighteen months posttransplant; a
      kidney biopsy showed cytomegalovirus inclusions, acute tubular necrosis and mild
      interstitial nephritis. After intravenous ganciclovir, renal function transiently
      improved. Cytomegalovirus pp65 antigen was weekly reported as negative. One month
      later another biopsy was performed due to renal failure. The findings were
      consistent with tubular atrophy and severe interstitial nephritis. No
      cytomegalovirus cellular inclusions were found on histology, including
      immunohistochemical and polymerase chain reaction studies; pp65 antigen studies
      were persistently negative. Despite an attempt to recover renal function with
      steroid therapy, the patient restarted hemodialysis 20 months
      posttransplantation. This report suggests that cytomegalovirus should be
      considered as a late cause of kidney failure even in the absence of infection
      related symptoms. The irreversible allograft damage can be caused despite the
      successful eradication of the virus with intravenous ganciclovir.

PMID- 12218341
TI  - Effect of parathyroidectomy on blood pressure in dialysis patients.

PMID- 12218342
TI  - Tumoral calcinosis inducing systemic inflammatory response in a hemodialysis
      patient.

PMID- 12218343
TI  - Treatment with sevelamer decreases bicarbonate levels in hemodialysis patients.

PMID- 12218344
TI  - Performance of the newer type (Lixelle Type S-15) on direct hemoperfusion beta-2
      microglobulin adsorption column for dialysis-related amyloidosis.

PMID- 12218345
TI  - Weight in the balance.
AB  - The adage 'we are what we eat' is taking on a new meaning in our well-fed and
      increasingly sedentary culture, as many of us convert much of our excess food
      into body fat; in the USA, 60% of the population is now considered to be
      overweight. Obesity brings with it an increased risk of developing type II
      diabetes, hypertension and heart disease, so the mechanisms that control food
      intake and body weight are of considerable importance for public health and
      clinical medicine. The mass of body fat is now known to be regulated by several
      hormones and neuropeptides. Two of these, the circulating peptide hormones leptin
      and ghrelin have actions that include reciprocal effects on appetite-regulating
      neurons in the hypothalamus. This article reviews data discussed at a recent
      meeting(1), where an overview of recent developments in research into leptin and
      ghrelin was presented. Topics covered are the roles of leptin and ghrelin in the
      regulation of food intake and energy production; the integration of food intake
      with other energy-regulated processes, such as growth, sexual maturation and
      reproduction, sleep and the immune response; and pathological conditions, ranging
      from diabetes to psychiatric disorders.1 This report summarizes conclusions of
      the meeting 'Brain Somatic Cross-Talk and the Central Metabolism' held in Paris
      on January 28, 2002.

PMID- 12218346
TI  - Increased angiotensin II AT(1) receptor expression in paraventricular nucleus and
      hypothalamic-pituitary-adrenal axis stimulation in AT(2) receptor gene disrupted
      mice.
AB  - Angiotensin II AT(2) receptor gene-disrupted mice have increased blood pressure
      and response to angiotensin II, behavioral alterations, greater response to
      stress, and increased adrenal AT(1) receptors. We studied hypothalamic AT(1)
      receptor binding and mRNA by receptor autoradiography and in situ hybridization,
      adrenal catecholamines by HPLC, adrenal tyrosine hydroxylase mRNA by in situ
      hybridization and pituitary and adrenal hormones by RIA in AT(2) receptor-gene
      disrupted mice and wild-type controls. To confirm the role of adrenal AT(1)
      receptors, we treated wild-type C57 BL/6J mice with the AT(1) antagonist
      candesartan for 2 weeks, and measured adrenal hormones, catecholamines and
      tyrosine hydroxylase mRNA. In the absence of AT(2) receptor transcription, we
      found increased AT(1) receptor binding in brain areas involved in the regulation
      of the hypothalamic-pituitary-adrenal axis, the hypothalamic paraventricular
      nucleus and the median eminence, and increased adrenal catecholamine synthesis as
      shown by higher adrenomedullary tyrosine hydroxylase mRNA and higher adrenal
      dopamine, norepinephrine and epinephrine levels when compared to wild-type mice.
      In addition, in AT(2) receptor gene-disrupted mice there were higher plasma
      adrenocorticotropin (ACTH) and corticosterone levels and lower adrenal
      aldosterone content when compared to wild-type controls. Conversely, AT(1)
      receptor inhibition in CB57 BL/6J mice reduced adrenal tyrosine hydroxylase mRNA
      and catecholamine content and increased adrenal aldosterone content. These
      results can help to explain the enhanced response of AT(2) receptor gene
      disrupted mice to exogenous angiotensin II, support the hypothesis of cross-talk
      between AT(1) and AT(2) receptors, indicate that the activity of the hypothalamic
      pituitary-adrenal axis parallels the AT(1) receptor expression, and suggest that
      expression of AT(1) receptors can be dependent on AT(2) receptor expression. Our
      results provide an explanation for the increased sensitivity to stress in this
      model.

PMID- 12218347
TI  - Chronic hypercortisolemia inhibits dopamine synthesis and turnover in the nucleus
      accumbens: an in vivo microdialysis study.
AB  - Over 60% of patients with Cushing's syndrome suffer from major depression, which
      frequently abates after correction of the hypercortisolism. The mesolimbic and
      mesocortical dopaminergic (DAergic) systems are thought to participate in
      psychiatric disorders. In this study, we investigated whether hypercortisolemia
      affects indices of DAergic activity in the nucleus accumbens (NAc) and the
      prefrontal cortex (PFC) of freely moving rats. Cortisol (CORT, 25 mg/kg/day) was
      infused subcutaneously for 7 days via an osmotic minipump. Microdialysate
      collection (30-min periods, 2 microl/min) began 24 h after probe placement.
      Concentrations of dihydroxyphenylalanine (DOPA) in interstitial fluid in the
      nucleus accumbens (NAc) and perifrontal cortex (PFC) were measured before and
      after local perfusion with NSD-1015, an irreversible inhibitor of L-aromatic
      amino acid decarboxylase, to assess local dopamine (DA) biosynthesis. The sum of
      microdialysate DA, dihydroxyphenylacetic acid, and homovanillic acid was used as
      an index of local DA turnover. DOPA accumulation after NSD-1015 was markedly
      attenuated in CORT-treated compared with saline-treated animals (5,703 +/- 1,849
      vs. 10,902 +/- 2,454 pg/ml; p < 0.01). In contrast, the two groups did not differ
      in DOPA accumulation in the PFC. Values for the turnover index of DA were also
      significantly lower in CORT-treated animals in the NAc but not in the PFC. The
      results indicate that CORT inhibits DA synthesis and turnover in the NAc but not
      in the PFC. Region-specific CORT-induced inhibition of DAergic activity may help
      to explain depressive symptoms in patients with chronic hypercortisolemia and
      normalization after medical or surgical correction of hypercortisolism.

PMID- 12218348
TI  - Enhanced glucocorticoid feedback inhibition of hypothalamo-pituitary-adrenal
      responses to stress in adult rats neonatally treated with dexamethasone.
AB  - We studied the long-term effect of neonatal treatment with the synthetic
      glucocorticoid dexamethasone (DEX) on stress responsivity later in life. It was
      found that the plasma adrenocorticotropin hormone (ACTH) and corticosterone
      (CORT) responses induced by novelty or conditioned fear stress were markedly
      attenuated in adult rats that had been neonatally treated with DEX as compared
      with saline (SAL)-treated controls. Since there were no differences in the heart
      rate, body temperature, plasma noradrenaline, plasma adrenaline and behavioral
      responses to these stressors, this points to a deficit within the hypothalamic
      pituitary-adrenal (HPA) axis of DEX rats. We found no differences between DEX and
      SAL rats in basal plasma CORT concentrations measured throughout the circadian
      cycle, nor in the fraction unbound of CORT circulating under resting conditions,
      indicating normal tonic regulation of the HPA axis in DEX rats. Since we also
      found no differences in the hormonal responses induced by intravenous injection
      of graded doses of ACTH or corticotropin-releasing hormone (CRH), we investigated
      the sensitivity of the HPA response to stress for inhibition by glucocorticoids.
      Pretreatment with a low dose of CORT that did not affect the HPA response of SAL
      rats markedly inhibited the ACTH and CORT responses induced by novelty stress in
      DEX rats. This strongly suggests that an enhanced corticosteroid feedback
      underlies the blunted HPA response to stress in DEX rats. Finally, using
      quantitative immunocytochemistry, we found an increase in arginine-vasopressin
      (AVP) but not CRH stores in the external zone of the median eminence, suggesting
      an altered AVP/CRH ratio in the secretory output of the hypophysiotropic
      paraventricular nucleus. Taken together, our results show that exposure to DEX
      during early life leads to hyporesponsivity of the HPA axis to stress most likely
      due to hypersensitivity of the axis for negative feedback by corticosteroids at
      the suprapituitary level.

PMID- 12218349
TI  - An autocrine role for pituitary GABA: activation of GABA-B receptors and
      regulation of growth hormone levels.
AB  - There is increasing evidence suggesting that the neurotransmitter gamma
      aminobutyric acid (GABA) is a local factor involved in the regulation of
      endocrine organs. Examples of such functions are documented in the pancreas, but
      recent results suggest that GABA may act in a similar way in the pituitary, in
      which GABA receptors are expressed and pituitary growth hormone (GH) cells
      provide a source of GABA. We hypothesised that GABA secreted in somatotropes may
      act as an autoregulatory signaling molecule. To test this hypothesis we first
      examined the nature of GABA receptors expressed by GH cells. RT-PCR analysis
      demonstrated that GABA-B receptor subunits R1 and R2 are present in the whole rat
      pituitary. Laser microdissection of immunostained GH cells, followed by RT-PCR as
      well as immunoelectron microscopy, showed that GABA-B receptors are expressed on
      somatotropes. To investigate GABA-B receptor function in somatotropes, we used
      rat GH3 adenoma cells, which, like pituitary GH cells, express GABA-B R1 and R2
      (as assessed by RT-PCR and immunoelectron microscopy) and produce GABA (checked
      by high performance liquid chromatography). After inhibition of endogenous GABA
      synthesis, GH production was stimulated by baclofen, a chromatography). After
      inhibition of endogenous GABA synthesis, GH production was stimulated by
      baclofen, a GABA-B receptor agonist. By contrast, blocking GABA-B receptors by an
      antagonist, phaclofen, decreased GH levels. We conclude that in GH-producing
      cells, GABA acts as an autocrine factor via GABA-B receptors to control GH
      levels.

PMID- 12218350
TI  - Splenic denervation blocks leptin-induced enhancement of humoral immunity in
      Siberian hamsters (Phodopus sungorus).
AB  - Nontropical rodents have evolved adaptations to maximize winter survival,
      including alterations in reproduction, energy balance and immunity. Short-day
      housed Siberian hamsters display reductions in body fat and decreases in humoral
      immunity compared with long-day hamsters. The hormone leptin, secreted by adipose
      tissue, varies in response to changes in body fat and has been implicated in
      photoperiodic changes in immunity. In addition, the metabolic effects of this
      hormone appear to be mediated by the sympathetic nervous system (SNS). Very
      little is known, however, regarding the role of the SNS in regulating the effects
      of leptin on immunity. The goal of the present study was to examine the effects
      of splenic denervation on leptin-induced immune enhancement of short-day Siberian
      hamsters. Male hamsters were housed in long (LD 16:8) or short days (LD 8:16) for
      10 weeks. Half of the animals in each photoperiod received surgical denervations
      of the spleen; the remaining animals received sham operations. In addition,
      animals in each group were implanted with osmotic minipumps containing either
      leptin or vehicle. Hamsters were then injected with keyhole limpet hemocyanin
      (KLH) and serum anti-KLH antibody production was assessed. Short-day hamsters
      displayed decreased humoral immunity in short versus long days; leptin attenuated
      the short-day decrease but did not enhance immunity of long-day hamsters.
      Furthermore, splenic denervation blocked the leptin-induced increase in immunity
      in short-day hamsters. Collectively, these data suggest that leptin plays an
      important role in regulating seasonal changes in humoral immunity of Siberian
      hamsters and the effects of leptin occur, at least in part, via changes in the
      SNS innervation of lymphoid tissue.

PMID- 12218351
TI  - Maternal adrenalectomy abrogates the effect of fetal alcohol exposure on the
      interleukin-1beta-induced febrile response: gender differences.
AB  - Fetal alcohol exposure (FAE) has been shown to blunt the febrile component of the
      primary host-defense response to infection induced experimentally by systemic
      administration of interleukin (IL)-1beta. Given that maternal adrenalectomy (ADX)
      can prevent various postnatal effects of FAE, the present experiments were
      designed to determine whether maternal ADX would prevent the blunted IL-1beta
      induced febrile response of fetal alcohol-exposed offspring and whether the
      effects of maternal ADX would be gender related. Timed-pregnant rats underwent
      ADX or were sham-operated on gestation day (GD) 7, or remained intact (without
      any surgery), and were fed ethanol-containing (E) or pair-fed (PF) liquid diets
      or normal (N) rat chow and water from GD 8 to GD 21. As adults, male and female
      E, PF and N offspring were injected with saline on day 1 and with IL-1beta (2
      microg/kg, i.p.) on day 2 at 09.00 h and the body temperature was recorded
      biotelemetrically for 8.5 h. IL-1beta produced significantly lower febrile
      responses in female than in male offspring of intact dams, irrespective of
      prenatal diet. Furthermore, prenatal surgical stress differentially affected the
      IL-1beta-induced febrile response of male and female normally fed offspring.
      Additionally, in both male and female offspring of intact dams, FAE significantly
      attenuated the IL-1beta-induced febrile response. In males, FAE also attenuated
      the febrile response in the offspring of maternal sham-operated dams, and this
      effect was completely reversed by maternal ADX. In females, both maternal sham
      surgery and ADX reversed the effect of FAE on the febrile response. These
      findings suggest that maternal adrenal mediators are essential for the long-term
      effect of FAE on the febrile response in male offspring. In females, early
      prenatal surgical stress is sufficient to reverse the effects of FAE, possibly
      via adrenal-independent mechanisms that affect the thermoregulatory system.

PMID- 12218352
TI  - Gene expression profiling of human diseases by serial analysis of gene
      expression.
AB  - Until recently, the approach to understanding the molecular basis of complex
      syndromes such as cancer, coronary artery disease, and diabetes was to study the
      behavior of individual genes. However, it is generally recognized that expression
      of a number of genes is coordinated both spatially and temporally and that this
      coordination changes during the development and progression of diseases. Newly
      developed functional genomic approaches, such as serial analysis of gene
      expression (SAGE) and DNA microarrays have enabled researchers to determine the
      expression pattern of thousands of genes simultaneously. One attractive feature
      of SAGE compared to microarrays is its ability to quantify gene expression
      without prior sequence information or information about genes that are thought to
      be expressed. SAGE has been successfully applied to the gene expression profiling
      of a number of human diseases. In this review, we will first discuss SAGE
      technique and contrast it to microarray. We will then highlight new biological
      insights that have emerged from its application to the study of human diseases.

PMID- 12218353
TI  - Protection by tetramethylpyrazine in acute absolute ethanol-induced gastric
      lesions.
AB  - Acute oral administration of absolute ethanol (1.0 ml/kg) to fasting rats
      produced extensive necrosis of the gastric mucosa within 1 h. Pretreatment 30 min
      before administration of ethanol with oral tetramethylpyrazine (TMP) prevented
      this necrosis. Gross examination of the gastric mucosa of rats that received TMP
      showed fewer gastric lesions than that of rats who did not receive TMP. TMP
      pretreatment in rats exhibited superoxide scavenging activity in absolute ethanol
      induced lipid peroxidation in gastric mucosal homogenates. TMP added in vitro to
      gastric homogenates made from control rats also showed scavenging activity. We
      conclude that the gastric protective mechanism of TMP could be attributed, at
      least in part, to its ability to inhibit lipid peroxidation and hence indirectly
      protect the gastric mucosa from oxidative stress.

PMID- 12218354
TI  - Hepatoprotective effects of Arctium lappa Linne on liver injuries induced by
      chronic ethanol consumption and potentiated by carbon tetrachloride.
AB  - Arctium lappa Linne (burdock) is a perennial herb which is popularly cultivated
      as a vegetable. In order to evaluate its hepatoprotective effects, a group of
      rats (n = 10) was fed a liquid ethanol diet (4 g of absolute ethanol/ 80 ml of
      liquid basal diet) for 28 days and another group (n = 10) received a single
      intraperitoneal injection of 0.5 ml/kg carbon tetrachloride (CCl(4)) in order to
      potentiate the liver damage on the 21st day (1 day before the beginning of A.
      lappa treatment). Control group rats were given a liquid basal diet which did not
      contain absolute ethanol. When 300 mg/kg A. lappa was administered orally 3 times
      per day in both the 1-day and 7-day treatment groups, some biochemical and
      histopathological parameters were significantly altered, both in the ethanol
      group and the groups receiving ethanol supplemented with CCl(4). A. lappa
      significantly improved various pathological and biochemical parameters which were
      worsened by ethanol plus CCl(4)-induced liver damage, such as the ethanol plus
      CCl(4)-induced decreases in total cytochrome P-450 content and NADPH-cytochrome c
      reductase activity, increases in serum triglyceride levels and lipid peroxidation
      (the deleterious peroxidative and toxic malondialdehyde metabolite may be
      produced in quantity) and elevation of serum transaminase levels. It could even
      restore the glutathione content and affect the histopathological lesions. These
      results tended to imply that the hepatotoxicity induced by ethanol and
      potentiated by CCl(4) could be alleviated with 1 and 7 days of A. lappa
      treatment. The hepatoprotective mechanism of A. lappa could be attributed, at
      least in part, to its antioxidative activity, which decreases the oxidative
      stress of hepatocytes, or to other unknown protective mechanism(s).

PMID- 12218355
TI  - Tetramethylpyrazine protects mice against thioacetamide-induced acute
      hepatotoxicity.
AB  - In this study, the intraperitoneal administration of 1 mg/kg thioacetamide (TAA)
      produced hepatotoxicity in mice. The increase in serum SGOT and SGPT produced at
      24 h by this regimen was decreased in a dose-dependent manner by coadministration
      of tetramethylpyrazine (TMP; 10, 25 and 50 mg/kg). A rise in serum interleukin-2
      was similarly prevented. Increased concentrations of malondialdehyde (MDA)
      generated in vitro in liver homogenates prepared from TAA-treated mice were
      decreased by TMP treatments. The increase in MDA produced by TAA was also
      prevented by in vitro addition of TMP to liver homogenates. These results suggest
      that part of the hepatocellular injury induced by TAA is mediated by oxidative
      stress caused by the action of cytokines through lipid peroxidation. TMP appears
      to act by preventing lipid peroxidation.

PMID- 12218356
TI  - Involvement of tachykinin NK(1) and NK(2) receptors in changes in lung mechanics
      and airway microvascular leakage during the early phase of endotoxemia in Guinea
      pigs.
AB  - We investigated the role of tachykinins in airway neurogenic responses occurring
      in the early phase of endotoxemia. Forty-eight anesthetized guinea pigs were
      evenly divided into six groups pretreated with either saline vehicle, CP-96,345
      (a tachykinin NK(1) receptor antagonist), SR-48,968 (a tachykinin NK(2) receptor
      antagonist) or CP-96,345 and SR-48,968 in combination. Animals then received an
      intravenous injection of either saline (the vehicle for endotoxin) or endotoxin
      (30 mg/kg). Total lung resistance (R(L)) and dynamic lung compliance (C(dyn))
      were continuously measured before and 30 min after administration of saline or
      endotoxin. Airway microvascular leakage was assessed at the end of the
      observation period. Endotoxin significantly increased R(L) and decreased C(dyn)
      10 min after intravenous endotoxin injection. Plasma extravasation significantly
      increased in the trachea, main bronchi and intrapulmonary airways with endotoxin
      administration. These changes in lung mechanics were abolished by SR-48,968, but
      were unaffected by CP-96,345. The plasma extravasation was largely attenuated by
      CP-96,345 and/or SR-48,968. We conclude that (1) endogenous tachykinins play an
      important role in producing changes in lung mechanics and airway microvascular
      leakage during the early phase of endotoxemia and (2) activation of tachykinin
      NK(2) receptors is responsible for the former response, while activation of both
      tachykinin NK(1) and NK(2) receptors is involved in the latter response.

PMID- 12218358
TI  - Perception of unsteadiness in patients with dizziness: association with handicap
      and imbalance.
AB  - Dizziness is a common problem in patients seeking medical help and is often
      associated with imbalance and handicap. This study aimed to reveal whether the
      perception of unsteadiness could be an indication of greater imbalance and
      handicap in these patients. Patients with dizziness were categorized into two
      groups, steady patients (n = 15) and unsteady patients (n = 23), based on the
      presence or absence of self-perceived unsteadiness. The level of self-perceived
      handicap was evaluated by the Dizziness Handicap Inventory. Static balance
      ability was evaluated using a force platform and the center of pressure motion
      was calculated during various quiet standing conditions. Dynamic balance ability
      was evaluated by the functional forward reach test and Dynamic Gait Index. All
      the patients also went through isometric strength tests of the lower extremities.
      It was found that all patients reported themselves to be handicapped by
      dizziness. Patients who perceived themselves to be unsteady had greater handicap
      and poorer static standing, but did not differ from the steady patients in regard
      to muscle strength or functional balance tests. Thus, self- perceived
      unsteadiness was associated with greater handicap and poorer static balance in
      dizzy patients. In clinical management of these patients, special attention
      should be paid to balance and handicap.

PMID- 12218357
TI  - A modified technique for tail cuff pressure measurement in unrestrained conscious
      rats.
AB  - In physiological experiments, it is essential to measure arterial pressure (AP)
      and heart rate (HR) in animals. Tail cuff pressure (TCP) measurement using
      photoelectric volume oscillometry has been commonly used. We designed a new
      technique for continuous measurement of AP and HR in conscious, unrestrained
      rats. This is based on the observation that fixation of the rat's tail with tape
      keeps the animal in position without struggling. The animal is free to move its
      body. To test the accuracy of this new technique, Sprague-Dawley rats underwent
      four AP and HR measurement techniques. These included a new unrestrained method
      (UR), which was compared to the following three methods: traditional restrained
      TCP method with restrainer, direct monitoring of AP and HR with femoral artery
      catheterization and a combination of photoelectric volume oscillometry (with body
      heating to 37 degrees C) and femoral arterial recording. The results show that
      the modified UR measurement provides accurate data on AP and HR. This method
      obtains a lower value of HR and similar mean AP when compared to direct
      monitoring from femoral arterial catheterization. Accordingly, the modified
      unrestrained TCP measurement can be used in conscious rats as a noninvasive
      method.

PMID- 12218359
TI  - Purine, kynurenine, neopterin and lipid peroxidation levels in inflammatory bowel
      disease.
AB  - The kynurenine metabolites of tryptophan may be involved in the regulation of
      neuronal activity and thus gut motility and secretion. We have now performed a
      pilot study to measure serum concentrations of purines and kynurenines in
      patients with mild inflammatory bowel disease, as well as in sex- and age-matched
      control subjects. For some analyses, the patients were subdivided into subgroups
      of those with Crohn's disease and those with ulcerative colitis. The analyses
      indicated an increased activity in one branch of the kynurenine pathway. While
      there was no demonstrable difference in neopterin levels in either of the patient
      groups compared with controls, indicating that the disorders were in an inactive
      quiescent phase, both groups showed significantly higher levels of lipid
      peroxidation products. This suggests the presence of increased oxidative stress
      even during relative disease inactivity. The increased level of kynurenic acid
      may represent either a compensatory response to elevated activation of enteric
      neurones or a primary abnormality which induces a compensatory increase in gut
      activity. In either case, the data may indicate a role for kynurenine modulation
      of glutamate receptors in the symptoms of inflammatory bowel disease.

PMID- 12218360
TI  - Cardiac glycosides induce resistance to tubulin-dependent anticancer drugs in
      androgen-independent human prostate cancer.
AB  - Due to high prevalence and mortality and the lack of effective therapies,
      prostate cancer is one of the most crucial health problems in men. Drug
      resistance aggravates the situation, not only in human prostate cancer but also
      in other cancers. In this study, we report for the first time that cardiac
      glycosides (e.g. ouabain and digitoxin) induced resistance of human prostate
      cancer cells (PC-3) in vitro to tubulin-binding anticancer drugs, such as
      paclitaxel, colchicine, vincristine and vinblastine. Cardiac glycosides exhibited
      amazing ability to reverse the G2/M arrest of the cell cycle and cell apoptosis
      induced by tubulin-binding agents. However, neither ionomycin (a Ca(2+)
      ionophore) nor veratridine (a Na(+) ionophore) mimicked the preventive action of
      cardiac glycosides, indicating that elevation of the intracellular Ca(2+)
      concentration and Na(+) accumulation were not involved in the cardiac glycoside
      action. Furthermore, cardiac glycosides showed little influence on the effects
      induced by actinomycin D, anisomycin and doxorubicin, suggesting selectivity for
      microtubule-targeted anticancer drugs. Using in situ immunofluorescent detection
      of mitotic spindles, our data showed that cardiac glycosides diminished
      paclitaxel-induced accumulation of microtubule spindles; however, in a non-cell
      assay system, cardiac glycosides had little influence on colchicine- and
      paclitaxel-induced microtubule dynamics. Using an isotope-labeled assay method,
      we found that ouabain modestly but significantly inhibited the transport of
      [(14)C]paclitaxel from the cytosol into the nucleus. It is suggested that cardiac
      glycosides inhibit the G2/M arrest induced by tubulin-binding anticancer drugs
      via an indirect blockade on microtubule function. The decline in transport of
      these drugs into the nucleus may partly explain the action of cardiac glycosides.

PMID- 12218361
TI  - Inhibition of arachidonate metabolism in human epidermoid carcinoma a431 cells
      overexpressing phospholipid hydroperoxide glutathione peroxidase.
AB  - Phospholipid hydroperoxide glutathione peroxidase (PHGPx), a selenium-dependent
      glutathione peroxidase, can interact with lipophilic substrates, including
      phospholipid hydroperoxides, fatty acid hydroperoxides and cholesterol
      hydroperoxides, and can reduce them to hydroxide compounds. It also seems to be a
      major regulator of lipid oxygenation in human epidermoid carcinoma A431 cells. In
      order to study the functional role of PHGPx in the regulation of 12-lipoxygenase
      and cyclooxygenase, cDNA of PHGPx was inserted into pcDNA3.1/His, and a plasmid
      designated as S4 with the His-tag sequence inserted between PHGPx and its 3'
      untranslated region was constructed. A number of stable transfectants of A431
      cells that could express the tag-PHGPx were generated using plasmid S4. Using an
      intact cell assay system, the metabolism of arachidonic acid to prostaglandin
      E(2) significantly decreased in stable transfectants of overexpressing PHGPx
      compared to that in a vector control cell line. If the intact cell assay was
      carried out in the presence of 13-hydroperoxyoctadecadienoic acid as a stimulator
      of lipid peroxidation, formation of 12-hydroxyeicosatetraenoic acid from
      arachidonic acid also significantly decreased in stable transfectants of
      overexpressing PHGPx compared to that in a vector control cell line, indicating
      that PHGPx could downregulate the 12-lipoxygenase activity in cells. These
      results support the hypothesis that PHGPx plays a pivotal role in the regulation
      of arachidonate metabolism in A431 cells.

PMID- 12218362
TI  - Identification of additional IE2-p86-responsive cis-repressive sequences within
      the human cytomegalovirus major immediate early gene promoter.
AB  - Human cytomegalovirus (HCMV) is a ubiquitous human pathogen that is the leading
      viral cause of birth defects and also causes significant morbidity and mortality
      in immunosuppressed individuals. The immediate early (IE) genes, IE1-p72 and IE2
      p86, are the first HCMV genes expressed after infection under the control of a
      strong transcriptional enhancer-promoter, the major IE promoter (MIEP). Gene
      expression mediated by the predominant IE2-p86 is believed to be essential for
      the progression of viral production, as well as for the development of HCMV
      associated pathogenesis. To gain further understanding of the transcriptional
      activity of IE2-p86, we attempted to isolate its downstream target genes within
      the HCMV genome. By a modified approach coupling the methods of cyclic
      amplification and selection of targets and selection and amplification of binding
      sites, several HCMV genomic fragments were identified based on their ability to
      bind to IE2-p86. Two additional IE2-p86-responsive elements other than the cis
      repressive sequence (CRS) were identified within the MIEP and were termed -240
      and -170 boxes. These two cis elements resemble the CRS in their sequences, as
      they contain the CG(N)(10)CG motif. The binding of IE2-p86 to these two distal
      CRS-like sequences was further confirmed by DNase I footprinting analysis and
      electrophoretic mobility shift assay. Promoter activity analysis in the transient
      expression system suggested that these two cis elements act functionally as IE2
      p86-responsive repressive sequences to cooperate with the CRS to suppress MIEP
      expression.

PMID- 12218363
TI  - Nonreceptor protein tyrosine and lipid phosphatases in type I fc(epsilon)
      receptor-mediated activation of mast cells and basophils.
AB  - Protein tyrosine and lipid phosphorylations are early and critical events in type
      1 Fc(epsilon) receptor (Fc(epsilon)RI)-mediated activation of mast cells and
      basophils. Tyrosine phosphorylation of Fc(epsilon)RI subunits as well as other
      signal transduction molecules reflects the balance between the action of protein
      tyrosine kinases and phosphatases. Similarly, the phosphate content of inositol
      phospholipids, involved in the recruitment of signalling molecules to the plasma
      membrane and the generation of secondary messengers, is the net result of the
      opposing effects of phosphoinositide kinases and lipid phosphatases. This review
      summarizes the current understanding of the structural and functional aspects of
      nonreceptor protein tyrosine phosphatases (SHP-1, SHP-2, HePTP, PTP20, PRL1,
      PRL2, PTP-MEG1 and PTP-MEG2) and lipid phosphatases (SHIP and SHIP2) in the
      activation of mast cells and basophils after Fc(epsilon)RI aggregation. New
      approaches towards a deeper understanding of the role of phosphatases in mast
      cell physiology are also discussed.

PMID- 12218364
TI  - Expression systems for production of recombinant allergens.
AB  - Recombinant allergenic proteins have been produced in a variety of different
      expression systems. This review gives examples of and compares prokaryotic
      expression systems, such as Escherichia coli, and eukaryotic systems including
      the yeasts, Saccharomyces cerevisiae and Pichia pastoris, baculovirus-insect cell
      systems, mammalian cell systems and plant systems. Important factors to consider
      in choosing an expression system are discussed and examples of applications are
      given.

PMID- 12218365
TI  - Allergies to cross-reactive plant proteins. Latex-fruit syndrome is comparable
      with pollen-food allergy syndrome.
AB  - Both latex-fruit syndrome and oral allergy syndrome concomitant with pollinosis
      (pollen-food allergy syndrome) are considered to be caused by cross-reactivity
      between sensitizers and symptom elicitors. The cross-reactive food allergens
      relevant to these syndromes are mostly sensitive to heat and digestive enzymes.
      Such a vulnerable antigen cannot sensitize people perorally but provokes allergic
      reactions in already sensitized patients based on its cross-reactivity to the
      corresponding sensitizer. These types of food allergens are often called
      incomplete food allergens or nonsensitizing elicitors. Their features contrast
      with those of complete food allergens that have the capacity for peroral
      sensitization as well as symptom elicitation. Although highly antigenic and cross
      reactive, carbohydrate epitopes do not generally elicit allergic reactions and
      often disturb in vitro IgE tests. Recent research has revealed that some of the
      cross-reactive allergens responsible for the two syndromes are proteins related
      to the defense responses of higher plants. Plant defense-related proteins are
      relatively conserved in the course of evolution and can supply cross-reactive
      epitopes. It is important to note that various stresses can stimulate the
      expression of these proteins, which implies that allergens increase in plants
      under stressful conditions like severe growing situations and exposure to some
      kinds of chemicals. Because defense-related proteins usually provide a plant with
      resistance to stresses, varieties that are apt to intensively induce such
      proteins are agriculturally valuable. Less toxic substances that cause crops to
      express defensive proteins are being investigated as a new type of agrochemical.
      Moreover, some defense-related proteins are going to be constantly produced in
      genetically modified plants. Even though these proteins can be useful
      agriculturally, their allergenicity should be evaluated carefully.

PMID- 12218366
TI  - Bioinformatic methods for allergenicity assessment using a comprehensive allergen
      database.
AB  - BACKGROUND: A principal aim of the safety assessment of genetically modified
      crops is to prevent the introduction of known or clinically cross-reactive
      allergens. Current bioinformatic tools and a database of allergens and gliadins
      were tested for the ability to identify potential allergens by analyzing 6
      Bacillus thuringiensis insecticidal proteins, 3 common non-allergenic food
      proteins and 50 randomly selected corn (Zea mays) proteins. METHODS: Protein
      sequences were compared to allergens using the FASTA algorithm and by searching
      for matches of 6, 7 or 8 contiguous identical amino acids. RESULTS: No
      significant sequence similarities or matches of 8 contiguous amino acids were
      found with the B. thuringiensis or food proteins. Surprisingly, 41 of 50 corn
      proteins matched at least one allergen with 6 contiguous identical amino acids.
      Only 7 of 50 corn proteins matched an allergen with 8 contiguous identical amino
      acids. When assessed for overall structural similarity to allergens, these 7 plus
      2 additional corn proteins shared >or=35% identity in an overlap of >or=80 amino
      acids, but only 6 of the 7 were similar across the length of the protein, or
      shared >50% identity to an allergen. CONCLUSIONS: An evaluation of a protein by
      the FASTA algorithm is the most predictive of a clinically relevant cross
      reactive allergen. An additional search for matches of 8 amino acids may provide
      an added margin of safety when assessing the potential allergenicity of a
      protein, but a search with a 6-amino-acid window produces many random, irrelevant
      matches.

PMID- 12218367
TI  - Immunological and structural analysis of IgE-mediated cross-reactivity between
      manganese superoxide dismutases.
AB  - BACKGROUND: Allergy results from inappropriate immune responses to normally
      innocuous proteins. More than 300 IgE-binding proteins have been cloned and shown
      to cover structurally and functionally heterogeneous protein families including
      enzymes, backbone and storage proteins as well as proteins with unknown function.
      Structurally related cross-reactive allergens are involved in the pathogenesis of
      important clinical syndromes. We found that phylogenetically highly conserved
      proteins, including human manganese superoxide dismutase (MnSOD), are involved in
      IgE-mediated autoreactivity. METHODS: MnSOD cloned from different
      phylogenetically distant species were produced as recombinant proteins in
      Escherichia coli and used to study IgE-mediated cross-reactivity and
      proliferative responses in peripheral blood mononuclear cells (PBMC) of
      individuals sensitised to Aspergillus fumigatus MnSOD. Homology models of the
      three-dimensional structures of MnSOD from A. fumigatus, Drosophila melanogaster
      and Saccharomyces cerevisiae using the human MnSOD structure refined at 2.2 A as
      template were constructed to identify conserved amino acid residues exposed to
      the solvent. RESULTS: Cross-reactivity between the MnSOD at B and T cell level
      was demonstrated by inhibition experiments showing shared B cell epitopes and by
      the capability of the different MnSODs to induce proliferative responses in PBMCs
      of sensitised individuals. Structural modelling allowed to identify conserved
      residues exposed to the solvent. The identified residues are scattered over the
      sequence of the enzyme indicating putative conformational IgE-binding epitopes.
      CONCLUSIONS: The results obtained corroborate molecular mimicry as a plausible
      mechanism to explain autoreactivity to human MnSOD. Moreover, homology modelling
      provides a rational tool to identify conserved residues involved in defining
      cross-reactive B cell epitopes.

PMID- 12218369
TI  - Pine processionary caterpillar allergenicity increases during larval development.
AB  - BACKGROUND: In European countries, pine processionary caterpillar (Thaumetopoea
      pityocampa) is one of the species of Lepidoptera able to affect humans. Its
      allergenicity has been demonstrated in previous studies. However, in all of them
      larval extract in the fifth stage of development has been used as antigen.
      Therefore, allergenicity of other larval stages was unknown. The objective of our
      study was to detect allergenic changes of pine processionary caterpillar during
      larval development. METHODS: Pine processionary caterpillar extracts in all
      larval stages were analyzed by SDS-PAGE. Immunoblotting was performed using
      patient sera with suggestive history of allergy and a positive prick test.

PMID- 12218368
TI  - Identification and characterization of the allergenic proteins of Bahia grass
      (Paspalum notatum) pollen.
AB  - BACKGROUND: Pollen of Bahia grass (Paspalum notatum) represents a major cause of
      type I allergy in diverse geographical areas, particularly in the southeastern
      coastal plain area of the United States. The aqueous protein extract of Bahia
      grass pollen contains the allergenically active components that produce skin-test
      positive reactions in sensitive patients. OBJECTIVE: The emphasis of this study
      included the identification and characterization of the allergenic proteins
      present in the crude protein aqueous extract of Bahia grass pollen. METHODS: The
      crude extract of Bahia grass pollen, partially purified by isoelectric focusing
      and fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE), was electroblotted onto nitrocellulose membranes, probed with sera
      from patients skin test positive to Bahia grass and detected using anti-human IgE
      conjugated peroxidase. RESULTS: Four allergenic proteins of Bahia grass pollen
      with estimated molecular weights of 45, 33, 31 and 28 kD were identified and
      characterized. Following treatments with deglycosylation enzymes, the 4 allergens
      retained their antigenic reactivity with Bahia-grass-allergic patient sera
      containing polyclonal IgE antibodies. CONCLUSION: The crude extract of Bahia
      grass pollen contains many proteins but only 4 have allergenic reactivity.
      Following deglycosylation treatment, Bahia grass allergenic proteins have
      retained their antigenic reactivity with Bahia-grass-allergic patient sera
      containing polyclonal IgE antibodies. Four proteins reactive with IgE were
      detected, but the 33-kD protein (pI of 6.59) was the most reactive.

PMID- 12218370
TI  - Monoclonal antibodies against the C(epsilon)mX domain of human membrane-bound IgE
      and their potential use for targeting IgE-expressing B cells.
AB  - BACKGROUND: IgE mediates immediate-type hypersensitivity reactions responsible
      for various allergic symptoms. It is secreted by IgE-producing plasma cells,
      which differentiate from B cells expressing membrane-bound IgE (mIgE) on their
      surface. The epsilon-chain of human mIgE contains a membrane-anchoring peptide
      and an extra 52-amino-acid (a.a.)-long domain (referred to as C(epsilon)mX)
      between the membrane anchor and the CH4 domain. OBJECTIVE: The study was designed
      to evaluate the effects of C(epsilon)mX-specific monoclonal antibodies (mAbs) to
      target IgE-expressing B cells and decrease IgE production. METHODS: A
      C(epsilon)mX-containing IgG1.Fc fusion protein was produced in CHO cells and used
      to immunize mice; five hybridoma clones secreting C(epsilon)mX-specific mAbs were
      obtained. RESULTS: Characterization of the mAbs using ELISA, immunoprecipitation,
      and immunoblotting methods showed that they could bind to both native and
      denatured forms of C(epsilon)mX. The mAbs exhibited mutual inhibition of binding
      to mIgE. Epitope mapping using synthetic peptides revealed that all five mAbs
      recognize the same epitope, RADWPGPP, located near the C-terminus of
      C(epsilon)mX. Binding of one of the mAbs to mIgE on SKO-007 cells induced the
      cross-linking of mIgE molecules on the cell surface, resulting in their patching
      and capping. In vitro functional analysis revealed that mAbs are able to cause
      complement-mediated cytotoxicity on transfectants expressing the Fc portion of
      mIgE. CONCLUSION: We have prepared several human mIgE-specific mAbs. The
      potential of the mAbs on targeting mIgE+ B cells was demonstrated by CDC
      analysis.

PMID- 12218371
TI  - Different IgE reactivity profiles in birch pollen-sensitive patients from six
      European populations revealed by recombinant allergens: an imprint of local
      sensitization.
AB  - BACKGROUND: Sensitivity to birch pollen allergens is a common feature among
      European patients with seasonal pollen allergy. In this in vitro study, we
      examined the specific serum IgE binding profiles to individual birch pollen
      allergens in birch-sensitive patients from six European populations. METHODS: The
      study included 242 patients from Finland, Sweden, Austria, France, Switzerland
      and Italy. All suffered from seasonal rhinoconjunctivitis and/or asthma. Their
      sera were analyzed for specific IgE reactivity to individual birch pollen
      allergens (recombinant Bet v 1, Bet v 2 and Bet v 4) and natural birch pollen
      extract using Pharmacia CAP System and immunoblotting. RESULTS: Almost all
      Finnish, Swedish and Austrian sera contained IgE specific for Bet v 1 (>or=98%).
      Bet v 1-specific IgE antibodies were found in 90% of the French sera, and in 65
      and 62% of the sera from Switzerland and Italy, respectively. Few Finnish (2%)
      and Swedish (12%) patients had IgE to Bet v 2, while Bet v 2 reactivity was more
      common in the other populations (20-43%). Reactivity to Bet v 4 was rare in all
      populations (5-11%) except for the Italian patients, in whom 3 of 11 sera were
      positive (27%). The immunoblot results supported the specific IgE profiles
      obtained with Pharmacia CAP System showing a broader IgE reactivity profile in
      patients from central and southern Europe as compared to northern Europe.
      CONCLUSION: Component-resolved allergy diagnosis with recombinant allergens
      reveals that the IgE reactivity profiles to individual birch pollen allergens
      vary between European populations. This observation may be explained by
      sensitization to different allergen sources and will have an impact on allergen
      specific prevention and therapy strategies.

PMID- 12218372
TI  - Influence of natural exposure to pollens and domestic animals on airway
      responsiveness and inflammation in sensitized non-asthmatic subjects.
AB  - BACKGROUND: Atopy may be a risk factor in the development of asthma. Indoor
      allergens are considered to be more potent asthma inducers than outdoor ones such
      as pollens. Lower airway inflammation may be present in non-asthmatic subjects
      during natural exposure to relevant allergens and may eventually lead to the
      development of asthma. AIMS: To document seasonal variation in lower airway
      responsiveness and inflammation in sensitized non-asthmatic subjects, during
      natural exposure to allergens, and to determine whether it is more marked in
      those exposed to animals to which they are sensitized. METHODS: Twenty-two atopic
      subjects were seen during and out of the pollen season. All (but the controls)
      were sensitized to domestic animals, and to trees, grasses or ragweed. Eleven
      were not exposed to animals at home and 8 were exposed. They were compared with 3
      normal controls. A respiratory questionnaire was administered, allergy skin prick
      tests, spirometry, methacholine challenge, blood and induced sputum with
      differential cell counts were obtained during the pollen season for all subjects.
      These tests were repeated out of the pollen season. RESULTS: Throughout the
      study, none of the subjects had asthma symptoms. Mean PC(20) was significantly
      lower in subjects exposed to animals compared with unexposed subjects or
      controls, both during and out of the pollen season. In season, subjects exposed
      to animals had significantly higher sputum eosinophil numbers than unexposed or
      normal control subjects. CONCLUSIONS: Non-asthmatic atopic subjects show variable
      degrees of airway responsiveness and inflammation. However, subjects exposed to
      animals show higher airway eosinophilia, which may suggest they are at increased
      risk of developing airway hyperresponsiveness and asthma.

PMID- 12218373
TI  - Serum interleukin-6 reflects disease severity and osteoporosis in mastocytosis
      patients.
AB  - BACKGROUND: Systemic mastocytosis (SM) is a condition typically characterized by
      an increased number of mast cells in the bone marrow or in skin areas known as
      urticaria pigmentosa. Patients may present with flushing, itching,
      gastrointestinal symptoms, arrhythmias, headaches and osteoporosis. Some patients
      experience systemic symptoms indicative of SM in the absence of a positive bone
      marrow or skin biopsy, and are known as 'clinical mastocytosis', but are herein
      referred to as suspected of having systemic mastocytosis. Serum tryptase has been
      increasingly used as a biochemical marker of mastocytosis, but is not always
      elevated. OBJECTIVE: To investigate the association of serum levels of two key
      mast cell mediators, interleukin-6 (IL-6) and tryptase, to each other and with
      disease severity in patients with mastocytosis. METHODS: Patients responded to an
      announcement from the Systemic Mastocytosis Society (USA) and submitted frozen
      serum samples, but the precise diagnosis made by their own health providers was
      not known until after the assays were completed. There were 9 suspected systemic
      mastocytosis (SuSM), 3 cutaneous mastocytosis (CM), 11 indolent systemic
      mastocytosis (ISM), and 3 aggressive systemic mastocytosis (ASM). Five normal
      volunteers (3 females/2 males) also submitted samples, as did 33 cardiac patients
      without coronary artery disease. For 2 days prior to and during the collection
      period, mastocytosis patients were asked to abstain from any over-the-counter or
      food products containing biogenic amines, as well as drugs prescribed for this
      condition. Serum levels of IL-6 and tryptase were measured using established
      assays. RESULTS: Twenty-six patients (14 females/12 males) submitted serum
      samples. There were 9 cases of SuSM (6 females/3 males) in whom tryptase values
      were borderline normal; IL-6 values were slightly elevated with one being high.
      In 3 cases of CM (2 females/1 male), both tryptase and IL-6 were slightly
      elevated. In patients with ISM (5 females/6 males), only 6/11 had any tryptase
      elevated significantly as compared to 9/11 with elevated serum IL-6. Three
      patients with ASM had significant elevations of both IL-6 and tryptase. The most
      consistent finding was that of IL-6 elevations in 7/7 patients (3 females/4
      males) who reported symptoms of osteoporosis and/or bone pain (1 SuSM, 3 ISM, 3
      ASM) in the absence of any coexisting condition involving bone pathology.
      CONCLUSION: Serum IL-6 is elevated in mastocytosis patients and correlates with
      severity of symptoms and the presence of osteoporosis. High serum IL-6 may not
      only signify disease progression, but may also participate in the pathophysiology
      of mastocytosis.

PMID- 12218374
TI  - Enhancement of allergic skin responses by total sleep deprivation in patients
      with allergic rhinitis.

PMID- 12218375
TI  - Evaluation of adolescent statural growth in health and disease: reliability of
      assessment from height measurement series and development of an automated
      algorithm.
AB  - OBJECTIVES: The precise evaluation of adolescent growth spurt is necessary for
      numerous clinical research studies of growth disorders and treatments. The
      objectives of our study were: (1) to evaluate the reliability of clinicians'
      'manual' evaluation of the adolescent growth spurt from a collected series of
      height data, and (2) to construct an automated algorithm to determine the
      duration of the two phases of growth in health and disease (spurt and final slow
      growth) independent of clinical pubertal stages. METHODS: One hundred and seventy
      four growth curves of normally growing, GH-deficient and Turner's syndrome
      subjects were presented twice to 2 experienced clinicians. Disagreement between
      evaluations and clinicians were settled to obtain a 'consensual gold standard'
      evaluation versus which the algorithm was assessed. Kappa statistics and Bland
      Altman analyses were used to evaluate the reliability and agreement of the
      evaluations. RESULTS: The reliability of 'manual' evaluation of adolescent growth
      spurt from collected series of height data appeared to be poor. Conversely, the
      developed algorithm is perfectly reliable and satisfactorily valid. Discrepancies
      with the clinical consensual gold standard were always fewer than the
      discrepancies between the expert clinicians, and were observed in similarly
      difficult curves. CONCLUSION: The developed algorithm may be useful for diverse
      clinical and biological research applications in children with growth disorders.
      This study also confirms the value of a comprehensive investigation of growth
      during adolescence independent of clinical staging.

PMID- 12218376
TI  - Spontaneous nocturnal leptin secretion in children with myelomeningocele and
      growth hormone deficiency.
AB  - OBJECTIVE: To examine the spontaneous leptin secretion in patients with
      myelomeningocele (MMC) and growth hormone deficiency (GHD). METHODS: Serum leptin
      levels were studied in 10 prepubertal MMC patients with GHD (CA 6.2 +/- 0.5
      years), 10 patients with idiopathic GHD (IGHD; CA 7.6 +/- 0.7 years) and 12
      children with normal variant short stature (NVSS; CA 7.6 +/- 0.5 years). Mean BMI
      (kg/m(2)) values of the groups did not differ significantly. Nocturnal leptin
      levels were analyzed over 10 h (blood samples every 20 min) and measured by
      specific radioimmunoassay. RESULTS: Mean leptin concentrations did not correlate
      with BMI in MMC patients. Nocturnal leptin secretion of MMC patients was
      significantly different to those of children with IGHD and NVSS. Morning leptin
      levels did not decline as observed in both other groups. CONCLUSION: Since all
      groups were matched for BMI values, we suggest a hypothalamic dysregulation of
      leptin secretion in MMC patients.

PMID- 12218377
TI  - Lipoatrophic diabetes-associated utero-ovarian dysfunction: influence of cellular
      lipid deposition on norepinephrine indices.
AB  - OBJECTIVE: Elucidation of the intracellular lipoatrophic diabetic state and the
      concomitant alterations in norepinephrine (NE) parameters characterizing female
      reproductive failure. METHODS: Quantitation of intrinsic NE levels in utero
      ovarian and pancreatic tissue samples of C57BL/KsJ (+/?) control and (db/db)
      diabetic littermate mice was by high performance liquid chromatography (HPLC) and
      compared with the microspectrofluorometric histofluorescent (HF) localization of
      cellular and parenchymal NE. RESULTS: Diabetes-associated elevations in HPLC
      detectable tissue NE concentrations occurred in all pancreatic and reproductive
      tract tissue samples as compared to control-matched samples, whereas concurrent
      HF analysis revealed suppressed perivascular and parenchymal NE depositions in
      diabetic mice. CONCLUSIONS: These data suggest that progressive
      hypertriglyceridemia/lipidemia may suppress the effectiveness of intrinsic
      elevations in tissue NE concentrations from effectively counterregulating the
      deleterious effects of the hyperglycemic, type-2 diabetic condition.

PMID- 12218378
TI  - Progesterone inhibits rejection of xenogeneic transplants in the sheep uterus.
AB  - OBJECTIVES: One of the proposed roles of progesterone is to prevent maternal
      immunological destruction of the allogeneic conceptus. Here, it was demonstrated
      that progesterone allows survival of a xenotransplant placed in the uterine
      lumen. METHODS: Ovariectomized ewes, surgically prepared to have ligatures around
      each uterine horn, were given daily subcutaneous injections of 50 mg progesterone
      or vehicle (sesame oil). After 30 days of treatment, mouse hybridoma cells were
      transplanted to one ligated uterine horn and phosphate-buffered saline was
      injected into the other horn. The uterus was flushed after an additional 14 days
      of treatment and hybridoma cells were identified by immunofluorescence. RESULTS:
      Overall, hybridoma cells were recovered from 4 of 5 progesterone-treated ewes and
      1 of 5 vehicle-treated ewes. Immunohistochemical analysis of intercaruncular
      endometrium using antibodies towards CD8, gammadelta, and CD45R lymphocyte
      markers revealed that local presence of hybridoma cells caused a significant
      increase in CD8+ cells in all tissue compartments. While not significant, the
      numbers of CD8+ cells in the luminal and glandular epithelium were lower for
      progesterone-treated ewes. Progesterone tended to increase gammadelta T cell
      numbers in the glandular epithelium. CONCLUSIONS: Results demonstrate that
      xenograft rejection in the uterus is associated with an increase in CD8+ cells in
      the endometrium and that progesterone can inhibit uterine tissue graft rejection
      responses sufficiently to allow survival or delay rejection of xenograft tissue.

PMID- 12218379
TI  - Adult height in congenital hypothyroidism: prognostic factors and the importance
      of compliance with treatment.
AB  - OBJECTIVE: To study the growth, puberty and compliance of 66 hypothyroid children
      and to determine prognostic factors for adult height. PATIENTS: 66 children were
      included (12 boys, 54 girls). Aetiologies were 43 ectopic glands, 14 thyroid
      agenesis, 9 dyshormonogenesis. RESULTS: In girls the mean adult height was 164.7
      +/- 6.5 cm for a target height (TH) of 162.8 +/- 5.4 cm. In boys the mean adult
      height was 178.2 +/- 6.4 cm for a TH of 175.7 +/- 4.7 cm. Puberty development was
      normal. Children who exceeded their TH had an earlier start of treatment versus
      children who failed to reach their TH: 24.8 +/- 13.5 vs. 42.0 +/- 47.3 days, p =
      0.004. Delayed normalisation of TSH is a risk factor for bad compliance. Adequate
      correlations between treatment variables appeared only in children who exceeded
      their TH. CONCLUSIONS: TH, day of start of treatment and compliance with
      treatment are the main prognostic factors for adult height. Early detection of
      bad compliance is possible.

PMID- 12218380
TI  - Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma is
      associated with increased leptin levels in women with type-2 diabetes mellitus.
AB  - OBJECTIVE: To analyze the relationship between the peroxisome proliferator
      activated receptor-gamma (PPARgamma2) Pro12Ala variant and type-2 diabetes
      mellitus and its correlation with some cytokine determinants of insulin
      resistance such as tumor necrosis factor (TNF)-alpha and leptin. METHODS: The
      PPARgamma2 Pro12Ala genetic polymorphism was studied in 167 type-2 diabetic
      patients and 63 healthy controls. Serum leptin and plasma-soluble TNF-R2 were
      measured. RESULTS: Women carriers of the Pro12Ala mutation exhibited higher
      leptin levels than women non-carriers (median 31.4 vs. 17.5 ng/ml; p < 0.005).
      sTNF-R2 levels did not show differences between the two genotypes. Analysis by
      the multiple linear regression model of leptin-body mass index controlled by the
      PPARgamma2 genotype showed that leptin levels were determined by the Pro12Ala
      mutation in type-2 diabetic women but not in men. CONCLUSIONS: PPARgamma2 seems
      to be implicated in leptin homeostasis in type-2 diabetic women.

PMID- 12218381
TI  - Evaluation of high-dose estrogen and high-dose estrogen plus methyltestosterone
      treatment on cognitive task performance in postmenopausal women.
AB  - OBJECTIVES: To investigate the cognitive effects of high-dose oral estrogen alone
      or in combination with oral methyltestosterone in postmenopausal women. METHODS:
      Participants were tested with a randomized, double-blind design on the Identical
      Pictures, Cube Comparisons, Building Memory and Shape Memory tasks before and
      after 4 months of hormone treatment. RESULTS: Women receiving estrogen and
      methyltestosterone maintained a steady level of performance on the Building
      Memory task, whereas those receiving estrogen alone showed a decrease in
      performance. CONCLUSIONS: These results indicate that the addition of
      testosterone to high-dose estrogen replacement exerts a protective effect on
      memory performance in postmenopausal women.

PMID- 12218382
TI  - Chemokine receptors in the brain: their role in HIV infection and pathogenesis.

PMID- 12218383
TI  - Serum IgA of HIV-exposed uninfected individuals inhibit HIV through recognition
      of a region within the alpha-helix of gp41.
AB  - BACKGROUND: HIV-specific IgA is present in HIV-exposed uninfected individuals
      (EU) and neutralizes primary strains of HIV-1 in vitro. OBJECTIVES: To analyse
      the antigenic correlates of HIV-1 neutralization using HIV epitopes and IgA from
      EU and HIV-seropositive individuals. METHODS: Sera from six heterosexual couples
      discordant for HIV serostatus, six age-matched HIV-infected subjects and six
      healthy controls (HC; as negative controls) were analysed. IgA binding on HIV Env
      recombinant proteins was assayed. Serum IgA was affinity purified on specific Env
      peptides and tested in HIV neutralization using resting and activated peripheral
      blood mononuclear cells as target. Monoclonal antibody 2F5 was used as
      neutralizing positive control. BALB/c mice were immunized with specific gp41
      peptide and anti-sera were tested in syncytia formation and in HIV viral
      replication. RESULTS: IgA of EU exclusively bound an epitope within gp41; this
      epitope was restricted to residues 582-588 (QARILAV) and corresponded to the
      leucine zip motif in the alpha-helical region. IgA of HIV-positive patients
      recognized epitopes expressed both in gp120 and gp41; these epitopes were in the
      N-terminal portion of the extramembrane region. Additionally, IgA of EU and
      antisera of QARILAV-immunized Balb/C mice blocked syncytia formation and viral
      replication. The dose-dependent neutralization behaviour of specific QARILAV
      purified IgA was very similar to that obtained with monoclonal antibody 2F5.
      CONCLUSION: These results have important implications for the development of
      vaccines and therapeutical strategies against HIV infection.

PMID- 12218384
TI  - The protease inhibitor ritonavir inhibits the functional activity of the
      multidrug resistance related-protein 1 (MRP-1).
AB  - BACKGROUND: Efflux pumps situated on the plasma membrane, such as P-glycoprotein
      (Pgp) and the multidrug resistance related-protein 1 (MRP-1), have been shown to
      extrude HIV protease inhibitors from the cell. MRP-1 is present on many barrier
      sites throughout the body, such as the blood-brain and blood-testis interfaces
      and could reduce the concentration of protease inhibitors in these sanctuary
      sites for HIV-1 replication. Factors that modulate efflux pump function in vivo
      are poorly defined. OBJECTIVE: To analyze the inhibitory potential of the anti
      retroviral drugs indinavir, amprenavir, ritonavir, lamivudine or zidovudine to
      modulate MRP-1 function. METHODS: Effect of anti-HIV drugs on the efflux pump
      activity of MRP-1 was evaluated in the presence of increasing concentrations of
      human plasma, using UMCC-1/VP cells which stably over-express MRP-1. MRP-1
      activity was abrogated by probenecid. The potential of blocking MRP-1 function
      for an extended (3 day) time period, was also examined in MRP-1 over-expressing
      cells cultured with either probenecid or the anti-retroviral drugs and a
      cytotoxic compound (etoposide) that is transported by MRP-1. RESULTS: Ritonavir
      inhibited the functional activity of MRP-1 similarly to probenecid, as
      demonstrated by re-sensitization of MRP-1 over-expressing cells to cytotoxic
      effects of etoposide. Inhibition by ritonavir was inversely related to the
      concentration of human plasma added to the cells (r2 = 0.89). Other anti-HIV
      drugs didn't affect the MRP-1 mediated efflux of etoposide. CONCLUSIONS: These
      data may be exploitable to further improve sanctuary site concentrations of anti
      HIV or anti-cancer drugs by using ritonavir as a lead compound to develop more
      potent MRP-1 inhibitors.

PMID- 12218385
TI  - In patients on prolonged HAART, a significant pool of HIV infected CD4 T cells
      are HIV-specific.
AB  - OBJECTIVES: To examine the antigen specificities of HIV reservoir CD4 T cells in
      patients on prolonged and effective highly active antiretroviral therapy (HAART).
      DESIGN: Five HIV-infected patients, who were highly adherent to antiretroviral
      treatment, were selected on the basis of long-term undetectable plasma viral RNA
      on unmodified HAART. To investigate the antigen specificities of infected memory
      CD4 T cells, we examined the capacity of recall antigens, including HIV antigens,
      to induce virus production by peripheral blood mononuclear cells (PBMC). METHODS:
      To quantify CD4 T cells infected by replication-competent virus, and to determine
      their antigen specificities, we used a limiting dilution-based culture assay. CD8
      T cell-depleted PBMC at several cell densities were activated by using Tuberculin
      purified protein derivative, cytomegalovirus, or HIV-1 p24 with and without HIV-1
      Nef. RESULTS: We found that the pool of infected CD4 T cells includes HIV
      specific cells with apparent frequencies between 5- and 100-fold higher than
      those of the common specificities for cytomegalovirus or Tuberculin. CONCLUSION:
      Our findings suggest that a significant proportion of replication-competent HIV
      infected CD4 T cells in these patients are memory cells directed against HIV
      determinants. This may provide a rationale for the therapeutic use of recombinant
      HIV antigens to reduce the pool of HIV-reservoir cells.

PMID- 12218386
TI  - Dynamics of spontaneous HIV-1 specific and non-specific B-cell responses in
      patients receiving antiretroviral therapy.
AB  - OBJECTIVES: As spontaneous anti-HIV-1 antibody and IgG secretion by peripheral
      blood mononuclear cells (PBMC) reflect immune system activation by HIV-1
      antigens, we evaluated the impact of antiretroviral therapies on HIV-1 specific
      and non-specific B cell responses. METHODS: Anti-HIV-1 antibody and non-specific
      IgG were measured by ELISA in supernatants of PBMC cultured during 7 day from 30
      patients initiating an antiretroviral therapy at baseline, 8, 16, 24, 36 and 48
      weeks. RESULTS: An early and sustained fall in plasma viral load to below the
      detection limit (20 copies/ml) was observed in 17 sustained responder patients
      (SR), whereas HIV-1 RNA remained detectable in 13 others incomplete responders.
      In both groups, HIV-1 specific antibody secretion decreased significantly in
      parallel with plasma viral load and polyclonal immunoglobulin production became
      similar to that of PBMC controls. However, HIV-1 specific antibody production
      became negative in only six SR, exhibiting a greater increase of CD4 T-cell
      counts and higher levels of the spontaneous HIV-1 specific IgA secretion at
      baseline than the other SR. CONCLUSIONS: Antiretroviral therapy induced a rapid
      and dramatic decrease of spontaneous HIV-1 specific and non-specific B cell
      responses. These results pointed out that HIV-1 specific antibody secretion
      persisted in 11 out of 17 SR patients, suggesting persistent immune system
      activation by residual HIV-1 antigens.

PMID- 12218387
TI  - Immunological and virological factors at baseline may predict response to
      structured therapy interruption in early stage chronic HIV-1 infection.
AB  - BACKGROUND: The objective was to analyse which baseline factors could predict a
      favourable outcome after structured therapy interruption (STI). METHODS: Data of
      three Spanish pilot studies of STI in early stage chronic HIV-1-infected patients
      were analysed. A set of 37 variables at baseline was used. Plasma and tonsillar
      tissue viral load (VL), lymphocyte immunophenotyping and proliferative responses
      (LPR) to mitogens and specific antigens, and HIV-1 specific cytotoxic T
      lymphocyte responses were assessed at baseline. Response was defined as a VL set
      point after 6 months off antiretroviral therapy after the last interruption of <
      5000 copies/ml and 0.5 log(10) below baseline PVL before any antiretroviral
      therapy. RESULTS: After STI, the 44 patients were classified as follows: 18 (41%)
      as responders, 26 (59%) as non-responders. In the univariate analysis patients
      who responded had a significantly lower baseline level of CD4CD38 (P = 0.0068)
      and naive CD4 T cells (P = 0.03), and a higher level of memory CD4 T cells (P =
      0.03) and proliferative response to tetanus toxoid (TT) (P = 0.01) and HIV-1 p24
      (P = 0.03) than non-responders. A model incorporating five qualitative variables
      transformed according to the median value (CD4CD38, CD4 naive and memory T cells
      and stimulation index to TT and HIV-1 p24) at baseline could classify 97% of
      patients correctly (P = 0.0001). CONCLUSIONS: A level of memory CD4 T cells and
      proliferative response to recall antigens above the median may predict a good
      response to STI, suggesting that preserved memory response in CD4 T cells is
      important factor.

PMID- 12218388
TI  - Early and late effects of highly active antiretroviral therapy: a 2 year follow
      up of antiviral-treated and antiviral-naive chronically HIV-infected patients.
AB  - BACKGROUND: Control of HIV replication can be observed in highly active
      antiretroviral therapy (HAART)-treated and, occasionally, in HAART-naive
      patients. The immunological correlates of these situations were examined in a
      longitudinal study. DESIGN: A prospective study. Immunovirological analyses in 16
      chronically HIV-infected, HAART-naive patients (time 0) who started HAART.
      Fifteen patients (short-term HAART) were re-evaluated after 24 months (time 1).
      Results were compared with those of 30 patients who received HAART for more than
      12 months before the study period (long-term HAART) and were analysed at the same
      timepoints. Fifteen patients who were antiviral therapy naive (naive) at both
      timepoints were also studied. RESULTS: Over a 24-month period CD4 and CD8 cell
      counts and viraemia remained unchanged in naive and long-term HAART patients; CD4
      cell counts increased and viraemia diminished in short-term HAART individuals.
      Antigen-stimulated proliferation was unmodified in naive and short-term HAART
      patients, but improved in long-term HAART individuals. Gp160-stimulated IL-2 and
      IFN-gamma production was augmented in long-term HAART patients and marginally
      modified in other patients. IL-7 production was unmodified in naive individuals,
      augmented in short-term HAART patients, and diminished in long-term HAART
      patients. Chemokine production was similar in all patients. Naive patients showed
      the highest CD8 cell counts at both timepoints. CONCLUSION: HAART has a major
      impact on the outcome of HIV infection, even if functional immune modulation in
      HAART-treated patients is evident only after long periods of therapy. Low but
      detectable HIV replication in HAART-naive patients with preserved immune
      functions might not be associated with CD4 cell reduction, functional immune
      defects, or changes in viraemia.

PMID- 12218389
TI  - Mortality of HIV-1, HIV-2 and HIV-1/HIV-2 dually infected patients in a clinic
      based cohort in The Gambia.
AB  - OBJECTIVE: To assess and compare the mortality rates of patients with HIV-1, HIV
      2 or both infections (HIV-D) in the same population. DESIGN: Clinic-based cohort
      study. METHODS: HIV-seropositive patients aged 15 years and older who attended
      the Medical Research Council clinics in Fajara between May 1986 and September
      1997 were recruited. Clinical assessment using the Karnofsky score, CDC cell
      staging, WHO staging, and CD4 cell counts was performed at baseline. Patients
      attended clinic every 3 months; if they did not attend, they were visited at home
      by field workers to ascertain survival status. No patient was on antiretroviral
      therapy during the study period. RESULTS: Data from 1519 HIV-positive adult
      patients were analysed. A total of 746 patients had HIV-1, 666 HIV-2, and 107
      patients had HIV-D. A total of 828 patients (55%) died, and 161 (11%) were lost
      to follow-up. The median follow-up was 12 months (range 0-128). CD4 cell counts
      were available for 894 patients. Compared with HIV-1, the adjusted hazards ratio
      for mortality in the CD4 cell count category 500 cells/microl or greater was 0.50
      for HIV-2 (95% CI 0.28-0.88) and 1.27 (95% CI 0.51-3.7) for HIV-D. Among those
      with CD4 cell counts less than 500 cells/microl the mortality rates in HIV-2 and
      HIV-D were similar to those in HIV-1. DISCUSSION: HIV-2-infected patients with
      CD4 cell counts of 500 cells/microl and greater had a significantly lower
      mortality rate than HIV-1-infected patients. HIV-2-infected patients with
      advanced disease had the same poor prognosis as patients with HIV-1. Dually
      infected patients had mortality rates similar to HIV-1.

PMID- 12218390
TI  - High-density lipoprotein cholesterol is low in HIV-infected patients with
      lipodystrophic fat expansions: implications for pathogenesis of fat
      redistribution.
AB  - OBJECTIVE: To demonstrate relationships between plasma high-density lipoprotein
      (HDL) cholesterol and fat expansions in the fat redistribution syndrome. DESIGN:
      Patients who had significant buffalo humps or intra-abdominal fat (IAF)
      expansions were identified and their HDL levels were measured. Control patients
      were all those undergoing a single trial of antiretroviral treatment. Some
      patients answered a self-administered questionnaire concerning self-perceived fat
      expansions, and their responses were related to their HDL levels. In other
      patients, relationships were studied between IAF measured by cross-section
      computerized tomography scans and HDL levels. Finally, patients who had IAF > 70
      cm(2), were administered niacin, 3000 mg/day for > or = 6 months, in order to
      test whether raising HDL induced a decrease in IAF. RESULTS: Twenty-three
      patients with buffalo humps had mean HDL of 30.4 mg/dl; 47 HIV-positive controls
      had mean HDL of 41.9 mg/dl (P = 0.001). In 27 patients, IAF area and HDL were
      negatively correlated (r, 0.40; P = 0.04). Among these 27, the 17 patients with
      IAF area > 100 cm(2) had mean HDL of 35.3 mg/dl; the 10 patients with IAF area <
      100 cm(2) had mean HDL of 51 mg/dl (P < 0.05). The 24 patients who indicated in a
      questionnaire that they had self-perceived IAF expansion had a median HDL of 36.0
      mg/dl; the 20 who indicated that they did not have IAF expansion had a median HDL
      of 44.5mg/dl (P = 0.06). IAF decreased by 26.9% in 13 (81%) of the 16 patients
      who took niacin for 1 year; and the decrease in IAF was associated with a
      significant (P = 0.002) increase in HDL.

PMID- 12218391
TI  - A pilot study of cidofovir for progressive multifocal leukoencephalopathy in
      AIDS.
AB  - OBJECTIVE: To assess the safety, tolerability and effect of cidofovir for HIV-1
      associated progressive multifocal leukoencephalopathy. DESIGN: Prospective, open
      label study in nine AIDS Clinical Trials Units. PATIENTS AND METHODS: Twenty-four
      HIV-1-infected individuals, with neuroimaging and clinical findings consistent
      with PML, and symptoms for 90 days or less, whose diagnosis was confirmed by the
      detection of JC virus DNA in the cerebrospinal fluid or brain biopsy, received
      cidofovir 5 mg/kg intravenously at baseline and 1 week, followed by infusions
      every 2 weeks with the dose adjusted for renal function. Follow-up continued to
      24 weeks. The safety of cidofovir and changes in neurological examination scores
      between baseline and week 8 were assessed. RESULTS: Seventeen subjects were
      receiving potent antiretroviral agents. Survival at 12 weeks was 54%. The CD4
      cell count at entry was significantly associated with survival (P = 0.02). Five
      subjects discontinued treatment because of toxicity: a 50% or greater decrease in
      intraocular pressure in either eye in four, and proteinuria in one. Overall,
      magnetic resonance imaging abnormalities and neurological examination scores
      worsened. Only two subjects experienced a 25% or greater improvement in
      neurological examination scores at week 8, which were significantly better in
      subjects with HIV-1-RNA levels of 500 copies/ml or less at entry compared with
      those with HIV-1-RNA levels over 500 copies/ml (P = 0.05). CONCLUSION: Cidofovir
      did not improve neurological examination scores at week 8. However, such scores
      were significantly better in subjects who entered with suppressed plasma HIV-1
      RNA levels, which could be the result of control of HIV-1 infection itself or
      cidofovir.

PMID- 12218392
TI  - Highly active antiretroviral therapy enhances regression of cervical
      intraepithelial neoplasia in HIV-seropositive women.
AB  - OBJECTIVE: This study was undertaken to investigate the impact of highly active
      antiretroviral therapy (HAART) on the regression of cervical intraepithelial
      neoplasia (CIN) in HIV-infected women. DESIGN: Prospective study of 168 HIV
      infected women with evidence of CIN until regression to a lower grade or to
      normality (end-point) or until surgical treatment or last visit. Ninety-six
      patients received HAART. METHODS: Women were examined every 6 months by
      Papanicolaou smears, colposcopy, and biopsy if required. The probability of CIN
      regression was calculated using survival analysis. HAART was entered as a time
      dependent covariate according to the date of first prescription. RESULTS:
      Regression of CIN was observed in 67 (39.9%) women. The probability of regression
      at 12 months was significantly higher for high-grade CIN [23.8%; 95% confidence
      interval (CI), 14.2-33.5] than for low-grade lesions (14.8%; 95% CI, 7.0-22.6) (P
      = 0.04). The risk of regression of CIN was twice as high in women receiving HAART
      as compared with women not receiving HAART (relative hazard of regression, 1.93;
      95% CI, 1.14-3.29). There was a trend for a larger increase in CD4 cell counts
      among those women taking HAART and who showed regression as compared with those
      who did not regress. CONCLUSION: The positive impact of HAART on CIN regression
      may be associated with some restoration of specific immune reactivity. This is
      not sufficient enough, however, to modify the gynecological follow-up of HIV
      infected women.

PMID- 12218393
TI  - The incidence of lymphoma in the UK haemophilia population between 1978 and 1999.
AB  - OBJECTIVE: To determine the incidence of non-Hodgkin's lymphoma (NHL) and
      Hodgkin's disease (HD) in the UK haemophilia population during the 22 year period
      1978-1999. DESIGN AND METHODS: An analysis of patient data included on the UK
      Haemophilia Centre Doctors' Organisation lymphoma register. The number of cases
      of NHL and HD occurring in HIV-positive and negative patients in each 3-year
      period were compared with the expected incidence in the general male population.
      RESULTS: Eighty-nine cases of lymphoma were identified. Seventy-two cases (81%)
      occurred in HIV-positive patients (67 NHL, five HD), and 17 cases (19%) in HIV
      negative patients (nine NHL, eight HD). The incidence of NHL in the HIV-positive
      cohort was significantly increased, with a ratio of observed to expected cases of
      83.92 (P < 0.001) in the period 1985-1996. The ratio reduced to 42.15 during the
      period 1997-1999, presumably as a consequence of the introduction of highly
      active antiretroviral therapy (HAART). There was a significant excess of HD in
      HIV-positive patients, with an observed to expected ratio of 10.50 between 1985
      and 1999 (based on five cases, P < 0.001). During the whole observation period,
      there was a significant excess of HD in HIV-negative patients, with an observed
      to expected ratio of 2.66 (based on eight cases, P < 0.05). CONCLUSION: The
      incidence of lymphoma is significantly higher in HIV-positive UK haemophilia
      patients compared with HIV-negative individuals. Since the introduction of HAART,
      the incidence of lymphoma has tended to fall in the HIV-positive group.

PMID- 12218394
TI  - Forty-one near full-length HIV-1 sequences from Kenya reveal an epidemic of
      subtype A and A-containing recombinants.
AB  - OBJECTIVE: To further define the genetic diversity of HIV-1 in Kenya using
      approaches that clearly distinguish subtypes from inter-subtype recombinants.
      DESIGN: Near full genome sequencing and analysis were used, including sensitive
      new tools for detection and mapping of recombinants. METHODS: Purified peripheral
      blood mononuclear cell DNA from 41 HIV-1 positive blood donations collected from
      six hospitals across southern Kenya was used to amplify near full-length genomes
      by nested PCR. These were sequenced on an ABI 3100 automated sequencer and
      analyzed phylogenetically. RESULTS: Among 41 near full-length genomes, 25 were
      non-recombinant (61%) and 16 were recombinant (39%). Of the 25 pure subtypes, 23
      were subtype A, one was subtype C and one was subtype D. Most recombinants
      consisted of subtype A and either subtype C or subtype D; a few contained A2, a
      recently identified sub-subtype. Two A2/D recombinants had identical breakpoints
      and may represent a circulating recombinant form. A third A2/D recombinant had
      the same structure as a previously described Korean isolate, and these may
      constitute a second A2-containing circulating recombinant form. CONCLUSIONS: In
      Kenya, 93% of HIV-1 genomes were subtype A or A-containing recombinant strains.
      Almost 40% of all strains were recombinant. Vaccine candidates tested in Kenya
      should be based on subtype A strains, but the methods used for evaluation of
      breakthrough infections during future vaccine trials should be capable of
      identifying non-A subtypes, the A2 sub-subtype, and recombinants.

PMID- 12218395
TI  - The role of person-to-person transmission in an epidemiologic study of
      Pneumocystis carinii pneumonia.
AB  - OBJECTIVE: Recent laboratory studies suggest that may be transmitted from person
      to-person. Recent exposure to persons with pneumonia (PCP) among HIV-infected
      persons with and without PCP was assessed to evaluate the person-to-person
      transmission hypothesis. DESIGN: A case-control study design was used. METHODS:
      In Seattle and Los Angeles, a history of contact with persons with PCP was
      compared between HIV-infected patients with laboratory-confirmed PCP (n = 209)
      and HIV-infected patients with no history of PCP (n = 254). RESULTS: No
      association was found between past exposures to persons with PCP and an increased
      odds for PCP [odds ratio (OR), 0.6; 95% confidence interval (CI), 0.3-1.1] in the
      total study group. In addition, no association was observed when the analysis was
      restricted to cases and controls who were not on adequate PCP prophylaxis in the
      previous 3 months (OR, 0.7; 95% CI, 0.3-1.5). Most cases in Los Angeles (95%) and
      Seattle (96%) were not receiving PCP prophylaxis in the 3 months prior to a PCP
      diagnosis. Many controls in Los Angeles (54%) and Seattle (47%) were also not on
      prophylaxis. In addition, 23% of the Seattle cases and 42% of the Los Angeles
      cases were unaware of their HIV infection at the time of their PCP diagnosis.
      CONCLUSIONS: Although most participants were not on adequate prophylaxis, we
      found no evidence of person-to-person transmission of Pneumocystis carinii in a
      population with advanced HIV disease. The difficulty quantifying past exposures
      to persons with PCP is a limitation of this type of research.

PMID- 12218396
TI  - Rare and new V3 loop variants in HIV-1-positive long-term non-progressors from
      Rwanda.
AB  - We identified uncommon amino acid substitutions in the V3 loop regions of HIV-1
      strains infecting patients from Rwanda. Their frequency was greater in long-term
      non-progressors (LTNP) compared with late-stage patients (P = 0.006),
      particularly in a sequence region that has crucial interactions with the cell
      surface, and is highly relevant for the host's immune response. These variants
      might reflect a viral response to a strong immune pressure, or represent
      attenuated HIV-1 strains infecting LTNP in Rwanda.

PMID- 12218397
TI  - Effect of delavirdine on plasma lipids and lipoproteins in patients receiving
      antiretroviral therapy.
AB  - Plasma lipid and lipoprotein levels were measured at baseline and after 8 weeks
      of highly active antiretroviral therapy among patients receiving delavirdine with
      or without a protease inhibitor (PI). In patients receiving nucleoside reverse
      transcriptase inhibitors (NRTI) plus delavirdine, there was a statistically
      significant increase in cholesterol and HDL levels, whereas those receiving NRTI
      plus a PI had no significant change in their HDL levels. When delavirdine was
      combined with a PI, there was a more dramatic increase in both cholesterol and
      HDL concentrations.

PMID- 12218398
TI  - Decline in the rate of genotypic resistance to antiretroviral drugs in recent HIV
      seroconverters in Madrid.
AB  - Genotypic resistance to antiretroviral drugs was analysed in plasma from 57 acute
      or recent HIV seroconverters in Madrid. The overall prevalence of drug-associated
      primary resistance mutations was 25.8% in 1997-1999, but declined to 3.8% in 2000
      2001. The lower rate in recent years suggested that most new HIV infections
      derive from viraemic individuals unaware of their HIV- positive status, rather
      than from those failing antiretroviral treatment. Drug-resistance testing is thus
      not required before beginning antiretroviral therapy.

PMID- 12218399
TI  - Racial/ethnic differences in CD4 T cell count and viral load at presentation for
      medical care and in follow-up after HIV-1 infection.
AB  - The baseline characteristics of antiretroviral-naive patients were compared by
      ethnic/racial groups. First CD4 T cell counts were lower for Latino (P = 0.0004)
      and black patients (P = 0.10) when compared with white patients. First HIV-1-RNA
      levels were higher in Latino patients (P = 0.08), who were also more likely to
      present with major opportunistic infections (P < 0.004). Once in care, changes in
      CD4 T cell counts and viral loads over time did not differ significantly between
      groups.

PMID- 12218400
TI  - Provider inaccuracy in assessing adherence and outcomes with newly initiated
      antiretroviral therapy.
AB  - We studied the ability of providers to predict and estimate patient adherence to
      newly initiated highly active antiretroviral therapy (HAART). Nineteen providers
      referring 40 patients into an adherence study were surveyed. Widespread
      inaccuracy was found in providers' adherence predictions and estimates.
      Therefore, HAART should not be withheld solely on provider predictions of
      adherence. Providers should not rely on their own assessments when attempting to
      determine if patients are adhering to therapy.

PMID- 12218401
TI  - A novel potent strategy for induction of immunity to HIV-1 reverse transcriptase
      in primates.

PMID- 12218402
TI  - Nevirapine-induced neuropsychiatric complications, a class effect of non
      nucleoside reverse transcriptase inhibitors?

PMID- 12218403
TI  - Efavirenz-induced catatonia.

PMID- 12218404
TI  - Acute salicylate intoxication after percutaneous absorption in an HIV patient
      treated for psoriasis.

PMID- 12218405
TI  - Bacterial endocarditis: a role for Mycobacterium tuberculosis?

PMID- 12218406
TI  - Treating tuberculosis in AIDS patients: when to start and how long to keep giving
      drugs?

PMID- 12218407
TI  - Explosive spread and high prevalence of HIV infection among injecting drug users
      in Togliatti City, Russia.
AB  - OBJECTIVE: To establish the prevalence of antibodies to HIV (anti-HIV) and
      associated risk factors among injecting drug users (IDU) in Togliatti City,
      Samara Oblast, Russian Federation. DESIGN: An unlinked anonymous cross-sectional
      community recruited survey with oral fluid sample collection. METHODS: Between
      September and October 2001, 426 IDU were recruited by trained fieldworkers.
      Participants completed an interviewer administered questionnaire, and oral fluid
      samples were tested for anti-HIV. Univariate and multivariate analyses compared
      potential risk factors for anti-HIV. RESULTS: Anti-HIV prevalence was 56%
      (234/418). Three-quarters of anti-HIV-positive IDU (74%) were unaware of their
      positive status. In an adjusted model, the odds of HIV infection were higher
      among IDU who had ever injected home-produced drugs, who reported injecting with
      used needles and syringes in the past 4 weeks, and who were living in one
      particular district of the city (Komsomolksii). CONCLUSION: The high prevalence
      of HIV, and a recent increase in HIV detected through routine screening tests
      since 2000, suggests that an explosive epidemic has occurred among IDU in
      Togliatti City. In the face of currently inadequate HIV prevention coverage among
      IDU, this has urgent implications for maximizing the distribution of sterile
      injecting equipment as well as for enhancing sexual risk reduction. Recognizing
      that it is likely that similar explosive epidemics are taking place in other
      Russian cities, we recommend community-wide HIV prevention coverage supported by
      city and state policies oriented to harm reduction.

PMID- 12218408
TI  - Excess DNA mutations seen in babies whose HIV-infected mothers took
      antiretroviral drugs.

PMID- 12218409
TI  - Imaging amyloid-beta deposits in vivo.
AB  - Alzheimer disease (AD) is an illness that can only be diagnosed with certainty
      with postmortem examination of brain tissue. Tissue samples from afflicted
      patients show neuronal loss, neurofibrillary tangles (NFTs), and amyloid-beta
      plaques. An imaging technique that permitted in vivo detection of NFTs or amyloid
      beta plaques would be extremely valuable. For example, chronic imaging of senile
      plaques would provide a readout of the efficacy of experimental therapeutics
      aimed at removing these neuropathologic lesions. This review discusses the
      available techniques for imaging amyloid-beta deposits in the intact brain,
      including magnetic resonance imaging, positron emission tomography, single photon
      emission computed tomography, and multiphoton microscopy. A variety of agents
      that target amyloid-beta deposits specifically have been developed using one or
      several of these imaging modalities. The difficulty in developing these tools
      lies in the need for the agents to cross the blood-brain barrier while
      recognizing amyloid-beta with high sensitivity and specificity. This review
      describes the progress in developing reagents suitable for in vivo imaging of
      senile plaques.

PMID- 12218410
TI  - Effect of basal conditions on the magnitude and dynamics of the blood oxygenation
      level-dependent fMRI response.
AB  - The effect of the basal cerebral blood flow (CBF) on both the magnitude and
      dynamics of the functional hemodynamic response in humans has not been fully
      investigated. Thus, the hemodynamic response to visual stimulation was measured
      using blood oxygenation level-dependent (BOLD) functional magnetic resonance
      imaging (fMRI) in human subjects in a 7-T magnetic field under different basal
      conditions: hypocapnia, normocapnia, and hypercapnia. Hypercapnia was induced by
      inhalation of a 5% carbon dioxide gas mixture and hypocapnia was produced by
      hyperventilation. As the fMRI baseline signal increased linearly with expired CO2
      from hypocapnic to hypercapnic levels, the magnitude of the BOLD response to
      visual stimulation decreased linearly. Measures of the dynamics of the visually
      evoked BOLD response (onset time, full-width-at-half-maximum, and time-to-peak)
      increased linearly with the basal fMRI signal and the end-tidal CO2 level. The
      basal CBF level, modulated by the arterial partial pressure of CO2, significantly
      affects both the magnitude and dynamics of the BOLD response induced by neural
      activity. These results suggest that caution should be exercised when comparing
      stimulus-induced fMRI responses under different physiologic or pharmacologic
      states.

PMID- 12218411
TI  - Expression of brain-specific angiogenesis inhibitor 2 (BAI2) in normal and
      ischemic brain: involvement of BAI2 in the ischemia-induced brain angiogenesis.
AB  - Previously, the authors cloned and characterized murine brain-specific
      angiogenesis inhibitor 1 (mBAI1). In this study, the authors cloned mBAI2 and
      analyzed its functional characteristics. Northern and Western blot analyses
      demonstrated a unique developmental expression pattern of mBAI2 in the brain. The
      expression level of mBAI2 appeared to increase as the development of the brain
      progressed. Reverse transcription-polymerase chain reaction (RT-PCR) analyses
      demonstrated the existence of alternative splice variants of mBAI2, which were
      defective in parts of type I repeat of thrombospondin or the third cytoplasmic
      loop of the seven-span transmembrane domain that were considered essential to the
      functions of mBAI2. The expressions of spliced variants in the brain were
      differently regulated compared with wild-type mBAI2 during development and
      ischemic conditions. In situ hybridization analyses of the brain showed the same
      localization of BAI2 as BAI1, such as in most neurons of cerebral cortex. In the
      in vivo focal cerebral ischemia model and the in vitro hypoxic cell culture model
      with cobalt, BAI2 expression decreased after hypoxia and preceded the increased
      expression of vascular endothelial growth factor (VEGF). RT-PCR analysis of
      antisense BAI2 cDNA-transfected SHSY5Y cells showed an increased VEGF expression
      as well as a decreased BAI2 expression. Immunohistochemical study of focal
      ischemic cortex showed that the regional localization of decreased BAI2 was
      related to the formation of new vessels. These results suggest that the brain
      specific developmental expression pattern of angiostatic BAI2 is correlated with
      the decreased neovascularization in the adult brain, and that angiostatic BAI2
      participates in the ischemia-induced brain angiogenesis in concert with
      angiogenic VEGF.

PMID- 12218413
TI  - New method for the quantitative assessment of axonal damage in focal cerebral
      ischemia.
AB  - Quantification of damage in both grey and white matter is required for
      comprehensive assessment of neuroprotective drug efficacy. Although methods for
      quantification of neuronal perikaryal damage after ischemia are well established,
      assessment of axonal damage has been limited. This article describes a new method
      for quantitation of axonal injury after middle cerebral artery (MCA) occlusion in
      rats and its application to the study of the antioxidant ebselen. The methodology
      is based on immunohistochemical detection of amyloid precursor protein (APP)
      accumulation in deformed, swollen axons in zones of ischemia. Sixty-five axon
      rich sites throughout the MCA territory are assessed for the presence (scored 1)
      or absence (scored 0) of accumulated APP in axonal swellings. Scores for
      individual sites are summated in predefined neuroanatomic regions (e.g. corpus
      callosum), stereotaxic levels, or for a total hemisphere APP score. Both intra
      rater and inter-rater reproducibility were high (r = 0.87 and 0.80,
      respectively). Ebselen (1 mg kg(-1) hr(-1), intravenously) significantly reduced
      the volume of neuronal perikaryal damage (24%, P < 0.01) and axonal damage (total
      APP score reduced from 27 [23.9 to 35.1, 95% CI] to 21.5 [18.2 to 23.3], P =
      0.002 with ebselen treatment). In conclusion, a robust and generally applicable
      method is described for assessing pathologic features in myelinated fiber tracts
      that is sensitive for detection of drug effects on axonal damage.

PMID- 12218412
TI  - Quantitative real-time RT-PCR analysis of inflammatory gene expression associated
      with ischemia-reperfusion brain injury.
AB  - Ischemia-reperfusion brain injury initiates an inflammatory response involving
      the expression of adhesion molecules and cytokines, some of which are regulated
      by the nuclear transcription factor NF-kappaB. In this study the authors examined
      mRNA expression levels for several important genes associated with inflammation
      at five time points (3, 6, 12, 24, and 72 hours) after transient middle cerebral
      artery occlusion (MCAO) in Sprague-Dawley rats. A sensitive and quantitative
      technique (TaqMan real-time QRT-PCR) was used to simultaneously measure mRNA
      levels for key cell adhesion molecules and inflammatory cytokines. Gene
      expression increased significantly in the injured hemisphere for interleukin (IL)
      1beta (12-fold increase at 24 hours), IL-6 (25-fold increase at 6 hours) and ICAM
      1 (4-fold increase at 24 hours), and the interhemispheric differences for these
      genes were significant for every time point examined (P < 0.05 for all values).
      Tumor necrosis factor-alpha mRNA was upregulated in the injured versus uninjured
      hemisphere from 3 to 24 hours (5-fold increase at 6 hours), while E-selectin
      showed a significant increase in mRNA levels from 6 to 24 hours after MCAO (10
      fold increase at 6 hours) (P < 0.05 for all values). VCAM-1 mRNA levels did not
      respond differentially to injury at any time point between the two brain
      hemispheres. At all time points examined, activated NF-kappaB immunoreactivity
      was observed in cells throughout the infarct-damaged tissue. These results are
      consistent with the proinflammatory properties of the induced molecules, which
      are involved in the initiation of the inflammatory cascade, and may thus
      contribute to secondary cellular responses that lead to further brain damage.

PMID- 12218414
TI  - Grey matter and white matter ischemic damage is reduced by the competitive AMPA
      receptor antagonist, SPD 502.
AB  - Protection of both grey and white matter is important for improvement in stroke
      outcome. In the present study the ability of a competitive alpha-amino-3-hydroxy
      5-methyl-4-isoxazole propionic acid (AMPA) antagonist to protect axons,
      oligodendrocytes, and neuronal perikarya, was examined in a rodent model of
      transient focal cerebral ischemia. SPD 502 (8-methyl-5-(4-( 
      dimethylsulfamoyl)phenyl)-6,7,8,9-tetrahydro-1H-pyrrolo[3,2h]-isoquinoline-2,3
      dione-3-o(4-hydroxybutyricacid-2-yl)oxime) was administered as an intravenous
      bolus (16 mg/kg) 15 minutes before transient (3-hour) middle cerebral artery
      (MCA) occlusion, followed by an intravenous infusion (16 mg kg(-1) hr(-1)) of the
      drug for 4 hours. Twenty-one hours after ischemia, axonal damage was reduced by
      45% (P = 0.006) in the SPD 502-treated group compared with the vehicle. The
      anatomic extent of ischemically damaged oligodendrocytes, determined by Tau1
      immunoreactivity, was reduced in the cerebral cortex by 53% (P = 0.024) in SPD
      502-treated rats compared with vehicle-treated rats, but there was minimal effect
      in the subcortex. The volume of neuronal perikaryal damage after MCA occlusion
      was significantly reduced by SPD 502 in the cerebral cortex (by 68%; P = 0.005),
      but there was minimal change in the subcortex with drug treatment. The AMPA
      receptor antagonist significantly reduced the anatomic extent of lipid
      peroxidation (assessed as the volume of 4-hydroxynonenol immunoreactivity), and
      this may have contributed to its ability to protect multiple cell types in
      ischemia. The data demonstrate that AMPA blockade protects both grey and white
      matter from damage induced by transient focal ischemia.

PMID- 12218415
TI  - Phosphorylation of neuronal nitric oxide synthase at Ser847 by CaM-KII in the
      hippocampus of rat brain after transient forebrain ischemia.
AB  - The authors previously demonstrated that Ca2+/calmodulin (CaM)-dependent protein
      kinase IIalpha (CaM-KIIalpha) can phosphorylate neuronal nitric oxide synthase
      (nNOS) at Ser847 and attenuate NOS activity in neuronal cells. In the present
      study, they established that forebrain ischemia causes an increase in the
      phosphorylation of nNOS at Ser847 in the hippocampus. This nNOS phosphorylation
      appeared to be catalyzed by CaM-KII: (1) it correlated with the
      autophosphorylation of CaM-KIIalpha; (2) it was blocked by the CaM-KII inhibitor,
      KN-93; and (3) nNOS and CaM-KIIalpha were found to coexist in the hippocampus.
      Examination of the spatial relation between nNOS and CaM-KIIalpha in the brain
      revealed coexistence in the hippocampus but not in the cortex during reperfusion,
      with a concomitant increase in autophosphorylation of CaM-KIIalpha. The
      phosphorylation of nNOS at Ser847 probably takes place in nonpyramidal
      hippocampal neurons, which increased after 30 minutes of reperfusion in the
      hippocampus, whereas no significant increase was detected in the cortex. An
      intraventricular injection of KN-93 significantly decreased the phosphorylation
      of nNOS in the hippocampus. These results point to CaM-KII as a protein kinase,
      which by its colocalization may attenuate the activity of nNOS through its Ser847
      phosphorylation, and may thus contribute to promotion of tolerance to
      postischemic damage in hippocampal neurons.

PMID- 12218416
TI  - Persistent phosphorylation of synaptic proteins following middle cerebral artery
      occlusion.
AB  - Transient cerebral ischemia following 1 to 2 hours of middle cerebral artery
      occlusion (MCAO) in the rat leads to infarction, which can be diminished by
      synaptic transmission modulators, implying aberrant cell signaling in the
      pathogenetic process. The authors report here changes in the levels of tyrosine
      phosphorylated proteins (PTyr) and calcium calmodulin kinase II (CaMKII)
      phosphorylation of Thr 286, in synaptosomal, particulate, and cytosolic fractions
      of different cortical areas following 1 or 2 hours of MCAO, or 2 hours of MCAO
      followed by 2 hours of reperfusion. At the end of 2-hour MCAO, PTyr, and in
      particular the pp180, indicative of NR2A/B subunit, increased in the synaptosomal
      fraction in less ischemic areas while it decreased in more severe ischemic
      regions. During reperfusion, phosphorylation increased at least 2-fold in all
      reperfused areas. During 2 hours of MCAO, the phosphorylation of CaMKII increased
      8- to 10-fold in the synaptosomal fraction in all ischemic brain regions. During
      reperfusion, the phospho-CaMKII levels remained elevated by approximately 300%
      compared with the contralateral hemisphere (control). There was no increase in
      phospho-CaMKII in the cytosolic fraction at any time during or following ischemia
      in any of the brain regions examined. The authors conclude that both tyrosine
      kinase coupled pathways, as well as CaMKII-mediated cellular processes associated
      with synaptic activity, are strongly activated during and particularly following
      MCAO. These results support the hypothesis that aberrant cell signaling may
      contribute to ischemic cell death and dysfunction, and that selective modulators
      of cell signaling may be targets for pharmacological intervention against
      ischemic brain damage.

PMID- 12218417
TI  - Transforming growth factor-beta1-modulated cerebral gene expression.
AB  - Transforming growth factor-beta1 (TGF-beta1) plays a central role in the response
      of the brain to different types of injury. Increased TGF-beta1 has been found in
      the central nervous system of patients with acute or chronic disorders such as
      stroke or Alzheimer disease. To further define the molecular targets of TGF-beta1
      in cerebral tissues, a selection of high-density cDNA arrays was used to
      characterize the mRNA expression profile of 7,000 genes in transgenic mice
      overexpressing TGF-beta1 from astrocytes as compared with the wild-type line.
      Selected findings were further evaluated by reverse transcription-polymerase
      chain reactions from independent transgenic and wild-type mice. Furthermore, the
      expression pattern of seven selected genes such as Delta-1, CRADD, PRSC-1, PAI-1,
      Apo-1/Fas, CTS-B, and TbetaR-II were confirmed in either cultured cortical
      neurons or astrocytes following TGF-beta1 treatment. The authors' observations
      enlarge the repertoire of known TGF-beta1-modulated genes and their possible
      involvement in neurodegenerative processes.

PMID- 12218418
TI  - The phosphodiesterase 5 inhibitor sildenafil has no effect on cerebral blood flow
      or blood velocity, but nevertheless induces headache in healthy subjects.
AB  - Cyclic nucleotides are important hemodynamic regulators in many tissues. Glyceryl
      trinitrate markedly dilates large cerebral arteries and increases cGMP. Here, the
      authors study the effect of sildenafil, a selective inhibitor of cGMP-hydrolyzing
      phosphodiesterase 5 on cerebral hemodynamics and headache induction. Ten healthy
      subjects were included in a double-blind, placebo-controlled crossover study
      where placebo or sildenafil 100 mg (highest therapeutic dose) were administered
      on two separate days. Blood velocity in the middle cerebral artery (Vmca) was
      recorded by transcranial Doppler, and regional cerebral blood flow in the
      perfusion area of the middle cerebral artery (rCBFmca) was measured using single
      photon emission computed tomography and xenon inhalation. Radial and temporal
      artery diameters were studied using high-frequency ultrasound. Blood pressure and
      heart rate were recorded repeatedly. Headache responses and tenderness of
      pericranial muscles were scored verbally. Sildenafil caused no significant
      changes in rCBFmca, Vmca, or in temporal or radial artery diameter, but heart
      rate increased and diastolic blood pressure decreased significantly compared to
      placebo. Despite the lack of cerebral arterial dilatation, sildenafil caused
      significantly more headache than placebo. The present results show that
      sildenafil 100 mg does not dilate cerebral or extracerebral arteries but
      nevertheless causes headache, which may be attributed to nonvascular mechanisms.

PMID- 12218419
TI  - In vivo receptor assay with multiple ligand concentrations: an equilibrium
      approach.
AB  - The ligand-receptor binding potential determined by PET studies at high ligand
      specific radioactivity reflects both the receptor density and ligand-receptor
      affinity. This ambiguity has been resolved by various methods based on the
      administration of multiple unlabeled ligand concentrations. The authors aimed to
      implement and refine an approach to multiple ligand concentration receptor assay
      that combined maximum simplicity and a minimum of assumptions and model
      dependence that would nonetheless reliably distinguish density from affinity
      effects. The approach uses administration by bolus followed by infusion to obtain
      a true equilibrium between bound ligand and the other components of the ligand
      concentration, and does not require measurements of ligand in blood plasma. Four
      approaches to the optimization of the desired density and affinity parameters
      from the measured equilibrium data were implemented and compared in the analysis
      of raclopride studies performed in both normal control and MPTP-lesioned nonhuman
      primates. The authors conclude that the method is simple enough for routine use
      and yet reliable enough to apply in ongoing studies of both chronic and acute
      drug effects in the dopamine system.

PMID- 12218420
TI  - Use of cerebrovascular reactivity in patients with symptomatic major cerebral
      artery occlusion to predict 5-year outcome: comparison of xenon-133 and iodine
      123-IMP single-photon emission computed tomography.
AB  - The aim of this prospective study was to investigate whether decreased
      cerebrovascular reactivity to acetazolamide, as determined by single-photon
      emission computed tomography (SPECT), is an independent predictor of the 5-year
      risk of subsequent stroke in patients with symptomatic major cerebral artery
      occlusion. Cerebrovascular reactivity to acetazolamide in the middle cerebral
      artery (MCA) territory ipsilateral to the occluded artery was determined on the
      basis of two different methodologies: cerebral blood flow (CBF) percent change
      obtained quantitatively from xenon-133 (133Xe) SPECT, and asymmetry index (AI)
      percent change obtained qualitatively from N-isopropyl-p-[123I]-iodoamphetamine
      (IMP) SPECT. Seventy patients with unilateral internal carotid artery or MCA
      occlusion were divided into two groups within each SPECT methodology (normal or
      decreased CBF percent change and AI percent change) and followed up for 5 years.
      Cumulative recurrence-free survival rates for patients with decreased CBF percent
      change were significantly lower than for those with normal CBF percent change (P
      = 0.0205). There was no significant difference in cumulative recurrence-free
      survival rates between patients with decreased AI percent change and those with
      normal AI percent change. Only decreased CBF percent change was a significant
      independent predictor of stroke recurrence (P = 0.0051). The present study
      demonstrated that decreased cerebrovascular reactivity to acetazolamide
      determined quantitatively by 133Xe SPECT is an independent predictor of the 5
      year risk of subsequent stroke in patients with symptomatic major cerebral artery
      occlusion, and that the qualitative method using 123I-IMP SPECT is a poor
      predictor of the risk of subsequent stroke in this type of patient.

PMID- 12218421
TI  - Absolute quantification of cerebral blood flow with magnetic resonance,
      reproducibility of the method, and comparison with H2(15)O positron emission
      tomography.
AB  - While H2(15)O positron emission tomography (PET) is still the gold standard in
      the quantitative assessment of cerebral perfusion (rCBF), its technical
      challenge, limited availability, and radiation exposure are disadvantages of the
      method. Recent work demonstrated the feasibility of magnetic resonance (MR) for
      quantitative cerebral perfusion imaging. There remain open questions, however,
      especially regarding reproducibility. The main purpose of this study was to
      assess the accuracy and reproducibility of MR-derived flow values to those
      derived from H2(15)O PET. Positron emission tomography and MR perfusion imaging
      was performed in 20 healthy male volunteers, who were chronic smokers, on day 1
      and day 3 of a 4-day hospitalization. Subjects were randomly assigned to one of
      two groups, each with 10 subjects. One group was allowed to smoke as usual during
      the hospitalization, while the other group stopped smoking from day 2. Positron
      emission tomography and MR images were coregistered and rCBF was determined in
      two regions of interest, defined over gray matter (gm) and white matter (wm),
      yielding rCBF(PET)gm, rCBF(MR)gm, rCBF(PET)wm, and rCBF(MR)wm. Bland-Altman
      analysis was used to investigate reproducibility by assessing the difference
      rCBFday3 - rCBFday1 in eight continual-smoker volunteers. The analysis showed a
      good reproducibility for PET, but not for MR. Mean +/- SD of the difference
      rCBFday3 - rCBFday1 in gray matter was 6.35 +/- 21.06 and 0.49 +/- 5.27 mL x min(
      1) x 100 g(-1) for MR and PET, respectively; the corresponding values in white
      matter were 2.60 +/- 15.64 and -1.14 +/- 4.16 mL x min(-1) x 100 g(-1). The Bland
      Altman analysis was also used to assess MRI and PET agreement comparing rCBF
      measured on day 1. The analysis demonstrated a reasonably good agreement of MR
      and PET in white matter (rCBF(PET)wm - rCBF(MR)wm; -0.09 +/- 7.23 mL x min(-1) x
      100 g(-1)), while in gray matter a reasonable agreement was only achieved after
      removing vascular artifacts in the MR perfusion maps (rCBF(PET)gm - rCBF(MR)gm; 
      11.73 +/- 14.52 mL x min(-1) x 100 g(-1)). In line with prior work, these results
      demonstrate that reproducibility was overall considerably better for PET than for
      MR. Until reproducibility is improved and vascular artifacts are efficiently
      removed, MR is not suitable for reliable quantitative perfusion measurements.

PMID- 12218422
TI  - Reduced aggression in two inpatient children with the treatment of their sleep
      disorder.

PMID- 12218423
TI  - Effects of risperidone on conduct and disruptive behavior disorders in children
      with subaverage IQs.
AB  - OBJECTIVE: To determine whether risperidone is effective in reducing symptoms of
      disruptive behaviors (such as aggression, impulsivity, defiance of authority
      figures, and property destruction) associated with conduct disorder, oppositional
      defiant disorder, and disruptive behavior disorder-not otherwise specified in
      children with subaverage IQs. METHOD: The trial consisted of a 1-week, single
      blind, placebo run-in period and was followed by a 6-week, double-blind, placebo
      controlled period. One hundred ten children (aged 5-12 years inclusive) with an
      IQ of 36-84 with a disruptive behavior disorder and a score of at least 24 on the
      Conduct Problem subscale of the Nisonger Child Behavior Rating Form (NCBRF) were
      enrolled. Eighty percent of subjects had comorbid attention-deficit/hyperactivity
      disorder (ADHD). Risperidone doses ranged from 0.02 to 0.06 mg/kg per day.
      Subjects were rated on the NCBRF, Aberrant Behavior Checklist, Behavior Problems
      Inventory, Clinical Global Impressions (CGI), modified California Verbal Learning
      Test (CVLT), and a continuous performance task (CPT). RESULTS: The intention-to
      treat analysis of risperidone-treated subjects showed a significant (p < .001)
      reduction in mean scores (from 33.4 at baseline to 17.6 at end point; 47.3%
      reduction) versus placebo-treated subjects (mean baseline of 32.6 to 25.8 at end
      point; 20.9% reduction) on the Conduct Problem subscale of the NCBRF. Between
      group differences in favor of risperidone were seen as early as week 1 and were
      significant at all post-baseline visits. Other subscales showed significant
      improvement with risperidone compared with placebo. CGI scale ratings of
      improvement showed highly significant gains for risperidone over placebo. A
      subanalysis demonstrated that the effect of risperidone was unaffected by
      diagnosis, presence/absence of ADHD, psychostimulant use, IQ status, and
      somnolence. Risperidone produced no changes on the cognitive variables
      (CPT/modified CVLT). The most common side effects included somnolence, headache,
      appetite increase, and dyspepsia. Side effects related to extrapyramidal symptoms
      were reported in 7 (13.2%) and 3 (5.3%) of the subjects in the risperidone and
      placebo groups, respectively (p = .245). CONCLUSIONS: Risperidone appears to be
      an adequately tolerated and effective treatment in children with subaverage IQs
      and severe disruptive behaviors such as aggression and destructive behavior.

PMID- 12218424
TI  - Sertraline pharmacokinetics and dynamics in adolescents.
AB  - OBJECTIVE: To determine the pharmacokinetics of sertraline in adolescents and
      assess its effect on a surrogate marker of serotonin transport. METHOD:
      Pharmacokinetic parameters of a single 50-mg dose of sertraline were determined
      in 10 adolescents. Steady-state withdrawal kinetics were determined in 12
      adolescents taking 50 mg/day and in 6 adolescents taking 100 to 150 mg/day.
      Platelet serotonin reuptake was measured before and after 2 weeks of daily 50-mg
      dosing. RESULTS: The mean steady-state half-life of 50 mg was significantly
      shorter (15.3 +/- 3.5 hours) than the single-dose half-life (26.7 +/- 5.2 hours;
      t = 6.4, p < .001) and the steady-state half-life at 100 to 150 mg/day (20.4 +/-
      3.4 hours; t = 2.9, p = .01). Platelet serotonin reuptake was inhibited by 61 +/-
      15% after approximately 2 weeks of sertraline 50 mg/day. CONCLUSIONS: The half
      life of sertraline 50 mg becomes significantly shorter from the initial dose to
      steady-state, and many adolescents may benefit from twice-per-day dosing. The
      steady-state half-life increases as the dose increases. The moderate levels of
      platelet reuptake inhibition at 50 mg/day indicate that most adolescents may need
      sertraline doses higher than 50 mg/day to attain a therapeutic response.

PMID- 12218425
TI  - Serum creatine kinase levels in untreated hospitalized adolescents during acute
      psychosis.
AB  - OBJECTIVE: Psychosis-associated creatine kinase (CK)-emia (PACK) is a common and
      pronounced laboratory abnormality that accompanies adult psychotic conditions.
      Adult PACK is a relatively consistent individual trait. The authors investigated
      whether psychotic adolescents also present with such PACK characteristics.
      METHOD: Participants were 127 newly admitted, drug-free, psychotic Israeli
      adolescents. Measures were baseline psychotic severity, serum creatine kinase
      (CK0), lactate dehydrogenase (LDH0), glutamate oxaloacetate transaminase (SGOT0),
      white blood cell count (WBC0), urine myoglobulin, and the repeated CK (RepCK)
      measurements taken during recurrent psychotic episodes. RESULTS: Schizophrenia
      was the prevalent diagnosis (53%). CK0 levels did not correlate with the severity
      of the psychotic symptoms. Twenty-one percent of patients had a CK0 level >1,000
      IU/L. CK0 and RepCK levels were higher in males than in females (p < or = .001)
      and in Jewish Sephardi patients than in Ashkenazi patients (p < .007). There was
      no difference by diagnosis. Logarithmic (Ln) CK0 correlated with RepCK, SGOT0,
      LDH0, and WBC0 (r = +0.32-0.74, p < .001) but correlated inversely with serum
      cholesterol0 (r = -0.36, p = .002) in males. Even prominent PACK was not
      associated with myoglobinuria. These findings remained significant among the
      younger patients (aged <18 years). In males from this subgroup, LnCK0 also
      correlated with age (p < .007) but not with weight. CONCLUSIONS: In psychotic
      adolescents, PACK is common, is more prevalent among males, is independent of
      diagnosis, is influenced by ethnicity, and tends to recur.

PMID- 12218426
TI  - Immunity in adolescents with major depression.
AB  - OBJECTIVE: The association between major depression (MD) and altered immunity
      appears to be age-related, with differing immune changes found in prepubertal
      children, young adults, and older adults. There is limited information concerning
      immunity in adolescents with MD. METHOD: Thirty-six otherwise healthy medication
      free adolescents (aged 14-20; 23 female) from a community sample, meeting
      Diagnostic Interview Schedule for Children DSM-III-R criteria for unipolar MD,
      were compared with 36 nondepressed adolescents matched by gender, age, and racial
      background. A battery of quantitative and functional immune measures was
      obtained. RESULTS: MD adolescents had increased (p < .05) circulating lymphocytes
      and lymphocyte subsets; however, altered distribution of lymphocyte subsets was
      found only for activated T (HLA-DR+) cells (p < .004) and, possibly, natural
      killer (NK) (CD56+) cells (p < .06), each showing lower percentages in the MD
      adolescents. Concanavalin A (but not phytohemagglutinin or pokeweed mitogen)
      mitogen response was lower in the MD adolescents (p < .02). NK cell activity was
      elevated at higher effector-target ratios (p < .001), an effect not associated
      with the number of circulating CD56+ (NK) cells. CONCLUSIONS: Depressed
      adolescents showed changes in immune measures that have been found to be altered
      in other MD groups, although the pattern of effects differs.

PMID- 12218427
TI  - The Pediatric Anxiety Rating Scale (PARS): development and psychometric
      properties.
AB  - OBJECTIVE: To describe the development and psychometric properties of the
      Pediatric Anxiety Rating Scale (PARS), a clinician-rated instrument for assessing
      the severity of anxiety symptoms associated with common DSM-IV anxiety disorders
      (social phobia, separation anxiety disorder, and generalized anxiety disorder) in
      children. METHOD: As part of a multisite study of the efficacy of fluvoxamine,
      128 children (aged 6-17) and their parents were interviewed weekly with the PARS.
      Data from multiple raters on a subsample of children (using live and videotaped
      interviews) were used to evaluate interrater reliability. Internal consistency,
      test-retest reliability, and validity (convergent, divergent) also were
      evaluated. RESULTS: The PARS showed high interrater reliability, adequate test
      retest reliability, and fair internal consistency. Convergent and divergent
      validity were satisfactory. PARS scores were sensitive to treatment and
      paralleled change in other measures of anxiety symptoms and global improvement.
      CONCLUSIONS: The PARS is a useful clinician-rated instrument for assessing
      pediatric anxiety symptoms, severity, and impairment, particularly in treatment
      studies. Further study of the psychometric properties is warranted.

PMID- 12218429
TI  - Psychological measures of prenatal stress as predictors of infant temperament.
AB  - OBJECTIVE: To examine, in a prospective study, whether maternal stress during
      pregnancy is related to infant temperament. METHOD: Self-report data on various
      aspects of prenatal stress were collected from nulliparous women in early
      pregnancy. Infant temperament was measured at 3 and 8 months by direct
      observation and by parent report. RESULTS: Complete data were available for 170
      term-born infants. Pregnancy-specific anxiety explained 3.3% of the variance of
      attention regulation at 3 months. Perceived stress and pregnancy anxiety taken
      together explained 5% of the variance of attention regulation at 8 months.
      Perceived stress accounted for 8.2% of the variance of difficult behavior of the
      3-month-old infant. All results were adjusted for covariates. CONCLUSIONS:
      Increased maternal prenatal stress seems to be associated with temperamental
      variation of young infants and may be a risk factor for psychopathology later in
      life.

PMID- 12218428
TI  - Assessment of symptom exacerbations in a longitudinal study of children with
      Tourette's syndrome or obsessive-compulsive disorder.
AB  - OBJECTIVES: The severity of tic and obsessive-compulsive (OC) symptoms varies
      over time. Consequently, how do we, as clinicians, know when a change in symptom
      severity occurs that falls outside of the normal range of fluctuation? The goal
      of this study was to describe the level of symptom severity fluctuation over time
      and to establish an objective, prospective, and quantitative method for
      identifying symptom exacerbations in children with Tourette's syndrome, obsessive
      compulsive disorder (OCD), or both. A second major aim was to assess whether
      fluctuations in tic and OC symptom severity covaried with one another. METHOD:
      Monthly consecutive Yale Global Tic Severity Scale and Children's Yale-Brown
      Obsessive Compulsive Scale scores were prospectively obtained in 64 children
      diagnosed with Tourette's syndrome and/or OCD for periods ranging from 3 to 39
      months. Exacerbation thresholds were estimated by using state-of-the-art
      bootstrap methods. These thresholds were then independently evaluated by asking
      two expert clinicians to identify, retrospectively, clinically significant
      exacerbations based on a review of all available clinical and research records.
      RESULTS: The severity of tic and OC symptoms displayed a high degree of
      intrasubject variability. Exacerbation thresholds, which incorporated the change
      score from the previous month and the current symptom score, provided the best
      agreement with those of expert clinicians. When both tic and OC symptoms were
      present, they showed a significant degree of covariation. CONCLUSIONS: Evidence
      based treatments are coming of age. The use of valid, clinician-rated severity
      scales will likely become a standard part of clinical practice. Bootstrapping
      methods may provide a quantitative and convenient way to obtain clinically valid
      thresholds to assess tic and OC symptom exacerbations. This method has the
      potential to be applied to other symptom domains where exacerbation thresholds
      are needed.

PMID- 12218430
TI  - Childhood behavioral profiles leading to adolescent conduct disorder: risk
      trajectories for boys and girls.
AB  - OBJECTIVE: To examine the link between childhood behavioral dimensions and
      adolescent conduct disorder (CD) among a large sample of boys and girls monitored
      longitudinally. METHOD: Teachers rated the behaviors of 1,569 children every year
      between kindergarten and grade 6. On the basis of these seven yearly ratings,
      groups of children who followed distinct trajectories on three behavioral
      dimensions--hyperactivity, fearfulness, and helpfulness--were identified with a
      semiparametric statistical analysis. Children were then categorized into one of
      eight behavioral profiles, representing different combinations of the
      trajectories. Logistic regressions were used to estimate the relation between the
      profiles and CD in adolescence (mean = 15.7 years). RESULTS: Boys had a
      significant risk for CD if they were hyperactive (odds ratio [OR] = 4.27; 95%
      confidence interval [CI], 1.8-10.16); hyperactive and unhelpful (OR = 2.83; CI,
      1.07-7.46); or hyperactive, fearless, and unhelpful (OR = 3.93; CI, 1.27-12.17).
      Girls had a significant risk for CD only if they were both hyperactive and
      unhelpful (OR = 4.61; CI, 1.31-16.24). More boys than girls exhibited profiles of
      risk and met criteria for CD in adolescence. CONCLUSIONS: Sex-specific childhood
      behavioral profiles that represented risk for CD in adolescence were identified.
      There were sex differences in the prevalence of the childhood profiles
      representing risk for CD.

PMID- 12218431
TI  - Influence of adult domestic violence on children's internalizing and
      externalizing problems: an environmentally informative twin study.
AB  - OBJECTIVE: Externalizing and internalizing problems may aggregate in families
      because (1) siblings share genetic risks for problem behaviors or (2) siblings
      are exposed to similar environmental risks. A genetically sensitive design was
      used to determine whether domestic violence accounted significantly for the
      variation and covariation of externalizing and internalizing problems,
      independent of additive genetic effects on these behavior problems. METHOD: Using
      the Achenbach family of instruments, mothers and teachers reported internalizing
      and externalizing problems for 1,116 monozygotic and dizygotic 5-year-old twin
      pairs in the United Kingdom (93% response rate). Mothers reported their
      experiences of domestic violence in the previous 5 years. Structural equation
      models were tested to determine the effect of mothers' experiences of domestic
      violence on children's emotional and conduct problems, controlling for latent
      genetic and environmental effects on these behaviors. RESULTS: A multivariate
      model showed that adult domestic violence accounted for 2% and 5% of the
      variation in children's internalizing and externalizing problems, respectively,
      independent of genetic effects. The co-occurrence of externalizing and
      internalizing scores was accounted for by genetic (62.6%) and shared
      environmental (29.2%) factors and by domestic violence (8%). CONCLUSIONS: Because
      domestic violence affects children's behavior problems beyond genetic influences,
      programs that successfully reduce domestic violence should also prevent
      children's psychopathology.

PMID- 12218432
TI  - Violence exposure, posttraumatic stress disorder, and depressive symptoms among
      recent immigrant schoolchildren.
AB  - OBJECTIVE: Many recent immigrant children are at risk for violence exposure and
      related psychological distress resulting from experiences before, during, and
      after immigration. This study examines the rates of violence exposure and
      associated symptoms among recent immigrant children in Los Angeles. METHOD: 1,004
      recent immigrant schoolchildren (aged 8-15 years) were surveyed about their prior
      exposure to violence and symptoms of posttraumatic stress disorder (PTSD) and
      depression. Participants included children whose native language was Spanish,
      Korean, Russian, or Western Armenian. RESULTS: Participants reported high levels
      of violence exposure, both personal victimization and witnessing violence, in the
      previous year and in their lifetimes. Thirty-two percent of children reported
      PTSD symptoms in the clinical range, and 16% reported depressive symptoms in the
      clinical range. Although boys and older children were more likely to have
      experienced violence, girls reported more PTSD and depressive symptoms. Linear
      multiple regressions revealed that PTSD symptoms were predicted by both recent
      and lifetime violence exposure (p values < .001 and p < .05, respectively), when
      depressive symptoms and gender were controlled. On the other hand, depressive
      symptoms were predicted by recent victimization only (p < .001) when PTSD and
      gender were controlled. CONCLUSION: These findings document the need for
      interventions addressing the psychological sequelae of violence exposure in
      immigrant children.

PMID- 12218433
TI  - Relationship between attachment patterns and personality pathology in
      adolescents.
AB  - OBJECTIVE: To explore the relationship between attachment status and personality
      pathology in a large clinical sample of adolescents. METHOD: Two hundred ninety
      four randomly selected psychiatrists and psychologists were each asked to provide
      data on a patient (aged 14-18 years) in treatment for maladaptive personality
      patterns. Clinicians completed several measures including a clinician-report
      attachment questionnaire, several measures of personality pathology, and a
      clinician-report version of the Child Behavior Checklist. RESULTS: In both
      dimensional and categorical analyses, secure attachment was negatively correlated
      with personality pathology and positively correlated with healthy functioning,
      whereas disorganized/unresolved attachment was strongly associated with multiple
      forms of personality pathology. Anxious/ambivalent attachment tended to be
      associated with measures of withdrawal, internalization, and introversion.
      Avoidant attachment style was not associated with any single form of personality
      pathology. CONCLUSION: The marked association between unresolved attachment and
      more severe psychopathology in adolescents, the lack of construct validity of
      avoidant personality disorder in adolescents, and the broader relations among
      attachment, personality, and psychopathology are discussed.

PMID- 12218434
TI  - Presence and severity of anorexia and bulimia among male and female Omani and non
      Omani adolescents.
AB  - OBJECTIVE: The population of Oman is a heterogeneous mix of nationalities
      providing a natural setting for studying the cross-cultural differences in the
      presence and severity of eating disorders as well as an opportunity for
      evaluating the performance of measurement instruments for these disorders.
      METHOD: Disordered eating screening instruments (the Eating Attitude Test and the
      Bulimic Investigatory Test) were administered to Omani teenagers, non-Omani
      teenagers, and Omani adults. RESULTS: On the Eating Attitude Test, 33% of Omani
      teenagers (29.4% females and 36.4% males) and 9% of non-Omani teenagers (7.5% of
      males and 10.6% females) showed a propensity for anorexic-like behavior. On the
      Bulimic Investigatory Test, 12.3% of Omani teenagers showed a propensity for
      binge eating or bulimia (13.7% females and 10.9% males). Among the non-Omani
      teenagers, 18.4% showed a tendency toward bulimia, with females showing a
      slightly greater tendency than males. In contrast, barely 2% of Omani adults
      showed either a presence of or a severity of disorderly behavior with food.
      CONCLUSION: Omani teenagers scored significantly higher than other ethnic groups
      and Omani adults. This finding is discussed in the light of emerging evidence
      from many parts of the world suggesting that cultural transition, compounded by
      demographic constraints, plays a significant role in abnormal eating attitudes.

PMID- 12218435
TI  - ADHD in Brazil: the DSM-IV criteria in a culturally different population.

PMID- 12218436
TI  - Genetics of childhood disorders: XLII. Autism, part 1: Diagnosis and assessment
      in autistic spectrum disorders.

PMID- 12218438
TI  - Sorting through confusing messages: the art of HAART.

PMID- 12218439
TI  - Once-daily HAART: toward a new treatment paradigm.

PMID- 12218440
TI  - Cardiovascular risk associated with HIV therapy.

PMID- 12218442
TI  - Haemodialysis for the prevention of contrast-induced nephropathy: outcome of 31
      patients with severely impaired renal function, comparison with patients at
      similar risk and review.
AB  - RATIONALE AND OBJECTIVES: To investigate whether haemodialysis prevents contrast
      induced nephropathy (definition: increase of serum-creatinine of >or= 0.5 mg/dL
      within 7 days). MATERIALS AND METHODS: Thirty-one patients (mean serum-creatinine
      4.01 +/- 1.83 mg/dL) were dialyzed for 4.36 +/- 1.0 hours within one hour after
      278.4 +/- 160.5 mL of contrast medium. RESULTS: Dialysis resulted in a
      significant reduction of serum-creatinine (2.25 +/- 1.46 mg/dL; P< 0.0001) and
      stable mean serum-creatinine levels 2, 3, 4, and 7 days after contrast medium and
      at discharge compared with baseline values. However, 19 patients (61%) developed
      contrast-induced nephropathy within 7 days. Four patients had to be repeatedly
      dialyzed. A comparison of our patients' 48 hours-incidence of contrast-induced
      nephropathy (9/31; 29%) versus patients at comparable risk included in seven
      previous studies demonstrated a prophylactic effect of dialysis only versus a
      subgroup in one study. CONCLUSIONS: Data provide no hint that haemodialysis
      prevents contrast-induced nephropathy. Therefore, postprocedural dialysis should
      be restricted to patients participating in clinical studies.

PMID- 12218443
TI  - In vitro characterization of two different ultrasmall iron oxide particles for
      magnetic resonance cell tracking.
AB  - RATIONALE AND OBJECTIVES: Comparison of two different ultrasmall
      superparamagnetic iron oxide (USPIO) particles in terms of their intracellular
      cell-labeling properties of macrophages and subsequent visualization by MR
      imaging. MATERIALS AND METHODS: Cultures containing the macrophage cell line P
      388D1 were incubated with a neutral carboxydextran-coated USPIO preparation (DDM
      43/34/103) or an acidic citrate-coated USPIO (VSOP-C125). Experiments were
      performed in which incubation concentration and duration were varied and
      phagocytosis and pinocytosis suppressed by specific inhibitors. In cell culture
      specimens iron content was measured quantitatively and signal intensities
      determined by in vitro MR imaging. RESULTS: VSOP-C125 is incorporated by cells
      much faster than DDM 43/34/103 and produces significantly higher final
      intracellular iron concentrations per cell (3420 vs. 727 ng/million cells). Both
      preparations show similar signal-reducing effects at MR imaging relative to the
      Fe content per cell. Intracellular USPIO has a much lower detection threshold at
      MR imaging (50/80 micromol/L) than extracellular USPIO in free solution (300
      micromol/L). CONCLUSIONS: Citrate-coated USPIO particles VSOP-C125 appear to have
      more favorable properties for magnetic labeling of macrophages than the
      carboxydextran-coated USPIO preparation DDM 43/34/103.

PMID- 12218444
TI  - 3D versus 2D ultrasound: accuracy of volume measurement in human cadaver kidneys.
AB  - RATIONALE AND OBJECTIVES: Comparison of the accuracy of 3D and 2D ultrasound in
      assessing the volume of human cadaver kidneys. MATERIALS AND METHODS: Before
      autopsy the volume of 22 kidneys was assessed from a 3D data set after manually
      tracing organ contours (3D volumetry) and by applying a 3D ellipsoid formula both
      on a 3D data set and 2D images. Measurements by water-displacement served as the
      gold standard. RESULTS: 3D volumetry showed a mean absolute deviation of 31 mL
      (18.5%) compared with the mean gold standard measurement (168 mL), yielding a
      concordance correlation (Lin's rho(c) ) of 0.71. Calculation based on the
      ellipsoid formula revealed a mean absolute deviation of 37 mL (22.0%) when
      applied on the 3D data set (rho(c) = 0.65) and of 42 mL (25.0%) when applied on
      2D images (rho(c) = 0.61). CONCLUSIONS: 3D volumetry showed a satisfactory
      concordance correlation and is superior to volume calculation based on the
      ellipsoid formula either applied to a 3D data set or to conventional 2D images in
      assessing the volume of human cadaver kidneys.

PMID- 12218445
TI  - Variation of the coronary calcium score depending on image reconstruction
      interval and scoring algorithm.
AB  - RATIONALE AND OBJECTIVES: To evaluate the reconstruction interval dependent
      bandwidth of the coronary calcium score, considering different methods of image
      reconstruction and quantification of coronary calcifications. MATERIALS AND
      METHODS: Seventy-five patients underwent coronary calcium scoring by use of
      retrospectively ECG-gated multislice spiral CT. In all patients overlapping and
      nonoverlapping image reconstruction was performed every 10% of the RR-interval.
      Coronary calcium score was calculated for every reconstructed image series using
      the Agatston score and a volumetric scoring method. In 25 patients the analysis
      was performed twice to determine the reconstruction interval dependent
      intraobserver variability. RESULTS: For nonoverlapping image reconstruction the
      median of the calcium score determined by the Agatston method ranged from 125.8
      to 216.2 and from 166.9 to 211.7 for the volumetric scoring method. For
      overlapping image reconstruction the corresponding values ranged from 91.6 to
      160.5 for the Agatston score and 128.3 to 175.3 for the volumetric calcium score.
      Reconstruction interval dependent median (mean) variation of the coronary calcium
      score ranged from 24.1 (45.5)% for nonoverlapping image reconstruction using the
      Agatston score to 17.5 (25.2)% utilizing a volumetric calcium score with
      overlapping image reconstruction. There was no statistical significant (P< 0.05)
      difference between the different methods. Intraobserver variability for the
      different image reconstruction intervals ranged from 0.78% to 21.51%. The least
      intraobserver variability was found for overlapping image reconstruction during
      the diastole using the volumetric scoring method. CONCLUSIONS: Diastolic image
      reconstruction at 50% or 60% of the RR-interval is recommendable for
      retrospectively ECG-gated multislice spiral CT. Volumetric calcium scoring and
      overlapping image reconstruction are beneficial to reduce the variation of the
      coronary calcium score.

PMID- 12218446
TI  - Comparison of a new recirculation thrombectomy catheter with other devices of the
      same type: in vitro and in vivo evaluations.
AB  - RATIONALE AND OBJECTIVES: To compare a new 7 Fr. Helix thrombectomy catheter with
      Amplatz thrombectomy devices (ATD) with respect to clot fragmentation efficiency,
      hemolytic potential, and risk for vascular trauma. MATERIALS AND METHODS:
      Particle size was evaluated following the maceration of 8-to-10-day-old clots,
      each weighing 6 +/- 0.01 g. The clots were macerated using devices of various
      sizes, including the 7-Fr. Helix thrombectomy catheter, the 7-Fr. over-the-wire
      (OTW), 8-Fr. ATD and the 6-Fr. ATD. The number of particles by weight was
      quantified. The 7-Fr. Helix and the 8-Fr. ATD were tested in the native iliac
      vein of six dogs without presence of clots. Blood samples were obtained before,
      during, and at 1, 3, 6, 24, and 48 hours after the procedure, to monitor the
      hemolytic effects. The treated iliac veins were examined histologically. RESULTS:
      Most of the clot was fragmented into particles <10 microm. The mean percentage by
      weight of the original clot that remained as particles larger than 10 microm was
      1.59% in the 7-Fr. Helix group. This was significantly less than 3.10% with the 6
      Fr. ATD, 2.57% with 7-Fr. OTW and 2.44% in the 8-Fr. ATD group (<0.01). In vivo
      results showed a higher plasma free hemoglobin (PFH) level starting 5 minutes
      after initiating the ATD activation, reaching its peak after completion of the
      activation, and declining afterward, with return to the baseline at 24 hours. The
      haptoglobin level tended to decline slightly at 10 minutes, reaching its lowest
      level at 24 hours, and starting to recover at 48 hours. A similar pattern of PFH
      and haptoglobin changes was found in both groups. There were no significant
      differences regarding hemolytic effect of the two tested devices. No significant
      changes of creatinine were observed for up to 48 hours after procedures. Focal
      microthrombosis was seen in two sites of two vessels treated with the 7-Fr. Helix
      and a focal injury of a venous valve was noted in the 8-Fr. ATD group. The media
      and internal elastic lamina (IEL) were intact in all cases. CONCLUSION: The newly
      designed 7-Fr. Helix is more effective in fragmentation in vitro clots than the 6
      Fr. ATD, 7-Fr. OTW and the 8-Fr. ATD. The 7-Fr. Helix and the 8-Fr. ATD produced
      hemolytic effects, but they appeared to be tolerated by the animals. The in vivo
      results indicated that the 7-Fr. Helix appears to be as safe as the 8-Fr. ATD.

PMID- 12218447
TI  - Capillary embolization using ethiodol-ethanol for complete renal ablation in
      Swine.
AB  - RATIONALE AND OBJECTIVES: To evaluate the effect of capillary embolization with
      superselectively administered 1:1 Ethiodol-ethanol mixture (EEM) for complete
      nephrectomy in normal porcine kidneys. MATERIALS AND METHODS: One kidney in each
      animal was completely embolized by sequential segmental arterial injections of
      the EEM via a microcatheter until complete capillary stasis occurred. Group 1 (n
      = 5): Initial embolization did not occlude the arterial compartment. Group 2 (n =
      7): The capillary embolization was performed in conjunction with absolute ethanol
      injection and coil placement during balloon catheter occlusion. RESULTS: Group 1:
      Complete recanalization occurred following the EEM embolization (1-week). After
      the repeat embolization (EEM + pure ethanol without balloon occlusion), three of
      five kidneys showed partial recanalization (2-weeks). Following a third
      embolization (EEM + coil) in two pigs, one kidney showed partial recanalization
      (12-weeks). Group 2: Complete renal artery occlusion was achieved in all kidneys
      with no recanalization. Histologically, four kidneys exhibited total ablation
      whereas three showed minimal preexisting parenchyma (8-weeks). CONCLUSIONS:
      Permanent arterial occlusion with histologically complete renal ablation was
      achieved using a two-phase technique of homogeneous capillary embolization with
      1:1 EEM and ethanol and coil occlusion performed during temporary balloon
      occlusion. Sequential segmental EEM injections alone did not produce permanent
      capillary embolization.

PMID- 12218448
TI  - Bone injury associated with anterior cruciate ligament and meniscal tears:
      assessment with bone single photon emission computed tomography.
AB  - RATIONALE AND OBJECTIVES: Acute injury of the menisci and ligaments about the
      knee joint is often associated with accompanying bone injury. The role of bone
      single photon emission computed tomography (SPECT) was assessed in this clinical
      setting. MATERIALS AND METHODS: Knee SPECT was performed in 94 patients with
      suspected ACL, meniscal tear, or both and was correlated with arthroscopy (n =
      74), magnetic resonance imaging (MRI) (n = 37), or both. Scintigraphic findings
      were categorized based on their anatomic location and on uptake intensity (0-3
      grade scale). RESULTS: Correlation with arthroscopy: Eleven patients had a normal
      arthroscopy of which in 10, SPECT images detected no abnormality. Sixty-three
      patients had abnormal arthroscopic findings, whereas all had abnormal SPECT
      studies. Thirty-eight patients had an anterior cruciate ligament (ACL) tear on
      arthroscopy. In this type of injury SPECT images detected increased uptake in the
      posterior aspect of the lateral tibial plateau (LTPp) with a positive predictive
      value (PPV) of 93% and a negative predictive value (NPV) of 97%. In 55% of the
      patients, increased uptake was also detected in the region of the middle sulcus
      of the lateral femoral condyle (LFCm): a "kissing" pattern. Tear of the medial
      meniscus was diagnosed by arthroscopy in 43 patients. SPECT images detected
      increased uptake in the medial tibial plateau (MTP) with a PPV of 78% and a NPV
      of 83%. Correlation with MRI: all seven cortical fractures seen on MRI were
      detected on SPECT. Twenty-eight patients had MRI findings suggestive of an ACL
      injury. Accompanying bone bruises were seen in 18 of them (64%). On SPECT images,
      all 28 patients with an ACL tear had increased uptake in the LTPp. Intensity of
      uptake in patients with associated bone bruise, however, was significantly
      higher; mean intensity grade 2.4 +/- 0.7 in case of accompanying bone bruise
      compared with 1.4 +/- 0.8 in case of an ACL tear without associated bone injury,
      P< 0.01. CONCLUSION: Results of the study suggest that bone SPECT is valuable in
      acute knee trauma for assessment of ACL, meniscal tears, or both and for
      detection of associated bone injury.

PMID- 12218449
TI  - 3D modeling and virtual endoscopy of the small bowel based on magnetic resonance
      imaging in patients with inflammatory bowel disease.
AB  - RATIONALE AND OBJECTIVES: Small bowel MRI (MR imaging) is a new imaging modality
      that excellently depicts small intestine pathology in patients with inflammatory
      bowel disease. Virtual endoscopy based on sectional imaging is a recently
      introduced technique to create endoscopy like views. The aim of this study was to
      evaluate the feasibility of virtual small bowel endoscopy based on MR imaging in
      patients with Crohn disease. MATERIALS AND METHODS: Thirty consecutive patients
      with Crohn disease were scanned after oral application of pineapple juice for
      contrasting the small bowel. Dedicated high resolution T1 weighted 3D-FLASH
      sequences with fat suppression were used for volume scanning. Volume-rendered 3D
      models of the small bowel were created and virtual endoscopy was performed. The
      feasibility and quality of this new visualization method was assessed. RESULTS:
      In nine of 30 patients virtual endoscopy was considered as good quality (flight
      through the entire small bowel was possible, typical folds were revealed). In 18
      patients fair quality (at least 4/5 of the small bowel were depicted adequately)
      was assessed. In three of 30 patients virtual endoscopy was not sufficiently
      possible because of inadequate bowel filling or breathing artifacts. Three
      fistulae diagnosed on 2D MRI were visualized on the virtual endoscopic view.
      CONCLUSION: Virtual endoscopy of the small bowel is feasible based on high
      resolution MR imaging. Vivid insight views and 3D models provide an interesting
      addition to sectional MR findings.

PMID- 12218450
TI  - Recurrent genomic aberrations in gastric carcinomas associated with Helicobacter
      pylori and Epstein-Barr virus.
AB  - Helicobacter pylori and Epstein-Barr virus (EBV) both have been associated with
      gastric carcinoma. No specific genomic aberrations have been reported in
      association with these agents. We studied 20 cases of primary gastric carcinoma
      (including 11 positive for and 6 for EBV) by comparative genomic hybridization
      with validation of results by fluorescence in situ hybridization, loss of
      heterozygosity analysis, and immunohistochemistry. The results were analyzed in
      respect to presence or absence of and EBV. The tumors were also compared in terms
      of histologic type, tumor location, and lymph node metastases. The most
      frequently observed aberrations in the gastric carcinomas were gains of
      chromosome 19, 17, 1p, 11, 20q, and 22. The more common losses were found in 4q,
      6q, 13q, and 15q. Gains in chromosome 19 and losses in 9p23-pter were found more
      commonly in cases with (P < 0.05). Gains in centromeric region of chromosome 19
      were more common in the EBV-negative cases (P < 0.05). Immunohistochemical
      expression of and correlated with gains in the regions containing these genes.
      Gains in chromosome 11 and losses in 15q15 were more common in cases with EBV (P
      < 0.01 and P < 0.001, respectively). There was no significant association between
      any genomic aberration and histologic type, tumor location, or nodal metastases.
      and EBV are associated with different genomic imbalances, suggesting that these
      infectious agents exert different influences in the development of gastric
      carcinoma.

PMID- 12218452
TI  - Histologic distribution of fatal rotaviral pneumonitis: an immunohistochemical
      and RT in situ PCR analysis.
AB  - Rotaviral infection is a common cause of gastroenteritis and pharyngitis; to our
      knowledge, infection has not been associated with severe pneumonia. We report on
      two cases of fatal pneumonitis in 49-and 54-year-old men; the latter was on long
      term steroid treatment of multiple sclerosis. In the latter case, the histologic
      examination after a several week history of symptoms showed severe organizing
      interstitital pneumonitis and necrotizing bronchiolitis with extensive squamous
      metaplasia. The other case, which was fatal several days after the onset of
      symptoms, showed marked septal capillaritis with denudement of the alveolar
      pneumocytes, extravascated red blood cells, and intravascular thrombi formation.
      In each case, rotaviral RNA was localized by reverse transcription (RT) in situ
      PCR to the endothelial cells of the alveolar capillaries, macrophages, and
      pneumocytes as well as, in the second case, to the squamous metaplastic cells.
      Immunohistochemical analysis for the virus demonstrated an equivalent histologic
      distribution. It is concluded that rotaviral infection can lead to fatal
      pneumonitis and that the mechanism of this complication is centered on a diffuse
      septal endothelialitis with concomitant tissue damage.

PMID- 12218451
TI  - Changes of interleukin expression correlate with Helicobacter pylori infection
      and lymph node metastases in gastric carcinoma.
AB  - Helicobacter pylori (HP) infection induces expression of IL-8 and IL-10 in benign
      gastric epithelium. This study compared the expression of cytokines in CD4+ and
      CD8+ lymphocyte subsets of peripheral blood lymphocytes (PBL), benign mucosal
      lymphocytes (ML), and tumor infiltrative lymphocytes (TIL) as well as in the
      benign and malignant epithelial cells of the same patient, with respect to the
      presence of HP infection, lymph node metastases, and tumor histologic type. The
      mRNA of the cytokines was measured by a semiquantitative RT-PCR method. The
      levels were ranked and compared using the Wilcoxon sign-ranked test. Compared
      with CD8+ ML, the CD8+ TIL expresses higher levels of IL-6 and IL-8 but lower
      level of IL-4 in patients with lymph node metastases. In patients with HP
      infection, expression of IL-8 and IL-10 was higher in the gastric carcinoma cells
      than in the benign epithelial cells while expression of IL-6 and IL-8 were higher
      in CD8+ TIL than CD8+ ML. Overexpression of IL-8 in HP associated gastric
      carcinomas suggested that they might have arisen from HP-infected epithelial
      cells.

PMID- 12218453
TI  - Demonstration of human herpesvirus 8 in a case of primary vaginal epithelioid
      angiosarcoma by in situ hybridization, electron microscopy, and polymerase chain
      reaction.
AB  - We demonstrate the presence of human herpesvirsus 8 (HHV-8) in a primary vaginal
      location of angiosarcoma (AS) by polymerase chain reaction (PCR), in situ
      hybridization, and ultrastructural direct visualization of viral particles. The
      latter two techniques for the first time confirm HHV-8 detection in an AS by PCR;
      these results contribute to the debate caused by the controversial data produced
      by the almost exclusive use of PCR for investigating the possible presence of HHV
      8 in AS, and its possible implications. Moreover, the investigated AS is the
      seventh published primary vaginal one, and the fourth unrelated to radiotherapy.
      Interestingly, the affected patient had used a ring pessary for 10 years because
      of an uterovaginal prolapse.

PMID- 12218454
TI  - Detection of a novel point mutation of the prothrombin gene at position 20209.
AB  - Detection of the prothrombin G20210A mutation was performed on the LightCycler
      Instrument (Roche Molecular Biochemicals, Mannheim, Germany) using commercially
      available primers and hybridization probes. Herein we report four cases from
      unrelated African American individuals where LightCycler analysis showed atypical
      melting curves. Sequence analysis of the four samples showed heterozygosity for a
      C to T mutation 1 bp upstream from the known 20210 mutation at position 20209.
      The clinical significance of this mutation is not known, but three patients in
      whom it was detected had a history of venous thrombosis or stroke. The fourth
      patient had severe liver disease, which may have masked thrombotic
      predisposition. Since most assays used to detect the G20210A mutation use a
      PCR/restriction digestion assay, which would not detect the C20209T mutation,
      this new mutation may be underrecognized when prothrombin gene mutation testing
      is performed by PCR/restriction digestion assay.

PMID- 12218455
TI  - Fusion of the FUS and ATF1 genes in a large, deep-seated angiomatoid fibrous
      histiocytoma.
AB  - We report a case of a large, deep-seated, diagnostically difficult angiomatoid
      fibrous histiocytoma. The neoplastic cells were positive for vimentin, calponin,
      CD99, and, focally, for desmin and contained intertwining cytoplasmic processes
      joined by desmosomelike junctions. Fusion of codon 175 of the gene to codon 110
      of the gene was detected by reverse transcription-polymerase chain reaction.
      Because identical fusion of the and genes has been recently reported in another
      case of angiomatoid fibrous histiocytoma, fusion of these genes may be
      characteristic for at least a subset of these tumors.

PMID- 12218456
TI  - P16INK4A and p15INK4B gene alteration associated with oxidative stress in renal
      cell carcinomas after the chernobyl accident (pilot study).
AB  - Our study was undertaken to better understand the role of G1/S transition
      abnormalities in the malignant progression of renal cell carcinomas (RCCs),
      exposed to long-term low doses of ionizing radiation (IR), from patients living
      in radiocontaminated areas of the Ukraine after the Chernobyl accident. We
      studied p16 and p15 gene alteration in association with oxidative stress markers,
      including inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). We
      analyzed 88 samples collected from 22 patients with RCCs and with different
      exposure to IR. Homozygous deletion of the p16 and p15 genes, as well as
      hypermethylation of the 5CpG island in the promoter region of the same genes,
      were analyzed by differential PCR and Methylation-Specific PCR respectively, in
      association with histopathology and immunohistochemical analysis of p16 and p15
      proteins. COX2 and iNOS expression in the same tumors were likewise analyzed.
      Aberrant hypermethylation was observed in 7 (32%) and 5 (23%) cases accompanied,
      by immunohistochemical loss of expression for p16 and p15 genes respectively, in
      both high stage and grade tumors from patients living in radiocontaminated areas,
      this being especially outstanding for the p16 gene. An association with COX2 and
      less iNOS overexpression in the same tumors was observed. Our data suggest that
      inactivation of p16 gene, but not p15, induced by increased oxidative stress
      generated by persistent chronic exposure to IR, could be one of the major
      pathways responsible for RCCs malignant progression.

PMID- 12218457
TI  - Postmortem RNA and protein stability in perinatal human lungs.
AB  - The availability of fetal and neonatal lung tissue is an invaluable resource to
      elucidate the molecular regulation of human lung development. In this study, we
      have investigated the mRNA and protein stability of perinatal lung tissues
      treated with RNA (Ambion Inc., Austin, TX) or snap frozen in liquid nitrogen (LN
      ). Lung samples were obtained from 25 consecutive perinatal autopsies of live
      born and stillborn infants (median gestational age, 23 weeks) with various
      clinical presentations. Treatment of lung tissue with RNA yielded more total RNA
      and protein than LN freezing. The integrity of RNA, assessed by spectrophotometry
      and gel electrophoresis, was equivalent between both tissue preservation methods,
      and both methods produced RNA suitable for reverse transcriptase-polymerase chain
      reaction analysis of representative genes (beta-actin and surfactant protein-B
      [SP-B]). Similarly, the protein integrity of RNA -treated tissues was equivalent
      to that of LN -frozen tissues, as judged by Western blot analysis of SP-B/actin
      protein expression. Although the total yield was similar in live-born,
      nonmacerated stillborn and macerated stillborn infants, only RNA and protein from
      live-born or nonmacerated stillborn infants was suitable for subsequent molecular
      analyses. Within the 41-hour range studied, the duration of the postmortem
      interval did not affect the yield or integrity of RNA and protein with either
      tissue preservation method. In summary, high-quality RNA and protein, suitable
      for routine molecular analyses, can be obtained from postmortem lung tissue from
      live-born and nonmacerated stillborn infants, even with prolonged postmortem
      intervals. RNA is equivalent, if not superior, to LN for preservation of
      postmortem RNA and protein in developing human lungs.

PMID- 12218458
TI  - Real-time quantitative analysis of telomerase activity in breast tumor specimens
      using a highly specific and sensitive fluorescent-based assay.
AB  - Telomerase activity has been associated with almost 90% of malignant human
      cancers from a variety of tissue sources, making it one of the most prominent
      molecular cancer markers known to date. As such, telomerase has become a very
      attractive diagnostic and therapeutic target. The advent of the telomeric repeat
      amplification protocol (TRAP) has allowed for the semiquantitative detection of
      telomerase from limiting sample amounts. Both the standard TRAP assay and a real
      time assay using Amplifluor technology with primers designed specifically for
      telomerase activity amplification were used to quantitatively assess telomerase
      activity in primary tumors and tumor-derived cell lines. We have adapted the
      recently developed TRAPeze XL telomerase detection kit (Intergen, Gaithersburg,
      MD) for use with real-time polymerase chain reaction for more accurate
      quantification and high-throughput capabilities. In doing so, the reliability,
      assay time, and accuracy of quantitation have all been dramatically improved. A
      comparison of the quantitative analysis for the standard TRAP assay versus the
      real-time assay using 19 breast tumors revealed telomerase quantitation and
      standardization using the real-time assay was superior to the standard assay. Our
      data suggest that this assay will be useful for clinical and research studies
      involving detection of telomerase activity as it relates to cancer diagnosis.

PMID- 12218459
TI  - Oculoplastic and orbital surgery.

PMID- 12218460
TI  - Enucleation versus evisceration.
AB  - Removal of the eye may be necessary after severe ocular trauma, to control pain
      in a blind eye, to treat some intraocular malignancies, in endophthalmitis
      unresponsive to medical therapy, and for cosmetic improvement of a disfigured
      eye. The choice of procedure to accomplish this is best made by an informed
      patient. Enucleation and evisceration can each achieve the desired goals, but
      several factors must be considered in choosing the most appropriate procedure.

PMID- 12218461
TI  - Obstruction of the lacrimal drainage system.
AB  - This review covers evolving concepts in lacrimal outflow obstruction. Recent
      studies have increased our understanding of the surgical anatomy and
      pathophysiology of the lacrimal drainage system through radiologic, clinical, and
      microbiologic techniques. While external dacryocystorhinostomy remains an
      important treatment for nasolacrimal duct obstruction, there have been a number
      of therapeutic developments worthy of review, including advances in endoscopic
      and transcanalicular dacryocystorhinostomy, conjunctivodacryocystorhinostomy, and
      the use of mitomycin C in these procedures. In addition, we summarize recent
      advances in minimally invasive techniques for lacrimal outflow obstruction,
      including balloon dacryocystoplasty, lacrimal stents, and conjunctivoplasty.
      Finally, the roles of probing versus irrigation, nasal endoscopy, and endoscopic
      dacryocystorhinostomy in children are discussed.

PMID- 12218462
TI  - Orbital decompression: current concepts.
AB  - The orbit in Graves disease undergoes expansion in soft tissue content as a
      result of the infiltration of orbital fat, extraocular muscles, and the lacrimal
      gland. Compression of the intraorbital contents leads to disorders of the lid
      corneal interface, keratopathy, motility disturbances, exophthalmos, and optic
      neuropathy. Orbital decompression has traditionally been reserved for those
      patients with unremitting optic neuropathy. This article provides a historical
      review of orbital decompression, as well as a review of the evolution of surgical
      approaches toward both soft tissue and bony decompression. Recent trends in
      surgical management include fat decompression, more extensive posterior sculpting
      of the lateral wall, and direct approaches to the medial wall. Preoperative
      predictors of diplopia and hypoglobus are addressed, as are the various
      techniques that are employed to limit new postoperative strabismus. The roles of
      endoscopy and combined surgical techniques are also reviewed. Expanded
      indications for decompression and its effect on increased intraocular pressure
      are discussed as well.

PMID- 12218463
TI  - Sentinel node biopsy as a tool for accurate staging of eyelid and conjunctival
      malignancies.
AB  - Sentinel lymph node (SLN) biopsy has emerged as a technique for accurate staging
      of solid tumors. This technique permits the detection of microscopic metastases
      in clinically negative regional lymph nodes and may be indicated for malignancies
      that have a propensity for regional nodal metastasis. With the exception of basal
      cell carcinoma, almost all malignancies of the eyelid and conjunctiva metastasize
      to regional lymph nodes as the site of first metastasis. The histologic status of
      the SLNs has been shown to be the most significant prognostic factor with respect
      to recurrence and survival in patients with cutaneous melanoma. The indications
      for and the feasibility of SLN biopsy for eyelid and conjunctival tumors and our
      experience with this technique are reviewed.

PMID- 12218464
TI  - Advances in cosmetic oculoplastic surgery.
AB  - According to the American Society for Aesthetic Plastic Surgery, in the year 2000
      over 5.7 million cosmetic surgical and nonsurgical procedures were performed in
      the United States. This was a 25% increase above the total number performed in
      1999. The most popular of these procedures was botulinum toxin injection,
      followed by chemical peels and microdermabrasion. As the field of plastic and
      reconstructive surgery changes, so does the scope of the oculoplastic surgeon.
      This review article summarizes those developments in aesthetic surgery that are
      recent additions to the practice of aesthetic oculoplastic surgery. It highlights
      the most recent literature discussing brow and midface lifts, skin lasers,
      microdermabrasion, upper and lower blepharoplasty, chemical peels, botulinum
      toxin, and fat sculpturing.

PMID- 12218465
TI  - Current treatment of retinoblastoma.
AB  - Chemotherapy has recently achieved a major role in the primary management of
      intraocular retinoblastoma. Tumor reduction by first-line chemotherapy
      (chemoreduction) followed by local treatments is now accepted as treatment
      strategy for intraocular retinoblastoma with the goal of avoiding external beam
      radiotherapy (EBRT) or enucleation. Although efficient in reducing tumor volume,
      chemotherapy cannot cure retinoblastoma. Different chemoreduction protocols are
      used to shrink the tumor, making it treatable with cryotherapy, laser
      photocoagulation, thermotherapy, and plaque radiotherapy. Systemic chemotherapy
      used with local ophthalmic therapies during or after the chemotherapy can
      eliminate the need for enucleation or external beam radiotherapy in Reese
      Ellsworth group 1, 2, or 3 retinoblastoma. This combination is not sufficient to
      obtain tumor control in most eyes with large tumors and diffuse vitreous and
      subretinal seeds (Reese-Ellsworth group 4 and 5 tumors), and EBRT or enucleation
      is eventually required. The resultant visual acuity after globe-conserving
      therapies in those eyes with Reese-Ellsworth group 4 and 5 tumors is often poor.
      Preliminary results of a phase I/II study of subconjunctival carboplatin
      injection are encouraging. Enucleation is still recommended in situations such as
      eyes containing large tumors, long standing retinal detachment, neovascular
      glaucoma, pars plana tumor seeding, anterior chamber involvement or choroid,
      optic nerve or orbital tumor extension, and no expectation for useful vision.
      Chemoprophylaxis is necessary for patients with tumor extending to the surgical
      margin of the optic nerve and is likely beneficial in preventing metastases in
      patients with tumor extending beyond the lamina cribrosa. Intensified
      chemotherapy with autologous stem cell rescue appears effective for patients with
      metastatic retinoblastoma.

PMID- 12218466
TI  - Clinical research in pediatric ophthalmology: the Pediatric Eye Disease
      Investigator Group.
AB  - The Pediatric Eye Disease Investigator Group (PEDIG) is a network of university
      based and community-based pediatric eye care practitioners that is conducting
      multiple clinical research studies. The group has conducted the Congenital
      Esotropia Observational Study, which assessed the early course of esotropia in
      infants, and the Amblyopia Treatment Studies, a series of randomized trials, the
      first of which compared atropine and patching for treatment of moderate amblyopia
      in children 3 to <7 years old. Herein, the results of these studies are
      summarized, and the current and future studies of the group are described.

PMID- 12218468
TI  - Introduction. Treatment of injuries to athletes. 1962.

PMID- 12218469
TI  - The science of anterior cruciate ligament rehabilitation.
AB  - This review of the literature assessed what is known about the biomechanics of
      the normal anterior cruciate ligament during rehabilitation exercises, the
      biomechanical behavior of the anterior cruciate ligament graft during healing,
      and clinical studies of rehabilitation after anterior cruciate ligament
      replacement. After anterior cruciate replacement, immobilization of the knee, or
      restricted motion without muscle contraction, leads to undesired outcomes for the
      ligamentous, articular, and muscular structures that surround the joint. It is
      clear that rehabilitation that incorporates early joint motion is beneficial for
      reducing pain, minimizing capsular contractions, decreasing scar formation that
      can limit joint motion, and is beneficial for articular cartilage. There is
      evidence derived from randomized controlled trials that immediately after
      anterior cruciate ligament reconstruction, weightbearing is possible without
      producing an increase of anterior knee laxity and is beneficial because it lowers
      the incidence of patellofemoral pain. Rehabilitation with a closed kinetic chain
      program results in anteroposterior knee laxity values that are closer to normal,
      and earlier return to normal daily activities, compared with rehabilitation with
      an open kinetic chain program. This review revealed that more randomized,
      controlled trials of rehabilitation are needed. These should include the
      clinicians' and patients' perspective of the outcome, and biomarkers of articular
      cartilage metabolism.

PMID- 12218470
TI  - Articular cartilage injuries.
AB  - The acute and repetitive impact and torsional joint loading that occurs during
      participation in sports can damage articular surfaces causing pain, joint
      dysfunction, and effusions. In some instances, this articular surface damage
      leads to progressive joint degeneration. Three classes of chondral and
      osteochondral injuries can be identified based on the type of tissue damage and
      the repair response: (1) damage to the joint surface that does not cause visible
      mechanical disruption of the articular surface, but does cause chondral damage
      and may cause subchondral bone injury; (2) mechanical disruption of the articular
      surface limited to articular cartilage; and (3) mechanical disruption of
      articular cartilage and subchondral bone. In most instances, joints can repair
      damage that does not disrupt the articular surface if they are protected from
      additional injury. Mechanical disruption of articular cartilage stimulates
      chondrocyte synthetic activity, but it rarely results in repair of the injury.
      Disruption of subchondral bone stimulates chondral and bony repair, but it rarely
      restores an articular surface that duplicates the biologic and mechanical
      properties of normal articular cartilage. In selected patients, surgeons have
      used operative treatments including penetrating subchondral bone, soft tissue
      grafts, and cell transplants and osteochondral autografts and allografts to
      restore articular surfaces after chondral injuries. Experimental studies indicate
      that use of artificial matrices and growth factors also may promote formation of
      a new joint surface. However, an operative treatment of an articular surface
      injury that will benefit patients must not just provide a new joint surface, it
      must produce better long-term joint function than would be expected if the injury
      was left untreated or treated by irrigation and debridement alone. Therefore,
      before selecting a treatment for a patient with an articular cartilage injury,
      the surgeon should define the type of injury and understand its likely natural
      history.

PMID- 12218471
TI  - Techniques of medial retinacular repair and reconstruction.
AB  - Insufficiency of the passive patellar restraints results in lateral patellar
      instability by allowing excessive lateral displacement of the patella. Although
      the surgical approach to patellar instability traditionally has been to realign
      the dynamic elements (muscle forces) that pull the patella laterally, newer
      techniques have sought to restore the integrity of key medial passive
      (ligamentous) stabilizers. An increasing body of evidence indicates that the
      chief medial ligamentous restraint is the medial patellofemoral ligament. The
      current authors examine the principles of medial retinacular repair and
      reconstruction as they relate to patellar stability. Individual techniques and
      approaches are discussed, including primary repair with or without augmentation,
      and reconstruction using autogenous tendon, allografts, and synthetic graft
      materials. These procedures share the common objective of addressing the
      essential lesion in lateral patellar instability to restore the normal passive
      restraints against lateral patellar displacement.

PMID- 12218472
TI  - Anterior cruciate ligament reconstruction with patellar autograft tendon.
AB  - There are many techniques, graft choices, and outcome studies evaluating anterior
      cruciate ligament reconstruction. The current authors specifically look at
      reconstruction with the patellar tendon from a scientific perspective. Miniopen,
      endoscopic, and two-incision operative techniques in addition to hamstring versus
      patellar tendon autograft reconstructions are compared via randomized prospective
      studies. A review of all studies evaluating arthroscopically-assisted anterior
      cruciate ligament reconstruction with patellar tendon was conducted. The authors
      found arthroscopically-assisted anterior cruciate ligament reconstruction to have
      a high short-term stability rate, extremely high patient satisfaction level, and
      a low postoperative complication rate. When the endoscopic technique was compared
      with the two-incision technique, there were no major differences. The difference
      between patellar tendon and hamstring autograft reconstruction can be described
      best as subtle, except for the consistent finding of an increased activity level
      in the patellar tendon group. When the principles of anterior cruciate
      reconstruction are followed, one can expect consistent results with patellar
      tendon autograft reconstruction.

PMID- 12218473
TI  - Anterior cruciate ligament reconstruction using hamstring tendon grafts.
AB  - The annual incidence of more than 100,000 anterior cruciate ligament tears has
      increased with the rise of participation in sports in the general population,
      especially in females and older participants. Anterior cruciate ligament
      reconstruction is the standard of care in the young and/or athletically active
      individuals, based on prospective randomized studies. Replacement tissues to
      reconstruct the anterior cruciate ligament can be categorized as autograft,
      allograft, xenograft, and artificial replacements. Historically, xenograft and
      artificial replacements for the anterior cruciate ligament have failed dismally.
      As a result, autograft and allograft tissues commonly are used to reconstruct the
      anterior cruciate ligament. Autograft tissue currently is the most common source
      for grafts used worldwide. The two most common autograft tissues are the bone
      patellar tendon-bone and hamstrings tendons. Controversy exists regarding the
      advantages and disadvantages of using each of these two tissues. The purpose of
      the current study was to review the basic science and clinical data regarding the
      use of the hamstring tendons in anterior cruciate ligament reconstruction.

PMID- 12218474
TI  - Strategies for enhancing proprioception and neuromuscular control of the knee.
AB  - Proprioception and neuromuscular control of the knee are compromised after
      ligament injury and must be regained if the athlete is to return to high level
      sports at a normal injury risk level. The anterior cruciate ligament deficient
      and reconstructed knee will be used as a model to describe differences in
      proprioception and neuromuscular control to those of an uninjured knee. The
      purpose of the current review is threefold. First, the basic science of
      proprioception and neuromuscular control specific to the knee will be summarized
      and reviewed. The review will include an overview of terminology,
      neurophysiology, and the effects of injury on the function of both lower limbs.
      Second, tools used for assessment and rehabilitation of proprioceptive deficits
      will be evaluated. Specific rehabilitation procedures that incorporate
      prophylactic conditioning that focus on transitioning the injured athlete back
      into sport will be presented. Finally, the literature with respect to gender
      variation in proprioception and neuromuscular control will be evaluated. The goal
      of the current review is to provide the clinician and the clinical scientist with
      sufficient background information for the development of quantitative methods to
      evaluate a patient's functional capacity and to assist in preventative,
      preoperative, and postoperative decision-making strategies.

PMID- 12218475
TI  - Development and validation of health-related quality of life measures for the
      knee.
AB  - Health-related quality of life is an individual's perception of his or her health
      and it is an important outcome measure for clinical research in orthopaedics. For
      clinical outcomes research related to the knee, measures of health-related
      quality of life should consider disability imposed by impairment of the knee.
      Health-related quality of life is measured by assembling questions to represent
      the construct of health-related quality of life. Validation of health-related
      quality of life requires evidence to support the interpretation and usefulness of
      the resulting score. The purpose of the current paper was to provide readers with
      a framework for identifying and selecting relevant clinical outcome measures that
      should be considered when designing clinical research related to the knee. The
      need to include reliable, valid, and responsive measures of health-related
      quality of life in clinical outcomes research related to the knee was discussed
      and the process for developing such measures was shown by describing the process
      used to develop the International Knee Documentation Committee Subjective Knee
      Form.

PMID- 12218476
TI  - Diagnosis and treatment of posterolateral knee injuries.
AB  - Posterolateral knee injuries can be very debilitating. It is important to
      understand the complex anatomy and pertinent diagnostic tests to properly treat
      posterolateral knee injuries. The fibular collateral ligament, popliteus tendon,
      and the popliteofibular ligament are the main static stabilizers against abnormal
      varus and posterolateral translational moments. Important radiographic imaging
      studies for the posterolateral knee include full length anteroposterior
      radiographs, taken with the patient standing, to assess for varus alignment in
      patients with chronic injuries and high field (1.5 tesla or higher) magnetic
      resonance imaging with specific posterolateral knee sectioning. A physical
      examination that includes the external rotation recurvation test, varus stress
      test at 30 degrees, dial test at 30 degrees and 90 degrees, posterolateral drawer
      test, reverse pivot shift, and an assessment for a varus thrust gait are
      essential to properly diagnose a posterolateral knee injury. Patients with acute
      (< 3 weeks) anatomic repairs of Grade III posterolateral knee injuries have the
      best functional outcome. Although various surgical reconstruction techniques have
      been developed to treat chronic or irreparable acute posterolateral knee
      injuries, these techniques have not achieved outcomes comparable with the
      treatment of other ligament injuries of the knee. Techniques for anatomic
      reconstructions of these structures are just being developed. Improved education
      of clinicians as to the proper diagnosis of posterolateral knee injuries is
      necessary because a large number of these injuries still are missed on initial
      examinations. In addition, additional research into the most optimal
      posterolateral knee reconstruction techniques and outcome studies are needed to
      improve the treatment of this debilitating knee injury.

PMID- 12218477
TI  - Meniscus repair: considerations in treatment and update of clinical results.
AB  - The meniscus plays an important role in the function of the knee. Preservation of
      the meniscus is preferred if possible when considering treatment of a meniscus
      tear. A thorough understanding of the anatomy of the meniscus, the structure, the
      mechanics, and other factors of meniscal healing are critical when evaluating the
      torn meniscus for a reparative procedure. Many options for meniscus repair exist
      for the orthopaedist. Options such as open repair or arthroscopically-assisted
      inside-out techniques have long-term favorable results. The all-inside techniques
      are attractive because of the decrease in operative time and ease of the
      technique. Short-term results are positive for the all-inside technique; however,
      good long-term data on these techniques are lacking. Few well-designed
      prospective studies exist on any of the meniscus repair techniques. Future
      directions include the potential use of growth factors and gene therapy to
      augment meniscus repair.

PMID- 12218478
TI  - Soft tissue allografts for knee reconstruction in sports medicine.
AB  - Soft tissue allografts are an important substitute tissue for the reconstruction
      of deficient ligaments, torn menisci, and osteochondral defects during knee
      surgery. Interest in allografts for soft tissue reconstruction has arisen from
      the demand to obtain a stable knee with restoration of function and protection
      against additional injury. Use of allografts for soft tissue reconstruction is
      associated with less donor tissue site morbidity and reduced surgical time.
      Nevertheless, use of allografts has a potential for disease transmission, delayed
      graft incorporation, and host versus donor immunologic response to the graft.
      Experimental studies and animal models have provided information about the
      biologic aspects of graft incorporation and remodeling and have contributed to
      the development of methods of graft preparation and transplantation. Clinical
      studies of allograft transplantation in humans have helped to define surgical
      indications and techniques and have allowed for the assessment of clinical
      outcome. The current authors review the current literature concerning the basic
      and clinical principles of soft tissue allografts for knee reconstruction, and
      underscore the scientific basis for the clinical application of allograft tissue
      during knee surgery.

PMID- 12218479
TI  - Long-term survival of McKee-Farrar total hip prostheses.
AB  - Because of the recent resurgence of interest in metal-on-metal bearing components
      for total hip arthroplasties, the long-term results of 153 consecutive McKee
      Farrar total hip arthroplasties done in 129 patients by one surgeon between 1969
      and 1973 were evaluated. A retrospective chart review provided patient
      demographics (age, gender, weight, primary diagnosis), revision dates,
      indications, and implant survival data. The average age of the patients at
      implantation surgery was 61 years (range, 28-85 years) and these patients were
      observed as many as 28 years. Primary diagnoses included osteoarthritis (49% of
      implants), rheumatoid arthritis (38%), and other conditions (13%). During the 28
      years of followup, five implants were revised for infection and 14 implants were
      revised for aseptic loosening. Survivorship analysis of the McKee-Farrar
      prostheses had a 20-year probability of implant survivorship of 84%, and a 28
      year implant survivorship of 74%. Excellent long-term results of the McKee-Farrar
      prosthesis were seen. Given the inherent problems associated with implant wear
      debris, especially polyethylene wear particles, second generation metal-on-metal
      bearing implants may offer a viable alternative to current designs. Their
      excellent long-term survival may infer particular suitability for use in younger
      patients.

PMID- 12218480
TI  - Coding of diagnoses, comorbidities, and complications of total hip arthroplasty.
AB  - International Classification of Diseases coding of patient charts is used by
      hospitals to allow for billing of patients. Coding information also is used for
      assessing physician effectiveness. The purpose of the current study was to
      examine hospital coding for patients having total hip arthroplasty. One hundred
      consecutive primary total hip replacements were done at one medical center by two
      orthopaedic surgeons. Patient charts were coded by hospital coders according to
      the Health Care Finance Administration guidelines. Subsequently, an orthopaedist
      based team did a secondary review of these charts and the two sets of codes were
      compared. The diagnostic codes were similar between the two groups for 87% (174
      of 200 codes) of the cases. Comorbidities generally were undercoded by the
      hospital coders who reported 2.9 comorbidities per patient, whereas the secondary
      review reported 3.7 comorbidities per patient. The hospital coders found a
      complication rate of 1.2 per patient, whereas the secondary review revealed a
      rate of 0.4 per patient. Based on the results of the current study, the authors
      conclude that it is important to ensure three issues regarding the standard of
      coding and quality control: (1) the qualifications of the coders; (2) an
      interaction between coders and healthcare professionals to check that coding is
      accurate and reproducible; and (3) communication among various health
      professionals (including the primary surgeon) and coders to determine what
      actually are appropriate diagnoses, comorbidities, and complications.

PMID- 12218481
TI  - Increased perfusion of the femoral head in transient bone marrow edema syndrome.
AB  - The pathophysiology of transient bone marrow edema syndrome is not known.
      Ischemia has been suggested as the pathophysiologic factor, because the
      histologic findings are similar to those of early stage osteonecrosis.
      Angiographic studies of osteonecrotic femoral heads have shown arterial
      interruption and impaired perfusion. The current report describes the
      angiographic and scintigraphic findings of transient bone marrow edema syndrome
      of the hip in a 45-year-old man. The nutrient arteries were dilated, and the
      femoral head perfusion was increased compared with the unaffected contralateral
      side. These findings suggest that a vasomotor response plays a role in the
      pathogenesis of transient bone marrow edema syndrome. The disease might be a
      reversible process after temporary ischemia of the femoral head.

PMID- 12218482
TI  - Deformity correction followed by lengthening with the Ilizarov method.
AB  - Deformity combined with shortening of 18 lower limb segments of 17 patients was
      treated with the Ilizarov method. Limb lengthening was done at the same treatment
      (monofocal treatment) or a separate osteotomy (bifocal treatment) was done after
      acute or gradual correction of the deformity using the Ilizarov hinge system. The
      external fixation time, amount of deformity correction, length gained, and
      incidence of complications were examined. Results were compared between monofocal
      versus bifocal treatment groups and between femoral versus tibial procedures. The
      average deformity corrected was 22.3 degrees, and the average lengthening was
      44.4 mm. The external fixation index was 49.3 days/cm on average, ranging from
      24.4 to 90 days/cm, and the mean duration of external fixation was 198 days,
      ranging from 77 to 352 days. Major complications requiring surgical treatment,
      such as premature consolidation and fracture, were seen in four patients. There
      were no statistically significant differences between the results for monofocal
      and bifocal treatment or treatment indices for femoral and tibial operations. The
      Ilizarov method was very effective for treatment of limb deformity combined with
      shortening. Monofocal treatment might be better if the total amounts of
      lengthening required are short to reduce surgical invasion. Longer treatment
      indices for tibial operations could not be verified from the current study.

PMID- 12218483
TI  - Correction of combined angular and rotational deformities by the Ilizarov method.
AB  - Deformities of the lower extremities are often a combination of angular and
      rotational components. The rotational component of combined deformities may be
      difficult to measure using plain radiography. Based on the current study, the
      computed tomography rotational malalignment test was developed. Evaluation of
      lower extremity alignment was done on 56 patients. Rotational malalignment was
      diagnosed in 14 limbs of nine patients. In all patients, correction of angular
      and rotational deformities was done simultaneously using an Ilizarov external
      fixator. The frame included a standard angular distraction system and a
      derotation block interconnected via an additional empty ring. In all cases,
      successful correction of angular and rotational deformities was achieved. The
      pain was eliminated in all seven patients having preexisting chronic joint pain.
      There were no cases of deep infection or nonunion. This simple and reliable
      method allowed precise analysis of the deformity in the transverse plane.
      Preoperative frame construction incorporating the derotational module decreased
      the time of the operation and allowed one-stage correction of rotational and
      angular deformities without additional manipulations.

PMID- 12218484
TI  - Bone anatomy and rotational alignment in total knee arthroplasty.
AB  - The purpose of the current study was to investigate the bone anatomy in
      determining the rotational alignment in total knee arthroplasty using computed
      tomography. Axial images of 109 knees in 83 patients with varus osteoarthritis
      who had total knee arthroplasty were analyzed. On the images of the distal femur
      and the proximal tibia, a baseline for the anteroposterior axis of each component
      was drawn based on the epicondylar axis for the femur and the medial (1/3) of the
      tibial tuberosity for the tibia. The angle between these two lines was analyzed
      as the rotational mismatch between the components when they were aligned to the
      anatomic landmarks of each bone. Fifty-four knees (49.5%) had an angle of 5
      degrees or greater and 13 knees (11.9%) had an angle of 10 degrees or greater.
      There was a tendency to align the tibial component in external rotation relative
      to the femoral component. The results indicated that the landmarks of each bone
      were the intrinsic cause of the rotational mismatch in knees with varus
      osteoarthritis. Surgeons doing total knee arthroplasties should be aware of this
      and check the rotational mismatch between the components. When it is present, the
      tibial component should be realigned to match the femoral component rotation to
      minimize problems caused by the mismatch.

PMID- 12218485
TI  - Haemophilus influenza infection complicating a total knee arthroplasty.
AB  - Haemophilus influenza is rarely a cause of septic arthritis in adults. It has not
      been reported as a cause of infection in total knee arthroplasties. Haemophilus
      influenza septic arthritis is a late stage, hematogenous infection. A 43-year-old
      woman with a history of rheumatoid arthritis was found to have Haemophilus
      influenza infection 3 years after the index total knee arthroplasty. The patient
      was treated with debridement and systemic antibiotics. At the 5-year followup,
      the patient was comfortable and free of clinical signs of infection. This
      approach was successful at eradicating infection and salvaging the total knee
      arthroplasty.

PMID- 12218486
TI  - The radiologic prevalence of patellofemoral osteoarthritis.
AB  - The radiographs of 206 knees from 174 consecutive patients were reported blinded
      regarding joint space narrowing. Minimum joint space was measured using a
      millimeter ruler on weightbearing posteroanterior and skyline patellofemoral
      radiographs. Lateral radiographs were reported solely in terms of presence or
      absence of patellofemoral arthritis. The results showed objective joint space
      narrowing to less than 3 mm in the patellofemoral compartment of 32.7% of men and
      36.1% of women older than 60 years. This high prevalence of patellofemoral
      disease in men has not been documented before. Arthritic changes occurred in the
      patellofemoral compartment in isolation in 13.6% of women and 15.4% of men older
      than 60 years. The lateral radiograph had poor results for detection of
      patellofemoral osteoarthritis with a sensitivity of 66% and specificity of 83%.
      The positive predictive value of an abnormal lateral radiograph was 52%. If
      requests for skyline radiographs had been confined to patients with abnormal
      patellofemoral joints as assessed on lateral films then 28 normal joints would
      have been imaged and 14 abnormal joints would have been missed. Osteoarthritis is
      more common in the patellofemoral joints of men and women than previously
      documented and only can be properly assessed using a skyline radiograph.

PMID- 12218487
TI  - Ultrastructural features of giant cell tumors in Paget's disease.
AB  - Giant cell tumor is a rare complication of Paget's disease. This association is
      especially notable in patients originating from Avellino, Italy. Many types of
      evidence point to a viral etiology for Paget's disease and giant cell tumors
      arising in it. Three patients who had giant cell tumors and Paget's disease were
      studied. Two of the patients have a connection to Avellino (one was born in
      Avellino, and one descended from natives of Avellino). Distinctive light
      microscopic and ultrastructural features common in these three patients were
      identified. In all three patients, the giant cell tumors had peculiar irregular
      aggregates of microfilaments of uncertain genesis. The possibility that these
      reflect viral infection is discussed.

PMID- 12218488
TI  - Reconstruction of the pelvis after tumor resection in children and adolescents.
AB  - Thirty patients younger than 19 years with malignant bone tumors of the pelvis
      were treated by limb salvage surgery between 1970 and 1998. Functional and
      oncologic results were reviewed retrospectively. In 10 patients the defect was
      reconstructed by an endoprosthesis and in 20 patients reconstruction by
      autologous grafts (n = 7), allograft and prosthesis combinations (n = 2), bone
      cement reconstruction (n = 1), iliosacral arthrodesis (n = 1), modified
      Girdlestone procedure (n = 3), or resection without reconstruction (n = 6) was
      done. Three and one-half reoperations per patient were necessary postoperatively
      after allograft reconstruction, 2.5 reoperations per patient were necessary after
      endoprosthetic reconstruction, and 0.8 reoperations per patient were necessary
      after other or no reconstruction. After a mean followup of 52 months (range, 2
      241 months), 17 patients were alive, 15 of whom were continuously disease-free,
      and 13 patients had died of their disease. Functional ratings were 81% after
      autograft, 73% after allograft, and 60% after endoprosthetic reconstruction.
      Defect reconstruction varied according to the type of resection. Type I
      resections were best reconstructed by biologic methods. Endoprosthetic
      reconstruction after periacetabular resection with the advantage of preservation
      of a functional hip and body integrity was associated with a high rate of
      complications and reoperations. Its role compared with allograft reconstruction,
      modified Girdlestone procedure, or no reconstruction requires additional
      investigation.

PMID- 12218489
TI  - Biomechanical monitoring of healing bone based on acoustic emission technology.
AB  - Acoustic emission testing is a well-established method for assessment of the
      mechanical integrity of general construction projects. The purpose of the current
      study was to investigate the usefulness of acoustic emission technology in
      monitoring the yield strength of healing callus during external fixation. Thirty
      five patients with 39 long bones treated with external fixation were evaluated
      for fracture healing by monitoring load for the initiation of acoustic emission
      signal (yield strength) under axial loading. The major criteria for functional
      bone union based on acoustic emission testing were (1) no acoustic emission
      signal on full weightbearing, and (2) a higher estimated strength than body
      weight. The yield strength monitored by acoustic emission testing increased with
      the time of healing. The external fixator could be removed safely and
      successfully in 97% of the patients. Thus, the acoustic emission method has good
      potential as a reliable method for monitoring the mechanical status of healing
      bone.

PMID- 12218490
TI  - Intramedullary fixation for pediatric unstable forearm fractures.
AB  - Forty-nine children with diaphyseal both-bone forearm fractures were treated with
      either both-bone intramedullary wire fixation (24), single ulnar intramedullary
      wire fixation (22), or single radial intramedullary wire fixation (3). Six
      fractures were open and 43 were closed. A limited open approach to one or both
      bones was necessary for insertion of the intramedullary wire in 10 of 43 closed
      fractures. All both-bone and single radial intramedullary wire fixations healed
      with less than 5 degrees angulation. Progressive reangulation of the nonfixed
      radial fracture after an initial satisfactory reduction was seen in seven of the
      22 fractures treated with single ulnar intramedullary wire fixation. In four
      patients, the reangulation was controlled by a change of cast and molding of the
      fracture and was between 8 degrees and 12 degrees at union. In two other patients
      a second operative procedure was required to reduce and internally fix the
      radius. One fracture healed with a radial angulation of 25 degrees. Three
      fractures in older patients showed late reangulation after early removal of
      intramedullary wires at 5 weeks. The results of the current study suggest that
      the radius and ulna should be stabilized with intramedullary wires and that the
      wires should be buried to reduce the need for early removal.

PMID- 12218491
TI  - Flexor tendon repair using shape memory alloy suture: a biomechanical evaluation.
AB  - The purpose of the current study was to test in vitro a new shape memory alloy
      suture for flexor tendon repair. Forty fresh-frozen human anatomic flexor
      superficialis and profundus tendons were divided and repaired via the cruciate
      four-strand technique using one of two suture materials (the shape memory alloy
      suture and the 4-0 Ethibond suture). The forces required to cause a 1, 2, and 3
      mm gap, ultimate load to failure, and repair stiffness were compared. Twenty
      specimens of each suture material also were tensile tested for load to failure,
      tensile strength, and elongation at failure. The shape memory alloy suture had a
      significantly higher mean resistance force to 1, 2, and 3 mm gap formation than
      the 4-0 Ethibond suture (47 N versus 31 N, 51 N versus 36 N, and 57 N versus 41
      N, respectively). The shape memory alloy suture repair was 40% stronger than the
      4-0 Ethibond suture (61.9 +/- 8.8 N versus 44.3 +/- 10.6 N). Repair with the
      shape memory alloy suture was significantly stiffer than repair with the 4-0
      Ethibond suture (8.1 +/- 1.0 N/mm versus 6.1 +/- 0.9 N/mm). The load to failure
      and tensile strength of the shape memory alloy suture were significantly higher
      than that of the 4-0 Ethibond suture. The values of elongation for the two
      materials were not significantly different. The results of the current study
      suggest that the shape memory alloy suture may be superior to the 4-0 Ethibond
      suture in resisting gap formation in the range of forces generated in the early
      rehabilitation protocol and may be the future material of choice for tendon
      repairs.

PMID- 12218492
TI  - Gender differences in patellofemoral joint biomechanics.
AB  - Patellofemoral pain is associated with patellar malalignment and quadriceps
      weakness which are seen more commonly in women. The objective of the current
      study was to determine the effects of gender, vastus medialis strength, and
      tibial rotation on patellofemoral joint biomechanics. Twelve fresh-frozen knees
      from cadavers were tested using a custom knee jig. Anatomic multiplane loading of
      the extensor mechanism was used with varying vastus medialis loads.
      Patellofemoral contact area and pressure were measured using pressure sensitive
      film at knee flexion angles of 0 degrees, 30 degrees, 60 degrees, and 90 degrees
      with the tibia in neutral and 15 degrees internal and external tibial rotation.
      Patellofemoral joint contact areas in specimens from men were larger at knee
      flexion angles greater than 30 degrees. A significant increase in mean
      patellofemoral contact pressures was seen for specimens from women when compared
      with specimens from men at 0 degrees and 30 degrees knee flexion. The knees from
      women also showed a greater change in contact pressures to varying vastus
      medialis load at knee flexion angles of 0 degrees, 30 degrees, and 60 degrees.
      The results of the current study indicate that there are gender differences in
      patellofemoral contact areas and pressures. These differences may help explain
      the increased incidence of patellofemoral disorders in women.

PMID- 12218493
TI  - Effect of methylprednisolone on reperfusion after femoral head ischemia.
AB  - An episode of ischemia and reperfusion of the femoral head is thought to be the
      common pathway in the pathogenesis of femoral head necrosis. The influence of
      short-term high-dose steroid treatment on femoral head reperfusion after ischemia
      was investigated in a porcine model. Twenty-two pigs were randomized to receive
      methylprednisolone 20 mg/day/kg bodyweight intramuscularly for 3 days followed by
      methylprednisolone 10 mg/day/kg bodyweight for 11 days (n = 11), whereas the
      control group (n = 11) received no treatment. Femoral head ischemia was achieved
      by 6 hours of unilateral intraarticular hip pressure increase to 250 mm Hg.
      Femoral head blood flow was estimated using radiolabeled microspheres (15 microm
      in diameter) before ischemia, during hip tamponade, and 4 hours after tamponade
      release. Femoral head blood flow was lower in the corticosteroid treated pigs.
      Subtotal femoral head ischemia was documented in both groups during joint
      tamponade. Apart from two femoral head epiphyses in either group, reperfusion
      after tamponade release on the average occurred to a blood flow level similar to
      that before ischemia. Short-term high-dose methylprednisolone treatment depressed
      bone perfusion in general, but had no effect on reperfusion after femoral head
      ischemia in the porcine model.

PMID- 12218494
TI  - The effect of the amount of limb lengthening on skeletal muscle.
AB  - The adaptation of tibialis anterior muscles after 20% and 30% gradual limb
      lengthening was evaluated. Eight skeletally mature neutered male goats had 20% (n
      = 4) or 30% (n = 4) tibial distraction at a rate of 0.25 mm three times per day.
      Muscles from lengthened and contralateral control limbs were harvested on
      completion of distraction. Fiber length and sarcomere length were measured
      followed by calculation of sarcomere number and muscle fiber-to-bone lengthening
      ratio. Fiber length and sarcomere number after 20% and 30% limb lengthening were
      significantly greater in the distracted muscles, whereas no difference in
      sarcomere length was detected. The difference in muscle fiber length and
      sarcomere number between distracted and control limbs was greater in the 30% than
      in the 20% group. The disproportion between the amounts of muscle fiber and bone
      length increase was similar after 20% and 30% lengthening. The results show that
      muscular adaptation continues during 20% to 30% limb lengthening by increasing
      fiber length. It seems that this increase occurs through serial sarcomere
      addition rather than sarcomere length alteration. The higher rate of
      musclerelated clinical complications after limb lengthening beyond 20% does not
      seem to be related to a failure of muscle fiber contractile elements to adapt to
      increasing limb length.

PMID- 12218495
TI  - Arm pain in an 8-year-old boy.

PMID- 12218496
TI  - Strengthening the supraspinatus: a clinical and biomechanical review.
AB  - Rotator cuff weakness has been implicated as a cause of subacromial impingement.
      Numerous exercises have been advocated to strengthen the rotator cuff,
      particularly the supraspinatus. The clinical rationale and two exercises
      advocated for strengthening the supraspinatus, the empty can and the full can,
      were evaluated. By understanding how these exercises vary from a biomechanical
      perspective, it is hoped that clinicians can minimize the forces experienced by
      the supraspinatus during the rehabilitation process.

PMID- 12218497
TI  - Prevalence of common chronic pain in Hong Kong adults.
AB  - OBJECTIVE: Chronic pain is prevalent in many Western countries. Its prevalence in
      a non-Caucasian population is not known. The authors performed this study to
      measure the prevalence of chronic pain in the Hong Kong Chinese adult population,
      as well as the pattern of pain and the demographic characteristics, the impact on
      social and work function, and the help-seeking behavior of those with pain.
      DESIGN: Cross-sectional survey using telephone interview with a structured
      questionnaire. Chronic pain was defined as pain persisting for more than 3
      months. SUBJECTS: A random sample of over 1,000 persons out of the entire Chinese
      adult population of Hong Kong. RESULTS: One thousand fifty-one adults were
      interviewed. One hundred thirteen (10.8% [95% C.I.: 8.9%-12.7%]) had chronic
      pain. The median number of pains was two. Of those with chronic pain, 38.3%
      reported their work was affected, and 19.8% had taken a median of 5 days' sick
      leave in the past year; 70.8% said the pain had interfered with their daily life,
      88.5% had tried self-treatment, and 74.3% had sought medical advice. Only 35.7%
      considered the treatment definitely helpful. Two risk factors were identified:
      the female gender (O.R. 1.5, 95% C.I. 1.0-2.3) and age greater than 60 (O.R. 2.2,
      95% C.I. 1.3-3.6). CONCLUSIONS: The study showed that the prevalence of chronic
      pain in Hong Kong adults was approximately 10.8%. Work and daily life are
      significantly affected and there is considerable demand on the health care
      system. Despite the ethnic difference, the prevalence, pattern, and demographic
      characteristics of chronic pain in Hong Kong are very similar to those seen in
      Western countries.

PMID- 12218498
TI  - Dextromethorphan for phantom pain attenuation in cancer amputees: a double-blind
      crossover trial involving three patients.
AB  - BACKGROUND: Phantom limb pain is an intriguing pain syndrome that may result from
      damage to peripheral nerve tissue but could also involve central amplifying
      congeners. N-methyl-D-aspartate (NMDA)-receptor antagonists were recently shown
      to alleviate neuropathic pain in both animal and human models. Dextromethorphan
      is a noncompetitive NMDA-receptor antagonist. STUDY DESIGN: Oral dextromethorphan
      (120-180 mg daily) was administered to three selected cancer patients during a 3
      week study and an additional 1 month of treatment with the dosage subjectively
      judged to be best. RESULTS: Oral dextromethorphan effectively reduced
      postamputation phantom limb pain, bestowing improvement in feeling and minimizing
      sedation in comparison with the pretreatment or placebo conditions, with no side
      effects. Pain recurred in one patient 1 month after treatment was stopped.
      CONCLUSIONS: Further clinical trials are warranted to determine the optimal
      dosage and identify which patients with phantom pain would benefit the most from
      this therapeutic approach.

PMID- 12218499
TI  - Educational achievement and chronic pain disability: mediating role of pain
      related cognitions.
AB  - OBJECTIVE: This study examined the relation between level of educational
      achievement (LOE) and the clinical morbidity associated with chronic pain.
      SETTING: a multidisciplinary pain rehabilitation program located within a
      university hospital. PATIENTS: Two hundred ninety-nine consecutive patients with
      chronic spinal pain, average age 39.6 years (SD = 10.7) and with an average
      duration of pain of 41.9 months (SD = 51.6). OUTCOME MEASURES: Age, duration of
      pain, sex, and compensation and litigation status were controlled for in the
      statistical analysis because each was found to be significantly associated with
      LOE. Pain intensity was assessed by the McGill Pain Questionnaire. Affective
      distress was assessed by the Global Severity Index from the Brief Symptom
      Inventory. Severity of depressive symptoms was derived from scores from the
      Center for Epidemiological Studies-Depression Scale. Pain beliefs and pain coping
      strategies were assessed by the Survey of Pain Attitudes and the Coping
      Strategies Questionnaire, respectively. Finally, self-report of pain-related
      disability was assessed by the Pain Disability Index. RESULTS AND CONCLUSIONS:
      After controlling for relevant covariates, LOE was unrelated to pain intensity,
      severity of depressive symptoms, or affective distress, but was inversely related
      to self-reported disability. Persons with lower LOEs possessed a greater belief
      that pain is a "signal of harm," unrelated to emotional experience, disabling and
      uncontrollable. They also endorsed more passive and maladaptive coping
      strategies, including a tendency to catastrophize about their pain. Path analysis
      indicated that, after controlling for the influence of both the belief that pain
      is a "signal of harm" and catastrophizing on the association between LOE and
      disability, this relation loses statistical significance. These results suggest
      that pain-related cognitions mediate the relation between LOE and pain disability
      and that persons with lower LOEs are more likely to develop maladaptive pain
      beliefs and coping strategies.

PMID- 12218500
TI  - The lidocaine patch 5% effectively treats all neuropathic pain qualities: results
      of a randomized, double-blind, vehicle-controlled, 3-week efficacy study with use
      of the neuropathic pain scale.
AB  - BACKGROUND: Several controlled clinical trials have demonstrated the efficacy and
      safety of the lidocaine patch 5% (LP) for the treatment of postherpetic neuralgia
      (PHN). OBJECTIVE: To assess the effects of the LP on distinct neuropathic pain
      qualities common to all neuropathic pain conditions, the authors analyzed data
      from one of the vehicle-controlled trials in which the Neuropathic Pain Scale
      (NPS), the only assessment tool specifically designed to measure the distinct
      components of neuropathic pain, was administered. METHODS AND RESULTS: To improve
      the sensitivity of the NPS to treatment effects, only patients who, at the time
      of enrollment in the study, reported moderate-to-severe pain on the NPS (as
      defined by a score > or =4/10 reported for at least 6 of the 10 individual NPS
      items) were included in the analysis. Thus, 96 patients were included in this
      analysis. After a 3-week, vehicle-controlled study, LP improved all assessed pain
      qualities to a greater extent than the placebo patch, as measured by the NPS 10,
      a sum score including all 10 NPS item scores ( = 0.043), and an NPS 8 score,
      which included scores for all 8 pain descriptors, excluding "unpleasantness" and
      "global intensity" ( = 0.042). Separate analysis of all 8 items believed not to
      reflect allodynia (NPS NA; excluding "skin sensitivity" and "surface pain") also
      demonstrated superiority ( = 0.022), as did analysis of the subitems that are
      believed not to be primarily related to peripheral pathophysiological events (the
      "NPS 4": "sharp," "hot," "dull," and "deep" pains; = 0.013). CONCLUSIONS: This
      study demonstrates that LP reduces the intensity of all common neuropathic pain
      qualities and thus may be of potential benefit for nonallodynic neuropathic pain
      states. Furthermore, these findings suggest that peripheral mechanisms may play a
      role in the pathophysiological development of pain qualities that heretofore have
      been assumed not to involve peripheral mechanisms, such as "dull," "deep,"
      "sharp," and "burning" pains.

PMID- 12218501
TI  - Contribution of individual spa therapies in the treatment of chronic pain.
AB  - OBJECTIVES: The aim of the present study was to evaluate the contribution of
      individual spa therapies administered during a period of 3 weeks on measures of
      well being and pain in a sample of patients with chronic back pain. DESIGN: One
      hundred fifty-three patients with chronic back pain undergoing inpatient spa
      therapy in Bad Tatzmannsdorf, Austria, participated in the study. According to
      the prescription of their spa physician, patients underwent two or more of the
      following treatments: mud packs, carbon dioxide baths, massages, exercise
      therapies, spinal traction, and electrotherapy. The outcome measures were general
      pain, back pain, negative mood, and health satisfaction. Regression analyses were
      conducted to predict the 4 outcome measures at the end of spa therapy and at 6
      weeks' follow-up for all therapies applied. The pretreatment outcome measure,
      age, and sex were controlled for by entering them into the analysis. RESULTS:
      Patients showed significant improvements in all 4 outcome measures. The
      prediction of improvement was generally small: only 1% to 11% of the change of
      the outcome measures could be explained by the type and number of therapies
      received. On a short-term basis, mud packs and exercise were found to be
      associated with a greater improvement in mood, whereas a greater frequency of
      massage therapy and carbon dioxide baths was associated with a smaller
      improvement in health satisfaction. On a long-term basis, exercise therapy and
      spinal traction were associated with a greater reduction in back pain.
      CONCLUSIONS: The results indicate that, in addition to the individual therapies,
      other factors relating to spa therapy as a whole must contribute to overall
      treatment outcome. In addition, the results support the efficacy of exercise
      therapy for chronic back pain.

PMID- 12218502
TI  - Observational visual analog scale in pediatric pain assessment: useful tool or
      good riddance?
AB  - DESIGN: The authors reviewed the available pediatric pain literature and selected
      those studies that reported quantitative information on the reliability and
      validity of, and the optimal cutoff points for, the visual analog scale (VAS)
      when used as an observational pediatric pain tool. RESULTS: Available
      psychometric findings concerning the observational VAS (VAS obs ) are limited.
      The estimated interrater reliability of the VAS (obs) from 9 studies ranged from
      0.36 to 0.91. The correlation between self-report and the VAS (obs) was variable
      and ranged 0.23 to 0.83 in 6 studies. The concurrent validity of the VAS (obs)
      and other pain instruments ranged from 0.42 to 0.86. CONCLUSIONS: Further
      psychometric testing needs to be conducted on intraobserver reliability,
      responsiveness, and optimal cutoff points. Future research may guide the choice
      between VAS (obs) and the numerous behavioral pain instruments.

PMID- 12218503
TI  - Does postoperative pain induce emesis?
AB  - OBJECTIVE: The aim of this prospective, controlled study was to evaluate the risk
      factors for postoperative emesis in patients undergoing gynecologic surgery and
      receiving patient-controlled analgesia for three days. METHODS: Six hundred
      twenty-five gynecologic patients with an American Society of Anesthesiologists
      physical status of I to III undergoing lower-abdominal surgeries were enrolled. A
      standard, general anesthetic technique was used. Postoperative pain was treated
      by a patient-controlled analgesia device with bolus intravenous doses of 1 mg
      morphine. For 3 days after surgery patients were assessed for occurrence of
      emesis, sedation, and pain intensity when at rest and during movement. RESULTS:
      The incidence of emesis was 26% on postoperative day 1, 13% on day 2, and 4% on
      day 3. On all 3 days, patients' pain scores when at rest and when coughing were
      higher for those with emesis than for those without. During the first 2
      postoperative days the patients with and those without emesis consumed similar
      amounts of morphine daily, but on the third day the patients with emesis consumed
      significantly more morphine than did those without emesis ( <0.05). Further
      logistic regression analysis showed that incident pain was the main risk factor
      for postoperative emesis on all 3 days. CONCLUSIONS: The results suggested that
      postoperative pain was an associative risk factor to increase the incidence of
      emesis in these female patients.

PMID- 12218504
TI  - Systematic review of randomized controlled trials of nonpharmacological
      interventions for fibromyalgia.
AB  - OBJECTIVE: Little is known of the effectiveness of nonpharmacological
      interventions for fibromyalgia syndrome (FMS). The authors therefore carried out
      a systematic review from 1980 to May 2000 of randomized controlled trials (RCTs)
      of nonpharmacological interventions for FMS. METHOD: A search of computerized
      databases was supplemented by hand searching of bibliographies of key
      publications. The methodological quality of studies included in the review was
      evaluated independently by two researchers according to a set of formal criteria.
      Discrepancies in scoring were resolved through discussion. RESULTS: The review
      yielded 25 RCTs, and the main categories of interventions tested in the studies
      were exercise therapy, educational intervention, relaxation therapy, cognitive
      behavioral therapy, acupuncture, and forms of hydrotherapy. Methodological
      quality of studies was fairly low (mean score = 49.5/100). Most studies had small
      samples (median for individual treatment groups after randomization = 20), and
      the mean power of the studies to detect a medium effect ( > or = 0.5) was 0.36.
      Sixteen studies had blinded outcome assessment, but patients were blinded in only
      6 studies. The median longest follow-up was 16 weeks. Statistically significant
      between-group differences on at least one outcome variable were reported in 17 of
      the 24 studies. CONCLUSIONS: The varying combinations of interventions studied in
      the RCTs and the wide range of outcome measures used make it hard to form
      conclusions across studies. Strong evidence did not emerge in respect to any
      single intervention, though preliminary support of moderate strength existed for
      aerobic exercise. There is a need for larger, more methodologically rigorous RCTs
      in this area.

PMID- 12218505
TI  - The differential effect of haloperidol and repetitive induction on four
      immobility responses in mouse and guinea pig.
AB  - The modification by haloperidol and repetitive induction on four immobility
      responses -- tonic immobility, cataleptic immobility, immobility by clamping the
      neck and dorsal immobility -- were compared in mice and guinea pigs. Without
      drug, three out of four responses (cataleptic, neck clamp and dorsal immobility)
      were induced in mice; guinea pigs displayed all four responses. Haloperidol (5
      mg/kg i.p.) potentiated the three responses shown by mice, but did not potentiate
      the four responses in guinea pigs. In both undrugged and haloperidol-treated
      mice, only the cataleptic immobility response was potentiated by repetition. In
      guinea pigs, none of the four immobility responses was affected due to
      repetition, haloperidol or a combination of both. These data are discussed,
      considering that, although these immobility responses could be mediated by the
      same neurotransmitters (e.g. dopamine), they are possibly expressed in a
      differential manner as a function of the kind of stimulus used to trigger the
      response, characteristics of the species and, in some immobility responses such
      as cataleptic immobility, as a function of their interaction with habituation or
      another learning-like process.

PMID- 12218506
TI  - Tonic immobility in guinea pigs: a behavioural response for detecting an
      anxiolytic-like effect?
AB  - Tonic immobility (TI) is considered to be an innate fear response characterized
      by a temporary state of profound and reversible motor inhibition. TI occurs in a
      wide range of species in a predator-prey confrontation and is hypothesized to be
      a terminal defence response occurring when there is physical contact between prey
      and predator. The objective of the present study was to investigate the validity
      of the TI model in guinea pigs for detection of anxiolytic and/or antidepressant
      drug activity. Compounds that reduced TI include the serotonin (5-HT) releaser
      fenfluramine, the 5-HT(1A) receptor agonists 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT) and buspirone, the 5-HT(2C/2B) receptor
      antagonist SB206553, the 5-HT(2A) receptor antagonist MDL 100.151 -- but only at
      doses thought also to inhibit 5-HT(2C) receptors--the noradrenaline (NA) reuptake
      inhibitor desipramine, the benzodiazepine inverse agonist FG-7142, the alpha(2)
      adrenergic receptor antagonist yohimbine, the neurokinin (NK)(1) receptor
      antagonist L-733.060, and the NK(2) receptor antagonist SR-48968. Compounds that
      increased TI include the benzodiazepine agonists diazepam and alprazolam, and the
      alpha(2)-adrenergic receptor agonist clonidine. The selective 5-HT reuptake
      inhibitors citalopram, paroxetine and fluoxetine, the 5-HT(1A) receptor
      antagonist WAY100.635, the 5-HT(2C) receptor agonist MK-212, the 5-HT/NA reuptake
      inhibitor imipramine, the NA reuptake inhibitor talopram, the benzodiazepine
      antagonist flumazenil, the alpha(2)-adrenergic receptor antagonist idazoxan and
      the psychostimulant amphetamine did not have any effect. These findings indicate
      that the serotonergic, noradrenergic and neurokinin systems are involved in
      mediating or modulating TI behaviour in guinea pigs. The potential of TI as a
      behaviour for detecting anxiolytic-like effect may be questioned due to the
      contradictory effect of the benzodiazepine ligands, which may be attributed to
      the sedative and/or ataxic effects of the compounds. Nevertheless, there is
      preclinical evidence suggesting that 5-HT(1A) receptor agonists, 5-HT(2C)
      receptor antagonists and NK(1) and NK(2) receptor antagonists possess anxiolytic
      potential. Only when results of clinical investigations of the anxiolytic
      potential of non-benzodiazepine ligands (for example the NK receptor antagonists)
      are available, will it be possible to determine fully the predictive validity of
      the TI model.

PMID- 12218507
TI  - An analysis of the utility of differential outcome procedures in drug
      discrimination research.
AB  - In differential outcomes procedures, the correlation of unique reinforcers with
      distinct discriminative stimuli can decrease the amount of time needed for
      response acquisition and improve terminal accuracy of responding. The drug
      discrimination assay is widely used to categorize psychoactive drugs as similar
      or dissimilar and to describe underlying neurochemical changes associated with
      drug administration. Because the drug discrimination assay relies heavily upon
      initial response acquisition and continuing terminal accuracy, a procedure
      successful at shortening acquisition time and improving terminal accuracy would
      be beneficial. The present studies examined differences in acquisition of drug
      stimulus control between rats exposed to differential outcome procedures and rats
      exposed to the outcomes, in a non-systematic way, in two experiments. The first
      experiment examined acquisition of control by (+/-)-3,4
      methylenedioxymethamphetamine (MDMA), D-amphetamine and saline; the second
      examined control by MDMA, (+)-lysergic acid diethylamide (LSD) and saline.
      Neither initial acquisition nor terminal accuracy was influenced by differential
      outcomes in either experiment. Although the differential outcome effect has been
      demonstrated in many situations, it does not appear to be useful in the drug
      discrimination assay. Possible reasons for the lack of an observed effect are
      discussed.

PMID- 12218508
TI  - Changes in behavioural contingencies produce a loss of tolerance to amphetamine
      hypophagia in rats despite continued feeding tests while drugged.
AB  - Rats administered amphetamine prior to access to milk in bottles develop
      tolerance to the hypophagic effect of the drug by learning to suppress
      stereotyped behaviours that interfere with feeding. When tolerant rats are later
      allowed to drink milk from a bottle in an unintoxicated state, tolerance is lost,
      even when drug exposure is held constant by administration of the drug after the
      test. In the present experiment, we show that tolerance can also be lost in the
      face of continued administration of amphetamine prior to milk tests, as a result
      of changes in the contingencies of reinforcement that govern the suppression of
      stereotypy. Rats were injected with 2 mg/kg amphetamine and given access to milk
      in bottles for 16 trials. Tolerance to the hypophagic effect was confirmed by
      dose-response tests in which milk was available in bottles. The rats were then
      injected with 2 mg/kg amphetamine prior to intraoral milk infusions for 21
      trials. This method of feeding did not require the suppression of stereotypy to
      obtain milk. Subsequent dose-response tests in which milk was again presented in
      bottles revealed that tolerance was lost, even though intoxicated feedings were
      never interrupted. These results demonstrate that the contingencies of
      reinforcement governing the suppression of stereotypy determine whether tolerance
      is retained or lost.

PMID- 12218509
TI  - MK-801 disrupts acquisition of contextual fear conditioning but enhances memory
      consolidation of cued fear conditioning.
AB  - The effects of pre-training or post-training subcutaneous injections of multiple
      doses of the non-competitive NMDA-receptor antagonist (+)-5-methyl-10,11-dihydro
      5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) on cued and contextual
      fear conditioning were examined in F344 rats. Pre-training injections of MK-801
      (0.3 and 1.0 mg/kg) disrupted contextual fear conditioning but not cued fear
      conditioning. Post-training injections of MK-801 did not disrupt cued or
      contextual fear conditioning. In fact, the 0.3 mg/kg dose of MK-801 enhanced cued
      fear conditioning. Finally, rats were tested for MK-801-induced alterations in
      sensitivity to pain using the formalin test for nociception. MK-801 did not
      reduce sensitivity to pain. These results suggest that NMDA receptors are
      involved in acquisition of contextual fear conditioning but not in memory
      consolidation of the learned response.

PMID- 12218510
TI  - The effects of selective dopamine agonists on a passive avoidance learning task
      in the day-old chick.
AB  - Recent examination of the mixed dopamine agonist apomorphine suggests that
      dopamine inhibits both passive avoidance and response suppression learning. The
      present study investigated the effects of selective dopamine agonists on memory
      consolidation using a passive avoidance task in the day-old chick. The dopamine
      D1 agonist SKF 38393, the D2 agonist quinpirole, and the D4 agonist PD 168077 all
      failed to disrupt memory consolidation when injected immediately after training.
      However, chicks injected with 6.0 mg/kg of the D3 agonist (+)-7-hydroxy-N,N-di-n
      propyl-2-aminotetralin (7-OH-DPAT) displayed memory impairment 180 min after
      aversive training. A study of the time course of this effect of 7-OH-DPAT showed
      that it first appeared 90 min after aversive training. Pretreatment with the
      dopamine D3 antagonist U 99194 eliminated the disturbance of passive avoidance
      learning induced by 7-OH-DPAT. These results indicate that dopamine is involved
      in the later stages of the memory formation process and that the D3 receptor is
      crucially involved in this disruption.

PMID- 12218511
TI  - Full substitution of the discriminative cue of a 5-HT(1A/1B/2C) agonist with the
      combined administration of a 5-HT(1B/2C) and a 5-HT(1A) agonist.
AB  - The present study examined whether animals attend to the individual components of
      the cue produced by a drug that stimulates different 5-hydroxytryptamine (5-HT)
      receptor populations, using a drug discrimination task based on the conditioned
      taste aversion (CTA) procedure. The training drug was indorenate (5
      methoxytryptamine beta-methylcarboxylate) (INDO) that has been described as a 5
      HT(1A/2C/1B) agonist able to exert discriminative control in both operant and CTA
      procedures. The principal objective was to examine generalization with the
      combined administration of agonists for the different receptor sites that may
      mimic the mechanism of action of the training drug. Male Wistar rats, deprived of
      water, were trained to discriminate INDO from saline; during the drug trials, the
      administration of INDO preceded saccharin-LiCl pairings, while, during the saline
      trials, the administration of saline preceded the saccharin-saline pairings. In
      generalization tests, INDO, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a
      5-HT(1A) agonist), 1-(3-trifluoromethylphenyl)piperazine (TFMPP, a 5-HT(1B)
      agonist), alpha-methyl-5-HT (a 5-HT(2C) agonist) or 2-methyl-5-HT (a 5-HT(3)
      agonist), were administered alone or in combination. The results showed that 8-OH
      DPAT, TFMPP and alpha-methyl-5-HT produced dose-dependent generalization, up to
      88% in the case of 8-OH-DPAT. The combined administration of the following pairs
      of drugs, 8-OH-DPAT+TFMPP or 8-OH-DPAT+ alpha-methyl-5-HT, at doses that produced
      only 15-55% generalization when administered alone, produced greater than 80%
      generalization to INDO. However, the single administration of 2-methyl-5-HT
      produced only saline-like responding and its combined administration with 8-OH
      DPAT did not modify the generalization produced by the single administration of 8
      OH-DPAT. These results suggest that animals attend to the individual components
      of the drug cue; in the case of INDO, which has three elements, each mediated by
      a different receptor subpopulation (5-HT(1A), 5-HT(1B) and 5-HT(2C) ), the
      separate stimulation of at least two receptor subpopulations was 'interpreted' by
      the subject as the presence of the training drug.

PMID- 12218512
TI  - Role of 5-HT(2) receptors in the tryptamine-induced 5-HT syndrome in rats.
AB  - We distinguished the functions of the different 5-hydroxytryptamine-2 (5-HT(2))
      receptor (5-HT(2)R) subtypes in the tryptamine-induced 5-HT syndrome in rats
      using (1) the 5-HT(2A)R antagonist R93274 (N-[(3-p-fluorophenyl-1-propyl)-4
      methyl-4-piperidinyl]-4-amino-5-iodo-2-methoxybenzamide), the 5-HT(2A/C)R
      antagonist R99647 (2-(dimethylaminomethyl)2,3,3a,8
      tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine), the 5-HT(2B/C)R antagonist SB
      242084 (6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]
      indoline), and several 5-HT(2)R antagonists (ketanserin, risperidone, pipamperone
      and mianserin); and (2) chronic 5-HT(2)R activation by 1-(2,5-dimethoxy-4
      methylphenyl)-2-aminopropane (DOM). In contrast to SB-242084, the selective 5
      HT(2A)R antagonist R93274 as well as the non-selective 5-HT(2A)R antagonists
      (R99647, ketanserin, risperidone, pipamperone and mianserin) significantly
      inhibited tryptamine-induced forepaw treading and tremors, and reversed
      peripherally mediated cyanosis into hyperaemia; only the 5-HT(2A/C)R antagonists
      R99647 and mianserin inhibited the tryptamine-induced hunched back. Intermittent
      DOM administration (intravenously every 48 h for 12 days) did not change the
      centrally mediated tryptamine-induced forepaw treading, tremors and hunched back
      at 1, 4 or 7 days after the last DOM pretreatment. The DOM-induced head twitch
      response, measured immediately after every DOM injection, was not affected. In
      contrast, peripherally mediated cyanosis was reversed into hyperaemia in 75, 11
      and 20% of all pretreated rats at 1, 4 and 7 days, respectively, after the last
      DOM administration. Taken together, these finding suggest that central 5-HT(2A)Rs
      mediate tryptamine-induced forepaw treading and tremors, that peripheral 5-HT Rs
      mediate tryptamine-induced cyanosis, and that 5-HT(2A)Rs mediate tryptamine
      induced hunched back. Peripheral 5-HT(2C)Rs are more sensitive to desensitization
      after intermittent treatment with an agonist than central 5-HT(2A)Rs.

PMID- 12218513
TI  - Interaction between midazolam-induced anterograde amnesia and memory enhancement
      by treatments given immediately after training on an inhibitory avoidance task in
      rats.
AB  - The aim of this study was to evaluate the effects of interactions between memory
      modulatory systems on inhibitory avoidance retention in rats. Adult female Wistar
      rats were trained and tested in a step-down inhibitory avoidance task (0.3 mA
      footshock). The training-test interval was 24 h. The animals received an
      intraperitoneal injection of saline or midazolam (1 mg/kg) 15 min before
      training, and saline, adrenaline (25 microg/kg), naloxone (0.4 mg/kg),
      dexamethasone (0.3 mg/kg) or glucose (320 mg/kg) immediately after training. In
      saline-pretreated rats, adrenaline, naloxone, dexamethasone and glucose enhanced
      memory retention. Pretreatment with midazolam prevented the facilitatory effects
      of those treatments. These findings suggest that the facilitation of learning by
      post-training memory-enhancing treatments is prevented by midazolam.

PMID- 12218515
TI  - Optimizing postoperative analgesia: the use of global outcome measures.

PMID- 12218516
TI  - Frontiers in translational research: the etiology of incisional and postoperative
      pain.

PMID- 12218517
TI  - Is gabapentin a "Broad-spectrum" analgesic?

PMID- 12218518
TI  - Epidural analgesia enhances functional exercise capacity and health-related
      quality of life after colonic surgery: results of a randomized trial.
AB  - BACKGROUND: Multimodal analgesia programs have been shown to decrease hospital
      stay, but it not clear which functions are restored after surgery. The objective
      of this study is to evaluate the impact of epidural anesthesia and analgesia on
      functional exercise capacity and health-related quality of life. METHODS: Sixty
      four patients undergoing elective colonic resection were randomized to either
      patient-controlled analgesia with morphine or thoracic epidural analgesia with
      bupivacaine and fentanyl (epidural group). All patients in both groups received
      similar perioperative care and were offered the same amount of postoperative oral
      nutrition and assistance with mobilization. Primary outcome was functional
      exercise capacity as measured by the 6-min walking test, and secondary outcome
      was health-related quality of life, as measured by the SF-36 health survey. These
      were assessed before surgery and at 3 and 6 weeks after hospital discharge. Other
      variables measured in hospital included pain and fatigue visual analogue scale,
      bowel function, time out of bed, nutritional intake, complication rate, readiness
      for discharge, and length of hospital stay. RESULTS: Although the 6-min walking
      test and the SF-36 physical health component decreased in both groups at 3 and 6
      weeks after surgery, the patient-controlled analgesia group experienced a
      significantly greater decrease at both times (P < 0.01). Patients in the epidural
      group had lower postoperative pain and fatigue scores, which allowed them to
      mobilize to a greater extent (P < 0.05) and eat more (P < 0.05). Length of
      hospital stay and incidence of complications were similar in both groups,
      although patients in the epidural group were ready to be discharged earlier.
      CONCLUSIONS: The superior quality of pain relief provided by epidural analgesia
      had a positive impact on out-of-bed mobilization, bowel function, and intake of
      food, with long-lasting effects on exercise capacity and health-related quality
      of life.

PMID- 12218519
TI  - Different mechanisms of development and maintenance of experimental incision
      induced hyperalgesia in human skin.
AB  - BACKGROUND: To determine the mechanisms of postoperative pain, the effects of
      local anesthesia on development and maintenance of surgical incision-induced
      hyperalgesia were evaluated in a crossover, double-blinded, placebo-controlled
      human study using 17 subjects. METHODS: An experimental 4-mm-long incision
      through skin, fascia, and muscle was made in the volar forearm of each subject.
      In experiment 1, 1% lidocaine or saline in a volume of 0.2 ml was subcutaneously
      injected into the incision site pretraumatically and posttraumatically. In
      experiment 2, a 5-cm-long strip of skin was subcutaneously injected with 0.2 ml
      of 1% lidocaine near the incision site pretraumatically and posttraumatically.
      Flare, spontaneous pain, and primary and secondary hyperalgesia to punctate
      mechanical stimuli were assessed after the incision had been made. RESULTS:
      Pretraumatic lidocaine injection prevented the occurrence of spontaneous pain and
      development of flare formation that was found surrounding the incision site
      immediately (1 min) after the incision had been made. The lidocaine suppressed
      primary hyperalgesia more effectively than did posttraumatic block, but only for
      the first 4 h after the incision. The preincision block prevented development of
      secondary hyperalgesia, whereas posttraumatic block did not significantly affect
      the fully developed secondary hyperalgesia. The area of flare formation and the
      area of secondary hyperalgesia did not extend over the strip of the skin that had
      been pretraumatically anesthetized, whereas the posttraumatic block did not
      significantly reduce the area of fully developed secondary hyperalgesia.
      CONCLUSIONS: Pretraumatic injection of lidocaine reduces primary hyperalgesia
      more effectively than does posttraumatic injection, but only for a short period
      after incision. The spread of secondary hyperalgesia is mediated peripheral nerve
      fibers, but when secondary hyperalgesia has fully developed, it becomes less
      dependent on or even independent of peripheral neural activity originating from
      the injured site.

PMID- 12218520
TI  - A randomized study of the effects of single-dose gabapentin versus placebo on
      postoperative pain and morphine consumption after mastectomy.
AB  - BACKGROUND: The anticonvulsant gabapentin has proven effective for neuropathic
      pain in three large placebo-controlled clinical trials. Experimental and clinical
      studies have demonstrated antihyperalgesic effects in models involving central
      neuronal sensitization. It has been suggested that central neuronal sensitization
      may play an important role in postoperative pain. The aim of the study was to
      investigate the effect of gabapentin on morphine consumption and postoperative
      pain in patients undergoing radical mastectomy. METHODS: In a randomized, double
      blind, placebo-controlled study, 70 patients received a single dose of oral
      gabapentin (1,200 mg) or placebo 1 h before surgery. Patients received patient
      controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10
      min for 4 h postoperatively. Pain was assessed on a visual analog scale at rest
      and during movement, and side effects were assessed on a four-point verbal scale
      2 and 4 h postoperatively. RESULTS: Thirty-one patients in the gabapentin group
      and 34 patients in the placebo group completed the study. Gabapentin reduced
      total morphine consumption from a median of 29 (interquartile range, 21-33) to 15
      (10-19) mg (P< 0.0001). Pain during movement was reduced from 41 (31-59) to 22
      (10-38) mm at 2 h postoperatively (P < 0.0001) and from 31 (12-40) to 9 (3-34) mm
      at 4 h postoperatively (P = 0.018). No significant differences between groups
      were observed with regard to pain at rest or side effects. CONCLUSION: A single
      dose of 1,200 mg oral gabapentin resulted in a substantial reduction in
      postoperative morphine consumption and movement-related pain after radical
      mastectomy, without significant side effects. These promising results should be
      validated in other acute pain models involving central neuronal sensitization.

PMID- 12218521
TI  - A single preoperative oral dose of valdecoxib, a new cyclooxygenase-2 specific
      inhibitor, relieves post-oral surgery or bunionectomy pain.
AB  - BACKGROUND: The trend toward day-case surgery, with discharge on oral medication,
      has highlighted the need for effective and safe analgesics that facilitate a
      rapid recovery and discharge time. This study evaluated the analgesic efficacy,
      dose dependency, duration of action, and safety of the cyclooxygenase-2 specific
      inhibitor, valdecoxib, administered before oral or orthopedic surgery. METHODS:
      Eligible healthy adult patients were scheduled to undergo either extraction of
      two impacted third molar teeth (n = 284) or bunionectomy surgery (n = 223) with
      local anesthesia in two randomized, double-blind, placebo-controlled studies
      conducted at three centers in the United States. Patients received a single,
      preoperatively administered oral dose of placebo or 10 (oral surgery only), 20,
      40, or 80 mg valdecoxib. Analgesic efficacy was assessed postoperatively, over a
      24-h treatment period, or until the patient required rescue medication. Efficacy
      measures included time to rescue medication, proportion of patients requiring
      such rescue, pain intensity, and the Patient's Global Evaluation of Study
      Medication. RESULTS: In both studies, all doses of valdecoxib produced analgesia
      with a duration (time to rescue analgesia) and magnitude (Pain Intensity,
      Patient's Global Evaluation) significantly greater than placebo. A dose-dependent
      effect was observed up to 40 mg valdecoxib, with an 80-mg dose providing no
      additional analgesic benefit. In both models, all doses of valdecoxib were well
      tolerated, with no clinically significant treatment-related gastrointestinal,
      renal, or platelet-derived adverse events, and no evidence of a dose-related
      increase in adverse events. CONCLUSIONS: Preoperative orally administered
      valdecoxib provides well-tolerated and effective analgesia for mild to moderate
      postoperative pain.

PMID- 12218522
TI  - A comparison of the 24-gauge Sprotte and Gertie Marx spinal needles for combined
      spinal-epidural analgesia during labor.
AB  - BACKGROUND: Prior experience with the combined spinal-epidural technique (CSE)
      for labor analgesia demonstrated a high (up to 14%) failure rate because of
      failure to obtain cerebrospinal fluid (CSF) or lack of response to appropriate
      doses of intrathecal sufentanil. The current study was designed to test whether a
      longer needle with a shorter side port (Gertie Marx needle; 127 mm long) would
      eliminate failures to obtain CSF compared with the needle we had used previously
      (Sprotte needle; 120 mm long). METHODS: Seventy-three parturients were randomly
      assigned to have a CSE performed with one of these two needles. After identifying
      the epidural space with an 18-gauge Touhy needle at the L2-L3 or L3-L4
      interspace, the spinal needle was introduced through the Touhy needle until
      penetration of the dura was felt or until the needle was maximally inserted. If
      no CSF was obtained, the alternate needle was tried. After obtaining CSF, 10
      microg sufentanil diluted in 1.8 ml saline was injected. Verbal pain scores (0
      10) were obtained every 5 min for 30 min. RESULTS: Failure to obtain CSF occurred
      six times in the Sprotte group compared with none in the Gertie Marx group (P <
      0.05). In all six failures in the Sprotte group, the Gertie Marx needle
      subsequently proved successful in obtaining CSF. There were no differences in
      pain scores between the groups. CONCLUSIONS: The extra length of the 127-mm
      Gertie Marx needle resulted in a higher success rate for obtaining CSF when used
      in the CSE technique. Side port design was not a factor influencing success in
      this clinical setting.

PMID- 12218523
TI  - Low-flow sevoflurane compared with low-flow isoflurane anesthesia in patients
      with stable renal insufficiency.
AB  - BACKGROUND: Sevoflurane is degraded to compound A (CpA) by carbon dioxide
      absorbents containing strong base. CpA is nephrotoxic in rats. Patient exposure
      to CpA is increased with low fresh gas flow rates, use of Baralyme, and high
      sevoflurane concentrations. CpA formation during low-flow and closed circuit
      sevoflurane anesthesia had no significant renal effects in surgical patients with
      normal renal function. Preexisting renal insufficiency is a risk factor for
      postoperative renal dysfunction. Although preexisting renal insufficiency is not
      affected by high-flow sevoflurane, the effect of low-flow sevoflurane in patients
      with renal insufficiency is unknown. METHODS: After obtaining institutional
      review board approval, 116 patients with a stable preoperative serum creatinine
      concentration 1.5 mg/dl or greater were assessable. Patients were randomized to
      receive either sevoflurane (n = 59, 0.8-2.5 vol%) or isoflurane (n = 57, 0.5-1.4
      vol%) at a fresh gas flow rate of 1 l/min or less. Use of opioids was restricted
      to a minimum, and Baralyme was used to increase CpA exposure. Inspiratory and
      expiratory CpA concentrations were measured during anesthesia. Renal function
      (serum creatinine and blood urea nitrogen, urine protein and glucose, creatinine
      clearance) was measured preoperatively and 24 and 72 h after induction. RESULTS:
      Demographic patient data did not differ between groups. Patients received 3.1 +/-
      2.4 minimum alveolar concentration-hours sevoflurane or 3.8 +/- 2.6 minimum
      alveolar concentration-hours isoflurane (mean +/- SD). Durations of low flow were
      201.3 +/- 98.0 and 213.6 +/- 83.4 min, respectively. Maximum inspiratory CpA with
      sevoflurane was 18.9 +/- 7.6 ppm (mean +/- SD), resulting in an average total CpA
      exposure of 44.0 +/- 30.6 ppm/h. There were no statistically significant changes
      from baseline to 24- and 72-h values for serum creatinine or blood urea nitrogen,
      creatinine clearance, urine protein, and glucose, nor were there significant
      differences between both anesthetics. CONCLUSION: There were no statistically
      significant differences in measured parameters of renal function after low-flow
      sevoflurane anesthesia compared with isoflurane. These results suggest that low
      flow sevoflurane anesthesia is as safe as low-flow isoflurane and does not alter
      kidney function in patients with preexisting renal disease.

PMID- 12218524
TI  - Clinical trial of the neuroprotectant clomethiazole in coronary artery bypass
      graft surgery: a randomized controlled trial.
AB  - BACKGROUND: The neuroprotective property of clomethiazole has been demonstrated
      in several animal models of global and focal brain ischemia. In this study the
      authors investigated the effect of clomethiazole on cerebral outcome in patients
      undergoing coronary artery bypass surgery. METHODS: Two hundred forty-five
      patients scheduled for coronary artery bypass surgery were recruited at two
      centers and prospectively randomized to clomethiazole edisilate (0.8%), 225 ml
      (1.8 mg) loading dose followed by a maintenance dose of 100 ml/h (0.8 mg/h)
      during surgery, or 0.9% NaCl (placebo) in a double-blind trial. Coronary artery
      grafting was completed during moderate hypothermic (28-32 degrees C)
      cardiopulmonary bypass. Plasma clomethiazole was measured at several intervals
      during and up to 24 h after the end of infusion. A battery of eight
      neuropsychological tests was administered preoperatively and repeated 4-7 weeks
      after surgery. Analysis of the change in neuropsychological test scores from
      baseline was used to determine the effect of treatment. RESULTS:
      Neuropsychological assessments were completed in 219 patients (110 clomethiazole;
      109 placebo). The mean plasma concentration of clomethiazole during surgery was
      66.2 microm. There was no difference between the clomethiazole and placebo group
      in the postoperative change in neuropsychological test scores. CONCLUSION:
      Clomethiazole did not improve cerebral outcome following coronary artery bypass
      surgery.

PMID- 12218526
TI  - Can the tomographic aspect characteristics of patients presenting with acute
      respiratory distress syndrome predict improvement in oxygenation-related response
      to the prone position?
AB  - BACKGROUND: In some patients with acute respiratory distress syndrome, the prone
      position is able to improve oxygenation, whereas in others it is not. It could be
      hypothesized that the more opacities that are present in dependent regions of the
      lung when the patient is in the supine position, the better the improvement in
      oxygenation is observed when the patients are turned prone. Therefore, we
      conducted a prospective study to identify computed tomographic scan aspects that
      could accurately predict who will respond to the prone position. METHODS: We
      included 46 patients with acute respiratory distress syndrome (31 responders and
      15 nonresponders). Computed tomographic scan was performed in the 6-h period
      preceding prone position. Blood gas analyses were performed before and at the end
      of the first 6-h period of prone position. RESULTS: Arterial oxygen partial
      pressure/fraction of inspired oxygen increased from 117 +/- 42 (mean +/- SD) in
      the supine position to 200 +/- 76 mmHg in the prone position (P < 0.001). There
      were 31 responders and 15 nonresponders. There was a vertebral predominance of
      the opacities (P < 0.0001). However, there was no difference between responders
      and nonresponders. When only the amount of consolidated lung located under the
      heart was evaluated, there was more consolidated tissue under the heart relative
      to total lung area in nonresponders than in responders (P = 0.01). CONCLUSIONS:
      There are no distinctive morphologic features in the pattern of lung disease
      measured by computed tomographic scanning performed with the patient in the
      supine position that can predict response to the prone position.

PMID- 12218525
TI  - Autonomic nervous system responses during sedative infusions of dexmedetomidine.
AB  - BACKGROUND: The purpose of this study was to determine the effects of
      dexmedetomidine on systemic and cardiac autonomic reflex responses during rest
      and during thermal stress. METHODS: Volunteers received either placebo or low- or
      high-dose dexmedetomidine (target plasma concentrations 0.3 or 0.6 ng/ml,
      respectively) infusions in a prospectively randomized, double-blinded crossover
      study design. After 1 h, baroreflex sensitivity was assessed, and then core body
      temperature was raised to the sweating threshold and then lowered to the
      shivering threshold. Plasma catecholamines and blood pressure were measured, and
      cardiac autonomic responses were assessed by analysis of heart rate variability.
      RESULTS: Compared with placebo, plasma norepinephrine concentrations, blood
      pressure, heart rate, and some heart rate variability measures were lower after 1
      h infusion of dexmedetomidine, but baroreflex responses did not differ
      significantly. Dexmedetomidine blunted the systemic and cardiac sympathetic
      effects of sweating observed during placebo infusion but had no effect on
      parasympathetic measures. Increases in blood pressure, and systemic
      catecholamines due to shivering were observed during placebo and dexmedetomidine,
      but these responses were less with dexmedetomidine. During shivering,
      dexmedetomidine infusion was associated with higher low-frequency and high
      frequency heart rate variability power but lower heart rate compared with the
      sweating threshold and with the control period, suggesting nonreciprocal cardiac
      autonomic responses. CONCLUSIONS: Infusion of dexmedetomidine results in
      compensated reductions in systemic sympathetic tone without changes in baroreflex
      sensitivity. Dexmedetomidine blunts heart rate and the systemic sympathetic
      activation due to sweating, but it is less effective in blunting cardiac
      sympathetic responses to shivering. During dexmedetomidine infusion, cardiac
      sympathetic and parasympathetic tone may have nonreciprocal changes during
      shivering.

PMID- 12218527
TI  - Comparing clinical productivity of anesthesiology groups.
AB  - BACKGROUND: Intergroup comparisons of clinical productivity are important for
      strategic planning and evaluation of clinical and business operations. However,
      in a preliminary study, comparisons of two anesthesiology groups using "per full
      time equivalent" measurements were confounded by different concurrencies or
      staffing ratios, whereas measurements based on "per operating room (OR) site,"
      "per case," and "billed American Society of Anesthesiologists (ASA) units per
      hour of care" permitted meaningful comparisons despite differing concurrencies.
      The purpose of this study was to determine whether these measurements would allow
      for meaningful comparisons when applied to multiple groups. METHODS: Annual
      totals of total ASA units (tASA), 15-min time units, and the number of cases
      billed, as well as the average number of daily anesthetizing sites (OR sites)
      staffed and the average number of anesthesiologists required to the staff sites,
      were collected from each group that participated. All anesthesia care billed with
      ASA units was included, except for obstetric care. Any clinical service not
      billed using ASA units was excluded. Productivity measurements (concurrency,
      tASA/OR site, hours billed per OR site per day, hours billed per case, tASA
      billed per hour of anesthesia care, and base units per case) were calculated.
      Median and range for all groups and for private-practice and academic groups were
      determined. RESULTS: Eleven private-practice and nine academic groups from 12
      states participated in the study. Productivity measurements that are influenced
      by duration of surgery (hours billed per case, tASA billed per hour of anesthesia
      care) differed significantly between groups, with private-practice groups having
      shorter duration than academic groups (median hours billed per case, 1.5 2.6,
      respectively). Although tASA/OR site measurements were similar in private
      practice and academic groups, academic groups worked significantly longer hours
      billed per OR site per day (median, 6.0 h 7.8, respectively) to achieve the same
      level of tASA/OR site. Hourly billing productivity (tASA billed per hour of
      anesthesia care) correlated highly with surgical duration (hours billed per
      case). CONCLUSION: This study demonstrates a method of comparing departmental
      clinical productivity between anesthesiology groups. Private-practice groups
      provided care for cases of shorter duration than academic groups. This difference
      was evident in several productivity measurements.

PMID- 12218528
TI  - Duration of anesthesia before muscle relaxant injection influences level of
      paralysis.
AB  - BACKGROUND: Dosage guidelines for muscle relaxants are based on dose-response
      studies, normally performed after several minutes of stable nitrous oxide (N O)
      opioid anesthesia. However, relaxants are used immediately after induction of
      anesthesia. The study was designed to determine the influence of the duration of
      anesthesia and N O on the onset time at the adductor pollicis (AP) and the
      corrugator supercilii (CS) muscles of maximum neuromuscular blockade after
      mivacurium. METHODS: After institutional approval and informed consent, patients
      were randomly allocated into three groups. Anesthesia was induced with alfentanil
      and propofol. Group A (n = 10) received mivacurium (0.1 mg/kg) immediately after
      loss of consciousness. Groups B (n = 10) and C (n = 10) received mivacurium after
      15 min of anesthesia with propofol alone (B) or propofol with N O (C). The evoked
      response to train-of-four stimulation was measured by acceleromyography at the AP
      and the CS. RESULTS: Maximum neuromuscular blockade (%T1, median [range]) was
      significantly less in group A than in groups B and C ( < 0.001) at both the AP
      (81 [47-90]; 90 [35-100]; 100 [93-100], respectively) and the CS (19 [5-63]; 68
      [61-100]; 89 [72-100], respectively). Maximum neuromuscular blockade was less in
      group B than in group C ( < 0.001) at the AP. Onset time of maximum neuromuscular
      blockade was not different between groups but was shorter at the CS than at the
      AP. CONCLUSIONS: Duration of anesthesia and N O before mivacurium injection
      affect intensity of neuromuscular blockade but not onset time. Neuromuscular
      blockade obtained at the AP after several minutes of stable anesthesia with N O
      is greater than immediately after induction. This explains in part the
      discrepancy between the measured ED and the intubating dose.

PMID- 12218529
TI  - Mivacurium arteriovenous gradient during steady state infusion in anesthetized
      patients.
AB  - BACKGROUND: Mivacurium and isomers undergo rapid hydrolysis by plasma
      cholinesterase. As this enzyme is largely distributed, it cannot be excluded that
      these isomers might undergo peripheral elimination. This hypothesis was
      investigated in patients by measuring the difference between arterial and venous
      concentrations under a constant-rate continuous infusion of mivacurium. METHODS:
      During propofol-remifentanil anesthesia, eight adult consenting patients received
      an intravenous bolus dose of 0.2 mg/kg mivacurium, followed by a constant
      infusion (3, 5, or 7 microg. kg. min ) into the brachial vein. One hour after
      starting the infusion, arterial (radial artery) and venous (contralateral
      brachial vein) blood samples were drawn simultaneously at 15-min intervals for 45
      min. Mivacurium isomers and metabolite plasma concentrations were determined by
      stereospecific high-performance liquid chromatography. Using the corresponding
      arterial and venous concentrations, the tissue extraction coefficient as well as
      total body clearance were calculated. RESULTS: During steady state conditions,
      the venous concentrations of the and isomers were 34 +/- 13% and 42 +/- 11% (mean
      +/- SD) lower than the corresponding arterial concentrations (P < 0.05),
      respectively. For the isomer, the difference between venous and arterial
      concentrations was 3 +/- 4% (P = 0.063). Total body clearances of the and isomers
      were greater when based on venous sampling (P < 0.05). CONCLUSION:
      Pharmacokinetic parameters derived from a constant infusion of mivacurium depend
      heavily on the sampling site (arterial or venous) for the rapidly hydrolyzed
      isomers. These results strongly suggest a significant metabolism of mivacurium
      within muscle tissue that may account for the large interpatient variability in
      response to mivacurium.

PMID- 12218530
TI  - Growth cone collapsing effect of lidocaine on DRG neurons is partially reversed
      by several neurotrophic factors.
AB  - BACKGROUND: Local anesthetics were suggested to have a potential for
      neurotoxicity in both clinical reports and laboratory experiments. Growing
      neurons have been shown to be susceptible to the toxic effects of local
      anesthetics in culture. These findings have generated the interest in factors
      that would rescue the neurons affected by the neurotoxicity of local anesthetics.
      METHODS: Primary cultured dorsal root ganglia were isolated from age-matched
      chick embryos and exposed to lidocaine. After 60 min of exposure, the culture
      media were replaced to wash out the lidocaine. Neurotrophic factors (NTFs)-brain
      derived neurotrophic factor, glial-derived neurotrophic factor, or neurotrophin 3
      were added to the replacement media to examine the capacity of these NTFs to
      support the reversibility of the lidocaine-induced growth cone collapse. The
      growth cone collapse assay was applied a quantitative method of assessment.
      RESULTS: When any of the three NTFs was added to the replacement media at a
      minimum concentration of 10 ng/ml, significantly high reversibility of the
      lidocaine-induced growth cone collapse was observed, especially at 48 h after
      washout (P < 0.05). At that time point, there was no significant difference
      between the values of growth cone collapse percentage in the cells that were
      exposed to lidocaine and supported by the NTFs after the washout, and the control
      cells (not exposed to lidocaine) (P > 0.05). CONCLUSION: The NTFs-brain-derived
      neurotrophic factor, glial-derived neurotrophic factor, and neurotrophin 3-were
      demonstrated to support the reversibility of lidocaine-induced growth cone
      collapse in primary cultured sensory neurons, an effect that was concentration-
      and time-dependent. Because similar effects were observed after tetracaine
      washout, the supporting effects of NTFs may not be specific to lidocaine.

PMID- 12218531
TI  - Peripheral nerve injury alters the alpha2 adrenoceptor subtype activated by
      clonidine for analgesia.
AB  - BACKGROUND: Previous studies suggest that the alpha adrenoceptor subtype is the
      target for spinally administered alpha -adrenergic agonists, clonidine, for pain
      relief. However, ST 91, a preferential alpha adrenoceptor subtype agonist,
      induces antinociception, and intrathecally administered alpha antisense
      oligodeoxynucleotide decreases antinociception induced by clonidine in the rat,
      suggesting non-A sites may be important as well. Therefore, the authors examined
      the subtype of alpha adrenoceptor activated by clonidine and ST 91 in normal rats
      and those with nerve injury-induced hypersensitivity. METHODS: The same
      mechanical stimulus was applied to normal rats and those following spinal nerve
      ligation, and the effect of intrathecal clonidine and ST 91 on withdrawal
      threshold to the stimulus was determined. To further examine subtypes, animals
      were spinally pretreated with vehicle, BRL 44408 (an alpha subtype-preferring
      antagonist), and ARC 239 (an alpha subtype-preferring antagonist). RESULTS: In
      normal animals, clonidine's effect was diminished by pretreatment with either
      antagonist, whereas ST 91's antinociceptive effect was solely blocked by
      pretreatment with ARC 239. In nerve-injured animals, the antihypersensitivity
      action of both clonidine and ST 91 was blocked by administration of ARC 239,
      whereas BRL 44408 was ineffective. CONCLUSIONS: These data agree with previous
      studies supporting that the alpha adrenoceptor is important to the
      antinociceptive effect of clonidine in normal animals. Nerve injury alters this
      and results in a total reliance on alpha adrenoceptors.

PMID- 12218532
TI  - Isoflurane alters angiotensin II-induced Ca2+ mobilization in aortic smooth
      muscle cells from hypertensive rats: implication of cytoskeleton.
AB  - BACKGROUND: Angiotensin II (AngII) is a potent vasoconstrictor involved in the
      short-term control of arterial blood pressure. Isoflurane was reported to
      decrease vascular tone through an alteration of vascular smooth muscle cell
      vasomotor response to several agonists, but its effect on AngII signaling is not
      known. On the other hand, vascular response to AngII is altered in hypertension.
      In this study, the authors tested the hypothesis that (1) isoflurane alters AngII
      induced intracellular Ca mobilization in aortic vascular smooth muscle cell from
      Wistar Kyoto and spontaneously hypertensive rats, and (2) this effect could be
      associated with an alteration of the organization of microtubular network,
      reported to be involved in AngII signaling. METHODS: The effect of 0.5-3%
      isoflurane was studied (1) on AngII (10 m)-induced intracellular Ca mobilization,
      intracellular Ca release from internal stores, and Ca influx in Fura-2 loaded
      cultured aortic vascular smooth muscle cell isolated from 6-week-old Wistar Kyoto
      and spontaneously hypertensive rats, using fluorescent imaging microscopy; and
      (2) on the organization of cytoskeletal elements, using immunofluorescence
      labeling. RESULTS: In both stains, isoflurane decreased in a concentration
      dependent manner AngII-induced intracellular Ca mobilization, Ca release from
      internal stores, and Ca influx through nifedipine-insensitive Ca channels. This
      effect occurred at a lower concentrations of isoflurane in Wistar Kyoto rats than
      in spontaneously hypertensive rats. In both strains, the effect of isoflurane on
      AngII- Ca mobilization was abolished by impairment with nocodazole, vinblastine,
      or paclitaxel of microtubules polymerization. Isoflurane directly altered tubular
      network organization in a concentration-dependent and reversible manner.
      CONCLUSIONS: Isoflurane decreased AngII-induced Ca mobilization at clinically
      relevant concentrations, suggesting that vascular response to AngII could be
      altered during isoflurane anesthesia. The hypertensive strain was found less
      sensitive than the normotensive one. In both strains, the isoflurane effect was
      associated with a microtubular network interaction.

PMID- 12218533
TI  - Effect of low isoflurane concentrations on the ventilation-perfusion distribution
      in injured canine lungs.
AB  - BACKGROUND: Rapid recovery and weaning from ventilatory support and
      cardiovascular stability are suggested advantages of isoflurane inhalation, in
      concentrations ranging from 0.1 to 0.6 vol%, for long-term sedation in mechanical
      ventilated patients. This study was designed to determine whether isoflurane in
      low concentrations impairs pulmonary gas exchange by increasing ventilation and
      perfusion (V(A)/Q) mismatch during lung injury. METHODS: Fourteen anesthetized
      dogs received in random order 0, 0.25, or 0.5 vol% end-tidal isoflurane before
      and after induction of lung injury with oleic acid. Gas exchange was assessed by
      blood gas analysis and by estimating the V(A)/Q distributions using the multiple
      inert gas elimination technique. RESULTS: Administration of oleic acid produced a
      lung injury with severe V(A)/Q mismatch and 38 +/- 4% intrapulmonary shunting of
      blood. During lung injury, isoflurane accounted for a dose-related increase in
      blood flow to shunt units from 38 +/- 4 to 42 +/- 3 (0.25 vol%) and 48 +/- 4%
      (0.5 vol%) (P < 0.05), dispersion pulmonary blood flow distribution from 0.94 +/-
      0.07 to 1.01 +/- 0.09 (0.25 vol%) and 1.11 +/- 0.11% (0.5 vol%) (P < 0.05), and a
      decrease in perfusion of normal V(A)/Q units from 58 +/- 5 to 55 +/- 4 (0.25
      vol%) and 50 +/- 4% (0.5 vol%) (P < 0.05) (mean +/- SE). Isoflurane decreased
      arterial oxygen partial pressure from 72 +/- 4 to 62 +/- 4 mmHg (0.25 vol%) and
      56 +/- 4 mmHg (0.5 vol%) (P < 0.05) and oxygen delivery from 573 +/- 21 to 529 +/
      19 ml. kg. min (0.25 vol%) and 505 +/- 22 ml. kg. min (0.5 vol%) (P < 0.05). Gas
      exchange, perfusion of shunt and normal V(A)/Q units, and pulmonary blood flow
      distribution was similar in absence of lung injury with and without isoflurane.
      Isoflurane 0.5 vol% lowered cardiac output during all conditions (P < 0.05).
      CONCLUSIONS Inhalation of low concentrations of isoflurane contributed to
      increased V(A)/Q mismatch and decreased systemic blood flow and oxygen delivery
      in mechanically ventilated animals with injured lungs.

PMID- 12218534
TI  - Intestinal and cerebral oxygenation during severe isovolemic hemodilution and
      subsequent hyperoxic ventilation in a pig model.
AB  - BACKGROUND: During severe isovolemic hemodilution, determination of critical
      hematocrit levels for the microvascular oxygenation of different organs might
      provide more insight into the effect of the redistribution of blood flow and
      oxygen delivery on the oxygenation of different organs. The effect of an
      increased amount of dissolved oxygen on tissue oxygenation during severely
      decreased hematocrit levels is not clear. METHODS: Fifteen anesthetized pigs were
      randomized between an experimental group (n = 10), in which severe isovolemic
      hemodilution was performed with 6% hydroxyethylstarch (1:1), and a time-matched
      control group (n = 5). Systemic, intestinal, and cerebral hemodynamic and
      oxygenation parameters were monitored. Microvascular oxygen partial pressure
      (muPo(2) ) was measured in the cerebral cortex and the intestinal serosa and
      mucosa, using the oxygen-dependent quenching of Pd-porphyrin phosphorescence. In
      the final phase of the experiment, fraction of inspired oxygen was increased to
      1.0. RESULTS: Hemodilution decreased hematocrit from 25.3 +/- 3.0 to 7.6 +/- 1.2%
      (mean +/- SD). Systemic and intestinal oxygen delivery fell with the onset of
      hemodilution; intestinal oxygen consumption deceased at a hematocrit of 9.9%,
      whereas the systemic oxygen consumption decreased at a hematocrit of 7.6%. During
      hemodilution, the intestinal and cerebral oxygen extraction ratios increased from
      baseline with 130 and 52%, respectively. Based on the intersection of the two
      best-fit regression lines, determined by a least sum of squares technique,
      similar critical hematocrit levels were found for systemic oxygen consumption and
      the cerebral and intestinal mucosa muPo(2); the intestinal serosa muPo(2)
      decreased at an earlier stage (P < 0.05). Hyperoxic ventilation improved the
      muPo(2) values but not systemic or intestinal oxygen consumption. CONCLUSIONS:
      During isovolemic hemodilution, the diminished oxygen supply was redistributed in
      favor of organs with a lower capacity to increase oxygen extraction. It is
      hypothesized that redirection of the oxygen supply within the intestines resulted
      in the preservation of oxygen consumption and mucosal muPo(2) compared with
      serosal muPo(2).

PMID- 12218535
TI  - Changes in regional ventilation after autologous blood clot pulmonary embolism.
AB  - BACKGROUND: Previous studies have suggested that pulmonary embolism (PE) and
      pulmonary artery occlusion result in a shift in alveolar ventilation away from
      unperfused regions. This study aimed to directly assess changes in regional
      specific ventilation (sV(A)) due to autologous blood clot PE using positron
      emission tomography. METHODS: Pulmonary embolism was created in six anesthetized,
      paralyzed, and mechanically ventilated sheep by injecting cylindrical clots of
      autologous blood (7 mm in diameter and height). Clots were progressively infused
      into a central vein until a stable mean pulmonary artery pressure between 30 and
      40 mmHg was achieved. A multislice positron emission tomography camera was used
      to image 15 contiguous, 6.5-mm-thick transverse cross-sections of the chest
      beginning just above the diaphragm. sV(A) from perfused regions (sV(A),(p)) was
      assessed as the ventilatory turnover rate of the tracer NN after central venous
      injection of NN-labeled saline. RESULTS: Pulmonary embolism obstructed flow to
      64% of imaged areas. Before PE, (sV(A),(p))was equivalent in areas that would
      remain perfused and those that would become embolized after PE (0.021 +/- 0.007
      0.021 +/- 0.006 s(-1); P = nonsignificant). After PE, sV(A),(p) of areas
      remaining perfused increased to 0.033 +/- 0.011 s (-1) (P < 0.005). This effect
      on regional sV(A),(p) could have been caused by active redistribution of
      sV(A),(p) or by a reduction in tracer concentration of perfused areas due to the
      dead space common to perfused and embolized regions. Model simulations indicated
      that the common dead-space effect could only explain a small part of the
      sV(A),(p) increase. CONCLUSIONS: An increase in sV(A),(p) of perfused regions
      occurs following PE with 7-mm autologous blood clots. This increase is most
      likely caused by a shift in ventilation away from embolized areas mediated by
      hypocapnic pneumoconstriction.

PMID- 12218536
TI  - Set positive end-expiratory pressure during protective ventilation affects lung
      injury.
AB  - BACKGROUND: The most appropriate method of determining positive end-expiratory
      pressure (PEEP) level during a lung protective ventilatory strategy has not been
      established. METHODS: In a lavage-injured sheep acute respiratory distress
      syndrome model, the authors compared the effects of three approaches to
      determining PEEP level after a recruitment maneuver: (1) 2 cm H(2)O above the
      lower inflection point on the inflation pressure-volume curve, (2) at the point
      of maximum curvature on the deflation pressure-volume curve, and (3) at the PEEP
      level that maintained target arterial oxygen partial pressure at a fraction of
      inspired oxygen of 0.5. RESULTS: Positive end-expiratory pressure set 2 cm H(2)O
      above the lower inflection point resulted in the least injury over the course of
      the study. PEEP based on adequate arterial oxygen partial pressure/fraction of
      inspired oxygen ratios had to be increased over time and resulted in higher mRNA
      levels for interleukin-8 and interleukin-1beta and greater tissue inflammation
      when compared with the other approaches. PEEP at the point of maximum curvature
      could not maintain eucapneia even at an increased ventilatory rate. CONCLUSION:
      Although generating higher plateau pressures, PEEP levels based on pressure
      volume curve analysis were more effective in maintaining gas exchange and
      minimizing injury than PEEP based on adequate oxygenation. PEEP at 2 cm H(2)O
      above the lower inflection point was most effective.

PMID- 12218537
TI  - Dexmedetomidine increases the cocaine seizure threshold in rats.
AB  - BACKGROUND: Central alpha adrenoceptors have been demonstrated to play an
      important role in the control of seizure activity; moreover, alpha adrenoceptors
      have been linked to electroencephalogram changes associated with cocaine. The
      purpose of this study was to determine if dexmedetomidine, a highly selective
      alpha -adrenoceptor agonist, alters the threshold for cocaine-induced seizure
      activity in rats. METHODS: Sprague-Dawley rats received a cocaine infusion (1.25
      mg x kg(-1) x min(-1)) followed 15 min later by the coinfusion of either
      dexmedetomidine (20-microg/kg intravenous bolus followed by an infusion of 1
      microg x kg(-1) x min(-1), CD group, n = 8) or an equal volume of saline (CS
      group, n = 8). Dexmedetomidine or saline were coinfused with cocaine until the
      onset of cocaine-induced seizures. Dopamine concentrations in the nucleus
      accumbens were measured by microdialysis paired with chromatography. To determine
      if changes in extracellular dopamine were related to the seizures, dopamine (1
      microm) was continuously delivered to the nucleus accumbens in a separate group
      (DACD group, n = 6) retrograde microdialysis. These rats then received an
      intravenous cocaine infusion followed by dexmedetomidine in the same manner as
      the CD group. RESULTS: Dexmedetomidine significantly increased the dose of
      cocaine necessary to produce seizures. Seizures occurred at 25.0 +/- 7.7 and 49.3
      +/- 14.8 min in CS and CD, respectively (P < 0.001). The ratio of the percent
      increase in accumbal dopamine to the cocaine dose at the onset of seizure
      activity was significantly lower in CD, 39.9 +/- 16.5, compared to CS, 82.2 +/-
      46.5 (P = 0.04). Intraaccumbal administration of dopamine prevented the effects
      of dexmedetomidine on the cocaine seizure threshold. CONCLUSIONS: These data
      suggest that dexmedetomidine increases the cocaine-induced seizure threshold
      possibly a mechanism related to the attenuation of the extracellular dopaminergic
      neurotransmitter response to cocaine.

PMID- 12218538
TI  - Carbon monoxide modulates endotoxin-induced microvascular leukocyte adhesion
      through platelet-dependent mechanisms.
AB  - BACKGROUND: Although precise mechanisms remain to be determined, recent studies
      show that heme oxygenase-1 (HO-1), providing endogenous carbon monoxide (CO) and
      bilirubin, serves as an antiinflammatory enzyme. This study aimed to clarify
      roles of CO in regulation of microvascular adhesion of platelets and leukocytes
      in endotoxemia. METHODS: Rats pretreated with or without hemin were anesthetized
      with pentobarbital and received continuous infusion of endotoxin. Platelets
      labeled with carboxyfluorescein diacetate succinimidyl ester and leukocyte
      behavior in mesenteric venules were visualized using intravital ultra-high-speed
      intensified fluorescence videomicroscopy. To examine the mechanisms for the
      effects of HO-1 on platelet and leukocyte behavior during endotoxemia, these
      studies were repeated with superfusion of either CO, bilirubin, or zinc
      protoporphyrine-IX. RESULTS: Endotoxin caused a marked depression of platelet
      velocity traversing along periendothelial regions, accompanied by augmented
      rolling and adhesion of leukocytes in venules. The endotoxin-elicited changes
      were attenuated by the HO-1 induction with hemin and restored by blockade of the
      enzyme activity with zinc protoporphyrine-IX, a potent inhibitor of HO-1. Such an
      inhibitory action of HO-1 on microvascular cell adhesion was reproduced by local
      superfusion of the buffer containing CO at micromolar concentrations. Such
      antiadhesive actions of CO on leukocytes disappeared under immunoneutralization
      of glycoprotein Ibalpha, an adhesion molecule against platelets, but not against
      leukocytes. Platelets isolated from hemin-treated rats increased their ability to
      generate CO and displayed lesser sensitivity of agonist-induced aggregation than
      those from controls. CONCLUSIONS: These results suggest that CO desensitizes
      endotoxin-induced adhesive responses of leukocytes, mainly through its ability to
      ameliorate platelet activation.

PMID- 12218539
TI  - Differential effects of bupivacaine on intracellular Ca2+ regulation: potential
      mechanisms of its myotoxicity.
AB  - BACKGROUND: Bupivacaine produces skeletal muscle damage in clinical
      concentrations. It has been suggested that this may be caused by an increased
      intracellular level of [Ca2+]. Therefore, the aim of this study was to
      investigate direct intracellular effects of bupivacaine on Ca2+ release from the
      sarcoplasmic reticulum (SR), on Ca2+ uptake into the SR, and on Ca2+ sensitivity
      of the contractile proteins. METHODS: Saponin skinned muscle fibers from the
      extensor digitorum longus muscle of BALB/c mice were examined according to a
      standardized procedure described previously. For the assessment of effects on
      Ca2+ uptake and release from the SR, bupivacaine was added to the loading
      solution and the release solution, respectively. Force transients and force
      decays were monitored, and the position of the curve relating relative isometric
      force free [Ca2+] was evaluated in the presence or absence of bupivacaine.
      RESULTS: Bupivacaine induces Ca2+ release from the SR. In addition, the Ca2+
      loading procedure is suppressed, resulting in smaller caffeine-induced force
      transients after loading in the presence of bupivacaine. The decay of caffeine
      induced force transients is reduced by bupivacaine, and it also shifts [Ca2+]
      force relation toward lower [Ca2+]. CONCLUSIONS: These data reveal that
      bupivacaine does not only induce Ca2+ release from the SR, but also inhibits Ca2+
      uptake by the SR, which is mainly regulated by SR Ca2+ adenosine triphosphatase
      activity. It also has a Ca2+ -sensitizing effect on the contractile proteins.
      These mechanisms result in increased intracellular [Ca2+] concentrations and may
      thus contribute to its pronounced skeletal muscle toxicity.

PMID- 12218540
TI  - Pentobarbital enhances GABAergic neurotransmission to cardiac parasympathetic
      neurons, which is prevented by expression of GABA(A) epsilon subunit.
AB  - BACKGROUND: Pentobarbital decreases the gain of the baroreceptor reflex on the
      order of 50%, and this blunting is caused nearly entirely by decreasing
      cardioinhibitory parasympathetic activity. The most likely site of action of
      pentobarbital is the gamma-aminobutyric acid type A (GABA(A)) receptor. The
      authors tested whether pentobarbital augments the inhibitory GABAergic
      neurotransmission to cardiac parasympathetic neurons, and whether expression of
      the GABA(A) epsilon subunit prevents this facilitation. METHODS: The authors used
      a novel approach to study the effect of pentobarbital on identified cardiac
      parasympathetic preganglionic neurons in rat brainstem slices. The cardiac
      parasympathetic neurons in the nucleus ambiguus were retrogradely prelabeled with
      a fluorescent tracer and were visually identified for patch clamp recording. The
      effects of pentobarbital on spontaneous GABAergic synaptic events were tested. An
      adenovirus was used to express the epsilon subunit of the GABA(A) receptor in
      cardiac parasympathetic neurons to examine whether this transfection alters
      pentobarbital-mediated changes in GABAergic neurotransmission. RESULTS:
      Pentobarbital increased the duration but not the frequency or amplitude of
      spontaneous GABAergic currents in cardiac parasympathetic neurons. Transfection
      of cardiac parasympathetic neurons with the epsilon subunit of the GABA(A)
      receptor prevented the pentobarbital-evoked facilitation of GABAergic currents.
      CONCLUSIONS: Pentobarbital, at clinically relevant concentrations, prolongs the
      duration of spontaneous inhibitory postsynaptic currents that impinge on cardiac
      parasympathetic neurons. This action would augment the inhibition of cardiac
      parasympathetic neurons, reduce parasympathetic cardioinhibitory activity, and
      increase heart rate. Expression of the GABA(A) receptor epsilon subunit in
      cardiac parasympathetic neurons renders the GABA receptors insensitive to
      pentobarbital.

PMID- 12218542
TI  - Conservative treatment of paraplegia after removal of an epidural catheter during
      low-molecular-weight heparin treatment.

PMID- 12218541
TI  - Increases in coronary collateral blood flow produced by sevoflurane are mediated
      by calcium-activated potassium (BKCa) channels in vivo.
AB  - BACKGROUND: Sevoflurane enhances coronary collateral blood flow independent of
      adenosine triphosphate-regulated potassium channels. The authors tested the
      hypothesis that this volatile anesthetic increases coronary collateral blood flow
      by either opening calcium-activated potassium channels or by directly stimulating
      nitric oxide synthesis in the canine coronary collateral circulation. METHODS:
      Twelve weeks after left anterior descending coronary artery ameroid constrictor
      implantation, barbiturate-anesthetized dogs (n = 22) were instrumented for
      measurement of hemodynamics and retrograde coronary flow. Dogs received
      sevoflurane ([0.5 and 1.0 minimum alveolar concentration [MAC]) during
      intracoronary infusions of drug vehicle (0.9% saline), the calcium-activated
      potassium channel antagonist iberiotoxin (13 microg/min), or the nitric oxide
      synthase inhibitor -nitro-l-arginine methyl ester (l-NAME, 300 microg/min).
      Retrograde coronary collateral blood flow was measured under baseline conditions,
      during and after administration of sevoflurane, and during intracoronary infusion
      of bradykinin. Data are mean +/- SEM. RESULTS: Sevoflurane increased (* < 0.05)
      retrograde coronary collateral blood flow (from 65 +/- 11 during control to 67 +/
      12* and 71 +/- 12* ml/min during 0.5 and 1.0 MAC, respectively). Iberiotoxin but
      not l-NAME attenuated these sevoflurane-induced increases in retrograde flow (6
      +/- 1*, 7 +/- 2*, and 3 +/- 2 ml/min during vehicle, l-NAME, and iberiotoxin,
      respectively). After discontinuation of sevoflurane, retrograde flow returned to
      baseline values in each group. Bradykinin increased retrograde flow in vehicle-
      (63 +/- 12 to 69 +/- 12* ml/min) but not in iberiotoxin- (61 +/- 7 to 62 +/- 5
      ml/min) or l-NAME-treated dogs (64 +/- 11 to 63 +/- 10 ml/min). CONCLUSIONS: The
      results demonstrate that sevoflurane increases coronary collateral blood flow, in
      part, through activation of calcium-activated potassium channels. This action
      occurs independent of nitric oxide synthesis.

PMID- 12218543
TI  - Spontaneous resolution of epidural hematoma after continuous epidural analgesia
      in a patient without bleeding tendency.

PMID- 12218544
TI  - Lidocaine-induced seizures in patients with history of epilepsy: effect of
      antiepileptic drugs.

PMID- 12218545
TI  - Severe bleeding following lumbar sympathetic blockade in two patients under
      medication with irreversible platelet aggregation inhibitors.

PMID- 12218546
TI  - Asynchronous independent intermittent positive pressure ventilation as a solution
      to refractory hypoxemia during chest surgery.

PMID- 12218547
TI  - Cardiac arrest on induction of anesthesia due to triple vessel coronary artery
      disease despite a "Negative" angiogram.

PMID- 12218548
TI  - Sniffing position: an easy way to carry out, not a glottic exposure guarantee.

PMID- 12218549
TI  - Comparison of intubating positions: the end point for position should be
      measured.

PMID- 12218550
TI  - There's more to intubation than laryngoscopy.

PMID- 12218551
TI  - The sniffing position.

PMID- 12218552
TI  - To "sniff" or not to "sniff": that is the question.

PMID- 12218553
TI  - A reconsideration of three axes alignment theory and sniffing position.

PMID- 12218554
TI  - Quality improvement in anesthesia for volunteer medical services abroad.

PMID- 12218555
TI  - Good outcome and volunteer medical services in developing countries are
      compatible.

PMID- 12218556
TI  - The BIS inverse problem and pharmacodynamics.

PMID- 12218557
TI  - A new cuff design prevents N2O diffusion.

PMID- 12218558
TI  - Kaolin-activated thromboelastography.

PMID- 12218559
TI  - Causes of elevated intraocular pressure during prone spine surgery.

PMID- 12218560
TI  - Thrombosis after deep hypothermic circulatory arrest with antifibrinolytic
      therapy: is factor V leiden the smoking gun?

PMID- 12218561
TI  - Hemodynamic stability after pediatric epidurals.

PMID- 12218563
TI  - Echo bib.

PMID- 12218562
TI  - Anesthesia respiratory circuit failure.

PMID- 12218564
TI  - ECMO resuscitation after massive pulmonary embolism during liver transplantation.

PMID- 12218565
TI  - T-wave abnormalities on preoperative electrocardiogram caused by "cardiac memory"
      related to intermittent preexcitation.

PMID- 12218566
TI  - Avoid luer connectors on blood pressure cuffs.

PMID- 12218567
TI  - Nonmalignant lesions in breast core needle biopsies: to excise or not to excise?
AB  - Large core needle biopsies using stereotactic mammography or ultrasound guidance
      are now commonly performed as the initial diagnostic approach to nonpalpable
      breast lesions. Although the subsequent management of patients with invasive
      cancer, ductal carcinoma in situ, and most benign lesions diagnosed on core
      needle biopsy specimens is straightforward, certain nonmalignant lesions pose
      dilemmas with regard to the most appropriate clinical management following core
      needle biopsy. The purpose of this article is to review the available data
      regarding several nonmalignant breast lesions, which when encountered in core
      needle biopsy specimens raise repeated management questions. These include
      atypical ductal hyperplasia, lobular neoplasia (atypical lobular hyperplasia and
      lobular carcinoma in situ), papillary lesions, radial scars, fibroepithelial
      lesions, mucocele-like lesions, and columnar cell lesions.

PMID- 12218568
TI  - Serous borderline tumors of the ovary: a long-term follow-up study of 137 cases,
      including 18 with a micropapillary pattern and 20 with microinvasion.
AB  - The natural history of serous borderline tumors (SBTs) of the ovary varies
      considerably. A group of investigators have proposed that a small subset of SBTs
      with a micropapillary architecture and an allegedly higher incidence of invasive
      peritoneal implants should be designated "micropapillary serous carcinomas."
      Based on the overall favorable prognosis of the nonmicropapillary SBTs, these
      investigators have recommended abandoning the borderline category of serous
      tumors, restricting them to benign (benign and typical SBTs) and malignant types;
      other investigators, however, are in favor of retaining the original grouping,
      designating borderline tumors with a micropapillary pattern as such instead of
      designating them carcinomas. We have reviewed the clinicopathologic records of
      137 patients with ovarian SBTs and obtained follow-up information on 106 of them
      ranging from 1 to 18 years (mean 7 years). Of the 21 patients with stage I tumors
      who had conservative surgical treatment, only two (9.5%) were subsequently found
      to have tumor in the contralateral ovary. Both were successfully managed by
      reoperation alone. Forty-five stage I patients had procedures that included
      bilateral oophorectomy, and two of them (4.4%) had a pelvic recurrence, which was
      fatal in one patient (whose tumor had been understaged) and occurred on multiple
      occasions in the other patient, finally transforming into invasive carcinoma;
      that patient survived. Of the 45 stage II-IV patients, only the six (13%) with
      invasive implants had an unfavorable outcome: three died of tumor (from 7 to 9.3
      years), and the other three were alive with progressive disease from 5 to 10
      years. Solid epithelial nests or small papillae surrounded by clefts and
      micropapillary architecture were found more often in invasive than in noninvasive
      implants. However, the only feature specifically associated with a poor outcome
      was obvious destructive invasion of the underlying tissue. Among the 137 SBTs, we
      identified 18 cases of serous borderline tumors with a micropapillary pattern
      (SBT-MP) (so-called "micropapillary carcinoma") and 20 cases of SBT with
      microinvasion (SBT-Minv) (three of which were also micropapillary). We compared
      the two groups of tumors with the remaining 102 cases of typical SBTs (which
      lacked micropapillary pattern and microinvasion). Of the 17 patients with SBT-MP
      and follow-up data, only the one patient with invasive implants had an
      unfavorable outcome; similarly, of the two patients with SBT-Minv and an
      unfavorable outcome, one had invasive implants and the other had been
      incompletely staged. SBTs have a very favorable prognosis, but complete surgical
      staging and prolonged follow-up are advised because pelvic recurrence and
      occasionally transformation to invasive carcinoma may occur. Designation of SBTs
      as "atypical proliferative tumors" is not recommended because it discourages
      complete surgical staging and follow-up. Advanced stage tumors with noninvasive
      implants are common, characteristically behave in a benign fashion, and can be
      safely treated conservatively. The rare SBTs associated with invasive implants
      are almost always fatal. SBT-MP and SBT-Minv are much closer in their biologic
      behavior to SBTs than to serous carcinomas. The micropapillary pattern alone does
      not imply an unfavorable prognosis; only micropapillary tumors associated with
      invasive implants behave aggressively.

PMID- 12218569
TI  - Micropapillary and cribriform patterns in ovarian serous tumors of low malignant
      potential: a study of 99 advanced stage cases.
AB  - Recently some investigators have proposed abandoning the term ovarian serous
      tumor of low malignant potential (SLMP) and dividing the tumors in this category
      into two new groups, micropapillary serous carcinoma and atypical proliferative
      serous tumor, based on the presence or absence of marked epithelial proliferation
      with a micropapillary or cribriform pattern (MP/CP). We reviewed 99 cases of
      advanced stage SLMP (FIGO stages II and III) to determine whether the presence or
      absence of MP/CP predicts the clinical course, thus justifying the proposed
      change in terminology. Eighteen cases of MP/CP and 81 cases of typical SLMP were
      identified. The patients with MP/CP ranged from 23 to 59 years of age at the time
      of diagnosis (median 35 years), whereas those with typical SLMP were 17 to 67
      years old (median 38 years). Bilateral ovarian involvement by SLMP was more
      frequent in the MP/CP cases, 13 of 18 (72%), as compared with the cases with
      typical SLMP, 46 of 81 (57%). There was a trend toward a greater frequency of
      invasive implants in MP/CP cases, 3 of 18 (17%) MP/CP versus 5 of 81 (6%)
      typical. The mean follow-up period was 125 months for MP/CP patients and 132
      months for the typical group. Differences in the frequency of recurrence and the
      progression-free survival between the groups were found to be significant.
      Fourteen (78%) of the MP/CP patients experienced either progression or recurrence
      of disease, whereas 25 (31%) of the typical SLMP patients had a recurrence (p =
      0.001). The progression-free survival ranged from 3 to 208 months for MP/CP
      patients versus 15 to 233 months for typical SLMP patients (p <0.0001). The
      majority of the recurrences in both groups were low-grade serous carcinoma, 11 of
      14 (79%) patients with progression/recurrence in the MP/CP group and 17 of 25
      (68%) patients with recurrence in the typical group. The overall survival of the
      patients in the two groups, however, was not significantly different. Five (28%)
      MP/CP patients and 12 (15%) patients with typical SLMP died of disease (p =
      0.11). All 17 of these patients developed serous carcinoma and died secondary to
      tumor progression. Four of eight (50%) patients with invasive implants and 13 of
      91 (14%) patients with noninvasive implants died of disease. Our findings of more
      frequent bilateral ovarian involvement, more frequent recurrence with a shorter
      progression-free interval, and the trend toward a more frequent association with
      invasive implants support the contention that MP/CP SLMP are a distinct subgroup
      of serous tumors. However, the overall survival of patients with MP/CP SLMP is
      similar to that of patients with typical SLMP and justifies the retention of
      tumors with MP/CP within the LMP category. Additionally, our long-term follow-up
      of patients with typical SLMP indicates that a number of these tumors do not
      follow a benign course and supports their continued designation as borderline
      neoplasms.

PMID- 12218570
TI  - Endometrial stromal sarcomas with unusual histologic features: a report of 24
      primary and metastatic tumors emphasizing fibroblastic and smooth muscle
      differentiation.
AB  - We report the clinicopathologic features of 24 uterine primary and metastatic
      endometrial stromal sarcomas with fibromyxoid features (ESS-F) and smooth muscle
      differentiation (ESS-SM) (endometrial stromal sarcoma variants). Two groups of
      tumors were retrieved from the surgical pathology files at Memorial Sloan
      Kettering Cancer Center: 1) gynecologic mesenchymal neoplasms with striking
      smooth muscle or fibroblastic differentiation that did not meet the clinical or
      histologic criteria for leiomyosarcoma or other established neoplasms containing
      smooth muscle; and 2) metastatic lesions showing ovoid and spindle cell
      morphology, involving lung, originally diagnosed as low-grade leiomyosarcoma, low
      grade smooth muscle neoplasm, intravenous leiomyomatosis, fibrous hamartoma, and
      benign metastasizing leiomyoma. We identified 12 patients with 30 tumors; 24 were
      available for review. The mean age was 51 years (range 21-74 years). Follow-up >1
      year was available for eight patients, with a mean time of 8.5 years. Each
      patient had a uterine primary and 10 experienced metastases. Mean time to
      recurrence was 6.8 years. Sites of metastasis included lung, retroperitoneum,
      right atrium/inferior vena cava, colon, and ovaries. No patient died of disease,
      but in many cases the follow-up period ended with the discovery of a metastasis.
      Four patients were originally diagnosed with endometrial stromal sarcoma, but
      other presenting diagnoses included benign metastasizing leiomyoma,
      fibroleiomyomatous tumor of lung, smooth muscle tumor of uncertain or low
      malignant potential, and intravascular leiomyomatosis. On review each patient had
      at least one tumor (primary and/or metastasis) that was determined to be an
      endometrial stromal sarcoma variant. Review diagnoses were as follows:
      endometrial stromal sarcoma (nonvariant), ESS-F, and ESS-SM. Eight of 10 primary
      tumors with available slides were endometrial stomal sarcoma variants (six ESS-F
      and two ESS-SM). When these variant features were present, they comprised between
      50% and 100% of the neoplasm. The variant histology tumors exhibited prominent
      spiral arterioles, perivascular edema, and stromal cell condensation around blood
      vessels. All metastases but one were variant tumors; eight were ESS-F and five
      were ESS-SM. Four metastases did not resemble the uterine primary. Desmin marked
      smooth muscle mostly but not specifically. h-Caldesmon marked smooth muscle
      exclusively. Endometrial stromal cells as well as some fibroblasts and smooth
      muscle cells expressed CD10. We conclude that the presence of even focal
      endometrial stromal differentiation in an invasive uterine mesenchymal lesion
      with a predominant low-grade smooth muscle, fibroblastic, and/or myxoid phenotype
      should permit classification as low-grade sarcoma-they should be considered
      endometrial stromal sarcomas.

PMID- 12218571
TI  - Can basal cells be seen in adenocarcinoma of the prostate?: an
      immunohistochemical study using high molecular weight cytokeratin (clone
      34betaE12) antibody.
AB  - Rare reports describe high molecular weight cytokeratin (clone 34betaE12)
      antibody cross-reactivity in scattered prostate carcinoma (PCa) cells, yet most
      often not in a true basal cell distribution. There are no data specifically
      describing 34betaE12 reactivity in basal cells in PCa. From August 10, 1995 to
      May 1, 2000, a total of 3198 consult prostate needle biopsies with PCa and a
      34betaE12 immunoperoxidase stain were reviewed at our institution. Thirty-six
      cases (1.1%), which on hematoxylin and eosin stain were unequivocal cancer, had
      at least focal 34betaE12 positivity in a basal cell distribution. Twenty-five had
      original diagnostic slides for review. All cancers were Gleason score 6. The mean
      number of cancer glands per case was 36.9 (10-108) with an average of 39% of
      glands (1-100%) showing 34betaE12 reactivity. Twenty-one cases had patchy
      staining in a basal cell distribution with one other case showing continuous
      staining. An additional case showed mainly tumor cell reactivity with rare basal
      cell staining. The final two cases showed a zonal staining pattern with small
      glands toward one side of the lesion showing basal cells [one with high grade
      prostatic intraepithelial neoplasia (HGPIN); one without HGPIN]. HGPIN was
      present in 16 of 25 (64%) cases adjacent to PCa. The mean number of HGPIN glands
      was 1.36 (1-6). In cases with HGPIN the mean ratio of cancer to HGPIN glands was
      6.8 (0.5-13.0). In 12 cases in which the lesion was still present on deeper
      sectioning, we were able to confirm in nine cases the presence of basal cells
      using antibodies to p63, another marker for prostatic basal cells. Four of the 25
      men underwent radical prostatectomy; all showed Gleason score 6 PCa. Three
      radical prostatectomies demonstrated 34betaE12 reactivity: two with patchy
      staining in a basal cell distribution and one with mainly tumor cell staining.
      Adjacent HGPIN was present in all three radical prostatectomy specimens. Rare
      lesions with the appearance of PCa show 34betaE12 staining in a basal cell
      distribution either from retention of basal cells by early invasive cancer or
      from HGPIN outpouching. The lack of adjacent HGPIN in some cases and the large
      ratio of small atypical glands to HGPIN glands argue against HGPIN outpouching as
      the sole explanation. In cases with adjacent HGPIN a comparison of the proximity
      and number of the small, atypical, infiltrative appearing glands to HGPIN is
      helpful. The diagnosis of PCa in the face of positive 34betaE12 basal cell
      staining should be made with extreme caution, only in the face of unequivocal
      cancer on the hematoxylin and eosin stain.

PMID- 12218572
TI  - Comparison of the basal cell-specific markers, 34betaE12 and p63, in the
      diagnosis of prostate cancer.
AB  - The basal cell-specific cytokeratin antibody (34betaE12) is widely used to aid in
      the diagnosis of cancer in challenging prostate needle biopsies (NBX) and
      transurethral resections of the prostate (TURP). Because prostate carcinoma (PCa)
      lacks basal cells, the absence of basal cell as determined by 34betaE12 can aid
      in the confirmation of a histologically suspicious lesion. However, false
      negative staining occurs because of patchy cytoplasmic staining, making a
      definitive diagnosis difficult. A recently identified basal cell marker p63, a
      p53 homologue, stains basal cell nuclei but not secretory cells. The aim of this
      study is to determine if the p63 antibody offers any clinically useful advantage
      over 34betaE12 in the diagnosis of challenging atypical prostate lesions. Ninety
      four cases, comprised of 25 consecutive prostate NBX and 2 TURP with an atypical
      suspicious focus, 55 NBX cases of histologically unequivocal PCa and 12 TURP
      specimen removed for benign prostate hyperplasia, were stained with the
      monoclonal antibodies 34betaE12 and 4A4 anti-p63. Basal cell staining intensity,
      percentage basal cell-positive glands in benign, malignant, and atypical foci,
      and number of benign glands not staining were evaluated for 34betaE12 and p63
      stains. A total of 67 prostate NBX cases, including one TURP, were diagnosed with
      PCa, 1 atypical small acinar proliferation, 10 benign, and 4 cases excluded
      because of lost tissue on step sections. None of the 67 PCa NBX cases
      demonstrated 34betaE12 or p63 immunoreactivity (100% specific). Whereas 57 of 108
      (53%) prostate NBX cores from 78 cases demonstrated a similar percentage of basal
      cell staining for both antibodies, 45 of 108 (41%) NBX cores demonstrated a
      higher percentage of p63 basal cell staining in benign glands. Only 6 of 108 NBX
      (6%) cores had a higher percentage of basal cell staining with 34betaE12
      (Wilcoxon signed rank test, p <0.0001). Lack of basal cell staining in more than
      two benign glands occurred in 25 of 108 (23%) and 10 of 108 (9%) prostate NBX
      cores stained with 34betaE12 and p63, respectively. In the vast majority of
      atypical cases, both 34betaE12 and p63 staining differences were not clinically
      significant, except in 2 of 27 (7%) cases p63 offered diagnostic utility beyond
      the 34betaE12 immunostain. p63 in these cases demonstrated discontinuous but
      strong staining in atypical glands and adjacent benign glands, whereas 34betaE12
      failed to stain optimally in this critical area. For 12 TURP cases the mean
      percentage basal cell positivity in benign glands was 75% and 95% for 34betaE12
      and p63, respectively (p = 0.006). Lack of basal cell staining in more than two
      glands occurred in 12 of 12 (100%) and 2 of 12 (17%) TURP specimens stained with
      34betaE12 and p63, respectively (p <0.0001). In summary, 34betaE12 and p63 are
      highly specific for basal cells and therefore are negative in areas of PCa. p63
      is more sensitive than 34betaE12 in staining benign basal cells, particularly for
      TURP specimens, offering slight advantage over 34betaE12 in diagnostically
      challenging cases. p63 may be used as an alternative to 34betaE12 stain for
      difficult prostate lesions.

PMID- 12218573
TI  - P504S/alpha-methylacyl-CoA racemase: a useful marker for diagnosis of small foci
      of prostatic carcinoma on needle biopsy.
AB  - Establishing a definitive diagnosis of malignancy in prostate needle biopsies
      with very small foci of adenocarcinoma is a major diagnostic challenge for
      surgical pathologists. A positive diagnostic marker specific for prostatic
      adenocarcinoma may enhance our ability to detect limited prostate cancer and
      reduce errors in diagnosis. P504S, also known as alpha-methylacyl-CoA racemase,
      recently identified by cDNA subtraction and microarray technology, might serve as
      such a specific marker because it has been demonstrated to be highly expressed in
      prostatic adenocarcinoma, but not in benign prostatic glands. However, whether
      small foci of carcinoma can be reliably detected by this marker is a crucial
      question for its clinical application. The aim of this study was to assess the
      utility of P504S immunohistochemistry in detecting small amounts of prostate
      cancer in prostate needle biopsies. A total of 142 prostate needle biopsies,
      including 73 cases with a small focus of prostatic adenocarcinoma (</=1 mm) and
      69 benign prostates, were examined by using immunohistochemistry for P504S and
      high molecular weight cytokeratin (34betaE12). P504S immunoreactivity was found
      in 69 of 73 cases (94.5%) of carcinoma but not in any benign prostates (0 of 69)
      or benign glands adjacent to malignant glands. The 34betaE12 immunostaining
      confirmed the absence of basal cells in the focus of carcinoma in all 73 cases.
      The high specificity and sensitivity of P504S in the detection of minimal
      prostatic adenocarcinoma indicated its potential diagnostic value in clinical
      practice. Using a combination of P504S and 34betaE12 can help the diagnosis of
      limited prostatic adenocarcinoma on needle biopsy.

PMID- 12218574
TI  - Sclerosing rhabdomyosarcoma in adults: report of four cases of a hyalinizing,
      matrix-rich variant of rhabdomyosarcoma that may be confused with osteosarcoma,
      chondrosarcoma, or angiosarcoma.
AB  - Rhabdomyosarcomas (RMSs) are classified into embryonal (ERMS), alveolar (ARMS),
      and pleomorphic (PRMS) subtypes. ERMS, including botryoid variants, typically
      occurs in young children, ARMS typically occurs in older children and young
      adults, and PRMS occurs in older adults. Although ARMSs show thin fibrous bands
      separating nests of cells, abundant extracellular matrix production is rare in
      RMS. In the course of reviewing hyalinizing sarcomas we discovered a distinctive
      RMS in adults that closely mimicked osteosarcoma or chondrosarcoma because of the
      extensive matrix production. Four RMSs with hyalinized matrix were retrieved from
      our files. These cases were evaluated with respect to patient age and sex, tumor
      site and size, growth pattern, nuclear grade, cellularity, mitotic figures/20
      high power fields, vascular invasion, necrosis, the presence of rhabdomyoblasts,
      multinucleated cells, and alveolar growth pattern. Immunohistochemistry for
      desmin, myogenin, MyoD1, actin, cytokeratin, S-100 protein, collagen II, and CD99
      was performed. Reverse transcriptase polymerase chain reaction for the ARMS
      associated PAX3/FKHR and PAX7/PKHF was also performed on three cases. The cases
      involved the forearm, hand, orbit, and nasopharynx of a 40-year-old woman, a 50
      year-old man, an 18-year-old man, and a 21-year-old man, respectively. The tumors
      ranged from 3.7 to 8 cm and consisted of lobules and infiltrating cords of small
      round malignant cells embedded in a densely hyalinized matrix having both a
      chondroid and osteoid-like appearance. No definite lacunae or matrix
      calcification was present. An alveolar pattern was only present focally, and
      tumor giant cells were not present. One case had a single focus of
      rhabdomyoblastic differentiation with strap cells. Mitotic activity was >20
      mitotic figures/20 high power fields in three of four cases.
      Immunohistochemically, one case strongly expressed desmin, whereas three cases
      expressed it focally, with a dot-like pattern. Myogenin was only focally
      positive, but MyoD1 was present in nearly every cell of each case. Two cases
      expressed actin and one expressed CD99. No case expressed cytokeratin, S-100
      protein, or collagen II. Only one case contained adequate RNA for reverse
      transcriptase polymerase chain reaction, and this case was negative for the ARMS
      associated gene fusions. Follow-up showed one patient to be dead of metastatic
      disease at 60 months despite intensive therapy, another patient to be disease
      free at 26 months, and the third patient to be disease free at 5 months. The
      fourth case is recent. These cases are a distinctive-appearing rhabdomyosarcoma
      easily mistaken for variants of chondrosarcoma, osteosarcoma, or even sclerosing
      epithelioid fibrosarcoma because of their hyalinizing appearance compounded by
      their typically focal and dot-like desmin expression. These four cases are
      essentially identical to the three unusual RMSs recently reported by Mentzel and
      Katenkamp as "sclerosing, pseudovascular rhabdomyosarcoma in adults." Although
      the focal alveolar architecture and the primitive cytologic appearance of these
      hyalinizing RMS suggest a relationship with ARMS, the presence of abundant strap
      cells in one case, the predominant expression of MyoD1 rather than myogenin, and
      the absence of ARMS-associated fusions genes point more strongly toward a variant
      of ERMS. However, the late adult age in two cases is unusual for both EMRS and
      ARMS, suggesting that sclerosing RMS may prove to be a distinct subtype of RMS.
      Study of additional cases will be necessary to more fully elucidate its place
      among RMS and its prognostic significance.

PMID- 12218575
TI  - Small cell lung carcinoma (SCLC): a clinicopathologic study of 100 cases with
      surgical specimens.
AB  - Separation of small cell lung carcinoma (SCLC) from nonsmall cell lung carcinoma
      (NSCLC) is a critical distinction to be made in the diagnosis of lung cancer.
      However, the diagnosis of SCLC is most commonly made on small biopsies and
      cytologic specimens, and practicing pathologists may not be familiar with all its
      morphologic guises and frequent combination with NSCLC elements, which may be
      seen in larger specimens. Following the most recent WHO classification of lung
      tumors and with the hope of identifying prognostic markers, we examined in detail
      the histology of 100 surgical biopsies or resections with a diagnosis of SCLC
      from the AFIP and pathology panel of the International Association for the Study
      of Lung Cancer (IASLC). Multiple clinical and histologic features were studied by
      Kaplan-Meier analysis. Neuroendocrine architectural patterns, including nested
      and trabecular growth, with peripheral palisading and rosette formation were
      common in SCLC. Necrosis and apoptotic debris was prominent in all cases, but
      crush artifact was infrequent. Cell size in surgical biopsy specimens appears
      larger than in bronchoscopic biopsy specimens and occasional cells may show
      prominent nucleoli and vesicular nuclear chromatin, but this does not preclude
      the diagnosis of SCLC. A high percentage of cases (28%) showed combinations with
      NSCLC, with large cell carcinoma the most common, followed by adenocarcinoma and
      squamous cell carcinoma. Because of the frequency of a few scattered large cells
      in SCLC, we arbitrarily recommend that at least 10% of the tumor show large cell
      carcinoma before subclassification as combined SC/LC. However, combined SCLC is
      easily recognized if the additional component consists of other NSCLC subtypes
      such as adenocarcinoma or squamous cell carcinoma, so no percentage requirement
      is needed. Stage remained the only predictor of prognosis.

PMID- 12218576
TI  - 'Black Spots' and hyaline pleural plaques on the parietal pleura of 150 urban
      necropsy cases.
AB  - The absence of any direct connection between the lung and the parietal pleura
      raises questions about the mechanisms of pleural migration and retention of
      inhaled particles. It has been suggested that specific areas of parietal pleura
      absorb and retain inorganic particles from the pleural space, including carbon
      pigments and asbestos fibers, and could be starting points for pathologic changes
      induced by mineral fibers. These particle-collecting structures have been called
      "black spots." To study their distribution, macroscopic appearance, and possible
      relationship with pleural plaques, the parietal pleura of 150 consecutive
      necropsies of urban dwellers (mean age 67.7 +/- 12.9 years) were examined. The
      size and intensity of spots were scored and recorded on a computer scheme
      together with information of the presence of pleural plaques. Black spots were
      observed in 92.7% of the cases. They were mainly located in the lower costal and
      diaphragmatic zones and could correspond to the anatomic distribution of
      structures involved in pleural cavity clearance. Scores correlated with sex and
      age. There was no relationship between the predominant locations of black spots
      and hyaline pleural plaques.

PMID- 12218577
TI  - Histopathology of the gastroesophageal junction: a study on 36 operation
      specimens.
AB  - The entire gastroesophageal junction of 36 patients who had been operated for
      squamous cell carcinoma of the upper or middle esophagus was examined.
      Hematoxylin and eosin-stained slides were evaluated by two pathologists for the
      following histologic details: minimal and maximal length of cardiac mucosa (CM)
      and oxyntocardiac mucosa (OCM, mixture of cardiac and fundic glands), degree of
      inflammation in CM and OCM, and presence of intestinal metaplasia or pancreatic
      metaplasia. Sections of gastric corpus mucosa were evaluated for the presence of
      gastritis and infection; sections of esophageal squamous epithelium were
      evaluated for the presence of reflux esophagitis. CM was present in the entire
      circumference of the gastroesophageal junction in 20 cases, in parts of the
      circumference in 15 cases, and entirely absent in one case. The maximal length
      per case ranged between 1 and 15 mm (median 5 mm). OCM was circumferentially
      present in 22 cases and partially present in 14 cases. The maximal length ranged
      between 2 and 24 mm (median 7 mm). Locations of CM/OCM over submucosal esophageal
      glands or squamous epithelium-lined ducts, both indicating a location in the
      esophagus, were found in eight cases (22%) and in four cases (11%), respectively.
      In 18 cases (50%) intestinal metaplasia was present in CM/OCM; pancreatic
      metaplasia was found in 22 cases (61%). A statistically not significant trend for
      increase of minimal length of CM, OCM, and the sum of both was found in the
      presence of gastroesophageal reflux disease. Neither the presence of intestinal
      metaplasia nor of pancreatic metaplasia in CM/OCM was correlated with
      gastroesophageal reflux disease. In conclusion, the high variability in length,
      the frequent occurrence of intestinal metaplasia and pancreatic metaplasia, and
      the frequent extension into the esophagus suggest that CM/OCM is a dynamic
      structure that probably mirrors the influence of underlying gastroesophageal
      diseases. Because of the short length and incomplete circumferential extension of
      CM/OCM, future endoscopic-bioptic investigations will probably have to be based
      on more extensive sampling of the gastroesophageal junction.

PMID- 12218578
TI  - Cytokeratin expression in adenocarcinomas of the esophagogastric junction: a
      comparative study of adenocarcinomas of the distal esophagus and of the proximal
      stomach.
AB  - Adenocarcinomas of the esophagogastric junction form a heterogeneous group of
      tumors. We aimed to evaluate the value of the expression pattern of cytokeratins
      7, 19, and 20 for their diagnosis and classification. A total of 85 cases of
      adenocarcinoma of the distal esophagus and 67 cases of adenocarcinoma of the
      proximal stomach, defined on strict topographical criteria, were investigated.
      About 90% of the adenocarcinomas of distal esophagus were positive for
      cytokeratins 7 and 19, in contrast to <45% of the adenocarcinomas of proximal
      stomach (p <0.01); 17.6% of the adenocarcinomas of the distal esophagus and 55.2%
      of the adenocarcinomas of the proximal stomach expressed cytokeratin 20 (p
      <0.01); and 74.1% of the adenocarcinomas of the distal esophagus and 23.8% of the
      adenocarcinomas of the proximal stomach had a CK7+/CK20- immunophenotype (p
      <0.01). In intestinal-type tumors a CK7+/CK20- immunophenotype had a sensitivity
      of 76.5%, a specificity of 84.5%, and a predictive positive value of 87.3% for
      the diagnosis of adenocarcinoma of the distal esophagus. Cytokeratin patterns are
      different in adenocarcinomas of the distal esophagus and in adenocarcinomas of
      the proximal stomach. A CK7+/CK20- pattern is highly suggestive of an esophageal
      origin and may be helpful for the correct classification of esophagogastric
      adenocarcinomas.

PMID- 12218579
TI  - Clinical significance of performing immunohistochemistry on cases with a previous
      diagnosis of cancer coming to a national comprehensive cancer center for
      treatment or second opinion.
AB  - Immunohistochemistry (IHC) is an important adjunctive test in diagnostic surgical
      pathology. We studied the clinical significance and outcomes in performing IHC on
      cases with a previous diagnosis of cancer who are coming to the Fox Chase Cancer
      Center (FCCC), a National Cancer Institute designated National Comprehensive
      Cancer Center (NCCC), for treatment and/or second opinion. We reviewed all the
      outside surgical pathology slide review cases seen at the FCCC for 1998 and 1999
      in which IHC was performed. Cases were divided into the following: confirmation
      of outside diagnoses without and with prior IHC performed by the outside
      institution (groups A and B, respectively) and cases with a significant change in
      diagnosis without and with prior IHC performed by the outside institution (groups
      C and D, respectively). During 1998 and 1999, 6678 slide review cases were
      reviewed at the FCCC with an overall significant change in diagnosis in 213 cases
      (3.2%). IHC was performed on 186 of 6678 (2.7%) slide review cases with
      confirmation of the outside diagnosis in 152 (81.7%) cases and a significant
      change in diagnosis in 34 (18.3%) cases. Patient follow-up was obtained in 32 of
      34 (94.1%) cases with a significant change in diagnosis (groups C and D), which
      confirmed the correctness of our diagnosis in 26 of 27 cases (96%; in five cases
      follow-up was inconclusive). We repeated the identical antibodies performed by
      the outside institutions in group D (37 antibodies) and group B (133 antibodies)
      with different results in 48.6% and 13.5%, respectively (overall nonconcordance
      21.2%). In group D additional antibody tests beyond that performed by the outside
      institution were needed in 88.8% of cases to make a change of diagnosis. In the
      setting of a NCCC, reperforming and/or performing IHC on cases with a previous
      diagnosis of cancer is not a duplication of effort or misuse of resources.
      Repeating and/or performing IHC in this setting is important in the care and
      management of patients with cancer.

PMID- 12218580
TI  - A case of clear cell adenocarcinoma of the mullerian duct in persistent mullerian
      duct syndrome: the first reported case.
AB  - We report a case of a 67-year-old man with clear cell adenocarcinoma of the
      remnant uterus in persistent Mullerian duct syndrome. He had a normal penis,
      urethra, and scrotum, and there was also a vagina and uterus. He died in a
      traffic accident, and clear cell adenocarcinoma was discovered incidentally at
      autopsy. Clear cell adenocarcinoma of the remnant uterus metastasized to the
      retroperitoneal lymph nodes and bilateral lungs. Persistent Mullerian duct
      syndrome is characterized by the persistence of Mullerian derivatives in
      otherwise normally virilized males. A variety of germ cell tumors of the testis
      have been reported in association with persistent Mullerian duct syndrome.
      However, no malignant change of the persistent Mullerian duct structures has been
      reported. This represents the first reported case of malignant change of the
      persistent Mullerian duct structures in persistent Mullerian duct syndrome.

PMID- 12218581
TI  - Multinucleated giant cells in plantar fibromatosis.

PMID- 12218582
TI  - Review of 'outside' pathology before treatment should be mandatory.

PMID- 12218583
TI  - High-density tissue microarray.

PMID- 12218584
TI  - Fasciola hepatica and parasitic eosinophilic granuloma of the Liver.

PMID- 12218585
TI  - Comments From the Editor-in-Chief.

PMID- 12218586
TI  - Clinical trials in childhood acute lymphoblastic leukemia: a common prognostic
      classification and a common induction therapy are now warranted.

PMID- 12218587
TI  - Response to Donadieu and Hill "Clinical trials in childhood acute lymphoblastic
      leukemia: a common prognostic classification and a common induction therapy are
      now warranted".

PMID- 12218588
TI  - Thoracoscopic surgery in childhood cancer.
AB  - PURPOSE: Recent advances in minimally invasive surgery, especially thoracoscopy,
      have allowed many new applications in children. The authors' purpose was to
      review their experience with thoracoscopic surgery in childhood cancer. They
      hypothesized that thoracoscopy can be efficacious, safe, and cost-effective and
      has the potential to change the way we care for children with cancer. PATIENTS
      AND METHODS: The authors reviewed their thoracoscopic experience of the past 7
      years. Thoracoscopic procedures performed included biopsy and resection of
      masses, resection of lung nodules, biopsy of infiltrates, and lobectomy. Some
      resections required conversion to open thoracotomy. RESULTS: Sixty-three
      thoracoscopic procedures were performed on 52 children; 8 required conversion to
      open thoracotomy and 55 were completed by thoracoscopy alone. The overall success
      rate was 98.4%. There were three complications and no deaths. The mean surgery
      time was 1.2 hours, mean length of hospital stay was 1.9 days, and mean number of
      chest tube days was 0.7. CONCLUSIONS: Thoracoscopic surgery in the treatment of
      children with cancer can be efficacious, safe, and cost-effective. Mediastinal
      masses can usually be biopsied and resected by thoracoscopy alone. Conversion to
      open thoracotomy for a more complete resection can be safely accomplished if
      needed. Thoracoscopic removal of lung nodules allows more accurate staging and
      early initiation of chemotherapy. Thoracoscopic biopsy of lung infiltrates can be
      safely performed in intubated, critically ill children and changed the treatment
      in all of these patients. Surgery time and days in hospital were decreased
      compared with historical thoracotomy data.

PMID- 12218589
TI  - Invasion of the cardiovascular system in childhood malignant hepatic tumors.
AB  - PURPOSE: To evaluate the utility of transthoracic echocardiography for the early
      detection of subclinical cardiac metastasis in childhood malignant hepatic
      tumors. PATIENTS AND METHODS: From April 1995 until February 2000, 12 consecutive
      children with malignant hepatic tumor were enrolled in this study. To determine
      the degree of invasion of the cardiovascular system, transthoracic
      echocardiography was performed for all patients at the time of initial diagnosis
      and also at subsequent follow-up investigations every 6 months until the patient
      was deemed to be disease-free, or until the patient died. RESULTS: There were
      seven patients diagnosed with hepatocellular carcinoma (six boys, one girl) and
      five patients diagnosed with hepatoblastoma (three boys, two girls). Most tumors
      were multiple (7/12) and involved both lobes of the liver (7/12). Inferior vena
      cava thrombi were observed in four patients. Three patients exhibited
      intracardiac tumor metastasis, and lung metastasis was noted in four patients.
      Lung metastasis was significantly more common in children with cardiovascular
      involvement (4/4) compared with those without (0/8). The ages of the patient,
      levels of alpha-fetoprotein, and types of tumor did not differ between the two
      groups. CONCLUSIONS: Echocardiography may be useful for the early detection of
      cardiovascular metastases of malignant hepatic tumors in children; this was the
      case for 33% of the patients in this series. The frequent occurrence of
      cardiovascular tumor involvement and the high degree of association between lung
      metastasis and cardiovascular involvement observed in this small series suggest
      that transthoracic echocardiography should be studied prospectively in a large
      series of children with hepatic tumors.

PMID- 12218591
TI  - Differential susceptibility of pediatric sarcoma cells to oncolysis by
      conditionally replication-competent herpes simplex viruses.
AB  - PURPOSE: Attenuated viruses derived from herpes simplex virus (HSV) type 1 that
      kill tumor cells (oncolysis) are currently in clinical trials for selected
      cancers, primarily carcinomas and gliomas. The authors sought to determine if
      pediatric sarcoma cells are also sensitive to HSV-mediated oncolysis. MATERIALS
      AND METHODS: The authors tested a panel of ten cell lines derived from
      rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, and a secondary malignant fibrous
      histiocytoma for survival after exposure to attenuated HSV vectors. The viruses
      used included NV1020, haploid for the neurovirulence gene, and G207, deleted for
      both and ribonucleotide reductase but expressing the beta-galactosidase reporter
      gene. G207 transduction was determined by measuring beta-galactosidase
      expression. RESULTS: Sarcoma cells differed in their sensitivity to viral
      oncolysis but were relatively consistent by histologic type. Rhabdomyosarcoma and
      malignant fibrous histiocytoma cells were most sensitive while osteosarcoma cells
      were intermediately sensitive to oncolysis by both HSV recombinants. Although
      Ewing sarcoma cells showed efficient viral entry and gene transfer, these cells
      were the least susceptible to oncolysis by HSV. CONCLUSIONS: Conditionally
      replication-competent HSV-derived vectors may be useful for the treatment of
      rhabdomyosarcoma and osteosarcoma, but may not be as efficacious for treating
      Ewing sarcoma until the mechanism of resistance is defined and circumvented.

PMID- 12218590
TI  - Treatment of metastatic osteosarcoma with the somatostatin analog OncoLar:
      significant reduction of insulin-like growth factor-1 serum levels.
AB  - BACKGROUND: Insulin-like growth factor-1 (IGF-1) has been implicated in the
      growth and/or metastasis of osteosarcoma (OS) and chondrosarcoma based on in
      vitro and experimental animal studies. STUDY PURPOSE: To determine the degree of
      growth hormone (GH), IGF-1 axis blockade, toxicities, and antitumor effect of
      OncoLar (ONC) (Novartis, East Hanover, NJ, U.S.A.) in OS. DESIGN/METHODS: A phase
      1 study with ONC enrolled 21 OS patients (median age 19 y) in four cohorts: ONC
      60 mg or 90 mg intramuscularly every 4 weeks with/without tamoxifen (TAM) 20 mg
      oral daily. RESULTS: There were no dose-limiting toxicities. Nineteen percent of
      patients had grade III drug-related toxicities including: 62% of patients showed
      progressive disease after two courses (8 wk). Nineteen percent received four
      courses. No clinical responses were observed. At weeks two and eight of therapy,
      IGF-1 serum levels dropped 46% ( < 0.0001, n = 21) and 53% ( = 0.003, n = 10).
      The difference of the area under the curve (AUC) minus baseline AUC (DeltaAUC)
      for arginine-stimulated GH serum levels at week two was lower than baseline ( <
      0.01). At weeks two and eight, GH peak values were lower than baseline ( < 0.0001
      and = 0.002, respectively). CONCLUSIONS: A long-acting somatostatin analog was
      able to lower IGF-1 levels of OS patients. IGF-BP-3 and GH were only transiently
      reduced. Although ONC was well tolerated, no sustained clinical responses were
      observed. The pathophysiology of serum versus tissue concentrations of IGF-1 as
      well as the interplay of IGFs, IGF-binding proteins, and other growth factors and
      cytokines in osteosarcoma warrants further investigation. A better understanding
      of these processes should lead to a more effective exploitation of these pathways
      for the targeted therapy of OS.

PMID- 12218592
TI  - Clinical stage I nonseminomatous germ cell tumors of the testis in childhood and
      adolescence: an analysis of 31 cases.
AB  - A 20-year single-institution experience of clinical stage I nonseminomatous germ
      cell tumors of the testis (NSGCTT) in childhood and adolescents was reviewed in
      relation to clinical characteristics, treatment modalities, and survival. Thirty
      one patients with clinical stage I NSGCTT were seen between 1980 and 2000: 14
      children and 17 adolescents. Yolk sac tumors and/or teratomas occurred in the
      children, whereas mixed histologies, including embryonal carcinoma, were
      predominant in the adolescents. After orchiectomy, the children were assigned to
      surveillance and the adolescents to active treatment: 16 underwent
      retroperitoneal lymph node dissection (RPLND) and 1 had adjuvant cisplatin-based
      chemotherapy because of a high-risk histology. Three of the 14 children (21.4%)
      relapsed 3, 7, and 8 months after orchiectomy: all 3 had yolk sac tumors and
      presented with increased alpha-fetoprotein levels. No patients had
      retroperitoneal relapse; two recurred locally and one in the lung. All three
      children were treated with cisplatin-based chemotherapy with or without surgery.
      Among the 16 adolescents undergoing RPLND, 4 (25%) had nodal metastases. Three of
      the 12 patients (25%) who had negative nodes at RPLND relapsed in the lung 3, 7,
      and 8 months after RPLND. All were treated with cisplatin-based chemotherapy with
      or without surgery. Five-year relapse-free and overall survival rates for the
      whole series were 80.6% and 100%, respectively. This series enabled the authors
      to pinpoint several important aspects of stage I NSGCTT in children and
      adolescents. In particular, almost all the childhood cases had the same yolk sac
      tumor histology, the children tended to have localized disease, and an increased
      alpha-fetoprotein level had a very high predictive value, suggesting that follow
      up should include AFP measurements. A conservative approach is the best option in
      children, while adolescent NSGCTT behaves like the adult disease and management
      must include similar treatment strategies.

PMID- 12218593
TI  - Kasabach-merritt phenomenon: a retrospective study of treatment with vincristine.
AB  - PURPOSE: Kasabach-Merritt phenomenon (KMP) is characterized by profound
      thrombocytopenia, microangiopathic hemolytic anemia, a consumptive coagulopathy,
      and an enlarging vascular lesion. The syndrome develops in infancy and is
      associated with a high morbidity and mortality rate. The purpose of this study
      was to assess the effectiveness of vincristine in the treatment of KMP. METHODS:
      We retrospectively reviewed the clinical and laboratory data of 15 patients with
      KMP treated with vincristine at 9 institutions across the United States, South
      America, and Europe. RESULTS: All 15 patients had profound thrombocytopenia and
      consumption of fibrinogen at presentation. Ten patients had biopsies of their
      lesions, and results included five (33.3%) kaposiform hemangioendotheliomas,
      three (20%) tufted angiomas, one lesion (6.7%) with features of both kaposiform
      hemangioendothelioma and tufted angioma, and one (6.7%) unclassified vascular
      tumor. All 15 patients had an increase in platelet count of at least 20,000 with
      an average response time of 4.0 weeks after initiation of vincristine therapy.
      Thirteen patients had an increase in fibrinogen level of 50 mg/dL with an average
      response time of 3.4 weeks. In 13 patients there was a significant decrease in
      the size of the vascular lesion. The average duration of treatment was 21.5 (+/
      12.6) weeks. Four patients (26%) relapsed. All four were successfully treated
      with a second course of vincristine. Complications included one patient with
      abdominal pain, one patient with transient loss of deep tendon reflexes, and one
      patient with irritability. CONCLUSION: Vincristine presents a safe and sometimes
      effective treatment option in the management of KMP.

PMID- 12218594
TI  - Vitamin B6 status of children with sickle cell disease.
AB  - PURPOSE: In vitro, vitamin B(6) has antisickling properties, but the effect of
      vitamin B status on the health of children with sickle cell disease-SS (SCD-SS)
      is not well described. The purpose of this study was to assess vitamin B(6)
      status of children with SCD-SS ages 3 to 20 years and determine its relationship
      to growth, dietary intake, and disease severity. PATIENTS AND METHODS: Vitamin
      B(6) status was assessed by serum pyridoxal 5-phosphate (PLP) concentration in
      subjects with SCD-SS and by urinary 4-pyridoxic acid (4-PA) concentration in
      other subjects with SCD-SS and healthy control children. Concentration of PLP was
      compared with anthropometric measures of growth and nutritional status, dietary
      intake, hematologic indices, and frequency of SCD-related illness. RESULTS: The
      PLP concentration of subjects with SCD-SS was 15.6 +/- 15.2 nmol/L. Seventy-seven
      percent had a PLP concentration below the deficiency criterion (20 nmol/L)
      suggested by the Dietary Reference Intakes (1998). Controlling for alkaline
      phosphatase, age, and gender, PLP concentration was associated positively with
      weight, body mass index, and arm circumference -scores and negatively with
      reticulocyte count. Urinary 4-PA was lower in children with SCD-SS versus
      controls, although 4-PA/creatinine values did not differ between groups.
      CONCLUSIONS: Children with SCD-SS had apparently low serum PLP concentrations in
      the absence of excess vitamin B(6) excretion, suggesting low vitamin B(6) status.
      Low serum PLP concentration was associated with indicators of poor nutritional
      status and may be related to increased hemolysis in children with SCD-SS.

PMID- 12218595
TI  - Streptococcus pneumoniae sepsis and meningitis during the penicillin prophylaxis
      era in children with sickle cell disease.
AB  - The purpose of this study was to determine the age-related risks, disease
      specific risks, and characteristics of serious pneumococcal infections in
      children with sickle cell disease (SCD) while penicillin prophylaxis was
      standard. The clinical experiences of three pediatric sickle cell programs
      spanning January 1, 1992, to May 31, 1998, were combined. Data were collected
      regarding the patients followed up and the characteristics of bacteremia and
      meningitis cases. Forty-seven pneumococcal infections (44 bacteremia, 3
      meningitis) among 40 patients with SCD were observed. Forty infections occurred
      in children with homozygous hemoglobin S (SS) during 4108 patient-years at a
      median age of 22 months; 7 occurred in double heterozygous hemoglobin SC (SC)
      children during 1777 patient-years at a median age of 23 months. Ten infections
      occurred among 9 SS children 5 years or older. Most children in whom infections
      developed were reportedly taking prophylactic penicillin and when older than 24
      months old had received Pneumovax (Merck & Co., Inc., West Point, PA, U.S.A. The
      following pneumococcal serotypes were identified in 15 cases studied: 6A, 6B, 9V,
      14, 15B, 18B, 18F, 19F, and 23F. Infections resulted in five deaths and two
      strokes. The observed severe pneumococcal infection rate in SS children younger
      than 5 years was less than that reported before penicillin prophylaxis,
      supporting routine penicillin prophylaxis in this specific population. The
      optimal duration of penicillin prophylaxis in older children with SCD remains
      unknown. The administration of 7-valent Prevnar (Wyeth Lederle Vaccines,
      Philadelphia, PA, U.S.A.) to children younger than 24 months old with SCD should
      be beneficial, based on the serotype data.

PMID- 12218596
TI  - Risk factors for microalbuminuria in children with sickle cell anemia.
AB  - PURPOSE: To determine the prevalence of microalbuminuria and to establish
      clinical characteristics associated with microalbuminuria in children with sickle
      cell anemia. PATIENTS AND METHODS: Urine samples of all children (homozygous SS)
      followed in the Medical College of Georgia's Children's Medical Center Sickle
      Cell Clinic were screened for microalbuminuria. Random samples were obtained from
      continent patients at routine office visits between September 1996 and November
      1999. A retrospective chart survey was performed to determine clinical correlates
      for microalbuminuria. Medical records were reviewed for age, sex, hemoglobin, and
      episodes of pneumonia, pain, aplasia, acute chest syndrome, priapism, and
      avascular necrosis. Demographic and clinical variables were compared with
      microalbuminuria by univariate and multivariate logistic regression. RESULTS: One
      hundred forty-two patients ages 21 months to 20 years made up the study group.
      The prevalence of microalbuminuria was 19%. Both increasing age and a lower
      hemoglobin level were found to correlate with microalbuminuria. By multivariate
      analysis, boys with microalbuminuria were likely to have a lower hemoglobin level
      and girls with microalbuminuria were likely to be older. None of the following
      factors were significantly related to microalbuminuria: pain, pneumonia, acute
      chest syndrome, priapism, avascular necrosis, or aplastic episodes. CONCLUSIONS:
      Microalbuminuria is strongly and directly related to age and strongly and
      inversely related to hemoglobin levels. Identification of risk factors for
      microalbuminuria may allow earlier intervention to prevent renal complications in
      patients with sickle cell disease.

PMID- 12218597
TI  - Complete response of recurrent cellular congenital mesoblastic nephroma to
      chemotherapy.
AB  - Congenital mesoblastic nephroma (CMN) is usually cured by surgery. The
      sensitivity of this tumor to chemotherapy is unknown. The recent description of a
      t(12;15)(p13;q25) chromosomal translocation in both cellular CMN and congenital
      infantile fibrosarcoma suggests that these entities have a common pathogenesis,
      and that cellular CMN might respond to chemotherapy like congenital infantile
      fibrosarcoma does. The authors describe three patients with recurrent cellular
      CMN who showed a complete response to chemotherapy. Based on these patients and a
      review of the literature, the authors suggest that chemotherapy be considered as
      a part of the therapy for recurrent or unresectable cellular CMN.

PMID- 12218598
TI  - Esthesioneuroblastoma in children.
AB  - Esthesioneuroblastoma (olfactory neuroblastoma) is a rare tumor of the olfactory
      epithelium. Approximately 1,000 cases have been described in the literature since
      the original description in 1924. It occurs in older individuals and is rare in
      children. The authors describe the clinicopathologic presentation in a series of
      five children treated with neoadjuvant/adjuvant chemotherapy and review the
      English literature for previously described patients younger than 18 years to
      assess clinical presentation, mode of treatment, and outcome in this age group.

PMID- 12218599
TI  - Treatment of pediatric ocular melanoma with high-dose interleukin-2 and
      thalidomide.
AB  - Uveal melanoma is the most common primary ocular malignancy, although it is rare
      in children, and patients presenting with metastatic disease have a median
      survival of only 2 to 5 months. The tumor is generally unresponsive to systemic
      chemotherapy, but immunotherapy may be effective in selected patients. This
      report describes an 8-year-old girl with metastatic uveal melanoma treated with
      high-dose, bolus interleukin-2 (IL-2) and the antiangiogenic agent thalidomide.
      She tolerated treatment well and initially responded with stable disease in the
      liver and pancreas for 23 months. New pulmonary metastases developed and she was
      re-treated with high-dose IL-2, resulting in regression of her liver lesions and
      stable pulmonary disease for more than 18 months. These results suggest that IL-2
      at high doses, and in combination with thalidomide, may be useful for uveal
      melanoma with tolerable side effects in children. Further study of this
      combination in children with immune-responsive tumors is warranted.

PMID- 12218600
TI  - Rhinocerebral mucormycosis in a boy with recurrent acute lymphoblastic leukemia:
      long-term survival with systemic antifungal treatment.
AB  - Rhinocerebral mucormycosis is rare in hematologic malignancies and usually leads
      to death within weeks. In contrast, chronic rhinocerebral mucormycosis takes a
      slowly progressive course and has not been reported in hematologic malignancies
      in children so far. The authors report the long-term survival of a boy with
      rhinocerebral mucormycosis in a relapse of acute lymphoblastic leukemia after
      allogeneic cord blood transplantation. The disease started acutely but took a
      chronic course thereafter. No surgical debridement was performed because of
      extensive involvement of the sinuses, orbits, and cerebrum. His long-term
      survival of 15 months is attributed to the long-range administration of liposomal
      amphotericin B, early neutrophil recovery, and slow progression of the relapsing
      acute lymphoblastic leukemia.

PMID- 12218601
TI  - CD3+CD4-CD8+NK- large granular lymphocytosis with neutropenia and evidence for
      clonality and T-cell receptor gene rearrangement: two pediatric cases.
AB  - The authors describe two pediatric cases of large granular lymphocytosis
      presenting early in the second decade of life with neutropenia and sepsis. They
      are among the youngest described in the literature. This report focuses on the
      advantages of detailed immunophenotypic and molecular analysis and highlights
      some of the controversies and uncertainties in the management of these patients,
      particularly the choice of immunosuppressive therapy. Immunosuppressive therapy
      in the two children described in this report resulted in improvement of
      neutropenia and clinical status, but this was not accompanied by the
      disappearance of the clonal population.

PMID- 12218602
TI  - Interpretation of fetal hemoglobin only on newborn screening for
      hemoglobinopathy.
AB  - Newborn screening for hemoglobinopathies rarely produces a fetal hemoglobin only
      result; it is most consistent with beta-thalassemia major, although other
      diagnoses are possible. The authors describe two unrelated African-American
      babies born in North Carolina whose newborn screening revealed fetal hemoglobin
      only. Both had a relatively benign clinical and hematologic picture. Molecular
      analyses indicated that both children are compound heterozygotes for beta
      thalassemia and pancellular (deletional) hereditary persistence of fetal
      hemoglobin, a rare and apparently benign condition. Accurate interpretation of
      the fetal hemoglobin only result on newborn screening requires thorough
      evaluation, including family studies and molecular analysis.

PMID- 12218603
TI  - Congenital dyserythropoietic anemia, type 1, in a polynesian patient: response to
      interferon alpha2b.
AB  - The authors attempted to assess the utility of interferon alpha2b treatment in a
      Polynesian girl with a relatively severe form of congenital dyserythropoietic
      anemia, type 1. The diagnosis was established using routine hematologic and
      biochemical tests, light and electron microscopy, and electrophoresis of red cell
      membrane proteins. Response to the treatment was monitored using the blood count
      and reticulocyte count. The patient was age 14 when interferon treatment was
      started. Previously, she had been partially dependent on transfusions, and
      gallstones and iron overload had developed. The dose of interferon alpha2b was
      initially 3 x 10 units three times a week for 1 year and 3 x 10 units twice a
      week thereafter. On this treatment, hemoglobin and reticulocytes increased and
      transfusions became unnecessary. In keeping with a few previous reports,
      interferon alpha2b proved to be effective in congenital dyserythropoietic anemia,
      type 1. The patient became transfusion-independent. More cases need to be studied
      to optimize the dosage of interferon alpha2b and determine how long the treatment
      can be tolerated.

PMID- 12218604
TI  - Infantile pyknocytosis: a forgotten or a dead diagnosis?

PMID- 12218605
TI  - Disseminated alveolar rhabdomyosarcoma in a child with spinal muscular atrophy.

PMID- 12218606
TI  - Inferior vena caval thrombosis with sickle cell disease and heterozygous protein
      s deficiency.

PMID- 12218607
TI  - Fellowship training in neurotology.

PMID- 12218608
TI  - Certificate of added qualifications.

PMID- 12218609
TI  - Scope of practice.

PMID- 12218610
TI  - Value of ear endoscopy in cholesteatoma surgery.
AB  - OBJECTIVE: The purpose of this study was to assess the value of ear endoscopy in
      cholesteatoma surgery and to demonstrate its consequence in improving surgical
      outcome. MATERIALS AND METHODS: A total of 92 ears with acquired cholesteatoma
      (primary or secondary) were operated on. In this prospective study, 82 cases were
      operated on by using canal wall up (CWU) technique, and 10 cases were on operated
      on by using canal wall down (CWD) procedure. Endoscopically guided ear surgery
      was incorporated complementary to the microscope as a principal part in the
      procedure. Second-look endoscopic exploration was performed on some selected
      cases, depending on the finding during the primary surgery and the postoperative
      findings of clinical and computed tomographic studies. RESULTS: In the primary
      surgery after completion of microscopic cleaning, the overall incidence of
      intraoperative residuals detected with the endoscope was 22.8%. Sinus tympani was
      the most common site of intraoperative residuals in both CWU and CWD groups,
      followed by the facial recess and the undersurface of the scutum in the CWU
      cases. Reconstruction of the hearing mechanism was performed in the primary
      surgery in 86 cases (93.5%) and postponed to the second stage in only six cases
      (6.5%). Out of the 82 CWU cases, 35 second-look endoscopic explorations (42.7%)
      were performed. Three recurrences (8.6%) were identified. Two cases showed a tiny
      residual cholesteatoma pearl, and the third showed a larger open residual
      cholesteatoma filling the sinus tympani and extending to the aditus. In this
      series, no morbidity or complication was encountered secondary to the use of
      endoscopes in the mastoid or middle ear. CONCLUSION: Incorporating the endoscope
      into the surgical armamentarium in otology contributes much to the concept of
      minimally invasive surgery. Minimally invasive endoscopic ear surgery should be
      accepted as a new horizon in ear surgery. In this study, it became obvious that
      despite the use of the endoscope in conjunction with the operating microscope,
      100% eradication of the disease still could not be achieved; however, the use of
      endoscopes did reduce the residual cholesteatoma rate.

PMID- 12218611
TI  - Neomalleus ossiculoplasty.
AB  - OBJECTIVE: To evaluate the role of ossiculoplasty techniques using neomalleus
      struts combined with assembly prostheses, in middle ear reconstruction. STUDY
      DESIGN: A retrospective case review of 272 consecutive ossiculoplasty cases in
      which the malleus was replaced with an autograft strut. BACKGROUND: Current
      ossiculoplasty methods have experienced tangible difficulties, including
      extrusion and displacement (columellae), plus inefficiency and instability
      (assemblies). SETTING: Private single-surgeon tertiary referral otologic
      practice. PATIENTS: Ossiculoplasty candidates in whom the malleus was unsuitable
      for assembly reconstructions because of disease or malpositioning. INTERVENTIONS:
      Ossicular reconstructions using an autograft strut to replace an absent or
      malpositioned malleus, combined with Spanner assembly prostheses. MAIN OUTCOMES
      MEASURES: Pure tone audiology, subdivided into Austin groups, and also
      progressive pathologic severity groups, using Surgical, Prosthetic, Infection,
      Tissues, Eustachian (SPITE) indicators. RESULTS: Two months postoperatively,
      neomalleus cases returned favorable results in comparison with those of previous
      techniques, in equivalent situations. The technique appeared to be durable in the
      longer term. CONCLUSIONS: Neomalleus techniques offer enhanced success rates when
      the malleus handle is displaced, diseased, or absent.

PMID- 12218612
TI  - Incudostapedial rebridging ossiculoplasty with bone cement.
AB  - OBJECTIVE: This study reports the authors' technique and hearing results with
      bone cement reconstruction of the incudostapedial chain. The technique is called
      incudostapedial rebridging ossiculoplasty. STUDY DESIGN: A retrospective analysis
      of the hearing results of the incudostapedial rebridging ossiculoplasty was
      performed on 15 patients. BACKGROUND: Recently, bone cements have been available
      commercially, and their use in otologic surgery is increasing. Polymaleinate
      glass ionomer cement is a commercially available bone cement that can be used to
      reconstruct a discontinuity between the incus and the stapes. SETTING: Tertiary
      referral center. PATIENTS: Disease-free or cleansed middle ear and mastoid and
      intact ossicular chain except for discontinuity between the long process of the
      incus and the head of the stapes. INTERVENTIONS: Therapeutic. MAIN OUTCOMES
      MEASURES: Functional results of incudostapedial rebridging ossiculoplasty.
      RESULTS: Of 15 patients, 9 achieved a successful hearing result (an air-bone gap
      within 20 dB) with incudostapedial rebridging ossiculoplasty after 1 year. The
      mean preoperative and postoperative air-bone gaps were 32.9 and 14.3 dB,
      respectively. CONCLUSIONS: Incudostapedial rebridging ossiculoplasty with bone
      cement is a cost-effective and safe procedure that yields good hearing results in
      selected patients.

PMID- 12218613
TI  - Expression of epidermal growth factor, tumor necrosis factor-alpha, and
      interleukin-1alpha in chronic otitis media with or without cholesteatoma.
AB  - OBJECTIVE: The object of this study was to compare the expression of epidermal
      growth factor, interleukin-1alpha, and tumor necrosis factor-alpha in chronic
      otitis media with or without cholesteatoma. BACKGROUND: It has been reported that
      cytokines and epidermal growth factor are effective in the bone resorption
      process in chronic otitis media. Bone resorption can also occur in chronic otitis
      media without cholesteatoma. However, comparative analysis is lacking. This issue
      has been investigated in a blind, controlled and prospective analysis. METHOD:
      The activities of interleukin-1alpha, tumor necrosis factor-alpha, and epidermal
      growth factor were determined by commercially available enzyme-linked
      immunosorbent assay kits in tissue biopsy samples from 16 patients without
      cholesteatoma and from 23 patients with cholesteatoma (cholesteatoma epithelium).
      To establish a control group, external auditory canal skin was randomly collected
      from two groups (21 patients). The Mann-Whitney and Kruskal-Wallis tests were
      used for statistical analysis. RESULTS: The levels of interleukin-1alpha, tumor
      necrosis factor-alpha, and epidermal growth factor in tissue samples from the
      group with cholesteatoma were significantly greater than those in the group
      without cholesteatoma and the control group. No correlation was observed with
      other clinical factors such as age, sex, and antibiotic coverage. CONCLUSION:
      Higher levels of cytokines in patients with cholesteatoma confirm that the
      destructive behavior of cholesteatoma is likely mediated by cytokines and
      epidermal growth factor and is the result of keratinocyte activity. Antibiotic
      treatment does not affect the level of cytokine concentration in patients with
      chronic otitis media and cholesteatoma, although the ear discharge subsides and
      inflammation-related symptoms regress in some cases.

PMID- 12218614
TI  - Hydroxyapatite prosthesis extrusion.
AB  - OBJECTIVE: To examine the mechanism of prosthesis extrusion and evaluate
      preoperative and postoperative variables associated with extrusion of
      hydroxyapatite prostheses for ossicular reconstruction. STUDY DESIGN:
      Retrospective case review. SETTING: Tertiary referral, university medical center.
      PATIENTS: Patients undergoing ossiculoplasty with a hydroxyapatite prosthesis and
      having at least six months follow-up. MAIN OUTCOME MEASURE: Prosthesis extrusion,
      defined as loss of the tympanic membrane resulting in exposure of the prosthesis.
      Extrusion is further classified into early (< 2 months) and late (> 6 months).
      RESULTS: Early extrusion or tympanoplasty graft failure occurred in 15/195 cases
      (8%). Late extrusion was seen in 17/125 cases (14%). Cases exhibiting late
      extrusion had a significantly greater incidence of postoperative atelectasis (p <
      0.0001), recurrent otitis media (p < 0.0001), and myringitis (p = 0.003) than
      those with retention of the prosthesis. Regression analysis found an abnormal
      contralateral ear increased the risk of postoperative recurrent otitis media,
      while staged surgery reduced the risk, odds ratios of 3.56 (95% confidence
      interval 2.20-9.37) and 6.84 (95% CI 4.24-17.76) respectively. There were no
      preoperative variables that predicted postoperative atelectasis or myringitis.
      CONCLUSIONS: Recurrent otitis media, myringitis, and atelectasis developing after
      ossiculoplasty are associated with a greater risk of prosthesis extrusion.
      Predicting postoperative complications from preoperative and intraoperative
      findings proved difficult. Measures to prevent atelectasis, such as covering the
      prosthesis with cartilage, are recommended at the time of ossiculoplasty.

PMID- 12218615
TI  - Bioactive glass ceramic particles as an alternative for mastoid obliteration:
      results in an animal model.
AB  - HYPOTHESIS: This study was conducted to evaluate the use of the bioactive glass
      ceramic particulate NovaBone Bioglass as a graft material for mastoid cavity
      obliteration in an animal model. BACKGROUND: Canal wall down procedures in
      otologic surgery may result in a problematic mastoid cavity. Mastoid cavity
      obliteration can potentially prevent or correct this problem. Many techniques and
      implant materials have been used for mastoid obliteration, but no single graft
      material has proved to be ideal. METHODS: Mongolian gerbils received tympanic
      bulla obliteration using the NovaBone Bioglass particulate. Nine weeks after
      implantation, the animals were killed, and histologic sections were prepared.
      Histologic evaluation was performed to evaluate new bone formation within the
      implant. RESULTS: Wound healing occurred without complication. Mature trabecular
      bone was observed throughout the entire thickness of the implant material.
      Extensive neovascularity was observed within the graft material. There was no
      histologic evidence of inflammatory reaction or short-term resorption.
      CONCLUSIONS: The extensive new bone formation obtained with bioactive glass
      ceramic particles in this study makes this material a potential alternative
      resource as a graft material for mastoid obliteration.

PMID- 12218616
TI  - Dextran-induced pulmonary edema in patients with sudden deafness.
AB  - OBJECTIVE: Pulmonary complication in cases of sudden deafness after dextran
      treatment is rarely reported. This study discusses the management of two cases
      and reviews the current literature. PATIENTS: Two (1%) of 204 patients with
      sudden deafness patients had fever, cough, and dyspnea after intravenous dextran
      infusion. Pulmonary edema was diagnosed after chest radiographic examination.
      RESULTS: After interruption of dextran, subsequent supportive treatment relieved
      chest discomfort and fever without any sequelae. The results of chest radiograph
      and laboratory studies, including hemogram, renal function, and arterial blood
      oxygen saturation, were normal. CONCLUSIONS: Patients receiving dextran treatment
      should have their clinical symptoms, renal function, chest radiographs, hemogram,
      and coagulation profiles monitored. If fever, bleeding, cough, or dyspnea occurs
      during treatment, dextran must be immediately stopped. Subsequent treatment
      should focus on dextran clearance to prevent further cascade complications.

PMID- 12218617
TI  - Effect of prostaglandin E1 on idiopathic sudden sensorineural hearing loss: a
      double-blinded clinical study.
AB  - OBJECTIVE AND STUDY DESIGN: The authors conducted a prospective, randomized,
      double-blinded clinical trial for the purpose of elucidating the effects of
      prostaglandin E1 (PGE1) on idiopathic sudden sensorineural hearing loss. SETTING
      AND PATIENTS: With the approval of the institute ethics committee, a total of 57
      consecutive patients with diagnoses of idiopathic sudden sensorineural hearing
      loss were included in the study. The patients in the PGE1 group received
      continuous infusion containing 60 microg PGE1 and 100 mg hydrocortisone for 7
      days, and the patients in the placebo group were treated with continuous infusion
      containing an inactive placebo and 100 mg hydrocortisone. RESULTS: No significant
      differences were observed in the improvements of pure-tone average and subjective
      symptoms between the PGE1 and the placebo groups. However, the hearing
      improvement at high frequencies (4 kHz and 8 kHz) was significantly higher in the
      PGE1 group than in the placebo group, especially in the patients with severe
      tinnitus. CONCLUSIONS: These results failed to prove a beneficial effect of PGE1
      in the treatment of idiopathic sudden sensorineural hearing loss. Further studies
      will be needed to clarify the pharmacologic actions of PGE1 in the cochlea.

PMID- 12218618
TI  - Comparison of different vibrant soundbridge audioprocessors with conventional
      hearing AIDS.
AB  - OBJECTIVE: To compare the functional gain of different Symphonix Soundbridge
      audioprocessors (HF-processor and D-processor) to preoperatively fitted
      conventional hearing aids of patients with mild to severe sensorineural hearing
      loss in the high-frequency range. STUDY DESIGN: In a prospective study, the
      Symphonix Soundbridge (HF-processor and D-processor) fitting results were
      evaluated and compared with conventional hearing aids. Postoperative air and bone
      conductances, the functional gain of warble-tone measurements, speech
      audiometric, and subjective outcome testing (Abbreviated Profile of Hearing Aid
      Benefit questionnaire) were studied. SETTING: Tertiary referral center. PATIENTS:
      Five patients (ages, 54-69 yr) with mild to severe sensorineural deafness in the
      high-frequency range, but no progression of hearing loss during the last two
      years, were initially fitted with the so-called HF-processor, then subsequently
      fitted with the D-processor, which was a fully digital one. RESULTS: One year
      after implantation of the Symphonix Soundbridge device, unchanged, stable air and
      bone conductances were found (except for one minor change). Over the whole
      frequency range (0.5-8.0 kHz), a mean gain of 16.1 dB (HF-processor), 27.1 dB (D
      processor), and 15.2 dB (hearing aid) was found. The Symphonix Soundbridge device
      with different audioprocessors led to improved hearing in speech audiometric
      testing. The data show a significant improvement of hearing compared with
      conventional hearing aids in quiet, and a better functional gain in noise for the
      Symphonix Soundbridge system. The Abbreviated Profile of Hearing Aid Benefit
      questionnaire also revealed that the implant resulted in significant differences
      compared with conventional hearing aids in almost all subcategories. CONCLUSION:
      The Symphonix Soundbridge device can improve the hearing benefit of moderately to
      severely hearing handicapped patients-particularly in those with a high-frequency
      hearing loss-when compared with the conventional hearing aids of these patients,
      as evidenced by objective and subjective measurements. The Symphonix Soundbridge
      D-processor showed further improvements and resulted in an additional hearing
      benefit that was superior to that of the previously fitted HF-audioprocessor.
      This is owing to the refinements and upgrades in audioprocessor technology.

PMID- 12218619
TI  - Cost-benefit analysis of pediatric cochlear implantation: German experience.
AB  - HYPOTHESIS: To explore, from the payers' perspective, the cost-benefit ratio of
      pediatric cochlear implantation for congenitally deaf and prelingually deafened
      children compared with children with hearing aids. The study should verify the
      hypothesis that educational and associated costs increase with age at
      implantation and that these can be below costs for children with hearing aids.
      METHODS: Children who received implants at the Medical University of Hanover at
      different ages (Group 1, 0-1.9 yr; Group 2, 2-3.9 yr; Group 3, 4-6.9 yr) were
      compared with deaf children using hearing aids (Group 4). Sick funds were the
      payers for direct and indirect costs, and public authorities were the payers for
      educational costs. Educational settings were used to measure for benefits. All
      costs related to the hearing deficiency were included up to the age of 16 years
      on the basis of 1999 currency values. A scenario analysis was used to explore the
      impact of variation of costs and discount rates. RESULTS: Total costs for the
      three age groups of children with implants were from euro 138,000 (approximately
      US$113,100) to euro 177,000 (approximately US$152,700), compared with euro
      160,000 (approximately US$138,000) for hearing aid users. CONCLUSION: This study
      supports the view that pediatric cochlear implantation provides positive cost
      benefit ratios compared with hearing aid users, depending on the age at
      implantation. Implantation is strongly recommended from the payers' perspective
      for children implanted before the age of 2 years.

PMID- 12218620
TI  - Hearing restoration with auditory brainstem implant in three children with
      cochlear nerve aplasia.
AB  - OBJECTIVE: To verify the possibility of auditory habilitation in children with
      aplasia and hypoplasia of the cochlear nerve by direct electrical stimulation of
      the cochlear nuclei with an auditory brainstem implant. STUDY DESIGN:
      Retrospective case review. SETTING: Study conducted at the Ear, Nose, and Throat
      Department of the University of Verona, Italy. PATIENTS: Three children, aged 4,
      3, and 2 years, respectively, with severe bilateral cochlear malformations and
      cochlear nerve aplasia have received an auditory brainstem implant at this
      institution in the past 2 years. INTERVENTION: The classic retrosigmoid approach
      was used. Correct positioning of the electrodes was evaluated using electric
      auditory brainstem responses and neural response telemetry. Before the patients
      were discharged, high-resolution computed tomography with a bone algorithm
      reconstruction technique was performed to evaluate electrode placement. The
      auditory brainstem implant was activated 30 to 60 days after implantation.
      RESULTS: No postoperative complications were observed. To date, 21, 18, and 8
      electrodes, respectively, have been activated in the three children. The first
      patient, 12 months after activation, had achieved good environmental sound
      awareness, good speech detection, and some speech recognition. The second child,
      8 months after activation, had achieved good environmental sound awareness and
      moderate speech detection. The third patient, 1 month after activation, had
      obtained good environmental sound awareness. CONCLUSION: This study indicates
      that auditory brainstem implantation is technically feasible in children with
      cochlear nerve aplasia. The early results suggest the possibility of achieving
      auditory habilitation with auditory brainstem implantation in this population.

PMID- 12218621
TI  - Auditory brainstem implant part II: subjective assessment of functional outcome.
AB  - OBJECTIVE The purpose of this study was to present the patients' recommendations
      and judgments about their hearing and communication abilities with the help of
      the auditory brainstem implant. STUDY DESIGN: Prospective study. SETTING:
      Tertiary referral center. PATIENTS AND METHODS: This evaluation was based on the
      data obtained by the self-administered questionnaires designed for the European
      Auditory Brainstem Implant Multicenter Clinical Trial. Eleven patients who had
      used their auditory brainstem implant for a minimum of 6 months to a maximum of
      41 months were evaluated with the help of these questionnaires. RESULTS: All the
      patients had used their implant on a regular daily basis for an average of 13
      hours per day. None of them experienced any side effects during the daily use of
      the device. Nine patients (82%) used their auditory brainstem implant in both
      quiet and noisy surroundings. The most common cause of disturbance was a noisy
      surrounding. All the patients were able to distinguish speech from environmental
      sounds. The role of the auditory brainstem implant in differentiating various
      environmental sounds was considered to be very useful by 9 patients (82%). As an
      adjuvant to lip-reading, the auditory brainstem implant was considered most
      useful for understanding speech in quiet surroundings. DISCUSSION AND CONCLUSION:
      It was concluded that the auditory brainstem implant is an effective support for
      receiving and, to some degree, differentiating environmental sounds, and that as
      an adjuvant to lip-reading, it enhances speech perception, especially in quiet
      surroundings. A comparison between the results of this study and the results of
      the audiologic tests presented in Part I of this study (published earlier)
      revealed that patient satisfaction was not directly correlated with the results
      of the objective auditory tests. In general, patients' judgments of their
      individual hearing and communication abilities usually rated higher than could
      have been predicted by the objective audiometric data.

PMID- 12218622
TI  - Cochlear implantation for adolescents and adults with prelinguistic deafness.
AB  - OBJECTIVE: Previous studies have suggested that individuals with long-term
      prelinguistic deafness who receive cochlear implants show little improvement in
      speech recognition skills. The purpose of this study was to examine the auditory
      functioning of individuals with prelinguistic deafness who received cochlear
      implants after the age of 12. STUDY DESIGN AND SETTING: A retrospective study of
      open-set speech recognition was undertaken for 15 patients (adolescents and
      adults) with prelinguistic deafness who underwent implantation in the Ottawa
      Cochlear Implant Program. The results of open-set speech perception tests, both
      words and sentences, were reviewed to assess auditory functioning after
      implantation. Qualitative data using the Performance Inventory for Profound and
      Severe Loss questionnaire were also collected for the adults. RESULTS AND
      DISCUSSION: The results of this study indicate that individuals with long-term
      prelinguistic deafness can achieve significant open-set speech understanding with
      a cochlear implant, although there is a wide range of performance across
      patients. The results ranged from 0% to 74% for words and 0% to 98% for
      sentences.

PMID- 12218623
TI  - The binaural digisonic cochlear implant: surgical technique.
AB  - The surgical technique of cochlear implantation is currently well established. It
      is sure and efficient. The results of the cochlear implant concerning speech
      perception are good and have a favorable cost/efficiency ratio. However, some
      points remain to be researched. Bilateral implantation allows one to obtain a
      binaural perception and especially to increase, theoretically, the possibilities
      of frequency discrimination by reducing interactions between electrodes and
      therefore improving the patient's performance. Nevertheless, it seems important
      to caution against placing two implants in one patient, especially for economic
      reasons. Thus, we have developed, with the MXM Company, a concept of a unique
      implant able to stimulate both cochleas with a single processor and a single
      receiver: the Binaural Digisonic cochlear implant. This article describes the
      Binaural Digisonic system, the surgical technique as developed by postmortem
      dissection, and the first two implantations in patients.

PMID- 12218624
TI  - Speech reception thresholds obtained in a symmetrical four-loudspeaker
      arrangement from bilateral users of MED-EL cochlear implants.
AB  - OBJECTIVE: The purpose of the study was to investigate speech reception in noise
      in subjects who had undergone bilateral implantation with multichannel cochlear
      implants. METHODS: Nine adults with bilateral MED-EL implants were included in
      the study. The subjects were tested using both implants and the better implant
      only. Tests were performed in a symmetrical setup, which ideally eliminates any
      head shadow effect. Speech tests included sentences in quiet and at various
      signal-to-noise ratios. From the results, the gain in signal-to-noise ratios at
      the speech reception threshold was determined. RESULTS: All subjects showed a
      substantial gain in signal-to-noise ratios of approximately 4 dB on average. In
      addition, the gain in signal-to-noise ratios was essentially stable for as long
      as 4.4 years. CONCLUSIONS: The results indicate that bilateral cochlear implant
      users are able to binaurally process speech.

PMID- 12218625
TI  - Multislice computed tomographic imaging in temporal bone dysplasia.
AB  - OBJECTIVES: To evaluate the impact of multislice computed tomographic (MSCT)
      imaging, a recently developed computed tomographic technique, on imaging of
      temporal bone malformations. STUDY DESIGN: Retrospective case review. SETTING:
      The study was performed at a tertiary referral center. PATIENTS: High-resolution
      temporal bone studies of 168 consecutive patients were reviewed for various
      temporal bone malformations. MAIN OUTCOME MEASURES: Visualization of various
      dysplastic conditions of the temporal bone without the need for supplementary
      scan procedures or additional imaging techniques. INTERVENTION: MSCT imaging was
      performed on a scanner with four detector rows by using the following parameters:
      120 kV, 50 mA/s, 0.5-mm slice thickness, 0.2-mm reconstruction increment, pitch
      factor of 0.75, and a field of view of 160 mm. Two-dimensional and three
      dimensional image reconstructions were performed subsequent to data transfer to a
      workstation. In one patient suspected of having a vascular dysplasia, high
      resolution MSCT imaging was supplemented by multislice computed tomographic
      angiography. RESULTS Temporal bone dysplasias were encountered in 28 patients
      (16.7%), affecting the external auditory canal (n = 15), the middle ear (n = 18),
      the inner ear (n = 5), and the vascular system (n = 3). All temporal bone
      dysplasias were visualized by two-dimensional and three-dimensional images of
      excellent detail resolution. In none of the patients were supplementary computed
      tomographic scans necessary, except for one patient with evidence of an aberrant
      course of the internal carotid artery. Multislice computed tomographic
      angiography obviated the need for invasive diagnostic procedures. CONCLUSION:
      MSCT imaging of the temporal bone allows for comprehensively assessing various
      dysplasias through high-quality two-dimensional and three-dimensional image
      reconstructions.

PMID- 12218626
TI  - Cerebellar arteriovenous malformation with facial paralysis, hearing loss, and
      tinnitus: a case report.
AB  - OBJECTIVE: To describe cerebellar arteriovenous malformation in a 21-year-old man
      with symptoms resembling those of ear disease and to discuss the relationship
      between the findings of neurotologic examination and magnetic resonance imaging.
      STUDY DESIGN: Case report. SETTING: Department of Otolaryngology, Head-and-Neck
      Surgery of the Kyoto University Hospital, which is a tertiary care center, in
      Kyoto, Japan. PATIENT: A 21-year-old man had cerebellar arteriovenous
      malformation and symptoms resembling those of ear disease: recurrent left facial
      paralysis, left retrocochlear hearing loss, and tinnitus. Auditory brainstem
      responses showed only waves I and II on his left side. Downbeat nystagmus was
      seen by anteflexion and retroflexion of his neck. He also experienced a slight
      sensory disturbance on the left side of his face and right lower extremity.
      Magnetic resonance imaging and vertebral angiography revealed a cerebellar
      arteriovenous malformation and a varix functioning as a drainer of the
      arteriovenous malformation surrounded by an edematous region probably induced by
      a small hemorrhage in the brainstem. INTERVENTION: Conservative treatment,
      including intravenous prednisolone, vitamin B12, and oral adenosine triphosphate
      was performed followed by total extirpation of the arteriovenous malformation.
      CONCLUSION: In examining patients with peripheral facial paralysis (sometimes
      recurrent with a short interval) and other symptoms resembling those of ear
      disease, especially those suggesting certain central disorders, it is important
      to take intracranial arteriovenous malformation into consideration because the
      condition may be sometimes life threatening if overlooked.

PMID- 12218627
TI  - The Chiari I malformation and the neurotologist.
AB  - OBJECTIVE: The first objective of this paper is to report the clinical symptoms
      of 77 patients and the results of their neurologic, vestibular, and audiological
      evaluations done with magnetic resonance imaging, which confirmed Chiari I
      malformations. The second objective is to report how the results of a vestibular
      evaluation can help neurosurgeons decide on the need for surgical treatment.
      STUDY DESIGN: Retrospective chart review of 77 patients seen between 1988 and
      2000. SETTING: Tertiary care center. PATIENTS: The clinical data of patients
      under diagnoses of Chiari I malformation, which was filed in the vestibular
      laboratory computer, was analyzed. INTERVENTION: The cases included in this study
      were derived from a population of patients who were evaluated for dizziness,
      hearing loss, and tinnitus in the Torok Vestibular Laboratory. MAIN OUTCOME
      MEASURE: Occurrence of central vestibular findings in the patients with Chiari I
      malformation. RESULTS: In this group of 77 patients, 10 had bilateral
      sensorineural hearing loss and 22 had unilateral sensorineural hearing loss of
      varying severities. Horizontal spontaneous nystagmus was noted in 27 patients,
      vertical upbeat nystagmus in 3, and downbeat nystagmus in 4 others. Saccadic
      dysmetria was noted in 4 patients, optokinetic nystagmus was impaired in 3, and
      smooth-pursuit impairment was noted in 12 of the group. Positional nystagmus was
      noted in 9 patients. The Torok monothermal caloric test showed normal responses
      in 19 patients, hyperactive responses in 43, decruitment in 45, and rebound
      caloric nystagmus in 20. Surgical decompression of the Chiari I malformation was
      completed in 33 patients. CONCLUSION: From this study it is clear that the
      results of the basic vestibular function-test battery reflect the functional
      deficit in the vestibulocerebellum that is presumed by its ectopic position.
      These tests results have given our neurosurgeons a stronger foundation on which
      to base surgical decisions for this disease.

PMID- 12218628
TI  - cDNA microarray analysis of vestibular schwannomas.
AB  - BACKGROUND: Vestibular schwannomas are known to harbor mutations in the
      neurofibromatosis type 2 tumor suppressor gene, but the mechanism of the
      neurofibromatosis type 2 tumor suppressor gene action is not well understood.
      Identification of genes differentially expressed in normal and diseased tissues
      through the use of a large-scale, cDNA microarray approach may lead to increased
      understanding of pathways that lead to tumor formation. OBJECTIVE: The objectives
      of this study were to evaluate the gene expression profiles in vestibular
      schwannomas in comparison with normal vestibular nerve tissues and to identify
      pathways that may be altered in schwannomas. METHODS: Total RNA was extracted
      from one normal vestibular nerve and seven vestibular schwannomas. The normal
      vestibular nerve was from one of the seven patients with small vestibular
      schwannomas. Radiolabeled cDNA was synthesized and hybridized to cDNA microarray
      filters that contained 25,920 known genes or expressed sequence tags. Expression
      profiles were imaged and analyzed. Selected genes that showed three-fold or
      greater difference in the intensity between the normal nerve and the schwannomas
      were further examined by real-time polymerase chain reaction and by
      immunohistochemical staining. RESULTS: Forty-two genes (0.2%) were upregulated 3
      fold or more in at least 5 of the 7 tumors when the filter images were compared
      with a normal adjacent vestibular nerve. Among them, osteonectin, an angiogenesis
      mediator, and RhoB GTPase, which is important in cell signaling, were
      significantly upregulated in 5 of 7 tumors. Among genes that were downregulated,
      an apoptosis-related LUCA-15 gene was highly underexpressed in 6 of 7 schwannomas
      when compared with the normal nerve. Also, ezrin, a relative of the NF2 protein,
      was significantly downregulated in 5 of 7 tumors. Real-time PCR and
      immunohistochemistry data support the cDNA microarray findings. CONCLUSION: Our
      cDNA microarray analysis of schwannomas suggested several interesting and
      potentially important tumorigenesis pathways associated with vestibular
      schwannoma formation. Further in vivo study is necessary to define the roles of
      these identified genes and their potential relationships with the
      neurofibromatosis type 2 tumor suppressor gene.

PMID- 12218629
TI  - Vestibular function after acoustic neuroma removal with preservation of one
      branch of the vestibular nerve.
AB  - BACKGROUND: Vestibular compensation after acoustic neuroma surgery is affected by
      many parameters. Apart from surgical approach, age of the patient, and
      comorbidity, the use of rehabilitative vestibular training and the degree of
      preoperative vestibular compensation play their respective roles. OBJECTIVE: To
      examine whether and how surgical preservation of one branch of the vestibular
      nerve affects the compensation process in patients after acoustic neuroma
      removal. STUDY DESIGN: Prospective study involving 29 patients with acoustic
      neuromas. In 15 patients operated on by the middle fossa or retrosigmoid
      approach, one branch of the vestibular nerve could be preserved intraoperatively,
      and the course of the compensation process was followed (Group 1). Fourteen other
      patients with acoustic neuroma, who were operated on via a translabyrinthine
      approach, served as a control group (Group 2). MAIN OUTCOME MEASURE: The
      evaluation of vestibular compensation was accomplished clinically, by
      electronystagmography, and by dynamic posturography. RESULTS: An accelerated
      vestibular compensation was found in all examinations for Group 1, and 3 months
      after surgery 47% of the patients in this group were back to work without
      substantial restrictions, compared with 29% of Group 2. At the end of 6 months,
      however, there was no more significant difference between the two groups.
      CONCLUSION: The long-term results of vestibular compensation do not seem to be
      influenced by partial preservation of the vestibular nerve, whereas the
      compensation process seems to be accelerated when the nerve is partially
      preserved.

PMID- 12218630
TI  - Clinical report on the L95P mutation in a Dutch family with paraganglioma.
AB  - OBJECTIVE: To describe the new L95P mutation of the paraganglioma 1 gene for
      glomus tumors in a Dutch paraganglioma 1 family with six affected family members
      and to report the clinical findings and results of treatment in nine glomus
      tumors with a maximum follow-up of 34 years. SETTING: Tertiary referral centers.
      RESULTS: Mutation analysis of the SDHD gene of paraganglioma 1 showed the L95P
      mutation in six affected family members and two nonaffected carriers protected
      from becoming affected by genomic imprinting. In six affected family members,
      nine glomus tumors (five glomus caroticum tumors, two glomus vagale tumors, and
      two glomus jugulare tumors) were traced. The ages at presentation varied from 25
      to 61 years. In two of six affected family members with a total of four tumors,
      all the tumors were traced in the extended family study, using magnetic resonance
      imaging; at that time these tumors were silent. After radiotherapy in one patient
      at the age of 34 years, a T4 planocellular carcinoma of the tongue occurred
      within the previous radiation field 27 years later, when the patient was 61 years
      old. Volume measurements of three untreated glomus tumors (two glomus vagale
      tumors, one glomus caroticum tumor) during 25 months showed an increase in two
      tumors (left glomus caroticum, left glomus vagale tumor) and a decrease in one
      tumor (right glomus vagale tumor). Surgery to remove two bilateral and one
      unilateral glomus caroticum tumors was successful. A wait-and-see policy is being
      applied to two glomus vagale tumors. CONCLUSIONS: In family members of
      paraganglioma 1 patients, mutation analysis can be used to make an early
      diagnosis of glomus tumors. Radiotherapy may have induced a carcinoma. Modalities
      of treatment can include a wait-and-see policy. Long-term follow-up studies on
      the natural course of glomus tumors are needed to improve decisions about
      treatment modalities.

PMID- 12218631
TI  - Temporal bone hemangiomas involving the facial nerve.
AB  - OBJECTIVE: Hemangiomas of the facial nerve are rare tumors that can mimic more
      common temporal bone tumors such as vestibular schwannomas and facial nerve
      schwannomas. This article reviews the diagnostic challenges in the surgical
      treatment of facial nerve hemangiomas. STUDY DESIGN: Two case reports and
      literature review. RESULTS: Early diagnosis and surgical excision of facial nerve
      hemangiomas can sometimes allow tumor removal with facial nerve preservation. In
      patients in whom the facial nerve needs to be resected to remove the hemangioma,
      primary anastomosis or cable nerve grafting can yield House-Brackmann Grade
      III/VI postoperative facial nerve function. CONCLUSION: Complete surgical
      excision of facial nerve hemangiomas with primary facial nerve repair (when
      necessary) is the treatment of choice for these lesions.

PMID- 12218632
TI  - Facial nerve grading systems (1985-2002): beyond the House-Brackmann scale.
AB  - OBJECTIVE To assess methods of evaluating the function of the facial nerve that
      have been introduced over the past 15 years, particularly in comparison with the
      House-Brackmann scale. DATA SOURCES A Medline search was undertaken of the
      English-language medical literature between 1983 and 2000 to identify proposed
      methods of evaluating facial nerve function. STUDY SELECTION Although all grading
      systems were considered, attention was focused on the systems that provided
      improvements in either precision or ease of use. CONCLUSIONS Because of the
      limitations and subjectivity of the House-Brackmann scale, several new scales of
      various degrees of objectivity and ease of use have been introduced. The
      Nottingham system offers a more objective but easy-to-use facial nerve grading
      system that has been demonstrated to be valid and that would be easy for the
      average practitioner to adopt. The authors propose a more systematic evaluation
      of this system to determine whether its widespread application is appropriate.

PMID- 12218633
TI  - Immunologic abnormalities and surgical experiences in recurrent facial nerve
      paralysis.
AB  - OBJECTIVE: To document immunologic findings in patients with recurrent facial
      paralysis (RFP) and to compare the results of the surgery with the results of
      medical treatment. STUDY DESIGN: Retrospective case review. SETTING: Tertiary
      care referral center. PATIENTS: Nine patients with RFP were reviewed.
      INTERVENTION: Patients underwent nonspecific antibody detection, protein
      electrophoresis (in blood and cerebrospinal fluid [CSF]) and oligoclonal band
      determination for immunoglobulin G, A, and M (in CSF). The extended subtotal
      facial nerve decompression via the transmastoid and transattic route was
      performed in four patients. Five patients received medical treatment only
      (steroids, vitamin B). RESULTS: Two patients had the complete and four patients
      had the oligosymptomatic form of Melkersson-Rosenthal syndrome. The other three
      patients were diagnosed with idiopathic RFP. Serum immunoglobulin G was high in
      seven of nine patients (77%). CSF protein electrophoresis demonstrated an
      elevated albumin fraction in six of nine patients (66%). CSF immunoglobulin G was
      high in four of nine patients (44%). The oligoclonal band in CSF was negative in
      all patients. Mean follow-up time was 5.2 +/- 2.6 years and 3 +/- 1.5 years for
      surgically treated patients and medically treated patients, respectively. None of
      the patients who underwent the surgery demonstrated recurrence. Although marked
      recovery was observed in patients who had received medical treatment, three of
      them had recurrence during the follow-up period. CONCLUSION: Serologic test
      results have demonstrated immune system involvement in cases of idiopathic RFP
      and in cases of Melkersson-Rosenthal syndrome, providing no distinction between
      the two. There was no sign substantiating local antibody production in CSF, which
      implies that the elevated antibodies in CSF were peripheral in origin. Although
      the serologic test results were not conclusive for a specific diagnosis, they
      support an immune-mediated pathogenesis. Despite the small number of patients who
      underwent the extended transmastoid facial nerve decompression, our follow-up
      data were suggestive for the prevention of recurrences.

PMID- 12218634
TI  - Secretion and dynamics of herpes simplex virus in tears and saliva of patients
      with Bell's palsy.
AB  - OBJECTIVE: For clarification of the direct relationship between the reactivation
      of herpes simplex virus and the development of Bell's Palsy, a detection of the
      virus genome by deoxyribonucleic acid diagnostics and a quantitative analysis of
      its time-course change are both needed. The authors detected the HSV genome in
      specimens from patients with Bell's Palsy, quantified its number of copies, and
      examined time-course changes. SUBJECTS AND METHODS: The subjects were 16 patients
      with Bell's Palsy. The tear fluid and saliva from the submandibular gland and the
      parotid gland were separately collected from the affected and unaffected sides
      twice or more. A total of 244 specimens were subjected to extraction of
      deoxyribonucleic acid, polymerase chain reaction, and microplate hybridization.
      RESULTS: Herpes simplex virus-1 deoxyribonucleic acid was detected in 38
      specimens (11.8%) from 5 patients (31%). The high detection (28.5%) was obtained
      within 2 weeks after onset. Detection at 3 weeks and later (2.8%) was
      significantly lower ( < 0.05). In three cases, deoxyribonucleic acid was also
      found on the unaffected side in the initial phase of the disease, but detection
      on that side (18.9%) was significantly lower than on the affected side (83.8%) (
      < 0.01). The number of copies of the herpes simplex virus-1 genome was large on
      the affected side and early after the onset of the disease. CONCLUSIONS: The
      reactivation of herpes simplex virus-1 on the affected side is involved as a
      pathogenic factor of Bell's Palsy. A reactivation of herpes simplex virus-1 may
      be generated even on the unaffected side in the early phase of the disease.
      Herpes simplex virus deoxyribonucleic acid was not detected in any of the
      examined specimens collected from the remaining 11 cases. The need for constant
      study to clarify other causative factors of Bell's Palsy remains.

PMID- 12218635
TI  - Contralateral sound stimulation suppresses the compound action potential from the
      auditory nerve in humans.
AB  - BACKGROUND: In the past decade, contralateral sound suppression of otoacoustic
      emissions has been extensively used to study the role of the medial olivocochlear
      efferent in humans. In most studies, the suppressive effect of contralateral
      sound stimulation was not greater than 2 to 4 dB. However, the relation between
      the degree of otoacoustic emission reduction and the neural auditory threshold is
      unknown. METHODS: The current study investigates the effect of contralateral
      sound stimulation by measuring compound action potential response from the
      auditory nerve during retrosigmoid surgery in humans. RESULTS: Although only a
      small number of subjects responded to contralateral sound stimulation, we report
      that efferent activation by contralateral sound stimulation results in 10 dB
      effective neural attenuation. CONCLUSIONS: Together with previous otoacoustic
      emission measurements in humans, this result demonstrates that the suppressive
      effect of contralateral noise suppression is greater when measured with compound
      action potential than otoacoustic emissions, and that contralateral sound
      suppressive effect is at least as strong in humans as in animals.

PMID- 12218636
TI  - Deoxyribonucleic acid contamination in archival human temporal bones: a
      potentially significant problem.
AB  - HYPOTHESIS: Contamination of archival human temporal bones with extraneous
      deoxyribonucleic acid may represent a potentially significant problem in the
      analysis of nucleic acids isolated from archival specimens. BACKGROUND: During
      the past decade, there has been growing interest in the development of molecular
      biologic techniques that can be applied to the investigation of pathologic
      changes in archival human temporal bones. The impetus for the development of
      these techniques is in part related to the fact that the temporal bone
      collections represent a repository of archival material compiled over decades,
      which is not available from living patients. METHODS: An archival human temporal
      bone specimen from a male patient with the Mohr-Tranebjaerg syndrome (formerly
      called DFN-1) and a well-characterized mutation was analyzed for the presence of
      the mutation by a standard method for extraction, isolation, amplification, and
      sequencing of deoxyribonucleic acid. The experiment was repeated four times.
      RESULTS: The deoxyribonucleic acid sequence from three of four extractions was
      normal. The known mutation was easily and repeatedly demonstrated in a blood
      sample from the same individual. Because Mohr-Tranebjaerg syndrome is X-linked,
      there is only one allele, and therefore there is no potential endogenous source
      to account for the normal sequence that was amplified. Contamination of the
      tissue sections by extraneous deoxyribonucleic acid presumably occurred during
      acquisition and processing of the temporal bone. CONCLUSIONS: Contamination of
      archival temporal bones with exogenous deoxyribonucleic acid is a significant
      potential problem that must be considered in the interpretation of the results of
      deoxyribonucleic acid retrieved from archival sections. The authors recommend
      collecting blood samples from temporal bone donors in the future to ensure the
      availability of a reliable source of deoxyribonucleic acid.

PMID- 12218637
TI  - Telomerase activity, telomere length, and apoptosis: a comparison between
      acquired cholesteatoma and squamous cell carcinoma.
AB  - BACKGROUND: Cholesteatoma disease is characterized by accumulation of
      keratinizing epithelium. Several molecular markers of tumor formation have been
      found in cholesteatoma (e.g. upregulation of matrix metalloproteinases, c and
      activation of angiogenesis). Other molecular findings clearly distinguish between
      cholesteatoma and malignant tumors (e.g., lack of chromosomal instability, intact
      checkpoint responses). To further distinguish the molecular mechanisms in
      cholesteatoma from malignant tumors, the authors determined telomerase activity
      and telomere length in both tissue types. METHODS: To evaluate the role of
      telomerase activation and telomere length in cholesteatoma, 29 cholesteatoma
      samples and 9 squamous cell carcinomas were analyzed for telomerase activity and
      telomere length. In addition, the rate of apoptosis was determined in both
      groups, using the TdT-mediated dUTP nick end labeling technique. RESULTS: As
      previously described, a high proportion of squamous cell carcinoma exhibited
      telomerase activity (6/9, 66%). By contrast, a significantly lower rate of
      telomerase activity was found in cholesteatoma samples (1/29, 3.4%, p = 0.0002).
      Despite the differences in telomerase activity, the telomere length was similar
      in cholesteatoma (mean length 7.43 kb) and in squamous cell carcinoma (mean
      length 7.99 kb; difference not significant, p = 0.1364). The low rate of
      telomerase activity in cholesteatoma was accompanied by significantly higher
      rates of apoptosis in cholesteatoma (mean 30%) compared with squamous cell
      carcinoma tissue (mean 3%, p = 0.0031). CONCLUSIONS: Taken together, these data
      show that telomerase activation is a rare event in cholesteatoma and that the
      absence of telomerase activity is accompanied by high rates of apoptosis in
      cholesteatoma. It is proposed that the absence of telomerase limits the
      proliferative capacity of cholesteatoma by induction of apoptosis, whereas the
      presence of telomerase allows immortal growth of squamous cell carcinoma.

PMID- 12218638
TI  - Transtympanic electrocochleography: a 10-year experience.
AB  - OBJECTIVE: To report the authors' experience with transtympanic
      electrocochleography during the past 10 years. STUDY DESIGN: Retrospective case
      review. SETTING: Otology/neurotology referral center. PATIENTS: Transtympanic
      electrocochleography was performed on 2,421 ears of 2,140 patients from May 1990
      to April 2000. INTERVENTION: Clicks and tonebursts were used in
      electrocochleography testing. Summating potential/action potential ratio was
      calculated. Action potential latency shift by rarefaction and condensation clicks
      was measured. Cochlear microphonic was recorded. MAIN OUTCOME MEASURE: An
      enlarged summating potential/action potential ratio (>0.40), broadened action
      potential waveform (>3 msec) or prolonged action potential latency shift (>0.2
      msec) was considered to be indicative of endolymphatic hydrops. The presence of
      cochlear microphonic indicated hair cell survival. RESULTS: In response to
      clicks, an enlarged summating potential/action potential ratio was found in 76.1%
      of ears and a broadened action potential waveform in 70%. Either an enlarged
      summating potential/action potential ratio or a broadened action potential
      waveform was observed in 78.4% of ears. In response to tonebursts, an enlarged
      summating potential/action potential ratio was found in 64.8%. The combined use
      of clicks and tonebursts yielded an enlarged summating potential/action potential
      ratio in 81.7%. Electrocochleography using tonebursts had the advantage of
      frequency selectivity. A prolonged action potential latency shift was found in
      62.2% of ears with Meniere's disease. A significant association between an
      enlarged summating potential/action potential ratio and an action potential
      latency shift was noted (chi = 5.357, p = 0.021). An enlarged summating
      potential/action potential ratio was found 71% in Stage 1 of Meniere's disease,
      82% in Stage 2, 85% in Stage 3, and 90% in Stage 4 (chi = 19.442, p = 0.000). An
      enlarged summating potential/action potential ratio was associated with the
      duration of the disease, 43% in the under 1-year group, and 100% in the more than
      30-years group (chi = 33.555, p = 0.000). A large cochlear microphonic was
      present in 69% of ears with hearing levels greater than 40 dB. CONCLUSION:
      Transtympanic electrocochleography using clicks and tonebursts is a reliable test
      to detect the presence of endolymphatic hydrops in Meniere's disease. A prolonged
      action potential latency shift evoked by rarefaction and condensation clicks is a
      useful addition to the application of electrocochleography in the diagnosis of
      Meniere's disease.

PMID- 12218639
TI  - Manifestations of otosyphilis as visualized with computed tomography.

PMID- 12218640
TI  - Isolated squamous cell carcinoma of the tympanic membrane.

PMID- 12218641
TI  - Two lessons on slang.

PMID- 12218642
TI  - Statins in the prevention and treatment of Alzheimer disease.
AB  - Vascular risk factors such as hypertension and hypercholesterolemia during
      midlife increase the risk for Alzheimer's disease (AD). Treatment of
      hypercholesterolemia and other vascular risk factors may have great implications
      in the prevention of AD. Recent findings illustrate that the sterol metabolism in
      the brain is an active process, well controlled and regulated by 24-hydroxylase,
      an enzyme that is uniquely expressed in the brain. The use of statins in ischemic
      heart disease (IHD) has proven to be a phenomenal advance in pharmacological
      disease prevention and treatment. A growing body of evidence, suggest that
      statins exhibit additional benefits that are independent of their cholesterol
      lowering actions. Statin treatment has also considerable effect in prevention of
      ischemic stroke. In animal models of ischemic stroke, statins have proven to
      reduce infarct size through up-regulation of endothelial nitric oxide synthases.
      Data from recent observational studies have revealed a potential role for statins
      in prevention of AD. The following review comments the processes leading to
      dementia including the involvement of cholesterol regulation, cerebral
      circulation and inflammation in development of dementia. The mechanisms by which
      statins may be beneficial in controlling these processes is discussed.

PMID- 12218643
TI  - Effect of Alzheimer disease on the cost of treating other diseases.
AB  - The authors' objective is to determine the effect of diagnosed Alzheimer disease
      (AD) on cost to Medicare of treating other diseases. Using the 1994 National Long
      Term Care Survey merged with Medicare claims and death data, the authors assessed
      the relative cost to Medicare of covering beneficiaries over 1994-1995 with
      diagnosed AD relative to other elderly population. They focused on
      hospitalizations during 1994-1995 for hip fracture, stroke, coronary heart
      disease, congestive heart failure, and pneumonia. The authors determined whether
      differences in Medicare payments by AD status mainly reflected differences in
      rates of occurrence of hospitalizations for the five primary diagnoses, other
      primary diagnoses, or death during 1994-1995 or in spending given the adverse
      events. During 1994-1995, an average of $15,700 was spent by Medicare, per
      person, for those with diagnosed AD, nearly twice the amount spent on others. The
      difference in Medicare payments was attributable to more adverse events occurring
      to AD group. Such persons had higher death rates than other elderly population
      (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.07-1.62), higher
      hospitalization rates for hip fracture (OR, 1.96; 95% CI, 1.34-2.87), stroke (OR,
      1.71; 95% CI, 1.10-2.68), pneumonia (OR, 1.46; 95% CI, 1.07-1.99), and for other
      reasons than the five conditions (OR, 1.65; 95% CI, 1.38-1.98), but they also had
      lower hospitalization rates for the cardiac diseases. There were no differences
      in Medicare payments according to AD diagnosis, controlling for frequency of
      deaths, hospitalizations, and other factors. Persons with diagnosed AD cost
      Medicare more because of more adverse health events rather than in intensity of
      care, given event occurrence.

PMID- 12218644
TI  - Relationships among cerebrospinal fluid biomarkers in dementia of the Alzheimer
      type.
AB  - Cerebrospinal fluid (CSF) contains proteins known to be involved in the
      pathogenesis of Alzheimer disease (AD), including amyloid-related proteins, tau
      protein and apolipoprotein E. While the CSF concentrations of these proteins have
      been compared in subjects with and without dementia of the Alzheimer type (DAT),
      they have not been simultaneously assessed in carefully staged DAT subjects and
      control subjects to examine correlations among them. In this study, CSF
      concentrations of soluble amyloid precursor protein (sAPP), two forms of beta
      amyloid protein (Abeta and Abeta ), tau, and apolipoprotein E were assessed in
      subjects with (n = 33) and without (n = 11) DAT. Direct correlations were found
      between CSF concentrations of sAPP and tau and Abeta, and between apolipoprotein
      E and Abeta within the DAT subjects and within the combined group of DAT and
      control subjects. A weak inverse correlation was also found between CSF
      concentrations of tau and Abeta within the combined group of DAT and control
      subjects. Moreover, increased severity of dementia was correlated with increased
      CSF tau concentrations and decreased sAPP and Abeta concentrations. Increased CSF
      concentrations of tau significantly discriminated DAT and control subjects, as
      did the ratios of tau to Abeta and tau to Abeta(1-42).

PMID- 12218645
TI  - Peripheral blood abnormalities in Alzheimer disease: evidence for early
      endothelial dysfunction.
AB  - Clinical and epidemiologic studies demonstrate that vascular risk factors may be
      involved in Alzheimer disease (AD). To evaluate whether vascular abnormalities
      are an early feature of AD, several parameters of coagulation and fibrinolysis
      were assessed. Thirty patients with mild AD and 30 age-matched control subjects
      entered the study. All subjects performed a standardized clinical and laboratory
      protocol. Persons with vascular risk factors and systemic diseases were excluded.
      AD patients present significant increased levels of thrombomodulin (p < 0.0001)
      and sE-selectin (p < 0.03). In contrast, no difference was found between the two
      diagnostic groups in the levels of beta-thromboglobulin, prothrombin fragment
      1+2, fibrinogen, and von Willebrand factor. No other association but diagnosis
      was found with thrombomodulin and sE-selectin. These findings suggest that
      endothelial dysfunction is an early event in AD patients.

PMID- 12218646
TI  - Are peripheral blood cells from patients with Alzheimer disease more sensitive to
      apoptotic stimuli?
AB  - One of the reasons for the increased susceptibility to infections in patients
      with Alzheimer disease may be enhanced apoptotic death of their peripheral
      leukocytes. If this is the case, the enhanced apoptosis may be due to components
      in the patients' sera or to an increased sensitivity of the cells to apoptotic
      stimuli. To examine this possibility, the percentage of apoptotic cells in the
      peripheral blood mononuclear cells (PBMC) from 12 patients with Alzheimer disease
      was compared with that of 12 age-matched non-demented persons and 12 middle-aged
      healthy control subjects. In addition, the effect of sera from subjects in the
      three groups on the apoptosis, interleukin (IL)-1beta, IL-2, IL-6, IL-10, and
      tumor necrosis factor (TNF)alpha production by peripheral blood cells from
      healthy control subjects was examined. It was found that the percentage of
      apoptotic PBMC from patients with Alzheimer disease was higher than that from the
      remaining two groups. However, incubation of control cells with sera from
      patients with Alzheimer disease and non-demented elderly persons did not affect
      the number of apoptotic cells. Sera from patients with Alzheimer disease and non
      demented elderly subjects caused an increase in IL-2 and a decrease in IL-10
      production by PBMC from middle-aged control subjects but did not affect IL-1beta,
      IL-6, and TNFalpha secretion, indicating alterations of the immune system related
      to aging.

PMID- 12218647
TI  - White matter lesions, quantitative magnetic resonance imaging, and dementia.
AB  - The authors performed quantitative and qualitative image analysis on a sample of
      the elderly population of Cache County, Utah, relating neuroimaging findings to
      Mini-Mental Status Examination (MMSE) scores and the presence of the
      apolipoprotein E epsilon4 allele. Neuroimaging measures included white, gray, and
      hippocampal volumes; a ventricle-to-brain ratio (VBR); and qualitative ratings of
      white matter lesions (WMLs) in the periventricular (PV) and centrum semiovale
      (CS) regions. Subjects included 85 persons with possible and probable Alzheimer
      disease (AD), 21 with vascular dementia (VaD), 30 with cognitive symptoms
      classified as mild/ambiguous (M/A), a heterogenous group of 39 non-AD or VaD
      subjects but diagnosed with some form of neuropsychiatric disorder ("Mixed
      Neuropsychiatric" group), and 20 normal control subjects aged 65 years or older.
      Controlling for age, sex, and length of disease, the authors found that AD and
      VaD subjects differed significantly from control subjects on WMLs, but only the
      VaD subjects significantly differed from M/A subjects. The two dementia groups
      also displayed, as expected, significant cerebral atrophy. The WMLs generally
      increased with age and severity of dementia. PV WMLs were significantly but only
      modestly associated with white matter volume loss and greater impairment on the
      MMSE. Modest correlations were also present between the quantitative measures of
      cerebral structure and MMSE performance. However, when degree of cerebral atrophy
      was controlled by using the VBR measure, WML effects on MMSE performance became
      nonsignificant, with the only significant relationship remaining being that
      between hippocampal volume and MMSE performance. There were no significant
      qualitative or quantitative findings related to presence of the epsilon4 allele
      and MMSE performance. The role of WMLs in aging and dementia is discussed.

PMID- 12218648
TI  - Diagnosing dementia in primary care: the accuracy of informant reports.
AB  - In the diagnosis of dementia, information obtained from informants or proxies is
      important; however, little is known about the circumstances under which
      informants' reports lack accuracy. This study compares informant reports of
      cognitive status against psychometric tests to identify the degree of, and
      factors associated with, discrepant reporting. Four areas of patient cognitive
      ability were examined: memory of recent events, ability to remember a short list
      of items after a delay, language/naming abilities, and working memory. Primary
      care practitioners recruited 248 community-dwelling patients aged 75 years or
      more or aged 50-74 years with suspected memory complaints; 248 friends or
      relatives acted as informants. More than half of the informants (60%) gave
      responses consistent with psychometric testing. Informants who underreported
      patient difficulties tended to report on patients who were diagnosed as having
      subclinical dementia, were less educated, and had poorer remote memory.
      Informants who overreported difficulties were more likely to report on those
      diagnosed with dementia. While informant accounts are critical for the assessment
      of dementia, we found that in 40% of cases these reports may be inaccurate,
      particularly when the patient has low education and poor remote memory or when
      overall cognitive difficulties are mild.

PMID- 12218649
TI  - Discourse changes in early Alzheimer disease, mild cognitive impairment, and
      normal aging.
AB  - The purpose of this study was to determine the sensitivity of discourse gist
      measures to the early cognitive-linguistic changes in Alzheimer disease (AD) and
      in the preclinical stages. Differences in discourse abilities were examined in 25
      cognitively normal adults, 24 adults with mild probable AD, and 20 adults with
      mild cognitive impairment (MCI) at gist and detail levels of discourse
      processing. The authors found that gist and detail levels of discourse processing
      were significantly impaired in persons with AD and MCI as compared with normal
      control subjects. Gist-level discourse processing abilities showed minimal
      overlap between cognitively normal control subjects and those with mild AD.
      Moreover, the majority of the persons with MCI performed in the range of AD on
      gist measures. These findings indicate that discourse gist measures hold promise
      as a diagnostic complement to enhance early detection of AD. Further studies are
      needed to determine how early the discourse gist deficits arise in AD.

PMID- 12218650
TI  - Serum creatinine levels correlate with plasma amyloid Beta protein.
AB  - The authors investigated the effect of renal function on plasma amyloid beta
      protein (Abeta) by analyzing the relationship between creatinine (Cr) and Abeta40
      or Abeta42 in plasma from 59 normal control subjects (NC) and 220 Alzheimer
      disease (AD) patients. In all 279 subjects, Cr was significantly associated with
      Abeta40 (p < 0.001) and Abeta42 (p < 0.01), accounting for 7.3% and 3.1% of
      shared variance, respectively. Significant associations were also present in NC
      and AD groups separately. These results indicate that it may be useful to
      consider Cr levels when measuring plasma Abeta.

PMID- 12218651
TI  - Rapid detection of protein aggregates in the brains of Alzheimer patients and
      transgenic mouse models of amyloidosis.
AB  - Extracellular and/or intracellular aggregates are pathological features of many,
      if not all, neurodegenerative diseases. In Alzheimer disease (AD), extracellular
      aggregates of beta-amyloid (Abeta) and intracellular aggregates of tau or a
      synuclein are key diagnostic markers of the disease. We report here a method to
      rapidly detect these protein aggregates that relies on size exclusion filtration
      and immunostaining of trapped material, a method termed filter trapping. We
      demonstrate that aggregated forms of Abeta and tau are readily trapped in 0.22
      microm cellulose acetate filter membranes, which can then be immunostained with
      specific antibodies in a manner similar to the standard immunoblot. Coupling this
      method with serial dilution permits a rapid assessment of relative aggregate
      burden.

PMID- 12218652
TI  - Abeta deposition does not cause the aggregation of endogenous tau in transgenic
      mice.
AB  - In Alzheimer disease, the extracellular deposition of beta-amyloid (Abeta) in the
      brain is accompanied by the intracellular accumulation of aggregated forms of
      hyperphosphorylated tau. In developing animal models of AD, the authors and
      others have been able to reproduce extracellular amyloid pathology in the brains
      of mice by expressing mutant amyloid precursor proteins (APP). The co-expression
      of APP with mutant presenilin leads to a dramatic acceleration in Abeta
      deposition, leading to very high amyloid burdens in mice. In the current study,
      the authors have examined whether the brains of mice with high burdens of amyloid
      deposition also contain aggregated forms of tau, using a cellulose acetate filter
      trap assay. Although discrete accumulations of phosphorylated tau
      immunoreactivity were apparent in neurites proximal to cored deposits of Abeta,
      little if any of this tau was in a SDS-resistant state of aggregation. By
      contrast, the brains of AD patients contained large amounts of aggregated tau.
      Overall, this study demonstrates that, in mice, deposition of Abeta does not
      cause endogenous tau to aggregate.

PMID- 12218653
TI  - Utility-weighted measures of quality of life in Alzheimer disease.

PMID- 12218654
TI  - Implications of multifactorial inheritance for identification of genetic
      mechanisms in major psychiatric disorders.

PMID- 12218655
TI  - Strategies for medium-throughput automated genotyping methods.
AB  - The need to genotype large numbers of individuals has assumed a great scientific
      and commercial importance in recent years. This has been mirrored by the
      requirement for and development of technologies for automating sample
      preparation. In the present article, we describe strategies for the automation of
      aspects common to many genotyping strategies. These include genomic DNA
      extraction, upstream polymerase chain reaction (PCR) amplification, post-PCR
      sample purification and downstream sequencing and/or primer extension of purified
      PCR products.

PMID- 12218656
TI  - Single nucleotide polymorphism detection: allelic discrimination using TaqMan.
AB  - Candidate gene studies are one of the most widely used approaches in the
      dissection of the genetic basis of disease. High-throughput methods for
      genotyping single nucleotide polymorphisms (SNPs) are necessary to perform large
      scale association studies. We describe the use of the TaqMan or 5' nuclease
      allelic discrimination assay for genotyping polymorphisms of the collagen I alpha
      1 (COLIA1) and vitamin D receptor (VDR) genes. The basis for the assay is an
      allele specific oligonucleotide probe, labelled with a fluorescent reporter dye
      and a quencher dye, which is cleaved during the amplification process generating
      an increase in the intensity of fluorescence related to the accumulation of PCR
      product which is measured directly in the reaction well. Suitable for the
      discrimination of alleles differing by a single base change, this technique is
      robust, accurate, cost effective, and sufficiently high-throughput for a medium
      sized laboratory performing association analyses.

PMID- 12218657
TI  - Major psychiatric disorders and the serotonin transporter gene (SLC6A4): family
      based association studies.
AB  - The serotonin transporter (5-HTT) is a suitable candidate gene to test for
      involvement in the pathogenesis of major psychiatric disorders. We used the
      method of family-based controls to test for association between disease and a
      variable number tandem repeat (VNTR) in intron 2 of the gene, which has received
      support for involvement in the pathogenesis of several psychiatric disorders. We
      analysed 413 proband-parent trios of Bulgarian origin: 266 had a schizophrenic
      proband, 103 had a bipolar proband and 44 had a schizoaffective proband. The
      results were analysed using the extended transmission disequilibrium test.
      Possible effects of different alleles on certain clinical variables were examined
      by correlation analysis. Three alleles were detected: STin2.9, STin2.10 and
      STin2.12. None of the three diagnostic samples showed preferential transmission
      of alleles that reached conventional levels of statistical significance. We could
      not confirm previous results that STin2.12 allele increases susceptibility to
      bipolar disorder type I. The rare STin2.9 showed a non-significant trend for
      preferential transmission in the sample as a whole: 18 transmitted versus 11 non
      transmitted (P = 0.2). The VNTR polymorphism in the 5-HTT gene does not appear to
      be a major risk factor for increasing susceptibility to major psychiatric
      disorders.

PMID- 12218658
TI  - Antisocial alcoholism and serotonin-related polymorphisms: association tests.
AB  - Central serotonin dysfunction appears to be related to a subtype of alcoholism
      with antisocial impulsive features (type II; antisocial alcoholism). The
      serotonergic deficit may be associated with greater impulsivity, which in turn
      facilitates both alcohol dependence and antisocial behavior. The present study
      tested association of antisocial impulsive alcoholism with candidate genes
      related to serotonergic neurotransmission, using families. Eight markers were
      assayed using polymerase chain reaction: tryptophan hydroxylase (intron 7), the
      serotonin transporter SLC6A4 (VNTR 9/12), HTTLPR, the three serotonin receptor
      types HTR1B (G861C), HTR2A (T102C) and HTR2C (Cys23Ser), monoamine oxidase A
      (T1460C), and (CA)(n). Eligible probands had early age of onset of alcoholism,
      child conduct disorder, and two or more symptoms of adult Antisocial Personality
      Disorder. This sample included 35 probands, their parents, and some siblings (n =
      116). Association tests were conducted using the Haplotype Relative Risk method
      for antisocial alcoholism diagnosis and the George-Elston regression method (the
      S.A.G.E. program ASSOC) for quantitative antisocial alcoholism severity.
      Haplotype Relative Risk analyses were not significant at the 0.05 level for any
      of the markers. Trends suggestive for future research occurred for tryptophan
      hydroxylase and HTR2A. Quantitative ASSOC analyses showed significant marker
      effects (P < 0.05) for both monoamine oxidase A markers, which were in linkage
      disequilibrium. Antisocial alcoholism symptom severity was higher with monoamine
      oxidase A C homozygotes or hemizygotes, indicating that low monoamine oxidase
      activity may be important. Future studies are needed to examine joint and
      interactive effects of serotonin-related markers.

PMID- 12218659
TI  - Genetic polymorphisms and cerebrospinal fluid levels of tissue inhibitor of
      metalloproteinases 1 in sporadic Alzheimer's disease.
AB  - Tissue inhibitor of metalloproteinases 1 (TIMP-1) inhibits several proteinases
      including a disintegrin and metalloproteinase 10 (ADAM10), a major alpha
      secretase that cleaves the beta-amyloid precursor protein within its
      amyloidogenic Abeta domain. The gene encoding TIMP-1 (TIMP 1) maps to the short
      arm of the X chromosome, in a region previously suggested as conferring genetic
      susceptibility for Alzheimer's disease (AD). To determine whether genetic
      variability of TIMP 1 contributes to the pathogenesis of AD, we analysed one
      single nucleotide polymorphism within TIMP 1 and one single nucleotide
      polymorphism in the 5'-untranslated region of TIMP 1 in patients with AD and
      control subjects from two independent and ethnically different populations. We
      did not observe any association between TIMP 1 genotypes and the diagnosis of AD
      in men or women. We also measured TIMP-1 protein levels in the cerebrospinal
      fluid of patients with AD, healthy control subjects, and patients with other
      neurological disorders. TIMP-1 levels were similar in all groups. In addition, no
      significant differences were observed after stratification for TIMP 1 genotypes.
      Our data show that neither genetic variability nor protein levels of TIMP-1 are
      associated with AD.

PMID- 12218660
TI  - No association between polymorphisms in the serotonin transporter gene and
      susceptibility to cocaine dependence among African-American individuals.
AB  - Genetic research of cocaine abuse has been relatively limited among the African
      American population. Since the serotonin transporter (5HTT) may be involved in
      modulating effects of cocaine, we investigated whether allelic variants of the
      5HTT gene may confer susceptibility to cocaine dependence among African-American
      individuals. One hundred and fifty-six cocaine-dependent subjects and 82 controls
      were studied. Polymerase chain reaction-based genotyping of a variable-number
      tandem-repeat (VNTR) marker yielded three alleles designated 12, 10 and 9.
      Genotype and allele frequencies were compared using chi-square analyses. We found
      no differences between subjects and controls with respect to genotype
      distribution (cocaine: 12/12 = 50%, 10/12 = 35.3%, 10/10 = 13.5%, 9/12 = 1.3%;
      controls: 12/12 = 42.7%, 10/12 = 39.0%, 10/10 = 17.1%, 9/12 = 1.2%). Similarly,
      allele frequencies of the VNTR marker did not differ between the two groups
      (cocaine: 12 = 68.3%, 10 = 31.1%, 9 = 0.6%; controls: 12 = 62.8%, 10 = 36.6%, 9 =
      0.6%). Our findings do not seem to support a relationship between VNTR
      polymorphisms and cocaine dependence among African-American patients. Further
      studies involving larger samples are required to confirm our results.

PMID- 12218661
TI  - Serotonin transporter genetic polymorphisms and harm avoidance in the Chinese.
AB  - The association for the harm avoidance (HA) dimension, as assessed by the
      Tridimensional Personality Questionnaire (TPQ), and the serotonin-transporter
      genetic polymorphisms has been investigated with controversial results. The aim
      of the present study was to replicate this investigation and to establish the
      association for a Chinese population. Two polymorphisms of the serotonin
      transporter (5HTT-LPR, serotonin transporter-linked polymorphism region; 5HTT
      VNTR, variable number tandem repeat polymorphism in intron 2 of the serotonin
      transporter gene) were determined for 192 healthy Han Chinese who had completed
      the TPQ. No significant differences were demonstrated for TPQ HA scores,
      including the sub-scales, for subjects with different 5HTT-LPR genotypes. A
      significantly higher HA2 sub-score was demonstrated for subjects carrying the 10
      12 5HTT-VNTR genotype, however, compared with those from the 12-12 genotype
      group, for the male population (P = 0.007). Our findings suggest that the 5HTT
      genetic polymorphism may be associated with HA scores; however, the effect is
      influenced by ethnicity and gender.

PMID- 12218662
TI  - Genetic variant of the histamine-1 receptor (glu349asp) and body weight change
      during clozapine treatment.
AB  - Clozapine treatment frequently causes body weight gain that may impair health and
      may affect patient compliance. While the histamine-1 (H1) receptor may play a
      major role in the mechanism of the clozapine-induced body weight change, we
      tested the relationship between the genetic variant (Glu349Asp) of the H1
      receptor and the clozapine-induced body weight change. Eighty-eight schizophrenic
      patients treated with clozapine were included in this study. Analysis of body
      weight change after 4 months of clozapine treatment showed no relationship with
      the H1 genotype. Further exploration of the other H1 genotypes and the
      antipsychotic-induced body weight change may help in the understanding of the
      mechanisms of antipsychotic-induced body weight gain and in the choice of
      patient's antipsychotic regimens.

PMID- 12218663
TI  - No association between the dopamine D3 receptor gene and Korean alcohol
      dependence.
AB  - The genes encoding dopamine receptor (DR) subtypes have received considerable
      attention for the past several years as a potential candidate that may affect
      susceptibility to addictive disorder, including alcoholism. The many association
      studies that compared the frequencies of alleles of the dopamine D2 receptor
      (DRD2) gene between alcoholics and control groups have produced results, but some
      have been equivocal. Dopamine D3 receptor genes (DRD3) are in the same class as
      DRD2 but with different pharmacological properties. So we compared the
      distribution of genotypes and frequencies of BalI polymorphism of the DRD3 gene
      in alcoholics and controls to assess the role of the DRD3 gene in Korean
      alcoholism. For this study, 67 male probands from alcoholics and 67 age-matched
      normal male controls were engaged. No evidence for an allelic association was
      found between the A1 allele of DRD3 and alcoholism in a Korean population. These
      results suggest that any role played by this receptor may account for only part
      of the variation in susceptibility to alcoholism.

PMID- 12218664
TI  - Do puerperal psychotic episodes identify a more familial subtype of bipolar
      disorder? Results of a family history study.
AB  - Bipolar women have a marked vulnerability to puerperal psychosis, an episode of
      mania or psychosis following childbirth. We have conducted a family history study
      to examine the question of whether a vulnerability to puerperal episodes of
      illness is a marker for a more familial form of bipolar disorder. A consecutive
      series of 103 bipolar disorder probands were recruited in a lithium clinic and
      given a semi-structured interview, including a detailed family history. For the
      52 female probands, information was also obtained about the relationship of
      episodes to childbirth. The morbid risk of affective disorder in first-degree
      relatives of bipolar women who had suffered an episode of mania, hypomania or
      schizoaffective mania with onset within 6 weeks of childbirth was significantly
      higher than that in relatives of parous bipolar women with no episodes in
      relation to childbirth (P = 0.0077). Despite relatively small numbers, this study
      provides evidence to support the hypothesis that puerperal episodes identify a
      more familial subtype of bipolar disorder.

PMID- 12218666
TI  - A guest editorial: Erb palsy without apparent shoulder dystocia.

PMID- 12218667
TI  - Treatment of the infertile patient with polycystic ovarian syndrome.
AB  - Polycystic ovarian syndrome is associated with infertility due to anovulation
      caused by this disorder. Many treatments can increase both ovulation and
      fertility rates in these women. This is a comprehensive review of the literature,
      with an emphasis on randomized controlled trials of the medical and surgical
      treatment options for women with polycystic ovarian syndrome and infertility.
      Both standard and novel treatments are addressed. In the past, clomiphene citrate
      was the first-line medical treatment for subfertility in these women, followed by
      gonadotropins with or without gonadotropin releasing-hormone agonists for those
      women with clomiphene-resistance. Surgical treatments such as ovarian drilling
      were occasionally added to these regimens. The introduction of the insulin
      sensitizing agents as adjuvants to clomiphene citrate and gonadotropins has
      changed the treatment strategy. The evidence in support of this change will be
      discussed. Data on the use of glucocorticoids, opioid receptor antagonists, and
      antiandrogens as adjuvants to standard therapies, as well as surgical treatments
      such as wedge resection and ovarian drilling will also be discussed. Based upon
      the evidence, medical treatment remains the primary therapy for women with this
      syndrome, especially in light of the recent introduction of insulin-sensitizing
      agents to the treatment armamentarium. These drugs have allowed us to develop
      less aggressive therapies that are safer and easier for women to utilize, and may
      in the future become the primary treatment for women with this syndrome. TARGET
      AUDIENCE: Obstetricians & Gynecologists, Family Physicians Learning Objectives:
      After completion of this article, the reader will be able to explain the
      pathophysiology of PCOS, to list the factors that predispose women to develop
      PCOS, and to outline the treatment regiments for PCOS-associated infertility.

PMID- 12218668
TI  - Preeclampsia. Part 1: clinical and pathophysiologic considerations.
AB  - Preeclampsia-eclampsia is still one of the leading causes of maternal and fetal
      morbidity and mortality. Despite active research for many years, the etiology of
      this disorder exclusive to human pregnancy is an enigma. Recent evidence suggests
      there may be several underlying causes or predispositions leading to the signs of
      hypertension, proteinuria, and edema, findings that allow us to make the
      diagnosis of the "syndrome" of preeclampsia. Despite improved prenatal care,
      severe preeclampsia and eclampsia still occur. Although understanding of the
      pathophysiology of these disorders has improved, treatment has not changed
      significantly in over 50 years. Although postponement of delivery in selected
      women with severe preeclampsia improves fetal outcome to a degree, this is not
      done without risk to the mother. In the United States, magnesium sulfate and
      hydralazine are the most commonly used medications for seizure prophylaxis and
      hypertension in the intrapartum period. The search for the underlying cause of
      this disorder and for a clinical marker to predict those women who will develop
      preeclampsia-eclampsia is ongoing, with its prevention the ultimate goal. This
      review begins with the clinical and pathophysiologic aspects of preeclampsia
      eclampsia (Part 1). In Part 2, the experimental observations, the search for
      predictive factors, and the genetics of this disorder will be reviewed.

PMID- 12218669
TI  - Preeclampsia. Part 2: experimental and genetic considerations.
AB  - Preeclampsia-eclampsia is still one of the leading causes of maternal and fetal
      morbidity and mortality. Despite active research for many years, the etiology of
      this disorder exclusive to human pregnancy is an enigma. Recent evidence suggests
      there may be several underlying causes or predispositions leading to the signs of
      hypertension, proteinuria, and edema, findings that allow us to make the
      diagnosis of the "syndrome" of preeclampsia. Despite improved prenatal care,
      severe preeclampsia and eclampsia still occur. Although understanding of the
      pathophysiology of these disorders has improved, treatment has not changed
      significantly in over 50 years. Although postponement of delivery in selected
      women with severe preeclampsia improves fetal outcome to a degree, this is not
      done without risk to the mother. In the United States, magnesium sulfate and
      hydralazine are the most commonly used medications for seizure prophylaxis and
      hypertension in the intrapartum period. The search for the underlying cause of
      this disorder and for a clinical marker to predict those women who will develop
      preeclampsia-eclampsia is ongoing, with its prevention the ultimate goal. This
      review began with the clinical and pathophysiologic aspects of preeclampsia
      eclampsia (Part 1). Now, in Part 2, the experimental observations, the search for
      predictive factors, and the genetics of this disorder are reviewed.

PMID- 12218671
TI  - Reflections on 9/11.

PMID- 12218675
TI  - Responding to an out-of-hospital emergency.

PMID- 12218676
TI  - Buying time.

PMID- 12218677
TI  - What you can do to decrease catheter-related infections.

PMID- 12218681
TI  - How HIPAA will change your practice.

PMID- 12218682
TI  - Skip the knife: debriding wounds without surgery.

PMID- 12218692
TI  - Agrin in the CNS: a protein in search of a function?
AB  - The extracellular matrix molecule agrin mediates the motor neuron induced
      accumulation of acetylcholine receptors (AChR) at the neuromuscular junction.
      Agrin is also present in the CNS. However, while its spatiotemporal pattern of
      expression is consistent with a function in neuron-neuron synapse formation, it
      also suggests a role for agrin in other aspects of neural tissue morphogenesis.
      Here we review the data supporting these synaptic and non-synaptic functions of
      agrin in the CNS. The results of studies aimed at identifying a neuronal receptor
      for agrin (NRA) and its associated signal transduction pathways are examined.
      Possible roles for agrin in the etiology of diseases affecting the brain are also
      discussed.

PMID- 12218693
TI  - Regional brain activations differ for semantic features but not categories.
AB  - Is human semantic knowledge neurally organised according to either category (e.g.
      living non-living) or attribute type (e.g. perceptual non-perceptual
      information)? Normal subjects were scanned using PET during a novel semantic
      production task, in which they generated either perceptual or non-perceptual
      information in response to names of living or non-living concepts. Analyses of
      blood flow in the temporal lobes revealed no significant differences associated
      with responses to living non-living concepts. Comparisons between retrieval of
      perceptual non-perceptual information, however, revealed significantly greater
      blood flow in left posterior inferior temporal cortex and right fusiform cortex
      associated with perceptual information and in left middle temporal cortex with
      non-perceptual information. These findings support a primarily attribute-based
      neural organisation of semantic knowledge.

PMID- 12218694
TI  - AAV2 vectors mediate efficient and sustained transduction of rat embryonic
      ventral mesencephalon.
AB  - The success of transplantation of human embryonic mesencephalic tissue to treat
      parkinsonian patients is limited by the poor survival of the transplant. We show
      that an AAV2 vector mediates efficient expression of the egfp reporter gene in
      organotypic cultures of freshly explanted solid fragments of rat embryonic
      ventral mesencephalon (VM). We observed early and sustained transgene expression
      (4 days to > or = 6 weeks). Furthermore, rAAV-infected rat embryonic VM
      transplanted in the adult striatum continued to express EGFP for > or = 3 months.
      More than 95% of the transduced cells were neurons. Dopaminergic neurons were
      transduced at low frequency at earlier time points. This method of gene delivery
      could prove useful to achieve local, continuous secretion of neurotrophic factors
      at physiologically relevant doses to treat Parkinson's disease.

PMID- 12218695
TI  - Alcohol and nicotine reduce cell proliferation and enhance apoptosis in dentate
      gyrus.
AB  - It is generally accepted that alcohol and nicotine affect learning ability and
      memory functions, especially in adolescents. In the present study, the effects of
      alcohol and nicotine on cell proliferation and apoptosis in the dentate gyrus of
      young rats were investigated. The results show that cell proliferation is
      suppressed by alcohol and nicotine. Furthermore, alcohol and nicotine increase
      the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling (TUNEL)-positive cells. Based on the results presented in this study, it
      can be suggested that alcohol- and nicotine-related impairment in learning and
      memory functions may be due to alcohol- and nicotine-induced suppression of new
      cell formation and acceleration of apoptosis, especially during adolescence.

PMID- 12218696
TI  - Time-related increase in mitochondrial superoxide production, biomolecule damage
      and antioxidant enzyme activities in cortical astrocyte cultures.
AB  - According to the free radical theory of aging, biological senescence processes
      develop from a general failure to maintain organism's homeostasis, probably due
      to oxidative stress. The brain is particularly susceptible to oxidative damage,
      and astrocytes are chiefly responsible for its antioxidant defense. Here we
      evaluated and compared the enzymatic antioxidant activities, mitochondrial
      superoxide production, and oxidative damage in biomolecule in cortex astrocytes
      from newborn Wistar rats maintained for 10-13 or 40-47 days in culture. We show
      that, besides an increase in antioxidant enzyme activities in matured astrocyte
      cultures, there was an increase in lipoperoxidation and in protein oxidation,
      probably due to an increase in mitochondrial electron transport chain superoxide
      production. This could indicate that the increasing in defense mechanisms was not
      sufficient to avoid oxidative biomolecule damage during maturation.

PMID- 12218697
TI  - Contribution of primary somatosensory area 3b to somatic cognition: a
      neuromagnetic study.
AB  - Interference effects on somatic cognition were compared with those on primary
      magnetic N20m responses. During tactile interference to various sets of digits,
      sensory thresholds for electric middle finger stimulation were measured, and then
      N20m was elicited with the intensity 4 mA above the sensory threshold measured
      without interference. After the recording, subjective magnitudes for the test
      stimuli were reported. Modifications of N20m and above psychophysical measures
      were dependent on the distance between electrically and mechanically activated
      areas. The differential N20m attenuation is considered to be generated within the
      neural circuitry in area 3b consisting of mechanically and electrically activated
      pyramidal neurons. The result indicates that such circuitry plays a fundamental
      role in magnitude estimation of somatic stimuli.

PMID- 12218698
TI  - Differential response to NPY of PVH and dopamine-responsive VMH neurons in
      overweight rats.
AB  - Neuronal responses to neuropeptide Y and dopamine were recorded in brain slices
      of hypothalamic paraventricular (PVH) and ventromedial (VMH) nuclei in normal and
      hyperphagic overweight rats reared in small litters of three pups. NPY
      significantly activated PVH neurons of normal rats, but inhibited neurons of
      overweight rats. In the VMH, a significantly higher coincidence of inhibition
      induced by NPY and dopamine was found in overweight rats. Similar neuronal
      responses were evoked by a NPY Y5 receptor agonist. Effects of NPY could be
      blocked by a Y1 receptor antagonist. The altered response of PVH neurons to the
      feeding-inducing NPY and the increased inhibition by NPY and dopamine in the VMH
      might contribute to the persisting hyperphagia and overweight of postnatally
      overnourished rats.

PMID- 12218699
TI  - Preferential expression of plasmalemmal K-dependent Na+/Ca2+ exchangers in
      neurons versus astrocytes.
AB  - Numerous isoforms of plasmalemmal K-dependent (NCKX) and K-independent (NCX)
      Na+/Ca2+ exchangers are expressed in the brain. The physiological functions of
      each isoform are presently unknown. Therefore, in this study, we compared
      expression of NCKX and NCX transcripts between primary cultures of cerebellar
      granule cells, and astrocytes. Northern blot analysis showed that granule cells
      expressed NCKX2, NCKX3, NCKX4 and NCX3, whereas astrocytes expressed primarily
      NCX1. Consistent with this molecular characterization, a significant fraction of
      45Ca2+ accumulation in Na-loaded granule cells, but not in astrocytes, depended
      on external K+. This is the first demonstration of native NCKX activity in
      neurons derived from the central nervous system. Our data suggest that NCKX
      isoform expression may correspond to the unique Ca2+ homeostasis requirements of
      neurons.

PMID- 12218700
TI  - High glutamate decreases S100B secretion stimulated by serum deprivation in
      astrocytes.
AB  - S100B is a calcium-binding protein expressed and secreted by astrocytes, playing
      a neurotrophic role in neighboring cells. A protective role of the S100B against
      glutamate-induced excitotoxicity has recently been proposed. We investigated
      S100B secretion in rat hippocampal astrocytes exposed to high concentrations of
      glutamate during serum deprivation (stimulated condition) or not (basal
      condition), for 30 min. Glutamate at 1 mM had no effect on basal secretion of
      S100B, but it decreased S100B secretion in serum-deprived astrocytes after 1 h.
      Secretion was inhibited by Rp-cAMPS or H89. In addition, serum deprivation was
      accompanied by a transitory increase of intracellular content of cAMP. Our
      results suggest that high levels of glutamate in a serum-deprived condition could
      impair S100B secretion from hippocampal astrocytes.

PMID- 12218701
TI  - A deficit in the adjustment of grip force responses in schizophrenia.
AB  - Delusions of control in schizophrenia may be due to a deficit in the generation
      of an efference copy, used to distinguish between self generated and externally
      imposed changes in the environment. This hypothesis was tested using a framework
      that differentiated automatic and controlled levels of motor behavior. Subjects
      resisted collisions that were either self or externally imposed. The grip to load
      force correlation (response accuracy) and the overall grip force level used
      (response efficiency) were measured. Controls improved both accuracy and
      efficiency of their grip force responses in self compared to externally imposed
      collisions. Patients improved accuracy but not efficiency of motor response.
      There was no difference between patients with and without delusions of control.
      These results refute the hypothesis of a perturbed efference copy in patients
      with delusions of control. We rather propose that schizophrenia globally
      preserves the automatic level but affects the controlled, more voluntary level of
      motor behavior.

PMID- 12218702
TI  - NMDA and AMPA receptor subunit protein expression in the rat vestibular nucleus
      following unilateral labyrinthectomy.
AB  - We examined the expression of the NR1 and NR2A subunits of the N-methyl-D
      aspartate (NMDA) receptor, and the GluR2 subunit of the alpha-amino-3-hydroxy-5
      methyl-4-isoxazole propionate (AMPA) receptor, in the ipsilateral and
      contralateral vestibular nucleus complexes (VNCs) at 10 h and 2 weeks following
      unilateral vestibular deafferentation (UVD) in rats, in order to directly test
      the hypothesis that the behavioural recovery following UVD ('vestibular
      compensation') is associated with an up-regulation of NMDA receptors. We found no
      significant changes in NR1 or NR2A expression at 10 hs or 2 weeks post-op.
      compared to sham and anesthetic controls. We did find a significant (p < 0.01 and
      p < 0.05) increase in GluR2 expression in both VNCs at 10 h but not 2 weeks post
      op. compared to sham and anesthetic controls; however, comparison over time post
      UVD failed to detect a significant difference, suggesting that it was small and
      transient at best. These results add further evidence to the conclusion that NMDA
      receptors do not undergo up-regulation in the ipsilateral VNC during vestibular
      compensation.

PMID- 12218703
TI  - 5-HT(2C) receptor activation by m-chlorophenylpiperazine detected in humans with
      fMRI.
AB  - Functional brain imaging using selective drug probes offers the opportunity to
      investigate regional neuronal activation linked to receptor stimulation or
      inhibition. In a placebo-controlled, balanced order design in eight male
      volunteers, the 5-HT(2c) agonist, m-chlorophenylpiperazine (mCPP) increased blood
      oxygen level dependent (BOLD) signal in the hypothalamus, caudate, pallidum,
      amygdala and pyriform cortex, anterior cingulate gyrus and choroid plexus (p <
      0.001 uncorrected), areas with high density of 5-HT(2c) receptors. Activation in
      the hypothalamus correlated significantly with the prolactin response (p < 0.05
      small volume corrected). In a subsequent Go/NoGo task, mCPP enhanced activation
      in right lateral orbitofrontal cortex (p < 0.05 small volume corrected). These
      findings suggest that pharmacoMRI is a potentially powerful tool for
      investigating neurotransmitter function in humans.

PMID- 12218704
TI  - Presenilin-1 mutations alter K+ currents in the human neuroblastoma cell line, SH
      SY5Y.
AB  - Mutations in presenilin 1 (PS1) are the major cause of autosomal dominant
      Alzheimer's disease. We have measured the voltage-gated K+ current in the human
      neuroblastoma cell line SH-SY5Y using whole-cell patch-clamp. When cells were
      stably transfected to over-express PS1, no change in K+ current was observed.
      However, over-expression of a deletion mutation (deltaE9) in PS1 led to a
      decreased K+ current. These changes were channel specific since no change in the
      Na+ current could be observed in the same cells. Confocal microscopy revealed
      that the K(V)3.1 K+ channel subunit had a diminished plasma membrane distribution
      when the deltaE9 over-expressing cells were compared to control cells.
      Intracellular retention of Kv3.1 is consistent with the notion that PS1 can
      modulate the activity and trafficking of ion channels in central neurones and
      implicates a compromise in electrical signalling as an underlying factor in the
      pathogenesis of familial Alzheimer's disease.

PMID- 12218705
TI  - Effect of prostaglandins on parasympathetic neurons in the rat lumbosacral spinal
      cord.
AB  - Prostaglandin E(2)(PGE(2)) elicits a variety of effects by activating four
      subtypes of receptors, EP1, EP2, EP3 and EP4. We examined receptor subtypes
      mediating the effects of PGE(2) on parasympathetic preganglionic neurons that
      regulate the activity of pelvic visceral organs. In tonic parasympathetic
      preganglionic neurons in neonatal rat spinal slices, PGE(2) increased the firing
      frequency to depolarizing current pulses, induced after-discharges and inhibited
      spike after-hyperpolarization. PGE(2) did not affect phasic preganglionic
      neurons. An EP1 agonist inhibited after-hyperpolarizations and induced after
      discharges, whereas EP4 agonist reduced after-hyperpolarization and increased
      evoked firing but did not induce after-discharges. EP2 and EP3 agonists were
      inactive. These results indicate that PGE(2) acting via EP1 and/or EP4 receptors
      modulates the excitability and/or excitatory synaptic input to tonic
      parasympathetic preganglionic neurons.

PMID- 12218706
TI  - On-line versus off-line vestibular-evoked control of goal-directed arm movements.
AB  - The present study tested whether vestibular input can be processed on-line to
      control goal-directed arm movements towards memorized visual targets when the
      whole body is passively rotated during movement execution. Subjects succeeded in
      compensating for current body rotation by regulating ongoing arm movements. This
      performance was compared to the accuracy with which subjects reached for the
      target when the rotation occurred before the movement. Subjects were less
      accurate in updating the internal representation of visual space through
      vestibular signals than in monitoring on-line body orientation to control arm
      movement. These results demonstrate that vestibular signals contribute to motor
      control of voluntary arm movements and suggest that the processes underlying on
      line regulation of goal-directed movements are different from those underlying
      navigation-like behaviors.

PMID- 12218707
TI  - Semantic factors influence multisensory pairing: a transcranial magnetic
      stimulation study.
AB  - It is traditionally assumed that temporal and spatial factors determine whether
      information provided by different sensory modalities is combined in a single
      percept. However, neuropsychological reports of selective damage to audio-visual
      integration and recent neurophysiological results suggest that semantic factors
      related to the content of the stimuli could also play a role. As a means of
      extending evidence provided by neuropsychological dissociations we set up a
      direct comparison of two kinds of audio-visual pairs with different semantic
      properties and used transcranial magnetic stimulation (TMS). We investigated the
      selective impact of TMS on two kinds of audio-visual pairings presented under
      identical spatio-temporal conditions (face-voice and tone-shape pairings). Our
      results show that TMS applied over the left posterior parietal cortex at 200 ms
      disrupted audio-visual integration for the tone-shape pairings but not for the
      face-voice ones. Our data are consistent with neuropsychological findings and
      indicate that besides the well-known dimensions of spatial and temporal
      contiguity, content is an important determinant of audio-visual integration. Our
      study also illustrates the usefulness of TMS for addressing the role of semantic
      factors in multi-sensory perception

PMID- 12218708
TI  - Repeated sucrose access influences dopamine D2 receptor density in the striatum.
AB  - A decrease in D2 dopamine receptor subtype (D2R) binding in the striatum has been
      reported in obese individuals and drug addicts. We examined D2R density in the
      striatum of food-restricted rats that had contingent access to food with
      different incentive values. Results showed that animals receiving limited access
      to 0.3 M sucrose paired 2 h with a chow meal for 7 days had a significantly lower
      D2R binding in nucleus accumbens shell and dorsolateral striatum compared with
      animals that had limited access to chow. There was no differential binding,
      however, in the accumbens core in any of the groups. These findings indicate that
      feeding conditions and sucrose intake influence D2R density specifically in
      subregions of the striatum.

PMID- 12218709
TI  - Cerebral blood flow changes in depressed patients after treatment with repetitive
      transcranial magnetic stimulation: evidence of individual variability.
AB  - OBJECTIVE: To elucidate the neural mechanisms of depression. BACKGROUND: Despite
      extensive study, the neurophysiology of the brain's state(s) corresponding to
      depression remains uncertain. METHODS: HMPAO single photon emission computed
      tomographic (SPECT) scans were obtained from eight adults diagnosed with major
      depression resistant to medication (average age 51 years; 4 men) before and
      immediately after 10 days of 20 Hz repetitive transcranial magnetic stimulation
      (rTMS) (2000 stimuli/daily 30' treatment). To maximize the likelihood that SPECT
      scans reflected the state of depression, rather than uncontrolled responses of
      patients to poorly constrained environments, HMPAO was administered while
      subjects performed a simple task involving continuous monitoring of the direction
      of a large arrow on a computer screen and continuously tapping with the left or
      right index finger according to the direction of the arrow. Mean baseline Beck
      Depression Inventory (BDI) score was 27.4 (SD = 8.3) and mean posttreatment BDI
      score was 17.5 (SD = 8.5). RESULTS: Treatment responders (defined by reduction in
      BDI score of > or = 30%) had significantly less pretreatment blood flow in the
      left amygdala compared with nonresponders. Responders demonstrated two patterns
      of change in regional blood flow with treatment: a reduction in orbitofrontal
      blood flow and/or a reduction in anterior cingulate blood flow. Nonresponders did
      not demonstrate any regional changes in blood flow with treatment. CONCLUSIONS:
      These results suggest that there may be either more than one state of depression,
      or that depression may be associated with more than one pattern of psychologic
      activity, which in turn defines the depressive experience for individual
      patients.

PMID- 12218710
TI  - An informant-based assessment of apathy in Alzheimer disease.
AB  - OBJECTIVE: To standardize a new rating scale for the assessment of apathy in
      Alzheimer disease (AD) and report on its reliability, structure, and relation to
      other clinical features of AD. BACKGROUND: apathy is a common prominent
      behavioral syndrome accompanying AD and is associated with excess disability and
      increased caregiver burden. Current instruments for the assessment of apathy in
      AD do not explicitly and systematically attempt to differentiate limited activity
      and engagement due to lack of interest from inability or longstanding, premorbid
      personality traits. The present assessment, the Dementia Apathy Interview and
      Rating (DAIR), was developed taking these discriminations into account in
      question construction and interview format. METHODS: One hundred participants
      (50% women) in the University Memory and Aging Center Research Registry with
      Probable or Possible AD (by NINCDS-ADRDA criteria) were assessed through
      caregiver interview or direct patient assessment for apathy, depression, and
      severity of cognitive and functional deficits. Item distribution characteristics,
      factor analysis, and evaluation of reliability were used to develop the final
      item set for the DAIR, and correlations with other measures were examined.
      RESULTS: A 16-item unidimensional apathy scale with excellent internal
      consistency (alpha = 0.89) and temporal reliability ( = 0.85 over 2 months) was
      developed. Individual differences in apathy on the DAIR were unrelated to
      dysphoria. Apathy was significantly associated with functional and cognitive
      impairment, while depression was not. CONCLUSIONS: The DAIR is a reliable
      informant-based assessment of apathy in persons with AD. Although apathy is
      assessed with respect to behaviors within the repertoire of patients, this
      behavioral syndrome remains associated with more severe deficits in cognitive and
      adaptive functioning. Associations between depression and dementia severity
      reported in some studies may reflect the confounding of apathy and depression in
      some assessment instruments.

PMID- 12218711
TI  - Cognitive correlates of apathy in traumatic brain injury.
AB  - OBJECTIVE: To investigate the relation between apathy and cognitive deficits in
      patients with severe traumatic brain injury (TBI). BACKGROUND: Apathy defined as
      reduced goal-directed behavior due to lack of motivation constitutes a major
      neuropsychiatric symptom following TBI. According to definition, apathy should
      not be associated with global cognitive reduction, but rather with specific areas
      of cognitive dysfunction. METHODS: results from the Apathy Evaluation Scale (AES)
      and a comprehensive neuropsychologic assessment were collected in up to 53
      patients with severe TBI. Neuropsychologic tests were organized in the following
      seven areas of cognitive function: acquisition and memory, attention span,
      executive function, psychomotor speed, verbal skills, nonverbal skills, and motor
      speed. RESULTS: Apathy score was significantly correlated with reduced
      performance on acquisition and memory, psychomotor speed, and executive
      functions. A principal component analysis showed that these specific areas of
      cognitive functions clustered together with the cognitive dimension of apathy,
      not with behavioral or emotional aspects of apathy. CONCLUSIONS: Apathy is
      associated with specific cognitive deficits related to frontal lobe dysfunction.
      The results are in accordance with the definition of apathy and confirm apathy
      cognitive function relationships reported in other neurologic populations.

PMID- 12218712
TI  - Longitudinal personality changes among presymptomatic Huntington disease gene
      carriers.
AB  - OBJECTIVE: To determine whether longitudinal changes in personality as measured
      by the Minnesota Multiphasic Personality Inventory (MMPI) can be detected among
      clinically presymptomatic individuals carrying the expanded Huntington disease
      (HD) allele. BACKGROUND: Emotional symptoms are considered one of the cardinal
      features of HD. However, the literature is replete with conflicting reports of
      psychiatric symptoms in presymptomatic HD gene carriers. METHODS: A longitudinal,
      case-control, double-blind study comparing presymptomatic gene carriers and
      nongene carriers at risk for HD evaluated with an abbreviated MMPI and a
      quantified neurologic rating scale examined an average of 3.7 years apart.
      RESULTS: Presymptomatic gene carriers (PSGC) had a greater increase in
      abnormality over time for the MMPI scales, cynical hostility (repeated-measures
      ANOVA, = 0.04) and irritability (repeated measures ANOVA, = 0.005), when compared
      with the nongene carriers (NGC). Among both the PSGCs and NGCs, no significant
      correlation was found between the number of CAG repeats and the change in MMPI
      score between visits. CONCLUSIONS: This study provides significant evidence for
      increasing irritability and cynical hostility in presymptomatic gene carriers
      before the onset of overt clinical symptoms.

PMID- 12218713
TI  - Visual perceptual functions predict instrumental activities of daily living in
      patients with dementia.
AB  - OBJECTIVE: To assess relations between discrete visual perceptual functions
      commonly affected in patients with neurodegenerative dementia and the performance
      of instrumental activities of daily living (IADL). BACKGROUND: Neuropsychologic
      measures are often used to predict IADL performances in dementia patients. Prior
      studies have focused on the contribution of higher-level memory and executive
      deficits to IADL. The relation between visuoperceptual dysfunction and IADL has
      not been studied systematically. METHODS: Thirty-five elderly patients with
      neurodegenerative disorders, most diagnosed with probable Alzheimer disease,
      participated. Patients completed tasks tapping visual perceptual functions
      believed to be mediated by occipital lobe structures (shape discrimination),
      posterior inferotemporal regions (face, object form, and written word
      discrimination), and the dorsolateral parietal lobe (spatial localization). A
      knowledgeable caregiver rated IADL performance. RESULTS: Object form
      discrimination, but not other visual perceptual functions, correlated
      significantly ( = 0.60) with performances of visually based IADL (e.g.,
      misjudging distances, driving, and recognizing familiar people), but not with
      other IADL, when the variance attributable to dementia severity, language
      disturbance, and other visual perceptual abilities was controlled. CONCLUSIONS:
      In contrast to prior investigations that have focused primarily on relations of
      memory and executive control deficits with IADL in neurologically impaired
      patients, the results of this study highlight the important contribution of
      bilateral inferotemporal visual perceptual systems for the performance of IADL in
      elderly patients with neurodegenerative dementia.

PMID- 12218714
TI  - Neuropsychologic variables in sporadic late-onset Alzheimer disease in patients
      of spanish nationality: a fast and efficient assessment procedure.
AB  - OBJECTIVE: To learn which neuropsychologic tasks are affected in Spanish patients
      with sporadic late-onset Alzheimer Disease and to determine which are more
      relevant to make a diagnosis with minimum cost but without losing accuracy.
      BACKGROUND: The sample used in this study comprised of 88 subjects: 42 subjects
      diagnosed with SLOAD and 46 subjects who, with no family history of dementia at
      the time of examination, showed no type of neurologic or psychiatric disorder;
      neither did they have any record of alcoholism or drug addiction. METHODS: The
      evaluation of each subject in the clinical group consisted of a full neurologic
      examination, a neuropsychologic evaluation with a battery of tests designed for
      this study, and an assessment of mood with the Beck Depression Inventory. The
      battery of neuropsychologic tests used in diagnosing AD was subjected to
      discriminant analysis by the stepwise method, using diagnosis (1 = AD, 2 =
      control) as a dependent variable. The objective of the stepwise method of this
      technique is to select from the set of independent variables those that best
      discriminate between the two groups of the dependent variable, thus, satisfying
      the criterion of parsimony with which greater classifying specificity is obtained
      with a minimum number of variables. RESULTS: The analysis selected the following
      tests as optimum and sufficient: Babcock Story Recall (Delay), Categories
      Completed (Wisconsin), and Remote Memory. CONCLUSIONS: The results of
      discriminant analysis made it possible to obtain a highly significant
      discriminant function. This analysis reduced the initial battery to three tests,
      yielding a sensitivity of 96.6% in the correct diagnostic classification of the
      subjects.

PMID- 12218715
TI  - Obsessive compulsive disorder in huntington disease: a case of isolated
      obsessions successfully treated with sertraline.
AB  - OBJECTIVE: To report about a patient with Huntington disease (HD) in combination
      with obsessions who was successfully treated with a selective serotonin reuptake
      inhibitor. BACKGROUND: Obsessive compulsive disorder (OCD) has rarely been
      reported in association with HD, and little is known about the treatment of
      patients with OCD symptoms and HD. METHODS: We describe a 42-year-old woman who
      experienced isolated obsessive thoughts about killing her neighbor 10 years after
      the onset of her genetically confirmed HD. RESULTS: Sertraline was prescribed at
      a daily dose of 150 mg with a complete remission of obsessive ideas within 4
      weeks of treatment. CONCLUSIONS: The basal ganglia are known to play an important
      role in the pathogenesis of OCD and HD. Thus, it is conceivable that a
      degeneration of the caudate nucleus as in HD may also account for obsessive and
      compulsive symptoms in this disorder. To our knowledge, this is the first report
      about a patient with HD in combination with obsessions alone who was successfully
      treated with a selective serotonin reuptake inhibitor. However, the association
      of OCD with HD warrants further systematic evaluation.

PMID- 12218716
TI  - Whiplash controversy.

PMID- 12218717
TI  - We are what we eat: is this true?

PMID- 12218718
TI  - How does raloxifene reduce fracture risk?

PMID- 12218719
TI  - Variation in nutrient intakes by ethnicity: results from the Study of Women's
      Health Across the Nation (SWAN).
AB  - OBJECTIVE: To use food frequency questionnaires to summarize the macro- and
      micronutrient intakes of women of diverse ethnicity in the Study of Women's
      Health Across the Nation. DESIGN: The Study of Women's Health Across the Nation
      is a multisite, multiethnic, community-based, longitudinal study of midlife women
      at seven geographic locations in the USA. The cohort is made up of participants
      with African, Caucasian, Chinese, Hispanic, and Japanese ethnic backgrounds. The
      Block Food Frequency Questionnaire was modified to accommodate ethnic-specific
      diets and was administered by interview. Descriptive statistics for macro- and
      micronutrient intakes were calculated, and variation in nutrient intakes by
      ethnic group was assessed using multivariable models, with Bonferonni correction
      for multiple comparisons. RESULTS: The crude and energy-adjusted distributions of
      all 28 nutrients studied differed statistically by ethnicity ( < 0.001). In many
      cases the magnitude of the variation was small. For example, the difference
      between the highest and lowest mean energy intakes was approximately 135 kcal
      (African American vs. Hispanic). Other differences were substantial: the energy
      adjusted total fat intake in Chinese women was at least 10% lower than all other
      ethnic groups except the Japanese women (all pair-wise comparisons; < 0.01).
      CONCLUSIONS: Knowledge of variation in nutrient intake is critical to the
      understanding of how diet and health are related. The broad range of nutrient
      intakes reported by these participants will permit exploration of the
      associations between diet, menopause, and health and consideration of the role of
      dietary factors in explaining health-related differences among women of diverse
      ethnicity.

PMID- 12218720
TI  - Effects of raloxifene on bone density, biomarkers, and histomorphometric and
      biomechanical measures in ovariectomized cynomolgus monkeys.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of raloxifene on
      bone density, strength, metabolism, and histomorphometric characteristics in
      ovariectomized cynomolgus monkeys. DESIGN: A prospective, longitudinal study was
      designed to examine the effects of conjugated equine estrogens (0.04 mg/kg, CEE)
      and raloxifene (1 or 5 mg/kg, R1 and R5, respectively) on bone density,
      biomarkers, histomorphometry, and strength. Control groups included
      ovariectomized and sham-operated monkeys. Treatment was initiated the day after
      ovariectomy and continued for 24 months. Bone biomarker data were collected at
      baseline and every 3 months after surgery. Bone mass was determined at baseline
      and every 6 months after ovariectomy. Iliac biopsies were collected at baseline
      and 16 months postovariectomy, and the second lumbar vertebra and left midshaft
      femur collected at necropsy were examined histomorphometrically. Bone
      biomechanical properties were determined for the right femur and vertebrae.
      RESULTS: Compared with the placebo-treated ovariectomized monkeys, the high-dose
      raloxifene group had lower levels of alkaline phosphatase, tartrate-resistant
      acid phosphatase, urinary CrossLaps (collagen degradation products), and greater
      bone mass in the lumbar vertebrae. In the endocortical compartment, the high-dose
      raloxifene group had significantly lower mineralizing surface, mineral apposition
      rate, and bone formation rate in the iliac biopsy collected at 16 months and
      lower bone formation rate in the second lumbar vertebra. Within the midshaft
      femur, low-dose raloxifene significantly decreased the osteonal and total bone
      formation rates and also prevented the decrease in Young's modulus induced by
      ovariectomy in the midshaft femur. CONCLUSIONS: High-dose raloxifene prevented
      the development of osteopenia in the ovariectomized monkey by reducing bone
      turnover, albeit to a lesser extent than CEE. Histomorphometric and biomarker
      data suggest that mechanisms underlying the effect of raloxifene differ somewhat
      from that of CEE.

PMID- 12218721
TI  - Effects of a standardized soy extract on hot flushes: a multicenter, double
      blind, randomized, placebo-controlled study.
AB  - OBJECTIVE: To investigate the effect of an oral soy isoflavone extract
      (Phytosoya) on hot flushes in menopausal women. DESIGN: The study was conducted
      on outpatients according to a multicenter, randomized, double-blind, placebo
      controlled, parallel-group design. A total of 75 patients in natural or surgical
      menopause suffering from at least seven hot flushes per day were randomized to
      receive during 4 months either soy isoflavone extract (total of 70 mg genistin
      and daidzin per day) or placebo. RESULTS: There is evidence to suggest that 16
      weeks of treatment with soy extract can help reduce the mean number of hot
      flushes per 24 hours in menopausal women. Withdrawals during this trial made it
      difficult to obtain an unbiased estimate of the true treatment effect, but
      numerous sensitivity analyses lend support to the suggestion that taking soy
      extract can be beneficial in the treatment of hot flushes. In particular, women
      taking soy extract had a 38% reduction in the mean number of hot flushes by week
      4 and a 51% reduction by week 8. By the end of week 16, patients taking soy
      extract had a 61% reduction in their daily hot flushes versus a 21% reduction
      obtained with the placebo. "Responders" (defined as patients whose hot flushes
      were reduced by at least 50% at the end of treatment period) were 65.8% in the
      soy extract group and 34.2% in the placebo group ( < 0.005). CONCLUSION: Soy
      isoflavone extract may help to reduce the frequency of hot flushes in climacteric
      women and provides an attractive addition to the choices available for relief of
      hot flushes.

PMID- 12218722
TI  - Changes in lipid and lipoprotein profile in postmenopausal women receiving low
      dose combinations of 17beta-estradiol and norethisterone acetate.
AB  - OBJECTIVE: To evaluate the modification of lipid and lipoprotein by use of low
      doses of continuous-combined formulations of 17beta-estradiol (E ) and
      norethisterone acetate (NETA) in healthy postmenopausal women. DESIGN: The study
      was designed as a double-blind, randomized, placebo-controlled trial. A total of
      120 healthy postmenopausal women were randomized to one of three treatment arms:
      (1) placebo group ( = 40); (2) E /NETA 0.25-mg group-subjects receiving oral
      continuous-combined E 1 mg and NETA 0.25 mg ( = 40); (3) E /NETA 0.5-mg group
      women who were treated with E 1 mg and NETA 0.5 mg ( = 40). The duration of study
      was 12 months. Plasma levels of total cholesterol, low-density lipoprotein (LDL),
      high-density lipoprotein (HDL), and very low-density lipoprotein (VLDL)
      cholesterol, triglycerides, lipoprotein(a), apolipoprotein A and apolipoprotein B
      were determined on four occasions (i.e., baseline, 3-, 6-, and 12-month visits).
      RESULTS: There were no differences in the baseline characteristics among the
      three groups. A total of 102 women completed the study, resulting in a compliance
      rate of 85%. There was a significant reduction of total cholesterol, LDL
      cholesterol, and lipoprotein(a) in both combined groups when compared with
      placebo. The level of apolipoprotein B declined significantly only in the E /NETA
      0.25-mg group. Decrements were observed within 3 months of treatment and
      maintained thereafter. No significant changes were found in triglycerides, VLDL
      cholesterol, HDL cholesterol, apolipoprotein A, and LDL/HDL ratio. Between the
      two active combined groups, no statistically significant differences were noted.
      CONCLUSION: Favorable changes in lipids and lipoproteins were associated with the
      low dose of E /NETA combinations. These effects may contribute to the reduction
      or prevention of atherogenesis in postmenopausal women.

PMID- 12218723
TI  - Effectiveness of Alora estradiol matrix transdermal delivery system in improving
      lumbar bone mineral density in healthy, postmenopausal women.
AB  - OBJECTIVE: To determine the lowest effective dose of an estradiol (E ) matrix
      type transdermal delivery system (EMTDS; Alora) for preventing bone loss in
      postmenopausal women. DESIGN: This double-blind, double-dummy, randomized,
      placebo-controlled, multicenter study enrolled 355 nonosteoporotic postmenopausal
      women who had been hysterectomized with or without oophorectomy at least 12
      months earlier. Participants were randomly assigned to one of three doses of the
      EMTDS (0.025, 0.05, or 0.075 mg/day) or placebo administered twice weekly. Lumbar
      bone mineral density (LBMD) was measured by dual-energy x-ray absorptiometry at
      screening and after 1 and 2 years of treatment. Safety was assessed at regularly
      scheduled visits. RESULTS: EMTDS provided statistically significant and
      clinically meaningful changes in LBMD relative to placebo. At 2 years, LBMD
      declined from baseline by 0.59% in the placebo group, but it increased from
      baseline by 1.65% ( = 0.0065), 4.08% ( = 0.0001), and 4.82% ( = 0.0001) in the
      EMTDS 0.025, 0.05, and 0.075 mg/day groups, respectively. The corresponding
      responder rates (defined as no change or increase in LBMD at endpoint) were 39.7%
      for placebo, 59.6%, 79.3%, and 83.9% in the EMTDS 0.025, 0.05, and 0.075 mg/day
      groups, respectively. Mean serum E concentrations were proportional to the dose
      of the E transdermal system and did not accumulate over the course of the study.
      Adverse events were generally comparable across treatment groups, with the
      majority being mild or moderate in severity and unrelated to study medication.
      Mammogram findings and other safety assessments were also comparable across
      groups and did not reveal any safety concerns with 2-y transdermal E treatment.
      CONCLUSIONS: The EMTDS (Alora) administered twice weekly improves lumbar bone
      mineral density in healthy postmenopausal women, with the benefit of treatment
      evident by 1 year. The lowest effective dose is 0.025 mg/day.

PMID- 12218724
TI  - Gynecologists' trends and attitudes toward prescribing hormone replacement
      therapy during menopause.
AB  - OBJECTIVE: To examine the attitudes and prescription practices of gynecologists
      in the United States and Israel with regard to hormone replacement therapy (HRT)
      for postmenopausal women. The current recommendations for the use of HRT for
      menopausal symptoms were reviewed. DESIGN: An eight-item questionnaire was sent
      by electronic mail or posted to randomly selected members of The North American
      Menopause Society ( = 250) and the Israeli Menopausal Society ( = 250), all of
      whom were physician gynecologists. RESULTS: Eighty-seven percent of the
      questionnaires ( = 435) were completed and were eligible for analysis. Results
      showed that 400 physicians (92%) routinely offered HRT to their menopausal
      patients. For women with an intact uterus, 72.5% preferred to use a continuous
      estrogen-progesterone regimen, and 27.5% preferred to use a sequential combined
      regimen. The treatment was prescribed for 10 years or more by 86.4% of the
      American gynecologists, compared with only 66.3% of the Israeli gynecologists ( =
      0.001). Overall, the majority of physicians recommended alendronate for
      recalcitrant osteoporosis and dietary supplements for all women. However,
      significant differences were found between the American and Israeli groups: 71%
      of the Americans versus 55.6% of the Israelis prescribed alendronate ( = 0.02);
      97.8% versus 71.33% recommended calcium and vitamin D; and 51.6% versus 38.8%
      recommended multivitamins ( = 0.001 for both groups). Phytoestrogens, alone or in
      combination with HRT, were recommended by 57.5% ( = NS between groups), and
      antidepressive drugs were prescribed by only 11% (15.1% of the Americans and 6.3%
      of the Israelis; = 0.001). CONCLUSION: Most gynecologists recommend HRT during
      menopause. For women with an intact uterus, the preferred regimen was continuous
      combined HRT with estrogen and progesterone. The treatment duration is subject to
      wide variations, from no time limit to discontinuation after 5 to 10 years.
      Dietary supplements as well as alendronate, alone or in combination with HRT, are
      popular for severe osteoporosis. We suggest that, until definitive guidelines
      become available, an individualized approach should be applied, with careful
      consideration of both the benefits and risks of treatment.

PMID- 12218725
TI  - Combination therapy of low-dose medroxyprogesterone acetate and oral estrogen
      does not affect endothelial function in the forearms of postmenopausal women.
AB  - OBJECTIVE: We investigated whether low-dose medroxyprogesterone acetate (MPA)
      combined with oral estrogen had adverse effects on endothelial function compared
      with oral estrogen alone in postmenopausal women with mild hypercholesterolemia.
      DESIGN: Subjects were divided into two groups. One group received conjugated
      equine estrogen (CEE, 0.625 mg daily) orally for the first 3 months, followed by
      estrogen combined with MPA (2.5 mg daily) orally for an additional 3 months ( =
      26). The other group received no treatment (control group, = 12). Forearm blood
      flow (FBF) during reactive hyperemia and after sublingual nitroglycerin
      administration was measured by strain-gauge plethysmography. Nitrite/nitrate,
      angiotensin-converting enzyme, and lipid concentrations were measured in the
      serum. RESULTS: Both CEE and CEE combined with MPA significantly increased the
      FBF during reactive hyperemia. This increase was similar in both active treatment
      phases. No changes were seen in controls. FBF after sublingual nitroglycerin did
      not change over 6 months in either group. Significant and similar increases in
      serum concentration of nitrite/nitrate and plasma renin activity as well as
      decreases in angiotensin-converting enzyme activity were found in both treatment
      phases. No such changes occurred in the control group. There was no significant
      increase in high-density lipoprotein cholesterol or decrease in low-density
      lipoprotein cholesterol between the treatment phases. Likewise, no such changes
      were observed in the control group. CONCLUSIONS: Our 6-month study suggests that
      the addition of low-dose MPA with CEE had no adverse effects on forearm
      resistance artery endothelial function compared with CEE alone.

PMID- 12218726
TI  - Measurement of hot flashes by sternal skin conductance and subjective hot flash
      report in Puebla, Mexico.
AB  - OBJECTIVE: To measure hot flashes by sternal skin conductance in an urban Mexican
      population and to determine variables associated with hot flash reporting and
      measurement. DESIGN: From June 1999 to August 2000, 67 perimenopausal women aged
      40 to 65 years participated in interviews, anthropometric measures, and a 2-h
      recording of sternal skin conductance. Changes in sweating were used to
      demonstrate the presence/absence of a hot flash. During the test, women were
      asked to report if they experienced a hot flash. RESULTS: During the study
      period, 10 women reported and demonstrated every hot flash, 24 women never
      reported or demonstrated a hot flash, 7 demonstrated hot flashes but did not
      report any of them, 7 reported hot flashes but did not demonstrate any of them,
      and 19 showed a mixture of responses. Women who demonstrated hot flashes by
      sternal skin conductance were measured in a warmer room, had more years of
      education, consumed more eggs as a child, recalled a heavier weight at age 18,
      and had a lower body mass index at interview compared with women who did not
      demonstrate hot flashes by sternal skin conductance. Women who subjectively
      reported hot flashes were measured in a warmer room, were more likely to be
      postmenopausal, reported more frequent consumption of coffee, and spent fewer
      months breast-feeding their last child compared with women who did not report the
      experience of hot flashes during the testing period. CONCLUSION: Room temperature
      explained part of the variation between women who did and did not demonstrate hot
      flashes via sternal skin conductance, between women who did and did not report
      the experience of hot flashes, and between women who did and did not demonstrate
      concordance in objective and subjective measures. In addition to room
      temperature, coffee intake, months spent breast-feeding the last child, and
      recalled weight at age 18 were important variables predicting hot flash
      experience.

PMID- 12218727
TI  - Use of hormone replacement therapy among Chilean women: a comparison between
      socioeconomic levels.
AB  - OBJECTIVE: To compare the use of hormone replacement therapy (HRT) among Chilean
      women according to their socioeconomic level. METHODS: A total of 540 women
      between 50 and 79 years of age were interviewed in Santiago, Chile. Women were
      allocated into two groups (H, high; L, low), according to their socioeconomic
      status. RESULTS: Each group consisted of 270 women. The mean age and percentage
      of menopausal women were similar in both groups. Of the interviewed women, 47%
      had taken HRT at some time; marked differences between the two groups were
      observed (L, 15%; H, 79%; < 0.0001). In group H, the percentage of women who had
      been advised about HRT was close to 88%, whereas, in group L, the percentage was
      only 24%. Among the women who were informed about HRT, 83% ( = 253) had used it
      at some time. The percentage of women who used HRT for >2 years was similar in
      both groups. The main reason for not taking HRT in group H was fear of adverse
      effects, whereas the main reason for not taking it in group L was the lack of
      medical advice. CONCLUSIONS: The percentage of women in the low socioeconomic
      group who use HRT is low. Medical advice is fundamental to increasing HRT use in
      this group.

PMID- 12218728
TI  - Controversy about uterine effects and safety of SERMs: the saga continues.
AB  - From the perspective of endometrial safety, there has been great controversy
      about what special management, if any, tamoxifen-treated patients should undergo.
      Periodic blind endometrial sampling or transvaginal ultrasound has been advocated
      by some. Because of the problems associated with either of these techniques
      alone, we recommended an approach that used transvaginal ultrasound and then
      proceeded to sonohysterography when the endometrial echo on transvaginal
      ultrasound was not reliably thin and distinct. The American College of
      Obstetricians and Gynecologists (ACOG), in its committee opinion, stated that
      patients receiving tamoxifen therapy should only have an annual pelvic exam with
      pap smear if they remain asymptomatic. Newer data suggest, however, that there
      are high- and low-risk groups that can be identified by pretreatment screening.
      Before tamoxifen therapy, 17% of patients have polyps. These patients have 17
      times the incidence of atypical hyperplasia than those whose uterus was negative
      before tamoxifen therapy. Such findings call into question the validity of the
      only study of raloxifene where uterine safety was the primary endpoint. In that
      study, any woman with baseline endometrial findings other than pristinely
      negative (i.e., low risk) was excluded. However, other raloxifene studies without
      pretreatment screening show relative risk (RR) = 0.8 (95% CI = 0.2, 2.7) for
      endometrial carcinoma. This compares with the women over 50 years of age in the
      Breast Cancer Prevention Trial (National Surgical Adjuvant Breast and Bowel
      Project P-1) with tamoxifen when the RR = 4.01 (95% CI= 1.70, 10.90). The
      existence of potentially high- and low-risk groups should be taken into account
      in any future clinical trials looking at the endometrial safety of selective
      estrogen receptor modulators (SERMs).

PMID- 12218729
TI  - Letter to the editor.

PMID- 12218730
TI  - Hypokinetic circulation in persons with paraplegia.
AB  - INTRODUCTION: It is well established that hemodynamic dysfunction, resulting in
      diminished upper-extremity work capacity, occurs in persons with spinal cord
      injury (SCI) as compared with those who are nondisabled (ND). Although it has
      been shown that persons with paraplegia display higher values of heart rate (HR)
      with lower values of stroke volume (SV) during exercise, it is not resolved
      whether there is adequate compensation to produce similar values of cardiac
      output (.Q) as in ND. PURPOSE: This study examined central cardiovascular
      responses (HR, SV, and .Q) of 20 subjects with complete thoracic level SCI (T(4)
      T(11)) and 20 sedentary ND subjects during matched levels of arm-crank (AC)
      exercise. METHODS: All subjects performed an incremental peak AC test to
      volitional exhaustion with continuous metabolic analysis and HR measurement via
      open circuit spirometry and 12-lead electrocardiography, respectively. Stroke
      volume was assessed using transthoracic impedance. RESULTS: Heart rate was higher
      for SCI (P< 0.05) with significantly lower values for SV and .Q at rest
      (approximately 25%). Peak responses were significantly higher for ND in all
      factors except HR. Although subpeak HRs at matched absolute workloads were
      significantly higher for SCI (12-20 beats.min (-1) ), SV and .Q were
      significantly lower (P< 0.05). CONCLUSIONS: The results of this study indicate
      that .Q is significantly lower in SCI than in ND during AC, despite significantly
      greater values of HR. These findings also suggest that the disparity in exercise
      values of .Q is related to differences exhibited at rest.

PMID- 12218731
TI  - Landing adaptations after ACL reconstruction.
AB  - PURPOSE: The purpose of this study was to determine whether fully rehabilitated
      ACL reconstructed (ACLr) recreational athletes utilize adapted lower-extremity
      joint kinematics and kinetics during a high-demand functional task. METHODS: The
      kinematic and kinetic performance of 11 healthy and 11 hamstring ACLr
      recreational athletes were compared during a 60-cm vertical drop landing.
      RESULTS: At initial ground contact, the ACLr group demonstrated greater hip
      extension and ankle plantarflexion compared with the healthy group. The peak
      vertical ground-reaction force was not different between groups, but the ACLr
      group delayed the time to its occurrence. The knee extensors provided the major
      energy absorption function for both groups; however, the ACLr group performed 37%
      more ankle plantarflexor work and 39% less hip extensor work compared with the
      healthy group. CONCLUSIONS: The hamstring ACLr recreational athletes utilized an
      adapted landing strategy that employed the hip extensor muscles less and the
      ankle plantarflexor muscles more. The harvesting of the medial hamstring muscles
      for ACL reconstruction may contribute to the utilization of this protective
      landing strategy.

PMID- 12218732
TI  - Possible mechanism of quadriceps femoris weakness in patients with ruptured
      anterior cruciate ligament.
AB  - PURPOSE: The purpose of this study was to test the hypothesis that loss of
      afferent feedback due to rupture of anterior cruciate ligament (ACL) is the cause
      of quadriceps femoris (QF) weakness through gamma loop. Two experiments were
      designed to prove our hypothesis. METHODS: In experiment 1, the maximal voluntary
      contraction (MVC) of knee extension and integrated electromyogram (I-EMG) of
      vastus medialis (VM), vastus lateralis (VL), and rectus femoris (RF) were
      measured in 13 patients with ruptured ACL and 7 healthy volunteers before and
      after injection of anesthetic agent into the knee. In experiment 2, MVC of knee
      extension and I-EMG of the VM, VL, and RF were measured in 13 patients with
      ruptured ACL, 7 knee-anesthetized healthy subjects, and 12 normal subjects,
      before and after 20-min vibration stimulation applied to the infrapatellar
      tendon. RESULTS: The results of experiment 1 revealed that injection of
      anesthetic agent into the knee capsule resulted in significant decrease of MVC
      and I-EMGs. In experiment 2, the mean percentage change of MVC in the control
      group was significantly lower than that in the other two groups. There was no
      significant difference between knee-anesthetized group and patients with ruptured
      ACL. The mean percentage change of I-EMG showed a pattern similar to that of MVC.
      CONCLUSION: Our results suggest that loss of feedback from mechanoreceptors in
      ACL is the underlying mechanism of weakness of QF in patients with ACL lesion.
      This conclusion is based on chronic suppression of recruitment of high-threshold
      motor units during voluntary contraction because ACL lesion leads to chronic
      reduction in Ia-feedback to muscles around the knee due to a lack of feedback
      from ACL to gamma motor neurons.

PMID- 12218733
TI  - Relationships between HR and (.)VO(2) in the obese.
AB  - PURPOSE: To enable more targeted exercise prescription for the obese, the purpose
      of this study was to consider relationships between relative indices of
      (.)VO(2peak), (.)VO(2)R, HR(peak), and HRR in a sample of obese adults. In
      particular, the study aimed to determine whether %HRR was equivalent to
      %(.)VO(2peak) or %(.)VO(2)R. A further aim was to evaluate whether the
      %(.)VO(2peak)-%HR(peak) relationship defined by the ACSM holds in the obese
      population, or whether there is a deviation in this relationship as is noted in
      individuals with low functional capacity. Finally, the study aimed to determine
      the degree of variability in relative workload relating to lactate threshold
      (LT). METHODS: Thirty-two sedentary obese adults, 17 women and 15 men (42.1 +/-
      9.6 yr; 37.4 +/- 5.7 kg.m) attended a testing session each week for 3 wk. The
      three sessions involved 1) familiarization with testing protocols; 2) graded
      treadmill tests to evaluate submaximal and peak cardiorespiratory capacity; and
      3) assessment of body composition via deuterium dilution, and resting HR
      (HR(rest)) and oxygen consumption ((.)VO(2rest)) collected during assessment of
      resting metabolic rate (RMR) via a ventilated hood system. RESULTS: The primary
      findings were that in the obese: 1) the %HR(peak)-%(.)VO(2peak) relationship was
      significantly greater than the ACSM recommendations, 2) the %HRR was equivalent
      with (.)VO(2)R not %(.)VO(2peak), and 3) exercise prescription at fixed
      percentages of (.)VO(2peak) or HR(peak) corresponded with wide ranges of exercise
      intensities in relation to LT. CONCLUSIONS: The relationships between
      cardiorespiratory parameters defined in normal weight populations differ to some
      degree in the obese, and this has implications both for optimizing exercise
      intensity for weight loss and exercise adherence in obese adults.

PMID- 12218734
TI  - Relations of adiposity and effects of training on the left ventricle in obese
      youths.
AB  - PURPOSE: 1) To determine the relations of left ventricular (LV) structure and
      function to total body composition, visceral adipose tissue (VAT), and
      hemodynamics in obese children; 2) to determine the effects of 4-month of
      physical training (PT) on LV structure and function and hemodynamics; and 3) to
      explore determinants of individual variability in response to PT. METHODS:
      Measurements included LV structure/function with echocardiography, total body
      composition with dual-energy x-ray absorptiometry, VAT with magnetic resonance
      imaging (MRI), and resting and exercising hemodynamics with a Dinamap monitor and
      Doppler-echocardiography. Youths were randomly assigned to engage in PT for the
      first or second 4-month periods of the 8-month intervention period. RESULTS:
      Correlation and regression at baseline showed that elevated LV mass was
      associated with excess general and visceral adiposity, and elevated cardiac
      output. Although the PT had favorable effects on percent body fat and VAT, no
      significant changes were found in LV or hemodynamic variables. Over the 4-month
      period of the PT intervention, those who increased the most in VAT tended to
      increase the most in LV mass. CONCLUSION: General and visceral adiposity were
      associated with elevated LV mass. However, no evidence was provided that 4 months
      of PT had a significant effect on LV or hemodynamic variables.

PMID- 12218735
TI  - Nandrolone excretion is not increased by exhaustive exercise in trained athletes.
AB  - PURPOSE: The anabolic steroid nandrolone is widely used as a performance
      enhancer. Traces of its naturally occurring metabolite 19-norandrosterone (19-NA)
      have been found in human urine (below 0.6 ng.mL(-1)), and it has been suggested
      that strenuous exercise may increase urinary 19-NA. The aim of our study was to
      assess the effect of exhaustive exercise on the nandrolone excretion under
      controlled conditions in two groups of trained male athletes, one composed of
      judoka and the other of long-distance runners. METHODS: A Wingate test and a
      treadmill limited-time test (running at 85% (.)VO(2max)) were carried out on 14
      judoka and 15 athletes. Hydration was controlled during each session. Urine
      samples were obtained before each test and 30 min, 60 min, and 24 h after each
      test. Urinary 19-NA concentrations were determined using gas chromatography
      coupled with mass spectrometry. RESULTS: Baseline urinary 19-NA concentrations
      varied widely across individuals, from undetectable levels to 0.250 ng.mL (
      1)(mean, 0.048 +/- 0.050 ng.mL(-1)). The both exercise tests did not
      significantly modified urinary 19-NA levels in the two groups of subjects.
      CONCLUSION: Our study provides compelling evidence that endogenous nandrolone
      production in male athletes, during two very different types of exercise,
      produces urine levels far below the IOC threshold of 2 ng.mL(-1) urine. Thus,
      exercise does not induce endogenous nandrolone secretion.

PMID- 12218736
TI  - Effects of topical analgesics on the pressor response evoked by muscle afferents.
AB  - PURPOSE: Pressor responses are reflexly evoked by the activation of groups III
      and IV muscle afferents, which are also known to mediate nociceptive responses.
      In this experiment, the effects of analgesic balm (AB) application on these
      responses were investigated without the interference of other types of anesthesia
      or effects from the higher brain. METHODS: Heart rate (HR), blood pressure, and
      end-tidal CO(2) were monitored in midcollicularly decerebrated cats. Static
      contractions (30 s) of hindlimb muscles were evoked by electric stimulation of L7
      and S1 ventral roots. After control runs, a commercial AB (1% capsaicin, 12.5%
      methyl salicylate) was applied to the skin surface over the contracting muscles.
      Muscle contractions were evoked every 10 min, alternating between the two
      hindlimbs. RESULTS: Changes in mean arterial pressure (MAP) evoked by static
      ipsilateral muscular contraction were significantly attenuated 20 min and 40 min
      after AB application. The decreases in the pressor response were significant at
      both the initial and the last parts of the stimulus intervention after 20 min of
      AB application. There were no significant changes in the response to contraction
      of the hindlimb contralateral to the AB application. Application of AB to the
      contralateral leg did not add to the ipsilateral effects. CONCLUSIONS: AB
      application to the skin surface over contracting muscles significantly decreased
      autonomic responses to static muscular contraction. This effect was independent
      of higher cortical processing and strongly suggests that application of methyl
      salicylate and capsaicin on the skin has analgesic effects on signals from
      receptors located in muscle.

PMID- 12218737
TI  - Lower-body negative-pressure exercise and bed-rest-mediated orthostatic
      intolerance.
AB  - PURPOSE: Supine, moderate exercise is ineffective in maintaining orthostatic
      tolerance after bed rest (BR). Our purpose was to test the hypothesis that adding
      an orthostatic stress during exercise would maintain orthostatic function after
      BR. METHODS: Seven healthy men completed duplicate 15-d 6 degrees head-down tilt
      BR using a crossover design. During one BR, subjects did not exercise (CON).
      During another BR, subjects exercised for 40 min.d(-1) on a supine treadmill
      against 50-60 mm Hg LBNP (EX). Exercise training consisted of an interval
      exercise protocol of 2- to 3-min intervals alternating between 41 and 65%
      (.)VO(2max). Before and after BR, an LBNP tolerance test was performed in which
      the LBNP chamber was decompressed in 10-mm Hg stages every 3 min until
      presyncope. RESULTS: LBNP tolerance, as assessed by the cumulative stress index
      (CSI) decreased after BR in both the CON (830 +/- 144, pre-BR vs 524 +/- 56 mm
      Hg.min, post-BR) and the EX (949 +/- 118 pre-BR vs 560 +/- 44 mm Hg.min, post-BR)
      conditions. However, subtolerance (0 to -50 mm Hg LBNP) heart rates were lower
      and systolic blood pressures were better maintained after BR in the EX condition
      compared with CON. CONCLUSION: Moderate exercise performed against LBNP
      simulating an upright 1-g environment failed to protect orthostatic tolerance
      after 15 d of BR.

PMID- 12218738
TI  - Perceptual versus physiological heat strain during exercise-heat stress.
AB  - PURPOSE: The physiological strain index (PSI) has been proposed as a universally
      applicable measure of exercise-heat strain. Unknown is whether this index, based
      on normalized increases in core temperature and heart rate, is matched by its
      perceptual analog. METHODS: By using a similar mathematical construct to the PSI,
      the perceptions of thermal sensation and perceived exertion were combined, and
      the resultant index, PeSI, was compared with its physiological counterpart,
      denoted as PhSI, for the exercise-heat stress specific to this study. Twenty-six
      young and healthy subjects wore semi-impermeable clothing and walked (3.5 km.h(
      1)) under hot conditions (40 degrees C and 30% RH) until exhaustion or when their
      core temperature reached 39.5 degrees C. Subjects were divided into two fitness
      groups [endurance trained (T) and untrained (U)] comprised of 10 men and 3 women
      each. U subjects had a higher level of body fatness (mean +/- SD 18.1 +/- 5.3 vs
      12.6 +/- 4.5%; P=0.010) and a lower level of aerobic fitness ((.)VO(2max)= 43.6
      +/- 3.8 +/- vs 59.0 +/- 6.2 mL.min(-1).kg(-1); P<0.001). RESULTS: During the
      first hour of exposure, there was no group difference in PhSI, yet T perceived
      their physiological strain (PeSI) lower than U (P=0.002). Further, the indices
      were not different for U whereas PhSI was higher than PeSI for T (P=0.008). At
      the end of the exposure, T had a higher value of PhSI than U (8.23 +/- 0.72 vs
      6.74 +/- 1.47; = 0.002), but there was no group difference in PeSI. Although the
      indices were again not different for U, PhSI at the end was higher than PeSI for
      T (6.14 +/- 1.68; P<0.001). CONCLUSION: T underestimated and U consistently
      perceived their physiological strain, as defined by PhSI, in accordance with the
      measured increases in core temperature and heart rate throughout an exposure to
      uncompensable exercise-heat stress.

PMID- 12218739
TI  - Reliability and validity of Canada's Physical Activity Monitor for assessing
      trends.
AB  - PURPOSE: This investigation assessed the reliability and criterion validity of
      the Physical Activity Monitor, a telephone-interview adaptation of the Minnesota
      Leisure Time Physical Activity Questionnaire (MLTPAQ), which is currently used to
      assess trends in the Canadian population. METHODS: A sample of 512 people aged 18
      yr and older was selected by random-digit dialing for telephone interviewing in
      the reliability study. The Monitor questions were administered twice, 3 wk apart.
      For the criterion validity study, a sample of 148 people aged 18-69 yr was
      selected at random from households. Participants completed the Monitor questions
      by telephone and an in-home step test to estimate maximum oxygen uptake. Another
      random sample of individuals aged 18-69 yr participated in a comparison study of
      the Monitor against the 1988 Campbell's Survey of Well-Being (CSWB) instrument.
      All studies were conducted in the vicinity of Toronto, Ontario. Spearman
      correlations controlling for age and sex were calculated as a measure of
      association for the reliability, validity, and comparison studies. Validity
      estimates were further adjusted for body mass index and physical activity demands
      of work and chores. RESULTS: The Monitor instrument produced reliable estimates
      of total energy expenditure (P=0.90, P<0.0001) with criterion validity of 0.36
      (P<0.0001). The association between estimates of total energy expenditure derived
      from the Monitor and CSWB instruments was 0.77 (P<0.0001). CONCLUSION: The
      Physical Activity Monitor has acceptable test-retest reliability and criterion
      validity. The research also demonstrated that for the purpose of population
      monitoring a change in data collection mode-telephone interview versus self
      administration in households-can yield reasonably comparable estimates from two
      adaptations of the MLTPAQ.

PMID- 12218741
TI  - Symposium: Limits to fat oxidation by skeletal muscle during exercise-
      introduction.
AB  - Lipids, in the form of adipose tissue triacylglycerol (TG), intramuscular
      triglyceride (IMTG), and dietary-derived fatty acids (FA) from plasma TG
      (chylomicrons), and very low-density lipoproteins (VLDL), represent the largest
      store of nutrient energy in humans. Yet despite the abundance of endogenous TG,
      there is limited capacity for FA oxidation during exercise: there are no
      mechanisms that match the availability and metabolism of FA to the rate of energy
      expenditure. Because of the body's limited carbohydrate (CHO) stores, and because
      depletion of muscle and liver glycogen reserves often coincide with exhaustion,
      there is interest in several nutritional interventions that increase FA
      availability and rates of fat oxidation during exercise: such strategies have the
      potential to slow the rate of glycogen utilization and delay the onset of
      fatigue. The five papers comprising this symposium provide a synopsis of 1) the
      regulation of fat oxidation in human skeletal muscle during aerobic exercise; 2)
      selected nutritional techniques that increase fat oxidation, spare endogenous CHO
      stores, and modify exercise capacity; and 3) dietary manipulations that alter
      macronutrient availability and muscle gene expression.

PMID- 12218740
TI  - Accumulating brisk walking for fitness, cardiovascular risk, and psychological
      health.
AB  - PURPOSE: To compare the effects of different patterns of regular brisk walking on
      fitness, risk factors for cardiovascular disease, and psychological well-being in
      previously sedentary adults. METHODS: Twenty-one subjects (14 women), aged 44.5
      +/- 6.1 yr (mean +/- SD) were randomly assigned to two different, 6-wk programs
      of brisk walking in a cross-over design, with an interval of 2 wk. One program
      comprised one 30-min walk per day, 5 d.wk(-1) (long bout) and the other three 10
      min walks per day, also 5 d.wk(-1) (short bouts). All walking was at 70-80% of
      predicted maximal heart rate. Maximal oxygen uptake ((.)VO(2max)), body
      composition, resting arterial blood pressure, fasting plasma lipoprotein
      variables, and psychological parameters were assessed before and after each
      program. RESULTS: Overall, subjects completed 88.2 +/- 1.1% and 91.3 +/- 4.1% of
      prescribed total walking time in the short- and long-bout programs, respectively.
      Both programs increased plasma concentrations of high-density lipoprotein
      cholesterol, and decreased concentrations of triacylglycerol and total
      cholesterol (all < 0.05). There were no changes in body mass, but the sum of four
      skinfolds, waist circumference, and hip circumference were decreased after both
      walking programs (all P<0.05). Predicted (.)VO(2max) increased with both programs
      ( P<0.05), but this increase was greater with the program based on short bouts
      (P<0.05). Both walking patterns resulted in similar decreases in tension/anxiety
      (P<0.05). CONCLUSION: These findings suggest that three short bouts (10 min) of
      brisk walking accumulated throughout the day are at least as effective as one
      continuous bout of equal total duration in reducing cardiovascular risk and
      improving aspects of mood in previously sedentary individuals.

PMID- 12218742
TI  - Regulation of skeletal muscle fat oxidation during exercise in humans.
AB  - Fat and carbohydrate are the major energy substrates during aerobic exercise in
      well-fed humans. The regulation of fat metabolism during exercise has not been as
      thoroughly studied as carbohydrate metabolism, especially in human skeletal
      muscle. Traditionally, it was believed that the regulation of skeletal muscle fat
      metabolism was mainly at the level of the delivery of free fatty acids to the
      muscle (adipose tissue lipolysis) and transport of the long chain fatty acids
      into the mitochondria. It is now known that the transport of fatty acids into the
      muscle cell and the regulation of muscle triacylglycerol lipase activity are also
      important sites of regulation. New lines of research are currently underway
      examining the regulation of fat metabolism in skeletal muscle at the level of fat
      transport across the sarcolemmal and mitochondrial membranes and regulation of TG
      lipase activity in both rodent and human models. A major goal of this research is
      to determine the regulatory signals that control the up-regulation of fat
      metabolism during the transition from rest to low and moderate aerobic exercise
      (30-65% (.)VO(2max)) and the down-regulation that occurs when exercising at
      intense aerobic exercise (approximately 85% (.)VO(2max)). Although it is expected
      that the signals that activate carbohydrate metabolism during exercise (Ca and
      free ADP, AMP, and P(i)) would also play a role in fat metabolism, this has not
      been demonstrated to date.

PMID- 12218743
TI  - Effect of increased fat availability on metabolism and exercise capacity.
AB  - Several procedures have been utilized to elevate plasma free fatty acid (FFA)
      concentration and increase fatty acid (FA) delivery to skeletal muscle during
      exercise. These include fasting, caffeine ingestion, L-carnitine supplementation,
      ingestion of medium-chain and long-chain triglyceride (LCT) solutions, and
      intravenous infusion of intralipid emulsions. Studies in which both untrained and
      well-trained subjects have ingested LCT solutions or received an infusion of
      intralipid (in combination with an injection of heparin) before exercise have
      reported significant reductions in whole-body carbohydrate oxidation and
      decreased muscle glycogen utilization during both moderate and intense dynamic
      exercise lasting 15-60 min. The effects of increased FA provision on rates of
      muscle glucose uptake during exercise are, however, equivocal. Despite
      substantial muscle glycogen sparing (15-48% compared with control), exercise
      capacity is not systematically improved in the face of increased FA availability.

PMID- 12218744
TI  - Effects of short-term fat adaptation on metabolism and performance of prolonged
      exercise.
AB  - The concept of manipulating an individuals habitual diet before an exercise bout
      in an attempt to modify patterns of fuel substrate utilization and enhance
      subsequent exercise capacity is not new. Modern studies have focused on
      nutritional and training strategies aimed to optimize endogenous carbohydrate
      (CHO) stores while simultaneously maximizing the capacity for fat oxidation
      during continuous, submaximal (60-70% of maximal O(2) uptake [(.)VO(2max)]
      exercise. Such "nutritional periodization" typically encompasses 5-6 d of a high
      fat diet (60-70% E) followed by 1-2 d of high-CHO intake (70-80% E; CHO
      restoration). Despite the brevity of the adaptation period, ingestion of a high
      fat diet by endurance-trained athletes results in substantially higher rates of
      fat oxidation and concomitant muscle glycogen sparing during submaximal exercise
      compared with an isoenergetic high-CHO diet. Higher rates of fat oxidation during
      exercise persist even under conditions in which CHO availability is increased,
      either by having athletes consume a high-CHO meal before exercise and/or ingest
      glucose solutions during exercise. Yet, despite marked changes in the patterns of
      fuel utilization that favor fat oxidation, fat-adaptation/CHO restoration
      strategies do not provide clear benefits to the performance of prolonged
      endurance exercise.

PMID- 12218745
TI  - Long-term fat diet adaptation effects on performance, training capacity, and fat
      utilization.
AB  - It is well known that adaptation to a fat-rich carbohydrate-poor diet results in
      lower resting muscle glycogen content and a higher rate of fat oxidation during
      exercise when compared with a carbohydrate-rich diet. The net effect of such an
      adaptation could potentially be a sparing of muscle glycogen, and because muscle
      glycogen storage is coupled to endurance performance, it is possible that
      adaptation to a high-fat diet potentially could enhance endurance performance.
      Therefore, the first issue in this review is to critically evaluate the available
      evidence for a potential endurance performance enhancement after long-term fat
      rich diet adaptation. Attainment of optimal performance is among other factors
      dependent also on the quality and quantity of the training performed. When
      exercise intensity is increased, there is an increased need for carbohydrates. On
      the other hand, consumption of a fat-rich diet decreases the storage of glycogen
      in both muscle and liver. Therefore, training intensity may be compromised in
      individuals while consuming a fat-rich diet. During submaximal exercise, fat for
      oxidation in muscle is recruited from plasma fatty acids, plasma triacylglycerol,
      and muscle triacylglycerol: the final question addressed in this review is which
      of these source(s) of fat contributes to the increased oxidation of fat during
      submaximal exercise after long-term fat diet adaptation.

PMID- 12218746
TI  - Exercise, diet, and skeletal muscle gene expression.
AB  - Skeletal muscle, as a consequence of its mass and great capacity for altered
      metabolism, has a major impact on whole-body metabolic homeostasis and is capable
      of remarkable adaptation in response to various physiological stimuli, including
      exercise and dietary intervention. Exercise-induced increases in skeletal muscle
      mRNA levels of a number of genes have been reported, due to transcriptional
      activation and/or increased mRNA stability. The cellular adaptations to exercise
      training appear to be due to the cumulative effects of transient increases in
      gene transcription after repeated exercise bouts. The relative importance of
      transcriptional (mRNA synthesis) and translational (mRNA stability or
      translational efficiency) mechanisms for the training-induced increases in
      skeletal muscle protein abundance remains to be fully elucidated. Dietary
      manipulation, and the associated alterations in nutrient availability and hormone
      levels, can also modify skeletal muscle gene expression, although fewer studies
      have been reported. A major challenge is to understand how exercise and diet
      exert their effects on gene and protein expression in skeletal muscle. In
      relation to exercise, potential stimuli include stretch and muscle tension, the
      pattern of motor nerve activity and the resultant calcium transients, the energy
      charge of the cell and substrate availability, oxygen tension and circulating
      hormones. These are detected by various cellular signaling mechanisms, acting on
      a range of downstream targets and a wide range of putative transcription factors.
      A key goal in the years ahead is to identify how alterations at the level of gene
      expression are coupled to the changes in skeletal muscle phenotype. It is clear
      that gene expression, although representing a specific site of regulation, is
      only one step in a complex cascade from the initial stimulus to the final
      phenotypic adaptation and integrated physiological response.

PMID- 12218747
TI  - Relationships between surface-detected EMG signals and motor unit activation.
AB  - INTRODUCTION: Surface-detected electromyographic (S-EMG) signals are used in
      exercise science to assess the extent of muscle activation, muscle fatigue, and
      neural activity during muscle contraction. However, the relationship has not been
      studied between S-EMG signal amplitude and motor unit activation at different
      muscle force levels. METHODS: S-EMG signals were measured from 76 healthy
      subjects during target force levels of 5, 10, 20, 30, and 50% of maximal
      voluntary contraction (MVC) of the knee extensors over 20-30 s. Mean absolute S
      EMG amplitude, surface-detected motor unit action potential amplitude (S-MUAP),
      motor unit mean firing rate (mFR), and motor unit mean voltage, which is the
      product of S-MUAP amplitude and mFR, were assessed in the vastus medialis by
      using EMG signal-decomposition and spike-triggered averaging techniques. RESULTS:
      Motor unit mean voltage increased to the same degree as mean absolute S-EMG
      amplitude with increasing force, implying that motor unit size and firing rate
      explain the increase in mean absolute S-EMG amplitude with increasing force
      generation. In addition, mean absolute S-EMG amplitude increased linearly during
      the course of each 20-30 s contraction, with the slope being greater at higher
      force levels. A small change was observed in the shape of needle-detected motor
      unit action potentials during the contraction, but this change was not sufficient
      to explain the large change in mean absolute S-EMG amplitude during the
      contraction. CONCLUSION: Mean absolute S-EMG amplitude at different force levels
      and its changes during the course of a submaximal contraction are dependent on
      the number of motor units active, their size, and firing rates.

PMID- 12218748
TI  - The acute effects of prior cycling cadence on running performance and kinematics.
AB  - PURPOSE: To determine if cycling cadence affects subsequent running speed through
      changes in stride frequency. METHODS: Thirteen male triathletes completed three
      sessions of testing on separate days. During the first session (control
      condition), the participants completed a 30-min cycling bout of high intensity at
      their preferred cadence, immediately followed by a 3200-m run at race effort.
      During the second and third sessions (fast condition and slow condition), the
      participants repeated the protocol but with a cycling cadence 20% faster or 20%
      slower than the control condition. RESULTS: After cycling at a fast cadence, the
      3200-m run time averaged nearly a min faster than after cycling at a slow
      cadence. Running stride frequency after cycling at a fast cadence was
      significantly greater than after cycling at a normal or slow cadence. Stride
      length did not differ between conditions. Joint kinematics at foot strike, mid
      stance, toe-off, and mid-swing were not different between conditions. CONCLUSION:
      Increased cycling cadence immediately before running increased stride frequency
      and, as a result, increased speed.

PMID- 12218749
TI  - Effect of four-month vertical whole body vibration on performance and balance.
AB  - PURPOSE: This randomized controlled study was designed to investigate the effects
      of a 4-month whole body vibration-intervention on muscle performance and body
      balance in young, healthy, nonathletic adults. METHODS: Fifty-six volunteers (21
      men and 35 women, aged 19-38 yr) were randomized to either the vibration group or
      control group. The vibration-intervention consisted of a 4-month whole body
      vibration training (4 min.d(-1), 3-5 times a week) employed by standing on a
      vertically vibrating platform. Five performance tests (vertical jump, isometric
      extension strength of the lower extremities, grip strength, shuttle run, and
      postural sway on a stability platform) were performed initially and at 2 and 4
      months. RESULTS: Four-month vibration intervention induced an 8.5% (95% CI, 3.7
      13.5%, P=0.001) net improvement in the jump height. Lower-limb extension strength
      increased after the 2-month vibration-intervention resulting in a 3.7% (95% CI,
      0.3-7.2%, P=0.034) net benefit for the vibration. This benefit, however,
      diminished by the end of the 4-month intervention. In the grip strength, shuttle
      run, or balance tests, the vibration-intervention showed no effect. CONCLUSION:
      The 4-month whole body vibration-intervention enhanced jumping power in young
      adults, suggesting neuromuscular adaptation to the vibration stimulus. On the
      other hand, the vibration-intervention showed no effect on dynamic or static
      balance of the subjects. Future studies should focus on comparing the performance
      enhancing effects of a whole body vibration to those of conventional resistance
      training and, as a broader objective, on investigating the possible effects of
      vibration on structure and strength of bones, and perhaps, incidence of falls of
      elderly people.

PMID- 12218750
TI  - Altering muscle activity in the lower extremities by running with different
      shoes.
AB  - PURPOSE: To provide evidence that lower-extremity muscle activity during running
      is tuned in response to the loading rate of the impact forces at heel-strike.
      METHODS: Six runners ran two 30-min trials per week for 4 wk. The trials tested
      two shoes which differed only in the material hardness of the midsole. The shoes
      were tested in a randomized sequence. Bipolar surface EMG was recorded from the
      muscles of the rectus femoris, biceps femoris, medial gastrocnemius, and tibialis
      anterior. EMG was resolved into time-frequency space using wavelet techniques.
      EMG was analyzed for the 150 ms time window immediately before heel-strike.
      RESULTS: The intensity of the EMG and the ratio of the EMG intensity between high
      and low frequency components both showed significant changes between shoes,
      subjects, and muscles. Additionally, the intensity ratio showed a significant
      change over the course of each 30-min run. CONCLUSIONS: Lower-extremity muscle
      activity used to tune the muscles for the impact task can be altered by changing
      the material hardness of the shoe. The changes in the EMG frequency ratio suggest
      that muscle fiber-type recruitment patterns can also be altered by the choice of
      midsole material.

PMID- 12218751
TI  - Technical reliability of the CSA activity monitor: The EarlyBird Study.
AB  - PURPOSE: To evaluate the technical performance of the CSA accelerometer-based
      activity monitor. METHODS: Twenty-three CSA monitors were subjected to intra- and
      inter-instrument variability tests by controlled trials using a motorized
      turntable. The CSA monitor measures change in acceleration, and precision was
      tested by producing sinusoidal variations in speed around two fixed baseline
      speeds (fast and medium). The angle of the monitor to the line of force along the
      radius of the turntable was varied using tilted blocks. Three sets of tests were
      carried out. 1. Intra-instrument variability: seven monitors were tested three
      times in each of the four quadrants. 2. All 23 monitors were used for inter
      instrument tests. 3. The effects of tilt at 15 degrees, 30 degrees, and 45
      degrees were carried out on six monitors. RESULTS: Intra-instrument coefficients
      of variation (CV) never exceeded 2% for fast or medium speed and achieved
      "between run" intra-class correlation coefficients (ICC) of 0.92 and 0.84
      respectively. There were no significant differences between the monitors in terms
      of repeatability (fast: = 0.97, medium: = 0.77). Although there were significant
      differences between monitors in terms of mean score, inter-instrument variability
      did not exceed 5% at either speed. Inter-batch ICCs ranged from 0.87 to 0.98 for
      fast and from 0.71 to 0.99 for medium. The angle test results corresponded
      closely to those predicted theoretically, with a loss in mean score of only 6%
      when the monitor was tilted from 0 degrees to 15 degrees. CONCLUSION: The CSA
      monitor provides a precise tool for measuring changes in acceleration in
      laboratory settings. Technically, the device performs well, and is likely to
      prove a useful tool in the assessment of physical activity in children and
      adults.

PMID- 12218762
TI  - Toward universal design in assessing health care experiences.

PMID- 12218763
TI  - The road to eliminating disparities in health care.

PMID- 12218764
TI  - Health plan selection criteria by people with impaired mobility.
AB  - BACKGROUND: Many decision-support tools for consumers selecting a health plan
      include a module measuring peer-group satisfaction with service and quality of
      care. The most widely used tools are sufficient for most people, but fail to
      report measures that are important to many individuals with disabilities.
      OBJECTIVES: To elicit health plan selection and assessment criteria by groups of
      people with one type of functional impairment arising from different origins.
      RESEARCH DESIGN: Observational study and qualitative analysis of structured focus
      groups. Content analysis of CAHPS survey instruments. SUBJECTS: Each participant
      had a mobility impairment arising from spinal cord injury, cerebral palsy,
      rheumatoid arthritis, or multiple sclerosis. Each participant had a choice of
      health plans. Focus groups were conducted in Phoenix, Philadelphia, and
      Washington DC. RESULTS: People with mobility impairments arising from the studied
      conditions desire comparative health plan information on the reliability of
      transportation to medical appointments, the ability to use an experienced and
      knowledgeable specialist as a primary provider, and accessible buildings and
      examination equipment. This study population also seeks information about the
      experience of their peers in each health plan, especially about benefits
      administration. CONCLUSIONS: People with mobility impairments arising from spinal
      cord injury, cerebral palsy, multiple sclerosis, or rheumatoid arthritis
      currently have little information and little bona fide choice of health plans and
      physicians. This group of people seeks specific information within the areas of
      benefit coverage, benefits interpretation and administration, provider panels,
      accessibility to clinics and equipment, and how to navigate the health plan's
      grievance and appeals process.

PMID- 12218765
TI  - Effect of managed care insurance on the use of preventive care for specific
      ethnic groups in the United States.
AB  - BACKGROUND: Ethnic disparities in access to health care is a persistent problem
      in the US. Despite the broad implementation of managed care, there is little
      information that specifically addresses how this type of coverage may affect
      ethnic disparities. OBJECTIVES: To examine the effect of managed care insurance
      on the use of preventive care for different ethnic groups. RESEARCH DESIGN:
      Observational cohort using the 1996 Medical Expenditure Panel Survey. SUBJECTS:
      Adults with health insurance who report their ethnicity as white, black,
      Hispanic, or Asian/Pacific Islander. MAIN OUTCOME MEASURES: (1) Mammography
      within the past 2 years for women between 50 and 75 years of age; (2) clinical
      breast exam within the past 2 years for women between 40 and 75 years; (3)
      Papanicolaou smear within the past 2 years for women between 18 and 65 years; and
      (4) cholesterol screening within the past 5 years for men and women older than
      the age of 20 years. RESULTS: Hispanic people enrolled in a managed care plan
      report higher rates of mammography, breast exam, and Papanicolaou smear compared
      with Hispanic people with fee-for-service insurance. For example, the adjusted
      predicted probability of a mammogram for Hispanic women with managed care was
      85.6% compared with 72.4% for Hispanic women with fee-for-service coverage (risk
      difference: 13.2%; 95% CI for the risk difference 0.7%-25.7%). White persons with
      managed care are also more likely than white persons with fee-for-service
      coverage to receive mammography and cholesterol screening. Managed care is not
      associated with less preventive care for any ethnic group. CONCLUSIONS: In this
      nationally representative household survey, it was found that managed care is
      associated with greater use of some preventive care for Hispanic persons and
      white persons than fee-for-service insurance. Despite a focus on prevention, the
      benefits of managed care are not apparent for black persons or Asian/Pacific
      Islanders.

PMID- 12218766
TI  - Effects of efforts to increase response rates on a workplace chronic condition
      screening survey.
AB  - OBJECTIVE: Expanded health risk appraisal (HRA) surveys can help employers target
      chronic conditions for outreach or disease management interventions by providing
      data on the prevalences of conditions and their effects on work performance.
      However, concerns exist about the accuracy of this data because most HRAs have
      low response rates. We evaluated these concerns by examining the prevalences and
      work impairments associated with chronic conditions across four HRA subsamples
      that differed in intensity of recruitment effort. METHODS: Two thousand five
      hundred thirty-nine working people were invited to complete an expanded HRA
      survey that included questions about chronic conditions, work impairments, and
      demographics. Condition prevalences and associations between conditions and work
      impairment were compared across subsamples who responded after a single mailing,
      after two mailings, and in a telephone interview after the mailings either with
      or without a 20 dollars incentive. RESULTS: Consistent with previous research,
      response rates varied dramatically across the four subsamples (from 20.1% with
      only one mailing to 67.7% with telephone administration and a financial
      incentive). However, the estimated prevalences of chronic conditions, levels of
      work impairment, and effects of chronic conditions on work impairment did not
      differ with intensity of recruitment effort. CONCLUSIONS: Expanded HRAs can
      provide useful data on the prevalences and work impairments associated with
      chronic conditions even if response rates are low. Confirmation of these results
      is required, however, in new samples. Additional research is also needed on
      innovative and cost-effective strategies to improve HRA response rates.

PMID- 12218767
TI  - What patient population does visit-based sampling in primary care settings
      represent?
AB  - BACKGROUND: Evaluations of outpatient interventions often rely on consecutive
      sampling of clinic visitors, and assume that study results generalize to the
      population of patients cared for. OBJECTIVE: The representativeness of such visit
      based sampling compared with the population of patients seen during the same
      year, in terms of sociodemographic and clinical characteristics of the user
      groups that visit-based sampling yielded were assessed. METHODS: One thousand
      five hundred forty-six continuing patients visiting the primary care firms in an
      urban VA medical center were consecutively sampled, and visit frequencies were
      compared for these patients with subsets of the patient population.
      Administrative and survey data was then used to describe the types of patients
      visit-based sampling most represented compared with the types of patients sampled
      less frequently. RESULTS: The average sampled patient visited the firms
      significantly more often than patients in the reference population (18.7 vs.
      9.5). Sampled patients were significantly older (>55 years), in poorer health
      (higher prevalence of cancer, stroke, hypertension), less likely to smoke, and
      more likely to be single than the average patient visiting the firms (P<0.05).
      Adjusting for age and sickness, frequent visitors were more apt to have
      experienced continuity of care during the prior year, to prefer VA care, and to
      be unemployed. CONCLUSIONS: Consecutive visit-based sampling actually selected
      patients with a visit pattern more typical of the patient population visiting
      four or more times a year. Studies using sampling of consecutive visitors will
      typically under-represent low users of care and should account for the degree to
      which results may not generalize to the broader practice population.

PMID- 12218768
TI  - Six-item screener to identify cognitive impairment among potential subjects for
      clinical research.
AB  - OBJECTIVE: To design a brief cognitive screener with acceptable sensitivity and
      specificity for identifying subjects with cognitive impairment. DESIGN: Cohort
      one is assembled from a community-based survey coupled with a second-stage
      diagnostic evaluation using formal diagnostic criteria for dementia. Cohort two
      is assembled from referrals to a specialty clinic for dementing disorders that
      completed the same diagnostic evaluation. SETTING: Urban neighborhoods in
      Indianapolis, Indiana and the Indiana Alzheimer Disease Center. PATIENTS: Cohort
      one consists of 344 community-dwelling black persons identified from a random
      sample of 2212 black persons aged 65 and older residing in Indianapolis; cohort
      two consists of 651 subject referrals to the Alzheimer Disease Center.
      MEASUREMENTS: Formal diagnostic clinical assessments for dementia including
      scores on the Mini-mental state examination (MMSE), a six-item screener derived
      from the MMSE, the Blessed Dementia Rating Scale (BDRS), and the Word List
      Recall. Based on clinical evaluations, subjects were categorized as no cognitive
      impairment, cognitive impairment-not demented, or demented. RESULTS: The mean age
      of the community-based sample was 74.4 years, 59.4% of the sample were women, and
      the mean years of education was 10.1. The prevalence of dementia in this sample
      was 4.3% and the prevalence of cognitive impairment was 24.6%. Using a cut-off of
      three or more errors, the sensitivity and specificity of the six-item screener
      for a diagnosis of dementia was 88.7 and 88.0, respectively. In the same sample,
      the corresponding sensitivity and specificity for the MMSE using a cut-off score
      of 23 was 95.2 and 86.7. The performance of the two scales was comparable across
      the two populations studied and using either cognitive impairment or dementia as
      the gold standard. An increasing number of errors on the six-item screener is
      highly correlated with poorer scores on longer measures of cognitive impairment.
      CONCLUSIONS: The six-item screener is a brief and reliable instrument for
      identifying subjects with cognitive impairment and its diagnostic properties are
      comparable to the full MMSE. It can be administered by telephone or face-to-face
      interview and is easily scored by a simple summation of errors.

PMID- 12218769
TI  - Development of a method to identify seniors at high risk for high hospital
      utilization.
AB  - BACKGROUND: A small percentage of older persons account for most Medicare costs.
      If persons at high risk for high health care utilization can be identified,
      resources can be directed to improve their health care and reduce utilization.
      OBJECTIVE: To develop an efficient and economical approach to identifying older
      persons at risk for high future health care utilization. DESIGN: Validation
      cohort. SETTING: Three communities. SUBJECTS: Five thousand one hundred thirty
      eight community-dwelling persons aged 71 years or older. MAIN OUTCOME MEASURES:
      High utilization (defined as >or=11 hospital days during 3 years) and overall
      Part A Medicare hospital costs during 3 years. RESULTS: Predictive multivariable
      models were created that relied on prior hospitalization only, self-report only,
      and combined self-report and physical examination/lab data. Ten self-report items
      (hospitalizations in prior year and year before that, male gender, fair/poor
      health, not working, infrequent religious participation, needing help bathing,
      unable to walk 1/2 mile, diabetes, and taking loop diuretics) and two lab tests
      (low serum albumin and iron) remained as independent predictors of high
      utilization. Based upon these variables, approximately 1/4 of the population was
      identified as being at high risk (>or=0.28 probability) for high health care
      utilization and those identified accounted for approximately half of all Medicare
      Part A costs for the entire population. Finally, a two-phase strategy was
      developed in which tests are only administered to individuals whose risk cannot
      be adequately determined by self-report variables (approximately 1/4 of
      subjects). CONCLUSIONS: Simple questions and laboratory tests can accurately and
      efficiently identify seniors at high risk for high health care utilization.

PMID- 12218770
TI  - Patient adherence and medical treatment outcomes: a meta-analysis.
AB  - BACKGROUND: Adherence is a factor in the outcome of medical treatment, but the
      strength and moderators of the adherence-outcome association have not been
      systematically assessed. OBJECTIVES: A quantitative review using meta-analysis of
      three decades of empirical research correlating adherence with objective measures
      of treatment outcomes. METHOD: Sixty-three studies assessing patient adherence
      and outcomes of medical treatment were found involving medical regimens
      recommended by a nonpsychiatrist physician, and measuring patient adherence and
      health outcomes. Studies were analyzed according to disease (acute/chronic,
      severity), population (adult/child), type of regimen (preventive/treatment, use
      of medication), and type and sensitivity of adherence and outcomes measurements.
      RESULTS: Overall, the outcome difference between high and low adherence is 26%.
      According to a stringent random effects model, adherence is most strongly related
      to outcomes in studies of nonmedication regimens, where measures of adherence are
      continuous, and where the disease is chronic (particularly hypertension,
      hypercholesterolemia, intestinal disease, and sleep apnea). A less stringent
      fixed effects model shows a trend for higher adherence-outcome correlations in
      studies of less serious conditions, of pediatric patients, and in those studies
      using self-reports of adherence, multiple measures of adherence, and less
      specific measures of outcomes. Intercorrelations among moderator variables in
      multiple regression show that the best predictor of the adherence-outcome
      relationship is methodological-the sensitivity/quality of the adherence
      assessment.

PMID- 12218771
TI  - Multidimensional adaptive testing for mental health problems in primary care.
AB  - OBJECTIVES: Efficient and accurate instruments for assessing child
      psychopathology are increasingly important in clinical practice and research. For
      example, screening in primary care settings can identify children and adolescents
      with disorders that may otherwise go undetected. However, primary care offices
      are notorious for the brevity of visits and screening must not burden patients or
      staff with long questionnaires. One solution is to shorten assessment
      instruments, but dropping questions typically makes an instrument less accurate.
      An alternative is adaptive testing, in which a computer selects the items to be
      asked of a patient based on the patient's previous responses. This research used
      a simulation to test a child mental health screen based on this technology.
      RESEARCH DESIGN: Using half of a large sample of data, a computerized version was
      developed of the Pediatric Symptom Checklist (PSC), a parental-report
      psychosocial problem screen. With the unused data, a simulation was conducted to
      determine whether the Adaptive PSC can reproduce the results of the full PSC with
      greater efficiency. SUBJECTS: PSCs were completed by parents on 21,150 children
      seen in a national sample of primary care practices. RESULTS: Four latent
      psychosocial problem dimensions were identified through factor analysis:
      internalizing problems, externalizing problems, attention problems, and school
      problems. A simulated adaptive test measuring these traits asked an average of
      11.6 questions per patient, and asked five or fewer questions for 49% of the
      sample. There was high agreement between the adaptive test and the full (35-item)
      PSC: only 1.3% of screening decisions were discordant (kappa = 0.93). This
      agreement was higher than that obtained using a comparable length (12-item) short
      form PSC (3.2% of decisions discordant; kappa = 0.84). CONCLUSIONS:
      Multidimensional adaptive testing may be an accurate and efficient technology for
      screening for mental health problems in primary care settings.

PMID- 12218772
TI  - Process of care in Hispanic, black, and white VA beneficiaries.
AB  - OBJECTIVE: To examine whether process of hospital care differs among Hispanic,
      black, and white VA beneficiaries. SUBJECTS: Two thousand eight-hundred fifty-two
      Hispanic, black, and white male VA beneficiaries from a case-control study
      discharged alive from one of twelve southern veterans hospitals with one of three
      diagnoses, diabetes mellitus (DM), congestive heart failure (CHF), or chronic
      obstructive pulmonary disease (COPD). METHODS: We applied diagnosis-specific
      explicit criteria for the process of hospital care to each patient's hospital
      record and computed the adherence score; the percentage of applicable criteria
      performed during the hospital stay. We compared mean scores in Hispanic, black,
      and white patients and then compared adjusted scores using multiple linear
      regression. MAIN OUTCOME MEASURE: Process of inpatient care (adherence score) in
      Hispanic, black, and white patients at admission, treatment, and discharge.
      RESULTS: Mean admission adherence scores differed (P = 0.003) among Hispanic
      patients, black patients, and white patients for CHF and COPD, but not DM. Mean
      treatment and discharge scores were not different among Hispanic patients, black
      patients, and white patients. In bivariate comparisons, mean admission scores
      were higher in black patients compared with white patients for CHF (P= 0.003) and
      COPD (P= 0.01). In stratified analyses, admission and treatment scores were
      higher (P= 0.0001) in patients admitted to teaching compared with nonteaching
      hospitals. Process of inpatient care did not differ among Hispanic, black, and
      white patients after adjusting for admission to a teaching hospital and other
      covariates. CONCLUSION: In contrast to findings in other studies, process of
      inpatient care was generally similar in Hispanic patients, black patients, and
      white patients. Our findings may reflect several characteristics of veterans'
      hospitals that may lead to care that is more equitable.

PMID- 12218773
TI  - Randomized trial of 5 dollars versus 10 dollars monetary incentives, envelope
      size, and candy to increase physician response rates to mailed questionnaires.
AB  - BACKGROUND: The validity of the results of mailed surveys is often threatened by
      nonresponse bias, which is made more likely when response rates are low. However,
      the effectiveness and cost-effectiveness of several strategies to increase
      response rates are uncertain. OBJECTIVES: To assess three strategies to increase
      response rates to mailed physician surveys: including a 10 dollars versus a 5
      dollars cash incentive in the initial mailing, including a mint candy or not, and
      using a large versus small outgoing envelope. RESEARCH DESIGN AND SUBJECTS: Using
      a 2 x 2 x 2 factorial design, a randomized trial of these strategies was
      conducted in a survey of 1200 physicians randomly selected from the American
      Medical Association's Master File. RESULTS: Including a 10 dollars incentive
      yielded a significantly higher response rate (60.5% vs. 52.8%) (P = 0.009). The
      mailing and incentive costs per completed response were 12.24 dollars (95% CI,
      11.75 dollars, 13.64 dollars) in the 5 dollars group and 18.48 dollars (95% CI,
      17.77 dollars, 20.69 dollars) in the 10 dollars group. Each additional response
      obtained in the 10 dollars group came at an incremental cost of 61.26 dollars
      (95% CI, 36.98 dollars, 200.80 dollars). Neither inclusion of a mint nor use of a
      large envelope influenced the response rate. CONCLUSIONS: Investigators may
      increase response rates by including more money in the initial questionnaire
      packet, but there may be diminishing returns to serial increments in incentives
      greater than 5 dollars. Including smaller incentives in more questionnaires may
      maximize total responses.

PMID- 12218774
TI  - Economic messages in prescription drug advertisements in medical journals.
AB  - BACKGROUND: The extent to which pharmaceutical companies promote the economic
      advantages of their products in advertisements in medical journals, and whether
      such claims are supported by evidence, has not been quantified. Our objectives
      were to examine how often prescription drug advertisements in leading medical
      journals contain economic messages, and to determine the types of promotional
      claims made and whether supporting evidence is provided. METHODS: All
      prescription drug advertisements appearing in six leading general medical and
      specialty journals in 3 selected months annually from 1990 to 1999 were reviewed.
      Using a standard data collection form, two reviewers examined each ad for
      economic content-including mention of the drug's price, value, cost saving, or
      cost-effectiveness. RESULTS: Economic messages appeared in 237 (11.1%) of the
      2144 advertisements examined. Proportion of ads with economic content has
      increased over time (P = 0.003). Most frequently, economic ads contained
      statements that drugs were "less expensive" or "cost less" than alternative
      treatments (50.6% of economic ads). Supporting evidence for economic claims was
      clearly reported in 63.7% of cases, and typically referred to published drug
      prices rather than more detailed economic analysis. Ads for calcium channel
      blocking agents and ACE inhibitors frequently contained economic messages.
      CONCLUSIONS: Economic messages about prescription drugs are used in
      advertisements in leading medical journals and their frequency may be rising.
      Physicians should be aware of this phenomenon, and its potential impact on their
      prescribing decisions. More scrutiny of the supporting evidence underlying
      economic claims by the medical community and regulators may be needed.

PMID- 12218775
TI  - Characterization of CD8(-) HLA class I/epitope tetrameric complexes binding T
      cells.
AB  - Antigen-specific CD8-expressing T cells play a crucial role in the host's defense
      against viral disease and malignancy. Epitope-specific CD8(+)T cell responses to
      malignant and viral disease can be accurately measured using tetramers (tHLA) of
      HLA class I molecules loaded with antigenic peptides. In addition, tHLA have been
      used to evaluate immune responses to antigen-specific immunization. tHLA bind
      specifically to complementary T-cell receptor (TCR) structures on the surface of
      T cells expressing the CD8 coreceptor. Surprisingly, however, CD8(-) cells
      binding tHLA are often observed. This study uses four-color flow cytometry to
      show that HLA-A*0201-tHLA-stained CD8(-) cells can be divided into two subsets:
      87% represent B-lymphocytes (CD19(+), CD45RA(+), HLA-DR(+), and CD20(+)), and 13%
      represent T-helper cells (CD3(+), CD4(+), CD45RA(+), and CD27(+)). This
      phenomenon is not HLA-restricted because it could be observed even in peripheral
      blood mononuclear cells (PBMC) from a non HLA-A*0201-expressing healthy donor. In
      addition, no T-cell receptor was detected on the B-lymphocytes. Retrospective
      enumeration of vaccine-induced CD8(-) tHLA cells in 243 PBMC samples from 36
      patients with melanoma undergoing peptide vaccination revealed that tHLA staining
      is not dependent on immunization status or the presence of CD8(+) tHLA(+) T
      cells. These findings, suggest that the nonspecific binding of tHLA to non-TCR
      expressing T cells requires a careful interpretation of results and further steps
      in preparation of sample for tHLA-based sorting of epitope specific T cells.

PMID- 12218776
TI  - Biodistribution and retention time of retrovirally labeled T lymphocytes in mice
      is strongly influenced by the culture period before infusion.
AB  - T lymphocytes used for adoptive immunotherapy are often cultured before transfer
      to generate sufficient amounts of effector cells with desired specificity.
      Modification of lymphocytes induced by in vitro activation and expansion may
      influence their potential effector capacity by altering the survival and
      trafficking patterns after transfer. In this report, the authors show that the
      culture period of T cells after ConA/IL-2 stimulation strongly influences the
      retention and tissue distribution of these cells after infusion into syngeneic
      C57BL/6 mice. Infused labeled cells that have been cultured for 3 days remained
      in the peripheral blood and organs in at least a ten-fold higher number than
      cells cultured for 8 days. In addition, cells cultured for 3 days preferentially
      migrate to lungs and liver shortly after infusion and subsequently to lymph nodes
      and spleen. Cells cultured for 8 days preferentially migrate to liver and can be
      hardly detected in lymph nodes. In contrast, labeled cells cultured for 3 days
      are predominantly present in lymph nodes starting from day 8 until day 28. We
      showed that accurate monitoring of transferred cells is feasible, which may
      contribute to understanding response to adoptive immunotherapy.

PMID- 12218777
TI  - Enhancing tumor targeting and apoptosis using noncovalent antibody homodimers.
AB  - A rare type of antibody that spontaneously binds to each self (homodimerizes) has
      been described. This self-binding (autophilic) antibody provides stronger
      protection against bacterial infection than a non self-binding antibody with
      identical specificity and affinity due to increase of polymeric avidity. A
      peptide derived from the self-binding domain of the autophilic antibody was
      crosslinked to the Fc carbohydrate of two monoclonal antibodies specific for the
      B-cell receptor (BCR) of a murine and a human B-cell tumor. Peptide-crosslinked
      antibodies bind to themselves on solid phase ELISA as homodimer and establish in
      solution a monomer-dimer equilibrium. Autophilic antibodies bind to their
      respective tumor target cells with increased efficiency as determined by FACS
      analysis. They also induce twice the amount of apoptosis of target tumor cells
      than the control antibodies. Furthermore, the modified antibodies inhibit tumor
      growth in culture more efficiently than the control antibodies. Criss-cross
      protocols in FACS, apoptosis, and growth inhibition indicate the specificity of
      targeting the BCR with autophilic antitumor antibodies. The chemical approach of
      increasing the binding of antibodies without creating chemically crosslinked
      dimers mimics naturally occurring autophilic antibodies and represents a simple
      and attractive alternative to chemical dimerizing and antibody engineering
      techniques for improving their antitumor effect. Furthermore, these results
      provide a guide to incorporate the self-binding peptide into the structure of
      antibodies using modeling and molecular crafting techniques.

PMID- 12218778
TI  - Efficacy of adjuvant immunochemotherapy with OK-432 for patients with curatively
      resected gastric cancer: a meta-analysis of centrally randomized controlled
      clinical trials.
AB  - The benefit of immunochemotherapy employing a streptococcal preparation, OK-432
      (Picibanil), in patients with curatively resected gastric cancer was reassessed
      by meta-analysis of data from 1,522 patients enrolled in six clinical trials with
      central randomization. All six trials began between 1985 and 1993, and patients
      were followed-up for at least 3 years after surgery and enrollment of the last
      patient. In these trials, standard chemotherapy was compared with the same
      chemotherapy plus OK-432. The endpoint was overall survival and intent-to-treat
      analysis was done without patient exclusion. Data were analyzed using the Mantel
      Haenszel method. The 3-year survival rate for all eligible patients in the six
      trials was 67.5% in the immunochemotherapy group versus 62.6% in the chemotherapy
      group. The 3-year overall survival odds ratio was 0.81 (95% confidence interval:
      0.65-0.99). The treatment effect was shown to be statistically significant (p =
      0.044). The results of this meta-analysis suggest that immunochemotherapy after
      surgery with OK-432 can improve the survival of patients with curatively resected
      gastric cancer.

PMID- 12218779
TI  - Oral administration of freshly expressed juice of Echinacea purpurea herbs fail
      to stimulate the nonspecific immune response in healthy young men: results of a
      double-blind, placebo-controlled crossover study.
AB  - Echinacea extracts are widely used in European countries and in the United States
      as "immune-stimulating" agents. Even though the evidence to stimulate certain
      components of the nonspecific immune system (phagocytosis, macrophages, and
      production of cytokines) stems from in vitro experiments or studies after
      parenteral application, the commercially available Echinacea preparations used as
      drugs or supplements are for oral use. The aim of the study was to determine
      whether phagocytic activity and production of cytokines is stimulated by oral
      application of a commercially available Echinacea preparation. Forty healthy male
      volunteers (ages 20-40 years) participated in the study. They received either a
      freshly expressed juice of Echinacea purpurea herbs or placebo juice using a
      double-blind placebo-controlled crossover design with two treatment periods of 14
      days and a wash-out period of 4 weeks in between. Endpoints for immune
      stimulation: phagocytic activity of polymorphonuclear leukocytes and monocytes
      measured by flowcytometry, production of tumor necrosis factor alpha (TNF)-alpha
      and Interleukin (IL)-1beta by LPS-stimulated blood monocytes. Echinacea purpurea
      herbs did neither enhance phagocytic activity of polymorphonuclear leukocytes nor
      that of monocytes when compared with placebo. Echinacea purpurea herbs did not
      influence the production TNF-alpha and IL-1beta by LPS-stimulated monocytes.
      Unexpectedly, Echinacea purpurea herbs decreased serum ferritin concentration (p
      = 0.0005). All other laboratory and safety data remained unchanged. The "immune
      stimulation" by Echinacea purpurea observed in vitro and after parenteral
      administration are not confirmed in healthy humans after oral intake. Other
      immunomodulatory effects may explain the benefits of Echinacea preparations in
      reducing duration and severity of upper-respiratory tract infections found in
      randomized, double-blind clinical trials.

PMID- 12218780
TI  - The treatment of patients with disseminated malignant melanoma by vaccination
      with autologous cell hybrids of tumor cells and dendritic cells.
AB  - Malignant melanoma has been shown to be susceptible to T cell-mediated immunity
      and, therefore, is a candidate for vaccination approaches. Clinical trials using
      dendritic cells (DC) loaded with peptides corresponding to tumor antigens are
      ongoing in several institutions, and some promising results have already been
      published. However, every single peptide-based vaccine can only be used in a
      patient with a given single HLA type, and this strategy is not appropriate for
      patients with rare HLA types or with tumors without defined antigens. A clinical
      pilot study in patients with disseminated melanoma refractory to standard therapy
      was initiated using a different approach. The authors generated autologous
      monocyte-derived DC and fused these DC with gamma-irradiated primary autologous
      tumor cells by incubation in polyethylene glycol. In previous experiments, the
      authors had shown that these fused cell products are potent inducers of a T-cell
      response in a mixed lymphocyte tumor cell culture. Seventeen patients were
      immunized with the cell product by s.c. injection in monthly intervals without
      any serious side effects. Of these patients, one had a partial response with
      decrease in size of all evaluable tumor manifestations. In one patient, some of
      the metastases were regressing despite an overall progressive disease, and one
      patient achieved disease stabilization for six months. In the responding patient,
      in parallel to tumor regression, circumscript hair depigmentation occurred. These
      data show, that a hybrid vaccine of DC and tumor cells can be safely applied and
      can induce tumor regressions, however, the clinical efficacy of the approach in
      its present form is insufficient.

PMID- 12218781
TI  - Phenotypical and functional characterization of clinical grade dendritic cells.
AB  - Dendritic cells (DC) are the professional antigen presenting cells of the immune
      system. Therefore, several clinical studies have been initiated in which tumor
      antigen-loaded DC are used as a vaccine to boost an immune response against
      malignant tumors in patients with cancer. A prerequisite for DC used in these
      vaccination studies is not only that they are grown under "Good Manufacturing
      Practice" but equally important that they retain their functional properties. In
      an extensive study, various conditions were tested to optimize the maturation and
      yield of DC grown for clinical use. DC grown in XVIVO-15 medium supplemented with
      5% HS yielded the best results, morphologically and phenotypically. Mature DC
      expressed significant amounts of mature DC markers (CD83) and the costimulatory
      molecules CD80 and CD86. It was shown that mature and immature DC can be frozen
      and retain their phenotype and function after thawing. These clinical grade DC
      secreted high levels of the chemokines dendritic cell chemokine 1 (DC-CK1),
      interleukin-8 (IL-8), macrophage-derived chemokine (MDC), and thymus and
      activation-regulated chemokine (TARC). This implicates that these DC can attract
      naive T and B cells as well as natural killer cells and memory T cells. Finally,
      to test their migratory capacity in vivo, (111)In-labeled DC were injected into
      tumor-free lymph nodes of patients with melanoma. Autoradiographic analysis of
      the dissected lymph nodes indicated that these DC could migrate into the T cell
      area of adjacent lymph nodes. In conclusion, a culture procedure was established
      to generate large numbers of monocyte-derived immature and mature DC that retain
      their morphologic, phenotypic, and functional characteristics in vitro and can be
      visualized in situ.

PMID- 12218782
TI  - Phase 1 clinical study of cyclophilin B peptide vaccine for patients with lung
      cancer.
AB  - Cyclophilin B (CypB) possesses two antigenic epitopes (CypB(84-92) and CypB(91
      99) ) recognized by HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes
      (CTLs). To determine the safety of CypB-derived peptides and its ability to
      generate antitumor immune responses, patients with advanced lung cancer received
      subcutaneous vaccinations of these peptides or their modified peptides. All 16
      patients were vaccinated with CypB(91-99) or its modified peptide, whereas only
      two patients were vaccinated with the modified CypB(84-92), as immediate-type
      hypersensitivity to CypB(84-92) or its modified peptide was observed in the
      remaining patients. No severe adverse events were associated with the
      vaccination. No significant increase in cellular responses to either peptides or
      tumor cells was observed in the postvaccination PBMCs by the conventional CTL
      assays in any patients tested. These results suggest that the vaccination of
      CypB(91-99) peptide was safe, but failed to induce objective immune responses at
      this regimen.

PMID- 12218783
TI  - Challenges, successes, and failures.

PMID- 12218784
TI  - Genetic and environmental risk factors for sagittal craniosynostosis.
AB  - The authors investigated whether genetic and environmental factors influence risk
      for sagittal craniosynostosis. Cases were ascertained from craniofacial clinics
      in the Baltimore-Washington metropolitan region. Controls were recruited from the
      Johns Hopkins newborn nursery and a large pediatric practice in Baltimore County.
      Forty-two probands with isolated, nonsyndromic sagittal craniosynostosis born in
      the mid-Atlantic region were included in this analysis. Controls are infants born
      in Maryland without any known birth defects (n = 182). Odds ratios (OR) and
      corresponding 95% confidence intervals (CI) were calculated. Cases were genotyped
      at several loci implicated in malformation syndromes including craniosynostosis.
      There were no elevated risks for craniosynostosis related to maternal or paternal
      smoking or maternal vitamin usage. Case mothers consumed less alcohol (OR = 0.38,
      95% CI = 0.17-0.85) and had less education than control mothers ( < 0.001). All
      cases that were sequenced were negative for mutations at the following genes:
      exon IIIa 755C->G, (exons IIIa and IIIc,), exon IIIa, and exon 1. These findings
      suggest that whereas TWIST and the genes are important for syndromic
      craniosynostosis, they are unlikely to be involved in isolated sagittal
      craniosynostosis. Parental education and alcohol consumption were associated with
      sagittal craniosynostosis in this study.

PMID- 12218785
TI  - Bone tissue engineering: treatment of cranial bone defects in rabbits using self
      reinforced poly-L,D-lactide 96/4 sheets.
AB  - This study is one of a series in which the authors evaluate various absorbable
      sheets to guide bone regeneration in cranial bone defects. The aim was to
      evaluate the use of self-reinforced poly-L,D-lactide 96/4 (SR-PLA96) sheets for
      cranial bone tissue engineering in experimental defects in rabbits. Square
      defects of 10 x 10 mm were created in the right parietal bone. SR-PLA96 implants
      (15 x 15 mm) were used to cover these defects in 12 New Zealand White rabbits.
      Similar defects were created in the left parietal bone, but no sheets were used
      (controls). The rabbits were killed after 6, 24, or 48 weeks. Histology and
      histomorphometry were used to evaluate healing of the defects. Defects covered
      with SR-PLA96 sheets showed more abundant bone formation than control (non
      covered) defects. At 6 weeks, the defects were occupied mainly by fibrous tissue.
      At 24 weeks, healing with bone formation was more obvious in the covered defects.
      At 48 weeks, bone completely bridged defects covered with SR-PLA96 sheets, and
      incomplete bridging was seen in non-covered control defects. Hence, bone tissue
      engineering in experimental cranial bone defects in rabbits can be achieved using
      SR-PLA96 sheets to guide bone regeneration.

PMID- 12218786
TI  - Age-related changes in anthropometric measurements in the craniofacial regions
      and in height in Down's syndrome.
AB  - This cross-sectional study analyzed age-related changes in normal and abnormal
      measurements of the head and face in three age categories in 115 Down's syndrome
      patients 1 to 36 years old. The frequency of normal measurements significantly
      surpassed that of abnormal ones in each category. Clinically, the key task was to
      ascertain differences between the youngest and oldest patients. In age group 1 (1
      to 5 years), normal measurements in three of the six craniofacial regions were
      significantly more frequent than abnormal ones. In age group 2 (6 to 15 years)
      the percentage of normal measurements significantly increased, influenced by
      higher growth rates in the period of maturation, which coincided with this
      category. In age group 3 (16 to 36 years) the percentage of normal measurements
      significantly increased in the head and ear but decreased in the other regions,
      significantly in the orbits. The frequency of both optimal and severely abnormal
      measurements changed significantly from age group 1 to 3 in only five
      measurements each, with no consistency in the direction of results. Abnormal
      measurements qualified as stigmata and were recorded in 40% (10 of 25) in five
      regions: three in the face; two in each of the head, orbits, and ears; and one in
      the nose. Marked epicanthi covering the endocanthion decreased from 35.0% in age
      group 1 to 8.7% in group 3. In age group 1, the frequency of normal body height
      (20.7%) in both sexes was significantly less than subnormal (70.3%) but
      significantly decreased in age group 2. Mean height in group 3 was enough to rule
      out short stature as a stigmata of Down's syndrome. The study was limited by
      small numbers, particularly in the variations of normal and abnormal, but the
      trend toward normality after maturation suggests that reconstructive surgery
      should be delayed until this time.

PMID- 12218787
TI  - CATCH 22 Syndrome.
AB  - CATCH 22 syndrome is characterized by cardiac defects, abnormal facial features,
      thymic hypoplasia, cleft palate, and hypocalcemia. It results from a deletion
      within chromosome 22q11. This syndrome is not a simple disease. It includes
      DiGeorge syndrome, conotruncal anomaly face syndrome, and velocardiofacial
      syndrome. The authors report two cases of CATCH 22 syndrome.

PMID- 12218789
TI  - Molding helmet therapy in the management of sagittal synostosis.
AB  - The current surgical treatment of sagittal craniosynostosis often fails to
      produce a normal cephalic index; however, recent reports of early endoscopic
      suture release and postoperative helmet therapy promise improved cranial
      symmetry. The role of helmet therapy is critical in this approach, but there are
      few reports on the use of helmet therapy after craniosynostosis surgery. The
      authors present a retrospective review comparing the results of surgery alone
      versus surgery and postoperative banding in treating children diagnosed with
      sagittal synostosis. Cephalic index (CI) measurements and the divergence of the
      CI from the norm (DFN) were used to compare the banded and the non-banded groups.
      Included in the study were 21 children with sagittal craniosynostosis of whom 6
      were treated with surgery alone and 15 were treated with surgery and
      postoperative banding. Preoperatively, both groups were significantly different
      from the norm (non-banded, P < 0.05; banded, P < 0.01), while postoperatively
      they were not significantly different from the norm. Statistically significant
      changes were present in the CIs of the banded group in the preoperative-follow-up
      interval (P < 0.01), while no significant changes occurred in the non-banded
      group during this same interval. Statistically significant changes in the DFN
      occurred in the preoperative-postoperative and preoperative-follow-up intervals
      of the banded group; however, these changes were not significant in the non
      banded group during the same intervals. Correction toward a normal CI was seen in
      the banded group throughout the course of treatment, while this trend was not
      present in the non-banded group. Therefore, molding helmet therapy maintains the
      operative correction obtained and promotes more normal cranial growth patterns.

PMID- 12218788
TI  - Soccer-related craniomaxillofacial injuries.
AB  - The authors assessed the rate of craniomaxillofacial fractures in soccer and the
      areas where they occur, describing above all the injury pattern of this sport.
      Over a 5-year period (1995-2000) 46 cases of 329 with fractures associated with
      different sports activities have been surgically operated at the maxillofacial
      surgery department of the Policlinico "Umberto I" Hospital, University "La
      Sapienza" of Rome. All data collected have been selected on the basis of sex,
      age, anatomic site of the fracture, and the practiced sport. Information on
      injury patterns, severity, and play circumstances have been documented. The
      department examined 7 sports disciplines, but soccer was responsible for sports
      related maxillofacial fractures in 34 of 46 cases (73.9%). All 34 fractures
      occurred to men. In soccer, the zygomatic and nasal regions are mainly involved.
      In fact the authors examined zygomatic fractures in 15 cases and nasal fractures
      in 10 cases. Direct contact between players generally causes soccer-related
      maxillofacial fractures: head-elbow impacts (21 cases) or head-head impacts (14
      cases). The male:female ratio is 6.6:1, while the average age is 25 years for
      males and 23 years for females. In comparison with other sports (rugby, football,
      etc.) where physical contact occurs more frequently and the higher incidence of
      traumatic events justifies the use of protective measures, soccer is not a
      particularly violent sport. In soccer, maxillofacial traumas are caused by
      violent impacts between players that take place mainly when the ball is played
      with the forehead. In this moment there can be an elbow-head impact or a head
      head impact. The authors believe that the low incidence of fractures, severity of
      the lesions, and discomfort caused by possible protective masks make their use
      unjustified. The data collected during this study witness that in soccer 21 of 34
      cases of maxillofacial fractures are caused by elbow-head impacts. This fact
      suggests a preventive strategy against violent behavior in soccer play. Because
      the use of any sort of helmet proved impossible, the introduction of more severe
      penalties and a greater respect for the rules of the game by the players could
      reduce the percentage of impacts during matches. Impacts cause the most serious
      and frequent lesions in the maxillofacial region.

PMID- 12218790
TI  - Removal of titanium plates coated with anodic titanium oxide ceramic:
      retrospective study.
AB  - Transformation of the surface of metallic titanium with titanium oxides prepared
      in various ways is a modern procedure. For more than 15 years, the authors have
      been utilizing fixing elements coated with titanium oxide ceramics, prepared by
      anodic oxidation and thermal treatment, for purposes of jawbone osteosynthesis.
      The aim of the authors' work was to assess the extent to which the titanium oxide
      ceramic coating influences the fate of the plates used for osteosynthesis within
      the human organism, in regard to the possible need for their removal. During a 5
      year period, 108 of 1,396 plates coated with anodic titanium oxide had to be
      removed for various reasons: plate exposure (47), osteomyelitis (25), palpable
      swelling and tenderness (21), patient request for psychological reasons (13), or
      fracture of the plate (2). In none of these 108 cases was metallosis observed,
      which otherwise is reported relatively frequently in the vicinity of traditional
      titanium fixing elements, nor was any tissue damage connected with the surface of
      the plates. The results indicate the favorable properties of the titanium oxide
      ceramic surface.

PMID- 12218791
TI  - Solitary fibrous tumor of the orbit.
AB  - Painless unilateral proptosis is a frequent manifestation of numerous orbital
      neoplastic and non-neoplastic processes. Various mesenchymal tumors of both
      fibrohistiocytic and vascular origin are well-described causes. Solitary fibrous
      tumors (SFTs) are rare spindle-cell neoplasms usually found associated with
      serosal surfaces, especially the pleura, but they have recently been described in
      a number of extrapleural sites including the orbit. The authors describe the case
      of an 18-year-old man who presented with a 6-month history of painless proptosis
      in the right eye. A visible nontender mass in the right supermedial orbit
      producing ptosis of the upper lid was present. Magnetic resonance imaging (MRI)
      showed a well-circumscribed soft tissue mass located above the right globe with
      no obvious invasion of adjacent orbital structures. Uneventful surgical excision
      through a right frontal-orbitotomy approach was performed. Histological
      evaluation showed a solid, highly vascular tumor mass composed of spindle cells
      arranged in short ill-defined fascicles. Intense immunohistochemistry staining
      for CD34 and B-cell lymphoma 2 (BCL-2) differentiated the lesion from the more
      common hemangiopericytoma. Though considered benign, local recurrence and
      extraorbital extension of orbital SFTs have been described. Malignant behavior,
      including distant metastases, has been documented in as many as 20% of pleural
      cases with mortality rates as high as 50%. The natural history of this tumor in
      the orbit is unclear. The authors report the 35th case of orbital solitary
      fibrous tumor and discuss the differential diagnosis, histopathology,
      radiological features, and clinical course.

PMID- 12218792
TI  - Maxillofacial traumas.
AB  - Craniofacial traumas often involve the orbital region. This report describes an
      unusual case of penetration of an object into the left upper oral vestibule up to
      the left medial-upper orbital wall. The object was an indicator switch. A
      multidisciplinary approach was necessary to make a correct diagnosis and to apply
      the best surgical treatment. The object was surgically removed, and rigid
      internal fixation was used to reconstruct the inferior and medial orbital walls.
      The aesthetic and functional results were good. One year later, the patient
      showed a slight enophthalmos with normal ocular motility.

PMID- 12218793
TI  - Craniofacial reconstruction with computer-generated HTR patient-matched implants:
      use in primary bony tumor excision.
AB  - The aim of this clinical series is to report the effectiveness and safety of
      using computer-generated alloplastic hard tissue replacement (HTR) implants for
      the reconstruction of large defects of the cranio-orbital region when combined
      with simultaneous bone tumor excision. Seven patients who had large nonmalignant
      bony lesions of the anterior cranial vault and orbit underwent simultaneous bony
      excision and reconstruction with preoperatively fabricated custom alloplastic
      implants. Preoperatively, a 3D computed tomography (CT) scan was obtained from
      which an anatomical model was fabricated. On the anatomical model, the predicted
      amount of bone excision was performed. The defect in the model was then used to
      create an alloplastic (HTR polymer) implant for reconstruction and surgical
      placement. At the time of surgery, the implant was secured into position with
      either metal or resorbable plates and screws. In cases where the frontal sinus
      was in proximity to the implant, it was either cranialized and covered with a
      pericranial flap or obliterated with hydroxyapatite cement. All computer
      generated implants required some modification intraoperatively due to a larger
      amount of bony excision than was preoperatively planned. This was accomplished by
      modifying the sterile back-up of the implant as an addition to the original
      implant or completing reconstruction of the bony defect with hydroxyapatite
      cement. All patients have healed uneventfully with a minimum of 1 year follow-up
      (average, 2.6 years). In all cases, excellent contours have been maintained and
      all patients have remained infection-free. In the management of large benign bony
      tumors of the cranio-orbital region, simultaneous reconstruction with custom
      implants fabricated from porous, hydrophilic HTR polymer can be preoperatively
      fabricated based on an estimate of the subsequent bony defect. The successful use
      of this approach depends on a favorable tissue quality of the recipient site, a
      generous preoperative estimate of the amount of bone that will be resected so
      that the implant is adequate, intraoperative techniques of expanding the implant
      reconstruction, and intraoperative methods to assure a partitioning of the
      implant from the frontal sinus.

PMID- 12218795
TI  - Study of asymmetries of the cranial vault in plagiocephaly.
AB  - Organic plagiocephaly is caused by premature synostosis of the coronal suture.
      The subject is dealt with in the context of a desire to categorize these types of
      asymmetries and to find asymmetry indices using computed tomography scan images.
      From a cephalometric point of view, the authors looked for a reproducible
      reference, independent of the structures to be studied-the vestibular
      orientation, which is based on the definition of a mediolabyrinthic plane, making
      it possible to assess the symmetry. One of the problems encountered in this study
      of the cranial vault is related to the difficulty of determining reproducible
      cranial indicators. Consequently, the authors propose an alternative method for
      studying the asymmetry using the tracing, measurement of radiuses, and the ratio
      between symmetrical radiuses from the origin of the vestibular indicator. When it
      came to putting this tool into practice, the authors opted to design a customized
      instrument. The tool was then applied to dry skulls considered to be symmetrical
      and to a few cases of plagiocephaly before and after surgery. The study of dry
      skulls, used as a reference, demonstrates the general shape of the curve
      representative of the symmetry evolution over the entire vault in healthy models.
      Analysis of pathological cases reveals the asymmetry of the cranial profiles (for
      example, homolateral frontal flattening, contralateral frontal prominence). It
      also makes it possible to assess the anterior, posterior, low, or high location
      of asymmetries of the vault. This analysis enables quantitative assessment of
      asymmetries using ratios, along with objective evaluation of postoperative
      results, with demonstration of surgical improvements and overcorrections. This
      analysis could make it possible to characterize asymmetries according to their
      shape. An attempted quantitative classification system for plagiocephalies
      according to four degrees of severity is proposed. The proposed analysis permits
      an objective, reproducible, and quantitative method for studying cranial vault
      asymmetries. A study on a larger population would make it possible to confirm
      these hypotheses and put forward new ones. Prospects for development could relate
      to study of all asymmetry problems affecting the base of the skull and the face.

PMID- 12218794
TI  - Cancellous bone grafting in alveolar cleft repair: new experience.
AB  - Bone grafting plays an important role in the dental rehabilitation of patients
      with alveolar cleft. During the period between 1993 and 2001, 12 patients with
      alveolar clefts have been treated in our clinic. Cancellous iliac bone grafts
      were used in all 12 patients. Seven patients had left and five patients had right
      complete unilateral cleft lip and complete cleft palate operations. All patients
      had palatal fistulas. The ages were between 4 and 18 years (mean age, 10.5 y).
      Seven of them were female (58.4%) and 5 were male (41.6%). All the cancellous
      grafts survived. Enough filling and the closure of the fistulas were achieved
      except one patient who had wound dehiscence and partial graft loss. The patients
      experienced a limp for 2 days (mean time) because of the donor site. This
      surgical procedure achieves successful results if it is used with the proper
      indication in suitable cases.

PMID- 12218796
TI  - A case of synovial chondromatosis of the TMJ: treatment based on stage of the
      disease.
AB  - A patient with synovial chondromatosis of the temporomandibular joint extending
      to the preauricular skin, parotid, and infratemporal fossa was operated and
      followed with a stable remnant, for 2 years postoperatively. In light of
      literature and what the authors have learned from this case, the authors
      emphasize stage of the disease as a risk factor for recurrence. The long history
      of symptoms, calcified and conglomerated radiological appearance of the lesion,
      and extensive involvement of the joint and periarticular area of this case
      indicate a late-stage disease in which the metaplastic activity dwindles. For
      late stages, the authors suggest a conservative approach that will only provide
      symptom relief and prevent secondary joint deformity to avoid potential
      complications and morbidities of a more extensive surgery.

PMID- 12218797
TI  - Clinical findings precede objective diagnostic testing in the identification of
      increased ICP in syndromic craniosynostosis.
AB  - Crouzon syndrome is an autosomal dominant disorder resulting in facial
      dysmorphism and craniosynostosis involving multiple cranial sutures. A common but
      often unrecognized early complication associated with craniosynostosis is a
      finding of increased intracranial pressure (ICP). This increase in ICP can lead
      to optic atrophy, neuronal damage, and mental deficits. The case of a 21-month
      old girl with Crouzon syndrome is described. Although the child was clinically
      asymptomatic, a routine ophthalmic exam revealed papilledema and subsequently
      increased intracranial pressure and craniosynostosis were found. Cranial
      expansion and bicanthal advancement were performed to relieve the increased
      pressure. In cases such as these, long-term follow-up is essential because of the
      progressive nature of the disorder as well as the possibility of a recurrence of
      elevated intracranial pressure and a need for secondary decompressive surgery.

PMID- 12218798
TI  - Compartmentalized bone regeneration of cranial defects with biodegradable
      barriers--effects of calcium sodium phosphate surface coatings on LactoSorb.
AB  - In bony defects of the cranium, bone healing may be complicated by prolapse of
      surrounding tissue into the defect. This tissue acts as a potential obstruction
      to the migration of osteogenic cells, resulting in impaired bone formation. It
      has been shown in previous studies that when a membrane composed of resorbable
      polymers (LactoSorb) is placed over a cranial bone defect, it inhibits connective
      tissue from entering the wound and improves the rate and quality of the bony
      regenerate. This study is an extension of this work and specifically evaluated
      the effects of differing calcium-based surface coatings on membrane-covered
      cranial defects in the rabbit model. In non-critical size, full-thickness defects
      of the mature rabbit calvarium, four differently treated LactoSorb membranes were
      evaluated in each animal model over a 1-year postoperative period. The surface
      coatings (three treated, one untreated) consisted of a base-powdered material of
      calcium sodium phosphate (Osteostim, EBI, NJ), which were applied by different
      methods (pressed, brushed, one-sided versus two-sided). Evaluation consisted of
      cross-sectional histologic assessment of the cranial detects determining the
      quantitative bony fill and the presence of residual polymer material and calcium
      sodium phosphate. This study produced the following findings: (1) cranial defect
      regeneration occurs faster with calcium-coated membranes and is complete by 3
      months; (2) no difference could be seen between the different methods of calcium
      sodium phosphate coating; (3) the calcium sodium phosphate coatings did not
      inhibit resorption of the biodegradable membranes for those systems that had
      coatings on one side; however, systems completely covered showed delayed
      resorption; and (4) the calcium sodium phosphate coatings did not produce any
      inflammatory reactions. These findings suggest that, in addition to inhibiting
      connective tissue from entering the wound site, the calcium coatings on
      resorbable devices may have beneficial effects in selected clinical conditions,
      especially in conditions where faster bone regeneration is necessary.

PMID- 12218799
TI  - Assessment of facial tissue expansion with three-dimensional digitizer scanning.
AB  - This article reports a three-dimensional (3D) digital color scanning system used
      in the measurement of facial soft tissue expansion. This system consists of
      digital scanning equipment, software for stereolithographical (STL) forms and
      nonuniform rational B-spline (NURBS) surfaces, and a computer-aided design
      program. Accurate data for the area of scar excision and the expanded
      cervicofacial flap were obtained by using this measuring system in a young
      patient with scar contracture of the face. This technique can accurately model
      the reconstruction and make plastic surgery planning a truly interactive
      procedure.

PMID- 12218800
TI  - Use of new bioabsorbable tacks and a tackshooter in cranial bone osteofixation
      saves operative time.
AB  - A new device (a tackshooter) to apply bioabsorbable tacks in craniofacial surgery
      has been developed. This new device was used in 15 children who underwent various
      cranioplasty procedures to demonstrate its reliability and simple technical
      application in cranial bone osteofixation. Bone segments were fixed together and
      to the cranial bones using Biosorb plates and tacks. Stable and secure fixation
      was obtained intraoperatively, with reduced operative time (10-15%) compared with
      earlier use of plates and screws. However, its use in very thin bone (<1 mm
      thick) is very limited because of bone fragility. In conclusion, use of tacks and
      a tackshooter reduces operative time, risk of infection and blood loss, and
      consequently costs. It is therefore very useful in selected craniofacial cases.

PMID- 12218801
TI  - Frontocranial remodeling without opening of frontal sinuses in a scaphocephalic
      adolescent: a case report.
AB  - The skull deformities of scaphocephalic patients who have not had surgery are
      very disturbing for them, even when they are moderate. They are usually more
      preoccupied by the frontal narrowing and elevation than by the occipital bulge. A
      midline splitting of the anterior cranium enables solving these problems, and the
      preservation of the frontonasal sinuses by cutting above them significantly
      diminishes the infectious risk. The case of a 19-year-old young man, followed
      since childhood, who finally requested the correction, is presented and
      discussed.

PMID- 12218802
TI  - Scalping forehead flap for extranasal reconstructions: total reconstruction of
      the lower lid.
AB  - J. M. Converse described the scalping forehead flap in 1942 with the aim of using
      it in total nasal reconstruction. A rich net of arterial and venous vessels
      constitute the basic pattern of its blood supply through three principal
      pedicles: (1) temporal superficial, (2) supraorbital, and (3) supratrochlear. It
      was described for nasal reconstruction, but due to its characteristics, such as
      color of the frontal skin, texture, hairless skin, and reliable irrigation, it
      can be used in the reconstruction of other facial areas. According to these
      particularities, the Converse flap was used in the reconstruction of a total left
      lower lid and adjacent lateral nose and cheek areas in a patient with an extended
      squamous carcinoma. The tumoral resection included the removal of (1) complete
      lower lid, (2) lacrimal lower canaliculus, sac, and nasolacrimal duct, (3) lower
      ocular conjunctiva, (4) intraorbitary fat and both inferior oblique and inferior
      rectus muscles, and (5) adjacent skin of the nose and cheek. Postoperative
      controls showed an excellent aesthetic and functional result. A hypochromic
      frontal skin graft was the only sequela; definitive skin coloration was obtained
      by a dermopigmentation technique. The versatility of this forehead flap allows it
      to be successfully used for reconstruction not only in the nasal area but also in
      other facial ones.

PMID- 12218803
TI  - Treatment of condyle fracture caused by mandibular angle ostectomy.
AB  - A prominent mandibular angle is considered to be unattractive in Asian countries
      because it gives the face a square and muscular appearance. Successful correction
      by angle ostectomy has been reported, but one of the serious complications of
      angle reduction ostectomy is fracture of the mandibular condyle. If the ostectomy
      line is misdirected vertically, the condyle may be fractured. The authors
      experienced two cases of condylar fracture during angle reduction. Case 1 was a
      pulled-out condylar fracture, where an L-shaped miniplate was then attached by
      external approach, and intermaxillary fixation (IMF) with arch bar was used on
      postoperative day 14. With release of the IMF, a systematic approach for a jaw
      opening exercise was begun. On postoperative day 21, the elastics were placed to
      assist in guiding protrusion of the mandible anteriorly 24 hours a day. After
      postoperative day 28, it was possible to completely abandon daytime elastic
      fixation. The exercise was modified to lateral movement. Case 2 was green-stick
      condylar fracture, with the IMF with arch bar applied on postoperative day 10.
      After releasing the IMF, the exercise involved the daily use of several tongue
      blades, and range of motion increased by wedging additional blades until
      postoperative day 21. More aggressive stretching was continued with 22 blades on
      postoperative day 28. On the removal of the arch bar, the occlusion was stable
      and followed by more aggressive stretching and physical therapy. Both cases were
      successfully restored and had good results. The authors believe the exercise
      protocols and algorithms they used may serve as a standard procedure of treatment
      in condylar fracture caused by angle ostectomy.

PMID- 12218804
TI  - Expression of heat shock protein 27 (HSP27) in human temporomandibular joint
      discs of patients with internal derangement.
AB  - Heat shock proteins (HSPs) are believed to represent a cellular stress response
      mechanism that protects intracellular proteins from damaging events. Some studies
      have demonstrated an enhanced expression of large-molecular-weight HSPs in
      diseased systematic joints. Small heat shock proteins, and among these HSP27,
      have been studied to a lesser extent. HSP27 has cytoprotective and biosynthetic
      functions within chondrocytes, and it is an estrogen-associated protein that is
      under hormonal modulation. To improve understanding at a molecular level of the
      pathophysiology of certain temporomandibular joint disorders, the authors carried
      out this immunohistochemical study to assess the presence of HSP27 in human TMJ
      discs. Twelve adult human TMJ discs (10 diseased and 2 healthy discs) and 5 TMJ
      fetal human discs were used in this study. Adult discs and TMJ tissues of human
      fetuses were fixed in 10% buffered formalin. Samples were then processed for
      histologic examination. Sections were immunohistochemically stained using the
      streptavidin-biotin detection method. No reaction product for HSP27 in the discs
      of fetuses was noted. HSP27 was weakly expressed in normal TMJ discs and highly
      up-regulated in discs of patients showing new vessel formation and chondroid
      metaplasia. Any correlation between gender and HSP27 was found in the sample,
      being the up-regulation of HSP27 related mostly to major histopathological
      changes. This different pattern of HSP27 immunostaining in human TMJ discs
      detected in the authors' specimens suggests that the expression of this small HSP
      is functionally modulated. In fact HSP27 up-regulates in internal derangement
      specimens with major histopathological changes; on the other hand, it is not
      expressed or only weakly expressed in TMJ discs of fetuses and normal TMJ discs.

PMID- 12218805
TI  - Masks depicting hemifacial microsomia and cleft lip.
AB  - All masks are created by craftspeople. Accordingly, most masks are generally
      predictable in dimensions, and the portraitures usually depict the faces and
      heads of humans. The authors found some masks representing the features of
      craniofacial anomalies, such as hemifacial microsomia and, rarely, cleft lip.
      Reviewing the legends of wearing masks with a medley of grotesque features, the
      authors could deduce the tone of society in those days. A mask, "crooked mouth,"
      of Native Americans shows typical lineament of hemifacial microsomia. The
      deformity of the face was legendarily regarded as resulting from trauma caused by
      either "one's fault" or a "curse of God." "Yangban" (noblemen of aristocratic
      class) customarily wore the cleft lip mask in age-old Korean masquerade revels.
      Laymen ridiculed Yangban by making cleft lip masks for them. The authors presume
      that the victims of craniofacial deformities were treated contemptuously at that
      time.

PMID- 12218807
TI  - Findings at helical CT-enteroclysis in symptomatic patients with crohn disease:
      correlation with endoscopic and surgical findings.
AB  - PURPOSE: The purpose of our study was to assess the diagnostic potential of
      helical CT-enteroclysis (HCTE) and to correlate our findings to endoscopic and
      surgical results. METHODS: Twenty-eight consecutive patients suffering from
      histologic proven Crohn disease underwent HCTE and endoscopy within 4 weeks. HCTE
      findings were read by two observers in consensus and compared with endoscopic and
      surgical results. RESULTS: Morphological signs of an acute or recurrent bowel
      inflammation were found in 25 of 28 (89%) patients. HCTE demonstrated accurately
      all mural and extramural changes of the inflamed bowel walls. Moreover, in 18 of
      25 (72%) patients, HCTE depicted additional pathologic changes such as fistulas,
      abscesses, and skip lesions, all of which could not be visualized by endoscopy.
      CONCLUSION: HCTE is an accurate technique to detect mural and extramural
      abnormalities in patients with Crohn disease. HCTE should be considered as a
      complementary imaging method to endoscopy, and should be the first imaging method
      especially when Crohn-associated complications are suspected.

PMID- 12218808
TI  - Automated knowledge-guided segmentation of colonic walls for computerized
      detection of polyps in CT colonography.
AB  - PURPOSE: We have developed a novel automated technique for segmenting colonic
      walls for the application of computer-aided polyp detection in CT colonography.
      In particular, the technique was designed to minimize the presence of
      extracolonic components, such as small bowel, in the segmented colon. METHODS:
      The segmentation technique combines an improved version of our previously
      reported anatomy-oriented colon segmentation technique with a colon-based
      analysis step that performs self-adjusting volume-growing within the colonic
      lumen. Extracolonic components are eliminated by intersecting of the resulting
      two segmentations, so that the colonic walls remain in the intersection. The
      technique was evaluated on 88 CT colonography datasets. The colon segmentations
      were evaluated subjectively by four radiologists, as well as objectively by
      performance of an automated polyp detection on the segmentation. For comparison,
      the tests were also performed for the anatomy-oriented colon segmentation
      technique. RESULTS: On average, the technique covered 98% of the visible colonic
      walls. Approximately 50% of the extracolonic components remaining in the anatomy
      oriented segmentation were removed, but 10-15% of the segmentation still
      contained extracolonic components. The dataset-based false-positive rate of the
      automated polyp detection was improved by 10% without compromising the 100% case
      based sensitivity, and the case-based false-positive rate was improved by 15%
      over the previous false-positive rate. CONCLUSIONS: The technique segments
      practically all of the colonic walls in the region of diagnostic quality with a
      large reduction in the amount of extracolonic components over our previously used
      technique. The new segmentation improves the specificity of our computer-aided
      polyp detection scheme significantly without any degradation in detection
      sensitivity.

PMID- 12218809
TI  - Small-bowel wall thickening related to a long intestinal tube: incidental CT
      finding mimicking a pathologic condition.
AB  - PURPOSE: The purpose of this work is to describe the CT findings of small-bowel
      wall thickening related to a long intestinal tube in patients with bowel
      obstruction and to discuss the mechanism of this incidental finding. METHOD: Ten
      consecutive patients with intubation of a long intestinal tube for bowel
      obstruction were studied retrospectively. Five cases were diagnosed as colon
      cancer, three as postoperative adhesion, one as Meckel diverticulitis, and one as
      internal hernia of the small bowel. The history and imaging studies of these
      patients were reviewed. RESULTS: Small-bowel wall thickening was demonstrated in
      6 of the 10 patients on CT. All findings of small-bowel wall thickening were
      observed along the long intestinal tube. Multiple accordion-shaped pleats were
      seen in five patients on longitudinal sections of the small bowel. CONCLUSION:
      Although definitive pathologic proof is lacking, small-bowel wall thickening
      related to a long intestinal tube was thought to represent a multiply "pleated"
      normal small bowel along a long intestinal tube.

PMID- 12218810
TI  - H(2) (15)0 positron emission tomography validation of semiquantitative prostate
      blood flow determined by double-echo dynamic MRI: a preliminary study.
AB  - PURPOSE: Information regarding prostate blood flow as determined by positron
      emission tomography (PET) with H 0 may provide useful information about tumor
      diagnosis; however, PET requires a cyclotron for the production of an extremely
      short half-life (2 minutes) tracer. Therefore, the aim of this study was to
      propose a complementary index for blood flow as determined by MRI to validate the
      results and compare them with PET, especially for prostate tissue. METHODS: Six
      consecutive patients with prostate disease were studied. The two semiquantitative
      indices for tumor blood flow were calculated from the time-concentration curve
      measured from double-echo MR images. The theory of nondiffusible tracers by means
      of indicator dilution theory was applied to MR data. The relative regional blood
      flow (rrBF) was calculated as the ratio of the relative regional blood volume to
      relative regional mean transit time. Another proposed index was the maximum
      height of the time-concentration curve. PET studies were also performed, and
      absolute blood flow values were calculated for each subject. These indices
      calculated from different modalities were then compared. RESULTS: A significant
      correlation was found between the rrBF and the absolute blood flow as determined
      by PET (r = 0.69, p < 0.005). A significant correlation was also found between
      the maximum height of the time-concentration curve and the absolute blood flow (r
      = 0.85, p < 0.0001). CONCLUSIONS: The semiquantitative tumor blood flow indices
      measured with MRI have a good correlation with the corresponding measurements by
      PET; therefore, these indices may provide useful information about tumor
      diagnosis in clinical settings.

PMID- 12218812
TI  - Subcutaneous nodules at the injection site of low-molecular-weight heparin: a
      mimic of metastatic disease at CT.
AB  - PURPOSE: To describe the appearance and prevalence of subcutaneous nodules in the
      anterior abdominal wall seen at CT in cancer patients receiving subcutaneous
      injections of low-molecular-weight heparin (LMWH). METHODS: CT examinations were
      reviewed in 426 patients receiving subcutaneous abdominal wall injections of LMWH
      for the presence of nodules. Nodules were evaluated for contour, maximal
      diameter, CT attenuation, and presence of hazy changes or air in the surrounding
      fat. RESULTS: Fourteen (3%) of the 426 patients had nodules attributable to
      subcutaneous injections of LMWH. Findings included poorly defined borders (100%),
      adjacent hazy soft tissue changes (100%), adjacent air (57%), and a mean CT
      attenuation of -4.4 HU (range: -50-40 HU). Three (0.7%) of 426 patients had
      nodules caused by metastatic disease. One (33%) nodule had poorly defined
      borders, two (67%) had surrounding hazy changes, one (33%) had air in adjacent
      tissue, and there was a mean CT attenuation of 44 HU (range: 14-140 HU). One
      (0.2%) patient had a subcutaneous nodule of uncertain etiology. CONCLUSION:
      Patients receiving subcutaneous injections of LMWH may develop nodules at the
      injection sites. Such nodules can resemble metastatic tumor deposits at CT, and
      careful correlation with clinical history and growth trends of metastatic
      deposits elsewhere in the patient is needed to avoid misdiagnosis.

PMID- 12218811
TI  - Multislice CT angiography through an implantable catheter and port system: early
      experience in detection of vascular complications during hepatic arterial
      infusion chemotherapy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the use of multislice CT in
      the evaluation of vascular patency in patients during hepatic arterial infusion
      chemotherapy of liver tumors. MATERIALS AND METHODS: Thirty-three patients were
      prospectively examined by CT angiography through the indwelling catheter and port
      system. Visibility of hepatic arteries and vascular patency were graded 0 to 3
      and were compared with digital subtraction angiography (DSA). RESULTS: Average
      visualization scores of CT angiography and DSA were 1.7 and 2.5, respectively, in
      common hepatic artery (CHA) and proper hepatic artery (PHA), 2.5 and 2.3 in right
      hepatic artery (RHA), 2.6 and 2.6 in left hepatic artery (LHA), 2.3 and 2.2 in
      segmental RHA, and 2.1 and 2.0 in segmental LHA. Stenoses were found in proximal
      hepatic arteries in 9 on CT angiography and 13 on DSA. Stenoses were found in
      branches of the hepatic artery in 21 on CT angiography and 16 on DSA. CONCLUSION:
      The authors' results indicate that multislice CT angiography of the hepatic
      arteries is equivalent to DSA and may demonstrate vascular complications of
      hepatic arterial infusion chemotherapy.

PMID- 12218813
TI  - Asymptomatic diaphragmatic hiatal herniation of the pancreas.
AB  - Herniation of the pancreas into a diaphragmatic hiatal hernia is a rare condition
      reported in only three cases; all were symptomatic. We present a CT diagnosis of
      hiatal hernia containing the body and tail of a normal pancreas in an
      asymptomatic patient.

PMID- 12218814
TI  - Cross-sectional imaging findings in congenital intestinal lymphangiectasia.
AB  - A 37-year-old woman presented with an 18 month history of recurrent severe
      abdominal pain, recurrent diarrhea since her second year of life, and mild
      peripheral edema. CT and more clearly MRI revealed signs of small bowel and
      mesenterial edema with partial tubular appearance, which correlated well with the
      histopathologic findings shown in duodenal biopsy. This is the first report of MR
      findings in congenital intestinal lymphangiectasia with correlation with other
      imaging modalities.

PMID- 12218815
TI  - Small bowel obstruction caused by snail's shell: radiographic and CT findings.
AB  - We report a case of small bowel obstruction in a 74-year-old woman presenting
      with abdominal pain due to the accidental swallowing of a snail shell. A
      diagnosis of obstruction was made by abdominal radiograph, and its etiology was
      found after abdominal CT was performed. This is an unusual case of small bowel
      obstruction due to a foreign body that was preoperatively diagnosed with imaging.

PMID- 12218816
TI  - MR imaging of mullerian mucinous borderline tumors arising from endometriotic
      cysts.
AB  - This report describes MR findings of mullerian mucinous borderline tumors,
      pathologically proven to have arisen from endometriotic cysts, in three patients.
      They were unilocular or paucilocular masses with mural nodules. Cystic components
      showed hyperintensity on both T1- and T2-weighted images, simulating clear cell
      or endometrioid carcinomas arising from endometriotic cysts. Mural nodules showed
      prominent high signal intensity on T2-weighted images. Correlation with
      pathologic findings suggests that this hyperintensity reflects intraluminal
      mucinous material and stromal edema.

PMID- 12218817
TI  - MR imaging findings in fetal goiter caused by maternal graves disease.
AB  - Antenatal diagnosis of fetal goiter should be appropriately managed to avoid
      perinatal complications. Here, we present the MR imaging features of a fetal
      goiter caused by maternal Graves disease. Diffusely enlarged fetal thyroid gland
      was seen showing homogeneously elevated signal on T1-weighted images and
      intermediate signal on T2-weighted images. To our knowledge, this is the first MR
      imaging documentation of fetal goiter.

PMID- 12218818
TI  - MRI for evaluating congenital bile duct abnormalities.
AB  - Congenital bile duct diseases consist of ductal plate development abnormalities
      and are genetically determined. These biliary abnormalities are encountered
      mainly in congenital fibrocystic diseases, represented by congenital hepatic
      fibrosis and different forms of Caroli disease. On the other hand, polycystic
      hepatic diseases also present cystic abnormalities, which could be confused with
      biliary dilatations, especially in the perihilar area. Further, intricate forms
      between Caroli and polycystic hepatic diseases are possible. In congenital bile
      duct paucity, which is extremely rare, the biliary tree, located on the opposite,
      is not visible. MRI modalities for the analysis of the biliary tree are mainly
      represented by T -weighted sequence, also known as MR cholangiography (MRCP), and
      T gadolinium-enhanced sequences. Familiarity with the most common appearances of
      congenital bile duct dilations, its variants, and related complex diseases
      facilitates accurate diagnosis and allows and helps avoid misinterpretation.

PMID- 12218819
TI  - Intrapulmonary lymph nodes: thin-section CT features of 19 nodules.
AB  - PURPOSE: The purpose of this study was to describe the thin-section CT features
      of intrapulmonary lymph nodes that accompanied primary or metastatic lung tumors.
      METHOD: A retrospective analysis of thin-section CT features was performed on 19
      nodules in 16 patients with pathologically confirmed intrapulmonary lymph nodes
      that accompanied primary or metastatic lung tumors. RESULTS: Of the 16 patients,
      13 had a solitary nodule and 3 had two nodules. All nodules were distributed in
      the middle lobe, lingula, or lower lobe. On thin-section CT images, the nodule
      was located abutting the visceral pleura (n = 10) or within 8 mm of the visceral
      pleura (n = 9). The thin-section CT findings showed that most of the nodules were
      well circumscribed (n = 18), homogeneous (n = 19), ovoid (n = 10), or round (n =
      9) and smaller than 12 mm in maximal diameter. The surrounding lung field was
      normal (n = 16). CONCLUSION: Intrapulmonary lymph nodes are subpleural in the
      lower lung field. On thin-section CT, they are well circumscribed, homogeneous,
      round or ovoid, and smaller than 12 mm in maximal diameter. In the differential
      diagnosis of subpleural nodules located in the lower lung field, it should be
      kept in mind that they may be intrapulmonary lymph nodes even though the patient
      has malignancy.

PMID- 12218820
TI  - Primary malignant fibrous histiocytoma of the chest wall: CT and MR appearance.
AB  - PURPOSE: The purpose of this work is to describe the CT and MR appearance of
      primary malignant fibrous histiocytoma (MFH) of the chest wall. METHOD: Eleven
      men and eight women (45-76 years old) with primary MFH of the chest wall who
      underwent both CT and MRI were enrolled, and the imaging interpretation was
      retrospectively compared to the pathologic specimen. RESULTS: All tumors were
      inhomogeneous in appearance on CT scans. All tumors showed high signal intensity
      on T2-weighted images. On T1-weighted MR images, tumors displayed inhomogeneous
      isosignal intensity in 15 cases (79%) and low signal intensity in 5 (21%)
      compared with the surrounding muscle. Tumors exhibited inhomogeneous enhancement
      in all except three localized tumors on enhanced CT and MRI. Invasion of
      intercostal muscle was noted on MR images in 18 patients (95%) and on CT in 11
      patients (58%). CONCLUSION: There might be various radiologic appearances of MFH.
      However, CT and MRI are able to demonstrate the exact localization and disease
      extent of MFH arising in the chest wall.

PMID- 12218821
TI  - Benign tracheobronchial stenoses: changes in short-term and long-term pulmonary
      function testing after expandable metallic stent placement.
AB  - PURPOSE: To determine the short- and long-term improvement in airflow dynamics in
      patients undergoing tracheobronchial stent placement for benign airway stenoses.
      METHODS: Twenty-two patients underwent 34 tracheal and/or bronchial stent
      placement procedures for benign airway stenoses and had the results of pulmonary
      function tests available. Stent placement indications included bronchomalacia
      after lung transplantation (n = 11), postintubation stenoses (n = 6), relapsing
      polychondritis (n = 2), and 1 each of tracheomalacia, tracheal compression, and
      histoplasmosis. Six patients underwent more than one stent placement procedure
      (range: 2-7 procedures). The mean forced expiratory volume in one second (FEV(1)
      ), forced expiratory flow rate in the midportion of the forced vital capacity
      curve (FEF(25-75) ), forced vital capacity, and peak flow (PF) rate obtained
      before stent placement were compared with those immediately after stent placement
      and with those measurements most remote from stent placement using the paired two
      tailed test. RESULTS: All patients reported improved respiratory function
      immediately after stent placement. The mean FEV(1), FEF(25-75), and PF rate
      improved significantly (p < 0.001, p = 0.002, and p = 0.009, respectively) after
      stent placement. On long-term follow-up averaging 15 months after stent
      placement, these parameters declined despite patients' subjective sense of
      improvement. Segregating the population into transplant and nontransplant airway
      stenosis etiologies, however, FEF(25-75) and PF rate remained significantly
      improved (p = 0.045, p = 0.027, respectively), over the long term for the latter.
      FEV increased after subsequent stent placements for patients receiving multiple
      stents. CONCLUSION: Stent placement for benign tracheobronchial stenoses provides
      significant immediate improvement in airflow dynamics. Long-term improvement in
      airflow obstruction may be expected, and additional stent placements may further
      improve pulmonary function.

PMID- 12218822
TI  - Fractal analysis of small peripheral pulmonary nodules in thin-section CT:
      evaluation of the lung-nodule interfaces.
AB  - OBJECTIVES: To analyze the lung-nodule interfaces on small peripheral pulmonary
      nodules (<2 cm) in thin-section CT (HRCT) images with fractal analysis. METHODS:
      Thin-section CT images from 70 patients with bronchogenic carcinomas (61
      adenocarcinomas and 9 squamous cell carcinomas) and 47 patients with benign
      pulmonary nodules (23 hamartomas, 13 organizing pneumonias, and 11 tuberculomas)
      were used. For calculation of fractal dimensions (FDs), the authors used a box
      counting method for binary- and gray-scale images of nodules. FD(two-dimensional
      [2D]) was an FD obtained from the binary image, and FD(three-dimensional [3D])
      was an FD obtained from the gray-scale image. RESULTS: The FD(2D)s of hamartomas
      were smaller than those of other nodules ( < 0.05). The FD(3D)s obtained from the
      gray-scale images of organizing pneumonias and tuberculomas were greater than
      those of bronchogenic carcinomas ( < 0.0001) and hamartomas ( < 0.0001). In
      bronchogenic carcinomas, FD(3D)s of adenocarcinomas were greater than those of
      squamous cell carcinomas ( < 0.05). CONCLUSIONS: Fractal dimensions reflect the
      characteristics of the lung-nodule interfaces of small peripheral pulmonary
      nodules. The FD(2D)s revealed the irregularities of the contours. On the other
      hand, FD(3D)s revealed the complexities of the heterogeneous textures. With use
      of FD(2D) and FD(3D), it may be possible to distinguish bronchogenic carcinomas
      from benign pulmonary nodules. Moreover, FD(3D) may make it possible to
      distinguish between adenocarcinomas and squamous cell carcinomas.

PMID- 12218823
TI  - Desmoplastic small round cell tumor: imaging findings associated with
      clinicopathologic features.
AB  - PURPOSE: To describe imaging findings of desmoplastic small round cell tumor
      (DSCRT) and to clarify the relation between radiologic appearances and
      clinicopathologic features. MATERIALS AND METHODS: CT scans and MRI examinations
      of four male patients with histologically confirmed DSCRT (mean age = 20 years)
      were retrospectively analyzed. RESULTS: The common imaging finding was multiple
      peritoneal masses with regular contour situated within mesentery. Tumors showed
      central low attenuation in 75% of patients on nonenhanced CT. All tumors showed
      inhomogeneous enhancement on CT. Small foci of punctate calcification were
      identified in a part of the tumor in all patients. Bone metastases were
      identified on enhanced CT in two patients 2 and 8 months after diagnosis,
      respectively. Pleural dissemination was identified in all patients, and one
      patient had double-sided dissemination. T2-weighted MRI showed inhomogeneous high
      signal intensity, and small cysts were identified in two patients. Fluid-fluid
      levels were identified in six tumors on T2-weighted images, which suggested the
      presence of hemorrhage. Tumors had inhomogeneous signal intensity low or
      isointense relative to skeletal muscle on T1-weighted images. Two lesions
      exhibited inhomogeneous enhancement with central low intensity consistent with
      necrosis. CONCLUSION: Imaging studies can depict disseminated characteristics and
      disease extent during the clinical course of DSRCT.

PMID- 12218824
TI  - Double-ring esophageal sign: pathognomonic for esophageal lipomatosis.
AB  - The peculiar appearance of the proximal esophagus on CT attributed to esophageal
      lipomatosis is not well recognized. We have recently encountered seven cases from
      over a period of 2 months and report them to reach a broader audience of
      radiologists who may be unaware of its existence. Its typical CT features should
      lead to the correct diagnosis and be differentiated from other fatty lesions
      known to involve the esophagus, namely, lipoma and liposarcoma.

PMID- 12218825
TI  - Role of helical CT in detecting right ventricular dysfunction secondary to acute
      pulmonary embolism.
AB  - OBJECTIVE: The purpose of this study was to evaluate the role of helical CT in
      detecting right ventricular dysfunction (RVD) after acute pulmonary embolism
      (PE). METHODS: This was a retrospective study consisting of 25 patients with CT
      scans positive for acute pulmonary embolism who had either follow-up
      echocardiography (23 patients) or pulmonary angiography (2 patients). CT scans
      were reviewed for findings suggestive of RVD. Scans were considered positive for
      RVD if the right ventricle (RV) was dilated or if the interventricular septum was
      deviated towards the left ventricle. Results were then correlated with the
      results of echocardiography or pulmonary angiography to estimate the sensitivity
      and specificity of CT in detecting RVD associated with PE. RESULTS: Within this
      group of 25 patients with PE, CT demonstrated sensitivity of 78% (7/9),
      specificity of 100% (16/16), and positive predictive value of 100% (7/7) in
      detection of RVD. CONCLUSION: CT may be useful in detecting RVD in patients with
      acute PE.

PMID- 12218826
TI  - Electron beam tomography imaging of coronary calcium: the effect of body mass
      index on radiologic noise.
AB  - PURPOSE: To measure selected parameters of radiologic noise in electron beam
      tomographic (EBT) images obtained for coronary artery calcium (CAC) screening,
      and to determine an association between the level of radiologic noise and patient
      body mass index (BMI). METHODS: Electron beam tomographic CAC studies were
      performed on 311 persons. The study sample was stratified into three groups
      according to subjects' BMI. Three regions of interest (ROI) parameters of
      radiologic noise were used to measure the strength of association between the
      level of radiologic noise and BMI. RESULTS: The measured ROI parameters of
      radiologic noise demonstrated a significant difference across the strata, with
      values gradually increasing from the normal weight group to the obese group. All
      ROI parameters showed significant correlations with BMI. CONCLUSION: These
      findings support proposals to modify the current EBT CAC scoring methodology to
      account for variability in patient body size. These modifications may reduce the
      image noise levels and subsequently decrease the number of false-positive
      results.

PMID- 12218827
TI  - Parameters affecting bolus geometry in CTA: a review.
AB  - CT angiography (CTA) is based on acquisition of data during the arterial phase of
      contrast material passage. CTA needs timing of the contrast bolus, which should
      be based on accurate knowledge of bolus geometry. Experimental and human studies
      on bolus geometry and bolus timing in CTA were reviewed. Important parameters of
      bolus geometry and methods of bolus timing (test bolus and bolus tracking) are
      described. Recommendations are given for an optimal CTA protocol.

PMID- 12218828
TI  - Pulmonary arterial aneurysms in primary antiphospholipid antibody syndrome.
AB  - A 20-year-old man with rapid refractory pulmonary infiltrates, fever, and chill
      was admitted to our hospital. Microscopic examination showed focal necrosis of
      the lung tissue, arterial thromboembolism, and alveolar hemorrhage. He tested
      positive for anticardiolipin IgG antibodies. Because of the absence of underlying
      diseases, the possibility of secondary antiphospholipid antibody syndrome was
      excluded. Follow-up chest CT after 2 years revealed pulmonary arterial aneurysms
      with diffuse ground-glass opacities. The aneurysms were occluded by coil
      embolization.

PMID- 12218829
TI  - Intramural hematoma of the ascending aorta secondary to descending thoracic
      aortic penetrating ulcer: findings in two patients.
AB  - The authors describe two cases of penetrating ulcers of the descending thoracic
      aorta associated with intramural hematoma of the ascending aorta. Since neither
      patient had evidence of diffuse thoracic aortic atherosclerosis to limit
      longitudinal extent of spread, it is postulated that the intramural hematoma
      started at the level of the penetrating ulcer and extended into the ascending
      aorta in a retrograde fashion. This is a potentially lethal entity, not
      previously described, for which the optimal clinical management is unknown.

PMID- 12218830
TI  - Fluid collections in the osseous tunnel during the first year after anterior
      cruciate ligament repair using an autologous hamstring graft: natural history and
      clinical correlation.
AB  - OBJECTIVE: To determine the natural history of fluid collections that occur
      within the osseous tunnel after autologous hamstring repair of the anterior
      cruciate ligament (ACL) and to correlate with clinical outcomes. METHODS: Twenty
      two patients were imaged within 1 year after autologous hamstring repair of the
      ACL and evaluated for the presence of fluid collections within the osseous
      tunnels. Eight patients with fluid collections were then re-evaluated with MRI
      within 6 to 9 months. RESULTS: Fourteen of 22 (64%) of the initial MRI studies
      demonstrated fluid collections within one of the osseous tunnels. Eight of these
      14 patients were available for follow-up imaging and clinical evaluation. Fluid
      collections resolved in 7 of the 8 patients, and in a single patient, the size of
      the fluid collection decreased. No patient developed ganglion formation or tunnel
      expansion, and all patients were clinically asymptomatic with no evidence of
      instability. CONCLUSION: Small fluid collections in the osseous tunnels are a
      common finding on MRI within the first year after ACL repair with an autologous
      hamstring graft. The fluid collections usually resolve over time and do not
      progress to ganglion formation or lead to tunnel expansion. They are not
      associated with clinical instability.

PMID- 12218831
TI  - Diffusion-weighted imaging of cerebral infarctions: are higher B values better?
AB  - PURPOSE: The purpose of this work is to determine whether high -value ( = 3,000
      s/mm ) diffusion-weighted (DW) imaging is superior to low -value ( = 1,000 s/mm )
      DW imaging for the detection of cerebral infarctions older than 6 h. METHOD: Echo
      planar DW imaging was performed at 1.5 T in 26 consecutive patients (mean age 66
      years) referred for clinical diagnosis of definite acute/subacute cerebral
      infarction (6 h to 14 days old). The DW imaging sequences were performed using
      matched parameters (TR = 10,000 ms, TE (eff)= 97 ms, FOV = 24 cm, 128 x 192
      matrix, slice = 5 mm, NEX = 2) with values of 1,000 and 3,000 s/mm. Areas of
      infarction were compared visually by two experienced neuroradiologists.
      Quantitative measures of MR signal and noise levels in the infarcted areas
      compared with contralateral normal brain were also obtained. RESULTS: The median
      time after infarction was 2.5 days (range 10 h to 14 days). By visual inspection,
      all infarctions were reliably identified on both the = 1,000 and the = 3,000
      images. The gross signal ratio (infarct/normal brain) was approximately 33%
      higher in the = 3,000 images, but the = 3,000 images were rated as noticeably
      "noisier" by both observers in every case. This visual observation was confirmed
      quantitatively: The signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were
      70% and 51% higher in the = 1,000 than the = 3,000 images (p < 0.0005 for both).
      CONCLUSION: For the evaluation of late acute/subacute cerebral infarctions, high 
      value ( = 3,000 s/mm(2) ) DW imaging offers no apparent diagnostic advantages
      compared with = 1,000 images and is significantly inferior in terms of SNR and
      CNR.

PMID- 12218832
TI  - Comparison of 1.5 and 8 tesla high-resolution magnetic resonance imaging of
      lacunar infarcts.
AB  - PURPOSE: We present a case report comparing 1.5 fast spin-echo (FSE) and high
      resolution 8 Tesla (T) gradient echo (GE) MRI of a patient with multiple lacunar
      infarcts. METHODS: A 51-year-old man with a history of previous lacunar
      infarctions was studied with two-dimensional Fourier transform axial 8 T GE MRI
      using the following parameters: 3 mm thick slices skip 3 mm, flip-angle
      approximately 20 degrees, TR 800 milliseconds, TE 12 milliseconds, 1024 x 1024
      matrix, field of view (FOV) 20 cm, and bandwidth 50 kHz. These images were then
      compared with routine clinical 1.5 T T2-weighted FSE images with 5 mm thick
      sections, 256 x 256, FOV 20, TR 5650, TE 102, and 16 echo train length. RESULTS:
      The majority of the infarctions were seen as areas of high signal intensity on
      both the 1.5 and 8 T images. They were seen in the corona radiata or the basal
      ganglia. More lesions were seen on the 8 T images. Low intensity signal was best
      demonstrated on the 8 T images at segments of the periphery of a few of the
      larger infarcts. There were a few small punctate low signal intensity regions
      localized at the termination of some of the microvessels on the 8 T images only.
      The foci of decreased signal intensity in regions of chronic hemorrhage appeared
      larger on the 8 T images compared with the 1.5 T images. The 8 T images
      demonstrated direct visualization of many small vessels, primarily in the deep
      white matter, which were not visible on the 1.5 T images. On the 8 T images, some
      of the infarcts appeared to be located between the medullary veins of the deep
      white matter. CONCLUSION: This case report indicates that GE 8 T images
      demonstrate more infarctions compared with the FSE 1.5 T images. It is possible
      to simultaneously identify the microvessels of the brain, small foci of
      hemorrhage, and lacunar infarctions using 8 T MRI.

PMID- 12218833
TI  - Ischemic complication of a cerebral developmental venous anomaly: case report and
      review of the literature.
AB  - We report a case of a nonhemorrhagic infarct associated with a thrombosed
      developmental venous anomaly (DVA), with secondary gliosis and Wallerian
      degeneration. The initial MRI scan showed an acute ischemic infarct in the region
      of the DVA, seen as a region of restricted diffusion on diffusion-weighted
      imaging (DWI), with later development of encephalomalacia and Wallerian
      degeneration on follow-up MRI. No blood products were seen. We believe that
      thrombosis of the collector vein of a DVA with associated infarction is a rare
      but possible complication that should be considered within the proper clinical
      setting and can be easily and confidently diagnosed by means of DWI.

PMID- 12218834
TI  - Intracranial vascular calcifications mimicking small saccular aneurysms on CT
      angiography: a technical note and case description.
AB  - The authors describe a case of intracranial vascular calcifications that mimicked
      small saccular aneurysms on CT angiography (CTA). The density of two vascular
      calcifications was visually similar to that of contrast in the parent vessel,
      making them indistinguishable from aneurysmal outpouchings. Comparison of the CTA
      with the non-contrast head CT (NCCT) was critical to distinguish low-density
      calcifications from tiny aneurysms.

PMID- 12218835
TI  - Detection of acute cytotoxic changes in progressive neuronal degeneration of
      childhood with liver disease (Alpers-Huttenlocher syndrome) using diffusion
      weighted MRI and MR spectroscopy.
AB  - Alpers-Huttenlocher syndrome (AHS) is a rare mitochondrial disorder of childhood
      onset that is characterized by progressive encephalopathy and hepatopathy. MRI
      studies are rare and have not added substantial information to the pathogenesis
      of the encephalopathy. Diffusion-weighted MRI (DWI) and MR spectroscopy (MRS)
      were used in a patient with AHS during acute clinical deterioration and after
      improvement. DWI detected signal hyperintensity in several brain areas not
      restricted to any vascular territory. MRS revealed an unequivocal lactate peak
      and a reduced N-acetyl-aspartate-creatinine (NAA/Crea) ratio. DWI signal
      hyperintensity was correlated with neurologic symptoms and decreased after
      clinical improvement. Potentially reversible neuronal cytotoxic edema resulting
      from acute impairment of mitochondrial function is strongly suggested to be an
      important pathogenetic mechanism in AHS encephalopathy.

PMID- 12218836
TI  - Chronic subdural hemorrhage into a giant arachnoidal cyst (Galassi classification
      type III).
AB  - The authors present CT and MRI of a patient with an extremely large arachnoidal
      cyst (Galassi classification type III). The cyst extended from the base of the
      skull, posterior to the brain stem, on the base of the temporal lobe over the
      complete convexity of the left hemisphere. The cyst consisted of multiple
      compartments with intracystic septa and was accompanied by a chronic subdural
      hemorrhage in the compartments. After contrast agent application, the typical
      characteristics of chronic subdural membranes were found. Besides bony
      deformities, a thinning of the inner table was found. The patient underwent
      craniotomy for evacuation of the hemorrhage and fenestration of the septa while
      he was free of symptoms. This is a remarkable case proving that chronic local
      intracranial pressure does not inevitably lead to neurologic symptoms or
      intellectual disabilities.

PMID- 12218837
TI  - Diffusion-weighted MRI of the cervical cord in acute spinal cord injury with type
      II odontoid fracture.
AB  - The authors present a case of acute spinal cord injury demonstrated by diffusion
      weighted MRI (DWI) of the cervical cord. DWI taken 2 hours after injury showed
      intramedullary hyperintensity with a decrease of the apparent diffusion
      coefficient (ADC) value at C1-C2 vertebral levels. On T -weighted images obtained
      1 month after injury, the lesion was hyperintense, indicating the existence of
      myelomalacia. DWI of the cervical cord provided satisfactory images and was a
      useful method for detecting and visualizing of the affected cord in the super
      early stage.(2)

PMID- 12218838
TI  - A functional imaging guide to the bony landmarks of the seventh nerve.
AB  - This article links the imaging anatomy of the skull base with the seventh cranial
      nerve's pathway. The specific landmarks are illustrated, and the clinical
      presentations of lesions are defined. Unifying the anatomic and clinical features
      of the seventh nerve will improve detection of small lesions, assist in
      communication between clinicians, and aid in teaching this complex subject.

PMID- 12218839
TI  - Azithromycin versus doxycycline for genital chlamydial infections: a meta
      analysis of randomized clinical trials.
AB  - BACKGROUND: Azithromycin and doxycycline are recommended for treatment of genital
      Chlamydia trachomatis infection. A systematic review comparing these antibiotics
      could affect treatment guidelines. GOAL: The goal was to perform a meta-analysis
      to evaluate the efficacy and tolerance of azithromycin versus doxycycline for
      genital chlamydial infection. STUDY DESIGN: Studies were identified by searching
      computerized English-language databases for the period 1975 to August 2001,
      supplemented by a manual bibliographic search. Criteria for inclusion were (1)
      randomized trial design; (2) regimens of oral doxycycline (100 mg twice daily for
      7 days) and oral azithromycin (1 g once); (3) males >15 years of age and
      nonpregnant females >15 years of age; (4) and evaluation of microbial cure at
      follow-up. Data were extracted on diagnostic assay, follow-up time, study design,
      sponsorship, patients' characteristics, adverse events, attrition rates, and
      outcomes. RESULTS: Twelve trials met the inclusion criteria; 1543 patients were
      evaluated for microbial cure and 2171 for adverse events. Cure rates were 97% for
      azithromycin and 98% for doxycycline. Adverse events occurred in 25% and 23% of
      patients treated with azithromycin and doxycycline, respectively. After pooling
      of the data, differences in efficacy and risk were computed. The efficacy
      difference for microbial cure (0.01; 95% CI, -0.01-0.02) and the risk difference
      for adverse events (0.01; 95% CI, -0.02-0.04) between the two drugs were not
      statistically significant. CONCLUSION: Azithromycin and doxycycline are equally
      efficacious in achieving microbial cure and have similar tolerability. Further
      head-to-head trials comparing these antibiotics are unnecessary.

PMID- 12218840
TI  - Association of adolescents' history of sexually transmitted disease (STD) and
      their current high-risk behavior and STD status: a case for intensifying clinic
      based prevention efforts.
AB  - BACKGROUND: Adolescents are at high risk of sexually transmitted disease
      (STD)/HIV infection, and one vulnerable subgroup is African American females. The
      association between adolescents' previous experience of STD and recent sexual
      risk behaviors has been ill-defined. GOAL: The goal was to examine the
      associations between adolescents' self-reported history of STD diagnosis and
      current sexual risk behaviors, prevention knowledge and attitudes, and STD
      infection status. STUDY DESIGN: This was a cross-sectional survey. Recruitment
      sites were in low-income neighborhoods of Birmingham, Alabama, characterized by
      high rates of unemployment, substance abuse, violence, and STDs. Participants
      were sexually active adolescent females (N = 522) 14 to 18 years of age.
      Information on STD history and current sexual behaviors (within the 30 days
      before assessment) was collected in face-to-face interviews. Less sensitive
      topics, such as STD prevention knowledge, attitudes about condom use, and
      perceived barriers to condom use, were addressed via self-administered survey.
      DNA amplification of vaginal swab specimens provided by the adolescents was
      performed to determine current STD status. Outcomes associated with past STD
      diagnosis were determined by means of logistic regression to calculate adjusted
      odds ratios (AORs) in the presence of observed covariates. RESULTS: Twenty-six
      percent of adolescents reported ever having an STD diagnosed. Although past STD
      diagnosis was associated with increased STD prevention knowledge, it was not
      associated with increased motivation to use condoms. Compared with adolescents
      who had never had an STD, adolescents with a history of diagnosed STD were more
      likely to report not using a condom at most recent intercourse (AOR = 2.54; 95%
      CI = 1.64-3.93; = 0.0001), recent unprotected vaginal intercourse (AOR = 1.79;
      95% CI = 1.15-2.79; = 0.010), inconsistent condom use (AOR = 2.27; 95% CI = 1.46
      3.51; < .0001), sexual intercourse while drinking alcohol (AOR = 2.09; 95% CI =
      1.33-3.28; = 0.001), and unprotected intercourse with multiple partners (AOR =
      3.29; 95% CI = 1.09-9.89; = 0.034). Past STD diagnosis was associated with
      increased risk for current biologically confirmed gonorrhea and trichomoniasis
      (AOR = 2.48; 95% CI = 1.09-5.23; = 0.030; and AOR = 2.05; 95% CI = 1.18-3.59; =
      0.011, respectively). Past STD diagnosis was not significantly associated with
      increased risk of current biologically confirmed chlamydia (AOR = 0.78; 95% CI =
      0.45-1.37; = 0.38). CONCLUSION: Among this sample of female adolescents, past STD
      diagnosis was an indicator of current high-risk sexual activity and increased
      risk for two common STDs: gonorrhea and trichomoniasis. Although adolescents may
      gain factual knowledge from the experience of having an STD diagnosed, they are
      not applying that knowledge to their current sexual behaviors. Thus, these
      adolescents remain at risk for subsequent STD infection. Therefore, the findings
      suggest that there is a need to intensify clinic-based prevention efforts
      directed toward adolescents with a history of STDs, as a strategy for reducing
      STD-associated risk behaviors and, consequently, the likelihood of new STD
      infections.

PMID- 12218841
TI  - Sexual behavior of international travelers visiting Peru.
AB  - BACKGROUND: Sexual behavior of travelers to Latin America and the sexual behavior
      of US travelers in general are poorly characterized. GOAL: The goal of the study
      was to evaluate sexual risk factors of travelers to Peru. STUDY DESIGN: Anonymous
      written questionnaires were administered to 442/507 (87%) of the individuals
      approached in the international departures area of the Lima airport. RESULTS: Of
      the 442 respondents, 54 (12.2%) had new sex partners during their stay. Sex with
      a local partner (35/52; 67.3%) was more frequent than sex with other travelers
      (18/52; 34.6%) or with sex workers (4/52; 7.7%). Risk factors for a new sex
      partner included male sex (relative risk, 1.94), single marital status (relative
      risk, 2.59), duration of stay longer than 30 days (relative risk, 5.05),
      traveling alone or with friends (relative risk, 2.88), and bisexual orientation
      (relative risk, 4.94). Frequency of sexual activity among US travelers was
      greater than that among travelers from other countries (15.2% [22/145] versus
      10.6% [30/282]; NS). Condoms were consistently used by 12/50 (24%) and sometimes
      used by 10/50 (20%), including 8/20 United States travelers and 13/29 travelers
      from other countries. CONCLUSION: Behaviors and risk factors are similar to those
      described for travelers to Africa, Asia, and Eastern Europe. Behavior of US
      travelers did not differ from that of other travelers.

PMID- 12218842
TI  - Examination of Chlamydia trachomatis infection in environments mimicking normal
      and abnormal vaginal pH.
AB  - BACKGROUND: It has long been assumed that a healthy acidic vaginal environment
      inhibits infection by Chlamydia trachomatis. The research objectives were to
      evaluate the effect of pH on C trachomatis infection by two in vitro methods, to
      assess pH effect at different serial dilutions of C trachomatis elementary bodies
      (EBs), and to examine protection by an antibiotic peptide, protegrin (PG-1), over
      a pH range. GOALS: The goals of this study were to test the hypothesis that
      acidic pH inhibits C trachomatis infection and to determine the ability of PG-1
      to provide protection at acidic and neutral pH. STUDY DESIGN: The effect of pH on
      C trachomatis was examined using two pH-adjusted preincubation shell vial assays.
      C trachomatis EBs (serovars L2, D, and E) were exposed to pH-adjusted media, with
      and without PG-1, and infection was assessed by inclusion forming unit (IFU)
      formation in McCoy cell monolayers. RESULTS: Acidic pH in preincubation media
      markedly decreased IFUs by both in vitro methods. Serial dilution experiments
      showed a 3- to 10-fold reduction in IFUs for C trachomatis (L2 and E) at pH 5.0,
      compared with those at pH 7.5. C trachomatis (D) showed a 17- to 23-fold
      reduction in IFUs (serial dilutions 1:1-1:4). PG-1 protected McCoy cell
      monolayers from infection by C trachomatis after exposure to varied pH
      environments. CONCLUSION: Acidic pH exposure significantly reduced C trachomatis
      infection in vitro. Our results support the hypothesis that a healthy acidic
      vaginal environment protects women from C trachomatis infection. In addition,
      antibiotic peptides may provide protection as topical microbicides, regardless of
      vaginal pH.

PMID- 12218843
TI  - Behaviors changed by intervention are associated with reduced STD recurrence: the
      importance of context in measurement.
AB  - BACKGROUND: Evaluations of STD/HIV interventions incorporating behavioral and
      biologic outcomes have not reported strong correspondence. GOAL: The goal of the
      study was to demonstrate that behaviors, measured comprehensively, are associated
      with infection and to delineate the behaviors responsible for reduced infection
      rates in Project SAFE (Sexual Awareness For Everyone). STUDY DESIGN: Follow-up
      data from an intervention trial were analyzed to determine: (1) study versus
      control differences in complex risk behaviors and (2) the overall relationship
      between these behaviors and infection status (chlamydia and/or gonorrhea), with
      use of multiple logistic regression. RESULTS: Lower infection rates among 249
      women who received intervention (compared with 228 controls) were explained by
      reduced-risk status in 5 modifiable behaviors. The 0 to 12-month logistic
      regression model (including sex with untreated partner [OR = 5.6], lack of mutual
      monogamy [OR = 2.4], unsafe sex [OR = 1.9], rapid partner turnover [OR = 2.7],
      and douching after sex [OR = 1.9]) correctly predicted infection status for 75.3%
      of participants (71.8% of infected, 76.2% of uninfected). Women in nonmutually
      monogamous unions who had sex with partners who were untreated or incompletely
      treated were 13 times more likely to be infected than those who were monogamous
      and avoided sex with an untreated/incompletely treated partner. CONCLUSION: This
      intervention reduced infection rates by maintaining low-risk behaviors and
      changing high-risk behaviors. We elucidated the complex relationship between
      behavior and infection by incorporating context into variable conceptualization
      and considering several behaviors simultaneously.

PMID- 12218844
TI  - A stratified approach to untangling the behavioral/biomedical outcomes conundrum.

PMID- 12218846
TI  - Factors associated with risk behaviors for sexually transmitted disease/AIDS
      among urban Brazilian women: a population-based study.
AB  - BACKGROUND: The proportion of women among persons with sexually transmitted
      disease (STD)/AIDS in Brazil is increasing rapidly, and studies are needed to
      understand risk behaviors. GOAL: The goal of this study was to identify factors
      associated with risk behaviors for acquiring STD/AIDS among women aged 15 to 49
      years in Pelotas, Brazil. STUDY DESIGN: A representative sample of women was
      surveyed by means of interviewer-administered and self-administered confidential
      questionnaires. Of the women we sought to include, 3.5% refused and 1543
      participated. RESULTS: Risk behaviors included nonuse of condoms (72%); first
      intercourse before the age of 18 years (47%); use of drugs or alcohol by the
      partner (14%) or by the woman (7%); multiple partners (7%); and anal sex (3%).
      The risk score was significantly associated with being younger than age 30 years,
      having <5 years of schooling, being divorced or separated, and being a smoker.
      CONCLUSION: Preventive strategies should prioritize efforts toward young women,
      those with little schooling, smokers, and those who are divorced or separated.

PMID- 12218845
TI  - Lymphangioma circumscriptum of the vulva following surgical and radiological
      therapy of cervical cancer.
AB  - BACKGROUND: Lymphangioma circumscriptum of the vulva rarely develops after
      postoperative pelvic irradiation. GOAL: The goal was to describe two cases of
      lymphangioma circumscriptum and their treatment and present a brief review of the
      literature. STUDY: Two female patients, aged 75 years and 46 years, presented
      with persistent edema, papules, and vesicles of the labia majora, which had
      developed 15 and 9 years after hysterectomy, lymph node dissection, and
      subsequent irradiation of cervical cancer. The external diagnosis was genital
      warts. RESULTS: In both cases histology revealed lymphangioma circumscriptum of
      the vulva. Whereas the older woman's condition responded well to laser treatment,
      keloids developed in the second patient at the site of carbon dioxide laser
      vaporization. CONCLUSION: CO2 laser treatment recently has been recommended for
      vulvar lymphangioma circumscriptum and is effective in vaporizing the
      communicating vessels to deeper cisterns. To our knowledge this is the first
      description of keloid development after laser therapy for vulvar lymphangioma
      circumscriptum, and such an effect should be considered before CO2 laser surgery
      is applied for this particular entity.

PMID- 12218847
TI  - A cost-effectiveness evaluation of testing and treatment of Chlamydia trachomatis
      infection among asymptomatic women infected with Neisseria gonorrhoeae.
AB  - BACKGROUND: Because patients infected with Neisseria gonorrhoeae are frequently
      coinfected with Chlamydia trachomatis, routine dual treatment of patients with N
      gonorrhoeae infection is frequently practiced and has long been recommended.
      GOAL: The goal of this study was to examine the cost-effectiveness of routine
      dual treatment of women with infection, with or without separate testing for C
      trachomatis, compared with an alternative of testing for both infections and
      restricting treatment for C trachomatis to women testing positive for C
      trachomatis. STUDY DESIGN: A decision analysis compared the cost-effectiveness of
      these options using cases of pelvic inflammatory disease prevented as the
      outcome. Parameter values were taken from the literature. RESULTS: Routine dual
      treatment is not an effective or cost-effective replacement for testing for C
      trachomatis, but it can increase the number of cases of C trachomatis treated
      when combined with testing. Dual treatment results in more overtreatment of
      infection C trachomatis than treatment based on test results. CONCLUSIONS:
      Testing for both infections is more cost-effective than routine presumptive
      treatment for C trachomatis. Providing both presumptive treatment and testing for
      C trachomatis can also be cost-effective in some settings.

PMID- 12218848
TI  - Condom use errors and problems among college men.
AB  - BACKGROUND: An essential yet understudied aspect of condom use is whether they
      are used correctly. GOAL: The goal of the study was to comprehensively evaluate
      condom use errors and problems reported by heterosexual college men (N = 158).
      STUDY DESIGN: A cross-sectional survey, involving a 3-month recall period, was
      conducted. RESULTS: Of the 158 participants, 60% did not discuss condom use with
      their partner before sex; 42% reported they wanted to use condoms but did not
      have any available; 43% put condoms on after starting sex; 15% removed condoms
      before ending sex; 40% did not leave space at the tip; 30% placed the condom
      upside down on the penis and had to flip it over; and 32% reported losing
      erections in association with condom use. Nearly one-third reported breakage or
      slippage during sex. Few participants reported errors related to lubrication,
      storage, and reusing condoms. Higher error scores were associated with
      breakage/slippage rather than with consistency of condom use. CONCLUSION: Condom
      use errors were common, and error scores were associated with breakage and
      slippage. Increasing the focus on correcting potential user failures may be an
      important public health strategy.

PMID- 12218850
TI  - [Kidney tumors: clinical and pathological findings and detection].
AB  - The detection and the clinical and pathological findings of kidney tumors have
      much progressed over the last 15 years. The incidence of asymptomatic renal
      masses has increased up to 30% during this time. This is mostly due to advances
      in ultrasound and computed tomography imaging. So, the therapeutic management of
      these masses has also been significantly changed. A better knowledge of their
      clinical and anatomical features allowed a more efficient mutlidisplinary
      approach and a better assessment of their prognosis.

PMID- 12218852
TI  - [Characterization of renal masses].
AB  - The characterization of renal masses relies mainly on CT which remains the gold
      standard in the diagnosis of renal tumors and cysts. Ultrasound enables to
      diagnose benign cysts which account for the majority of incidentally detected
      renal masses. MR imaging is useful in the diagnosis of renal masses that remain
      indeterminate at CT. Moreover, it is efficient as a substitute when CT is
      contraindicated. Renal masses include three categories with respect to the size
      and the gross architecture of the lesion: indeterminate very small masses (less
      than 10mm in diameter); cystic renal masses and solid renal masses that exhibit
      postcontrast tumor tissue enhancement. Characterization of cystic renal masses
      relies mainly on the Bosniak classification which consists of four categories:
      benign simple cysts (cat I); minimally complicated cysts (cat II); indeterminate
      cystic renal masses that include cystic renal tumors (multiloculated or not) and
      complex cysts; cystic renal cell carcinomas (cat IV). Solid renal masses include
      pseudotumors (normal variants, renal dysmorphisms and inflammatory renal masses)
      and renal neoplasms among which CT enable to distinct: typical large renal cell
      carcinomas, typical fat-containing angiomyolipomas and indeterminate renal
      tumors.

PMID- 12218854
TI  - [Staging and follow-up of renal cell carcinoma].
AB  - Surgery is the only curative treatment of renal cell carcinoma (RCC).
      Preoperative staging is aimed at evaluating surgical possibilities and optimal
      surgical technique. Thoracic and abdominal CT is the best way to routinely
      evaluate locoregional and metastatic extension of the tumor. However, there is no
      consensus concerning which laboratory and imaging studies should be obtained to
      assess patients after radical nephrectomy or conservative surgery. Objectives of
      this review

PMID- 12218856
TI  - [Imaging of upper urinary tract tumors].
AB  - Urothelial tumors of the upper urinary tract are mainly represented by
      transitional cell carcinomas. They are usually multifocal, synchronous or
      metachronous. Patients most often present with hematuria. Histological staging is
      according to the degree of cellular anaplasia (grade) as well as to the degree of
      wall invasion (stage). Accurate and differential diagnosis are by excretory
      urography (EU) and/or by computed tomography (CT) associated with EU. EU and
      endoscopic investigations assess tumoral extension. The most appropriate
      treatment is radical nephroureterectomy with a cuff of bladder. Early and high
      recurrence is common; therefore a regular follow-up is required and depends on
      the initial treatment and the tumoral aggressiveness. This follow-up is performed
      by imaging, endoscopic and cytologic investigations.

PMID- 12218858
TI  - [Imaging and pathology of bladder tumors].
AB  - Epithelial bladder tumors are very common. Multiple lesions are possible with
      variable degrees of malignant potential. Benign and mesenchymal tumors are much
      less frequent. The role of imaging is to first raise the possibility of such a
      tumor and then to provide pretreatment staging. Cystoscopy with tumoral resection
      and histological diagnosis remains essential for adequate treatment selection.
      Ultrafast MR imaging may be very valuable for evaluation of these tumors.
      Posttreatment follow-up is needed to detect recurrent tumors. Intravenous
      urography remains valuable for evaluation of the upper tracts.

PMID- 12218860
TI  - [Role of imaging in the diagnosis and staging of prostatic adenocarcinomas].
AB  - Early diagnosis of prostate cancer remains a subject of concern, if limitation of
      the number of unnecessary biopsies is the final goal. As long as a sufficiently
      sensitive and specific marker will not be available, high quality color-Doppler
      sonography remains a good adjunct to PSA assay to optimally select candidates to
      TRUS guided biopsies. Moreover, it greatly contributes to the local staging of
      clinically localized prostate cancer by targeting biopsies of the periprostatic
      spaces and seminal vesicles, when indicated. Endorectal MRI permits to assert for
      a given individual occult extraprostatic spread with a 95% specificity. However,
      it is only useful in patients with intermediate or high risk of pT3 stage,
      defined by the number of sextants involved on biopsy, PSA level and digital
      rectal examination findings. Indications of CT scanner and bone scan scintigraphy
      follow similar rules.

PMID- 12218862
TI  - [Imaging of testicular tumors].
AB  - Testicular cancer is the most common malignancy in young men and its incidence is
      increasing. The overall rate of cure can exceed 90% when management is optimal.
      Ultrasonography for diagnosis and thoraco-abdominal CT for staging are the
      optimal imaging modalities. In this paper we analyze technical parameters as well
      as findings and the strategy of examinations in testicular neoplasm.

PMID- 12218864
TI  - [Imaging of adrenal tumors].
AB  - Adrenal masses may be discovered incidentally by sonography. Nevertheless, CT is
      the modality of choice for the detection of adrenal mass when primary or
      secondary neoplasm is suspected. The distinction between benign and metastatic
      lesions relies mainly on the relatively high lipid content of most of the
      adenomas. CT (evaluation of non-enhanced attenuation) and MRI (chemical shift
      imaging) have comparable performances in the evaluation of lipid content. Lipid
      poor adenomas benefit from the evaluation of tumoral wash-out, and, if necessary,
      CT-guided biopsy. Primary neoplasms are uncommon, reliability of biopsy is poor
      and surgical resection is generally performed.

PMID- 12218866
TI  - [Comparison of magnetic resonance imaging with histopathological correlation in
      laryngeal carcinomas].
AB  - Apart from a clinical examination including direct laryngoscopy and biopsy,
      pretherapeutic staging for local extension of laryngeal carcinoma requires
      computed tomography. The role of magnetic resonance imaging (MRI) remains
      controversial. The aim of this study was to determine its value for detecting
      invasion of the main laryngeal structures. Histological findings were compared
      with axial MRI slices to remain in the same plane. A double-blind study of 10
      areas of the larynx was performed: vocal muscle, anterior and posterior
      paraglottic spaces, anterior and posterior laryngeal commissures, anterior and
      posterior subglottic area, arytenoid, thyroid, and cricoid cartilages. MRI
      appeared to be the method of choice to detect neoplastic cartilage, and
      subglottic and commissural invasion. MRI allows a treatment strategy adapted to
      the areas involved by the laryngeal carcinoma.

PMID- 12218867
TI  - [Surgical methods of removal of T4 nasopharyngeal malignancies. A preliminary
      report on 18 cases].
AB  - OBJECTIVES: To describe the technique and evaluate postoperative sequelae and
      results of transfacial surgical removal of T4N0 nasopharyngeal malignant
      neoplasms. MATERIAL AND METHODS: Eighteen cases of surgically-treated
      nasopharyngeal cancers, managed between january 1993 and october 2000, were
      retrospectively studied. Three patients were non-responders to neoadjuvant
      chemotherapy, 6 suffered local recurrence following standard treatment and 7 were
      operated first either because of a huge and osteolytic tumor or because of an
      uncommon histolopathology. RESULTS: Preoperative Vth nerve neuralgia (8 cases)
      was alleviated (4 cases) or cured (3 cases). At the time of diagnosis,
      ophthalmoplegia was observed in 3 cases. It disappeared postoperatively in 2
      cases and after following radiation therapy in one. Median follow-up of the
      series was of 31.8 mths. Four patients were died of disease; one of them from
      distant metastases 4 years post-surgery. One patient is alive with distant
      metastases. The 13 last (72.2%) are alive without disease with a 35.6 mths median
      follow-up (6-77 mths). DISCUSSION: This short and heterogeneous series cannot
      lead to any evidence-based conclusion. But mid-term free-of-disease survival of 4
      of the 5 patients suffering local recurrence and of patients presenting with so
      called non-radiation-sensitive tumors is to be considered. In comparison with the
      high risk of neurological sequels following reirradiation, absence of specific
      toxicity of surgery observed in this series is to be underlined. CONCLUSION: In
      selected cases surgical treatment does not demonstrate any toxicity and is able
      to offer mid-term local control of the disease. Its role is to be evaluated
      further before inclusion in the therapeutic algorithm of these very bad prognosis
      associated tumors.

PMID- 12218868
TI  - [Drainage after thyroid surgery: 264 patients].
AB  - OBJECTIVES: A prospective study was conducted in 1996-1997 in 100 patients who
      underwent thyroid surgery and who were randomly assigned to receive drainage or
      not. No statistical difference in complication rate was observed. The aim of the
      present retrospective study was to assess the consequences of this attitude in
      patients undergoing surgery since that time and to determine the number of
      postoperative complications, length of hospital stay, and type of thyroidectomy
      where cervical drains still appear to be indicated. PATIENTS AND METHODS: Total
      or partial thyroid surgery was performed in 264 patients between June 1997 and
      October 2000. Neck dissection was associated with 24 patients. RESULTS: Cervical
      drains were used in 29 patients (10.9%). Postoperative complications were
      comparable to those commonly reported. CONCLUSION: Except for neck dissection and
      mediastinal extension, thyroidectomy can be safely performed without drainage.
      This attitude reduces the overall hospital stay.

PMID- 12218869
TI  - [Binaural cochlear implantation: general concept, surgical technique and
      electrophysiology].
AB  - Cochlear implant have been proven to be safe and cost-effective in deafened
      adults. Generally, a single cochlear implants is proposed providing monaural
      audition. Some teams have published interesting results in patients wearing two
      cochlear implants. The cost of the surgical procedure is greatly increased for
      bilateral implantation. In an attempt to provide patients with binaural hearing
      and a better chance to improve their capacity for frequency discrimination
      without an excessive increase in cost, we developed an new concept and design for
      binaural cochlear implants. The aim of the present study was to establish the
      surgical technique for binaural cochlear implantation with a single internal
      receptor-stimulator. We report descriptive data on surgical procedures performed
      in two cadavers and in two deafened adults. The special implant is composed of a
      single receptor-stimulator and two electrode arrays: a short one implanted into
      the ipsilateral ear and a long one in the contralateral ear. A specially designed
      tool for endoscopic facial lifting was used to create subcutaneous tunnels from
      the ipsilateral to the contralateral ear. Insertion into cochleas was
      unremarkable. Additional time for surgery (compared with mean operative time for
      routine adult surgery in our unit), and surgical details are discussed. Binaural
      cochlear implantation is feasible, easy and not very time consuming. Studies are
      in progress to determine patient benefit. Obtaining auditory brainstem evoked
      potentials electrically in patients with binaural cochlear implants is possible
      and provides an interesting mode for in vivo analysis of the long-term effect of
      profound/total deafness on neural transmission. In our patients, results have
      demonstrated that neural response properties in auditory pathways are negatively
      related to duration of deafness.

PMID- 12218870
TI  - [Munchausen syndrome mimicking Meniere's disease].
AB  - We report the case of a female patient presenting what appeared to be Meniere's
      disease but which was found to correspond to Munchausen syndrome. Patients
      suffering from Munchausen syndrome fake their disease trying to obtain
      unnecessary treatment or surgical intervention, mimicking symptoms they learn by
      reading scientific journal or the Internet. In this patient, the diagnosis was
      made because the patient mimicked bilateral hearing loss. Specialists should be
      aware of Munchausen syndrome which can be expressed by a myriad of forms. The
      unemotional and detached way these patients describe their symptoms should alert
      the clinician to the possibility of an imaginary disease.

PMID- 12218871
TI  - [Normative data of the Biolfa(R) olfactory test].
AB  - OBJECTIVES: To evaluate the feasibility of the Biolfa(R) olfaction test and
      establish normative values. PATIENTS AND METHODS: The new Biolfa(R) olfaction
      test includes a quantitative test to measure the olfactory threshold of three
      substances in a concentration range from 1 to 9 and a semi-quantitative test to
      assess olfactory "acuteness" for eight substances. Substances used for this test
      entail non-significant trigeminal stimulation. A population of 28 women and 24
      men without olfactory dysfunction were tested. RESULTS: The olfactory threshold
      obtained with the quantitative test ranged from 5.86 to 9.54 for women, and from
      6.4 to 9.6 for men. Analysis of the thresholds identified with the semi
      quantitative test enabled establishing normative values for recognition of the
      eight substances. These values were reported on a diagram to allow partial
      translation of each subject's olfactory "acuteness". Olfactory threshold and
      smell identification ability were statistically superior for women. CONCLUSION:
      The Biolfa(R) olfaction test is the first allowing determination of both the
      olfactory threshold and quantification of smell identification ability. Normative
      values were obtained in this study to detect disease states.

PMID- 12218872
TI  - [Aspergillosis of the paranasal sinus and environmental factors].
AB  - Paranasal sinus aspergilloma is a non-invasive form of Aspergillus infection
      being encountered more often during the last decade. METHODS: A survey of
      specialists in France was carried out in 1998 to investigate the role of
      environment in the pathogenesis of the disease. RESULTS: A total of 402 patients'
      reports were reviewed, most of which involved unilaterally the maxillary sinus.
      We observed a predominance of women (sex ratio 1.9) and dental care in the past
      of 338/402 patients (84.1%). Environmental exposure that could interfere with
      aspergilloma were found in only 136 patients (33.8%) and in 21/48 (43.8%)
      patients who had had no dental care. CONCLUSION: Aspergilloma of the paranasal
      sinus has probably a multifactorial etiology, we could not point out
      environmental factors in this survey.

PMID- 12218873
TI  - [Bronchial foreign bodies in children].
AB  - BACKGROUND: Tracheobronchial aspiration of foreign bodies in children is a rare
      event that can be serious. We report a 10-year retrospective study of
      tracheobronchial foreign body aspiration in children. METHOD: This retrospective
      analysis involved 87 patients who underwent endoscopy at the ENT unit of the Caen
      University Hospital. RESULTS: Foreign bodies were found in 34 of the 87 patients.
      Average age was 3 years, with a male predominance. Peanuts were the most common
      foreign bodies observed (16/34). Most of the foreign bodies were removed via the
      right main bronchus (17/34). Clinical and radiological signs depended on delay to
      admission and were found to be normal in 15% and 37.5% of the cases respectively.
      Twenty-four children out of 34 had a positive history of foreign body inhalation.
      All foreign bodies were removed during the endoscopy procedure. CONCLUSION: This
      work underlines the much-debated function of chest x-ray, the need for a rigorous
      technically correct endoscopy procedure and the importance of close cooperation
      between the anesthesiologist and the endoscopist.

PMID- 12218874
TI  - [Hemangiopericytoma of the infratemporalis fossa: a multi-operated patient].
AB  - Hemangiopericytoma (HPC) was diagnosed in a 65-year-old man in 1991. Initially
      the tumor was located in the maxillary sinus. Resection was followed by multiple
      recurrences involving the infratemporalis fossa (ITF), the nasopharyngeal region,
      and the right tonsillar region. Over a 10-year-old period, the histology pattern
      remained unchanged. Multiple approaches, as described in the literature, were
      used for resection depending on the site of the recurrence. To data, no malignant
      structure has been identified. Pain and cranial nerve deficits (V2, V3) have been
      the main squeleae. This case points out the limitations of radical resection
      because of the difficulty of the approach to this anatomic region. CT scan must
      be performed to choose the best access route depending on the primary site of the
      tumor and its extension.

PMID- 12218875
TI  - [Tracheocele: a rare cause of pharyngeal disorders].
AB  - A 40-year-old woman with an uneventful history consulted for an episode of
      cervical swelling and pharyngeal disorders with sensation of a foreign body.
      Cervical and ENT examination was normal. The barium swallow showed a normal
      esophagus and the CT scan showed an air image in the right side of the trachea.
      The diagnosis of tracheocele was made at surgery and was confirmed by histology.
      Clinical, endoscopic, and radiologic outcome was favorable three months after
      surgical resection of the diverticulum. Tracheocele is rarely reported in the
      literature. It results from a congenital or acquired weakness of the tracheal
      wall. The right side is involved more frequently. No specific signs or symptoms
      have been identified. Diagnosis is often based on CT findings. Surgery confirms
      the diagnosis and allows resection.

PMID- 12218876
TI  - [Why do the great majority of drug users infected with the hepatitis C virus
      remain untreated?].

PMID- 12218877
TI  - [Drug users attending at hospital emergency rooms. Changes in sociodemographic
      features, health care, referral attitudes and impact of substitution therapy,
      between 1993 and 1998].
AB  - The purpose of this work was to assess changes observed between 1993 and 1998
      relative to drug users seen at hospital emergency rooms. We retrospectively
      reviewed our medical files for two periods, 1993-1995 and 1996-1998, i.e. before
      and after routine institution of substitution therapy with buprenorphine and
      methadone. A predefined grid was used to select files. All patients whose file
      indicated drug use, irrespective of the reason for consultation, were eligible
      for inclusion. Overall demographic features were: mean age 29 years, men 74%,
      known address 60%, indication of medical coverage 29%, institutional
      transportation 70%, heroine abusers 53%, injecting drug users 65%, associated
      acute alcohol intoxication 27%. There was a significant decline in the incidence
      of drug abusers during the second period (2.42% versus 3.44%) with no difference
      for age, sex, or area of residence. Documentation of medical coverage improved.
      There was no change in the hour of arrival, more than 50% arrived outside regular
      hospital hours but a higher proportion arrived during the weekend, indicating
      some access difficulty. Our results are in agreement with the OFDT data on
      product use: reduction in the use of heroine and significant increase in the use
      of cocaine, alcohol consumption remaining unchanged. Among the 63 patients seen
      during the second period, 31.7% stated they were taking substitution therapy,
      indicating this population has access to treatment. There was no statistical
      difference for diagnosis, but certain trends were observed: acute intoxication
      with loss of consciousness leading to emergency squad transfer to the emergency
      room remained the most common situation, rate of trauma was unchanged at
      approximately 10%, as was the rate of post-IV abscesses; there was a 3-fold
      reduction in request for drugs and a 2-fold rise in public intoxication. These
      data help better define management conditions for drug users attending emergency
      rooms.

PMID- 12218878
TI  - [Frequency of re-incarcerations in the same detention center: role of
      substitution therapy. A preliminary retrospective analysis].
AB  - A retrospective study was carried out using 3 606 medical files of nine detention
      centers in France, over a three-month period (May to July 1997). The files were
      analyzed to determine, age, type of addiction and subsequent type of therapy
      proposed: methadone, high-dose buprenorphine or abstinence. A comparison was then
      made to determine whether or not there exists a statistical relationship between
      the type of therapy given in prison for drug abuse and subsequent recurrent use
      during the following three and a half years, until December 2000.

PMID- 12218879
TI  - Economic and social effects of high-dose buprenorphine substitution therapy. Six
      month results.
AB  - The purpose of this study was to analyze the impact of high-dose buprenorphine
      substitution therapy in opiate-dependent patients in terms of use of psychoactive
      substances, associated risks, social integration, and the social cost generated
      by the use of these substances. This was a longitudinal quantitative survey
      carried out in 1083 patients who were evaluated at three times: at the beginning
      of substitution therapy (D0), at 6 months and then at 12 months follow up (M6,
      M12). Data were collected with an anonymous self-administered questionnaire,
      completed in the presence of an investigating physician. Results demonstrated
      that patients treated with high-dose buprenorphine for 6 months, consumed fewer
      psychoactive drugs (heroin, cocaine, benzodiazepines) and had fewer associated
      risks. Additionally, several criteria involved in social integration showed
      improvement; morbidity and mortality decreased after the first 6 months of
      substitution therapy. These improvements were followed by a reduction in the
      social cost of drug use generated by the group of patients considered. These
      initial results require confirmation in the final analysis of the study taking
      into account the 12-month follow up.

PMID- 12218880
TI  - [Acute complications in cocaine users].
AB  - Cocaine use has increased considerably during the last twenty years and several
      related complications can be identified. Clinical features of cocaine
      intoxication are variable, but predominantly involve cardiovascular events. Chest
      pain is the most main complaint; myocardial ischemia must be ruled out. Other
      cardiovascular manifestations are left ventricular dysfunction, arrhythmia,
      endocarditis and aortic dissection. Non-cardiac complications include
      neurological (seizures, stroke, cerebral hemorrhage), respiratory (asthma,
      interstitial pneumonitis, pulmonary edema), renal (acute renal failure,
      rhabdomyolysis) and obstetrical disorders. Detection of cocaine in the urine
      provides the diagnosis. Symptomatic treatment is generally given, combining
      conventional treatment of the complication and broad use of benzodiazepines.

PMID- 12218881
TI  - [Behavioral and cognitive therapy to break the smoking habit. Review of the
      literature].
AB  - Nicotine addiction is a chronic disease characterized by frequent relapse.
      Pharmacological and psychological factors are involved and must be specifically
      addressed in addicts under treatment. Physicians are familiar with
      pharmacological treatment with nicotine replacement therapy and bupropion, but
      not with psychological approaches such as behavioral and cognitive therapy.
      Various techniques have been evaluated during smoking cessation trials: aversive
      therapy, contracts, social support, stimulus control, relaxation, diet and
      nicotine fading. Such approaches have been completed with cognitive strategies
      and therapeutic programs often use motivational interviews, skills training and
      relapse prevention strategies. This article reviews these techniques and presents
      the results of a recent meta-analysis evaluating their efficacy. These results
      confirm the efficacy of behavioral and cognitive therapy in smoking cessation.

PMID- 12218882
TI  - [Is double diagnosis appropriate? A case of schizophrenia and heroine addiction].
AB  - We present a clinical case of a psychotic drug abuser. The diagnostic hypothesis
      was paranoid schizophrenia. This case clearly demonstrates the diagnostic duel
      between schizophrenia and heroine addiction. Based on this case, we hypothesize
      that use of drugs in such a patient fulfils an appeasing function rather than
      pathological burial. It would be interesting to determine the specificity of how
      this type of patient uses drugs, beyond the apparent double incidence of two
      diagnoses, in the mode of decompensation and chronic progression of the disease,
      which would be particularly useful for developing a treatment strategy.

PMID- 12218883
TI  - Cardiovascular complications of cocaine use: recent points on cocaethylene
      toxicity.

PMID- 12218884
TI  - About the article of M. Pierrot et al.: "Intoxications by hallucinogenic
      mushrooms".

PMID- 12218885
TI  - [Alexithymia and alcohol dependence].
AB  - Alexithymia is a term introduced by Sifneos in 1973 to describe, initially in
      psychosomatic patients, the inability to recognize and to express emotions. Since
      1973, alexithymia has been also described in alcohol dependence. A review of
      these studies is proposed with the results of our study from the INSERM network
      "Dependence". Prevalence of alexithymia is high in alcoholic patients, between 40
      and 60%. Some authors have found that alexithymia predicted poor outcome in these
      patients. The distinction between primary and secondary alexithymia and the
      relationships between depression and alexithymia are complex. The psychodynamic
      hypothesis that alexithymia could hold a central position secondary to early
      dysfunction in the construction of the psychic and somatic self can be put
      forward. In some circumstances, regression to this position, even after transient
      addictive filling-in, could lead to essential depression and to psychosomatic
      disease.

PMID- 12218886
TI  - [Masculine anorexia nervosa: realities and perspectives].
AB  - Since its description by Morton in 1694, masculine anorexia nervosa has been the
      subject of much debate. For many, two questions remain unanswered: does anorexia
      nervosa, as described in girls, exist in boys? - if so, is it the same disease?
      We analyzed the data in the literature which demonstrate a lower incidence than
      in the female population, although estimates are probable low due to
      underdiagnosis. The behavioral aspects suggest a similarity between masculine and
      feminine anorexia nervosa although the pure restrictive forms of anorexia are
      more rare in boys. There are however a few differences. Affected boys, according
      to Crips and Burns (1990), are heavier than girls at onset of the disorder but
      present a lower body weight during certain periods of the disease. Excessive
      physical activity is more frequent as is excessive intellectual involvement
      (Margo, 1987). The problem of amenorrhea, on/off periods, is not present in the
      male form. Testosterone and sexual function decline gradually, in parallel with
      the state of malnutrition (Anersen, 1990). The patient does not have particular
      difficulty discussing sexual relations but does exhibit a poor level of
      experience and mental representations. Contact with the opposite sex is rare and
      the fantastic life is generally very limited. The frequency of homosexual
      behavior would lie between 25% (Herzog, 1984) and 58% (Schneider and Agras,
      1987), which is higher than in the female anorexia population (Herzog, 1984).
      This observation raises the question concerning the relationship between
      masculine mental anorexia nervosa and fragile sexual identity.

PMID- 12218887
TI  - Association between first injection risk behaviors and hepatitis C seropositivity
      among injecting drug users.
AB  - HCV infection is rapidly acquired after drug addicts first inject drug
      intravenously. The risk behaviors accompanying the first intravenous substance
      injection are not well known. We used in 1997 a structured questionnaire to
      investigate the relationships between risk behaviors at the first injection and
      current reported HCV status. We interviewed 151 injecting drug users from four
      treatment centers and one prison in Paris. Risk markers for reported HCV
      seroconversion were explored by use of logistic regression models. One hundred
      and forty-three injecting drug users (95%) agreed to participate in the study. At
      the first injection, 50% shared preparation equipment; 22% borrowed and 26% lent
      injecting equipment. At the time of the study, 46% reported that they were HCV
      positive. Sharing preparation equipment (odds ratio=3.1; 95% confidence interval:
      1.2-7.8) and lending injection equipment (odds ratio=3.0; 95% confidence
      interval: 1.1-8.5) during the first injection were independently associated with
      reported HCV seropositivity. The high-risk behaviors accompanying the first
      intravenous injection of drugs justifies the implementation of specific
      prevention measures, aimed at young drug users who have not started to inject.

PMID- 12218889
TI  - [Psychiatric manifestations of systemic sclerosis].
AB  - Systemic sclerosis (SSc) is a rare conjuctive tissue disorder that is
      characterized by fibrosis of the skin and internal organs as well as vascular
      obliteration phenomenons. SSc is responsible for increased morbidity and
      mortality, and skin fibrosis may be responsible for major body changes. These
      phenomenons may contribute to the occurrence of psychological disturbances such
      as anxiety and depression, whereas the incidence of psychotic symptoms is very
      low in SSc patients. However, the prevalence of psychiatric symptoms during the
      course of SSc has not been evaluated yet with standardized evaluation scales, and
      an important breakthrough can be made in understanding the underlying mechanisms
      of psychiatric manifestations, in order to improve therapeutic management and
      quality of life.

PMID- 12218888
TI  - [Immune-based therapies and HIV infection].
AB  - The aim of immune-based therapies in HIV infection is to enhance numbers and
      function of CD4 and CD8 T lymphocytes especially specific anti-HIV cellular
      immune responses in order to allow immune control of viral replication.
      Interleukin-2 (IL-2) has been extensively studied in phase II trials.
      Intermittent administration of subcutaneous IL-2 results in substantial increases
      in CD4 cell counts in most HIV-patients. Two large-scale phase III international
      studies are addressing the key remaining question of the clinical benefit
      associated with CD4 cell expansions in HIV-infected patients receiving IL-2.
      Other cytokines including interferon-alpha are currently under investigation in
      phase II trials. The goal of therapeutic immunizations is to enhance and broaden
      the immune system's ability to recognize HIV. Several vaccine candidates, also
      tested as immunogens for preventive vaccines, are currently studied in phase II
      trials in patients exhibiting viral suppression under highly active
      antiretroviral therapy. It has been demonstrated in rhesus monkeys'models that
      therapeutic immunizations can result in the induction of strong CD4 and CD8
      responses associated with viral control and prevention of clinical AIDS,
      following challenge with a highly pathogenic strain of chimeric SIV-HIV. The
      clinical efficacy of immune-based strategies remains to be demonstrated in
      randomized controlled clinical trials. Participation of immune system to control
      of viral replication may allow simplification of antiretroviral treatment which
      results in long-term adverse effects having impact in life quality of persons
      living with HIV.

PMID- 12218890
TI  - [Cardiovascular involvement in systemic sclerosis].
AB  - Heart involvement is frequent in systemic sclerosis. Cardiomyopathy is the main
      localization but its diagnosis is often late. Cardiac echography or radionuclide
      imaging show early involvement of the myocardium while showing alterations of
      diastolic function of the left ventricle or perfusion defects. The pathogenesis
      of this cardiomyopathy is supposed to be related to myocardial ischemia in
      relation with vasospasm, or with organic lesions of small arteries or coronary
      microcirculation. Pericarditis rarely is of clinical significance. Pulmonary
      hypertension concerns patients with proximal and advanced systemic sclerosis or
      limited forms such as CREST. It can be efficiently diagnosed by doppler
      echography but its therapy is difficult and its prognosis is poor. Epoprostenol
      in continuous venous infusion seems to be efficient but the accessibility to this
      therapy is difficult. While the involvement of middle-sized arteries of the hands
      is common, systemic sclerosis seems to be associated to an increased frequency of
      large-sized arteries disease.

PMID- 12218891
TI  - [Pulmonary hypertension associated with systemic sclerosis].
AB  - Pulmonary hypertension is a rare but well known life-threatening complication of
      scleroderma and particularly in its limited variant, the CREST syndrome
      (Calcification, Raynaud phenomenon, Esophageal dysmotility, Sclerodactily,
      Telangiectasia). The aim of this article is to analyze the available literature
      and to report the experience of a center for pulmonary vascular diseases. Dyspnea
      is the main symptom and is frequently severe. Echocardiography is an excellent
      tool to detect pulmonary hypertension. However, right-heart catheterization is
      necessary to confirm the diagnosis of pulmonary hypertension and to test
      vasoreactivity with a potent vasodilator such as nitric oxide. Hemodynamic
      parameters are less severe in patients with connective tissue diseases perhaps
      because of an earlier diagnosis. A significant lower proportion of patients
      presents an acute vasodilator response suggesting an early constitution of
      irreversible pulmonary vascular lesions. Continuous intravenous epoprostenol
      therapy seems to be less effective as compared with patients with primitive
      pulmonary hypertension and does not improve survival. In our experience,
      immunosuppressive therapy does not improve hemodynamic or clinical data. Novel
      therapies including oral, sub-cutaneous or inhaled stable prostacyclin analogues
      and endothelin receptor antagonists are currently evaluated in large placebo
      controlled trials.

PMID- 12218892
TI  - [Digestive manifestations in systemic sclerosis].
AB  - Gastrointestinal involvement occurs in most patients with systemic sclerosis.
      Pathology is characterized by vasculopathy, resulting in tissue ischemia,
      progressive dysfunction and fibrosis. In its diffuse and visceral pattern,
      digestive manifestations may involve most of the intestinal tract and are the
      most frequent before renal, cardiac and pulmonary involvement. Whatever the
      visceral extension, about 80% of patients have digestive manifestations including
      gastroesophageal reflux, abnormalities of intestinal motility leading to chronic
      intestinal pseudo-obstruction and small bowel bacterial overgrowth and
      malnutrition. Long-term treatment of reflux with high-dose proton pump inhibitors
      appears safe and effective for symptom relief and may prevent recurrence of
      esophagitis and stricture. Prokinetic agents effective in pseudoobstruction
      include metoclopramide, domperidone, octreotide, and erythromycin.

PMID- 12218893
TI  - [Long-term treatments for systemic sclerosis: what are the perspectives?].
AB  - Systemic sclerosis (SSc) is responsible for fibrosis of the dermis and other
      organs as well as vascular abnormalities. While the pathogenesis of SSc is
      continually being better understood, there is still no single therapeutic agent
      that has been shown to increase survival in a prospective randomized trial.
      Traditional medications such as colchicine and D-penicillamine are disappointing
      in clinical practice, and the latter one failed to clearly show benefit when
      tested in a prospective placebo controlled trial comparing conventional high dose
      versus low dose. Conversely, new disease modifying agents are emerging such as
      cyclophosphamide (CYC) in interstitial pulmonary disease and stem cell autograft
      after high dose CYC therapy in patients who develop visceral involvement in the
      three first years of evolution of the disease. Organ specific therapy may show
      dramatic benefit, such as angiotensin converting enzyme inhibitors in renal
      crisis and epoprostenol in primary pulmonary hypertension. We will try to review
      disease modifying agents available in SSc and emphasize new therapeutic agents
      that are currently being evaluated, including vasodilators, anti-inflammatory,
      anti-fibrosing agents and immunosuppressive molecules.

PMID- 12218894
TI  - [Rectal endocrine intermediate-cell carcinoma].
AB  - An 82-year-old patient complained of diarrhea due to a rectal endocrine
      intermediate-cell carcinoma. Histology displayed a neuron-specific enolase and
      CD56 immunoreactive tumor. Hepatic metastases developed rapidly and the tumor was
      briefly reactive to radiotherapy and chemotherapy. These tumors are rare and have
      a poor prognosis. We focus on the recent classification of gastrointestinal
      endocrine tumors.

PMID- 12218895
TI  - [Sjogren-Larsson syndrome: two cases with delayed diagnosis].
AB  - INTRODUCTION: Sjogren-Larsson syndrome (SJS) is an autosomal-recessive disorder.
      Patients suffer from congenital ichtyosis, mental retardation and symmetric
      spastic paralysis. Ichtyosis is usually pronounced and associated with
      erythroderma. Neurological manifestations occur usually between 4 and 13 months
      of age. This genetic disease is due to fatty acid aldehyde dehydrogenase (FALDH)
      deficiency, leading to an accumulation of long-chain alcohols. The gene has been
      mapped to chromosome 17. CASE REPORTS: A 52-year-old woman was hospitalized
      because of a severe erythroderma with ichtyosis. She suffered from epilepsy,
      spastic diplegia and mental retardation (Little disease has been diagnosed). The
      association of spastic paraparesia and ichtyosiform erythroderma suggested the
      diagnosis of SJS. This was confirmed by the very low level of FALDH activity. A
      27-year-old patient was hospitalized for the recent onset paraparesia.
      Erythematous patches were observed on arm pits and buttocks. The diagnosis of SJS
      was not confirmed by FALDH assay. DISCUSSION: Diagnosis of Sjogren-Larsson
      syndrome is a very rare disease in France. It is useful to evoke the diagnosis
      when spastic paraparesia is associated with these unusual cutaneous signs.

PMID- 12218896
TI  - [Fabry's disease and hypoparathyroidism].
AB  - INTRODUCTION: Fabry's disease is due to alpha-galactosidase deficiency. This rare
      lysosomal storage disease is transmitted by recessive X-linked heredity.
      Sphingolipids (galactosyl-glucosyl-ceramide) accumulate in many organs. CASE
      REPORT: A 19-year-old man with known hypoparathyroidism presented with
      telangiectasia and angiokeratomas on the buttocks, the hips, the hands and around
      the navel. For many years, he suffered from paroxysmal pain in the hands and
      feet. From childhood, he had complained of diffuse abdominal pain, associated
      with diarrhea. Ophthalmological slit lamp fundus examination showed corneal
      telangiectasia and cornea verticella. There was no kidney or heart involvement.
      The diagnosis of Fabry's disease was confirmed by very low levels of alpha
      galactosidase. DISCUSSION: We did not find any other association of
      hypoparathyroidism and Fabry's disease in the literature. Hypoparathyroidism is
      not a manifestation of Fabry's disease. Idiopathic hypoparathyroidism is very
      rare and a genetic origin is known. This disease can be recessive X-linked. A co
      transmission of idiopathic hypoparathyroidism and Fabry's disease is probable in
      our patient.

PMID- 12218897
TI  - [Pulmonary artery aneurysms in Behcet's disease: contribution of imaging in 5
      cases].
AB  - Pulmonary involvement in Behcet's disease is an uncommon condition (12%).
      Thromboembolism of the superior vena cava and/or other mediastinal veins,
      aneurysms of the aorta and pulmonary arteries are the main vascular
      manifestations in addition to pulmonary infarct and intrathoracic hemorrhage.
      Despite their scarcity, respiratory symptoms may be life-threatening. The aim of
      this study was to assess the contribution of thoracic imaging for one of the most
      serious aspects of the disease: pulmonary artery aneurysm. We report five
      patients with pulmonary artery aneurysms (mean age: 39.5 years). Hemoptysia
      revealed Behcet's disease in three. Initially explored by conventional
      radiography, computed tomography and angiography, pulmonary artery aneurysms are
      currently investigated well with helicoidal computed tomography, digital
      angiography, magnetic resonance imaging (MRI) and angio-MRI. These imaging
      techniques provide helpful information for the diagnosis of Behcet's disease.

PMID- 12218898
TI  - [Pathophysiology of thrombotic microangiopathies: current understanding].
AB  - Thrombotic microangiopathies (TMA) encompass various severe diseases
      characterized by microangiopathic hemolytic anemia and peripheral
      thrombocytopenia, associated with fever, neurological signs and renal
      involvement. Microvascular thrombosis is the typical lesion, and results in
      tissue ischemia. Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic
      syndrome (HUS) are the two most classical forms. These two entities are
      clinically and histopathologically closely related. There is a body of evidence
      suggesting that endothelial cell injury is the initial event in TTP and HUS, and
      that it may be related to a large number of triggering factors, such as
      infection, connective tissue disease, drugs, cancer and chemotherapy,
      transplantation, and pregnancy. Endothelial cell injury enhances the release of
      ultra large forms of von Willebrand factor (ULvWF) multimers and other
      prothrombotic agents, such as plasminogen activator inhibitor and platelet
      activating factor, whereas it decreases the release of prostaglandin-I2, a strong
      inhibitor of platelet aggregation. Recently however, it has been shown that TTP
      and HUS were pathophysiologically distinct. Actually, TTP is associated with a
      deficiency in von Willebrand factor-cleaving protease, an enzyme involved in
      cleavage of ULvWF into circulating 200 kDa and 350 kDa fragments. This deficiency
      may be either congenital or acquired, and then related to an IgG inhibitory
      autoantibody. This protease deficiency may account for the high amounts of
      plasmatic ULvWF in TTP patients. In HUS, vWF-cleaving protease activity is found
      normal. HUS encompasses two distinct entities. Epidemic, or diarrhea-associated
      HUS, is associated with verotoxin or Shiga toxin-associated enterobacteriaceae.
      These toxins are directly responsible for endothelial cell injury. Sporadic HUS
      (also termed atypical HUS in children) is closely related to TTP, and shares the
      same triggering factors. Familial HUS has been associated in some cases with
      hypocomplementemia and factor H dysfunction, the pathophysiological role of which
      remains unclear. The study of the different triggering factors and predisposing
      factors may be useful to define different subsets of TMA, that may be
      characterized by their course and prognosis.

PMID- 12218899
TI  - [Pathogenesis of systemic scleroderma: immunological aspects].
AB  - Systemic sclerosis (SSc) is a connective tissue disorder that is characterized by
      excessive collagen synthesis by fibroblasts and by vascular hyperreactivity and
      obliteration phenomena. Excessive collagen production is the consequence of
      abnormal interactions between endothelial cells, fibroblasts and mononuclear
      cells. Immunological abnormalities are present very early in the development of
      SSc. Mononuclear cells, particularily macrophages and T lymphocytes play a
      prominent role in fibroblast activation and collagen synthesis through the
      cytokines they produce. Thus, lymphocytic infiltrates in the skin and in the lung
      are preferentially composed of CD8+ T lymphocytes, that produce important amounts
      of interleukin 4 (IL-4). The effects of IL-4 are added to these of transforming
      growth factor B (TGF-B) and connective tissue growth factor (CTGF) that stimulate
      collagen synthesis by fibroblasts. T lymphocytes produce important amounts of
      gamma interferon (INF-gamma) that is the best inhibitor of collagen synthesis by
      fibroblasts. However, the inhibitory effect of INF-gamma on collagen synthesis is
      diminished in SSc patients. Numerous autoantibodies can be evidenced in the serum
      of SSc patients. Three of them are specific for SSc and mutually exclusive: anti
      centromere antibodies (Ab) in limited SSc, anti-Scl70 Ab in diffuse SSc and anti
      RNA polymerase III Ab in diffuse SSc with renal involvement. These autoantibodies
      are good prognosis markers but their pathogenic role remains uncertain.

PMID- 12218900
TI  - [Central nervous system involvement in scleroderma].

PMID- 12218901
TI  - [CREST syndrome].
AB  - CREST syndrome has been described as a form of progressive systemic sclerosis in
      which there is relatively limited involvement of the skin, prominence of
      calcinosis, Raynaud's phenomenon, esophageal dysfunction and telangiectasia. The
      acronym CREST was coined in 1964 by Winterbauer in the USA but the very first
      case report was by French physicians Thibierge and Weissenbach in 1910.
      Antinuclear antibodies recognizing chromosomal centromere proteins are
      characteristic of CREST syndrome and are present in more than 50% of the cases.
      The prognosis of CREST syndrome is relatively good with a long lasting disease
      duration (>10 years). Two complications are seldom associated with CREST
      syndrome: digital gangrene with finger losses and pulmonary hypertension (3 to
      14% of CREST syndrome). Pulmonary hypertension is a very late event and the
      prognosis is very severe (mortality rate of 50% after 2 years).

PMID- 12218902
TI  - [Microchimerisme in systemic sclerosis].
AB  - Several studies have shown an association between the presence of systemic
      sclerosis in females and the presence of fetal cells in peripheral blood. These
      results have led to the hypothesis that systemic sclerosis (SSc) may indeed be
      the consequence of an allogeneic fetomaternal reaction. However, certain normal
      female controls also exhibit microchimerism. In addition, there are several
      clinical and histological differences between SSc and sclerodermoid graft versus
      host reaction. If microchimerism plays a role in SSc, it would therefore comprise
      one step in a multistep process. This review focuses on recent papers targeting
      microchimerism and its evaluation in SSc.

PMID- 12218903
TI  - [Scleroderma and pregnancy].
AB  - PURPOSE: - The frequency of concurrent scleroderma and pregnancy is low because
      scleroderma is a rare connective-tissue disease and the mean age of symptom onset
      is in the early 40s. The reciprocal influence of pregnancy and scleroderma and
      management of pregnancy are the purpose of this review. Current knowledge and key
      points. - There is no increase in infertility in women with scleroderma. The
      effect of pregnancy on scleroderma is a greater risk of renal crisis, especially
      when scleroderma is evolutive, diffuse and recent. Conversely, pregnancy is
      characterized by prematurity and small full-term infants because scleroderma
      induce placentar vascular abnormalities. There is no increase in miscarriages and
      spontaneous abortions. The pregnant scleroderma patient is a potential
      anaesthetic challenge because of physical difficulties and visceral involvement.
      Future and projects. - Planning of pregnancy and follow-up by a multidisciplinary
      experienced team in high risk pregnancies are guarantees for successful
      pregnancies. Future research will try to determine the role of microchimerism in
      scleroderma physiopathology and specify placental findings in order to ameliorate
      the obstetrical prognosis.

PMID- 12218904
TI  - [A rare cause of constipation: neurinoma of the fourth lumbar nerve. Case report
      and review of the literature ].
AB  - Constipation is a symptom not to be neglected, especially if the complaint is
      recent. We report a case where this symptom was the only clinical manifestation
      of a voluminous retroperitoneal tumor. The tumor was found to be a neurilemmoma
      of the fourth right lumbar roots, confirmed at pathological examination.
      Manifestations of extradural neurinomas generally result from compression of
      neighboring structures. The best preoperative diagnosis approach is magnetic
      resonance imaging but histology is required for confirmation. The close relations
      the tumor mass maintains with the unaffected nerve fibers makes resection
      difficult without postoperative functional consequences. Surgeons discuss the
      relevance of partial excision in order to preserve the nerve root in case of a
      benign slow-growing tumor. There does however appear to be a significant recovery
      of muscle strength even in case of total resection.

PMID- 12218905
TI  - [Acute deafness after carbon monoxide poisoning. Case report and review of the
      literature].
AB  - A 61-year-old man developed an extrapyramidal syndrome 15 days after an episode
      of carbon monoxide poisoning. Two months later he developed severe deafness.
      Brain imaging revealed ischemic lesions in the region of the basal ganglia.
      Audiometric studies disclosed neurosensorial deafness. The patient died nine
      months later due to respiratory complications.

PMID- 12218906
TI  - [Anti-Jo1 antibodies syndrome in an HIV-infected patient].
AB  - An HIV-infected man developed primary polymyositis (fever, myalgia, elevated
      serum muscle enzymes, and signs of inflammation) associated with serum anti-Jo1
      antibodies and pulmonary fibrosis. Anti-Jo1 antibodies are exceptional in HIV
      infected patients. We discuss the role of infection in polymyositis. HAART and
      corticosteroids led to rapid clinical and radiological improvement.

PMID- 12218907
TI  - [Candida albicans prosthetic valve endocarditis. Two cases].
AB  - TWO CASES: Candida albicans prosthetic valve endocarditis (PVE) is a rare entity
      with serious complications. We report two cases of Candida albicans PVE,
      confirmed by culture of the prosthetic valve. The first patient died twenty days
      after surgery with cerebral bleeding secondary to multiple mycotic aneurysms, the
      second patient was still alive eight months following a Saint-Jude aortic valve
      replacement and prolonged antifungal therapy. The difficulty of diagnosis and
      management are discussed.

PMID- 12218909
TI  - [The return of syphilis].

PMID- 12218908
TI  - [IgG-secreting lymphoplasmocytoid leukemia revealed by ophthalmologic
      hyperviscosity symptoms].
AB  - IgG-secreting lymphoplasmocytoid leukemia is a rare disease associating
      splenomegaly and B cell proliferation. Lymphoid phenotype is usually different
      from chronic lymphocytic leukemia. We report a case disclosed by hyperviscosity
      syndrome. Diagnosis was confirmed at routine ophthalmologic study.

PMID- 12218910
TI  - [Eosinophilic ulcer of the oral mucosa].

PMID- 12218911
TI  - [Does benign summer light eruption exist?].
AB  - BACKGROUND: Contrary to other countries, in which a unique entity is recognized,
      two sub-groups of light eruption, benign summer light eruption and polymorphous
      light eruption, are identified in France. Benign summer light eruption was
      individualized with a few criteria: age at onset between 25-35 years old, female
      predominance, onset within 12 hours after an intensive exposure to sun, presence
      of lesions on areas which have not been regularly exposed to sunlight such as the
      upper chest, absence of lesions on the face, improvement during the summer period
      and negativity of the polychromatic phototest. In fact patients usually
      presenting with benign summer light eruption do not have all the criteria and
      they gradually develop a polymorphous light eruption. The aim of this study was
      to quantify, among the patients presenting with a light eruption, the population
      with three main criteria of benign summer light eruption. PATIENTS AND METHOD:
      Eighty-seven patients presenting with a light eruption, a polymorphous light
      eruption or a benign summer light eruption, were selected by a dermatologist. For
      each patient the presence or absence of the 3 main criteria were noted: a) no
      lesion of the face, b) improvement of the eruption during the summer period, c)
      negative polychromatic phototest. RESULTS: Among the 87 patients, 9 of them (10
      p. 100) had the three main criteria of benign summer light eruption. DISCUSSION:
      Benign summer light eruption is either rare or defined with wrong criteria. The
      polychromatic phototest was gradually replaced by the UVA phototest. In fact,
      provocation UVA phototests do not individualize benign summer light eruption from
      polymorphous light eruption. Individualization of the benign summer light
      eruption is not justified because there is a continuous spectrum of light
      eruptions, ranging from the benign eruption which improves during the summer
      period and the chronic eruption with a high photosensitivy and lesions of the
      face.

PMID- 12218912
TI  - [Polychromatic phototest sensibility is superior to UVA phototest in polymorphic
      light eruptions].
AB  - BACKGROUND: The phototest is used to confirm the diagnosis of polymorphous light
      eruption and to evaluate the different treatments. The different light sources in
      the different countries explains the lack of standardization. In France, we use a
      polychromatic source emitting a radiation close to the solar spectrum. The study
      compared the efficacy of a polychromatic source with a UVA source in the photo
      induction of lesions. PATIENTS AND METHOD: Sixty-four patients presenting with a
      polymorphous light eruption were selected by a dermatologist. Polychromatic and
      UVA phototests were performed on each patient. At day 8, the phototest was
      considered positive if there were papules. RESULTS: Polychromatic and UVA
      phototests were positive in respectively 56 p. 100 and 23 p. 100 of the patients.
      Forty-one per cent of the patients had both polychromatic and UVA negative
      phototests. DISCUSSION: Polychromatic phototest seems to be more sensitive than
      UVA phototest. Induction of the lesions with a polychromatic source is so easy
      that it proves the significant role for UVB in the genesis of polymorphous light
      eruption. The percentage of negative phototests is identical to those published
      in the literature. Negative phototests are not necessarily secondary a bad
      methodology, they can individualize patients with those lower photosensitivity
      who present with a polymorphous light eruption that may resolve spontaneously.

PMID- 12218913
TI  - [Prophylactic antiretroviral therapy after sexual exposure to HIV: 93 cases].
AB  - PATIENTS AND METHODS: We studied prospectively the feasibility of post exposure
      prophylaxis against HIV in 93 subjects consulting after sexual exposure at STD
      Center of Hopital Saint-Louis. Among the 93 subjects, 76 were men (45 homosexual)
      and 17 women. RESULTS: Delay to consultation was 38 h. Among sexual exposure 90
      p. 100 were anal or vaginal intercourse and 10 p. 100 oral intercourse. Fifty
      percent were unprotected. Seventy-five percent of source subject HIV status was
      unknown, but controlled negative in 14 p. 100 of cases. Three subjects were
      infected initially. Seventy-two subjects were treated, with triple regimen, for
      30 days without severe adverse event. Twenty-five percent were lost to follow up
      before the end of treatment, only 54 controlled their serology after the end of
      treatment (after 1 month: 70 p. 100, after 2 months: 51 p. 100 and after 4-6
      months: 13 p. 100). DISCUSSION: This study underlines the difficulty in obtaining
      clinical and serological control after post exposure prophylaxis, even in a STD
      Department involved in prevention and counseling.

PMID- 12218914
TI  - [Eosinophilic ulcer of the oral mucosa: 11 cases].
AB  - BACKGROUND: The eosinophilic ulcer is a lesion of the oral mucosa, that has been
      infrequently described in the literature. This is a benign and self-limiting
      lesion of unknown origin. CASE REPORTS: In this article, eleven new cases of
      eosinophilic ulcer of the oral mucosa are presented. The clinical, histologic and
      evolutive features are reviewed. DISCUSSION: Recurrent trauma is clearly involved
      in the pathogenesis of this entity.

PMID- 12218915
TI  - [Doxycycline].
AB  - Doxycyclin is a semi-synthetic structural isomer of the tetracycline family. It
      exhibits good intra-cellular penetration, with bacteriostatic activity on many
      bacteria. Different types or bacterial resistance are known. Acquired resistance
      has a ribosomal or a plasmidic mechanism. Resistance of Propionibacterium acnes
      is secondary to a mutation of ARNr. Doxycyclin also has an anti-inflammatory
      activity, via numerous pathways. Doxycyclin is rapidly and almost completely
      absorbed by the digestive tract. Food has no incidence on the absorption. It has
      a high but labile affinity for proteins with 90 p. 100 of the molecule linked. It
      rapidly diffuses in the extravascular compartment and in most of the tissues.
      Bile excretion is the main excretion route. It occurs more slowly by the kidney
      with tubular reabsorption. The main dermatological indication is acne with daily
      dose varing between 50 mg and 100 mg. Although good assays are lacking, a large
      professional consensus has validated its use. It is also active at the same
      dosage in rosacea. Chlamydial and mycoplasma urethritis may be treated by
      doxycyclin, and this antibiotic is presently used as second choice. Many other
      diseases may be treated as a primary or secondary choice, such as treponematoses,
      brucellosis, pasteurellosis, borreliosis, rickettsioses and cholera. Some non
      infectious diseases have been occasionally treated by doxycycline. Digestive side
      effects are the more frequent. Esophageal toxicity has been reduced with tablets
      and sufficient concomitant water ingestion. Phototoxicity is dose-dependent.
      Various cutaneous side effects have been described, some of them severe. Systemic
      toxicity is rare. Pregnancy is a contra-indication, and as other tetracyclines,
      it should not be given to children and during lactation. Doxycycline is
      commercialized as tablets. No reduction of the dose is necessary in renal
      failure. Association with retinoids is not recommended. Anticoagulants are
      potentialized. Didanosin, iron, and mineral salts lower its activity.

PMID- 12218916
TI  - [Chronic lupus erythematosus presenting as acneiform lesions].
AB  - BACKGROUND: Cutaneous manifestations of lupus erythematosus are numerous but
      usually permit easy diagnosis. However, there are atypical lesions that can mimic
      benign dermatologic disorders. We report on a patient with lesions of acne
      leading to the diagnosis of chronic lupus erythematosus, and who subsequently
      developed systemic lupus erythematosus. CASE REPORT: A 30-year-old woman
      presented with inflammatory lesions and comedos on the face. The eruption started
      after her last pregnancy and was refractory to local and general treatment. She
      also complained of arthralgia, Raynaud's phenomenon and diffuse alopecia.
      Cutaneous biopsy was characteristic of chronic lupus erythematosus.
      Immunofluorescence microscopy of lesional skin showed a lupus band deposit.
      Antinuclear antibodies were highly positive. The patient was successfully treated
      with chloroquine. Three years later, the patient presented with photodistributed
      eruption. Antinuclear antibodies were still positive and in addition
      anticardiolipin antibodies were found. Final diagnosis was systemic lupus
      erythematosus. DISCUSSION: Acneiform lesions are rarely reported in lupus
      erythematosus. Only three similar cases were reported in literature. Atypical and
      treatment-resistant eruptions should attract attention. Furthermore, the
      occurrence of systemic lupus in chronic lupus erythematosus is not an unfrequent
      phenomenon and the oestrogen-dependance of chronic lupus lesions may predict this
      association.

PMID- 12218917
TI  - [Plantar pyoderma due to Stenotrophomonas maltophilia].
AB  - INTRODUCTION: Stenotrophomonas maltophilia is a Gram negative, opportunistic
      bacteria. We describe a case of community-acquired superficial pyoderma due to
      this bacteria in a immunocompetent host. CASE-REPORT: A 59-year-old man presented
      with an ulceration of the sole for two months. Several topical and systemic
      treatments had failed to cure the lesion, including oral ofloxacin for ten days.
      Microbiological study of the lesion showed numerous Gram negative bacilli with
      growth of S. maltophilia. This bacterium initially responded to ofloxacin, but
      became resistant after the oral use of this antibiotic. Finally, a topical
      treatment with polymyxin/tetracycline ointment resulted in complete healing
      within two weeks. DISCUSSION: S. maltophilia may be responsible for superficial
      pyoderma and serious opportunistic infections in immunocompetent persons. Topical
      antimicrobial therapy is efficient when oral quinolone therapy has failed to cure
      the lesion.

PMID- 12218918
TI  - [Painful edema of the feet revealing ankylosing spondylitis].
AB  - INTRODUCTION: Painful peripheral oligoarthritis can reveal ankylosing
      spondylitis. In some instances, an acral pitting edema can be the sign of this
      affection. CASE REPORT: A 39-year-old man, with no significant previous medical
      history, consulted in a dermatology department for acral pain and edema of both
      feet, which were exacerbated during the second part of the night. On examination,
      he had a pitting edema and a livedo of the distal part of the feet. Biological
      investigations revealed an inflammatory syndrome and the presence of the
      histocompatibility HLA-B27 antigen. Bone scintigraphy revealed distal
      hyperfixation on both feet. Diagnosis of ankylosing spondylitis was established.
      DISCUSSION: Late-onset ankylosing spondylitis, which appears in subjects older
      than 35 years, can manifest as peripheral arthritis with systemic signs, often in
      the absence of involvement of the axial skeleton. Peripheral pitting edema of
      lower limbs can be the presenting sign. Since cutaneous involvement can be the
      presenting sign, dermatologists should be aware of this entity.

PMID- 12218919
TI  - [Rothmund-Thomson syndrome, trisomy 8 mosaicism and RECQ4 gene mutation].
AB  - BACKGROUND: We report a case of Rothmund-Thomson syndrome associated with a
      trisomy 8 mosaicism, and RECQ4 gene mutation. OBSERVATION: An 18-year-old man
      presented with a poikiloderma affecting photoexposed areas and the buttocks. This
      lesions appeared during the first year of life and was secondly associated with
      alopecia, sparse body hair, keratosis, and warts. He also had proportional short
      stature, thumb and patella aplasia, particular facies, and plantar malformations.
      Cytogenetic studies evidenced chromosomal instability and trisomy 8 mosaicism.
      The DNA repair capacity was normal. A mutation in RECQ4 helicase gene was found.
      DISCUSSION: Rothmund-Thomson syndrome is a rare hereditary syndrome characterized
      by early onset of poikiloderma. Patients exhibit variable features including
      skeletal abnormalities, juvenile cataracts, photosensitivity, and a higher than
      expected incidence of cutaneous or extracutaneous malignancies. Genetic patterns
      found in Rothmund-Thomson syndrome are heterogeneous. Normal karyotypes have been
      demonstrated in many patients. Various karyotypic abnormalities or reduced DNA
      repair was seen in others. Recently, five patients with Rothmund-Thomson syndrome
      were shown to segregate for mutations in RECQ4 helicase gene. Thus, clinical and
      genetic features in Rothmund-Thomson syndrome are polymorphous. Therefore, it
      could be interesting to correlate genotype and phenotype.

PMID- 12218920
TI  - [Cutaneous T-cell lymphoma, cutaneous hyperpigmentation and paraneoplastic
      pemphigus].
AB  - BACKGROUND: Paraneoplastic pemphigus is an autoimmune mucocutaneous disease
      usually associated with neoplasia as lymphoid proliferations. We report the
      original case of a patient who had developed a mycosis fongoide preceded by a
      paraneoplastic pemphigus. To our knowledge, this association has never been
      reported before. Cutaneous manifestations of mycosis fongoide as pigmentary
      change are known. This mycosis fongoide was particular in its progressive
      cutaneous hyperpigmentation. CASE REPORT: A 70-year-old male patient developed a
      mycosis fongoide with CD30 positive cells in the dermis several months after the
      diagnosis of a paraneoplastic pemphigus. Simultaneously, a cutaneous
      hyperpigmentation was predominantly noticed on photo-exposed areas, which
      improved after chemotherapy. DISCUSSION: Paraneoplastic pemphigus may precede the
      cancer, as is shown by our present case. This paraneoplastic pemphigus is
      singular because of the lack of oral erosions, patient's prolonged survival and
      its association with a mycosis fongoide. The diagnosis of mycosis fongoide with
      CD30 + cells was finally established together with its relationship to the
      cutaneous hyperpigmentation. Indeed, a few cases of pigmentary changes in mycosis
      fongoide have already been reported. The pathogenesis is still unknown, but the
      role of mast cell and stem cell factor in hyperpigmented mycosis fongoide has
      been proposed.

PMID- 12218921
TI  - [Post-radiotherapy eruption in a patient treated with valproic acid. Rowell's
      syndrome?].

PMID- 12218922
TI  - [Adult tinea versicolor: a particular localization].

PMID- 12218923
TI  - [Lipschutz's genital ulceration during an Epstein-Barr virus primary infection].

PMID- 12218924
TI  - [A reddened eye].

PMID- 12218925
TI  - [A temporal pulsatile nodule].

PMID- 12218926
TI  - [A scrotal tumor].

PMID- 12218927
TI  - [Urticarial vasculitis].

PMID- 12218928
TI  - [Ocular allergies for the dermatologist: conjunctivitis].

PMID- 12218929
TI  - [Eyelid contact dermatitis].

PMID- 12218930
TI  - [Hypersensitivity to hydrocortisone 17-butyrate].

PMID- 12218931
TI  - [Hypersensitivity to group C corticosteroids].

PMID- 12218932
TI  - [Salicylic acid as a keratolytic agent].

PMID- 12218933
TI  - [Arrows and variola scars].

PMID- 12218934
TI  - [Marie Nicolas Devergie, the elder: a forgotten person].

PMID- 12218935
TI  - Repeated intravenous doses of all-trans-retinoyl beta-D-glucuronide is not
      effective in the treatment of bacterial bronchopneumonia in lambs but is devoid
      of gross and acute toxicity.
AB  - BACKGROUND: All-trans-retinoyl beta-D-glucuronide, a water-soluble glucuronic
      acid conjugate of all-trans-retinoic acid, has demonstrated high biological
      activity and low toxicity in most in vitro and in vivo models. Since the
      reparative effects of retinoids on epithelium are well-known, our aim was to
      study the effect(s) of intravenously-administered all-trans-retinoyl beta-D
      glucuronide in lambs with chronic bacterial bronchopneumonia. MATERIAL/METHODS:
      Two groups of lambs were inoculated intrabronchially with either pyrogen-free
      saline or Mannheimia haemolytica. Thirty-three days later, lambs were injected
      four times at five-day intervals with 2 mL of 116 mM all-trans-retinoyl beta-D
      glucuronide (6.0-9.3 mmol/kg or 2.86-4.42 mg/kg animal body weight) in dimethyl
      sulfoxide, or dimethyl sulfoxide alone. Animal behavior and signs of clinical
      illness were logged daily. Lung and liver samples were assessed for
      histopathology, while serum and liver samples were extracted for retinoids and
      analyzed by reversed-phase gradient high-performance liquid chromatography.
      RESULTS: Repeated injections of highly concentrated all-trans-retinoyl beta-D
      glucuronide did not cause changes in appetite, activity or other behaviors nor
      did it cause histologic lesions in liver and lung. However, it had no effect on
      resolution of lung lesions resultant of chronic Mannheimia haemolytica
      bronchopneumonia. CONCLUSIONS: Repeated intravenous administration of high
      amounts of all-trans-retinoyl beta-D-glucuronide to lambs did not elicit signs of
      gross or microscopic toxicity. However, administering all-trans-retinoyl beta-D
      glucuronide too late in the progression of bacterial pneumonia is thought to be
      the main reason for its lack of effect in this model. A retinoid lactone
      derivative was detected in sheep serum and liver several days after treatment.

PMID- 12218936
TI  - Differences in the effects of haloperidol and clozapine on brain serotonin and
      dopamine metabolism and on tests related to extrapyramidal functions in rats.
AB  - BACKGROUND: An important goal of current neuroleptic research is to develop
      antipsychotic compounds with a low incidence of extrapyramidal side effects
      (EPS). Clozapine, the first of the atypical antipsychotics to be proven effective
      in treatment-resistant schizophrenia, is reported to produce less EPS than
      typical neuroleptics, such as haloperidol. MATERIAL/METHODS: The present study
      compares the neurochemical profiles of clozapine and haloperidol in rats. Animals
      injected (i.p.) with haloperidol or clozapine were sacrificed 1h later to collect
      brain samples. Neurochemical estimations were carried out by HPLC-EC. RESULTS:
      Administration of haloperidol at doses of 1.0, 2.5 and 5.0 mg/kg increased the
      concentration of homovanillic acid (HVA), a metabolite of dopamine (DA), in the
      striatum and rest of the brain. Clozapine-injected rats (2.5, 5.0 and 10.0 mg/kg)
      showed smaller increases in the striatum, but not in the rest of the brain.
      Dihydroxyphenylacetic acid (DOPAC), another DA metabolite not affected by
      haloperidol, increased in the striatum and decreased in the rest of the brain of
      clozapine-injected rats. 5-Hydroxyindoleacetic acid, the predominant metabolite
      of serotonin, increased with haloperidol and decreased with clozapine. A high
      dose of haloperidol (5.0 mg/kg) increased DA and 5-HT, while an equivalent does
      of clozapine (10.0 mg/kg) decreased levels in the rest of the brain. The effects
      of both drugs on the HVA/5-HIAA and DOPAC/5-HIAA ratios were also different.
      CONCLUSIONS: The differing activities of the two drugs at DA and serotonin
      receptors implies an important role for serotonin in treatment-resistant
      schizophrenia and a lower incidence of EPS.

PMID- 12218937
TI  - Ischemic preconditioning diminishes oxygen demand and increases coronary flow in
      the early phase of reperfusion in rat heart.
AB  - BACKGROUND: Ischemic preconditioning (IPC) can be defined as an adaptive
      mechanism induced by a brief period of reversible ischemia increasing the heart's
      resistance to a subsequent longer period of ischemia. The objective of our
      research was to describe the effects of IPC on the hemodynamic function and
      metabolism of the myocardium during postischemic reperfusion. MATERIAL/METHODS:
      20 rat hearts were assigned to a preconditioning group (n=10) or to a control
      group (n=10). Preconditioning was achieved with 5 min. of global ischemia and 10
      min. of reperfusion followed by 40 min. of ischemia. We investigated the
      postischemic recovery of aortic pressure, cardiac output, and coronary flow, as
      well as oxygen consumption, carbon dioxide release, and [H+] release. RESULTS: No
      significant intergroup differences in aortic pressure and cardiac output were
      observed during reperfusion. In both groups, increased coronary flow (greater in
      the IPC group: 11.4+/-0.6 ml/min. vs 9.1+/-0.5 ml/min. in control group) was
      observed in the early phase of reperfusion. This was accompanied by a rise in CO2
      and [H+] release, which was also greater in the IPC group. Oxygen consumption was
      significantly lower in the IPC group in the later phase of reperfusion (9.39+/
      0.53 vs 11.79+/-0.54 micromol/min/g dry weight), as were CO2 and [H+] release.
      CONCLUSIONS: IPC diminishes oxygen demand during reperfusion without changing the
      hemodynamic function considerably. IPC results in a transient increase of
      coronary flow accompanied by a rise in CO2 and [H+] release.

PMID- 12218938
TI  - CFTR gene mutations in patients suffering from acute pancreatitis.
AB  - BACKGROUND: The aim of our study was to investigate the frequency of the CFTR
      gene mutation in a selected group of patients suffering from severe acute
      pancreatitis. MATERIAL/METHODS: DNA isolated from peripheral blood samples from
      forty-one subjects was analyzed for the eight most common CFTR gene mutations
      (deltaF508, G542X, G551D, R553X, 1717-1(G>A), W1282X, N1303K, deltaI507) by the
      reverse-hybridization technique, using INNO-LIPA CF2 test strips. The level of
      chloride ions in sweat samples was established using the pilocarpine
      iontophoresis method. RESULTS: In the study group, none of the patients harbored
      CFTR gene mutations. In these selected cases, the experiments were repeated twice
      to ensure the reliability of the results. All of the subjects had a normal level
      of chloride ions (range 8-38 mmol/l). Comparison with historical carriers
      revealed no differences between the frequency of carriers of the CFTR gene
      mutations in the general Polish population (4%) in comparison with the surgical
      patients with acute pancreatitis (p=0.26; Fisher exact test). CONCLUSIONS: We
      found no patients with severe acute pancreatitis who had CFTR gene mutations,
      suggesting that these alterations are not a risk factor for the disease in our
      population. Further studies are warranted to evaluate the frequency and role of
      rare ('mild') CFTR gene point mutations in subjects suffering from severe acute
      pancreatitis.

PMID- 12218939
TI  - Cytotoxic effect of cyclosporin A alone and in combination with 2
      chlorodeoxyadenosine against P388 murine leukemia in vivo.
AB  - BACKGROUND: The purpose of our study was to determine the antileukemic effects of
      cyclosporin A (CsA) and its interaction with a new purine analogue, 2
      chlorodeoxyadenosine (2-CdA, cladribine) on P388 murine leukemia in vivo.
      MATERIAL/METHODS: Mice were engrafted intraperitoneally (i.p.) with 106 P388
      leukemia cells on day 0 of each step of the two-step experiment. All treatments
      were initiated on the next day (day 1) as daily i.p. injections and lasted for
      five consecutive days. In the first part of the experiment, designed to establish
      the antileukemic effect of CsA, the mice received 10, 15, 20, 25 or 30 mg/kg of
      CsA. In the second part, where the interaction between CsA and 2-CdA was
      examined, the animals were administered CsA at a dose of 15 mg/kg, or 2-CdA at a
      dose of 20 mg/kg, or CsA combined with 2-CdA at the same doses as in monotherapy.
      RESULTS: CsA did not influence the survival time of mice with P388 leukemia at
      any dose. CsA was used for the interaction study at a dosage of 15 mg/kg, as this
      was best tolerated by the animals. The mice treated with combination therapy
      using CsA and 2-CdA survived longer than those treated with 2-CdA monotherapy
      (p=0.00015). CONCLUSIONS: Our study revealed that CsA alone does not increase the
      survival time of mice with P388 leukemia, but it augments the antileukemic effect
      of 2CdA.

PMID- 12218940
TI  - Skin rubdown with a dry towel activates natural killer cells in bedridden old
      patients.
AB  - BACKGROUND: Skin rubdown using a dry towel to scrub the whole body is a
      traditional procedure. Because massage therapy is effective in improving cellular
      immunity, skin rubdown may also have the similar effects. MATERIAL/METHODS:
      Sixteen bedridden old patients, who had suffered a cerebral stroke, were studied.
      Skin rubdown for about 10 minutes was added for 10 days. Blood was collected at
      noon on the day before skin rubdown, 5 and 10 days after initiation and 5 days
      after completion, and the neutrophil count, lymphocyte count, serum gamma
      globulin and C-reactive protein (CRP) levels and natural killer cell activity
      were measured. In 9 of these 16 patients, B, T, CD4 and CD8 lymphocyte counts
      were additionally measured on the same days. RESULTS: There were no significant
      changes in the time course of the lymphocyte count, gamma-globulin or CRP levels.
      The neutrophil count increased 10 days after initiation of the skin rubdown, and
      natural killer cell activity increased 5 and 10 days after initiation, and
      returned to the baseline level 5 days after completion. Although there were no
      changes in the time course of the B, T, CD4 and CD8 lymphocyte counts, the
      CD4/CD8 ratio showed an increase 5 days after initiation and completion.
      CONCLUSIONS: Skin rubdown activates natural killer cells, which may be attributed
      to the effect of certain mediators released from the T lymphocytes and/or the
      stimulated effect on the sympathetic nerves. This technique may be used to reduce
      a variety of complications caused by the decreased immunity observed in bedridden
      old patients.

PMID- 12218941
TI  - Elevated plasma endothelin-1 levels and vascular dysregulation in patients with
      rheumatoid arthritis.
AB  - BACKGROUND: Contradictory results on plasma endothelin-1 (ET-1) levels in
      patients with rheumatoid arthritis have been reported in previous studies. We
      therefore evaluated whether plasma ET-1 levels in patients with rheumatoid
      arthritis differ from those of normal controls. Since systemically increased
      levels of ET-1 are known to occur in tandem with primary or secondary vascular
      dysregulation, we also measured peripheral blood flow by means of nailfold
      capillaroscopy combined with a cold provocation test. MATERIAL/METHODS: We
      measured plasma levels of ET-1 in twelve patients with different stages of
      rheumatoid arthritis by means of a specific radioimmunoassay, and compared ET-1
      values to those of healthy controls. Capillary blood flow and the frequency of
      cold-induced vasospasm were studied in parallel, using nailfold capillaroscopy
      combined with a cold provocation test. RESULTS: Plasma ET-1 levels were
      significantly increased in patients with rheumatoid arthritis (p = 0.01) when
      compared to controls (2.38+/-0.95 pg/ml vs. 1.53+/-0.38 pg/ml). Capillary blood
      flow was reduced when compared to our own normal values, and a cold-induced blood
      standstill was seen in 58% of the patients. CONCLUSIONS: Patients with rheumatoid
      arthritis exhibit significantly elevated levels of ET-1, which may be associated
      with the symptoms of vascular dysregulation observed in nailfold capillaroscopy.
      Even though the clinical conclusions should be drawn from this study with
      caution, additional therapy with calcium channel blockers or, possibly in the
      future, with ET-1 receptor blockers, may be beneficial in patients with
      rheumatoid arthritis.

PMID- 12218942
TI  - Resistance mutations in HIV-infected patients experiencing early failure with
      nelfinavir-containing triple combinations.
AB  - BACKGROUND: The purpose of our study was to assess the presence of nelfinavir
      (NFV)-associated resistance mutations at the time of early virological failure in
      subjects receiving NFV as part of a first protease inhibitor (PI)-based triple
      regimen. MATERIAL/METHODS: Subjects failing their first PI-based NFV-containing
      triple regimen were identified in six Spanish hospitals. HIV genotyping was
      carried out in plasma samples collected at the time of the first viral rebound.
      RESULTS: Upon initiation of NFV-based therapy, 19 of the 30 subjects (63%) were
      naive; 11 (37%) had been exposed to nucleoside analogues. Median HIV-RNA at the
      time of viral rebound was 4, 180 copies/ml. PCR-amplified products were obtained
      in 22 subjects (73%). These products were sequenced and primary PI resistance
      mutations were recognized in 6 patients (27%). All six individuals harbored the
      D30N mutation, and none presented the L90M mutation. Other PI resistance
      mutations were present in 5 subjects (at codons 36, 63, 71, 77, 82 and/or 88).
      Secondary PI resistance mutations were present in another 9 subjects. By
      contrast, mutations conferring resistance to reverse transcriptase inhibitors
      were present in 50% of the patients, and the M184V substitution was the most
      frequently seen. CONCLUSIONS: Nearly 75% of patients failing their first PI-based
      triple regimen containing NFV do not harbor PI resistance mutations. The D30N
      substitution, rather than L90M, is the most frequently recognized, which does not
      challenge the efficacy of further rescue interventions with other PIs. This
      observation supports the use of nelfinavir as first protease inhibitor.

PMID- 12218943
TI  - Detection and genotyping of astroviruses from children with acute gastroenteritis
      from Goiania, Goias, Brazil.
AB  - BACKGROUND: The astroviruses constitute important agents of childhood diarrhea.
      The purpose of our research was to detect and genotype astroviruses in fecal
      samples from children with acute gastroenteritis from Goiania- Goias, Brazil.
      MATERIAL/METHODS: The samples were collected from children up to five years of
      age with acute gastroenteritis, hospitalized in two public hospitals in Goiania-
      Goias, a city located in the West Central region of Brazil. A total of 516 fecal
      samples were collected from March 1998 to March 2000. These samples were first
      screened for rotavirus and adenovirus by an enzyme immunoassay (EIARA) and by
      PAGE for the detection of rotaviruses. In all samples negative for both viruses
      (n=351) the presence of astrovirus was investigated by reverse-transcription
      polymerase chain reaction (RT-PCR). RESULTS: 2.8% of the samples obtained from
      children up to two years of age were positive for astrovirus by RT-PCR, with an
      expected amplicon size of 449 bp. All positive samples, except one, were
      collected between October and December of 1998, which corresponds to the rainy
      season in the region (spring/early summer). Nested-PCR genotyping showed that all
      samples were genotyped and belonged to astrovirus genotype 1, presenting an
      amplicon band pattern of 212 bp. CONCLUSIONS: This study supports data from the
      literature about the occurrence of astrovirus in children with acute
      gastroenteritis. It also helps provide a better understanding of viral etiology
      in diarrhea.

PMID- 12218944
TI  - Physiological assessment of the function of the ileocecal junction with evidence
      of ileocecal junction reflexes.
AB  - BACKGROUND: The ileocecal junction (ICJ) appears to be a specialized segment of
      the gut which regulates the passage of the chyme from the ileum to the cecum. We
      investigated the response of the ICJ to cecal and ileal distension and the nature
      of this response (direct or reflex). MATERIAL/METHODS: Nine patients who had
      early cancer in the proximal transverse colon were studied during right
      hemicolectomy. The pressure response of the ICJ to cecal and ileal balloon
      distension was determined before and after cecal and ileal anesthesia. The
      balloon and manometric catheters were introduced into the cecum and ileum by
      colotomy and ileotomy, respectively. ICJ length was measured by the pull-through
      technique. RESULTS: The ICJ high pressure zone had a mean length of 3.6 cm. Chyme
      flow to the cecum occurred in jets. Large-volume cecal distension caused a
      significant rise in cecal and ICJ pressures and decreased ileal pressure; the
      balloon was dispelled to the transverse colon. Large-volume ileal distension
      caused an increase in ileal pressure, decreased ICJ and cecal pressures, and
      aboral balloon movement. No pressure response was produced by small volume
      distension or anesthesia of the cecum or ileum. CONCLUSIONS: Ileal distension is
      suggested to initiate reflex ICJ and cecal relaxation which is mediated through
      the 'ileocecal inhibitory reflex' and which allows the chime to pass to the
      cecum. Cecal distension appears to evoke reflex ileal and ICJ contraction, thus
      preventing ceco-ileal reflux and allowing time for chyme to accumulate in, and
      distend, the terminal ileum; we call this reflex the 'ceco-ileal excitatory
      reflex'. These 2 reflexes are thought to regulate chyme passage through the ICJ.

PMID- 12218945
TI  - Coronary artery anomalies in adult patients.
AB  - BACKGROUND: Coronary artery anomalies are discovered in less than 1% of
      angiography series. Since the number of angiographies and coronary bypass
      operations are increasing significantly every day, these anomalies are of
      clinical importance. MATERIAL/METHODS: 58,023 coronary angiographies were
      performed in the cardiology clinic of our hospital from 1978 to 2001. Coronary
      artery anomalies were discovered in 257 of these cases (0.44%). The mean age of
      these patients was 51.9+/-11.4 years (18-82). 80% were male (n=207). RESULTS: The
      circumflex artery (CXA) was the most frequently involved vessel (51.1%). Coronary
      arteries originating from the pulmonary artery were not encountered in our series
      due to the natural history of the disease. In 54 patients with coronary artery
      fistulae, 18 (33.3%) were closed by operation. Perioperative mortality was 5.5%.
      Acquired coronary artery fistulae or aneurysms due to trauma or inflammatory
      diseases are completely different entities and beyond the scope of this article.
      In 76 patients, open heart surgery was required for additional lesions, 57 of
      which were coronary artery bypass grafts. CONCLUSIONS: Being usually
      asymptomatic, coronary artery anomalies are usually discovered incidentally in
      the adult population. These pathologies are important for practical purposes,
      especially for interventional cardiologists, radiologists and cardiac surgeons,
      who should be aware of these anatomical entities. LMCA originating from the right
      coronary system has been reported to result in sudden death and myocardial
      ischemia, so these mostly asymptomatic patients must be followed closely.

PMID- 12218946
TI  - Borna Disease Virus--reactive antibodies in Polish psychiatric patients.
AB  - BACKGROUND: It has been proposed that the Borna Disease Virus (BDV) plays a role
      in the etiopathogenesis of psychiatric disorders. We assessed BDV seropositivity
      in Polish psychiatric patients and healthy controls, and the relationship between
      seropositivity and selected diagnostic and clinical variables. MATERIAL/METHODS:
      Serum samples from 946 psychiatric patients with different diagnoses (ICD-10) and
      407 psychiatrically healthy controls were assayed. The ECLIA method was used,
      which enables the assessment of two anti-BDV antibodies: anti-p24 and anti p-40.
      Data were also collected on diagnosis, age, age at onset, and place of residence.
      RESULTS: Only anti-p24 antibodies were found. The seropositivity rates were: 2.4%
      and 1.0%, respectively, in patients and controls (p=0.1). A significant
      difference between patients and controls was observed in mental retardation and
      affective-anxiety spectrum disorders. Seropositivity did not show any association
      with demographic variables, but it was elevated in patients with recent onset of
      disease vs. remote onset of disease (10.2% vs. 1.6%; p=0.0003). CONCLUSIONS:
      Significantly higher anti-BDV seropositivity was found in Polish psychiatric
      patients with affective-anxiety spectrum disorders and mental retardation than in
      controls. The association between recent onset disorders and higher anti-BDV
      response, in the light of recent reports on circulating immune complexes of BDV
      antigens and antibodies, warrants further studies on the longitudinal course of
      humoral response to BDV.

PMID- 12218947
TI  - Contemporary coronary intervention in bifurcation lesions--two-year follow-up in
      an unselected cohort.
AB  - BACKGROUND: Optimization of coronary angioplasty in bifurcation lesions remains a
      major challenge for percutaneous revascularization techniques. MATERIAL/METHODS:
      We evaluated procedural success, major in-hospital complications, target vessel
      revascularization, and 2-year clinical outcomes in 45 patients who underwent PTCA
      of a bifurcation lesion using currently available techniques and rigorous
      criteria for optimal immediate RESULTS: Angiographic success occurred in 100% of
      the parent vessels and in 84.4% of both vessels. Within the first 24 hours, there
      were no deaths or Q-wave myocardial infarction. Three non-Q-wave myocardial
      infarctions occurred (6.6%) and one emergency PTCA was necessary (2.2%).
      Therefore, clinical success was achieved in 91.2% of these patients. At 2-year
      follow-up, 3 cardiac deaths had occurred, the target revascularization rate was
      20%, and the total frequency of major adverse cardiac events (MACE) was 37.8%.
      CONCLUSIONS: Optimization of coronary angioplasty in bifurcation lesions is
      possible and results in a high angiographic success rate, low risk of acute
      complications and acceptable long-term clinical outcomes. However, the fairly
      high incidence of MACE at 2 years suggests that bifurcation lesions remain a
      challenge in everyday practice despite contemporary intervention methods and the
      use of GPIIb/IIIa inhibitors.

PMID- 12218948
TI  - Influence of the hepatocellular damage on the clinical usefulness of biochemical
      markers of bone metabolism and parathormon in haemodialysed patients.
AB  - BACKGROUND: The present study was undertaken to determine if hepatitis C virus
      (HCV) and cytomegalovirus (CMV) infections, as well as biochemical indices of
      liver damage, can significantly influence the relationships occurring between
      markers of bone formation, resorption and PTH in hemodialysis patients.
      MATERIAL/METHODS: 76 HD patients were tested for anti-HCV and anti-CMV
      antibodies. Serum intact PTH osteocalcin, total and bone isoenzyme of alkaline
      phosphatase, and plasma tartrate-resistant acid phosphatase were determined as
      bone metabolism indices. Serum alanine aminotransferase (ALT) and gamma-glutamyl
      transferase (gamma-GT) were measured as markers of hepatocyte function. The
      patients were divided into subgroups according to serological and enzymatic
      status. RESULTS: 37 patients were anti-HCV positive, 61 were anti-CMV positive,
      and 35 were both anti-HCV and anti-CMV positive. 13 patients were free of
      viruses. Elevated ALT and gamma-GT activity was found in 26 and 15 patients
      respectively. Indices of bone formation, resorption and PTH values showed no
      significance differences in the respective subgroups. Markers of bone formation
      significantly correlated with one another, as well as markers of bone resorption
      and intact PTH in all patients. In the subgroup of patients with increased gamma
      GT activity, significant differences were found in the slopes of the regression
      lines occurring in most of the estimated correlations in comparison with all
      other subgroups. CONCLUSIONS: In renal osteodystrophy, hepatocellular damage
      indicated by an increase of gamma-GT influences the relationship between the
      biochemical markers of bone metabolism and parathormon levels, but the presence
      of anti-HCV and anti-CMV antibodies does not.

PMID- 12218949
TI  - Heparin reduces oxidative stress in the postoperative period.
AB  - BACKGROUND: The purpose of our study was to investigate the influence of low-dose
      heparin on peroxide levels and the antioxidant activity of superoxide dysmutase
      (SOD), catalase (CAT), and glutathione peroxidase in the red blood cells of
      patients undergoing minor abdominal surgery. MATERIAL/METHODS: 49 patients
      scheduled for open cholecystectomy, with a median age of 43, were randomly
      assigned to either the heparin group (HG) or the placebo group (PG). HG patients
      received a subcutaneous dose of 100 IU/kg body weight of standard heparin for 6
      days, beginning the first day after surgery. On the day prior to surgery and on
      the 1st, 2nd and 6th postoperative days, blood samples from peripheral veins were
      collected, and the levels of peroxides, superoxide dysmutase (SOD), catalase
      (CAT) and glutathione peroxidase activity in the hemolysate of red blood cells
      were determined. The level of malondialdehyde was also measured. RESULTS:
      Significantly lower levels of peroxides, as well as higher antioxidant activity
      of SOD and CAT, was found in the erythrocytes of HG patients. Heparin
      administration did not significantly influence the activity of glutathione
      peroxidase. There were also no differences in the levels of malondialdehyde
      between HG and PG patients. CONCLUSIONS: Low-dose standard heparin administered
      subcutaneously in patients undergoing minor abdominal surgery shows an
      antioxidant effect. Further studies are required to clarify the mechanism of
      increased SOD and CAT activity in red blood cells induced by heparin.

PMID- 12218950
TI  - GI anthrax: report of one case confirmed with autopsy.
AB  - BACKGROUND: Bacillus Anthraces is a non-motile, rod like, gram-positive and
      aerobic bacillus that produces central oval-shaped spores and characterized by
      rough, irregular and often comma-shaped colonies in blood agar. About 95% of
      human anthrax is cutaneous and 5% respiratory. GI anthrax, a very rare type, has
      been reported in less than 1% of all cases. We thus report a case of GI anthrax
      with autopsy findings. CASE REPORT: A 15-year-old young adult man was admitted to
      our hospital with history of fever, abdominal pain and bloody diarrhea from 48
      hours after ingestion of half-cooked sheep's meat. In endoscopic exam of upper GI
      tract, the esophagus had been filled with fresh blood without any varices,
      stomach showed evidence of hemorrhage and had multiple erosion but no ulceration
      of duodenum. Penicillin G 24,000,000 U/day IV was started but unfortunately
      severe upper and lower GI hemorrhage developed, leading to hypotension and death.
      In autopsy, ascites, paraaortic and mesenteric lymphadenopathy was accident with
      some of them being hemorrhagic. The spleen was slightly enlarged with hemorrhagic
      congestion in some parts of it. In the blood sample drawn from the spleen, the
      filamentous bacillus was successfully found. CONCLUSIONS: Because of the fatal
      nature of the disease and the similarity of the signs and symptoms to the other
      gastrointestinal diseases, we should consider it as one of the probable
      differential diagnosis in the patients with upper and lower gastrointestinal
      bleeding with fever esp. in the endemic areas.

PMID- 12218951
TI  - AIDS research in developing countries: do the ends justify the means?
AB  - Concrete ethical standards for human research are clearly stipulated in both
      international and national codes of ethics, and are meant to protect human
      subjects, especially the most vulnerable. A recent clinical study conducted from
      1994 to 1997 by Dr. Thomas C, Quinn, M.D. has fueled the debate raging in the
      scientific community regarding the ethics of clinical AIDS research in developing
      countries. Quinn's conducted a community-based, randomized, controlled study of
      15,127 rural Ugandans to determine whether intermittent antibiotic treatment to
      reduce the prevalence of other sexually transmitted diseases would also reduce
      the rate of HIV transmission. Subsequently, the study identified 415 couples in
      which one partner was HIV positive and one was initially HIV negative and
      followed them prospectively for up to 30 months. Researchers were not permitted
      to inform the seronegative partner of the HIV status of the other partner. As a
      result, 90 of the initially HIV negative partners (21.7%) seroconverted during a
      follow-up period of 30 months. To allow for research studies in developing
      countries that are not permitted in the United States appears to make the Third
      World equivalent to a 'research sweat shop'. Developing nations offer easy access
      to patients, reduced costs, and less stringent regulations. This appears to
      create a double standard for medical research that is both ethically and humanly
      unacceptable, especially when other viable option exist. To allow relativism to
      seep into the international and national ethical standards will open the door to
      an idea that condones the possible abuse of those least able to protect
      themselves. Researchers have an ethical responsibility to uphold the integrity of
      these ethical standards. Failure to do so today may have a devastating impact on
      humanity in the future.

PMID- 12218952
TI  - Simultaneous virtual representation of both vascular and neural tissue within the
      subarachnoid space of the basal cistern--technical note.
AB  - BACKGROUND: The representation of different anatomical structures requires
      varying imaging modalities and protocols. By mental composition of single-slice
      images, a three-dimensional (3D) impression can be achieved. However, this
      presupposes an outstanding imagination and is subject to inaccuracies. The use of
      an interactive and multi-modal planning system which represents different data
      sets in one single virtual environment holds promise to facilitate and improve
      neurosurgical decision-making. The authors report the clinical application of a
      self-developed virtual planning system in a case of trigeminal neuralgia due to
      an ectatic basilar artery. MATERIAL/METHODS: We modified our virtual planning
      system (VIVENDI), to achieve a virtual representation of the basal cistern
      illustrating both vascular and neuronal information. After conducting several
      experiments to determine an appropriate scanning protocol, we matched the data
      achieved by magnetic resonance imaging (MRI) and magnetic resonance angiography
      (MRA). RESULTS: The system provides the vascular topography combined with
      information on the anatomical structure of the subarachnoid space. To illustrate
      the clinical usefulness of this planning approach, the authors present a case of
      trigeminal neuralgia caused by an ectatic basilar artery. Pre-operatively, the
      virtual representation returned accurate information on the anatomical
      configuration of the cerebellopontine angle and the course of the ectatic vessel.
      This information was confirmed during surgery. CONCLUSIONS: The presented case
      demonstrates the clinical applicability of VIVENDI within the subarachnoid space
      of the basal cistern. The virtual representation enables pre-operative planning
      and simulation based on the patient's individual anatomy.

PMID- 12218953
TI  - Thyrotropin receptor antibodies detected by the human recombinant TBII assay--a
      surrogate marker for autoimmune activity in Graves' ophthalmopathy?
AB  - BACKGROUND: Recently a new very sensitive and specific commercial method for
      detection of TSHR-Ab has become available: TBII assay using human recombinant
      TSHR. The aim of this study was to assess the potential of this novel TBII assay
      as a guideline for immunosuppressive therapy in patients with Graves'
      ophthalmopathy (GO). MATERIAL/METHODS: We detected serum TBII level in three
      groups of subjects: 17 patients with clinical symptoms of GO, 14 patients with
      Graves' disease without ophthalmopathy (Gd), and 13 healthy volunteers.
      Corticosteroid therapy consisted of intravenous infusions of methylprednisolone
      (MP) and subsequent treatment with oral prednisone (P). Serum samples were
      collected 24 hours before MP, 24 hours after MP, after 14 days of P treatment and
      after the end of corticosteroid therapy. RESULTS: The levels of TBII were
      significantly increased in both GO and Gd individuals as compared to the controls
      (p<0.001 and p<0.01 respectively). There was also a significant difference in
      serum TBII between GO and Gd patients (p<0.01). We observed elevated pretreatment
      TBII serum levels in corticosteroid-resistant individuals as compared to
      corticosteroid- responsive patients. Corticosteroids caused a significant
      decrease in TBII serum levels in GO patients. CONCLUSIONS: The lack of clinical
      improvement despite decreased TBII level in our study suggests that the humoral
      immune response is not crucial in the pathogenesis of early GO. However,
      measurement of TSHR-Ab by the novel h-TBII assay may have prognostic value in the
      treatment of patients with severe GO as a surrogate marker of autoimmune
      activity.

PMID- 12218954
TI  - Etoposide added to weekly leucovorin (LV)/5-fluorouracil (5-FU) in LV/5-FU pre
      treated patients with advanced colorectal cancer.
AB  - BACKGROUND: We evaluated the efficacy and safety of the weekly combination of
      etoposide, leucovorin (LV) and 5-fluorouracil (5-FU) when administered as second
      line chemotherapy in patients with relapsed/refractory advanced colorectal cancer
      (ACC), previously treated with weekly LV + 5-FU. MATERIAL/METHODS: Etoposide was
      administered at 3 different dose levels (DL), in 3 groups of patients (total=60):
      DL-I - etoposide 80 mg/m2, 45 min i.v. infusion, DL-II - etoposide 120 mg/m2, and
      DL-III - etoposide 180 mg/m2. In all three levels etoposide was followed by LV
      100 mg/m2 i.v., 1-hour infusion, and 5-FU 500 mg/m2 i.v. bolus. Treatment was
      administered until disease progression or unacceptable toxicity. RESULTS: No
      patients responded at DL-I, while 2 patients at DL-II and 3 at DL-III had a
      partial response (PR) (P<0.1). Two patients had stable disease (SD) at DL-I, 8 at
      DL-II, and 9 at DL-III (P<0.01). More patients progressed at DL-I (n=19) compared
      to DL-II (n=10) and DL-III (n=8) (p<0.0007). The time to progression was 17, 15,
      and 14 weeks, respectively, for DL-I, -II, and -III (P=0.9). Median survival was
      30, 30, and 32.5 weeks, respectively, for DL-I, -II, and -III (P= 0.27). Toxicity
      was mainly neutropenia, diarrhea and mucositis at all DLs, significantly more
      intense in DL-III. No difference was noticed in responses between DL-II and DL
      III, but toxicity in DL-III was more severe. CONCLUSIONS: The combination of
      etoposide with LV+5-FU has limited activity when administered after failure of
      weekly LV+5-FU in patients with ACC.

PMID- 12218955
TI  - Clinical and pharmacokinetic study of fractionated doses of oral etoposide in
      pediatric patients with advanced malignancies.
AB  - BACKGROUND: The purpose of this phase I study was to evaluate the toxicity
      profile, dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and plasma
      pharmacokinetics of oral etoposide, and to recommend a safe fractionated dose for
      phase II trials in pediatric patients with refractory solid tumors.
      MATERIAL/METHODS: All patients had tumors no longer amenable to established forms
      of treatment. The initial dose of etoposide was 20 mg/m(2) TID for 14 days every
      21 days (dose-level I). Etoposide plasma pharmacokinetics were studied on day 1
      of treatment and determined by HPLC. RESULTS: Seventeen children were enrolled,
      13 of whom were included in the pharmacokinetic study, for a total of 64 courses.
      Nine patients were included at dose-level I; grade 2-3 leucopenia was observed in
      5. The dose was then raised to 25 mg/m(2) (dose-level II) in another 8 patients;
      grade 3-4 leucopenia was observed in 4. This dose-level was therefore considered
      the MTD. The DLT was neutropenia. In patients at dose-level I and II the maximum
      plasma etoposide concentration was 2.97 and 8.59 mg/ml, respectively. Drug levels
      > 1 microg/ml were maintained for about 6.3 hours following drug administration
      at both dose-levels. Partial response was observed in 1 patient and 4 patients
      showed stable disease. CONCLUSIONS: Prolonged oral etoposide was well tolerated
      by our patients. Considering the MTD, and the fact that the patients included at
      dose-level I achieved an adequate (>1 microg/ml) plasma concentration of
      etoposide for a sufficient time, this dose level was recommended for phase II
      studies in pediatric malignancies.

PMID- 12218956
TI  - Effect of hormone replacement therapy with femoston on hemostasis in peri- and
      postmenopausal women.
AB  - BACKGROUND: Postmenopausal women are at increased risk of cardiovascular disease.
      Exogenous estrogens may potentially lower the risk of cardiovascular disease
      through beneficial changes in lipoprotein profile and hemostasis. The effect on
      the vascular system of combined estrogen/progestagen hormone replacement therapy
      is less clear. MATERIAL/METHODS: A group of 44 peri- and postmenopausal women was
      studied during treatment with Femoston, a sequentially combined hormone
      replacement therapy consisting of 17-beta-estradiol and dydrogesterone.
      Comparative analyses were made between the estrogen-only phase and the combined
      phase of the hormone replacement therapy. Comparisons were also made against the
      different phases of the spontaneous menstruation cycle in 10 pre- and
      perimenopausal controls. RESULTS: Femoston had a neutral effect on blood
      coagulation factors and had no effect on plasma glucose concentrations. With
      Femoston, there was a positive change in the atherogenic index and the total
      cholesterol/HDL cholesterol ratio. CONCLUSIONS: The findings from the present
      study provide evidence for the efficacy of Femoston hormone replacement therapy
      in terms of control of hemostasis and inducement of a potentially beneficial
      lipoprotein profile, which is important for reducing the risk of vascular
      pathology in peri- and postmenopausal women.

PMID- 12218957
TI  - Interaction of Helicobacter pylori (Hp) and nonsteroidal anti-inflammatory drugs
      (NSAID) on gastric mucosa and risk of ulcerations.
AB  - Hp and NSAID are the most common pathogens in the stomach, but their interaction
      on gastro-duodenal mucosa has been little studied. Hp infection in humans does
      not interfere with NSAID-induced gastric ulcer healing by omeprazole, therefore,
      there is no rationale to eradicate the germ. Hp infection induces COX-2
      expression resulting in excessive biosynthesis of gastroprotective prostaglandin
      (PG), which should in turn counteract NSAID-induced gastropathy and contribute to
      healing of existing ulcers. Some investigators claim that Hp infection acts
      synergistically with NSAID on ulcerogenesis and propose that Hp should be
      eradicated, particularly at the onset of long-term NSAID therapy. Our studies in
      about 6500 dyspeptic patients undergoing upper endoscopy and 13C-urea breath test
      revealed that about 70% of these patients are Hp positive and 31% of these
      develop gastro-duodenal ulcers. Of these ulcers, 66% were Hp positive and NSAID
      negative, 3%--NSAID positive and Hp negative, 8% were both Hp positive and NSAID
      positive, while 23% ulcers were Hp and NSAID negative. An evidence was obtained
      for negative interaction between Hp infection and NSAID on risk of gastro
      duodenal ulcers suggesting that Hp may attenuate the peptic ulcerogenesis. Our
      results support the concept 1) the interaction between Hp infection and NSAID on
      gastro-duodenal ulcerations is antagonistic, 2) the Hp and NSAID are independent
      risk factors for peptic ulcerations in humans, 3) there is no need for the Hp
      eradication in NSAID-treated patients, and 4) the rate of ulcer complications
      (hemorrhage and perforation) remains constant despite the decrease in Hp and
      ulcer prevalence.

PMID- 12218958
TI  - Superoxide dismutase--applications and relevance to human diseases.
AB  - Reactive oxygen species, such as superoxide radicals, are thought to underlie the
      pathogenesis of various diseases. Almost 3 to 10% of the oxygen utilized by
      tissues is converted to its reactive intermediates, which impair the functioning
      of cells and tissues. Superoxide dismutase (SOD) catalyzes the conversion of
      single electron reduced species of molecular oxygen to hydrogen peroxide and
      oxygen. There are several classes of SOD that differ in their metal binding
      ability, distribution in different cell compartments, and sensitivity to various
      reagents. Among these, Cu, Zn superoxide dismutase (SOD1) is widely distributed
      and comprises 90% of the total SOD. This ubiquitous enzyme, which requires Cu and
      Zn for its activity, has great physiological significance and therapeutic
      potential. The present review describes the role of SODs, especially Cu, Zn SOD,
      in several diseases, such as familial amyotrophic lateral sclerosis (FALS),
      Parkinson's disease, Alzheimer's disease, dengue fever, cancer, Down's syndrome,
      cataract, and several neurological disorders. Mutations in the SOD1 gene cause a
      familial form of amyotrophic lateral sclerosis. The mechanism by which mutant
      SOD1 causes the degeneration of motor neurons is not well understood. Transgenic
      mice expressing multiple copies of FALS-mutant SOD1s develop an ALS-like motor
      neuron disease. Vacuolar degeneration of mitochondria has been identified as the
      main pathological feature associated with motor neuron death and paralysis in
      several lines of FALS-SOD1 mice. Various observations and conclusions linking
      mutant SOD1 and FALS are discussed in this review in detail.

PMID- 12218959
TI  - Biological rhythms and behavior--then and now.
AB  - BACKGROUND: Living matter has its own 'biological time': a set of rhythmic
      oscillations, paced by genes whose expression varies over regular cycles. The
      resulting chronomes, or time structures, are usually studied in living matter. A
      human chronome is preserved long after death in the structure of tooth enamel.
      This fossil record can be compared with contemporary enamel thus providing
      insight into an ancient biological rhythm, and consequently into behavior in pre
      historic civilizations. MATERIAL/METHODS: Eight adult 3rd molar teeth from human
      burials in Atacama oases of Northern Chile, dating from AD 400 to 900 and
      belonging to the pre-Hispanic San Pedro culture, were compared to 20 discarded
      contemporaneous teeth from Albuquerque, N. M. USA. Two adjacent, 100 mm thick
      ground sections from each tooth were examined using a stereoscopic dissecting
      microscope and polarized light. The intervals between consecutive brown striae of
      Retzius (TBS) and the width of the enamel were measured. We recorded the number
      of TBS and the number of Wilson's bands and calculated a ratio of enamel
      width/number of TBS for each section. We used ANOVA for statistical analysis and
      cosinor methodology for chronomics, time structure (chronome) mapping. RESULTS:
      The 'biological week' in the chronome (time structure) of ancient enamel, gauged
      by TBS, varied according to a multiseptan (multiple of seven) component faster
      than did the multiseptan of contemporaneous teeth (1/2.7 versus 1/4.6 biological
      weeks). CONCLUSIONS: Until now no human chronome has been isolated from
      fossilized structures. Our discovery indicates that behavior of ancient
      populations, such as rest and work spans, can be deduced to some extent after
      millennia.

PMID- 12218960
TI  - Can carotid endarterectomy improve metabolic status in patients with asymptomatic
      internal carotid artery flow lesion? Studies with localized in vivo proton
      magnetic resonance spectroscopy.
AB  - PURPOSE: Carotid endarterectomy (CEA) has proven to be effective in the
      prevention of stroke in patients with significant internal carotid artery (ICA)
      stenosis. However, whether increased cerebral blood flow after CEA improves the
      cerebral metabolism in patients with asymptomatic ICA flow lesions is unknown.
      Localized in vivo proton magnetic resonance spectroscopy ((1)H-MRS) has been used
      to measure the metabolic status of the human brain in a totally noninvasive
      manner. The aim of this study was to investigate the cerebral metabolism after
      CEA in patients with asymptomatic ICA flow lesions and no visible infarction on
      magnetic resonance imaging (MRI). MATERIALS AND METHODS: We designed a
      prospective study to investigate the metabolic changes in the middle cerebral
      artery (MCA) territory with (1)H-MRS for 18 consecutive patients with
      asymptomatic severe stenosis of the ICA (>70% reduction in diameter) and for 16
      healthy control subjects. The 18 patients with ICA flow lesion and no visible
      infarction on MRI who underwent CEA were evaluated before and 7 days after
      surgery (CEA group). The 16 control subjects had never had a cerebral event, and
      brain MRI and carotid duplex scan study results were normal in all (control
      group). RESULTS: Preoperative ICA volume flow was severely decreased to less than
      150 mL/min in all 18 patients, in comparison with our laboratory normal value of
      matched age group of 250 to 300 mL/min. After CEA, ICA volume flow was increased
      to greater than 300 mL/min in all patients (P =.00). For patients in the CEA
      group, preoperative N-acetylaspartate/creatine and choline/creatine ratios in the
      MCA territory were slightly decreased compared with the healthy subjects in the
      control group but were within normal limits. However, the postoperative values of
      N-acetylaspartate/creatine and choline/creatine ratios in the ipsilateral MCA
      territory were significantly increased as compared with the preoperative values
      (P <.05). In the contralateral side, the postoperative increase of
      choline/creatine ratio and the decrease of myo-inositol/creatine ratio were
      statistically significant as compared with the preoperative values (P <.05).
      CONCLUSION: CEA seems to improve the cerebral metabolic status in patients with
      asymptomatic ICA flow lesions and no visible infarction on MRI.

PMID- 12218961
TI  - Effect of intraluminal thrombus on wall stress in patient-specific models of
      abdominal aortic aneurysm.
AB  - PURPOSE: The role of intraluminal thrombus (ILT) on abdominal aortic aneurysm
      rupture is still not clear. Rupture of an aneurysm occurs when the wall stress
      exceeds the wall strength at any location on the wall. The purpose of this study
      was to address the hypothesis that the presence of ILT alters the wall stress
      distribution or wall stress magnitude in AAA. METHODS: Patient-specific 3D AAA
      geometries were reconstructed from computed tomographic images. Two geometric
      features, ILT surface ratio (ILT surface area divided by the total AAA surface
      area) and ILT volume ratio (ILT volume divided by the total AAA volume), were
      calculated for each AAA. Two models were created for each patient: one with ILT
      and one without ILT. Systolic pressure measured at the time of computed
      tomographic imaging was applied to the internal surface of each model. A
      nonlinear large deformation algorithm was used to compute wall stress
      distribution with the finite element method. The Wilcoxon matched pairs test was
      used to compare the peak wall stress between the two models of each patient.
      RESULTS: Four patients were studied with ILT surface ratios that ranged from 0.29
      to 0.72 and ILT volume ratios that ranged from 0.12 to 0.66. The peak wall stress
      was reduced (range, 6% to 38% reduction; P =.067) for all models with ILT
      included (range, 28 to 37 N/cm(2)) as compared with models with no ILT (range, 30
      to 44 N/cm(2)). Visual inspection also revealed a marked effect of ILT on the
      wall stress distribution. CONCLUSION: The presence of ILT alters the wall stress
      distribution and reduces the peak wall stress in AAA. For this reason, ILT should
      be included in all patient-specific models of AAA for evaluation of AAA wall
      stresses.

PMID- 12218962
TI  - Prospective controlled study of the natural history of asymptomatic 60% to 69%
      carotid stenosis according to ultrasonic plaque morphology.
AB  - BACKGROUND/PURPOSE: In spite of the conclusions of the Asymptomatic Carotid
      Atherosclerosis Study, some clinicians are still reluctant to recommend carotid
      endarterectomy (CEA) for patients with asymptomatic > or = 60% carotid stenosis
      (ACS). This study analyzes the natural history of 60% to 69% ACS according to
      ultrasonic plaque morphology and its implication on treatment. PATIENT POPULATION
      AND METHODS: During a 2-year period, patients with 60% to 69% ACS entered into a
      protocol of carotid duplex scan surveillance/clinical examination every 6 months.
      The ultrasonic plaque morphology was classified as heterogeneous (group A, n =
      162) or homogeneous (group B, n = 229) with HDI 3000/HDI 5000 systems (Advanced
      Technology Laboratories, Bothwell, Wash). CEA was done if lesion progressed to >
      or = 70% stenosis or became symptomatic. RESULTS: Three hundred eighty-two
      patients (391 arteries) were followed for a mean interval of 37 months. The
      clinical/demographic characteristics were similar for both groups. The incidence
      rate of future ipsilateral strokes was significantly higher in group A than in
      group B: 13.6% versus 3.1% (P =.0001; odds ratio [OR], 5). Similarly, the
      incidence rate of all neurologic events (stroke or transient ischemic attack
      [TIA]) was higher in group A than in group B: 27.8% versus 6.6% (P =.0001; OR,
      5.5). Progression to > or = 70% stenosis was also higher in group A than in group
      B: 25.3% versus 6.1% (P =.0001; OR, 5.2). Forty-four late CEAs (27.2%) were done
      in group A (16 for stroke, 21 for TIA, and seven for > or = 70% ACS) versus 13
      (5.7%) in group B (five for stroke, seven for TIA, and one for > or = 70% ACS; P
      =.0001; OR, 6.2). CONCLUSION: Patients with 60% to 69% ACS with heterogeneous
      plaque had a higher incidence rate of late stroke, TIA, and progression to > or =
      70% stenosis than patients with homogeneous plaque. Prophylactic CEA for 60% to
      69% ACS may be justified if associated with heterogeneous plaque.

PMID- 12218964
TI  - Thirteen days in May.

PMID- 12218965
TI  - Prevalence of renovascular disease in the elderly: a population-based study.
AB  - PURPOSE: The purpose of this investigation was to estimate the population-based
      prevalence of renovascular disease (RVD), defined as > or = 60% diameter-reducing
      renal artery stenosis or occlusion, and to define its associations with age,
      gender, race, and other potential risk factors among participants in the
      Cardiovascular Health Study (CHS). METHODS: The CHS is a multicenter,
      longitudinal cohort study of cardiovascular disease risk factors, morbidity, and
      mortality among free-living adults of more than 65 years of age. As part of an
      ancillary investigation, participants in the Forsyth County cohort of the CHS
      were invited to undergo renal duplex sonography (RDS) to define the presence or
      absence of RVD. RVD was defined as stenosis with a focal renal artery peak
      systolic velocity exceeding 1.8 m/s in the main renal artery and defined as
      occlusion when an imaged renal artery lacked a Doppler signal. Demographic and
      atherosclerotic risk factor data were gathered as part of the baseline CHS
      examination. Univariable tests of association were performed with chi(2) and
      Student t tests and logistic regression analysis. Multivariate associations were
      examined with logistic regression analysis. RESULTS: Eight hundred seventy CHS
      participants underwent RDS. Of these examinations, 834 (96%) were technically
      adequate to define the presence or absence of RVD. The RDS study cohort had a
      mean age of 77.2 +/- 4.9 years and consisted of 63% women and 37% men.
      Participant race was 76% white and 23% African American. The overall prevalence
      rate of RVD was 6.8%. Among the 57 patients with RVD, 50 (88%) had unilateral
      disease and seven (12%) had bilateral disease. Seven cases were seen of renal
      artery occlusion, including one case with contralateral renal artery stenosis.
      The mean ages of patients with and without RVD were 78.7 +/- 5.7 years and 77.1
      +/- 4.9 years (P =.018). RVD was present in 5.5% of women and 9.1% of men (P
      =.053). RVD was present in 6.9% of white participants and 6.7% of African
      American participants (P =.933). Multivariate analysis revealed increasing
      participant age (P =.028; odds ratio, 1.34; 95% CI, 1.03, 1.73), high-density
      lipoprotein cholesterol levels of less than 40 mg/dL (P =.003; odds ratio, 2.63;
      95% CI, 1.40, 4.93), and increasing systolic blood pressure (P =.007; odds ratio,
      1.44; 95% CI, 1.10, 1.87) to be significantly and independently associated with
      the presence of RVD. CONCLUSION: This investigation provides the first population
      based estimate of the prevalence of RVD among free-living, elderly black and
      white Americans. RVD was present in 6.8% of the study cohort. RVD showed no
      association with ethnicity. However, its presence was significantly and
      independently associated with increasing age, low high-density lipoprotein
      cholesterol levels, and increasing systolic blood pressure.

PMID- 12218966
TI  - Prospective validation of an algorithm to maximize native arteriovenous fistulae
      for chronic hemodialysis access.
AB  - OBJECTIVE: The purpose of this study was to evaluate an algorithm to maximize
      native arteriovenous fistulae (AVF) for hemodialysis access. METHODS: The
      prospective study design was set in an academic, tertiary care medical center.
      The study subjects were adults referred for permanent, upper extremity
      hemodialysis access between April 1999 and May 2001. Intervention included
      Doppler arterial pressures/waveforms and duplex imaging of the basilic, cephalic,
      and central veins. The optimal configuration for an AVF was determined (criteria:
      vein >3 mm, no arterial inflow stenosis, no venous outflow stenosis) on the basis
      of the noninvasive studies, and unilateral arteriography/venography was performed
      to confirm the choice. Permanent hemodialysis access was created on the basis of
      the imaging studies, and remedial imaging/intervention was performed if the AVF
      failed to mature. Outcome measures included impact of the noninvasive/invasive
      imaging, perioperative morbidity/mortality, incidence of successful AVF, time to
      cannulation, and predictors of AVF failure with multivariate analysis. RESULTS: A
      total of 139 new access procedures was performed in 131 patients (age, 53 +/- 16
      years; male, 51%; white, 60%; diabetic, 49%; actively undergoing dialysis, 50%;
      prior permanent access, 26%). The noninvasive imaging showed that 83% of the
      patients were candidates for AVF, with a mean of 2.7 +/- 2.1 possible
      configurations. Invasive imaging was abnormal in 38% (forearm arterial disease >
      central vein stenosis > inflow stenosis) and impacted the operative plan in 19%.
      AVF were performed in 90% of the cases (brachiobasilic > brachiocephalic >
      radiocephalic > radiobasilic), with prosthetic AVF performed primarily because of
      inadequate veins. Among the patients who underwent AVF, the 30-day mortality rate
      was 1%, the complication rate was 20% (wound, 10%; hand ischemia, 8%), and 24%
      needed a remedial procedure. The AVF matured sufficiently for cannulation in 84%
      of those with sufficient follow-up and was suitable for cannulation by 3.4 +/-
      1.8 months. On the basis of an intention to treat approach, an AVF sufficient for
      cannulation developed in 71% of the 139 cases referred for access. The
      multivariate analysis predicted that female gender (odds ratio, 9.7; 95% CI, 2.2
      to 43.5) and the radiocephalic configuration (odds ratio, 4.6; 95% CI, 1.1 to
      18.6) were both independent predictors of failure of the fistula to mature.
      CONCLUSION: With the aggressive algorithm, the construction of native AVF is
      possible in the overwhelming majority of patients presenting for new hemodialysis
      access.

PMID- 12218967
TI  - Prediction of wrist arteriovenous fistula maturation with preoperative vein
      mapping with ultrasonography.
AB  - OBJECTIVE: The purpose of this study was to determine whether the preoperative
      minimal cephalic vein size in the forearm was predictive of successful wrist
      fistula maturation to a functional hemodialysis access. METHODS: Forty-four
      consecutive patients underwent evaluation before surgery with ultrasound scan
      imaging to map the entire cephalic vein in preparation for the construction of an
      arteriovenous fistula at the wrist. Measurements of the vein diameter were
      obtained from the ultrasound scan images at eight representative sites. Patients
      were clinically followed to determine maturation of the fistula to provide a
      functional hemodialysis access. The smallest diameter of the cephalic vein then
      was used as a preoperative predictor of fistula maturation. RESULTS: Successful
      maturation of the arteriovenous fistula was achieved in 22 of the procedures
      (50%). Cephalic veins with a minimal diameter of 2.0 mm or less were used for
      anastamosis in 19 patients (43%), and three of these procedures (16%) led to a
      functional access site. The remaining 25 patients (57%) had minimal cephalic vein
      diameters greater than 2.0 mm, producing a successful maturation in 19 of the
      fistula creations (76%). A significantly higher rate of successful fistula
      maturation in those patients with a preoperative minimal cephalic vein size
      greater than 2.0 mm was realized (P =.0002, chi(2) test, with Yates correction
      for continuity). CONCLUSION: In patients with a minimal cephalic vein size of 2.0
      mm or less, a procedure other than wrist fistula should be considered for
      optimization of dialysis access.

PMID- 12218968
TI  - The use of cryopreserved femoral vein grafts for hemodialysis access in patients
      at high risk for infection: a word of caution.
AB  - BACKGROUND: Several studies have reported success in the use of venous homografts
      for arteriovenous access and for arterial bypass in infected fields. On the basis
      of these reports and in an effort to prevent the loss of vascular access to
      infection, we performed arteriovenous graft placement with cryopreserved femoral
      vein in patients at high risk for graft infection. This study reviews the results
      of our experience. METHODS: Of approximately 3100 dialysis access operations
      performed in a single vascular surgery service between October 1999 and July
      2001, 20 patients received arteriovenous access grafts with cryopreserved femoral
      vein. All patients were judged to be at high risk for infection of the access on
      the basis of the presence of active infection at the time of graft implantation,
      the location of the graft in the thigh position, or a history of multiple access
      infections. The grafts were placed in three locations: thigh (n = 14), upper
      extremity (n = 3), and chest wall (n = 3). RESULTS: No early operative deaths or
      graft thromboses were seen. There were three late deaths: two from cardiac
      disease and one from a graft-related complication. Thirteen major graft related
      complications (65%) occurred in the 20 patients. There were three generalized
      graft infections (15%) and eight localized graft infections (40%) at dialysis
      needle access sites in 11 patients. Six of the graft infections were associated
      with graft rupture and frank hemorrhage, resulting in one patient death from
      exsanguination. Two grafts (10%) thrombosed, one of which was salvaged after
      thrombectomy and revision. These complications occurred between 1 and 14 months
      after implantation. At a mean follow-up period of 13 months (range, 1 to 17
      months), only five of the 20 patients (25%) have a functioning cryopreserved
      femoral vein arteriovenous graft. CONCLUSION: The use of cryopreserved vein graft
      for hemodialysis access in patients at high risk for infection is associated with
      a high incidence rate of graft infection and rupture, particularly when placed in
      the thigh position. The routine use of cryopreserved vein graft in the thigh
      should be avoided. The in situ replacement of infected polytetrafluoroethylene
      arteriovenous grafts with cryopreserved vein should be considered if alternative
      sites for new access placement are unavailable.

PMID- 12218969
TI  - Thoracoabdominal and descending thoracic aortic aneurysm surgery in patients aged
      79 years or older.
AB  - OBJECTIVE: Advanced age has been reported as a predictor of increased morbidity
      and mortality in patients who undergo major cardiovascular reconstructive
      surgery. In this study, we evaluated the outcome of patients aged 79 years or
      older after thoracoabdominal and descending thoracic aortic aneurysm repair.
      METHODS: From February 1991 to May 2001, 854 patients underwent operation for
      thoracoabdominal or descending thoracic aortic aneurysm. Fifty-six patients were
      between the ages of 79 and 88 years at the time of surgery, and these patients
      were included in this study. Risk factors were analyzed for their impact on
      mortality and morbidity in these elderly patients with univariate analysis.
      RESULTS: In patients at low risk, the 30-day mortality rate was 7/42 (17%),
      compared with 7/14 (50%) in patients at high risk with emergency presentation,
      congestive heart failure, or diabetes (P <.03). Four patients (7%; 4/56) had
      neurologic deficits develop. No single preoperative risk factor was significantly
      associated with increased mortality or neurologic deficits. CONCLUSION:
      Thoracoabdominal and descending thoracic aortic aneurysm repair in elderly
      patients can be undertaken with acceptable mortality and morbidity, provided that
      patients are selected appropriately.

PMID- 12218970
TI  - Endograft migration one to four years after endovascular abdominal aortic
      aneurysm repair with the AneuRx device: a cautionary note.
AB  - BACKGROUND: Positional stability of the endograft is essential for long-term
      durability after endovascular abdominal aortic aneurysm repair (EAR). However,
      the cumulative risk of delayed endograft migration has been sparsely reported.
      METHOD: A total of 91 patients studied underwent EAR with the AneuRx endograft
      with a minimum 1 year from implantation. Data from a prospective database were
      assessed for proximal endograft migration, defined as > or = 5 mm change from the
      initial endograft position. Multiple anatomic characteristics were also examined.
      Sixty-nine patients were alive, with complete follow-up at 1 year, with a mean
      time from implantation of 33.2 +/- 1.1 months. Data are mean +/- SEM. RESULTS:
      Endograft migration occurred in 15 patients, giving a cumulative event rate of
      7.2% (5/69) at 1 year, 20.4% (10/49) at 2 years, 42.1% (8/19) at 3 years, and
      66.7% (2/3) at 4 years post-EAR (P =.01). Although the initial aortic neck
      diameter did not differ between the groups (21.5 +/- 0.6 mm vs 21.8 +/- 0.3 mm, P
      =.61), significant (P <.05), late aortic neck enlargement was seen in patients
      with migration (25.0 +/- 1.6 mm, 26.2 +/- 1.2 mm, and 27.0 +/- 1.0 mm at 1,2, and
      3 years, respectively) but not in nonmigrators. Regression analysis demonstrated
      a statistically significant (P <.05) correlation between endograft oversizing and
      late aortic neck dilation. Overall migration risk was 29.2% in patients oversized
      >20% and 18.6% in patients oversized < or = 20%. Aortic neck angulation (23.4 +/-
      6.6 degrees vs 23.5 +/- 3.3 degrees, P =.99), aortic neck length (25.9 +/- 2.5 mm
      vs 27.0 +/- 1.6 mm, P =.74), initial endograft/aortic neck overlap (18.6 +/- 2.6
      mm vs 19.4 +/- 1.4 mm, P =.80) and size of abdominal aortic aneurysm (55.5 +/-
      1.5 mm vs 54.9 +/- 1.4 mm, P =.84) were similar between migrators and
      nonmigrators, respectively. Secondary endovascular treatment with aortic cuffs
      was required in five patients with device migration. CONCLUSIONS: Device
      migration after EAR with the AneuRx endograft occurred with significant
      frequency, the incidence of which increased with the length of follow-up. Late
      aortic neck dilation was significantly associated with migration. Oversizing of
      the endograft of >20% may accelerate this late aortic neck dilation. However, the
      etiologies of endograft migration were likely multifactorial, as the majority
      (8/15) of patients experiencing migration were oversized <20%. Although
      endovascular repair of these migrations is usually possible, the long-term
      durability of these secondary procedures is unknown. Careful surveillance for
      this endograft failure mode must be an essential component of post-EAR follow-up.

PMID- 12218971
TI  - Mechanism of failure in the treatment of type II endoleak with percutaneous coil
      embolization.
AB  - PURPOSE: Type II endoleak after endovascular abdominal aortic aneurysm repair is
      a failure of aneurysm sac exclusion with unknown long-term consequences. Elevated
      aneurysm sac pressures documented in these patients have led us to aggressively
      treat type II endoleaks with percutaneous transluminal coil embolization (PTCE).
      The purpose of this study was to evaluate the results and the mechanisms of
      failure of PTCE for type II endoleak. METHODS: One hundred ninety-one patients
      underwent endograft repair of infrarenal aortic aneurysms. Twenty-three of 28
      patients with persistent primary (>3 months) or secondary (new-onset) endoleak
      underwent angiography; 14 of these patients had type II endoleaks. We reviewed
      our endovascular registry data, hospital charts, and radiologic studies of
      patients with type II endoleaks and analyzed the results in those treated with
      PTCE of the inflow vessel. RESULTS: All 14 patients with type II endoleaks were
      men, with a mean age of 76.7 years and a mean preoperative maximal aneurysm
      diameter of 5.7 +/- 1.0 cm. The type II endoleak was primary in 12 patients (86%)
      and secondary in two patients (14%) and iliolumbar in 11 patients (78%) and
      mesenteric in three patients (21%). Although a dominant affluent collateral
      channel (inosculation) was apparent in eight patients (57%), six patients (43%)
      showed a network of collateral vessels (retiform anastomosis). In six patients
      (43%), angiography revealed a second or "outflow" vessel indicative of a complex
      endoleak. In four patients with retiform iliolumbar type II endoleaks, PTCE was
      not attempted because of the retiform nature of the endoleak. The remaining 10
      patients underwent PTCE, with coil deployment in all 10 and apparent initial
      technical success in nine patients. Follow-up computed tomographic scans revealed
      persistent endoleaks in six patients (60%). Mechanisms of failure included
      persistent flow through the coils in the treated vessel in two patients,
      development of a retiform anastomosis around the coiled vessel in three patients,
      and development of a new mesenteric endoleak after successful occlusion of an
      iliolumbar endoleak in one patient. Two patients underwent repeat PTCE with
      successful aneurysm sac exclusion in one. Internal iliac artery injury
      complicated one of the 12 PTCEs, and the resulting pseudoaneurysm was
      successfully treated with PTCE. Angiographic visualization of an outflow vessel
      (complex endoleak) was associated with PTCE failure (P =.008). CONCLUSION: PTCE
      of type II endoleaks has a high failure rate because of multiple anatomic
      mechanisms.

PMID- 12218972
TI  - Analysis of medical risk factors and outcomes in patients undergoing open versus
      endovascular abdominal aortic aneurysm repair.
AB  - OBJECTIVE: The emergence of endovascular repair (ER) for infrarenal abdominal
      aortic aneurysm (AAA) has provided surgeons with a new technique that should
      ideally improve patient outcomes. To more accurately characterize the advantages
      of ER versus traditional/open AAA repair (TOR), we compared the preoperative
      medical risk factors (PMRFs) and perioperative outcomes (PO) of those patients
      undergoing elective treatment of infrarenal AAA with ER and TOR over a recent 18
      month period at our center. METHODS: Through our institutional vascular surgery
      patient registry, all patients undergoing aortic aneurysm repair of any type
      between December 1999 and June 2001 were identified. Only those patients
      undergoing elective infrarenal AAA repair were analyzed. Hospital records were
      examined for all patients, and PMRF and PO were assessed via Society for Vascular
      Surgery/International Society for Cardiovascular Surgery reporting guidelines.
      Student t, chi(2), Fisher exact, or Wilcoxon rank sum tests were applied where
      appropriate to determine differences among PMRF and PO according to method of
      aneurysm repair. RESULTS: During the 18-month study period, a total of 199 aortic
      aneurysms were repaired at our institution. Ninety-nine elective infrarenal AAA
      repairs made up the study cohort (ER, n = 33; TOR, n = 66). When examined by
      method of aneurysm repair, no differences existed in demographics or AAA size.
      Patients undergoing ER had a significantly greater degree of preoperative
      pulmonary comorbidity than patients undergoing TOR (P <.001). However, no
      differences existed in terms of American Society of Anesthesiologists
      classification or cardiac (P =.52), cerebrovascular (P =.44), diabetic (P =.51),
      hypertensive (P =.90), hyperlipidemia (P =.91) or renal (P =.23) comorbidities
      between the two groups. Perioperative morbidity and mortality rates were also not
      significantly different by method of repair. ER was associated with shorter
      operative time, intensive care unit stay, and overall hospital length of stay (P
      <.0001). However, subsequent operative procedures related to the AAA repair were
      performed more frequently after ER (TOR = 1.5% versus ER = 15.2%; P = 0.015).
      CONCLUSION: These results suggest that ER offers improvements in hospital
      convalescent and operating room times but no beneficial impact on overall
      morbidity and mortality rates when similar PMRFs exist, especially when used at
      medical centers where low morbidity and mortality rates are already established
      for TOR. Other centers performing ER should undertake such an analysis to assess
      its impact on their patients.

PMID- 12218973
TI  - A prospective evaluation of hypogastric artery embolization in endovascular
      aortoiliac aneurysm repair.
AB  - PURPOSE: Hypogastric artery embolization (HAE) is often performed in endovascular
      aortoiliac aneurysm repair to prevent potential endoleak, and this can be
      associated with pelvic ischemic sequelae. This prospective study was performed to
      evaluate the clinical outcome of HAE in patients who underwent endovascular
      aortoiliac aneurysm repair. METHODS: During a 15-month period, 12 patients who
      underwent either unilateral or bilateral HAE for endovascular aortoiliac aneurysm
      repair were prospectively evaluated. All patients underwent preoperative and
      postoperative penile pressure measurement and pulse-volume recording evaluation.
      Angiographic features relating to pelvic collaterals and clinical outcomes
      relating to pelvic ischemia were evaluated. RESULTS: Unilateral HAE was performed
      in eight patients (67%), and bilateral HAE was performed in four patients (33%).
      Mean reductions in penile brachial index (PBI) after unilateral and bilateral HAE
      were 13 +/- 6% (not significant) and 39 +/- 14% (P <.05), respectively. Erectile
      dysfunction occurred in three patients for unilateral HAE (38%) and in two
      patients for bilateral HAE (50%), with an overall PBI reduction of 36 +/- 12% (P
      <.01). No significant change in thigh brachial or ankle brachial index occurred
      after HAE. Hip and buttock claudication occurred in four patients for unilateral
      HAE (50%) and in two patients for bilateral HAE (50%), with an overall PBI
      reduction of 18 +/- 9% (P <.05). Other associated pelvic ischemic complications
      after bilateral HAE included one scrotal skin sloughing (25%) that occurred 3
      days after aortic endografting and one sacral decubitus (25%) that occurred 4
      months after aortic endografting. With analysis of angiographic collateral
      patterns, diseased profunda femoral artery (PFA; >50% stenosis) was noted in four
      patients, all in whom post-HAE pelvic ischemic symptoms developed (P <.05). In
      contrast, only four of the remaining eight patients with normal or mild PFA
      disease had pelvic ischemic sequelae after HAE. CONCLUSION: Erectile dysfunction
      after HAE correlates with significant reduction in PBI. Severe pelvic ischemic
      symptoms are more likely to occur after bilateral HAE, which should be avoided if
      possible. Moreover, patients with diseased PFA are at risk of development of
      pelvic ischemia after HAE. Our data suggest a potential role of concomitant
      profundapalsty at the time of aortic endografting to improve pelvic collateral
      flow and reduce pelvic ischemia in this subset of patients with HAE.

PMID- 12218974
TI  - Predictors for adverse outcome after iliac angioplasty and stenting for limb
      threatening ischemia.
AB  - OBJECTIVE: The role of iliac artery angioplasty and stenting (IAS) for the
      treatment of limb-threatening ischemia is not defined. IAS has been used
      primarily for patients with disabling claudication. Because poorer results have
      been shown in patients with critical ischemia after iliac artery angioplasty, the
      purpose of this study was to estimate the influence of risk factors on the
      outcome of iliac angioplasty and stent placement in patients with limb
      threatening ischemia. METHODS: During a 5-year period (from 1996 to 2001), 85
      iliac angioplasty and stent placement procedures (107 stents) were performed in
      31 women and 43 men with limb-threatening ischemia. Patients with claudication
      were specifically excluded. The criteria prepared by the Ad Hoc Committee on
      Reporting Standards (Society for Vascular Surgery/International Society for
      Cardiovascular Surgery) were followed to define the variables. The TransAtlantic
      InterSociety Consensus classification was used to characterize the type of iliac
      lesions. Both univariate (Kaplan-Meier [KM]) and multivariate analyses (Cox
      proportional hazards model) were used to determine the association between
      variables, cumulative patency, limb salvage, and survival. RESULTS: Indications
      for iliac angioplasty with stenting were ischemic rest pain (56%) and tissue loss
      (44%). Primary stenting was performed in 36 patients (42%). Stents were placed
      selectively after iliac angioplasty mainly for residual stenosis or pressure
      gradient (43%). Overall, primary stent patency rate was 90% at 1 year, 74% at 3
      years, and 69% at 5 years. Primary stent patency rate was significantly reduced
      in women compared with men (KM, log-rank test, P <.001). Primary patency rates at
      1, 3, and 5 years were 79%, 57%, and 38% for women and 92%, 88%, and 88% for men.
      Primary stent patency rate also was significantly reduced in patients with renal
      insufficiency (creatinine level, >1.6 mg/dL; KM, log-rank test, P <.001). Cox
      regression analysis identified female gender (relative risk, 5.1; 95% CI, 1.8 to
      7.9; P =.002) and renal insufficiency (relative risk, 6.6; 95% CI, 1.6 to 14.2; P
      =.01) as independent predictors of decreased primary stent patency. No
      independent predictors for limb salvage and survival were identified. CONCLUSION:
      Women undergoing iliac angioplasty and stenting for limb-threatening ischemia
      have significantly reduced primary stent patency rates and may need additional
      procedures to obtain satisfactory clinical improvement and limb salvage. Patients
      with renal insufficiency and critical ischemia also have reduced primary stent
      patency rates after IAS. Limb salvage, as shown in this study, is not affected by
      previous iliac stent failure.

PMID- 12218975
TI  - Has endovascular surgery reduced the number of open vascular operations performed
      by an established surgical practice?
AB  - OBJECTIVE: Driven by new technology and the trend toward minimally invasive
      techniques, vascular surgeons have eagerly begun performing catheter-based
      arterial interventional procedures, a subspecialty termed endovascular surgery.
      How incorporation of endovascular surgery by vascular surgeons has influenced the
      number of standard open peripheral vascular operations is unknown. The purpose of
      this observational study was to examine the effect of endovascular surgery
      performed by the vascular surgeons of an established vascular surgery service on
      the volume of open peripheral vascular operations performed. METHODS: With our
      prospective vascular registry, we compared the number of index vascular
      procedures from 1996 to 1998 (immediately before the start of an endovascular
      program) with the numbers from 1999 to 2000 (immediately after the start of an
      endovascular program). Differences in proportions (endovascular versus
      open/standard) between the two time periods were compared with the chi(2) test
      for homogeneity. RESULTS: From 1996 to 1998, 122 procedures were referred to
      radiology for arterial intervention versus none from 1999 to 2000, reflecting the
      initiation of the endovascular program. During the entire study period, annual
      volume (endovascular + open/standard) of vascular procedures, excluding the
      procedures referred to radiology, increased by 70% (1996, n = 402; to 2000, n =
      685). Although open procedures from 1996 to 1999 increased 49% (n = 356 to n =
      531), the number decreased by 5% from 1999 to 2000 (n = 531 to n = 507). In
      contrast, the endovascular volume from 1996 to 2000 increased 324% (n = 42 to n =
      178). A statistically significant reduction was seen over time in the proportion
      of open/standard cases to endovascular cases in comparison of 1996 to 1998 with
      1999 to 2000 for total cases (n = 1539, 88% open; versus n = 1341, 77% open) and
      for all index procedures (aortoiliac, 70% versus 55%; abdominal aortic aneurysm,
      100% versus 63%; brachiocephalic, 73% versus 47%; renal, 60% versus 24%) except
      carotid procedures (100% versus 99%) and femoral-popliteal/tibial procedures (87%
      versus 87%). CONCLUSION: The integration of endovascular procedures by vascular
      surgeons of an established vascular practice significantly reduced the proportion
      of all open vascular procedures except for carotid and femoral-popliteal/tibial
      intervention. These data may have important implications for the future training
      of general and vascular surgeons.

PMID- 12218976
TI  - Chronic venous insufficiency: clinical and duplex correlations. The Edinburgh
      Vein Study of venous disorders in the general population.
AB  - OBJECTIVE: The objective of this study was to determine the prevalence of chronic
      venous insufficiency (CVI) in the general population and to correlate its
      clinical features with sonographically proven venous reflux. DESIGN OF STUDY: The
      study design was a cross-sectional survey of the general population. SUBJECTS AND
      METHOD: Ambulatory men and women, aged 18-64 years, were selected randomly from
      12 general practices. Subjects were examined for CVI. Eight segments of the deep
      and superficial veins were assessed for reflux by means of duplex scanning.
      RESULTS: A total of 1566 subjects were screened (867 women, mean age 44.8 years;
      699 men, mean age 45.8 years) of whom 124 were diagnosed as having CVI: 95, grade
      1; 19, grade 2; and 10, grade 3. The age-adjusted prevalence for the whole
      population was 9.4% in men and 6.6% in women. Prevalence of CVI correlated
      closely with age and sex, being 21.2% in men >50 years and 12.0% in women >50
      years. Heaviness and tension, and a feeling of swelling, aching, and itching,
      were significantly associated with worsening grade of CVI. CVI was significantly
      associated with reflux in all deep and superficial segments. The frequency of
      reflux in both superficial and deep segments increased with the clinical severity
      of disease. In 30.8% of subjects with CVI in the left leg, reflux was limited to
      the superficial system. CONCLUSIONS: The prevalence of CVI rises steeply with
      age. There is a strong correlation between venous symptoms and the presence and
      severity of CVI. CVI is associated in approximately one third of the subjects
      with incompetence limited to the superficial system and in these a good
      therapeutic outcome could be expected from surgery to the superficial veins. The
      severity of clinical features, including Basle CVI grade 1, correlates
      significantly with prevalence of valvular reflux in the deep and superficial
      systems. If leg ulcers are to be prevented by timely intervention, a better
      understanding of the natural history of the association between presenting
      features and disordered hemodynamics is required.

PMID- 12218977
TI  - Limitations in the cardiac risk reduction provided by coronary revascularization
      prior to elective vascular surgery.
AB  - OBJECTIVE: The objective of this study was to evaluate the proposed cardiac
      protective effect of previous coronary revascularization (coronary artery bypass
      grafting [CABG] or percutaneous transluminal coronary angioplasty [PTCA]) before
      elective major arterial surgery. METHOD: Preoperative cardiac risk stratification
      using American College of Cardiology/American Heart Association (ACC/AHA)
      guidelines was done on 425 consecutive patients undergoing 481 elective major
      vascular operations at an academic VA Medical Center. The algorithm assumed
      asymptomatic patients with prior coronary revascularization (CABG, <5 year; PTCA,
      <2 year) were low cardiac risk. Coronary angiography was done for recurrent
      symptoms with secondary intervention when appropriate. Outcomes (myocardial
      infarction, unstable angina, congestive heart failure, ventricular arrhythmia,
      cardiac death, and mortality) within 30 days of vascular surgery were compared
      between patients with and without previous CABG or PTCA by contingency table and
      logistic regression analyses. RESULTS: Coronary revascularization was classified
      as recent (CABG, <1 year; PTCA, <6 months) in 35 cases (7%), prior (1 year < or =
      CABG < 5 year, 6 months < or = PTCA < 2 year) in 45 cases (9%), and remote (CABG,
      > or = 5 year; PTCA, > or = 2 year) in 48 cases (10%). A larger fraction of
      patients with previous revascularization possessed pathologic cardiac risk
      variables and were stratified as high-risk preoperatively than their
      nonrevascularized counterparts. Outcomes in patients with previous PTCA were
      similar to those after CABG (P =.7). Significant differences in adverse cardiac
      events (P =.01) and mortality (P =.05) were found between patients with CABG done
      within 5 years or PTCA within 2 years (6.3%, 1.3%, respectively), individuals
      with remote revascularization (10.4%, 6.3%), and nonrevascularized patients
      stratified at high risk (13.3%, 3.3%) or intermediate/low (2.8%, 0.9%) risk. De
      novo or recurrent 3-vessel coronary disease by angiography, but not the presence
      or timing of previous revascularization, was an independent predictor of cardiac
      events after vascular operations, whereas remote revascularization was associated
      with fatal outcomes by multivariate analysis. CONCLUSIONS: Previous coronary
      revascularization (CABG, <5 years; PTCA, <2 years) may provide only modest
      protection against adverse cardiac events and mortality following major arterial
      reconstruction.

PMID- 12218978
TI  - Semiquantitative dipyridamole myocardial stress perfusion imaging for cardiac
      risk assessment before noncardiac vascular surgery: a meta-analysis.
AB  - BACKGROUND: Semiquantitative dipyridamole myocardial perfusion scintigraphy may
      provide better estimates of perioperative cardiac risk than nonquantitative
      scintigraphy. OBJECTIVE: The purpose of this study was to conduct a metaanalysis
      of semiquantitive dipyridamole myocardial perfusion scintigraphy for the
      prediction of perioperative myocardial infarction and cardiac death in patients
      undergoing noncardiac vascular surgery. METHODS: The data sources used were
      MEDLINE (from 1975 to 1999), citation lists, and correspondence with study
      authors. We included studies that evaluated preoperative semiquantitative
      dipyridamole myocardial perfusion scintigraphy in patients undergoing noncardiac
      vascular surgery. For each study, we calculated results on the basis of the
      proportion of myocardial segments with reversible perfusion defects. The
      complications of interest were cardiac death and nonfatal myocardial infarction.
      We calculated likelihood ratios (LRs) and areas under the receiver operating
      characteristic curves for individual studies and for the combined data. DATA
      SYNTHESIS: We identified nine studies involving a total of 1179 patients with 82
      cardiac complications (complication rate, 7.0%). Most studies were grade C in
      quality. Normal scans significantly reduced the likelihood of perioperative
      cardiac complications (LR, 0.42; 95% CI, 0.20 to 0.88). Fixed defects reduced the
      likelihood of complications, but the effect was not statistically significant
      (LR, 0.51; 95% CI, 0.24 to 1.1). Reversibility in less than 20% of myocardial
      segments did not change the likelihood of perioperative cardiac complications
      (LR, 1.3, 95% CI, 0.88 to 1.9). LRs for increasing extents of reversibility were:
      20% to 29% reversibility (LR, 1.6; 95% CI, 1.0 to 2.6), 30% to 39% reversibility
      (LR, 2.9; 95% CI, 1.6 to 5.1), 40% to 49% reversibility (LR, 2.9; 95% CI, 1.4 to
      6.2), and 50% or more reversibility (LR, 11; 95% CI, 5.8 to 20). The pooled area
      under the receiver operating characteristic curve was 0.78 (95% CI, 0.65 to
      0.89). Heterogeneity was found among study results, but exclusion of
      heterogeneous studies did not significantly change the summary results.
      CONCLUSION: Reversible defects in less than 20% of myocardial segments do not
      significantly alter the risk of perioperative cardiac complications. Greater
      extents of reversibility on dipyridamole myocardial stress perfusion imaging
      increase the risk of perioperative complications after noncardiac vascular
      surgery, but the quality and amount of data regarding greater extents of
      reversibility are limited.

PMID- 12218979
TI  - Medical management versus investigate-and-operate strategy in asymptomatic
      carotid stenosis: a decision analysis.
AB  - OBJECTIVE: The objective of this study was to determine whether asymptomatic
      patients at high risk for carotid stenosis should undergo screening Duplex
      ultrasound (DUS), with a view to offering carotid endarterectomy (CE) to those
      patients with significant stenosis. METHOD: We constructed a decision analysis
      model to evaluate the impact of an investigate-and-operate strategy, compared
      with medical management alone, on the risk of stroke in patients at high risk for
      carotid stenosis. We studied five investigate-and-operate models addressing
      different thresholds for intervention (in terms of degree of stenosis) and the
      effects of using or not using preoperative angiography. RESULTS: For each of the
      strategies, under the base case conditions (30% prevalence of >50% carotid
      stenosis), the number needed to screen (NNS) and the number needed to treat (NNT)
      are high (213 to 769 and 13 to 144, respectively). The strategy of angiography
      for >50% stenosis and CE for >70% stenosis was harmful. Other strategies were
      unattractive because of unacceptably high NNT (no angiography, CE >50% stenosis),
      or because of unacceptably high NNS (angiography >70%, CE >70% stenosis), or both
      (angiography >50% stenosis, CE >50% stenosis; no angiography, CE > 70% stenosis).
      At 50% prevalence of >50% stenosis, two models produced more reasonable
      combinations of NNT and NNS: 11 and 370, respectively, for angiography >70%, CE
      >70% stenosis; and 27 and 286, respectively, for no angiography, CE >70%
      stenosis. Within the range of clinically plausible values for sensitivity and
      specificity of DUS, results were not greatly influenced by the measurement
      properties of DUS. However, angiographic or surgical rates of stroke or death
      were critical to the outcomes with any strategy. Only 3% to 12% of strokes in the
      studied population were prevented. CONCLUSIONS: Screening is acceptable only in
      populations at >40% to 50% risk for >50% carotid stenosis, who are surgical
      candidates, and who would undergo surgery if recommended. Acceptable investigate
      and-operate strategies include angiography for DUS stenosis >70%, with CE if this
      level of stenosis is confirmed, and CE for DUS-measured stenosis >70% without
      angiographic confirmation. Surgery for asymptomatic carotid stenosis is unlikely
      to have a large impact upon the burden of stroke in society.

PMID- 12218980
TI  - Distal vertebral artery reconstruction: long-term outcome.
AB  - PURPOSE: The purpose of this article was to report our long-term results of
      distal vertebral artery (DVA) reconstruction. METHOD: From 1978 to 2001 we
      performed 352 DVA reconstructions on 323 patients (177 men, 148 women; mean age,
      60.0 +/- 12.1 years). Symptoms of vertebrobasilar insufficiency were present in
      332 cases (94.3%). Bypass grafting using mostly saphenous vein graft was
      performed in 240 cases (68.2%). In 102 cases (29.0%) the DVA was transposed into
      the internal carotid artery (ICA). Other techniques were used in 10 cases.
      RESULTS: Stroke caused all 7 deaths (2.0%) in the early postoperative period.
      There were 5 nonfatal strokes (1.4%). Strokes were hemispheric in 7 cases (6
      ipsilateral, 1 contralateral) and vertebrobasilar in 5 cases. There were 6
      strokes (2.3%) in the subgroup of 264 isolated DVA reconstruction and 6 strokes
      (6.8%) in the subgroup of 88 procedures involving combined ICA and DVA
      reconstruction (P <.04). Temporary paralysis of the spinal accessory nerve
      occurred in 26 cases (7.4%). Intraoperative or early postoperative angiography
      findings were available in 341 of 345 cases (98.8%). Early postoperative
      occlusion occurred after 25 procedures (7.1%). Complete clinical follow-up was
      available for 313 (99.1%) of the postoperative survivors. Mean duration of follow
      up was 99.5 +/- 62.5 months. Assessment of late patency was performed in 343
      (99.4%) of 345 cases by angiography (21.2%) or duplex scanning (78.8%). A total
      of 65 (23.7%) patients died during follow-up. No deaths resulted from
      vertebrobasilar or hemispheric stroke. Cumulative Kaplan-Meier survival rate was
      89.0% +/- 3.9% at 5 years and 75.4% +/- 7.1% at 10 years. Significant
      vertebrobasilar symptom-free rate was 94.0% +/- 3.5% at 5 years and 92.8% +/-
      3.8% at 10 years. Primary patency rate was 89.3% +/- 3.6% at 5 years and 88.1% +/
      4.0% at 10 years. CONCLUSIONS: This study clearly establishes the excellent long
      term results of DVA reconstruction for the treatment of extracranial lesions of
      the vertebral artery. However, every effort should be made to reduce the rate of
      early postoperative occlusions. The subgroup of patients involving combined ICA
      and DVA reconstruction remains at high risk of postoperative stroke.

PMID- 12218981
TI  - Combined coronary artery bypass with carotid endarterectomy: do women have worse
      outcomes?
AB  - OBJECTIVE: Women undergoing coronary artery bypass grafting (CABG) have higher
      mortality and morbidity in numerous studies. Although controversial, similar
      results have been seen in women undergoing carotid endarterectomy. We examined
      the results of combined eversion CEA/CABG by one group to analyze if the outcome
      is different between men and women in this setting. METHOD: The records of all
      patients undergoing combined eversion CEA/CABG were reviewed from our vascular
      registry between January 1992 and January 2001. Indications, demographics,
      morbidity, and mortality were retrieved. These results were compared on the basis
      of gender as well as to patients undergoing CEA alone. Significance was assessed
      using Theta(2) analysis. RESULTS: There were 563 combined eversion CEA/CABG
      procedures performed over the 9-year study period: 324 in men and 239 in women.
      Asymptomatic >70% stenosis was seen in 275 (85%) male patients and 215 (90%)
      female patients (P = not significant [NS]). Stroke was found in four men vs three
      women (1.2% vs 1.3%, P = NS), whereas death occurred in 13 men and five women
      (4.0% vs 2.1%, P = NS). Thirty-day stroke/mortality was 4.9% in men vs 3.3% in
      women (P = NS). During the same period, patients undergoing CEA alone were
      subject to a stroke-mortality rate of 1.6% in men and 1.2% in women (P = NS).
      CONCLUSION: This series demonstrated no difference in outcome among patients
      undergoing combined eversion CEA/CABG procedures on the basis of gender. Although
      the results demonstrate a significantly higher mortality and morbidity in
      patients undergoing combined procedures when compared to carotid surgery alone,
      the combined procedures can be performed safely in both genders. The large number
      of asymptomatic patients in both the combined and solo procedures may have
      positively influenced these results.

PMID- 12218982
TI  - Obstructive external iliac arteriopathy in avid bicyclists: new and variable
      histopathologic features in four women.
AB  - OBJECTIVE: Avid competition bicycling may be associated with the development of
      external iliac artery stenosis. European studies have documented endofibrosis
      that primarily has affected young men. Our objective was to review the
      histopathologic features of obstructed external iliac arteries resected from avid
      competition bicyclists at a single institution. METHOD: Medical records and
      microscopic slides were reviewed from all competitive bicyclists who had
      undergone resection and graft placement for segmental external iliac artery
      disease at Mayo Clinic (Rochester, Minn) between 1991 and 2001. RESULTS: Of seven
      patients (five female, two male) seen with external iliac obstructive disease,
      four underwent resection and graft placement and thus had specimens available for
      histopathologic review. Ages of these four patients, all of whom were women,
      ranged from 31-40 years (mean, 36 years). Claudication was the primary symptom in
      all four women. There were five iliac arteries involved in the four women, and
      pre-operative arteriography showed stenotic disease in these arteries, ranging
      from subtle stenosis to occlusion. Gross examination of the five resected
      arteries showed wall thickening and luminal narrowing, without aneurysm
      formation. Microscopically, luminal thrombus was observed in two arteries (one
      old and one recent). Intimal thickening affected four specimens (symmetric in
      three and asymmetric in one). Thickening was the result of smooth muscle
      hyperplasia, with only mild collagen or elastin deposition. Medial hypertrophy
      was present in three specimens (symmetric in two and asymmetric in one), one of
      which also contained focal calcification. Adventitial thickening was prominent in
      four (symmetric in two and asymmetric in two) and was due to smooth muscle
      hyperplasia. There was no intimal, medial, or adventitial inflammation.
      CONCLUSIONS: In contrast to previous reports, iliac arteriopathy among
      competition bicyclists may occur in women. The microscopic lesions responsible
      for stenosis are more varied than the "endofibrosis" that has been previously
      documented. In addition to the intimal fibrosis and luminal thrombosis noted by
      others, we describe medial and adventitial responses to repetitive trauma.
      Accordingly, we favor the term "external iliac arteriopathy" for this disease
      entity.

PMID- 12218983
TI  - Superficial femoral artery aneurysms: an unusual entity?
AB  - OBJECTIVE: The purpose of this study was to investigate the mode of presentation
      of superficial femoral artery aneurysms, their association with other arterial
      aneurysms, and their operative treatment. METHOD: Records of patients with
      superficial femoral artery aneurysms seen at our institution from 1990 to 2000
      were reviewed retrospectively with attention to presenting symptoms, clinical
      examination, arteriographic findings, and operative management. RESULTS: Eleven
      of 13 aneurysms (85%) were in men. Nine (69%) were associated with aortic or
      iliac aneurysms, and seven (54%) with femoral or popliteal aneurysms. Six
      patients (46%) presented with distal ischemia, four (31%) presented with a thigh
      mass, and three (23%) were discovered during investigation for other vascular
      problems. No ruptured superficial femoral artery aneurysms were seen. Eleven
      patients underwent successful aneurysm resection and bypass grafting. Two
      patients underwent amputation. There were no operative mortalities. CONCLUSIONS:
      Patients with superficial femoral artery aneurysms may present with distal
      ischemia, with a pulsatile thigh mass, with rupture and bleeding, or the
      aneurysms may be discovered during other investigations. The high incidence of
      complications suggests that resection and grafting should be performed
      electively, and the frequent association of aortoiliac or peripheral aneurysms
      mandates thorough investigation and follow-up.

PMID- 12218984
TI  - Improved assessment of the hemodynamic significance of borderline iliac stenoses
      with use of hyperemic duplex scanning.
AB  - OBJECTIVE: To improve the assessment of the hemodynamic significance of
      borderline iliac stenoses (stenosis with a peak systolic velocity [PSV] ratio
      between 1.5 and 3.5) by means of hyperemic duplex scanning. The duplex ultrasound
      parameter-absolute increase in PSV across the stenosis after exercise (Delta
      PSV(e))-was studied prospectively. PATIENTS AND METHODS: Fifty-eight legs in 53
      consecutive patients with symptomatic arterial obstructive disease with
      borderline iliac stenosis were studied prospectively. Ultrasound velocity data
      collected after exercise on a bicycle ergometer at 2 W/kg during 2 minutes were
      judged against the assessment of the hemodynamic significance by means of
      intraarterial pressure measurement, before and after the administration of 50 mg
      papaverine. RESULTS: On the basis of receiver operating characteristic curves
      traced for 43 iliac stenoses in 39 patients who finished the exercise, Delta
      PSV(e) > or = 1.4 m/s had optimal sensitivity of 93% (95% confidence interval
      [CI],.77-.99), specificity of 87% (95% CI,.60-.98), positive predictive value of
      93% (95% CI,.77-.99) and negative predictive value of 87% (95% CI,.60-.98).
      CONCLUSIONS: The results of this study show that Delta PSV(e) with a cutoff value
      of 1.4 m/s in combination with the PSV ratio improves the assessment of the
      hemodynamic significance of borderline iliac artery stenoses if the patient can
      accomplish the workload.

PMID- 12218985
TI  - Southern Association for Vascular Surgery William J. von Leibig Award.
      Inflammation and intimal hyperplasia associated with experimental pulmonary
      embolism.
AB  - OBJECTIVE: We tested the hypothesis that a venous thromboembolism to the
      pulmonary arterial system (pulmonary embolism [PE]) would cause an inflammatory
      response within the pulmonary arterial (PA) wall marked by elevated cytokines and
      chemokines and an influx of inflammatory cells. METHODS: Experimental PE was
      induced in 70 rats and confirmed with angiography and O(2) saturation depression,
      and an additional 70 rats underwent sham operations. PA and lung tissue were
      removed at 3 hours and at 1, 2, 4, 6, 8, and 14 days (n = 10 per time point),
      were analyzed for proinflammatory cytokines and chemokines, and underwent
      histologic analysis. Data were analyzed with analysis of variance and the
      unpaired Student t test. RESULTS: Average gross PE resolution was 40% at 2 days,
      90% at 4 days, and 100% at 6 days. Only monocyte chemoattractant protein-1 levels
      were greater in affected PAs compared with sham PAs at 3 hours, 1 day, and 2 days
      (137 +/- 13 pg/mg protein, 285 +/- 40 pg/mg protein, and 249 +/- 36 pg/mg protein
      versus 101 +/- 6 pg/mg protein, 150 +/- 36 pg/mg protein, and 92 +/- 3 pg/mg
      protein; P <.01 for all). Keratinocyte-derived chemokine, tissue necrosis factor,
      interleukin-10, nitric oxide, P-selectin, and E-selectin levels were not
      elevated. Neutrophils infiltrated the PA wall beginning at 3 hours, peaked at 2
      days (69.4 +/- 21.7 per five high-power fields; P <.01), and returned to baseline
      by 8 days after PE. Macrophages peaked at 1 day after PE (29.3 +/- 6.9; P <.01)
      and returned to baseline by 4 days after PE. PE also was associated with a
      significantly increased intima to media ratio (P <.05), apparent at 4 days after
      PE and persisting through 14 days. CONCLUSION: PE is associated with an early
      influx of polymorphonuclears and macrophages and monocyte chemoattractant protein
      1 elevation within the PA wall. These are temporally associated with thrombus
      resolution and intimal hyperplasia. These factors may mediate these two processes
      after PE. This offers targets for further study with the hopes of minimizing the
      pathophysiologic response to PE.

PMID- 12218986
TI  - In vivo analysis of mechanical wall stress and abdominal aortic aneurysm rupture
      risk.
AB  - OBJECTIVE: The purpose of this study was to calculate abdominal aortic aneurysm
      (AAA) wall stresses in vivo for ruptured, symptomatic, and electively repaired
      AAAs with three-dimensional computer modeling techniques, computed tomographic
      scan data, and blood pressure and to compare wall stress with current clinical
      indices related to rupture risk. METHODS: CT scans were analyzed for 48 patients
      with AAAs: 18 AAAs that ruptured (n = 10) or were urgently repaired for symptoms
      (n = 8) and 30 AAAs large enough to merit elective repair within 12 weeks of the
      CT scan. Three-dimensional computer models of AAAs were reconstructed from CT
      scan data. The stress distribution on the AAA as a result of geometry and blood
      pressure was computationally determined with finite element analysis with a
      hyperelastic nonlinear model that depicted the mechanical behavior of the AAA
      wall. RESULTS: Peak wall stress (maximal stress on the AAA surface) was
      significantly different between groups (ruptured, 47.7 +/- 6 N/cm(2); emergent
      symptomatic, 47.5 +/- 4 N/cm(2); elective repair, 36.9 +/- 2 N/cm(2); P =.03),
      with no significant difference in blood pressure (P =.2) or AAA diameter (P =.1).
      Because of trends toward differences in diameter, comparison was made only with
      diameter-matched subjects. Even with identical mean diameters,
      ruptured/symptomatic AAAs had a significantly higher peak wall stress (46.8 +/-
      4.5 N/cm(2) versus 38.1 +/- 1.3 N/cm(2); P =.05). Maximal wall stress predicted
      risk of rupture better than the LaPlace equation (20.7 +/- 5.7 N/cm(2) versus
      18.8 +/- 2.9 N/cm(2); P =.2) or other proposed indices of rupture risk. The
      smallest ruptured AAA was 4.8 cm, but this aneurysm had a stress equivalent to
      the average electively repaired 6.3-cm AAA. CONCLUSION: Peak wall stresses
      calculated in vivo for AAAs near the time of rupture were significantly higher
      than peak stresses for electively repaired AAAs, even when matched for maximal
      diameter. Calculation of wall stress with computer modeling of three-dimensional
      AAA geometry appears to assess rupture risk more accurately than AAA diameter or
      other previously proposed clinical indices. Stress analysis is practical and
      feasible and may become an important clinical tool for evaluation of AAA rupture
      risk.

PMID- 12218987
TI  - Biphasic response of tropoelastin at the poststenotic dilation segment of the
      rabbit aorta.
AB  - OBJECTIVE: The purpose of this study was to assess the time course of
      tropoelastin gene expression in the poststenotic dilatation segment of rabbit
      aorta with experimental coarctation. METHODS: Midthoracic aortic coarctation was
      created in rabbits to produce a PSD. The time points of the study after
      coarctation were 1, 3, and 7 days and 2, 4, and 8 weeks (n = 3 each). Additional
      animals (n = 6) were subjected to hypercholesterolemia for analysis of
      tropoelastin expression in intimal lesions. Northern and Western blot analyses
      were used to quantitate tropoelastin messenger RNA (mRNA) and protein, and
      immunohistochemistry was used to analyze tropoelastin distribution. RESULTS:
      Thoracic aortic coarctation produced a moderate stenosis, which resulted in PSD.
      mRNA levels in the PSD segment decreased at days 1 and 3, followed by an increase
      at 2 and 4 weeks (P <.05 versus controls). This biphasic change in tropoelastin
      mRNA was associated with increase in tropoelastin protein levels at 2 and 4 weeks
      (P <.05 versus controls). PSD diameter reached a maximum at 4 weeks and did not
      increase significantly thereafter. The number of medial elastic laminae in PSD
      was reduced slightly, but media thickness was unchanged. Intimal lesions were
      much smaller in the PSD segment than in the proximal segment in animals with
      hypertension superimposed with hypercholesterolemia. Moreover, tropoelastin
      protein distributed not only in the intima but also in the media of the PSD.
      CONCLUSION: Tropoelastin gene expression is regulated in a biphasic pattern and
      precedes PSD formation. The differential distribution of tropoelastin in the
      media suggests a role for tropoelastin in the poststenotic adaptation response,
      which may provide increased elasticity to the PSD wall.

PMID- 12218988
TI  - 17 beta-estradiol attenuates intimal hyperplasia and macrophage accumulation with
      a reduction in monocyte chemoattractant protein 1 expression in a vein graft
      model.
AB  - OBJECTIVE: Autogenous vein grafts are commonly used for arterial reconstructive
      procedures. Their success is limited by the development of intimal hyperplasia, a
      fibroproliferative disease that predisposes the grafts to occlusive stenosis. Our
      goal was to assess whether 17 beta-estradiol (E(2)) inhibits vein graft intimal
      hyperplasia coincident with a reduction in monocyte chemoattractant protein 1
      (MCP-1) expression and macrophage accumulation. METHOD: Male Lewis rats were
      implanted with time-release pellets that contained 0.5 mg E(2) (E5 group) or
      placebo (PL group). Epigastric vein to common femoral artery interposition grafts
      were harvested at 2, 4, 8, and 12 weeks after surgery. We assessed
      macrophage/monocytes numbers, proliferating cell nuclear antigen, MCP-1, and
      transforming growth factor-beta1 with use of immunohistochemistry. MCP-1 message
      expression was quantified by real-time polymerase chain reaction. RESULTS: The
      time-release pellets raised the serum E(2) level to greater than 250 pg/mL on the
      day of surgery. Serum E(2) level declined to 43 +/- 13 pg/mL by 4 weeks and to
      baseline by 6 weeks. We found that the neointimal area ratio was reduced
      significantly in the E5 group at 2 and 4 weeks (45%, P <.05, and 68%, P < 0.05,
      respectively) relative to that in the PL group. The number of proliferating cells
      was reduced in the E5 group. There was a significant attenuation of MCP-1
      expression and of the number of macrophages accumulating in the graft with E(2)
      treatment. Furthermore, MCP-1 messenger ribonucleic acid expression was also
      significantly attenuated in the E5 group at 4 weeks when compared to the PL
      group. There was no significant difference between the two groups in the
      expression of transforming growth factor-beta1. CONCLUSIONS: E(2) treatment
      reduces vein-graft intimal hyperplasia coincident with a reduction in MCP-1
      expression, macrophage accumulation, and cell proliferation.

PMID- 12218989
TI  - Excision and autogenous revascularization of an infected aortic stent graft
      resulting from a urinary tract infection.

PMID- 12218990
TI  - Distal septic emboli and fatal brachiocephalic artery mycotic pseudoaneurysm as a
      complication of stenting.
AB  - The use of percutaneous angioplasty with subsequent intravascular metallic stent
      placement has gained increasing acceptance over the past decade. Infections of
      these stents appear to be uncommon; however, the rarity of this complication may
      in part be the result of a lack of availability of long-term follow-up data. A
      number of examples of infected cardiac and peripheral vascular stents have been
      reported, often with fatal consequences. Herein, we report a 74-year-old woman
      who underwent subclavian and brachiocephalic artery angioplasty and stent
      placement for symptomatic stenoses. Six months after the initial intervention,
      the patient returned with restenosis of the stents and underwent repeat
      angioplasty to restore full patency. Two weeks later, the patient was readmitted
      with generalized malaise and multiple erythematous, macular lesions on the right
      forearm and hand. Blood cultures grew Staphylococcus aureus, and a computed
      tomographic scan of the chest showed a large brachiocephalic artery
      pseudoaneurysm with surrounding hematoma. Despite prompt surgical intervention,
      this complication proved ultimately fatal. Infections of metallic endovascular
      stents are potentially life-threatening complications and must be addressed
      urgently, including possible surgical intervention.

PMID- 12218991
TI  - Subclavian vein thrombosis caused by an unusual congenital clavicular anomaly in
      an atypical anatomic position.
AB  - The optimal surgical management of subclavian vein effort thrombosis remains a
      dilemma because outcomes after different treatment strategies are only on the
      basis of small retrospective series. SVT treatment should be on the basis of the
      cause of thrombosis. Primary effort thrombosis or Paget-Schroetter syndrome
      frequently necessitates a surgical approach. The type of surgery has to be
      individualized after careful diagnostic evaluation. We report a congenital
      clavicular exostosis that had not been identified with chest radiograph and
      computed tomographic scan that caused SVT in a young woman. This unusual cause of
      Paget-Schroetter syndrome was treated with a unique approach.

PMID- 12218992
TI  - Mural thrombus of the aorta in association with homozygous plasminogen activator
      inhibitor type 1 (PAI-1)-675(4G) and heterozygous GP Ia 807C/T genotypes.
AB  - Thrombus formation in the thoracic and abdominal aorta without evidence of
      arteriosclerotic disease is very uncommon. We present a case of a 50-year-old
      woman with a mural thrombus of the upper abdominal aorta associated with a
      combination of two mutations predisposing for thrombophilia. The genetic analysis
      showed a homozygous mutation of plasminogen activator inhibitor type 1 (PAI-1)
      675 (4G) and a heterozygous mutation of GP Ia 807C/T. To our knowledge, this is
      the first report of the combination of both mutations occurring in a patient with
      isolated thrombus formation of the aorta.

PMID- 12218993
TI  - New method to create a vascular arteriovenous fistula in the arm with an
      endoscopic technique.
AB  - We describe a new technique in which the basilic vein is transposed
      subcutaneously with endoscopic surgery to create a vascular access in the arm.
      The vein was harvested with the Endoscopic Vascular Surgery System (Olympus Co,
      Tokyo, Japan). We could harvest a vessel about 25 cm long with endoscopy. After
      vessel transposition, an arteriovenous fistula was created in the usual manner.
      In all 10 patients, we created an effective blood access as scheduled before
      surgery. We could use the arteriovenous fistula 6 days after surgery and get
      blood flow in all cases.

PMID- 12218994
TI  - Is vascular surgery in danger of losing the vascular laboratory?

PMID- 12218995
TI  - The Titanic revisited: professional liability and access to care.

PMID- 12218996
TI  - Coronary revascularization prior to elective vascular surgery: does it reduce
      cardiac risk?

PMID- 12218997
TI  - Regarding "Can carotid endarterectomy improve metabolic status in patients with
      asymptomatic internal carotid artery flow lesion? Studies with localized in vivo
      proton magnetic resonance spectroscopy".

PMID- 12218998
TI  - Strategic issues for biomedical technology development.

PMID- 12218999
TI  - Consent for residents to perform surgery.

PMID- 12219000
TI  - Society of University Surgeons statement on surgical resident work hours and
      education.

PMID- 12219001
TI  - The Society of University Surgeons in the 21st century--the mission, the vision,
      and the commitment to excellence.

PMID- 12219002
TI  - Selective targeting of the nuclear factor-kappaB pathway enhances tumor necrosis
      factor-related apoptosis-inducing ligand-mediated pancreatic cancer cell death.
AB  - BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a
      member of the tumor necrosis factor family, selectively induces apoptosis in
      various cancer cells; however, certain cancers can evade TRAIL-mediated
      apoptosis. FLICE-like inhibitory protein (FLIP), an inhibitor of caspase-8, (also
      known as FLICE) is regulated by the transcription factor nuclear factor-kappaB
      (NF-kappaB) and can contribute to TRAIL resistance. The purpose of our study was
      to determine whether inhibition of NF-kappaB can enhance TRAIL-mediated
      pancreatic cancer cell death and decrease FLIP levels. METHODS: The human
      pancreatic cancer cell lines MIA PaCa-2 and L3.6 were treated with TRAIL, NEMO
      binding domain (NBD) peptide (a novel selective NF-kappaB inhibitor), or a
      combination of both. Cell viability and apoptosis were measured. Gel mobility
      shift assays were performed to assess NF-kappaB binding activity. Western blots
      were performed to assess FLIP levels after treatment with NBD or infection with
      an adenovirus encoding mutated IkappaBalpha. RESULTS: The aggressive L3.6 cell
      line was resistant to TRAIL treatment, whereas MIA PaCa-2 cells were sensitive to
      TRAIL. The combination of TRAIL and NBD significantly decreased cell viability
      and increased apoptosis in L3.6 cells. Cellular levels of FLIP were decreased by
      inhibition of NF-kappaB (either by NBD treatment or mutant IkappaBalpha
      infection). CONCLUSIONS: Our findings demonstrate resistance of the aggressive
      L3.6 pancreatic cell line to TRAIL treatment alone; inhibition of NF-kappaB by
      NBD increased TRAIL-mediated cell death and decreased FLIP protein levels. Novel
      agents that selectively target the NF-kappaB pathway may be useful adjuvant
      therapies for chemoresistant pancreatic cancers.

PMID- 12219003
TI  - Prospective, randomized evaluation of a cuffed expanded polytetrafluoroethylene
      graft for hemodialysis vascular access.
AB  - BACKGROUND: A cuffed expanded polytetrafluoroethylene (ePTFE) hemodialysis graft
      was developed to address the problem of recurrent stenosis at the graft-vein
      anastomosis. The purpose of this study was to compare graft patency and blood
      flow rates of cuffed and noncuffed (standard) ePTFE grafts placed for
      hemodialysis access. METHODS: Forty-eight patients were prospectively randomized
      and followed for up to 24 months after placement of a cuffed or standard ePTFE
      graft for hemodialysis access. Study end points included time to graft failure
      and blood flow rates on hemodialysis. RESULTS: Risk factors for graft failure
      were similar in both groups. However, the overall incidence of graft failure was
      significantly lower in the cuffed ePTFE graft group (P =.039). Graft patency
      rates in the cuffed versus standard groups were 64% versus 32% at 12 months (P
      =.037) and 58% versus 21% at 24 months (P =.0213). No cuffed ePTFE graft failed
      as a result of venous outflow stenosis. Average graft flow rates were similar
      when first measured 3 months postoperatively (845 mL/min, cuffed vs 715 mL/min,
      standard; P =.51) but declined more rapidly in the standard group (12 months, 623
      vs 253 mL/min [P =.037]; 24 months, 531 vs 121 mL/min [P =.012]). CONCLUSIONS:
      The cuffed ePTFE graft was associated with increased blood flow rates during
      hemodialysis and improved graft patency compared with a standard ePTFE graft. Our
      results suggest a beneficial effect of the cuffed venous geometry for
      hemodialysis vascular access.

PMID- 12219004
TI  - Restoration of E-cadherin/beta-catenin expression in pancreatic cancer cells
      inhibits growth by induction of apoptosis.
AB  - BACKGROUND: beta-Catenin is a component of the E-cadherin/catenin adhesion
      complex that maintains epithelial cell integrity. We have previously observed
      decreased beta-catenin expression in both human pancreatic cancer cell lines and
      primary tumors. To determine the significance of this finding with respect to
      pancreatic carcinogenesis, this study evaluated the effects of restoring
      expression of beta-catenin with and without E-cadherin in pancreatic cancer
      cells. METHODS: MiaPaca-2 cells were stably transfected with full-length cDNAs
      for beta-catenin, E-cadherin, or a mutated E-cadherin lacking the beta-catenin
      binding domain. Doubly transfected cell clones containing beta-catenin and either
      E-cadherin or deleted E-cadherin were also selected. Assays for cell adhesion,
      cell cycle profile, motility, and apoptosis were performed. RESULTS: Cell clones
      expressing beta-catenin alone or beta-catenin and deleted E-cadherin did not
      differ significantly from the parental cell lines in any of the assays performed.
      In contrast, MiaPaca-2 cell clones expressing both beta-catenin and E-cadherin
      showed tight adhesion, decreased cell growth, and a significantly increased
      apoptotic index as compared to the parental line or singly transfected clones.
      CONCLUSIONS: MiaPaca-2 cells undergo apoptosis at a significantly increased rate
      after restoration of the E-cadherin/beta-catenin adhesion complex. This increase
      in apoptosis is dependent on the ability of E-cadherin to bind beta-catenin. Loss
      of beta-catenin expression may therefore provide pancreatic cancer cells with a
      growth advantage that contributes to tumor progression.

PMID- 12219005
TI  - Targeted gene therapy with CD40Ig to induce long-term acceptance of liver
      allografts.
AB  - BACKGROUND: The purpose of this study was to modulate the immune response of rat
      liver transplant recipients by adenovirus-mediated gene transfer of CD40Ig, a
      secretable fusion protein designed to block the CD40-CD154 T-cell costimulation
      pathway. METHODS: CD40Ig complementary DNA was created by joining the reverse
      transcriptase-polymerase chain reaction complementary DNA products for the
      extracellular domain of murine CD40 to the Fc portion of murine IgG2a. AdCD40Ig
      and AdSIg (IgG2a-Fc control) recombinant adenoviruses were used to transduce
      donor liver grafts before nonarterialized orthotopic rat liver transplantation.
      Donor specific unresponsiveness was examined with skin transplants. RESULTS: All
      rats (n = 6) that received liver allografts transduced with AdCD40Ig survived
      >100 days with normal liver histology. Serum levels of CD40Ig at 10, 30, 60, and
      100 days after transplantation ranged from 100 to 500, 100 to 250, 5 to 40, and 2
      to 10 microg/mL, respectively. Mean survival of rats (n = 4) that received liver
      allografts transduced with AdSIg control adenovirus was 9.25 +/- 2.9 days. Long
      term survivors were rechallenged with skin grafts 100 days after liver
      transplantations. Survival was 72, >100 (x4) days for donor specific allogeneic
      skin grafts and 14, 14, 18, 19, and 21 days for third-party allogeneic skin
      grafts. CONCLUSIONS: Adenovirus-mediated gene transfer of CD40Ig into cold
      preserved liver allografts before transplantation results in high levels of
      transgene expression with resultant long-term survival of hepatic allografts and
      donor specific unresponsiveness.

PMID- 12219006
TI  - Platelet-activating factor priming of inflammatory cell activity requires
      cellular adherence.
AB  - BACKGROUND: Platelet-activating factor (PAF) primes tissue-fixed inflammatory
      cells, but has no effect on circulating cells. Adherence of inflammatory cells
      leads to cytoskeletal reorganization, which is essential for optimal inflammatory
      function. The purpose of this study was to investigate whether cellular adherence
      plays a role in PAF priming of inflammatory cells. METHODS: Differentiated THP-1
      cells were maintained under adherent and nonadherent conditions. Selected cells
      were pretreated with PAF, followed by endotoxin stimulation. Cellular and nuclear
      proteins were analyzed by Western blot for components of the Toll-like receptor
      mediated signaling cascade. Cytokine analysis was performed by enzyme-linked
      immunosorbent assay. RESULTS: Endotoxin led to activation of interleukin (IL)-1
      associated kinase, extracellular signal-regulated kinase 1/2 and p38, and nuclear
      translocation of nuclear factor-kappaB, all of which were significantly enhanced
      by previous cellular adherence. PAF led to priming only under adherent
      conditions, demonstrated by increased IL-1-associated kinase and extracellular
      signal-regulated kinase 1/2 activity; nuclear factor-kappaB translocation; and IL
      6, IL-8, and tumor necrosis factor-alpha production over non-PAF-treated cells.
      PAF had no significant effect on p38 activity or IL-10 production under any
      condition. CONCLUSIONS: PAF primes mononuclear cells by increasing Toll-mediated
      signaling only under adherent conditions. This, therefore, would limit PAF
      induced priming in vivo to foci of stimulated adherent inflammatory cells with
      little effect systemically on circulating cells.

PMID- 12219007
TI  - Transfer of "infectious" cardiac allograft tolerance induced by donor-specific
      transfusion.
AB  - BACKGROUND: "Infectious tolerance" has been defined as the tolerance induced in a
      new recipient by the adoptive transfer of cells from a recipient accepting an
      allograft after anti-CD4 and anti-CD8 monoclonal antibody treatment. A clear
      understanding of the mechanisms responsible for graft acceptance after donor
      specific blood transfusion (DST) has remained elusive. We examined the
      development and "infectious" nature of immunologic changes resulting in
      indefinite survival of LEW to DA rat cardiac allografts after DST alone without
      the need for antibody. METHODS: One hundred x 10(6) LEW splenocytes (SC) as DST
      were injected intravenously into DA recipients 7 days before LEW cardiac
      transplantation. Subsequently, 100 x 10(6) SC harvested from a DA recipient 30,
      60, or 100 days after graft acceptance were adoptively transferred into lightly
      gamma-irradiated (450 rad) naive DA recipients 24 hours before a second LEW
      cardiac allograft. Subsequent graft function was determined. RESULTS: Adoptive
      transfer of SC from the DST-treated DA rats 30 days after LEW heart transplant
      acceptance into naive gamma-irradiated DA rats failed to transfer tolerance to
      LEW cardiac allografts. However, SC from DA rats bearing LEW hearts for more than
      60 days induced indefinite tolerance to all LEW hearts. This infectious tolerance
      could be adoptively transferred again to a second DA recipient. CONCLUSIONS: DST
      generated regulatory cells can downregulate naive lymphocytes to promote
      allograft acceptance. This tolerance can be expanded and serially transferred to
      a subsequent naive cardiac recipient.

PMID- 12219008
TI  - Transforming growth factor-beta1 induces apoptosis in vascular endothelial cells
      by activation of mitogen-activated protein kinase.
AB  - BACKGROUND: Vascular endothelial cell apoptosis is central in atherosclerosis and
      intimal hyperplasia. Transforming growth factor (TGF)-beta1 induces endothelial
      cell apoptosis through unidentified mechanism(s). Although TGF-beta1 signals
      through the Smad proteins, in some nonendothelial cell types it also activates
      the mitogen-activated protein kinase (MAPK) (extracellular signal-regulated
      kinase, c-Jun N-terminal kinase, and p38 MAPK [p38(MAPK)]). p38(MAPK) relays
      apoptotic signals in several cell types. We hypothesized that TGF-beta1 activates
      endothelial cell MAPKs and induces apoptosis through p38(MAPK) activation.
      METHODS: Human umbilical vein or bovine capillary endothelial cells were
      incubated with TGF-beta1 for 0.5 to 12 hours. MAPK activation was characterized
      by Western blotting with antibodies to phosphorylated extracellular signal
      regulated kinase 1/2, p38(MAPK), or c-Jun N-terminal kinases 1/2. To study
      apoptosis, extracts of cells incubated with TGF-beta1 for 6 hours with or without
      MAPK inhibitors were characterized by Western blotting analysis of poly (ADP
      Ribose) polymerase degradation. RESULTS: TGF-beta1 induced p38(MAPK),
      extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase 1/2
      activation and increased apoptosis. Inhibition of p38(MAPK) significantly reduced
      TGF-beta1-induced apoptosis. In contrast, inhibition of other signaling pathways
      was ineffective. CONCLUSIONS: TGF-beta1 induces endothelial cell apoptosis
      through p38(MAPK) activation. Because TGF-beta1 is upregulated in vascular
      remodeling, p38(MAPK) is a potential target to prevent endothelial cell apoptosis
      during this process.

PMID- 12219009
TI  - Tyrosine phosphorylation of vascular endothelial cadherin and the regulation of
      microvascular permeability.
AB  - BACKGROUND: Adherens junctions (AJ), by their association with the endothelial
      cytoskeleton, maintain microvascular barrier integrity. Phosphorylation states of
      AJ proteins, such as vascular endothelial (VE) cadherin, can potentially alter
      the interactions between component AJ proteins. Furthermore, AJ protein
      phosphorylation is susceptible to regulation by inflammatory mediators. We
      previously demonstrated the importance of VE cadherin in tumor necrosis factor
      (TNF)-mediated endothelial permeability. We now postulate that TNF-induced
      endothelial permeability is associated with tyrosine phosphorylation of VE
      cadherin. METHODS: Confluent monolayers of human umbilical vein endothelial cells
      were exposed to saline solution, TNF-alpha (100 U/mL) or TNF and the Src-tyrosine
      kinase inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4
      d]pyrimidine. Permeability was assessed by fluorescein isothiocyanate-dextran
      flux. VE-cadherin phosphorylation was determined by immunoprecipitation and
      immunoblotting with antiphosphotyrosine antibody. Data are expressed as mean +/-
      SEM and analyzed by analysis of variance. RESULTS: TNF-alpha-induced tyrosine
      phosphorylation of VE cadherin and increased intercellular gap formation. These
      changes were associated with increased endothelial-cell monolayer permeability,
      all of which were prevented by 4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4
      d]pyrimidine. Exposure to an inactive tyrphostin, AG9 (negative control), did not
      prevent TNF-induced endothelial permeability. CONCLUSIONS: We conclude that
      tyrosine phosphorylation of VE cadherin is an important regulatory pathway
      associated with TNF-induced endothelial barrier dysfunction. Modulating AJ
      protein phosphorylation may provide targets for therapy during inflammation.

PMID- 12219010
TI  - Plasma from patients undergoing major open surgery stimulates in vitro tumor
      growth: Lower insulin-like growth factor binding protein 3 levels may, in part,
      account for this change.
AB  - BACKGROUND: Plasma from laparotomized mice has been shown to stimulate in vitro
      tumor growth when compared to results with preoperative plasma. This study
      assessed the effect of plasma from patients who underwent major open (OS) or
      laparoscopic surgery (LS) on in vitro tumor cell growth. METHODS: Eighty-four
      patients undergoing major abdominal surgery were studied (45 OS, 39 LS).
      Peripheral blood was collected preoperatively (PreOP) and on days 1 (POD1) and 3
      (POD3) after operation. HT29 human colon cancer cells were plated with samples of
      the plasma. Proliferation was assessed by cell counts and the bromodeoxyuridine
      incorporation assay. Insulin-like growth factor binding protein 3 was detected in
      plasma by Western blot analysis. RESULTS: Increased mitogenic activity was noted
      in POD1 OS plasma when compared to PreOP OS plasma results (P <.005). This
      increase correlated with the length of incision (r = 0.58, P <.01). No
      differences were noted when the PreOP LS and POD1 LS results were compared or for
      any of the POD3 versus PreOP comparisons. CONCLUSIONS: Major OS is associated
      with alterations in plasma composition that promote HT29 tumor cell proliferation
      in vitro. As shown, this effect was due, at least in part, to surgery-related
      depletion of insulin-like growth factor binding protein 3 in peripheral blood.

PMID- 12219011
TI  - Recombinant human neutral endopeptidase ameliorates pancreatic elastase-induced
      lung injury.
AB  - BACKGROUND: Genetic deletion of neutral endopeptidase (NEP), a cell-surface
      metalloprotease that degrades proinflammatory peptides, exacerbates lung injury
      induced by pancreatic elastase in a model of pancreatitis-associated lung injury.
      We tested 3 hypotheses: (1) genetic deletion of NEP prolongs lung recovery after
      elastase injections; (2) elastase-mediated lung injury is associated with down
      regulation of NEP; and (3) pretreatment of NEP (-/-) and (+/+) animals with
      recombinant human NEP (rhNEP) reduces pulmonary damage in this model. METHODS:
      NEP (+/+) or (-/-) mice were injected with pancreatic elastase (0.085 U/g/dose
      intraperitoneally) or saline carrier at t = 0 hours and t = 1 hour. Some mice
      were pretreated with rhNEP (3 mg/kg intraperitoneally). Serum elastase, lung
      histologic score, myeloperoxidase, and NEP activities were measured at 4, 8, or
      12 hours. RESULTS: NEP (-/-) mice had worse pulmonary inflammation at 4 and 8
      hours versus (+/+) mice. Lung NEP activity was similar in elastase-treated and
      control (+/+) animals. Pretreatment with rhNEP reduced myeloperoxidase and
      improved histology at 4 hours in NEP (-/-) and (+/+) mice. CONCLUSIONS:
      Pancreatic elastase induces lung injury that is worse and prolonged in NEP (-/-)
      mice. Pretreatment with rhNEP ameliorates this injury. Thus, upregulation of NEP
      is a potential therapeutic approach for pancreatitis-associated lung injury.

PMID- 12219012
TI  - Tissue-engineered colon exhibits function in vivo.
AB  - BACKGROUND: Postcolectomy morbidities include important changes in enterohepatic
      circulation, stool microbiology, and absorption. The surgical substitution of an
      ileal pouch for the absent colon also has a number of serious complications. We
      report in vivo colon replacement by tissue-engineered colon (TEC) in lieu of an
      ileal pouch. METHODS: End-ileostomies were created in 22 male Lewis rats. In 11
      animals, side-to-side ileum-TEC anastomosis was performed 1 cm from the stoma.
      This group was compared with end-ileostomy alone. Serial weights were measured,
      and animals were harvested sequentially for assessment of histologic signs of
      pouchitis. Transit times, stool dry and wet weights, and serum and stool colon
      function markers were collected. RESULTS: Animals survived 41 days. Weight loss
      was more than 1.5 times greater in the end-ileostomy alone group compared with
      the ileum-TEC group. Transit times were significantly longer in the ileum-TEC
      group than the end-ileostomy alone group, with lower stool moisture content and
      higher total serum bile acids. Animals without TEC had statistically significant
      hyponatremia, elevated serum urea nitrogen, and lower stool short chain fatty
      acids (13.5 micromol/kg vs 84.2) with an abnormal distribution. CONCLUSIONS: TEC
      successfully recapitulates some major physiologic functions of native large
      intestine in vivo.

PMID- 12219013
TI  - Natural killer cells contribute to the lethality of a murine model of Escherichia
      coli infection.
AB  - BACKGROUND: Cooperative interactions between natural killer (NK) cells and
      macrophages occur normally during the course of the early immune response to
      bacterial, protozoal, and viral pathogens, with each cellular compartment
      providing the other with critical stimulatory factors. We conducted the present
      study to determine whether NK cells contribute to the dysregulated immune
      response that accompanies septic shock. METHODS: An analysis of the lethality of
      Escherichia coli CP9 was conducted in mice that had been depleted of NK cells via
      the injection of an anti-asialo GM1 antibody and in CD epsilon transgenic mice
      that are deficient in both NK cells and T cells. The 2 groups of mice were
      analyzed for serum levels of interferon-gamma, tumor necrosis factor-alpha, and
      interleukin-1beta as well as activation of NFkappaB and STAT1, 2 proinflammatory
      transcription factors. RESULTS: NK cell-depleted and NK cell-deficient mice
      exhibited 80% survival in the face of an intraperitoneal bacterial challenge,
      whereas control mice all died within 12 hours. Serum levels of proinflammatory
      cytokines were markedly reduced in NK-depleted mice. NF kappaB and STAT1
      activation were also reduced. NK-depleted mice exhibited less inflammation within
      multiple organs on histologic analysis. CONCLUSIONS: These results show that NK
      cells may contribute to the lethality of bacterial infections via effects on
      cytokine production.

PMID- 12219014
TI  - Epidemiology of radical prostatectomy for localized prostate cancer in the era of
      prostate-specific antigen: an overview of the Department of Defense Center for
      Prostate Disease Research national database.
AB  - BACKGROUND: Because of public awareness and screening, the incidence of
      clinically localized prostate cancer has increased dramatically in the last 15
      years. The Department of Defense Center for Prostate Disease Research (CPDR) was
      established by the US Congress in 1991 to study prostate cancer in the US
      military health care system. A key component of CPDR is a multicenter prospective
      and retrospective prostate research database that collects comprehensive
      standardized data on all consenting patients. To verify and document changes in
      the epidemiology of men electing radical prostatectomy (RP) as primary treatment
      for their localized prostate cancer, we undertook an analysis of such cases when
      the PSA screening test became widely available and used. METHODS: The CPDR
      database consists of standardized data collection forms for each episode of care
      completed prospectively, and in some cases, retrospectively, on men with prostate
      cancer and those undergoing a prostate biopsy for presumed cancer at
      participating medical centers. In July 2001, a query of all RPs performed between
      January 1, 1991, and December 31, 2000, was conducted, revealing 3681 cases for
      analysis from 9 hospital sites. These cases were analyzed over time (calendar
      year), and changes in the characteristics of the patients, disease severity, and
      surgical results were compared. RESULTS: There was a significant shift to younger
      men undergoing RP with the median age declining to 62.3 years old by 2000, and
      more than 40% of the men were less than 60 years old. There was an increase in
      African-Americans undergoing RP and a large increase in clinical stage T1 disease
      candidates of both races representing 56.5% of men by 2000. There was a large
      increase in patients having pretreatment PSA levels between 4 and 10 ng/mL (59.2%
      by 2000). Retropubic approach was predominant (over 80%) and was associated with
      a much lower blood loss by 2000 (approximately 800 mL). There was an increase in
      use of nerve-sparing procedures, and operative time declined significantly to a
      median of 3.5 hours by 2000. Finally, there was a marked surgical stage migration
      with a higher proportion of men with organ-confined disease and negative surgical
      margins; by 2000, 63.4% had pT2 disease. The early outcomes improved with a 1
      year disease-free survival in excess of 93%. CONCLUSIONS: RP is being performed
      more commonly on younger men with earlier stage disease in the PSA era. The
      operation is now performed more rapidly with less blood loss, and the surgical
      pathology outcome end points and early disease-free survival are improved. These
      results portend well for improved long-term outcomes of surgical therapy.

PMID- 12219015
TI  - Fibroblasts promote breast cancer cell invasion by upregulating tumor matrix
      metalloproteinase-9 production.
AB  - BACKGROUND: Thrombospondin-1 (TSP-1) promotes breast cancer cell invasion of
      collagen by upregulating matrix metalloproteinase-9 (MMP-9) production. Stromal
      TSP-1 may play a role in regulating tumor cell invasion. We hypothesize that
      fibroblasts promote breast cancer cell invasion by upregulating the production of
      MMP-9 through TSP-1. METHODS: MDA-MB-231 human breast carcinoma cells were grown
      alone or in coculture with human fibroblasts. Gelatin zymography and Western
      immunoblot analysis for MMP-9 were performed on the coculture cell media and the
      single cell media. Inhibition of fibroblast-mediated breast tumor cell invasion
      by an anti-TSP-1 or an anti-MMP-9 antibody was evaluated using a modified Boyden
      chamber. RESULTS: Coculture experiments showed an increased production of MMP-9
      when compared with breast cancer single cell culture or fibroblast single cell
      culture experiments as demonstrated by zymography and Western immunoblot
      analysis. Fibroblast-stimulated MMP-9 production was comparable with TSP-1
      stimulated MMP-9 production. Anti-TSP-1 antibody and anti-MMP-9 antibody
      inhibited fibroblast-stimulated tumor cell invasion to 30% and 26% of controls,
      respectively (P <.05). CONCLUSIONS: Fibroblasts may regulate breast cancer cell
      invasion by promoting tumor MMP-9 production through TSP-1. Inhibition of stromal
      TSP-1 stimulation of MMP-9 synthesis may prevent matrix degradation necessary for
      tumor invasion and metastasis.

PMID- 12219016
TI  - Interleukin-10 activates the transcription factor C/EBP and the interleukin-6
      gene promoter in human intestinal epithelial cells.
AB  - BACKGROUND: Interleukin (IL)-6 is produced by enterocytes in response to sepsis
      and after treatment with IL-1beta. The IL-6 promoter contains binding sites for
      multiple transcription factors, including nuclear factor-kappaB and C/EBP. The
      anti-inflammatory cytokine IL-10 downregulates nuclear factor-kappaB activity,
      but its effects on C/EBP activation and IL-6 production in the enterocyte are not
      known. METHODS: Caco-2 cells were treated with IL-1beta, IL-10, or a combination
      of the cytokines. C/EBP DNA binding activity was determined by electrophoretic
      mobility shift assay and IL-6 levels by enzyme-linked immunosorbent assay. IL-6
      promoter activation was assessed by luciferase assay. RESULTS: IL-10 treatment of
      cultured Caco-2 cells resulted in increased C/EBP DNA binding activity.
      Supershift analysis revealed upregulated DNA binding activity of C/EBP-beta but
      not C/EBP-delta. To examine if the increased DNA binding reflected gene
      activation, cells were transfected with a wild-type IL-6 promoter luciferase
      construct or with a mutated C/EBP binding site. IL-10 potentiated IL-1 beta
      induced IL-6 promoter activity. Replacing the wild-type promoter with the
      promoter containing a mutated C/EBP DNA binding sequence blocked the effect of IL
      10. When cells were treated with 0.5 ng/mL of IL-1 beta for 24 hours, IL-6
      production increased, and this response to IL-1 beta was potentiated several-fold
      by IL-10. CONCLUSIONS: IL-10 may activate the IL-6 gene in stimulated enterocytes
      by upregulating the expression and activity of C/EBP.

PMID- 12219017
TI  - Importance of Sp1 consensus motifs in the MYCN promoter.
AB  - BACKGROUND: MYCN (N-myc) amplification in neuroblastoma is associated with poor
      clinical outcome. Factors that regulate MYCN expression have not been elucidated.
      MYCN is considered a TATA-less promoter, whereas significant promoter activity
      resides within 160 bp 5' of the major transcription start site. This region
      contains two GC-rich motifs and a CT box, regions for potential transcription
      factor interaction. METHODS: To characterize DNA-protein interactions in this
      region of the MYCN promoter, electrophoretic mobility shift assays, and promoter
      reporter were used. RESULTS: A MYCN promoter fragment was incubated with HeLa
      nuclear extract, with or without competitors. Three major protein/DNA complexes
      were formed. Formation of 2 complexes could be inhibited by unlabeled Sp1
      consensus duplex and by the Sp1 site-specific drug WP631. Purified Sp1 protein
      produced a complex similar to that formed with HeLa extract. To determine whether
      these DNA/protein interactions could be blocked in a sequence-specific fashion, a
      triplex forming oligonucleotide (TFO) was used. This TFO was designed to bind in
      the major groove of the promoter, covering the CT-box (putative Sp1 binding)
      motif. When triplex formation was followed by addition of nuclear extract,
      protein binding was indeed inhibited. Functional significance of this inhibition
      was tested with pE/Bnmyc-luc, a promoter-reporter plasmid containing the human
      MYCN promoter driving luciferase expression. Incubation with TFO, but not control
      oligodeoxynucleotides, completely inhibited luciferase activity. CONCLUSIONS:
      These data suggest that protein binding does occur in regions of the MYCN
      promoter containing GC and CT box elements and that this interaction is important
      for MYCN promoter activity. By inference, these data also suggest that the
      proteins that bind in this region are Sp1 family members.

PMID- 12219018
TI  - Does increasing age have a negative impact on six-month functional outcome after
      coronary artery bypass?
AB  - BACKGROUND: Advances in medical care and improvements in catheter-based
      interventions for coronary artery disease have advanced the age at which patients
      present for coronary artery bypass graft (CABG) operations. The impact of age on
      functional outcome after CABG is unclear. METHODS: Functional outcome was
      assessed at baseline and at 6 months using the Duke Activity Status Index (DASI)
      in 337 consecutive patients undergoing primary or redo CABG. Complete functional
      outcome data were available in 292 patients (86%). RESULTS: The mean baseline
      DASI score was significantly lower in patients > or = 70 years of age (24.8 +/-
      14.5 vs 30.9 +/- 17.8, P =.002) and at 6 months (29.6 +/- 16.5 vs 38.0 +/- 17.1,
      P =.0001); however, the 6-month change in DASI score (7.2 +/- 17.5 in patients <
      70 years of age vs 4.9 +/- 14.0 in patients > or = 70 years of age, P =.23) was
      comparable. When examined in terciles of age, the 6-month change in DASI score
      was not significantly different (P =.11) in patients aged 31 to 60 years (5.8 +/-
      18.0), aged 61 to 71 years (8.7 +/- 15.7), or aged 72 to 91 years (4.0 +/- 14.6).
      CONCLUSIONS: These functional outcome results demonstrate that older patients
      present for CABG at a significantly lower functional level and remain at a
      significantly lower functional level 6 months after CABG. However, the functional
      improvement after CABG is not significantly different across age groups.

PMID- 12219019
TI  - Preexposure of murine macrophages to CpG-containing oligonucleotides results in
      nuclear factor kappaB p50 homodimer-associated hyporesponsiveness.
AB  - BACKGROUND: DNA containing the CpG motif is associated with immunomodulation of
      the innate immune response. Preexposure of macrophages to CpG DNA elicits a
      hyporesponsiveness to subsequent lipopolysaccharide (LPS) stimulation. We tested
      the hypothesis that this effect is due to decreased nuclear translocation of
      nuclear factor kappaB (NF-kappaB). METHODS: Murine macrophage-like RAW 264.7
      cells were incubated with 1.5 microg/mL CpG-containing oligonucleotides (CpG ODN)
      for 0.5 to 9 hours followed by restimulation with 1 microg/mL LPS for 20 minutes.
      Some cells were cotransfected with an NF-kappaB sensitive luciferase reporter
      construct and a control beta-gal plasmid. Cytoplasmic and nuclear extracts were
      assayed for NF-kappaB by electrophoretic mobility shift assay and supershift
      assays, for NF-kappaB, IkappaB and phospho-IkappaB by Western blot, for
      luciferase activity, and for p38, c-Jun NH(2)-terminal kinase, and extracellular
      signal-related kinase activity assay. RESULTS: NF-kappaB functional activity was
      decreased as demonstrated by luciferase activity assay in the prolonged CpG ODN
      pretreatment groups. Unlike endotoxin tolerance, CpG ODN preexposure increased
      cytoplasmic phospho-IkappaB-alpha and did not abrogate mitogen-activated protein
      kinase activity. CONCLUSIONS: In macrophages, exposure to CpG DNA increases
      expression of the inhibitory p50 NF-kappaB homodimer and decreases NF-kappaB
      activity without inhibition of IkappaB kinases. Mitogen-activated protein kinase
      activity remains intact. Understanding these interactions between different toll
      receptor ligands may provide insight into novel therapeutic modalities.

PMID- 12219020
TI  - Acidosis plus melphalan induces nitric oxide-mediated tumor regression in an
      isolated limb perfusion human melanoma xenograft model.
AB  - BACKGROUND: Isolated limb perfusion (ILP) with melphalan is an accepted treatment
      for intransit melanoma of the extremities. Using an ILP human melanoma xenograft
      model, we tested the hypothesis that acidosis augments the antitumor effect of
      melphalan and that nitric oxide (NO) induction mediates tumor regression.
      METHODS: NIH1286 human melanoma tumor bearing athymic nude rats underwent a 10
      minute ILP. Group C was perfused at physiologic pH without acid or melphalan,
      group M received melphalan at physiologic pH (7.2), group A received 0.2 N of HCl
      at pH 6.8, and group A/M received melphalan and HCl at pH 6.8. Groups 1400W + A
      and 1400W + A/M were injected with 1400W, a specific inhibitor of inducible NO
      synthase, 1 hour pre-ILP. Tumor response was followed for up to 60 days in all
      survival experiments. In 4 to 6 animals from groups C, M, A, and A/M, tumor NO
      was measured pre- and post-ILP, and tumor and thigh muscle from 2 additional
      animals in each group were collected at 20 minutes and 24 hours post-ILP and
      processed for terminal deoxynucleotidyl transferase dUTP nick end labeling
      staining. RESULTS: Maximum mean reduction in tumor size after ILP in the
      different groups was as follows: C = 0%, M = 55%, A = 99.6% (3 of 4 complete
      responses), A/M = 100% (all complete responses), 1400W + A = 0%, and 1400W + A/M
      = 25%. Median tumor NO was 0.87 +/- 0.74 (SD) micromol/L before ILP and increased
      significantly (Mann-Whitney rank sum test, P <.001) after ILP (C = +6.9%, n = 4;
      M = +7.5%, n = 5; A = +66.0%, n = 6; A/M = +35.9%, n = 6). Also, minimal
      apoptotic cell death was seen in C and M, whereas A and A/M showed evidence of
      widespread apoptosis. CONCLUSIONS: Acidosis enhances the antitumor effect of
      melphalan. NO induction appears to play a role in tumor regression.

PMID- 12219021
TI  - Angiogenic effect of fibroblast growth factor-1 and vascular endothelial growth
      factor and their synergism in a novel in vitro quantitative fibrin-based 3
      dimensional angiogenesis system.
AB  - BACKGROUND: We have developed an in vitro 3-dimensional angiogenesis system in
      which the length, distribution, and ultrastructure of induced capillary sprouts
      were analyzed in response to concentration ranges of fibroblast growth factor
      (FGF)-1 and vascular endothelial growth factor (VEGF) and synergistic activity
      quantitated. METHODS: Bovine aorta endothelial cell aggregates were embedded in
      fibrin gel (FG) supported by a nylon mesh ring. The formed disks were cultured in
      24-well plates in assay media. The test growth factors FGF-1, VEGF, or both (0 to
      100 ng/mL) with 100 KIU/mL aprotinin were added to the media. The disks (n =
      8/group) were digitally photographed and capillary sprouts quantitated. Assay
      disks were then fixed and sectioned for morphology. RESULTS: In aprotinin
      stabilized FG, aggregated ECs invaded FG radially, forming sprouts and capillary
      networks. Neovessel lumens surrounded by ECs were confirmed on hematoxylin and
      eosin and transmission electron microscopy and by formation of cell junctions by
      transmission electron microscopy. The angiogenic effects of FGF-1 and VEGF were
      dose-dependent in the range from 1 to 100 ng/mL. Significant activity of FGF-1
      started at 1 ng/mL and of VEGF at 2 ng/mL. The greatest effect was at the highest
      concentration (100 ng/mL) for both cytokines. The combination of 10 ng/mL of each
      FGF-1 and VEGF induced a significantly greater effect than the additive effects
      of FGF-1 (10 ng/mL) or VEGF (10 ng/mL) alone when analyzed with SAS system for
      mixed model (P <.0001), and that also exceeded the effects by 20 ng/mL of either
      FGF-1 or VEGF. CONCLUSIONS: A 3-dimensional capillary network can be induced in
      aprotinin-stabilized FG using FGF-1 or VEGF with synergism between the 2
      angiogens.

PMID- 12219022
TI  - Are high-volume surgeons and hospitals the most important predictors of in
      hospital outcome for colon cancer resection?
AB  - BACKGROUND: Although recent studies have reported that high-volume surgeons and
      hospitals have better outcomes for colon cancer resections, it remains unclear
      whether there are other factors that are more important than volume. This study
      aims to evaluate the importance of the volume variables relative to other factors
      in an attempt to target specific areas for improving outcomes. METHODS: Using
      nationwide data from the Healthcare Cost and Utilization Program, full-model
      logistic regression was performed on all patients undergoing colon cancer
      resection. In hospital mortality was regressed against more than 30 different
      independent variables, including demographic factors (eg, age, gender, race,
      ethnicity, and socioeconomic status), burden of morbid and comorbid disease
      (prevalence and severity), and provider variables (eg, hospital size, location,
      teaching status, hospital and surgeon volume). A separate baseline probability
      analysis was then performed to compare the relative importance for all predictor
      variables. RESULTS: The sample size for this analysis was 22,408; 622 in-hospital
      deaths occurred (2.8%). Average age was 70 years old, 51% of particIpants were
      male, and 60% had at least 1 comorbid disease. An operation was elective (64%),
      urgent (19%), or emergency (15%). The significant predictors for mortality (at P
      <.05) included age, gender, comorbid disease (ie, cardiovascular, pulmonary,
      liver), operation severity (ie, emergency, urgent), and volume (both hospital and
      surgeon). The baseline probability analysis shows that the mortality for a
      baseline case is 12/1000. If this baseline case goes to a high-volume hospital or
      surgeon, the mortality will decrease to 11/1000 and 10/1000, respectively. If a
      patient with a baseline case of colon cancer also has coexistent liver disease or
      requires an emergency operation, mortality increases to 44/1000 and 45/1000,
      respectively. Overall, the volume variables, although statistically significant,
      have a relatively smaller effect on outcome compared with other factors.
      CONCLUSIONS: Whereas other factors have a stronger association with outcome than
      volume, volume is the only acutely mutable variable. Although the regionalization
      controversy (ie, using only high-volume surgeons or hospitals) is not solved with
      our findings, this study elucidates and compares the relative importance of
      several different factors on outcome, which is essential when considering the
      conclusions and implications of this type of policy-relevant outcomes research.

PMID- 12219023
TI  - Virtual reality: immersive hepatic surgery educational environment.
AB  - BACKGROUND: Understanding the spatial relationships among the liver segments, and
      intrahepatic portal and hepatic veins is essential for surgical treatment of
      liver diseases. Teleimmersive virtual reality enables improved visualization over
      conventional media because it supports stereo vision, viewer-centered
      perspective, large angles of view, and interactivity with remote locations. We
      report a successful pilot study teaching hepatic surgical principles using
      teleimmersion. METHODS: We developed a teleimmersive environment for teaching
      with biomedical models including virtual models of the liver segments and portal
      and hepatic veins. Using the environment, 1 instructor gave a workshop to 6
      senior general surgery residents at 2 physical locations. A 24-question (36
      point) examination was administered before and after the workshop. RESULTS: The
      workshop produced significant improvements in the mean test scores between the
      pretests and posttests (17.67 to 23.67, P <.02). We found no differences between
      residents who were with the instructor and those at the remote location. Six
      month delayed testing demonstrated complete retention of new knowledge.
      CONCLUSIONS: The teleimmersive environment enabled surgeons to overcome some of
      the barriers to teaching complex surgical anatomic principles. Using
      teleimmersive environments, surgical educators and trainees can interact from
      locations worldwide using virtual anatomic information to achieve their
      educational goals.

PMID- 12219024
TI  - Learning and memory is preserved after induced asanguineous hyperkalemic
      hypothermic arrest in a swine model of traumatic exsanguination.
AB  - BACKGROUND: Induced asanguineous hypothermic metabolic arrest (suspended
      animation) could provide valuable time to repair major vascular injuries if
      safely induced in patients with trauma. We report a novel method of doing this in
      a swine model of uncontrolled lethal hemorrhage (ULH) that resulted in
      preservation of learning ability and memory. METHODS: Yorkshire swine (100 to 125
      lb) underwent ULH before rapid intra-aortic infusion of a hypothermic (4 degrees
      C), hyperkalemic (70 mEq/L) organ preservation solution by a left thoracotomy.
      Cooling continued until core temperature reached 10 degrees C, and this was
      maintained for 60 minutes using low-flow cardiopulmonary bypass. Vascular
      injuries were repaired during this state of suspended animation, which was then
      reversed, and the animals were observed for 6 weeks. Cognitive functions were
      tested by training animals to retrieve food from color-coded boxes.
      Postoperatively, the ability to remember this task and a 75-point objective
      neurologic scale were used to test neurologic function. In experiment I, ULH was
      caused by lacerating thoracic aorta (n = 9). Five preoperatively untrained
      animals were trained to perform the task and compared with control animals (n =
      15), and 4 preoperatively trained animals were tested for memory retention
      postoperatively. In experiment II, ULH was induced by creating an iliac artery
      and vein injury (n = 15). Animals were kept in shock for 15, 30, and 60 minutes
      before the induction of hypothermia. RESULTS: In experiment I, surviving animals
      (7/9) were neurologically intact, and their capacity to learn new skills was no
      different than for control animals. All pretrained animals demonstrated complete
      memory retention. In experiment II, survival with 15, 30, and 60 minutes of shock
      were 80%, 60%, and 80%, respectively. All animals (except 1) in the 60-minute
      group were neurologically intact and displayed normal learning capacity.
      CONCLUSIONS: Induction of hypothermic metabolic arrest (by thoracotomy) for
      repair of complex traumatic injuries is feasible with preservation of normal
      neurologic function, even after extended periods of shock from an intra-abdominal
      source of uncontrolled hemorrhage.

PMID- 12219025
TI  - Interferon-gamma gene polymorphisms and the development of sepsis in patients
      with trauma.
AB  - BACKGROUND: The outcome of patients with trauma does not always correlate with
      injury severity or premorbid health status. This study evaluates the relationship
      between polymorphisms in the first intron of the interferon-gamma gene and the
      development of sepsis after trauma. METHODS: DNA was extracted from peripheral
      leukocytes of patients with trauma and an injury severity score of 16 or greater.
      Data collected included demographics, injury mechanism, injuries sustained,
      development of sepsis, and outcome. A previously identified cytosine/adenine
      repeated polymorphism was amplified, alleles/genotypes identified, and the
      results correlated with patient outcome. RESULTS: Sixty-one patients were
      evaluated. Thirty patients (49%) became septic. The injury severity score, race,
      age, and gender distribution was similar for both the septic and nonseptic
      groups. Six alleles and 10 genotypes were identified. Alleles C (34%) and D (52%)
      were the most common. Patients who were septic had a 62% chance of having a D
      allele (P =.06), whereas they had only a 29% chance of having a C allele.
      Homozygotes for allele D (DD) were the most likely to become septic (65%).
      CONCLUSIONS: Homozygotes for the D allele (DD) of the interferon-gamma gene have
      an increased chance of developing sepsis after traumatic injury compared with
      other allelic combinations. This supports the hypothesis that genetic composition
      plays a role in patient outcome.

PMID- 12219026
TI  - Identification of mitogen-activated protein kinase kinase as a chemoresistant
      pathway in MCF-7 cells by using gene expression microarray.
AB  - BACKGROUND: Components of the mitogen-activated protein kinase (MAPK) cascade
      have been implicated in apoptotic regulation. This study used gene expression
      profiling analysis to identify and implicate mitogen-activated protein kinase
      kinase (MEK5)-BMK1 (big mitogen-activated kinase-1)/extracellular signal related
      protein kinase (ERK5) pathway as a novel target involved in chemoresistance.
      METHODS: Differential gene expression between apoptotically sensitive (APO+) and
      apoptotically resistant (APO-) MCF-7 cell variants was determined by using
      microarray and confirmed by reverse transcriptase- polymerase chain reaction (RT
      PCR). An apoptotic/viability reporter gene assay was used to deter-mine the
      effects of the transfection of a dominant-negative mutant of BMK1 (BMK1/DN) in
      conjunction with apoptotic-inducing agents (etoposide, tumor necrosis factor
      alpha [TNF], or TNF-related apoptosis-inducing ligand [TRAIL]), with or without
      phorbol ester (PMA). RESULTS: Of the 1186 genes detected through microarray
      analysis, MEK5 was increased 22-fold in APO- cells. Overexpression of MEK5 was
      confirmed by using RT-PCR analysis. Expression of BMK1/DN alone resulted in a
      dose-dependent increase in cell death versus control (P <.05). In addition,
      BMK1/DN enhanced the sensitivity of MCF-7 cells to treatment-induced cell death
      (P <.05). The ability of PMA to partially suppress TRAIL- and TNF-induced cell
      death was inhibited by BMK1/DN. However, only TRAIL-induced activity suppression
      reached statistical significance (P <.05). CONCLUSIONS: The overexpression of
      MEK5 in APO- MCF-7 breast carcinoma cells shows that this MAPK signaling protein
      represents a potent survival molecule. Molecular inhibition of MEK5 signaling may
      represent a mechanism for sensitizing cancer cells to chemotherapeutic regimens.

PMID- 12219027
TI  - 17-Beta-estradiol protects the liver against warm ischemia/reperfusion injury and
      is associated with increased serum nitric oxide and decreased tumor necrosis
      factor-alpha.
AB  - BACKGROUND: Ischemia/reperfusion injury (I/R injury) to the liver can occur in
      low-flow states associated with trauma and shock and surgical procedures such as
      liver transplantation. Recent studies have shown that the administration of the
      female sex hormone 17-beta-estradiol after trauma-hemorrhage in animals restores
      depressed cardiac, hepatocellular, and immune functions. In this study we
      evaluated the effects of 17-beta-estradiol on I/R injury to the liver. METHODS:
      The medial lobe of the liver in normal male C57BL/6 mice was clamped at its base
      for 90 minutes. 17-Beta-estradiol was given 1 hour before I/R injury at 40 and
      4000 microg/kg intraperitoneally. Biochemical analysis was performed, and liver
      biopsy specimens were obtained at 24 hours. RESULTS: A dose-dependent reduction
      in aspartate aminotransferase level was observed in animals (n = 8) given
      estradiol (243 +/- 23 IU/L) compared with saline-treated animals (902 +/- 42
      IU/L, P <.001). The majority (90%) of the cytoprotective effect of estradiol was
      reverted by ICI 182,780 (a potent estrogen receptor antagonist). A significant
      increase in serum nitric oxide (NO) level was observed in animals given estradiol
      compared with controls; the effect was reversed by ICI 182,780 and N-nitro-L
      arginine-methyl ester (an inhibitor of NO synthesis). A reduction in serum tumor
      necrosis factor-alpha was observed after injury in animals given estradiol
      compared with controls (30.2 +/- 11.1 vs 75.8 +/- 17.2 pg/mL, P <.001). Estradiol
      treatment significantly reduced liver necrosis, disintegration of hepatic cords,
      and neutrophil infiltration in an estrogen receptor-dependent manner.
      CONCLUSIONS: Estradiol administration significantly reduced injury after I/R to
      the liver, an effect that is mainly receptor-mediated and is associated with
      increased serum NO, decreased TNF-alpha, and decreased number of neutrophils in
      liver biopsy specimens. Estrogen therapy may be important in clinical conditions
      associated with I/R injury to the liver.

PMID- 12219028
TI  - Resistance to transforming growth factor-beta occurs in the presence of normal
      Smad activation.
AB  - BACKGROUND: Resistance to the growth inhibitory actions of transforming growth
      factor-beta (TGF-beta) is common in human cancers. This resistance can be a
      result of decreased expression of TGF-beta receptors. Downregulation of c-Myc by
      TGF-beta is critical for TGF-beta-mediated growth inhibition. In this study we
      hypothesized that decreased TGF-beta receptor expression leads to reduced Smad
      signaling and overexpression of c-Myc in intestinal epithelial (RIE) and
      transformed intestinal epithelial cells (RIE-Tr) cells. METHODS: RIE (TGF-beta
      sensitive) and RIE-Tr (TGF-beta-resistant) cells were treated with and without
      fetal bovine serum and TGF-beta. Western blot analysis was performed to detect
      levels of c-Myc, Smad2, Smad4, and phosphorylated Smad2 in RIE and RIE-Tr cells.
      Smad complex formation was analyzed by immunoprecipitation-coupled Western
      blotting. RESULTS: c-Myc is overexpressed in RIE-Tr cells. TGF-beta-mediated
      downregulation of c-Myc is abrogated in RIE-Tr cells. Smad expression and
      activation is normal in RIE-Tr cells. We found that Smad2, Smad4, and Smad6
      expression remained constant in RIE and RIE-Tr cells with or without serum or TGF
      beta treatment. In addition, TGF-beta induced similar Smad2 phosphorylation and
      Smad complex formation in both RIE and RIE-Tr cells. CONCLUSIONS: Our data
      demonstrate that Smad signaling is preserved in the face of decreased TGF-beta
      receptor levels. We also demonstrate that Smad signaling is not sufficient for
      TGF-beta-mediated c-Myc repression.

PMID- 12219029
TI  - The signaling protein Rho is necessary for vascular smooth muscle migration and
      survival but not for proliferation.
AB  - BACKGROUND: The small GTPase Rho has been implicated in a variety of cellular
      processes. Vascular smooth muscle cell (SMC) migration, proliferation, and
      apoptosis are important events that contribute to the formation of intimal
      hyperplasia. To better understand the importance of Rho in intimal hyperplasia,
      we evaluated the necessity of Rho for these 3 cellular processes. METHODS: We
      used for these studies a recombinant C3 exoenzyme (C3), which selectively
      adenosine diphosphate-ribosylates and, thus, functionally inactivates Rho. SMC
      migration was determined by scratch and modified Boyden chamber assays,
      proliferation by tritiated-thymidine incorporation, and apoptosis by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling. RESULTS:
      Pretreatment of human SMC with C3 overnight resulted in adenosine diphosphate
      ribosylation and inactivation of Rho. Inactivation of Rho completely eliminated
      SMC migration in response to platelet-derived growth factor (PDGF)-AB.
      Furthermore, C3 blocked phosphorylation of focal adhesion kinase, tensin, and
      paxillin, which are essential for cellular migration. In contrast, C3 did not
      significantly affect DNA synthesis in response to PDGF-AB or activation of
      mitogen-activated protein kinase, a signaling mediator of PDGF-stimulated
      proliferation. However, prolonged inactivation of Rho by C3 induced apoptosis of
      SMC. CONCLUSIONS: The small GTPase Rho is necessary for vascular SMC migration
      and cell survival but not for proliferation. Manipulation of Rho might have
      therapeutic value in modulating intimal hyperplasia.

PMID- 12219030
TI  - Heparanase-1 expression is associated with the metastatic potential of breast
      cancer.
AB  - BACKGROUND: Metastasis of malignant breast cells is in part mediated through
      degradation of the extra-cellular matrix by proteolysis, enabling malignant cells
      to migrate through the surrounding stroma. Heparanase-1 (HPR1) is an
      endoglycosidase that specifically degrades the heparan sulfate (HS) moiety of
      proteoglycans, a component of the extracellular matrix and basement membrane.
      METHODS: Fifty-one primary breast tumors, 13 lymph node metastases, 4 ductal
      carcinoma in situ, 7 benign, and 5 normal specimens were examined for HPR1
      expression using immunohistochemical staining. The functional role of HPR1
      expression was determined by examining HS deposition using immunofluorescence
      staining. RESULTS: Sixteen of 30 breast carcinomas (53%) with sentinel node
      metastasis expressed HPR1. In contrast, only 5 of 21 nonmetastatic primary breast
      carcinomas (23%) were HPR1 positive. Eighteen of 30 breast carcinomas between 1
      and 5 cm expressed HPR1, compared with 3 of 21 HPR1-positive specimens in tumors
      < or =1 cm. Statistical analysis revealed that HPR1 expression was associated
      with breast tumor metastases (P =.04) and primary tumors between 1 and 5 cm (P
      =.002). Ninety percent of HPR1-positive tumors lacked HS deposition, suggesting
      an inverse correlation between HPR1 expression and HS deposition. CONCLUSIONS:
      HPR1 expression correlates with the lack of HS deposition and with the metastatic
      potential of breast cancers. The frequency of HPR1 is significantly higher in
      breast tumors between 1 and 5 cm than in tumors < or =1 cm.

PMID- 12219031
TI  - Complement regulatory protein CD59 involves c-SRC related tyrosine
      phosphorylation of the creatine transporter in skeletal muscle during sepsis.
AB  - BACKGROUND: Myocellular creatine (Cr) uptake is predominantly governed by the
      creatine transporter (CreaT) and plays a pivotal role in skeletal muscle energy
      metabolism. The CreaT belongs to a neurotransmitter transporter family that is
      functionally regulated by protein tyrosine kinase induced tyrosine
      phosphorylation. Recently, complement regulatory protein CD59 has been found not
      only to protect host tissue from C5b-9 complex attack that occurs in sepsis but
      also to initiate the activation of Src family kinase and tyrosine phosphorylation
      of its downstream proteins. The purpose of this study was to determine the
      association between myocellular free Cr, c-Src related tyrosine phosphorylation
      of the CreaT, and CD59 during sepsis. METHODS: Male Sprague-Dawley rats (250 to
      300 g) were randomized to undergo cecal ligation and puncture (CLP) or sham
      operation. Fast-twitch gastrocnemius muscles were harvested 24 hours after
      operation. Myocellular free Cr levels were measured by high-performance liquid
      chromatography. Combination of protein immunoprecipitation with Western blotting
      was used to assess tyrosine phosphorylation status of the CreaT and the
      association between CD59, c-Src, and CreaT. RESULTS: Myocellular free Cr levels
      were 70% greater after CLP. Tyrosine phosphorylation of the CreaT was
      significantly increased after CLP as compared to sham operation. Tyrosine
      phosphorylated c-Src (Tyr-416) in the CreaT-c-Src immune complex was 24% higher
      after CLP. Sepsis also increased protein expression of tyrosine phosphorylated c
      Src (Tyr-416) or CreaT in the CD59-c-Src or CD59-CreaT complex by 20% or 30%,
      respectively. CONCLUSIONS: During sepsis, an increase in myocellular free Cr
      levels is associated with enhanced tyrosine phosphorylation of the CreaT, which
      is likely induced by active c-Src. CD59 is physically associated with both c-Src
      and CreaT, which suggests that CD59 may participate in the regulation of
      myocellular Cr metabolism via the CreaT during sepsis.

PMID- 12219032
TI  - The effect of prolonged euglycemic hyperinsulinemia on lean body mass after
      severe burn.
AB  - BACKGROUND: The hypermetabolic response to burn increases protein catabolism.
      Euglycemic hyperinsu-linemia with exogenous insulin maintains muscle protein by
      continued stimulation of net protein synthesis. Our aim was to determine the
      effect of euglycemic hyperinsulinemia over the entire hospitalization on muscle
      anabolism by investigating lean body mass (LBM) as the primary endpoint. METHODS:
      Eighteen subjects between the ages of 2 and 18 with burns of more than 40% were
      prospectively randomized into 2 groups, a control (n = 9) and a treatment group
      (n = 9). The treatment group was given continuous intravenous insulin at a rate
      of at least 1.5 microU/kg/min to maintain serum glucose levels between 100 to 140
      mg/dL. Treatment was instituted 24 to 48 hours after arrival and continued until
      the patient's injury was 95% healed. All patients received continuous enteral
      feeding. Patients underwent body composition studies by dual-energy x-ray
      absorptiometry (DEXA) scan on postoperative day 6 after initial burn excision and
      when 95% healed. RESULTS: Nutritional intakes were not different between groups.
      In the control, subjects continued catabolism resulted in peripheral muscle
      wasting and centripetal obesity with diminished truncal LBM. The treatment group
      had improvement in lean body mass (P =.004) and bone mass (P =.025). The
      treatment group also had less peripheral muscle wasting with overall increases in
      upper/lower extremity LBM (P =.005). Hospital length of stay in days per percent
      of total body surface area burned was decreased in the insulin group (control =
      1.03 +/- 0.1 vs 0.7 +/- 0.9 for insulin patients; P <.05). CONCLUSIONS:
      Euglycemic hyperinsulinemia throughout the hospital course mitigates muscle
      catabolism and preserves lean body mass.

PMID- 12219033
TI  - Living donor liver transplantation in adults: recent advances and results.
AB  - BACKGROUND: Living donor liver transplantation (LDLT) is now widely performed for
      adult patients to resolve the critical shortage of organs from cadavers. The
      objective of this study was to analyze the experience of a single center with
      adult LDLT. METHODS: Eighty-two consecutive LDLT procedures for adults were
      divided into 3 groups according to the transplant era and the preoperative
      condition and indications: all patients between 1996 and 1999 (Group 1, n = 30),
      good-risk patients between 2000 and November 2001 (Group 2, n = 28), and poor
      risk patients (Group 3, n = 24). Up to 1999, left liver graft was used for all
      patients. Thereafter, right liver was selected only for poor-risk patients.
      Preoperative status, morbidity, hospital duration, and postoperative graft
      function and survival rate were examined and compared among the groups. RESULTS:
      Comparison of groups 1 and 2 revealed a significant difference in the hospital
      duration and the survival rate. In contrast, the short-term surgical results were
      comparable between groups 2 and 3. The 2-year survival rates were 84%, 100%, and
      88%, respectively. CONCLUSIONS: The present results suggest that our graft
      selection criteria are acceptable. A small graft can provide satisfactory results
      when used in good-risk patients and a right liver graft may be beneficial in poor
      risk patients.

PMID- 12219034
TI  - Ionizing radiation potentiates the antitumor efficacy of oncolytic herpes simplex
      virus G207 by upregulating ribonucleotide reductase.
AB  - BACKGROUND: Replication-competent herpes simplex virus-1 (HSV-1) mutants have an
      oncolytic effect on human and animal cancers. The aim of this study was to
      determine whether G207, an HSV-1 mutant, can be combined with ionizing radiation
      (IR) to increase antitumor activity while decreasing treatment-associated
      toxicity. METHODS: This study was performed by using G207, a replication
      competent HSV-1 mutant deficient in viral ribonucleotide reductase (RR) and the
      gamma(1)34.5 neurovirulence protein. The antitumor activity of G207 or IR was
      tested against HCT-8 human colorectal cancer cells in vitro and in an in vivo
      mouse subcutaneous tumor model. RESULTS: We demonstrated that G207 has
      significant oncolytic effect on HCT-8 cells in vitro in a cytotoxicity assay and
      in vivo in a mouse flank tumor model and that these effects are improved with low
      dose IR. We further illustrated that the increased tumoricidal effect is
      dependent on the up-regulation of cellular RR by IR measured by a functional
      bioassay for RR activity. Chemical inhibition of RR by hydroxyurea abrogates the
      enhanced effect. In contrast to G207, R3616, the parent virus of G207 that
      expresses functional RR, does not exhibit enhanced oncolysis when combined with
      IR. CONCLUSIONS: These data encourage clinical investigation of combination
      radiation therapy and HSV oncolytic therapy.

PMID- 12219035
TI  - Impaired activation of mitogen-activated protein kinases after hemorrhagic shock.
AB  - BACKGROUND: Patients sustaining major trauma are at risk of developing organ
      dysfunction. We have previously shown that resuscitated hemorrhagic shock primes
      for increased lung injury in response to lippolysaccharide (LPS), in part by
      preventing upregulation of the counterinflammatory cytokine IL-10. Because the
      mitogen-activated protein kinase (MAPK) family is known to participate in LPS
      signaling, we hypothesized that altered upstream signaling through these kinases
      might contribute to impaired LPS-simulated IL-10 release after shock and
      resuscitation. METHODS: Rats were bled to a mean arterial pressure of 40 mm Hg
      and maintained for 1 hour, then resuscitated. Alveolar macrophages were retrieved
      at the end of resuscitation and exposed to LPS (0.5 microg/mL). Western blotting
      for p38, extracellular-regulated protein kinase, and c-Jun NH2-terminal kinase
      was performed on whole cell lysates. In some studies, the alveolar macrophages
      were preincubated with the p38 inhibitor or the extracellular-regulated protein
      kinase inhibitor before LPS stimulation. IL-10 levels were measured by enzyme
      linked immunosorbent assay. RESULTS: LPS caused an early activation in all
      members of the MAPK family, whereas antecedent shock both delayed and attenuated
      the LPS induction. To discern whether this reduction in LPS-stimulated MAPK
      activation after shock might contribute to reduced IL-10, specific inhibitors
      were used. Inhibition of p38 MAPK completely inhibited LPS-induced IL-10
      production, whereas blockade of extracellular-regulated protein kinase pathway
      had no effect. CONCLUSIONS: Shock resuscitation impairs LPS-induced activation of
      the members of the MAPK family. For the critical counterinflammatory cytokine IL
      10, inhibition of p38 activation appears to contribute to the reduced levels of
      this cytokine in response to LPS. This study provides in vitro evidence for
      altered signaling through p38 MAPK, as a mechanism leading to failed upregulation
      of a counterinflammatory cytokine, and thus the propagation of an unrestrained
      proinflammatory state. Restoration of normal signaling may represent an effective
      strategy to reverse this effect.

PMID- 12219036
TI  - Production of interferon-gamma by tumor-sensitized T cells is essential for
      interleukin-12-induced complete tumor eradication.
AB  - BACKGROUND: Interferon-gamma (IFN-gamma) is essential for eradication of
      established large tumors by interleukin-12 (IL-12), but the critical source of
      IFN-gamma has not been defined. Adoptive transfer of T cells into T cell
      deficient mice allows for evaluation of the role of T cells and T cell production
      of IFN-gamma in the antitumor immune response. METHODS: Wild-type C57BL/6, IL-12
      receptor-beta1 knockout (IL-12Rbeta1 KO), IFN-gamma knockout (IFN-gamma KO), and
      IFN-gamma receptor-alpha knockout (IFN-gammaRalpha KO) mice were immunized and
      used as donors for adoptive transfer. Transfer of either splenocytes or CD90(+) T
      cells was performed into recipient T cell receptor-beta knockout (TCRbeta KO) and
      IFN-gamma/TCRbeta double knockout mice bearing 14-day subcutaneous MCA207 tumors.
      Half of the mice were treated with IL-12, and cure rates were compared. RESULTS:
      Transfer of either 1/4 immunized spleen equivalent or 10(7) immunized T cells
      into both TCRbeta KO and IFN-gamma/TCRbeta KO mice resulted in 80% to 100% cure
      when given with IL-12. However, transfer of 10(7) immunized T cells from IFN
      gamma KO mice into TCRbeta KO mice was ineffective with or without IL-12. T cell
      response to IL-12, but not IFN-gamma, was required for tumor regression.
      CONCLUSIONS: Production of IFN-gamma by IL-12-responsive tumor-sensitized T cells
      is both necessary and sufficient for complete tumor eradication induced by IL-12.
      T cells are the source, but not the target, of IFN-gamma during tumor regression.

PMID- 12219037
TI  - Intraischemic hypothermia differentially modulates oxidative stress proteins
      during mesenteric ischemia/reperfusion.
AB  - BACKGROUND: Thoracoabdominal aortic aneurysm repair requires obligatory
      mesenteric ischemia/reperfusion (I/R), eliciting an inflammatory response
      resulting in gut dysfunction and remote organ injury. Therapeutic hypothermia has
      been advocated for organ protection (ie, brain, spinal cord, and kidneys) during
      extensive aortic operation, and it has also been shown to differentially modulate
      proinflammatory gene transcription in the central nervous system. In other I/R
      models, nuclear factor Kappa-B (NF-(kappa)B) and inducible nitric oxide synthase
      (iNOS) worsen while heme oxygenase-1 (HO-1) protects against injury. We examined
      the effects of regional intraischemic hypothermia on mesenteric I/R-induced
      mucosal injury, NF-kappaB activation, and expression of iNOS and HO-1. METHODS:
      Sprague-Dawley rats underwent sham laparotomy or superior mesenteric artery
      occlusion for 45 minutes with or without topical hypothermia (15 degrees -20
      degrees C). Intestinal epithelial permeability to (14)C inulin was assessed at 6
      hours of reperfusion. In a separate set of experiments, biopsies of the ileum
      were obtained at 6 hours of reperfusion for: 1) mucosal histologic injury
      assessed by a blinded observer; 2) NF-kappaB activation by electrophoretic
      mobility shift assay; and 3) iNOS and HO-1 protein expression by immunoblot.
      RESULTS: Mesenteric I/R significantly increased intestinal permeability to (14)C
      inulin, histologic injury, activation of NF-kappaB, and iNOS and HO-1 expression
      when compared with sham control rats. In contrast, rats treated with
      intraischemic topical hypothermia exhibited intestinal permeability comparable
      with sham control rats, and reduced histologic injury. In addition, hypothermia
      prevented the activation of NF-kappaB and iNOS expression, but had no effect on
      HO-1 expression. CONCLUSIONS: On the basis of these observations, we conclude
      that therapeutically applied intraischemic hypothermia protects the gut during
      mesenteric I/R. In addition, hypothermia prevented NF-kappaB activation while
      differentially modulating expression of the oxidative stress proteins iNOS and HO
      1 in response to mesenteric I/R.

PMID- 12219038
TI  - A serum factor after intestinal resection stimulates epidermal growth factor
      receptor signaling and proliferation in intestinal epithelial cells.
AB  - BACKGROUND: In vivo, intestinal adaptation after massive small bowel resection
      (SBR) requires a functional epidermal growth factor (EGF) receptor (EGFR). In
      vitro studies have shown that serum from mice after SBR induces rat intestinal
      epithelial cells to proliferate. This study tested the hypothesis that the
      proliferative response to SBR serum is mediated by EGFR signaling. METHODS: Serum
      was collected from male Sprague-Dawley rats 7 days after 75% SBR or sham
      operation. Rat intestinal epithelial cells were incubated in the presence of sham
      or SBR serum. Total EGFR expression and phosphorylation of several EGFR
      downstream pathways were determined by Western blotting. In other experiments, a
      specific EGFR inhibitor (ZD1839) was added and cell growth determined over 5
      days. RESULTS: SBR serum significantly increased total EGFR expression (3-fold)
      over sham operation and consistently activated the phosphatidylinositol 3-kinase
      pathway. Furthermore, SBR serum markedly augmented rat intestinal epithelial cell
      growth, an effect that was abolished by EGFR inhibition. CONCLUSIONS: SBR serum
      contains a factor or factors that stimulates proliferation of intestinal
      epithelial cells by an EGFR and phosphatidylinositol 3-kinase signaling
      mechanism. These data recapitulate in vivo studies supporting the hypothesis that
      EGFR is a central mediator of postresection intestinal adaptation. This in vitro
      model may provide a novel means to gain insight into the pathophysiology of
      intestinal adaptation.

PMID- 12219039
TI  - Bone marrow-derived liver stem cell and mature hepatocyte engraftment in livers
      undergoing rejection.
AB  - BACKGROUND: The definitive therapy for end-stage liver disease is orthotopic
      liver transplantation (OLT). However, rejection is still a major cause of
      mortality and morbidity following OLT. Hepatocyte transplantation has been used
      experimentally to treat liver diseases. The aim of this study was to investigate
      whether bone marrow-derived liver stem cells (BDLSC) and mature hepatocytes could
      repopulate transplanted livers undergoing rejection. METHODS: OLT was carried out
      from D'Agouti (C3-positive female) into Lewis (C3-negative female) rats. BDLSC
      were transplanted from Lewis (male) into livers of D'Agouti (female) rats. Group
      A (n = 9) received intraportal normal saline. Groups B (n = 9) and C (n = 9)
      underwent intraportal transplantation of mature hepatocytes (Lewis female, 0.75 x
      10(7)) and DBLSC (Lewis male, 5 x 10(4)) respectively. All groups received
      subtherapeutic immunosuppression (Cyclosporin 0.25 mg/kg/d) for 13 days. Liver
      repopulation was assessed using immunohistochemistry (C3 antigen-negative cells),
      in-situ hybridization, (Y-chromosome-positive BDLSC) and histologic assessment
      (hematoxylin and eosin) for rejection. RESULTS: BDLSC and mature hepatocytes
      repopulated 62 +/- 12.3% and 2.5 +/- 1.7% of rejecting livers, respectively.
      BDLSC demonstrated formation of hepatic lobules and portal triads with little
      evidence of rejection 36 days after discontinuation of immunosuppression.
      CONCLUSIONS: BDLSC can repopulate livers undergoing severe rejection. Moreover,
      BDLSC can differentiate into hepatocytes and cholangiocytes. This finding may
      have important clinical implications.

PMID- 12219040
TI  - 25% Albumin modulates adhesive interactions between neutrophils and the
      endothelium following shock/resuscitation.
AB  - BACKGROUND: Polymorphonuclear neutrophil (PMN) sequestration in the lung is a
      hallmark of acute respiratory distress syndrome (ARDS). We have shown that 25%
      Albumin (A25) resuscitation attenuates lung injury after hemorrhagic shock and
      lipopolysaccharide (LPS) exposure by reducing lung leukosequestration. We
      hypothesize that this protective property is mediated by alteration of neutrophil
      endothelial cell adhesive interactions. MATERIALS AND METHODS: A 2-hit rodent
      model of shock resuscitation was used. CD11b and L-selectin were measured using
      flow cytometry in rat and human neutrophils ex vivo. Intercellular adhesion
      molecule-1 (ICAM-1) levels were measured by Northern blot and
      immunohistochemistry. RESULTS: Resuscitation with A25 attenuated the increase in
      PMN CD11b expression in Ringer's lactate (RL) resuscitated animals at end
      resuscitation and at 4-hour post-LPS. While PMN L-selectin levels remained stable
      in RL treated animals, A25 resuscitation resulted in a significant decrease in
      surface L-selectin expression at 4-hour post-LPS. ICAM-1 lung endothelial cell
      mRNA, was increased in RL resuscitated animals, however reduced with A25 use by
      51%. The LPS induced ICAM-1 endothelial cell protein expression was also
      prevented with A25 resuscitation. Antioxidant property of albumin was shown to
      play a critical role in altering CD11b expression. CONCLUSIONS: The A25 exerts
      its lung-protective activity at various levels including altering the interaction
      between neutrophils and endothelial cells via suppressed expression of adhesion
      molecules. These findings suggest a novel role for A25 as an anti-inflammatory
      agent in PMN-mediated diseases such as ARDS.

PMID- 12219041
TI  - The cost-effectiveness of a "quick-screen" program for abdominal aortic
      aneurysms.
AB  - BACKGROUND: The incidence of abdominal aortic aneurysm (AAA) is increasing, and
      the prognosis of ruptured AAA remains dismal. Early diagnosis and intervention
      are crucial. We designed this study to determine whether selected population
      screening with a brief "quick-screen" ultrasound could be cost-effective.
      METHODS: A series of 25 patients with risk factors for AAA were evaluated in a
      blinded fashion by a quick-screen ultrasound and a full conventional study. Times
      and accuracy for the 2 approaches were compared. An analysis of the cost
      effectiveness of screening for AAA was then performed using a Markov model. We
      determined the long-term survival in quality-adjusted life years and lifetime
      costs for a hypothetical cohort of 70-year-old males undergoing either AAA
      screening or not. Our measure of outcome was the cost-effectiveness ratio (CER).
      RESULTS: The average time for a quick screen was one-sixth that of a conventional
      study (4 vs 24 minutes). The accuracy of the quick screen was 100%. In our base
      case analysis, screening for AAA was cost-effective with a CER of $11,215.
      Society usually is willing to pay for interventions with CER of less than $60,000
      (eg, CER for coronary artery bypass grafting, $9500; breast cancer screening,
      $16,000). In sensitivity analysis, reducing the cost of screening from $259
      (approximate Medicare reimbursement) to $40 (the quick screen) improved the CER
      to $6850. Moreover, screening populations with increased prevalence of AAA (eg,
      male with family history [18%]) further improved the CER. CONCLUSIONS: Our
      analysis demonstrates that ultrasound screening for AAA should be offered to all
      males above the age of 60. Widespread screening for AAA should be adopted and
      reimbursed by Medicare and other insurers.

PMID- 12219042
TI  - Gram-negative bacteria killed by complement are associated with more severe
      biliary infections and produce more tumor necrosis factor-alpha in sera.
AB  - BACKGROUND: We previously showed that gallstones contain bacteria and that
      illness severity correlates with bacterial presence. This study examined
      virulence differences of gram-negative biliary bacteria. METHODS: Gallstones and
      bile were cultured, and sera obtained, from 210 patients. Infection severity was
      staged as: none-no clinical infection; moderate-fever, leukocytosis; or severe
      bacteremia, cholangitis, hypotension, abscess, or organ failure. Gram-negative
      biliary bacteria were tested against patient (and control) serum for complement
      mediated bacterial killing and induction of tumor necrosis factor-alpha
      (TNFalpha) production (using cultured monocytes) with and without sera. These
      results were correlated with infection severity. RESULTS: A total of 98 (47%)
      patients had biliary bacteria. Infection severity distribution was none, 29%;
      moderate, 35%; and severe, 36%. Gram-negative organisms killed by complement were
      associated with more severe infections as follows: 13%, none; 60%, moderate; and
      88%, severe infections (P =.024 and P <.0001, respectively vs none, chi-square
      test). TNFalpha production in sera increased 182 pg/mL with complement resistant
      bacteria, but increased 546 pg/mL with bacteria killed by complement (P <.0001,
      killed vs not killed, Student's t test). E coli and Klebsiella were the most
      virulent bacterial species. They were cultured from blood, usually killed by
      complement, and had the largest increase in TNFalpha production in sera.
      CONCLUSIONS: Gram-negative biliary bacteria killed by complement (as opposed to
      complement-resistant) were associated with more serious biliary infections
      including bacteremia and induced more TNFalpha production in sera. This suggests
      a potential role for complement activation and cytokine production in biliary
      sepsis.

PMID- 12219043
TI  - Issues in the recruitment and success of women in academic surgery.
AB  - BACKGROUND: We undertook a national survey of male and female academic surgeons
      to identify issues and perceptions surrounding the success of women in surgery.
      DATA AND METHODS: A previously tested survey instrument was sent to 772 female
      and 994 male academic surgeons. Responses were entered and compared across a
      number of categories using descriptive statistics and t tests. RESULTS: Women
      report similar objective experience, but have very different perceptions of the
      issues in academic surgery than do men. Differences include access to
      collaboration and support, issues in balancing family and work life, and to what
      degree perceptions are changing. DISCUSSION: If we are to recruit and retain the
      best possible faculty into academic surgery, it will be necessary to further
      understand women's perceptions of their role in academic surgery and to address
      obstacles that exist for both men and women.

PMID- 12219044
TI  - Why physicians are certified by boards.

PMID- 12219045
TI  - Why maintenance of certification?

PMID- 12219046
TI  - Shooting at a moving target: natural history studies and the rapidly improving
      state of anti-HIV treatment.

PMID- 12219047
TI  - Unexpected infant death: occult cardiac disease and sudden infant death syndrome
      how much of an overlap is there?

PMID- 12219048
TI  - Screening for exercise-induced asthma.

PMID- 12219049
TI  - Bones benefit from better biochemical control in type 1 glycogen storage disease.

PMID- 12219050
TI  - Biological and chemical terrorism.

PMID- 12219051
TI  - Incidence of cardiac abnormalities in children with human immunodeficiency virus
      infection: The prospective P2C2 HIV study.
AB  - OBJECTIVE: To describe the 5-year cumulative incidence of cardiac dysfunction in
      human immunodeficiency virus (HIV)-infected children. STUDY DESIGN: We used a
      prospective cohort design, enrolling children at 10 hospitals. Group I included
      205 vertically HIV-infected children enrolled at a median age of 1.9 years. Group
      II consisted of 600 HIV-exposed children enrolled prenatally or as neonates, of
      whom 93 were ultimately HIV-infected. The main outcome measures were
      echocardiographic indexes of left ventricular dysfunction. RESULTS: In group I,
      the 5-year cumulative incidence of left ventricular fractional shortening </=25%
      was 28.0%. The 5-year incidence of left ventricular end-diastolic dilatation was
      21.7%, and heart failure and/or the use of cardiac medications 28.8%. The
      mortality rate 1 year after the diagnosis of heart failure was 52.5% [95% CI,
      30.5-74.5]. Within group II, the 5-year cumulative incidence of decreased
      fractional shortening was 10.7% in the HIV-infected compared with 3.1% in the HIV
      uninfected children (P =.01). Left ventricular dilation, heart failure, and/or
      the use of cardiac medications were more common in infected compared with
      uninfected children. CONCLUSIONS: During 5 years of follow-up, cardiac
      dysfunction occurred in 18% to 39% of HIV-infected children and was associated
      with an increased risk of death. We recommend that HIV-infected children undergo
      routine echocardiographic surveillance for cardiac abnormalities.

PMID- 12219052
TI  - Cardiac pathology in sudden unexpected infant death.
AB  - OBJECTIVES: To determine the spectrum of cardiac pathology and circumstances of
      death in infants with sudden unexpected death and to define the impact of sudden
      cardiac deaths to overall sudden infant death. STUDY DESIGN: Retrospective
      analysis of all autopsies of infants with sudden death 7 days to 2 years of age
      between January 1987 and December 1999 in the province of Quebec (Canada).
      RESULTS: Eighty-two cases of sudden death with cardiac pathology were found,
      representing 10% of the total number of sudden infant deaths. A structural
      malformation was present in the majority of cases (54%); however, cardiac
      pathology in anatomically normal hearts was also common (46%). Most (64%)
      anatomic malformations were detected before death compared with 13% of
      nonstructural heart disease. Although a major proportion of children were found
      dead during sleep, a significant number were described as being awake at time of
      death (32%). CONCLUSIONS: Heart disease is present in a significant percentage of
      autopsies of infants with sudden death. Structural heart malformations
      predominate, although nonstructural pathologic features of the heart are common
      and usually unrecognized before an autopsy is performed. Cardiac pathologic
      features are frequent when the child is witnessed to be awake at the time of
      sudden death.

PMID- 12219053
TI  - Effectiveness of screening examinations to detect unrecognized exercise-induced
      bronchoconstriction.
AB  - OBJECTIVE: To determine if a physician-administered physical examination and
      screening questionnaire accurately detects exercise-induced bronchoconstriction
      (EIB) in adolescent athletes. STUDY DESIGN: Cross-sectional study of 256
      adolescents participating in organized sports from 3 suburban high schools. The
      number of persons screened positive for EIB by physical examination and
      questionnaire was compared with the number of persons with EIB diagnosed by a
      "gold standard" test that consisted of a 7-minute exercise challenge followed by
      serial spirometry. RESULTS: We diagnosed EIB in 9.4% of adolescent athletes. The
      screening history identified persons with symptoms or a previous diagnosis
      suggestive of EIB in 39.5% of the participants, but only 12.9% of these persons
      actually had EIB. Among adolescents with a negative review of symptoms of asthma
      or EIB, 7.8% had EIB. Among adolescents with no previous diagnosis of asthma,
      allergic rhinitis, or EIB, 7.2% had EIB diagnosed by exercise challenge. Persons
      who screened negative on all questions about symptoms or history of asthma, EIB,
      and allergic rhinitis accounted for 45.8% of the adolescents with EIB.
      CONCLUSIONS: EIB occurs frequently in adolescent athletes, and screening by
      physical examination and medical history does not accurately detect it.

PMID- 12219054
TI  - Low bone mass in glycogen storage disease type 1 is associated with reduced
      muscle force and poor metabolic control.
AB  - OBJECTIVE: To study the relation between muscle force, bone mass, and metabolic
      control in patients with glycogen storage disease type (GSD 1). STUDY DESIGN:
      Distal radius bone mass and density were evaluated in 19 patients with GSD 1 (15
      GSD 1a, 4 GSD 1b) by means of peripheral quantitative computed tomography. Grip
      force was quantified with a dynamometer. RESULTS: Height, weight, bone mass, and
      grip force were significantly decreased in the patients with GSD 1a, mainly as
      the result of low values in the poorly controlled subgroup. Boys had lower bone
      mass than girls. Patients with GSD 1b had higher values for bone mineral density
      in the trabecular compartment. In most of the study participants bone mass
      appeared to be adequately adapted to the mechanical requirements imposed by
      muscle contraction. However, 3 patients with GSD 1a had evidence for a low bone
      mass. CONCLUSIONS: In GSD 1, both reduced muscle strength and a direct disease
      effect can contribute to low bone mass. The quality of treatment is crucial to
      prevent disturbances in musculoskeletal development.

PMID- 12219055
TI  - Gains in hip bone mass from high-impact training are maintained: a randomized
      controlled trial in children.
AB  - OBJECTIVES: We previously reported significant gains in hip and spine bone mass
      after 7 months of high-impact training in 89 prepubertal children. Our aim in
      this investigation was to evaluate the bone response to 7 months of "detraining"
      in this cohort of children. STUDY DESIGN: Seventy-four boys and girls (n = 37
      jumpers, n = 37 controls) from the original cohort completed follow-up testing.
      Bone mineral content (BMC; g) and bone area (BA; cm(2)) of the left proximal
      femoral neck and lumbar spine (L(1-4)) were assessed by dual-energy x-ray
      absorptiometry. In addition, anthropometric characteristics, Tanner staging,
      physical activity, and average dietary calcium intake were assessed. RESULTS:
      Over 14 months, jumpers maintained 4% greater femoral neck BMC and 4% greater
      femoral neck BA (P <.05 and P <.01, respectively) than controls. Group
      differences did not persist at the lumbar spine. CONCLUSION: Gains in both BMC
      and BA at the femoral neck from high-impact jumping were retained after an
      equivalent period of detraining. We conclude that this simple exercise may be
      useful in promoting bone growth at the hip and, thus, enhance peak bone mass.

PMID- 12219056
TI  - Relation of sleep state to hypoxemic episodes in ventilated extremely-low-birth
      weight infants.
AB  - OBJECTIVE: To determine whether hypoxemic episodes in ventilated extremely-low
      birth-weight infants correlate with specific behavioral states. STUDY DESIGN:
      Three-hour video-electroencephalography-polysomnography was performed on 13
      ventilated extremely-low-birth-weight infants with mean postconceptional age of
      28.3 weeks. The electroencephalogram was scored for discontinuity. Rapid eye
      movements, body, head, and limb movements were scored from synchronized video.
      Sleep states were defined from electroencephalography, rapid eye movements, and
      movement criteria. Nonparametric statistics were used to test for differences in
      the proportion of time hypoxemic (oxygen saturation </=85%) between behavioral
      states. RESULTS: The proportions of time hypoxemic were 0.6% during quiet sleep,
      4.4% during active sleep, 10.7% during indeterminate sleep, and 16.7% during
      arousal. There was a significant overall difference between the states (P =.004)
      and a significant difference between active sleep and indeterminate sleep in a
      pairwise comparison (P =.001). CONCLUSIONS: Higher proportions of hypoxemia were
      found during indeterminate sleep and arousal compared with active sleep and quiet
      sleep. We speculate that motor activity during sleep disruption could prevent
      effective mechanical delivery of ventilator breaths and contribute to episodes of
      hypoxemia. Our results suggest that strategies promoting uninterrupted sleep
      cycling analogous to the intrauterine state could improve ventilatory stability.

PMID- 12219057
TI  - Minimal ventilation to prevent bronchopulmonary dysplasia in extremely-low-birth
      weight infants.
AB  - OBJECTIVE: To determine whether minimal ventilation decreases death or
      bronchopulmonary dysplasia (BPD). STUDY DESIGN: Infants with birth weight 501 g
      to 1000 g and mechanically ventilated before 12 hours were randomly assigned to
      minimal ventilation (partial pressure of carbon dioxide [PCO(2)] target >52 mm
      Hg) or routine ventilation (PCO(2) target <48 mm Hg) and a tapered dexamethasone
      course or saline placebo for 10 days, using a 2 x 2 factorial design. The primary
      outcome was death or BPD at 36 weeks' postmenstrual age. RESULTS: After
      enrollment of 220 patients, the trial was halted because of unanticipated
      nonrespiratory adverse events related to dexamethasone therapy. The relative risk
      for death or BPD at 36 weeks in the minimal versus routine ventilation groups was
      0.93 (95% CI, 0.77-1.12; P =.43). Ventilator support at 36 weeks was 1% in the
      minimal versus 16% in the routine group (P <.01). Major morbidities and long-term
      outcome were comparable in both treatment groups. CONCLUSIONS: With the sample
      size studied, minimal ventilation did not reduce the incidence of death or BPD.
      The reduced ventilator support at 36 weeks in the minimal ventilation group
      warrants further study of this intervention.

PMID- 12219058
TI  - Low birth weight for gestational age and subsequent male gonadal function.
AB  - OBJECTIVE: To verify whether a reduced birth weight for gestational age was
      associated with a testicular dysfunction in postpubertal boys. STUDY DESIGN: Boys
      born small for gestational age (SGA) (n = 25) were compared to 24 born with an
      appropriate weight. All subjects were postpubertal (mean age 17.5 +/- 1.3 and
      17.6 +/- 2.0 years, respectively). The following clinical and endocrinologic
      variables were evaluated: final height, target height, body mass index,
      testicular volume, follicle-stimulating hormone, luteinizing hormone,
      testosterone, and inhibin B. RESULTS: The SGA group had reduced testicular size
      (16.3 +/- 2.7 mL vs 22.8 +/- 3.2 mL; P <.0001) with a lower testosterone level
      (3.76 +/- 1.35 ng/mL vs 4.77 +/- 1.55 ng/mL; P <.05) and a higher LH value (4.41
      +/- 1.61 IU/L vs 3.44 +/- 1.29 IU/L; P <.05). Among the SGA group, 54% had a mean
      testicular volume >2 SD below the control mean (ie, <16 mL) and in these
      subjects, the inhibin B level was low (143 +/- 46 pg/mL vs 229 +/- 76 pg/mL; P
      <.0001). SGA patients with smaller testes had lower final height relative to
      target height(P <.05 vs patients with larger testes) and for the SGA group,
      inhibin B correlated with testicular size (P <.0001). Positive correlations also
      were found between the reduction of final height relative to target height and
      testicular volume (P <.005) and inhibin B values (P <.05). CONCLUSIONS: SGA
      subjects have pituitary-gonadal axis function that tends toward hypogonadism.
      There is a disruption of the exocrine function in subjects with smaller
      testicular size who failed to show a complete height catch-up growth. This study
      supports a link between low birth weight and lower fertility in adult males.

PMID- 12219060
TI  - Pre-auricular tags and pits in the newborn: the role of renal ultrasonography.
AB  - OBJECTIVE: To determine the role of renal ultrasonography in the evaluation of
      healthy newborn infants with isolated pre-auricular tags and pits. STUDY DESIGN:
      During the 4 years of prospective study, 108 of 17,286 infants were born with
      isolated pre-auricular tags or pits (6.2 per 1000 live births): 92 were assessed
      for urinary tract abnormalities by performing renal ultrasonography at 1 to 3
      months of age. The study group was compared with a control group of 95
      consecutive healthy infants without pre-auricular tags or pits born during the
      same period who underwent renal ultrasonography on the second day of life.
      RESULTS: The study and control groups were comparable in birth weight,
      gestational age, and sex ratio. Renal ultrasonography was abnormal only in 2
      infants with pre-auricular tags (2.2%); both had mild left pyelectasis. The
      prevalence did not differ significantly from that in the control group, in which
      3 infants had mild pyelectasis (3.1%, P = 1.0) and 1 infant had a renal calculus.
      The prevalence of renal abnormalities in infants with isolated pre-auricular tags
      or pits in our study (2.2%) was also comparable to the prevalence in the general
      population (all abnormalities 0.2%-8.1%; significant abnormalities 0.2%-1.4%).
      CONCLUSIONS: We conclude that renal ultrasonography is not indicated in the
      routine evaluation of the newborn infant with isolated pre-auricular tags or
      pits.

PMID- 12219059
TI  - Infection due to extended-spectrum beta-lactamase-producing Salmonella enterica
      subsp. enterica serotype infantis in a neonatal unit.
AB  - OBJECTIVE: To describe the investigation and control of an outbreak of extended
      spectrum beta-lactamase producing Salmonella enterica subsp. enterica serotype
      Infantis in a neonatal unit in Brazil. METHODS: A case-control study for risk
      factors for Salmonella Infantis systemic infection, environmental cultures, and
      evaluation of staffing and overcrowding and an assessment of infection control
      practices were performed. RESULTS: During July 1998 to June 1999, 140 Salmonella
      Infantis culture-positive patients were identified in the neonatal unit. Presence
      of a peripheral intravascular catheter was identified as an independent risk
      factor (odds ratio = 4.98; 95% CI = 1.59-19.31; P =.01) and each 250-g increase
      in birth weight as a protective factor (odds ratio = 0.76; 95% CI = 0.57-0.95; P
      =.03). Hospital stay was significantly longer and costs higher in case patients
      than in control patients. Salmonella Infantis was isolated from multiple
      environmental sources. Neonatal unit personnel were observed to make several
      breaks in infection control practices. The unit was understaffed and overcrowded.
      Prompt case identification, cohorting of patients, enhanced staff hand hygiene,
      and environmental cleaning terminated the outbreak. CONCLUSIONS: Inadequate
      infection control practices, nursery overcrowding, and understaffing can have an
      adverse effect on patient morbidity, mortality rates, and hospital cost.

PMID- 12219061
TI  - The impact of legislation and secular trends on newborn length of stay for
      Medicaid infants in Ohio.
AB  - OBJECTIVES: To examine the impact of state legislation mandating minimum maternal
      and newborn length of stay (LOS). STUDY DESIGN: By using Medicaid claims data
      linked to vital statistics files, LOS, and "short stay" (</=1 day after vaginal
      delivery, </=2 days after cesarean delivery) were determined for 151,464 term
      newborns born to mothers receiving Medicaid in Ohio from July 1, 1991 to June 30,
      1998. Changes in LOS and "short stay" were examined for 4 periods that reflected
      events occurring in Ohio at the time. RESULTS: The proportion of newborns
      discharged after a "short stay" increased dramatically before legislation (7/1/91
      8/31/95) but decreased after the introduction of legislation (9/1/95-6/30/96). In
      the 4 months after passage of the law, but before its effective date (Period
      III), the odds of a "short stay" decreased. This decrease continued in the 20
      months after the law went into effect (Period IV). White, young, married mothers
      without a high school degree or with poor prenatal care and lower birth weight
      infants were more likely to be discharged early. CONCLUSIONS: LOS and "short
      stay" returned to near-1991 levels for Medicaid newborns in Ohio after
      legislative activity.

PMID- 12219062
TI  - Physiologic studies on swaddling: an ancient child care practice, which may
      promote the supine position for infant sleep.
AB  - OBJECTIVE: The calming effects of swaddling may help infants accept back sleeping
      and so reduce the risk of sudden infant death syndrome. We hypothesized that
      swaddling, with minimal leg restraint, would be accepted by postneonatal infants
      with minimal respiratory effects. STUDY DESIGN: Postneonatal infants (n = 37)were
      studied for the introduction of swaddling. Four infants were studied by using
      traditional swaddling techniques. Swaddle tightness was increased in 13 infants,
      simulating traditional swaddles. Respiratory variables-respiratory rate, tidal
      volume, oxygen saturation, heart rate, sigh rate, and "grunting"-were measured.
      RESULTS: Hips were flexed and abducted in the swaddle. The majority of infants
      accepted swaddling while supine, including 78% of infants who slept prone at
      home. Acceptance decreased with increasing age. With increased swaddle pressure,
      respiratory rate increased during quiet sleep (P <.05). In rapid eye movement
      sleep, a slight effect on heart rate was observed (P <.05). Other variables did
      not change. CONCLUSIONS: Older infants including usual prone sleepers generally
      accept a form of swaddling that has minimal respiratory effects. The
      reintroduction of swaddling, without restricting hip movement or chest wall
      excursion, combined with supine sleeping, may promote further sudden infant death
      syndrome reduction.

PMID- 12219063
TI  - Iron status at 9 months of infants with low iron stores at birth.
AB  - OBJECTIVE: To determine the 9-month follow-up iron status of infants born with
      abnormally low serum ferritin concentrations. STUDY DESIGN: Ten infants of >34
      weeks' gestation with cord serum ferritin concentrations <5th percentile at birth
      (<70 microg/L) and 12 control infants with cord serum ferritin concentrations >80
      microg/L had follow-up serum ferritin concentrations measured at 9 +/- 1 month of
      age. The mean follow-up ferritins, incidences of iron deficiency and iron
      deficiency anemia, and growth rates from 0 to 12 months were compared between the
      two groups. RESULTS: At follow-up, the low birth ferritin group had a lower mean
      ferritin than the control group (30 +/- 17 vs 57 +/- 33 microg/L; P =.03), but no
      infant in either group had iron deficiency (serum ferritin <10 microg/L) or iron
      deficiency anemia. Both groups grew equally well, but more rapid growth rates
      were associated with lower follow-up ferritin concentrations only in the low
      birth ferritin group (r = -0.52; P =.05). Both groups were predominantly breast
      fed without iron supplementation before 6 months. CONCLUSIONS: Infants born with
      serum ferritin concentrations <5th percentile continue to have significantly
      lower ferritin concentrations at 9 months of age compared with infants born with
      normal iron status, potentially conferring a greater risk of later onset iron
      deficiency in the second postnatal year.

PMID- 12219064
TI  - Dose response of PEG 3350 for the treatment of childhood fecal impaction.
AB  - OBJECTIVE: To investigate the efficacy and safety of polyethylene glycol (PEG)
      3350 in the treatment of childhood fecal impaction. METHODS: This was a
      prospective, double-blind, parallel, randomized study of 4 doses of PEG 3350;
      0.25 g/kg per day, 0.5 g/kg per day, 1 g/kg per day, 1.5 g/kg per day, given for
      3 days in children with constipation for >3 months and evidence of fecal
      impaction. RESULTS: Forty patients completed the study (27 boys, median age 7.5,
      range 3.3-13.1 years). Disimpaction occurred in 75% of children, with a
      significant difference between the two higher doses and the lower doses (95% vs
      55%, P <.005). All groups had an increased number of bowel movements during the 5
      day study versus baseline, respectively: 6.5 versus 1.1 (P <.005), 8.0 versus 1.3
      (P <.005), 10.9 versus 1.7 (P <.005), and 12.3 versus 1.4 (P <.005). Adverse
      effects included nausea (5%), vomiting (5%), bloating (18%), cramping (5%), and
      diarrhea (13%). Diarrhea and bloating were more prevalent (P <.02) in the higher
      dose than in the lower-dose group. No clinically significant changes in
      electrolytes were noted. CONCLUSIONS: The 3-day administration of PEG 3350 is
      safe and effective in the treatment of childhood fecal impaction at doses of 1
      and 1.5 g/kg per day.

PMID- 12219065
TI  - Hemostatic and inflammatory markers in obese youths: effects of exercise and
      adiposity.
AB  - OBJECTIVES: To determine the relation of hemostatic markers to cardiovascular
      fitness and adiposity and the effect of physical training (PT) on these markers.
      STUDY DESIGN: Seventy-four obese teenagers were randomly assigned to 8 months of
      lifestyle education (LSE), LSE plus moderate-intensity PT, or LSE plus high
      intensity PT. Measures included fibrinogen, plasminogen activator inhibitor-1
      (PAI-1), D-dimer, C-reactive protein (CRP), fitness, percent body fat (%BF), and
      visceral adiposity (VAT). RESULTS: At baseline, fibrinogen and CRP were
      significantly correlated with %BF and VAT (0.27 </= r </= 0.51), and fitness (r =
      -0.39, r = -0.43, respectively); PAI-1 with %BF (r = 0.30) and VAT (r = 0.48); D
      dimer with fitness (r = -0.24). Although PT produced significant changes in
      fitness and adiposity, there were no significant group differences in the
      hemostatic markers. Change in PAI-1 was significantly correlated with its
      baseline value (r = -0.47) and change in %BF (r = 0.38). Changes in D-dimer and
      CRP were significantly correlated with their respective baseline values (r = 
      0.68,r = -0.48, respectively). CONCLUSIONS: Unfavorable levels of fitness and
      adiposity were associated with higher levels of hemostatic markers, putting
      individuals with this profile at greater risk for future cardiovascular disease.
      No evidence was provided that 8 months of PT had a direct influence on these
      markers in obese youths.

PMID- 12219066
TI  - Joint hypermobility is more common in children with chronic fatigue syndrome than
      in healthy controls.
AB  - OBJECTIVE: To determine whether children with chronic fatigue syndrome (CFS) have
      a higher prevalence of joint hypermobility than gender-matched controls. STUDY
      DESIGN: Matched case-control study comparing the Beighton joint hypermobility
      scores in 58 consecutive children with CFS (incident cases) with 58 otherwise
      healthy controls referred to a dermatology clinic for evaluation of common skin
      problems. A second group of 58 patients previously diagnosed with CFS (prevalent
      cases) was matched by gender to the incident cases to evaluate temporal changes
      in referral patterns. RESULTS: Of the 58 patients in each group, 71% were female.
      The median Beighton scores were higher in incident CFS cases than in healthy
      controls (4 vs 1, P <.001). More incident CFS cases had Beighton scores >/=4
      (consistent with joint hypermobility), 60% versus 24%, P <.0001. Incident and
      prevalent CFS cases had similar Beighton scores. The odds ratio for hypermobility
      in all patients with CFS versus healthy controls was 3.5 (P <.001; 95% CI, 1.6
      7.5). CONCLUSIONS: Joint hypermobility is more common in patients with CFS than
      in otherwise healthy children with common skin disorders. The etiologic
      significance of the observed association remains to be defined.

PMID- 12219067
TI  - The incidence and characteristics of neonatal irreversible lung dysplasia.
AB  - A 3-year retrospective study of 173 neonates treated with extracorporeal membrane
      oxygenation in the United Kingdom identified 9 cases of irreversible lung
      dysplasia, including alveolar capillary dysplasia (n = 5), surfactant protein B
      deficiency (n = 1), pulmonary hypoplasia (n = 1), pulmonary lymphangiectasis (n =
      1), and combined lymphangiectasis and hypoplasia (n = 1).

PMID- 12219068
TI  - Hyperhomocysteinemia as risk factor for ischemic and hemorrhagic stroke in
      newborn infants.
AB  - We studied the association between plasma total homocysteine concentrations and
      the occurrence of stroke in newborn infants (n = 24). Newborn infants with stroke
      had significantly higher mean total homocysteine concentrations compared with 94
      healthy newborn infants (9.3 vs 7.4 micromol/L). The odds ratio for neonatal
      stroke was 3.95 (95" CI 1.53-10.16) at the 80" cutoff level.

PMID- 12219069
TI  - HLA in Egyptian children with biliary atresia.
AB  - We studied the human leukocytes antigens in 18 Egyptian children with biliary
      atresia (BA) without extrahepatic congenital malformations. There was a
      significant increased frequency of both B8 and DR3 (83.3% and 94.4% in patients
      with BA compared with 6.5% and 14.9% in the general population, respectively).
      Ten patients had the B8/DR3 haplotype. Our results support the hypothesis that
      genetic factors may play a role in susceptibility to BA.

PMID- 12219070
TI  - Brain 18-FDG PET scan in central nervous system langerhans cell histiocytosis.
AB  - We used positron emission tomography (PET) to characterize cerebral metabolism in
      7 patients (serial examinations in 2 patients) with central nervous system
      disease in Langerhans cell histiocytosis (CNS-LCH) who had neuroendocrine
      abnormalities (n = 7), neuropsychiatric disabilities (n = 3), and CNS
      degenerative disease (n = 1). The PET scan alterations occurred at localizations
      with known CNS-LCH disease. The PET scans revealed areas where the metabolism and
      function were altered in 6 of the 7 patients studied, with either an increased or
      a decreased metabolism (uptake of glucose). Serial examinations may indicate
      alterations in the degree of ongoing disease activity, but further studies on
      functional imaging are desired. The additional information of PET compared with
      MRI is the ability to detect alterations in CNS metabolic activity in certain
      patients with CNS-LCH. PET may also provide a tool for longitudinal follow-up of
      therapeutic measures in selected patients.

PMID- 12219071
TI  - Central precocious puberty in girls with Williams syndrome.
AB  - We report an estimated prevalence of precocious puberty of 1 in 5 to 6 girls with
      Williams syndrome (18.3%). Mean menarcheal age of 86 girls with Williams syndrome
      was 11.5 +/- 1.7 (+/-SD) years. Distribution of menarcheal age was significantly
      different from that in normal girls (12.9 +/- 1.1 years; n = 759).

PMID- 12219072
TI  - Multifocal desmoplastic astrocytoma, frontal lobe dysplasia, and simian crease.

PMID- 12219073
TI  - Microcephaly and fetal alcohol syndrome.

PMID- 12219074
TI  - Diabetes mellitus: Type 1 or type 2? The accelerator hypothesis.

PMID- 12219075
TI  - A DNA prism for high-speed continuous fractionation of large DNA molecules.
AB  - The analysis and fractionation of large DNA molecules plays a key role in many
      genome projects. The standard method, pulsed-field gel electrophoresis (PFGE), is
      slow, with running times ranging from 10 hours to more than 200 hours. In this
      report, we describe a thumbnail-sized device that sorts large DNA fragments (61
      209 kilobases (kb)) in 15 seconds, with a resolution of approximately 13%. An
      array of micron-scale posts serves as the sieving matrix, and integrated
      microfluidic channels spatially shape the electric fields over the matrix.
      Asymmetric pulsed fields are applied for continuous-flow operation, which sorts
      DNA molecules in different directions according to their molecular masses, much
      as a prism deflects light of different wavelengths at different angles. We
      demonstrate the robustness of the device by using it to separate large DNA
      inserts prepared from bacterial artificial chromosomes, a widely used DNA source
      for most genomics projects.

PMID- 12219076
TI  - A light-switchable gene promoter system.
AB  - Regulatable transgene systems providing easily controlled, conditional induction
      or repression of expression are indispensable tools in biomedical and
      agricultural research and biotechnology. Several such systems have been developed
      for eukaryotes. Most of these rely on the administration of either exogenous
      chemicals or heat shock. Despite the general success of many of these systems,
      the potential for problems, such as toxic, unintended, or pleiotropic effects of
      the inducing chemical or treatment, can impose limitations on their use. We have
      developed a promoter system that can be induced, rapidly and reversibly, by short
      pulses of light. This system is based on the known red light-induced binding of
      the plant photoreceptor phytochrome to the protein PIF3 and the reversal of this
      binding by far-red light. We show here that yeast cells expressing two chimeric
      proteins, a phytochrome-GAL4-DNA-binding-domain fusion and a PIF3-GAL4-activation
      domain fusion, are induced by red light to express selectable or "scorable"
      marker genes containing promoters with a GAL4 DNA-binding site, and that this
      induction is rapidly abrogated by subsequent far-red light. We further show that
      the extent of induction can be controlled precisely by titration of the number of
      photons delivered to the cells by the light pulse. Thus, this system has the
      potential to provide rapid, noninvasive, switchable control of the expression of
      a desired gene to a preselected level in any suitable cell by simple exposure to
      a light signal.

PMID- 12219077
TI  - Oligosaccharide microarrays for high-throughput detection and specificity
      assignments of carbohydrate-protein interactions.
AB  - We describe microarrays of oligosaccharides as neoglycolipids and their robust
      display on nitrocellulose. The arrays are obtained from glycoproteins,
      glycolipids, proteoglycans, polysaccharides, whole organs, or from chemically
      synthesized oligosaccharides. We show that carbohydrate-recognizing proteins
      single out their ligands not only in arrays of homogeneous oligosaccharides but
      also in arrays of heterogeneous oligosaccharides. Initial applications have
      revealed new findings, including: (i) among O-glycans in brain, a relative
      abundance of the Lewis(x) sequence based on N-acetyllactosamine recognized by
      anti-L5, and a paucity of the Lewis(x) sequence based on poly-N-acetyllactosamine
      recognized by anti-SSEA-1; (ii) insights into chondroitin sulfate
      oligosaccharides recognized by an antiserum and an antibody (CS-56) to
      chondroitin sulfates; and (iii) binding of the cytokine interferon-gamma (IFN
      gamma) and the chemokine RANTES to sulfated sequences such as HNK-1, sulfo
      Lewis(x), and sulfo-Lewis(a), in addition to glycosaminoglycans. The approach
      opens the way for discovering new carbohydrate-recognizing proteins in the
      proteome and for mapping the repertoire of carbohydrate recognition structures in
      the glycome.

PMID- 12219078
TI  - Nucleic acid evolution and minimization by nonhomologous random recombination.
AB  - We have developed a simple method for exploring nucleic acid sequence space by
      nonhomologous random recombination (NRR) that enables DNA fragments to randomly
      recombine in a length-controlled manner without the need for sequence homology.
      We compared the results of using NRR and error-prone PCR to evolve DNA aptamers
      that bind streptavidin. Starting with two parental sequences of modest avidin
      affinity, evolution using NRR resulted in aptamers with 15- to 20-fold higher
      affinity than the highest-affinity aptamers evolved using error-prone PCR, and 27
      or 46-fold higher affinities than parental sequences derived using systematic
      evolution of ligands by exponential enrichment (SELEX). NRR also facilitates the
      identification of functional regions within evolved sequences. Inspection of a
      small number of NRR-evolved clones identified a 40-base DNA sequence, present in
      multiple copies in each clone, that binds streptavidin. Our findings suggest that
      NRR may enhance the effectiveness of nucleic acid evolution and the ease of
      identifying structure-activity relationships among evolved sequences.

PMID- 12219079
TI  - Efficient gene targeting by homologous recombination in rice.
AB  - Modification of genes through homologous recombination, termed gene targeting, is
      the most direct method to characterize gene function. In higher plants, however,
      the method is far from a common practice. Here we describe an efficient and
      reproducible procedure with a strong positive/negative selection for gene
      targeting in rice, which feeds more than half of the world's population and is an
      important model plant. About 1% of selected calli and their regenerated fertile
      plants were heterozygous at the targeted locus, and only one copy of the
      selective marker used was found at the targeted site in their genomes. The
      procedure's applicability to other genes will make it feasible to obtain various
      gene-targeted lines of rice.

PMID- 12219080
TI  - Minor proteins, mobile arms and membrane-capsid interactions in the bacteriophage
      PRD1 capsid.
AB  - Bacteriophage PRD1 shares many structural and functional similarities with
      adenovirus. A major difference is the PRD1 internal membrane, which acts in
      concert with vertex proteins to translocate the phage genome into the host.
      Multiresolution models of the PRD1 capsid, together with genetic analyses,
      provide fine details of the molecular interactions associated with particle
      stability and membrane dynamics. The N- and C-termini of the major coat protein
      (P3), which are required for capsid assembly, act as conformational switches
      bridging capsid to membrane and linking P3 trimers. Electrostatic P3-membrane
      interactions increase virion stability upon DNA packaging. Newly revealed
      proteins suggest how the metastable vertex works and how the capsid edges are
      stabilized.

PMID- 12219081
TI  - Arrangement of subunits and ordering of beta-strands in an amyloid sheet.
AB  - Amyloid fibrils are associated with several disease states, but their structures
      have yet to be fully defined. Here we use site-directed spin labeling to explain
      some of the specific interactions that are formed between subunits when the
      protein transthyretin (TTR) assembles into amyloid fibrils, which are associated
      with both spontaneous and familial amyloid diseases in humans. The results
      suggest that fibrils are formed when a major conformational change displaces the
      terminal beta-strand from the edge of a beta-sheet in the native structure,
      exposing the penultimate strand. The newly exposed strand then allows a novel
      beta-sheet interaction to form between the TTR subunits. This interaction and
      another previously identified subunit association lead to a plausible model for
      the specific sequence of beta-strands in one of the indefinitely repeating beta
      sheets of TTR amyloid, which is formed by a head-to-head, tail-to-tail
      arrangement of subunits.

PMID- 12219082
TI  - Conversion of a transmembrane to a water-soluble protein complex by a single
      point mutation.
AB  - Proteins exist in one of two generally incompatible states: either membrane
      associated or soluble. Pore-forming proteins are exceptional because they are
      synthesized as a water-soluble molecule but end up being located in the membrane 
      - that is, they are nonconstitutive membrane proteins. Here we report the
      pronounced effect of the single point mutation Y221G of the pore-forming toxin
      aerolysin. This mutation blocks the hemolytic activity of the toxin but does not
      affect its initial structure, its ability to bind to cell-surface receptors or
      its capacity to form heptamers, which constitute the channel-forming unit. The
      overall structure of the Y221G protein as analyzed by cryo-negative staining EM
      and three-dimensional reconstruction is remarkably similar to that of the wild
      type heptamer. The mutant protein forms a mushroom-shaped complex whose stem
      domain is thought to be within the membrane in the wild type toxin. In contrast
      to the wild type heptamer, which is a hydrophobic complex, the Y221G heptamer is
      fully hydrophilic. This point mutation has, therefore, converted a normally
      membrane-embedded toxin into a soluble complex.

PMID- 12219083
TI  - Crystal structure of the intein homing endonuclease PI-SceI bound to its
      recognition sequence.
AB  - The first X-ray structures of an intein-DNA complex, that of the two-domain
      homing endonuclease PI-SceI bound to its 36-base pair DNA substrate, have been
      determined in the presence and absence of Ca(2+). The DNA shows an asymmetric
      bending pattern, with a major 50 degree bend in the endonuclease domain and a
      minor 22 degree bend in the splicing domain region. Distortions of the DNA bound
      to the endonuclease domain cause the insertion of the two cleavage sites in the
      catalytic center. DNA binding induces changes in the protein conformation. The
      two overlapping non-identical active sites in the endonucleolytic center contain
      two Ca(+2) ions that coordinate to the catalytic Asp residues. Structure analysis
      indicates that the top strand may be cleaved first.

PMID- 12219084
TI  - Epstein-Barr virus-associated Burkitt lymphomagenesis selects for downregulation
      of the nuclear antigen EBNA2.
AB  - Epstein-Barr virus (EBV) is etiologically linked to endemic Burkitt lymphoma
      (BL), but its contribution to lymphomagenesis, versus that of the chromosomal
      translocation leading to c-myc gene deregulation, remains unclear. The virus's
      growth-transforming (Latency III) program of gene expression is extinguished in
      tumor cells, and only a single viral protein, the EBV nuclear antigen (EBNA)1, is
      expressed via the alternative Latency I program. It is not known if BL arises
      from a B-cell subset in which EBV naturally adopts a Latency I infection or if a
      clone with limited antigen expression has been selected from an EBV-transformed
      Latency III progenitor pool. Here we identify a subset of BL tumors in which the
      Latency III-associated EBNA promoter Wp is active and most EBNAs are expressed,
      but where a gene deletion has specifically abrogated the expression of EBNA2.
      This implies that BL can be selected from a Latency III progenitor and that the
      principal selection pressure is for downregulation of the c-Myc antagonist EBNA2.

PMID- 12219085
TI  - Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated
      trefoil gene activation in gp130 mutant mice.
AB  - The intracellular signaling mechanisms that specify tissue-specific responses to
      the interleukin-6 (IL-6) family of cytokines are not well understood. Here, we
      evaluated the functions of the two major signaling pathways, the signal
      transducers and activators of transcription 1 and 3 (STAT1/3) and the Src
      homology tyrosine phosphatase 2 (SHP2)-Ras-ERK, emanating from the common signal
      transducer, gp130, in the gastrointestinal tract. Gp130(757F) mice, with a 'knock
      in' mutation abrogating SHP2-Ras-ERK signaling, developed gastric adenomas by
      three months of age. In contrast, mice harboring the reciprocal mutation ablating
      STAT1/3 signaling (gp130(Delta STAT)), or deficient in IL-6-mediated gp130
      signaling (IL-6(-/-) mice), showed impaired colonic mucosal wound healing. These
      gastrointestinal phenotypes are highly similar to the phenotypes exhibited by
      mice deficient in trefoil factor 1 (pS2/TFF1) and intestinal trefoil factor
      (ITF)/TFF3, respectively, and corresponded closely with the capacity of the two
      pathways to stimulate transcription of the genes encoding pS2/TFF1 and ITF/TFF3.
      We propose a model whereby mucosal wound healing depends solely on activation of
      STAT1/3, whereas gastric hyperplasia ensues when the coordinated activation of
      the STAT1/3 and SHP2-Ras-ERK pathways is disrupted.

PMID- 12219086
TI  - A pantothenate auxotroph of Mycobacterium tuberculosis is highly attenuated and
      protects mice against tuberculosis.
AB  - With the advent of HIV and the widespread emergence of drug-resistant strains of
      Mycobacterium tuberculosis, newer control strategies in the form of a better
      vaccine could decrease the global incidence of tuberculosis. A desirable trait in
      an effective live attenuated vaccine strain is an ability to persist within the
      host in a limited fashion in order to produce important protective antigens in
      vivo. Attenuated M. tuberculosis vaccine candidates have been constructed by
      deleting genes required for growth in mice. These candidate vaccines did not
      elicit adequate protective immunity in animal models, due to their inability to
      persist sufficiently long within the host tissues. Here we report that an
      auxotrophic mutant of M. tuberculosis defective in the de novo biosynthesis of
      pantothenic acid (vitamin B5) is highly attenuated in immunocompromised SCID mice
      and in immunocompetent BALB/c mice. SCID mice infected with the pantothenate
      auxotroph survived significantly longer (250 days) than mice infected with either
      bacille Calmette-Guerin (BCG) vaccine or virulent M. tuberculosis (77 and 35
      days, respectively). Subcutaneous immunization with this auxotroph conferred
      protection in C57BL/6J mice against an aerosol challenge with virulent M.
      tuberculosis, which was comparable with that afforded by BCG vaccination. Our
      findings highlight the importance of de novo pantothenate biosynthesis in
      limiting the intracellular survival and pathogenesis of M. tuberculosis without
      reducing its immunogenicity in vaccinated mice.

PMID- 12219087
TI  - Regulation of insulin action and pancreatic beta-cell function by mutated alleles
      of the gene encoding forkhead transcription factor Foxo1.
AB  - Type 2 diabetes results from impaired action and secretion of insulin. It is not
      known whether the two defects share a common pathogenesis. We show that
      haploinsufficiency of the Foxo1 gene, encoding a forkhead transcription factor
      (forkhead box transcription factor O1), restores insulin sensitivity and rescues
      the diabetic phenotype in insulin-resistant mice by reducing hepatic expression
      of glucogenetic genes and increasing adipocyte expression of insulin-sensitizing
      genes. Conversely, a gain-of-function Foxo1 mutation targeted to liver and
      pancreatic beta-cells results in diabetes arising from a combination of increased
      hepatic glucose production and impaired beta-cell compensation due to decreased
      Pdx1 expression. These data indicate that Foxo1 is a negative regulator of
      insulin sensitivity in liver, adipocytes and pancreatic beta-cells. Impaired
      insulin signaling to Foxo1 provides a unifying mechanism for the common metabolic
      abnormalities of type 2 diabetes.NOTE: In the AOP version of this article, the
      name of the fourth author was misspelled as W K Cavanee rather than the correct
      spelling: W K Cavenee. This has been corrected in the full-text online version of
      the article. The name will appear correctly in the print version.

PMID- 12219088
TI  - Variation in gene expression within and among natural populations.
AB  - Evolution may depend more strongly on variation in gene expression than on
      differences between variant forms of proteins. Regions of DNA that affect gene
      expression are highly variable, containing 0.6% polymorphic sites. These
      naturally occurring polymorphic nucleotides can alter in vivo transcription
      rates. Thus, one might expect substantial variation in gene expression between
      individuals. But the natural variation in mRNA expression for a large number of
      genes has not been measured. Here we report microarray studies addressing the
      variation in gene expression within and between natural populations of teleost
      fish of the genus Fundulus. We observed statistically significant differences in
      expression between individuals within the same population for approximately 18%
      of 907 genes. Expression typically differed by a factor of 1.5, and often more
      than 2.0. Differences between populations increased the variation. Much of the
      variation between populations was a positive function of the variation within
      populations and thus is most parsimoniously described as random. Some genes
      showed unexpected patterns of expression--changes unrelated to evolutionary
      distance. These data suggest that substantial natural variation exists in gene
      expression and that this quantitative variation is important in evolution.

PMID- 12219089
TI  - Evidence for two apoptotic pathways in light-induced retinal degeneration.
AB  - Excessive phototransduction signaling is thought to be involved in light-induced
      and inherited retinal degeneration. Using knockout mice with defects in rhodopsin
      shut-off and transducin signaling, we show that two different pathways of
      photoreceptor-cell apoptosis are induced by light. Bright light induces apoptosis
      that is independent of transducin and accompanied by induction of the
      transcription factor AP-1. By contrast, low light induces an apoptotic pathway
      that requires transducin. We also provide evidence that additional genetic
      factors regulate sensitivity to light-induced damage. Our use of defined mouse
      mutants resolves some of the complexity underlying the mechanisms that regulate
      susceptibility to retinal degeneration.

PMID- 12219091
TI  - Genome sequence of the endocellular obligate symbiont of tsetse flies,
      Wigglesworthia glossinidia.
AB  - Many insects that rely on a single food source throughout their developmental
      cycle harbor beneficial microbes that provide nutrients absent from their
      restricted diet. Tsetse flies, the vectors of African trypanosomes, feed
      exclusively on blood and rely on one such intracellular microbe for nutritional
      provisioning and fecundity. As a result of co-evolution with hosts over millions
      of years, these mutualists have lost the ability to survive outside the sheltered
      environment of their host insect cells. We present the complete annotated genome
      of Wigglesworthia glossinidia brevipalpis, which is composed of one chromosome of
      697,724 base pairs (bp) and one small plasmid, called pWig1, of 5,200 bp. Genes
      involved in the biosynthesis of vitamin metabolites, apparently essential for
      host nutrition and fecundity, have been retained. Unexpectedly, this obligate's
      genome bears hallmarks of both parasitic and free-living microbes, and the gene
      encoding the important regulatory protein DnaA is absent.

PMID- 12219090
TI  - Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes.
AB  - Interferon regulatory factor 6 (IRF6) belongs to a family of nine transcription
      factors that share a highly conserved helix-turn-helix DNA-binding domain and a
      less conserved protein-binding domain. Most IRFs regulate the expression of
      interferon-alpha and -beta after viral infection, but the function of IRF6 is
      unknown. The gene encoding IRF6 is located in the critical region for the Van der
      Woude syndrome (VWS; OMIM 119300) locus at chromosome 1q32-q41 (refs 2,3). The
      disorder is an autosomal dominant form of cleft lip and palate with lip pits, and
      is the most common syndromic form of cleft lip or palate. Popliteal pterygium
      syndrome (PPS; OMIM 119500) is a disorder with a similar orofacial phenotype that
      also includes skin and genital anomalies. Phenotypic overlap and linkage data
      suggest that these two disorders are allelic. We found a nonsense mutation in
      IRF6 in the affected twin of a pair of monozygotic twins who were discordant for
      VWS. Subsequently, we identified mutations in IRF6 in 45 additional unrelated
      families affected with VWS and distinct mutations in 13 families affected with
      PPS. Expression analyses showed high levels of Irf6 mRNA along the medial edge of
      the fusing palate, tooth buds, hair follicles, genitalia and skin. Our
      observations demonstrate that haploinsufficiency of IRF6 disrupts orofacial
      development and are consistent with dominant-negative mutations disturbing
      development of the skin and genitalia.

PMID- 12219092
TI  - What constitutes an efficient reference frame for vision?
AB  - Vision requires a reference frame. To what extent does this reference frame
      depend on the structure of the visual input, rather than just on retinal
      landmarks? This question is particularly relevant to the perception of dynamic
      scenes, when keeping track of external motion relative to the retina is
      difficult. We tested human subjects' ability to discriminate the motion and
      temporal coherence of changing elements that were embedded in global patterns and
      whose perceptual organization was manipulated in a way that caused only minor
      changes to the retinal image. Coherence discriminations were always better when
      local elements were perceived to be organized as a global moving form than when
      they were perceived to be unorganized, individually moving entities. Our results
      indicate that perceived form influences the neural representation of its
      component features, and from this, we propose a new method for studying
      perceptual organization.

PMID- 12219093
TI  - Greater plasticity in lower-level than higher-level visual motion processing in a
      passive perceptual learning task.
AB  - Simple exposure is sufficient to sensitize the human visual system to a
      particular direction of motion, but the underlying mechanisms of this process are
      unclear. Here, in a passive perceptual learning task, we found that exposure to
      task-irrelevant motion improved sensitivity to the local motion directions within
      the stimulus, which are processed at low levels of the visual system. In
      contrast, task-irrelevant motion had no effect on sensitivity to the global
      motion direction, which is processed at higher levels. The improvement persisted
      for at least several months. These results indicate that when attentional
      influence is limited, lower-level motion processing is more receptive to long
      term modification than higher-level motion processing in the visual cortex.

PMID- 12219094
TI  - Auditory midbrain neurons that count.
AB  - Many acoustic communication signals, including human speech and music, consist of
      a precise temporal arrangement of discrete elements, but it is unclear whether
      this precise temporal patterning is required to activate the sensory neurons that
      mediate signal recognition. In a variety of systems, neurons respond selectively
      when two or more sound elements are presented in a particular temporal order and
      the precise relative timing of these elements is particularly important for
      'delay-tuned' neurons, including 'tracking' types, in bats. Here we show that one
      class of auditory neurons in the midbrain of anurans (frogs and toads) responds
      only to a series of specific interpulse intervals (IPIs); in the most selective
      cases, a single interval that is slightly longer or shorter than the requisite
      interval can reset this interval-counting process.

PMID- 12219095
TI  - Enhanced tactile spatial acuity and cortical processing during acute hand
      deafferentation.
AB  - Acute deafferentation of a limb results in bilateral cortical reorganization, but
      the behavioral consequences of this phenomenon are unknown. Here we found rapid
      improvements in tactile spatial acuity and changes in cortical processing for the
      left hand during cutaneous anesthesia of the right hand. The site-specific
      improvement in tactile spatial acuity may represent a behavioral compensatory
      gain.

PMID- 12219096
TI  - A transmembrane motif governs the surface trafficking of nicotinic acetylcholine
      receptors.
AB  - Surface expression of the nicotinic acetylcholine receptor (AChR) requires the
      assembly of multiple subunits in the endoplasmic reticulum (ER). Little is known,
      however, about the mechanism by which assembled receptor pentamers are
      transported to the cell membrane while unassembled subunits are retained in the
      ER. Here we report that a motif conserved in the transmembrane domain of AChR
      subunits is critically involved in this process. In COS cells, mutation within
      this signal allowed surface expression of unassembled subunits. Conversely,
      insertion of the sequence to unrelated proteins that are normally transported to
      the surface resulted in ER retention. The signal is buried in AChR pentamers, but
      is exposed on unassembled subunits in the ER, where it promotes protein
      degradation. We therefore conclude that this signal ensures surface trafficking
      of only functional AChRs.

PMID- 12219097
TI  - Transient neural activity in human parietal cortex during spatial attention
      shifts.
AB  - Observers viewing a complex visual scene selectively attend to relevant locations
      or objects and ignore irrelevant ones. Selective attention to an object enhances
      its neural representation in extrastriate cortex, compared with those of
      unattended objects, via top-down attentional control signals. The posterior
      parietal cortex is centrally involved in this control of spatial attention. We
      examined brain activity during attention shifts using rapid, event-related fMRI
      of human observers as they covertly shifted attention between two peripheral
      spatial locations. Activation in extrastriate cortex increased after a shift of
      attention to the contralateral visual field and remained high during sustained
      contralateral attention. The time course of activity was substantially different
      in posterior parietal cortex, where transient increases in activation accompanied
      shifts of attention in either direction. This result suggests that activation of
      the parietal cortex is associated with a discrete signal to shift spatial
      attention, and is not the source of a signal to continuously maintain the current
      attentive state.

PMID- 12219098
TI  - [PROPHYLACTIC ANTIBIOTICS IN GASTROINTESTINAL ENDOSCOPY]

PMID- 12219099
TI  - [GASTROINTESTINAL BLEEDING IN PATIENTS ADMITTED TO THECAYETADNO HEREDIA PUBLIC
      HOSPITAL]
AB  - A prospective study was performed to evaluate the epidemiological
      characteristics, clinical outcome and to determine the cause of bleeding in
      patients admitted to the Cayetano Heredia National Hospital with the diagnosis of
      gastrointestinal bleeding. Between August 1994 and May 1995, 100 patients were
      admitted, 86 patients with upper gastrointestinal bleeding and 14 with lower
      gastrointestinal bleeding. The mean age for the former was 45,25 years and the
      male/female ratio was 3.5/1. The main complaints were tarry stools and
      haematemesis in 56,9% and 26,7% only with melena. A history of non steroidal
      antiinflamatory drugs intake within 48 hours before the bleeding episode was
      obtained in 19,7% and alcohol ingestion was observed in 19,7%. In 36% of the
      patients a history of a previous episode of bleeding was obtained. The major
      causes of bleeding were duodenal ulcer in 38,3%, acute lesions of the gastric
      mucosa in 20,9%, gastric ulcer in 11,6% and esophageal varices in 5,8%, Mallory
      Weiss syndrome in 4,6%, gastric carcinoma in 2,3%, prolapse gastropaty 2,3%,
      esophagitis in 2,3%, esophageal ulcer 1,1 %, duodenitis 1,1%, arteriovenus
      malformations in 1,1%. The etiology of the hemorrhage could not be established in
      8% of cases. The diagnostic rate of endoscopy was 91,7%.In 66% of the patients
      the endoscopy was carried out within the 24 hours of admission 20,9% of the
      patients had other potential bleeding lesions 9,1% of the patients had a new
      episode of bleeding during hospitalization and surgery was needed in 11,6%.
      Injectotheraphy was done in 7 (8,13%) patients (4 for variceal 2 for duodenal and
      1 for gastric bleeding ) The overall mortality was 3,4% Fourteen patients with
      lower gastrointestinal bleeding were evaluated. The mean age was 53,14 years and
      the male/female ratio was 1.6/1. The main complaint was hematochezia. The major
      causes of bleeding were hemorrhoidal disease in 64,2% and rectal cancer in
      14,28%.

PMID- 12219100
TI  - [HORIZONTAL TRANSMISSION OF HBV INFECTION IN MIGRANTSFROM A HYPERENDEMIC AREA TO
      THEIR CONTACTS IN A LOW ENDEMICITY AREA IN PERU]
AB  - Migration of inhabitants from high endemicity to low endemicity areas, where the
      majority of population is susceptible, implies a risk of transmission. This
      factor suggested the study of the presence of HBV infection on migrants from
      Huanta and in their host communities in Lima.MATERIAL AND METHODS: Forty families
      from a human settlement in the District of San Juan de Lurigancho, Lima, were
      chosen at random. This sample included migrant families and people who had born
      in Lima.The members of these families were subjected to a survey to obtain
      demographic data and possible risk factor for HBV infection, and venous blood
      sample was obtained to determine HBV serological markers by ELIZA
      techniques.RESULTS: A total of 215 people were evaluated, 130 (60,5%) were
      female, and 85 (39,5%) were male. There were 9 (4,2%) HbsAg carriers; 4 (1,9%) of
      them were born in Huanta; the other 5 (2,3%) were born in Lima, and had never
      been to Huanta. They were under 20 years of age. No significant association was
      found between the presence of HbsAg and the use of injectables, blood
      transfusions, tatoos, previous surgery, dental extractions or sexual
      relations.CONCLUSION: The presence of HbsAg carrier on people born in Lima, with
      no "classical" risk factor for HBV infection, could be associated with carriers
      migrating from a hyperendemic HBV area, suggesting a mechanism of horizontal
      transmission.

PMID- 12219101
TI  - [OPERABILITY AND RESECTABILITY OF GASTRIC CANCER:ANALYSIS OF 2280 CASES IN 15
      YEARS]
AB  - OBJECTIVES: To determine which are the operability and resectability tendencies
      of gastric cancer in Peru.BACKGROUND: In Peru, gastric cancer is the first cause
      of death in men and the third one in women. Most of the patients with gastric
      cancer receive treatment al the Instituto Nacional de Enfermedades Neoplasicas of
      Lima (INEN).PATIENTS AND METHODS: Every patient with untreated histologically
      verified gastric adenocarcinoma, who was admitted to the INEN between January
      1980, and December 1994, was included.We determined the actual trends of
      operability and resectability. These rates were calculated and compared with
      rates of the 1952-1977 period.The 1980-1994 period was divided in lustrums to
      evaluate a more complete preoperative staging act upon operability and
      resectability.The causes of inoperability and irresectability were also
      determined.RESULTS: Between 1980 and 1994 a total of 2280 new gastric cancer
      patients were admitted to the INEN. The operability and resectability rates of
      the 1980-1994 period (56,8% and 58,5% respectively) differ significantly from
      rates of the 1952-1977 period (43,8% and 49,2% respectively). A more complete
      preoperative staging produces a decrease of operability and an increase of
      resectability.The main causes of inoperability were poor physical condition
      associated to a locally advanced tumor 34%, and peritoneal metastases 26%. The
      main causes of irresectability were peritoneal metastases 50,3%, and invasion to
      adjacent organs 26,7%.CONCLUSIONS: Even when there is an increase of operability
      and resectability rates, gastric cancer is still diagnosed al a late stage in
      Peru. It is vital to stage pathology precisely to avoid unnecessary laparotomies.

PMID- 12219102
TI  - [GASTRODUODENAL ULCER IN PEDIATRICS]
AB  - 476 endoscopic reports of 435 children under 15 years old of both sexes were
      reviewed to determine the morbility of gastroduodenal peptic ulcer. Endoscopy was
      performed because they had symptoms referred to the upper gastrointestinal tract
      between December 1989 and December 1994. Gastroduodenal ulcer was diagnosed in
      forty five children (10,3%). Primary ulcer was diagnosed in twenty four patients
      (55%) and secondary ulcers in twenty one (45%), being the administration of
      ulcerogenic drugs the main factor involved. Primary ulcer was more frequently
      diagnosed in older children and teenagers and localized mainly in the duodenum.
      Male sex was predominant in both types of ulcers. 42% of children with primary
      ulcers had familiar ocurrence of ulcer disease. Thirty three patients (73%) had
      complications, being gastrointestinal bleeding the most frequent. Ulcer disease
      is not rare in children and must be suspected in patients with recurrent
      abdominal pain.

PMID- 12219103
TI  - [FACTORS RELATED TO MORTALITY IN NECROTIZINGENTEROCOLITIS(NEC) IN NEONATES AND
      OLDER INFANTS]
AB  - In order to determine the factors related to mortality in Necrotizing
      enterocolitis (NEC), medical records of neonates and older infants diagnosed of
      NEC in the Instituto de Salud del Nino between 1984 and 1993 were retrospectively
      reviewed. Only the cases with a reliable roentgenologic, surgical or pathologic
      diagnosis were included. Sixty cases (46 infants and 14 neonates) were found,
      with a higher incidence in males (37 males vs 23 females). Twenty six cases
      required surgical treatment. Overall mortality was 77%, with no significant
      differences between neonates and infants, nor between those who were operated or
      not. Moderate or severe malnutrition, diarrhea as an early clinical
      manifestations, bronchopneumonia, shock and poor nutricional management were
      found as factors related to mortality.

PMID- 12219104
TI  - [PREVALENCE OF ANTI-HCV IN HOSPITALIZED CHILDREN]
AB  - In the last years, one of the causative agents of post-transfusion non A non B
      hepatitis has been identified as hepatitis virus C(HCV). In order to determine
      the HCV prevalence in a pediatric population, an anti-HCV determination through
      Cuban manufactured Microelisa system was done to 500 hospitalized children under
      14 years old, of both sex, for six months. The samples repeatedly reactive were
      considered positive, the risk factors for this infection were evaluated and the
      Relative Risk was estimated. Seven patients (1,4% of the sample) were HCV
      positive, and underwent clinical, biochemical, immunological, echographic,
      laparoscopic and histological examinations to determine the hepatic damages
      associated to the presence of this virus. The Relative Risk for HCV is 4,5 times
      more for those with previous surgical operation, 3,9 for those who have had more
      than four previous hospitalizations and, of 2,6 and 1,9 for those with previous
      transfusion and treatment with vaccine, respectively. The predominant
      histological lesion reported was a minimum damage of the liver cells. It is
      important to screen for HCV in blood banks and to study other possible routes of
      transmission. We recommend the follow up of these patients for the possibility of
      cronical sequela.

PMID- 12219105
TI  - [INTESTINAL TRANSPLANTATION IN PEDIATRICS]
AB  - Intestinal Transplantation used to be an utopia in Medicine, and this was mainly
      due to the factor that the surgical technique was not the best at the beginning.
      When this was perfectioned, the next obstacle for the adequate progress of this
      surgery was the limited availability of anti-rejection drugs due to the fact that
      Ciclosporine has been and still is a drug of relative effectiveness. With the
      discovery of new anti-rejection drugs and with a best knowledge of the
      concomitant liver transplantation roll on the prognosis of these patients, it was
      possible to get in this decade, specifically in the last 2 years, extraordinary
      results; for example, from 170 pacients who underwent intestinal transplantation
      around the world, more than half were done by the University of Pittsburg. This
      university reported a survival of 62%. But, this percentage has been improved
      even more, the University of Miami reported a survival of 70% through the use of
      corticoides and two powerful anti-rejection drugs: FK-506 and Mycophelate.

PMID- 12219106
TI  - [DOUBLE PYLORUS: CASE REPORT AND REVIEW OF LITERATURE]
AB  - Double pylorus cases are extremely rare. Their etiology can be either congenital
      or acquired as complication of a peptic ulcer. Here we describe the first case
      diagnosed endoscopically in Cayetano Heredia National Hospital. A review of the
      literature regarding this anomaly is made as well as a discussion about its
      etiology.

PMID- 12219107
TI  - [MALIGNANT GASTRIC LEIOMYOBLASTOMA: CASE REPORT]
AB  - The gastric leiomyoblastoma is a benign neoplasia -extremely uncommon and
      potentially malignant-, which arises from the muscular layer of the stomach. We
      present the case of a 21 year old male patient with this disease, who suddenly
      had intraperitoneal hemorrhage. He underwent an exploratory operation and the
      surgical findings showed an ulcerated and bleeding nodular tumor, located on the
      anterior wall and minor curvature of the gastric antrum, ulcerated and with
      active bleeding. A distal subtotal gastrectomy was performed, as well as a
      Billroth II-type gastroenteroanastomosis from the Hoffmeister-Finsterer variety.
      The anatomopathologic report was, "malignant gastric leiomyoblastoma". We discuss
      the clinical features and therapeutical options used.

PMID- 12219108
TI  - Morbidity and survival in advanced AIDS in Rio de Janeiro, Brazil.
AB  - Opportunistic diseases (OD) are the most common cause of death in AIDS patients.
      To access the incidence of OD and survival in advanced immunodeficiency, we
      included 79 patients with AIDS treated at Hospital Evandro Chagas (FIOCRUZ) from
      September 1997 to December 1999 with at least one CD4 count <or=100 cells/mm(3).
      The incidence of OD was analyzed by Poisson's regression, and survival by Kaplan
      Meier and Cox analysis, considering a retrospective (before CD4 <or=100
      cells/mm(3)) and a prospective (after CD4 <or=100 cells/mm(3)) period, and
      controlling for demographic, clinical and laboratory characteristics. The
      confidence interval estipulated was 95%. Mean follow-up period was 733 days (CI =
      683-782). During the study 9 (11.4%) patients died. Survival from AIDS diagnosis
      was a mean of 2589 days (CI = 2363-2816) and from the date of the CD4 count CD4
      <or=100 cells/mm(3) was a mean of 1376 (CI = 1181-1572) days. Incidence of OD was
      0.51 pp/y before CD4 <or= 100 cells/mm(3) and 0.29 pp/y after CD4 <or= 100
      cells/mm(3). A lower number of ODs before CD4 < 100 cells/mm(3) was associated
      with lower incidence rates after CD4 <or= 100 cells/mm(3). AIDS diagnosis based
      on CD4+ counts <or= 200 cells/mm(3) was associated with lower incidence rates
      after CD4 <or= 100 cells/mm(3). Baseline CD4 counts above 50 cells/mm(3) (HR =
      0.13) and restoration of baseline CD4+ counts above 100 cells/mm(3) (HR = 0.16)
      were associated with a lower risk of death. Controlling both variables, only
      restoration of baseline counts was statistically significant (HR = 0.22, p =
      0.04). We found a very low incidence of OD and long survival after CD4 < 100
      cells/mm(3). Survival was significantly associated with restoration of baseline
      CD4 counts above 100 cells/mm(3).

PMID- 12219109
TI  - Study of chronic hemolytic anaemia patients in Rio de Janeiro: prevalence of anti
      human parvovirus B19 IgG antibodies and the development aplastic crises.
AB  - The prevalence of anti-human parvovirus B19 IgG antibodies was determined in sera
      from 165 chronic hemolytic anemia patients, receiving medical care at Instituto
      Estadual de Hematologia (IEHE), Rio de Janeiro, during the year of 1994. This
      sample represents around 10% of the chronic hemolytic anemia patients attending
      at IEHE. Most of these patients (140) have sickle cell disease. Anti-B19 IgG
      antibodies were detected in 32.1% of patients. No statistically significant
      difference (p > 0.05) was seen between IgG antibody prevalence in male (27.8%)
      and female (35.5%) patients. Anti-B19 IgG antibodies were more frequent in older
      (37.6%) than younger (28.2%) than 20 years old patients, although this difference
      had no statistical significance (p > 0.05). Anti-B19 IgG antibody prevalence
      showed that 67.9% of patients enrolled in the study were susceptible to B19 acute
      infection. With the aim to detect acute B19 infection, patients follow up
      continued until February 1996. During this period four patients presented
      transient aplastic crisis due to human parvovirus B19 as confirmed by the
      detection of specific IgM antibodies. All four patients were younger than 20
      years old, and 3 were younger than 10 years old. Three of them were sickle cell
      disease patients. Three of the four acute B19 infection occurred during 1994
      springtime.

PMID- 12219110
TI  - Biomphalaria tenagophila (Orbigny, 1835) (Mollusca): adaptation to desiccation
      and susceptibility to infection with Schistosoma mansoni Sambon, 1907.
AB  - Experiments were carried out to test the susceptibility of Biomphalaria
      tenagophila to the infection with strain SJ of Schistosoma mansoni in the F1, F2
      and non-selected parental generation. The potential adaptation of B. tenagophila
      to desiccation, in healthy mollusks and those exposed to the larvae of S. mansoni
      of the F1, F2 and non-selected parental generations was also studied. The
      presence of mucus and soil, at the shell opening, protected the snails against
      desiccation, favoring survival. The healthy mollusks performed more attempts
      against desiccation than those exposed to the larvae of the parasite. The
      mortality rate, during desiccation, was higher among mollusks that remained
      buried and with the shell opening unobstructed. During the desiccation period the
      stage of development of the parasite was influenced by the weight loss and the
      survival of the snails. The longer the period of desiccation, the greater was the
      weight loss observed, abbreviating survival. The non-selected parental generation
      was more sensitive to desiccation than the F1 and F2 generations, both in healthy
      mollusks and in those exposed to S. mansoni larvae. Healthy mollusks were more
      resistant to desiccation than those exposed to the larvae of the S. mansoni.
      Desiccation did not interrupt the development of S. mansoni larvae in mollusks,
      causing a delay in the cercariae elimination. The susceptibility of B.
      tenagophila to the SJ strain of S. mansoni, in mollusks maintained in water
      during the larvae incubation period, was similar in all three generations.

PMID- 12219111
TI  - Use of selective medium for Burkholderia cepacia isolation in respiratory samples
      from cystic fibrosis patients.
AB  - Burkholderia cepacia colonizes cystic fibrosis (CF) patients. We evaluated the
      impact of the use of a selective medium in the rate of B. cepacia recovery from
      respiratory samples of CF patients. During a 6-month period, respiratory samples
      were collected from 106 CF patients and cultivated on selective media including a
      B. cepacia selective medium. Confirmation of the identity of B. cepacia isolates
      was carried out by species specific PCR and determination of genomovar status
      performed by a sequential PCR approach. Results of B. cepacia isolation during
      this period were compared to the preceding two years, when the sample processing
      was identical except for the lack of the B. cepacia selective medium. B. cepacia
      was isolated in 11/257 (4.2%) of the samples using the selective medium, in
      contrast with the preceding two years, when it was isolated in 6/1029 samples
      (0.58%), p < 0.0001. Identity of all 11 isolates was confirmed by PCR and
      genomovar determination was accomplished in all but one isolate. These results
      suggest that the use of a selective medium increases recovery rate of B. cepacia
      from respiratory samples.

PMID- 12219112
TI  - Mycoplasma pneumoniae and Chlamydia pneumoniae in calcified nodules of aortic
      stenotic valves.
AB  - Aortic Valve Stenosis (AVS) has been explained as an atherosclerotic process of
      the valve as they often exhibit inflammatory changes with infiltration of
      macrophages, T lymphocytes and lipid infiltration. The present study investigated
      whether the bacteria Chlamydia pneumoniae (CP) and Mycoplasma pneumoniae (MP),
      detected previously in atherosclerotic plaques, are also present in AVS. Ten
      valves surgically removed from patients with AVS were analyzed by
      immunohistochemistry, in situ hybridization, and electron microscopy. The mean
      and standard deviation of the percentage areas occupied by CP antigens and MP -
      DNA were respectively 6.21 +/- 5.41 and 2.27 +/- 2.06 in calcified foci; 2.8 +/-
      3.33 and 1.78+/- 3.63 in surrounding fibrotic areas, and 0.21 +/- 0.17 and 0.12
      +/- 0.13 in less injured parts of the valve. There was higher amount of CP and MP
      in the calcified foci and in the surrounded fibrosis than in more preserved
      valvular regions. In conclusion, the fact that there were greater amounts of CP
      and MP in calcification foci of AVS favors the hypothesis that AS is not an
      inevitable degenerative process due to aging, but rather that it may be a
      response to the presence of these bacteria, similarly to the morphology detected
      in atherosclerosis damage.

PMID- 12219113
TI  - Identification of toxocara canis antigens by Western blot in experimentally
      infected rabbits.
AB  - Toxocariasis is a frequent helminthiasis that can cause visceral and ocular
      damage in humans specially in children. The identification of specific antigens
      of Toxocara canis is important in order to develop better diagnostic techniques.
      Ten rabbits were infected orally with a dose of 5000 Toxocara canis embryonated
      eggs. Rabbits were bled periodically and an ELISA assay was performed to
      determine levels of specific Toxocara IgG antibodies. ELISA detected antibodies
      at day 15 after infection. Western blot (WB) assay was performed using
      excretory/secretory antigens (E/S) of T. canis second stage larvae. Different
      antigen concentrations were evaluated: 150, 200, 250 and 300 micro g/mL. The
      concentration of 250 micro g/mL was retained for analysis. Rabbit sera were
      diluted 1:100. Secondary antibody was used at a dilution of 1:1000. Results of WB
      indicated that in the first month after infection specific antibodies against the
      200 KDa, 116 KDa, 92 KDa and 35 KDa antigens were detected; antibodies against
      the 92 KDa, 80 KDa, 66 KDa, 45 KDa, 31 KDa and 28 KDa antigens appeared later.
      All positive sera in the ELISA test were also positive in WB. Two antigen bands,
      92 KDa and 35 KDa, were identified since the beginning and throughout the course
      of infection. These antigens merit further evaluation as candidates for use in
      diagnosis.

PMID- 12219114
TI  - Infectious agents in coronary atheromas: a possible role in the pathogenesis of
      plaque rupture and acute myocardial infarction.
AB  - In this review we report our recent findings of histopathological features of
      plaque instability and the association with Mycoplasma pneumoniae (MP) and
      Chlamydia pneumoniae (CP) infection, studying thrombosed coronary artery segments
      (CAS) of patients who died due to acute myocardial infarction. Vulnerable plaques
      are known to be associated with fat atheromas and inflammation of the plaque.
      Here we demonstrated that vulnerability is also related with focal positive
      vessel remodeling that maintains relatively well preserved lumen even in the
      presence of large atheromatous plaques. This phenomena may explain why the
      cinecoronariography may not detect large and dangerous vulnerable plaques.
      Greater amount of these bacteria in vulnerable plaques is associated with
      adventitial inflammation and positive vessel remodeling: the mean numbers of
      lymphocytes were significantly higher in adventitia than in the plaque, good
      direct correlation was obtained between numbers of CD20 B cells and numbers of CP
      infected cells in adventitia, and between % area of MP-DNA in the plaque and
      cross sectional area of the vessel, suggesting a cause-effect relationship.
      Mycoplasma is a bacterium that needs cholesterol for proliferation and may
      increase virulence of other infectious agents. In conclusion, co-infection by
      Mycoplasma pneumoniae and Chlamydia pneumoniae may represent an important co
      factor for plaque instability, leading to coronary plaque thrombosis and acute
      myocardial infarction, since larger amount of these bacteria strongly correlated
      with histological signs of more vulnerability of the plaque. The search of CMV
      and Helicobacter pilori in these tissues resulted negative.

PMID- 12219115
TI  - Primary cutaneous cryptococcosis due to Cryptococcus neoformans var. gattii
      serotype B, in an immunocompetent patient.
AB  - The authors report a male patient, a seller with no detected immunosuppression,
      with an extensive ulcerated skin lesion localized on the left forearm, caused by
      Cryptococcus neoformans var. gattii serotype B. Oral treatment with fluconazole
      was successful. A review of the literature showed the rarity of this localization
      in HIV-negative patients. In contrast, skin lesions frequently occurs in HIV
      positive patients, with Cryptococcus neoformans var. neoformans serotype A
      predominating as the etiological agent. In this paper, the pathogenicity of C.
      neoformans to skin lesions in patients immunocompromised or not, is discussed,
      showing the efficacy of fluconazole for the treatment of these processes.

PMID- 12219116
TI  - Anti-Taenia solium metacestodes antibodies in serum from blood donors from four
      cities of Triangulo Mineiro area, Minas Gerais, Brazil, 1995.
AB  - Serological survey was performed to detect IgG antibodies anti-Taenia solium
      metacestodes in blood donors of Hemocentro Regional de Uberlandia, Minas Gerais,
      Brazil. A total of 1133 sera from blood donors coming from four cities of
      Triangulo Mineiro area were analyzed by the indirect fluorescence antibody test
      (IFAT) and the enzyme linked immunosorbent assay (ELISA). Specific IgG antibodies
      were found in 5.6% of the studied population, showing differences in the positive
      rates according to their origin: Araguari (13.5%), Tupaciguara (5.0%), Monte
      Alegre de Minas (4.8%) and Uberlandia (4.7%). The results indicate the probable
      endemicity of cysticercosis in this population.

PMID- 12219117
TI  - New prevalence estimate of TT virus (TTV) infection in low- and high-risk
      population from Sao Paulo, Brazil.
AB  - The prevalence of TT virus (TTV) infection was investigated by Polymerase Chain
      Reaction (PCR) in low- (blood donors and healthy children/adolescents) and high
      risk (hemophiliacs) groups from Sao Paulo, Brazil. Primers based on the
      untranslated region (UTR) of the viral genome proved to be much more ubiquitous,
      leading to much higher frequencies for both groups (>or= 81%) than the earlier
      N22-PCR directed to the open reading frame 1 (blood donors, 5.5%, and
      hemophiliacs, 42.3%). The UTR-PCR also revealed an interesting profile for
      healthy children/adolescents: very high prevalence at the early years and
      significant decrease in male teenagers. The N22-PCR, in turn, demonstrated higher
      frequency in hemophiliacs treated with fresh blood products (58%), than in those
      treated with virus-inactivated clotting factors (9.4%) and blood donors (5.5%).

PMID- 12219118
TI  - Isolation of Salmonella enterica and serologic reactivity to Leptospira
      interrogans in opossums (Didelphis virginiana) from Yucatan, Mexico.
AB  - The presence of Salmonella enterica and serologic evidence of infection by
      Leptospira interrogans, were detected in the opossum Didelphis virginiana in a
      semi-urban locality of the Yucatan State, Mexico. Ninety-one opossums were
      captured during the period April 1996 and May 1998. From a total of 17 feces
      samples, four Salmonella enterica subsp. enterica serotypes (Sandiego, Newport,
      Anatum, and Minnesota), and one Salmonella enterica subsp. arizonae serovar
      O44:Z4,Z23:- were isolated. Some opossums presented mixed infections. From 81
      sera samples, four (4.9%) were positive to antibodies to Leptospira serovars
      pomona and wolfii. Both animals infected with Salmonella enterica and those
      serologically positive to Leptospira interrogans were captured in peridomestic
      habitat. Opossums infected with Salmonella enterica, were captured in dry season,
      and those seropositive to Leptospira interrogans during the rainy season. The
      implications of infection and reactivity of these zoonotic pathogens in D.
      virginiana in the Yucatan state are briefly discussed.

PMID- 12219120
TI  - The impact of Chagas disease control in Latin America: a review.
AB  - Discovered in 1909, Chagas disease was progressively shown to be widespread
      throughout Latin America, affecting millions of rural people with a high impact
      on morbidity and mortality. With no vaccine or specific treatment available for
      large-scale public health interventions, the main control strategy relies on
      prevention of transmission, principally by eliminating the domestic insect
      vectors and control of transmission by blood transfusion. Vector control
      activities began in the 1940s, initially by means of housing improvement and then
      through insecticide spraying following successful field trials in Brazil (Bambui
      Research Centre), with similar results soon reproduced in Sao Paulo, Argentina,
      Venezuela and Chile. But national control programmes only began to be implemented
      after the 1970s, when technical questions were overcome and the scientific
      demonstration of the high social impact of Chagas disease was used to encourage
      political determination in favour of national campaigns (mainly in Brazil).
      Similarly, large-scale screening of infected blood donors in Latin America only
      began in the 1980s following the emergence of AIDS. By the end of the last
      century it became clear that continuous control in contiguous endemic areas could
      lead to the elimination of the most highly domestic vector populations -
      especially Triatoma infestans and Rhodnius prolixus - as well as substantial
      reductions of other widespread species such as T. brasiliensis, T. sordida, and
      T. dimidiata, leading in turn to interruption of disease transmission to rural
      people. The social impact of Chagas disease control can now be readily
      demonstrated by the disappearance of acute cases and of new infections in younger
      age groups, as well as progressive reductions of mortality and morbidity rates in
      controlled areas. In economic terms, the cost-benefit relationship between
      intervention (insecticide spraying, serology in blood banks) and the reduction of
      Chagas disease (in terms of medical and social care and improved productivity) is
      highly positive. Effective control of Chagas disease is now seen as an attainable
      goal that depends primarily on maintaining political will, so that the major
      constraints involve problems associated with the decentralisation of public
      health services and the progressive political disinterest in Chagas disease.
      Counterbalancing this are the political and technical cooperation strategies such
      as the "Southern Cone Initiative" launched in 1991. This international approach,
      coordinated by PAHO, has been highly successful, already reaching elimination of
      Chagas disease transmission in Uruguay, Chile, and large parts of Brazil and
      Argentina. The Southern Cone Initiative also helped to stimulate control
      campaigns in other countries of the region (Paraguay, Bolivia, Peru) which have
      also reached tangible regional successes. This model of international activity
      has been shown to be feasible and effective, with similar initiatives developed
      since 1997 in the Andean Region and in Central America. At present, Mexico and
      the Amazon Region remain as the next major challenges. With consolidation of
      operational programmes in all endemic countries, the future focus will be on
      epidemiological surveillance and care of those people already infected. In
      political terms, the control of Chagas disease in Latin America can be
      considered, so far, as a victory for international scientific cooperation, but
      will require continuing political commitment for sustained success.

PMID- 12219121
TI  - The opossum Didelphis virginiana as a synanthropic reservoir of Trypanosoma cruzi
      in Dzidzilche, Yucatan, Mexico.
AB  - In Mexico, the role of mammals in the transmission cycle of Trypanosoma cruzi is
      poorly known. In the State of Yucatan, an endemic area of Chagas disease, both
      Didelphis virginiana and D. marsupialis occur sympatrically. However, until now,
      only the former species had been found infected with T. cruzi. To evaluate the
      role of D. virginiana in a peridomestic transmission, nine periods of capture
      recapture were performed around the village of Dzidzilche, Yucatan. The sex, age,
      reproductive status, location, and presence of infection with T. cruzi were
      recorded for each opossum. The chromosome morphology was used to identify the
      opossum species. T. cruzi was identified by the presence of pseudocysts of
      amastigotes in cardiac muscle fibers of Balb/c mice inoculated with strains
      isolated from opossums. However, xenodiagnosis was the best diagnostic method.
      Triatoma dimidiata, the vector, were collected in and around the opossums' nests,
      and human dwellings; and were checked for T. cruzi. From 102 blood samples of D.
      virginiana examined 55 (53.9%) were positive to T. cruzi, the only two D.
      marsupialis captured were negative. Significant differences were found between
      infection, and both sex and reproductive condition. Eight out of 14 triatomines
      collected in peridomestic nests (57.1%), and 32 of 197 captured inside houses
      (16.3%) were found infected, suggesting a peridomestic transmission. The
      statistically high abundance of infected opossums and triatomines during the dry
      season (March to May) suggested the existence of a seasonality in the
      peridomestic transmission of T. cruzi in Dzidzilche.

PMID- 12219122
TI  - Freshwater snails and Schistosomiasis mansoni in the State of Rio de Janeiro,
      Brazil: II--Centro Fluminense Mesoregion.
AB  - During the course of a survey carried out from 2000 to 2001 in the Centro
      Fluminense Mesoregion of the State of Rio de Janeiro 22 molluscan species were
      found. Many of the records are new due to the dearth of previous studies.
      Concerning the snail hosts of Schistosoma mansoni, the most frequently
      encountered species was Biomphalaria tenagophila, as it occurred in all the
      surveyed municipalities. There are new records of Biomphalaria straminea and
      Biomphalaria peregrina which is regarded as a potential intermediate host.
      Drepanotrema lucidum and Antillorbis nordestensis were found to be shedding
      echinostome cercariae and strigid cercariae respectively. An account about the
      current schistosomiasis transmission sites in this Mesoregion is presented as
      well.

PMID- 12219123
TI  - Transmission of Leishmania in coffee plantations of Minas Gerais, Brazil.
AB  - Transmission of Leishmania was studied in 27 coffee plantations in the Brazilian
      State of Minas Gerais. Eighteen females and six males (11.6% of the people
      tested), aged between 7-65 gave a positive response to the Montenegro skin test.
      Awareness of sand flies based on the ability of respondents to identify the
      insects using up to seven predetermined characteristics was significantly greater
      among inhabitants of houses occupied by at least one Mn+ve individual. Five
      species of phlebotomine sand fly, including three suspected Leishmania vectors,
      were collected within plantations under three different cultivation systems. Four
      of these species i.e., Lu. fischeri (Pinto 1926), Lu. migonei (Franca 1920), Lu.
      misionensis (Castro 1959) and Lutzomyia whitmani (Antunes Coutinho 1939) were
      collected in an organic plantation and the last of these was also present in the
      other two plantation types. The remaining species, Lu. intermedia (Lutz Neiva
      1912), was collected in plantations under both the "adensado" and "convencional"
      systems. The results of this study indicate that transmission of Leishmania to
      man in coffee-growing areas of Minas Gerais may involve phlebotomine sand flies
      that inhabit plantations.

PMID- 12219124
TI  - Search for Borrelia sp. in ticks collected from potential reservoirs in an urban
      forest reserve in the State of Mato Grosso do Sul, Brazil: a short report.
AB  - A total of 128 ticks of the genus Amblyomma were recovered from 5 marsupials
      (Didelphis albiventris) - with 4 recaptures - and 17 rodents (16 Bolomys lasiurus
      and 1 Rattus norvegicus) captured in an urban forest reserve in Campo Grande,
      State of Mato Grosso do Sul, Brazil. Of the ticks collected, 95 (78.9%) were in
      larval form and 22 (21.1%) were nymphs; the only adult (0.8%) was identified as
      A. cajennense. Viewed under dark-field microscopy in the fourth month after
      seeding, 9 cultures prepared from spleens and livers of the rodents, blood of the
      marsupials, and macerates of Amblyomma sp. nymphs revealed spiral-shaped,
      spirochete-like structures resembling those of Borrelia sp. Some of them showed
      little motility, while others were non-motile. No such structures could be found
      either in positive Giemsa-stained culture smears or under electron microscopy. No
      PCR amplification of DNA from those cultures could be obtained by employing
      Leptospira sp., B. burgdorferi, and Borrelia sp. primers. These aspects suggest
      that the spirochete-like structures found in this study do not fit into the
      genera Borrelia or Leptospira, requiring instead to be isolated for proper
      identification.

PMID- 12219125
TI  - Seroepidemiological markers of enterically transmitted viral hepatitis A and E in
      individuals living in a community located in the North Area of Rio de Janeiro,
      RJ, Brazil.
AB  - We investigated the seroprevalence of hepatitis A virus (HAV) and hepatitis E
      virus (HEV) infection in subjects living in the community of Manguinhos, Rio de
      Janeiro, Brazil, and assisted at the Health Unit of Escola Nacional de Saude
      Publica, Fundacao Oswaldo Cruz. After formal consent, individuals were submitted
      to an interview using a standardized questionnaire. Anti-HAV and anti-HEV
      antibodies were detected by ELISA. Statistical analysis was carried out using the
      Epi-Info 6.04b software, to investigate possible associations between serological
      markers and risk factors. Results were regarded as significant when p value <
      0.05. Although a high prevalence of anti-HAV was observed (87%), almost 50% of
      subjects under the age of 10 were susceptible to HAV infection, an unexpected
      rate in endemic areas. This fact could be attributed to improvements in
      environmental sanitation, occurring in this area in the last years. The
      increasing proportion of susceptible people may result in outbreaks of HAV
      infection, since the virus still circulates in this area, as verified by the
      detection of anti-HAV IgM in some individuals. No statistical association was met
      between HAV infection and the risk factors here assessed. The anti-HEV IgG
      prevalence found in this population was 2.4%, consistent with the one found in
      non-endemic areas.

PMID- 12219126
TI  - Presence of American cutaneous Leishmaniasis vectors surrounding the city of
      Medellin, Colombia.
AB  - The presence of Lutzomyia (Helcocyrtomyia) hartmanni, as a vector of Leishmania
      colombiensis and L. columbiana (Verrucarum group), recently incriminated in the
      transmission of leishmaniasis, and L. pia (Verrucarum group) are reported for the
      first time in a periurban area of Medellin city. There is thus a risk of
      leishmaniasis transmission in this town.

PMID- 12219127
TI  - Prevalence of hepatitis C Virus infection among hemophiliacs in Central Brazil.
AB  - In order to investigate the hepatitis C virus (HCV) infection prevalence and risk
      factors in hemophiliacs in Central Brazil, 90 patients were interviewed and serum
      samples tested for HCV RNA and anti-HCV antibodies. An overall prevalence of
      63.3% (CI 95%: 53.0-72.7) was found. Multivariate analysis of risk factors showed
      that number of blood transfusions was significantly associated with this
      infection. Most hemophiliacs received locally produced cryoprecipitate. All
      infected patients were transfused before the screening of blood units for anti
      HCV. However, hemophiliacs who received exclusively screened cryoprecipitate were
      HCV negative. It confirms the expected decline in transfusion-acquired hepatitis
      C.

PMID- 12219128
TI  - Phlebotomine sand flies (Diptera: Psychodidae) associated with the appearance of
      urban Leishmaniasis in the city of Sincelejo, Colombia.
AB  - Although once associated only with rural areas, the American leishmaniasis
      vectors now appear to be associated also with urban and suburban areas of the
      Neotropics. Following the appearance of the first autochthonous visceral and
      cutaneous leishmaniasis cases in the urban area of the city of Sincelejo,
      Colombia, a preliminary entomological survey of the sand fly species composition
      was performed using Shannon and CDC light traps. A total of 486 sand flies
      representing six Lutzomyia species were collected. L. evansi, L. panamensis and
      L. gomezi, known vectors of Leishmania spp. were the predominant sand fly species
      around dwellings. The finding of these species in relation to the appearance of
      the first cases of leishmaniasis in the city mentioned is discussed.

PMID- 12219129
TI  - [Triatoma vandae sp.n. of the oliveirai complex from the State of Mato Grosso,
      Brazil (Hemiptera: Reduviidae: Triatominae)].
AB  - There are several specific complexes belonging to the genus Triatoma Laporte,
      1832, which are generally associated to specific geographic areas. Recent
      publications have linked the oliveirai complex to ecosystems of Mato Grosso,
      which are also present in other Brazilian states and even in other bordering
      countries as eastern Paraguay. The study of the abundant material collected
      during the last years allowed the description of several new species of the
      oliveirai complex: T. jurbergi Carcavallo, Galvao Lent, 1998; T. baratai
      Carcavallo Jurberg, 2000 and T. klugi Carcavallo, Jurberg, Lent Galvao, 2001.
      Another new species belonging to the same complex is described here as T. vandae
      sp.n. It originates from the state of Mato Grosso, and has been reared in the
      insectary of the Laboratorio Nacional e Internacional de Referencia em Taxonomia
      de Triatomineos, Departamento de Entomologia, Instituto Oswaldo Cruz-Fiocruz, Rio
      de Janeiro.

PMID- 12219130
TI  - A new species of Thelastomathidae (Nematoda) a parasite of Neocurtilla claraziana
      Saussure (Orthoptera, Gryllotalpidae) in Argentina.
AB  - Gryllophila cephalobulata n. sp. (Nematoda, Thelastomatidae) a parasite of the
      mole cricket Neocurtilla claraziana (Orthoptera, Gryllotalpidae) isolated in
      Buenos Aires Province, is described and illustrated. It is characterized by
      cuticle annulated all along the length of the body; the first ring has 4 lobules,
      the second one has 14 lobules, the others rings are simple, the stoma is short
      and has 4 small teeth, the genital papillae are arranged in 5 pairs, of which 3
      pairs are preanal and 2 pairs are postanal. The tail appendage of the male is
      long and filiform.

PMID- 12219131
TI  - Redescription of Travassiella avitellina Rego Pavanelli, 1987 (Proteocephalidea:
      Monticelliidae, Zygobothriinae), a parasite of Paulicea luetkeni (Siluriformes)
      from South America.
AB  - The genus Travassiella Rego Pavanelli, 1987 comprises only one species, T.
      avitellina Rego Pavanelli, 1987; characterized by these authors on the basis of
      absence of vitelline follicles. In this study, the presence of cortical vitelline
      follicles in this species is confirmed after de Chambrier and Vaucher (1999); the
      redescription was performed for the first time based on type and new material
      collected from Argentina, Brazil and Paraguay. Travassiella is confirmed as a
      valid genus, and compared to other genera of the subfamily Zygobothriinae. T.
      avitellina is characterized by: (1) the presence of gland cells posteromedially
      to suckers; (2) the particular distribution of vitelline follicles, forming
      lateral arches; (3) uterine primordium cortical, growing into medulla and forming
      a sac-like uterus; (4) eggs, irregularly oval, outer envelop with excrescences
      and two digitate lappets in one of the poles.

PMID- 12219132
TI  - Surface ultrastructure of third-instar Megaselia scalaris (Diptera: Phoridae).
AB  - We describe some ultrastructure of the third-instar Megaselia scalaris (Diptera:
      Phoridae) using scanning electron microscopy, with the cephalic segment, anterior
      spiracle and posterior spiracle being emphasized. This study provides the
      taxonomic information of this larval species, which may be useful to
      differentiate from other closely-related species.

PMID- 12219133
TI  - Geometric morphometric differences between Panstrongylus geniculatus from field
      and laboratory.
AB  - The finding of Panstrongylus geniculatus nymphs inside a house in northeastern
      Antioquia, Colombia, and the reports related to their increasing presence in
      homes suggest the need for surveillance methods for monitoring the invasion
      processes. We analyzed the morphological differences between a wild population
      and its laboratory descendants, using the techniques of geometric morphometry,
      with the idea that such differences might parallel those between sylvatic and
      synanthropic populations. The analyses over five generations showed differences
      in size but not in shape. Head size and wing size were both reduced from sylvatic
      to laboratory populations, but the decrease in head size occurred only up to the
      second generation while the decrease in wing size proceeded up to the fifth
      generation. In contrast, although a decrease in sexual size dimorphism has been
      proposed as a marker of colonization in human dwellings, we did not detect any
      significant loss of dimorphism between sexes of P. geniculatus over the five
      generations studied. We conclude that size changes may have a physiological
      origin in response to a change of ecotopes, but more than five generations may be
      required for the expression of permanent morphological markers of human dwellings
      colonization.

PMID- 12219134
TI  - Eye colour as a genetic marker for fertility and fecundity of Triatoma infestans
      (Klug, 1834) Hemiptera, Reduviidae, Triatominae.
AB  - Eye colour of Triatoma infestans is controlled at a single autosomal locus, with
      black-eye as the dominant gene and red-eye as the recessive. Inheritance of these
      characters follows a classical Mendelian system, enabling eye colour to be used
      as a marker for studies of mating frequency. We found no significant differences
      in oviposition rates and egg hatching rates irrespective of parental phenotypes.
      Different mating schedules between red-eye and black-eye parents showed that eye
      colour did not affect mating competence. Females mated with a single male or with
      different males together or in succession produced similar numbers of fertile
      eggs, with the eye colour of the offspring reflecting exposure to the different
      males. We conclude that although a single mating can provide sufficient sperm for
      the whole reproductive life of the female, multiple matings can result in
      balanced assortative sperm usage from the spermatheca.

PMID- 12219135
TI  - Effect of diflubenzuron on immature stages of Haematobia irritans (L.) (Diptera:
      Muscidae) in Uberlandia, State of Minas Gerais, Brazil.
AB  - Horn fly immatures were raised in media containing different concentrations of
      diflubenzuron in order to verify their susceptibility to this insect growth
      regulator (IGR). The 50% and 95% lethal concentrations of diflubenzuron for the
      population (LC50, LC95) were determined as well as the effect of this IGR on the
      different immature horn fly stages. The tests were performed using the progeny of
      adults collected in the field. The immatures were maintained in a growth chamber
      at 25.0 +/- 0.5oC and 12-12 h photoperiod. IGR concentrations of 300 ppb, 100 ppb
      and 50 ppb were lethal for 100% of the sample. Pupae malformation occurred in the
      breeding media containing different diflubenzuron concentrations. Values for
      LC50, LC95 (+/- 95% fiducial limits) and the slope of the regression line were
      respectively, 25.521 +/- 1.981 ppb, 34.650 +/- 2.001 ppb and 12.720 +/- 1.096.
      The third larval instar was more sensitive to the sub-lethal concentration of the
      product than the first and second ones were. The results indicate that this IGR
      can be an important tool for controlling horn fly populations as well as for
      managing horn fly resistance to conventional insecticides against Haematobia
      irritans in Uberlandia, State of Minas Gerais.

PMID- 12219136
TI  - Community ecology of the metazoan parasites of pink cusk-eel, Genypterus
      brasiliensis (Osteichthyes: Ophidiidae), from the coastal zone of the State of
      Rio de Janeiro, Brazil.
AB  - Fifty-five specimens of pink cusk-eel, Genypterus brasiliensis Regan, 1903
      (Osteichthyes: Ophidiidae) collected from the coastal zone of the State of Rio de
      Janeiro, Brazil (approx. 21-23 degrees S, 41-45 degrees W), from September 2000
      to January 2001, were necropsied to study their parasites. All fish were
      parasitized by one or more metazoan. Fourteen species of parasites were
      collected. G. brasiliensis is a new host record for nine parasite species. The
      larval stages of cestodes and the nematodes were the majority of the parasite
      specimens collected, with 38.4% and 36.5%, respectively. Cucullanus genypteri was
      the dominant species with highest prevalence and/or abundance. The parasites of
      G. brasiliensis showed the typical overdispersed pattern of distribution. Six
      parasite species showed correlation between the host's total body length and
      prevalence and abundance. Host sex did not influence prevalence and parasite
      abundance of any parasite species. The mean diversity in the infracommunities of
      G. brasiliensis was H= 0.364 +/- 0.103, with correlation with the host's total
      length and without differences in relation to sex of the host. One pair of adult
      endoparasites (C. genypteri and A. brasiliensis) showed positive covariations
      between their abundances. Negative association or covariation was not found.
      Differences between the qualitative and quantitative aspects of the parasite
      community of G. brasiliensis from Rio de Janeiro and Argentina suggest the
      existence of two population stocks of pink cusk-eel in the South America Atlantic
      Ocean.

PMID- 12219137
TI  - Polytene chromosome map and inversion polymorphism in Drosophila mediopunctata.
AB  - Drosophila mediopunctata belongs to the tripunctata group, and is one of the
      commonest Drosophila species collected in some places in Brazil, especially in
      the winter. A standard map of the polytene chromosomes is presented. The
      breakpoints of the naturally occurring chromosomal rearrangements are marked on
      the map. The distribution of breaking points through the chromosomes of D.
      mediopunctata is apparently non-random. Chromosomes X, II and IV show inversion
      polymorphisms. Chromosome II is the most polymorphic, with 17 inversions, 8
      inversions in the distal region and 9 in the proximal region. Chromosome X has
      four different gene arrangements, while chromosome IV has only two.

PMID- 12219138
TI  - Intergenic and external transcribed spacers of ribosomal RNA genes in lizard
      infecting Leishmania: molecular structure and phylogenetic relationship to mammal
      infecting Leishmania in the subgenus Leishmania (Leishmania).
AB  - To establish the relationships of the lizard- and mammal-infecting Leishmania, we
      characterized the intergenic spacer region of ribosomal RNA genes from L.
      tarentolae and L. hoogstraali. The organization of these regions is similar to
      those of other eukaryotes. The intergenic spacer region was approximately 4 kb in
      L. tarentolae and 5.5 kb in L. hoogstraali. The size difference was due to a
      greater number of 63-bp repetitive elements in the latter species. This region
      also contained another element, repeated twice, that had an inverted
      octanucleotide with the potential to form a stem-loop structure that could be
      involved in transcription termination or processing events. The ribosomal RNA
      gene localization showed a distinct pattern with one chromosomal band (2.2 Mb)
      for L. tarentolae and two (1.5 and 1.3 Mb) for L. hoogstraali. The study also
      showed sequence differences in the external transcribed region that could be used
      to distinguish lizard Leishmania from the mammalian Leishmania. The intergenic
      spacer region structure features found among Leishmania species indicated that
      lizard and mammalian Leishmania are closely related and support the inclusion of
      lizard-infecting species into the subgenus Sauroleishmania proposed by Saf'janova
      in 1982.

PMID- 12219139
TI  - Fibrogenesis and collagen resorption in the heart and skeletal muscle of Calomys
      callosus experimentally infected with Trypanosoma cruzi: immunohistochemical
      identification of extracellular matrix components.
AB  - Intense inflammatory lesions and early development of interstitial fibrosis of
      the myocardium and skeletal muscle with spontaneous regression, have been
      described in Calomys callosus infected with Trypanosoma cruzi. The genetic types
      of collagen present in this model were investigated through immunohistochemistry
      using specific antibodies, combined with histopathology and Picro-Sirius staining
      of collagen. Thirty-five calomys were infected with the Colombian strain of T.
      cruzi and sacrificed at 24, 30, 40, 60 and 90 days post-infection. Inflammatory
      lesions and fibrogenesis were prominent at the early phase of infection and
      significantly decreased during late infection. Immunoisotyping of the matrix
      components was performed by indirect immunofluorescence on 5 micro m thick
      cryostat sections using specific antibodies against laminin, fibronectin and
      isotypes I, III and IV of collagen. In the early phase, positive deposits of all
      the matrix components were present, with predominance of fibronectin, laminin and
      collagens types I and III in the myocardium and of types III and IV in the
      skeletal muscles. From the 40th day, type IV collagen predominates in the heart.
      At the late phase of infection (60th to 90th day), a clear fragmentation and
      decrease of all the matrix components were detected. Findings of the present
      study indicate that a modulation of the inflammatory process occurs in the model
      of C. callosus, leading to spontaneous regression of fibrosis independent of the
      genetic types of collagen involved in this process.

PMID- 12219140
TI  - Schistosoma mansoni heat shock protein 70 elicits an early humoral immune
      response in S. mansoni infected baboons.
AB  - A study was undertaken to search for DNA recombinant Schistosoma mansoni proteins
      responsible for eliciting an antibody response from the host at a very early
      phase after infection. A S. mansoni adult worm cDNA expression library was
      screened using pooled sera from baboons with four weeks of infection. Based on
      their specific reactivity with the S. mansoni infected sera and no reactivity
      when tested against the pre-infection sera from the same baboons, four clones
      were selected for further studies. Sequence analysis revealed that they were
      homologous to the S. mansoni heat shock protein 70 (hsp70). The insert sizes of
      the four selected clones varied from 1150 to 2006 bp. The preliminary
      characterization for antibody reactivity against a panel of baboon sera showed
      that the longest clone was the most reactive, eight out of eight acute and three
      out of four chronic sera reacting positively to this clone. The shortest clone
      was the least reactive. Our results suggest that the S. mansoni hsp70 elicits an
      early and strong antibody response in baboons and that antibodies to this protein
      can be detected in chronically infected animals. Therefore S. mansoni hsp70 may
      be a valid target for immunodiagnosis. However further studies are needed to
      identify the portion of the hsp70 that best fits the requirements for a valuable
      diagnostic antigen.

PMID- 12219141
TI  - Ultrastructural alterations in adult Schistosoma mansoni caused by artemether.
AB  - Progress has been made over the last decade with the development and clinical use
      of artemether as an agent against major human schistosome parasites. The tegument
      has been identified as a key target of artemether, implying detailed studies on
      ultrastructural damage induced by this compound. We performed a temporal
      examination, employing a transmission electron microscope to assess the pattern
      and extent of ultrastructural alterations in adult Schistosoma mansoni harboured
      in mice treated with a single dose of 400 mg/kg artemether. Eight hours post
      treatment, damage to the tegument and subtegumental structures was seen.
      Tegumental alterations reached a peak 3 days after treatment and were
      characterized by swelling, fusion of distal cytoplasma, focal lysis of the
      tegumental matrix and vacuolisation. Tubercles and sensory organelles frequently
      degenerated or collapsed. Typical features of subtegumental alterations,
      including muscle fibres, syncytium and parenchyma tissues, were focal or
      extensive lysis, vacuolisation and degeneration of mitochondria. Severe
      alterations were also observed in gut epithelial cells and vitelline cells of
      female worms. Our findings of artemether-induced ultrastructural alterations in
      adult S. mansoni confirm previous results obtained with juvenile S. mansoni and
      S. japonicum of different ages.

PMID- 12219142
TI  - Non-tuberculous mycobacteria I: one year clinical isolates identification in
      Tertiary Hospital Aids Reference Center, Rio de Janeiro, Brazil, in pre highly
      active antiretroviral therapy era.
AB  - The aim of this study was to determine the prevalence of non-tuberculous
      mycobacteria (NTM) isolates at University Hospital, Reference Center for Aids in
      Rio de Janeiro, Brazil, during one year. We used standard biochemical tests for
      species identification and IS1245 PCR amplification was applied as a
      Mycobacterium avium specific identification marker. Four hundred and four
      specimens from 233 patients yielded acid-fast bacilli growth. M. tuberculosis was
      identified in 85% of the patients and NTM in 15%. NTM disseminated infection was
      a common event correlated with human immunodeficiency virus (HIV) infected
      patients and only in HIV negative patients the source of NTM was non sterile
      site. M. avium complex (MAC) was biochemically identified in 57.8% (49/83) of NTM
      isolates, most of them from sterile sites (75.5%), and in 94% (46/49) the IS 1245
      marker specific for M. avium was present. Twenty NTM strains showed a MAC
      biochemical pattern with the exception of a urease-positive (99% of MAC are
      urease-negative), however IS1245 was detected in 96% of the strains leading to
      their identification as M. avium. In this group differences in NTM source was not
      significant. The second most frequently isolated NTM was identified as M.
      scrofulaceum (7.2%), followed by M. terrae (3.6%), M. gordonae (2.4%), M.
      chelonae (1.2%), M. fortuitum (1.2%) and one strain which could not be
      identified. All were IS1245 negative except for one strain identified as M.
      scrofulaceum. It is interesting to note that non-sterile sites were the major
      source of these isolates (92.8%). Our finding indicated that M. avium is still
      the major atypical species among in the MAC isolates recovered from Brazilian
      Aids patients without highty active antiretroviral therapy schema. Some
      discrepancies were seen between the identification methods and further
      investigations must be done to better characterize NTM isolates using other
      phenotypic and genotypic methods.

PMID- 12219143
TI  - Performance of OptiMAL(R) in the diagnosis of Plasmodium vivax and Plasmodium
      falciparum infections in a malaria referral center in Colombia.
AB  - Alternative, non-microscopic methods for the diagnosis of malaria have recently
      become available. Among these, rapid dipstick methods stand out. One such test,
      OptiMAL(R), is based on the immunochromatographic detection of Plasmodium lactate
      dehydrogenase (pLDH) and has the capacity to detect and distinguish infections
      caused by P. falciparum and Plasmodium sp. This capacity is particularly
      important in countries where different species of Plasmodium co-exist. In this
      study we evaluated the performance of OptiMAL(R) in an urban referral center for
      malaria diagnosis. Two sets of patients were included: one (n = 112) having
      predetermined infections with P. falciparum or P. vivax and individuals with
      negative blood smears; and another consisting of all eligible consecutive
      patients (n = 80) consulting for diagnosis at the referral center during one
      month. The overall diagnostic efficiency of OptiMAL(R) for both sets of patients
      was 96.9%. Efficiency was higher for P. vivax (98.1%) than for P. falciparum
      (94.9%). These results corroborate the diagnostic utility of OptiMAL(R) in
      settings where P. vivax and P. falciparum co-exist and support its implementation
      where microscopic diagnosis is unavailable and in circumstances that exceed the
      capacity of the local microscopic diagnosis facility.

PMID- 12219144
TI  - Preliminary assays indicate that Antonia ovata (Loganiaceae) and Derris amazonica
      (Papilionaceae), ichthyotoxic plants used for fishing in Roraima, Brazil, have an
      insecticide effect on Lutzomyia longipalpis (Diptera: Psychodidae:
      Phlebotominae).
AB  - Laboratory-reared Lutzomyia longipalpis (Lutz and Neiva 1912) was tested with
      extracts of two ichthyotoxic plants, known as timbos, used as fishing poison in
      the Amazon. Phlebotomines, L. longipalpis, and plants, Antonia ovata and Derris
      amazonica, were collected in the Raposa-Serra do Sol Indian Reserve, a focus of
      visceral leishmaniasis in the State of Roraima, Brazil. Extracts were prepared
      from dried leaves of A. ovata and roots of D. amazonica that were percolated in
      water, filtered and dried out at 50 degrees C. The solid extract obtained was
      diluted in water at 150, 200 and 250 mg/ml. The solution was blotted in filter
      paper placed at the bottom of cylindric glass tubes containing sand flies. For
      each plant extract and dilution, two series of triplicates with 5 male and 5
      female specimens of L. longipalpis were used. Mortality was recorded every 2 h
      during 72 h of exposure. At 72 h the mortality was as high as 80% for extracts of
      A. ovata (LD50 = 233 mg/ ml), and 100% for D. amazonica (LD50 = 212 mg/ ml)
      whereas in the control groups maximum mortality never surpassed 13%. Preliminary
      assays indicated that A. ovata and D. amazonica displayed significant insecticide
      effect against L. longipalpis.

PMID- 12219145
TI  - The molluscicidal activity of niclosamide (Bayluscide WP70(R)) on Melanoides
      tuberculata (Thiaridae), a snail associated with habitats of Biomphalaria
      glabrata (Planorbidae).
AB  - The aim of this study was to determine the toxicity of niclosamide (Bayluscide
      (R)) on Melanoides tuberculata and Biomphalaria glabrata under laboratory
      conditions. The latter species is the intermediate host of Schistosoma mansoni
      (Sambon 1917). M. tuberculata was successfully used as competitor of B. glabrata
      in biological control programs in French West Indies. Both molluscicide and
      biological control using M. tuberculata have proved to be successful in reducing
      the population density of B. glabrata. The associated use of molluscicide in this
      area would be an effective measure if M. tuberculata were less susceptibility to
      the molluscicide than B. glabrata. Three hundreds individuals each of B. glabrata
      and of M. tuberculata, collected in Sumidouro, State of Rio de Janeiro, were used
      in the experiment. The molluscs were exposed to 14 different concentrations of
      niclosamide as recommended by the World Health Organization. Probit analysis was
      used to determine the LC 50 and LC 90. The LC 50 and LC 90 values for B. glabrata
      were 0.077 mg/l and 0.175 mg/l, respectively and the LC 50 and LC 90 values for
      M. tuberculata were 0.082 mg/l and 0.221 mg/l respectively. As the lethal
      concentrations of niclosamide were approximately the same to both species, this
      could be a disadvantage when controlling B. glabrata with niclosamide in an area
      of M. tuberculata occurrence. It might therefore be preferable to utilize the
      latex extracted from the Euphorbia splendens, which presented a much higher
      efficiency for B. glabrata than to M. tuberculata.

PMID- 12219146
TI  - Clinical and mycological study of scalp white piedra in the State of Paraiba,
      Brazil.
AB  - White piedra is a superficial mycoses characterized by nodules on the hair shaft,
      caused by the basidiomycetous yeasts. In the present study, clinical and
      mycological findings of scalp white piedra caused by Trichosporon spp. are
      related. Twenty three cases of scalp white piedra were observed with a high
      incidence in women (87%) and preschool children from 2 to 6 (74%) years old.
      These groups presented a relationship of dependence with this infection. Despite
      the low socio-economic status, poor standards of hygiene, (48% of the patients)
      as well as the fact that 30.4% of the children shared the same nursery, these
      factors were not significant for the transmission of the mycosis. These were the
      first reports of scalp white piedra in Joao Pessoa city, Paraiba, Brazil.

PMID- 12219147
TI  - Concurrent cutaneous, visceral and ocular leishmaniasis caused by Leishmania
      (Viannia) braziliensis in a kidney transplant patient.
AB  - Although cases of leishmaniasis co-infection have been described in acquired
      immunodeficiency syndrome patients as well as those who have undergone organ
      transplants, to our knowledge, the present report is the first documented case of
      simultaneous cutaneous, visceral and ocular leishmaniasis due to Leishmania
      (Viannia) braziliensis in a transplant patient. The patient had been using
      immunosuppressive drugs since receiving a transplanted kidney. The first clinical
      signs of leishmaniasis included fever, thoracic pain, hepatosplenomegaly,
      leucopenia and anemia. The cutaneous disease was revealed by the presence of
      amastigotes in the skin biopsy. After three months, the patient presented fever
      with conjunctive hyperemia, intense ocular pain and low visual acuity. Parasites
      isolated from iliac crest, aqueous humor and vitreous body were examined using a
      range of molecular techniques. The same strain of L. (V.) braziliensis was
      responsible for the different clinical manifestations. The immunosuppressive
      drugs probably contributed to the dissemination of Leishmania.

PMID- 12219148
TI  - Influence of specific treatment on the morbidity of Schistosomiasis mansoni in an
      endemic area of Minas Gerais, Brazil.
AB  - The authors describe the evolution of schistosomiasis mansoni in inhabitants of
      Capitao Andrade, Minas Gerais, Brazil, from 1973 to 1994. The prevalence of
      infection was 60.8% in 1973, 36.2% in 1984, and 27.3% in 1994. The evolution of
      the clinical forms of the disease in this group was as follows: unchanged in
      76.7%, clinical progression in 8.4% and clinical regression in 14.9%. The
      reduction of the prevalence and severity of Schistosoma mansoni infection over
      the 21 years period, can be attributed to treatment of infected subjects
      performed in the area and to the installation of piped water in their dwellings.

PMID- 12219149
TI  - Epidemiological evidence: improving validity through consistency analysis.

PMID- 12219150
TI  - Preventing impoverishment through protection against catastrophic health
      expenditure.

PMID- 12219151
TI  - Reduction of catastrophic health care expenditures by a community-based health
      insurance scheme in Gujarat, India: current experiences and challenges.
AB  - OBJECTIVE: To assess the Self Employed Women's Association's Medical Insurance
      Fund in Gujarat in terms of insurance coverage according to income groups,
      protection of claimants from costs of hospitalization, time between discharge and
      reimbursement, and frequency of use. METHODS: One thousand nine hundred and
      thirty claims submitted over six years were analysed. FINDINGS: Two hundred and
      fifteen (11%) of 1927 claims were rejected. The mean household income of
      claimants was significantly lower than that of the general population. The
      percentage of households below the poverty line was similar for claimants and the
      general population. One thousand seven hundred and twelve (1712) claims were
      reimbursed: 805 (47%) fully and 907 (53%) at a mean reimbursement rate of 55.6%.
      Reimbursement more than halved the percentage of catastrophic hospitalizations
      (>10% of annual household income) and hospitalizations resulting in
      impoverishment. The average time between discharge and reimbursement was four
      months. The frequency of submission of claims was low (18.0/1000 members per
      year: 22-37% of the estimated frequency of hospitalization). CONCLUSIONS: The
      findings have implications for community-based health insurance schemes in India
      and elsewhere. Such schemes can protect poor households against the uncertain
      risk of medical expenses. They can be implemented in areas where institutional
      capacity is too weak to organize nationwide risk-pooling. Such schemes can cover
      poor people, including people and households below the poverty line. A trade off
      exists between maintaining the scheme's financial viability and protecting
      members against catastrophic expenditures. To facilitate reimbursement,
      administration, particularly processing of claims, should happen near claimants.
      Fine-tuning the design of a scheme is an ongoing process - a system of monitoring
      and evaluation is vital.

PMID- 12219152
TI  - The use of models in the estimation of disease epidemiology.
AB  - OBJECTIVE: To explore the usefulness of incidence-prevalence-mortality (IPM)
      models in improving estimates of disease epidemiology. METHODS: Two artificial
      and four empirical data sets (for breast, prostate, colorectal, and stomach
      cancer) were employed in IPM models. FINDINGS: The internally consistent
      artificial data sets could be reproduced virtually identically by the models. Our
      estimates often differed considerably from the empirical data sets, especially
      for breast and prostate cancer and for older ages. Only for stomach cancer did
      the estimates approximate to the data, except at older ages. CONCLUSION: There is
      evidence that the discrepancies between model estimates and observations are
      caused both by data inaccuracies and past trends in incidence or mortality.
      Because IPM models cannot distinguish these effects, their use in improving
      disease estimates becomes complicated. Expert opinion is indispensable in
      assessing whether the use of these models improves data quality or,
      inappropriately, removes the effect of trends.

PMID- 12219153
TI  - Is there an association between female circumcision and perinatal death?
AB  - OBJECTIVE: In Sweden, a country with high standards of obstetric care, the high
      rate of perinatal mortality among children of immigrant women from the Horn of
      Africa raises the question of whether there is an association between female
      circumcision and perinatal death. METHOD: To investigate this, we examined a
      cohort of 63 perinatal deaths of infants born in Sweden over the period 1990-96
      to circumcised women. FINDINGS: We found no evidence that female circumcision was
      related to perinatal death. Obstructed or prolonged labour, caused by scar tissue
      from circumcision, was not found to have any impact on the number of perinatal
      deaths. CONCLUSION: The results do not support previous conclusions that genital
      circumcision is related to perinatal death, regardless of other circumstances,
      and suggest that other, suboptimal factors contribute to perinatal death among
      circumcised migrant women.

PMID- 12219154
TI  - Determining median urinary iodine concentration that indicates adequate iodine
      intake at population level.
AB  - OBJECTIVE: Urinary iodine concentration is the prime indicator of nutritional
      iodine status and is used to evaluate population-based iodine supplementation. In
      1994, WHO, UNICEF and ICCIDD recommended median urinary iodine concentrations for
      populations of 100- 200 micro g/l, assuming the 100 micro g/l threshold would
      limit concentrations <50 micro g/l to </=20% of people. Some scientists felt this
      proportion was unacceptably high and wanted to increase the threshold above 100
      micro g/l. The study was carried out to determine the frequency distribution of
      urinary iodine in iodine-replete populations (schoolchildren and adults) and the
      proportion of concentrations <50 micro g/l. METHOD: A questionnaire on frequency
      distribution of urinary iodine in iodine-replete populations was circulated to 29
      scientific groups. FINDINGS: Nineteen groups reported data from 48 populations
      with median urinary iodine concentrations >100 micro g/l. The total population
      was 55 892, including 35 661 (64%) schoolchildren. Median urinary iodine
      concentrations were 111-540 (median 201) micro g/l for all populations, 100-199
      micro g/l in 23 (48%) populations and >/=200 micro g/l in 25 (52%). The
      frequencies of values <50 micro g/l were 0-20.8 (mean 4.8%) overall and 7.2% and
      2.5% in populations with medians of 100-199 micro g/l and >200 micro g/l,
      respectively. The frequency reached 20% only in two places where iodine had been
      supplemented for <2 years. CONCLUSION: The frequency of urinary iodine
      concentrations <50 micro g/l in populations with median urinary iodine
      concentrations >/=100 micro g/l has been overestimated. The threshold of 100
      micro g/l does not need to be increased. In populations, median urinary iodine
      concentrations of 100-200 micro g/l indicate adequate iodine intake and optimal
      iodine nutrition.

PMID- 12219155
TI  - Evaluation of the national control of diarrhoeal disease programme in the
      Philippines, 1980-93.
AB  - OBJECTIVE: To evaluate the impact of the National Control of Diarrhoeal Disease
      Programme (NCDDP) in the Philippines over the period 1980-93, describing levels
      and trends in programme activities, and relating them to severe diarrhoea
      morbidity and mortality among under-5-year-olds. METHODS: Routinely collected
      data on morbidity and mortality trends were obtained from health statistics
      reports of the Health Intelligence Service and the NCDDP. Socioeconomic
      indicators, including annual average family income and expenditures, gross
      national product, and unemployment rates, were derived from the Philippine
      population census data collected by the National Statistics Office. FINDINGS: In
      relation to baseline levels, diarrhoea mortality among infants and young children
      fell by about 5% annually over the 18-year period under review. The decline was
      faster than those related to acute respiratory infections (ARIs) among children
      of similar age and to perinatal causes. Diarrhoea hospital admission rates
      registered an annual decline of 2.4% relative to the baseline level. CONCLUSION:
      These findings suggest that the programme had a substantial impact; the period
      under review also witnessed some degree of improvement in other factors with
      positive influences on health, such as exclusive breastfeeding, nutrition and
      environmental sanitation. The quality, particularly completeness and reliability,
      of the existing data did not allow further analysis, thus, making it difficult to
      conclude beyond doubt that the observed trends indicate that they were solely due
      to NCDDP.

PMID- 12219156
TI  - Cross-national comparability of burden of disease estimates: the European
      Disability Weights Project.
AB  - OBJECTIVE: To investigate the sources of cross-national variation in disability
      adjusted life-years (DALYs) in the European Disability Weights Project. METHODS:
      Disability weights for 15 disease stages were derived empirically in five
      countries by means of a standardized procedure and the cross-national differences
      in visual analogue scale (VAS) scores were analysed. For each country the burden
      of dementia in women, used as an illustrative example, was estimated in DALYs. An
      analysis was performed of the relative effects of cross-national variations in
      demography, epidemiology and disability weights on DALY estimates. FINDINGS:
      Cross-national comparison of VAS scores showed almost identical ranking orders.
      After standardization for population size and age structure of the populations,
      the DALY rates per 100000 women ranged from 1050 in France to 1404 in the
      Netherlands. Because of uncertainties in the epidemiological data, the extent to
      which these differences reflected true variation between countries was difficult
      to estimate. The use of European rather than country-specific disability weights
      did not lead to a significant change in the burden of disease estimates for
      dementia. CONCLUSIONS: Sound epidemiological data are the first requirement for
      burden of disease estimation and relevant between-countries comparisons. DALY
      estimates for dementia were relatively insensitive to differences in disability
      weights between European countries.

PMID- 12219157
TI  - Cost of malaria control in China: Henan's consolidation programme from community
      and government perspectives.
AB  - OBJECTIVE: To assist with strategic planning for the eradication of malaria in
      Henan Province, China, which reached the consolidation phase of malaria control
      in 1992, when only 318 malaria cases were reported. METHODS: We conducted a
      prospective two-year study of the costs for Henan's malaria control programme. We
      used a cost model that could also be applied to other malaria programmes in
      mainland China, and analysed the cost of the three components of Henan's malaria
      programme: suspected malaria case management, vector surveillance, and population
      blood surveys. Primary cost data were collected from the government, and data on
      suspected malaria patients were collected in two malaria counties (population 2
      093 100). We enlisted the help of 260 village doctors in six townships or former
      communes (population 247 762), and studied all 12 325 reported cases of suspected
      malaria in their catchment areas in 1994 and 1995. FINDINGS: The average annual
      government investment in malaria control was estimated to be US$ 111 516 (case
      management 59%; active blood surveys 25%; vector surveillance 12%; and
      contingencies and special projects 4%). The average cost (direct and indirect)
      for patients seeking treatment for suspected malaria was US$ 3.48, equivalent to
      10 days' income for rural residents. Each suspected malaria case cost the
      government an average of US$ 0.78. CONCLUSION: Further cuts in government funding
      will increase future costs when epidemic malaria returns; investment in malaria
      control should therefore continue at least at current levels of US$ 0.03 per
      person at risk.

PMID- 12219158
TI  - Control of malaria: a successful experience from Viet Nam.
AB  - OBJECTIVE: To follow malaria prospectively in an ethnic minority commune in the
      south of Viet Nam with high malaria transmission and seasonal fluctuation, during
      malaria control interventions using insecticide-treated bednets (ITBNs) and early
      diagnosis and treatment (EDT) of symptomatic patients. METHODS: From 1994 onwards
      the following interventions were used: distribution of ITBNs to all households
      with biannual reimpregnation; construction of a health post and appointment of
      staff trained in microscopic diagnosis and treatment of malaria; regular supply
      of materials and drugs; annual cross-sectional malaria surveys with treatment of
      all parasitaemic subjects, and a programme of community involvement and health
      education. Surveys were held yearly at the end of the rainy season. During the
      surveys, demographic data were updated. Diagnosis and treatment of malaria were
      free of charge. Plasmodium falciparum infection was treated with artesunate and
      P. vivax infection with chloroquine plus primaquine. FINDINGS: The baseline
      survey in 1994 recorded 716 inhabitants. Of the children under 2 years of age,
      37% were parasitaemic; 56% of children aged 2-10 years, and 35% of the remaining
      population were parasitaemic. P. falciparum accounted for 73-79% of these
      infections. The respective splenomegaly rates for the above-mentioned age groups
      were 20%, 56%, and 32%. In 1999, the proportion of parasitaemic subjects was 4%,
      7% and 1%, respectively, of which P.falciparum contributed 56%. The splenomegaly
      rate was 0%, 5% and 2%, respectively. CONCLUSIONS: A combination of ITBNs and
      EDT, provided free of charge, complemented by annual diagnosis and treatment
      during malaria surveys and community involvement with health education
      successfully brought malaria under control. This approach could be applied to
      other regions in the south of Viet Nam and provides a sound basis for further
      studies in other areas with different epidemiological patterns of malaria.

PMID- 12219159
TI  - Reproductive health and health sector reform in developing countries:
      establishing a framework for dialogue.
AB  - It is not clear how policy-making in the field of reproductive health relates to
      changes associated with programmes for the reform of the health sector in
      developing countries. There has been little communication between these two
      areas, yet policy on reproductive health has to be implemented in the context of
      structural change. This paper examines factors that limit dialogue between the
      two areas and proposes the following framework for encouraging it: the
      identification of policy groups and the development of bases for collaborative
      links between them; the introduction of a common understanding around relevant
      policy contexts; reaching agreement on compatible aims relating to reproductive
      health and health sector change; developing causal links between policy content
      in reproductive health and health sector change as a basis for evidence-based
      policy-making; and strengthening policy-making structures, systems, skills, and
      values.

PMID- 12219160
TI  - Improving equity in the provision of primary health care: lessons from
      decentralized planning and management in Namibia.
AB  - This paper draws lessons from a review of primary health care services in
      Windhoek, the capital of Namibia, undertaken by a regional health management
      team. The review was carried out because of perceived increases in workload and
      inadequate staffing levels, arising from the rapid expansion of the city
      associated with inward migration. A survey of the utilization of government
      clinics was used to develop a more equitable allocation of primary health care
      services between localities. The survey revealed disparities between patterns of
      utilization of the services and the allocation of staff: the poorer localities
      were relatively underprovided. Decisions made centrally on resource allocation
      had reinforced the inequities. On the basis of the results of the review, the
      regional health management team redistributed nursing and medical staff and
      argued for a shift in the allocation of capital expenditure towards the poorer
      communities. The review demonstrates the potential for regional and provincial
      health management teams to make effective assessments of the needs of their
      populations and to promote the equitable delivery of primary health care
      services. In order to achieve this they need not only to become effective
      managers, but also to develop population-based planning skills and the confidence
      and authority to influence the allocation of resources between and within their
      regions and provinces.

PMID- 12219161
TI  - No quick fix for social science in public health.

PMID- 12219162
TI  - Mumbai slum dwellers' sewage project goes nationwide.

PMID- 12219164
TI  - New malaria drug candidate could cure in a single dose.

PMID- 12219165
TI  - AIDS could dominate Russian budget by 2020.

PMID- 12219167
TI  - Childhood blindness prevention project launched.

PMID- 12219166
TI  - HIV/AIDS deepens food crisis in southern Africa.

PMID- 12219168
TI  - Europe to be certified free of polio.

PMID- 12219169
TI  - New treatment for leishmaniasis is 95% effective.

PMID- 12219170
TI  - New cancer report reveals neglected opportunities.

PMID- 12219171
TI  - WHO to promote genetic services.

PMID- 12219172
TI  - Recent advances in angiotensin II signaling.
AB  - Angiotensin II (Ang II) is a multifunctional hormone that influences the function
      of cardiovascular cells through a complex series of intracellular signaling
      events initiated by the interaction of Ang II with AT1 and AT2 receptors. AT1
      receptor activation leads to cell growth, vascular contraction, inflammatory
      responses and salt and water retention, whereas AT2 receptors induce apoptosis,
      vasodilation and natriuresis. These effects are mediated via complex, interacting
      signaling pathways involving stimulation of PLC and Ca2+ mobilization; activation
      of PLD, PLA2, PKC, MAP kinases and NAD(P)H oxidase, and stimulation of gene
      transcription. In addition, Ang II activates many intracellular tyrosine kinases
      that play a role in growth signaling and inflammation, such as Src, Pyk2,
      p130Cas, FAK and JAK/STAT. These events may be direct or indirect via
      transactivation of tyrosine kinase receptors, including PDGFR, EGFR and IGFR. Ang
      II induces a multitude of actions in various tissues, and the signaling events
      following occupancy and activation of Ang receptors are tightly controlled and
      extremely complex. Alterations of these highly regulated signaling pathways may
      be pivotal in structural and functional abnormalities that underlie pathological
      processes in cardiovascular diseases such as cardiac hypertrophy, hypertension
      and atherosclerosis.

PMID- 12219173
TI  - Interaction between paraventricular nucleus and septal area in the control of
      physiological responses induced by angiotensin II.
AB  - We determined the effects of losartan (40 nmol) and PD 123319 (40 nmol) (both non
      peptides and selective antagonists of the AT1 and AT2 angiotensin receptors,
      respectively), and [Sar1, Ala8] angiotensin II (ANG II) (40 nmol) (a non
      selective peptide antagonist of angiotensin receptors) injected into the
      paraventricular nucleus (PVN) on the water and salt appetite, diuresis and
      natriuresis and mean arterial pressure (MAP) induced by administration of 10 nmol
      of ANG II into the medial septal area (MSA) of male Holtzman rats weighing 250
      300 g. The volume of drug solution injected was 0.5 micro l over a period of 10
      15 s. The responses were measured over a period of 120 min. ANG II alone injected
      into the MSA induced an increase in all the above parameters (8.1 +/- 1.2, 1.8 +/
      0.3, and 17.1 +/- 1.0 ml, 217 +/- 25 micro Eq/120 min, and 24 +/- 4 mmHg,
      respectively, N = 10-12) compared with vehicle-treated rats (1.4 +/- 0.2, 0.6 +/-
      0.1, and 9.3 +/- 0.5 ml, 47 +/- 5 micro Eq/120 min, and 4.1 +/- 0.8 mmHg,
      respectively, N = 10-14). Pretreatment with losartan and [Sar1, Ala8] ANG II
      completely abolished the water and sodium intake, and the pressor increase (0.5
      +/- 0.2, 1.1 +/- 0.2, 0.5 +/- 0.2, and 0.8 +/- 0.2 ml, and 1.2 +/- 3.9, 31 +/-
      4.6 mmHg, respectively, N = 9-12), whereas losartan blunted the urinary and
      sodium excretion induced by ANG II (13.9 +/- 1.0 ml and 187 +/- 10 micro Eq/120
      min, respectively, N = 9). Pretreatment with PD 123319 and [Sar1, Ala8] ANG II
      blocked the urinary and sodium excretion (10.7 +/- 0.8, 9.8 +/- 0.7 ml, and 67 +/
      13 and 57 +/- 17 micro Eq/120 min, respectively, N = 9), whereas pretreatment
      with PD 123319 partially blocked the water and sodium intake, and the MAP induced
      by ANG II administration (2.3 +/- 0.3, 1.1 +/- 0.1 ml, and 12 +/- 3 mmHg,
      respectively, N = 9-10). These results suggest the angiotensinergic effect of the
      MSA on the AT1 and AT2 receptors of the PVN in terms of water and sodium
      homeostasis and MAP modulation.

PMID- 12219174
TI  - Chronic converting enzyme inhibition normalizes QT interval in aging rats.
AB  - The aim of the present study was to investigate the effects of converting enzyme
      inhibition by captopril on ECG parameters in aged rats. Four-month-old male rats
      received captopril dissolved in tap water (0.5 mg/l) or tap water for 2 or 20
      months. At the end of treatment, under anesthesia, RR and PR interval, P wave and
      QRS duration, QT and corrected QT interval were measured in all animals. On the
      following day, chronic ECG (lead II) recordings were performed to quantify
      supraventricular (SVPB) or ventricular premature beats (VPB). After sacrifice,
      the hearts were removed and weighed. RR interval was similar in young and
      untreated aged rats, but significantly larger in aged rats treated with
      captopril. P wave and QRS length did not differ among groups. PR interval was
      significantly larger in old than in young rats and was not affected by captopril.
      Corrected QT interval was larger in aged than in young rats (117 +/- 4 vs 64 +/-
      6 ms, P<0.05) and was reduced by captopril (71 +/- 6 ms, P<0.05). VPB were absent
      in young rats and highly frequent in untreated old animals (8.4 +/- 3.0/30 min).
      Captopril significantly reduced VPB in old rats (0.3 +/- 0.1/30 min, P<0.05). The
      cardiac hypertrophy found in untreated aged rats was prevented by captopril (3.44
      +/- 0.14 vs 3.07 +/- 0.10 mg/g, P<0.05). The beneficial effects of angiotensin
      converting enzyme inhibition on the rat heart during the aging process are
      remarkable.

PMID- 12219175
TI  - Role of sensory nervous system vasoactive peptides in hypertension.
AB  - The goal of the present research was to elucidate the roles and mechanisms by
      which the sensory nervous system, through the actions of potent vasodilator
      neuropeptides, regulates cardiovascular function in both the normal state and in
      the pathophysiology of hypertension. The animal models of acquired hypertension
      studied were deoxycorticosterone-salt (DOC-salt), subtotal nephrectomy-salt (SN
      salt), and Nomega-nitro-L-arginine methyl ester (L-NAME)-induced hypertension
      during pregnancy in rats. The genetic model was the spontaneously hypertensive
      rat (SHR). Calcitonin gene-related peptide (CGRP) and substance P (SP) are potent
      vasodilating neuropeptides. In the acquired models of hypertension, CGRP and SP
      play compensatory roles to buffer the blood pressure (BP) increase. Their
      synthesis and release are increased in the DOC-salt model but not in the SN-salt
      model. This suggests that the mechanism by which both models lower BP in SN-salt
      rats is by increased vascular sensitivity. CGRP functions in a similar manner in
      the L-NAME model. In the SHR, synthesis of CGRP and SP is decreased. This could
      contribute to the BP elevation in this model. The CGRP gene knockout mouse has
      increased baseline mean arterial pressure. The long-term synthesis and release of
      CGRP is increased by nerve growth factor, bradykinin, and prostaglandins and is
      decreased by alpha2-adrenoreceptor agonists and glucocorticoids. In several
      animal models, sensory nervous system vasoactive peptides play a role in chronic
      BP elevation. In the acquired models, they play a compensatory role. In the
      genetic model, their decreased levels may contribute to the elevated BP. The
      roles of CGRP and SP in human hypertension are yet to be clarified.

PMID- 12219176
TI  - Angiotensin and baroreflex control of the circulation.
AB  - There is a close association between the location of angiotensin (Ang) receptors
      and many important brain nuclei involved in the regulation of the cardiovascular
      system. The present review encompasses the physiological role of Ang II in the
      brainstem, particularly in relation to its influence on baroreflex control of the
      heart and kidney. Activation of AT1 receptors in the brainstem by fourth
      ventricle (4V) administration to conscious rabbits or local administration of Ang
      II into the rostral ventrolateral medulla (RVLM) of anesthetized rabbits acutely
      increases renal sympathetic nerve activity (RSNA) and RSNA baroreflex responses.
      Administration of the Ang antagonist Sarile into the RVLM of anesthetized rabbits
      blocked the effects of Ang II on the RSNA baroreflex, indicating that the RVLM is
      the major site of sympathoexcitatory action of Ang II given into the
      cerebrospinal fluid surrounding the brainstem. However, in conscious animals,
      blockade of endogenous Ang receptors in the brainstem by the 4V AT1 receptor
      antagonist losartan resulted in sympathoexcitation, suggesting an overall greater
      activity of endogenous Ang II within the sympathoinhibitory pathways. However,
      the RSNA response to airjet stress in conscious rabbits was markedly attenuated.
      While we found no effect of acute central Ang on heart rate baroreflexes, chronic
      4V infusion inhibited the baroreflex and chronic losartan increased baroreflex
      gain. Thus, brainstem Ang II acutely alters sympathetic responses to specific
      afferent inputs thus forming part of a potentially important mechanism for the
      integration of autonomic response patterns. The sympathoexcitatory AT1 receptors
      appear to be activated during stress, surgery and anesthesia.

PMID- 12219177
TI  - Gender differences in vascular expression of endothelin and ET(A)/ET(B)
      receptors, but not in calcium handling mechanisms, in deoxycorticosterone acetate
      salt hypertension.
AB  - We determined if the increased vascular responsiveness to endothelin-1 (ET-1)
      observed in male, but not in female, DOCA-salt rats is associated with
      differential vascular mRNA expression of ET-1 and/or ET A/ET B receptors or with
      functional differences in Ca2+ handling mechanisms by vascular myocytes.
      Uninephrectomized male and female Wistar rats received DOCA and drinking water
      containing NaCl/KCl. Control rats received vehicle and tap water. Blood pressure
      and contractile responses of endothelium-denuded aortic rings to agents which
      induce Ca2+ influx and/or its release from internal stores were measured using
      standard procedures. Expression of mRNA for ET-1 and ET A/ET B receptors was
      evaluated by RT-PCR after isolation of total cell RNA from both aorta and
      mesenteric arteries. Systolic blood pressure was higher in male than in female
      DOCA rats. Contractions induced by Bay K8644 (which activates Ca2+ influx through
      voltage-operated L-type channels), and by caffeine, serotonin or ET-1 in Ca2+
      free buffer (which reflect Ca2+ release from internal stores) were significantly
      increased in aortas from male and female DOCA-salt compared to control aortas.
      DOCA-salt treatment of male, but not female, rats statistically increased
      vascular mRNA expression of ET-1 and ET B receptors, but decreased the expression
      of ET A receptors. Molecular up-regulation of vascular ET B receptors, rather
      than differential changes in smooth muscle Ca2+ handling mechanisms, seems to
      account for the increased vascular reactivity to ET-1/ET B receptor agonists and
      higher blood pressure levels observed in male DOCA-salt rats.

PMID- 12219178
TI  - Dissociation between the circulating renin-angiotensin system and angiotensin II
      receptors in central losartan-induced hypertension.
AB  - Losartan, an AT1 angiotensin II (ANG II) receptor non-peptide antagonist, induces
      an increase in mean arterial pressure (MAP) when injected
      intracerebroventricularly (icv) into rats. The present study investigated
      possible effector mechanisms of the increase in MAP induced by icv losartan in
      unanesthetized rats. Male Holtzman rats (280-300 g, N = 6/group) with a cannula
      implanted into the anterior ventral third ventricle received an icv injection of
      losartan (90 micro g/2 micro l) that induced a typical peak pressor response
      within 5 min. In one group of animals, this response to icv losartan was
      completely reduced from 18 +/- 1 to 4 +/- 2 mmHg by intravenous (iv) injection of
      losartan (2.5-10 mg/kg), and in another group, it was partially reduced from 18
      +/- 3 to 11 +/- 2 mmHg by iv prazosin (0.1-1.0 mg/kg), an alpha1-adrenergic
      antagonist (P<0.05). Captopril (10 mg/kg), a converting enzyme inhibitor,
      injected iv in a third group inhibited the pressor response to icv losartan from
      24 +/- 3 to 7 +/- 2 mmHg (P<0.05). Propranolol (10 mg/kg), a beta-adrenoceptor
      antagonist, injected iv in a fourth group did not alter the pressor response to
      icv losartan. Plasma renin activity and serum angiotensin-converting enzyme
      activity were not altered by icv losartan in other animals. The results suggest
      that the pressor effect of icv losartan depends on angiotensinergic and alpha1
      adrenoceptor activation, but not on increased circulating ANG II.

PMID- 12219179
TI  - Myocardial antioxidant and oxidative stress changes due to sex hormones.
AB  - The purpose of the present study was to examine myocardial antioxidant and
      oxidative stress changes in male and female rats in the presence of physiological
      sex hormone concentrations and after castration. Twenty-four 9-week-old Wistar
      rats were divided into four groups of 6 animals each: 1) sham-operated females,
      2) castrated females, 3) sham-operated males, and 4) castrated males. When
      testosterone and estrogen levels were measured by radioimmunoassay, significant
      differences were observed between the castrated and control groups (both males
      and females), demonstrating the success of castration. Progesterone and catalase
      levels did not change in any group. Control male rats had higher levels of
      glutathione peroxidase (50%) and lower levels of superoxide dismutase (SOD, 14%)
      than females. Control females presented increased levels of SOD as compared to
      the other groups. After castration, SOD activity decreased by 29% in the female
      group and by 14% in the male group as compared to their respective controls.
      Lipid peroxidation (LPO) was assessed to evaluate oxidative damage to cardiac
      membranes by two different methods, i.e., TBARS and chemiluminescence. LPO was
      higher in male controls compared to female controls when evaluated by both
      methods, TBARS (360%) and chemiluminescence (46%). Castration induced a 200%
      increase in myocardial damage in females as determined by TBARS and a 20%
      increase as determined by chemiluminescence. In males, castration did not change
      LPO levels. These data suggest that estrogen may have an antioxidant role in
      heart muscle, while testosterone does not.

PMID- 12219180
TI  - Angiotensin-(1-7) improves the post-ischemic function in isolated perfused rat
      hearts.
AB  - We evaluated the effects of angiotensin-(1-7) (Ang-(1-7)) on post-ischemic
      function in isolated hearts from adult male Wistar rats perfused according to the
      Langendorff technique. Local ischemia was induced by coronary ligation for 15
      min. After ischemia, hearts were reperfused for 30 min. Addition of angiotensin
      II (Ang II) (0.20 nM, N = 10) or Ang-(1-7) (0.22 nM, N = 10) to the Krebs-Ringer
      perfusion solution (KRS) before the occlusion did not modify diastolic or
      systolic tension, heart rate or coronary flow (basal values for Ang-(1-7)-treated
      hearts: 0.72 +/- 0.08 g, 10.50 +/- 0.66 g, 216 +/- 9 bpm, 5.78 +/- 0.60 ml/min,
      respectively). During the period of occlusion, the coronary flow, heart rate and
      systolic tension decreased (values for Ang-(1-7)-treated hearts: 2.83 +/- 0.24
      ml/min, 186 +/- 7 bpm, 6.95 +/- 0.45 g, respectively). During reperfusion a
      further decrease in systolic tension was observed in control (4.95 +/- 0.60 g)
      and Ang II-treated hearts (4.35 +/- 0.62 g). However, in isolated hearts perfused
      with KRS containing Ang-(1-7) the further reduction of systolic tension during
      the reperfusion period was prevented (7.37 +/- 0.68 g). The effect of Ang-(1-7)
      on the systolic tension was blocked by the selective Ang-(1-7) antagonist A-779
      (2 nM, N = 9), by the bradykinin B2 antagonist HOE 140 (100 nM, N = 10), and by
      indomethacin pretreatment (5 mg/kg, ip, N = 8). Pretreatment with L-NAME (30
      mg/kg, ip, N = 8) did not change the effect of Ang-(1-7) on systolic tension
      (6.85 +/- 0.61 g). These results show that Ang-(1-7) at low concentration (0.22
      nM) improves myocardial function (systolic tension) in ischemia/reperfusion
      through a receptor-mediated mechanism involving release of bradykinin and
      prostaglandins.

PMID- 12219181
TI  - Cardiovascular control in experimental diabetes.
AB  - Several studies have reported impairment in cardiovascular function and control
      in diabetes. The studies cited in this review were carried out from a few days up
      to 3 months after streptozotocin administration and were concerned with the
      control of the circulation. We observed that early changes (5 days) in blood
      pressure control by different peripheral receptors were maintained for several
      months. Moreover, the impairment of reflex responses observed after baroreceptor
      and chemoreceptor stimulation was probably related to changes in the efferent
      limb of the reflex arc (sympathetic and parasympathetic), but changes also in the
      central nervous system could not be excluded. Changes in renal sympathetic nerve
      activity during volume expansion were blunted in streptozotocin-treated rats,
      indicating an adaptive natriuretic and diuretic response in the diabetic state.
      The improvement of diabetic cardiovascular dysfunction induced by exercise
      training seems to be related to changes in the autonomic nervous system.
      Complementary studies about the complex interaction between circulation control
      systems are clearly needed to adequately address the management of
      pathophysiological changes associated with diabetes.

PMID- 12219182
TI  - Nitrergic modulation of vasopressin, oxytocin and atrial natriuretic peptide
      secretion in response to sodium intake and hypertonic blood volume expansion.
AB  - The central nervous system plays an important role in the control of renal sodium
      excretion. We present here a brief review of physiologic regulation of
      hydromineral balance and discuss recent results from our laboratory that focus on
      the participation of nitrergic, vasopressinergic, and oxytocinergic systems in
      the regulation of water and sodium excretion under different salt intake and
      hypertonic blood volume expansion (BVE) conditions. High sodium intake induced a
      significant increase in nitric oxide synthase (NOS) activity in the medial basal
      hypothalamus and neural lobe, while a low sodium diet decreased NOS activity in
      the neural lobe, suggesting that central NOS is involved in the control of sodium
      balance. An increase in plasma concentrations in vasopressin (AVP), oxytocin
      (OT), atrial natriuretic peptide (ANP), and nitrate after hypertonic BVE was also
      demonstrated. The central inhibition of NOS by L-NAME caused a decrease in plasma
      AVP and no change in plasma OT or ANP levels after BVE. These data indicate that
      the increase in AVP release after hypertonic BVE depends on nitric oxide
      production. In contrast, the pattern of OT secretion was similar to that of ANP
      secretion, supporting the view that OT is a neuromodulator of ANP secretion
      during hypertonic BVE. Thus, neurohypophyseal hormones and ANP are secreted under
      hypertonic BVE in order to correct the changes induced in blood volume and
      osmolality, and the secretion of AVP in this particular situation depends on NOS
      activity.

PMID- 12219183
TI  - Study of coronary sinus flow reserve through transesophageal Doppler
      echocardiography in normal subjects.
AB  - OBJECTIVE: To evaluate the Coronary Flow Reserve in the Coronary Sinus through
      transesophageal Doppler echocardiography in normal subjects. METHODS: We obtained
      technically adequate flow samples for analysis in 10 healthy volunteers (37+/-8
      years, 5 men) with no history of heart or systemic disease and with mean left
      ventricular mass index by transthoracic echocardiography of 87+/-18 g/m2.
      Coronary sinus flow velocity was recorded within the coronary sinus with the
      patient in a resting condition and during intravenous adenosine infusion at a
      dose of 140 micro g/kg/min for 4 minutes. Recording of coronary sinus blood flow
      was possible in all cases with measurement of peak systolic, diastolic, and
      retrograde velocities (PSV, PDV, and PRV, cm/sec), mean systolic and diastolic
      velocities (MSV and MDV, cm/sec), and systolic and diastolic velocity time
      integral (VTI S and VTI D, cm/sec). RESULTS: The coronary flow reserve was
      calculated as the ratio between the blood flow in the basal state and the maximum
      measured hyperemic blood flow with adenosine infusion. Results are shown as mean
      and standard deviations. (CFR = PSV + PDV - PRV/basal PSV): 1st min = 2.2+/-0.21;
      2nd min = 3+/-0.3; 3rd min = 3.4+/-0.37; 4th min = 3.6 +/- 0.33. CONCLUSION:
      Although coronary sinus flow had significantly increased in the first minute,
      higher velocities were seen at third and fourth minutes, indicating that these
      should be the best times to study coronary sinus flow with intravenous adenosine
      in continuous infusion.

PMID- 12219184
TI  - Late results of endoventricular patch plasty repair in akinetic and dyskinetic
      areas after acute myocardial infarction.
AB  - OBJECTIVE: To assess the surgical results of endoventricular patch plasty repair
      in akinetic and dyskinetic left ventricular areas. METHODS: We studied 52
      patients who had undergone endoventricular patch plasty repair associated with
      myocardial revascularization. The preoperative functional class distribution was
      as follows: class I in 1 (1.9%) patient; class II in 2 (3.8%) patients; class III
      in 23 (44.2%) patients; and class IV in 26 (50%) patients. RESULTS: The immediate
      mortality rate was 7.6% (4 patients). The clinical outcome of 44 patients
      followed up within a mean postoperative time of 29+/-25 months was as follows:
      class I in 33 (75%) patients; class II in 7 (15.9%) patients; class III in 2
      (4.5%) patients; and class IV in 2 (4.5%) patients. Comparison between pre- and
      postoperative catheterization in 21 patients showed that the ejection fraction
      increased from 46.3% to 51.3% (p=0.17); the left ventricular systolic volume
      decreased from 76.4 mL to 57.5 mL, (p=0.078); and the left ventricular diastolic
      volume decreased from 141.2 mL to 105.8 mL (p=0.0 73). These findings showed the
      tendency toward improvement, but with nonsignificant results. CONCLUSION: The
      technique proved to be effective, to have a low mortality rate, to cause
      significant clinical improvement, an increase in ejection fraction, and a
      reduction in left ventricular volumes.

PMID- 12219185
TI  - Cross-sectional study on blood pressure control in the department of nephrology
      of the Escola Paulista de Medicina - UNIFESP.
AB  - OBJECTIVE: To assess hypertension control rates in a specialized university
      affiliated medical department, the influence of sex, diabetes, and obesity on
      that control, and the strategies for the treatment of hypertension. METHODS: We
      carried out a cross-sectional study with 1,210 patients followed up for at least
      6 months. Information was gathered from medical and nursing records and comprised
      the following data: sex, age, weight, height, abdominal and hip circumferences,
      blood pressure, and class and number of the antihypertensive drugs prescribed. To
      assess obesity, we used body mass index and waist/hip ratio. Blood pressure was
      considered under control when its levels were below 140/90 mmHg. RESULTS: The
      study consisted of 73% females and 27% males. Most females (31.7%) were 50 to 59
      years of age, and most males (28.3%) were 60 to 69 years. The blood pressure
      control rate found was 20.9% for the 1,210 patients and 23.4% for the
      hypertensive diabetic patients (n=290). Despite the low control rates found, 70%
      of the patients used 1 or 2 antihypertensive medications. A high prevalence of
      obesity (38%) was observed, and females had a greater abdominal obesity index
      than males did (90% vs 82%, p<0.05). Patients with a greater body mass index had
      less control of blood pressure. CONCLUSION: The percentage of hypertensive
      patients with controlled blood pressure levels was low and was associated with a
      high prevalence of obesity. These data indicate the need for reviewing the
      strategies of global treatment for hypertension.

PMID- 12219186
TI  - Initial energy for external electrical cardioversion of atrial fibrillation.
AB  - OBJECTIVE: To investigate the initial energy level required for electrical
      cardioversion of atrial fibrillation (AF). METHODS: We studied patients
      undergoing electrical cardioversion in the 1st Multicenter Trial of SOCESP.
      Patients were divided into 2 groups according to the initial energy level of
      electrical cardioversion: 100J and >/=150J. We compared the efficacy of the
      initial and final shock of the procedure, the number of shocks administered, and
      the cumulative energy levels. RESULTS: Eight-six patients underwent electrical
      cardioversion. In 53 patients (62%), cardioversion was started with 100J, and in
      33 patients (38%), cardioversion was started with >/=150J. Groups did not differ
      regarding clinical features and therapeutical interventions. A tendency existed
      towards greater efficacy of the initial shock in patients who received >/=150J
      (61% vs. 42% in the 100J group, p=0.08). The number of shocks was smaller in the
      >/=150J group (1.5+/-0.7 vs. 2.1+/-1.3, p=0.04). No difference existed regarding
      the final efficacy of electrical cardioversion and total cumulative energy levels
      in both groups. In the subgroup of patients with recent-onset AF (</=48h), the
      cumulative energy level was lower in the 100J group (240+/-227J vs. 324+/-225J,
      p=0.03). CONCLUSION: Patients who were given initial energy of >/=150J received
      fewer counter shocks with a tendency toward greater success than those patients
      who were given 100J; however, in patients with recent-onset AF, the average
      cumulative energy level was lower in the 100J group. These data suggest that
      electrical cardioversion should be initiated with energy levels >/=150J in
      patients with chronic AF.

PMID- 12219187
TI  - [Food phytosterol ester efficiency on the plasma lipid reduction in moderate
      hypercholesterolemic subjects].
AB  - OBJECTIVE: This study aimed at relating the pattern of response to dietary plant
      sterol ester (PSE) treatment of plasma lipids concentrations and apo E
      polymorphisms. METHODS: Patients (20-60y old: 50 women; 10 men) with primary
      moderate hypercholesterolemia were fed margarine (20g/d), received no treatment
      (placebo), and were fed PSE (2.8g/d = 1.68 phytosterols), during 3 periods of 4
      weeks each, in a crossover, double-blind study. DNA was extracted from white
      blood cells for the apo E polymorphisms. RESULTS: PSE treatment significantly
      lowered TC and LDL-C 10% and 12%, respectively, in relation to the baseline, and
      6% and 8% in relation to the placebo phase, but HDL-C and TG levels were not
      modified. In regard to the apo E genotyping, no significant difference occurred
      between apo E 3/3 and apo E (3/4). CONCLUSION: Dietary plant sterol ester (PSE)
      treatment reduced cholesterolemia, and the reduction of LDL-C in absolute values
      was more pronounced when the initial LDL - C concentration were elevated.

PMID- 12219188
TI  - QRS voltage-duration product in the identification of left ventricular
      hypertrophy in spontaneously hypertensive rats.
AB  - OBJECTIVE: Evaluation of the performance of the QRS voltage-duration product
      (VDP) for detection of left ventricular hypertrophy (LVH) in spontaneously
      hypertensive rats (SHR). METHODS: Orthogonal electrocardiograms (ECG) were
      recorded in male SHR at the age of 12 and 20 weeks, when systolic blood pressure
      (sBP) reached the average values of 165+/-3 mmHg and 195+/-12 mmHg, respectively.
      Age- and sex- matched normotensive Wistar Kyoto (WKY) rats were used as controls.
      VDP was calculated as a product of maximum QRS spatial vector magnitude and QRS
      duration. Left ventricular mass (LVM) was weighed after rats were sacrificed.
      RESULTS: LVM in SHR at 12 and 20 weeks of age (0.86+/-0.05 g and 1.05+/-0.07 g,
      respectively) was significantly higher as compared with that in WKY (0.65+/-0.07
      g and 0.70+/-0.02 g). The increase in LVM closely correlated with the sBP
      increase. VDP did not reflect the increase in LVM in SHR. VDP was lower in SHR as
      compared with that in WKY, and the difference was significant at the age of 20
      weeks (18.2mVms compared with 10.7mVms, p<0.01). On the contrary, a significant
      increase in the VDP was observed in the control WKY at the age of 20 weeks
      without changes in LVM. The changes in VDP were influenced mainly by the changes
      in QRSmax. CONCLUSION: LVM was not the major determinant of QRS voltage changes
      and consequently of the VDP. These data point to the importance of the nonspatial
      determinants of the recorded QRS voltage in terms of the solid angle theory.

PMID- 12219189
TI  - Electrocardiographic and blood pressure alterations during electroconvulsive
      therapy in young adults.
AB  - OBJECTIVE: To study cardiovascular alterations in young patients with no apparent
      organic disease who underwent electroconvulsive therapy. METHODS: The study
      comprised 47 healthy patients (22 males and 25 females) with a mean age of 30.3
      years, who underwent electroconvulsive therapy. Ambulatory blood pressure
      monitoring and continuous electrocardiographic monitoring (Holter monitor) were
      performed during 24 hours. Blood pressure and heart rate were assessed 4 hours
      prior to electric shock administration, during electric shock administration, and
      3 hours after electric shock administration. Arrhythmias and alterations in the
      ST segment in 24 hours were recorded. RESULTS: On electroconvulsive therapy, a
      significant increase in blood pressure and heart rate was observed and the
      measurements returned to basal values after 25 minutes. Three females had
      tracings with depression of the ST segment suggesting myocardial ischemia prior
      to and after electroconvulsive therapy. Coronary angiography was normal. No
      severe cardiac arrhythmias were diagnosed. CONCLUSION: 1) Electroconvulsive
      therapy is a safe therapeutic modality in psychiatry; 2) it causes a significant
      increase in blood pressure and heart rate; 3) it may be associated with
      myocardial ischemia in the absence of coronary obstructive disease; 4)
      electroconvulsive therapy was not associated with the occurrence of severe
      cardiac arrhythmias.

PMID- 12219190
TI  - Analysis of plasma homocysteine levels in patients with unstable angina.
AB  - OBJECTIVE: To determine the prevalence of hyperhomocystinemia in patients with
      acute ischemic syndrome of the unstable angina type. METHODS: We prospectively
      studied 46 patients (24 females) with unstable angina and 46 control patients (19
      males), paired by sex and age, blinded to the laboratory data. Details of diets,
      smoking habits, medication used, body mass index, and the presence of
      hypertension and diabetes were recorded, as were plasma lipid and glucose levels,
      C-reactive protein, and lipoperoxidation in all participants. Patients with renal
      disease were excluded. Plasma homocysteine was estimated using high-pressure
      liquid chromatography. RESULTS: Plasma homocysteine levels were significantly
      higher in the group of patients with unstable angina (12.7+/-6.7 micromol/L) than
      in the control group (8.7+/-4.4 micromol/L) (p<0.05). Among males, homocystinemia
      was higher in the group with unstable angina than in the control group, but this
      difference was not statistically significant (14.1+/-5.9 micromol/L versus 11.9+/
      4.2 micromol/L). Among females, however, a statistically significant difference
      was observed between the 2 groups: 11.0+/-7.4 micromol/L versus 6.4+/-2.9
      micromol/L (p<0.05) in the unstable angina and control groups, respectively.
      Approximately 24% of the patients had unstable angina at homocysteine levels
      above 15 micromol/L. CONCLUSION: High homocysteine levels seem to be a relevant
      prevalent factor in the population with unstable angina, particularly among
      females.

PMID- 12219191
TI  - Arterial hypertension in a child with Williams-Beuren syndrome (7q11.23
      chromosomal deletion).
AB  - We report the case of a 7-year-old male child diagnosed with Williams-Beuren
      syndrome and arterial hypertension refractory to clinical treatment. The
      diagnosis was confirmed by genetic study. Narrowing of the descending aorta and
      stenosis of the renal arteries were also diagnosed. Systemic vascular alterations
      caused by deletion of the elastin gene may occur early in individuals with
      Williams-Beuren syndrome, leading to the clinical manifestation of systemic
      arterial hypertension refractory to drug treatment.

PMID- 12219192
TI  - Internal mammary to pulmonary artery fistula presenting as early recurrent angina
      after coronary bypass.
AB  - A 50-year-old man developed recurrent angina 1 year after coronary artery bypass
      surgery. The patient was found to have a large fistula involving branches of the
      internal mammary artery graft and the left pulmonary artery. In the absence of
      another clear cause for the patient's symptoms, we speculated that our patient's
      angina and abnormal stress nuclear study were due to coronary steal. In patients
      with a history of coronary bypass grafting, fistula formation between graft and
      native vessels should be considered as a possible cause of early recurrent
      angina.

PMID- 12219193
TI  - Retinal detachment in preeclampsia.
AB  - Preeclampsia is an obstetric disease of unknown cause that affects approximately
      5% of pregnant women. The visual system may be affected with variable intensity,
      being the retinal detachment a rare complication. The retinal detachment in
      preeclampsia is usually bilateral and serous, and its pathogenesis is related to
      the choroidal ischemia secondary to an intense arteriolar vasospasm. The majority
      of patients have complete recovery of vision with clinical management, and
      surgery is unnecessary. This is a case report of a 27 year old patient who
      developed the severe form of preeclampsia on her first pregnancy. She had
      progressive blurred vision, until she could see only shadows. Ophthalmic
      examination diagnosed spread and bilateral retinal detachment. With blood
      pressure control at postpartum, the patient had her retina reattached, and
      recovery of vision.

PMID- 12219194
TI  - [Why should nomenclature of congenital heart disease be systematized? ].

PMID- 12219195
TI  - [Anatomo-clinical correlation: Case 4/2002 - A 69 year-old female with myocardial
      infarction and shock in the postoperative period of myocardial revascularization
      (Instituto do Coracao do Hospital das Clinicas da FMUSP, Sao Paulo) ].

PMID- 12219196
TI  - [Clinic-radiographic correlation: Case 8/2002 - Instituto do Coracao do Hospital
      das Clinicas da FMUSP].

PMID- 12219197
TI  - Chest pain units: a modern way of managing patients with chest pain in the
      emergency department.
AB  - It is estimated that 5 to 8 million individuals with chest pain or other symptoms
      suggestive of myocardial ischemia are seen each year in emergency departments
      (ED) in the United States 1,2, which corresponds to 5 to 10% of all visits 3,4.
      Most of these patients are hospitalized for evaluation of possible acute coronary
      syndrome (ACS). This generates an estimated cost of 3 - 6 thousand dollars per
      patient 5,6. From this evaluation process, about 1.2 million patients receive the
      diagnosis of acute myocardial infarction (AMI), and just about the same number
      have unstable angina. Therefore, about one half to two thirds of these patients
      with chest pain do not have a cardiac cause for their symptoms 2,3. Thus, the
      emergency physician is faced with the difficult challenge of identifying those
      with ACS - a life-threatening disease - to treat them properly, and to discharge
      the others to suitable outpatient investigation and management.

PMID- 12219198
TI  - Studies of the Expression of Progesterone Receptor Gene in the Rat Uterus during
      Early Pregnancy by RT-PCR.
AB  - Progesterone plays an important role in the establishment and maintenance of
      pregnancy. However, there have been no systematic reports on the expression of
      the rat uterine progesterone receptor (PR) gene during this process. In the
      present studies PR mRNA levels in rat uterus were analyzed during the estrous
      cycle and early pregnancy (d1-d10), using reverse transcription-polymerase chain
      reaction (RT-PCR). PR mRNA level was the highest at estrus and the lowest at
      metestrus, with the former value twice the latter. Post-coitum PR transcription
      increased rapidly, reached a peak of two fold of the d1 level on d3-d4 (before
      implantation), but drastically dropped to 50% of the d1 level on d6 (during
      implantation) and remained unchanged until d10. It is of interest to discover
      that the uterine PR mRNA level at the implantational sites was much higher than
      that at the non-implantational sites on d7-d10. Preliminary discussion was made
      on the physiological significance of these changes.

PMID- 12219199
TI  - A Computer Model for the Pore of Potassium Channel: Oxygen Cage Mechanism.
AB  - We have constructed a structural motif for the pore of voltage-gated K(+) channel
      by computer modeling. The model developed here predicts that the narrowest part
      of the pore is formed by the four carbonyl oxygens of Gly444 or Gly446, and that
      the ion selectivity is achieved through "oxygen cage" mechanism. Residues 447,
      448 and 449 make the external entrance to the narrowest part of the pore. Of
      these residues, 449 and 447 are believed to interact directly with TEA. This
      model agrees well with many available experimental data.

PMID- 12219200
TI  - In vivo Induction of Rabbit 2',5'-Oligoadenylate Synthetase.
AB  - By the study of in vivo induction of rabbit 2',5'-oligoadenylate synthetase
      (2',5'-OASE), it has been found that polyinosinic acid-polycytidylic acid
      (poly(I).poly(C)) can induce the formation of 2',5'-OASE only in rabbit
      peripheral blood mononuclear cells(PBMC), whereas New Castle disease virus (NDV)
      and erythropoietin (EPO) are capable of enhancing 2',5'-OASE level in the total
      red blood capsule (RBC) as well as in PBMC. It has been demonstrated that the
      enzyme is located in reticulocytes and that the increase of 2',5'-OASE level by
      phenylhydrazine, NDV, EPO in RBC is proportionally related to the increase of
      reticulocytes. The level of 2',5'-OASE in PBMC from rabbit treated with
      poly(I).poly(C), NDV, EPO is 6 times higher than that of the control, suggesting
      an induction effect occurs. Considering that poly(I).poly(C) and NDV are highly
      efficient inducers of rabbit interferon and that the induction kinetics by EPO is
      similar to that by interferon, it is reasonable to postulate that the induction
      effect of the two former agents are mediated by interferon, while the latter
      initiates induction directly.

PMID- 12219201
TI  - A Comparative Study of Different Types of Rabbit 2',5'-Oligoadenylate Synthetase.
AB  - Only one 2',5'-oligoadenylate synthetase (2',5'-OASE) with a mass of 110 kD is
      present in the NDV-induced rabbit reticulocytes, whereas two 2',5'-OASE isozymes
      with mass of 110 kD and 40 kD respectively exist in the NDV-treated rabbit
      spleen. The large 110 kD enzymes from reticulocytes and spleen are associated
      with the ribosome. The small enzyme from spleen has been found in both the
      cytosol and ribosomal pellet. The characterization of the large enzymes purified
      from NDV-induced reticulocytes and spleen show that the 110 kD enzymes are the
      same one, and identical to the enzyme from phenylhydrazine-induced rabbit
      reticulocytes, suggesting that they are most likely encoded by the same gene,
      although their induction pathway and tissue distribution pattern are different.
      It is postulated that the 40 kD 2',5'-OASE from rabbit spleen and the large
      enzyme are isozymes with different physiological functions, considering that they
      require different conditions for catalytic reaction reaction and are located in
      different subcellular fractions.

PMID- 12219202
TI  - The Discovery of Streptomycin-binding IgG and Its Distribution in the Population.
AB  - It was found by using several immunochemistry methods that a kind of
      immunoglobulin G (IgG) which accounted for 0.5%-1% of the total IgG in human,
      rabbit or mice with no history of taking any streptomycin could bind specifically
      with the antibiotic. Although the IgG-binding action has not relation with the
      specificity of the antibody, the streptomycin-binding area was found to be on the
      antigen-binding region of Fab fragment of the antibody. This kind of IgG was
      termed streptomycin-binding IgG (SMBIgG) which may be capable of catalyzing the
      metabolism of streptomycin. The average content of SMBIgG in human and rabbit
      sera is about 0.1 mg/ml, with no samples with a lower level than the mean value,
      but in a few cases levels two or three times higher than the mean were detected.
      Further study indicated that the ratio of SMBIgG to total IgG is nearly constant
      in the population. The discovery of SMBIgG in the normal body and its catalytic
      characteristic may be very helpful for understanding some of the special
      physiological functions of the antibody in the organism.

PMID- 12219203
TI  - The Preparation of the Antigen Conformation-related Monoclonal Antibodies against
      Maltose-Binding Protein.
AB  - Making use of the high expression efficiency of maltose-binding protein (MBP) in
      E. coli, the soluble and the inclusion body forms of MBP were purified to
      homogeneity by affinity chromatography and by denaturation, refolding and gel
      filtration respectively. After immunized Balb/C mice with two forms of MBP
      respectively, 5 clones for each antigen form were found to secrete monoclonal
      antibodies. The binding experiments showed that two antibodies obtained by the
      immunization with the refolded form of MBP had high affinity to the denatured
      MBP.

PMID- 12219204
TI  - The Transferrins from Amphioxus and the Molecular Evolution of Transferrin.
AB  - An amphioxus transferring was isolated and purified from the Xiamen amphioxus.
      Its physio-chemical properties are the same as those of Qingdao amphioxus
      transferrin. It is a glyco-protein with a molecular weight of 26 kD that is about
      a quarter of that of the transferrin from vertebrates. Its partial amino acid
      sequence and its C-terminal fragment were determined. By comparison with the
      sequence of human serum transferrin, it has been found that the sequence of human
      serum transferrin can be divided into 4 fragments with about equal size as the
      sequences of the amphioxus transferrin. There is quite a high homology between
      the sequences of amphioxus transferrin and each of the 4 fragments as well as
      between the four fragments. The results demonstrate that the current transferrin
      may be evolved from an ancestor transferrin with one quarter of the molecular
      weight as a result of twice gene duplication. Amphioxus transferrin may be the
      representative from of such ancestor transferrin.

PMID- 12219205
TI  - DiO-C(18)-(3) Mediated Cell Fusion.
AB  - DiO, a fluorescent membrane probe, induced the rapid fusion of human erythrocytes
      and also mediated the fusion of mouse L-929 cells (fibroblastoma) in isotonic
      buffer (pH7.4) at room temperature. The fusion was independent of external Ca(2+)
      activating cysteine proteinase. PMSF, an inhibitor of serine proteinase, had no
      stopping effect on the fusion. The fluorescent cell images showed the existence
      of binding sites characteristic of high local concentration of DiO on the cell
      surface. Fluorescent filaments protruding from the cells and fused pairs were
      also recorded. These observations may have implication for a mechanism which
      promotes the protrusions of plasma membrane in the course of cell fusion. Based
      on the membrane electrostatics an the stress of the removal of water between
      bilayers, we infer that microregions of shared phospholipid bilayer may be formed
      at the distal ends of the protrusions when they are formed together as a
      consequence of the local dehydration action of the fusogen.

PMID- 12219206
TI  - Studies on the Separation, Purification of Beijing Duck Apo A-I CNBr Cleavaged
      Fragments and the Localization of Their Function Domain.
AB  - Apo A-I of Beijing duck was first cleavaged by CNBr into 11 peptide fragments
      which were further separated and purified by preparative SDS-PAGE and HPLC, then
      their molecular weights and N-terminal amino acid sequences were also determined.
      According to the molecular weights and N-terminal amino acid sequences of each
      fragment the positions of peptide fragments 3-10 in apo A-I molecule were
      localized at the sites of amino acid sequences 64-240, 74-240, 64-206, 1-163, 1
      36, 171-206, 207-240 and 137-170 respectively. The studied results of their main
      functions are as following: (1) All the fragments could combine with lipids to
      form lipsomes of various sizes. The fragment Longer, the size will be larger. (2)
      The ability of the fragments 3-10 to activate LCAT equals to 65%, 52%, 60%, 39%,
      8%, 7%, 0% and 2% of that of the whole apo A-I molecule respectively, showing
      that the activating sequence is localized in amino acid residues 64-136. (3) Only
      the liposomes formed with fragments 3, 4 and 9 could combine with the HDL
      receptor of liver cell membrane of Beijing duck; the rest of the liposomes
      demonstrated essentially no binding ability. As peptide fragments 3 and 4 also
      contained fragment 9, the result indicated that amino acids 207-240 maybe the
      fragment that combined with HDL receptor.

PMID- 12219207
TI  - Identification of an Embryonic Erythroid Nuclear Factor Binding to the Positive
      Stage-specific Regulatory Element of the Human epsilon-Globin Gene.
AB  - The erythroid- and developmental stage-specific expression of the human epsilon
      globin gene is controlled, in part, by the 5'-flanking DNA sequences of this
      gene. In the present study, a nuclear transacting factor of molecular weight
      about 80 kD epsilon-SSP in K562 cell (a human embryonic erythroid cell line) was
      identified by gel mobility shift assay, DNaseI footprinting assay and
      Southwestern blot assay. It could specifically bind to a positive stage-specific
      regulatory element (-446 bp to -419 bp, termed epsilon-PREII) of the human
      epsilon-globin gene. Our data suggested that this nuclear factor (termed epsilon
      SSP) might be an erythroid- and stage-specific protein. In addition, we observed
      that the shift band of this protein bound with the epsilon-PREII could be
      competed by DNA fragments derived from the human epsilon-globin gene promoter(
      177 bp to +1 bp), the DNaseI hypersensitive site 2 (-10 965 bp to -10 681 bp) and
      the hypersensitive site 3(-14 993 bp to -14 718 bp) of beta-LCR, suggesting that
      epsilon-SSP might be involved in the developmental regulation of human epsilon
      globin gene through the interaction between the proximal (promoter) and the
      distal (LCR) cis-acting elements.

PMID- 12219208
TI  - The Nucleotide Sequence of gltD Gene Encoding the Small Subunit of Rhodobacter
      sphaeroides Glutamate Synthase.
AB  - We have determined the complete nucleotide sequence of a 2 387 bp chromosomal
      SalI-EcoRI fragment, which contains the structural gene (gltD) for the small
      subunit of Rhodobacter sphaeroides glutamate synthase, as well as the 5'- and 3'
      flanking regions. An open reading frame of 1 242 base pairs was identified as the
      R. sphaeroides gltD gene. The MW of the small subunit, as deduced from the
      nucleotide sequence, was estimated to be 44 kD. A comparison of the nucleotide
      sequence revealed a high similarity among gltD genes of R. sphaeroides,
      Azospirillum brasilense and Escherichia coli. The deduced amino acid sequence of
      R. sphaeroides GltD showed a high similarity with that of A. brasilense GltD. The
      analysis of the binding domains of R. sphaeroides GltD was also carried out. The
      gltD-lacZ fusion was observed in the presence of 15 mM leucine.

PMID- 12219209
TI  - Expression of a Ligninase by a New Hybrid Baculovirus with Expanded Host Range.
AB  - We have generated and purified a new recombinant baculovirus with expanded host
      range. AcNPV DNA and BamHI-digested BmNPV DNA were co-transfected into Spodoptera
      frugiperda SF21 cells. Progeny viruses were used to infect BmN cells, which are
      normally resistant to AcNPV infection, in order to screen for recombinant viruses
      with cross-infectivity. A recombinant virus was isolated by plaque purification
      and analyzed. This isolate was able to infect, replicate and produce polyhedrin
      in both the SF21 and BmN cells. DNA restriction endonuclease analysis showed that
      it was a hybrid (HyNPV) of AcNPV and BmNPV. Co-transfection of this HyNPV virus
      with a transfer vector containing a ligninase H8 gene insert into SF21 cells
      yielded a recombinant baculovirus expressing the ligninase. When this recombinant
      baculovirus was used to infect either SF21 or BmN cells, ligninase proteins could
      be found in the lysed cells as well as in the cell culture media. We have thus
      demonstrated that this hybrid virus can be utilized in the generation of
      recombinant baculovirus expressing foreign proteins in two host cells which
      normally can not be infected by AcNPV nor BmNPV.

PMID- 12219210
TI  - Effects of Insulin and cAMP on the High Density Lipoprotein Receptor in Cultured
      Human Arterial Smooth Muscle Cells.
AB  - Effects of insulin and cyclic AMP (cAMP) on HDL binding to cultured human
      arterial smooth muscles cells (SMC) were studied. Twenty-four hours after adding
      insulin to SMC cultured medium, the B(max) was decreased by 18% when compared
      with the control (P<0.05). On the other hand, twenty-four hours after adding db
      cAMP to SMC cultured medium, the B(max) value was unchanged, but K(d) value was
      decreased 34% when compared with the control (P<0.001). The results suggested
      that insulin could induce the down regulation of the high density lipoprotein
      receptor and cAMP could promote HDL3 binding to SMC HDL receptor by increasing
      the affinity of the receptor in cultured human SMC.

PMID- 12219211
TI  - A Method of the Simultaneous Purification of Cardiac Troponin T and I.
AB  - A method of the simultaneous purification of cardiac troponin T (cTnT) and
      troponin I (cTnI) from human cardiac left ventricular muscle have been developed.
      Five mg cTnT and 10.2 mg of cTnI were obtained from 100 mg of cardiac muscle. The
      purity of cTnT and cTnI could reach to 97.6% and 97.2% respectively. Their
      immunoactivity and specificity have been identified by ELISA method.

PMID- 12219212
TI  - The Isolation of Carbohydrate-binding Peptide from Scarlet Runner Bean Lectin.
AB  - The carbohydrate-binding peptide fragment of scarlet runner bean (Phaseolus
      coccineus var. rubronanus) lectin has been prepared by trypsin digestion. The
      carbohydrate-binding peptide was isolated from digested solution by affinity
      chromatography on thyroglobulin-Sepharose column, Bio-Gel P-4 gel filtration
      column and reverse phase HPLC on C-8 column. The fraction of peak I from HPLC
      which bound specifically with Man(8)GlcNAc(2) was demonstrated by using dot blot
      technique with [(3)H]- Man(8)GlcNAc(2).

PMID- 12219213
TI  - Nucleotide Sequence Analysis of HaSNPV Protein Kinase.
AB  - The protein kinase gene of Helicoverpa armigera single nucleocapsid nuclear
      polyhedrosis virus (HaSNPV) has been cloned and sequenced. It is located
      approximately 1.25 kb downstream of the polyhedrin gene. The predicted molecular
      mass of this 267 amino acid protein (HavPK) is 31 kD. HavPK shows a 43.0% amino
      acid homology to vPK from Lymantria dispar multinucleocapsid nuclear polyhedrosis
      virus (LdMNPV) and a 39.0% homology to PK-1 from Autographa californica
      multinucleocapsid nuclear polyhedrosis virus (AcMNPV). Comparison of HavPK with
      protein kinases from other organisms showed that HavPK was also homologous to the
      catalytic domains of eukaryotic protein kinases and strongly indicated that HavPK
      was a serine/threonine protein kinase.

PMID- 12219214
TI  - Thermodynamic Stability of Hen Egg White Lysozyme and Its Mutants by Site
      directed Mutagenesis.
AB  - The folding transition thermodynamics parameters and activity of hen egg white
      lysozyme and its mutants, R21E, A31V, I55L, S91A, D101A, SIS, TIT, SVS, TVS by
      site-directed mutagenesis in urea solutions of various concentration were
      measured. The values of free energy of stabilization (delta G(T)(H(2)O)) are
      16.87-28.67 kJ/mol at 25 degrees, and those at midpoint of urea concentration for
      folding transition [C](1/2) are 4.89-6.24 M for the mutants, respectively. The
      possible folding transition mechanism in urea solution, the change of transition
      thermodynamic stability induced by site-directed mutagenesis, and the
      contribution of hydrophobic interaction and the volume change of amino acid
      residues to protein stability were discussed.

PMID- 12219215
TI  - Regulatory Effect of All-trans Retinoic Acid (ATRA) on the Activities of N
      acetylglucosaminyl Transferase (GnT) III, IV in HL-60 Cells.
AB  - The regulatory effect of all-trans retinoic acid (ATRA) on the activities of N
      acetylglucosaminyl transferase (GnT) III and IV in HL-60 Cells were studied. It
      was found that the activities of GnT-III and GnT-IV were significantly decreased
      by 0.1 &mgr;M ATRA, but not further decreased with the increase in concentration
      of ATRA to 1.0 or 10 &mgr;M. The activities of both GnT-III and GnT-IV in the
      untreated control cells were variable during the incubation of cells, showing a
      peak level at 24 h and 48 h in the un-synchronized culture and the synchronized
      culture respectively. After the treatment with ATRA, the peak value was still at
      24h in un-synchronized culture, and the activities of GnT-III and GnT-IV were
      gradually decreased only after 24 h of incubation both in un- synchronized and
      synchronized culture of HL-60 cells. The above results were discussed.

PMID- 12219216
TI  - Analysis of Activation Activity of Yeast PHO2, PHO4 Protein and Their
      Interaction.
AB  - Both PHO2 and PHO4 are positive regulatory factors of yeast PHO5 gene. Here we
      show that the PHO2 fused to yeast transcriptional factor GAL4 DNA-binding domain
      activates the expression of the reporter gene (lacZ), and the lacZ activities
      were regulated by Pi concentration, therefore it could be suggested that there
      are acidic activation domains on the PHO2 protein. Acidic amino acid rich region
      of 287-326 aa in PHO2 is not a transcriptional activation domain. PHO2 maintained
      its activation activity only if Ser230 is phosphorylated, thus the phosphorylated
      site may play a key role in the transcriptional activation function of PHO2. PHO4
      fused to the GAL4 DNA-binding domain also activates the expression of lacZ. A
      segment of 1-97 aa at its N-terminal is responsible for the transcriptional
      activation activity. A two-hybrid assay reveals that there exists interaction
      between PHO2 and PHO4 protein, and the interaction affects their transcriptional
      activation function.

PMID- 12219217
TI  - Secretory Expression of Porcine Insulin Precursor in Kluyveromyces lactis and Its
      Conversion into Human Insulin.
AB  - Porcine insulin precursor (PIP) was cloned to vectors derived from plasmid pKD1
      and expressed in Kluyveromyces lactis. The secretory expression level of PIP was
      20 to 30 mg per liter of the culture medium. Human insulin obtained from PIP
      through tryptic transpeptidation was characterized. Its amino acid composition,
      crystalline shape and biological activity are identical with those of native
      insulin.

PMID- 12219218
TI  - Expression of Cytosine Deaminase Gene in Human Colon Carcinoma Cells by
      Recombinant Retroviral Vector.
AB  - The recombinant retroviral vector pLCDSN containing E. coli cytosine deaminase
      gene was constructed. After packaging with PA317 cell line, the infectious
      particles were used to infect human colon carcinoma cell line LoVo. A single
      clone harbouring EC-CD gene was picked after G418 selection. There was no
      significant difference in cell growth curve or morphology between the LoVo/LCDSN
      and LoVo cells. Both of them were very sensitive to 5-FU in vitro (IC(50),
      approximately 0.5 &mgr;mol/L). However, the expression of the CD gene did
      increase the sensitivity of these cells to the nontoxic prodrug, 5-FC, decreasing
      the IC(50) for 5-FC from 22 000 &mgr;mol/L for parental LoVo cells to 13
      &mgr;mol/L for LoVo/LCDSN cells. Obvious by side effect was also observed. When
      cells transduced with CD gene were mixed with wild type cells at a ratio of
      30:70, above 80% of the cancer cells could be killed after treatment with a
      nontoxic concentration of 5-FC.

PMID- 12219219
TI  - Crystal Structure of Ca(2+) Ion-saturated Acidic Phospholipase A(2) From
      Agkistrodon halys Pallas.
AB  - The Ca(2+) ion is a cofactor for the catalysis of phospholipase A(2). The
      crystals of Ca(2+)-saturated acidic phospholipase A(2) from Agkistrodon halys
      Pallas were obtained by adding CaCl(2) during the crystallization to ensure the
      complete binding of Ca(2+). The synchrotron diffraction data were collected at
      1.6 Aring; resolution. The structure was determined by difference Fouriers
      methods. The refined structure of Ca(2+)-saturated acidicPLA(2) resembles closely
      that of the native acidicPLA(2) with, however, some small conformational
      differences in the Ca(2+)-binding site and the C-terminal loop. The pentagonal
      bipyramidal configuration consisting of seven oxygen ligands of Ca(2+) ion
      appears more regular than that of the native acidicPLA(2). The small
      conformational changes induced by Ca(2+) implies that the main role of Ca(2+) ion
      is to stabilize the oxyanion in the tetrahedral intermediate formed during the
      catalysis by electrophilic interaction.

PMID- 12219220
TI  - Interaction of Apolipoprotein Model Peptides with Liposomes: A High Performance
      Liquid Chromatography Study.
AB  - The apparent partition constants of two amphiphilic peptides, Amp1 and Amp2, for
      partitioning into phosphatidylglycerol/phosphatidylcholine bilayer were measured
      using size-exclusion high performance liquid chromatograph. The exposed amino
      groups of vesicle-bound peptides were studied by TNBS assay. It was proposed that
      their N-terminals were exposed to the aqueous phase, and that the main
      explanation for the stronger interaction of Amp1 with lipid bilayer compared with
      Amp2 was its stronger lipid binding ability, though Amp1 was also buried deeper
      in the lipid membrane. It was also found that the two peptides were polymerized
      in buffer, with their amino groups almost totally buried within the polymers.

PMID- 12219221
TI  - Expression of Chicken Smooth Muscle Myosin Light Chain Kinase in NIH 3T3 Cells.
AB  - The myosin light chain kinase (MLCK) is important in regulating the smooth muscle
      contraction. The pBKrsv-MLCK was obtained by inserting MLCK cDNA into pBKrsv
      polylinker and transfected into NIH 3T3 cells. The results revealed that the
      transfected cells can express chicken MLCK identified by DNA-PCR, RT-PCR and
      Western blot. The expressed MLCK has high activity, thus providing the basis for
      further investigation of the signal transduction and regulation of smooth muscle
      contraction of MLCK.

PMID- 12219223
TI  - Kinetic Properties of Choline Dehydrogenase.
AB  - The kinetic behavior of purified CDH had been investigated by steady-state
      initial velocity studies and inhibition studies with products. Variations in the
      concentration of one substrate led to changes in the K(m) and V(max) for the
      other substrate. The product betaine aldehyde was a noncompetitive inhibitor with
      respect to choline, whereas it competed with PMS. The results were consistent
      with a Bi-Bi Ping-Pong mechanism. 1-PC (1-pyrenebutyrylcholine bromide) and 9-AC
      (9-anthrolcholine bromide) behaved as mixed inhibitors, with K(i) values of 0.3
      mM and 3.67 mM respectively.

PMID- 12219222
TI  - Studies on the Relationship Between the Biological Activities and the Circular
      Dichroism of South Anhui Dienagkistrodon Acutus Hemorrhagins.
AB  - The solution conformations of three hemorrhagic toxins, designated as AaH I, AaH
      III and AaH IV, from South Anhui Dienagkistrodon acutus have been studied by CD
      spectra. The secondary structure of AaH I consisted of 25.8% alpha-helix, 12.7%
      beta-sheet and 26.8% beta-turns, together with 34.7% random coil. For AaH III,
      the secondary structure contents were 23.9%, 20.6%, 23.7% and 31.8%, and for AaH
      IV they were 18.2%, 31.0%, 17.2% and 33.8%, respectively. When pH was lower than
      4.0 or higher than 11.0, the alpha-helix decreased but beta-sheet increased,
      meanwhile, the caseinolytic activities of the three toxins decreased. The
      activities could be inhibited by EDTA, which indicated that all the three toxins
      were all metalloproteinases. EDTA, Cu(2+), Zn(2+), Ca(2+) and Mg(2+) could change
      the secondary structures and play an important role in caseinolytic activities.

PMID- 12219224
TI  - Purification and Characterization of a Novel 21 kD Calcium-binding Protein from
      Rabbit Appendix Lymphocytes.
AB  - A novel 21 kD calcium-binding protein from rabbit appendix B lymphocytes has been
      purified and characterized. Through heat-denaturation, using Phenyl-Sepharose and
      DEAE-Sepharose chromatography, we obtained 5.3 mg SDS-PAGE homogeneous CaBP(21)
      from 1 kg lymphocyte cells. Amino acid analysis showed the acidic amino acid
      content (Asp + Glu) to be 26% after HCL hydrolysis. The blocking of the N
      terminus of CaBP(21) prevents the de novo Edman degradation, like most of the
      other calcium-binding proteins. CaBP(21) has 46% of hydrophobic amino acid (with
      Gly, without Trp) content, 10% of basic amino acid content and 44% of acidic and
      polar amino acids. Peptide mapping and SDS-PAGE combined Sephadex G-25 gel
      filtration proves that CaBP(21) consists of two identical or similar subunits.
      Ca(2+)-binding assays using Arsenazo III indicated one protein to bind 4 Ca(2+)
      with dissociation constant (K(d)) for Ca(2+) about 10(-5) mol/L.

PMID- 12219225
TI  - Construction of Human Immunoglobulin Combinatorial Library and Screening of Phage
      Antibodies to Hepatitis B Surface Antigen.
AB  - Human immunoglobulin combinatorial library was generated by using phage surface
      display expression system, and phage antibodies (Fab fragments) to hepatitis B
      surface antigen (HbsAg) were screened from it. The products by half-nested PCR
      using signal peptide sequences as primers were superior in quality and quantity
      to those by PCR with conserved sequences in the 5'-end variable regions as
      primers. After three round of selections by biopanning, the ratio of positive
      clone was 69%. The inhibition assay showed the phage antibodies to be
      specifically anti-HbsAg. The V(H) genes were derived from V(H) I and V(H) III,
      while V(L)s belonged to V(lambda) II and V(lambda) I as shown by DNA sequencing.

PMID- 12219226
TI  - The Construction and Functional Study of Protein Kinase Inhibitor Phage.
AB  - A DNA fragment, which encoded the heat-stable protein kinase inhibitor (PKI) (5
      24) of camp-dependent protein kinase (cAPK), was synthesized and cloned into
      phage display vector fe-tet-DOG1. Thus, PKI(5-24) was displayed on the surface of
      phage fd, which was termed PKI phage (cAPK inhibitor phage), in a form fused with
      gene III protein (g3p). It was showed that PKI phage not only repressed cAPK
      effectively, but also bound with the immobilized recombinant His(6)-tag mouse
      cAPK-Calpha( His(6)-mCalpha) specifically. The bound PKI phages could be
      quantitatively eluted under acidic conditions. Model affinity screening
      demonstrated that PKI phages could be selectively enriched from the mixture of
      PKI phage and wild-type phages (1:10(8)) using affinity chromatography of
      immobilized His(6)-mCalpha. These results suggest that selecting protein kinase
      inhibitor by phage display technique is feasible.

PMID- 12219227
TI  - cDNA Sequences of Two Anti-mammals Neurotoxins from Scorpion Buthus martensii
      Karsch.
AB  - The total mRNA was prepared and purified from the venom gland of scorpion Buthus
      martensii Karsch (BmK). The cDNA library of this venom gland was then constructed
      using reverse transcription. Two cDNAs encoding the anti-mammalian neurotoxins,
      named as BmK M1 and BmK M9, were selectively amplified by PCR and sequenced. Both
      have open reading frames of 252 bp encoding 84 residues of the toxin precursors,
      including a 19 amino acid signal peptide, the mature toxin with 64 residues, and
      an additional Arg tail at the carboxyl-terminus which was removed during post
      protein processing. The deduced amino acid sequence of BmK M1 was completely
      identical with the known sequence of the natural toxin BmK M4, whereas the other
      BmK M9 shared a high homology with the natural toxin BmK M4, differing only in
      two residues. The cDNA of BmK M1 showed 87.2% homology with that of the African
      scorpion Lqh alphaIT.

PMID- 12219228
TI  - Studies on the Time-Resolved Polarized Fluorescence of R-Phycoerythrin Crystal
      from Red Alga Porphyra yezoensis.
AB  - The time-resolved polarized fluorescence of oriented R-phycoerythrin single
      crystal from red alga Porphyra yezoensis was studied in picosecond time scale.
      The fluorescence decay of the crystal exhibited two exponential processes, one of
      which was related to the energy transfer and excitation equilibrium between
      chromophores (tau(1)</=60 ps), and the other to the fluorescent transition of
      chromophores (tau(2) approximate, equals 300 ps). The fluorescence of the crystal
      was highly depolarized due to excitation transfer between chromophores, and its
      anisotropic decay was distinctly dependent upon the crystal orientation because
      of the distribution of chromophore optical transition moments predominantly
      orienting around the principal axis of the crystal.

PMID- 12219229
TI  - Studies on the Spectral Properties of Choline Dehydrogenase.
AB  - The addition of the substrate didn't show any influence on the intrinsic emission
      spectra of purified CDH, which had a maximum at 335 nm. On the other hand, the
      520 nm fluorescence of CDH increased after the addition of substrate. The
      secondary structure of solubilized CDH was examined by Fourier-transform infrared
      spectroscopy. The percentage distribution of its secondary structure assignment
      had been obtained: 53.4% alpha-helix, 24.5% beta-sheet, 13.9% 3(10)-helix and
      0.5% beta-turn. The predominant conformation of CDH was alpha-helix and beta
      sheet when there was no substrate. After the addition of substrate, the
      percentage of 3(10)-helix structure increased to 42%, whereas that of alpha-helix
      structure decreased to 35%, indicating that the conformation of CDH changed
      significantly after the binding of substrate of substrate to the enzyme.

PMID- 12219230
TI  - Studies on the Method for the Determination of beta1-4 Galactosyltransferase and
      Its Kinetics.
AB  - A fluorescence assay method for beta1-4galactosyltransferase (beta1-4GT) has been
      developed involving a pyridylaminated sugar as an acceptor substrate, a
      fluorescent sugar chain, with the reducing end of the Gnbeta1 - 2Malpha1 -
      6(Gnbeta1-2Malpha1-3)Mbeta1 - 4Gnbeta1 - 4Gn - PA aminated with 2-aminopyridine.
      Microsome was prepared from the liver of normal male rats as an enzyme sample.
      Then the fluorescent reaction product was separated by reverse-phase HPLC. The
      kinetic experiments were carried out using crude enzyme extracts of the Golgi
      complex from the rat liver. The enzyme has a pH optimum of 6.5,and optimal
      concentration of Triton X-100 of 0.5%. The K(m) and V(max) values for the sugar
      acceptor substrates were found to be 2.31x10(-3)M(-1) and 5.75x10(-2)
      &mgr;mol/(min.mg) respectively. Furthermore, our research revealed that beta1-4GT
      had branch specificity. The Gn of alpha1-3 mannose branch of the acceptor
      substrate was more susceptible to galactosylation than that of the alpha1-6
      branch by 2.10 times.

PMID- 12219231
TI  - Interaction of the Apolipoprotein A-I Model Peptides with Liposomes.
AB  - Two amphiphilic peptides, Amp1 and Amp2, were synthesized according to the
      sequence of the lipid-binding domain in apolipoprotein. Amp2 has a Val residue
      substituted for the Lys at the 4th position of Amp1. Intrinsic fluorescence
      spectra, peptide-induced leakage of calcein-laoded liposomes, quenching of
      tryptophan fluorescene by iodide and acrylamide, circular dichroism spectra, and
      measurement of the membrane penetration depth of tryptophan residue with spin
      labeled phospholipids indicate unexceptionally that Amp1 interacted more strongly
      with the lipid bilayer than Amp2. It is proposed that class A amphiphilic alpha
      helix is buried in the membrane in such a way that its long axis is oriented
      parallel to the membrane plane, and the electrostatic interaction between the
      positively charged residues located at the polar-nonpolar interface of the
      amphiphilic helix with the negatively charged head groups of phospholipids is
      important to the lipid affinity of the amphiphilic peptide.

PMID- 12219233
TI  - Detecting Repetitive DNA in Eukaryotes.
AB  - A detection software of repetitive elements, especially for Alu is designed
      according to the theory of the correspondence analysis. The results obtained on
      the test set of 38 gene sequences showed that the true-negative is about 5.8% and
      false-positive is about 4.8%. Also, the detailed description of Alu elements in
      the sequences in which the Alu elements are spliced into coding-regions and the
      successful search for Alu in large-scale T-cell receptor loci sequence showed
      that the software is a better tool for the recognition of repeat elements.

PMID- 12219232
TI  - Expression of the Arrowhead Proteinase Inhibitor B (API) Gene in the Silkworm
      Larvae and Pupae.
AB  - The arrowhead proteinase inhibitor B (API) gene was cloned into baculovirus
      transfer vectors of pBacPAK8 and pOSX, and two recombinant transfer vectors,
      pBacPAK (API) and pOSX (API), were constructed. Co-infection was accomplished
      with either one of the recombinant transfer vectors and Bm-BacPAK6 DNA in BmN
      cells. Then recombinant virus of CrBK9, CrBK10 and BX was selected. API gene was
      successfully expressed in silkworm larvae and pupae. The recombinant API (rAPI)
      showed strong inhibitive activity on bovine pancreas trypsin. The inhibiting
      activity of the expression product was 1.0x10(5) u/ml haemolymph for silkworm
      larvae and 1.3x10(5)u/ml haemolymph for pupae. In addition, SDS-PAGE of the
      preliminarily purified rAPI showed its molecular weight to be about 19 kD.

PMID- 12219234
TI  - Studies on the Expression of the 28 kD Glutathione S-transferase Gene from
      Schistosoma japonicum in the Silkworm (Bombyx mori) Larvae and Insect Cells.
AB  - The gene of the 28 kD glutathione S-transferase (GST) from the Chinese strain of
      Schistosoma japonicum had been expressed in the silkworm (Bombyx mori) cells and
      larvae by Bombyx mori nuclear polyhedrosis virus (BmNPV) vector which had been
      modified. The GST gene was inserted into the right position of the BmNPV genome
      as identified by Southern hybridization. The product was a 28 kD protein, had GST
      activity and antigenicity. The yield in BmN cells (1x10(6) cells/ml) was 0.77 mg
      and more than 5 mg in a silkworm larvae. All the results showed that it is
      possible to develop the GST expressed in the silkworm larvae to a new kind of
      genetic engineered schistosomiasis vaccine.

PMID- 12219235
TI  - The Involvement of Ferredoxin-NADP Reductase in the Photosynthetic Cyclic
      Electron Transport.
AB  - As an inhibitor of ferredoxin-NADP reductase (FNR), heparin strongly inhibited
      the Fd-mediated photoreduction of NADP in spinach thylakoids at very low
      concentration (micromole), and also inhibited the delayed light emission induced
      by Fd/NADP. Under anaerobic conditions, when DCMU was present to block electron
      transfer from photosystem II, the Fd-mediated cyclic electron transport around
      photosystem I as indicated by the quenching of 9-aminoacridine can be measured.
      Heparin could strongly inhibit this cycle, but had no significant effect on the
      PMS-mediated cyclic electron transport around photosystem I. Heparin did not
      inhibit the electron transport from phototsystem I to ferredoxin, which was
      demonstrated by measuring the photoreduction of ferredoxin. The above results
      indicate that heparin inhibits ferredoxin-mediated cyclic electron transport by
      inhibiting the activity of FNR, and support the hypothesis of the involvement of
      FNR in cyclic electron transport.

PMID- 12219236
TI  - The Characteristics of DCPIPH(2) right curved arrow MV Electron Transport in Rb.
      sphaeroides 601.
AB  - The absorption spectrum and fluorescence emission spectrum of RS601 were found to
      keep the typical characteristics of those of the purple nonsulfide bacteria Rb.
      sphaeroides. Under illumination, methyl viologen was reduced by RS601
      chromatophores in the presence of DCPIPH(2) as the electron donor, setting up a
      standard noncyclic electron transport. o-phenanthroline with I(50) of 1.0 mM
      inhibited the DCPIPH(2) right curved arrow MV electron transport. Antimycin A did
      not inhibit the DCPIPH(2) right curved arrow MV electron transport and had no
      I(50). The results suggested that the exact site where methyl viologen accepted
      electron should locate between the secondary electron acceptor, Q(B), and cyt b,
      but not at the Q(A) binding site as indicated before. The difference of electron
      transport between reduced sides of reaction centers of Rb. sphaeroides and Rs.
      rubrum was discussed.

PMID- 12219237
TI  - Comparison of Different Effects of Chloroacetates on Electron Transports in PS II
      and in the Reaction Center of Rb. sphaeroides 601.
AB  - Chloroacetates displayed different effects on electron transports in the
      photosynthetic reaction center of purple bacteria (Rb.sphaeroides 601) and in the
      photosystem II (PS II) of higher plants. Decays of chlorophyII a fluorescence
      measured after actinic flashes show that chloroacetates inhibit the electron
      transport from Q(A)(-) to Q(B) (Q(B)(-)) and the equilibrium between Q(A)(-)Q(B)
      (Q(B)(-)) and Q(A)Q(B)(-) (Q(B)(2-)), acting on electron transport as well as
      proton transduction. The study on PSII electron transport indicates another
      inhibition site of chloroacetate at the oxidation side of PSII. Chloroacetates up
      to 500 mM have no inhibition on the DCPIPH(2) right curved arrow MV electron
      transport in the RS601's chromatophores. Dissociation constants of OP and
      trichloroacetates from RS601 reaction center were assessed to be 1.1x10(-3) M and
      from Dixon curve respectively. The differences on aspects of structures and
      functions between RS601 reaction center and PS II were discussed.

PMID- 12219238
TI  - Influence of Substrate and Ribozyme Sequences on the Functions of Ribozyme.
AB  - The mono-component ribozyme RZ1, RZ3 and RZ4 were ligated in different orders
      into two tri-component ribozymes RZ134 and RZ413.Both tri-component ribozymes
      could cleave individual specific substrate sequences from different regions of
      the tobacco mosaic virus (TMV) RNA. The cleavage efficiency and specificity of
      each unit-ribozymes in the tri-component ribozymes to its substrate was similar
      to its mono-ribozyme counterpart. When the three substrates were mixed and used
      as substrates for the tri-component ribozymes, only the activity of the unit
      ribozymes RZ4 was clearly observed, the activities of the other two unit
      ribozymes were greatly reduced. The reduction was mainly due to the fact that the
      two substrates BT2(+) and BT2(-) for RZ1 and RZ3 were complementary in sequence
      to each other and therefore formed duplex in the target region, thus must have
      strongly prevented the two ribozymes from forming the correct structures required
      for cleavage activity. In addition to its activity on the substrate BT2(+), the
      ribozyme RZ1 was found unexpectedly to be able to cleave BT4(-) specifically into
      various unique products.

PMID- 12219239
TI  - Cloning of the K. fragilis PDI Gene.
AB  - The K. fragilis CBS 397 gene library was screened by the PDI probe, which was
      designed according to the homology with the S. cerevisiae PDI gene. One positive
      clone was found and confirmed. In order to learn its physical map,Southern
      hybridization was done on this positive clone. The K. fragilis PDI gene was found
      to locate in chromosome V genome. Its sequence was also made partly known by DNA
      sequencing. From the method of the turbidimetric assay of insulin disulfide
      reduction, we have also demonstrated that the cloned PDI gene can exhibit PDI
      activity.

PMID- 12219240
TI  - Effects of the N-salicylaladehyde Aminoglucose Schiff Base Complexes no O(2)(-).
      and DNA.
AB  - The effects of SG schiff base complexes with Cu(II), Zn(II), Co(III) on O(2)(-).
      and DNA were studied. The results showed that both CuSG and ZnSG could an inhibit
      the synthesis of O(2)(-). markedly. The inhibiting effect of CuSG was larger than
      that of ZnSG. Complexes CuSG and CoSG could also combine with the salmon sperm
      DNA. The intrinsic association constant (K(0)) for CuSG and CoSG were estimated
      to be 2.86x10(4) M(-1 and 1.29x105) M-1 respectively. The numbers of binding
      sites per 100 nucleotide (n) were 2.5 and 7.5 respectively.

PMID- 12219241
TI  - Studies on the Denaturation and Conformation of Choline Dehydrogenase.
AB  - The substrate choline was able to improve the pH stability of choline
      dehydrogenase (CDH). It was found that during the thermal denaturation there were
      an increase of beta-structure and a decrease of the alpha-helix content. Changes
      in beta-structure were attributed to beta-turn and 3(10)-helix. The substrate had
      a protective effect on CDH thermal denaturation. The proportion of 3(10)-helix
      content of the SDS-denatured protein and that in the presence of substrate was
      33% and 31.2% respectively; while, the corresponding proportion of beta-sheet was
      29% and 10.6%, respectively. Moreover, when the absorption proportion of alpha
      helix, random coil and the side-chain of tyrosine residues were concerned, it was
      found that the spectral property of the CDH treated by denaturants in the
      presence of substrate were rather similar to that of the non-denatured enzyme.

PMID- 12219242
TI  - An Assay System for the Growth Promoting Activity of Insulin by (3)H-thymidine
      Incorporation.
AB  - In a chemically defined serum-free medium, insulin can stimulate DNA synthesis of
      the mouse mammary tumor-derived cell line GR2H6 up to 3 - 5 fold above the
      control group as measured by (3)H-thymidine incorporation. By growing GR2H6 cells
      in the 24-well and 96-well plates, a bioassay system for the growth promoting
      activity of insulin has been established. This method has the advantages such as
      easy operation, less time-consuming and suitable for measuring a large number of
      samples simultaneously. It may provide a novel model system for studies on the
      relationships between the growth promoting activity and the structure of insulin.

PMID- 12219243
TI  - Function of the Hydroxyl Radical in Bleomycin A(5)-induced DNA Degradation.
AB  - The production of.OH in the mixture of BLMA(5), Fe(2+) and O(2) has been detected
      by ESR spectroscopy and the degradation of DNA induced by BLMA(5), in the
      presence of Fe(2+) and O(2), has been detected by TBA reaction. When Fe(2+) was
      replaced by Cu(+), Cu(2+) or Fe(3+),.OH was not producted and DNA not degraded.OH
      scavenger could scavenge.OH effectly but had little effect on the DNA
      degradation. Reducing agents could scavenge.OH but enhanced the DNA degradation.
      SOD could scavenge.OH but inactivated SOD showed no effect on.OH. Both SOD and
      inactivated SOD could inhibit the degradation of DNA.OH reacted more readily with
      bases than with deoxyribose, while the main injury of DNA induced by BLMA(5) was
      the destruction of deoxyribose. The results suggest that.OH was generated in the
      mixture of BLMA(5), Fe(2+) and O(2) but not the key factor which initiated the
      degradation of DNA. It could be the activated BLMA(5).Fe(2+).O(2) complex that
      induced the degradation of DNA.

PMID- 12219244
TI  - Construction and Physical Mapping of the 35 cM YAC Contigs for the Region of
      Xp11.2 - p21.3.
AB  - One hundred and fifty-one YACs were selected from three libraries with a series
      of STS and other DNA probes of the human X chromosome p11.2 - p21.3 region. The
      YAC contigs, spanning about 35cM in all and generally cover the whole region,
      were constructed based on the physical analysis of the positive clones. A total
      of seventy-seven DNA markers of this region were located and ordered on this map
      with an average 454 kb spacing, in which fifty-three were polymorphic markers
      with an average 0.6 cM genetic spacing. These results facilitate the search for
      novel genes and the sequence analysis of this region.

PMID- 12219245
TI  - Expression of Anti-PCNA mRNA Ribozyme by T7 Vaccinia Virus System in HeLa Cells.
AB  - We have designed and synthesized a hammer-head Rz targeted to human proliferating
      cell nuclear antigen (PCNA) mRNA at site No.524. Results showed that Rz524 can
      cleave the transcribed substrate RNA site-specifically in vitro. A self trimming
      expression plasmid of this Rz was constructed and co-introduced into HeLa cells
      with T7 vaccinia virus. Dot-blotting hybridization showed that the Rz was
      expressed in HeLa cells.

PMID- 12219246
TI  - Development and characterization of rosin-based polymer and its application as a
      cream base.
AB  - The literature contains many references to the wide range of uses of rosin-based
      polymers, but little has appeared in the area of rosin-based polymers used as
      cream bases. Various rosin polymers based on glycerol, sorbitol, and
      pentaerythritol were prepared and screened for efficacy as cream bases. Among
      these polymers, polymer 2 (glycerol-based) is reported in the present study as it
      produced creams with a better stability and release profile as compared to other
      creams. The creams were formulated employing polymer 2 (P2) and Tween 60 as
      surfactants. The stability of the prepared creams, as well as the diclofenac
      diethylammonium release pattern, was investigated using particle size analysis,
      conductivity, relative dielectric constant, spreadability, and irritation
      potential measurement, and was compared with that of creams containing Tween 60
      (RT) prepared in the laboratory. The release of the drug, diclofenac
      diethylammonium, was measured after eight hours and compared with a standard
      cream (RT) and a marketed cream (RM).

PMID- 12219247
TI  - An in vitro, ex vivo, and in vivo demonstration of the lipolytic effect of
      slimming liposomes: An unexpected alpha(2)-adrenergic antagonism.
AB  - Most of the slimming products already developed for cosmetic applications did not
      result from strategies that integrate whole lipolysis-regulating mechanisms. We
      thus focused our attention on a more complete integration of these mechanisms and
      we developed slimming liposomes (SLC) containing two micro-circulation
      activators, i.e., esculoside and Centella asiatica extracts, one
      phosphodiesterase inhibitor, i.e., caffeine, and one fatty acid-beta oxidation
      activator, i.e., L-carnitine. The validity of our approach was assessed through
      (a) in vitro tests demonstrating that SLC induced a dramatic increase in the
      cyclic adenosine monophosphate (cAMP) content in human adipocytes, with a
      subsequent rise in the nonesterified fatty acids (NEFA) content of human
      adipocyte incubation medium, and (b) in vivo studies showing that SLC could
      provide an actual potent slimming effect on human volunteers. Moreover, we give
      here, through binding experiments, the unambiguous demonstration that SLC is able
      to antagonize the alpha(2)-adrenergic receptor that is known to reduce
      intracellular AMPc content and, subsequently, to down-regulate lipolysis. This
      alpha(2)-adrenergic antagonism has never been reported for any component of SLC,
      and this work is the first demonstration of the alpha(2)-adrenergic antagonism of
      such a combination of active liposome compounds.

PMID- 12219248
TI  - Investigations of cosmetically treated human hair by differential scanning
      calorimetry in water.
AB  - By applying differential scanning calorimetry (DSC) on human hair in water, the
      thermal stability of hair' major morphological components is determined. Against
      the background of the two-phase model for alpha-keratins, these components are
      identified as the partially helical, fibrous intermediate filaments (IF) and the
      intermediate filament associated-proteins (IFAP) as a cross-linked, amorphous
      matrix. DSC yields the denaturation enthalpy deltaH(D), which depends on the
      amount and structural integrity of the alpha-helical material, and the
      temperature T(D), which is kinetically controlled by the cross-link density of
      the matrix. To assess the effects of cosmetic treatments, hairs were investigated
      that had undergone either multiple bleaching or perm-waving treatments. The
      respective dependencies between denaturation temperature and enthalpy show that
      both morphological components are similarly affected by bleaching, while
      reductive damage, in comparison, is more pronounced in the IFs. For both types of
      treatments, changes in enthalpy follow apparent first-order kinetics with respect
      to the number of treatments as well as treatment time (perm-waving), yielding
      characteristic reaction rate constants. It appears that DSC in water is an
      especially suitable method to determine the kinetics of damage formation in human
      hair resulting from cosmetic treatments.

PMID- 12219249
TI  - Glycerin (glycerol): Current insights into the functional properties of a classic
      cosmetic raw material.

PMID- 12219250
TI  - A test for antioxidant activity in cosmetic formulations.
AB  - The aim of this study was to develop a technique to assay for the activity of
      antioxidants in a finished cosmetic product. This was accomplished by adapting
      the Randox Assay for Total Antioxidant Status kit so that diluted samples could
      be evaluated by kinetic as well as end-point determinations. Using this
      technique, we found that a finished product had an IC(50) of 0.07 gm of product
      and a relative antioxidant activity concentration of 52.7 nmoles/mg.

PMID- 12219252
TI  - Long-term safety of spironolactone in acne: results of an 8-year followup study.
AB  - BACKGROUND: Spironolactone has been used for over 20 years as an antiandrogen in
      the treatment of acne and hirsutism. No long-term studies of the safety of
      spironolactone used in this manner have been published. We present a study of the
      long-term safety and tolerance of spironolactone in 91 women with acne who were
      followed for up to 8 years. METHODS: A survey questionnaire was sent to 210
      patients, and a comparison chart review of all patients to whom the survey was
      sent was made. RESULTS: Ninety-one completed surveys were analyzed, comprising
      506 person-years of followup and 200 person-years of spironolactone exposure.
      Mean treatment length was 28.5 months (range = 0.5-122 months). During the 8-year
      followup period, there were no cases of serious illness attributable to
      spironolactone use. Side effects were present in 59% and resulted in cessation of
      the drug in 15%. Diuretic effect and menstrual irregularities were the most
      common adverse effects. CONCLUSIONS: After 200 person-years of exposure to
      spironolactone and 506 person-years of followup over 8 years, no serious
      illnesses thought to be attributed to spironolactone were reported. The long-term
      use of spironolactone in the treatment of acne in women appears to be safe. Side
      effects, however, are common, although not usually a cause for stopping the drug.

PMID- 12219253
TI  - Preoperative risk stratification using electron beam computed tomography in
      elective vascular surgery: relationship to clinical risk prediction and
      postoperative complications.
AB  - We studied the utility of electron beam computed tomography as a screening test
      for the cardiovascular risk of elective vascular surgery. In 45 patients
      undergoing principally carotid and aortic surgical procedures, coronary artery
      calcification was prevalent and severe, and related to the clinically predicted
      cardiovascular risk of the procedure. However, only the clinically predicted
      surgical risk, and not coronary artery calcification, was related to the
      incidence of perioperative cardiovascular complications.

PMID- 12219254
TI  - [The role of myocilin in the pathogenesis of primary open-angle glaucoma].
AB  - Mutations in myocilin are responsible for autosomal-dominant inherited juvenile
      open-angle glaucoma and some subgroups of adult-onset glaucoma (POAG). Myocilin
      is a secreted glycoprotein with a molecular weight of approximately 55-57 kDa
      that forms dimers and multimers. Structural motives are domains that have
      similarities with myosin and olfactomedin, a signalling sequence as well as a
      leucine zipper at the N-terminus of myocilin. Most mutations that were identified
      in patients with POAG are localized in the olfactomedin domain which is highly
      conserved between species. In the eye, myocilin is highly expressed in the
      trabecular meshwork (TM), the sclera, the ciliary body and the iris, lower
      amounts are seen in the retina and the optic nerve. In addition, secreted
      myocilin is detected in the aqueous humor. In the chamber angle, myocilin is
      associated with fibrillar components of the extracellular matrix in the
      cribriform portion of the TM. Myocilin binds specifically to the HepII domain of
      fibronectin. In organ cultures of perfused anterior eye segments, recombinant
      myocilin increases outflow resistance. In cultured TM cells, myocilin is induced
      by treatment with dexamethasone in a similar time course as observed in steroid
      induced glaucoma. Myocilin is also induced by transforming growth factor-beta
      (TGF-beta) and mechanical stress. Mice with a targeted disruption of the myocilin
      gene do not express a phenotype. Experimental data indicate that mutated myocilin
      is not secreted and accumulates in cells which might critically impair the
      function of the TM.

PMID- 12219255
TI  - [Control of wound healing after glaucoma surgery. Effect and inhibition of the
      growth factor TGF-beta].
AB  - The main problem of the surgical failure after trabeculectomy is postoperative
      scarring of the filtering bleb. The treatment with anti-metabolites such as 5
      fluorouracil and mitomycin C to prevent scarring shows many toxic side-effects
      and causes patient stress. In the search for therapeutic alternatives, the focus
      of current research concentrates on the pathophysiological interaction between
      growth factors and their role in the induction of scarring. Among the growth
      factors, TGF-beta 2 represents an important stimulant of scarring with a key
      regulatory function. The TGF-beta 2 concentration in the aqueous humor of primary
      open angle glaucoma is significantly elevated. In vitro and in vivo studies have
      demonstrated promising inhibition of scarring after subconjunctival application
      of human monoclonal anti-TGF-beta 2 antibody, which appears to be a safe and well
      tolerated therapeutic approach. Currently, several prospective studies are
      investigating the role of anti-TGF-beta 2 antibody as an alternative to
      conventional long term inhibition of scarring.

PMID- 12219256
TI  - [Relevance of the pseudoexfoliation syndrome for the glaucomas].
AB  - Secondary chronic open-angle glaucoma associated with pseudoexfoliation (PEX)
      syndrome accounts for approximately 25% of all glaucomas and represents the most
      common identifiable cause of glaucoma overall. The underlying disorder, PEX
      syndrome, is a generalized process of the extracellular matrix characterized by
      production and progressive accumulation of an abnormal extracellular material in
      many intra- and extraocular tissues. Recent data support the pathogenetic concept
      of PEX syndrome as a type of elastosis affecting particularly elastic
      microfibrils. Active involvement of the trabecular meshwork in this
      characteristic matrix process may lead to glaucoma development in 40-60% of the
      patients. In addition, PEX syndrome also represents an important risk factor for
      a broad spectrum of spontaneous or intra- and postoperative ocular complications
      as well as for systemic cardiovascular diseases. PEX-associated open-angle
      glaucoma represents a relatively severe and progressive type of glaucoma with a
      generally poor prognosis due to high intraocular pressure levels and fluctuations
      in the diurnal pressure curve. The primary cause of chronic pressure elevation
      appears to be local production of PEX material by trabecular meshwork cells and
      Schlemm's canal cells with subsequent degenerative changes of Schlemm's canal and
      juxtacanalicular tissues. Additional pathogenetic factors contributing to
      pressure increase include pronounced melanin dispersion, increased protein
      concentrations of the aqueous humor, vascular factors, and connective tissue
      alterations of the lamina cribrosa. Other types of glaucoma, such as acute open
      angle glaucoma, provoked by melanin showers during diagnostic mydriasis, or
      secondary angle closure glaucoma due to pupillary or ciliary block, are also
      common in PEX patients. The pathogenetic factors TGF-beta1 and TIMP-1/2 appear to
      be causally involved in this fibrotic process and thus may represent potential
      targets for specific, rational therapeutic approaches.

PMID- 12219257
TI  - [Efficiency of mycophenolate mofetil in the treatment of intermediate and
      posterior uveitis].
AB  - BACKGROUND: The severity of disease and the side-effects of long-term
      corticosteroid treatment support the rationale for other immunosuppressive drugs
      in the management of uveitis. Mycophenolate mofetil (MMF) is a selective
      inhibitor of ionosine monophosphate dehydrogenase and exerts its major effects by
      modulation of the function of T and B lymphocytes. This study was undertaken to
      evaluate the clinical effect of MMF in the control of intermediate and posterior
      uveitis. METHODS: A retrospective study of 18 consecutive patients with
      intermediate or posterior uveitis treated with MMF was performed. Activity of
      intraocular inflammation was graded according to the guidelines of the
      international uveitis study group before and during treatment with MMF.
      Furthermore, the ability of MMF treatment to reduce the steroid dosage and/or
      substitute other immunosuppressive agents with unacceptable side-effects
      (cyclosporin A, tacrolimus, azathioprine) was evaluated. RESULTS: The indication
      for treatment with MMF in all 18 patients (age range: 11-73 years) was either
      poor control of ocular inflammation by the previous immunosuppressive therapy or
      unacceptable side-effects of this therapy. The daily MMF dose was 2 g and therapy
      was combined with cyclosporin A and/or prednisolone. One patient received MMF
      monotherapy. Corticosteroids were discontinued in 4 patients and the steroid dose
      could be reduced in 14 patients following MMF therapy. Marked resolution of
      ocular inflammatory activity occurred in 13 patients. The most frequently
      observed side-effects of MMF were myalgia, fatigue, headache and gastrointestinal
      problems. CONCLUSION: MMF was effective in disease control in the majority of
      patients with intermediate and posterior uveitis and proved to be a useful second
      line immunosuppressant for refractory intraocular inflammatory disease with an
      acceptable profile of side-effects.

PMID- 12219258
TI  - [Diagnosis of retinal diseases. Comparison between multifocal ERG and fundus
      perimetry - a case study].
AB  - BACKGROUND: There are new methods available for function testing of the macula,
      i.e. multifocal Electroretinography (mfERG) as well as fundus perimetry with the
      scanning laser ophthalmoscope (SLO). The value and clinical impact of these
      methods have still to be evaluated. We wanted to compare the results from
      patients having undergone both examinations. PATIENTS AND METHODS: A total of 33
      eyes from 25 patients (visual acuity 0.03-0.8) aged 14-79 years were examined
      using fundus perimetry with the SLO. In addition, multifocal ERG was performed in
      all eyes, where 61 local ERGs inside the 30 degrees visual field were recorded.
      We compared the depth of the scotoma with the reduction of the amplitudes during
      mfERG taking the fixation status into consideration. RESULTS: Examination time
      was comparable for both examination techniques. There was good concordance for
      eyes with retinitis pigmentosa with only central response. In contrast, patients
      with juvenile macular dystrophy demonstrated different results with comparable
      size of the defect while sometimes an enlarged pathology during mfERG was
      observed. Correlation between pathology findings observed in mfERG and fundus
      changes was difficult due to the change of the point of fixation caused by
      central scotoma. In age-related macular degeneration correlation of the findings
      was less obvious. DISCUSSION: The different setting with supra-threshold stimuli
      during ERG in contrast to near-threshold stimulus presentation during perimetry,
      might be the reason for differences even in the beginning of retinal diseases. In
      addition, reduced stability of fixation leads to artifacts during mfERG while it
      may be compensated for in fundus perimetry. Both methods are of additional value
      and demonstrate different results depending on the disease.

PMID- 12219260
TI  - [Relationship between lens power in refraction].
AB  - BACKGROUND: To achieve emmetropia, several components such as the cornea and lens
      power, and axial length have to be coordinated. Until now, not much is known
      about the influence of these factors on each other. METHODS: A total of 66
      healthy subjects were enrolled in this study. Ocular dimensions including
      anterior chamber depth, lens thickness, vitreous chamber depth, and axial length
      were measured by A-scan ultrasonography. Corneal radius and corneal refractive
      power were determined by ophthalmometry. The equivalent lens power was calculated
      by a method based on the Gullstrand schematic eye. RESULTS: As expected, a good
      correlation was found to exist between refraction and axial length. Lens power
      was independent of refraction, but in emmetropic eyes a good correlation between
      lens power and axial length could be found. Higher axial length was related to
      lower values of lens power and vice versa. CONCLUSION: In emmetropic eyes,
      deviation of axial length seems to be compensated by lens power and if this
      mechanism does not function, ametropia results.

PMID- 12219259
TI  - [Phototherapeutic keratectomy for recurrent corneal erosion syndrome (e-PTK).
      Report on 116 consecutive interventions].
AB  - BACKGROUND AND AIMS: Patients with recurrent corneal erosion syndrome can suffer
      both psychologically and socially due to excessive pain. After the failure of
      conservative treatment, conventional surgical interventions, such as anterior
      stromal puncture have been suggested. The purpose of this study was to assess the
      morphological and functional results of minimally invasive excimer laser
      phototherapeutic keratectomy (e-PTK) for treatment of recurrent corneal erosion
      syndrome and in particular, to evaluate the cumulative recurrence rate. PATIENTS
      AND METHODS: Between July 1990 and January 2001, 116 e-PTKs have been performed
      mostly in the acute stage of the disease in this single center study. In 15 eyes
      an unsuccessful PTK had previously been performed elsewhere. Reasons for the
      erosion included trauma ( n=80), Cogan's epithelial dystrophy ( n=14), bullous
      keratopathy ( n=2), and in 20 cases no cause could be detected. A manually guided
      spot profile was applied in 99 cases (pulse energy 10 mJ, repetition rate 2/s or
      3/s, 66-330 pulses). In 17 cases a scanning slit procedure was applied (intended
      ablation per scan 1 microm, repetition rate 20/s, 447-1,017 pulses). The broad
      deepithelialisation of Bowman's layer was treated with defocussed overlapping
      laser pulses. RESULTS: Complete epithelial closure was achieved after an average
      of 2.3+/-1.3 (median 2) days, the mean follow-up was 2.2+/-1.6 years with a
      maximum of 5.6 years. Best corrected visual acuity increased from 0.6+/-0.4
      preoperatively to 0.9+/-0.3 postoperatively. The keratometric central power
      remained constant (preoperative 43.0+/-2.2 D (diopters), postoperative 43.3+/-1.9
      D). The median keratometric astigmatism remained constant at 1.0 D. Only in 2
      patients was an iatrogenic, not completely reversible irregular astigmatism of
      more than 2 D induced during the learning curve. The spherical equivalent did not
      change significantly (-1.0+/-3.3 D preop., -1.1+/-3.4 D postop.). In 9 eyes
      (7.8%) a recurrent epithelial defect occurred after 2-24 (average 8+/-6) months.
      The cumulative 1-year recurrence rate was 6.5%, the 2-year recurrence rate was
      11.5%, the 3-, 4-, and 5-year recurrence rates were all 13.6%. CONCLUSIONS: For
      recurrent corneal erosion syndrome, e-PTK performed with low pulse energy and low
      number of pulses can be considered an effective treatment modality to achieve a
      fast and mostly durable epithelial closure. Even after broad removal of the loose
      epithelium, change of refraction or induction of an irregular astigmatism with
      visual loss seems to be the exception.

PMID- 12219261
TI  - [The reproducibility of multifocal ERG recordings].
AB  - PROBLEM: Multifocal electroretinogram recordings (mfERG) can be used to detect a
      local dysfunction of the retina. In this study we tested both the intrasessional
      and inter-sessional reproducibility of mfERG amplitudes. METHODS: MfERGs from 6
      eyes of 6 normal subjects were recorded on two different days using DTL
      electrodes. The relative coefficient of variation ( RCV) was used to quantify the
      amplitude reproducibility. We tested the effect of (a) session (inter- vs.
      intrasessional), (b) recording duration (7.3 vs. 3.6 min), (c) trace type
      (hexagon traces vs. ring averages), and (d) amplitude definition (peak-trough
      analysis vs. scalar product) on RCV. RESULTS: RCV was 6.5+/-0.4% (Mean+/-SEM,
      n=96) when averaged across all recording conditions and all subjects. The ANOVA
      showed a significant difference ( p=0.018) between hexagon traces and ring
      averages. Another significant effect ( p=0.016) occurred for the interaction of
      (a) and (b). CONCLUSION: MfERGs can be recorded with a high degree of
      reproducibility even for short recording durations and single hexagon traces. As
      the factor (a) did not show a significant effect, the new placement of the DTL
      electrode in the second session does not necessarily increase the retest
      variability compared to a second recording within the same session.

PMID- 12219262
TI  - [Follow-up on MEWDS by fundus perimetry and multifocal ERG with the SLO].
AB  - BACKGROUND: Most conventional techniques for examination such as perimetry or ERG
      may not be sensitive enough to detect functional alterations due to MEWDS
      precisely. We report on a follow-up performed by fundus perimetry and the new
      technique of multifocal ERG using the scanning laser ophthalmoscope. PATIENT AND
      METHOD: A 24-year-old female patient (VA 0.2/0.8) was followed up for 7 weeks
      with these techniques as well as Octopus perimetry, fluorescence angiography,
      Ganzfeld ERG and biomicroscopy. Multifocal ERG stimulation (mfERG, Retiscan) was
      performed with the SLO. RESULTS: Visual acuity improved from 0.2 to 0.8 and the
      central relative scotoma disappeared while a relevant increase of P1-wave
      amplitudes in mfERG could be observed. CONCLUSION: Combining objective
      measurements from the fundus controlled SLO-mfERG and results from fundus
      perimetry enable good correlation of morphology and results, even for minor
      alterations of the macula only accessible by few established clinical
      examinations.

PMID- 12219263
TI  - [Side-effects and risk profile of latanoprost 0.005% (Xalatan)].
AB  - BACKGROUND: Latanoprost, a prostaglandin F(2alpha)-analogue, has been widely in
      use in clinical practice for a period of over 5 years. The side-effects of
      latanoprost are analyzed and the clinical relevance is discussed. RESULTS:
      Hypertrichosis and increased pigmentation of eyelashes will develop in the
      majority of patients using latanoprost for more than 6 months. Increased
      pigmentation of the eyelids may also occur. Hyperpigmentation of the iris is seen
      in 12-18% of caucasians using latanoprost over a period of 1-2 years. Increased
      iris pigmentation seems more common in asian people and remains unchanged after
      discontinuation of therapy. Pigmentation of intra- and extraocular structures is
      caused by increased melanogenesis, not by melanocyte proliferation. Mild
      conjunctival hyperemia may develop in approximately 30% of patients, but is most
      often without clinical relevance. Further reported side-effects include anterior
      uveitis, reactivation of herpes-keratitis/-dermatitis and cystoid macular edema
      in pseudophakic and aphakic patients. A causal relationship has still not been
      proven for these side-effects. Systemic side-effects are rare (e.g. headache,
      facial rash, cardiovascular effects). No experience exists for treatment of
      glaucoma with latanoprost in childhood. CONCLUSION: Latanoprost represents a
      highly effective antiglaucomatous drug, rarely associated with vision-threatening
      complications. The most common complications are hypertrichosis of eyelashes and
      increased pigmentation of extra- and intraocular structures. A careful lifetime
      evaluation of these patients is recommended. Systemic side-effects are rare, but
      may occur.

PMID- 12219264
TI  - Exoenzymatic activity and organic matter composition in sediments of the Northern
      Adriatic Sea: response to a river plume.
AB  - Exoenzymatic activities (aminopeptidase and b-glucosidase) and organic matter
      composition were investigated in June 1996 and February 1997 in the sediment of
      two areas of the Adriatic Sea differently influenced by the Po river. Protein,
      carbohydrate, and lipid concentrations were comparable to those reported in most
      productive systems. Sediment chlorophyll a and biopolymeric carbon concentrations
      in June were twice as high as in February, but highest exoenzymatic activities
      and organic matter turnover rates were observed in February (with aminopeptidase
      activities 10 times higher than in June). The accumulation of organic matter and
      lower protein and carbohydrate turnover rates observed in June were the result of
      a different biochemical composition of organic matter in the two sampling
      periods. In June, organic matter was characterized by a more refractory
      composition. The consequent reduction of available organic substrate was
      associated with a decrease in the exoenzymatic substrate affinity. Lower organic
      matter turnover rates were also observed in deeper sediment layers. In February,
      the freshwater plume was almost completely confined to the northern area, whereas
      in June it was extended to the southern area. The results suggest that river
      inputs influence the biochemical composition and distribution of the sediment
      organic matter and exoenzymatic activities in coastal marine sediments.

PMID- 12219265
TI  - Spatial and temporal variation of the intestinal bacterial community in
      commercially raised broiler chickens during growth.
AB  - The objective of this study was to determine whether host, compartment, or
      environmental specific factors play an important role in the establishment of the
      intestinal microflora in broiler chickens during growth. This objective was
      addressed using a 16S rDNA approach. PCR-amplicons from the V6 to V8 regions of
      the 16S rDNA of intestinal samples were separated by denaturing gradient gel
      electrophoresis (DGGE). The number of bands in all intestinal compartments
      increased when broilers grew older, indicating that the dominant bacterial
      community becomes more complex when chickens age. Each chicken had a unique
      banding pattern for all locations in the intestinal tract, irrespective of the
      age of chickens. This suggests that host-related factors affect the establishment
      of the dominant bacterial community. Banding patterns of intestinal compartments
      within one chicken were different from each other for broilers older than 4 days,
      except for both ceca which were highly similar. In 4-day-old broilers, banding
      patterns from crop, duodenum, and ileum were very similar. We conclude that
      (unknown) host specific factors play an important role in the development of the
      intestinal bacterial community in each broiler chicken. Furthermore, compartment
      specific factors play an important role in the bacterial development of each
      intestinal compartment within one chicken.

PMID- 12219267
TI  - [CO(2) and Er:YAG lasers in dermatology and aesthetic surgery].
AB  - In the past few years, the spectrum of indications for ablative lasers in
      dermatology and aesthetic medicine has been expanded due to technological
      innovations. In the following, technical basics, laser-tissue interactions,
      indications for the CO(2) and Er:YAG laser and laser treatment management are
      described. In addition, side effects and reactions associated with the use of
      these laser systems are listed and compared.

PMID- 12219266
TI  - Presence of anaerobic bacteroides in aerobically grown microbial granules.
AB  - Microbial granules were grown in a column-type sequential aerobic sludge blanket
      reactor inoculated with activated sludge flocs taken from a wastewater treatment
      plant and containing a medium with glucose as the main carbon source. The reactor
      selected for granules that could settle rapidly by employing a short settling
      time of 2 min. Matured granules with diameters between 2 and 3 micro m were
      examined for anaerobic bacteria as their presence can signal the onset of
      diffusion limitation problems that can potentially diminish granule stability due
      to the bacterial production of fermentation gases and organic acids under
      anaerobic conditions. To detect the anaerobes in the granules, clones were
      constructed from 16S rRNA PCR amplicons. Two sequence types associated with a
      strict anaerobe Bacteroides spp. were identified from these clones. Fluorescence
      in situ hybridization (FISH) followed by confocal laser scanning microscopy
      (CLSM) demonstrated that cells of Bacteroides spp. were concentrated at a depth
      of approximately 800 micro m below the surface of the granule. Cell enumeration
      using flow cytometry showed that the percentage of labeled cells of Bacteroides
      spp. compared to total bacterial cells in the granules was 0.56%. This is the
      first study to use a suite of culture-independent techniques to report the
      presence of a defined species of anaerobic bacteria in aerobically grown
      microbial granules.

PMID- 12219268
TI  - [Oral antibiotics with antiinflammatory/ immunomodulatory effects in the
      treatment of various dermatoses].
AB  - A range of antibiotics has been shown to modify host functions apart from the
      antimicrobial potency. They may directly influence phagocyte and lymphocyte
      function, as well as chemotaxis. Effects on the generation and release of various
      cytokines involved in the inflammatory process have been studied both in vivo and
      in vitro. However, the molecular mechanisms have not been elucidated in detail.
      It is suggested that antibiotics can exert immunopharmacological effects on the
      basis of structure-activity relationships independent of their antibacterial
      activity. We present a collection of clinical studies and case reports dealing
      with the potential benefits of systemic antibiotics in the treatment of selected
      dermatoses which have primarily been classified as non-infectious. Generally
      accepted treatments such as dapsone in dermatitis herpetiformis and
      leukocytoclastic vasculitis or chloroquine in lupus erythematosus have not been
      considered. Based on existing clinical trials with a higher number of cases the
      following antibiotics have been shown to be effective: erythromycin in bullous
      pemphigoid and pityriasis rosea as well as tetracyclines in pemphigus vulgaris,
      bullous pemphigoid and pustulosis palmaris et plantaris. However, most reports
      have to be viewed critically due to the uncontrolled study design, particularly
      in dermatoses with a tendency to spontaneous resolution. Despite this lack of
      evidence-based data, it is important for the clinician to know about the
      potential use of antibiotics for various skin disorders as a primary treatment
      option or steroid-sparing therapeutic adjunct. In clinical practice the use of
      antibiotics depends on various factors including the severity of the disease, the
      patient's age, contraindications to conventional therapeutic regiments and
      economic considerations.

PMID- 12219269
TI  - [Main symptom: unfulfilled wish to have children].

PMID- 12219270
TI  - [Prevalence of psychosomatic disorders in dermatologic patients. Experiences in 2
      dermatology clinics with a liaison therapy model].
AB  - INTRODUCTION: The prevalences and differences of biopsychosocial disorders were
      investigated in the dermatologic clinics of Erfurt and Giessen, where a liaison
      therapy model has been established. Different dermatological diseases were
      compared by a variety of psychological tests, and patients with the same
      diagnosis were compared between the two clinics. PATIENTS AND METHODS: We
      examined 406 patients for psychosomatic problems with diagnostic interviews and
      psychometric tests. The coping of skin disease questionnaire (CSD) and the
      Symptom Checklist (SCL-90R) served as diagnostic measures. Between 1995-2000, 71
      patients were seen in Erfurt and 335 in Giessen. The distribution of skin
      diseases and the psychosomatic disorders are shown by ICD-10 diagnoses. RESULTS:
      The comparison of an East and a West German city showed no significant
      differences in the whole group or the parallel groups using the CSD and SCL-90R.
      There was only a tendency to a greater reduction of quality of life in Erfurt.
      Patients with glossodynia evaluated themselves in all psychometric tests as very
      "normal". By contrast, patients suffering from alopecia and acne felt very
      helpless and seemed to have a need of greater psychosocial care. CONCLUSIONS: The
      biopsychosocial characteristics of the patients treated in the dermato
      psychosomatic units in Erfurt and Giessen show no significant differences.
      Patients with diseases such as alopecia and acne are underestimated in regard to
      the need for additional psychosocial care. The liaison therapy model is an
      effective approach to diagnose psychosomatic-dermatological disorders and decide
      if further psychosomatic treatment is indicated.

PMID- 12219271
TI  - [Initial scleromyxedema. Successful treatment with melphalan].
AB  - Scleromyxedema is a rare mucinous disease without thyroid dysfunction, associated
      with a monoclonal gammopathy. The deposits of mucin in the skin and other organs
      such as the cardiovasculary system, determine the prognosis of the disease. A 74
      year old patient with initial scleromyxedema is described, in whom a pulse
      therapy with melphalan was initiated already in the early stages of the disease.
      Four cycles of melphalan in combination with prednisolon led to a complete and
      sofar stable remission of the disease.

PMID- 12219272
TI  - [Purpura fulminans. A fatal consequence of a widely used medication?].
AB  - A 39-year old man developed purpura fulminans, a manifestation of disseminated
      intravascular coagulopathy, with rhabdomyolsis following the i.m. injection of
      diclofenac.

PMID- 12219274
TI  - [The phenomen of sudden graying of the hair in the poem "Die Fusse im Feuer" by
      Conrad Ferdinand Meyer].
AB  - In his poem "Die Fusse im Feuer" Conrad Ferdinand Meyer (1825-1898) describes in
      detail the phenomenon of sudden graying of the hair. The protagonist is a
      Huguenot nobleman who hosts the man who has tortured to death his wife some years
      ago without killing him despite ample opportunities. Sudden whitening of the hair
      has been used as literary stylistic means with the aim to demonstrate extreme
      psychological stress to the world, without confirmation of its occurrence in each
      case.

PMID- 12219275
TI  - Angiogenesis and Cancer.
AB  - Tumor development, growth and progression depends on an adequate vascular supply,
      which derives from the host vasculature. This process involves complex
      interactions between tumor cells and nonneoplastic vasculature, the immune
      system, and the connective tissues. Tumor angiogenesis refers to the development
      of new vessels within the tumor. An imbalance between angiogenic growth factors
      and inhibitors released by the tumor cells and/or endothelial and inflammatory
      cells is necessary to produce tumor neovascularization. In the last two decades,
      several studies have clarified the main aspects of this phenomenon, although
      further analysis will be necessary to understand if tumoral neoangiogenesis can
      play a pivotal role as a potential target for innovative anticancer therapies.
      Here, I review and update the basic aspects of tumor angiogenesis, as well as the
      role of the quantitative analysis of tumor vasculature as an independent
      prognostic indicator in human cancers.

PMID- 12219273
TI  - [Allergic vasculitis following ingestion of celecoxib?].
AB  - A 76-year-old patient developed cutaneous vasculitis on the lower legs on the 8th
      day of treatment with the selective cox-2-inhibitor celecoxib (Celebrex((R))) and
      the proton-pump inhibitor omeprazole. The patient had no history of allergic
      reactions. The patient had already been treated previously with omeprazole
      without any side effects. A cutaneous biopsy confirmed the diagnosis of
      leucocytoclastic vasculitis. The purpuric skin lesions regressed within 3 weeks
      after withdrawing the two newly introduced drugs. We discuss the potential role
      of Celecoxib in triggering this vasculitis.

PMID- 12219276
TI  - Laser Tissue Welding - Poised for the New Millenium.
AB  - Laser tissue welding is a relatively new technique, which was initially described
      only about 30 years ago. Over the past 10 years, the implementation of protein
      solders has redefined the field. Alternative methods of wound closure and of
      tissue approximation have been quickly accepted in clinical medicine. The
      techniques and theory involved in performing laser tissue welding may soon be
      essential knowledge for all surgeons. Just as laparoscopy has become a mainstay
      for general surgeons and urologists, novel mechanisms of tissue approximation
      will continue to replace older, less efficacious techniques.

PMID- 12219277
TI  - Hand-Assisted laparoscopic Surgery.
AB  - Hand-assisted laparoscopic surgery (HALS) has been sporadically described in the
      past to assist the surgeon during operations of complexity or when operations
      require specimen removal. The hand will offer the surgeon an advantage in terms
      of tactile feedback, exposure, retraction, or orientation so that it will enable
      him or her to operate with greater safety and efficiency. The fundamental pre
      requisite for successful HALS is a reliable hand-assist device. We perform HALS
      for complex advanced laparoscopic surgery where it may save time, increase
      accuracy and improve safety. Additionally, this approach is considered for any
      operation that requires specimen removal, since an enlarged incision may be
      required. Early introduction of the hand may facilitate dissection and specimen
      removal.

PMID- 12219278
TI  - The Impact of Technology on the Resolution of Minimally Invasive Training and
      Credentialing Challenges of the 21st Century.
AB  - After the meteoric entry of minimally invasive surgery onto the general surgery
      scene 9 years ago, it currently stands at a crossroads with regard to the 21st
      century. Many challenges hamper safe and costeffective deployment of minimally
      invasive techniques. There must be a stabilization and reduction of complication
      rates associated with laparoscopic cholecystectomy. Common bile duct injuries are
      in fact two to three times higher for laparoscopic cholecystectomy than for the
      open procedure. This matter has been discussed only at local morbidity and
      mortality conferences or at national meetings. Patients are being injured. The
      surgical community has failed to police itself and the public knows it. This led
      in 1992 to New York State health officials setting standards of training and
      surgeon preparedness for performing laparoscopic cholecystectomy. If surgeons
      don't handle the problem, the politicians and the lawyers soon will.

PMID- 12219279
TI  - Preventing Staphylococcus Infections in High-Risk Patients.
AB  - UP to 30% of those who undergo surgery potentially develop a surgical site
      infection depending on the procedure performed. Infection increases the risk of
      further complications, lengthens hospital stays and increases management costs. A
      significant proportion of surgical site infections are caused by Staphyloccoccus
      spp. and prior nasal carriage is a risk factor for post surgical infection.

PMID- 12219280
TI  - A New Operating Room Concept For Minimal Invasive Surgery.
AB  - Since 1990 new developments have found their way into almost every area of
      minimally invasive surgery (MIS), and nowadays, 90% of all gynecological
      operations and 80% of all abdominal operations can be performed by this approach.
      In contrast to surgical development, operating room (OR) design has not
      progressed much over the past half century. While a number of surgical suites
      have been designed for specific specialties, more commonplace is the flexible OR
      concept.

PMID- 12219281
TI  - New Articulating Instruments for Laparoscopic Surgery.
AB  - Over the last decade, the laparoscopic approach has become the preferred method
      of intervention for many procedures, including cholecystectomy, appendectomy,
      inguinal hernia repair, lung biopsy, hysterectomy, and numerous orthopaedic
      procedures. Laparoscopic surgery is not an intuitive skill and must be developed
      through long hours of training, practice, and clinical experience. While surgeons
      may become proficient in the use of current laparoscopic instruments, many of
      them feel the advancement of laparoscopic surgery is hampered by the limited
      functionality of their instruments.

PMID- 12219282
TI  - Treatment of Venous Ulcers Using a Bilayered Living Skin Construct.
AB  - Venous ulcers are a common cause of pain and suffering in the elderly US
      population. Up to 1 million individuals suffer from this disease, and the true
      costs in terms of medical care and quality of life are only beginning to be
      appreciated. Bioengineered skin constructs are being used increasingly to treat
      venous ulcers with some success and can be used if traditional first-line
      treatment methods fail.

PMID- 12219283
TI  - Three-Dimensional Quantitative Analysis of Scintigraphic Tomographic Images after
      Elastic Transformation to a Template.
AB  - The diagnostic information in scintigraphic images is generally not contained in
      specific morphological image attributes, but in the regional distribution of
      count rate densities across the organ volumes. In a subclass of scintigraphic
      images, the evaluation is actually based on a dual comparison.

PMID- 12219284
TI  - Hand-Assisted Laparoscopic Splenectomy.
AB  - The success of laparoscopic cholecystectomy has resulted in the broad application
      of minimally invasive techniques in many surgery specialties. The theoretical
      advantages of laparoscopy over conventional open operations, including less
      postoperative pain, faster overall recovery, and better cosmetic results have
      been achieved leading to its acceptance by surgeons and the public alike.
      Numerous abdominal procedures have been adapted to minimally invasive approaches
      including bowel resection, inguinal and ventral hernia repair, anti-reflux
      techniques, and solid organ removal such as splenectomy.

PMID- 12219285
TI  - Dysphagia after Laparoscopic 360 Repair for Gastroesophageal Reflux Disease.
AB  - In comparison to medical treatment, antireflux surgery is recognized as an
      effective, efficient and longlasting therapy, as well as the only treatment that
      is able to modify the natural history of gastroesophageal reflux disease (GERD).
      The 360 fundoplication is the most widely used surgical procedure for GERD.
      Although performed in the era of H2-blockers and open surgery, comparison of the
      so-called Nissen repair to both symptomatic and continuous medical therapies
      concluded that surgery was superior to medical therapy in every outcome measure
      used.

PMID- 12219286
TI  - Potential Applications of Microendoscopy in Surgery.

PMID- 12219287
TI  - New Device for Hand-Assisted Laparoscopic Surgery.
AB  - Laparoscopic surgery has undergone a rapid evolution since the first laparoscopic
      cholecystectomy of Erich Muhe in 1985. Many surgeons felt that further
      technological success would be related not only to increasing experience and
      skill of surgeons, but also technological advances which would enable surgeons to
      perform increasingly more difficult and complex tasks. Progress has been rapid
      for some, but broad acceptance by surgeons has been slow.

PMID- 12219288
TI  - Treatment of Morbid Obesity Using an Adjustable Gastric Banding System.
AB  - Morbid obesity is a serious disease that is responsible for several co-morbid
      conditions. Patients with a body mass index of over 40 kg/m2 will require
      surgical intervention if a dietary program fails. In the US, patients who are
      morbidly obese number approximately 8 million. At present, three conventional
      operations, with acceptable early and late complication rates, are performed most
      frequently worldwide: vertical gastroplasty (VRG), vertical banded gastroplasty
      (VBG), and gastric bypass (GB). In this article, we describe our experience with
      the LAP-BAND technique, and in particular with the new LAP-BAND adjustable
      gastric banding system (LAGB), which further reduces postoperative complications
      and reoperations.

PMID- 12219289
TI  - Endoscopic Adrenalectomy Using Ultrasonic Cutting and Coagulating.
AB  - Endoscopic adrenalectomy, since its initial description in 1992 by Gagner et al.
      in Canada and by Higashaihara in Japan has emerged as the standard of care in the
      treatment of patients with benign adrenal neoplasms. It has been shown to be as
      effective as open surgery in treating adrenal pathology, with improvements in
      pain, cosmesis and duration of hospitalization.

PMID- 12219290
TI  - Comparative Study of the Use of a Suturing System and Titanium Clips.
AB  - There is a need for secure and easy methods for suturing in laparoscopic surgery,
      no matter whether vessels are to be ligated, two structures sutured together, or
      the cystic duct is to be occluded in cholecystectomy. Laparoscopic suturing can
      be done with a suture, using automatic sewing devices or clips. Improper ligation
      of a vessel for example can result in bleeding, which is more difficult to treat
      in a laparoscopic procedure than in an open procedure. By using a Roeder knot in
      laparoscopic suturing, tying of the knot requires some expertise and makes the
      procedure more complicated and time-consuming.

PMID- 12219291
TI  - Endo-Drgan Surgery: a New Approach to Intragastric Lesions.
AB  - Gastric endo-organ surgery is a minimally invasive procedure combining the use of
      gastroesophageal endoscopy and laparoscopy to approach intragastric problems that
      require surgical intervention. The advantages include: less scarring; shorter
      hospital stays; and less postoperative discomfort than conventional laparotomy.
      The technique requires placement of two or three percutaneous endoscopic
      gastrostomies in various positions on the gastric wall. Filipi et al. developed a
      percutaneous endoscopic gastrostomy (PEG) that is large enough to allow the use
      of 5 and 10mm laparoscopic instruments for intragastric surgery. In this article
      we review the complications related to the introduction of this access port.

PMID- 12219292
TI  - The High-Risk Surgical Patient: Current Management Strategies to Reduce Morbidity
      and Mortality from Organ Dysfunction in Surgical Intensive Care.
AB  - A number of patients undergoing major surgery have an associated high morbidity
      leading to a long stay in the intensive care unit. This group of patients can be
      regarded as high risk, as their mortality rate is in the region of 20 to 30%. The
      high-risk patient is likely to have at least one of the characteristics listed in
      Table 1. Perioperative cardiac morbidity remains the leading cause of
      postoperative mortality. Although we can now support patients through the early
      phase of shock, trauma or other life-threatening illness, some will go on to
      develop progressive failure of one or more vital organs. In this article, we
      review some of the current processes of care that may improve outcomes in these
      surgical patients, as improving patient outcome is the purpose of medical care.

PMID- 12219293
TI  - Vein Harvest: Minimally Invasive Techniques and Reduction in Complications.
AB  - Revascularization of the coronary or lower extremity circulation ideally requires
      an autologous conduit. The saphenous vein is the most commonly used graft.
      Minimally invasive surgical techniques for harvesting of the greater saphenous
      vein (GSV) are gaining popularity. With better instruments, critical evaluation
      of techniques and longer follow-up of patients, the outcome of such vein
      harvesting is improving. An increasing number of authors are reporting a variety
      of techniques with reduction in wound complications compared to conventional
      surgery.

PMID- 12219294
TI  - Management of Infection in the Surgical Patient.
AB  - While surgical infections are seemingly a heterogeneous group of disease
      entities, there are several common features that permit a general approach to
      their diagnosis and management. These properties include: the polymicrobial
      nature of the flora in most infections, the association of the infection with
      some underlying pathological process, and appropriate treatment often includes
      both broad-spectrum antimicrobial therapy and some surgical or radiological
      intervention to promote eradication of the infection. For the purpose of this
      review, intra-abdominal infection will be used as the prototypical surgical
      infection because it embodies many of the general features of most infections.

PMID- 12219295
TI  - An Update on Laparoscopic Hysterectomy and Pelvic Floor Reconstruction.
AB  - Laparoscopic hysterectomy and pelvic floor reconstruction have recently undergone
      some degree of evolution. New instrumentation has appeared, such as the vaginal
      delineator, but overall most of the instruments used have remained basically
      unchanged. This is related mostly to the need of keeping costs down by limiting
      the use of disposable instrumentation. For pelvic reconstruction, the
      laparoscopic approach is now usually considered the optimal approach, as it
      allows the surgeon to visualize structures that the vaginal surgeon could in the
      past only palpate.

PMID- 12219296
TI  - Subfascial Endoscopic Perforator Vein Surgery [SEPS] and Fasciotomy: Treatment of
      Severe Chronic Venous Disease.
AB  - Chronic leg ulceration affects about 1 to 2 % of the European population.
      Although the pathogenesis of venous ulceration is not completely understood, it
      is generally agreed that the transmission of high ambulatory pressures through
      incompetent perforating veins plays a major role. There are only limited data
      available to assess the long-term prognosis for leg ulcer patients.

PMID- 12219297
TI  - Endoscopic Surgery for Arterial Occlusive Disease.
AB  - Endoscopic surgery is not a recent development. In fact, the application of the
      Edison light bulb to the cystoscope in 1883 was followed by widespread use of
      endoscopy. In 1910, Jacobeaus proposed the diagnostic use of the cystoscope for
      investigation of serous cavities, and in 1922, he reported lysis of pleural
      adhesions to promote artificial pneumothorax in 40 patients with pulmonary
      tuberculosis. For the next 30 years, the thoracoscope was widely used for
      pneumolysis in tuberculosis patients, but its use waned considerably after the
      development of effective antibiotic treatment for tuberculosis. With the advent
      of laparoscopy, endoscopy has become popular again and here we review the
      application of endoscopic techniques in cardiovascular surgery.

PMID- 12219298
TI  - Minimal Access Coronary Artery Bypass Surgery.
AB  - Complete myocardial revascularization is associated with improved quality of
      life, increased overall survival, and the lack of any major adverse clinical
      events (requiring reintervention, reoperation, and readmission for recurrent
      symptoms). However, the trauma of access often exceeds the trauma of surgical
      treatment, while achieving complete revascularization. Another trade-off for
      complete revascularizarion is often increased morbidity, mortality, cost and post
      operative stay.

PMID- 12219299
TI  - Mitral Valve Repair: the Multimodal Approach and the Role of Minimally Invasive
      Procedures.
AB  - In recent years mitral valve repair has gained increasing acceptance as the
      preferred treatment for mitral insufficiency. Mitral valve repair has many
      advantages. The surgical risk is lower than prosthetic valve replacement.
      Improved preservation of left ventricular function due to maintenance of the
      papillary muscle - mitral annular continuity - has been demonstrated.
      Thromboembolism is rare after mitral repair in patients in sinus rhythm. These
      patients receive no coumadin and thus are free from bleeding complications. The
      repaired valves have been shown to have durability comparable to or better than
      prosthetic valves.

PMID- 12219300
TI  - Mitral Valve Surgery Using a Modified Superior Left Atrial Approach.
AB  - Most surgeons use a longitudinal right lateral left atrial incision behind the
      inter-atrial groove for the exposure of the mitral valve, even though several
      other surgical techniques have been described. The shortest route to the mitral
      valve is, however, through the roof of the left atrium, where the incision is
      closest to the mitral annulus. This was first described by Meyer et al., but the
      approach became unpopular because of its technical difficulties and inadequacies.
      We have modified this technique, making it safer, easier and adaptable to any
      type of mitral surgery. We describe our experience with 53 patients who had
      mitral valve surgery using this modified approach. All of the operations were
      performed by the same surgeon over an 18 month period with consistently
      satisfactory results.

PMID- 12219301
TI  - Transit-lime Ultrasound Flowmetry in CABG.
AB  - Intraoperative measurement of flow allows functional evaluation of coronary
      bypass grafts and may be predictive of a patient's immediate and late outcome
      after myocardial revascularization as it permits early detection of technical
      errors. Many different methods have been used to assess the quality of the
      anastomosis intraoperatively. Angiography is considered the gold standard
      technique to which all other methods should be compared. However, it is invasive,
      costly, time consuming, and not always readily accessible in the operating room.

PMID- 12219302
TI  - Port Access Cardiac Surgery.
AB  - The port-access technique for cardiac surgery was recently developed at Stanford
      University in California as a less invasive method to perform some cardiac
      operations. The port-access system has been described in detail elsewhere. It is
      based on femoral arterial and venous access for cardiopulmonary bypass (CPB) and
      on the adoption of a specially designed triple-lumen catheter described
      originally by Peters, and subsequently modified and developed in the definitive
      configuration called the endoaortic clamp.

PMID- 12219303
TI  - Total Coronary Artery Revascularization Through a Mini-Sternotomy.
AB  - Revascularization of all significantly stenosed vessels remains the goal of
      coronary artery bypass surgery. Recent improvements in endoscopic instruments
      have resulted in the evolution of selective left anterior descending artery
      bypass grafting through a limited anterior small thoracotomy (LAST) incision. A
      major limitation of this technique is the inaccessibility for complete surgical
      revascularization in multivessel disease. In this article, we describe a
      minimally invasive technique for total coronary artery revascularization that
      combines conventional surgical techniques with the advantages of minimally
      invasive surgery. We have performed total coronary revascularization in 52
      patients over a period of 16 months with consistently good results.

PMID- 12219304
TI  - The Rotating Platform Mobile Bearing Total Knee Arthroplasty.
AB  - The recent evolution of total knee arthroplasty (TKA) has been substantial and
      unlike that of total hip arthroplasty (THA). The current THA technique is similar
      to that initially developed and perfected by Professor John Charnley in the mid
      1960s. The ball-and-socket articulation of the hip is simple and reproducible
      biomechanically. The long term (20 years and longer) results with total hip
      arthroplasty have been very satisfactory. The THA prosthetic designs of today
      remain similar to those of years past. Improvements have been in biomaterials,
      methods of fixation and surgical technique. The total knee arthroplasty
      prostheses of today differ greatly from their predecessors.

PMID- 12219305
TI  - Instability of the Trapezio Metacarpal Joint: Related Arthritis and Surgery.
AB  - Arthritis of the trapezio metacarpal joint (TMJ) is a very frequent condition,
      which affects women more than men, especially in the fifth or sixth decade of
      life. It can be very painful and disabling and the patient will need surgery for
      relief even if it can result in painless stiffening (in adduction of the
      metacarpal and hypertension of the metacarpal, which in turn is very disabling).
      TMJ arthritis is rarely primary or idiopathic; in general, it is secondary to
      instability of the joint, which, in turn, may be primary or secondary.

PMID- 12219306
TI  - Retrograde Nailing of Femur Shaft Fractures Through the Intercondylar Notch for
      Specific Indications: 10 Years Experience.
AB  - Closed antegrade intramedullary nailing is the current standard of care for the
      treatment of femoral shaft fractures. This technique has been shown to have
      excellent results demonstrated by a high rate of fracture union and the low
      incidence of infection. However, there are complications specific to antegrade
      intramedullary nailing, as well as specific injury patterns that make this
      treatment less attractive.

PMID- 12219307
TI  - Extensively Coated Cementless Femoral Components in Revision Hip Arthroplasty.
AB  - A septic loosening and osteolysis can compromise the available host bone in
      patients requiring revision hip arthroplasty. Secure fixation of revision femoral
      components may not be possible if reliant only on proximal femoral bone for
      biologic fixation or cement interdigitation. The challenge for the revision
      arthroplasty surgeon is to find the best method to secure the implant in a femur
      with deficient bone proximally that will provide stability for load bearing and
      motion. In addition to providing stability, the implant must be durable and
      maintain long-term fixation. With over 16 years of experience with fully porous
      coated femoral revision implants, we have found that maximizing prosthetic-bone
      fit in the proximal femoral diaphyseal bone provides reliable long-term fixation
      in the majority of femoral revision cases.

PMID- 12219309
TI  - Global Management of Total Hip and Total Knee Arthroplasty Patient Populations: a
      New, Comprehensive Approach to Deep Vein Thrombosis Prophylaxis.
AB  - Venous thromboembolic disease remains a common and potentially fatal complication
      after total joint arthroplasty. The incidence of deep vein thrombosis (DVT) has
      been reported to be between 5% and 60% in a number of studies using a variety of
      prophylaxis regimens. Symptomatic pulmonary embolism has been documented as high
      as 23%, while fatal pulmonary embolism, although relatively infrequent, remains
      one of the most catastrophic complications of total joint arthroplasty.

PMID- 12219308
TI  - A Long Straight Stem with Distal Interlocking for Uncemented Stem Revision in
      THR.
AB  - Femoral revision in total hip replacement (THR) is often demanding due to severe
      bone defects of the proximal femur. The surgical technique must provide
      sufficient stability in the distal femur. However, long-term stability depends on
      preserving or even rebuilding proximal bone stock.

PMID- 12219310
TI  - Surgical Technique in Total Hip Arthroplasty Utilizing the Anterolateral
      Approach.
AB  - The surgical approach is an important element in the quality of total hip
      replacement. Adequate surgical exposure based upon thorough fundamental knowledge
      of anatomy facilitates surgery and ensure optimum results in total hip
      replacement. Several surgical exposure techniques are utilized and have been
      described in the literature; all stress the importance of visualization of the
      acetabulum and the proximal femur in affording an atraumatic, expedient entry
      into the hip joint. Additionally, surgical exposure should be versatile, allowing
      for development to easily accommodate revision scenarios.

PMID- 12219311
TI  - Management of Contained Medial [Protrusiol] Acetabular Defects in Revision Total
      Hip Arthroplasty.
AB  - Medial migration of the acetabular cup and protrusio of the medial wall is a well
      recognized failure mechanism of acetabular fixation in cemented total hip
      arthroplasty. In the protruded acetabulum, a medialized position of the
      acetabular component is associated with increased medial cortical bone stresses,
      while more lateral positioning reduces the medial stresses. Use of a protrusio
      ring or medial wire mesh may limit medial migration. However, late failure of
      acetabular revision reconstructions can occur when cemented protrusio rings or
      wire mesh reinforcement are used without bone grafting.

PMID- 12219312
TI  - Computer Modeling in Bone Research.
AB  - Computer modeling has had an undoubtedly enormous impact on the field of bone
      research in recent years. Development of advanced computer based models has
      permitted researchers to explore a vast area of musculoskeletal science from the
      complex biophysical stimuli at the cellular level to the mechanical behavior of
      heterogeneous skeletal structures. Furthermore, computer modeling has given
      significant impetus to the impressive progress of modern bone implant
      development. With recent advances in computers, faster hardware and increasingly
      sophisticated software, the prospects for the future of computer-based bone
      research appear more exciting than ever.

PMID- 12219313
TI  - Uncommon Complications of Renal Transplantation.
AB  - As a result of advances in surgical technique and immunosuppressive therapy, the
      incidence and the consequences of post-transplant surgical complications has
      decreased. However, surgical complications still cause considerable morbidity and
      test the skills of the surgical team. Several reviews have been published
      analyzing the incidence of these complications and the management strategies
      employed to correct them. We report some uncommon or rare complications
      encountered in our unit after the introduction of low-dose steroids or steroid
      free immunosuppressive protocols.

PMID- 12219314
TI  - Principles of Evidence Based Screening for Cancers.
AB  - Cancer is a major public health concern. Current estimates suggest that
      approximately 3 out of every 10 people will be diagnosed with cancer at some
      point during their lifetime. The American Cancer Society (ACS) estimates that
      about 1.25 million people in the US will be diagnosed with cancer each year, with
      nearly 550,000 subsequent deaths. The financial burden of cancer and cost in
      human lives is staggering. In 1990,it was estimated that the economic burden from
      cancer in the US was $104 billion: $35 billion for direct costs of prevention,
      diagnosis and treatment; $12 billion for morbidity costs (economic losses caused
      by days lost from productive activity because of illness-related disability); and
      $57 billion in mortality costs (lost economic output measured by loss in earnings
      because of premature death of productive individuals).

PMID- 12219315
TI  - Progression of Gastric Mucosal Dysplasia of the Postgastrectomy Stomach.
AB  - Gastric cancer, if diagnosed at the symptomatic stage, has a poor prognosis, with
      an overall 5 year survival of about 5%. The surgical treatment of early gastric
      cancer increases this 5-year survival rate to 90%. In Japan, endoscopic
      surveillance has increased the proportion of gastric cancer detected at an early
      stage from 15% in 1960 to 50% in 1985, and the overall 5 year survival has been
      increased from 35% to 70%. Mass screening in Japan is worthwhile because the
      incidence of gastric cancer is about 80 cases per 100,000 population per annum
      (age standardized). But in other countries where the incidence is much lower the
      case for mass screening is weak and selective screening of those at high risk is
      advocated.

PMID- 12219316
TI  - Fibromyalgia and post-traumatic stress disorder: another piece in the
      biopsychosocial puzzle.

PMID- 12219317
TI  - Vasculitis secondary to staphylococcal Protein A immunoadsorption (Prosorba
      column) treatment in rheumatoid arthritis.
AB  - OBJECTIVE: Vasculitis is a rare complication of immunoadsorption treatment with
      staphylococcal Protein A (Prosorba column). The prevalence, clinical
      characteristics, pathophysiology, treatment, and outcome of vasculitis secondary
      to immunoadsorption treatment is not known. METHODS: The authors describe a 57
      year-old woman with rheumatoid arthritis (RA) resistant to methotrexate and
      etanercept, who developed severe leukocytoclastic vasculitis after the 9th weekly
      treatment with Prosorba column. She developed rapidly progressive crescentic
      glomerulonephritis and required treatment with cyclophosphamide and high-dose
      prednisone. Subsequently, renal function stabilized and RA remitted. Through the
      literature search and by reviewing information submitted to Cypress Biosciences
      Inc (manufacturer of Prosorba columns), available world literature on vasculitis
      secondary to Prosorba column treatment was compiled. RESULTS: Immune complex
      deposition of staphylococcal Protein A (SPA)/SPA antibodies in the glomeruli
      precipitated the renal disease in our patient. Twenty cases of vasculitis
      (calculated prevalence, 1 per 400), 5 with internal organ involvement, have been
      reported in patients treated with Prosorba column for thrombocytopenic purpura.
      Seven RA patients treated with Prosorba column developed vasculitis (prevalence,
      7 per 400), 3 with internal organ involvement. CONCLUSIONS: Vasculitis secondary
      to staphylococcal Protein A immunoadsorption therapy occurs rarely and appears to
      be related to development of SPA/SPA antibody immune complexes. Rheumatologists
      should be aware of this potentially serious complication of the Prosorba column
      treatment for RA.

PMID- 12219318
TI  - Potential mechanism of action of intra-articular hyaluronan therapy in
      osteoarthritis: are the effects molecular weight dependent?
AB  - BACKGROUND: Hyaluronan, or hyaluronic acid (HA), is the major hydrodynamic
      nonprotein component of joint synovial fluid (SF). Its unique viscoelastic
      properties confer remarkable shock absorbing and lubricating abilities to SF,
      while its enormous macromolecular size and hydrophilicity serve to retain fluid
      in the joint cavity during articulation. HA restricts the entry of large plasma
      proteins and cells into SF but facilitates solute exchange between the synovial
      capillaries and cartilage and other joint tissues. In addition, HA can form a
      pericellular coat around cells, interact with proinflammatory mediators, and bind
      to cell receptors, such as cluster determinant (CD)44 and receptor for
      hyaluronate-mediated motility (RHAMM), where it modulates cell proliferation,
      migration, and gene expression. All these physicochemical and biologic properties
      of HA have been shown to be molecular weight (MW) dependent. OBJECTIVE: Intra
      articular (IA) HA therapy has been used for the treatment of knee osteoarthritis
      (OA) for more than 30 years. However, the mechanisms responsible for the reported
      beneficial clinical effects of this form of treatment remain contentious.
      Furthermore, there are a variety of pharmaceutic HA preparations of different MW
      available for the treatment of OA, but the significance of their MWs with respect
      to their pharmacologic activities have not been reviewed previously. The
      objective of the present review is to redress this deficiency. METHODS: We
      reviewed in vitro and in vivo reports to identify those pharmacologic activities
      of HA that were considered relevant to the ability of this agent to relieve
      symptoms and protect joint tissues in OA. Where possible, reports were selected
      for inclusion when the pharmacologic effects of HA had been studied in relation
      to its MW. In many studies, only a single HA preparation had been investigated.
      In these instances, the experimental outcomes reported were compared with similar
      studies undertaken with HAs of different MWs. RESULTS: Although in vitro studies
      have generally indicated that high MW-HA preparations were more biologically
      active than HAs of lower MW, this finding was not confirmed using animal models
      of OA. The discrepancy may be partly explained by the enhanced penetration of the
      lower MW HA preparation through the extracellular matrix of the synovium, thereby
      maximizing its concentration and facilitating its interaction with target
      synovial cells. However, there is accumulating experimental evidence to show that
      the binding of HAs to their cellular receptors is dependent on their molecular
      size; the smaller HA molecular species often elicits an opposite cellular
      response to that produced by the higher MW preparations. Studies using large
      animal models of OA have shown that HAs with MWs within the range of 0.5 x 10(6)
      1.0 x 10(6) Da were generally more effective in reducing indices of synovial
      inflammation and restoring the rheological properties of SF (visco-induction)
      than HAs with MW > 2.3 x 10(6) Da. These experimental findings were consistent
      with light and electron microscopic studies of synovial membrane and cartilage
      biopsy specimens obtained from OA patients administered 5 weekly IA injections of
      HA of MW = 0.5 x 10(6)-0.73 x 10(6) Da in which evidence of partial restoration
      of normal joint tissue metabolism was obtained. CONCLUSIONS: By mitigating the
      activities of proinflammatory mediators and pain producing neuropeptides released
      by activated synovial cells, HA may improve the symptoms of OA. In addition, HAs
      within the MW range of 0.5 x 10(6)-1.0 x 10(6) Da partially restore SF
      rheological properties and synovial fibroblast metabolism in animal models. These
      pharmacologic activities of HA could account for the reported long-term clinical
      benefits of this OA therapy. However, clinical evidence has yet to be described
      to support the animal studies that indicated that HAs with MW > 2.3 x 10(6) Da
      may be less effective in restoring SF rheology than HAs of half this size.

PMID- 12219319
TI  - Prevalence of post-traumatic stress disorder in fibromyalgia patients:
      overlapping syndromes or post-traumatic fibromyalgia syndrome?
AB  - OBJECTIVES: The primary aim of this study was to assess the frequency of post
      traumatic stress disorder (PTSD) in patients with the fibromyalgia syndrome
      (FMS). The influence of gender on measures of PTSD in fibromyalgia (FM) patients
      also was examined. METHODS: Seventy-seven consecutive patients (40 women and 37
      men) who fulfilled the criteria for FM were asked to complete questionnaires
      measuring the prevalence and severity of symptoms of PTSD, anxiety, and
      depression. The subjects were divided in 2 groups based on the presence or
      absence of PTSD symptoms. RESULTS: In this study, 57% of the FM sample had
      clinically significant levels of PTSD symptoms. The FM patients with PTSD
      reported significantly greater levels of avoidance, hyperarousal, reexperiencing,
      anxiety, and depression than did the patients without clinically significant
      levels of PTSD symptoms. The prevalence of PTSD among the FM patients in this
      study was significantly higher than in the general population. Women with FM and
      PTSD reported a greater number of past traumatic events than did their male
      counterparts. CONCLUSIONS: The results represent the first comprehensive study
      applying structured clinical assessment of trauma exposure and PTSD to a group of
      FM patients. This study shows a significant overlap between FM and PTSD,
      according to the currently accepted diagnostic criteria for each.

PMID- 12219320
TI  - Clinical manifestations and outcome of polyarthralgia associated with chronic
      lymphocytic thyroiditis.
AB  - OBJECTIVES: Arthralgia is among the most frequent musculoskeletal symptoms
      occurring in patients with chronic lymphocytic thyroiditis (CLT), often causing
      pain and physical impairment over extended periods of time. Our study aims to
      characterize arthralgia and, in particular, polyarthralgia (PA) associated with
      CLT and to evaluate the influence of thyroid replacement therapy. METHODS: Of 130
      patients affected with CLT attending the Division of Rheumatology for rheumatic
      complaints, the authors sequentially selected 20 patients with PA without any
      known rheumatic diseases. Of these 20 patients, 8 were euthyroid, 2 hyperthyroid,
      and 10 hypothyroid. The last group had never undergone therapy for thyroid
      disease; then, they were treated with thyroxine and followed up for 24 months.
      Clinical assessment included the number of joints affected by pain (NAJ), the
      visual analogic scale of pain (VAS), the duration of PA (number of days), and the
      intake of acetaminophen. RESULTS: At baseline, the only correlations in the 20
      patients with PA were between NAJ and antithyroid microsomal antibodies (r =.782;
      P <.001), thyroid stimulation hormone (r =.651; P =.001), and erythrocyte
      sedimentation rate (r =.511; P = 0.021), respectively. During follow-up, although
      symptoms improved in the 10 hypothyroid patients treated with thyroxine, a
      statistical significance was reached only after 12 months. CONCLUSIONS: Patients
      with CLT may be affected with PA severely, even in absence of hypothyroidism.
      Replacement therapy with thyroxine in hypothyroid patients with CLT induced a
      progressive but gradual improvement of symptoms.

PMID- 12219321
TI  - Th1/Th2 cytokine imbalance in patients with Sjogren syndrome secondary to
      hepatitis C virus infection.
AB  - OBJECTIVE: To investigate if the serum immunologic profile, as delineated by
      serum circulating levels of Th1/Th2 cytokines and autoantibodies, is different in
      patients with Sjogren syndrome (SS) with and without hepatitis C virus (HCV)
      infection. METHODS: This study included 20 patients with HCV-related SS and 47
      consecutive patients with primary SS. All fulfilled 4 or more of the modified
      1996 European criteria for SS. Serum levels of interleukin (IL)-2 (pg/mL), srIL-2
      (pM), tumor necrosis factor (TNF)-alpha (pg/mL), IL-6 (pg/mL), and IL-10 (pg/mL)
      were determined using enzyme immunoassay. We also analyzed the following
      immunologic tests: anti-nuclear antibodies (ANA), anti-mitochondrial antibodies
      (AMA), anti-parietal cell antibodies (PCA), anti-smooth muscle antibodies (SMA),
      anti-liver-kidney microsome antibodies type-1 (LKM-1), anti-Ro/SS-A, anti-La/SS
      B, rheumatoid factor (RF), complement factors (C3 and C4), and cryoglobulins.
      RESULTS: Of the 20 patients with HCV-related SS, 18 were women and 2 men (mean
      age, 66 years). Patients with HCV-related SS had a different cytokine profile
      compared with patients with primary SS, with higher circulating levels of IL-6
      (73.6 v 33.0 pg/mL, P =.045), IL-10 (6.7 v 3.1 pg/mL, P =.01), srIL-2 (124.6 v
      72.7 pM, P =.001), and TNF-alpha (59.8 v 31.7 pg/mL, P =.003). The main
      immunologic features were ANA, detected in 75% of patients, RF in 63%,
      cryoglobulinemia in 50%, hypocomplementemia in 40%, SMA in 30%, PCA in 25%, anti
      Ro/SS-A in 25%, AMA in 20% and anti-La/SS-B in 16%. When compared with primary SS
      patients, those with HCV-related SS had a higher prevalence of AMA (20% v 2%, P
      =.025), hypocomplementemia (40% v 11%, P =.015), and cryoglobulinemia (50% v 12%,
      P =.003). CONCLUSION: Although chronic HCV infection may mimic the main clinical,
      histologic and immunologic features of primary SS, patients with HCV-related SS
      showed some differentiated characteristics, including a predominant Th2 pattern
      and a higher frequency of cryoglobulinemia and hypocomplementemia (features
      closely related to HCV). This suggests that the SS observed in some HCV patients
      should be interpreted as one of the extrahepatic manifestations of chronic HCV
      infection.

PMID- 12219324
TI  - Breast-feeding in preterm twins: Development of feeding behavior and milk intake
      during hospital stay and related caregiving practices.
AB  - In a prospective study of 13 preterm twins still in the hospital, 85% were breast
      fed, of which 46% were breast-fed exclusively. Most mothers preferred
      simultaneous breast-feeding, using the football hold. Observations and maternal
      descriptions showed differences between the twins in their development of breast
      feeding behavior, especially in sucking. The mothers' suggestions regarding
      special support for the breast-feeding mothers of preterm twins involved
      synchronizing feeding with the twins' behavioral states; twin cobedding;
      appropriate armchairs and breast-feeding pillows; experimenting with breast
      feeding positions; information about breast milk production; nurses' spontaneous
      practical assistance, encouragement, and emotional support; the provision of
      privacy; the availability of parent rooms; and opportunities for fathers'
      presence in the hospital.

PMID- 12219322
TI  - Clinical characteristics and etiologic factors of premenopausal osteoporosis in a
      group of Spanish women.
AB  - OBJECTIVES: To analyze the clinical characteristics and the principal causes of
      osteoporosis in premenopausal women. METHODS: This study included 52 osteoporotic
      premenopausal women ages 20-51 years (mean 36.2 +/- 7) who were referred to an
      outpatient rheumatology department for osteoporosis evaluation. Bone mass
      assessment, automated biochemical profile, urinary calcium excretion, and bone
      marker assays were performed on all patients. Hormonal measurements were made
      when a specific etiology was not readily apparent. The diagnosis of osteoporosis
      was defined by the presence of atraumatic vertebral fractures and/or by
      densitometric criteria. Previous skeletal fractures, weight, height, body mass
      index (BMI), age at menarche, and family history of osteoporosis also were
      recorded. RESULTS: Twenty-nine patients (56%) had idiopathic osteoporosis and 23
      (44%) had secondary osteoporosis. Fifteen patients (29%) had vertebral fractures
      and 12 had previous peripheral fractures. Patients with secondary osteoporosis
      showed higher BMI (23.2 +/- 3 v 21.2 +/- 2, P =.02) and lower femoral Z-scores of
      bone mineral density (BMD) (-2.1 +/- 0.6 v -1.5 +/- 0.9, P =.02) than those with
      idiopathic disease. The most frequent causes of secondary osteoporosis included
      Cushing syndrome, pregnancy osteoporosis, and osteogenesis imperfecta. Nearly
      half of the patients (48%) with idiopathic osteoporosis had a family history of
      osteoporosis. In addition, 11 patients (38%) with idiopathic osteoporosis had
      associated hypercalciuria. Except for an increase in urinary calcium excretion
      (248 +/- 53 v 143 +/- 47 mg/24 h, P <.0001), no other significant differences in
      the remaining variables analyzed were found between hypercalciuric and
      normocalciuric patients with idiopathic osteoporosis. CONCLUSIONS: Idiopathic
      osteoporosis was the most frequent diagnosis of pre-menopausal osteoporosis in
      our unit. These patients showed lower BMI and higher femoral neck Z-scores than
      patients with secondary causes. A family history of osteoporosis and
      hypercalciuria were factors frequently associated with this disorder.

PMID- 12219325
TI  - Gender differences in adapting to a child's chronic illness: a causal model.
AB  - This study investigated (1) the differential impact of the child's chronic
      illness (CI) on 80 fathers and 80 mothers and the psychosocial variables
      contributing to their adaptation and (2) the suitability of the causal model
      based on the Double ABCX Model to predict parents' adaptation to the child's
      illness. Eight questionnaires relating to the variables were used. Path analysis
      revealed similarities and differences between fathers and mothers. Social support
      and coping behaviors were the main variables influencing both parents'
      adaptation. Differences between fathers and mothers are discussed in this
      article. The Double ABCX Model is fairly effective in conceptualizing the process
      of parents' adaptation to the child's CI.

PMID- 12219326
TI  - Parental views on participation in their child's pain relief measures and
      recommendations to health care providers.
AB  - The purpose of this study was to describe parental views on the factors
      influencing participation in their 8- to 12-year-old hospitalized child's
      surgical pain relief measures, and the recommendations to health care providers
      concerning alleviation of their child's pain. The data were collected by a
      questionnaire completed by parents (N = 192) whose child was hospitalized in one
      of the pediatric surgical wards in the five university hospitals of Finland.
      Results revealed that most of the parents (98%) agreed to having adequate
      opportunities to participate in their child's care according to their personal
      preferences; however, only 23% of the parents totally agreed that they had a
      clearly defined role in their child's pain relief measures. Feelings such as
      concern, fear, helplessness, anxiety, and depression were commonly experienced by
      the parents during their child's hospitalization. Most of the parents'
      recommendations concerned the topic of providing information. The findings of
      this study have implications for nursing practice.

PMID- 12219327
TI  - Self-esteem in Turkish diabetic children.
AB  - Self-esteem is the state of appreciation arising from the ratification of the ego
      concept that has resulted in self-assessment of their own skills, preferences,
      and psychologic traits. If people evaluate themselves in positive terms, we say
      they have high self-esteem. Self-esteem can be evaluated in relation to factors
      such as family, parents, level of education, age, occupation, and economic
      status. Children with diabetes mellitus type 1 live with physical, personal, and
      social developments that occur rapidly and intensively during adolescence. They
      also must cope with a chronic disease that may have a negative effect on their
      lives. This study was designed to evaluate the self-esteem of the children who
      have a diagnosis of diabetes mellitus type 1 and uses a prospective design. The
      sample consisted of Turkish children between the ages 10 and 14 years old. The
      study group was selected from the patients admitted to the diabetes outpatient
      clinics of the hospitals of the university and the Social Insurance Association,
      and had a diagnosis of diabetes mellitus type 1. The control group was selected
      from healthy children who were students in a primary school.

PMID- 12219328
TI  - A model for transition from pediatric to adult care in cystic fibrosis.
AB  - With improved medical technology, many chronic medical conditions of childhood
      are now recognized as conditions of childhood onset. Appropriate treatment of
      these conditions in the adult patient is required. The pediatric setting is not
      appropriate in terms of philosophy, service delivery, and relationship with the
      patient. To design a suitable transition protocol, a survey of teenage patients
      with cystic fibrosis was carried out and the process was discussed with the
      relevant clinicians. The results of the survey indicated that young people
      identified transition to an adult service as necessary and accepted, provided
      that good preparation is given from the pediatric setting. This article provides
      a detailed example of a model of transition for cystic fibrosis services to
      encourage practice and evaluation of provision.

PMID- 12219329
TI  - Child-rearing practices of primary caregivers of HIV-infected children: An
      integrative review of the literature.
AB  - The number of human immunodeficiency virus (HIV)-infected children has increased
      because of the HIV and acquired immunodeficiency syndrome epidemic. Yet little is
      known about the child-rearing practices of these children's primary caregivers.
      The purpose of this article is to describe what is known about the child-rearing
      practices of primary caregivers of HIV-infected children. The review covers a 10
      year period from 1990 to 2000. Three electronic bibliographic databases (MEDLINE,
      CINAHL, and AIDSLINE) were explored. Key words used were HIV-positive children,
      caregivers, and child-rearing. A total of 50 papers were examined. Using the
      Matrix Method, each paper was evaluated according to five frames of reference:
      journal, purpose, sample, method, and findings. Content analysis was used to
      identity salient themes. Themes that emerged were: caregiver, child, and
      interactions or child-rearing practices. These findings affirm the parent-child
      interaction model generated by Kathryn E. Barnard and support this framework as a
      tool for investigating the relationships between these children and their
      caregivers.

PMID- 12219330
TI  - Stress factors and coping strategies of parents with children treated by
      hemodialysis: A qualitative study.
AB  - The purpose of this study was to describe the common stress factors and coping
      strategies of parents whose children had been treated by hemodialysis. This study
      was conducted by using focus group interviews. The sample was composed of 31
      parents. Five focus groups were made up from these parents. Data were analyzed by
      using the manifest content analysis method. According to the results, common
      stress factors of parents included financial and bureaucratic problems, growth
      and development of ill children, fluid-diet restriction and educational problems
      of children, lack of social support, and anxiety about losing their children at
      any moment. Coping strategies of parents were to give their attention to the
      positive side of matters, to share their feelings with their spouse or other
      parents, to cry, or pray.

PMID- 12219331
TI  - Preparing for disasters: Enhancing the role of pediatric nurses in wartime.
AB  - During the tragic terrorist attacks that occurred against the United States on
      September 11, 2001, nurses were on the front lines making a difference for
      patients, families, and children. As noted in the American Nurse, the official
      publication of the American Nurses Association, "September 11, 2001, is no longer
      just a day gone by. It now takes the place alongside other infamous dates like
      December 7, 1941, the attack on Pearl Harbor by Japan" (Trossman, 2001, p. 1).
      This article will focus on resources available for pediatric nurses to use when
      working with children and families who are either preparing for or responding to
      disasters.

PMID- 12219332
TI  - Children and the media.

PMID- 12219333
TI  - Evidence-based practice in action.
AB  - As Associate Editor for Journal of Pediatric Nursing (JPN), I will be assisting
      with evidence-based practice (EBP) submissions or other clinically based
      articles. I welcome questions, works-in-progress for constructive criticism, and
      finished submissions for review. This article comprises an overview of the EBP
      process, an EBP submission format for JPN, and 4 examples of EBP in a variety of
      pediatric clinical settings.

PMID- 12219335
TI  - High altitudes, anxiety, and panic attacks: is there a relationship?
AB  - People exposed to high altitudes often experience somatic symptoms triggered by
      hypoxia, such as breathlessness, palpitations, dizziness, headache, and insomnia.
      Most of the symptoms are identical to those reported in panic attacks or severe
      anxiety. Potential causal links between adaptation to altitude and anxiety are
      apparent in all three leading models of panic, namely, hyperventilation (hypoxia
      leads to hypocapnia), suffocation false alarms (hypoxia counteracted to some
      extent by hypocapnia), and cognitive misinterpretations (symptoms from hypoxia
      and hypocapnia interpreted as dangerous). Furthermore, exposure to high altitudes
      produces respiratory disturbances during sleep in normals similar to those in
      panic disorder at low altitudes. In spite of these connections and their clinical
      importance, evidence for precipitation of panic attacks or more gradual increases
      in anxiety during altitude exposure is meager. We suggest some improvements that
      could be made in the design of future studies, possible tests of some of the
      theoretical causal links, and possible treatment applications, such as systematic
      exposure of panic patients to high altitude.

PMID- 12219336
TI  - Obsessive-compulsive disorder with and without tics in a clinical sample of
      children and adolescents.
AB  - The purpose of this study was to discriminate subtypes of obsessive-compulsive
      disorder (OCD) in a clinical sample of children and adolescents. Sixty OCD
      patients were assessed in two outpatient psychiatric clinics; 15 patients had a
      lifetime history of tics and 45 patients had no tic history. Interviews were
      conducted with the patients and their parents by a child psychiatrist using the
      Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). The symptom checklist
      of the CY-BOCS was used to categorize obsessions and compulsions. Discriminant
      function analysis was used to compare the two groups in their symptomatology.
      There was no difference between the two groups in seven obsession categories.
      However, there was a significant difference between the two groups in seven
      compulsion categories. Ordering, hoarding, and washing compulsions were more
      common in those with no tic history. The results indicate that tic-related OCD
      may be differentiated from non-tic-related OCD early in life by the presence or
      absence of certain compulsive symptoms.

PMID- 12219337
TI  - Replication and expansion of findings related to racial differences in veterans
      with combat-related PTSD.
AB  - Racial differences in those seeking treatment at a Veterans Affairs Medical
      Center (VAMC) outpatient posttraumatic stress disorder (PTSD) treatment program
      were examined. One hundred eleven (71 Caucasian and 40 African American) veterans
      were compared on both self-report measures and interview measures of PTSD,
      depression, dissociation, and general psychopathology. Participants completed the
      following self-report measures: the Beck Depression Inventory, the Dissociative
      Experiences Scale, the Mississippi Combat PTSD Scale, and the Minnesota
      Multiphasic Personality Inventory-2 (MMPI-2). Participants also completed the
      Clinician Administered PTSD Scale (CAPS-1), which is a structured interview for
      PTSD, and completed a non-structured clinical interview. The two groups did not
      differ on measured demographic variables, nor were there significant differences
      on self-report or interview measures of anxiety, depression, or PTSD
      symptomatology. Contrary to expectation, groups did not differ on self-report
      measures of dissociation, paranoia, or schizophrenia. African Americans were
      significantly more likely to endorse items of bizarre mentation from the MMPI-2.
      These results suggest that African American and Caucasian veterans with combat
      related PTSD do not differ with regard to manifestation or severity of
      psychopathology.

PMID- 12219338
TI  - Psychoeducation in panic disorder patients: effect of a self-information booklet
      in a randomized, masked-rater study.
AB  - The aim of our study was to evaluate the effectiveness of a self-information
      booklet (SIB) in decreasing anxiety and panic attacks in Panic Disorder (PD)
      patients. Eighty-four patients attending an outpatient clinic due to panic
      disorder were randomly chosen to receive paroxetine with/without a friendly
      designed brochure. Follow-up was done by a masked rater after 1, 3,and 12 weeks
      in order to evaluate whether the co-administration of paroxetine and the brochure
      (Group A) had a beneficial effect over the administration of paroxetine alone
      (Group B). After 3 weeks of therapy, Group A patients had significantly greater
      improvement and lower scores on the Hamilton Anxiety Scale, the Panic Self
      Questionnaire, and the Visual Analog Scale. After 12 weeks, the differential
      improvement was not statistically significant and both groups had improved as
      compared to baseline. The administration of a psychoeducational brochure (SIB) to
      PD patients at the initiation of therapy had beneficial effects during the first
      weeks of treatment. Although this effect fades away, the role of the SIB is
      overstressed in its ability to increase well being and compliance, and reduce
      anxiety and panic attacks.

PMID- 12219339
TI  - Anxiety sensitivity and PTSD among female victims of intimate partner violence.
AB  - The purpose of this study was to evaluate the relationship between anxiety
      sensitivity (AS) and posttraumatic stress disorder (PTSD) in women. The study
      involved three groups: women with no history of exposure to serious trauma (n =
      30), women who had been exposed to intimate partner violence (IPV) but never
      developed PTSD (n = 23), and women with IPV exposure and current PTSD (n = 19).
      As a part of a larger study, they completed measures of AS, PTSD symptomatology,
      and depression. Women with PTSD reported the highest levels of AS, although
      traumatized women with PTSD reported more AS than did women with no trauma
      history. AS-related psychological concerns were a statistical predictor of PTSD
      symptoms when the entire sample of women was considered but not among the subset
      with a trauma history. Nonetheless, AS may be an important factor to consider in
      treatment of individuals with PTSD.

PMID- 12219340
TI  - Is "shy bladder syndrome" a subtype of social anxiety disorder? A survey of
      people with paruresis.
AB  - Paruresis is characterized by the fear of not being able to urinate in public
      bathrooms and has been classified by some to be a sub-type of social anxiety
      disorder (social phobia). Despite the existence of a consumer advocacy
      organization, the "Intentional Paruresis Association (www.paruresis.org)," there
      is sparse literature on this condition. A survey of people affiliated with the
      "International Paruresis Association" was undertaken using a self-report
      questionnaire with items that addressed demographic variables, the phenomenology
      of paruresis, comorbid disorders, and the impact of symptoms on quality of life.
      Sixty-three patients (59 M, 4 F) completed the questionnaire. The mean age of the
      subjects was 38.1+/-12 years, with the mean duration of symptoms being 24.5+/-13
      years. Paruresis impacts significantly on sufferers' lives, with approximately
      one third limiting or avoiding parties, sports events, or dating and just over
      half of the sample limiting the job they choose to do. Social anxiety disorder
      (SAD) and depression are the most common comorbid disorders and the most common
      disorders in family members. Analysis of Liebowitz Social Anxiety Scale (LSAS)
      scores showed higher performance than social interaction subscale scores across
      the whole sample (whether suffering from SAD or not.) However, compared to
      subjects without co-morbid SAD, those with comorbidity had higher total,
      performance, and social interaction scores. Thus, paruresis can be a chronic and
      disabling symptom, and there seems to be an association between paruresis and
      other performance anxieties. Further research to characterize paruresis and to
      determine effective treatments is needed.

PMID- 12219341
TI  - Postnatal skeletal ontogeny in five Xantusiids (squamata: scleroglossa).
AB  - The construction of a comparative database of squamate postnatal skeletal
      development is continued with the detailed description of the mineralization of
      the skeleton from birth to near maximum size in Lepidophyma gaigeae and four
      Xantusia taxa. Observed patterns in the sequence of appearance of epiphyseal
      secondary centers, ossification centers, apophyseal ossifications, and
      calcifications, the distribution of sesamoids, and the timing of fusions are
      compared and contrasted with other squamates. Xantusiids share a similar sequence
      of braincase fusions, but differ in the sequence of appearance of ossification
      centers and epiphyseal secondary centers. Relative to other squamates they
      exhibit an immature neonatal state of ossification, a delayed appearance of
      ossification centers and epiphyseal secondary centers, and an accelerated
      appearance of apophyses. All five xantusiid taxa possess two sesamoids previously
      unreported in squamates. These observations add to the growing body of evidence
      that morphogenesis and osteogenesis are largely independent developmental
      phenomena.

PMID- 12219342
TI  - How do ants stick out their tongues?
AB  - The mouthparts are very important tools for almost any task performed by ants. In
      particular, the labiomaxillary complex is essential for food intake. In the
      present study we investigated the anatomical design of the labiomaxillary complex
      in various ant species, focusing on movement mechanisms. Six labial and six
      maxillary muscles with different functions control the several joints and ensure
      the proper performance of the labiomaxillary complex. According to our
      measurements of sarcomere lengths, muscle fiber lengths and diameters, and the
      relative muscle volumes, the labial and maxillary muscles feature rather slow
      than fast muscle characteristics and do not seem to be specialized for specific
      tasks. Since glossa protractor muscles are absent, the protraction of the glossa,
      the distal end of the labium, is a nonmuscular movement. By histological
      measurements of hemolymph volumes we could exclude a pressure-driven mechanism.
      Additional experiments showed that, upon relaxation of the glossa retractor
      muscles, the glossa protracts elastically. This elastic mechanism possibly sets
      an upper limit to licking frequency, thus influencing food intake rates and
      ultimately foraging behavior. In contrast to many other elastic mechanisms among
      arthropods, glossa protraction in ants is based on a mechanism where elasticity
      works as an actual antagonist to muscles. We compared the design of the
      labiomaxillary complex of ants with that of the honeybee and suggest an elastic
      mechanism for glossa protraction in honeybees as well.

PMID- 12219343
TI  - Muscle development in Antalis entalis (Mollusca, Scaphopoda) and its significance
      for scaphopod relationships.
AB  - We applied fluorescence staining of F-actin, confocal laser scanning microscopy,
      as well as bright-field light microscopy, SEM, and TEM to examine myogenesis in
      larval and early juvenile stages of the tusk-shell, Antalis entalis. Myogenesis
      follows a strict bilaterally symmetrical pattern without special larval muscle
      systems. The paired cephalic and foot retractors appear synchronously in the
      early trochophore-like larva. In late larvae, both retractors form additional
      fibers that project into the anterior region, thus enabling retraction of the
      larval prototroch. These fibers, together with the prototroch, disappear during
      metamorphosis. The anlagen of the putative foot musculature, mantle retractors,
      and buccal musculature are formed in late larval stages. The cephalic captacula
      and their musculature are of postmetamorphic origin. Development of the foot
      musculature is dramatically pronounced after metamorphosis and results in a dense
      muscular grid consisting of outer ring, intermediate diagonal, and inner
      longitudinal fibers. This is in accordance with the proposed function of the foot
      as a burrowing organ based on muscle-antagonistic activity. The existence of a
      distinct pair of cephalic retractors, which is also found in basal gastropods and
      cephalopods, as well as new data on scaphopod shell morphogenesis and recent
      cladistic analyses, indicate that the Scaphopoda may be more closely related to
      the Gastropoda and Cephalopoda than to the Bivalvia.

PMID- 12219344
TI  - Organization of the nervous system in the pygmy cuttlefish, Idiosepius paradoxus
      ortmann (Idiosepiidae, Cephalopoda).
AB  - The idiosepiid cuttlefish is a suitable organism for behavioral, genetic, and
      developmental studies. As morphological bases for these studies, organization of
      the nervous system was examined in Idiosepius paradoxus Ortmann, 1881, using
      Cajal's silver technique and immunohistochemical staining with anti-acetylated
      alpha-tubulin antibody. The nervous architecture is generally identical to that
      described in Sepia and Loligo, but some features characterize the idiosepiid
      nervous system. The olfactory system is highly developed in the optic tract
      region. The dorsolateral lobes show large neuropils, connected with each other by
      a novel well-fasciculated commissure. Each olfactory lobe is subdivided into two
      lobules. The neuropils of the anterior and the posterior chromatophore lobes are
      very poorly developed. Neuronal gigantism is not extensive in the brain; enlarged
      neuronal cells are visible only in the perikaryal layer of the posterior
      subesophageal mass. The giant nerve fiber system is of the Sepia type; the axons
      are not markedly thick and the first-order giant fibers do not fuse with each
      other at the chiasma. Three-dimensional images by whole-mount immunostaining
      clarified the innervation pattern in the peripheral nervous system in detail. Two
      commissural fibers link the left and right posterior funnel nerves ventrally and
      dorsally. The stellate commissure, which is absent in Sepia and Sepiola, connects
      the stellate ganglia with each other. A branch of the visceral nerve innervating
      the median pallial adductor muscle is characteristically thick. Tubulinergic
      reactivity of the cilia and axons reveals the presence of many ciliated cells
      giving off an axon toward brain nerves in the surface of the funnel, head
      integument, arm tips, and epidermal lines. Some of these features seem to reflect
      the inactive nekto-benthic life of the idiosepiid cuttlefish in the eelgrass bed.

PMID- 12219345
TI  - Development of lateral line organs in leptocephali of the freshwater eel Anguilla
      japonica (Teleostei, Anguilliformes).
AB  - A study of the ontogeny of the lateral line system in leptocephali of the
      Japanese eel Anguilla japonica reveals the existence of three morphologically
      different types of lateral line organs. Type I is a novel sensory organ with hair
      cells bearing a single kinocilium, lacking stereocilia, distributed mainly on the
      head of larvae, and morphologically different from typical superficial neuromasts
      of the lateral line system. Its developmental sequence suggests that it may be a
      presumptive canal neuromast. Type II is an ordinary superficial neuromast, common
      in other teleost larvae, which includes presumptive canal neuromasts that first
      appear on the trunk and accessory superficial neuromasts that later appear on the
      head and trunk. Type III is a very unusual neuromast located just behind the
      orbit, close to the otic vesicle, with radially oriented hair cells, suggesting
      that these serve as multiple axes of sensitivity for mechanical stimuli. The
      behavior of larval eels suggests that the radially oriented neuromasts may act as
      the sole mechanosensory organ until the ordinary superficial neuromasts develop.
      The finding that larval eels possess a well-developed mechanosensory system
      suggests the possibility that they are also capable of perceiving weak
      environmental mechanical stimuli, like other teleost larvae.

PMID- 12219346
TI  - Honeycomb structure in the lamina lucida of epidermal basement membrane during
      metamorphosis of Rana temporaria ornativentris.
AB  - In this study we examine the structure of the lamina lucida during metamorphosis
      of Rana temporaria ornativentris. During the metamorphosis of anuran larvae, both
      the epidermal cells and the dermal connective tissues in the tail regenerate. The
      basal surface of the epidermis becomes irregular and the epidermal basement
      membrane detaches from the epidermal cells, showing a widened lamina lucida. In
      this widened lamina we observed a geometrical honeycomb structure and a ladder
      structure. Each side of the honeycomb structure was approximately 40 nm and the
      intervals of the ladder structure were approximately 50 nm. From our observations
      we believe that the honeycomb and ladder appearances are different aspects of the
      same structure. At the beginning of metamorphosis anchoring filaments were
      prominent in the lamina lucida and, when the lamina lucida was tangentially cut,
      the lamina lucida showed the honeycomb structure. These results suggest that both
      the honeycomb and the ladder structures observed in the widened lamina lucida
      originate from constituents of the lamina lucida and become morphologically
      evident during the epidermal-dermal separation.

PMID- 12219347
TI  - Sedation for endoscopy: the safe use of propofol by general practitioners.

PMID- 12219348
TI  - Nurses may be your best tool for improving quality of care.

PMID- 12219350
TI  - ACGME clamps down on hours for residents.

PMID- 12219349
TI  - Quality project improves ventilator weaning.

PMID- 12219351
TI  - Health information disaster planning 101.

PMID- 12219352
TI  - Treatment approach key in diabetes self-management.

PMID- 12219353
TI  - New model integrates DM and CM to boost care for high-risk patients.
AB  - It may seem like an obvious call to provide extensive DM and case management
      services to people who have been deemed "high-risk," but that is typically not
      the rule in the many "high-risk" pools that states have set up for people who
      have been denied commercial insurance elsewhere. However, in an unprecedented
      move, the non-profit insurer for the high-risk pool in Colorado is betting that
      an integrated system of DM and CM services will slash utilization while boosting
      health status. It's an innovative model that could well be replicated if all goes
      as planned.

PMID- 12219354
TI  - Non-traditional approach to pregnancy disease management yields surprising
      outcomes.
AB  - Women with low levels of education and scant financial resources are the hardest
      group to reach with quality prenatal care. As a result, poorer birth outcomes and
      high-cost utilization are difficult to prevent. However, an innovative program in
      Norfolk, VA, that pairs such women with a mentor for guidance and support has
      produced some remarkable results. And as a result, developers are looking to
      duplicate the effort in new areas.

PMID- 12219355
TI  - Pharmacist-driven DM effort relies on predictive data combined with modest
      intervention.
AB  - Given the high number of patients who fail to take their medicines as directed,
      there is a strong case to be made that pharmacists could play a much stronger
      role in DM efforts. Now, Costa Mesa, CA-based Prescription Solutions is testing
      that theory out with two new programs that target high-risk individuals with CHF
      and osteoarthritis. See how the programs combine predictive modeling technology
      with modest telephonic interventions to prevent mildly ill patients from
      deteriorating.

PMID- 12219356
TI  - Face-to-face approach to diabetes DM brings hefty return.

PMID- 12219357
TI  - Pennsylvania data watchdog takes on HMO performance.

PMID- 12219358
TI  - Western NY hospitals and insurers collaborate to form data network.

PMID- 12219360
TI  - Assessment tool generates data to manage patient flow.

PMID- 12219359
TI  - New scoliosis database tracks treatment outcomes.

PMID- 12219361
TI  - [Questions and answers about mandatory reporting of HIV].

PMID- 12219362
TI  - [Systematic followup of the patient living with HIV].

PMID- 12219363
TI  - [From pediatric care centers to adult centers: how to make the transition
      successful?].

PMID- 12219364
TI  - [Towards an integrated network for substance abusers with HIV/AIDS].

PMID- 12219365
TI  - [Bioactive wound dressings].

PMID- 12219367
TI  - [Health system crisis: myth or reality?].

PMID- 12219366
TI  - [Social justice, at the heart of nursing care in AIDS therapy].

PMID- 12219368
TI  - [Curing the health system by democratic dialogue].

PMID- 12219369
TI  - The SIDIIEF and globalization.
AB  - Ah, summer, with its long days, bright colours, fragrances, warmth and wandering
      spirits. Vacations take us away from our usual haunts, sometimes to other lands.
      And on this international theme, I'd like to talk about the Secretariat
      International des Infirmieres et Infirmiers de l'Espace Francophone (SIDIIEF), an
      international association of nurses in the French-speaking world, still quite
      young, that needs your support.

PMID- 12219370
TI  - 'Phantom' provider panels get attention of states, NCQA.

PMID- 12219371
TI  - Compensation monitor. Money isn't everything.

PMID- 12219372
TI  - Has capitation weathered the storm?

PMID- 12219373
TI  - Premium hikes: no cause for celebration.

PMID- 12219374
TI  - Managing the drug benefit: one company's experience.

PMID- 12219375
TI  - Coverage of obesity problematic for most health plans.

PMID- 12219376
TI  - Working too hard, doctor? Poor work flow could be to blame.

PMID- 12219377
TI  - Provider association litigation: better choice for dispute resolution?

PMID- 12219378
TI  - Managed care outlook. Survey predicts more demand for pharmacy precertification.

PMID- 12219380
TI  - [A hospitalized child is a problem of all. Disseminate the Charter of the
      hospitalized child].

PMID- 12219379
TI  - [Techniques to inform and prepare children to various medical and surgical
      procedures by using play].
AB  - To everybody, adult or child, admission to hospital and/or surgery may cause
      concern and fear, because we are afraid of what we do not know. Being informed
      and prepared in a manner appropriate to age and understanding reduces fear and
      distress. Since from their earliest childhood, children learn by play, play in
      its various forms is the best way to inform and prepare them for medical and/or
      surgical procedures. This activity must be carried out by specialists (child life
      specialist, play specialist) who know how to tailor it to the individual needs of
      each patient. Information and preparation are not enough, it is necessary to make
      sure that the message was understood correctly. Since 50% of children go to
      hospital at least once before they are 14, and 2/3 of these cases are taken to
      the Emergency service, a very useful and pleasant form of preventing the trauma
      of hospitalisation is to provide the necessary information about hospital in
      kindergarten and primary school, in a fruitful co-operation among teachers,
      health care professionals and parents.

PMID- 12219381
TI  - [Italian translation and validation of the ICNP Beta (International
      Classification for Nursing Practice].
AB  - The visibility of nursing care can be measured through the results on the patient
      and studying the existing data on patient care. An important area is tied up for
      a common language and terminology because it is important to have a universal
      understanding. For this reason the International Council of Nurses (ICN) has
      elaborated an international terminology for Nursing Practice that can be useful
      to pick up and to catalogue the problems of nursing nature in diagnosis also
      finding a system of classification of the activities The Consociazione
      Association, as representative of the ICN in Italy, through the School of
      Advanced Nursing of the University "La Sapienza" of Rome, has set up a Working
      group for the translation of the document ICNP version Beta. The present article
      explains the difficulties related to the Italian translation, the working group,
      the procedure, the validation and the met problems along with a vision for the
      future development and utilization.

PMID- 12219382
TI  - [The utilization of the ICNP Beta version taxonomy system for the nursing
      protocols' construction].
AB  - The ICNP Beta version system has been used for the revision of hospital protocols
      on the nursing management of the central venous catheters. Despite the taxonomy
      defects of clarity and functionality, our experience has shown an increase of
      understanding and accord between builders professionals and protocol's users.
      Besides all. It has also been important to sensitize the participants to the
      experimentation of an encoded international language.

PMID- 12219383
TI  - [Family nurse: context, conceptual structure and curriculum].

PMID- 12219384
TI  - [Florence Nightingale (May 12, 1820-August 13, 1910)].

PMID- 12219385
TI  - [Strategic planning: integration of training and quality. Experience at the
      Umberto I Polyclinic of Rome].
AB  - This work shows how personnel involvement is one change strategy used in a
      complex organization making use of education and quality as main reorganization
      factors in a hospital system based on old management that didn't consider
      personnel as a strategy resource within a reorganizational change.

PMID- 12219386
TI  - [Use of pharmacological and non-pharmacological techniques to control pain and
      states of suffering].
AB  - In 1993, World Health Organization has assumered pain like pathology and in 1998
      began the spreading of guidelines specifications for cancer pain relief control
      and palliative care in children. Thanks to experience that we acquired in law in
      Oncology and Haematology paediatric Unit of "A. Meyer" Hospital of Florence, we
      have been invited to carry to the last congress of Florence of the AIEOP (Italian
      haematology-oncology paediatric association) an ours contribution in matter. So
      knowing the "state of the art" of the AIEOP centers has become necessary. With
      this work the results of such cognitive investigation will be presented.

PMID- 12219387
TI  - [Traveling the street of "quality accreditation" for nurses].

PMID- 12219388
TI  - [Anxiety and information on heart surgery. A study].
AB  - The heart surgery represents a moment of high critical state for the patient. The
      association of the heart to the idea of the life, intensifies the emotional and
      psychological tensions, the worries for the family, for anaesthesia procedures
      and for the activities developed in the department of intensive therapy. The
      demand of the present study is born on the relationship among information related
      to the principal anxiety elements that the patient meets in intensive therapy and
      the reduction of anxiety in pre and post surgery. Purpose of this study is to
      measure the pre and post surgery anxiety among a group of patients that have
      received a structured information through a brochure on purpose studied and among
      a group of patients that have received not structured information. Results show a
      relationship between information and reduction of patient's heart surgery
      anxiety.

PMID- 12219389
TI  - Self-administration and reuse of medicines.

PMID- 12219390
TI  - Information needs of young people with cystic fibrosis.

PMID- 12219391
TI  - Developing CCN services.

PMID- 12219392
TI  - Supporting families in need.

PMID- 12219393
TI  - Winning arguments on education.

PMID- 12219394
TI  - Chemotherapy-induced nausea and vomiting: a health promotion resource.

PMID- 12219395
TI  - Preceptorship on a Neonatal Intensive Care Unit: evaluating effectiveness.

PMID- 12219396
TI  - The recruitment and retention of children's nurses.

PMID- 12219397
TI  - The value of nursing.

PMID- 12219398
TI  - Shirley Stinson. Interview by Anne J. Davis.

PMID- 12219399
TI  - Privacy of patients in the forensic department of a psychiatric clinic: a
      phenomenological study.
AB  - This study, based on the phenomenological approach, was aimed at exploring the
      meaning of privacy for forensic psychiatric patients. The narratives of two such
      patients, diagnosed with schizophrenia and hospitalized on a forensic unit
      because of a killing offense, were analysed by means of qualitative content
      analysis. The study was conducted in a Swiss psychiatric clinic with forensic
      units. The results demonstrated that 'privacy' is not a question of luxury but a
      very basic human right. The ethical implications for nurses acting as key workers
      in such situations are highlighted. Recommendations for practice are detailed.

PMID- 12219400
TI  - Prisons and prisoners: some observations, comments and ethical reflections based
      on a visit to a prison hospital in the Ukrainian Republic.
AB  - The Republic of the Ukraine has a huge prison population and a large prison
      health care system. Like all other public services in that country it is lacking
      in sufficient funds to operate adequately and with due respect to the human
      rights of the prisoners and its health care employees. This report and
      observations are based on my knowledge of the Ukrainian health care system and a
      visit to a Ukrainian prison hospital. It includes some ethical reflections
      stemming from this experience. Although problem-solving exercises can often help
      to point to areas of potential intervention that could ameliorate a troublesome
      situation, in this case prison health care conditions cannot be substituted for
      economic growth, political stability or increased awareness of societal moral
      obligations.

PMID- 12219401
TI  - Development of a model of moral distress in military nursing.
AB  - The purpose of this article is to describe the development of a model of moral
      distress in military nursing. The model evolved through an analysis of the moral
      distress and military nursing literature, and the analysis of interview data
      obtained from US Army Nurse Corps officers (n = 13). Stories of moral distress (n
      = 10) given by the interview participants identified the process of the moral
      distress experience among military nurses and the dimensions of the military
      nursing moral distress phenomenon. Models of both the process of military nursing
      moral distress and the phenomenon itself are proposed. Recommendations are made
      for the use of the military nursing moral distress models in future research
      studies and in interventions to ameliorate the experience of moral distress in
      crisis military deployments.

PMID- 12219402
TI  - What matters to the parents? A qualitative study of parents' experiences with
      life-and-death decisions concerning their premature infants.
AB  - The aim of this article is to generate knowledge about parents' participation in
      life-and-death decisions concerning their very premature and/or critically ill
      infants in hospital neonatal units. The question is: what are parents' attitudes
      towards their involvement in such decision making? A descriptive study design
      using in-depth interviews was chosen. During the period 1997-2000, 20 qualitative
      interviews with 35 parents of 26 children were carried out. Ten of the infants
      died; 16 were alive at the time of the interview. The comparative method
      (grounded theory) was used to analyse the data. The analysis was carried out
      continuously and in parallel with data collection. Six categories were revealed
      by the analysis: indecision and uncertainty (ambivalence); information and
      communication; participate, but do not decide; seeming to be included; the
      parents' child; and individual consideration. The findings appear to indicate
      that parents agree that they should not have the final word in decisions
      concerning their infants' future life or death. Such a responsibility would put
      too heavy a burden on parents who lack the medical knowledge and the professional
      experience needed to make such a decision, and would be likely to lead to them
      experiencing strong feelings of guilt. The findings show that parents should be
      well informed and listened to during the whole decision-making process. Their
      primary concern was how nurses and physicians communicate with parents who are
      experiencing a crisis, and how this serious information is presented.

PMID- 12219403
TI  - Stories from the operating room: moral dilemmas for nurses.
AB  - This article explores stories related by perioperative nurses when asked to
      describe ethical judgements and subsequent actions that affected patient
      outcomes. A total of 214 patient care situations were analysed for moral actions
      taken and moral outcomes achieved in the perioperative arena. Content analysis of
      the patient care situations revealed a wide variety of ethical issues. Concerns
      about informed consent and quality of care were the most frequently identified
      issues. Respondents reported that 7% of patients underwent unwanted procedures
      and that positive moral outcomes were achieved in 65% of situations. It is of
      concern that, despite the fact that more than two-thirds (69%) of the respondents
      reported undergoing ethics education, only 27% could relate a story of an ethical
      situation.

PMID- 12219405
TI  - HIV/AIDS and professional freedom of expression in Japan.
AB  - A senior physician with a government role in Japan made a widely reported and
      misleading statement about Thailand's policy on HIV/AIDS patients. He claimed
      that in Thailand the policy is to spend public money on the prevention of HIV
      infection while allowing AIDS patients to die untreated. The author, a community
      nursing specialist in Japan with first-hand knowledge of HIV/AIDS policy in
      Thailand, thought that this statement would influence attitudes negatively in
      Japan. However, speaking out about this misrepresentation of the facts carried
      certain risks. Although freedom of expression is valued in Japan, in practice it
      is not easy to contradict senior medical professionals. The author uses his
      experience of this difficult professional situation to teach nurses how to
      approach speaking out in the public interest.

PMID- 12219404
TI  - Confirming older adult patients' views of who they are and would like to be.
AB  - This article reveals a 91-year-old cognitively intact man's lived experiences of
      being cared for in a geriatric context in which the majority of the patients were
      cognitively impaired. A narrative patient story was analysed phenomenologically.
      The findings indicate that this patient's basic needs for ethical care were not
      met. The staff did not see him as a unique individual with his own preferences,
      resources and abilities to master his life. In order to survive this lack of
      ethical care, he played the role of an 'old cognitively impaired man', which
      provided him with at least the understanding and attention the cognitively
      impaired patients received from the staff. The findings also indicate that
      ethical care is independent of whether or not older cognitively intact and
      impaired patients stay or live in the same unit, but it is more dependent on a
      caregiver's ability to respect and confirm each and every patient for who he or
      she is and would like to be.

PMID- 12219406
TI  - Ethical values in health care: an Indian-Swedish co-operation.
AB  - The aim of this report is to present an example of a multidisciplinary Indian
      Swedish co-operation on ethics in health care. It is based on a conference held
      in Asia Plateau, Panchgani, Maharasthra, India in 1998. The emphasis is on
      ethical values that are important for consumers of health care and professionals,
      and also for different cultures in developed and developing countries. The
      importance of human dignity is stressed. Sixteen recommendations are given in an
      appendix.

PMID- 12219407
TI  - The Delta School of Nursing: bioethical nursing education for the Dalit
      ('untouchables') of Tamil-Nadu, India.

PMID- 12219408
TI  - Measuring up.

PMID- 12219409
TI  - On your marks.

PMID- 12219410
TI  - A patient's right to choose.

PMID- 12219411
TI  - The war against disease. Interview by Frances Pickersgill.

PMID- 12219412
TI  - Helping women change their lives.

PMID- 12219413
TI  - Some villagers have never seen a medic. Interview by Colin Parish.

PMID- 12219414
TI  - Facing fear of cancer.

PMID- 12219415
TI  - Bite-sized.

PMID- 12219417
TI  - Clinical accompaniment in community nursing.
AB  - AIM: To investigate student nurses' perceptions of practical accompaniment at
      community health clinics. METHOD: A descriptive study was conducted using a
      convenient sample of third- and fourth-year baccalaureate nursing students. A
      questionnaire was used to gather data from 49 students on their perceptions of
      clinical accompaniment, interpersonal relations with the preceptor and
      educational strategies in clinical teaching. RESULTS: Forty nine students
      returned the completed questionnaires, giving a response rate of 93 per cent.
      Respondents expressed mainly positive feelings on the roles of the preceptor
      during accompaniment. CONCLUSION: There were slight differences in the responses
      given by third-year students and those of fourth-year students. In general,
      students indicated that there was open communication between them and preceptors,
      and that they were satisfied with the educational strategies used by preceptors
      in clinical teaching.

PMID- 12219419
TI  - Diabetic retinopathy.
AB  - The authors describe the serious condition diabetic retinopathy, which can lead
      to blindness. They discuss the nurse's role in caring for patients with this
      condition, as well as in education.

PMID- 12219418
TI  - Iron-deficiency anaemia: developing a nurse-led integrated care pathway.
AB  - Current investigation of asymptomatic iron-deficiency anaemia (IDA) is considered
      incomplete and inappropriate (BSG 2000). Previous investigation has focused on
      specific sinister features, but IDA can be the sole presenting symptom of serious
      underlying pathology and systematic investigation of patients with IDA is of
      prime importance. While participating in a management education scheme by open
      learning (MESOL) in association with the NHS Executive, Open University and
      Institute of Healthcare Management, the author undertook a project to evaluate
      the investigation of IDA within a district general hospital using evolving
      evidence to reconfigure existing services.

PMID- 12219420
TI  - Move to reassure patients after call for staff HIV tests.

PMID- 12219421
TI  - Postnatal care in hospitals: ritual, routine or individualized.
AB  - Postnatal care in hospital continues to include routine recording of observations
      of temperature, pulse, blood pressure, fundal height, lochia and perineal injury
      on clinical pathways that allow little if any leeway for individualizing care.
      This paper discusses the issues of designing a new clinical pathway that
      encompasses best practice, is woman friendly and allows for individualized care
      rather than routine rituals.

PMID- 12219422
TI  - Planned homebirths in Victoria, 1995-1998.
AB  - This paper reports and comments on quantitative aspects of 440 planned homebirths
      attended by registered midwives in Victoria during the three years studied, 1995
      1998. The spontaneous labour rate was 96.4%, and 91.6% of women planning a home
      birth experienced a spontaneous cephalic birth. The overall transfer to hospital
      rate was 20%, the most common reason for transfer being delayed progress in
      labour. 64.2% of women experiencing a vaginal birth had no perineal trauma.
      Postpartum haemorrhage was noted in 5.5% of participants, and 1.1% had a retained
      placenta. Infants were an older gestation and heavier than those in the state in
      general, although the Apgar scores were similar. These data support the claim
      that planned home birth with a qualified midwife remains a demonstrably safe
      option for women who choose this model.

PMID- 12219423
TI  - Midwifery: a profession in transition.
AB  - This study sought to explore midwifery self-identity in relation to two major,
      competing discourses-medicine and midwifery. In-depth interviews were conducted
      with twenty-two midwives working in different settings. Although the study was
      exploratory, the findings showed conclusively that midwifery is not a static,
      discrete body of knowledge (Commonwealth Department of Human Services and Health
      1996); nor should midwifery be seen necessarily falling neatly into one stream or
      another (Davis-Floyd 1992). Rather, midwifery is a discursive practice (Kent
      2000). The midwife (like the obstetrician and nurse) trawls through a range of
      discourses (or ways of understanding and knowing) about the body and childbirth
      in order to construct their own practice. Midwifery is a fluid process of subject
      formation which changes over time according to age; experience; and setting of
      practice (private or public hospital, birth centre or home). Of primary
      significance is the way midwives viewed the body. Few midwives fell into either
      the medical (obstetric assistant) model or the midwifery (professional,
      independent) model. Most midwives could be classified 'hybrid' in the sense that
      their clinical practice drew variously on each of the major discourses according
      to contextual factors.

PMID- 12219424
TI  - The struggles we take for granted in the UK.

PMID- 12219425
TI  - Perineal outcomes in NSW public and private hospitals: analysing recent trends.
AB  - Women using private health insurance for pregnancy care may be unaware of the
      impact that this choice has in increasing their risk of experiencing a range of
      interventions during childbirth. This paper identifies recent trends in
      episiotomy rates and perineal outcomes for New South Wales (NSW) public and
      private hospitals between 1997 and 1999. Clear and consistent differences exist
      in birth outcomes in NSW private hospitals in respect to greater episiotomy use
      and poorer overall perineal outcomes, higher caesarean section rates and higher
      instrumental birth rates. Given the potential health impact for women who
      experience intervention during childbirth, identification of clinically
      unjustified practices is an important step towards ensuring that women's choices
      provide them with optimal childbirth outcomes regardless of their health
      insurance status.

PMID- 12219427
TI  - Graduated compression stockings: updating practice, improving compliance.
AB  - Graduated compression stockings (GCS) have long been used to prevent deep venous
      thrombosis in hospitalized patients. The validation of published research
      findings regarding the use of GCS, and the implementation of practice changes
      pertinent to medical-surgical nursing are examined.

PMID- 12219428
TI  - Conservative management of GERD: a case study.
AB  - Gastroesophageal reflux disease (GERD) is a major problem in primary care. More
      than 25% of the population experience GERD symptoms, and nonerosive forms of the
      disease are common. Conservative management is recommended. This review and case
      study presents conservative treatment options from the updated guidelines for the
      adult patient with GERD.

PMID- 12219429
TI  - Professional nursing portfolios: a global perspective.
AB  - In some countries, nurses develop professional portfolios to obtain or maintain
      licensure, employment, and promotion. A professional portfolio is an important
      marketing tool that enables nurses to demonstrate their competence. Currently,
      regulatory bodies worldwide are considering requirements for portfolio
      development. This global perspective provides information on how to endure a
      professional portfolio.

PMID- 12219430
TI  - Women's decisions regarding management of breast cancer risk.
AB  - Twenty-three unaffected women with a family history of breast or ovarian cancer
      participated in a study to ascertain their cancer-related concerns, beliefs, and
      preferences for risk management. Their perceptions related to breast cancer risk
      management options have implications for practicing nurses.

PMID- 12219431
TI  - Conflict in fiduciary duty involving health care error reporting.
AB  - Fiduciary duty is the responsibility to act in the best interest of a person or
      organization. Health care professionals, as well as managers in other industries,
      struggle continuously with the dilemma of whether or not to admit potentially
      harmful mistakes to unsuspecting customers and patients. Limited public
      disclosure of medical errors will benefit health care staff, organizational
      executives, and patients if specific policies are enacted to improve error
      prevention.

PMID- 12219432
TI  - Smallpox vaccine revisited.

PMID- 12219433
TI  - Initial validation of the perioperative nursing data set in Finland.
AB  - PURPOSE: To explore the relevance of the Perioperative Nursing Data Set (PNDS) in
      Finland. METHODS: A three-round Delphi technique (10 participants) and content
      analysis of 134 articles from the Journal of the Finnish Operating Room Nurses
      Association. FINDINGS: All the PNDS outcomes, 86% of the diagnoses, and 87% of
      the interventions were found to be relevant. The Delphi panel suggested, and
      content analysis revealed, 6 new outcomes, 43 new diagnoses, and 11 new
      interventions. Consensus was achieved on 77%. The phrases used in perioperative
      articles corresponded with those of PNDS 56%-78% of the time. CONCLUSIONS: PNDS
      can be used to describe perioperative nursing in Finland. Further
      conceptualization and validation are needed before using the data set in
      perioperative practice. IMPLICATIONS FOR PRACTICE: Although PNDS cannot be
      implemented in Finland as is, it is a valid structure for further development of
      the terminology, contents, methods, and practice of Finnish perioperative
      documentation.

PMID- 12219435
TI  - President's address.

PMID- 12219434
TI  - Nursing diagnosis and nursing theory: exploration of factors inhibiting and
      supporting simultaneous use.
AB  - PURPOSE: To explore the values and philosophies of nursing theories that inhibit
      the simultaneous use of nursing diagnosis and nursing theory. SOURCES: Published
      articles, books, book chapters. DATA SYNTHESIS: Four factors in the literature
      and reflected in practice may have had a negative influence on the use of nursing
      diagnoses: (a) commitment to the uniqueness of each person, (b) an abandonment of
      the nursing process, (c) a perspective that nursing care is an evolving
      interaction, and (d) a belief that theory-derived language is more articulate and
      precise than standard classifications. PRACTICE IMPLICATIONS: Strategies for
      combining theory and diagnoses include emphasizing the diagnostic terms as
      professional shorthand and permitting flexibility in modifying diagnoses as
      needed; widely disseminating the concept that classification can be used
      effectively with newer iterations of the nursing process reflecting circular,
      simultaneous, and intuitive processes; developing classification language based
      on concepts of hypothesis and perception; and including diagnostic categories
      associated with theoretical perspectives.

PMID- 12219436
TI  - The gender earnings gap in the RN labor market.

PMID- 12219437
TI  - Patient-focused redesign and employee perception of work environment.

PMID- 12219438
TI  - From bedside to board room: interviews with nurse COOs and CEOs (Part II).
      Interview by Alison P. Smith.

PMID- 12219439
TI  - Nurse practitioners and physician assistants in hospital outpatient departments,
      1997-1999.

PMID- 12219441
TI  - Safeguarding patients against medication errors.

PMID- 12219440
TI  - Telephone nursing: client experiences and perceptions.

PMID- 12219442
TI  - Keeping families together.

PMID- 12219443
TI  - Safety in numbers?

PMID- 12219444
TI  - A labour of love.

PMID- 12219445
TI  - Know your true worth.

PMID- 12219446
TI  - Room to improve?

PMID- 12219447
TI  - Stay out of the sun.

PMID- 12219448
TI  - The pharmacist's role in the medicinal management of depression.
AB  - AIM: To elicit pharmacists' perceptions of medication management for people who
      have been prescribed medication for depression. METHOD: A questionnaire survey of
      103 mainly community pharmacists was used. RESULTS: People frequently approached
      pharmacists for information about a range of issues concerning antidepressant
      medication. Although pharmacists were knowledgeable about all aspects of
      pharmacological interventions, many felt their location in the commercial sector
      inhibited the amount of assistance they could provide. Barriers to providing
      information were identified, and the paucity of pharmacists' links with primary
      care teams exposed. CONCLUSION: The survey supports other studies that have
      suggested pharmacists could provide considerable assistance in helping people to
      understand their medication and its benefits. There is also discussion of the
      ways in which the future role of pharmacists could be developed so that they
      collaborate more closely with other healthcare professionals.

PMID- 12219449
TI  - The nurse practitioner's role in day case pre-operative assessment.
AB  - This article discusses the benefits of developing a nurse practitioner role in
      day case surgery through an appropriate education programme and a
      multidisciplinary support group. The authors found that the expanded role can
      work well in this setting and benefit patients.

PMID- 12219450
TI  - Assessing acutely ill patients on general wards.
AB  - The recent increase in demand for intensive care facilities has resulted in a
      growing number of patients experiencing periods of critical illness in acute ward
      areas (Murch and Warren 2001). The authors of this article provide a structured
      system of assessment for nurses to assess acutely ill patients in the general
      ward environment.

PMID- 12219451
TI  - Myalgic encephalomyelitis. Gold standard care.

PMID- 12219452
TI  - Outlook: scattered strokes.

PMID- 12219453
TI  - Should I stay or should I go?

PMID- 12219454
TI  - I quit because it's an impossible task.

PMID- 12219455
TI  - Training tool that's a livin' doll.

PMID- 12219456
TI  - What is malaria?

PMID- 12219457
TI  - Teenage pregnancy: whose problem?

PMID- 12219458
TI  - The language of chest pain.

PMID- 12219459
TI  - Women patients' views of secure psychiatric services.

PMID- 12219460
TI  - Cardiopulmonary resuscitation. Tracheal intubation--3. Post-intubation checks and
      management.

PMID- 12219462
TI  - Nurses' hidden work.

PMID- 12219461
TI  - Developing a multidisciplinary continence service.

PMID- 12219463
TI  - Patients' experiences of clean intermittent catheterisation.

PMID- 12219465
TI  - Spinal injury and bowel management.

PMID- 12219464
TI  - An overview of skin care and faecal incontinence.

PMID- 12219466
TI  - Day in the life.

PMID- 12219467
TI  - The sharp end of psychiatry.

PMID- 12219468
TI  - [Obesity is dangerous--but what effects does weight loss have?].

PMID- 12219469
TI  - [The MRSA threat also in the region of Stockholm. Shortages when it comes to
      hygienic routines must be take care of].

PMID- 12219470
TI  - [Alarming signals concerning the increasing antibiotic resistance].

PMID- 12219471
TI  - [The SBU on overweight and obesity: Huge increase of overweight-related
      diseases].

PMID- 12219472
TI  - [Age-related macular degeneration--new possibilities for prophylactic measures].
AB  - Age-related macular degeneration (AMD) is the most common cause of severely
      reduced vision in the Western World. The only treatment method previously
      available, thermal laser photocoagulation of choroidal neovascularization (CNV),
      has considerable limitations. More recently, new methods for prophylactic
      measures and therapy have been developed. A randomised pilot study has shown that
      prophylactic laser treatment of soft drusen maculopathy reduced the risk of
      exudative AMD significantly. Larger studies are in progress. A randomised and
      placebo controlled study of 3.600 patients for six years showed recently that a
      combination of antioxidants and zinc reduced the risk of severe AMD in patients
      with soft drusen maculopathy by 25%. Large, randomised and placebo controlled
      studies showed that photodynamic treatment of certain forms of CNV significantly
      reduced the risk of severe vision loss. Other methods, such as transpupillary
      thermotherapy, surgical treatment and pharmacological treatment are being further
      developed. Visual rehabilitation, using eccentric viewing, has been found
      successful.

PMID- 12219473
TI  - [How an outbreak of MRSA in Gothenburg was eliminated: by strict hygienic
      routines and massive control-culture program].
AB  - The largest single-strain outbreak of methicillin resistant Staphylococcus aureus
      (MRSA) in Scandinavia so far occurred at Sahlgrenska University Hospital in
      Western Sweden 1997-2000. The strain identified was identical to the UK EMRSA-16
      strain. 147 patients at 36 different wards became colonised or infected.
      Established routines for infection control had to be revised. The endemic
      situation necessitated an MRSA screening programme in October 1999 for all former
      hospital patients on re-admission. Since May 2000 no patient has been found with
      the outbreak strain at Sahlgrenska University Hospital.

PMID- 12219474
TI  - [The physiopathological mechanisms behind chronic myofacial pain].
AB  - Chronic orofacial myalgia is characterized by muscle pain, tenderness, stiffness,
      and restricted range of mandibular movement. It can be localized and due to
      temporomandibular disorders, or part of a generalized myalgia, e.g. fibromyalgia.
      The etiology and pathophysiology are unclear, but it is reasonable to assume that
      both peripheral and central mechanisms take part. Peripheral sensitization by
      serotonin and other mediators is a possible mechanism behind the development and
      modulation of chronic myalgia, while amplification of pain due to central
      sensitization in conjunction with disordered antinociception may represent the
      mechanisms for the maintenance of pain. Central sensitization seems to involve
      wind-up phenomena due to activation of N-methyl-D-aspartate receptors located on
      second-order neurons in the brainstem. Derangements in descending endogenous pain
      modulating systems due to central serotonin deficiency may explain the disordered
      antinociception.

PMID- 12219475
TI  - [Every tenth hospitalized patient is given antibiotics for a nosocomial
      infection].
AB  - In a point-prevalence survey at Huddinge University Hospital, Sweden, 237/723
      (33%) of patients admitted to non-psychiatric units received antibiotics. Among
      these, 181 received treatment for an infection and 56 as prophylaxis. We found
      that 11% of all patients were treated with antibiotics for a nosocomial infection
      and that an additional 8% received antibiotics as prophylaxis for nosocomial
      infections. The high rate of infections emphasizes the importance of integrating
      surveillance of nosocomial infections into the quality system.

PMID- 12219476
TI  - [Species-specific face recognition].

PMID- 12219477
TI  - [A surgical technician in Mozambique is not tired in spite of being on call every
      day].

PMID- 12219478
TI  - [Is early invasive treatment in acute coronary syndromes necessary? Suggestions
      to alternative interpretation of the FRISC II study].

PMID- 12219479
TI  - [Who can rely on the National Board of Health and Welfare?].

PMID- 12219480
TI  - [Serious factual errors in the TV show "Kalla fakta"].

PMID- 12219481
TI  - [Insufficient credibility of tobacco industry].

PMID- 12219482
TI  - [Environmental tobacco smoke is carcinogenic].

PMID- 12219483
TI  - [Editors' views concerning the proposal on ethical scrutiny of research].

PMID- 12219484
TI  - [Estrogen, B12 and aging].

PMID- 12219485
TI  - [The beginning of human development from the embryological viewpoint].
AB  - Human development commences with a fertilisation cascade, initiated when the
      haploid chromosomes of the oocyte and the sperm unite, thereby forming a
      programme for the creation of a human being. During the first few days
      development proceeds to implantation and placentation in only 30% of cases. The
      frailty of this early development shows that a human blastocyst, should it manage
      to emerge from the zygote, will only succeed in turning into a human being if
      there is a maternal contribution to implantation and placenta formation. The
      obstacles to early development represent basic genetic and epigenetic phenomena
      within the cytoplasm and in the genome of the blastomeres and are the results of
      the operation of natural laws the exact causal concatenations of which remain yet
      to be determined in detail by science. Philosophers, ethicists and lawyers seem
      to have difficulties in accepting that more research in this field is required.
      Finally, a look at the legal protection of the human embryo in Germany reveals
      that the earliest stage of human development prior to implantation is legally
      protected in vitro, whereas there is no such legal protection in vivo, owing to
      Germany's abortion law (StGB (German Penal Code) section 218), before
      implantation. Aspects of the research on human embryos and embryonic stem cells
      are here discussed from this point of view.

PMID- 12219486
TI  - [Genetic view of the development of the human embryo--the importance of
      chromosome abnormalities].
AB  - Normal embryonic and fetal development requires a diploid chromosome set
      consisting of a haploid maternal and a haploid paternal chromosome set.
      Chromosome abnormalities in the zygote are not a rare event, however. Moreover
      postzygotically different types of aberrations can occur, with different effects
      on embryonic development. As a consequence embryonic development can be arrested
      at a very early stage. Other consequences are the impairment of the implantation
      rate, early spontaneous abortions and developmental abnormalities in newborn
      children. The results of the analysis of the chromosomal constitution of early
      embryos show the impact of specific chromosome abnormalities on embryonic
      development. Normal development on the basis of a normal chromosome set seems to
      be only one of several possible developments after fertilization.

PMID- 12219487
TI  - [Performance of in vitro fertilization in Germany].
AB  - In Germany the application of assisted reproductive techniques (ART) is regulated
      by federal legislation. Compared with the international situation the "German
      Embryo Protection Law" is very "restrictive" and various methods of ART are
      prohibited, e.g. oocyte/embryo donation, embryo cryopreservation and
      Preimplantation Genetic Diagnosis (PGD). Furthermore, in Germany only 1 to 3
      fertilized oocytes may be cultured to embryo. All these embryos then have to be
      transferred into the uterus of a particular patient. Additional fertilized
      oocytes can only be cryopreserved in a pronuclear state. The success rate of ART
      has increased significantly over the past few years owing to the introduction of
      blastocyst cultures and the selection of 1 to 2 good quality blastocysts for
      embryo transfer. Furthermore, the transfer of only 1 to 2 blastocysts effectively
      reduces the risk of high rank multiple pregnancies. In Germany, however, the
      selection of only a few good quality blastocysts for transfer is prohibited by
      law. New laboratory techniques, e.g. pronuclear scoring and polar body biopsy
      screening for aneuploidy are in accordance with German law. The application of
      these methods provides a selection of "good quality oocytes" and seems to
      increase the overall success rate. Further studies are required, however. The
      success rate, quality and cost effectiveness of ART in Germany appears
      compromised when compared with many other countries. What is more, in contrast to
      the international situation research and development in ART in Germany has been
      decreasing constantly over the past few years, due to the inappropriate
      regulations of the German health care system and the insufficient support given
      to university-based centers.

PMID- 12219489
TI  - [Changes of the German embryo protection law from a physician's point of view].
AB  - It is a legitimate question to ask of reproductive medicine, whether it does meet
      the actual nedds of the people involved. Although te conveying of information and
      counselling has been much improved, there are still deficiencies. Artificial
      insemination (for lesbian couples also) should be based on a solid juridical
      foundation to allow more appropriate counselling to be provided. As studies on
      parents and procreated children after egg donation have shown that there are no
      developmental abnormalities, it appears that the prohibition  of oocyte donation
      is outdated. Preimplantation genetic diagnosis (PGD), human embryo selection and
      research on the human embryo  will continue tobe issues that lead to controversy
      laden ethical discussions. Ideas on the graded protection of human life might lay
      the foundation for a pragmatic consensus for further discussions.

PMID- 12219488
TI  - [Reproductive medicine--the state of the law].
AB  - Reproductive Medicine is subject to a large number of legal regulations.
      Professional law, public law, civil law and criminal law hold several special
      regulations in store for this particular area. This article gives a brief
      overview of the regulations applicable to reproductive medicine. Special problems
      that demand legislative action are pointed out.

PMID- 12219490
TI  - [Comparisons of legal conditions for reproductive medicine in Germany with other
      European states and the need for reform that emerges].
AB  - This article gives an overview of the rules and principles established in Germany
      with regard to reproductive medicine. In addition the article outlines the
      respective rules that exist in western European states and investigates the
      bioethics principles established by the Council of Europe and the UNESCO.
      Compared with those of the western European states the German rules are rigid,
      restrictive and conservative. Because in an open international society the more
      liberal approaches will prevail, it will not be possible, in the long run, to
      uphold the distinctions made by the German rules.

PMID- 12219491
TI  - [Right and ethics in reproductive medicine--medical and ethical aspects].
AB  - Legality and ethics in reproductive medicine are interdependent. Whether ethics
      degenerates into an ethics of convenience and adaptation, or into an ethics that
      always comes too late, depends on each doctor and researcher. Our medical care
      requires legal guidelines. There is not only a responsibility for research, but
      also one for engaging in research. This position is presented in four sections:
      on reproductive medicine, the moral status of the embryo, the research on spare
      embryos and in a section on reproductive medicine in Europe.

PMID- 12219492
TI  - [Preimplantation versus prenatal diagnosis--a comparison from the human genetics
      point of view].
AB  - This articles compares the most common techniques for prenatal diagnosis,
      amniocentesis and chorionic-villus sampling, with pre-implantation genetic
      diagnostics (PGD) with respect to the underlying indications, methodological
      aspects and safety. A major new indication for PGD in assisted reproduction is
      aneuploidy testing, which aims at transferring euploid embryos and increasing the
      pregnancy rate. The importance of adequate genetic counselling prior to PGD is
      stressed.

PMID- 12219493
TI  - [Preimplantation versus prenatal diagnosis--practice of prenatal diagnosis].
AB  - Both invasive and non-invasive prenatal medicinal procedures are well accepted in
      Germany. The health care system offers each pregnant woman a total of three
      sonographic examinations. Most of these examinations turn up normal findings,
      leading to the pregnancy being continued without fear. In the case of anomalies
      being detected, the findings may be life-saving for the mother or the foetus or
      reduce the severity of a neonatal disease. When a severe anomaly or a situation
      that is incompatible with postnatal life is detected, the pregnant woman may
      decide not to go through with the pregnancy. The latter state of affairs is the
      reason for 2% of all terminations of pregnancies. One of the aims of modern
      prenatal medicine is to provide information about whether a situation is normal
      or abnormal as soon as possible ("early anomaly scan", "nuchal translucency
      diagnostics"). In view of this background it is difficult to understand why the
      very small number of women with a high risk of a recurrence of severe anomalies
      diagnosable by PGD is not given access to this method but is forced to terminate
      their pregnancies in the event of an anomaly during their second trimester.

PMID- 12219494
TI  - [Is preimplantation diagnosis legal?--on the need for harmonizing legislation].
AB  - Whether PGD is already legally permitted in Germany today is a moot point. A
      guidelines draft of the Germany's Federal General Medical Council, the
      Bundesarztekammer, on pre-implantation genetic diagnostics that--like the earlier
      findings of the ethics commission of the German federal state of the Rhineland
      Palatinate--assumed that the method is admissible, if certain clearly-defined
      indications are present and a rigorous testing procedure has been established,
      has given the discussion a new impetus. The discussion is in full swing, with
      calls by politicians for the legislator to pass a regulation mounting. Of late,
      though, constitutional objections have been raised against a positive-law
      regulation. Such a simple legal move to regulate PGD, it is claimed, would
      violate the constitutionally-guaranteed right to inviolable human dignity.
      Critics, however, point out that such an absolute inviolability does not exist.
      According to them, not only the verdicts by the German Federal Constitutional
      Court, the Bundesverfassungsgericht, on the reform of section 218 of the German
      Federal Penal Code (StGB)--the paragraph that specifies the conditions under
      which an abortion is not punished--that relativize (in terms of the indication
      model) one claim to existence with respect to another, but also the approval in
      terms of pharmaceutical and medicine-products law of nidation-blocking agents,
      serve to show this. If the condition of being a human being were made to coincide
      with the completion of the genetic code upon the completion of the process of
      fertilisation, then one tended to forget, the critics noted, that this attendant
      dignity was not properly "infused with life" unless nidation had been successful.
      Without nidation everything were fragmentary, the total protection of human
      dignity according to Article 1 Section 1 of the Federal Republic's Basic Law,
      Germany's constitution, notwithstanding. During every in vitro fertilisation
      embryo transfer is conditional upon a variety of factors the presence of which is
      not noted until after fertilisation has taken place. On the part of the embryos,
      too, certain conditions have to be met whose presence at the moment of
      fertilisation is not assured. Thus an embryo with, for instance, defects that can
      be visually detected will not be transferred. With regard to these facts too the
      opponents of pre-implantation genetic diagnostics must be challenged to answer
      the question of why an embryo with visually-detectable defects should undoubtedly
      be allowed to be discarded, but the act of searching for "internal" defects be
      banned. Thus the fact remains that the mere acceptance of the loss of created
      embryos does not make artificial insemination a punishable offense, as long as
      the motive for the act is to bring about pregnancy. To achieve legal security for
      the couples and the physicians involved the law on the protection of embryos
      should be changed. The new regulations should determine under which conditions
      PGD is permissible. As is already the case for other norms that apply to
      reproductive medicine, but also for the practice of abortion, these regulations
      should contain an analogous right of refusal for the professionals involved. The
      laws relating to the healing professions, to the professional chambers, as well
      as the regulations of the various German federal states (which together
      constitute the Federal Republic of Germany) that apply to the professions should
      be amended accordingly.

PMID- 12219495
TI  - [Doubts about preimplantation diagnosis].
AB  - Pre-implantation genetic diagnosis (PGD) allows physicians engaged in
      reproductive medicine, in the course of complying with the desire of prospective
      parents for healthy offspring, to examine the embryo prior to its intra-uterine
      transfer for genetic defects, which might otherwise lead to grave afflictions,
      and according to the results of the examination to either implant the embryo in
      the mother's womb or to discard it. Rather than being sanctioned by the laws
      applying to the profession (Vow, section 14 MuBO) this procedure is subject to
      penalty (section 1 Section 1 Subsection 2, section 2 Section 1). Moreover, it
      violates the basic rights of the embryo. Thus, according to the constitutional
      and criminal law still in force, as well as the current legal standards of the
      medical profession, PGD is prohibited in Germany.

PMID- 12219496
TI  - [The child as damage--physicians' liability in cases involving reproductive and
      prenatal medicine].
AB  - In case of medical malpractice courts grant the parents of unwanted or
      handicapped children damages towards the costs of alimony. In this article the
      development of the courts' rulings and the criticism made of them will be
      presented in detail. Granting damages towards the costs of alimony does not call
      into question the right to live of an unborn child. It is rather just another
      case of professional liability of physicians. Regarding the development of the
      law, with respect to the legal admissibility of induced abortions, including
      those undertaken during late stages of pregnancy, the physician may come under
      pressure to recommend an abortion to rule out any claims for damages. This
      subject is in need of legal regulation pursuant to the forthcoming medical
      reproduction law.

PMID- 12219497
TI  - [Pregnancy termination in which the child would have been able to survive].
AB  - The reform of paragraph 218 (dealing with abortion) of the German Penal Code has
      caused the formerly embryopathic grounds for abortion to be subsumed within the
      medical grounds for abortion. This has led to the temporal limit on those cases
      in which a pregnancy is terminated on medical grounds due to foetal malformation
      to fall away. This state of affairs must be rated differently with respect to
      children with grave defects not able to survive and those with minor defects who
      would be able to survive. In the latter cases a regulation on a time limit or
      limits that took account of the ability of the unborn child to survive is called
      for. In addition, in the case of children that would have been able to survive
      feticide by injection of medication is recommended.

PMID- 12219498
TI  - [Application of stem cell technology and nuclear transfer in animal models].
AB  - Pluripotent embryonic stem (ES) cells established from undifferentiated cells of
      early embryos together with embryonic germ (EG) cells derived from primordial
      germ cells are used for gene transfer into the germ lines of mice. ES cells are
      also capable of in vitro differentiation into embryo-like aggregates (embryoid
      bodies) consisting of meso-, ecto- and endodermal cells. Except in chicken in no
      other vertebrate species pluripotent cell lines equivalent to murine ES cells are
      established. Recently, isolated human pluripotent cells originating from spare
      IVF embryos or aborted human foetuses have successfully been differentiated into
      somatic cells and may at some point serve as cellular grafts for transplantation.
      In therapeutic cloning somatic cells can be reprogrammed by fusion with an
      enucleated oocyte. Later the established autologous ES cells from the resulting
      nuclear transfer embryo can be differentiated into the specific cell type needed
      for tissue therapy.

PMID- 12219500
TI  - [Therapeutic and reproductive cloning from a legal point of view].
AB  - The German constitution contains no easy answers to the question of whether and
      under what circumstances an altering of the current embryo protection law might
      lead to the therapeutic or even reproductive cloning of human beings being
      allowed. Due to the fact that guiding fundamental research does not exist, the
      time for a decision has surely not yet come. But should concrete opportunities
      for therapy based on therapeutic cloning begin to emerge or it become clear that
      reproductively cloned humans are not genetically disadvantaged when compared with
      human beings engendered through impregnation (an unrealistic prospect from a
      present-day perspective), then the legislator himself will have to come to a
      decision, openly and by taking a balanced account of his social responsibilities.
      Hiding behind the constitution by, for instance, simply alluding to human dignity
      will then no longer be an option.

PMID- 12219499
TI  - [Differentiation potential of human stem cells--approaches to tissue engineering
      and to cell transplantation].
AB  - The prospect of future clinical applications of human stem cells is one of the
      major arguments for the use of embryonic stem cells. Scientists are currently
      developing methods to culture and isolate different somatic cell types. The
      enormous capacity for proliferation of embryonic and certain adult stem cells
      combined with suitable protocols to differentiate these cells may allow the
      production of sufficient amounts even of those cell types which cannot be
      expanded in the terminal differentiated state. The ability to generate large
      quantities of certain somatic cells in vitro has led to the first cell
      transplantation-based therapeutic concepts and clinical studies. Even today
      comparatively simply structured in vitro-engineered tissues are applied
      clinically. However, to grow larger and more complex structures, a variety of
      problems including their vascularisation and the development of suitable matrices
      have to be resolved. In the long term, tissue engineering offers an as yet
      incalculable potential for future medical applications and may finally allow the
      development and clinical transplantation of complex tissues or even whole organs.

PMID- 12219501
TI  - [Therapeutic and reproductive cloning--remarks for the point of view of medical
      ethics and anthropology].
AB  - Cloning may be done for scientific, therapeutic or reproductive purposes. Whereas
      these purposes are ethically speaking considered beneficial, the opinions on the
      protection of the embryo and the protection of possible future children are
      highly controversial. Arguing upon a background of anthropological insights, the
      role of nature and the aim of medical intervention, the significance of the non
      disposability of initial and developmental conditions for human freedom and the
      equality of and between humans is investigated.

PMID- 12219502
TI  - [Change in reproductive behavior in Germany compared with the rest of Europe].
AB  - When the processes involved in the decline of the birth rate are analysed very
      often no distinction is made between voluntary and involuntary childlessness. The
      article presents a comparative overview of the international development of
      fertility and highlights the consequences of this development in Europe. In the
      second part of this article the development of the birth rate in Germany and its
      consequences are discussed.

PMID- 12219504
TI  - [Point of view of the inquiry commission on correctness and ethics in modern
      medicine].

PMID- 12219503
TI  - [The current state of law as a mirror of social movements and currents].
AB  - The question of what movements and currents in society may have urged the
      legislator to grant to the life of the pre-implanted embryo complete legal
      protection, in obvious contradistinction to the total denial of the latter to a
      post-implantation foetus, when a pregnant woman is deem to be in a legally
      recognised pregnancy-related conflict situation, is investigated. To the extent
      that it exacerbates the difficulties of sterile couples to have children, this
      state of affairs differs considerably from the legal situation of almost all
      other countries of the western world. It is dismaying to note the widespread lack
      of interest of the public regarding the question of how to bridge the
      inconsistencies of evaluation of the need for protection of human life before and
      after nidation. Arguments designed to explain this discrepancy in legal or
      ethical terms do not convince. Apart from the lessening impact of the role of
      women in reproduction, it is the awareness of the historic burden of national
      guilt created by the atrocities committed by the Third Reich that is said to
      account for the scrupulousness and backward as opposed to prospective orientation
      of large parts of German society. Sterile women and couples are those that suffer
      most on account of this situation and might ultimately be tempted to look for
      medical help in more liberal countries, should their wish to have children be
      thwarted in Germany for legal reasons.

PMID- 12219506
TI  - Blood shot.

PMID- 12219505
TI  - Weighing up direct entry.

PMID- 12219507
TI  - Under cover.

PMID- 12219508
TI  - Hit the spot.

PMID- 12219509
TI  - Handle with care.

PMID- 12219510
TI  - Calling the tune.

PMID- 12219511
TI  - Recognising heart failure.

PMID- 12219512
TI  - Involving patients in teaching about blood-borne viruses.
AB  - Involving patients in the teaching of healthcare staff is not a new concept, but
      there is a shortage of literature on the subject. This article focuses on the
      experiences of staff on an established education and training programme for HIV
      and other blood-borne viruses. The programme involved four patients in the
      teaching of nurses and other health and social care staff. This article describes
      the recruitment, preparation and methods used, as well as the possibilities of
      transferring the methodology to other subject areas. The author concludes that
      there are advantages and disadvantages to be considered before embarking on such
      a programme.

PMID- 12219513
TI  - Managing patients with a tracheostomy in acute care.
AB  - Most acute wards occasionally receive patients with tracheostomies, but
      relatively infrequent experience of caring for these patients means that nurses
      have limited opportunities to practise their knowledge and skills. This article
      examines the indications for using a tracheostomy and provides a problem-centred
      approach to patient care.

PMID- 12219514
TI  - The tissue viability society.

PMID- 12219515
TI  - Adverse reactions to wound dressings.
AB  - This article describes the potential risks to patients' skin from the use of
      wound dressings and how to minimise those risks. Guidance is provided on the
      steps to be taken once an allergic reaction is suspected.

PMID- 12219516
TI  - Risk assessment and prevention audit project.
AB  - This article describes the aims and objectives of a small pilot audit project to
      evaluate the impact of guideline recommendations to reduce pressure ulcer
      development on practice and patient care.

PMID- 12219517
TI  - The role of the nurse in wound bed preparation.
AB  - This article explores the role of the nurse in wound bed preparation. Wounds
      cannot be tended to in isolation--many patient factors will influence healing.
      The nurse needs to have an understanding of the process of wound healing and have
      undertaken a full patient assessment before focusing on the patient's wound.
      Recognising and managing problems at the wound bed, for example necrotic tissue
      and excess exudate, can result in a better prepared wound bed and optimal
      healing. If the concept is to be valuable to nurses, they need to be part of the
      debate that defines wound bed preparation, how it is being implemented in
      clinical practice and how patients can benefit. This debate needs to include all
      nurses involved in wound care.

PMID- 12219518
TI  - What's working? Finding solutions that attract and keep nursing staff.

PMID- 12219519
TI  - Beyond setup: preference cards as a tool for managing in the OR.

PMID- 12219521
TI  - Keeping employees happy in tough times.

PMID- 12219522
TI  - Should we build an MIS operating room?

PMID- 12219523
TI  - Patients have right to an interpreter.

PMID- 12219524
TI  - Obesity surgery in an ASC with extended stay.

PMID- 12219525
TI  - Competing by design.

PMID- 12219526
TI  - Mindful over mindless: learning to think like an entrepreneur.

PMID- 12219527
TI  - Setting the stage for innovative action.
AB  - Consider the steps you need to take to introduce innovative thinking into your
      organization. It's a combination of free-flowing process, managerial support and
      individual creativity.

PMID- 12219528
TI  - Physician executives share insights on ways to influence people.

PMID- 12219529
TI  - Physician to two presidents avoids politics, prefers adventure.

PMID- 12219530
TI  - Involving medical staff in strategic decisions is key to success.

PMID- 12219531
TI  - U.S. health care in conflict--Part I. The challenges of balancing cost, quality
      and access.
AB  - Grappling with a technology explosion, an aging population and a growing number
      of uninsured, our health care system faces an uncertain and troubling future.
      Examine the critical issues influencing health care policy development and think
      about ways to address the dilemma of balancing cost, quality and access.

PMID- 12219532
TI  - Everything I needed to know about medical management I learned in acting school.
AB  - Some people are doctors. Some people play them on TV. Brian Meltzer could
      probably do both. A physician executive at Memorial Sloan-Kettering Cancer
      Center, Meltzer relies on skills he learned in acting school to help manage
      business decisions. In the first of several essays for The Physician Executive,
      Meltzer explains how acting can help you become a better leader.

PMID- 12219533
TI  - Bountiful health care and A Beautiful Mind.
AB  - The Nash Equilibrium (put forward by John Nash and celebrated in the film, A
      Beautiful Mind) mathematically describes multi-player, infinite games. It is a
      general description of large human transactions, such as health care. Learn how
      new inputs, new players or new resources can disrupt these transactions.

PMID- 12219534
TI  - Strategies to boost your income, enhance your bottom line.

PMID- 12219535
TI  - How much is your practice worth?--Part I.

PMID- 12219536
TI  - Patient privacy: a policy shift.

PMID- 12219537
TI  - D for desperate.

PMID- 12219538
TI  - No luxuries.

PMID- 12219539
TI  - Shoulder high.

PMID- 12219540
TI  - Return to Ethiopia.

PMID- 12219541
TI  - Political persuasion.

PMID- 12219542
TI  - Living with ignorance.

PMID- 12219543
TI  - An end to 'them and us'.

PMID- 12219544
TI  - Healthy profit.

PMID- 12219545
TI  - Inside knowledge: issues in insider research.
AB  - Insider research, that is, conducting research in an organisation or culture to
      which the researcher belongs, poses specific problems for the design and conduct
      of a research study. In particular, researchers need to take account of the
      influence their connection with the culture has on the results and how they are
      interpreted. Benefits of this research approach include collecting in-depth data
      on the subject. In a personal account of her experiences of insider research, the
      author identifies some of these issues and makes suggestions about how they can
      be resolved.

PMID- 12219546
TI  - Integrated care pathways for patients with complex needs.
AB  - This article describes a process to improve documentation for older, severely
      mentally ill, patients on a continuing assessment unit, the initial problems
      encountered and the eventual benefits.

PMID- 12219547
TI  - The individual with epilepsy.
AB  - Epilepsy is a global condition, affecting at least 50 million people (Reynolds
      2001). Judith Lanfear provides an overview of the classification, treatment and
      management of epilepsy, as well as examining the social impact of living with
      this condition.

PMID- 12219548
TI  - A world of difference.

PMID- 12219549
TI  - The quality of nursing home care in Taiwan.
AB  - This study describes the quality of care in nursing homes in Taiwan using
      demographic data, functional status measures, resident clinical care outcomes,
      and resident's ratings of satisfaction with nursing home care. Three hundred and
      eight randomly selected elderly residents in 13 nursing homes were interviewed
      through a structured interview process and demographic and medical information
      was collected from their nursing home records. Nursing home residents were
      younger and less functional than their counterparts in the United States. Stroke
      and dementia were the most common primary diagnoses and more than 27% of the
      residents had a history of urinary tract infections while more than 25% had been
      physically restrained within the past 3 months. There was no correlation between
      the number of nursing home staff per resident and the prevalence of selected
      clinical care outcomes. A moderate level of satisfaction with nursing home care
      was reported with acceptance of family visits and nursing home cleanliness rating
      highest, and loss of personal belongings and life as boring rating lowest. Level
      of satisfaction with nursing home care was positively correlated with the number
      of RNs and nursing assistants (NAs) on staff. Recommendations for improving the
      quality of nursing home care in Taiwan include increased recruitment of
      multidisciplinary professional and technical nursing home staff; restrictions in
      the use of restraints with development of alternatives; and use of standardized
      resident assessment, care planning, and evaluation tools. The authors recommend
      continuing education in geriatric nursing and continued nursing research focusing
      on identifying structure and process variables that affect clinical care outcomes
      and satisfaction with nursing home care.

PMID- 12219550
TI  - Driving over 65: proceed with caution.
AB  - The issue of driving in the elderly population will continue to be relevant for
      public discourse. Because the termination of driving may be seen as an end of
      independence, it is important to appreciate that it has both emotional and
      pragmatic consequence. Senescence includes a host of physiological changes that
      may influence one's driving ability. Yet, aging alone does not infer poor driving
      ability. Health care providers should encourage and support the development of
      accurate methods of evaluation for older drivers and discuss adaptive strategies
      with older drivers in an effort to maintain their independence while promoting
      public safety.

PMID- 12219551
TI  - Older adults with hip fractures. Treatment of pain following hospitalization.
AB  - This study examined pain experiences and treatment for older adults in long-term
      care or rehabilitation settings 3 week after surgical repair of a hip fracture.
      Pain report and pain treatment for cognitively intact residents were compared
      with cognitively impaired residents. Two thirds of all participants reported
      pain. Most rated pain as slight or mild in severity. Pain report was similar for
      cognitively impaired and intact participants. Pain was reported as severe or
      worse by 17% of the residents. Nursing care plans documented comfort as a goal
      for fewer than half the participants. Almost 40% (n = 23) of the participants
      were receiving no pain medication 3 weeks postoperatively, five of these rated
      their pain as moderate or severe. Pain documentation, including effective non
      pharmacological treatments, needs to be improved for cognitively impaired and
      intact older adults who are recovering from hip fracture surgery.

PMID- 12219552
TI  - Reminiscence group activities and discourse interaction in Alzheimer's disease.
AB  - Reminiscence is an enriching and complex experience having many purposes and
      functions when used with patients with Alzheimer's disease (AD). Discourse is a
      component of language that has been shown to decline in patients with AD (Mentis,
      Briggs-Whittaker, & Gramigna, 1995). This article represents one of the first
      studies to examine the effects of reminiscence group (RG) activities on discourse
      interactions in patients with AD. This article specifically addresses the AD
      population within a RG setting. Observations suggested that objective ratings of
      conversational discourse would be better (less impaired) in patients with AD when
      obtained in relatively unstructured environments (e.g., during RG activity) as
      compared to ratings obtained in conversational environments imposing more
      structure (e.g., a session in which language function was being evaluated).
      Comparisons made of conversational and narrative discourse skills observed during
      different testing environments in patients with AD revealed predicted outcomes.
      That is, discourse elicited in an environment that was less structured yielded
      qualitatively better discourse patterns, particularly related to selecting and
      maintaining a topic, requesting additional information about a topic, changing a
      topic during conversation, and turn-taking. Results are discussed in terms of
      their relevance to gerontological nurses managing patients with AD.

PMID- 12219553
TI  - Nurses' and family members'. Perceptions of nursing home residents' needs.
AB  - The purpose of this study was to determine the degree of agreement between
      nursing home staff and families in assessing the needs of cognitively impaired
      nursing home residents. A convenience sample of 36 family members of nursing home
      residents with cognitive impairment and the nurses assigned to those patients was
      recruited from three nursing homes. The Nurse and Resident Perceptions
      Questionnaire, adapted from Lindgren and Linton (1991), was used to assess
      functioning in activities of daily living, physiologic, and psychosocial areas.
      Significant differences were found for eight items of physiologic and
      psychosocial functioning: difficulties with chewing, swelling of feet, orthopnea,
      weakness, easy bruising, recognition of people, lack of privacy, and boredom.
      Nurses rated all these areas less problematic than did the family members.
      Collaborative efforts of family members and nurses are needed to develop
      effective plans of care for these problems of nursing home residents with
      cognitive impairment.

PMID- 12219554
TI  - Illiteracy: a silent disability.

PMID- 12219555
TI  - New checklist for pressure ulcer prevention.

PMID- 12219556
TI  - A speedy approval.

PMID- 12219557
TI  - Circle of suspicion.

PMID- 12219558
TI  - Body parts gone bad.

PMID- 12219559
TI  - Hoaxes: supreme fakers. The doctor's got your goat. In the 1920s, a testicle
      transplant was a 'cure' for impotence.

PMID- 12219561
TI  - The value of pharmaceuticals--some direction for employers.
AB  - The costs of drugs keep rising. Are they worth it? Employers should consider
      value over cost, and make decisions based on diagnostics and research. They
      should thoroughly examine their organizations' experience to determine high
      priority health conditions and do cost-effectiveness studies (using experienced
      consultants if necessary) that focus on all of the consequences of conditions and
      indicate the best medical and pharmaceutical therapies to treat them. Doing so
      should produce both human and financial dividends.

PMID- 12219560
TI  - Meet the missing link (wink, wink).

PMID- 12219562
TI  - Managing pharmacy benefits cost-effectively for an aging workforce.
AB  - Many baby boomers believe age is no more than a number. Employers and plan
      sponsors will need to provide cost-effective pharmacy benefits to this group, as
      well as other Americans, all of whom will be using more prescriptions that cost
      more. Employers and union trusts can use a pharmacy benefits management (PBM)
      company that understands the importance of cost management, focuses on improving
      patient outcomes and works with the plan sponsor to create a phased approach to a
      disciplined pharmacy management strategy. Education of all parties is key.

PMID- 12219564
TI  - Value propositions in future pharmaceutical benefits.
AB  - Within this decade, benefit managers will see radically new diagnostics and drugs
      that will call for changes in drug benefit planning. This article provides
      insight into various value propositions that must be taken into account in a drug
      benefit plan, along with considerations integral to those propositions; some key
      trends; and the new drug pipeline. Benefit managers must remain aware of the drug
      pipeline and benefit trends and utilize the insight of peers or other experts in
      strategic benefit planning.

PMID- 12219563
TI  - Pharmacy discount card programs: catching up with the health markets.
AB  - Pharmacy costs continue to rise, as does the number of senior citizens. One of
      the ways of containing costs may be the pharmacy discount drug card program, for
      both seniors and the general population.

PMID- 12219565
TI  - Retiree health coverage.
AB  - This article reviews a number of issues that affect retiree medical coverage as
      part of a multiemployer trust. Strategies for both short- and long-term planning
      to ensure economic viability of the retiree medical plan include overcoming
      myths, obtaining data and doing the math, being realistic, minimizing political
      issues, communication and education. The resolution of issues and problems should
      always be a part of a strategic planning process rather than dealt with on an
      emergency or quick fix basis.

PMID- 12219566
TI  - The Privacy Rule: HIPAA standards for the privacy of individually identifiable
      health information.
AB  - The main objective of the HIPAA Privacy Rule is to provide a uniform and
      simplified minimum standard for the privacy of individually identifiable health
      information. Five broad categories are covered: boundaries, security, consumer
      control, accountability and public responsibility. Compliance with the Privacy
      Rule includes appointing a security official, making some basic assessments about
      a fund's current policies and procedures, assessing security protocols for
      network systems, developing a participant complaint mechanism and creating an
      internal grievance procedure for employer action and employee whistle-blowing. At
      this writing, although the final standards are still under debate, most health
      care plans should accept the regulation and begin compliance procedures.
      Successful implementation of the Privacy Rule can streamline fund operations and
      give participants the added security and peace of mind they demand.

PMID- 12219568
TI  - Loophole tied to bizarre case.

PMID- 12219567
TI  - New leadership group comes under fire from ACHE board. Position paper calls
      organization duplicative, says its premise overlooks issue of funding for
      training.

PMID- 12219569
TI  - Third time a harm? Anthem may raise premiums for third straight year, outraging
      Maine consumers.

PMID- 12219570
TI  - Hours of doctors-in-training: who's counting? ACGME's restrictions limiting
      residents' workhours denounced as inadequate.

PMID- 12219571
TI  - The best things in life are free. 2 Vermount hospitals abandon JACAHO
      accreditation.

PMID- 12219572
TI  - First things first. Medicare must be fixed before adding a hugely expensive drug
      benefit.

PMID- 12219573
TI  - In need of repairs. Litigation alleges operational, accounting defects at
      equipment maintenance firm Neodyme, in bankruptcy protection since March.

PMID- 12219574
TI  - The price of privacy. Historic patient privacy regulations win immediate praise
      from hospital lobby, but political ripples show debate is far from over.
AB  - The final patient privacy regulations published last week in the Federal Register
      won immediate praise from the healthcare lobby. Providers now have the guidance
      they have been waiting for to prepare for a crucial compliance deadline. But the
      industry's stance may lead to a public relations nightmare down the road, as it
      places them in opposition to patient advocates and some lawmakers.

PMID- 12219575
TI  - 'We're not in crisis mode'.

PMID- 12219576
TI  - Paging Doctor Phil.

PMID- 12219578
TI  - Progress towards poliomyelitis eradication: Afghanistan and Pakistan--January
      2000 to April 2002.

PMID- 12219577
TI  - Outbreak of diarrheal illness in attendees at a Ukrainian dance festival,
      Dauphin, Manitoba--May 2001.

PMID- 12219579
TI  - Sonolysis of synthetic sediment particles: particle characteristics affecting
      particle dissolution and size reduction.
AB  - The effect of ultrasound on particle shape and surface structure was explored to
      understand particle characteristics affecting contaminant desorption and
      destruction from sediment particles. Compared to only hydrodynamic mixing, in the
      presence of an ultrasonic probe, operating at 20 kHz with a power density of 460
      Wl-1, sonication decreased the particle size of alumina and silica particles
      following a first-order regime. In addition, the dissolution of particles during
      sonication is 7-20 times higher than that of non-sonicated solutions. However,
      the decrease of particle size was not totally explained by dissolution. Scanning
      electron microscopy studies showed that the surface of particles both became
      smoothed and pitted as a result of sonication. Therefore, it seems that multiple
      mechanisms are occurring simultaneously; microstreaming acts to smooth particle
      surfaces and dissolve particles and shockwaves and microjets imploding on the
      particle surfaces both shear and pit the surface of the particles. The sonication
      of humic acid laden particles resulted in a similar decreasing trend. However,
      the existence of humic acid increased the complexity of the system.

PMID- 12219580
TI  - Design and calibration of a single-transducer variable-frequency sonication
      system.
AB  - The design of a novel single-transducer variable-frequency sonication system
      capable of operating at constant acoustic power over the range 20-500 kHz is
      described. The system employs a mass-loaded sandwich transducer arrangement and a
      series of transformers to provide an accurate impedance matching circuit.
      Approximately 0-5 W of acoustic power are produced by the system at typical
      operating frequencies of 20, 40, 150, 200, 300, and 450 kHz. As a first test of
      the single-transducer variable-sonication system we have re-examined the
      frequency dependence of the sonochemical oxidation of potassium iodide. Previous
      investigators have monitored the frequency dependence using a multi-transducer
      system to obtain the different frequencies required. In accordance with the
      earlier findings, we have observed an eightfold increase in the rate of potassium
      iodide oxidation at 300 kHz compared to 20 kHz, as well as an inversion in the
      rate of oxidation for argon and air-saturated solutions at 300 kHz. Possible
      reasons for the rate variations are discussed.

PMID- 12219581
TI  - Effects of dissolved gases and an echo contrast agent on ultrasound mediated in
      vitro gene transfection.
AB  - The effects of acoustic cavitation on in vitro transfection by ultrasound were
      investigated. HeLa cells were exposed to 1.0 MHz continuous ultrasound in culture
      media containing the luciferase gene. Transfection efficiency was elevated when
      an echo contrast agent, Levovist was added or air was dissolved in the medium.
      When cells were sonicated in medium saturated with Ar, N2 or N2O which have
      different gamma values (Cp/Cv), or were saturated with He, Ar or Ne with
      different thermal conductivities, the effectiveness for the dissolved gases in
      the ultrasound mediated transfection was Ar > N2 > N2O or Ar > Ne > He,
      respectively. When free radical formation in water by ultrasound was monitored as
      a measure of inertial cavitation, it was similarly affected by dissolved gases.
      These results indicate that the efficiency of ultrasound mediated transfection
      was significantly affected either by occurrence of or by modification of inertial
      cavitation due to various gases.

PMID- 12219582
TI  - Ultrasonic acceleration of iodination of unactivated aliphatic hydrocarbons.
AB  - Iodination of unactivated aliphatic hydrocarbons with iodoform (CHI3) and solid
      NaOH were greatly accelerated under ultrasonic irradiation. The mechanism of the
      sonochemical acceleration was studied.

PMID- 12219583
TI  - Sonolysis of surfactants in aqueous solutions: an accumulation of solute in the
      interfacial region of the cavitation bubbles.
AB  - The sonolysis of surfactants (such as sodium dodecylbenzenesulfonate (DBS),
      sodium dodecylsulfate (SDS), and polyethylene glycol monostearate), sodium 4
      toluenesulfonate (STS), and 1-hexanol in aqueous solutions was investigated under
      an argon atmosphere with ultrasound of 200 kHz in order to compare the scavenging
      efficiency of the hydroxyl radical and the accumulation in the gas-liquid
      interfacial region of the cavitation bubbles. The degradation rate of the solute
      follows the order 1-hexanol > DBS and SDS > STS. The scavenging efficiency of the
      hydroxyl radical by non-volatile surfactants was much greater than that of the
      non-volatile and hydrophilic solute (e.g., STS). The surfactant was accumulated
      in a relatively high ratio in the interfacial region. The degradation of
      surfactants occurred by reaction with the hydroxyl radical and also by pyrolysis
      at high temperature. On the other hand, STS, due to its non-volatile and
      hydrophilic properties, was principally present in the bulk solution and the
      degradation by pyrolysis was not observed at the investigated concentration
      ranges.

PMID- 12219584
TI  - Complex particles produced from graphite powder by acoustic cavitation in water.
AB  - Spaghetti-like structures made of fibers whose diameter are of about 1-2 microns,
      straight structures from about 10-20 microns and optically semitransparent
      particles, with linear dimension up to about 0.3 mm, were obtained from fine
      graphite powder in water subjected for 20 h to acoustic cavitation at a frequency
      of 19.5 kHz. A picture of spaghetti-like structures obtained by scanning electron
      microscopy is reported. From X-ray diffraction pattern, it was found that the
      semitransparent precipitates have an amorphous nature.

PMID- 12219585
TI  - Improvement of an ultrasound assisted method for the analysis of total
      carbohydrate in environmental and food samples.
AB  - The determination of the carbohydrate content of environmental and food samples,
      performed by spectroscopic and chromatographic methods, needs a preliminary
      hydrolysis which converts polysaccharides into monosaccharides prior to the
      analytical measurement. In this paper, a modified procedure of the ultrasound
      assisted method for the determination of total carbohydrates, published by the
      same authors in a previous paper, is presented and discussed. The modified
      procedure represents an improvement with respect to the previous one because it
      shortens the hydrolysis time and the colorimetric determination times through the
      use of two acid media (formic and acetic acid) that also allows quantitative
      recoveries of total carbohydrates from food and environmental samples.

PMID- 12219586
TI  - Effect of ultrasound on the extractibility of corn bran hemicelluloses.
AB  - Various two-step extraction procedures with and without a short application of
      ultrasound in the first step were used to examine the effect of sonication on the
      extractibility and properties of the non-cellulose components of industrial corn
      bran (CB). The polysaccharides recovered from the extracts of the first (FI) and
      second (FII) extraction step were characterised by yield and composition. Using
      water as extractant in the first step, similar yields of total extracted
      polysaccharides (FI + FII) were obtained by the short sonication treatment when
      compared to the classical procedures using H2O2-containing alkaline media in the
      first step. The yields of FI + FII showed a substantial increase (10-40%) after
      application of ultrasound in 1% and 5% NaOH in comparison to those of the
      classical procedures. The content of the neutral sugar components constituting
      the CB xylan varied from 65 to 88 mol% in dependence on the conditions used in
      the first extraction step.

PMID- 12219587
TI  - Supplementary statement for the 2002-2003 influenza season: update on oculo
      respiratory syndrome in association with influenza vaccination.

PMID- 12219588
TI  - ORS during the 2000-2001 influenza vaccination season.

PMID- 12219589
TI  - Following nurses' orders. At N.J. hospital, doctors agree to take cues from
      advanced-practice nurses. The program is leading to better quality, increased
      revenue.

PMID- 12219590
TI  - 100 most powerful.
AB  - Compiling a list of the 100 Most Powerful People in Healthcare requires some
      contemplation. Exactly what is power in this industry? C. Thomas Smith, president
      and CEO of VHA, calls power simply "the ability to make a difference." The
      influential figures chosen by Modern Healthcare readers represent a broadly
      varied and diverse group of movers and shakers. But they share the ability to
      change things.

PMID- 12219591
TI  - Healthcare fraud probes have hospitals ahead of the game.

PMID- 12219592
TI  - AHA's profits take tumble.

PMID- 12219593
TI  - [Limited relevance of veterinary disciplinary regulations].
AB  - After several years of pressure on the part of the KNMvD to establish
      disciplinary regulations for veterinarians, these were at last incorporated in
      the Veterinary Practice Act of 1992. This article discusses the extent to which
      veterinary disciplinary regulations actually meet the expectations of
      legislators. On the basis of an investigation of the parliamentary passage of the
      Act, the flood of complaints before disciplinary judges, the nature and magnitude
      of jurisprudence of the veterinary disciplinary committee, and interviews with
      those involved, it would appear that results are disappointing. These
      disappointing results, in particular the one-sided emphasis on companion animals
      and the continuing misunderstanding about the prescription of veterinary
      medicines, lead to the conclusion that veterinary disciplinary regulations are
      currently of limited relevance. The authors consider that insufficient use is
      made of the potential of disciplinary measures to contribute to the monitoring of
      the quality of veterinary practice and give recommendations about this.

PMID- 12219595
TI  - [Plasma T4-concentration and plasma TSH-concentration important parameters for
      diagnosis of hypothyroidism in dogs].

PMID- 12219594
TI  - [The economical future of the modern companion animal practice].

PMID- 12219596
TI  - [Veterinary disciplinary law. It is written and printed...].

PMID- 12219597
TI  - [CED is now called 'Veterinary quality organ'].

PMID- 12219599
TI  - [FIDIN antibiotics report 2001. Put together by the FIDIN Working Group for
      Antibiotic Management, June 2002, The Hague].

PMID- 12219598
TI  - [Farmers' survey causes lots of talk].

PMID- 12219600
TI  - [Boundary between allowable and non-allowable practices of veterinary medicine
      not sharper].

PMID- 12219601
TI  - [Poisoning by Senecio].

PMID- 12219602
TI  - [Diagnostic related groups interfere with effective pain therapy. Must your
      patients clench their teeth?].

PMID- 12219603
TI  - [Infection--20 times more frequent than AIDS].

PMID- 12219604
TI  - [Defibrillator in the gambling casino?].

PMID- 12219605
TI  - [Preventing stroke. Which antihypertensive drugs can do it better?].

PMID- 12219606
TI  - [After discontinuation of the Women's Health Initiative Study of hormone
      substitution. Should hormone replacement be stopped? (interview by Dr. Brigitte
      Moreano)].

PMID- 12219607
TI  - [ICD-10 primary health care. WHO support for family practice psychotherapy].
AB  - In the year 2001, The World Health Organization (WHO) published a special edition
      of the International Classification of Mental Disorders (ICD-10, Chapter F) for
      use by general practitioners (ICD-10 PHC-Primary Health Care). In this GP version
      of the ICD-10, diagnostic categorizations and algorithms serving treatment
      requirements are summarized in simplified form. Unlike the general ICD-10
      guidelines, this version also contains management guidelines for each disease
      category. These include information for the patient and family, advice on
      counseling, description of treatment methods, and indications for specialist
      referral. The treatment guidelines are differentiated, concrete and suitable for
      use in the doctor's office, and concise (in each case not more than a single
      page). The WHO also offers an education program to enable the interested GP to
      deepen his knowledge of the treatment guidelines and their theoretical basis. A
      particular feature of this program are patient information leaflets that guide
      the physician on what the patient needs to be told. The physician can use these
      as a basis for his talks with the patient, or give them to the patient for home
      study.

PMID- 12219608
TI  - [Confrontation instead of avoidance. Why anxiety patients should face the
      causes].
AB  - Psychiatric management forms the basis of any integrated psychiatric treatment.
      It serves to maximize the patient's level of performance, safety and quality of
      life. It also involves the patient's family members--who are usually indirectly
      affected by the disorder and may provide support during the course of treatment-
      in the therapeutic strategy. The psychiatric management of anxiety disorders can
      be effectively carried out, also by the family doctor familiar with mental
      disorders, since the GP is usually the first primary care instance to be
      approached by the patient, who assumes an underlying organic cause rather than a
      mental problem. Within the framework of psychiatric management, the family doctor
      should be kept fully informed of the individual steps in the treatment strategy,
      and coordinate the necessary interventions by other care providers. By taking
      psychoeducative measures he can already initiate effective treatment, and may
      create a positive atmosphere in which treatment-requiring anxiety can be openly
      discussed and perhaps partly resolved. Talking to the patient about early
      symptoms may help to avoid severe relapses. Psychiatric management as part of the
      general practitioner's activities helps achieve the goal of integrating the
      treatment of patients with anxiety disorders in the doctor's office.

PMID- 12219609
TI  - [Managing depressed patients in family practice. Helping the patient out of the
      emotional pit, without personally falling in].
AB  - Some 10-15% of all patients consulting the general practitioner have depressive
      disorders. Both depressive episodes and dysthymic disorders often have a
      considerable negative impact on quality of life and occupational performance.
      This also applies to the course of somatic diseases, and such disorders are a
      risk factor for the development of chronicity and may negatively affect
      compliance. In the treatment of depressive patients, the GP benefits from his
      experience in the treatment of chronically ill patients and his case management
      skills. Treatment of depressive disorders is effected in three phases: acute
      treatment, maintenance treatment, relapse prevention. During these phases,
      typical problems jeopardizing the success of treatment may occur, such as the re
      appearance of psychopathological symptoms, or even emotional problems on the part
      of the careprovider himself.

PMID- 12219610
TI  - [Acute aortic syndrome. A thoracic emergency--unfortunately with a large
      selection of symptoms].
AB  - Acute aortic arch syndrome is a medical emergency associated with a high
      mortality rate. In view of the great variation in symptomatology, this condition
      can readily be overlooked. A carefully obtained history (pain!), a thorough
      physical examination (differences in pulse and blood pressure) may be suspicious
      for acute aortic arch syndrome, which today can be reliably and rapidly diagnosed
      by noninvasive imaging (CT, TEE). Confirmation of the suspected diagnosis must be
      followed by further intensive medical surveillance (Stanford B) or, in the event
      of involvement of the ascending aorta or aortic arch (Stanford A), referral
      without delay to a cardiosurgical center. Apart from a further shortening of the
      time lapse between diagnosis establishment and emergency surgery, new therapeutic
      (e.g. stenting) and surgical procedures may improve the prognosis of the
      syndrome. Maybe new diagnostic tools (monoclonal antibodies against aortic myosin
      and radio-immunoscintigraphy) will help to recognize the aortic syndrome more
      rapidly.

PMID- 12219611
TI  - [Drug therapy of heart failure. Don't wait until the legs swell].

PMID- 12219612
TI  - [Crescendo or decrescendo principle? Pain therapy in osteoporosis].

PMID- 12219613
TI  - [Mobility and quality of life for arthrosis and rheumatism patients. Modern pain
      management with selective cox-2 inhibition].

PMID- 12219614
TI  - [Rapid and safe pain management. Promising new cyclooxygenase inhibitor].

PMID- 12219615
TI  - [Despite antihypertensive medication every 4th patient has elevated blood
      pressure values in the morning].

PMID- 12219616
TI  - [Pain therapy. Exaggerated anxiety regarding opioid administration].

PMID- 12219617
TI  - [Painless and tissue sparing. Insulin injection without needle].

PMID- 12219618
TI  - [Depression: St. John's wort is only effective after 2 to 3 weeks. Initial phase
      can be bridged with baldrian].

PMID- 12219619
TI  - [Phosphodiesterase inhibitor for erectile dysfunction. No less effective in the
      diabetic patient].

PMID- 12219620
TI  - [Pulse pressure indicates risk. Systolic hypertension is especially dangerous].

PMID- 12219621
TI  - [Diabetes therapy. Blood vessel oriented rather than glucose-centered].

PMID- 12219622
TI  - [Essential basics in therapy of heart failure. Without diuretics the prognosis is
      poor].

PMID- 12219623
TI  - [34. Acute and chronic renal failure--prognosis depends on early diagnosis!].

PMID- 12219624
TI  - [New aspects of arthrosis research].

PMID- 12219625
TI  - [Recommendations of EULAR on treatment of gonarthrosis. Report of a committee of
      the "Standing Committee for International Clinical Studies Including Therapeutic
      Trials (ESCIST)"].
AB  - BACKGROUND: Osteoarthritis (OA) is the most common joint disease encountered
      throughout Europe. A task force for the EULAR standing committee for clinical
      trials met in 1998 to determine the methodological and logistical approach
      required for the development of evidence-based guidelines for treatment of knee
      OA. The guidelines were restricted to cover all currently available therapies for
      knee OA diagnosed either clinically and/or radiographically affecting any
      compartment of the knee. METHODS: The first stage was the selection of treatment
      modalities to be considered. The second stage comprised a search of the
      electronic databases Medline and Embase using a combination of subject headings
      and key words. All European language publications in the form of systematic
      reviews, meta-analyses, randomized-controlled trials, controlled trials and
      observational studies were included. During stage three all of the relevant
      studies were quality scored. The summary statistics for validated outcome
      measures, when available, were recorded and where practical the numbers needed to
      treat (NNT) and the effect size (ES) for each therapy was calculated. The fourth
      stage involved determination of key clinical propositions by expert consensus
      employing a Delphi approach. The final stage involved ranking of these
      propositions according to the available evidence. A second set of propositions
      relating to a future research agenda was determined by expert consensus using a
      Delphi approach. RESULTS: Over 2400 English language publications and 400 non
      English language publications were identified. Seven hundred and forty four
      studies presented outcome data of the effects of specific treatments on knee OA.
      Quantitative analysis of treatment effect was possible in only 61 studies.
      Recommendations for the management of knee OA based on currently available data
      and expert opinion are presented. Proposals for a future research agenda are
      highlighted. CONCLUSIONS: These are the first clinical guidelines on knee OA to
      combine an evidence-based approach and a consensus approach across a wide range
      of treatment modalities. It is apparent that only certain clinical propositions
      are supported by substantial research-based evidence, while others are not. There
      is thus an urgent need for future well designed trials to address key clinical
      questions.

PMID- 12219626
TI  - [Clinical epidemiology of hip and knee joint arthroses: an overview of the
      results of the "Ulm Osteoarthrosis Study"].
AB  - AIM OF STUDY: To summarize the strategy of patient recruitment, applied methods
      and published results within the Ulm Osteoarthritis Study, a multicenter cross
      sectional survey of patients with advanced hip and knee osteoarthritis. METHODS:
      420 patients with hip OA and 398 patients with knee OA scheduled for unilateral
      total joint replacement in four hospitals in the southwestern part of Germany
      underwent detailed clinical investigations and a standardized interview in
      addition to radiographic analyses of ipsilateral and contralateral hip or knee
      joint and both hands. Odds ratios and 95% confidence intervals for the
      association of different possible risk factors with OA patterns (unilateral,
      bilateral and generalized OA) were calculated with logistic regression, adjusting
      for potential confounders. RESULTS: In 41.7% of patients with hip OA and 33.4% of
      patients with knee OA, an underlying pathological condition allowed a
      classification as secondary OA. 82.1% of patients with hip and 87.4% of patients
      with knee OA had bilateral disease. Generalized OA (GOA) was found in 19.3 and
      34.9%, respectively (after adjustment for different age and sex distribution in
      the two patient groups; however, this difference was not any more significant). A
      positive association could be observed between hypercholesterolemia and GOA in
      knee OA patients as well as between serum uric acid and GOA in hip OA patients.
      Obesity and overweight were associated with bilateral knee OA, but not bilateral
      hip OA nor GOA. DISCUSSION: Our innovative study design allows the non-invasive
      investigation of patient subgroups with established disease and a testing of
      relevant hypotheses in an appropriate setting. The data add to the evidence
      regarding the independent role of different systemic risk factors for OA. In an
      ongoing study the natural course of the disease of the contralateral, unoperated
      joint is currently being investigated in all recruited patients.

PMID- 12219627
TI  - [Quantitative cartilage analysis with magnetic resonance tomography (qMRI)--a new
      era in arthrosis diagnosis?].
AB  - Magnetic resonance imaging (MRI) is a new and very powerful method for the
      diagnostics and monitoring of osteoarthritis. Its advantage is that all articular
      tissues can be visualized directly and are accessible for three-dimensional
      analysis. This article reviews qualitative, semi-quantitative, and quantitative
      studies on articular cartilage with MRI. In particular we discuss pulse sequences
      and three-dimensional postprocessing methods for quantitative analysis of
      cartilage volume and thickness, along with their accuracy and precision in
      healthy volunteers and patients with osteoarthritis. It addition, we present
      approaches for quantitative analyses of structural/biochemical parameters and for
      the deformational behavior of cartilage in vivo.

PMID- 12219630
TI  - [Status of arthrosis research in Germany].

PMID- 12219631
TI  - [Retained and discontinued conventional and unconventional measures by patients
      with Bechterew disease for modifying the course of illness].
AB  - BACKGROUND: Patients with chronic rheumatic disease often seek relief in
      unconventional treatments, but many of them do not share this information with
      their physician. OBJECTIVE: To explore which conventional and unconventional
      interventions are used by patients with ankylosing spondylitis. Which of these do
      they continue to use and which do they give up? PATIENTS: One-hundred fifty
      patients (36 female, 114 male) with ankylosing spondylitis, who presented for
      radon thermal treatment at the Gasteiner Heilstollen Hospital (mean age 50 +/- 11
      years; disease duration 24 +/- 11 years). METHOD: A previous investigation
      identified 75 interventions used by patients with AS to influence their disease.
      In a face-to-face, structured interview all these interventions (terms used by
      the patients) were now presented to 150 other patients with AS. They were asked
      to state whether they had already used (and given up) the respective intervention
      or whether they intend to continue using it and intend to use it in future.
      RESULTS: A summary of all interventions previously and still used by patients
      showed conventional interventions (67%) to out-number unconventional (33%)
      interventions. Of the 150 patients, 20 stated that they use or have used more
      than 15 different unconventional interventions. In addition to health resort
      medicine (interview at a health resort!), massage therapy, physiotherapy and
      physical exercise were the most commonly used of the conventional interventions.
      Of the unconventional interventions warm climate, sea bathing, self-applied
      psychotherapy, vitamin pills, repression, showering with alternating cold and
      warm water, and self-help groups were named most frequently. CONCLUSION: Some
      patients with ankylosing spondylitis use many different (33% unconventional)
      interventions. In the patient's view, even rather general interventions such as
      warm climate or sea bathing are regarded as relevant to the disease. An open
      doctor-patient discussion of unconventional interventions used by the patient
      appears reasonable. The results confirm that most patients suffering from chronic
      and incurable disease seek relief in unconventional therapies.

PMID- 12219632
TI  - [Technique and value of arthrosonography in rheumatologic diagnosis--3:
      Ultrasound diagnosis of the ankle joint, foot and toes].
AB  - The clinical investigation of ankles, feet, and toes is frequently equivocal in
      rheumatology. Sonography can distinguish between underlying pathologies. We
      suggest following standard scans: 1) anterior longitudinal scan to diagnose
      effusions in the ankle and talonavicular joints, to display erosive and
      osteoarthrotic pathologies, and to diagnose tenosynovitis of the extensor
      tendons; 2) anterior transverse scan to document the findings in an additional
      dimension; 3) lateral transverse scan and 4) lateral longitudinal scan to
      diagnose tenosynovitis of the peroneus tendons; 5) medial transverse scan and 6)
      medial longitudinal scan to diagnose tenosynovitis of the flexor tendons; 7)
      posterior longitudinal scan and 8) posterior transverse scan to evaluate the
      Achilles tendon, the retrocalcaneal bursa, and the posterior recess of the ankle
      joint. Additionally we suggest optional scans: 9) plantar longitudinal scan for
      the plantar fascia and the plantar calcaneal surface; 10) distal anterior
      longitudinal scan to evaluate the midtalar joints; 11) distal anterior
      longitudinal scan to evaluate the toes; and 12) plantar, distal transverse scan
      to evaluate the flexor tendons of the toes. Additionally, the correlating
      longitudinal and transverse scans can be used to confirm the findings. The
      frequency of the transducer should be about 7.5 MHz for ankles and the peroneus,
      flexor, and extensor tendons. Ten to over 20 MHz are possible for more
      superficially located structures. Using modern equipment with higher resolution a
      hypoechoic border may be normal up to 3 mm in the ankle joints, the MTP joints,
      and around the peroneus tendons, and up to 4 mm around the tibialis posterior
      tendons.

PMID- 12219633
TI  - [External inter-facility evaluation of rheumatologic acute care clinics].

PMID- 12219634
TI  - [Treatment costs and case reimbursement comparison of rheumatology clinics].

PMID- 12219635
TI  - [Data collection and appraisal of outcome quality in the rheumatology acute
      hospital].

PMID- 12219636
TI  - [Diagnosis and therapy of nodular tenosynovitis of the tendon sheath--case
      presentation].
AB  - A well-localized nodular mass near on a tendon is often the first clinical sign
      of a nodular tenosynovitis or so-called tenosynovial giant cell tumor of the
      tendon sheath. We report three cases of this rare tumor localized at the lower
      extremity, in correlation with clinical, radiographic and intraoperative
      findings. After the pathologic diagnosis was made, the patient in the first case
      decided not to have the tumor resected. This patient's postoperative course
      continues uneventfully without expansion of the tumor. In the second and third
      case, a surgical intervation was performed but both developed a local recurrence.
      A second operation with partial resection of the tendon was successfully
      performed. To the last follow-up 12 and 24 months after revisions, there were no
      signs of local recurrence. The review of the literature shows that treatment
      modalities for such lesions range from excisional biopsy to radiation therapy.
      The authors present their own experience with the MRI diagnosis and the therapy.
      Using well-defined histopathologic criteria, marginal resection is the treatment
      of choice. To prevent a local recurrence, partial resection of the tendon should
      be done during the primary surgery.

PMID- 12219637
TI  - [Anti-Sm antibodies--marker antibodies in systemic lupus erythematosus (SLE)].

PMID- 12219638
TI  - [2 years data of controlled trials with leflunomide vs. methotrexate and
      leflunomide vs. sulfasalazine].

PMID- 12219639
TI  - [Rheumatology coding guideline. A guideline for clinical practice].

PMID- 12219640
TI  - [Do arthralgia and arthritis manifest during or after an infection with
      Erysipelothrix rhusiopathiae (erysipelas)].

PMID- 12219641
TI  - [Modern intracranial pressure measurement techniques].

PMID- 12219642
TI  - [Modern intracranial pressure measurement techniques. Basic principles and
      general practice].
AB  - Measurement of intracranial pressure (ICP) has to be regarded as a standard
      procedure in today's treatment of severe head-injured patients. Intraventricular
      or intraparenchymal measurement should be used. The essential value for intensive
      care treatment is the cerebral perfusion pressure (CPP). Its value should be kept
      strictly > 70 mmHg. Computer-based analysis of the ICP-signal provides further
      options of an online monitoring of intracranial reserve capacity and the state of
      autoregulation. However, until now, there are no software solutions commercially
      available which would allow for such advanced signal analysis--the reason might
      be that the potential of advanced signal analysis has only been discovered within
      the recent years.

PMID- 12219643
TI  - [Clinical trial with the distal femoral nail].
AB  - METHODS: The clinical results after DFN-osteosynthesis of n = 56 AO
      classification 33A-fractures (32%), 33C-fractures (43%), 32X-fractures (21%) and
      treatment of non-union (4%) are presented. RESULTS: Follow-up was available for
      54 fractures (96%) after a mean of 1.2 years (range 0.2-2.8 years). 95% of
      patients showed full-weight-bearing with a knee flexion of 120 (60-140) degrees.
      Extension-deficit > 10 degrees was observed in 5.4%. All fractures were
      consolidated. One soft-tissue infection, one partial loss of reduction and one
      implant failure were observed. A significant axial malalignment was found
      radiologically in 17%, a loosened spiralblade or locking screw in 7.4%. In 91% of
      cases the result was judged as good to excellent by patients. CONCLUSION: The
      mechanical stability of the implant allows a save osteosynthesis of unstable
      supracondylar and complete articular femoral fractures without additional bone
      grafting. Mechanical stability and minimal invasive operative technique permit a
      safe bone healing without major complications.

PMID- 12219644
TI  - [Treatment of rare talus dislocation fractures. An analysis of 23 injuries].
AB  - METHODS: Between 1980 and 1996 we treated 23 patients for dislocated fractures of
      the talus. The injury was caused by a car accident in 61% and a high fall in 22%.
      Five patients had open wounds (22%), two developed compartment syndrome of the
      foot (9%) at an early stage, and 11 patients had multiple injuries. We used the
      classifications of Hawkins and Marti/Weber. All fractures were surgically treated
      by fixation with screw osteosynthesis, percutaneous wire transfixation, and/or
      external fixation. Fifteen patients with dislocated fractures of the talus
      underwent clinical and radiological follow-up examinations using the Kiel score.
      RESULTS: Four patients had excellent and three good results. In five patients
      with moderate, two with adequate, and one with poor results, we found additional
      injuries to the ipsilateral foot or leg in 50%. Of those patients, 73% developed
      peritalar arthrosis and 39% talar necrosis. Due to bony defects, anatomical
      reconstruction was unsatisfactory in 48%. CONCLUSIONS: Even immediate anatomical
      reduction and sufficient stabilization cannot always decrease the rate of talar
      necrosis and peritalar arthrosis.

PMID- 12219645
TI  - [Lateral clavicular fractures in children and adolescents].
AB  - From 1996 to 1999, 572 fractures of the clavicle were treated in our department,
      26 of which were located at the lateral end of the clavicle. Two children were
      operated: in one a closed reduction of the fracture under general anesthesia was
      performed, and in the other the fracture required open reduction with internal
      fixation. All other fractures were treated conservatively with a figure-of-eight
      clavicle strap for 3 weeks. A follow-up study was performed in autumn 2000.
      Sixteen patients came to our outpatient department for clinical and radiological
      control, and three patients informed us by phone. All patients including the two
      treated under general anesthesia were fully recovered and had no problems doing
      their job and engaging in different sports. The radiological controls showed a
      good ossification without visible deformity of the clavicle.

PMID- 12219646
TI  - [The burned hand. A computer-assisted study of late function of 67 burned and
      operated hands].
AB  - A good functional outcome of the hand is important in the rehabilitation of
      severely burned patients. The aim of the study was to evaluate the late
      functional outcome of deeply burned hands using a computer aided system and to
      correlate the function with the distribution of the hand burns. Over a 12-year
      period 378 patients whose acutely burned hands had been operated on at the burn
      center of the university hospital Aachen were invited to a follow-up examination.
      67 burned and operated hands were evaluated 57 (3-364) months after the burn by
      the computerized evaluation system EVAL. Active flexion and extension, grip
      strength, pinch (key, 3-tip and 2-tip), moving 2-point sensitivity and the
      pattern of skin grafts and scars were assessed. The use of the hand in daily
      activities was evaluated by a questionnaire. The hands were classified in 4
      groups according to the burn pattern: I: patchy burns (total < 12 cm2), II:
      confluent dorsal burns, III: confluent palmar burns, IV: mutilating burns. Good
      results were found in group I (n = 25), comparable to normal hand function. In
      group II (n = 25) there was a significant loss of total active flexion with
      preserved strength. Increased extension lag and impaired grip strength
      characterized group III (n = 8). Late functional results in group IV (n = 9)
      depended on the reconstructive procedure. Between the 4 groups there were
      significant differences in function. The results were well correlated to the burn
      pattern and its extent according the classification.

PMID- 12219647
TI  - [Retrograde intramedullary nailing of knee para-articular fractures in paraplegic
      patients].
AB  - INTRODUCTION: Patients with spinal cord lesions suffer injury even by marginal
      trauma, especially in the area of the knee joint. Because of lost sensitivity and
      proprioception, the treatment of the fracture has to be minimally invasive but
      stable enough for physiotherapy. METHODS: There were 18 patients with 20
      fractures near the knee: 15 fractures of the supracondylar femur were treated
      with a retrograde intramedullary GSH nail and 5 fractures of the proximal tibia
      with a new retrograde nailing technique. RESULTS: At review all patients had a
      good motion range of the knee joint (> 100 degrees), and ankle joint motion was
      free. CONCLUSION: We saw in this study that the GSH nail is an excellent method
      for stabilizing supracondylar fractures of the femur in paraplegic patients
      because the treatment is minimally invasive and the fracture is stable enough for
      physiotherapy. The retrograde nailing of proximal fractures of the tibia is a
      good alternative method for treatment of patients with spinal cord lesions.

PMID- 12219648
TI  - [Prosthesis implantation in the proximal ankle joint--a real therapeutic
      alternative in post-traumatic arthrosis?].
AB  - The results of total ankle arthroplasty were poor in the 1970s and 1980s compared
      to those of the arthrodeses. Because of the good long term results this technique
      has been accepted as the treatment of the choice for posttraumatic arthritis of
      the ankle. Recently the development of an unconstrained total ankle arthroplasty
      with an additional mobile polyethylene inlay between the fixed tibial and the
      talar component which enables a three dimensional range of motion seems to
      improve significantly the long term results of total ankle replacement. This
      technique, however, is an extremely demanding procedure. The range of motion
      after total ankle replacement following posttraumatic arthritis is poor compared
      to the results of total ankle replacement for rheumatoid arthritis. Furthermore,
      these data are obtained yet only by a few experienced surgeons in specialized
      centers. Further clinical trials have to be performed to answer the question
      whether the total ankle arthroplasty is a reliable alternative treatment of
      posttraumatic arthritis of the ankle. At present, the arthrodesis should be
      regarded as the treatment of choice for the posttraumatic arthritis of the ankle
      joint.

PMID- 12219649
TI  - [Assessment of the validity of the Ottawa Knee Rules for standard roentgen images
      of acute knee injuries].

PMID- 12219650
TI  - [Forearm shaft fracture of the adult].

PMID- 12219651
TI  - [New concept in therapy of distal tibial metaphyseal fractures and pilon
      fractures with minor dislocations and severe soft tissue damage].
AB  - The treatment of pilon fractures and distal metaphysial tibia fractures demands
      very high standards on the osteosynthesis material regarding the soft tissue and
      the essential joint reconstruction. The selection of the surgical entrance,
      particularly in case of a critical arterial or venous circulation and the
      possible irritation of the soft tissue caused by the osteosynthesis material led
      us to search for alternative osteosynthesis methods. After the elaboration of a
      pre-clinical study and good first results in the treatment of patella, olecranon
      and ankle joint fractures by means of the XS-nail the latter is now also employed
      for pilon fractures. Within a time period of 8 month 5 fibula fractures coming
      with pilon fractures had been treated with the XS-nail. This case report will
      demonstrate both the technique of treatment and the flexibility of the new
      implant.

PMID- 12219652
TI  - [Extracorporeal lung support and endovascular stent in traumatic aortic rupture
      and severe lung failure].
AB  - Blunt thoracic injury in association with aortic rupture represents a life
      threatening situation. Surgical repair used to be the preferred method of
      treatment. Because most patients are multiple trauma patients including head
      injuries, bone fractures and respiratory failure, urgent surgical procedures
      portend excessively high morbidity and mortality rates. Delay in operative
      management bears the risk of exsanguinating hemorrhage, secondary complications,
      prolonged hospital stay with increased costs. We present here an alternative
      treatment protocol including pumpless extracorporal lung assist and endovascular
      aortic stent graft placement in a 20-year old traffic accident victim. This
      procedure may be an especially useful treatment option in managing patients with
      complex lung and aortic pathology primarily not suitable for transportation or
      surgery.

PMID- 12219653
TI  - [Primary subcutaneous hematogenous osteomyelitis in childhood].
AB  - The most frequent form of bone infection is haematogenous osteomyelitis (HOM),
      typically affecting infants and children. Dependent on the virulence of the
      pathogen and the patients immune response, one can distinguish between the acute
      (AHOM) and primary subacute haematogenous osteomyelitis (PSHO). In contrast to
      AHOM, diagnosis of PSHO is severely impeded in that clinical and blood-chemistry
      findings usually do not enable differentiation from primary malignant bone
      tumors. With a comparable age predilection and clinical symptoms, as well as very
      similar conventional radiographic, MRI- and bone-scan-findings, the most
      important differential diagnosis is Ewing's-sarcoma. The here demonstrated case
      of a 12 year-old girl shows that PSHA may imitate a sarcoma very closely, even
      concerning such usually fairly reliable radiographic aspects like osteolysis and
      lamellar periostal bone reaction. Despite the use of MRI, the diagnosis initially
      remained uncertain and a malignant bony lesion could only be ruled out after open
      biopsy and histopathological evaluation.

PMID- 12219654
TI  - [Femoral shaft fracture and secondary diagnosis of ipsilateral femoral neck
      fracture. Typical constellation or a complication of the distal femoral nail
      (DFN)?].
AB  - We present a case of two patients with a distal femur shaft fracture due to a
      high velocity trauma. Both were treated with a distal femur nail (DFN). After
      mobilisation a fracture of the neck of the femur was diagnosed which was not seen
      in the x-rays on admission. In this paper we discuss whether this is a typical
      constellation of ipsilateral fractures of the neck of the femur in femur shaft
      fractures or a complication of implantation of a DFN. Immediately after operative
      treatment of a femur shaft fracture specifically after high velocity trauma or in
      polytraumatized patients an x-ray of the hip in two plains should be made in the
      same narcosis. A possible fracture of the neck of the femur could be treated at
      same time. Post-operatively a further diagnostic should be done in case of
      suspicion, e.g. pain during mobilisation.

PMID- 12219655
TI  - [Ipsilateral knee and hip joint dislocation].
AB  - Knee and hip dislocations are often serious injuries with an uncertain outcome.
      Simultaneous ipsilateral dislocation of the knee and hip joints is very rare;
      consequently, there is an inadequate amount of literature on the subject. In this
      case report we present a 35-year-old male patient with this combination of both
      injuries and discuss it in comparison with the available literature. This case
      report shows, that a methodical and sequential treatment can lead to good results
      in spite of this complex combination of injuries.

PMID- 12219656
TI  - [Applications of extracorporeal shockwave therapy in orthopedics. Where do we
      stand 10 years later?].

PMID- 12219657
TI  - [Physical-technical principles of extracorporeal shockwave therapy (ESWT)].
AB  - Extracorporeal shock waves in orthopaedics are currently applied in the treatment
      of chronic enthesiopathies such as lateral epicondylitis, plantar heel spur, as
      well as in calcifying tendinitis of the shoulder or in bony nonunions. Detailed
      knowledge of physical parameters and properties of shock waves appear to be
      necessary to determine clinically relevant dose-effect relations and to make
      shock wave devices, clinical results, and basic science in shock wave therapy
      more comparable. This study gives an overview of physical parameters and
      properties in shock wave therapy. Measurement technologies, types of shock wave
      devices, and mechanisms of shock waves are also described.

PMID- 12219658
TI  - [Tissue-induced changes of the extracorporeal shockwave].
AB  - Extracorporeal shock wave therapy has been applied very frequently for more than
      2 decades. Excellent results in clinical application and research led to
      widespread use of this noninvasive procedure. Until now the actual mode of action
      and biochemical pathways after extracorporeal shock wave therapy (ESWT) remain
      unknown. A small number of technical parameters could be determined after
      improved technical methods and sensor devices had been designed. It is also still
      unclear how these technical findings apply to the clinical setting. Therefore, we
      investigated the influence of musculocutaneous tissue on shock wave focus. A
      tissue thickness of 15 mm significantly influenced focus characteristics. We
      found distinct spreading and slight lateral deviation of the focus. In the same
      way, the peak positive pressure was significantly reduced after the shock waves
      had passed the musculocutaneous model. The study demonstrates that in vitro
      results could not be transferred directly to clinical or in vivo conditions. The
      clinical application of extracorporeal shock waves should be modified in
      intensity and number of shock waves depending on individual anatomic conditions,
      indication, and location.

PMID- 12219659
TI  - [Extracorporeal shockwave therapy (ESWT) in epicondylitis humeri radialis. A
      review of the literature].
AB  - This review article evaluates therapeutic procedures and clinical findings of
      extracorporeal shock wave therapy (ESWT) when used for lateral epicondylitis (LE)
      based on systematic research of the literature. A total of 20 studies were
      identified, 2 of which had been carried out as prospective, randomized, and
      controlled studies; the biometric quality of the remaining is clearly inferior.
      The inclusion and exclusion criteria used in the studies tallied well. In the
      more recent literature, important ESWT parameters such as energy used, number of
      impulses and treatment sessions, and locating methods also tallied in part. The
      studies reported only occasional side effects that could be evaluated as
      harmless. When evaluating the clinical success of ESWT, it was stated that about
      40-80% of the patients achieved a good or very good result at follow-up
      examinations after 3-12 months. However, in the single placebo-controlled and
      blinded study with an independent observer, the same therapy results were
      achieved in the control group where a local anesthetic was used as in the ESWT
      group. For this reason, it has been concluded that up to now no clinically
      relevant efficacy has been proven for the use of ESWT for LE. It should no longer
      be applied clinically as a matter of course, but only as part of high-quality
      studies with an adequate control group and blinding of patients and follow-up
      examiners. Due to the pain incurred when applying ESWT and the risk of uncovering
      the masking, the blinding of the patients must be checked in each further
      controlled ESWT study.

PMID- 12219660
TI  - [Extracorporeal shockwave therapy (ESWT) in epicondylitis humeri radialis. Short
      term and intermediate-term results].
AB  - Eighty-five patients with a chronic therapy-resistant lateral epicondylitis (LE)
      were treated with extracorporeal shock wave therapy (ESWT). All patients had been
      previously treated with physical therapy, local injections, and other
      conservative procedures for at least 6 months. Three weekly sessions of ESWT were
      performed under local anesthesia with a Dornier Epos Ultra (energy flux density
      0.05-0.18 mJ/mm2). Complications such as small hematomas were only found in four
      patients. After a mean follow-up of 30.7 months, 78 patients could be evaluated
      with the Roles and Maudsley score. Of these 30.8% had an excellent and 42.3% a
      good result, while 11.5% had a fair and 15.4% a distinctly poor outcome. Pain
      perception under stress conditions was assessed by the visual analog scale, which
      decreased significantly from 6.5 before ESWT to 2.0 after ESWT (p < 0.0001). A
      graduated local pressure pain on lateral epicondyle remained in 71.8% of the
      patients as a residual symptom. Sixty-two patients declared their satisfaction
      with the ESWT and would agree to have the therapy repeated.

PMID- 12219661
TI  - [Extracorporeal shockwave therapy in symptomatic heel spurs. An overview].
AB  - Extracorporeal shock wave application (ESWA) has been successfully used for years
      in routine clinical management of plantar fasciitis. So far no clinical trails
      have shown the efficiency in placebo-controlled protocols. This paper presents an
      overview of conservative and operative treatment modalities with respect to their
      efficacy. Results of a prospective randomized placebo-controlled double-blind
      multicenter trial to show efficiency and safety of ESWT are presented. In
      patients treated conservatively without success, a single shock wave application
      can improve the condition significantly compared with placebo treatment (p =
      0.0149). The Roles and Maudsley score also showed a significant improvement
      between the groups, with 61.6% good or excellent results in the verum group and
      39.7% in the placebo group (p = 0.0128). Therapy-related side effects (local
      swelling, petechia) are rare. The data presented in this study led to FDA
      approval in January 2002 of the shock wave device used.

PMID- 12219662
TI  - [Extracorporeal shockwave therapy (ESWT) in tendinosis calcarea of the rotator
      cuff. Long-term results and efficacy].
AB  - Calcifying tendinitis (TC) of the rotator cuff is a transient shoulder disease
      with a high rate of spontaneous resorption of the deposit. Therefore, primary
      treatment should be conservative. In cases of persistent pain despite
      conservative treatment, extracorporeal shock wave therapy (ESWT) can be performed
      as an alternative minimally invasive method. Various short-term studies have
      demonstrated the efficiency of ESWT for TC. To evaluate the short- and long-term
      results, complications, and the number of operations avoided by ESWT, a
      prospective study with 115 patients was performed over a period of 4 years. The
      patients had received high-energy ESWT once (group A: n = 56) or twice (group B:
      n = 59). Six months after therapy, 47% in group A and 77% in group B showed
      evidence of disappearance or disintegration of the calcium deposits. Pain relief
      was achieved in 45% of group A and 53% of group B. Four years after treatment,
      20% of the patients had undergone surgery on the involved shoulder. Of the
      remaining patients, 59% (68 patients) were seen for follow-up. Subjectively, 78%
      of group A and 87% of group B judged the treatment to be successful. X-ray
      examination revealed complete or partial resorption of the calcium deposit in 93%
      in both groups. The Constant score increased from 45 before treatment to 88 in
      group A and 85 in group B after treatment. ESWT was successful for about 70% of
      the treated patients with no long-term complications seen.

PMID- 12219663
TI  - [Extracorporeal shockwave therapy (ESWT) as therapeutic option in supraspinatus
      tendon syndrome? One year results of a placebo controlled study].
AB  - Extracorporeal shock wave therapy (ESWT) is seen as a therapeutic option in the
      treatment of chronic supraspinatus tendinitis by some authors. To test whether
      ESWT comprising 3 x 2000 pulses with the positive energy flux density ED+ of 0.33
      mJ/mm2 is clinically superior to a sham ESWT treatment, a prospective,
      randomized, single-blinded, placebo-controlled study with an independent observer
      was performed. Forty patients were treated either by verum ESWT or sham ESWT
      under local anesthesia. Target criteria were the age-corrected Constant score,
      pain at rest and during activity on a visual analogue scale, and subjective
      improvement. Patients who reported no subjective improvement after 12 weeks were
      deblinded and received verum ESWT if they had belonged to the placebo group
      (partial crossover). The results of the verum group lie within the range of
      results for ESWT published by other authors. Patients in the placebo group with
      local anesthetic showed equally good results. At 12 weeks, and 1 year after
      intervention, no difference could be found between the verum and placebo groups
      regarding Constant score, pain, shoulder function, or subjective improvement. The
      nonresponders to the placebo ESWT continued to show no improvement after
      receiving verum ESWT. This contradicts a specific ESWT effect. Based on the
      results of this placebo-controlled study, ESWT appears to have no clinically
      relevant effect on supraspinatus tendinitis. The study underlines the importance
      of a control group in evaluating new treatment methods for diseases with unknown
      natural history.

PMID- 12219664
TI  - [High energy extracorporeal shockwave therapy (ESWT) in pseudarthrosis].
AB  - The gold standard for treatment of pseudarthrosis is operation with
      osteosynthesis and grafting. More than 10 years ago, extracorporeal shock wave
      therapy (ESWT) was additionally introduced as a noninvasive and low-risk
      treatment for pseudarthrosis. The aim of our prospective study was to analyze the
      treatment effect in a homogeneous group of patients and to develop prognostic
      factors. Forty-three consecutive patients were included in this study. All
      patients had been operated on for trauma or undergone selective osteotomy and had
      developed pseudarthrosis that persisted for 9 months. All patients received high
      energy ESWT (0.6 mJ/mm2) with 3000 impulses (Siemens Osteostar) in one session
      under regional anesthesia. To differentiate active from inactive pseudarthrosis,
      a bone scintigraphy was compulsory. Clinical and radiological follow-ups were
      done at 4-week intervals starting 8 weeks after ESWT for 9 months. Cortical
      bridging was found in 31 of 43 (72.1%) pseudarthroses at 4.0 +/- 0.6 months after
      ESWT. Of 31 (80.6%) successfully treated patients, 25 had a positive scintigraphy
      compared to 4 of 12 (33.3%) treatment failures. Of 35 (82.9%) patients with a
      positive bone scintigraphy, 29 had bony healing compared to 2 of 8 (25%) patients
      with a negative bone scintigraphy. Six of these eight patients smoked more than
      20 cigarettes a day. ESWT is still a clinically experimental treatment method.
      The absence of complications justifies its use for pseudarthrosis treatment.
      Further controlled studies are mandatory.

PMID- 12219666
TI  - [Basic research of applying extracorporeal shockwaves on the musculoskeletal
      system. An assessment of current status].
AB  - Detailed knowledge concerning the action of extracorporeal shock waves on the
      locomotor system as well as concerning possible side effects of extracorporeal
      shock wave therapy (ESWT) are crucial to optimize the clinical use of ESWT for
      the treatment of illnesses such as calcific tendinitis of the shoulder, tennis
      elbow, plantar fasciitis, aseptic pseudarthrosis, and aseptic hip necrosis. This
      study presents the current knowledge gained from animal experiments, which have
      yielded important findings, in particular concerning possible side effects of
      ESWT. Very recent studies have also provided valuable insights into the molecular
      actions of extracorporeal shock waves on the locomotor system. Further
      intensified experimental animal research will greatly improve the scientific
      basis for the clinical use of ESWT in the near future.

PMID- 12219665
TI  - [3D-navigated high energy shockwave therapy and axis correction after failed
      distraction treatment of congenital tibial pseudarthrosis].
AB  - The treatment of congenital tibial pseudarthrosis using a distraction procedure
      as described by Ilizarov is a standard surgical intervention. Nevertheless, there
      are problems in achieving bony stability in about 10% of cases even after
      repeated surgery as reported by Lammens et al. (2000). Traub et al. (1999) found
      a rate of 50% amputations in 33 cases treated since 1927. To prevent an Ilizarov
      procedure from resulting in a delayed union or nonunion, Paley et al. (1992)
      recommended autografting immediately after distraction. Based on the good results
      in the stimulation of osteogenesis in adults, we started to treat delayed bone
      union following distraction treatment with high-energy shock wave therapy also in
      children. In patients suffering from congenital tibial pseudarthrosis with a
      deviation of the bony axis, we combine this surgery-substituting therapy with
      fixation of a Taylor spatial frame in order to correct the axis. Using this new
      method of treatment, we were able to achieve stability in four children who
      previously had had nonunion even after multiple surgical interventions.

PMID- 12219667
TI  - [2001 Annual Report of the Association of Orthopedic Rheumatology e.V].

PMID- 12219668
TI  - [Osteoporosis].

PMID- 12219669
TI  - [Universal neonatal hearing screening in Germany. What is the next step?].

PMID- 12219670
TI  - [Indications and diagnostic sensitivity of CT and MRI in the otorhinolaryngology
      field].
AB  - Of all malignant tumors, 4-5% affect the head and neck region. Computed
      tomography (CT) and magnetic resonance imaging (MRI) provide the means for us to
      determine the precise extent and depth of infiltration of space-occupying
      lesions, detect submucosal growth, stage lymph nodes preoperatively, and thus
      facilitate better preoperative planning. Thinner collimations of sections and
      shorter examination times are possible with modern multilayer spiral CT. Two
      dimensional and three-dimensional images can be calculated from the volume
      specifications to assess the skull base (coronal and sagittal sections) and the
      midline crossover of tumors as well as staging of lymph nodes (coronal section).
      Examination of laryngeal and hypopharyngeal function as well as determination of
      tumor perfusion are also possible. Detection of tumors that do not absorb any
      contrast medium (approximately 15%) is more difficult with CT. In addition to
      providing a high degree of tissue contrast, MRI makes it possible to directly
      acquire images in any number of planes. In contrast to CT, metallic artefacts
      hardly come into play. Infiltration of the dura and the cerebrum can be depicted
      better with MRI than with CT. The long examination time with MRI carries the risk
      of movement artefacts. In the head and neck region, it is important to suppress
      fat in T2-weighted sequences and in T1-weighted sequences after administration of
      contrast media. Inflammations in the head and neck region are only exceptionally
      clarified with CT or MRI. It is imperative that CT be performed before functional
      endoscopic operations of the paranasal sinuses. Further indications for CT and
      MRI in cases of inflammation are the diagnosis of retrotonsillar and
      parapharyngeal abscesses and ensuing complications as well as the diagnosis of
      osteomyelitis. Since conventional sialography is contraindicated in acute
      inflammation in sialolithiasis, magnetic resonance sialography can be employed.

PMID- 12219671
TI  - [Sense of smell before and after functional esthetic rhinoplasty].
AB  - BACKGROUND: The aim of the present study was to determine possible changes in
      olfactory threshold after functional and esthetic nasal operations and to
      evaluate whether these changes were recognized by the patients. METHODS: The
      study included 41 patients before and after nasal surgery (septoplasty,
      septorhinoplasty). Nasal airway resistance, olfactory thresholds, and subjective
      symptom scores were evaluated and compared pre- and postoperatively. The mean
      follow-up was 5.4 months. Olfactory performance was assessed using the Sniffin'
      Sticks. RESULTS AND CONCLUSIONS: The postoperative values in the screening test
      for olfactory sensitivity were not significantly different from those before
      nasal surgery. Nasal ventilation was improved postoperatively in all patients,
      assessed by determination of nasal airway resistance and subjective symptom
      scores. Besides an increase in nasal ventilation, functional and esthetic nasal
      operations can lead to improvement of olfactory function. The rarely seen
      postoperative increase in olfactory threshold does not seem to be subjectively
      recognizable by the patients.

PMID- 12219672
TI  - [Perioperative mortality in otorhinolaryngology tumor surgery].
AB  - BACKGROUND: Perioperative mortality is an important factor for quality assurance
      in surgery. For ENT-surgery only sparse data has been published. PATIENTS AND
      METHODS: A retrospective analysis of 1054 interventions performed on 775
      consecutive patients treated surgically for benign and malignant tumors of the
      head and neck was conducted during a 3-year period in 1995-1998. RESULTS: Of
      these patients, 34.1% were female and 65.9% male. Age ranged from 4-88 years with
      a mean age of 54.8 years. 489 patients (63.1%) were treated for malignoma and 286
      for benign tumors (36.9%). 0.9% (n = 7) of our patients (n = 775) died during the
      first 30 days after surgery. That means 0.66% of all surgical interventions (n =
      1054) were followed by post-operative mortality. DISCUSSION: In
      otorhinolaryngological surgery, post-operative mortality seems to be acceptable
      and low compared to other medical disciplines. The challenge for surgery must be
      to reach and preserve low perioperative mortality rates in the future. Finding
      the individually correct indication for surgical treatment must be guaranteed in
      order to reach this aim.

PMID- 12219673
TI  - [Fantoni translaryngeal tracheotomy (TLT) with rigid endoscopic control].
AB  - RATIONALE: The incidence of translaryngeal tracheotomy (TLT)-associated peri- and
      postoperative complications should be assessed prospectively. METHODS: TLT was
      carried out in operation-theatre under rigid endoscopic control. Peri- and
      postoperative complications, decanulement and late sequelae were assessed in ENT
      patients. In patients of other wards only perioperative complications were
      evaluated. RESULTS: 41 patients (26 ENT-patients, 15 patients of other wards)
      were tracheotomised by TLT. Perioperatively, we observed 3 technical problems
      (accidental pulling through of the tracheostomy tube). In 2 of these cases TLT
      could be completed without problems, in 1 case TLT was converted to surgical
      tracheotomy. Postoperatively, we could find no complications in 26 ENT-patients.
      Decanulation took place after 7 days on average. We found no tracheocutaneous
      fistulas or tracheostenoses, scars were unobtrusive. CONCLUSIONS: TLT with rigid
      endoscopy is a simple percutaneous tracheotomy-technique with a low complication
      rate.

PMID- 12219674
TI  - [Chronic rhinosinusitis in hypogammaglobulinemia. A morphological study].
AB  - Primary hypogammaglobulinemia (Bruton's disease) is a rare X-linked infantile
      immunodeficiency syndrome due to a B-cell defect. The patients suffer from acute
      and recurrent bacterial infections with chronic rhinosinusitis and chronic lung
      disorders. Immunoglobulin replacement therapy and antibiotics do not suffice in
      some cases, making sinus surgery to advance the drainage necessary. A 25-year-old
      man with hypogammaglobulinemia was treated with functional endoscopic sinus
      surgery and mucotomy of the turbinates. Tissue samples of the inferior turbinates
      were taken for histological and electron-microscopic examination. Immuno-electron
      microscopic methods were carried out with antibodies against substance P and
      calcitonin gene-related peptide (CGRP). Morphological investigations to better
      understand pathophysiological changes in hypogammaglobulinemia are rare.
      Pathological changes in the glands and venous vessels could be demonstrated. A
      rich neural supply and participation of neuropeptides such as substance P and
      CGRP could play a role in the unspecific defense via neurogenetic inflammation in
      these cases.

PMID- 12219675
TI  - [Hearing screening with automatic evaluation of TEOAE and a new method of
      automatic evaluation of early auditory evoked potentials. Optimization and field
      trial].
AB  - BACKGROUND AND OBJECTIVE: To make a rational decision as to which screening test
      might be adequate as a universal newborn hearing screening, different methods
      have to be tested under "real-life" conditions. In addition, a good reference is
      required as "golden standard." PATIENTS/METHODS: In the study presented here, an
      ABR with a novel algorithm for threshold-estimation was optimized and compared to
      TEOAE (Echoscreen) and DPOAE (GSI 60) in a three-step protocol using a standard
      click-evoked ABR (Evoselect) as reference of sensitivity and specificity.
      RESULTS: 26 ears were found to be hearing-impaired. All of them were also
      detected by each of the screening method (sensitivity 100%). Specificity in the
      final "step 2" of the study was around 87.7/92.3% for Echoscreen, 82.4/84.4% for
      DPOAE and 82.4/89.1 for Evoflash (left/right, respectively). Differences were not
      at all significant (X2-test, p > > 0.05). In summary, results were somewhat
      inferior to those found by other authors, probably due to more difficult
      conditions in the "real-life" setting. CONCLUSIONS: A higher rate of false-alarm
      shows that a two-step screening is necessary. Therefore, increased resources for
      diagnostic procedures are required.

PMID- 12219676
TI  - [New methods in ultrasound diagnosis. Opportunities and benefits in
      otorhinolaryngology].

PMID- 12219677
TI  - [Post-traumatic diagnosis of unilateral deafness].

PMID- 12219678
TI  - [News in medical jurisprudence October 2001 to April 2002].

PMID- 12219679
TI  - [Benign paroxysmal positional vertigo. Rapid diagnosis, successful treatment].

PMID- 12219680
TI  - [Environmental medicine. Pollution of the environment by anthropogenic products].

PMID- 12219681
TI  - [Poisoning due to heavy metals and arsenic].

PMID- 12219682
TI  - [Noise-induced damage. Medical aspects of noise exposure].

PMID- 12219683
TI  - [Somatoform disorders without findings--modern syndromes].

PMID- 12219684
TI  - [Genetic techniques and food. Are genetically modified foods a health risk for
      us?].

PMID- 12219685
TI  - [Inhaled pollutants in environmental medicine. Particles, diesel motor emissions
      and passive smoking].

PMID- 12219686
TI  - [Persistent chlorinated organic compounds and their relevance to environmental
      medicine].

PMID- 12219687
TI  - [Tuberculosis].

PMID- 12219688
TI  - [Recurrent syncope in left bundle branch block with normal PQ time].

PMID- 12219689
TI  - [35-year-old patient with oligoarthritis, bacteremia and aortic insufficiency].

PMID- 12219691
TI  - [Impairment of automobile driving capacity by therapeutic drugs].

PMID- 12219690
TI  - [Are ketolides replacing macrolides in chronic bronchitis?].

PMID- 12219692
TI  - [Antiproliferative coated stents and intracoronary brachytherapy: common traits
      and differences].
AB  - Intracoronary brachytherapy is the first internationally recognized, evidence
      based coronary intervention for in-stent restenosis. But the present and future
      role of brachytherapy is questioned by the first results of clinical trials with
      antiproliferative coated stents. This overview compares the status quo of both
      methods, concluding first practical considerations.

PMID- 12219693
TI  - [Psychosocial screening in coronary heart disease: 5 decisive questions].
AB  - There is overwhelming convincing evidence linking psychosocial factors to outcome
      of patients with coronary heart disease. Thus, assessment of psychosocial
      variables should be an integrated part of risk stratification. To facilitate
      psychosocial assessment in clinical practice and to identify a subset of patients
      possibly benefitting from extended psychological measures, a new semistandardized
      interview instrument is presented, called LIPS ("Lubecker halbstandardisiertes
      Interview zum Psychosozialen Screening"). Beside the well-known and relevant
      domains social support, emotional stress/vital exhaustion, anxiety and
      depression, a score for the global psychosocial impairment can be documented.
      LIPS requires no specialized psychological training, its time requirement is five
      to ten minutes and it is easily integrated into routine physical and psychosocial
      assessment. The presentation includes the original instrument in addition to its
      validation on standardized self-administered questionnaires.

PMID- 12219694
TI  - Initial experience with the Endicor X-sizer thrombectomy device in patients with
      ST segment elevation myocardial infarction.
AB  - We investigated 16 patients with ST segment elevation myocardial infarction who
      had an occluded coronary artery (TIMI 0) at initial angiogram. Instead of balloon
      angioplasty and stenting, patients were subjected to thrombectomy (Endicor X
      sizer) and stenting. In 15/16 patients the occlusion could be crossed by the
      thrombectomy device resulting in TIMI flow 3 in all of them. Thereafter, stenting
      was performed. At final angiogram all 15 patients continued to show TIMI flow
      grade 3. Twelve-lead ECG was performed prior to and post-intervention. ST
      elevation was measured as the sum of eight leads for anterior infarction and of
      five leads for inferior infarction. In 13/15 patients, ECG analysis was possible
      (2 developed bundle branch block post-intervention). In all 13 patients, a > 50%
      ST decrease of the initial amount of ST elevation was observed reaching a > 70%
      reduction in 11 patients. Procedural complications were low (one coronary
      dissection after thrombectomy) and 30 days follow-up was uneventful. Thrombectomy
      using the Endicor X-Sizer device may become an attractive mechanical reperfusion
      strategy for patients with acute myocardial infarction.

PMID- 12219695
TI  - Tei-Index in coronary artery disease--validation in patients with overall cardiac
      and isolated diastolic dysfunction.
AB  - BACKGROUND: The index "isovolumic contraction time and isovolumic relaxation time
      divided by ejection time" ("Tei-Index") has been demonstrated to provide useful
      information about disease severity and prognosis in patients with dilated
      cardiomyopathy and cardiac amyloidosis. In patients with coronary artery disease
      (CAD), the diagnostic utility of this index is unclear. We attempted to validate
      the Tei-Index in CAD patients with overall cardiac or isolated diastolic
      dysfunction. METHODS AND RESULTS: Sixty subjects were included who underwent left
      heart catheterization for invasive measurement of left ventricular end-diastolic
      pressure (LVEDP): 20 symptomatic CAD patients with overall cardiac dysfunction
      (defined by a LV ejection fraction (EF) < 45% (mean 27 +/- 8%) and a LVEDP > or =
      16 mmHg, (mean 22 +/- 6 mmHg), NYHA class 2.7 +/- 0.4, OCD group), 29 symptomatic
      CAD patients with isolated diastolic dysfunction (defined by an EF > 45% (mean 55
      +/- 8%), a normal end-diastolic diameter index (mean 2.8 +/- 0.4 cm/m2) and a
      LVEDP > or = 16 mmHg (mean 22 +/- 6 mmHg), NYHA class 2.3 +/- 0.4, IDD group) and
      11 asymptomatic control subjects (EF 65 +/- 9%, LVEDP 11 +/- 4 mmHg, CON group).
      After conventional 2-D- and Doppler echocardiographic examination, the Tei-Index
      was obtained. The Tei-Index was easily and reproducibly measured in all study
      subjects. In the OCD group, isovolumic contraction time was prolonged and
      ejection time was shortened in comparison to the CON group, resulting in a
      significantly increased Tei-Index (0.71 +/- 0.28 vs 0.40 +/- 0.11, p < 0.01). In
      the IDD group, isovolumic relaxation time was prolonged and isovolumic
      contraction time was shortened in comparison to controls, resulting in a largely
      unchanged Tei-Index (0.45 +/- 0.14, p = ns). Receiver operating characteristic
      curve analysis for the Tei-Index yielded an area under the curve of 0.92 +/- 0.04
      for separating patients with vs without OCD. Using a Tei-Index > 0.49 as a cut
      off, OCD patients were identified with a sensitivity of 96% and a specificity of
      86%. CONCLUSION: The Tei-Index is a valid and readily derived indicator of global
      cardiac dysfunction in CAD patients with impaired systolic and diastolic LV
      performance. The use of this index seems to be limited in CAD patients with
      primary diastolic dysfunction.

PMID- 12219696
TI  - [Duplex ultrasound determination of shunt volume in iatrogenic arteriovenous
      fistulas after heart catheterization].
AB  - AIM: To determine the shunt volume of iatrogenic arteriovenous fistula (AVF)
      following arterial puncture of the groin and to evaluate its impact on natural
      history and clinical outcome. METHOD: Over a period of 12 months, 22 patients (p)
      with a newly acquired AVF were followed up. The arteriovenous shunt volume was
      determined by means of colored duplex- and doppler sonography immediately after
      diagnosis of AVF. RESULTS: Spontaneous closure of AVF was seen in 10 p (46%)
      during follow-up examination, whereas 12 p (54%) showed a persistence of their
      AVF. The median (I50) shunt volume of closed AVF was 310 (250-350) ml/min and 350
      (160-510) ml/min for persistent fistulae (p = ns). A shunt volume of > or = 400
      ml/min was determined as a significant (p < or = 0.05) cut-off point for
      prolonged persistence of AVF. CONCLUSION: Because spontaneous closure of AVF was
      46% in the course of the first year, conservative management with regular duplex
      control seems to be justified at least for this duration. Patients with a shunt
      volume of > or = 400 ml/min have an increased risk of prolonged AVF persistence
      and therefore should be included in long-term follow-up with special attention to
      development of hemodynamic relevance.

PMID- 12219697
TI  - [Expansion of the Multilink-Tristar stent after direct implantation and
      predilatation: comparison of clinical, angiography and intravascular ultrasound
      parameters].
AB  - Coronary stenting has become the primary therapeutic option for many coronary
      lesions. As opposed to conventional stenting the advantages of direct stenting
      are a reduction of procedural time, radiation exposure and costs. However, data
      about the incidence of in-stent restenosis are so far not available. It was the
      aim of this prospective study to compare the expansion of the Multilink stent
      after direct stenting and predilatation by quantitative coronary angiography
      (QCA) and intravascular ultrasound (IVUS). Between January 2000 and June 2001, 82
      patients were assigned to direct stenting (46 lesions) or predilatation (40
      lesions) in lesions of coronary arteries > 3 mm. The procedural success rate was
      92% in patients undergoing direct stenting. The baseline clinical characteristics
      were similar in both groups. The comparison of the angiographic data shows that
      direct stenting was performed in lesions with a lower degree of stenosis (71 +/-
      12% vs 79 +/- 11%, p = 0.01) and that significantly shorter stents were used
      (14.4 +/- 3.0 vs 17.8 +/- 4.1 mm, p = 0.0007). The mean stenosis length was not
      significantly different in either group (10.5 +/- 3.4 vs 11.7 +/- 4.3 mm, n.s.).
      The QCA data after stent implantation show no differences of either implantation
      technique. Stent expansion was assessed by IVUS estimation of the proximal,
      distal and minimal in stent area. The minimal in-stent area (9.53 +/- 3.23, mm2
      vs 8.65 +/- 1.96 mm2, n.s.) and the stent symmetry index (0.88 vs 0.88 n.s.) were
      not different in either patient group. These results indicate that in this subset
      of selected coronary lesions > 3 mm, elective stent implantation with and without
      predilatation effectively can achieve comparable stent expansion as assessed by
      QCA and IVUS. In comparison to conventional stent implantation stents, which were
      implanted without predilatation, were significantly shorter to cover the same
      lesion length.

PMID- 12219698
TI  - [Radiation exposure of health personnel and patients in the heart catheterization
      laboratory in during vascular brachytherapy].
AB  - Interventional radiological measures can lead to high radiation exposures for
      medical staff. In order to determine the radiation exposure to staff and
      patients, the resulting radiation exposures were directly measured for 52
      measures at an cardiac catheterization laboratory with a new dosimetry system DIS
      (Direct Ion Storage). Beside the measurement of body dose behind the lead apron,
      measurements of radiation doses were performed in front of the lead apron and at
      the wrist of the physician. These measurements were taken as an approximation of
      the radiation exposure of the non-shielded body parts. The patients dose was
      estimated by placing a dosemeter close to the head of the patient and from the
      dose-area product. The mean value of body dose from 52 measurements for the
      physician behind the lead apron was 1.9 microSv per procedure with a range of 0-9
      microSv. In front of the lead apron, a mean value of 53.9 microSv (3-233 microSv)
      per procedure was obtained. The mean value of partial body dose at the
      physician's wrist was determined to be 163.2 microSv (12-603 microSv) per
      procedure. It could be shown that measures combined with interventions lead to
      higher exposures compared with measures without interventions. For the medical
      technician, the mean value behind the lead apron was 3.9 microSv (0-58 microSv)
      per procedure. For the patient, a mean value of 800 microSv (119-8642 microSv)
      was measured close to the head. The mean dose to the skin of the patient at
      radiation entrance was determined to be 307 mGy (70-1190 mGy). From this data,
      the radiation dose per year for the physician performing 1000 measures, was
      determined to be 1.9 mSv/year. This is below the new dose limit of 20 mSv/year.
      Also the estimations for the dose to the eye lens and the hands of the physician
      show no conflicts with actual dose limits when obeying all radiation regulations.
      The results for vascular brachytherapy did not show significantly higher
      exposures, compared with conventional measures including interventions.

PMID- 12219699
TI  - [Noncompaction of the left ventricular myocardium. Case report and review of the
      literature].
AB  - Left ventricular non-compaction is an unclassified cardiomyopathy characterized
      by an excessively prominent trabecular meshwork due to an arrest in myocardial
      morphogenesis. We report on a 51-year-old female patient with abnormal myocardial
      trabeculations associated with a congenital mitral valve stenosis post
      commissurotomy at the age of 14. In the present case report, clinical
      manifestation of the disorder included impaired left ventricular systolic
      function and atrial fibrillation. Noncompaction was diagnosed by echocardiography
      and levocardiography. In addition, a review of the literature on this rare
      disorder is presented.

PMID- 12219700
TI  - [Extreme cardiomegaly].
AB  - We report the case of 65 year old male patient with extreme heart enlargement.
      The patient was admitted to the hospital due to acute bleeding from varicose
      veins of the cardia. The endoscopic treatment by means of hemostatic clips and
      fibrine was successful. However the patient died two weeks later without having
      any complaints. The heart of the patient weighed 1350 g. Multiple coronary
      bypasses were found. There was also a recent myocardial infarction. The adoptive
      pathophysiologic changes accompanying extreme cardiomegaly are discussed.
      Numerous cases have been recorded of unusually large hearts, which in a few
      instances have even exceeded the one reported here. The analysis of observations
      reported in the literature reveals that rheumatic myocarditis and syphilitic
      aortitis were responsible for the majority of cases with extreme cardiac
      hypertrophy. Valvular deformities were also frequent findings. The occurrence of
      extreme cardiac enlargement in an elderly patient associated with multiple
      coronary bypasses has been not described so far.

PMID- 12219701
TI  - [Dementia and living environments].

PMID- 12219702
TI  - [Implementing change--steps toward living environment-oriented support for
      gerontopsychiatric patients and their caregivers, DGGG Congress, September 2001,
      Kiel].
AB  - The change which is necessary in home and long-term institutional elderly care,
      first of all, concerns the attitudes, values and norms and the acquisition of key
      competencies in dealing with people who have a gerontopsychiatric disease.
      Elderly care and attention of people suffering from dementia therefore requires a
      principal change in thought. The feeling of well-being is the pre-conditioning
      and starting point of the caring action, not its result. People suffering from
      dementia need the feeling of trust and security in order to be able to accept
      measures which seem to be illogical for them. The adjustment is therefore
      required from outside by shaping an environment, which provides security and
      orientation, and by building on caring attention relating to the patients' past
      interests and history. Participants of the conference could gather information
      about such innovative approaches in professional elderly care for people
      suffering from dementia in various workshops, gallery walk and a poster session.
      All presentations showed an approach, which was oriented towards the living
      environment and in which questions about the quality and continuity of life were
      considered to be as important as the aspects of the necessary elderly care. It is
      not a lack of knowledge about a subject and value oriented care for elderly
      people suffering from gerontopsychiatric diseases, but rather a deficit in
      putting this knowledge into practice, as the examples clearly showed.
      Gerontopsychiatric competencies have to be broadly developed and implemented.

PMID- 12219703
TI  - [Contribution of professional nursing to the life style of patients with
      dementia].
AB  - The care of older people with dementia increasingly requires that the family be
      involved in that care. The goals of the care giver are to continue daily life
      rhythms, offer greatest normality, and support the quality of life. This article
      describes the most important approaches and strategies from the perspective of
      daily living.

PMID- 12219704
TI  - [Dementia, trauma and transcultural nursing--the complex need for nursing care in
      Jewish geriatric nursing in Germany].
AB  - Complex nursing requirements are typical for the care of the Jewish elderly in
      Germany. As an example, the old age home care-center of the Jewish community in
      Frankfurt am Main, Germany, is need to show typical needs and care-profiles.
      Survivors of the holocaust who have survived persecution either in Europe or
      emigration are living in the center. A few years ago, elderly people who
      immigrated from the former Soviet Union and arrived in Germany only at age, began
      living in the center. Because the inhabitants of the center come from 18
      different countries, the structure of the residents is multiethnic and therefore
      more atypical for Germany. The daycare for people suffering from dementia is
      offered in two languages, which is also a new experience for Germany. The
      multiethnical and plurilingual orientation of the care center convinced the
      German Ministry of Health to promote new care-concepts as a model, which are
      based on these mentioned structures. The author also presents some ideas in order
      to experience the feeling of being a foreigner, which can be need as a basis for
      the development of an institutional culture.

PMID- 12219705
TI  - [Managing patients with dementia--current status and formulating dementia policy
      desiderata and options ].
AB  - The demographic and epidemiological scenarios, concerning persons with dementia,
      are in tension between the legal general conditions of care, on the one hand, and
      the conceptual alignment, on the other hand; this tension is hardly resolved by
      the momentary activities in health and care policy. Even on the level of
      assessment, there are scarcely any instruments to picture the specific needs of
      patients with dementia. Concepts of supply for persons with dementia are widely
      still divided by the differentiation between stationary and outpatient.
      Intelligent mixtures and paradigmatic reorientation towards normalization or
      split responsibility have not yet enfolded their embossing effects in practice.
      The care of persons with dementia is in many respects still bound in pre
      technical constellations: this applies to the conceptual bias inside an
      institution or service of old people's care, to legal and economical general
      conditions and instruments of control and in many ways also to the technical
      discourse. The relevancy of attendance of people with dementia today and in the
      future justifies talking about "dementia policy". Options for dementia policy lay
      in a consequent adaptation of the theory of the New Welfare Mix, which was
      developed by the political sciences, including discussion about normalization in
      the area of help for disabled people and in the reformulation of competence
      between the means of fringe benefits and employees' benefits in joint
      responsibility.

PMID- 12219706
TI  - [Geriatric assessment in family practice--results of concerted action by 7
      European countries].
AB  - General practitioners are faced with the complex medical care of an increasing
      number of older people. Traditional demand led care is not able to provide
      optimal management for this age group, since it has been shown that many
      important health problems remain unknown or not optimally treated. Preventive
      geriatric assessment offers primary health care providers new opportunities to
      focus their management on the particular health problems of older people. A
      European concerted action involving seven countries formed to develop a "standard
      assessment for elderly people in primary care (STEP)". The aim was threefold: 1)
      to identify important and preventable health problems in old age, 2) to supply
      health care planners and providers with scientific evidence of the corresponding
      preventive procedures, and 3) to initiate a practical assessment framework for
      use in European primary care practices. Using a strict methodological protocol,
      33 health problems were identified that potentially improve health outcomes in
      preventive programs for older people. A summary of the evidence is given for each
      of the included health areas. Taking the best available evidence, patients'
      preferences, and practice conditions into account, a preventive assessment
      program was developed containing validated and accepted instruments. The approach
      is algorithmic with a simple problem identification level and a further
      diagnostic stage. All recommended procedures are harmonized for common European
      use. An evidence-based preventive assessment program is expected not only to
      prevent disease and minimize disability and handicap, but it also offers health
      care planners a European data set of older peoples' needs for optimized resource
      allocation.

PMID- 12219707
TI  - [Social inequality and health of the elderly--classical or alternative status
      indicators?].
AB  - This article is focussed on the following two questions: first, whether socio
      economic status (SES) differentials in health among the aged vary by the
      indicators of health and SES applied. Secondly it is investigated how SES
      differentials in health vary by age. The analyses are based on a telephone survey
      of 821 older people (> or = 60 years) living in a private household in Germany.
      In addition to the traditional indicators of SES (education, income and
      occupational status) two alternative indicators (assets and home ownership) are
      used in the study. Self-rated health, depression (CES-D) and functional status
      according to Advanced Activities of Daily Living are introduced as health
      indicators. Results of multiple regression analyses show that associations
      between income and the health indicators were comparably strongest. Education,
      occupational prestige, assets and home ownership were not consistently related to
      health, especially after controlling for the remainder of the SES indicators.
      Thus, home ownership and assets do not predict health significantly beyond the
      effect of the traditional indicators of SES. With regard to age-related
      variations of the social gradient results were not consistent: In terms of self
      rated health associations do not differ between the age groups (60-65, 66-74,
      75+), while associations between traditional SES indicators and depression tend
      to become stronger among those aged 75 years and older. With regard to functional
      status there were no significant associations with socio-economic status in the
      multivariate model among those aged 75 years and older. The present study shows
      that the magnitude of the association between social inequality and health among
      the aged as well as age related changes in the social gradient depend on the
      indicators of SES and health applied. Because the analyses are based on cross
      sectional data it is not possible to identify causal relationships or to separate
      age effects from cohort effects. Therefore longitudinal studies are needed in
      which traditional as well as alternative indicators of SES are used that are
      appropriate for older adults in general and important for an explanation of
      differentials in health among the aged in particular.

PMID- 12219708
TI  - [Estimating length of stay of geriatric rehabilitation patients].
AB  - The aim of the study was to identify the most influential predictors of length of
      stay (LOS) among data, which are usually available on admission in geriatric
      rehabilitation units, such as diagnosis, functional limitations, age, gender, or
      marital status. Datasets of 6740 consecutive patients of a geriatric
      rehabilitation clinic have been retained for the analysis. As the density
      distribution of the LOS was grouped in intervals of 0-4, 4-6, 6-8 and 8 weeks and
      more, separate multivariate logistic regression models have been tested for the
      four intervals of LOS as well as for each of the four intervals separately. Some
      functional limitations on admission are significantly associated with longer LOS:
      limitations in dressing are associated with LOS of 6-8 weeks (OR = 1.47; CI =
      1.32-1.65), and limitations in using the toilet are associated with LOS of 8
      weeks and more (OR = 3.50; CI = 2.98-4.10). Shorter LOS of 0 to 4 weeks are
      significantly predicted by being respectively married (OR = 1.52; CI = 1.37
      1.68), 75 years old and alder (OR = 1.29; CI = 1.16-1.43) or having a femur
      fracture (OR = 1.45; CI = 1.22-1.73). Single ADL-limitations such as in using the
      toilet or in dressing have a high predictivity of the LOS. Married patients and
      older patients are discharged earlier. Social characteristics like those
      subsumated under age or marital status seem to play a more important role as
      expected in determining the LOS in geriatric rehabilitation patients.

PMID- 12219709
TI  - [Knowledge concerning illness, expectations and perceptions of treatment of
      elderly stroke patients and family caregivers--a prospective study during
      inpatient treatment].
AB  - Forty-five stroke patients and their 45 proxies were interviewed after the
      patients' hospital admission and before discharge. The topics of the interviews
      were disease knowledge, expectations in and judgement about therapy, estimation
      of functional health status (CCOP/WONCA Charts), and prognosis. The patients and
      proxies were also asked to name the patient's actual three most important health
      problems. The depressive symptomatology in the patients (geriatric depression
      scale) and their ADL status (Barthel Index) were evaluated on admission and
      before hospital discharge. The proxies' general knowledge of disease was superior
      compared to that of the patients. There were knowledge deficits regarding
      individual risk factors and secondary prevention, in particular. Information was
      predominantly obtained from physicians. However, an additional need for
      information on prognosis and prevention, in particular, was expressed by patients
      and proxies before hospital discharge. There was a high agreement between the
      patients and their proxies in mentioning the patients' actual three most
      important health problems, apart from psychological problems. These were
      mentioned only by the proxies but not by the patients themselves. Depressive
      symptomatology in the patients increased significantly. There were associations
      of depression with the level of the Barthel Index score and the patients' self
      estimation of functional health status before and after the stroke. Full recovery
      was expected by one half of the patients, on admission. The patients' primary
      therapeutic goal was the ability to walk again. Their ADL status improved
      significantly, as measured by a mean increase in the Barthel Index score by 22
      points. The patients and their proxies, as well, judged the result of treatment
      equally high. The proxies' total satisfaction with patient care was significantly
      related to their ratings of separate parts of patient care regarding nurses,
      therapists, and physicians, to their expectations in therapy, and the
      satisfaction of their own personal needs. The results of the study revealed a
      particular need for information on prognosis and secondary prevention of stroke.
      Furthermore, depression and coping with consequences of the disease should be
      important issues in counselling of stroke patients and their proxies. The results
      regarding patient and proxy satisfaction with care were of importance for
      internal discussion in the clinic.

PMID- 12219710
TI  - [Position regarding the "Hamburg Declaration"].

PMID- 12219711
TI  - House passes Medicare bill with payment relief.

PMID- 12219712
TI  - President signs nursing parity bill.

PMID- 12219713
TI  - HHS, CMS reject transfer payment expansion.

PMID- 12219714
TI  - Senate postpones provider package, approves generic Rx bill.

PMID- 12219715
TI  - Medical liability update.

PMID- 12219716
TI  - Improving the quality of care.

PMID- 12219717
TI  - Nurse Reinvestment Act is a solid step forward.

PMID- 12219718
TI  - Monitoring techniques for diabetes mellitus in the dog and the cat.
AB  - One of the keys to achieving glycemic control in animals with diabetes mellitus
      is the appropriate selection and interpretation of analytic monitoring tests.
      Diabetic animals are subject to many of the same problems described in human
      diabetics. Diabetics are more susceptible to infection, and wound healing is
      often impaired. Decreased insulin promotes lipolysis and moderate hyperlipidemia,
      which can lead to falsely lowered fructosamine levels, impaired renal
      circulation, and atherosclerosis. Hyperglycemic, hypoinsulinemic animals continue
      to lose weight despite an increased appetite and an increased intake because they
      are not able to use glucose. Many unregulated diabetic animals will present with
      vomiting and diarrhea that can exacerbate electrolyte abnormalities seen with the
      osmotic diuresis present in an uncontrolled state. Canine diabetics are prone to
      cataract formation secondary to sorbitol accumulation in the lens. Cats, on the
      other hand, can present with diabetic distal neuropathy, which may be reversible
      with appropriate treatment. With all of these potential complications, it is
      important to monitor these animals regularly; this is the only way that glycemic
      control can be properly maintained over time. This article reviews the monitoring
      parameters available to the modern practitioner and outlines the benefits of each
      test, as well as caveats, in their interpretation.

PMID- 12219719
TI  - Portable blood glucose meters as a means of monitoring blood glucose
      concentrations in dogs and cats with diabetes mellitus.
AB  - The use of portable blood glucose meters (PBGM) has become common in veterinary
      medicine as a rapid means of monitoring animals' blood glucose in a variety of
      medical conditions. These hand-held monitors allow for diagnostic and therapeutic
      decisions to be made quickly and relatively inexpensively using only a small
      amount of blood. Both in conditions resulting in hyperglycemia, such as diabetes
      mellitus, and in those resulting in hypoglycemia, such as sepsis or the presence
      of an insulinoma, veterinarians have come to rely on PBGM to provide critical
      information on the status of their animal patients. In particular, PBGM are
      frequently used to measure individual blood glucose values in an animal over a
      period to create a blood glucose curve when evaluating the effectiveness of
      insulin therapy in diabetic dogs and cats.

PMID- 12219720
TI  - Critical care monitoring considerations for the diabetic patient.
AB  - Diabetes mellitus (DM) is a common endocrine disease encountered in the emergency
      and critical care setting. The diabetic Ketoacidotic (DKA) animal represents an
      extreme of the DM patient with regard to hyperglycemia and acid-base and
      electrolyte derangements. Prompt diagnosis of DKA in a critical patient and rapid
      initiation of appropriate therapy are necessary for a positive outcome. The steps
      of treatment, in order of importance, include initiation of intravenous fluid
      therapy, insulin therapy, electrolyte replacement, and reversal of the metabolic
      acidosis. The main goals of therapy--including correction of dehydration,
      electrolyte abnormalities and acidosis via aggressive fluid therapy with
      electrolyte supplementation and correction of ketoacidosis and hyperglycemia via
      initiation of insulin therapy--can be achieved if these steps are followed.
      Because of the severity of metabolic alterations in the DKA animal, frequent and
      careful monitoring are paramount because they will allow the clinician to tailor
      treatment to each case.

PMID- 12219721
TI  - Troubleshooting the diabetic small animal patient.
AB  - Effective troubleshooting for a diabetic small animal patient starts with the
      initial diagnosis of diabetes. Preempting trouble with a thorough and complete
      history, physical examination, laboratory assessment, and extensive and
      thoughtful client education before discharge, are crucial first steps toward
      avoiding trouble altogether. As problems arise, careful consideration of the many
      variables that contribute to effective diabetic control is necessary. As
      monitoring strategies evolve and treatment options expand, the clinician's
      ability to accurately assess and adjust the glycemic control in his or her
      troubled diabetic patient improves. Common causes of trouble in diabetic patients
      are reviewed and various strategies for the diagnosis and management of these
      disorders are discussed in this article. Every effort was made to draw from
      recently published reports of clinical cases. Few diseases will tie together
      owner, patient, and therapy as intimately as diabetes mellitus, and few problems
      will be solved without fully considering all potential factors.

PMID- 12219722
TI  - Home monitoring of the diabetic pet.
AB  - Home monitoring of the diabetic pet is a challenging proposition for many pet
      owners. Diabetes, unlike many other diseases, requires that the client, not the
      veterinarian, treat the disease. It is crucial that veterinarians reinforce and
      educate clients that successful treatment of diabetes mellitus will depend solely
      on the client's actions throughout the course of the treatment. This article
      provides guidelines on educating clients in the home monitoring process. This
      commonsense approach covers elements of in-home monitoring, including general
      appearance, clinical signs, behavior changes, feeding schedules, and medication
      administration. Additionally, thorough explanation is provided for clients who
      wish to take a more active role in obtaining and monitoring blood and urine
      chemistry values. This information is provided to assist the veterinary
      technician and veterinarian in educating clients of their responsibility in
      treating this disease.

PMID- 12219723
TI  - A review of the applications of imiquimod: a novel immune response modifier.
AB  - Imiquimod (1-(2-methylpropyl)-1 H-imidazo[4,5-c]quinolin-4-amine) and its
      analogues are a class of non-nucleoside imidazoquinolinamines (hetero-cyclic
      amine) that activate the immune system through localised induction of cytokines,
      such as IFN-alpha, -beta, and a number of endogenous interleukins. The exact
      mechanism of its actions are still unexplored, although when tested in a number
      of cell culture systems, imiquimod demonstrated no inherent antiviral or
      antiproliferative activity in vitro, whereas, due to its reported ability to
      produce onsite stimulation and secretion of cytokines in various in vivo studies,
      such types of immune response modifiers have been shown to cause diverse
      biological functions, involving immunoregulatory, antiviral, antiproliferative
      and antitumour activities. These data support a rational justification to
      consider imiquimod as an innovative topical agent to treat various cutaneous
      diseases. Since its synthesis in 1980,several studies using animal models and
      human subjects have been reported substantiating its usefulness as a treatment
      option for various skin disorders such as genital warts, genital herpes,
      molluscum contagiosum, basal cell carcinoma and psoriasis. Imiquimod is insoluble
      in water but in most of the clinical studies its incorporation from 1 - 5% by
      weight in an oil-into-water cream emulsion has been reported as being well
      tolerated with mild-to-moderate drug-related side effects, such as itching,
      burning sensation, pain, erythema, erosion and oedema. As a potent immune
      response modifier and an agent stimulating cell-mediated immune responses,
      imiquimod appears to be a promising drug to treat many skin disorders, infections
      and neoplasms.

PMID- 12219724
TI  - Sex hormones and chronic headache in women.
AB  - Women experience changes in headache pattern in relation to changes in their
      reproductive cycles. Menarche, menses, pregnancy, menopause and the use of
      exogenous oestrogen-containing medications frequently alter baseline headache
      patterns. Changing patterns of headache in women may be linked to alterations in
      levels of sex hormones. Sex hormones directly influence headache by affecting the
      activity of a variety of neurochemicals important for headache, including
      serotonin (5HT). Treating headache alterations in women may include therapies
      that modify sex hormones or neurochemicals.

PMID- 12219725
TI  - Safe in his hands? Interview by Colin Parish.

PMID- 12219726
TI  - Ask and you might receive.

PMID- 12219727
TI  - Next steps. Interview by Dina Leifer.

PMID- 12219728
TI  - Information unlimited.

PMID- 12219729
TI  - Club class.

PMID- 12219730
TI  - Positive thinking.

PMID- 12219731
TI  - [Practice guidelines in gastroenterology. Use of anti-TNF agents in inflammatory
      bowel disease. European guide 2001-2003].

PMID- 12219732
TI  - [Report fron the Inaugural Congress of the World Society for Reconstructive
      Microsurgery in Chang Gung Memorial Hospital, Taipei, Taiwan].

PMID- 12219733
TI  - Magnesium precipitate hot start method for PCR.
AB  - For the amplification of HIV-1 gag gene, and other challenging targets, a simple
      new hot start PCR protocol is presented which consists simply and entirely of the
      buffer system. This novel buffer composition and reaction assembly protocol for
      PCR includes magnesium and phosphate combined at high concentration in addition
      to standard buffer reagents. The resulting magnesium-containing precipitate
      provides a hot start for PCR, since the magnesium in the precipitate is
      unavailable to DNA polymerase until thermal cycling. No extra manipulations at
      the thermal cycler or changes to standard thermal cycling profiles are necessary.
      Upon normal cycling, the magnesium becomes fully available within the first 3
      cycles. The method effectively prevents premature primer extension by several DNA
      polymerases or mixtures of DNA polymerases tested, including Klentaql, KlentaqLA,
      Pfu, and full-length wild-type DNA polymerase. Once the precipitate is formed,
      the hot start buffer is stable and functional for at least a week at -20 degrees,
      4 degrees , or 25 degrees. We demonstrate that the method is as effective as a
      manual hot start (addition of magnesium at or above primers'annealing
      temperatures) for several target gene amplifications which require a hot start.

PMID- 12219734
TI  - Standardised in vitro electrophysiologic measurements using isolated perfused
      porcine hearts--assessment of QT interval alterations.

PMID- 12219735
TI  - Bibliography. Current world literature. Disorders of pulmonary circulation.

PMID- 12219736
TI  - Bibliography. Current world literature. Sarcoidosis: the first quarter of the
      21st century--diagnosis and management.

PMID- 12219737
TI  - Small molecule analysis by MALDI mass spectrometry.
AB  - This review focuses on the application of matrix assisted laser
      desorption/ionization (MALDI) mass spectrometry to the characterization of
      molecules in the low mass range (<1500 Da). Despite its reputation to the
      contrary, MALDI is a powerful technique to provide both qualitative and
      quantitative determination of low molecular weight compounds. Several approaches
      to minimize interference via sample preparation and matrix selection are
      discussed, as well as coupling of MALDI to liquid and planar chromatographic
      techniques to extend its range of applicability.

PMID- 12219738
TI  - Evaluating the effects of a peer support programme on adolescents' knowledge,
      attitudes and use of alcohol and tobacco.
AB  - This study was designed to evaluate the effects of a peer support programme on
      adolescents' knowledge, attitudes and use of alcohol and tobacco. Year 7 students
      (average age 12 years) from three schools who offered the programme (n = 169) and
      from three schools without the programme (n = 157) completed a self-report
      assessment. Perceptions of their parents' and friends' use of alcohol and tobacco
      and attitudes towards the participants' use of these substances as well as the
      participants' own attitudes (preferences and norms) and use of the substances
      were assessed on three occasions; pre-intervention, post-intervention and at 6
      months follow-up. There were no significant effects of the programme on
      participants' knowledge, attitudes and use of alcohol and tobacco. Over time,
      participants in both groups reported increased enjoyment of alcohol, increased
      use of alcohol and tobacco and more lenient attitudes towards these substances.
      In conclusion, the peer support programme failed to show any positive influence
      on adolescents' knowledge, attitudes and use of alcohol and tobacco.

PMID- 12219739
TI  - Fifth annual conference on new and re-emerging infectious diseases.

PMID- 12219740
TI  - Madness.

PMID- 12219741
TI  - A profile of an HIV-and child-specific programme in New Orleans, Louisiana, USA.
AB  - Since the beginning of the AIDS epidemic, 4.3 million children under 15 years of
      age have been infected with HIV worldwide; in the year 2000 alone, the World
      Health Organization estimates that 600,000 children became HIV-infected.
      Ancillary services offer the potential to improve access to and retention in
      primary care through removal of barriers to care. Globally, ancillary services
      may actually represent a significant proportion of all care delivered to HIV
      infected children, particularly in the absence of expensive antiretroviral
      treatments. The purpose of this non-concurrent cohort study was to describe a
      population of HIV-infected children receiving ancillary services from an HIV- and
      family-specific ancillary service programme in New Orleans, Louisiana, USA. Forty
      two HIV-infected children ages newborn to 13 years were included in the study.
      The majority were between one and five years of age (50.0%), male (54.8%),
      African-American (88.1%), and perinatally infected (97.6%). Services were well
      utilized; delivery decreased with age and increased with severity of clinical
      disease. Improved retention, prescription of antiretroviral treatment and HIV
      related emergency room utilization were associated with ancillary service
      receipt. Ancillary services delivered by an HIV- and family-specific programme
      assist HIV-infected children to receive improved medical care. Ancillary services
      are a valuable adjunct to primary care, particularly in the complex care of the
      HIV-infected children from historically underserved populations.

PMID- 12219742
TI  - [An explanatory model of behavior toward mental illness].
AB  - OBJECTIVE: To evaluate a theoretical model designed to explain behaviors toward
      mental illness, considering some variables related to the construct. MATERIAL AND
      METHODS: A survey was conducted in 1996 on mental disorder beliefs, attitudes,
      and behavioral intentions. The sample population was stratified by socioeconomic
      status, age, and gender. Study subjects were 800 individuals from Mexico City's
      general population. A data collection instrument was constructed and validated,
      consisting of 120 Likert-type items with five options each. Data were coded and
      analyzed with the software package SPSS. Internal consistency of the scales was
      assessed using Cronbach's alpha and construct validity with factorial analysis.
      Student's t test and ANOVA were used to compare the groups in the different
      strata. RESULTS: The model allowed to confirm the predictive capacity of the
      causal chain connecting beliefs, attitudes, and intentions; nevertheless, other
      study variables did not contribute to explain it, and behavior was scarcely
      influenced by intentions, depending mainly on experimented necessity.
      CONCLUSIONS: Study findings constitute a basis to understand the attitudes of
      shame and fear usually related to mental illnesses, to plan efficient actions
      aimed at modifying them, and to design programs to promote mental health. The
      English version of this paper is available at:
      http://www.insp.mx/salud/index.html.

PMID- 12219743
TI  - [The introduction of the western psychiatry into Korea: from the mid seventeenth
      century to 1911, the time of Japanese forced annexation of Korea].
AB  - The object of this study is to investigate the routes of the introduction of the
      western psychiatric knowledges and practices in Korea. The historical documents
      including newspapers and governmental bulletins as well as articles and books on
      the history of the Korean medicine were examined and the results are as follows:
      The western knowledge about the brain anatomy and physiology were introduced from
      China by the enlightened Confucian and Taoistic scholars of Korea in the mid
      seventeenth century through the Chinese translations of the western science and
      medicine. Due to the lack of support for the scholars and even persecution by the
      ruling power to those who had great interests in the western thoughts including
      sciences, the western medical knowledges could not be actualized in practice.
      Thus, the active practices of western medicine were started in the late 19th
      century in Korea through the two routes; one, via Japanese military physicians
      and the other one, via the western missionary physicians. The psychiatry was
      lectured by Japanese psychiatrist in 1910 at the medical school of Tai-Han Unwon,
      the Korean governmental clinic and 1913 at the Severance medical school of Tai
      Han Uiwon, the Korean governmental clinic and in 1913 at the Severance medical
      school by the Australian psychiatrist, McLaren. As the independent department
      with the psychiatric ward, the first Dept. of Psychiatry was established in 1913
      at the colonial governmental clinic, Chosun Chondokbu-Uiwon, the former Tai-Han
      Ui-won. Medicine as well as psychiatry was introduced into Korea under the
      political atmosphere of one sided admiration for the western science. The
      attempts to combine the western medicine with the traditional Korean medicine
      could not be tolerated by both missionary physicians and the colonial regime.

PMID- 12219744
TI  - [Possibility in unification of oriental and western medicine education by
      combination of educational curricula].
AB  - The authors attempted a possibility of unification in the educational curricula
      of both Oriental and Western medical schools for the unification of two
      medicines. Historically the two medicines were originated from the most primitive
      state like instinctive method and we can say two medicines were entirely the
      same. However, after abrupt and current development of science in the 19th
      century by discovery of microscope and bacteria as well as cells, changed
      medicine into recent unbelievable current medicine from old ancient style
      medicine like Chinese Medicine which was just the remnant old medicine. The
      unification of educational curricula is thought to be possible to combine each
      other by technical adjustment from mutual understanding and cooperation for the
      most high quality of peoples lives. There were good equality to partial
      correspondences between two educational curricula around 90% at two pre-and
      schools from the study to analyse. The combined medicine is thought to be more
      efficient to the diagnosis and treatment of patients because of the effectiveness
      of Oriental medicine in certain disease conditions like chronic illness by
      acupuncture as a alternative medicine or herbs.

PMID- 12219746
TI  - Immunization registry progress--United States, 2002.
AB  - Immunization registries are confidential, population-based, computerized
      information systems that collect vaccination data about all children within a
      geographic area. By providing complete and accurate information on which to base
      vaccination decisions, registries are key tools to increase and sustain high
      vaccination coverage. Registries consolidate vaccination records of children from
      multiple health-care providers, identify children who are due or late for
      vaccinations, generate reminder and recall notices to ensure that children are
      vaccinated appropriately, and identify provider sites and geographic areas with
      low vaccination coverage. One of the national health objectives for 2010 is to
      increase to 95% the proportion of children aged <6 years who participate in fully
      operational, population-based immunization registries (objective 14.26). This
      report summarizes data from the calendar year 2001 Immunization Registry Annual
      Report (CY 2001 IRAR), a survey of registry activity among immunization programs
      in the 50 states and the District of Columbia (DC) that receive grant funding
      under Public Health Service Act 317b. Although these data indicate that
      approximately half of U.S. children aged <6 years are participating in a
      registry, achieving the national health objective will require increased
      immunization provider participation.

PMID- 12219745
TI  - Outbreak of measles--Venezuela and Colombia, 2001-2002.
AB  - Substantial progress has been made toward interrupting indigenous measles
      transmission in the Region of the Americas. In 2001, the number of confirmed
      measles cases in the region reached a record low of 537 cases, a 99% decrease
      since 1990. During 2001, the Dominican Republic and Haiti interrupted indigenous
      measles transmission successfully, ending known indigenous transmission of the D6
      measles virus genotype. This genotype, which had circulated widely in the Region
      of the Americas since 1995, caused nationwide outbreaks in Argentina, Bolivia,
      Brazil, the Dominican Republic, and Haiti during 1997-2001. In August 2001, a
      measles outbreak introduced by a traveler returning from Europe occurred in
      Venezuela and was exported to Colombia in 2002. This report describes the
      epidemiology of the outbreaks and control measures implemented by the ministries
      of health of Venezuela and Colombia.

PMID- 12219747
TI  - Progress toward poliomyelitis eradication--Angola, January 1998-June 2002.
AB  - Since the World Health Assembly resolved in 1988 to eradicate poliomyelitis, the
      estimated number of polio cases worldwide has declined >99%. Angola began polio
      eradication activities in 1996. Although polio eradication efforts have been
      hampered by the country's 27-year-long civil war, both the incidence of polio
      cases and the geographic circulation of poliovirus in Angola have decreased
      substantially. The cessation of hostilities on April 4, 2002, presents a new
      opportunity to reach populations that had been inaccessible and undervaccinated
      previously. This report summarizes progress made during January 1998-June 2002
      and highlights the remaining challenges to eradicating polio in Angola.

PMID- 12219748
TI  - West Nile virus activity--United States, August 21-28, 2002, and Illinois,
      January 1-August 27, 2002.
AB  - This report summarizes West Nile virus (WNV) surveillance data reported to CDC
      through ArboNET and by states and other jurisdictions as of 7:30 a.m. Mountain
      Daylight Time, August 28, 2002, and highlights WNV activity in Illinois.

PMID- 12219749
TI  - Immune tolerance and stroke: a turning point.

PMID- 12219750
TI  - Diffusion-weighted MRI: back to the future.

PMID- 12219751
TI  - Dementia after stroke: high incidence and intriguing associations.

PMID- 12219752
TI  - GPs in deprived areas do more out of hours work.

PMID- 12219753
TI  - Venezuela launches new campaign against dengue fever.

PMID- 12219754
TI  - US students face national examination on simulated patients.

PMID- 12219755
TI  - Depo-Provera contraceptive may increase risk of cardiovascular disease.

PMID- 12219756
TI  - Indian government denies health impact of brown cloud.

PMID- 12219757
TI  - Development of neurophysiology in the early twentieth century: Charles Scott
      Sherrington and The Integrative action of the nervous system.

PMID- 12219758
TI  - [The introduction of tobacco and the diffusion of smoking culture in Korea].
AB  - Since its introduction to Korea from Japan at the beginning of the seventeenth
      century, tobacco became very popular with an amazing rapidity among Koreans.
      Along with widespread cultivation of tobacco, smoking also became very popular
      among Koreans, regardless of their classes, ages, and sexes. On the other hand,
      other imported crops from America via Europe in the sam period, like sweet
      potato, potato, corn and tomato, did not enjoy such popularity in Korea. A long
      time after their introduction, Koreans began to cultivate these crops. Why did
      Koreans respond enthusiastically to the newly-imported tobacco? What kind of
      factors contributed to the rapid transmission of tobacco in Korea? This study
      examined the causes of rapid diffusion of the smoking population in three
      aspects. First was economic aspect. The farming of tobacco yielded a profit by
      selling it to Chinese. The climate and the soil of Korea fit for farming of
      tobacco. So the farm land of tobacco expanded gradually since the 18th century.
      Second was medical aspect. At first, many Koreans believed that smoking was
      helpful to digestion, expectoration, protecting coldness, and exterminating
      parasites. Afterwards, they believed smoking could encourage vitality and protect
      diseases. There was no reason of smoking cessation for the people's health in
      that the hazards of smoking were not well known to the commonage in those days,
      though a few intellectuals acknowledge its harm. Third was sociocultural aspect.
      We could trace the smoking culture of Chosun dynasty through arts, poems, and
      essays. The making of smoking culture made stable reproduction of smokers
      generation by generation. Especially, the smoking culture secured juvenile's
      smoking. Considering the three aspects above, we know that what reason the Decree
      of Ban of Smoking in Korea was not strict in comparison to that of China (Qing
      Dynasty), in which the violators were executed. The regulation of smoking by the
      government failed except controlling in sociocultural aspect. The government
      reinforced controlling of smoking culture in counteraction to the threat of
      collapse of the hierarchy of Chosun dynasty in 18th century.

PMID- 12219759
TI  - [Social status and role of students entering Jejoongwon: focus on Kyum-Rae Lee].
AB  - This study considers the social class and social role of the entering students of
      Jejoongwon at that time in light of its very first medical graduate, Kyum-Rae
      Lee. Foremost, Kyum-Rae Lee was confirmed to have been from a middle-class
      family. However, unlike other chungin-class families, his family belonged to the
      minority. He seemed to have entered medical school to seek opportunity to move up
      in social class by taking advantage of special government provisions, which
      allowed him to learn English and Western medicine. Afterwards, he performed
      heroic services in the peasant-war, proceeded up to administration and
      participated in the modernization of Great Han Empire. With his knowledge of
      Western concepts, he became involved in numerous social activities, such as
      organizing the Enlightenment Society and leading the Enlightenment Movement. In
      much the same way, most early students were from low-class background with
      exceptional personal abilities and were able to pass aptitude examinations. Such
      achievements allowed them to apply for positions in the military and
      administrative management. Ten years later, medical education to train medical
      professionals was revived with changes in attitudes of people of Chosun Dynasty
      toward Western medicine and with creation of formal medical study.

PMID- 12219760
TI  - Health problems and long-term unemployment.
AB  - The article deals with the relation between unemployment and health problems
      using as a case a local support project for long-term unemployed in northern
      Finland. Mass unemployment has increased competition on the labor market, and
      successful job-seekers must have a wider range of qualifications than before. As
      demands have intensified on the labor market, health has become a salient
      criterion in the recruitment process. At the same time the incidence of illness
      among long-term unemployed is surprisingly high. The situations of the project
      clients strongly indicate that health-related difficulties are one distinct risk
      factor for the long-term unemployed in finding work. We need new means for health
      promotion, more extensive psychosocial rehabilitation and local solutions for
      people who are unemployed.

PMID- 12219761
TI  - Globalisation and social policy.
AB  - This paper discusses six major themes: that economic and social issues are
      closely interdependent and that the appropriate stance is to work on both
      together, simultaneously; that though the threats from globalisation have been
      exaggerated, there can be substantial costs as well as considerable benefits;
      that constraints on national policy are significant but are less severe than is
      commonly considered; that the vitality-the vigour-of national and international
      political processes must be increased to cope effectively with the changes which
      are underway; that the private sector, unions and civil society have crucial
      roles in the provision of services and in advocating socially responsible values,
      standards and policies; and that one of the most effective means of addressing
      the erosion of national autonomy from globalisation is for countries to cooperate
      in setting and implementing shared objectives and international standards and
      establishing more global public goods.

PMID- 12219762
TI  - Use of standardized measures in agency based research and practice.
AB  - This article reviews criteria for social workers' selection and use of
      standardized outcome measures for practice and research. Issues related to
      reliability and validity are discussed. The utility of standardized Health
      Related Quality of Life (HRQL) measures, either generic or disease specific, is
      presented utilizing one measure, the SF-36+ Social Work, as an exemplar. The
      article concludes that such measures are viable and necessary for social work to
      demonstrate its value-added qualities in the emerging healthcare environment.

PMID- 12219763
TI  - Construction of a global assessment scale of family function, using a
      questionnaire.
AB  - Self-report questionnaires are commonly used in family research, but very little
      attention is paid to the specific measurement properties of the ordered
      categorical data recorded. The item responses of self-report questionnaires
      consist of ordered categories. The main property of this type of data is that the
      labels do not represent a mathematical value but only an order, i.e., one set of
      labels can be replaced by another set of increasing numbers of symbols. The non
      additivity of categorical data means that sum scores cannot be used as a global
      assessment of the variable. The aims of this study were to further develop the
      third version of the self-report questionnaire Family Adaptability and Cohesion,
      Evaluation Scales (FACES), for use in Sweden and to construct a global scale of
      family function for the variables cohesion and adaptability. The statistical
      methods used take account of the rank-invariant properties of ordered categorical
      data.

PMID- 12219764
TI  - Development of the Workload Analysis Scale (WAS) for the assessment and
      rehabilitation services of Ballarat Health Services.
AB  - This study describes the development of the Workload Analysis Scale (WAS),
      designed to predict the likely workload involved for social workers working with
      clients in the assessment and rehabilitation areas of Ballarat Health Services
      (BHS). Such a scale would allow more equitable case allocation, flagging of
      difficult cases, better work prioritisation, training of new staff and tracking
      changes over time. Items for the scale were developed in consultation with
      workers. Initially the scale consisted of 33 items divided into five subscales,
      relating respectively to treatment factors, demographics, psychosocial
      complexity, planned interventions and variable staff factors. Eight staff members
      of BHS contributed to the completion of the scale for 111 clients seen over a
      four month period on the rehabilitation and assessment wards. Initial analysis of
      the data led to a modification of the scale and subsequent satisfactory measures
      of reliability and validity.

PMID- 12219765
TI  - Discharge planning for complex paediatric cases.
AB  - The aim of this study was to identify the functions performed by social workers
      specifically engaged in paediatric discharge planning by undertaking a detailed
      analysis of discharge planning practice in forty cases referred to a specialist
      discharge planning team, at the Royal Children's Hospital, Melborne. A second aim
      was to identify the characteristics that distinguished complex cases from more
      routine cases. Discharge planning activity focused on the family, community and
      the organisation, with most cases requiring activity in all three areas. More
      complex cases were characterised by amount of social work time spent on the case,
      length of stay and number of discharge planner functions performed, but not
      number of prior admissions.

PMID- 12219766
TI  - The development of an Australian national classification system for social work
      practice in health care.
AB  - Australian Social Work, over recent years, has been challenged to develop a
      standardised and accurate classification system for social work interventions.
      The need for such a system arose through changes in funding arrangements based on
      the Diagnosis Related Groups (DRGs) treated within hospitals. In Australian
      hospitals, the mix of DRGs treated became known as its 'casemix.' These new
      funding arrangements made it necessary for Social Work to classify and measure
      activity with each patient to ensure continuing resource allocation to social
      work services in hospitals. A national Casemix Network was formed under the
      auspice of the Australian Association of Social Workers to develop a
      classification system. The Network worked collaboratively with other allied
      health professions to produce a generic framework for professional activities and
      also developed a classification of social work interventions. These activity
      classifications have been incorporated into procedure coding in Australian
      hospitals. The challenges associated with casemix funding required Social Work to
      address a number of philosophical and methodological issues related to
      classification of professional activities to ensure an outcome that recognised
      the unique contribution of Social Work to health care.

PMID- 12219767
TI  - A classification system of social problems: concepts and influence on GPs'
      registration of problems.
AB  - OBJECTIVES: (1) To test lists of problems in the three axes of well-being
      (physical, mental, and social) with the GPs' collaboration (2) To place the
      resulting classification in the context of other ones aiming at collecting data
      about psycho-social aspects of life (assessment, index and classification
      systems). (3) To test if GPs would be induced to record psychological and social
      problems more often in their everyday practice, after having been trained to look
      more closely at them, inter allia with the use of classification and codes.
      METHOD: The lists of problems have been initiated by the WHO Department of Mental
      Health and discussed at an international symposium; they were then tested on the
      field, first at an international level, then in Belgium. After discussion by 4
      Belgian GPs' Teaching Units, they were then improved. In all surveys concerned,
      general practitioners were asked to collaborate in three ways: opening their
      usual medical records and collaborating to prospective phases, including one
      "test phase," i.e., a training session, recording problems with the use of coding
      lists, and looking for the proper code. Retrospective and prospective approaches
      were used both before and after this test phase. RESULTS: (1) The original lists
      of problems have been improved on the basis of the findings in medical files and
      in the survey. (2) A conceptual framework is presented for recording social
      problems, either in everyday practice (i.e., in health records) or in research
      settings, e.g., for social surveys. It is biaxial: domains and types of problem.
      (3) Training GPs for using such a coding system drastically increases the number
      of psycho-social problems, but only during the prospective phases. In the long
      run older habits prevail again; only the overall number of contacts mentioning a
      reason increases, together with the number of "other" reasons for encounter
      (requests, ...). CONTENTS: (1) Main concepts (section 1). (2) Various tools for
      measuring psychosocial problems and well-being (section 2). (3) New conceptual
      fanmework for a classification of psychosocial problems ( 2.2.3). (4) Using the
      lists: influence on MDs' recording propensity (section 3).

PMID- 12219768
TI  - Health care and social work education in a changing world.
AB  - This article examines two major challenges that beset contemporary social work
      education, namely, rapid and dramatic macro-level changes that are occurring in
      the social, political, economic and demographic realms and, also, the slow speed
      at which curriculum changes occur in institutions of higher education. Primarily
      employing managed care as an example, a series of recommendations are offered to
      improve social work education concerning health care. Among them are more
      efficient mechanisms for introducing curriculum changes, greater emphasis on
      research and evaluations skills, systematic monitoring of health care programs,
      preparation of public impact reports, better utilization of modern information
      technologies, and the introduction of mini-courses that can be adapted readily to
      emerging health care and educational needs.

PMID- 12219769
TI  - The buck stops where? Contracting, service delivery and the challenge to provide
      responsive services.
AB  - This paper discusses the impact of contract-based purchasing on the delivery of
      social and health services to families in New Zealand. The paper arose out of
      research conducted by the authors into the effectiveness of certain human service
      interventions. It begins with an outline of the agency in which the research took
      place. It presents a brief overview of the development of contracting and then
      considers four key issues raised by this development from both the international
      literature and from the authors' experience of researching a social service
      agency. These issues are: defining what is to be purchased, accountability
      mechanisms, specificity/fragmentation and partial funding. The paper identifies
      that central components of the first two issues are informational, the third is
      about control and the fourth is about reducing government spending and extending
      state control over the activities of the not-for-profit sector.

PMID- 12219770
TI  - The business model and social work: a conundrum for social work practice.
AB  - The economic and social philosophies of the "New Right" which emphasise
      individualism and self-fulfillment have become wide-spread. In the last two
      decades it has grown particularly strong in Western societies. Self-fulfillment
      of the individual now commands its own moral imperative, and promotes the
      shutting out of the greater issues and concerns (political, historical and
      religious) that transcend the self. This paper examines the impact of "New Right"
      ideologies on social workers and social work practice, with particular reference
      to social workers in New Zealand's largest mental health institution, Porirua
      Hospital. It argues that a life course approach is necessary to understand social
      variations in health. It explores the accumulation of risk for the
      underprivileged in the market environment, with its concomitant constraints on
      human services. The paper reviews the inherent and fundamental conflict of
      objectives in the ethical positioning of social organizations, as against those
      of the ew Right." Finally, the paper argues for social and economic policies that
      would defend the socio-economically disadvantaged against an accumulation of risk
      in the critical periods of their life. It highlights survival strategies for
      social work in a marginalizing practice environment.

PMID- 12219771
TI  - Social work and health restructuring in Canada and Finland.
AB  - The health care systems in Canada and Finland are currently in the process of
      restructuring. Responsibility for care has increasingly shifted to ill persons
      themselves and to their families and friends. Reduced hospital stays, service
      privatization and user fees have been implemented to some degree in both
      countries. These changes are reverberating throughout Finnish and Canadian
      societies, affecting not only users of health care but also the labour force in
      health workplaces. Health social workers, at the front line with clients, have
      experienced new issues which have impacted on their practice with ill persons and
      their families. In an environment of health care restructuring, they have needed
      to draw upon their repertoires of knowledge, skills and community networks in
      order to respond. At the same time, social workers noted that there is a leaner
      package of health and social service benefits to support patients and families.
      Social workers have tried to adapt and find new opportunities to practice social
      work in the changed environment. This small study, initially conducted as a pilot
      for a larger study, compared the experiences of social workers in Canada and
      Finland and the perceived impacts of health restructuring on their clients. The
      findings, seen within the context of changing societal and institutional
      environments, can help us to better understand some of the impacts of health
      restructuring on social work and social workers in hospitals and local health
      centres. Indirectly and directly, these changes also affect clients in the health
      care system, those whose needs remain uppermost in the delivery of social work
      services.

PMID- 12219772
TI  - Delivering health care services in the community: a multidisciplinary
      perspective.
AB  - The Canadian health care system has shifted away from its traditional emphasis on
      acute care in-patient services, to increasing dependence on community-based
      services. A major implication is that education for work in this new environment
      will need to be reconceptualized, and those already in the system will have to
      examine their assumptions and alter their approach to patient care. This paper
      reports the results of a study which examines the attitudes, educational
      preparation, skills sets, and perceptions of "community" among social workers,
      occupational therapists, nurses and physiotherapists. The results should inform
      social work and other health educators about relevant theoretical and practical
      preparation for work in an environment which increasingly emphasizes multiple
      skills, community partnerships and coordinated care.

PMID- 12219773
TI  - Searching for a valid animal model of hemolytic uremic syndrome.

PMID- 12219774
TI  - Apoptotic rate in peripheral T-cell lymphomas. A study using a tissue microarray
      with validation on full tissue sections.
AB  - Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin
      lymphomas with a wide spectrum of clinicopathologic features, and apoptosis
      mechanisms may have a role in lymphomagenesis. We assessed apoptotic rate (AR) in
      112 PTCLs using a tissue microarray developed in our laboratory and a modified
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. The
      mean AR was 1.47% +/- 1.38% for the entire group of PTCLs (range, 0.06%-5.15%),
      and AR varied significantly among different tumor types. In mycosis fungoides,
      the mean AR was 0.74%; angioimmunoblastic T-cell lymphoma, 1.02%; PTCL, not
      otherwise specified, 1.38%; cutaneous anaplastic large cell lymphoma (ALCL),
      1.41%; anaplastic lymphoma kinase protein (ALK)-negative ALCL, 1.43%; extranodal
      natural killer/T-cell lymphoma of nasal type, 2.04%; ALK-positive ALCL, 2.95%;
      and enteropathy-type T-cell lymphoma, 3.06%. Mean AR was higher in PTCL with
      large cell vs small/medium cell morphologic features (1.66% +/- 1.1% vs 0.99% +/-
      1.0%). In a subset of 33 PTCLs, the tissue microarray results comparedfavorably
      with those obtained in full tissue sections. We conclude that the highest ARs in
      PTCLs are found in enteropathy-type T-cell lymphoma and ALK-positive ALCL, and
      that AR can be assessed reliably by using a tissue microarray.

PMID- 12219775
TI  - Langerhans cell histiocytosis immunohistochemical expression of fascin, a
      dendritic cell marker.
AB  - Langerhans cell histiocytosis (LCH) is a clonal disorder believed to be
      derivedfrom cells of the dendritic system. Fascin, a 55-kd actin-bundling
      protein, represents a highly selective marker for dendritic cells of lymphoid
      tissues and peripheral blood and is involved in the formation of dendritic
      processes in maturing epidermal Langerhans cells. Since lesional cells of LCH may
      represent Langerhans cells arrested at an early stage of activation,
      immunohistochemical expression offascin in epidermal Langerhans cells and in the
      lesional cells of 34 cases of LCH was evaluated in paraffin sections using an
      immunoalkaline phosphatase technique. Though epidermal Langerhans cells were
      nonreactive for fascin, lesional cells in all LCH cases exhibited
      immunoreactivityforfascin, CD1a, and S-100 protein. Variation in staining
      intensity was observed in some cases, possibly reflecting differences in cell
      maturation or activation. Involved tissues included bone, soft tissue, lymph
      node, thyroid, orbit, and extradural cranial tissue. Immunoreactivity of lesional
      cells of LCH for fascin supports their derivation from cells of the dendritic
      system and represents another alteration in the phenotype of Langerhans cells
      that is associated with maturation, migration, culture, or clonal expansion.

PMID- 12219776
TI  - Determination of cytokine responses using a multiplexed fluorescent microsphere
      immunoassay.
AB  - We used a multiplexedfluorescent microsphere immunoassay to develop a sandwich
      capture assay to assess simultaneously the production of thymus helper (TH) 1-
      and TH2-type cytokines in tissue culture supernatant obtained from stimulated
      peripheral blood mononuclear cells. The assay then was used to assess the
      cytokine production of patients with hyperimmunoglobulinemia E syndrome and in
      cord blood from neonates. The multiplexed assay has a reportable range of less
      than 10 to 50,000 pg/mL. For linearity and recovery studies, R2 values for the 6
      cytokines ranged from 0.988 to 0.999 for samples spiked with known concentrations
      of recombinant cytokine standards and for patient samples. The assay showed good
      specificity, with little cross-reactivity between cytokines. Results from
      supernatants of Staphylococcus aureus-stimulated peripheral blood mononuclear
      cells obtainedfrom 6 patients with hyperimmunoglobulinemia E syndrome showed
      significantly less interferon (IFN)-gamma production than cells from healthy
      control subjects. Cord blood cells from neonates produced significantly less
      interleukin 12 and IFN-gamma than cells from adults in group B streptococci
      stimulated mononuclear cells. The fluorescent multiplexed microsphere immunoassay
      can be used to quantitate multiple cytokines from 1 sample and should be useful
      for further understanding of the cytokine role in disease.

PMID- 12219777
TI  - The measurement of cardiac markers: where should we focus?
AB  - Cardiac markers are presently a hot topic, with active debate on their use. They
      now have a major role for cost-effective management of acute chest pain and
      suspected acute coronary syndrome. The laboratory has a pivotal role in proper
      selection and interpretation of available markers, depending on the creation of
      evidence-based knowledge about test utilization and sources of variation. This
      article reviews this knowledge in the field of biomarkers determination and
      summarizes the major analytic and clinical issues, with reference to various
      recent recommendations of laboratory medicine and cardiology expert groups.

PMID- 12219778
TI  - Gnotobiotic piglets develop thrombotic microangiopathy after oral infection with
      enterohemorrhagic Escherichia coli.
AB  - Oral infection with enterohemorrhagic Escherichia coli (EHEC) may cause severe
      enteritis, followed in up to 10% of cases by an extraintestinal complication, the
      hemolytic uremic syndrome (HUS). HUS is characterized by a triad of symptoms:
      anemia, thrombocytopenia, and acute renalfailure due to thrombotic
      microangiopathy. EHEC produces several virulence factors, among which a family of
      phage-encoded cytotoxins, called Shiga toxin 1 and Shiga toxin 2, seems to be
      most important. However, since an appropriate animal model is not available,
      pathogenicity of these emerging enteric pathogens is still poorly understood.
      Germ-free gnotobiotic piglets infected orally with an O1577:H7 or an O26:H11 EHEC
      wild-type isolate, both producing Shiga toxin 2, developed intestinal and
      extraintestinal manifestations of EHEC disease, including thrombotic
      microangiopathy in the kidneys, the morphologic hallmark of HUS in humans. Thus,
      gnotobiotic piglets are suitable to further study the pathophysiology of EHEC
      induced HUS. It can be expected that data obtainedfrom this animal model will
      improve our current standard of knowledge about this emerging infectious disease.

PMID- 12219779
TI  - Leukocyte-reduced transfusions in cardiac surgery results of an implementation
      trial.
AB  - An implementation trial of leukocyte-reduced transfusions in cardiac surgery
      (primary coronary artery bypass graft and valve replacement) was performed from
      July to December 1998; comparisons were made with data from the same period in
      1997. Patients from both periods were similar in important preoperative and
      intraoperative variables (age, sex, weight, number of units of RBCs transfused,
      ejection fraction). The mean total number of complications was statistically
      significantly decreasedfrom 0.26 complications per patient in the non-leukocyte
      reduced to 0.19 in the leukocyte-reduced recipients. Overall, the mean +/- ISD
      costs of care per patient decreasedfrom 1997 ($27,615 +/- $33,973) to 1998
      ($27,038 +/- $24,107). Mean costs decreased $1,700 per patient for recipients of
      leukocyte-reduced blood in 1998 compared with recipients of non-leukocyte-reduced
      blood in 1997 Mean costs increased $4,000 per patient in patients who did not
      receive transfusions in 1998 compared with 1997. Hospitalization costs decreased
      when leukocyte-reduced transfusions were implemented for patients undergoing
      cardiac surgery in our institution. Implementation of leukocyte reduction may be
      cost neutral or cost saving in at least some settings.

PMID- 12219780
TI  - Restriction fragment length polymorphism and polymerase chain reaction: HLA-DQA1
      and polymarker analysis of blood samples from transfusion recipients.
AB  - The effect of blood transfusion on DNA profiles of an individual is a significant
      issue in the forensic context. In the present study, the effects of blood
      transfusion in 5 recipients were studied by performing restriction fragment
      length polymorphism and polymerase chain reaction HLA-DQA1 and Polymarker (LDLR,
      GYPA, HBGG, D7S8, and GC) assays (Roche Molecular Systems, Branchburg, NJ) on
      serial posttransfusion blood samples. Pretransfusion and posttransfusion DNA
      profiles of all 5 recipients were consistent with no evidence of the donor
      genetic material. Currently used DNA profiling techniques in forensic science are
      reliable and informative for paternity and identity purposes in situations
      involving transfusion of 1 or 2 U of blood up to 24 hours posttransfusion.

PMID- 12219781
TI  - Expression of cytolytic lymphocyte-associated antigens in pulmonary lymphomatoid
      granulomatosis.
AB  - Paraffin-embedded lung wedge biopsy specimens from 14 patients with pulmonary
      lymphomatoid granulomatosis (LYG) were analyzed using immunoperoxidase stains
      specific for T cell- and natural killer cell-associated antigens. Nine cases had
      a minor population of CD20+ large B-cells (B-cell LYG) amidst a background of CD3
      and betaF1-immunoreactive T cells. In 8 of the 9 B-cell LYG cases, the majority
      of the background T lymphocytes had a cytotoxic phenotype as defined by the
      expression of CD8 and the cytotoxic granule proteins TIA-1 (granule membrane
      protein 17) and granzyme B. Five cases lacked CD20+ large cells and, instead,
      showed predominantly CD3+ and betaF1 + T cells (T-cell LYG). Whereas the small,
      medium, and large atypical lymphocytes were all positive for CD3 and betaF1 in
      the T-cell LYG cases, immunoreactivity for CD8, TIA-1, and granzyme B was limited
      to the small lymphocytes, with a distribution indistinguishable from that seen in
      B-cell LYG. These findings indicate that LYG is composed of a heterogeneous group
      of lymphoproliferative disorders that share, as unifying features, a relative
      paucity of neoplastic cells and a prominent reactive infiltrate rich in cytolytic
      lymphocytes.

PMID- 12219782
TI  - Location-guided screening of liquid-based cervical cytology specimens: a
      potential improvement in accuracy and productivity is demonstrated in a
      preclinical feasibility trial.
AB  - A 2-armed, masked study was performed on 1,275 AutoCyte PREP (TriPath,
      Burlington, NC) slides. Manual screening (current practice [CP]) was compared
      with automated screening with location-guided screening (LGS) using the AutoPap
      system with the SlideWizard 2 automated review microscopy station (TriPath).
      Cytologic adjudication determined "truth" for each slide. LGS identified more
      abnormal cases at all interpretive levels and classified abnormalities more
      specifically. For high-grade squamous intraepithelial lesions and above, the
      overall sensitivity of appropriate triage to pathologist review was 98.4% for LGS
      and 91.1% for CP. The appropriate triage for all abnormal cases was 92.1% for LGS
      and 87.9% for CP. The potential exists for more accurate and productive cytologic
      interpretation using this system, which requires no manual screening of a portion
      of slides and only limited review of another portion of "predotted" slides.

PMID- 12219783
TI  - Evaluation of HER-2/neu immunohistochemical assay sensitivity and scoring on
      formalin-fixed and paraffin-processed cell lines and breast tumors: a comparative
      study involving results from laboratories in 21 countries.
AB  - Variation in assay sensitivity was studied in more than 90 laboratories that
      assayed 4formalin-fixed, paraffin-processed breast and ovarian carcinoma cell
      lines with graded levels of HER-2/neu protein overexpression and known levels of
      HER-2/neu gene amplification, in addition to breast carcinomas fixed and
      processed in the laboratories. Main methods were the HercepTest (DAKO, Ely,
      England) and individualized protocols using a polyclonal antibody and the CB11
      clone. While the proportion of laboratories achieving appropriate results with
      the HercepTest was significantly higher than for participants using other assays,
      laboratories using other assays showed significant improvement in the second
      assessment run. The level of agreement in evaluations by 26 laboratories using
      the HercepTest was excellent on cell lines and tumors and was significantly
      greater than that achieved by the remaining 41 laboratories using other
      immunohistochemical methods. While laboratories using the DAKO HercepTest had the
      highest level of reproducibility in assay sensitivity and evaluation, the
      significant improvement in results by laboratories using other antibodies in the
      second assessment run suggests that stringent quality control and an ongoing
      quality assurance program using a standard reference material have the potential
      to improve the reliability of immunohistochemical assays for HER-2/neu,
      regardless of the antibody used.

PMID- 12219784
TI  - Fine-needle aspiration biopsy of nonteratomatous germ cell tumors of the
      mediastinum.
AB  - We assessed the usefulness of fine-needle aspiration biopsy (FNAB) in the
      diagnosis of mediastinal germ cell tumors (GCTs). In the archives of 3 pathology
      departments, we found records of 7 patients with mediastinal GCTs who underwent
      mediastinal FNAB as part of the diagnostic workup. The FNAB smears, results of
      the immunocytochemical analysis, the corresponding histologic findings, and the
      clinical charts were reviewed. All patients were men (age range, 24-44 years;
      mean, 32 years). One patient had a history of testicular mixed GCT 10 years
      earlier. The 6 primary mediastinal GCTs consisted of 3 seminomas and 3 yolk sac
      tumors. Based on the cytologic features and immunocytochemicalfindings, a
      cytologic diagnosis of GCT was made in 5 cases, including the case of metastatic
      GCT In 2 cases, the differential diagnosis was between poorly differentiated
      carcinoma and GCT Results of ancillary studies were noncontributory in 1 case,
      and the aspirate of the second case demonstrated extensive necrosis. Our findings
      demonstrate that a diagnosis of mediastinal GCT, primary or secondary, can be
      established with a high degree of accuracy on the basis of FNAB.
      Immunocytochemical analysis helps confirm the diagnosis.

PMID- 12219785
TI  - Does the level of E-cadherin expression correlate with the primary breast
      carcinoma infiltration pattern and type of systemic metastases?
AB  - Relationships between membrane E-cadherin reactivity of invasive carcinoma, a
      dyshesive growth pattern, and lobular carcinoma-type systemic metastases were
      studied in 295 breast carcinomas and 57 patients with lobular carcinoma systemic
      metastases. There were 143 pure lobular carcinomas, 80 mixed (lobular and ductal)
      carcinomas, and 72 pure ductal carcinomas. Two (7%) of 30 mixed, predominantly
      lobular carcinomas, 23 (61%) of 38 mixed carcinomas, and 8 (67%) of 12 mixed,
      predominantly ductal carcinomas had E-cadherin staining in more than 10% of the
      lobular carcinoma cells. Lobular carcinoma-type systemic metastases were
      identified in 45 cases (38 [84%], pure lobular; 5 (11%], mixed; 2 [4%], pure
      ductal). No E-cadherin staining was found in 42 (98%) of 43 lobular carcinomas in
      cases of lobular carcinoma-type sYstemic metastases and all 57 cases of lobular
      carcinoma systemic metastases. Absent cell-to-cell adhesion seems to be a
      necessary property of carcinoma cells to facilitate permeation through tissue
      planes and produce characteristic lobular carcinoma-type systemic metastases. The
      level of decreased E-cadherin expression at which a dyshesive growth pattern
      emerges in primary breast carcinomas may be less than the level associated with
      lobular carcinoma-type systemic metastases.

PMID- 12219786
TI  - Cytopathology of malignant melanoma in conventional and liquid-based smears.
AB  - We evaluated 62fine-needle aspiration (FNA) biopsy specimens of metastatic
      malignant melanoma (MM) from 62 patients and compared 84 smears with the
      corresponding tissue sections. Melanin is found more often in FNA smears than in
      corresponding tissue sections of metastatic MM but is significantly less abundant
      in smears. Melanin is present more often in liquid-based than in conventional
      smears. Pseudoinclusions were almost twice as frequent in tissue sections as in
      corresponding aspirates, regardless of the preparation method. There was no
      statistical difference for cell type or cytoplasmic features in the tissue
      sections and aspirates or between the type of preparation and/or stain used. With
      the exception of melanin, direct comparison of liquid-based and conventional
      smears showed higher cellularity in the former as the only difference.

PMID- 12219787
TI  - Carcinoma extent in prostate needle biopsy tissue in the prediction of whole
      gland tumor volume in a screening population.
AB  - Increasing prostate tumor volume has been shown to correlate with numerous
      adverse prognostic indicators for patients with prostate carcinoma The ability to
      predict tumor volume from pretreatment parameters is potentially critical in the
      stratification of patients for different management strategies. We assessed the
      capacity of preoperative variables to predict tumor volume in 100 men diagnosed
      with prostate cancer in a prostate-specific antigen (PSA)-based screening
      program. Preoperative information included total serum PSA concentration and
      needle biopsy tissue variables, including Gleason score, number of positive
      cores, linear extent of carcinoma in millimeters, greatest percentage of
      carcinoma (in a single core), total percentage of carcinoma (all cores), presence
      of perineural invasion, and percentage of high-grade carcinoma. The postoperative
      end point was total tumor volume in radical prostatectomy tissue, calculated by
      image analysis. We determined independently significant factors and generated a
      predictive modelfor whole gland tumor volume. Total tumor volume was related
      significantly in multivariate analysis to 3 preoperative variables: linear extent
      of carcinoma, exponential number of positive cores, and serum PSA. A predictive
      model generated based on these 3 variables accounted for only 65% of the natural
      deviance of the data owing to data-point scatter for individual patients,
      suggesting that additional variables are needed to more accurately predict tumor
      volume. Findings highlight the importance of reporting quantitative measures of
      tumor amount in prostate needle biopsy specimens; several measures of tumor
      extent (vs 1 measure) provide maximal information on prostate cancer size.

PMID- 12219788
TI  - Differential expression of high-affinity melatonin receptors (MT1) in normal and
      malignant human breast tissue.
AB  - Melatonin is a pineal hormone that strongly inhibits the growth of breast cancer
      cells in vitro and in vivo. We report thefirst use of immunohistochemical
      analysis to determine the distribution of the high-affinity melatonin receptor
      subtype, MTI, in human breast tissue, the hypothalamic suprachiasmatic nucleus,
      and skin. The MT1 antibody, which is specific for the cytoplasmic portion of the
      receptor, produced cytoplasmic staining in normal-appearing breast epithelial
      cells and ductal carcinoma cells; stromal cells, myoepithelial cells, and
      adipocytes were nonreactive. The majority of nonneoplastic samples (13/19 [68%])
      were negative to weakly positive, while moderate to strong reactivity was seen in
      most cancer samples (49/65 [75%]). Thus, although MT1 receptors were detectable
      in normal and malignant breast epithelium, high receptor levels occurred more
      frequently in tumor cells (P < .001), and tumors with moderate or strong
      reactivity were more likely to be high nuclear grade (P < .045). These findings
      may have implications for the use of melatonin in breast cancer therapy.

PMID- 12219790
TI  - CD117 in soft tissue sarcomas.

PMID- 12219789
TI  - Histologic follow-up of people with celiac disease on a gluten-free diet: slow
      and incomplete recovery.
AB  - To assess histologic recovery in response to gluten withdrawal in celiac disease,
      158 patients seen in our hospital during a 15-year period underwent follow-up
      small intestine biopsies (SIBs) within 2 years after starting a gluten-free diet;
      further SIBs were done if villous atrophy was present. A modified Marsh
      classification was used (IIIA, partial villous atrophy; IIIB, subtotal villous
      atrophy; IIIC, total villous atrophy). Of patients with Marsh IIIA, IIIB, or IIIC
      lesions, histologic remission was seen in 65.0% within 2 years, 85.3% within 5
      years, and 89.9% in long-term follow-up. Eleven patients (7.0%) with persisting
      (partial) villous atrophy had symptoms and signs of malabsorption and were
      considered to have refractory celiac disease; 5 of them developed an enteropathy
      associated T-cell lymphoma. Children recovered up to 95% within 2 years and 100%
      in the long-term. Histologic recovery in celiac disease after starting a gluten
      free diet takes time and is incomplete or absent in a substantial subgroup of
      patients (10.1% villous atrophy after 5 years). Systematic follow-up of patients
      with celiac disease and the malabsorption syndrome and secondary complications is
      needed.

PMID- 12219791
TI  - KIT activation in soft tissue sarcomas.

PMID- 12219792
TI  - Toward a unified account of spacing effects in explicit cued-memory tasks.
AB  - Memory for repeated items improves when presentations are spaced during study.
      This effect is found in memory tasks using different types of material,
      paradigms, and participant populations. Although several explanations have been
      proposed, none explains the presence of spacing effects in cued-memory tasks for
      unfamiliar stimuli. Two experiments assessed the spacing effect on a yes-no
      recognition-memory task using nonwords and words as targets. The main results
      showed that changing the font between repeated occurrences of targets at study
      removed the spacing effect for nonwords only. A 3rd experiment using lexical
      decision showed that the font manipulation reduced repetition priming of nonwords
      when items were repeated at Lag 0. These results suggest that short-term
      perceptual priming supports spacing effects in cued-memory tasks for unfamiliar
      stimuli.

PMID- 12219793
TI  - Word frequency and receiver operating characteristic curves in recognition
      memory: evidence for a dual-process interpretation.
AB  - Dual-process models of the word-frequency mirror effect posit that low-frequency
      words are recollected more often than high-frequency words, producing the hit
      rate differences in the word-frequency effect, whereas high-frequency words are
      more familiar, producing the false-alarm-rate differences. In this pair of
      experiments, the authors demonstrate that the analysis of receiver operating
      characteristic (ROC) curves provides critical information in support of this
      interpretation. Specifically, when participants were required to discriminate
      between studied nouns and their plurality reversed complements, the ROC curve was
      accurately described by a threshold model that is consistent with recollection
      based recognition. Further, the plurality discrimination ROC curves showed
      characteristics consistent with the interpretation that participants recollected
      low-frequency items more than high-frequency items.

PMID- 12219794
TI  - Revisiting the picture-superiority effect in symbolic comparisons: do pictures
      provide privileged access?
AB  - In 4 experiments, symbolic comparisons were investigated to test semantic-memory
      retrieval accounts espousing processing advantages for picture over word stimuli.
      In Experiment 1, participants judged pairs of animal names or pictures by
      responding to questions probing concrete or abstract attributes (texture or size,
      ferocity or intelligence). Per pair, attributes were salient or nonsalient
      concerning their prerated relevance to animals being compared. Distance (near or
      far) between attribute magnitudes was also varied. Pictures did not significantly
      speed responding relative to words across all other variables. Advantages were
      found forfar attribute magnitudes (i.e., the distance effect) and salient
      attributes. The distance effect was much less for salient than nonsalient
      concrete-attribute comparisons. These results were consistently found in
      additional experiments with increased statistical power to detect modality
      effects. Our findings argue against dual-coding and some common-code accounts of
      conceptual attribute processing, urging reexamination of the assumption that
      pictures confer privileged access to long-term knowledge.

PMID- 12219795
TI  - Covert operations: orthographic recoding as a basis for repetition priming in
      word identification.
AB  - When a word is generated from a semantic cue, coincident orthographic
      visualization of that word may cause priming on a subsequent perceptual
      identification test. A task was introduced that required subjects to visualize
      the orthographic pattern of auditorily presented words. When used at study, this
      task produced a pattern of priming similar to that produced by a generate study
      task. When used at test, equal priming on the orthographic task was produced by
      read and generate study tasks but not by a generate study task that failed to
      invite orthographic visualization. Priming on perceptually based word
      identification tests that results from a generate study episode may be largely
      due to orthographic recoding of the target rather than to conceptual processing.

PMID- 12219796
TI  - A decisional component of holistic encoding.
AB  - It has been proposed (see, specifically, M. J. Farah, K. D. Wilson, M. Drain, &
      J. N. Tanaka, 1998) that human faces are used in cognition as undifferentiated
      wholes. General recognition theory (GRT; F. G. Ashby & J. T. Townsend, 1986) is
      used to represent hypotheses regarding the possible sources for the behavioral
      evidence supporting holistic representation. Specifically, it is suggested that
      holism can be understood in terms of violations of informational independence,
      informational separability, or decisional separability, as these constructs are
      defined in GRT. Stimuli were presented upright, inverted, and in an encoding task
      that emphasized the meaningful nature of the stimuli. Patterns of performance
      (recognition hit rates) were consistent with prior studies. However, there were
      only a handful of violations of informational separability. Instead, consistent
      violations of decisional separability suggested a decisional basis for holistic
      effects.

PMID- 12219797
TI  - The effect of category variability in perceptual categorization.
AB  - Exemplar and distributional accounts of categorization make differing predictions
      for the classification of a critical exemplar precisely halfway between the
      nearest exemplars of 2 categories differing in variability. Under standard
      conditions of sequential presentation, the critical exemplar was classified into
      the most similar, least variable category, consistent with an exemplar account.
      However, if the difference in variability is made more salient, then the same
      exemplar is classified into the more variable, most likely category, consistent
      with a distributional account. This suggests that participants may be strategic
      in their use of either strategy. However, when the relative variability of 2
      categories was manipulated, participants showed changes in the classification of
      intermediate exemplars that neither approach could account for.

PMID- 12219798
TI  - Adaptive categorization in unsupervised learning.
AB  - In 3 experiments, the authors provide evidence for a distinct category-invention
      process in unsupervised (discovery) learning and set forth a method for observing
      and investigating that process. In the 1st 2 experiments, the sequencing of
      unlabeled training instances strongly affected participants' ability to discover
      patterns (categories) across those instances. In the 3rd experiment, providing
      diagnostic labels helped participants discover categories and improved learning
      even for instance sequences that were unlearnable in the earlier experiments.
      These results are incompatible with models that assume that people learn by
      incrementally tracking correlations between individual features; instead, they
      suggest that learners in this study used expectation failure as a trigger to
      invent distinct categories to represent patterns in the stimuli. The results are
      explained in terms of J. R. Anderson's (1990, 1991) rational model of
      categorization, and extensions of this analysis for real-world learning are
      discussed.

PMID- 12219799
TI  - Exemplar and prototype models revisited: response strategies, selective
      attention, and stimulus generalization.
AB  - J. D. Smith and colleagues (J. P. Minda & J. D. Smith, 2001; J. D. Smith & J. P.
      Minda, 1998,2000; J. D. Smith, M. J. Murray, & J. P. Minda, 1997) presented
      evidence that they claimed challenged the predictions of exemplar models and that
      supported prototype models. In the authors' view, this evidence confounded the
      issue of the nature of the category representation with the type of response rule
      (probabilistic vs. deterministic) that was used. Also, their designs did not test
      whether the prototype models correctly predicted generalization performance. The
      present work demonstrates that an exemplar model that includes a response-scaling
      mechanism provides a natural account of all of Smith et al.'s experimental
      results. Furthermore, the exemplar model predicts classification performance
      better than the prototype models when novel transfer stimuli are included in the
      experimental designs.

PMID- 12219800
TI  - Determiner selection in noun phrase production.
AB  - In 3 experiments, native speakers of German named pictures of 1 or 2 objects by
      producing singular or plural noun phrases consisting of a definite gender-marked
      determiner and a noun. When singular and plural determiners differed (masculine
      and neuter gender), naming latencies were longer for plural utterances than for
      singular utterances. By contrast, when singular and plural determiners were
      identical (feminine gender), no such effect was obtained. When participants
      produced bare nouns, the Gender x Number interaction disappeared. This pattern
      indicates that during the production of plural definite-determiner noun phrases,
      singular and plural determiners compete for selection. The resulting constraints
      on number and gender processing in noun phrase production are discussed in the
      framework of models of language production.

PMID- 12219801
TI  - Strategic effects in associative priming with words, homophones, and
      pseudohomophones.
AB  - G. Lukatela and M. T. Turvey (1994a) showed that at a 57-ms prime-presentation
      duration, the naming of a visually presented target word (frog) is primed not
      only by an associate word (toad) but also by a homophone (towed) and a
      pseudohomophone (tode) of the associate. At a 250-ms prime presentation, priming
      with the homophone was no longer observed. In Experiment 1, the authors
      replicated these priming effects in the Dutch language. Next, the authors
      extended the priming paradigm to a word/legal-nonword lexical decision task
      (Experiments 2 and 3) and a word/pseudohomophone decision task (Experiment 4).
      Phonologically mediated associative priming was observed in all conditions with
      pseudohomophonic primes but not with homophonic primes. The latter did not prime
      at a 250-ms prime-presentation time and at 57 ms in the word/pseudohomophone
      task.

PMID- 12219802
TI  - Sentence context, word recognition, and repetition blindness.
AB  - When the sentence She ran her best time yet in the rice last week is displayed
      using rapid serial visual presentation, viewers sometimes misread rice as race
      (M. C. Potter, A. Moryadas, I. Abrams, & A. Noel, 1993). Seven experiments
      combined misreading and repetition blindness (RB) paradigms to determine whether
      misreading of a word because of biasing sentence context represents a genuine
      perceptual effect. In Experiments 1-4, misreading a word either caused or
      prevented RB for a downstream word, depending on whether orthographic similarity
      was increased or decreased. Additional experiments examined temporal parameters
      of misreading RB and tested the hypothesis that RB results from reconstructive
      memory processes. Results suggest that the effect of prior context occurs during
      perception.

PMID- 12219803
TI  - Aggregation in memory of episodic influences on rule-guided decisions.
AB  - The authors confirmed E. Z. Rothkopf and M. L. Dashen's (1995) finding that
      specific problem context, such as thematic surface features, forms associative
      connections with deep problem features and thus speeds particular decisions
      (particularization). In 5 experiments, using a 3-bit decision task and pre
      memorized decision rules, the authors found that the ability of a situational
      context to reinstate was decreased by its replacement by another modal surface
      context. Context reinstatement, as measured by decision speed, depended on both
      global and recent local densities of specific problem features linked to a
      particular decision. The authors' results are consistent with J. R. Anderson and
      L. J. Schooler's (1991) needs/odds analysis and suggest a push-down file model
      for diverse context influences as a mechanism for responding to changing
      situational demands.

PMID- 12219804
TI  - The nativist-empiricist controversy in the context of recent research on spatial
      and quantitative development.
AB  - Demonstrations of cognitive competence in preschool children and infants played
      an important role in the waning influence of Piagetian theory and the rise of
      nativism. Arguments and data favoring modularity have further buttressed the
      casefor nativism. This article reviews evidence concerning early competence and
      modularity in the spatial and quantitative domains, as well as the role of
      experience in development. This evidence provides little reason to support
      nativist claims in either domain.

PMID- 12219805
TI  - Show me the features! Understanding recognition from the use of visual
      information.
AB  - We propose an approach that allows a rigorous understanding of the visual
      categorization and recognition process without asking direct questions about
      unobservable memory representations. Our approach builds on the selective use of
      visual information in recognition and a new method (Bubbles) to depict and
      measure what this information is. We examine three face-recognition tasks
      (identity, gender, expressive or not) and establish the componential and holistic
      information responsible for recognition performance. On the basis of this
      information, we derive task-specific gradients of probability for the allocation
      of attention to the different regions of the face.

PMID- 12219806
TI  - Objects and events in the attentional blink.
AB  - When two visual targets, T1 and T2, are presented in rapid succession, detection
      or identification of T2 is almost universally degraded by the requirement to
      attend to T1 (the attentional blink, or AB). One interesting exception occurs
      when T1 is a brief gap in a continuous letter stream and the task is to
      discriminate its duration. One hypothesized explanation for this exception is
      that an AB is triggered only by attention to a patterned object. The results
      reported here eliminate this hypothesis. Duration judgments produced no AB
      whether the judged duration concerned a short gap in the letter stream
      (Experiment 1) or a letter presentedfor slightly longer than others (Experiment
      2). When identification of an identical longer letter T1 was required (Experiment
      3), rather than a duration judgment, the AB was reestablished Direct perceptual
      judgments of letter streams with gaps embedded showed that whereas brief gaps
      result in the percept of a single, briefly hesitating stream, longer gaps result
      in the percept of two separate streams with a separating pause. Correspondingly,
      an AB was produced in Experiment 4, when participants were required to judge the
      duration of longer T1 gaps. We propose that, like spatially separated objects,
      temporal events are parsed into discrete, hierarchically organized events. An AB
      is triggered only when a new attended event is defined, either when a long pause
      creates a new perceived stream (Experiment 4) or when attention shifts from the
      stream to the letter level (Experiment 3).

PMID- 12219807
TI  - Unconscious masked priming depends on temporal attention.
AB  - The cognitive processes at work in masked priming experiments are usually
      considered automatic and independent of attention. We provide evidence against
      this view. Three behavioral experiments demonstrate that the occurrence of
      unconscious priming in a number comparison task is determined by the allocation
      of temporal attention to the time window during which the prime-target pair is
      presented. Both response-congruity priming and physical repetition priming vanish
      when temporal attention is focused away from this time window. These findings are
      inconsistent with the concept of a purely automatic spreading of activation
      during masked priming.

PMID- 12219808
TI  - Memory-load interference in syntactic processing.
AB  - Participants remembered a short set of words while reading syntactically complex
      sentences (object-extracted clefts) and syntactically simpler sentences (subject
      extracted clefts) in a memory-load study. The study also manipulated whether the
      words in the set and the words in the sentence were of matched or unmatched types
      (common nouns vs. proper names). Performance in sentence comprehension was worse
      for complex sentences than for simpler sentences, and this effect was greater
      when the type of words in the memory load matched the type of words in the
      sentence. These results indicate that syntactic processing is not modular,
      instead suggesting that it relies on working memory resources that are used for
      other nonsyntactic processes. Further, the results indicate that similarity-based
      interference is an important constraint on information processing that can be
      overcome to some degree during language comprehension by using the coherence of
      language to construct integrated representations of meaning.

PMID- 12219809
TI  - Variability and detection of invariant structure.
AB  - Two experiments investigated learning of nonadjacent dependencies by adults and
      18-month-olds. Each learner was exposed to three-element strings (e.g., pel-kicey
      jic) produced by one of two artificial languages. Both languages contained the
      same adjacent dependencies, so learners could distinguish the languages only by
      acquiring dependencies between the first and third elements (the nonadjacent
      dependencies). The size of the pool from which the middle elements were drawn was
      systematically varied to investigate whether increasing variability (in theform
      of decreasing predictability between adjacent elements) would lead to better
      detection of nonadjacent dependencies. Infants and adults acquired nonadjacent
      dependencies only when adjacent dependencies were least predictable. The results
      point to conditions that might lead learners to focus on nonadjacent versus
      adjacent dependencies and are importantfor suggesting how learning might be
      dynamically guided by statistical structure.

PMID- 12219810
TI  - Exemplar theory's predicted typicality gradient can be tested and disconfirmed.
AB  - One of exemplar theory's central predictions concerns the shape of typicality
      gradients. The typicality gradient it predicts is a consequence of its exemplar
      based comparisons and appears no matter how the theory is evaluated. However,
      this predicted typicality gradient does not fit the empirical typicality
      gradients obtained in an influential version of the dot-distortion category task,
      and this is true even when the exemplar model is made more flexible and
      mathematically powerful. Thus, exemplar theory is disconfirmed in this domain of
      categorization. In contrast, prototype theories are consistent with the
      empirically obtained typicality gradients.

PMID- 12219811
TI  - Attentional mechanisms linking rejection to hostile reactivity: the role of "hot"
      versus "cool" focus.
AB  - Drawing on the hot-cool systems analysis of self-regulation, we examined whether
      attentionalfocus mediates the negativity of cognitive-affective reactions to
      interpersonal rejection. The hypothesis was that whereas a hot, arousing focus to
      representing rejection experiences should increase anger-hostility, accessing the
      cool system through distraction and distancing should attenuate such responses.
      Participants imagined an autobiographical rejection experience, focusing either
      on their physiological and emotional reactions (hot focus) or on the physical
      setting of the experience (cool focus). Participants in a third condition
      received no specific attentional instructions. Both implicit and explicit
      measures showed that hostile thoughts and feelings were attenuated in the cool
      focus compared with the hot-focus condition. The findings support the adaptive
      value of activating a cooling strategy under hot, arousing conditions that
      otherwise elicit automatic, hot-system responses.

PMID- 12219812
TI  - Learning where to look for danger: integrating affective and spatial information.
AB  - Although not previously addressed by researchers of spatial cognition or affect,
      the combination of spatial and affective information is essential for many
      approach and avoidance behaviors, and thus for survivaL We provide the first
      evidence that through incidental experience, people form representations that
      capture correlations between affective and spatial information. Participants were
      able to do so even when the correlation was weak, they were not told to look for
      the correlation, and the stimuli varied on multiple other dimensions besides
      valence. In addition, people were more sensitive to the presented correlation
      when stimuli were negative than when they were positive. This asymmetry in
      representation may stem from underlying differences in the activation functions
      for positive and negative hedonic information processing.

PMID- 12219813
TI  - Inhibition and superconditioning.
AB  - Superconditioning is said to occur when learning an association between a
      conditioned stimulus (CS) and unconditioned stimulus (US) isfacilitated by
      pairing the CS with the US in the presence of a previously established
      conditioned inhibitor. Previous demonstrations of superconditioning have been
      criticized because their control conditions have allowed alternative
      interpretations. Using a within-subjects autoshaping procedure, the present study
      unambiguously demonstrated superconditioning. The results support the view that
      super-conditioning is the symmetric opposite of blocking.

PMID- 12219814
TI  - Are you looking at me? Eye gaze and person perception.
AB  - Previous research has highlighted the pivotal role played by gaze detection and
      interpretation in the development of social cognition. Extending work of this
      kind, the present research investigated the effects of eye gaze on basic aspects
      of the person-perception process, namely, person construal and the extraction of
      category-related knowledge from semantic memory. It was anticipated that gaze
      direction would moderate the efficiency of the mental operations through which
      these social-cognitive products are generated. Specifically, eye gaze was
      expected to influence both the speed with which targets could be categorized as
      men and women and the rate at which associated stereotypic material could be
      accessed from semantic memory. The results of two experiments supported these
      predictions: Targets with nondeviated (i.e., direct) eye gaze elicited
      facilitated categorical responses. The implications of these findings for recent
      treatments of person perception are considered.

PMID- 12219815
TI  - The phonological-similarity effect differentiates between two working memory
      tasks.
AB  - Working memory is a set of interactive cognitive processes that maintain
      information on-line and available for analysis. Part of the system is specialized
      for maintaining verbal information, a core component of which is thought to be a
      phonological store. On the basis of the study of patients with acquired brain
      lesions, this store has been localized to the supramarginal and angular gyri of
      the speech-dominant hemisphere, and some functional neuroimaging studies support
      this localization. However, other imaging studies localize the phonological store
      in a more dorsal region of the parietal lobe. To reconcile these findings, we
      examined the phonological-similarity effect in two different tasks. A
      phonological-similarity effect was observed only in the task that involved
      sequential presentation and explicit verbal rehearsal. We conclude that at least
      one possible source of the differences in brain activation between different
      working memory tasks may be differences in phonological processing.

PMID- 12219816
TI  - A prospective study of some effects of aircraft noise on cognitive performance in
      schoolchildren.
AB  - Before the opening of the new Munich International Airport and the termination of
      the old airport, children near both sites were recruited into aircraft-noise
      groups (aircraft noise at present or pending) and control groups with no aircraft
      noise (closely matched for socioeconomic status). A total of 326 children (mean
      age = 10.4 years) took part in three data-collection waves, one before and two
      after the switch-over of the airports. After the switch, long-term memory and
      reading were impaired in the noise group at the new airport. and improved in the
      formerly noise-exposed group at the old airport. Short-term memory also improved
      in the latter group after the old airport was closed. At the new airport, speech
      perception was impaired in the newly noise-exposed group. Mediational analyses
      suggest that poorer reading was not mediated by speech perception, and that
      impaired recall was in part mediated by reading.

PMID- 12219817
TI  - Infant timekeeping: attention and temporal estimation in 4-month-olds.
AB  - Four-month-old infants were exposed to sequences in which a 2-s light stimulus
      alternated with dark interstimulus periods whose length was manipulated to be 3
      or 5 s. A predictable on-off pattern occurred for eight trials, but the light
      stimulus was omitted on the ninth trial. Infants showed heart rate responses on
      the omission trial that were closely synchronized with the expected recurrence of
      the stimulus. In addition, these heart rate patterns were observed predominantly
      in infants who had previously shown high levels of sustained attention in
      pretests with visual stimuli. These findings indicate remarkable precision in
      infants' estimation of time intervals, and suggest that the link between time
      estimation and attentional processes is present in early infancy.

PMID- 12219818
TI  - Lexical neighborhoods and the word-form representations of 14-month-olds.
AB  - The degree to which infants represent phonetic detail in words has been a source
      of controversy in phonology and developmental psychology. One prominent
      hypothesis holds that infants store words in a vague or inaccurate form until the
      learning of similar-sounding neighbors forces attention to subtle phonetic
      distinctions. In the experiment reported here, we used a visual fixation task to
      assess word recognition. We present the first evidence indicating that, infact,
      the lexical representations of 14- and 15-month-olds are encoded in fine detail,
      even when this detail is not functionally necessary for distinguishing similar
      words in the infant's vocabulary. Exposure to words is sufficient for well
      specified lexical representations, even well before the vocabulary spurt. These
      results suggest developmental continuity in infants' representations of speech:
      As infants begin to build a vocabulary and learn word meanings, they use the
      perceptual abilities previously demonstrated in tasks testing the discrimination
      and categorization of meaningless syllables.

PMID- 12219819
TI  - Retinal flow is sufficient for steering during observer rotation.
AB  - How do people control locomotion while their eyes are simultaneously rotating? A
      previous study found that during simulated rotation, they can perceive a straight
      path of self-motion from the retinal flow pattern, despite conflicting
      extraretinal information, on the basis of dense motion parallax and reference
      objects. Here we report that the same information is sufficient for active
      control ofjoystick steering. Participants steered toward a target in displays
      that simulated a pursuit eye movement. Steering was highly inaccurate with a
      textured ground plane (motion parallax alone), but quite accurate when an array
      of posts was added (motion parallax plus reference objects). This result is
      consistent with the theory that instantaneous heading is determined from motion
      parallax, and the path of self-motion is determined by updating heading relative
      to environmental objects. Retinal flow is thus sufficient for both perceiving
      self-motion and controlling self-motion with a joystick; extraretinal and
      positional information can also contribute, but are not necessary.

PMID- 12219820
TI  - Photopolymerizable hydrogels for tissue engineering applications.
AB  - Photopolymerized hydrogels are being investigated for a number of tissue
      engineering applications because of the ability to form these materials in situ
      in a minimally invasive manner such as by injection. In addition, hydrogels,
      three-dimensional networks of hydrophilic polymers that are able to swell large
      amounts of water, can be made to resemble the physical characteristics of soft
      tissues. Hydrogel materials also generally exhibit high permeability and good
      biocompatibility making, these materials attractive for use in cell encapsulation
      and tissue engineering applications. A number of hydrogel materials can be formed
      via photopolymerization processes mild enough to be carried out in the presence
      of living cells. This allows one to homogeneously seed cells throughout the
      scaffold material and to form hydrogels in situ. This review presents advantages
      of photopolymerization of hydrogels and describes the photoinitiators and
      materials in current use. Applications of photopolymerized hydrogels in tissue
      engineering that have been investigated are summarized.

PMID- 12219821
TI  - Photoencapsulation of osteoblasts in injectable RGD-modified PEG hydrogels for
      bone tissue engineering.
AB  - Poly(ethylene glycol) (PEG) hydrogels were investigated as encapsulation matrices
      for osteoblasts to assess their applicability in promoting bone tissue
      engineering. Non-adhesive hydrogels were modified with adhesive Arg-Gly-Asp (RGD)
      peptide sequences to facilitate the adhesion, spreading, and, consequently,
      cytoskeletal organization of rat calvarial osteoblasts. When attached to hydrogel
      surfaces, the density and area of osteoblasts attached were dramatically
      different between modified and unmodified hydrogels. A concentration dependence
      of RGD groups was observed, with increased osteoblast attachment and spreading
      with higher RGD concentrations, and cytoskeleton organization was seen with only
      the highest peptide density. A majority of the osteoblasts survived the
      photoencapsulation process when gels were formed with 10% macromer, but a
      decrease in osteoblast viability of approximately 25% and 38% was seen after 1
      day of in vitro culture when the macromer concentration was increased to 20 and
      30wt%, respectively. There was no statistical difference in cell viability when
      peptides were added to the network. Finally, mineral deposits were seen in all
      hydrogels after 4 weeks of in vitro culture, but a significant increase in
      mineralization was observed upon introduction of adhesive peptides throughout the
      network.

PMID- 12219822
TI  - Photocrosslinkable polyvinyl alcohol hydrogels that can be modified with cell
      adhesion peptides for use in tissue engineering.
AB  - Photoactive polyvinyl alcohol hydrogels (PVA) have been investigated for use as
      tissue engineering scaffolds. These materials allow in situ polymerization for
      minimally invasive implantation methods. The mechanical properties of these
      materials can be tailored for a variety of soft tissue applications. The Young's
      modulus and ultimate tensile strength of PVA hydrogels are increased with
      increasing polymer concentration, and highly elastic hydrogels can be formed by
      altering the number of crosslinkable groups per chain. Fibroblasts homogeneously
      seeded within 3 mm thick PVA hydrogels remained viable throughout 2 weeks in
      culture, with no differences in viability across the thickness of the hydrogel.
      Cells seeded within the PVA hydrogels also produce extracellular matrix proteins,
      as indicated by the production of hydroxyproline during culture. Intrinsically
      cell non-adhesive, these PVA hydrogels were functionalized with the cell-adhesive
      peptide RGDS and found to support the attachment and spreading of fibroblasts in
      a dose-dependent manner. These results suggest that photopolymerizable PVA
      hydrogels are promising for tissue engineering applications.

PMID- 12219823
TI  - Photocrosslinking characteristics and mechanical properties of diethyl
      fumarate/poly(propylene fumarate) biomaterials.
AB  - The development of tissue engineered materials for the treatment of large bone
      defects would provide attractive alternatives to the autografts, allografts, non
      degradable polymers, ceramics, and metals that are currently used in clinical
      settings. To this end, poly(propylene fumarate) (PPF), a viscous polyester
      synthesized from diethyl fumarate (DEF), has been studied for use as an
      engineered bone graft. We have investigated the photocrosslinking of PPF
      dissolved in its precursor, DEF, using the photoinitiator bis(2,4,6
      trimethylbenzoyl) phenylphosphine oxide (BAPO) and low levels of ultraviolet
      light exposure. A three factor, 2 x 2 x 4 factorial design was developed,
      studying the effects of PPF number average molecular weight, BAPO initiator
      content, and DEF content upon photocrosslinking characteristics and mechanical
      properties. Uncured DEF/PPF solution viscosity fell over three orders of
      magnitude as DEF content was increased from 0% to 75%. The exothermic
      photocrosslinking reaction released low levels of heat, with no more than 160J/g
      released from any formulation tested. As a result, the maximum photocrosslinking
      temperature remained below 47 degrees C for all samples. Both sol fraction and
      swelling degree generally increased with increasing DEF content. Compressive
      mechanical properties were within the range of trabecular bone, with the
      strongest samples possessing an elastic modulus of 195.3 +/- 17.5 MPa and a
      fracture strength of 68.8 +/- 9.4MPa. Finally, the results indicate that PPF
      crosslinking was facilitated at low DEF precursor concentrations, but hindered at
      higher precursor concentrations. These novel DEF/PPF solutions may be preferred
      over pure PPF as the basis for an engineered bone graft because they (1) exhibit
      reduced viscosity and thus are easily handled, (2) form polymer networks with
      compressive strength at fracture suitable for consideration for trabecular bone
      replacement, and (3) may be readily fabricated into solids with a wide range of
      structures.

PMID- 12219824
TI  - Synthesis and characterization of injectable, water-soluble copolymers of
      tertiary amine methacrylates and poly(ethylene glycol) containing methacrylates.
AB  - Several homopolymers and copolymers of 2-(diethylamino)ethyl methacrylate (DEAEM)
      and poly(ethylene glycol) methyl ether methacrylate (PEGMEM) were synthesized
      using anionic polymerization initiated by potassium t-butoxide. The polymers were
      characterized by average molecular weight, polydispersity and monomeric unit
      composition. A very narrow molecular weight distribution was achieved with a well
      controlled composition. The glass transition temperatures and compositions of the
      copolymers followed a Gordon-Taylor relationship. The water solubility and
      biocompatibility of the copolymers was compared to their parent homopolymers to
      determine if the addition of a poly(ethylene glycol) group was sufficient to
      solubilize the polymers in aqueous buffer solutions and to increase the
      biocompatibility of the polymers. These water-soluble, injectable cationic
      copolymers have potential applications in gene delivery as well as other
      biomaterial applications.

PMID- 12219825
TI  - Sustained delivery of human growth hormone from a novel gel system: SABER.
AB  - PURPOSE: The purpose of this study was to evaluate the release of recombinant
      human growth hormone (rhGH) from a novel non-polymeric sustained release system,
      SABER. METHODS: The SABER system consists of sucrose acetate isobutryate, a
      solvent and a polymeric release modifier. Spray dried formulations of zinc
      complexed rhGH in sodium bicarbonate containing sucrose and polysorbate 20 were
      homogenized with various SABER systems (10% w/v rhGH) and assessed in vitro and
      in vivo (rat studies). The effect of protein to sucrose ratio in the spray dried
      formulation and a release modifier, poly-D,L-lactic acid (PLA), in the SABER
      system, on the initial release was investigated along with the effect of dose
      volume. RESULTS: The in vitro release studies with rhGH SABER suspensions
      indicate that increasing the sucrose content from 2 to 5 mg/ml in the rhGH
      formulations increased the initial release (24 h) from 78.0% to 93.5%. When the
      protein formulation was held constant and 1.0% w/w PLA was added to the solvent
      phase, the initial release was reduced from 78.0% to less than 5.0%. The initial
      release in vivo after subcutaneous administration (SC) in rats (15 mg/kg rhGH)
      decreased with increasing PLA content (1.0% w/w PLA, Cmax = 342.8 ng/ml; 10% w/w
      PLA, Cmax = 35.4 ng/ml), while increased sucrose content increased both the
      initial release (AUC(0-2) days) and persistence (AUC(2-7) days) over the 7 days
      from 64.2 to 228.4 ng day/ml (total AUC). A linear dose response (rhGH serum
      levels) was observed after SC administration of different rhGH SABER volumes
      greater than 100 microl. Histological examination of the injection sites
      indicated a mild inflammatory response similar to that observed after injection
      of PLA microspheres. CONCLUSIONS: The addition of PLA reduced the initial release
      rate of protein release from SABER, while increasing the sucrose content of the
      protein formulation yielded increased rhGH persistence. These results demonstrate
      that the SABER delivery system allows weight-based dosing at volumes greater than
      100 microl to achieve sustained release of intact rhGH in vivo for at least 7
      days.

PMID- 12219826
TI  - Development of an injectable, in situ crosslinkable, degradable polymeric carrier
      for osteogenic cell populations. Part 1. Encapsulation of marrow stromal
      osteoblasts in surface crosslinked gelatin microparticles.
AB  - This study investigated the temporary encapsulation of rat marrow stromal
      osteoblasts in surface crosslinked gelatin microparticles. Cells were
      encapsulated in uncrosslinked gelatin microparticles of average diameter of 630
      microm containing approximately 53 cells. Gelatin microparticles were crosslinked
      to shell thicknesses of approximately 75 microm via exposure to 1 mM
      dithiobis(succinimidylpropionate) (DSP) solution for 15 min or 5 mm DSP solution
      for 5 min for the production of microparticles dispersing approximately 60 min
      after placement into a physiologic fluid at 37 degrees C. Formed microparticles
      were placed into culture wells at a cell seeding density of 5.3 x 10(4) cells/cm2
      and, following the degradation and/or dissolution of gelatin, the cells were
      cultured in the presence of osteogenic supplements for 28 days. Samples were
      taken at specified time points and analyzed by a DNA assay for cell number and a
      3H-thymidine incorporation assay for proliferative potential. Samples were also
      obtained and analyzed at several time points by alkaline phosphatase,
      osteocalcin, and mineralization assays for early and late phenotypic expression
      markers of osteoblastic differentiation. The measurements from the different
      assays for encapsulated cells (EC) in uncrosslinked and crosslinked gelatin
      microparticles were normalized with the cell numbers from the DNA assay and
      compared with those for nonencapsulated control cells. The results demonstrated
      that the marrow stromal cells survived the encapsulation procedure in
      uncrosslinked gelatin microparticles and also retained their proliferative
      potential and osteoblastic phenotype over a 28 day period, although at a slightly
      lower level than the nonencapsulated cells. The results further showed that the
      marrow stromal cells survived the encapsulation in crosslinked gelatin
      microparticles prepared via exposure to 5mm DSP for 5 min and also retained their
      proliferative potential and osteoblastic phenotype over a 28 day period, but at a
      slightly lower level than the EC in uncrosslinked gelatin microparticles. In
      contrast, exposure to 1 mM DSP for 15 min led to severely limited cell viability
      and phenotypic expression probably due to the increased crosslinking time. These
      results suggest that temporary encapsulation of cells in gelatin microparticles
      may protect cells from short-term environmental effects such as those associated
      with the crosslinking of an injectable polymeric carrier for bone tissue
      engineering.

PMID- 12219827
TI  - Development of an injectable, in situ crosslinkable, degradable polymeric carrier
      for osteogenic cell populations. Part 2. Viability of encapsulated marrow stromal
      osteoblasts cultured on crosslinking poly(propylene fumarate).
AB  - The effect of temporary encapsulation of rat marrow stromal osteoblasts in
      crosslinked gelatin microparticles on cell viability and proliferation was
      investigated in this study for microparticles placed on a crosslinking
      poly(propylene fumarate) (PPF) composite over a 7 day time period. Encapsulated
      cells were seeded on crosslinking PPF composites at times up to 10 min following
      initiation of the crosslinking reaction, and also on fully crosslinked PPF
      composites and tissue culture polystyrene controls, with a cell seeding density
      of 5.3 x 10(4) cells/cm2. The crosslinked PPF composite exhibited an average gel
      point of 10.3 min and an average maximum crosslinking temperature of 47.5 degrees
      C. Cell viability and proliferation were assessed by DNA and 3H-thymidine assays
      and the results were compared with those for nonencapsulated cells. The results
      showed that the addition time of cells to a crosslinking PPF composite had a
      large effect on cell viability and proliferation for both encapsulated and
      nonencapsulated cells with more surviving cells added at later time points. Most
      importantly, the temporary encapsulation of cells significantly enhanced cell
      viability at earlier time points. The data indicate that the presence of gelatin
      microparticles does not affect the crosslinking of a PPF composite. They further
      suggest that the temporary encapsulation of cells in crosslinked gelatin
      microparticles may preserve the viability of cells contained in an actively
      crosslinking PPF composite used as an injectable polymeric scaffold serving also
      as a carrier for osteogenic cell populations.

PMID- 12219828
TI  - Development of an injectable, in situ crosslinkable, degradable polymeric carrier
      for osteogenic cell populations. Part 3. Proliferation and differentiation of
      encapsulated marrow stromal osteoblasts cultured on crosslinking poly(propylene
      fumarate).
AB  - This study investigated the effect of temporary encapsulation of rat marrow
      stromal osteoblasts in crosslinked gelatin microparticles on long-term cell
      proliferation and phenotypic expression for microparticles placed on crosslinking
      poly(propylene fumarate) (PPF) composites using N-vinyl pyrollidinone (N-VP) as a
      crosslinking agent over a 28 day time period. Encapsulated cells (ECs) were
      seeded on actively crosslinking PPF composites 6 min after initiation of the
      crosslinking reaction, and also on fully crosslinked PPF composites and tissue
      culture polystyrene controls, with a cell seeding density of 5.3 x 10(4)
      cells/cm2. Composites prepared with three PPF:N-VP ratios were examined: 1:0.5,
      1:0.1, and 1:0.05. Samples were taken at specified time points and analyzed by
      DNA, 3H-thymidine, alkaline phosphatase, osteocalcin, and calcium assays, and the
      measurements were compared with those for nonencapsulated cells (NCs). The
      results showed that encapsulated marrow stromal cells exhibited much higher
      viability, proliferation, and phenotypic expression when placed on crosslinking
      PPF composites than NCs. The assay results for ECs on crosslinking PPF composites
      were also similar to those on fully crosslinked PPF composites. The data further
      demonstrated that the PPF:N-VP ratio had no effect on the viability,
      proliferation, or phenotypic expression of the ECs. These results suggest that
      cells encapsulated in crosslinked gelatin microparticles may be part of an
      injectable, in situ crosslinkable, biodegradable polymeric composite for bone
      tissue engineering applications.

PMID- 12219829
TI  - Stereocomplexes based on poly(lactic acid) and insulin: formulation and release
      studies.
AB  - Diastereoisomeric complexes of insulin with D-poly(lactic acid) (D-PLA) or
      stereocomplexes of D- and L-PLA entrapping insulin were discovered. The complexes
      were spontaneously formed when insulin and D-PLA were mixed together in
      acetonitrile solution. Complexes of insulin-D-PLA formed a microparticulate
      precipitate after a few hours in the solution. The porous 1-3 microm precipitate,
      which contained both insulin and D-PLA, was insoluble in solvents that dissolve
      isotactic PLA, and had an additional transition temperature at 169 degrees C.
      When suspending these particles in buffer solution of pH 7.4, 37 degrees C,
      insulin was constantly released for a few weeks. L-PLA or D,L-PLA did not form a
      precipitate with insulin, which indicates stereospecificity to the complex
      formation. Microparticulates were also obtained when L-PLA was added to the D-PLA
      insulin solution. In this case two types of complexes, D-PLA-insulin and D-PLA-L
      PLA complexes, were formed. These macromolecular stereocomplexes may form the
      onset of the development of a new generation of controlled release systems for
      peptides and proteins, by molecular complexation with enantiomeric polymers.

PMID- 12219831
TI  - Design of an injectable system based on bioerodible polyanhydride microspheres
      for sustained drug delivery.
AB  - The fabrication, morphological characterization, and drug release kinetics from
      microspheres of three bioerodible polyanhydrides, poly[1,6-bis(p
      carboxyphenoxy)hexane] (poly(CPH)), poly(sebacic anhydride) (poly(SA)), and the
      copolymer poly(CPH-co-SA) 50:50 (CPH:SA 50:50) is reported. The fabrication
      technique yields microspheres with different morphologies for each of the three
      polymers studied, ranging from very smooth exterior surfaces for poly(CPH) to
      coarse surface roughness with large pores for poly(SA). Release profiles for the
      model drug, p-nitroaniline are also different for each polymer. The release
      profile from poly(CPH) has a large initial burst and shows little additional
      release after 2 days. The release from poly(SA) is nearly zero-order and lasts
      for about 8 days. The release profile from CPH:SA 50:50 shows a relatively small
      burst and then exhibits zero-order release for about I month. The different
      release profiles are attributed to both polymer erosion rates and drug
      distribution characteristics of the microspheres. Tailored release profiles of a
      burst followed by zero-order release are obtained by appropriately combining the
      microspheres. This technique enables independent modulation of both the burst and
      the zero-order release rate by varying the number of poly(CPH) and poly(SA)
      microspheres respectively. Additionally, the zero-order release can be extended
      from about a week to a month by including CPH:SA 50:50 microspheres.

PMID- 12219830
TI  - Development and applications of injectable poly(ortho esters) for pain control
      and periodontal treatment.
AB  - Poly(ortho esters) with a low glass transition temperature are semi-solid
      materials so that therapeutic agents can be incorporated at room temperature,
      without the use of solvents, by a simple mixing procedure. When molecular weights
      are limited to < 5 kDa, such materials are directly injectable using a needle
      size no larger than 22 gauge. Somewhat hydrophilic polymers can be produced by
      using the diketene acetal 3,9-diethylidene-2,4,8,10-tetraoxaspiro[5.5]undecane
      and triethylene glycol (TEG), while hydrophobic materials can be produced by
      using the diketene acetal and 1,10-decanediol. Molecular weight can be
      reproducibly controlled by using an excess of the diol, or by use of an alcohol
      that acts as a chain-stopper. Erosion rates can be controlled by varying the
      amount of latent acid incorporated into the polymer backbone. Toxicology studies
      using the TEG polymer have been completed and have shown that the polymer is non
      toxic. Toxicology studies using the decanediol polymer are underway. Development
      studies using the TEG polymer aimed at providing a sustained delivery of an
      analgesic agent to control post-surgical pain are under development and human
      clinical trials using the decanediol polymer for the treatment of periodontitis
      are also underway.

PMID- 12219832
TI  - A novel polyethylene depot device for the study of PLGA and P(FASA) microspheres
      in vitro and in vivo.
AB  - Polymer microspheres (0.5-5.0 microm) are difficult to characterize in vivo
      because they degrade, migrate, and are endocytosed. A novel polyethylene mesh
      pouch containing microspheres allowed for retrieval of degraded polymeric
      products from rats without affecting the rate of degradation. Pouches containing
      poly(lactic-co-glycolic acid) (PLGA) or poly(fumaric-co-sebacic acid) (P(FASA))
      microspheres were implanted intramuscularly, subcutaneously, and
      intraperitoneally and analyzed after 3, 7, 14, and 28 days. In vivo, subcutaneous
      or intraperitoneal implants experienced an immediate mass loss and a delayed
      decrease in molecular weight (Mw). Intramuscular implants behaved similarly to in
      vitro samples, decreasing in Mw immediately and lagging in mass loss. These
      results suggest that mass loss, which is usually dependent on Mw loss in vitro,
      may be directly due to enzymatic, rather than hydrolytic, degradation
      subcutaneously and intraperitoneally, while intramuscular implants appear to be
      mostly dependent on hydrolytic cleavage. This observation is further supported by
      histology. Additional experiments on pouches loaded with PLGA microspheres
      encapsulating osteoprotegerin, a protein drug used to prevent bone resorption,
      revealed that use of the device prevented the artifactual polymer compression
      inherent to microsphere centrifugation during release studies and allowed for the
      extraction of active protein from microspheres implanted for 3 days in vivo.

PMID- 12219834
TI  - Ankyrins, multifunctional proteins involved in many cellular pathways.
AB  - Ankyrins, originally discovered as components of the erythrocyte membrane
      appeared to be a family of animal proteins encoded in mammalian cells by three
      related genes. Developmentally regulated, tissue specific posttranscriptional
      processing generates a great variety of isoforms which seem to play specific role
      in various cells and subcellular structures, being involved, for example, in
      membrane skeleton organisation, ionic transport, maintenance of cell polarity as
      well as cell-cell adhesion regulation. The interaction between the membrane
      skeleton and cytoplasmic domains of transmembrane proteins plays a fundamental
      role in membrane integrity and stability as well as in many cellular processes.
      Once the cDNA sequence of red blood cell ankyrin was determined it became clear
      that "ankyrin-repeat" motifs are present in many proteins whose function is
      rather unrelated to the membrane skeleton, e.g. transcription factors. Ankyrins
      are a multigene family of intracellular, structural proteins that link several
      integral membrane proteins and the spectrin-based membrane cytoskeleton. The
      anion exchanger, Na+-K+ ATPase, a voltage dependent Na+ channel, an Na+/Ca2+
      exchanger, and adhesion molecules have been reported to interact with ankyrin in
      nonerythroid cells. Ankyrin was first found to link integral membrane proteins to
      the underlying spectrin-actin based membrane skeleton in the human erythrocyte.
      It was subsequently described in a variety of vertebrate cells and tissues,
      including brain, epithelia, and skeletal muscle. Variable cellular localisation
      of these membrane proteins may be possible due to different relative affinities
      of various isoforms of ankyrin for target proteins.

PMID- 12219833
TI  - New polymeric carriers for controlled drug delivery following inhalation or
      injection.
AB  - Inhalation is gaining increasing acceptance as a convenient, reproducible, and
      non-invasive method of drug delivery to the lung tissue and/or the systemic
      circulation. However, sustained drug release following inhalation remains
      elusive, due in part to the lack of appropriate materials designed specifically
      for use in the lungs to control the release of bioactive compounds. To address
      this problem, we have synthesized a new family of ether-anhydride copolymers
      composed entirely of FDA-approved monomers, including polyethylene glycol (PEG).
      Sebacic acid, a hydrophobic monomer, was copolymerized with PEG in order to
      produce water-insoluble polymers capable of providing continuous drug release
      kinetics following immersion in an aqueous environment. Various amounts of PEG (5
      50% by mass) were incorporated into the backbone of the new polymers to allow
      tuning of particle surface properties for potentially enhanced aerosolization
      efficiency and to decrease particle clearance rates by phagocytosis in the deep
      lung. The preparation of large porous particles with these new polymers was
      systematically approached, utilizing central composite design, to develop
      improved particle physical properties for deep lung delivery. Microparticles
      containing model drugs were made with sizes suitable for deposition in various
      regions of the lung following inhalation as a dry powder. Due to such properties
      as surface erosion (leading to continuous drug release profiles), erosion times
      ranging from hours to days (allowing control over drug delivery duration), and
      ability to incorporate up to 50% PEG in their backbone, these new systems may
      also find application as "stealth" carriers for therapeutic compounds following
      intravenous injection.

PMID- 12219835
TI  - Contact guidance of Walker carcinosarcoma cells by the underlying normal
      fibroblasts is inhibited by RGD-containing synthetic peptides.
AB  - The metastatic spread of malignant neoplasms is associated with active migration
      of cancer cells. The migration of neoplastic cells during the metastatic process
      may be affected by various extracellular factors, including chemoattractants,
      haptotactic signals, electric fields, substrate anisotropy, and cell-to-cell
      contacts. We examined the effect of homotypic collisions and heterotypic
      interactions with normal human skin fibroblasts on the motile activity of Walker
      carcinosarcoma cells. It was found that Walker carcinosarcoma cells moving in a
      dense population neither show contact inhibition of movement when colliding with
      one another nor increase their motile activity as a result of contact stimulation
      of motility. On the other hand, when plated onto the surface of aligned
      fibroblasts, Walker carcinosarcoma cells migrated mainly along the long axes of
      underlying fibroblasts as a result of contact guidance. The directional character
      of movement (but not the speed of migration) of Walker carcinosarcoma cells on
      the surface of aligned fibroblasts was completely effaced by RGD-containing
      synthetic peptide at a concentration of 1 mg/ml but not by 5 microM verapamil
      (selective voltage-gated calcium channel inhibitor) or 10 microM gadolinium
      chloride (non-specific blocker of mechanosensitive ion channels). The suppression
      of directional character of migration of tumour cells by RGD-containing peptide
      was associated with the decrease in the amount of fibronectin macromolecules
      attached to fibroblasts. This suggests that alignment and anisotropic
      distribution of fibronectin macromolecules may be responsible for contact
      guidance of tumour cells moving on the surface of fibroblasts.

PMID- 12219836
TI  - Characterization of afferent and efferent galanin-containing nerve fibres in the
      porcine ovary.
AB  - Double-labelling immunofluorescence combined with retrograde tracing revealed
      three subpopulations of galanin-immunoreactive nerve fibres innervating the
      porcine ovary. The first group originated in ipsilateral dorsal root ganglia Th11
      L5 and exhibited colocalization with substance P-, but not with tyrosine
      hydroxylase- or dopamine-beta-hydroxylase-immunoreactivity. These fibres supplied
      primordial follicles and large arteries of the ovarian hilus. The second group,
      arising from the sympathetic inferior mesenteric ganglion, was galanin
      immunoreactive, but non-reactive to substance P-, dopamine-beta-hydroxylase- or
      tyrosine-hydroxylase-antisera. Fibres of this type were sparsely distributed in
      the ovarian cortex. They were observed in connection with small cortical
      arterioles or in the ovarian cortical stroma. The third group of galanin
      containing nerve terminals originated from postganglionic neurons located in
      sympathetic chain ganglia Th15-L3 and S1. Most of them contained tyrosine
      hydroxylase- and dopamine-beta-hydroxylase-immunoreactivity. This subset of
      galanin-positive nerve fibres was the least frequent and was almost exclusively
      associated with cortical arterioles. The findings are indicative of an
      involvement of galanin in autonomic and sensory neuronal functions in the
      ovaries, possibly control of follicle maturation and blood flow.

PMID- 12219837
TI  - ENOS, ET-1 and ETB-R immunoreactivities in the porcine mesometrial lymphatics
      during the estrous cycle.
AB  - Abstract: Immunohistochemical localization and distribution of nitric oxide
      synthase (eNOS), endothelin (ET-1) and endothelin beta receptor (ETB-R) were
      investigated in precollector and collector lymph vessels in the broad ligament of
      the uterus during different phases of the estrous cycle in pigs. The polyclonal
      antibody for ET-1 and ETB-R and monoclonal antibody for eNOS isoform were used to
      perform observations on the light microscopic level. Immunoreactivities to ET-1,
      ETB-R and eNOS were observed in the endothelium of precollector and collector
      lymphangions but not in smooth muscle cells of the lymphatics examined. The
      staining for eNOS in the endothelial cells of all studied lymphatic vessels was
      stronger comparing to ET-1 and ETB-R. During the estrous cycle, only eNOS showed
      the correlation with the particular phases of the estrous cycle. The differences
      between ET-1 and ETB-R immunoreactivities were very slight and rather independent
      of the size or type of the lymphatic lymphangions and estrous cycle. The highest
      immunoreactivity level for eNOS was displayed by collector lymphangions with
      widened lumen in the follicular phase comparing to the precollector ones. During
      the luteal phase, a slight decrease in the reaction intensity was observed. The
      immunoreactivities for ET-1 in the endothelium of the studied vessels was not
      comparable with the presence or with the reactivity level of ETB-R. Optically
      stronger immunoreaction for ETB-R was observed in the cytoplasm of collector
      lymphangions in the follicular phase. eNOS, ET-1 and ETB-R were also present in
      the cytoplasm of the lymphatic valves. These results suggest that ET-1 and eNOS
      can play a role in the mechanisms regulating the vascular contractile activity,
      promoting lymph flow during the estrous cycle in the porcine broad ligament.

PMID- 12219838
TI  - Influence of the sagittal advancement of mandibulae on myofibrillar ATPase
      activity and myosin heavy chain content in the masticatory muscles of pigs.
AB  - Endurance muscle stress leads to polymorphic expression of myosin heavy chains
      (MyHC). Histochemical and electrophoretic analyses were performed on different
      masticatory muscles (masseter, temporal, geniohyoid and medial pterygoid) of 10
      weeks old pigs after 28 days of chronic sagittal advancement of the mandibulae.
      The differentiation between fiber types was investigated histochemically with the
      myofibrillar ATPase (mATPase) method and by immunohistochemistry. Expression of
      different MyHC isoforms was also assessed by means of immunoblotting with
      monoclonal antibodies. The results of both methods were compared. Chronic
      sagittal advancement of the mandibulae led to an increase in the cross-sectional
      area of type I fibers and type I MyHC in the anterior part of the masseter, the
      distal part of the temporal and the medial pterygoid muscle. In the present
      study, clear differentiation between type I and type II muscle fibers in all
      histological analyses was possible. However, mATPase classification of subtypes
      of type II fibers may lead to misinterpretations. Additionally, a direct
      correlation between the type I MyHC concentration and the type I fibers was seen
      in enzyme histochemical and immunohistochemical staining. The defined cross
      section of fibers is important for the histological investigation in small
      muscles. The immunoblot method seems to be more sensitive and less subjective for
      measurement of muscle changes. It can be concluded that the immunoblot method
      used for measuring the MyHC content is a valid alternative for fiber typing in
      small muscles as it is less time-consuming and more sensitive than qualitative
      histochemistry.

PMID- 12219839
TI  - Effect of exogenous pulmonary surfactant preparations on the structure of
      pulmonary alveoli in newborn rats.
AB  - Treatment of pre-term newborns with exogenous surfactant preparation is a well
      established part of the therapy for respiratory distress syndrome of the newborns
      (RDS). Since the introduction of surfactant into clinical practice in 1980,
      hundreds of studies have been published describing beneficial effects of such
      treatment. There is only limited number of morphological publications reporting
      adverse effects of surfactant administration. The aim of the present study is to
      describe morphological changes in the lung after surfactant administration to
      healthy newborn rats. Two types of surfactant were used: Exosurf (Glaxo Wellcome,
      England) and Survanta (Abbott Laboratories, USA). Surfactant preparation were
      given intratracheally in single dose (bolus) (100 mg of lipids per kg b.w.).
      Animals from control group received 0.9% saline in equivalent volume. Lung
      specimens were taken 15, 20, 25 and 30 minutes after drug administration and
      evaluated by light and electron microscopy. There was no damage in lungs from the
      control group. Tissue specimens from the Exosurf group revealed severe
      pathological changes: foci of atelectasis, frank edema in the parenchyma, focal
      disruption of air-blood barrier, hemorrhages in many alveoli, surfactant
      particles in many alveolar capillaries, and strongly activated alveolar
      macrophages. In this group changes appeared as early as 15 min after surfactant
      administration and intensity of lung injury increased with time. Also, Survanta
      administration caused damage to the lung tissue. However, the changes were less
      intense and appeared later (20-25 minutes after Survanta treatment). In
      conclusion, the presented morphological findings proved that exogenous surfactant
      administration to healthy rat newborns caused lung damage. Comparing two
      different surfactant preparation, Exosurf and Survanta, it was shown that the
      former one produced stronger and faster damage to lung alveoli than the latter
      one.

PMID- 12219840
TI  - Comparison of the cell immunophenotype of metastatic and primary foci in stage IV
      S neuroblastoma.
AB  - Neuroblastoma represents one of the most frequently developing malignant solid
      tumours in children. At the time of diagnosis, in more than half of the cases,
      metastatic cells are also present in the bone marrow. The present study was aimed
      at immunocytochemical analysis of selected neuropeptide manifestation in
      metastatic cells of neuroblastoma in bone marrow and at comparing the obtained
      results with the immunophenotype of parental neuroblastoma cells. The studies
      were performed on bone marrow material obtained from children treated at the
      Department of Paediatric Haematology and Oncology, University of Medical
      Sciences, Poznan, Poland, in 1998-2000. Immunocytochemical analysis of nervous
      tissue markers (employing the immunomax technique) involved 36 bone marrow
      preparations obtained from 27 children. The analysis included expression of
      neuron-specific enolase (NSE), PGP 9.5 protein, substance P (SP), chromogranin A
      (ChA), bombesin (B), galanin (G), neuropeptide Y (NPY) and vasoactive intestinal
      peptide (VIP). Close to 90% metastatic cells in bone marrow were found to exhibit
      NSE+SP+B+ phenotype and over a half of the cells manifested additionally
      expression of PGP 9.5+ChA+NPY+. Comparison of the obtained results with the
      immunophenotype of neuroblastoma cells obtained directly from the primary tumour
      demonstrated high correlation of NSE, SP and PGP 9.5 expression. Due to the
      relative ease of obtaining the bone marrow material and absence of neuromarkers
      in bone marrow metastatic cells in solid tumours other than neuroblastoma,
      determination of immunophenotype of the cells may represent a valuable
      supplementation in preliminary diagnosis of this tumour in children.

PMID- 12219841
TI  - Expression of class III beta-tubulin in neuroendocrine tumours of
      gastrointestinal tract.
AB  - Class III b-tubulin is presented as a specific marker for the cells of neuronal
      origin as well as for the tumours originating from these cells. Its expression is
      considered one of the earliest events that appear in the cells revealing neuronal
      differentiation. Using monoclonal antibody TU-20 in an immunohistochemical
      analysis, we studied the expression of class III b-tubulin in gastrointestinal
      carcinoid tumours. Paraffin-embedded, formalin-fixed tissue sections from 49
      tumour samples obtained from following locations: stomach (4 cases), small
      intestine (8 cases), appendix (18 cases), rectum (3 cases), pancreas (5 cases),
      liver metastases (7 cases) and lymph node metastases (4 cases) were used in the
      study. In 41 of the 49 tumour samples (83.7%), positive staining for class III b
      tubulin was detected, while 8 tumour samples (16.3%) were negative. Expression of
      class III b-tubulin was prominent in all three rectal carcinoids and in three
      atypical carcinoids located in small intestine. Pancreatic neuroendocrine tumours
      revealed either weak immunostaining (2 cases), or were negative for this marker
      (3 cases). The intensity of class III b-tubulin immunolabelling was not related
      to the degree of tumour differentiation. The results of this study suggest that
      class III b-tubulin could be a perspective marker for gastrointestinal
      neuroendocrine tumours. Moreover, the differences in its expression could also
      elucidate some aspects of histogenetic relationships of neuroendocrine tumours of
      gastrointestinal tract.

PMID- 12219842
TI  - Egg yolk platelet proteins from Xenopus laevis are amyloidogenic.
AB  - The association of amphibian (Xenopus laevis) egg yolk platelet proteins,
      represented predominantly by lipovitellin, was studied as a model of the
      formation of amyloid deposits. Two kinds of molecular organization formed by this
      protein material - native and heat-denatured - were found to exhibit amyloid
      properties although they differ significantly in structural organization. The
      first consisted in protein molecules arranged in the natural, physiological, net
      like platelet organization, with a tendency to orient uni-directionally. The
      second was obtained by the gradual removal of Congo red from lipovitellin
      denatured by heating in an excess of dye. This procedure produced the twisted
      fibrillar organization of molecules typical for amyloids, represented
      predominantly by end-to-end associated major polypeptide chains of lipovitellin.
      Both native and denatured structural forms bind Congo red and produce a green
      birefringence effect, confirming the near parallel alignment of the complexed
      Congo red molecules. However, a dye(1,4-bis(1-amino-4-sulfonaphtyl-2
      azo)phenylene) closely related to Congo red but with a very weak self-assembling
      tendency appeared inactive when the spectral shift was studied in a cross
      polarization system, indicating in this way that dye supramolecularity is an
      extra factor which may determine binding to amyloid proteins and specific
      spectral effects.

PMID- 12219843
TI  - Combinatorial labelling of DNA probes enables multicolour fluorescence in situ
      hybridisation in plants.
AB  - This paper demonstrates a simple but effective use of combinatorial probes to
      label plant chromosomes by multicolour fluorescence in situ hybridisation (FISH).
      Three different DNA probes were labelled with only two different fluorophores,
      hybridised to somatic metaphase chromosomes of Secale cereale and Triticum
      aestivum, simultaneously visualised, and unequivocally distinguished in a single
      FISH experiment. Combinatorial labelling can augment karyotypical investigations,
      physical mapping of chromosomes and other analyses in plants based upon FISH.

PMID- 12219844
TI  - Different DNA methylation pattern in A and B chromosomes of Crepis capillaris
      detected by in situ nick-translation. Comparison with molecular methods.
AB  - Experiments were performed on Crepis capillaris callus lines with 0, 1 and 2 B
      chromosomes and on hairy root lines without or with 1 and 2 B chromosomes.
      Comparison of HPLC results for DNA from calli differing in number of B
      chromosomes did not reveal any significant differences in methylation level (30.4
      +/- 1.1%, 30.9 +/- 1.2%, 31.7 +/- 1.7% in lines without or with one or two B
      chromosomes respectively) which could be attributed to the number of B
      chromosomes. Restriction patterns obtained after DNA digestion with HhaI, HpaII,
      MspI or HaeIII (i.e. restriction enzymes sensitive to cytosine methylation) were
      similar in calli and apical root segments and also did not depend on the presence
      or number of B chromosomes. Methylation of B chromosomes higher than that of A
      chromosomes was demonstrated by fluorescent in situ nick translation driven by
      HpaII, MspI or HaeIII in metaphase chromosomes. After short digestion (I and 3
      h), B chromosomes, in contrast to A chromosomes, were weakly labelled or not
      labelled at all, which indicates longer distances between target sequences
      containing unmethylated cytosine in the former.

PMID- 12219845
TI  - Radiobiological indices that consider volume: a review.
AB  - Understanding and predicting the impact of any radiotherapy treatment is critical
      if patients are to receive treatment with a high likelihood of eliminating the
      tumour and low likelihood of complications. One of the major contributing factors
      in determining these effects is the volume treated. This review assesses the
      current use and accuracy of a series of models which consider volume, building on
      a previous review which investigated the impact of fractionation particularly
      with respect to the linear quadratic model. Volume is particularly important in
      assessing the overall effect with respect to destroying the clonogenic cells and
      preventing damage to the normal tissues. Dose volume histograms are one of the
      simplest and most useful forms of representing volume information, however it is
      difficult to correlate plans based only on DVHs. For this reason various
      reduction schemes have been introduced and tumour control probability and normal
      tissues complication probability models adjusted to use this information. Many of
      these models have proved quite useful in the clinic although they are limited by
      the available radiobiological data.

PMID- 12219846
TI  - Assessment of flatness and symmetry of megavoltage x-ray beam with an electronic
      portal imaging device (EPID).
AB  - The input/output characteristics of the Wellhofer BIS 710 electronic portal
      imaging device (EPID) have been investigated to establish its efficacy for
      periodic quality assurance (QA) applications. Calibration curves have been
      determined for the energy fluence incident on the detector versus the pixel
      values. The effect of the charge coupled device (CCD) camera sampling time and
      beam parameters (such as beam field size, dose rate, photon energy) on the
      calibration have been investigated for a region of interest (ROI) around the
      central beam axis. The results demonstrate that the pixel output is a linear
      function of the incident exposure, as expected for a video-based electronic
      portal imaging system. The field size effects of the BIS 710 are similar to that
      of an ion chamber for smaller field sizes up to 10 x 10 cm2. However, for larger
      field sizes the pixel value increases more rapidly. Furthermore, the system is
      slightly sensitive to dose rate and is also energy dependent The BIS 710 has been
      used in the current study to develop a QA procedure for measurements of flatness
      and symmetry of a linac x-ray beam. As a two-dimensional image of the radiation
      field is obtained from a single exposure of the BIS 710, a technique has been
      developed to calculate flatness and symmetry from a defined radiation area. The
      flatness and symmetry values obtained are different from those calculated
      conventionally from major axes only (inplane, crossplane). This demonstrates that
      the technique can pick up the "cold" and "hot" spots in the analysed area,
      providing thus more information about the radiation beam. When calibrated against
      the water tank measurements, the BIS 710 can be used as a secondary device to
      monitor the x-ray beam flatness and symmetry.

PMID- 12219847
TI  - Display of positron emission tomography with Cadplan.
AB  - Recent clinical experience at Peter MacCallum Cancer Institute (PMCI) with the
      use of unregistered Positron Emission Tomography (PET) images for radiotherapy
      target marking in the lung suggests that co-registered PET images would be
      invaluable. PMCI has three radiotherapy treatment planning systems but none of
      them currently is able to display or co-register PET images with Computed
      Tomography (CT) images. This paper details the approach taken to display co
      registered PET images with the CADPLAN treatment planning system. CT Image files
      are normally transferred to Cadplan by DICOM transfer, but the Cadplan DICOM
      server will not receive (has no presentation context for) PET images. The
      fundamental design of the CADPLAN system envisages display of only a single image
      dataset, which must be a CT scan for planning reasons. The problem of data
      transfer is crudely solved by File Transfer Protocol (FTP) over the network.
      Fortunately the multislice format of the PET image files makes individual
      transfer manageable. A menu based C program running at the same time as Cadplan
      is invoked to sample the DICOM PET Image and create multiple Cadplan CART image
      format files that are co-registered with each existing transverse CT slice. With
      the Cadplan in contour mode, the program allows the co-registered PET images to
      be swapped in and out of the image section of the CART files promptly, while
      keeping the contour information. This allows radiotherapy target volumes to be
      marked using transverse PET emission images, and effectively circumvents the
      design constraints prohibiting the display of more than one image set. Contours
      can be over-laid for review on reconstructed sagittal or coronal views of CT or
      PET images constructed using the standard Cadplan tools. Co-registration is
      facilitated by identical positioning with the aid of lasers and FDG loaded
      fiducial markers on the PET scanner and CT couch. A polyurethane cast fixed with
      EFFILOCK is used to ensure identical patient orientation on the CT and PET
      couches. Since both imaging modalities are without significant geometric
      distortion the co-registration is then simply a translation. PET transmission
      images can be used for co-registration verification. The practical implementation
      of display of PET images with CADPLAN has enabled us to begin a trial of 10
      patients, the results of which will be reported separately.

PMID- 12219848
TI  - Verification of CT number to density conversion for a simulator-T attachment.
AB  - The calculation and verification of a CT number to density conversion table for a
      simulator-CT attachment known as Scanvision, which provides CT images for
      radiotherapy treatment planning, is presented. While the linear fit for CT-number
      to-density is similar to most conventional doughnut gantry CT scanners, an offset
      of approximately 178 Hounsfield units was found for air using a polyethylene
      normalisation, and approximately 262 for air using air normalisation. The offset
      continues for other low-density samples. Results show that the simulator-CT
      reproducibly measures CT numbers. However a separate calibration line needs to be
      entered into the radiotherapy planning computer to ensure accurate CT-number-to
      density. conversion.

PMID- 12219849
TI  - Image enhancement for electronic visual prostheses.
AB  - This paper briefly describes the framework of artificial human vision systems and
      identifies several image processing techniques which could enhance the
      information content of artificially-induced images. We describe our own research
      in this area, which aims to assess the performance of proposed devices,
      specifically the usefulness of low quality images associated with electronic
      visual prostheses. Our subjective assessment studies using representative test
      patterns have investigated how much information and what types of information are
      needed to recognise or perceive a scene. 174 normally sighted subjects viewed a
      set of low quality (low spatial resolution and low grey-scale) static images.
      Results from this testing has identified informative image processing operations
      which lead to improved understanding of picture content.

PMID- 12219850
TI  - Meritocracy and opposition to affirmative action: making concessions in the face
      of discrimination.
AB  - Typically, people who strongly endorse the merit principle and believe that
      outcomes should be given to those most deserving oppose affirmative action (AA)
      programs that violate this principle. However, how do they respond to AA when
      faced with a great deal of workplace discrimination? The authors hypothesized
      that people who care strongly about merit should be motivated to combat
      discrimination because it biases the assessment of merit. Consequently, these
      individuals should make concessions for AA. The authors found support for their
      hypothesis when investigating (a) participants' preexisting perceptions of
      workplace discrimination and (b) experimentally induced perceptions of
      discrimination. They discuss the implications of these results for the psychology
      of meritocracy and for resistance to AA.

PMID- 12219851
TI  - Walking the tightrope between feeling good and being accurate: mood as a resource
      in processing persuasive messages.
AB  - Three studies investigated the influence of mood states on the processing of
      positive and negative information regarding caffeine consumption and on the
      impact of this information on one's mood, attitudes, and intentions. The results
      were consistent with the predictions of the mood-as-a-resource hypothesis: First,
      the induction of positive mood in high (compared with low) caffeine consumers
      enhanced recall of negative information about caffeine consumption. Second,
      processing information about caffeine consumption undermined the positive mood of
      high (but not low) caffeine consumers. Third, the induction of positive mood
      enhanced the impact of negative information about caffeine on high (compared with
      low) caffeine consumers' attitudes and intentions toward caffeine consumption.

PMID- 12219852
TI  - Dispelling the illusion of invulnerability: the motivations and mechanisms of
      resistance to persuasion.
AB  - Three studies examined the impact of a treatment designed to instill resistance
      to deceptive persuasive messages. Study 1 demonstrated that after the resistance
      treatment, ads using illegitimate authority-based appeals became less persuasive,
      and ads using legitimate appeals became more persuasive. In Study 2, this
      resistance generalized to novel exemplars, persevered over time, and appeared
      outside of the laboratory context. In Study 3, a procedure that dispelled
      participants' illusions of invulnerability to deceptive persuasion maximized
      resistance to such persuasion. Overall, the present studies demonstrate that
      attempts to confer resistance to appeals will likely be successful to the extent
      that they install 2 conceptual features: perceived undue manipulative intent of
      the source of the appeal and perceived personal vulnerability to such
      manipulation.

PMID- 12219853
TI  - Assimilative behavior identification can also be resource dependent: the unimodel
      perspective on personal-attribution phases.
AB  - Three studies examine the role of situational constraint information on behavior
      identification. It was found that where the behavior-identification task is
      relatively easy assimilation of the behavior-identification to situational
      constraints is independent of cognitive load. However, where the behavior
      identification task is relatively difficult, assimilation is undermined by load.
      Given that the discounting of situational constraint information, too, can be
      independent of load where the dispositional-inference task is easy, and is load
      dependent when the task is difficult, it appears that both assimilation and
      discounting behave identically in regard to load. This conclusion is consistent
      with the judgmental unimodel whereby behavior identification and dispositional
      inference differ in the contents of the judgmental questions they address while
      sharing the underlying process whereby these questions are answered.

PMID- 12219854
TI  - When rejection stings: how self-esteem constrains relationship-enhancement
      processes.
AB  - Three experiments examined how needs for acceptance might constrain low versus
      high self-esteem people's capacity to protect their relationships in the face of
      difficulties. The authors led participants to believe that their partner
      perceived a problem in their relationship. They then measured perceptions of the
      partner's acceptance, partner enhancement, and closeness. Low but not high self
      esteem participants read too much into problems, seeing them as a sign that their
      partner's affections and commitment might be waning. They then derogated their
      partner and reduced closeness. Being less sensitive to rejection, however, high
      self-esteem participants affirmed their partner in the face of threat.
      Ironically, chronic needs for acceptance may result in low self-esteem people
      seeing signs of rejection where none exist, needlessly weakening attachments.

PMID- 12219855
TI  - The "I," the "we," and the "when": a meta-analysis of motivational primacy in
      self-definition.
AB  - What is the primary motivational basis of self-definition? The authors meta
      analytically assessed 3 hypotheses: (a) The individual self is motivationally
      primary, (b) the collective self is motivationally primary, and (c) neither self
      is inherently primary; instead, motivational primacy depends on which self
      becomes accessible through contextual features. Results identified the individual
      self as the primary motivational basis of self-definition. People react more
      strongly to threat and enhancement of the individual than the collective self.
      Additionally, people more readily deny threatening information and more readily
      accept enhancing information when it pertains to the individual rather than the
      collective self, regardless of contextual influences. The individual self is the
      psychological home base, a stable system that can react flexibly to contextual
      influences.

PMID- 12219856
TI  - Accountability as a deterrent to self-enhancement: the search for mechanisms.
AB  - Although self-enhancement is linked to psychological benefits, it is also
      associated with personal and interpersonal liabilities (e.g., excessive risk
      taking, social exclusion). Hence, structuring social situations that prompt
      people to keep their self-enhancing beliefs in check can confer personal and
      interpersonal advantages. The authors examined whether accountability can serve
      this purpose. Accountability was defined as the expectation to explain, justify,
      and defend one's self-evaluations (grades on an essay) to another person
      ("audience"). Experiment 1 showed that accountability curtails self-enhancement.
      Experiment 2 ruled out audience concreteness and status as explanations for this
      effect. Experiment 3 demonstrated that accountability-induced self-enhancement
      reduction is due to identifiability. Experiment 4 documented that identifiability
      decreases self-enhancement because of evaluation expectancy and an accompanying
      focus on one's weaknesses.

PMID- 12219857
TI  - Social exclusion causes self-defeating behavior.
AB  - Four experiments tested the idea that social exclusion leads to (unintentionally)
      self-defeating behavior. Exclusion was manipulated by telling some people that
      they were likely to end up alone later in life. This randomly assigned feedback
      caused people to take irrational, self-defeating risks (Experiments 1 and 2),
      choose unhealthy, rather than healthy, behaviors (Experiment 3), and
      procrastinate longer with pleasurable activities rather than practicing for an
      upcoming test (Experiment 4). A control group, who heard that their future would
      be marred by frequent accidents, did not show these self-defeating patterns.
      Thus, the effect goes beyond just hearing bad news. Emotional distress did not
      significantly mediate these effects across 3 different mood measures.

PMID- 12219858
TI  - "Me versus just us versus us all" categorization and cooperation in nested social
      dilemmas.
AB  - In its generic form, a social dilemma poses a conflict between private and
      collective interests. People are often faced, however, with a conflict between
      private, (sub)group, and collective interests. This study examines participants'
      simultaneous weighing of these 3 nested interests. The results show that
      increasing the salience of social categorization of any level of the hierarchy
      (i.e., 6 individuals, 2 subgroups. 1 collective) increases participants' concern
      for and contributions to the corresponding level of interest (Experiment 1). One
      can promote concern for and contributions to the collective interest, which are
      lowest under categorization as 2 subgroups, by individuating the members of the
      individuals' own subgroup and/or the opposing subgroup (Experiment 2) and by
      cross-categorization with the opposing subgroup (Experiment 3).

PMID- 12219859
TI  - Stereotype performance boosts: the impact of self-relevance and the manner of
      stereotype activation.
AB  - The activation of positive stereotypes has been shown to produce academic
      performance boosts. Evidence regarding the role of self-relevance in producing
      such effects has been mixed. The authors propose that the subtlety of stereotype
      activation plays a key role in creating performance boosts among targets and
      nontargets of stereotypes. Study 1 found that subtle stereotype activation
      boosted performance in targets, but blatant activation did not. Study 2 was
      conducted on both targets and nontargets using different methods of stereotype
      activation. Again, targets showed performance boosts when stereotypes were subtly
      activated but not when they were blatantly activated. Nontargets, however, showed
      boosts in performance only when stereotypes were blatantly activated. The role of
      self-relevance in mediating sensitivity to stimuli is discussed.

PMID- 12219860
TI  - When similarity breeds content: need for closure and the allure of homogeneous
      and self-resembling groups.
AB  - Four studies explored the relation between members' need for cognitive closure
      and their feelings toward groups. It was found that high (vs. low) need for
      closure individuals liked in-groups and out-groups more as function of the degree
      to which their membership was perceived as homogeneous (Studies 1-4), provided it
      was also self-similar (Studies 3 and 4). These results are discussed in terms of
      the relation between need for closure and homogeneous (vs. heterogeneous) groups'
      apparent potential as "closure providers."

PMID- 12219861
TI  - The epistemic benefits of trait-consistent mood states: an analysis of
      extraversion and mood.
AB  - One must consider both trait and state affect to predict individual differences
      in emotional processing. The present results document a novel trait-state
      interaction that is consistent with proposals concerning the epistemic functions
      of affect (A. R. Damasio, 1994). Four studies tested the effects of extraversion
      and mood on motivation-relevant processing. Study 1 measured naturally occurring
      mood, whereas Studies 2-4 manipulated mood. Extraverts were faster to link events
      to their personal motivations when in a positive mood state, whereas introverts
      were faster to do so in a neutral or negative mood state. Further findings
      indicate that this interaction affects attitude accessibility rather than event
      elaboration. Overall, the authors suggest that there are pragmatic benefits to
      trait-consistent moods, particularly for processing motivation-relevant stimuli.

PMID- 12219862
TI  - The dynamics of threat and challenge appraisals prior to stressful achievement
      events.
AB  - Research on cognitive appraisal of stressful achievement events has emphasized
      threat appraisals and anxiety. The present research also focused on challenge and
      positive emotion. Study 1 used hypothetical scenarios of stressful events. Study
      2 explored temporal pattems of appraisal and emotion prior to an exam. Compared
      with threat appraisals, trait and state challenge appraisals were associated with
      more confident coping expectancies, lower perceptions of threat, higher positive
      emotion, and more beneficial perceptions of the effects of appraisal and emotion
      on performance. Beneficial perceptions of state appraisals were associated with
      higher exam performance. These findings were interpreted in the context of
      theoretical perspectives on the cognitive appraisal of stressful events and the
      adaptive functions of challenge and positive emotion.

PMID- 12219863
TI  - Are measures of self-esteem, neuroticism, locus of control, and generalized self
      efficacy indicators of a common core construct?
AB  - The authors present results of 4 studies that seek to determine the discriminant
      and incremental validity of the 3 most widely studied traits in psychology-self
      esteem, neuroticism, and locus of control-along with a 4th, closely related trait
      generalized self-efficacy. Meta-analytic results indicated that measures of the 4
      traits were strongly related. Results also demonstrated that a single factor
      explained the relationships among measures of the 4 traits. The 4 trait measures
      display relatively poor discriminant validity, and each accounted for little
      incremental variance in predicting external criteria relative to the higher order
      construct. In light of these results, the authors suggest that measures
      purporting to assess self-esteem, locus of control, neuroticism, and generalized
      self-efficacy may be markers of the same higher order concept.

PMID- 12219864
TI  - Self-esteem and persistence in the face of failure.
AB  - In 2 studies, the authors examined self-esteem, persistence, and rumination in
      the face of failure. Study 1 manipulated degree of failure and availability of
      goal alternatives. When an alternative was available, high self-esteem (HSE)
      participants persisted more than low self-esteem (LSE) participants after a
      single failure, but less after repeated failure. When no alternative was
      available, no self-esteem differences in persistence emerged. LSE participants
      ruminated more than HSE participants. Study 2 examined persistence and rumination
      for 10 personal goals across an academic year. HSE participants were better
      calibrated (higher within-subject correlations between perceived progress and
      persistence across goals), had higher overall levels of persistence, higher grade
      point averages, and lower levels of rumination than LSE participants. Although
      traditional views that emphasize the tenacious persistence of HSE individuals
      need revision, HSE people appear more effective in self-regulating goal-directed
      behavior.

PMID- 12219865
TI  - Wanting, having, and satisfaction: examining the role of desire discrepancies in
      satisfaction with income.
AB  - In 3 studies, the authors tested the predictors of income satisfaction, examining
      whether discrepanc between the things people have and the things they desire
      predict satisfaction. Study 1 manipulated the desirability of items that can be
      purchased with participants' income, and showed that their satisfaction with that
      income depended on the desirability of these items. Study 2 demonstrated that
      whether people's income enabled them to purchase the things they desired
      influenced their satisfaction with income. Study 3 found that the effect of
      comparisons with a person's past on income satisfaction is completely mediated by
      one's desires; and the effect of social comparison on income satisfaction is
      partially mediated by desires. Thus, desires play a pivotal role in determining
      people's satisfaction with income.

PMID- 12219866
TI  - Influence of long-term racial environmental composition on subjective well-being
      in African Americans.
AB  - Two studies (N = 126, N = 114) of African Americans supported a model predicting
      that more racially segregated life contexts are associated with feelings of
      acceptance by other in-group members and, to a lesser extent, rejection by out
      group members. In-group acceptance and out-group rejection in turn influenced
      identification with the in-group, which was a strong predictor of psychological
      well-being. Alternative models were not supported. Results suggest that
      environments that are segregated offer in-group support and acceptance, thereby
      protecting self-esteem against possible perils of rejection by a powerful out
      group. Findings suggest that the improvement of intergroup relations should not
      be at the expense of intragroup relations.

PMID- 12219867
TI  - Personality change over 40 years of adulthood: hierarchical linear modeling
      analyses of two longitudinal samples.
AB  - Normative personality change over 40 years was shown in 2 longitudinal cohorts
      with hierarchical linear modeling of California Psychological Inventory data
      obtained at multiple times between ages 21-75. Although themes of change and the
      paucity of differences attributable to gender and cohort largely supported
      findings of multiethnic cross-sectional samples, the authors also found much
      quadratic change and much individual variability. The form of quadratic change
      supported predictions about the influence of period of life and social climate as
      factors in change over the adult years: Scores on Dominance and Independence
      peaked in the middle age of both cohorts, and scores on Responsibility were
      lowest during peak years of the culture of individualism. The idea that
      personality change is most pronounced before age 30 and then reaches a plateau
      received no support.

PMID- 12219868
TI  - Personality and happiness: a national-level analysis.
AB  - The possibility that national personality traits could explain national
      subjective well-being (SWB) is controversial, with many researchers arguing that
      traits are irrelevant to any national-level analysis. The weaknesses of this
      standpoint are reviewed, followed by a series of empirical investigations. Using
      Eysenck's 3-factor model (H. J. Eysenck & S. B. G. Eysenck, 1975) and P. T. Costa
      and R. M. McCrae's (1992b) 5-factor model, the authors found that Neuroticism and
      Extraversion correlated significantly with national SWB. Lie scale scores were
      also related strongly to national SWB. Neuroticism and Extraversion incrementally
      predicted SWB above gross national product per capita. The strength of these
      results indicates that personality can have stronger relationships at national
      levels of analysis than at the individual level. National personality traits
      appear to be unwisely neglected, having considerable but largely unconsidered
      explanatory power.

PMID- 12219869
TI  - Transforming growth factor-beta1 levels in hypertensive patients: association
      with body mass index and leptin.
AB  - BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) has been demonstrated to
      be overexpressed in hypertension. Leptin, an adipocyte product, has been shown to
      play a role in obesity-related hypertension and in vitro studies demonstrated a
      biologic interaction between leptin and TGF-beta1. Thus, we evaluate a possible
      in vivo association between TGF-beta1, body mass index (BMI), and leptin
      circulating levels in hypertensive subjects. METHODS: Blood samples for fasting
      leptin and TGF-beta1, were evaluated in 29 overweight, 46 obese, and 29 nonobese
      hypertensive patients before and after a 12-week calorie-restricted diet.
      Monocyte cultures were used for in vitro experiments. RESULTS: Transforming
      growth factor-beta1 was significantly elevated in hypertensive obese patients (n
      = 46) as compared with TGF-beta1 levels of hypertensive patients with normal BMI
      (n = 29) (8. 9 +/- 3 ng/mL v 4.4 +/- 2; P < .001). The circulating levels of TGF
      beta1 were associated with BMI and leptin levels in an univariate analysis (r =
      0.59, P < .0001; r = 0.62, P < .0001, respectively) and these associations were
      still present after stepwise multivariate analysis. Weight loss of 10% produced a
      parallel decrease in TGF-beta1 (from 8.9 +/- 3 ng/mL to 5.3 +/- 2.8 ng/mL; P <
      .01) and leptin levels (from 30 +/- 24 ng/mL to 17 +/- 14; P < .05). In vitro
      experiments showed that leptin is able to induce a dose-dependent increase in TGF
      beta1 production and mRNA expression in human monocyte cultures. CONCLUSIONS: Our
      data indicate that TGF-beta1 levels are positively associated with BMI and leptin
      levels in hypertensive patients and suggest that adipose tissue may be an
      important determinant of TGF-beta1 levels possibly by a leptin-dependent pathway.

PMID- 12219870
TI  - Positive association between circulating free insulin-like growth factor-1 levels
      and coronary flow reserve in arterial systemic hypertension.
AB  - BACKGROUND: The reduction of coronary flow reserve (CFR) found in arterial
      hypertension may be due to changes in afterload, left ventricular (LV) structure,
      and metabolic factors. Also, insulin-like growth factor-1 (IGF-1) may be
      associated with the magnitude of CFR in relation to its modulating action on
      cardiac and endothelial function. METHODS: A total of 44 newly diagnosed,
      untreated hypertensive patients, who were free of diabetes mellitus and coronary
      artery disease, underwent M-mode analysis, second-harmonic Doppler
      echocardiographic assessment of CFR (dipyridamole infusion 0.56 mg/kg
      intravenously in four patients), determination of circulating free IGF-1, and
      insulin resistance. Based on CFR levels, hypertensive subjects were divided into
      two groups: 18 with normal CFR (> or = 2) and 26 with impaired CFR (<2). RESULTS:
      Patients with normal CFR had lower diastolic blood pressure, heart rate, and LV
      mass index but higher free circulating IGF-I than patients with reduced CFR (P <
      .001). Insulin resistance was not significantly different between the two groups.
      In a first multilinear regression analysis that included demographic and
      echocardiographic variables, insulin resistance was independently associated with
      CFR (standardized beta coefficient = -0.31, P < .05) in the overall population.
      However, in a subsequent model which included also IGF-1, the relationship
      between insulin resistance and CFR disappeared, whereas IGF-1 was the main
      independent determinant of CFR (beta = 0.51, P < .0002). CONCLUSIONS: Free IGF-1
      circulating levels are independently associated with CFR in hypertensive
      individuals free of overt coronary artery disease. A possible beneficial effect
      exerted by IGF-1 on coronary blood flow may be supposed in arterial hypertension.

PMID- 12219871
TI  - Excess dietary glucose alters renal function before increasing arterial pressure
      and inducing insulin resistance.
AB  - BACKGROUND: Diets high in carbohydrates are associated with hypertension,
      activation of the renin-angiotensin system, hyperinsulinemia, insulin resistance,
      and renal dysfunction. This study tests the hypothesis that the initial effect of
      a long-term high carbohydrate diet is a renin-angiotensin system dependant
      impairment of renal function. METHODS: Three-week-old male Sprague-Dawley rats
      drank water containing 5% glucose or water alone. Four weeks later, arterial
      pressure was continuously recorded in conscious restrained rats. Urine and blood
      samples were collected by catheter before, during, and after intravenous saline
      infusion, and fasting glucose tolerance tests were performed to estimate insulin
      resistance. To assess the possible role of the renin-angiotensin system, a group
      of glucose-fed rats was treated with oral captopril for 2 days before the renal
      function study. RESULTS: Despite slightly and significantly lowered body weight,
      the treatments did not significantly alter heart and kidney weights, arterial
      pressure, or heart rate. Non-fasting blood sugar levels were slightly higher in
      the two groups of glucose-fed rats compared with the control rats (P < .05), but
      fasting blood sugar concentration and glucose tolerance were not significantly
      different among groups. The glucose-fed rats displayed significantly impaired
      renal diuresis and natriuresis as well as significantly elevated glomerular
      filtration rate and filtration fraction, but administration of captopril
      corrected these impairments. Effective renal blood flow and renal vascular
      resistance were not significantly different among groups. CONCLUSIONS: These
      results indicate that diets high in carbohydrates impair renal function before
      they increase arterial pressure, and that this effect is dependent on an intact
      renin-angiotensin system.

PMID- 12219872
TI  - The relationship of waist circumference to blood pressure: the Olivetti Heart
      Study.
AB  - BACKGROUND: The association between overweight, high blood pressure (BP), and
      insulin resistance is well established, but the role of body fat distribution in
      this association has yet to be fully elucidated. The aim of this study was to
      investigate the role of central adiposity in the association between overweight,
      high BP, and insulin resistance. METHODS: A total of 1,079 men participated in
      the follow-up of the Olivetti Heart Study from 1994 to 1995. The present analysis
      includes 768 men, after the exclusion of 184 participants on pharmacological
      treatment for hypertension. In 65 men fasting blood glucose was >7 mmol/L; in 48,
      age was below or above 2 standard deviations from the mean of the population; and
      in 14 the data set was incomplete. Anthropometric indices of adiposity, metabolic
      variables (including fasting serum insulin and homeostasis model assessment
      [HOMA] index of insulin sensitivity), and BP were measured. RESULTS: In
      univariate analysis, waist circumference was the anthropometric index that best
      correlated with BP (P < .001). In multiple regression analysis, waist
      circumference remained the strongest independent predictor of BP after adjustment
      for confounders. Significant increase of systolic (P value for trend analysis <
      .001) and diastolic (P < .001) pressure, heart rate (P = .003), fasting and
      postload serum insulin (P < .001), and HOMA index of insulin sensitivity (P <
      .001) were observed across age-adjusted quintiles of waist circumference. Greater
      degrees of central adiposity were associated with higher prevalence of elevated
      BP values and insulin resistance (P value < .001, chi2 for linear trend).
      CONCLUSIONS: In middle-aged men, a central distribution of body fat is associated
      with increased BP, independently of body mass index and insulin resistance, thus
      suggesting a key role of central adiposity in the full expression of the
      "metabolic syndrome."

PMID- 12219873
TI  - Evaluation of the performance of a wrist blood pressure measuring device with a
      position sensor compared to ambulatory 24-hour blood pressure measurements.
AB  - This randomized, single-center, open, within-subject study evaluated the
      performance of the Braun PrecisionSensor 2000 blood pressure (BP) measurement
      wrist device (BP 2000, Braun GmbH, Germany) with and without the position sensor,
      and compared the results with data obtained from 24-h ambulatory BP measurement
      (ABPM, A&D TM 2430). In a crossover design, 43 subjects performed BP measurements
      with the BP 2000 during two 7-day periods, one with the position sensor and the
      other without the position sensor. The correlation coefficients between all wrist
      self-measurements and ABPM were 0.73 for systolic and 0.65 for diastolic BP (with
      position sensor) compared to 0.70 and 0.60 for readings without position sensor,
      respectively. The categorization of subjects as normotensive or hypertensive,
      using the wrist device in subjects without specific training, achieved a correct
      classification of 84% (with position sensor) and 81% (without position sensor) in
      comparison to ABPM. When the measurements were performed in the clinic by an
      experienced observer, the correct classification was 79% in comparison to ABPM.
      The crossover study design did not show any significant variation between the two
      devices with regard to reproducibility of readings at the wrist. In conclusion,
      self-BP measurements with BP 2000, by untrained subjects, produced results
      consistent with those found recently with self-BP measurements with upper arm
      devices, when both data sets are compared with ABPM. The rates of false
      classification of normotension/hypertension with the wrist device were small and
      at least as reliable as office measurements.

PMID- 12219875
TI  - Relaxation and cGMP formation in response to sildenafil and sodium nitroprusside
      in saphenous veins from normotensive and hypertensive patients.
AB  - BACKGROUND: This study was designed to measure cyclic guanosine 3'5'
      monophosphate (cGMP) formation and relaxation response to sildenafil given either
      alone or in combination with sodium nitroprusside in saphenous veins obtained
      from normotensive and hypertensive patients. METHODS: Saphenous vein rings were
      obtained from 13 hypertensive and nine normotensive patients undergoing coronary
      artery bypass surgery. The vein rings were suspended in organ bath chambers for
      isometric recording of tension. The effect of sildenafil on sodium nitroprusside
      induced cGMP formation was also assessed. RESULTS: Sildenafil (10 nmol/L to 100
      micromol/L) and sodium nitroprusside (0.01 to 100 nmol/L) caused concentration
      dependent relaxations that were of greater magnitude in veins from normotensive
      patients. Sildenafil (1 to 10 micromol/L) amplified the relaxation induced by
      sodium nitroprusside in both groups of veins, but this effect was more pronounced
      in veins from hypertensive patients. Levels of cGMP in response to sodium
      nitroprusside were significantly lower in veins from hypertensive subjects.
      However, in the presence of sildenafil, the increase in cGMP levels in response
      to sodium nitroprusside was significantly greater in the hypertensive as compared
      with the normotensive group. CONCLUSIONS: Although the relaxant effects of
      sildenafil are less pronounced in veins from hypertensive patients, the
      synergistic interaction sildenafil-sodium nitroprusside is more effective in
      veins from hypertensive patients, mainly due to an increase in cGMP accumulation.

PMID- 12219874
TI  - Enhanced thromboxane synthesis during chronic reductions in uterine perfusion
      pressure in pregnant rats.
AB  - BACKGROUND: The purpose of this study was to determine the role of thromboxane A2
      (TXA2) in a conscious, chronically instrumented rat model of pregnancy-induced
      hypertension (PIH) produced by chronic reductions in uterine perfusion pressure
      (RUPP). METHODS: Mean arterial pressure (MAP), glomerular filtration rate (GFR),
      effective renal plasma flow (ERPF) and 24-h urinary excretion of TXB2 (metabolite
      of TXA2) were determined in normal pregnant rats and RUPP pregnant rats. RESULTS:
      At day 20 of pregnancy, RUPP rats showed a significantly (P < .05) higher MAP
      (125 +/- 3 mm Hg v 100 +/- 2 mm Hg) as compared with normal pregnant controls.
      The elevation in arterial pressure in RUPP group was associated with a marked
      increase (P < .05) in the urinary concentration of TXB2 compared with normal
      pregnant group (3663 +/- 488 v 2646 +/- 257 pg/24 h). Baseline GFR (1.74 +/- 0.13
      v 2.40 +/- 0.20 mL/min, respectively, P < .05) and ERPF (5.13 +/- 0.44 v 6.44 +/-
      0.58 mL/min, respectively) were decreased in RUPP rats relative to pregnant
      controls. Infusion of a TX receptor antagonist, SQ 29,548 (2 mg/kg bolus plus 2
      mg/kg per h infusion) had no significant effect on increased MAP in RUPP pregnant
      rats. Similarly, ERPF and GFR did not change during acute blockade of TXA2
      receptors in this group. CONCLUSION: These findings suggest that enhanced
      production of TXA2 does not play a major role in mediating the hypertension and
      renal vasoconstriction produced by chronic RUPP in pregnant rats.

PMID- 12219876
TI  - Chronic imidazoline receptor activation in spontaneously hypertensive rats.
AB  - BACKGROUND: Acute intravenous administration of moxonidine, an imidazoline I1
      receptor agonist, reduces blood pressure (BP) in normotensive and hypertensive
      rats, induces diuresis and natriuresis, and stimulates plasma atrial natriuretic
      peptide (ANP). In these studies we investigated the involvement of natriuretic
      peptides (ANP and brain natriuretic peptide) in the effects of chronic activation
      of imidazoline receptors. METHODS: Spontaneously hypertensive rats (SHR; 12 to 14
      weeks old) received 7-day moxonidine treatment at various doses (10, 20, 60, and
      120 microg/kg/h) via subcutaneously implanted osmotic minipumps. RESULTS:
      Hemodynamic parameters (continuously monitored by telemetry) revealed that,
      compared with saline-treated rats, moxonidine dose-dependently decreased blood
      pressures (BPs). Maximal blood pressure lowering effect was achieved by day 4 of
      treatment, at which point 60 microg/kg/h reduced mean arterial pressure (MAP) by
      14.5 +/- 6.8 mm Hg as compared with basal levels. The decrease in MAP was
      influenced by a drop in both diastolic and systolic pressures. Moxonidine
      treatment did not alter daily urinary sodium and potassium excretions, but 120
      microg/kg/h moxonidine decreased urine volume after 2 days and increased cyclic
      guanosine 3'5'monophosphate excretion on days 4 to 7 of treatment. Chronic
      moxonidine treatment dose-dependently increased plasma ANP to reach, at 120
      microg/kg/h, a 40% increase (P < .01) above that of corresponding saline-treated
      SHR, with a concomitant increase in left and right atrial ANP mRNA (more than
      twofold). Plasma BNP increased by 120 microg/kg/h moxonidine (11.0 +/- 1.1 v 16.5
      +/- 1.9 pg/mL, P < .002) without significant increases in atrial and ventricular
      BNP mRNA. CONCLUSIONS: ANP and BNP may be involved in the antihypertensive effect
      of chronic moxonidine treatment. Accordingly, natriuretic peptides may contribute
      to the sympatholytic and cardioprotective effects of chronic activation of
      imidazoline I1-receptors.

PMID- 12219877
TI  - Amplitude and timing of central aortic pressure wave reflections in heart
      transplant recipients.
AB  - BACKGROUND: Hypertension (HTN) assessed by sphygmomanometer is a common finding
      in heart transplant recipients (HTR); however, little is known about the
      contribution of arterial wave reflection to central aortic pressure in these
      patients. The aim of this study was to measure the central aortic pressure wave
      in HTR on antihypertensive therapy and determine the effects of amplitude and
      timing of wave reflection on the various components of the wave. METHODS: A total
      of 53 stable adult HTR on antihypertensive medication underwent brachial artery
      blood pressure ([BP]; by sphygmomanometry) and central aortic pressure (by
      noninvasive radial artery applanation tonometry and use of a generalized transfer
      function) measurements at rest. Central aortic augmentation index (Ala), an
      indicator of arterial stiffness, was calculated from the aortic pressure
      waveform. Patients were divided into three groups (A, B, and C) based on the
      amplitude of AIa. RESULTS: Mean brachial BP was 136 +/- 15/84 +/- 9.4 mm Hg.
      Group A patients (n = 25) had a higher AIa (average 21% +/- 7.6%) than group B (n
      = 18, AIa = 6.5% +/- 3.0%, P < .001) or group C (n = 10, AIa = -8.7% +/- 8.1%, P
      < .001) patients. The amplitude of AIa was inversely related to the travel time
      (delta(t)p/2) of the reflected pressure wave from the periphery to the heart (r =
      -0.78, P < .001). Despite this clear stratification of patients by aortic pulse
      wave analysis, standard cuff pressure was similar among the groups. CONCLUSIONS:
      Noninvasive analysis of the central aortic PRESSURE wave identified a subgroup of
      hypertensive HTR with increased arterial stiffness, increased propagation of the
      reflected wave, and augmented aortic systolic and pulse pressure not identified
      with the sphygmomanometer.

PMID- 12219878
TI  - Additive effect of drospirenone/17-beta-estradiol in hypertensive postmenopausal
      women receiving enalapril.
AB  - BACKGROUND: Aldosterone has been implicated in the pathogenesis of progressive
      cardiovascular disease. Drospirenone (DRSP) is a novel progestin with aldosterone
      receptor antagonist activity developed for hormone replacement therapy (HRT) as
      DRSP/17beta-estradiol (DRSP/ E2). We investigated the additive effect of DRSP/E2
      versus placebo on 24-h ambulatory blood pressure (BP) in postmenopausal women
      with hypertension treated with enalapril maleate (ENA). METHODS: This was a
      double-blind, randomized, two-parallel group trial. Twenty-four nonsmoking
      postmenopausal women receiving 10 mg of ENA twice a day before study were
      randomized to DRSP/E2 + ENA (n = 12) or placebo (P) + ENA (n = 12) for 14 days.
      Twenty-four-hour ambulatory BP, plasma renin activity, and serum aldosterone were
      determined at baseline and on day 14. RESULTS: Compared to placebo, 24-h mean
      [SD] BP in the DRSP/E2 + ENA group decreased significantly from baseline (139/80
      mm Hg), systolic (-9 [51 mm Hg, P = .014) and diastolic (-5 [4] mm Hg, P = .007).
      Essentially no change from baseline (139/83 mm Hg) in systolic or diastolic 24-h
      ambulatory BP were observed in the P + ENA group. Aldosterone (mean [SD])
      increased from baseline by 2.6 [4.5] ng/dL in the DRSP/E2 + ENA group, and
      decreased by 0.3 [5.5] ng/dL in the P + ENA group (P = .08) consistent with an
      antimineralocorticoid effect. CONCLUSIONS: Our results suggest a significant
      additive BP-lowering effect of DRSP/E2 on both systolic and diastolic BP in
      hypertensive postmenopausal women receiving ENA, consistent with an
      antimineralocorticoid effect. DRSP/E2, a HRT with antimineralocorticoid effects,
      could offer a novel potential mechanism for reducing cardiovascular end points in
      postmenopausal women.

PMID- 12219879
TI  - Inflection point of ascending aortic waveform is a powerful predictor of
      restenosis after percutaneous transluminal coronary angioplasty.
AB  - BACKGROUND: Although it was reported that the pulsatility of ascending aortic
      pressure is closely related to restenosis after percutaneous transluminal
      coronary angioplasty (PTCA), it is not known whether the reflection period of
      ascending aortic pressure can predict restenosis after PTCA. The purpose of this
      study was to evaluate whether reflection in the arterial system can be used to
      predict restenosis after PTCA. METHODS: We used the inflection point as the
      reflection period index and measured the coronary artery diameter, aortic
      pressure, and inflection time before PTCA. We defined the inflection time as the
      time interval from the initiation of systolic pressure waveform to the inflection
      point. We prospectively investigated the effect of inflection time in relation to
      the subsequent risk of restenosis after PTCA in patients with coronary artery
      disease. RESULTS: Crude cumulative incidence rates of restenosis were 74.1% for
      the lowest, 33.3% for the middle, and 26.1% for the highest tertile of inflection
      point levels. After adjustments for age, gender, smoking habits, hypertension,
      type 2 diabetes, hypercholesterolemia, old myocardial infarction, vessel
      location, post-minimal lumen diameter, heart rate, and ejection fraction, the
      odds ratio of restenosis was 6.99 (95% confidence interval, 1.54 to 31.7) for the
      lowest tertile of the inflection time level compared with the highest tertile
      level. CONCLUSIONS: Inflection time is a powerful predictor of restenosis after
      PTCA.

PMID- 12219880
TI  - Circadian blood pressure overswinging in a physically fit, normotensive African
      American woman.
AB  - Ambulatory blood pressure (BP) and heart rate (HR) were measured in a physically
      fit, normotensive postmenopausal African American woman, before and after 15
      weeks of aerobic training. Mean BP, HR, and HR variability were normal at the
      outset and were further improved by training. Training had no effect on circadian
      BP variation, which exceeded gender- and age-specified limits, indicative of
      circadian hyperamplitude tension (CHAT). A 12-week treatment with the beta1
      adrenoceptor blocker atenolol, 14 months post-training, normalized CHAT and HR
      variability and further reduced BP and HR. These results suggest beta1-adrenergic
      mediation of CHAT and its refractoriness to exercise training.

PMID- 12219881
TI  - Doxazosin and ALLHAT trial: a response.

PMID- 12219882
TI  - Blood pressure and angiotensin converting enzyme inhibitor use in hypertensive
      patients with chronic renal insufficiency.

PMID- 12219883
TI  - Learning abstract relations from using categories.
AB  - When people learn categories, the importance of the features and relations in the
      category representation reflects both their diagnosticity for classification and
      their relevance to the use of the category. In earlier work in which the
      influence of category use on the representation has been shown, only cases in
      which the features and relations were simple, observable, and very specific were
      examined. Learners may begin to understand the underlying similarities of
      category members by using the categories. In the four experiments presented here,
      learners applied a simple category-specific formula to category members. The test
      results showed that the learners had incorporated relations among features from
      this use, including cases in which the relations were abstract. This learning
      occurred even though the relations were actually not predictive of category
      membership but just perceived to be so as a function of the use.

PMID- 12219884
TI  - Observational versus feedback training in rule-based and information-integration
      category learning.
AB  - The effects of two different kinds of categorization training were investigated.
      In observational training, observers are presented with a category label and then
      shown an exemplar from that category. In feedback training, they are shown an
      exemplar, asked to assign it to a category, and then given feedback about the
      accuracy of their response. These two types of training were compared as
      observers learned two types of category structures--those in which optimal
      accuracy could be achieved via some explicit rule-based strategy, and those in
      which optimal accuracy required integrating information from separate perceptual
      dimensions at some predecisional stage. There was an overall advantage for
      feedback training over observational training, but most importantly, type of
      training interacted strongly with type of category structure. With rule-based
      structures, the effects of training type were small, but with information
      integration structures, accuracy was substantially higher with feedback training,
      and people were less likely to use suboptimal rule-based strategies. The
      implications of these results for current theories of category learning are
      discussed.

PMID- 12219885
TI  - Category induction from distributional cues in an artificial language.
AB  - The ability to identify the grammatical category of a word (e.g., noun, verb,
      adjective) is a fundamental aspect of competence in a natural language. Children
      show evidence of categorization by as early as 18 months, and in some cases
      younger. However, the mechanisms that underlie this ability are not well
      understood. The lexical co-occurrence patterns of words in sentences could
      provide information about word categories--for example, words that follow the in
      English often belong to the same category. As a step in understanding the role
      distributional mechanisms might play in language learning, the present study
      investigated the ability of adults to categorize words on the basis of
      distributional information. Forty participants listened for approximately 6 min
      to sentences in an artificial language and were told that they would later be
      tested on their memory for what they had heard. Participants were next tested on
      an additional set of sentences and asked to report which sentences they
      recognized from the first 6 min. The results suggested that learners performed a
      distributional analysis on the initial set of sentences and recognized sentences
      on the basis of their memory of sequences of categories of words. Thus,
      mechanisms that would be useful in natural language learning were shown to be
      active in adults in an artificial language learning task.

PMID- 12219887
TI  - Efficiency of retrieval correlates with "logical" reasoning from causal
      conditional premises.
AB  - In two experiments, we examined the prediction that there should be a relation
      between the speed with which subjects can retrieve potential causes for given
      effects and their reasoning with causal conditional premises (if cause P, then
      effect Q). It was also predicted that when subjects are given effects for which
      there exists a single strongly associated cause, speed of retrieval of a second
      potential cause should be particularly related to reasoning with invalid logical
      forms--namely, affirmation of the consequent and denial of the antecedent. In the
      first experiment, 49 university students were given both retrieval tasks and
      conditional reasoning problems. The results were generally consistent with the
      predictions. The second experiment, involving 57 university students, replicated
      the first, with some methodological variations. The results were also consistent
      with the predictions. An analysis of the combined results of the two experiments
      indicated that individual differences in efficiency of retrieval of information
      from long-term memory did predict performance on the invalid logical forms in the
      predicted ways. These results strongly support a retrieval model for conditional
      reasoning with causal premises.

PMID- 12219886
TI  - Recent exposure affects artifact naming.
AB  - Deciding how to label an object depends both on beliefs about the culturally
      appropriate name and on memory. A label should be consistent with a language
      community's norms, but those norms can be used only if they can be retrieved. Two
      experiments are reported in which we tested the hypothesis that immediate prior
      exposure to familiar objects and their names affects how an ambiguous target
      object is named. Exposure to a typical instance of one name category was pitted
      against exposure to one or two instances from a contrasting category. When the
      contrast set consisted of a neighbor of the target, naming was usually consistent
      with the contrast category. This effect was reduced when a typical instance of
      the contrast category was also exposed. In Experiment 2, the exposure set was
      varied to include conditions in which either the neighbor or a prototypical
      instance was paired with an instance dissimilar to the target. The results
      suggest that all recently exposed objects affect name choice in proportion to
      their similarity to the target.

PMID- 12219888
TI  - The role of attack and defense semantics in skilled players' memory for chess
      positions.
AB  - There is much evidence that chess skill is based on chunks in memory that
      represent parts of positions from previously encountered games. However, the
      content of these chunks is a matter for debate. According to one view, (1) the
      closer two pieces are to each other on a board (proximity), the more likely they
      are to be in the same chunk, and (2) skilled players encode the precise locations
      of pieces. An alternative view is that what information is encoded in a chess
      chunk is determined more by processing of the attack/defense relations during
      evaluation. In three experiments, participants evaluated positions and completed
      recognition tests. Experiment 1 supported the view that expert players make more
      use of attack/defense relations than of locations of pieces in a recognition
      test. Experiments 2 and 3 demonstrated that, for both long and short presentation
      times, expert players' recognition for a piece within a position was primed more
      by a piece related by attack or defense than by a piece merely proximal. These
      findings challenge theories of expertise for chess that assume a primary role for
      proximity and location in determining which pieces are grouped together in
      memory.

PMID- 12219889
TI  - The time course of spatial memory distortions.
AB  - Four experiments investigated the memory distortions for the location of a dot in
      relation to two horizontally aligned landmarks. In Experiment 1, participants
      reproduced from memory a dot location with respect to the two landmarks. Their
      performance showed a systematic pattern of distortion that was consistent across
      individual participants. The three subsequent experiments investigated the time
      course of spatial memory distortions. Using a visual discrimination task, we were
      able to map the emergence of spatial distortions within the first 800 msec of the
      retention interval. After retention intervals as brief as 50 msec, a distortion
      was already present. In all but one experiment, the distortion increased with
      longer retention intervals. This early onset of spatial memory distortions might
      reflect the almost immediate decay of detailed spatial information and the early
      influence of an enduring spatial memory representation, which encodes spatial
      information in terms of the perceived structure of space.

PMID- 12219890
TI  - Factors modulating the effect of divided attention during retrieval of words.
AB  - In this study, we examined variables modulating interference effects on episodic
      memory under divided attention conditions during retrieval for a list of
      unrelated words. In Experiment 1, we found that distracting tasks that required
      animacy or syllable decisions to visually presented words, without a memory load,
      produced large interference on free recall performance. In Experiment 2, a
      distracting task requiring phonemic decisions about nonsense words produced a far
      larger interference effect than one that required semantic decisions about
      pictures. In Experiment 3, we replicated the effect of the nonsense-word
      distracting task on memory and showed that an equally resource-demanding picture
      based task produced significant interference with memory retrieval, although the
      effect was smaller in magnitude. Taken together, the results suggest that free
      recall is disrupted by competition for phonological or word-form representations
      during retrieval and, to a lesser extent, by competition for semantic
      representations.

PMID- 12219891
TI  - Mechanisms of source confusion and discounting in short-term priming: 1. Effects
      of prime duration and prime recognition.
AB  - Huber, Shriffrin, Lyle, and Ruys (2001) measured short-term repetition priming
      effects in perceptual identification with two-alternative forced-choice testing.
      There was a preference to choose repeated words following passive viewing of
      primes and a preference against choosing repeated words following active
      responding to primes. In this present study, we explored conditions of prime
      processing that produce this pattern of results. Experiment 1 revealed that
      increased prime duration under passive viewing instructions produces the active
      priming pattern. Experiment 2 assessed memory for primes: With poor recognition
      of primes, there was a strong preference for repeated words; however, with good
      recognition of primes, this preference was eliminated. These results are modeled
      by a computational theory of optimal decision making, responding optimally with
      unknown sources of evidence (ROUSE). In ROUSE, a preference for repeated words
      results from source confusion between primes and choice words. A reversal in the
      direction of preference arises from the discounting of words known to have also
      appeared as primes.

PMID- 12219892
TI  - Recognition with and without identification: dissociative effects of meaningful
      encoding.
AB  - In a series of four experiments, the effects of levels of processing and
      generation on the recognition of identified versus unidentified word fragments
      were examined. After studying a list of words, participants took a word fragment
      completion test in which half of the fragments came from studied words and half
      came from nonstudied words. Regardless of whether they could complete a given
      fragment, the participants were asked to rate the likelihood that it came from a
      studied word. Recognition of identified fragments was best whenever the focus of
      the encoding task was on meaning. Recognition of unidentified fragments did not
      benefit from meaningful encoding in any of the experiments reported here but did
      benefit from generation. It is suggested that whereas recognition with
      identification involves the use of meaning, recognition without identification
      involves the use of abstract orthographic information in memory.

PMID- 12219893
TI  - How does background information improve memory for text content?
AB  - In two experiments, we investigated whether reading background information
      benefits memory for text content by influencing the amount of content encoded or
      the organization of the encoded content. In Experiment 1, half of the
      participants read background information about the issues to be discussed in the
      text material, whereas half did not. All the participants were then tested for
      free recall and cued recall of text content. Free recall was greater for
      individuals who read issue information than for those who did not. The groups did
      not differ on cued recall, suggesting that background information did not
      facilitate the encoding of more text content. Measures of representational
      organization indicated that increased recall in the issue information group
      resulted from better organization of content in memory. Experiment 2 extended
      these findings, using background information about text sources, demonstrated
      that the efficacy of background information depends on the semantic relationship
      between that information and text content.

PMID- 12219894
TI  - Readers' reality-driven and plot-driven analyses in narrative comprehension.
AB  - We suggest that when readers experience narratives, their expectations about the
      likelihood of narrative events are informed by two types of analyses. Reality
      driven analyses incorporate real-world constraints involving, for example, time
      and space; plot-driven analyses incorporate concerns about outcomes that emerge
      from the plot. We explored the interaction of these two types of analyses in the
      application of temporal situation models. Participants read stories in which the
      final episode occurred after a minute time shift (i.e., "A minute later...") or
      hour time shift (i.e., "An hour later..."). Our experiments assessed
      participants' judgments and reading times for statements describing the state of
      events (e.g., the possibility that characters could carry out particular
      behaviors) following each type of time shift. Experiments 1A and 1B demonstrated
      that readers are appropriately sensitive to the real concomitants of time shifts.
      Experiments 2A and 2B demonstrated, even so, that plot-driven preferences modify
      judgments and reading times away from reality-driven expectations. Our results
      have implications for the role of the reader in theories of narrative
      comprehension.

PMID- 12219895
TI  - Presenting two color words on a single Stroop trial: evidence for joint
      influence, not capture.
AB  - MacLeod and Hodder (1998) demonstrated that presenting two different incongruent
      color words in the same color on a single Stroop trial resulted in no more
      interference than did presenting the same incongruent color word twice, and
      concluded that the first word captured attention, blocking out the second. They
      also showed that, within a trial, neither stimulus onset asynchrony between the
      two items nor the presence/absence of a visible gap between the two items had any
      effect. We replicated all of their empirical findings. Then, by extending their
      design and factorially combining three types of items--incongruent words,
      congruent words, and control nonwords--within a trial, we demonstrated that both
      items within a trial do influence processing, with the contribution of the second
      greater than that of the first. These results are incompatible with a capture
      account and suggest instead that the word dimension continues to be monitored
      during the attempt to identify and produce the name of the color.

PMID- 12219896
TI  - Perception of resyllabification in French.
AB  - In three experiments, we examined the effects of phonological resyllabification
      processes on the perception of French speech. Enchainment involves the
      resyllabification of a word-final consonant across a syllable boundary (e.g., in
      chaque avion, the /k/ crosses the syllable boundary to become syllable initial).
      Liaison involves a further process of realization of a latent consonant,
      alongside resyllabification (e.g., the /t/ in petit avion). If the syllable is a
      dominant unit of perception in French (Mehler, Dommergues, Frauenfelder, & Segui,
      1981), these processes should cause problems for recognition of the following
      word. A cross-modal priming experiment showed no cost attached to either type of
      resyllabification in terms of reduced activation of the following word.
      Furthermore, word- and sequence-monitoring experiments again showed no cost and
      suggested that the recognition of vowel-initial words may be facilitated when
      they are preceded by a word that had undergone resyllabification through
      enchainment or liaison. We examine the sources of information that could underpin
      facilitation and propose a refinement of the syllable's role in the perception of
      French speech.

PMID- 12219898
TI  - Lords look into animal experimentation.

PMID- 12219899
TI  - Prevalence of Bartonella species causing bacteraemia in domesticated and
      companion animals in the United Kingdom.
AB  - Between October 1999 and February 2000, 691 blood samples examined routinely for
      either haematological or virological assessment were screened by culture for the
      presence of Bartonella species. They came from 615 animals: 360 cats, 211 dogs,
      27 horses, 16 cattle and a gorilla. The samples were incubated for long periods
      on 10 per cent horse blood agar at 37 degrees C in an atmosphere containing 5 per
      cent carbon dioxide. Isolates were obtained from 35 samples from 34 (9.4 per
      cent) of the cats, but not from any of the other animals. Comparison of citrate
      synthase gene sequences from the isolates indicated that they were all Bartonella
      henselae. Analysis of 16S rRNA gene fragments indicated that 30 of the cats were
      infected solely with B henselae genotype II, two were infected solely with B
      henselae genotype I and two were infected with both genotypes.

PMID- 12219897
TI  - The use of word-picture verification to study entry-level object recognition:
      further support for view-invariant mechanisms.
AB  - There are substantial logical and empirical reasons for rejecting the popular
      view that plane-misoriented objects are identified after normalization of global
      orientation. Our subjects determined the entry-level identity of common objects
      (line drawings) before determining basic orientation (upright vs. rotated)--as
      they must if they are to begin to know how to restore the image to the canonical
      upright. We used a description-picture matching procedure in which 7596 of the
      trials involved a mismatch in identity, orientation, or both, so that comparisons
      could be based on one response (no). Times to verify identity were faster than
      times to verify orientation and did not increase with rotations in the picture
      plane. That mismatch objects were positively identified at the entry level was
      shown both in a surprise recognition test for object names and through the
      transfer of priming from the matching task to a subsequent object-naming task. We
      conclude that classic mental rotation-like effects on naming times do not reflect
      early object encoding and recognition processes, which are view invariant, but
      may stem from double-checking at a postrecognition verification stage.

PMID- 12219900
TI  - Prevalence of fragmented medial coronoid process of the ulna in lame adult dogs.
AB  - Over a period of three years, a diagnosis of fragmented medial coronoid process
      of the ulna was confirmed by arthroscopy in 263 dogs, in 69 of which both elbow
      joints were affected, giving a total of 332 affected joints; 39 of the joints
      were also affected by osteochondrosis dissecans of the trochlea of the humerus.
      More than half of the dogs (51.7 per cent) were over one year old when first
      examined. In 259 (78 per cent) of the joints there were radiographic changes of
      secondary osteoarthrosis of different severity, but the other 73 (22 per cent)
      had no signs of osteophytosis except for a mild sclerosis. Among these 73 there
      were 14 joints in 13 dogs between 19 and 36 months old and 11 joints in 10 dogs
      over three years old. A further 12 joints in 11 dogs over three years old showed
      only mild arthrosis. In five of the 11 joints of the dogs over three years old
      which had no radiological signs of arthrosis, the fragment was already
      dislocated. Among the dogs over 18 months old with no arthrosis and the dogs over
      three years old with mild arthrosis, the most commonly affected breeds were the
      Bernese mountain dog, rottweiler and boxer.

PMID- 12219901
TI  - Effects of age, size and condition of elephant seals (Mirounga leonina) on their
      intravenous anaesthesia with tiletamine and zolazepam.
AB  - Southern elephant seals (Mirounga leonina) were caught as part of a long-term
      demographic study on Macquarie Island. Over 18 months, 1033 seals were caught by
      hand and anaesthetised intravenously with a 1:1 mixture of tiletamine and
      zolazepam. Assessments were made of the effects of variations in the body
      condition and age at capture of the seals on the characteristics of their
      anaesthesia, including induction time and weighted recovery time. The size and
      condition of the seals were assessed by morphometric and ultrasound measurements.
      Weighted recovery times decreased as the body condition and age of the seals
      increased, but there were no residual effects of sex. There were no fatalities,
      and no periods of apnoea longer than five minutes were recorded. In individual
      seals there was a significant increase in weighted recovery time with successive
      captures.

PMID- 12219902
TI  - Prevalence and aetiology of clinical mastitis on dairy farms in Devon.

PMID- 12219903
TI  - Computed tomography after mild head trauma in dogs.

PMID- 12219904
TI  - Prevention of oestradiol-associated toxicosis in a dalmatian by early
      intervention with granulocyte colony-stimulating factor.

PMID- 12219905
TI  - Canine brucellosis in a dog imported into the UK.

PMID- 12219906
TI  - Hunting debate.

PMID- 12219907
TI  - BVA governance.

PMID- 12219908
TI  - BVA governance. British Veterinary Association.

PMID- 12219909
TI  - Hunting debate.

PMID- 12219910
TI  - Clinical mastitis in British dairy herds.

PMID- 12219911
TI  - Amblyomma hebraeum is a vector of Rickettsia africae and not R. conorii.

PMID- 12219912
TI  - Evaluation of a commercially available molybdate formulation and zinc oxide
      boluses in preventing hepatic copper accumulation and thus enzootic icterus in
      sheep.
AB  - The efficacy of a molybdate formulation and a zinc oxide bolus as prophylactic
      agents for enzootic icterus was evaluated in sheep. Before copper loading, liver
      biopsies were performed on 12 male, 6-month-old, Mutton Merino sheep to determine
      hepatic copper (Cu) and zinc (Zn) concentrations. The animals were restrictively
      randomised according to liver copper concentrations to 3 treatment groups (n = 4)
      to achieve similar mean liver copper concentrations per group. All sheep received
      4 ml/kg of a 0.5 % aqueous solution of CuSO4 5H2O intraruminally 7 days per week
      for 10 weeks. On Day 0 the sheep in the Mo-group were injected subcutaneously
      with 42 mg molybdenum (Mo) contained in a commercial molybdate formulation. The
      animals in the Zn-group each received a zinc oxide bolus, containing 43 g zinc
      oxide, via a rumen cannula. Treatment was repeated on Day 42. Four animals served
      as untreated controls. Urinary copper excretion, plasma copper concentration,
      haematocrit and glutamate dehydrogenase (GLDH) activity were determined
      throughout the trial. The animals were sacrificed after 10 weeks and liver
      samples were submitted for histopathological examination. Liver and kidney copper
      and zinc concentrations were determined. Neither the molybdate treatment nor the
      zinc oxide boluses prevented hepatic copper accumulation. The urinary copper
      excretion, plasma copper concentration, haematocrit and GLDH activity were not
      significantly different (P > 0.05) from the controls.

PMID- 12219913
TI  - Use of ethnoveterinary medicinal plants in cattle by Setswana-speaking people in
      the Madikwe area of the North West Province of South Africa.
AB  - Rapid Rural Appraisal (RRA) methods were employed to document the use of
      ethnoveterinary medicinal plants in cattle by Setswana-speaking people in the
      Madikwe area of the North West Province of South Africa. The study indicated that
      Setswana-speaking people in the North West Province have a rich heritage of
      ethnoveterinary knowledge, which includes all aspects of ethnoveterinary
      medicinal plant use. Information was gathered from informants through individual
      interviews, group interviews, guided field walks and observations.
      Ethnoveterinary uses in cattle of 45 plant species representing 24 families were
      recorded. Plants were used in 84% of the total number of recorded ethnoveterinary
      remedies. These plants were used alone (64%) or in mixtures (36%) for 29
      indications. The most important indications were retained placenta, diarrhoea,
      gallsickness, fractures, eye inflammation, general ailments, fertility
      enhancement, general gastrointestinal problems, heartwater, internal parasites,
      coughing, redwater and reduction of tick burden. Plant materials were prepared in
      various ways including infusion, decoction, ground fresh material, sap expressed
      from fresh material, charred and dried. The most common dosage form was a liquid
      for oral dosing. Other dosage forms included drops, licks, ointments, lotions and
      powders. Liquid remedies for oral dosing were always administered using a bottle.
      Medicinal plant material was preferably stored in a dried form in a cool place
      out of direct sunlight and wind. Lack of transfer of ethnoveterinary knowledge to
      younger generations puts this knowledge at risk. RRA was found to be a successful
      method of investigation for the study of ethnoveterinary medicine.

PMID- 12219914
TI  - Factors related to high levels of ostrich chick mortality from hatching to 90
      days of age in an intensive rearing system.
AB  - Ostrich chick mortality was studied in 2522 chicks that were hatched artificially
      during the 1999/2000 breeding season. High levels of mortality were observed,
      with 1978 (78.4 %) of these chicks dying before 90 days after hatching. A total
      of 46.7 % (1,177) of these chicks died before 28 days of age, and a further 30.7%
      (801) died between 28 and 90 days post-hatching. Chick mortality to 28 days of
      age could not be conclusively related to sex, day of external pipping or breeder
      diet. Mortality rates were higher (P< 0.05) at the beginning and end of the
      breeding season than in the middle months. Differences in mortality levels of
      chicks incubated in different incubators could be related to the time of the
      breeding season during which the incubator was mostly used. The regression of
      chick mortality to 28 days of age on day-old chick mass followed a 2nd-degree
      polynomial. Chicks with day-old masses below 762.5 g were particularly at risk of
      dying before 28 days after hatching. Chicks hatching from eggs where excessive
      water loss to 35 days of incubation (>18%) was recorded were also at risk of
      succumbing before 28 days of age. Chick mortality percentages for the period from
      28 to 90 days of age exceeded 80 % in chicks weighing an average of 1.050 g at 28
      days. Mortality percentages declined sharply at higher live masses, to between 20
      and 30 % in chicks weighing > or = 1,950 g. This 'core' level of mortality
      remained throughout, even in the heaviest chicks. It was concluded that the high
      levels of chick mortality could be related to stress in chicks, resulting from an
      inability to adapt to the rearing environment. The high subsequent mortality
      percentages of low live mass chicks that survived to 28 days after hatching could
      probably be attributed to residual setbacks suffered earlier. Abetter
      understanding of the underlying principles involved in ostrich chick mortality in
      intensive rearing environments is required for progress in this field, resulting
      in more predictable survival rates under these conditions.

PMID- 12219915
TI  - Radiographic anatomy of the thoraco-abdominal cavity of the ostrich (Struthio
      camelus).
AB  - This study provides a reference for the radiographic anatomy of the thoraco
      abdominal cavity of female ostriches as a representative of ratites. One ostrich
      cadaver, 2 adult and 2 growing ostriches were used. Right lateral radiographs
      produced by a 6-frame technique and 2 dorsoventral radiographs produced by an
      adapted 3-frame technique were selected and schematic illustrations of these were
      labelled to illustrate normal radiographic anatomy. Differences from other avian
      species and unique features of the ostrich are briefly discussed.

PMID- 12219916
TI  - Veterinary needs of dogs in two resource-limited communities in the Gauteng and
      North West provinces of South Africa.
AB  - Information on the socioeconomic aspects and the health status of dogs in 2
      resource-limited communities in the North West and Gauteng provinces of South
      Africa was gathered using semi-structured interviews and a standardised
      questionnaire. The dogs were examined clinically to determine their health
      status, and their body condition and age were scored. Most of the dogs (93 % in
      Jericho and 90 % in Zuurbekom) were infected with hookworm, which poses a threat
      to animal and human health in the 2 study areas. Many dogs were also being given
      a protein-deficient diet, which together with hookworm parasites would impact
      considerably on the dog's health. Dogs were mainly kept for security reasons. The
      need indicated tobe most important by the residents of the 2 communities was a
      lack of available and affordable veterinary services.

PMID- 12219917
TI  - Some clinical effects of midazolam premedication in propofol-induced and
      isoflurane-maintained anaesthesia in dogs during ovariohysterectomy.
AB  - In a randomised, placebo-controlled clinical trial, anaesthesia was induced with
      propofol (4 mg/kg) after intravenous premedication with or without midazolam (0.1
      mg/kg), in a group of 8 dogs scheduled for ovariohysterectomy. Midazolam
      administration induced acute behavioural changes, and increased reflex
      suppression after propofol induction. Compared to the control group, the dose
      required to obtain loss of the pedal reflex was significantly reduced by 37%, and
      the end-tidal isoflurane concentration during maintenance, reduced by 23%.

PMID- 12219918
TI  - The effect of frog pressure and downward vertical load on hoof wall weight
      bearing and third phalanx displacement in the horse--an in vitro study.
AB  - A shoe was designed to combine the advantages of a reverse shoe and an adjustable
      heart bar shoe in the treatment of chronic laminitis. This reverse even frog
      pressure (REFP) shoe applies pressure uniformly over a large area of the frog
      solar surface. Pressure is applied vertically upward parallel to the solar
      surface of the frog and can be increased or decreased as required. Five
      clinically healthy horses were humanely euthanased and their dismembered
      forelimbs used in an in vitro study. Frog pressure was measured by strain gauges
      applied to the ground surface of the carrying tab portion of the shoe. A linear
      variable distance transducer (LVDT) was inserted into a hole drilled in the
      dorsal hoof wall. The LVDT measured movement of the third phalanx (P3) in a
      dorsopalmar plane relative to the dorsal hoof wall. The vertical component of
      hoof wall compression was measured by means of unidirectional strain gauges
      attached to the toe, quarter and heel of the medial hoof wall of each specimen.
      The entire limb was mounted vertically in a tensile testing machine and submitted
      to vertical downward compressive forces of 0 to 2,500 N at a rate of 5 cm/minute.
      The effects of increasing frog pressure on hoof wall weight-bearing and third
      phalanx movement within the hoof were determined. Each specimen was tested with
      the shoe under the following conditions: zero frog pressure; frog pressure used
      to treat clinical cases of chronic laminitis (7 N-cm); frog pressure clinically
      painful to the horse as determined prior to euthanasia; frog pressure just
      alleviating this pain. The specimens were also tested after shoe removal. Total
      weight-bearing on the hoof wall at zero frog pressure was used as the basis for
      comparison. Pain-causing and pain-alleviating frog pressures decreased total
      weight-bearing on the hoof wall (P < 0.05). Frog pressure of 7 N-cm had no
      statistically significant effect on hoof wall weight-bearing although there was a
      trend for it to decrease as load increased. Before loading, the pain-causing and
      pain-alleviating frog pressures resulted in a palmar movement of P3 relative to
      the dorsal hoof wall compared to the position of P3 at zero frog pressure (P <
      0.05). This difference remained statistically significant up to 1300 N load. At
      higher loads, the position of P3 did not differ significantly for the different
      frog pressures applied. It is concluded that increased frogpressure using the
      REFP shoe decreases total hoof wall weight-bearing and causes palmar movement of
      P3 at low weight-bearing loads. Without a shoe the toe and quarter hoof wall
      compression remained more constant and less in magnitude, than with a shoe.

PMID- 12219919
TI  - Out-of-season breeding of milk goats--the effect of light treatment, melatonin
      and breed.
AB  - The purpose of this study was to evaluate the effectivity of melatonin in
      addition to light treatment (exposure to 2 hours of light during the night = a
      long-day photoperiod) to modify the breeding season of Saanen and cross-bred milk
      goats and to compare the difference between the breeds. Twenty-two Saanen and 22
      cross-bred does were randomly divided into 3 treatment groups. Group 1 (controls)
      received no treatment, Group 2 received light treatment for 37 days and Group 3
      received light treatment plus melatonin implants after the light treatment. After
      a further 35 days the 3 groups were brought together and a billy goat that had
      also been exposed to the extra light at night, had received a melatonin implant
      and had been isolated from the does during the treatment period, was introduced
      to the does for natural mating. Ultrasound scanning was used to diagnose
      pregnancy and all the pregnant goats kidded. Significantly more Saanen does
      compared to cross-bred does (P = 0.018) became pregnant and kidded after natural
      mating, when the group that received melatonin as well as light treatment was
      compared to the group that received light treatment only. Compared to light
      treatment only, the addition of melatonin to light treatment improved (P =
      0.0028) conception after natural mating, in both the Saanen and the cross-bred
      does.

PMID- 12219920
TI  - The resurgence of trypanosomosis in Botswana.
AB  - No sleeping sickness or nagana cases have been reported in Botswana since 1985.
      In view of several confirmed clinical cases of nagana and reports of heavy bovine
      mortality, a parasitological survey was conducted to determine the prevalence of
      trypanosome infection in cattle in Maun and Shakawe areas of Ngamiland district.
      Wet blood films, buffy coat and Giemsa-stained thick and thin blood smears were
      used to detect trypanosomes in animals. Overall,trypanosome infection rate was
      15.98%, with 5.94% and 27.29% in Maun and Shakawe respectively. The urgent need
      to combat trypanosomosis in Ngamiland, particularly in the Shakawe area, is
      highlighted, and a 3-phase integrated tsetse control strategy for this disease
      problem is discussed.

PMID- 12219921
TI  - The first reported case of equine nocardioform placentitis in South Africa.
AB  - Since the late 1980s a distinct form of focally-extensive mucoid to mucopurulent
      uterine body chronic placentitis,caused by nocardioform organisms, hasbeen
      recognised in horses in the USA state of Kentucky and possibly in other areas.
      This disease has led to increasing numbers of foal losses from late abortions,
      still-births, prematurity, or early neonatal deaths. The foals are usually not
      infected, but may be small or emaciated. Modes of infection and transmission are
      as yet unknown. Nocardia spp. and related nocardioform bacteria as causes of
      equine infertility, endometritis and foal death are briefly reviewed. A case of
      near full-term abortion involving a Friesian mare in the Pretoria district of
      Gauteng Province in South Africa during February 2000, with the same placental
      lesion as described in the Kentucky cases, is presented. Nocardioform organisms
      were visualised on impression smears and histological sections of affected foetal
      membranes, and were also cultured. The organism has been identified at the
      Livestock Disease Diagnostic Center of the University of Kentucky as an
      Amycolatopsis sp. of the less-commonly diagnosed group of nocardioforms causing
      placentitis in the USA. The organism was cultured from the uterus of the mare 18
      days post-foaling, but after a 2-week course of oral trimethoprim and
      sulphamethoxazole, based on antibiogram sensitivity testing, a uterine flush
      yielded no growth. A semen sample from the sire of the aborted foal did not yield
      any Gram-positive filamentous branching bacteria. The mare subsequently conceived
      to a single insemination.

PMID- 12219922
TI  - Rectal prolapse associated with a healed pelvic fracture in a pregnant free
      ranging African black rhinoceros (Diceros bicornis). Part 1: anaesthesia.
AB  - Anaesthesia was required in a heavily-pregnant, adult, free-ranging African black
      rhinoceros Diceros bicornis with a rectal prolapse for examination and possible
      treatment. The animal was immobilised with 4.5 mg etorphine and 60 mg azaperone.
      For continued observation, the immobilised animal was transported to a boma.
      Additional etorphine and azaperone were administered to keep the animal
      anaesthetised during treatment and transport. In addition, 15 mg nalorphine was
      administered during this time to improve ventilation and reduce muscle rigidity.
      Sixty hours later, in preparation for surgery, 2.5 mg etorphine and 40 mg
      azaperone were administered, followed by endotracheal intubation and halothane
      anaesthesia. During anaesthesia, a decrease in tidal volume was observed. Venous
      blood-gas analysis indicated a decrease in the oxygen partial pressure, and a
      mixed respiratory and metabolic acidosis. Cardiac arrest was preceded by an
      increase in heart rate and tidal volume after 80 min of inhalation anaesthesia.

PMID- 12219923
TI  - Rectal prolapse associated with a healed pelvic fracture in a pregnant free
      ranging African black rhinoceros (Diceros bicornis). Part 2: surgery and
      necropsy.
AB  - The oedematous and traumatised protruding section of the rectal tissue of an
      adult free-ranging female African black rhinoceros (Diceros bicornis) was
      surgically amputated. Immediately before completion of surgery, the rhinoceros
      died of anaesthetic-related cardiac arrest. At necropsy a deformed pelvis and
      sacrum associated with a healed fracture of the left ileal wing were noted. New
      bone formation in and around the left ventral sacral foramina may have resulted
      in neuropathy of particularly the 3rd and 4th left ventral sacral nerves, which
      (in the horse) supply the majority of the nerve fibres innervating the caudal
      rectum and anus. The cause of the injury is not known, although back injuries,
      presumably sustained during mating by bulls, have been recorded in white
      rhinoceros. An encounter with elephants could also have been responsible for the
      injury in this case.

PMID- 12219924
TI  - Analysis of the Cinchona alkaloids by high-performance liquid chromatography and
      other separation techniques.
AB  - The Cinchona alkaloids, which include the pharmaceuticals quinine and quinidine,
      continue to have a wide variety of important uses. A number of different
      chromatographic procedures have been developed for the qualitative and
      quantitative analysis of these compounds in a variety of sample matrices.
      Reversed-phase HPLC using ODS columns in combination with acidic mobile phases,
      and UV detection, is the most widely used method. Nevertheless, precautions need
      to be taken due to the strong silanophilic interactions which can occur with
      these analytes and the column surface, which can lead to poor peak shape and
      resolution. Different selectivity may be achieved in HPLC separations by use of
      alternative stationary phases, or by varying mobile phase pH. The specificity of
      detection systems may be improved by use of photodiode array UV detectors, or
      especially mass spectrometers. Thin-layer chromatography (TLC) provides a cheap
      alternative analytical method, which is especially useful for qualitative
      analysis. High-performance TLC, gas chromatography, capillary electrophoresis and
      capillary electrochromatography are all methods which after some development,
      could prove useful for Cinchona alkaloid separations.

PMID- 12219925
TI  - Review of the analytical techniques for sesquiterpenes and sesquiterpene
      lactones.
AB  - In this paper the analytical techniques of about the last 2 decades for
      sesquiterpenes including their lactones are reviewed. For sesquiterpenes, methods
      like GC, GC-EI-MS, GC-CI-MS, GC-MS-MS, GC-FT-IR, GC-UV, GC-AES, 13C-NMR, PY-GC
      MS, HPLC, HPLC-TSP, SFE, SFC, SFC-UV are available, GC combined with MS is the
      most widespread. Sesquiterpene lactones can be analysed by HPLC, HPLC-TSP, HPLC
      APCI, HPLC-ESI, HPLC-PB, HPLC-NMR, SFC, MEKC, GC, GC-MS, TLC and OPLC. Here HPLC
      is the method of choice. The usefulness of the individual methods are briefly
      discussed.

PMID- 12219926
TI  - Determination of valepotriates.
AB  - In this paper an overview is given of qualitative and quantitative methods of
      analysis used for valepotriates. Methods like spectophotometry, titrimetry, TLC,
      GC, HPLC, MS, CE as well as p-SFC have been applied. Today HPLC is the method of
      choice. The usefulness of the individual methods are discussed.

PMID- 12219927
TI  - Chromatographic determination of plant saponins.
AB  - The methods used for saponin determination in plant materials are presented. It
      is emphasised that the biological and spectrophotomeric methods still being used
      for saponin determination provide, to some extent, valuable results on saponin
      concentrations in plant material. However, since they are sensitive to the
      structural variation of individual saponins they should be standardized with
      saponin mixtures isolated from the plant species in which the concentration is
      measured. However, one plant species may contain some saponins which can be
      determined with a biological test and others which cannot. That is why biological
      and colorimetric determinations do not provide accurate data and have to be
      recognized as approximate. Thin-layer chromatography on normal and reversed
      phases (TLC, HPTLC, 2D-TLC) provides excellent qualitative information and in
      combination with on-line coupling of a computer with dual-wavelength flying-spot
      scanner and two-dimensional analytical software can be used for routine
      determination of saponins in plant material. The densitometry of saponins has
      been very sensitive, however, to plate quality, spraying technique and the
      heating time and therefore appropriate saponin standards have to be run in
      parallel with the sample. Gas-liquid chromatography has limited application for
      determination since saponins are quite big molecules and are not volatile
      compounds. Thus, there are only few applications of GC for determination of
      intact saponins. The method has been used for determination of TMS, acetyl or
      methyl derivatives of an aglycones released during saponin hydrolysis. However,
      structurally different saponins show different rates of hydrolysis and precise
      optimisation of hydrolysis conditions is essential. Besides, during hydrolysis a
      number of artefacts can be formed which can influence the final results. High
      performance liquid chromatography on reversed-phase columns remains the best
      technique for saponin determination and is the most-widely used method for this
      group of compounds. However, the lack of chromophores allowing detection in UV,
      limits the choice of gradient and detection method. The pre-column derivatisation
      with benzoyl chloride, coumarin or 4-bromophenacyl bromide has been used
      successfully in some cases allowing UV detection of separation. Standardisation
      and identification of the peaks in HPLC chromatograms has been based on
      comparison of the retention times with those observed for authentic standards.
      But new hyphenated techniques, combining HPLC with mass spectrometry and nuclear
      magnetic resonance are developing rapidly and allow on-line identification of
      separated saponins. Capillary electrophoresis has been applied for saponin
      determination only in a limited number of cases and this method is still being
      developed.

PMID- 12219928
TI  - Chromatography and electrophoresis in separation and characterization of
      polysaccharides from lichens.

PMID- 12219929
TI  - Chemical analysis of Ginkgo biloba leaves and extracts.
AB  - The chemical analysis and quality control of Ginkgo leaves and extracts is
      reviewed. Important constituents present in the medicinally used leaves are the
      terpene trilactones, i.e., ginkgolides A, B, C, J and bilobalide, many flavonol
      glycosides, biflavones, proanthocyanidins, alkylphenols, simple phenolic acids, 6
      hydroxykynurenic acid, 4-O-methylpyridoxine and polyprenols. In the commercially
      important Ginkgo extracts some of these compound classes are no longer present.
      Many publications deal with the analysis of the unique terpene trilactones. They
      can be extracted with aqueous acetone or aqueous methanol but also supercritical
      fluid extraction is possible. Still somewhat problematic is their sample clean
      up. Various procedures, not all of them validated, employing partitioning or SPE
      have been proposed. Some further development in this area can be foreseen.
      Separation and detection can be routinely carried out by HPLC with RI, ELSD or
      MS, or with GC-FID after silylation. TLC is another possibility. No quantitative
      procedure for flavonol glycosides has been published so far due their difficult
      separation and commercial unavailability. Fingerprint analysis by gradient RP
      HPLC is possible. After acidic hydrolysis to the aglycones quercetin, kaempferol
      and isorhamnetin and separation by HPLC, quantitation is straightforward and
      yields by recalculation an estimation of the original total flavonol glycoside
      content. For biflavones, simple phenols, 6-hydroxykynurenic acid, 4-O
      methylpyridoxine and polyprenols analytical procedures have been published but
      not all assays are yet ideal. Lately a there is a lot of interest in the analysis
      of the undesired alkylphenols and a few validated procedures have been published.
      The analysis of Ginkgo proanthocyanidins is still in its infancy and no reliable
      assays exist.

PMID- 12219930
TI  - Polyhydroxy alkaloids: chromatographic analysis.
AB  - Polyhydroxy alkaloids are a burgeoning category of natural products that
      encompass several structural types and generally exhibit potent activity as
      inhibitors of glycosidases. As presently defined the group consists of monocyclic
      or bicyclic aLkaloids of the pyrrolidine, piperidine, pyrrolizidine, indolizidine
      and tropane classes, bearing two or more hydroxyl groups. These structural
      features render the compounds highly water soluble and frequently quite insoluble
      in non-hydroxylic solvents, so that their isolation and analysis by
      chromatographic means are consequently difficult. This problem is further
      confounded by the lack of a chromophore which would permit their detection by UV
      absorption. This review presents chromatographic techniques that have been
      successfully applied to the problem of isolating, purifying, detecting and
      analyzing polyhydroxy alkaloids.

PMID- 12219931
TI  - Chromatography of the chromone and flavonoid alkaloids.
AB  - TLC methods have been derived for the qualitative investigation of the small
      group of compounds known as chromone and flavonoid alkaloids. Quantitation of two
      of the chromone alkaloids has been achieved by HPLC and a graphite column has
      been used to separate the unstable stereoisomers of the piperidone chromone
      alkaloids. A variety of preparative methods, including silica column and droplet
      counter-current chromatography, has been used to isolate the members of this
      group of compounds from plant extracts.

PMID- 12219932
TI  - High-performance liquid chromatographic, capillary electrophoretic and capillary
      electrophoretic-electrospray ionisation mass spectrometric analysis of selected
      alkaloid groups.
AB  - Systems for efficient separation of selected alkaloid groups by high performance
      liquid chromatography (HPLC), capillary electrophoresis (CE) and capillary
      electrophoresis coupled with electrospray ionisation mass spectrometry (CE-ESI
      MS) are described. The optimized HPLC system was applied for the separation of 23
      standard indole alkaloids as well as for qualitative and quantitative analyses of
      crude alkaloid extracts of Rauvolfia serpentina X Rhazya stricta hybrid cell
      cultures. The developed conditions for CE analysis proved to be efficient for
      separation of mixtures of standard indole and beta-carboline alkaloids. The
      described buffer system is also applicable in the combination of CE with
      electrospray ionisation mass spectrometry. This analytical technique allowed the
      separation and identification of components of standard indole alkaloid mixture
      as well as crude extracts of R. serpentina roots, R. serpentina cell suspension
      cultures and cortex of Aspidosperma quebracho-blanco. The influence of buffer
      composition and analyte structures on separation is discussed.

PMID- 12219933
TI  - In vitro maturation and glutathione synthesis of porcine oocytes in the presence
      or absence of cysteamine under different oxygen tensions: role of cumulus cells.
AB  - The present study was conducted to evaluate the effect of cumulus cells on the in
      vitro maturation (IVM) and glutathione (GSH) synthesis of porcine oocytes
      cultured in the presence or absence of cysteamine under different oxygen
      tensions, and on their subsequent male pronucleus formation after in vitro
      fertilization (IVF). Cumulus-oocyte complexes (COCs) and cumulus-denuded oocytes
      (DOs) were cultured for 45 h in modified TCM-199 supplemented with or without 150
      microM cysteamine under a humidified atmosphere of 5% CO2 in air (20% O2) or 5%
      CO2, 5% O2 and 90% N2. When cultured in medium supplemented with cysteamine under
      20% O2 tension, the rates of COC maturation to the metaphase II (MII) stage were
      significantly higher than those of DOs (P<0.05). Regardless of the addition of
      cysteamine and oxygen tension, the rates of male pronucleus formation in COCs
      after IVM and IVF were significantly higher than in DOs (P<0.05). The GSH content
      of oocytes was significantly increased by the addition of cysteamine to the
      maturation medium (P<0.05), with significantly higher GSH content in COCs than in
      DOs (P<0.05). However, the GSH content of COCs and DOs was not significantly
      different when cultured in medium without cysteamine. These results indicate that
      cumulus cells play an important role in nuclear maturation to MII, GSH synthesis
      in porcine oocytes cultured in the presence of cysteamine, and subsequent male
      pronucleus formation after IVF.

PMID- 12219934
TI  - Paradoxical effects of tumour necrosis factor-alpha on rat granulosa cell DNA
      synthesis.
AB  - Tumour necrosis factor-alpha (TNF-alpha) has been proposed as an intraovarian
      modulator of granulosa cell function. The effect of TNF-alpha on DNA synthesis in
      cultured rat granulosa cells was examined. Tumour necrosis factor-alpha
      stimulated thymidine incorporation when added in the presence of transforming
      growth factor-beta (TGF-beta). In contrast, the co-mitogenic effect of follicle
      stimulating hormone (FSH) and TGF-beta was inhibited in a dose-dependent manner
      by TNF-alpha. Inhibition of FSH-dependent DNA synthesis by TNF-alpha was also
      found when cultures were co-stimulated with activin A. The inhibitory action of
      TNF-alpha on FSH-treated cultures was not associated with changes in cell
      viability. The inhibitory effects of TNF-alpha could not be solely explained by a
      decrease in cAMP levels, since TNF-alpha was also able to inhibit the stimulation
      by dibutyryl-cAMP and TGF-beta on granulosa cell DNA synthesis. These results
      suggest that TNF-alpha regulation of granulosa cell growth is elicited either
      independently or downstream from gonadotrophin-induced cAMP production. The
      actions of TNF-alpha could be only partially mimicked by a cell-permeable
      analogue of ceramide, thus indicating that actions of this cytokine can not be
      fully ascribed to an activation of sphingomyelinase. Data presented here indicate
      that, in addition to its previously demonstrated inhibitory effects on
      gonadotrophin-induced cell differentiation, TNF-alpha may also exert a marked
      inhibition on hormonally stimulated immature granulosa cell proliferation. In
      contrast to this inhibitory action, this cytokine could amplify the mitogenic
      action of putative intraovarian growth regulators such as TGF-beta. These
      observations add further support to the notion that TNF-alpha plays a
      physiological role as a paracrine modulator of follicle development and may be
      also relevant to the alteration of ovarian function during physiopathological
      processes.

PMID- 12219935
TI  - Steroidogenesis, proliferation and apoptosis in bovine granulosa cells: role of
      tumour necrosis factor-alpha and its possible signalling mechanisms.
AB  - This study was designed to investigate the presence of bioactive tumour necrosis
      factor-alpha (TNF-alpha) in bovine fluid collected from small (<5 mm) and large
      (>8 mm) follicles, as well as the production of the cytokine by the granulosa
      cells collected from the same type of follicles. Moreover, the effectiveness of
      10, 1 and 0.1 ng mL(-1) of human TNF-alpha (hTNF-alpha) in affecting the main
      parameters of granulosa cell function, progesterone (P4) and oestradiol-17beta
      (E2) production, cell proliferation and apoptosis, was tested. In addition, the
      study aimed to determine whether the signalling mechanisms of TNF-alpha in these
      cells involve cAMP, nitric oxide or prostaglandin E2 (PGE2) and F2alpha
      (PGF2alpha). It emerged that bioactive TNF-alpha is present in follicular fluid
      from both types of follicles and can be measured in media conditioned by
      granulosa cells from large follicles. As for the effects of hTNF-alpha, it
      inhibits P4 production in cells from both types of follicles and stimulates E2
      output in those from small follicles; it does not affect proliferation, but it
      stimulates granulosa cell apoptosis. Finally, the effects of hTNF-alpha on bovine
      granulosa cells are not mediated by nitric oxide or cAMP, as neither of these
      substances were affected by treatment with the cytokine; however, in some way,
      they could be mediated through PGE2 and PGF2alpha, the production of which was
      inhibited by TNF-alpha in cells from small follicles.

PMID- 12219936
TI  - Assessment of the immunocontraceptive effect of a zona pellucida 3 peptide
      antigen in wild mice.
AB  - Immunizing laboratory mice against a short peptide to mouse zona pellucida
      protein 3 (mZP3; amino acids 328-342) reduces fertility in some strains. This
      antigen was therefore tested to see if it is suitable for use in an
      immunocontraceptive vaccine to control wild mice. Mouse zona pellucida protein 3
      peptide conjugated to a carrier protein (keyhole limpet hemocyanin) was
      considerably more immunogenic and effective in reducing fertility in wild mice
      when compared with inbred BALB/c mice. Fertility of the immunized wild mice was
      reduced by over 50% compared with controls, whereas BALB/c mice showed no
      reduction. Variation in the responses between individual animals to mZP3 peptide
      was observed and infertility correlated to the presence of cross-reacting
      antibodies to native zona pellucida in wild, but not BALB/c, mice.

PMID- 12219937
TI  - Molecular cloning and tissue expression of the gonadotrophin-releasing hormone
      receptor in the tammar wallaby (Macropus eugenii).
AB  - Gonadotrophin-releasing hormone (GnRH) plays a pivotal role in the endocrine
      control of both reproduction and embryonic development. This first study of the
      marsupial GnRH receptor (GnRH-R) gene in the tammar wallaby provides information
      on the complex molecular events that regulate hypothalamic-pituitary-gonadal
      function in marsupials, and allows a comparison with eutherian mammals. Two
      identical wallaby GnRH-R cDNA clones were obtained, one isolated from cDNA
      generated from the testis of a 79-day-old pouch young and the other from the
      pituitary of an adult. Wallaby GnRH-R is composed of 328 amino acid residues.
      Sequence analysis showed that wallaby GnRH-R contains 7 transmembrane domains and
      is a member of the G protein-coupled receptor family. A putative protein kinase A
      phosphorylation site and a putative protein kinase C (PKC) phosphorylation site
      were found in the first intracellular loop, and an additional PKC phosphorylation
      site was located in the third intracellular loop. Comparisons with the eutherian
      GnRH-Rs show a greater diversity in the N-terminal extracellular domain. Wallaby
      GnRH-R has approximately 80% amino acid sequence homology with eutherian GnRH-Rs
      and 93% homology with the brush-tail possum, another member of the Diprotodontia
      semiorder.

PMID- 12219938
TI  - Determinants of the annual pattern of reproduction in mature male Merino and
      Suffolk sheep: modification of responses to photoperiod by an annual cycle in
      food supply.
AB  - Rams of a 'Mediterranean breed' (Merino) and a 'temperate breed' (Suffolk) were
      compared to determine how much of the differences between their reproductive
      seasons is owing to variation in their responses to photoperiodic and nutritional
      cues. In a previous study, both nutritional and photoperiodic inputs were held
      constant, and it was found that the two breeds show similar endogenous rhythms
      and, when the animals are challenged with a Mediterranean photoperiodic cycle,
      these endogenous rhythms are similarly modified. The present study tested whether
      an annual cycle in the supply of forage might modify the patterns that are
      generated by the interaction between photoperiod and endogenous rhythms. Both
      breeds were subjected to a simulated 'Mediterranean' annual cycle in photoperiod
      (10L:14D to 14D:10L) and provided with either constant food supply or a simulated
      'Mediterranean' annual cycle in food supply. In Merino rams, testicular growth
      responded to photoperiod, but nutrition dominated those responses. In Suffolk
      rams, changes in testicular size can be completely out of phase with changes in
      body mass because they are driven primarily by photoperiod, with only subtle
      responses to changes in diet. The cycle of testicular growth in the Suffolk was
      driven by changes in the secretion of gonadotrophins (follicle-stimulating
      hormone concentrations and luteinizing hormone pulse frequency). By contrast, in
      the Merino, the nutritionally driven seasonal cycle of testicular growth was
      associated primarily with changes in body mass and this relationship could not
      always be explained by changes in gonadotrophin secretion. Melatonin secretion
      was not affected by food supply. Thus, the 'Mediterranean' and 'temperate'
      genotypes have similar endogenous rhythms that are similarly modified by
      photoperiod but, with respect to seasonal changes in nutrition, they differ in
      both the nature of their reproductive response and the physiological mechanisms
      that mediate those responses.

PMID- 12219939
TI  - Damaging effects of polychlorinated biphenyls on chicken primordial germ cells.
AB  - This work describes the effects of a commercial polychlorinated biphenyl (PCB)
      mixture, Aroclor 1254, as well as 17beta-oestradiol (E2) and testosterone on
      numbers and histomorphological changes of primordial germ cells (PGCs) in gonadal
      regions of Day 5 Hyline chicken embryos. The oestrogen receptor antagonist,
      clomiphen, alone or with PCBs was used in an attempt to protect the developing
      gonad from oestrogen-like effects of chemical PCBs. The results were as follows:
      (i) PCBs delayed embryonic development independently of dose (1 microg/egg,
      P<0.05; 10 microg/egg, P<0.01; 100 microg/egg, P<0.001 v. the control) and caused
      a dose-independent increase in mortality compared with the control group (10
      microg/egg, P<0.01; 100 microg/egg, P<0.05); maximal mortality was observed in
      the 1 microg/egg group (P<0.001); (ii) PCBs decreased PGC numbers dose
      dependently (P<0.001) and caused a swollen nucleus with hyperchromatism
      (pyknosis) or cytoplasm vacuolation as signs of gonadal PGC degeneration in all
      PCB groups, or even complete disappearance in the 100 microg/egg group; (iii)
      after PCB treatment, the index of gonadal lesion increased significantly with the
      decrease of gonadal PGC number (1, 10 and 100 microg/egg, P<0.001); (iv) there
      were no observed effects of E2, testosterone and clomiphen on PGCs in the
      experiments; and (v) clomiphen failed to block the damaging effects of PCBs.
      These results suggest that the adverse effects of PCBs on chicken gonadal and
      germ cell development were initiated during the early stages of incubation
      through direct toxic effects, rather than through oestrogen-mimicking actions. As
      PGC numbers in the gonads decrease and the index of gonadal lesion increases, one
      may expect reproductive function to be compromised.

PMID- 12219940
TI  - Identification and characterization of a gene coding a novel isoform of DEAD-box
      protein.
AB  - A gene coding a novel isoform of DEAD-box protein named testicular DEAD-box
      protein (tDbp), presumably involved in testicular function, was identified and
      characterized. Testicular DEAD-box protein was cloned from a human testis cDNA
      library. The cDNA microarray hybridization showed that it was expressed at a
      higher level in adult testis than in embryo testis. Reverse transcription
      polymerase chain reaction indicated that tDbp was specifically expressed in
      testis, but not in some other tissues.

PMID- 12219941
TI  - Effects of cycloheximide treatment and interval between fusion and activation on
      in vitro development of pig nuclear transfer embryos.
AB  - The effects of cycloheximide (CHX) treatment and the interval between fusion and
      activation on the development of pig nuclear transfer (NT) embryos constructed
      with enucleated oocytes and serum-starved granulosa/cumulus cells were examined.
      One group of couplets was fused and activated simultaneously (FAS) by a single
      electrical pulse (activation pulse). Another three groups of couplets were fused
      electricaly 1.5, 2.5 or 4.5 h before being subjected to the activation pulse
      (FBA). Each group was divided into two subgroups and incubated with or without
      CHX. The NT embryos treated with CHX showed a high and stable cleavage rate,
      regardless of the interval between fusion and activation; however, development to
      blastocysts was improved only when the NT embryos were subjected to FAS with CHX.
      These results indicate that CHX-sensitive events occurring shortly after FAS may
      be responsible for the development to blastocysts. Fusion pulse rarely activated
      M II oocytes, but rapidly dropped the p34cdc2 kinase activity in NT embryos. A
      pronucleus-like structure was observed 2-2.5 h after the activation pulse with
      CHX in NT embryos of both the FAS and FBA groups. Therefore, successive
      inactivation of M-phase promoting factor and cytostatic factor at a certain short
      interval may also play an important role in the development of NT embryos.

PMID- 12219942
TI  - Angiotensin II increases intracellular calcium concentration in pig endometrial
      stromal cells through type 1 angiotensin receptors, but does not stimulate
      phospholipase C activity or prostaglandin F2alpha secretion.
AB  - Although the presence of endometrial receptors for angiotensin (Ang) II has been
      demonstrated, a specific function for AngII in the uterus has not been
      identified. Cytosolic free Ca2+ concentration [Ca2+]i, phospholipase C (PLC)
      activity and prostaglandin (PG) F2alpha secretion in response to AngII and
      oxytocin (OT) were measured in pig endometrial stromal cells collected 16 days
      after oestrus. Treatment with 100 nM OT or AngII increased (P<0.001) [Ca2+]i in
      stromal cells similarly (720 +/- 34 v. 690 +/- 33 pM, respectively). Subsequent
      administration of OT or AngII to the same cells induced smaller [Ca2+]i increases
      (25% or 35% of the initial responses, respectively) that occurred only if the
      second exposure to the same agent took place at least 5 min after the first. When
      administered sequentially, OT and AngII each induced a full response within 1 min
      of the previous treatment, regardless of which peptide was applied first. Whereas
      OT increased PLC activity and PGF2alpha secretion in stromal cells (P<0.01),
      AngII did not increase either PLC activity or PGF2alpha secretion. Type I AngII
      (AT1) receptors were present on stromal cells, whereas AT2 receptors were absent.
      Therefore, the effect of AngII in stromal cells was mediated via AT1 receptors.
      That AngII increased [Ca2+]i in stromal cells, but did not increase PLC or
      PGF2alpha secretion, indicates that either AngII releases a pool of Ca2+ through
      a mechanism that is not mediated by PLC and is not involved in PGF2alpha
      secretion or that a mechanism for PGF2alpha production other than one involving
      Ca2+ may exist.

PMID- 12219943
TI  - Seasonal differences in lamb birthweight do not arise from inherent differences
      in the oocyte and/or early embryo.
AB  - The aim of this study was to determine whether previously observed seasonal
      differences in conceptus development in ewes are attributable to inherent
      differences in the oocyte and/or early embryo. Day 6 embryos were recovered from
      50 ewes subjected to a standard oestrus synchronization, superovulation and
      laparoscopic artificial insemination protocol during October (peak breeding
      season) and April (transition to anoestrus). During the following October, 40
      grade 1 and 2 embryos from each month, which had been cryopreserved at the late
      morula or unexpanded blastocyst stage, were thawed and transferred in singleton
      to synchronous recipients. Resulting pregnancies were monitored to term. For ewes
      receiving October- and April-produced embryos, overall mean +/- SEM liveweight at
      the time of embryo transfer was 72 +/- 0.7 kg, body condition score was 3.1 +/-
      0.04 units, and the number of corpora lutea on the ovaries was 2.7 +/- 0.11 per
      ewe. Thirty-one and 27 ewes, respectively, became pregnant and their gestation
      lengths were 147 +/- 0.2 and 147 +/- 0.3 days. There was no effect of month of
      embryo production on peripheral ovine pregnancy-associated glycoprotein
      concentrations during pregnancy or on fetal and placental characteristics at
      term, but, for each month, male lambs were heavier than females and were
      associated with larger placentae. Lamb birthweight was positively correlated with
      placental weight (r2 = 0.474, P<0.001) and the total weight of cotyledonary
      tissue (r2 = 0.429, P<0.001), but not to the number of cotyledons. Results
      demonstrate close relationships between fetal and placental weights at term, and
      that seasonal effects on conceptus development in ewes do not arise from inherent
      differences in the oocyte and/or early embryo.

PMID- 12219944
TI  - Porcine zonae pellucidae immunization of tammar wallabies (Macropus eugenii):
      fertility and immune responses.
AB  - This study looked at the feasibility of targeting the zona pellucida for a
      contraceptive vaccine as a possible alternative method of control for
      overabundant macropods. Tammar wallabies, as a model for other macropods, were
      immunized with porcine zonae pellucidae (PZP) and were found to achieve
      significant concentrations of antibody to PZP in sera and reproductive tract
      fluids. Wallabies immunized with PZP exhibited lower ovarian weight with reduced
      numbers of antral follicles when compared with control animals. Wallabies were
      placed in a natural mating trial followed by an artificial insemination trial.
      None of the PZP-immunized wallabies produced offspring in the natural mating
      trial compared with 67% of control animals. To further assess fertility, a sub
      sample of the wallabies were superovulated and artificially inseminated. This
      resulted in all control wallabies producing fertilized ova and all PZP-immunized
      wallabies failing to ovulate. These results suggest that immunocontraception
      based on targeting antigens of the zona pellucida may be an effective strategy
      for fertility reduction in macropods.

PMID- 12219945
TI  - Capacitation-like changes in equine spermatozoa throughout the cryopreservation
      process.
AB  - Chlortetracycline (CTC) fluorescence staining analysis was used to investigate
      cryopreservation-induced capacitation-like changes in equine spermatozoa. Freshly
      ejaculated spermatozoa were found to display a high proportion of F pattern cells
      (uncapacitated; 93.6%) and a lower proportion of B pattern (capacitated; 5.4%)
      and AR pattern (acrosome-reacted; 1%) cells. Following cryopreservation in
      modified Kenney's medium, capacitation-like changes were observed. There was a
      significant increase in the proportion of spermatozoa displaying the B pattern
      (64.8%; P<0.001) and AR pattern (32.8%; P<0.001), with a corresponding decrease
      in the proportion of spermatozoa displaying the F staining pattern (2.5%;
      P<0.001). Further analysis of CTC fluorescence staining patterns showed that
      there was a major decrease in the proportion of F pattern spermatozoa
      corresponding to an increase in B pattern spermatozoa following removal of
      seminal plasma after centrifugation and resuspension in freezing medium. There
      was a further decline in the proportion of F pattern spermatozoa, corresponding
      to increases in B and AR pattern spermatozoa, after the freezing and thawing
      steps. Resuspension of centrifuged spermatozoa in homologous seminal plasma did
      not induce capacitation-like changes. These data indicate that the process of
      freezing and thawing stallion semen induces capacitation-like changes in
      spermatozoa and that most of the change is brought about by removal of seminal
      plasma, with further changes induced by the actual freezing and thawing step.

PMID- 12219946
TI  - Comparison of gene expression at the feto-maternal interface between normal and
      recurrent pregnancy loss patients.
AB  - Normal pregnancy requires a series of immunological, metabolic, vascular and
      endocrine regulating processes. However, the specific genes and proteins involved
      in these processes are not well defined. Aberration of these processes may lead
      to problems in pregnancy. One of these problems may be recurrent pregnancy loss
      (RPL). Little information is available on the level of expression of genes that
      may play a role in normal pregnancy. Therefore, this study determined whether
      different levels of gene expression at the feto-maternal interface could be
      associated with factors for RPL. The expression patterns of genes isolated from
      subtractive hybridization analysis performed with chorionic villi from normal and
      abnormal pregnancies were investigated. Eight genes classified into groups,
      including immunosuppression-related, embryo attachment-related and angiogenesis
      related, were isolated.

PMID- 12219947
TI  - Immunolocalization of sex steroid hormone receptors in the canine uterine tube
      and their relation to sex steroid hormone concentrations.
AB  - The aim of this immunohistochemical study was to describe the cellular
      distribution of the estrogen receptor-alpha (ERalpha), progesterone receptor (PR)
      and androgen receptor (AR) in canine uterine tubes. Samples of uterine tubes were
      taken from dogs in different stages of the estrous cycle, and dogs that were
      pregnant or had just delivered. Nuclear staining for sex steroid hormone
      receptors was observed in the surface epithelium, stromal cells and smooth muscle
      cells of the muscular layer. Only slight differences in staining pattern were
      observed between the ampulla and fimbriae. The staining for ERalpha and PR showed
      changes throughout the estrous cycle. Some of these changes were related to
      changing concentrations of sex steroid hormones. High staining scores for ERalpha
      and PR were found during proestrus and low scores during early metestrus. The
      staining for AR showed only minor cyclic changes. However, during proestrus and
      estrus, cytoplasmic staining for AR was observed in differentiated secretory
      epithelial cells, when nuclear staining in these cells was nearly absent. For the
      three hormone receptors, stromal cells generally stained with a higher intensity
      than epithelial cells. It is likely that many steroid hormone actions on the
      epithelium are mediated through stromal cells. During pregnancy, rather high
      staining scores were found for ERalpha and AR in the uterine tube. This is in
      contrast to observations in the canine pregnant uterus.

PMID- 12219949
TI  - Healthcare ethics needs to be revisited, revisioned and revitalized.

PMID- 12219948
TI  - Immunolocalization of sex steroid hormone receptors in canine vaginal and vulvar
      tissue and their relation to sex steroid hormone concentrations.
AB  - The aim of this immunohistochemical study was to describe the cellular
      distribution of the estrogen receptor-alpha (ERalpha), progesterone receptor (PR)
      and androgen receptor (AR) in canine vaginal and vulvar tissue. Samples were
      taken from dogs in different stages of the estrous cycle. Nuclear staining for
      ERalpha, PR and AR was observed in surface epithelium, stromal and smooth muscle
      cells. Receptors were also expressed in vulvar skin. Cytoplasmic staining for AR
      was observed in basal and parabasal cell layers of vulvar and vaginal epithelium.
      For all three receptors, staining intensity was generally higher in stromal cells
      compared with epithelial cells, suggesting that stromal cells may be more
      receptive to steroid hormone action. Therefore, as in other tissues of the female
      genital tract, stromal-epithelial interactions induced by sex steroid hormones
      may be of importance in canine vaginal and vulvar tissues. No cyclic changes in
      receptor immunostaining were observed. Significant positive correlations were
      found between receptor immunostaining in some vaginal and vulvar cell groups and
      the serum concentrations of estradiol-17beta and testosterone, but not with the
      serum progesterone concentration. Significant negative correlations were found
      between ERalpha immunostaining in epithelial and stromal cells of the vagina and
      the serum estradiol-17beta concentration, suggesting a negative feedback
      mechanism between estradiol-17beta and its receptor. Both cell types play a role
      in the differentiation of vaginal epithelium, under the influence of estradiol
      17beta.

PMID- 12219950
TI  - The changing focus of health care ethics: implications for health care
      professionals.
AB  - Contemporary health care ethics has become preoccupied with the issue of people's
      rights to and in health care (eg the rights to informed consent, confidentiality,
      quality of life, death with dignity, etc). There is no question that this
      preoccupation has achieved some morally significant and beneficial outcomes in
      health care domains. Nevertheless, it is evident that health care ethics has not
      achieved its most basic task, namely, to promote and protect the genuine
      wellbeing and welfare interests of those who are among the most vulnerable people
      in society and whose health status is at risk. A key contention of this paper is
      that if health professionals are going to be able to meet future moral challenges
      posed by the complex question of human health, then the nature, aims, purpose,
      significance, and modus operandi of contemporary health th care ethics needs to
      be revisited, re-visioned, and revitalised.

PMID- 12219951
TI  - Providing residential care to older Australians: issues for registered nurses.
AB  - Contemporary nursing in residential aged care facilities poses many challenges.
      Issues impacting on registered nurses providing care to older Australians living
      in residential aged care settings are explored and described in this paper. Five
      broad themes emerged from the analysis of thirty interviews with Registered
      Nurses, eleven focus groups with participants who worked with registered nurses
      in the residential aged care facilities selected in the sample, and five nominal
      groups which consisted of key stakeholders from the aged care industry and
      professional nursing forums. These themes were: a changing and increasingly
      complex role; perceptions of the registered nurse in residential aged care and
      how to deal with them; the need for strategies to work with others; coping with
      the everyday demands; and dealing with a sense of powerlessness and lack of
      control. The identified themes form the basis of the discussion to follow.

PMID- 12219952
TI  - Exploring the therapeutic potential of friendliness and friendship in nurse
      client relationships.
AB  - Friendliness and friendship, within the nurse-client relationship, are explored.
      Friendliness is superficial and includes nurses' smiling, joking, a warm tone of
      voice and interest in clients, while friendship is a deeper more affective
      involvement between client and nurse. The therapeutic outcomes of friendliness
      and friendship are significant. When nurses are friendly, client feelings of
      disease, strangeness and alienation are replaced by feelings of comfort,
      belonging and involvement. Friendship between nurse and client has similar
      outcomes but is a deeper experience that is simultaneously rewarding and
      sustaining for both. The therapeutic potential of friendliness and friendship
      suggests: (1) focused research would assist nursings' understanding of these
      concepts, and (2) determine their implications to nurse education and practice.

PMID- 12219953
TI  - Participatory research in breast cancer: a case study in regional Victoria.
AB  - While participatory research is now strongly advocated as progressive, ethical
      and useful, consultation with participants and other stakeholders can raise
      issues which compromise research or which create conflicting choices in research
      protocols. This paper discusses some of the issues raised by a participatory
      research project undertaken to assess the needs of women with breast cancer in
      northern Victoria. The participatory process has meant that despite some
      compromises, there were positive outcomes from the research process that would
      not have otherwise been achieved.

PMID- 12219954
TI  - A review of mentoring in education: some lessons for nursing.
AB  - The mentoring relationship has been described as an invaluable learning activity
      for beginners as well as experienced practitioners such as teachers,
      administrators, nurses, managers, and other professionals. In an attempt to
      identify key outcomes of mentoring for the parties concerned, this paper examined
      some of the salient research literature on mentoring taken from the discipline of
      education. We drew upon the findings of a structured review, in which 159 pieces
      of empirical literature on mentoring in educational settings was examined. This
      paper reviews the positive and negative outcomes of mentoring for the mentor and
      protege/mentee. Discussion of the findings as well as some important implications
      for those charged with planning mentoring programs in nursing are outlined.

PMID- 12219955
TI  - Role ambiguity in nursing: undergraduate students' struggle for direction.
AB  - An experience common to many undergraduate nursing students, particularly whilst
      on placement in the clinical area, is a sense of aimlessness, lack of direction
      and standard role, and an overall ambiguity about what nursing is and does.
      Research in the nursing literature contributes to and supports the concept of the
      lack of clarity of the nursing role. Whilst the discourse of nursing is diverse
      and covers many aspects of nursing, a number of core issues may be seen to
      emerge. These contribute to form a concept that may be identified as the
      ambiguity of nursing. This paper identifies those issues and represents this
      concept of role ambiguity. These issues include the concept of caring and the
      apparent lack of clarity over what this actually is in a nursing context.

PMID- 12219956
TI  - Third-space fluid shift in elderly patients undergoing gastrointestinal surgery:
      Part 1: Pathophysiological mechanisms.
AB  - Third-space fluid shift, the movement of body fluid to a non-functional space, is
      a frequently occurring and potentially fatal clinical phenomenon. Little
      published research exists however in medical or nursing journals concerning its
      incidence, significance and ramifications in elderly patients undergoing major
      gastrointestinal surgery. This initial article, part I, explores fluid movement
      between fluid compartments and uses these principles to discuss the
      pathophysiology of the two distinct phases of third-space fluid shift. Part II
      will examine the criteria nurses could use in the clinical assessment of patients
      in both first and second phases third-space fluid shift and discuss the clinical
      reliability of these criteria.

PMID- 12219957
TI  - Difference still troubles university environments: emotional health issues
      associated with lesbian visibility in nursing schools.
AB  - This article addresses some of the findings from a study, which investigated the
      lived experiences of women nurse academics in Australia, New Zealand, the United
      States of America and the United Kingdom. Specifically, this article reports on
      the findings of the experiences of lesbian nurse academics in the study. There
      were 15 lesbians who participated in this research. The results revealed that
      lesbian nurse academics are experiencing homophobia and as a consequence were
      suffering emotional health effects. Emotional health disruptions were
      irrespective of whether they were 'visible invisible' regarding their sexuality.

PMID- 12219958
TI  - A study of female nurses combining partner and parent roles with working a
      continuous three-shift roster: the impact on sleep, fatigue and stress.
AB  - This study of female nurses working a continuous 3-shift roster found that the
      average sleep duration per 24-hours across the roster is almost one hour less for
      nurses who combine shiftwork, partner and parent roles. In particular, they are
      not free to use the later starting afternoon shift as an opportunity to repay the
      sleep debt incurred on night shift. The results show an interaction between work
      and family roles resulting in chronic fatigue that is a risk factor especially
      when combined with the acute fatigue associated with night work. The sleep record
      data is supported by interview data which highlight shiftwork as a stressor that
      reduces the opportunity for participation in social and leisure activities by all
      three of the groups studied: single, partnered and partnered with children. The
      strain of shiftwork on personal and social relationships reduces the resources
      available for coping with the emotional and physical stressors encountered by
      nurses in their work and family roles.

PMID- 12219959
TI  - Emerging alternatives to allogeneic blood transfusions.

PMID- 12219960
TI  - Autologous transfusion in surgical patients at Kenyatta National Hospital,
      Nairobi.
AB  - OBJECTIVE: To identify autotransfusion strategies and their basis in elective
      surgery patients. DESIGN: A cross sectional prospective study. SETTING: General
      surgery and orthopaedic wards, Kenyatta National Hospital, Nairobi. SUBJECTS:
      Adult patients of both sexes planned for elective surgery. MAIN OUTCOME MEASURE:
      Forevery patient, the following were enquired about and documented: age in years,
      sex, ethnicity, religion, occupation and educational standard. Blood values of
      haemoglobin, platelet counts, total and differential white cell counts, urea,
      electrolytes and liver function tests were assayed. Others were the number of
      units of blood donated before the operation, the type of surgery performed, time
      taken from diagnosis to performing the operation and whether the blood was
      transfused preoperatively, intraoperatively and postoperatively. RESULTS: A total
      of sixty three cases constituting five per cent of all surgical patients admitted
      during the period of study were evaluated. Of these 53 (84%) were males and ten
      (16%) females. The age range was 15 to 65 years with a peak at 45-49 years. There
      were more Christians (90%) than Muslims (10%). In all, 32 (51.6%) had primary
      school education, 23 (36.5%) secondary school education, seven (11.3%) no formal
      education and one (1.6%) had attained college level. Employment pattern showed
      50% were civil servants, 30% were self employed and 20% were unemployed. The
      duration of disease ranged from 1-24 weeks with two peaks at two weeks and six
      weeks. Orthopaedic cases constituted 78.7% and general surgery 21.3%.
      Preoperative haemoglobin ranged from 13.5-14.2 g/dl. Transfusions were given
      intraoperatively to 41 (66.1%) and to 12 (33.9%) postoperatively. Mean duration
      of hospitalisation was 13 days (range 5 to 21 days). 98.4% deposited only one
      unit while 1.6% deposited four units of blood. Only one patient required
      additional transfusion from homologous donors. CONCLUSION: The strategies and
      basis for autotransfusion have been demonstrated among a majority of adult
      patients requiring orthopaedic procedures. Major determinants are shown to be
      baseline blood count profiles and time to operation.

PMID- 12219962
TI  - Salmonella, Shigella and growth potential of other food-borne pathogens in
      Ethiopian street vended foods.
AB  - OBJECTIVE: To evaluate the bacteriological safety of food items sold by street
      vendors with regard to Salmonella and Shigella and to assess the growth potential
      of some foodborne pathogens in some street foods. DESIGN: Collection of street
      vended foods and laboratory based microbiological analysis. SETTING: Microbiology
      Laboratory, Department of Biology, Addis Ababa University, Addis Ababa, Ethiopia.
      RESULTS: Most of the street food samples had aerobic mesophilic counts >10(7)
      cfu/g. Nine "kitfo" and one "egg sandwich" samples yielded Salmonella. Shigella
      was isolated from three "macaroni" samples. The Salmonella isolates were
      sensitive to all ten drugs tested but the Shigella isolates had multiple
      resistance against five drugs. In a challenge study, Salmonella typhimurium,
      Shigella flexneri and Staphylococcus aureus grew in street-vended food samples to
      hazardous levels within eight to twelve hours. CONCLUSION: Street foods are
      heavily contaminated with micro-organisms and are potential sources of food borne
      infections. Health hazards from street foods may be significantly minimised by
      consumption within four hours of preparation.

PMID- 12219961
TI  - Nutritional rickets in young Nigerian children in the Sahel savanna.
AB  - OBJECTIVES: To determine the prevalence of clinical and biochemical rickets in an
      under-five out-patient population, relate the prevalence of biochemical rickets
      (BR) to the sociocultural characteristics of families and determine the response
      of nutritional rickets to vitamin D therapy. DESIGN: Prospective cross-sectional
      and retrospective case-series surveys. SETTING: Paediatric general out-patient
      and consultant clinics. SUBJECTS: One hundred and ninety eight out-patients and
      twenty two patients aged >1 to 60 months treated for nutritional rickets.
      INTERVENTIONS: Clinical examination, interview with mothers and determination of
      biochemical abnormalities of under-fives and management of patients with rickets
      using stosstherapy. MAIN OUTCOME MEASURES: Prevalence of BR and response to
      stosstherapy. RESULTS: Eight (4%) patients in the survey had clinical and
      biochemical rickets while 33 (17%) had biochemical rickets only; 92 (47%) other
      patients had isolated hypocalcaemia and/or hypophosphataemia. The prevalence of
      BR was higher in males (p <0.05), and increased with age (p <0.001). The
      prevalence was lower in families who were indigenous to the area (p <0.05),
      children of Moslem families (p <0.05) and children whose mothers were full-time
      housewives, unskilled or traders (p <0.01), and who lacked any formal western
      education (p = 0.157). Three of the seven evaluable patients who received
      stosstherapy responded late. CONCLUSION: The results support the hypothesis that
      deficiency or reduced availability of dietary calcium may be of at least equal
      importance with vitamin D deficiency in the aetiology of nutritional rickets in
      the Sahel savanna.

PMID- 12219963
TI  - Lower genital tract infections among pregnant women: a review.
AB  - OBJECTIVES: To determine the prevalence of lower genital tract infections,
      discuss briefly common maternal foetal complications associated with them and
      assess the usefulness of diagnostic algorithms in their management among pregnant
      women in the developing countries. DATA SOURCE: Articles published in English
      language since 1987 were looked through MEDLINE and OVID using key words
      supplemented by manual search in libraries except when full text of a subject was
      accessible via internet. STUDY SELECTION: Original and review articles addressing
      genital tract infections, associated complications and diagnostic evaluation in
      pregnant women were included. Emphasis was given to articles reported from
      developing countries. DATA EXTRACTION: A total of thirty five articles were
      retrieved and reviewed for information on the performance of diagnostic
      algorithms, prevalence rates and adverse maternal-foetal effects of lower genital
      tract infections in pregnancy. DATA SYNTHESIS: Lower genital tract infections are
      very common among apparently healthy looking pregnant women with an overall
      prevalence of 40-54%. Specific pathogens that were isolated from the vagina
      and/or cervix of asymptomatic pregnant women include: C. albicans (14-42%), T.
      vaginalis (11-20%), C. trachomatis (7-31%), N. gonorrhoea (0.5-14%) and group B
      streptococcus (4-25%). Untreated, genital tract infections in pregnant women may
      result in: foetal loss, preterm labour, preterm birth, premature rupture of the
      membranes, low birthweight, eye and lung damage in the newborn. Although the
      feasibility is good, the performance of clinical algorithms in the evaluation and
      management of lower genital tract infections is worse in pregnant women and
      better results are achieved for vaginal infections than cervical infections.
      CONCLUSION: Routine screening for clinically important pathogens should be
      considered during antenatal service. There is a need to develop simple, cheap and
      reliable laboratory tests and better clinical algorithms for the diagnosis of
      reproductive tract infections among pregnant women.

PMID- 12219964
TI  - Possible immunological basis for recurrent spontaneous abortions: a review.
AB  - BACKGROUND: In normal pregnancy, the pregnant mother paradoxically tolerates the
      semi-allogeneic foetus until term. Experimental and clinical data to explain such
      tolerance in man reflects the involvement of multiple mechanisms. OBJECTIVE: To
      review the data pertaining to the experimental and clinical efforts to explain
      why the mother immunologically tolerates a semi-allogeneic pregnancy to term.
      DESIGN, SETTING AND METHODS: A review of the literature on state of the art
      thinking among researchers and clinicians on recurrent spontaneous abortions is
      summarised. RESULTS: A large body of recently published data strongly suggest
      that a breakdown in immunological maternal-foetal interactions may lead to
      occasional or recurrent foetal loss. Immunoregulatory activities involving
      blocking antibodies, regulatory factors, immunological cells, hormones,
      structural proteins and cytokines constitute the pregnancy-sustaining network.
      CONCLUSION: The majority of the evidence reviewed points to the involvement of
      immunological factors in successful pregnancies. However, the underlying
      mechanisms are inadequately explained, are largely speculative and require more
      focused investigation. A complete understanding of the mechanisms involved would
      enhance our capacity to develop rational ways of addressing recurrent pregnancy
      losses.

PMID- 12219965
TI  - Determinants of immunisation coverage among children in Mathare Valley, Nairobi.
AB  - OBJECTIVE: To establish the factors that determine the levels of immunisation
      coverage among children under five years in Mathare Valley. DESIGN: A cross
      sectional study describing the situation at a point in time. SETTING: Mathare
      Valley slum with a population of 50,000 people in the city of Nairobi. SUBJECTS:
      The study population was mothers with children under five years in Mathare Valley
      and had been resident there for a period not less than five years prior to the
      study. OUTCOME MEASURES: Level of immunisation coverage among children in the
      study population and the factors that contribute to the low immunisation
      coverage. RESULTS: Knowledge on immunisation was high with 90% of the respondents
      able to define immunisation. The attitude on immunisation was positive (74.4%)
      and immunisation coverage stood at 62.2%. Age, level of education, attitude and
      knowledge on immunisation among the residents were significant determinants of
      immunisation coverage. CONCLUSION: Immunisation coverage was lower than the
      national average in Mathare Valley. Advanced mother's age, low level of education
      and relative lack of knowledge on immunisation were responsible for the low
      coverage.

PMID- 12219966
TI  - Lymphatic filariasis in kenya since 1910, and the prospects for its elimination:
      a review.
AB  - OBJECTIVES: To provide an overview of lymphatic filiariasis in Kenya from the
      first time its prevalence was reported to the present day, with suggestions of
      issues that are yet to be resolved and to present the prospects for its
      elimination. DATA SOURCES: Published and unpublished reports on filariasis
      studies in Kenya. STUDY SELECTION: Field-based epidemiological studies covering
      aspects of clinical, parasitology, entomology, social, economic, diagnosis and
      control of filariasis. DATA EXTRACTION: Review of published articles in
      scientific journals and communications, retrieval and review of published
      scientific articles from the Internet and personal communications. DATA
      SYNTHESIS: Re-organisation and pooling retrieved published data. CONCLUSIONS:
      Almost one century after the first documented report of lymphatic filariasis in
      Kenya, no National Control Programme has been instituted. However, important
      findings that have implications on its control have been made and they should be
      utilised to implement a National Control Programme. On implementation of the
      National Control Programme, research should be focussed on the remaining
      unresolved issues and conducted within the framework of the Programme. The World
      Health Organisation has targeted lymphatic filariasis for global elimination by
      the year 2020. Kenya is well positioned to formulate her National Plan for
      Elimination of Lymphatic Filariasis (NPELF) and join other endemic countries
      worldwide, which have already launched their plans, in the global efforts to
      eliminate lymphatic filariasis as a public health problem.

PMID- 12219967
TI  - Collagen Ialpha1 and vitamin D receptor gene polymorphisms in South African
      whites, blacks and Indians.
AB  - OBJECTIVE: To determine whether polymorphic differences exist between black,
      white and Indian South Africans in genes associated with bone mineral density and
      osteoporosis. DESIGN: Genes selected were the vitamin D receptor (Apa I and Taq I
      polymorphisms) and collagen (Sp I transcription factor polymorphism) using
      standard molecular biology techniques. SETTING: Department of Chemical Pathology,
      Nelson R Mandela School of Medicine, University of Natal, Durban, South Africa.
      SUBJECTS: Healthy male and female blood donors living in the Durban metropolitan
      region, South Africa. The group comprised black Africans (n=264), white
      Caucasians (n=247) and Asians of Indian origin (n=194). RESULTS: No significant
      differences in genotypes were seen between white and Indian subjects. Blacks had
      a significantly higher frequency of the TT Taq I genotype and a significantly
      lower frequency of the Ss Sp I genotype. No ss genotype was detected in blacks.
      CONCLUSION: The very low frequency of the collagen Sp I s allele and higher
      frequency of the VDR T allele in blacks may be associated with the lower
      incidence of osteoporosis in this ethnic group.

PMID- 12219968
TI  - Electrocardiographic findings in Ethiopians on pentavalent antimony therapy for
      visceral leishmaniasis.
AB  - BACKGROUND: The old short course regimens of pentavalent antimonial (sb(v))
      therapy of visceral leishmaniasis (VL) have largely been abandoned worldwide as
      they are associated with increasing problems of relapse and unresponsiveness. In
      Ethiopia, some hospitals still use the old interrupted and short course regimen
      partly because of fear of drug toxicity. OBJECTIVE: To evaluate the safety of the
      WHO recommended uninterrupted therapy at a dose of 20 mg sb(v)/kg for up to
      thirty days. DESIGN: A prospective study. SETTING: Patients were recruited from
      Addis Ababa hospitals and from Konso VL endemic area in southern Ethiopia.
      SUBJECTS: Forty nine patients who included, ten HIV-positive and 39 HIV-negative,
      were enrolled for the study. RESULTS: Twenty three HIV-negative patients got
      treatment for 20 days and the rest, 16 HIV-negative and 10 HIV-positive, were
      treated for 28 to 30 days. Among HIV-seronegatives, the mean QT interval
      corrected for heart rate (QTc) at the end of therapy in patients treated for 20
      days and 28-30 days was comparable (0.419 +/- 0.031 seconds versus 0.424 +/-
      0.027 seconds, respectively). Among patients treated for 28-30 days, the mean QTc
      in HIV co-infected patients was comparable to that of HIV-negatives (0.416 +/-
      0.018 seconds versus 0.424 +/- 0.027). Comparable rates of new ECG changes
      involving the T waves were observed in two HIV-positive (20%) and two HIV
      negative (12.5%) patients treated for 28-30 days, and in seven (30.4%) HIV
      negative patients treated for 20 days. Overall, only two (4.1%) patients (all HIV
      negative males) had QTc interval > or = 0.50 seconds at the end of therapy. In
      one patient, the prolonged QTc was noted on the twentieth day with bradycardia of
      44/minute. CONCLUSIONS: In Ethiopian VL patients with normal renal function,
      sb(v) therapy at a daily dose of 20 mg/kg for up to 30 days is safe and only
      rarely associated with clinically significant bradycardia which resolves after
      temporary cessation of therapy. Furthermore, in areas with limited facilities,
      monitoring the pulse rate during antimonial therapy may help detect impending
      cardiotoxicity.

PMID- 12219969
TI  - Lateral asymmetry in grip strength: utility of the ten per cent rule.
AB  - OBJECTIVE: To measure asymmetry in grip strength between hands in left, right and
      mixed handers and to test utility of the ten per cent rule. DESIGN: A cross
      sectional study. SETTING: Queen Elizabeth Central Hospital, Blantyre, Malawi.
      SUBJECTS: One hundred and seventy six healthy volunteers (102 males and 74
      females) aged 15 to 66 years were selected from visitors to the patients admitted
      at the hospital. MAIN OUTCOME MEASURES: Bilateral measurements of maximal grip
      strength, assessment of handedness using a questionnaire incorporating questions
      on hand preferred for six habitual activities. RESULTS: In about 70% of males and
      females, the right hand was stronger than the left hand while frequency of left,
      mixed, and right handers was 5.7%, 4.5% and 89.2%, respectively. Significant
      association (chi2 = 6.43, n = 2, p<0.05) was found between handedness and
      stronger hand with preferred hand being stronger in most subjects. However, for
      about 40% of left and mixed handers and 27% of right handers, the non-preferred
      hand was stronger. The mean differences between grip strengths varied between 10%
      and 20% in different categories of handers when stronger hand was taken into
      consideration. Without considering the stronger hand, the mean bilateral
      difference in maximal grip strength in the three categories of handedness was
      between three and six per cent.. CONCLUSION: Distinction between stronger hand
      and hand preferred for skilled activities should be made and considered when
      assessing limitations in hand strength in clinical practice.

PMID- 12219970
TI  - Fractures of the mandible in children.
AB  - OBJECTIVE: To determine the pattern of occurrence of mandibular fractures in a
      paediatric population. DESIGN: A retrospective study. SETTING: University College
      Hospital, Ibadan, Nigeria. SUBJECTS: Seventy two paediatric patients seen and
      managed between 1989 and 1998. RESULTS: Road traffic accidents were the most
      common (52.8%) cause of mandibular fractures. The majority of the patients
      (57.0%) were within the age group (12-16 years). The body of the mandible was
      involved in 43.4% of the fractures. Eyelet wires with intermaxillary fixation was
      used in 41.7% of the cases. CONCLUSION: There is a need to enforce legislation
      aimed at preventing road traffic accidents to reduce maxillofacial injuries among
      children.

PMID- 12219971
TI  - Gastrointestinal obstruction from phytobezoar in childhood: report of two cases.
AB  - This is a report of two children aged twenty seven months and six years
      respectively presenting with gastrointestinal obstruction from phytobezoar. In
      the 27-month old child, laparotomy and gastrotomy was performed to evacuate the
      bezoar. However, death occurred from hypokalaemia. The six-year old child had a
      sacro-abdomino-perineal pull through for anorectal malformation previously and
      the bezoar lodged just above the neoanus. Neoanal dilatation allowed removal of
      the bezoar and relief of the obstruction. There has been no recurrence. The
      literature on bezoar is briefly reviewed.

PMID- 12219972
TI  - Pathological changes in juvenile Atlantic halibut Hippoglossus hippoglossus
      persistently infected with nodavirus.
AB  - This is the first description of a persistent subclinical nodavirus infection in
      the Atlantic halibut Hippoglossus hippoglossus. Juvenile fish (1 to 5 g) were
      sampled at 4, 5 and 8 mo of age at a fish farm in Norway during and after
      weaning. None showed clinical signs of viral encephalopathy and retinopathy (VER)
      or other disease. Pathological changes and/or nodavirus were detected by light
      microscopy, immunohistochemistry, reverse transcriptase polymerase chain reaction
      (RT-PCR) and transmission electron microscopy in all fish examined. High numbers
      of virus particles were found in macrophage-like cells in the central nervous
      system, including brain and retina (CNS). The virus particles displayed the
      icosahedral shape and size (approximately 25 nm) characteristic of nodaviruses.
      The virus-infected cells formed focal cell aggregates and were seen in all
      regions of the brain and all nuclear cell layers of the retina. The cytoplasm of
      the infected cells was filled with membrane-enclosed inclusions packed with virus
      particles. Some virus particles lay along membranes and formed membrane-bound
      necklace-like arrangements. The virus-infected cells of the retina also contained
      pigment granula located generally inside virus inclusions and sometimes forming a
      coating around the virus particles. All frontal parts with the eyes and brain and
      50% of the mid-parts, which included the abdominal organs, were found positive
      for nodavirus with RT-PCR. Pathological changes in these persistently nodavirus
      infected fish differ from earlier descriptions in Atlantic halibut during
      outbreaks of VER. Vertical transmission from infected spawners is believed to be
      a major route for nodavirus infection. Detection of nodavirus in subclinical
      infected fish and a better understanding of its pathogenesis are important in
      order to prevent the spread of nodavirus in the fish-farming industry.

PMID- 12219973
TI  - Isolation of viral hemorrhagic septicemia virus from Greenland halibut
      Reinhardtius hippoglossoides caught at the Flemish Cap.
AB  - Viral hemorrhagic septicemia virus (VHSV) was isolated from apparently healthy
      Greenland halibut Reinhardtius hippoglossoides caught in the Flemish Cap, a deep
      fishing ground in the North Atlantic Ocean in international waters near
      Newfoundland. The identity of the virus was confirmed by electron microscopy,
      immunodot, seroneutralization and reverse transcriptasepolymerase chain reaction.
      In the serology assays, all isolates reacted in the immunodot assay with a
      polyclonal antiserum against the European VHSV Type Strain F1, and were
      neutralized by the same antiserum, although most of the strains showed low or
      moderate neutralization titers. None of the isolates were detected by
      immunofluorescence using a specific monoclonal antibody against a nucleocapsid
      related protein of VHSV F1. This is the first report of VHSV isolated from wild
      Greenland halibut, which represents a new host species for the virus, and it is
      also the first evidence of VHSV in a location close to the Atlantic coast of
      North America. This isolation indicates that VHSV is more widely distributed than
      has been thought, and appears to support a marine origin of this virus.

PMID- 12219974
TI  - Spatial and temporal variation in Anguillicola crassus counts: results of a 4
      year survey of eels in Mediterranean lagoons.
AB  - We present the results of a survey of anguillicolosis in the Rh6ne River delta.
      From January 1997 to December 2000, a total of 13,319 eels (Anguilla anguilla
      from elver to silver phase) were examined, in which we found 22,227 swimbladder
      nematodes (Anguillicola crassus adults and pre-adults). A generalised linear
      model (GLM) framework was used to explore the relative contribution of various
      factors to the occurrence, intensity and abundance of the parasite. We reveal a
      major influence of the month of sampling, and we document the existence of a
      seasonal pattern with regular peaks in early summer and late winter. In contrast,
      the year of sampling is of secondary importance, and no particular trend in the
      development of the infection can be detected. More than a decade after the first
      record of A. crassus in the Rhjne River delta, anguillicolosis has thus attained
      a constant infection rate of nearly 50%, with a mean number of 3 or 4 macroscopic
      lumen worms per infected eel. The eel length strongly influences the intensity
      and the abundance of the nematode, but has little if any effect on the
      probability of being infected. There exists a linear relationship between eel
      size and the number of parasites, but not between eel size and prevalence. We
      observe a decrease in the proportion of infected individuals among elver eels. We
      discuss this result in relation to the possible mortality of heavily infected
      individuals and/or a change in the eels' alimentary diet.

PMID- 12219975
TI  - Effect of nitrite on interaction between the giant freshwater prawn Macrobrachium
      rosenbergii and its pathogen Lactococcus garvieae.
AB  - Addition of nitrite-N at 1.5 mg l(-1) in tryptic soy broth (TSB) significantly (p
      < 0.05) decreased the growth rate of the bacterial pathogen Lactococcus garvieae
      and significantly (p < 0.05) reduced mortality compared to zero nitrite controls
      when injected into giant freshwater prawns Macrobrachium rosenbergii at 5 x 10(5)
      colony-forming units (CFU) per prawn. In other experiments, whereby prawns were
      injected with TSB-grown L. garvieae (5 x 10(5) CFU prawn(-1)) and then held in
      water containing nitrite-N, mortality at 72 h post-injection was significantly (p
      < 0.05) higher for prawns held in water containing 1.68 mg l(-1) nitrite than at
      lower concentrations. Prawns exposed to different concentrations of nitrite-N
      were examined for THC (total hemocyte count), phenoloxidase activity, respiratory
      burst, phagocytic activity and bacterial clearance efficiency. No significant
      differences in THC and phenoloxidase activity were observed among treatments.
      With prawns exposed to nitrite-N for 168 h (7 d) at 1.59 mg l(-1), phagocytic
      activity and clearance efficiency decreased, while at 1.15 mg l(-1) or more,
      respiratory burst increased, generating the superoxide anion at levels considered
      cytoxic to the host. We conclude that nitrite-N at 1.68 mg l(-1) causes
      depression in the immune response and increased mortality in M. rosenbergii
      infected with L. garvieae.

PMID- 12219976
TI  - Model of white spot syndrome virus (WSSV) epidemics in Litopenaeus vannamei.
AB  - White spot syndrome virus (WSSV) is devastating shrimp aquaculture throughout the
      world, but despite its economic importance no work has been done on modeling
      epidemics of this pathogen. Therefore we developed a Reed-Frost epidemic model
      for WSSV in Litopenaeus vannamei. The model includes uninfected susceptible,
      latently infected, acutely infected, and dead infected shrimp. The source of new
      infections during an outbreak is considered to be dead infected shrimp. The
      transmission coefficient, patency coefficient, virulence coefficient, and removal
      coefficient (disappearance of dead infected shrimp) control the dynamics of the
      model. In addition, an explicit area parameter is included to help to clarify the
      distinction between density and absolute shrimp population size. An analysis of
      the model finds that as number of shrimp, initial dose, transmission coefficient,
      patency coefficient, virulence coefficient, or removal coefficient changes, the
      speed of the epidemic changes. The model predicts that a threshold density of
      susceptible shrimp exists below which an outbreak of WSSV will not occur. Only
      initial dose, transmission coefficient, removal coefficient, and area coefficient
      affect the predicted threshold density. Increases in the transmission coefficient
      reduce the threshold value, whereas increases in the other factors cause the
      threshold value to increase. Epidemic models may prove useful to the shrimp
      aquaculture industry by suggesting testable hypotheses, some of which may
      contribute to the eventual control of WSSV outbreaks.

PMID- 12219977
TI  - Detection of marine birnavirus in the Japanese pearl oyster Pinctada fucata and
      seawater from different depths.
AB  - This study examines the seasonal changes of marine birnavirus (MABV) in seawater
      and the Japanese pearl oyster Pinctada fucata reared at different depths (2 and
      15 m). Oysters and seawater were collected in 1998, and a 2-step PCR was carried
      out to detect MABV. Virus isolation was performed on the PCR-positive samples in
      the oyster. The detection rate of the MABV genome in the oyster was low during
      June, but increased after July at both 2 and 15 m depths. MABV was not isolated
      until after September, when isolation rates of 10 to 28.6% were recorded. The
      results suggest that growth of MABV in the oyster is similar at 2 and 15 m depth.
      In contrast, the MABV genome in seawater was present through the year at 15 m
      depth, but was not detected in summer at 2 m. This suggests that the virus is
      destroyed by UV and/or other factors at 2 m in summer, but is stable in deeper
      waters.

PMID- 12219978
TI  - Pathology of cultured paua Haliotis iris infected with a novel haplosporidian
      parasite, with some observations on the course of disease.
AB  - Mortalities among juvenile paua Haliotis iris Martyn 1784 in a commercial culture
      facility were reported in April 2000. Histology of moribund paua showed heavy
      systemic infections of a uni- to multi-nucleate stage of a novel organism later
      confirmed by transmission electron microscopy (TEM) and molecular studies to be a
      haplosporidian. Multinucleate plasmodia up to 25 microm diameter with up to 17
      nuclei were detectable in wet preparations of hemolymph from heavily infected
      paua. The presence of the haplosporidian in the affected facility was associated
      with mortalities of slow growing 'runt' paua during the summer months. Total
      mortalities in affected raceways 6 mo after mortalities began were between 82.5
      and 90%. Heavily infected paua exhibited behavioural abnormalities including
      lethargy, loss of righting reflex, and were easily detached from surfaces. Some
      heavily infected paua exhibited oedema and pale lesions in the foot and mantle,
      but no reliable gross signs of disease were noted. Light infections of the
      haplosporidian were also found in apparently healthy paua from the facility.
      Histology indicated that the early stages of infection were characterised by
      small numbers of plasmodia in the connective tissue surrounding the gut, amongst
      glial cells adjacent to nerves in the mantle and foot and within gill lamellae.
      In heavy infections, large numbers of small plasmodia (mean size 5.5 x 7 microm
      in histological sections) were present in the hemolymph, gills, heart, kidneys,
      mantle, foot, epipodium and connective tissue of the digestive gland. Infections
      were not transferred horizontally at 14 and 19 degrees C after cohabiting heavily
      infected paua with uninfected paua for 3 mo in aquaria, or 3 mo after injecting
      healthy paua with hemolymph containing haplosporidian plasmodia. This may
      indicate that the prepatent period for disease is longer than 3 mo, that disease
      is not expressed below 20 degrees C, or that an intermediate host is required for
      transmission. Spore formation was not observed in juvenile paua but sporocyst
      like bodies containing putative spores were observed amongst haplosporidian
      plasmodia in the right kidney of poorly performing adult paua collected from the
      wild.

PMID- 12219979
TI  - First isolation of largemouth bass virus.
AB  - The first reported fish kill caused by largemouth bass virus (LMBV) occurred in
      1995 in Santee-Cooper Reservoir, South Carolina, USA. Subsequently, this
      iridovirus has been implicated in additional fish kills and has also been found
      in clinically healthy fish in numerous locations in the southeastern USA. We
      compared the virus from Santee-Cooper Reservoir with a virus isolated in 1991
      from large-mouth bass, Micropterus salmoides, from Lake Weir, Florida.
      Restriction fragment length polymorphisms and the DNA sequence of a portion of
      the major capsid protein gene were identical for the South Carolina and Florida
      isolates. These results establish that LMBV was first found in Florida, rather
      than South Carolina. We propose that the name largemouth bass virus continue to
      be used for this virus, rather than alternative names based on geographical
      origin.

PMID- 12219980
TI  - Evaluation of the sulfate dynamics in groundwater by means of environmental
      isotopes.
AB  - Elevated sulfate concentrations and their heterogeneous distribution in the
      drinking water catchment area Torgau-Mockritz (Germany) were investigated by
      means of multiple isotope signatures such as 834S, delta18O-H2O, deltaD, tritium,
      and 85K5r. delta34S values of the groundwater sulfate vary between -19...+ 37 per
      thousand CDT. No simple correlation exists between sulfate concentrations and
      delta34S. Superimposition of different sulfur sources and mobilization processes
      combined with a complicated groundwater movement create a complex distribution
      pattern. The oxidation of reduced sedimentary sulfur has to be regarded as a main
      source of dissolved sulfate at least regionally. Tritium and 14C data revealed
      that old groundwater can be excluded as source for high sulfate contents.
      Correlated temporal variations in the concentrations of tritium and sulfate are
      observed in deeper sampling positions. Highly variable delta18O and 8D, as
      detected in parts of the catchment area, indicate local influences of surface
      water infiltration into the aquifer. The spatial distribution of isotope
      signatures enables the identification of zones with descending younger water or
      hindered groundwater movement and hence provides useful hints for flow modeling.

PMID- 12219981
TI  - Sulfur and oxygen isotope geochemistry of acid mine drainage--the polymetallic
      sulfide deposit "himmelfahrt fundgrube" in Freiberg (Germany).
AB  - We investigated physical, chemical and isotope (S, O) parameters of sulfate from
      acid mine drainage from the polymetallic sulfide ore deposit Freiberg (Gennany),
      which was mined for more than eight hundred years. Two main groups of water were
      distinguished: 1. Flowing mine water with sulfate concentrations of less than
      9,000 mg/l and pH values higher than 3.2, 2. Pore water in weathered low grade
      ores and pools with sulfate concentrations higher than 9000mg/l and pH values
      below 3.2. The sulfur and oxygen isotope composition of sulfate from flowing mine
      waters reflects mixing of sulfate from two sulfur sources: a) atmospheric sulfur
      from precipitation and b) sulfate formed as a result of sulfide oxidation
      processes. Sulfur isotope values of mine water sulfate were used to estimate the
      contribution of sulfate derived through oxidation of sulfides. The sulfur isotope
      composition of pore water sulfate and precipitated sulfate (jarosite) from
      weathered low grade ore samples is identical to the sulfur isotope composition of
      primary sulfides. The oxygen isotope composition of pore water sulfate from low
      grade ore samples indicates that the oxidation process proceeds relatively slowly
      in 02-depleted waters, probably without significant microbial catalysis.

PMID- 12219982
TI  - Towards an inhalative 13C breath test method.
AB  - Customary 13CO2 breath tests--and also 15N urine tests--always start with an oral
      administration of a test substrate. The test person swallows a stable isotope
      labelled diagnostic agent. This technique has been used to study several
      pathophysiological changes in gastrointestinal organs. However, to study
      pathophysiological changes of the bronchial and lung epithelium, the inhalative
      administration of a stable isotope labelled agent appeared more suitable to us.
      [1-13C]Hexadecanol and [1-13C]glucose were chosen. Inhaled [1-13C]hexadecanol did
      not yield 13CO2 in the exhaled air, but [1-13C]glucose did. To study the
      practicability of the [1-13C]glucose method and the reproducibility of the
      results, 18 inhalation tests were performed with healthy subjects. In 6 self
      tests, the optimum inhalative dose of [13C]glucose was determined to be 205 mg.
      Using the APS aerosol provocation system with the nebulizer 'Medic Aid' (Erich
      Jaeger Wurzburg), a 25% aqueous solution was inhaled. Then, breath samples were
      collected at 15 min. intervals and analysed for 13CO2. 75-120 min after the end
      of inhalation a well-reproducible maximum delta13C value of 6%o over baseline
      (DOB) was detected for 12 healthy probands. Speculating that the pulmonary
      resorption of the [13C]glucose is the rate-limiting step of elimination,
      decompensations in the epithelium ought to be reflected in changed [1-13C]glucose
      resorption rates and changed 13CO2 output. Therefore, we speculate that the
      inhalation of suitable 13C-labelled substrates will pave the way for a new group
      of 13CO2 breath tests aiding investigations of specific pathophysiological
      changes in the pulmonary tract, such as inflammations of certain sections and
      decompensations of cell functions.

PMID- 12219983
TI  - [13C]aminopyrine and [13C]caffeine breath test: influence of gender, cigarette
      smoking and oral contraceptives intake.
AB  - The [13C]aminopyrine breath test ([13C]ABT) measures the global activity of
      cytochrome P450 in vivo and is a sensitive indicator of liver metabolic
      dysfunction. The present study aims to determine whether gender and cigarette
      smoking influence the results of [13C]ABT as well as to confirm the effect of
      oral contraceptive steroids (OCS) intake on this metabolic test. Hundred and ten
      healthy subjects, including men and women, smoker and non-smoker, women taking
      OCS or not, were phenotyped for CYP1A2 using the [13C]caffeine breath test and
      underwent a [13C]ABT. Both tests showed large inter-individual variations in
      accordance with that of CYP450 liver content. [13C]ABT was sensitive enough to
      point out a significant induction or inhibition related to cigarette smoking
      habits or OCS. The combined effect of smoking and OCS resulted in an overall
      unchanged metabolic activity. Consequently, the impact of the studied conditions
      on the [13C]ABT parameters must be considered by clinicians or clinical
      investigators.

PMID- 12219984
TI  - Analysis of 13C-mixed triacylglycerol in stool by bulk (EA-IRMS) and compound
      specific (GC/MS) methods.
AB  - This paper was presented in poster form at the 17th International Congress of
      Nutrition, August 27-31, Vienna, Austria (Annals of Nutrition & Metabolism 2001;
      45(Suppl.1):349). Some of the data were also presented in poster form at the
      British Society of Gastroenterology Meeting, March 18-21, Glasgow, UK (Gut 2001;
      48(Suppl.1):A91). The 13C-mixed triacylglycerol (MTG) breath test is used to
      measure intraluminal fat digestion. In normal digestion, 20-40% of the ingested
      13C label is recovered in breath CO2. We aimed to identify the proportions of
      ingested label excreted in stool, as well as breath following ingestion of 13C
      MTG by children with impaired exocrine pancreatic function and healthy controls.
      13C enrichment of breath samples was measured by continuous flow isotope ratio
      mass spectrometry (IRMS) and cumulative percent dose recovered (cPDR) in 10 h was
      calculated. Total 13C of a faecal fat extract from each stool was measured by
      elemental analyser-IRMS, and 13C enrichment and concentration of the TBDMS
      derivative of octanoic acid was measured by GC/MS after hydrolysis of the fat
      extract. Stool 5-day cPDR was calculated. Mean breath cPDR was 35%. Mean cPDR in
      stool by combustion-IRMS and GC/ MS, respectively, was 0.8% and 1.0%. Therefore,
      the remaining 64% of the 13C label must remain in the body and variability in
      breath cPDR is due to postabsorptive rather than predigestive factors.

PMID- 12219985
TI  - Stability of iodine content in iodized salt.
AB  - lodization of consumed salts is mandatory in many countries fighting against to
      iodine deficiency. In salts iodine stability is affected by storage conditions.
      In this study, stabilization of iodine in salt has been determined by using
      Isotope Dilution Analysis. Heating, heating with oxidizing agent, incubation by
      time were the parameters which have been determined. Iodine loss was 41.16% by
      heating at 200 degrees C up to 24 hours. When the iodized salt heated with
      oxidized agent iodine loss rose up to 58.46% in 24 hours. Iodine loss mechanism
      seems similar in both cases. However iodine loss is greater in the presence of
      H202. After the salt was stored at room temperature with a relative humidity of
      30%-45% and in sealed paper bags for three years, 58.5% of iodine content lost in
      approximately 3.5 years.

PMID- 12219986
TI  - Airborne nitrogen input at four locations in the German State of Saxony-Anhalt-
      measurements using the 15N-based ITNI-system.
AB  - The amount of atmospheric N deposition in Germany is actual rather uncertain.
      Estimates using standard methods indicate an N deposition of 30-35 kg N/ha x
      year. However, the results of long-term field experiments and newly by the ITNI
      (Integrated Total Nitrogen Input) system could prove a much higher N input of
      about 50-60 kg N/ha x year. The reason for this difference is that standard
      methods use wet-only or bulk collectors, which neglect gaseous and organic N
      deposition as well as direct N uptake by aerial plant parts. By contrast, the
      ITNI-system is able to measure the total atmospheric N input using the 15N
      isotope dilution method. The input of airborne N into a soil/ plant system leads
      to a dilution of the abundance of a previously applied 15N tracer over a defined
      time period. The atmospheric N deposition can be calculated from this dilution.
      To estimate the actual N input in Central Germany, ITNI measurements were carried
      out from autumn 1998 to autumn 2000 at four locations in the German state of
      Saxony-Anhalt. Atmospheric N depositions between 45 and 75 kg N/ha x year were
      determined depending on the location. These results closely match to N balances
      of long-term field experiments. Furthermore, a relationship was found between N
      deposition and the plant species used as well as plant development.

PMID- 12219987
TI  - Using environmental isotopes 2H and 18O for identification of infiltration
      processes in floodplain ecosystems of the River Elbe.
AB  - We examined a floodplain area in the middle section of the river Elbe Valley with
      regard to hydrogeological and hydrological processes using isotopic methods. Over
      two years, river water and groundwater have been analysed for temporal and
      spatial chemical and isotopic (delta2H and delta18O) changes. By these methods we
      assessed the flow dynamics of the river-groundwater infiltration system. At low
      and mean river stages there is a general hydraulic gradient from the higher areas
      at the margin of the valley towards the floodplain. During floods river water
      infiltrates into the adjacent aquifer not primarily through the river banks but
      first through surface water inflow from north to south, via depressions and
      gullies from the back of the floodplain. The early stage of river water
      infiltration is characterized by a sharp decrease in conductivity and in
      concentrations of SO4(2-) and Cl- in the hydraulically connected shallow aquifer.
      delta2H and delta18O values show a similar tendency. We observed a significant
      minimum in stable isotope ratios during the flood in March 1999. Using a simple
      mixing equation it was calculated that the groundwater in the upper, shallow
      aquifer consists of around 70% river water in the transition zone (well 13)
      during flooding.

PMID- 12219988
TI  - Variations of lead isotopes and airborne particulate concentrations from the
      Kozani basin, West Macedonia, Greece.
AB  - The spread and variation in 206Pb/207Pb ratios make Pb isotopes a powerful tool
      when it comes to detecting trends in airborne particulates originating mainly
      from power plants. This study was conducted to determine the source of pollution
      in Kozani area, an affected industrial area. Lead isotopic ratios of air filters
      under certain meteorological conditions were compared to Pb isotope analyses
      sampled from lignite mines, but also to Pb isotope analyses of cultivations in
      soil originating from the reclamation of old abandoned lignite-mines. The
      particles taken into consideration have an aerodynamic diameter less than 10
      microm (PM10). The measurements were carried out in a central part of the town of
      Kozani, West Macedonia, for one year observation period. The lead isotope values
      of air filters and of wheat in the Kozani area are between the values of lignite
      Pb and of Greek gasoline.

PMID- 12219990
TI  - Bioaccumulation of 65Zn2+ ions by some hydrophytic plants.
AB  - This paper deals with a study on the retention of radioactive ions 65Zn2+ from
      diluted waste solutions by the hydrophytic plants Lemna minor, Elodea canadensis,
      Pistia stratiotes and Riccia fluitans. The bioaccumulation degree decreases in
      the following order: Riccia fluitans approximately Pistia stratiotes > or = Lemna
      minor > Elodea canadensis The possibility to improve the bioaccumulation degree
      varying the temperature and the solution pH, in the absence of other cations, has
      been studied. The thin layer radiochromatography method has been used and it
      proved that the saccharides and lipids are the biochemical fractions responsible
      for the 65Zn2+ retention.

PMID- 12219989
TI  - Assessment of intestinal absorption of trace metals in humans by means of stable
      isotopes.
AB  - This study is aimed to demonstrate the feasibility of stable isotopes for the
      assessment of reliable data on fractional intestinal absorption of trace metals
      in healthy humans. Among the various methods available, the double isotope
      technique, i.e. one isotope given orally together with the test substance to be
      investigated and another isotope injected intravenously to correct for retention
      and endogenous excretion of the particular trace metal, provides quantitative
      figures of intestinal absorption at reasonable expenses with regard to costs for
      materials and number of samples to be evaluated. The trace metals exemplarily
      included in this study, i.e. iron, cobalt and molybdenum show diverging relations
      between absorbed fractions and amounts administered which are indicative for
      different regulatory mechanisms of their body content. Food ligands influence the
      fractional absorption significantly so that the uptake from a composite meal
      cannot be derived from results on uptake from particular foodstuffs. Therefore,
      validated data on the behaviour of intestinal absorption will significantly
      contribute to a better understanding of human trace metal metabolism.

PMID- 12219991
TI  - Correlation between short-term and long-term radon measurements.
AB  - In selected kindergartens and schools, long-term average indoor air radon
      concentrations were measured by two-month exposure of etched track detectors.
      Short-term average concentrations were obtained from 7-10 day continuous radon
      recordings during the exposure of etched track detectors. Only in about 1/3 of
      cases both averages did agree within +/- 20%; otherwise they differ considerably.
      The assumption that short-term results can substitute for long-term data, which
      is sometimes made to correct radon exposure estimated on the basis of
      concentrations obtained by etched track detectors, should therefore be treated
      with caution.

PMID- 12219992
TI  - Thermal-field propagation in an exocontact zone of a magmatic body and its impact
      on radiogenic isotope concentrations in minerals.
AB  - In application of radioactive isotope systems (K-Ar, Rb-Sr etc.) during the last
      decades, experience was gained not only on their geochronometrical uses, but also
      on estimations of some important parameters of geological processes, especially
      temperatures and durations of superimposed thermal events. In this paper, the
      formation of an exocontact thermal field of a magmatic intrusion is considered as
      a spreading of a thermal source delta-function. Appropriate solutions of the heat
      transfer equation are deduced and correlated with diffusion parameters of the
      radiogenic argon, coupling radioactive, thermal and kinetic parameters in an
      exocontant zone of a magmatic body. These solutions were used for quantitative
      reinterpretations of data taken from Hart's classical paper [The petrology and
      isotopic mineral age relations of a contact zone in the Front Range, Colorado. J.
      Geol., 1964, v. 72, pp. 493-525]. Theoretic and measured radiogenic argon and
      strontium concentrations within exocontact aureoles are found to be in good
      concordance.

PMID- 12219993
TI  - Clinical, genetic and histopathologic findings in two siblings with muscle-eye
      brain disease.
AB  - PURPOSE: We present the clinical, genetic and histopathologic findings in two
      siblings with Muscle-Eye-Brain Disease (MEB-D), an autosomal recessive disease
      characterized by mental retardation, muscular dystrophy, retinal hypoplasia and
      brain abnormalities. METHODS: Clinical, histopathologic and gene mapping studies
      of a family with two normal and two children with MEB-D. RESULTS: Two siblings
      presented in the first few months of life with developmental delay, hypotonia,
      and strabismus. MRI of the brain showed colpocephaly, pontine and cerebellar
      atrophy, and diffuse white matter disease. Both patients were blind and had high
      myopia, strabismus, and retinal and optic nerve abnormalities. The older boy had
      glaucoma. Both children died from uncontrolled seizures. There was retinal,
      choroidal and RPE atrophy and optic nerve hypoplasia on ocular histopathology.
      Both patients shared the same parental haplotypes at the MEB locus on chromosome
      1p, while an unaffected sibling did not, indicating possible linkage to the MEB
      locus. CONCLUSIONS: Patients with MEB-D have severe visual impairment from
      retinal and optic nerve hypoplasia. High myopia appears to be a consistent
      finding. The ocular manifestations of MEB-D appear to be distinct from those of
      patients with Walker-Warburg syndrome.

PMID- 12219994
TI  - Comparison of emedastine 0.05% or nedocromil sodium 2% eye drops and placebo in
      controlling local reactions in subjects with allergic conjunctivitis.
AB  - PURPOSE: To assess the efficacy of nedocromil sodium 2% eye drops and emedastine
      difumarate 0.05% eye drops in controlling the ocular allergic reaction induced by
      conjunctival allergen challenge (CAC). METHODS: Thirty subjects with a personal
      history of allergic conjunctivitis were enrolled (first visit). At the second
      visit each subject randomly received emedastine 0.05% or nedocromil 2% in one eye
      and placebo in the other eye. Five minutes after the medication the offending
      allergen was instilled in both eyes. Ocular redness and itching were evaluated
      according to a standardized scoring system at 3, 10 and 20-minute intervals after
      instillation of the allergen. After one week (third visit) the whole procedure
      was repeated using the placebo in the eye used as control during second visit and
      one of the trial drug that was not used at second visit in the other eye (either
      emedastine or nedocromil). RESULTS: Emedastine 0.05% and nedocromil 2% eye drops
      were more effective than placebo in controlling ocular redness and itching
      (p<0.01). Emedastine was more effective (p<0.01) than nedocromil in alleviating
      redness and itching 3 and 10 minutes after application of the allergen.
      CONCLUSIONS: Emedastine 0.05% appeared superior to nedocromil 2% in producing
      immediate relief when subjects with allergic conjunctivitis were exposed to the
      offending allergen.

PMID- 12219995
TI  - Corneal epithelial keratitis in herpes zoster ophthalmicus: "delayed" and "sine
      herpete". A non-contact photomicrographic in vivo study in the human cornea.
AB  - PURPOSE: To investigate the origin of corneal epithelial keratitis occurring
      without accompanying herpes zoster ophthalmicus (HZO) cutaneous rash. METHODS:
      Corneal epithelial lesions in seven patients (four with a history of classical
      HZO with cutaneous rash, one of herpes zoster oticus, and two with no history of
      herpes zoster, were examined with the slit lamp and photographed by non-contact
      in vivo photomicrography. The findings were compared with lesions in classical
      acute HZO. Polymerase chain reaction (PCR) was done in three patients. RESULTS:
      Slit lamp appearance, morphology at higher magnification, and kinetics of the
      lesions were indistinguishable from classical acute HZO. PCR was positive for
      varicella-zoster virus DNA in all three samples. CONCLUSIONS: The findings
      strongly suggest that HZO typical corneal epithelial lesions occurring in the
      absence of cutaneous rash are in fact recurrent episodes of virus shedding.

PMID- 12219996
TI  - Pulsatile ocular blood flow during pregnancy.
AB  - PURPOSE: To study pulsatile ocular blood flow (POBF) throughout pregnancy.
      METHODS: We enrolled twenty-seven healthy women in the first trimester of
      gestation, only ten of which were followed through the second trimester, and
      fourteen non pregnant healthy women. In each subject we measured POBF with the
      POBF pneumotonometer (OBF Ltd. UK), IOP, blood pressure (BP) and heart rate (HR).
      An unpaired Student t-test was used to compare pregnant women with non-pregnant
      women, and a two-tailed paired Student t-test was used to compare the same women
      in the first and second trimester of pregnancy. p <0.05 is considered
      statistically significant. RESULTS: Results are presented as means +/- SD. In the
      first trimester of pregnancy the age was 32 +/- 6, POBF 1516.4 +/- 382 ml/min,
      IOP 13 +/- 3 mmHg, BP 92 +/- 6 mmHg, and HR 86 +/- 14 beats/min. In the second
      trimester POBF was 1629.11 +/- 352.4 ml/min, intraocular pressure (IOP) 12 +/- 3
      mmHg, BP 96 +/- 3 mmHg, and HR 93 +/- 10 beats/min. In the control group the age
      was 27 +/- 9, POBF 972.23 +/- 329.3 ml/min, BP 88 +/- 4.3 mmHg, and HR 80 +/- 14
      beats/min. POBF increases during the first trimester (p = 0.00008). In the second
      trimester POBF was higher compared to the first trimester (p = 0.0008). Non
      significant differences were observed for the other parameters. CONCLUSIONS: The
      POBF increases throughout gestation. During pregnancy there is an increase in
      estrogen which induces endothelial-dependent vasodilatation in several tissues.
      The estrogen changes may influence POBF.

PMID- 12219998
TI  - Intraocular pressure response of capsular glaucoma and primary open-angle
      glaucoma to selective Nd:YAG laser trabeculoplasty: a prospective, comparative
      clinical trial.
AB  - PURPOSE: To compare the intraocular pressure (IOP) response of uncontrolled
      capsular glaucoma (CG) and primary open-angle glaucoma (POAG) to selective laser
      trabeculoplasty (SLT) in a prospective clinical trial. METHODS: Ten eyes often
      patients suffering from uncontrolled CG (CG Group) and ten eyes of ten patients
      with uncontrolled POAG (POAG Group) were treated with a frequency-doubled, Q
      switched Nd:YAG laser (532 nm). The baseline characteristics were similar in both
      groups. IOP was measured before and 1 day, 1 week, 1 month and 3, 6, 9, 12, 15
      and 18 months after treatment. Success was defined as IOP more than 20% lower
      than before treatment. Any change of hypotensive medication led to the subjects'
      exclusion from the study. The two groups were compared using the independent
      sample t test for continuous variables and the log-rank test for survival
      analysis. A value of p<0.05 was considered significant. RESULTS: The mean follow
      up was 12.0 months (SD 5.5) for the CG group and 13.5 months (SD 4.3) for POAG
      (n.s.). No significant difference was found between the two groups for mean
      pretreatment IOP (23.6 mmHg +/- 5.70 in the CG group and 22.8 mmHg +/- 2.44 in
      the POAG group) or for mean IOP and mean IOP reductions during the follow-up. At
      all follow-up visits, IOP was reduced less in the CG group than in the POAG group
      (24.8% +/- 11.15 vs. 27.7% +/- 9.91 at 6 months, 22.0% +/- 6.66 vs. 30.6% +/-
      6.35 at 12 months, and 31.4% +/- 5.55 vs. 35.1% +/- 1.75 at 18 months), but the
      difference was significant only at 12 months. Kaplan-Meier survival analysis gave
      an 18-month success rate of 64% in the CG group and 78% in the POAG group, with
      no significant differences between the groups. CONCLUSIONS: SLTis an effective
      procedure forlowering IOP in CG and POAG eyes, although the effect seems to last
      less in CG eyes.

PMID- 12219997
TI  - Effects of L-NAME and timolol on aqueous IL-1beta, IL-6, IL-8, TNF-alpha and NO
      levels after Nd:YAG laser iridotomy in rabbits.
AB  - PURPOSE: Pro-inflammatory cytokines are produced by tissues and play a vital role
      in the host inflammatory response and uveitis. Nitric oxide (NO) can be produced
      in large amounts as a response to experimentally-induced uveitis or cytokines. In
      this study, we measured the levels of pro-inflammatory cytokines such as
      interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha and free
      radical in aqueous humor after Nd:YAG laser iridotomy in rabbits, and
      investigated whether timolol maleate an anti-glaucoma drug, or a NO synthase
      inhibitor, NG-nitro-L-arginine methyl esther (L-NAME) had an inhibitory effect on
      these molecules, since L-NAME is a known anti-inflammatory agent in rabbits.
      METHODS: Bilateral experimental Nd:YAG laser iridotomy (power 7.5 mJ, mode single
      burst, aiming beam 4) was performed on 18 rabbits under general plus topical
      anesthesia. Aqueous humor samples were taken by clear corneal paracentesis
      preoperatively, and 1 and 24 h postoperatively. Six rabbits (12 eyes) were given
      bilateral topical timolol maleate 0.5% (Timoptic) drop b.i.d. (group 1), six
      rabbits (12 eyes) received bilateral 0.1 ml subconjuntival injections of L-NAME
      (150 mg/kg) (group 2), and six rabbits (12 eyes) were treated with topical
      balanced salt solution (BSS) b.i.d. (control). RESULTS. Preoperative cytokine and
      NO levels were comparable in the three groups, with no significant differences.
      In addition, there was no significant difference in baseline cytokine levels
      between the right and left eyes. In all groups, pre- and postoperative mean IL
      1beta levels were below the detection limit of the assay (<5.0 pg/ml). In the
      control group, postoperative mean IL-6, IL-8 and NO levels were significantly
      higher after Nd:YAG laser iridotomy than before (for each, p < 0.01). Timolol and
      L-NAME both inhibited the rise in IL-8 and TNF-alpha levels. Timolol also
      inhibited the rise in IL-6 but not NO. L-NAME had an inhibitory effect against
      NO, but not IL-6. CONCLUSIONS: L-NAME has an inhibitory effect on IL-8, TNF-alpha
      and NO, but not on IL-6. Timolol had inhibitory effects on IL-6, IL-8 and TNF
      alpha, but not on NO. These preliminary experimental results might help in
      assssing the effect of Nd:YAG laser iridotomy in aqueous humor, and to understand
      the inhibitory effects of timolol and L-NAME against these molecules.

PMID- 12219999
TI  - Risk factors for anatomical success and visual outcome in patients undergoing
      silicone oil removal.
AB  - PURPOSE: To define risk factors for anatomical success and visual outcome in
      patients undergoing removal of silicone oil. METHODS: This retrospective study
      included patients who had silicone oil removed at this hospital between 1996 and
      2000. All were followed for at least six months. Patients with recurrent retinal
      detachment after silicone oil removal were compared with patients without this
      complication. We also compared patients whose vision improved or stabilized with
      patients whose vision deteriorated. Risk factors for anatomical success and
      visual outcome were identified. RESULTS: We analysed 94 eyes of 92 patients with
      silicone oil removal. Nineteen eyes (20%) had recurrent retinal detachment, and
      in 30 eyes (32%), the vision deteriorated after removal of the oil. Initial
      vision less than ambulatory vision, initial pathology of giant retinal tears and
      recurrent retinal detachment, postoperative hypotony and postoperative epiretinal
      membrane occurred more frequently in eyes with than without recurrent retinal
      detachment. Pre- and postoperative hypotony, postoperative epiretinal membranes
      and postoperative recurrent retinal detachment were also more frequent in eyes
      with deteriorated vision. CONCLUSIONS: When treating giant retinal tears or
      recurrent retinal detachments with silicone oil tamponade, surgeons and their
      patients need to be aware of the higher possibility of unfavorable results,
      particularly when the initial vision is less than ambulatory vision. The presence
      of risk factors before and after silicone oil removal should remind surgeons of
      the higher risk profile of this particular surgery.

PMID- 12220000
TI  - Surgical management of retinal detachment with choroidal coloboma.
AB  - PURPOSE: To verify the functional and anatomical results of retinal detachments
      related to choroidal coloboma. METHODS: Seven eyes with retinal detachment
      secondary to retinal breaks at the margin of or within a choroidal coloboma were
      analysed retrospectively. RESULTS: Scleral buckling was performed in five of the
      seven eyes; two needed additional pars plana vitrectomy (PPV) with internal
      tamponade using silicone oil to reattach the retina. In two eyes PPV with
      internal tamponade using silicone oil or gas was used as a primary procedure. All
      seven eyes were reattached. Five eyes (71.4%) showed improvement or had visual
      acuity of 20/400 or better after surgery, but two remained unchanged.
      CONCLUSIONS: Retinal detachment secondary to choroidal coloboma can be treated
      successfully by scleral buckling or PPV with internal tamponade.

PMID- 12220001
TI  - Traumatic rupture of the globe caused by cow horns.
AB  - PURPOSE: We investigated the epidemiology, clinical findings and functional
      outcome of open-globe injuries caused by cow horns over a 50-year period in
      eastern Switzerland. METHODS: We retrospectively evaluated the files of cases
      with ruptures of the globe caused by cow horns between 1950 and 1999. RESULTS: We
      found 59 cases with ruptures of the globe by cow horns, accounting for 5% of all
      open-globe injuries. The incidence of these accidents did not change during the
      observation period. Twenty-two eyes (37%) were enucleated. Only 7 eyes (12%)
      retained a vision of > or = 0.1. Between 1950 and 1989 only 2/43 eyes (5%)
      reached a vision of > or = 0.1. In the 1990's, with the introduction of vitreous
      surgery 5/16 eyes (31%) had a vision of > or = 0.1. Four patients (7%) had
      blinding eye disease in the partner eye, and three (5%) had a second open-globe
      trauma. CONCLUSIONS: In rural regions, with cattle breeding, open-globe injuries
      by cow horns are relatively common and the frequency is still the same as 50
      years ago. The visual prognosis of these eyes is still guarded, but functional
      results have improved with the introduction of vitreous surgery. Patients who
      have had a rupture of the globe appear to have an increased risk for partner eye
      trauma. Therefore, all efforts are justified to preserve even limited vision in
      severely injured eyes.

PMID- 12220002
TI  - Low-dose intravenous methylprednisolone or conservative treatment in the
      management of traumatic optic neuropathy.
AB  - PURPOSE: To compare the efficacy of low-dose intravenous methylprednisolone or
      conservative treatment in the management of traumatic optic neuropathy. METHODS:
      A non-randomized retrospective study of 21 patients (21 eyes) with traumatic
      optic neuropathy treated between October 95 and November 97 in a tertiary
      ophthalmology unit. Traumatic optic neuropathy was defined as traumatic visual
      loss with afferent pupillary defect in the absence of direct injury to the globe
      or optic nerve. The median follow-up period was one year. Nine patients were
      treated with 125-250 mg methylprednisolone 6-hourly intravenously for a mean of
      3.3 days (range 2-5 days) and 12 patients were treated conservatively. Visual
      acuity (VA) was measured with a Snellen chart before and after treatment at each
      follow-up visit. Visual recovery was defined as an improvement of 2 or more
      Snellen lines one week post-injury or later. RESULTS: The patients' mean age was
      37.1 years (range 12-65 years). There were more males (90.5%) than females
      (9.5%). Traumatic optic neuropathy was in 12 right eyes and 9 left eyes. The
      cause of injury included traffic accidents (52.4%), falls (28.6%), assault
      (14.2%) and others (4.8%). The mean interval between the injury and steroid
      therapy was 3.6 days (range 1-11 days). Visual recovery was observed in 44.4% of
      eyes treated with methylprednisolone and in 33.3% treated conservatively (p =
      0.673, Fisher's exact test). CONCLUSIONS: Intravenous methylprednisolone at the
      dosage and duration used in this retrospective study did not significantly
      improve the visual recovery of eyes with traumatic optic neuropathy compared to
      conservative treatment. However, this small sample may not be sensitive enough to
      detect a small difference in visual recovery rates, and further studies with
      larger samples may be warranted.

PMID- 12220003
TI  - Progressive external ophthalmoplegia: a paraneoplastic manifestation of lymphoma.
AB  - PURPOSE: Paraneoplastic neurological syndromes are well-known sequelae of some
      malignancies. To our knowledge, a syndrome mimicking progressive external
      ophthalmoplegia had never been reported preceding the diagnosis of a lymphoma.
      CASE REPORT: A 63-year-old man developed progressive external ophthalmoplegia,
      without any other neurological symptoms, as the initial manifestation of a
      follicular lymphoma grade III. The ophthalmoplegia resolved after two cycles of
      combination chemotherapy. CONCLUSIONS: The ophthalmologist, when confronted with
      a progressive external ophthalmoplegia, should consider a neurological
      paraneoplastic syndrome associated with a tumor as a possible diagnosis.

PMID- 12220004
TI  - Pleomorphic adenocarcinoma of the ciliary epithelium: a clinicopathological,
      immunohistochemical, ultrastructural, DNA-ploidy and comparative genomic
      hybridization analysis of an unusual case.
AB  - PURPOSE: To describe detailed phenotypic and genotypic analysis of a pleomorphic
      adenocarcinoma of the ciliary epithelium (CE). CASE REPORT: An 86-year-old white
      woman developed an enlarging mass protruding from her previously eviscerated left
      eye 2 months postoperatively. Based on light and ultrastructural microscopy, the
      final diagnosis was a pleomorphic adenocarcinoma of the ciliary epithelium (CE).
      DISCUSSION: Cell proliferation indices confirmed the unusually rapid growth rate
      of this tumor; the peridiploid DNA content might explain the relatively low
      incidence of distant metastases. An imbalance of the chromosome 6 was also found
      by Comparative Genomic Hybridization (CGH).

PMID- 12220005
TI  - Metastatic cutaneous melanoma to the vitreous cavity masquerading as intermediate
      uveitis.
AB  - PURPOSE: To report a patient with metastatic cutaneous melanoma (MCM) presenting
      as intermediate uveitis. METHODS: We examined a 49-year-old man with malignant
      cutaneous melanoma and central nervous system (CNS) metastasis who was initially
      treated for bilateral intermediate uveitis. Biomicroscopic examination disclosed
      a normal anterior segment and vitreous organization with red blood cells (RBC)
      and some non-pigmented cells in both eyes. Funduscopy disclosed a retinal
      metastasis in the right eye, but vitreous organization precluded visualization of
      the retina in the left eye. RESULTS: The first diagnostic vitrectomy was negative
      for malignant cells in the left eye. However, progressive worsening of the
      condition persuaded us to repeat vitrectomy in the left eye and to do it in the
      right eye too. Vitreous samples were positive for malignant melanoma cells in
      both eyes. CONCLUSIONS: Metastatic cutaneous melanoma to the vitreous cavity is
      exceedingly rare and may masquerade as intermediate uveitis. It should be
      considered in the differential diagnosis of unusual uveitis and masquerade
      syndromes.

PMID- 12220006
TI  - Central retinal artery occlusion associated with ocular Behcet's disease.
AB  - PURPOSE: To report a case of central retinal artery occlusion associated with
      ocular Behcet's disease (BD) and briefly discuss retinal vasculitis due to BD.
      CASE REPORT: A 52-year-old man, diagnosed as BD 22 years ago and followed up with
      ocular involvement for six years presented with sudden loss of vision. The
      clinical diagnosis was central retinal artery occlusion. RESULTS: No other
      associated systemic diseases were found and the case was classified as a
      complication of retinal vasculitis due to BD. CONCLUSIONS: Although the arteries
      are rarely affected in retinal vasculitis due to BD, it has to be considered in
      the differential diagnosis of retinal arterial occlusions especially in countries
      where the disease is prevalent. To our knowledge, this is the first reported case
      of ocular BD complicated with central retinal artery occlusion.

PMID- 12220007
TI  - Exposure keratopathy following phacoemulsification under local anaesthesia.
AB  - PURPOSE: Report a series of patients with exposure keratopathy following
      phacoemulsification under local anaesthesia. METHODS: A case series. RESULTS:
      Four patients were found to have exposure keratopathy within hours after surgery
      resulting in a visit to the casualty on the day of surgery. CONCLUSIONS: One
      should anticipate the possibility of lagophthalmos and assess the blink reflex at
      the end of surgery. If the reflex is poor, patching the eye or taping the lids
      should be undertaken to prevent this complication.

PMID- 12220008
TI  - Intraoperative capsular block syndrome masquerading as expulsive hemorrhage.
AB  - PURPOSE: To describe the clinical features of two cases of intraoperative
      capsular block syndrome (CBS) mimicking expulsive hemorrhage. SETTING: The Eye
      Institute at Tan Tock Seng Hospital, National Healthcare Group, Singapore.
      METHODS: Two case reports. RESULTS: Two patients underwent phacoemulsification
      under retrobulbar anesthesia and developed severe globe hardening, shallow
      anterior chamber (AC) and uveal prolapse intraoperatively after hydrodissection.
      The AC spontaneously deepened in one patient and the operation was converted to
      extracapsular cataract surgery on suspicion of CBS with posterior capsule
      rupture, which was confirmed after nucleus expression; anterior vitrectomy was
      done and an anterior chamber lens implanted. At the eight post-operative month,
      his best-corrected visual acuity was 6/24 secondary to an epiretinal membrane in
      the macula. CBS, however, was not recognized in the other patient and caused
      posterior lens dislocation during attempted phacoemulsification. This patient
      underwent vitrectomy, removal of the lens nucleus and insertion of a posterior
      chamber intraocular lens in the sulcus the next day. His best-corrected visual
      acuity was 6/9 at the tenth postoperative month. CONCLUSIONS: Intraoperative CBS
      may mimic expulsive hemorrhage. Early diagnosis of this condition and proper
      management optimizes the visual outcome.

PMID- 12220009
TI  - Valsalva retinopathy induced by labour.
AB  - PURPOSE: To describe a patient with Valsalva retinopathy induced by labour.
      METHODS: Case report. RESULTS: A 29-year-old woman at her second pregnancy
      complained of a sudden loss of vision in her left eye during spontaneous labour.
      Visual acuity was reduced to counting fingers. Funduscopy revealed a large
      preretinal hemorrhage at the macula in the left eye. Three weeks after delivery,
      the hematoma was treated with Nd:YAG laser. Two weeks after treatment, visual
      acuity was 20/20 and the premacular hemorrhage had resolved. CONCLUSIONS: A rise
      in intra-abdominal pressure during labour may result in Valsalva retinopathy.
      Nd:YAG laser may be useful in treating such hemorrhage.

PMID- 12220010
TI  - Management of incontinentia pigmenti: a case of monolateral preretinal
      fibrovascular proliferations adjacent to snail-track degeneration areas.
AB  - PURPOSE: To report a case of monolateral preretinal fibrovascularproliferations
      in a young adult woman, who had suffered from incontinentia pigmenti (IP) during
      her first month of life. METHODS: Case report. RESULTS: Circumscribed preretinal
      fibrovascular proliferations, adjacent to a mid-peripheral area of snail track
      degeneration, were occasionally diagnosed in the left eye of an asymptomatic 18
      year-old white female. Careful ocular examination did not reveal any cause of the
      monolateral vascular abnormalities observed in the posterior segment. A detailed
      medical history brought to light that the patient has suffered infantile IP, like
      four other females in her family. The patient did not present any evident
      malformation of teeth, nails, skeleton or hair. A cytogenetic linkage study
      documented a chromosomal aberration in the Xq28 band, which confirmed the
      diagnosis of familial IP (type 2). The fluorescein angiography findings clearly
      illustrated the minimal retinal involvement in the course of IP. CONCLUSIONS:
      This case shows that a wide range of etiologies must be considered in patients
      presenting monolateral preretinal fibrovascular proliferations. To correctly
      manage these uncommon, inherited or acquired, retinal diseases it is better to do
      a mid-term follow-up, rather than operate immediately, and this enabled us to
      observe the natural course of the lesion, while awaiting a definitive diagnosis.

PMID- 12220011
TI  - Determination of capsaicin, nonivamide, and dihydrocapsaicin in blood and tissue
      by liquid chromatography-tandem mass spectrometry.
AB  - A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS
      MS) method for the analysis of capsaicin, nonivamide, and dihydrocapsaicin in
      blood and tissue has been developed. The method utilized a one-step liquid-liquid
      extraction that yielded an approximate 90% recovery of capsaicinoids from blood.
      Chomatographic separation of the capsaicinoids was achieved using a reversed
      phase high-performance liquid chromatography column and a stepwise gradient of
      methanol and distilled water containing 0.1% (v/v) formic acid. Identification
      and quantitation of the capsaicinoids was achieved using electrospray ionization
      tandem mass spectrometry monitoring the precursor-to-product-ion transitions for
      the internal standard octanoyl vanillamide (m/z 280 --> 137), capsaicin (m/z 306 
      -> 137), dihydrocapsaicin (m/z 308 -->137), and nonivamide (m/z 294 --> 137).
      Calibration curves, 1.0 to 250 ng/mL, were constructed by plotting concentration
      versus peak-area ratio (analyte/internal standard) and fitting the data with a
      weighted quadratic equation. The accuracy of the assay ranged from 90% to 107%
      for all analytes. The intra-assay precision (%RSD) for capsaicin was 4% at 2.5
      ng/mL, 3% at 10 ng/mL, and 7% at 100 ng/mL. The interassay precision (% RSD) for
      capsaicin was 6% at 2.5 ng/mL, 6% at 10 ng/mL, and 7% at 100 ng/mL. Similar
      values for inter- and intra-assay precision were obtained for nonivamide and
      dihydrocapsaicin. This method was used to assay for capsaicinoids in blood and
      tissue samples collected from rats exposed to capsaicinoids via nose-only
      inhalation. The concentration of capsaicin in these samples ranged from < 1.0 to
      90.4 ng/mL in the blood, < 5.0 to 167 pg/mg in the lung, and < 2.0 to 3.4 pg/mg
      in the liver.

PMID- 12220012
TI  - Simultaneous determination of nitrate and nitrite in human plasma by gas
      chromatography-mass spectrometry.
AB  - We devised a sensitive and simple method for the simultaneous determination of
      nitrate and nitrite in human plasma, using extractive alkylation. These inorganic
      anions were alkylated with pentafluorobenzyl bromide, using
      tetradecyldimethylbenzylammonium chloride as the phase-transfer catalyst, with
      1,3,5-tribromobenzene as an internal standard. The derivatives were analyzed by
      gas chromatography-mass spectrometry, using the negative-ion chemical ionization
      mode with isobutane as the reagent gas. Calibration curves for nitrate and
      nitrite were linear over the concentration range of 0.01 to 1.0 micromol/mL in
      plasma, and the lower limit of detection for both compounds was 0.005
      micromol/mL. The accuracy and precision of this method were evaluated and
      coefficients of variation were lower than 10.4%. Blood nitrate and nitrite
      concentrations of six victims who committed suicide by inhaling automobile
      exhaust gas could be determined using our method.

PMID- 12220013
TI  - A general screening method for acidic, neutral, and basic drugs in whole blood
      using the Oasis MCX column.
AB  - Solid-phase extraction (SPE) is becoming a commonly used extraction technique.
      Most existing SPE methods extract a single drug from a relatively clean
      biological matrix (e.g., plasma, serum, or urine) using a silica-based column.
      These methods, however, are generally not satisfactory for forensic applications
      because the majority of biological samples are not as clean (e.g., whole blood,
      bile, tissues). Silica-based columns also may have reproducibility and stability
      problems. Polymer-based columns have been developed to overcome some of these
      limitations. In this study, sequential extraction of acidic, neutral, and basic
      drugs from whole blood using a polymer-based column, Oasis MCX, was undertaken.
      The extraction procedure developed involved a conditioning step using methanol
      followed by water; a three-step wash sequence using water, 0.1 M hydrochloric
      acid, then water/methanol (95:5); and two elution steps. One elution step was for
      acidic and neutral drugs utilizing acetone/chloroform (1:1), and a second used
      ethyl acetate/ammonium hydroxide (98:2) for basic drugs. Of the drugs tested, 75%
      were extractable from whole blood and detectable at therapeutic concentrations.
      Good recoveries and clean extracts were achieved for the basic drugs; however,
      the extracts were not as clean for acidic drugs. Unfortunately, the Oasis MCX
      procedure was not suitable for extracting all drugs (e.g., benzodiazepines).

PMID- 12220014
TI  - Reference limits for urine/blood ratios of ethanol in two successive voids from
      drinking drivers.
AB  - Specimens of venous whole blood and two successive urinary voids were collected
      from 450 individuals apprehended for driving under the influence of alcohol in
      Sweden. The first specimen of urine (UAC-1) was obtained as soon as possible
      after arrest, and the second void (UAC-2) was collected about 60 min later (mean
      66 min, range 30-130). A specimen of venous blood was drawn approximately 30 min
      after the first urine sample was collected. Ethanol was determined in blood and
      urine by headspace gas chromatography, a method with high analytical precision
      (coefficient of variation approximately 1%). The mean UAC for the first void was
      2.60 g/L (range 0.21-5.35) compared with 2.40 g/L (range 0.16-5.50) in the second
      void. The mean concentration of alcohol in venous blood (BAC) was 1.97 g/L (range
      0.08-4.57). The concentrations of ethanol in the two voids of urine were highly
      correlated (r = 0.97, residual standard deviation [SD] 0.22 g/L). The UAC and BAC
      results were also highly correlated; r = 0.958 (residual SD 0.28 g/L) for the
      first void and r = 0.978 (residual SD 0.21 g/L) for the second void. The
      concentration of ethanol in the first void (UAC-1) was higher than the second
      void (UAC-2) in 383 (87%) instances, decreasing by 0.23 g/L/h on average. In 57
      instances (13%), UAC-1 was less or equal to UAC-2 with a mean increase of 0.19
      g/L. When BAC exceeded 0.5 g/L (N = 429), the mean UAC-1/BAC ratio was 1.345 with
      95% reference limits of 0.968 and 1.72, which agreed well with median (2.5th and
      97.5th percentiles) of 1.325 (0.938 and 1.79). For the second void, the mean UAC
      2/BAC ratio was 1.221 with 95% reference limits of 0.988 and 1.45 and with a
      median (2.5th and 97.5th percentiles) of 1.226 (0.997 and 1.46). These reference
      limits are appropriate to use when a person's venous BAC needs to be estimated
      with reasonable scientific certainty from the concentration determined in
      specimens of urine.

PMID- 12220016
TI  - Extraction of amphetamine and methamphetamine from urine specimens with Cerex
      Polycrom Clin II solid-phase extraction columns and the Speedisk 48 Pressure
      Processor.
AB  - Extraction of amphetamine and methamphetamine in urine was investigated using
      Cerex Polycrom Clin II solid-phase extraction columns and the Speedisk 48
      Pressure Processor as a replacement for our liquid-liquid procedure. Linearity
      for urine standards extracted with the Cerex-Speedisk method ranged from 50 ng/mL
      for methamphetamine and from 150 ng/mL for amphetamine to 10,000 ng/mL for both.
      The mean recovery at the 500-ng/mL cutoff for three different lots of columns was
      96.4% for AMP and 95.7% for MET. The mean of the within-run means for three
      batches was 495.4 ng/mL with a coefficient of variation (CV) of 1.2% or less for
      amphetamine and 496.4 ng/mL for methamphetamine with a CV of 1.7% or less. Thirty
      six specimens containing amphetamine and the same number for methamphetamine were
      analyzed by both the Cerex-Speedisk and liquid-liquid methods. The correlation
      for specimens containing amphetamine gave an r2 of 0.9986 with a slope of 0.99;
      for methamphetamine, the r2 was 0.9997 with a slope of 0.98. The Cerex-Speedisk
      method cut extraction time in half, was less costly, and greatly reduced the
      volume of hazardous waste.

PMID- 12220015
TI  - Intra- and interindividual variations in urinary concentrations of endogenous
      gamma-hydroxybutyrate.
AB  - This study was designed to determine the urinary concentrations of endogenous GHB
      over a one-week period, the variations that occur within those concentrations,
      and whether those variations are affected by normalization to urinary creatinine.
      Its purpose was to ascertain whether endogenous concentrations fluctuate to such
      an extent that they may be misinterpreted as due to GHB ingestion. Every urine
      void produced by eight GHB-free subjects (five males and three females) over a
      one-week period was individually collected and analyzed for the presence of
      endogenous GHB and creatinine. The results of the non-normalized and normalized
      concentrations were statistically analyzed. Non-normalized GHB concentrations
      ranged from 0.00 to 6.63 microg/mL over seven days. The coefficients of variation
      (CV) for the individual non-normalized data were 44.0% to 77.7%. When the data
      were normalized to creatinine, the concentrations ranged from 0.00 to 6.79
      microg/mg. The CVs for the creatinine-normalized results were between 29.7% and
      76.8%. Analysis of the differences in CVs by the paired t-test (alpha = 0.05)
      found these improvements to be statistically insignificant. Such normalization
      allows for correction of urinary dilution or concentration by the kidneys which
      may affect endogenous GHB concentrations. The data also suggest significant (p <
      0.001) differences in median endogenous urinary concentrations of GHB between
      males and females using the Mann-Whitney test. Because of the small number of
      subjects in this study, further investigations are required to substantiate this
      observation. Some of the subjects in this study demonstrated a strong tendency to
      produce higher or lower GHB concentrations at consistent periods during the day.
      This was most evident when looking at the creatinine-normalized concentrations.
      The results of our study indicate that there are significant intra- and
      interindividual variations in the urinary concentrations of endogenous GHB.
      Furthermore, there are also wide variations between individuals in the total
      daily amount of GHB excreted in the urine. Nonetheless, no specimen's GHB
      concentration approached 10 microg/mL (non-normalized) or 10 microg/mg
      (normalized). This study of the variability in endogenous urinary GHB excretion
      supports the recommendation of 10 microg/mL as an appropriate cutoff to identify
      exogenous GHB exposure in the absence of rare genetic deficiencies such as GHB
      aciduria. Patients with such a deficiency should be readily identifiable through
      prominent symptoms, repeated urinalysis, or genetic testing.

PMID- 12220017
TI  - 1H NMR urine analysis as an effective tool to detect creatine supplementation.
AB  - Creatine is one of the main compounds in muscular energetic metabolism leading to
      phosphocreatine to maintain high ATP levels. Creatine is found in blood and
      excreted in small amounts in urine. Creatine supplementation and athletic
      performances are supposed to be correlated, particularly in intensive and
      intermittent efforts. After oral creatine supplementation, a 1H nuclear magnetic
      resonance (NMR) spectroscopy method was developed for its direct analysis,
      without any pretreament of urine samples. This method can be used to detect any
      supplementation of creatine, a substance prohibited in France. The detection
      limit is 10 micromol/L (1.31 mg/L) and analysis is performed in 10 min. After a
      single oral supplementation of 2.1 g to three subjects, a kinetic investigation
      reveals a maximum concentration of 20 mmol/L (2.62 g/L), observed between 1 and 6
      h after ingestion. This procedure was used to test 13 urine specimens obtained
      from bodybuilders. From the concentrations measured (range: 0.41 to 10.30 mmol/L,
      54 to 1350 mg/L), the doping practices of at least nine athletes could be
      observed. Creatine is not often analyzed in hospital laboratories. This paper
      documents how easily creatine can be determined and quantitated by 1H NMR
      spectroscopy.

PMID- 12220018
TI  - Determination of cobalt in urine by FI-ICP-AES with online preconcentration.
AB  - A method for the preconcentration and determination of cobalt in human urine
      samples was developed. The online preconcentration and determination were
      attained using inductively coupled plasma atomic emission spectromety (ICP-AES)
      coupled to a flow injection (FI) method. Cobalt was retained on an Amberlite XAD
      7 resin as cobalt-2-(5-bromo-2-pyridylazo)-5-diethylaminophenol complex at pH
      9.5. Cobalt was removed from the microcolumn with perchloric acid. A sensitivity
      enhancement factor of 90 was obtained with respect to cobalt determination by ICP
      AES without preconcentration. The value of detection limit for the
      preconcentration method proposed was 25 ng/L. The precision for 10 replicate
      determinations at the 5 mg/L (mean +/- SD, 5.1 +/- 0.14) Co level was 2.7%
      relative standard deviation, calculated from the peak heights obtained. The
      calibration graph preconcentration method for cobalt was linear with a
      correlation coefficient of 0.9994 from approximately 0.25 mg/L up to at least 100
      mg/L. The method was successfully applied to the determination of cobalt in human
      urine samples.

PMID- 12220019
TI  - Application of LC-MS analysis to a colchicine fatality.
AB  - A 73-year-old man developed nausea, vomiting, and diarrhea 20-30 min after
      receiving a 1.0 mg intravenous dose of colchicine for the treatment of severe
      pain due to gouty arthritis in his physician's office. He was hospitalized 8 h
      later, and his condition deteriorated as he developed renal and respiratory
      failure. He subsequently died 10 h later, or a total of 18 h after he received
      the original 1 mg colchicine injection. The patient received a prescription for
      oral 0.6 mg colchicine tablets 8 days previously and consumed eight tablets
      during that period, an average of 0.6 mg/day (42 of 50 tablets remained at the
      time of death). Colchicine concentrations were measured by liquid chromatography
      mass spectrometry in selected ion monitoring mode using positive ionization.
      Chromatography was performed using an Eclipse XDB C8 analytical column (30 mm x
      2.1-mm i.d., 3-microm particle size) and a programmed mobile phase consisting of
      50 mM pH 4 ammonium acetate buffer and acetonitrile. Colchicine concentrations
      were as follows: 50 microg/L in cardiac blood, 10 microg/L in vitreous humor, 575
      microg/kg in liver, 12,000 microg/L in bile, and 4.4 microg in 60 g received
      gastric contents (estimated total gastric contents 100 g). The cause of death was
      ruled to be "acute colchicine toxicity" and the manner of death "accidental."

PMID- 12220020
TI  - Elevated blood lead levels resulting from the ingestion of air rifle pellets.
AB  - There have been numerous reports of lead poisoning resulting from the ingestion
      of foreign bodies. A case involving the ingestion of spent air rifle pellets is
      described. No clinical symptoms were observed, despite the fact that the young
      child exhibited elevated blood lead levels as high as 2.7 micromol/L (56
      microg/dL). X-rays of the child's abdomen confirmed the ingestion of the pellets.
      The patient was treated with laxatives, and the pellets were successfully passed
      over the course of the next few days. Prior to release from the hospital, the
      child's blood lead level had dropped to 1.7 umol/L (35 microg/dL).

PMID- 12220021
TI  - Lethal diltiazem poisoning.
AB  - A 60-year-old man presented to an emergency department 2 h after the ingestion of
      8 g of diltiazem (about 40 slow-release capsules, 200 mg/each) in a suicide
      attempt. The subject was treated with a gastric lavage and activated charcoal;
      then, a temporary transvenous pacing was also inserted. Despite emergency
      pharmacological treatment, the subject died about 20 h after ingestion.
      Postmortem diltiazem and desacetyl-diltiazem concentrations, measured by gas
      chromatography-mass spectrometry, were as follows: 31.1 mg/mL diltiazem and 9.7
      mg/mL desacetyl-diltiazem in blood; 33.1 mg/g diltiazem and 13.7 mg/g desacetyl
      diltiazem in brain; 179.5 mg/g diltiazem and 47.5 mg/g desacetyl-diltiazem in
      lung; 41.8 mg/g diltiazem and 10.1 mg/g desacetyl-diltiazem in heart; 182.1 mg/g
      diltiazem and 47.3 mg/g desacetyl-diltiazem in liver; 49.2 mg/g diltiazem and
      22.6 mg/g desacetyl-diltiazem in kidney; and 294.9 mg/mL diltiazem and 29.4 mg/mL
      desacetyl-diltiazem in bile. It is interesting to note that although several
      cases of acute diltiazem poisoning have been reported in literature, only a few
      were lethal. Diltiazem concentrations found in our case are notably higher than
      those reported in other studies, including those in which diltiazem ingestion
      resulted in the death of the patient. Notably, in many of these latter cases, the
      doses of diltiazem ingested were higher than those taken by our patient.

PMID- 12220022
TI  - Supravalvular mitral stenosis in a cat.
AB  - A 3-year-old, 4-kg, castrated male domestic shorthair cat presented with signs of
      progressive respiratory distress. Thoracic radiographs showed pulmonary edema and
      pleural effusion. Echocardiography revealed a perforate membrane immediately
      above the mitral valve that divided the left atrium into proximal and distal
      chambers. The left auricle was proximal to the dividing membrane and connected to
      the markedly enlarged proximal left atrial chamber, consistent with the diagnosis
      of supravalvular mitral stenosis (SMS). Position of the obstructing membrane
      relative to the left auricle distinguishes SMS from cor triatriatum sinister
      (CTS). In CTS, the left auricle is distal to the dividing membrane and connects
      to the distal left atrial chamber.

PMID- 12220023
TI  - Frequency of isolation and antimicrobial susceptibility patterns of
      Staphylococcus intermedius and Pseudomonas aeruginosa isolates from canine skin
      and ear samples over a 6-year period (1992-1997).
AB  - Staphylococcus intermedius (S. intermedius) was isolated from 88.6% and 49.4% of
      skin and ear samples, respectively, during the years 1992 through 1997, and
      frequency of isolation remained unchanged. More than 95% of all S. intermedius
      isolates were susceptible to cephalothin and oxacillin, providing support for
      empirical treatment of canine skin and ear infections with cephalexin.
      Pseudomonas aeruginosa (P. aeruginosa) was isolated from 7.5% and 27.8% of skin
      and ear samples, respectively. The frequency of isolation from skin samples
      increased over the study period. Because of multidrug-resistant profiles for P.
      aeruginosa isolates, especially for ear isolates, empirical treatment of P.
      aeruginosa infections is not advisable.

PMID- 12220024
TI  - Cutaneous neosporosis during treatment of pemphigus foliaceus in a dog.
AB  - A 4-year-old, intact male rottweiler was presented with a 10-day history of
      papulonodular dermatitis. At the time of presentation, the dog was receiving
      prednisone and azathioprine to treat pemphigus foliaceus. Cutaneous neosporosis
      was diagnosed by immunohistochemistry on skin biopsy specimens and a high serum
      antibody titer to Neospora caninum by Neospora agglutination test. Electron
      microscopy examination of skin specimens further supported the diagnosis.
      Clindamycin therapy, together with withdrawal of immunosuppressive medication,
      resulted in prolonged clinical remission. This report documents cutaneous
      neosporosis in an adult dog and suggests that immunosuppressive therapy might be
      a predisposing factor.

PMID- 12220025
TI  - Clozapine intoxication in a dog.
AB  - Intoxication with clozapine in a dog, suspected from history and clinical signs
      at presentation, was confirmed by demonstration of decreasing serum levels of
      this drug. Clozapine is a tricyclic dibenzodiazepine used for treatment of human
      schizophrenia, and clinical signs of intoxication in humans include tachycardia,
      seizures, muscle fasciculations, agitation, and sialorrhea. This dog showed
      ptyalism, hyperthermia, tachycardia, and was easily excited by tactile or
      auditory stimulation. The calculated peak concentration of clozapine in this dog
      was approximately 6,000 ng/mL, and the elimination half-life (t(1/2)) was 5
      hours. Charcoal administration and supportive care led to a successful outcome in
      this patient.

PMID- 12220026
TI  - Pulmonary thromboembolism associated with Blastomyces dermatitidis in a dog.
AB  - An 8-year-old, male castrated golden retriever presented for cough and increased
      respiratory effort. Radiographs revealed an alveolar pattern in the right caudal
      lung lobe and an opacity at the carina suspected to be enlarged tracheobronchial
      lymph nodes. The disease progressed to involve the right middle lung lobe.
      Cytopathology of a fine-needle aspirate and bronchoalveolar lavage fluid were
      nondiagnostic. Surgical removal of the right caudal lung lobe and biopsy of the
      perihilar lymph nodes revealed pulmonary thromboembolism and reactive lymph
      nodes. The dog died several days postoperatively, and necropsy revealed diffuse
      pulmonary thromboembolism. Additionally, Blastomyces dermatitis organisms were
      identified in a pyogranulomatous mass surrounding the trachea near the carina. In
      an extensive literature search, no reports of pulmonary thromboembolism
      associated with blastomycosis were identified. It is suspected that the
      inflammation secondary to blastomycosis caused the thromboembolism.

PMID- 12220027
TI  - Use of recombinant tissue-plasminogen activator in a dog with chylothorax
      secondary to catheter-associated thrombosis of the cranial vena cava.
AB  - A 4-year-old, castrated male Maltese developed cranial vena caval thrombosis and
      chylothorax following central venous catheterization for treatment of
      postoperative sepsis. Vena caval thrombolysis was attempted using recombinant
      human tissue-plasminogen activator (t-PA). Thrombolytic therapy led to an acute
      reduction in the size of the caval thrombus and was followed by prompt resolution
      of the chylothorax. Hemorrhage at the entry sites of a jugular catheter and
      esophagostomy tube placed at the time of treatment was a dose-limiting
      complication of t-PA therapy in this dog.

PMID- 12220028
TI  - Muscle cramps in two standard poodles with hypoadrenocorticism.
AB  - Two standard poodles were evaluated for painful, episodic muscle cramps affecting
      their thoracic and pelvic limbs. Both dogs had been diagnosed with
      hypoadrenocorticism and were being treated with fludrocortisone acetate and
      prednisone when evaluated for muscle cramps. However, the muscle cramping started
      approximately 1 month prior to the diagnosis of hypoadrenocorticism. Findings on
      general physical examination included lethargy and dehydration. Neurological
      examination was normal between episodes. Serum biochemical abnormalities included
      hyperalbuminemia, azotemia, hyponatremia, hypochloremia, and hyperkalemia.
      Altering treatment to desoxycorticosterone pivalate resolved the electrolyte
      abnormalities and the episodes of muscle cramping in both dogs. The authors
      conclude that hypoadrenocorticism can be associated with episodes of painful
      muscle cramping in standard poodles.

PMID- 12220029
TI  - Four fraction palliative radiotherapy for osteosarcoma in 24 dogs.
AB  - Twenty-four dogs underwent palliative radiotherapy consisting of four 8 gray (Gy)
      fractions of 60Co radiation on days 0, 7, 14, and 21 at 26 sites for axial (n=11)
      or appendicular (n=15) osteosarcoma. Response was noted in 92% of sites treated.
      Seventeen dogs were euthanized due to local or metastatic disease, one dog died
      of metastatic disease, five dogs died of unrelated causes, and one dog is alive.
      The four fraction protocol is effective for palliation of clinical signs
      associated with axial or appendicular osteosarcoma and may result in a higher
      response rate and longer survival time than three fraction palliative protocols.

PMID- 12220030
TI  - Angiographic study and therapeutic embolization of soft-tissue fibrosarcoma in a
      dog: case report and literature.
AB  - A case of soft-tissue fibrosarcoma with pulmonary metastases in a dog is
      reported. Although three attempts of fine-needle aspiration (FNA) biopsy failed
      to provide definitive tumor diagnosis, results of angiography strongly indicated
      a soft-tissue sarcoma. Transcatheter arterial embolization (TAE) using particles
      of gelatin sponge was performed following selective angiography. The mass was
      decreased in size on reevaluation 2 weeks after embolization. The dog was
      euthanized on the request of the owners due to overall failing health. Necropsy
      and pathological study confirmed the diagnosis of soft-tissue fibrosarcoma with
      pulmonary metastases. In a review of the literature, angiographic findings of
      soft-tissue sarcoma in the dog of this report were similar to those in human
      beings, suggesting a potential role for angiography in the differential diagnosis
      of suspect soft-tissue fibrosarcomas and for guiding FNA or surgical biopsy.
      Previous reports have also shown therapeutic embolization to be an effective
      treatment both in experimental animal study and in clinical practice in the
      human; therefore, TAE could be an effective adjunctive treatment of soft-tissue
      fibrosarcoma in the dog.

PMID- 12220031
TI  - Prognosis following surgical excision of canine cutaneous mast cell tumors with
      histopathologically tumor-free versus nontumor-free margins: a retrospective
      study of 31 cases.
AB  - The purpose of this study was to determine if the presence of histopathologically
      tumor-free versus nontumor-free margins was prognostic for relapse or tumor
      related death in dogs following surgical excision of single or multiple cutaneous
      mast cell tumors confined to the skin without evidence of metastasis to lymph
      nodes or other noncutaneous sites. Differences in tumor-related death or
      frequency of relapse between the two groups were not significant. Failure to
      achieve histopathological tumor-free margins frequently did not lead to local
      relapse. All tumor-related deaths occurred following local relapse. The lack of
      statistical support for an association between prognosis and histopathological
      tumor-free versus nontumor-free margins may be a result of small sample size.

PMID- 12220032
TI  - Breed susceptibility for developmental orthopedic diseases in dogs.
AB  - A large-scale epidemiological study was conducted to determine breeds at risk for
      12 developmental orthopedic diseases (DODs). Developmental orthopedic diseases
      investigated included canine hip dysplasia (CHD); craniomandibular osteopathy
      (CMO); fragmented coronoid process; hypertrophic osteodystrophy; Legg-Calve
      Perthes disease; osteochondrosis of the medial humeral condyle, caudal humeral
      head, femoral condyles, and talar trochlear ridges; panosteitis; patella
      luxation; and ununited anconeal process. Dogs that were diagnosed with any one of
      the diseases of interest at any of 10 veterinary teaching hospitals participating
      in the Veterinary Medical Database from 1986 to 1995 were included as cases. Odds
      ratios and corresponding 95% confidence intervals were calculated to determine
      risk. Frequency of diagnosis during the 10-year period ranged from 35 cases (CMO)
      to 10,637 cases (CHD). The number of breeds at increased risk for a disease
      ranged from one (CMO) to 35 (CHD). Breed susceptibility for a DOD may suggest a
      genetic component in the disease etiology. The results of this study serve to
      increase veterinarians' awareness of breeds susceptible to DODs and may
      facilitate the control of such diseases by identifying breeds that might benefit
      from breeding programs or environmental intervention such as dietary
      modification.

PMID- 12220033
TI  - Emphysematous prostatitis and carcinoma in a dog.
AB  - A 10-year-old, male beagle was presented for lethargy, anorexia, and straining to
      urinate. A mass was palpated in the caudal abdomen in the area of the bladder.
      Abdominal radiography revealed a gas-filled mass in the caudoventral abdominal
      quadrant. Subsequent positive-contrast cystography revealed that the mass was
      caudal to the bladder. Abdominal exploratory celiotomy resulted in the drainage
      of a prostatic abscess containing gas. The histopathological diagnosis of the
      prostate was a poorly differentiated tubular carcinoma with necrosis. To the
      authors' knowledge, this article is the first report of an emphysematous
      prostatitis in a dog.

PMID- 12220034
TI  - When to neuter dogs and cats: a survey of New York state veterinarians' practices
      and beliefs.
AB  - Practicing veterinarians in small-animal or mixed-animal practice in New York
      state were surveyed about their beliefs and practices regarding the age at which
      dogs and cats should be neutered and their attitudes toward early neutering (at 4
      months of age or younger). The majority of veterinarians routinely recommended
      neutering for all client animals (70.6%) and supported the routine neutering of
      shelter animals before adoption (90.3%). More veterinarians in this study
      reported at least one perceived benefit (91.3%) for early neutering than reported
      at least one perceived risk (84.4%). Veterinarians with experience neutering
      early were less likely to believe that the procedure was associated with one or
      more risks.

PMID- 12220036
TI  - Time: the most precious commodity.

PMID- 12220035
TI  - Two conceptions of science.

PMID- 12220037
TI  - The Institute of Neurosciences, Mental Health and Addiction.

PMID- 12220038
TI  - Factors other than the Duke criteria associated with infective endocarditis among
      injection drug users.
AB  - BACKGROUND: Modified Duke criteria were applied to consecutive injection drug
      users (IDUs) who were admitted to an inner-city hospital with a clinical
      suspicion of infective endocarditis, and the presence of any other clinical
      variables that were predictive of the presence of infective endocarditis was
      determined. METHODS: Clinical data on consecutive IDUs who were hospitalized over
      15 months in Vancouver were collected. Data included the admission history, and
      findings on physical examination and on initial laboratory investigations. Each
      subject's course in hospital was followed until discharge or death during the
      index hospitalization. Follow-up data collected included culture results, the
      interpretation of the echocardiogram and the discharge diagnosis. The modified
      Duke criteria were used for the diagnosis of infective endocarditis (definite,
      possible or rejected). Multiple logistic regression was used to determine what
      clinical variables (exclusive of the Duke criteria) available within 48 hours of
      presentation were independent predictors of infective endocarditis. RESULTS: One
      hundred IDUs were enrolled. Fifty-one were female, and 58 were HIV-positive.
      Twenty-three met the modified Duke criteria for definite infective endocarditis,
      and 25 had possible infective endocarditis. IDUs with definite infective
      endocarditis were more commonly noted to have evidence of vascular phenomena
      (arterial embolism, septic pulmonary infarction, mycotic aneurysm, intracranial
      hemorrhage or Janeway lesions) (6 [26%]) than those who had possible endocarditis
      (1 [4%]). Those with definite infective endocarditis more often had multiple
      opacities on chest radiography (56% v. < 12%), and fewer had an obvious source of
      infection (52% v. 72% and 81% of possible and rejected infective endocarditis,
      respectively). Among febrile IDUs, definite endocarditis was highly associated
      with having no obvious source of infection (odds ratio 3.1 [95% confidence
      interval 1.1-8.7]) compared with febrile IDUs with an obvious source of
      infection. In similarly compared groups, the presence of hematuria, proteinuria
      or pyuria was also predictive of definite endocarditis (odds ratio 2.9 [95% CI
      1.1-8.6]). CONCLUSIONS: Among IDUs, the modified Duke criteria are useful for
      classifying cases with definite infective endocarditis and rejecting cases
      without infective endocarditis. The classification of possible infective
      endocarditis is suitable for this population.

PMID- 12220039
TI  - The detection and management of abdominal aortic aneurysm: a cost-effectiveness
      analysis.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) is an important cause of death in
      Canada, and about 80% of the deaths are due to ruptured aneurysm. METHOD: To
      determine the most cost-effective way of controlling AAA in terms of early
      detection and clinical management, a cohort analysis was undertaken beginning at
      age 50 years, using a multistate life-table model with parameters derived from
      published articles. The model was used to determine (a) the optimum size for
      elective surgery and (b) the optimum rate of detection of intact AAA. Cost per
      quality-adjusted life-year (QALY) was used to measure outcome. RESULTS: The most
      cost-effective diameter for repair of an intact AAA increases with age between
      the limits of 55 and 70 mm. The predominant size for repair is 60 mm. The most
      cost-effective rate at which latent AAA should be detected is 20% per year,
      corresponding to a screening interval of 5 years. Selective screening by sex or
      smoking status, or both, does not improve cost-effectiveness. CONCLUSIONS:
      Primary care patients aged 50 years and over should be offered abdominal
      ultrasonography every 5 years. Those with AAA should be kept under surveillance
      and offered elective surgery when the aneurysm reaches 60 mm in diameter.

PMID- 12220040
TI  - Echocardiography in right-sided endocarditis.

PMID- 12220041
TI  - What did Edward Jenner and John Tyndall have in common?

PMID- 12220042
TI  - Is osteoarthritis a genetic disease?
AB  - Osteoarthritis (OA) is a common, disabling condition of diarthrodial joints. For
      over 60 years there has been evidence that inherited factors are important in its
      etiology. The research to identify these genetic factors has been driven by the
      need to establish markers of disease onset and progression to help clinical
      management and by the need to discover new disease targets for drug design. Both
      candidate gene studies and genome wide scanning have been undertaken and have
      provided some important initial results, which are considered in this review. How
      the research to identify OA susceptibility genes will progress and the use of new
      technologies to facilitate this are discussed.

PMID- 12220043
TI  - Children's perceptions of popular and unpopular peers: a multimethod assessment.
AB  - Children's perceptions of popular and unpopular peers were examined in 2 studies.
      Study 1 examined the degree to which 4th-8th-grade boys and girls (N = 408)
      nominated the same peers for multiple criteria. Children viewed liked others as
      prosocial and disliked others as antisocial but associated perceived popularity
      with both prosocial and antisocial behavior. In Study 2, a subset of the children
      from Study 1 (N = 92) described what makes boys and girls popular or unpopular.
      Children described popular peers as attractive with frequent peer interactions,
      and unpopular peers as unattractive, deviant, incompetent, and socially isolated.
      In both studies, children's perceptions varied as a function of the gender, age,
      and ethnicity of the participants.

PMID- 12220045
TI  - Maternal stress and affect influence fetal neurobehavioral development.
AB  - The authors investigated the association between maternal psychological and fetal
      neurobehavioral functioning. Data were provided by 52 maternal-fetal pairs at 24,
      30, and 36 weeks gestation. The relations between maternal measures and fetal
      heart rate, variability, and motor activity were statistically modeled. Fetuses
      of women who were more affectively intense, appraised their lives as more
      stressful, and reported more frequent pregnancy-specific hassles were more active
      across gestation. Fetuses of women who perceived their pregnancy to be more
      intensely and frequently uplifting and had positive emotional valence toward
      pregnancy were less active. Associations with fetal heart-rate measures were
      detected at 36 weeks gestation. These data provide evidence for proximal effects
      of maternal psychological functioning on fetal neurobehavior.

PMID- 12220044
TI  - Children's intellectual and emotional-behavioral adjustment at 4 years as a
      function of cocaine exposure, maternal characteristics, and environmental risk.
AB  - The authors examined 223 children at age 4 years for the effects of prenatal
      cocaine exposure, exposure to other substances, maternal and environmental risk
      factors, and neonatal medical problems on IQ, externalizing problems, and
      internalizing problems. Regression analyses showed that maternal verbal IQ and
      low environmental risk predicted child IQ. Cocaine exposure negatively predicted
      children's overall IQ and verbal reasoning scores, but only for boys. Cocaine
      exposure also predicted poorer short-term memory. Maternal harsh discipline,
      maternal depressive symptoms, and increased environmental risk predicted
      externalizing problems. In contrast, only maternal depressive symptoms predicted
      internalizing problems. These findings indicate that early exposure to substances
      is largely unrelated to subsequent IQ or adjustment, particularly for girls.

PMID- 12220046
TI  - Risk factors for body dissatisfaction in adolescent girls: a longitudinal
      investigation.
AB  - Because few prospective studies have examined predictors of body dissatisfaction-
      an established risk factor for eating disorders--the authors tested whether a set
      of sociocultural, biological, interpersonal, and affective factors predicted
      increases in body dissatisfaction using longitudinal data from adolescent girls
      (N = 496). Elevated adiposity, perceived pressure to be thin, thin-ideal
      internalization, and social support deficits predicted increases in body
      dissatisfaction, but early menarche, weight-related teasing, and depression did
      not. There was evidence of 2 distinct pathways to body dissatisfaction--1
      involving pressure to be thin and 1 involving adiposity. Results support the
      contention that certain sociocultural, biological, and interpersonal factors
      increase the risk for body dissatisfaction, but suggest that other accepted risk
      factors are not related to this outcome.

PMID- 12220047
TI  - Assessing secure base behavior in adulthood: development of a measure, links to
      adult attachment representations, and relations to couples' communication and
      reports of relationships.
AB  - A focus on the secure base phenomenon creates a framework for exploring the
      function of the attachment system in adulthood. Engaged couples (N = 157) were
      videotaped in a problem-solving interaction and assessed using the Secure Base
      Scoring System (SBSS), a system based on Ainsworth's analyses of infant-parent
      secure base use and support. Study 1 showed behavior was significantly related to
      representations assessed with the Adult Attachment Interview (M. Main & R.
      Goldwyn, 1994). In Study 2, the interactions were independently scored with the
      Rapid Marital Interaction Coding System (RMICS; R. E. Heyman & D. Vivian, 1993),
      a communication-based system. The SBSS predicted relationship variables beyond
      the RMICS, especially for women. Results indicate that the secure base phenomenon
      provides a cogent perspective on adult attachment behavior.

PMID- 12220048
TI  - Maternal relationship instability and the school behavior of children from
      disadvantaged families.
AB  - This longitudinal study examined the relation between the instability of maternal
      intimate relationships and the school behavior of 3rd-grade children from
      economically disadvantaged families. After ecological correlates were controlled,
      chronic relationship instability predicted externalizing behavior for boys and
      girls and internalizing behavior for girls, but not academic competence. In
      addition, past and recent instability had independent effects: Recent instability
      moderated the relation for past instability, and child adjustment in highly
      unstable families varied with verbal ability and aspects of the family ecology.
      The theoretical implications concern conceptualizations of the diverse and
      dynamic nature of family arrangements experienced by disadvantaged children.

PMID- 12220049
TI  - False memories in children and adults: age, distinctiveness, and subjective
      experience.
AB  - This study investigated developmental trends associated with the Deese/Roediger
      McDermott false-memory effect, the role of distinctive information in false
      memory formation, and participants' subjective experience of true and false
      memories. Children (5- and 7-year-olds) and adults studied lists of semantically
      associated words. Half of the participants studied words alone, and half studied
      words accompanied by pictures. There were significant age differences in recall
      (5-year-olds evinced more false memories than did adults) but not in recognition
      of critical lures. Distinctive information reduced false memory for all age
      groups. Younger children provided with distinctive information, and older
      children and adults regardless of whether they viewed distinctive information,
      expressed higher levels of confidence in true than in false memories. Source
      attributions did not significantly differ between true and false memories.
      Implications for theories of false memory and memory development are discussed.

PMID- 12220050
TI  - Family processes as pathways from income to young children's development.
AB  - A variety of family processes have been hypothesized to mediate associations
      between income and young children's development. Maternal emotional distress,
      parental authoritative and authoritarian behavior (videotaped mother-child
      interactions), and provision of cognitively stimulating activities (Home
      Observation for Measurement of the Environment [HOME] scales) were examined as
      possible mediators in a sample of 493 White and African American low-birth-weight
      premature infants who were followed from birth through age 5. Cognitive ability
      was assessed by standardized test, and child behavior problems by maternal
      report, when the children were 3 and 5 years of age. As expected, family income
      was associated with child outcomes. The provision of stimulating experiences in
      the home mediated the relation between family income and both children's
      outcomes; maternal emotional distress and parenting practices mediated the
      relation between income and children's behavior problems.

PMID- 12220052
TI  - The structure of language abilities at 4 years: a twin study.
AB  - Normal language development was studied in 310 pairs of 4-year-old twins born in
      the United Kingdom in 1994. Twins were assessed individually in their homes on a
      diverse battery of language and nonverbal measures. Rotated factor analyses
      indicated the presence of a general Language factor (L) as well as a general
      Nonverbal (NV) factor. Moderate genetic influence was found for both L and NV
      abilities. Bivariate genetic analysis estimated a genetic correlation of .63
      between L and NV abilities, implying that over half of the genetic influence on L
      overlaps with genetic influence on NV. These results suggest that at age 4,
      genetic influences on individual differences in language overlap substantially
      with genetic influences on individual differences in other cognitive abilities,
      although perhaps less so than later in development.

PMID- 12220051
TI  - Processes linking weight status and self-concept among girls from ages 5 to 7
      years.
AB  - This study assessed the relationship between girls' weight status and self
      concept and examined peer teasing and parent criticism as potential mediators of
      this relationship. Data were collected for 182 girls and their parents when the
      girls were 5 and 7 years old. At each age, girls' body mass index, self-concept,
      peer weight-related teasing (child report), and parents' criticism of girls'
      weight status (spouse report) were assessed. At ages 5 and 7, girls who were more
      overweight reported lower self-concept. Peer teasing and parent criticism
      mediated the relationship between weight status and self-concept at age 7, but
      not at age 5. In addition, the duration and timing of parent criticism across
      ages 5 and 7 mediated the association between girls' weight status at age 5 and
      perceived peer acceptance at age 7.

PMID- 12220053
TI  - Maternal employment and infant-mother attachment security at 12 months
      postpartum.
AB  - This study assessed the association between aspects of mother's employment and
      security of infant-mother attachment, in combination with proximal (maternal
      sensitivity) and distal (demographic, maternal, child, child-care) factors.
      Participants were 145 Australian mothers and their firstborn children. Attachment
      security was assessed with the Strange Situation at 12 months. Results showed
      that mothers' prenatal attitudes to work and timing of the return to work made
      significant, independent contributions to attachment outcomes over and above the
      effects of proximal and distal predictors. Mothers who expressed more commitment
      to work and less anxiety about using nonfamily child care, and who returned to
      work earlier, were more likely to have secure infants. These findings are
      considered in relation to contemporary expectations about mothers' participation
      in paid work and other predictors of secure attachment.

PMID- 12220054
TI  - Marital conflicts in the home when children are present versus absent.
AB  - Characteristics of marital conflict when children (8-16 years) were present
      versus absent were compared on the basis of 47 mothers' and fathers' reports
      during a 15-day period. Mothers described 669 incidents of marital conflict, and
      fathers described 551 incidents. About two thirds of the conflicts occurred in
      children's absence. Contrary to predictions, conflicts in which children were
      present were more negative (e.g., more negative emotions, more destructive
      conflict tactics) and more often about children than were child-absent conflicts.
      Although parents may attempt to protect children from conflict exposure, children
      tend to be exposed to a relatively hostile and emotionally negative subset of the
      marital conflicts that occur in the home.

PMID- 12220055
TI  - Effects of early experience on children's recognition of facial displays of
      emotion.
AB  - The present research examines visual perception of emotion in both typical and
      atypical development. To examine the processes by which perceptual mechanisms
      become attuned to the contingencies of affective signals in the environment, the
      authors measured the sequential, content-based properties of feature detection in
      emotion recognition processes. To evaluate the role of experience, they compared
      typically developing children with physically abused children, who were presumed
      to have experienced high levels of threat and hostility. As predicted, physically
      abused children accurately identified facial displays of anger on the basis of
      less sensory input than did controls, which suggests that physically abused
      children have facilitated access to representations of anger. The findings are
      discussed in terms of experiential processes in perceptual learning.

PMID- 12220056
TI  - Home sweet home(s): parental separations, residential moves, and adjustment
      problems in low-income adolescent girls.
AB  - Associations between histories of family disruption (residential moves and
      separations from parent figures) and adolescent adjustment (including
      educational, internalizing, externalizing, and sexual behavior outcomes) were
      examined in a random sample of 267 African American girls from 3 urban poverty
      neighborhoods. Higher numbers of residential moves and parental separations
      significantly predicted greater adolescent adjustment problems after household
      demographic characteristics were controlled. Adolescents' perceptions of their
      current relationships and neighborhoods were significantly associated with
      adolescent adjustment but did not mediate the effects of family disruption.
      Associations between parental separations and adolescent outcomes were strongest
      for externalizing problems and were found for both male and female caregivers,
      for long-standing and more temporary caregivers, and for separations in early
      childhood, middle childhood, and adolescence.

PMID- 12220057
TI  - Maternal sensitivity, infant attachment, and temperament in early childhood
      predict adjustment in middle childhood: the case of adopted children and their
      biologically unrelated parents.
AB  - In a longitudinal study, internationally adopted children (N = 146) placed before
      6 months of age were followed from infancy to age 7. Results showed that girls
      were better adjusted than boys, except in cognitive development, and that easy
      temperament was associated with higher levels of social, cognitive, and
      personality development and fewer behavior problems. Higher quality of child
      mother relationships, in terms of attachment security and maternal sensitivity,
      uniquely predicted better social and cognitive development. The combination of
      attachment disorganization and difficult temperament predicted less optimal ego
      control and lower levels of cognitive development. It is concluded that even in
      adopted children, who are not biologically related to their adoptive parents,
      early mother-infant interactions and attachment relationships predict later
      socioemotional and cognitive development, beyond infant temperament and gender.

PMID- 12220058
TI  - Getting by with a little help from self and others: self-esteem and social
      support as resources during early adolescence.
AB  - Influences of social support and self-esteem on adjustment in early adolescence
      were investigated in a 2-year longitudinal study (N = 350). Multi-informant data
      (youth and parent) were used to assess both overall levels and balance in peer-
      versus adult-oriented sources for social support and self-esteem. Findings
      obtained using latent growth-curve modeling were consistent with self-esteem
      mediating effects of social support on both emotional and behavioral adjustment.
      Lack of balance in social support and self-esteem in the direction of stronger
      support and esteem from peer-oriented sources predicted greater levels and rates
      of growth in behavioral problems. Results indicate a need for process-oriented
      models of social support and self-esteem and sensitivity to patterning of sources
      for each resource relative to adaptive demands of early adolescence.

PMID- 12220059
TI  - Infants' behavioral reenactment of "failed attempts": exploring the roles of
      emulation learning, stimulus enhancement, and understanding of intentions.
AB  - Two studies were conducted to examine whether infants' reenactment of intended
      but unconsummated acts in A. N. Meltzoff's (1995) failed-attempt paradigm is due
      to reading the adult's underlying intention or to the effects of nonimitative
      social learning processes. Two novel conditions that emphasized the object
      affordances and the spatial contiguity of the object sets were devised. When
      infants' first actions only were counted, infants who observed the full
      demonstration model produced more target acts. When all target acts produced
      within the 20-s response period were counted, infants in the emulation-learning
      and spatial contiguity conditions produced as many target acts as infants in the
      full-demonstration and failed-attempt conditions. This pattern of findings
      suggests that nonimitative social learning processes may influence infants'
      response in the behavioral reenactment paradigm.

PMID- 12220060
TI  - Family obligation and the transition to young adulthood.
AB  - Changes in a sense of obligation to assist, support, and respect the family were
      examined among an ethnically diverse group of 745 American individuals as they
      began to move from secondary school into young adulthood. A sense of family
      obligation increased for all young adults, with slight variations according to
      ethnic and financial backgrounds. Young adults from Filipino and Latin American
      families reported the strongest sense of familial duty during young adulthood,
      which partially explained their tendency to live with and contribute financially
      to their families. The implications of family obligation for employment and
      educational persistence depended on age and academic performance in high school.
      Finally, a sense of family obligation was associated with more positive emotional
      well-being.

PMID- 12220061
TI  - Applications of magnetic resonance imaging for diagnosing thoracic aortic
      diseases.

PMID- 12220062
TI  - Brain protection during surgery of the aortic arch.
AB  - Deep hypothermia with circulatory arrest is the usual method of cerebral
      protection during replacement of the aortic arch. It has the enormous advantage
      of allowing the surgical repair to be carried out in a complete bloodless field
      with no aortic cross-clamping. However, this method only gives the surgeon a
      limited period of time to carry out the aortic repair. It also requires that
      cardiopulmonary bypass be prolonged to cool and rewarm the patient which may be
      the cause of various complications. It has been proposed to improve the
      efficiency and the results of deep hypothermia, by associating it with retrograde
      cerebral perfusion of the brain with oxygenated blood through the superior vena
      cava. This technique improves the tolerance of the brain to cold ischemia and
      increases the time of repair allowed to the surgeon. Antegrade selective cerebral
      perfusion has also been in use for more than three decades. When the perfusion is
      derived from the main arterial line and performed at moderate hypothermia, the
      aorta must be cross-clamped to perform the repair. In addition, there is some
      uncertainty as to what constitutes adequate perfusion flow at normal or moderate
      hypothermic conditions. To reconcile the advantages of both approaches while
      avoiding their major drawbacks, in 1986 we proposed an original method of
      selective antegrade brain perfusion. The principle is to perfuse selectively the
      brain with cold blood (10 to 12 degrees C) while maintaining the central
      temperature in moderate hypothermia (25-28 degrees C). During the time of the
      distal anastomosis the cardiopulmonary bypass is stopped, maintaining only the
      cerebral perfusion at a flow rate of about 400 to 500 mL/mn and a pressure of
      about 70 mmHg. As soon as the distal anastomosis is completed the main perfusion
      is resumed. Two hundred and six patients with a mean age of 57 years (22 to 83)
      were operated on with this technique between October 1984 and March 2001. One
      hundred forty three patients underwent an elective procedure and 63 patients were
      operated on in emergency, mainly for acute type A dissection (54 of 63). The
      hospital mortality was 17% (34 patients). Death was directly related to
      neurological injury in 9 patients (4.4%). All others patients awoke within 6 to 8
      hours and were conscious at 24 hours postoperatively. Thirteen nonfatal
      neurological complications were observed. The type of lesion, gender, age,
      duration of CPB, cerebral perfusion, and circulatory arrest had no influence on
      the neurological outcome of the patients. In our experience, antegrade selective
      perfusion of the brain with cold blood and moderate hypothermic central
      temperature constitutes the method of choice for cerebral protection during
      surgery of the aortic arch as it requires no prolonged CPB and does not limit the
      time available to perform the aortic repair.

PMID- 12220064
TI  - Guidelines for the diagnosis and surgical treatment of diseases of the aorta.

PMID- 12220063
TI  - The use of an intraluminal aortic ring for treatment of diseases of the aorta: 13
      year experience.

PMID- 12220065
TI  - The concept of interventional therapy in acute aortic syndrome.

PMID- 12220066
TI  - Closing perimembranous ventricular septal defects in adult patients in the
      beating heart.
AB  - OBJECTIVE: Although the incidence of complete heart block and residual shunt
      following closure of ventricular septal defects is very low in modern series, the
      risk of these complications still exists. Closing the inferior margin of a
      perimembranous VSD in the beating heart, may in some cases, be a safe technique
      which eliminates the risk of atrioventricular block and residual shunt. METHODS:
      In 17 patients operated on for isolated VSD (Group I), the inferior margin of the
      defect was closed in the beating heart. The results of this technique have been
      compared with another 158 patients (Group II) in whom the VSD was closed under
      cardioplegic arrest. RESULTS: In Group I complete atrioventricular block
      developed during the placing or tying down of the sutures in 2 patients (11.7%).
      Normal sinus rhythm returned in 2 minutes following removing and replacement.
      Additional sutures were placed for residual shunt in 3 patients (17.6%). Of the
      158 patients in Group II, there was complete atrioventricular block in 12 (7.5%)
      in the early postoperative period, and 4 (2.5%) later required a permanent
      pacemaker. Endocarditis prophylaxis was given to 13 patients (8.2%) because of
      hemodynamically insignificant residual shunts. Three patients (1.9%) were
      reoperated for a significant shunt. CONCLUSIONS: Closing the inferior margin of a
      perimembranous VSD in the beating heart is a safe technique which eliminates the
      risk of atrioventricular block and residual shunt.

PMID- 12220067
TI  - Preserved atrial response to dobutamine stress after the modified maze procedure
      for chronic atrial fibrillation: echocardiographic assessment of atrial function.
AB  - BACKGROUND: The maze operation is effective in varying degrees for the
      restoration of atrial function at rest. However, the atrial mechanical function
      under stressed conditions has not been investigated. METHODS: Thirteen patients
      who regained normal sinus rhythm after the modified maze procedure for atrial
      fibrillation (Af) associated with valvular disease were enrolled in this study. A
      two-staged, low-dose protocol (at doses of 5 and 10 microg/kg/min) of dobutamine
      stress echocardiography (DSE) was performed to assess the probability of the
      appearance of atrial wave in 20 consecutive beats (Paw), the velocity of atrial
      filling wave (Av), and the early filling wave (Ev) with their ratio (A/E), as
      well as the left atrial area fraction (LAAF) which represents an ejection
      fraction of the left atrium. RESULTS: Under resting conditions, Paw was 72% and
      50% at tricuspid (T) and mitral (M) position, respectively. During dobutamine
      stress (5 microg/kg/min), Paw tended to increase both at T and M position (86%
      and 60%, respectively). Av was significantly accelerated by dobutamine stress (10
      microg/kg/min) in both T (from 0.36 to 0.54 m/s) and M (from 0.46 to 0.69 m/s)
      valvular flow, which was accompanied by a significant increase in A/E (from 0.69
      and 0.31 to 0.87 and 0.40, respectively). Although heart rate was significantly
      increased during dobutamine stress, LAAF remained at the same level (0.18, 0.22
      and 0.19 at rest, 5 and 10 microg/kg/min) and atrial output was expected to be
      enhanced by dobutamine stress. CONCLUSION: Restoration of atrial mechanical
      function after the maze operation is accompanied by preserved response to
      dobutamine stress.

PMID- 12220069
TI  - Dextrocardia: technical aspects of reoperative aortic and tricuspid valve
      replacement.
AB  - Tricuspid and aortic valve replacement was performed on a 50-year old man with
      dextrocardia, situs solitus, D-ventricular looping, and normally related great
      arteries. Twenty-two years earlier the patient had undergone repair of an
      incomplete atrioventricu lar canal and mitral valve replacement. The anatomic
      issues and operative considerations are discussed for aortic and tricuspid valve
      replacement in this anatomic situation with special emphasis on tricuspid valve
      replacement through a right ventriculotomy. Six months after surgery, New York
      Heart Association functional class improved from class III preoperatively, to
      class II.

PMID- 12220068
TI  - A rat model of ischemic cardiomyopathy for investigating left ventricular volume
      reduction surgery.
AB  - OBJECTIVE: The effects of volume reduction surgery (VRS) for ischemic
      cardiomyopathy are not fully understood. The development of a proper animal model
      will help to resolve this issue. METHODS: Study 1 (Noninvasive study): Twenty-six
      rats developed large akinetic left ventricular (LV) aneurysms or ischemic
      cardiomyopathy after anterior descending artery ligation (first surgery). Four
      weeks after the surgery, 13 rats underwent volume reduction surgery (second
      surgery) (VRS group), while 13 underwent rethoracotomy alone (sham group). Before
      the first surgery, and before and after the second surgery, the LV dimensions
      were measured by echocardiography, and the heart rate and systolic blood pressure
      were recorded by the tail cuff method. Study 2 (Invasive study): In 7 rats
      undergoing the VRS and 9 undergoing the sham operation, LV pressure was measured
      with a manometer-tipped catheter, immediately before and after the second
      surgery. RESULTS: Study 1: All rats survived the second surgery, after which LV
      end-diastolic diameter decreased and LV fractional shortening increased (both p <
      0.001) in the VRS group. This group also increased heart rate after the second
      surgery (p < 0.05). Study 2: There were no differences in LV end-systolic or end
      diastolic pressure between the two groups before and after the second surgery.
      CONCLUSIONS: This model enables reproducible physiological evaluation of the LV
      after VRS, and since the rats show postoperative survival, it provides a useful
      tool for various investigations.

PMID- 12220071
TI  - Beating-heart valvular surgery: a possible alternative for patients with severely
      compromised ventricular function.
AB  - Cardioplegic arrest of the severely compromised ventricle may make weaning from
      cardiopulmonary bypass problematic. We report a novel approach to myocardial
      protection in a patient requiring multi-valve surgery who had an ejection
      fraction of 15%. Warm oxygenated blood was infused continuously both antegrade
      and retrograde during aortic valve replacement and mitral and tricuspid valve
      repair. Adequacy of perfusion was confirmed by the absence of
      electrocardiographic changes. Clinical improvement suggests that this strategy of
      myocardial protection warrants further investigation.

PMID- 12220070
TI  - Partial anomalous pulmonary venous connection: correction by intra-atrial baffle
      and cavo-atrial anastomosis.
AB  - The creation of intracaval conduits to repair partial anomalous pulmonary venous
      connection of the right lung into the superior vena cava can be complicated by
      arrhythmias and superior vena cava and pulmonary vein obstruction. An intra
      atrial baffle, combined with cavo-atrial anastomosis, has been proposed to avoid
      these complications. The authors report their recent experience with this
      operative technique. From January 1997 to December 2000, 7 patients with a mean
      age of 13.5 +/- 9 (2-31) years were operated according to this technique. Only
      one child did not have an associated atrial septal defect. The mean number of
      pulmonary veins connected to the superior vena cava was 2.5 +/- 0.5. The
      immediate postoperative course was uneventful for the seven patients. The mean
      follow-up was 20 +/- 17 months. No patient developed arrhythmia or superior vena
      cava or pulmonary vein obstruction at echocardiography. This surgical technique
      appears to constitute an attractive alternative when pulmonary veins drain
      abnormally into the superior vena cava above the cavo-atrial junction.

PMID- 12220072
TI  - Surgical treatment of congenital coronary artery fistulas: 27 years' experience
      and a review of the literature.
AB  - BACKGROUND AND AIM OF THE STUDY: A congenital coronary artery fistula (CAF) is a
      relatively rare congenital anomaly and is defined as an abnormal direct
      communication between any coronary artery and any of the cardiac chambers. This
      article reviews our experience over the past 27 years, as well as other
      literature, and discusses the surgical indications and methods relating to CAF.
      METHODS: From 1973, 25 patients aged from 2 to 69 years underwent surgical
      treatment for congenital CAF. Seventeen patients were diagnosed as isolated CAF.
      All patients under 19 years of age with isolated CAF were asymptomatic. Twenty
      fistulas originated from the left coronary artery and 9 from the right. The
      pulmonary artery was the most dominant drainage site. Four patients among the
      isolated CAF cases were surgically treated without a cardiopulmonary bypass.
      RESULTS: All patients were discharged from hospital without any perioperative
      complications. Postoperative coronary angiography was done on all patients with
      only one slightly residual CAF flow. The average follow-up time was 9.6 years and
      all patients were asymptomatic and doing well. CONCLUSIONS: Definitive surgical
      correction is safe and effective, with good results. Therefore, it should be
      considered even in asymptomatic patients because of the risk of future
      complications.

PMID- 12220073
TI  - Cerebral protection: the surgeon's view.
AB  - The cardiothoracic team has to be ready with a strategy that corners the
      preoperative to postoperative period, but the cardiothoracic surgeon has to be
      prepared to perform the optimal procedure by concentrating on the procedure and
      avoiding circulatory arrest. If it is not possible to avoid circulatory arrest
      the surgeon should choose the ideal cerebroprotective technique for each patient,
      which is not always the same technique, change the method during the procedure if
      necessary, and remember that cerebral protection is not the same as cerebral
      metabolic preservation.

PMID- 12220074
TI  - Transesophageal echocardiography in the diagnosis of acute aortic syndrome.
AB  - In recent years, technological advances in echocardiography have led to
      improvements in the diagnosis of acute aortic disease. With transesophageal
      echocardiography (TEE) and, particularly, bi- and multiplane probes, the
      physiopathologic understanding of these diseases has widened. Thus, new entities
      such as penetrating ulcer and intramural hematoma have been described and
      differentiated from classical aortic dissection.

PMID- 12220075
TI  - In vivo validation of numerical prediction of blood flow in arterial bypass
      grafts.
AB  - In planning operations for patients with cardiovascular disease, vascular
      surgeons rely on their training, past experiences with patients with similar
      conditions, and diagnostic imaging data. However, variability in patient anatomy
      and physiology makes it difficult to quantitatively predict the surgical outcome
      for a specific patient a priori. We have developed a simulation-based medical
      planning system that utilizes three-dimensional finite-element analysis methods
      and patient-specific anatomic and physiologic information to predict changes in
      blood flow resulting from surgical bypass procedures. In order to apply these
      computational methods, they must be validated against direct experimental
      measurements. In this study, we compared in vivo flow measurements obtained using
      magnetic resonance imaging techniques to calculated flow values predicted using
      our analysis methods in thoraco-thoraco aortic bypass procedures in eight pigs.
      Predicted average flow rates and flow rate waveforms were compared for two
      locations. The predicted and measured waveforms had similar shapes and
      amplitudes, while flow distribution predictions were within 10.6% of the
      experimental data. The average absolute difference in the bypass-to-inlet blood
      flow ratio was 5.4 +/- 2.8%. For the aorta-to-inlet blood flow ratio, the average
      absolute difference was 6.0 +/- 3.3%.

PMID- 12220076
TI  - A layer-specific three-dimensional model for the simulation of balloon
      angioplasty using magnetic resonance imaging and mechanical testing.
AB  - A detailed understanding of the mechanical procedure of balloon angioplasty
      requires three-dimensional (3D) modeling and efficient numerical simulations. We
      have developed a 3D model for eight distinct arterial components associated with
      specific mechanical responses. The 3D geometrical model is based on in vitro
      magnetic resonance imaging of a human stenotic postmortem artery and is
      represented by nonuniform rational B-spline surfaces. Mechanical tests of the
      corresponding vascular tissues provide a fundamental basis for the formulation of
      large strain constitutive laws, which model the typical anisotropic, highly
      nonlinear, and inelastic mechanical characteristics under supraphysiological
      loadings. The 3D finite-element realization considers the balloon-artery
      interaction and accounts for vessel-specific axial in situ prestretches. 3D
      stress states of the investigated artery during balloon expansion and stent
      deployment were analyzed. Furthermore, we studied the changes of the 3D stress
      state due to model simplifications, which are characterized by neglecting axial
      in situ prestretch, assuming plane strain states, and isotropic material
      responses, as commonly utilized in previous works. Since these simplifications
      lead to maximum stress deviations of up to 600%-where even the stress character
      may interchange-the associated models are, in general, inappropriate. The
      proposed approach provides a tool that has the potential (i) to improve
      procedural protocols and the design of interventional instruments on a lesion
      specific basis, and (ii) to determine postangioplasty mechanical environments,
      which may be correlated with restenosis responses.

PMID- 12220077
TI  - Particle image velocimetry assessment of stent design influence on intra
      aneurysmal flow.
AB  - Endovascular stenting appears to be an appealing treatment modality to selected
      complex intracranial aneurysms. However, stents currently used for endovascular
      treatment are not specifically designed for the cerebrovasculature. Stent
      parameters, such as porosity and filament size, have to be carefully optimized
      for long-term successful treatment. We investigated the influence of the stent
      filament size on the intraaneurysmal flow dynamics in a sidewall aneurysm model
      in vitro. Three helical stents with 76% porosity but different filament sizes of
      178, 153, and 127 microm were studied using particle image velocimetry. Twenty
      four pulsatile flow conditions were investigated. The results show that stenting
      significantly reduces intra-aneurysmal vorticity and the mean circulation inside
      the aneurysm is reduced to less than 3% of its value before stenting. For
      constant porosity, a further reduction of the mean circulation, up to 30% can be
      obtained by reducing the filament diameter. For a constant Womersley number, this
      further reduction is accentuated with increase in the peak Reynolds number.
      Further reduction in the mean circulation inside the aneurysm was not achieved
      for the 127 microm stent. With further reduction in filament diameter, the
      helical stent filaments positioned against the aneurysm neck started wavering
      with the flow transferring added momentum into the aneurysm. For stents of
      smaller filament diameter, a supporting ultrastructure is required.

PMID- 12220078
TI  - Theoretical prediction of low-density lipoproteins concentration at the luminal
      surface of an artery with a multiple bend.
AB  - To elucidate the mechanisms of localization of atherosclerotic lesions in man,
      the effects of various physical and hemodynamic factors on transport of
      atherogenic low-density lipoproteins (LDL) from flowing blood to the wall of an
      artery with a multiple bend were studied theoretically by means of a computer
      simulation under the conditions of a steady flow. It was found that due to a
      semipermeable nature of an arterial wall to plasma, flow-dependent concentration
      polarization of LDL occurred at the luminal surface of the vessel, creating a
      region of high LDL concentration distal to the apex of the inner wall of each
      bend where the flow was locally disturbed by the formation of secondary and
      recirculation flows and where wall shear stresses were low. The highest surface
      concentration of LDL occurred distal to the acute second bend where
      atherosclerotic intimal thickening developed. At a Re0=500, the values calculated
      using estimated diffusivities of LDL in whole blood and plasma were respectively
      35.1% and 15.6% higher than that in the bulk flow. The results are consistent
      with our hypothesis that the localization of atherosclerotic lesions results from
      the flow-dependent concentration polarization of LDL which creates locally a
      hypercholesterolemic environment even in normocholesterolemic subjects, thus
      augmenting the uptake of LDL by vascular endothelial cells existing at such
      sites.

PMID- 12220079
TI  - Biphasic poroviscoelastic characteristics of proteoglycan-depleted articular
      cartilage: simulation of degeneration.
AB  - This study investigated the biphasic poroviscoelastic properties of normal and
      proteoglycan-depleted articular cartilage to validate this model for use in the
      diagnosis of degenerated cartilage. A normal control group, a buffer-treated
      control group, and a trypsin-treated proteoglycan-depleted experimental group
      were investigated. Water content and glycosaminoglycan concentration were
      measured for each group in order to assess the affects of buffer treatment and
      trypsin treatment on normal articular cartilage. Histological staining with
      toluidine blue confirmed the depletion of proteoglycan molecules by trypsin
      treatment. Specimens from each group were tested in unconfined compression, and
      the biphasic poroviscoelastic model was fit to the data obtained. No significant
      difference in water content was found between any of the three groups.
      Glycosaminoglycan concentration was found to be significantly lower in the
      trypsin-treated group when compared to both the normal and buffer-treated groups,
      while no difference between normal and buffer-treated specimens was found.
      Specimens from the normal and buffer-treated groups behaved the same
      mechanically. Model parameters from these two groups were not statistically
      different. However, model parameters for the trypsin-treated group were
      statistically different from those from the other two groups, suggesting that the
      biphasic poroviscoelastic model may be a powerful diagnostic tool for
      degenerative articular cartilage.

PMID- 12220080
TI  - Prediction of hip fracture can be significantly improved by a single biomedical
      indicator.
AB  - Femoral neck fractures are a relevant clinical and social problem. The aim of
      this study was to improve the prediction of patients at-risk of femoral neck
      fracture with respect to the current densitometric-based methods. In particular,
      finite element models were used to assess the prediction accuracy obtained by
      combining together data from the bone density distribution, the proximal femur
      anatomy, and the fall-related loading conditions. Two-dimensional finite element
      models were developed based on dual energy x-ray absorptiometry data. A
      population of 93 elder Caucasian women (half of them reporting a femoral neck
      fracture) were retrospectively classified both using the standard clinical
      protocol and Bayes' linear classifiers. This study showed that the bone mineral
      density in the femoral neck region dominated the fracture event (65% accuracy).
      Adding the subject's height and the neck-shaft angle to the bone density
      increased the accuracy to 77%. The classification accuracy was further improved
      to 82% by including the peak principal tensile strain obtained from the finite
      element analyses. This research demonstrated that adding one single biomechanical
      indicator to the standard clinical measurements improves the identification of
      patients at-risk of femoral neck fracture.

PMID- 12220081
TI  - A computational model for glycogenolysis in skeletal muscle.
AB  - A dynamic model of the glycogenolytic pathway to lactate in skeletal muscle was
      constructed with mammalian kinetic parameters obtained from the literature.
      Energetic buffers relevant to muscle were included. The model design features
      stoichiometric constraints, mass balance, and fully reversible thermodynamics as
      defined by the Haldane relation. We employed a novel method of validating the
      thermodynamics of the model by allowing the closed system to come to equilibrium;
      the combined mass action ratio of the pathway equaled the product of the
      individual enzymes' equilibrium constants. Adding features physiologically
      relevant to muscle-a fixed glycogen concentration, efflux of lactate, and
      coupling to an ATPase--alowed for a steady-state flux far from equilibrium. The
      main result of our analysis is that coupling of the glycogenolytic network to the
      ATPase transformed the entire complex into an ATPase driven system. This steady
      state system was most sensitive to the external ATPase activity and not to
      internal pathway mechanisms. The control distribution among the internal pathway
      enzymes-although small compared to control by ATPase-depended on the flux level
      and fraction of glycogen phosphorylase a. This model of muscle glycogenolysis
      thus has unique features compared to models developed for other cell types.

PMID- 12220082
TI  - Antibody penetration into a spherical prevascular tumor nodule embedded in normal
      tissue.
AB  - A finite-element (FE) method is used to numerically solve a pharmacokinetic model
      that describes the uptake of systemically administered antibody (mAb) in a
      prevascular spherical tumor nodule embedded in normal tissue. The model
      incorporates plasma kinetics, transcapillary transport, lymphatic clearance,
      interstitial diffusion in both the normal tissue and tumor, and binding
      reactions. We use results from the FE analysis to assess previous predictions
      that employed either a Dirichlet boundary condition (b.c.), or an approximate,
      composite (Dirichlet and Neumann) b.c. at the tumor surface. We find that the
      Dirichlet b.c. significantly overpredicted the mean total tumor mAb
      concentration. In contrast, the composite b.c. yielded good agreement with FE
      predictions, except at early times. We also used the FE model to investigate the
      influence of the approximately 30-fold difference in the values of mAb diffusion
      coefficient measured by Clauss and Jain (Cancer Res. 50:3487-3492, 1990) and Berk
      et al. (Proc. Natl. Acad. Sci. U.S.A. 94:1785-1790, 1997). For low diffusivity,
      diffusional resistance slows both mAb uptake by and efflux from the tumor. For
      high diffusivity at the same mAb dose, more rapid uptake produces earlier and
      higher peak mAb levels in the tumor, while the efflux rate is limited by the
      dissociation of the mAb-tumor antigen complex. The differences in spatial and
      temporal variation in mAb concentration between low and high diffusivities are of
      sufficient magnitude to be experimentally observable, particularly at short times
      after antibody administration.

PMID- 12220083
TI  - Homotypic interactions of soluble and immobilized osteopontin.
AB  - Osteopontin (OPN) is an extracellular matrix protein found in bones and teeth,
      where it accumulates at matrix-matrix interfaces. We postulate that OPN interacts
      homotypically and heterotypically in the adhesion of apposing matrices. Using
      suspensions of OPN-coupled aldehyde/sulfate latex spheres, we measured the
      strength of homotypic OPN-OPN binding in vitro. Doublets formed through shear
      induced collisions in a cone and plate rheoscope were subjected to shear stresses
      >0.6 Nm(-2) and the fraction broken up determined over 60 s. Rapid initial
      breakup of 35% of doublets was followed by very slow breakup of the remaining
      65%. Monte Carlo simulation of the breakup kinetics pointed to the existence of
      low and high bond strength populations of doublets. Dynamic light scattering
      spectroscopy of soluble OPN showed that 27% by mass existed as dimers. We
      postulate that OPN dimers binding to monomers account for the low strength bonds
      since a strong bond has already formed between the molecules of the dimer. In
      contrast, OPN-OPN monomer bonds had higher tensile strength than bonds between
      the high-affinity interaction of IgG and protein G, previously studied. Antibody
      blocking studies showed that the self-binding region of OPN resides in the C
      terminus. These data suggest that homotypic OPN-OPN bonds have physiologically
      significant strength, supporting the hypothesis that OPN-OPN binding and self
      assembly participate in adhesion within mineralized tissues.

PMID- 12220085
TI  - Primary health care in the era of HIV/AIDS. some implications for health systems
      reform.
AB  - In this article it is argued that the current emphasis on third generation
      reforms to health systems places at risk the empowering comprehensive agenda of
      second generation reforms. Using the HIV/AIDS epidemic in South Africa as an
      exemplar, the authors demonstrate the importance of retaining this agenda. They
      suggest that the emphasis on 'packaged' priority programmes with measurable
      outcomes, which characterizes third generation reforms, needs to be accompanied
      by the reorientation of primary health care providers towards an empowering
      comprehensive approach to care. In addition, using psychodynamic principles, they
      also show how certain aspects of the health care system need restructuring to
      provide containment and support for such care.

PMID- 12220084
TI  - Cell migration on cell-internalizable ligand microdepots: a phenomenological
      model.
AB  - We have shown that collagen "ligand associated microdepots" (LAMs) at polymer
      substrates can significantly enhance levels of skin epidermal cell migration
      (Tjia and Moghe, Tissue Eng. 8:247-259, 2002). In this study, we have further
      examined the dynamics of cell-LAM interactions, primarily through a
      phenomenological model to examine the differential effects of LAM-cell binding
      and LAM internalization within the cells. Based on the experimental data of cell
      migration and LAM dynamics under selected conditions, the model was solved to
      yield rates of LAM binding and internalization at various LAM substrate
      densities. The clearance dynamics of LAMs computed at various times from the
      model matched well with the LAM clearance kinetics observed experimentally. The
      model was used to generate simulations of the rates of LAM binding and
      internalization over time, under conditions of differential exogenous activation.
      Our model analysis suggests that the rate of cell migration can be sensitively
      governed by rate of cellular sampling of LAMs, given by differential rates of LAM
      binding and internalization. Maximal cell migration was found to occur during LAM
      presentation regimes (LAM spatial density) that engendered concerted changes in
      the extent of cell activation, as measured via net tyrosine kinase activity, due
      to LAM sampling dynamics.

PMID- 12220086
TI  - The spatial epidemiology of cholera in an endemic area of Bangladesh.
AB  - This paper defines high-risk areas of cholera based on environmental risk factors
      of the disease in an endemic area of Bangladesh. The risk factors include
      proximity to surface water, high population density, and low educational status,
      which were identified in an earlier study by the authors. Cholera data were
      analyzed by spatially referenced extended household units for two time periods,
      1983-1987 and 1992-1996. These periods were chosen because they had different
      dominant cholera agents. From 1983-1987 classical cholera was dominant and from
      1992-1996 El Tor was dominant. By defining high-risk areas based on risk factors,
      this study builds a spatial risk model for cholera. The model is then evaluated
      based on the locations of observed cholera cases. The study also identifies the
      determinants of death due to cholera for the two different time periods dominated
      by the different cholera agents. The modeled risk areas that were based on the
      risk factors were found to correspond with actual distributions of cholera
      morbidity and mortality. The high-risk areas of the dominant cholera agents are
      relatively stable over time. However, from 1983-1987 El Tor cholera, which was
      not the dominant agent during that period, was not associated with high-risk
      areas, suggesting that the El Tor habitat may have changed over time. The case
      fatality rate for cholera was related to proximity to a diarrhea treatment
      hospital in the study area.

PMID- 12220087
TI  - An investigation of the health beliefs and motivations of complementary medicine
      clients.
AB  - The current study was concerned with factors associated with the use of
      complementary medicine (CM). The reasons for CM use were examined by dividing
      complementary medicine clients into two groups based on the frequency and length
      of their use of complementary therapies, and comparing them with conventional
      medicine clients as well as to each other. New/infrequent CM clients (n = 70),
      established CM clients (n = 71), and orthodox medicine clients (n = 58) were
      distinguished on the basis of health beliefs, socio-demographic, medical, and
      personality variables. Different patterns of predictors of CM use emerged
      depending on which client groups were compared. In general, health-aware
      behaviors and dissatisfaction with conventional medicine were the best predictors
      of overall and initial/ infrequent CM use, and more frequent health-aware
      behaviors were associated with continued CM use. Medical need also influenced the
      choice to use CM, and was the best predictor of committed CM use, with the
      established CM clients reporting more health problems than the new/infrequent CM
      group. Overall, income was a significant discriminator, but did not predict
      initial or continued CM use. Openness to new experience was associated with CM
      use in general, but was most notable in the decision to initially try or explore
      using CM. The findings support the utility of the three components (predisposing,
      enabling, and need factors) of the socio-behavioral model for explaining why some
      people choose CM. Overall, the results of the current study suggest that CM
      clients need to be looked at in more sophisticated ways, rather than being
      treated simply as a homogenous group with similar beliefs, motivations and needs.

PMID- 12220088
TI  - Gender and health in rural China: evidence from Hebei Province.
AB  - Gender differences in health and health behavior are well established in Western
      societies, but little is known about gender health inequalities in rural China.
      We examine patterns of age-sex differences in health and health behavior of men
      and women in rural HeBei, People's Republic of China, and consider the extent to
      which these patterns resemble gender health inequalities observed in North
      America and Western Europe. The data analyzed were collected from 14,895
      individuals residing in 288 villages in the HeBei Province. The results show that
      gender differences emerged at a later age than generally reported in Western
      societies. Poorer health among women, as compared with men, becomes observable
      during young adulthood (25-44) rather than at adolescence, and reached its peak
      among older adults (45-59) rather than during the productive and reproductive
      stage of the life course. Among the elderly, the differences between the health
      and the health behavior of men and women narrowed, similar to many reports in
      North America and Western Europe. Most importantly, no gender differences in
      mental health were observed. These findings suggest that the older adult age
      group (45-59) may be appropriate for interdisciplinary efforts to advance the
      understanding regarding the relative contributions of nature and nurture to
      gender differences in health.

PMID- 12220089
TI  - Gradients in risk for youth injury associated with multiple-risk behaviours: a
      study of 11,329 Canadian adolescents.
AB  - This study used the Canadian version of the World Health Organization-Health
      Behaviour in School-Aged Children (WHO-HBSC) Survey to examine the role of
      multiple risk behaviours and other social factors in the etiology of medically
      attended youth injury. 11,329 Canadians aged 11-15 years completed the 1997-1998
      WHO-HBSC, of which 4152 (36.7%) reported at least one medically attended injury.
      Multiple logistic regression analyses failed to identify an expected association
      between lower socio-economic status and risk for injury. Strong gradients in risk
      for injury were observed according to the numbers of multiple risk behaviours
      reported. Youth reporting the largest number (7) of risk behaviours experienced
      injury rates that were 4.11 times (95% CI: 3.04-5.55) higher than those reporting
      no high risk behaviours (adjusted odds ratios for 0-7 reported behaviours: 1.00,
      1.13, 1.49, 1.79, 2.28, 2.54, 2.62, 4.11; p(trend) < 0.001). Similar gradients in
      risk were observed within subgroups of young people defined by grade, sex, and
      socio-economic level, and within restricted analyses of various injury types
      (recreational, sports, home, school injuries). The gradients were especially
      pronounced for severe injury types and among those reporting multiple injuries.
      The analyses suggest that multiple risk behaviours may play an important role in
      the social etiology of youth injury, but these same analyses provide little
      evidence for a socio-economic risk gradient. The findings in turn have
      implications for preventive interventions.

PMID- 12220090
TI  - Predictors of Canadian legislators' support for tobacco control policies.
AB  - It is clear that regulatory strategies can be effective in reducing tobacco use.
      Because legislators ultimately determine whether many of these policies are
      enacted, they are a key focus for tobacco policy research. This study identifies
      political and personal predictors of Canadian legislators' support for tobacco
      control policies. Data are from a 1996-97 survey of federal, provincial and
      territorial legislators. Multivariate regression analysis was used to assess
      relationships between five groups of variables (political factors including
      political ideology, personal characteristics, tobacco experiences, tobacco
      knowledge, interest group saliency) and support for tobacco control based on an
      11-item scale. Support for tobacco control varied by political party. Support was
      higher among legislators who thought government had a duty to promote healthy
      lifestyles, knew second-hand smoke could cause lung cancer, knew tobacco caused
      more deaths than alcohol, and said they wanted more contact with medical
      associations about tobacco issues. Support was lower among current smokers and
      those with tobacco industry jobs in their ridings. The findings indicate that
      political party membership cannot be ignored in enlisting legislator support for
      tobacco control. It also appears that legislators who oppose tobacco control
      measures may not be opposed to tobacco control per se, but are more generally
      opposed to a government role in health promotion. Thus, public health
      professionals and tobacco control advocates need to be more attentive to the way
      tobacco control issues are framed for particular legislators. Further, meetings
      with health groups about tobacco issues would be welcomed by many legislators;
      non-governmental organizations and other health advocates could work to increase
      tobacco knowledge among legislators.

PMID- 12220091
TI  - Encountering the downward phase: biographical work in people with multiple
      sclerosis living at home.
AB  - This qualitative study examines how individuals in an advanced stage of multiple
      sclerosis (MS) who live at home, accommodate to their illness. The downward phase
      in the illness trajectory of MS often consists of a lengthy period of gradual
      decline. According to Corbin and Strauss's framework, accommodation is
      conceptualized as biographical work that refers to the actions taken to retain
      control over the life course and to give life meaning again. For our purpose semi
      structured interviews with 22 people with MS were conducted and compared with 21
      interviews with their family caregivers. The analysis consisted of fragmenting
      and connecting the data and involved close reading and constant comparison. The
      continuity of biography is at risk since body and performance failures lead to
      the loss of salient aspects of self. Participants interpret MS as an all
      encompassing illness and emphasize the process of having to give up everything.
      Four case stories are described to demonstrate the complex intertwining of the
      biographical processes and to show the range in biographical accommodation. Some
      patients are capable of putting their lives back together again, while others
      retreat or do not consider MS a part of their lives. The unpredictable course of
      MS makes it impossible to give new direction to the life course.

PMID- 12220092
TI  - Cost characteristics of hospitals.
AB  - Modern hospitals are complex multi-product organisations. The analysis of a
      hospital's production and/or cost structure should therefore use the appropriate
      techniques. Flexible functional forms based on the neo-classical theory of the
      firm seem to be most suitable. Using neo-classical cost functions implicitly
      assumes minimisation of (variable) costs given that input prices and outputs are
      exogenous. Local and global properties of flexible functional forms and short-run
      versus long-run equilibrium are further issues that require thorough
      investigation. In order to put the results based on econometric estimations of
      cost functions in the right perspective, it is important to keep these
      considerations in mind when using flexible functional forms. The more recent
      studies seem to agree that hospitals generally do not operate in their long-run
      equilibrium (they tend to over-invest in capital (capacity and equipment)) and
      that it is therefore appropriate to estimate a short-run variable cost function.
      However, few studies explicitly take into account the implicit assumptions and
      restrictions embedded in the models they use. An alternative method to explain
      differences in costs uses management accounting techniques to identify the cost
      drivers of overhead costs. Related issues such as cost-shifting and cost
      adjusting behaviour of hospitals and the influence of market structure on
      competition, prices and costs are also discussed shortly.

PMID- 12220093
TI  - Ready to die: a postmodern interpretation of the increase of African-American
      adolescent male suicide.
AB  - African-Americans have typically registered lower rates of suicide than other
      ethnic groups. In the last 20 years this pattern has changed, particularly among
      young African-Americans between the ages of 15 and 19 (National Center for Injury
      Prevention and Control, Mortality Statistics, 1998, Atlanta, GA). Today, young
      African-American males are as likely to commit suicide as their White
      counterparts. To date, the research conducted regarding this phenomenon has been
      inconclusive and existing suicide interventions appear to have no effect on
      reducing this behavior among young African-Americans. This paper synthesizes
      classical (Durkheim, Suicide, 1979, Free Press, New York) and postmodern (Beck,
      Risk Society: Towards a New Modernity, 1992, Sage, London; Bauman, Modernity and
      Ambivalence, Cornell University Press, Ithaca, 1991) social theories in order to
      provide a more complete theoretical explanation for the increase in the suicide
      rate among adolescent African-American males. Postmodern society is typified by:
      (1) institutional deconstruction; (2) decreased collectivism; (3) increased
      normlessness and helplessness; and (4) exacerbated personal risk for stress. It
      is therefore possible to hypothesize that postmodernity characteristically
      loosens the bonds between the individual and society, thereby increasing
      vulnerability to depression, related pathologies (such as substance abuse), and
      suicide. African-Americans tend to be more affected/vulnerable because they are
      concentrated in resource-poor, low income areas, and institutions that provided
      social support (family, religious, community) and protected individuals from
      societal risk factors, have gradually been dissolving in postmodern societies. We
      argue that young African-American males of today are more exposed to stressors
      which increase psychological distress thus increasing depression and related
      pathological behaviors such as suicide. The main reason behind this increase is
      found in the inability of institutions to offer protection from psychological
      distress. Overall, this paper presents a postmodern, macro-level framework to
      explain the increase in suicide among African-American male adolescents.

PMID- 12220094
TI  - State-event relations among indicators of susceptibility to mental distress in
      Wythenshawe in the UK.
AB  - This paper explores the utility of concepts drawn from psychosocial theory as
      predictors of the proneness to mental distress among the residential population
      of a large suburban council estate (Wythenshawe, South Manchester). In this
      respect, items are selected and tested to form composite variables measuring
      individual ratings with regard to notions of structural risk, personal
      vulnerability, goal-setting behaviour, quality of life, and the frequency of life
      events and restricted opportunities. Mental distress is enumerated on the
      standard GHQ12-point scale. The design makes the distinction between composite
      variables that record persistent states and those which count events and
      aspirations immediate to the individual's present experience. To examine the
      consequences of this difference between indicators of prevalence and incidence,
      our analysis adopts a two-stage multiple regression format. The first examines
      these state-event interactions among the composite variables, while the second
      tests the separate significance of these types as predictors of GHQ12. The
      findings reveal significant proportions of the variation in GHQ12 are be
      explained either by associations with the ageing process or by those linked to
      subjective indicators of the quality of life. In contrast, structural deprivation
      correlates less significantly with the reporting of psychiatric distress in this
      socially homogeneous population. The discussion considers the methodological
      implications of these relationships for understanding common mental health
      problems together with their connotations for health policy.

PMID- 12220095
TI  - Early origins and adult correlates of psychosomatic distress.
AB  - Previous studies have demonstrated associations between fetal insults and
      psychological and developmental outcomes in children and adolescents. It is not
      clear whether psychosomatic problems in adults also have early origins. This
      study involved full-term live-born singletons free of congenital anomaly in the
      1970 British Birth Cohort Study. Birthweight, gestational age, maternal smoking,
      parental social class and birth order were recorded around the time of birth.
      Psychological and somatic distresses were measured by the Malaise Inventory at
      age 26. A number of socio-behavioural covariates were also measured at this time.
      Multiple (least square) regression analysis showed that birthweight standardised
      for gestational age had a "reverse J" relation with psychological distress (p <
      0.05); gestational age was inversely related to psychological distress (each p <
      0.05); levels of maternal smoking were positively related to both psychological
      distress and somatic distress (each p < 0.01). Logistic regression analyses of
      high levels of psychological distress and somatic distress gave similar results.
      The findings were not strongly affected by adjustment for various adult
      correlates. In supplementary analyses multiple imputation was used to handle loss
      to follow-up and missing values at age 26. Approximately, the same patterns of
      associations were found. The results support the hypothesis of a biological link
      between perinatal factors and psychological distress in adults. The strengths of
      the associations were compared with those between the outcome and adult
      correlates.

PMID- 12220096
TI  - Social status determinants of control in individuals' accounts of their mental
      illness.
AB  - We examine the determinants of patients' accounts of their own mental illness. In
      particular, we examine the factors that affect the likelihood of attributing
      one's own mental illness to controllable factors rather than non-controllable
      factors. Our quantitative measure of attributional control is derived from the
      coding of in-depth interviews with people with severe mental illness seeking
      treatment for the first time (N = 144). We find that those who occupy positions
      of social disadvantage (particularly African-American males and those who receive
      public assistance) are less likely to attribute their illness to controllable
      sources, suggesting that personal mental illness attributions are systematically
      related to a person's social location. We outline the significance of these
      findings for research on the psychological consequences of mental illness
      attributions.

PMID- 12220097
TI  - Marginal employment and health in Britain and Germany: does unstable employment
      predict health?
AB  - This study examines the possible health impact of marginal employment, including
      both temporary and part-time employment schemes. It addresses three research
      questions: (1) Are employed people with a fixed-term contract or no contract more
      likely to report poor health than those who hold jobs with permanent contracts?
      (2) Are part-time employed respondents (even when they hold jobs with permanent
      contracts) more likely to report poor health than full-time workers? (3) Does
      change in employment stability (i.e., from employment with permanent contract to
      fixed-term or no contract employment and vice-versa) have an impact on health
      status? Logistic regression models were used to analyze panel data from Britain
      and Germany (1991-1993), available in the Household Panel Comparability Project
      data base. We included 10,104 respondents from Germany and 7988 from Britain. A
      single measure of perceived health status was used as the dependent variable.
      Controlling for background characteristics, the health status of part-time
      workers with permanent contracts is not significantly different from those who
      are employed full-time. In contrast, fulltime employed people with fixed-term
      contracts in Germany are about 42 per cent more likely to report poor health than
      those who have permanent work contracts. In Britain, only part-time work with no
      contract is associated with poor health, but the difference is not statistically
      significant. We conclude that monitoring the possible health effects of the
      increasing number of marginal employment arrangements should be given priority on
      the social welfare research agenda.

PMID- 12220098
TI  - The effects of introducing prospective payments to general hospitals on length of
      stay, quality of care, and hospitals' income: the early experience of Israel.
AB  - A new reimbursement system for general hospitals in Israel was introduced in July
      1990. The new system specified that for 15 selected procedures, hospitals would
      be paid by the insurers prospectively, rather than by the traditional per-diem
      arrangement. The rates were determined by the Ministry of Health. Henceforth, the
      number of selected procedures has increased and by now 40 procedures are
      included. In line with the ever-lasting interest in the effect of financial
      incentives on suppliers of medical care, the purpose of this paper is to examine
      the first-year effect of this change on the volume of activity, length of stay,
      quality of care, and hospitals' real income. We focused on five selected
      procedures (cholecystectomy, hysterectomy, hip replacement, operations on lens
      and heart surgeries) performed in the four largest Israeli medical centers
      (Sheba, Sorasky, Rambam, and Hadassah). The analysis includes more than 17,000
      hospitalizations occurring during two years prior to the change (July 1988-June
      1990) and the first year after its implementation (July 1990-June 1991). We,
      therefore, examined, the short-term effects, wherein changes in the hospitals'
      behavior are reflected mainly in the above-mentioned hospitalization
      characteristics. Further analysis will be required to examine the long-run
      implications of the change as well as its effect on the rest of the general
      inpatient sector in Israel.

PMID- 12220099
TI  - Interdisciplinary collaboration within Quebec Community Health Care Centres.
AB  - Central to the success of many recent health system reforms is the implementation
      of new primary health care delivery models. The central characteristic common to
      these new models usually emphasises interdisciplinary collaboration. Using
      empirical research, this paper studies interdisciplinary collaboration among
      various groups of professionals within an original Canadian primary health care
      delivery model, the Quebec Community Health Care Centres (CCHCs). The entire
      population of more than 150 CHCCs have been surveyed. The goals of this study are
      (1) to measure the achieved intensity of inter-professional collaboration among
      Quebec CHCCs, and (2) to identify the organisational and professional factors
      fostering or limiting interdisciplinary collaboration. The results show that
      Quebec CHCCs have reached modest results in achieving interdisciplinary
      collaboration especially since interdisciplinary collaboration is a central
      objective that has been pursued for more than 25 years. This study demonstrates
      that the main factors associated with interdisciplinary collaboration are closely
      linked to work group internal dynamics. Interdisciplinary collaboration is linked
      to the simultaneous and antagonistic effect of some central intragroup process
      factors. Conflicting values and beliefs are present that both enhance and limit
      interdisciplinary collaboration. The presence of conflicting stimuli seriously
      undermines the strength of the CHCC work group's shared beliefs and strongly
      limits interdisciplinary collaboration. The results also stress the importance of
      administrative formalisation initiatives to enhance collaboration among different
      professions. The efficacy of formalisation in this context is based on its
      capacity to offer an articulated and operative interdisciplinary framework that
      can generate a counteractive effect to the traditional professional framework. It
      offers concrete rules that help align the work group beliefs with
      interdisciplinary values. The formalisation of functions and processes appears
      thus to be an interesting means to further interdisciplinary collaboration.

PMID- 12220100
TI  - Reflections on the management of reproductive failure in the antiphospholipid
      syndrome--the clinician's perspective.
AB  - It is well known that women with systemic lupus erythematosus (SLE) who have
      antiphospholipid antibodies (aPL) are at increased risk for pregnancy loss.
      Additionally, other reproductive processes, such as unexplained infertility and
      implantation failure after in vitro fertilization and embryo transfer may be
      affected by aPL. Thus, clinical manifestations of the so-called 'gynaeco
      obstetrical antiphospholipid syndrome' have been expanded into the concept of the
      'reproductive autoimmune failure syndrome'. However, this is still a matter of
      debate with no general agreement with respect to both pathophysiological
      significance of the presence of aPL and patient management. This article analyses
      a number of controversies in the management of reproductive failure potentially
      associated with aPL in order to help clinicians dealing with such condition in
      daily clinical practice.

PMID- 12220101
TI  - Development and assessment of a World Wide Web site for systemic lupus
      erythematosus patient information.
AB  - Patient education is an important component of the management of chronic diseases
      such as SLE. We have investigated the value of the World Wide Web as a medium for
      delivery of SLE patient information. Volunteers recruited from the clinic and
      from the website completed interviews and questionnaires aimed at defining their
      information needs. A new website was then established and its impact on users
      tested using knowledge questionnaires. The new website was used extensively (20
      30 users each day) over the 24 month period of study until April 2001. A total of
      510 participants completed an online questionnaire that showed that for some
      users it was their first use of the internet to gather lupus information, but the
      majority (58.9%) accessed it at least monthly for this purpose. We also found
      that, while most users (56.9%) found current disease information was at an
      appropriate level, 37.5% thought it was too basic. Knowledge questionnaires from
      42 participants before and after using the site showed a significant rise in
      users' knowledge of the areas covered by the site. As far as we are aware this
      study is the first to show that a patient-oriented website can have a positive
      effect on disease knowledge. The relative ease with which good quality
      information can be disseminated via the web suggests that this medium is likely
      to be less costly and perhaps more educationally effective than printed
      information, and so is likely to become a primary vehicle for patient education.
      The website tested can be found at: www.rheumatology.bham.ac.uk/lupus/intro.html.

PMID- 12220102
TI  - Prediction of lupus nephritis in patients with systemic lupus erythematosus using
      artificial neural networks.
AB  - Artificial neural networks are intelligent systems that have been successfully
      used for prediction in different medical fields. In this study, efficiency of
      neural networks for prediction of lupus nephritis in patients with systemic lupus
      erythematosus (SLE) was compared with a logistic regression model and clinicians'
      diagnosis. Overall accuracy, sensitivity and specificity of the optimal neural
      network were 68.69, 73.77 and 62.96%, respectively. Overall accuracy of neural
      network was greater than the other two methods (P-value < 0.05). The neural
      network was more specific in predicting lupus nephritis (P-value < 0.01), but
      there was no significant difference between sensitivities of the three methods.
      Sensitivities of all three methods were greater than their specificities. We
      concluded that neural networks are efficient in predicting lupus nephritis in SLE
      patients.

PMID- 12220103
TI  - Characterization of CD3+ CD4- CD8- (double negative) T cells in patients with
      systemic lupus erythematosus: activation markers.
AB  - Systemic lupus erythematosus (SLE) is characterized by B cell hyperactivity and
      the production of autoantibodies, some of which (antibodies to dsDNA) are thought
      to be pathogenic. T helper cells drive the production of autoantibodies and the
      aim of this study is to characterize phenotypically a subpopulation of T cells
      (the CD3+ CD4- CD8-, double negative (DN) T cells) previously identified as
      helping to enhance anti-DNA antibodies in patients with SLE. Data were obtained
      using FACS staining of DN T cells that had been purified from PBMCs by magnetic
      bead separation. The percentage of TCR alphabeta+ DN T cells was found to be
      significantly higher in patients with SLE as compared with controls (P = 0.02),
      although there was no significant increase in total percentage of DN T cells,
      which includes TCR gammadelta+ cells. Activation markers HLA-DR and CD69, the
      costimulatory molecule CD28 and CTLA-4 were all expressed on the surface of a
      higher percentage of DN T cells in patients with SLE than in patients with
      rheumatoid arthritis (RA) or healthy controls (HC). More DN T cells from patients
      with SLE were of CD45RA phenotype than was found in controls, while CD45RO
      expressing cells were reduced. In addition, DN T cells from patients with SLE
      expressed significantly higher levels of HLA-DR (P = 0.006), CD28 (P = 0.05),
      CTLA4 (P = 0.03) and CD45RA (P = 0.05) on the cell surface than those from the
      CD4/8 population. Correlation of expression of the markers measured with various
      parameters of disease activity and severity showed that high levels of HLA-DR
      expression correlated with high circulating serum C3 (> 0.9 IU/ml), indicating
      that an activated phenotype is consistent with severe disease.

PMID- 12220104
TI  - Characterization of CD3+ CD4- CD8- (double negative) T cells in patients with
      systemic lupus erythematosus: production of IL-4.
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic disease that
      may affect every organ or system in the body. We have shown previously that the
      TCR alphabeta+ subpopulation of CD3+ CD4- CD8-, DN T cells is expanded in
      patients with SLE and that double negative T cells express increased levels of
      activation markers compared both with healthy people and with patients with
      rheumatoid arthritis, (RA) as autoimmune controls. The aim of this study was to
      characterize these cells in terms of their ability to produce IL4, a Th2
      cytokine, both spontaneously and after mitogen stimulation. It was found that a
      higher percentage of TCR alphabeta+ double negative T cells from patients with
      SLE contained IL4 constitutively than did the same population of cells from
      healthy people or from those with RA. After mitogen stimulation, there was no
      significant difference in the amount of IL4 produced by each of the three groups.
      Further study of patients producing high levels of IL4 (about one third of the
      patients) indicated that they had a lower percentage of alphabeta+ T cells in the
      double negative compartment than did patients with fewer IL4 containing cells.

PMID- 12220105
TI  - Low-dose pulse methylprednisolone for systemic lupus erythematosus flares is
      efficacious and has a decreased risk of infectious complications.
AB  - We sought to test our clinical impression that using a low dose
      methylprednisolone pulse (MEP; < or = 1500 mg over 3 days) in treating flares of
      systemic lupus erythematosus (SLE) was effective and associated with fewer
      serious infections. We retrospectively studied SLE patients who received MEP
      between 1989 and 2000. A 'low dose' group of 26 patients who had received 1-1.5 g
      and a 'high dose' group of 29 patients who received 3-5 g of MEP were identified.
      SLEDAI scores and prednisolone doses were recorded at the time of MEP pulses and
      6 months later. All serious infections (requiring admission and i.v. antibiotics)
      occurring during this 6 month period and their outcomes were recorded. Both
      groups had similar demographic data, initial SLEDAI scores, i.v. cyclophosphamide
      use, and SLE organ involvement. Despite high- and low-dose MEP being efficacious
      in controlling disease activity (lowering of SLEDAI scores and subsequent
      prednisolone dose) there were only nine episodes of serious infection in seven
      patients in the low-dose group compared with 20 episodes in 17 patients from the
      high-dose group (P = 0.04). In both groups a majority of infections (75 and 77%
      in the high- and low-dose groups) occurred in the first month after MEP. Those
      with a low serum albumin (< 20 g/l) had an increased risk of mortality (OR 44,
      90% CI 6.19-312.98) and a trend towards greater numbers of infections. Low-dose
      MEP was effective in controlling SLE flares and associated with fewer serious
      infections than traditional high-dose MEP.

PMID- 12220106
TI  - Histopathology of lupus-like nephritis in Dnase1-deficient mice in comparison to
      NZB/W F1 mice.
AB  - Deoxyribonuclease 1 (Dnase1)-deficient mice develop symptoms of Systemic lupus
      erythematosus (SLE). Here we analysed the renal histopathology of these animals
      in comparison to F1 hybrids of New Zealand black and white mice (NZB/W F1), an
      established model of SLE. Animals were divided into three groups according to the
      presence of anti-nuclear antibodies (ANA) and renal lesions. Groups 1a-1c were
      healthy, whereas group 2 and 3 were classified as lupus-prone and affected.
      Subendothelial and/or mesangial immune complex deposits, mesangial and
      endocapillary proliferation, haematoxylin bodies and platelet aggregation were
      detected in both mouse strains but were more severe in the NZB/W F1 mice. The
      lupus nephritis was classified as a proliferating (WHO type III or IV), which
      appeared to be preceded by a mesangial form (WHO type II). Subclassification of
      the ANA revealed a high prevalence of anti-nucleosome antibodies in Dnase1
      deficient mice, whereas NZB/W F1 mice developed autoantibodies against a broad
      range of chromatin constituents. Mapping of the murine Dnase1 gene locus to
      chromosome 16A1-3 did not coincide with one of the reported susceptibility loci
      in the NZB/W F1 model, although a reduced Dnasel serum and urine activity has
      been described previously in these mice.

PMID- 12220107
TI  - Estimating the incidence of systemic lupus erythematosus in a tropical region
      (Natal, Brazil).
AB  - The objective of the study was to evaluate the incidence of Systemic Lupus
      Erythematosus (SLE) in a tropical urban community (Natal city, Brazil). Only
      patients living in Natal, a city in the northeastern area of Brazil, older than
      15 years, and who fulfilled at least four of the American College of Rheumatology
      criteria between 1 January 2000 and 31 December 2000, were included. Four sources
      were used to identify new cases of SLE: (1) the University Hospital; (2) 'health
      units' and hospitals of the public health network; (3) specialists at private
      hospitals and outpatient clinics; and (4) three laboratories performing
      antinuclear antibody (ANA) determination. Census data from 2000 for Brazilian
      population was used to calculate incidence rate. The standardized mortality ratio
      (SMR) method and 95% confidence intervals (95% CI) were calculated. Forty-three
      patients were diagnosed as new SLE cases in 2000. The calculated incidence was
      8.7/100,000/year (95% CI 6.3-11.7). Thirty-eight patients were female
      14.1/100,000/year (95% CI 10.0-19.3) and five were male 2.2/100,000/year (95% CI
      0.7-5.2). The mean age of new SLE cases was 31.8 years old. (95% CI 27.8-35.8).
      The mean age for females was 31.4 and for males was 35.0 years old. The median of
      disease duration (time between onset of the first ACR criterion for SLE and
      diagnosis) was 10 months (1-72 months). This study demonstrated a high incidence
      of SLE in Natal, apparently higher than reported in other places. The mean age at
      diagnosis seems lower than referred by other studies. The observed differences
      may be due to ethnic and/or environmental factors.

PMID- 12220108
TI  - Rapidly progressive lupus glomerulonephritis and concomitant microangiopathy in
      an adolescent.
AB  - We describe our experience managing a 16-year-old girl with systemic lupus
      erythematosus (SLE) who presented concomitantly with rapidly progressive
      glomerulonephritis (RPGN) and a thrombotic microangiopathic hemolytic anemia
      (TMAHA). Her renal biopsy showed evidence of diffuse proliferative
      glomerulonephritis without glomerular microthrombi. The patient was treated with
      a combination of intravenous corticosteroids and cyclophosphamide, as well as
      plasmapheresis, with an excellent response resulting in complete disease
      remission. The purpose of our report is to make health professionals more aware
      of TMAHA as a complication of SLE, since the occurrence of TMAHA may confuse the
      clinical picture, and since its treatment with plasmapheresis is life saving, if
      performed early.

PMID- 12220109
TI  - Atmospheric NO2 and CO concentration in Lima, Peru.
AB  - The atmospheric concentration of NO2 in Lima, Peru was measured through 1 year
      using passive samplers. The concentration was stable and evident seasonal change
      was not observed. Also, the distribution of NO2 concentration in entire Lima was
      monitored twice in different seasons. The average NO2 concentrations at 33 and 27
      sites of these monitoring were 17.1 and 15.3 ppb, respectively. NO2 distribution
      was high in the downtown area and decreased gradually with distance from there.
      The wind that almost always blew from the ocean had a great influence on it. High
      NO2 level and the change of CO concentration suggest that the residential area in
      the northeast side forms a topological channel among hills to blow out the
      pollutants from the downtown area.

PMID- 12220110
TI  - Arsenic contamination of the environment: a new perspective from central-east
      India.
AB  - This paper reports a regional contamination of the environment in central-east
      India that does not share geology or boundary with the Bengal Delta Plain. About
      30,000 people residing in 30 villages and towns are directly exposed to arsenic
      and more than 200,000 people are "at risk." Complete geographical extent of this
      contamination is being established, and this newly reported contaminated area
      could be quite large. This paper further reports that the mechanisms involved in
      arsenic mobilisation are complex and the two theories of arsenic mobilisation,
      i.e., pyrite oxidation and oxyhydroxides reduction, do not fully explain the high
      levels of arsenic contamination. This paper also proposes the "oxidation
      reduction theory" for arsenic mobilisation where the arsenic originates from the
      arsenopyrite oxidation and the arsenic thus mobilised forms the minerals and gets
      reduced underground in favourable Eh conditions. The stoppage of water withdrawal
      from the contaminated sources did not result in lowering of arsenic levels as
      expected according to the heavy groundwater extraction theory (pyrite oxidation
      theory). Cases of arsenicosis in the region are on the rise and the switchover to
      less contaminated water has not reversed the arsenicosis progression in the
      affected persons even after 2 years. Surface water of the rivers is also being
      contaminated because of the probable dislocation of contaminated groundwater due
      to the heavy rains in monsoon season, which indicates that the river water could
      be a major carrier of arsenic in dissolved or adsorbed forms that may be a cause
      of contamination of the delta plains.

PMID- 12220111
TI  - Scenario-model-parameter: a new method of cumulative risk uncertainty analysis.
AB  - The recently developed concepts of aggregate risk and cumulative risk rectify two
      limitations associated with the classical risk assessment paradigm established in
      the early 1980s. Aggregate exposure denotes the amount of one pollutant available
      at the biological exchange boundaries from multiple routes of exposure.
      Cumulative risk assessment is defined as an assessment of risk from the
      accumulation of a common toxic effect from all routes of exposure to multiple
      chemicals sharing a common mechanism of toxicity. Thus, cumulative risk
      constitutes an improvement over the classical risk paradigm, which treats
      exposures from multiple routes as independent events associated with each
      specific route. Risk assessors formulate complex models and identify many
      realistic scenarios of exposure that enable them to estimate risks from exposures
      to multiple pollutants and multiple routes. The increase in complexity of the
      risk assessment process is likely to increase risk uncertainty. Despite evidence
      that scenario and model uncertainty contribute to the overall uncertainty of
      cumulative risk estimates, present uncertainty analysis of risk estimates
      accounts only for parameter uncertainty and excludes model and scenario
      uncertainties. This paper provides a synopsis of the risk assessment evolution
      and associated uncertainty analysis methods. This evolution leads to the concept
      of the scenario-model-parameter (SW) cumulative risk uncertainty analysis method.
      The SMP uncertainty analysis is a multiple step procedure that assesses
      uncertainty associated with the use of judiciously selected scenarios and models
      of exposure and risk. Ultimately, the SMP uncertainty analysis method compares
      risk uncertainty estimates determined using all three sources of uncertainty with
      conventional risk uncertainty estimates obtained using only the parameter source.
      An example of applying the SMP uncertainty analysis to cumulative risk estimates
      from exposures to two pesticides indicates that inclusion of scenario and model
      sources.

PMID- 12220112
TI  - Partitioning of metals in sediments from the Odiel River (Spain).
AB  - The Odiel River runs through an area known as the Iberian pyrite belt in the
      province of Huelva in the southwestern corner of the Iberian Peninsula. Its
      waters are acidic and contain large amounts of heavy metals from erosion and
      mining activity. In addition, the Odiel River estuary is one of the most
      industrialized areas in southern Spain and, consequently, receives the discharge
      of industrial and urban waste. Seventeen sediment samples from the Odiel and its
      main tributaries were analyzed for this study. The chemical partitioning of
      metals (Cu, Zn, Cd, Pb, Fe, Ni, Cr and Co) in each sample was determined in four
      fractions (acid-soluble, reducible, oxidizable and residual). The total content
      of each of the metals was also determined. The results showed high concentrations
      of Fe, Cu, Zn, Pb and Cd, undoubtedly as a result of contamination from the
      mining and industrial activity mentioned above. However, the concentrations of
      the other metals analyzed were low since there are no sources of pollution by
      them in the Odiel River. Based on the chemical distribution of metals, we found
      that Cd, Zn and Cu are the most mobile metals (i.e., metals that can pass easily
      into the water under changing environmental conditions). Cd is the metal that
      showed the highest percentages in the acid-soluble fraction (the most labile) and
      the lowest in the residual fraction. However, Pb, Fe, Cr and Ni are present in
      the greatest percentages in the residual fraction, which implies that these
      metals are strongly linked to the sediments.

PMID- 12220113
TI  - Monitoring of cadmium in "on" and "off" date palms.
AB  - The study demonstrated that the mature dates we investigated were considered safe
      for human consumption. However, our findings revealed that much of the early
      fruit and leaves, which appeared at the advent of the fruiting season, possessed
      elevated levels of cadmium (Cd) that could accumulate in the food chain and thus
      impact adversely on the environment. In addition, animal feed for livestock
      contains date leaves, which should be restricted to the mature ones. The
      monitoring of cadmium in date palms is of considerable interest to environmental
      science and the thrust of this work, therefore, involved measurement, by ICP, of
      Cd in dates and corresponding leaf specimens, and evaluation of its distribution
      during the developmental stages of the fruiting season. Thirty-six date samples
      and 36 leaf specimens of the Fard cultivar were collected from "on" and "off"
      date palms during the Kimri, Bisir and Rutab stages of the fruiting season and
      subjected to suitable digestion procedures. Sample masses of typically 1 g (dry
      weight) were prepared in 25 ml dilute acid solution and investigated for trace
      levels of Cd by ICP-AES. Special attention was paid to contamination and the
      validation of our methodology. The Cd "threshold" in our study was 50 ng/g, in
      keeping with the levels of tolerance appearing in the literature. For the dates
      we found elevated levels of Cd [> 50 ng/g] in most of the samples, for both
      categories of "on" and "off" trees, during the Kimri stage. In the case of the
      leaves, the "on" samples revealed significant values up to 125 ng/g in Bisir, in
      some cases, but the trend for the "off" trees remained the same with the highest
      levels [> 100 ng/g] recorded during Kimri. Safe levels were attained during Rutab
      for all specimens. The possibility of a connection between Cd toxicity and the
      alternate-bearing phenomenon is discussed and this could be the subject of future
      interest.

PMID- 12220114
TI  - Selection of a suitable mobile phase for the speciation of four arsenic compounds
      in drinking water samples using ion-exchange chromatography coupled to
      inductively coupled plasma mass spectrometry.
AB  - The performance of two mobile phase buffers, phosphate and TRIS, were compared
      for the speciation of four arsenic species: arsenate (As(V)), arsenite (As(III)),
      mono methylarsonic acid (MMA), and dimethyl arsinic acid (DMA) in drinking water,
      using ion-exchange chromatography inductivelycoupled plasma mass spectrometry
      (IEC-ICP-MS). The mobile phase containing TRIS acetate buffer ("TRIS")
      demonstrated superior perfomance in baseline separation of all four arsenic
      species and the internal standard. It is also applicable to high-throughput
      sample analysis as it minimized the frequency required to clean the sampling
      interface due to salt build-up when compared to the phosphate mobile phase. The
      method was evaluated for its precision, accuracy, linearity and detection limits.
      The method was successfully applied for the analysis of drinking water samples.

PMID- 12220115
TI  - Naphthalene and beta-naphthoflavone effects on Anguilla anguilla L. hepatic
      metabolism and erythrocytic nuclear abnormalities.
AB  - The effects of a polycyclic aromatic hydrocarbon (PAH) such as naphthalene (NAP)-
      an environmental contaminant--and beta-naphthoflavone (BNF)--a model substance
      (PAH-like compound)--were investigated in European eel (Anguilla anguilla L.)
      over 3-, 6-, and 9-day exposure (0.1-2.7 microM). Both xenobiotics revealed to be
      strong biotransformation (phase I) inducers. After 3-day exposure, liver
      ethoxyresorufin O-deethylase (EROD) activity was significantly increased by all
      NAP and BNF tested concentrations. At 6 and 9 days, liver EROD activity was
      significantly induced mainly by the highest NAP and BNF concentrations. Liver
      cytochrome P450 content was significantly induced after 3-day exposure to 0.9 and
      2.7 microM BNF and 9-day exposure to 0.1, 0.3 and 0.9 microM NAP. Liver alanine
      transaminase (ALT) activity was measured as an indicator of hepatic health
      condition, revealing a significant decrease after 6-day exposure to 0.9 microM
      BNF. Genotoxicity measured as erythrocytic nuclear abnormalities (ENA) was
      detected in all BNF treated fish on day 6, whereas on day 9, ENA frequencies
      returned to control levels, significantly decreasing at 0.9 microM BNF exposure.
      Immature erythrocytes (IE) frequency demonstrated a decreasing tendency along the
      BNF experiment and concomitantly with the above ENA response. The present
      experimental results elect EROD activity in A. anguilla as a useful short- to
      medium-term biomarker of exposure to both PAH and PAH-like compounds. However,
      some problems can emerge in the presence of high xenobiotic concentrations.
      Concerning genotoxicity, it is hypothesized that ENA response depends on
      different factors such as the exhaustion of the detoxification process, the
      balance erythropoiesis/erythrocytic catabolism and the DNA repairing capacity.

PMID- 12220116
TI  - Minor and trace elements in the shell of Patella aspera (Roding 1798).
AB  - Specimens of the limpet Patella aspera were collected from a clean, coastal
      marine site and a contaminated estuary on the south coast of Portugal. The shells
      were analysed individually for their minor (Mg, Sr) and trace element (Fe, Mn,
      Zn) content. Mean concentrations of these elements in the shell of P. aspera were
      4651, 1318, 35.8, 29.9 and 5.5 microg g(-1), respectively. The elemental
      concentrations exhibited both a marked intra- and inter-population variability.
      Despite the variability within individual populations, significant differences in
      the trace element composition were apparent between the shells taken from the two
      sites. Small shells (< 2 g) provided the best resolution between sites for both
      manganese and iron. Differences in zinc were best resolved for larger shells. The
      shell of P. aspera has an extraordinarily high magnesium concentration, which is
      insensitive to gross salinity differences, and a trace metal assemblage that can
      be interpreted in terms of environmental exposure. On these grounds, it is
      recommended that the shell of P. aspera is a tissue for potential use in
      environmental trace metal monitoring.

PMID- 12220117
TI  - Polynuclear aromatic hydrocarbons, phenols, and trace metals in selected soil
      profiles and plant bioindicators in the Holy Cross Mountains, south-central
      Poland.
AB  - This report presents the results of PAH, phenol, and selected trace element (Cd,
      Cu, Hg, Pb, S, and Zn) determinations on detailed soil profiles and associated
      plant bioindicators (including lichen Hypogymnia physodes, moss Hylocomium
      splendens, pine Pinus sylvetris) from the three most representative habitats in
      the Holy Cross Mts, south-central Poland. This study is only part of a larger
      ongoing environmental study that includes complex sulfur isotope and element
      determinations in three national parks in N, central and S parts of Poland. The
      highest concentrations of PAHs (1887 ppb) and numerous trace elements are found
      in the organic horizon-O and humic horizon-A of each soil type. Different plant
      species and their individual tissues reveal considerable variability in the
      concentration of PAHs, phenols and elements examined. Most of the H. physodes
      thalli also reveal higher concentrations of individual hydrocarbons and some
      elements (including S and Zn) than their host bark. The highest concentration
      levels of phenols (1217 ppb) are noted in the 1-year pine needles. Most of the
      PAHs and elements examined seem to be of anthropogenic origin. The only exception
      is the distribution pattern of elements in southwestern part of the study area,
      which is linked to the local bedrock geochemical anomaly. The results of this
      study indicate that the content of PAHs, Cd, Cu, Hg, Pb, S and Zn in the soils
      and plant bioindicators examined has not changed considerably since 1998.

PMID- 12220118
TI  - Determination of lead, chromium and zinc in sediments from an urbanized river in
      Mauritius.
AB  - The mean concentration of Cr (105 +/- 30 mg kg(-1)), Zn (167 +/- 30 mg kg(-1))
      and Pb (14 +/- 7 mg kg(-1)) in the sediments along St. Louis River situated in an
      urbanized and industrialized area in Mauritius were well below the limits of 600,
      2500 and 700 mg kg(-1) quoted for contaminated sediments adopted from the draft
      standards (24% clay and 10% organic matter by weight) from the Netherlands [Van
      Veen RJ, Stortelder PBM. Research on contaminated sediments in the Netherlands.
      In: Wolf K, Van de Brink WJ, Colon FJ, editors. Contaminated soil. Academic
      Publisher, 1998. p. 1263-1275.]. Industrial contamination appeared to undergo
      rapid dilution in the estuary as Cr had high levels near point sources from
      industries, but decreased rapidly in amount in the estuary possibly because of
      dilution by other sediments. The significant levels of Zn in sediments from
      upstream to the estuary suggest that the potential sources could be from the
      adjacent motorway and road runoff causing significant quantities to be trapped
      within the St. Louis River. Pb was two folds higher in the sediments in the
      estuary of St. Louis River compared to upstream and downstream indicating
      accumulation of Pb in estuarine sediments, which could be released continuously
      into the lagoon. The potential sources of Pb in sediments from upstream to the
      estuary were from the adjacent motorway and road runoff causing significant
      quantities to be trapped within the St. Louis River. Pb and Zn were significantly
      positively correlated in the sediments along St. Louis River indicating a common
      source for Pb and Zn. Significant negative correlations were also found for both
      Pb and Zn with dissolved oxygen in summer along St. Louis River which indicated
      that the presence of anoxic waters influenced the trapping of Zn and Pb in the
      sediment phase. This study has also highlighted that a phasedown of Pb in petrol
      is necessary and with the introduction of unleaded petrol and vehicles equipped
      with catalytic converters, studies on levels of Pd and Pt to provide baseline
      data need to be done in the near future and integrated in environmental
      development schemes and effective coastal zone management of small island states.

PMID- 12220119
TI  - Distribution of Cd, Cu, Fe, Mn, Pb and Zn in selected tissues of juvenile whales
      stranded in the SE Gulf of California (Mexico).
AB  - With the aim of knowing the concentration and distribution of essential and
      nonessential metals in selected tissues of whales, analysis of Cd, Cu, Fe, Mn, Pb
      and Zn were carried out in kidney, liver and muscle of the gray whale
      Eschrichtius robustus and the sperm whale Physeter catodon. Whales were found
      stranded in the southeast Gulf of California. Individuals were in a juvenile
      stage; mean length of whales was 9.3 m for E. robustus and 7 m for P. catodon.
      Sequence of metal concentrations was Fe>Zn>Cu>Mn>Cd>Pb in E. robustus, and
      Fe>Zn>Cu>Cd>Mn>Pb in P. catodon. In E. robustus, highest concentrations of Cu,
      Mn, Pb and Zn (17.2, 19.6, 0.9 and 388 microg g(-1), respectively) were measured
      in liver, Cd (5.7 microg g(-1)) in kidney and Fe (1009 microg g(-1)) in muscle.
      In P. catodon, the highest levels of Cu, Fe and Pb (48.6, 5200 and 4.2 microg g(
      1), respectively) were found in liver, Cd and Zn (94 and 183 microg g(-1)) in
      kidney and Mn (8 microg g(-1)) in muscle. Metal concentrations reported here were
      not considered to contribute to the stranding of specimens.

PMID- 12220120
TI  - Ultrastructure of the placenta of the tammar wallaby, Macropus eugenii:
      comparison with the grey short-tailed opossum, Monodelphis domestica.
AB  - The ultrastructure of the tammar placenta was studied throughout pregnancy. The
      uterine epithelium grows from a columnar to an enlarged, undulating epithelium
      between early gestation and mid-gestation when the shell coat that surrounds the
      marsupial conceptus ruptures. Trophectoderm and uterine epithelium do not form
      syncytia, nor does invasion of the endometrium occur at any stage of pregnancy.
      Uterine secretion is provided to both the bilaminar and the trilaminar side of
      the yolk sac placenta up to birth. Fenestrations, abundant vesicles and lumenal
      processes of maternal capillaries, as well as deep basal folds of the uterine
      epithelium, suggest that there is transfer of hemotrophes adjacent to both parts
      of the yolk sac. In contrast, in the grey short-tailed opossum, these structures
      are lacking. The yolk sacs of adjacent embryos fuse to form a common yolk sac
      cavity, thus losing most of the bilaminar yolk sac. The bilaminar and trilaminar
      components of the yolk sac placenta of the tammar are less different in structure
      and function than those of the grey short-tailed opossum, but both types are
      fully functional placentas. The extended secretory phase of the tammar uterus and
      the maternal recognition of early pregnancy appear to be derived characters of
      macropodid marsupials.

PMID- 12220122
TI  - Expression of parathyroid hormone-related peptide (PthrP) and its receptor
      (PTH1R) during the histogenesis of cartilage and bone in the chicken mandibular
      process.
AB  - The purpose of this study was to examine the expression and actions of
      parathyroid hormone-related protein (PTHrP) when skeletal histogenesis occurs in
      the chicken mandible. Prior to the appearance of skeletal tissues, PTHrP and
      PTH1R were co-expressed by cells in the ectoderm, skeletal muscle, peripheral
      nerve and mesenchyme. Hyaline cartilage was first observed at HH stage 27 when
      many but not all chondroblasts expressed PTHrP and PTH1R. By stage 34, PTHrP and
      PTH1R were not detected in chondrocytes but were expressed in the perichondrium.
      Alkaline phosphatase (AP)-positive preosteoblasts and woven bone appeared at
      stages 31 and 34, respectively. Preosteoblasts, osteoblasts and osteocytes co
      expressed PTHrP and PTH1R. Treatment with chicken PTHrP (1-36) increased cAMP in
      mesenchyme from stage 26 embryos. Continuous exposure to chicken PTHrP (1-36) for
      14 days increased cartilage nodule number and decreased AP while intermittent
      exposure did not affect cartilage nodule number and increased AP in cultures of
      stage 26 mesenchymal cells. Adding a neutralizing anti-PTHrP antibody to the
      cultures reduced cartilage nodule number and did not affect AP. These findings
      show that PTHrP and PTH1R are co-expressed by extraskeletal and skeletal cells
      before and during skeletal tissue histogenesis, and that PTHrP may influence
      skeletal tissue histogenesis by affecting the differentiation of mandibular
      mesenchymal cells into chondroblasts and osteoblasts.

PMID- 12220121
TI  - The role of mitochondria, cytochrome c and caspase-9 in embryonic lens fibre cell
      denucleation.
AB  - During the differentiation of secondary lens fibre cells from the lens
      epithelium, the fibre cells lose all of their cytoplasmic organelles as well as
      their nuclei. The fibre cells, containing crystallins, which confer optical
      clarity, then persist in the adult lens. The process of denucleation of these
      cells has been likened to an apoptotic event which is not followed by the plasma
      membrane changes that are characteristic of apoptosis. We have examined the
      expression and subcellular translocation of molecules of the apoptotic cascade in
      differentiating lens epithelial cells in culture. In this culture system, the
      epithelial cells differentiate into lentoids composed of lens fibre cells. We
      find that caspase-9, which is expressed and activated before embryonic day 12 in
      intact lenses, is localized in the cytosol outside mitochondria in non
      differentiating cultured cells. In lentoid cells, caspase-9 migrates into
      mitochondria after the latter undergo a membrane permeability transition that is
      characteristic of apoptotic cells. At the same time, caspase-9 co-localizes with
      cytochrome c in the cytosol. The cytochrome c is apparently released from the
      mitochondria in lentoid cells after the mitochondrial membrane permeability
      transition and during the period of nuclear shrinkage. Also during this time, the
      mitochondria aggregate around the degenerating nuclei. Cytochrome c disappears
      rapidly, while mitochondrial breakdown occurs approximately coincident with the
      disappearance of the nuclei, but mitochondrial remnants persist together with
      cytochrome c oxidase, which is a mitochondrial marker protein. Apaf-1, another
      cytosolic protein of the apoptotic cascade, also migrates to the permeabilized
      mitochondria and also co-localizes with caspase-9 and cytochrome c in the cytosol
      or mitochondria of denucleating cells, thus providing evidence for the formation
      of an 'apoptosome' in these cells, as in apoptotic cells. At no time did we
      observe the translocation of molecules between cytoplasmic compartments and the
      nucleus in differentiating lentoid cells. We suggest that the uncoupling of
      nuclear and membrane apoptotic events in these cells may be due to the early
      permeability changes in the mitochondria, resulting in the loss of mitochondrial
      signalling molecules, or to the failure of molecules to migrate to the nucleus in
      these cells, thus failing to activate nuclear-plasma membrane signalling
      pathways.

PMID- 12220123
TI  - Expression of VEGF121 and VEGF165 in hypertrophic chondrocytes of the human
      growth plate and epiphyseal cartilage.
AB  - Vascular endothelial growth factor (VEGF) plays an important role during
      endochondral bone formation in hypertrophic cartilage remodelling. We examined
      VEGF and VEGF receptor expression in tibiae from fetuses, newborns and children
      immunohistochemically. Expression of mRNA for the different VEGF splice forms and
      for VEGF receptors KDR and FLT-1 was analysed by reverse transcription-polymerase
      chain reaction (RT-PCR). VEGF could be immunolocalized intracellularly in the
      hypertrophic chondrocytes of the growth plate and in the chondrocytes around
      cartilage canals of the epiphysis, respectively. The resting zone and the
      proliferative zone of the growth plate were VEGF-negative. In cartilage samples
      of all growth plates analysed, VEGF121 and VEGF165 were identified as the only
      VEGF splice forms expressed. RT-PCR for VEGF mRNA of normal hyaline cartilage was
      negative. At vessels growing into the hypertrophic cartilage FLT-1 (VEGFR-1) and
      KDR (VGEFR-2) could be visualized. Reverse transcription-polymerase chain
      reaction (RT-PCR) substantiated the results regarding FLT-1 and KDR expression.
      The results of our study suggest that the splice forms VEGF121 and VEGF165 and
      the receptors KDR and FLT-1 of the known angiogenetic peptide VEGF play a role in
      process of endochondral ossification.

PMID- 12220124
TI  - Regional variations in the cellular matrix of the annulus fibrosus of the
      intervertebral disc.
AB  - The three-dimensional architecture of cells in the annulus fibrosus was studied
      by a systematic, histological examination using antibodies to cytoskeletal
      components, in conjunction with confocal microscopy. Variations in cell shape,
      arrangement of cellular processes and cytoskeletal architecture were found both
      within and between the defined zones of the outer and inner annulus. The
      morphology of three, novel annulus fibrosus cells is described: extended cordlike
      cells that form an interconnected network at the periphery of the disc; cells
      with extensive, sinuous processes in the inner region of the annulus fibrosus;
      and cells with broad, branching processes specific to the interlamellar septae of
      the outer annulus. The complex, yet seemingly deliberate arrangement of various
      cell shapes and their processes suggests multiple functional roles. Regional
      variations in the organization of the actin and vimentin cytoskeletal networks is
      reported across all regions of the annulus. Most notable is the continuous,
      strand arrangement of the actin label at the disc's periphery in contrast to its
      punctate appearance in all other regions. The gap junction protein connexin 43
      was found within cells from all regions of the annulus, including those which did
      not form physical connections with surrounding cells. These observations of the
      cellular matrix in the healthy intervertebral disc should contribute to a better
      understanding of site-specific changes in tissue architecture, biochemistry and
      mechanical properties during degeneration, injury and healing.

PMID- 12220126
TI  - A quantitative analysis of perineurial cell basement membrane collagen IV,
      laminin and fibronectin in diabetic and non-diabetic human sural nerve.
AB  - The thickness of the perineurial cell basement membrane was examined in diabetic
      and non-diabetic human sural nerve. A significant increase in thickness was found
      in the diabetic group. The nature of this thickening was investigated using
      immunohistochemistry and image analysis in order to semi-quantify three of the
      major intrinsic components of the perineurial cell basement membrane: collagen
      IV, laminin and fibronectin. Amounts of all three components were shown to be
      increased in the diabetic group, but not significantly so. However, significant
      linear correlations between fascicle size and perineurial collagen IV, laminin
      and fibronectin were identified in both diabetic and non-diabetic nerve.

PMID- 12220125
TI  - Transforming growth factor-beta 2 heterozygous mutant mice exhibit Cowper's gland
      hyperplasia and cystic dilations of the gland ducts (Cowper's syringoceles).
AB  - Analyses of mutant mice with a deletion for the transforming growth factor beta 2
      (Tgfbeta2) gene revealed cysts in the perineal/scrotal region of male mice. We
      present evidence from in situ, light and electron microscopy that the cysts
      observed in Tgfbeta2+/- heterozygous mice males derive from Cowper's gland
      tissue. The Cowper's glands of Tgfbeta2+/- heterozygous mutant mice display all
      steps of glandular hyperplasia and cystic dilation. TGF-beta isoforms and TGF
      beta receptor (TbetaR-II) were localized immunocytochemically in sections of
      Cowper's glands. TGF-beta2 and TGF-beta3 were located predominantly in
      myoepithelial cells of the Cowper's gland whereas the TbetaRII was found in the
      plasma membrane of the acinar cells. TUNEL-assays revealed that apoptotic cell
      death is significantly reduced in Cowper's glands of TgfbetaB2+/- heterozygous
      mutant mice. The fact that Tgfbeta2+/- heterozygous mutant mice exhibit
      hyperplasia of Cowper's gland epithelium and Cowper's gland cysts suggests a
      disturbance of epithelial-stromal interaction most likely due to reduced TGF
      beta2 level, accompanied by a significant decrease in apoptosis.

PMID- 12220127
TI  - Lack of detectable genetic recombination on the X chromosome during the
      parthenogenetic production of female and male aphids.
AB  - We used polymorphic microsatellite markers to look for recombination during
      parthenogenetic oogenesis between the X chromosomes of aphids of the tribe
      Macrosiphini. We examined the X chromosome because it comprises approximately 25
      % of the genome and previous cytological observations of chromosome pairing and
      nucleolar organizer (NOR) heteromorphism suggest recombination, although the same
      is not true for autosomes. A total of 564 parthenogenetic females of Myzus clones
      with three distinct reproductive modes (cyclical parthenogenesis, obligate
      parthenogenesis and obligate parthenogenesis with male production) were genotyped
      at three informative X-linked loci. Also, parthenogenetically produced males from
      clones encompassing the full range of male-producing reproductive strategies were
      genotyped. These included 391 Myzus persicae males that were genotyped at three X
      linked loci and 538 males from Sitobion clones that were genotyped at five
      informative X-linked loci. Our results show no departure from clonality in
      parthenogenetic generations of aphids of the tribe Macrosiphini: no recombinant
      genotypes were observed in parthenogenetically produced males or females.

PMID- 12220128
TI  - Association of single-nucleotide polymorphisms at the Delta locus with genotype
      by environment interaction for sensory bristle number in drosophila Melanogaster.
AB  - The nature of forces maintaining variation for quantitative traits can only be
      assessed at the level of individual genes affecting variation in the traits.
      Identification of single-nucleotide polymorphisms (SNPs) associated with
      variation in Drosophila sensory bristle number at the Delta (Dl) locus provides
      us with the opportunity to test a model for the maintenance of variation in
      bristle number by genotype by environment interaction (GEI). Under this model,
      genetic variation is maintained at a locus under stabilizing selection if
      phenotypic values of heterozygotes are more stable than homozygotes across a
      range of environments, and the mean allelic effect is much smaller than the
      standard deviation of allelic effects across environments. Homozygotes and
      heterozygotes for two SNPs at Dl, one affecting sternopleural and the other
      abdominal bristle number, were reared in five different environments. There was
      significant GEI for both bristle traits. Neither condition of the model was
      satisfied for Dl SNPs exhibiting GEI for sternopleural bristle number.
      Heterozygotes for the abdominal bristle number SNPs were indeed the most stable
      genotype for two of the three environment pairs exhibiting GEI, but the mean
      genotypic effect was greater than the standard deviation of effects across
      environments. Therefore, this mechanism of GEI seems unlikely to be responsible
      for maintaining the common bristle number polymorphisms at Dl.

PMID- 12220129
TI  - Effects of seed dispersal on spatial genetic structure in populations of
      Rutidosis leptorrhychoides with different levels of correlated paternity.
AB  - Rutidosis leptorrynchoides is a perennial forb endemic to grasslands and grassy
      woodlands in southeastern Australia. Studies of seed dispersal, spatial genetic
      structure and clonality were carried out in four populations around the Canberra
      region that varied in levels of correlated paternity to examine: (1) whether R.
      leptorrhynchoides populations exhibit fine-scale spatial genetic structure and
      whether this varies between populations as a function of correlated paternity;
      (2) whether there is a correlation between seed dispersal distance and genetic
      relatedness within populations; and (3) whether clonal reproduction occurs in
      this species and to what degree this could account for the observed spatial
      genetic structure. The results show that there is variation in the magnitude and
      extent of spatial genetic structure between R. leptorrhynchoides populations. The
      three larger populations, with low to moderate full-sib proportions, showed
      significant patterns of coancestry between plants over scales of up to one metre,
      whereas the smallest population, with a high full-sib proportion, had erratically
      high but non-significant coancestry values. The observed patterns of genetic
      clumping could be explained by a combination of limited seed dispersal and
      correlated mating owing to limited mate availability resulting from the species'
      sporophytic self-incompatibility system. Clonality does not appear to be an
      important factor contributing to genetic structure in this species.

PMID- 12220130
TI  - Sibship reconstruction in hierarchical population structures using Markov chain
      Monte Carlo techniques.
AB  - Markov chain Monte Carlo procedures allow the reconstruction of full-sibships
      using data from genetic marker loci only. In this study, these techniques are
      extended to allow the reconstruction of nested full- within half-sib families,
      and to present an efficient method for calculating the likelihood of the observed
      marker data in a nested family. Simulation is used to examine the properties of
      the reconstructed sibships, and of estimates of heritability and common
      environmental variance of quantitative traits obtained from those populations.
      Accuracy of reconstruction increases with increasing marker information and with
      increasing size of the nested full-sibships, but decreases with increasing
      population size. Estimates of variance component are biased, with the direction
      and magnitude of bias being dependent upon the underlying errors made during
      pedigree reconstruction.

PMID- 12220131
TI  - A logistic mixture model for characterizing genetic determinants causing
      differentiation in growth trajectories.
AB  - The logistic or S-shaped curve of growth is one of the few universal laws in
      biology. It is certain that there exist specific genes affecting growth curves,
      but, due to a lack of statistical models, it is unclear how these genes cause
      phenotypic differentiation in growth and developmental trajectories. In this
      paper we present a statistical model for detecting major genes responsible for
      growth trajectories. This model is incorporated with pervasive logistic growth
      curves under the maximum likelihood framework and, thus, is expected to improve
      over previous models in both parameter estimation and inference. The power of
      this model is demonstrated by an example using forest tree data, in which
      evidence of major genes affecting stem growth processes is successfully detected.
      The implications for this model and its extensions are discussed.

PMID- 12220132
TI  - A method for computing identity by descent probabilities and quantitative trait
      loci mapping with dominant (AFLP) markers.
AB  - Amplified fragment length polymorphisms (AFLPs) are a widely used marker system:
      the technique is very cost-effective, easy and rapid, and reproducibly generates
      hundreds of markers. Unfortunately, AFLP alleles are typically scored as the
      presence or absence of a band and, thus, heterozygous and dominant homozygous
      genotypes cannot be distinguished. This results in a significant loss of
      information, especially as regards mapping of quantitative trait loci (QTLs). We
      present a Monte Carlo Markov Chain method that allows us to compute the identity
      by descent probabilities (IBD) in a general pedigree whose individuals have been
      typed for dominant markers. The method allows us to include the information
      provided by the fluorescent band intensities of the markers, the rationale being
      that homozygous individuals have on average higher band intensities than
      heterozygous individuals, as well as information from linked markers in each
      individual and its relatives. Once IBD probabilities are obtained, they can be
      combined into the QTL mapping strategy of choice. We illustrate the method with
      two simulated populations: an outbred population consisting of full sib families,
      and an F2 cross between inbred lines. Two marker spacings were considered, 5 or
      20 cM, in the outbred population. There was almost no difference, for the
      practical purpose of QTL estimation, between AFLPs and biallelic codominant
      markers when the band density is taken into account, especially at the 5 cM
      spacing. The performance of AFLPs every 5 cM was also comparable to that of
      highly polymorphic markers (microsatellites) spaced every 20 cM. In economic
      terms, QTL mapping with a dense map of AFLPs is clearly better than
      microsatellite QTL mapping and little is lost in terms of accuracy of position.
      Nevertheless, at low marker densities, AFLPs or other biallelic markers result in
      very inaccurate estimates of QTL position.

PMID- 12220134
TI  - Universal leucocyte reduction of blood components: a need for evidence-based
      decision making.
AB  - By the time this chapter is published, the majority of western based transfusion
      services will probably have mandated universal leucocyte reduction (ULR) as a
      requirement for blood components. This measure, which has entered the transfusion
      environment over the past three years, has divided the blood banking community
      like few other issues over its history. To those who, like the author, have been
      aware of the possible benefits of leucocyte reduction for many years, the rush
      towards the universal implementation of a very expensive measure has resulted in
      a sense of bemusement rather than otherwise. This chapter does not seek to
      replicate the many excellent reviews outlining the pros and cons of this issue.
      Rather, active consideration of evidence-based leucocyte reduction is proposed
      against a background of the possibilities imposed by the logistics and
      constraints which current transfusion medicine experiences.

PMID- 12220133
TI  - Application of non-parametric bootstrap methods to estimate confidence intervals
      for QTL location in a beef cattle QTL experimental population.
AB  - Empirical confidence intervals (CIs) for the estimated quantitative trait locus
      (QTL) location from selective and non-selective non-parametric bootstrap
      resampling methods were compared for a genome scan involving an Angus x Brahman
      reciprocal fullsib backcross population. Genetic maps, based on 357
      microsatellite markers, were constructed for 29 chromosomes using CRI-MAP V2.4.
      Twelve growth, carcass composition and beef quality traits (n = 527-602) were
      analysed to detect QTLs utilizing (composite) interval mapping approaches. CIs
      were investigated for 28 likelihood ratio test statistic (LRT) profiles for the
      one QTL per chromosome model. The CIs from the non-selective bootstrap method
      were largest (87 7 cM average or 79-2% coverage of test chromosomes). The
      Selective II procedure produced the smallest CI size (42.3 cM average). However,
      CI sizes from the Selective II procedure were more variable than those produced
      by the two LOD drop method. CI ranges from the Selective II procedure were also
      asymmetrical (relative to the most likely QTL position) due to the bias caused by
      the tendency for the estimated QTL position to be at a marker position in the
      bootstrap samples and due to monotonicity and asymmetry of the LRT curve in the
      original sample.

PMID- 12220135
TI  - Perspective: haematopoietic stem cell rescue enabling high-dose chemotherapy,
      tool for immunotherapy.

PMID- 12220136
TI  - New developments in biological standardisation: commentary on the poster session
      on advances in transfusion safety.
AB  - The 21 presentations have been arranged into two broad inter-related groups: (i)
      Quality of therapeutic preparations and studies on viral/bacterial inactivation
      procedures. (ii) Diagnostic assays for viral safety and quality control of blood
      components. Furthermore, in line with the main theme of this symposium, I have
      attempted to provide an overview of pertinent continuing investigation of blood
      component safety and supply, the "twin pillars" of transfusion therapy, focusing
      on the three pointers (3Ps) of the quality system-patient, process and product.

PMID- 12220137
TI  - Advances in transfusion safety--2001: the organiser's view.

PMID- 12220138
TI  - Beyond HIV, HBV and HCV--how to deal with other viruses?
AB  - Transmission of viruses such as HBV, HIV and HCV by blood components and protein
      fractions are well documented and precautions based on donor selection and
      screening as well as processing are well established and effective. Other
      viruses, including small non-enveloped viruses, pose a greater challenge for
      removal, but are considered less hazardous clinically. While cell associated
      viruses such as HTLVI and CMV pose a risk to certain kinds of recipient of blood
      components the biggest single current issue is that of vCJD following the BSE
      epidemic in the United Kingdom.

PMID- 12220139
TI  - Status of NAT screening for HCV, HIV and HBV--experiences of the German Red Cross
      Blood Donation Services.

PMID- 12220140
TI  - Status of NAT screening for HCV, HIV and HBV: experience in Japan.
AB  - The first nationwide nucleic acid amplification testing (NAT) for hepatitis B
      virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus type 1
      (HIV-1) of voluntarily donated blood after serological pre-screening and before
      release of cellular components and plasma for fractionation was implemented by
      the Japanese Red Cross Blood Transfusion Services. The NAT screening assay using
      multiplex reagent is time-saving, cost effective, and labour-saving procedure for
      all blood and blood products including short-shelf life platelets. During the 50
      mini-pool NAT screening of serologically negative donations (February 1, 2001
      April 30, 2001), we were able to screen out 112 HBV-positive, 25 HCV-positive,
      and 4 HIV-1 positive units from blood and blood components.

PMID- 12220141
TI  - Transfusion safety, 2001.

PMID- 12220142
TI  - NAT update: where are we today?
AB  - The US blood supply has been tested for HIV-1 and HCV using Nucleic Acid
      Amplification Testing (NAT) of small pools since early in 1999. Since the
      implementation of NAT under an investigational new drug (IND) application, the
      results for yield and false positivity have been amazingly consistent for greater
      than two years of testing even among multiple programmes using two different test
      methodologies and manufacturers: Gen-Probe/Chiron transcription-mediated
      amplification (TMA) and Roche PCR. All programmes in the US and Canada use NAT as
      a criterion for cellular as well as frozen product release. The focus of this
      manuscript is to provide an update of the programmes in the US and Canada,
      provide data in support of p24 antigen replacement by HIV-1 NAT, and discuss the
      projections of residual risk of HIV, HCV and HBV following NAT and the associated
      cost/benefit.

PMID- 12220143
TI  - Incidence and significance of the bacterial contamination of blood components.
AB  - A septic reaction occurring during or following the transfusion of cellular blood
      components was one of the earliest recognized complications of allogeneic blood
      transfusions. The presence of bacteria in blood products has been a problem for
      many decades and currently it is probably the most common microbiological cause
      of transfusion-associated morbidity and mortality. Transfusion-associated sepsis
      due to contaminated platelet concentrates appears to be much more common than
      those due to red cells. The overall prevalence of contaminated cellular blood
      products (red cells and platelets) is approximately one in 3000; however, the
      transfusion to a recipient of a contaminated blood product may not necessarily be
      associated with clinically evident morbidity. This is because the majority of
      contaminated blood product units contain only few bacteria. In other instances,
      contaminated units may contain large numbers of virulent bacteria as well as
      endotoxins, and their transfusion may be associated with significant morbidity
      and even be lethal to the recipient. The prevalence of severe episodes of
      transfusion-associated sepsis has not been clearly established, but is probably
      of the order of one in 50,000 per platelet unit and one in 500,000 per red cell
      unit transfused. As a result of the increased recognition that such transfusion
      associated episodes can occur, a variety of measures have been proposed to try to
      prevent and/or control the risk of transfusion-associated septic reactions.

PMID- 12220144
TI  - Methods to minimize transfusion related bacterial sepsis.

PMID- 12220145
TI  - Epidemiology of variant CJD.
AB  - There are 100 confirmed cases of variant CJD (vCJD) in the U.K., with four cases
      in other countries (France and the Republic of Ireland). In the U.K., The mean
      age of onset is 28 years (range 12-74) with a median duration of 13 months (range
      6-39). There are reported regional variations in incidence in the U.K., with a
      North/South difference and a 'cluster' of cases in one county, Leicestershire.
      The incidence of cases in the U.K. is rising. There are concerns about the
      possibility of secondary, iatrogenic, spread of vCJD, especially given the
      finding of positive PrP immunocytochemistry in lymphoreticular tissue.
      Experimental evidence has confirmed the presence of infectivity in blood in
      transmissible spongiform encephalopathy (TSE) models, but the significance of
      this in relation to human blood practice is uncertain. The accumulated
      epidemiological evidence has not shown blood to be a risk factor for sporadic
      CJD, but variant CJD may behave differently. A Transfusion Medicine
      Epidemiological Review in the U.K. is collecting data on CJD case donors and
      recipients, with negative results to date.

PMID- 12220146
TI  - Haemovigilance: a view of a transfusionist.

PMID- 12220147
TI  - Can prion diseases be transmitted between individuals via blood transfusion:
      evidence from sheep experiments.
AB  - We have shown that it is possible to transmit bovine spongiform encephalitis
      (BSE) to a sheep by transfusion with whole blood taken from another sheep during
      the pre-clinical phase of an experimental BSE infection when the donor animal
      appears healthy. BSE and new variant Creutzfeld-Jakob disease (vCJD) in humans
      are caused by the same infectious agent and the sheep-BSE experimental model has
      similar pathogenesis, with involvement of the lymphoreticular system, to that of
      human vCJD. Although we have had only one case of positive transmission of BSE
      out of a total of 21 transfusions, our studies remain incomplete and further
      cases could occur. Our studies, however, reinforce the possibility that whole
      blood donated by pre-clinical vCJD-infected humans may represent a risk of
      spreading vCJD infection among the human population of the U.K.

PMID- 12220148
TI  - Research strategies for evaluation of prion partitioning in plasma fractionation:
      impact of different forms of prion spike on partitioning behaviour.

PMID- 12220149
TI  - An animal welfare view of wildlife contraception.
AB  - Although there is some dissent, the animal protection community generally
      supports the concept of wildlife contraception. However, some contraceptive
      agents, delivery mechanisms and specific applications will be opposed by animal
      welfare advocates on environmental, humane or other ethical grounds, and some
      animal rights advocates may oppose wildlife contraception entirely. The Humane
      Society of the United States (HSUS) has supported and conducted wildlife
      contraception studies for more than 10 years. In general, we have invested in
      contraceptive agents (such as porcine zona pellucida) that we believe will prove
      environmentally, physiologically and behaviourally benign, and in delivery
      mechanisms that are narrowly targeted. As we consider contraception to be a major
      intervention into natural processes, we believe that wildlife contraception
      should be applied judiciously, locally and in a manner that is sensitive to the
      needs of animals, humans and ecosystem function.

PMID- 12220150
TI  - Placentation in the African elephant, Loxodonta africana. I. Endocrinological
      aspects.
AB  - Placental and fetal tissues were recovered from the uteri of 59 pregnant elephant
      that ranged in estimated age from day 18 to month 21 of gestation. Incubation of
      placenta and fetal gonad, alone or in combination, with tritium-labelled
      cholesterol, pregnenolone and androstenedione failed to yield any labelled
      progestagens or oestrogens from placenta, but did produce small amounts of
      labelled progesterone and 5alpha-dihydroprogesterone from fetal gonad.
      Immunochemical staining of tissues with four antisera specific for enzymes
      involved in the steroidogenic pathway revealed no staining in sections of
      placenta but positive labelling for P450 side chain cleavage enzyme (SCC450) and
      3beta-hydroxysteroid dehydrogenase (3beta-HSD) of the interstitial cells that
      comprise the bulk of the enlarged fetal gonads during the second half of
      gestation. Saline extracts of placental tissue showed no activity in three
      different gonadotrophin assays. In view of this endocrinological inactivity in
      the zonary elephant placenta and the probable reliance on maternal luteal sources
      of progestagens for maintenance of the pregnant state, the argument is advanced
      that uncomplicated abortion would probably follow a single administration of a
      PGF analogue given at any stage of pregnancy. If so, the treatment might
      constitute an efficacious method for controlling population increases in
      elephants maintained in enclosed game parks in Africa.

PMID- 12220151
TI  - Field applications of immunocontraception in African elephants (Loxodonta
      africana).
AB  - The primary aim of the Makalali elephant immunocontraception programme is to test
      the efficacy of porcine zona pellucida (PZP) vaccine for practical population
      control of elephants in small, enclosed reserves, with the goal of stabilizing
      the current growth rate and reducing it to the 5-10% per annum displayed
      currently in the Kruger National Park. A secondary aim is to test the hypothesis
      that PZP treatment does not affect patterns of elephant social behaviour.
      Eighteen sexually mature cows (age > 12 years) were vaccinated in May 2000 using
      remote darts. Behavioural observations before, during and after vaccination
      included noting the activity of individual animals every minute for 15 min. No
      changes in general behaviour patterns have been noted to date although the
      animals' spatial use of the reserve was erratic during the period of vaccination,
      indicating irregular or disturbed patterns associated with vaccination. Normality
      was resumed on completion of the vaccinations. No aggressive or indifferent
      behaviour related to nursing, calf proximity or bull-cow interactions have been
      noted. Ten of the females were in various stages of pregnancy when treated.
      Subsequently, seven of them gave birth to healthy calves and the other three
      females are expected to calve shortly. It is too early in the study to draw
      conclusions about stabilization of growth rates.

PMID- 12220152
TI  - Differences in immunocontraceptive responses in white-tailed deer (Odocoileus
      virginianus) and goats (Capra hircus).
AB  - Thirteen deer (Odocoileus virginianus) and three goats (Capra hircus) were given
      an initial immunization of 300 microg porcine zona pellucida (PZP) combined with
      50 mg synthetic trehalose dicorynomycolate ml(-1) (STDCM) in drakeol i.m. in the
      semitendinosus and semimembranosus muscles. This immunization was followed by two
      booster injections of 300 microg PZP, 2 weeks apart. The vaccinations were made
      from the same purified batch of PZP and lot of adjuvant. All the doses were made
      at the same time and injected on the same day. The immune response was quantified
      by measuring serum anti-PZP IgG antibody concentration by ELISA. The results
      showed that the mean serum IgG concentration of the deer increased from 0.000 +/-
      0.003 to 0.083 +/- 0.023 absorbance units, whereas in the goats the mean IgG
      concentration increase was from 0.044 +/- 0.019 to 1.245 +/- 0.774 absorbance
      units. Both the goats and deer showed a significant increase in IgG concentration
      (P < 0.05) after the final booster injection compared with preimmune serum. The
      final goat IgG concentration was significantly (P < 0.05) higher than that of the
      deer. If PZP and Freund's adjuvant are administered to deer, immunocontraception
      is achieved, but the IgG concentration in the deer in this study did not appear
      to be compatible with immunocontraception.

PMID- 12220153
TI  - Comparative effects of GnRH and porcine zona pellucida (PZP) immunocontraceptive
      vaccines for controlling reproduction in white-tailed deer (Odocoileus
      virginianus).
AB  - Fawning rates and mating behaviour were compared between white-tailed deer
      (Odocoileus virginianus) treated with GnRH and porcine zona pellucida (PZP)
      immunocontraceptive vaccines from 1997 to 2000. Female deer from a herd of 102
      deer at Seneca Army Depot, near Romulus, New York, were treated with prime and
      booster injections of PZP (n = 22) or GnRH vaccine (n = 32), or remained
      untreated as controls (n = 34). During the summers after booster treatment,
      observed fawning rates for adult female deer were similar for both PZP-treated
      (0.10-0.11 fawns per female) and GnRH-treated (0.13-0.22 fawns per female) female
      deer, and were significantly lower (t = -8.93 and t = -9.73; P < or = 0.0005,
      respectively) than those observed for control female deer (1.22-1.38 fawns per
      female). During the second (0.36 fawns per female) and third summers (0.61 fawns
      per female) after the last booster injection, GnRH-treated female deer still
      produced significantly fewer fawns than did the controls (1.38 and 1.31 fawns per
      female, respectively). In one breeding season after treatment, five of 18 (28%)
      females vaccinated with PZP produced fawns, similar to the rate for GnRH-treated
      females (29%). In addition, females treated with GnRH had fewer oestrous cycles
      per female (0.06, P < or = 0.05) than did either control (0.22 cycles per female)
      or PZP-treated deer (0.36 cycles per female). Initial PZP treatment followed by a
      booster dose 5-7 months later reduced fawn production and prolonged the breeding
      season as females repeatedly returned to oestrus, similar to results reported in
      other studies.

PMID- 12220154
TI  - Field testing of immunocontraception on white-tailed deer (Odocoileus
      virginianus) on Fire Island National Seashore, New York, USA.
AB  - Application of contraception for the control of suburban populations of white
      tailed deer (Odocoileus virginianus) has been much debated, but few data are
      available on field applications and even fewer on population effects. Between
      1993 and 1997, 74-164 individually known female deer living on Fire Island, New
      York, USA, were treated remotely with an initial shot of 65 microg porcine zona
      pellucida (PZP) in Freund's complete adjuvant followed by booster injections of
      65 microg PZP in Freund's incomplete adjuvant. Starting in 1996, progressively
      increasing numbers of deer were treated with vaccinating/marking darts. Estimates
      of population density and composition, using distance sampling methods, began in
      1995 in selected portions of the study area. Between 1993 and 1997, fawning rates
      among individually known, treated adult females decreased by 78.9% from
      pretreatment rates. Population density in the most heavily treated area increased
      by 11% per year from 1995 to March 1998 and then decreased at 23% per year to
      October 2000. In 1999-2000 surveys, fawns comprised 13-14% of the total
      population in the most heavily treated area, versus 16-33% in nearby untreated
      areas. These results show that PZP can be delivered effectively to sufficient
      deer to affect population density and composition in some environments, but that
      technical and logistical improvements are needed before contraception can be used
      widely to manage suburban deer populations.

PMID- 12220155
TI  - Effects of GnRH agonist (leuprolide) on reproduction and behaviour in female
      wapiti (Cervus elaphus nelsoni).
AB  - Fertility control offers a potential alternative to traditional methods for
      regulating the growth of overabundant wild ungulate populations. However, current
      technology is limited due to practical treatment application, undesirable side
      effects and economic considerations. A promising non-steroidal, non-immunological
      approach to contraception involves the use of a potent GnRH agonist. Two
      experiments were conducted to evaluate the effectiveness of a GnRH agonist
      (leuprolide) for controlling fertility in captive female wapiti and to assess
      physiological and behavioural side-effects of the treatment. In Expt 1, the
      optimum dose of agonist treatment was determined by measuring serum LH response
      of eight female wapiti to four formulations of leuprolide (0, 45, 90 and 180 mg)
      administered as a subcutaneous (s.c.) bioimplant. In Expt 2, the effects of
      leuprolide on wapiti pregnancy rates, duration of suppression of serum LH and
      progesterone secretion, and short-term behavioural and physiological side-effects
      were evaluated. All concentrations of leuprolide in Expt 1 were equally effective
      in reducing serum LH to non-detectable values throughout the 130 day trial. In
      Expt 2, leuprolide administered before the breeding season was 100% effective at
      preventing pregnancy in treated females. Serum LH and progesterone were reduced
      to baseline values by day 92 and remained at this concentration for 195-251 days
      after treatment, and returned to pretreatment concentrations in the following
      breeding season. Reproductive behaviour rates were similar for treated and
      untreated wapiti for all behaviour categories for both the breeding and post
      breeding seasons. Haematology and blood chemistry parameters of treated and un
      treated females were similar, and seasonal intake and body weight dynamics
      appeared normal. In conclusion, leuprolide is a safe, effective contraceptive
      agent and can potentially suppress fertility in female wapiti for one breeding
      season.

PMID- 12220156
TI  - Use of porcine zona pellucida (PZP) vaccine as a contraceptive agent in free
      ranging tule elk (Cervus elaphus nannodes).
AB  - The potential for the application of porcine zona pellucida (PZP)
      immunocontraception in wildlife population management has been tested over a 15
      year period and promises to provide a useful wildlife management tool. These
      studies have provided evidence indicating that the use of PZP immunocontraception
      in wildlife: (i) is effective at both the physiological and population level (Liu
      et al., 1989; Kirkpatrick et al., 1996; Turner et al., this supplement); (ii) is
      deliverable by remote means (Kirkpatrick et al., 1990; Shideler, 2000); (iii) is
      safe in pregnant animals (Kirkpatrick and Turner, this supplement); (iv) is
      reversible (Kirkpatrick et al., 1991; Kirkpatrick and Turner, this supplement);
      (v) results in no long-term debilitating health problems (Kirkpatrick et al.,
      1995; Turner and Kirkpatrick, this supplement); (vi) has no implications for
      passage through the food chain (Harlow and Lane, 1988); and (vii) is reasonably
      inexpensive (J. F. Kirkpatrick, personal communication). This report presents the
      results of a 5 year study in tule elk (Cervus elaphus nannodes), 3 years of which
      were on the application of PZP immunocontraception to an expanding elk population
      living in a wilderness area of Point Reyes National Seashore in Marin County, CA,
      where hunting is not allowed and culling is not publicly acceptable.

PMID- 12220157
TI  - Porcine zona pellucida (PZP) immunocontraception of wild horses (Equus caballus)
      in Nevada: a 10 year study.
AB  - Porcine zona pellucida (PZP) immunocontraception was investigated for possible
      use in free-roaming wild horses in the western USA. A protocol of two injections
      (3-4 weeks apart) of vaccine lasting 1 year was first used and a single-injection
      controlled-release vaccine of 1 year duration was developed and tested in the
      field. Studies of a presumptive vaccine of 2 year duration were initiated. The
      parameters of anti-PZP antibody titre response, pregnancy testing and offspring
      production were used, and PZP vaccine was found to provide up to 94% infertility
      in free-roaming wild mares. In addition, a single-injection PZP vaccine of 1 year
      duration and containing a controlled-release component of PZP in a polymer matrix
      can provide infertility equivalent to the two-injection PZP vaccine. All the PZP
      vaccine preparations tested were associated with a return to normal fertility
      within 1 year. During the course of these studies, attention was given to
      practical aspects of management application of PZP contraception. Preparation of
      the controlled-release portion of the vaccine in pellets, which fit into the
      needle of a dart or syringe, has simplified vaccine handling and permitted long
      term storage of the controlled-release component. Vaccine delivery is now
      performed using a jabstick on captured mares restrained in a field stock chute
      during routine horse gathers. Provision of a vaccine-training programme has
      maximized personnel safety during vaccine preparation and use.

PMID- 12220158
TI  - Effects of immunocontraception on population, longevity and body condition in
      wild mares (Equus caballus).
AB  - Contraception is becoming a common approach for the management of captive and
      wild ungulates yet there are few data for contraceptive effects on entire
      populations. Management-level treatment of mares with porcine zona pellucida
      (PZP) vaccine resulted in zero population growth of the Assateague Island wild
      horse population within 1 year of initiation of treatment. Contraceptive efficacy
      was 90% for mares treated twice in the first year and annually thereafter. For
      mares given a single initial inoculation, contraceptive efficacy was 78%. The
      effort required to achieve zero population growth decreased, as 95, 83 and 84% of
      all adult mares were treated in each of the first 3 years, compared with 59 and
      52% during the last 2 years. Mortality rates for mares and foals after the
      initiation of management-level treatments decreased below historic and
      pretreatment mortality rates of approximately 5%. Two new age classes have
      appeared among treated animals (21-25 years and > 25 years), indicating an
      increase in longevity among treated animals. Body condition scores for all
      horses, all adult mares and non-lactating mares increased significantly between
      summer 1989 and autumn 1999 but did not change significantly in lactating mares.
      These results provide reliable data for the construction of realistic models for
      contraceptive management of free-roaming or captive ungulate populations.

PMID- 12220159
TI  - Mouse-specific immunocontraceptive polyepitope vaccines.
AB  - Two mouse-specific polyepitope protein antigens comprising different combinations
      of sequences chosen from the mouse fertility antigens zona pellucida proteins 1
      and 3 (ZP1 and ZP3), prolactin, proliferin, granulocyte-macrophage colony
      stimulating factor (GM-CSF), sperm protein SP56 and T-helper cell-stimulating
      epitopes were produced in bacterial protein expression systems. The recombinant
      proteins were fused to maltose binding protein (MBP) and used to immunize female
      mice; their effects on fertility were assessed. Controls were immunized with
      either MBP only or phosphate buffered saline (PBS). One antigen construct (MBP
      polyepitope B), containing mouse-specific epitopes for ZP1, ZP3, SP56 and
      proliferin, significantly reduced the fertility of female BALB/c mice. Fertility
      in this group was decreased by > 40% compared with the MBP control and the number
      of viable embryos was decreased by > 60%. This construct will now be used to
      produce the antigen in a recombinant murine cytomegalovirus for assessment as a
      potential mouse-specific anti-fertility vaccine for use in the control of mice in
      the field.

PMID- 12220160
TI  - Reversibility of action and safety during pregnancy of immunization against
      porcine zona pellucida in wild mares (Equus caballus).
AB  - Contraceptive management of publicly valued wildlife species requires safeguards
      to ensure that these populations are preserved in a healthy state. In addition,
      reversibility of contraceptive effects and safety in pregnant animals are major
      concerns. A population of wild horses has been immunized against porcine zona
      pellucida (PZP) over a 12 year period on Assateague Island National Seashore, MD
      (ASIS). Mares initially received one or two 65 microg inoculations and once a
      year 65 microg booster inoculations, all delivered by dart. All young mares aged
      > 2 years were treated with PZP for 3 consecutive years regardless of whether
      they have bred successfully and they were then removed from treatment until they
      had foaled. All mares vaccinated for 1 or 2 consecutive years became fertile
      again and 69% of mares treated for 3 consecutive years returned to fertility. All
      five mares treated for 4 or 5 consecutive years have also returned to fertility,
      but over longer periods of time. Mares treated for 7 consecutive years have not
      returned to fertility, but several, while still infertile, have started ovulating
      again. There was no difference in survival rates between foals born to treated
      and untreated mares, and PZP treatment of pregnant mares did not affect
      subsequent fertility of their female offspring.

PMID- 12220161
TI  - An overview of the symposium: where have we been and where are we going?

PMID- 12220162
TI  - Ecological basis for fertility control in the house mouse (Mus domesticus) using
      immunocontraceptive vaccines.
AB  - Laboratory studies confirm the potential for fertility control in the house mouse
      Mus domesticus using mouse cytomegalovirus (MCMV) as a vector for an
      immunocontraceptive vaccine. This article presents an overview of key results
      from research in Australia on enclosed and field populations of mice and the
      associated epidemiology of MCMV. The virus is geographically widespread in
      Australia. It also persists in low population densities of mice, although if
      population densities are low for at least a year, transmission of the virus is
      sporadic until a population threshold of approximately 40 mice ha(-1) is reached.
      The serological prevalence of MCMV was high early in the breeding season of four
      field populations. Enclosure studies confirm that MCMV has minimal impact on the
      survival and breeding performance of mice and that it can be transmitted to most
      adults within 10-12 weeks. Other enclosure studies indicate that about two-thirds
      of females would need to be sterilized to provide effective control of the rate
      of growth of mouse populations. If this level is not maintained for 20-25 weeks
      after the commencement of breeding, the mouse population can compensate through
      increased recruitment per breeding female. The findings from this series of
      descriptive and manipulative population studies of mice support the contention
      that MCMV would be a good carrier for an immunocontraceptive vaccine required to
      sustain female sterility levels at or above 65%.

PMID- 12220163
TI  - Induction of contraception in some African wild carnivores by downregulation of
      LH and FSH secretion using the GnRH analogue deslorelin.
AB  - The GnRH analogue deslorelin, in long-acting biocompatible implants, was used as
      a contraceptive in 31 cheetahs (13 females and 18 males), 21 African wild dogs
      (15 females and 6 males), 10 lionesses and four leopards (three females and one
      male). A dose of 12 or 15 mg deslorelin was administered to lions, whereas 6 mg
      deslorelin was administered to the other species. Monitoring consisted of
      observations, measurement of plasma progesterone and testosterone concentrations,
      vaginal cytology and evaluation of semen and sex organs. Deslorelin induced
      contraception in lionesses for 12-18 months, and in female cheetahs and leopards
      for a minimum of 12 months after treatment. Two male cheetahs had no viable
      spermatozoa or detectable plasma testosterone 21 months after treatment with
      deslorelin. Female wild dogs responded less consistently and one bitch conceived
      4 weeks after implantation. However, in nine bitches, mating could be postponed
      until the next breeding season. Male dogs responded consistently and the
      contraception was effective for approximately 12 months. Although lionesses and
      cheetahs may become attractive to males for a few days after treatment, mating
      was not observed. No side-effects or behavioural changes were noted, indicating
      that deslorelin is a safe drug to use for the contraception of the species
      described. Males remain fertile for the first 6 weeks after the insertion of
      implants and should be separated from cyclic females during this period.

PMID- 12220164
TI  - Assessment of cabergoline as a reproductive inhibitor in coyotes (Canis latrans).
AB  - The efficacy of three oral formulations (gelatin capsule, tablet, oil base) and
      five dosages (50, 100, 250, 500, 1000 microg) of cabergoline to disrupt
      reproduction in coyotes (Canis latrans) was evaluated. The type of formulation
      used had no effect on plasma progesterone and prolactin concentrations or on mean
      litter size. No adverse side effects (for example, vomiting, anorexia, diarrhoea)
      were observed despite the use of doses of up to 20 times the therapeutic dose
      used for domestic dogs and cats. All coyotes treated with 50, 100, 250 and 500
      microg cabergoline whelped, but plasma progesterone concentrations in these
      coyotes were lower (P < or = 0.07) than in control animals at day 7 after
      treatment. Ten of 11 females treated with 1000 microg cabergoline whelped, but
      progesterone concentrations in these coyotes were lower than in control animals
      up to day 14 after treatment (P < or = 0.04). Dosages of 1000 microg cabergoline
      decreased blood serum prolactin (P < or = 0.10) and progesterone (P < or = 0.06)
      concentrations, but apparently failed to decrease progesterone below the
      threshold necessary to maintain pregnancy in all but one animal. However,
      progressive inhibition of prolactin and progesterone with increasing doses of
      cabergoline indicated that higher dosages might be effective in coyotes. Survival
      of pups born to cabergoline-treated females was not different (P < 0.001) from
      that of pups born to control females, but mean litter size was smaller for
      females treated with cabergoline (P < or = 0.073) than for the control females.
      Although all cabergoline treatments in this study were ineffective at preventing
      reproduction in coyotes, progressive inhibition of prolactin and progesterone
      with increasing dosages of cabergoline indicates that higher doses might be
      effective in preventing reproduction in coyotes. However, the physiological
      differences from other canine species in dopamine D2 receptors and mechanisms of
      luteal support may ultimately prevent the use of cabergoline for reproductive
      control in coyotes.

PMID- 12220165
TI  - Ovarian function in the Nile hippopotamus and the effects of Depo-Provera
      administration.
AB  - The preliminary results of an investigation into the reproductive endocrinology
      of the hippopotamus (Hippopotamus amphibius) and the effects of the progestin
      Depo-Provera on ovarian function are presented. Faecal progestagen analysis
      indicated that hippos have an oestrous cycle of 29.2 +/- 0.9 days and faecal
      progestagen concentrations of 323.6 +/- 31.4 ng g(-1) during the luteal phase.
      Concentrations were higher (765.9 +/- 162.4 ng g(-1); P < 0.05) during pregnancy
      than during the luteal phase and remained high until parturition. A lactational
      anoestrus was usually, but not always, observed during nursing. The onset of
      puberty was observed in three animals and started at 2.5-3.5 years of age. After
      Depo-Provera treatment, increases in faecal progestagens indicative of ovulation
      were observed and were not significantly different from luteal concentrations
      observed before treatment (236.3 +/- 24.4 versus 340.1 +/- 47.9 ng g(-1),
      respectively); however, the duration of the luteal phase was shorter (P < 0.05)
      than before treatment (11.3 +/- 1.0 versus 18.9 +/- 1.0 days, respectively).
      Females returned to normal cyclicity at day 100.7 +/- 15.3 (range 70-116 days)
      after administration and one female conceived on day 100 after administration.

PMID- 12220166
TI  - Long-term fertility control in the kangaroo and the wallaby using levonorgestrel
      implants.
AB  - Non-lethal management techniques are needed for overabundant captive and wild
      populations of macropodid marsupials for which lethal techniques are considered
      inappropriate and may be hazardous. The tammar wallaby, Macropus eugenii, was
      used as a model species to investigate the effect of s.c. levonorgestrel implants
      on reproduction during breeding and non-breeding seasons. Implants were tested on
      captive and wild populations of eastern grey kangaroos, Macropus giganteus. In
      both species, levonorgestrel successfully stopped reproduction by inhibiting
      oestrus. However, levonorgestrel did not affect the reactivation and subsequent
      development of blastocysts in diapause that had been conceived before treatment
      and it did not impair lactation, as young were reared to weaning in both species.
      The contraceptive effects of the implant were reversible, as removal of the
      implants from tammar wallabies was followed by a rapid return of fertility.
      Levonorgestrel implants had no apparent adverse effects on body condition in
      either species, although in the wild kangaroos a small increase in body condition
      did occur. Levonorgestrel implants are long-acting and so far have provided 48
      months of contraception in the tammar wallaby and 27 months of contraception in
      the kangaroo, although the implants should provide contraception for more than 5
      years in the kangaroo. Thus, levonorgestrel implants provide a safe, highly
      effective and long-term method of fertility control for macropodid marsupials and
      should be applicable for the management of overabundant captive and selected wild
      populations.

PMID- 12220167
TI  - Risk assessment for release of genetically modified organisms: a virus to reduce
      the fertility of introduced wild mice, Mus domesticus.
AB  - Risk assessment is a key task in developing genetically modified organisms (GMOs)
      intended for release into the environment. A risk assessment protocol is
      described, focusing on genetically modified biological control agents intended to
      reduce fertility in mammalian pests. The protocol is being applied to development
      of an immunocontraceptive murine cytomegalovirus vaccine intended to reduce the
      frequency and extent of costly troublesome plagues of introduced house mice, Mus
      domesticus, in southern Australia. Success of the agent, including regulatory
      approval for release to target populations, will depend on demonstrated
      biosafety, on the biophysical consequences of releasing the agent, and on public
      perceptions of the consequences and ongoing risks. The proposed risk assessment
      protocol addresses biosafety and the biophysical and social risks. It elicits
      perceptions of interaction and risk from the project scientists and from
      representatives of interested or affected sectors of society. The perceptions are
      documented for examination interactively in subsequent socially inclusive formal
      risk assessments. Representatives of the relevant social sectors participate with
      the scientists, iteratively if needed, in a workshop to assess the risks of
      releasing the particular GMO into the environment, using a formal inductive
      procedure, GENHAZ, designed specifically for assessment and management of the
      risks of GMOs. Use of this protocol is intended to precede and complement risk
      assessment and risk management procedures specified by gene technology
      legislation and regulations.

PMID- 12220168
TI  - Dependence of population response to fertility control on the survival of sterile
      animals and their role in regulation.
AB  - The species for which fertility control is presently used, or for which it is
      being developed, range from small mammal pests, such as the house mouse (Mus
      domesticus), to large mammals, such as the African elephant (Loxodonta africana).
      However, the possibility of a population response other than a reduction in
      abundance proportional to the fraction of animals rendered infertile has been
      shown in field trials. For example, when intermediate levels of sterility were
      imposed on wild populations of European rabbits (Oryctolagus cuniculus), there
      was an increase in their abundance, on an annual basis, due to enhanced survival
      of juveniles and adult females. In this article, we relate intraspecific
      regulatory processes to the response of populations to fertility control using a
      set of density-dependent structured-population models. In each of the models, the
      population is exposed periodically to a fertility control agent that renders a
      fraction of fertile females sterile. Although our intention is not to predict the
      population response of any one particular species, the results of the models are
      illustrated using parameter values that are representative of populations of the
      European fox (Vulpes vulpes) in south-eastern Australia. When populations were
      regulated by density-dependent mechanisms in which sterile females did not
      participate, such as competition for resources among young animals or competition
      among fertile females for breeding sites or territories, then populations could
      increase in abundance for low and intermediate levels of imposed sterility. For
      other intraspecific regulatory mechanisms, such as competition for resources
      between all individuals, all levels of sterility were observed to reduce
      abundance. The population response was sensitive to (i) whether the survival of
      sterile adults was higher than that of fertile adults, (ii) whether animals could
      be sterilized before sexual maturity, and (iii) whether density dependence was
      modelled as a threshold process.

PMID- 12220169
TI  - Molecular approaches for the evaluation of immune responses to zona pellucida
      (ZP) and development of second-generation ZP vaccines.
AB  - It has long been established that there are major variations in both the
      immunogenicity and antigenicity of native zona pellucida (ZP) proteins. These
      differences appear to be more pronounced with respect to genetically engineered
      ZP proteins, which do not have native post-translational modifications (for
      example glycosylation and sulphation). As the number of animal species that are
      now included in population management programmes using native porcine zona
      pellucida (PZP) proteins expands, it is increasingly important to carry out
      studies to evaluate the immune response variations among different species as
      well as the individual variation within a species. In an attempt to compare these
      complex immune responses, we have evaluated antibodies from numerous species
      immunized with native, genetically engineered ZP and synthetic ZP peptides. Such
      an immunocontraceptive method could have great potential. These studies are
      critical not only for the development of predictable immune responses that result
      in permanent sterilization versus reversible contraceptive effects, but also for
      predicting which vaccinogens (native ZP protein versus genetically engineered ZP
      proteins) might have detrimental effects on animal and human populations.

PMID- 12220170
TI  - Processing of von Willebrand factor by ADAMTS-13.

PMID- 12220171
TI  - Structure of a nitric oxide synthase heme protein from Bacillus subtilis.
AB  - Eukaryotic nitric oxide synthases (NOSs) produce nitric oxide to mediate
      intercellular signaling and protect against pathogens. Recently, proteins
      homologous to mammalian NOS oxygenase domains have been found in prokaryotes and
      one from Bacillus subtilis (bsNOS) has been demonstrated to produce nitric oxide
      [Adak, S., Aulak, K. S., and Stuehr, D. J. (2002) J. Biol. Chem. 277, 16167
      16171]. We present structures of bsNOS complexed with the active cofactor
      tetrahydrofolate and the substrate L-arginine (L-Arg) or the intermediate
      N(omega)-hydroxy-L-arginine (NHA) to 1.9 or 2.2 A resolution, respectively. The
      bsNOS structure is similar to those of the mammalian NOS oxygenase domains
      (mNOS(ox)) except for the absence of an N-terminal beta-hairpin hook and zinc
      binding region that interact with pterin and stabilize the mNOS(ox) dimer.
      Changes in patterns of residue conservation between bacterial and mammalian NOSs
      correlate to different binding modes for pterin side chains. Residue conservation
      on a surface patch surrounding an exposed heme edge indicates a likely
      interaction site for reductase proteins in all NOSs. The heme pockets of bsNOS
      and mNOS(ox) recognize L-Arg and NHA similarly, although a change from Val to Ile
      beside the substrate guanidinium may explain the 10-20-fold slower dissociation
      of product NO from the bacterial enzyme. Overall, these structures suggest that
      bsNOS functions naturally to produce nitrogen oxides from L-Arg and NHA in a
      pterin-dependent manner, but that the regulation and purpose of NO production by
      NOS may be quite different in B. subtilis than in mammals.

PMID- 12220172
TI  - Increased A beta peptides and reduced cholesterol and myelin proteins
      characterize white matter degeneration in Alzheimer's disease.
AB  - Relative to the gray matter, there is a paucity of information regarding white
      matter biochemical alterations and their contribution to Alzheimer's disease
      (AD). Biochemical analyses of AD white matter combining size-exclusion, normal
      phase, and gas chromatography, immunoassays, and Western blotting revealed
      increased quantities of Abeta40 and Abeta42 in AD white matter accompanied by
      significant decreases in the amounts of myelin basic protein, myelin proteolipid
      protein, and 2',3'-cyclic nucleotide 3'-phosphodiesterase. In addition, the AD
      white matter cholesterol levels were significantly decreased while total fatty
      acid content was increased. In some instances, these white matter biochemical
      alterations were correlated with patient apolipoprotein E genotype, Braak stage,
      and gender. Our observations suggest that extensive white matter axonal
      demyelination underlies Alzheimer's pathology, resulting in loss of capacitance
      and serious disturbances in nerve conduction, severely damaging brain function.
      These white matter alterations undoubtedly contribute to AD pathogenesis and may
      represent the combined effects of neuronal degeneration, microgliosis,
      oligodendrocyte injury, microcirculatory disease, and interstitial fluid stasis.
      To accurately assess the success of future therapeutic interventions, it is
      necessary to have a complete appreciation of the full scope and extent of AD
      pathology.

PMID- 12220173
TI  - Binding of discoidin domain receptor 2 to collagen I: an atomic force microscopy
      investigation.
AB  - Collagens have recently been identified as ligands for discoidin domain receptors
      (DDR1 and DDR2), generating an interest in studying the properties of binding of
      DDR to its ligand. We are interested in the interaction of DDR2 with collagen I
      because of its potential role in liver fibrosis. Our in vitro binding assay
      utilizes DDR2-Fc fusion proteins, which can be clustered (multimerized) by use of
      antibodies to form DDR2 complexes. Binding of DDR2 complexes to collagen I coated
      on plastic plates was established by a microplate-based assay using Eu(3+)
      labeled proteins and time-resolved fluorometry. Clustering of the DDR2-Fc with
      antibody was found to be requisite for binding to collagen in vitro. Using atomic
      force microscopy (AFM) in an aqueous environment, we characterized the surface
      topographies of DDR2 complexes and collagen I, and investigated binding of this
      receptor-ligand pair. We were able to image and identify binding of DDR2
      complexes onto individual molecules of triple-helical collagen and provide
      insight into the number and locations of binding sites on collagen I. In most
      cases, a single receptor complex bound to a single collagen molecule and there
      were preferred DDR2 binding sites on the collagen I triple helix. These data were
      validated by rotary-replication transmission electron microscopy (TEM) of
      glycerol-sprayed samples.

PMID- 12220174
TI  - The [Lys(-2)-Arg(-1)-des(17-21)]-endothelin-1 peptide retains the specific Arg(
      1)-Asp8 salt bridge but reveals discrepancies between NMR data and molecular
      dynamics simulations.
AB  - The [des(17-21)]-endothelin-1 (CSH-ET) and [Lys(-)(2)-Arg(-)(1)-des(17-21)]
      endothelin-1 (KR-CSH-ET) peptides, designed by removing the five-residue
      hydrophobic tail from the endothelin-1 (ET-1) and [Lys(-)(2)-Arg(-)(1)]
      endothelin-1 (KR-ET-1) peptides, respectively, were synthesized. Previous studies
      on KR-ET-1 showed that, in contrast to ET-1, this engineered compound displays a
      pH-dependent conformational change related to the formation of a stabilizing salt
      bridge between the Arg(-)(1) and Asp(8) side chains. CD and NMR spectra indicate
      that CSH-ET and KR-CSH-ET display conformational behavior similar to those of ET
      1 and KR-ET-1, respectively. The short salt bridge-stabilized KR-CSH-ET peptide
      therefore appears to be an attractive elementary scaffold for drug design. The
      solution structure of the salt-bridged form of KR-CSH-ET was determined by NMR at
      pH 4.5 and is very similar to the corresponding form of the parent KR-ET-1
      peptide. Molecular dynamics simulations of the salt-bridged form of KR-CSH-ET
      were performed using both the GB/SA implicit solvation scheme or an explicit
      solvation and the particle-mesh Ewald method for long-range electrostatic
      calculation. Unexpectedly, the Arg(-)(1)-Asp(8) salt bridge does not display in
      the simulation the stability that could be expected from the experimental data.
      The cooperative involvement of a cation-pi interaction in formation of the salt
      bridge has been hypothesized. Difficulties in accurately simulating cation-pi
      interactions might be responsible for the lack of stability in the simulation. At
      this time, however, no definitive explanation for the observed discrepancy
      between experiments and simulations is available, and further experimental
      studies appear to be necessary to fully understand in atomic detail the pH
      dependent conformational change observed in the KR-ET-1 series.

PMID- 12220175
TI  - YjeQ, an essential, conserved, uncharacterized protein from Escherichia coli, is
      an unusual GTPase with circularly permuted G-motifs and marked burst kinetics.
AB  - The Escherichia coli protein YjeQ represents a protein family whose members are
      broadly conserved in bacteria and have been shown to be indispensable to the
      growth of E. coli and Bacillus subtilis [Arigoni, F., et al. (1998) Nat.
      Biotechnol. 16, 851]. Proteins of the YjeQ family contain all sequence motifs
      typical of the vast class of P-loop-containing GTPases, but show a circular
      permutation, with a G4-G1-G3 pattern of motifs as opposed to the regular G1-G3-G4
      pattern seen in most GTPases. All YjeQ family proteins display a unique domain
      architecture, which includes a predicted N-terminal OB-fold RNA-binding domain,
      the central permuted GTPase module, and a zinc knuckle-like C-terminal cysteine
      cluster. This domain architecture suggests a possible role for YjeQ as a
      regulator of translation. YjeQ was overexpressed, purified to homogeneity, and
      shown to contain 0.6 equiv of GDP. Steady state kinetic analyses indicated slow
      GTP hydrolysis, with a k(cat) of 9.4 h(-)(1) and a K(m) for GTP of 120 microM
      (k(cat)/K(m) = 21.7 M(-)(1) s(-)(1)). YjeQ also hydrolyzed other nucleoside
      triphosphates and deoxynucleotide triphosphates such as ATP, ITP, and CTP with
      specificity constants (k(cat)/K(m)) ranging from 0.2 to 1.0 M(-)(1) s(-)(1). Pre
      steady state kinetic analysis of YjeQ revealed a burst of nucleotide hydrolysis
      for GTP described by a first-order rate constant of 100 s(-)(1) as compared to a
      burst rate of 0.2 s(-)(1) for ATP. In addition, a variant in the G1 motif of YjeQ
      (S221A) was substantially impaired for GTP hydrolysis (0.3 s(-)(1)) with a less
      significant impact on the steady state rate (1.8 h(-)(1)). In summary, E. coli
      YjeQ is an unusual, circularly permuted P-loop-containing GTPase, which catalyzes
      GTP hydrolysis at a rate 45 000 times greater than that of turnover.

PMID- 12220176
TI  - Enhanced strand invasion by peptide nucleic acid-peptide conjugates.
AB  - Efficient and selective recognition of DNA by proteins is due to sequence
      specific interactions with a target site and nonselective electrostatic
      interactions that promote the target's rapid location. If synthetic molecules
      could mimic these functions, they would render a wide range of chromosome
      sequences accessible to rationally designed probes. Here we describe conjugates
      between bispeptide nucleic acids (bisPNAs) designed to specifically recognize
      duplex DNA and peptides that have been designed to promote rapid sequence
      recognition. Peptide design was based on the surface of staphylococcal nuclease,
      a cationic DNA binding protein with low sequence selectivity. We observe that
      attachment of the designed peptide increases rates of strand invasion by 100-fold
      relative to unmodified bisPNA. The peptide can contain D-amino acids, increasing
      the likelihood that it will be stable in cell extract and inside cells. Binding
      of the conjugate containing the D-amino acid peptide occurred over a broad range
      of experimental conditions and was sensitive to a single mismatch. Strand
      invasion was efficient at neutral to basic pH, a wide range of temperatures (0-65
      degrees C), and in the presence of up to 7 mM Mg(2+) and 100 mM Na(+) or K(+).
      Our data suggest that attachment of peptides that mimic cationic protein surfaces
      to PNAs can afford conjugates that mimic the rapid and selective binding that
      characterizes native DNA binding proteins. Rapid strand invasion over a wide
      range of experimental conditions should further expand the utility of strand
      invasion by PNAs.

PMID- 12220177
TI  - Purification and characterization of two polymorphic variants of short chain acyl
      CoA dehydrogenase reveal reduction of catalytic activity and stability of the
      Gly185Ser enzyme.
AB  - Short chain acyl-CoA dehydrogenase (SCAD) is a homotetrameric flavoenzyme that
      catalyzes the first intramitochondrial step in the beta-oxidation of fatty acids.
      Two polymorphisms in the coding region of the SCAD gene, 511C>T (R147W) and
      625G>A (G185S), have been shown to be associated with an increased level of
      ethylmalonic acid excretion in urine, a clinical characteristic of SCAD
      deficiency. To characterize the biochemical consequences of these variations, in
      vitro site-directed mutagenesis and prokaryotic expression were used to produce
      the corresponding SCAD variant proteins. Both variant proteins were unstable when
      produced in Escherichia coli, but could be rescued and subsequently purified by
      coexpressing them with the bacterial chaperonin GroEL/ES. The k(cat)/K(m) values
      of the green wild-type, R147W, and G185S SCAD enzymes coexpressed with GroEL/ES
      were 33, 30, and 10 microM(-)(1) s(-)(1), respectively. There were minimal
      differences in the kinetic parameters measured for the green, degreened, and wild
      type enzymes coexpressed with GroEL/ES, and the R147W variant when butyryl-CoA
      was used as a substrate. The catalytic efficiency of the G185S variant enzyme,
      however, was reduced compared to that of the wild-type enzyme. The thermal and
      guanidine HCl stability of the purified enzymes as determined by fluorescence,
      far-UV CD spectroscopy, and incubation-induced rest activity showed the following
      order of relative stability: wild-type enzyme > R147W > G185S. Near-UV CD
      spectroscopy indicated that these impairments are caused by decreased flexibility
      in the tertiary conformation of the two mutant enzymes. The common SCAD
      polymorphisms may lead to clinically relevant alterations in enzyme function.

PMID- 12220178
TI  - Crystal structure of the cellulase Cel9M enlightens structure/function
      relationships of the variable catalytic modules in glycoside hydrolases.
AB  - Cellulases cleave the beta-1.4 glycosidic bond of cellulose. They have been
      characterized as endo or exo and processive or nonprocessive cellulases according
      to their action mode on the substrate. Different types of these cellulases may
      coexist in the same glycoside hydrolase family, which have been classified
      according to their sequence homology and catalytic mechanism. The bacterium C.
      celluloyticum produces a set of different cellulases who belong mostly to
      glycoside hydrolase families 5 and 9. As an adaptation of the organism to
      different macroscopic substrates organizations and to maximize its cooperative
      digestion, it is expected that cellulases of these families are active on the
      various macroscopic organizations of cellulose chains. The nonprocessive
      cellulase Cel9M is the shortest variant of family 9 cellulases (subgroup 9(C))
      which contains only the catalytic module to interact with the substrate. The
      crystal structures of free native Cel9M and its complex with cellobiose have been
      solved to 1.8 and 2.0 A resolution, respectively. Other structurally known family
      9 cellulases are the nonprocessive endo-cellulase Cel9D from C. thermocellum and
      the processive endo-cellulase Cel9A from T. fusca, from subgroups 9(B1) and 9(A),
      respectively, whose catalytic modules are fused to a second domain. These enzymes
      differ in their activity on substrates with specific macroscopic appearances. The
      comparison of the catalytic module of Cel9M with the two other known GH family 9
      structures may give clues to explain its substrate profile and action mode.

PMID- 12220179
TI  - Relaxation, equilibrium oligomerization, and molecular symmetry of the VASP (336
      380) EVH2 tetramer.
AB  - An investigation of the structural and dynamic properties of the C-terminal
      fragment of the human protein VASP (VASP 336-380) has been performed. Full length
      VASP has been shown to be tetrameric in solution, and the C-terminal 45 residues
      of the protein have been suggested to be responsible for the oligomerization. We
      have expressed and purified a C-terminal fragment of the human VASP protein from
      residue 336-380. It was found to form a stable domain in its own right. The
      fragment was shown by CD spectroscopy to form a helical structure, stable under a
      wide range of temperature and pH conditions. A (15)N-HSQC-experiment exhibits
      only one set of peaks, suggesting a high degree of symmetry for a putative
      oligomer. Measurements of the rotational correlation time tau(C) of the molecule
      and analytical ultracentrifugation data show VASP (336-380) to be entirely
      tetrameric in solution. The secondary structure was confirmed from a (15)N-NOESY
      HSQC experiment and is completely alpha-helical. We conclude that VASP (336-380)
      forms a tetramer in solution via a coiled coil arrangement and is solely
      responsible for tetramerization of full-length VASP.

PMID- 12220180
TI  - Kinetic, Raman, NMR, and site-directed mutagenesis studies of the Pseudomonas sp.
      strain CBS3 4-hydroxybenzoyl-CoA thioesterase active site.
AB  - 4-Hydroxybenzoyl-coenzyme A (4-HBA-CoA) thioesterase catalyzes the hydrolysis of
      4-HBA-CoA to 4-hydroxybenzoate and CoA. X-ray crystallographic analysis of the
      liganded enzyme has shown that the benzoyl thioester and pantetheine moieties of
      the substrate ligand are bound in a narrow crevice while the nucleotide moiety
      rests on the protein surface (Thoden, J. B., Holden, H. M., Zhuang, Z. and
      Dunaway-Mariano, D. (2002) X-ray Crystallographic Analyses of Inhibitor and
      Substrate Complexes of Wild-type and Mutant 4-Hydroxybenzoyl-CoA Thioesterase, J.
      Biol. Chem., in press). Asp17 is positioned in the crevice, close to the
      substrate thioester C=O, which in turn interacts with the positive pole of an
      alpha-helix macrodipole. In this paper we report the results from spectral,
      mutagenesis, and kinetic studies which show (1) that substrate activation
      involves restricted thioester C=O conformational freedom and a modest enhancement
      of C=O bond polarization, (2) that the nucleotide unit of the substrate is bound
      through interaction with the protein surface, and (3) that Asp17 contributes a
      rate factor of 10(4), consistent with its proposed role of general base or
      nucleophile.

PMID- 12220181
TI  - Role for phospholipid interactions in the trafficking defect of Delta F508-CFTR.
AB  - Cystic fibrosis commonly occurs as a consequence of the DeltaF508 mutation in the
      first nucleotide binding fold domain (NBF-1) of CFTR. The mutation causes
      retention of the mutant CFTR molecule in the endoplasmic reticulum, and this
      aberrant trafficking event is believed to be due to defective interactions
      between the mutant NBF-1 domain and other cellular factors in the endoplasmic
      reticulum. Since the NBF-1 domain has been shown to interact with membranes, we
      wanted to investigate whether NBF-1 and CFTR interactions with specific
      phospholipid chaperones might play a role in trafficking. We have found that the
      recombinant wild-type NBF-1 interacts selectively with phosphatidylserine (PS)
      rather than phosphatidylcholine (PC). By contrast, NBF-1 carrying the DeltaF508
      mutation loses the ability to discriminate between these two phospholipids. In
      cells expressing DeltaF508-CFTR, replacement of PC by noncharged analogues
      results in an absolute increase in CFTR expression. In addition, we detected
      progressive expression of higher molecular weight CFTR forms. Thus, phospholipid
      chaperones may be important for CFTR trafficking, and contribute to the pathology
      of cystic fibrosis.

PMID- 12220182
TI  - Probing the Tetrahymena group I ribozyme reaction in both directions.
AB  - The Tetrahymena L-21 ScaI ribozyme derived from the self-splicing group I intron
      catalyzes a reversible reaction analogous to the first step of self-splicing:
      CCCUCUA (S) + [UC]G right harpoon over left harpoon CCCUCU (P) + [UC]GA. To
      relate our understanding of the ribozyme to the self-splicing reaction and to
      further the mechanistic dissection of the ribozyme reaction, we have established
      a quantitative kinetic and thermodynamic framework for the forward and reverse
      reaction of the L-21 ScaI ribozyme under identical conditions. Examination of the
      framework shows that binding of products is cooperative with binding enhanced 5
      fold, as was observed previously for binding of the substrates. Further, binding
      of UCGA is 12-fold weaker than binding of the unphosphorylated UCG, analogous to
      the 20-fold weaker binding of phosphorylated S relative to P; the molecular
      interactions underlying the stronger binding of UCG were traced to the 3'
      hydroxyl group of UCG. The symmetrical effects on binding of substrates and
      products result in the equilibrium between ribozyme-bound species, K(int), that
      is essentially unperturbed from the solution equilibrium, K(ext) (K(int) =
      [E.P.UCGA]/[E.S.UCG] = 4.6 and K(ext) = [P][UCGA]/[S][UCG] = 1.9). Last, we show
      that the pK(a) values of the nucleophiles in the forward and reverse reactions
      are >/=10. This observation suggests that metal ion activation of the nucleophile
      and stabilization of the leaving group can only account for a portion of the rate
      enhancement of this ribozyme. These and prior results suggest that the
      Tetrahymena group I ribozyme, analogous to protein enzymes, uses multiple
      catalytic strategies to achieve its large rate enhancement.

PMID- 12220183
TI  - Ferrous ion binding to recombinant human H-chain ferritin. An isothermal
      titration calorimetry study.
AB  - Iron deposition within the iron storage protein ferritin involves a complex
      series of events consisting of Fe(2+) binding, transport, and oxidation at
      ferroxidase sites and mineralization of a hydrous ferric oxide core, the storage
      form of iron. In the present study, we have examined the thermodynamic properties
      of Fe(2+) binding to recombinant human H-chain apoferritin (HuHF) by isothermal
      titration calorimetry (ITC) in order to determine the location of the primary
      ferrous ion binding sites on the protein and the principal pathways by which the
      Fe(2+) travels to the dinuclear ferroxidase center prior to its oxidation to
      Fe(3+). Calorimetric titrations show that the ferroxidase center is the principal
      locus for Fe(2+) binding with weaker binding sites elsewhere on the protein and
      that one site of the ferroxidase center, likely the His65 containing A-site,
      preferentially binds Fe(2+). That only one site of the ferroxidase center is
      occupied by Fe(2+) implies that Fe(2+) oxidation to form diFe(III) species might
      occur in a stepwise fashion. In dilute anaerobic protein solution (3-5 microM),
      only 12 Fe(2+)/protein bind at pH 6.51 increasing to 24 Fe(2+)/protein at pH 7.04
      and 7.5. Mutation of ferroxidase center residues (E62K+H65G) eliminates the
      binding of Fe(2+) to the center, a result confirming the importance of one or
      both Glu62 and His65 residues in Fe(2+) binding. The total Fe(2+) binding
      capacity of the protein is reduced in the 3-fold hydrophilic channel variant S14
      (D131I+E134F), indicating that the primary avenue by which Fe(2+) gains access to
      the interior of ferritin is through these eight channels. The binding
      stoichiometry of the channel variant is one-third that of the recombinant wild
      type H-chain ferritin whereas the enthalpy and association constant for Fe(2+)
      binding are similar for the two with an average values (DeltaH degrees = 7.82
      kJ/mol, binding constant K = 1.48 x 10(5) M(-)(1) at pH 7.04). Since channel
      mutations do not completely prevent Fe(2+) binding to the ferroxidase center,
      iron gains access to the center in approximately one-third of the channel variant
      molecules by other pathways.

PMID- 12220184
TI  - The stable assembly of newly synthesized PsaE into the photosystem I complex
      occurring via the exchange mechanism is facilitated by electrostatic
      interactions.
AB  - Photosystem I (PSI) is a photochemically active membrane protein complex that
      functions at the reducing site of the photosynthetic electron-transfer chain as
      plastocyanin-ferredoxin oxidoreductase. PsaE, a peripheral subunit of the PSI
      complex, plays an important role in the function of PSI. PsaE is involved in the
      docking of ferredoxin/flavodoxin to the PSI complex and also participates in the
      cyclic electron transfer around PSI. The molecular characterization of the
      assembly of newly synthesized PsaE in the thylakoid membranes or in isolated PSI
      complexes is the subject of the present study. For this purpose the Mastigocladus
      laminosus psaE gene was cloned and overexpressed in Escherichia coli, and the
      resulting PsaE protein was purified to homogeneity by affinity chromatography.
      The purified PsaE was then introduced into thylakoids isolated from M. laminosus,
      and the newly introduced PsaE subunit saturates the membrane. The solubilization
      and separation of the different thylakoid protein complexes indicated that PsaE
      accumulates specifically in its functional location, the PSI complex. A similar
      stable assembly was detected when PsaE was introduced into purified PSI
      complexes, i.e., in the absence of other thylakoid components. This strongly
      indicates that the information for the stable assembly of PsaE into PSI lies
      within the polypeptide itself and within other subunits of the PSI complex that
      interact with it. To determine the nature of these interactions, the assembly
      reaction was performed in conditions affecting the ionic/osmotic strength. We
      found that altering the ionic strength significantly affects the capability of
      PsaE to assemble into isolated thylakoids or PSI complexes, strongly supporting
      the fact that electrostatic interactions are formed between PsaE and other PSI
      subunits. Moreover, the data suggest that the formation of electrostatic
      interactions occurs concomitantly with an exchange step in which newly introduced
      PsaE replaces the subunit present in situ.

PMID- 12220185
TI  - The two histidine axial ligands of the primary electron donor chlorophylls (P700)
      in photosystem I are similarly perturbed upon P700+ formation.
AB  - The extent of delocalization of the positive charge in the oxidized dimer of
      chlorophyll (Chl) constituting P700, the primary electron donor of photosystem I
      (PSI), has been investigated by analyzing the perturbation upon P700(+) formation
      of infrared (IR) vibrational modes of the two His axial ligands of the two P700
      Chl molecules. Fourier transform IR (FTIR) difference spectra of the
      photooxidation of P700 in PSI core complexes isolated from Synechocystis sp. PCC
      6803 isotopically labeled either globally with (15)N or more specifically with
      (13)C on all the His residues reveal isotopic shifts of a differential signal at
      1102/1108 cm(-)(1). This signal is assigned to a downshift upon P700(+) formation
      of the predominantly C(5)-Ntau imidazole stretching mode of His residue(s). The
      amplitude of this signal is reduced by approximately half in FTIR spectra of
      Synechocystis mutants in which His PsaB 651, the axial ligand to one of the two
      Chl molecules in P700, is replaced by Cys, Gln, or Leu. These observations
      provide further evidence that the positive charge in P700(+) is essentially
      delocalized over the two Chl molecules, in agreement with a previous FTIR study
      in which the frequency of the vibrational modes of the 9-keto and 10a-ester C=O
      groups of the two Chl's in P700, P700(+), and (3)P700 were firmly established for
      the first time [Breton, J., et al. (1999) Biochemistry 38, 11585-11592]. Only
      limited perturbations of the amplitude and frequency of the 9-keto and 10a-ester
      C=O bands of the P700 Chl are elicited by the mutations. On the basis of
      comparable mutational studies of the primary electron donor in purple bacteria,
      these perturbations are attributed to small molecular rearrangements of the Chl
      macrocycle and substituents caused by the repositioning of the P700 dimer in the
      new protein cavity generated by the mutations. It is proposed that the
      perturbation of the FTIR spectra upon mutation of a His axial ligand of the P700
      Chl recently reported in Chlamydomonas reinhardtii [Hastings, G., et al. (2001)
      Biochemistry 40, 12943-12949] can be explained by the same effect without the
      need for a new assignment of the C=O bands of P700. The distribution of
      charge/spin in P700(+) and (3)P700 determined by FTIR spectroscopy is discussed
      in relation with the contrasting interpretations derived from recent magnetic
      resonance experiments.

PMID- 12220186
TI  - Mutational analyses of the photosynthetic reaction center-bound triheme
      cytochrome subunit and cytochrome c2 in the purple bacterium Rhodovulum
      sulfidophilum.
AB  - The purple photosynthetic bacterium Rhodovulum sulfidophilum has an unusual
      reaction center- (RC-) bound cytochrome subunit with only three hemes, although
      the subunits of other purple bacteria have four hemes. To understand the electron
      transfer pathway through this subunit, three mutants of R. sulfidophilum were
      constructed and characterized: one lacking the RC-bound cytochrome subunit,
      another one lacking cytochrome c(2), and another one lacking both of these. The
      mutant lacking the RC-bound cytochrome subunit was grown photosynthetically with
      about half the growth rate of the wild type, indicating that the presence of the
      cytochrome subunit, while not indispensable, is still advantageous for the
      photosynthetic electron transfer to support its growth. The mutant lacking both
      the cytochrome subunit and cytochrome c(2) showed a slower rate of growth by
      photosynthesis (about a fourth of that of the wild type), indicating that
      cytochrome c(2) is the dominant electron donor to the RC mutationally devoid of
      the cytochrome subunit. On the other hand, the mutant lacking only the cytochrome
      c(2) gene grew photosynthetically as fast as the wild type, indicating that
      cytochrome c(2) is not the predominant donor to the RC-bound triheme cytochrome
      subunit. We further show that newly isolated soluble cytochrome c-549 with a
      redox midpoint potential of +238 mV reduced the photooxidized cytochrome subunit
      in vitro, suggesting that c-549 mediates the cytochrome c(2)-independent electron
      transfer from the bc(1) complex to the RC-bound cytochrome subunit. These results
      indicate that the soluble components donating electrons to the RC-bound triheme
      cytochrome subunit are somewhat different from those of other purple bacteria.

PMID- 12220187
TI  - RNA methyltransferases utilize two cysteine residues in the formation of 5
      methylcytosine.
AB  - Proteins that have sequence homology with known RNA m(5)C methyltransferases
      contain two conserved cysteines, each of which lies within a sequence that bears
      similarity to a methyltransferase active site. Other enzymes that transfer a
      methyl group to carbon 5 of a pyrimidine nucleotide, such as the bacterial DNA
      m(5)C methyltransferases, utilize their single conserved cysteine residue to form
      a covalent Michael adduct with carbon 6 of the pyrimidine ring during catalysis.
      We present a model for the utilization of two cysteines in catalysis by RNA m(5)C
      methyltransferases. It is proposed that one thiol acts in a classical fashion by
      forming a covalent link to carbon 6 of the pyrimidine base, while the other
      cysteine assists breakdown of the covalent adduct. Therefore, alteration of the
      assisting cysteine is anticipated to stabilize the covalent enzyme-RNA
      intermediate. The model was conceived as a possible explanation for the effects
      of mutations that change the conserved cysteines in Nop2p, an apparent RNA m(5)C
      methyltransferase that is essential for ribosome assembly and yeast viability.
      Evidence for the predicted accumulation of protein-RNA complexes following
      mutation of the assisting cysteine has been obtained with Nop2p and a known tRNA
      m(5)C methyltransferase called Ncl1p (Trm4).

PMID- 12220188
TI  - Use of 2-aminopurine and tryptophan fluorescence as probes in kinetic analyses of
      DNA polymerase beta.
AB  - Although the use of 2-aminopurine (2-AP) as a probe in stopped-flow analyses of
      DNA polymerase beta (Pol beta) had provided important mechanistic insight, the
      conditions used were limited by the location of 2-AP and the use of a combination
      of tryptophan (Trp) and 2-AP fluorescence. This study examined different DNA
      substrates to identify several factors that can affect the observed signal in
      stopped-flow experiments. Both Trp and 2-AP emissions were separately excited and
      monitored. It was found that both probes show a fast phase and a slow phase of
      fluorescence changes, but the direction and the amplitude vary greatly between
      the two probes and between different DNA substrates. Detailed analyses suggested
      that the location of 2-AP in the template has a significant impact on the
      fluorescence properties of 2-AP and that a location opposite the incoming dNTP,
      which has been used in all such studies in the past, is not optimal. In
      particular, the results show that placing 2-AP one base after the templating base
      greatly enhances the signal intensity, which suggests a significant change in
      base stacking interactions at this position during nucleotide incorporation.
      These results allowed us to derive an improved set of conditions which were then
      used to reevaluate results from previous reports. It also allows greater freedom
      in the type of base pairs studied, since 2-AP is not the templating base in the
      nascent base pair. Kinetic constants were determined for dNTP and catalytic
      Mg(2+). The results obtained from stopped-flow experiments were compared to
      results from chemical quench. Stopped flow of incorrect dNTP incorporation and
      the reverse reaction are also reported, which provide useful information to the
      mechanism of Pol beta.

PMID- 12220189
TI  - Mutational analysis of the base-flipping mechanism of uracil DNA glycosylase.
AB  - The DNA repair enzyme uracil DNA glycosylase (UDG) locates unwanted uracil bases
      in genomic DNA using a remarkable base-flipping mechanism in which the entire
      deoxyuridine nucleotide is rotated from the DNA base stack into the enzyme active
      site. Enzymatic base flipping has been described as a three-step process
      involving phosphodiester backbone pinching, base extrusion through active pushing
      and plugging by a leucine side chain that inserts in the DNA minor groove, and,
      finally, pulling by hydrogen-bonding groups that interact with the extrahelical
      base. Here we employ mutagenesis in combination with transient kinetic approaches
      to assess the functional roles of six conserved enzymatic groups of UDG that have
      been implicated in the "pinch, push, plug, and pull" base-flipping mechanism. Our
      results show that these mutant enzymes are capable of flipping the uracil base
      from the duplex, but that many of these mutations prevent a subsequent induced
      fit conformational step in which catalytic groups of UDG dock with the flipped
      out base. These studies support our previous model for base flipping in which a
      conformational gating step closely follows base extrusion from the DNA duplex
      [Stivers, J. T., et al. (1999) Biochemistry 38, 952-963]. A model that accounts
      for the temporal and functional roles of these side chain interactions along the
      reaction pathway for base flipping is presented.

PMID- 12220190
TI  - Base-flipping mutations of uracil DNA glycosylase: substrate rescue using a
      pyrene nucleotide wedge.
AB  - We recently introduced a new substrate rescue tool for investigating enzymatic
      base flipping by uracil DNA glycosylase (UDG) in which a bulky pyrene nucleotide
      wedge (Y) was placed opposite a uracil in duplex DNA (i.e., a U/Y pair), thereby
      preorganizing the target base in an extrahelical conformation [Jiang, Y. L., et
      al. (2001) J. Biol. Chem. 276, 42347-54]. The pyrene wedge completely rescued the
      large catalytic defects resulting from removal of the natural Leu191 wedge,
      presumably mimicking the pushing and plugging function of this group. Here we
      employ the pyrene rescue method in combination with transient kinetic approaches
      to assess the functional roles of six conserved enzymatic groups of UDG that have
      been implicated in the "pinch, push, plug, and pull" base-flipping mechanism (see
      the preceding paper in this issue). We find that a U/Y base pair increases the
      apparent second-order rate constant for damaged site recognition by L191G pushing
      mutation by 45-fold as compared to a U/A pair, thereby fully rescuing the kinetic
      effects of the mutation. Remarkably, the U/Y pair also allows L191G to proceed
      through the conformational docking step that is severely comprised with the
      normal U/A substrate, and allows the active site of UDG to clamp around the
      extrahelical base. Thus, pyrene also fulfills the plugging role of the Leu191
      side chain. Preorganization of uracil in an extrahelical conformation by pyrene
      allows diffusion-controlled damage recognition by all of these base-flipping
      mutants, and allows the UDG conformational change to proceed as rapidly as the
      rate of uracil flipping with the natural U/A base pair. Thus, the pyrene wedge
      substrate allows UDG to recognize uracil by a lock-and-key mechanism, rather than
      the natural induced-fit mechanism. Unnatural pyrene base pairs may provide a
      general strategy to promote site-specific targeting of other enzymes that
      recognize extrahelical bases.

PMID- 12220191
TI  - Interaction between the C8 alpha-gamma and C8 beta subunits of human complement
      C8: role of the C8 beta N-terminal thrombospondin type 1 module and membrane
      attack complex/perforin domain.
AB  - Human C8 is one of five complement components (C5b, C6, C7, C8, and C9) that
      interact to form the cytolytic membrane attack complex (MAC). It is an oligomeric
      protein composed of a disulfide-linked C8alpha-gamma heterodimer and a
      noncovalently associated C8beta chain. C8alpha and C8beta are homologous; both
      contain an N-terminal thrombospondin type 1 (TSP1) module, a low-density
      lipoprotein receptor class A (LDLRA) module, an extended central segment referred
      to as the membrane attack/perforin (MACPF) domain, an epidermal growth factor
      (EGF) module, and a second TSP1 module at the C-terminus. In this study, the
      segment of C8beta that confers binding specificity toward C8alpha-gamma was
      identified using recombinant C8beta constructs in which the N- and/or C-terminal
      modules were deleted or exchanged with those from C8alpha. Constructs were tested
      for their ability to bind C8alpha-gamma in solution and express C8 hemolytic
      activity. Binding to C8alpha-gamma was found to be dependent on the TSP1 + LDLRA
      + MACPF segment of C8beta. Within this segment, the TSP1 module and MACPF domain
      are principally involved and act cooperatively to mediate binding. Results from
      activity assays suggest that residues within this segment also mediate binding
      and incorporation of C8 into the MAC.

PMID- 12220192
TI  - Affinity of Stat2 for the subunits of the interferon alpha receptor.
AB  - The interferon alpha receptor is composed of two subunits: IFNaR1 and IFNaR2.
      Interferon alpha binding to the receptor induces phosphorylation of tyrosine 466
      on IFNaR1, which in turn binds the SH2 domain of the latent transcription factor
      Stat2 to initiate signaling. Stat2 also binds to IFNaR2 in a constitutive,
      phosphorylation-independent manner. To explore the function of the Stat2-IFNaR2
      interaction and its possible relationship to the SH2-dependent docking of Stat2
      to phosphorylated IFNaR1, the affinity of Stat2 for each of the receptor subunits
      was determined. Recombinant proteins corresponding to the cytoplasmic domains of
      the receptor subunits and the central core region of Stat2 were partially
      purified and used in affinity precipitation experiments to demonstrate that Stat2
      binds more avidly to IFNaR2 than to phosphorylated IFNaR1. Surface plasmon
      resonance based biosensor analysis confirmed this finding; Stat2 bound IFNaR2
      (K(d) = 45 nM) approximately 6-fold stronger than it bound tyrosine 466
      phosphorylated IFNaR1 (K(d) = 245 nM). Affinity precipitation experiments
      involving all three proteins (Stat2, phosphorylated IFNaR1, and IFNaR2) indicated
      that the Stat2-receptor interactions are independent of one another. The
      relevance of these data to possible models of interferon alpha signal
      transduction is discussed.

PMID- 12220193
TI  - Coordinate binding studies of the substrate (factor X) with the cofactor (factor
      VIII) in the assembly of the factor X activating complex on the activated
      platelet surface.
AB  - The assembly of the factor X activating complex on the platelet surface requires
      the occupancy of three receptors: (1) enzyme factor IXa, (2) cofactor factor
      VIII(a), and (3) substrate factor X. To further evaluate this three-receptor
      model, simultaneous binding isotherms of (125)I-factor X and (131)I-factor
      VIII(a) to activated platelets were determined as a function of time and also as
      a function of the concentrations of both ligands in the presence of active site
      inhibited factor IXa (45 nM) and 5 mM CaCl(2). In the presence of active site
      inhibited factor IXa and factor VIIIa there are two independent factor X binding
      sites: (1) low affinity, high capacity (approximately 9000 sites/platelet; K(d)
      approximately 380 nM) and (2) low capacity, high affinity (1700 sites/platelet;
      K(d) approximately 30 nM). A single specific and selective factor X binding site
      was expressed (1200 sites/platelet; K(d) approximately 9 nM) when the shared
      factor X/factor II site was blocked by excess factor II (4 microM). In the
      presence of active site-inhibited factor IXa (4 nM) and factor II (4 microM),
      factor X binds to 3-fold more platelet sites than procofactor VIII with
      relatively low affinity (K(d) approximately 250 nM). The activation of
      procofactor VIII to factor VIIIa increases the affinity of binding to platelets
      of both factor VIIIa ( approximately 4-fold to K(d) approximately 0.8-1.5 nM) and
      factor X ( approximately 25-50-fold to K(d) approximately 5-9 nM). In the
      presence of excess zymogen factor IX, which blocks the shared factor IX/factor
      IXa binding site, the substrate, factor X, and the active cofactor, factor VIIIa,
      form a 1:1 stoichiometric complex. These coordinate binding studies support the
      conclusion that factor X initially binds to a high-capacity, low-affinity
      platelet binding site shared with prothrombin, which then presents factor X to a
      specific high-affinity site consisting of factor VIIIa bound to a high-affinity,
      low-capacity receptor on activated platelets.

PMID- 12220194
TI  - Site-directed mutagenesis of conserved charged amino acid residues in ClpB from
      Escherichia coli.
AB  - ClpB is a member of a multichaperone system in Escherichia coli (with DnaK, DnaJ,
      and GrpE) that reactivates strongly aggregated proteins. The sequence of ClpB
      contains two ATP-binding domains, each containing Walker consensus motifs. The N-
      and C-terminal sequence regions of ClpB do not contain known functional motifs.
      In this study, we performed site-directed mutagenesis of selected charged
      residues within the Walker A motifs (Lys212 and Lys611) and the C-terminal region
      of ClpB (Asp797, Arg815, Arg819, and Glu826). We found that the mutations K212T,
      K611T, D797A, R815A, R819A, and E826A did not significantly affect the secondary
      structure of ClpB. The mutation of the N-terminal ATP-binding site (K212T), but
      not of the C-terminal ATP-binding site (K611T), and two mutations within the C
      terminal domain (R815A and R819A) inhibited the self-association of ClpB in the
      absence of nucleotides. The defects in self-association of these mutants were
      also observed in the presence of ATP and ADP. The four mutants K212T, K611T,
      R815A, and R819A showed an inhibition of chaperone activity, which correlated
      with their low ATPase activity in the presence of casein. Our results indicate
      that positively charged amino acids that are located along the intersubunit
      interface (this includes Lys212 in the Walker A motif of the N-terminal ATP
      binding domain as well as Arg815 and Arg819 in the C-terminal domain) participate
      in intersubunit salt bridges and stabilize the ClpB oligomer. Interestingly, we
      have identified a conserved residue within the C-terminal domain (Arg819) which
      does not participate directly in nucleotide binding but is essential for the
      chaperone activity of ClpB.

PMID- 12220195
TI  - Detection of multiple active site domain motions in transient-state component
      time courses of the Clostridium symbiosum L-glutamate dehydrogenase-catalyzed
      oxidative deamination reaction.
AB  - We present a multiwavelength, transient-state kinetic study of the oxidative
      deamination reaction catalyzed by Clostridium symbiosum glutamate dehydrogenase
      (csGDH) producing the real-time reaction courses of spectroscopically resolved
      kinetically competent intermediate complexes. The results show striking
      differences from a corresponding transient-state study of the same reaction by
      the structurally homologous enzyme from beef liver (blGDH). In addition to the
      highly blue-shifted alpha-iminoglutarate and highly red-shifted carbinolamine
      complexes observed in both reactions, the csGDH reaction appeared to show the
      release of free NADH at a very early and mechanistically unlikely point in the
      reaction. Using lactic acid dehydrogenase as a "reporter" for free NADH, we show
      that the early portion of this signal reflects previously unobserved spectrally
      unshifted enzyme-bound NADH complexes. We provide experimental evidence to show
      that such spectrally anomalous complexes must represent forms of the known alpha
      imino and alpha-carbinolamine complexes in which the active site cleft is open.
      This evidence includes isothermal calorimetric measurements and pH-jump
      experiments that show the existence of differing two-state transitions in blGDH
      and csGDH and locate active site domain motions at differing points in the
      transient-state time courses of the two enzyme reactions. We prove the kinetic
      competence of a new and more highly detailed mechanism for the csGDH reaction
      that involves the alternation of open and closed enzyme complexes as integral
      steps. These findings, supported by the available X-ray crystal structure data,
      suggest the existence of a programmed time course of protein domain motions
      coordinated with the classically considered chemical time course. This new
      viewpoint may be presumed to be applicable to enzyme reactions other than those
      of the alpha-amino acid dehydrogenases.

PMID- 12220196
TI  - Expression and initial structural insights from solid-state NMR of the M2 proton
      channel from influenza A virus.
AB  - The M2 protein from influenza A virus has been expressed, purified, and
      reconstituted into DMPC/DMPG liposomes. SDS-PAGE analysis of reconstituted M2
      protein in DMPC/DMPG liposomes demonstrates a stable tetrameric preparation.
      Circular dichroism spectra of the intact M2 protein in detergent indicate 67%
      alpha-helix. The uniformly (15)N-labeled M2 protein and both (15)N-Val- and (15)N
      Leu-labeled M2 protein have been expressed from defined M9 media. The (1)H-(15)N
      HSQC (heteronuclear single quantum correlation) solution NMR experiments have
      been performed on the amino acid specific labeled protein in 300 mM SDS-d(25)
      micelles, and the data indicate a homogeneous preparation. The reconstituted
      M2/DMPC/DMPG proteoliposomes were used for preparing uniformly aligned solid
      state NMR samples for (15)N-(1)H dipolar/(15)N chemical shift correlation
      experiments. The spectra support a transmembrane helix in M2 protein having a
      tilt angle of approximate 25 degrees, quantitatively similar to results obtained
      on the isolated M2 transmembrane peptide reconstituted in DMPC bilayers (38
      degrees ). In addition, the spectra suggest that the tetrameric protein forms a
      symmetric or at least pseudosymmetric bundle consistent with data obtained by
      other research groups based on electrophysiological measurements and substituted
      cysteine scanning mutagenesis experiments that characterize a tetrameric
      structure.

PMID- 12220197
TI  - Localization of subunits D, E, and G in the yeast V-ATPase complex using cysteine
      mediated cross-linking to subunit B.
AB  - Using a combination of cysteine mutagenesis and covalent cross-linking, we have
      identified subunits in close proximity to specific sites within subunit B of the
      vacuolar (H(+))-ATPase (V-ATPase) of yeast. Unique cysteine residues were
      introduced into subunit B by site-directed mutagenesis, and the resultant V
      ATPase complexes were reacted with the bifunctional, photoactivatable maleimide
      reagent 4-(N-maleimido)benzophenone (MBP) followed by irradiation. Cross-linked
      products were identified by Western blot using subunit-specific antibodies.
      Introduction of cysteine residues at positions Glu(106) and Asp(199) led to cross
      linking of subunits B and E, at positions Asp(341) and Ala(424) to cross-linking
      of subunits B and D, and at positions Ala(15) and Lys(45) to cross-linking of
      subunits B and G. Using a molecular model of subunit B constructed on the basis
      of sequence homology between the V- and F-ATPases, the X-ray coordinates of the
      F(1)-ATPase, and energy minimization, Glu(106), Asp(199), Ala(15), and Lys(45)
      are all predicted to be located on the outer surface of the complex, with Ala(15)
      and Lys(45) located near the top of the complex furthest from the membrane. By
      contrast, Asp(341) and Ala(424) are predicted to face the interior of the
      A(3)B(3) hexamer. These results suggest that subunits E and G form part of a
      peripheral stalk connecting the V(1) and V(0) domains whereas subunit D forms
      part of a central stalk. Subunit D is thus the most likely homologue to the gamma
      subunit of F(1), which undergoes rotation during ATP hydrolysis and serves an
      essential function in rotary catalysis.

PMID- 12220198
TI  - Active site control of myosin cross-bridge zeta potential.
AB  - The electrical properties of contractile proteins contribute to muscle structure
      and perhaps function but have not been characterized adequately. Electrophoretic
      mobility, mu(e), is sensitive to the net electric charge and hydrodynamic size of
      a molecule in solution. Zeta potential, zeta, particle charge, Q(e), and particle
      charge-to-mass ratio are proportional to mu(e). We measured mu(e) for nucleotide
      complexes of skeletal muscle heavy meromyosin (HMM) and subfragment 1 (S1). The
      results indicate that mu(e) for HMM changes depending on the ligand bound in the
      active site. The changes in electric charge appear to occur mainly on the S1
      moieties. For HMM(MgATPgammaS)(2) and HMM(MgADP.P(i))(2) the values of mu(e) are 
      0.077 and -0.17 (microm/s)/(V/cm), respectively. For these complexes, mu(e) is
      independent of [ATP], [ADP], and [P(i)]. When P(i) dissociates from
      HMM(MgADP.P(i))(2) to form HMM(MgADP)(2), mu(e) decreases to -0.61
      (microm/s)/(V/cm). This large decrease in mu(e) is independent of free [ADP] or
      [ATP]. Increasing [P(i)], on the other hand, increases mu(e) for HMM(MgADP)(2) to
      values near those observed for the steady-state intermediate. For HMM, mu(e) = 
      0.34 and is independent of P(i). MgADP binding to HMM decreases mu(e) to -0.57
      (microm/s)/(V/cm), and the dissociation constant is 9 microM. Taken together,
      these data indicate that mu(e) and, thus, zeta are controlled by ligand binding
      to the active site. The magnitudes of the particle charge-to-mass ratios for the
      HMM complexes are all in a range that falls within published values determined
      for a variety of other proteins. Possible roles that the observed nucleotide
      dependent changes in cross-bridge electric charge might have in the contractile
      cycle in muscle are considered.

PMID- 12220199
TI  - Music therapy assessment for severely emotionally disturbed children: a pilot
      study.
AB  - The purpose of this study was to pilot a music therapy assessment instrument for
      severely emotionally disturbed children. The subjects in this pilot were 20
      children, 13 male and 7 female, at a residential treatment center in Cleveland,
      Ohio. After conducting an extensive literature review, the authors developed a
      music therapy assessment instrument measuring 4 relevant domains:
      behavioral/social functioning, emotional responsiveness, language/communication
      abilities, and music skills. Responses were coded into 3 categories:
      defensive/withdrawn, target behavior, and disruptive/intrusive. Results
      demonstrated that subjects displayed significantly more behaviors in the
      disruptive/intrusive domain. High inter-rater reliability scores of 91.5% for
      percent agreement and .808 for Cohen's kappa were achieved utilizing this
      assessment instrument.

PMID- 12220200
TI  - The relationship between type of degree and professional status in clinical music
      therapists.
AB  - The purpose of this descriptive study was to: (a) examine the relationship
      between the construct, Type of Music Therapy Degree, and 5 other constructs: Job
      Satisfaction, Job Longevity, Level of Promotion, Job Responsibilities, and
      Geographical Location; and (b) explore the interrelationships among the 5
      constructs other than Type of Music Therapy Degree. Questionnaires were mailed to
      616 clinical music therapists. The response rate was 35% (N = 218). Ten variables
      defining the 6 constructs were examined for statistically significant and
      meaningful relationships: highest music therapy degree achieved, average job
      satisfaction rating, length of time as a music therapist, length of time in
      present job, average length of time in jobs, total number of jobs, total number
      of promotions across jobs, number of present duties, number of hours presently
      working, and region in which work. Results indicated that a significant
      relationship existed between highest music therapy degree achieved and 3
      variables: length of time as a music therapist, total number of jobs, and region
      in which work. Follow-up comparisons revealed that those respondents with a
      Doctoral Degree had been employed at significantly more jobs than those with a
      Bachelor's degree. Also, those with a Master's degree in music therapy had stayed
      significantly longer in the field than those with a Bachelor's degree in music
      therapy. A follow-up analysis with the third variable, region in which work,
      indicated that the highest proportion of respondents in each region had obtained
      a Bachelor's degree in music therapy. Of the 8 significant relationships obtained
      among the other 9 variables, 4 variables defining the construct Job Longevity
      appeared to play a central role in the relationships among the variables.

PMID- 12220201
TI  - Beyond therapy: music, spirituality, and health in human experience: a review of
      literature.
AB  - In the current healthcare environment, there is a growing interest in the
      relationship between spirituality and health. The connections between music and
      both medicine and religious experience are well-established, but little is known
      about how the musical and spiritual aspects of human experience work together to
      influence well-being. A review of the healthcare literature from 1973-2000
      identified 52 published reports on the topic of music, spirituality, and health.
      The majority of the papers were narrative descriptions or case studies, and
      appear within a variety of clinical contexts. Fifty-two percent of the authors
      were credentialed music therapists. Examination of the literature indicated that
      many papers used terms and concepts associated with both spirituality and health
      interchangeably, which might lend support to the basic interconnectedness of
      these two aspects of being. The function of music across the literature was
      explored, and a transformational model of music experience derived from the
      literature is proposed. Based on the findings of the review, several conclusions
      about the future role of music in spirituality and health are drawn, and
      recommendations for further research are offered.

PMID- 12220202
TI  - Is the party over?

PMID- 12220203
TI  - A staging system for congenital cholesteatoma.
AB  - OBJECTIVE: To develop a staging system for congenital cholesteatoma in predicting
      the likelihood of residual disease. DESIGN: Retrospective analysis of data from a
      case series, to identify predictors of residual disease. SETTING: Tertiary care
      pediatric hospital. PARTICIPANTS: Children undergoing surgical removal of
      congenital cholesteatoma. There were 156 patients, with 160 cholesteatomas; 4
      children had bilateral disease. INTERVENTIONS: Each case was scored as to
      quadrants of the middle ear involved, ossicular involvement, and mastoid
      extension. MAIN OUTCOME MEASURE: Surgically confirmed residual disease at any
      time after the initial procedure. RESULTS: Four stages were defined as follows:
      stage I, disease confined to a single quadrant; stage II, cholesteatoma in
      multiple quadrants, but without ossicular involvement or mastoid extension; stage
      III, ossicular involvement without mastoid extension; and stage IV, mastoid
      disease. There was a strong association between stage and residual disease,
      ranging from a 13% risk in stage I to 67% in stage IV. CONCLUSIONS: This simple
      staging system may be particularly useful in standardizing the reporting of
      congenital cholesteatoma and in adjusting for severity in evaluating outcomes. It
      also provides information that is useful in counseling parents.

PMID- 12220204
TI  - Cochlear implantation in children with CHARGE association.
AB  - OBJECTIVE: To explore the anomalies of the temporal bone found on radiologic
      examination, technical challenges in cochlear implantation, and audiologic
      benefit derived from cochlear implantation in a series of children with CHARGE
      association. DESIGN: Case series report. SETTING: Tertiary referral children's
      hospital pediatric cochlear implant program. PATIENTS: Six children with CHARGE
      association and sensorineural hearing loss. INTERVENTION: All patients were
      evaluated and followed up by the cochlear implant team. Cochlear implantation was
      attempted in all 6 children. MAIN OUTCOME MEASURES: Computed tomographic scans
      and cochlear implantation operative records were reviewed, and their findings
      were correlated. Audiometric and speech perception data before and after cochlear
      implantation were compared. RESULTS: Five children with CHARGE association
      received implants. A sixth child did not because of an aberrant course to the
      facial nerve. The 5 children receiving implants obtained varying degrees of
      measurable benefit from their implants. All 6 children had temporal bone
      abnormalities seen on their computed tomographic scans and documented at the time
      of surgery. CONCLUSIONS: Variations in the temporal bone anatomy of patients with
      CHARGE association can lead to increased technical challenges and risk to the
      facial nerve during cochlear implantation. Individual outcomes after implantation
      may vary; our patients receiving implants obtained benefit. Parents should be
      counseled thoroughly and have appropriate expectations before proceeding with
      implantation.

PMID- 12220205
TI  - A technique for implantation of a 3-dimensional penetrating electrode array in
      the modiolar nerve of cats and humans.
AB  - BACKGROUND: We believe that direct intraneural stimulation of the modiolar nerve
      using an array of electrodes will have lower thresholds, offer greater frequency
      selectivity and more stimulation sites, and have a greater frequency
      representation than conventional cochlear implants. OBJECTIVES: To describe a
      potential auditory prosthesis based on electrical stimulation of the modiolar
      cochlear nerve and to report the development of a surgical approach in human and
      animal models. DESIGN: Cadaveric human and animal studies conducted in temporal
      bones indicated that an array of penetrating microelectrodes could be implanted
      in the modiolar nerve. Cat studies using anesthesia were performed to develop the
      surgical procedure in an animal model. Nerve viability was assessed by
      measurement of electrically evoked auditory brainstem responses at different
      stages of the surgery. SUBJECTS: Two fresh cadaveric human temporal bones, 3 cat
      cadavers, 1 pig cadaver, and 6 anesthetized cats were used in the experiments.
      RESULTS: We were able to implant arrays containing 20 microelectrodes in the
      human modiolar nerve after exposure by a modified extended facial recess
      approach. In animals, the modiolar nerve was accessed by the transbulla and the
      middle fossa approach. The cat was chosen as the appropriate animal model, and
      the transbulla approach was selected. The round window was exposed by ventral
      access to the bulla and after cochleostomy; drilling the modiolar bone exposed
      the modiolar nerve. The mean +/- SD diameter of the exposed nerve in cats was
      1.64 +/- 0.07 mm (n = 9), and the mean +/- SD exposed length was 2.50 +/- 0.11 mm
      (n = 9); this is adequate to accommodate 20 microelectrodes. The electrically
      evoked auditory brainstem responses indicated nerve survival during and after the
      surgery. CONCLUSIONS: The surgical technique allows implantation of up to 20
      microelectrodes in the cat and human modiolar nerve. The nerve survives the
      surgical procedure. This work enables studies in the electrophysiological
      properties and consequences of long-term implantation.

PMID- 12220206
TI  - Clinical and audiological features in auditory neuropathy.
AB  - OBJECTIVE: To medically and audiologically characterize a population of children
      diagnosed as having auditory neuropathy (AN). STUDY DESIGN: Retrospective medical
      chart review. SETTING/SUBJECTS: We identified 22 patients from a pediatric
      otology clinic in a tertiary care pediatric hospital setting. RESULTS: A genetic
      factor in AN is suggested by our identification of 3 families with 2 affected
      children and 2 other children with family histories that were positive for
      hearing loss. Clinical features common among our population included a history of
      hyperbilirubinemia (n = 11 [50%]), prematurity (n = 10 [45%]), ototoxic drug
      exposure (n = 9 [41%]), family history of hearing loss (n = 8 [36%]), neonatal
      ventilator dependence (n = 8 [36%]), and cerebral palsy (n = 2 [9%]). Full
      clinical and audiological data were available for 18 of the 22 children,
      including otoacoustic emissions, auditory brainstem responses with cochlear
      microphonics, and age-appropriate audiometric findings. Significantly, 9 of these
      18 patients showed improvement in behavioral thresholds over time, indicating
      that a subset of children with AN may recover useful hearing levels. Also
      significant was the success of cochlear implantation in 4 children. CONCLUSIONS:
      Management of AN in children requires serial clinical and audiometric
      evaluations, with a prominent role for behavioral testing. Prematurity, genetics,
      and hyperbilirubinemia appear to be significant factors in the development of AN;
      hyperbilirubinemia can be associated with spontaneous improvement of hearing
      thresholds. For those children not benefiting from amplification or FM systems,
      cochlear implantation remains a potentially successful method of habilitation.

PMID- 12220207
TI  - Inner ear anomalies are frequent but nonobligatory features of the branchio-oto
      renal syndrome.
AB  - OBJECTIVE: To summarize the syndromic features and evaluate the presence of inner
      ear anomalies in 35 patients with branchio-oto-renal (BOR) syndrome from 6
      families. DESIGN: Retrospective evaluation of magnetic resonance imaging of the
      temporal bones and clinical features in patients with BOR syndrome. SETTING:
      Tertiary referral center. PATIENTS: The study population comprised 35 clinically
      affected patients with BOR syndrome from 6 families. Most of these families were
      followed for over 25 years. MAIN OUTCOME MEASURES: Twenty-four patients underwent
      high-resolution, heavily T2-weighted 3-dimensional magnetic resonance imaging of
      the temporal bones for evaluation of inner ear anomalies. Special attention was
      paid to the endolymphatic duct and sac. RESULTS: A total of 7 enlarged
      endolymphatic ducts and sacs (3 bilaterally and 4 unilaterally) and 5 enlarged
      endolymphatic ducts only (2 bilaterally and 3 unilaterally) were observed. Eight
      hypoplastic cochleas and 6 hypoplastic labyrinths were seen bilaterally. Seven
      family members had normal inner ears. CONCLUSION: These findings suggest that
      inner ear anomalies are frequent but nonobligatory features of BOR syndrome.

PMID- 12220208
TI  - Anesthetic complications of tympanostomy tube placement in children.
AB  - OBJECTIVE: To determine the incidence of perioperative anesthesia complications
      during bilateral myringotomy with tympanostomy tube placement (BMTT). SETTING:
      Tertiary care children's hospital where otolaryngology attending physicians and
      residents performed surgical procedures. Anesthesia providers included pediatric
      anesthesiologists, residents, nurse anesthetists, and students. METHODS: Medical
      record review was performed for a consecutive series of 3198 children undergoing
      BMTT (1000 prospectively, 2198 retrospectively). For the prospectively studied
      patients, major adverse events, which included laryngospasm and stridor, and
      minor adverse events, including upper airway obstruction, prolonged recovery,
      emesis, and persistent postprocedural agitation, were noted. Also recorded were
      the patient's American Society of Anesthesiologists (ASA) physical class status,
      age, concurrent medical conditions, and type of anesthesia provider. RESULTS:
      Fewer than 9% of prospectively studied pediatric patients experienced a minor
      adverse event, whereas a major event occurred in 1.9%. Eighty-one percent of the
      events experienced were attributable to agitation or prolonged recovery. Neither
      ASA status (P =.38), age (P =.15), nor type of anesthesia provider (P =.06) were
      significantly related to the occurrence of an adverse event. However, a child
      with an acute or chronic illness has 2.78 times the odds of experiencing an
      adverse event compared with a child with no illness (P<.001). CONCLUSIONS:
      Anesthesia administered for placement of tympanostomy tubes by physicians who
      specialize in the care of children in a tertiary care children's hospital is
      safe. The most significant predictor of a minor anesthetic event during BMTT is
      the presence of a preexisting medical condition or concurrent acute illness.

PMID- 12220209
TI  - Comparison of head thrust test with head autorotation test reveals that the
      vestibulo-ocular reflex is enhanced during voluntary head movements.
AB  - OBJECTIVES: To compare 2 clinical tests of vestibular function, the head
      autorotation test (HART) and the head thrust test (HTT), and to determine why
      they give disparate results in patients with known unilateral vestibular
      deficiency (UVD) due to labyrinthectomy. METHODS: We used scleral coils to
      measure the horizontal (yaw) vestibulo-ocular reflex (VOR) in 5 healthy human
      subjects and in 11 patients who underwent labyrinthectomy. We used 2 paradigms.
      Using HART, subjects visually fixated a target during self-generated, swept
      frequency, sinusoidal, horizontal head rotations. Using HTT, patients fixated the
      target during horizontal head thrusts delivered randomly in direction and time.
      RESULTS: In subjects without UVD, eye movements were almost perfectly
      compensatory for both paradigms. In subjects with UVD, VOR gain for ipsilesional
      head thrusts was low for both paradigms, but significantly (P<.001) higher (less
      abnormal) for HART (0.60 +/- 0.13) than for HTT (0.14 +/- 0.13). Contralesional
      gain was reduced for both, to 0.64 +/- 0.20 for HART and to 0.57 +/- 0.17 for
      HTT. Because ipsilesional and contralesional gains were not statistically
      different for HART (P =.69), comparison of VOR gains for half-cycle responses to
      the HART stimulus could not reliably identify the side of the known lesion. In
      contrast, HTT consistently identified the side of the lesion for all subjects
      with UVD. To investigate whether preprogramming contributes to the boost in VOR
      as measured by HART, we compared the gain and response delay of eye movements
      during actively self-generated and passively received head thrusts. For subjects
      without UVD, response delays were shorter for active (6 +/- 1 milliseconds) than
      for passive (12 +/- 1 milliseconds) HTT. For ipsilesional rotations of subjects
      with UVD, active HTT yielded a significantly higher gain (0.44 +/- 0.20) (P<.001)
      and a shorter delay (15 +/- 6 milliseconds) (P<.001) than did passive HTT (0.14
      +/- 0.13 and 37 +/- 15 milliseconds, respectively). Contralesional test results
      revealed a similar performance boost for active head movements. Data are given as
      mean +/- SD. CONCLUSION: When comparison of half-cycle gains is used to identify
      the lesion side, self-generated predictable head movement paradigms, such as HART
      and active HTT, are less accurate than passive HTT in the characterization of
      UVD, in part because preprogramming can augment the VOR during voluntary head
      movements.

PMID- 12220211
TI  - The role of free radicals in chronic rhinosinusitis.
AB  - OBJECTIVE: To determine whether there is an increased amount of free radical
      mediated damage in diseased vs healthy tissue from patients with chronic
      rhinosinusitis. DESIGN: Pathophysiologic study. Samples of heathly and diseased
      tissue were taken from each patient. Lipid peroxides (LPOs) are a by-product of
      free radical-mediated damage; LPO levels and LPO/protein ratios were determined
      for each patient. SUBJECTS: Consecutive series of 13 human subjects undergoing
      functional endoscopic sinus surgery to treat chronic rhinosinusitis. RESULTS: The
      mean LPO/protein ratio for healthy tissue was 3.52 x 10(-5), while that for the
      diseased tissue was 3.49 x 10(-5). There was no statistically significant
      difference in the LPO/protein ratio between healthy and diseased tissue (95%
      confidence interval, -3.00 x 10(-5) to 2.94 x 10(-5)). CONCLUSION: Free radical
      induced damage, if present, was the same in infected and control tissues in this
      pilot investigation into the pathophysiologic characteristics of human chronic
      rhinosinusitis.

PMID- 12220212
TI  - Decrease of specific and total IgE levels in allergic patients after BCG
      vaccination: preliminary report.
AB  - BACKGROUND: A systemic reaction to mycobacteria biases the balance of T helper
      cell types 1 and 2 toward T helper cell type 1. BCG vaccination mimics some
      characteristics of mycobacterial infection. Children who have undergone
      tuberculin conversion after BCG vaccination seem to be more likely to lose their
      atopic symptoms. Inhibition of both allergic response and airway hyperreactivity
      after vaccination for mycobacteria has been observed in animal experiments.
      OBJECTIVE: To evaluate the effects that BCG vaccination has on the serological
      status of allergic people. PARTICIPANTS AND METHODS: This study included 20
      volunteers with a history of allergic rhinitis who were required to undergo BCG
      vaccination by Italian law. Epicutaneous allergy testing with a panel of common
      seasonal and perennial inhalational allergens and 2 blood withdrawals were
      performed. The serum total IgE levels and the serum allergen-specific IgE levels
      of each individual were measured just before BCG vaccination and again 4 months
      later. Total IgE levels were determined using the paper radioimmunosorbent test,
      and allergen-specific IgE levels were determined using the radioallergosorbent
      test. RESULTS: Total IgE and allergen-specific IgE levels were significantly
      decreased after BCG vaccination (P =.004 and P<.001, respectively). CONCLUSION:
      BCG, an effective stimulus for cell-mediated immunity, deserves further study to
      evaluate its ability to modulate the immune response associated with allergic
      rhinitis.

PMID- 12220213
TI  - Differing pathways of lower airway colonization and infection according to mode
      of ventilation (endotracheal vs tracheotomy).
AB  - OBJECTIVES: To determine whether the pathogenesis of lower airway colonization
      and infection was endogenous (via the oropharynx) or exogenous (via the
      endotracheal tube or tracheotomy) during the 2 modes of ventilation in the same
      subset of children requiring long-term ventilation. DESIGN: Prospective,
      observational cohort study. SETTING: A pediatric intensive care unit and a
      respiratory ward. PATIENTS: Consecutive admissions between September 1, 1993, and
      August 30, 1998. MEASUREMENTS AND MAIN RESULTS: Cultures were obtained
      simultaneously from the oropharynx and tracheobronchial tree on admission to the
      pediatric intensive care unit, at placement of the tracheotomy, and afterward
      twice weekly. Forty-five patients were studied. Lower airways were always sterile
      in 6 children, 39 children (87%) developed a total of 82 episodes of
      colonization, and 17 (38%) progressed to 25 episodes of infection. The number of
      infected children was halved once they had a tracheotomy (7 children [16%]). Of
      the 107 episodes of colonization and infection, 41 and 66 occurred during
      endotracheal ventilation and via a tracheotomy, respectively. Primary endogenous
      episodes of colonization and infection due to bacteria present in the admission
      flora in the pediatric intensive care unit were significantly more common with
      endotracheal ventilation than during ventilation via a tracheotomy (31/41 [76%]
      vs 36/66 [55%]; P =.03). Secondary endogenous and exogenous episodes of
      colonization and infection due to bacteria associated with the respiratory ward
      were significantly more frequent when ventilation was continued through a
      tracheotomy than during endotracheal ventilation (30/66 [45%] vs 10/41 [24%]; P
      =.02). CONCLUSIONS: Surveillance samples allow the distinction between primary
      endogenous ("imported" bacteria) from secondary endogenous and exogenous
      ("nosocomial" microorganisms) colonization and infection. This classification
      permits the development of preventive strategies to control both endogenous and
      exogenous pathways.

PMID- 12220214
TI  - Long-term survival outcome in transhyoid resection of base of tongue squamous
      cell carcinoma.
AB  - BACKGROUND: The transhyoid approach for the resection of squamous cell carcinoma
      (SCC) of the base of the tongue continues to evolve and remains controversial. We
      previously reported that the functional outcome of this operation is superior to
      that of the traditional transmandibular approaches. OBJECTIVE: To report our long
      term survival rates for T1, T2, and select T3 SCCs of the base of the tongue
      using the transhyoid approach. PATIENTS AND METHODS: Twenty-eight patients with
      SCC of the base of the tongue were treated using a transhyoid approach at the
      University of California, Los Angeles, Medical Center between 1981 and 1998.
      RESULTS: All 28 patients underwent simultaneous neck dissection, and 27 patients
      underwent postoperative radiation therapy. The majority of the patients had
      advanced stage III or IV SCC. Twenty-five of the 28 patients had clear margins in
      the final pathologic specimen. The overall 3- and 5-year patient survival rates
      were 88.5% and 80.0%, respectively. Tumor-specific 5-year survival rates were
      80.0%, 84.6%, and 50.0% for T1, T2, and T3 tumors, respectively. Stage-specific 5
      year survival rates were 60.0%, 100.0%, and 80.0% for stages II, III, and IV,
      respectively. CONCLUSIONS: The advantages of the transhyoid approach to SCC of
      the base of the tongue in conjunction with neck dissection and postoperative
      radiation therapy include excellent long-term patient survival, improved
      swallowing and speech function, outstanding tumor exposure, and minimal cosmetic
      deformity.

PMID- 12220215
TI  - Craniofacial resection of advanced juvenile nasopharyngeal angiofibroma.
AB  - OBJECTIVE: To describe the results of a craniofacial approach to resection of
      stage IIIB juvenile nasopharyngeal angiofibroma, performed by an integrated skull
      base surgical team. DESIGN: A retrospective case-series review was conducted with
      postoperative follow-up ranging from 28 to 63 months. SETTING: Operations were
      performed at a tertiary medical center. PATIENTS: A referred sample of 5 male
      patients, ranging in age from 10 to 23 years (mean, 15 years). INTERVENTIONS: All
      patients underwent resection of nasopharyngeal angiofibromas with intracranial
      extension. The procedure involved an infratemporal fossa approach via zygomatic
      osteotomy and subtemporal craniectomy. Anterior exposure was gained through a
      standard facial translocation. Dissection of the cavernous carotid artery was
      required in 3 patients. MAIN OUTCOME MEASURES: Intraoperative and postoperative
      morbidity. RESULTS: The average operating time was 12 hours 47 minutes. Estimated
      blood loss ranged from 700 to 1750 mL (mean, 1120 mL), with 2 patients requiring
      intraoperative transfusion. Patients were hospitalized for a mean duration of 5.6
      days. Long-term morbidity includes facial dysesthesia, nasal crusting, and
      malodorous nasal discharge. No patients sustained stroke, oculomotor dysfunction,
      vision loss, or auditory impairment. At most recent follow-up, which ranges from
      28 to 63 months, tumor recurrence has been confirmed in 1 patient. CONCLUSIONS: A
      combined craniofacial approach is appropriate for juvenile nasopharyngeal
      angiofibroma that extends intracranially. Complete tumor removal with acceptable
      morbidity can be expected.

PMID- 12220216
TI  - Cancer of the nasal cavity: survival and factors influencing prognosis.
AB  - OBJECTIVE: To determine overall survival and prognostic factors for cancer of the
      nasal cavity. DESIGN: Cross-sectional analysis of a national cancer database.
      METHODS: All cases of nasal cavity cancer were extracted from the Surveillance,
      Epidemiology and End Results database for 1988 through 1998. Cases with distant
      metastatic disease were excluded. Tumor histologic types, TNM staging, and
      pathological features were computed. Kaplan-Meier and Cox proportional hazards
      analyses were conducted to determine factors influencing overall survival.
      RESULTS: A total of 981 cases were identified, with 3.5% presenting with distant
      metastatic disease. After exclusion of missing variables, 783 cases were
      analyzed, with a mean patient age of 63.8 years. Squamous cell carcinoma was the
      most common tumor histologic type (49.3%), followed by esthesioneuroblastoma
      (13.2%). More than half of the cases presented with early (T1) primary site
      disease, and only 5% had positive nodal disease at presentation. Overall mean
      (median) survival was 76 (81) months, with an overall 5-year survival rate of
      56.7%. On multivariate analysis, male sex, increasing age, T stage, N stage, and
      poorer tumor grade independently adversely affected survival (P<.05).
      Radiotherapy was administered in 50.5% of patients and also independently
      predicted poorer survival (P =.03). The mean (median) survival for squamous cell
      carcinoma was 79 (84) months; only melanoma showed a statistically significantly
      poorer mean survival of 40 (30) months when compared with other tumors (P<.001).
      CONCLUSIONS: Age, sex, and staging variables have a significant prognostic impact
      in nasal cavity cancer. Melanomas of the nasal cavity manifest very poor
      survival.

PMID- 12220218
TI  - Clear cell odontogenic carcinoma: report of a case and analysis of the
      literature.
AB  - BACKGROUND: Clear cell odontogenic carcinoma (CCOC), which has been described
      within the past 2 decades, is a rare odontogenic tumor that tends to occur in the
      mandible of older adults, with a predilection for women. It is potentially
      aggressive and capable of multiple local recurrences and locoregional and distant
      metastases. OBJECTIVES: To report the clinicopathologic findings and follow-up of
      a case of CCOC and to review the literature. DESIGN: Case report and literature
      review. MAIN OUTCOME MEASUREMENTS: Findings from histologic analysis,
      immunohistochemistry, and electron microscopy. RESULTS: An 81-year-old woman
      experienced 3 locoregional recurrences within 21 months of initial therapy. She
      is presently disease free, 4.5 years after initial resection, having received
      multiple resections and adjuvant radiotherapy. CONCLUSIONS: The diagnosis of CCOC
      must be considered in the differential diagnosis of jaw tumors with a clear cell
      component. For these tumors, resection with negative margins is the treatment of
      choice because more conservative surgery (eg, curettage) inevitably results in
      recurrence and/or metastasis. Adjuvant radiotherapy is a rational option for
      tumors that have eroded cortex.

PMID- 12220217
TI  - DNA repair gene ERCC1 and ERCC2/XPD polymorphisms and risk of squamous cell
      carcinoma of the head and neck.
AB  - OBJECTIVE: To determine the effect of the ERCC1 C8092A polymorphism and the
      ERCC2/XPD G23591A polymorphism on the risk of squamous cell carcinoma of the head
      and neck (SCCHN). DESIGN: A hospital-based case-control study. SUBJECTS: A total
      of 330 newly diagnosed case subjects with SCCHN and 330 cancer-free control
      subjects matched on age (+/- 5 years), sex, smoking status, and alcohol use. All
      subjects were non-Hispanic whites. METHODS: After informed consent was obtained,
      blood was drawn for genotyping. The ERCC1 C8092A polymorphism was typed by single
      strand conformational polymorphism analysis. The ERCC2/XPD G23591A polymorphism
      was typed by polymerase chain reaction-based restriction fragment length
      polymorphism analysis with the enzyme StyI. The chi(2) analysis was used to
      assess differences in genotype and allele frequencies. Multivariate logistic
      regression analysis was performed to estimate the risk of SCCHN for individuals
      having these genotypes after adjustment for age, sex, tobacco smoking, and
      alcohol use. RESULTS: The DNA was available and genotyping was ultimately
      successful for 313 case subjects and 313 control subjects. The ERCC1 8092CC
      genotype and the ERCC2/XPD 23591A allele were associated with nonsignificantly
      increased risks of SCCHN: odds ratios, 1.15 (95% confidence interval [CI], 0.84
      1.59) and 1.28 (95% CI, 0.93-1.76), respectively, whereas having both risk
      genotypes was associated with an even higher risk of SCCHN: odds ratio, 1.78 (95%
      CI, 0.99-3.17). When considering both polymorphisms, we found a significant
      allele dose effect (P =.04). CONCLUSIONS: These 2 polymorphisms may contribute to
      the risk of SCCHN, but larger studies are needed to confirm their role in SCCHN.
      Combining common DNA repair gene polymorphisms into models of genetic risk of
      SCCHN may improve risk estimates.

PMID- 12220219
TI  - Failed extraction of a sharp esophageal foreign body with a flexible endoscope: a
      case report and review of the literature.
AB  - Several methods for the extraction of esophageal foreign bodies have been
      described. The most common approaches use either the flexible fiberoptic
      esophagoscope or the rigid esophagoscope. We report an unusual complication
      following the attempted extraction of a sharp esophageal foreign body with a
      flexible esophagoscope, review the indications for these 2 methods of extraction,
      and discuss the potential morbidity and mortality of these 2 approaches.

PMID- 12220220
TI  - Pathology quiz case 1. Actinomycosis of the submandibular area mimicking a
      malignancy.

PMID- 12220221
TI  - Pathology quiz case 2. Odontogenic keratocyst (OKC).

PMID- 12220222
TI  - Radiology quiz case 1. Cervical extension of an EAC cholesteatoma.

PMID- 12220223
TI  - Radiology quiz case 2. Chiari malformation (type I).

PMID- 12220224
TI  - Transport of bile acids in multidrug-resistance-protein 3-overexpressing cells co
      transfected with the ileal Na+-dependent bile-acid transporter.
AB  - Many of the transporters involved in the transport of bile acids in the
      enterohepatic circulation have been characterized. The basolateral bile-acid
      transporter of ileocytes and cholangiocytes remains an exception. It has been
      suggested that rat multidrug resistance protein 3 (Mrp3) fulfills this function.
      Here we analyse bile-salt transport by human MRP3. Membrane vesicles from insect
      ( Spodoptera frugiperda ) cells expressing MRP3 show time-dependent uptake of
      glycocholate and taurocholate. Furthermore, sulphated bile salts were high
      affinity competitive inhibitors of etoposide glucuronide transport by MRP3 (IC50
      approximately 10 microM). Taurochenodeoxycholate, taurocholate and glycocholate
      inhibited transport at higher concentrations (IC50 approximately 100, 250 and 500
      microM respectively). We used mouse fibroblast-like cell lines derived from mice
      with disrupted Mdr1a, Mdr1b and Mrp1 genes to generate transfectants that express
      the murine apical Na+-dependent bile-salt transporter (Asbt) and MRP3. Uptake of
      glycocholate by these cells is Na+-dependent, with a K(m) and V(max) of 29+/-7
      microM and 660 +/- 63 pmol/min per mg of protein respectively and is inhibited by
      several organic-aniontransport inhibitors. Expression of MRP3 in these cells
      limits the accumulation of glycocholate and increases the efflux from cells
      preloaded with taurocholate or glycocholate. In conclusion, we find that MRP3
      transports both taurocholate and glycocholate, albeit with low affinity, in
      contrast with the high-affinity transport by rat Mrp3. Our results suggest that
      MRP3 is unlikely to be the principal basolateral bile-acid transporter of
      ileocytes and cholangiocytes, but that it may have a role in the removal of bile
      acids from the liver in cholestasis.

PMID- 12220225
TI  - Role of the protein tyrosine phosphatase SHP-1 (Src homology phosphatase-1) in
      the regulation of interleukin-3-induced survival, proliferation and signalling.
AB  - The tyrosine phosphatase SHP-1 (Src homology phosphatase-1) has been widely
      implicated as a negative regulator of signalling in immune cells. We have
      investigated in detail the role of SHP-1 in interleukin-3 (IL-3) signal
      transduction by inducibly expressing wild-type (WT), C453S (substrate-trapping)
      and R459M (catalytically inactive) forms of SHP-1 in the IL-3-dependent cell line
      BaF/3. Expression of WT SHP-1 had little impact on IL-3-induced proliferation,
      but enhanced apoptosis following IL-3 withdrawal. Expression of R459M SHP-1
      increased the proliferative response of BaF/3 cells to IL-3 and increased cell
      survival at low doses of IL-3 and following IL-3 withdrawal. Investigation into
      the biochemical consequences resulting from expression of these SHP-1 variants
      demonstrated that the beta chain of the IL-3 receptor (Aic2A) was hypo
      phosphorylated in cells expressing WT SHP-1 and hyper-phosphorylated in those
      expressing R459M SHP-1. Further, ectopic expression of the trapping mutant, C453S
      SHP-1, protected Aic2A from dephosphorylation, suggesting that Aic2A is a SHP-1
      substrate in BaF/3 cells. Examination of overall levels of tyrosine
      phosphorylation demonstrated that they were not perturbed in these transfectants.
      Activation-specific phosphorylation of STAT (signal transducer and activator of
      transcription) 5a/b, protein kinase B and ERK (extracellular-signal-regulated
      kinase)-1 and -2 was also unaffected by expression of WT or R459M SHP-1. However,
      overall levels of IL-3-induced tyrosine phosphorylation of STAT5 were reduced
      upon expression of WT SHP-1 and increased when R459M SHP-1 was expressed,
      consistent with STAT5 being a potential SHP-1 substrate. These results
      demonstrate that SHP-1 acts to negatively regulate IL-3-driven survival and
      proliferation, potentially via regulation of tyrosine phosphorylation of Aic2A
      and STAT5.

PMID- 12220226
TI  - Active Snf1 protein kinase inhibits expression of the Saccharomyces cerevisiae
      HXT1 glucose transporter gene.
AB  - Expression of HXT1, a gene encoding a Saccharomyces cerevisiae low-affinity
      glucose transporter, is regulated by glucose availability, being activated in the
      presence of glucose and inhibited when the levels of the sugar are scarce. In
      this study we show that Snf1 protein kinase participates actively in the
      inhibition of HXT1 expression. Activation of Snf1, either by physiological
      conditions (growth in low-glucose conditions) or by eliminating any of its
      negative regulators, such as Hxk2 or Reg1, leads to an inhibition of HXT1
      expression. We also show that Std1, another known negative regulator of HXT1
      expression, interacts physically with active Snf1 protein kinase. Std1 also
      interacts physically with Rgt1, a transcription factor involved in HXT1
      expression, suggesting that the transcriptional properties of Rgt1 could be
      modulated either directly or indirectly by Std1 and Snf1 protein kinase. Finally,
      we show that Rgt1 interacts physically with Ssn6, a major transcriptional
      repressor, to regulate negatively HXT1 expression when glucose is depleted.

PMID- 12220228
TI  - Age-related disease pattern in infertile men: increasing incidence of infections
      in older patients.
AB  - In a cross-sectional retrospective study, the age-dependency of semen parameters
      of men with specific andrological diseases was investigated in 3,698 men (mean
      age 33 years; range 19-63 years) attending a tertiary referral clinic for couple
      infertility. In all, 1,853 patients suffered from idiopathic infertility (mean
      age 33.2 years; range 19-60 years), 388 from infections of the accessory glands
      (34.2; 20-61), 363 had a history of maldescended testes (32.0; 20-51) and 833 a
      varicocele (33.6; 20-63). In 172 patients, a varicocele and an infection (34.3;
      24-54) and in 94 a varicocele and a history of maldecended testes (32.5; 21-53)
      were found. Semen analysis was performed according to WHO criteria. An age
      related decrease in testicular volume was not observed in any group. Total sperm
      count decreased significantly with advancing age only in patients with an
      infection of the accessory glands. We found no evidence for age-dependent
      progressive deterioration of semen variables in the other groups. It may be
      concluded that the causes for the spermatogenetic defects in men with idiopathic
      infertility, a history of maldescended testes or varicocele are acquired before
      adolescence and do not progress during adulthood. In contrast, infections of the
      accessory glands may lead to decreased sperm counts by functional impairment or
      partial occlusion of the seminal ducts. Thus, if in the general population
      declining sperm counts are observed, genital tract infections may be suspected as
      a contributing factor.

PMID- 12220229
TI  - Use of a highly sensitive quantitative telomerase assay in intracytoplasmic sperm
      injection programmes for the treatment of 47,XXY non-mosaic Klinefelter men.
AB  - We evaluated the role of the sensitive quantitative telomerase assay (SQTA) in
      the management of men with non-mosaic Klinefelter's syndrome (KS). Diagnostic
      testicular biopsy (DTB) was performed in 24 men with KS. A part of the DTB was
      stained and the remaining fragment was processed for the SQTA. After 3-18 months,
      a therapeutic testicular biopsy (TTB) was performed in the same testicle and the
      recovered specimens were processed to identify spermatozoa. Men with a SQTA
      outcome equal to 0.00 Units microg-1 protein (n = 7) demonstrated therapeutic
      testicular biopsy material that was negative for spermatogenic cells. In five men
      with a SQTA outcome of 8.11-38.03 Units microg-1, the most advanced germ cell was
      the spermatogonium/primary spermatocyte. In the remaining 12 men, the most
      advanced spermatogenic cell in the TTB was the spermatozoon. In these men, the
      SQTA outcome was equal to 25.76-92.68 Units microg-1 protein. Using 39.00 Units
      microg-1 protein as a cut-off value, the accuracy of the SQTA in identifying men
      positive for spermatozoa was 91.6%. It appears that the SQTA has a role for
      identifying non-mosaic KS men who have testicular spermatozoa.

PMID- 12220227
TI  - Reciprocal feedback regulation of insulin receptor and insulin receptor substrate
      tyrosine phosphorylation by phosphoinositide 3-kinase in primary adipocytes.
AB  - Signalling by the insulin receptor substrate (IRS) proteins is critically
      dependent on the tyrosine phosphorylation of specific binding sites that recruit
      Src homology 2 (SH2)-domain-containing proteins, such as the p85 subunit of
      phosphoinositide 3-kinase (PI 3-kinase), the tyrosine phosphatase SHP-2 and the
      adapter protein Grb2. Here we show that stimulation by insulin of freshly
      isolated primary adipocytes resulted in the expected rapid tyrosine
      phosphorylation of the insulin receptor, IRS-1 and IRS-3. Inhibition of PI 3
      kinase enhanced the insulin-stimulated phosphorylation of IRS-1 on (i) Tyr(612)
      and Tyr(941) (p85 binding sites), concomitant with an increased association of
      the p85 subunit of PI 3-kinase; (ii) Tyr(896) (a Grb2 binding site); and (iii)
      Tyr(1229) (an SHP-2 binding site), although little or no binding of SHP-2 to IRS
      1 was detectable under any conditions. In contrast, inhibition of PI 3-kinase led
      to a decrease in insulin-stimulated p85 binding to IRS-3, but had no effect on
      SHP-2 binding. Furthermore, insulin-induced insulin receptor tyrosine
      phosphorylation, phosphorylation of Tyr(1158) and insulin receptor tyrosine
      kinase activity were all reduced by inhibition of PI 3-kinase at later time
      points (>or=20 min). The results demonstrate that, in primary adipocytes, PI 3
      kinase feedback control of signalling by the insulin receptor and IRS proteins is
      multifaceted and reciprocal, illustrating the complexity of predicting the net
      flux of the insulin signal(s) through the IRS proteins.

PMID- 12220230
TI  - Leptin exists in tubuli seminiferi and in seminal plasma.
AB  - Leptin is a 167-amino acid protein that stimulates gonadotrophin-releasing
      hormone secretion and exerts indirect effects on the gonads via neuropeptide Y,
      NPY. Recent research has suggested that leptin may also have an effect on
      testosterone secretion. To investigate the role of leptin in reproduction, leptin
      in testicular tissue and seminal plasma was examined in relation to leptin in
      serum, semen sample qualities and vasectomy. Seminal plasma and serum of 64
      infertility patients, and 15 individuals after vasectomy, were assayed for leptin
      using a competitive 'in house' radioimmunoassay. The concentration of leptin in
      seminal plasma was significantly lower in the 'normal' semen sample group than in
      the 'pathological' group (Mean +/- SEM; 1.45 +/- 0.18 vs. 3.19 +/- 0.57 ng ml-1;
      P < 0.05), and showed a significantly negative correlation with percentage of
      motile spermatozoa (r = -0.46; P = 0.0005) and with the velocity straight line,
      VSL, (r = -0.30; P = 0.029). In contrast, leptin concentration in serum did not
      show any relationship with the spermiogram parameters. In testicular tissue,
      leptin was preferentially found within the tubuli seminiferi using anti-leptin
      polyclonal antibody, Ob A-20 Sc 842. The amount of leptin per ejaculate did not
      significantly change after vasectomy, and was not correlated to fructose, zinc or
      neutral alpha glucosidase in seminal plasma (P > 0.05). These results suggest
      that the amount of leptin in the genital tract, including the tubuli seminiferi,
      may influence the mechanisms involved in the motility development of spermatozoa.

PMID- 12220231
TI  - History of the microscope and development of microsurgery: a revolution for
      reproductive tract surgery.
AB  - In the mid-1970s urologists in the field of paediatric and andrologic surgery
      felt that operating loupes did not provide sufficient magnification for their
      surgical work. Thus, urology finally introduced the operating microscope in the
      operating room, which was rather late in comparison to other surgical
      disciplines. Almost three decades later we can hardly imagine performing a
      vasovasostomy, a testicular autotransplantation or a penile reconstruction
      without the use of this sophisticated instrument. The following article from the
      history of medicine reveals the main steps in the technical development of the
      microscope, from early magnifying tools to the pioneering inventions of Carl
      Zeiss (1816-1888) and his successful company in Jena, Germany in the 19th
      century. Finally, the clinical application of microsurgery in the 20th century is
      described, focusing on reconstruction of the reproductive tract in andrology and
      gynaecology.

PMID- 12220232
TI  - Effect of experimental varicocele in rats on testicular oxidative stress status.
AB  - The present experiments were undertaken to determine the levels of MDA, SOD and
      catalase in the testis of adolescent rats with experimental left varicoceles.
      Male Wistar rats, 7 weeks old and weighing 160-170 g, were randomly allocated
      into three groups. The first group of rats underwent partial ligation of the left
      renal vein (n = 15). The second group of rats underwent a sham operation (n = 7)
      and the third group acted as controls (n = 7). Animals were sacrificed 6 weeks
      after surgery and dilatation of the internal spermatic veins was observed. Levels
      of MDA, SOD and catalase activity were measured in testis. The experimental left
      varicocele group showed severe testicular changes compared to other groups. The
      mean MDA (SEM) levels in right and left testicular tissues of varicocele bearing
      rats, sham-operated rats, and control rats were 0.48 +/- 0.24 and 0.31 +/- 0.11,
      0.22 +/- 0.02 and 0.35 +/- 0.12, 0.62 +/- 0.29 and 0.13 +/- 0.05, respectively (P
      > 0.05). The mean SOD (SEM) levels in right and left testicular tissues of
      varicocele bearing rats, sham-operated rats, and control rats were 7,790 +/- 606
      and 6,974 +/- 574, 7,475 +/- 1,517 and 7020 +/- 1,106, 8,727 +/- 1,188 and 9,019
      +/- 1,129, respectively (P > 0.05). The mean catalase (SEM) levels in right and
      left testicular tissues of varicocele bearing rats,sham-operated rats, and
      control rats were 75.77 +/- 11.5 and 53.82 +/- 10.1, 91.94 +/- 14 and 94.90 +/-
      32, 65.40 +/- 5.7 and 90.93 +/- 16.4, respectively (P > 0.05). Our results
      suggest that oxidative status, which reflects a relative balance between reactive
      oxygen species (ROS) generated and ROS scavenged, may not be responsible for the
      testicular dysfunction associated with experimentally induced varicocele during
      adolescence in rats.

PMID- 12220233
TI  - Five years experiences with microinjection of testicular spermatozoa into oocytes
      in Hungary.
AB  - The aim of the study was to summarize our five years experience (1996-2000) of
      testicular spermatozoa for intracytoplasmic sperm injection in Hungary. The
      influence of sperm count, maternal age, number of transferred embryos, and
      application of assisted hatching on outcome was investigated. Testicular
      spermatozoa were retrieved by microsurgical testicular sperm extraction. Samples
      were classified depending on the number of spermatozoa. Indication for testicular
      sperm extraction in conjunction with intracytoplasmic sperm injection was severe
      azoospermia or azoospermia combined with tubal origin infertility. Ovarian
      stimulation was carried out using an ultrashort protocol with GnRH agonist and
      gonadotrophin. Intracytoplasmic sperm injection was performed without PVP.
      Embryos were cultured for 48 or 72 h before embryo transfer. Indications for
      assisted hatching included elevated maternal age, increased zona thickness or at
      least two previous unsuccessful IVF cycles. Testicular spermatozoa were
      successfully retrieved in 218 out of 273 cases. Extreme low sperm count was found
      more frequently in cases of nonobstructive azoospermia. No significant
      differences were observed in fertilization rate (61.1% vs. 51.7%) or clinical
      pregnancy rate (29.0% vs. 26.7%) between patients with obstructive or
      nonobstructive azoospermia. Maternal age, number of transferred embryos and
      application of assisted hatching had a significant effect on outcome. A total of
      55 clinical pregnancies were achieved, including 14 sets of twins, three sets of
      triplets and two sets of quadruplets. It is concluded that testicular sperm
      extraction is an efficient way of obtaining testicular spermatozoa, allowing not
      only successful fertilization by ICSI, but also freezing of testicular
      spermatozoa for use in subsequent cycles.

PMID- 12220234
TI  - Development of the blood-testis barrier in the mouse is delayed by neonatally
      administered diethylstilbestrol but not by beta-estradiol 3-benzoate.
AB  - A group of newborn mice were treated with 1 micro g dose-1 individual-1 of
      diethylstilbestrol (DES) on alternate days, from days 1 to 11 postnatally.
      Another group of mice were treated similarly with 125 ng dose-1 individual-1 of
      beta-estradiol 3-benzoate (E2B). The testes were sequentially examined up to 84
      days of age using light and electron microscopy. Spermatogenic cells in the DES
      treated mice differentiated normally from birth until 17 days of age, when they
      differentiated into pachytene spermatocytes and remained at this meiotic prophase
      for the next 10 days approximately. The cells then began to differentiate
      further, ultimately forming spermatozoa by 49 days of age. Confocal and electron
      microscopy showed that the blood-testis barrier did not form until 28 days of age
      in the DES-treated mice, and a delay in the functional maturation of this
      structure, as the blood-testis barrier, was confirmed by intercellular tracer
      experiments. The arrest of spermatogenesis at the meiotic prophase may have been
      attributable to the DES-induced defective formation of the blood-testis barrier.
      No delay of the blood-testis barrier formation was detected in the E2B-treated
      mice. Thus, DES and E2B, both of which are known as potent oestrogenic compounds,
      had different effects on the Sertoli cells.

PMID- 12220239
TI  - The role of new diagnostic tests in transplant infectious disease.

PMID- 12220240
TI  - Persistent lack of human herpesvirus-6 specific T-helper cell response in liver
      transplant recipients.
AB  - BACKGROUND: Specific immunologic defects predisposing to human herpesvirus-6 (HHV
      6), e.g. the role of HHV-6 specific T-helper cell memory response in liver
      transplant recipients, have not been assessed. METHODS: T-helper function
      (mitogen ConA response) as a marker of overall immunocompetence and T-helper
      response (memory response) specific to HHV-6 and cytomegalovirus (CMV) were
      assessed in 15 liver transplant recipients and compared with 25 healthy subjects.
      Samples were tested pretransplant, at 2 weeks, 1 month, 2-3 months, and 1 year
      posttransplantation. Stimulation index (SI) >3 was considered a positive
      response. RESULTS: Seven percent (1/15) of the transplant recipients at any time
      posttransplantation, as compared to 64% (16/25) of the healthy subjects, had a
      positive HHV-6 memory response (P = 0.00065). HHV-6-specific memory response in
      transplant recipients at 2 weeks (SI 1.43), 1 month (SI 1.1), and 2-3 months (SI
      1.3) was significantly more suppressed than in healthy subjects (SI 17.5, P =
      0.0001). Although transplant recipients as compared to healthy subjects also had
      a lower CMV-specific memory response posttransplant (P = 0.0439), CMV-specific
      memory response recovered significantly at 1 month (P = 0.03) and at 2-3 months
      (P = 0.027) as compared to that at 2 weeks. However, HHV-6 memory response was
      persistently absent up to 2-3 months with partial recovery at 1 year; 7% of the
      patients at 2-3 months, but 25% at 1 year had a positive HHV-6 specific memory
      response. Forty percent (6/15) of the patients developed HHV-6 viremia a mean of
      4 weeks posttransplant. Patients with HHV-6 viremia had greater suppression of
      HHV-6 memory response at 1 month than those without viremia (mean SI, 0.96 vs.
      1.3, P = 0.08). All but one of the patients had a positive ConA response.
      CONCLUSION: Prolonged suppression of HHV-6 memory response, but not overall T
      helper cell function was documented and may play a role in the pathogenesis of
      HHV-6 infection in liver transplant recipients. Memory response to CMV after
      liver transplantation was significantly more robust than to HHV-6.

PMID- 12220241
TI  - Aspergillus galactomannan antigen levels in allogeneic haematopoietic stem cell
      transplant recipients given total parenteral nutrition.
AB  - False-positive tests for Aspergillus galactomannan have been reported in
      neutropenic patients. We failed to detect any circulating antigen during the 2
      weeks following allogeneic haematopoietic stem cell transplantation of 12
      patients who had severe mucositis but were unable to eat.

PMID- 12220242
TI  - Aerosolized pentamidine prophylaxis for Pneumocystis carinii pneumonia after
      allogeneic marrow transplantation.
AB  - Pneumocystis carinii pneumonia (PCP) poses a serious risk to allogeneic bone
      marrow transplant (BMT) patients, who are often intolerant of trimethoprim
      sulfamethoxazole (TMP-SMX), the traditional first-line prophylactic agents. There
      are limited published data supporting the use of aerosolized pentamidine (AP)
      prophylaxis in the BMT population. We assessed the effectiveness of AP in BMT
      recipients by reviewing the experience at our center. We divided our review into
      four time periods from January 1990 to March 2000, during which approximately 700
      BMTs were performed. The first period includes patients receiving AP treatments
      from January 1990 to July 1997 (baseline), the second from August 1997 to July
      1998 (pre-outbreak), the third from August 1998 to October 1999 (outbreak), and
      the fourth from November 1999 to March 2000 (post-outbreak). At our center, TMP
      SMX is the first-line agent for PCP prophylaxis, which is routinely continued for
      at least one year, or for the duration of enhanced immunosuppression. During the
      baseline period, 505 BMTs were performed and 192 patients (38%) received AP for
      part of their time at risk. Six patients (3%) experienced toxicities requiring
      discontinuation of AP. Three cases of PCP were diagnosed over 1114 patient-months
      of treatment in the baseline period. During the last 42 months of the baseline
      period, 2/154 patients receiving AP and 2 of an estimated 293 patients receiving
      exclusively oral prophylaxis developed breakthrough PCP (p = 0.61). During the
      outbreak period, 9 of 180 patients receiving AP developed PCP compared to none in
      the group receiving exclusively oral prophylaxis. Either changes in our AP
      protocol during the pre-outbreak period or pentamidine resistance may have led to
      this failure of prophylaxis. There were no further cases during the 5-month post
      outbreak period. Our observed overall breakthrough rate was 12 cases out of 439
      patients (2.7%). Our study shows that AP is an effective and well-tolerated
      second-line agent in preventing PCP post BMT and we recommend its continued use
      in this regard. However, it should be administered using a well-studied protocol,
      and only when TMP-SMX is not tolerated.

PMID- 12220243
TI  - CMV retinitis after allogeneic bone marrow transplantation: a report of five
      cases.
AB  - Four cases of cytomegalovirus (CMV) retinitis (CMVR) after allogeneic blood stem
      cell transplant (SCT) were documented in Huddinge University Hospital between
      1994 and 1999. Prior to 1994, only one case was documented. All five patients
      were transplanted due to malignant disease, two with sibling donors and three
      with matched unrelated donors. Despite adequate antiviral treatment against CMV
      retinitis, the result has been almost total unilateral blindness in three
      patients. However rare, the complication seems to have become more common since
      we began doing more matched unrelated donor transplants, which leads to a more
      pronounced T-cell defect and to a delayed immune reconstitution compared to
      sibling transplants. We conclude that CMV retinitis is a rare but important
      complication to allogeneic blood stem cell transplantation.

PMID- 12220244
TI  - Open lung biopsy in bone marrow transplant recipients has a poor diagnostic yield
      for a specific diagnosis.
AB  - The diagnostic yield of open lung biopsy (OLB) in bone marrow transplantation
      (BMT) recipients having pulmonary infiltrates has not been evaluated recently.
      Therefore, we reviewed our 2-year experience (1998-99) with such patients at The
      University of Texas M. D. Anderson Cancer Center. We found 12 BMT recipients who
      underwent OLB analysis for the evaluation of pulmonary infiltrates. A treatable
      infectious etiology leading to the initiation or modification of antimicrobial
      agent administration was found in only two patients having bilateral nodular
      disease and one having bilateral parenchymal infiltrates. We conclude that OLB in
      BMT patients having diffuse pulmonary infiltrates has a low diagnostic yield for
      treatable infectious etiologies.

PMID- 12220245
TI  - Immunopathogenesis of hepatitis C virus in the immunosuppressed host.
AB  - The prevalence of chronic hepatitis C virus (HCV) infection among various groups
      of immunosuppressed patients is high. These groups include patients co-infected
      with human immunodeficiency virus (HIV), recipients of organ transplants, and
      those with hypogammaglobulinemia. The liver disease in the immunosuppressed host
      is typically severe with an unusually rapid progression to cirrhosis. This is
      somewhat paradoxical, as the classical model for HCV-induced liver disease
      assumes that cell-mediated immune responses induce liver injury. It is likely
      that a combination of viral-related factors and host-related factors plays a role
      in this accelerated natural history of HCV. Data are accumulating in
      immunocompromised hosts that address the immunopathogenesis of liver injury,
      although there are still fundamental gaps in our understanding of this process.
      In this review, we will focus on our current understanding of the mechanisms of
      liver injury and how it relates to the accelerated liver disease progression in
      immunocompromised hosts.

PMID- 12220246
TI  - Toxoplasma gondii pneumonia in liver transplantation: survival after a severe
      case of reactivation.
AB  - Toxoplasmosis is an infrequent infection in solid organ transplantation, except
      in heart transplantation, where the grafting of a positive organ in a negative
      recipient transmits the infection in a high percentage of cases, in the absence
      of prophylaxis. We report a case of pneumonia by Toxoplasma gondii in a woman who
      received a liver transplant and had pre-transplant positive serology. Diagnosis
      was made by cytologic examination of bronchoalveolar lavage fluid, where the
      parasite was observed with hematoxylin-eosin and Giemsa staining. That finding
      was confirmed by direct immunofluorescence and positive polymerase chain
      reaction. The patient had a favorable outcome, although she had not initially
      received first-choice drugs. This was a case of severe illness secondary to
      reactivation of Toxoplasma infection, diagnosed pre-mortem and with a favorable
      outcome. Duration of treatment and need for secondary prophylaxis in these
      patients are discussed in the literature. Although infrequent, toxoplasmosis must
      be considered among the differential diagnoses of pulmonary infiltrates in solid
      organ transplantation.

PMID- 12220247
TI  - Human granulocytic ehrlichiosis in a renal allograft recipient: review of the
      clinical spectrum of disease in solid organ transplant patients.
AB  - BACKGROUND: Ehrlichiosis is a recently described zoonotic infection with two
      major expressions: human granulocytic ehrlichiosis (HGE) and human monocytic
      ehrlichiosis (HME). The organisms associated with HGE and HME have been detected
      in a tick vector in several regions of United States and cases of ehrlichiosis
      have been reported in the general population. METHODS: We report a case of HGE in
      a renal allograft recipient and review the clinical spectrum of disease in solid
      organ transplant recipients and the epidemiological basis for risk. RESULTS: Our
      patient demonstrated the typical epidemiological, clinical and laboratory
      features of human granulocytic ehrlichiosis and responded to treatment with
      doxycycline. CONCLUSIONS: Human ehrlichiosis should be considered in the
      differential diagnosis of patients with solid organ transplants, who present with
      fever and thrombocytopenia. The incidence of ehrlichiosis in the solid organ
      transplant population is similar to that in the United States general population.
      As reported in immunocompetent patients, prompt diagnosis and treatment results
      in the rapid resolution of symptoms in transplanted individuals.

PMID- 12220248
TI  - Disseminated microsporidiosis in a renal transplant recipient.
AB  - Disseminated microsporidiosis is diagnosed uncommonly in patients not infected
      with human immunodeficiency virus (HIV). We present a case of disseminated
      microsporidiosis in a renal transplant recipient who was seronegative for HIV.
      Chromotrope-based stains were positive for microsporidia in urine, stools,
      sputum, and conjunctival scrapings. Electron microscopy, immunofluorescence,
      polymerase chain reaction, and cultures of renal tissue identified the organism
      as Encephalitozoon cuniculi. The patient was treated with oral albendazole and
      topical fumagillin with clinical improvement. In addition, she underwent a
      transplant nephrectomy and immunosuppressive therapy was withdrawn. Follow-up
      samples were negative for microsporidia. However, the patient developed central
      nervous system manifestations and died. An autopsy brain tissue specimen
      demonstrated E. cuniculi by immunofluorescent staining. Disseminated
      microsporidiosis must be considered in the differential diagnosis of multiorgan
      involvement in renal allograft recipients.

PMID- 12220249
TI  - Intracranial Nocardia dissemination during minocycline therapy.
AB  - Nocardia species is a well-known pathogen in immunocompromised hosts, including
      renal transplant recipients. Primary pulmonary infection can disseminate to other
      organs and recommended first-line therapy is high-dose
      trimethoprim/sulfamethoxazole (TMP/SMX). We report two cases of primary pulmonary
      Nocardia sp. in immunosuppressed patients who were treated with minocycline, a
      second-line drug. During treatment with minocycline, both patients developed
      central nervous system (CNS) lesions of Nocardia sp. and were then treated with
      TMP/SMX with resolution of disease. The literature on Nocardia and treatment with
      minocycline is reviewed. Treatment of pulmonary Nocardia sp. with 200 mg
      minocycline daily is not adequate to prevent disseminated CNS disease.

PMID- 12220250
TI  - A fatal case of hepatitis C seroconversion following living related kidney
      transplantation: another argument for nucleic acid amplification testing of
      transplant recipients and donors.

PMID- 12220251
TI  - Genome detection and transfusion: setting the scene.

PMID- 12220252
TI  - Nucleic acid amplification technology methods used in blood donor screening.

PMID- 12220253
TI  - US NAT yield: where are we after 2 years?
AB  - The US blood supply has been tested for human immunodeficiency virus-1 (HIV-1)
      and hepatitis C virus (HCV) using nucleic acid amplification testing (NAT) of
      pools of small number of samples since early 1999. Since the implementation of
      NAT under an investigational new drug (IND) application, the results for the
      yield and false positivity have been remarkably consistent for greater than 2
      years of testing even among multiple programmes using two different test
      methodologies and manufacturers: Gen-Probe/Chiron transcription-mediated
      amplification (TMA) and Roche polymerase chain reaction. All programmes in the US
      and Canada use NAT as a criterion for cellular as well as frozen product release.
      The focus of this paper is to provide an update of the programmes in the US and
      Canada, provide data in support of p24 antigen replacement by HIV-1 NAT and
      discuss the projections of residual risk of HIV, HCV and hepatitis B virus (HBV)
      following NAT and the associated cost/benefit.

PMID- 12220254
TI  - The German experience with NAT.

PMID- 12220255
TI  - Scottish experience with NAT.

PMID- 12220256
TI  - Implementation of genome amplification technology for HCV RNA detection.

PMID- 12220257
TI  - Nucleic acid testing for emerging viral infections.
AB  - The development of new technologies leads to the discovery of new viruses. For
      each of these new infectious agents, relevance to transfusion, including
      transmissibility by transfusion, pathogenicity, prevalence in blood donors,
      persistence and the availability of screening assays needs to be assessed. Since
      1995, one virus and a new family of viruses have been identified. GB virus
      C/hepatitis G virus (GBV-C/HGV), a flavi virus with some homology with and
      epidemiological features of HCV, is not related to post-transfusion hepatitis but
      seems to positively interfere with human immunodeficiency virus replication.
      Human circoviruses include TT virus (TTV) and SEN-V. Both are highly variable,
      constituting a large family of distantly related viruses. They appear ubiquitous,
      infecting humans very early in life and are largely persistent. No clinical
      symptoms or pathogenicity is associated with TTV, but SEN-V might be associated
      with some non-A-E post-transfusion hepatitis. Parvovirus B19 has been known for
      many years, but its transmission to recipients of plasma derivatives despite
      viral inactivation raised the issue of screening plasma pools by nucleic acid
      testing. Most fractionators quantify B19 DNA in plasma pools to ensure a viral
      load of <10(4) IU mL-1.

PMID- 12220260
TI  - Environmental and auxin regulation of wood formation involves members of the
      Aux/IAA gene family in hybrid aspen.
AB  - Indole acetic acid (IAA/auxin) profoundly affects wood formation but the
      molecular mechanism of auxin action in this process remains poorly understood. We
      have cloned cDNAs for eight members of the Aux/IAA gene family from hybrid aspen
      (Populus tremula L. x Populus tremuloides Michx.) that encode potential mediators
      of the auxin signal transduction pathway. These genes designated as PttIAA1
      PttIAA8 are auxin inducible but differ in their requirement of de novo protein
      synthesis for auxin induction. The auxin induction of the PttIAA genes is also
      developmentally controlled as evidenced by the loss of their auxin inducibility
      during leaf maturation. The PttIAA genes are differentially expressed in the cell
      types of a developmental gradient comprising the wood-forming tissues.
      Interestingly, the expression of the PttIAA genes is downregulated during
      transition of the active cambium into dormancy, a process in which meristematic
      cells of the cambium lose their sensitivity to auxin. Auxin-regulated
      developmental reprogramming of wood formation during the induction of tension
      wood is accompanied by changes in the expression of PttIAA genes. The distinct
      tissue-specific expression patterns of the auxin inducible PttIAA genes in the
      cambial region together with the change in expression during dormancy transition
      and tension wood formation suggest a role for these genes in mediating cambial
      responses to auxin and xylem development.

PMID- 12220261
TI  - A dominant nuclear mutation in Chlamydomonas identifies a factor controlling
      chloroplast mRNA stability by acting on the coding region of the atpA transcript.
AB  - We have characterized a nuclear mutation, mda1-ncc1, that affects mRNA stability
      for the atpA gene cluster in the chloroplast of Chlamydomonas. Unlike all nuclear
      mutations altering chloroplast gene expression described to date, mda1-ncc1 is a
      dominant mutation that still allows accumulation of detectable amounts of atpA
      mRNAs. At variance with the subset of these mutations that affect mRNA stability
      through the 5' UTR of a single chloroplast transcript, the mutated version of
      MDA1 acts on the coding region of the atpA message. We discuss the action of MDA1
      in relation to the unusual pattern of expression of atpA that associates
      particularly short lived-transcripts with a very high translational efficiency.

PMID- 12220262
TI  - Does proline accumulation play an active role in stress-induced growth reduction?
AB  - An interesting observation, reported for transgenic plants that have been
      engineered to overproduce osmolytes, is that they often exhibit impaired growth
      in the absence of stress. As growth reduction and accumulation of osmolytes both
      typically result from adaptation, we hypothesized that growth reduction may
      actually result from osmolyte accumulation. To examine this possibility more
      closely, intracellular proline level was manipulated by expressing mutated
      derivatives of tomPRO2 (a Delta(1)-pyrroline-5-carboxylate synthetase, P5CS, from
      tomato) in Saccharomyces cerevisiae. This was done in the presence and absence of
      a functional proline oxidase, followed by selection and screening for increased
      accumulation of proline in the absence of any stress. Here we show, in support of
      our hypothesis, that the level of proline accumulation and the amount of growth
      are inversely correlated in cells grown under normal osmotic conditions. In
      addition, the intracellular concentration of proline also resulted in increases
      in ploidy level, vacuolation and altered accumulation of several different
      transcripts related to cell division and gene expression control. Because these
      cellular modifications are common responses to salt stress in both yeast and
      plants, we propose that proline and other osmolytes may act as a
      signaling/regulatory molecule able to activate multiple responses that are part
      of the adaptation process. As in previous studies with transgenic plants that
      overaccumulate osmolytes, we observed some increase in relative growth of proline
      overaccumulating cells in mild hyperosmotic stress.

PMID- 12220263
TI  - GLK gene pairs regulate chloroplast development in diverse plant species.
AB  - Chloroplast biogenesis is a complex process that requires close co-ordination
      between two genomes. Many of the proteins that accumulate in the chloroplast are
      encoded by the nuclear genome, and the developmental transition from proplastid
      to chloroplast is regulated by nuclear genes. Here we show that a pair of Golden
      2-like (GLK) genes regulates chloroplast development in Arabidopsis. The GLK
      proteins are members of the GARP superfamily of transcription factors, and
      phylogenetic analysis demonstrates that the maize, rice and Arabidopsis GLK gene
      pairs comprise a distinct group within the GARP superfamily. Further phylogenetic
      analysis suggests that the gene pairs arose through separate duplication events
      in the monocot and dicot lineages. As in rice, AtGLK1 and AtGLK2 are expressed in
      partially overlapping domains in photosynthetic tissue. Insertion mutants
      demonstrate that this expression pattern reflects a degree of functional
      redundancy as single mutants display normal phenotypes in most photosynthetic
      tissues. However, double mutants are pale green in all photosynthetic tissues and
      chloroplasts exhibit a reduction in granal thylakoids. Products of several genes
      involved in light harvesting also accumulate at reduced levels in double mutant
      chloroplasts. GLK genes therefore regulate chloroplast development in diverse
      plant species.

PMID- 12220264
TI  - Flux control of sulphate assimilation in Arabidopsis thaliana: adenosine 5'
      phosphosulphate reductase is more susceptible than ATP sulphurylase to negative
      control by thiols.
AB  - The effect of externally applied L-cysteine and glutathione (GSH) on ATP
      sulphurylase and adenosine 5'-phosphosulphate reductase (APR), two key enzymes of
      assimilatory sulphate reduction, was examined in Arabidopsis thaliana root
      cultures. Addition of increasing L-cysteine to the nutrient solution increased
      internal cysteine, gamma-glutamylcysteine and GSH concentrations, and decreased
      APR mRNA, protein and extractable activity. An effect on APR could already be
      detected at 0.2 mm L-cysteine, whereas ATP sulphurylase was significantly
      affected only at 2 mm L-cysteine. APR mRNA, protein and activity were also
      decreased by GSH at 0.2 mm and higher concentrations. In the presence of L
      buthionine-S, R-sulphoximine (BSO), an inhibitor of GSH synthesis, 0.2 mm L
      cysteine had no effect on APR activity, indicating that GSH formed from cysteine
      was the regulating substance. Simultaneous addition of BSO and 0.5 mm GSH to the
      culture medium decreased APR mRNA, enzyme protein and activity. ATP sulphurylase
      activity was not affected by this treatment. Tracer experiments using (35)SO(4)(2
      ) in the presence of 0.5 mm L-cysteine or GSH showed that both thiols decreased
      sulphate uptake, APR activity and the flux of label into cysteine, GSH and
      protein, but had no effect on the activity of all other enzymes of assimilatory
      sulphate reduction and serine acetyltransferase. These results are consistent
      with the hypothesis that thiols regulate the flux through sulphate assimilation
      at the uptake and the APR step. Analysis of radioactive labelling indicates that
      the flux control coefficient of APR is more than 0.5 for the intracellular
      pathway of sulphate assimilation. This analysis also shows that the uptake of
      external sulphate is inhibited by GSH to a greater extent than the flux through
      the pathway, and that the flux control coefficient of APR for the pathway,
      including the transport step, is proportionately less, with a significant share
      of the control exerted by the transport step.

PMID- 12220265
TI  - Light regulated modulation of Z-box containing promoters by photoreceptors and
      downstream regulatory components, COP1 and HY5, in Arabidopsis.
AB  - The Z-box is one of the light-responsive elements (LREs) found in the promoters
      of light inducible genes. We have studied the light responsive characteristics of
      Z-box containing synthetic as well as native promoters. We show that promoters
      with Z-box as a single LRE or paired with another LRE can respond to a broad
      spectrum of light. The response is primarily mediated by phyA, phyB and CRY1
      photoreceptors at their respective wavelengths of light. We have demonstrated
      that CAB1 and Z-GATA containing promoters are down-regulated in hy5 mutants in
      the light. On the other hand, a promoter with Z-box alone is down-regulated in
      hy5 mutants both in dark and in light conditions, suggesting involvement of a
      similar regulatory system in the regulation of the promoter in two distinct
      developmental pathways: skotomorphogenesis and photomorphogenesis. Furthermore,
      similar to the CAB1 promoter, a Z-GATA containing promoter is derepressed in cop1
      mutants in the dark. DNA-protein interaction studies reveal the presence of a DNA
      binding activity that is specific to Z-box. These results provide insights into
      the regulation of the Z-box LRE mediated by various light signaling components.

PMID- 12220266
TI  - Isolation, cloning and expression of a multifunctional O-methyltransferase
      capable of forming 2,5-dimethyl-4-methoxy-3(2H)-furanone, one of the key aroma
      compounds in strawberry fruits.
AB  - Strawberry fruits contain an uncommon group of key aroma compounds with a 2,5
      dimethyl-3(2H)-furanone structure. Here, we report on the methylation of 2,5
      dimethyl-4-hydroxy-3(2H)-furanone (DMHF) to 2,5-dimethyl-4-methoxy-3(2H)-furanone
      (DMMF) by a S-adenosyl-L-methionine dependent O-methyltransferase, the cloning of
      the corresponding cDNA and characterization of the encoded protein. Northern
      hybridization indicated that the Strawberry-OMT specific transcripts accumulated
      during ripening in strawberry fruits and were absent in root, petiole, leaf and
      flower. The protein was functionally expressed in E. coli and exhibited a
      substrate specificity for catechol, caffeic acid, protocatechuic aldehyde,
      caffeoyl CoA and DMHF. A common structural feature of the accepted substrates was
      a o-diphenolic structure also present in DMHF in its dienolic tautomer. FaOMT is
      active as a homodimer and the native enzyme shows optimum activity at pH 8.5 and
      37 degrees C. It does not require a cofactor for enzymatic activity. Due to the
      expression pattern of FaOMT and the enzymatic activity in the different stages of
      fruit ripening we suppose that FaOMT is involved in lignification of the achenes
      and the vascular bundles in the expanding fruit. In addition, it is concluded
      that the Strawberry-OMT plays an important role in the biosynthesis of strawberry
      volatiles such as vanillin and DMMF.

PMID- 12220267
TI  - In planta protein-protein interactions assessed using a nanovirus-based
      replication and expression system.
AB  - The multipartite genome of the nanovirus Faba bean necrotic yellows virus, which
      consists of one gene on each DNA component, was exploited to construct a series
      of virus-based episomal vectors designed for transient replication and gene
      expression in plants. This nanovirus based expression system yields high levels
      of protein which allows isolation of recombinant protein and protein complexes
      from plant tissues. As examples, we demonstrated in planta interaction between
      the nanovirus F-box protein Clink and SKP1, a constituent of the ubiquitin
      dependent protein turnover pathway. Thus, replicative nanovirus vectors provide a
      simple and efficient means for in planta characterization of protein-protein
      interaction.

PMID- 12220268
TI  - Virus-induced gene silencing in tomato.
AB  - We have previously demonstrated that a tobacco rattle virus (TRV)-based vector
      can be used in virus-induced gene silencing (VIGS) to study gene function in
      Nicotiana benthamiana. Here we show that recombinant TRV infects tomato plants
      and induces efficient gene silencing. Using this system, we suppressed the PDS,
      CTR1 and CTR2 genes in tomato. Suppression of CTR1 led to a constitutive ethylene
      response phenotype and up-regulation of an ethylene response gene, CHITINASE B.
      This phenotype is similar to Arabidopsis ctr1 mutant plants. We have constructed
      a modified TRV vector based on the GATEWAY recombination system, allowing
      restriction- and ligation-free cloning. Our results show that tomato expressed
      sequence tags (ESTs) can easily be cloned into this modified vector using a
      single set of primers. Using this vector, we have silenced RbcS and an endogenous
      gene homologous to the tomato EST cLED3L14. In the future, this modified vector
      system will facilitate large-scale functional analysis of tomato ESTs.

PMID- 12220269
TI  - Erythrokeratodermia variabilis with erythema gyratum repens-like lesions.
AB  - A large pedigree with erythrokeratodermia variabilis (EKV) and erythema gyratum
      repens-like lesions is described. Clinical, laboratory, and histologic findings
      of this family are presented. The differential diagnoses of the following
      dermatoses with an erythematous and a hyperkeratotic component are discussed:
      erythrokeratodermia variabilis (Mendes da Costa), progressive symmetric
      erythrokeratoderma (Gottron), loricrin keratoderma, erythrokeratoderma en
      cocardes (Degos), Netherton syndrome, keratitis-ichthyosis-deafness (KID)
      syndrome, erythrokeratolysis hiemalis (Oudtshoorn disease), and nonbullous
      congenital ichthyosiform erythroderma.

PMID- 12220270
TI  - Congenital nevocytic nevi: follow-up of a Swedish birth register sample regarding
      etiologic factors, discomfort, and removal rate.
AB  - Congenital nevi both small and large are frequently removed. We attempted to
      study the removal rate and etiologic aspects of congenital nevi as well as their
      psychosocial effects through the use of a quality test. A questionnaire sent to a
      sample population of individuals with congenital nevocytic nevi (n=192) collected
      from the Swedish Medical Birth Register (SMBR) was used as a test of the
      register's quality and for collecting information on rate of removal and
      etiologic factors. The quality test indicated that only 85.3% of the nevi listed
      in the SMBR were true congenital nevocytic nevi. Of all true congenital nevocytic
      nevi reported in the questionnaire, 39.8% had been removed and none of the rest
      had developed malignant melanoma. The median time for follow-up was 14 years. The
      median age at removal of the nevi was 9.7 years. Eight percent of respondents
      believed that the skin lesion caused taunting and changed their social
      activities. No infection or illness during pregnancy was specifically related to
      the development of congenital nevi. In conclusion, the larger the nevi, the more
      frequently and earlier they are excised. With an excision rate of 40% of
      congenital nevocytic nevi, we found no malignant melanoma.

PMID- 12220271
TI  - A clinical study of childhood alopecia areata in Singapore.
AB  - Alopecia areata (AA) is a common cause of nonscarring alopecia. The aim of this
      epidemiologic study is to review the clinical characteristics and treatment of
      childhood alopecia areata in a mixed ethnic population. The study population
      consisted of a total of 392 children seen over a 4-year period with AA diagnosed
      before the age of 16 years. The female:male ratio was 1:1.4. There were 309
      Chinese (78.8%), 51 Malays (13.0%), and 32 Indians (8.2%). The mean age at the
      time of diagnosis was 11.2 years. The majority of patients (71.7%) had alopecia
      of less than 6-months duration and 6% had previous episodes of AA. Females
      appeared to have more severe involvement. A familial history of AA was observed
      in 33 patients (8.4%). Associated atopy was found in 26.6% of patients and in
      32.3% of their first-degree relatives. Other associations such as vitiligo or
      Down syndrome were rare. For limited AA, topical and/or intralesional
      corticosteroid was the first-line treatment used and squaric acid dibutyl ester
      was the choice of treatment for patients with extensive involvement. The profile
      of the poor respondents to therapy included young age of onset, past history of
      AA, Down syndrome, and extensive involvement.

PMID- 12220272
TI  - Cole disease: hypopigmentation with punctate keratosis of the palms and soles.
AB  - Cole disease is an uncommon disorder characterized by distinctive cutaneous
      hypopigmentation and punctate keratosis of the palms and soles. It is a
      congenital skin disease with an autosomal dominant inheritance pattern. We report
      two patients from a family with 15 members, 5 of whom were affected. One of the
      patients had both types of lesions since birth, while in the other they arose in
      the first months of life. We studied the pedigree, histopathology,
      immunohistochemistry, and electron microscopy findings of the hypopigmented
      macules with the patients' normal skin used as a control. The pedigree showed
      involvement of both genders, with a Mendelian autosomal dominant inheritance
      pattern with phenotypic variability in the family. Immunohistochemistry showed a
      reduction in the melanin pigment in the keratinocytes and normal pigmentation in
      the melanocytes. Ultrastructural studies showed a strong contrast between the
      large number of melanosomes in the body and dendrites of the melanocytes, in
      contrast with the small number of these organelles in the neighboring
      keratinocytes. These findings suggest that this disease is a primary congenital
      disorder of the transfer mechanisms of the melanosomes from melanocytes to
      keratinocytes in hypopigmented lesions, associated with abnormal epidermopoiesis
      in the punctate hyperkeratosis.

PMID- 12220273
TI  - Prevalence of skin conditions in primary school children in Turkey: differences
      based on socioeconomic factors.
AB  - Skin diseases are associated with environmental factors and a public health
      approach is particularly important. We determined the prevalence of skin
      conditions and associated socioeconomic factors in primary school children in
      Turkey. A questionnaire for determining the socioeconomic level and a complete
      dermatologic examination were performed in 785 children in two primary schools in
      different socioeconomic areas of suburban and central Manisa, Turkey. The study
      included 345 (43.9%) girls and 440 (56.1%) boys with a mean age of 9.25 +/- 1.55
      (range 6-14 years). Infectious skin diseases were frequently observed:
      pediculosis capitis in 74 children (9.4%), scabies in 17 (2.2%), viral skin
      diseases in 30 (3.8%), and fungal infections in 6 (0.7%). The other common
      conditions were melanocytic nevi (14.4%), keratosis pilaris (12.5%), pityriasis
      alba (12%), xerosis (11.8%), and atopic dermatitis (6.8%). Pediculosis capitis,
      acne, and dandruff were more common in girls. The rate of infections, atopic
      dermatitis, xerosis, and pityriasis alba were significantly higher in the school
      children with poor socioeconomic conditions. Improvement in socioeconomic
      conditions along with education may be needed to decrease the prevalence of some
      of these skin disorders in order to decrease costs related to treatment.

PMID- 12220274
TI  - Rothmund-thomson syndrome in three siblings and development of cutaneous squamous
      cell carcinoma.
AB  - Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive genodermatosis. It
      is characterized by early onset of progressive poikiloderma and several other
      cutaneous and extracutaneous findings including alopecia, dystrophic teeth and
      nails, juvenile cataracts, short stature, hypogonadism, and bone defects. There
      are several reported cases of skin malignancies in RTS patients, indicating a
      possibly higher incidence of cutaneous and noncutaneous malignancies. We report
      three siblings with RTS who developed cutaneous squamous cell carcinoma (SCC).

PMID- 12220275
TI  - Pustular miliaria rubra: a specific cutaneous finding of type I
      pseudohypoaldosteronism.
AB  - Type I pseudohypoaldosteronism, an autosomal recessive, life-threatening disorder
      of mineralocorticoid resistance leads to excessive loss of sodium chloride
      through eccrine and other secretions. Recurrent episodes of pustular miliaria
      rubra are associated with salt-losing crises and clear spontaneously with
      stabilization. Inflammation of and around the damaged eccrine glands has been
      attributed to the deleterious effects of excessive eccrine gland salt exposure.

PMID- 12220276
TI  - Acrokeratoelastoidosis.
AB  - Acrokeratoelastoidosis of Costa is a rare papular palmoplantar keratosis
      characterized by small round-oval to rhomboid-shaped, yellowish papules most
      commonly localized to the palmar surface of the hands and sometimes also found on
      plantar surfaces of the feet. Both autosomal dominant and sporadic forms of the
      disease have been reported. Histologically acrokeratoelastoidosis is marked by
      hyperkeratosis and epidermal hypertrophy. Specific stains for elastic tissue
      reveal characteristic fragmentation and rarefaction of elastic fibers. We report
      a sporadic case of acrokeratoelastoidosis in a 13-year-old girl and review the
      etiology, differential diagnosis, and treatment of this disorder.

PMID- 12220277
TI  - Scrofuloderma after BCG vaccination.
AB  - A 7-month-old boy with scrofuloderma following BCG vaccination is presented. He
      had a 2 cm x 1 cm erythematous lesion with a sinus tract in the right cervical
      area. In addition, he had ulcerated erythematous lesions 0.5 cm x 0.5 cm in size
      on the left deltoid area and left forearm where BCG vaccination and a PPD test
      were performed, respectively. Histopathologic findings were consistent with the
      clinical diagnosis.

PMID- 12220278
TI  - Aplasia cutis congenita of the trunk with fetus papyraceus.
AB  - Aplasia cutis congenita (ACC) is the absence of localized or widespread areas of
      skin at birth. A frequently cited classification schema is based on location and
      the presence of associated anomalies. Histologically it is characterized by
      dermal fibrosis and absence of adenexal structures. We present a newborn female
      with extensive truncal ACC associated with fetus papyraceus.

PMID- 12220280
TI  - Congenital insensitivity to pain in four related Saudi families.
AB  - Congenital insensitivity to pain (hereditary sensory and autonomic neuropathy
      [HSAN] type V) is a rare disorder of pain perception in which pain sensation is
      absent from birth, with no other neurologic deficits. We report five Saudi
      patients (three male and two female) age 10 months to 23 years who lacked pain
      sensation from birth but have normal appreciation of other sensory modalities.
      They are from four related families who are descended from one grandfather. The
      patients had sustained many painless injuries resulting in fractures and
      disfigurement, but otherwise are completely normal.

PMID- 12220279
TI  - Ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC): report of a case with
      perioral papillomatosis.
AB  - We report a 13-year-old boy with ectodermal dysplasia, ectrodactyly, and
      syndactyly, hypospadias, photophobia, conductive hearing loss, and perioral
      papillomatosis. His father had ectrodactyly and hypotrichosis. The clinical
      picture suggested ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome. The
      presence of perioral papillomatosis, classically seen in Goltz syndrome, has been
      reported only once before in EEC syndrome.

PMID- 12220281
TI  - Dermatitis herpetiformis: should direct immunofluorescence be the only diagnostic
      criterion?
AB  - We describe a 7-year-old boy with dermatitis herpetiformis (DH) diagnosed on
      clinical and histologic evidence, negative direct immunofluorescence (DIF)
      findings for junctional IgA deposits in uninvolved skin, positive IgA endomysial
      and gliadin antibodies, and jejunal biopsy revealing a gluten-sensitive
      enteropathy. Treatment with dapsone led to the disappearance of cutaneous lesions
      and pruritus within 48 hours. Demonstration of IgA immune deposits in the dermal
      papillae has been the only acceptable criterion for the diagnosis of dermatitis
      herpetiformis. However, considering several reports in the literature of DH with
      a negative DIF and our own case, we believe that in the absence of the
      characteristic DIF pattern, one needs the combination of clinical, histologic,
      and immunologic data to support the diagnosis of DH. We also discuss recent
      developments in the diagnosis of DH.

PMID- 12220282
TI  - Successful surgical excision of a complex vascular lesion in an infant with
      Kasabach-Merritt syndrome.
AB  - Kasabach-Merritt syndrome, the association of a vascular lesion and consumptive
      coagulopathy, can represent a diagnostic and therapeutic challenge to clinicians.
      We describe an infant with a large complex vascular lesion of the left forearm
      that was successfully surgically excised. We propose surgical excision as an
      appropriate therapeutic option for some cases of Kasabach-Merritt syndrome.

PMID- 12220283
TI  - Netherton syndrome associated with idiopathic congenital hemihypertrophy.
AB  - Netherton syndrome is a rare genodermatosis comprised of anichthyosiform
      dermatitis, hair shaft defects, and atopic features. Other problems associated
      with Netherton syndrome are delayed growth and development, immune abnormalities,
      recurrent infections, and intermittent aminoaciduria. We describe an 18-month-old
      girl with Netherton syndrome who had idiopathic congenital hemihypertrophy on her
      right side with contralateral benign nephromegaly in addition to the
      characteristic clinical signs of the syndrome. To our knowledge, this is the
      first case of Netherton syndrome associated with idiopathic congenital
      hemihypertrophy to be reported.

PMID- 12220284
TI  - A rare association of epidermal nevus syndrome and ainhum-like digital
      constrictions.
AB  - Epidermal nevus syndrome is an unusual occurrence of epidermal nevi with central
      nervous system (CNS), eye, and skeletal developmental abnormalities. We report an
      as yet undocumented association of generalized epidermal nevus with striate
      keratoderma, ainhum-like digital constriction, and autoamputation of the right
      fifth toe in a 10-year-old girl. The excellent response to oral acitretin with
      softening of the constrictions is also highlighted.

PMID- 12220285
TI  - Rofecoxib-induced instant aquagenic wrinkling of the palms.
AB  - An 18-year-old woman presented with a 3-week complaint of exaggerated palmar
      wrinkling and swelling following brief exposure (1-2 minutes) of her hands to
      water. She had a history of mixed connective tissue disease and had been started
      on rofecoxib therapy 1 month prior to the onset of her skin symptoms.
      Discontinuation of rofecoxib was followed by resolution of symptoms within a
      period of 3 weeks. Similar palmar skin changes following water exposure have been
      reported to occur in cystic fibrosis and are thought to be due to increased salt
      content of the skin and secondary increased water-binding capacity. Rofecoxib is
      a selective COX-2 inhibitor that has been shown to increase sodium reabsorption
      in the kidney via effects on prostaglandin E2 and the renal vasculature. The COX
      2 protein is also expressed in keratinocytes and plays a role in keratinocyte
      differentiation. Prostaglandin E2 also plays a role in keratinocyte proliferation
      and differentiation. Thus rofecoxib may cause increased sodium reabsorption in
      the skin, as it does in the kidney. The rofecoxib-associated elevation in skin
      sodium may increase keratin water-binding capacity and cause exaggerated
      aquagenic wrinkling of the skin, as occurs in cystic fibrosis.

PMID- 12220286
TI  - Tinea capitis due to Trichophyton rubrum in a neonate.
AB  - Tinea capitis is a common infection of school-aged children, but there have been
      only a few reports of tinea capitis in newborns. Furthermore, Trichophyton rubrum
      as a causative organism of tinea capitis is documented very rarely. We report
      herein a neonate in whom T. rubrum was the causative agent. This boy was
      successfully treated with three pulses of oral itraconazole solution.

PMID- 12220287
TI  - D-penicillamine treatment for lipoid proteinosis.
AB  - Lipoid proteinosis, a rare disorder inherited in an autosomal recessive fashion,
      is characterized by the deposition of hyaline-like material in the skin, mucous
      membranes, and other tissues. Perturbation of collagen metabolism has been
      suggested to play an important role in the pathogenesis. No effective therapy is
      available for the disease. The chelating agent D-penicillamine has long been used
      to treat several diseases. In addition to its immunosuppressive and anti
      inflammatory effects, it also impairs fibroblast proliferation and inhibits the
      formation of the cross-links in collagen and elastin fibers. A 13-year-old girl
      was clinically and histologically diagnosed with lipoid proteinosis. We treated
      her with 600 mg/day of D-penicillamine for 2 years. The patient had improved
      clinically and histopathologically by the end of this treatment. We suggest D
      penicillamine as a promising agent, even in low doses, for the treatment of
      lipoid proteinosis.

PMID- 12220288
TI  - Congential lower lip pits.

PMID- 12220289
TI  - Localized lipodystrophy in a child.

PMID- 12220290
TI  - Dexpanthenol cream significantly improves mucocutaneous side effects associated
      with isotretinoin therapy.

PMID- 12220291
TI  - Granuloma annulare resolved with topical application of imiquimod.

PMID- 12220292
TI  - Epidermolysis bullosa acquisita in an 8-year-old girl.

PMID- 12220293
TI  - Verruca vulgaris surrounding a total graft following a burn in a child.

PMID- 12220294
TI  - Congenital infantile digital fibromatosis.

PMID- 12220296
TI  - The pathophysiological basis of acute-on-chronic liver failure.
AB  - The vast majority of patients that are referred to a specialist hepatological
      centre suffer from acute deterioration of their chronic liver disease. Yet, this
      entity of acute-on-chronic liver failure remains poorly defined. With the
      emergence of newer liver support strategies, it has become necessary to define
      this entity, its pathophysiology and the short and long-term prognosis. This
      review focuses upon how a precipitant such as an episode of gastrointestinal
      bleeding or sepsis may start a cascade of events that culminate in end-organ
      dysfunction and liver failure. We briefly review the pathophysiological basis of
      the therapeutic modalities that are available. Our current strategy for the
      management of liver failure involves supportive therapy for the end-organs with
      the hope that the liver function would recover if sufficient time for such a
      recovery is allowed. Because liver failure, whether of the acute or acute-on
      chronic variety, is potentially reversible, the stage is set for the application
      of newer liver support strategies to enhance the recovery process.

PMID- 12220297
TI  - Cholestatic liver disease: pathophysiology and therapeutic options.
AB  - Cholestasis results from defective canalicular secretion of bile or obstruction
      to bile flow distal to the canaliculus. In early primary biliary cirrhosis, bile
      secretion continues, because of the secretory pressure of bile or because some
      ductules are not obstructed. With complete cholestasis, a bile acid deficiency
      occurs in the small intestinal lumen leading to lipid maldigestion and fat
      soluble vitamin malabsorption. Bacterial proliferation, bacterial translocation
      to lymph nodes and endotoxemia may also occur leading to an acute phase reaction.
      Retention of bile acids in the hepatocyte leads to apoptosis. Accumulation of
      bile acids in the systemic circulation leads to pruritus, and may contribute to
      endothelial injury in the lungs and kidney. Early attempts to mimic hepatic
      excretory function by hemoperfusion over adsorbent columns were unsuccessful for
      a variety of reasons. Extracorporeal dialysis against albumin offers promise of a
      realistic albeit partial simulation of hepatic excretory function.

PMID- 12220298
TI  - Experiences with MARS liver support therapy in liver failure: analysis of 176
      patients of the International MARS Registry.
AB  - Extracorporeal liver support using the MARS recently has shown remarkable results
      in several trials. This study aims to extend the basis for analyses by making
      available the worldwide data with help of an international registry. One hundred
      and seventy six patients were analysed, main indications are acute-on-chronic
      liver failure (56%), acute liver failure (22%), primary graft dysfunction (15%),
      liver failure post liver surgery (4%) and miscellaneous (3%). The predicted
      survival within the first group based on a mean MELD score of 30.4 pts. and a
      mean Child score of 12.6 pts. was quite limited. The data suggest an improved
      survival accompanied by significant improvements of hepatic encephalopathy, mean
      arterial pressure, serum bilirubin level, creatinine, urea, albumin, INR, ammonia
      and MELD score. The results are confirming observations of other trials before
      which have shown MARS therapy to be an effective and safe extracorporeal liver
      support in liver failure.

PMID- 12220299
TI  - Economic evaluation of MARS--preliminary results on survival and quality of life.
AB  - OBJECTIVES: The short-term medical benefit of the liver dialysis system MARS in
      patients with severe acute liver disease has clearly been demonstrated. An
      economic analysis of MARS has not been presented previously. Objective of the
      study is to calculate the costs per life saved and life year gained and to
      measure health related quality of life in patients who survived acute liver
      failure. First results on survival and HRQL are presented here. STUDY DESIGN:
      Cost effectiveness and cost utility analysis of MARS are performed. All patients
      since 1993 with chronic liver failure (Bilirubin > 300 micro mol/l) of the
      university hospital Rostock are included in the original sample (n = 141).
      Survival data are calculated. Surviving patients were contacted personally, thus
      quality of life data (EQ 5D and SF12) determined. Patients were compared in case
      control study design. In a later stage inpatient hospital costs, direct and
      indirect outpatients costs are included in the analysis. PRELIMINARY RESULTS:
      MARS-Patients show a higher survival: Kaplan-Meier cumulative survival after 100
      days: 0.59 after MARS, 0.39 without (P <0.05). There was no significant
      difference in health related quality of life (SF12 and EQ-D). Calculations of
      quality adjusted life years (QALYs) result in 0.116 QALYs gained by treatment of
      one patient with MARS in one year. DISCUSSION: First preliminary results suggest
      that 1 year after therapy MARS seems to have a positive effect concerning
      survival rate, survival time and QALYs gained. Final results of cost
      effectiveness and cost-utility analysis will soon be presented.

PMID- 12220300
TI  - Extracorporeal liver support by recirculating albumin dialysis: analysing the
      effect of the first clinically used generation of the MARSystem.
AB  - Albumin dialysis with the MARSystem is used in many hospitals to support
      excretory hepatic function in acute or acute on chronic liver failure. Potential
      pathogenic albumin bound substances accumulated in excretory liver insufficiency
      can be removed from patients blood by dialysis against albumin solution. A
      specific membrane enables the selective transport of albumin bound metabolites to
      the albumin containing dialysate compartment, where the loaded transport albumin
      is cleared and regenerated at the same time by adsorption columns and a second
      dialyser. Between 1993 and 1995 different membranes, set-ups and components in
      albumin dialysis were tested and led finally to the recirculating MARSystem with
      a modified polysulphone based membrane (P3/5S Gambro, Hechingen) and two
      adsorption columns (N350 and BR 350, ASAHI Medical Ltd.), which showed the best
      performance at this time. This first generation of MARSystems was used clinically
      between 1995 and 1998 with only minor changes in 15 patients with acute (n = 1)
      or acute deterioration of chronic liver disease in our department until the
      improved next generation of MARSystems has been available (MARS set and monitor,
      Teraklin AG, Rostock, Germany). Changes in blood tests pre/post during 95 single
      MARS treatments and in clinical status over treatment period were evaluated
      retrospectively. RESULTS: A significant decrease of albumin bound substances
      (average reduction during single MARS treatments: bilirubin -18%, bile acids 
      43.7%) as well as of water soluble metabolites (creatinine -32%, urea -31%) was
      observed. During extracorporeal therapy also a significant drop in platelets (-
      15.4%) and a prolongation of activated prothrombin time (- 21%) was documented,
      whereas haemoglobin, WBC, electrolytes as well as transaminases and albumin were
      not affected significantly. CONCLUSION: Albumin dialysis with the first
      generation of MARS enables the removal of albumin bound and water soluble toxins.
      Unwanted side-effects and changes in laboratory tests are comparable to
      conventional haemodialysis (drop of platelets and prolongation of coagulation
      tests). The elimination of albumin bound and water soluble substances was
      accompanied by an improvement of clinical status.

PMID- 12220301
TI  - Amino acid dysbalance in liver failure is favourably influenced by recirculating
      albumin dialysis (MARS).
AB  - INTRODUCTION: Dysbalance between branched chain (BCAA) and aromatic amino acids
      (AAA), which can be quantified by a low Fischer's Index (SigmaBCAA/SigmaAAA), as
      well as elevated levels of free tryptophan in plasma are common in hepatic
      failure and may contribute to the development of hepatic encephalopathy. AIM: To
      evaluate the influence of a new extracorporeal detoxification system for liver
      failure (Molecular Adsorbents Recirculating System, MARS(R), i.e. dialysis
      against a recirculating albumin solution cleaned online by charcoal and an anion
      exchange resin) on plasma tryptophan and Fischer's Index. METHODS: Plasma samples
      were taken before, during and after MARS treatments (n = 11, mean blood flow 135
      ml/min, mean dialysate flow 120 ml/min, high flux polysulfone membrane).
      Simultaneous to blood sampling, aliquots of the albumin dialysate were taken
      between the elements of the dialysate circuit. RESULTS: Fischer's Index in
      systemic blood increased during MARS by 24% (from 1.44 to 1.79, P < 0.001; mean
      treatment duration, 5.5 h). Systemic tryptophan level was significantly reduced
      at the same time (-25%, n = 8). Amino acid removal rates from plasma during a
      single dialyser passage ranged from 10 to 53%. In particular, AAA were
      preferentially removed (42-44% throughout treatment), while BCAA removal was 28
      46% initially and later declined to 24-28%. A maximum concentration gradient
      between plasma and dialysate was maintained for the AAA throughout treatment
      through their apparently complete removal by the charcoal adsorber. Conversely,
      BCAA removal at both adsorbers was only minor. As a result, Fischer's Index
      showed a significant increase in the processed plasma, which became even more
      pronounced with increasing treatment duration. CONCLUSIONS: MARS enables an
      elevation of a pathologically decreased Fischer's Index as well as a reduction of
      systemic tryptophan levels in patients with liver failure. The effects of MARS on
      plasma amino acid dysbalance may contribute to an improvement of hepatic
      encephalopathy.

PMID- 12220302
TI  - Albumin dialysis: single pass vs. recirculation (MARS).
AB  - The single pass albumin dialysis (SPAD) was reported to be an alternative to the
      Molecular Adsorbent Recirculating System (MARS) for the effective removal of
      protein bound substances in liver failure. Three SPAD experiments using different
      albumin concentrations and dialysate flow rates were performed. In each
      experiment, 1000 ml human donor plasma, spiked with 250 mg unconjugated
      bilirubin, 200 mg sulfobromophthalein (BSP) and 115 mg glycocholic acid (N
      [3alpha,7alpha,12alpha-trihydroxy-24-oxycholan-24-yl]glycine) - a conjugated bile
      acid (BA), circulated in a closed loop with 150 ml/min and was dialysed against
      albumin solution. These substances are bound to the different binding sites of
      albumin and have different association constants. For the comparison, the
      standard MARS experiment was performed using the same plasma flow rate of 150
      ml/min. Moreover, the clearances of bilirubin for MARS and SPAD during clinical
      treatments were calculated using own data and those reported by Seige, Kreymann,
      Jeschke, et al. in Transplant Proc 1999; 31: 1371-5. The concentrations of
      bilirubin, BSP and BA were measured in plasma and dialysate and for these
      substances clearances (Cl) were calculated. It is known that the elimination rate
      of bilirubin is not very high during albumin dialysis in comparison to other
      substances, like bile acids, due to the high association constant. An increase of
      albumin concentration or the flow rate improved the efficacy but also raised the
      costs substantially. In this study, we have shown that MARS is the more effective
      kind of albumin dialysis for the important substances like bile acids. By SPAD an
      improvement of efficacy can be reached only by dramatic increase of the costs.
      Also, the earlier experiments showed that MARS is safer because of the removal of
      the stabilizers, which are normally included in the commercial albumin solutions.

PMID- 12220303
TI  - MARS (Molecular Adsorbent Recirculating System): experience in 34 cases of acute
      liver failure.
AB  - As reported in the literature, the mortality rates for patients with Acute
      Hepatic Failure (AHF) approaches 80% in cases in which liver transplantation is
      not possible. Post-transplant mortality mostly depends on the severity of the
      neurological condition at the time of the operation (20% in I-II degree coma
      patients and 44% in III degree coma patients). The primary indications for liver
      transplantation in AHF are Fulminant Hepatitis (FH)(93%), Subfulminant Hepatitis
      (5%) and other indications (2%). Other causes of AHF are Primary Non-Function
      (PNF) and Delayed Function (DF), which occur in 7-10%. Therefore it becomes
      necessary to monitor the patients with a Liver Support Device to be able to
      improve the clinical condition of the patients before liver transplantation (LT).
      In our experience we used the Molecular Adsorbent Recirculating System (MARS)
      (MARS Monitor; Teraklin AG, Rostock Germany), which enables the selective removal
      of albumin-bound substances accumulating in liver failure by the use of albumin
      enriched dialysate. The system is used as a bridging device to orthotopic liver
      transplantation (OLT) of patients with FHF. We studied 34 patients, including 16
      males and 18 females: 9 were affected by Primary-Non-Function (PNF), nine by
      Fulminant Hepatitis (FH), six by Delayed-Non-Function (DNF), and ten by Acute on
      Chronic Hepatic Failure (AOCHF). The average age of the patients was 41.8 years
      and the average number of applications was 6.4; the median length of application
      was about eight hours. The parameters that we monitored, before and after each
      treatment, were neurological status (EEG, cerebral CT, Glasgow Coma Score),
      haemodynamic parameters, acid base equilibrium, and blood gas analysis. We also
      monitored hepatic and renal function. In addition, the clinical conditions of the
      patients were monitored using kidney and liver ultrasound/ultrasonography (US).
      Inclusion criteria were bilirubin > 15 mg/dL, ammonia > 160 micro g/dL and a
      Glasgow Coma Score between 6 and 11. The reduction of bilirubin and ammonia were
      very significant (P < 0.01), whereas the changes of International Normalized
      Ratio (INR) were not significant. Also the modifications of albumin, total
      protein, sodium, potassium and calcium were not significant. In conclusion, four
      out of nine patients with PNF are alive without a second transplantation and were
      discharged after about 48 days; four out of nine underwent OLT, while one out of
      nine died; five out of six patients with DF are alive without a second
      transplantation, and they were discharged after an average time of 55.5 days, one
      out of six died; six out of nine patients with fulminant hepatitis underwent OLT
      and four of these are alive, while two died due to sepsis; three patients are
      alive without OLT. Four patients with AOCHF underwent OLT and are alive, three
      patients are alive and on a waiting list, two died while on a waiting list and
      one patient who experienced reactivation of HBV infection during chemotherapy for
      non-Hodgkin's lymphoma is alive. In spite of the limited number of cases of our
      study, we believe that MARS can be applied with high tolerance for a very long
      period of time. In addition, its repeatability allows it to be used in patients
      with DNF and FH as a bridge to transplant. In patients with DNF, it is used while
      waiting for complete recovery of the transplanted organ.

PMID- 12220304
TI  - Molecular Adsorbent Recirculating System: clinical experience in patients with
      liver failure based on hepatitis B in China.
AB  - The aim of this study is to evaluate the effect of treatment with the Molecular
      Adsorbent Recirculating System (MARS) on liver failure based on HBV. In 25
      patients (median age, 36.3 years, range, 22-67 years, bilirubin level > 255 micro
      mol/l) admitted with liver failure based on HBV, the 6-8h MARS intermittent
      treatments were performed without any adverse events, A significant decrease in
      bilirubin, ammonia and urea levels were observed (P < 0.05). All patients
      achieved a remarkable neurologic recovery, particularly 2 HE-III and 3 HE-IV
      patients regained normal consciousness, respectively. The survival rate for the
      patients whose treatments kept to the MARS art strategy was 76.9% (10/13), while
      the others only had the survival rate of 16.7% (2/12) due to their giving up
      sequential MARS treatments after the first time. The rebounding rate of the
      bilirubin level in the patients after a single MARS treatment was significantly
      lower than that of patients, who underwent a single plasma-exchange treatment (P
      < 0.01). It is concluded that MARS method can contribute to the optimistic
      treatment of liver failure patients based on HBV which being the major epidemic
      liver disease in China.

PMID- 12220305
TI  - The Molecular Adsorbent Recirculating System in patients with severe liver
      failure: clinical results at the K.U. Leuven.
AB  - BACKGROUND: The Molecular Adsorbent Recirculating System (MARS) is a novel
      extracorporeal technique for liver support. We report the clinical results in the
      first 13 patients with severe liver failure treated at our institution. METHODS:
      Patients with acute or acute on chronic liver failure of various aetiologies were
      treated with varying numbers of MARS sessions of six hours duration. RESULTS:
      Mean APACHE II score was 18. In general, patients with multiple organ failure
      faired poorly even with MARS treatment. Five patients (38%) survived the
      hospitalisation. Eight patients (62%) fulfilled criteria for UNOS type I or 2 A
      status. Two of these patients survived. Five patients had a UNOS 2B status and
      three survived. In proportion, patients with severe itch, patients with primary
      non-function and those where MARS was used as a bridge to transplantation seemed
      to profit most from the treatment. The median reduction in bilirubin
      concentrations after the treatment period was -28.2%. In survivors, the median
      reduction was -37.7% and in patients who died was -15.9%. The median
      encephalopathy score improved from 1.7 to 0.5. CONCLUSION: The molecular
      adsorbent recycling system (MARS) might be lifesaving in patients with severe
      liver failure of different aetiologies.

PMID- 12220306
TI  - Application of Molecular Adsorbent Recirculating System in patients with severe
      liver failure after hepatic resection or transplantation: initial single-centre
      experiences.
AB  - Acute liver failure after hepatic surgery is still plaqued with high mortality
      rate. Recently, a liver dialysis system (MARS) that allows detoxification of
      albumin-bound substances and may hereby support liver regeneration and patient's
      recovery has been developed. In the present study, we report our experiences with
      MARS dialysis in patients with liver failure after hepatic resection or
      transplantation. Between September 1999 and January 2001, five patients were
      treated with MARS (2-5 courses). Though beneficial effects such as improvement of
      encephalopathy and renal function as well as reduced bilirubin levels were
      recorded during MARS therapy, only one patient survived. Neither significant
      technical problems nor adverse effects occurred by using MARS dialysis. We
      conclude that in surgical patients, acute liver failure is usually part of a
      complicated clinical course affecting multipleorgan systems. Thus, it is
      difficult to determine the specific influence of MARS on patient's outcome.
      However, beneficial effects observed in our patients justify its continuous use
      and may stimulate further evaluation in controlled studies with surgical
      patients.

PMID- 12220307
TI  - First clinical experience with Molecular Adsorbent Recirculating System (MARS) in
      six patients with severe acute on chronic liver failure.
AB  - Despite recent advances in general supportive care, the mortality rate of
      patients with severe liver insufficiency remains high. Recently a new artificial
      liver support system MARS has been used for selective removal of albumin-bound
      toxins. AIM: To assess the safety and efficacy of MARS treatment in patients with
      acute on chronic liver disease (n = 5) or liver failure after extended hepatic
      resection (n = 1). DESIGN/PATIENTS: Six patients, aged 34-58 years, with severe
      liver insufficiency (mean MELD-score 31 (range 24-35)) were treated one to 16
      times with the MARS system. At baseline three patients were intubated, three were
      encephalopathic (HE) and three had multifactorial kidney failure requiring kidney
      replacement therapy. RESULTS AND CONCLUSION: In all the patients MARS treatment
      significantly reduced the serum bilirubin levels. In three patients
      encephalopathy improved. In two patients the extracorporeal treatment
      precipitated a disseminated intravascular coagulation with clinically significant
      bleeding. Bridging to liver transplantation was possible in one patient, the
      other five patients died 30 days (2-74 days) after starting MARS therapy. Our
      case series shows that MARS treatment in general can be safely performed in
      patients with severe liver disease. However, in patients with an activated
      clotting system severe bleeding complication can be triggered and MARS treatment
      should be used very cautiously in these situations. MARS seems to be a promising
      new treatment option for patients with acute on chronic liver failure. However,
      carefully conducted randomized controlled trials are necessary to define its
      potential place in the treatment of patients with severe liver disease.

PMID- 12220308
TI  - Emerging indications for MARS dialysis.
AB  - MARS stands for Molecular Adsorbent Recirculating System and represents an
      interesting option in treating patients with liver disease. There is still little
      known about the best time point of initiating this treatment and the exact
      selection criteria for patients who may benefit from this therapy. The list of
      potential applications using this procedure is expanding. We report on the
      experience in seven patients being treated with MARS dialysis for chronic
      cholestatic liver disease and acute on chronic liver failure. From August 2000 to
      October 2001 seven patients received 27 MARS treatments in our clinic, ranging
      from 2 to 12 treatments per subject. Presented cases were diagnosed as
      steatohepatitis because of alcoholism (n = 3), vanishing bile duct disease (n =
      1), metabolic liver disease (n = 1), primary biliary cirrhosis (n = 1) and drug
      induced hepatitis (n = 1). Based on this experience, we discuss the ongoing
      questions of various indications and the decision to initiate MARS dialysis.

PMID- 12220309
TI  - Modular extracorporeal life support for multiorgan failure patients.
AB  - Adults receiving respiratory Extracorporeal Membrane Oxygenation (ECMO) have 66%
      survival. Nonsurvivors develop multisystem organ failure (MSOF). Once hepatic
      failure develops, death usually follows shortly. Serum bilirubin > 300 micromol/l
      predicted death with 87.8% sensitivity and 90.3% specificity in 41 adults who
      received ECMO in our institution during 1998 and 1999. No patients survive with a
      peak bilirubin > 400 micromol/l. The Molecular Adsorbent Recirculating System
      (MARS) is a cell-free extracorporeal liver support device; we hypothesized that
      using MARS in adult respiratory ECMO patients with a bilirubin >300 micromol/l
      could improve survival in MSOF. The MARS was used in five such patients aged 19
      56 who developed liver failure secondary to a respiratory illness. Mean peak
      bilirubin was 529 micromol/l and the lowest peak bilirubin was 436 micromol/l.
      Patients received between 1 and 8 MARS treatments, mean reduction in serum
      bilirubin for each patient ranging between 30 and 162 micromol/l. Two of five
      patients survived (40%), survivors showing the greatest reduction in serum
      bilirubin in response to MARS. All patients would have been expected to die
      according to our previous experience. We believe that MARS may prove a useful
      therapy for patients with MSOF.

PMID- 12220310
TI  - Extracorporal albumin dialysis (MARS) improves cholestasis and normalizes low apo
      A-I levels in a patient with benign recurrent intrahepatic cholestasis (BRIC).
AB  - The familial cholestatic diseases Benign Recurrent Intrahepatic Cholestasis
      (BRIC) and Progessive Familial Intrahepatic Cholestasis type 1 (PFIC1) are
      characterized by intermittent or permanently elevated plasma bile salt levels,
      therapy-resistant extreme pruritus and peculiar biochemical abnormalities
      including low apolipoprotein apo A-I. Previously, symptomatic improvement has
      been demonstrated in BRIC patients after extracorporal albumin dialysis (MARS).
      We hypothesized that MARS improves cholestasis, induces changes in the bile salt
      profile and normalizes apo A-I serum levels in BRIC. A 17-year-old-female patient
      with BRIC experienced an episode of cholestasis lasting for more than 6 months
      with extreme pruritus and diarrhoea not responding to standard therapy. During a
      period of five days the patient was treated 3 x 8 h with MARS. The procedures
      were well tolerated and resulted in reduction of plasma bile salts by 58%. The
      plasma bile salt profile changed into a more hydrophilic composition after MARS.
      Diarrhoea discontinued and the pruritus improved significantly from 9 to 4 on a
      subjective scale. These effects lasted 4 months until a relapse occurred. Low
      plasma apo A-I levels (0.52 g/l) normalized after MARS (0.98 g/l). The procedures
      were well tolerated. Fatigue was noted as the only transient side-effect. In
      conclusion, MARS may induce a long-term symptomatic improvement and decrease of
      cholestatic markers in BRIC. Further studies evaluating efficacy and mechanism of
      MARS in patients with BRIC are needed.

PMID- 12220311
TI  - MARS procedure as a bridge to combined liver-kidney transplantation in severe
      chromium-copper acute intoxication: a paediatric case report.
AB  - We describe a case of multi-organ failure (liver-kidney insufficiency and brain
      oedema) caused by accidental, acute intoxication with a chromium and copper
      containing substance, as an example of the introduction of the new extracorporeal
      procedure MARS (molecular adsorbents recirculating system) in a girl 3.5 years
      old.

PMID- 12220312
TI  - MARS: optimistic therapy method in fulminant hepatic failure secondary to
      cytotoxic mushroom poisoning--a case report.
AB  - BACKGROUND: Poisoning by cytotoxic mushrooms (Amanita phalloides and related
      species) is associated with severe morbidity and a high mortality rate (lethality
      > 20% in adults and > 50% in children). The main causes of this intoxication are
      the amatoxines, which inhibit DNA-dependent RNA Polymerase II or B. This
      interaction leads to a tight complex, and the inhibition is of a non-competitive
      type (1); in addition to those tight binding inhibitors of adenosine kinase,
      papain, cathepsin L, cathepsin B, cysteine proteinase and bromelain (2), inhibit
      the synthesis of messenger RNA in the hepatocytes, decrease the formation of
      coagulation factors and of immunoglobulins and effect a vasoconstriction. They
      also have an influence on the transcription and lesions that are seen in cells
      with rapid protein synthesis, particularly in liver and renal cells, with the
      cellular changes causing the fragmentation and segregation of all nuclear
      components, even at low toxin concentrations (3). Phallotoxin, which is the other
      toxin isolated from death cap, binds with a high affinity to microfilamentous
      structures - in particular, to F-actin, which stimulates the polymerization of G
      actin, stabilizes the F-actin filaments, irreversibly polymerizes actin filaments
      and causes cholestasis (4). Liver is recognized as the target organ for Amanita
      phalloides toxins; it is presented by fatty degeneration, acute toxic dystrophy
      and centrilobular necroses (5). Therapeutic options employed to treat mushroom
      intoxication, such as hemodiaperfusion on activated charcoal, high dosages of
      penicillin G, oral charcoal, etc., very often failed to act properly and liver
      transplantation (when a graft is available) appeared to be the only solution. The
      most polarized debate concerns the value of extracorporeal elimination.
      Plasmapheresis and peritoneal dialysis proved much less useful for this purpose;
      neither haemodialysis (HD) nor haemoperfusion (HP) contributed to the clearance
      of amatoxin (6, 7). Recently, Stange et al. (8). introduced a new detoxication
      method (referred to as MARS) for protein-bound substances in patients with liver
      failure and grade III and IV hepatic encephalopathy. MARS was performed with an
      albumin-containing dialysate, which is recycled in a closed loop that contains a
      charcoal cartridge, an anion exchanger resin adsorber and a conventional
      haemodialyser. With dialysis using an albumin-containing dialysate, protein-bound
      substances, which are usually not sufficiently dialysable, can be eliminated. The
      treatments increase the rate of toxin elimination to the extent that the toxic
      exposure of highly susceptible cells, such as hepatocytes, is minimized. This
      leads to the surprise recovery of the poisoning patient, despite her severe
      condition, even as late as up to a week after mushroom ingestion.

PMID- 12220313
TI  - A simple way to measure daily lifestyle regularity.
AB  - A brief diary instrument to quantify daily lifestyle regularity (SRM-5) is
      developed and compared with a much longer version of the instrument (SRM-17)
      described and used previously. Three studies are described. In Study 1, SRM-17
      scores (2 weeks) were collected from a total of 293 healthy control subjects
      (both genders) aged between 19 and 92 years. Five items (1) Get out of bed, (2)
      First contact with another person, (3) Start work, housework or volunteer
      activities, (4) Have dinner, and (5) Go to bed were then selected from the 17
      items and SRM-5 scores calculated as if these five items were the only ones
      collected. Comparisons were made with SRM-17 scores from the same subject-weeks,
      looking at correlations between the two SRM measures, and the effects of age and
      gender on lifestyle regularity as measured by the two instruments. In Study 2
      this process was repeated in a group of 27 subjects who were in remission from
      unipolar depression after treatment with psychotherapy and who completed SRM-17
      for at least 20 successive weeks. SRM-5 and SRM-17 scores were then correlated
      within an individual using time as the random variable, allowing an indication of
      how successful SRM-5 was in tracking changes in lifestyle regularity (within an
      individual) over time. In Study 3 an SRM-5 diary instrument was administered to
      101 healthy control subjects (both genders, aged 20-59 years) for two successive
      weeks to obtain normative measures and to test for correlations with age and
      morningness. Measures of lifestyle regularity from SRM-5 correlated quite well
      (about 0.8) with those from SRM-17 both between subjects, and within-subjects
      over time. As a detector of irregularity as defined by SRM-17, the SRM-5
      instrument showed acceptable values of kappa (0.69), sensitivity (74%) and
      specificity (95%). There were, however, differences in mean level, with SRM-5
      scores being about 0.9 units [about one standard deviation (SD)] above SRM-17
      scores from the same subject-weeks. SRM-5 scores also deviated more from a
      Gaussian distribution than did SRM-17 ones. In a study with a sample size of 101,
      the new SRM-5 instrument yielded scores with a mean of 4.11 and an SD of 1.13.
      Correlations between lifestyle regularity and age, and between lifestyle
      regularity and morningness appeared similar whether 5-item or 17-item SRM
      measures were used. When a gender difference in lifestyle regularity appeared, it
      was detected by both SRM-5 and SRM-17 measures.

PMID- 12220314
TI  - Circadian preference, sleep and daytime behaviour in adolescence.
AB  - The aim of this study was to determine the relationship between circadian
      preferences, regularity of sleep patterns, sleep problems, daytime sleepiness and
      daytime behaviour. As a part of an epidemiological survey on sleep in a
      representative sample of Italian high-school students, a total of 6631
      adolescents, aged 14.1-18.6 years, completed the School Sleep Habits Survey, a
      comprehensive questionnaire including items regarding sleep, sleepiness,
      substance use, anxiety and depressed mood, use of sleeping pills, school
      attendance and a morningness/eveningness scale. The sample consisted of 742
      evening-types (315 males and 427 females; mean age 17.1 years) and 1005 morning
      types (451 males and 554 females; mean age 16.8 years). No significant sex
      differences were found for morningness/eveningness score. Eveningness was
      associated with later bedtime and wake-up time, especially on weekends, shorter
      time in bed during the week, longer weekend time in bed, irregular sleep-wake
      schedule, subjective poor sleep. Moreover, evening types used to nap more
      frequently during school days, complained of daytime sleepiness, referred more
      attention problems, poor school achievement, more injuries and were more
      emotionally upset than the other chronotype. They referred also greater caffeine
      containing beverages and substances to promote sleep consumption. Our results
      suggest that circadian preference might be related not only to sleep pattern, but
      also to other adolescent behaviours.

PMID- 12220315
TI  - Regional cerebral blood flow during light sleep--a H(2)(15)O-PET study.
AB  - This is the first report on the distribution of regional cerebral blood flow
      (rCBF) changes during stage-1 sleep or somnolence. Two hypotheses were tested:
      (A) that rCBF differed between the awake relaxed state and stage-1 sleep, (B)
      that hypnagogic hallucinations frequently experienced at sleep onset would be
      accompanied by measurable changes in rCBF using positron emission tomography
      (PET). Eight subjects were PET-scanned with (15)O-labeled water injection in
      three conditions: awake, stage-1 sleep with reportable experiences and stage-1
      sleep without reportable experiences. Electroencephalography (EEG) was performed
      continuously during the experiment. Sleep interviews were performed after each
      scan. The EEG was scored blindly to determine sleep stage. The sleep interviews
      revealed a substantial increase in how unrealistic and how leaping the thoughts
      were during stage-1 sleep. During sleep there was a relative flow increase in the
      occipital lobes and a relative flow decrease in the bilateral cerebellum, the
      bilateral posterior parietal cortex, the right premotor cortex and the left
      thalamus. Hypnagogic experiences seemed not to be associated with any relative
      flow changes. The topography of the occipital activation during stage-1 sleep
      supports a hypothesis of this state being a state of imagery. The rCBF decreases
      in premotor cortex, thalamus and cerebellum could be indicative of a general
      decline in preparedness for goal directed action during stage-1 sleep. Stage-1
      sleep seems more similar to other forms of altered awareness, for example,
      relaxation meditation than to deeper sleep stages. We are of the opinion that
      stage-1 sleep represents the dreaming state of wakefulness, while rapid eye
      movement (REM) sleep reflects the dreaming state of the unaware, sleeping brain.

PMID- 12220316
TI  - Correlates of nap taking in mothers of young infants.
AB  - Many researchers and clinicians have promoted nap taking to combat the
      deleterious effects of disrupted sleep. Unfortunately, only a small portion of
      sleep-deprived individuals take naps. The goal of the present study was to
      identify cognitive and opportunity factors related to nap taking of mothers of
      young infants. Fifty-one mothers of young infants completed measures that
      recorded various characteristics of their nighttime sleep patterns, their
      perceptions of their sleep, and factors influencing their opportunities to take
      naps. Results revealed that mothers' perceptions of sleep disturbance and
      opportunity factors were more predictive of napping than total nighttime sleep or
      actual time spent caring for the infant during the night.

PMID- 12220317
TI  - The recuperative value of brief and ultra-brief naps on alertness and cognitive
      performance.
AB  - The aim of the study was to investigate the recuperative value of brief and ultra
      brief naps following nocturnal sleep restriction. Sixteen young adult healthy
      sleepers participated in a repeated measures design comprising four experimental
      conditions: no nap, 30-s nap, 90-s nap and 10-min nap. On the evening preceding
      each laboratory session, participants limited their nocturnal sleep to between
      24:00 and 05:00 h. Measures of subjective alertness, objective alertness,
      fatigue, vigour and cognitive performance were taken before the nap and at
      several intervals postnap. Consistent with our previous study (Tietzel and Lack
      2001), the 10-min nap resulted in significantly improved alertness and cognitive
      performance relative to a no-nap control. There were no measurable improvements
      for the 30- and 90-s nap conditions relative to no nap, which suggests that the
      mechanism underlying the benefits of brief naps does not appear to be the onset
      of stage 1 sleep. Further research is required to investigate whether the
      benefits of brief naps are because of the onset of stage 2 or delta wave sleep,
      or a specific duration of sleep between 90 s and 10 min.

PMID- 12220318
TI  - The impact of a nap opportunity during the night shift on the performance and
      alertness of 12-h shift workers.
AB  - The purpose of this workplace evaluation was to assess the effects on
      performance, alertness and subsequent sleep of strategic napping on 12-h
      overnight shifts. In a counterbalanced crossover design, 24 male aircraft
      maintenance engineers working in a forward rotating 12-h shift pattern
      volunteered to take part in the study for two work weeks. During the experimental
      week, each subject was given the opportunity to take a 20-min nap at work between
      01:00 and 03:00 h on each of their two overnight shifts. On the control week no
      naps were taken on the night shifts. A computerized neurobehavioural test battery
      was employed to assess performance and subjective levels of fatigue at the
      beginning and end of each night shift, and pre- and postnap. Subjects were also
      asked to rate how near they had come to falling asleep while driving to and from
      work. The results revealed that taking a single 20-min nap during the first night
      shift significantly improved speed of response on a vigilance task measured at
      the end of the shift compared with the control condition. On the second night
      shift there was no effect of the nap on performance. Taking a short nap during
      either night shift had no significant effect on subjective ratings of fatigue,
      the level of sleepiness reported while driving to and from work, or subsequent
      sleep duration and sleep quality. Overall the results suggest some promise for a
      short duration nap taken in the workplace to counteract performance deficits
      associated with the first night shift.

PMID- 12220319
TI  - Towards an understanding of self-reports of sleep.
AB  - Sleep research has made extensive use of self-report measures relying on a
      response format that requires respondents to provide single, specific numerical
      estimates. The cognitive processes involved in storing and retrieving sleep
      related information allow only approximate numeric estimates of sleep behavior.
      Based on a fuzzy set model of survey responses, a response format is proposed to
      better capture the inherent vagueness of quantitative estimates of sleep
      behavior. Ninety-three adults (mean age 29.3 years) participated in two
      interviews, 1 month apart, consisting of questions about health-related
      behaviors. Questions were asked in both traditional point estimate and fuzzy
      response formats. A subset of questions was repeated at the end of each interview
      to examine test-retest reliability. Subjects filled out daily diaries each
      morning during the month between interviews. Quantitative estimates of usual
      sleep behavior were found to be highly reliable. Point estimates differed
      significantly from fuzzy boundary estimates. Differences between lower and upper
      boundary estimates indicated substantial ranges in estimates of usual sleep:
      total sleep time (6-8.2 h), sleep latency (26-44 min), bed time (11:25 PM-12:56
      AM) and waking time (7:24-8:39 AM). Mean diary-recorded bed and waking times fell
      between the lower and upper boundary estimates in more than 53% of cases, and
      between the lower and upper extreme estimates in more than 92% of cases. Fuzzy
      response formats provide an opportunity to report more completely what can be
      recalled about sleep behavior. They also provide a useful framework for better
      understand the meaning of traditional point estimate formats.

PMID- 12220320
TI  - Copulatory activity increases slow-wave sleep in the male rat.
AB  - It is believed that sexual activity increases the need to sleep in many species.
      However, the relationship between copulatory activity and sleep has been poorly
      studied. Several studies have observed variations in the sleep of female rats and
      women as a function of their reproductive state. These effects have been
      correlated with the effects of female steroid hormones, but not with sexual
      activity. The aim of the present study was to evaluate the sleep-wake pattern of
      male rats immediately after different conditions of copulatory activity. Sexually
      experienced male rats were chronically implanted with a standard set of
      electrodes for sleep recording. After a control sleep recording of 8 h, the males
      were randomly assigned to one of the following experimental conditions: 30 min in
      the presence of an ovariectomized (OVX) rat; 30 min in the presence of an intact
      non-receptive female (NRF); with a receptive female until reaching one
      ejaculation (1E); and with a receptive female until reaching three ejaculations
      (3E). In addition, after 10 days, males were randomly exposed to one of the
      following copulatory conditions during 4 h: to remain in the presence of an OVX
      rat; to remain in the presence of an NRF female, and with receptive females until
      reaching sexual satiety (SS). Male sexual behavior was assessed just after the
      onset of the dark period, and sleep recordings were obtained during 8 h
      immediately after experimental testing. Both the three ejaculations group (3E) in
      the first experiment and the sexual satiety group (SS) in the second experiment
      showed enhanced percentages of time spent in slow wave sleep (SWS) II and a
      shorter latency to the first SWS II episode than in the control group or under
      basal conditions. In addition, neither the presence of a non-receptive female or
      an OVX female, nor sexual behavior until reaching one ejaculation induced any
      effect on the sleep stages. These findings suggest that the increase in SWS II
      induced by both 3E and SS may be governed by some specific mechanism that is
      essentially independent of physical exercise or stress. Copulatory activity might
      be the source of neurohormonal processes that induce sleep and may involve the
      participation of gamma-aminobutyric acid, serotonin or other endogenous
      regulators of sleep and wakefulness. Nevertheless, the precise mechanism by which
      the sexual behavior increases SWS is still to be determined.

PMID- 12220321
TI  - The effects of alcoholism on auditory evoked potentials during sleep.
AB  - Normal aging is associated with a reduction in the probability that an auditory
      stimulus will evoke a K-complex during sleep. Additional concomitants of aging
      are a reduction in the amplitude of the K-complex-related N550, an augmentation
      of the P2 component and the appearance of a long-lasting positivity (LLP) in the
      auditory evoked potential. Normal aging is also associated with a dramatic
      reduction in slow wave sleep (SWS) and a reduction in the volume of cortical gray
      matter, particularly in the frontal and prefrontal regions of the brain. As in
      aging, alcoholism is associated with reductions in both cortical gray matter and
      SWS. It can, therefore, be hypothesized that alcoholics would show similar evoked
      potential changes to those seen in aging. To test this hypothesis, we studied
      seven middle-aged abstinent long-term alcoholics and eight age-matched normal
      controls. Each subject spent one night in the laboratory. Electroencephalogram
      (EEG) was recorded from six midline scalp sites and auditory stimuli were
      presented during stage 2 non-rapid eye movement sleep. N550 amplitude in the K
      complex average was lower in the alcoholics as compared with controls as was the
      likelihood of K-complex production. No differences were noted in either amplitude
      or latency of the P2 or N350 components, and both groups displayed a prominent
      LLP potential. The pattern of reduced K-complex production and N550 amplitude in
      alcoholics as compared with age-matched controls is consistent with an
      hypothesized association between atrophy of the frontal lobes and reductions in
      SWS and K-complexes. The finding also suggests that the evoked K-complex may be a
      relatively simple measure of the effect of alcoholism on EEG during sleep.

PMID- 12220322
TI  - The effects of levetiracetam on objective and subjective sleep parameters in
      healthy volunteers and patients with partial epilepsy.
AB  - Levetiracetam is a novel antiepileptic drug which has recently been released as
      an adjunctive treatment for partial epilepsy. In the two studies reported here we
      examined the objective and subjective effects of levetiracetam on sleep in 12
      healthy volunteers and 17 patients [16 who could be evaluated for
      electroencephalogram (EEG) recordings] with a history of partial epilepsy on
      stable carbamazepine monotherapy. The studies were of a similar double-blind
      crossover placebo-controlled design with subjects' sleep being recorded in their
      own homes. The results from the two studies showed considerable similarities. In
      both, levetiracetam produced an increase in the time spent in stage 2 sleep,
      which in the patient study was accompanied by a decrease in the time spent in
      stage 4 sleep and in the volunteer study an increase in rapid eye movement (REM)
      latency. The subjective changes included reports that sleep was of a better
      quality with fewer awakenings and patients also reported that their sleep was
      more restful. Volunteers and patients did, however, feel less alert on waking in
      the morning. Therefore, both groups reported a decrease in awakenings after
      levetiracetam despite the finding from the EEG of no change in the actual number
      of awakenings. It may be concluded from both studies that levetiracetam does
      affect some indicators of subjective sleep perception, but does not influence
      objective sleep measures of sleep continuity. The results from the patient study
      during placebo add-on treatment also showed that patients on carbamazepine had a
      marked increase in SWS, an increase in stage 2 sleep and an increase in REM
      latency compared with healthy volunteers. Interestingly, levetiracetam also
      reduced bilateral epileptiform EEG activity, particularly in patients with more
      discharges.

PMID- 12220323
TI  - Measures of cognitive function in persons with varying degrees of sleep
      disordered breathing: the Sleep Heart Health Study.
AB  - Epidemiologic literature suggests that persons with clinically diagnosed sleep
      apnoea frequently have impaired cognitive function, but whether milder degrees of
      sleep-disordered breathing (SDB) are associated with cognitive dysfunction in the
      general population is largely unknown. Approximately 1700 subjects free of
      clinically diagnosed SDB underwent at-home polysomnography (PSG) as part of the
      Sleep Heart Health Study (SHHS) and completed three cognitive function tests
      within 1-2 years of their PSG: the Delayed Word Recall Test (DWR), the WAIS-R
      Digit Symbol Subtest (DSS), and the Word Fluency test (WF). A respiratory
      disturbance index (RDI) was calculated as the number of apnoeas and hypopnoeas
      per hour of sleep. After adjustment for age, education, occupation, field centre,
      diabetes, hypertension, body-mass index, use of CNS medications, and alcohol
      drinking status, there was no consistent association between the RDI and any of
      the three cognitive function measures. There was no evidence of a dose-response
      relation between the RDI and cognitive function scores and the adjusted mean
      scores by quartiles of RDI never differed from one another by more than 5% for
      any of the tests. In this sample of free-living individuals with mostly mild to
      moderate levels of SDB, the degree of SDB appeared to be unrelated to three
      measures of cognitive performance.

PMID- 12220324
TI  - Undetectable CSF level of orexin A (hypocretin-1) in a HLA-DR2 negative patient
      with narcolepsy-cataplexy.

PMID- 12220325
TI  - Hepatic mitochondrial dysfunction in senescence-accelerated mice: correction by
      long-term, orally administered physiological levels of melatonin.
AB  - Mitochondrial oxidative damage from free radicals may be a factor underlying
      aging. We investigated whether long-term administration of physiological levels
      of melatonin, a direct free radical scavenger and indirect antioxidant,
      influences mitochondrial respiratory activity in liver of senescence-accelerated
      mice (SAM). Liver was obtained in the middle of dark period of the daily
      light:dark cycle from SAMP8, a strain of mice prone to accelerated senescence,
      and from SAMR1, a senescence-resistant strain, at 6 and 12 months of age.
      Respiratory control index (RCI), adenosine-5-diphosphate (ADP)/O ratio, State 3
      respiration and dinitophenol (DNP)-dependent uncoupled respiration exhibited
      significant age-associated decreases in SAMP8. SAMP8 also showed significant age
      associated reductions in respiratory chain complex I and IV activities. No age
      related effects were found in these parameters in SAMR1. Daily oral melatonin
      administration (2 microg/mL of drinking fluid) beginning at 7 months of age
      significantly increased RCI, State 3 respiration, DNP-dependent uncoupled
      respiration, and complex I and IV activities in both mouse strains when they were
      12 months old. These results reveal age-related reductions in mitochondrial
      function in SAM mice which are modified by melatonin; the most likely explanation
      for the corrective actions of melatonin relate to its antioxidative actions in
      mitochondria and other portions of the cell. The implication of the findings is
      that melatonin may be beneficial during aging as it reduces the deteriorative
      oxidative changes in mitochondria and other portions of the cell associated with
      advanced age.

PMID- 12220326
TI  - Altered glial fibrillary acidic protein content and its degradation in the
      hippocampus, cortex and cerebellum of rats exposed to constant light: reversal by
      melatonin.
AB  - Reactive astrocytosis is a well-known phenomenon that occurs rapidly after
      physical or metabolic injury to the brain. One of the important events during
      astrocyte differentiation is the increased expression of glial fibrillary acidic
      protein (GFAP), a member of the family of intermediate filament structural
      proteins. Free radicals are neurotoxic and free radical scavengers have been
      shown to protect the brain against neurotoxic damage. In the present study, we
      examined the effect of melatonin on astrocytic reactivity by determining the
      expression of the glial marker, GFAP, in different brain regions. Rats were
      exposed to constant light to reduce endogenous melatonin production; half of the
      animals were injected with melatonin during the exposure to constant light for 7
      days. Western blots showed increases in total and degraded GFAP content in the
      brain of rats exposed to constant light. Melatonin administration caused a
      reduction of degraded GFAP content. In addition, melatonin significantly reduced
      neural tissue lipid peroxidation while constant light significantly enhanced the
      breakdown of lipids in the brain. Brain glutathione levels decreased
      significantly as a result of constant light exposure; this reduction was reversed
      by melatonin administration. These results suggest that melatonin potentially
      protects both neurons and glial cells from free radicals; melatonin's protective
      actions are probably related to the antioxidant properties of the indole.

PMID- 12220327
TI  - Variations of mt1 melatonin receptor density in the rat uterus during
      decidualization, the estrous cycle and in response to exogenous steroid
      treatment.
AB  - The expression of mt1 receptor protein in the rat uterus was investigated using
      an anti-mt1 polyclonal antibody against the rat mt1 receptor. A melatonin
      receptor protein of 37 kDa was detectable by Western blotting in the rat uterine
      membrane preparations. Autoradiography with the melatonin ligand, 2
      [125I]iodomelatonin, was used to localize melatonin receptors in the uterus of
      the estrous rats and to study the changes of melatonin receptors in pregnancy.
      Melatonin receptors were found to be localized in the estrous rat uterine
      antimesometrial stroma. As decidualization of the uterine stroma progressed
      during pregnancy, the melatonin binding sites were progressively reduced and
      became confined to the antimesometrial non-decidualized outer stroma. 2
      [125I]Iodomelatonin binding sites were not seen in the mesometrial stromal cells
      during pregnancy. The role of ovarian hormones in the regulation of uterine
      melatonin receptors was examined by studying the binding at various phases of the
      estrous cycle, after ovariectomy with and without follow-on treatment of
      estradiol (E2), progesterone (P4) or both. 2-[125I]Iodomelatonin binding in the
      rat uterus fluctuated during the estrous cycle, being lowest during metestrus.
      Ovariectomy caused an almost 70% reduction of 2-[125I]iodomelatonin binding
      compared with the control. Injections of ovariectomized (OVX) rats with E2 or P4
      alone or in combination for 11 days induced a partial restoration of 2
      [125I]iodomelatonin binding in the OVX rats. The results show that mt1 melatonin
      receptors in the rat antimesometrial stroma are regulated by ovarian hormones.

PMID- 12220328
TI  - Melatonin suppresses NO-induced apoptosis via induction of Bcl-2 expression in
      PGT-beta immortalized pineal cells.
AB  - In the present study, we investigated whether melatonin would prevent nitric
      oxide (NO)-induced apoptotic death of PGT-beta immortalized pineal cells. To
      examine the protective effect of melatonin, cytotoxicity assay, DNA fragmentation
      analysis, caspase-3 activity assay, and Western blotting for caspase-3 and
      poly(ADP-ribose) polymerase (PARP) were performed. Treatment of cells with S
      nitroso-N-acetylpenicillamine (SNAP), an NO donor, was shown to induce apoptotic
      cell death in a dose-dependent manner, and pretreatment with melatonin (0.1 mm)
      attenuated the occurrence of NO-induced apoptotic cell death. DNA fragmentation
      in response to NO was also arrested by melatonin. Caspase-3 activity induced by
      NO was decreased with melatonin treatment. Furthermore, the active fragments of
      caspase-3 and PARP were almost completely absent following exposure to melatonin.
      To elucidate the protective mechanisms of action of melatonin, Western blot
      analyses for Bcl-2 expression and cytochrome c release were carried out.
      Pretreatment with melatonin (0.1 mm) induced the expression of Bcl-2 and
      suppressed the release of cytochrome c into the cytosol, thereby arresting NO
      induced apoptotic cell death. These results suggest that the antiapoptotic effect
      of melatonin is associated with induction of Bcl-2 expression in PGT-beta cells,
      which in turn blocks caspase-3 activation and inhibits cytochrome c release into
      the cytosol.

PMID- 12220329
TI  - Effects of pinealectomy on the levels and the circadian rhythm of plasma
      homocysteine in rats.
AB  - Hyperhomocysteinemia is an independent cardiovascular risk factor. There are
      several factors including aging that contribute to the development of
      hyperhomocysteinemia. Nevertheless, the exact mechanisms causing this condition
      are still debated. We hypothesize that the age-related decrease in melatonin
      levels may be consequential in hyperhomocysteinemia. Recently, we found that
      plasma homocysteine (Hcy) levels are increased in pinealectomized (PINX) rats and
      melatonin reverses this increase. The aim of the present study was to determine
      if there is a circadian rhythm of plasma Hcy in rats and to examine the effect of
      pinealectomy on this cycle. Plasma Hcy levels demonstrated a 24-hr rhythm with a
      peak at 02:00 hr and a nadir at 14:00 hr in both control and PINX rats.
      Pinealectomy did not change the phase of the rhythm or the nocturnal elevation of
      plasma Hcy, but it did significantly increase mean plasma Hcy levels compared
      with those in controls and in rats that were sham pinealectomized (sPINX) (P <
      0.05). Melatonin decreases plasma Hcy levels while causing an increase in total
      glutathione (tGSH). In conclusion, we speculate that decreasing levels of
      melatonin during aging lead to hyperhomocysteinemia and a decrease in tGSH and
      the latter may be one of the factors causing hyperhomocysteinemia in the elderly
      population.

PMID- 12220330
TI  - Melatonin inhibits insulin secretion and decreases PKA levels without interfering
      with glucose metabolism in rat pancreatic islets.
AB  - The effect of melatonin (0.1 microM) on freshly isolated islets from adult rats
      was investigated. Melatonin caused a marked decrease of insulin secretion by
      islets in response to glucose. The mechanism involved was then examined.
      Melatonin did not interfere with glucose metabolism as indicated by the
      measurement of glucose oxidation. However, the content of the protein kinase A
      (PKA) catalytic alpha-subunit was significantly decreased in islets exposed to
      melatonin for 1 hr in the presence of 8.3 mM glucose, whereas that of the protein
      kinase C (PKC) alpha-subunit remained unchanged. Melatonin also inhibited
      forskolin-induced insulin secretion, a well known activator of adenylate cyclase
      (AC) activity. This may explain the low content of insulin found in islets
      incubated in the presence of melatonin for 3 hr. In fact, 3',5' -cyclic adenosine
      monophosphate (cAMP), a product of AC activity, stimulates insulin synthesis.
      These findings led us to postulate that a down-regulation of the PKA signaling
      pathway may be the mechanism involved in the melatonin inhibition of the process
      of glucose-induced insulin secretion.

PMID- 12220331
TI  - Physiological and pharmacological concentrations of melatonin protect against
      cisplatin-induced acute renal injury.
AB  - Cisplatin [cis-diaminedichloroplatinum(II), CDDP] is a widely used antineoplastic
      drug. However, it has major side-effects such as acute tubular necrosis (ATN).
      There are a number of studies concerning the role of reactive oxygen radical
      species in the pathophysiology of CDDP-dependent ATN. Several antioxidant agents
      have been reported to prevent this side-effect but there is no study regarding
      the protective action of either physiological or pharmacological concentrations
      of melatonin. Melatonin, the chief secretory product of the pineal gland, is a
      direct free radical scavenger and indirect antioxidant. We investigated the
      effects of melatonin on CDDP-induced changes of renal malondialdehyde (MDA), a
      lipid peroxidation product, and blood urea nitrogen (BUN) and serum creatine
      (Cr). The morphological changes in kidney were also examined using light
      microscopy. The rats were divided into two groups: pinealectomized (Px) and sham
      operated (non-Px). Both CDDP and melatonin were administered to all groups. MDA
      levels were found to be higher in Px than non-Px animals. CDDP administration to
      Px or non-Px rats increased renal MDA levels and melatonin administration either
      before or after CDDP injection caused significant decreases in MDA in kidney
      compared with those in rats treated with CDDP alone. Serum levels of BUN and Cr
      did not change as a result of any treatment. Morphological tubule damage because
      of CDDP was more severe in the renal cortex than in the medulla. The damage to
      the kidney induced by CDDP was reversed by melatonin. The results show that
      pharmacological and physiological concentrations of melatonin reduce CDDP-induced
      renal injury.

PMID- 12220332
TI  - On the in vitro antioxidative properties of melatonin.
AB  - The aim of this study is to examine possible in vitro antioxidant effects of
      melatonin. Thus, the total in vitro antioxidant activity of melatonin was studied
      using a thiocyanate method. Additionally, the reducing power, the superoxide
      anion scavenging activity and free radical scavenging activity of melatonin were
      determined. Melatonin exhibited potent antioxidant activity in a linoleic acid
      emulsion system. The antioxidant activity increased with increasing
      concentrations of melatonin (50-500 microg). The 50, 100, 250 and 500 microg
      melatonin doses showed 41, 60, 86 and 99% inhibition of peroxidation of linoleic
      acid, respectively. On the other hand, a 500-microg dose of alpha-tocopherol
      showed 34% inhibition of peroxidation of linoleic acid. Like the total
      antioxidant activity, the reducing power of melatonin increased in a dose
      dependent manner. The reducing power of melatonin was statistically significant
      versus control, but lower than butylated hydroxytoluene (BHT) or quercetin.
      Additionally, melatonin had potent superoxide radical scavenging activity and
      exhibited a higher superoxide radical scavenging activity than quercetin or BHT
      but lower than butylated hydroxyanisole (BHA). Melatonin's direct free radical
      scavenging actions may account, at least in part, for its ability to reduce lipid
      peroxidation. Melatonin may have utility in protecting stored foods from free
      radical-induced deterioration.

PMID- 12220333
TI  - Daily rhythm of glucose-induced insulin secretion by isolated islets from intact
      and pinealectomized rat.
AB  - It is well known that pinealectomy induces in rats a diminished glucose
      tolerance, insulin resistance, a reduction in GLUT4 content in adipose and
      muscular tissues, a decrease in hepatic and muscular glycogenesis, impairment of
      glucagon action and an increase in blood pyruvate concentration. In addition, it
      has been shown that melatonin suppresses insulin secretion in several
      experimental conditions. The objective of the present study was to investigate
      the daily rhythm of glucose-induced insulin secretion and glucose oxidation by
      isolated pancreatic islets and to investigate the effect of chronic absence of
      melatonin (30 days of pinealectomy) on this rhythmic process. The data obtained
      confirmed the presence of a strong 24-hr rhythm of insulin secretion by isolated
      pancreatic islets. In addition, it was demonstrated that the glucose-metabolizing
      ability of the B-cell follows a daily rhythm phase locked to insulin secretion
      rhythm. Most interesting, however, was the demonstration that the daily rhythmic
      processes of insulin secretion and B-cell -[U-14C]-glucose oxidation by isolated
      pancreatic islets is completely modified by the chronic absence of the pineal
      gland. Thus, pinealectomy induced in all groups an increase in 24-hr mean glucose
      stimulated insulin secretion and [U-14C]-glucose oxidation, in addition to some
      alterations in the rhythmic amplitude and a remarkable phase-advancing of the
      daily curves for 8.3 mm glucose (a condition similar to that observed in fed
      animals and where the B-cells are supposedly more active). These observations
      strongly suggest that the presence of the pineal gland may be necessary for the
      proper synchronization of these metabolic rhythms with other circadian rhythms
      like activity-rest and feeding.

PMID- 12220334
TI  - Regulation of gene expression by melatonin: a microarray survey of the rat
      retina.
AB  - The pineal secretory product melatonin is synthesized by pinealocytes and retinal
      photoreceptors on a cyclic rhythm, with highest levels occurring at night. Our
      previous work has demonstrated that melatonin treatment increases the sensitivity
      of the rat retina to light-induced photoreceptor cell death. This raises the
      possibility that inappropriate exposure of photoreceptors to melatonin may result
      in visual impairment, caused by a loss of retinal photoreceptors. We hypothesize
      that retinal genes whose expression levels are altered in response to melatonin
      may be involved in processes that contribute to light-induced photoreceptor cell
      death. To identify retinal genes that are up- or down-regulated in response to
      melatonin receptor binding, rats were treated with or without melatonin, and the
      RNA from the neural retinas and retinal pigment epithelium (RPE) were analyzed
      for differential gene expression by hybridization of labeled cRNA probes to an
      Affymetrix rat genome microarray set. GeneChip algorithms were applied to
      measured hybridization intensities of compared samples and showed that in the
      neural retina, six genes were up-regulated, and eight were down-regulated. In the
      RPE, 15 genes were up-regulated, and two genes were down-regulated. The protein
      products of these specific genes are potentially involved in the molecular
      mechanism of melatonin action in the retina, and may play a role in the effect of
      melatonin on light-induced photoreceptor cell death. Identification of these
      candidate genes and their response to melatonin administration may provide a
      foundation for further studies on gene regulation by melatonin, the function of
      melatonin in the retina, and the role of circadian signaling in inherited and
      environmentally induced photoreceptor degenerations.

PMID- 12220335
TI  - Melatonin as a candidate compound for neuroprotection in amyotrophic lateral
      sclerosis (ALS): high tolerability of daily oral melatonin administration in ALS
      patients.

PMID- 12220336
TI  - Multidisciplinary examination of patients with illness attributed to dental
      fillings.
AB  - OBJECTIVE AND METHODS: In 1993, a special Amalgam Clinic was established at
      Huddinge University Hospital. Residents in the Stockholm County area with
      morbidity attributed to dental fillings ('amalgam disease'), were referred to
      this clinic. Patients were examined by a dentist (n 428), a physician (n 379),
      and a psychologist (n 360). Sixty-nine per cent were women and 31% men; the mean
      patient age was 46 years. RESULTS: Oral symptoms included tender or aching teeth
      (60%), metallic taste (54%), sore mouth (43%) and dry mouth (43%). Signs of
      moderate or severe temporomandibular joint dysfunction were found in 81 cases,
      glossitis in 30 and oral lichen in 26 cases. Common general symptoms included
      diffuse pain (78%), general weakness (75%), extreme fatigue (68%) and dizziness
      (68%). Seven per cent of the patients suffered from previously undiagnosed
      medical conditions (thyroid dysfunction, anaemia, cardiopathy, renal disease,
      cancer). In 26 subjects, skin patch testing revealed allergy to mercury, gold or
      palladium. The median concentration of mercury was 10 nmol L-1 in whole blood, 3
      nmol L-1 in plasma and 10 nmol L-1 in urine, i.e. normal levels. Earlier mental
      trauma was common, and in the psychological questionnaire SCL-90, clear
      tendencies to somatization were found. Only a few cases of severe psychiatric
      illness were observed. No positive correlation was found between the amount of
      amalgam and somatic symptoms or psychological effect parameters. CONCLUSIONS: The
      results do not support the hypothesis that release of mercury from amalgam
      fillings is the cause of 'amalgam disease', but suggest that there may be various
      explanations for the patient's complaints.

PMID- 12220337
TI  - Clinical and SEM evaluations of three compomer systems in Class V carious
      lesions.
AB  - The aim of this study was to evaluate the clinical performance of three compomer
      systems: Compoglass F, Dyract AP and F2000 in Class V carious lesions. In
      addition, some restorations were placed in teeth scheduled for extractions in
      order to evaluate the compomer/dentin interface with the scanning electron
      microscope (SEM). A total of 175 Class V carious lesions having the gingival
      margins extending into cementum were restored with the tested materials. Each
      restoration was clinically evaluated immediately after placement, after 1 year
      and after 2 years using the USPHS criteria. After 1 year no loss of restoration
      was recorded. No significant difference between the materials was observed for
      any evaluation category. After 2 years, one Compoglass and two Dyract
      restorations were lost. No loss of F2000 was reported. No significant difference
      was reported between the tested materials and between the 2-year data and
      baseline ones. A well-defined hybrid layer as well as resin tags was seen at the
      interface between the tested materials and vital dentin.

PMID- 12220338
TI  - Methodology of oral sensory tests.
AB  - Different methods of oral sensory tests including light touch sensation, two
      point discrimination, vibrotactile function and thermal sensation were compared.
      Healthy subjects were tested to assess the results obtained from two
      psychophysical approaches, namely the staircase and the ascending & descending
      method of limits for light touch sensation and two-point discrimination. Both
      methods appeared to be reliable for examining oral sensory function. The effect
      of topical anaesthesia was also evaluated but no conclusion could be drawn as too
      few subjects were involved. Newly developed simple testing tools for two-point
      discrimination and thermal sensation in a clinical situation were developed prior
      to this study and tested for their reproducibility. Thermal sensation could be
      reliably detected in repeated trials. Although the hand-held instruments have
      some drawbacks, the outcome of these instruments in a clinical environment is
      suitable for assessing oral sensory function. Three different frequencies (32,
      128 and 256 Hz) were used to estimate the vibrotactile function. Different
      threshold levels were found at different frequencies.

PMID- 12220339
TI  - Clinical relevance of a simple fragmentation model to evaluate human masticatory
      performance.
AB  - To explain the breakage process of food particles in human mastication, we
      propose a simple fragmentation model. To verify its clinical accuracy, a
      mechanical test with a sieving method and a natural test food (coffee) was
      performed on three groups of subjects. The values obtained permitted to
      demonstrate that the model could predict, at least qualitatively, the general
      trend of the experimental data, even for a very small group (two subjects). It
      also shows that the choice of the yielding factors used to calculate the
      masticatory index (MI) is relevant.

PMID- 12220340
TI  - Do early signs of orofacial dysfunctions and occlusal variables predict
      development of TMD in adolescence?
AB  - The aim of the present report was to focus on if early signs of different
      orofacial dysfunctions, e.g. misarticulations of speech, problems in oral motor
      skills and TMD, malocclusions or occlusal interferences could predict the
      development of temporomandibular disorders (TMD) in adolescence. Altogether there
      were 94 children referred for speech therapy and 93 controls who participated in
      all three stages of this longitudinal study. In the whole sample the mean age
      during the first examination was 7.6 years, during the second examination 10.6
      years, and during the third one 15.4 years. Multiple logistic regression models
      showed that subjects with a tendency to open bite tended to have palpatory
      tenderness of the muscles. Overjet was positively related to hypermobile but
      negatively to hypomobile jaw movements. Deviation on opening was associated with
      problems in oral motor skills, and some signs of TMD seemed to be related to each
      other. In addition, girls had a higher risk of having several signs of TMD than
      boys did. In conclusion, tendency to open bite, both mesial and distal molar
      occlusion and increased and decreased overjet were occlusal anomalies associated
      with TMD. Altogether, among 15-year-olds there seems to be both local and central
      factors in the aetiology of TMD.

PMID- 12220341
TI  - Effect of photo-irradiation on hardness of soft lining materials for denture
      base.
AB  - Nine photo-activated acrylic-type (EPL) soft lining materials were produced
      experimentally to examine their durability. The purpose of this study was to
      investigate the effect of photo-irradiation on the hardness of experimental soft
      lining materials. The hardness (Hex) of the nine EPLs was increased 4.3-170.1% by
      exposing them to light. The effect of irradiation on the Hex of the EPLs was
      remarkable when the material contained much ethylmethacrylate, together with
      smaller amounts of di-n-butyl phthalate. Moreover, the Hex tended to increase for
      EPLs in which the liquid portion contained less di-n-butyl phthalate or more
      ethanol (Et). The weight change ratio (Wc) was greater for EPL specimens
      containing less Et. The Wcs ranged from 0.118 to 0.661% after 8 weeks. These
      results showed that the Hexs of six of the EPLs were approximately equal to those
      of four commercially available soft lining materials, and these six EPLs may have
      properties favouring their use in clinical dentistry.

PMID- 12220342
TI  - Effect of HEMA on bonding of Er:YAG laser-irradiated bovine dentine and 4
      META/MMA-TBB resin.
AB  - The purpose of this study was to evaluate the priming effect of 2
      hydroxyethylmetaclirate (HEMA) following acid treatment on resin bonding to
      prototype Er:YAG laser-irradiated dentine. Extracted bovine dentine following
      laser irradiation was acid treated by aqueous solution of 10% citric acid (10-0)
      or 10% citric acid/3% ferric chloride (10-3), and additionally treated with 35%
      HEMA. Pre-treated dentines were bonded to the polymethyl-methacrylate (PMMA) rod
      with 4-META/MMA-TBB resin (Super Bond C & B) and miniaturized dumbbell-shaped
      bonded specimens were prepared. These specimens profiled for tensile bond testing
      and fractured surfaces were observed by scanning electron microscopy (SEM). Cross
      sections of resin-dentine interface were also examined. The HEMA treatment
      following acid conditioned by 10-3 or 10-0 for both laser-irradiated and non
      irradiated dentines was significantly higher than that without HEMA treatment.
      SEM view of a fractured specimen showed some cohesive failure in cured resin, but
      almost all of the fractured surface shows boundary failure between the penetrated
      resin and underlying dentine. A cross-sectional view of the interface showed a
      very thick hybrid layer between the hybridized dentine and underlying dentine. It
      was concluded that HEMA treatment following acid conditioning provided a slightly
      higher bond strength for both the Er:YAG laser-irradiated and non-irradiated
      dentines. However, the bond strength of Er:YAG laser irradiated dentine was
      significantly lower than that of the non-irradiated dentine.

PMID- 12220343
TI  - Wear of three dental composites under different testing conditions.
AB  - Although a great effort has been made to date with research on in vitro wear
      simulation testing, it is difficult to identify the relationship between the
      results of in vitro testing and in vivo observations. An intensive study into
      wear mechanisms is necessary for wear testing simulation. The objective of this
      research was to study the wear behaviour of three selected dental composites
      under different wear conditions to provide a more rational explanation for their
      wear mechanisms. Two typical wear conditions, two- and three-body wear, were
      conducted on the composites. The results showed that the wear losses had
      different rankings between two wear conditions. It is therefore unreliable to
      predict the clinical performance merely by wear loss ranking from in vitro wear
      testing. Further analysis on the wear surfaces indicated that three dental
      composites experienced different wear mechanisms under different wear conditions.
      It is concluded that in vitro analysis of wear mechanisms may lead to a better
      understanding of in vivo failure patterns. Similar wear mechanisms should be the
      premise for any correlation between the results of in vitro and in vivo studies.

PMID- 12220344
TI  - The expression of tenascin mRNA in human temporomandibular joint specimens.
AB  - The expression of mRNA of tenascin in the temporomandibular joint (TMJ) disc and
      synovial membrane was examined in 20 human TMJ samples from patients with
      internal derangement of the TMJ and 10 control specimens by in situ hybridization
      technique using paraffine-embedded tissue, and antisense and sense cRNA probes.
      In control specimens, tenascin mRNA was not expressed. However, we were able to
      find tenascin mRNA expression in the surgical specimens. In 15 of 20 samples,
      ranging numbers of synovial cells expressed tenascin mRNA in the hypertrophic
      synovial membranes. Also, in 6 of 20 samples, tenascin mRNA was identified in
      fibroblasts. In four specimens, vascular endothelial cells were positive for the
      mRNA. In internal derangement cases, histopathological findings are often found
      such as synovitis, new capillary growth and fibrosis. The present study
      demonstrates that tenascin is produced specifically in synovial cells, vascular
      endothelial cells and fibroblasts affected in the portion of TMJ with internal
      derangement.

PMID- 12220345
TI  - Effect of ethanol on the hardness and relaxation modulus of experimental photo
      activated soft lining materials stored in aqueous solutions.
AB  - We studied changes in the hardness, relaxation modulus [Er(t)], and weight change
      ratio (Wc) of experimental photo-activated acrylic soft lining materials (EPLs)
      stored in three aqueous solutions [distilled water (DW), physiological saline
      solution (PS), and artificial saliva (AS)] at 37 degrees C for 8 weeks. The
      hardness of the EPLs increased markedly during the first 4 days of storage, and
      subsequently changed little. The greatest hardness occurred in the EPL specimen
      containing the largest amount of ethanol (Et). The relaxation modulus [Er(8)] of
      the EPLs ranged from 1.35 to 1.66 MPa immediately before storage, and from 1.43
      to 2.21 MPa after an 8-week immersion. Like hardness, the increase in [Er(t)] was
      greatest when the EPL contained large amounts of Et. The Wc ranged from 0.118 to
      0.661% after storage for 8 weeks, and increased most for the EPL specimen
      containing the smallest amount of Et. Furthermore, 3-7 days after the start of
      immersion many hollows were observed in the surface of specimens with a high Et
      content. The results indicate that Wc and hollow formation are sensitive to the
      Et content of the EPL, and that Et content is closely tied to the change in
      hardness and relaxation modulus with time.

PMID- 12220346
TI  - Bond strength of five current adhesives to caries-affected dentin.
AB  - Five current dentin adhesives were evaluated for their ability to bond to caries
      affected dentin. The materials were: total etch [Solid Bond (SB)], two self-etch
      [Clearfil SE Bond (CSE), Etch and Prime (EP)], two one bottle [Prime and Bond 2.1
      (PB), One Coat Bond (OCB)]. Sixty extracted molar teeth with proximal caries
      (mesial or distal) extending into mid-dentin were used. By grinding normal and
      caries-affected proximal surfaces, flat dentin surfaces were obtained. The
      surfaces were then bonded with each adhesive system and composite resins were
      added to the surfaces by packing the material into a cylindrical-shaped plastic
      matrix with an internal diameter of 2.5 mm and height of 3 mm. Shear bond testing
      was performed following 10 days incubation of specimens in distilled water at 37
      degrees C. Results were analysed by Kruskal-Wallis ANOVA, and Mann-Whitney U
      multiple comparison test and Wilcoxon rank tests. The results obtained with CSE,
      SB, and EP were similar in caries affected and normal dentin (P > 0.05). But
      bonds made to normal dentin with OCB and PB were lower (P < 0.05) than bonds to
      caries-affected dentin. Bonding to caries-affected dentin with CSE (24.49 +/-
      5.38), SB (21.49 +/- 9.15), and EP (21.19 +/- 9.17) showed shear bond strengths
      higher than OCB (17.43 +/- 9.78) and PB (14.10 +/- 7.94) (P < 0.05). Bonding to
      normal dentin with CSE (29.91 +/- 8.95) was the highest (P < 0.05). SB (21.17 +/-
      5.41) and EP (17.45 +/- 6.21) showed shear bond strengths higher than OCB (11.99
      +/- 10.15) and PB (10.57 +/- 4.56) (P < 0.05).

PMID- 12220347
TI  - Photopolymerization of composite resins with plasma light.
AB  - Everyday improvements in components and characteristics of composite materials
      have induced faster development of curing units. Besides standard halogen curing
      units and soft-start photopolymerization light sources, some experiments with
      argon and pulsed laser light and low intensity blue superbright light emitting
      diodes have been made. On the other hand, rapid polymerization with strong plasma
      light is also clinically applicable. The aim of this study was to measure the
      degree of conversion and temperature rise for three restorative composite
      materials: Tetric Ceram (Vivadent, Schaan, Liechtenstein), Pertac II (ESPE,
      Seefeld, Germany) and Z100 (3M Dental Products, St Paul, MN, USA) during
      polymerization with plasma light Apollo 95E (DMDS, Dental/Medical Diagnostic
      Systems, Fleury d'Aude, France) and compare it with the results of polymerization
      with a halogen curing unit, Elipar Trilight (ESPE, Seefeld, Germany). The results
      revealed the degree of conversion values in the case of polymerization with
      plasma light to be almost equal to those obtained by curing with the halogen
      curing unit, whereas the temperature rise was almost negligible.

PMID- 12220348
TI  - Effect of cooling procedure on final denture base adaptation.
AB  - Well-fitted dentures prevent hyperplasic lesions, provide chewing efficiency and
      promote patient's comfort. Several factors may affect final adaptation of
      dentures, as the type of the acrylic resin, the flask cooling procedure and the
      water uptake. This investigation evaluated the effect of water storage and two
      different cooling procedures [bench cooling (BC) for 2 h; running water (RW) at
      20 degrees C for 45 min] on the final adaptation of denture bases. A heat-cured
      acrylic resin (CL, Classico, Classico Artigos Odontologicos) and two microwave
      cured acrylic resins [Acron MC, (AC) GC Dent. Ind. Corp.; Onda Cryl (OC),
      Classico Artigos Odontologicos] were used to make the bases. Adaptation was
      assessed by measuring the weight of an intervening layer of silicone impression
      material between the base and the master die. Data was submitted to ANOVA and
      Tukey's test (0.05). The following means were found: (BC) CL=0.72 +/- 0.03 a;
      AC=0.70 +/- 0.03 b; OC=0.76 +/- 0.04 c//(RW) CL= 1.00 +/- 0.11 a; AC=1.00 +/-
      0.12 a; OC=0.95 +/- 0.10 a. Different labels join groups that are not
      statistically different (P > 0.05). Comparisons are made among groups submitted
      to the same cooling procedure (BC or RW). The conclusions are: interaction of
      type of material and cooling procedure had a statistically significant effect on
      the final adaptation of the denture bases (P < 0.05); water storage was not
      detected as a source of variance (P > 0.05) on the final adaptation.

PMID- 12220349
TI  - Fluoride release and uptake characteristics of aesthetic restorative materials.
AB  - The aims of this study were firstly to investigate the fluoride-releasing
      characteristics of two composite resins (Tetric and Valux Plus), two polyacid
      modified resin composites (Compoglass and Dyract), and conventional glass-ionomer
      cement (Ceramfil beta). The second aim was to assess the fluoride uptake and
      subsequent release from the same range of materials. Fifteen discs (6 mm diameter
      and 1.5 mm height) were prepared for each material. Each disc was immersed in 4
      ML of deionized water within a plastic vial. The release of fluoride was measured
      daily at 1, 2, 3, 4, 5, 15, 30 and 60 days. After daily fluoride release was
      measured for 60 days, samples were refluoridated in 1000-ppm sodium fluoride
      (NaF) solutions (pH 6.6) for 10 min and fluoride release was measured daily for a
      total of 5 days. The release of fluoride from aesthetic restorative materials was
      measured by using specific fluoride electrode and an ionanalyser. Results were
      statistically analysed by two-way repeated measure ANOVA and Duncan's multiple
      range test. The results revealed that all fluoride-containing materials (Ceramfil
      beta, Compoglass, Dyract, Tetric) released fluoride initially and the release was
      greatest at the first day. At any time during the test period Ceramfil beta
      released the most and Valux Plus did not release any detectable fluoride (P <
      0.01). Sample exposures to 1000 ppm NaF solution increased the 24-h fluoride
      release from all fluoride-containing materials. This difference lasted only 24-48
      h after exposure. Ceramfil beta had a tendency to recharge not seen with the
      other materials (P < 0.05).

PMID- 12220350
TI  - DNA methylation: an epigenetic pathway to cancer and a promising target for
      anticancer therapy.
AB  - The unique properties of a cancer cell are acquired through a stepwise
      accumulation of heritable changes in the information content of proto-oncogenes
      and tumor suppressor genes. While gain, loss, and mutation of genetic information
      have long been known to contribute to tumorigenesis, it has been increasingly
      recognized over the past 5 years that 'epigenetic' mechanisms may play an equally
      important role. The main epigenetic modification of the human genome is
      methylation of cytosine residues within the context of the CpG dinucleotide. De
      novo methylation of 'CpG islands' in the promoter regions of tumor suppressor
      genes may lead to transcriptional silencing through a complex process involving
      histone deacetylation and chromatin condensation, and thus represents a
      tumorigenic event that is functionally equivalent to genetic changes like
      mutation and deletion. DNA methylation is interesting from a diagnostic viewpoint
      because it may be easily detected in DNA released from neoplastic and
      preneoplastic lesions into serum, urine or sputum, and from a therapeutic
      viewpoint because epigenetically silenced genes may be reactivated by inhibitors
      of DNA methylation and/or histone deacetylase. A better understanding of
      epigenetic mechanisms leading to tumor formation and chemoresistance may
      eventually improve current cancer treatment regimens and be instructive for a
      more rational use of anticancer agents.

PMID- 12220351
TI  - Deranged expression of the E-cadherin/beta-catenin complex and the epidermal
      growth factor receptor in the clinical evolution and progression of oral squamous
      cell carcinomas.
AB  - BACKGROUND: Deranged expression and function of the E-cadherin/beta-catenin (E
      cad/beta-cat) complex and the epidermal growth factor receptor (EGFR) have been
      implicated in the development and progression of carcinomas. METHODS: To estimate
      the role of these molecules in oral cancer, we investigated 75 primary oral
      squamous cell carcinomas (OSCCs) with adjacent normal and/or dysplastic mucosa,
      30 paired metastases and 12 recurrences by immunohistochemistry. RESULTS: All
      three molecules were constitutionally expressed in the basal/parabasal layers of
      tumour adjacent 'normal' epithelium, in contrast to a significant increase of
      EGFR and heterogeneous expression of E-cad/beta-cat in dysplasia. In OSCCs, over
      expression of EGFR correlated significantly with lower tumour grade and poor
      prognosis, loss of E-cad was a significant marker for shortened survival, reduced
      beta-cat staining was a predictive marker for lymph node metastasis. CONCLUSIONS:
      There is a perturbance in intercellular adhesion molecules and EGFR
      expression/function in oral cancer with major clinical impact. E-cad and beta-cat
      seem to inhibit EGFR to enhance the progression of OSCCs.

PMID- 12220352
TI  - Expression of type 2 nitric oxide synthase and p53 in Warthin's tumour of the
      parotid.
AB  - Although the pathogenesis of Warthin's tumour is not fully understood, it is
      generally thought that the tumour arises from heterotopic salivary ducts within
      pre-existing lymphoid tissue. Prolonged nitric oxide (NO) production by the
      enzyme type 2 nitric oxide synthase (NOS2) has been implicated in the
      pathogenesis of many solid tumours, but not in Warthin's tumour. Since NO and
      NOS2 are known to be associated with p53, the immunohistochemical expression of
      both NOS2 and p53 was investigated in 23 cases of Warthin's tumour. Widespread
      diffuse cytoplasmic immunostaining for NOS2 was found in tumour epithelial cells
      of all 23 cases studied, and it was additionally expressed in normal salivary
      duct epithelium. p53 staining was localised to the nuclei of tumour epithelium in
      16 cases, with a similar pattern of distribution to tumour NOS2 expression. A
      significant correlation was found between NOS2 and p53 staining in the tumours (P
      < 0.001). In contrast to NOS2, p53 was not expressed by normal salivary ductal
      cells in any of the cases studied. NOS2 is widely expressed by the tumour
      epithelium of Warthin's, and its association with p53 expression is discussed.
      The role of NO in the pathogenesis of Warthin's tumour remains to be established.

PMID- 12220353
TI  - HER2/neu expression in adenoid cystic carcinoma of salivary gland origin: an
      immunohistochemical study.
AB  - BACKGROUND: Adenoid cystic carcinoma (ACC) is a malignant tumor of salivary gland
      origin, which is characterized by a high rate of local recurrence and distant
      hematogenous metastasis. Despite aggressive surgical treatment and radiotherapy,
      the patient's long-term prognosis is dismal. Prompted by recent studies on the
      amplification of the oncogene HER2/neu in salivary gland tumors, we analyzed the
      immunohistochemical overexpression of HER2/neu in salivary glands ACC. If the
      tumor exhibits overexpression of HER2/neu, then treating it with the anti
      HER2/neu therapeutic agent, Herceptin (Trastuzumab, Genentech, CA), could be
      considered. METHODS: The study comprised of 32 samples of formalin-fixed,
      paraffin-embedded specimens. All laboratory procedures and scoring criteria were
      performed according to currently approved FDA methods. RESULTS: HER2/neu
      overexpression was found in only five (16%) cases. Four cases (13%) scored 1+ and
      one case (3%) scored 2+. CONCLUSIONS: The low prevalence of HER2/neu
      overexpression in ACC limits the clinical utility of Herceptin therapy for
      salivary gland ACC.

PMID- 12220354
TI  - Betel quid-associated oral lesions and oral Candida species in a female Cambodian
      cohort.
AB  - BACKGROUND: Betel quid chewing (BQC) is still prevalent among elderly Cambodian
      women and is associated with a wide variety of oral mucosal lesions. BQC has also
      been associated with a reduced rate of dental caries and changes in the oral
      microbiological flora. METHODS: Since no studies were available on the impact of
      BQC on the oral carriage of Candida species, in this study oral swabs
      (Fungiquick, Hain Diagnostika, Germany) were taken from the tongue and palate of
      48 Cambodian women with BQC habit (study group) and 13 control subjects without
      BQC habit (control group) to determine the spectrum of Candida species in these
      two groups. In addition, we investigated lesions of the oral mucosa likely to be
      associated with BQC habit in both study and control groups. RESULTS: The median
      duration of BQC was 10 years (range 10 months-30 years). The following oral
      lesions were found in the study group: betel chewer's mucosa (85.4%), oral
      leukoplakia (8.3%), leukoedema (37.5%) and oral lichen planus (4.2%). Oral
      candidiasis was seen neither in BQ-chewers nor in controls. Candida spp. were
      found in 70.8% of the cases (controls 69.2%). Whilst C. albicans was isolated
      from 27.1% of the study cohort, C. tropicalis was the second most common isolate.
      One control case was colonised by C. dubliniensis--the first report of this
      organism from a Cambodian population. There was no significant difference in the
      candidal carriage rate or the Candida species isolated between the study and the
      control group. CONCLUSIONS: Mycological findings from the present study do not
      indicate that BQC has a significant effect on oral colonisation by Candida
      species.

PMID- 12220356
TI  - Elemental sulphur and alkali elutable melanin detected in oral melanosis and
      malignant melanoma by energy-filtering transmission electron microscopy.
AB  - BACKGROUND: The morphology and contents of melanosomes are important features for
      differentiating melanocyte-derived melanotic lesions such as melanosis and
      malignant melanoma. METHODS: In this study, we attempted to elucidate the
      structure of melanin and sulphur content in oral melanosis and malignant
      melanomas by ultrastructural analysis. RESULTS: In oral melanosis, the essential
      pathological findings were overproduction of eumelanin and discharge of melanin
      into keratinocytes. In malignant melanoma in situ, pleomorphic and ellipsoid
      abnormal melanosomes with an increase in sulphur content and alkali elution rate
      were detected. In invasive malignant melanoma, the irregular ellipsoid and
      spheroid melanosomes existing either as discrete bodies or compound melanosomes
      with furtherly increased sulphur content and alkali elution were detected.
      CONCLUSIONS: Our findings suggest that abnormal melanosome morphology and high
      sulphur content are predictive markers for assessment of early or precancerous
      melanotic lesions and malignant melanoma.

PMID- 12220355
TI  - Effect of home bleaching and smoking on marginal gingival epithelium
      proliferation: a histologic study in women.
AB  - BACKGROUND: Animal studies have suggested that home bleaching agents can cause
      morphological alterations and changes in the proliferative rate of oral
      epithelium. METHODS: A bleaching agent containing 10% carbamide peroxide with
      carbopol was used in 11 women (five smokers and six non-smokers) during a 5-week
      period. Two biopsies were performed, one of them 15 days before the beginning of
      the home bleaching treatment and the other immediately after the 5-week bleaching
      treatment. Two analyses were performed in the histological sections obtained from
      the biopsies: epithelium morphometry and assessment of the epithelium's
      proliferative activity by proliferating cell nuclear antigen (PCNA)
      immunohistochemistry. RESULTS: The home bleaching agent increases epithelium
      thickness and the PCNA index in both smoker and non-smoker patients. CONCLUSION:
      Carbamide peroxide (10%) caused an augmentation in the proliferative activity
      within the basal and parabasal layers of the gingival epithelium, resulting in a
      change in this tissue's morphometry.

PMID- 12220357
TI  - Expression of inducible nitric oxide synthase and heat shock proteins in
      periapical inflammatory lesions.
AB  - BACKGROUND: The mechanisms responsible for activation and proliferation of lining
      epithelium involved in inflammatory processes in periapical inflammatory lesions
      remain unclear. In this study, the expression and distribution of inducible
      nitric oxide synthase (iNOS) and heat shock proteins (HSPs) were
      immunohistochemically investigated in periapical inflammatory lesions. METHODS:
      Control specimens of periodontal ligaments including Malassez epithelial rests
      from seven teeth and periapical inflammatory lesions (15 apical granulomas (AGs),
      16 radicular cysts (RCs), and 10 residual radicular cysts (RRCs)) were prepared
      and examined by the standard streptavidin-biotin peroxidase complex method using
      anti-iNOS rabbit polyclonal antiserum, and anti-HSP27, -HSP60, -HSP70 mouse
      monoclonal antibodies. RESULTS: Immunoreactivity for iNOS was detected in
      macrophages, lymphocytes, and endothelial cells of granulation tissue and in
      lining epithelium of periapical inflammatory lesions. Malassez epithelial rests
      showed no or slight staining for iNOS. The epithelial staining intensity of iNOS
      in RCs was greater than that in Malassez epithelial rests and RRCs.
      Immunoreactivity for HSP27 was recognized in inflammatory cells, endothelial
      cells and lining epithelium of periapical inflammatory lesions and in Malassez
      epithelial rests. HSP60 was detected in some lymphocytes of granulation tissue
      and in lining epithelium of periapical inflammatory lesions, whereas Malassez
      epithelial rests showed no staining for HSP60. Epithelial HSP60 reactivity was
      more intense in RCs than in RRCs. HSP70 was expressed in lymphocytes, endothelial
      cells and lining epithelium of periapical inflammatory lesions and in Malassez
      epithelial rests. The staining intensity of HSP70 in Malassez epithelial rests
      was slightly lower than that in lining epithelium of RCs and RRCs. CONCLUSIONS:
      These data demonstrate that the expressions of iNOS, HSP60, and HSP70 are
      involved in inflammatory processes and might play a role in the activation and
      proliferation of lining epithelium, leading to progression of periapical
      inflammatory lesions.

PMID- 12220359
TI  - Odontogenic cyst with verrucous proliferation.
AB  - An unusual case of an odontogenic cyst with verrucous proliferation is described
      in a 13-year-old girl. This histologically distinctive odontogenic cyst variant
      does not appear to have been reported previously. The cyst was characterised by a
      series of verrucous projections in the lumen with hypergranulosis and cells
      resembling koilocytes, raising the possibility of a viral aetiology. However, no
      evidence of human papillomavirus (HPV) was found using immunohistochemistry and
      polymerase chain reaction (PCR) amplification.

PMID- 12220358
TI  - Distribution of basement membrane type IV collagen alpha chains in ameloblastoma:
      an immunofluorescence study.
AB  - BACKGROUND: Type IV collagen, a heterotrimeric molecule that exists in six
      genetically distinct forms, alpha1(IV)-alpha6(IV) is a major structural component
      of basement membrane (BM) and acts as a scaffold for other BM constituents.
      METHODS: Indirect immunofluorescence using alpha chain-specific monoclonal
      antibodies was employed to clarify basement membrane (BM) collagen IV
      distribution in two ameloblastoma, and for comparison, on oral mucosa and tooth
      germ. RESULTS: Ameloblastoma BM expressed five of six genetically distinct forms
      of collagen IV: alpha1(IV), alpha2(IV), alpha5(IV) and alpha6(IV) chains occurred
      as intense linear stainings without disruption around neoplastic epithelium, and
      this expression pattern was fundamentally similar to oral mucosa BM; alpha4(IV)
      expression was rare and occurred around nests of primitive tumor cells or
      potentially invasive sites. The tooth germ demonstrated a stage- and position
      specific collagen IV distribution: the inner enamel epithelium BM expressed
      alpha1(IV), alpha2(IV), and alpha4(IV) except in the cuspal predentine region;
      and the outer enamel epithelium BM expressed alpha1(IV), alpha2(IV), alpha5(IV),
      and alpha6(IV) chains. CONCLUSIONS: Results suggest that collagen IV alpha chain
      distribution in ameloblastoma BM plays an important role in tumor
      cytodifferentiation and progression.

PMID- 12220362
TI  - A national survey of physician practices regarding influenza vaccine.
AB  - OBJECTIVE: To characterize U.S. physicians' practices regarding influenza
      vaccine, particularly regarding the capacity to identify high-risk patients, the
      use of reminder systems, and the typical period of administration of vaccine.
      DESIGN: Cross-sectional mail survey administered in October and November 2000.
      PARTICIPANTS: National random sample of internists and family physicians (N =
      1,606). RESULTS: Response rate was 60%. Family physicians are significantly more
      likely than internists to administer influenza vaccine in their practices (82% vs
      76%; P <.05). Eighty percent of physicians typically administer influenza vaccine
      for 3 to 5 months, but only 27% continue administering vaccine after the typical
      national peak of influenza activity. Only one half of physicians said their
      practices are able to generate lists of patients with chronic illnesses at high
      risk for complications of influenza, and only one quarter had used mail or
      telephone reminder systems to contact high-risk patients. Physicians working in a
      physician network (including managed care organizations) are more than twice as
      likely to use reminders as physicians in other practice settings (odds ratio,
      2.04; 95% confidence interval, 1.17 to 3.55). CONCLUSIONS: Over three quarters of
      U.S. internists and family physicians routinely administer influenza vaccine, but
      few continue immunization efforts past the typical national peak of influenza
      activity. Many physicians may be limited by their practice data systems' capacity
      to identify high-risk patients. Despite the known effectiveness and cost
      effectiveness of reminder systems, few physicians use reminders for influenza
      vaccination efforts. These findings raise concerns about meeting domestic
      influenza vaccination goals-especially for individuals with chronic illness and
      during periods of delayed vaccine availability-and the possibility of increased
      morbidity and mortality attributable to influenza as a result.

PMID- 12220361
TI  - Vitamin D deficiency and secondary hyperparathyroidism are common complications
      in patients with peripheral arterial disease.
AB  - OBJECTIVE: To investigate via the vitamin D status whether patients with
      peripheral arterial disease (PAD) tend to develop vitamin D deficiency that in
      turn influences their clinical symptoms. DESIGN: Cross-sectional. SETTING:
      University hospital. PATIENTS AND PARTICIPANTS: Three hundred twenty-seven
      patients were evaluated; subjects with secondary causes of bone disease or bone
      active medication were excluded. One hundred sixty-one patients with either PAD
      stage II (n = 84) or stage IV (n = 77) were enrolled and compared to 45 age- and
      sex-matched healthy controls. MEASUREMENTS AND MAIN RESULTS: All patients
      underwent determinations of serum chemistry, 25-hydroxyvitamin D (vitamin D3)
      intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), and osteocalcin
      and were further stratified according to an individual restriction score into 3
      groups: mildly, moderately, or severely restricted in daily life due to the
      underlying disease. Patients with PAD IV showed significantly lower vitamin D3 (P
      =.0001), and calcium (P =.0001) values and significantly higher iPTH (P =.0001),
      osteocalcin (P =.0001) and ALP (P =.02) levels as compared to patients with PAD
      II. Patients considering themselves as severely restricted due to the underlying
      disease showed lower vitamin D3 and higher iPTH levels than those who described
      only a moderate (vitamin D3: P <.001; iPTH: P <.01) or mild (vitamin D3: P <.001;
      iPTH: P <.001) restriction in daily life. CONCLUSION: Patients with PAD IV,
      especially those who feel severely restricted due to the disease, are at high
      risk of developing vitamin D deficiency, secondary hyperparathyroidism, and
      ultimately osteomalacia due to immobilization and subsequent lack of exposure to
      sunlight, all of which in turn lead to further deterioration. Monitoring of
      vitamin D metabolism and vitamin D replacement therapy could be a simple,
      inexpensive approach to mitigating clinical symptoms and improving quality of
      life in patients with advanced PAD.

PMID- 12220363
TI  - HIV-seropositive individuals' optimistic beliefs about prognosis and relation to
      medication and safe sex adherence.
AB  - OBJECTIVE: The study objective was to characterize respondents' prognostic
      perceptions of HIV infection and to explore how perceptions might affect
      medication and safe sex nonadherence. METHODS: Surveys were mailed to 295 clients
      of an HIV-specific case management organization. Participants were asked to
      describe experience with HIV/AIDS right after serostatus knowledge and currently,
      using provided word lists, after which they were asked to assess current life
      expectancy. Self-reported information on antiretroviral medication and safe sex
      nonadherence was obtained. RESULTS: A total of 220 (75%) clients (66% nonwhite,
      73% male, 63% gay/bisexual, 50% educated >12 years, and 53% with incomes
      <$10,000/year) returned surveys. Negative descriptors from word lists were
      significantly less common and positive descriptors significantly more common now
      compared to right after serostatus knowledge. Current perceptions about life
      expectancy indicated that most respondents thought they would live many years,
      many believing they would live well into old age. Whites (odds ratio [OR], 0.34;
      P =.01) were less likely and those with >12 years education (OR, 2.76; P =.02)
      and with CD4 cell counts >200 (OR, 2.70; P =.01) were more likely to have
      optimistic prognostic beliefs. The optimistic subgroup, when compared with the
      pessimistic subgroup, was more likely to report medication (26% vs 13%, P =.04)
      and safe sex (57% vs 29%, P =.004) nonadherence. CONCLUSIONS: Seropositive
      individuals, including persons of color (adjusted) as well as women and drug
      users (unadjusted), self-reported optimistic beliefs about their prognosis. Those
      with more optimism about their prognosis were significantly more likely to report
      medication and safe sex nonadherence. A better understanding of seropositive
      patients' prognostic beliefs and the factors determining them is warranted.

PMID- 12220364
TI  - Accuracy of history, wheezing, and forced expiratory time in the diagnosis of
      chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To determine the accuracy of the history and selected elements of the
      physical examination in the diagnosis of chronic obstructive pulmonary disease
      (COPD). DESIGN: Independent blind comparison of the standard clinical examination
      (evaluating the accuracy of history, wheezing, and forced expiratory time [FET])
      with spirometry. The gold standard for diagnosis of COPD was a forced expiratory
      volume at 1 second (FEV1) below the fifth percentile (adjusted for patient height
      and age). SETTING: Seven sites in 6 countries, including investigators from
      primary care and secondary care settings. PARTICIPANTS: One hundred sixty-one
      consecutive patients with varying severity of disease (known COPD, suspected
      COPD, or no COPD) participated in the study. MAIN RESULTS: One hundred sixty-one
      patients (mean age 65 years, 39% female, 41% with known COPD, 27% with suspected
      COPD, and 32% normal) were recruited. Mean (+/-SD) FEV1 and forced vital capacity
      were 1,720 (+/-830) mL and 2,520 (+/-970) mL. The likelihood ratios (LR) for the
      tested elements of the clinical examination (and their P values on chi2 testing)
      were: self-reported history of COPD, 5.6 (P <.001); FET greater than 9 seconds,
      6.7 (P < 0.01); smoked longer than 40 pack years, 3.3 (P =.001); wheezing, 4.0 (P
      <.001); male gender, 1.6 (P <.001); and age over 65 years, 1.6 (P =.025). The
      accuracy of these elements was not appreciably different when reference standards
      other than FEV1 below the 5th percentile were applied. Only 3 elements of the
      clinical examination were significantly associated with the diagnosis of COPD on
      multivariate analysis: self-reported history of COPD (adjusted LR 4.4), wheezing
      (adjusted LR 2.9), and FET greater than 9 seconds (adjusted LR 4.6). Area under
      the receiver operating characteristic curve for the model incorporating these 3
      factors was 0.86. CONCLUSIONS: Less emphasis should be placed on the presence of
      isolated symptoms or signs in the diagnosis of COPD. While numerous elements of
      the clinical examination are associated with the diagnosis of COPD, only 3 are
      significant on multivariate analysis. Patients having all 3 of these findings
      have an LR of 33 (ruling in COPD); those with none have an LR of 0.18 (ruling out
      COPD).

PMID- 12220365
TI  - Physicians' preferences for active-controlled versus placebo-controlled trials of
      new antihypertensive drugs.
AB  - OBJECTIVE: To evaluate physicians' preferences for referring patients to, and
      using information from, active-controlled trials (ACTs) versus placebo-controlled
      trials (PCTs) of new antihypertensive drugs. DESIGN AND SETTING: Nationwide
      mailed survey, with telephone contact of nonresponders to assess nonresponse
      bias. PARTICIPANTS: One thousand two hundred primary care physicians randomly
      selected from the American Medical Association's Master File. Of 1,154 physicians
      eligible to respond, 651 (56.4%) returned completed questionnaires. MEASUREMENTS
      AND MAIN RESULTS: We measured physicians' stated willingness to encourage
      hypertensive patients to enroll in ACTs and PCTs of new antihypertensive drugs,
      their views of the relative merits of ACTs versus PCTs, their stated willingness
      to prescribe new drugs tested in ACTs or PCTs, and their views regarding the
      overall justifiability of the 2 designs. Physicians were significantly more
      likely to indicate they would encourage their patients to enroll in ACTs than in
      PCTs (P <.0001). Physicians thought ACTs provided more valuable information for
      their practices, were more likely to lead to a public health benefit, offered
      enrolled patients greater opportunity for personal benefit, and were less likely
      to expose enrolled patients to unnecessary risks (all P <.0001). Physicians were
      more likely to prescribe new drugs that had been compared in ACTs (P <.0001), and
      viewed ACTs as a more justifiable method for testing new antihypertensive drugs
      (P <.0001). There was no evidence of nonresponse bias for these main results.
      CONCLUSIONS: Although PCTs remain the standard method for testing new
      antihypertensive drugs, physicians strongly prefer ACTs. Using ACTs to test new
      antihypertensive drugs may enhance the efficiency of patient recruitment and more
      strongly influence physicians' prescribing practices.

PMID- 12220366
TI  - Racial, ethnic, and affluence differences in elderly patients' use of teaching
      hospitals.
AB  - OBJECTIVE: To understand the role of race, ethnicity, and affluence in elderly
      patients' use of teaching hospitals when they have that option. METHODS: Using a
      novel data set of 787,587 Medicare patients newly diagnosed with serious illness
      in 1993, we look at how sociodemographic factors influence whether patients use a
      teaching hospital for their initial hospitalization for their disease. We use
      hierarchical linear models to take into account differences in the availability
      of teaching hospitals to different groups. These models look within groups of
      people who live in the same county and ask what demographic factors make an
      individual within that county more or less likely to use a teaching hospital.
      RESULTS: We find that blacks are much more likely than whites to use teaching
      hospitals (odds ratio [OR], 1.75; 95% confidence interval [95% CI], 1.73 to
      1.77). However, Hispanics and Asian-Americans are less likely to use teaching
      hospitals than are whites (Hispanic OR, 0.92; 95% CI, 0.88 to 0.97; Asian
      American OR, 0.89; 95% CI, 0.82 to 0.97). Medicaid patients are less likely to
      use teaching hospitals (given their opportunities) than are non-Medicaid
      recipients (OR, 0.91; 95% CI, 0.90 to 0.92). And we find a curvilinear
      relationship with affluence, with those in the poorest and those in the
      wealthiest neighborhoods most likely to use a teaching hospital. CONCLUSION: The
      use of teaching hospitals is more complex that heretofore appreciated.
      Understanding why some groups do not go to teaching hospitals could be important
      for the health of those groups and of teaching hospitals.

PMID- 12220367
TI  - Teaching pre-clinical medical students an integrated approach to medical
      interviewing: half-day workshops using actors.
AB  - Teaching medical students to integrate patient-centered skills into the medical
      interview is challenging. Longitudinal training requires significant curricular
      and faculty time. Unsupervised students risk harm if they uncover and
      inappropriately manage psychosocial issues in actual patients. They fear saying
      the wrong thing in emotionally charged situations. Two half-day workshops for pre
      clinical students integrate patient- and physician-centered interviewing. The
      first occurs early in the first year. The second, late in the second year,
      presents interview challenges (e.g., breaking bad news). Ten professional actors
      portray standardized patients (SPs). Groups of 10 to 15 students interview an SP,
      each eliciting a part of the patient's story. Qualitative evaluation revealed
      that, for many students, SPs afford the opportunity to experiment without harming
      real patients. Students view the workshops as effective (mean score for first
      year students, 6.6 [standard deviation (SD), 1.0], second-year students, 7.1 [SD,
      0.7] on a Likert-type scale: 1 = not at all effective to 8 = very effective).

PMID- 12220368
TI  - Effect of health beliefs on delays in care for abnormal cervical cytology in a
      multi-ethnic population.
AB  - CONTEXT: Women from racial and ethnic minorities in the United States have higher
      rates of cervical cancer and present with later stage disease compared to whites.
      Delays in care for abnormal Papanicolaou (Pap) smears can lead to missed cases of
      cervical cancer or late-stage presentation and may be one explanation for these
      differences. OBJECTIVE: To determine if race and ethnicity, health beliefs, and
      cancer knowledge are associated with delays in care for abnormal Pap smears.
      DESIGN, PARTICIPANTS, AND SETTING: We conducted a mailed survey with telephone
      follow-up of all women with an abnormal Pap smear who received care at Kaiser
      Permanente Los Angeles Medical Center between October 1998 and October 1999 (n =
      1,049). MEASUREMENTS AND MAIN RESULTS: A delay in care was defined as not
      attending the first scheduled clinic visit to follow up on an abnormal Pap smear,
      or requiring multiple contact attempts, including a certified letter, to schedule
      a follow-up visit. Our response rate was 70% (n = 733) and the sample was 51%
      Latina. Spanish-speaking Latinas and women of Asian descent were more likely to
      endorse fatalistic beliefs and misconceptions about cancer. Thirteen percent of
      the sample delayed follow-up on their abnormal Pap smear. Women who delayed care
      were more fatalistic and endorsed more misconceptions about cervical cancer.
      Delays in care were not independently associated with race and ethnicity.
      CONCLUSIONS: Health beliefs and cancer knowledge differed by race and ethnicity
      among women in a large managed care organization. Fatalistic health beliefs and
      misconceptions about cancer, but not race and ethnicity, were independently
      associated with delays in care.

PMID- 12220369
TI  - Quantification of the Risk of Corticosteroid-induced Diabetes Mellitus Among the
      Elderly.
AB  - We conducted a population-based cohort study using administrative databases to
      quantify the association between oral and inhaled corticosteroid use and onset of
      diabetes mellitus in the elderly. Proton pump inhibitor (PPI) users were used as
      a control group. Relative to PPI users (N = 53,845), oral corticosteroid users (N
      = 31,864) were more likely to develop diabetes (adjusted rate ratio [aRR], 2.31;
      95% confidence interval [95% CI], 2.11 to 2.54); however, inhaled corticosteroid
      users (N = 38,441) were not (aRR, 1.03; 95% CI, 0.93 to 1.14). The estimated
      number needed to harm for continuous use of oral corticosteroids relative to PPIs
      over 1, 2, and 3 years of use were 41, 23, and 16, respectively.

PMID- 12220371
TI  - Sunlight and vitamin D: both good for cardiovascular health.

PMID- 12220370
TI  - Gambling: an addictive behavior with health and primary care implications.
AB  - Over the past several decades, and particularly during the last 10 to 15 years,
      there has been a rapid increase in the accessibility of legalized gambling in the
      United States and other parts of the world. Few studies have systematically
      explored the relationships between patterns of gambling and health status.
      Existing data support the notion that some gambling behaviors, particularly
      problem and pathological gambling, are associated with nongambling health
      problems. The purpose of this article is to provide a perspective on the
      relationship between gambling behaviors and substance use disorders, review the
      data regarding health associations and screening and treatment options for
      problem and pathological gambling, and suggest a role for generalist physicians
      in assessing problem and pathological gambling. A rationale for conceptualization
      of pathological gambling as an addictive disorder and a model proposing stress as
      a possible mediating factor in the relationship between gambling and health
      status are presented. More research is needed to investigate directly the
      biological and health correlates associated with specific types of gambling
      behaviors and to define the role for generalist physicians in the prevention and
      treatment of problem and pathological gambling.

PMID- 12220372
TI  - Influenza vaccines: why are we missing high-risk patients?

PMID- 12220373
TI  - Practitioners and clinical trials.

PMID- 12220374
TI  - Myotonic dystrophy type 2.
AB  - Myotonic dystrophy type 2 (DM2) is a clinically but not genetically
      heterogeneous, multisystem disorder, that is clinically similar to, but distinct
      from myotonic dystrophy type 1 (DM1). Initially, different phenotypes of DM2 were
      described by Ricker (proximal myotonic myopathy, PROMM), Ranum (myotonic
      dystrophy 2, DM2) and Udd (proximal myotonic dystrophy, PDM). Clinical features
      these three phenotypes had in common were diffuse, proximal or distal weakness,
      wasting, myotonia, cataract, cerebral, endocrine and cardiac abnormalities.
      Initially, the clinical differences between DM1 and PROMM seemed unmistakable,
      but meanwhile it has become apparent that the clinical differences between these
      entities are blurring. In 1999, Day et al., Meola et al. and Ricker et al. mapped
      the mutated gene of all three phenotypes to chromosome 3q. In 2001, the three
      different phenotypes were found to rely on the same mutation in the ZNF9 gene on
      chromosome 3q21.3. Although DM2 may be clinically heterogeneous, it is by result
      of a mutation in a single gene. The mutation responsible for DM2 is a CCTG-repeat
      expansion of 75-11 000 repeats in intron 1 of the ZNF9 gene on chromosome 3q21.3.
      Because of the clinical heterogeneity, the diagnosis of DM2 should rely on DNA
      analysis alone.

PMID- 12220375
TI  - The neural networks of music.
AB  - Recent neuropsychological, transcranial Doppler sonographic, positron emission
      tomographic and functional nuclear magnetic resonance studies have indicated that
      musical perception is not dependent on the right hemisphere but on neural
      networks corresponding to the fundamental components of music in both
      hemispheres. In the brain there is no centre for music. Musicians have cerebral
      characteristics, anatomical as well as functional, which are correlated with the
      age at which they began their musical studies. This argues for cortical
      reorganization as a result of musical training. Whether these characteristics are
      to be ascribed to cortical plasticity alone, or to an innate structural property,
      or to both, remains an open question, however. Investigation of chromosomal
      defects, biochemical abnormalities and morphological features of congenital and
      degenerative brain diseases can provide further insight into the cerebral
      substrate of musicality.

PMID- 12220376
TI  - A French cluster of Creutzfeldt-Jakob disease: a molecular analysis.
AB  - We report the molecular and phenotypic analysis of a French cluster of three
      cases of Creutzfeldt-Jakob disease (CJD), two of them occurring in 1998 in the
      same village and the other in 1995 in a neighboring village. Analyses of the
      occurrence of these events in a close area with less than 3000 inhabitants over
      the 1992-1999 notification period confirmed that they are rare. This could be
      explained either by a common source of contamination or by the coincidental
      occurrence of either sporadic or genetic CJD. We applied genetic analysis and
      brain PrPres typing to explore these CJD cases. The three patients did not carry
      any mutation in their prion protein gene coding sequence. All were homozygous for
      methionine at the polymorphic codon 129. Brain tissue was available from two
      cases that died in 1998. The two patients showed different PrPres profiles on
      Western blot and distinct clinico-pathological features. These findings do not
      support the conclusion that in these three cases, CJD was acquired from a unique
      source of contamination and suggest that concurrent occurrence of sporadic CJD
      accounted for this CJD cluster.

PMID- 12220377
TI  - Visual deficits in a patient with 'kaleidoscopic disintegration of the visual
      world'.
AB  - We describe psychophysical, neuropsychological and neuro-ophthalmological studies
      of visual abilities in a patient who, following a right hemisphere stroke, had
      difficulty in combining parts of objects into a whole and in reading. Strikingly,
      her perceptual problems were accentuated when the objects moved or when she
      moved. Formal testing showed that her main deficits were in depth perception,
      various tasks of motion and object recognition of degraded stimuli. But low-level
      detection and discrimination of form and color were normal. Despite her deficits
      in visual motion and degraded static-object recognition, her visual recognition
      of 'biological motion' stimuli was normal. Structural magnetic resonance imaging
      revealed an infarct in the ventro-medial occipito-temporal region, extending
      ventro-laterally and leading to a 'kaleidoscopic disintegration of visible
      objects'.

PMID- 12220378
TI  - Molecular genetic analysis of the alpha-synuclein and the parkin gene in
      Parkinson's disease in Finland.
AB  - Two mutations in the alpha-synuclein gene and various mutations in the parkin
      gene are associated with familial Parkinson's disease (PD). The present study was
      performed to analyse if mutations in these genes could be detected in Finnish
      patients with familial PD. The subjects comprised 22 unrelated patients with
      familial PD. The molecular genetic analysis consisted of sequence analysis of the
      non-coding and coding exons of the alpha-synuclein gene and screening of eight
      point mutations in the parkin gene. In addition, a total of 67 controls and 45
      patients with sporadic PD were included in the association analysis on
      polymorphism of the alpha-synuclein gene. Screened point mutations in the parkin
      gene were not detected. Sequencing of the coding exons 2-6 of the alpha-synuclein
      gene did not reveal any mutations or polymorphisms. However, three novel
      alterations in the T10A7 sequence at the 5' end of the non-coding exon 1' of the
      alpha-synuclein gene were found. The frequencies of the exon 1' polymorphic
      genotypes or alleles between familial PD patients and control subjects revealed
      no statistically significant differences. No association for sporadic PD was
      observed. The results do not support a role for the alpha-synuclein gene or point
      mutations of the parkin gene in familial PD in our sample.

PMID- 12220379
TI  - Polymorphisms in the tau gene in sporadic frontotemporal dementia and other
      neurodegenerative disorders.
AB  - The tau gene on chromosome 17 is fundamental in the pathogenesis of a number of
      neurodegenerative disorders. Mutations in tau are found in familial
      frontotemporal dementia (FTD) and the A0/A0 genotype associated with progressive
      supranuclear palsy (PSP). This study investigates the hypothesis that
      polymorphisms in the tau gene are associated with sporadic FTD. Western
      Australian populations of patients with sporadic frontotemporal dementia, PSP,
      Alzheimer's disease (AD), Huntington's disease (HD) and normal controls were
      studied. A new method was developed using fluorescently labelled probes to
      determine polymorphisms in the GT repeat region of intron 9. The A0/A0 genotype
      was found in 95% of PSP patients (n=20), 58.3% of FTD patients (n=48), 60.8% of
      AD patients (n=52), 75% of HD patients (n=40), and 75% of normal controls (n=40).
      None of these differences in genotype frequency were found to be significant by
      the Fisher exact test (P > 0.05). There were no significant differences in the
      frequencies of A0/A3 and A0/A1 haplotypes. We have not observed a significant
      increase in the A0/A0 genotype frequency in sporadic frontotemporal dementia
      suggesting that this polymorphism is unlikely to be related to the development of
      this condition. Furthermore, we have observed an increase in the A0/A0 genotype
      in PSP which did not reach statistical significance, suggesting that there may be
      population differences in the role of genetic factors in conferring risks to
      neurodegenerative disorders. Our work does not exclude that tau may interact with
      other genetic factors.

PMID- 12220380
TI  - Depressive symptoms and MRI changes in multiple sclerosis.
AB  - To determine whether changes in specific regions of the brain can contribute to
      the development of depression in patients with multiple sclerosis (MS). We
      prospectively studied 90 patients with clinically definite MS. Disability,
      independence, cognitive performances, and depressive and anxiety symptoms have
      been assessed at baseline and 2 years later. At these two time-points, patients
      underwent a 1.5-T magnetic resonance examination of the brain including T1- and
      T2-weighted images. Calculation of regional and total lesion loads (LL) have been
      performed by a semiautomatic technique; total and regional brain volumes have
      been calculated by a fully automatic highly reproducible computerized interactive
      program. Measurements of LL did not show any significant difference between
      depressed and non-depressed patients. Brain atrophy was significantly more
      conspicuous in the left frontal lobe (P=0.039), in both frontal lobes (P=0.046)
      and showed a trend towards a difference in the right frontal lobe (P=0.056), in
      the right temporal lobe (P=0.057) and in both temporal lobes (P=0.072) of
      depressed patients. Disability, independence and cognitive performances were
      similar in depressed and non-depressed patients (P=NS). Spearman correlation
      analysis and multiple-regression analysis demonstrated that the severity of the
      depressive symptoms score was associated both with the disability score and the
      right temporal brain volume. Destructive lesions in the right temporal lobe can
      contribute to the severity of depression in patients with MS but the influence of
      the severity of neurological impairment should be taken into account.

PMID- 12220381
TI  - Health-related quality of life and its relationship to cognitive and emotional
      functioning in multiple sclerosis patients.
AB  - The existing knowledge about the health-related quality of life (HRQoL) and its
      relationship to cognitive and/or emotional functioning in multiple sclerosis (MS)
      is scarce. We assessed differences between subgroups of MS outpatients (n = 209)
      on one HRQoL instrument: a version of the Functional Assessment of Multiple
      Sclerosis quality of life instrument; on two cognitive functioning tests: the
      Mini-Mental State Examination and the clock drawing test; and on two emotional
      functioning tests: the Hamilton Rating Scale for Depression and the Hamilton
      Rating Scale for Anxiety. Three disease-related characteristics were assessed:
      physical disability, duration of the illness, and clinical course. The results
      showed that each of these has an effect on at least one dimension of HRQoL and on
      one mental functioning test. Thus, the more severe, the more progressive, and the
      longer the illness duration, the lower the HRQoL. Likewise, cognitive mean scores
      decreased and emotional mean scores increased with greater illness severity and
      progressive the MS. Furthermore, we also found significant correlations between
      cognitive and emotional functioning tests and HRQoL dimensions. Thus, the worse
      cognitive functioning and the higher depressive and anxiety symptoms score the
      lower the HRQoL.

PMID- 12220383
TI  - Subarachnoid haemorrhage occurrence exhibits a temporal pattern - evidence from
      meta-analysis.
AB  - The aim of the present meta-analysis was to determine a temporal pattern of
      occurrence of subarachnoid haemorrhage (SAH). A MEDLINE 1966-2001 and EMBASE
      (1980-2001) literature search and hand search of relevant references were
      performed for population-based incidence studies that reported the time of SAH
      occurrence. Data from all identified relevant studies were combined into a pooled
      rate ratio (RR), with corresponding 95% confidence intervals (CI) using the
      Mantel-Haenszel method. Overall, eight population-based studies were included in
      the analysis. A total of 2533 first-ever cases of SAH were reported in the
      studies identified. Risk of SAH occurrence was the highest in the period between
      6 am and 12 am (RR = 3.19; 95% CI 3.03-3.36; early morning as a reference
      variable) and between 12 p.m. and 6 p.m. (RR = 2.63; 95% CI 2.47-2.80), in winter
      and spring (RR = 1.10; 95% CI: 1.02-1.17; and RR = 1.07; 95% CI: 1.01-1.13,
      respectively; summer as a reference variable) and on Sunday (RR = 1.22; 95% CI
      1.09-1.37; Monday as a reference variable). The evidence suggests that occurrence
      of SAH exhibits a seasonal (winter and spring) peak, diurnal (late morning peak)
      and daily (Sunday peak) pattern. It is suggested that the occurrence of some
      major acute vascular events (total ischaemic strokes, intracerebral haemorrhage
      and myocardial infarction) may be influenced by common triggering factors.

PMID- 12220382
TI  - Upregulated survivin expression in activated T lymphocytes correlates with
      disease activity in multiple sclerosis.
AB  - Programmed cell death (apoptosis) is critical for the normal development and
      homeostasis of the immune system. There is emerging evidence that failure of
      apoptosis to eliminate potentially pathogenic, autoreactive T lymphocytes may be
      involved in the pathogenesis of multiple sclerosis (MS). This failure is related
      to multiple abnormalities of apoptosis-regulatory molecules that involve
      survivin, a recently described cell cycle-regulated anti-apoptosis protein. In
      this study, we investigated the relationship between survivin expression in
      peripheral T lymphocytes and clinical features of MS. We detected a significant
      over-expression of survivin in mitogen stimulated T lymphocytes from patients
      with active MS when compared with corresponding expression in patients with
      stable MS or those with inflammatory and non-inflammatory neurologic disorders.
      This over-expression of survivin in patients with active MS correlated with
      cellular resistance to apoptosis and with features of disease activity, such as
      disease duration and the number of enhanced lesions on cranial magnetic resonance
      imaging. There was no correlation between cellular survivin levels and the
      expression of other apoptosis-inhibitory proteins, such as Bcl-2 and Fas
      associated death domain-like interleukin-1beta-converting enzyme inhibitory
      protein (FLIP). Our findings indicate that cellular over-expression of the novel
      anti-apoptosis protein survivin is a feature of clinically active MS.

PMID- 12220384
TI  - Paroxysmal kinesigenic choreoathetosis because of cryptogenic myelitis. Remission
      with carbamazepine and the pathogenetic role of altered sodium channels.
AB  - Lesions of the spinal cord causing paroxysmal kinesigenic choreoathetosis are
      rare and most of the reported cases have been because of multiple sclerosis. We
      now describe this movement disorder occurring in a patient who developed a
      myelitis of unknown aetiology. A typically striking remission followed treatment
      with carbamazepine. It is suggested that the effect of the drug and the disorder
      itself may both be explained on the basis of altered sodium channels.

PMID- 12220385
TI  - Natural killer cell proliferation and circulating cytokines in patients with
      bilateral basal ganglia calcification.
AB  - Ten adult patients with symmetrical calcifications in the bilateral basal ganglia
      (diagnosed as physiological calcifications) were analyzed for lymphocyte subsets
      and cytokines. Increased number of natural killer (NK) cells were identified in
      the peripheral blood of seven patients by lymphocyte subset analysis. Tumor
      necrosis factor-alpha was detected in the sera of five patients and interferon
      gamma was detected in one patient. In summary, NK cell propagation and
      circulating cytokines, particularly tumor necrosis factor-alpha, may be involved
      in the etiology of basal ganglia calcification.

PMID- 12220386
TI  - The co-occurrence of headache and musculoskeletal symptoms amongst 51 050 adults
      in Norway.
AB  - We have evaluated the association between headache and musculoskeletal symptoms
      in a large cross-sectional population-based study. Between 1995 and 1997, all 92
      566 adults in Nord-Trondelag County in Norway were invited to participate in a
      health survey. A total of 51 050 (55%) responded to questions concerning headache
      and musculoskeletal symptoms. Both migraine and non-migrainous headache were
      strongly associated with musculoskeletal symptoms. However, frequency of headache
      had a higher impact than headache diagnosis on this association. Thus, the
      prevalence of chronic headache (headache >14 days/month) was more than four times
      higher (OR = 4.6; 95% CI 4.0-5.3) in the group of individuals with
      musculoskeletal symptoms than in those without. Individuals with neck pain were
      more likely to suffer from headache as compared with those with musculoskeletal
      symptoms in other restricted areas. In conclusion, there was a strong association
      between chronic headache and musculoskeletal symptoms, which may have
      implications for the choice of treatment.

PMID- 12220387
TI  - The trend in public attitudes in the Czech Republic towards persons with
      epilepsy.
AB  - This study evaluates trends in public familiarity with and attitudes towards
      people with epilepsy over a 16-year time-period. A survey exploring the Czech
      public's attitudes towards and knowledge of epilepsy used a modified version of a
      questionnaire first used in the USA in 1949, and in the Federal Republic of
      Germany beginning in 1968. This survey was carried out for the first time in the
      Czech Republic (then Czechoslovakia) in 1981, and then again in 1984. There was
      no significant difference between the 1981 and 1984 responses. A slightly
      modified questionnaire was used in 1997-1998, with evaluable responses gathered
      from 235 people. In comparison with the 1981 study, people's acquaintance with
      epilepsy was significantly higher in 1997-1998. In 1997-1998, about 94% of the
      people surveyed had some information about epilepsy (78% in 1981). Intolerance
      towards children with epilepsy dropped from 29 to 13%. About 30% of the people
      surveyed considered epilepsy to be a mental disease (50% in 1981). Employment of
      people with epilepsy was recommended by 74% (42% in 1981). In contrast with the
      situation about 16 years earlier, there were fewer important differences from the
      results of similar surveys taken in other European countries. However, the
      answers concerning the willingness to help a person having a seizure show that,
      despite certain progress, the quality of information that the Czech population
      has is not fully satisfactory.

PMID- 12220388
TI  - Hypertensive encephalopathy: persistent MR-abnormalities in a patient with good
      clinical recovery.

PMID- 12220389
TI  - SSPE - a forgotten disease?

PMID- 12220390
TI  - Severe axonal polyradiculoneuritis and brainstem encephalitis due to Mycoplasma
      pneumoniae infection.

PMID- 12220392
TI  - Broad therapeutic benefits in patients with probable vascular dementia or
      Alzheimer's disease with cerebrovascular disease after treatment with
      galantamine.

PMID- 12220391
TI  - Cerebellar ataxia after repeated hypoglycemia.

PMID- 12220405
TI  - Plasmid promiscuity: meeting the challenge of DNA immigration control.

PMID- 12220406
TI  - Compatible solutes of organisms that live in hot saline environments.
AB  - The accumulation of organic solutes is a prerequisite for osmotic adjustment of
      all microorganisms. Thermophilic and hyperthermophilic organisms generally
      accumulate very unusual compatible solutes namely, di-myo-inositol-phosphate, di
      mannosyl-di-myo-inositol-phosphate, di-glycerol-phosphate, mannosylglycerate and
      mannosylglyceramide, which have not been identified in bacteria or archaea that
      grow at low and moderate temperatures. There is also a growing awareness that
      some of these compatible solutes may have a role in the protection of cell
      components against thermal denaturation. Mannosylglycerate and di-glycerol
      phosphate have been shown to protect enzymes and proteins from thermal
      denaturation in vitro as well, or better, than compatible solutes from
      mesophiles. The pathways leading to the synthesis of some of these compatible
      solutes from thermophiles and hyperthermophiles have been elucidated. However,
      large numbers of questions remain unanswered. Fundamental and applied interest in
      compatible -solutes and osmotic adjustment in these organisms, drives research
      that, will, in the near future, allow us to understand the role of compatible
      solutes in osmotic protection and thermoprotection of some of the most
      fascinating organisms known on Earth.

PMID- 12220407
TI  - Multiple influences of nitrate on uranium solubility during bioremediation of
      uranium-contaminated subsurface sediments.
AB  - Microbiological reduction of soluble U(VI) to insoluble U(IV) has been proposed
      as a remediation strategy for uranium-contaminated groundwater. Nitrate is a
      common co-contaminant with uranium. Nitrate inhibited U(VI) reduction in acetate
      amended aquifer sediments collected from a uranium-contaminated site in New
      Mexico. Once nitrate was depleted, both U(VI) and Fe(III) were reduced
      concurrently. When nitrate was added to sediments in which U(VI) had been
      reduced, U(VI) reappeared in solution. Parallel studies with the dissimilatory
      Fe(III)-, U(VI)- and nitrate-reducing microorganism, Geobacter metallireducens,
      demonstrated that nitrate inhibited reduction of Fe(III) and U(VI) in cell
      suspensions of cells that had been grown with nitrate as the electron acceptor,
      but not in Fe(III)-grown cells. Suspensions of nitrate-grown G. metallireducens
      oxidized Fe(II) and U(IV) with nitrate as the electron acceptor. U(IV) oxidation
      was accelerated when Fe(II) was also added, presumably due to the Fe(III) being
      formed abiotically oxidizing U(IV). These studies demonstrate that although the
      presence of nitrate is not likely to be an impediment to the bioremediation of
      uranium contamination with microbial U(VI) reduction, it is necessary to reduce
      nitrate before U(VI) can be reduced. These results also suggest that anaerobic
      oxidation of U(IV) to U(VI) with nitrate serving as the electron acceptor may
      provide a novel strategy for solubilizing and extracting microbial U(IV)
      precipitates from the subsurface.

PMID- 12220408
TI  - Analysis of sMMO-containing type I methanotrophs in Lake Washington sediment.
AB  - Methane-oxidizing bacteria (methanotrophs) containing soluble methane
      monooxygenase (sMMO) are of interest in natural environments due to the high co
      metabolic activity of this enzyme with contaminants such as trichloroethylene. We
      have analysed sMMO-containing methanotrophs in sediment from a freshwater lake.
      Environmental clone banks for a gene encoding a diagnostic sMMO subunit (mmoX)
      were generated using DNA extracted from Lake Washington sediment and subjected to
      RFLP analysis. Representatives from the six RFLP groups were cloned and
      sequenced, and all were found to group with Type I Methylomonas mmoX, although a
      majority were divergent from known Methylomonas mmoX sequences. Direct
      hybridization of Lake Washington sediment DNA was carried out using a series of
      sMMO- and Methylomonas-specific probes to assess the significance of these sMMO
      containing Methylomonas-like strains in the sediment. The total sMMO-containing
      population and the sMMO-containing Methylomonas-like population were estimated to
      be similar to previous estimates for total methanotrophs and Type I
      methanotrophs. These results suggest that the major methanotrophic population in
      Lake Washington sediment consists of sMMO-containing Methylomonas-like (Type I)
      methanotrophs. The whole-cell TCE degradation kinetics of such a strain, LW15,
      isolated from this environment, were determined and found to be similar to values
      reported for other sMMO-containing methanotrophs. The numerical significance of
      sMMO-containing Methylomonas-like methanotrophs in a mesotrophic lake environment
      suggests that these methanotrophs may play an important role in methanotroph
      mediated transformations, including co-metabolism of halogenated solvents, in
      natural environments.

PMID- 12220409
TI  - Is bioconvection enhancing bacterial growth in quiescent environments?
AB  - Bioconvection is an intriguing pattern-forming phenomenon driven by the swimming
      activity of various aquatic microorganisms. It is generally assumed that
      bioconvection has a positive effect on the entire microbial population by
      carrying oxygen into deep layers of non-aerated suspensions. In order to examine
      the presence of such a biological benefit, we analysed the correlation between
      bioconvective pattern formation and population growth of several Bacillus
      subtilis and Bacillus licheniformis strains under non-aerated conditions.
      Bioconvection is a robust phenomenon, we observed its development in numerous
      cultures of various strains and growth phases. Nevertheless, evaluation of the
      data has not revealed detectable positive effects on population growth,
      questioning the potential biological relevance of bioconvection in natural
      habitats.

PMID- 12220410
TI  - Metabolic biomarkers for monitoring anaerobic naphthalene biodegradation in situ.
AB  - During the anaerobic biodegradation of naphthalene and methylnaphthalene, unique
      metabolites are formed by specific microbial carboxylation and ring-reduction
      reactions. Groundwater samples from an anoxic, shallow aquifer contaminated with
      gasoline were examined for the presence of these metabolites by extraction,
      derivatization and gas chromatography coupled to mass spectroscopy. Several
      metabolites [2-naphthoic acid (2-NA), tetrahydro-2-naphthoic acid (TH-2-NA),
      hexahydro-2-naphthoic acid (HH-2-NA) and methylnaphthoic acid (MNA)] were found
      to be present in the groundwater samples. The concentration of 2-NA at each
      monitoring well was quantified and correlated to the zones of contamination. The
      presence of the other metabolites in the same wells as 2-NA was used as
      confirmation that the anaerobic pathway was indeed active. The distribution of
      metabolites at this site shows that they can be used as biomarkers for
      demonstrating in situ biodegradation.

PMID- 12220411
TI  - Mitigation of avian reproductive tract function by Salmonella enteritidis
      producing high-molecular-mass lipopolysaccharide.
AB  - Hens were infected with a wild-type Salmonella enteritidis and its wzz mutant,
      which lacked the ability to make high-molecular-mass lipopolysaccharide (LPS), in
      six experiments paired by dosage and route of exposure. Involution of the
      reproductive tract occurred in 86% of hens that were injected subcutaneously with
      108 cfu of the wild-type strain, but none did so when injected with the wzz
      mutant. In spite of the lack of a specific effect on the reproductive tract,
      infection of hens with the mutant produced more contaminated eggs and
      heterophilic granulomas in developing ova (yolks) than wild type; thus, overall,
      the mutant appeared to be more virulent except after intravenous injection. The
      mutant also decreased shell quality more often than wild type, regardless of
      dosage or route of infection. These results suggest that egg-contaminating
      Salmonella enteritidis that produces high-molecular-mass LPS mitigates signs of
      illness in poultry by altering the response of the avian reproductive tract to
      infection, but without altering the incidence of egg contamination following
      bacteraemia. Further research is warranted to determine whether analyses of shell
      quality might aid in identification of flocks at risk of producing contaminated
      eggs.

PMID- 12220412
TI  - Extremely productive microbial communities in shallow saline pools respond
      immediately to changing meteorological conditions.
AB  - Diel changes in bacterial and cyanobacterial numbers, as well as heterotrophic
      bacterial production, were examined in two shallow alkaline pools, harbouring
      dense populations of cyanobacteria (up to 1100 x 109 cells l-1) and bacteria (up
      to 500 x 109 cells l-1). Together with the recorded bacterial production rates
      (925 micro gC l-1x h-1), these values are the highest reported for natural
      aquatic ecosystems. The investigations were performed during a fair-weather
      situation, and during a rapid change after a long-term fair-weather situation to
      thunderstorms and heavy rainfall. During fair weather, bacterial growth was
      significantly correlated to the diurnal light and temperature cycle. Prokaryotic
      abundances were fairly constant, and loss by grazing and viral lysis must have
      been of significant importance. During the invasion of rainy weather, the
      prokaryotic community showed a strong and immediate response. A significant
      enhancement of bacterial growth followed after rainfall, suggesting that the high
      salt concentrations had inhibited bacterial activity. Changes in bacterial and
      cyanobacterial numbers were consistent with this pattern. From comparison with
      the available literature, we conclude that diel changes of bacterioplankton are
      regulated by a complex combination of environmental factors specific for each
      investigated ecosystem. In the soda pools investigated, external abiotic factors
      were dominant on a diel scale. In larger ecosystems, such factors are much more
      buffered and internal biotic interactions may prevail.

PMID- 12220414
TI  - Fundus rotation gastroplasty: rationale, technique and results.
AB  - Anastomotic leakage is the main factor (up to 30%) for postoperative morbidity
      and mortality after esophageal resection. Compromised anastomotic perfusion after
      dissection of supplying vessels for gastric tube formation and tension on the
      suture line are the two main reasons for anastomotic insufficiency. To prevent
      anastomotic leakage, a new technique for gastric tube formation after esophageal
      resection has been developed and introduced into surgical practice: the fundus
      rotation gastroplasty (FRG). The following paper summarizes rationale, technique
      and early results of this new technique. It is shown that the FRG is a safe and
      effective technique for esophageal reconstruction and offers important advantages
      over conventional gastroplasties: (i). the improved perfusion of the oral part of
      the tube; (ii). the gain of tube length allowing for a safer performance of even
      pharyngeal anastomosis as shown by the low insufficiency rate of 9%; and (iii).
      the increase of remaining gastric reservoir supporting physiologic stomach and
      gut function. Therefore, the FRG seems to be an alternative and safe method for
      esophageal reconstruction, especially for high anastomotic locations.

PMID- 12220415
TI  - Epidemiology of Barrett's esophagus and adenocarcinoma.

PMID- 12220416
TI  - Surgical therapy for Barrett's esophagus: prevention, protection and excision.

PMID- 12220417
TI  - Neoadjuvant treatment of early stage squamous cell carcinoma of the esophagus.

PMID- 12220418
TI  - Neoadjuvant treatment of advanced stage esophageal adenocarcinoma increases
      survival.
AB  - Sophisticated surgical approaches have a definite but limited role in esophageal
      cancer. The majority have systemic disease at presentation, minimal residual
      disease following resection or co-morbid conditions that preclude extensive
      surgery. This paper examines whether neoadjuvant therapy is effective in advanced
      stage disease. A randomized trial, closing September 1995, was followed up to
      determine results at 5 years. All patients were followed up for more than 5
      years. Median survival, based on intention-to-treat, was 17 months for multimodal
      therapy vs. 12 months for surgery alone (P=0.002). Survival based on treatment
      received was 27 months vs. 14 months (P=0.0006). Multimodal therapy enhances
      survival for patients with minimal residual disease. This is consistent with the
      literature. Under-powered trials cannot prove a real difference to be
      significant. Future trials should target patients with minimal residual disease.

PMID- 12220419
TI  - Short esophagus: literature incidence.
AB  - There are controversies regarding existence and incidence of short esophagus. The
      authors reviewed the literature incidence of short esophagus among operated
      patients due to gastroesophageal reflux disease in the last 3 years. The overall
      incidence of short esophagus was 1.53%. The proposed risk factors (paraesophageal
      hernia, Barrett's esophagus, reoperation, esophageal strictures and access route)
      do have a higher incidence of short esophagus, with the exception of the
      Barrett's esophagus. Although several biases can be associated with the review,
      the authors identified the short esophagus incidence in the literature.

PMID- 12220420
TI  - Endoluminal methods of treating gastroesophageal reflux disease.
AB  - Several endoluminal methods of treating gastroesophageal reflux disease (GERD)
      have either been approved, or are under investigation and development. This
      review outlines the two approved methods (Bard's endoluminal sewing machine and
      Curon's Stretta radiofrequency treatment), and describes the available data on
      new methods under investigation. The various methods can be divided into three
      broad categories: methods that create a controlled stricture, methods that bulk
      the gastroesophageal junction, and methods that attempt to create a
      fundoplication. The pros and cons of each method are discussed. Unlike medical
      treatment, these methods attack the reflux itself, not just the symptoms. This is
      a promising approach. However, the controlled stricture and bulking methods do
      not approach the success rate of a standard fundoplication.

PMID- 12220421
TI  - Photodynamic therapy for Barrett's esophagus: a review.
AB  - Barrett's esophagus is the major risk factor for the development of esophageal
      adenocarcinoma, which is increasing in incidence faster than any other cancer in
      the Western world. Barrett's esophagus has previously been considered an
      irreversible lesion that required life-long surveillance to detect malignant
      transformation. However, endoscopic ablative techniques to destroy the abnormal
      mucosa and allow squamous regeneration have now been developed. Photodynamic
      therapy (PDT) is a non-thermal technique where the interaction of a
      photosensitizer in the tissues and light of a known wavelength results in tissue
      destruction. It appears to be an effective tool for ablating dysplasia and
      superficial cancers in Barrett's esophagus. The status of PDT for this disease is
      reviewed.

PMID- 12220422
TI  - Clinicopathological features of early esophageal squamous cell carcinoma with
      subsequent recurrence.
AB  - It has been well known that there is occasionally a postoperative recurrence in
      early esophageal carcinoma. However, the clinicopathologic characteristics of
      early squamous cell carcinoma of the esophagus with a postoperative recurrence
      have not been elucidated. The subjects were 103 patients with early carcinoma of
      the esophagus including 10 patients with subsequent recurrence, who had been
      surgically treated. Clinicopathologic features were compared between patients
      with the presence and absence of recurrence of carcinoma. No special
      clinicopathologic feature was observed in early esophageal carcinomas with
      subsequent recurrence, when compared with early carcinomas without recurrence.
      Physicians should realize that there is always a possibility of recurrence in
      early carcinomas of the esophagus, and that a leading clinical strategy for
      superficial carcinoma of the esophagus is the surgical treatment.

PMID- 12220423
TI  - Cell cycle-regulated factors in esophageal cancer.
AB  - Alterations of cell cycle-regulated genes play an important role in the process
      of carcinogenesis, and some of them are thought to be prognostic factors in
      esophageal cancer. The expressions of p53, p16, pRB and Cyclin D1 proteins were
      evaluated immunohistochemically in 144 patients who underwent curative
      esophagectomy without any adjuvant therapy before surgery. p53 overexpression was
      observed in 99 (69%) out of the 144 patients. No significant correlation was
      noted between p53 and any other gene expression. p16 expression was observed in
      12 (8.3%) out of all cases. A negative correlation was recognized between p16 and
      Cyclin D1 expression (P=0.0004). pRB expression was observed in 130 (90.3%) out
      of all cases, whereas pRB expression was not observed in 11 out of the 12
      patients with p16-positive tumors. A negative correlation was also found between
      p16 and pRB (P < 0.0001). A positive correlation was noted between pRB and Cyclin
      D1 expression (P=0.0009). The cumulative survival rate of patients without pRB
      expression was significantly lower than that of patients with positive expression
      (P=0.003). In the multivariate survival analysis, pRB expression was an
      independent prognostic factor. In 98% of all patients with esophageal cancer,
      impairment of the G1 checkpoint is due to a loss of function by p16, pRB or
      Cyclin D1, which showed a negative correlation in each factor. In addition,
      aberrant expression of pRB is useful as a prognostic factor in esophageal cancer.

PMID- 12220424
TI  - Multivariate analysis of clinical, operative and pathologic features of
      esophageal cancer: who needs adjuvant therapy?
AB  - The failure of adjuvant therapy to significantly improve the prognosis of
      patients undergoing esophago-gastrectomy for cancer may be because of poor
      patient selection. We sought prognostic factors that would identify those
      patients who could benefit from adjuvant therapy. Data on 15 possible prognostic
      factors were prospectively collected on 225 patients undergoing esophago
      gastrectomy at a single institution, and univariate and multivariate analyzes
      performed. T, N, M and overall UICC stage, differentiation, involvement of the
      circumferential resection margin and number of metastatic of lymph nodes were
      identified as significant prognostic factors by univariate analysis. Multivariate
      analysis revealed that the completeness of resection (R-category), ratio of
      metastatic to total nodes resected and the presence of vascular invasion were
      independently significant prognostic factors. Following R0 or R1 resection,
      patients with a metastatic to total lymph node ratio > 0.2 and /or the presence
      of vascular invasion have a poor prognosis, and the effects of adjuvant therapy
      in these patients should be studied.

PMID- 12220425
TI  - Efficacy of mediastinal lymphadenectomy in transhiatal esophagectomy with and
      without diaphragm opening: a cadaveric study.
AB  - Transhiatal esophagectomy (THE) is believed to induce a lower morbidity and
      mortality compared with transthoracic esophagectomy, but to be inefficient in
      performing mediastinal lymphadenectomy. Some surgeons are convinced that
      lymphadenectomy of the lower mediastinum in THE and transthoracic esophagectomy
      are equivalent. To test this, the authors performed THE in 20 cadavers (10 with
      and 10 without diaphragm opening). The number of lymph nodes resected with the
      esophagus and dissected through the hiatus was counted. After THE, the thorax was
      opened and the number of residual lymph nodes was evaluated. Complications were
      also assessed. The results show that lymphadenectomy in THE is incomplete in the
      lower mediastinum and not possible in the upper mediastinum; comparing THE with
      and without diaphragm opening, the first permits resection of a superior number
      of lymph nodes with the esophagus and dissection of a higher number of nodes
      through the hiatus. It is concluded that THE does not provide an effective
      mediastinal lymphadenectomy.

PMID- 12220426
TI  - Laparoscopic fundoplication in mentally normal children with gastroesophageal
      reflux disease.
AB  - Laparoscopic antireflux surgery has been performed in neurologically impaired and
      scoliotic children. We aimed to assess the effectiveness of laparoscopic
      fundoplication in mentally normal children with gastroesophageal reflux disease
      that failed to respond to medical therapy. Data were prospectively collected
      (symptoms, medical therapy, endoscopies' findings) on 12 children (nine boys,
      three girls) aged 9-15 years with gastroesophageal reflux disease. Pre- and
      postoperative ambulatory 24-h pH and DeMeester and Johnson scores were also
      recorded. Effectiveness of surgery was assessed by comparison of pre- and
      postoperative total acid exposure time, Visick grade, need for antireflux
      medication and symptom scores. In total, 11 children underwent a laparoscopic
      Nissen fundoplication and one underwent a Toupet procedure. Median length of stay
      was 2 (2-3) nights. The median preoperative pH acid exposure time (AET) was 4.7
      (0.8-16.4) percent compared with postoperative AET of 0.4 (0-3) percent. Early
      postoperative dysphagia occurred in four out of 12 patients, requiring a total of
      six dilatations. Postoperative Visick scores were: grade I=7 and grade II=5.
      Laparoscopic fundoplication can be safely performed and is effective in children
      with GERD who have failed to respond to medical therapy.

PMID- 12220427
TI  - Efficacy of Rigiflex balloon dilatation in 12 children with achalasia: a 6-month
      prospective study showing weight gain and symptomatic improvement.
AB  - Achalasia cardia is a disease of adolescents and is rare in children. In total,
      12 children with primary achalasia, with a mean age of 10.8 +/- 2 years, were
      prospectively evaluated for the efficacy of a 30-mm-diameter Rigiflex balloon for
      relief of symptoms and weight gain after 1 and 6 months of follow up. The 12
      children were evaluated and treated for achalasia, with pneumatic balloon
      dilatation, from January 1998 to December 2000. They were studied for basal, 1-,
      and 6-month post-dilatation composite symptoms for dysphagia, regurgitation,
      night cough and heartburn. Basal and 5-min post-dilatation barium swallow were
      obtained to compare barium height and width for efficacy of dilatation and to
      evaluate for complications. There were no complications. Barium height, width,
      composite symptom score and weight improved significantly up to the 6-month
      follow up. Rigiflex balloon dilatation of 30-mm diameter is safe and effective in
      children with achalasia.

PMID- 12220429
TI  - Endoscopic treatment of a Zenker's diverticulum using argon plasma coagulation in
      a patient with massive cachexia and esophageal obstruction: a case report and
      review of literature.
AB  - A case report is presented of an 86-year-old man in a very poor general condition
      with a 10-year history of a Zenker's diverticulum as a cause of a complete
      obstruction of the esophagus with subsequent aphagia and massive cachexia.
      Because of high surgical risk and contraindications to general anesthesia, an
      approach with the flexible endoscope to perform cricopharyngeal myotomy was
      undertaken. Several attempts with the flexible endoscope by experienced
      investigators had been performed until the esophageal inlet was intubated and
      argon plasma coagulation could be applied in several sessions to divide the
      tissue bridge between the esophagus and the Zenker diverticulum to successfully
      restore the pharyngoesophageal passage.

PMID- 12220428
TI  - Long-term effects of myotomy and partial fundoplication for esophageal achalasia.
AB  - Controversy persists in the surgical approach to treat esophageal achalasia. This
      investigation reports the long-term effects of esophageal myotomy and partial
      fundoplication in treating this disorder. From 1984 to 1998, 32 patients with
      achalasia underwent myotomy and partial fundoplication (Belsey Mark IV) using a
      left thoracotomy. The median follow up is 7.2 years. Assessments include clinical
      evaluation, esophagogram, radionuclide transit, manometry, 24-h pH, and
      endoscopy. There is no complication and no mortality. Preoperative assessment was
      compared with that in 0-3, 3-7, and 7-16 postoperative years. Clinically, the
      prevalence of dysphagia was decreased from 100% to 6%, 12%, and 13%, respectively
      (P < 0.001). Heartburn remains unchanged (P > 0.25). On radiology, the prevalence
      of barium stasis was decreased from 97% to 44%, 48%, and 47%, respectively
      (P=0.001), whereas a pseudo-diverticulum was observed in two-thirds of patients
      after operation (P=0.001). Percent radionuclide stasis at 2 min was measured as
      70%, 17%, 20%, and 20%, respectively (P=0.001). Manometrically, lower esophageal
      sphincter (LES) gradient was decreased from 29 to 10, 9, and 9 mmHg, respectively
      (P=0.001). LES relaxation was improved from 41% preoperatively to 100%
      postoperatively at each postoperative period (P < 0.001). An abnormal acid
      exposure was observed in four patients after the operation. Endoscopy documented
      mucosal damage in three patients (P > 0.25). In conclusion, on long-term follow
      up, myotomy and partial fundoplication for achalasia relieve obstructive symptoms
      and improve esophageal emptying, and reduce LES gradient and improve LES
      relaxation. Acid reflux is recorded in 13% of patients and esophageal mucosal
      damage is identified in 11% of the patient population. A longer myotomy not
      covered by the fundoplication results in pseudodiverticulum formation and
      increased esophageal retention.

PMID- 12220430
TI  - Diaphragmatic herniation after transhiatal esophagectomy.
AB  - Increasing experience with transhiatal esophagectomy (THE) has brought with it a
      good understanding of the advantages and disadvantages of the technique. As in
      our case, diaphragmatic hernias after THE may result from excess manipulation and
      extension of the hiatus during surgery. The varying nature of the clinical
      presentation may cause delay in diagnosis. We report our case and discuss how to
      diagnose and manage this complication under the sum of cases reported previously
      in English literature.

PMID- 12220431
TI  - Sliding hernia simulating esophageal tumor on computed tomography.
AB  - Diaphragmatic hernias are the most common abnormalities of gastrointestinal
      system especially in elderly patients. The radiographic findings of diaphragmatic
      hernias on esophagram are well known, but when incidentally found in an
      asymptomatic patient on axial computed tomography (CT) sections, the appearance
      of diaphragmatic hernia may mimic many other conditions. Our purpose is to
      present the CT findings of sliding hernia in an incidentally found asymptomatic
      patient, and to differentiate it from the other abnormalities that can be located
      in the distal paraesophageal area with the same appearance characteristics.

PMID- 12220433
TI  - Novel neuropeptide Y1 and Y5 receptor gene variants: associations with serum
      triglyceride and high-density lipoprotein cholesterol levels.
AB  - Neuropeptide Y (NPY) appears to play a critical role in the integration of
      appetite and energy expenditure through NPY Y1 and Y5 receptor subtypes.
      Moreover, the NPY Y1 receptor is highly expressed on human adipocytes, where it
      inhibits lipolysis. The genes encoding these receptors are transcribed co
      ordinately in opposite directions from a common promoter in a region of
      chromosome 4 that has been previously linked to triglyceride and small low
      density lipoprotein (LDL) particle concentration. Therefore, the purpose of this
      investigation was to examine the relationship between polymorphisms in the genes
      encoding NPY Y1 and Y5 and the development of obesity and dyslipidemia. We
      screened the promoter and coding regions and identified four polymorphic
      variants. One of these, a cytosine to thymine (C-->T) substitution in the
      untranslated region between the genes for NPY Y1 and Y5 (allele frequency 0.11),
      was significantly associated with both lower fasting triglyceride level (152 vs
      125 mg/dl), and higher high-density lipoprotein (HDL) concentrations (49 vs 45
      mg/dl) (p < 0.01) in 306 obese subjects. Given the stimulatory effect of NPY on
      adipocyte lipoprotein lipase (LPL) activity, and the lack of association of other
      polymorphisms with serum lipid levels, we hypothesize that this is a gain-in
      function polymorphism.

PMID- 12220434
TI  - Genotyping of Israeli infertile men with idiopathic oligozoospermia.
AB  - Microdeletions of the long arm of the Y chromosome involving the azoospermia
      factor (AZF) region are associated with severe oligo- or azoospermia. Abnormal
      androgen receptor (AR) structure or function has also been implicated in male
      infertility. To assess the contribution of these genetic defects to male
      infertility, 61 Israeli men with severe oligo- (n = 15) or azoospermia (n = 46),
      were screened for Y chromosome microdeletions, and the AR-(CAG)n repeat length.
      Fifty fertile Israeli men were similarly analyzed. PCR amplification of 20-54
      simple tag sequences (STSs) located at Yq was used to determine the rate and
      extent of Y chromosome microdeletions. PCR with primers flanking the AR-(CAG)n
      region and subsequent size fractionation on gradient acrylamide gels were used to
      determine AR-(CAG)n length. Five azoospermic individuals (5/61-8.2% and 5/46
      10.8% of azoospermic patients) displayed Y chromosome microdeletions. The mean
      CAG repeat number in infertile men was 18.6 +/- 3.0 compared with 16.6 + 2.7 in
      fertile men (n = 50), a statistically significant difference (p = 0.003). Y
      chromosome microdeletions contribute to male infertility in our azoospermic
      population, and the mean length of the AR-CAG is significantly longer in our
      infertile population than in fertile men.

PMID- 12220435
TI  - Genetic polymorphisms of the apolipoprotein A-IV in a Greek population and their
      relation to plasma lipid and lipoprotein levels.
AB  - Apolipoprotein (apo) A-IV is a protein component of triglyceride-rich
      lipoproteins and high-density lipoproteins (HDL). In this study, two common
      genetic polymorphisms of the apoA-IV gene [codons 347(allele A and T) and 360
      (allele 1 and 2)] were investigated in Greek patients with hyperlipidaemia and in
      healthy individuals matched for age, sex and smoking habits. In both study
      populations we evaluated the effect of these polymorphic sites on lipid and
      lipoprotein plasma levels and the body mass index (BMI). The frequencies of the
      1/1 and 1/2 genotypes in codon 360 were 0.94 and 0.06 in hyperlipidemic patients
      and 0.92 and 0.08 in the control population, respectively. The frequencies of the
      A/A, A/T and T/T genotypes in codon 347 were 0.62, 0.34 and 0.04 in
      hyperlipidemic patients and 0.59, 0.33 and 0.08 in the control population,
      respectively. None of the above genotype frequency differences between the study
      populations reached statistical significance. The control population was not
      affected by any polymorphism of the apo A-IV gene. Hyperlipidaemic patients,
      carriers of the allele 2 (1/2 genotype), had significantly lower plasma
      triglyceride levels than carriers of the allele 1 (p = 0.03). Genetic variation
      in codon 347 had no influence on lipid and lipoprotein plasma levels. None of the
      polymorphisms at codons 360 and 347 affected the BMI. In conclusion, this study
      describes for the first time the genotype frequencies for polymorphic sites in
      codons 360 and 347 of the apo A-IV gene in a Greek population and suggests that
      the presence of the allele 2 is associated with lower plasma triglyceride levels
      in hyperlipidaemic patients.

PMID- 12220436
TI  - Bronchomalacia associated with pulmonary atresia, ventricular septal defect and
      major aortopulmonary collateral arteries, and chromosome 22q11.2 deletion.
AB  - Respiratory distress is one of the major complications in young infants with
      pulmonary atresia, ventricular septal defect and major aortopulmonary collateral
      arteries (PA-VSD-MAPCA); however, its aetiology remains obscure. We have
      previously reported an association of bronchomalacia with PA-VSD-MAPCA in
      patients with a hemizygous deletion of chromosome 22q11.2 (del.22q11). To clarify
      the clinical relevance of bronchomalacia in patients with PA-VSD-MAPCA and
      del.22q11, we reviewed the clinical and laboratory records of four patients with
      PA-VSD-MAPCA who had del.22q11 and bronchomalacia. External bronchial compression
      by anomalous patterning of the aorta and MAPCA was documented in three of the
      four patients, using combinatorial examination of angiocardiography,
      bronchography, fibreoptic bronchoscopy and magnetic resonance imaging. One of the
      four patients died suddenly of severe respiratory distress at 4 years of age,
      while the remaining three were inoperable for complete surgical repair. Our study
      indicates that bronchomalacia as a result of external vascular compression may be
      an aetiology of early-onset respiratory distress in some patients with PA-VSD
      MAPCA and del.22q11, and can significantly affect the clinical outcome.

PMID- 12220437
TI  - Sibship stability of genotype and phenotype in myotonic dystrophy.
AB  - Myotonic dystrophy (DM1) is caused by an unstable CTG repeat expansion. Despite
      the evidence of birth order effect in congenital DM1, the expansion's dynamics
      among sibships is still unknown. The objective of this study was to determine
      phenotype and CTG repeat size variability in DM1 sibships, and to investigate
      their predictive values. We compared 86 sib pairs for CTG repeat, 61 for age at
      onset and 89 for DM1 phenotype. CTG repeats remained stable for 66 of the 86 sib
      pairs, including 25 of 27 maternal transmissions and 30 of 42 paternal
      transmissions. Variations of less than 10 years in the age at onset were observed
      in 44 of 61 sib pairs, including 16 of 18 maternal transmissions and 19 of 28
      paternal transmissions. The same phenotypic severity or a variation of only one
      class was observed among 86 of the 89 sib pairs, including all of the 35 maternal
      transmissions and 30 of the 33 paternal transmissions. Birth order, intergenesic
      interval, oldest sib's CTG repeat or parental age and CTG repeat did not exert
      any significant influence. These results suggest that genotype and phenotype
      remained stable among sibs, although the paternal origin of the mutation seemed
      to reduce the predictability of the severity.

PMID- 12220438
TI  - ATP binding cassette G5 C1950G polymorphism may affect blood cholesterol
      concentrations in humans.
AB  - ATP binding cassette protein G5 (ABCG5) and G8 (ABCG8) may be involved in the
      regulation of intestinal cholesterol absorption. Therefore, genetic variation at
      these loci may affect blood cholesterol concentrations by influencing dietary
      responsiveness. We studied the association between the ABCG5 C1950G (Gln640Glu)
      polymorphism and blood cholesterol concentrations in 486 subjects and
      responsiveness to dietary cholesterol in 99 participants in dietary trials. Mean
      baseline cholesterol concentrations were 0.65 +/- 0.22 mmol/l higher in 13
      subjects with the G/G genotype than in 473 carriers of the C-allele (95%
      confidence interval 0.22-1.08 mmol/l). The response of serum total cholesterol to
      dietary cholesterol tended to be larger in subjects with the G/G genotype as
      compared with carriers of the C-allele. We suggest that the ABCG5 G/G genotype
      may increase serum cholesterol concentrations and, possibly responsiveness to
      dietary cholesterol in humans. Studies in other populations and experimental
      settings are required to confirm or reject this hypothesis.

PMID- 12220439
TI  - Developing a quality scoring system for epidemiological surveys of genetic
      disorders.
AB  - A prototype database of published articles containing data on the frequency of
      human inherited disorders has been developed for use in clinical contexts, in
      medical research, for epidemiological studies, and in the planning of genetic
      services. It can be accessed at http://www.uwcm.ac.uk/uwcm/mg/fidd/. The
      information available in the literature comes from a wide range of publications,
      not all can be described primarily as epidemiological surveys. A preliminary
      assessment indicated that the quality of published articles was highly variable.
      Very few published articles describe quality-scoring systems for epidemiological
      surveys in general. We have developed a new scoring system to assess the quality
      of published articles on genetic disease frequency based on five main criteria
      and nine component scores. We carried out a first pilot study, to test its
      feasibility, usefulness and reproducibility. Eleven assessors scored six papers
      on the epidemiology of Huntington disease. As a result of these findings, we
      modified the scoring system to define each component more clearly. This was then
      evaluated in a second pilot study, which utilized six assessors to score 20
      papers. The consensus between assessors remained relatively poor. We feel that
      while it may be possible to improve the scoring system further, the degree of
      improvement attainable may be limited by the poor standards of content and
      presentation of published surveys, which led to confusion and uncertainty by
      assessors. This pilot exercise has shown the need to raise the awareness of
      researchers and clinicians about the basic quality standards to be required of
      epidemiological genetic surveys.

PMID- 12220440
TI  - Lack of association between methylenetetrahydrofolate reductase (MTHFR) C677T and
      ischaemic heart disease (IHD): family-based association study in a Spanish
      population.
AB  - The effect of the C677T polymorphism in the methylenetetrahydrofolate reductase
      (MTHFR) gene, traditionally associated with ischaemic heart disease (IHD), was
      assessed in a Spanish population. The transmission disequilibrium test (TDT) was
      used to determine a possible association in a sample of 101 trios of IHD
      patients. The distribution of MTHFR genotypes was similar in the IHD subjects and
      the parental group; the TT genotype was present in 14.9% of IHD patients, as
      compared to 15.2% in the parents. The frequency of the T allele was also similar
      in IHD cases and parents (39.6% vs. 42.4%; p = 0.649). The TDT confirmed that the
      observed transmission of the T allele did not deviate significantly from the
      expected one (chi2 = 0.743; p > 0.4). Our TDT analysis clearly demonstrates a
      lack of association between the T allele of the C677T mutation in MTHFR and
      cardiovascular artery disease, both for the general group and for different risk
      subgroups (smokers, hypertension, male sex, overweight and type A behaviour
      pattern) in the Spanish population.

PMID- 12220441
TI  - Apolipoprotein molecular variation in Moroccan Berbers: pentanucleotide (TTTTA)n
      repeat in the LPA gene and APOE-C1-C2 gene cluster.
AB  - Apolipoprotein LPA, APOE, APOC1, and APOC2 genotype frequencies have been
      determined for the first time in a North African population. A sample of 140
      Berber individuals from the Moroccan Moyen Atlas region has been analyzed.
      Allelic and haplotypic data have been used to compare our sample with other world
      populations and the results clearly differentiate Berbers from Europeans and Sub
      Saharans, suggesting several distinctive features of Moroccan Berbers as the
      extreme high values of LPA PNR*11 pentanucleotide allele (10.5%) and the
      relatively high and low values of APOE*E4 (15.7%) and *E2 (4.5%) in comparison to
      other Mediterraneans. Another remarkable result is the frequency distribution of
      the two APOC2 alleles (70% vs 30%) in comparison with the European pattern (50%
      of each allele). The high values of APOE*E4 and LPA PNR*7 together with the
      intermediate linkage disequilibrium values between APOE and APOC1 alleles in
      comparison with Europeans and Africans suggest a certain degree of Sub-Saharan
      influence in the current Moroccan population.

PMID- 12220442
TI  - Comparison of two different protocols of neonatal screening for cystic fibrosis.
AB  - The results of two different protocols of neonatal cystic fibrosis (CF) screening
      in the Lazio region of Italy are reported. The first study, conducted from 1992
      to 2000 on about 200,000 newborns, consisted of an immunoreactive trypsin (IRT)
      protocol without mutation analysis of the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene, referred to as the IRT/IRT protocol.
      Approximately 5% of the newborns with a positive first IRT test were also
      positive at the second test; approximately 57% of the newborns with a high IRT
      level at the second test were subsequently found to be affected by CF. In
      September 1998, a second protocol that included mutation analysis (IRT/DNA/IRT
      protocol) was started. Comparison of the two different screening protocols in
      terms of sensitivity in detecting CF patients demonstrated that the IRT/DNA/IRT
      protocol is more effective because it is able to detect a higher number of CF
      patients than the IRT/IRT protocol. In the same period, in addition to the
      overall diagnosis performed on a screening basis, 64 other subjects were
      identified as being affected by CF on the basis of symptomatic findings. The
      overall incidence of CF (screening + symptoms) was 1 : 2982, while that for
      carriers was 1 : 27. The sensitivity of the screening program increased over the
      period from 1992 to 2000, with the enhanced sensitivity in the past 2 years being
      due to the introduction of the IRT/DNA/IRT protocol.

PMID- 12220443
TI  - Normal levels of soluble transferrin receptor in Friedreich ataxia.

PMID- 12220444
TI  - Familial hypocalciuric hypercalcaemia in a large family with neurofibromatosis 1.

PMID- 12220445
TI  - A novel mutation (N32K) of GLUT2 gene in a Japanese patient with Fanconi-Bickel
      syndrome.

PMID- 12220446
TI  - Epigenetic contributors to the discordance of monozygotic twins.
AB  - Human monozygotic (MZ) twins estimated to occur once in 250 live births, result
      from an errant decision by embryonic cell(s) to develop as separate embryos. They
      are considered genetically identical and any phenotypic discordance between them
      has been used to implicate the role of environment. More recent literature,
      however, has questioned these assumptions but the frequency and the nature of any
      genetic discordance between MZ twins remains poorly understood. We will review
      published cases of phenotypic and genetic discordance between monozygotic twins
      to argue that not all discordance between such twins is due to differences in
      environment. The causes of reduced concordance between MZ twins remains poorly
      understood. They represent among the challenging aspects of the genetics of
      complex multi-factorial traits and diseases. A number of questions regarding the
      published results on MZ twins merit a re-assessment in the light of modern
      molecular insight of the human genome. Such an assessment is needed in directing
      future studies on MZ twins. In particular, we will deal with the origin,
      development, genetic and epigenetic factors that may have implications in
      discordance of the MZ twin pairs.

PMID- 12220448
TI  - Living with Marfan syndrome III. Quality of life and reproductive planning.
AB  - As individuals with Marfan syndrome are increasingly diagnosed earlier in life
      and prior to life-threatening cardiovascular events, there is opportunity to
      study factors that influence their reproductive planning and quality of life. In
      this study of 174 affected adults, the overall quality of life was reported to be
      adequate, although it was significantly decreased within the
      spiritual/psychological domain. Approximately 62% agreed that having Marfan
      syndrome significantly affected their reproductive decision-making. This view was
      correlated with age of diagnosis, mitral valve prolapse, and the view that Marfan
      syndrome has adverse consequences on life. Sixty-nine percent reported personal
      interest in prenatal testing for Marfan syndrome. Respondents most commonly cited
      increased worries about personal health and the recurrence risk as ways that
      Marfan syndrome affects their reproductive decisions. Age, striae, back pain, and
      low quality of life were each independently correlated with lack of sex drive.
      These results affirm the importance of both clinical and psychosocial issues on
      affected adults' reproductive decision-making and sexual well-being. Genetic
      professionals are ideally positioned to discuss concerns about quality of life
      and reproduction with patients with Marfan syndrome and refer those with
      significant concerns for further evaluation and management.

PMID- 12220449
TI  - Family issues in a psychoeducation group for women with a BRCA mutation.
AB  - Few services exist for women who test positive for BRCA1 and BRCA2 mutations
      despite the distress that they and their families may experience. We present one
      model of a time-limited family-oriented psychoeducation group to provide
      information and support for nine women who received positive test results. We
      report on five family-oriented themes that arose from the discussions: distress
      about possible transmission to children; family conflict about testing; concerns
      about disclosure; different coping styles and decision making; and underlying
      family conflict and unresolved grief. We also include recommendations from these
      women to enhance the services available to families by expanding assessment, and
      providing written literature and contact information. In addition, referrals for
      a psychoeducation group, community support group, or psychotherapy may be useful
      for individuals, couples and families who are considering genetic testing for
      BRCA mutations.

PMID- 12220450
TI  - Interdependent effect of angiotensin-converting enzyme and platelet-activating
      factor acetylhydrolase gene polymorphisms on the progression of immunoglobulin A
      nephropathy.
AB  - In order to investigate the interdependent action of the insertion/deletion
      polymorphism of the angiotensin-converting enzyme (ACE) gene and polymorphism in
      exon 11 (C1136-->T; Ala379Val) of the platelet-activating factor acetylhydrolase
      (PAF-AH) gene, which encodes a functional antagonist of PAF, on the progression
      of immunoglobulin A (IgA) nephropathy, we analysed both polymorphisms in patients
      with primary IgA nephropathy, who were followed-up for longer than 3 years.
      During the follow-up (87.3 +/- 50.0 months), the disease progressed in 38 of the
      191 patients (19.9%). The D allele of the ACE gene in the absence of the T allele
      of the PAF-AH gene did not affect the prognosis [odds ratio (OR), 3.6; 95%
      confidence interval (CI), 0.8-16.4] and neither did the T allele in the absence
      of the D allele (OR, 3.0; 95% CI, 0.4-24.2). However, the presence of both was a
      significant prognostic factor (OR, 6.6; 95% CI, 1.4-31.3). After adjusting for
      other risk factors, the presence of both proved to be an independent risk factor
      (OR, 4.5; 95% CI, 1.6-12.7). These results suggest that the interdependent
      effects of ACE and PAF-AH polymorphisms on the progression of IgA nephropathy
      might be more important than the effect of the individual polymorphisms.

PMID- 12220451
TI  - Increased sensitivity to 4-chloro-m-cresol and caffeine in primary myotubes from
      malignant hyperthermia susceptible individuals carrying the ryanodine receptor 1
      Thr2206Met (C6617T) mutation.
AB  - Malignant hyperthermia (MH) is an autosomal-dominant disorder of skeletal muscle,
      triggered by volatile anaesthetics and depolarizing muscle relaxants. The
      causative defect lies in the control of Ca(2+) release from the sarcoplasmic
      reticulum in skeletal muscle. Numerous mutations have been detected in the
      ryanodine receptor 1 (RyR1) gene, but so far an MH-causative role has only been
      confirmed for 16 human RyR1 mutations. In this report we show that myotubes
      derived from individuals carrying the RyR1 Thr2206Met (C6617T) mutation have an
      abnormal response of the intracellular calcium concentration to 4-chloro-m-cresol
      and to caffeine. Satellite cells were obtained from muscle biopsies of patients
      referred for diagnosing MH. The intracellular calcium concentration in response
      to 4-chloro-m-cresol and to caffeine was investigated by fluorescence calcium
      imaging. In myotubes the half-maximal activation concentration (EC(50)) for 4
      chloro-m-cresol was reduced from 203 micro m (wild type) to 98 micro m
      (Thr2206Met), and for caffeine from 3.8 mm to 1.8 mm. From the reduction of
      EC(50) we conclude that the RyR1 Thr2206Met mutation is pathogenic for MH.

PMID- 12220452
TI  - Anticipation in hereditary breast cancer.
AB  - To determine whether familial breast cancer occurs at a younger age in successive
      generations, we reviewed the clinical records of 435 Ashkenazi women with breast
      cancer referred to our cancer genetic clinic. Ninety-eight who reported a
      maternal history of breast cancer were selected for further investigation. All
      women were genotyped for founder BRCA1/2 mutations (185delAG, 5382insC and
      6174delT). Mean age at dignosis was 55.35 +/- 14.21 years in the maternal
      generation and 48.17 +/- 9.32 years in the daughters (t = - 4.144; p < 0.001).
      Seventeen women carried a BRCA1 mutation and 12 the 6174delT mutation in BRCA2.
      Among carriers of the BRCA1 mutation, mean age at diagnosis in the mothers'
      generation (44 +/- 10.18 years) did not differ from that recorded in the
      daughters (40.76 +/- 76 years). Among BRCA2 mutation carriers and non-carriers,
      the mean age at diagnosis in the daughters' generation (41.4 +/- 7.2 and 50.7 +/-
      8.8 years, respectively) was younger than in the mothers (61.75 +/- 14.1 and
      57.08 +/- 13.7 years, respectively) (t = - 4.29; p < 0.001 for BRCA2 carriers and
      t = -3.76; p < 0.001 for non-BRCA1/2 carriers). Daughters who were carriers of
      BRCA1/2 mutations developed breast cancer at a significantly younger age than non
      carriers, whilst in the mothers' generation, carriers of BRCA1 mutations
      developed breast cancer at a significantly younger age than carriers of BRCA2
      mutations and non-carriers. BRCA1 mutations predispose to breast cancer at an
      early age in both mothers and daughters, whereas mutations in BRCA2 were
      associated with significantly younger age at diagnosis in the second generation.
      This observation could be related to gene-environmental interactions causing
      anticipation in BRCA2 mutation carriers.

PMID- 12220453
TI  - Haplotype analysis of a BRCA1: 185delAG mutation in a Chilean family supports its
      Ashkenazi origins.
AB  - At least 25% of Ashkenazi Jewish families with two or more cases of premenopausal
      breast cancers are attributable to one of three founder mutations in BRCA1 or
      BRCA2. As these three founder mutations are common in the Ashkenazi Jewish
      population ( approximately 2.5%) and can easily be tested for in a multiplex
      assay, establishing ethnicity can expedite genetic testing. It is not always
      possible, however, to conclusively establish ethnicity before offering testing.
      We report here the occurrence of a founder Ashkenazi Jewish BRCA1 mutation,
      185delAG (also known as 187delAG), in a non-Jewish Chilean family with no
      reported Jewish ancestry. The linked haplotype present in this family was
      identical to that identified in the Ashkenazi Jewish population. This case report
      not only illustrates the problem of the definition of ethnicity but also points
      to the possibility of further studies of the frequency of founder Ashkenazi
      Jewish mutations in populations not generally considered to be of Ashkenazi
      Jewish origin.

PMID- 12220454
TI  - Craniofacial features in Cohen syndrome: an anthropometric and cephalometric
      analysis of 14 patients.
AB  - Cohen syndrome (Mendelian Inheritance in Man [MIM] no. 216550) is a rare,
      autosomal-recessive inherited disorder with mental retardation and a typical
      appearance. The condition is relatively common in Finland where 35 patients have
      been diagnosed. We studied 22 patients in detail, obtaining anthropometric
      measurements of the head and face, and cephalometric radiographs of 14 patients
      (14-57 years of age). Measurements of patients were compared to population norms
      and matched controls. Anthropometric analysis confirmed and quantified the
      previously described syndrome features: small head size [-4 standard deviations
      (SD)], with varying cephalic index. Width of the upper face was close to normal,
      but width of the lower face was small. Philtrum length was shorter than in
      healthy controls (p = 0.0039 in females and p = 0.0014 in males). The
      measurements from standardized radiographs revealed short cranial base dimensions
      (-2.2 and -2.6 SD), but normal cranial base angles. Prognathism of jaws was
      within normal limits. Reduced head size (microcephaly), short philtrum and small
      cranial base dimensions are essential features in Cohen syndrome. In addition,
      most patients had forward-inclined upper incisors and maxillary prognathia. We
      conclude that exact measurements mostly confirmed the Cohen syndrome description
      based previously on clinical impression.

PMID- 12220455
TI  - Spinal muscular atrophy in black South Africans: concordance with the universal
      SMN1 genotype.
AB  - Only one study has reported on the genetic basis of spinal muscular atrophy (SMA)
      in South African subjects. This was conducted in the Johannesburg region and has
      suggested that black South Africans only (indigenous Africans) differ from the
      norm. We have explored this further by DNA studies in 30 unrelated and racially
      diverse patients who reside in the Western Cape, and who were assessed as SMA
      subjects according to the internationally accepted inclusion criteria for SMA.
      These subjects were seen at the neurology clinic at Red Cross Children's Hospital
      in Cape Town during the period 1980-2001. Four had the type 1 form of SMA, 16 had
      type 2 and 10 had type 3. All patients were found to be homozygous for the loss
      of either exon 7 or exons 7 and 8 of the SMN1 gene. Six additional patients had
      anterior horn cell disease but were negative for the SMN1 gene deletion. All six
      had exclusion features listed in the international guidelines. This study shows
      that all patients from the Western Cape, which included 12 black South Africans,
      are no different genetically or phenotypically from the internationally
      recognized form of typical SMA.

PMID- 12220456
TI  - Three novel mutations of the PKD1 gene in Korean patients with autosomal dominant
      polycystic kidney disease.
AB  - Mutations at the PKD1 locus account for 85% of cases of the common genetic
      disorder called autosomal dominant polycystic kidney disease (ADPKD). Screening
      for mutations of the PKD1 gene is complicated by the genomic structure of the 5'
      duplicated region encoding 75% of the gene. To date, more than 90 mutations of
      the PKD1 gene have been reported in the European and American populations, and
      relatively little information is available concerning the pattern of mutations
      present in the Asian populations. We looked for mutations of the PKD1 gene in 51
      unrelated Korean ADPKD patients, using polymerase chain reaction (PCR) with
      primer pairs located in the 3' single-copy region of the PKD1 gene and by single
      strand conformation polymorphism (SSCP) analysis. We found three novel mutations,
      a G to A substitution at nucleotide 11012 (G3601S), a C to A substitution at
      nucleotide 11312 (Q3701X), and a C to T substitution at nucleotide 12971
      (P4254S), and a single polymorphism involving a G to C substitution at nucleotide
      11470 (L3753L). These mutations were not found in control individuals, and no
      other mutations in the 3' single-copy region of the PKD1 gene of patients with
      these mutations were observed. In particular, P4254S segregated with the disease
      phenotype. The clinical data of affected individuals from this study, and of
      previously reported Korean PKD1 mutations, showed that patients with frameshift
      or nonsense mutations were more prone to develop end-stage renal failure than
      those with missense mutations. Our findings indicate that many different PKD1
      mutations are likely to be responsible for ADPKD in the Korean population, as in
      the Western population.

PMID- 12220457
TI  - alpha1-Antitrypsin null alleles: evidence for the recurrence of the L353fsX376
      mutation and a novel G-->A transition in position +1 of intron IC affecting
      normal mRNA splicing.
AB  - alpha1-Antitrypsin (PI) deficiency is a common autosomal recessive disorder
      associated with emphysema and liver disease, which may result from a wide
      spectrum of mutations causing a reduction of serum levels (deficient alleles) or
      a total lack of circulating protein (null alleles). We report two different
      alleles associated with the absence of isoelectric focusing banding patterns in
      Portuguese patients with emphysema. The first allele, Q0(ourem), results from the
      recurrence of the defining mutation of the Q0(mattawa) variant (L353fsX376) on a
      M3 normal background. The second allele, Q0(porto), has a novel G-->A mutation at
      position +1 of the intron IC (IVS1C+1G-->A), which restricts mononuclear
      phagocyte transcripts to mRNA species resulting from the direct splice of exon IA
      to exon II. The absence of this normal splice alternative in the liver, where PI
      is primarily synthesized, provides a basis for the pathogenic effects of this
      mutation.

PMID- 12220458
TI  - Gene conversion (655G splicing mutation) and the founder effect (Gln318Stop)
      contribute to the most frequent severe point mutations in congenital adrenal
      hyperplasia (21-hydroxylase deficiency) in the Spanish population.
AB  - This study addresses the contributions of gene conversion and a founder effect to
      the distribution of the two most frequent severe point mutations of the 21
      hydroxylase (21OH) gene causing congenital adrenal hyperplasia: the 655G splicing
      mutation at intron 2, and Gln318Stop in a Spanish population. Direct and indirect
      analyses of segregated mutant and normal 21OH genes in 200 Spanish families
      (classic and nonclassic 21OH deficiency) were performed. Both mechanisms were
      found to contribute to different degrees to the defective investigated alleles.
      The 655G splicing mutation (62 alleles, 15.5%) seemed to be almost exclusively
      related to recent conversion events, whereas Gln318Stop (33 alleles, 8.3%) is
      more likely to be due to the dissemination of remotely generated mutant alleles.
      Other severe defective alleles, 8 bp-deletion (13 alleles, 3.3%), 306insT (5
      alleles, 1.3%), and gene deletions (43 alleles, 11%), as well as the mild
      mutation Val281Leu (120 alleles, 30%), also appear to be strongly associated with
      particular D6S273 alleles. Although gene conversion contributes to the generation
      of severe 21OH alleles, the high frequency of some severe mutations in different
      geographic areas is consistent with a founder effect.

PMID- 12220459
TI  - How many phenotypes in the DTDST family chondrodysplasias?

PMID- 12220460
TI  - Increased permeability of asthmatic epithelial cells to pollutants. Does this
      mean that they are intrinsically abnormal?

PMID- 12220461
TI  - The role of neurotrophins in the pathogenesis of asthma and related diseases:
      allergy and asthma as prototypic neuro-immune diseases?

PMID- 12220462
TI  - The Cochrane Collaboration and its contribution towards the management of
      allergic diseases.

PMID- 12220463
TI  - Comparison of bronchial responsiveness to histamine in asthma, allergic rhinitis
      and allergic sensitization at the age of 7 years.
AB  - BACKGROUND: Bronchial responsiveness (BR) to histamine or methacholin is a common
      finding in adult non-asthmatic patients with allergic rhinitis. OBJECTIVE: We
      tested whether BR is also present in children with a comparatively short history
      of allergic rhinitis in a paediatric cohort. METHODS: We performed pulmonary
      function tests and histamine challenges in a total of 654 children (age 7 years,
      participants of the German Multicenter Allergy Study) and compared PC20 FEV1
      values in children with asthma, allergic rhinitis, asymptomatic allergic
      sensitization and non-atopic controls. RESULTS: Most pronounced BR to histamine
      was observed in allergic asthmatics (n = 28), irrespective of the presence or
      absence of allergic rhinitis. Furthermore, PC(20)FEV(1) values in non-asthmatic
      children with allergic rhinitis (n = 24) were not significantly different from
      those seen in asymptomatic atopic (n = 54) or non-atopic controls (n = 92).
      CONCLUSIONS: In contrast to adult study populations, 7-year-old non-asthmatic
      children with allergic rhinitis do not show a higher degree of BR than
      asymptomatic atopic or non-atopic controls. Therefore, secondary preventive
      measures in non-asthmatic children with allergic rhinitis (such as regular local
      anti-inflammatory therapy or specific immunotherapy) should be studied and
      applied more intensely to prevent bronchial hyper-responsiveness (BHR) and asthma
      in this high-risk group.

PMID- 12220464
TI  - Clinical and immunologic factors associated with the presence or absence of
      airways hyper-responsiveness in childhood asthma.
AB  - BACKGROUND: During the baseline period of a clinical trial comparing different
      dosage schedules of inhaled steroids, asthmatic children (aged 6-10 years) were
      expected to meet the inclusion criterion of airways hyper-responsiveness (PD(20)
      methacholine < 80 micro g) after withdrawal of inhaled corticosteroids for 2-8
      weeks. However, many children failed to do so. OBJECTIVE: It has been shown that
      young wheezing children may outgrow their symptoms. We investigated if
      differences between children with and without airways hyper-responsiveness after
      withdrawal of inhaled corticosteroids were compatible with differences between
      transient and persistent wheezers found in other studies. METHODS: Seventy-eight
      children entered the study, of which 41 developed airways hyper- responsiveness
      after withdrawal of inhaled corticosteroids, and 37 did not. These two groups of
      children were compared with respect to differences in demographic, clinical, and
      immunological features (IL-4, IL-5, IL-10, and IFN-gamma produced by Con A
      stimulated peripheral mononuclear cells (PBMCs) and serum IL-4, IL-5 and soluble
      intercellular adhesion molecule-1 (sICAM-1)). RESULTS: Hyper-responsive children
      had more atopic features (positive RAST, high IgE, eczema), lower levels of FEV1
      and lower concentrations of sICAM-1 than non-hyper-responsive children. Apart
      from a borderline significantly higher IL-4 production in the hyper-responsive
      group, other immunologic parameters were comparable. Multivariate logistic
      regression analysis showed that high serum IgE, low FEV1, and low sICAM-1 levels
      were independently associated with the presence of airways hyper-responsiveness
      after stopping inhaled corticosteroids. Atopy was associated with higher
      concentrations of IL-4 in the hyper-responsive group. CONCLUSION: After
      withdrawal of inhaled corticosteroids many children previously diagnosed with
      asthma did not develop airways hyper-responsiveness. We conclude that hyper
      responsive children share features with persistent wheezers as found in previous
      studies, whereas the non-hyper- responsive children may represent transient
      wheezers.

PMID- 12220465
TI  - Effect of ozone and nitrogen dioxide on the permeability of bronchial epithelial
      cell cultures of non-asthmatic and asthmatic subjects.
AB  - BACKGROUND: Although epidemiological as well as in vivo exposure studies suggest
      that ozone (O3) and nitrogen dioxide (NO2) may play a role in airway diseases
      such as asthma, the underlying mechanisms are not clear. OBJECTIVE: Our aim was
      to investigate the effect of O3 and NO2 on the permeability of human bronchial
      epithelial cell (HBEC) cultures obtained from non-atopic non-asthmatic (non
      asthmatics) and atopic mild asthmatic (asthmatics) individuals. METHODS: We
      cultured HBECs from bronchial biopsies of non-asthmatics and asthmatics, and
      exposed these for 6 h to air, 10 to 100 parts per billion (p.p.b.) O3, or to 100
      to 400 p.p.b. NO2, and assessed changes in electrical resistance (ER) and
      movement of 14C-BSA across the cell cultures. RESULTS: Although exposure to
      either O3 or NO2 did not alter the permeability of HBEC cultures of non
      asthmatics, 10 to 100 p.p.b. O3 and 400 p.p.b. NO2 significantly decreased the ER
      of HBEC cultures of asthmatics, when compared with exposure to air. Additionally,
      10, 50 and 100 p.p.b. O3 led to a significant increase in the movement of 14C-BSA
      across asthmatic HBEC cultures, after 6 h of exposure (medians = 1.73%; P < 0.01,
      1.50%; P < 0.05 and 1.53%, P < 0.05, respectively), compared with air exposed
      cultures (median = 0.89%). Similarly, exposure for 6 h to both 200 and 400 p.p.b.
      NO2 significantly increased the movement of 14C-BSA across asthmatic HBEC
      cultures, when compared with air exposure. A comparison of data obtained from the
      two study groups demonstrated that 10 to 100 p.p.b. O3- and 200 to 400 p.p.b. NO2
      induced epithelial permeability was greater in cultures of asthmatics compared
      with non-asthmatics. CONCLUSION: These results suggest that HBECs of asthmatics
      may be more susceptible to the deleterious effects of these pollutants. Whether
      in patients with asthma the greater susceptibility of bronchial epithelial cells
      to O3 and NO2 contributes to the development of the disease, or is a secondary
      characteristic of this condition, remains to be determined.

PMID- 12220466
TI  - Total and allergen-specific immunoglobulin A levels in saliva in relation to the
      development of allergy in infants up to 2 years of age.
AB  - BACKGROUND: The association between salivary IgA levels and development of
      allergy is controversial and the employed methodology has been questioned.
      OBJECTIVE: The aim of the study was to relate the levels of total IgA, SIgA and
      allergen-specific IgA antibodies in saliva to the development of allergy in
      infants during the first 2 years of life. METHODS: Saliva samples from 80 infants
      participating in a prospective study regarding the development of allergy were
      collected at 3 or 6, and 12 and 24 months of age. Total IgA, SIgA and Fel d 1 and
      beta-lactoglobulin specific IgA levels were analysed with ELISA. RESULTS: The
      levels of total IgA and SIgA increased with age. The number of samples with
      detectable IgA to Fel d 1 tended to increase with age, whereas the opposite was
      observed for IgA to beta-lactoglobulin. Infants who developed allergy tended to
      have higher levels of total IgA, and allergen-specific IgA was more commonly
      detected than in non-allergic children. In contrast, non-allergic children tended
      to have higher levels of SIgA. Furthermore, the levels of SIgA were higher in
      sensitized infants with no allergic symptoms than in sensitized children with
      symptoms. Infants with allergic parents had lower SIgA levels than infants
      without. Direct exposure to cat and cow's milk did not influence the levels of
      allergen-specific IgA levels, nor was there any association between breast
      feeding and IgA production. CONCLUSION: The kinetics of food and inhalant
      allergen-specific IgA in saliva during the first 2 years of life is similar to
      what has earlier been shown for IgG in serum. Development of allergy tended to be
      associated with high levels of total and allergen-specific IgA antibodies, but
      low levels of SIgA. Furthermore, high levels of SIgA seemed to protect sensitized
      children from developing allergic symptoms during the first 2 years of life,
      supporting a possible protective role of SIgA against development of allergy.

PMID- 12220467
TI  - House dust mites and their allergens at selected locations in the homes of house
      dust mite-allergic patients.
AB  - BACKGROUND: Knowledge of the occurrence of house dust mites (HDM) and their
      allergens in domestic locations is important when planning intervention.
      OBJECTIVE: The aim of this study was to describe the distribution of HDMs and
      their allergens before intervention in multiple locations in the homes of newly
      diagnosed HDM-allergic patients with a known high Der 1 concentration in their
      mattress dust. METHODS: Dust was collected from ten locations in the homes of
      eight HDM-allergic patients. Dust was analysed for allergen content with ELISAs
      for Der f 1, Der p 1 and Der m 1; and HDM were counted. Total allergen
      concentrations ( micro g Der 1/g dust) were expressed as the sum of Der f 1, Der
      p 1 and Der m 1. RESULTS: On mattresses the median concentration was 86 micro g
      Der 1/g dust (range 30-288) and 188 mites/g dust (range 12-1910). Der 1 exceeded
      10 micro g/g dust in mattresses (8/8), duvets/pillows (3/8), a bedroom carpet
      (1/1), a living room carpet (1/6), upholstered furniture (2/8) and a curtain
      (1/5). Uncarpeted floors, upholstered furniture, bookshelves and walls had
      significantly lower Der 1 concentration than the mattresses. The relative
      contribution of Der p 1, Der f 1 or Der m 1 to Der 1 was related to homes, rather
      than to the location. Der m 1 only occurred in minute amounts. CONCLUSION: For
      HDM intervention, our results indicate that priority should be given to the
      removal of allergens from mattresses, and in addition from carpets,
      duvets/pillows and upholstered furniture. Dust from walls, uncarpeted floors,
      bookshelves and curtains appear to contribute insignificantly to the domestic HDM
      allergen load.

PMID- 12220468
TI  - Role of environmental exposure to spider mites in the sensitization and the
      clinical manifestation of asthma and rhinitis in children and adolescents living
      in rural and urban areas.
AB  - BACKGROUND: Spider mites such as the citrus red mite and the two-spotted spider
      mite have been demonstrated to be important allergens for fruit cultivating
      farmers. OBJECTIVE: To evaluate the role of environmental exposure to spider
      mites in the sensitization and the clinical manifestations of asthma and rhinitis
      in children and adolescents living in urban and rural areas. METHODS: A total of
      16,624 subjects (aged 7 to 18 years) living in urban (metropolitan and non
      metropolitan) and rural areas (apple orchards and citrus orchards) in Korea were
      evaluated by questionnaire and skin prick test for 11 common aeroallergens,
      including citrus red mite (CRM) and two-spotted spider mite (TSM). RESULTS: The
      positive skin response rates to TSM were 4.2% of 1,563 metropolitan subjects,
      3.8% of 5,568 non-metropolitan subjects and 6.5% of 1,464 subjects living nearby
      apple farms, and that to CRM 15.6% of 8,029 living nearby citrus farms. The
      prevalence of current wheeze and rhinitis as reported on a questionnaire was
      higher among those with a history of visiting fruit farms once or more per year
      than among those without it (10% vs. 7.1%, 32.8% vs. 26.7%, for wheezing and
      rhinitis, respectively). Among those with wheezing or rhinitis, the positive skin
      responses to TSM or CRM were also higher among those with a history of visiting
      fruit farms than among those without one (11.2% vs. 6.6%, 13.0% vs. 6.6%,
      respectively), although the positive skin responses to house dust mites were
      similar in the both groups. CONCLUSION: Spider mites are common sensitizing
      allergens in children and adolescents exposed to them, and environmental exposure
      to these mites may represent an important risk factor in the sensitization and
      the clinical manifestations of asthma and rhinitis in children and adolescents
      living in rural and urban areas.

PMID- 12220469
TI  - Relationship between allergic rhinitis, disturbed cognitive functions and
      psychological well-being.
AB  - BACKGROUND: Symptomatic allergic rhinitis reduces quality of life as a result of
      the symptoms experienced and possibly as a result of impaired psychological well
      being and cognitive functioning. Few investigations have measured cognitive
      functions objectively and it remains uncertain whether allergic rhinitis leads to
      an objective reduction in cognitive functions. OBJECTIVE: To evaluate the
      relationship between symptomatic allergic rhinitis, cognitive functions and
      psychological well-being. Differences between subjective and objective cognitive
      impairments were evaluated. METHODS: The cognitive functions (working memory,
      memory retrieval, speed of information processing and flexibility of information
      processing) and psychological well-being of 26 patients with symptomatic allergic
      rhinitis and 36 healthy controls matched for intelligence, education, age and sex
      were compared. The influence of education, intelligence, sex and age was
      considered. RESULTS: Overall, psychological well-being was significantly impaired
      in the patient group, as shown by higher scores in feelings of insufficiency,
      complaints of somatization, sleep disturbances and depressive feelings, whereas
      cognitive function was not. CONCLUSIONS: Allergic rhinitis was related to
      significantly impaired psychological well-being and to perceived impaired
      cognitive functioning. However, no significant objective impairment of cognitive
      functioning was found. Allergic patients may temporarily put more effort into
      sustaining performance, resulting in earlier exhaustion, which is not noticed
      during assessment but which impairs psychological well-being.

PMID- 12220470
TI  - Evidence for the genetic control of immunoglobulin E reactivity to the allergens
      of Alternaria alternata.
AB  - BACKGROUND: The fungus Alternaria alternata contains potent allergens, and
      sensitization to these allergens is associated with a high risk of respiratory
      disease. The influence of genetic regulation on sensitization to Alternaria is
      unknown. OBJECTIVE: To determine the influence of genetic factors on IgE
      responses to specific allergens of Alternaria. METHODS: The concordance of skin
      prick test (SPT), radioallergosorbent test (RAST) and IgE-binding profiles of
      sera were examined from a large cohort of monozygotic and dizygotic twins.
      RESULTS: Casewise concordance for a positive SPT response was monozygous (MZ)
      66%: dizygous (DZ) 40% (P = 0.002). Logistic regression confirmed that casewise
      concordance was significantly stronger between MZ than DZ pairs. Immunoblotting
      against an Alternaria extract revealed 19 allergenic bands. The differences in
      concordance between the different bands were not significant for either the MZ (P
      = 0.97) or DZ (P = 0.84) groups. The pooled MZ : DZ difference in concordance was
      just significant (P = 0.049), suggesting an overall genetic effect on the
      response to Alternaria. This was reinforced by the comparison of the MZ and DZ
      correlations for total number of bands recognized (MZ r = 0.65; DZ r = 0.37, P =
      0.015). Overall, there was a moderate correlation between the individual SPT weal
      size and RAST score (r(2) = 0.41) and a substantial correlation between the
      number of immunoblotted bands and RAST scores (r(2) = 0.79). CONCLUSION: There is
      a strong genetic influence on IgE response to the mixture of Alternaria allergens
      and a lesser effect on IgE response to individual allergens.

PMID- 12220471
TI  - Use of a chimeric ELISA to investigate immunoglobulin E antibody responses to Der
      p 1 and Der p 2 in mite-allergic patients with asthma, wheezing and/or rhinitis.
AB  - BACKGROUND: Sensitization to indoor allergens, particularly to dust mites, is a
      strong risk factor for asthma in children and adults. Assessment of sensitization
      is carried out using in vivo and in vitro tests to detect specific IgE
      antibodies. OBJECTIVE: To investigate IgE antibody responses to mites in patients
      with asthma, wheezing and/or rhinitis, using chimeric ELISA to measure specific
      IgE antibodies to mite allergens Der p 1 and Der p 2. METHODS: Specific IgE
      antibodies to Der p 1 and Der p 2 were quantified by chimeric ELISA, and compared
      with IgE to Dermatophagoides pteronyssinus (Dpt) measured using the CAP system
      (Pharmacia). A panel of sera from 212 patients with asthma, wheezing and/or
      rhinitis and 11 controls was analysed. RESULTS: There was a significant
      correlation between IgE to Dpt measured by CAP and IgE to Der p 1 (r = 0.81, P <
      0.001), Der p 2 (r = 0.79, P < 0.001) and combined Der p 1 and Der p 2 (r = 0.86,
      P < 0.001). Seventy per cent of all patients had IgE to Dpt, and of those, 76.5%
      had IgE to Der p 1, 79.2% had IgE to Der p 2 and 83.1% had IgE to Der p 1 and Der
      p 2 combined. Considering the cut-off level of 2 IU/mL of IgE to either Der p 1
      or Der p 2, the predictive value for a positive IgE to Dpt by CAP was greater
      than 95%. CONCLUSIONS: The chimeric ELISA allowed accurate quantification of IgE
      antibodies to Dpt allergens Der p 1 and Der p 2, and it could be useful for
      studying immune responses to mites in patients with asthma and/or rhinitis.

PMID- 12220472
TI  - Molecular and immunological characterization of a novel timothy grass (Phleum
      pratense) pollen allergen, Phl p 11.
AB  - BACKGROUND: Allergy to grass pollen is typically associated with serum IgE
      antibodies to group 1 and/or group 5 allergens, and additionally often to one or
      several less prominent allergens. Most of the grass pollen allergens identified
      to date have been characterized in detail by molecular, biochemical and
      immunological methods, timothy grass being one of the most thoroughly studied
      species. However, a 20-kDa allergen frequently recognized by IgE antibodies from
      grass pollen allergics has so far escaped cloning and molecular characterization.
      OBJECTIVE: To clone and characterize the 20 kDa timothy grass pollen allergen Phl
      p 11. METHODS: Phl p 11 cDNA was cloned by PCR techniques, utilizing N-terminal
      amino acid sequence obtained from the natural allergen. Phl p 11 was expressed as
      a soluble fusion protein in Escherichia coli, purified to homogeneity and used
      for serological analysis and to study Phl p 11 specific induction of histamine
      release from basophils and skin reactivity in sensitized and control subjects.
      RESULTS: Phl p 11 cDNA defined an acidic polypeptide of 15.8 kDa with homology to
      pollen proteins from a variety of plant species and to soybean trypsin inhibitor.
      The sequence contained one potential site for N-linked glycosylation. Serological
      analysis revealed that recombinant Phl p 11 shared epitopes for human IgE
      antibodies with the natural protein and bound serum IgE from 32% of grass pollen
      sensitized subjects (n = 184). Purified recombinant Phl p 11 elicited skin
      reactions and dose-dependent histamine release from basophils of sensitized
      subjects, but not in non-allergic controls. CONCLUSION: As the first
      representative of group 11 grass pollen allergens, Phl p 11 has been cloned and
      produced as a recombinant protein showing allergenic activity. One-third of grass
      pollen-sensitized subjects showed specific IgE reactivity to recombinant Phl p
      11, corresponding in magnitude to a significant proportion of specific IgE to
      grass pollen extract.

PMID- 12220473
TI  - Non-allergenic antigen in allergic sensitization: responses to the mite ferritin
      heavy chain antigen by allergic and non-allergic subjects.
AB  - BACKGROUND: The majority of house dust mite proteins are non-allergenic. There
      is, however, no information on the type of immune responses produced to these
      proteins and if the responses are affected by allergic sensitization. OBJECTIVE:
      To identify and produce a non-allergenic antigen of the house dust mite and
      compare antibody and T cell responses with the responses to allergens in
      sensitized and non-sensitized individuals. RESULTS: Ferritin heavy chain was
      cloned from a cDNA library as a candidate non-allergen of the house dust mite. It
      bound IgG but not IgE in the sera of allergic and non-allergic subjects and
      induced high T cell proliferative responses that correlated highly with the
      responses to the major allergen Der p 2. The cytokine response to the non
      allergen was characterized by the release of high levels of both Th1 and Th2
      cytokines from the PBMC of both allergic and non-allergic subjects. In contrast,
      the response to Der p 2 showed the expected high level of Th2 cytokine release
      from the PBMC of allergic subjects, while the Th2 cytokine production from PBMC
      of non-allergic subjects was low and even lower than that induced by ferritin
      heavy chain. The levels of IFN-gamma release were similar for all groups. Der p 2
      induced significantly more IL-10 than ferritin in the non-allergic group.
      CONCLUSION: The T cell responses to a non-allergenic protein of the house dust
      mite were high and strongly correlated with the response to the major allergen.
      The non-allergenic protein induced high levels of Th1 and Th2 cytokine in both
      allergic and non-allergic subjects, while the allergen induced high levels of Th2
      cytokine in allergic subjects and low levels in non-allergic subjects. The
      responses to the allergen were thus independently up- and down-regulated with no
      evidence of bystander regulation.

PMID- 12220474
TI  - Activation of the specific neurotrophin receptors TrkA, TrkB and TrkC influences
      the function of eosinophils.
AB  - BACKGROUND: Recent studies have shown that nerve growth factor (NGF) can act on
      several immune cells as well as residential cells. But little is known about
      their role in modulating eosinophil function via activation of high-affinity
      receptors. OBJECTIVES: The aim of this study was to assess whether eosinophils
      express functional receptors and if their function is influenced by NGF, brain
      derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3). METHODS: Eosinophils
      were purified by negative immunoselection (purity > 96%). High-affinity
      neurotrophin receptors were demonstrated by reverse transcription polymerase
      chain reaction, western blotting and flow-cytometry analysis. Functionality of
      receptors was demonstrated by receptor phosphorylation after ligand binding.
      Eosinophils were incubated with NGF, BDNF and NT-3, and cells and supernatants
      were collected for measurement of the mediators IL-4, IL-5, IL-8, transforming
      growth factor (TGF)-beta1, eosinophil cationic protein (ECP), eosinophil protein
      X (EPX) as well as eosinophil viability. RESULTS: Eosinophils expressed mRNA for
      neurotrophin receptors. Proteins were detectable by western blot and fluorescent
      activated cell sorter analysis. The receptors were phosphorylated after
      stimulation with neurotrophins. After NGF stimulation, a significant increase in
      IL-4 was detectable. BDNF and NT-3 stimulation led to a significant increase in
      EPX. Eosinophil viability was not influenced. CONCLUSIONS: Eosinophils express
      the functionally active receptors TrkA, TrkB and TrkC. Receptor activation
      stimulates eosinophils. This might be an additional pathway regulating
      inflammatory responses in allergic reactions.

PMID- 12220475
TI  - Evaluation of serum eosinophil cationic protein as a predictive marker for asthma
      exacerbation in patients with persistent disease.
AB  - BACKGROUND: Eosinophilic inflammation is a feature of asthma. However,
      serological markers to indicate eosinophil activation in this process are not
      fully defined. OBJECTIVE: To evaluate the relationship of serum eosinophil
      cationic protein (ECP) to asthma worsening and a marker for treatment
      effectiveness, 26 adult patients with an asthma exacerbation were identified.
      METHODS: Identified asthma subjects were treated with oral corticosteroids
      (prednisone) for 14 days. The lung function variables, forced expiratory volume
      in one second (FEV1) and peak expiratory flow (PEF), were determined as
      percentage of predicted and the blood total eosinophil count and serum ECP levels
      were measured. Patients were re-evaluated after 14 days of corticosteroid
      treatment and then every 3 months thereafter during a 12-month period. RESULTS:
      Eighteen patients responded to prednisone treatment, whereas eight did not,
      assessed as improvement of their lung function parameters. Different serum ECP
      patterns could be seen in the responders compared with the non-responders. All 18
      responders had considerably increased serum ECP at the time of exacerbation,
      whereas the non-responders had lower serum ECP levels. The serum ECP levels
      decreased to a greater extent in the responder patient group than in the non
      responder patients following prednisone treatment. This difference in patterns
      was not seen with total blood eosinophil counts. CONCLUSION: Our findings suggest
      that serum ECP may be used to predict a response to corticosteroid therapy in
      adult patients with asthma.

PMID- 12220476
TI  - Protection against exercise-induced bronchoconstriction by montelukast in aspirin
      sensitive and aspirin-tolerant patients with asthma.
AB  - BACKGROUND: Montelukast, a cysteinyl-leukotriene receptor antagonist, was
      reported to have a protective effect against exercise-induced bronchoconstriction
      (EIB). Aspirin-induced asthma (AIA) is characterized by overproduction of
      cysteinyl-leukotrienes. OBJECTIVE: The aim of the study was to compare the
      response to exercise and the effect of montelukast on EIB in AIA as compared to
      aspirin-tolerant asthma (ATA). METHODS: A placebo-controlled, double blind, cross
      over randomized study was performed in 19 AIA and 21 ATA patients with stable
      asthma. A single dose of montelukast (10 mg) or placebo (PL), was given orally
      one hour prior to exercise challenge. FEV1 was measured before and 5, 10, 15 min
      after exercise and then at 15-minute intervals for 4 h. Urinary LTE4 excretion
      and blood eosinophil count were measured at baseline, 2 h and 4 h following
      exercise challenge. RESULTS: Positive bronchial response to exercise was observed
      in 47.5% of all patients studied. Exercise led to almost identical maximal fall
      in FEV1 in AIA and ATA patients (23.5% +/- 6.8% vs. 21.8% +/- 12.0%,
      respectively; P = 0.7). Montelukast, as compared to PL, significantly attenuated
      EIB in 63.2% of 19 patients with positive exercise test preceded by PL. The mean
      of maximum fall in FEV1 from the pre-exercise value was 10.2% +/- 13.8 after
      montelukast as compared to 22.5% +/- 10.2 after placebo (P < 0.001). No
      significant differences between protective effect of montelukast was observed in
      AIA as compared to ATA patients (P = 0.63, anova). Urinary LTE4 excretion showed
      no change following exercise, irrespective of the result of the test in all
      subjects. CONCLUSION: Patients with AIA and ATA react similarly to exercise
      challenge and obtain similar protection against EIB by montelukast.

PMID- 12220477
TI  - The accuracy of the diagnosis of suspected paracetamol (acetaminophen)
      hypersensitivity: results of a single-blinded trial.
AB  - BACKGROUND: Hypersensitivity to paracetamol (acetaminophen) is rare and very few
      clinical data are available in the literature. MATERIALS AND METHODS: Eighty-four
      patients (28 males and 56 females, 5-70 years old) with a suspicion of
      paracetamol hypersensitivity were referred to our drug allergy clinic between May
      1996 and May 2000. The reaction had occurred 1-96 months prior to the
      consultation. Single-blinded placebo-controlled oral challenges were carried out
      in 82 patients, under strict hospital surveillance. RESULTS: Most of the patients
      experienced skin eruptions 82/84 (97.6%), with 10 cases of anaphylactic shock
      (11.9%). Twenty-six (30.9%) reactions were immediate (occurring within the first
      hour after drug intake), 53 (63.1%) non-immediate and five could not remember.
      Oral provocation tests (OPT) demonstrated drug hypersensitivity in 11 patients
      only. The two patients not tested (due to a history of life-threatening reaction)
      were included in the positive group. Thus, 13 (15.5%) patients had paracetamol
      hypersensitivity and 71 (84.5%) had not. All the 13 positive patients had skin
      eruptions, five with anaphylactic shock. 9/13 had immediate reactions. Using OPT,
      10 out of 11 had the same clinical reaction but more delayed. In both groups,
      whether hypersensitive to paracetamol or not: atopy was similar (7/13-53.8% and
      31/71-43.7%), sex ratio was not different (M/F 0.3 and 0.5), 3/13 (23.1%) and
      0/71 (0%) had aspirin/ibuprofen hypersensitivity. CONCLUSION: The clinical
      history of paracetamol (acetaminophen) hypersensitivity is rarely sufficient to
      set a firm diagnosis and only OPT can confirm this. Careful OPT reproduces the
      same symptoms (not more severe in our hands) with the same or slightly more
      delayed chronology. Atopy and sex are not risk factors.

PMID- 12220478
TI  - Maternal allergen immunization during pregnancy in a mouse model reduces adult
      allergy-related antibody responses in the offspring.
AB  - BACKGROUND: The immune status and allergen exposure of the mother may influence
      the immune response in the offspring after birth. This relationship may be
      important both for allergen avoidance strategies and, alternatively, for allergy
      prophylaxis by allergen exposure of the mother. OBJECTIVE: The aim of the present
      study was to investigate the effect of allergen immunization of the mother during
      pregnancy and postpartum, in relation to the allergy-related immune response
      (IgE) and the non-allergy-related (IgG2a) response in the offspring. METHODS:
      Pregnant NIH/OlaHsd females were immunized three times during pregnancy and one
      time postpartum with ovalbumin and the adjuvant Al(OH)3, and the offspring's
      ovalbumin-specific IgE, IgG1 and IgG2a responses were measured after challenge
      with the same allergen as young adults. Ovalbumin-specific IgE, IgG1 and IgG2a
      responses were also analysed in offspring of NIH/OlaHsd females immunized once at
      different times during pregnancy: about 3 days into pregnancy, mid-pregnancy (10
      days into pregnancy) and about 4 days before giving birth (17 days into
      pregnancy). RESULTS: Allergen immunization of mother during pregnancy and
      postpartum significantly reduced the IgE response in the progenies, whereas the
      IgG2a response to the same allergen was increased. Allergen immunization of the
      mother 3 days into pregnancy resulted in a significantly lower IgE response in
      offspring compared with the response in offspring of non-immunized mothers and in
      offspring of mothers immunized 17 days into pregnancy. CONCLUSIONS: Maternal
      allergen immunization might favour selection for an allergen-specific Th1
      dependent antibody response in the offspring. Our results indicate that IgE
      suppression is stronger after maternal allergen exposure during early pregnancy
      than after exposure in late pregnancy.

PMID- 12220481
TI  - How should an infected perinephric haematoma be drained in a tetraplegic patient
      with baclofen pump implanted in the abdominal wall? - A case report.
AB  - BACKGROUND: We present a case to illustrate controversies in percutaneous
      drainage of infected, perinephric haematoma in a tetraplegic patient, who had
      implantation of baclofen pump in anterior abdominal wall on the same side as
      perinephric haematoma. CASE PRESENTATION: A 56-year-old male with C-4 tetraplegia
      had undergone implantation of programmable pump in the anterior abdominal wall
      for intrathecal infusion of baclofen to control spasticity. He developed
      perinephric haematoma while he was taking warfarin as prophylactic for deep vein
      thrombosis. Perinephric haematoma became infected with a resistant strain of
      Pseudomonas aeruginosa, and required percutaneous drainage. Positioning this
      patient on his abdomen without anaesthesia, for insertion of a catheter from
      behind, was not a realistic option. Administration of general anaesthesia in this
      patient in the radiology department would have been hazardous. RESULTS AND
      CONCLUSION: Percutaneous drainage was carried out by anterior approach under
      propofol sedation. The site of entry of percutaneous catheter was close to
      cephalic end of baclofen pump. By carrying out drainage from anterior approach,
      and by keeping this catheter for ten weeks, we took a risk of causing infection
      of the baclofen pump site, and baclofen pump with a resistant strain of
      Pseudomonas aeruginosa. The alternative method would have been to anaesthetise
      the patient and position him prone for percutaneous drainage of perinephric
      collection from behind. This would have ensured that the drainage track was far
      away from the baclofen pump with minimal risk of infection of baclofen pump, but
      at the cost of incurring respiratory complications in a tetraplegic subject.

PMID- 12220482
TI  - Effects of chronic inflammatory bowel diseases on left ventricular structure and
      function: a study protocol.
AB  - BACKGROUND: Experimental evidences suggest an increased collagen deposition in
      inflammatory bowel diseases (IBD). In particular, large amounts of collagen type
      I, III and V have been described and correlated to the development of intestinal
      fibrotic lesions. No information has been available until now about the possible
      increased collagen deposition far from the main target organ. In the hypothesis
      that chronic inflammation and increased collagen metabolism are reflected also in
      the systemic circulation, we aimed this study to evaluate the effects on left
      ventricular wall structure by assessing splancnic and systemic collagen
      metabolism (procollagen III assay), deposition (ultrasonic tissue
      characterization), and cardiac function (echocardiography) in patients with
      different long standing history of IBD, before and after surgery. METHODS: Thirty
      patients affected by active IBD, 15 with Crohn and 15 with Ulcerative Colitis,
      submitted to surgery will be enrolled in the study in a double blind fashion.
      They will be studied before the surgical operation and 6, 12 months after
      surgery. A control group of 15 healthy age and gender-matched subjects will also
      be studied. At each interval blood samples will be collected in order to assess
      the collagen metabolism; a transthoracic echocardiogram will be recorded for the
      subsequent determination of cardiac function and collagen deposition. DISCUSSION:
      From this study protocol we expect additional information about the association
      between IBD and cardiovascular disorders; in particular to address the question
      if chronic inflammation, through the altered collagen metabolism, could affect
      left ventricular structure and function in a manner directly related to the
      estimated duration of the disease.

PMID- 12220484
TI  - Polynucleotide kinase: a versatile molecule makes a clean break.

PMID- 12220483
TI  - The functional importance of disease-associated mutation.
AB  - BACKGROUND: For many years, scientists believed that point mutations in genes are
      the genetic switches for somatic and inherited diseases such as cystic fibrosis,
      phenylketonuria and cancer. Some of these mutations likely alter a protein's
      function in a manner that is deleterious, and they should occur in functionally
      important regions of the protein products of genes. Here we show that disease
      associated mutations occur in regions of genes that are conserved, and can
      identify likely disease-causing mutations. RESULTS: To show this, we have
      determined conservation patterns for 6185 non-synonymous and heritable disease
      associated mutations in 231 genes. We define a parameter, the conservation ratio,
      as the ratio of average negative entropy of analyzable positions with reported
      mutations to that of every analyzable position in the gene sequence. We found
      that 84.0% of the 231 genes have conservation ratios less than one. 139 genes had
      eleven or more analyzable mutations and 88.0% of those had conservation ratios
      less than one. CONCLUSIONS: These results indicate that phylogenetic information
      is a powerful tool for the study of disease-associated mutations. Our alignments
      and analysis has been made available as part of the database at
      http://cancer.stanford.edu/mut-paper/. Within this dataset, each position is
      annotated with the analysis, so the most likely disease-causing mutations can be
      identified.

PMID- 12220485
TI  - New light on the integrin switch.

PMID- 12220486
TI  - Another worm in translation.

PMID- 12220487
TI  - A cold look at transcription.

PMID- 12220488
TI  - Betaine-homocysteine methyltransferase: zinc in a distorted barrel.
AB  - Betaine-homocysteine methyl transferase (BHMT) catalyzes the synthesis of
      methionine from betaine and homocysteine (Hcy), utilizing a zinc ion to activate
      Hcy. BHMT is a key liver enzyme that is important for homocysteine homeostasis. X
      ray structures of human BHMT in its oxidized (Zn-free) and reduced (Zn-replete)
      forms, the latter in complex with the bisubstrate analog, S(delta-carboxybutyl)-L
      homocysteine, were determined at resolutions of 2.15 A and 2.05 A. BHMT is a
      (beta/alpha)(8) barrel that is distorted to construct the substrate and metal
      binding sites. The zinc binding sequences G-V/L-N-C and G-G-C-C are at the C
      termini of strands beta6 and beta8. Oxidation to the Cys217-Cys299 disulfide and
      expulsion of Zn are accompanied by local rearrangements. The structures identify
      Hcy binding fingerprints and provide a prototype for the homocysteine S
      methyltransferase family.

PMID- 12220489
TI  - An NMR view of the folding process of a CheY mutant at the residue level.
AB  - The folding of CheY mutant F14N/V83T was studied at 75 residues by NMR.
      Fluorescence, NMR, and sedimentation equilibrium studies at different urea and
      protein concentrations reveal that the urea-induced unfolding of this CheY mutant
      includes an on-pathway molten globule-like intermediate that can associate off
      pathway. The populations of native and denatured forms have been quantified from
      a series of 15N-1H HSQC spectra recorded under increasing concentrations of urea.
      A thermodynamic analysis of these data provides a detailed picture of the
      mutant's unfolding at the residue level: (1) the transition from the native state
      to the molten globule-like intermediate is highly cooperative, and (2) the
      unfolding of this state is sequential and yields another intermediate showing a
      collapsed N-terminal domain and an unfolded C-terminal tail. This state presents
      a striking similarity to the kinetic transition state of the CheY folding
      pathway.

PMID- 12220490
TI  - Crystal structure of the MuSK tyrosine kinase: insights into receptor
      autoregulation.
AB  - Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed selectively
      in skeletal muscle. During neuromuscular synapse formation, agrin released from
      motor neurons stimulates MuSK autophosphorylation in the kinase activation loop
      and in the juxtamembrane region, leading to clustering of acetylcholine
      receptors. We have determined the crystal structure of the cytoplasmic domain of
      unphosphorylated MuSK at 2.05 A resolution. The structure reveals an
      autoinhibited kinase domain in which the activation loop obstructs ATP and
      substrate binding. Steady-state kinetic analysis demonstrates that
      autophosphorylation results in a 200-fold increase in k(cat) and a 10-fold
      decrease in the K(m) for ATP. These studies provide a molecular basis for
      understanding the regulation of MuSK catalytic activity and suggest that an
      additional in vivo component may contribute to regulation via the juxtamembrane
      region.

PMID- 12220491
TI  - C-H...O hydrogen bonds in the nuclear receptor RARgamma--a potential tool for
      drug selectivity.
AB  - Hydrogen bonds between polarized atoms play a crucial role in protein
      interactions and are often used in drug design, which usually neglects the
      potential of C-H...O hydrogen bonds. The 1.4 A resolution crystal structure of
      the ligand binding domain of the retinoic acid receptor RARgamma complexed with
      the retinoid SR11254 reveals several types of C-H...O hydrogen bonds. A striking
      example is the hydroxyl group of the ligand that acts as an H bond donor and
      acceptor, leading to a synergy between classical and C-H...O hydrogen bonds. This
      interaction introduces both specificity and affinity within the hydrophobic
      ligand pocket. The similarity of intraprotein and protein-ligand C-H...O
      interactions suggests that such bonds should be considered in rational drug
      design approaches.

PMID- 12220492
TI  - Trichromatic concept optimizes MAD experiments in synchrotron X-ray
      crystallography.
AB  - The trichromatic concept is a new synchrotron beamline design that optimizes MAD
      experiments by reducing systematic experimental errors with three-colored and
      coaxial synchrotron X-ray beams produced by a tandem vertical undulator and
      trichromator. The concept enables rapid and flexible switching of three defined
      wavelengths, and extends the flexibility of experimental design for MAD data
      collection. Thus, we can collect MAD data taking into account time series effects
      such as radiation damage. The data based on the trichromatic concept gave a
      better quality electron density map than data collected by conventional methods.
      It was also revealed that multicolor diffraction using dichromatic or
      trichromatic X-ray beams is effective in rapid MAD data collection.

PMID- 12220493
TI  - E. coli dihydroorotate dehydrogenase reveals structural and functional
      distinctions between different classes of dihydroorotate dehydrogenases.
AB  - The flavoenzymes dihydroorotate dehydrogenases (DHODs) catalyze the fourth and
      only redox step in the de novo biosynthesis of UMP. Enzymes belonging to class 2,
      according to their amino acid sequence, are characterized by having a serine
      residue as the catalytic base and a longer N terminus. The structure of class 2
      E. coli DHOD, determined by MAD phasing, showed that the N-terminal extension
      forms a separate domain. The catalytic serine residue has an environment
      differing from the equivalent cysteine in class 1 DHODs. Significant differences
      between the two classes of DHODs were identified by comparison of the E. coli
      DHOD with the other known DHOD structures, and differences with the class 2 human
      DHOD explain the variation in their inhibitors.

PMID- 12220494
TI  - Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds
      fatty acids.
AB  - The 2.7 A X-ray crystal structure of the HNF4gamma ligand binding domain (LBD)
      revealed the presence of a fatty acid within the pocket, with the AF2 helix in a
      conformation characteristic of a transcriptionally active nuclear receptor. GC/MS
      and NMR analysis of chloroform/methanol extracts from purified HNF4alpha and
      HNF4gamma LBDs identified mixtures of saturated and cis-monounsaturated C14-18
      fatty acids. The purified HNF4 LBDs interacted with nuclear receptor
      coactivators, and both HNF4 subtypes show high constitutive activity in transient
      transfection assays, which was reduced by mutations designed to interfere with
      fatty acid binding. The endogenous fatty acids did not readily exchange with
      radiolabeled palmitic acid, and all attempts to displace them without denaturing
      the protein failed. Our results suggest that the HNF4s may be transcription
      factors that are constitutively bound to fatty acids.

PMID- 12220495
TI  - Comparison of in vivo selection and rational design of heterodimeric coiled
      coils.
AB  - To investigate how electrostatic interactions restrict the associations of coiled
      coils, we improved a heterodimeric coiled coil (WinZip-A1B1) by in vivo selection
      and, alternatively, by rational design. Selection from libraries encoding
      variable edge (g and e) residues enriched g/e' ion pairs, but the optimum
      selected heterodimers unexpectedly retained two predicted repulsive g/e' pairs.
      The best genetically selected heterodimer displayed similar thermodynamic
      stability and specificity as a rationally designed dimer with predicted ion pairs
      at all edge positions. This rationally designed pair, however, was less effective
      than the best genetically selected pair in mediating dimerization in vivo. Thus,
      the effects of predicted charge pairs depend on sequence context, and
      complementary charges at the edge positions rationalize only a fraction of the
      sequences that form stable, specific coiled coils.

PMID- 12220496
TI  - Structure of a tRNA repair enzyme and molecular biology workhorse: T4
      polynucleotide kinase.
AB  - T4 phage polynucleotide kinase (PNK) was identified over 35 years ago and has
      become a staple reagent for molecular biologists. The enzyme displays 5'-hydroxyl
      kinase, 3'-phosphatase, and 2',3'-cyclic phosphodiesterase activities against a
      wide range of substrates. These activities modify the ends of nicked tRNA
      generated by a bacterial response to infection and facilitate repair by T4 RNA
      ligase. DNA repair enzymes that share conserved motifs with PNK have been
      identified in eukaryotes. PNK contains two functionally distinct structural
      domains and forms a homotetramer. The C-terminal phosphatase domain is homologous
      to the L-2-haloacid dehalogenase family and the N-terminal kinase domain is
      homologous to adenylate kinase. The active sites have been characterized through
      structural homology analyses and visualization of bound substrate.

PMID- 12220497
TI  - Gene sequence and the 1.8 A crystal structure of the tungsten-containing formate
      dehydrogenase from Desulfovibrio gigas.
AB  - Desulfovibrio gigas formate dehydrogenase is the first representative of a
      tungsten-containing enzyme from a mesophile that has been structurally
      characterized. It is a heterodimer of 110 and 24 kDa subunits. The large subunit,
      homologous to E. coli FDH-H and to D. desulfuricans nitrate reductase, harbors
      the W site and one [4Fe-4S] center. No small subunit ortholog containing three
      [4Fe-4S] clusters has been reported. The structural homology with E. coli FDH-H
      shows that the essential residues (SeCys158, His159, and Arg407) at the active
      site are conserved. The active site is accessible via a positively charged
      tunnel, while product release may be facilitated, for H(+) by buried waters and
      protonable amino acids and for CO(2) through a hydrophobic channel.

PMID- 12220498
TI  - Translocation mechanism of long sugar chains across the maltoporin membrane
      channel.
AB  - Maltoporin allows permeation of long maltodextrin chains. It tightly binds the
      amphiphilic sugar, offering both hydrophobic interactions with a helical lane of
      aromatic residues and H bonds with ionic side chains. The minimum-energy path of
      maltohexaose translocation is obtained by the conjugate peak refinement method,
      which optimizes a continuous string of conformers without applying constraints.
      This reveals that the protein is passive while the sugar glides screw-like along
      the aromatic lane. Near instant switching of sugar hydroxyl H bond partners
      results in two small energy barriers (of approximately 4 kcal/mol each) during
      register shift by one glucosyl unit, in agreement with a kinetic analysis of
      experimental dissociation rates for varying sugar chain lengths. Thus, maltoporin
      functions like an efficient translocation "enzyme," and the slow rate of the
      register shift (approximately 1/ms) is due to high collisional friction.

PMID- 12220499
TI  - Gene targeting by homologous recombination: a powerful addition to the genetic
      arsenal for Drosophila geneticists.
AB  - A series of recent publications have firmly established the notion that
      Drosophila researchers now have a general method to subject genes for targeted
      modification by homologous recombination (HR) [Science 288 (2000) 2013; Genetics
      157 (3) (2001) 1307; Genes Dev. 16 (12) (2002) 1568; Genetics 161 (2002) 1125
      1136]. This method allows one to knockout essentially any gene starting with the
      DNA sequence of the gene. It has greatly enhanced studies of gene function as
      demonstrated by over 20 years of gene targeting practice in yeast and mouse.
      Here, I discuss the basic targeting methodology for eukaryotic organisms. I
      compare the Drosophila method with the traditional targeting scheme in yeast and
      mouse mainly to show that the targeting mechanism as well as many aspects of the
      experimental design remain unchanged, and that the Drosophila scheme differs only
      in the way in which the donor molecule for targeting is generated. I propose that
      the Drosophila method can be readily adapted in other organisms without
      culturable stem cells, since the mechanism for in vivo donor generation in
      Drosophila is likely to be functional in a variety of different organisms.

PMID- 12220500
TI  - A conversation with Thomas D. Pollard. Interview by K. Noelle Gracy.

PMID- 12220501
TI  - Functional properties of Kch, a prokaryotic homologue of eukaryotic potassium
      channels.
AB  - To test the hypothesis that the Kch gene of Escherichia coli encodes a potassium
      channel, we have transformed E. coli with an expression vector containing the Kch
      sequence and observed the effect of over-expression of Kch on E. coli. We found
      that: (i) over-expression of Kch is toxic to E. coli, but the toxicity could be
      prevented by supplementing the growth medium with K(+), Rb(+), and NH(4)(+), but
      not Na(+), consistent with the properties of a potassium selective pore; (ii)
      Cs(+), a blocker of potassium channels, rescues the growth of Kch over-expressing
      cells; and (iii) when the putative pore-forming region of Kch, containing the
      signature sequence, was replaced with the corresponding region of the eukaryotic
      Shaker potassium channel, and the resultant construct expressed in E. coli, the
      cells became critically dependent on K(+) supply for survival. These data are
      consistent with the proposed function of Kch, i.e., K(+) conduction.

PMID- 12220502
TI  - A new ERK2 binding protein, Naf1, attenuates the EGF/ERK2 nuclear signaling.
AB  - Extracellular signal regulated kinase1/2 (ERK1/2), an important factor in signal
      transduction, controls cell growth, differentiation, and death. To elucidate the
      details of the mechanism of ERK1/2 signaling in human cells, we isolated Nef
      associated factor 1 alpha (Naf1 alpha) by a yeast two-hybrid system, which bound
      to human ERK2. The binding was confirmed by a pull-down assay in vitro and
      immunoprecipitation in vivo. Upon EGF treatment, Naf1 alpha was phosphorylated by
      the EGF/MEK/ERK2 signal transduction pathway. To identify the role of Naf1 alpha
      in the ERK2 signaling, Naf1 alpha-expressing Saos-2 cells were analyzed for ERK2
      nuclear translocation and activation of its downstream target. Overexpression of
      Naf1 alpha suppressed ERK2 entering into the nucleus and inhibited the ERK2
      dependent Elk1-driven luciferase transcription, suggesting Naf1 alpha to be an
      attenuator of activated ERK2 signaling.

PMID- 12220503
TI  - The identification of thymidylate synthase peptide domains located in the
      interface region that bind thymidylate synthase mRNA.
AB  - Thymidylate synthase (TS) is a critical chemotherapeutic target and intracellular
      levels of TS are an important determinant of sensitivity to TS inhibitors.
      Translational autoregulation represents one cellular mechanism for controlling
      the level of expression of TS. This mechanism involves the binding of TS protein
      to its own messenger RNA (mRNA), thus, repressing translational efficiency. The
      presence of excess substrate or inhibitors of TS leads to derepression of protein
      binding to mRNA, resulting in increased translational efficiency and ultimately
      increased levels of TS protein. TS protein has been shown to bind to two distinct
      areas on its mRNA. The goal of the present work is to define the TS domains
      responsible for this interaction. Using a separate series of overlapping 17-mer
      peptides spanning the length of both the human and Escherichia coli TS sequences,
      we have identified six potential domains located in the interface region of the
      TS protein that bind TS mRNA. The identified domains that bind TS mRNA include
      three concordant regions in both the human and E. coli peptide series. Five of
      the six binding peptides contain at least one invariant arginine residue, which
      has been shown to be critical in other well-defined protein-RNA interactions.
      These data suggest that the identified highly conserved protein domains, which
      occur at the homodimeric interface of TS, represent potential participating sites
      for binding of TS protein to its mRNA.

PMID- 12220504
TI  - Interaction of plexin-B1 with PDZ domain-containing Rho guanine nucleotide
      exchange factors.
AB  - The Rho family GTPase has been implicated in plexin-B1, a receptor for Semaphorin
      4D (Sema4D), mediating signal transduction. Rho may also play a function in this
      signaling pathway as well as Rac, but the mechanisms for Rho regulation are
      poorly understood. In this study, we have identified two kinds of PDZ domain
      containing Rho-specific guanine nucleotide exchange factors (RhoGEFs) as proteins
      interacting with plexin-B1 cytoplasmic domain. These PDZ domain-containing
      RhoGEFs showed significant homology to human KIAA0380 (PDZ-RhoGEF) and LARG
      (KIAA0382), respectively. Both KIAA0380 and LARG could bind plexin-B1 and a
      deletion mutant analysis of plexin-B1, KIAA0380 and LARG revealed that KIAA0380
      and LARG bound plexin-B1 cytoplasmic tail through their PDZ domains. The tissue
      distribution analysis indicated that plexin-B1 was co-localized with KIAA0380 and
      LARG in various tissues. Immunocytochemical analysis showed that LARG was
      recruited to plasma membrane by plexin-B1. These results suggest that PDZ domain
      containing RhoGEFs play a role in Sema4D-plexin-B1 mediating signal transduction.

PMID- 12220505
TI  - Inhibition of MEPE cleavage by Phex.
AB  - X-linked hypophosphatemia (XLH) and the Hyp-mouse disease homolog are caused by
      inactivating mutations of Phex which results in the local accumulation of an
      unknown autocrine/paracrine factor in bone that inhibits mineralization of
      extracellular matrix. In these studies, we evaluated whether the matrix
      phosphoglycoprotein MEPE, which is increased in calvaria from Hyp mice, is a
      substrate for Phex. Using recombinant full-length Phex (rPhexWT) produced in Sf9
      cells, we failed to observe Phex-dependent hydrolysis of recombinant human MEPE
      (rMEPE). Rather, we found that rPhex-WT inhibited cleavage of rMEPE by endogenous
      cathepsin-like enzyme activity present in Sf9 membrane. Sf9 membranes as well as
      purified cathepsin B cleaved MEPE into two major fragments of approximately 50
      and approximately 42kDa. rPhexWT protein in Sf9 membrane fractions, co-incubation
      of rPhexWT and cathepsin B, and pre-treatment of Sf9 membranes with leupeptin
      prevented the hydrolysis of MEPE in vitro. The C-terminal domain of Phex was
      required for inhibition of MEPE cleavage, since the C-terminal deletion mutant
      rPhex (1-433) [rPhex3(')M] failed to inhibit Sf9-dependent metabolism of MEPE.
      Phex-dependent inhibition of MEPE degradation, however, did not require Phex
      enzymatic activity, since EDTA, an inhibitor of rPhex, failed to block rPhexWT
      inhibition of MEPE cleavage by Sf9 membranes. Since we were unable to identify
      interactions of Phex with MEPE or actions of Phex to metabolize cathepsin B, Phex
      may be acting to interfere with the actions of other enzymes that degrade
      extracellular matrix proteins. Although the molecular mechanism and biological
      relevance of non-enzymatic actions of Phex need to be established, these findings
      indicate that MEPE may be involved in the pathogenesis defective mineralization
      due to Phex deficiency in XLH and the Hyp-mouse.

PMID- 12220506
TI  - Fluid flow induces COX-2 expression in MC3T3-E1 osteoblasts via a PKA signaling
      pathway.
AB  - Mechanical loading of bone generates fluid flow within the mineralized matrix
      which can exert fluid shear stress (FSS) at cell membranes. FSS induces new
      transcription of cyclooxygenase-2 (COX-2) in MC3T3-E1 osteoblasts, with peak
      effects at 4-5h. Using MC3T3-E1 cells stably transfected with the COX-2 promoter
      fused to a luciferase reporter, we examined involvement of the protein kinase A
      (PKA) and protein kinase C (PKC) signaling pathways in the peak COX-2 mRNA and
      luciferase responses to FSS (10dyn/cm(2)). Neither inhibition nor down-regulation
      of the PKC pathway affected the FSS stimulation of COX-2 mRNA or luciferase
      activity. In contrast, inhibitors of the PKA pathway, used at doses which
      inhibited forskolin-stimulated luciferase activity by 70-80%, reduced FSS
      stimulated COX-2 mRNA expression and luciferase activity by 50-80%. Hence, peak
      FSS induction of COX-2 expression in MC3T3-E1 osteoblastic cells is largely
      dependent on the PKA signaling pathway.

PMID- 12220507
TI  - Identification and characterization of murine IRAK-2.
AB  - Interleukin-1 receptor-associated kinases (IRAKs) are pivotal signaling elements
      of the Toll/IL-1 receptor (TIL) family, which play a role in innate immune
      responses by coordinating host defence mechanisms. Presently four different forms
      of human IRAK molecules are cloned (hu-IRAK-1, hu-IRAK-2, hu-IRAK-M, and hu-IRAK
      4). In the murine system, only three genes have been identified so far, mouse
      Pelle-Like Kinase (mPLK), which corresponds to human IRAK-1, mu-IRAK-M, and mu
      IRAK-4. Here we report the molecular cloning and characterization of murine IRAK
      2 (mu-IRAK-2), a mouse homolog to human IRAK-2 (hu-IRAK-2). Murine and human IRAK
      2 molecules show 67% sequence identity, they are ubiquitiously expressed, and
      both practically lack autophoshorylation kinase activity. The murine molecule
      reveals two remarkable differences to its human counterpart: it shows a C
      terminal extension and it has no stimulatory effect on IL-1 induced NF-kappa B
      activation when compared to hu-IRAK-2, suggesting subtle functional differences
      in signaling by IRAK-2 in human and mouse cells.

PMID- 12220508
TI  - Expression of survivin during liver regeneration.
AB  - Survivin functions to suppress cell death and regulate cell division, and is
      observed uniquely in tumor cells and developmental cells. However, the expression
      and regulation of survivin in non-transformed cells are not well elucidated.
      Therefore, we investigated the expression of survivin in a murine liver
      regeneration model after partial hepatectomy and intraperitoneal carbon
      tetrachloride (CCl(4)) injection. We found that the expression of survivin
      transcript and protein were markedly elevated with the onset of DNA synthesis and
      remained elevated during G2 and M phases during liver regeneration. In a normal
      mouse liver cell line, over-expression of survivin resulted in a decrease in the
      G0/G1 phase and an increase in the S and G2/M phases, resulting in Rb
      phosphorylation. These findings suggest that survivin is dramatically expressed
      in a cell cycle-dependent manner during liver regeneration and provide a new
      insight into the regulation of cell proliferation and differentiation.

PMID- 12220509
TI  - Expression of P450 enzymes in rat whole skin and cultured epidermal
      keratinocytes.
AB  - The complement and level of expression of P450 enzymes in male Fischer F344 rat
      whole skin and cultured keratinocytes were investigated using a panel of mono
      specific antibodies. In whole skin microsomal fraction, immunoreactive bands
      corresponding to CYP2B12, CYP2C13, CYP2D1, CYP2D4, CYP2E1, CYP3A1, and CYP3A2
      were detected whereas CYP1A1, CYP1A2, and CYP2C12 were absent. Skin levels were
      all between 0.1% and 4.7% of those found in liver, except for CYP2D4, which was
      not detected in liver. Keratinocytes were isolated from rat skin, cultured for up
      to 42 days, and changes in the levels of CYP3A1, CYP3A2, and CYP2E1 determined.
      Levels were low in isolated keratinocytes, but they increased markedly in
      culture, reaching a maximum at 10-14 days, where they were similar to those found
      in fresh skin. This suggests that primary keratinocytes grown in culture for 10
      14 days may provide a useful experimental model to study P450-catalysed
      metabolism of xenobiotics in skin.

PMID- 12220510
TI  - Aminoglycoside antibiotics induce pH-sensitive activation of the calcium-sensing
      receptor.
AB  - The aminoglycoside antibiotic (AGA) neomycin is a known agonist of the
      extracellular calcium-sensing receptor (CaR). To test whether other AGA drugs
      stimulate the CaR, we studied the relative effects of four AGAs on intracellular
      Ca(2+) concentration ([Ca(2+)](i)) using CaR-transfected human embryonic kidney
      (HEK)-293 cells. Gentamicin, tobramycin, and neomycin evoked dose-dependent
      increases in [Ca(2+)](i) with EC(50) values of 258, 177, and 43 microM,
      respectively, in CaR-transfected, but not in non-transfected cells. Kanamycin was
      ineffective at doses <1mM. Thus, AGAs stimulate the CaR with a rank order of
      potency that correlates positively with the number of their attached amino
      groups. The CaR is expressed on the apical surface of renal proximal tubule
      cells, which is also the site of AGA endocytosis and nephrotoxicity. In the
      current study, reducing extracellular pH from 7.4 to 6.9, to mimic the luminal pH
      of the proximal tubule, enhanced the sensitivity of the CaR to tobramycin,
      suggesting that the AGAs may be more potent CaR agonists in the proximal tubule
      than elsewhere. This pH effect was not observed when stimulating CaR with the non
      ionizable agonist, Gd(3+), suggesting that the enhanced AGA effect is due to
      increased ionization of the drug. Thus, we show that a number of AGA drugs are
      capable of CaR activation and that their potency most likely relates to the
      number of their amino side chains and to their pH-dependent charge
      characteristics. The contribution of CaR activation to the
      pharmacological/toxicological effects of these AGAs remains to be determined.

PMID- 12220511
TI  - DUG is a novel homologue of translation initiation factor 4G that binds eIF4A.
AB  - To elucidate the molecular mechanisms of cell death, we have cloned a new gene,
      designated death-upregulated gene (DUG), from rat insulinoma cells. DUG is
      constitutively expressed at very low levels in normal cells but is dramatically
      upregulated in apoptotic cells following serum/glucose starvation or death
      receptor ligation by Fas ligand. The DUG mRNA is present in two splicing forms: a
      long form that encodes a protein of 469 amino acids and a short form that gives
      rise to a polypeptide of 432 amino acids. The predicted DUG protein sequence
      contains two putative nuclear localization signals and multiple phosphorylation
      sites for protein kinases and two conserved MA3 domains. Importantly, DUG is
      homologous to eukaryotic translation initiation factor (eIF) 4G and binds to
      eIF4A presumably through MA3 domains. Upon transfection, DUG inhibits both
      intrinsic and extrinsic pathways of apoptosis. Thus, DUG is a novel homologue of
      eIF4G that regulates apoptosis.

PMID- 12220512
TI  - Potent CpG oligonucleotides containing phosphodiester linkages: in vitro and in
      vivo immunostimulatory properties.
AB  - Bacterial and synthetic DNAs, containing CpG dinucleotides in specific sequence
      contexts, activate the vertebrate immune system. Unlike phosphorothioate (PS) CpG
      DNAs, phosphodiester (PO) CpG DNAs require either palindromic sequences and/or
      poly(dG) sequences at the 3(')-end for activity. Here, we report 'PO-immunomers'
      having two PO-CpG DNA molecules joined through their 3(')-ends. These PO
      imunomers permitted us, for the first time, to assess immunostimulatory
      properties of PO-CpG DNAs in vitro and in vivo without the need for palindromic
      and/or poly(dG) sequences. In medium containing 10% fetal bovine serum, PO
      immunomers were more resistant than PO-CpG DNAs to nucleases. Compared to PS-CpG
      DNA in BALB/c and C3H/HeJ mice spleen cell culture assays, PO-immunomers showed
      increased IL-12 secretion and minimal amounts of IL-6 secretion. PO-immunomers
      activated NF-kappa B and induced cytokine secretion in J774 cell cultures. In
      addition, PO-immunomers showed antitumor activity in nude mice bearing human
      breast (MCF-7) and prostate (DU145) cancer xenografts.

PMID- 12220513
TI  - Correlation between cellular localization of TEL/AML1 fusion protein and
      repression of AML1-mediated transactivation of CR1 gene.
AB  - Human chromosome translocation t(12;21)(p12;q22) is the most frequent chromosome
      rearrangement in childhood B-lineage acute lymphoblastic leukemia (ALL), and
      produces the TEL/AML1 fusion protein. The chimeric protein, TEL/AML1 contains the
      first 336 amino acids of TEL that is linked to residues 21-480 of AML1 and the
      fusion protein is generally known as a transcription repressor to the various
      target genes. Furthermore, TEL/AML1 has been shown to interfere with AML1
      mediated transactivation on the CR1 gene. To understand the mechanism of the
      TEL/AML1-mediated repression, we used transient-transfection assay and
      immunofluorescence to monitor subcellular localization of TEL/AML1. Here, we show
      that TEL/AML1 is localized in the cytoplasm and the transcriptional activities of
      CR1 promoter are affected by the subcellular localization of TEL/AML1 fusion
      protein.

PMID- 12220514
TI  - cDNA cloning and characterization of Drb1, a new member of RRM-type neural RNA
      binding protein.
AB  - Neural RNA recognition motif (RRM)-type RNA-binding proteins play essential roles
      in neural development. To search for a new member of neural RRM-type RNA-binding
      protein, we screened rat cerebral expression library with polyclonal antibody
      against consensus RRM sequences. We have cloned and characterized a rat cDNA that
      belongs to RRM-type RNA-binding protein family, which we designate as drb1.
      Orthologs of drb1 exist in human and mouse. The predicted amino acid sequence
      reveals an open reading frame of 476 residues with a corresponding molecular mass
      of 53kDa and consists of four RNA-binding domains. drb1 gene is specifically
      expressed in fetal (E12, E16) rat brain and gradually reduced during development.
      In situ hybridization demonstrated neuron-specific signals in fetal rat brain.
      RNA-binding assay indicated that human Drb1 protein possesses binding preference
      on poly(C)RNA. These results indicate that Drb1 is a new member of neural RNA
      binding proteins, which expresses under spatiotemporal control.

PMID- 12220515
TI  - Mixed lineage kinase ZAK utilizing MKK7 and not MKK4 to activate the c-Jun N
      terminal kinase and playing a role in the cell arrest.
AB  - The leucine-zipper (LZ) and sterile-alpha motif (SAM) kinase (ZAK) belongs to the
      MAP kinase kinase kinase (MAP3K) when upon over-expression in mammalian cells
      activates the JNK/SAPK pathway. The mechanisms by which ZAK activity is regulated
      are not well understood. Co-expression of dominant-negative MKK7 but not MKK4 and
      ZAK significantly attenuates JNK/SAPK activation. This result suggests that ZAK
      activates JNK/SAPK mediated by downstream target, MKK7. Expression of ZAK but not
      kinase-dead ZAK in 10T1/2 cells results in the disruption of actin stress fibers
      and morphological changes. Therefore, ZAK activity may be involved in actin
      organization regulation. Expression of wild-type ZAK increases the cell
      population in the G(2)/M phase of the cell cycle, which may indicate G(2) arrest.
      Western blot analysis shows that the decreased cyclin E level correlated strongly
      with the low proliferative capacity of ZAK-expressed cells.

PMID- 12220516
TI  - Dual abnormal effects of mutant MITF encoded by Mi(wh) allele on mouse mast
      cells: decreased but recognizable transactivation and inhibition of
      transactivation.
AB  - MITF is a basic helix-loop-helix leucine zipper-type transcription factor and is
      important for development of mast cells. MITF encoded by Mi(wh) allele (Mi(wh)
      MITF) was mutated at a single amino acid of basic domain, and possessed a
      deficient but apparent DNA-binding ability. Here, we characterized the unique
      effects of Mi(wh)-MITF on the expression of mast cell-related genes. The
      expression level of mouse mast cell protease (mMCP)-4, -5, and -6 genes in
      Mi(wh)/Mi(wh) cultured mast cells (CMCs) was intermediate between levels of
      normal (+/+) CMCs and tg/tg CMCs, which did not express any MITFs. Mi(wh)-MITF
      appeared to show the positive transactivation effect through the remaining DNA
      binding ability. On the other hand, the expression level of tryptophan
      hydroxylase gene was lower in Mi(wh)/Mi(wh) CMCs than in tg/tg CMCs, suggesting
      the inhibitory effect of Mi(wh)-MITF on the transactivation. Mi(wh)-MITF
      possessed dual abnormal effects on transactivation of mast cell-related genes.

PMID- 12220517
TI  - The role of Sp1 in BMP2-up-regulated Erk2 gene expression.
AB  - Extracellular signal-regulated kinase (Erk) is an important component in many
      cellular processes, including cell differentiation and proliferation. We
      previously showed that Erk is involved in BMP2-induced osteoblastic
      differentiation in mesenchymal progenitor cells and Erk protein level is up
      regulated under BMP2 inducement. In this study, the molecular mechanism which
      mediates the regulation of Erk2 gene expression by BMP2 was investigated.
      Northern blot analysis showed that increased Erk2 protein level under BMP2
      inducement comes from BMP2-up-regulated Erk2 mRNA expression. Transient
      transfection of C3H10T1/2 cells with a series of constructs of mouse Erk2
      promoter demonstrated that a sequence residing between nucleotides -148 and -42
      of Erk2 promoter is one of the BMP2-responsive elements. Electrophoresis mobility
      shift assays indicated that BMP2 treatment on C3H10T1/2 cells increases the
      binding of cell nuclear extracts to the -148/-42 fragment, and the BMP2-enhanced
      binding bands are Sp1 transcription factors. A series of competitive gel shift
      assays and the supershift assays by mapping oligos S1-S5 on -148/-42 identified
      that S1 and S5 contain Sp1 binding sites, which are located, respectively, in 
      147/-139 and -51/-46. Transfection studies showed that the addition of the Sp1
      binding inhibitor mithramycin or mutation of the Sp1 site residing at -147/-139
      abolishes the up-regulation of Erk2 promoter activity induced by BMP2. All these
      results indicate that Sp1-mediated transcription is one of the mechanisms, which
      is responsible for BMP2-induced up-regulation of Erk2 expression.

PMID- 12220518
TI  - Hypermethylation and histone deacetylation lead to silencing of the maspin gene
      in human breast cancer.
AB  - Maspin is a member of the serine protease inhibitor family with tumor suppressing
      activity in breast cancer. Maspin expression was found in normal breast
      epithelial cells, but was frequently decreased in breast cancer cells and lost in
      metastatic cells. In this study, we examined the regulatory mechanism of maspin
      expression and described the re-activation of maspin expression in a series of
      maspin-negative breast cancer cell lines. All of the 6 maspin-negative breast
      cancer cells showed induction of maspin promoter activity in a promoter reporter
      assay. In addition, the treatment of 5-aza-2(') deoxycytidine, trichostatin A or
      a combination of both led to the re-expression of maspin in a series of maspin
      negative breast cancer cell lines. These findings indicate that DNA methylation
      and/or histone deacetylation are/is partially responsible for the silencing of
      maspin gene expression in breast cancer cells. The re-expression of maspin by
      pharmacological intervention potentially offers a promising new target as a
      therapeutic option in breast cancer.

PMID- 12220519
TI  - Heat-shock protein 90 complexes in resting and thrombin-activated platelets.
AB  - Heat-shock protein 90 (hsp90) is a chaperone important for the function of many
      signaling proteins. In this study, we show that hsp90 exists in resting platelets
      as a complex with the heat-shock cognate protein 70 (hsc70), the alpha- and beta
      subunits of protein kinase CK2, and other unidentified phosphoproteins. Platelet
      activation by thrombin caused the rapid dissociation of hsc70 and CK2alpha from
      the hsp90 complex, the ex vivo phosphorylation of many protein components, and
      the stimulation of protein kinase(s) associated with the hsp90 complex. These
      results suggest that the hsp90 complex, with its associated protein kinase(s),
      which may include CK2, and their substrates, is involved in thrombin-induced
      platelet activation.

PMID- 12220521
TI  - The structure of an endomorphin analogue incorporating 1-aminocyclohexane-1
      carboxlylic acid for proline is similar to the beta-turn of Leu-enkephalin.
AB  - Endomorphin (EM2, Tyr-Pro-Phe-Phe-NH(2)) can assume various conformations related
      to cis/trans-rotamers of the amide linkage of Tyr-Pro. To control isomerization,
      restricted or flexible components have been introduced at the Pro position. We
      focused on [Chx(2)]EM2, an EM2 analogue substituting 1-aminocyclohexane-1
      carboxlylic acid (Chx) for Pro. X-ray diffraction analysis revealed that
      [Chx(2)]EM2 is folded into the trans-form of Tyr-Chx. The manner of folding
      resembled that seen in D-TIPP, an EM analogue incorporating
      tetrahydroisoquinoline carboxylic acid, as well as the beta-turn of Leu
      enkephalin. Selectivity for the opioid mu-receptor was fairly well conserved by
      [Chx(2)]EM, suggesting that the folded form is important for mu-selectivity.

PMID- 12220520
TI  - Insulin suppression of VLDL apo B secretion is not mediated by the LDL receptor.
AB  - Insulin inhibits hepatic very low density lipoprotein (VLDL) apo B secretion in
      rats. Current studies test whether the insulin effect is LDL receptor-mediated by
      examining the effect of insulin on VLDL apo B secretion in hepatocytes derived
      from Ldlr-/- and control mice. Primary hepatocytes were incubated overnight with
      media containing 14C-leucine and either 0.1nM (basal) or 200nM insulin.
      Afterwards, secreted VLDL B100 and B48 were quantitated. Insulin reduced 14C
      labeled B100 and B48 comparably in control and Ldlr-/- hepatocytes with a 62+/
      12% vs. 59+/-12% decrease in B100, and a 56+/-11% vs. 61+/-9% decrease in B48.
      Results indicate: (1) mouse hepatocytes respond to insulin by reducing VLDL apo B
      output; (2) both VLDL B100 and B48 secretion are suppressed; and (3) insulin
      inhibition of VLDL apo B secretion is retained in Ldlr-/- hepatocytes.

PMID- 12220522
TI  - A flat squared conformation of an ascidiacyclamide derivative caused by chiral
      modification of an oxazoline residue.
AB  - We designed a deoxazoline-ascidiacyclamide (dASC), cyclo(-L-Ile-L-allo-Thr-D-Val
      thiazole-)(2), diastereomer having 10S, 11R, 37R, and 38S configurations
      ([SR,RS]dASC) and a corresponding product having 10S, 11S, 37R, and 38R
      configurations ([SS,RR]ASC) with the aim of understanding better the relationship
      between conformational behaviour and chirality. X-ray diffraction analysis
      revealed that [SR,RS]dASC is folded in a manner similar to other dASC analogues.
      By contrast, [SS,RR]ASC is a novel, flat conformer that is larger than the major
      square and folded ASC conformers and contains a cavity created by the flat
      peptide ring. In addition, [SS,RR]ASC retains approximately 60% of the
      cytotoxicity of the parent molecule.

PMID- 12220523
TI  - HIPK2 associates with RanBPM.
AB  - Using the yeast two-hybrid system, we have identified the Ran-binding protein
      (RanBPM) as an interaction partner of homeodomain-interacting protein kinase 2
      (HIPK2). RanBPM has been described as a centrosomal protein through which Ran
      regulates the centrosomal function. HIPK2 is mainly a nuclear protein, which
      among other functions represses transcription mediated by homeodomain containing
      transcription factors. Here, we show that overexpressed wildtype HIPK2 and a
      kinase defective mutant of HIPK2 directly interact with RanBPM in the nucleus of
      mammalian cells. Overexpressed wildtype RanBPM and a kinase defective mutant of
      HIPK2 co-localise with HIPK2 in defined nuclear structures. A carboxy- and an
      amino-terminal deletion of HIPK2 do not seem to be able to bind to RanBPM.

PMID- 12220524
TI  - Phe(475) and Glu(446) but not Ser(445) participate in ATP-binding to the alpha
      subunit of Na(+)/K(+)-ATPase.
AB  - The ATP-binding site of Na(+)/K(+)-ATPase is localized on the large cytoplasmic
      loop of the alpha-subunit between transmembrane helices H(4) and H(5). Site
      directed mutagenesis was performed to identify residues involved in ATP binding.
      On the basis of our recently developed model of this loop, Ser(445), Glu(446),
      and Phe(475) were proposed to be close to the binding pocket. Replacement of
      Phe(475) with Trp and Glu(446) with Gln profoundly reduced the binding of ATP,
      whereas the substitution of Ser(445) with Ala did not affect ATP binding.
      Fluorescence measurements of the fluorescent analog TNP-ATP, however, indicated
      that Ser(445) is close to the binding site, although it does not participate in
      binding.

PMID- 12220526
TI  - Immunoproteasome expression in a nonimmune tissue, the ocular lens.
AB  - Interferon gamma (IFN gamma) induces the expression of three catalytic subunits
      of the 20S proteasome that can replace their constitutive homologues to form the
      "immunoproteasome," named to reflect its antigen presentation function. However,
      immunoproteasome levels and their modulation in nonimmune tissues remain unknown.
      A disrupted lens differentiation program observed in transgenic mice that
      constitutively express IFN gamma in the immune-privileged lens tissue suggests a
      role for this cytokine in differentiation. We have developed a competitive RT-PCR
      assay that demonstrates substantially increased levels of immuno subunits and
      unchanged levels of constitutive subunits in transgenic compared to wild-type
      lenses. Similar results were observed with IFN gamma treated alpha TN4-1 lens
      epithelial cells. A comparison of these subunits in different immune and
      nonimmune mouse tissues revealed unique expression patterns. The presence of
      immuno subunits in nonimmune tissues such as lens suggests that the
      immunoproteasome may also have nonimmune functions, such as that in lens
      differentiation.

PMID- 12220527
TI  - Protein dynamics: imidazole and 2-mercaptoethanol binding to the Rhodobacter
      capsulatus cytochrome c(2) mutant, glycine 95 proline.
AB  - The Class I c-type cytochromes can bind exogenous ligands in the oxidized state,
      with the kinetics of ligand binding providing information on naturally occurring
      intramolecular dynamics. Typically, nitrogenous bases are used as ligands;
      however, it is less well known that 2-mercaptoethanol (BME), a commonly used
      cytochrome reducing agent, can form a complex with the heme. To better understand
      the cytochrome-mercaptan interaction, we have investigated the kinetics of
      binding of BME to wild type and mutants of Rhodobacter capsulatus cytochrome c(2)
      and to horse cytochrome c. Complex formation with the G95P mutant is apparent
      from the formation of a green color and a shift in the Soret peak to 418 nm from
      410 nm upon addition of BME. Unlike horse cytochrome c and wild-type R.
      capsulatus cytochrome c(2), G95P permits the kinetics of formation of the BME
      G95P complex to be measured since complex formation and reduction kinetics can be
      resolved. The affinity constant for the binding of BME to mutant G95P was strong
      ( approximately 1.5 x 10(5)M(-1)) and the kinetics of formation of the BME-G95P
      complex were found to undergo a change in rate-limiting step consistent with a
      concentration-independent protein rearrangement (68s(-1)) followed by second
      order binding of BME ( approximately approximately 1.3 x 10(5)M(-1)s(-1)). The
      most remarkable characteristic of mutant G95P is the relatively large amount of
      high-spin species in equilibrium with the low- spin form, which can be estimated
      to be approximately 3% at pH 7. The BME binding kinetics, coupled with the
      kinetics of imidazole binding to G95P, allow us, for the first time, to specify
      all four rate constants describing the ligand binding reaction. Moreover, we can
      use the kinetic results to estimate the rate constants for ligand binding with
      the wild-type cytochrome c(2). This has also allowed us to quantify and more
      fully interpret cytochrome dynamics.

PMID- 12220528
TI  - Accelerated degradation of mislocalized UDP-glucuronosyltransferase family 1
      (UGT1) proteins in Gunn rat hepatocytes.
AB  - Gunn rat is a hyperbilirubinemic rat strain that is inherently deficient in the
      activity of UDP-glucuronosyltransferase form 1A1 (UGT1A1). A premature
      termination codon is predicted to produce truncated UGT1 proteins that lack the
      COOH-terminal 116 amino acids in Gunn rat. Pulse-chase experiments using primary
      cell cultures showed that the truncated UGT1A1 protein in Gunn rat hepatocytes
      was synthesized similarly to wild-type UGT1A1 protein in normal Wistar rat
      hepatocytes. However, the truncated UGT1A1 protein was degraded rapidly with a
      half-life of about 50 min, whereas the wild-type UGT1A1 protein had a much longer
      half-life of about 10 h. The rapid degradation of truncated UGT1A1 protein was
      inhibited partially but not completely by treating Gunn rat hepatocytes with
      proteasome inhibitors such as carbobenzoxy-Leu-Leu-leucinal and lactacystin. By
      contrast, neither the lysosomal cysteine protease inhibitor nor the calpain
      inhibitor slowed the degradation. Our findings show that the absence of UGT1
      protein from Gunn rat hepatocytes is due to rapid degradation of the truncated
      UGT1 protein by the proteasome and elucidate the molecular basis underlying the
      deficiency in bilirubin glucuronidation.

PMID- 12220529
TI  - Effects of cadmium and zinc on solar-simulated light-irradiated cells: potential
      role of zinc-metallothionein in zinc-induced genoprotection.
AB  - Zinc is an essential oligoelement for cell growth and cell survival and has been
      demonstrated to protect cells from oxidative stress induced by UVA or from
      genotoxic stress due to UVB. In a recent work we demonstrated that the
      antioxidant role of zinc could be related to its ability to induce
      metallothioneins (MTs). In this study we identified the mechanism of zinc
      protection against solar-simulated light (SSL) injury. Cultured human
      keratinocytes (HaCaT) were used to examine MTs expression and localization in
      response to solar-simulated radiation. We found translocation to the nucleus,
      with overexpression of MTs in irradiated cells, a novel observation. The
      genoprotective effect of zinc was dependent on time and protein synthesis. DNA
      damage was significantly decreased after 48 h of ZnCl(2) (100 microM) treatment
      and is inhibited by actinomycin D. ZnCl(2) treatment (100 microM) led to an
      intense induction, redistribution, and accumulation of MT in the nucleus of
      irradiated cells. MT expression correlated with the time period of ZnCl(2)
      treatment. CdCl(2), a potent MT inducer, did not show any genoprotection,
      although the MTs were expressed in the nucleus. Overall our findings demonstrate
      that MTs could be a good candidate for explaining the genoprotection mediated by
      zinc on irradiated cells.

PMID- 12220530
TI  - Anionic substitutes for catalytic aspartic acids in phosphoribulokinase.
AB  - Mutagenic substitution of the invariant D42 and D169 residues in
      phosphoribulokinase (PRK) with amino acids that contain neutral side chains
      (e.g., alanine or asparagine) results in large decreases in catalytic efficiency
      (10(5)- and 10(4)-fold for replacement of D42 and D169, respectively). To further
      evaluate the importance of anionic side chains at residues 42 and 169,
      substitutions of glutamic acid (D42E, D169E) and cysteine (D42C and D169C in an
      otherwise cysteine-free protein) have been engineered. All purified mutant
      enzymes bind the fluorescent alternative substrate trinitrophenyl-ATP and the
      allosteric effector NADH similarly to wild-type PRK. For D42E and D42C, V(max)
      exhibits substantial decreases of 135- and 220-fold, respectively. Comparable
      substitutions for D169 result in smaller effects; D169E and D169C exhibit
      decreases in V(max) of 39- and 26-fold, respectively. Thus, regardless of the
      type of substitution, changes at D42 more profoundly affect catalytic rate than
      do comparable changes at D169. Precedent with enzymes in which cysteine replaces
      an acidic residue suggests that oxidation of the thiolate to a sulfinate can
      convert low-activity cysteine mutants into enzymes with improved activity.
      Periodate oxidation of cysteine-free PRK results in a slight decrease in
      activity. In contrast, comparable treatment of D42C and D169C proteins increases
      activity by 5- and 7-fold, respectively. Thus, for reasonably efficient
      catalysis, PRK requires anionic character in the side chains of residues 42 and
      169. The enzyme can, however, tolerate substantial structural and chemical
      variability at these residues.

PMID- 12220531
TI  - Hepatocyte nuclear factor (HNF)-4 alpha/gamma, HNF-1 alpha, and vHNF-1 regulate
      the cell-specific expression of the human dihydrodiol dehydrogenase (DD)4/AKR1C4
      gene.
AB  - Recently, we found a region A (a hepatocyte nuclear factor (HNF)-4-binding site
      from nucleotides -701 to -684) and a region B (an HNF-1-binding site from
      nucleotides -682 to -666) as cis-acting elements necessary for the
      transcriptional activation of the human dihydrodiol dehydrogenase (DD)4 gene in
      human hepatoblastoma HepG2 cells, which express DD4 mRNA. Thus, to investigate
      the mechanism(s) responsible for the cell-type-specific expression of DD4 mRNA,
      we constructed a reporter plasmid, pDD4 Foot A+B: -95/+28, in which regions A and
      B were linked to the human DD4 minimal promoter (-95 to +28) fused to the
      luciferase gene. The luciferase activity was detectable in HepG2 cells but not in
      human renal adenocarcinoma ACHN cells transfected with the pDD4 Foot A+B: 
      95/+28, which do not express DD4 mRNA. A supershift assay using antibodies to HNF
      4 alpha, -4 gamma, -1 alpha, or valiant HNF (vHNF)-1 revealed that HNF-4 alpha, 
      4 gamma, and -1 alpha recognized regions A and B in HepG2 cells and that only
      vHNF-1 bound to regions A and B in ACHN cells. Semiquantitative reverse
      transcribed polymerase chain reaction showed that a large amount of vHNF-1-C,
      which lacked transcriptional activation domain, was expressed in ACHN cells.
      Transfection of ACHN cells with an expression plasmid of vHNF-1-C did not
      activate the pDD4 Foot A+B: -95/+28 reporter gene. Taken together, we conclude
      that the cell-type-specific expression of DD4 mRNA is regulated by vHNF-1-C.

PMID- 12220532
TI  - Secreted phosphatase activity induced by dimethyl sulfoxide in Herpetomonas
      samuelpessoai.
AB  - A phosphatase activity of the trypanosomatid parasite Herpetomonas samuelpessoai
      was characterized using intact living cells. The effects of dimethyl sulfoxide
      (DMSO) on this activity were investigated. This phosphatase activity (2.53+/-0.01
      nmol P(i)/mg protein x min) was linear with cell density and with time for at
      least 60 min. The optimum pH for the H. samuelpessoai phosphatase lies in the
      acid range. This phosphatase activity was inhibited by metal chelators and
      classical phosphatase inhibitors. A robust stimulation of the phosphatase
      activity was observed when the flagellates were grown in the presence of 4% DMSO,
      both when intact flagellates and when culture supernatant from those cells were
      assayed, as observed by biochemical and cytochemical analysis. We also
      demonstrate that DMSO induced the secretion and/or shedding of this phosphatase
      to the extracellular medium, with a possible involvement of protein kinase C in
      this process.

PMID- 12220533
TI  - CD40-mediated tumor necrosis factor receptor-associated factor 3 signaling
      upregulates IL-4-induced germline Cepsilon transcription in a human B cell line.
AB  - Induction of germline C epsilon transcription in B cells by IL-4, which is a
      critical initiating step for IgE class switching, is enhanced by CD40 engagement.
      Although signaling by CD40 is initiated by the binding of tumor necrosis factor
      receptor-associated factor (TRAF) family members to its cytoplasmic domain,
      whether those TRAF family proteins mediate enhancement of germline Cepsilon
      transcription is not evident. We report here that CD40-induced TRAF3-dependent
      activation of mitogen-activated protein kinase (MAPK)/extracellular signal
      regulated kinase (ERK) kinase 1 (MEK1) is involved in the upregulation of IL-4
      driven germline C epsilon transcription in a human Burkitt's lymphoma B cell
      line, DG75. Among the six known TRAF proteins, TRAF2, 3, 5, and 6 associated with
      CD40 in an unstimulated state, and the levels of these four proteins were
      unaffected by anti-CD40 stimulation. Antisense oligodeoxynucleotide (ODN) for
      TRAF3 inhibited CD40-induced activation of MEK1-ERK pathway by decreasing
      expression of TRAF3 protein, but antisense ODNs for TRAF2, 5, and 6 were
      ineffective. Furthermore, CD40-mediated enhancement of IL-4-driven germline C
      epsilon transcription was inhibited by antisense ODN for TRAF3 and by a MEK1
      inhibitor, PD98059. These results suggest that in DG75 cells, TRAF3-induced MEK1
      activation may be involved in CD40-mediated upregulation of IL-4-driven germline
      C epsilon transcription.

PMID- 12220534
TI  - Glycosphingolipids from Magnaporthe grisea cells: expression of a ceramide
      dihexoside presenting phytosphingosine as the long-chain base.
AB  - Magnaporthe grisea is a fungal pathogen that infects rice leaves and causes rice
      blast, a devastating crop disease. M. grisea produces active elicitors of the
      hypersensitive response in rice that were previously identified as ceramide
      monohexosides (CMHs). Using several chromatographic approaches, mass
      spectrometry, and nuclear magnetic resonance, we identified ceramide mono- and
      dihexosides (CDH) in purified lipid extracts from M. grisea cells. As described
      by other authors, CMH consists of a ceramide moiety containing 9-methyl-4,8
      sphingadienine in amidic linkage to 2-hydroxyoctadecenoic or 2
      hydroxyhexadecenoic acids and a carbohydrate segment consisting of one residue of
      glucose. CDHs, however, contain beta-galactose (1-->4)-linked to beta-glucose as
      sugar units and phytosphingosine as the long-chain base, bound to a C24 alpha
      hydroxylated fatty acid. To our knowledge, this is the first report on the
      occurrence of CDH in a fungal species and illustrates the existence of an
      alternative path of ceramide glycosylation in fungal cells.

PMID- 12220535
TI  - Changes in lipid mobility associated with alamethicin incorporation into
      membranes.
AB  - The binding state of the antibiotic peptide alamethicin with phospholipid
      bilayers was investigated in terms of the changes induced in lipid mobility.
      Fluorescence anisotropy was used for the study. It was found that an increase in
      peptide concentration induced different changes in lipid mobility above and below
      a critical peptide concentration. This concentration was also critical for an
      increase in the cooperative binding of the peptide, as detected by circular
      dichroism. Above the critical peptide concentration, the mobility of both lipid
      regions, around the polar head and hydrocarbon chain, became restricted with an
      increased peptide concentration. Below the critical level, however, an increased
      peptide concentration induced a "wobbling" of the lipid hydrocarbon chain. These
      results show that an increase in the cooperative binding of the peptide is
      accompanied by a change in the dominant configuration of the binding peptide.
      When the binding peptide increases, the dominant configuration appears to shift
      from surface association to deep incorporation within the membrane. This shift in
      configuration means that in the formation of ion-conductive pores, voltage-driven
      insertion of the peptide is a prominent step below a critical peptide
      concentration.

PMID- 12220536
TI  - Metal-mediated DNA damage induced by curcumin in the presence of human cytochrome
      P450 isozymes.
AB  - Although curcumin is known to exhibit antitumor activity, carcinogenic properties
      have also been reported. To clarify the potentiality of carcinogenesis by
      curcumin, we have examined whether curcumin can induce DNA damage in the presence
      of cytochrome P450 (CYP) using [32P]-5(')-end-labeled DNA fragments obtained from
      genes relevant to human cancer. Curcumin treated with CYP 2D6, CYP1A1, or CYP1A2
      induced DNA damage in the presence of Cu(II). CYP2D6-treated curcumin caused base
      damage, especially at 5(')-TG-3('), 5(')-GC-3('), and GG sequences. The DNA
      damage was inhibited by both catalase and bathocuproine, suggesting that reactive
      species derived from the reaction of H(2)O(2) with Cu(I) participate in DNA
      damage. Formation of 8-oxo-7,8-dihydro-2(')-deoxyguanosine was significantly
      increased by CYP2D6-treated curcumin in the presence of Cu(II). Time-of- flight
      mass spectrometry demonstrated that CYP2D6 catalyzed the conversion of curcumin
      to O-demethyl curcumin. Therefore, it is concluded that curcumin may exhibit
      carcinogenic potential through oxidative DNA damage by its metabolite.

PMID- 12220537
TI  - Activation of the mitochondrial caspase cascade in the absence of protein
      synthesis does not require c-Jun N-terminal kinase.
AB  - Prolonged activation of the c-Jun N-terminal kinase (JNK) has been suggested as a
      signal for apoptosis in response to a wide variety of stimuli. Using three
      cytocidal RNA or protein synthesis inhibitors (actinomycin D, anisomycin, and
      emetine), the potential role of JNK in activation of the mitochondrial apoptotic
      cascade was investigated in A549-S cells. Protein synthesis inhibition per se was
      not the cause of cell death as cycloheximide induced only growth arrest. All the
      cytocidal inhibitors induced cytochrome c release and caspases 9 activation
      within hours, but only anisomycin caused persistent JNK activation. Although, the
      JNK inhibitor, SP600125, inhibited JNK-dependent anisomycin-induced c-Jun
      phosphorylation, it was ineffective in preventing anisomycin-induced caspase
      activation and cell death. Thus, all three lethal macromolecule synthesis
      inhibitors can activate the mitochondrial apoptotic machinery independent of JNK
      activation, demonstrating that the mitochondrial apoptotic pathway can be
      activated independently of the JNK pathway in the absence of protein synthesis.

PMID- 12220538
TI  - Troponin T isoforms modulate calcium dependence of the kinetics of the cross
      bridge cycle: studies using a transgenic mouse line.
AB  - Alternative splicing of troponin T (TnT) in striated muscle during development
      results in expression of different isoforms, with the splicing of a 5(') exon of
      TnT resulting in the expression of low-molecular-weight basic adult TnT isoforms
      and high-molecular-weight acidic embryonic TnT isoforms. Although other
      differences exist, the main differences between cardiac TnT (cTnT) and fast
      skeletal muscle TnT (fTnT) are in the NH(2) terminus, with fTnT being less acidic
      than cTnT. A transgenic mouse line expressing chicken fTnT in the heart was used
      to investigate the functional significance of TnT NH(2)-terminal charge
      differences on cardiac muscle contractility. The rates of force redevelopment
      (k(tr)) at four levels of Ca(2+) activation were recorded for skinned left
      ventricular trabeculae from control and transgenic mice. The k(tr) vs Ca(2+)
      relationship was different in control mice and transgenic mice, suggesting that
      the structure of TnT, and possibly the NH(2)-terminal region, is involved in
      determining the kinetics of cross-bridge cycle. These results suggest that
      isoform shifts in TnT may be an important molecular mechanism for determining the
      Ca(2+) dependence of cardiac muscle contractility.

PMID- 12220539
TI  - Thiazolidinediones as a novel class of NAD(+)-dependent 15-hydroxyprostaglandin
      dehydrogenase inhibitors.
AB  - NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes NAD(+)
      dependent oxidation of prostaglandins and other nonprostanoid compounds. This
      enzyme was found to be dramatically induced in hormone-responsive human prostate
      cancer cells by androgens [M. Tong, and H. H. Tai, 2000, Biochem. Biophys. Res.
      Commun. 276, 77-81] and could be involved in prostate tumorigenesis. Inhibitors
      of this enzyme may be of value in determining the utility of these compounds in
      cancer chemoprevention. Previously, ciglitazone, an antidiabetic
      thiazolidinedione, was found to be a potent inhibitor of 15-PGDH. Structure
      activity analysis of available thiazolidinediones indicated that the nature of
      the moiety linking to phenyl ring through ether linkage and benzylidene
      configuration play important roles in inhibitory potency. Furthermore, N
      methylation of 2,4-thiazolidinedione abolished the inhibitory activity. A series
      of benzylidene thiazolidinediones with varied ring structure and methylene bridge
      to phenyl ring through ether linkage were synthesized and assayed for inhibitory
      activity. It was found that compound CT-8 (5-[4-(cyclohexylethoxy)benzylidene]
      2,4-thiazolidinedione) was the most potent inhibitor effective at nanomolar
      range. Kinetic studies revealed that inhibition by this compound was
      noncompetitive with respect to NAD(+) and uncompetitive with respect to
      prostaglandin E(2), indicating that the inhibitor interacts with the enzyme at a
      site distinct from the substrate binding site. This regulatory site appears to
      overlap with the activator site occupied by imipramine since activation of the
      enzyme by this activator is competitively inhibited by compound CT-8.

PMID- 12220540
TI  - Cyclosporin A-sensitive permeability transition pore is involved in Cd(2+)
      induced dysfunction of isolated rat liver mitochondria: doubts no more.
AB  - There is dose-dependent Cd(2+)-evoked swelling of isolated rat liver mitochondria
      energized by complex I, II, or IV respiratory substrates in sucrose medium in the
      absence of added Ca(2+) and P(i), which is prevented by Sr(2+). Permeability
      transition effectors (ADP, CsA, EGTA, RR, DTT, ATR, P(i), and Ca(2+)) affect in a
      corresponding way Cd(2+)-promoted membrane permeabilization in NH(4)NO(3), KCl,
      and sucrose media. Maximal depression of Cd(2+)-induced swelling is achieved by
      simultaneous addition of ADP, Mg(2+), and CsA that produces either synergistic
      (NH(4)NO(3)) or additive (KCl and sucrose media) action. Sustained activation by
      low [Cd(2+)] of mitochondrial basal respiration in KCl medium is observed both in
      the absence and in the presence of rotenone and/or oligomycin but only in the
      latter case (rotenone+oligomycin) CsA inhibits completely Cd(2+) activation of St
      4 respiration and partially reverses DNP-uncoupled respiration depressed by
      cadmium. Cd(2+) effects are discussed in terms of comparison with those of Zn(2+)
      and PhAsO.

PMID- 12220541
TI  - Multiple basic-leucine zipper proteins regulate induction of the mouse heme
      oxygenase-1 gene by arsenite.
AB  - The mechanism of heme oxygenase-1 (ho-1) gene activation by arsenite was
      examined. Arsenite-stimulated expression of a ho-1 promoter/luciferase chimera in
      a dose-dependent manner in mouse hepatoma (Hepa) cells. Mutation analyses
      identified the arsenite-responsive sequence as the stress-response element
      (StRE), which resembles the binding sites for the AP-1 superfamily of basic
      leucine zipper factors. In electrophoretic mobility shift assays, up to seven
      specific StRE-protein complexes were routinely detected using extracts from
      untreated Hepa cells whereas a single complex was typically observed after
      treatment with arsenite. Antibody "supershift" experiments identified Nrf2, JunD,
      and ATF3 in control complexes and the amount of these factors increased
      significantly in the arsenite-induced complex. MafG, ATF2, FosB, and JunB were
      also detected in the arsenite complex. Activation of a StRE-dependent luciferase
      gene by arsenite was inhibited to varying degrees by dominant-negative mutants of
      Nrf2, MafK, c-Fos, and CREB but most strongly with the latter. Together, these
      results implicate multiple basic-leucine zipper transcription factors in ho-1
      gene activation by arsenite.

PMID- 12220542
TI  - The hexosamine biosynthesis pathway regulates insulin secretion via protein
      glycosylation in mouse islets.
AB  - The hexosamine biosynthesis pathway plays a role in the modification of cellular
      proteins via the provision of substrate for addition of O-linked N
      acetylglucosamine (GlcNAc). The relative importance of the GlcNAc modification of
      proteins to insulin secretion from pancreatic beta-cells has not been
      investigated and so remains unclear. In the present study, we show that
      inhibition of the hexosamine biosynthesis pathway decreases insulin secretion
      from mouse islets in response to a number of secretagogues, including glucose.
      This impairment in beta-cell function could not be attributed to reduced islet
      insulin content, altered ATP levels, or cell death and was restored with the
      addition of N-acetylglucosamine, a substrate that enters the pathway below the
      point of inhibition. Western blot analysis revealed that decreased islet protein
      glycosylation paralleled the decrease in insulin secretion following inhibition
      of the pathway. In conclusion, the data suggest a role for the hexosamine
      biosynthesis pathway in regulating the secretion of insulin by altering protein
      glycosylation. This finding may have implications for the development of type 2
      diabetes, as chronic increase in flux through the hexosamine biosynthesis pathway
      may lead to the deterioration of beta-cell function via abnormal protein
      glycosylation.

PMID- 12220543
TI  - Low stability for monomeric human chaperonin protein 10: interprotein
      interactions contribute majority of oligomer stability.

PMID- 12220544
TI  - Cytokines in autoimmune disease and chronic inflammatory proliferative disease.

PMID- 12220545
TI  - Cytokines and anti-cytokine biologicals in autoimmunity: present and future.
AB  - The increasing understanding of the role of cytokines in autoimmunity, and the
      observation that tumour necrosis factor alpha (TNFalpha) is central to the
      inflammatory and destructive process common to several human autoimmune diseases,
      has led to a new generation of therapeutics, the TNFalpha blocking agents. In
      this article, we review the current knowledge of the role of cytokines in
      autoimmunity as unravelled by studies both in the laboratory and the clinic. In
      addition, we discuss future prospects of the anti-TNFalpha therapy that may
      involve combination therapy with other anti-cytokine or anti-T cell biologicals,
      or the use of small chemicals targeting molecules involved in TNFalpha production
      such as NF-kappaB and p38 MAPK. The future developments of anti-TNFalpha and anti
      cytokine therapy in general will be interesting.

PMID- 12220546
TI  - Role of TNF/TNFR in autoimmunity: specific TNF receptor blockade may be
      advantageous to anti-TNF treatments.
AB  - Deregulated TNF production, be it low or high, characterizes many autoimmune
      diseases. Recent evidence supports a dualistic, pro-inflammatory and immune- or
      disease-suppressive role for TNF in these conditions. Blocking TNF in autoimmune
      prone chronic inflammatory diseases may, therefore, lead to unpredictable
      outcomes, depending on timing and duration of treatment. Indeed, blockade of TNF
      in human rheumatoid arthritis or inflammatory bowel disease patients, although so
      far impressively beneficial for the majority of patients, it has also led to a
      significant incidence of drug induced anti-dsDNA production or even in
      manifestations of lupus and neuro-inflammatory disease. Notably, anti-TNF
      treatment of multiple sclerosis patients has led almost exclusively to immune
      activation and disease exacerbation. We discuss here recent evidence in murine
      disease models, indicating an heterogeneity of TNF receptor usage in autoimmune
      suppression versus inflammatory tissue damage, and put forward a rationale for a
      predictably beneficial effect of 'anti-TNFR' instead of 'anti-TNF' treatment in
      human chronic inflammatory and autoimmune conditions.

PMID- 12220547
TI  - The balance between IL-1 and IL-1Ra in disease.
AB  - IL-1 is an important mediator of inflammation and tissue damage in multiple
      organs, both in experimental animal models of disease and in human diseases. The
      IL-1 family consists of two agonists, IL-1alpha and IL-1beta, two receptors,
      biologically active IL-1RI and inert IL-1RII, and a specific receptor antagonist,
      IL-1Ra. The balance between IL-1 and IL-1Ra in local tissues plays an important
      role in the susceptibility to and severity of many diseases. An allelic
      polymorphism in the IL-1Ra gene has been associated with a variety of human
      diseases primarily of epithelial and endothelial cell origin. This association
      may be secondary to an imbalance in the IL-1 system with enhanced production of
      IL-1beta and reduced production of the major intracellular isoform of IL-1Ra.
      Treatment of RA with daily subcutaneous injections of recombinant IL-1Ra protein
      has been shown to be efficacious. Gene therapy approaches with IL-1Ra are being
      evaluated for the treatment of RA and other human diseases.

PMID- 12220548
TI  - Roles of IL-1 in the development of rheumatoid arthritis: consideration from
      mouse models.
AB  - Expression of inflammatory cytokines is augmented in the joints of patients with
      rheumatoid arthritis (RA). We found that cytokine levels are also elevated in the
      joints of a mouse arthritis model, human T-cell leukemia virus type I (HTLV-I)
      transgenic (Tg) mouse. Depletion of IL-1 by gene targeting greatly reduced the
      incidence of the disease, indicating the importance of this cytokine in the
      development of arthritis. Furthermore, IL-1 receptor antagonist (IL-1Ra)
      deficient mice develop autoimmunity and arthritis spontaneously. These
      observations suggest that excess IL-1 signaling the causes autoimmunity. We show
      that IL-1 activates the immune system non-specifically by inducing CD40L and OX40
      co-signaling molecules on T cells. In this review, the roles of IL-1 in the
      development of autoimmunity and arthritis in mouse models will be discussed.

PMID- 12220549
TI  - IL-6 in autoimmune disease and chronic inflammatory proliferative disease.
AB  - Interleukin 6 (IL-6), which was originally identified as a B-cell differentiation
      factor, is now known to be a multifunctional cytokine that regulates the immune
      response, hematopoiesis, the acute phase response, and inflammation. Deregulation
      of IL-6 production is implicated in the pathology of several disease processes.
      The expression of constitutively high levels of IL-6 in transgenic mice results
      in fatal plasmacytosis, which has been implicated in human multiple myeloma.
      Increased IL-6 levels are also observed in several diseases, including rheumatoid
      arthritis (RA), systemic-onset juvenile chronic arthritis (JCA), osteoporosis,
      and psoriasis. IL-6 is critically involved in experimentally induced autoimmune
      disease, such as antigen-induced arthritis (AIA), and experimental allergic
      encephalomyelitis. All these clinical data and animal models suggest that IL-6
      plays critical roles in the pathogenesis of autoimmune diseases. Here we review
      the evidence for the involvement of IL-6 in the pathophysiology of autoimmune
      diseases and chronic inflammatory proliferative diseases (CIPD) and discuss the
      possible molecular mechanisms of its involvement.

PMID- 12220550
TI  - IL-2 and autoimmune disease.
AB  - A decade after the first description of IL-2-deficient mice, the redundancy of IL
      2 as a T cell growth factor is well accepted and the focus of research has
      shifted to the unexpected multiorgan autoimmunity and inflammation observed in
      mice lacking components of the IL-2/IL-2R system. So far, a set of defects at the
      levels of repertoire selection, the generation of suppressive regulatory T cells,
      T cell homing and clonal contraction via activation induced cell death (AICD)
      have been documented. We propose that these individual defects jointly contribute
      to the severe disturbance of T cell homeostasis and self-tolerance underlying the
      immunopathology of the IL-2 deficiency syndrome.

PMID- 12220551
TI  - Type I interferons and autoimmunity: lessons from the clinic and from IRF-2
      deficient mice.
AB  - Type I interferons (IFN-alpha/beta) are produced upon viral and bacterial
      infections and play essential roles in host defense. However, since IFN
      alpha/beta have multiple regulatory functions on innate and adoptive immunity,
      dysregulation of the IFN-alpha/beta system both in uninfected hosts and during
      immune responses against infection can result in immunopathologies. In fact, IFN
      alpha/beta therapy often accompanies autoimmune-like symptoms. In this regard, we
      have recently found that mice lacking IFN regulatory factor (IRF)-2, a negative
      regulator of IFN-alpha/beta signaling, develop spontaneous, CD8(+) T cell
      dependent skin inflammation. This unique animal model, together with other animal
      models, highlights the importance of the mechanism maintaining the homeostasis in
      the IFN-alpha/beta system even in the absence of infection.

PMID- 12220552
TI  - Death receptor Fas and autoimmune disease: from the original generation to
      therapeutic application of agonistic anti-Fas monoclonal antibody.
AB  - Fas antigen (Fas) is a cell surface receptor molecule introducing apoptosis
      inducing signals into Fas-bearing cells by stimulation with Fas ligand or
      agonistic anti-Fas monoclonal antibodies. Fas system has been implicated in the
      regulation of homeostasis of peripheral T and B lymphocytes including elimination
      of autoreactive cells, and in the exclusion of tumor and virus-infected cells.
      Fas system, however, also plays a role in the mechanisms responsible for tissue
      disruption in tissue-specific autoimmune disease and fulminant hepatitis. In this
      review, I describe how we prepared the original anti-human Fas monoclonal
      antibody with associated cell-killing activity, and I propose here a strategy of
      therapeutic use of a novel anti-Fas monoclonal antibody for autoimmune and other
      diseases.

PMID- 12220553
TI  - The role of interleukin-10 in autoimmune disease: systemic lupus erythematosus
      (SLE) and multiple sclerosis (MS).
AB  - Interleukin-10 (IL-10) is an immunoregulatory cytokine that plays a crucial role
      in inflammatory and immune reactions. It has potent anti-inflammatory and
      immunosuppressive activities on myeloid cell functions which forms a solid basis
      for its use in acute and chronic inflammatory diseases. Here, we discuss the role
      of IL-10 in autoimmune diseases and examine its beneficial effects in cellular
      based autoimmune diseases such as multiple sclerosis (MS) or its involvement in
      humoral-based autoimmune diseases such as systemic lupus erythematosus (SLE).
      Inhibition of the immune stimulatory activities of IL-10 may provide novel
      approaches in the treatment of humoral autoimmune diseases, infectious diseases
      and cancer.

PMID- 12220555
TI  - Immunostaining of cholinergic pontomesencephalic neurons for alpha 1 versus alpha
      2 adrenergic receptors suggests different sleep-wake state activities and roles.
AB  - Cholinergic neurons of the pontomesencephalic tegmentum play a critical role in
      paradoxical sleep, when, according to single unit recording of 'possibly'
      cholinergic neurons, they fire maximally. The profile of activity of the
      cholinergic neurons may be determined by noradrenergic locus coeruleus neurons
      that are active during waking and silent during paradoxical sleep. Indeed, a
      permissive role of the noradrenergic neurons in paradoxical sleep has been
      proposed based upon an inhibitory action of noradrenaline through alpha(2)
      adrenergic receptors on the cholinergic cells. Yet some 'possibly' cholinergic
      neurons are purportedly maximally active during waking and excited by
      noradrenaline through alpha(1) receptors. In the present study, we examined by
      fluorescent dual-immunostaining in the laterodorsal and pedunculopontine
      tegmental nuclei of the rat whether choline acetyltransferase-immunopositive
      neurons are stained for alpha(2A) or alpha(1A) adrenergic receptors. For
      comparison, we examined immunostaining for these receptors on tyrosine
      hydroxylase-immunopositive locus coeruleus neurons, which are known to bear
      alpha(2A) autoreceptors. Whereas virtually all the noradrenergic neurons were
      labeled for the alpha(2A) and none for the alpha(1A), approximately half the
      cholinergic neurons were labeled for the alpha(2A) and one third for the
      alpha(1A) adrenergic receptors in adjacent sections. These results suggest that
      different groups of cholinergic neurons bear alpha(2) versus alpha(1) adrenergic
      receptors and would accordingly have different sleep-wake state activities and
      roles. The alpha(2)-bearing group would be inhibited by noradrenaline during
      waking to become disinhibited and maximally active while promoting paradoxical
      sleep, whereas the alpha(1)-bearing group would be excited by noradrenaline
      during waking to become maximally active while promoting features of that state.

PMID- 12220554
TI  - Regulation of cytokine signaling and inflammation.
AB  - Inflammation progresses by the action of pro-inflammatory cytokines, including
      interleukin-1 (IL-1), the tumor necrosis factor (TNF), gamma-interferon
      (IFNgamma), IL-12, IL-18, and the granulocyte-macrophage colony-stimulating
      factor, and is resolved by anti-inflammatory cytokines such as IL-4, IL-10, IL
      13, IFNalpha, and the transforming growth factor (TGF)beta. The intracellular
      signal transduction pathways of these cytokines have been studied extensively,
      and these pathways ultimately activate transcription factors, such as NF-kappaB,
      Smad, and STATs. Recently, the negative-feedback regulation of these pathways has
      been identified. In this review, we provide examples of the relationship between
      cytokine signal transduction, negative-signal regulation, and inflammatory
      disease models. Furthermore, we illustrate several approaches for treating
      inflammatory diseases by modulating extracellular and intracellular signaling
      pathways.

PMID- 12220556
TI  - Decreased inflammatory pain due to reduced carrageenan-induced inflammation in
      mice lacking adenosine A3 receptors.
AB  - Mice with a targeted disruption of adenosine A(3) receptor (A(3)AR) gene were
      assessed for their nociceptive threshold and for their localized inflammatory
      response following carrageenan injected into the hindpaw. Under basal conditions
      no difference was seen between A(3)AR knock-out (A(3)AR(-/-)) and wild-type
      (A(3)AR(+/+)) mice in nociceptive response to mechanical or heat stimuli. The
      antinociceptive response to the intrathecal adenosine analogue R-phenylisopropyl
      adenosine (R-PIA) was also unchanged in the A(3)AR(-/-) mice. In contrast, heat
      hyperalgesia, plasma extravasation and edema following carrageenan-induced
      inflammation in the hind paw were significantly reduced in A(3)AR(-/-) mice
      compared to the A(3)AR(+/+) controls. Thus, mice lacking A(3)AR had deficits in
      generating the localized inflammatory response to carrageenan, supporting a pro
      inflammatory role of A(3)AR in peripheral tissues. However, no evidence for a
      role of A(3)AR in nociception and the antinociceptive effect of R-PIA was found.

PMID- 12220557
TI  - Chronic neuropathic pain is accompanied by global changes in gene expression and
      shares pathobiology with neurodegenerative diseases.
AB  - Neuropathic pain is induced by injury or disease of the nervous system. Studies
      aimed at understanding the molecular pathophysiology of neuropathic pain have so
      far focused on a few known molecules and signaling pathways in neurons. However,
      the pathophysiology of neuropathic pain appears to be very complex and remains
      poorly understood. A global understanding of the molecular mechanisms involved in
      neuropathic pain is needed for a better understanding of the pathophysiology and
      treatment of neuropathic pain. Towards this end, we examined global gene
      expression changes as well as the pathobiology at the cellular level in a spinal
      nerve ligation neuropathic pain model using DNA microarray, quantitative real
      time PCR and immunohistochemistry. We found that the behavioral hypersensitivity
      that is manifested in the persistent pain state is accompanied by previously
      undescribed changes in gene expression. In the DRG, we found regulation of: (1)
      immediate early genes; (2) genes such as ion channels and signaling molecules
      that contribute to the excitability of neurons; and (3) genes that are indicative
      of secondary events such as neuroinflammation. In addition, we studied gene
      regulation in both injured and uninjured DRG by quantitative PCR, and observed
      differential gene regulation in these two populations of DRGs. Furthermore, we
      demonstrated unexpected co-regulation of many genes, especially the activation of
      neuroinflammation markers in both the PNS and CNS. The results of our study
      provide a new picture of the molecular mechanisms that underlie the complexity of
      neuropathic pain and suggest that chronic pain shares common pathobiology with
      progressive neurodegenerative disease.

PMID- 12220558
TI  - Expression and function of A1 adenosine receptors in the rat hippocampus
      following transient forebrain ischemia.
AB  - We investigated how transient cerebral ischemia affects the gene expression,
      immunoreactive protein levels, and the function of the A1 subtype of adenosine
      receptor in the rat hippocampus at different times following reperfusion. A1
      receptor mRNA levels were altered significantly in different hippocampal
      subfields as early as 6 h following insult. However, these changes in mRNA levels
      were not paralleled at the protein level, as western blotting with A1 receptor
      specific antibodies revealed that hippocampal A1 adenosine receptor prevalence
      did not differ from sham control at either 6 or 24 h following insult. The lack
      of change in A1 receptor prevalence was consistent with functional examinations,
      as only marginal changes were observed in the ability of A1 receptors to
      attenuate excitatory post-synaptic potentials in the CA1 subfield at 24 h
      following reperfusion. These data illustrate that although the mRNA expression
      levels of the A1 adenosine receptor are altered by transient cerebral ischemia,
      the immunoreactive prevalence and function of this receptor are maintained in the
      post-ischemic hippocampus at times preceding the death of the vulnerable neurons.

PMID- 12220559
TI  - Regulation of transcription factor phosphorylation by metabotropic glutamate
      receptor-associated signaling pathways in rat striatal neurons.
AB  - The group I metabotropic glutamate receptors (mGluRs) are positively coupled to
      phospholipase C. Through phospholipase C, group I mGluR activation increases
      intracellular concentrations of diacylglycerol which is known as a strong
      activator of protein kinase C (PKC). This study investigated the putative role of
      PKC in the regulation of transcription factor phosphorylation induced by group I
      mGluR activation in the rat striatum in vivo. We found that the group I agonist
      3,5-dihydroxyphenylglycine (DHPG) injected into the dorsal striatum (caudate
      putamen) increased phosphorylation of the two transcription factors, cAMP
      response element-binding protein (CREB) and Elk-1, and extracellular signal
      regulated kinase 1/2 (ERK1/2) in the injected striatum. Inhibition of PKC with
      GF109203X significantly attenuated DHPG-stimulated CREB, Elk-1, and ERK1/2
      phosphorylation. Activation of PKC with intracaudate injection of 12-O
      tetradecanoylphorbol-13-acetate (TPA) mimicked DHPG actions in facilitating the
      phosphorylation of CREB, Elk-1, and ERK1/2. Blockade of N-methyl-D-aspartate
      (NMDA) glutamate receptors with the non-competitive antagonist MK801 or the
      competitive antagonist AP5 attenuated TPA-induced CREB, Elk-1, and ERK1/2
      phosphorylation. Similarly, inhibition of Ca(2+)/calmodulin-dependent protein
      kinases (CaMK) with KN62 also resulted in a significant attenuation of TPA
      induction of the three phosphoproteins. The data obtained from this study
      indicate that selective activation of PKC is needed for the group I agonist
      induced CREB, Elk-1, and ERK1/2 phosphorylation in striatal neurons. Activated
      PKC may, at least in part, facilitate the phosphorylation of transcription
      factors via an NMDA/CaMK-sensitive pathway.

PMID- 12220560
TI  - Regional expression of the homeobox gene NKX2-1 defines pallidal and
      interneuronal populations in the basal ganglia of amphibians.
AB  - The distribution of gene expression domains during development constitutes a
      novel tool for the identification of distinct brain regions. This is particularly
      useful in the brain of amphibians where cell migration is very limited and most
      neurons organize in a periventricular layer. Here we report the expression
      pattern of NKX2-1 protein in the developing Xenopus telencephalon. In mammals,
      the Nkx2-1 gene is expressed in distinct subpallial regions such as the septum,
      the medial ganglionic eminence and preoptic region. The results of the present
      study demonstrate that the expression of NKX2-1 delineates the pallidal anlage
      and its derivatives in amphibians, as in mammals and birds. In addition, double
      labeling immunohistochemistry and the combination of tracing experiments with
      NKX2-1 immunohistochemistry demonstrate that the amphibian striatum contains
      interneurons, which express NKX2-1 and produce, among other possible
      neurotransmitters, nitric oxide and acetylcholine. In sum, the results of the
      present study strengthen the notion that similar developmental programs exist
      during basal ganglia development in all tetrapods.

PMID- 12220561
TI  - Effect of prenatal auditory enrichment on developmental expression of
      synaptophysin and syntaxin 1 in chick brainstem auditory nuclei.
AB  - Neural activity plays an important role in shaping the developing brain. We have
      determined the consequence of increased auditory stimulation on the developmental
      profile of synaptic proteins, synaptophysin and syntaxin 1, in the chick
      brainstem auditory nuclei, nucleus magnocellularis and nucleus laminaris, by
      immunohistochemistry and western blotting techniques. The chick embryos were
      provided with patterned sounds of species-specific calls or musical notes of a
      sitar, a stringed instrument, in a graded manner from embryonic day 10 (E10)
      through hatching, for 15 min every hour. During normal synaptogenesis of nucleus
      magnocellularis and nucleus laminaris, synaptophysin immunoreactivity increased
      significantly from E8 to E20, in parallel with synapse formation, and reduced at
      hatching. The embryos receiving species-specific sound stimuli exhibited a
      similar pattern with higher levels of immunoreactivity, though the difference
      between the study groups was not statistically significant. The music stimulated
      embryos showed an earlier peak at E16, followed by a gradual decline until
      hatching. In all three groups studied, syntaxin immunoreactivity showed a surge
      at E12, followed by a decline at E16 and subsequent stabilization. The stimulated
      groups continually expressed higher amounts of syntaxin immunoreactivity. The
      results suggest that prenatal sound stimulation enhances the normal pattern of
      synaptic protein expression in these auditory nuclei.

PMID- 12220562
TI  - Impaired central stress-induced release of noradrenaline in rats with heart
      failure: a microdialysis study.
AB  - Sympathetic hyperactivity in rats with heart failure is associated with increased
      extracellular noradrenaline in the hypothalamic paraventricular nucleus at rest.
      However, it is unknown how this nucleus responds to stressful stimuli. In the
      present study we therefore examined the basal and stress-induced release of
      noradrenaline in the paraventricular nucleus of conscious Sprague-Dawley rats
      with heart failure measured by in vivo microdialysis. Basal noradrenaline
      concentration in the paraventricular nucleus of rats with heart failure was more
      than double that in sham-operated controls. Immobilization stress decreases
      noradrenaline levels in the paraventricular nucleus of rats with heart failure to
      57% of baseline, while it increased in sham-operated controls to 228%. However,
      serum corticosterone was similarly elevated at 30 and 90 min post-stress in both
      experimental groups. We have shown that heart failure causes an impairment of the
      central noradrenergic system's response to acute sympatho-excitation but does not
      affect the hypothalamo-pituitary-adrenocortical response.

PMID- 12220563
TI  - The non-immunosuppressive immunophilin ligand GPI-1046 potently stimulates
      regenerating axon growth from adult mouse dorsal root ganglia cultured in
      Matrigel.
AB  - We used explant cultures of adult mouse dorsal root ganglia with spinal nerve
      attached growing in Matrigel to assess the effects of the non-immunosuppressive
      immunophilin ligand GPI-1046 [Snyder et al. (1998) TIPS 19, 21-26] on the growth
      rate of regenerating sensory axons and found a potent stimulation of axon growth.
      In these explant cultures, naked, unfasciculated axons emerge from the cut end of
      the spinal nerve and continue to grow in the Matrigel for up to eight days [Tonge
      et al. (1996) Neuroscience 73, 541-551]. Some axons are entirely smooth whilst
      others show prominent varicosities. Some of the former express the phosphorylated
      neurofilament epitope recognised by monoclonal antibody RT97, a marker for large
      calibre, myelinated axons, whilst the latter express calcitonin gene-related
      peptide, predominantly a marker for unmyelinated, and small diameter myelinated
      sensory axons. Many of the axons in these cultures also express the low-affinity
      neurotrophin receptor p75. GPI-1046 has been shown to have striking stimulatory
      effects on embryonic primary sensory axons growing in vitro and it was therefore
      of interest to see whether it could also enhance regenerating sensory axon growth
      from the adult ganglia in our cultures. GPI-1046 potently stimulated axon growth
      in our cultures in a dose-dependent manner. The stimulatory effect was not
      dependent on the class of sensory axon. These observations show that GPI-1046 is
      a potent stimulator of regenerating axons from adult, primary sensory neurones.
      The cellular site of action of GPI-1046 is unknown. To distinguish between a
      direct effect of the drug on neurones and an indirect effect we compared the
      effects of GPI-1046 on explant and dissociated cultures. In confirmation of
      previous results, we found that GPI-1046 potently stimulated axon outgrowth from
      explants of embryonic chick dorsal root ganglia. However, the drug was without
      effect on dissociated embryonic dorsal root ganglion neurones, suggesting that
      non-neuronal cells are important for axon growth stimulation.

PMID- 12220564
TI  - Preprodynorphin-, preproenkephalin-, preprotachykinin A- and preprotachykinin B
      immunoreactive neurons in the accumbens nucleus and olfactory tubercle: double
      immunofluorescence analysis.
AB  - Preprodynorphin (PPD), preproenkephalin (PPE) and preprotachykinins A (PPTA) and
      B (PPTB) are known to be expressed by neostriatal projection neurons. In the
      present study, we investigated the distributions and colocalizations of
      immunoreactivities for those prepropeptides in the ventral striatum, such as the
      accumbens nucleus (Acb) and olfactory tubercle (OT). Antibodies raised against C
      terminal portions of the prepropeptides labeled cell bodies of neurons with
      diameters of 8-15 microm. PPD-, PPE- and PPTA-immunoreactive neurons were
      distributed throughout the Acb and concentrated in the dense cell layer of the
      OT. PPTB-immunoreactive neurons were observed to form cell clusters, which were
      localized in mu-opioid receptor-immunoreactive patchy regions in the Acb, but
      were very rarely found in the dense cell layer of the OT. Double
      immunofluorescence analysis revealed that PPD, PPE and PPTB immunoreactivities
      were shown in 69%, 19% and 14% of PPTA-immunoreactive neurons, respectively, in
      the Acb core region, and in 92%, 7% and 25% of PPTA-immunoreactive neurons,
      respectively, in the Acb shell region. In the olfactory bulb, 51%, 19% and 3% of
      PPTA-immunoreactive neurons showed PPD, PPE and PPTB immunoreactivities,
      respectively. PPD and PPE immunoreactivities were rarely coexpressed in single
      neurons of all striatal regions. The present results indicated that, although
      PPTA and PPE were occasionally coexpressed in single neurons of the ventral
      striatum, the segregated expression of PPD and PPE in the ventral striatum was
      similar to that in the dorsal striatum. The clustered localization of PPTB
      expressing neurons in the Acb and near absence of PPTB-expressing neurons in the
      dense cell layer of the OT suggests that neurokinin B is a key substance in
      differentiating between the ventral and dorsal striatal regions.

PMID- 12220565
TI  - Recovery of type I fiber regionalization in gastrocnemius medialis of the rat
      after reinnervation along original and foreign paths, with and without muscle
      rotation.
AB  - After reinnervation following transection of the sciatic nerve, normal patterns
      of regional type I fiber distribution are known to return in rat hindlimb
      muscles. Here we investigate how this recovery is influenced by experimental
      conditions. In an initial operation, the nerve of gastrocnemius medialis (GM) of
      adult rats was cut close to the muscle and reinserted either (i) close to the
      original nerve entry, or (ii) at a more medial 'foreign' site. In other groups of
      animals, these nerve operations were combined with a rotation of the GM muscle
      around its longitudinal axis, trying to ascertain whether the position of the
      muscle within the limb was of importance for the reinnervation processes. In a
      control group the muscle was rotated but innervation remained intact. After 21
      weeks, the GM muscles were removed from both hindlimbs. Cross-sections were cut
      at seven different levels along each muscle, and 'slow' type I fibers were
      identified after staining for myofibrillar ATPase. The topographical positions
      were mapped out for all type I fibers. In all reinnervated muscles, an extensive
      type I fiber grouping was seen, indicating a widespread respecification of muscle
      fiber properties by ingrowing 'slow' axons. Normal topographical directions of
      type I fiber regionalization were about equally well restored in groups with the
      nerve inserted at the original or at the foreign site. In rotated muscles, the
      direction of type I fiber regionalization was significantly less rotated than the
      muscle as a whole. The results suggest that ingrowing 'slow' motor axons are
      guided toward their normal 'slow' regions by clues which are largely independent
      of the i.m. path of regeneration (original vs. foreign nerve entry site) but
      partly dependent on the position of the target muscle within the limb (rotated
      vs. non-rotated cases).

PMID- 12220566
TI  - Apolipoprotein E knockout mice display procedural deficits in the Morris water
      maze: analysis of learning strategies in three versions of the task.
AB  - Apolipoprotein E knockout (apoEKO) mice have been shown to be impaired in the
      spatial Morris water maze (MWM). However, several groups failed to replicate this
      finding. One reason for this inconsistency may stem from variations in the
      experimental protocols and environment between laboratories. In the present
      study, we have tested if age and variations in protocol implementation that
      specifically affect salience of the visual extramaze cues influence performance
      and navigational strategies in the MWM. We tested three- and 12-month-old apoEKO
      and wild type mice in three versions of the MWM differing on the availability of
      visual extramaze cues: (1) salient cues, (2) diffuse cues, and (3) absence of
      cues. Our results show that the presence of salient cues enhances acquisition
      performance of wild type, but not apoEKO mice in the MWM. This effect was
      restricted to the acquisition phase since apoEKO mice reached a level of
      performance that was comparable to that of controls toward the end of the task.
      No significant differences were detected between apoEKO and controls in either
      the diffuse cues or absence of cues paradigms. Thigmotaxic tendencies were
      observed in apoEKO mice and correlated high latency scores. Thigmotaxis may have
      interfered with the initial ability to engage in a proficient navigational
      strategy. These findings suggest that, in contrast to what has been proposed in
      the past, apoEKO mice appear not to be impaired in spatial memory per se but are
      deficient in a procedural component of the MWM. Furthermore, the procedural
      deficit and corresponding thigmotaxic tendencies of apoEKO mice appeared to
      increase with age. Taken together, these findings confirm our hypothesis that age
      and variations in experimental protocols can influence MWM performances.

PMID- 12220567
TI  - The influence of chemical sympathectomy on pain responsivity and alpha 2
      adrenergic antinociception in neuropathic animals.
AB  - We studied the effect of chemical sympathectomy by 6-hydroxydopamine (6-OHDA) on
      pain behavior and alpha(2)-adrenergic antinociception in rats with a spinal nerve
      ligation-induced neuropathy. For assessment of alpha(2)-adrenergic
      antinociception, the rats were treated systemically with two alpha(2)
      adrenoceptor agonists, one of which only poorly (MPV-2426) and the other very
      well (dexmedetomidine) penetrates the blood-brain barrier. Moreover, the effect
      of MPV-2426 on spontaneous activity of dorsal root nerve fibers proximal to the
      nerve injury was determined. Systemic treatment with 6-OHDA produced a marked
      decrease in immunocytochemical labeling of sympathetic nerve fibers in the skin
      but it produced no marked change in basal pain sensitivity to mechanical
      stimulation either in neuropathic or sham-operated animals. Systemic
      administration of MPV-2426 and dexmedetomidine produced a dose-dependent tactile
      antiallodynic effect in neuropathic animals. Intraplantar injection of MPV-2426
      had an identical antiallodynic effect independent of whether it was injected into
      the neuropathic or contralateral hindpaw. In a test of mechanical nociception and
      hyperalgesia, dexmedetomidine markedly attenuated pain responses in all
      experimental groups, whereas MPV-2426 had a weak but significant pain attenuating
      effect only in neuropathic animals. In the tail flick test, both alpha(2)
      adrenoceptor agonists had a significant antinociceptive effect. The pain
      attenuating effect of MPV-2426 was enhanced by pretreatment with 6-OHDA, except
      in a test of tactile allodynia. MPV-2426-induced modulation of spontaneous
      activity was not a general property of dorsal root fibers proximal to the injury.
      The results indicate that a chemical destruction of sympathetic postganglionic
      nerve fibers innervating the skin does not markedly influence cutaneous pain
      sensitivity nor is it critical for the alpha(2)-adrenoceptor agonist-induced
      attenuation of pain behavior in neuropathic or non-neuropathic animals. Chemical
      sympathectomy, independent of neuropathy, enhanced the pain attenuating effect by
      MPV-2426, probably due to a peripheral action, whereas in non-sympathectomized
      control and neuropathic animals peripheral mechanisms have only a minor, if any,
      role in the alpha(2)-adrenoceptor agonist-induced antinociception.

PMID- 12220568
TI  - Manganese influences the levels of neurotransmitters in synapses in rat brain.
AB  - 54Mn previously taken up by the amygdala is released along with known
      neurotransmitters into the extracellular space during stimulation with 100 mM
      KCl. The possibility of manganese release from neuron terminals in a calcium- and
      impulse-dependent manner was examined by using the in vivo microdialysis method
      in the present study. The increase of (54)Mn release into the amygdalar
      extracellular space during stimulation with high K(+) was inhibited by addition
      of 1 microM tetrodotoxin. This increase of (54)Mn release into the extracellular
      space by stimulation with high K(+) was also observed in the hippocampus, but not
      in the substantia nigra. The increment of glutamate in the extracellular space
      during stimulation with high K(+) was highly correlated with that of (54)Mn,
      suggesting that manganese is concurrently released with glutamate from neuron
      terminals. The level of (54)Mn in the extracellular space in the hippocampus was
      increased with that of glutamate, but not with those of GABA and glycine, during
      stimulation with 100 mM KCl in the presence of 30 microM kainate. This increase
      was more marked than during stimulation with 30 microM kainate alone. It is
      likely that manganese is released from glutamatergic neuron terminals. When the
      rat hippocampus was perfused with artificial cerebrospinal fluid containing 20 or
      200 nM MnCl(2), the levels of glutamate, aspartate and GABA in the perfusate were
      dose-dependently decreased during perfusion with manganese. The present findings
      demonstrate that manganese released into the synaptic cleft may influence
      synaptic neurotransmission.

PMID- 12220569
TI  - GABA(A) receptor regulation of kyphotic nursing and female sexual behavior in the
      caudal ventrolateral periaqueductal gray of postpartum rats.
AB  - Bilateral lesions of the ventrolateral caudal periaqueductal gray inhibit
      lordosis and kyphosis, the postures of female sexual receptivity and maternal
      nursing that are characterized respectively by dorsoflexion and ventroflexion of
      the spinal column. These lesions also inhibit the solicitation behaviors that
      accompany lordosis, but they do not impair retrieval or licking of pups. We
      tested the hypothesis that reproductive behaviors affected by these lesions are
      tonically inhibited by activity of the GABA(A) receptor via site-specific
      manipulations of receptor activity. Rats were bilaterally implanted during
      pregnancy with guide cannulae aimed at the caudal periaqueductal gray and
      ovariectomized on day 1 postpartum. Microinfusions (0.25 microl/side) of saline
      or drug took place on days 5 and 7 postpartum into the dorsolateral column and on
      days 9 and 11 into the ventrolateral column. Five minutes post-infusion dams were
      reunited with their pups and their maternal behavior was observed for 30 min.
      Feminine sexual behaviors were evaluated post-weaning after another set of
      microinfusions in the ventrolateral caudal periaqueductal gray. Potential
      facilitation of kyphosis and lordosis was tested with the GABA(A) antagonist
      bicuculline (15 ng/side) during sub-threshold conditions, i.e., non-suckling pups
      or sub-threshold ovarian hormone dosages; potential inhibition of these postures
      was tested with the GABA(A) agonist muscimol (125 ng/side) during optimal
      conditions, i.e., suckling pups or supra-threshold ovarian hormone treatments.
      Dorsolateral drug manipulations were ineffective. In the ventrolateral
      periaqueductal gray bicuculline significantly increased and muscimol
      significantly decreased kyphosis, lordosis, and sexual solicitations compared
      with saline. Retrieval and licking of pups were not altered by GABA(A)
      manipulations. These findings suggest that the reproductive postures of female
      rats, lordosis and kyphosis, as well as sexual solicitations, are tonically
      inhibited by the neurotransmitter GABA within the ventrolateral caudal
      periaqueductal gray in the midbrain. In contrast, retrieval and licking of pups
      appear to be under separate neurochemical or neuroanatomical control, or both.
      Further, this tonic inhibition is likely relieved by excitatory somatosensory
      inputs to this site, from mounting and suckling respectively.

PMID- 12220570
TI  - Go6976 inhibits LPS-induced microglial TNFalpha release by suppressing p38 MAP
      kinase activation.
AB  - Microglial responses to endotoxin, including the synthesis of inflammatory
      factors, contribute to gliosis and neuron degeneration in cultured brain tissue.
      We have previously shown that Go6976, a protein kinase C (PKC) inhibitor,
      suppressed the lipopolysaccharide (LPS)-induced production of inflammatory
      factors in microglia and afforded marked protection of neurons from glia-mediated
      cytotoxicity. The purpose of this study was to identify the signal transduction
      pathway underlying the neuroprotective effect of Go6976. Go6976 suppressed the
      LPS-induced release of tumor necrosis factor alpha (TNFalpha) in the microglial
      cell line, BV2. We show in this study the inhibitory effect of Go6976 on TNFalpha
      release occurring through suppression of p38 mitogen-activated protein kinase
      (MAPK) phosphorylation and not through a PKC mechanism. While Go6976 did not
      inhibit the activity of p38 MAPK directly, it did suppress its activation by
      phosphorylation, indicating the target of action of Go6976 is a signaling event
      upstream of p38 MAPK. Although Go6976 is considered a selective inhibitor of
      certain PKC isozymes, suppression of TNFalpha production was not mediated through
      inhibition of PKC activity. Go6976 appears to play a novel role in
      neuroprotection by suppressing the release of pro-inflammatory factors by
      inhibiting the activation of p38 MAPK in microglia, rather than a PKC isoform.

PMID- 12220571
TI  - Properties of glutaminase of crayfish CNS: implications for axon-glia signaling.
AB  - Glutaminase of crayfish axons is believed to participate in recycling of axon
      glia signaling agent(s). We measured the activity and properties of glutaminase
      in crude homogenates of crayfish CNS, using ion exchange chromatography to
      separate radiolabeled product from substrate. Crayfish glutaminase activity is
      cytoplasmic and/or weakly bound to membranes and dependent on time, tissue
      protein, and glutamine concentration. It resembles the kidney-type phosphate
      activated glutaminase of mammals in being stimulated by inorganic phosphate and
      alkaline pH and inhibited by the product glutamate and by the glutamine analog 6
      diazo-5-oxo-L-norleucine. During incubation of crayfish CNS fibers in Na(+)-free
      saline containing radiolabeled glutamine, there is an increased formation of
      radiolabeled glutamate in axoplasm that is temporally associated with an increase
      in axonal pH from about 7.1 to about 8.0. Both the formation of glutamate and the
      change in pH are reduced by 6-diazo-5-oxo-L-norleucine. Our results suggest that
      crayfish glutaminase activity is regulated by cellular changes in pH and
      glutamate concentration. Such changes could impact availability of the axon-glia
      signaling agents glutamate and N-acetylaspartylglutamate.

PMID- 12220572
TI  - Lysergic acid diethylamide-induced Fos expression in rat brain: role of serotonin
      2A receptors.
AB  - Lysergic acid diethylamide (LSD) produces altered mood and hallucinations in
      humans and binds with high affinity to serotonin-2A (5-HT(2A)) receptors.
      Although LSD interacts with other receptors, the activation of 5-HT(2A) receptors
      is thought to mediate the hallucinogenic properties of LSD. The goal of this
      study was to identify the brain sites activated by LSD and to determine the
      influence of 5-HT(2A) receptors in this activation. Rats were pretreated with the
      5-HT(2A) receptor antagonist MDL 100907 (0.3 mg/kg, i.p.) or vehicle 30 min prior
      to LSD (500 microg/kg, i.p.) administration and killed 3 h later. Brain tissue
      was examined for Fos protein expression by immunohistochemistry. LSD
      administration produced a five- to eight-fold increase in Fos-like
      immunoreactivity in medial prefrontal cortex, anterior cingulate cortex, and
      central nucleus of amygdala. However, in dorsal striatum and nucleus accumbens no
      increase in Fos-like immunoreactivity was observed. Pretreatment with MDL 100907
      completely blocked LSD-induced Fos-like immunoreactivity in medial prefrontal
      cortex and anterior cingulate cortex, but only partially blocked LSD-induced Fos
      like immunoreactivity in amygdala. Double-labeled immunohistochemistry revealed
      that LSD did not induce Fos-like immunoreactivity in cortical cells expressing 5
      HT(2A) receptors, suggesting an indirect activation of cortical neurons. These
      results indicate that the LSD activation of medial prefrontal cortex and anterior
      cingulate cortex is mediated by 5-HT(2A) receptors, whereas in amygdala 5-HT(2A)
      receptor activation is a component of the response. These findings support the
      hypothesis that the medial prefrontal cortex, anterior cingulate cortex, and
      perhaps the amygdala, are important regions involved in the production of
      hallucinations.

PMID- 12220573
TI  - Involvement of the medial prefrontal cortex in mediating behavioural responses to
      odour cues rather than olfactory recognition memory.
AB  - Sheep form an olfactory recognition memory for their lambs within 2 h of
      parturition and will subsequently reject the approaches of any strange lamb and
      protest vocally. In this study we report that following olfactory memory
      formation, ewes exposed to either their own or a strange lamb show c-fos mRNA
      expression in the medial frontal cortex, although levels of expression in the
      pyramidal output cell layer V were significantly higher in ewes that rejected
      strange lambs. Reversibly inactivating this region by the retrodialysis of the
      anaesthetic tetracaine before birth reduced aggressive motor responses towards
      lambs but not protest vocalisations. Similar treatment during the critical period
      for olfactory memory formation and lamb recognition (0-4 h post-partum) had no
      effect on ewes maternal behaviour towards their own lambs. It did, however,
      prevent the normal selective expression of aggressive rejection, and reduced
      protest vocalisation behaviours directed towards strange lambs. These rejection
      behaviours did appear 1 h after the termination of tetracaine infusions despite
      the ewes not being given the opportunity to interact with their own lambs during
      this time. Therefore, tetracaine blockade of the medial frontal cortex prevents
      animals from responding with motor aggression, but not vocal aggression, to odour
      cues from strange lambs, but has no effect on the formation of an olfactory
      recognition memory for their own lambs. Both pre- and post-partum aggressive
      rejection of strange lambs was associated with increased concentrations of
      dopamine, serotonin, glutamate and GABA. When these behaviours were inhibited by
      the tetracaine infusions, extracellular concentrations of these neurotransmitters
      were all increased by the anaesthetic but did not change in response to lambs.
      These findings suggest that a functional medial frontal cortex is not required
      for the formation of an olfactory recognition memory or for mediating pro-active
      maternal behaviours. It is however required for the mediation of motor but not
      vocal aspects of aggressive rejection responses directed towards aversive odour
      cues from strange lambs.

PMID- 12220574
TI  - L- and D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) inhibit
      neurite outgrowth from SH-SY5Y cells.
AB  - Gangliosides and extracellular matrix molecules influence neurite outgrowth, but
      the combinatorial effects of these endogenous agents on outgrowth are unclear.
      Exogenous gangliosides inhibit neurite outgrowth from SH-SY5Y cells stimulated
      with platelet-derived growth factor-BB, and different isoforms of the ceramide
      analog threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) stimulate (L
      PDMP) or inhibit (D-PDMP) glycosphingolipid biosynthesis. In this study, we
      determined whether altering the endogenous ganglioside levels with PDMP in SH
      SY5Y cells regulates neurite outgrowth on the outgrowth-supporting extracellular
      matrix molecule, laminin. In cells stimulated with 20 ng/ml platelet-derived
      growth factor-BB to promote outgrowth, we used image analysis to evaluate neurite
      outgrowth from SH-SY5Y cells grown on endogenous matrix or laminin and exposed to
      L- or D-PDMP. Both L- and D-PDMP decreased neurite initiation (the number of
      neurites/cell, the percent of neurite-bearing cells), elongation (the length of
      the longest neurite/cell, the total neurite length/cell), and branching (the
      number of branch points/neurite) from SH-SY5Y cells on endogenous matrix or
      laminin in a dose-dependent manner in serum-free or serum-containing medium. The
      inhibitory effects of each PDMP isoform were reversible. Inhibition of neurite
      outgrowth by L-PDMP could be mimicked by addition of exogenous gangliosides or C2
      ceramide. Our analyses of neurite outgrowth in SH-SY5Y cells, a model of
      developing or regenerating noradrenergic neurons, demonstrate that increasing or
      decreasing endogenous ganglioside levels decreases neurite outgrowth. These
      results may indicate that SH-SY5Y cells undergo tight regulation by gangliosides,
      possibly through modulation of growth/trophic factor- and/or extracellular matrix
      activated signaling cascades.

PMID- 12220575
TI  - Functional modulation of human brain Nav1.3 sodium channels, expressed in
      mammalian cells, by auxiliary beta 1, beta 2 and beta 3 subunits.
AB  - Voltage-gated sodium channels consist of a pore-forming alpha subunit and two
      auxiliary beta subunits. Excitable cells express multiple alpha subtypes,
      designated Na(v)1.1-Na(v)1.9, and three beta subunits, designated beta1, beta2
      and beta3. Understanding how the different alpha subtypes, in combination with
      the various beta subunits, determine sodium channel behavior is important for
      elucidating the molecular basis of sodium channel functional diversity. In this
      study, we used whole-cell electrophysiological recording to examine the
      properties of the human Na(v)1.3 alpha subtype, stably expressed in Chinese
      hamster ovary cells, and to investigate modulation of Na(v)1.3 function by beta1,
      beta2 and beta3 subunits. In the absence of beta subunits, human Na(v)1.3 formed
      channels that inactivated rapidly (tau(inactivation) approximately equals 0.5 ms
      at 0 mV) and almost completely by the end of 190-ms-long depolarizations. Using
      an intracellular solution with aspartate as the main anion, the midpoint for
      channel activation was approximately -12 mV. The midpoint for inactivation,
      determined using 100-ms conditioning pulses, was approximately -47 mV. The time
      constant for repriming of inactivated channels at -80 mV was approximately 6 ms.
      Coexpression of beta1 or beta3 did not affect inactivation time course or the
      voltage dependence of activation, but shifted the inactivation curve
      approximately 10 mV negative, and slowed the repriming rate ca. three-fold. beta2
      did not affect channel properties, either by itself or in combination with beta1
      or beta3. Na(v)1.3 expression is increased in damaged nociceptive peripheral
      afferents. This change in channel expression levels is correlated with the
      emergence of a rapidly inactivating and rapidly repriming sodium current, which
      has been proposed to contribute to the pathophysiology of neuropathic pain. The
      results of this study support the hypothesis that Na(v)1.3 may mediate this fast
      sodium current.

PMID- 12220576
TI  - The role of extracellular signal-regulated kinase in cognitive and motor deficits
      following experimental traumatic brain injury.
AB  - Traumatic brain injury (TBI) causes neuronal death and alters the plasticity
      (e.g. morphology) of surviving neurons. Both of these events contribute to TBI
      associated neurological deficits, such as memory dysfunction. Although a majority
      of current research is directed towards identifying biochemical cascades
      responsible for cell death, little is known about mechanisms of altered neuronal
      plasticity following TBI. Extracellular signal-regulated kinases (Erk1 and 2)
      play a critical role in growth and have been implicated in long-lasting neuronal
      plasticity and memory storage. The activation of Erk following TBI was
      investigated utilizing an antibody that specifically binds to dually
      phosphorylated Erk. Using this antibody, we report that lateral cortical impact
      injury in rats increases Erk phosphorylation both in the cortex and the
      hippocampus as early as 10 min post-injury. Double immunostaining experiments
      using either a neuron-specific or an astroglial-specific marker show that the
      active Erk is localized almost exclusively in neuronal cells. Furthermore, the
      increase in phospho-Erk immunoreactivity was initially localized to axons and at
      later time points was observed to be predominantly in the cell soma. This
      suggests that Erk redistributed over time and may play a role in retrograde
      signaling. Administration of inhibitors of the Erk cascade worsened retrograde
      amnesia, impaired performances in hippocampus- and amygdala-dependent memory
      tasks, and exacerbated motor deficits following TBI. Furthermore, inhibition of
      this cascade did not have any overt effects on cell survival, but altered
      neuronal morphology as detected by a dendritic-specific marker. These findings
      suggest that the Erk cascade plays an essential role for the maintenance of
      neuronal function and plasticity following TBI.

PMID- 12220577
TI  - Acute administration of phencyclidine induces tonic activation of medial
      prefrontal cortex neurons in freely moving rats.
AB  - Recent studies have reported that acute administration of the psychotomimetic
      drug phencyclidine results in considerable increases in the amounts of both
      extracellular glutamate and dopamine in the medial prefrontal cortex (mPFC).
      However, the effect of phencyclidine on the firing activity of mPFC neurons
      remains unknown. Here, we report the first data on phencyclidine-induced
      activation of mPFC neurons in freely moving rats. Unanesthetized rats received an
      intraperitoneal injection of either phencyclidine (5 mg/kg) or physiological
      saline (0.5 ml/kg) in order to investigate the impulse activity of mPFC neurons
      and behavioral activity. The phencyclidine injection induced a remarkable
      increase (two-fold or more) in the spontaneous discharge rate of the majority of
      mPFC neurons (20/23), and this increase lasted for more than 70 min. In addition,
      a considerable augmentation of behavioral activity was observed that nearly
      paralleled that of the mPFC neuronal activation. In contrast,
      microiontophoretically applied phencyclidine exerted little influence on the
      spontaneous firing activity of most mPFC neurons (25/29) in anesthetized rats,
      although systemically applied phencyclidine produced activation of mPFC neurons
      even under general anesthesia. These results suggest that the behavioral
      abnormalities induced by acute administration of phencyclidine may be caused by
      hyperactivation of mPFC neurons, and that this hyperactivation is elicited
      through excitatory inputs from brain regions outside the mPFC.

PMID- 12220578
TI  - Fos immunoreactivity in rat subcortical visual shell in response to illuminance
      changes.
AB  - Immediate early gene expression has been used frequently as a marker of activity
      in the circadian visual system. Recent evidence suggests that the pretectum
      participates in orchestrating sleep and circadian responses to light. Lesions of
      the pretectum eliminate dark shift-induced rapid eye movement sleep triggering in
      albino rats, and compromise circadian phase shifts in hamsters. We hypothesized
      that regions of the pretectum respond to light with robust and region-specific
      Fos activation, similar to the suprachiasmatic nucleus and intergeniculate
      leaflet. We used Fos expression, the protein product of the immediate early gene
      c-fos, as a functional marker to measure the responses of neurons following acute
      lighting changes. Rats maintained on a 12:12 light-dark cycle were subjected to a
      shift from light-to-dark or from dark-to-light at midday (Zeitgeber time 6) or
      midnight (Zeitgeber time 18). Fos expression was visualized with
      immunocytochemistry and quantified with an automated scoring system. We found
      three regions in the pretectum (the olivary pretectal nucleus, posterior
      limitans, and a region homologous to the hamster commissural pretectal nucleus),
      and two regions in the lateral geniculate complex (the intergeniculate leaflet
      and ventral lateral geniculate nucleus) that demonstrated significant Fos
      activation in response to light. Furthermore, the olivary pretectal nucleus, the
      posterior limitans, and the ventral lateral geniculate nucleus showed
      preferential Fos activation after acute light onset rather than following chronic
      exposure to light at midday, whereas at midnight these nuclei showed Fos
      activation following both chronic light exposure and acute light onset. Given the
      extensive anatomical connections between pretectal nuclei and other nuclei in the
      subcortical visual shell, as well as with centers for sleep and arousal, it is
      highly plausible that these pretectal nuclei integrate information about changes
      in illuminance, and aid in the coordination of acute behavioral responses to
      light.

PMID- 12220579
TI  - BDNF overexpression increases dendrite complexity in hippocampal dentate gyrus.
AB  - There is increasing evidence that brain-derived neurotrophic factor (BDNF)
      modulates synaptic and morphological plasticity in the developing and mature
      nervous system. Plasticity may be modulated partially by BDNF's effects on
      dendritic structure. Utilizing transgenic mice where BDNF overexpression was
      controlled by the beta-actin promoter, we evaluated the effects of long-term
      overexpression of BDNF on the dendritic structure of granule cells in the
      hippocampal dentate gyrus. BDNF transgenic mice provided the opportunity to
      investigate the effects of modestly increased BDNF levels on dendrite structure
      in the complex in vivo environment. While the elevated BDNF levels were
      insufficient to change levels of TrkB receptor isoforms or downstream TrkB
      signaling, they did increase dendrite complexity of dentate granule cells. These
      cells showed an increased number of first order dendrites, of total dendritic
      length and of total number of branch points. These results suggest that dendrite
      structure of granule cells is tightly regulated and is sensitive to modest
      increases in levels of BDNF. This is the first study to evaluate the effects of
      BDNF overexpression on dendrite morphology in the intact hippocampus and extends
      previous in vitro observations that BDNF influences synaptic plasticity by
      increasing complexity of dendritic arbors.

PMID- 12220580
TI  - Localized decrease in serotonin transporter-immunoreactive axons in the
      prefrontal cortex of depressed subjects committing suicide.
AB  - A variety of postmortem brain studies and clinical investigations have provided
      evidence that reduced serotonin neurotransmission is associated with suicidal
      behavior and depression, and several serotonergic parameters have been found to
      be altered in the prefrontal cortex of suicide victims. However, the integrity of
      the serotonin innervation of the prefrontal cortex in mood disorders has not been
      directly investigated. The present study used immunocytochemical methods and an
      antibody against the serotonin transporter to examine the relative density of
      serotonin axons in the dorsolateral prefrontal cortex of suicide victims with a
      diagnosis of major depression. The mean total length of serotonin transporter
      immunoreactive axons per unit area was unchanged in layers 2 and 4 of area 46 in
      the depressed suicide subjects compared to controls, but was significantly (P <
      0.01) decreased by 24% in layer 6 in the depressed suicide group. The total
      length of serotonin transporter-positive axons in layer 6 was reduced in eight of
      the 12 depressed suicide subjects compared to their matched control subjects.
      These findings reveal that depressed subjects who have committed suicide exhibit
      a lamina-specific reduction in a marker of serotonin axons in the dorsolateral
      prefrontal cortex that may reflect an alteration in cortical serotonin
      neurotransmission.

PMID- 12220581
TI  - Testing the Bayesian model of perceived speed.
AB  - In a recent Bayesian model by Weiss, Simoncelli, and Adelson, motion perception
      is biased by a prior favoring slow speeds. This model predicts qualitatively an
      impressive variety of phenomena, including the dependence of perceived speed on
      contrast. We show that the model can also generate quantitative predictions: for
      a drifting grating with contrast c, perceived speed is proportional to c(q)/(k(q)
      + c(q)), with k, q constants. We tested this expression on measurements of
      perceived speed as a function of contrast. Observers indicated the slower of two
      drifting gratings, a test and a standard. For each test contrast we found the
      test speed that appeared to match the standard speed. The model fits the data,
      but only if q is less than 2, the value it would have if the internal
      representation of contrast were linear. The Bayesian model can make correct
      quantitative predictions, but needs to be extended to incorporate a more
      realistic, nonlinear representation of contrast.

PMID- 12220582
TI  - Latency effects in orientation popout.
AB  - A target that differs in orientation from neighboring lines and "pops out" has
      been found to evoke larger responses in cortical V1 cells than lines in the
      uniform texture surround which do not popout (e.g., Journal of Neurophysiology 67
      (1992) 961). If this is more than a coincidence of observations, physiological
      properties of contextual modulation should be reflected in the perception of
      salience. In particular, as the differential suppression from texture surround
      has been reported to be delayed, target salience may be affected by the history
      of surrounding lines, i.e. by their orientation before the target was presented.
      This was tested using a feature flicker paradigm in which target and background
      lines changed their orientations (Experiment 2). All subjects (N = 4) indicated a
      benefit in target detection when target orientation was not previously present in
      the surround. A control experiment showed that this effect was not caused by the
      purely temporal aspects of asynchronous stimulus presentation (Experiment 3). To
      distinguish this effect from other sources of delayed processing, Experiment 1
      compared the performance in target detection and target identification tasks, for
      single-lines and popout targets. All subjects required longer stimulus
      presentation time to identify the orientation of a single line than to detect the
      line itself, indicating that orientation coding needs longer processing than
      encoding stimulus onset. However, most subjects needed even longer presentations
      to detect popout, suggesting that the processing of orientation contrast adds to
      this delay. In an appendix, putative response variations of V1 cells to
      asynchronous flicker are computed.

PMID- 12220583
TI  - Are the original Roelofs effect and the induced Roelofs effect caused by the same
      shift in straight ahead?
AB  - We investigated whether the original Roelofs effect and the induced Roelofs
      effect are caused by the same shift in perceived straight ahead. Subjects were
      presented with a target within a frame in complete darkness. Target and frame
      could both be shifted to the left or right of objective straight ahead. On
      separate trials, subjects gave verbal estimates about the position of either the
      target or the frame. The eccentricity of the frame was underestimated (the
      original Roelofs effect). However, the perceived position of the target did not
      follow this misjudgement of the eccentricity of the frame (the induced Roelofs
      effect was not present). Thus, it is unlikely that both effects have a common
      origin in misjudging egocentric straight ahead.

PMID- 12220584
TI  - An ellipsoidal trajectory model for measuring the line of sight.
AB  - The relationship between the amount of rotation of the eyeball and the amount of
      rotation of the line of sight was investigated. The planar model and ellipsoidal
      model were compared as the trajectory of the center of the pupil. An evaluation
      of precision was carried out by measuring the discrepancy between the direction
      of the target and the estimated direction of the line of sight. The experimental
      results showed that the planar model was more precise than the ellipsoidal model.
      The center of rotation of the eyeball seems to translate along the oblique
      rotation of the eyeball.

PMID- 12220585
TI  - Correlation model for joint development of refined retinotopic map and ocular
      dominance columns.
AB  - We describe a modification to a standard correlation model for the development of
      the geniculocortical projection that relays visual input to the visual cortex.
      The modification is to include threshold-activation of cortical cells as opposed
      to linear activation and it is shown that this can account for topographic map
      refinement (TMR). This contrasts with other models that require cortical cells to
      compete for activation or for neurotrophic support. Simulations are conducted for
      the joint development of ocular dominance columns and TMR in normal animals and
      parameter variations are used to both confirm robustness and to simulate some
      experimental conditions.

PMID- 12220586
TI  - Properties of second-order spatial frequency channels.
AB  - The segregation of texture patterns may be carried out by a set of linear spatial
      filters (to enhance one of the constituent textures), a nonlinearity (to convert
      the higher contrast of response to that constituent to a higher mean response),
      and finally subsequent ("second-order") linear spatial filters (to provide a
      strong response to the texture-defined edge itself). In this paper, the
      properties of such second-order filters are characterized. Observers were
      required to detect or discriminate textures that were modulated between
      predominantly horizontally oriented and predominantly vertically oriented noise
      patterns. Spatial summation for these patterns reached asymptote for a stimulus
      size of 15 x 15 deg. Modulation contrast sensitivity was nearly flat over a five
      octave range of spatial frequency, but was bandpass when stated as efficiency
      (relative to an idealized observer confronted with the same task). Increment
      threshold showed the improved performance with a sub-threshold pedestal seen in
      the "dipper effect", but the typical Weber's law behavior at higher pedestal
      contrasts was not observed at the highest pedestal modulation contrasts
      achievable with our stimuli. Sub-threshold summation experiments indicate that
      second-order filters have a moderate bandwidth.

PMID- 12220588
TI  - A survey of EPA/OPP and open literature on selected pesticide chemicals. III.
      Mutagenicity and carcinogenicity of benomyl and carbendazim.
AB  - The known aneuploidogens, benomyl and its metabolite, carbendazim (methyl 2
      benzimidazole carbamate (MBC)), were selected for the third in a series of
      ongoing projects with selected pesticides. Mutagenicity and carcinogenicity data
      submitted to the US Environmental Protection Agency's (US EPA's) Office of
      Pesticide Programs (OPP) as part of the registration process are examined along
      with data from the open literature. Mutagenicity and carcinogenicity profiles are
      developed to provide a complete overview and to determine whether an association
      can be made between benomyl- and MBC-induced mouse liver tumors and aneuploidy.
      Since aneuploidogens are considered to indirectly affect DNA, the framework
      adopted by the Agency for evaluating any mode of action (MOA) for carcinogenesis
      is applied to the benomyl/MBC data. Both agents displayed consistent, positive
      results for aneuploidy induction but mostly negative results for gene mutations.
      Non-linear dose responses were seen both in vitro and in vivo for aneuploidy
      endpoints. No evidence was found suggesting that an alternative MOA other than
      aneuploidy may be operative. The data show that by 14 days of benomyl treatment,
      events associated with liver toxicity appear to set in motion the sequence of
      actions that leads to neoplasms. Genetic changes (as indicated by spindle
      impairment leading to missegregation of chromosomes, micronucleus induction and
      subsequent aneuploidy in bone marrow cells) can commence within 1-24h after
      dosing, well within the time frame for early key events. Critical steps
      associated with frank tumor formation in the mouse liver include hepatotoxicity,
      increased liver weights, cell proliferation, hypertrophy, and other steps
      involving hepatocellular alteration and eventual progression to neoplasms. The
      analysis, however, reveals weaknesses in the data base for both agents (i.e. no
      studies on mouse tubulin binding, no in vivo assays of aneuploidy on the target
      tissue (liver), and no clear data on cell proliferation relative to dose response
      and time dependency). The deficiencies in defining the MOA for benomyl/MBC
      introduce uncertainties into the analysis; consequently, benomyl/MBC induction of
      aneuploidy cannot be definitively linked to mouse liver carcinogenicity at this
      time.

PMID- 12220589
TI  - Comparative antimutagenic and anticlastogenic effects of green tea and black tea:
      a review.
AB  - Tea is the most popular beverage next to water, consumed by over two-thirds of
      the world's population. It is processed in different ways in different parts of
      the world to give green, black or oolong tea. Experimental studies have
      demonstrated the significant antimutagenic and anticlastogenic effects of both
      green and black tea and its polyphenols in multiple mutational assays. In the
      present review, we have attempted to evaluate and update the comparative
      antimutagenic and anticlastogenic effects of green tea, black tea and their
      polyphenols in different test systems, based on available literature. Existing
      reports have suggested that the protective effects of black tea is as good as
      green tea, however, more studies on black tea and its polyphenols are needed
      before a final conclusion can be made.

PMID- 12220590
TI  - Molecular mechanisms of adaptive response to alkylating agents in Escherichia
      coli and some remarks on O(6)-methylguanine DNA-methyltransferase in other
      organisms.
AB  - Alkylating agents are environmental genotoxic agents with mutagenic and
      carcinogenic potential, however, their properties are also exploited in the
      treatment of malignant diseases. O(6)-Methylguanine is an important adduct formed
      by methylating agents that, if not repaired, can lead to mutations and death. Its
      repair is carried out by O(6)-methylguanine DNA-methyltransferase (MTase) in an
      unique reaction in which methyl groups are transferred to the cysteine acceptor
      site of the protein itself. Exposure of Escherichia coli cells to sublethal
      concentrations of methylating agents triggers the expression of a set of genes,
      which allows the cells to tolerate DNA lesions, and this kind of inducible repair
      is called the adaptive response. The MTase of E. coli, encoded by the ada gene
      was the first MTase to be discovered and one of best characterised. Its repair
      and regulatory mechanisms are understood in considerable detail and this
      bacterial protein played a key role in identification of its counterparts in
      other living organisms. This review summarises the nature of alkylation damage in
      DNA and our current knowledge about the adaptive response in E. coli. I also
      include a brief mention of MTases from other organisms with the emphasis on the
      human MTase, which could play a crucial role in both cancer prevention and cancer
      treatment.

PMID- 12220591
TI  - Methodological issues in pooled analysis of biomarker studies.
AB  - The number of epidemiological studies involving biological markers has
      dramatically increased in the last years. These studies are generally small sized
      and this feature has called attention to the need to summarize the individual
      results, while waiting for the completion of larger studies, designed to answer
      questions that have been raised by preliminary studies. We describe here some of
      the methodological issues related to pooling data of biomarker studies, taking
      advantage of the experience accumulated by conducting two pooled analyses, one of
      studies of metabolic gene polymorphisms and cancer, the other on cytogenetic
      damage. Topics that are considered are: data standardization, population
      selection and bias, statistical analysis, ethical issues. Pooled analysis seems
      to provide a relevant improvement over meta-analysis in molecular epidemiology
      studies, though more research on methodology is needed.

PMID- 12220592
TI  - Use of folic acid and delivery outcome: a prospective registry study.
AB  - Periconceptional use of folic acid is thought to reduce the risk for both neural
      tube defects and other congenital malformations. Most published data were
      obtained retrospectively. We used the Swedish Medical Birth Registry to study
      congenital malformations in infants born of women who reported the use of folic
      acid in early pregnancy (of which 70% probably used it also preconceptionally)
      and compared them with population rates. We divided the material according to two
      major confounders: subfertility problems and use of antiepileptic drugs. We found
      no protective effect of folic acid tablet use on the rate of congenital
      malformations but data on neural tube defects were scarce. Our results support
      the scepticism recently expressed in the literature on the beneficial effect of
      folic acid in preventing congenital malformations, especially of a non-neural
      tube defect type.

PMID- 12220593
TI  - Teratogenicity of the I(Kr)-blocker cisapride: relation to embryonic cardiac
      arrhythmia.
AB  - Cisapride and mosapride are structurally and pharmacologically related prokinetic
      agents. In contrast to mosapride, cisapride causes embryonic lethality in
      teratology studies, and has been related to fatal cardiac arrhythmia in the
      adult. The arrhythmogenic potential of cisapride is linked to its potential to
      inhibit a specific ion channel (I(Kr)) as a side effect. Mosapride lacks I(Kr)
      blocking properties. The aims of this study were (1) to compare the effects of
      cisapride and mosapride on embryonic heart rhythm in vitro and (2) to investigate
      if cisapride in vivo, has potential to induce hypoxia-related teratogenic effects
      as has been shown for selective I(Kr)-blockers. Cisapride induced severe
      embryonic bradycardia (approximately 60% decrease), and arrhythmia in 94% of the
      cultured rat embryos at 1000 ng/ml. Mosapride did not induce any bradycardia or
      arrhythmia up to 2000 ng/ml. In vivo, single dose administration of cisapride to
      rats on gestational day (GD) 13 caused digital reductions (8/108 fetuses, 4/9
      litters) at 75 mg/kg and high incidence of embryonic death (55-82%) at 100-200
      mg/kg. Identical developmental toxic effects have been described after temporary
      interruption of oxygen supply, and after single dose administration of selective
      I(Kr)-blockers, on the same GD. The results support the idea that all potent
      I(Kr)-blocking agents have the potential to cause embryolethality and
      teratogenicity, and that the adverse effects are mediated via hypoxic episodes
      due to embryonic arrhythmia.

PMID- 12220594
TI  - Effects of lead (Pb) exposure during gestation and lactation on female pubertal
      development in the rat.
AB  - Lead (Pb) can delay sexual maturation; however, the mechanism and critical time
      of insult are not clearly defined. Therefore, we assessed maternal Pb levels
      during low-level gestational and/or lactational exposure, as well as blood and
      tissue Pb in developing fetuses in relation to the subsequent detrimental effects
      of Pb on puberty-related hormones and the onset of female puberty. Adult Fisher
      344 female rats were gavaged daily with either a 1-ml solution of PbAc containing
      12 mg/ml Pb or an equal volume of sodium acetate (NaCl), for the controls, from
      30 days prior to breeding until their pups were weaned at 21 days. By cross
      fostering at the time of birth, the pups were either exposed to PbAc or NaAc
      during gestation only, lactation only, or during both gestation and lactation. Pb
      delayed the timing of puberty and this delay was associated with suppressed serum
      levels of insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), and
      estradiol (E(2)). Liver IGF-1 mRNA was not affected, suggesting that Pb altered
      translation and/or secretion of IGF-1. We reported previously that peripherally
      derived IGF-1 acts at the hypothalamic level to facilitate LH release at puberty;
      hence, we suggest that the action of Pb in decreasing circulating IGF-1
      contributes to the delayed puberty. The detrimental effects occurred regardless
      of the developmental time of exposure, although gestational exposure appeared
      more sensitive to the effects of Pb. Also, the effects noted were with blood Pb
      levels less than previously reported and these levels are relevant to human
      health concerns.

PMID- 12220595
TI  - The perinatal and postnatal toxicity of D-methylphenidate and D,L-methylphenidate
      in rats.
AB  - D-methylphenidate is an enantiomer of D,L-methylphenidate and was developed as an
      improved treatment for attention deficit hyperactivity disorder (ADHD) in
      children. The current study was performed to assess the potential perinatal and
      postnatal toxicity of both compounds in rats. About 125 presumed pregnant rats
      were assigned to five dose groups of 25 each. They were dosed with 2, 6, and 20
      mg/kg/day D-methylphenidate and 40 mg/kg/day D,L-methylphenidate from gestation
      Day 7 to lactation Day 20. F1 generation rats were rebred to produce F2 fetuses.
      Various perinatal and postnatal measurements were made for the F0 and F1 rats.
      Among the significant findings were a reduction in maternal body weight gain for
      20 mg/kg/day D-methylphenidate and D,L-methylphenidate and increased incidences
      of dilated pupil and vocalization for D,L-methylphenidate during the gestation
      period. Neither compound produced any other significant adverse findings in F0
      and F1 generation rats at doses that were at least 25 times the maximum daily
      human therapeutic dose.

PMID- 12220596
TI  - Effect of gonadotropin-releasing hormone antagonist on ovarian and uterine
      weights in immature female rats.
AB  - The immature rat uterotrophic assay has been proposed as a screening test method
      for detecting estrogenic and antiestrogenic chemicals. Although the immature rat
      uterotrophic assay is advantageous because the test animals are not traumatized
      by the ovariectomizing process, the effect of endogenous estrogen on ovarian and
      uterine weight in the immature animals that are used in immature rat uterotrophic
      assay has not received much attention. In this study, 19-day-old rats were
      treated with antide, a gonadotropin-releasing hormone antagonist, antide, to
      block gonadal production of endogenous estrogen. Uterine and ovarian weights of
      the antide-treated animals were markedly lower than those of control animals.
      This finding suggests that endogenous gonadal estrogen may already be acting on
      the uterus and ovaries in immature rats. Blocking endogenous estrogen with a
      gonadotropin-releasing hormone antagonist may enhance the sensitivity of the
      immature rat uterotrophic assay; however, the possibility that this protocol may
      interfere with the ability of the immature rat uterotrophic assay to detect
      centrally-mediated effects can not be discounted.

PMID- 12220597
TI  - Influence of cadmium exposure on in vitro ovine gamete dysfunction.
AB  - This study was conducted to determine the in vitro effects of three different
      cadmium concentrations (0, 2, and 20 microM CdCl(2)) on oocyte maturation,
      fertilisation, and acrosome integrity and sperm viability in sheep. Cumulus
      oocyte complexes were recovered from ovaries of slaughtered sheep and sperm were
      collected by artificial vagina from adult rams. The oocyte maturation rate was
      significantly affected (P < 0.001) by Cd at both concentrations, with a metaphase
      II (MII) rate of 96.8, 63.8, and 32.0% for 0, 2, and 20 microM cadmium,
      respectively. In the second experiment, the presence of Cd significantly
      decreased (P < 0.01) the rate of oocytes resting in MII after 24-h postmaturation
      culture, compared with the control group (93.8 versus 29.0 and 19.8%,
      respectively, for 0, 2, and 20 microM Cd). Oocytes cultured with Cd 2 microM
      showed a higher activation rate (59.5%, P < 0.001) with one or two pronucleus
      than with 0 and 20 microM Cd (6.2 and 22.9%, respectively). During fertilisation
      the presence of fertilised oocytes was decreased in both culture systems with Cd
      compared with the control (76.1, 25.9, and 4.7% for 0, 2, and 20 microM Cd,
      respectively; P < 0.001) while polyspermy was increased in the 2 microM Cd group
      (23.5 for 2 microM versus 6.7 and 0%, respectively, for 0 and 20 microM groups).
      In both experiments Cd significantly increased (P < 0.001) the rates of oocyte
      degeneration. In the third experiment, Cd 20 microM significantly decreased (P <
      0.01) the viability rate (35.6%) of spermatozoa compared with 2 microM (57.6%)
      and 0 microM (54.4%) while Cd 2 microM increased (P < 0.01) acrosome-reacted
      spermatozoa (45.2%) compared with 20 microM (32.5%) and control (31.9%). The
      results suggest that in vitro cadmium at the lowest dose tested affects the
      physiological function of both ovine gametes but at higher dose tested can
      compromise cell viability.

PMID- 12220598
TI  - 2-Bromopropane induces DNA damage, impairs functional antioxidant cellular
      defenses, and enhances the lipid peroxidation process in primary cultures of rat
      Leydig cells.
AB  - Utilization of highly enriched preparations of steroidogenic Leydig cells has
      proven invaluable for studying the direct effects of various hormones and agents
      on Leydig cell function in vitro. It is widely reported that male reproductive
      organs are particularly susceptible to the deleterious effects of reactive oxygen
      species (ROS) and lipid peroxidation, which ultimately lead to impaired
      fertility. The purpose of the study was to examine the potential of 2
      bromopropane (2-BP) to induce oxidative stress and antioxidant function in
      primary cultures of rat Leydig cells. Leydig cells were isolated from the testes
      of Sprague-Dawley rats. The purity of Leydig cells was determined to be 94.6% and
      the cells maintained their testosterone secreting capabilities for 48 h. Fresh
      medium containing 2-BP (1.00, 0.10, 0.01 mM, and vehicle control) and 1 U human
      chorionic gonadotropin (hCG) were added in the cell culture. Superoxide dismutase
      (SOD) activity, malondialdehyde (MDA), and glutathione peroxidase (GSH-PX) were
      analyzed in the medium of each well by biochemical methods. Additionally, DNA
      damage was examined using the Comet assay. The proportion of cells with undamaged
      DNA was decreased significantly and those with different grades of damaged DNA
      were increased significantly in the cells exposed to 2-BP. The level of MDA and
      GSH-PX activity increased significantly in the cell groups exposed to 0.10 and
      1.00 mM 2-BP, whereas, SOD activity decreased considerably in these two groups of
      cells when compared to the control. The data indicate that 2-BP induces DNA
      damage, impairs functional antioxidant cellular defenses, and enhances the lipid
      peroxidation in cultured Leydig cells. These effects may be responsible for the
      testicular toxicity noted in laboratory animals and humans.

PMID- 12220599
TI  - Testicular toxicity in sodium fluoride treated rats: association with oxidative
      stress.
AB  - This study examined the effect of sodium fluoride, a water pollutant important
      through the world, including India, on testicular steroidogenic and gametogenic
      activities in relation to testicular oxidative stress in rats. Sodium fluoride
      treatment at 20mg/kg/day for 29 days by oral gavage resulted in significant
      diminution in the relative wet weight of the testis, prostate, and seminal
      vesicle without alteration in the body weight gain. Testicular delta(5),3beta
      hydroxysteroid dehydrogenase (HSD) and 17beta-HSD activities were decreased
      significantly along with significant diminution in plasma levels of testosterone
      in the fluoride-exposed group compared to the control. Epididymal sperm count was
      decreased significantly in the fluoride-treated group and qualitative examination
      of testicular sections revealed fewer mature luminal spermatozoa in comparison to
      the control. The seminiferous tubules were dilated in treated animals. Fluoride
      treatment was associated with oxidative stress as indicated by an increased level
      of conjugated dienes in the testis, epididymis, and epididymal sperm pellet with
      respect to control. Peroxidase and catalase activities in the sperm pellet were
      decreased significantly in comparison to the control. The results of this
      experiment indicate that fluoride at a dose encountered in drinking water in
      contaminated areas exerts an adverse effect on the male reproductive system and
      this effect is associated with indicators of oxidative stress.

PMID- 12220602
TI  - Putting drug abuse research to use in real-life settings.

PMID- 12220603
TI  - Standing at the crossroads.

PMID- 12220604
TI  - MET meets the real world: design issues and clinical strategies in the Clinical
      Trials Network.
AB  - The Clinical Trials Network (CTN) represents a major initiative intended to
      bridge the gap between research and practice in substance abuse treatment by
      implementing a range of studies evaluating behavioral, pharmacologic, and
      combined treatments in community-based drug abuse treatment programs across the
      country. This article describes the development of CTN protocols evaluating the
      effectiveness of Motivational Enhancement Therapy and Motivational Interviewing.
      Design, training, and implementation challenges associated with conducting a
      clinical trial of brief behavioral treatments in community programs are
      discussed. Issues requiring attention included the diversity in treatments
      offered across sites, heterogeneity in the study sample, and training of
      clinicians drawn from the staff of community programs to deliver the study
      treatments.

PMID- 12220605
TI  - Recent advances in the dissemination of contingency management techniques:
      clinical and research perspectives.
AB  - Research studies have demonstrated the efficacy of contingency management
      procedures in treating substance use disorders. However, these procedures have
      only recently been adapted to and tested within community-based clinical
      settings. This article reviews recent advances in the field of contingency
      management, with attention to dissemination issues. Counselor's reactions to the
      implementation of these techniques in individual and group treatment modalities
      are detailed. Suggestions are made for areas in which more research is needed,
      from both a counselor's and researcher's perspective.

PMID- 12220606
TI  - Buprenorphine: blending practice and research.
AB  - Although pharmacotherapy has been a mainstay in opiate addiction, not much
      research in the development of new opiate medications has been translated into
      clinical practice. In part, this is because opiate pharmacotherapy has not been
      an integral element of mainstream medical practice and because new medications
      developed by research are not available to clinicians. All that will change with
      the availability of buprenorphine for addiction treatment. For the first time in
      nearly a century, clinicians will be able to treat opiate addicts in the general
      medical setting, in the same manner they treat other patients. The unique
      pharmacological properties of buprenorphine, with its high patient acceptance,
      favorable safety profile, and ease of clinical administration, should facilitate
      its clinical integration. However, successful implementation will require changes
      in the understanding and attitude of clinicians, policymakers, and society.

PMID- 12220607
TI  - History and current status of opioid maintenance treatments: blending conference
      session.
AB  - Opiate addiction is a chronic, relapsing disorder. Left untreated, high morbidity
      and mortality rates are seen. Pharmacotherapies for this disorder using mu opiate
      agonists (methadone and levomethadyl acetate) and partial agonists have been
      developed in the last 40 years. Agonist pharmacotherapy with oral methadone for
      the treatment of opiate dependence was developed in clinical pharmacology studies
      at Rockefeller University by Dole, Nyswander, and Kreek. Further studies by this
      laboratory and others established that moderate to high dose treatment with
      methadone (80-120 mg) reduced or eliminated opiate use in outpatient settings
      with consequent reductions in morbidity and up to 4-fold reductions in mortality.
      Levomethadyl acetate (LAAM), a congener of methadone, is biotransformed to active
      metabolites responsible for its longer duration of action. The Federal
      Regulations regarding the dispensation of methadone and LAAM have recently been
      revised to facilitate the treatment of patients under a "medical maintenance"
      model. Future regulatory reform will likely involve the establishment of rules
      for "office based opioid treatment."

PMID- 12220608
TI  - Incorporating brain research findings into standard treatment: an example using
      the Matrix Model.
AB  - One way to promote the goal of broadening the application of research to applied
      treatment is through the development and dissemination of empirically supported
      clinical treatment manuals. NIDA and NIAAA have published a series of manuals
      that delineate specific psychotherapies and/or behavioral approaches designed for
      the treatment of drug and alcohol abuse. This article describes a manualized
      treatment approach, the Matrix Model, which incorporates several of these
      psychosocial interventions with some basic explanations of recent brain research
      to form a comprehensive, multi-component model of outpatient stimulant abuse
      treatment. A large multi-site trial sponsored by CSAT compares the Matrix Model
      of outpatient treatment with treatment as usual in 7 sites where methamphetamine
      is a significant problem. The translation and adaptation of the Matrix manual for
      cocaine users in Mexico and methamphetamine users in Thailand will offer
      opportunities to evaluate this approach with very diverse populations of
      stimulant users.

PMID- 12220609
TI  - Improving service delivery to the dually diagnosed in Los Angeles County.
AB  - Service delivery to dually diagnosed individuals remains problematic in many
      communities because of entrenched administrative structures that maintain the
      separation of mental health and substance abuse treatment systems. This article
      describes efforts to improve service delivery to dually diagnosed individuals in
      Los Angeles County by increasing communication, coordination, and collaboration
      across the two treatment systems. Findings are presented on the relationships
      among program models of service delivery, treatment orientations of programs, and
      interactions with other service providers to the dually diagnosed. Results showed
      that drug treatment programs that adhered more closely to an integrated model of
      service delivery received more patient referrals from case management outreach
      teams and that programs with a stronger counseling approach to treatment had more
      linkages with other service providers. Knowledge gained from research on these
      differing models of service delivery can be combined with new clinical advances
      to improve service delivery to the dually diagnosed.

PMID- 12220610
TI  - Bridging the research-practice gap in adolescent substance abuse treatment: the
      case of brief strategic family therapy.
AB  - This article presents an empirically validated intervention, Brief Strategic
      Family Therapy (BSFT), for the treatment of adolescent drug abusers. The BSFT
      intervention steps and program format are presented. Challenges to implementation
      in community treatment settings are discussed to identify factors that may
      facilitate or block the integration of BSFT into community practice settings. In
      particular, this discussion explores how 3 critical aspects of community
      treatment programs--program philosophy, program structure, and cost/funding-
      influence the blending of BSFT into community treatment practice.

PMID- 12220611
TI  - Effects of women-sensitive, long-term residential treatment on psychological
      functioning of diverse populations of women.
AB  - A number of studies have found that women who abuse substances enter treatment
      with greater psychological problems and more vulnerabilities than men. This
      article reports on a 5-year study of clients in a comprehensive, residential drug
      treatment program for women and their children. Psychological assessments on 362
      women included the Basic Personality Inventory (BPI), the Center for
      Epidemiologic Studies Depression Scale (CES-D), and the Luria-Nebraska
      Neuropsychological Battery, Screening Test (LNNB-ST). Early in the course of
      treatment, the typical client tends to experience a great deal of distress, as
      evidenced by scores on the CES-D. Other assessments indicate she is relatively
      alienated, mistrustful of others, and resentful of rules imposed on her by
      others. Repeated assessments show that these psychological indicators improve
      significantly as the client progresses through the treatment program. Additional
      studies are needed to focus on long-term treatment outcomes of women in programs
      designed specifically for them.

PMID- 12220612
TI  - Treatment of methamphetamine use disorders: an update.
AB  - Methamphetamine (MA) is a major public health and criminal justice problem in
      much of the Western and Midwestern US, and its use seems to be increasing east of
      the Mississippi River. MA use can produce significant psychiatric and medical
      consequences, including psychosis, dependence, overdose, and death. Cognitive
      behavioral therapy and contingency management are among the most promising
      approaches for treatment of MA abuse and dependence. A multisite study evaluating
      the Matrix Model of outpatient treatment will soon be completed to provide data
      on this manualized approach. An ambitious program of pharmacotherapy development
      research is currently being sponsored by the National Institute on Drug Abuse
      (NIDA) in geographic areas significantly affected by MA use. The development of
      treatments for MA-related problems is particularly critical for a number of user
      groups including MA users who experience persistent psychosis, pregnant women and
      women with children, gay and bisexual men, and MA users involved in the criminal
      justice system.

PMID- 12220613
TI  - The effects and consequences of selected club drugs.
AB  - Ecstasy (MDMA), gamma-hydroxybutyrate (GHB), ketamine, and methamphetamine are 4
      examples of club drugs that are increasing in popularity. Although the
      pharmacological classifications of these drugs vary, MDMA has structural
      similarities to both amphetamine and the hallucinogen mescaline. Ketamine and GHB
      are anesthetic agents and methamphetamine is a long-acting psychostimulant.
      Medical visits for club drug-related toxicity have sharply increased across the
      country. This article provides a brief review of the literature on club drugs.

PMID- 12220614
TI  - A successful researcher-practitioner collaboration in substance abuse treatment.
AB  - The best efforts to improve substance abuse treatment come from the integration
      of practice and research. The purpose of this article is to discuss factors that
      contribute to fruitful research-practice collaborations using the example of our
      recent successful partnership between a group of treatment researchers and a
      group of substance abuse recovery houses operated by Fresh Start. The research
      effort was the Drug Evaluation Network System, a computer assisted method of
      integrating clinical research and policy relevant information into a standard
      admission interview. The article discusses several factors that were important in
      integrating this research effort into the treatment system. These factors
      included adequate advance preparation of clinical and research staff to employ
      the new system, overcoming bilateral biases, and determining the degree to which
      the clinicians' and researchers' missions are matched. The paper also discusses a
      range of general factors to consider in implementing and maintaining successful
      research-to-practice integrations.

PMID- 12220615
TI  - Antioxidant and prooxidant mechanisms in the regulation of redox(y)-sensitive
      transcription factors.
AB  - A progressive rise of oxidative stress due to the altered reduction-oxidation
      (redox) homeostasis appears to be one of the hallmarks of the processes that
      regulate gene transcription in physiology and pathophysiology. Reactive oxygen
      (ROS) and nitrogen (RNS) species serve as signaling messengers for the evolution
      and perpetuation of the inflammatory process that is often associated with the
      condition of oxidative stress, which involves genetic regulation. Changes in the
      pattern of gene expression through ROS/RNS-sensitive regulatory transcription
      factors are crucial components of the machinery that determines cellular
      responses to oxidative/redox conditions. Transcription factors that are directly
      influenced by reactive species and pro-inflammatory signals include nuclear
      factor-kappaB (NF-kappaB) and hypoxia-inducible factor-1alpha (HIF-1alpha). Here,
      I describe the basic components of the intracellular oxidative/redox control
      machinery and its crucial regulation of oxygen- and redox-sensitive transcription
      factors such as NF-kappaB and HIF-1alpha.

PMID- 12220616
TI  - Interleukin-1beta-induced cyclooxygenase-2 expression is mediated through
      activation of p42/44 and p38 MAPKS, and NF-kappaB pathways in canine tracheal
      smooth muscle cells.
AB  - Interleukin-beta (IL-1beta) was found to induce inflammatory responses in the
      airways, which exerted a potent stimulus for PG synthesis. This study was to
      determine the mechanisms of IL-1beta-enhanced cyclooxygenase (COX)-2 expression
      associated with PGE(2) synthesis in tracheal smooth muscle cells (TSMCs). IL
      1beta markedly increased COX-2 expression and PGE(2) formation in a time- and
      concentration-dependent manner in TSMCs. Both COX-2 expression and PGE(2)
      formation in response to IL-1beta were attenuated by a tyrosine kinase inhibitor,
      genistein, a phosphatidylcholine-phospholipase C inhibitor, D609, a
      phosphatidylinositol-phospholipase C inhibitor, U73122, protein kinase C
      inhibitors, GF109203X and staurosporine, removal of Ca(2+) by addition of
      BAPTA/AM plus EGTA, and phosphatidylinositol 3-kinase (PI3-K) inhibitors,
      LY294002 and wortmannin. IL-1beta-induced activation of NF-kappaB correlated with
      the degradation of IkappaB-alpha in TSMCs. IL-1beta-induced NF-kappaB activation,
      COX-2 expression, and PGE(2) synthesis were inhibited by the dominant negative
      mutants of NIK and IKK-alpha, but not by IKK-beta. IL-1beta-induced COX-2
      expression and PGE(2) synthesis were completely inhibited by PD98059 (an
      inhibitor of MEK1/2) and SB203580 (an inhibitor of p38 inhibitor), but these two
      inhibitors had no effect on IL-1beta-induced NF-kappaB activation, indicating
      that activation of p42/44 and p38 MAPK and NF-kappaB signalling pathways were
      independently required for these responses. These findings suggest that the
      increased expression of COX-2 correlates with the release of PGE(2) from IL-1beta
      challenged TSMCs, at least in part, independently mediated through MAPKs and NF
      kappaB signalling pathways in canine TSMCs. IL-1beta-mediated responses were
      modulated by PLC, Ca(2+), PKC, tyrosine kinase, and PI3-K in these cells.

PMID- 12220617
TI  - Substance P-induced activation of p42/44 mitogen-activated protein kinase
      associated with cell proliferation in human tracheal smooth muscle cells.
AB  - Substance P (SP) released from sensory nerve endings in the airways induces
      several responses including cell proliferation. However, the mechanisms were not
      completely understood in tracheal smooth muscle cells (TSMCs). We therefore
      investigated the effect of SP on cell proliferation and activation of p42/p44
      mitogen-activated protein kinase (MAPK) in these cells. SP stimulated
      [3H]thymidine incorporation and p42/p44 MAPK phosphorylation in a time- and
      concentration-dependent manner in TSMCs. Both DNA synthesis and phosphorylation
      of MAPK in response to SP were attenuated by pretreatment with pertussis toxin,
      genistein, D609, U73122, staurosporine, removal of Ca(2+) by BAPTA/AM plus EGTA,
      PD98059, and SB202190. Furthermore, overexpression of dominant negative mutants,
      H-Ras-15A and Raf-N4, significantly suppressed p42/p44 MAPK activation induced by
      SP and PDGF-BB. These results conclude that the mitogenic effect of SP was
      mediated through the activation of Ras/Raf/MEK/MAPK pathway, which was modulated
      by PC-PLC, PI-PLC, Ca(2+), and PKC in cultured human TSMCs.

PMID- 12220618
TI  - C(2)-ceramide-induced circular smooth muscle cell contraction involves PKC
      epsilon and p44/p42 MAPK activation in cat oesophagus. Mitogen-activated protein
      kinase.
AB  - We investigated the mechanism of C(2)-ceramide (C(2))-induced circular smooth
      muscle cell contraction in cat oesophagus. C(2) produced contraction of smooth
      muscle cells isolated by enzymatic digestion, peaked at 30 s and was sustained at
      a plateau at 5 min. The response to C(2) was concentration-dependent. H-7 or
      chelerythrine inhibited C(2)-induced contraction, while the diacylglycerol (DAG)
      kinase inhibitor, R59949, had no effect, suggesting that the contraction is
      protein kinase C (PKC) pathway-dependent. To test if PKC-mediated contraction may
      be isozyme-specific, we examined the effects of PKC isozymes antibodies on
      contraction. PKC-epsilon antibody inhibited the contraction by C(2) but not by
      PKC-betaII or -gamma, suggesting that PKC-epsilon mediates the contraction by
      C(2). To characterize the specific PKC isozymes that mediate contraction of the
      smooth muscle cells, we used, as an inhibitor, N-myristoylated peptides (myr-PKC)
      derived from the pseudosubstrate sequences of PKC-(alpha)(beta)(gamma), -alpha, 
      delta, or -epsilon. myr-PKC-epsilon only inhibited the contraction, which was
      concentration-dependent, suggesting that PKC-epsilon isozyme is involved in the
      contraction. To examine which mitogen-activated protein kinases (MAPKs) are
      involved in C(2)-induced contraction, specific MAPK inhibitors (MEK inhibitor,
      PD98059, and p38 MAPK inhibitor, SB202190) are used. Preincubation of PD98059
      blocked the contraction induced by C(2) in a concentration-dependent manner.
      However, SB202190 had no effects on contraction. C(2) increased the intensity of
      the bands identified by phosphospecific p44/p42 MAPK antibody and preincubation
      of PD98059 decreased the intensity of bands as compared with C(2)-stimulated
      cells. In conclusion, C(2) produced the contraction of smooth muscle cells of cat
      oesophagus. The contraction is mediated by PKC-epsilon, resulting in the
      activation of p44/p42 MAPK.

PMID- 12220619
TI  - CD157 undergoes ligand-independent dimerization and colocalizes with caveolin in
      CHO and MCA102 fibroblasts.
AB  - CD157, a glycosylphosphatidylinositol (GPI)-anchored glycoprotein, has recently
      been shown to induce protein tyrosine phosphorylation in monocytes differentiated
      from HL-60 cells (mHL-60) in a ligand-dependent manner, but in a ligand
      independent manner in stable CD157-transfected CHO (CHO/CD157) and MCA102
      (MCA/CD157) fibroblasts [Cell Signal. 11 (1999) 891-897.]. Many GPI-anchored
      proteins need to be clustered by their ligands or antibodies to induce
      redistribution to caveolae and a concomitant activation of the associated signal
      transducing proteins [Nature 387 (1997) 569-572.]. Here, we demonstrate that
      CD157, independent of antibody crosslinking, undergoes dimerization with
      disulfide bond formation and localization in caveolae in CHO/CD157 and MCA/CD157
      fibroblasts. However, the native CD157 induced in mHL-60 cells remains a monomer
      form. The structural integrity of caveolae is required for the association of
      CD157 with caveolin and CD157-mediated tyrosine kinase signalling in the
      fibroblasts. We propose that an overexpression of CD157 could lead to its
      dimerization and relocation to caveolae and to further result in the initiation
      of signalling processes.

PMID- 12220620
TI  - Sphingosine 1-phosphate is a ligand of the human gpr3, gpr6 and gpr12 family of
      constitutively active G protein-coupled receptors.
AB  - Five G protein-coupled receptors (GPCRs) for the lysophospholipid sphingosine 1
      phosphate (S1P) have been cloned and characterized so far. We report here about
      the identification of gpr3, gpr6 and gpr12 as additional members of the S1P-GPCR
      family. When expressed transiently in HEK293 cells, gpr3, gpr6 and gpr12 confer
      constitutive activation of adenylate cyclase (AC) similar in amplitude to that
      seen with fully activated G(alpha)(s)-coupled receptors. Culturing the
      transfected cells in medium with charcoal-stripped serum (devoid of lipids)
      significantly reduces cyclic adenosine monophosphate (cAMP) levels, suggesting a
      lipid-like ligand. A library containing 200 bioactive lipids was applied in
      functional assays recording intracellular Ca(2+) mobilization. S1P and
      dihydrosphingosine 1-phosphate (DHS1P) were identified as functional activators
      exhibiting nanomolar EC(50) values. In the presence of the S1P and LPA receptor
      antagonist suramin, gpr3-, gpr6- and gpr12-mediated intracellular Ca(2+)
      mobilization via S1P is enhanced. Besides constitutive activation of G(alpha)(s)
      type of G proteins, all three receptors are capable of constitutively activating
      inhibitory G(alpha)(i/o) proteins: (i) in the presence of pertussis toxin, gpr3-,
      gpr6- and gpr12-mediated stimulation of AC is enhanced; and (ii) overexpression
      of G(alpha)(i) significantly reduces the stimulatory action on intracellular cAMP
      levels. Agonist (S1P)-mediated internalization can be visualized in intact HEK293
      cells using a gpr6 green fluorescent protein (GFP) fusion protein. In summary,
      our data suggest that gpr3, gpr6 and gpr12 are a family of constitutively active
      receptors with dual coupling to G(alpha)(s) and G(alpha)(i) type of G proteins.
      Constitutive activation of AC and mobilization of [Ca(2+)](i) can be modulated by
      the sphingophospholipids S1P and DHS1P, adding three additional members to the
      family of S1P receptors.

PMID- 12220621
TI  - Inhibition of the type 1 inositol 1,4,5-trisphosphate receptor by 2
      aminoethoxydiphenylborate.
AB  - 2-Aminoethoxydiphenylborate (2-APB) inhibits the extent of inositol 1,4,5
      trisphosphate (InsP(3))-induced Ca(2+) release from cerebellar microsomes with a
      potency that is dependent upon the InsP(3) concentration used. At high InsP(3)
      concentrations (10 microM), the concentration of 2-APB required to cause half
      maximal InsP(3)-induced Ca(2+) release (IC(50)) was greater than 1 mM, while at
      0.25 microM InsP(3) this reduced to 220 microM. The fact that the inhibition of
      the extent of InsP(3)-induced Ca(2+) release (IICR) by 2-APB was not restored to
      control levels by high concentrations of InsP(3), in addition to the fact 2-APB
      did not substantially inhibit [3H]InsP(3) binding to its receptor, indicates that
      the inhibition is not competitive in nature. Since the cooperativity of IICR as a
      function of InsP(3) was reduced in the presence of 2-APB (Hill coefficient
      changing from 1.9 in the absence of 2-APB to 1.4 in the presence of 1 mM 2-APB),
      this suggests that it is acting as an allosteric inhibitor. 2-APB also reduces
      the rate constants for IICR. In cerebellar microsomes this release process is
      biphasic in nature, with a fast and slow phase. 2-APB appears particularly to
      affect the fast-phase component. Although 2-APB does not inhibit the ryanodine
      receptor, it does inhibit the Ca(2+) ATPase activity as well store-operated
      Ca(2+) entry channels, which may limit its use as a specific membrane permeant
      InsP(3) receptor inhibitor.

PMID- 12220622
TI  - Modulation of caspase activation and p27(Kip1) degradation in the p53-induced
      apoptosis in IW32 erythroleukemia cells.
AB  - To examine the p53-mediated biological activities and signalling pathways, we
      generated stable transfectants of the p53-null IW32 murine erythroleukemia cells
      expressing the temperature-sensitive p53 mutant DNA, tsp53(val135). Two clones
      with different levels of p53 protein expression were selected for further
      characterization. At permissive temperature, clone 1-5 cells differentiated along
      the erythroid pathway, and clone 3-2 cells that produced greater levels (3.5
      fold) of p53 underwent apoptosis. Apoptosis of 3-2 cells was accompanied by
      mitochondrial cytochrome c release and caspase activation as well as by cleavage
      of caspase substrates. Bax protein was induced to a similar extent in these
      clones by wild-type p53; expression of p21(Cip1/Waf1) and p27(Kip1) proteins was
      also increased. However, significantly lesser extent of induction for both CDK
      inhibitors was detected in the apoptotic 3-2 clone. The general caspase inhibitor
      benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD.fmk) blocked the p53
      induced apoptosis in 3-2 cells, with a concomitant elevation of p27(Kip1),
      suggesting that p27(Kip1) protein underwent caspase-dependent proteolysis in the
      apoptotic 3-2 cells. Together these results linked a pathway involving cytochrome
      c release, caspase activation and p27(Kip1) degradation to the p53-induced
      apoptosis in IW32 erythroleukemia cells.

PMID- 12220623
TI  - Molecular evolution from abiotic scratch.
AB  - Recent papers on the emerging new theory of protein evolution are reviewed.
      Reconstruction of codon chronology, analysis of loop fold structure of proteins,
      and quantitative correspondence between optimal DNA ring closure size and protein
      domain size allow to outline specific stages in early protein evolution, each
      with its own size range.

PMID- 12220624
TI  - The physiological role of dehydroascorbic acid.
AB  - Dehydroascorbic acid (DHA) is abundant in the human diet and also is generated
      from vitamin C (ascorbic acid, AA) in the lumen of the gastrointestinal tract.
      DHA is absorbed from the lumen of the small intestine and reduced to AA, which
      subsequently circulates in the blood. Utilization of AA as an antioxidant and
      enzyme cofactor causes its oxidation to DHA in extracellular fluid and cells. DHA
      has an important role in many cell types because it can be used to regenerate AA.
      Both physiological (e.g. insulin, insulin-like growth factor I, cyclic AMP) and
      pathological (e.g. oxidative stress, diabetes, sepsis) factors alter the
      transport and metabolic mechanisms responsible for this DHA recycling.

PMID- 12220625
TI  - Telomere maintenance in telomerase-positive human ovarian SKOV-3 cells cannot be
      retarded by complete inhibition of telomerase.
AB  - The two known mechanisms for telomere maintenance in eukaryocytes are telomerase
      in telomerase-positive cells and alternative lengthening of telomeres (ALT) in
      telomerase-negative cells. We report here that telomere maintenance in the
      telomerase-positive human ovarian SKOV-3 cells was not affected by inhibition of
      telomerase. For comparison, the effect of telomerase inhibitors on telomere
      maintenance in another telomerase-positive cell line (i.e. human pharynx FaDu
      cells) and the telomerase-negative human osteosarcoma Saos-2 cells was examined.
      Telomerase activity was measured using a modified telomeric repeat amplification
      protocol and telomere length was measured using a solution hybridization-based
      method and fluorescence in situ hybridization. A reverse transcriptase inhibitor
      (3'-azido-deoxythymidine or AZT) and an antisense against a component of human
      telomerase RNA (antisense hTR) were used to inhibit telomerase. FaDu and SKOV-3
      cells showed comparable baseline telomerase activity. Telomerase activity in both
      cells was inhibited about equally by AZT (maximal inhibition of approximately
      80%) and by expression of antisense hTR (complete inhibition in SKOV-3 cells and
      maximal inhibition of approximately 80% in FaDu cells). However, treatment with
      telomerase inhibitors resulted in approximately 50% telomere shortening in FaDu
      cells but had no effect on SKOV-3 nor Saos-2 cells. SKOV-3 cells did not show the
      characteristic features of ALT (i.e. heterogeneous telomere length and
      promyelocytic leukemia bodies), whereas these ALT features were observed in Saos
      2 cells. Collectively, these results suggest the existence of a telomerase
      independent mechanism of telomere maintenance in the telomerase-positive SKOV-3
      cells.

PMID- 12220626
TI  - Association of the mammalian proto-oncoprotein Int-6 with the three protein
      complexes eIF3, COP9 signalosome and 26S proteasome.
AB  - The mammalian Int-6 protein has been characterized as a subunit of the eIF3
      translation initiation factor and also as a transforming protein when its C
      terminal part is deleted. It includes a protein domain, which also exists in
      various subunits of eIF3, of the 26S proteasome and of the COP9 signalosome
      (CSN). By performing a two-hybrid screen with Int-6 as bait, we have isolated
      subunits belonging to all three complexes, namely eIF3-p110, Rpt4, CSN3 and CSN6.
      The results of transient expression experiments in COS7 cells confirmed the
      interaction of Int-6 with Rpt4, CSN3 and CSN6, but also showed that Int-6 is able
      to bind another subunit of the CSN: CSN7a. Immunoprecipitation experiments
      performed with the endogenous proteins showed that Int-6 binds the entire CSN,
      but in low amount, and also that Int-6 is associated with the 26S proteasome.
      Taken together these results show that the Int-6 protein can bind the three
      complexes with various efficiencies, possibly exerting a regulatory activity in
      both protein translation and degradation.

PMID- 12220627
TI  - Inositol hexakisphosphate (InsP6) can weaken the Ca(2+)-dependent membrane
      binding of C2AB domain of synaptotagmin I.
AB  - The synaptic vesicle protein synaptotagmin I has been proposed to serve as a
      Ca(2+) sensor for rapid exocytosis. In the present work, two fragments of the
      large cytoplasmic domain of synaptotagmin I, C2A and C2AB, were compared by
      combining surface plasmon resonance with circular dichroism and fluorescence
      techniques. C2AB and C2A had almost identical membrane binding constants,
      indicating that C2A is the predominate domain to bind to negatively charged
      phospholipids. After reacting with inositol hexakisphosphate (InsP6) a
      conformational change of C2AB was detected in the presence of liposome. The InsP6
      binding notably weakened the Ca(2+)-dependent C2AB-membrane interaction, which
      suggests that InsP6 may act as a modulator of neurotransmitter release by
      altering the state of synaptotagmin-phospholipid interaction.

PMID- 12220628
TI  - Identification of a dominant self-ligand bound to three HLA B44 alleles and the
      preliminary crystallographic analysis of recombinant forms of each complex.
AB  - A naturally processed and presented ligand that is shared by human leukocyte
      antigen (HLA) B*4402, B*4403 and B*4405 molecules has been identified in peptides
      isolated from immunoaffinity purified HLA B44 complexes. This peptide derived
      from HLA DPalpha residues 46-54, an endogenous product of HLA DP expressed in the
      cell line Hmy2.C1R, is a prominent peptide in the mass spectra of species
      isolated as bound peptides from each allele when the three HLA B44 subtypes were
      introduced as transfected gene products. Recombinant truncated forms of HLA
      B*4405(1-276), HLA B*4403(1-276), HLA B*4402(1-276) and beta(2)-microglobulin
      have been prepared as inclusion bodies in Escherichia coli and refolded in the
      presence of the DPalpha(46-54) peptide and purified by a combination of size
      exclusion and anion exchange chromatography. This material was determined to be
      correctly folded based on detection of a conformational epitope recognized by the
      W6/32 monoclonal antibody. Large, plate-like crystals of the three complexes were
      produced using polyethylene glycol as the precipitant. All the crystals belong to
      the space group P2(1)2(1)2(1) with unit cell dimensions of approximately a=51,
      b=82, c=110 A. The crystals of three B44/DPalpha complexes diffracted to a
      resolution of 1.9 A or better. For the first time, using this natural, high
      abundance ligand of the HLA B44 molecules we have successfully expressed and
      refolded the three HLA B44 molecules and produced crystals amenable to structural
      studies.

PMID- 12220629
TI  - X-ray structure of Galdieria Rubisco complexed with one sulfate ion per active
      site.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the reactions
      of carboxylation and oxygenation of ribulose-1,5-bisphosphate. These reactions
      require that the active site should be closed by a flexible loop (loop 6) of the
      large subunit. Rubisco from a red alga, Galdieria partita, has the highest
      specificity for carboxylation reaction among the Rubiscos hitherto reported. The
      crystal structure of unactivated Galdieria Rubisco has been determined at 2.6 A
      resolution. The electron density map reveals that a sulfate binds only to the P1
      anion-binding site of the active site and the loop 6 is closed. Galdieria Rubisco
      has a unique hydrogen bond between the main chain oxygen of Val332 on the loop 6
      and the epsilon-amino group of Gln386 of the same large subunit. This interaction
      is likely to be crucial to understanding for stabilizing the loop 6 in the closed
      state and to making a higher affinity for anionic ligands.

PMID- 12220630
TI  - OSBPa, a predicted oxysterol binding protein of Dictyostelium, is required for
      regulated entry into culmination.
AB  - The oxysterol binding proteins (OSBPs) are believed to control cholesterol
      homeostasis but their precise mechanism of action is not well understood. The
      Dictyostelium osbA gene encodes a predicted OSBP, OSBPa, which lacks the PH
      domain that in most other OSBPs directs targetting to the Golgi. OSBPa instead
      localises selectively to the cell periphery and also, in some cells, to the
      perinuclear region. OSBPa null strains form normal fruiting bodies but are
      defective in the regulation of the transition from slug migration to culmination.
      Thus a plasma membrane-enriched OSBP family member is essential for correct
      regulation of the slug-fruiting body switch.

PMID- 12220631
TI  - Different protein kinase families are activated by osmotic stresses in
      Arabidopsis thaliana cell suspensions. Involvement of the MAP kinases AtMPK3 and
      AtMPK6.
AB  - Five Ca(2+)-independent protein kinases were rapidly activated by hypoosmotic
      stress, moderate or high hyperosmolarity induced by several osmolytes, sucrose,
      mannitol or NaCl. Three of these kinases, transiently activated by
      hypoosmolarity, recognised by anti-phosphorylated mitogen-activated protein (MAP)
      kinase antibodies, sensitive to a MAP kinase inhibitor and inactivated by the
      action of a tyrosine phosphatase, corresponded to MAP kinases. Using specific
      antibodies, two of the MAP kinases were identified as AtMPK6 and AtMPK3. The two
      other protein kinases, durably activated by high hyperosmolarity, did not belong
      to the MAP kinase family. Activation of AtMPK6 and AtMPK3 by hypoosmolarity
      depended on upstream protein kinases sensitive to staurosporine and on calcium
      influx. In contrast, these two transduction steps were not involved in the
      activation of the two protein kinases activated by high hyperosmolarity.

PMID- 12220632
TI  - The cytoplasmic tail peptide sequence of membrane type-1 matrix metalloproteinase
      (MT1-MMP) directly binds to gC1qR, a compartment-specific chaperone-like
      regulatory protein.
AB  - Membrane type-1 matrix metalloproteinase (MT1-MMP), a key enzyme in cell
      locomotion, is known to be primarily recruited to the leading edge of migrating
      cells. This raises a possibility that the C-terminal cytoplasmic tail of MT1-MMP
      interacts with intracellular regulatory proteins, which modulate translocations
      of the protease across the cell. Here, we demonstrated that MT1-MMP via its
      cytoplasmic tail directly associates with a chaperone-like compartment-specific
      regulator gC1qR. Although a direct functional link between these two proteins
      remains uncertain, our observations suggest that the transient associations of
      gC1qR with the cytoplasmic tail of MT1-MMP are likely to be involved in the
      mechanisms regulating presentation of the protease at the tumor cell surface.

PMID- 12220633
TI  - Proteasomal activity modulates TGF-ss signaling in a gene-specific manner.
AB  - Transforming growth factor-beta (TGF-beta) signaling relies on Smad-signaling
      pathway controlled in part by the proteasome. Here we demonstrate that inhibition
      of the proteasome function in mink epithelial cells accumulates both positive and
      negative modulators of TGF-beta signaling, phospho-Smad2 and SnoN. Inhibition of
      the proteasome led to abrogation of TGF-beta target gene regulation in a gene
      specific manner. While regulation of p15Ink4b and myc by TGF-beta are lost, PAI-1
      induction, previously shown to occur in a Smad3-dependent manner, was not
      affected by treatment of the cells with the proteasomal inhibitor MG132. The
      results suggest that proteasomal activity is required for TGF-beta signaling in a
      gene-specific manner.

PMID- 12220634
TI  - Estradiol receptor potentiates, in vitro, the activity of 5-methylcytosine DNA
      glycosylase.
AB  - At a concentration of 5 x 10(-9) M of hemi-methylated DNA (one order of magnitude
      below the K(m)), MCF-7 (a human breast carcinoma cell line) nuclear extracts
      potentiate the activity of 5-methylcytosine DNA glycosylase (5-MCDG, alias G/T
      mismatch DNA glycosylase). Depending on the ratio between MCF-7 nuclear extracts
      and 5-MCDG, there is an up to 10-fold increase in 5-MCDG activity. The
      potentiation of 5-MCDG by MCF-7 nuclear extracts requires an estradiol response
      element adjacent to the hemi-methylated site. Depletion of the estradiol receptor
      from MCF-7 nuclear extracts with specific antibodies abolishes the potentiation
      of 5-MCDG activity. The estradiol receptor present in MCF-7 nuclear extracts can
      be precipitated with antibodies directed against 5-MCDG. Reciprocally, antibodies
      directed against the estradiol receptor precipitate 5-MCDG. The results indicate
      the formation of a complex between the estradiol receptor and 5-MCDG.

PMID- 12220635
TI  - Maltooligosaccharide disproportionation reaction: an intrinsic property of
      amylosucrase from Neisseria polysaccharea.
AB  - Amylosucrase from Neisseria polysaccharea (AS) is a remarkable transglycosidase
      of family 13 of the glycoside hydrolases that catalyses the synthesis of an
      amylose-like polymer from sucrose and is always described as a sucrose-specific
      enzyme. Here, we demonstrate for the first time the ability of pure AS to
      catalyse the disproportionation of maltooligosaccharides by cleaving the alpha
      1,4 linkage at the non-reducing end of a maltooligosaccharide donor and
      transferring the glucosyl unit to the non-reducing end of another
      maltooligosaccharide acceptor. Surprisingly, maltose, maltotriose and
      maltotetraose are very poor glucosyl donors whereas longer maltooligosaccharides
      are even more efficient glucosyl donors than sucrose. At least five glucose units
      are required for efficient transglucosylation, suggesting the existence of strong
      binding subsites, far from the sucrose binding site, at position +4 and above.

PMID- 12220636
TI  - The COOH-terminus of parathyroid hormone-related protein (PTHrP) interacts with
      beta-arrestin 1B.
AB  - Parathyroid hormone-related protein (PTHrP) has a diverse range of proposed
      biological activities participating in both extracellular and intracellular
      signaling. In order to identify candidate protein effectors, yeast two-hybrid
      screens were conducted using mature human PTHrP (residues 1-141) and the COOH
      terminus (residues 107-141). Both PTHrP baits interacted with a beta-arrestin 1B
      fragment, an important component of G-protein-coupled receptor desensitization
      and MAPK signaling. Co-immunoprecipitation, in vitro binding assays and
      colocalization experiments confirmed this interaction in human cells and this
      required residues 122-141 of PTHrP. These findings suggest that beta-arrestin 1
      acts as an effector for a novel function of PTHrP in cytoplasm.

PMID- 12220637
TI  - Evidence for non-isostructural replacement of Zn(2+) with Cd(2+) in the beta
      domain of brain-specific metallothionein-3.
AB  - Metallothionein-3 (MT-3) is a brain-specific MT, which is downregulated in
      Alzheimer's disease. The N-terminal region of CdMT-3 is highly dynamic and has
      escaped structural characterization by nuclear magnetic resonance. We have used
      electrospray ionization mass spectrometry to probe conformational states of
      cadmium- and zinc-substituted metalloforms of MT-3 and can demonstrate that the N
      terminal beta-domain of MT-3 filled with Cd(2+) has a more open conformation than
      that filled with Zn(2+). The results suggest that the larger Cd(2+) ions cannot
      isostructurally replace zinc in the beta-domain of MT-3 whereas in the case of MT
      1 and MT-2 the replacement is isostructural. Specific metal binding properties of
      the beta-domain of MT-3 may be essential for fulfilling the specific role of MT-3
      in the brain.

PMID- 12220638
TI  - Activation volumes for intramolecular electron transfer in Escherichia coli
      cytochrome bo(3).
AB  - In this report we describe the activation volumes associated with the heme-heme
      electron transfer (ET) and CO rebinding to the binuclear center subsequent to
      photolysis of the CO-mixed-valence derivative of Escherichia coli cytochrome
      bo(3) (Cbo). The activation volumes associated with the heme-heme ET (k=1.2 x
      10(5) s(-1)), and CO rebinding (k=57 s(-1)) are found to be +27.4 ml/mol and -2.6
      ml/mol, respectively. The activation volume associated with the rebinding of CO
      is consistent with previous Cu X-ray absorption studies of Cbo where a structural
      change was observed at the Cu(B) site (loss of a histidine ligand) due to a
      change in the redox state of the binuclear center. In addition, the volume of
      activation for the heme-heme ET was found to be quite distinct from the
      activation volumes obtained for heme-heme ET in bovine heart Cytochrome c
      oxidase. Differences in mechanisms/pathways for heme b/heme o(3) and heme a/heme
      a(3) ET are suggested based on the associated activation volumes and previously
      obtained Marcus parameters.

PMID- 12220639
TI  - The temperature dependence of the hydrogen exchange in the SH3 domain of alpha
      spectrin.
AB  - The amide hydrogen-deuterium exchange (HX) in the Src homology region 3 (SH3)
      domain of alpha-spectrin has been measured by nuclear magnetic resonance as a
      function of temperature between 8 and 46 degrees C. The analysis of the
      temperature dependence of HX from a statistical thermodynamic point of view has
      allowed us to estimate the enthalpies and entropies of the conformational
      processes leading to HX. The results indicate that under native conditions the
      domain undergoes a wide variety of conformational fluctuations, ranging from
      local motions, mainly located in loops, turns and chain ends and involving only
      low enthalpy and entropy, to extensive structural disruptions affecting its core
      and involving enthalpies and entropies that come fairly close to those observed
      during global unfolding.

PMID- 12220640
TI  - Activity, tissue distribution and site-directed mutagenesis of a human peptide
      methionine sulfoxide reductase of type B: hCBS1.
AB  - Human CBS1 is a methionine sulfoxide reductase of type B (MSRB) as it
      specifically reduced Met-R-SO in peptides with dithiothreitol or the thioredoxin
      system as reductants. Mutation C169S in the active site completely abolished
      enzymatic activity, while mutation W110A only reduced activity and C105S had no
      effect. Like human MSRA, hCBS1 showed in vivo reducing activity coexpressed with
      the Drosophila ShC/B potassium channel in oocytes, by accelerating the overall
      inactivation time course. hCBS1-encoding mRNA is most abundant in muscle tissues,
      especially in the heart and thereby shows an expression pattern different to the
      human MSRA.

PMID- 12220641
TI  - Protection against experimental malaria associated with AMA-1 peptide analogue
      structures.
AB  - One Plasmodium falciparum malaria antigen is an integral membrane protein called
      apical membrane antigen-1. High activity binding peptides to human red blood
      cells have been identified in this protein. 4337 is a conserved, non-immunogenic
      peptide with high activity red blood cell binding and its critical residues have
      already been identified. Peptide analogues (with amino acids having the same mass
      but different charge) were generated to change their immunogenic and protective
      characteristics. Three analogues having positive or negative immunological
      results were studied by nuclear magnetic resonance. The studied peptides all had
      an alpha-helix fragment, but in different peptide regions and extensions, except
      for randomly structured 4337. We show that altering a few amino acids induced
      immunogenicity and protectivity against experimental malaria and changed their
      three-dimensional structure, suggesting a better fit with immune system molecules
      and that modified peptides having better immunological properties can be included
      in the design of new malaria multi-component subunit-based vaccine.

PMID- 12220642
TI  - Phosphorylation of the regulatory subunit of smooth muscle protein phosphatase 1M
      at Thr850 induces its dissociation from myosin.
AB  - Rho kinase is known to control smooth muscle contractility by phosphorylating the
      110 kDa myosin-targetting subunit (MYPT1) of the myosin-associated form of
      protein phosphatase 1 (PP1M). Phosphorylation of MYPT1 at Thr695 has previously
      been reported to inhibit the catalytic activity of PP1. Here, we show that the
      phosphorylation of Thr850 by Rho kinase dissociates PP1M from myosin, providing a
      second mechanism by which myosin phosphatase activity is inhibited.

PMID- 12220643
TI  - End-joining of reconstituted histone H2AX-containing chromatin in vitro by
      soluble nuclear proteins from human cells.
AB  - Non-homologous end-joining is an important pathway for the repair of DNA double
      strand breaks. This type of DNA break is followed by the rapid phosphorylation of
      Ser-139 in the histone variant H2AX to form gamma-H2AX. Here we report efficient
      in vitro end-joining of reconstituted chromatin containing nucleosomes made with
      either H2A or H2AX. This reaction is catalyzed by nuclear extracts from human
      cells and this end-joining is not suppressed by the PI-3 kinase inhibitor
      wortmannin. During the end-joining reaction H2AX is phosphorylated at Ser-139 as
      detected by immunoblot with specific antibodies and this phosphorylation is
      inhibited by wortmannin. Therefore, in vitro the DNA end-joining reaction appears
      to be independent of H2AX phosphorylation.

PMID- 12220644
TI  - Human gastrin-releasing peptide receptor mediates sustained CREB phosphorylation
      and transactivation in HuTu 80 duodenal cancer cells.
AB  - The G protein-coupled human gastrin-releasing peptide receptor (hGRP-R) is
      frequently found aberrantly expressed in human cancers of the colon, stomach, and
      lung, and its ligand-specific activation has been implicated in cell
      proliferation and differentiation. Here, we demonstrated hGRP-R activation
      stimulated sustained cyclic AMP response element binding protein (CREB)
      phosphorylation and transactivation in duodenal cancer cells through a protein
      kinase C and partially p38 mitogen-activated protein kinase-dependent pathway. In
      contrast, intracellular calcium, ERK1/2, protein kinase A, and PI3 kinase were
      not involved. This novel signaling mechanism might be of importance for
      regulation of CREB-dependent gene expression in human cancer expressing
      functional hGRP-R.

PMID- 12220645
TI  - A novel repeat in the melanoma-associated chondroitin sulfate proteoglycan
      defines a new protein family.
AB  - The human melanoma-associated chondroitin sulfate proteoglycan (MCSP) and its rat
      ortholog NG2 are thought to play important roles in angiogenesis-dependent
      processes like wound healing and tumor growth. Based on electron microscopy
      studies, the highly glycosylated ectodomain of NG2 has been subdivided into the
      globular N-terminus, a flexible rod-like central region and a C-terminal portion
      in globular conformation. We identified a novel repeat named CSPG in the central
      ectodomain of NG2, MCSP and other proteins from fly, worm, human, sea urchin and
      a cyanobacterium which shows similarity to cadherin repeats. As earlier electron
      microscopy studies indicate, the folding of the tandem repeats compresses the
      length of the proposed repeat region by a factor of approximately 10 compared to
      the fully extended peptide chain. We identified two conserved negatively charged
      residues which might govern the binding properties of CSPG repeats. The phyletic
      distribution of CSPG repeats suggests that horizontal gene transfer contributed
      to their evolutionary history.

PMID- 12220646
TI  - Involvement of Elk-1 in L6E9 skeletal muscle differentiation.
AB  - In L6E9 skeletal muscle cells ternary complex factor (TCF) Elk-1 expression
      increased with the onset of skeletal muscle differentiation, whereas its
      activation decreased as a function of differentiation. Its expression was
      predominantly restricted to cytoplasm and activated ones were predominantly
      restricted to the nucleus of the differentiated cells. Inhibition of ERK-1/-2
      activities by PD098059 resulted into significant reduction in Elk-1 expression
      and phosphorylation during differentiation. In contrast, inhibition of p38
      mitogen-activated protein kinase (MAPK) enhanced Elk-1 expression and activation,
      thereby mediating inhibition of skeletal muscle differentiation. Overexpression
      of inactive mutant Elk-1 enhanced differentiation. Data suggest that ERK-1/-2 and
      p38 MAPK activities modulate Elk-1 expression and activation to regulate skeletal
      muscle differentiation.

PMID- 12220647
TI  - Differential effect of pH on sodium binding by the various GABA transporters
      expressed in Xenopus oocytes.
AB  - Mouse GABA transporters belong to the family of Na(+)- and Cl(-)-dependent
      neurotransmitter transporters. The four GABA transporters exhibit unique
      presteady-state currents when expressed in Xenopus oocytes. The properties of the
      presteady-state currents correspond to their different affinities to Na(+). In
      the presence of 20 microM GABA and at pH 7.5, the half-maximal uptake activity
      was 47, 120, 25 and 35 mM Na(+) for GAT1, GAT2, GAT3 and GAT4, respectively. The
      appearance of presteady-state currents at positive or negative imposed potentials
      was in correlation with the affinity to Na(+). Changing the external pH
      differentially affected the GABA uptake and the presteady-state activities of the
      various GABA transporters. It is suggested that protons compete with Na(+) on its
      binding site; however, the proton binding is not productive and is unable to
      drive GABA uptake.

PMID- 12220648
TI  - N-acetylcysteine prevents MAA induced male germ cell apoptosis: role of
      glutathione and cytochrome c.
AB  - Exposure to methoxyacetic acid (MAA), a major byproduct of the paint industry,
      causes testicular atrophy in multiple species. This study demonstrates DNA
      breakdown in rat germ cells after exposure to MAA in vivo within 12 h, leading to
      40% germ cell death by 24 h. Within 4 h of treatment, cytochrome c is released
      from the mitochondria into the cytosol without the involvement of mitochondrial
      potential loss, reactive oxygen species generation or lipid peroxidation events.
      Peak activation of caspase-9 and caspase-3 is detectable post treatment at 4 and
      8 h respectively. There is a decrease in germ cell glutathione levels within 2 h
      of MAA treatment. Replenishment of glutathione by pretreatment of the animals
      with the antioxidant N-acetylcysteine prior to MAA treatment could prevent the
      release of cytochrome c, DNA fragmentation and cell death.

PMID- 12220649
TI  - Novel strategy for anti-HIV-1 action: selective cytotoxic effect of N
      myristoyltransferase inhibitor on HIV-1-infected cells.
AB  - N-myristoyltransferase (NMT) is essential for the survival of eukaryotes and the
      production of infectious human immunodeficiency virus type-1(HIV-1) by the host
      cell. In this study, we found decreases in the mRNA levels of human NMT isoforms
      and the NMT activities in the course of HIV-1 infection in the human T-cell line,
      CEM. Investigating the cytotoxic effect of the novel synthetic NMT inhibitors on
      the chronic HIV-1 infected T-cell line, CEM/LAV-1, and the uninfected CEM,
      revealed that the cytotoxic effect was significantly selective for CEM/LAV-1.
      This was thought to be due to the difference between the NMT levels of the cell
      lines. In this paper, we propose that NMT may be a candidate target for anti-HIV
      1-infected-cell agents.

PMID- 12220650
TI  - Control of complex formation of DNA polymerase alpha-primase and cell-free DNA
      replication by the C-terminal amino acids of the largest subunit p180.
AB  - DNA polymerase alpha-primase is a heterotetrameric complex essential for simian
      vacuolating virus 40 (SV40) DNA replication. We show that the C-terminal 67 amino
      acid residues of the human p180 subunit are essential for SV40 DNA replication as
      they are required for binding of the p68 subunit and play a role in the
      interaction with the primase subunits, p48 and p58. Furthermore, we demonstrate
      that exchanging these residues to those of mouse origin can only partially rescue
      the SV40 DNA replication activity of DNA polymerase alpha-primase.

PMID- 12220651
TI  - Stepwise rotation of the gamma-subunit of EF(0)F(1)-ATP synthase observed by
      intramolecular single-molecule fluorescence resonance energy transfer.
AB  - The EF(0)F(1)-ATP synthase mutants bQ64C and gamma T106C were labelled
      selectively with the fluorophores tetramethylrhodamine (TMR) at the b-subunit and
      with a cyanine (Cy5) at the gamma-subunit. After reconstitution into liposomes,
      these double-labelled enzymes catalyzed ATP synthesis at a rate of 33 s(-1).
      Fluorescence of TMR and Cy5 was measured with a confocal set-up for single
      molecule detection. Photon bursts were detected, when liposomes containing one
      enzyme traversed the confocal volume. Three states with different fluorescence
      resonance energy transfer (FRET) efficiencies were observed. In the presence of
      ATP, repeating sequences of those three FRET-states were identified, indicating
      stepwise rotation of the gamma-subunit of EF(0)F(1).

PMID- 12220652
TI  - Intracellular localization of Herpes simplex virus type 1 thymidine kinase fused
      to different fluorescent proteins depends on choice of fluorescent tag.
AB  - Gene therapy employing the suicide gene/prodrug activating system Herpes simplex
      virus type 1 thymidine kinase (HSV-TK)/ganciclovir (GCV) is effective in killing
      malignant tumor cells. Labeling of the HSV-TK enzyme with fluorescent proteins
      makes possible the non-invasive imaging of transduction efficiency, enzyme
      localization and activity in cell culture and in animal models of human cancers.
      Here we report the expression of HSV-TK tagged with different fluorescent
      proteins (EGFP, DSRed1, DsRed2, dsdrFP616) and show that intracellular
      localization of the fusion products depends on the nature of the fluorescent tag
      despite the presence of several nuclear targeting signals within the enzyme
      itself. Coexpression of red fluorescent HSV-TK fusion proteins with TK-EGFP or
      untagged HSV-TK allowed these proteins to enter the nucleus by inhibiting
      formation of red fluorescent protein oligomers. As enzyme localization may
      influence HSV-TK activity, this observation is of potential importance to gene
      therapy studies.

PMID- 12220654
TI  - Desolvation shell of hydrogen bonds in folded proteins, protein complexes and
      folding pathways.
AB  - A few backbone hydrogen bonds (HBS) in native protein folds are poorly protected
      from water attack: their desolvation shell contains an inordinately low number of
      hydrophobic residues. Thus, an approach by solvent-structuring moieties of a
      binding partner should contribute significantly to enhance their stability. This
      effect represents an important factor in the site specificity inherent to protein
      binding, as inferred from a strong correlation between poorly desolvated HBs and
      binding sites. The desolvation shells were also examined in a dynamic context:
      except for a few singular under-protected bonds, the size of desolvation shells
      is preserved along the folding trajectory.

PMID- 12220653
TI  - SecY-SecY and SecY-SecG contacts revealed by site-specific crosslinking.
AB  - Protein translocation across the cytoplasmic membrane of Escherichia coli is
      mediated by the integral membrane complex SecYEG and the peripherally bound
      ATPase SecA. To probe the environment of the cytoplasmic domains of SecY within
      the SecYEG complex, we introduced single cysteine residues in each of the six
      cytoplasmic domains. Neighbouring SecY molecules with a single cysteine residue
      in cytoplasmic domains C1, C2 or C6 formed a disulfide bond upon oxidation. The
      presence of the disulfide bond between two C2 domains reversibly inhibited
      protein translocation. Chemical crosslinking showed that the C2 and C3 domains
      are in close proximity of SecG and chemical modification of the cysteine residue
      in the C5 domain with N-ethyl-maleimide or fluorescein-5-maleimide inactivates
      the SecYEG complex. Taken together, our data give novel insights in the
      interactions between subunits of the SecYEG complex and emphasise the importance
      of cytoplasmic domain C5 for SecY functioning.

PMID- 12220655
TI  - Tuning of the redox potential of the primary electron donor in reaction centres
      of purple bacteria: effects of amino acid polarity and position.
AB  - Mutation of residues His L168 and Phe M197 in the reaction centre from
      Rhodobacter sphaeroides has an unusually strong effect on the mid-point redox
      potential (E(m)) of the pair of bacteriochlorophylls that form the primary donor
      of electrons, tuning E(m) over a range of nearly 250 mV. This effect is
      correlated to the accompanying change in the permanent dipole of the L168 or M197
      residue, suggesting it is mediated by changes in charge-dipole interactions.
      Comparisons with mutations made at a variety of other positions show that this
      correlation is particular to this residue pair, perhaps reflecting their
      proximity to the ring I regions of the dimer bacteriochlorophylls that form the
      overlap region between these molecules.

PMID- 12220656
TI  - Characterization of the spermidine synthase-related gene family in Arabidopsis
      thaliana.
AB  - The Arabidopsis genome contains four genes that encode proteins similar to both
      spermidine synthase and spermine synthase of other organisms. Our previous study
      revealed that one of these genes, designated ACAULIS5 (ACL5), encodes spermine
      synthase and that its null mutation results in a severe defect in the elongation
      of stem internodes. Here we report the characterization of the other three genes,
      designated SPDS1, SPDS2 and SPDS3. Our results showed that SPDS1 and SPDS2
      possess spermidine synthase activity in yeast spermidine synthase-deficient
      mutants, but the enzyme activity of SPDS3 remained to be determined. RNA gel blot
      analysis revealed that all of these genes are expressed in all plant organs but
      show different responses to exogenous plant hormones, suggesting that they are
      involved in different aspects of growth by modulating the contents of polyamines
      in plant cells.

PMID- 12220657
TI  - A single nucleotide polymorphism in the alternative oxidase gene among rice
      varieties differing in low temperature tolerance.
AB  - Alternative oxidase (AOX) is encoded in a multigene family, and multiple isoforms
      have been observed in various plant species. We found for the first time an
      allelic variation in the same AOX locus. On SDS-gel blots of callus protein of
      rice (Oryza sativa L.), varieties without the QTL for low temperature tolerance
      showed a 32-kDa AOX band, whereas those with the QTL showed a 34-kDa band. The
      variation was attributed to the substitution of Lys(71) for Asn(71) caused by a
      single nucleotide polymorphism between alleles of OsAOX1a, and was tightly linked
      to the presence of the QTL.

PMID- 12220658
TI  - YIL113w encodes a functional dual-specificity protein phosphatase which
      specifically interacts with and inactivates the Slt2/Mpk1p MAP kinase in S.
      cerevisiae.
AB  - We show here that the YIL113w gene of Saccharomyces cerevisiae encodes a
      functional protein phosphatase. Yil113p shows no activity in vitro towards either
      phosphorylated casein or myelin basic protein. However, Yil113p dephosphorylates
      activated extracellular signal-regulated kinase 2 MAP kinase indicating that it
      is a dual-specificity MAP kinase phosphatase. In support of this we find that
      Yil113p specifically interacts with the stress-activated Slt2/Mpk1p MAP kinase of
      S. cerevisiae. Furthermore, expression of Yil113p causes the dephosphorylation of
      Slt2/Mpk1p in vivo, while expression of an inactive mutant of Yil113p causes the
      accumulation of phosphorylated Slt2/Mpk1p. We conclude that the physiological
      target of YIL113p is Slt2/Mpk1p.

PMID- 12220659
TI  - Cupiennin 1d*: the cytolytic activity depends on the hydrophobic N-terminus and
      is modulated by the polar C-terminus.
AB  - To investigate structural features modulating the biological activity of
      cupiennin 1 peptides from the spider Cupiennius salei, three truncated cupiennin
      1d analogs were synthesized. The fact that their growth inhibiting effect on Gram
      negative and Gram-positive bacteria, their lytic activity with human red blood
      cells and their insecticidal effect on Drosophila melanogaster correlates with
      structural properties shows that the hydrophobic N-terminal chain segment
      includes the major determinants of structure and activity. The polar C-terminus
      seems to modulate peptide accumulation at negatively charged cell surfaces via
      electrostatic interactions and has no important effect on the peptides'
      amphipathic secondary structure.

PMID- 12220660
TI  - Comparative characterization of Aedes 3-hydroxykynurenine transaminase/alanine
      glyoxylate transaminase and Drosophila serine pyruvate aminotransferase.
AB  - This study describes the comparative analysis of two insect recombinant
      aminotransferases, Aedes aegypti 3-hydroxykynurenine (3-HK) transaminase/alanine
      glyoxylate aminotransferase (Ae-HKT/AGT) and Drosophila melanogaster serine
      pyruvate aminotransferase (Dm-Spat), which share 52% identity in their amino acid
      sequences. Both enzymes showed AGT activity. In addition, Ae-HKT/AGT is also able
      to catalyze the transamination of 3-HK or kynurenine with glyoxylate, pyruvate or
      oxaloacetate as the amino acceptor. Kinetic analysis and other data suggest that
      Ae-HKT/AGT plays a critical role in mosquito tryptophan catabolism by detoxifying
      3-HK and that Dm-Spat is primarily involved in glyoxylate detoxification.

PMID- 12220661
TI  - Human immune cells express ppMCH mRNA and functional MCHR1 receptor.
AB  - Melanin-concentrating hormone (MCH) is highly expressed in the brain and
      modulates feeding behavior. It is also expressed in some peripheral tissues where
      its role remains unknown. We have investigated MCH function in human and mouse
      immune cells. RT-PCR analysis revealed a low expression of prepro-MCH and MCH
      receptor 1 (MCHR1) but not of MCHR2 transcript in tissular and peripheral blood
      immune cells. FACS and in vitro assay studies demonstrated that MCHR1 receptor
      expression on most cell types can trigger, in the presence of MCH, cAMP synthesis
      and calcium mobilization in peripheral blood mononuclear cells (PBMCs). Moreover,
      MCH treatment decreases the CD3-stimulated PBMC proliferation in vitro.
      Accordingly, our data indicate for the first time that MCH and MCHR1 may exert
      immunomodulatory functions.

PMID- 12220662
TI  - Effect of Bacillus anthracis lethal toxin on human peripheral blood mononuclear
      cells.
AB  - Lethal toxin (LeTx) plays a central role in anthrax pathogenesis, however a
      cytotoxicity of LeTx has been difficult to demonstrate in vitro. No cytolytic
      effect has been reported for human cells, in contrast to murine cell lines,
      indicating that cell lysis can not be considered as a marker of LeTx activity. We
      have recently shown that murine macrophage-like RAW 264.7 cells treated with LeTx
      or infected with anthrax spores underwent changes typical of apoptotic death.
      Here we demonstrate that cells from human peripheral blood display a proapoptotic
      behavior similar to murine cells. TUNEL assay detected a nucleosomal degradation
      typical of apoptosis in peripheral blood mononuclear cells (PBMC) treated with
      LeTx. Membrane staining with apoptotic dyes was detected in macrophages derived
      from monocytes in presence of LeTx. The toxin inhibited production of
      proinflammatory cytokines in PBMC stimulated with a preparation of Bacillus
      anthracis cell wall. Infection of PBMC with anthrax spores led to the appearance
      of a large population of cells stained positively for apoptosis, with a reduced
      capacity to eliminate spores and vegetative bacteria. The aminopeptidase
      inhibitor, bestatin, capable of protecting cells from LeTx, restored a
      bactericidal activity of infected cells. These findings may be explained by LeTx
      expression within phagocytes and support an important role of LeTx as an early
      intracellular virulence factor contributing to bacterial dissemination and
      disease progression.

PMID- 12220663
TI  - The expression of the non-receptor tyrosine kinases Arg and c-abl is differently
      modulated in B lymphoid cells at different stages of differentiation.
AB  - The products of the human ARG gene and the human ABL gene characterize the
      Abelson family of non-receptor tyrosine protein kinases. Both genes are
      ubiquitously expressed. The interactions of these two similar protein kinases are
      still not well known, although it has been suggested that they could cooperate,
      with redundant actions, to provide intracellular signals in the cells.
      Lymphopenia occurs in mice with homozygous disruption of c-abl, indicating that
      in certain tissues Arg is unable to substitute c-abl functions. In B and T
      lymphoid cell lines at different stages of differentiation, we studied, by a
      reverse transcriptase-competitive polymerase chain reaction and Western blotting,
      Arg and c-abl in order to evaluate whether the expression pattern of the two
      genes could give insight as to why they do not exhibit overlapping roles in
      lymphocytes and whether the product levels of the two genes are related to
      lymphoid differentiation. The data showed that their expression is differently
      modified in lymphoid B cell lines. The highest Arg transcript and protein levels
      are in the mature B cells.

PMID- 12220665
TI  - Retinoic acid reduces the cytotoxicity of cyclopentenyl cytosine in neuroblastoma
      cells.
AB  - In this paper, it is demonstrated that all-trans, 9-cis and 13-cis retinoic acid
      (RA) decreased the sensitivity of SK-N-BE(2)c neuroblastoma cells towards the
      chemotherapeutic agent cyclopentenyl cytosine (CPEC), a potent inhibitor of
      cytosine-5'-triphosphate synthetase. Retinoic acid attenuated CPEC-induced
      apoptosis as reflected by a decreased caspase-3 induction. Retinoic acid
      decreased the accumulation of CPEC, whereas the salvage of cytidine was strongly
      increased. Metabolic labeling studies using [(3)H]uridine showed a strongly
      decreased biosynthesis of CTP via CTP synthetase. Retinoic acid likely confers
      resistance of neuroblastoma cells to CPEC in part by slowing down proliferation,
      and in part by shifting the synthesis of CTP towards the salvage of cytidine,
      thereby bypassing CTP synthetase.

PMID- 12220666
TI  - Chaperone-like activity and surface hydrophobicity of 70S ribosome.
AB  - Ribosomes have been shown to mediate refolding of proteins in vitro. In order to
      understand the mechanism of action, we have explored the 70S ribosome surface for
      hydrophobicity, one of the important aspects in chaperone-target protein
      interaction. We find that the 70S ribosome displays significant hydrophobicity on
      its surface when probed with the hydrophobic fluorophore 8-anilino-1-naphthalene
      sulfonate. To understand the functional significance of this hydrophobicity we
      investigated the ability of the ribosome to prevent aggregation of insulin B
      chain and alpha-lactalbumin induced by reducing the interchain and intrachain
      disulfide bond respectively with dithiothreitol (DTT) and photo aggregation of
      gamma-crystallin at 37 degrees C. The 70S ribosome offers complete protection
      towards light-induced aggregation of gamma-crystallin (at 1:2 (w/w) ratio of
      crystallin:ribosome) and DTT-induced aggregation of alpha-lactalbumin (at 1:3)
      and there is appreciable protection (at 1:3) against the aggregation of insulin B
      chain. We also investigated the role of 70S ribosome in refolding of bovine
      carbonic anhydrase. Ribosomes improved the folding yield in a concentration
      dependent manner. These results clearly demonstrate a general chaperone-like
      activity of 70S ribosome and implicate its surface hydrophobicity.

PMID- 12220664
TI  - Caspase activation in etoposide-treated fibroblasts is correlated to ERK
      phosphorylation and both events are blocked by polyamine depletion.
AB  - Activation of the extracellular signal-regulated kinases (ERKs) 1 and 2 is
      correlated to cell survival, but in some cases ERKs can act in signal
      transduction pathways leading to apoptosis. Treatment of mouse fibroblasts with
      20 microM etoposide elicited a sustained phosphorylation of ERK 1/2, that
      increased until 24 h from the treatment in parallel with caspase activity. The
      inhibitor of ERK activation PD98059 abolished caspase activation, but caspase
      inhibition did not reduce ERK 1/2 phosphorylation, suggesting that ERK activation
      is placed upstream of caspases. Both ERK and caspase activation were blocked in
      cells depleted of polyamines by the ornithine decarboxylase inhibitor alpha
      difluoromethylornithine (DFMO). In etoposide-treated cells, DFMO also abolished
      phosphorylation of c-Jun NH(2)-terminal kinases triggered by the drug. Polyamine
      replenishment with exogenous putrescine restored the ability of the cells to
      undergo caspase activation and ERK 1/2 phosphorylation in response to etoposide.
      Ornithine decarboxylase activity decreased after etoposide, indicating that DFMO
      exerts its effect by depleting cellular polyamines before induction of apoptosis.
      These results reveal a role for polyamines in the transduction of the death
      signal triggered by etoposide.

PMID- 12220667
TI  - Effects of copper on the expression of metal transporters in human intestinal
      Caco-2 cells.
AB  - Copper is an essential dietary trace metal, however the mechanisms involved in
      intestinal copper uptake are unclear. Two putative copper transporters are
      expressed in Caco-2 cells, the divalent metal transporter (DMT1) and copper
      transporter (Ctr1). Our data demonstrate that copper could compete with iron for
      uptake via DMT1 and that DMT1 protein and mRNA expression were decreased
      following exposure (24 h) to high copper. Expression of Ctr1, which acts as a
      copper transporter in transfected cell lines, was unaffected by copper treatment.
      Interestingly, exposure to copper increased iron efflux from Caco-2 cells and up
      regulated IREG1 (iron-regulated mRNA) expression.

PMID- 12220668
TI  - Identification of a pH regulated Na(+)/H(+) antiporter of Methanococcus
      jannaschii.
AB  - The genome of the hyperthermophilic archaeon Methanococcus jannaschii contains
      three Na(+)/H(+) antiporter related genes Mj0057, Mj1521 and Mj1275. Comparative
      sequence alignments revealed that Mj0057 and Mj1521 belong to the NhaP family
      whereas Mj1275 is a member of the NapA family. The genes were cloned and
      expressed in the double mutant Escherichia coli strain Frag144 (DeltanhaA,
      DeltanhaB) to analyze their capability of mediating DeltapH driven Na(+) flux in
      everted vesicles. From the tested clones only Mj0057 displayed Na(+) (Li(+))/H(+)
      antiporter activity. The transport was pH dependent and occurred at pH 7.0 and
      below. At pH 6.0 the apparent K(m) values for Na(+) and Li(+) were approximately
      10 and 2.5 mM, respectively.

PMID- 12220669
TI  - Identification of a basic surface area of the FADD death effector domain critical
      for apoptotic signaling.
AB  - Death effector domains (DEDs) are protein-protein interaction domains found in
      the death inducing signaling complex (DISC). Performing a structure-based
      alignment of all DED sequences we identified a region of high diversity in alpha
      helix 3 and propose a classification of DEDs into class I DEDs typically
      containing a stretch of basic residues in the alpha-helix 3 region whereas DEDs
      of class II do not. Functional assays using mutants of Fas-associated death
      domain revealed that this basic region influences binding and recruitment of
      caspase-8 and cellular FLICE inhibitor protein to the DISC.

PMID- 12220670
TI  - Chemokine receptor inhibition by AMD3100 is strictly confined to CXCR4.
AB  - This study was undertaken to demonstrate the unique specificity of the chemokine
      receptor CXCR4 antagonist AMD3100. Calcium flux assays with selected
      chemokine/cell combinations, affording distinct chemokine receptor specificities,
      revealed no interaction of AMD3100 with any of the chemokine receptors CXCR1
      through CXCR3, or CCR1 through CCR9. In contrast, AMD3100 potently inhibited
      CXCR4-mediated calcium signaling and chemotaxis in a concentration-dependent
      manner in different cell types. Also, AMD3100 inhibited stromal cell-derived
      factor (SDF)-1-induced endocytosis of CXCR4, but did not affect phorbol ester
      induced receptor internalization. Importantly, AMD3100 by itself was unable to
      elicit intracellular calcium fluxes, to induce chemotaxis, or to trigger CXCR4
      internalization, indicating that the compound does not act as a CXCR4 agonist.
      Specific small-molecule CXCR4 antagonists such as AMD3100 may play an important
      role in the treatment of human immunodeficiency virus infections and many other
      pathological processes that are dependent on SDF-1/CXCR4 interactions (e.g.
      rheumatoid arthritis, atherosclerosis, asthma and breast cancer metastasis).

PMID- 12220671
TI  - Toxicity evolution of Vipera aspis aspis venom: identification and molecular
      modeling of a novel phospholipase A(2) heterodimer neurotoxin.
AB  - We report the simultaneous presence of two phospholipase A(2) (PLA(2))
      neurotoxins in the venom of Vipera aspis aspis, the first such observation. One
      is monomeric and identical to ammodytoxin B of Vipera ammodytes ammodytes. Its
      presence may result from gene flux after interbreeding between V. aspis aspis and
      V. ammodytes ammodytes. The second, a novel heterodimer named vaspin, is very
      similar to vipoxin of Vipera ammodytes meridionalis and to PLA(2)-I of Vipera
      aspis zinnikeri. It may result from expression of preexisting genes, the acidic
      subunit evolving from an ancestor common to ammodytin I2 from V. ammodytes
      ammodytes, which we also found in V. aspis aspis.

PMID- 12220672
TI  - Glutamate-induced calcium increase in myotubes depends on up-regulation of a
      sodium-dependent transporter.
AB  - We report a study on the regulation by 2-chloro adenosine (2CA) of a glutamate
      (Glu) transporter in myogenic C2C12 cells. Long-term 2CA exposition significantly
      increased the V(max) of the Glu transporter. Moreover, 2CA-treated cells
      responded to Glu challenge by a rapid and transient increase in their
      intracellular calcium level. The above reported effects were totally abolished by
      treating C2C12 cells with the Na(+)-dependent Glu transporter inhibitors DL-threo
      b-hydroxyaspartic acid and L-trans-pyrrolidine-2,4-dicarboxylic acid. We propose
      that the possible link between the Glu uptake increase and the Glu induction of
      calcium rise could be the depolarizing currents carried by Na(+) coupled with
      transporter activity.

PMID- 12220673
TI  - Silencing of Bruton's tyrosine kinase (Btk) using short interfering RNA duplexes
      (siRNA).
AB  - Tec family tyrosine kinases, Bruton's tyrosine kinase (Btk), Itk, Bmx, Tec, and
      Txk, are multi-domain proteins involved in hematopoietic signaling. Here, we
      demonstrate that human Btk protein can transiently be depleted using double
      stranded short RNA interference (siRNA) oligonucleotides. Imaging and Western
      blotting analysis demonstrate that Btk expression is down regulated in
      heterologous systems as well as in hematopoietic lineages, following transfection
      or microinjection of Btk siRNA duplexes. The induction of histamine release, a
      pro-inflammatory mediator, in RBL-2H3 mast cells was reduced by 20-25% upon Btk
      down regulation. Similar, results were obtained when the Btk activity was
      inhibited using the kinase blocker LFM-A13. These results demonstrate a direct
      role of Btk for the efficient secretion of histamine in allergic responses.

PMID- 12220674
TI  - A selective effect of Mpl ligand on mRNA stabilization during megakaryocyte
      differentiation.
AB  - Megakaryocytes, the platelet precursors, are induced to differentiate in response
      to Mpl ligand. Here we report that stability of the megakaryocyte-specific
      platelet factor 4 (PF4) mRNA is substantially augmented in the presence of Mpl
      ligand. This stabilization requires protein synthesis, but the 3'-untranslated
      region of PF4 mRNA is not sufficient for granting the effect. This cytokine also
      significantly or mildly stabilizes Mpl receptor or GAPDH mRNAs, respectively, in
      contrast to a previously reported lack of effect on P2Y(1) receptor mRNA. Our
      study is the first to suggest that Mpl ligand-induced lineage specification is
      also determined by message stabilization.

PMID- 12220675
TI  - Endothelin suppresses cell migration via the JNK signaling pathway in a manner
      dependent upon Src kinase, Rac1, and Cdc42.
AB  - Cell migration is a complex phenomenon that is stimulated by chemoattractive
      factors such as chemokines, a family of ligands for G protein-coupled receptors
      (GPCRs). In contrast, factors that suppress cell migration, and the mechanism of
      their action, remain largely unknown. In this study, we show that endothelin, a
      GPCR ligand, inhibits cell motility in a manner dependent upon signaling through
      the c-Jun N-terminal kinase (JNK) pathway. We further demonstrate that this
      effect is dependent upon Src kinase and small GTPases Rac1 and Cdc42. These
      findings provide new insight into GPCR-mediated regulation of cell migration.

PMID- 12220676
TI  - Inactivation of cellular caspases by peptide-derived tryptophan and tyrosine
      peroxides.
AB  - Peroxides generated on peptides and proteins within cells, as a result of radical
      attack or reaction with singlet oxygen, are longer-lived than H(2)O(2) due to
      their poor removal by protective enzymes. These peroxides readily oxidize
      cysteine residues and can inactivate thiol-dependent enzymes. We show here that
      Trp- and Tyr-derived peptide peroxides, generated by singlet oxygen, inhibit
      caspase activity in the lysates of apoptotic Jurkat cells. N-Ac-Trp-OMe peroxide
      was the most effective inhibitor, and was 30-fold more effective than H(2)O(2)
      under identical conditions. As such, protein peroxides could modulate the
      progression of apoptosis in cells in which they are generated.

PMID- 12220677
TI  - Insulin-like growth factor binding protein-3 increases intracellular calcium
      concentrations in MCF-7 breast carcinoma cells.
AB  - Insulin-like growth factor binding protein-3, IGFBP-3, specifically binds to IGFs
      with high affinity, but it is also capable of modulating the IGF-I signalling
      pathway or inducing apoptosis independently of its binding to IGFs. The molecular
      mechanisms underlying the action of IGFBP-3 have not been elucidated. In this
      study, we have demonstrated that binding of IGFBP-3 to a cell surface receptor in
      MCF-7 breast carcinoma cells induces a rapid and transient increase in
      intracellular free calcium. This increase was mediated via a pertussis toxin
      sensitive pathway, indicating that the IGFBP-3 receptor may be specifically
      coupled to a Gi protein. The effect of IGFBP-3 on calcium concentrations was dose
      dependent and also occurred when IGFBP-3 was complexed with either IGF-I or
      heparin, suggesting that the receptor binding site is probably located in the
      least conserved central domain of IGFBP-3. Neither IGFBP-1, nor IGFBP-5
      (structurally the closest to IGFBP-3) altered intracellular calcium
      concentrations. These results provide evidence that a specific intracellular
      signal is triggered by IGFBP-3 binding to a cell surface receptor.

PMID- 12220678
TI  - Glycine 30 in iberiotoxin is a critical determinant of its specificity for maxi-K
      versus K(V) channels.
AB  - Iberiotoxin (IbTX) is a remarkably selective alpha-K toxin peptide (alpha-KTx)
      inhibitor of the maxi-K channel. In contrast, the highly homologous charybdotoxin
      inhibits both the maxi-K and K(V)1.3 channels with similar high affinity. The
      present study investigates the molecular basis for this specificity through
      mutagenesis of IbTX. The interactions of mutated peptides with maxi-K and K(V)1.3
      channels were monitored through dose-dependent displacement of specifically bound
      iodinated alpha-KTx peptides from membranes expressing these channels. Results of
      these studies suggest that the presence of a glycine at position 30 in IbTX is a
      major determinant of its specificity while the presence of four unique acidic
      residues in IbTX is not.

PMID- 12220679
TI  - The regions of securin and cyclin B proteins recognized by the ubiquitination
      machinery are natively unfolded.
AB  - The proteins securin and cyclin B are destroyed in mitosis by the
      ubiquitin/proteasome system. This destruction is important to mitotic
      progression. The N-terminal regions of these proteins contain the sequence
      features recognized by the ubiquitination system. We have demonstrated using
      circular dichroism and 1-D and 2-D nuclear magnetic resonance that these rather
      substantial regions are natively unfolded. Based on these findings, we propose a
      model that helps to explain previously enigmatic observations.

PMID- 12220680
TI  - Ectodomain shedding of furin: kinetics and role of the cysteine-rich region.
AB  - Furin, a member of the subtilisin-like pro-protein convertase family, is a type I
      membrane protein that undergoes ectodomain shedding. Metabolic labeling of cells
      stably expressing furin demonstrated that the shed form of furin is detected
      after 30 min. Moreover, sequence analysis revealed that specific residues of the
      cysteine-rich region of furin aligned with those of tumor necrosis factor
      receptor, which is also shed. Introduction within furin's cysteine-rich region of
      mutations that impair TNFR1 shedding also abolished furin shedding. Our results
      show that shedding of furin occurs rapidly and further suggest that specific
      cysteine residues may impart a conformation to the enzyme, thereby affecting its
      susceptibility to proteolysis.

PMID- 12220681
TI  - The Tzs protein from Agrobacterium tumefaciens C58 produces zeatin riboside 5'
      phosphate from 4-hydroxy-3-methyl-2-(E)-butenyl diphosphate and AMP.
AB  - The plant pathogen Agrobacterium tumefaciens produces cytokinins upon induction
      of the virulence genes by secondary metabolites from wounded plants, and these
      hormones are believed to stimulate the infection process. To study the
      biosynthetic pathway, the tzs gene, encoding the Tzs (trans-zeatin-synthesizing)
      protein from A. tumefaciens, was cloned and the protein was overproduced and
      purified. Analysis of its reactivity with radioactively labeled substrate
      demonstrated conversion of 4-hydroxy-3-methyl-2-(E)-butenyl diphosphate, a
      product of the deoxyxylulose phosphate pathway, with AMP to zeatin riboside 5'
      phosphate. This suggests that A. tumefaciens uses an alternative pathway of
      cytokinin biosynthesis, which had previously been hypothesized to operate in
      plants.

PMID- 12220682
TI  - Posttranslational modification of E. coli histone-like protein H-NS and bovine
      histones by short-chain poly-(R)-3-hydroxybutyrate (cPHB).
AB  - Short-chain poly-(R)-3-hydroxybutyrate (cPHB), a highly flexible, amphiphilic
      molecule with salt-solvating properties, is a ubiquitous constituent of
      prokaryotic and eukaryotic cells, wherein it is mainly conjugated to proteins.
      The solvating properties and cellular distribution of cPHB suggest it may be
      associated with proteins that bind and/or transfer DNA. Here we examine
      Escherichia coli protein H-NS and calf thymus histones, H1, H2A, H2B, H3, and H4,
      for the presence of cPHB. The proteins are related in that all bind to DNA and
      are implicated in the compact organization of the chromosome. The presence of
      cPHB in E. coli H-NS was first detected in Western blots of two-dimensional
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels of total cell
      proteins, probed with anti-cPHB IgG, and then by Western blot analysis of the
      purified protein. Western blot analysis of the calf thymus histones indicated
      that each contained cPHB. The presence of cPHB in H-NS and histones was confirmed
      by chemical assay. The in vivo size of conjugated cPHB could not be established
      due to the lack of standards and degradation of cPHB during protein purification
      and storage. The molecular characteristics of cPHB and its presence in histone
      like and histone proteins of diverse organisms suggest it may play a role in DNA
      binding and/or DNA organization.

PMID- 12220683
TI  - The YHR076w gene encodes a type 2C protein phosphatase and represents the seventh
      PP2C gene in budding yeast.

PMID- 12220684
TI  - Template switching generated during reverse transcription?

PMID- 12220685
TI  - Thrombolytic therapy after intraventricular hemorrhage: do we know enough?

PMID- 12220686
TI  - The role of antibodies in myasthenia gravis.
AB  - Myasthenia gravis is an autoimmune disease associated with antibodies directed to
      the postsynaptic acetylcholine receptor. These antibodies reduce the number of
      receptors. Autoantibodies against AChR and other muscle antigens can be used for
      the diagnosis of myasthenia gravis and related disorders. The origin and the role
      of these antibodies in the disease are discussed. Experimental autoimmune
      myasthenia gravis, an experimental model closely mimicking the disease, has
      provided answers to many questions about the role of antibodies, complement
      macrophages and AChR anchor proteins. Genetically modified anti-AChR antibodies
      may also be used in the future to treat myasthenia.

PMID- 12220687
TI  - The role of macrophage/microglia and astrocytes in the pathogenesis of three
      neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple
      sclerosis.
AB  - Macrophage/microglia (M phi) are the principal immune cells in the central
      nervous system (CNS) concomitant with inflammatory brain disease and play a
      significant role in the host defense against invading microorganisms. Astrocytes,
      as a significant component of the blood-brain barrier, behave as one of the
      immune effector cells in the CNS as well. However, both cell types may play a
      dual role, amplifying the effects of inflammation and mediating cellular damage
      as well as protecting the CNS. Interactions of the immune system, M phi, and
      astrocytes result in altered production of neurotoxins and neurotrophins by these
      cells. These effects alter the neuronal structure and function during
      pathogenesis of HIV-1-associated dementia (HAD), Alzheimer disease (AD), and
      multiple sclerosis (MS). HAD primarily involves subcortical gray matter, and both
      HAD and MS affect sub-cortical white matter. AD is a cortical disease. The
      process of M phi and astrocytes activation leading to neurotoxicity share
      similarities among the three diseases. Human Immunodeficiency Virus (HIV)-1
      infected M phi are involved in the pathogenesis of HAD and produce toxic
      molecules including cytokines, chemokines, and nitric oxide (NO). In AD, M phis
      produce these molecules and are activated by beta-amyloid proteins and related
      oligopeptides. Demyelination in MS involves M phi that become lipid laden,
      spurred by several possible antigens. In these three diseases, cytokine/chemokine
      communications between M phi and astrocytes occur and are involved in the balance
      of protective and destructive actions by these cells. This review describes the
      role of M phi and astrocytes in the pathogenesis of these three progressive
      neurological diseases, examining both beneficent and deleterious effects in each
      disease.

PMID- 12220688
TI  - Practice variation among Michigan neurologists in the use of intravenous heparin.
AB  - BACKGROUND/OBJECTIVE: The indications for intravenous (IV) heparin use in acute
      ischemic stroke are uncertain. We sought to determine the current practice
      patterns of neurologists in Michigan with regard to IV heparin use, in view of
      the fact that several major multi-center trials evaluating heparin and related
      compounds have been completed in the last decade. METHODS: A survey was conducted
      of 180 active, practicing neurologists in Michigan. Five clinical scenarios were
      included and factors influencing heparin use were also determined. RESULTS: The
      vast majority of neurologists in Michigan would use IV heparin for patients with
      atrial fibrillation-related stroke (91% of those with a defined opinion). Heparin
      use was also popular for stroke-in-evolution (77%). There was a lesser degree of
      heparin use for patients with more than one transient ischemic attack (49%) or
      for patients with stroke and normal cardiac rhythm. Medicolegal factors at least
      sometimes influenced the selection of heparin as a therapy for 41% of physicians.
      CONCLUSIONS: Despite recent clinical trial data on heparin and related compounds
      which for the most part has been negative, IV heparin use remains popular for
      certain clinical scenarios, especially acute stroke with atrial fibrillation.
      Further studies are necessary to determine whether negative clinical trials have
      the same impact on neurologist behavior as positive studies.

PMID- 12220689
TI  - New onset seizures in HIV-infected patients without intracranial mass lesions or
      meningitis--a clinical, radiological and SPECT scan study.
AB  - Fifteen HIV-infected patients who presented with new onset seizures (NOS) as the
      sole neurological manifestation, in whom no cause for the seizure was
      identifiable, were studied. The patients were mainly female with an average age
      of 31.3 years. They had generalised new onset seizures with a latency of 1.6
      months between the discovery of the HIV positivity and the onset of the seizure.
      The neurological examinations were normal with no dementia. The
      electroencephalographic examinations were either normal or there was a
      generalised epileptic disturbance (GED). The patients have AIDS defining CD4+ T
      lymphocyte cell counts. There was a high prevalence of pulmonary tuberculosis
      (PTB) or multiple non-neurological illnesses in our study group. They have normal
      cerebrospinal fluid (CSF) analysis except for the presence of the HIV virus. All
      the patients have normal computerised tomogram (CT)/magnetic resonance imaging
      (MRI) scans of the brain. All the patients studied have abnormal right or left
      temporal lobe perfusion defects on the SPECT scan studies of the brain. The
      findings suggest that the new onset seizures in the HIV-infected patients are
      associated with direct HIV infection. The SPECT scan findings suggest that the
      HIV virus induce a focal metabolic abnormality or encephalopathy. The new onset
      seizure is then the manifestation of this abnormality.

PMID- 12220690
TI  - Tissue plasminogen activator for the treatment of intraventricular hematoma: the
      dose-effect relationship.
AB  - In this study, we investigated the dose-effect relationship and safety of tissue
      plasminogen activator (tPA) for the treatment of intraventricular
      hemorrhage/hematoma (IVH) in rats. Adult male Sprague-Dawley rats were injected
      with autologous blood into the left lateral ventricle to establish IVH. Two hours
      later, Ringer's saline or 0.25-2 microg of tPA were administered directly to the
      IVH over 3 h. The regional cerebral blood flow (rCBF) on the surface of the left
      parietal cortex was measured with laser Doppler flowmetry. Twenty-four hours
      after the build-up of IVH, the brains were removed for morphometrical and
      histological studies. A dose of 0.5-2 microg tPA significantly diminished the IVH
      in a dose-dependent manner (p < 0.001). However, only the dose of 0.5 microg tPA
      significantly ameliorated the reduction of rCBF 24 h after IVH (p < 0.01). TPA
      did not improve the ventricular dilatation on the side with IVH. Instead, 1-2
      microg of tPA caused additional injuries, including intraventricular leukocytosis
      and edema of periventricular tissues and choroid plexus on both hemispheres.
      These results indicate that higher doses of tPA may have detrimental effects on
      the brain. The dosage rate of 0.5 microg seems beneficial to treat 5 microl of
      IVH (equals to a dose of 0.1 mg/ml blood) in our model in terms of the
      satisfactory fibrinolysis and less damage to the brain.

PMID- 12220691
TI  - "Supplementary motor area (SMA) seizure" rather than "SMA epilepsy" in optimal
      surgical candidates: a document of subdural mapping.
AB  - PURPOSE: To clarify the relationship between epileptogenic zone and supplementary
      motor area (SMA) in patients who were regarded as the optimal surgical candidates
      for their intractable SMA seizures. METHODS: We analyzed the epileptogenic zone
      at/or adjacent to the SMA in four patients with clinical SMA seizures. All four
      patients had noninvasive presurgical evaluations (long-term video/EEG monitoring,
      MRI, and neuroimaging with radioisotopes), which provided convergent results
      between ictal semiology and the epileptogenic area, and thus, they had
      chronically implanted subdural electrodes, and finally had focus resection with a
      follow-up period of more than 2 years. RESULTS: Three patients had lesions shown
      by MRI outside the SMA, and one patient had a lesion within the SMA. Interictal
      epileptiform discharges were seen at/or outside the SMA. Ictal EEG pattern
      originated from the SMA in one patient, from the high lateral frontal area in two
      patients, and from the precuneus in one patient. In the latter three patients,
      the ictal EEG pattern immediately spread to the SMA. Those ictal onset zones were
      consistently localized within/or just adjacent to the lesions revealed by MRI.
      Only one patient had SMA resection, and three had the resection of epileptogenic
      zone by preserving the SMA. No neurological deficits developed and good seizure
      control was achieved. CONCLUSION: Among surgical candidates for intractable SMA
      seizures, frontal cortex other than SMA or even parietal cortex can be
      epileptogenic, and thus, the SMA itself may not necessarily have to be resected.
      This notion is clinically important when selecting surgical candidates as well as
      when planning presurgical invasive evaluation in patients with intractable SMA
      seizures.

PMID- 12220692
TI  - High early case fatality after ischaemic stroke in Poland: exploration of
      possible explanations in the International Stroke Trial.
AB  - PURPOSE: To determine why Polish patients included in the International Stroke
      Trial (IST) had a higher early case fatality than patients from other countries.
      METHODS: Of 19,435 patients randomised to IST, 17,370 had CT or autopsy-confirmed
      ischaemic stroke. We compared the baseline clinical state and 14-day case
      fatality of patients randomised in Polish centres with those from all other IST
      countries. We examined: age, gender, presence of atrial fibrillation (AF),
      conscious level, neurological deficit, cause of death and aspirin use in the 3
      days before stroke. RESULTS: In Poland, the 14-day case fatality rate was
      significantly higher than in other IST countries (13% vs. 9.6%; odds ratio, OR,
      1.5, 95% confidence interval, CI, 1.2-1.9). In Poland, a significantly higher
      proportion of deaths was attributed to coronary heart disease (2.5% vs. 0.7%) and
      pulmonary embolism (1.0% vs. 0.4%). Polish patients had higher percentage of AF
      and drowsiness, but were younger. When these factors were adjusted for, Polish
      patients still had approximately a 57% higher risk of death within 14 days
      compared with other countries. A logistic regression analysis revealed that an
      increased risk of death within 14 days in Poland compared to other IST patients
      was present among patients younger than 75 years (OR 1.7; 95% CI 1.3-2.4),
      females (OR 1.8; 95% CI 1.3-2.5), patients who were alert at onset (OR 2.4; 95%
      CI 1.7-3.4), with partial anterior circulation syndrome (PACS) (OR 2.0; 95% CI
      1.4-2.8) or lacunar syndrome (LACS) (OR 2.4; 95% CI 1.1-5.0) and without AF (OR
      1.8; 95% CI 1.3-2.4). Polish patients were less likely to have been on aspirin
      before their stroke than other countries (7.6% vs. 20.8%). CONCLUSION: The 14-day
      case fatality was significantly higher in Poland than in other countries in IST.
      Part of the increase was due to greater stroke severity in the Polish patients.
      However, differences persisted even after adjustment for baseline stroke
      severity. Several factors may have contributed the excess: poor attention to
      treatment of cardiovascular disease, less attention to treatment of secondary
      complications of stroke and some other--as yet unidentified--factor specific to
      Poland.

PMID- 12220693
TI  - Movement disorders in hereditary ataxias.
AB  - Movement disorders are well known features of some dominant hereditary ataxias
      (HA), specially SCA3/Machado-Joseph disease and dentatorubropallidolusyan
      atrophy. However, little is known about the existence and classification of
      movement disorders in other dominant and recessive ataxias. We prospectively
      studied the presence of movement disorders in patients referred for HA over the
      last 3 years. Only those patients with a confirmed family history of ataxia were
      included. We studied 84 cases of HA, including 46 cases of recessive and 38 cases
      of dominant HA. Thirty out of 46 cases of recessive HA could be classified as:
      Friedreich ataxia (FA), 29 cases; vitamin E deficiency, 1 case. Twenty-three out
      of 38 cases of dominant HA could be classified as: SCA 2, 4 cases; SCA 3, 8
      cases; SCA 6, 4 cases; SCA 7, 6 cases and SCA 8, 1 case. We observed movement
      disorders in 20/38 (52%) patients with dominant HA and 25/46 (54%) cases with
      recessive HA, including 16 patients (16/29) with FA. In general, postural tremor
      was the most frequent observed movement disorder (27 cases), followed by dystonia
      (22 cases). Five patients had akinetic rigid syndrome, and in 13 cases, several
      movement disorders coexisted. Movement disorders are frequent findings in HA, not
      only in dominant HA but also in recessive HA.

PMID- 12220694
TI  - Hyperhomocysteinemia in Japanese patients with convalescent stage ischemic
      stroke: effect of combined therapy with folic acid and mecobalamine.
AB  - Hyperhomocysteinemia is considered to be a risk factor for vascular diseases
      including ischemic stroke. It has been shown that plasma homocysteine level can
      be lowered by folic acid supplementation. Vitamin B(12) may be also beneficial
      when included in the supplement regimen with folic acid. We have examined in
      Japanese patients with ischemic stroke the homocysteine-lowering potential of a
      combination therapy with folic acid and vitamin B(12). Patients with ischemic
      stroke were randomized into three groups and each group received vitamin B(12)
      (1500 microg/day, n = 63), folic acid (5 mg/day, n = 64), or both vitamin B(12)
      and folic acid (n = 64) for 8 weeks. Plasma levels of homocysteine and these
      vitamins were followed. Significant reduction in plasma homocysteine was observed
      in all three groups, and the combination therapy yielded the most remarkable
      result, i.e., plasma total homocysteine was reduced by 38.5% and this was
      significantly larger than the reduction in other two groups (22.4% and 10.9% in
      the groups received folic acid and vitamin B(12), respectively). Vitamin B(12)
      synergizes with folic acid in reducing plasma homocysteine in Japanese patients
      with ischemic stroke and the combined therapy may be particularly effective in
      the secondary prevention.

PMID- 12220695
TI  - Treatment of the chronic inflammation in peripheral target tissue improves the
      crushed nerve recovery in the rat: histopathological assessment of the nerve
      recovery.
AB  - An experimental study was performed to investigate the influence of subsidence of
      chronic inflammation in peripheral target tissue on the recovery of crushed
      nerve. Seventy-eight male Wistar rats weighing 300-370 g were used. The sciatic
      nerve was operatively crushed unilaterally with an aneurysm clip (250 gf) applied
      for 5 min. Chronic inflammation, localized to the ankle, was induced by intra
      articular injection of complete Freund's adjuvant 1 week preoperatively.
      Prednisolone farnesylate (PNF-21) 1.4% gel was applied on the ankle as an anti
      inflammatory agent for consecutive days after the operation. The animals were
      divided into five groups as follows: crush injury with ipsilateral arthritis
      (CIA); crush injury with ipsilateral arthritis and PNF-21 gel applied on the
      ipsilateral ankle (CIA + IPNF); crush injury with ipsilateral arthritis and PNF
      21 gel applied on the contralateral ankle (CIA + CPNF); crush injury with
      contralateral arthritis (CCA); crush injury without arthritis (C). Specimens for
      histopathological examination were taken from the nerve at a site 5 mm distal to
      the crush lesion at 4 weeks postoperatively. The average axon diameter was
      significantly larger in the CIA + IPNF group than in the CIA group (p < 0.01). No
      significant difference was observed between the CIA + CPNF group and the CIA
      group. In conclusion, chronic inflammation in peripheral target tissue suppresses
      recovery of the crushed nerve, and subsidence of this chronic inflammation
      improves this suppression histopathologically.

PMID- 12220696
TI  - Activation of the tissue kallikrein-kinin system in stroke.
AB  - Edema formation is a major problem in large ischemic infarcts, and the underlying
      breakdown of the blood-brain barrier is only incompletely understood. Here, we
      report that the tissue kallikrein-kinin system, which influences the permeability
      of the blood-brain barrier, is activated in stroke. In 22 patients with large
      infarcts in the territory of the middle cerebral artery, we found elevated plasma
      concentrations of the tissue kinin kallidin. The data suggest that further
      studies on a possible role of kinin receptor antagonists on edema after stroke
      are warranted.

PMID- 12220697
TI  - In myasthenia gravis, clinical and immunological improvement post-thymectomy
      segregate with results of in vitro antibody secretion by immunocytes.
AB  - In myasthenia gravis (MG), presence of pathogenic acetylcholine receptor
      antibodies (AchRAb) and thymic pathology are related. Our study assesses the long
      term clinical outcome of thymectomy as a function of thymic pathologies, AchRAb
      levels in blood and the ability of immunocytes to secrete AchRAb ex vivo. We
      found that those patients who have thymocytes that secrete AchRAb in vitro have a
      greater decrease in their need for Mestinon over the 60 months of follow-up than
      the non-secretors (p = 0.04). Those patients whose cultured peripheral blood
      mononuclear cells (PBMC) secreted AchRAb also had a greater decrease in Mestinon
      requirements over the 60 months of follow-up than the non-secretors (p = 0.05),
      however, differences between the two groups at each individual assessment were
      not statistically significant. Serial post-op AchRAb measurements in sera of
      thymocyte and PBMC non-secretors showed no change from pre-op levels (< 10
      nmol/l), while secretors had a reduction of more than 80% from pre-op levels,
      starting 6 months post-op. We also found that results of PBMC culture at time of
      thymectomy is a better predictor of response to thymectomy than serum AchRAb
      levels but inferior to results of thymocytes cultures. Patients with thymoma had
      the highest proportion of individuals secreting AchRAb from thymocytes in culture
      (78%), the shortest duration of disease (9 months) and showed the greatest trend
      toward improvement in clinical signs and symptoms post-op. We have thus
      demonstrated the long held suspicion that removal of actively secreting cells
      from the thymus at an early time in the disease confers the greatest benefit.

PMID- 12220698
TI  - Evidence and age-related distribution of mtDNA D-loop point mutations in skeletal
      muscle from healthy subjects and mitochondrial patients.
AB  - The progressive accumulation of mitochondrial DNA (mtDNA) alterations, ranging
      from single mutations to large-scale deletions, in both the normal ageing process
      and pathological conditions is a relevant phenomenon in terms of frequency and
      heteroplasmic degree. Recently, two point mutations (A189G and T408A) within the
      Displacement loop (D-loop) region, the control region for mtDNA replication, were
      shown to occur in skeletal muscles from aged individuals. We evaluated the
      presence and the heteroplasmy levels of these two mutations in muscle biopsies
      from 91 unrelated individuals of different ages (21 healthy subjects and 70
      patients affected by mitochondrial encephalomyopathies). Overall, both mutations
      significantly accumulate with age. However, a different relationship was
      discovered among the different subgroups of patients: a higher number of A189G
      positive subjects younger than 53 years was detected in the subgroup of multiple
      deleted patients; furthermore, a trend towards an increased risk for the
      mutations was evidenced among patients carrying multiple deletions when compared
      to healthy controls. These findings support the idea that a common biological
      mechanism determines the accumulation of somatic point mutations in the D-loop
      region, both in healthy subjects and in mitochondrial myopathy patients. At the
      same time, it appears that disorders caused by mutations of nuclear genes
      controlling mtDNA replication (the "mtDNA multiple deletions" syndromes) present
      a temporal advantage to mutate in the D-loop region. This observation may be
      relevant to the definition of the molecular pathogenesis of these latter
      syndromes.

PMID- 12220699
TI  - Interleukin-10 promoter polymorphisms in patients with multiple sclerosis.
AB  - The expression level of interleukin-10 (IL-10) is related to polymorphisms -1082
      (G/A), -819 (T/C) and -592 (A/C) in the promoter region of the IL-10 gene. The
      distribution of these polymorphisms was analyzed to determine whether they could
      influence disease susceptibility or clinical course in multiple sclerosis (MS).
      The -1082 (G/A), -819 (T/C) and -592 (A/C) genotypes were similarly distributed
      between MS patients and the controls. The primary progressive MS patients with
      the low IL-10 expression haplotype showed a trend towards a worse clinical
      outcome than did patients with medium- or high-expression haplotypes (P = 0.056).
      The polymorphisms did not influence the clinical course in patients with
      relapsing-remitting MS.

PMID- 12220702
TI  - Development of androgen receptor and p75(NTR) mRNAs and peptides in the lumbar
      spinal cord of the gerbil.
AB  - Development of sex differences in the spinal cord appears to be largely under the
      control of androgen and although neurotrophins may also have a role. Spinal cords
      of male and female neonatal gerbils (postnatal days 1, 5, 7, 10, 23) and adult
      gerbils (postnatal day 150) were examined to determine the relative temporal
      expression of androgen receptor (AR) and the low-affinity neurotrophin receptor
      (p75) mRNAs within the spinal nucleus of the bulbocavernosus (SNB) and
      dorsolateral nucleus (DLN). Furthermore, prepubertal male gerbils were placed
      into one of six gonadal hormone treatment groups at weaning: Either sham
      castrate, castrated with gonadal hormone replacement, or castrated without
      gonadal hormone replacement. Ten weeks later gerbils were aldehyde-perfused,
      spinal cords removed and processed for presence of AR and p75 immunoreactivity
      (ir) in motoneurons of the SNB and DLN. During neonatal development, there were
      significant increases in androgen receptor mRNA within the SNB and DLN. In the
      SNB, the increase in androgen receptor mRNA preceded the increase in p75 mRNA.
      Peripubertally, significantly more SNB than DLN motoneurons contained AR- and p75
      ir. These data demonstrate that AR expression occurs along the same developmental
      time frame as the development of the SNB and DLN and the organizational effects
      of androgens on their development continues through puberty in the male gerbil.

PMID- 12220704
TI  - Quantitative measurement of glutamate receptor subunit protein expression in the
      postnatal rat spinal cord.
AB  - Glutamate is the major excitatory neurotransmitter in the CNS and its effects on
      neurons are dependent on the type and composition of glutamate receptors with
      which it interacts. In this study, the protein expression levels of several
      ionotropic glutamate receptor subunits (N-methyl-D-aspartate (NMDA) subunits NR1,
      NR2A, NR2B, and alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA)
      receptor subunits GluR1, GluR2, GluR4) were quantified in particulate
      preparations from rat spinal cord at various ages after birth. We found that all
      six subunits showed high expression in the early postnatal period, followed by a
      subsequent decline as the rats matured to adults. The levels of two subunits
      (NR2A and GluR4) were found to initially increase during the first postnatal week
      prior to the decline to adult levels. The high levels of expression observed of
      these subunits in the early postnatal period may have implications for mechanisms
      of neural injury and cell death in the immature nervous system that involve
      cation influx through ionotropic glutamate receptors.

PMID- 12220703
TI  - Enhanced viability and neuronal differentiation of neural progenitors by
      chromaffin cell co-culture.
AB  - The transplantation of neural stem cells and progenitors has potential in
      restoring lost cellular populations following central nervous system (CNS) injury
      or disease, but survival and neuronal differentiation in the adult CNS may be
      insufficient in the absence of exogenous trophic support. Adrenal medullary
      chromaffin cells produce a trophic cocktail including basic fibroblast growth
      factor (FGF-2) and neurotrophins. The aim of this study was to evaluate whether
      chromaffin cells can provide a supportive microenvironment for neural progenitor
      cells. In order to assess this, the growth and differentiation of neural
      progenitor cell cultures from embryonic rat cortex were compared in standard FGF
      2-supplemented neural progenitor growth media, in standard media but lacking FGF
      2, or in media lacking FGF-2 but co-cultured with bovine chromaffin cells. Using
      bromodeoxyuridine (BrdU)-prelabeling, findings indicated poor survival of
      progenitor cultures in the absence of FGF-2. In contrast, the addition of
      chromaffin cells in co-culture appeared to 'rescue' the progenitor cultures and
      resulted in robust neurospheres containing numerous BrdU-labeled cells
      interspersed with and closely apposed to chromaffin cells. As indicated by H3
      labeling, cells in co-cultures continued to proliferate, but at a substantially
      reduced rate compared with standard FGF-2 supplemented growth media. The co
      cultures contained more beta-tubulin III-positive processes than parallel
      cultures maintained in FGF-2-supplemented media and these cells displayed a more
      mature phenotype with numerous varicosities and complex processes. These findings
      indicate that chromaffin cells can provide a supportive environment for the
      survival and neuronal differentiation of neural progenitor cells and suggest that
      their addition may be useful as a sustained source of trophic support to improve
      outcomes of neural stem cell transplantation.

PMID- 12220705
TI  - Serotonin transporter binding increases in caudate-putamen and nucleus accumbens
      after neonatal 6-hydroxydopamine lesions in rats: implications for motor
      hyperactivity.
AB  - We examined serotonin (5-HT) transporters in rat forebrain using quantitative
      autoradiography at three distinct developmental stages after neonatal 6
      hydroxydopamine lesions. The lesions substantially increased 5-HT transporter
      binding in both caudate-putamen and nucleus accumbens, but not cerebral cortex.
      The effects reached maximal levels as early as postnatal day (PD) 24, and were
      sustained until early adulthood. Behavioral analyses indicated that neonatal
      lesions resulted in motor hyperactivity on PD 24, but not on PD 36 or 59. These
      findings suggest that excess 5-HT transporters reflect serotonin hyperinnervation
      reported to occur in lesioned rats, and may modulate motor hyperactivity.

PMID- 12220706
TI  - Phosphorylation of glial fibrillary acidic protein is stimulated by glutamate via
      NMDA receptors in cortical microslices and in mixed neuronal/glial cell cultures
      prepared from the cerebellum.
AB  - In previous work we showed that phosphorylation of glial fibrillary acidic
      protein (GFAP), an astrocyte marker, is increased by glutamate in hippocampal
      slices from immature rats via a type II metabotropic receptor. In the present
      work we show that glutamate also stimulates GFAP phosphorylation in microslices
      prepared from immature cerebellar cortex, but by a different receptor mechanism
      from that observed in the hippocampus. Thus, in cerebellar microslices, NMDA
      consistently stimulated GFAP phosphorylation, whereas no effect of metabotropic
      or non-NMDA ionotropic agonists was observed. Glutamate and NMDA also stimulated
      GFAP phosphorylation in mixed neuronal/glial cell cultures from the cerebellum,
      although no effect of these agonists was observed in primary cultures of
      cerebellar astrocytes. In both models, the effects of glutamate and NMDA were
      dependent on external Ca(2+), were reversed by the NMDA receptor antagonist AP5
      and were not blocked by tetrodotoxin. In the slice study the effect of NMDA was
      confined to a period starting with the first detectable expression of GFAP at 10
      days and finishing at 16 days postnatal, as previously observed with metabotropic
      agonists in hippocampal slices. This period in the rat corresponds to the start
      of synaptogenesis when astrocyte hypertrophy is occurring. The results are
      discussed in the light of information in the literature on the occurrence of
      functional NMDA receptor subunits in glia.

PMID- 12220707
TI  - Postnatal regulation of ZnT-1 expression in the mouse brain.
AB  - We have characterized the postnatal development of ZnT-1, a putative zinc
      transporter, in the mouse brain with respect to chelatable zinc in four distinct
      brain areas: cerebral cortex, hippocampus, olfactory bulb and cerebellum. At
      birth, both zinc and ZnT-1 immunoreactivity were nearly undetectable. Beginning
      at the end of the first postnatal week, ZnT-1 expression increased significantly
      in all areas examined except the cerebellum, which contains virtually no synaptic
      zinc. Moreover, neurons immunoreactive for ZnT-1 were typically present in areas
      rich in synaptic zinc, which increased in parallel with ZnT-1. In the cerebellum,
      in contrast, Purkinje cells exhibited robust immunoreactivity for ZnT-1 only in
      the second postnatal week. While the parallel development of zinc and ZnT-1 in
      forebrain regions supports a direct role for synaptic zinc in regulating ZnT-1
      expression, ZnT-1 in cerebellar Purkinje cells could indicate that expression of
      this zinc transporter may also be regulated by a non-synaptic pool of zinc or by
      other mechanism(s). The striking developmental regulation of ZnT-1 expression
      together with synaptic zinc indicates that ZnT-1 may play a key role in
      protecting developing neurons against potentially toxic zinc.

PMID- 12220708
TI  - Altered whisker patterns induced by ectopic expression of Shh are topographically
      represented by barrels.
AB  - Barrels in the somatosensory cortex are segregated columns, which somatotopically
      relate to facial whiskers. The barrel pattern is assumed to be determined by an
      extrinsic mechanism (the domino theory). This theory is based on whisker lesion
      experiments and developmental observations regarding the serial establishment of
      the somatotopic pattern in which pattern formations are relayed from the
      periphery to the central nervous system. However, the barrel pattern is possibly
      determined by an intrinsic mechanism, especially in its primitive form. In order
      to investigate the definitive mechanism, we established an experimental system in
      which the cortical barrel pattern can be altered, not by using a lesion paradigm,
      but by epigenetically changing the whisker pattern. Sonic hedgehog (Shh) plays a
      pivotal role in whisker development. We transfected an adenovirus harboring
      chicken Shh (Ad-cShh) to mouse embryos (E9.5-E11.5) using an in utero surgical
      technique. When Ad-cShh was expressed in the epidermis, Bmp4, Ptch, Ptch2 and
      Gli1 were induced ectopically in the interfollicular region. In contrast, the
      expression of Bmp2 and Shh itself was unaltered. At a suitable dose of Ad-cShh,
      some pups displayed supernumerary whiskers or a disordered whisker pattern. The
      barrel patterns of these mice after the critical period were topographic
      representations of the contralateral side of the new whisker patterns when
      visualized by a cytochrome oxidase or Nissle staining method, supporting the
      instructive role of the extrinsic mechanism.

PMID- 12220709
TI  - An overview of toxins and genes from the venom of the Asian scorpion Buthus
      martensi Karsch.
AB  - Among the different scorpion species, Buthus martensi Karsch (BmK), a widely
      distributed scorpion species in Asia, has received a lot of attention. Indeed,
      over the past decade, more than 70 different peptides, toxins or homologues have
      been isolated and more peptides are probably still to be revealed. This review is
      focusing on the many peptides isolated from the venom of this scorpion, their
      targets, their genes and their structures. The aim is to give both a 'state of
      the art' view of the research on BmK venom and an illustration of the complexity
      of this scorpion venom. In the present manuscript, we have listed the different
      ion channel toxins and homologues isolated from the venom of BmK, either from the
      literature or from databases. We have described here 51 long-chain peptides
      related to the Na(+) channel toxins family: 34 related to the alpha-toxin family,
      four related to the excitatory insect toxin family, 10 related to the depressant
      insect toxin, one beta-like toxin plus two peptides, BmK AS and AS1, that act on
      ryanodine receptors. We also listed 18 peptides related to the K(+) channel toxin
      family: 14 short chain toxins or homologues, two long chain K(+) toxin homologues
      and two putative K(+) toxin precursors. Additionally, two chlorotoxin like
      peptides (Bm-12 and 12 b) have been isolated in the venom of BmK. Besides these
      ion channels toxins, two peptides without disulfide bridges (the bradykinin
      potentiating peptide BmK bpp and BmK n1) and three peptides with no known
      functions have also been discovered in this venom. We have also taken the
      opportunity of this review to update the classification of scorpion K(+) toxins
      () which now presents 17 subfamilies instead of the 12 described earlier. The
      work on the venom of BmK led to the discovery of two new subfamilies, alpha-KT x
      14 and alpha-KT x 17.

PMID- 12220711
TI  - Novel electrochemical immunosensors for seafood toxin analysis.
AB  - The current work describes the optimisation of a screen-printed electrode (SPE)
      system for measurement of a variety of seafood toxins, such as okadaic acid,
      brevetoxin, domoic acid and tetrodotoxin. A disposable screen-printed carbon
      electrode coupled with amperometric detection of p-aminophenol at +300 mV vs.
      Ag/AgCl, produced by the label, alkaline phosphatase, was used for signal
      measurement. ELISA was primarily used to develop all toxin systems, prior to
      transferring to SPE. The sensors incorporate a relevant range for toxin
      detection, by which humans become ill, with detection limits achieved at SPE to
      the order of ng ml (-1) (ppb) or lower in some cases. The SPE system is simple
      and cost-effective due to their disposable nature, and analysis time is complete
      in 30 min. In addition, analyses can be achieved outside of a laboratory
      environment allowing for in-field measurements. Recovery experiments on selected
      toxins using the relevant working ranges highlighted the functionality of these
      systems yielding a +/-10% deviation for the true value.

PMID- 12220710
TI  - Emerita analoga (Stimpson)--possible new indicator species for the phycotoxin
      domoic acid in California coastal waters.
AB  - Blooms of domoic acid (DA) synthesizing diatoms (Pseudo-nitzschia spp.) have been
      associated with the death and injury of hundreds of marine shorebirds and
      mammals, exposed humans to potentially serious health risks, and threatened to
      significantly impact coastal fisheries and commerce dependent on marine
      resources. While indicator organisms are widely utilized to monitor for marine
      biotoxins like paralytic shellfish poisoning toxins, a reliable intertidal
      indicator species to monitor DA remains to be identified. Here we evaluate and
      confirm the utility of the common sand crab (Emerita analoga) as an indicator for
      DA in comparison with sea mussels (Mytilus californianus). Mussels and sand
      crabs, collected from natural populations in Santa Cruz, California (April 1999
      February 2000), were tested for DA using the HPLC-UV method. Toxin loads in sand
      crabs ranged from below detectable limits to 13.4 micro g DA g(-1) and coincided
      with the abundance of DA producing Pseudo-nitzschia species nearshore. Toxin
      levels in mussels collected during the study period were below HPLC-UV detectable
      limits. The rise and fall of DA in sand crabs in synchrony with Pseudo-nitzschia
      abundance, combined with this common intertidal species' accessibility and ease
      of DA extraction, clearly indicate the utility of sand crabs as a reliable, cost
      effective monitoring tool for DA in the nearshore coastal environment.

PMID- 12220712
TI  - Cysteine proteinase inhibitors in elapid and hydrophiid snake venoms.
AB  - The ability of elapid and hydrophiid snake venoms to inhibit cathepsin L was
      tested. All nine species of elapid and three species of hydrophiid snake venoms
      tested showed inhibition against cathepsin L. All of these venoms tested also
      showed inhibition against papain as well as against cathepsin L. Among these
      venoms, two elapid (Laticauda semifasciata venom, and Ophiophagus hannah venom)
      and one hydrophiid snake venom (Notechis scutatus scutatus venom) showed strong
      inhibition against both cathepsin L and papain. These venoms contained 12.0-13.0
      kDa low molecular-weight cysteine proteinase inhibitors.

PMID- 12220713
TI  - Neuromuscular action of Bothrops lanceolatus (Fer de lance) venom and a
      caseinolytic fraction.
AB  - A protein capable of inducing neuromuscular blockade in avian preparations and of
      depolarizing mouse diaphragm muscle was isolated from Bothrops lanceolatus venom
      using gel filtration and ion-exchange chromatography. The purified protein was a
      single chain polypeptide with an estimated molecular mass of 27.5 kDa by SDS-PAGE
      and had caseinolytic activity (13.3 units/mg), but no phospholipase A(2).
      B.lanceolatus venom (50 micro g/ml) and the caseinolytic protein (20 micro g/ml)
      produced contracture and progressive irreversible blockade (50% in 25+/-5 min
      (SEM) and 45+/-15 min, respectively), in indirectly stimulated chick biventer
      cervicis preparations. The contractile responses to acetylcholine (ACh; 37 and 74
      micro M, n=6) were inhibited by venom and the caseinolytic protein, whereas those
      to potassium (13.4mM, n=6) were not. Membrane resting potential measurements in
      mouse hemidiaphragm preparations showed that B.lanceolatus venom and the purified
      protein caused depolarization which was prevented by D-tubocurarine (14.6mM). The
      venom produced a slight increase in the amplitude and frequency of miniature end
      plate potentials, but this effect was not seen with the purified fraction. These
      results suggest that the purified protein acts exclusively post-synaptically.

PMID- 12220714
TI  - Russell's viper snakebite in Taiwan: differences from other Asian countries.
AB  - Formosan Russell's viper (Daboia russelli siamensis) is the sixth most frequent
      cause of snakebite in Taiwan. Its venom has been thought to have both neurotoxic
      and hematoxic properties. This viper's snakebite is rare and thus scarcely
      subjected to systemic studies. In this paper, we retrospectively analyzed and
      described 18 cases of viper snakebite from 1987 to 1999. Like that of the
      Russell's viper snakebite in other South East Asian areas, varied degrees of
      acute renal failure, incoagulable blood with bleeding diathesis and hemolysis
      were the major symptoms found in the systemic envenoming patients. Systemic
      thrombosis seems to be the distinguishing feature in Formosan Russell's viper
      snakebite. Neither symptoms nor signs of neuromuscular junction blocking effects
      were observed, which is another difference from symptoms observed after bites of
      some other Russell's viper subspecies, suggesting a significant geographic
      variation. These findings confirmed the clinical importance of Russell's viper
      snakebite in Taiwan.

PMID- 12220715
TI  - Apparent membrane pore-formation by Portuguese Man-of-war (Physalia physalis)
      venom in intact cultured cells.
AB  - Intracellular, ratiometric microfluorimetry with fura-2 reveals that low doses of
      Portuguese Man-of-war (Physalia physalis) venom cause a linear increase in
      intracellular calcium accumulation by cultured L-929 cells. The influx of calcium
      is preceded by a lag period that is relatively independent of venom
      concentration, except at very low concentrations. Electron micrographs of
      negatively stained preparations of membranes from venom-treated L-929 and
      GH(4)C(1) cells exhibit 10-80 nm diameter lesions. The number and diameter of
      these lesions correlate with venom concentration. The venom forms lesions in
      GH(4)C(1) cells at much lower concentrations than in L-929 cells. Osmotic
      protectants such as sucrose and polyethylene glycol (PEG), reduce the extent of
      lactate dehydrogenase (LDH) release from venom-treated cells with the higher
      molecular weight PEG causing a greater inhibition of LDH release than sucrose.
      These results imply that Man-of-war venom produces pore-like structures in the
      membranes of target cells, which leads to colloid osmotic swelling with
      subsequent release of intracellular proteins and cell lysis.

PMID- 12220716
TI  - Purification, characterization and crystallization of Jararacussin-I, a
      fibrinogen-clotting enzyme isolated from the venom of Bothrops jararacussu.
AB  - A fibrinogen-clotting enzyme, Jararacussin-I, was purified from the venom of
      Bothrops jararacussu by a combination of ion exchange chromatography using
      Resource 15S resin and affinity chromatography using Benzamidine Sepharose 6B
      resin. Jararacussin-I displays a molecular mass of 28 kDa as estimated by sodium
      dodecyl sulphate-PAGE and possesses an isoelectric point of 5.0. The coagulant
      specific activity of the enzyme was determined to be 45.8 NIHU/mg using bovine
      fibrinogen as the substrate and the esterase specific activity was determined to
      be 258.7 U/mg. The protease inhibitors, benzamidine and DTT inhibited the
      esterase specific activity by 72.4 and 69.7%, respectively. The optimal
      temperature and pH for the degradation of both chains of fibrinogen and esterase
      specific activity were determined to be 37 degrees C and 7.4-8.0, respectively.
      The enzyme was inactivated at both 4 and 75 degrees C. Single crystals of
      Jararacussin-I were obtained and complete three-dimensional X-ray diffraction
      data was collected at the Brazilian National Synchrotron Source (LNLS) to a
      resolution of 2.4A.

PMID- 12220717
TI  - Characterization and cloning of a novel phospholipase A(2) from the venom of
      Trimeresurus jerdonii snake.
AB  - A phospholipase A(2) (PLA(2)), called jerdoxin, was isolated from Trimeresurus
      jerdonni snake venom and partially characterized. The protein was purified by
      three chromatographic steps. SDS-polyacrylamide gel electrophoresis in the
      presence or absence of dithiothreitol showed that it had a molecular mass of 15
      kDa. Jerdoxin had an enzymatic activity of 39.4 micro mol/min/mg towards egg yolk
      phosphatidyl choline (PC). It induced edema in the footpads of mice. In addition,
      jerdoxin exhibited indirect hemolytic activity. About 97% hemolysis was observed
      when 2 micro g/ml enzyme was incubated for 90 min in the presence of PC and
      Ca(2+). No detectable hemolysis was noticed when PC was not added. Ca(2+) was
      necessary for jerdoxin to exert its hemolytic activity, since only 52% hemolysis
      was seen when Ca(2+) was absent in the reaction mixture. Furthermore, jerdoxin
      inhibited ADP induced rabbit platelet aggregation and the inhibition was dose
      dependent with an IC(50) of 1.0 micro M. The complete amino acid sequence of
      jerdoxin deduced from cDNA sequence shared high homology with other snake venom
      PLA(2)s, especially the D 49 PLA(2)s. Also, the residues concerned to Ca(2+)
      binding were conserved. This is the first report of cDNA sequence of T. jerdonii
      venom PLA(2).

PMID- 12220718
TI  - Complex toxin profiles in phytoplankton and Greenshell mussels (Perna
      canaliculus), revealed by LC-MS/MS analysis.
AB  - Toxin profiles were determined in phytoplankton cell concentrates and Greenshell
      mussels (Perna canaliculus) exposed to a dinoflagellate bloom dominated by
      Dinophysis acuta and Protoceratium reticulatum. This was achieved by using a
      method for the simultaneous identification and quantification of a variety of
      micro-algal toxins by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      with electrospray ionisation (+/-) and monitoring of daughter ions in multiple
      reaction modes. Plankton concentrates and shellfish contained high levels of
      yessotoxins (YTXs) and pectenotoxins (PTXs) and low levels of okadaic acid (OA).
      A high proportion (>87%) of the OA in both plankton and shellfish was released by
      alkaline hydrolysis. An isomer of pectenotoxin 1 (PTX1i) was nearly as abundant
      as pectenotoxin 2 (PTX2) in the plankton and shellfish, and the latter contained
      high levels of their respective seco acids. DTX1, DTX2, and PTX6 were not
      detected. MS-MS experiments revealed that the shellfish contained several other
      oxygenated metabolites of YTX in addition to 45-hydroxy yessotoxin (45OH-YTX).
      Gymnodimine (GYM) was present in the shellfish but not plankton and it was
      probably the residue from a previous GYM contamination event. Unlike the other
      toxins, GYM was concentrated in tissues outside the digestive gland and levels
      did not decrease over 5 months. The depuration rates of YTX and PTXs from mussels
      were modelled.

PMID- 12220719
TI  - Purification and cloning of a novel C-type lectin-like protein with platelet
      aggregation activity from Trimeresurus mucrosquamatus venom.
AB  - TMVA, a novel C-type lectin-like protein that induces platelet aggregation in a
      dose-dependent manner, was purified from the venom of Trimeresurus
      mucrosquamatus. It consists of two subunits, alpha (15536 Da) and beta (14873
      Da). The mature amino acid sequences of the alpha (135 amino acids) and beta
      subunits (123 amino acids) were deduced from cloned cDNAs. Both of the sequences
      show great similarity to C-type lectin-like venom proteins, including a
      carbohydrate recognition domain. The cysteine residues of TMVA are conserved at
      positions corresponding to those of flavocetin-A and convulxin, including the
      additional Cys135 in the alpha subunit and Cys3 in the beta subunit. SDS-PAGE,
      mass spectrometry analysis and amino acid sequence showed that native TMVA exists
      as two convertible multimers of (alpha beta)(2) and (alpha beta)(4) with
      molecular weights of 63680 and 128518 Da, respectively. The (alpha beta)(2)
      complex is stabilized by an interchain disulfide bridge between the two alpha
      beta-heterodimers, whereas the stabilization of the (alpha beta)(4) complex seems
      to involve non-covalent interactions between the (alpha beta)(2) complexes.

PMID- 12220720
TI  - Sympathetic nervous system activation, antivenin administration and
      cardiovascular manifestations of scorpion envenomation.
AB  - We performed two-dimensional echocardiograms and determined plasma norepinephrine
      levels on admission and at 24h after hospitalization, in 16 children with
      scorpion envenomation. All patients came from areas where scorpions have been
      identified as Tityus zulianus and received antivenin at the site of the accident
      or upon admission. Based on the presence or absence of cardiovascular
      manifestations, patients were divided into two groups. GROUP A: 10 patients had
      cardiovascular manifestations of pulmonary edema. Four patients had mild
      pulmonary edema (Left ventricular ejection fraction: 0.43+/-0.19) and six had
      moderate to severe pulmonary edema (Ejection fraction: 0.31+/-0.09. p=NS, M+/
      SD). Plasma norepinephrine was elevated on admission (1279+/-824) and decreased
      at 24h in seven of eight patients (474+/-140 pg/ml, p<0.03). GROUP B: Six
      patients had no cardiovascular manifestations. These patients had normal chest X
      rays and normal echocardiograms. Plasma norepinephrine was not elevated (188+/
      180 pg/ml). Time interval from the accident to antivenin administration was
      significantly longer in Group A compared to Group B (4.5+/-3.3 vs 1.2+/-0.4h,
      p<0.03) and correlated directly with the absolute change in plasma norepinephrine
      (r=0.76, p<001). Consequently, we strongly recommend very early administration of
      antivenin in the medical management of scorpion envenomation by T. zulianus.

PMID- 12220721
TI  - Multiple ciguatoxins present in Indian Ocean reef fish.
AB  - Optimised gradient reversed-phase high-performance liquid chromatography
      electrospray ionisation mass spectrometry (LC/MS) methods, in combination with a
      [3H]-brevetoxin binding assay (RLB), revealed multiple ciguatoxins in a partially
      purified extract of a highly toxic Lutjanus sebae (red emperor) from the Indian
      Ocean. Two major ciguatoxins of 1140.6 Da (I-CTX-1 and -2) and two minor
      ciguatoxins of 1156.6 Da (I-CTX-3 and -4) were identified. Accurate mass analysis
      revealed that I-CTX-1 and -2 and Caribbean C-CTX-1 had indistinguishable masses
      (1140.6316 Da, at 0.44 ppm resolution). Toxicity estimated from LC/MS/RLB
      responses indicated that I-CTX-1 and -2 were both approximately 60% the potency
      of Pacific ciguatoxin-1 (P-CTX-1). In contrast to ciguatoxins of the Pacific
      where the more oxidised ciguatoxins are more potent, I-CTX-3 and -4 were
      approximately 20% of P-CTX-1 potency. Interconversion in dilute acid or on
      storage, typical of spiroketal and hemiketal functionality found in P-CTXs and C
      CTXs, respectively, was not observed to occur between I-CTX-1 and -2. The ratio
      of CTX-1 and -2 varied depending on the fish extract being analysed. These
      results suggest that I-CTX-1 and -2 may arise from separate dinoflagellate
      precursors that may be oxidatively biotransformed to I-CTX-3 and -4 in fish.

PMID- 12220722
TI  - Role of the structurally disordered N- and C-terminal residues in the Janus-faced
      atracotoxins.
AB  - The Janus-faced atracotoxins (J-ACTXs) are a family of insect-specific excitatory
      toxins isolated from the venom of Australian funnel-web spiders (genera Atrax and
      Hadronyche). In addition to a classical cystine knot motif, these toxins contain
      a rare vicinal disulfide bond. While the vicinal disulfide is known to be
      critical for insecticidal activity, the role of other residues in toxin function
      remains to be determined. In this study, we probed the role of the structurally
      disordered N- and C-terminal residues using a panel of recombinant mutants of the
      prototypic family member J-ACTX-Hv1c. We found that the structurally disordered C
      terminal residues (Glu 36 and Pro 37) were dispensable for toxin function.
      However, whereas deletion of Ala 1 had minimal impact on toxin function, deletion
      of both Ala 1 and Ile 2 decreased insecticidal activity more than 70-fold. We
      propose that Ile 2 forms a part of the target binding site of J-ACTX-Hv1c.

PMID- 12220723
TI  - A novel phospholipase A(2) from the venom glands of Bungarus candidus: cloning
      and sequence-comparison.
AB  - The presence of phospholipase A(2) (PLA(2)) in the venom of Malayan krait
      (Bungarus candidus) and its structure were studied. The PLA(2) cDNAs from the
      venom gland of B. candidus (Indonesia origin) were amplified by the polymerase
      chain reactions (PCR) and cloned. The primers used were based on the cDNA
      sequences of several homologous B. multicinctus venom PLA(2)s. In addition to the
      A-chains of beta-bungarotoxins, a novel B. candidus PLA(2) was cloned and its
      full amino acid sequence deduced. Having totally 125 amino acid residues, the
      PLA(2) contains a pancreatic loop and is 61% identical to the acidic PLA(2) of
      king cobra venom. However, the enzyme was not detected from the venom sample. Its
      structural relationships to other elapid venom PLA(2)s were analyzed with a
      phylogenetic tree and discussed.

PMID- 12220724
TI  - Molecular cloning of HR1a and HR1b, high molecular hemorrhagic factors, from
      Trimeresurus flavoviridis venom.
AB  - HR1a and HR1b are two high molecular weight (P-III class) hemorrhagic factors in
      the venom of Trimeresurus flavoviridis. In this study, we cloned cDNAs of the
      HR1a and HR1b precursors and analyzed their nucleotide sequences. The cDNA for
      HR1a was 2368 nucleotides in length and encoded an open reading frame (ORF) of
      609 amino acids; that for HR1b was 2237 nucleotides and encoded an ORF of 614
      amino acids. Both cDNAs belonged to the N-III class consisting of signal, pro,
      metalloproteinase, disintegrin-like and cysteine-rich regions, and shared strong
      amino acid sequence similarity (74.4%). The HR1b precursor was found to have an
      additional seven amino acid sequence at the carboxyl terminus compared with a
      mature form of HR1b.

PMID- 12220726
TI  - Expression of mRNA for growth hormone-releasing hormone and splice variants of
      GHRH receptors in human malignant bone tumors.
AB  - Splice variants (SV) of receptors for growth hormone-releasing hormone (GHRH)
      have been found in several human cancer cell lines. GHRH antagonists inhibit
      growth of various human cancers, including osteosarcomas and Ewing's sarcoma,
      xenografted into nude mice or cultured in vitro and their antiproliferative
      action could be mediated, in part, through these SV of GHRH receptors. In this
      study, we found mRNA for the SV(1) isoform of GHRH receptors in human
      osteosarcoma line MNNG/HOS and SK-ES-1 Ewing's sarcoma line. We also detected
      mRNA for GHRH, which is apparently translated into the GHRH peptide and secreted
      by the cells, as shown by the presence of GHRH-like immunoreactivity in the
      conditioned media of cell cultures. In proliferation studies in vitro, the growth
      of SK-ES-1 and MNNG/HOS cells was dose-dependently inhibited by GHRH antagonist
      JV-1-38 and an antiserum against human GHRH. Our study indicates the presence of
      an autocrine stimulatory loop based on GHRH and SV(1) of GHRH receptors in human
      sarcomas. The direct antiproliferative effects of GHRH antagonists on malignant
      bone tumors appear to be exerted through the SV(1) of GHRH receptors on tumoral
      cells.

PMID- 12220727
TI  - Triple therapy with octreotide, galanin and serotonin induces necrosis and
      increases apoptosis of a rat colon carcinoma.
AB  - A rat colonic adenocarcinoma was implanted subcutaneously (s.c.) in nude mice.
      After 7 days, the animals were divided into different groups. Two groups received
      subcutaneous injections twice daily with 3 or 6 micro g/kg body weight
      octreotide, galanin and serotonin. Three groups were respectively treated with
      20, 30, and 40 micro g/kg body weight of the previously mentioned bioactive
      substances. Control group received only saline solution in the same fashion as
      treated animals. The treatment lasted for 5 days. The tumour volume and weight,
      the relative density of blood vessels, of tumour necrotic tissue, of apoptotic
      nuclei and of proliferating nuclei were measured. Apoptosis was detected by in
      situ labelling of nuclear DNA fragmentation according to TUNEL method, and
      proliferation by immunocytochemistry. Morphometry was done with the classical
      stereological point-counting method. Food consumption, animal weight, faeces
      weight and its water content were measured for 3 days before and after treatment.
      Triple therapy with 3 and 6 micro g/kg body weight had no effect on any of the
      parameters measured, except in reducing the relative volume density of tumour
      blood vessels. Treatment with 20, 30 and 40 micro g/kg body weight of the
      previously mentioned bioactive substances reduced the tumour volume, the relative
      volume density of blood vessels and increased the relative volume density of
      necrotic tissue and of apoptotic nuclei (in the 20 micro g group). However, there
      was no difference between treated mice and controls regarding the relative volume
      density of proliferating nuclei. There was no statistical difference between
      treated animals regarding food consumption, body weight, faeces weight and its
      water content before and during treatment. The present study confirms that triple
      therapy with octreotide, galanin and serotonin causes regression of a rat colon
      carcinoma. It further showed that optimum treatment dose is 20 micro g/kg body
      weight of each bioactive substance. Moreover, this therapy regime does not show
      apparent side effects in the experiments carried out on mice.

PMID- 12220728
TI  - Characterization of VIP and PACAP receptors in cultured rat penis corpus
      cavernosum smooth muscle cells and their interaction with guanylate cyclase-B
      receptors.
AB  - Penile corpus cavernosum smooth muscle relaxation can be induced by both cyclic
      AMP and cyclic GMP-elevating agents, but possible interactions between these two
      signalling pathways are still poorly understood. Using in vitro cultured rat
      penile corpus cavernosum smooth muscle (CCSM) cells, we have characterized the
      local expression and functional activities of receptors for the cAMP-elevating
      peptides, PACAP and VIP, and for the cGMP-elevating peptides, CNP and ANP.
      Stimulation of the cells with various concentrations of PACAP(-27/-38) or VIP
      resulted in rapid and dose-dependent increases in cyclic AMP levels. RT-PCR
      analyses revealed gene expression of PAC(1) and VPAC(2) but not of VPAC(1)
      receptors in the cells. The natriuretic peptide, CNP, and the nitric oxide donor,
      sodium nitroprusside, were capable of enhancing cyclic GMP formation, indicating
      the presence of membrane-associated in addition to soluble guanylate cyclase
      (sGC) activities in these cells. Findings that cyclic GMP formation was
      preferentially activated by CNP but not by the related peptide, ANP, were
      consistent with RT-PCR analyses, demonstrating gene expression of the CNP
      receptor, GC-B, but not of the ANP receptor, GC-A, in these cells. Prior exposure
      of the cells to 10(-8) M PACAP resulted in a marked down-regulation of GC-B
      activity, whereas sGC was not affected. These findings provide functional and
      molecular evidence for the presence of three receptors, PAC(1), VPAC(2) and GC-B,
      involved in cyclic nucleotide signalling in penile CCSM cells. The observed cross
      talk of the PACAP/VIP receptors with GC-B but not with sGC may have implications
      for the therapy of erectile dysfunction.

PMID- 12220729
TI  - Role of gastrin in the development of gastric mucosa, ECL cells and A-like cells
      in newborn and young rats.
AB  - Histamine-producing ECL cells and ghrelin-producing A-like cells are
      endocrine/paracrine cell populations in the acid-producing part of the rat
      stomach. While the A-like cells operate independently of gastrin, the ECL cells
      respond to gastrin with mobilization of histamine and chromogranin A (CGA)
      derived peptides, such as pancreastatin. Gastrin is often assumed to be the
      driving force behind the postnatal development of the gastric mucosa in general
      and the ECL cells in particular. We tested this assumption by examining the
      oxyntic mucosa (with ECL cells and A-like cells) in developing rats under the
      influence of YF476, a cholecystokinin-2 (CCK(2)) receptor antagonist. The drug
      was administered by weekly subcutaneous injections starting at birth. The body
      weight gain was not affected. Weaning occurred at days 15-22 in both YF476
      treated and age-matched control rats. Circulating gastrin was low at birth and
      reached adult levels 2 weeks after birth. During and after weaning (but not
      before), YF476 greatly raised the serum gastrin concentration (because of
      abolished acid feedback inhibition of gastrin release). The weight of the stomach
      was unaffected by YF476 during the first 2-3 weeks after birth. From 4 to 5 weeks
      of age, the weight and thickness of the gastric mucosa were lower in YF476
      treated rats than in controls. Pancreastatin-immunoreactive cells (i.e. all
      endocrine cells in the stomach) and ghrelin-immunoreactive cells (A-like cells)
      were few at birth and increased gradually in number until 6-8 weeks of age
      (control rats). At first, YF476 did not affect the development of the
      pancreastatin-immunoreactive cells, but a few weeks after weaning, the cells were
      fewer in the YF476 rats. The ECL-cell parameters (oxyntic mucosal histamine and
      pancreastatin concentrations, the histidine decarboxylase (HDC) activity, the HDC
      mRNA levels and serum pancreastatin concentration) increased slowly until weaning
      in both YF476-treated and control rats. From then on, there was a further
      increase in the ECL-cell parameters in control rats but not in YF476 rats. The
      postnatal development of the ghrelin cells (i.e. the A-like cells) and of the A
      like cell parameters (the oxyntic mucosal ghrelin concentration and the serum
      ghrelin concentrations) was not affected by YF476 at any point. We conclude that
      gastrin affects neither the oxyntic mucosa nor the endocrine cells before
      weaning. After weaning, CCK(2) receptor blockade is associated with a somewhat
      impaired development of the oxyntic mucosa and the ECL cells. While gastrin
      stimulation is of crucial importance for the onset of acid secretion during
      weaning and for the activation of ECL-cell histamine formation and secretion, the
      mucosal and ECL-cell growth at this stage is only partly gastrin-dependent. In
      contrast, the development of the A-like cells is independent of gastrin at all
      stages.

PMID- 12220730
TI  - Oxytocin decreases plasma levels of thyroid-stimulating hormone and thyroid
      hormones in rats.
AB  - Oxytocin (OXT) administered to rats induces several long-lasting physiological
      and metabolic effects. The aim of the present study was to investigate the
      effects of oxytocin treatment on plasma levels of thyroid-stimulating hormone
      (TSH), free thyroxine (fT4) and free triiodothyronine (fT3). For this purpose,
      oxytocin or NaCl was administered intracerebroventricularly (i.c.v.) (0.3 micro
      g) or subcutaneously (s.c.) (1 mg/kg) once a day for 5 days to male rats. Five or
      ten days after the last injection, rats were decapitated, blood was collected and
      hormone levels were analyzed by fluoroimmunoassay. The oxytocin treatment i.c.v.
      decreased plasma levels of TSH (p<0.05), fT3 (p<0.01) and fT4 (p<0.05) when
      measured at day 5 after oxytocin treatment, whereas the effect was abolished when
      measured at day 10. Oxytocin treatment s.c. did not affect plasma levels of TSH,
      fT3 or fT4. Thus, the effect seems to have been mediated within the central
      nervous system, and TSH and the thyroid hormones may be involved in some of the
      metabolic effects in response to oxytocin.

PMID- 12220731
TI  - Calcitonin gene-related peptide and adrenomedullin release in humans: effects of
      exercise and hypoxia.
AB  - Calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) are potent
      vasorelaxant peptides. This study examined exercise-induced changes in CGRP and
      AM levels in 12 healthy sea level natives at sea level (SL) and subsequently
      after 24 h (HA1) and 5 days (HA5) in high altitude hypoxia (4559 m). Plasma
      values of CGRP, AM, calcitonin, noradrenaline, adrenaline, lactate and heart rate
      were measured at rest and during maximal exercise (W(max)). On each study day,
      the dopamine D(2)-receptor antagonist, domperidone (30 mg; n=6), or no medication
      (n=6) was given 1 h before exercise. W(max) at SL, HA1 and HA5 increased CGRP and
      AM along with heart rate, lactate and catecholamines, whereas, calcitonin
      remained unchanged. The maximal CGRP levels at W(max) were significantly
      decreased at HA1 (74.3+/-6.1 pmol/l; p=0.002) and HA5 (69.6+/-6.0 pmol/l;
      p<0.001) compared to maximal CGRP at SL (85.1+/-4.9 pmol/l). A similar pattern
      was observed for lactate and the relation between CGRP and lactate release showed
      a close linear correlation (r(2)=0.63, P<0.0001). Domperidone produced a marked
      increase in noradrenaline at W(max), but had no affect on CGRP or AM. In
      conclusion, CGRP release during hypoxic exercise does not respond to domperidone
      induced changes in circulating levels of noradrenaline, rather the release may be
      directly related to the production of lactate.

PMID- 12220732
TI  - Somatostatin inhibits glucagon-like peptide-1-induced insulin secretion and
      proliferation of RINm5F insulinoma cells.
AB  - Glucagon-like peptide-1 [GLP-1; formerly GLP-1(7-36)amide] and somatostatin (SS)
      are two postprandially or paracrine released peptide hormones that regulate
      insulin secretion from pancreatic islets. Using the rat insulinoma cell line
      RINm5F as a model, we investigated the effects of both peptides alone and in
      combination on insulin release, proliferation, and intracellular signal
      transduction. In addition, we determined the SS receptor subtypes expressed and
      involved by reverse transcription-polymerase chain reaction and use of selective
      SS agonists. GLP-1 stimulated insulin release, cell proliferation, intracellular
      cAMP accumulation and activation of the transcription factor cAMP-response
      element binding protein (CREB) which all could be reduced to basal values by co
      incubation with SS. Incubation with SS alone did not affect basal levels. RINm5F
      cells express the somatostatin receptor (sst) subtypes sst1 and sst2 as well as
      traces of sst3. In accordance, the sst1- or sst2-selective non-peptide agonists L
      797591 or L-054522 and peptide agonist octreotide (SMS 201995; sst2, sst3, and
      sst5 selective) potently inhibited GLP-1-induced insulin secretion whereas the
      sst3-selective agonist L-796778 showed little effect. Moreover, the sst1- and
      sst2-selective agonists slightly reduced also basal insulin release. The
      experiments show that GLP-1 and SS are perfect opponents for regulating
      pancreatic beta-cell insulin secretion.

PMID- 12220733
TI  - Hypothalamic ventromedial and arcuate neurons of normal and postnatally
      overnourished rats differ in their responses to melanin-concentrating hormone.
AB  - Melanin-concentrating hormone (MCH) is a neuropeptide involved in regulation of
      food intake and body weight. The study aimed to detect possible differences in
      responses of hypothalamic ventromedial and arcuate neurons to MCH, depending on
      the short-term nutritional state (fed versus food-deprived) and on the long-term
      state in overweight rats due to early postnatal overnutrition. The effect of MCH
      on a single-unit activity was studied in brain slices of normal and overweight
      rats. The latter (n=16) were raised till weaning in small litters (SL) of 3 pups
      compared to 10 pups in control litters (CL) and gained significantly greater body
      mass. Whereas MCH in effective concentrations in the pico- to nanomolar range
      could increase or suppress the activity of ventromedial or arcuate neurons
      studied in male normal fed or food-deprived (24 h) rats, its action became shaped
      in an unidirectional way in overweight, hyperphagic rats. Medial arcuate neurons
      (n=25) from hyperphagic rats were predominantly activated by MCH (p<0.05, paired
      t-test). This effect differed significantly from that induced on neurons (n=27)
      of control rats. Ventromedial neurons (n=34) of overweight rats were
      predominantly inhibited. Activation of arcuate neurons may induce feeding in
      particular through release of neuropeptide Y (NPY). Inhibition of ventromedial
      neurons may contribute to reduced energy expenditure. The increased expression of
      one response type to MCH by a neuronal population in overweight, hyperphagic rats
      might reflect a general mechanism of neurochemical plasticity and also suggest a
      participation of the peptide in long-term regulation of food intake and body
      weight in this model of obesity.

PMID- 12220734
TI  - The primary structures and myotropic activities of two tachykinins isolated from
      the African clawed frog, Xenopus laevis.
AB  - Two peptides with limited structural similarity to mammalian substance P (SP) and
      neurokinin A (NKA) have been isolated from extracts of the intestine of the
      African clawed frog (Xenopus laevis). The primary structure of an SP-like peptide
      was established as: Lys-Pro-Arg-Pro-Asp-Gln-Phe-Tyr-Gly-Leu-Met.NH(2), which is
      identical to the previously characterized peptide, bufokinin isolated from the
      toad Bufo marinus. The primary structure of an NKA-related peptide was
      established as Thr-Leu-Thr-Thr-Gly-Lys-Asp-Phe-Val-Gly-Leu-Met.NH(2). Only the
      five amino acids at the C-terminal region of the peptide are identical to
      mammalian NKA whereas the N-terminal region shows no structural similarity to
      previously characterized tachykinins. Immunohistochemical investigations of the
      gut wall revealed a dense network of nerve fibres and nerve cell bodies
      containing SP/NKA-like substances. The myotropic effects of the Xenopus
      tachykinins were compared with the contractile effect of mammalian SP and NKA on
      isolated strips of circular smooth muscle from Xenopus stomach. No significant
      differences in potencies (-log EC(50)) or in intrinsic activities were observed
      between the Xenopus and mammalian peptides. The potencies for the Xenopus SP-like
      (8.49+/-0.15) and the NKA-like peptide (8.12+/-0.06) were similar suggesting that
      the amino acid sequence at the N-terminal region of the tachykinins is not
      important in activating the tachykinin receptors in Xenopus gastric smooth
      muscle. The maximum response to Xenopus SP (alpha=0.59+/-0.06) was significantly
      lower than to the NKA-like peptide (alpha=1.0) suggesting a more effective
      interaction of the NKA-like peptide with the tachykinin receptor(s) in Xenopus
      stomach.

PMID- 12220735
TI  - A polymorphism in the growth hormone-releasing hormone receptor gene: clinical
      significance?
AB  - Two forms of the growth hormone-releasing hormone (GHRH) receptor (GHRH-R) exist
      in terms of a polymorphism at codon 57. The most common allele possesses GCG,
      coding for Ala. This codon can also be ACG, replacing the Ala with Thr. The
      present study demonstrates that the latter occurs in about 20% of pituitary
      somatotrophinomas, removed from patients with acromegaly. Somatotrophinomas
      possessing the alternative allele respond, on average, more strongly to GHRH in
      terms of GH secretion in vitro than tumors which are homozygous for the more
      common allele. The distribution of the two allelic forms of the GHRH-R did not
      significantly differ between acromegalic and non-acromegalic subjects. Thus,
      while the alternative allelic forms may, at least partially, contribute to the
      variable response of serum GH levels to i.v. GHRH observed in acromegalic and
      normal subjects, it is unlikely that subjects possessing the rarer form
      containing Thr in place of Ala at residue 57 are at increased risk of developing
      acromegaly.

PMID- 12220736
TI  - Role of calcitonin gene-related peptide (CGRP) in chronic hypoxia-induced
      pulmonary hypertension in the mouse. Influence of gene transfer in vivo.
AB  - Calcitonin gene-related peptide (CGRP) is believed to play an important role in
      maintaining low pulmonary vascular resistance (PVR) and may be involved in
      modulating the pulmonary vascular response to chronic hypoxia. In the present
      study, an adenoviral vector encoding CGRP (AdRSVCGRP) was used to examine the
      effects of in vivo gene transfer of CGRP to the lung on increases in PVR, right
      ventricular mass, and pulmonary vascular remodeling that occurs in chronic
      hypoxia in the mouse. Following intratracheal administration of AdRSVCGRP or
      reporter gene mice were exposed to 16 days of chronic hypoxia (FIO(2) 0.10). The
      increase in pulmonary arterial pressure (PAP), PVR, right ventricular mass, and
      pulmonary vascular remodeling in response to chronic hypoxia was attenuated in
      animals overexpressing CGRP, whereas systemic arterial pressure was not altered.
      Following exposure to hypoxia, a subgroup of mice were treated with capsaicin,
      which did not significantly alter CGRP expression in the mouse lung. These data
      show that in vivo transfer of the CGRP gene to the lung attenuates the increase
      in PVR, right ventricular mass, and pulmonary vascular remodeling in chronically
      hypoxic mice with little effect on the systemic circulation. Moreover, these data
      suggest that adenoviral gene transfer of CGRP to the lung results in expression
      of the gene product in non-neural tissue.

PMID- 12220737
TI  - Neuron restrictive silencer factor as a modulator of neuropeptide gene
      expression.
AB  - We hypothesize that the transcription factor neuron restrictive silencer factor
      (NRSF) is an important determinant of the expression of the preprotachykinin
      (PPTA) gene (encoding substance P and Neurokinin A) and arginine vasopressin
      (AVP) both in neuronal and nonneuronal cells. NRSF, a zinc finger repressor
      protein, binds the NRSE motif found in many neuronal specific genes at a variety
      of promoter locations. However, it is found in a similar location at the major
      transcriptional start site, within both PPTA and AVP peptide promoters. We have
      correlated modulation of NRSF activity with expression of AVP and PPTA in a
      variety of cell types, indicating the general mechanism by which this protein may
      regulate expression. Specifically, they are as follows:(1). Expression of NRSF
      dramatically represses PPTA promoter activity in reporter gene constructs in
      primary cultures of DRG neurons.(2). The PPTA promoter activity is regulated
      differentially in osteoarthritic compared to normal chondrocytes. This regulation
      correlates with the region containing the NRSE site.(3). We have correlated a
      splice variant of NRSF with the establishment and progression of small cell lung
      carcinoma (SCLC) and demonstrated that NRSF variants can directly affect the
      activity of the AVP promoter in reporter gene constructs. If the deregulated
      expression of peptides in these diseases point to the mechanism determining the
      pathology, then perhaps targeting protocols that correct this deregulation may
      also reverse the specific disease phenotypes. Our data would indicate that
      modulation of NRSF activity would be a target for such intervention.

PMID- 12220738
TI  - Vasoactive intestinal peptide mRNA and immunoreactivity are decreased in fetal
      alcohol syndrome model.
AB  - Vasoactive intestinal peptide (VIP) regulates growth in the early post
      implantation embryo. Previous work has demonstrated that peptide agonists
      (SALLRSIPA and NAPVSIPQ) from downstream mediators that are regulated by VIP were
      able to prevent the alcohol-induced fetal death, growth restriction and
      microcephaly associated with fetal alcohol syndrome. Here we evaluated the role
      of VIP in this mouse model of fetal alcohol syndrome, to determine if fetal or
      maternal levels of VIP are altered. In addition, we evaluated whether peptide
      treatment would alter the effects of alcohol on VIP levels. Treatment groups
      included control, alcohol, and alcohol+peptides. VIP levels were measured with
      enzyme immunoassay [EIA] (Peninsula Laboratories, Belmont, CA). Quantitation of
      VIP expression was measured with rt-PCR using mimic cDNA primers. Embryo/decidual
      VIP levels were similar in control and alcohol-treated groups 6 h after
      treatment. However, in the embryo/deciduas at 12 and 24 h, VIP levels were below
      the EIA's detection limit in the alcohol-treated groups, and significantly lower
      than the control or peptide-pretreated groups (p<0.05). Maternal cortex VIP
      levels were undetectable and significantly lower in the alcohol-treated group
      than control or peptide+alcohol group at 6 and 12 h (p<0.001). VIP mRNA
      expression was quantitated in the embryo and deciduas, with a significant decline
      noted at 6 h to 58% of control levels (p=0.02). Pretreatment with the peptides
      attenuated the alcohol-induced decrease in VIP mRNA. These studies demonstrate
      that treatment with alcohol can decrease the expression and immunoreactivity of
      VIP in both maternal and fetal tissues. This alcohol-induced loss of a recognized
      regulator of embryonic growth and differentiation may contribute to the sequelae
      of toxicity observed in fetal alcohol syndrome.

PMID- 12220739
TI  - Behavioral perinatology: biobehavioral processes in human fetal development.
AB  - Behavioral perinatology is as an interdisciplinary area of research that involves
      conceptualization of theoretical models and conduct of empirical studies of the
      dynamic time-, place-, and context-dependent interplay between biological and
      behavioral processes in fetal, neonatal, and infant life using an epigenetic
      framework of development. The biobehavioral processes of particular interest to
      our research group relate to the effects of maternal pre- and perinatal stress
      and maternal-placental-fetal stress physiology. We propose that behavioral
      perinatology research may have important implications for a better understanding
      of the processes that underlie or contribute to the risk of three sets of
      outcomes: prematurity, adverse neurodevelopment, and chronic degenerative
      diseases in adulthood. Based on our understanding of the ontogeny of human fetal
      development and the physiology of pregnancy and fetal development, we have
      articulated a neurobiological model of pre- and perinatal stress. Our model
      proposes that chronic maternal stress may exert a significant influence on fetal
      developmental outcomes. Maternal stress may act via one or more of three major
      physiological pathways: neuroendocrine, immune/inflammatory, and vascular. We
      further suggest that placental corticotropin-releasing hormone (CRH) may play a
      central role in coordinating the effects of endocrine, immune/inflammatory, and
      vascular processes on fetal developmental outcomes. Finally, we hypothesize that
      the effects of maternal stress are modulated by the nature, duration, and timing
      of occurrence of stress during gestation. In this paper, we elaborate on the
      conceptual and empirical basis for this model, highlight some relevant issues and
      questions, and make recommendations for future research in this area.

PMID- 12220740
TI  - Hormone trajectories leading to human birth.
AB  - The mechanisms regulating human parturition and labor remain unknown. This
      ignorance is expensive as preterm birth is responsible for 70% of neonatal
      mortality and 50% of cerebral palsy. Methods for the prediction of preterm birth
      and treatments for women in preterm labor have poor efficacy reflecting our
      limited knowledge of the mechanisms involved. Recent research has supported the
      view that parturition is a cascade of events that commences early in pregnancy
      and involves the mother, fetus, placenta, membranes, cervix and myometrium.
      Although a number of the key hormones and proteins involved have been identified,
      the relationships between these factors in time and tissues remain unclear.
      Placental production of Corticotropin-releasing hormone (CRH) is proposed as an
      early event regulating the cascade of events. Central to the onset of parturition
      will be a mechanism for progesterone withdrawal and estrogen activation in human.
      Two forms of progesterone receptor with opposing actions exist in the human
      myometrium. Progesterone receptor A (PR-A) is a dominant negative repressor of
      progesterone receptor B (PR-B). Preliminary studies strongly support the
      hypothesis that the onset of human parturition is initiated by rising
      concentrations of PR-A in the myometrium.

PMID- 12220741
TI  - Molecular pharmacology and structure of VPAC Receptors for VIP and PACAP.
AB  - VIP and PACAP are two prominent neuropeptides which share two common G protein
      coupled receptors VPAC1 and VPAC2 while PACAP has an additional specific receptor
      PAC1. This paper reviews the present knowledge regarding three aspects of VPAC
      receptors including: (i). receptor specificity towards natural VIP-related
      peptides and pharmacology of synthetic agonists or antagonists; (ii). receptor
      signaling; (iii). molecular basis of ligand-receptor interaction as determined by
      site-directed mutagenesis, construction of receptor chimeras and structural
      modeling.

PMID- 12220742
TI  - The increased proliferation of cultured neuroblastoma cells treated with
      vasoactive intestinal peptide is enhanced by simultaneous inhibition of neutral
      endopeptidase.
AB  - Vasoactive intestinal peptide (VIP) stimulates the neuroblastoma cell line (NMB)
      to proliferate. Neuropeptide activity can be inhibited by neutral endopeptidases
      that function intracellularly and in the extracellular milieu. NMB cells express
      neutral endopeptidase (NEP) activity that can be specifically inhibited by
      phosphoramidon (PA). Our data now show that phosphoramidon treatment increases
      the efficacy of VIP-stimulated neuroblastoma proliferation. These results suggest
      that membrane endopeptidases modulate VIP-associated cell proliferation and
      enhancement of endopeptidase activity may serve as a target for cancer therapy.

PMID- 12220743
TI  - Disregulation of proopiomelanocortin and contagious maladaptive behavior.
AB  - Self-injurious behavior (SIB) is an untreatable and often life-threatening
      problem among individuals with developmental disorders, especially those
      diagnosed with autism. Functioning, relationships and processing of the
      proopiomelanocortin (POMC) system are "uncoupled" in subgroups of self-injuring
      individuals resulting in different ratios of ACTH and opioids in the bloodstream,
      particularly under conditions of stress. In this study, relations between SIB and
      POMC were evaluated in a multi-year study of the largest prospective sample
      studied to date. Observations were collected on palmtop computers for 45
      treatment-resistant patients who exhibited chronic SIB. Behavior of each subject
      was observed in natural settings without disruption or intrusion, for continuous,
      2.5-h periods, two times a day (morning and afternoon), 4 days a week for two
      consecutive weeks, for a total of 40 h/subject. Blood was collected in the
      morning, late afternoon and immediately after an SIB episode on two separate
      occasions separated by at least 6 months. Levels of beta-endorphin (beta E) and
      ACTH were assayed by RIA. We discovered that the SIB was the best predictor of
      subsequent SIB. Moreover, the majority of subjects exhibited this contagious
      pattern of SIB. Levels of POMC fragments were reliable over a 6- to 9-month
      period. Subjects exhibiting POMC disregulation characterized by high morning
      levels of beta E had the highest transitional probabilities of SIB (i.e.
      contagious patterns; F=8.17, P<0.01). These findings suggest that subjects with
      "contagious" SIB may represent a behavioral phenotype associated with
      disregulated expression of the POMC gene.

PMID- 12220744
TI  - Hearing voices: patient-centered care with diverse populations.

PMID- 12220745
TI  - Doctor-parent-child relationships: a 'pas de trois'.
AB  - Adult participants play a pivotal role in doctor-parent-child interactions at the
      general practitioner's (GP's) surgery. The child's opportunities to participate
      are rather limited and parental speaking for the child is, in a way,
      institutionally co-constructed. This study aimed at further characterizing the
      relationships within this triad by developing a typology of doctor-parent-child
      interactions, which classified adult behavior in terms of supporting versus non
      supporting child participation. The child's participation was described in terms
      of display of involvement and turning for support. Analyses of 105 videos show
      that in most consultations, both GP and parent displayed non-supportive behavior.
      Despite the GPs' initial efforts to involve the child in the interaction, 90% of
      the consultations ended up in a non-participatory way. During this last segment
      of diagnosis and treatment information, the child's voice was hardly heard, as
      reflected in the minimal involvement displayed and the absence of turning to the
      parent for support. It is concluded that the bi-directional perspective chosen in
      this analysis allowed for a better understanding of the underlying mechanisms
      leading to the stereotypical picture in both literature and actual practice of
      triadic medical interactions being dominated by both adult participants. The low
      degree of child participation should not solely be seen as a consequence of adult
      behavior, but rather as a co-construction of all three participants. The results
      are discussed from a pedagogical perspective, and implications for medical
      practice are formulated.

PMID- 12220746
TI  - Patients' experience of cancer: evidence of the role of 'fighting' in collusive
      clinical communication.
AB  - Clinical communication with patients with cancer should be based on an accurate
      understanding of psychological responses to cancer, but existing assumptions
      about these responses may not be accurate. Male and female ambulant patients (N =
      30) provided a sample that varied in type, stage and prognosis of cancer.
      Interviews about their experience of cancer were audio-recorded and analysed
      qualitatively. The predominant response was a desire to conceal emotional
      distress, often to protect others including family and clinicians. Patients
      perceived clinicians as promoting 'fighting' and a 'positive attitude'. However,
      for patients, these responses meant resisting the expression of emotional
      distress rather than the disease. By encouragement to 'fight' and 'be positive',
      clinicians may therefore collude with patients' emotional suppression. For some
      patients, cancer led to re-evaluation of life; future research should examine
      whether and how clinical communication influences this form of adjustment.

PMID- 12220747
TI  - Evaluation of a patient-centred approach in generalized musculoskeletal chronic
      pain/fibromyalgia patients in primary care.
AB  - The aim of this paper is to assess whether patient-centred consultations are more
      effective than the usual style of consultations used by general practitioners
      with patients suffering from benign chronic musculoskeletal pain and
      fibromyalgia. It also seeks to evaluate the differential characteristics of these
      two clinical groups of symptoms. The study was designed as a cluster randomised
      and simple blind trial. Twenty general practitioners took part and 110 patients
      were recruited. Compared with patients who received the usual treatment from
      their family physician, those who received a patient-centred approach showed
      greater improvement after 1 year in terms of psychological distress (anxiety) and
      number of tender points, as well as showing positive trends in some important
      outcomes such as pain intensity. Significantly better results were observed in
      those patients suffering chronic pain than in those with fibromyalgia,
      particularly as regards associated symptoms, self-rated pain and physical
      mobility as measured by the Nottingham health profile.

PMID- 12220748
TI  - Emotional profile of physicians who interview frequent attenders.
AB  - Seventy-five physicians at primary health care centers in Spain described their
      emotions and thoughts during interviews with frequent attenders. Emotion scales
      were developed by factor and reliability analysis. Positive emotions were
      associated with younger physician age and with the thought "This patient really
      needs me." Feelings of lack of control were associated with rural centers and
      with the thoughts "Oh my God, him/her again!" and "This patient is really a
      pain." Anxiogenic emotions were associated with greater workload, requests for
      tests, requests to see the doctor outside regular hours, and the thoughts "Oh my
      God, him/her again!" and "I think this patient is trying to use me." Guilt
      feelings were associated with a lower perceived ability to solve the patient's
      problem, and with a poor physician-patients relationship. Sadness was associated
      with more frequent referrals to specialists. Awareness and acceptance of their
      emotions may improve physicians' emotional intelligence and physician-patient
      relationships.

PMID- 12220749
TI  - Working with suffering.
AB  - The past century has shown that human beings are capable of genocidal destruction
      of millions of other humans based on ethnicity or race. Clinicians today are
      likely to encounter patients who are survivors of inflicted atrocities and abuse.
      People fleeing horrendous circumstances bring persisting memories that produce
      symptoms even for the next generation. Families carry the knowledge-personal,
      cultural, familial, and sometimes individual-of the depths of destruction that
      human beings can do to one another. Suffering derives from the memory, both
      physical and mental, of what other persons inflicted; it has multiple dimensions
      that patients may not express explicitly; instead they may frame their experience
      of suffering in terms of pain. Diagnostic labels such as post-traumatic stress
      disorder or somatization are inadequate to convey human comprehension of
      suffering. Clinicians around the world need to be willing and able to acknowledge
      and witness the profound sources of experiential pain in the lives of their
      patients.

PMID- 12220750
TI  - Patient-centred consultations and outcomes in primary care: a review of the
      literature.
AB  - Although 'patient-centred' consulting skills are increasingly seen as crucial for
      the delivery of effective primary care, there is significant lack of clarity over
      the precise definition of the term, optimal methods of measurement, and the
      relationship between patient-centred care and patient outcomes. The present study
      sought to review all empirical studies to date that have investigated the
      relationship between measures of patient-centred consulting and outcomes in
      primary care, and to examine the methodological rigour of the studies. A number
      of observational studies were identified, all of which reported some
      relationships between doctor behaviour defined as 'patient-centred' and a variety
      of patient health outcomes. However, the pattern of associations was not clear or
      consistent, and some of the studies had shortcomings in terms of their internal
      and external validity. Although the current evidence base may be suggestive of a
      relationship between patient-centred consulting behaviour and patient outcomes,
      the case has not been made definitively.

PMID- 12220751
TI  - Breaking bad news: structured training for family medicine residents.
AB  - Previous research has shown that physicians experience incompetence and
      difficulty in dealing with patients' feelings after they have broken bad news to
      them. During the past 10 years, we have implemented a longitudinal training
      program targeting these issues. The present article describes this training and
      discusses its contribution to doctors' skills at approaching distressed patients.
      In order to cope with breaking bad news to patients and their families,
      physicians should be skilled at crisis intervention and communication techniques.
      They should also be aware of their personal attitudes and emotional reactions
      when breaking bad news. Each session encompassed these areas, as well as the most
      prominent issues arising when breaking bad news. In a 1-5 Likert scale, the
      course received an overall score of 4.47 (S.D. 0.51). Participants noted that
      they had gained relevant communication skills for future patient encounters.

PMID- 12220752
TI  - Liking in the physician--patient relationship.
AB  - Patients and physicians in established relationships (261 patients and their 44
      physicians) were asked after a medical visit how much they liked each other and
      how much they felt liked, along with questions concerning patient health,
      physician and patient satisfaction, and the patient's affective state. Patients
      were re-contacted 1 year later and asked about their satisfaction with the same
      physician and whether they had considered changing physicians during the year.
      Patients' and physicians' ratings indicated mutuality of liking, as well as
      accuracy of estimating the other's liking for the self. The physician's liking
      for the patient was positively associated with the following variables: better
      patient health, more positive patient affective state after the visit, more
      favorable patient ratings of the physician's behavior, greater patient
      satisfaction with the visit, and greater physician satisfaction with the visit.
      The patient's liking for the physician was positively associated with better self
      reported health, a more positive affective state after the visit, more favorable
      ratings of the physician's behavior, and greater visit satisfaction. Both the
      physician's liking for the patient and the patient's liking for the physician
      positively predicted the patient's satisfaction 1 year later and were associated
      with a lower likelihood that the patient considered changing physicians during
      the year. Female physicians reported liking their patients more than male
      physicians did, and patients' ratings of how much they felt liked corroborated
      this difference. Patients also reported liking female physicians more than male
      physicians. A number of these results remained significant even after controlling
      for the patient's overall satisfaction with the medical visit.

PMID- 12220753
TI  - Referrals for bereavement counselling in primary care: a qualitative study.
AB  - The growth in the provision of counselling services in British primary care
      offers an opportunity for general practitioners (GPs) to refer patients to
      counsellors following bereavement. This study explores the factors that influence
      GPs referral decisions. Qualitative interviews were conducted with 50 GPs from
      two cities in southern UK. The study found that GPs draw on notions of abnormal
      bereavement in making referral decisions. Indicators of bereavement problems
      related to: the nature of the death; level of social support; and reaction to the
      death. GPs views about the types of patients likely to benefit from counselling
      were further criteria employed in referral decisions. The study indicated that
      consideration of these factors may discriminate against certain types of patients
      being referred. Further education in the range of psychological theories of
      bereavement may assist GPs in understanding their bereaved patients' experiences
      and in developing their skills in recognising abnormal reactions and making
      appropriate referrals.

PMID- 12220754
TI  - The multi-dimensional measure of informed choice: a validation study.
AB  - The aim of this prospective study is to assess the reliability and validity of a
      multi-dimensional measure of informed choice (MMIC). Participants were 225
      pregnant women in two general hospitals in the UK, women receiving low-risk
      results following serum screening for Down syndrome. The MMIC was administered
      before testing and the Ottawa Decisional Conflict Scale was administered 6 weeks
      later. The component scales of the MMIC, knowledge and attitude, were internally
      consistent (alpha values of 0.68 and 0.78, respectively). Those who made a choice
      categorised as informed using the MMIC rated their decision 6 weeks later as
      being more informed, better supported and of higher quality than women whose
      choice was categorised as uninformed. This provides evidence of predictive
      validity, whilst the lack of association between the MMIC and anxiety shows
      construct (discriminant) validity. Thus, the MMIC has been shown to be
      psychometrically robust in pregnant women offered the choice to undergo prenatal
      screening for Down syndrome and receiving a low-risk result. Replication of this
      finding in other groups, facing other decisions, with other outcomes, should be
      assessed in future research.

PMID- 12220755
TI  - Show me the evidence.

PMID- 12220756
TI  - Rh-disease. a perinatal success story.

PMID- 12220757
TI  - Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of
      treatment.
AB  - OBJECTIVE: To compare the efficacy of low-dose aspirin alone versus low-dose
      aspirin plus low molecular weight heparin in pregnant women with antiphospholipid
      syndrome and recurrent miscarriage as prophylaxis against pregnancy loss.
      METHODS: From a regional miscarriage clinic, 119 consecutive women with
      persistently positive tests for lupus anticoagulant and/or anticardiolipin
      immunoglobulin G and M antibody were invited to participate in a randomized,
      controlled trial between 1997 and 2000. After ethical approval and adherence to a
      written protocol, 12 women were unwilling to participate, five failed
      exclusion/inclusion criteria, and four were nonpregnant. Laboratory analysis was
      performed by Sheffield University Coagulation Department, electronically
      generated randomization by Manchester University Centre for Cancer Epidemiology,
      and data collection and analysis by a research officer at Leeds University.
      Viability ultrasound every 2 weeks was provided until 12 weeks' gestation before
      transfer to the pregnancy support antenatal clinic. RESULTS: Ninety-eight women
      were randomized before 12 weeks' gestation. Forty-seven received low-dose aspirin
      75 mg daily (group A), and 51 received low-dose aspirin plus low molecular weight
      heparin 5000 U subcutaneously daily (group B) throughout pregnancy. There were 13
      pregnancy losses and 34 live births in group A and 11 losses and 40 live births
      in group B. The live-birth rate was 72% in group A and 78% in group B (odds ratio
      1.39, 95% confidence interval 0.55, 3.47). There were no cases of maternal
      thrombosis in either group. CONCLUSION: A high success rate is achieved when low
      dose aspirin is used for antiphospholipid syndrome in pregnancy. The addition of
      low molecular weight heparin does not significantly improve pregnancy outcome.

PMID- 12220758
TI  - Neonatal outcome in pregnancies from ovarian stimulation.
AB  - OBJECTIVE: To study the neonatal outcome in pregnancies after ovarian
      stimulation, not including in vitro fertilization. The outcomes studied were
      multiple birth, preterm birth, and low birth weight among singletons, congenital
      malformations, and infant death. METHODS: We identified 4029 women who delivered
      between 1995-1999 after ovarian stimulation alone and compared them with 438,582
      women who neither had ovarian stimulation nor in vitro fertilization. We
      controlled for the confounding effect of year of birth, maternal age, parity, and
      length of subfertility before the pregnancy. RESULTS: The twinning rate was 5.9%
      in the study group and 1.2% in the control group. The triplet rate was 0.5% in
      the study group and 0.02% in the control group. A nearly doubling of the rate of
      monozygotic twinning was indicated in the study group compared with the control
      group. There was an excess of singleton preterm births and low birth weight
      infants in the study group, but this was mainly explainable by confounding of
      maternal age, parity, and subfertility. The rates of congenital malformations and
      perinatal deaths were increased, also mainly explainable by maternal
      characteristics. No increase in specific types of congenital malformations was
      seen. CONCLUSION: As the deviations in neonatal outcome after ovarian stimulation
      alone were reduced or disappeared when the confounding of maternal age, parity,
      and subfertility was taken into consideration, there is probably little direct
      effect of the stimulation procedure as such.

PMID- 12220759
TI  - Human immunodeficiency virus counseling and testing practices among North
      Carolina providers.
AB  - OBJECTIVE: To estimate the percentage of prenatal care providers who offer human
      immunodeficiency virus (HIV) testing to pregnant women, investigate how strongly
      testing is encouraged, and explore testing barriers. METHODS: Between January
      2001 and March 2001, we sent surveys to 1381 prenatal care providers in North
      Carolina, comprised of obstetricians, family physicians who practice obstetrics,
      and nurse-midwives. A total of 653 questionnaires were returned. RESULTS:
      Overall, 95.5% of providers who responded reported recommending HIV testing to
      all pregnant patients. Only 69.2% strongly recommend testing, with obstetricians
      (73.4%) and family physicians (70.1%) doing so at higher rates than nurse
      midwives (55.9%). Almost all respondents (96.9%) strongly recommend testing for
      women they perceive to be high risk, whereas 39.7% strongly recommend testing to
      women who have had an HIV test in the past 6 months. When women refuse testing,
      48.1% of practitioners inquire about the reason, and 28.2% reoffer the test at a
      future prenatal appointment. The most significant testing barriers were treating
      an HIV-positive woman (18.4%) and informing a patient she is HIV positive
      (14.8%). Respondents report that low literacy and culturally appropriate patient
      education materials would be most helpful to them. CONCLUSION: Among respondents,
      most prenatal care providers report that they recommend HIV testing to all
      pregnant women. However, many respondents base their decision about how strongly
      to recommend HIV testing on an assessment of the woman's risk for HIV exposure.
      Significant barriers to offering HIV testing were associated with managing an HIV
      positive patient. Providers were most in need of patient education materials.

PMID- 12220760
TI  - Outcome of pregnancies with vertical transmission of primary cytomegalovirus
      infection.
AB  - OBJECTIVE: To study the outcome of 50 pregnancies with documented vertical
      transmission of cytomegalovirus infection. METHODS: We recruited 50 pregnant
      women (51 fetuses) with primary cytomegalovirus infection and confirmed in utero
      transmission. Prenatal evaluation included diagnostic amniocentesis and repeated
      ultrasound examinations. Fetal diagnosis was made after 21 weeks' gestation by
      amniocentesis and based on virus isolation by culture, shell vial, and polymerase
      chain reaction (PCR). Cytomegalovirus infection in neonates was determined by
      urinary viral isolation after birth or histologic examination of tissue from
      aborted fetuses. Cerebral ultrasound, hearing assessment, and psychomotor
      development were investigated for all 18 live-born neonates. RESULTS: Thirty
      three of the 50 women (66%) elected termination of pregnancy. Ultrasonographic
      abnormalities associated with in utero fetal infection were observed in 11
      (21.5%) fetuses. Two of them continued to term; both were congenitally infected,
      and one had neurologic abnormalities. The positive predictive values of the PCR
      and virus isolation assessments performed in all 50 pregnancies (51 gestational
      sacs) were 92% and 93.7%, respectively. Seventeen pregnancies (18 fetuses)
      continued to term: four fetuses had neurologic abnormalities, of which three had
      normal prenatal ultrasound findings. The remaining 14 had normal neonatal
      assessments. CONCLUSION: Positive isolation of cytomegalovirus accompanied by
      positive PCR values in amniotic fluid provided approximately 94% certainty of in
      utero cytomegalovirus infection. The risk of postnatal neurologic abnormalities
      was 19% (three of 16) when there were no prenatal ultrasonographic abnormalities.

PMID- 12220761
TI  - Premenstrual daily fluoxetine for premenstrual dysphoric disorder: a placebo
      controlled, clinical trial using computerized diaries.
AB  - OBJECTIVE: To evaluate premenstrual daily dosing with fluoxetine for treatment of
      premenstrual dysphoric disorder. METHODS: After a two-cycle screening and one
      cycle single-blind placebo period, 260 women were randomized to fluoxetine 10 mg,
      fluoxetine 20 mg, or placebo (dosed daily from 14 days before next expected
      menses through the first full day of bleeding) for three cycles. Women recorded
      premenstrual dysphoric disorder symptoms daily using a computerized version of
      the Daily Record of Severity of Problems. RESULTS: Premenstrual daily fluoxetine
      20 mg demonstrated significant improvement in mean Daily Record of Severity of
      Problems luteal scores compared with placebo (P =.005); premenstrual daily
      fluoxetine 10 mg did not (P =.100). Daily Record of Severity of Problems total
      scores were statistically significantly improved by the first treatment cycle for
      both active treatment groups. However, only fluoxetine 20 mg remained
      statistically significantly superior to placebo throughout the active treatment
      phase of the trial. Both fluoxetine groups showed significant treatment advantage
      over placebo for mood-related symptoms (P <.05). Only premenstrual daily
      fluoxetine 20 mg showed significant treatment advantage over placebo for physical
      symptoms of breast tenderness (P <.001), bloating (P =.001), and joint/muscle
      pain (P =.037). Treatment was well tolerated; discontinuations due to adverse
      events did not differ among the three groups (P =.316). CONCLUSION: Premenstrual
      daily dosing with fluoxetine effectively treats mood, physical, and social
      functioning symptoms associated with premenstrual dysphoric disorder. Fluoxetine
      20 mg appears to have comparable tolerability with, and better efficacy than,
      fluoxetine 10 mg.

PMID- 12220762
TI  - Significant increase of benign endometrial cells on Papanicolaou smears in women
      using hormone replacement therapy.
AB  - OBJECTIVE: To determine the prevalence of benign endometrial cells on
      Papanicolaou smears from postmenopausal women and to compare the prevalence and
      histologic diagnosis in women who use hormone replacement therapy (HRT) with
      those who do not. METHODS: Papanicolaou smear diagnoses from postmenopausal women
      and women over age 50 between April 1995 and December 1998 were retrieved and
      linked with follow-up smears and biopsies. Hormone status of women with benign
      endometrial cells smears was obtained from requisition forms or phone
      conversation with primary care providers. All surgical pathology material as well
      as Papanicolaou smears from women subsequently diagnosed with endometrial
      adenocarcinoma were reviewed. Relative prevalence with 95% confidence intervals
      was determined. RESULTS: A total of 589 of 52,662 Papanicolaou smears from
      postmenopausal women were diagnosed with benign endometrial cells, a prevalence
      of 1.1%. Also, HRT was reported in 16,073 (31%), no HRT was reported in 33,170
      (63%), and hormone status was unknown in 3379 (6%). Smears from 245 HRT users,
      324 nonusers, and 20 with unknown hormone status were diagnosed with benign
      endometrial cells. There was a significant increased prevalence of benign
      endometrial cells in women on HRT compared with nonusers (relative prevalence
      1.56, 95% confidence interval 1.32, 1.84, P <.001). Among 436 women with known
      hormonal status and follow-up, 12 (2.7%) had endometrial carcinoma, three (1.5%)
      in HRT users and nine (3.7%) in nonusers (P =.175). In addition, HRT users had
      significantly less abnormal endometrial histology than non-HRT users (2.6% versus
      7.4%, P =.025). CONCLUSION: We found that HRT is significantly associated with an
      increased prevalence of benign endometrial cells on Papanicolaou smears. Women on
      HRT who have benign endometrial cells on their Papanicolaou smears, however, have
      less abnormal endometrial histology compared with women not using HRT who have
      benign endometrial cells on their Papanicolaou smears.

PMID- 12220763
TI  - Preference and compliance in postoperative thromboembolism prophylaxis among
      gynecologic oncology patients.
AB  - OBJECTIVE: To compare low molecular weight heparin and external pneumatic
      compression in terms of patient preference and compliance to determine if either
      of these two methods is superior in postoperative thromboembolism prophylaxis of
      gynecologic oncology patients. METHODS: A total of 211 patients undergoing major
      surgery for a suspected gynecologic malignancy were randomized to receive
      thromboembolism prophylaxis with either external pneumatic compression or low
      molecular weight heparin. Surveys regarding thromboembolism prophylaxis were
      completed by patients before surgery and approximately 7 days postoperatively.
      Patient preferences as well as reasons for patient dissatisfaction with
      prophylactic methods were elicited in the questionnaires. In addition, patient
      compliance with prophylaxis was recorded twice a day during hospitalization.
      Patients were not considered to be compliant with prophylaxis if the external
      pneumatic compression device was not functioning properly or if the
      administration of low molecular weight heparin was not given in a timely manner.
      RESULTS: The majority of patients were satisfied with the prophylactic method
      that they received to the extent that they would prefer the treatment they
      received to one they had not necessarily experienced. The postoperative
      preferences of 78% of patients receiving low molecular weight heparin and 74% of
      those wearing external pneumatic compression corresponded to what the patients
      actually received as a method of thromboembolism prevention. Patient compliance
      with prophylaxis was noted to be inadequate in ten of 104 (9.6%) patients
      receiving external pneumatic compression and seven of 103 (6.8%) patients
      receiving low molecular weight heparin. CONCLUSION: Pneumatic compression and low
      molecular weight heparin are similar both in terms of patient preference and
      compliance among gynecologic oncology patients receiving postoperative
      thromboembolism prophylaxis.

PMID- 12220764
TI  - Lower genital tract infection and endometritis: insight into subclinical pelvic
      inflammatory disease.
AB  - OBJECTIVE: To investigate the association between lower genital tract infections
      and subclinical PID. Fallopian tube damage is a common complication of acute
      symptomatic pelvic inflammatory disease (PID), yet most women with tubal factor
      infertility do not have a history of acute PID. Subclinical PID is believed to be
      an important cause of tubal factor infertility. METHODS: We conducted a cross
      sectional study among women attending a sexually transmitted diseases or
      ambulatory gynecology clinic. A convenience sample of 556 women with bacterial
      vaginosis, gonorrhea, or chlamydia, or women at risk for gonorrhea or chlamydia
      were enrolled. Women diagnosed with acute PID were not eligible to participate.
      The main outcome was subclinical PID, as defined by the presence of histologic
      endometritis. RESULTS: Subclinical PID was more common in women with lower
      genital tract infection than in uninfected women. Subclinical PID was present in
      27% of women with Chlamydia trachomatis (odds ratio 3.4; 95% confidence interval
      [CI] 1.8, 6.3) and in 26% of women infected with Neisseria gonorrhoeae (odds
      ratio 2.4; 95% CI 1.1, 5.1). Among women with bacterial vaginosis, 15% had
      endometritis (odds ratio 2.7; 95% CI 1.02, 7.2). CONCLUSION: Subclinical PID is
      common among women with lower genital tract infections. Additional prospective
      studies are necessary to determine the reproductive impact of these asymptomatic
      upper genital tract infections.

PMID- 12220765
TI  - Teratogenicity of recently introduced medications in human pregnancy.
AB  - OBJECTIVE: To determine how long it takes after a new drug is marketed to
      establish whether or not its use by pregnant women is likely to pose a
      substantial teratogenic risk. METHODS: We used standard clinical teratology
      resources to assess the teratogenic risks in human pregnancy of therapeutic
      treatment with 468 drugs approved by the US Food and Drug Administration between
      1980 and 2000. The teratogenic risk of each treatment was classified using the
      current online version of TERIS into one of three categories: 1) no risk, minimal
      risk, or unlikely to produce an increased risk; 2) associated with a small,
      moderate, or high risk; or 3) risk undetermined. RESULTS: We found that the
      teratogenic risk in human pregnancy was still undetermined for 91.2% of drug
      treatments approved in the United States between 1980 and 2000. The proportion of
      treatments classified as having an "undetermined" teratogenic risk was more than
      80% for drugs approved for marketing 0-4, 5-9, 10-14, or 15-20 years ago, but the
      highest proportion of drugs with an "undetermined" teratogenic risk was found
      among those approved 15-20 years ago. The agreement between TERIS risk ratings
      and Food and Drug Administration Use-in-Pregnancy Categories for 163 drugs that
      had been assessed by both systems was poor (kappa +/- standard error = 0.082 +/-
      0.042). CONCLUSION: We conclude that inadequate information is available for
      pregnant women and their physicians to determine whether the benefits exceed the
      teratogenic risks for most drug treatments introduced in the past 20 years.

PMID- 12220766
TI  - Fetal and neonatal mortality among twin gestations in the United States: the role
      of intrapair birth weight discordance.
AB  - OBJECTIVE: To examine the association of intrapair birth weight discordance with
      fetal and neonatal mortality. METHODS: We used the United States (1995-1997)
      Matched Multiple Birth File (n = 297,155). RESULTS: Among twin live births and
      stillborn fetuses, 29.9% had less than 5% birth weight discordance, 24.2% had 5
      9%, 29.6% had 10-19%, 11.1% had 20-29%, 3.4% had 30-39%, and 1.8% had 40% or
      more. The stillborn fetus rate increased progressively with increasing birth
      weight discordance for smaller and larger twins of the same sex. Compared with
      the less than 5% birth weight discordance category, the adjusted odds ratios (OR)
      (95% confidence intervals [CIs]) for stillborn fetus associated with 5-9%, 10
      19%, 20-29%, 30-39%, and 40% or more birth weight discordance, respectively, were
      0.81 (95% CI 0.58, 1.11), 1.41 (95% CI 1.07, 1.84), 1.74 (95% CI 1.28, 2.35),
      3.06 (95% CI 2.21, 4.24), and 4.29 (95% CI 3.05, 6.04) for smaller twins. The
      corresponding ORs (95% CIs) for larger twins were 0.78 (95% CI 0.57, 1.08), 1.26
      (95% CI 0.96, 1.66), 1.77 (95% CI 1.27, 2.46), 3.38 (95% CI 2.33, 4.92), and 2.91
      (95% CI 1.89, 4.47). Similar associations were observed among smaller but not
      larger twins of opposite sex. Among larger but not smaller twins of the same sex,
      increasing birth weight discordance was associated with overall neonatal deaths.
      This association was not apparent among smaller and larger twins of opposite sex.
      However, increasing birth weight discordance was associated with neonatal deaths
      related to congenital malformations among smaller and larger twins. CONCLUSION:
      The results provide evidence that increased twin birth weight discordance was
      associated with increased risk of intrauterine death and malformation-related
      neonatal deaths.

PMID- 12220767
TI  - Young maternal age associated with increased risk of postneonatal death.
AB  - OBJECTIVE: To determine whether full-term, healthy infants born to early
      adolescent mothers (15 years old and younger) are at higher risk of postneonatal
      death compared with infants of adult mothers. METHODS: We combined the
      comprehensive 1996 and 1997 United States birth cohorts to compare postneonatal
      mortality rates among maternal age groups. With postneonatal death as our main
      outcome measure, we used multivariable logistic regression to model adjusted odds
      ratios. RESULTS: The postneonatal mortality rate for infants born to mothers 15
      years old and younger was substantially higher (3.2 per 1000) than that of
      infants born to mothers 23-29 years old (0.8 per 1000) and remained substantially
      higher after adjusting for maternal race or ethnicity. Even after adjusting for
      maternal race or ethnicity, prenatal care utilization, and marital status,
      infants born to early adolescent mothers had a three-fold higher risk (odds ratio
      3.0, 95% confidence interval 2.5, 3.6) of postneonatal death compared with adult
      mothers. CONCLUSION: Healthy infants born to early adolescent mothers are at
      increased risk of postneonatal death. Many of these deaths are potentially
      preventable; therefore, developing targeted postnatal support services
      specifically designed to address the needs of healthy infants born to adolescent
      mothers might have a positive effect on the lives of these children.

PMID- 12220768
TI  - KUR-1246, a novel beta(2)-adrenoceptor agonist, as a tocolytic agent.
AB  - OBJECTIVE: To examine the effects of KUR-1246 on oxytocin-induced uterine
      contractions, the cardiovascular system, and general metabolism of pregnant sheep
      and their fetuses. METHODS: At 123-125 days' gestation, ewes (n = 8) were infused
      with oxytocin (1.0 mU/kg/minute) to induce uterine contractions. One hour later,
      KUR-1246 was infused for 3 consecutive hours beginning at a dose of 0.001
      microg/kg/minute for 30 minutes and increasing stepwise every 30 minutes to 0.3
      microg/kg/minute in the KUR-1246 group (n = 4). The control received saline
      instead (n = 4). Statistical comparisons of changes with time in the physiologic
      parameters between the two groups were carried out (analysis of variance).
      RESULTS: KUR-1246 suppressed oxytocin-induced uterine contractions more than 90%
      at doses over 0.03 microg/kg/minute. Significant differences between the two
      groups were found at high doses over 0.03 microg/kg/minute for the following
      parameters: maternal heart rate, diastolic blood pressure, mean blood pressure,
      base excess, blood K(+), blood lactate, plasma glucose, plasma insulin, plasma
      nonesterified fatty acid levels, and fetal plasma glucose and plasma insulin
      levels. CONCLUSION: KUR-1246 significantly inhibited oxytocin-induced uterine
      contractions at doses over 0.03 microg/kg/minute and showed reduced
      cardiovascular and metabolic side effects compared with ritodrine hydrochloride
      studied earlier in pregnant sheep.

PMID- 12220769
TI  - Flaxseed dietary supplement versus hormone replacement therapy in
      hypercholesterolemic menopausal women.
AB  - OBJECTIVE: To assess serum lipid changes by a phytoestrogen dietary supplement
      compared with oral estrogen-progesterone replacement in hypercholesterolemic
      menopausal women. METHODS: Twenty-five menopausal patients with total cholesterol
      greater than 6.2 mmol/L (240 mg/dL), a cholesterol/high-density lipoprotein
      cholesterol ratio greater than 4.5 and triglycerides less than 3.5 mmol/L (310
      mg/dL) after a 4-month diet, were randomized to add 40 g/day of crushed flaxseed
      to their diet or to take daily 0.625 mg of conjugated equine estrogens alone
      (hysterectomy, n = 10) or combined with 100 mg of micronized progesterone (intact
      uterus, n = 15). After 2 months of treatment, both groups continued the diet
      alone during a 2-month washout period before crossing over to the alternate
      treatment for 2 more months. RESULTS: Differences were found between hormone
      replacement therapy and flaxseed respectively for decrease of low-density
      lipoprotein cholesterol (3.8 +/- 0.2 versus 4.4 +/- 0.2 mmol/L) (148 +/- 8 versus
      170 +/- 8 mg/dL) (P =.10), increase of high-density lipoprotein cholesterol (1.6
      +/- 0.04 versus 1.3 +/- 0.03 mmol/L) (62 +/- 1 versus 50 +/- 1 mg/dL) (P =.001),
      and increase of apolipoprotein A-1 (1.71 +/- 0.07 versus 1.42 +/- 0.05 g/L) (P
      =.003). These changes were not related to modifications in diet, exercise, or
      anthropometric measurements evaluated in parallel. Both treatments produced
      similar decreases in menopausal symptoms and in glucose and insulin levels. Only
      hormone replacement therapy as compared with flaxseed induced an elevation of sex
      hormone binding globulin (P =.004), lowered fibrinogen (P =.08), and plasminogen
      activator inhibitor type 1 (P =.01). CONCLUSION: Although 40 g of flaxseed is as
      effective as oral estrogen-progesterone to improve mild menopausal symptoms and
      to lower glucose and insulin levels, only hormone replacement therapy
      significantly improves cholesterol profile in hypercholesterolemic women and
      favorably modifies markers related to cardiovascular health.

PMID- 12220770
TI  - Presumed diagnosis of ectopic pregnancy.
AB  - OBJECTIVE: To evaluate the accuracy of the diagnosis of presumed ectopic
      pregnancy. METHODS: This was a retrospective cohort analysis at a tertiary care
      medical center. The patient population was composed of 1) clinically stable
      pregnant women with human chorionic gonadotropin (hCG) above 2000 mIU/mL and no
      evidence of an intrauterine pregnancy by ultrasound, or 2) women with an abnormal
      rise or fall of serial hCG below 2000 mIU/mL. Outcome was determined by
      pathologic evidence of chorionic villi in the endometrial curettings (or
      fallopian tube), or complete resolution of hCG. RESULTS: Overall, 38.4% (43/112)
      of the women were diagnosed with a miscarriage and 61.6% (69/112) were found to
      have an ectopic pregnancy. No significant difference was found in race, age,
      gravity, parity, hCG trends, or time to diagnosis between women with ectopic
      pregnancies and those with miscarriages. Patients were more likely to be
      diagnosed with an ectopic pregnancy if the initial hCG value was below the
      discriminatory zone (relative risk 2.44; 95% confidence interval 1.07, 5.52).
      Ultrasound correlated well with the final diagnosis (P =.001) but was not
      definitive. CONCLUSION: In an effort to save time, avoid dilation and curettage
      (D&C), and treat with methotrexate, the presence of an ectopic pregnancy is often
      presumed. The presumed diagnosis of ectopic pregnancy is inaccurate in almost 40%
      of cases. A D&C is necessary to differentiate an ectopic pregnancy from a
      miscarriage before a woman is presumptively treated with methotrexate.

PMID- 12220771
TI  - The effect of interval tubal sterilization on sexual interest and pleasure.
AB  - OBJECTIVE: To determine if interval tubal sterilization leads to a change in
      female sexual interest or pleasure and to identify predictors of a positive or
      negative effect. METHODS: Our study population comprised 4576 women enrolled in a
      prospective, multicenter cohort study between 1978 and 1983. Potential
      demographic, clinical, and surgical predictors of sexual outcome were tested for
      significant variation from the overall pattern of unchanged, increased, and
      decreased sexual interest and pleasure. RESULTS: Over 80% of the 4576 study women
      reported no consistent change in either sexual interest (80.0%) or pleasure
      (81.7%) after interval tubal sterilization. Among women with consistent change,
      positive effects were reported ten and 15 times more often than negative effects
      for sexual interest and pleasure, respectively. All subgroups of women, except
      for those with poststerilization regret, were significantly (P <.05) more likely
      to experience increased rather than decreased interest or pleasure. Women with
      poststerilization regret were the subgroup most likely to have a negative effect;
      in multivariate analyses, poststerilization regret was the only factor to be a
      predictor for decreased interest (odds ratio 4.0) and decreased pleasure (odds
      ratio 5.1). Similarly, women reporting regret were significantly less likely to
      report increased interest or pleasure. Whether the regret or the decreased sexual
      interest or pleasure occurred first is unclear. CONCLUSION: Interval tubal
      ligation is unlikely to result in changed sexual interest or pleasure. Among
      those with change, the majority experienced positive sexual effects.

PMID- 12220772
TI  - Tension-free vaginal tape: a quality-of-life assessment.
AB  - OBJECTIVE: To assess whether tension-free vaginal tape (TVT) results in
      significant improvements in urinary incontinence and its effect on patients'
      quality of life (QOL) utilizing two validated questionnaires. METHODS: One
      hundred sixty-two tension-free vaginal tape procedures were performed at two
      sites between October 1998 and January 2001. All patients were requested to
      complete the Incontinence Impact Questionnaire (IIQ-7) and Urinary Distress
      Inventory (UDI-6) as part of their preoperative assessment. History, physical,
      and demographic data were also collected. All subjects underwent subtracted
      cystometry and urethral function tests prior to surgery. A combination of mail
      and phone follow-up was used to obtain postoperative IIQ-7 and UDI-6 scores in
      October 2001. Data were analyzed with the Wilcoxon matched-pairs signed-ranks
      test. RESULTS: One hundred fifty-one patients completed the pre- and
      postoperative quality-of-life forms and were included in the analysis. Mean
      follow-up was 22.1 months (range 6.1-49.8). There were significant improvements
      in postoperative scores for both the IIQ-7 and the UDI-6 (P <.001). Significant
      improvements were also seen in subscales measuring urge symptoms, stress
      incontinence symptoms, and symptoms of voiding dysfunction. These improvements
      were consistent, regardless of type or severity of stress incontinence.
      CONCLUSION: The IIQ-7 and UDI-6 are validated tools that can be used to provide
      some objective evidence for the impact of urinary incontinence on patients'
      lives. Utilizing these two validated quality-of-life tools we show that tension
      free vaginal tape results in significant improvement in patient quality of life
      and symptoms of urgency, stress incontinence, and voiding dysfunction.

PMID- 12220773
TI  - Perinatal antibiotic usage and changes in colonization and resistance rates of
      group B streptococcus and other pathogens.
AB  - OBJECTIVE: To quantify current antibiotic usage during the perinatal period and
      impact on vaginal-rectal colonizing organism resistance rates. METHODS: Swabs
      were obtained for culture of group B streptococcus and other bacteria from a
      cohort of 1207 pregnant women in Calgary, Alberta, at 36 weeks' gestation. Those
      women who received antibiotics during labor or after pregnancy and a 10% subset
      who received no antibiotics had repeat cultures at 6 weeks postpartum. Cultured
      organisms were tested for sensitivity to several antibiotics. RESULTS: Group B
      streptococcus was identified in 235 women (19.5%) in the antepartum period. Fifty
      one percent of all participants received antibiotics (31.4% intrapartum). Group B
      streptococcus prophylaxis was given to 215 (17.8%), whereas 83 (6.9%) group B
      streptococcus-negative women without fever during labor received antibiotics.
      Ampicillin (49%), cefazolin (28%), and penicillin (18%) were the most frequently
      used antibiotics. Resistance rates among group B streptococcus to erythromycin
      and clindamycin were 5.6% and 3.0%, respectively, whereas 20.6% of Escherichia
      coli were ampicillin resistant. Among antibiotic recipients, 6.3% of all bacteria
      that were initially sensitive on prenatal cultures to a specific antibiotic
      became resistant in the postnatal period, whereas 6.5% that were initially
      resistant became sensitive. CONCLUSION: Current prevention practices in our
      region were associated with perinatal antibiotic administration in over half of
      pregnant women. Ampicillin was the most common antibiotic administered. Some
      physicians are treating women who are group B streptococcus culture negative at
      term, a practice that is of no proven value. However, this was not associated
      with increased resistance for group B streptococcus or other organisms identified
      from maternal vaginal-rectal tracts.

PMID- 12220774
TI  - Intrapartum antibiotic prophylaxis 1: relative effects of recommended antibiotics
      on gram-negative pathogens.
AB  - OBJECTIVE: To assess whether the antibiotic chosen for intrapartum antibiotic
      prophylaxis affects the subsequent exposure of the neonate to ampicillin
      resistant gram-negative bacteria. METHODS: We performed a randomized clinical
      trial of ampicillin versus penicillin for intrapartum antibiotic prophylaxis.
      Genital tract cultures for Enterobacteriaceae were obtained at study entry and 8
      36 hours postpartum. Organisms were isolated, identified, and tested for
      ampicillin susceptibility. RESULTS: The ampicillin (n = 175) and penicillin (n =
      177) groups, respectively, did not differ in rates of ampicillin-resistant
      Escherichia coli at entry (25% versus 22%, P =.57) or postpartum (36% versus 38%,
      P =.64). Similarly, groups did not differ in rates of ampicillin-resistant
      Enterobacteriaceae at entry (38% versus 32%, P =.23) or postpartum (51% versus
      55%, P =.46). However, postpartum culture rates of resistant Escherichia coli
      were higher than entry culture rates for both the ampicillin (36% versus 25%, P
      =.026) and penicillin (38% versus 22%, P <.001) groups. Postpartum culture rates
      of resistant Enterobacteriaceae were also higher than entry culture rates for
      both the ampicillin (51% versus 38%, P <.001) and penicillin (55% versus 32%, P
      <.001) groups. Results were similar when considering only women who received two
      or more doses and no additional antibiotics. CONCLUSION: Intrapartum antibiotic
      prophylaxis with either ampicillin or penicillin increases exposure of neonates
      to ampicillin-resistant Enterobacteriaceae.

PMID- 12220775
TI  - Intrapartum antibiotic prophylaxis 2: positive predictive value of antenatal
      group B streptococci cultures and antibiotic susceptibility of clinical isolates.
AB  - OBJECTIVE: To estimate the probability of positive intrapartum group B
      streptococcus cultures among women previously identified as carriers of this
      organism, and to estimate the susceptibility of group B streptococci to six
      commonly used antibiotics. METHODS: We performed a prospective cohort study of
      women identified as carriers of group B streptococci by current pregnancy genital
      tract (group 1) or urine cultures (group 2), or a positive culture in a prior
      pregnancy (group 3). Intrapartum culture specimens were obtained, and isolates
      were tested for susceptibility to six antibiotics using the agar disk diffusion
      technique. RESULTS: Intrapartum cultures were positive for 68% (62, 73), 61% (49,
      72), and 48% (36, 60) of groups 1 (n = 249), 2 (n = 69), and 3 (n = 59),
      respectively. Cultures were positive in 67% (61, 73) of women in group 1 whose
      cultures were done 42 days or less before delivery (n = 218). The proportion of
      isolates (n = 239) susceptible to penicillin, ampicillin, cefazolin, and
      vancomycin was 100% (98, 100). The proportion susceptible to clindamycin and
      erythromycin was 91% (87, 94) and 79% (73, 84), respectively. CONCLUSION: The
      positive predictive value of antenatal group B streptococci cultures is lower
      than was previously reported. Clindamycin and erythromycin are not optimal agents
      for prophylaxis against early-onset neonatal group B streptococcal infection in
      patients who are allergic to penicillin.

PMID- 12220776
TI  - Pulsed-field fingerprinting of vaginal group B streptococcus in pregnancy.
AB  - OBJECTIVE: There is more to be learned about the epidemiology of group B beta
      hemolytic streptococci infections in pregnancy. In this study, we investigated
      the discriminating capabilities of pulsed-field gel electrophoresis of group B
      streptococci strains from pregnant patients and mother/infant pairs of patients
      compared with serotyping. METHODS: Forty-two vaginal strains of group B
      streptococci cultured from pregnant patients in the third trimester and strains
      from 20 mother/infant pairs with documented newborn group B streptococci
      infection were studied. Isolates were serotyped by the Lancefield capillary
      precipitin method and molecularly characterized by counterclamped homogeneous
      electrical field pulsed-field gel electrophoresis with rarely cutting restriction
      enzymes. RESULTS: Nine of the 13 serotypes of group B streptococci identified
      thus far in the scientific literature (Ia, Ia/c, Ib, Ib/c, II, IIc, III, V, and
      NT/c) were represented among the 62 isolates. Among the 42 maternal isolates,
      eight serotypes were represented, and among the 20 mother/infant isolates, six
      serotypes were represented. Serotypes of mother/infant isolates matched in nine
      of the ten pairs. Restriction endonuclease profiles, or digests, from the 42
      maternal isolates resulted in 25 unique profiles that were arranged into five
      major groups based on the overall relatedness. Each group was comprised of one
      predominant serotype. The 20 mother/infant paired isolates displayed nine unique
      restriction endonuclease profiles and nine of the ten paired isolates showed
      indistinguishable restriction endonuclease profiles between mother and infant.
      CONCLUSION: Deoxyribonucleic acid profiling using pulsed-field gel
      electrophoresis is more discriminating of group B streptococci strains than
      serotyping because of the different yet closely related patterns within each
      restriction endonuclease profile group that are linked to one specific serotype.
      Pulsed-field gel electrophoresis can refine our epidemiologic studies of group B
      streptococci transmission and acquisition.

PMID- 12220777
TI  - Human chorionic gonadotropin and testosterone in normal and preeclamptic
      pregnancies in relation to fetal sex.
AB  - OBJECTIVE: The aim of the present study was to evaluate the effects of fetal
      gender on serum human chorionic gonadotropin (hCG) and testosterone in
      normotensive and preeclamptic pregnancies. METHODS: The study consisted of 137
      women with singleton pregnancies in the third trimester. Seventy-three
      pregnancies were uncomplicated; among those were 35 male and 38 female fetuses.
      Sixty-four pregnancies were complicated by preeclampsia; among those were 33 male
      and 31 female fetuses. Human chorionic gonadotropin and total testosterone were
      measured in maternal peripheral blood. RESULTS: In male-bearing pregnancies,
      maternal hCG and testosterone serum levels were significantly higher in
      preeclamptic than normotensive mothers (P <.001). In female-bearing pregnancies,
      testosterone levels were significantly higher in preeclamptic than normotensive
      mothers (P <.001), whereas the hCG levels were not significantly different. Male
      bearing preeclamptic women had significantly higher testosterone levels than
      female-bearing preeclamptic women (P <.02), whereas the hCG levels were not
      significantly different. In uncomplicated pregnancies the hCG levels were
      significantly higher in female-bearing than in male-bearing mothers (P <.005),
      whereas the testosterone levels were not significantly different. CONCLUSION: In
      preeclamptic pregnancies with male fetuses, the maternal serum hCG levels were
      significantly higher than in uncomplicated pregnancies. Total testosterone levels
      were significantly higher in pregnancies with either gender and significantly
      higher in male-bearing than in female-bearing pregnancies. This may indicate an
      androgen influence on the pathophysiologic mechanism of preeclampsia.

PMID- 12220778
TI  - The correlation of seizures in newborn infants with significant acidosis at birth
      with umbilical artery cord gas values.
AB  - OBJECTIVE: To correlate umbilical blood gas variables with neonatal seizures in
      neonates with significant acidosis at birth (pH < or = 7.1). METHODS: We reviewed
      the maternal and neonatal charts of 238 patients at a gestational age of 32 weeks
      or more with cord gases done at delivery and an umbilical artery pH of 7.1 or
      less. All infants transferred to the neonatal intensive care unit were studied,
      and those with neonatal seizures secondary to hypoxic ischemic encephalopathy
      were identified. We used the perinatal outcome of early neonatal seizures
      secondary to hypoxic ischemic encephalopathy to divide the patients into two
      groups. The relationship between the umbilical artery parameters of pH, base
      deficit, partial oxygen pressure (pO(2)), partial carbon dioxide pressure
      (pCO(2)), and the neonatal outcome of seizures were determined with Student t
      tests and multiple logistic regression analysis. RESULTS: Umbilical artery base
      deficit, pO(2), and pCO(2) were significantly elevated in newborns who had
      seizures, whereas cord pH was decreased. Using multiple regression analysis the
      variable neonatal seizure was predicted only by low umbilical artery pH. A pH of
      less than 7 was more sensitive (73.8%) than a base excess of -16 (52.5%) in
      predicting the development of neonatal seizures. CONCLUSION: Our data suggest
      that severe fetal acidemia identified by a pH less than 7.0 was the most
      important umbilical blood gas variable for predicting early onset of neonatal
      seizures.

PMID- 12220779
TI  - Monochorionic high-order multiple pregnancies and multifetal pregnancy reduction.
AB  - OBJECTIVE: To study the frequency and obstetric outcome of monochorionic multiple
      pregnancies in a population referred for fetal reduction. METHODS: Data charts of
      all patients with multifetal (> or =3) pregnancies referred for fetal reduction
      over the last 10 years were reviewed for the presence of monochorionic twin pairs
      or triplets. RESULTS: Twenty-nine of 239 high-order multiple pregnancies
      contained a monochorionic component (12.1%), eight of which were monochorionic
      triplets. Half of all naturally conceived pregnancies contained a monochorionic
      component. High-order multiple pregnancies with a monochorionic component
      resulted significantly more frequently from natural conceptions (7 of 29) than
      multichorionic pregnancies (7 of 210) (P =.001). Fetal reduction of the
      monochorionic twin pair in 21 pregnancies resulted in eight twin and 13 singleton
      pregnancies; mean gestational age at delivery was, respectively, 34.3 +/- 2.9 and
      39.2 +/- 1.4 weeks. Pregnancy loss rate was one of 21 (4.8%). In the remaining
      eight multiple pregnancies with a monochorionic triplet present, three were
      complicated by a twin reversed arterial perfusion sequence, and two couples
      requested a first trimester termination of pregnancy. Fetal reduction of the
      monochorionic triplet in a dichorionic quadruplet pregnancy resulted in a normal
      pregnancy outcome. In two monochorionic triplet pregnancies, fetal reduction to
      monochorionic twin pregnancies with bipolar coagulation of the umbilical cord
      resulted in a favorable pregnancy outcome. CONCLUSION: Monochorionic twins or
      triplets are frequently part of naturally conceived high-order multiple
      pregnancies. Reduction of the monochorionic twin pairs improves pregnancy
      outcome. Monochorionic triplet pregnancies show a high complication rate, but may
      benefit from fetal reduction by cord coagulation.

PMID- 12220780
TI  - Transforming growth factor-beta1 in fetal serum correlates with insulin-like
      growth factor-I and fetal growth.
AB  - OBJECTIVE: To estimate whether transforming growth factor-beta1 in fetal serum
      obtained by umbilical cord sampling at delivery is correlated with fetal growth.
      We also estimated whether transforming growth factor-beta1 is correlated with
      insulin-like growth factor-I and insulin-like growth factor binding protein-1,
      which have been shown to correlate with fetal growth. METHODS: The active form of
      transforming growth factor-beta1 was analyzed in serum from cord blood from 68
      fetuses by the enzyme-linked immunosorbent assay technique. Of the 68 pregnant
      women, 12 had preeclampsia, 14 had preeclampsia and intrauterine growth
      restriction, 15 had intrauterine growth restriction alone, and seven had fetuses
      that were large for gestational age (LGA). Twenty pregnancies with fetuses
      appropriate for gestational age (AGA) served as controls. RESULTS: Transforming
      growth factor-beta1 concentrations were significantly correlated with birth
      weight. The average transforming growth factor-beta1 concentration in the
      following groups were: intrauterine growth restriction, 22.4 +/- 2.7 microg/L;
      intrauterine growth restriction plus preeclampsia, 22.9 +/- 2.0 microg/L;
      preeclampsia without intrauterine growth restriction, 28.8 +/- 2.1 microg/L; LGA,
      30.3 +/- 4.3 microg/L; and AGA, 36.8 +/- 2.0 microg/L. Transforming growth factor
      beta1 levels were significantly lower in pregnancies complicated by intrauterine
      growth restriction and showed a positive correlation with birth weight (r = 0.48,
      P <.001). Furthermore, there was a positive correlation between insulin-like
      growth factor-I levels and birth weight (r = 0.36, P <.01) and a negative
      correlation between insulin-like growth factor binding protein-1 and birth weight
      (r = -0.32, P <.01). There was also a correlation between transforming growth
      factor-beta1 and insulin-like growth factor-I (r = 0.29, P <.05) and between
      transforming growth factor-beta1 and insulin-like growth factor binding protein-1
      (r = -0.25, P <.05). CONCLUSION: Transforming growth factor-beta1 might be
      related to fetal growth in pregnancy. The results also support previous data
      showing that insulin-like growth factor-I and insulin-like growth factor binding
      protein-1 are related to fetal growth.

PMID- 12220781
TI  - Vaginal uterine artery ligation avoids high blood loss and puerperal hysterectomy
      in postpartum hemorrhage.
AB  - OBJECTIVE: To describe a novel, effective, and minimally invasive surgical
      technique for avoiding excess blood loss and hysterectomy in intractable
      postpartum hemorrhage. Previously described techniques-uterine artery ligation at
      various levels, hypogastric (internal iliac) artery ligation, uterine compression
      all require an abdominal approach. METHODS: This procedure, which is quickly
      learned, is performable in the delivery room with minimal preparation, with or
      without bladder retraction. A 2-cm horizontal incision is made in the anterior
      cervix 1 cm beneath the estimated vaginocervical fold and the bladder reflected
      in the natural plane. Firm but gentle downward traction on the uterus to the
      contralateral side of the intended ligature maximizes cephalad and lateral
      access, permitting bilateral uterine artery ligation from laterally under direct
      vision and/or indirect transcervical palpation. RESULTS: Between November 1997
      and June 2001, 13 women with intractable postpartum hemorrhage chose the vaginal
      route over laparotomy as a uterus-preserving procedure. Hysterectomy proved
      necessary in only one case (8%) because of placenta percreta. One woman has since
      delivered a healthy term infant by cesarean, and uterine vascularization was
      unimpaired. CONCLUSION: The vaginal route offers a novel, simple, effective, and
      minimally invasive technique for treating intractable puerperal hemorrhage by
      uterine artery ligation. Timely intervention avoids hysterectomy and consumption
      coagulopathy and preserves reproductive potential.

PMID- 12220782
TI  - Predicting chlamydial and gonococcal cervical infection: implications for
      management of cervicitis.
AB  - OBJECTIVE: To define utility of age and cervical findings in predicting infection
      with Chlamydia trachomatis and Neisseria gonorrhoeae among women universally
      tested for both infections, and to assess the independent contribution of Gram
      stain (GS) smear of endocervical secretions. METHODS: Visits by women to Seattle
      sexually transmitted diseases clinics from 1995 through 1999 were retrospectively
      reviewed. All women had endocervical GS and cultures for C trachomatis and N
      gonorrhoeae performed. Predictive values of age, cervical signs, and inflammation
      on GS (more than 30 polymorphonuclear leukocytes per 1000x field) were
      calculated. RESULTS: Among 6230 women, prevalence of C trachomatis and N
      gonorrhoeae was 6.9% and 2.1%, respectively; 520 women (8.3%) had either organism
      detected. Age, cervical signs (mucopus, induced bleeding), and inflammation on
      endocervical GS were independently associated with infection. However, the
      positive predictive value (PPV) of any cervical finding for infection was less
      than 19% in women 25 years and older. Inflammation on endocervical GS was the
      sole indicator of infection in 79 of 520 (15%) infections, but was insensitive in
      the absence of mucopurulent cervicitis (sensitivity, 26%; PPV, 21%). CONCLUSION:
      Cervical signs suggesting chlamydial or gonococcal infection have higher positive
      predictive value (PPV) in younger women. The PPV of inflammation on endocervical
      GS is too low to recommend its use to direct empiric treatment in the absence of
      mucopurulent cervicitis, especially in women 25 years and older. Further, its low
      sensitivity in detecting infection in women without mucopurulent cervicitis does
      not justify routine use. Signs suggesting mucopurulent cervicitis should be
      interpreted in the context of age, and empiric treatment may not be indicated in
      women aged 25 years and older.

PMID- 12220783
TI  - Efficacy, cycle control, and user acceptability of a novel combined contraceptive
      vaginal ring.
AB  - OBJECTIVE: To assess the contraceptive efficacy, cycle control, tolerability, and
      user acceptability of a novel combined contraceptive vaginal ring for up to 13
      cycles. METHODS: Healthy women requesting contraception were enrolled in this 1
      year multicenter study. Each ring released 120 microg of etonogestrel and 15
      microg of ethinylestradiol daily, and was used for 3 weeks followed by a 1-week
      ring-free period. RESULTS: A total of 2322 women started treatment and so formed
      the intent-to-treat population. Subjects were followed for 23,298 cycles,
      equivalent to 1786 woman-years. Compliance was good with 85.6% of cycles in full
      compliance with specified criteria. In the intent-to-treat population, 21
      pregnancies occurred, giving a Pearl Index of 1.18 (95% confidence interval 0.73,
      1.80). Eleven of the pregnancies were attributable to noncompliance; the Pearl
      Index for the per-protocol population was 0.77 (95% confidence interval 0.37,
      1.40). The mean incidence of withdrawal bleeding was 98.5% in all cycles.
      Irregular bleeding occurred in 5.5% of all cycles, and in most women, early or
      late withdrawal bleeding was restricted to spotting. The ring was well tolerated
      with a low incidence of adverse events; only 2.5% of all discontinuations were
      device related. The ring was easy to insert and remove and did not interfere with
      intercourse. Eighty-five percent of women were satisfied with the ring, and 90%
      would recommend its use to others. CONCLUSION: The ring is an effective
      contraceptive with excellent cycle control that is convenient, well tolerated,
      and highly acceptable to users.

PMID- 12220784
TI  - Pharmaceutical sales representatives and the doctor/patient relationship.
AB  - As marketing efforts by drug companies become more aggressive, physicians are
      being asked to provide clinical "preceptorships" to pharmaceutical sales
      representatives. During a "preceptorship" of this type, the company
      representative spends a day with the physician seeing patients "as an educational
      experience," and the physician receives an "honorarium" from the drug company in
      return. We explore the implications of this practice. First, we examine the
      nature of the doctor/patient relationship and the fiduciary obligations incumbent
      upon physicians in their role as healers. Second, we examine four interlocking
      ethical principles-nonmaleficence, beneficence, respect for patient autonomy, and
      justice-that should govern doctor/patient encounters. Third, we critique several
      hypothetical scenarios involving individuals who might put forth a claim to enter
      the doctor/patient relationship (ie, a pharmacist, a social scientist, the
      husband of the patient, and a pharmaceutical sales representative). We conclude
      that the practice of providing clinical "preceptorships" to pharmaceutical sales
      representatives is unjustifiable, is unethical, and should not be permitted.

PMID- 12220785
TI  - Management of rhesus alloimmunization in pregnancy.
AB  - Hemolytic disease of the newborn secondary to rhesus alloimmunization was once a
      major contributor to perinatal morbidity and mortality. Today, rhesus immune
      globulin has markedly decreased the prevalence of this disease so that only one
      to six cases occur in every 1000 live births. The rarity of this condition
      warrants consideration of consultation or referral to a maternal-fetal medicine
      specialist. Once sensitization occurs, rhesus immune globulin is no longer
      effective. Evaluation for the presence of maternal anti-D antibody should be
      undertaken at the first prenatal visit. First-time sensitized pregnancies are
      followed with serial maternal titers and, when necessary, serial amniocenteses to
      detect fetal bilirubin by DeltaOD(450). In cases of a heterozygous paternal
      genotype, new deoxyribonucleic acid techniques now make it possible to diagnose
      the fetal blood type through amniocentesis or even from plasma/serum
      deoxyribonucleic acid analysis. When there is a history of an affected fetus or
      infant, maternal titers are no longer diagnostic as a screening test. Serial peak
      middle cerebral artery velocities using Doppler ultrasound can be used in these
      pregnancies to detect fetal anemia. In some situations, intrauterine transfusion
      is necessary through ultrasound-directed puncture of the umbilical cord with the
      direct intravascular injection of red cells. Perinatal survival rates of more
      than 90% have been reported; hydrops fetalis reduces the chance for a viable
      outcome by up to 25%. Immediate neonatal outcome is complicated by the need for
      repeated transfusions secondary to suppressed erythropoiesis. Long-term studies
      have revealed normal neurologic outcomes in more than 90% of cases. Future
      therapy will involve selective modulation of the maternal immune system making
      the need for intrauterine transfusions a rarity.

PMID- 12220786
TI  - What's a smart woman like you doing at home?

PMID- 12220788
TI  - What's a smart woman like you doing at home?

PMID- 12220789
TI  - A breach with a breech.

PMID- 12220790
TI  - Complications associated with optical-access laparoscopic trocars.

PMID- 12220792
TI  - ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrcian
      Gynecologists: Number 38, September 2002. Perinatal care at the threshold of
      viability.
AB  - The survival rate for extremely preterm or extremely low-birth-weight (LBW)
      newborns born at the threshold of viability (25 or fewer completed weeks of
      gestation) improved in the early 1990s, largely as the result of a greater use of
      assisted ventilation in the delivery room and surfactant therapy. Increased use
      of antenatal and neonatal corticosteroids also may have influenced survival
      rates. However, this improvement in survival has not been associated with an
      equal improvement in morbidity. The incidence of chronic lung disease, sepsis,
      and poor growth remains high and may even have increased. There is concern that
      the treatment of extremely preterm and extremely LBW newborns may result in
      unforeseen effects into adulthood, and that the neurodevelopmental outcome and
      cognitive function of extremely preterm and extremely LBW infants may be
      suboptimal. The purpose of this document is to describe the potential
      consequences of extremely preterm birth and to provide clinical management
      guidelines based on the best available data.

PMID- 12220793
TI  - ACOG Committee Opinion: Number 275, September 2002. Obstetric management of
      patients with spinal cord injuries.
AB  - Effective rehabilitation and modern reproductive technology may increase the
      number of women considering pregnancy who have spinal cord injuries (SCIs). It is
      important that obstetricians caring for these patients are aware of the specific
      problems related to SCIs. Autonomic dysreflexia is the most significant medical
      complication seen in women with SCIs, and precautions should be taken to avoid
      stimuli that can lead to this potentially fatal syndrome. Women with SCIs may
      give birth vaginally, but when cesarean delivery is indicated, adequate
      anesthesia (spinal or epidural if possible) is needed.

PMID- 12220794
TI  - Cardiac drug-psychotropic drug update.
AB  - This is an update from the report-Cardiac Drug and Psychotropic Drug
      Interactions: Significance and Recommendations-published in this journal in
      November-December 1999. As mentioned in that article there has been an explosion
      of new drugs both in psychiatry and cardiology without a sufficient understanding
      of their potential interactions. Also there is a need for methods to update drug
      interactions on an ongoing basis. This report describes: 1) examples of actual
      adverse interactions from clinical cases that move beyond some of the
      hypothesized contraindications included in the 2000 millennium publication; 2)
      confirmation of previous adverse interactions reported if they strengthen the
      earlier findings; 3) listing of new drugs, e.g., sildenafil (viagra) now commonly
      prescribed by psychiatrists and cardiologists; 4) reports explaining and/or
      refining mechanisms of adverse interactions; and 5) cautions and important
      associated phenomenon of either a cardiac or a psychotropic drug, e.g., valproic
      acid and cases of life-threatening pancreatitis. Methods of publicizing the new
      knowledge of cardiac drug-psychotropic drug interactions, e.g., the Internet and
      web sites are described.

PMID- 12220795
TI  - Neurologic drug-psychotropic drug update.
AB  - It is essential that both the neurologist and the psychiatrist be aware of the
      neurology drug-psychotropic drug interactions because neurologists prescribe many
      psychotropic medications and psychiatric consultants often recommend the use of
      psychotropic drugs for neurology patients. Six methods of examining drug-drug
      interactions were employed: 1) PubMed (MEDLINE); 2) Hanston's Drug Interaction
      Analysis and Management Text (July 2001 quarterly updated version); 3)Drug
      Interactions Facts (quarterly updated version through July 2001); 4) Micromedex
      Drug-dex; 5) American Hospital Formulary Service Drug Information; 6) Food and
      Drug Administration (MedWatch) Dear Doctor Letters and new labeling. Over eighty
      important interactions of significance level 1 (major), or significance level 2
      (minor) were found. Furthermore, over one-third of the neurologist's most
      commonly administered medications were those also employed by the psychiatrist,
      but not necessarily for the same reason, e.g., carbamazepine, for seizure control
      (neurologist) or mood stabilization (psychiatrist).

PMID- 12220796
TI  - Comparison of three methods for identifying medical drug-psychotropic drug
      interactions.
AB  - Three methods for examining drug-drug interactions were compared to understand
      advantages and disadvantages of each: ePocrates; Interact; The Mount Sinai
      multiple source for the evaluation of drug-drug interactions (MS). ePocrates is a
      commonly employed software system utilized in a hand held computer, the
      PalmPilot. Interact is on a CD-ROM, and promoted by the American Psychiatric
      Association Press. The MS system was developed by the authors and utilizes six
      separate references sources to ascertain the presence and significance of drug
      drug interactions. Commonly prescribed neurology and psychotropic medication
      interactions were compared using the three systems. ePocrates did not list the
      significance level of the interaction, e.g., (major, moderate, minor), often did
      not include a mechanism of action, and several commonly employed medications were
      not included. It did permit examining several drugs at the same time, and was
      easily carried on the person of the physician. Interact often contained old
      references, several drugs were not included, was not adapted to a hand held
      computer format, and had no update since 1999. The MS system listed level of
      significance, provided mechanism of action, and advice to the practitioner
      including recommendations. It is not portable, requiring a laptop or desk top
      computer or hard copy, and only searches one drug at a time. It is hoped that the
      advantages of each of these three systems may be incorporated into systems of the
      future.

PMID- 12220797
TI  - Predictors of willingness to consider medication and psychosocial treatment for
      panic disorder in primary care patients.
AB  - The purpose of this investigation was to identify demographic and clinical
      patient characteristics related to willingness to consider panic disorder
      treatments in the primary care setting. Given the prevalence of anxiety disorders
      and the increased provision of mental health treatments in general medical
      settings, patients were selected from primary care settings. An unselected sample
      of 4,198 patients completed a brief questionnaire containing questions about
      demographic characteristics, physical health status, and symptoms of panic
      disorder, social phobia and PTSD. The 1,043 patients indicating a recent panic
      attack episode answered additional questions about their willingness to consider
      both medication and psychosocial forms of intervention for panic. Of these panic
      patients, 64% reported willingness to consider medication and 67% reported
      willingness to consider a psychosocial intervention for their panic. Logistic
      regression analyses for these panic patients revealed that willingness to
      consider medication treatment for panic was associated with older age, lower
      education, poorer health status and the presence of social phobia and/or PTSD
      symptoms. In addition, Asian and African American patients were less likely than
      Caucasian patients to indicate willingness to consider medication treatment for
      their panic. However, only the presence of comorbid social phobia and PTSD
      symptoms predicted willingness to consider a psychosocial intervention. Results
      suggest that acceptability of psychosocial treatment is unrelated to demographic
      and physical health factors, while primary care patients with certain demographic
      characteristics, good physical health, or who suffer from fewer comorbid mental
      health conditions may need additional encouragement to begin medication treatment
      for panic.

PMID- 12220798
TI  - Determinants of the diagnosis of psychological problems by primary care
      physicians in patients with normal GHQ-28 scores.
AB  - In studies comparing the performance of psychometric instruments and general
      practitioners in the identification of psychological disorders, authors usually
      treat the psychometric instrument as the gold standard. Some patients may have no
      psychiatric diagnosis and normal scores on self-report measures of distress, but
      still benefit from detection and treatment of their psychosocial problems.
      However, physicians may be spending valuable time identifying problems in
      patients who have no disability. The extent and implications of the discrepancy
      between clinician assessment and standard instruments requires further
      exploration. Adult patients of 40 family physicians completed the General Health
      Questionnaire (GHQ-28) before their visit. Immediately following the visit,
      physicians, who were blind to the patient's GHQ score, indicated whether they had
      detected any signs or symptoms of anxiety, depression, somatization, or other
      psychosocial problems. Of the 1,011 primary care patients that participated, 439
      had normal GHQ-28 scores. Physicians detected psychological problems in 177
      (38.3%) of the 439. In bivariate analyses, poorer general and mental health (as
      measured by SF-36) was associated with higher detection rates. The patient's
      belief that there was a psychological component of his or her problem (OR=2.50),
      being in a marital relationship (OR=1.87), and the physician's perception of the
      seriousness of the problem (OR=1.84) were associated with detection. Detection
      was less frequent when the physician did not know the patient well (OR=0.69), and
      when the physician was a woman (OR=0.46). For the 28% of patients who themselves
      perceived a psychological element of their problem, physician detection was
      probably appropriate. However, it is unlikely that detection of the remaining
      patients was beneficial to the patients.

PMID- 12220799
TI  - Course of depression, health services costs, and work productivity in an
      international primary care study.
AB  - The Longitudinal Investigation of Depression Outcomes (LIDO) Study examined the
      outcomes and economic correlates of previously untreated depression among primary
      care patients in Barcelona, Spain; Be'er Sheva, Israel; Melbourne, Australia;
      Porto Alegre, Brazil; St. Petersburg, Russia; and Seattle, USA. Across all sites,
      968 patients with current depressive disorder completed assessments of depression
      severity (Composite International Diagnostic Interview and Center for
      Epidemiologic Studies Depression Scale) at baseline and 9 months, and assessments
      of health services utilization and work days missed at baseline, 9 months, and 12
      months. Follow-up depression status was characterized as persistent depression
      (n=345), partial remission (n=283), or full remission (n=340). At each site,
      patients with more favorable depression outcomes had fewer days missed from work;
      however, this relationship did not reach the 5% level of statistical significance
      at any site, and reached the 10% significance level only at Porto Alegre.
      Patients with more favorable depression outcomes also had lower health services
      costs, but this relationship reached the 5% significance level only in St.
      Petersburg. While the lack of statistical precision does not permit definitive
      conclusions, our findings are consistent with recent studies showing that
      recovery from depression is associated with lower health services costs and less
      time missed from work due to illness.

PMID- 12220800
TI  - The reactions to research participation questionnaires for children and for
      parents (RRPQ-C and RRPQ-P).
AB  - Systematic assessment of the effect of clinical research studies on child and
      parent participants has been limited. Such assessment could provide an empirical
      basis for the ethical conduct of research, assisting investigators and
      institutional review boards in balancing the need for sound research with the
      need to protect study participants. The Reactions to Research Participation
      Questionnaire for Children (RRPQ-C) and the RRPQ for Parents (RRPQ-P) are brief
      measures designed to assess child or parent views of clinical research studies.
      Both measures were piloted and then administered as part of an interview-based
      study of traumatically injured children and their parents, to assess their
      psychometric properties and potential usefulness as addenda to future study
      protocols. The RRPQ-C and RRPQ-P each demonstrated acceptable internal
      consistency. Exploratory factor analyses provided general support for their
      conceptual basis. Both were easily administered and well-accepted by respondents.
      There is evidence that children and adults were willing to answer honestly, even
      about negative responses. Brief measures such as the RRPQ-C and RRPQ-P may
      provide a practical and empirically informed method for assessing children's and
      parents' responses to research participation. Investigators should consider
      including systematic standardized assessment of participant reactions in child
      clinical research studies.

PMID- 12220801
TI  - Reporting psychosomatic consultations in the discharge letter: an examination of
      communication between inpatient and primary care physicians.
AB  - The discharge letter is the primary means of communication between the inpatient
      and the outpatient treatment providers in the German health care system. The
      inclusion of psychosomatic consultation findings within the discharge letter is a
      critical step for impacting the psychosocial aspects of patient care following
      discharge. The present retrospective study measured the extent to which
      psychosomatic consultations conducted at the University of Heidelberg Medical
      Hospital were mentioned in the discharge letter during a 2-year index period.
      Psychosomatic consultations (N=605) were requested by a total of 101 inpatient
      physicians and conducted by 9 consultants. Of the 528 discharge letters that were
      reviewed, 67.8% referenced the psychosomatic consultation. Results from a
      stepwise logistic regression analysis found that a reason for referral due to
      "presumed psychiatric etiology of unexplained physical complaints" was the
      strongest predictor of whether the consultation was mentioned in the discharge
      letter (odds ratio=2.27). In contrast, a referral due to "coping and compliance
      problems" or the identification of psychosocial problems secondary to a somatic
      illness significantly decreased the chance of communication. The high rate of
      communication when physicians are confronted with a complex diagnostic picture
      involving presumed psychiatric comorbidity underscores the perceived usefulness
      of the consultation. However, consultants may need to take an active role in
      facilitating the management of psychosocial aspects of care during the inpatient
      stay and following discharge in an effort to improve concordance.

PMID- 12220802
TI  - Effect of psychiatric group intervention on natural-killer cell activity and
      pregnancy rate.
AB  - We investigated the effects of psychiatric group intervention on the emotions,
      natural-killer (NK) cell activity and pregnancy rate in Japanese infertile women
      by a randomized study. Thirty-seven women completed a 5-session intervention
      program and were compared with 37 controls. Psychological discomfort and NK-cell
      activity (47.7% to 34.1%, P<.0001) significantly decreased after the
      intervention, whereas no significant changes were observed in controls. According
      to a 1-year follow-up of both groups, the pregnancy rate in the intervention
      group was significantly higher than that of controls (37.8% vs. 13.5%, P=.03).
      Psychological group intervention was therefore effective in Japanese infertile
      women.

PMID- 12220803
TI  - Estrogen supplementation for female schizophrenics treated with atypical
      antipsychotics.
AB  - It has been suggested that estrogen supplementation can augment the treatment
      effects of typical antipsychotic medication. We report the use of estrogen
      supplementation for four female chronic inpatients. These patients were diagnosed
      with schizophrenia or schizoaffective disorders and were treated with atypical
      antipsychotics. Premenstrual exacerbation of psychiatric symptoms had been noted
      for all patients. Daily oral conjugated estrogen (Premarin 0.625 mg) was
      administered for three months continuously, and patients were assessed using the
      Nurses' Observation Scale for Inpatient Evaluation. Attenuation of premenstrual
      aggravation of psychiatric symptoms during menstruation was noted for two of the
      four cases, with substantial improvement noted for one of these. After Premarin
      treatment was discontinued, three patients were assessed as worse than the pre
      supplementation phase using the evaluation scale. This finding is suggestive of
      individual variability for response to estrogen supplementation, with a possible
      association for onset age. Caution is advised where estrogen is used to treat
      schizophrenic patients taking atypical antipsychotics.

PMID- 12220804
TI  - Handling the case of the drug and alcohol abusing bus driver.

PMID- 12220806
TI  - Transmission of encephalomyocarditis virus (EMCV) among pigs experimentally
      quantified.
AB  - Two types of transmission experiments were performed to estimate the basic
      reproduction ratio R(0), indicating the level of encephalomyocarditis virus
      (EMCV) transmission among pigs. In a first experimental set-up with nine separate
      pairs, one randomly chosen piglet per pair was inoculated with a Belgian
      (myocardial) EMCV strain (B279/95, 10(3)TCID(50)/ml oronasally) and placed back
      into the pen. In the second experiment with two separate groups of five piglets,
      two piglets in each group were inoculated at the start. During the experiments,
      viraemia in blood and excretions was measured as well as the serological response
      against EMCV antigen. After death or euthanasia, the piglets were checked for
      heart lesions and virus isolation was done on various tissues. In both the
      experiments, the majority of the inoculated piglets either died with typical
      heart lesions (five out of nine and three out of four resp.), or produced high
      levels of neutralising antibody. EMC virus was isolated from the hearts of all
      piglets that died during either one of the experiments. The pairwise experiment
      revealed a point estimate for R(0) of 2.0 (95% confidence interval (CI)=0.37
      10.74), while the group experiment resulted in a R(0)-value of 0.71 (95% CI=0.08
      4.93). Combining the information from both experiments results in an estimate for
      R(0) of 1.24 (95% CI=0.39-4.35). Since R(0) has values around the threshold value
      of 1, the spread of EMCV due to contacts between pigs will in most cases be
      limited, but due to chance processes may lead to large outbreaks as well.

PMID- 12220807
TI  - Restriction endonuclease and monoclonal antibody analysis of Brazilian isolates
      of bovine herpesviruses types 1 and 5.
AB  - Twelve Brazilian isolates and three reference strains of bovine herpesviruses
      (BHVs) were subjected to restriction endonuclease analysis (REA) and monoclonal
      antibody (MAb) analysis. Viral DNA was cleaved with BamHI, BstEII, EcoRI, HindIII
      and PstI. The monoclonal antibody panel allowed the differentiation between types
      1 and 5 viruses, while REA with BstEII and HindIII showed the distinction between
      BHV-1 and -5 subtypes. Typical 1.1 and 1.2a patterns were observed with two
      isolates from respiratory disease. An isolate from semen of a clinically healthy
      bull displayed 1.2b profile, whereas another displayed a clear 5a pattern, which
      was never reported before. Seven out of nine Brazilian type 5 (BHV-5) isolates
      displayed REA patterns similar to the Australian BHV-5 strain N569 (BHV-5a), and
      differing from the Argentinean A663 strain (BHV-5b) virus. Another two BHV-5
      isolates, which displayed an unusual MAb pattern of reactivity, showed a BstEII
      profile different from both reference strains of BHV-5. These two viruses were
      considered BHV-5 "non-a/non-b" subtype.

PMID- 12220809
TI  - Development of an ELISA using a recombinant 41 kDa partial protein (P45N') for
      the detection of Riemerella anatipestifer infections in ducks.
AB  - Riemerella anatipestifer, a gram-negative bacillus, is the causative agent of
      duck septicemia, a disease which could incur much economic loss in the duck
      industry. An indirect enzyme-linked immunosorbent assay (ELISA) has been
      developed to facilitate early detection of R. anatipestifer infection in ducks.
      The antigen used was a recombinant 41 kDa N-terminal fragment (rP45N') of a newly
      characterized R. anatipestifer potential surface protein, P45, which was
      expressed in Escherichia coli as an N-terminal GST fusion protein. The rP45N'
      based ELISA successfully detected P45 antibodies in the sera of 20 ducks
      immunized with bacterin preparations of R. anatipestifer serotypes 1, 10 15, 19
      and the ATCC11845 strain. Antibodies to P45 were also detected in the sera of 25%
      (75/296) of White Pekin ducks which were imported into Singapore from three
      different farms. Successful discrimination was obtained between sera from
      infected ducks and that of specific-pathogen free ducks (p<0.01). The rP45N'-GST
      antigen did not cross-react with antibodies in sera from guinea pigs which were
      infected with other gram-negative and gram-positive bacterial pathogens,
      including Aeromonas hydrophila, Citrobacter freundii, E. coli, Klebsiella
      pneumoniae, Pastuerella multocida, Proteus mirabilis, Salmonella spp., Serratia
      maccescens, Shigella sonnei and Yersinia enterocolitica. In addition, the DNA
      sequence encoding P45 was detected in R. anatipestifer serotypes 1, 2, 3, 4, 5,
      6, 7, 8, 9, 11, 14, 15, 16, 17, 18, 19 and the ATCC11845 strain, suggesting that
      P45 is probably also universally expressed in these R. anatipestifer serotypes.
      Thus, the ELISA described is applicable to the detection of R. anatipestifer
      infection in ducks.

PMID- 12220808
TI  - Adjuvant regulation of cytokine profile and antibody isotype of immune responses
      to Mycoplasma agalactiae in mice.
AB  - Traditionally, adjuvants have been administered with antigens to enhance
      immunity. We studied the effect of several adjuvants such as Freund's complete
      adjuvant (FCA), Freund's incomplete adjuvant (FIA), lipopolysaccharide (LPS),
      homopolymers of polyinosinic-polycytidylic acid (poly I:C) and polyadenylic
      polyuridylic acid (poly A:U), lithium chloride (LiCl), saponin Quil A and calcium
      phosphate gel (CaHPO(4)) on the immune response of mice to formalin-inactivated
      Mycoplasma agalactiae. The specific antibody or cytokine producing splenocytes
      were detected by ELISAspot and immunocytochemistry, respectively. Depending on
      the adjuvant given, the number of M. agalactiae-specific antibody producing cells
      was increased 2.5-6-fold. IgG was the major class of M. agalactiae-specific
      antibodies followed by IgM, IgA and IgE. Among IgG isotypes, FCA, FIA, Quil A and
      CaHPO(4) induced an IgG1 response with substantial increase of the IgG2a, IgG2b
      and IgG3 isotypes while poly I:C shifted the response toward an IgG2a/IgG3
      production. Finally, poly A:U induced an IgG2b response while LPS and LiCl
      augmented the IgG3/IgG1/IgG2a secretion. FCA augmented IL-4, IL-5 and IL-10
      production suggesting a strong Th2 response, while IFN-gamma and IL-12 remained
      low; poly I:C enhanced IFN-gamma, IL-12 and TNF-alpha eliciting a Th1 response;
      poly A:U resulted in a IL-10, IL-5, IL-6 and IL-12 secretion; and LPS enhanced
      the IL-10, IL-6 and TNF-alpha production. Our data show that adjuvants augment M.
      agalactiae-specific antibody production and lead to B cell isotype-switching via
      the appropriate cytokine milieu. Certain adjuvants, such as poly I:C, therefore,
      appear as promising immune enhancers for vaccination against M. agalactiae
      infections.

PMID- 12220810
TI  - Development of a capture ELISA for the detection of antibodies to
      enteropathogenic Escherichia coli (EPEC) in rabbit flocks using intimin-specific
      monoclonal antibodies.
AB  - A capture enzyme-linked immunosorbent assay (cELISA) was developed using intimin
      specific monoclonal antibodies to detect specific antibody in rabbits that have
      been in contact with enteropathogenic Escherichia coli (EPEC). Sera from 121 EPEC
      negative, minimum-disease-level (MDL) rabbits were used for negative controls,
      and sera from 25 MDL rabbits, experimentally infected with EPEC of bio-/serotype
      3-/O15, for positive controls. These were used to determine a cut-off value for a
      positive cELISA result. The value selected gave the test a sensitivity of 80.0%
      and a specificity of 98.4% on an individual level. At this value, a flock level
      sensitivity and specificity of 79.2 and 85.2%, respectively were calculated for a
      flock with a prevalence of seven per cent, if 40 animals were tested, and a
      minimum of two reactors were obtained. The test characteristics improve with
      increasing prevalence. To evaluate the diagnostic potential of the cELISA, sera
      from 40 to 50 slaughter rabbits per flock from 25 rabbit flocks with
      bacteriologically determined EPEC status were tested. The results demonstrated
      that this test can be a useful tool to determine the EPEC status of a rabbitry,
      provided that it is used at regular intervals.

PMID- 12220811
TI  - Comparative performance of tests using cytosolic or outer membrane antigens of
      Brucella for the serodiagnosis of canine brucellosis.
AB  - Although some ELISA tests using cytoplasmic or outer membrane antigens of
      Brucella have been developed to improve the diagnosis of canine brucellosis, the
      performance of these assays has not been compared. In the present study three
      ELISA tests using lipopolysaccharide (LPS)-free cytoplasmic proteins (CPs) of
      Brucella abortus, the lumazine synthase (LS) of Brucella spp. or a hot-saline
      (HS) extract of Brucella canis containing outer membrane antigens were used to
      test sera from dogs with suspected or confirmed brucellosis (n=36) and from dogs
      with pathological conditions other than brucellosis (n=212). In the first group
      the proportion of positive results was 92, 92 and 81% for the ELISAs with HS, CP
      and LS, respectively, and 94% of the samples were positive by at least one ELISA
      test. Three dogs that were negative by agglutination (2ME-RSAT) had a positive
      result by at least one ELISA, and this discrepancy was attributed to the lower
      analytical sensitivity of agglutination tests. This hypothesis was confirmed by a
      serological follow-up of seven dogs recently infected with B. canis in three of
      which the illness was diagnosed earlier by one or more ELISA tests than by 2ME
      RSAT. Among dogs having pathological conditions other than brucellosis,
      specificities were 94.3, 96.7 and 96.7% for the ELISAs with HS, CP and LS,
      respectively. This study shows that HS-ELISA and CP-ELISA are highly specific and
      sensitive for the diagnosis of canine brucellosis and can detect the infection by
      B. canis shortly after the exposure to the pathogen.

PMID- 12220812
TI  - Characterization of virulence plasmid types in Rhodococcus equi isolates from
      foals, pigs, humans and soil in Hungary.
AB  - Rhodococcus equi isolates (204) obtained from foals (lung abscesses, lymph nodes,
      nasal discharge, rectal swabs) bred in 15 studs located throughout Hungary,
      isolates from soil samples, lymph nodes of pigs and from lesions of human
      patients were examined to determine genotypic diversity of virulence-associated
      plasmids. Isolates were tested for the presence of 15-17 kDa virulence-associated
      protein antigen (VapA) and 20k Da (VapB) genes by polymerase chain reaction
      (PCR). Plasmid DNAs were isolated and analysed by digestion with restriction
      endonucleases for estimation of size and comparison of polymorphisms. Of 146
      clinical isolates from foals in 15 studs, 129 (88.3%) gave positive results for
      the VapA gene, showing a 564 bp product of the expected size in the PCR
      amplification. Of the 129 clinical isolates from foals, 123 contained an 85 kb
      type I plasmid and the remaining six contained an 87 kb type I plasmid. Of 48
      soil isolates from two horse studs, 26 (54.2%) were positive for VapA gene and
      contained an 85 kb type I plasmid. Of three pig isolates, one was positive for
      VapA gene and contained an 85 kb type I plasmid, and the remaining two were
      positive for the VapB gene, showing a 827 bp product of the expected size in the
      PCR amplification and were R. equi of intermediate virulence which contained a 95
      kb type S5 plasmid. Of the seven human isolates, five were positive for VapB gene
      by PCR, these were R. equi of intermediate virulence, which contained a 95 kb
      type S5 plasmid. These results revealed that virulent R. equi strains harbouring
      a virulence plasmid of 85 kb type I or 87 kb type I, which have been found in
      clinical isolates from Europe and North and South America, are widespread in
      Hungary. Furthermore, same intermediately virulence plasmid type was found in
      both human and pig isolates.

PMID- 12220813
TI  - Evaluation of serology, bacteriological isolation and polymerase chain reaction
      for the detection of pigs carrying Actinobacillus pleuropneumoniae in the upper
      respiratory tract after experimental infection.
AB  - Pigs, asymptomatically infected with Actinobacillus pleuropneumoniae in their
      upper respiratory tract, can transmit the infection. Detection of such animals is
      indispensable to prevent the intake of the disease in a herd. This study was
      conducted to evaluate bacteriology, polymerase chain reaction (PCR) and serology
      for the detection of subclinically infected pigs. Pigs were inoculated onto the
      tonsils with an A. pleuropneumoniae serotype 9 strain (n=12, group 1) or
      phosphate buffered saline solution (PBSS) (n=5, group 2). To prevent infection of
      the lungs, pigs of group 1 were treated three times with sodium ceftiofur as an
      aerosol. A third group (n=5) was inoculated intranasally with the same strain.
      All animals were euthanized 30 days post-inoculation (dpi). In pigs of group 1,
      clinical signs were not observed. A small lung lesion was found in only one pig
      and A. pleuropneumoniae was isolated from this lesion. The bacterium was not
      isolated from the lungs of animals that did not develop lung lesions. A.
      pleuropneumoniae was demonstrated in tonsils of 9/12 animals using
      bacteriological isolation, whereas it was demonstrated in mixed bacterial
      cultures from tonsils of all 12 animals by PCR. In non-infected animals (group
      2), clinical signs were not observed and A. pleuropneumoniae was not demonstrated
      in any sample. All intranasally infected animals (group 3) developed disease
      signs and lung lesions. High antibody titers against ApxI, ApxII and heat-stable
      antigens were detected in animals that developed lung lesions. Antibody titers
      against these antigens were low or absent in all other pigs. It was concluded
      that pigs carrying A. pleuropneumoniae in the upper respiratory tract generally
      do not show measurable antibodies in serum. Therefore, sensitive methods for the
      detection of the etiological agent such as PCR are required to identify carrier
      animals, while serological methods are not suitable.

PMID- 12220814
TI  - Follicular development and steroid concentrations in cows with different levels
      of fertility raised under nutritional stress.
AB  - The aim of the present study was to characterize ovarian follicular development
      and steroid concentrations during postpartum and the estrous cycle of Brangus
      Ibage cows (3/8 Nelore + 5/8 Aberdeen Angus) with different levels of fertility.
      Cows were classified as having high or low fertility according to the calving
      interval (CI). The average CI of the herd from which cows used in this study were
      selected was 404.6+/-5.44 and 711.2+/-20.89 days for the high and low fertility
      groups, respectively. Four cows of high fertility and five cows of low fertility
      had calves removed between 70 and 100 days after parturition. Ovarian activity
      was monitored daily by ultrasound for 16 days after calf removal. Days to
      emergency of the first follicular wave after calf removal, number of follicles
      with diameter >9 mm, growth rate of largest follicle, maximum diameter of largest
      follicle, length (days) and number of follicular waves were recorded. During this
      period, blood was collected daily for measurements of serum progesterone (P(4))
      and estradiol (E(2)) concentrations. In another experiment, ovarian activity and
      P(4) and E(2) concentrations were examined during estrous cycle in five cows of
      high fertility and four cows of low fertility. Ovarian activity and steroid
      concentrations were assessed from the day prior to estrus to the 15th day of the
      estrous cycle (estrus = day 0). In postpartum cows of high fertility, the total
      number of follicles >5mm and the maximum diameter of the largest follicle were
      higher than in cows of low fertility (P < 0.05). Concentrations of P(4) and E(2)
      did not differ between groups in the postpartum cows. However, E(2) increased 5
      days after calf removal (around 90 days of postpartum) in the high fertility
      group, followed by an increase in P(4) with average values indicating ovulation
      around 100 days postpartum. In cycling cows, the profile of follicular
      development was similar between cows of high and low fertility. There was no
      difference between groups for number of follicles >5mm, but the day effect was
      significant (P < 0.01). Plasma concentrations of P(4) and E(2) were similar in
      both groups. These data suggest that cows, from a population raised in the same
      environment have different fertility as a consequence of individual physiological
      characteristics.

PMID- 12220815
TI  - Vitrification of in vitro produced bovine embryos: in vitro and in vivo
      evaluations.
AB  - The efficacy of different vitrification solutions to cryopreserve in vitro
      produced bovine blastocysts was evaluated based upon in vitro development of
      embryos in culture and on in vivo development of embryos transferred into
      recipients. In the first experiment, ethylene glycol + glycerol (Eg + Gly) +
      different sucrose concentrations were evaluated. There were no significant
      differences in development rates among solutions. As for hatching, the Eg + Gly +
      0.1 M sucrose group had a greater rate as compared with Eg + Gly + 0 M sucrose
      and Eg + Gly + 0.5 M sucrose groups in the evaluations of Day 6, Day 7 and Day 6
      + Day 7 embryos; and, Eg + Gly + 0.3 M sucrose group had a greater rate as
      compared with the Eg + Gly + 0 M sucrose and Eg + Gly + 0.5 M sucrose groups in
      evaluations of Day 6 and Day 6 + Day 7 embryos. There were no significant
      differences in development and hatching rates between Day 6 and 7 in in vitro
      produced bovine embryos within each treatment group. There were significant
      differences in nuclei number after vitrification between Eg + Gly + 0.1 M and Eg
      + Gly + 0 M sucrose groups and the Eg + Gly + 0.5 M sucrose group. Pregnancy
      after 60 days of transfer and calving rates showed a difference between in vivo
      produced embryos freshly transferred and in vitro produced embryos vitrified with
      Eg + Gly + 0.3 M. There were no significant differences in gestation length and
      sex ratio between treatments. As for birth weight, there were significant
      differences between fresh in vivo produced embryos and all treatments of in vitro
      produced embryos. There were significant differences in dystocial parturition
      between in vivo produced embryos and all treatments with in vitro produced
      embryos. These results demonstrate that vitrification can be used successfully in
      the cryopreservation of in vitro produced bovine embryos, and that it might be
      considered for use in commercial programs.

PMID- 12220816
TI  - Efficacy of PGF(2alpha) to synchronize estrus in water buffalo cows (Bubalus
      bubalis) is dependent upon plasma progesterone concentration, corpus luteum size
      and ovarian follicular status before treatment.
AB  - This study was conducted to identify factors affecting PGF(2alpha) efficacy to
      synchronize estrus in water buffalo cows. After detection of a corpus luteum (CL)
      by rectal palpation, cows were treated (im) with dinoprost (12.5, 25 or 50mg) or
      D(+) cloprostenol (75, 150 or 300 microg) in a total of 66 treatments. Blood
      samples were collected 0, 24 and 48 h after treatment and ultrasound examinations
      and observations for estrus were performed daily to the day of ovulation or to 6
      days after treatment. No PGF(2alpha) dose-response pattern was observed and
      overall rates of luteal regression (progesterone <1.0 ng/ml at 48 h), estrus, no
      detected behavioral estrus with ovulation occurring, and ovulation were 71.2,
      36.4, 19.7 and 54.5%, respectively. To analyze plasma progesterone concentrations
      and ovarian dynamics, cows were divided in three groups according to their
      response to treatment. Cows that failed to have ovulations from a follicle after
      treatment (Group A, n = 30) had (P < 0.05) a lower plasma progesterone
      concentration (2.98 ng/ml) and smaller CL area (CLA; 187.3 mm(2)) before
      treatment as compared with cows that had an ovulation from a follicle (4.43 ng/ml
      and 223.7 mm(2), respectively; Groups B and C, n = 36). In cows that failed to
      ovulate, plasma progesterone concentration decreased in the first 24 h, but did
      not decline further and was >1.0 ng/ml 48 h after treatment. Moreover, no
      significant change in CLA after treatment was detected, indicating that treatment
      induced only partial luteolysis. In cows that ovulated, plasma progesterone
      concentration and CLA decreased continuously from treatment to ovulation
      (consistent with complete luteolysis). Threshold values of 2.8 ng/ml for plasma
      progesterone concentration and 189 mm(2) for CLA were identified as the best
      predictors of ovulation before treatment (83.3 and 80.6% sensitivity and 58.6 and
      65.5% specificity, respectively, with positive and negative predictive values
      around 71%). When the origin of the ovulatory follicle was investigated, the
      interval from treatment to ovulation was shorter (91.9 versus 113.3 h; P < 0.05),
      and the ovulatory follicle had a slower growth rate (1.02 versus 1.55 mm per day;
      P < 0.005), a lesser increase in diameter from treatment to ovulation (4.7 versus
      8.0 mm; P < 0.001), and a greater maximum diameter (13.2 versus 12.1 mm; P <
      0.05) in cows that ovulated from the largest follicle present in the ovary before
      treatment (Group B, n = 27) compared with cows that ovulated from the second
      largest follicle present in the ovary before treatment (Group C, n = 9). In
      summary, the efficacy of PGF(2alpha) for causing luteolysis and synchronizing
      estrus and ovulation in buffalo cows was dependent upon plasma progesterone
      concentration, CL size and ovarian follicular status before treatment.

PMID- 12220817
TI  - Effectiveness of an antagonist to gonadotrophin releasing hormone on the FSH and
      LH response to GnRH in perifused equine pituitary cells, and in seasonally
      acyclic mares.
AB  - We wish to use a gonadotrophin-releasing hormone (GnRH) antagonist in the mare as
      a tool for investigating the control of the oestrous cycle. The aim of this study
      was to test the effectiveness of the antagonist cetrorelix by testing both in
      vitro, using perifused equine anterior pituitary cells, and in vivo in seasonally
      acyclic mares. Pituitary cells were prepared and after 3-4 days incubation,
      loaded onto columns and given four pulses of GnRH (at 0, 30, 60 and 90 min; dose
      response study). After the second GnRH pulse, infusion of cetrorelix began (0,
      100, 1000 and 2000 pmol/l) and continued until the end of the experiment. To
      mimic luteal phase conditions, cells were pre-incubated and perifused with
      progesterone (25 nmol/l) and GnRH pulses given at 0, 90, 180 and 270 min.
      Cetrorelix (0 or 1000 pmol/l) began after the second GnRH pulse. Follicle
      stimulating hormone (FSH) and luteinizing hormone (LH) concentrations were
      measured in 5 min fractions. Both FSH and LH response areas (above baseline)
      after GnRH were inhibited by 1000 pmol/l cetrorelix (P < 0.01, P < 0.01,
      respectively) but not by 100 pmol/l cetrorelix. Similarly, in the presence of
      progesterone, cetrorelix inhibited the FSH (P < 0.001) and LH (P = 0.0002)
      response area. Seasonally acyclic mares, pre-treated for 3 days with progesterone
      (150 mg i.m. per day) were given cetrorelix as (i) a loading dose of 1 microg/kg
      then infusion at 2.2 ng/(kg min) for 90 min, (ii) a s.c. injection at 20
      microg/kg, (iii) infusion at 2.2 ng/(kg min) for 48 h, and (iv) no cetrorelix
      (control mares). At 90 min, 6, 24 and 48 h after cetrorelix was first
      administered, mares were given a bolus injection of GnRH (22.2 ng/kg i.v.) and
      the FSH and LH responses measured. All doses of cetrorelix inhibited the FSH
      response at 90 min. The response was no longer suppressed at 6 h in the 90 min
      infusion group, showing a rapid recovery from inhibition. At 24 h, the FSH
      responses in the injected and 48 h infusion group were suppressed. The LH
      concentrations were low and showed no significant changes. This study has defined
      the time course and dose of cetrorelix with respect to its effect on FSH in the
      horse. It is concluded that cetrorelix could be used to elucidate the role of FSH
      in follicular development in cyclic mares.

PMID- 12220818
TI  - Comparison of semen characteristics, sperm freezability and testosterone
      concentration between Duroc and Yorkshire boars during seasons.
AB  - This study was carried out to investigate the effects of Duroc and Yorkshire
      boars and seasons influencing semen characteristics, frozen-thawed sperm
      viability and serum testosterone concentration. Yorkshire boars produced higher
      semen volume compared to Duroc boars among seasons. However, sperm concentration
      did not differ significantly between Duroc and Yorkshire boars among seasons.
      Sperm motility of frozen-thawed sperm in Yorkshire boars was higher than in Duroc
      boars in spring and summer. Normal acrosome of frozen-thawed sperm in Yorkshire
      boars was higher than in Duroc boars in winter. Serum testosterone concentrations
      in Duroc and Yorkshire boars were higher in spring than in summer, autumn and
      winter. Serum testosterone concentrations in spring and summer were higher in
      Yorkshire boars than in Duroc boars. In conclusion, when serum testosterone
      concentrations were higher in Duroc and Yorkshire boars among seasons, semen
      volume, sperm concentration and frozen-thawed sperm viability were higher.

PMID- 12220819
TI  - Effects of sympathetic denervation on follicular distribution, oestradiol and
      progesterone serum levels in prepubertal hemi-ovariectomized female guinea pig.
AB  - Hemi-gonadectomy performed in prepubertal female guinea pigs is followed by a
      compensatory ovarian hypertrophy (COH) and compensatory ovulation (CO).
      Sympathetic denervation diminished the COH (left ovary: 28 +/- 1.6% versus 46 +/-
      4% (control), P < 0.05; and right ovary: 21.3 +/- 3.2% versus 34.2 +/- 3.7%
      (control), P < 0.01) and does not modify the CO. The mean follicular diameter
      increased only in the right ovary of hemi-gonadectomized animals. This increase
      is greater in the hemi-gonadectomized-denervated groups. The mean follicular
      diameter measured in the right and left ovaries showed an opposite response in
      hemi-ovariectomized and hemi-ovariectomized-denervated animals: the diameter
      increased in the right ovary without modifications in the left. Present results
      add further support to the participation of ovarian innervation on the
      mechanisms, which regulate follicular development.

PMID- 12220820
TI  - The stage-dependent inhibitory effect of porcine follicular cells on the
      development of preantral follicles.
AB  - The objective of this study was to examine the effects of follicular cells on the
      in vitro development of porcine preantral follicles. In Experiment 1, one
      preantral follicle alone (Trt 1) was cocultured with a follicle of the same size
      with oocytes (Trt 2) or without oocytes (Trt 3). Preantral follicles cultured
      alone in vitro for 12 days had greater follicle diameters (1017 +/- 96 microm
      versus 706 +/- 69 or 793 +/- 72 microm, P < 0.05), growth rates (201 +/- 0.3
      versus 103 +/- 0.2 or 128 +/- 0.2, P < 0.05) and oocyte survival rates (73%
      versus 48, or 25%, P < 0.05) than other groups. The inhibitory effects of
      follicle cells on the growth of preantral follicles and oocyte survival rates
      were not enhanced by the addition of oocytectomized preantral follicles
      (Experiment 2). Follicles were cocultured with different sources of follicular
      cells in other experiments. Coculture with cumulus cells enhanced oocyte survival
      compared to the control (without coculture) and mural follicular cell groups
      (Experiment 3). The growth and survival rates of oocytes collected from the group
      of follicles cocultured with cumulus cells from large antral follicles (>3 mm)
      were greater (P < 0.05) than those from small antral follicles (<3 mm), or than
      the control group (without cumulus cells, experiment 4). No significant
      differences in the follicular diameters (674 +/- 30 microm versus 638 +/- 33 and
      655 +/- 28 microm) and growth rate (105% versus 94 and 105%) were observed among
      the preantral follicles of the different treatments (P > 0.05). Taken together,
      coculture with the cells from large antral follicles (>3 mm) exerted a
      significant positive effect on oocyte survival. The growth and oocyte survival of
      preantral follicle cocultured with the same size of follicles (with or without
      oocyte) were inhibited. Growth and survival rates of preantral follicles and
      oocytes are improved by coculturing them with the cumulus cells derived from
      larger antral follicles.

PMID- 12220821
TI  - Corrigendum to "The sow endometrium at different stages of the oestrus cycle:
      studies on morphological changes and infiltration by cells of the immune system."
      [Anim. Reprod. Sci. 65 (2001) 95-114].
AB  - The aim of this study was to investigate the distribution of leukocytes and the
      morphological changes of the sow endometrium throughout the oestrous cycle.
      Fifteen crossbred multiparous sows (Swedish Landrace x Swedish Yorkshire), with
      an average parity number of 3.4+/-0.7 (mean+/-S.D.) were used. Blood samples were
      collected from the jugular vein 1 h before slaughter for analyses of oestradiol
      17beta and progesterone levels. Uterine samples from the mesometrial side of both
      horns, taken immediately after slaughter at late dioestrus, prooestrus, oestrus,
      early dioestrus and dioestrus, were fixed, embedded in plastic resin and stained
      with toluidine blue. The surface and glandular epithelium as well as
      subepithelial and glandular connective tissue layers were examined by light
      microscopy (LM). The significantly highest surface and the glandular epithelium
      were observed at oestrus and dioestrus, respectively. The largest number of
      capillaries (underneath the surface epithelium) was found at oestrus. In the
      surface epithelium, the largest number of intraepithelial lymphocytes (IELs,
      round nucleus) was found at early dioestrus. The largest number of lymphocytes
      and macrophages within the glandular epithelium were found at early dioestrus and
      oestrus, respectively. In the subepithelial connective tissue layer, the most
      common type of leukocytes during all stages was the lymphocyte. The largest
      numbers of lymphocytes and neutrophils were found at oestrus while the largest
      number of eosinophils was found at dioestrus. The dominating cells of the immune
      system in the connective tissue of the glandular layer were lymphocytes and
      macrophages. The significantly largest numbers of lymphocytes and plasma cells
      were found at early dioestrus and dioestrus, respectively. The number of
      lymphocytes in the connective tissue of the glandular layer and the number of
      plasma cells in the subepithelial layer were positively correlated with the
      plasma level of progesterone (P < or = 0.05). The numbers of capillaries and
      neutrophils in the subepithelial layer underneath the surface epithelium as well
      as the number of macrophages in both surface and glandular epithelium were
      positively correlated with the plasma level of oestradiol-17beta (P < or = 0.05).
      In conclusion, the present study showed a variation om the infiltration and
      distrobution of lymphocytes, neutrophils, eosinophils, macrophages, mast cells,
      and plasma cells in the sow endometrium during different stages of the oestrous
      cycle. Also morphological parameters (e.g. height of surface and glandular
      epithelium, capillaries density and degree of oedema) varied throughout the
      oestrous cycle.

PMID- 12220822
TI  - Corrigendum to "The sow endometrium at different stages of the oestrous cycle:
      studies on the distribution of CD2, CD4, CD8 and MHC class II expressing" cells.
      [Anim. Reprod. Sci. 68 (2001) 99-109].
AB  - The aim of this study was to investigate the distribution of CD2(+), CD4(+),
      CD8(+) lymphocyte subpopulations and MHC class II expressing cells in the sow
      endometrium throughout the oestrous cycle. Fifteen crossbred multiparous sows
      (Swedish Landrace x Swedish Yorkshire), with an average parity number of 3.4 +/-
      0.7 (mean +/- S.D.) were used. Uterine samples from the mesometrial side of both
      horns, taken immediately after slaughter at late dioestrus (day 17, n = 3),
      prooestrus (day 19, n = 3), oestrus (day 1, n = 3), early dioestrus (day 4, n =
      3) and dioestrus (days 11-12, n = 3), were stored in a freezer at -70 degrees C
      until analysed by immunohistochemistry with an avidin-biotin peroxidase method
      using monoclonal antibodies to lymphocyte subpopulations and MHC class II
      molecules. The surface and glandular epithelium as well as connective tissue
      layers in subepithelial and glandular areas were examined by light microscopy.
      For the T lymphocyte subpopulations, all oestrous cycle stages and different
      tissue layers taken together, the most commonly observed cell type was CD2(+)
      cells. The largest number of CD2(+) cells within the surface and glandular
      epithelium were observed at oestrus and early dioestrus. In the surface
      epithelium, a larger number of CD8(+) cells compared with CD4(+) cells were
      observed and no CD4(+) cells were found within the glandular epithelium at any
      stage of the oestrous cycle. In the subepithelial and glandular connective tissue
      layers, during the oestrus cycle stages, a larger number of CD4(+) cells compared
      with CD8(+) cells were found. Endothelial cells in the connective tissue
      generally expressed MHC class II. However, no obvious differences between
      oestrous cycle stages were observed. For other cells than endothelial cells, the
      result was as follows. In the surface epithelium, a large number of MHC class II
      expressing cells was observed at oestrus compared with the other stages. No MHC
      class II expressing cells were found at late dioestrus and dioestrus. MHC class
      II expressing cells were also found in the glandular epithelium, and in the
      subepithelial and glandular connective tissue layers during all oestrous cycle
      stages but with no significant differences between stages. In conclusion, the
      present study showed a variation in the distribution of T lymphocyte
      subpopulations (CD2(+), CD4(+) and CD8(+)) and MHC class II expressing cells in
      the sow endometrium during different stages of the oestrous cycle. Also a
      variation between different tissue layers was found. It is suggested that helper
      and cytotoxic function of the immune system have primary locations in different
      tissue layers of the endometrium.

PMID- 12220823
TI  - Successful transfer of vitrified Ilama (Lama glama) embryos.
AB  - The exploitation of the domestic animals species of South American camelids is of
      great social importance for the native people living in the High Andes. The
      reproductive physiology of these species is a unique challenge in the development
      of advanced breeding techniques. At present, the cryopreservation of embryos has
      not been developed and very few investigations have been conducted. The objective
      of the present work was to evaluate the in vivo survival of vitrified llama
      embryos after transfer to recipient females. Donors females were treated with a
      CIDR-estradiol benzoate-eCG regimen and were mated naturally 6 days after CIDR
      withdrawal. One ovulatory dose (8 microg) of GnRH was administered immediately
      after mating. A second mating was allowed 24 h later. Embryo recovery was
      performed nonsurgically between 8 and 8.5 days after the first mating. Twenty-two
      ova/embryos were recovered from 12 donor females. Hatched blastocysts were
      exposed to vitrification solution (20% glycerol + 20% ethylene glycol + 0.3 M
      sucrose + 0.375 M glucose + 3% polyethylene glycol (P/V)) in three steps, and
      after loading into 0.25 ml straws, were plunged into liquid nitrogen. For embryo
      transfer, recipients animals were ovulation-synchronized using GnRH administered
      at the same time as donors. A total of eight vitrified-warmed embryos and 12
      fresh embryos were nonsurgically transferred to four and six recipient females,
      respectively (two embryo per recipient). The pregnancy rates were 50 and 33.3%
      for recipients that had received vitrified embryos and fresh embryos,
      respectively. The results demonstrated the effectiveness of this simple
      vitrification method for cryopreservation of llama embryos.

PMID- 12220824
TI  - Estimation of the critical rate of temperature rise for thermal explosion of
      first-order autocatalytic decomposition reaction systems using non-isothermal
      DSC.
AB  - A method of estimating the critical rate of temperature rise for thermal
      explosion of first-order autocatalytic decomposition reaction systems using non
      isothermal DSC is presented. Information is obtained on the increasing rate of
      temperature in highly nitrated nitrocellulose containing 14.14% of nitrogen when
      the first-order autocatalytic decomposition converts into thermal explosion.

PMID- 12220825
TI  - Waste plastics as supplemental fuel in the blast furnace process: improving
      combustion efficiencies.
AB  - The possibility of using waste plastics as a source of secondary fuel in a blast
      furnace has been of recent interest. The success of this process, however, will
      be critically dependent upon the optimization of operating systems. For instance,
      the supply of waste plastics must be reliable as well as economically attractive
      compared with conventional secondary fuels such as heavy oil, natural gas and
      pulverized coal. In this work, we put special importance on the improvement of
      the combustibility of waste plastics as a way to enhance energy efficiency in a
      blast furnace. As experimental variables to approach this target, the effects of
      plastic particle size, blast temperature, and the level of oxygen enrichment were
      investigated using a custom-made blast model designed to simulate a real furnace.
      Lastly, the combustion efficiency of the mixture of waste plastics and pulverized
      coal was tested. The observations made from these experiments led us to the
      conclusion that with the increase of both blast temperature and the level of
      oxygen enrichment, and with a decrease in particle size, the combustibility of
      waste polyethylene could be improved at a given distance from the tuyere. Also it
      was found that the efficiency of coal combustion decreased with the addition of
      plastics; however, the combustion efficiency of mixture could be comparable at a
      longer distance from the tuyere.

PMID- 12220826
TI  - Effect of humic substances on Cu(II) solubility in kaolin-sand soil.
AB  - The type and amount of organic matter present in industrially contaminated soils
      will influence the risk they pose. Previous studies have shown the importance of
      humic and fulvic acids (FAs) (important components of soil organic matter) in
      increasing the solubility of toxic metals but were not carried out using toxic
      metal levels and the pH range typical of industrially contaminated soils. This
      study investigated the influence of three humic substances (HSs: humates,
      fulvates and humins) on the solubility of copper(II) ions in kaolinitic soil
      spiked with Cu at levels representative of industrially contaminated soil.
      Humates, fulvates and humin were extracted from Irish moss peat, and controlled
      pH batch leaching tests were conducted on an artificial kaolin-sand soil that was
      spiked with each. Further leaching tests were conducted on soil spiked with each
      HS and copper nitrate. Dissolved organic contents were determined by titration
      and total and free aqueous copper concentrations in the leachate were measured
      using AAS and ion selective electrode (ISE) potentiometry respectively (dissolved
      complexed copper levels were determined by difference). It was found that humates
      and fulvates are partially sorbed by the soil, probably by chemisorption on
      positively charged gibbsite (Al-hydroxide) sites in the kaolinite. The addition
      of 340 mg/kg Cu(II) ions did not significantly affect the amount of humate or
      fulvate sorbed. Dissolved humates and fulvates form soluble complexes with copper
      over the pH range 3-11. However, in the presence of kaolinite, soluble copper
      humates and fulvates are unable to compete with the kaolinite for Cu ions at pH 6
      7. Above pH 8, humate and fulvate complexes are the only forms of dissolved Cu.
      Humin is largely insoluble and has little effect on Cu mobility between pH 2 and
      12. The implication of this study is that measurement of total soil organic
      content and water leaching tests should be a standard part of contaminated site
      investigation.

PMID- 12220827
TI  - Electrochemical generation of aluminum sorbent for fluoride adsorption.
AB  - Aluminum sorbent (Al-sorbent) was produced in a parallel-plate electrochemical
      reactor by anodic dissolution of aluminum electrodes in a dilute sodium chloride
      (NaCl) aqueous solution. The NaCl in the solution effectively reduced the power
      consumption and promoted the sorbent generation by depasivating the aluminum
      water electrochemical system. The freshly generated Al-sorbent was able to reduce
      fluoride concentration from 16 to 2 mg/l in 2 min. The final concentration was
      further reduced to 0.1 mg/l by partial neutralization of the mixture to pH 6.3.
      The sorbent generation and fluoride adsorption was integrated into a single
      electrochemical reactor. The system was able to reduce the fluoride concentration
      from 16 to 6 mg/l in 2 min of treatment and to about 2 mg/l in 4 min. The
      effluent from the electrochemical system needs pH adjustment to bring the
      fluoride concentration down to less than 1 mg/l.

PMID- 12220828
TI  - Feasibility of metal recovery from soil using DTPA and its biostability.
AB  - Removal of heavy metals from contaminated soil by chelation can be a valid
      remediation method. Important properties of the chelating agent used are:
      strength of the chelation bonding, reusability, and biostability during the
      remediation operation. This work tested the extraction, recovery, and
      biostability of diethylenetriaminepentaacetate (DTPA) as a remediation agent for
      soils contaminated with metals. Reported here are effects of parameters such as
      DTPA concentration, precipitant type and concentration, and pH relative to
      extraction and recovery efficiencies of the chelator, as well as workable
      recovery conditions. The assessment of biostability was determined at different
      DTPA concentrations, in aqueous and soil slurry systems, and in presence of lead
      using acclimated and unacclimated activated sludge cultures. The results showed
      that DTPA was capable of extracting lead from the tested contaminated soils and
      could be recovered by the use of cationic and anionic precipitants in alkaline pH
      conditions. It was biostable to some extent especially with unacclimated
      cultures. Thus, DTPA proved to be a strong and reusable chelating agent for some
      metals in soils, and it was relatively biostable, which makes it a valid
      remediation agent for soil metal extraction.

PMID- 12220829
TI  - Thermal treatment of soils contaminated with gas oil: influence of soil
      composition and treatment temperature.
AB  - Samples of two soils containing different organic matter contents, neat or
      contaminated with gas oil (diesel fuel oil) at 2.5 wt.% were heated from room
      temperature to different final temperatures (200-900 degrees C). The experiments,
      performed in an anaerobic media, simulate conditions pertinent to ex situ thermal
      desorptive and thermal destructive treatments. The products generated during the
      heating were collected and light gases were analyzed by gas chromatography. The
      results indicate that the chemical composition of the soil is a key factor since
      it strongly influences the quantity and composition of the off-gases. According
      to the liquid and light gas yields, the gas oil does not affect appreciably the
      generation of pyrolysis products of the own soil constituents and the gas oil
      does not suffer significant chemical transformations even at high operating
      temperatures (e.g. 900 degrees C). With surface areas of 16000 cm(2)/g (Soil A)
      and 85000 cm(2)/g (Soil B) based on the monolayer adsorbed model, 4 and 20%,
      respectively, of the original gas oil can be adsorbed. These values are in good
      agreement with experimental data. Even for high temperatures, the employed
      thermal treatment is capable to practically remove the gas oil from the soil bed
      without changing appreciably the original chemical composition of the
      contaminant.

PMID- 12220830
TI  - Adsorption of cadmium from aqueous solutions by perlite.
AB  - The present study examined the use of perlite for the removal of cadmium from
      aqueous solutions. The effects of pH and contact time on the adsorption process
      were examined. The optimum pH for adsorption was found to be 6.0. Residual
      cadmium concentration reached equilibrium in 6h and the rate of cadmium
      adsorption by perlite was rapid in the first hour of the reaction time. Ho's
      pseudo-second-order model best described the kinetics of the reaction. Batch
      adsorption experiments conducted at room temperature (22+/-1 degrees C) showed
      that the adsorption pattern followed the Freundlich isotherm model. The maximum
      removal of cadmium obtained from batch studies was 55%. Thomas model was used to
      describe the adsorption data from column studies. The results generally showed
      that perlite could be considered as a potential adsorbent for cadmium removal
      from aqueous solutions.

PMID- 12220833
TI  - Chitosan and its derivatives--a promising non-viral vector for gene transfection.
AB  - The ability of a vector to ferry gene into targeted cells is the premise of
      improving gene-transfer efficiency. Chitosan, a naturally occurring cationic
      polysaccharide, has been shown to excel in transcellular transport. This
      attribute has been fully reflected in chitosan-mediated gene transfection
      systems. The objective of this review is to summarize the recent encouraging
      advances in unveiling the mechanism of cell entry and application of chitosan and
      its derivatives as novel non-viral vectors. It is our belief that researchers
      will uncover more truth about chitosan-based vector and realize the long-term
      goal of gene transfection--produce the desired clinical effect.

PMID- 12220834
TI  - Sonicated transdermal drug transport.
AB  - The following review explores the promise shown by sonicated transdermal drug
      transport as a novel drug delivery system in great detail. It elucidates the
      advantages of transdermal drug transport (TDT) over the currently prevalent modes
      of drug administration and then goes on to explain why despite these obvious
      advantages TDT is so sparingly used. This discussion includes the problems posed
      by the impregnable barrier--our skin, or more precisely the stratum corneum (SC),
      and how sonicated TDT breaches this barrier. A succinct definition of
      sonophoresis is included along with a description of the experimental setup and a
      discussion of the results. The mechanism of sonophoresis with particular emphasis
      on the role of cavitation (both inside and outside the skin), thermal effects,
      convective transport, and mechanical stresses is also included. The paper also
      includes a discussion on the variation of sonophoretic enhancement from drug to
      drug along with a recent mathematical model explaining this. The paper concludes
      with a section detailing possible applications of sonicated TDT in the near
      future.

PMID- 12220835
TI  - Water flea Moina macrocopa as a novel biocarrier of norfloxacin in aquaculture.
AB  - The potential of using water flea Moina macrocopa as a novel live drug carrier to
      freshwater aquatic animals has been evaluated. The incorporation of
      antibacterial, norfloxacin into Moina and subsequently into fish was quantified.
      The efficiency of drug incorporation into water flea depends on both drug
      concentration in enrichment medium and incubation time. The maximum drug level in
      Moina following bioencapsulation technique was reached at 4 h of exposure at drug
      concentrations of 10-20% (w/w) (0.70-0.90 mg/g dry weight of water flea).
      Significant higher drug uptake was obtained (1.902+/-0.228 mg/g dry weight of
      water flea) in 2 h at the drug concentration of 40%. A marked decrease of
      norfloxacin percentage level upon storage of the Moina in water was observed and
      the survival of the Moina up to 2 h was satisfactory. It was suggested that
      medicated water flea should be either administered freshly enriched to fish or
      after short duration of storage. Following oral administration of medicated water
      flea to fish, the level of drug in fish body tissue increased as the number of
      doses increased, and the drug level was highest after a three-dose feeding. This
      primary food source appears to be a promising drug delivery system to aquatic
      animals.

PMID- 12220836
TI  - FTIR imaging for the characterization of controlled-release drug delivery
      applications.
AB  - The diffusion of nicotine in ethanol/water mixtures into an ethylene-vinyl
      acetate (EVA) copolymer membrane was studied by FTIR imaging. The spatial and
      temporal distribution of each component in the EVA membrane was demonstrated in
      the FTIR images. The concentration profiles extracted from these images showed
      that segregation occurs during diffusion. Nicotine diffuses into EVA ahead of the
      solvent for 0-60 wt% ethanol/water mixtures, but the segregation behavior changes
      as the ethanol in the solvent increases to 80 wt%; for the 80 wt% ethanol
      solvent, D(2)O leads the diffusion front, and for the 100% ethanol solvent,
      ethanol diffuses into EVA first. The initial swelling rates were calculated from
      the concentration profiles, and an exponential trend with increasing ethanol in
      the solvent was observed. The concentration profiles were also used to calculate
      average diffusion coefficients for the overall solutions and specifically for
      nicotine. The relative intensities of the aromatic ring stretching bands of
      nicotine in solution indicate that the solvation properties in pure ethanol and
      water are not equivalent; a pseudo-conjugation scheme between water and nicotine
      was proposed to account for this difference. Examination of the intensity of the
      carbonyl band of the EVA film revealed an interaction with the solvents by
      hydrogen bonding.

PMID- 12220837
TI  - Associative pullulan gels and their interaction with biological active
      substances.
AB  - This paper studies the synthesis and properties of anionic and/or amphiphilic
      pullulan microparticles crosslinked with epichlorohydrine or with sodium
      trimethaphosphate. The polysaccharide gels were physicochemically characterized
      and their interaction with enzymes (lysozyme) was studied with the aim to
      appreciate the performances for separation/purification/immobilization of the
      enzymes or controlled release drug systems.

PMID- 12220838
TI  - Delivery of osteoinductive growth factors from degradable PEG hydrogels
      influences osteoblast differentiation and mineralization.
AB  - Degradable poly(ethylene glycol) (PEG) hydrogels with varying mass loss profiles
      were investigated to assess their applicability as delivery vehicles for
      osteoinductive growth factors in bone tissue engineering. Protein release is
      readily controlled by changes in both the structure (i.e., macromer
      concentration) and chemistry (i.e., number of degradable units) of the starting
      macromer. In vitro studies indicate an increase in total protein levels, alkaline
      phosphatase, and mineralization by osteoblasts cultured in the presence of
      osteoinductive growth factors compared to cells cultured with standard media.
      When growth factors are delivered from a 25 wt% hydrogel, a significant increase
      in both alkaline phosphatase and mineralization was seen after 3 weeks of culture
      over growth factor delivery in a bolus fashion. Additionally, gene expression
      levels of both osteocalcin and type I collagen were higher at early timepoints
      when growth factors were released from hydrogels. These results indicate that
      growth factors remain active after photoencapsulation, that the sustained
      delivery of growth factors alters various markers of osteoblastic
      differentiation, and that these networks could be useful as delivery vehicles for
      growth factors in bone tissue engineering. Finally, ectopic bone formation was
      present in subcutaneous rat tissue after implantation of hydrogel networks loaded
      with osteoinductive growth factors.

PMID- 12220839
TI  - Thermosetting gels with modulated gelation temperature for ophthalmic use: the
      rheological and gamma scintigraphic studies.
AB  - For ophthalmic drug delivery, Pluronic F127 solutions have a phase transition
      temperature too low for them to be instilled into the eye at room temperature.
      Refrigerator storage is usually required to make administration easier, whereas
      the potential irritation of cold to the sensitive ocular tissues may result in
      poor topical bioavailability. The purpose of this study is to develop a
      thermosetting gel with a suitable phase transition temperature by combining
      Pluronic analogs and to examine the influence of incorporating mucoadhesive
      polysaccharide, sodium hyaluronate (HA-Na), on the ocular retention of the gel.
      Dynamic rheological method and single photon emission computing tomography
      (SPECT) technique were used to ex/in vivo evaluate the thermosetting gels,
      respectively. An optimized formulation containing 21% F127 and 10% F68 increased
      the phase transition temperature by 9 degrees C as evaluated by elasticity
      modulus compared to that of individual 21% F127 solution. Rheological behaviors
      of the Pluronic solutions showed that the combined Pluronic formulation was free
      flowing liquid below 25 degrees C and converted to a firm gel under the
      physiological condition. Furthermore, this formulation possessed the highest
      viscosity both before and after tear dilution at 35 degrees C. Gamma
      scintigraphic data demonstrated that the clearance of the thermosetting gel
      labeled with 99mTc-DTPA was significantly delayed with respect to the phosphate
      buffered solution, and at least a threefold increase of the corneal residence
      time was achieved. However, no further improvement in the ocular retention was
      observed when adding HA-Na into the thermosetting gel due to the substantially
      decreased gel strength.

PMID- 12220840
TI  - Liver targeting of human interferon-beta with pullulan based on metal
      coordination.
AB  - Although interferon (IFN)-beta is widely used for the elimination of hepatitis C
      virus in patients with chronic liver disease, its clinical efficacy is
      unsatisfactory. Targeting IFN-beta to the liver might enhance its efficacy
      without increasing its side effects. The objective of the present study was to
      target IFN-beta to the liver to enhance its biological activity and reduce its
      side effects. A chelating residue, diethylenetriaminepentaacetic acid (DTPA), was
      introduced to pullulan, a water-soluble polysaccharide with a high affinity to
      the liver (DTPA-pullulan) and natural human IFN-beta was coordinately conjugated
      with the DTPA-pullulan by mixing in an aqueous solution containing zinc ions
      (Zn(2+)). Intravenous injection of the IFN-beta-DTPA-pullulan conjugate with
      Zn(2+) coordination into mice enhanced induction of an antiviral enzyme, 2',5'
      oligoadenylate synthetase (2-5AS), specifically in the liver to a significantly
      greater extent than free natural IFN-beta. The enhanced 2-5AS level in the liver
      depended on the molar mixing ratio of IFN-beta, DTPA residue of the DTPA
      pullulan, and Zn(2+). Moreover, the duration of the liver 2-5AS induction by the
      IFN-beta-DTPA-pullulan conjugate was longer than that by free natural IFN-beta.
      Thus, human IFN-beta-DTPA-pullulan conjugate appears to be applicable for
      clinical use, which is promising for treatment of patients with chronic hepatitis
      C.

PMID- 12220841
TI  - Important role of serum proteins associated on the surface of particles in their
      hepatic disposition.
AB  - To elucidate the important factors for the difference in the hepatic disposition
      between polystyrene nanospheres with a size of 50 nm (NS-50) and lecithin-coated
      NS-50 (LNS-50), the liver perfusion studies and the in vitro uptake studies using
      the cultured Kupffer cells were performed. It was suggested that opsonin-mediated
      phagocytosis is not significantly involved in the hepatic disposition of LNS-50
      in the presence of serum, whereas its involvement in the hepatic uptake of NS-50
      was clearly demonstrated. Western blot analysis showed that IgG, complement C3,
      and fibronectin, well-known opsonins in the serum, adsorbed on the surface of NS
      50 in larger amount than on the surface of LNS-50. On the other hand, serum
      albumin, which was suggested to function as a dysopsonin for the hepatic
      disposition of NS-50, was associated with both spheres almost to the same extent.
      These findings suggest that the hepatic disposition of LNS-50 at lower level
      should be ascribed to the less amount of serum opsonins associated on the surface
      and that the serum proteins associated with these spheres should be important as
      a determinant for their hepatic disposition.

PMID- 12220842
TI  - Poly(ethylene glycol)-avidin bioconjugates: suitable candidates for tumor
      pretargeting.
AB  - Avidin-poly(ethylene glycol) (PEG) conjugates were obtained by derivatization of
      about 10% of the protein amino groups (four amino groups per protein molecule)
      with linear 5 kDa PEG or branched 10 or 20 kDa PEGs. Circular dichroism analysis
      showed that the polymer conjugation neither altered the protein structure nor the
      environment of the aromatic amino acids which are present at the level of the
      biotin binding site. Spectroscopic studies were carried out to evaluate the
      biotin recognition activity of the conjugates either in terms of number of biotin
      binding sites or avidin/biotin affinity. Avidin-PEG 5 kDa and avidin-PEG 10 kDa
      displayed over 90% of the native protein biological activity while a reduction in
      the recognition of biotinylated antibodies of about 25% was found with PEG 20
      kDa. In vivo studies demonstrated that the protein immunogenicity was in the
      order: wild type avidin>avidin-PEG 5 kDa>avidin-PEG 10 kDa>avidin-PEG 20 kDa. By
      intravenous injection into mice bearing a solid tumor, all conjugates displayed
      prolonged permanence in the circulation with respect to the native protein. The
      area under the curve values of avidin-PEG 5 kDa, avidin-PEG 10 kDa and avidin-PEG
      20 kDa were about 3-, 7- and 30-times higher than the wild type avidin with
      reduced accumulation in kidneys and liver. Interestingly, all conjugates
      accumulated significantly in the tumor mass. In particular, in the case of avidin
      PEG 20 kDa, 8% of the injected dose (ID)/g of tissue accumulated in the tumor
      after 5 h from the administration and over 6% of the ID/g was maintained
      throughout 72 h.

PMID- 12220843
TI  - A receptor-mediated gene delivery system using streptavidin and biotin
      derivatized, pegylated epidermal growth factor.
AB  - An efficient receptor-mediated non-viral gene delivery formulation based on mono
      pegylated recombinant human epidermal growth factor (EGF) was developed using a
      streptavidin-biotin system. Biotin-derivatized and mono-pegylated EGF was
      prepared by conjugating a biotin-PEG-NHS derivative to EGF and purified through a
      chromatographic method. Luciferase plasmid DNA and polyethylenimine (PEI) were
      complexed to form positively charged nanoparticles on which negatively charged
      streptavidin was first coated and then biotin-PEG-EGF conjugate was immobilized
      via streptavidin-biotin interaction. The EGF-PEG-biotin-streptavidin-PEI-DNA
      complexes were characterized in terms of their effective diameter and surface
      zeta (zeta)-potential value under various formulation conditions. The formulated
      complexes exhibited high transfection efficiency (approximately 10(8) in
      luciferase activity) with no inter-particle aggregation. This was attributed to
      enhanced cellular uptake of the resultant complexes via receptor-mediated
      endocytosis. Furthermore, in the presence of serum proteins, a slight decrease in
      transfection efficiency was observed due to the presence of PEG chains on the
      surface.

PMID- 12220844
TI  - Characterization of a novel diolein-based LPDII vector for gene delivery.
AB  - LPDII vectors are non-viral vehicles for gene delivery comprised of polycation
      condensed plasmid DNA (polyplexes) complexed with anionic pH-sensitive liposomes.
      Here, we describe a novel LPDII formulation containing polyethylenimine (PEI)
      polyplexes complexed with anionic pH-sensitive liposomes composed of
      diolein/cholesteryl hemisuccinate (CHEMS) (6:4 mol/mol). The pH-sensitivity of
      diolein/CHEMS liposomes was evaluated through quantitative fluorescence
      measurements of calcein release and particle size analysis. The results indicated
      that diolein/CHEMS liposomes are stable at physiological pH, but undergo rapid
      aggregation and fluorescence dequenching at pH values < or =5.0. Using a
      luciferase reporter gene, in vitro transfection of KB oral cancer cells showed
      that the transfection efficiency of LPDII vectors was superior to other well
      characterized polyplexes and lipoplexes. Results further showed that gene
      delivery using diolein-containing LPDII vectors was dependent on the PEI
      nitrogen/DNA phosphate (N/P) ratio, the lipid/DNA weight ratio and the cell line
      being transfected. Replacing PEI with poly-L-lysine as the DNA condensing agent
      resulted in only a moderate reduction in transfection activity. Moreover, in
      contrast to LPDII formulations incorporating dioleoylphosphatidylethanolamine
      (DOPE), the transfection efficiency of diolein-based LPDII vectors was sustained
      in media containing up to 50% fetal bovine serum. Since diolein-based LPDII
      vectors mediate efficient gene transfer and retain their transfection activity in
      the presence of serum, diolein may be a promising alternative to DOPE for the
      construction of non-viral vectors for in vivo gene delivery.

PMID- 12220845
TI  - Targeted oligonucleotide delivery in human lymphoma cell lines using a
      polyethyleneimine based immunopolyplex.
AB  - The efficacy of antisense gene therapy depends on efficient delivery of
      oligonucleotides into targeted cells. Although polyethyleneimine based polyplexes
      have been reported as good transfection reagents, they are inefficient in
      lymphoid cell transfection. We report the construction of an immunopolyplex, a
      targeted nonviral vector based on a polyplex backbone and its application for
      oligonucleotide transfer on human lymphoma cell lines. The salient characteristic
      of immunopolyplex lies in the possibility of easily replacing the targeting
      element (antibody), leaving the polyplex backbone intact. Furthermore, a study
      was made of the influence of endocytosis inhibitors on immunopolyplex activity.
      The capacity of the immunopolyplex for oligonucleotide transfer was studied in
      vitro using FITC-labeled oligonucleotides as fluorescent reporters, an anti-CD3
      antibody as targeting element, and a CD3-positive cell line (Jurkat) as a target
      cell line, in the absence and presence of endocytosis inhibitors. A CD3-negative
      Jurkat-derived mutant cell line (J.RT3-T3.5) was used as control. A nine-fold
      increase in fluorescence in the CD3-positive above that in the CD3-negative cell
      line was observed, indicating that oligonucleotide transfer is mainly specific.
      Low fluorescence values were obtained in the presence of endocytosis inhibitor or
      with untargeted polyplexes. We conclude that the immunopolyplex is a good
      nonviral vector for specific oligonucleotide delivery. Abolition of
      immunopolyplex activity in the presence of endocytosis inhibitor suggests that
      targeted oligonucleotide transfer occurs through an endocytic pathway.

PMID- 12220846
TI  - Influences of preparation conditions on particle size and DNA-loading efficiency
      for poly(DL-lactic acid-polyethylene glycol) microspheres entrapping free DNA.
AB  - Poly-DL-lactic acid-polyethylene glycol (PELA) with different contents and
      different molecular weight of polyethylene glycol (PEG) was used as a DNA
      delivery system. DNA-loaded PELA or poly(DL-lactic acid) (PLA) microspheres were
      prepared by the emulsion evaporation technique, which was based on the water-in
      oil-in-water solvent evaporation method. The purpose of the present work was to
      investigate the factors influencing particle size and DNA loading efficiency for
      the PELA microspheres containing free DNA. During the preparation process,
      different conditions were used and the resulting microspheres were characterized
      by particle size and DNA loading efficiency. Microspheres prepared by PELA with a
      PEG (molecular weight: 6000 Da) content of 6-10% obtained the highest loading
      efficiency and smaller particle size among other PELA copolymer and PLA
      homopolymer. When the solvent of the oil phase was composed of methylene chloride
      and ethyl acetate (1:1, v/v), the highest loading efficiency and smaller particle
      size were also obtained for the PELA microspheres. The presence of the surfactant
      in oil phase influenced both the particle size and loading efficiency. Increasing
      the concentration of polymer in oil phase resulted in an increase of particle
      size and loading efficiency for DNA-loaded PELA microspheres. The addition of a
      hydrophilic polymer into the internal water phase ameliorated the DNA loading
      efficiency and reduced the particle size. Significant influences of DNA molecular
      weight and structure on the particle size and loading efficiency were observed.
      The volume and concentration of the external water phase also influenced the
      particle size and loading efficiency.

PMID- 12220847
TI  - New polyphosphoramidate with a spermidine side chain as a gene carrier.
AB  - A new cationic polymer (PPA-SP), polyphosphoramidate bearing spermidine side
      chain, was prepared as a non-viral vector for gene delivery. PPA-SP was
      synthesized from poly(1,2-propylene H-phosphonate) by the Atherton-Todd reaction.
      The weight average molecular weight of PPA-SP was 3.44x10(4) with a number
      average degree of polymerization of 90, as determined by GPC/LS/RI method. The
      average net positive charge per polymer chain was 102. PPA-SP was able to
      condense plasmid DNA efficiently and formed complexes at an N/P ratio (free amino
      groups in polymer to phosphate groups in DNA) of 2 and above, as determined by
      agarose gel electrophoresis. This new gene carrier offered significant protection
      to DNA against nuclease degradation at N/P ratios above 2, and showed lower
      cytotoxicity than PLL and PEI in cell culture. The LD(50) of PPA-SP was 85
      microg/ml in COS-7 cells, in contrast to 20 and 42 microg/ml for PLL and PEI,
      respectively. The complexes prepared in saline at N/P ratios of 5 approximately
      10 had an average size of 250 nm and zeta-potential of 26 mV. PPA-SP mediated
      efficient gene transfection in a number of cell lines, and the transfection
      protocol was optimized in HEK293 cells using a luciferase plasmid as a marker
      gene. Gene expression mediated by PPA-SP was greatly enhanced when chloroquine
      was used in conjunction at a concentration of 100 microM. Under the optimized
      condition, PPA-SP/DNA complexes yield a luciferase expression level closed to
      PEI/DNA complexes or Transfast mediated transfection. In a non-invasive CNS gene
      delivery model, PPA-SP/DNA complexes yielded comparable bcl-2 expression as
      PEI/DNA complexes in mouse brain stem following injection of the complexes in the
      tongue.

PMID- 12220848
TI  - Structure-activity relationships of poly(L-lysines): effects of pegylation and
      molecular shape on physicochemical and biological properties in gene delivery.
AB  - The influence of shape, molecular weight and pegylation of linear, grafted,
      dendritic and branched poly-L-lysines on their DNA delivery properties were
      investigated. DNA binding, condensation, complex size and morphology, cell uptake
      and transfection efficiency were determined. Most polylysines condense DNA,
      linear polymers being more efficient than most dendritic ones. At low molecular
      weights of PLL DNA binding and condensation were less efficient, particularly
      with dendrimers. Pegylation did not decrease DNA condensation of PLLs at less
      than 60% (fraction of M(w)) of PEG. Pegylation stabilized the complexes
      sterically, but did not protect them from interaction with polyanionic
      chondroitin sulfate. Cell uptake of polylysine/DNA complexes was high and
      pegylation increased the transfection efficacy. However, overall transfection
      level of polylysines is low possibly due to inadequate escape of the complexes
      from endosomes or poor release of DNA from the complexes. Physicochemical and
      biological structure-property relationships of poly-L-lysines were demonstrated,
      but no clear correlations between the tested physicochemical determinants (size
      of complexes, zeta-potentials, condensation of DNA and the shape of complexes)
      and biological activities were seen. Transfection activity may be ultimately
      determined by intracellular factors and/or still unknown features of DNA
      complexation with the carriers.

PMID- 12220849
TI  - Incorporation of lipophilic pathways into the porous pathway model for describing
      skin permeabilization during low-frequency sonophoresis.
AB  - Application of low-frequency sonophoresis (LFS) has been shown to increase skin
      permeability, thereby facilitating delivery of hydrophilic solutes. We have
      previously shown that the modified porous pathway model provides an adequate
      theoretical description of transdermal delivery of hydrophilic solutes through
      pores in the presence and absence of ultrasound. However, small hydrophilic
      solutes (M(w)<400 Da) that exhibit a moderate partition coefficient, K(o/w)
      (0.1<K(o/w)<1), may also have a substantial contribution to permeability from
      transport through intercellular lipid bilayers. The aim of this note is to
      incorporate the lipophilic pathway into the porous pathway model to describe
      transdermal drug transport in the absence and presence of ultrasound.

PMID- 12220850
TI  - Genetic tags for labelling live cells: gap junctions and beyond.
AB  - The availability of green fluorescent protein (GFP) as a tracer for observing
      proteins in living cells has revolutionized cell biology and spurred an intensive
      search for GFP variants with novel characteristics, additional autofluorescent
      proteins and alternative techniques of protein labelling. Two recent studies -
      one on tagging with tetracysteine motifs and labelling with biarsenic
      fluorophores of different colours, and the other on GFP tagging and fluorescence
      recovery after photobleaching (FRAP) - show how membrane channels are added and
      removed from gap junctions by using different fluorescent tags to distinguish
      between newly synthesized and older protein populations.

PMID- 12220851
TI  - Human Sir2 and the 'silencing' of p53 activity.
AB  - Members of the evolutionarily conserved silent information regulator 2 (Sir2)
      protein family are nicotinamide adenine dinucleotide (NAD(+))-dependent histone
      deacetylases. In yeast, the founding Sir2 protein is known to function in
      transcriptional silencing processes through the deacetylation of histones H3 and
      H4, thus setting up a repressive chromatin structure. Yeast and Caenorhabditis
      elegans Sir2 are also involved in regulating the life span of these organisms.
      Until recently, the function of mammalian Sir2 family members was completely
      unknown. However, several recent studies have now determined a remarkable
      function for the human SIRT1 protein, which is the closest human homolog of yeast
      Sir2. SIRT1 specifically associates with the p53 tumor suppressor protein and
      deacetylates it, resulting in negative regulation of p53-mediated transcriptional
      activation. Importantly, p53 deacetylation by SIRT1 also prevents cellular
      senescence and apoptosis induced by DNA damage and stress.

PMID- 12220852
TI  - Location, location, location: translational control in development and
      neurobiology.
AB  - Control of gene expression by regulating mRNA translation is essential for proper
      growth and development in species ranging from yeast to mammals. Recently,
      translational regulation has also been implicated in neuronal function, where
      long-lasting changes in synaptic strength and the formation of memory require new
      protein synthesis. Crucial to both developmental and neurobiological function,
      translational control allows for the asymmetric distribution of gene products and
      a rapid and local response to stimulation--as discussed at a recent Serono
      Foundation EMBO Workshop held in Mallorca, Spain.

PMID- 12220861
TI  - Size control in dynamic organelles.
AB  - The mechanisms that control organelle size are unknown. Flagellar length
      regulation is the most accessible of all organelle-size-control problems, and
      experiments on flagellar assembly have provided important clues to how flagellar
      length is controlled, as a balance of assembly and disassembly. I propose that
      the inherent length dependence of intraflagellar transport might be what allows
      the flagellum to reach a defined length. This model of the flagellum might
      represent a general scheme for organelle size control that could apply to any
      organelle whose maintenance involves continuous assembly balanced by disassembly.

PMID- 12220862
TI  - Centromeres become unstuck without heterochromatin.
AB  - In most if not all eukaryotes, sister-chromatid cohesion, which is mediated by
      the chromosomal complex Cohesin, is destroyed by proteolysis at the transition
      from metaphase to anaphase. In metazoans, Cohesin is removed from chromosomes in
      two steps, and the centromere and its associated pericentric heterochromatin
      constitute the last point of linkage between sister chromatids at metaphase.
      Mechanistic insight is now emerging on the way in which cells distinguish
      cohesion at the centromere from cohesion along chromosome arms. We discuss recent
      advances in our understanding of the role of centromeric heterochromatin in
      sister-chromatid cohesion and propose a causal relationship between this
      specialized type of chromatin and the removal by proteolysis of Cohesins that are
      associated with it.

PMID- 12220863
TI  - Chromosome positioning in the interphase nucleus.
AB  - Chromosomes occupy distinct territories in the interphase cell nucleus. These
      chromosome territories are non-randomly arranged within the nuclear space. We are
      only just uncovering how chromosome territories are organized, what determines
      their position and how their spatial organization affects the expression of genes
      and genomes. Here, we discuss emerging models of non-random nuclear chromosome
      organization and consider the functional implications of chromosome positioning
      for gene expression and genome stability.

PMID- 12220864
TI  - Signalling, cell cycle and pluripotency in embryonic stem cells.
AB  - Pluripotent mouse embryonic stem (ES) cells can be expanded in large numbers in
      vitro owing to a process of symmetrical self-renewal. Self-renewal entails
      proliferation with a concomitant suppression of differentiation. Here we describe
      how the cytokine leukaemia inhibitory factor (LIF) sustains self-renewal through
      activation of the transcription factor STAT3, and how two other signals -
      extracellular-signal-related kinase (ERK) and phosphatidylinositol-3-OH kinase
      (PI3K) - can influence differentiation and propagation, respectively. We relate
      these observations to the unusual cell-cycle properties of ES cells and speculate
      on the role of the cell cycle in maintaining pluripotency.

PMID- 12220865
TI  - Vascular cell biology in vivo: a new piscine paradigm?
AB  - Understanding how blood vessels form has become increasingly important in recent
      years yet remains difficult to study. The architecture and context of blood
      vessels are difficult to reproduce in vitro, and most developing blood vessels in
      vivo are relatively inaccessible to observation and experimental manipulation.
      Zebrafish, however, provide several advantages. They have small, accessible,
      transparent embryos and larvae, facilitating high-resolution imaging in vivo. In
      addition, genetic and experimental tools and methods are available for functional
      manipulation of the entire organism, vascular tissues or even single vascular- or
      non-vascular cells. Together, these features make the fish amenable to 'in vivo
      vascular cell biology'.

PMID- 12220866
TI  - The beauty of death.

PMID- 12220868
TI  - Real time odor representations.
AB  - The relative importance of spatial and temporal patterning of odor-evoked
      activity in the olfactory bulb is controversial. Recently, voltage-sensitive dye
      imaging has been used to demonstrate that odor-evoked glomerular patterns evolve
      over time in an odor-specific manner. The results suggest that odor information
      is contained in a combination of spatial and temporal response components.

PMID- 12220869
TI  - Sense and sensibility in the regulation of voltage-gated Ca(2+) channels.
AB  - Voltage-gated Ca(2+) channels are crucial for neurotransmitter release and other
      neuronal functions, and their activity-dependent regulation could underlie
      various aspects of synaptic plasticity. Recent studies have identified Ca(2+)
      sensing proteins involved in Ca(2+)-channel modulation. These have complex
      effects on channel gating, and data suggest that the actions of multiple Ca(2+)
      sensors are important for the fine-tuning of Ca(2+) channel activity.

PMID- 12220870
TI  - Perisynaptic asymmetry of glia: new insights into glutamate signalling.
AB  - Synaptically released glutamate activates extrasynaptic receptors; such actions
      are controlled by glutamate uptake. Recent experimental findings show that there
      are many more glutamate transporters on the postsynaptic than presynaptic side of
      the vicinity of central synapses. This asymmetry favours activation of axonal, as
      opposed to dendritic, extrasynaptic glutamate receptors, thus imposing rule on
      information processing in the brain.

PMID- 12220871
TI  - Teaching old drugs new tricks. Meeting of the Neurodegeneration Drug Screening
      Consortium, 7-8 April 2002, Washington, DC, USA.
AB  - Meeting of the Neurodegeneration Drug Screening Consortium, held on 7-8 April
      2002, Washington, DC, USA.

PMID- 12220872
TI  - Exploring brain connectivity: a new frontier in systems neuroscience. Functional
      Brain Connectivity, 4-6 April 2002, Dusseldorf, Germany.
AB  - Functional Brain Connectivity, held on 4-6 April 2002, Dusseldorf, Germany.

PMID- 12220877
TI  - An emerging molecular and cellular framework for memory processing by the
      hippocampus.
AB  - The hippocampus plays a central role in memory consolidation, a process for
      converting short-term memory into cortically stored, long-lasting memory in the
      mammalian brain. Here, we review recent data and discuss the 'synaptic re-entry
      reinforcement' (SRR) hypothesis, which can account for the role of the
      hippocampus in memory consolidation at both the molecular and systems levels. The
      central idea of the SRR hypothesis is that reactivation of neural ensembles in
      the hippocampus during the consolidation period results in multiple rounds of
      NMDA-receptor-dependent synaptic reinforcement of the hippocampal memory traces
      created during initial learning. In addition, such reactivation and reinforcement
      processes permit the hippocampus to act as a 'coincidence regenerator', providing
      coordinated input that drives the coherent reactivation of cortical neurons,
      resulting in the progressive strengthening of cortical memory traces through
      reactivation of cortical NMDA receptors.

PMID- 12220878
TI  - Phenomics: fiction or the future?
AB  - The ease with which genetic mutations can be induced in or introduced into
      mammalian organisms, such as the mouse, has created a significant need for
      phenotypic analysis. Developments in computer technology, instrumentation and
      bioinformatics, as well as in numerous neuroscience disciplines, will help to
      meet the demands set by the molecular revolution. As a result, the field of
      'phenomics' is being born. This will integrate multidisciplinary research, with
      the goal of understanding the complex phenotypic consequences of genetic
      mutations at the level of the organism. This paper focuses on one of the
      disciplines that show promising developments, behavioral science.

PMID- 12220879
TI  - cGMP and S-nitrosylation: two routes for modulation of neuronal excitability by
      NO.
AB  - The nitric oxide (NO)-cGMP signaling cascade has been implicated in synaptic
      plasticity and, more broadly, in the control of many forms of electrical
      activity. This raises the issue of how these second messengers regulate ion
      channels. The field of ion-channel modulation is dominated by G proteins; NO and
      cGMP are often treated as poor cousins. However, recent advances surveyed here
      could change this perception. A surprising new dimension to NO signaling is the
      direct cGMP-independent action of NO on channel proteins through S-nitrosylation.
      The existence of two effector pathways has important functional implications,
      expanding and enriching the possibilities for modulating neuronal excitability.

PMID- 12220881
TI  - Move to the rhythm: oscillations in the subthalamic nucleus-external globus
      pallidus network.
AB  - Recent anatomical, physiological and computer modeling studies have revealed that
      oscillatory processes at the levels of single neurons and neuronal networks in
      the subthalamic nucleus (STN) and external globus pallidus (GPe) are associated
      with the operation of the basal ganglia in health and in Parkinson's disease
      (PD). Autonomous oscillation of STN and GPe neurons underlies tonic activity and
      is important for synaptic integration, whereas abnormal low-frequency rhythmic
      bursting in the STN and GPe is characteristic of PD. These recent findings
      provide further support for the view that the basal ganglia use both the pattern
      and the rate of neuronal activity to encode information.

PMID- 12220880
TI  - Stressed-out, or in (utero)?
AB  - The molecular and cellular mechanisms by which plasticity is induced in the
      mature CNS (and, specifically, in the hippocampus) by environmental input are
      progressively being elucidated. However, the mechanisms - and even the existence 
      of functional and structural effects of environmental input (and, particularly,
      stress) early in life are incompletely understood. Here, we discuss recent
      evidence that stressful stimuli have a significant impact on neonatal (rat) and
      prenatal (human) hippocampal function and integrity. Stressful signals provoke
      expression and release of neuromodulators, including the peptide corticotropin
      releasing hormone (CRH), leading to activation of CRH receptors on principal
      hippocampal neurons. Although physiological activation of these receptors
      promotes synaptic efficacy, pathological levels of CRH at hippocampal synapses
      contribute to neuronal death. Thus, early-life stress could constitute a 'double
      edged sword': mild stress might promote hippocampal-dependent cognitive function,
      whereas severe stress might impair neuronal function and survival, both
      immediately and in the long-term. Importantly, these CRH-mediated processes could
      be targets of preventive and interventional strategies.

PMID- 12220882
TI  - Axon pathology in neurological disease: a neglected therapeutic target.
AB  - In the C57BL/Wld(S) mouse, a dominant mutation dramatically delays Wallerian
      degeneration in injury and disease, possibly by influencing multi-ubiquitination.
      Studies on this mouse show that axons and synapses degenerate by active and
      regulated mechanisms that are akin to apoptosis. Axon loss contributes to
      neurological symptoms in disorders as diverse as multiple sclerosis, stroke,
      traumatic brain and spinal cord injury, peripheral neuropathies and chronic
      neurodegenerative diseases, but it has been largely neglected in neuroprotective
      strategies. Defects in axonal transport, myelination or oxygenation could trigger
      such mechanisms of active axon degeneration. Understanding how these diverse
      insults might initiate an axon-degeneration process could lead to new therapeutic
      interventions.

PMID- 12220885
TI  - Regulating the isotypic and idiotypic profile of an anti-PC antibody response:
      lessons from peptide mimics.
AB  - Protection against microbial invasion depends not only on the host's ability to
      mount an immune response, but on its ability to mount the correct immune
      response. Whether an antibody response is protective or not depends on both the
      fine antigenic specificity, that may be associated with particular idiotypes and
      epitope binding characteristics, and the isotype, determining antibody effector
      function. Thus, both the variable and the constant region of the antibodies
      induced by a peptide mimotope must be considered when assessing the success of
      any immunization. Phosphorylcholine (PC), an epitope present on the cell-wall C
      polysaccharide of all pneumococcal serotypes, is capable of eliciting a
      protective antibody response to pneumococcal infection in mice and provides an
      attractive model system for understanding the immune response generated by
      peptide mimics. In this system, both the idiotype and isotype of protective
      antibodies have been determined and the characteristics of the in vivo response
      are well described and highly reproducible. We describe here the immune response
      generated by two peptide mimics of PC. Mice immunized with the peptides developed
      antibodies binding PC and C-polysaccharide. The idiotypic profile of the response
      differed depending on the peptide, but never included canonical T15(+)
      antibodies. The isotype of the response to peptide mimics differed depending on a
      combination of peptide and adjuvant, and included both IgG2a and IgG2b antibodies
      which are not typically seen in the response to PC. Thus, peptide mimotopes may
      elicit anti-polysaccharide responses, but fail to elicit the idiotypes and
      isotypes observed in the protective response to the microbial antigen.

PMID- 12220886
TI  - Idiotypic mimicry of a catalytic antibody active site.
AB  - We have previously described three catalytic antibodies (Ab1s) raised against
      human erythrocyte acetylcholinesterase (AChE). These antibodies both recognise
      and resemble AChE in their reaction with substrates and appear with a relatively
      high frequency. We do not know, however, why catalytic activity should have
      developed in response to a ground state antigen. This question has implication
      for autoimmune disorders, which are frequently characterised by the presence of
      catalytic antibodies, many of which have cytotoxic effects. In this study, we
      raised anti-idiotypic (Ab2) and anti-anti-idiotypic (Ab3) antibodies to a
      catalytic Ab1 and examined their properties. None of the Ab2s showed catalytic
      activity, whereas four of the Ab3s did, an incidence of 1.26%. No contamination
      of antibody preparations with either AChE or butyrylcholinesterase (BChE) was
      found. Immunisation of mice with AChE, as well as AChE complexed with various
      inhibitors, resulted in a significant increase in catalytic immunoglobulins in
      the serum, compared with non-immunised mice and mice immunised with the Ab1.
      There appears to be considerable resemblance between Ab1s and Ab3s, but there are
      also significant differences between the two groups. All the antibodies were
      inhibited by phenylmethylsulphonyl fluoride (PMSF), indicating the presence of a
      serine residue in their active sites and were inhibited by the cholinesterase
      active site inhibitors tetraisopropyl pyrophosphoramide (iso-OMPA) and
      pyridostigmine. The Ab3s resembled the Ab1s in their ability to hydrolyse both
      acetylthiocholine (ATCh) and butyrylthiocholine (BTCh). However, the Ab3s appear
      to be better catalysts, having significantly reduced K(M) values (for ATCh but
      not BTCh) and increased turnover numbers (K(cat)), rate enhancements
      (K(cat)/K(uncat)) and K(cat)/K(M) ratios. The Ab3s also had reduced affinities
      for cholinesterase anionic site inhibitors (edrophonium, tetramethylammonium and
      BW284c51) and no affinity at all for the AChE peripheral anionic site (PAS)
      inhibitor fasciculin. All the antibodies recognise, to some degree, the PAS of
      AChE, shown by their ability to inhibit AChE, to compete with peripheral site
      inhibitors and to block AChE-mediated cell adhesion, a property of the site.
      These results indicate idiotypic mimicry of the catalytic antibody's active site,
      suggesting that the catalytic activity is due to affinity maturation of
      immunoglobulin genes in response to a specific antigen, namely, the PAS of AChE.
      Further studies are required to determine the structural features of this ground
      state antigen responsible for the development of catalytic activity.

PMID- 12220887
TI  - Overexpression of TIAP/m-survivin in thymocytes enhances cell proliferation.
AB  - TIAP/m-survivin, a member of the inhibitor of apoptosis (IAP) protein family, is
      expressed in a cell cycle dependent manner. It is strongly expressed in various
      subsets of thymocytes. To investigate a role of TIAP/m-survivin in thymocytes,
      mice carrying the lck-TIAP transgene were established. Two out of six transgenic
      mice expressed large amounts of TIAP mRNA and protein in thymocytes. Although T
      cell development and apoptosis of thymocytes were largely unaffected in lck-TIAP
      mice, transgenic thymocytes displayed hyperproliferation in response to PMA and
      ionomycin but not to anti-CD3 antibody. Thus, overexpression of TIAP/m-survivin
      augments cell proliferation of thymocytes to a certain stimulation.

PMID- 12220888
TI  - Molecular and genetic characterizations of five pathogenic and two non-pathogenic
      monoclonal antiphospholipid antibodies.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disease that is characterized by
      thrombosis, recurrent fetal loss and thrombocytopenia. Antiphospholipid
      antibodies, detected by enzyme-linked immunoabsorbent assays (aCL) and/or in
      vitro blood clotting assays (LAC) are strongly associated with APS. Both the
      molecular structures used by pathogenic antiphospholipid antibodies and the
      genetic mechanisms leading to their production are unknown. We describe here the
      variable region genes of seven IgG antiphospholipid antibodies derived from two
      APS patients. Of these, five are pathogenic as defined in a mouse model of
      thrombosis and two are not. Analyses of the expressed variable region genes show
      no preferential V gene usage. However, similar to anti-DNA antibodies, pathogenic
      antiphospholipid antibodies contain an increased number of arginine residues in
      the third complimentarity-determining region (CDR3) of their H chains. The
      increased accumulation of arginine residues in the V(H) CDR3 may act to enhance
      antigen binding, promote disease and point to the importance of the H chain in
      the pathogenic potential of certain antiphospholipid antibodies.

PMID- 12220889
TI  - Analysis of two IgM isotypes in Atlantic salmon and brown trout.
AB  - Atlantic salmon (Salmo salar) possesses two distinct subpopulations of polymeric
      IgM which are separable by anion exchange chromatography. Consistent with this
      finding there are two isotypic IgM heavy chain genes, CmuA and CmuB, in the
      genome of this species, presumably as a result of ancestral tetraploidy. In the
      present study it was shown that IgM of brown trout (Salmo trutta) is also
      separated into two subpopulations by anion exchange chromatography, while IgM of
      rainbow trout (Oncorhynchus mykiss) and Arctic char (Salvelinus alpinus) are
      eluted in one peak. Molecular cloning of IgM heavy chain cDNAs from brown trout
      revealed messages of two distinct constant region genes, named CmuA and CmuB. As
      deduced from the translated cDNA sequences (and in agreement with isoelectric
      focusing of the corresponding proteins) the mean pI values of the heavy chains in
      brown trout differ with only 0.14 units, in comparison to a 0.67 unit difference
      in salmon. Based on the present sequence analysis we suggest that an additional
      cysteine near the C-terminus of CmuB is critical in relation to the fractionation
      of IgM by anion exchange chromatography, for example by altering the overall
      structure of the IgM polymer and the exposure of charged residues. Most likely,
      the Cmu subvariant with the characteristic extra cysteine residue arose in the
      ancestor of Atlantic salmon and brown trout, i.e. after the three genera Salmo,
      Oncorhynchus and Salvelinus radiated.

PMID- 12220890
TI  - A retro-inverso peptide analogue of influenza virus hemagglutinin B-cell epitope
      91-108 induces a strong mucosal and systemic immune response and confers
      protection in mice after intranasal immunization.
AB  - In this study, a novel approach for the development of a peptide-based vaccine
      has been tested. We investigated the possibility of replacing an all-L amino acid
      peptide sequence corresponding to the protective B-cell epitope hemagglutinin
      (HA) 91-108 from influenza HA with a retro-inverso analogue encompassing this
      sequence. Retro-inverso peptides are composed of D-amino acids assembled in a
      reverse order from that of the parent L-sequence, thus maintaining the overall
      topology of the native sequence. This explains the observed antigenic cross
      reactivity with anti-influenza virus antibodies. Mice immunized intranasally with
      the ovalbumin-conjugated retro-inverso analogue and cholera toxin as an adjuvant,
      produced strong systemic (serum IgG) and mucosal (lung IgA) antibody responses,
      and were protected against intranasal challenge with a lethal dose of influenza
      virus. The weight loss pattern in the protected group indicated that the
      vaccinated animals developed a disease of low severity resulting in a quick
      recovery. Furthermore, splenocytes of the immunized mice cultured in the presence
      of inactivated influenza virus, secreted high levels of IFN-gamma. The half-life
      of the retro-inverso analogue in the presence of lung homogenate proteases was at
      least 700 times greater than that of the parent L-peptide. These results
      demonstrate that peptidomimetic analogues with high resistance to proteolytic
      degradation are very effective immunogens when administered via the intranasal
      route, inducing protective immunity against a viral infection. This approach
      might be advantageous for vaccine development.

PMID- 12220891
TI  - Molecular signatures of antinuclear antibodies-contributions of heavy chain CDR
      residues.
AB  - A database of the Ig heavy chains of 143 anti-ssDNA, 103 anti-dsDNA and 23 anti
      nucleosome antinuclear antibodies (ANAs) was constructed, with no clonal overlap,
      gleaning from published literature. In comparison to the Kabat database of
      antibodies (N>3600), ANAs (total=269) demonstrated several significant changes,
      particularly in the incidence of charged or polar residues, in their CDR regions.
      In particular, anti-dsDNA ANAs differed significantly from anti-ssDNA ANAs in
      having (a) more 'D' residues at H31 and more 'Y' residues at H33, in CDR1, (b)
      significantly different distributions of charged or polar residues at H53, H55
      and H56 of CDR2, and (c) more 'R' residues at H95-H100 of CDR3. Whereas, the
      differences in CDR1 and CDR3 are likely to characterize anti-dsDNA ANAs encoded
      by all VH families, the sequence differences in CDR2 are likely to be VH family
      specific. Finally, among anti-dsDNA ANAs, there was an enrichment of VH1/J558
      germline genes (notably, VH 45.21.1), which bear germline-encoded amino acid
      residues in their CDR regions that may potentially facilitate nuclear antigen
      binding. This ANA heavy chain database thus constitutes a useful resource for
      analyzing the molecular requirements for nuclear antigen reactivity.

PMID- 12220892
TI  - In vitro molecular evolution of antibody genes mimicking receptor revision.
AB  - Antibody evolution in vivo proceeds mainly by stepwise improvements, accomplished
      by single base pair substitutions. Lately, receptor revision, i.e. exchange of
      large parts of the V gene for another sequence, has been suggested to provide a
      complementary route for affinity maturation. By employing a receptor revision
      like evolution process in vitro using combinatorial libraries and phage display
      selection, we demonstrate here that maturation of a clone may preferentially
      proceed through exchange of a large gene segment rather than via minor sequence
      changes. These modifications of a CD40-specific human antibody fragment outline
      how receptor revision like events may provide an advantage to a particular
      clonotype put under selective pressure.

PMID- 12220893
TI  - Generation and characterization of transgenic mice expressing cobra venom factor.
AB  - Cobra venom factor (CVF), the anticomplementary protein in cobra venom, activates
      the alternative complement pathway, eventually leading to complement consumption.
      Here, we describe the development of a transgenic mouse model for CVF. We
      generated a DNA construct containing the full-length cDNA for single-chain pre
      pro-CVF. Expression of CVF was controlled by the alpha(1)-antitrypsin promoter to
      achieve liver-specific expression. Linearized DNA was microinjected into murine
      ovary cells (strain CD(2)F(1) (BALB/cxDBA/2J)) and the newborn mice were analyzed
      for stable integration of CVF DNA. After establishing the transgene, mice were
      propagated in a BALB/c background. The CVF mRNA was detected in the liver and, in
      some animals, in the kidney. CVF protein was detected in small amounts in the
      serum. Serum complement hemolytic activity in CVF-transgenic mice was virtually
      absent. The concentration of plasma C3 was significantly reduced. The CVF
      transgenic animals show no unusual phenotype. They provide an animal model to
      study the effect of long-term complement depletion by continued activation, as
      well as the role of complement in host immune response and pathogenesis of
      disease.

PMID- 12220894
TI  - Variable binding affinities for allergen suggest a 'selective competition' among
      immunoglobulins in atopic and non-atopic humans.
AB  - Atopy is a persistent, aberrant humoral response to certain classes of proteins
      (allergens) characterized by the presence of allergen-specific IgE. Yet, in both
      atopic and non-atopic individuals, allergen-specific responses involving the IgA
      and IgG subclasses have been observed, which evidence does not support models
      suggesting inherited differences in sensitivity to certain protein classes. Using
      the major ragweed component Amb a 1 as a model allergen, we assessed the humoral
      responses in three groups of unrelated donors: (A) atopic, ragweed sensitive; (B)
      atopic, but not ragweed sensitive; (C) non-atopic. As expected, Amb a 1-specific
      IgE was present in group A only. However, there were essentially no differences
      in the relative proportions of Amb a 1-specific IgA(1,2) and IgG(1-4) among the
      groups. We also determined the Amb a 1 binding affinities for IgG(1) and IgG(4)
      in the three groups, and compared these to Amb a 1-specific IgE binding
      affinities in group A. Group A donors' Amb a 1-IgE had extremely high affinities
      (10(8) to 10(11)M(-1)), but their Amb a 1-IgG(1) and Amb a 1-IgG(4) affinities
      were significantly lower (10(7) to 10(10)M(-1)). The average IgG(4) binding
      affinities in groups B and C were slightly higher than that of IgG(4) in group A,
      although not statistically significant. However, the IgG(1) affinity for Amb a 1
      among group C, non-atopic donors was significantly elevated and comparable to the
      IgE affinity observed in group A, ragweed atopics. Inhibition studies with
      allergen-specific IgE-free serum showed that all isotypes recognized the major
      epitopes seen by IgE. These results suggest that there may be a "selective
      competition" among isotypes for allergens that is driven by the ability to
      produce high affinity, allergen-specific immunoglobulins.

PMID- 12220896
TI  - Conservation of gene co-regulation in prokaryotes and eukaryotes.
AB  - Genes that are part of the same operon in prokaryotes, or have the same
      expression pattern in eukaryotes, are transcriptionally co-regulated. If genes
      are consistently co-regulated across distantly related organisms, the genes have
      closely associated functions. It has been shown previously that such genes have a
      strong tendency to belong to the same protein complex in prokaryotes, and we show
      by an analysis of the sequences and their expression in the yeast Saccharomyces
      cerevisiae and the worm Caenorhabditis elegans that this is also true for
      eukaryotes. Our analysis reveals that the number of conserved co-regulated genes
      is small in eukaryotes, as has been shown previously in prokaryotes, indicating
      that there are extensive variations in the gene regulatory network across
      organisms.

PMID- 12220898
TI  - Making 'random amplification' predictable in whole genome analysis.
AB  - One of the remaining obstacles to large-scale genetic mapping is the lack of an
      efficient way to genotype hundreds of thousands of genetic markers. Recently
      Jordan et al. reported that the 'random' sequences amplified by degenerate
      oligonucleotide primer (DOP)-PCR can be precisely mapped onto the human genome
      sequence and that it is possible to predict which DNA sequences will be amplified
      by a particular degenerate primer.

PMID- 12220899
TI  - Gene watching: how to get a closer look.

PMID- 12220903
TI  - GP130 stimulation and the maintenance of stem cells.
AB  - Recent advantages with the cultivation of adult and embryonic stem cells have
      raised hopes for therapeutic applications of such cells in the treatment of
      neurodegenerative diseases and cancer. Cultivation of stem cells on feeder cells
      or treatment of the cells with cytokines is necessary to maintain stem cells in
      an undifferentiated state and to keep their pluripotency. In particular, the
      cytokine leukemia inhibitory factor (LIF) has been used to cultivate murine
      embryonic stem (ES) cells in the absence of feeder cells. For unknown reasons,
      LIF does not evoke the same effect on rat or human stem cells. This article
      summarizes what is known about, and the problems associated with, the cultivation
      of stem cells and suggests experimental strategies that might help to overcome
      these difficulties.

PMID- 12220904
TI  - Trehalose production: exploiting novel approaches.
AB  - Trehalose (alpha-D-glucopyranosyl alpha-D-glucopyranoside) is a unique sugar
      capable of protecting biomolecules against environmental stress. It is a stable,
      colorless, odor-free and non-reducing disaccharide, and is widespread in nature.
      Trehalose has a key role in the survival of some plants and insects, termed
      anhydrobionts, in harsh environments, even when most of their water body is
      removed. The properties of these types of organisms drove attention towards the
      study of trehalose. Since then, it proved to be an active stabilizer of enzymes,
      proteins, biomasses, pharmaceutical preparations and even organs for
      transplantation. Recently, trehalose has been accepted as a safe food ingredient
      by the European regulation system following approval by the US Food and Drug
      Administration. The wide range of applications of this sugar has increased the
      interest of many research groups into the development of novel and economically
      feasible production systems. This article provides a comprehensive review of the
      current achievements in the biotechnological production of trehalose.

PMID- 12220905
TI  - Meeting the consumer challenge through genetically customized wine-yeast strains.
AB  - Wine producers are facing intensifying competition brought about by a widening
      gap between wine production and wine consumption, a shift of consumer preferences
      away from basic commodity wine to top quality wine, and economic globalization.
      Consequently, they are calling for a total revolution in the 'magical' world of
      wine. The process of transforming the wine industry from a production- to a
      market-orientated industry results in an increasing dependence on, amongst
      others, biotechnological innovation. Market-orientated wine-yeast strains are
      currently being developed for the cost-competitive production of wine with
      minimized resource inputs, improved quality and low environmental impact. The
      emphasis is on the development of Saccharomyces cerevisiae strains with improved
      fermentation, processing and biopreservation abilities, and capacities for an
      increase in the wholesomeness and sensory quality of wine.

PMID- 12220906
TI  - Optimizing lipases and related enzymes for efficient application.
AB  - Although numerous reactions have been performed using lipases and related enzymes
      (e.g. esterases and phospholipases), it is still a challenge to identify the most
      suitable biocatalyst and best reaction conditions for an efficient application.
      Frequently used methods such as immobilization and optimization of the reaction
      medium cannot be transferred from one reaction system or substrate to another.
      However, in the past few years, rational protein design and directed evolution
      have emerged as efficient alternative methods to optimize biocatalytic reactions.

PMID- 12220907
TI  - Preparative protein refolding.
AB  - The rapid provision of purified native protein underpins both structural biology
      and the development of new biopharmaceuticals. The dominance of Escherichia coli
      as a cellular biofactory depends on technology for solubilizing and refolding
      proteins that are expressed as insoluble inclusion bodies. Such technology must
      be scale invariant, easily automated, generic for a broad range of similar
      proteins and economical. Refolding methods relying on denaturant dilution and
      column-based approaches meet these criteria. Recent developments, particularly in
      column-based methods, promise to extend the range of proteins that can be
      refolded successfully. Developments in preparing denatured purified protein and
      in the analysis of protein refolding products promise to remove bottlenecks in
      the overall process. Combined, these developments promise to facilitate the rapid
      and automated determination of appropriate refolding conditions and to simplify
      scale-up.

PMID- 12220909
TI  - The relationship between skeletal muscle proteolysis and ubiquitin-proteasome
      proteolytic pathway in burned rats.
AB  - Negative nitrogen balance and accelerated muscle protein breakdown are
      characteristics of burn injury. The mechanism by which muscle proteolysis occurs
      may be activation of the ubiquitin-proteasome pathway, but needs to be further
      elucidated. The aim of this study was to gain more insight into the role of
      ubiquitin-proteasome pathway in muscle proteolysis, after burn injury in a rat
      burn injury model. The proteolytic rates and mRNA expression of ubiquitin, E2
      14K, and subunit RC2 in extensor digital longus (EDL) and soleus (SOL) muscle
      were determined by amino acid analyzer and Northern blot, respectively. The
      results were as follows: the total and myofibrillar proteolytic rate of EDL
      muscle increased markedly, especially at 12 and 24h post-burn. The levels of
      2.4kb mRNA for ubiquitin, 1.2kb mRNA for E2-14K (a rate-limiting and regulated
      enzyme for conjugation of ubiquitin with protein substrate) and mRNA for subunit
      RC2 (the largest subunit of 20S proteasome) predominantly increased in EDL muscle
      after the stimulation of burn injury. No significant changes in proteolytic rate
      and transcription of ubiquitin, E2-14K, and subunit RC2 in SOL muscle were
      observed. There was a significantly positive correlation between the proteolytic
      rate and the levels of 2.4kb mRNA for ubiquitin, 1.2kb mRNA for E2-14K, or mRNA
      for subunit RC2. The results indicated that muscle wasting after burn injury was
      mainly due to the accelerated breakdown of myofibrils, and EDL muscle was more
      sensitive to burn injury than SOL muscle. The activation of ubiquitin-proteasome
      pathway was one reason for the enhanced protein catabolism in skeletal muscle.
      This is the first demonstration of upregulated expression of E2-14K and subunit
      RC2 in muscle, in response to burn injury, and it provides a clue to reduce
      muscle wasting by specifically inhibiting the specific enzymes or subunits
      involved in the enhancement of the activity of ubiquitin-proteasome pathway after
      burn injury.

PMID- 12220910
TI  - Alterations of acute phase reaction and cytokine production in patients following
      severe burn injury.
AB  - To determine the acute immunologic reaction, mediated by cytokines, interleukines
      (ILs) and growth factors and the susceptibility to infections and sepsis after
      severe burn injury a prospective, single unit, longitudinal study of acute phase
      reactants and mediators who performed. After approval by the ethics committee of
      our hospital, we investigated the plasma concentrations of IL-2, -6, -8, -10, and
      -13, the soluble IL-2 receptor (sIL-2R), and the acute phase proteins
      procalcitonin (PCT) and C-reactive protein (CRP) at admission and every 3 days in
      24 patients over a time course of 28 days after thermal injury and categorized by
      percent burn: < or =30% (group 1; n=12) and >30% (group 2; n=12). Shortly after
      burn injury we found higher concentrations of IL-2, -6, -10 and PCT in those
      patients >30% TBSA. During the study period, we found significant higher levels
      of acute phase proteins, IL-6 and -8 in patients >30% TBSA. The incidence of SIRS
      and MODS was three times increased in patients >30% TBSA. Our results show
      different patterns of cytokines and acute phase proteins in patients with
      different burned surface areas over a long time and continuous monitoring of a
      more distinct inflammatory response in these patients.

PMID- 12220911
TI  - Only some septicaemic patients develop hypernatremia in the burn intensive care
      unit: why?
AB  - From April 1993 to January 2000, 105 patients in the burn intensive care unit
      (BICU) that developed septicaemia in the course of their treatment were studied
      retrospectively to investigate as to why only 36 septicaemic patients (34%)
      developed hypernatremia (serum sodium >150mmol/l). Septicaemic burn patients who
      developed hypernatremia were found to have a higher incidence of inhalation
      injury and a larger burn area (TBSA) signifying greater free water losses in the
      face of increasing fluid requirements. Patients who developed hypernatremia
      showed a characteristic pattern of septicaemia: early onset, multiple episodes,
      polymicrobial, need for multiple antibiotics, longer duration and a higher
      mortality, indicating a more severe degree of sepsis. The level of incapacitation
      either from the burn itself, mechanical ventilation or from impaired mental
      status leading to an inadequate free water intake was more in septicaemic
      patients who developed hypernatremia. Increased urinary free water losses and
      solute diuresis from hyperglycemia were significant factors in the development of
      hypernatremia. Patients who were treated with early wound excisions were less
      prone to develop hypernatremia when compared to those who did not undergo early
      wound excision. The close association between the onset of hypernatremia and the
      onset of septicaemia noted in this study suggests the use of hypernatremia as a
      marker for septicaemia in burn patients. Hypernatremia in a septicaemic burn
      patient is multi-factorial and a thorough understanding of the underlying factors
      will help prevent the onset and progress of hypernatremia.

PMID- 12220912
TI  - Exploration of coping patterns in burned adults: cluster analysis of the coping
      with burns questionnaire (CBQ).
AB  - The aim of this study was to investigate coping patterns, health status and
      personality traits in burned adults. Subjects were 161 burn patients treated at
      the Uppsala University Hospital between 1980 and 1995. Measures were the coping
      with burns questionnaire (CBQ), the burn specific health scale-brief (BSHS-B) and
      the Swedish universities scales of personality (SSP). The CBQ was subjected to a
      K-means cluster analysis and three clusters were derived: extensive, adaptive,
      and avoidant copers. Extensive copers used the most coping and took an
      intermediate role regarding health status and the personality trait of
      neuroticism. Adaptive copers preferred the strategies emotional support and
      optimism/problem solving, and had the highest health status ratings. Avoidant
      copers preferred the strategy avoidance and reported the lowest use of emotional
      support and optimism/problem solving. They had the lowest health status ratings
      and the highest ratings on neuroticism and aggressiveness. The clusters did not
      differ in severity of injury or time since injury. In conclusion, coping patterns
      can be discerned among burn patients, and those individuals preferring avoidance
      and lacking other coping options displayed more maladaptive traits and poorer
      health status years after the burn.

PMID- 12220913
TI  - An analysis of 11,196 burn admissions and evaluation of conservative management
      techniques.
AB  - We present an 8-year analysis (1993-2000) of 11,196 burn admissions with an
      average of 116.6 patients per month. Patients were largely treated by
      conservative techniques. The mean burn percentage was 50.35. Almost 80% of
      admissions were in the 16-55 years age group. Paediatric and geriatric burns were
      17.1 and 3.1%, respectively. Flame burns accounted for 82.15% of admissions and
      of these 77.5% were sustained in the kitchen. A total of 35.32% of flame
      accidents were due to malfunctioning kerosene pressure stove. The overall
      mortality was 51.80%. These figures need further qualification because 46.8% of
      patients had more than 50% BSA burns and 50.72% patients reported to the hospital
      more than 6h after sustaining burns. Patients with <60% BSA burns, and who were
      received within 6h of injury had a mortality of 23% only. Significantly,
      1078/1952 deaths (55.23%) of patients <60% BSA burns took place in first 6 days
      of admission when 3639 patients with <60% BSA injury were received more than 6h
      after burn injury. This reflects that even if economic constraints preclude one
      from having the best infrastructure reasonable mortality rates are still
      achievable with conservative line of management, even in face of a heavy work
      load. This also makes one question the cost effectiveness of high cost technology
      in burn management.

PMID- 12220914
TI  - Four years of burn injuries in a Red Cross hospital in Afghanistan.
AB  - This study examines the epidemiology and mortality of patients admitted with
      burns to a Red Cross hospital in Afghanistan between 1996 and 2000. Three hundred
      and eighty-eight cases were reviewed retrospectively (57% male, 43% female) with
      a median age of 8 years. Sixty-three percent were children. Scalds (44%) were the
      commonest injury followed by fire (37%). The median total body surface area
      burned (TBSA) was 15%. Forty-six percent of the patients required surgical
      debridement and 11% underwent delayed skin grafting. Overall, median duration of
      stay was 7 days. The mortality rate was 16% (M:F, 1.1:1) and fire was the
      commonest cause of fatal burns. The median TBSA of fatal burn was 40%. There were
      no survivors with burns greater than 45% TBSA. Multiple organ failure and sepsis
      were the cause for most of the deaths.

PMID- 12220915
TI  - Analysis of 1089 burn patients in province of Kurdistan, Iran.
AB  - Burn injuries still produce a significant morbidity and mortality in Iran. This
      study was carried out to analyze the epidemiology, mortality, and current
      etiological factors of 1089 burn patients in the province of Kurdistan in the
      west of Iran during the 6 years from 21 March 1994 to 20 March 2000. There were
      two burn centers in Kurdistan, serving 1.4 million people in an area of 28,000
      km(2). The incidence rate of burn hospitalization was 13.5 per 100,000 person
      years. The median age was 18 years with 58% of the patients under 20 years. The
      median Body Surface Area (BSA) burned was 40%. Incidence rate of burns for
      females was 18 per 100,000 person-years and 9.1 per 100,000 person-years for
      males (P((2))<0.000001). Also there was a statistically significant association
      between mortality rate and age groups/gender/BBS (P((2))<0.000001). Flame was the
      most common type of burn (694/1089, 63.7%). There was also a significant
      correlation between the age groups and types of burn (P((2))<0.000001). Ninety
      one percent (991/1089) of the burns were unintentional (12.3 per 100,000 person
      years), while suicide attempts by burning for the population aged 13 and older
      accounted for 12.7% (98/771) (2 per 100,000 person-years). The mortality rate was
      4.5 per 100,000 person-years. The study results provide a valuable baseline by
      which to assess future efforts directed toward the prevention of burn injuries in
      Kurdistan.

PMID- 12220916
TI  - MRSA-retrospective analysis of an outbreak in the burn centre Aachen.
AB  - The growing interest in methicillin-resistant Staphylococcus aureus (MRSA) has
      been caused by its increased appearance in hospital and community populations. In
      our burn centre, an outbreak of MRSA was noticed during an 8-month period. We
      were able to isolate MRSA in eight patients. DNA analysis by pulsed-field gel
      electrophoresis (PFGE) demonstrated the development of five different strains
      during this period. Only two patients developed an infection caused by MRSA
      colonisation. The infections were proven by positive blood culture or catheter
      colonisation. One patient developed a clinical vancomycin-resistant sepsis which
      was treated successfully with the additional application of
      Quinupristin/Dalfopristin. THIS ANALYSIS SHOWS THAT: (1) the development of MRSA
      in a burn unit is often created in a single patient by long-term antibiotic
      therapy and not a result of cross-infection, (2) manifest MRSA infection seldom
      occurs even in colonised burn patients, and (3) a clinically vancomycin-resistant
      MRSA infection in burn patients can be treated sufficiently with
      Quinupristin/Dalfopristin.

PMID- 12220917
TI  - Role of artificial neural networks in prediction of survival of burn patients-a
      new approach.
AB  - A burn patient may require the most complicated treatment regimes encountered
      among trauma victims. Predicting the outcome of such treatment depends on several
      factors which have non-linear relationships. Traditional methods in prediction
      are "logistic regression" and "maximum likelihood". In this study, an artificial
      neural network (ANN) is used for computing survival among burn patients admitted
      to the "Motahary Burn Center", during a 1 year period (1996-1997). Fifteen
      different observations, such as total body surface area (TBSA), rescue time,
      admission period, surgery, inhalation injuries, etc. were obtained,
      retrospectively. A normal feed forward ANN was developed by Thinkspro software.
      It has 15 input-units, two hidden layers, and one output-unit. Survival was
      higher in males, those in whom early fluid resuscitation had been initiated and
      in patients in the middle of the age spectrum (P<0.0001). Strong correlations
      with these factors were noted. In the training phase, the ANNs accuracy reached
      90%. In this study, the ANN has been applied for the first time to predict burn
      victim survival. This study can enable a different view point to help burn center
      physicians in the prediction of survival of their patients.

PMID- 12220918
TI  - Hot iron burns in children.
AB  - Burns for contact with irons are an important preventable cause of burns in
      children. The objective of this study, was to document and describe these burns.
      The report describes 50 children with iron burns who were treated at our Burns
      Unit between 1997 and 2001. METHODS: Prospective data collection demographics,
      nature of contact with iron, site, body surface area (BSA), medical and surgical
      interventions and complications and hand preference were examined. RESULTS: The
      median of age patients was 17 months. The majority of burns were caused by
      touching the iron (44%) or by pulling the cord (38%). Most of the children were
      supervised (74%) and the iron was switched off in 34% of the injuries. Seventy
      six percent of children sustained hand burns. Although, burn areas were
      relatively small, 36% required grafting. Residual scarring occurred in 42% and
      contractures in 10%. Surgical release of contractures was required in 4%.
      CONCLUSION: There is clearly a wide scope for prevention of hot iron burns. A
      public education campaign is now planned including: leaflets distributed at the
      point of purchase of the iron, public education via media outlets and lobbying of
      iron manufacturers to improve safety features.

PMID- 12220919
TI  - Nuclear imaging of the brain in electrical burn patients.
AB  - Patients surviving high-voltage electrical injury may have early or delayed
      sequelae. Technetium-99m (Tc-99m) hexamethylpropyleneamine oxime (HMPAO) is a
      lipid soluble brain perfusion agent rapidly retained in the brain tissue in
      proportion to regional cerebral blood flow without any redistribution. The aim of
      this study is to point out the importance of nuclear imaging of the brain and
      estimate the possible sequelae due to high-voltage electric injured patients.
      Brain perfusion analyses may help the early detection of cerebral blood
      disturbances and to inform both patient and surgeons about the possible
      neurological complications in electric burn patients.

PMID- 12220920
TI  - The use of temporary diverting colostomy to manage elderly individuals with
      extensive perineal burns.
AB  - The regimen of burn treatment for five elderly individuals who had sustained
      burns that had involved the perineum included formation of colostomy to divert
      fecal passage. The inclusion of diverting colostomy in this group of patients had
      made the management of burn wound that had included eventual skin grafting
      technically easy. A total of 168 patients were admitted to the Burn Unit at the
      Kagoshima City Hospital between 1997 and 2000. There were 36 patients who had
      perineal involvement. Of these, there were five elderly patients aged 60 years or
      older. There were two men and three women who were between 60 and 81 years of
      age. The mean age was 72 years. The total body surface involvement varied between
      7 and 55% with an average body surface involvement of 30%. The sigmoid colon was
      as the colostomy site. Although, two patients died of injury, the morbidities
      associated with colostomy procedure were nil.

PMID- 12220921
TI  - The burned female breast: a report on four cases.

PMID- 12220922
TI  - Reversible hyperintense T2 MRI lesions of basal ganglia after an electrical
      injury.

PMID- 12220923
TI  - Severe hypokalemia as a cause of acute transient paraplegia following electrical
      shock.
AB  - Transient lower extremity paralysis has been previously reported following high
      voltage electrical injury. The following case report describes an unusual
      presentation of transient acute flaccid lower extremity paralysis following a
      high voltage electrical injury associated with profound hypokalemia and acid/base
      abnormalities similar to the periodic paralysis syndrome. The patient's symptoms
      resolved with correction of severe hypokalemia. Potential mechanisms for a
      metabolic neuromuscular disorder induced by electrical injury are proposed.

PMID- 12220924
TI  - Fluid resuscitation for burns: a double edge weapon.

PMID- 12220925
TI  - Burn victims in the Republic of Yemen.

PMID- 12220926
TI  - Mummy's little helper.

PMID- 12220928
TI  - Clonus is a sign of upper motor neuron lesion, not a different neurological
      complication.

PMID- 12220931
TI  - Access roads for RAG-ged terrains: control of T cell receptor gene rearrangement
      at multiple levels.
AB  - Antigen-specific immune response requires the generation of a diverse antigen
      (Ag)-receptor repertoire. The primary repertoire is generated through somatic
      gene rearrangement and molded by subsequent cellular selection. Constraints
      during gene recombination influence the ultimate shape of the repertoire. One
      major control mechanism of gene rearrangement, investigated for many years, is
      exerted through regulated chromosomal accessibility of the recombinase to the
      antigen receptor loci. More recent studies began to explore the role of
      interactions between the recombinase and its cognate recognition DNA sequences.
      The emerging results suggest that formation of the primary repertoire is
      controlled by two, partially independent factors: chromosomal accessibility and
      direct recombinase-DNA interactions.

PMID- 12220932
TI  - Regulation of thymocyte differentiation: pre-TCR signals and beta-selection.
AB  - The specificity of the adaptive immune response is, in part, dependent on the
      clonal expression of the mature T cell receptor (TCR) on T lymphocytes. One
      mechanism regulating the clonality of the TCR occurs at the level of TCR-beta
      gene rearrangements during lymphocyte development. Expression of a nascent TCR
      beta chain together with pre-Talpha (pTalpha) and CD3 molecules to form the pre
      TCR complex, represents a critical checkpoint in T cell differentiation known as
      beta-selection. Indeed, failure to generate a functionally rearranged TCR-beta
      chain at this stage of development results in apoptosis. Signals derived from the
      pre-TCR complex trigger a maturation program within developing thymocytes that
      includes: rescue from apoptosis; inhibition of further DNA recombination at the
      TCR-beta gene locus (allowing for the clonality of antigen receptor expression;
      allelic exclusion); and induction of proliferation and differentiation. The
      signaling mechanisms that control this developmental program remain largely
      undefined. Here, we discuss recent evidence investigating the molecular
      mechanisms that regulate thymocyte differentiation downstream of pre-TCR
      formation.

PMID- 12220933
TI  - Regulation of surface expression of the human pre-T cell receptor complex.
AB  - Considerable progress has recently been made in defining the role that pre
      antigen receptor complexes, namely the pre-T and pre-B cell receptors, play in
      lymphocyte development. It is now established that these receptors direct, in a
      similar way, the survival, expansion, clonality and further differentiation of
      pre-T and pre-B lymphocytes, respectively. However, less is known about the
      mechanisms which ensure that only minute amounts of pre-TCR and pre-BCR reach the
      plasma membrane of developing lymphocytes. In this review, we discuss the
      implications of recent experimental approaches which address the developmental
      regulation of human pre-TCR expression and the molecular mechanisms that control
      surface pre-TCR expression levels.

PMID- 12220934
TI  - The pre-B cell receptor and its role in proliferation and Ig heavy chain allelic
      exclusion.
AB  - The pre-B cell receptor (pre-BCR) is composed of the immunoglobulin (Ig) heavy
      (microH) chain and the surrogate light chain encoded by VpreB and lambda5. The
      pre-BCR has been implicated in precursor B cell proliferation, differentiation
      and IgH chain allelic exclusion. B cell development in mice lacking the
      transmembrane form of microH chain is blocked at the precursor B cell stage: the
      cells cannot proliferate or differentiate further and the IgH locus is
      allelically included. In mice lacking lambda5, the precursor B cells, although
      unable to proliferate, can nonetheless differentiate, whereas the IgH locus is
      allelically excluded. It was, therefore, postulated that microH chain together
      with VpreB could form a pre-BCR-like receptor that would allow IgH allelic
      exclusion but not proliferation. In mice lacking both VpreB genes, precursor B
      cells do not proliferate but are able to differentiate. Surprisingly, the IgH
      locus is allelically excluded. This suggests that microH chains find other
      partner proteins to signal allelic exclusion.

PMID- 12220935
TI  - The transient expression of pre-B cell receptors governs B cell development.
AB  - Only a subpopulation of relatively large pre-B cells express pre-B cell receptors
      (preBCR) that can be seen with very sensitive immunofluorescence methods.
      Inefficient assembly of the multicomponent preBCR coupled with their ligand
      induced endocytosis may account for the remarkably low in vivo levels of preBCR
      expression. Signaling initiated via the preBCR promotes cellular proliferation
      and RAG-1 and RAG-2 downregulation to interrupt the immunoglobulin V(D)J gene
      rearrangement process. Silencing of the surrogate light chain genes, VpreB and
      lambda5, then terminates preBCR expression to permit cell cycle exit, recombinase
      gene upregulation, and VJ(L) rearrangement by small pre-B cells destined to
      become B cells.

PMID- 12220938
TI  - COPD: clinical phenotypes.
AB  - Different phenotypic presentations in advanced stages of COPD are less common
      than in years past because of therapies that alter the manifestations of disease.
      Early stages of COPD are often asymptotic, but may present as asthma, chronic
      bronchitis, emphysema or combinations. Unusual presentations at young age are not
      common, but may be dramatic.

PMID- 12220936
TI  - Cell surface immunoglobulin receptors in B cell development.
AB  - Expression of surface immunoglobulin (sIg) related receptors has been conserved
      in phylogenetically distinct species as a critical checkpoint in B cell
      development. The sIg receptor comprises extracellular IgM heavy and light chains,
      with the potential for ligand binding, complexed to the Igalpha/Igbeta
      heterodimer that is responsible for signal transduction through sIg. Experimental
      systems, from both avian and murine models of B cell development, have been
      designed to identify the function of individual receptor components in B cell
      development. In this review, we assess the regulatory functions of different
      components of the sIg receptor complex during early development in experimental
      systems from evolutionarily distinct species.

PMID- 12220939
TI  - Global Initiative for Chronic Obstructive Lung Diseases (GOLD).
AB  - Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic
      morbidity and mortality throughout the world. In an effort to increase awareness
      of COPD and to develop consensus on scientific evidence for management and
      prevention of this disease, the Global Initiative for Chronic Obstructive Lung
      Disease (GOLD) program was formed. A summary of the GOLD program is presented
      along with information about GOLD documents.

PMID- 12220941
TI  - Effects of inhaled furosemide on CO(2) ventilatory responsiveness in humans.
AB  - We previously showed that inhaled furosemide improves experimentally induced
      dyspnea. In order to test the possibility that inhaled furosemide may alter the
      CO(2) chemosensitivity and thereby reduce the dyspneic sensation, the effect of
      inhaled furosemide on CO(2) chemosensitivity was evaluated with a double-blinded,
      randomized crossover design in 10 healthy subjects. The CO(2) chemosensitivity
      was measured by the steady-state and rebreathing methods before and after the
      inhalation of placebo (normal saline) and furosemide aerosols (40 mg). In
      addition, subjects were asked to rate their sensation of respiratory discomfort
      using a visual analog scale (dyspneic VAS) during the measurement of CO(2)
      chemosensitivity with the steady-state method. Our results showed that (1)
      inhaled furosemide does not affect the breathing patterns of resting breathing,
      (2) inhaled furosemide does not affect the slope and intercept of the CO(2)
      response curve, regardless of whether the CO(2) chemosensitivity is measured by
      the steady-state technique or rebreathing technique and (3) inhaled furosemide
      improves the dyspneic sensation produced during hypercapnic hyperpnea. These
      results suggest that the mechanism of the improvement of dyspnea by inhaling
      furosemide is not associated with the decrease in the ventilatory drive to CO(2).

PMID- 12220940
TI  - The protective role of epithelium-derived nitric oxide in isolated bovine
      trachea.
AB  - Airway epithelial cells from bovine airways can release relaxant factors such as
      nitric oxide (NO) and prostaglandin E(2) and the removal of airway epithelium
      results in an increased responsiveness of smooth muscle to spasmogen stimuli. In
      this study, we assessed whether or not epithelial NO modulates the contractile
      response of bovine trachea in vitro.Cumulative concentration-response curves to
      acetylcholine (ACh), histamine (Hist) and 5-hydroxytryptamine (5-HT) were
      obtained in both intact and epithelium denuded tracheal strips in the presence of
      indomethacin (10 microM).In intact, but not in epithelium denuded strips,
      preincubation with the NO synthase inhibitor L-N((G))-Nitro-arginine methyl ester
      (L-NAME), but not with D-NAME, shifted to the left the concentration-response
      curve to ACh (pD(2) values in the absence and in the presence of L-NAME were
      3.47+/-0.1 and 4.60+/-0.1, respectively; P<0.05) and to Hist (pD(2) in the
      absence and in the presence of L-NAME: 3.89+/-0.1 and 4.54+/-0.1, respectively;
      P<0.05). This effect was reversed by L-arginine (1mM), but not by D-arginine. The
      contractile response to 5-HT was not affected by L-NAME in either intact or
      epithelium denuded strips. These data suggest that NO is an epithelial relaxant
      factor modulating airway cholinergic and histaminergic contraction of bovine
      trachea and that the activation of the epithelial NO synthase is a mediator
      specific process.

PMID- 12220942
TI  - Single-dose comparison of formoterol (Oxis) Turbuhaler 6 microg and formoterol
      Aerolizer 12 microg in moderate to severe asthma: a randomised, crossover study.
AB  - Formoterol inhaled via Turbuhaler (Oxis) or Aerolizer (Foradil) produces fast and
      long-lasting bronchodilation in asthmatic patients. While formoterol Turbuhaler
      provides sustained efficacy for > or =12h at a metered dose of 6 microg
      (delivered dose 4.5 microg), the recommended metered dose for formoterol
      Aerolizer is 12 microg (delivered dose unknown). This difference may be
      attributable to improved lung deposition with the Turbuhaler. This open,
      randomised, crossover study compared the effects of a single metered dose of
      formoterol Turbuhaler 6 microg and formoterol Aerolizer 12 microg in 16 patients
      with stable moderate-to-severe asthma. Pulmonary function, assessed by measuring
      specific airway conductance (sGaw), was determined at intervals of < or =8h post
      inhalation of each drug on separate study days. Both inhalers increased sGaw at
      all time points. There were no significant differences between the two
      formulations in onset of activity, maximum effect, duration of effect or area
      under the response curve. Furthermore, both treatments were well tolerated with
      no differences in adverse events, blood pressure or heart rate; thus the
      formoterol Turbuhaler may, therefore, have an improved therapeutic index. This
      pilot study indicates that the same clinical effect can be achieved with half the
      metered dose (6 microg) of formoterol Turbuhaler compared with formoterol
      Aerolizer (12 microg).

PMID- 12220943
TI  - Relaxant effect of oxygen free radicals on rabbit tracheal smooth muscle.
AB  - We investigated the effect of exogenously generated superoxide anions (O(2)(-)),
      hydrogen peroxide (H(2)O(2)) and hydroxyl radicals (.OH) on isolated rabbit
      tracheal smooth muscle suspended in Krebs-Ringer solution. The ability of oxygen
      free radicals (OFRs) to affect acetyicholine (Ach)-induced contraction in these
      muscles was also investigated. OFRs, in general, produced a concentration
      dependent relaxation of the tracheal smooth muscle in the doses used. However, in
      large concentrations, O(2)(-) and H(2)O(2) produced effects which were smaller
      than those obtained with lower concentrations. The relaxant effects of these
      oxyradicals were progressive and lasted throughout the 20min observation period.
      At all concentrations used, the OFRs tended to abolish or reduce Ach-induced
      contraction in a concentration-dependent manner. O(2)(-) was more potent than
      H(2)O(2) or DHF in relaxing the Ach-precontracted muscle and in inhibiting the
      response of the muscle to Ach. OFR-induced relaxation of the Ach-contracted
      muscle was not due to inactivation of the Ach by OFRs. Relaxation produced by
      OFRs was greater in preparations with intact epithelium than in those denuded of
      epithelium. The relaxant effects were blocked by indomethacin, a cyclooxygenase
      inhibitor. OFRs in the presence of indomethacin produced contraction only in the
      preparations with intact epithelium, suggesting a release of contractile
      factor(s) from epithelium. These results suggest that OFRs relax rabbit tracheal
      smooth muscle. The relaxation appears to be mediated through the synthesis and
      release of prostaglandins from the epithelium and smooth muscles.

PMID- 12220944
TI  - N-acetylcysteine effect on the luminol-dependent chemiluminescence pattern of
      reactive oxygen species generation by human polymorphonuclear leukocytes.
AB  - The evidence of the effect of N-acetylcysteine on reactive oxygen species
      produced by human polymorphonuclear leukocytes (PMNs) is often contradictory, as
      thiol compounds may react with not only reactive oxygen and nitrogen species but
      also they may influence intracellular glutathione levels. The effect of 20, 100
      and 200 microM N-aceylcysteine (NAC) on luminol dependent chemiluminescence
      (LDCL) of human PMNs (10(6) cells/ml phospate buffered saline (PBS)) and whole
      blood to N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol-12-myristate
      13-acetate (PMA) was studied. Further, the ability of NAC to increase PMNs
      intracellular thiols and affect subsequent PMNs, stimulation was assessed. NAC
      100 and 200 microM, but not 20 microM, was found to attenuate the kinetic
      parameters of initial phase of fMLP-stimulated PMNs oxidative burst. NAC at the
      concentration of 100 and 200 microM decreased the rate, maximum and integrated
      value of PMNs response to fMLP. The integrated value of PMA-induced PMNs and fMLP
      induced whole blood LDCL response was also decreased by 100 and 200 microM NAC.
      Furthermore, all tested NAC concentrations decreased LDCL of resting PMNs
      suspension. The chemiluminescence pattern of reactive oxygen species (ROS)
      generation by PMNs stimulated with fMLP or PMA did not differ significantly from
      those preincubated with either 20, 100, or 200 microM NAC. Similarly, NAC did not
      increase the concentration of intracellular thiols in resting PMNs. However,
      addition of 200 microM NAC to PMA-stimulated PMNs prevented the decline in
      intracellular thiols pool. Both PMA- and fMLP-activated PMNs oxidized
      extracellular NAC. These results indicate that NAC decreases the intensity of
      PMNs oxidative burst by direct scavenger activity.

PMID- 12220945
TI  - Occurrence of dopaminergic (D(2)) receptors within the rabbit pulmonary
      circulation.
AB  - The pharmacological characteristics and the microanatomical localization of
      dopamine D(2)-like receptors, or more correctly spiroperidol binding sites, in
      the rabbit pulmonary circulation were studied using combined marker binding and
      light microscopy autoradiography with [((3))H]-spiroperidol (spiperone) as
      marker. The marker was bound to the samples of the pulmonary artery in a manner
      consistent with the labelling of dopamine D(2)-like receptors with an equilibrium
      dissociation constant (K(d)) of about 2.4+/-0.07 nmol/l and a maximum density of
      binding sites of 65+/-4.5 fmol/mg tissue. Samples of bronchial artery show the
      same results as those of the pulmonary artery. In contrast, binding experiments
      made with samples of rabbit lung (capillary of the microcirculation), of
      pulmonary veins and/or of bronchial veins did not allow the evaluation of
      specific binding.Autoradiography, observed with light microscopy, showed the
      development of specific silver grains within the whole wall of extraparenchymal
      branches of the pulmonary artery and/or of the bronchial artery. Development of
      silver grains was inhibited by compounds active on the dopamine receptors. The
      greater sensitivity to displacement by domperidone, haloperidol, and
      bromocriptine than to displacement by N-propyl-nor-apomorphine, quinpirole and
      clozapine suggests that the binding sites observed in extraparenchymal, large and
      medium-sized branches of the rabbit pulmonary and bronchial arteries belong,
      likely, to the dopamine D(2) receptor subtype. Quantitative analysis of images
      let us count the amount of these receptors in many samples of the pulmonary
      and/or bronchial arteries.

PMID- 12220946
TI  - Actions other than smooth muscle relaxation may play a role in the protective
      effects of formoterol on the allergen-induced late asthmatic reaction.
AB  - Long-acting beta(2)-adrenoceptor agonists attenuate the allergen-induced late
      asthmatic reaction. We evaluated whether other mechanisms in addition to airway
      smooth muscle relaxation may be implicated in this protective effect. The effects
      of formoterol (Foradil Aerolizer(TM), 24 microg dry powder) on the late asthmatic
      reaction were assessed by a randomised crossover factorial study in 24 patients
      with asthma. Four challenge/treatment combinations were tested: (A)
      saline/placebo, (B) saline/formoterol, (C) allergen/placebo, (D)
      allergen/formoterol. Formoterol and placebo were administered double blind after
      the last inhalation of the allergen or saline. FEV(1) was measured up to 32 h.
      The bronchodilator effect of formoterol was estimated as (B-A) and the overall
      protective effect as (D-C). The effect not due to bronchodilation was estimated
      as [(D-C)-(B-A)]/2. The bronchodilator effect of formoterol was statistically
      significant up to 5h (all P< or =0.015). Formoterol significantly attenuated the
      late asthmatic reaction between 3 and 32 h after allergen inhalation (all P< or
      =0.0012). The difference between this protective effect and the bronchodilator
      effect was statistically significant at 5 h and between 7 and 28 h after allergen
      inhalation (all P< or =0.035). Our results suggest that functional antagonism may
      not be the sole mechanism by which formoterol attenuates the allergen-induced
      late asthmatic reaction.

PMID- 12220947
TI  - Effects of chronic treatment with cromakalim and glibenclamide in alloxan-induced
      diabetic rats.
AB  - We have studied the effects of chronic treatment with cromakalim (75 ug kg(-1)
      per day) and glibenclamide (20 mg kg(-1) per day) in alloxan-induced diabetic
      rats. Injection of alloxan (60 mg kg(-1)/i.v., single dose) produced a
      significant increase in the blood pressure, bradycardia, hyperglycemia,
      hypoinsulinemia, hyperlipidemia, hypothyroidism and depression in left
      ventricular developed pressure (LVDP). While glibenclamide significantly
      prevented alloxan-induced hyperglycemia and hypoinsulinaemia, it failed to alter
      hypertension, bradycardia, hypertriglyceridaemia and hypercholesterolemia.
      Treatment with cromakalim-prevented hypertension and bradycardia, but not the
      hyperglycemia or hypoinsulinaemia. Co-administration of cromakalim with
      glibenclamide antagonized the effect of glibenclamide on these parameters.
      Cromakalim treatment also prevented alloxan-induced hypercholesterolemia and
      hypertriglyceridaemia. It also produced a significant increase in serum T(3) and
      T(4) levels. Glibenclamide did not significantly alter alloxan-induced
      hypothyroidism. In conclusion our data suggest that cromakalim and glibenclamide
      produce some metabolic effects that are either not related to K(ATP) channel
      modulation or may involve different sub-types of potassium channels. Further
      glibenclamide when combined with cromakalim may not be beneficial in a condition
      when diabetes mellitus and hypertension co-exits.

PMID- 12220948
TI  - Verification of protector effect of the norepinephrine and felypressin upon the
      cardiovascular system under action of the lidocaine hydrochloride and prilocaine
      hydrochloride in anesthetized rats.
AB  - Vasoconstrictor substances, as norepinephrine and epinephrine, were mixtured to
      local anesthetics to decrease their toxic effects and to prolong the depth of the
      anesthesia. However, these catecholamines produce systolic and diastolic
      hypertension. The effects of felypressin, a synthetic vasoconstrictor, upon
      arterial blood pressure and heart are lesser than those of norepinephrine or
      epinephrine, but due to its effects like oxytocin these catecholamines are yet
      the most used vasoconstrictors in association with lidocaine or another
      anesthetic salt. These vasoconstrictors are contraindicated for some physician,
      mainly for cardiac patients. But, are the catecholamines or is the salt the most
      dangerous components of the local anesthetic? The effects of the salt and
      catecholamines are opposite, but which of these exercises their effects first
      when inside blood vessel? Singi et al. [Pharmacol. Res. 44 (2001)] demonstrated
      that the first effect is always of the salt and that norepinephrine promotes
      protector effects upon guinea-pig isolated heart against lidocaine action. But,
      is this true for in vivo animals? The present study was performed with the aiming
      to answer this question and to verify if felypressin can induce the same effect
      of the norepinephrine. Fourteen Rattus norvegicus albinus, weighing 350g on
      average, were used. After being anesthetized with sodic thiopental, they were
      tracheostomizeds and one jugular and one carotid were cannuled for application of
      substances and to record the blood arterial pressure, respectively. The ECG was
      gotten through electrodes located in the front and back paws of the animals. The
      animals were separated in two groups, each one with seven rats. The lidocaine
      hydrochloride 2% in the doses of 600 microg and 3% in the doses of 900 microg
      acted on the cardiovascular system reducing the arterial pressure and modifying
      the electrocardiogram, while the prilocaine hydrochloride, in the same doses,
      also reduced the arterial pressure, but did not modify the electrocardiogram.
      When norepinephrine was associated to lidocaine 3% hydrochloride, it was possible
      to observe that this salt always exercised its effect first and a protective
      effect against the fall of pressure produced for the lidocaine. The same
      protective effect did not occur when felypressin was associated with prilocaine
      hydrochloride 3%.

PMID- 12220949
TI  - Cytoskeleton, passive tension and the contraction of the rat aorta to phorbol
      12,13-dibutyrate.
AB  - The influence of passive tension on contractions to phorbol 12,13-dibutyrate (1
      microM PBDu) on the thoracic aorta of Wistar and SHR rats, aged 8-12 weeks, and
      the functional importance of both the actin and the tubulin components of the
      cytoskeleton, were studied. Contractile responses to PBDu (1 microM) were
      obtained in aorta rings, at two levels of passive tension: 3 and 0.5g. These
      responses were expressed as percentage of the maximal response to noradrenaline
      obtained in the beginning of the experiment at a tension of 2g. Responses to PBDu
      were significantly larger (P<0.05) at 3g than at 0.5g in both kinds of rats:
      226.5+/-34.4%, n=6, versus 143.0+/-28.5%, n=6, respectively, for SHR; 153.0+/
      12.9%, n=8, versus 109.0+/-7.3%, n=7, respectively, for Wistar rats. Responses to
      PBDu were markedly decreased by cytochalasin B (50 microM) (to 61.3+/-14.3%, n=6,
      at 3g, and 29.6+/-17.8%, n=5, at 0.5g in SHR; to 18.5+/-0.9%, n=6, at 3g, and
      6.4+/-1.8%, n=5, at 0.5g in Wistar rats). Colchicine (100 microM) failed to
      produce a decrease in responses to PBDu in both strains of rats. It is concluded
      that responses to phorbol ester action depend on passive tension. This difference
      may depend on filament interaction. Contractions to PBDu in the rat aorta may be
      highly dependent on actin polymerization.

PMID- 12220950
TI  - The role of poly(ADP-ribose) synthetase inhibition in preventing endotoxemia
      induced intestinal epithelial apoptosis.
AB  - In this lipopolysaccharide (LPS)-induced endotoxemia model, the effects of 3
      aminobenzamide (3-AB), a poly(ADP-ribose) synthetase (PARS) inhibitor, on ileal
      apoptosis were evaluated by light microscopy and M30 cell death staining.
      Moreover, the relationship between Bcl-2, iNOS expression, and serum nitrate
      (NO(3)(-)) levels were investigated. Thirty-two male Wistar rats, weighing 180
      220g were randomly divided into four groups. The group I (control; n=8) received
      saline and group II (sepsis; n=8) received 10 mg kg(-1) LPS intraperitoneally. 3
      AB was given to the group IV (S+3-AB; n=8) 20 min before giving LPS and to the
      group III (C+3-AB; n=8) 20 min before giving saline. Six hours later, blood and
      ileum samples were taken. Endotoxemic group exhibited significant apoptosis in
      intestinal epithelial cells and the immunohistochemical examination with M30 was
      demonstrated that the 3-AB reduced the LPS-induced intestinal apoptosis. Serum
      NO(3)(-) level was increased in endotoxemic group, whereas the elevation of
      NO(3)(-) level was prevented in LPS+3-AB group (P<0.05). The increased iNOS
      expression observed in the LPS group was also prevented by 3-AB. Compared with
      the endotoxemic group, ileal epithelial columnar cells from LPS+3-AB group had a
      dense Bcl-2 staining which was almost identical with control. In conclusion, 3-AB
      decreases LPS-induced apoptosis in ileum by preventing LPS-induced depletion of
      Bcl-2 and blocking iNOS gene. Modification of Bcl-2 expression by PARS inhibitors
      should further be investigated as a new therapeutic alternatives in septic
      states.

PMID- 12220951
TI  - Methodology for urinary 8-hydroxy-2'-deoxyguanosine analysis by HPLC with
      electrochemical detection.
AB  - The compound 8-hydroxy-2'-deoxyguanosine (8-OHdG), one of the major oxidative DNA
      base products, is a commonly used biomarker of oxidative DNA damage. The routine
      measurement of 8-OHdG in biologic samples, and especially in urine, is inherently
      a challenging analytical problem due to the low levels of the analyte and the
      complexity of the sample. In this study, a simple and rapid procedure based on
      one step solid phase extraction (SPE) followed by high-performance liquid
      chromatography with electrochemical detection (HPLC-ECD) analysis is described.
      The methodology proposed resulted in a recovery of 74.5+/-12% for urinary 8-OHdG
      with a detection limit of 5.0 microg l(-1).

PMID- 12220952
TI  - Protective effect of melatonin in carrageenan-induced acute local inflammation.
AB  - The aim of the present study was to investigate the protective effect of the
      pineal hormone melatonin in a model of acute local inflammation (carrageenan
      induced paw oedema). Inflammation was assessed by measurement of nitric oxide
      (NO), Malondialdehyde (MDA) and glutathione levels in the paw tissue in rats. The
      intraplantar injection of carrageenan elicited an inflammatory response that was
      characterised by a time-dependent increase in paw oedema, increased level of
      nitrite/nitrate and MDA, a lipid peroxidation product and decreased glutathione
      levels in the paw tissue. The maximal increase in paw volume was observed at 4h
      after administration (maximal in paw volume 160+/-3.34 ml). In addition, NO level
      and MDA were markedly increased in the carrageenan-treated paw (59.96+/-6.58 and
      19.33+/-3.35 micromol g(-1), respectively), versus in the control paw glutathione
      level decreased in paw tissue (3.24+/-0.24 micromol g(-1)). However, carrageenan
      induced paw oedema was significantly reduced in a dose-dependent manner by
      treatment with melatonin (given at 5 and 10 mg kg(-1)) at 1, 2, 3, 4, 5 and 6h
      after injection of carrageenan. Melatonin treatment also caused a significant
      reduction of the NO and MDA levels, while increasing glutathione level in the paw
      tissue. Our findings support the view that melatonin exerts anti-inflammatory
      effects. Part of these anti-inflammatory effect may be related to an inhibition
      of the NO and MDA production, while another part may be related to increase of
      the glutathione level in the paw tissue.

PMID- 12220953
TI  - Effects of paracetamol and propacetamol on gastric mucosal damage and gastric
      lipid peroxidation caused by acetylsalicylic acid (ASA) in rats.
AB  - We have studied the effect of paracetamol and its pro-drug propacetamol on
      gastric mucosal damage induced by acetylsalicylic acid (ASA) and its possible
      relation to changes in gastric lipid peroxidation status in rats. Paracetamol or
      propacetamol were administered intragastrically 1h before ASA (300 mg kg(-1)) in
      the following equivalent doses: 62.5, 125.0 and 250.0 mg kg(-1) or 125.0, 250.0
      and 500.0 mg kg(-1), respectively. The effects of the tested agents were compared
      to that of prostaglandin E2 (PGE2) 15, 30 and 60 mg kg(-1). Gastric ulcer
      formation was estimated morphometrically 4h after ASA administration.
      Malondialdehyde (MDA), glutathione (reduced, GSH, and oxidized, GSSG) and uric
      acid (UA) were determined in gastric mucosa and blood plasma and used as
      biochemical markers of the oxidative status. The results showed that paracetamol
      (250, 125, 62.5 mg kg(-1)) and propacetamol (500, 250, 125 mg kg(-1)) diminished
      the area of ASA-induced gastric lesions. The effect of propacetamol was more
      pronounced than that of paracetamol and similar to that of PGE2. Gastric MDA
      increased 3-fold in the ASA-group. The tested agents reduced it by a range of 30
      70%. In all pretreated groups gastric glutathione and UA levels were found higher
      than that of control group and lower than that of ASA-group. Paracetamol and
      propacetamol, as well as PGE2, diminished the lipid peroxidation in plasma to a
      lesser extent than in gastric mucosa, but maintained elevated levels of the
      selective plasma antioxidant UA. These results show that the ASA-induced gastric
      mucosal damage is accompanied by the development of oxidative stress, evidenced
      by the accumulation of MDA, and concomitant initial activation of cell
      antioxidant defences. As paracetamol and propacetamol tend to decrease gastric
      lesions caused by ASA and alter gastric mucosal MDA, glutathione and UA values in
      a favorable manner, it could be suggested that their effects on the gastric
      mucosa could be related to interference with oxidative stress development.

PMID- 12220954
TI  - Gaba-benzodiazepine receptor complex in brain oxidative metabolism regulation.
AB  - This study investigated the impact of modulating the gamma-aminobutyric acid(A)
      (GABA)(A)-benzodiazepine receptor complex activity on the rat frontal cortex
      slices oxygen consumption (QO(2)), polarographically determined using the
      biological oxygen monitor. Throughout the study, diazepam, flumazenil and
      picrotoxin were administered i.p. 30 min before sacrificing animals and obtaining
      slice preparations, while GABA was added directly into the medium in the reaction
      chamber. GABA decreased QO(2) in concentrations of 5 x 10(-4), 10(-2) and 5 x 10(
      2)mol l(-1), while 10(-5) and 10(-6)mol l(-1) GABA had no effect, as well as
      diazepam, flumazenil and picrotoxin. All diazepam doses (1, 2.5 and 5 mg kg(-1))
      increased action of 5 x 10(-4)mol l(-1) GABA, whereas 2.5 mg kg(-1) dose
      amplified the effect of 10(-6)mol l(-1) GABA. Flumazenil and picrotoxin (5 mg kg(
      1) both) blocked diazepam's effects. Flumazenil augmented 10(-6)mol l(-1) GABA
      effects, while picrotoxin and flumazenil abolished the effects of 5 x 10(-4)mol
      l(-1) GABA. To our knowledge, this is the first study to examine the influence of
      modulation of GABA(A)-benzodiazepine receptor function on cerebral metabolism of
      oxygen in in vitro settings. The results are in accordance with those obtained in
      numerous in vivo studies, pointing to the moderate level of influence of GABA(A)
      benzodiazepine receptor complex on QO(2) regulation.

PMID- 12220955
TI  - In vivo glioma growth requires host-derived matrix metalloproteinase 2 for
      maintenance of angioarchitecture.
AB  - Glioma, the most common form of brain tumor, has been shown mostly by in vitro
      studies to utilize matrix metalloproteinase (MMP) for invasive growth through
      degradation of the extracellular matrix. In order to examine the in vivo role of
      MMP, we established a rodent model of glioma progression using C6 rat glioma
      cells and analyzed the effect of tissue inhibitors of metalloproteinases (TIMPs).
      TIMP-2 rather than TIMP-1 caused significant reduction of the tumor size
      accompanied by the presence of degenerated blood vessels and ischemic necrosis.
      Because TIMP-2 inhibits MMP-2 preferentially, we then examined glioma growth in
      MMP-2-deficient mice and observed essentially identical consequences. While MMP-2
      activity was present in the tumor and adjacent tissues of the wild-type mice, no
      MMP-2 activity was detected even in the tumor of the null mice, although C6 cells
      are known to express MMP-2. These observations suggest that glioma induces MMP-2
      and utilizes its activity in the host tissue to support angiogenesis and to
      maintain angioarchitecture.

PMID- 12220956
TI  - Effects of (-)deprenyl (selegiline) on acetylcholinesterase and Na(+),K(+)-ATPase
      activities in adult rat whole brain.
AB  - (-)Deprenyl is an irreversible inhibitor of monoaminoxidase-B (MAO-B) at
      concentration 10(-6)M and of both MAO-A and MAO-B at concentration 10(-5)M. In
      this study, the effect of different concentrations (10(-7)-10(-4)M) of (
      )deprenyl on the activity of acetylcholinesterase (AChE), Na(+),K(+)-ATPase and
      Mg(2+)-ATPase was investigated in homogenates of adult rat whole brain and in
      pure enzymes. Drug preincubation period with the homogenates or pure enzymes was
      1 and 3h. Brain AChE activity was decreased by 30-39% (P<0.01) when exposed to
      10(-4)M (-)deprenyl, by 22-25% (P<0.01) when exposed to 10(-5)M of the drug, and
      by 18-20% (P<0.01) after preincubation with a concentration of the drug 10(-6)M.
      Brain Na(+),K(+)-ATPase was stimulated by 46-162% (P<0.001) when the homogenate
      was preincubated with 10(-4)M (-)deprenyl and by 36-104% (P<0.001) for
      preincubation with drug concentration 10(-6)M. No effect was observed on the
      activity of brain Mg(2+)-ATPase, pure AChE or pure Na(+),K(+)-ATPase when exposed
      to the above concentrations of the drug. We conclude that (-)deprenyl is an
      indirect AChE inhibitor and Na(+),K(+)-ATPase stimulator in the rat brain (in
      vitro).

PMID- 12220957
TI  - Selenium pretreatment prevents bacterial translocation in rat intestinal
      ischemia/reperfusion model.
AB  - Protective role of selenium against free radical damage was first demonstrated in
      the heart and this effect was further questioned in other systems. In the present
      study, the effects of exogenously administered selenium on intestinal fine
      morphology, lipid peroxidation, and bacterial translocation (BT) in experimental
      intestinal ischemia/reperfusion (I/R) model were examined. Thirty-two male Wistar
      rats weighing 250-300 g were randomized into four groups. Sham group (n=8)
      underwent laparotomy only. In the I/R group (n=8), laparotomy was performed and
      the superior mesenteric artery was occluded using an atraumatic microvascular
      clamp for 30 min. In corresponding selenium-treated groups (n=8 each), sodium
      selenate was given 0.2 mg kg(-1)day(-1) intraperitoneally (i.p.) for 3
      consecutive days, prior to surgery for either laparotomy only or with I/R. Twenty
      four hours later, tissue samples from liver, spleen, and mesenteric lymph nodes
      were obtained under sterile conditions for microbiological analysis and further
      evaluation of I/R-induced intestinal injury. Ileum samples were fixed in 10%
      formaldehyde for histopathological evaluation. In the I/R group, the incidence of
      bacteria-isolated mesenteric lymph nodes, spleen, and liver was significantly
      higher than other groups (P<0.05). Selenium supplementation prevented I/R-induced
      BT and significantly reduced the I/R-induced intestinal injury (P<0.05). Tissue
      MDA levels from the ileum specimens of selenium-treated rats were significantly
      lower than that of the I/R group (P<0.05). Our results provide evidence that the
      relationship between BT and lipid peroxidation in intestinal tissue is crucial.
      Selenium pretreatment reduces lipid peroxidation which contributes to the
      maintenance of intestinal mucosal integrity.

PMID- 12220958
TI  - Keratinocyte growth factor stimulates the migration and proliferation of breast
      cancer cells in a culture wounding model.
AB  - Growth factors are known to influence the progression, motility and invasiveness
      of tumor cells. In a previous study, we reported that conditioned media from NIH
      3T3 cells (mouse fibroblast), which contains KGF, increased the motile morphology
      of estrogen receptor (ER)-positive breast cancer cells and produced no effect on
      ER-negative cells. The present study examined the influence of human KGF on two
      estrogen receptor (ER)-positive human breast cancer cell lines (MCF-7 and T-47D)
      using a culture wounding model to evaluate cell proliferation and migration over
      a period of 48h. In the present study we observed that KGF enhanced the migration
      and proliferation of both MCF-7 and T-47D breast cancer cells. In both cell lines
      the response to KGF was found to be both dose- and time-dependent. However, the
      total migration and proliferation response of the MCF-7 cells to KGF was much
      greater than that observed in the T-47D cells. The results of this study
      demonstrate that human KGF enhances the migration and proliferation of human
      breast cancer cells. Further, these results support the concept that KGF may be
      an early signal in the progression of breast cancer to a more motile and
      metastatic phenotype.

PMID- 12220959
TI  - Anapsos (Polypodium leucotomos) modulates lymphoid cells and the expression of
      adhesion molecules.
AB  - Anapsos is a medical prescription registered in the Health Ministry of Spain,
      that is obtained from the rhizomes of the fern Polypodium leucotomos. An
      immunomodulating effect of Anapsos on certain lymphocyte subsets and cytokines
      has already been described in the literature. The current study extends and
      supports part of the aforementioned results of the product on the immune system,
      showing the ability of Anapsos to stimulate proliferation and activation of T and
      natural killer lymphocytes, as well as an important down-regulating effect on
      CD11, CD18 and CD62-L adhesion molecules, both on peripheral blood mononuclear
      cells and on U-937 and HL-60 cell lines.

PMID- 12220960
TI  - Biochemical and hematological side effects of clofazimine in leprosy patients.
AB  - Gastrointestinal toxicity and red skin discoloration were the major side effects
      observed in leprosy patients undergoing long-term treatment with clofazimine
      (CFZ). Hematological and biochemical alterations have been cited among other side
      effects; however, their real magnitude and clinical significance at the doses
      currently employed in therapy have not been sufficiently documented. We therefore
      investigated the correlation between CFZ plasma concentration and biochemical
      (transaminases, bilirubins, alkaline phosphatase, gamma-glutamyltransferase,
      amylase, urea, creatinine, and potassium plasma levels) as well as hematological
      changes blood and reticulocyte counts, osmotic fragility, detection of Heinz
      bodies and methemoglobinemia (MHM), following in two regimes of treatment: CFZ as
      a single drug and CFZ as part of multidrug (MDT) therapy, in combination with
      dapsone and rifampicin. MHM and hemolytic anemia were detected in the MDT group
      only. Eosinophilia was found in patients of either group. Determination of
      hepatic, pancreatic and renal biochemical parameters showed rare, occasional
      changes of apparently no clinical significance. We conclude that CFZ is a
      generally well tolerated and safe drug when given as a daily dose of 50mg, which
      is currently used in leprosy patients.

PMID- 12220961
TI  - Itraconazole solution: summary of pharmacokinetic features and review of activity
      in the treatment of fluconazole-resistant oral candidosis in HIV-infected
      persons.
AB  - The clinical pharmacology of itraconazole is presented in relation to its use in
      the treatment of fluconazole-resistant oropharyngeal candidosis. The oral
      solution is a new formulation of itraconazole in which itraconazole is
      solubilised with the use of cyclodextrin. This formulation has a higher
      bioavailability and leads to higher local concentrations in the oral cavity which
      are advantages over the solid capsule formulation. Literature, in which the use
      of itraconazole oral solution was described to treat fluconazole-resistant oral
      candidosis, is reviewed. In about 55% of the patients signs and symptoms of oral
      candidosis were resolved after treatment with itraconazole oral solution.
      Although all the reviewed studies lack data to objectively qualify all the
      included patients as having a fluconazole-resistant candidosis, the authors
      conclude, that based on the available information itraconazole oral solution 100
      or 200mg twice daily can be effective for fluconazole-resistant oropharyngeal
      candidosis (OPC) and should be considered prior to salvage therapy with
      intravenous amphotericin B. The use of itraconazole, however, requires careful
      monitoring of the patients co-medication for potential serious drug-drug
      interactions.

PMID- 12220962
TI  - Role of valsartan and other angiotensin receptor blocking agents in the
      management of cardiovascular disease.
AB  - Blockade of the renin-angiotensin system by angiotensin converting enzyme (ACE)
      inhibitors reduces mortality and morbidity in patients post-myocardial infarction
      as well as in chronic heart failure and hypertension. ACE inhibitors also have a
      well-established place in the treatment of diabetic nephropathy. Angiotensin
      receptor blockers (ARBs) have been developed to produce a more complete blockade
      of the actions of angiotensin II as compared to other drug classes, as well as an
      improved side effect profile. This article provides an overview of the place of
      ARBs in general and of the ARB valsartan in particular, and draws comparisons to
      ACE inhibitors in the treatment of cardiovascular diseases.

PMID- 12220963
TI  - Folic acid and vitamin B(12) supplementation attenuates isoprenaline-induced
      myocardial infarction in experimental hyperhomocysteinemic rats.
AB  - Hyperhomocysteinemia (Hhcy) is an independent risk factor for cardiovascular
      disease. Oxidative stress may contribute to the deleterious effects of
      homocysteine (Hcy). The aim of the present study is to study the effect of folic
      acid and Vitamin B(12) supplementation on isoprenaline (ISO)-induced myocardial
      infarction (MI) in hyperhomocysteinemic rats. Hhcy was induced by daily intake of
      methionine (1 g kg(-1) body weight) in the drinking water for 4 weeks. MI was
      then produced by a single subcutaneous injection of ISO (300 mg kg(-1), s.c.).
      Electrocardiographic parameters, heart rate, ST segment, and blood pressure as
      well as serum marker enzymes, creatine kinase (CK) and lactate dehydrogenase
      (LDH) were measured. Lipid peroxidation measured as malondialdehyde (MDA) and
      reduced glutathione (GSH) concentrations in heart tissue were estimated as
      indices of oxidative stress. Hhcy resulted in significant blood pressure
      reduction, ST segment elevation and increase in heart rate and serum CK and LDH
      levels. Cardiac MDA was significantly increased, while GSH was decreased in Hhcy
      group compared to the normal control group. All the measured parameters were
      greatly exaggerated in Hhcy rats treated with ISO in comparison with Hhcy rats
      alone. Administration of folic acid (10 mg kg(-1), orally via gavage) and Vitamin
      B(12) (500 microg kg(-1), i.m.) concurrently for 4 weeks during the induction of
      Hhcy markedly reduced the increase in heart rate, ST segment elevation and blood
      pressure reduction as well as the increase in serum CK and LDH levels. Cardiac
      MDA content was decreased while cardiac GSH was elevated in the treated group
      compared to Hhcy + ISO group. Moreover, the severe cardiac histopathological
      changes observed in Hhcy + ISO group were attenuated by folic acid and Vitamin
      B(12). These results suggest that Hhcy aggravates MI via oxidative stress
      mechanisms and that lowering Hcy level with folic acid and Vitamin B(12) can
      ameliorate the detrimental effects of Hhcy and may reduce the risk of MI.

PMID- 12220964
TI  - Hepatoprotective effects of 18beta-glycyrrhetinic acid on carbon tetrachloride
      induced liver injury: inhibition of cytochrome P450 2E1 expression.
AB  - The protective effects of 18beta-glycyrrhetinic acid (GA), the aglycone of
      glycyrrhizin (GL) derived from licorice, on carbon tetrachloride-induced
      hepatotoxicity and the possible mechanisms involved in this protection were
      investigated in mice. Pretreatment with GA prior to the administration of carbon
      tetrachloride significantly prevented an increase in serum alanine, aspartate
      aminotransferase activity and hepatic lipid peroxidation in a dose-dependent
      manner. In addition, pretreatment with GA also significantly prevented the
      depletion of glutathione (GSH) content in the livers of carbon tetrachloride
      intoxicated mice. However, reduced hepatic GSH levels and glutathione-S
      transferase activities were unaffected by treatment with GA alone. Carbon
      tetrachloride-induced hepatotoxicity was also prevented, as indicated by a liver
      histopathologic study. The effects of GA on the cytochrome P450 (P450) 2E1, the
      major isozyme involved in carbon tetrachloride bioactivation, were also
      investigated. Treatment of mice with GA resulted in a significant decrease of the
      P450 2E1-dependent hydroxylation of p-nitrophenol and aniline in a dose-dependent
      manner. Consistent with these observations, the P450 2E1 expressions were also
      decreased, as determined by immunoblot analysis. GA also showed antioxidant
      effects upon FeCl(2)-ascorbate-induced lipid peroxidation in mice liver
      homogenate and upon superoxide radical scavenging activity. These results show
      that protective effects of GA against the carbon tetrachloride-induced
      hepatotoxicity may be due to its ability to block the bioactivation of carbon
      tetrachloride, primarily by inhibiting the expression and activity of P450 2E1,
      and its free radical scavenging effects.

PMID- 12220965
TI  - The role of sodium cromolyn in treatment of paraquat-induced pulmonary fibrosis
      in rat.
AB  - Paraquat is a non-selective herbicide which is widely used in agriculture. It has
      potential of producing pulmonary fibrosis. In this study the therapeutic effect
      of different doses of sodium cromolyn on the development of paraquat-induced
      pulmonary fibrosis was investigated. In order to produce lung fibrosis, rats were
      given single oral dose of paraquat (40 mg kg(-1)). Two groups of animals were
      nebulised with 6 or 8 mg day(-1) cromolyn (divided into two doses per day) 5 days
      prior and 2 weeks after paraquat treatment. Control animals were given equivalent
      volume of normal saline and treated with cromolyn similar to the test groups.
      Rats were killed at the end of treatment course and lung tissues were tested
      histologically and biochemically. Histological examination of paraquat-treated
      animals showed marked infiltration of inflammatory cells in the alveolar spaces,
      septal thickening and fibrosis. Lesions were evident in many places of sections.
      Sodium cromolyn could markedly reduce such damages in lung tissue. Lung weight,
      hydroxyproline and collagen content of lung tissues were elevated significantly
      (P < 0.05) in paraquat group compared with control group. In cromolyn-treated
      groups such factors were near to control value and were significantly lower than
      paraquat group (P < 0.05). Results of this study indicate that sodium cromolyn
      can decrease the fibrogenic effect of paraquat on lung. Such effect may be due to
      the stabilising of mast cells and inhibition of inflammatory mediators by sodium
      cromolyn.

PMID- 12220966
TI  - Studies on the anti-inflammatory and anti-nociceptive effects of melatonin in the
      rat.
AB  - The present study aimed to evaluate the anti-inflammatory and anti-nociceptive
      effects of melatonin in the rat. Acute inflammation was induced by sub-plantar
      injection of carrageenan (1%) in the rat hind paw. The rats received vehicle or
      drug 30 min before carrageenan administration and were evaluated for paw oedema
      at 1, 2, 3, and 4 h post-carrageenan. The induced inflammation and the formation
      of oedema were determined by measurement of the paw thickness. Nociception was
      tested by determining vocalization following electrical stimulation of the tail.
      Given intraperitoneally (i.p.) 30 min before carrageenan, melatonin caused
      significant and a dose-dependent reduction of hind paw swelling induced by
      carrageenan. At doses of 0.5 and 1 mg kg(-1), melatonin inhibited the carrageenan
      induced oedema by 20.5 and 29.6% versus control values at 4 h post-carrageenan,
      respectively. Melatonin (0.5 and 1 mg kg(-1), i.p.) 30 min beforehand displayed
      anti-nociceptive effect in the electric stimulation of the rat tail test,
      increasing nociceptive thresholds to electrically-induced pain at 4 h post
      treatment by 29.6 and 39.5%, respectively. Melatonin given simultaneously with
      the non-selective COX-1 and COX-2 inhibitor indomethacin (5 mg kg(-1), i.p.) 30
      min prior to carrageenan, enhanced the anti-inflammatory effect of the latter in
      the carrageenan-induced paw oedema model by 23%. Melatonin (0.5 mg kg(-1), i.p.)
      increased the anti-nociceptive effect of indomethacin (5 mg kg(-1), i.p.).
      Meanwhile, the anti-inflammatory and anti-nociceptive effect of the highly
      selective COX-2 inhibitor rofecoxib (2.25 mg kg(-1), i.p.) was only slightly
      increased by melatonin administration at 0.5 mg kg(-1). Melatonin enhanced the
      anti-inflammatory effect of cysteamine (300 mg kg(-1), s.c.) in the carrageenan
      induced paw oedema. Melatonin (20 and 40 microg per paw) given prior to
      carrageenan into the rat hind paw was devoid of anti-inflammatory effect. These
      results indicate that melatonin possesses anti-inflammatory and anti-nociceptive
      properties in the rat and enhance those of indomethacin. This effect is likely to
      be centrally mediated.

PMID- 12220967
TI  - Indomethacin, caffeine and prochlorperazine alone and combined revert
      hyperalgesia in in vivo models of migraine.
AB  - The combination of indomethacin, caffeine, and prochlorperazine (hereinafter
      IndoProCaf) represents an effective antimigraine drug available on the Italian
      market. The aim of this study was to test the efficacy of the three active
      principles alone and in combination in reverting hyperalgesia. Hyperalgesia was
      induced by morphine withdrawal in mice treated with morphine for 15 days and then
      made hyperalgic by morphine substitution with water. This study showed that
      indomethacin 0.3 mg kg(-1), i.p.; caffeine 0.1 and 0.3 mg kg(-1), i.p.; and
      prochlorperazine 0.1 mg kg(-1), i.p.; as well as the combination of the three
      active principles, were able to revert morphine withdrawal induced hyperalgesia,
      causing a statistically significant increase of pain threshold in hyperalgic
      mice. In a second model, hyperalgesia was induced by the i.p. injection of a 0.3%
      solution of acetic acid in mice and was evaluated counting the number of
      abdominal constrictions. Indomethacin (0.1 mg kg(-1), i.p.), caffeine (0.3 mg kg(
      1), i.p.), and prochlorperazine (0.1 mg kg(-1), i.p.) reduced the number of
      abdominal constrictions, while the combination of the three active principles was
      able to abolish almost completely the abdominal constrictions, with a
      significantly higher efficacy compared to the single active principles. In both
      models, indomethacin, caffeine, and prochlorperazine reverted hyperalgesia at
      dosages 10 times lower than the corresponding analgesic ones. These data provide
      the pharmacologic evidence of the efficacy of IndoProCaf in reverting
      hyperalgesia, a condition of reduction of pain threshold similar to that
      occurring in migraine.

PMID- 12220968
TI  - Hypolipidemic effect of Cuminum cyminum L. on alloxan-induced diabetic rats.
AB  - Hyperlipidemia is an associated complication of diabetes mellitus. Many spices
      and herbs are known to be hypoglycaemic. Cuminum cyminum belonging to the family
      Apiaceae is widely used in Ayurvedic medicine for the treatment of dyspepsia,
      diarrhoea and jaundice. The present work was done to study the role of C. cyminum
      supplementation on the plasma and tissue lipids in alloxan diabetic rats. Oral
      administration of 0.25 g kg(-1) body weight of C. cyminum for 6 weeks to diabetic
      rats resulted in significant reduction in blood glucose and an increase in total
      haemoglobin and glycosylated haemoglobin. It also prevented a decrease in body
      weight. C. cyminum treatment also resulted in a significant reduction in plasma
      and tissue cholesterol, phospholipids, free fatty acids and triglycerides.
      Histological observations demonstrated significant fatty changes and inflammatory
      cell infiltrates in diabetic rat pancreas. But supplementation with C. cyminum to
      diabetic rats significantly reduced the fatty changes and inflammatory cell
      infiltrates. Moreover, C. cyminum supplementation was found to be more effective
      than glibenclamide in the treatment of diabetes mellitus.

PMID- 12220969
TI  - Comparative effects of curcumin and photo-irradiated curcumin on alcohol- and
      polyunsaturated fatty acid-induced hyperlipidemia.
AB  - It is a known fact that ethanol increases lipid levels in humans and experimental
      animals. Reports show that the increased intake of polyunsaturated fatty acids
      (PUFAs) along with alcohol produces various pathological changes in liver
      resulting in hyperlipidemia. Heating of oil rich in PUFA produces various lipid
      peroxidative end products, which aggravate the pathological changes. In the
      present study, we have investigated the effect of curcumin (C) and photo
      irradiated curcumin (IC) on alcohol- and PUFA-induced hyperlipidemia. Our results
      showed that the activities of alkaline phosphatase (ALP), gamma-glutamyl
      transferase (GGT) in plasma and levels of cholesterol, triglycerides (TGs) and
      free fatty acids (FFAs) in tissues were increased significantly in both alcohol +
      raw as well as heated PUFA groups compared to normal, but decreased significantly
      on treatment with curcumin and IC. The IC treatment decreased the levels more
      significantly compared to curcumin. The phospholipids (PLs) were increased
      significantly in heart and intestine and decreased in liver and kidney in both
      alcohol + raw as well as heated PUFA groups. The levels were significantly
      decreased in liver and kidney and increased in intestine and heart in both
      curcumin- and IC-treated groups. But the effect of IC was more pronounced than
      curcumin. Histopathological observations were also in correlation with the
      biochemical parameters. Thus, photo-irradiated curcumin proves itself to be more
      effective than curcumin in treating the above pathological conditions.

PMID- 12220970
TI  - The effects of dexamethasone on lipid peroxidation and nitric oxide levels on the
      healing of tracheal anastomoses: an experimental study in rats.
AB  - Corticosteroids are shown to have deleterious effects on wound healing for
      various tissues. Arginine metabolism and nitric oxide (NO) synthesis play an
      important role in many aspects of inflammation and wound healing. The study was
      designed to evaluate the relationship of dexamethasone impaired healing of
      tracheal anastomoses to NO metabolism and lipid peroxidation. Forty-two adult
      Wistar rats were randomly divided into five groups. The animals underwent
      tracheal transection and primary anastomoses. The groups were assigned as
      follows: Group I (GI) (sham, N = 6); Group II (GII) (control, N = 6); Group III
      (GIII), dexamethasone, 0.1 mg kg(-1) per day, intramuscularly for a week (N =
      10); Group IV (GIV), dexamethasone, 1 mg kg(-1) per day, intramuscularly for a
      week (N = 10); Group V (GV), dexamethasone, 6 mg kg(-1) intramuscularly as a
      single dose (N = 10). After 7 days, bursting pressure was used to evaluate
      anastomotic healing. Serum nitrite/nitrate and malondialdehyde (MDA) levels were
      measured as an index of NO synthesis and lipid peroxidation, respectively. The
      bursting pressure significantly decreased in GIII and GIV when compared to the
      control group. The difference between GIII and GIV was also statistically
      significant. Nitrite/nitrate and MDA levels of GIII were found to be
      significantly higher than the control group. Also, the difference was found to be
      statistically significant between GIII and GIV in regard to nitrite/nitrate
      levels. The present study demonstrates that daily administration of dexamethasone
      for a week inhibits NO synthesis in a dose-dependent manner on tracheal
      anastomotic healing. Besides the generally accepted evaluation parameters
      including bursting pressure and hydoxyproline content; NO and MDA levels may be
      helpful in the assessment of wound healing especially for the investigation of
      impairment mechanism.

PMID- 12220971
TI  - Protective effects of curcumin against ischaemia/reperfusion insult in rat
      forebrain.
AB  - Oxidative stress is believed to be implicated in the pathogenesis of
      postischaemic cerebral injury. Many antioxidants were shown to be neuroprotective
      in experimental models of cerebral ischaemia/reperfusion (I/R). The present study
      was designed to investigate the potential protective effects of curcumin (CUR)
      against I/R insult in rat forebrain. The model adopted was that of surgically
      induced forebrain ischaemia, performed by means of bilateral common carotid
      artery occlusion (BCCAO) for 1 h, followed by reperfusion for another 1h. The
      effects of a single i.p. dose of CUR (50, 100 or 200 mg kg(-1)), administered 0.5
      h after the onset of ischaemia, were investigated by assessing oxidative stress
      related biochemical parameters in rat forebrain. CUR, at the highest dose level
      (200 mg kg(-1)), decreased the I/R-induced elevated xanthine oxidase (XO)
      activity, superoxide anion (O(2)*(-)) production, malondialdehyde (MDA) level and
      glutathione peroxidase (GPx), superoxide dismutase (SOD), and lactate
      dehydrogenase (LDH) activities. On the other hand, CUR did not affect the
      declined reduced glutathione (GSH) content due to I/R insult. Worth mentioning is
      that the activity of catalase (CAT) did not change in response to either I/R
      insult or drug treatment. In conclusion, CUR was found to protect rat forebrain
      against I/R insult. These protective effects may be attributed to its antioxidant
      properties and/or its inhibitory effects on xanthine dehydrogenase/xanthine
      oxidase (XD/XO) conversion and resultant O(2)*(-) production.

PMID- 12220972
TI  - Baclofen analgesia: involvement of the GABAergic system.
AB  - The effect of baclofen, a GABA(B) agonist, has been studied in the hot plate test
      in mice, to analyze the possible involvement of the GABAergic system in baclofen
      analgesia. Baclofen (1-3 mg kg(-1) intraperitoneal (i.p.)) was found to elicit a
      dose-dependent antinociceptive effect. The antinociceptive effect of baclofen
      cannot be due to motor incoordination or sedation as the doses of baclofen which
      produce analgesia did not induce these effects during the rota-rod test. The
      antinociceptive effect of baclofen was reversed by 2-hydroxysaclofen, a GABA(B)
      antagonist by both systemic (3 mg kg(-1)) and intra cisterna magna
      (intracisternal (i.c.)) (0.3 mg kg(-1)) administration. The antagonist dose
      administered via i.c. produced a complete blockade and was 10-fold lower than the
      dose employed in i.p. administration. The data suggest that the antinociceptive
      effect of baclofen is GABA(B) receptor-mediated and reveal a central location of
      the analgesic effect of baclofen.

PMID- 12220973
TI  - Potential protective effect of melatonin against dibromoacetonitrile-induced
      oxidative stress in mouse stomach.
AB  - Dibromoacetonitrile (DBAN) is a disinfection by-product following chlorination of
      drinking water. Epidemiological studies indicate that it might present a
      potential hazard to human health. DBAN was previously found to induce oxidative
      stress in rat stomach as manifested by perturbation of some enzymatic and
      nonenzymatic antioxidant parameters. Therefore, we have investigated the
      oxidative stress possibly induced by DBAN in mouse stomach and possible
      protection by melatonin (MLT) as a free radical scavenger. In a dose-response
      study, mice were administered a single oral dose of DBAN (30, 60 and 120 mg kg(
      1)) and were sacrificed after 1 h. DBAN significantly reduced glutathione (GSH)
      content that was somehow dose-related, and inhibited glutathione-S-transferase
      (GST) activity in gastric tissues. The highest dose of DBAN (120 mg kg(-1))
      lowered GSH by 74% and induced a significant elevation of lipid peroxidation
      products, determined as thiobarbituric acid reactive substances (TBARS) by 69%.
      The same dose inhibited the gastric activities of GST, superoxide dismutase (SOD)
      and catalase (CAT) by 70, 57 and 23%, respectively. In a time-course study, mice
      were administered DBAN (60 mg kg(-1) p.o.) and sacrificed 0.5, 1, 3, 6, 12 and 24
      h after treatment. GSH was dramatically depleted at 0.5, 1, 3 and 6 h (45, 38, 39
      and 49% of control, respectively) and remained significantly low at 12 and 24 h.
      Also, DBAN caused an accumulation of TBARS in gastric tissues starting from 3 h
      and was maximum at 6 h (133% of the control). The enzymatic activities of GST and
      SOD were maximally inhibited by DBAN treatment at 0.5 h (32% for GST and 37% for
      SOD of the respective control). The activities of both enzymes returned to
      control values at 24 h. CAT activity was not affected by DBAN administration at
      all. Pretreatment of another group of mice with melatonin (10 mg kg(-1) per day
      p.o. 12 days) before administration of DBAN (60 mg kg(-1) p.o.) completely
      mitigated the aforementioned parameters. In conclusion, the present study
      indicates that DBAN induces a marked oxidative stress in mouse stomach as
      evidenced by GSH depletion, TBARS accumulation and GST, SOD and CAT inhibition.
      Melatonin could mitigate DBAN-induced oxidative stress in mouse stomach as it did
      almost normalize both the enzymatic and nonenzymatic antioxidant parameters.

PMID- 12220974
TI  - Hepatotoxicity following nevirapine-containing regimens in HIV-1-infected
      individuals.
AB  - To determine the incidence of hepatotoxicity and to investigate whether plasma
      concentrations of nevirapine, in addition to other risk factors, could predict
      hepatotoxicity during treatment with nevirapine-containing regimens, we conducted
      a retrospective analysis with data from 174 individuals infected with human
      immunodeficiency virus-1 (HIV-1). During regular visits to the clinic, blood
      samples were collected for the determination of nevirapine plasma concentrations
      and clinical chemistry parameters including liver enzymes (LEs) and total
      bilirubin (TBR). Severe hepatotoxicity was defined as a grade > or =3 elevation
      in at least one of the tested LEs or TBR levels while on therapy. Analysis of
      predictive factors was focused on increases in aspartate aminotransferase (ASAT)
      and/or alanine aminotransferase (ALAT) to grade > or =2. Grade > or =3 elevation
      developed with an incidence of 0.15 per patient year (PY); only 3.4% of the
      patients developed grade > or =3 values for ASAT and/or ALAT (incidence 0.03 per
      PY). We found that patients who use a protease inhibitor (PI) in a nevirapine
      containing regimen and patients who have chronic hepatitis B (HBV) infection are
      at a higher risk for the development of increases in ASAT and/or ALAT to grade >
      or =2. In contrast, the plasma concentration of nevirapine does not appear to be
      a predictive factor in this study population.

PMID- 12220976
TI  - Current advances in the phylogenetic reconstruction of metazoan evolution. A new
      paradigm for the Cambrian explosion?
AB  - The study of metazoan evolution has fascinated biologists for centuries, and it
      will certainly keep doing so. Recent interest on the origin of metazoan body
      plans, early metazoan evolution, genetic mechanisms generating disparity and
      diversity, molecular clock information, paleontology, and biogeochemistry is
      contributing to a better understanding of the current phyletic diversity.
      Unfortunately, the pattern of the metazoan tree of life still shows some
      important gaps in knowledge. It is the aim of this article to review some of the
      most important issues related to the inference of the metazoan tree, and point
      towards possible ways of solving certain obscure aspects in the history of animal
      evolution. A new hypothesis of the metazoan diversification during the Cambrian
      explosion is proposed by synthesizing ideas from phylogenetics, molecular
      evolution, paleontology, and developmental biology.

PMID- 12220977
TI  - The Radiata and the evolutionary origins of the bilaterian body plan.
AB  - The apparent conservation of cellular and molecular developmental mechanisms
      observed in a handful of bilaterian metazoans has spawned a "race" to reconstruct
      the bilaterian ancestor. Knowledge of this ancestor would permit us to
      reconstruct the evolutionary changes that have occurred along specific bilaterian
      lineages. However, comparisons among extant bilaterians provide an unnecessarily
      limited view of the ancestral bilaterian. Since the original bilaterians are
      believed by many to be derived from a radially symmetrical ancestor, additional
      evidence might be obtained by examining present-day radially symmetrical animals.
      We briefly review pertinent features of the body plans of the extant radial
      eumetazoan phyla, the Cnidaria, and Ctenophora, in the context of revealing
      potential evolutionary links to the bilaterians.

PMID- 12220978
TI  - Hox clusters and bilaterian phylogeny.
AB  - A large Hox cluster comprising at least seven genes has evolved by gene
      duplications in the ancestors of bilaterians. It probably emerged from a mini
      cluster of three or four genes that was present before the divergence of
      cnidarians and bilaterians. The comparison of Hox structural data in bilaterian
      phyla shows that the genes of the anterior part of the cluster have been more
      conserved than those of the posterior part. Some specific signature sequences,
      present in the form of signature residues within the homeodomain or conserved
      peptides outside the homeodomain, constitute phylogenetic evidence for the
      monophyly of protostomes and their division into ecdysozoans and
      lophotrochozoans. These conserved motifs may provide decisive arguments for the
      phylogenetic position of some enigmatic phyla.

PMID- 12220979
TI  - Is the evolution of Cnox-2 Hox/ParaHox genes "multicolored" and
      "polygenealogical?".
AB  - Understanding the evolution of metazoan bauplans is linked to understanding the
      evolution of Hox and ParaHox genes. At the base of metazoan radiation we see in
      both cases a quite confusing picture yet. Here Cnox-2 is one of the best studied
      diploblast Hox genes. Homologs of this gene are known from Placozoa and several
      Cnidaria. In those cases where full length gene sequences, or at least full
      length homeobox sequences, are available the relationship to Hox genes from
      triploblastic animals as well as the classification to Hox or ParaHox genes can
      be controversially discussed. The existing data on possible gene functions also
      reveal a quite heterogeneous picture. It seems conceivable that part of the
      "multicolored" picture relates to a "polygenealogical" origin of the Cnox-2 gene.

PMID- 12220980
TI  - Phylogeny, fossils, and model systems in the study of evolutionary developmental
      biology.
AB  - The emerging field of evolutionary developmental biology (evo-devo) continues to
      operate largely under a single paradigm. In this paradigm developmental
      regulatory genes and processes are compared among a collection of "model
      organisms" selected primarily on the basis of their historical utility in the
      study of development. This approach has proven to be extremely informative,
      revealing an unexpected deep evolutionary conservation among developmental genes
      and genetic systems. Despite its success, concern has been expressed regarding
      its limitations. We discuss the "model organism" paradigm in evo-devo research.
      Based on our interpretation of its limitations, we propose a separate but
      complementary approach that is centered on "model groups." These groups are
      selected on the basis of their taxonomic affinity and their relevance to
      questions of interest to evo-devo biologists. We further discuss the
      Tetraodontiformes (Teleostei, Pisces) as an example of a "model group" for the
      evo-devo study of vertebrate skeletal elements.

PMID- 12220981
TI  - Tribolium Hox genes repress antennal development in the gnathos and trunk.
AB  - Evidence from Drosophila suggests that Hox genes not only specify regional
      identity, but have the additional function of repressing antennal development
      within their normal domains. This is dramatically demonstrated by a series of Hox
      mutants in the red flour beetle, Tribolium castaneum, and is likely an ancient
      function of Hox genes in insects.

PMID- 12220982
TI  - An automated phylogenetic key for classifying homeoboxes.
AB  - When novel gene sequences are discovered, they are usually identified,
      classified, and annotated based on aggregate measures of sequence similarity.
      This method is prone to errors, however. Phylogenetic analysis is a more accurate
      basis for gene classification and ortholog identification, but it is relatively
      labor-intensive and computationally demanding. Here we report and demonstrate a
      rapid new method for gene classification based on phylogenetic principles. Given
      the phylogeny of a minimal sample of gene family members, our method
      automatically identifies amino acids that are phylogenetically characteristic of
      each class of sequences in the family; it then classifies a novel sequence based
      on the presence of these characteristic attributes in its sequence. Using a
      subset of homeobox protein sequences as a test case, we show that our method
      approximates classification based on full-scale phylogenetic analysis with very
      high accuracy in a tiny fraction of the time.

PMID- 12220983
TI  - Establishing character correspondence for sensory organ traits in flies: sensory
      organ development provides insight for reconstructing character evolution.
AB  - In Diptera and in other insects sensory organ patterns play an important role in
      the construction of phylogenies based on morphological characters. In this paper
      I explore the developmental basis for sensory organ pattern transformations
      between and within species. Knowledge of the properties of sensory organ
      development provides a foundation to judge the correspondence relationships
      between sensory organs. This is used to explore what components of notum bristle
      patterns are equivalent across the Schizophora. By investigating patterning
      processes in leg development, and their conservation across holometabolous
      insects, I show ways of relating specialised leg vestiture between species.
      Sensory organ patterns on the legs are diversified under homeotic gene control,
      potentially adding patterns of homeotic variation between legs to the list of
      informative traits for phylogenetic analysis. Correspondence relationships
      between wing and haltere sensory organ fields are resolved by exploring homeotic
      gene action in detail.

PMID- 12220984
TI  - Ciona intestinalis ParaHox genes: evolution of Hox/ParaHox cluster integrity,
      developmental mode, and temporal colinearity.
AB  - The Hox gene cluster, and its evolutionary sister the ParaHox gene cluster,
      pattern the anterior-posterior axis of animals. The spatial and temporal
      regulation of the genes seems to be intimately linked to the gene order within
      the clusters. In some animals the tight organisation of the clusters has
      disintegrated. We note that these animals develop in a derived fashion relative
      to the norm of their respective lineages. Here we present the genomic
      organisation of the ParaHox genes of Ciona intestinalis, and note that tight
      clustering has been lost in evolution. We present a hypothesis that the Hox and
      ParaHox clusters are constrained as ordered clusters by the mechanisms producing
      temporal colinearity; when temporal colinearity is no longer needed or used
      during development, the clusters can fall apart. This disintegration may be
      mediated by the invasion of transposable elements into the clusters, and
      subsequent genomic rearrangements.

PMID- 12220985
TI  - Mutational analysis of the Bordetella pertussis wlb LPS biosynthesis locus.
AB  - Bordetella pertussis wlb is required for band A lipopolysaccharide (LPS)
      expression. We report the mutational analysis of this locus that supports
      previous gene function assignments that were made on the basis of sequence
      similarities.

PMID- 12220986
TI  - The neuropathology observed in wild-type mice inoculated with human poliovirus
      mirrors human paralytic poliomyelitis.
AB  - Human paralytic poliomyelitis results from the destruction of spinal cord
      anterior horn motor neurons by human poliovirus (PV). CNS disease pathology
      similar to human poliomyelitis has been observed in experimentally infected
      chimpanzees, monkeys and wild-type mice. In this study we present a detailed
      examination of the clinical and histopathological features in the wild-type mouse
      after intracranial (i.c.) and novel intramuscular (i.m.) injection of poliovirus.
      Either route of poliovirus administration results in a clinical disease
      characterized predominately by flaccid paralysis. The observed histopathological
      features are compared with the histopathology reported for human paralytic
      poliomyelitis, experimentally infected chimpanzees, monkeys and transgenic mice
      expressing the human poliovirus receptor (hPVR). The observation of flaccid
      paralysis and anterior horn motor neuron destruction mirrors what is observed in
      human paralytic poliomyelitis. Our results suggest that the neuropathology
      observed in the wild-type mouse model is similar to what has been observed in
      both the human disease and in other experimental animal models, with the possible
      exception of the transgenic mouse model. The observed neuropathology of the wild
      type mouse model more closely reflects what has been observed in human
      poliomyelitis, as well as in experimentally infected chimpanzees and monkeys,
      than does the hPVR transgenic mouse model. The previously reported poliovirus
      induced white matter demyelinating disease was not observed.

PMID- 12220987
TI  - Pseudomonas aeruginosa outer membrane protein F is an adhesin in bacterial
      binding to lung epithelial cells in culture.
AB  - Adherence to host cells is a crucial step by which bacteria initiate an infection
      but the bacterial determinants of the process are, as yet, poorly understood. In
      an effort to identify bacterial adhesins responsible for Pseudomonas aeruginosa
      binding to host cells, we identified porin F (OprF) from the outer membrane of P.
      aeruginosa as adhesin for human alveolar epithelial (A549) cells. Bacterial
      adhesion assays with (35)S-labeled wild type P. aeruginosa and its isogenic
      mutant strain lacking OprF showed that the mutant strain binds 43% less than the
      wild type to A549 cells (P<0.01). In addition, bacterial binding is significantly
      reduced (P<0.01) when either A549 cells were pretreated with purified OprF or if
      bacteria were pre-incubated with a monoclonal antibody to OprF. Finally, ligand
      binding experiments in which purified OprF protein was added to A549 monolayers
      showed saturable binding. These data indicate that OprF contributes to bacterial
      adherence to A549 epithelial cells and could facilitate Pseudomonas interactions
      with the epithelium, including colonization of the airway epithelium or the
      initiation of pulmonary infection.

PMID- 12220988
TI  - Bordetella pertussis infection of human respiratory epithelial cells up-regulates
      intercellular adhesion molecule-1 expression: role of filamentous hemagglutinin
      and pertussis toxin.
AB  - Adhesion molecules on respiratory epithelial cells play a critical role in
      inflammatory cell recruitment and accumulation at sites of inflammation.
      Bordetella pertussis colonizes the human respiratory tract by infecting
      epithelial cells, leading to an inflammatory response. In this study, the role of
      bacterial factors in the expression of intercellular adhesion molecule-1 (ICAM-1)
      on human respiratory epithelial cells was investigated in response to B.
      pertussis. Flow cytometry and real time RT-PCR analysis showed that BEAS-2B human
      bronchial epithelial cells expressed increased levels of ICAM-1 mRNA and surface
      protein in response to B. pertussis infection. Filamentous hemagglutinin (FHA)
      played a role in this response because of the impaired capability of a FHA
      deficient isogenic strain. A mutant strain in which an Arg-Gly-Asp (RGD) site of
      FHA had been changed to Arg-Ala-Asp had diminished ability to up-regulate ICAM-1
      expression. RGD sequence-associated up-regulation of ICAM-1 expression was also
      observed in primary normal human bronchial epithelial cells. Pretreatment of
      cells with integrin antagonists such as RGD-containing peptide and antibody
      against very late antigen-5 (VLA-5) inhibited the up-regulation of ICAM-1
      expression, suggesting the participation of VLA-5 integrin in this response.
      Pertussis toxin (PT) prevented the up-regulation of ICAM-1 expression because a
      PT-deficient mutant strain induced higher levels of ICAM-1 mRNA and surface
      protein than the parental strain. Consistent with this, purified PT suppressed
      the up-regulation of epithelial ICAM-1 expression. These findings demonstrate
      that B. pertussis FHA up-regulates ICAM-1 expression on respiratory epithelial
      cells through interaction of its RGD site with host cell VLA-5 integrin, and that
      PT impairs this response.

PMID- 12220989
TI  - An exocellular thermolysin-like metalloprotease produced by Vibrio fluvialis:
      purification, characterization, and gene cloning.
AB  - An exocellular metalloprotease produced by Vibrio fluvialis, an enteropathogenic
      vibrio, was purified and characterized. The metalloprotease (V. fluvialis
      protease [VFP]) was found to have very similar characteristics to V. vulnificus
      protease, including a molecular mass of 45kDa, sensitivity to chelating agents or
      competitive inhibitors for thermolysin-like metalloproteases, and the substrate
      specificity. The structural gene for VFP was also cloned, and its nucleotide
      sequence was determined. The deduced amino acid sequence confirmed that VFP was a
      member of the thermolysin family. VFP, like V. vulnificus protease, showed the
      haemagglutinating, permeability-enhancing and haemorrhagic activities in addition
      to the proteolytic activity toward oligopeptide, casein or elastin.

PMID- 12220990
TI  - Mutation of csk, encoding the C-terminal Src kinase, reduces Pseudomonas
      aeruginosa internalization by mammalian cells and enhances bacterial
      cytotoxicity.
AB  - Clinical isolates of Pseudomonas aeruginosa are either invasive or cytotoxic
      towards mammalian epithelial cells, endothelial cells, and macrophages. Invasion
      requires host cell actin cytoskeleton function, and ExsA-regulated proteins of P.
      aeruginosa that inhibit invasion (ExoS and ExoT) can disrupt the cytoskeleton.
      Another ExsA regulated protein, ExoU, is involved in the cytotoxic activity of
      cytotoxic strains. Src-family kinases are thought to participate in the
      regulation of cytoskeleton function. Recent studies have suggested that Src
      family tyrosine kinases, p60-Src and p59-Fyn, are activated during P. aeruginosa
      invasion. Using fibroblasts homozygous for mutation of csk (-/-), we tested the
      hypothesis that mutation of csk, encoding a negative regulator of Src-family
      tyrosine kinases, would be important in P. aeruginosa invasion and cytotoxicity.
      Mutation of csk was found to reduce invasion by approximately 8-fold, without
      reducing bacterial adherence to cells (P=0.0001). Conversely, csk (-/-) cells
      were approximately 5-fold more susceptible to ExoU-dependent cytotoxicity
      (P=0.024), which was accompanied by a small increase in ExsA-regulated adherence.
      ExoT-dependent invasion inhibitory activity of cytotoxic P. aeruginosa was
      attenuated in csk (-/-) cells as compared to normal fibroblasts. These data show
      that fibroblasts, like epithelial cells, are susceptible to P. aeruginosa
      invasion and cytotoxicity. They also show a role for Csk in P. aeruginosa
      invasion, while providing further evidence that actin cytoskeleton disruption
      contributes to ExsA-regulated P. aeruginosa cytotoxicity and invasion inhibition.

PMID- 12220991
TI  - Problems, obstacles and complications with transpalatal distraction in non
      congenital deformities.
AB  - INTRODUCTION: The transpalatal distractor is a bone-borne device that eliminates
      negative orthodontic effects during and after maxillary expansion. It produces
      virtually parallel expansion in the coronal plane. Orthodontic appliances can be
      installed at an earlier date than when tooth-borne expanders are used. Our aim
      was to improve the technique by reviewing the difficulties encountered during
      applications in the past. PATIENTS AND METHODS: The files of 57 patients were
      analyzed for problems (difficulties requiring surgical intervention), obstacles
      (difficulties requiring surgical intervention but not interfering with the
      result), and complications (difficulties not resolved at the end of the
      treatment). RESULTS: Twenty-nine difficulties occurred. In 25 cases they were
      considered to be a 'problem'. Nine problems were surgery related and 16 problems
      were related to the distraction device itself (14 episodes of loosening of the
      module, two instances of loss of one osteosynthesis screw). 'Obstacles' occurred
      in three cases, i.e. loosening of an abutment plate. There was only one
      'complication': unilateral infraorbital hyposensibility in a case of a high level
      corticotomy. CONCLUSION: The expansion goal was achieved in all patients.
      Loosening of the module proved to be the major cause of discomfort. The incidence
      of difficulties has lead to a change in the design of the hardware and in the
      surgical protocol.

PMID- 12220992
TI  - Pinhole osteotomy in distraction osteogenesis - a technical note.
AB  - A new surgical approach for performing the mandibular osteotomy for distraction
      osteogenesis is described. In order to minimize trauma to bone caused by the
      osteotomy - and adjacent soft tissue - caused by excessive stretching - an
      additional transbuccal pinhole incision is made. The shaft of the saw blade is
      passed through this incision. This allows a precise cut of the mandibular ramus
      at the planned angle and easy guidance of the saw during the procedure. The
      method can be used both with extraoral or intraoral distraction devices in
      children and adults.

PMID- 12220993
TI  - Analysis of midface asymmetry in patients with cleft lip, alveolus and palate at
      the age of 3 months using 3D-COSMOS measuring system.
AB  - INTRODUCTION: Patients suffering from unilateral cleft lip, alveolus and palate
      exhibit a varying degree of asymmetry of the midface. Evaluation of this
      asymmetry can be carried out by means of 3D-CT, or a laser surface scanner.
      MATERIAL AND METHODS: In this paper, 3D-CT-scan data of 21 patients with
      unilateral clefts of lip, alveolus and palate were analysed using three
      dimensional models. Evaluations of the 3D-models were carried out with the
      computer-aided 3D-operation simulator 3D-Cosmos. RESULTS: Asymmetry was found in
      the orbital, nasal and maxillary regions. The infraorbital rims were displaced
      craniocaudally and horizontally as well as laterally of the cleft-sided piriform
      aperture. This asymmetry corresponded to a dislocation of the maxillary segment
      on the cleft side. A deficit in volume was not reliably found.

PMID- 12220994
TI  - 2D- and 3D-based measurements of orbital floor fractures from CT scans.
AB  - OBJECTIVE: Two methods for area and volume calculation of the orbit were
      evaluated following blow-out fractures of the orbital floor using computed
      tomography (CT) scans. MATERIAL AND METHODS: Isolated blow-out fractures of the
      orbital floor in human cadavers were simulated by fracturing the orbital floor
      and placing a defined volume of silicone within each defect. The area of fracture
      and the volume of silicone simulating herniated periorbital tissue were evaluated
      in 16 orbits by the use of a three-dimensional (3D) CT-based software package
      (Analyze((R)); Mayo Clinic, Rochester, MN, USA) and software based on two
      dimensional (2D) coronal CT scans. Both methods were compared with direct
      anatomical measurements and evaluated with Lin's concordance coefficient
      (rho(c)). RESULTS: Between-method concordance of area and volume calculation were
      rho(c)=0.962, and 0.872 for the 3D-CT-based method, and 0.981 and 0.952 for the
      2D-CT method, respectively. The time allocated for measurement was significantly
      longer for the 3D-CT than for the 2D-CT method (p<0.001). CONCLUSION:
      Calculations of blow-out fractures of the orbital floor by 3D-CT and 2D-CT method
      are accurate for assessing the area of fracture and the volume of herniated
      tissue. Lesser processing time and simple usage favour the 2D-CT-based
      calculation method.

PMID- 12220995
TI  - Photoelastic analysis of bone deformation in the region of the mandibular condyle
      during mastication.
AB  - INTRODUCTION: The purpose of this experimental study was to demonstrate the
      stress patterns arising in the region of the mandibular condyle during
      mastication. MATERIAL AND METHOD: Stress analysis was performed using reflection
      photoelasticity to demonstrate deformation occurring on the surface of the
      mandible. The rami of three fresh dentate human mandibles were coated with a
      shell of photoelastic resin. Using a novel loading device, these mandibles were
      then subjected to external forces (muscular traction, resultant mandibular forces
      and intra-articular reaction force) reproducing a unilateral biting task between
      the first right molars. Deformations were measured from the working side.
      RESULTS: The trace of isostatic lines from the isoclinic fringes revealed major
      differences in stress distributions between the three mandibles. These
      differences were attributed to differences in shape between the three mandibles.
      Conversely, we consistently found compressive stress patterns along the posterior
      border of the ramus and tensile stress patterns along the anterior border of the
      ramus and in the zone situated below the siqmoid notch. CONCLUSION: These
      findings suggest that during this particular task, the mandible is subjected to
      sagittal forces which tend to straighten the mandibular angle. This implies that
      new concepts are needed for the positioning of osteosynthesis plates in the
      condylar region, close to the tensile strain lines, as has been recommended also
      for other parts of the mandible when applying semi-rigid internal fixation.

PMID- 12220996
TI  - Finite element analysis of the stresses around endosseous implants in various
      reconstructed mandibular models.
AB  - PURPOSE: To calculate the location and intensity of the maximum stresses
      occurring around implants in the reconstructed mandible. MATERIAL AND METHODS:
      Human preserved mandibles and fibulae were used to design 3-D mandibular models
      on a Desktop Computer. Various 3-D simulation models representing mandibles were
      made. Implants (fixtures) and superstructures were then embedded in each model
      and occlusal pressure was applied to the cantilever portion of the
      superstructure. Von Mises stress, the maximum and minimum principal stress on
      each model were calculated using finite element structural analysis software.
      Finally, evaluation of the stresses around each fixture hole was performed.
      RESULTS: It appeared that for each fixture hole, the direction and the magnitude
      of the stresses were influenced by complex factors such as the thickness of the
      cortical bone where the fixtures were embedded, the degree of vertical
      displacement under load, and the relationship between adjacent fixtures.
      CONCLUSION: Location and intensity of the stresses occurring around fixtures
      differs significantly between various types of mandibular reconstruction.
      Published by Elsevier Science Ltd.

PMID- 12220997
TI  - Changes of the collagen fibre arrangement of the rabbit temporomandibular joint
      following discectomy.
AB  - PURPOSE: The purpose of the present study is to examine changes in arrangement of
      collagen fibres of the temporomandibular joint (TMJ) following discectomy.
      MATERIAL AND METHODS: Twelve male Japanese white rabbits were used. The right
      TMJs of six rabbits were surgically exposed, and the disc removed with a scalpel.
      Three untreated and three sham-operated rabbits were used as controls. The TMJs
      were removed in three rabbits 1 month and in three other rabbits, 3 months after
      discectomy and processed for demonstration of collagen fibres. RESULTS: One month
      after discectomy, collagen fibres in the fibrous layers of condyle and articular
      eminence were of various sizes and were running in various directions. Collagen
      fibres in the cartilaginous layers were sparser in the study TMJs than in the
      control TMJs. Three months after discectomy, the direction of collagen fibres in
      the fibrous layers of the condyle and articular eminence became organized and
      were similar to that in the control TMJs. However, collagen fibres in the
      cartilaginous layers of the condyle remained sparser 3 months after discectomy
      than in the control TMJs. CONCLUSION: Experimental discectomy in the rabbit
      alters the distribution and density of collagen fibres in the TMJ. Thorough
      postoperative follow-up seems to be necessary after discectomy.

PMID- 12220998
TI  - An anatomical study of vascularized iliac bone grafts for dental implantation.
AB  - PURPOSE: The purpose of this study was to clarify the anatomical features of
      vascularized iliac bone grafts used for mandibular reconstruction and dental
      implantation. MATERIAL AND METHOD: Twenty-six cadavers were dissected to examine
      vessels and areas of iliac bone that could be used as pedicles and grafts. The
      length and diameter of vessels of the vascular pedicle were determined, and the
      length and depths of the iliac bone were measured with respect to points
      determined by the relative dimensions of the bone. RESULTS: The deep circumflex
      iliac arteries were classified as double nutrient type (75%), iliac-crest type
      (19%), or iliacus-muscle type (6%). The mean arterial length was 64+/-15 mm in
      the double nutrient type. The mean internal diameters at the origin of the deep
      circumflex iliac artery and vein that could be used for anastomosis were 1.7+/
      0.4 mm and 2.1+/-0.7 mm respectively. The greatest mean cross-sectional width and
      height were 18+/-3 and 42+/-5 mm respectively. The greatest mean cross-sectional
      cortical thickness at the intermediate line of the iliac crest was 3.4+/-0.8 mm.
      CONCLUSION: These results should be useful in designing bone grafts for
      mandibular reconstruction followed by dental implantation.

PMID- 12220999
TI  - An unusual anomaly of the radial artery with potential significance to the
      forearm free flap. Case report.
AB  - INTRODUCTION: The radial forearm free flap has become the favourite transplant
      for microsurgical repair of small-to-medium sized soft tissue defects of the oral
      cavity. This flap derives its blood supply from perforators of the radial artery.
      As the radial forearm flap gains ever more popularity, it is likely that
      anomalous forearm vascular patterns will be encountered by more surgeons.
      PURPOSE: In this paper, a rare anomaly found in a patient during flap elevation
      is described. This 63-year-old male had a squamous cell carcinoma of the floor of
      the mouth and a radial forearm free flap was harvested to repair the defect.
      During this procedure an aberrant duplication of the radial artery was found
      which could have significance in harvesting such a flap in other patients.
      CONCLUSION: There are anomalies of the radial artery that may jeopardize the
      vascular supply to the radial forearm free flap. Surgeons performing this flap
      must be aware of the most common variants of the vascular anatomy of the forearm.

PMID- 12221001
TI  - Molecular regulation of vertebrate early endoderm development.
AB  - Detailed study of the ectoderm and mesoderm has led to increasingly refined
      understanding of molecular mechanisms that operate early in development to
      generate cellular diversity. More recently, a number of powerful studies have
      begun to characterize the molecular determinants of the endoderm, a germ layer
      previously neglected in developmental biology. Work in diverse model systems has
      converged on an integrated transcriptional and signaling pathway that serves to
      establish the vertebrate endoderm. A T-box transcription factor identified in
      Xenopus embryos, VegT, appears to function near the top of an endoderm-specifying
      transcriptional hierarchy. VegT activates and reinforces Nodal-related TGFbeta
      signaling and also induces expression of essential downstream transcriptional
      regulators, Mix-like paired-homeodomain and GATA factors. These proteins
      cooperate to regulate expression of a relay of HMG-box Sox-family transcription
      factors culminating with Sox 17, which may be an obligate mediator of vertebrate
      endoderm development. This review synthesizes findings in three vertebrate model
      organisms and discusses these genetic interactions in the context of the
      progressive acquisition of endodermal identity early in vertebrate development.

PMID- 12221002
TI  - Developmental expression and biochemical characterization of Emu family members.
AB  - Kidney development has often served as a model for epithelial-mesenchymal cell
      interaction where the branching epithelium of the ureteric bud induces the
      metanephrogenic mesenchyme to form epithelial nephrons. In a screen for genes
      differentially expressed during kidney development, we have identified a novel
      gene that is dynamically expressed in the branching ureter and the developing
      nephrons. It was designated Emu1 since it shares an N-terminal cysteine-rich
      domain with Emilin1/2 and Multimerin. This highly conserved EMI domain is also
      found in another novel protein (Emu2) of similar protein structure: an N-terminal
      signal peptide followed by the EMI domain, an interrupted collagen stretch, and a
      conserved C-terminal domain of unknown function. We identified two further
      secreted EMI domain proteins, prompting us to compare their gene and protein
      structures, the EMI domain phylogeny, as well as the embryonic expression pattern
      of known (Emilin1/2, Multimerin) and novel (Emu1/2, Emilin3, Multimerin2) Emu
      gene family members. Emu1 and Emu2 not only show a similar structural
      organization, but furthermore a striking complementary expression in organs
      developing through epithelial-mesenchymal interactions. In these tissues, Emu1 is
      restricted to epithelial and Emu2 to mesenchymal cells. Preliminary biochemical
      analysis of Emu1/2 confirmed that they are secreted glycoproteins which are
      attached to the extracellular matrix and capable of forming homo- and heteromers
      via disulfide bonding. The widespread, but individually distinct expression
      patterns of all Emu gene family members suggest multiple functions during mouse
      embryogenesis. Their multidomain protein structure may indicate that Emu proteins
      interact with several different extracellular matrix components and serve to
      connect and integrate the function of multiple partner molecules.

PMID- 12221003
TI  - Pax3-expressing trigeminal placode cells can localize to trunk neural crest sites
      but are committed to a cutaneous sensory neuron fate.
AB  - The cutaneous sensory neurons of the ophthalmic lobe of the trigeminal ganglion
      are derived from two embryonic cell populations, the neural crest and the paired
      ophthalmic trigeminal (opV) placodes. Pax3 is the earliest known marker of opV
      placode ectoderm in the chick. Pax3 is also expressed transiently by neural crest
      cells as they emigrate from the neural tube, and it is reexpressed in neural
      crest cells as they condense to form dorsal root ganglia and certain cranial
      ganglia, including the trigeminal ganglion. Here, we examined whether Pax3+ opV
      placode-derived cells behave like Pax3+ neural crest cells when they are grafted
      into the trunk. Pax3+ quail opV ectoderm cells associate with host neural crest
      migratory streams and form Pax3+ neurons that populate the dorsal root and
      sympathetic ganglia and several ectopic sites, including the ventral root. Pax3
      expression is subsequently downregulated, and at E8, all opV ectoderm-derived
      neurons in all locations are large in diameter, and virtually all express TrkB.
      At least some of these neurons project to the lateral region of the dorsal horn,
      and peripheral quail neurites are seen in the dermis, suggesting that they are
      cutaneous sensory neurons. Hence, although they are able to incorporate into
      neural crest-derived ganglia in the trunk, Pax3+ opV ectoderm cells are committed
      to forming cutaneous sensory neurons, their normal fate in the trigeminal
      ganglion. In contrast, Pax3 is not expressed in neural crest-derived neurons in
      the dorsal root and trigeminal ganglia at any stage, suggesting either that Pax3
      is expressed in glial cells or that it is completely downregulated before
      neuronal differentiation. Since Pax3 is maintained in opV placode-derived neurons
      for some considerable time after neuronal differentiation, these data suggest
      that Pax3 may play different roles in opV placode cells and neural crest cells.

PMID- 12221004
TI  - Extensive cell movements accompany formation of the otic placode.
AB  - During development, the vertebrate inner ear arises from the otic placode, a
      thickened portion of the ectoderm next to the hindbrain. Here, the first detailed
      fate maps of this region in the chick embryo are presented. At head process
      stages, placode precursors are scattered throughout a large region of the
      embryonic ectoderm, where they intermingle with future neural, neural crest,
      epidermal, and other placode cells. Within the next few hours, dramatic cell
      movements shift the future otic placode cells toward the midline and ultimately
      result in convergence to their final position next to rhombomeres 5-6. Individual
      cells and small cell groups undergo constant cell rearrangements and appear to
      sort out from nonotic cells. While the major portion of the otic placode is
      derived from the nonneural ectoderm, the neural folds also contribute cells to
      the placode at least until the four-somite stage. Comparison of these fate maps
      with gene expression patterns at equivalent stages reveals molecular
      heterogeneity of otic precursor cells in terms of their expression of dlx5, msx1,
      Six4, and ERNI. Although Pax2 expression coincides with the region where otic
      precursors are found from stage 8, not all Pax2-positive cells will ultimately
      contribute to the otic placode.

PMID- 12221005
TI  - Target-independent specification of proprioceptive sensory neurons.
AB  - Previous studies in the chick embryo have shown that sensory neurons fail to
      innervate muscle in the absence of motor neurons. Instead, motor neuron deletion
      causes more sensory axons to project to the skin. We used this experimental
      paradigm to determine when sensory neurons are specified to become proprioceptive
      afferents. Experimental embryos were treated with either saline or exogenous
      neurotrophin-3 (NT-3) to promote the survival of proprioceptive afferents. In
      saline-treated embryos, motor neuron deletion caused an increase in sensory
      neuron apoptosis on the deleted side, an effect reversed by NT3. Motor neuron
      deletion also eliminated the sartorious muscle nerve, as previously reported. In
      NT3-treated embryos, this altered nerve pattern was accompanied by the
      enlargement of the adjacent cutaneous nerve. These embryos were further analyzed
      by using immunohistochemistry for trkC (a receptor for NT3) retrograde and
      transganglionic labeling. Our results show that, following motor neuron deletion,
      more trkC+ afferents project in cutaneous nerves on the deleted side of NT3
      treated embryos. Transganglionic labeling demonstrated that at least some of
      these neurons made spinal projections that are typical of proprioceptive
      afferents. These results therefore indicate that the proprioceptive phenotype is
      specified prior to target innervation and that these neurons can retain their
      identity despite projecting to inappropriate (cutaneous) targets.

PMID- 12221006
TI  - Ectodermal FGFs induce perinodular inhibition of limb chondrogenesis in vitro and
      in vivo via FGF receptor 2.
AB  - The formation of cartilage elements in the developing vertebrate limb, where they
      serve as primordia for the appendicular skeleton, is preceded by the appearance
      of discrete cellular condensations. Control of the size and spacing of these
      condensations is a key aspect of skeletal pattern formation. Limb bud cell
      cultures grown in the absence of ectoderm formed continuous sheet-like masses of
      cartilage. With the inclusion of ectoderm, these cultures produced one or more
      cartilage nodules surrounded by zones of noncartilaginous mesenchyme. Ectodermal
      fibroblast growth factors (FGF2 and FGF8), but not a mesodermal FGF (FGF7),
      substituted for ectoderm in inhibiting chondrogenic gene expression, with some
      combinations of the two ectodermal factors leading to well-spaced cartilage
      nodules of relatively uniform size. Treatment of cultures with SU5402, an
      inhibitor FGF receptor tyrosine kinase activity, rendered FGFs ineffective in
      inducing perinodular inhibition. Inhibition of production of FGF receptor 2
      (FGFR2) by transfection of wing and leg cell cultures with antisense
      oligodeoxynucleotides blocked appearance of ectoderm- or FGF-induced zones of
      perinodular inhibition of chondrogenesis and, when introduced into the limb buds
      of developing embryos, led to shorter, thicker, and fused cartilage elements.
      Because FGFR2 is expressed mainly at sites of precartilage condensation during
      limb development in vivo and in vitro, these results suggest that activation of
      FGFR2 by FGFs during development elicits a lateral inhibitor of chondrogenesis
      that limits the expansion of developing skeletal elements.

PMID- 12221007
TI  - Novel behavioral and developmental defects associated with Drosophila single
      minded.
AB  - In Drosophila, the development of the midline cells of the embryonic ventral
      nerve cord depends on the function of the bHLH-PAS transcription factor Single
      minded (Sim). The expression domain of sim, however, is also found anterior and
      posterior to the developing ventral cord throughout the germ band. Indeed,
      mutations in sim were identified based on their characteristic cuticle phenotype.
      Eight abdominal segments (A1-A8) can be easily seen in the larval cuticle, while
      three more can be identified during embryogenesis. Cells located in A8-A10 give
      rise to the formation of the genital imaginal discs, and a highly modified A11
      segment gives rise to the anal pads that flank the anus. sim is expressed in all
      these segments and is required for the formation of both the anal pads and the
      genital imaginal discs. A new temperature-sensitive sim allele allowed an
      assessment of possible postembryonic function(s) of sim. Reduction of sim
      function below a 50% threshold leads to sterile flies with marked behavioral
      deficits. Most mutant sim flies were only able to walk in circles. Further
      analyses indicated that this phenotype is likely due to defects in the brain
      central complex. This brain region, which has previously been implicated in the
      control of walking behavior, expresses high levels of nuclear Sim protein in
      three clusters of neurons in each central brain hemisphere. Additional Sim
      localization in the medullary and laminar neurons of the optic lobes may
      correlate with the presence of ectopic axon bundles observed in the optic lobes
      of sim mutant flies.

PMID- 12221008
TI  - The pattern of neurovascular development in the forelimb of the quail embryo.
AB  - Peripheral nerve and vascular patterns are congruent in the adult vertebrate, but
      this has been disputed in vertebrate embryos. The most detailed of these studies
      have used the avian forelimb as a model system, yet neurovascular anatomical
      relationships and critical vascular remodeling events remain inadequately
      characterized in this model. To address this, we have used a combination of
      intravascular marker injection, multilabel fluorescent stereomicroscopy, and
      confocal microscopy to analyze the spatiotemporal relationships between
      peripheral nerves and blood vessels in the forelimb of 818 quail embryos from E2
      (HH13) to E15 (HH41). We find that the neurovascular anatomical relationships
      established during development are highly stereotypic and congruent. Blood
      vessels typically arise before their corresponding nerves, but there are several
      critical exceptions to this rule. The vascular pattern is extensively remodeled
      from the earliest stage examined (E2; HH13), whereas the peripheral nerves, the
      first of which enter the forelimb at E3.5-E4 (HH21-HH24), have a progressively
      unfolding pattern that, once formed, remains essentially unchanged. The adult
      neurovascular pattern is not established until E8 (HH34). Peripheral nerves are
      always found to track close and parallel to the vasculature. As they track
      distally, peripheral nerves always lie on the side of the vasculature away from
      the center of the forelimb. Neurovascular patterns have a hierarchy of congruence
      that is highest in the dorsoventral plane, followed by the anteroposterior, and
      lastly the proximodistal planes.

PMID- 12221009
TI  - Crossing the ventral midline causes neurons to change their response to floor
      plate and alar plate attractive cues during transmedian migration.
AB  - Neuronal migration is required for the establishment of specific neural
      structures, such as layers and nuclei. Neurons migrate along specific migratory
      routes toward their final destinations, sometimes across long distances. However,
      the cellular and molecular interactions that control neuronal migration are
      largely unknown. Here, we examined the mechanism underlying the transmedian
      migration of precerebellar neurons using a flat whole-mount preparation of the
      rat embryo. These neurons were initially attracted by the floor plate (FP) at the
      ventral midline. However, after crossing the midline, they lost their
      responsiveness to the FP and became attracted by the alar plate (AP). Although
      the loss of responsiveness to FP cues was caused by an encounter of migrating
      cells with the FP, the gain of responsiveness to AP cues occurred irrespective of
      their encounter with the FP. These results identify a crucial change in the
      response of migrating cells to attractive guidance cues during the transmedian
      migration of precerebellar neurons.

PMID- 12221010
TI  - Cyclical generation and degeneration of organs in a colonial urochordate involves
      crosstalk between old and new: a model for development and regeneration.
AB  - Botryllus schlosseri is a colonial marine urochordate in which all adult
      organisms (called zooids) in a colony die synchronously by apoptosis (programmed
      cell death) in cyclical fashion. During this death phase called takeover, cell
      corpses within the dying organism are engulfed by circulating phagocytic cells.
      The "old" zooids and their organs are resorbed within 24-36 h (programmed cell
      removal). This process coincides temporally with the growth of asexually derived
      primary buds, that harbor a small number of undifferentiated cells, into mature
      zooids containing functional organs and tissues with the same body plan as adult
      zooids from which they budded. Within these colonies, all zooids share a
      ramifying network of extracorporeal blood vessels embedded in a gelatinous tunic.
      The underlying mechanisms regulating programmed cell death and programmed cell
      removal in this organism are unknown. In this study, we extirpated buds or zooids
      from B. schlosseri colonies in order to investigate the interplay that exists
      between buds, zooids, and the vascular system during takeover. Our findings
      indicate that, in the complete absence of buds (budectomy), organs from adult
      zooids underwent programmed cell death but were markedly impaired in their
      ability to be resorbed despite engulfment of zooid-derived cell corpses by
      phagocytes. However, when buds were removed from only half of the flower-shaped
      systems of zooids in a colony (hemibudectomy), the budectomized zooids were
      completely resorbed within 36-48 h following onset of programmed cell death.
      Furthermore, if hemibudectomies were carried out by using small colonies, leaving
      only a single functional bud, zooids from the old generation were also resorbed,
      albeit delayed to 48-60 h following onset of programmed cell death. This bud
      eventually reached functional maturity, but grew significantly larger in size
      than any control zooid, and exhibited hyperplasia. This finding strongly
      suggested that components of the dying zooid viscera could be reutilized by the
      developing buds, possibly as part of a colony-wide recycling mechanism. In order
      to test this hypothesis, zooids were surgically removed (zooidectomy) at the
      onset of takeover, and bud growth was quantitatively determined. In these
      zooidectomized colonies, bud growth was severely curtailed. In most solitary,
      long-lived animals, organs and tissues are maintained by processes of continual
      death and removal of aging cells counterbalanced by regeneration with stem and
      progenitor cells. In the colonial tunicate B. schlosseri, the same kinds of
      processes ensure the longevity of the colony (an animal) by cycles of death and
      regeneration of its constituent zooids (also animals).

PMID- 12221011
TI  - Sonic hedgehog activates mesenchymal Gli1 expression during prostate ductal bud
      formation.
AB  - Ductal budding in the developing prostate is a testosterone-dependent event that
      involves signaling between the urogenital sinus epithelium (UGE) and urogenital
      sinus mesenchyme (UGM). We show here that ductal bud formation is associated with
      focused expression of Sonic hedgehog (Shh) in the epithelium of nascent prostate
      buds and in the growing tips of elongating prostate ducts. This pattern of
      localized Shh expression occurs in response to testosterone stimulation. The gene
      for the Shh receptor, Ptc1, is expressed in the UGM, as are the members of the
      Gli gene family of transcriptional regulators (Gli1, Gli2, and Gli3). Expression
      of Ptc1, Gli1, and Gli2 is localized primarily to mesenchyme surrounding prostate
      buds, whereas Gli3 is expressed diffusely throughout the UGM. A strong dependence
      of Gli1 (and Ptc1) expression on Shh signaling is demonstrated by induction of
      expression in both the intact urogenital sinus and the isolated UGM by exogenous
      SHH peptide. A similar dependence of Gli2 and Gli3 expression on Shh is not
      observed. Nonetheless, the chemical inhibitor of Shh signaling, cyclopamine,
      produced a graded inhibition of Gli gene expression (Gli1>Gli2>Gli3) in
      urogenital sinus explants that was paralleled by a severe inhibition of ductal
      budding.

PMID- 12221012
TI  - Constitutively active myosin light chain kinase alters axon guidance decisions in
      Drosophila embryos.
AB  - Conventional myosin II activity provides the motile force for axon outgrowth, but
      to achieve directional movement during axon pathway formation, myosin activity
      should be regulated by the attractive and repulsive guidance cues that guide an
      axon to its target. Here, evidence for this regulation is obtained by using a
      constitutively active Myosin Light Chain Kinase (ctMLCK) to selectively elevate
      myosin II activity in Drosophila CNS neurons. Expression of ctMLCK pan-neurally
      or in primarily pCC/MP2 neurons causes these axons to cross the midline
      incorrectly. This occurs without altering cell fates and is sensitive to
      mutations in the regulatory light chains. These results confirm the importance of
      regulating myosin II activity during axon pathway formation. Mutations in the
      midline repulsive ligand Slit, or its receptor Roundabout, enhance the number of
      ctMLCK-induced crossovers, but ctMLCK expression also partially rescues
      commissure formation in commissureless mutants, where repulsive signals remain
      high. Overexpression of Frazzled, the receptor for midline attractive Netrins,
      enhances ctMLCK-dependent crossovers, but crossovers are suppressed when Frazzled
      activity is reduced by using loss-of-function mutations. These results confirm
      that proper pathway formation requires careful regulation of MLCK and/or myosin
      II activity and suggest that regulation occurs in direct response to attractive
      and repulsive cues.

PMID- 12221013
TI  - Changes in phosphodiesterase activity in the developing rat submandibular gland.
AB  - Developmental changes (from 2 to 26 weeks) in phosphodiesterase (PDE) activity in
      the rat submandibular gland were investigated. Major activities for both cAMP-
      and cGMP-PDE were present in the 100000 x g supernatant fractions (70-90% of
      total activities), but not in the pellet fractions, during development. The
      effects of stimulators (Ca(2+)/calmodulin and cGMP) and inhibitors (cGMP,
      cilostamide, rolipram and zaprinast) were investigated in the supernatant
      fractions. During development, PDE4 (cAMP-specific PDE) was a major PDE,
      indicating that the majority of cAMP is hydrolysed by PDE4. In the young rat,
      PDE1 hydrolysed cGMP three-fold more than the control, and PDE2 (cGMP-stimulated
      PDE) was present, indicating that the concentration of intracellular cGMP may be
      enhanced, and cGMP may function in the growth pathway in the submandibular gland.
      Chromatograms eluted on a Mono Q HR5/5 ion-exchange column supported the results
      of the inhibition studies: PDE1, PDE2, PDE3, PDE4 and PDE5 were present in the
      young submandibular gland, and PDE1, PDE3, PDE4 and PDE5 in the adult gland.
      Expression of PDE5 was detected by inhibition studies, reverse transcriptase
      polymerase chain reaction and Western blotting in the submandibular gland.

PMID- 12221014
TI  - The effect of fibroblast growth factor-2 on the osteoinductive activity of
      recombinant human bone morphogenetic protein-2 in rat muscle.
AB  - To clarify the effect of recombinant human basic fibroblast growth factor (FGF-2)
      on the osteoinductive activity of recombinant human bone morphogenetic protein-2
      (BMP-2) in vivo, different amounts of FGF-2 (0, 16, 80 and 400 ng, and 2, 10 and
      50 micro g: n=10 in each group), BMP-2 (2 micro g) and type I collagen as a
      carrier were mixed and implanted into rat calf muscles. Three weeks after
      implantation, compared with the controls, the radiopaque shadows of the implants
      were increased in the 16, 80 and 400 ng FGF-2-treated groups, but decreased in
      the 2, 10 and 50 micro g FGF-2-treated groups. In addition, alkaline phosphatase
      activity was increased in the 16, 80 and 400 ng FGF-2-treated groups but
      decreased in the 50 micro g FGF-2-treated group. Histological examination
      revealed increased bone formation in the 16, 80 and 400 ng FGF-2-treated groups.
      These results show that combined treatment with FGF-2 and BMP-2 has a biphasic
      effect on osteoinductive activity, i.e. it increases with low doses of FGF-2 and
      decreases with high doses of FGF-2.

PMID- 12221015
TI  - Loss of heterozygosity on chromosome 7q in in vitro-immortalized human oral
      keratinocyte cell lines.
AB  - Loss of heterozygosity in two in vitro-immortalized human oral keratinocyte cell
      lines was analysed by polymerase chain reaction using 42 polymorphic
      microsatellite markers on chromosomes 4, 6, 7 and 15. These chromosomes are
      regarded as candidates for harbouring genes involved in the immortalization of
      human cells or tumour-suppressor genes in several tumours, including oral
      cancers, and karyotypic analysis has revealed that both cell lines have non
      random alterations in these chromosomes. No allele losses were detected at any
      informative loci on chromosomes 4 and 6 in the cell lines, including genomic
      regions adjacent to putative human tumour-suppressor genes and putative
      senescence genes. When analysed for loss of heterozygosity on chromosomes 7 and
      15, allele losses common to both cell lines were detected in the regions at
      7q11.2, 7q21.1-21.3 and 7q31.1. High frequencies of loss of heterozygosity on
      chromosome 7q in at least two distinct regions, particularly centred around 7q31,
      are observed in a variety of tumours, including oral squamous-cell carcinoma,
      suggesting that multiple genes involved in immortalization of these cell lines
      might be present on chromosome 7q.

PMID- 12221016
TI  - Structural characterisation of cysteines in a bacterial-binding motif of human
      salivary mucin MG2.
AB  - Human salivary mucin MG2 is a 180 kDa glycoprotein secreted by
      submandibular/sublingual and minor salivary glands. Secreted MG2 contains a
      domain with the only two cysteines (Cys(45) and Cys(50)) present in the
      polypeptide backbone; in native and recombinant MG2 this domain is involved in
      mucin binding to oral microbes. As the reduction and alkylation of MG2 has been
      shown to abolish binding, the present study was undertaken to determine whether
      the cysteine residues exist in the dithiol or disulphide form. Electrophoretic
      analysis under reducing and non-reducing conditions showed that intermolecular
      disulphide bonds do not occur between MG2 molecules. The same incorporation of
      radiolabelled iodoacetamide into MG2 was obtained with or without prior
      reduction. When radiolabelled alkylated MG2 was digested with Endoproteinase Lys
      C and the derived peptides were separated by reversed-phase high-performance
      liquid chromatography (RP-HPLC), radioactivity was found in two fractions. Mass
      spectral analyses of these fractions showed the presence of peptides Cys-Leu-His
      Lys and Arg-Cys-Arg-Pro-Lys, both containing carboxymethylated cysteines. These
      results show that the cysteines in the structural motif associated with bacterial
      binding exist in the dithiol form, and suggest the potential use of cysteine
      containing peptides as agents to modify interactions of MG2 with microbes and
      oral surfaces.

PMID- 12221018
TI  - Action potentials and twitch forces of rabbit masseter motor units at optimum jaw
      angle.
AB  - This study examines mutual correlations between electrical and contractile motor
      unit properties. Action potentials and twitch force responses of 42 masseter
      motor units were recorded in 14 rabbits. Motor units were excited by stimulating
      motoneurones in the trigeminal motor nucleus. Action potentials and twitches were
      measured at different jaw gapes between 0 and 21 degrees, in steps of 3 degrees.
      For each motor unit, the jaw angle-active force interrelation was determined and
      variables for action potential and force were compared at the jaw angle at which
      the motor unit produced the largest force. The results showed a large variation
      in variables for action potential and force, possibly related to the variation in
      motor-unit morphology. A weak correlation was found between the variables for
      action-potential amplitude and the magnitude of optimum force, indicating that
      motor units producing larger forces tended to have action potentials with larger
      amplitudes. Twitch-contraction time and the moment arm of the motor unit
      correlated positively with both the median frequency and the duration of the
      action potential. This indicates that slower contracting motor units had longer
      action potentials and is in accord with the earlier observation that slower motor
      units are preferentially located in the anterior regions of the masseter.

PMID- 12221017
TI  - Changes in periodontal pulsation in relation to increasing loads on rat molars
      and to blood pressure.
AB  - Pulsation originating from the vascular system of the periodontal ligament (PDL)
      is apparently synchronized with the heartbeat. As periodontal pulsation causes
      pulsatile tooth vibration, it might be possible to evaluate it indirectly by
      measuring tooth vibration. Periodontal pulsation has been found to be dependent
      on blood flow and blood pressure in the PDL. Heavy orthodontic force is known to
      reduce blood flow and decrease the amplitude of the pulsation. The purpose now
      was to examine (1). the magnitude of the experimental orthodontic force that will
      impair PDL blood flow; and (2). the differences in the amplitude of pulsation
      between normal and hypertensive animals. The experiments were performed on 10
      Wistar, 10 Dahl S and 10 Dahl R rats. Hypertension was induced in Dahl S rats.
      The head and maxilla of anaesthetized animals were immobilized. Mesial tipping
      forces of different loads (0.098-0.882 N) were applied to a molar and periodontal
      pulsation was measured with a highly sensitive laser displacement meter. The
      periodontal pulsation at each load resembled a blood-volume pulse wave. Its
      amplitude began to decrease at a load of 0.588 N in Wistar and Dahl R rats, and
      at 0.784 N in Dahl S rats. The group with induced hypertension had a
      significantly larger amplitude than the other two groups when 0.588 N was
      applied. These results suggest that: (1). periodontal pulsation can indicate a
      PDL overload; and (2). that systemic blood pressure affects the amplitude of
      periodontal pulsation during loading.

PMID- 12221019
TI  - Enhanced neutrophil emigration and Porphyromonas gingivalis reduction following
      PGG-glucan treatment of mice.
AB  - Periodontal disease is the consequence of a mixed Gram-negative infection in the
      gingival sulcus and has been associated with deficits in the neutrophil response.
      A novel, and heretofore untested, alternative approach to therapy is the use of
      biological-response modulators that enhance the neutrophil response. Poly-beta1-6
      glucotriosyl-beta1-3-glucopyranose glucan (PGG-glucan) is an immunomodulator,
      derived from yeast, which specifically enhances neutrophil priming, phagocytosis
      and bacterial killing while failing to induce inflammatory cytokine expression.
      The hypothesis tested was that PGG-glucan could enhance host resistance to a Gram
      negative periodontal pathogen, Porphyromonas gingivalis. Chambers were implanted
      subcutaneously in the dorsolumbar region of C57BL/6J mice and allowed to heal for
      14 days. PGG-glucan was administered subcutaneously to one-half of the animals
      and saline to the other half. In the first set of experiments the chambers were
      inoculated with P. gingivalis (A7436) at 4 x 10 (6), 4 x 10 (7), and 4 x 10 (8)
      colony-forming units (CFU). In the second set of experiments the chambers were
      inoculated with 5 x 10 (8) CFU of either P. gingivalis or Streptococcus sanguis,
      a Gram-positive oral microbe that is not periodontopathic. Chambers were sampled
      over the following 2 weeks. The results demonstrated that: (1). bacterial CFU and
      neutrophils increased with increasing bacterial inoculum (P<0.02); (2). bacterial
      CFU were lower in the PGG-glucan-treated animals than in the saline controls
      (P<0.02); and (3). neutrophil counts were higher in the PGG-glucan-treated
      animals than in the saline controls (P<0.01). These results indicate that PGG
      glucan significantly enhances neutrophil emigration and bacterial killing, thus
      decreasing the bacterial infection in this model system.

PMID- 12221020
TI  - Dental eruption and exfoliation chronology in the ferret (Mustela putorius furo).
AB  - Substituting ferrets for rats and dogs as animal models for craniofacial research
      is favourable because of the similarity of many of the ferret's anatomical,
      metabolic and physiological features to those of man. Other advantages are cost
      effectiveness and possibly less ethical controversy. However, information on the
      dental chronology of ferrets needs to be supplemented if this animal is to be
      promoted as an alternative model. Dental development was here examined in 16
      ferrets (eight males, eight females) from three litters at between 12 and 90 days
      of age. Dental eruption and exfoliation were assessed and recorded every second
      day. The sequence of eruption of deciduous and permanent teeth was determined and
      data were analysed statistically. Also, any sex-related differences in eruption
      and exfoliation ages were defined. No deciduous incisors were observed to erupt
      in this group of animals. Other deciduous teeth erupted between the 19th and 31st
      postnatal days, and exfoliated between days 51 and 76. The time of eruption of
      the permanent teeth ranged from 42 to 77 days, in accordance with the stage of
      the mixed dentition. The female ferrets were generally ahead of the males in the
      exfoliation age of their deciduous teeth and the eruption age of their permanent
      teeth, but this, a sex difference did not apply to the eruption age of the
      deciduous teeth. These extended basic data might facilitate the introduction of
      this alternative experimental animal into craniofacial research.

PMID- 12221023
TI  - Reducing young driver crash risk.

PMID- 12221021
TI  - An immunohistochemical study of the effects of pulsed neodymium:yttrium-aluminium
      garnet laser irradiation in root canals on the eruption of rat incisors.
AB  - The incisors of 21 Wistar rats were transected, pulp tissue was extirpated for
      10mm from the level of the gingival margin and each canal was prepared with
      files. The fibre tip of a pulsed neodymium:yttrium-aluminium-garnet laser was
      inserted into the root canal for 10mm and laser irradiation delivered at 2 W and
      20 pulses/s for 10s. After 6 weeks the mandibles were removed and sectioned.
      Sections were stained either with haematoxylin and eosin or immunohistochemically
      using polyclonal antibodies against keratin/cytokeratin, amelogenin and type I
      collagen. The inner epithelial cells on the labial side differentiated into
      ameloblasts in animals where eruption had recovered. The pulp cells
      differentiated into odontoblast-like cells and staining for type I collagen was
      evident in pulp cells, odontoblast-like cells and inside dentinal tubules. In
      animals where eruption had ceased, the inner epithelial cells on the labial side
      did not differentiate into ameloblasts. Staining for type I collagen was observed
      in the mineralized nodules and tubules of dentine-like hard tissues in the pulp
      cavity. These results suggest that differentiation of epithelial cells on the
      labial side into ameloblasts is involved in the re-eruption process.

PMID- 12221024
TI  - The safety value of driver education and training.
AB  - BACKGROUND: New drivers, especially young ones, have extremely high crash rates.
      Formal instruction, which includes in-class education and in-vehicle training,
      has been used as a means to address this problem. OBJECTIVES: To summarize the
      evidence on the safety value of such programs and suggest improvements in program
      delivery and content that may produce safety benefits. METHODS: The empirical
      evidence was reviewed and summarized to determine if formal instruction has been
      shown to produce reductions in collisions, and to identify ways it might achieve
      this objective. RESULTS: The international literature provides little support for
      the hypothesis that formal driver instruction is an effective safety measure. It
      is argued that such an outcome is not entirely unexpected given that traditional
      programs fail to address adequately the age and experience related factors that
      render young drivers at increased risk of collision. CONCLUSIONS:
      Education/training programs might prove to be effective in reducing collisions if
      they are more empirically based, addressing critical age and experience related
      factors. At the same time, more research into the behaviors and crash experiences
      of novice drivers is needed to refine our understanding of the problem.

PMID- 12221025
TI  - Rationale for graduated licensing and the risks it should address.
AB  - The increased crash risk of young, beginning drivers has long been cause for
      concern. Graduated licensing systems, which seek to phase in driving experience
      gradually over time, have recently been adopted by many states in an effort to
      reduce these risks. In an attempt to define the basic rationale for graduated
      licensing, relevant research evidence that describes the conditions under which
      risk is known to be increased for young drivers was reviewed. Potential changes
      in licensing laws that best address these known risk factors are described. It
      was found that certain situations contribute to even greater crash risk, most
      notably nighttime driving and driving with passengers in the peer group. The
      underlying premise for graduated licensing is that while crash risk of young
      drivers is heightened under all situations, some situations are more or less
      risky than others. If experience can be gained initially under lower risk
      conditions, both in the learning stage and when first licensed, crash risk will
      be reduced.

PMID- 12221026
TI  - Developmental sources of crash risk in young drivers.
AB  - OBJECTIVE: To outline various sources of crash risk among young drivers that are
      developmental (age based) factors. METHODS AND RESULTS: First, a distinction is
      made between adolescence (ages 10-18) and emerging adulthood (ages 18-25) in
      order to shed light on the reasons for especially high crash rates among 16-17
      year old drivers relative to 18-25 year olds. Then various developmental sources
      of risk in adolescence are described, including the power of friends, the
      optimistic bias, and adolescent emotionality. The reasons for especially high
      crash rates among young males are discussed, with an emphasis on how American
      ideas about manhood promote driving risks. Finally, a cross national comparison
      between adolescents in the United States and Denmark shows how developmental
      risks interact with driving policies. CONCLUSIONS: The high crash rates of
      adolescents relative to emerging adults and of emerging adults relative to older
      drivers can be explained in part by developmental factors.

PMID- 12221027
TI  - Promoting parental management of teen driving.
AB  - OBJECTIVE: Parenting may be an important protective factor against teen driving
      risk; however, parents do not limit teen driving as much as might be expected.
      The Checkpoint Program was designed to promote parental management of teen
      driving through the use of staged persuasive communications. METHODS: Parent-teen
      dyads (n = 452) were recruited when teens received learner's permits and
      interviewed over the telephone at baseline, licensure, and three months post
      licensure. After baseline, families were randomized to either the intervention
      group that received persuasive communications or to the comparison group that
      received general information about driving safety. RESULTS: Both parents and
      teens in the intervention group reported significantly greater limits on teen
      driving at licensure and three months post-licensure. In multivariate analyses,
      intervention and baseline driving expectations had significant effects on driving
      limits at licensure. Intervention and driving limits established at licensure
      were associated with three month driving limits. CONCLUSION: The findings
      indicate that exposure to the Checkpoints Program increased parental limits on
      teen driving.

PMID- 12221028
TI  - Graduated driver licensing: what works?
AB  - BACKGROUND: Graduated driver licensing (GDL) adds an intermediate stage to driver
      licensing between the learner permit and full licensure stages that is intended
      to ameliorate the high risk of novice drivers. OBJECTIVES: To assess the
      contribution of various elements of GDL to reduction in the crash rates of young
      novice drivers. METHODS: An extensive review of the literature was undertaken to
      synthesise research findings on crash reduction. RESULTS: Increasing the length
      of the learner period and the amount practice required has reduced crash risk,
      partly through improved performance and partly by delaying licensure. Intervening
      early with traffic violators and making full licensure dependent on a clean
      driving record provide both general and specific deterrents to unsafe driving.
      Restrictions on night driving and carrying passengers are effective in reducing
      the increased risk of these situations. The benefits of multistage instruction
      and testing as well as the use of visible tags to identify novices have not as
      yet been adequately evaluated. CONCLUSIONS: While graduated driver licensing has
      proven a generally effective means of reducing the crash risk of novice drivers,
      controlled research is needed to assess the benefits of its individual
      components.

PMID- 12221029
TI  - Guidelines for colorectal cancer screening in high risk groups.
AB  - The British Society of Gastroenterology (BSG) and the Association of
      Coloproctology for Great Britain and Ireland (ACPGBI) commissioned these
      guidelines. The aim is to provide guidance on the appropriateness, method, and
      frequency of screening people with diseases known to be associated with
      colorectal cancer. There is increasing awareness among relatives of patients with
      colorectal cancer that they may be at risk from this disease and there is rising
      demand for screening. These guidelines are for members of gastroenterology teams,
      primary care physicians, purchasers of health care, and people thought to be at
      increased risk of colorectal cancer.

PMID- 12221030
TI  - Guidelines for follow up after resection of colorectal cancer.

PMID- 12221031
TI  - Surveillance guidelines after removal of colorectal adenomatous polyps.

PMID- 12221032
TI  - Guidelines for screening and surveillance of asymptomatic colorectal cancer in
      patients with inflammatory bowel disease.

PMID- 12221033
TI  - Screening guidelines for colorectal cancer and polyps in patients with
      acromegaly.

PMID- 12221034
TI  - Guidelines for monitoring of patients with ureterosigmoidostomy.

PMID- 12221035
TI  - Guidance on large bowel surveillance for people with two first degree relatives
      with colorectal cancer or one first degree relative diagnosed with colorectal
      cancer under 45 years.

PMID- 12221036
TI  - Guidance on gastrointestinal surveillance for hereditary non-polyposis colorectal
      cancer, familial adenomatous polypolis, juvenile polyposis, and Peutz-Jeghers
      syndrome.

PMID- 12221038
TI  - Population-level effects of pesticides and other toxicants on arthropods.
AB  - New developments in ecotoxicology are changing the way pesticides and other
      toxicants are evaluated. An emphasis on life histories and population fitness
      through the use of demography, other measures of population growth rate, field
      studies, and modeling are being exploited to derive better estimates of pesticide
      impacts on both target and nontarget species than traditional lethal dose
      estimates. We review the state of the art in demographic toxicology, an approach
      to the evaluation of toxicity that uses life history parameters and other
      measures of population growth rate. A review of the literature revealed that 75
      studies on the use of demography and similar measures of population growth rate
      in toxicology have been published since 1962. Of these 75 studies, the majority
      involved arthropods. Recent evaluations have indicated that ecotoxicological
      analysis based on population growth rate results in more accurate assessments of
      the impacts of pesticides and other toxicants because measures of population
      growth rate combine lethal and sublethal effects, which lethal dose/concentration
      estimates (LD/LC50) cannot do. We contend that to advance our knowledge of
      toxicant impacts on arthropods, the population growth rate approach should be
      widely adopted.

PMID- 12221039
TI  - The evolution of alternative genetic systems in insects.
AB  - There are three major classes of insect genetic systems: those with diploid males
      (diplodiploidy), those with effectively haploid males (haplodiploidy), and those
      without males (thelytoky). Mixed systems, involving cyclic or facultative
      switching between thelytoky and either of the other systems, also occur. I
      present a classification of the genetic systems of insects and estimate the
      number of evolutionary transitions between them that have occurred. Obligate
      thelytoky has arisen from each of the other systems, and there is evidence that
      over 900 such origins have occurred. The number of origins of facultative
      thelytoky and the number of reversions from obligate thelytoky to facultative and
      cyclic thelytoky are difficult to estimate. The other transitions are few in
      number: five origins of cyclic thelytoky, eight origins of obligate haplodiploidy
      (including paternal genome elimination), the strange case of Micromalthus, and
      the two reversions from haplodiploidy to diplodiploidy in scale insects.
      Available evidence tends to support W.D. Hamilton's hypothesis that maternally
      transmitted endosymbionts have been involved in the origins of haplodiploidy.
      Bizarre systems of extrazygotic inheritance in Sternorrhyncha are not easily
      accommodated into any existing classification of genetic systems.

PMID- 12221041
TI  - Giant molecule titin and myocardial stiffness.

PMID- 12221042
TI  - Mitral valve prolapse prevalence and complications: an ongoing dialogue.

PMID- 12221043
TI  - Clinical assessment of atherosclerotic lesions: emerging from angiographic
      shadows.

PMID- 12221044
TI  - Aortic root dilatation after repair of tetralogy of Fallot: pathology from the
      past?

PMID- 12221045
TI  - Contemporary evaluation and management of hypertrophic cardiomyopathy.

PMID- 12221046
TI  - Electroanatomic mapping and catheter ablation of breakthroughs from the right
      atrium to the superior vena cava in patients with atrial fibrillation.
AB  - BACKGROUND: The superior vena cava (SVC) is one of the sources of ectopies that
      can initiate atrial fibrillation (AF). We investigated by radiofrequency ablation
      the electrophysiological characteristics of the junction of the right atrium (RA)
      and the SVC and the feasibility of electrical disconnection of the SVC from the
      RA. METHODS AND RESULTS: Sixteen patients with paroxysmal AF after pulmonary vein
      isolation underwent electroanatomic mapping at the RA-SVC junction during sinus
      rhythm. Mapping showed sharp potentials (SVC potentials) inside the SVC.
      Activation spread from the earliest SVC potential (breakthrough) to the rest of
      the SVC. SVC potentials were found over a large amount of the circumference,
      suggesting widespread muscle coverage of the SVC. Breakthroughs from the RA to
      SVC were located anteriorly, laterally, posteriorly, and septally in 3, 4, 10,
      and 6 patients, respectively. The number of breakthroughs was 1.4+/-0.5 per
      patient. Radiofrequency energy was applied with the end point of electrical
      disconnection. All breakthroughs were eliminated with 3.1+/-1.7 applications per
      breakthrough without complications. CONCLUSIONS: SVC potentials can be recorded
      inside the SVC. There are specific breakthroughs from the RA to the SVC that can
      be identified by electroanatomic mapping. The electrical disconnection of the SVC
      from the RA is feasible.

PMID- 12221047
TI  - Identification of genetic variants in endothelial lipase in persons with elevated
      high-density lipoprotein cholesterol.
AB  - BACKGROUND: Elevated high-density lipoprotein cholesterol (HDL-C) is associated
      with reduced risk of cardiovascular disease, and variation in HDL-C levels has
      been shown to be approximately 50% heritable. Overexpression of endothelial
      lipase (EL), a member of the lipoprotein lipase gene family, markedly reduces HDL
      C levels in mouse models. We hypothesized that genetic variation in EL might be
      associated with elevated HDL-C. METHODS AND RESULTS: All exons and 1.2 kilobase
      of promoter of the EL gene were sequenced in 20 unrelated human subjects with
      high HDL-C levels. A total of 17 variants were identified. Six of these were
      potentially functional and were confirmed by restriction enzyme analysis. Four
      variants result in amino acid changes (Gly26Ser, Thr111Ile, Thr298Ser, and
      Asn396Ser,) and 2 variants were in the promoter (-303A/C and -410C/G). The
      genotype frequencies of each variant were determined in 176 black controls, 165
      white controls, and 123 whites with high HDL-C. The Thr111Ile variant was the
      most common, with an allele frequency of 10.3% in blacks, 31.2% in white
      controls, and 32.6% in the high HDL-C group. The remaining variants all had
      allele frequencies <5.0% but differed in frequency among the 3 groups.
      Interestingly, Gly26Ser, Thr298Ser, and -303A/C were found in the black and high
      HDL-C white cohorts but were absent in the control white group. CONCLUSIONS: Six
      new potentially functional variants in EL were discovered through sequencing of
      the EL gene in subjects with high HDL-C levels. Differences in allele frequencies
      exist between blacks and whites and between control subjects and those with high
      HDL-C levels.

PMID- 12221048
TI  - Dose response of almonds on coronary heart disease risk factors: blood lipids,
      oxidized low-density lipoproteins, lipoprotein(a), homocysteine, and pulmonary
      nitric oxide: a randomized, controlled, crossover trial.
AB  - BACKGROUND: Although recent studies have indicated that nut consumption may
      improve levels of blood lipids, nuts are not generally recommended as snacks for
      hyperlipidemic subjects because of their high fat content. Furthermore, the
      effective dose is still unknown. METHODS AND RESULTS: The dose-response effects
      of whole almonds, taken as snacks, were compared with low-saturated fat (<5%
      energy) whole-wheat muffins (control) in the therapeutic diets of hyperlipidemic
      subjects. In a randomized crossover study, 27 hyperlipidemic men and women
      consumed 3 isoenergetic (mean 423 kcal/d) supplements each for 1 month.
      Supplements provided 22.2% of energy and consisted of full-dose almonds (73+/-3
      g/d), half-dose almonds plus half-dose muffins, and full-dose muffins. Fasting
      blood, expired air, blood pressure, and body weight measurements were obtained at
      weeks 0, 2, and 4. Mean body weights differed <300 g between treatments. The full
      dose almonds produced the greatest reduction in levels of blood lipids.
      Significant reductions from baseline were seen on both half- and full-dose
      almonds for LDL cholesterol (4.4+/-1.7%, P=0.018, and 9.4+/-1.9%, P<0.001,
      respectively) and LDL:HDL cholesterol (7.8+/-2.2%, P=0.001, and 12.0+/-2.1%,
      P<0.001, respectively) and on full-dose almonds alone for lipoprotein(a) (7.8+/
      3.5%, P=0.034) and oxidized LDL concentrations (14.0+/-3.8%, P<0.001), with no
      significant reductions on the control diet. No difference was seen in pulmonary
      nitric oxide between treatments. CONCLUSIONS: Almonds used as snacks in the diets
      of hyperlipidemic subjects significantly reduce coronary heart disease risk
      factors, probably in part because of the nonfat (protein and fiber) and
      monounsaturated fatty acid components of the nut.

PMID- 12221049
TI  - Titin isoform switch in ischemic human heart disease.
AB  - BACKGROUND: Ischemia-induced cardiomyopathy usually is accompanied by elevated
      left ventricular end-diastolic pressure, which follows from increased myocardial
      stiffness resulting from upregulated collagen expression. In addition to
      collagen, a main determinant of stiffness is titin, whose role in ischemia
      induced left ventricular stiffening was studied here. Human heart sarcomeres
      coexpress 2 principal titin isoforms, a more compliant N2BA isoform and a stiffer
      N2B isoform. In comparison, normal rat hearts express almost no N2BA titin.
      METHODS AND RESULTS: Gel electrophoresis and immunoblotting were used to
      determine the N2BA-to-N2B titin isoform ratio in nonischemic human hearts and
      nonnecrotic left ventricle of coronary artery disease (CAD) patients. The average
      N2BA-to-N2B ratio was 47:53 in severely diseased CAD transplanted hearts and
      32:68 in nonischemic transplants. In normal donor hearts and donor hearts with
      CAD background, relative N2BA titin content was approximately 30%. The titin
      isoform shift in CAD transplant hearts coincided with a high degree of
      modifications of cardiac troponin I, probably indicating increased preload.
      Immunofluorescence microscopy on CAD transplant specimens showed a regular cross
      striated arrangement of titin and increased expression of collagen and desmin.
      Force measurements on isolated myofibrils revealed reduced passive-tension levels
      in sarcomeres of CAD hearts with high left ventricular end-diastolic pressure
      compared with sarcomeres of normal hearts. In a rat model of ischemia-induced
      myocardial infarction (left anterior descending coronary artery ligature), 43% of
      animals, but only 14% of sham-operated animals, showed a distinct N2BA titin band
      on gels. CONCLUSIONS: A titin isoform switch was observed in chronically ischemic
      human hearts showing extensive remodeling, which necessitated cardiac
      transplantation. The shift, also confirmed in rat hearts, caused reduced titin
      derived myofibrillar stiffness. Titin modifications in long-term ischemic
      myocardium could impair the ability of the heart to use the Frank-Starling
      mechanism.

PMID- 12221050
TI  - Contribution of exercise-induced mitral regurgitation to exercise stroke volume
      and exercise capacity in patients with left ventricular systolic dysfunction.
AB  - BACKGROUND: Functional mitral regurgitation (MR) is common in patients with heart
      failure and left ventricular (LV) dysfunction, and its severity may vary over
      time, depending primarily on the loading conditions. Because dynamic changes in
      the severity of functional MR may affect forward stroke volume, we hypothesized
      that exercise-induced changes in MR severity influence the stroke volume response
      of patients with LV dysfunction to exercise, and hence their exercise capacity.
      METHODS AND RESULTS: Heart failure patients (n=25; mean age 53+/-12 years) with
      LV dysfunction underwent dynamic bicycle exercise at steady-state levels of 30%,
      60%, and 90% of predetermined peak VO2. During each exercise level, right heart
      pressures, cardiac output, VO2, and MR severity were measured simultaneously.
      During exercise, MR severity, as evaluated by the ratio of MR jet over left
      atrium area, increased from 15+/-8% to 33+/-15%. Peak VO2, exercise-induced
      changes in stroke volume, and those in capillary wedge pressure correlated with
      the changes in MR (r=-0.55, -0.87, and 0.62, respectively, P<0.01). The changes
      in MR severity also correlated with those in end-diastolic (r=-0.75, P<0.01) and
      end-systolic (r=-0.72, P<0.01) sphericity indexes and those in the coaptation
      distance (r=0.86, P<0.01). CONCLUSIONS: Our data indicate that in patients with
      LV dysfunction, exercise-induced changes in MR severity limit the stroke volume
      adaptation during exercise and therefore contribute to limitation of exercise
      capacity.

PMID- 12221051
TI  - Aging and forearm postjunctional alpha-adrenergic vasoconstriction in healthy
      men.
AB  - BACKGROUND: Muscle sympathetic vasoconstrictor nerve activity increases with age
      in healthy humans but does not result in an augmented forearm vasoconstrictor
      tone. We tested the hypothesis that this is due to a reduction in postjunctional
      alpha-adrenergic responsiveness to endogenous norepinephrine (NE) release and
      determined whether this was specific to alpha1- or alpha2-adrenergic receptors.
      METHODS AND RESULTS: Forearm blood flow (FBF, by strain-gauge plethysmography)
      responses to local intra-arterial infusions of tyramine (which evokes endogenous
      NE release), phenylephrine (selective alpha1-agonist), and clonidine (alpha2
      agonist) were determined in 10 young (aged 26+/-1 [mean+/-SEM] years) and 10
      older (aged 65+/-1 years) healthy normotensive men after local beta-adrenergic
      blockade with propranolol. Basal forearm vascular tone was not different in young
      men and older men. The percentage reduction in FBF in response to the highest
      dose of tyramine was blunted in older men compared with young men (-37+/-3%
      versus -49+/-3%, respectively; P<0.01) despite a greater increase in deep venous
      NE concentration in older men (910+/-103 versus 565+/-69 pg/mL, respectively;
      P<0.001). Maximal reductions in FBF to phenylephrine were also blunted in older
      men (-47+/-2% versus -58+/-3% in young men, P<0.05). In contrast, the reductions
      in FBF (-36+/-7% versus -40+/-3% for older versus young men, respectively) and
      also in venous NE concentration (-79+/-24 versus -84+/-13 pg/mL for older versus
      young men, respectively) to clonidine were similar in the 2 groups. Finally,
      forearm sympathetic alpha-adrenergic vasoconstrictor tone (assessed via
      nonselective alpha-blockade with phentolamine) was significantly lower in older
      men. CONCLUSIONS: Our results indicate that human aging is associated with a
      reduction in forearm postjunctional alpha-adrenergic responsiveness to endogenous
      NE release and that this might be specific to alpha1-adrenergic receptors.
      Furthermore, the contribution of sympathetic alpha-adrenergic vasoconstriction to
      basal forearm vascular tone is reduced with age in healthy men.

PMID- 12221052
TI  - Natural history of asymptomatic mitral valve prolapse in the community.
AB  - BACKGROUND: The outcome of mitral valve prolapse (MVP) is controversial, with
      marked discrepancies in reported complication rates. METHODS AND RESULTS: We
      conducted a community study of all Olmsted County, Minn, residents first
      diagnosed with asymptomatic MVP between 1989 and 1998 (N=833). Diagnosis,
      motivated by auscultatory findings (n=557) or incidental (n=276), was always
      confirmed by echocardiography with the use of current criteria. End points
      analyzed during 4581 person-years of follow-up were mortality (n=96, 19+/-2% at
      10 years), cardiovascular morbidity (n=171), and MVP-related events (n=109, 20+/
      2% at 10 years). The most frequent primary risk factors for cardiovascular
      mortality were mitral regurgitation from moderate to severe (P=0.002, n=131) and,
      less frequently, ejection fraction <50% (P=0.003, n=31). Secondary risk factors
      independently predictive of cardiovascular morbidity were slight mitral
      regurgitation, left atrium > or =40 mm, flail leaflet, atrial fibrillation, and
      age > or =50 years (all P<0.01). Patients with only 0 or 1 secondary risk factor
      (n=430) had excellent outcome, with 10-year mortality of 5+/-2% (P=0.17 versus
      expected), cardiovascular morbidity of 0.5%/y, and MVP-related events of 0.2%/y.
      Patients with > or =2 secondary risk factors (n=250) had mortality similar to
      expected (P=0.20) but high cardiovascular morbidity (6.2%/y, P<0.01) and notable
      MVP-related events (1.7%/y, P<0.01). Patients with primary risk factors (n=153)
      showed excess 10-year mortality (45+/-9%, P=0.01 versus expected), high morbidity
      (18.5%/y, P<0.01), and high MVP-related events (15%/y, P<0.01). CONCLUSIONS:
      Natural history of asymptomatic MVP in the community is widely heterogeneous and
      may be severe. Clinical and echocardiographic characteristics allow separation of
      the majority of patients with excellent prognosis from subsets of patients
      displaying, during follow-up, high morbidity or even excess mortality as direct a
      consequence of MVP.

PMID- 12221053
TI  - Coronary sinus-ventricular accessory connections producing posteroseptal and left
      posterior accessory pathways: incidence and electrophysiological identification.
AB  - BACKGROUND: The coronary sinus (CS) has a myocardial coat (CSMC) with extensive
      connections to the left and right atria. We postulated that some posteroseptal
      and left posterior accessory pathways (CSAPs) result from connections between a
      cuff of CSMC extending along the middle cardiac vein (MCV) or posterior coronary
      vein (PCV) and the ventricle. The purpose of the present study was to use CS
      angiography and mapping to define and determine the incidence of CSAPs and
      determine the relationship to CS anatomy. METHODS AND RESULTS: CSAP was defined
      by accessory pathway (AP) potential or earliest activation in the MCV or PCV and
      late activation at anular endocardial sites. A CSAP was identified in 171 of 480
      patients undergoing ablation of a posteroseptal or left posterior AP. CS
      angiography revealed a CS diverticulum in 36 (21%) and fusiform or bulbous
      enlargement of the small cardiac vein, MCV, or CS in 15 (9%) patients. The
      remaining 120 (70%) patients had an angiographically normal CS. A CSMC extension
      potential (CSE), like an AP potential, was recorded in the MCV in 98 (82%), in
      the PCV in 13 (11%), in both the MCV and PCV in 6 (5%), and in the CS in 3 (2%)
      of 120 patients. CSMC potentials were recorded between the timing of atrial and
      CSE potentials. CONCLUSIONS: CSAPs result from a connection between a CSMC
      extension (along the MCV or PCV) and the ventricle. The CS is angiographically
      normal in most patients.

PMID- 12221054
TI  - Classification of human carotid atherosclerotic lesions with in vivo
      multicontrast magnetic resonance imaging.
AB  - BACKGROUND: Recent studies demonstrated that in vivo and ex vivo MRI can
      characterize the components of the carotid atherosclerotic plaque, such as
      fibrous tissue, lipid/necrotic core, calcium, hemorrhage, and thrombus. The
      purpose of this study was to determine whether in vivo high-resolution
      multicontrast MRI could accurately classify human carotid atherosclerotic plaque
      according to the American Heart Association classification. METHODS AND RESULTS:
      Sixty consecutive patients (mean age 70 years; 54 males) scheduled for carotid
      endarterectomy were imaged with a 1.5-T scanner after informed consent was
      obtained. A standardized protocol was used to obtain 4 different contrast
      weighted images (time of flight and T1-, PD-, and T2-weighted) of the carotid
      arteries. Best voxel size was 0.25x0.25x1 mm3. Carotid plaques were removed
      intact and processed for histological examination. Both MR images and
      histological sections were independently reviewed, categorized, and compared.
      Overall, the classification obtained by MRI and the American Heart Association
      classifications showed good agreement, with Cohen's kappa (95% CI) of 0.74 (0.67
      to 0.82) and weighted kappa of 0.79. The sensitivity and specificity,
      respectively, of MRI classification were as follows: type I-II lesions, 67% and
      100%; type III lesions, 81% and 98%; type IV-V lesions, 84% and 90%; type VI
      lesions, 82% and 91%; type VII lesions, 80% and 94%; and type VIII lesions, 56%
      and 100%. CONCLUSIONS: In vivo high-resolution multicontrast MRI is capable of
      classifying intermediate to advanced atherosclerotic lesions in the human carotid
      artery and is also capable of distinguishing advanced lesions from early and
      intermediate atherosclerotic plaque.

PMID- 12221055
TI  - Progressive aortic root dilatation in adults late after repair of tetralogy of
      Fallot.
AB  - BACKGROUND: Aortic valve or aortic root (AoRo) replacement is occasionally
      required because of AoRo dilatation and aortic regurgitation (AR) in repaired
      tetralogy of Fallot (TOF). We evaluated AoRo size and possible factors associated
      with its dynamic nature in adults with repaired TOF. METHODS AND RESULTS: Of 216
      patients with TOF repair who underwent echocardiography in 1997, we identified 32
      patients (mean age, 36+/-8.0 years) with AoRo dilatation, defined as ratio of
      observed to expected AoRo size by standard nomogram >1.5 (group A), and 54 TOF
      controls, matched for age with AoRo ratio <1.5 (group B), who underwent at least
      1 previous echocardiogram in the preceding 10 years. Mean indexed AoRo size
      (cm/m2) in 1997 was 2.5+/-0.5 in group A and 1.7+/-0.2 in group B (P<0.0001).
      AoRo rate of change (mm/year) from the first to 1997 study (mean interval, 5.2+/
      3.8 years) was 1.7+/-3.8 in group A and 0.03+/-1.6 in group B (P=0.001). Patients
      from group A had a longer shunt-to-repair interval (P=0.048) with a higher
      prevalence of pulmonary atresia (P<0.0001), right aortic arch (P=0.03), moderate
      to severe AR (P=0.002), aortic valve replacement (P=0.02), larger cardiothoracic
      ratio (P=0.02), and increased left ventricular end-diastolic dimensions
      (P=0.002). CONCLUSIONS: A subset of adult TOF exhibits ongoing dilatation of AoRo
      late after repair. This dilatation relates to previous long-standing volume
      overload of AoRo and possibly to intrinsic properties of AoRo and may lead to AR.
      Meticulous follow-up of AoRo after TOF repair is recommended.

PMID- 12221056
TI  - Increased tissue factor expression predicts development of cardiac allograft
      vasculopathy.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) limits the long-term success of
      cardiac transplantation. The incidence of CAV is increased in patients with
      elevated plasma levels of oxidized lipids or fibrin deposition within right heart
      biopsy (RHB) specimens. The present study investigated whether tissue factor
      (TF), the expression of which is regulated by oxidized lipids, is upregulated in
      patients with CAV. METHODS AND RESULTS: A TF score was developed to quantify TF
      expression in RHB specimens from 63 consecutive patients undergoing routine
      annual posttransplantation RHB and coronary angiography. In patients >2 years
      (3.0+/-0.8 years) posttransplantation (n=35), a high TF score was observed with
      greater frequency (75% versus 26%, P<0.004) in patients with CAV than those
      without CAV. In patients <2 years (0.87+/-0.48 years) posttransplantation (n=28)
      without evidence of CAV, the TF score was determined and patients were followed
      up prospectively. A high TF score had a positive predictive value of 78.6% for
      the development of CAV, and a low TF score had a negative predictive value of
      100%. CONCLUSIONS: These data demonstrate that early TF expression predicts
      subsequent development of CAV. Increased TF expression could link the elevated
      levels of oxidized LDL and fibrin deposition known to precede CAV. These findings
      suggest that TF may play a role in the pathophysiology of CAV and could offer a
      potential prognostic tool and a novel target for the prevention of CAV, possibly
      with antioxidants or inhibitors of the TF pathway.

PMID- 12221057
TI  - Changes in titin isoform expression in pacing-induced cardiac failure give rise
      to increased passive muscle stiffness.
AB  - BACKGROUND: Titin contains a molecular spring segment that underlies passive
      myocardial stiffness. Myocardium coexpresses titin isoforms with molecular spring
      length variants and, consequently, distinct stiffness characteristics: the stiff
      N2B isoform (short spring) and more compliant N2BA isoform (long spring). We
      tested whether changes in titin isoform expression occur in the diastolic
      dysfunction that accompanies heart failure. METHODS AND RESULTS: We used the
      tachycardia-induced dilated cardiomyopathy canine model (4-week pacing) and found
      that control myocardium coexpresses the N2B and N2BA isoforms at similar levels,
      whereas in dilated cardiomyopathy the expression ratio had shifted, without
      affecting the amount of total titin, toward more prominent N2B expression. This
      shift was accompanied by elevated titin-based passive muscle stiffness. Pacing
      also resulted in significant upregulation of obscurin, an approximately 800-kDa
      elastic protein with several signaling domains. CONCLUSIONS: Coexpression of
      titin isoforms with distinct mechanical properties allows modulation of passive
      stiffness via adjustment of the isoform expression ratio. The canine pacing
      induced heart failure model uses this mechanism to increase myocardial stiffness.
      Thus, changes in titin isoform expression may play a role in diastolic
      dysfunction in heart failure.

PMID- 12221058
TI  - Lipid lowering reduces oxidative stress and endothelial cell activation in rabbit
      atheroma.
AB  - BACKGROUND: Lipid lowering may reduce acute coronary events in patients in part
      by reducing vascular inflammation. Oxidative stress induces endothelial cell (EC)
      expression of vascular cell adhesion molecule 1 (VCAM-1) and monocyte
      chemoattractant protein 1 (MCP-1) and reduces levels of atheroprotective NO,
      leading to monocyte recruitment and macrophage accumulation. This study tested
      the hypothesis that lipid lowering decreases oxidative stress and improves EC
      functions related to inflammatory cell accumulation. METHODS AND RESULTS: Rabbits
      consumed an atherogenic diet for 4 months to produce atheroma, followed by a
      purified chow diet for 16 months. Atherosclerotic aortas from
      hypercholesterolemic rabbits produced high levels of reactive oxygen species.
      Oxidized LDL (oxLDL) accumulated in atheroma underlying ECs that overexpress VCAM
      1. In contrast, few if any ECs in atheroma stained for endothelial NO synthase
      (eNOS). Lipid lowering reduced reactive oxygen species production, oxLDL
      accumulation, and plasma levels of anti-oxLDL IgG. After lipid lowering, VCAM-1
      and MCP-1 expression decreased, eNOS expression increased, and ECs exhibited a
      more normal ultrastructure. CONCLUSIONS: These results establish that lipid
      lowering can reduce oxidative stress and EC activation in vivo. These mechanisms
      may contribute to improvement in endothelial function and plaque stabilization
      observed clinically.

PMID- 12221059
TI  - Detection of experimental autoimmune myocarditis in rats by 111In monoclonal
      antibody specific for tenascin-C.
AB  - BACKGROUND: Although the identification of inflammatory infiltrates in
      endomyocardial biopsy specimens is necessary for the definite diagnosis of
      myocarditis, the biopsy test is invasive and is not sensitive. Therefore, a new
      diagnostic technique for the early and noninvasive evaluation of myocarditis has
      been awaited. Expression of tenascin-C (TNC), one of the oligometric
      extracellular glycoproteins, is induced in various pathological states, including
      inflammation, suggesting that TNC can be a molecular marker of myocarditis.
      METHODS AND RESULTS: An 111In anti-TNC monoclonal antibody Fab' fragment was
      injected intravenously into rats with experimental autoimmune myocarditis (EAM),
      and the biodistribution of this radiotracer was measured. Rapid clearance of
      radioactivity from the blood was observed in both EAM and control rats (<1% at 6
      hours after injection). Myocardial uptake of the tracer was much higher in EAM
      rats than in control rats (7.54-, 4.39-, and 3.51-fold at 6, 24, and 48 hours
      after injection, respectively). By autoradiography, high radioactivities were
      clearly observed in the regions indicative of inflammation in EAM rats. Single
      photon emission CT imaging demonstrated the focal myocardial uptake of 111In anti
      TNC Fab' in vivo. CONCLUSIONS: Radiolabeled anti-TNC Fab' may be useful for the
      noninvasive diagnosis of myocarditis.

PMID- 12221060
TI  - Overexpression of thioredoxin-1 in transgenic mice attenuates adriamycin-induced
      cardiotoxicity.
AB  - BACKGROUND: Adriamycin (ADR) is an anticancer drug known to cause severe cardiac
      toxicity by generating free radicals. We investigated the role of a redox
      regulating molecule, thioredoxin-1 (TRX1), in ADR-induced cardiotoxicity. METHODS
      AND RESULTS: The in vitro study showed that TRX1 was dose-dependently increased
      concomitant with the formation of hydroxyl radicals in ADR-treated neonatal rat
      cardiomyocytes. Lactate dehydrogenase-releasing assay showed that treatment with
      recombinant human TRX1 suppressed cardiomyocyte injury in ADR-treated
      cardiomyocytes. To examine the biological significance of TRX1 in vivo, we used
      transgenic mice expressing increased levels of human TRX1 (TRX1-TG mice).
      Electron microscopy revealed that mitochondria, myofibrils, and other cellular
      details were much better maintained in ADR-treated TRX1-TG mice than in ADR
      treated nontransgenic (WT) mice. The increase in the protein carbonyl content, a
      marker of cellular protein oxidation, was suppressed in ADR-treated TRX1-TG mice
      compared with ADR-treated WT mice. The formation of hydroxyl radicals in ADR
      treated heart homogenates of TRX1-TG mice was decreased compared with WT mice.
      For the survival study, all WT mice treated with ADR died within 6 weeks, but 5
      of 6 TRX1-TG mice treated with ADR survived >8 weeks. CONCLUSIONS: TRX1 is
      upregulated by intracellular oxidative stress generated by ADR. TRX1 has a
      protective role against ADR-induced cardiotoxicity by reducing oxidative stress.

PMID- 12221061
TI  - Kb-R7943 prevents acute, atrial fibrillation-induced shortening of atrial
      refractoriness in anesthetized dogs.
AB  - BACKGROUND: To test the hypothesis that Ca2+ influx via Na+/Ca2+ exchange (NCX)
      underlies atrial fibrillation (AF)-induced shortening of atrial effective
      refractory period (AERP), we examined the potential of KB-R7943 (KB), a selective
      inhibitor of Ca2+-influx mode NCX, to attenuate this effect. METHODS AND RESULTS:
      Studies were performed in 41 isoflurane-anesthetized dogs. In sinus rhythm dogs,
      peak AERP changes resulting from intravenous KB infusion ranged from (mean+/-SEM)
      4.4+/-0.4% (1 mg/kg) to 14.8+/-2.6% (5 mg/kg; ED50=1.9 mg/kg). AERP was maximally
      prolonged between 5 and 10 minutes after beginning of KB infusion and returned to
      baseline values within 30 minutes thereafter. Rapid atrial pacing-induced AF
      reversibly shortened AERP (P<0.001) in 5 dogs, averaging 14.9+/-2.1% after 90
      minutes of AF. Both the time course and magnitude of mean AERP changes in 5 AF
      dogs receiving 5 mg/kg KB were indistinguishable from those in 5 sinus rhythm
      dogs receiving an equivalent KB dose (P>0.05). We measured cardiac tissue and
      arterial plasma KB concentrations produced by intravenous infusion (1 mg x kg(-1)
      x min(-1)) of 5 mg/kg KB. Plasma drug concentration peaked at the end of KB
      infusions (30.86+/-3.26 nmol/L; n=4 dogs) and declined to 0.56+/-0.19 nmol/L
      after 100 minutes. The cardiac tissue-to-plasma drug concentration gradient
      averaged approximately 40 at 100 minutes after start of KB infusion. KB at
      concentrations achieved in vivo irreversibly blocked NCX-mediated Ca2+ influx in
      isolated canine right atrial myocytes by approximately 60%, but had no
      significant effect on NCX-dependent Ca2+ extrusion. CONCLUSION: NCX-mediated Ca2+
      influx plays an important role in acute, AF-induced AERP shortening.

PMID- 12221062
TI  - Cardiovascular manifestations of HIV infection.

PMID- 12221063
TI  - Images in cardiovascular medicine. Paroxysmal fibrillation within an isolated
      pulmonary vein.

PMID- 12221064
TI  - Images in cardiovascular medicine. Fate of intracardiac lead vegetations after
      percutaneous lead extraction.

PMID- 12221065
TI  - Biphasic effects of statins on angiogenesis.

PMID- 12221066
TI  - Assessing coronary endothelial dysfunction.

PMID- 12221067
TI  - Heat shock proteins and endotoxin combined as a trigger for inflammatory cytokine
      release during cardiopulmonary bypass: a possible third way?

PMID- 12221068
TI  - News from the 2002 Congress of the European Society of Cardiology: the Hotlines.

PMID- 12221069
TI  - Adenovirus triggers macropinocytosis and endosomal leakage together with its
      clathrin-mediated uptake.
AB  - Adenovirus type 2 (Ad2) binds the coxsackie B virus Ad receptor and is
      endocytosed upon activation of the alphav integrin coreceptors. Here, we
      demonstrate that expression of dominant negative clathrin hub, eps15, or K44A
      dynamin (dyn) inhibited Ad2 uptake into epithelial cells, indicating clathrin
      dependent viral endocytosis. Surprisingly, Ad strongly stimulated the endocytic
      uptake of fluid phase tracers, coincident with virus internalization but without
      affecting receptor-mediated transferrin uptake. A large amount of the stimulated
      endocytic activity was macropinocytosis. Macropinocytosis depended on alphav
      integrins, PKC, F-actin, and the amiloride-sensitive Na+/H+ exchanger, which are
      all required for Ad escape from endosomes and infection. Macropinocytosis
      stimulation was not a consequence of viral escape, since it occurred in K44A-dyn
      expressing cells. Surprisingly, 30-50% of the endosomal contents were released
      into the cytosol of control and also K44A-dyn-expressing cells, and the number of
      fluid phase-positive endosomes dropped below the levels of noninfected cells,
      indicating macropinosomal lysis. The release of macropinosomal contents was Ad
      dose dependent, but the presence of Ad particles on macropinosomal membranes was
      not sufficient for contents release. We conclude that Ad signaling from the cell
      surface controls the induction of macropinosome formation and leakage, and this
      correlates with viral exit to the cytosol and infection.

PMID- 12221070
TI  - Agrin plays an organizing role in the formation of sympathetic synapses.
AB  - Agrin is a nerve-derived factor that directs neuromuscular synapse formation,
      however its role in regulating interneuronal synaptogenesis is less clear. Here,
      we examine agrin's role in synapse formation between cholinergic preganglionic
      axons and sympathetic neurons in the superior cervical ganglion (SCG) using agrin
      deficient mice. In dissociated cultures of SCG neurons, we found a significant
      decrease in the number of synapses with aggregates of presynaptic synaptophysin
      and postsynaptic neuronal acetylcholine receptor among agrin-deficient neurons as
      compared to wild-type neurons. Moreover, the levels of pre- and postsynaptic
      markers at the residual synapses in agrin-deficient SCG cultures were also
      reduced, and these defects were rescued by adding recombinant neural agrin to the
      cultures. Similarly, we observed a decreased matching of pre- and postsynaptic
      markers in SCG of agrin-deficient embryos, reflecting a decrease in the number of
      differentiated synapses in vivo. Finally, in electrophysiological experiments, we
      found that paired-pulse depression was more pronounced and posttetanic
      potentiation was significantly greater in agrin-deficient ganglia, indicating
      that synaptic transmission is also defective. Together, these findings indicate
      that neural agrin plays an organizing role in the formation and/or
      differentiation of interneuronal, cholinergic synapses.

PMID- 12221071
TI  - Alpha1-syntrophin-deficient skeletal muscle exhibits hypertrophy and aberrant
      formation of neuromuscular junctions during regeneration.
AB  - Alpha1-syntrophin is a member of the family of dystrophin-associated proteins; it
      has been shown to recruit neuronal nitric oxide synthase and the water channel
      aquaporin-4 to the sarcolemma by its PSD-95/SAP-90, Discs-large, ZO-1 homologous
      domain. To examine the role of alpha1-syntrophin in muscle regeneration, we
      injected cardiotoxin into the tibialis anterior muscles of alpha1-syntrophin-null
      (alpha1syn-/-) mice. After the treatment, alpha1syn-/- muscles displayed
      remarkable hypertrophy and extensive fiber splitting compared with wild-type
      regenerating muscles, although the untreated muscles of the mutant mice showed no
      gross histological change. In the hypertrophied muscles of the mutant mice, the
      level of insulin-like growth factor-1 transcripts was highly elevated.
      Interestingly, in an early stage of the regeneration process, alpha1syn-/- mice
      showed remarkably deranged neuromuscular junctions (NMJs), accompanied by
      impaired ability to exercise. The contractile forces were reduced in alpha1syn-/-
      regenerating muscles. Our results suggest that the lack of alpha1-syntrophin
      might be responsible in part for the muscle hypertrophy, abnormal synapse
      formation at NMJs, and reduced force generation during regeneration of dystrophin
      deficient muscle, all of which are typically observed in the early stages of
      Duchenne muscular dystrophy patients.

PMID- 12221072
TI  - The role of the Tim8p-Tim13p complex in a conserved import pathway for
      mitochondrial polytopic inner membrane proteins.
AB  - Tim23p is imported via the TIM (translocase of inner membrane)22 pathway for
      mitochondrial inner membrane proteins. In contrast to precursors with an NH2
      terminal targeting presequence that are imported in a linear NH2-terminal manner,
      we show that Tim23p crosses the outer membrane as a loop before inserting into
      the inner membrane. The Tim8p-Tim13p complex facilitates translocation across the
      intermembrane space by binding to the membrane spanning domains as shown by
      Tim23p peptide scans with the purified Tim8p-Tim13p complex and crosslinking
      studies with Tim23p fusion constructs. The interaction between Tim23p and the
      Tim8p-Tim13p complex is not dependent on zinc, and the purified Tim8p-Tim13p
      complex does not coordinate zinc in the conserved twin CX3C motif. Instead, the
      cysteine residues seemingly form intramolecular disulfide linkages. Given that
      proteins of the mitochondrial carrier family also pass through the TOM
      (translocase of outer membrane) complex as a loop, our study suggests that this
      translocation mechanism may be conserved. Thus, polytopic inner membrane
      proteins, which lack an NH2-terminal targeting sequence, pass through the TOM
      complex as a loop followed by binding of the small Tim proteins to the
      hydrophobic membrane spanning domains.

PMID- 12221073
TI  - Age-related changes in human bone proteoglycan structure. Impact of osteogenesis
      imperfecta.
AB  - Proteoglycans (PGs) are a family of molecules that undergo extensive post
      translational modifications that include addition of glycosaminoglycan (GAG)
      chains as well as N- and O-linked oligosaccharides to the protein core. PG
      composition and structure have been reported to alter with age. To test whether
      the post-translational modifications to PGs can serve as in vitro surrogate end
      point markers for chronological age, the extent of GAG modifications was
      determined for PGs derived from normal human bone cells of 14 donors (age range,
      fetal to 60 years). Isolated cells were steady state radiolabeled with
      (35)SO(4)(2-) and [(3)H]GlcN. For biglycan and decorin, iduronate content was
      linearly correlated with age (increased 1.5x between fetal and age 60 years). For
      the syndecan-like heparan sulfate PG, the N-sulfation of post-natal cells
      increased over 3.5-fold until reaching a plateau during the 4th decade of life.
      The amount of O-linked oligosaccharides was also found to decrease as a function
      of increasing normal donor age, whereas the specific activity of the metabolic
      precursor pool remained constant regardless of donor age. These age-related
      changes in post-translational modifications were then used to demonstrate that
      osteoblasts derived from patients with osteogenesis imperfecta did not exhibit
      facets of a pre-mature aging, but rather were arrested in a fetal-like phenotypic
      state. A growth matrix rich in thrombospondin altered PG metabolism in
      osteoblastic cells, resulting in the production and secretion of the fetal-like
      (rich in O-linked oligosaccharides) forms of decorin and biglycan. This effect
      was qualitatively different from the effect of transforming growth factor-beta,
      which predominantly altered GAGs rather than O-linked oligosaccharides. No other
      Arg-Gly-Asp protein (fibronectin, vitronectin, type I collagen, osteopontin, and
      bone sialoprotein) showed any detectable effect on PG metabolism in bone cells.
      These results indicate that a proper matrix stoichiometry is critical for
      metabolism of PGs.

PMID- 12221074
TI  - Trypanosoma cruzi H+-ATPase 1 (TcHA1) and 2 (TcHA2) genes complement yeast
      mutants defective in H+ pumps and encode plasma membrane P-type H+-ATPases with
      different enzymatic properties.
AB  - Previous studies in Trypanosoma cruzi have shown that intracellular pH
      homeostasis requires ATP and is affected by H(+)-ATPase inhibitors, indicating a
      major role for ATP-driven proton pumps in intracellular pH control. In the
      present study, we report the cloning and sequencing of a pair of genes linked in
      tandem (TcHA1 and TcHA2) in T. cruzi which encode proteins with homology to
      fungal and plant P-type proton-pumping ATPases. The genes are expressed at the
      mRNA level in different developmental stages of T. cruzi: TcHA1 is expressed
      maximally in epimastigotes, whereas TcHA2 is expressed predominantly in
      trypomastigotes. The proteins predicted from the nucleotide sequence of the genes
      have 875 and 917 amino acids and molecular masses of 96.3 and 101.2 kDa,
      respectively. Full-length TcHA1 and an N-terminal truncated version of TcHA2
      complemented a Saccharomyces cerevisiae strain deficient in P-type H(+)-ATPase
      activity, the proteins localized to the yeast plasma membrane, and ATP-driven
      proton pumping could be detected in proteoliposomes reconstituted from plasma
      membrane purified from transfected yeast. The reconstituted proton transport
      activity was reduced by inhibitors of P-type H(+)-ATPases. C-terminal truncation
      did not affect complementation of mutant yeast, suggesting the lack of C-terminal
      autoinhibitory domains in these proteins. ATPase activity in plasma membrane from
      TcHA1- and (N-terminal truncated) TcHA2-transfected yeast was inhibited to
      different extents by vanadate, whereas the latter yeast strain was more resistant
      to extremes of pH, suggesting that the native proteins may serve different
      functions at different stages in the T. cruzi life cycle.

PMID- 12221075
TI  - Glutathione peroxidase-1 protects from CD95-induced apoptosis.
AB  - Through the induction of apoptosis, CD95 plays a crucial role in the immune
      response and the elimination of cancer cells. Ligation of CD95 receptor activates
      a complex signaling network that appears to implicate the generation of reactive
      oxygen species (ROS). This study investigated the place of ROS production in CD95
      mediated apoptosis and the role of the antioxidant enzyme glutathione peroxidase
      1 (GPx1). Anti-CD95 antibodies triggered an early generation of ROS in human
      breast cancer T47D cells that was blocked by overexpression of GPx1 and
      inhibition of initiator caspase activation. Enforced expression of GPx1 also
      resulted in inhibition of CD95-induced effector caspase activation, DNA
      fragmentation, and apoptotic cell death. Resistance to CD95-mediated apoptosis
      was not due to an increased expression of anti-apoptotic molecules and could be
      reversed by glutathione-depleting agents. In addition, whereas the anti-apoptotic
      protein Bcl-xL prevented CD95-induced apoptosis in MCF-7 cells, it did not
      inhibit the early ROS production. Moreover, Bcl-xL but not GPx1 overexpression
      could suppress the staurosporine-induced late generation of ROS and subsequent
      cell death. Altogether, these findings suggest that GPx1 functions upstream of
      the mitochondrial events to inhibit the early ROS production and apoptosis
      induced by CD95 ligation. Finally, transgenic mice overexpressing GPx1 were
      partially protected from the lethal effect of anti-CD95, underlying the
      importance of peroxide formation (and GPx1) in CD95-triggered apoptosis.

PMID- 12221076
TI  - Nocodazole-induced p53-dependent c-Jun N-terminal kinase activation reduces
      apoptosis in human colon carcinoma HCT116 cells.
AB  - Microtubule-interfering agents are widely used in cancer chemotherapy, and
      prognostic results vary significantly from tumor to tumor, depending on the p53
      status. In preliminary experiments, we compared the expression and
      phosphorylation profiles of more than 100 protein kinases and protein
      phosphatases in human colorectal carcinoma cell line HCT116 between p53+/+ and
      p53-/- cells in response to short term nocodazole treatment through application
      of Kinetworks immunoblotting screens. Among the proteins tracked, the regulation
      of the phosphorylation of c-Jun N-terminal kinase (JNK)1/2 at Thr-183/Tyr-185 was
      the major difference between p53+/+ and p53-/- cells. With the loss of the p53
      gene, the levels of phosphorylation of Ser-63 of c-Jun and Thr-183/Tyr-185 of
      JNK1/2 in p53-/- cells did not increase as markedly as in p53+/+ cells in
      response to a 1-h treatment with nocodazole or other microtubule-disrupting drugs
      such as vinblastine and colchicine. Similar observations were also made in MCF-7
      and A549 tumor cells, which were rendered p53-deficient by E6 oncoprotein
      expression. However, arsenate-induced JNK activation in p53-/- cells was
      preserved. Inhibition of p53 expression by its antisense oligonucleotide also
      attenuated nocodazole-induced JNK activation in p53+/+ cells. Surprisingly,
      cotransfection of p53+/+ cells with dominant negative mutants of JNK isoforms and
      treatment of p53+/+ cells with the JNK inhibitor SP600125 actually further
      enhanced apoptosis in p53+/+ cells by up to 2-fold in response to nocodazole.
      These findings indicate that inhibition of p53-mediated JNK1/2 activity in
      certain tumor cells could serve to enhance the apoptosis-inducing actions of
      cancer chemotherapeutic agents that disrupt mitotic spindle function.

PMID- 12221077
TI  - The RhoA-binding protein, rhophilin-2, regulates actin cytoskeleton organization.
AB  - The Rho GTPases regulate the actin cytoskeleton through interactions with various
      downstream effector molecules. Here we have identified a ubiquitously expressed
      human RhoA-binding protein, designated Rhophilin-2. Rhophilin-2 shows 40% amino
      acid similarity to human Rhophilin-1 and contains an N-terminal Rho-binding, a
      central Bro1-like, and a C-terminal PDZ domain. Glutathione S-transferase-capture
      experiments revealed that Rhophilin-1 and Rhophilin-2 interacted with both GDP-
      and GTP-bound RhoA in vitro. Despite the ability of Rhophilin-1 and Rhophilin-2
      to interact with RhoA in a nucleotide-independent fashion, Rho-induced serum
      response element transcriptional activity was not altered by expression of either
      of these molecules. Although Rhophilin-2-expressing HeLa cells showed a loss of
      actin stress fibers, Rhophilin-1 expression had no noticeable effect on the actin
      cytoskeleton. Coexpression of Rhophilin-2 with a constitutively active Rho mutant
      reversed the disassembly phenotype, in which the coexpressing cells were more
      spread and less contracted than Rho alone-expressing cells. Expression of various
      Rhophilin-2 deletion and point mutants containing the N-terminal RhoA-binding
      domain but lacking other regions suggested that the disassembly of F-actin stress
      fibers was not simply caused by Rho sequestration. In addition, the Bro1 and PDZ
      domains of Rhophilin-2 were required for disassembly. RhoA activity assays also
      revealed that Rhophilin-2-expressing cells showed increased levels of RhoA-GTP
      suggesting that the Rhophilin-2-induced disassembly of stress fibers was not
      mediated by decreased RhoA activity. Based on the biochemical and biological
      activity, Rhophilin-2 may function normally in a Rho pathway to limit stress
      fiber formation and/or increase the turnover of F-actin structures in the absence
      of high levels of RhoA activity.

PMID- 12221078
TI  - Distinct signaling pathways are activated in response to mechanical stress
      applied axially and transversely to skeletal muscle fibers.
AB  - In the diaphragm muscle we tested the hypothesis that MAP kinase signaling
      pathways are activated by mechanical stress and such signaling pathways are
      dependent on the direction in which mechanical stress is applied. Although equal
      magnitudes of mechanical stress were applied axially and transversely a greater
      level of activation of ERK1/2, p38, Raf-1, p90 RSK, Elk-1, and the DNA binding
      activity of AP-1 transcription factor was produced when the muscle was stretched
      transversely than when stretched axially. A significant up-regulation in protein
      tyrosine phosphorylation was observed in axially or transversely loaded diaphragm
      muscles and the activation of ERK1/2 was completely inhibited by genistein
      (protein-tyrosine kinase inhibitor). Pretreatment of muscles with wortmannin
      (phosphoinositide 3-kinase inhibitor), TMB-8 (antagonist of intracellular calcium
      release), GF109203X (PKC inhibitor), or PD98059 (MEK1/2 inhibitor) blocked the
      activation of ERK1/2 kinases in response to axial but not to transverse loading.
      On the other hand, pretreatment of muscles with protein kinase A inhibitors H-7
      and KT5720 completely suppressed the activation of ERK1/2 in response to
      transverse loading only. Taken together with the alterations of MAP kinases and
      the findings of elevations of downstream transcription targets, our data are
      consistent with two distinct MAP kinase signal transduction pathways in response
      to mechanical stress.

PMID- 12221079
TI  - Protein kinase C (PKC)-induced phosphorylation of ROMK1 is essential for the
      surface expression of ROMK1 channels.
AB  - We carried out in vitro phosphorylation assays to determine whether ROMK1 is a
      substrate of protein kinase C (PKC) and used the two-electrode voltage clamp
      method to investigate the role of serine residues 4, 183, and 201, the three
      putative PKC phosphorylation sites, in the regulation of ROMK1 channel activity.
      Incubation of the purified His-tagged ROMK1 protein with PKC and radiolabeled ATP
      resulted in (32)P incorporation into ROMK1 detected by autoradiography. Moreover,
      the in vitro phosphorylation study of three synthesized peptides corresponding to
      amino acids 1-16, 174-189, and 196-211 of ROMK1 revealed that serine residues 4
      and 201 of ROMK1 were the two main PKC phosphorylation sites. In contrast, (32)P
      incorporation of peptide 174-189 was absent. In vitro phosphorylation studies
      with ROMK1 mutants, R1S4/201A, R1S4/183A, and R1S183/201A, demonstrated that the
      phosphorylation levels of R1S4/201A were significantly lower than those of the
      other two mutants. Also, the Ba(2+)-sensitive K(+) current in oocytes injected
      with green fluorescent protein (GFP)-R1S4/201A was only 5% of that in oocytes
      injected with wild type GFP-ROMK1. In contrast, the K(+) current in oocytes
      injected with GFP-ROMK1 mutants containing either serine residue 4 or 201 was
      similar to those injected with wild type ROMK1. Confocal microscope imaging shows
      that the surface expression of the K(+) channels was significantly diminished in
      oocytes injected with R1S4/201A and completely absent in oocytes injected with
      R1S4/183/201A. Furthermore, the biotin labeling technique confirmed that the
      membrane fraction of ROMK channels was almost absent in HEK293 cells transfected
      with either R1S4/201A or R1S4/183/201A. However, when serine residues 4 and 201
      were mutated to aspartate, the K(+) currents and the surface expression were
      completely restored. Finally, addition of calphostin C in the incubation medium
      significantly decreased the K(+) current in comparison with that under control
      conditions. Biotin labeling technique further indicated that inhibition of PKC
      decreases the surface ROMK1 expression in human embryonic kidney (HEK) cells
      transfected with ROMK1. We conclude that ROMK1 is a substrate of PKC and that
      serine residues 4 and 201 are the two main PKC phosphorylation sites that are
      essential for the expression of ROMK1 in the cell surface.

PMID- 12221080
TI  - Slac2-c (synaptotagmin-like protein homologue lacking C2 domains-c), a novel
      linker protein that interacts with Rab27, myosin Va/VIIa, and actin.
AB  - Slac2-a (synaptotagmin-like protein (Slp) homologue lacking C2 domains
      a)/melanophilin is a melanosome-associated protein that links Rab27A on
      melanosomes with myosin Va, an actin-based motor protein, and formation of the
      tripartite protein complex (Rab27A.Slac2-a.myosin Va) has been suggested to
      regulate melanosome transport (Fukuda, M., Kuroda, T. S., and Mikoshiba, K.
      (2002) J. Biol. Chem. 277, 12432-12436). Here we report the structure of a novel
      form of Slac2, named Slac2-c, that is homologous to Slac2-a. Slac2-a and Slac2-c
      exhibit the same overall structure, consisting of a highly conserved N-terminal
      Slp homology domain (about 50% identity) and a less conserved C-terminal myosin
      Va-binding domain (about 20% identity). As with other Slac2 members and the Slp
      family, the Slp homology domain of Slac2-c was found to interact specifically
      with the GTP-bound form of Rab27A/B both in vitro and in intact cells, and the C
      terminal domain of Slac2-c interacted with myosin Va and myosin VIIa. In
      addition, we discovered that the most C-terminal conserved region of Slac2-a
      (amino acids 400-590) and Slac2-c (amino acids 670-856), which is not essential
      for myosin Va binding, directly binds actin and that expression of these regions
      in PC12 cells and melanoma cells colocalized with actin filaments at the cell
      periphery, suggesting a novel role of Slac2-a/c in capture of Rab27-containing
      organelles in the actin-enriched cell periphery.

PMID- 12221081
TI  - Crystal structure of microbial transglutaminase from Streptoverticillium
      mobaraense.
AB  - The crystal structure of a microbial transglutaminase from Streptoverticillium
      mobaraense has been determined at 2.4 A resolution. The protein folds into a
      plate-like shape, and has one deep cleft at the edge of the molecule. Its overall
      structure is completely different from that of the factor XIII-like
      transglutaminase, which possesses a cysteine protease-like catalytic triad. The
      catalytic residue, Cys(64), exists at the bottom of the cleft. Asp(255) resides
      at the position nearest to Cys(64) and is also adjacent to His(274).
      Interestingly, Cys(64), Asp(255), and His(274) superimpose well on the catalytic
      triad "Cys-His-Asp" of the factor XIII-like transglutaminase, in this order. The
      secondary structure frameworks around these residues are also similar to each
      other. These results imply that both transglutaminases are related by convergent
      evolution; however, the microbial transglutaminase has developed a novel
      catalytic mechanism specialized for the cross-linking reaction. The structure
      accounts well for the catalytic mechanism, in which Asp(255) is considered to be
      enzymatically essential, as well as for the causes of the higher reaction rate,
      the broader substrate specificity, and the lower deamidation activity of this
      enzyme.

PMID- 12221082
TI  - Galpha and Gbeta gamma require distinct Src-dependent pathways to activate Rap1
      and Ras.
AB  - The Src tyrosine kinase is necessary for activation of extracellular signal
      regulated kinases (ERKs) by the beta-adrenergic receptor agonist, isoproterenol.
      In this study, we examined the role of Src in the stimulation of two small G
      proteins, Ras and Rap1, that have been implicated in isoproterenol's signaling to
      ERKs. We demonstrate that the activation of isoproterenol of both Rap1 and Ras
      requires Src. In HEK293 cells, isoproterenol activates Rap1, stimulates Rap1
      association with B-Raf, and activates ERKs, all via PKA. In contrast, the
      activation by isoproterenol of Ras requires Gbetagamma subunits, is independent
      of PKA, and results in the phosphoinositol 3-kinase-dependent activation of AKT.
      Interestingly, beta-adrenergic stimulation of both Rap1 and ERKs, but not Ras and
      AKT, can be blocked by a Src mutant (SrcS17A) that is incapable of being
      phosphorylated and activated by PKA. Furthermore, a Src mutant (SrcS17D), which
      mimics PKA phosphorylation at serine 17, stimulates Rap1 activation, Rap1/B-Raf
      association, and ERK activation but does not stimulate Ras or AKT. These data
      suggest that Rap1 activation, but not that of Ras, is mediated through the direct
      phosphorylation of Src by PKA. We propose that the beta(2)-adrenergic receptor
      activates Src via two independent mechanisms to mediate distinct signaling
      pathways, one through Galpha(s) to Rap1 and ERKs and the other through Gbetagamma
      to Ras and AKT.

PMID- 12221083
TI  - Homologues of human macrophage migration inhibitory factor from a parasitic
      nematode. Gene cloning, protein activity, and crystal structure.
AB  - Cytokines are the molecular messengers of the vertebrate immune system,
      coordinating the local and systemic immune responses to infective organisms. We
      report here functional and structural data on cytokine-like proteins from a
      eukaryotic pathogen. Two homologues of the human cytokine macrophage migration
      inhibitory factor (MIF) have been isolated from the parasitic nematode Brugia
      malayi. Both molecules (Bm-MIF-1 and Bm-MIF-2) show parallel functions to human
      MIF. They are chemotactic for human monocytes and activate them to produce IL-8,
      TNF-alpha, and endogenous MIF. The human and nematode MIF homologues share a
      tautomerase enzyme activity, which is in each case abolished by the mutation of
      the N-terminal proline residue. The crystal structure of Bm-MIF-2 at 1.8-A
      resolution has been determined, revealing a trimeric assembly with an inner pore
      created by beta-stranded sheets from each subunit. Both biological activity and
      crystal structure reveal remarkable conservation between a human cytokine and its
      parasite counterpart despite the considerable phylogenetic divide among these
      organisms. The strength of the similarity implies that MIF-mediated pathways play
      an important role in nematode immune evasion strategies.

PMID- 12221084
TI  - NHE1 regulates the stratum corneum permeability barrier homeostasis.
      Microenvironment acidification assessed with fluorescence lifetime imaging.
AB  - The outermost epidermal layer, the stratum corneum (SC), exhibits an acidic
      surface pH, whereas the pH at its base approaches neutrality. NHE1 is the only
      Na(+)/H(+) antiporter isoform in keratinocytes and epidermis, and has been shown
      to regulate intracellular pH. We now demonstrate a novel function for NHE1, as we
      find that it also controls acidification of extracellular "microdomains" in the
      SC that are essential for activation of pH-sensitive enzymes and the formation of
      the epidermal permeability barrier. NHE1 expression in epidermis is most
      pronounced in granular cell layers, and although the surface pH of NHE1 knockout
      mice is only slightly more alkaline than normal using conventional pH
      measurements, a more sensitive method, fluorescence lifetime imaging,
      demonstrates that the acidic intercellular domains at the surface and of the
      lower SC disappear in NHE1 -/- animals. Fluorescence lifetime imaging studies
      also reveal that SC acidification does not occur through a uniform gradient, but
      through the progressive accumulation of acidic microdomains. These findings not
      only visualize the spatial distribution of the SC pH gradient, but also
      demonstrate a role for NHE1 in the generation of acidic extracellular domains of
      the lower SC, thus providing the acidification of deep SC interstices necessary
      for lipid processing and barrier homeostasis.

PMID- 12221086
TI  - Removal of Pex3p is an important initial stage in selective peroxisome
      degradation in Hansenula polymorpha.
AB  - Selective degradation of peroxisomes (macropexophagy) in Hansenula polymorpha
      involves the sequestration of individual organelles to be degraded by membranes
      prior to the fusion of this compartment with the vacuole and subsequent
      degradation of the whole organelle by vacuolar hydrolases. Here we show that
      Pex3p, a peroxisomal membrane protein essential for peroxisome biogenesis,
      escapes this autophagic process. Upon induction of macropexophagy, Pex3p is
      removed from the organelle tagged for degradation prior to its sequestration. Our
      data indicate that Pex3p degradation is essential to allow the initiation of the
      organellar degradation process. Also, in a specific peroxisome degradation
      deficient (pdd) mutant in which sequestration still occurs but the vacuolar
      fusion event is disturbed, the turnover of Pex3p is still observed. Taken
      together, our data suggest that degradation of Pex3p is part of the initial
      degradation machinery of individual peroxisomes.

PMID- 12221087
TI  - Retinoblastoma tumor suppressor targets dNTP metabolism to regulate DNA
      replication.
AB  - The retinoblastoma tumor suppressor, RB, is a negative regulator of the cell
      cycle that is inactivated in the majority of human tumors. Cell cycle inhibition
      elicited by RB has been attributed to the attenuation of CDK2 activity. Although
      ectopic cyclins partially overcome RB-mediated S-phase arrest at the replication
      fork, DNA replication remains inhibited and cells fail to progress to G(2) phase.
      These data suggest that RB regulates an additional execution point in S phase. We
      observed that constitutively active RB attenuates the expression of specific dNTP
      synthetic enzymes: dihydrofolate reductase, ribonucleotide reductase (RNR)
      subunits R1/R2, and thymidylate synthase (TS). Activation of endogenous RB and
      related proteins by p16ink4a yielded similar effects on enzyme expression.
      Conversely, targeted disruption of RB resulted in increased metabolic protein
      levels (dihydrofolate reductase, TS, RNR-R2) and conferred resistance to the
      effect of TS or RNR inhibitors that diminish available dNTPs. Analysis of dNTP
      pools during RB-mediated cell cycle arrest revealed significant depletion,
      concurrent with the loss of TS and RNR protein. Importantly, the effect of active
      RB on cell cycle position and available dNTPs was comparable to that observed
      with specific antimetabolites. Together, these results show that RB-mediated
      transcriptional repression attenuates available dNTP pools to control S-phase
      progression. Thus, RB employs both canonical cyclin-dependent kinase/cyclin
      regulation and metabolic regulation as a means to limit proliferation,
      underscoring its potency in tumor suppression.

PMID- 12221088
TI  - Evidence for plasticity and structural mimicry at the immunoglobulin light chain
      protein L interface.
AB  - The multidomain bacterial surface protein L (PpL) is a virulence factor expressed
      by only 10% of Peptostreptococcus magnus strains, and its expression is
      correlated with bacterial vaginosis. The molecular basis for its ability to
      recognize 60% of mammalian immunoglobulin light chain variable regions (V(L)) has
      been described recently by x-ray crystallography, which suggested the presence of
      two V(L) binding sites on each protein L domain (Graille, M., Stura, E. A.,
      Housden, N. G., Beckingham, J. A., Bottomley, S. P., Beale, D., Taussig, M. J.,
      Sutton, B. J., Gore, M. G., and Charbonnier, J. (2001) Structure 9, 679-687).
      Here, we report the crystal structure at 2.1 A resolution of a protein L mutant
      complexed to an Fab' fragment with only 50% of the V(L) residues interacting with
      PpL site 1 conserved. Comparison of the site 1 interface from both structures
      shows how protein L is able to accommodate these sequence differences and
      therefore bind to a large repertoire of Ig. The x-ray structure and NMR results
      confirm the existence of two V(L) binding sites on a single protein L domain.
      These sites exhibit a remarkable structural mimicry of growth factors binding to
      their receptors. This could explain the protein L superantigenic activity on
      human B lymphocytes.

PMID- 12221089
TI  - Dynamics-modulated biological activity of transforming growth factor beta3.
AB  - Transforming growth factor beta3 (TGF-beta3) is an important mediator of growth,
      maintenance, and repair processes in human cells. Internal dynamic properties
      have been derived from (15)N NMR relaxation data and mapped onto the spatial
      structure of TGF-beta3. The pattern of internal dynamics in the structure
      identifies potential "hot spots" of binding free energy and reveals the
      importance of conformational entropy in the interaction of TGF-beta3 with the
      receptors. The observed internal dynamics set TGF-beta3 apart from other TGF-beta
      isoforms, with which it shares the same fold. These findings may explain
      functional differences among the various TGF-beta isoforms and thus prove
      essential in the search for related therapeutic agents.

PMID- 12221085
TI  - IKKalpha, IKKbeta, and NEMO/IKKgamma are each required for the NF-kappa B
      mediated inflammatory response program.
AB  - The IKKbeta and NEMO/IKKgamma subunits of the NF-kappaB-activating signalsome
      complex are known to be essential for activating NF-kappaB by inflammatory and
      other stress-like stimuli. However, the IKKalpha subunit is believed to be
      dispensable for the latter responses and instead functions as an in vivo mediator
      of other novel NF-kappaB-dependent and -independent functions. In contrast to
      this generally accepted view of IKKalpha's physiological functions, we
      demonstrate in mouse embryonic fibroblasts (MEFs) that, akin to IKKbeta and
      NEMO/IKKgamma, IKKalpha is also a global regulator of tumor necrosis factor alpha
      and IL-1-responsive IKK signalsome-dependent target genes including many known
      NF-kappaB targets such as serum amyloid A3, C3, interleukin (IL)-6, IL-11, IL-1
      receptor antagonist, vascular endothelial growth factor, Ptx3, beta(2)
      microglobulin, IL-1alpha, Mcp-1 and -3, RANTES (regulated on activation normal T
      cell expressed and secreted), Fas antigen, Jun-B, c-Fos, macrophage colony
      stimulating factor, and granulocyte-macrophage colony-stimulating factor. Only a
      small number of NF-kappaB-dependent target genes were preferentially dependent on
      IKKalpha or IKKbeta. Constitutive expression of a trans-dominant IkappaBalpha
      superrepressor (IkappaBalphaSR) in wild type MEFs confirmed that these signalsome
      dependent target genes were also dependent on NF-kappaB. A subset of NF-kappaB
      target genes were IKK-dependent in the absence of exogenous stimuli, suggesting
      that the signalsome was also required to regulate basal levels of activated NF
      kappaB in established MEFs. Overall, a sizable number of novel NF-kappaB/IKK
      dependent genes were identified including Secreted Frizzled, cadherin 13,
      protocadherin 7, CCAAT/enhancer-binding protein-beta and -delta, osteoprotegerin,
      FOXC2 and FOXF2, BMP-2, p75 neurotrophin receptor, caspase-11, guanylate-binding
      proteins 1 and 2, ApoJ/clusterin, interferon (alpha and beta) receptor 2,
      decorin, osteoglycin, epiregulin, proliferins 2 and 3, stromal cell-derived
      factor, and cathepsins B, F, and Z. SOCS-3, a negative effector of STAT3
      signaling, was found to be an NF-kappaB/IKK-induced gene, suggesting that IKK
      mediated NF-kappaB activation can coordinately illicit negative effects on STAT
      signaling.

PMID- 12221090
TI  - Structural analysis of the autoinhibition of Ets-1 and its role in protein
      partnerships.
AB  - The DNA-binding activity of the eukaryotic transcription factor Ets-1 (E26 avian
      erythroblastosis virus oncogene-E twenty-six) is negatively regulated by
      inhibitory regions that flank the ETS domain. Based on the results of solution
      studies, these N- and C-terminal inhibitory regions have been proposed to pack
      against the ETS domain and form an autoinhibitory module whose N terminus
      partially unfolds upon binding of Ets-1 to DNA. Mutations that disrupt
      autoinhibition of DNA binding also cause a structural change in the inhibitory
      region. We report here a crystallographic study of fragments of Ets-1 that
      provide structural details of the inhibitory module and the structural transition
      that accompanies DNA binding. The structures of free and DNA-bound Ets-1
      fragments containing the ETS domain and the inhibitory regions confirm that the N
      terminal inhibitory region contains two alpha-helices one of which unfolds upon
      Ets-1 binding to DNA. The observations from the crystal structure, coupled with
      mutagenesis experiments, allow us to propose a model for the inhibited form of
      Ets-1 and lend insight into the flexible interaction between Ets-1 and the acute
      myeloid leukemia 1 protein, AML1 (RUNX1).

PMID- 12221091
TI  - Dynamics of myo1c (myosin-ibeta ) lipid binding and dissociation.
AB  - Myosin-I is the single-headed member of the myosin superfamily that associates
      with lipid membranes. Biochemical experiments have shown that myosin-I membrane
      binding is the result of electrostatic interactions between the basic tail domain
      and acidic phospholipids. To better understand the dynamics of myosin-I membrane
      association, we measured the rates of association and dissociation of a
      recombinant myo1c tail domain (which includes three IQ domains and bound
      calmodulins) to and from large unilamellar vesicles using fluorescence resonance
      energy transfer. The apparent second-order rate constant for lipid-tail
      association in the absence of calcium is fast with nearly every lipid-tail
      collision resulting in binding. The rate of binding is decreased in the presence
      of calcium. Time courses of myo1c-tail dissociation are best fit by two
      exponential rates: a fast component that has a rate that depends on the ratio of
      acidic phospholipid to myo1c-tail (phosphatidylserine (PS)/tail) and a slow
      component that predominates at high PS/tail ratios. The dissociation rate of the
      slow component is slower than the myo1c ATPase rate, suggesting that myo1c is
      able to stay associated with the lipid membrane during multiple catalytic cycles
      of the motor. Calcium significantly increases the lifetimes of the membrane-bound
      state, resulting in dissociation rates 0.001 s(-1).

PMID- 12221092
TI  - Distribution of PG-M/versican variants in human tissues and de novo expression of
      isoform V3 upon endothelial cell activation, migration, and neoangiogenesis in
      vitro.
AB  - We have carried out a comprehensive molecular mapping of PG-M/versican isoforms
      V0-V3 in adult human tissues and have specifically investigated how the
      expression of these isoforms is regulated in endothelial cells in vitro. A survey
      of 21 representative tissues highlighted a prevalence of V1 mRNA; demonstrated
      that the relative frequency of expression was V1 > V2 > V3 >or= V2; and showed
      that <15% of the tissues transcribed significant levels of all four isoforms. By
      employing novel and previously described anti-versican antibodies we verified a
      ubiquitous versican deposition in normal and tumor-associated vascular structures
      and disclosed differences in the glycanation profiles of versicans produced in
      different vascular beds. Resting endothelial cells isolated from different tissue
      sources transcribed several of the versican isoforms but consistently failed to
      translate these mRNAs into detectable proteoglycans. However, if stimulated with
      tumor necrosis factor-alpha or vascular endothelial growth factor, they altered
      their versican expression by de novo transcribing the V3 isoform and by
      exhibiting a moderate V1/V2 production. Induced versican synthesis and de novo V3
      expression was also observed in endothelial cells elicited to migrate in a wound
      healing model in vitro and in angiogenic endothelial cells forming tubule-like
      structures in Matrigel or fibrin clots. The results suggest that, independent of
      the degree of vascularization, human adult tissues show a limited expression of
      versican isoforms V0, V2, and V3 and that endothelial cells may contribute to the
      deposition of versican in vascular structures, but only following proper
      stimulation.

PMID- 12221093
TI  - High level of uncoupling protein 1 expression in muscle of transgenic mice
      selectively affects muscles at rest and decreases their IIb fiber content.
AB  - The mitochondrial uncoupling protein of brown adipose tissue (UCP1) was expressed
      in skeletal muscle and heart of transgenic mice at levels comparable with the
      amount found in brown adipose tissue mitochondria. These transgenic mice have a
      lower body weight, and when related to body weight, food intake and energy
      expenditure are increased. A specific reduction of muscle mass was observed but
      varied according to the contractile activity of muscles. Heart and soleus muscle
      are unaffected, indicating that muscles undergoing regular contractions, and
      therefore with a continuous mitochondrial ATP production, are protected. In
      contrast, the gastrocnemius and plantaris muscles showed a severely reduced mass
      and a fast to slow shift in fiber types promoting mainly IIa and IIx fibers at
      the expense of fastest and glycolytic type IIb fibers. These observations are
      interpreted as a consequence of the strong potential dependence of the UCP1
      protonophoric activity, which ensures a negligible proton leak at the membrane
      potential observed when mitochondrial ATP production is intense. Therefore UCP1
      is not deleterious for an intense mitochondrial ATP production and this explains
      the tolerance of the heart to a high expression level of UCP1. In muscles at
      rest, where ATP production is low, the rise in membrane potential enhances UCP1
      activity. The proton return through UCP1 mimics the effect of a sustained ATP
      production, permanently lowering mitochondrial membrane potential. This very
      likely constitutes the origin of the signal leading to the transition in fiber
      types at rest.

PMID- 12221094
TI  - Molecular determinants of syntaxin 1 modulation of N-type calcium channels.
AB  - We have previously reported that syntaxin 1A, a component of the presynaptic
      SNARE complex, directly modulates N-type calcium channel gating in addition to
      promoting tonic G-protein inhibition of the channels, whereas syntaxin 1B affects
      channel gating but does not support G-protein modulation (Jarvis, S. E., and
      Zamponi, G. W. (2001) J. Neurosci. 21, 2939-2948). Here, we have investigated the
      molecular determinants that govern the action of syntaxin 1 isoforms on N-type
      calcium channel function. In vitro evidence shows that both syntaxin 1 isoforms
      physically interact with the G-protein beta subunit and the synaptic protein
      interaction (synprint) site contained within the N-type calcium channel domain II
      III linker region. Moreover, in vitro evidence suggests that distinct domains of
      syntaxin participate in each interaction, with the COOH-terminal SNARE domain
      (residues 183-230) binding to Gbeta and the N-terminal (residues 1-69) binding to
      the synprint motif of the channel. Electrophysiological analysis of chimeric
      syntaxin 1A/1B constructs reveals that the variable NH(2)-terminal domains of
      syntaxin 1 are responsible for the differential effects of syntaxin 1A and 1B on
      N-type calcium channel function. Because syntaxin 1 exists in both "open" and
      "closed" conformations during exocytosis, we produced a constitutively open form
      of syntaxin 1A and found that it still promoted G-protein inhibition of the
      channels, but it did not affect N-type channel availability. This state
      dependence of the ability of syntaxin 1 to mediate N-type calcium channel
      availability suggests that syntaxin 1 dynamically regulates N-type channel
      function during various steps of exocytosis. Finally, syntaxin 1A appeared to
      compete with Ggamma for the Gbeta subunit both in vitro and under physiological
      conditions, suggesting that syntaxin 1A may contain a G-protein gamma subunit
      like domain.

PMID- 12221095
TI  - Specific molecular interactions of oversulfated chondroitin sulfate E with
      various heparin-binding growth factors. Implications as a physiological binding
      partner in the brain and other tissues.
AB  - We previously observed that the cortical neuronal cell adhesion mediated by
      midkine (MK), a heparin (Hep)-binding growth factor, is specifically inhibited by
      oversulfated chondroitin sulfate-E (CS-E) (Ueoka, C., Kaneda, N., Okazaki, I.,
      Nadanaka, S., Muramatsu, T., and Sugahara, K. (2000) J. Biol. Chem. 275, 37407
      37413) and that CS-E exhibits neurite outgrowth promoting activities toward
      embryonic rat hippocampal neurons. We have also shown oversulfated CS chains in
      embryonic chick and rat brains and demonstrated that the CS disaccharide
      composition changes during brain development. In view of these findings, here we
      tested the possibility of CS-E interacting with Hep-binding growth factors during
      development, using squid cartilage CS-E. The binding ability of Hep-binding
      growth factors (MK, pleiotrophin (PTN), fibroblast growth factor-1 (FGF-1), FGF
      2, Hep-binding epidermal growth factor-like growth factor (HB-EGF), FGF-10, FGF
      16, and FGF-18) toward [(3)H]CS-E was first tested by a filter binding assay,
      which demonstrated direct binding of all growth factors, except FGF-1, to CS-E.
      The bindings were characterized further in an Interaction Analysis system, where
      all of the growth factors, except FGF-1, gave concentration-dependent and
      specific bindings. The kinetic constants k(a), k(d), and K(d) suggested that MK,
      PTN, FGF-16, FGF-18, and HB-EGF bound strongly to CS-E, in comparable degrees to
      the binding to Hep, whereas the intensity of binding of FGF-2 and FGF-10 toward
      CS-E was lower than that for Hep. These findings suggest the possibility of CS-E
      being a binding partner, a coreceptor, or a genuine receptor for various Hep
      binding growth factors in the brain and possibly also in other tissues.

PMID- 12221096
TI  - XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC.
AB  - Rho proteins cycle between an inactive, GDP-bound state and an active, GTP-bound
      state. Activation of these GTPases is mediated by guanine nucleotide exchange
      factors (GEFs), which promote GDP to GTP exchange. In this study we have
      characterized XPLN, a Rho family GEF. Like other Rho GEFs, XPLN contains a tandem
      Dbl homology and pleckstrin homology domain topography, but lacks homology with
      other known functional domains or motifs. XPLN protein is expressed in the brain,
      skeletal muscle, heart, kidney, platelets, and macrophage and neuronal cell
      lines. In vitro, XPLN stimulates guanine nucleotide exchange on RhoA and RhoB,
      but not RhoC, RhoG, Rac1, or Cdc42. Consistent with these data, XPLN
      preferentially associates with RhoA and RhoB. The specificity of XPLN for RhoA
      and RhoB, but not RhoC, is surprising given that they share over 85% sequence
      identity. We determined that the inability of XPLN to exchange RhoC is mediated
      by isoleucine 43 in RhoC, a position occupied by valine in RhoA and RhoB. When
      expressed in cells, XPLN activates RhoA and RhoB, but not RhoC, and stimulates
      the assembly of stress fibers and focal adhesions in a Rho kinase-dependent
      manner. We also found that XPLN possesses transforming activity, as determined by
      focus formation assays. In conclusion, here we describe a Rho family GEF that can
      discriminate between the closely related RhoA, RhoB, and RhoC, possibly giving
      insight to the divergent functions of these three proteins.

PMID- 12221097
TI  - Inhibition of caspases protects cerebellar granule cells of the weaver mouse from
      apoptosis and improves behavioral phenotype.
AB  - The homozygous mouse mutant weaver exhibits a massive loss of cerebellar granule
      neurons postnatally. The death of these cells is associated with a single amino
      acid mutation in the G protein-activated inwardly rectifying potassium channel,
      Girk2. Evidence suggests that both the mutated Girk2 channel and the calcium
      channel-associated N-methyl-d-aspartate receptor play important roles in the
      apoptotic death of weaver cerebellar granule cells, but the downstream events
      associated with this process are unknown. In this study, we demonstrate that the
      consequences of the mutation result in caspase activation. In addition, our
      results show that caspase inhibition in vivo decreases caspase activation and
      granule cell apoptosis and significantly improves behavioral deficits associated
      with the weaver's phenotype.

PMID- 12221098
TI  - Increased hepatic Forkhead Box M1B (FoxM1B) levels in old-aged mice stimulated
      liver regeneration through diminished p27Kip1 protein levels and increased Cdc25B
      expression.
AB  - Recent liver regeneration studies indicate that maintaining hepatic Forkhead Box
      M1B (FoxM1B) expression in 12-month-old (old-aged) Transthyretin-FoxM1B
      transgenic mice increases hepatocyte proliferation and expression of cell cycle
      regulatory genes. Because these transgenic CD-1 mice maintain FoxM1B levels
      during the aging process, we conducted the current study to determine whether
      adenovirus delivery of the FoxM1B gene (AdFoxM1B) is sufficient to stimulate
      liver regeneration in old-aged Balb/c mice. Here we show that AdFoxM1B infection
      of old-aged mice caused a significant increase in FoxM1B expression, hepatocyte
      DNA replication, and mitosis following partial hepatectomy. This stimulation in
      hepatocyte S-phase progression was associated with diminished protein expression
      and perinuclear localization of cyclin-dependent kinase (Cdk) inhibitor p27(Kip1)
      (p27) protein following partial hepatectomy. In contrast, old-aged mice infected
      with control virus displayed high hepatocyte levels of p27 protein, which had
      been localized to the nucleus prior to S-phase. Furthermore, we found that
      restoring FoxM1B expression did not influence p27 mRNA levels, and this new
      finding implicates FoxM1B in regulation of p27 protein levels. Likewise, AdFoxM1B
      infected regenerating livers displayed elevated S-phase levels of Cdk2 kinase
      activity compared with old-aged mice infected with control virus. Furthermore,
      restoring FoxM1B expression in old-aged mice caused elevated levels of Cyclin B1,
      Cyclin B2, Cdc25B, Cdk1, and p55CDC mRNA as well as stimulating Cdc25B nuclear
      localization during liver regeneration, all of which are required for mitosis.
      These studies indicated that an acute delivery of the FoxM1B gene in old-aged
      mice is sufficient to re-establish proliferation of regenerating hepatocytes,
      suggesting that FoxM1B can be used for therapeutic intervention to alleviate the
      reduction in cellular proliferation observed in the elderly.

PMID- 12221099
TI  - ERK5 MAPK regulates embryonic angiogenesis and acts as a hypoxia-sensitive
      repressor of vascular endothelial growth factor expression.
AB  - During angiogenesis, endothelial cells undergo proliferation, reorganization, and
      stabilization to establish a mature vascular network. This process is critical
      for establishing a functional circulatory system during development and
      contributes to the pathological process of tumor growth. Here we report that
      embryos deficient for the ERK5 MAPK die between embryonic days 10.5 and 11.5 with
      angiogenic failure and cardiovascular defects. We show that ERK5 deficiency leads
      to an increased expression of the vascular endothelial growth factor (VEGF),
      dysregulation of which has been shown to impede angiogenic remodeling and
      vascular stabilization. Our data also reveal that ERK5 negatively regulates
      transcription from the vegf locus during hypoxic responses. Importantly, ERK5 is
      required at an earlier developmental stage than p38alpha, and p38alpha does not
      compensate for ERK5 deficiency. These results demonstrate that ERK5 plays a
      specific role in the regulation of early angiogenesis.

PMID- 12221100
TI  - The surface of lipid droplets is a phospholipid monolayer with a unique Fatty
      Acid composition.
AB  - We found that caveolin-2 is targeted to the surface of lipid droplets (Fujimoto,
      T., Kogo, H., Ishiguro, K., Tauchi, K., and Nomura, R. (2001) J. Cell Biol. 152,
      1079-1085) and hypothesized that the lipid droplet surface is a kind of membrane.
      To elucidate the characteristics of the lipid droplet surface, we isolated lipid
      droplets from HepG2 cells and analyzed them by cryoelectron microscopy and by
      mass spectrometry. By use of cryoelectron microscopy at the stage temperature of
      4.2 K, the lipid droplet surface was observed as a single line without any
      fixation or staining, indicating the presence of a single layer of phospholipids.
      This result appeared consistent with the hypothesis that the lipid droplet
      surface is derived from the cytoplasmic leaflet of the endoplasmic reticulum
      membrane and may be continuous to it. However, mass spectrometry revealed that
      the fatty acid composition of phosphatidylcholine and lysophosphatidylcholine in
      lipid droplets is different from that of the rough endoplasmic reticulum. The
      ample presence of free cholesterol in lipid droplets also suggests that their
      surface is differentiated from the bulk endoplasmic reticulum membrane. On the
      other hand, although caveolin-2beta and adipose differentiation-related protein,
      both localizing in lipid droplets, were enriched in the low density floating
      fraction, the fatty acid composition of the fraction was distinct from lipid
      droplets. Collectively, the result indicates that the lipid droplet surface is a
      hemi-membrane or a phospholipid monolayer containing cholesterol but is
      compositionally different from the endoplasmic reticulum membrane or the
      sphingolipid/cholesterol-rich microdomain.

PMID- 12221102
TI  - Acyl-intermediate structures of the extended-spectrum class A beta-lactamase,
      Toho-1, in complex with cefotaxime, cephalothin, and benzylpenicillin.
AB  - Bacterial resistance to beta-lactam antibiotics is a serious problem limiting
      current clinical therapy. The most common form of resistance is the production of
      beta-lactamases that inactivate beta-lactam antibiotics. Toho-1 is an extended
      spectrum beta-lactamase that has acquired efficient activity not only to
      penicillins but also to cephalosporins including the expanded-spectrum
      cephalosporins that were developed to be stable in former beta-lactamases. We
      present the acyl-intermediate structures of Toho-1 in complex with cefotaxime
      (expanded-spectrum cephalosporin), cephalothin (non-expanded-spectrum
      cephalosporin), and benzylpenicillin at 1.8-, 2.0-, and 2.1-A resolutions,
      respectively. These structures reveal distinct features that can explain the
      ability of Toho-1 to hydrolyze expanded-spectrum cephalosporins. First, the Omega
      loop of Toho-1 is displaced to avoid the steric contacts with the bulky side
      chain of cefotaxime. Second, the conserved residues Asn(104) and Asp(240) form
      unique interactions with the bulky side chain of cefotaxime to fix it tightly.
      Finally, the unique interaction between the conserved Ser(237) and cephalosporins
      probably helps to bring the beta-lactam carbonyl group to the suitable position
      in the oxyanion hole, thus increasing the cephalosporinase activity.

PMID- 12221101
TI  - Clostridium perfringens iota toxin. Mapping of the Ia domain involved in docking
      with Ib and cellular internalization.
AB  - Clostridium perfringens iota toxin consists of two unlinked proteins. The binding
      component (Ib) is required to internalize into cells an enzymatic component (Ia)
      that ADP-ribosylates G-actin. To characterize the Ia domain that interacts with
      Ib, fusion proteins were constructed between the C. botulinum C3 enzyme, which
      ADP-ribosylates Rho, and various truncated versions of Ia. These chimeric
      molecules retained the wild type ADP-ribosyltransferase activity specific for Rho
      and were recognized by antibodies against C3 enzyme and Ia. Internalization of
      each chimera into Vero cells was assessed by measuring the disorganization of the
      actin cytoskeleton and intracellular ADP-ribosylation of Rho. Fusion proteins
      containing C3 linked to the C terminus of Ia were transported most efficiently
      into cells like wild type Ia in an Ib-dependent manner that was blocked by
      bafilomycin A1. The minimal Ia fragment that promoted translocation of Ia-C3
      chimeras into cells consisted of 128 central residues (129-257). These findings
      revealed that iota toxin is a suitable system for mediating the entry of
      heterologous proteins such as C3 into cells.

PMID- 12221103
TI  - Inhibitor-2 regulates protein phosphatase-1 complexed with NimA-related kinase to
      induce centrosome separation.
AB  - Centrosome separation is regulated by balance of in situ protein
      kinase/phosphatase activities during the cell cycle. The mammalian NimA-related
      kinase Nek2 forms a complex with the catalytic subunit of protein phosphatase-1
      (PP1C). This complex is located at centrosomes and has been implicated in
      regulation of the cycle of duplication and separation. Inhibitor-2 (Inh2) is an
      inhibitor protein specific for PP1C, and its expression level fluctuates during
      the cell cycle. Here we report cellular regulation of the Nek2.PP1C complex by
      Inh2. PP1C-binding segments of Nek2 were isolated by yeast two-hybrid screening
      using Inh2 bait. Inh2 indirectly associates with Nek2 via PP1C, which binds to
      both proteins, forming a bridged heterotrimeric complex. Double Ala mutation of
      the PP1C-binding site (KVHF) in Nek2 eliminated both PP1C and Inh2 interactions
      in both a yeast conjugation assay and an in vitro binding assay. The kinase
      activity of Nek2.PP1C was enhanced 2-fold by addition of recombinant Inh2, with
      EC(50) = 10 nm. Immunofluorescence showed concentration of endogenous Inh2 at
      centrosomes and in a region surrounding the centrosomes. Transient expression of
      wild-type Inh2 increased by 5-fold dispersed/split centrosomes in fibroblasts,
      mimicking the phenotype produced by overexpression of Nek2. Deletion of the Inh2
      C-terminal domain yielded Inh2-(1-118), which failed to interact with or activate
      the Nek2.PP1C complex, suggesting that the C-terminal region of Inh2 is required
      for regulation of the Nek2.PP1C complex. Thus, Inh2 can enhance the kinase
      activity of the Nek2.PP1C complex via inhibition of phosphatase activity to
      initiate centrosome separation.

PMID- 12221104
TI  - Detailed kinetic analysis and identification of the nucleophile in alpha-L
      arabinofuranosidase from Geobacillus stearothermophilus T-6, a family 51
      glycoside hydrolase.
AB  - alpha-l-Arabinofuranosidases cleave the l-arabinofuranoside side chains of
      different hemicelluloses and are key enzymes in the complete degradation of the
      plant cell wall. The alpha-l-arabinofuranosidase from Geobacillus
      stearothermophilus T-6, a family 51 glycoside hydrolase, was subjected to a
      detailed mechanistic study. Aryl-alpha-l-arabinofuranosides with various leaving
      groups were synthesized and used to verify the catalytic mechanism and catalytic
      residues of the enzyme. The steady-state constants and the resulting Bronsted
      plots for the E175A mutant are consistent with the role of Glu-175 as the acid
      base catalytic residue. The proposed nucleophile residue, Glu-294, was replaced
      to Ala by a double-base pairs substitution. The resulting E294A mutant, with 4
      nitrophenyl alpha-l-arabinofuranoside as the substrate, exhibited eight orders of
      magnitude lower activity and a 10-fold higher K(m) value compared with the wild
      type enzyme. Sodium azide accelerated by more than 40-fold the rate of the
      hydrolysis of 2',4',6'-trichlorophenyl alpha-l-arabinofuranoside by the E294A
      mutant. The glycosyl-azide product formed during this reaction was isolated and
      characterized as beta-l-arabinofuranosyl-azide by (1)H NMR, (13)C NMR, mass
      spectrometry, and Fourier transform infrared analysis. The anomeric configuration
      of this product supports the assignment of Glu-294 as the catalytic nucleophile
      residue of the alpha-l-arabinofuranosidase T-6 and allows for the first time the
      unequivocal identification of this residue in glycoside hydrolases family 51.

PMID- 12221105
TI  - Transcriptional activators differ in their abilities to control alternative
      splicing.
AB  - Promoter and enhancer elements can influence alternative splicing, but the basis
      for this phenomenon is not well understood. Here we investigated how different
      transcriptional activators affect the decision between inclusion and exclusion
      (skipping) of the fibronectin EDI exon. A mutant of the acidic VP16 activation
      domain called SW6 that preferentially inhibits polymerase II (pol II) elongation
      caused a reduction in EDI exon skipping. Exon skipping was fully restored in the
      presence of the SW6 mutant by either the SV40 enhancer in cis or the human
      immunodeficiency virus (HIV) Tat in trans, both of which specifically stimulate
      pol II elongation. HIV Tat also cooperated with the Sp1 and CTF activation
      domains to enhance transcript elongation and EDI skipping. The extent of exon
      skipping correlated with the efficiency with which pol II transcripts reach the
      3' end of the gene but not with the overall fold increase in transcript levels
      caused by different activators. The ability of activators to enhance elongation
      by RNA polymerase II therefore correlates with their ability to enhance exon
      skipping. Consistent with this observation, the elongation inhibitor
      dichlororibofuranosylbenzimidazole (DRB) enhanced EDI inclusion. Conversely, the
      histone deacetylase inhibitor trichostatin A that is thought to stimulate
      elongation caused a modest inhibition of EDI inclusion. Together our results
      support a kinetic coupling model in which the rate of transcript elongation
      determines the outcome of two competing splicing reactions that occur co
      transcriptionally. Rapid, highly processive transcription favors EDI exon
      skipping, whereas slower, less processive transcription favors inclusion.

PMID- 12221106
TI  - Crystal structure of the cytoskeleton-associated protein glycine-rich (CAP-Gly)
      domain.
AB  - Cytoskeleton-associated proteins (CAPs) are involved in the organization of
      microtubules and transportation of vesicles and organelles along the cytoskeletal
      network. A conserved motif, CAP-Gly, has been identified in a number of CAPs,
      including CLIP-170 and dynactins. The crystal structure of the CAP-Gly domain of
      Caenorhabditis elegans F53F4.3 protein, solved by single wavelength sulfur
      anomalous phasing, revealed a novel protein fold containing three beta-sheets.
      The most conserved sequence, GKNDG, is located in two consecutive sharp turns on
      the surface, forming the entrance to a groove. Residues in the groove are highly
      conserved as measured from the information content of the aligned sequences. The
      C-terminal tail of another molecule in the crystal is bound in this groove.

PMID- 12221107
TI  - ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin,
      and AP-2.
AB  - Mutations in the phosphotyrosine binding domain protein ARH cause autosomal
      recessive hypercholesterolemia, a disorder caused by defective internalization of
      low density lipoprotein receptors (LDLR) in the liver. To examine the function of
      ARH, we used pull-down experiments to test for interactions between ARH, the
      LDLR, and proteins involved in clathrin-mediated endocytosis. The phosphotyrosine
      binding domain of ARH interacted with the internalization sequence (NPVY) in the
      cytoplasmic tail of LDLR in a sequence-specific manner. Mutations in the NPVY
      sequence that were previously shown to decrease LDLR internalization abolished in
      vitro binding to ARH. Recombinant ARH bound purified bovine clathrin with high
      affinity (K(D), approximately 44 nm). The interaction between ARH and clathrin
      was mapped to a canonical clathrin box sequence (LLDLE) in ARH and to the N
      terminal domain of the clathrin heavy chain. A highly conserved 20-amino acid
      sequence in the C-terminal region of ARH bound the beta(2)-adaptin subunit of AP
      2. Mutation of a glutamic acid residue in the appendage domain of beta(2)-adaptin
      that is required for interaction with the adapter protein beta-arrestin markedly
      reduced binding to ARH. These data are consistent with the hypothesis that ARH
      functions as an adaptor protein that couples LDLR to the endocytic machinery.

PMID- 12221108
TI  - Negative regulation of interleukin-12 signaling by suppressor of cytokine
      signaling-1.
AB  - Suppressor of cytokine signaling-1 (SOCS-1) is an inhibitory protein that
      regulates responses to cytokines. Previously, we have shown SOCS-1 to be a key
      inhibitor of interferon gamma (IFNgamma). Recent data suggest that SOCS-1 may
      regulate other cytokines in vivo, in addition to IFNgamma. Uncontrolled responses
      to interleukin-12 (IL-12), an inflammatory cytokine, could contribute to
      increased IFNgamma production and the development of inflammatory disease in SOCS
      1(-/-) mice. Here, we assess responses of SOCS-1-deficient cells to IL-12. Both
      IL-12-induced T cell proliferation and NK cytotoxic activity are enhanced in SOCS
      1-deficient cells, relative to controls. To examine the contribution of continued
      IL-12 signaling to the SOCS-1(-/-) disease, we generated mice lacking both SOCS-1
      and signal transducer and activator of transcription 4 (STAT4), an essential
      component of the IL-12 signaling pathway. SOCS-1(-/-) STAT4(-/-) mice have
      improved survival relative to SOCS-1(-/-) mice, but die between 1 and 2 months of
      age. We conclude that, in addition to IFNgamma, SOCS-1 regulates responses to IL
      12.

PMID- 12221109
TI  - A conditional mutation affecting localization of the Menkes disease copper
      ATPase. Suppression by copper supplementation.
AB  - Copper is an essential co-factor for several key metabolic processes. This
      requirement in humans is underscored by Menkes disease, an X-linked copper
      deficiency disorder caused by mutations in the copper transporting P-type ATPase,
      MNK. MNK is located in the trans-Golgi network where it transports copper to
      secreted cuproenzymes. Increases in copper concentration stimulate the
      trafficking of MNK to the plasma membrane where it effluxes copper. In this
      study, a Menkes disease mutation, G1019D, located in the large cytoplasmic loop
      of MNK, was characterized in transfected cultured cells. In copper-limiting
      conditions the G1019D mutant protein was retained in the endoplasmic reticulum.
      However, this mislocalization was corrected by the addition of copper to cells
      via a process that was dependent upon the copper binding sites at the N-terminal
      region of MNK. Reduced growth temperature and the chemical chaperone, glycerol,
      were found to correct the mislocalization of the G1019D mutant, suggesting this
      mutation interferes with protein folding in the secretory pathway. These findings
      identify G1019D as the first conditional mutation associated with Menkes disease
      and demonstrate correction of the mislocalized protein by copper supplementation.
      Our findings provide a molecular framework for understanding how mutations that
      affect the proper folding of the MNK transporter in Menkes patients may be
      responsive to parenteral copper therapy.

PMID- 12221110
TI  - Role of fission yeast Tup1-like repressors and Prr1 transcription factor in
      response to salt stress.
AB  - In Schizosaccharomyces pombe, the Sty1 mitogen-activated protein kinase and the
      Atf1 transcription factor control transcriptional induction in response to
      elevated salt concentrations. Herein, we demonstrate that two repressors, Tup11
      and Tup12, and the Prr1 transcription factor also function in the response to
      salt shock. We find that deletion of both tup genes together results in
      hypersensitivity to elevated cation concentrations (K(+) and Ca(2+)) and we
      identify cta3(+), which encodes an intracellular cation transporter, as a novel
      stress gene whose expression is positively controlled by the Sty1 pathway and
      negatively regulated by Tup repressors. The expression of cta3(+) is maintained
      at low levels by the Tup repressors, and relief from repression requires the
      Sty1, Atf1, and Prr1. Prr1 is also required for KCl-mediated induction of several
      other Sty1-dependent genes such as gpx1(+) and ctt1(+). Surprisingly, the KCl
      mediated induction of cta3(+) expression occurs independently of Sty1 in a
      tup11Delta tup12Delta mutant and so the Tup repressors link induction to the Sty1
      pathway. We also report that in contrast to a number of other Sty1- and Atf1
      dependent genes, the expression of cta3(+) is induced only by high salt
      concentrations. However, in the absence of the Tup repressors this specificity is
      lost and a range of stresses induces cta3(+) expression.

PMID- 12221111
TI  - The roles of bud-site-selection proteins during haploid invasive growth in yeast.
AB  - In haploid strains of Saccharomyces cerevisiae, glucose depletion causes invasive
      growth, a foraging response that requires a change in budding pattern from axial
      to unipolar-distal. To begin to address how glucose influences budding pattern in
      the haploid cell, we examined the roles of bud-site-selection proteins in
      invasive growth. We found that proteins required for bipolar budding in diploid
      cells were required for haploid invasive growth. In particular, the Bud8p
      protein, which marks and directs bud emergence to the distal pole of diploid
      cells, was localized to the distal pole of haploid cells. In response to glucose
      limitation, Bud8p was required for the localization of the incipient bud site
      marker Bud2p to the distal pole. Three of the four known proteins required for
      axial budding, Bud3p, Bud4p, and Axl2p, were expressed and localized
      appropriately in glucose-limiting conditions. However, a fourth axial budding
      determinant, Axl1p, was absent in filamentous cells, and its abundance was
      controlled by glucose availability and the protein kinase Snf1p. In the bud8
      mutant in glucose-limiting conditions, apical growth and bud site selection were
      uncoupled processes. Finally, we report that diploid cells starved for glucose
      also initiate the filamentous growth response.

PMID- 12221113
TI  - Distinct chromosome segregation roles for spindle checkpoint proteins.
AB  - The spindle checkpoint plays a central role in the fidelity of chromosome
      transmission by ensuring that anaphase is initiated only after kinetochore
      microtubule associations of all sister chromatid pairs are complete. In this
      study, we find that known spindle checkpoint proteins do not contribute equally
      to chromosome segregation fidelity in Saccharomyces cerevisiae. Loss of Bub1 or
      Bub3 protein elicits the largest effect. Analysis of Bub1p reveals the presence
      of two molecular functions. An N-terminal 608-amino acid (nonkinase) portion of
      the protein supports robust checkpoint activity, and, as expected, contributes to
      chromosome segregation. A C-terminal kinase-encoding segment independently
      contributes to chromosome segregation through an unknown mechanism. Both
      molecular functions depend on association with Bub3p. A 156-amino acid fragment
      of Bub1p functions in Bub3p binding and in kinetochore localization by one-hybrid
      assay. An adjacent segment is required for Mad1p binding, detected by deletion
      analysis and coimmunoprecipitation. Finally, overexpression of wild-type BUB1 or
      MAD3 genes leads to chromosome instability. Analysis of this activity indicates
      that the Bub3p-binding domain of Bub1p contributes to this phenotype through
      disruption of checkpoint activity as well as through introduction of kinetochore
      or spindle damage.

PMID- 12221112
TI  - Pkh1 and Pkh2 differentially phosphorylate and activate Ypk1 and Ykr2 and define
      protein kinase modules required for maintenance of cell wall integrity.
AB  - Saccharomyces cerevisiae Pkh1 and Pkh2 are functionally redundant homologs of
      mammalian protein kinase, phosphoinositide-dependent protein kinase-1. They
      activate two closely related, functionally redundant enzymes, Ypk1 and Ykr2
      (homologs of mammalian protein kinase, serum- and glucocorticoid-inducible
      protein kinase). We found that Ypk1 has a more prominent role than Ykr2 in
      mediating their shared essential function. Considerable evidence demonstrated
      that Pkh1 preferentially activates Ypk1, whereas Pkh2 preferentially activates
      Ykr2. Loss of Pkh1 (but not Pkh2) reduced Ypk1 activity; conversely, Pkh1
      overexpression increased Ypk1 activity more than Pkh2 overexpression. Loss of
      Pkh2 reduced Ykr2 activity; correspondingly, Pkh2 overexpression increased Ykr2
      activity more than Pkh1 overexpression. When overexpressed, a catalytically
      active C-terminal fragment (kinase domain) of Ypk1 was growth inhibitory; loss of
      Pkh1 (but not Pkh2) alleviated toxicity. Loss of Pkh2 (but not Pkh1) exacerbated
      the slow growth phenotype of a ypk1Delta strain. This Pkh1-Ypk1 and Pkh2-Ykr2
      dichotomy is not absolute because all double mutants (pkh1Delta ypk1Delta,
      pkh2Delta ypk1Delta, pkh1Delta ykr2Delta, and pkh2Delta ykr2Delta) were viable.
      Compartmentation contributes to selectivity because Pkh1 and Ypk1 were located
      exclusively in the cytosol, whereas Pkh2 and Ykr2 entered the nucleus. At
      restrictive temperature, ypk1-1(ts) ykr2Delta cells lysed rapidly, but not in
      medium containing osmotic support. Dosage and extragenic suppressors were
      selected. Overexpression of Exg1 (major exoglucanase), or loss of Kex2
      (endoprotease involved in Exg1 processing), rescued growth at high temperature.
      Viability was also maintained by PKC1 overexpression or an activated allele of
      the downstream protein kinase (BCK1-20). Conversely, absence of Mpk1 (distal
      mitogen-activated protein kinase of the PKC1 pathway) was lethal in ypk1-1(ts)
      ykr2Delta cells. Thus, Pkh1-Ypk1 and Pkh2-Ykr2 function in a novel pathway for
      cell wall integrity that acts in parallel with the Pkc1-dependent pathway.

PMID- 12221114
TI  - Activation of mitogen-activated protein kinase (mitogen-activated protein
      kinase/extracellular signal-regulated kinase) cascade by aldosterone.
AB  - Aldosterone in some tissues increases expression of the mRNA encoding the small
      monomeric G protein Ki-RasA. Renal A6 epithelial cells were used to determine
      whether induction of Ki-ras leads to concomitant increases in the total as well
      as active levels of Ki-RasA and whether this then leads to subsequent activation
      of its effector mitogen-activated protein kinase (MAPK/extracellular signal
      regulated kinase) cascade. The molecular basis and cellular consequences of this
      action were specifically investigated. We identified the intron 1-exon 1 region
      (rasI/E1) of the mouse Ki-ras gene as sufficient to reconstitute aldosterone
      responsiveness to a heterologous promotor. Aldosterone increased reporter gene
      activity containing rasI/E1 threefold. Aldosterone increased the absolute and GTP
      bound levels of Ki-RasA by a similar extent, suggesting that activation resulted
      from mass action and not effects on GTP binding/hydrolysis rates. Aldosterone
      significantly increased Ki-RasA and MAPK activity as early as 15 min with
      activation peaking by 2 h and waning after 4 h. Inhibitors of transcription,
      translation, and a glucocorticoid receptor antagonist attenuated MAPK signaling.
      Similarly, rasI/E1-driven luciferase expression was sensitive to glucocorticoid
      receptor blockade. Overexpression of dominant-negative RasN17, addition of
      antisense Ki-rasA and inhibition of mitogen-activated protein kinase kinase also
      attenuated steroid-dependent increases in MAPK signaling. Thus, activation of
      MAPK by aldosterone is dependent, in part, on a genomic mechanism involving
      induction of Ki-ras transcription and subsequent activation of its downstream
      effectors. This genomic mechanism has a distinct time course from activation by
      traditional mitogens, such as serum, which affect the GTP-binding state and not
      absolute levels of Ras. The result of such a genomic mechanism is that peak
      activation of the MAPK cascade by adrenal corticosteroids is delayed but
      prolonged.

PMID- 12221115
TI  - Functional heterogeneity of bone morphogenetic protein receptor-II mutants found
      in patients with primary pulmonary hypertension.
AB  - Germline mutations in the BMPR2 gene encoding bone morphogenetic protein (BMP)
      type II receptor (BMPR-II) have been reported in patients with primary pulmonary
      hypertension (PPH), but the contribution of various types of mutations found in
      PPH to the pathogenesis of clinical phenotypes has not been elucidated. To
      determine the biological activities of these mutants, we performed functional
      assays testing their abilities to transduce BMP signals. We found that the
      reported missense mutations within the extracellular and kinase domains of BMPR
      II abrogated their signal-transducing abilities. BMPR-II proteins containing
      mutations at the conserved cysteine residues in the extracellular and kinase
      domains were detected in the cytoplasm, suggesting that the loss of signaling
      ability of certain BMPR-II mutants is due at least in part to their altered
      subcellular localization. In contrast, BMPR-II mutants with truncation of the
      cytoplasmic tail retained the ability to transduce BMP signals. The differences
      in biological activities among the BMPR-II mutants observed thus suggest that
      additional genetic and/or environmental factors may play critical roles in the
      pathogenesis of PPH.

PMID- 12221116
TI  - Aurora B kinase exists in a complex with survivin and INCENP and its kinase
      activity is stimulated by survivin binding and phosphorylation.
AB  - Aurora B regulates chromosome segregation and cytokinesis and is the first
      protein to be implicated as a regulator of bipolar attachment of spindle
      microtubules to kinetochores. Evidence from several systems suggests that Aurora
      B is physically associated with inner centromere protein (INCENP) in mitosis and
      has genetic interactions with Survivin. It is unclear whether the Aurora B and
      INCENP interaction is cell cycle regulated and if Survivin physically interacts
      in this complex. In this study, we cloned the Xenopus Survivin gene, examined its
      association with Aurora B and INCENP, and determined the effect of its binding on
      Aurora B kinase activity. We demonstrate that in the Xenopus early embryo, all of
      the detectable Survivin is in a complex with both Aurora B and INCENP throughout
      the cell cycle. Survivin and Aurora B bind different domains on INCENP. Aurora B
      activity is stimulated >10-fold in mitotic extracts; this activation is
      phosphatase sensitive, and the binding of Survivin is required for full Aurora B
      activity. We also find the hydrodynamic properties of the Aurora
      B/Survivin/INCENP complex are cell cycle regulated. Our data indicate that Aurora
      B kinase activity is regulated by both Survivin binding and cell cycle-dependent
      phosphorylation.

PMID- 12221117
TI  - ADP-ribosylation factor (ARF) interaction is not sufficient for yeast GGA protein
      function or localization.
AB  - Golgi-localized gamma-ear homology domain, ADP-ribosylation factor (ARF)-binding
      proteins (GGAs) facilitate distinct steps of post-Golgi traffic. Human and yeast
      GGA proteins are only ~25% identical, but all GGA proteins have four similar
      domains based on function and sequence homology. GGA proteins are most conserved
      in the region that interacts with ARF proteins. To analyze the role of ARF in GGA
      protein localization and function, we performed mutational analyses of both human
      and yeast GGAs. To our surprise, yeast and human GGAs differ in their requirement
      for ARF interaction. We describe a point mutation in both yeast and mammalian GGA
      proteins that eliminates binding to ARFs. In mammalian cells, this mutation
      disrupts the localization of human GGA proteins. Yeast Gga function was studied
      using an assay for carboxypeptidase Y missorting and synthetic temperature
      sensitive lethality between GGAs and VPS27. Based on these assays, we conclude
      that non-Arf-binding yeast Gga mutants can function normally in membrane
      trafficking. Using green fluorescent protein-tagged Gga1p, we show that Arf
      interaction is not required for Gga localization to the Golgi. Truncation
      analysis of Gga1p and Gga2p suggests that the N-terminal VHS domain and C
      terminal hinge and ear domains play significant roles in yeast Gga protein
      localization and function. Together, our data suggest that yeast Gga proteins
      function to assemble a protein complex at the late Golgi to initiate proper
      sorting and transport of specific cargo. Whereas mammalian GGAs must interact
      with ARF to localize to and function at the Golgi, interaction between yeast Ggas
      and Arf plays a minor role in Gga localization and function.

PMID- 12221118
TI  - Inversin forms a complex with catenins and N-cadherin in polarized epithelial
      cells.
AB  - Nephrogenesis starts with the reciprocal induction of two embryonically distinct
      analages, metanephric mesenchyme and ureteric bud. This complex process requires
      the refined and coordinated expression of numerous developmental genes, such as
      inv. Mice that are homozygous for a mutation in the inv gene (inv/inv) develop
      renal cysts resembling autosomal-recessive polycystic kidney disease. The gene
      locus containing inv has been proposed to serve as a common modifier for some
      human and rodent polycystic kidney disease phenotypes. We generated polyclonal
      antibodies to inversin to study its subcellular distribution, potential binding
      partners, and functional aspects in cultured murine proximal tubule cells. A 125
      kDa inversin protein isoform was found at cell-cell junctions. Two inversin
      isoforms, 140- and 90-kDa, were identified in the nuclear and perinuclear
      compartments. Plasma membrane allocation of inversin is dependent upon cell-cell
      contacts and was redistributed when cell adhesion was disrupted after incubation
      of the cell monolayer with low-calcium/EGTA medium. We further show that the
      membrane-associated 125-kDa inversin forms a complex with N-cadherin and the
      catenins. The 90-kDa nuclear inversin complexes with beta-catenin. These findings
      indicate that the inv gene product functions in several cellular compartments,
      including the nucleus and cell-cell adhesion sites.

PMID- 12221119
TI  - Modulation of cellular cholesterol transport and homeostasis by Rab11.
AB  - To analyze the contribution of vesicular trafficking pathways in cellular
      cholesterol transport we examined the effects of selected endosomal Rab proteins
      on cholesterol distribution by filipin staining. Transient overexpression of
      Rab11 resulted in prominent accumulation of free cholesterol in Rab11-positive
      organelles that sequestered transferrin receptors and internalized transferrin.
      Sphingolipids were selectively redistributed as pyrene-sphingomyelin and
      sulfatide cosequestered with Rab11-positive endosomes, whereas globotriaosyl
      ceramide and GM2 ganglioside did not. Rab11 overexpression did not perturb the
      transport of 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine-perchlorate
      labeled low-density lipoprotein (LDL) to late endosomes or the Niemann-Pick type
      C1 (NPC1)-induced late endosomal cholesterol clearance in NPC patient cells.
      However, Rab11 overexpression inhibited cellular cholesterol esterification in an
      LDL-independent manner. This effect could be overcome by introducing cholesterol
      to the plasma membrane by using cyclodextrin as a carrier. These results suggest
      that in Rab11-overexpressing cells, deposition of cholesterol in recycling
      endosomes results in its impaired esterification, presumably due to defective
      recycling of cholesterol to the plasma membrane. The findings point to the
      importance of the recycling endosomes in regulating cholesterol and sphingolipid
      trafficking and cellular cholesterol homeostasis.

PMID- 12221120
TI  - All small nuclear RNAs (snRNAs) of the [U4/U6.U5] Tri-snRNP localize to nucleoli;
      Identification of the nucleolar localization element of U6 snRNA.
AB  - Previously, we showed that spliceosomal U6 small nuclear RNA (snRNA) transiently
      passes through the nucleolus. Herein, we report that all individual snRNAs of the
      [U4/U6.U5] tri-snRNP localize to nucleoli, demonstrated by fluorescence
      microscopy of nucleolar preparations after injection of fluorescein-labeled snRNA
      into Xenopus oocyte nuclei. Nucleolar localization of U6 is independent from
      [U4/U6] snRNP formation since sites of direct interaction of U6 snRNA with U4
      snRNA are not nucleolar localization elements. Among all regions in U6, the only
      one required for nucleolar localization is its 3' end, which associates with the
      La protein and subsequently during maturation of U6 is bound by Lsm proteins.
      This 3'-nucleolar localization element of U6 is both essential and sufficient for
      nucleolar localization and also required for localization to Cajal bodies.
      Conversion of the 3' hydroxyl of U6 snRNA to a 3' phosphate prevents association
      with the La protein but does not affect U6 localization to nucleoli or Cajal
      bodies.

PMID- 12221121
TI  - A role for Caenorhabditis elegans importin IMA-2 in germ line and embryonic
      mitosis.
AB  - The importin alpha family of nuclear-cytoplasmic transport factors mediates the
      nuclear localization of proteins containing classical nuclear localization
      signals. Metazoan animals express multiple importin alpha proteins, suggesting
      their possible roles in cell differentiation and development. Adult
      Caenorhabditis elegans hermaphrodites express three importin alpha proteins, IMA
      1, IMA-2, and IMA-3, each with a distinct expression and localization pattern.
      IMA-2 was expressed exclusively in germ line cells from the early embryonic
      through adult stages. The protein has a dynamic pattern of localization dependent
      on the stage of the cell cycle. In interphase germ cells and embryonic cells, IMA
      2 is cytoplasmic and nuclear envelope associated, whereas in developing oocytes,
      the protein is cytoplasmic and intranuclear. During mitosis in germ line cells
      and embryos, IMA-2 surrounded the condensed chromosomes but was not directly
      associated with the mitotic spindle. The timing of IMA-2 nuclear localization
      suggested that the protein surrounded the chromosomes after fenestration of the
      nuclear envelope in prometaphase. Depletion of IMA-2 by RNA-mediated gene
      interference (RNAi) resulted in embryonic lethality and a terminal aneuploid
      phenotype. ima-2(RNAi) embryos have severe defects in nuclear envelope formation,
      accumulating nucleoporins and lamin in the cytoplasm. We conclude that IMA-2 is
      required for proper chromosome dynamics in germ line and early embryonic mitosis
      and is involved in nuclear envelope assembly at the conclusion of mitosis.

PMID- 12221122
TI  - The major sites of cellular phospholipid synthesis and molecular determinants of
      Fatty Acid and lipid head group specificity.
AB  - Phosphatidylcholine and phosphatidylethanolamine are the two main phospholipids
      in eukaryotic cells comprising ~50 and 25% of phospholipid mass, respectively.
      Phosphatidylcholine is synthesized almost exclusively through the CDP-choline
      pathway in essentially all mammalian cells. Phosphatidylethanolamine is
      synthesized through either the CDP-ethanolamine pathway or by the decarboxylation
      of phosphatidylserine, with the contribution of each pathway being cell type
      dependent. Two human genes, CEPT1 and CPT1, code for the total compliment of
      activities that directly synthesize phosphatidylcholine and
      phosphatidylethanolamine through the CDP-alcohol pathways. CEPT1 transfers a
      phosphobase from either CDP-choline or CDP-ethanolamine to diacylglycerol to
      synthesize both phosphatidylcholine and phosphatidylethanolamine, whereas CPT1
      synthesizes phosphatidylcholine exclusively. We show through immunofluorescence
      that brefeldin A treatment relocalizes CPT1, but not CEPT1, implying CPT1 is
      found in the Golgi. A combination of coimmunofluorescence and subcellular
      fractionation experiments with various endoplasmic reticulum, Golgi, and nuclear
      markers confirmed that CPT1 was found in the Golgi and CEPT1 was found in both
      the endoplasmic reticulum and nuclear membranes. The rate-limiting step for
      phosphatidylcholine synthesis is catalyzed by the amphitropic CTP:phosphocholine
      cytidylyltransferase alpha, which is found in the nucleus in most cell types.
      CTP:phosphocholine cytidylyltransferase alpha is found immediately upstream
      cholinephosphotransferase, and it translocates from a soluble nuclear location to
      the nuclear membrane in response to activators of the CDP-choline pathway. Thus,
      substrate channeling of the CDP-choline produced by CTP:phosphocholine
      cytidylyltransferase alpha to nuclear located CEPT1 is the mechanism by which
      upregulation of the CDP-choline pathway increases de novo phosphatidylcholine
      biosynthesis. In addition, a series of CEPT1 site-directed mutants was generated
      that allowed for the assignment of specific amino acid residues as structural
      requirements that directly alter either phospholipid head group or fatty acyl
      composition. This pinpointed glycine 156 within the catalytic motif as being
      responsible for the dual CDP-alcohol specificity of CEPT1, whereas mutations
      within helix 214-228 allowed for the orientation of transmembrane helices
      surrounding the catalytic site to be definitively positioned.

PMID- 12221123
TI  - An essential subfamily of Drs2p-related P-type ATPases is required for protein
      trafficking between Golgi complex and endosomal/vacuolar system.
AB  - The Saccharomyces cerevisiae genome contains five genes encoding P-type ATPases
      that are potential aminophospholipid translocases (APTs): DRS2, NEO1, and three
      uncharacterized open reading frames that we have named DNF1, DNF2, and DNF3 for
      DRS2/NEO1 family. NEO1 is the only essential gene in APT family and seems to be
      functionally distinct from the DRS2/DNF genes. The drs2Delta dnf1Delta dnf2Delta
      dnf3Delta quadruple mutant is inviable, although any one member of this group can
      maintain viability, indicating that there is a substantial functional overlap
      between the encoded proteins. We have previously implicated Drs2p in clathrin
      function at the trans-Golgi network. In this study, we constructed strains
      carrying all possible viable combinations of null alleles from this group and
      analyzed them for defects in protein transport. The drs2Delta dnf1Delta mutant
      grows slowly, massively accumulates intracellular membranes, and exhibits a
      substantial defect in the transport of alkaline phosphatase to the vacuole.
      Transport of carboxypeptidase Y to the vacuole is also perturbed, but to a lesser
      extent. In addition, the dnf1Delta dnf2Delta dnf3Delta mutant exhibits a defect
      in recycling of GFP-Snc1p in the early endocytic-late secretory pathways. Drs2p
      and Dnf3p colocalize with the trans-Golgi network marker Kex2p, whereas Dnf1p and
      Dnf2p seem to localize to the plasma membrane and late exocytic or early
      endocytic membranes. We propose that eukaryotes express multiple APT subfamily
      members to facilitate protein transport in multiple pathways.

PMID- 12221124
TI  - Regulation of focal adhesion kinase by a novel protein inhibitor FIP200.
AB  - Focal adhesion kinase (FAK) is a major mediator of integrin signaling pathways.
      The mechanisms of regulation of FAK activity and its associated cellular
      functions are not very well understood. Here, we present data suggesting that a
      novel protein FIP200 functions as an inhibitor for FAK. We show the association
      of endogenous FIP200 with FAK, which is decreased upon integrin-mediated cell
      adhesion concomitant with FAK activation. In vitro- and in vivo-binding studies
      indicate that FIP200 interacts with FAK through multiple domains directly. FIP200
      bound to the kinase domain of FAK inhibited its kinase activity in vitro and its
      autophosphorylation in vivo. Overexpression of FIP200 or its segments inhibited
      cell spreading, cell migration, and cell cycle progression, which correlated with
      their inhibition of FAK activity in vivo. The inhibition of these cellular
      functions by FIP200 could be rescued by coexpression of FAK. Last, we show that
      disruption of the functional interaction between endogenous FIP200 with FAK leads
      to increased FAK phosphorylation and partial restoration of cell cycle
      progression in cells plated on poly-L-lysine, providing further support for
      FIP200 as a negative regulator of FAK. Together, these results identify FIP200 as
      a novel protein inhibitor for FAK.

PMID- 12221125
TI  - The product of the survival of motor neuron (SMN) gene is a human telomerase
      associated protein.
AB  - Telomerase is a ribonucleoprotein (RNP) complex that is minimally composed of a
      protein catalytic subunit, the telomerase reverse transcriptase (TERT), and an
      RNA component, the telomerase RNA. The survival of motor neuron (SMN) gene codes
      for a protein involved in the biogenesis of certain RNPs. Here, we report that
      SMN is a telomerase-associated protein. Using in vitro binding assays and
      immunoprecipitation experiments, we demonstrate an association between SMN and
      the telomerase RNP in vitro and in human cells. The specific immunopurification
      of SMN from human 293 cells copurified telomerase activity, suggesting that SMN
      associates with a subset of the functional telomerase holoenzyme. Our results
      also indicate that the human telomerase RNA and the human (h) TERT are not
      associated with Sm proteins, in contrast to Saccharomyces cerevisiae telomerase.
      Immunofluorescence analysis showed that hTERT does not specifically colocalize
      with wild-type SMN in gems or Cajal bodies. However, a dominant-negative mutant
      of SMN (SMNDeltaN27) previously characterized to elicit the cellular
      reorganization of small nuclear RNPs caused the accumulation of hTERT in specific
      SMNDeltaN27-induced cellular bodies. Furthermore, coexpression of SMNDeltaN27 and
      hTERT in rabbit reticulocyte lysates decreased the efficiency of human telomerase
      reconstitution in vitro. Our results establish SMN as a novel telomerase
      associated protein that is likely to function in human telomerase biogenesis.

PMID- 12221126
TI  - alpha4beta1 integrin regulates lamellipodia protrusion via a focal complex/focal
      adhesion-independent mechanism.
AB  - alpha4beta1 integrin plays an important role in cell migration. We show that when
      ectopically expressed in Chinese hamster ovary cells, alpha4beta1 is sufficient
      and required for promoting protrusion of broad lamellipodia in response to
      scratch-wounding, whereas alpha5beta1 does not have this effect. By time-lapse
      microscopy of cells expressing an alpha4/green fluorescent protein fusion
      protein, we show that alpha4beta1 forms transient puncta at the leading edge of
      cells that begin to protrude lamellipodia in response to scratch-wounding. The
      cells expressing a mutant alpha4/green fluorescent protein that binds paxillin at
      a reduced level had a faster response to scratch-wounding, forming alpha4
      positive puncta and protruding lamellipodia much earlier. While enhancing
      lamellipodia protrusion, this mutation reduces random motility of the cells in
      Transwell assays, indicating that lamellipodia protrusion and random motility are
      distinct types of motile activities that are differentially regulated by
      interactions between alpha4beta1 and paxillin. Finally, we show that, at the
      leading edge, alpha4-positive puncta and paxillin-positive focal
      complexes/adhesions do not colocalize, but alpha4beta1 and paxillin colocalize
      partially in ruffles. These findings provide evidence for a specific role of
      alpha4beta1 in lamellipodia protrusion that is distinct from the motility
      promoting functions of alpha5beta1 and other integrins that mediate cell adhesion
      and signaling events through focal complexes and focal adhesions.

PMID- 12221127
TI  - Regulation of airway tight junctions by proinflammatory cytokines.
AB  - Epithelial tight junctions (TJs) provide an important route for passive
      electrolyte transport across airway epithelium and provide a barrier to the
      migration of toxic materials from the lumen to the interstitium. The possibility
      that TJ function may be perturbed by airway inflammation originated from studies
      reporting (1) increased levels of the proinflammatory cytokines interleukin-8 (IL
      8), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and IL
      1beta in airway epithelia and secretions from cystic fibrosis (CF) patients and
      (2) abnormal TJ strands of CF airways as revealed by freeze-fracture electron
      microscopy. We measured the effects of cytokine exposure of CF and non-CF well
      differentiated primary human airway epithelial cells on TJ properties, including
      transepithelial resistance, paracellular permeability to hydrophilic solutes, and
      the TJ proteins occludin, claudin-1, claudin-4, junctional adhesion molecule, and
      ZO-1. We found that whereas IL-1beta treatment led to alterations in TJ ion
      selectivity, combined treatment of TNF-alpha and IFN-gamma induced profound
      effects on TJ barrier function, which could be blocked by inhibitors of protein
      kinase C. CF bronchi in vivo exhibited the same pattern of expression of TJ
      associated proteins as cultures exposed in vitro to prolonged exposure to TNF
      alpha and IFN-gamma. These data indicate that the TJ of airway epithelia exposed
      to chronic inflammation may exhibit parallel changes in the barrier function to
      both solutes and ions.

PMID- 12221128
TI  - Centrosomal proteins CG-NAP and kendrin provide microtubule nucleation sites by
      anchoring gamma-tubulin ring complex.
AB  - Microtubule assembly is initiated by the gamma-tubulin ring complex (gamma-TuRC).
      In yeast, the microtubule is nucleated from gamma-TuRC anchored to the amino
      terminus of the spindle pole body component Spc110p, which interacts with
      calmodulin (Cmd1p) at the carboxy-terminus. However, mammalian protein that
      anchors gamma-TuRC remains to be elucidated. A giant coiled-coil protein, CG-NAP
      (centrosome and Golgi localized PKN-associated protein), was localized to the
      centrosome via the carboxyl-terminal region. This region was found to interact
      with calmodulin by yeast two-hybrid screening, and it shares high homology with
      the carboxyl-terminal region of another centrosomal coiled-coil protein, kendrin.
      The amino-terminal region of either CG-NAP or kendrin indirectly associated with
      gamma-tubulin through binding with gamma-tubulin complex protein 2 (GCP2) and/or
      GCP3. Furthermore, endogenous CG-NAP and kendrin were coimmunoprecipitated with
      each other and with endogenous GCP2 and gamma-tubulin, suggesting that CG-NAP and
      kendrin form complexes and interact with gamma-TuRC in vivo. These proteins were
      localized to the center of microtubule asters nucleated from isolated
      centrosomes. Pretreatment of the centrosomes by antibody to CG-NAP or kendrin
      moderately inhibited the microtubule nucleation; moreover, the combination of
      these antibodies resulted in stronger inhibition. These results imply that CG-NAP
      and kendrin provide sites for microtubule nucleation in the mammalian centrosome
      by anchoring gamma-TuRC.

PMID- 12221130
TI  - Agonist-induced PIP(2) hydrolysis inhibits cortical actin dynamics: regulation at
      a global but not at a micrometer scale.
AB  - Phosphatidylinositol 4, 5-bisphosphate (PIP(2)) at the inner leaflet of the
      plasma membrane has been proposed to locally regulate the actin cytoskeleton.
      Indeed, recent studies that use GFP-tagged pleckstrin homology domains (GFP-PH)
      as fluorescent PIP(2) sensors suggest that this lipid is enriched in membrane
      microdomains. Here we report that this concept needs revision. Using three
      distinct fluorescent GFP-tagged pleckstrin homology domains, we show that highly
      mobile GFP-PH patches colocalize perfectly with various lipophilic membrane dyes
      and, hence, represent increased lipid content rather than PIP(2)-enriched
      microdomains. We show that bright patches are caused by submicroscopical folds
      and ruffles in the membrane that can be directly visualized at approximately 15
      nm axial resolution with a novel numerically enhanced imaging method. F-actin
      motility is inhibited significantly by agonist-induced PIP(2) breakdown, and it
      resumes as soon as PIP(2) levels are back to normal. Thus, our data support a
      role for PIP(2) in the regulation of cortical actin, but they challenge a model
      in which spatial differences in PIP(2) regulation of the cytoskeleton exist at a
      micrometer scale.

PMID- 12221129
TI  - DNA repair and transcriptional effects of mutations in TFIIH in Drosophila
      development.
AB  - Mutations in XPB and XPD TFIIH helicases have been related with three hereditary
      human disorders: xeroderma pigmentosum, Cockayne syndrome, and
      trichothiodystrophy. The dual role of TFIIH in DNA repair and transcription makes
      it difficult to discern which of the mutant TFIIH phenotypes is due to defects in
      any of these different processes. We used haywire (hay), the Drosophila XPB
      homolog, to dissect this problem. Our results show that when hay dosage is
      affected, the fly shows defects in structures that require high levels of
      transcription. We found a genetic interaction between hay and cdk7, and we
      propose that some of these phenotypes are due to transcriptional deficiencies. We
      also found more apoptotic cells in imaginal discs and in the CNS of hay mutant
      flies than in wild-type flies. Because this abnormal level of apoptosis was not
      detected in cdk7 flies, this phenotype could be related to defects in DNA repair.
      In addition the apoptosis induced by p53 Drosophila homolog (Dmp53) is suppressed
      in heterozygous hay flies.

PMID- 12221131
TI  - A Rab8-specific GDP/GTP exchange factor is involved in actin remodeling and
      polarized membrane transport.
AB  - The mechanisms mediating polarized delivery of vesicles to cell surface domains
      are poorly understood in animal cells. We have previously shown that expression
      of Rab8 promotes the formation of new cell surface domains through reorganization
      of actin and microtubules. To unravel the function of Rab8, we used the yeast two
      hybrid system to search for potential Rab8-specific activators. We identified a
      coil-coiled protein (Rabin8), homologous to the rat Rabin3 that stimulated
      nucleotide exchange on Rab8 but not on Rab3A and Rab5. Furthermore, we show that
      rat Rabin3 has exchange activity on Rab8 but not on Rab3A, supporting the view
      that rat Rabin3 is the rat equivalent of human Rabin8. Rabin8 localized to the
      cortical actin and expression of Rabin8 resulted in remodeling of actin and the
      formation of polarized cell surface domains. Activation of PKC by phorbol esters
      enhanced translocation of both Rabin8 and Rab8-specific vesicles to the outer
      edge of lamellipodial structures. Moreover, coexpression of Rabin8 with dominant
      negative Rab8 (T22N) redistributes Rabin8 from cortical actin to Rab8-specific
      vesicles and promotes their polarized transport to cell protrusions. The C
      terminal region of Rabin8 plays an essential role in this transport. We propose
      that Rabin8 is a Rab8-specific activator that is connected to processes that
      mediate polarized membrane traffic to dynamic cell surface structures.

PMID- 12221132
TI  - Calcineurin, a calcium/calmodulin-dependent protein phosphatase, is involved in
      movement, fertility, egg laying, and growth in Caenorhabditis elegans.
AB  - Calcineurin is a Ca(2+)-calmodulin-dependent serine/threonine protein phosphatase
      that has been implicated in various signaling pathways. Here we report the
      identification and characterization of calcineurin genes in Caenorhabditis
      elegans (cna-1 and cnb-1), which share high homology with Drosophila and
      mammalian calcineurin genes. C. elegans calcineurin binds calcium and functions
      as a heterodimeric protein phosphatase establishing its biochemical conservation
      in the nematode. Calcineurin is expressed in hypodermal seam cells, body-wall
      muscle, vulva muscle, neuronal cells, and in sperm and the spermatheca. cnb-1
      mutants showed pleiotropic defects including lethargic movement and delayed egg
      laying. Interestingly, these characteristic defects resembled phenotypes observed
      in gain-of-function mutants of unc-43/Ca(2+)-calmodulin-dependent protein kinase
      II (CaMKII) and goa-1/G(o)-protein alpha-subunit. Double mutants of cnb-1 and unc
      43(gf) displayed an apparent synergistic severity of movement and egg-laying
      defects, suggesting that calcineurin may have an antagonistic role in CaMKII
      regulated phosphorylation signaling pathways in C. elegans.

PMID- 12221133
TI  - Membrane trafficking of heterotrimeric G proteins via the endoplasmic reticulum
      and Golgi.
AB  - Membrane targeting of G-protein alphabetagamma heterotrimers was investigated in
      live cells by use of Galpha and Ggamma subunits tagged with spectral mutants of
      green fluorescent protein. Unlike Ras proteins, Gbetagamma contains a single
      targeting signal, the CAAX motif, which directed the dimer to the endoplasmic
      reticulum. Endomembrane localization of farnesylated Ggamma(1), but not
      geranylgeranylated Ggamma(2), required carboxyl methylation. Targeting of the
      heterotrimer to the plasma membrane (PM) required coexpression of all three
      subunits, combining the CAAX motif of Ggamma with the fatty acyl modifications of
      Galpha. Galpha associated with Gbetagamma on the Golgi and palmitoylation of
      Galpha was required for translocation of the heterotrimer to the PM. Thus, two
      separate signals, analogous to the dual-signal targeting mechanism of Ras
      proteins, cooperate to target heterotrimeric G proteins to the PM via the
      endomembrane.

PMID- 12221134
TI  - Regulation of flagellar dynein by calcium and a role for an axonemal calmodulin
      and calmodulin-dependent kinase.
AB  - Ciliary and flagellar motility is regulated by changes in intraflagellar calcium.
      However, the molecular mechanism by which calcium controls motility is unknown.
      We tested the hypothesis that calcium regulates motility by controlling dynein
      driven microtubule sliding and that the central pair and radial spokes are
      involved in this regulation. We isolated axonemes from Chlamydomonas mutants and
      measured microtubule sliding velocity in buffers containing 1 mM ATP and various
      concentrations of calcium. In buffers with pCa > 8, microtubule sliding velocity
      in axonemes lacking the central apparatus (pf18 and pf15) was reduced compared
      with that of wild-type axonemes. In contrast, at pCa4, dynein activity in pf18
      and pf15 axonemes was restored to wild-type level. The calcium-induced increase
      in dynein activity in pf18 axonemes was inhibited by antagonists of calmodulin
      and calmodulin-dependent kinase II. Axonemes lacking the C1 central tubule (pf16)
      or lacking radial spoke components (pf14 and pf17) do not exhibit calcium-induced
      increase in dynein activity in pCa4 buffer. We conclude that calcium regulation
      of flagellar motility involves regulation of dynein-driven microtubule sliding,
      that calmodulin and calmodulin-dependent kinase II may mediate the calcium
      signal, and that the central apparatus and radial spokes are key components of
      the calcium signaling pathway.

PMID- 12221135
TI  - Analysis of Sec22p in endoplasmic reticulum/Golgi transport reveals cellular
      redundancy in SNARE protein function.
AB  - Membrane-bound soluble N-ethylmaleimide-sensitive factor attachment protein
      receptor (SNARE) proteins form heteromeric complexes that are required for
      intracellular membrane fusion and are proposed to encode compartmental
      specificity. In yeast, the R-SNARE protein Sec22p acts in transport between the
      endoplasmic reticulum (ER) and Golgi compartments but is not essential for cell
      growth. Other SNARE proteins that function in association with Sec22p (i.e.,
      Sed5p, Bos1p, and Bet1p) are essential, leading us to question how transport
      through the early secretory pathway is sustained in the absence of Sec22p. In
      wild-type strains, we show that Sec22p is directly required for fusion of ER
      derived vesicles with Golgi acceptor membranes. In sec22Delta strains, Ykt6p, a
      related R-SNARE protein that operates in later stages of the secretory pathway,
      is up-regulated and functionally substitutes for Sec22p. In vivo combination of
      the sec22Delta mutation with a conditional ykt6-1 allele results in lethality,
      consistent with a redundant mechanism. Our data indicate that the requirements
      for specific SNARE proteins in intracellular membrane fusion are less stringent
      than appreciated and suggest that combinatorial mechanisms using both upstream
      targeting elements and SNARE proteins are required to maintain an essential level
      of compartmental organization.

PMID- 12221136
TI  - Proteasome regulates the delivery of LDL receptor-related protein into the
      degradation pathway.
AB  - The low-density lipoprotein receptor (LDLR)-related protein (LRP) is a
      multiligand endocytic receptor that has broad cellular and physiological
      functions. Previous studies have shown that both tyrosine-based and di-leucine
      motifs within the LRP cytoplasmic tail are responsible for mediating its rapid
      endocytosis. Little is known, however, about the mechanism by which LRP is
      targeted for degradation. By examining both endogenous full-length and a
      minireceptor form of LRP, we found that proteasomal inhibitors, MG132 and
      lactacystin, prolong the cellular half-life of LRP. The presence of proteasomal
      inhibitors also significantly increased the level of LRP at the cell surface,
      suggesting that the delivery of LRP to the degradation pathway was blocked at a
      compartment from which recycling of the receptor to the cell surface still
      occurred. Immunoelectron microscopy analyses demonstrated a proteasomal inhibitor
      dependent reduction in LRP minireceptor within both limiting membrane and
      internal vesicles of the multivesicular bodies, which are compartments that lead
      to receptor degradation. In contrast to the growth hormone receptor, we found
      that the initial endocytosis of LRP minireceptor does not require a functional
      ubiquitin-proteasome system. Finally, using truncated cytoplasmic mutants of LRP
      minireceptors, we found that a region of 19 amino acids within the LRP tail is
      required for proteasomal regulation. Taken together our results provide strong
      evidence that the cellular turnover of a cargo receptor, i.e., LRP, is regulated
      by the proteasomal system, suggesting a broader function of the proteasome in
      regulating the trafficking of receptors into the degradation pathway.

PMID- 12221137
TI  - A Ypt32p exchange factor is a putative effector of Ypt1p.
AB  - Ypt1p regulates vesicle tethering and fusion events from the ER to the Golgi and
      through the early Golgi. Genetic studies have suggested a functional relationship
      between Ypt1p and Ypt31p/Ypt32p. Ypt31p and Ypt32p are a pair of functionally
      redundant GTPases that act after Ypt1p to mediate intra-Golgi traffic or the
      budding of post-Golgi vesicles from the trans-Golgi. Here we report that a novel
      Ypt32p exchange factor is a putative effector of Ypt1p. These findings implicate
      small GTP-binding proteins of the Ypt/Rab family in a signal cascade that directs
      membrane traffic through the secretory pathway.

PMID- 12221138
TI  - Purification and identification of secernin, a novel cytosolic protein that
      regulates exocytosis in mast cells.
AB  - After permeabilization with the pore-forming toxin streptolysin-O mast cells can
      be triggered to secrete by addition of both calcium and a GTP analogue. If
      stimulation is delayed after permeabilization, there is a progressive decrease in
      the extent of secretion upon stimulation, eventually leading to a complete loss
      of the secretory response. This loss of secretory response can be retarded by the
      addition of cytosol from other secretory tissues, demonstrating that the response
      is dependent on a number of cytosolic proteins. We have used this as the basis of
      a bioassay to purify Secernin 1, a novel 50-kDa cytosolic protein that appears to
      be involved in the regulation of exocytosis from peritoneal mast cells. Secernin
      1 increases both the extent of secretion and increases the sensitivity of mast
      cells to stimulation with calcium.

PMID- 12221140
TI  - How loss of meaning with preservation of phonological word form affects immediate
      serial recall performance: a linguistic account.
AB  - We present HP, a patient who following the occurrence of herpes simplex
      encephalitis, lost the ability to understand a subset of words while others
      remained preserved. Of particular interest is the fact that the meaningless items
      retained their lexical status. HP's immediate serial recall of meaningless words
      was thus compared with that of meaningful words to assess the unique contribution
      of semantic knowledge without the confounding influence of phonological word
      (lexical) form. The results revealed a clear recall advantage for meaningful over
      meaningless words, indicating a specific contribution to recall from the semantic
      level of representation. Furthermore, an error analysis showed that phonemic
      errors were most common when semantic information was lacking. Interestingly, the
      same error pattern was found for pseudo-words that shared phonological elements
      with meaningless words. These findings support a linguistic and interactive
      activation account of short-term serial recall, which assumes that all levels of
      representation, including semantic knowledge about words, contribute to recall
      performance. In addition, the findings provide preliminary evidence that this
      view may be extended to the recall of pseudo-words, as there appear to be some
      influences of semantic representation on pseudo-word recall.

PMID- 12221139
TI  - Role of LAMP-2 in lysosome biogenesis and autophagy.
AB  - In LAMP-2-deficient mice autophagic vacuoles accumulate in many tissues,
      including liver, pancreas, muscle, and heart. Here we extend the phenotype
      analysis using cultured hepatocytes. In LAMP-2-deficient hepatocytes the half
      life of both early and late autophagic vacuoles was prolonged as evaluated by
      quantitative electron microscopy. However, an endocytic tracer reached the
      autophagic vacuoles, indicating delivery of endo/lysosomal constituents to
      autophagic vacuoles. Enzyme activity measurements showed that the trafficking of
      some lysosomal enzymes to lysosomes was impaired. Immunoprecipitation of
      metabolically labeled cathepsin D indicated reduced intracellular retention and
      processing in the knockout cells. The steady-state level of 300-kDa mannose 6
      phosphate receptor was slightly lower in LAMP-2-deficient hepatocytes, whereas
      that of 46-kDa mannose 6-phosphate receptor was decreased to 30% of controls due
      to a shorter half-life. Less receptor was found in the Golgi region and in
      vesicles and tubules surrounding multivesicular endosomes, suggesting impaired
      recycling from endosomes to the Golgi. More receptor was found in autophagic
      vacuoles, which may explain its shorter half-life. Our data indicate that in
      hepatocytes LAMP-2 deficiency either directly or indirectly leads to impaired
      recycling of 46-kDa mannose 6-phosphate receptors and partial mistargeting of a
      subset of lysosomal enzymes. Autophagic vacuoles may accumulate due to impaired
      capacity for lysosomal degradation.

PMID- 12221141
TI  - A third route for reading? Implications from a case of phonological dyslexia.
AB  - Models of reading in the neuropsychological literature sometimes only include two
      routes from print to sound, a lexical semantic route and a sublexical
      phonological route. Other researchers hypothesize an additional route that
      involves a direct connection between lexical orthographic representations and
      lexical phonological representations. This so-called 'third route' has been
      invoked to account for the preserved oral reading of some patients who show
      severe semantic impairments and a disruption of the sublexical phonological
      route. In their summation hypothesis, Hillis and Caramazza proposed that reading
      in these cases could result from a combination of partial lexical semantic
      information and partial sublexical phonological information, thus obviating the
      need for the third route. The present study examined the case of a phonological
      dyslexic patient (ML) who exhibited preserved word reading, even for items he
      could not name, along with a non-word reading impairment. The relationship
      between ML's naming and reading, and the influence of semantic variables on his
      reading were examined. The results of this examination are interpreted as
      supporting the existence of the third route.

PMID- 12221142
TI  - Agnosia for object orientation: naming and mental rotation evidence.
AB  - We have previously reported the performance of a patient (NL) who could recognize
      objects, but appeared to lack knowledge of their orientation. These results were
      interpreted as evidence that NL had isolated access to a viewpoint-independent
      (ventral stream) object recognition system. However, because NL's responses on
      naming tasks were not timed, it was not possible to establish whether he showed
      the same pattern of reaction time performance generally accepted as evidence of a
      'mental rotation' strategy in neurologically normal subjects. Here we report NL's
      performance on two reaction time tasks, testing his ability to transform images
      when naming, and discriminating between rotated mirror image objects. As
      predicted, and in contrast to normal volunteers, NL showed no 'mental rotation'
      effect in his naming of misoriented objects. Paradoxically, he performed well on
      a traditional Shepard and Metzler mental rotation task. He also showed a normal
      orientation effect when dealing with misoriented faces. These findings offer
      further support for viewpoint-independent theories of object recognition, and
      bolster the claim that object orientation knowledge can be regarded as, in some
      respects, a special class of spatial information.

PMID- 12221143
TI  - First saccades reveal biases in recovered neglect.
AB  - Hemispatial neglect affects the ability to explore space on the side opposite a
      brain lesion. This deficit is also mirrored in abnormal saccadic eye movement
      patterns. The present study investigated if the recovery of neglect is also
      reflected in saccadic eye movements. Patient AF, who displayed strong hemispatial
      neglect 1 month post-right thalamic stroke, had largely recovered 3 months later
      when tested on visual exploration tasks of the Behavioural Inattention Test. At
      this stage, AF was tested on a visual search task while his eye movements
      (direction, latencies and amplitudes of first saccades) and manual reaction times
      were recorded. The experimental conditions differed with respect to stimulus
      number and distracter type and increased in difficulty. AF correctly generated
      saccades into the neglected field when the target was presented alone. In
      contrast, a considerable left/right difference was present for all multiple
      stimulus search displays. Although recovered from neglect in standardized
      assessment, AF showed a strong rightward bias resulting in highly asymmetric
      response times and eye movement behaviour. We conclude that eye movement patterns
      are far more susceptible to remaining spatial impairments and can thus provide a
      sensitive means to assess the extent of neglect recovery.

PMID- 12221144
TI  - A case of impaired auditory and visual speech prosody perception after right
      hemisphere damage.
AB  - It is well established that vision plays a role in segmental speech perception,
      but the role of vision in prosodic speech perception is less clear. We report on
      the difficulties in prosodic speech perception encountered by KB after a right
      hemisphere stroke. In addition to musical deficits, KB was suspected of having
      impaired auditory prosody perception. As expected, KB was impaired on two prosody
      perception tasks in an auditory-only condition. We also examined whether the
      addition of visual prosody cues would facilitate his performance on these tasks.
      Unexpectedly, KB was also impaired on both tasks under visual-only and audio
      visual conditions. Thus, there was no evidence that KB could integrate auditory
      and visual prosody information or that he could use visual cues to compensate for
      his deficit in the auditory domain. In contrast, KB was able to identify
      segmental speech information using visual cues and to use these visual cues to
      improve his performance when auditory segmental cues were impoverished. KB was
      also able to integrate audio-visual segmental information in the McGurk effect.
      Thus, KB's visual deficit was specific to prosodic speech perception and, to our
      knowledge, this is the first reported case of such a deficit.

PMID- 12221145
TI  - Visuospatial hemi-inattention following cerebellar/brain stem bleeding.
AB  - Neglect is a unilateral lack of responsiveness to stimuli caused by visuospatial
      hemi-inattention, a unilateral representation deficit and/or a unilateral
      hypokinesia. It results most frequently from right-hemisphere brain damage,
      particularly of the parietal lobe but also of the frontal cortex, the basal
      ganglia, the thalamus, and recently it has also been described after a cerebellar
      lesion. We report a patient with right-sided bleeding of the posterior inferior
      cerebellar artery, who developed a left-sided visual hemi-inattention. She had no
      visual field defects, yet she had problems detecting left-sided targets in visual
      extinction. Furthermore, she was impaired in detecting complex motion on the left
      side and targets in a fixation offset paradigm. Reactions to left-sided targets
      in covert shifts of attention were slowed in the invalid condition. Her text
      reading was impaired as she could not always find the initial word of the next
      line. However, she was aware of her deficit. Her visuoconstructive ability was
      normal and she gave no indication of tactile or acoustic extinction. As the
      cerebellar lesion was located in the right hemisphere and the inattention
      involved the left side of space, we suggest that the damage to the right brain
      stem led to a transient imbalance of the noradrenergic ascending activation
      system which may explain her hemi-inattention.

PMID- 12221146
TI  - Numbers and letters: exploring an autistic savant's unpracticed ability.
AB  - This paper describes an individual with autism and high-level calendar
      calculation ability who could perform a set of unpracticed letter/number
      association tasks. The savant's performance was compared with that of two control
      participants, one a departmental secretary and the other a professor of
      mathematics. The facility with which the savant could master the rules governing
      the relationships between the series of items suggests that he possessed a
      flexibility of mental processing transcending his ability of calendar
      calculation. Furthermore, he could recalibrate previous knowledge to solve new
      hitherto unpracticed tasks. When presented with novel problems, the savant,
      unlike the mathematician, made no initial errors at all on any of the presented
      tasks, thereby indicating his fast and spontaneous recognition of new rules and
      of new relationships between items. It is concluded that a cognitive style of
      'weak central coherence' as adopted by autistic savants may protect single
      representations from being retained in the form of stable enduring wholes, and
      that such a segmentation strategy may allow for the transformation,
      reorganization and reconstruction of the relationship between single items of
      information.

PMID- 12221147
TI  - Synaesthesia: a case study of discordant monozygotic twins.
AB  - We describe a study of 11-year-old twin sisters who are physically identical in
      appearance but who have considerably different conscious experiences. One twin
      appears to be a synaesthete in that she states that she has specific colour
      experiences (i.e. photisms) whenever she views, hears or thinks of digits. The
      other twin does not report such conscious experiences when viewing, hearing or
      thinking about digits. A genotypic analysis using eight microsatellite loci plus
      the gender of the twins and their parents confirmed that the twins are
      monozygotic. A phenotypic analysis using a modification of the Stroop task
      confirmed that only one twin is a synaesthete. We suggest that the discordance in
      synaesthesia may be due to either an epigenetic event, X chromosome inactivation,
      or a mutation of a synaesthesia gene.

PMID- 12221149
TI  - Mechanisms of pain modulation in chronic syndromes.
AB  - Transmission of pain from the periphery to the cortex depends on integration and
      signal processing within the spinal cord, brainstem, and forebrain.
      Sensitization, a component of persistent or chronic pain, may develop either
      through peripheral mechanisms or as a consequence of altered physiology in the
      spinal cord or forebrain. Several molecular and biophysical mechanisms contribute
      to the phenomenon of sensitization and persistent pain, including upregulation of
      sensory neuron-specific sodium channels and vanilloid receptors, phenotypic
      switching of large myelinated axons, sprouting within the dorsal horn, and loss
      of inhibitory neurons due to apoptotic cell death. Recently, forebrain structures
      have been implicated in the pathophysiology of persistent pain. Although a number
      of treatment options are used, unfortunately pharmacotherapy for neuropathic pain
      is often ineffective. Unraveling the mysteries of chronic pain may lead to better
      treatment options, such as drugs that act specifically on sensory neuron-specific
      sodium channels or as NR2B-subunit-selective N-methyl-D-aspartate receptor
      antagonists.

PMID- 12221150
TI  - Chronic headache: New advances in treatment strategies.
AB  - Chronic daily headache (CDH) affects approximately 4 to 5% of the population and
      encompasses a number of different diagnoses, including transformed migraine,
      chronic tension-type headache (TTH), new-onset daily persistent headache, and
      hemicrania continua. Although the pathophysiology of CDH is still poorly
      understood, some research has suggested that each of the various subtypes of CDH
      may have a different pathogenesis. The goals of prophylactic therapy are to
      reduce the frequency, severity, and duration of headache attacks; to improve
      responsiveness to treatment of acute attacks; to improve function; and to reduce
      disability. However, opinions differ as to exactly which are the best and most
      appropriate outcome measures for prophylaxis. Several pharmacologic treatment
      options exist, including antidepressants, anticonvulsants, muscle relaxants,
      serotonin agonists, ergots, serotonin antagonists, antianxiety agents, and other
      miscellaneous drugs. Tizanidine, an alpha(2)-adrenergic agonist, has recently
      emerged as a promising prophylactic adjunct for CDH, which implicates a central
      alpha(2)-adrenergic mechanism as an important factor in the pathophysiology of
      CDH.

PMID- 12221151
TI  - Use of anticonvulsants for treatment of neuropathic pain.
AB  - Emerging evidence from animal models of neuropathic pain suggests that many
      pathophysiologic and biochemical changes occur in the peripheral and central
      nervous system. Similarities between the pathophysiologic phenomena observed in
      some epilepsy models and in neuropathic pain models justify the use of
      anticonvulsants in the symptomatic management of neuropathic pain. Positive
      results from laboratory and clinical trials further support such use.
      Carbamazepine was the first of this class of drugs to be studied in clinical
      trials and has been longest in use for treatment of neuropathic pain. Clinical
      trial data support its use in treating trigeminal neuralgia, but data for
      treatment of painful diabetic neuropathy are less convincing. Use of newer
      anticonvulsants has marked a new era in the treatment of neuropathic pain.
      Gabapentin has demonstrated efficacy, specifically in painful diabetic neuropathy
      and postherpetic neuralgia. Lamotrigine has been reported to be effective in
      relieving pain from trigeminal neuralgia refractory to other treatments, HIV
      neuropathy, and central post-stroke pain. Results from clinical trials of
      phenytoin are equivocal. Zonisamide's mechanisms of action suggest that it would
      be effective in controlling neuropathic pain symptoms. Other anticonvulsants,
      including lorazepam, valproate, topiramate, and tiagabine, have also been under
      investigation. Anecdotal experience provides support for studies with
      oxcarbazepine and levetiracetam for treating neuropathic pain. Evidence
      supporting the efficacy of anticonvulsants in treatment of such pain is evolving.
      Additional clinical trials should provide information that will better define
      their role in neuropathic pain.

PMID- 12221152
TI  - Treatment options for refractory pain: the role of intrathecal therapy.
AB  - Intraspinal drug delivery represents an important treatment option for the
      management of chronic pain. Selection of candidates for this type of therapy
      requires careful evaluation of the patient, possibly including psychological
      screening. Although determining the efficacy of long-term intraspinal drug
      therapy has been challenging, several classes of agents have been identified to
      provide benefits in patients with a variety of pain types. Such agents include
      opioids, alpha(2)-agonists, sodium channel antagonists, and gamma-aminobutyric
      acid agonists. In addition, combinations of agents with distinct mechanisms of
      action may be therapeutically advantageous because many clinical pain states
      result from more than one mechanism.

PMID- 12221153
TI  - Late cognitive decline after CABG: inevitable or preventable?

PMID- 12221154
TI  - Multiple sclerosis, depression, and the risk of suicide.

PMID- 12221155
TI  - Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial.
AB  - BACKGROUND: Hyperglycemia during acute ischemic stroke may augment brain injury,
      predispose to intracerebral hemorrhage (ICH), or both. METHOD: To analyze the
      relationship between admission glucose level and clinical outcomes from acute
      ischemic stroke, the authors performed multivariate regression analysis with the
      National Institute of Neurological Disorders and Stroke recombinant tissue
      plasminogen activator (rt-PA) Stroke Trial data. Neurologic improvement was
      defined as improvement on the NIH Stroke Scale by 4 or more points from baseline
      to 3 months, or a final score of zero. Favorable outcome was defined as both
      Glasgow Outcome score of 1 and Barthel Index 95 to 100 at 3 months. Symptomatic
      ICH was defined as CT-documented hemorrhage temporally related to clinical
      deterioration within 36 hours of treatment. Potential confounding factors were
      controlled, including acute treatment (rt-PA or placebo), age, baseline NIH
      Stroke Scale score, history of diabetes mellitus, stroke subtype, and admission
      blood pressure. RESULTS: There were 624 patients enrolled within 3 hours after
      stroke onset. As admission glucose increased, the odds for neurologic improvement
      decreased (odds ratio [OR] = 0.76 per 100 mg/dL increase in admission glucose,
      95% CI 0.61 to 0.95, p = 0.01). The relation between admission glucose and
      favorable outcome depended on admission mean blood pressure (MBP): as admission
      MBP increased, the odds for favorable outcome related to increasing admission
      glucose levels progressively decreased (p = 0.02). As admission glucose
      increased, the odds for symptomatic ICH also increased (OR = 1.75 per 100 mg/dL
      increase in admission glucose, 95% CI 1.11 to 2.78, p = 0.02). Admission glucose
      level was not associated with altered effectiveness of rt-PA. CONCLUSIONS: In
      patients with acute ischemic stroke, higher admission glucose levels are
      associated with significantly lower odds for desirable clinical outcomes and
      significantly higher odds for symptomatic ICH, regardless of rt-PA treatment.
      Whether this represents a cause and effect relationship remains to be determined.

PMID- 12221156
TI  - An examination of suicidal intent in patients with multiple sclerosis.
AB  - OBJECTIVE: To examine neurologic and psychiatric correlates of suicidal intent in
      a community sample of 140 patients with MS. METHODS: Patients with (28.6%) and
      without lifetime suicidal intent were compared across MS disease-related and
      psychiatric variables. All subjects were interviewed with 1) the Structured
      Clinical Interview for DSM-IV Axis 1 disorders (SCID-IV) to determine lifetime
      prevalence of major depression and anxiety disorders; and 2) the Social Stress
      and Support Interview to assess psychological stressors. Suicidal intent was
      documented with questions from the SCID-IV and Beck Suicide Scale. Patients also
      completed the Hospital Anxiety and Depression Scale and cognitive testing.
      RESULTS: Suicidal patients were significantly more likely to live alone, have a
      family history of mental illness, report more social stress, and have lifetime
      diagnoses of major depression, anxiety disorder, comorbid depression-anxiety
      disorder, and alcohol abuse disorder. By logistic regression analysis, the
      severity of major depression, alcohol abuse, and living alone had an 85%
      predictive accuracy for suicidal intent. A third of suicidal patients had not
      received psychological help. Two-thirds of subjects with current major
      depression, all suicidal, had not received antidepressant medication.
      CONCLUSIONS: Suicidal intent, a potential harbinger for suicide, is common in MS
      and is strongly associated with major depression, alcohol abuse, and social
      isolation. Suicidal intent is a potentially treatable cause of morbidity and
      mortality in MS.

PMID- 12221157
TI  - Benefit of interferon beta-1a on MSFC progression in secondary progressive MS.
AB  - BACKGROUND: Interferon beta-1a (IFNbeta-1a, Avonex) is efficacious in relapsing
      forms of MS. Studies of other IFNbeta preparations in secondary progressive MS
      (SPMS) yielded conflicting results. This study was undertaken to determine
      whether IFNbeta-1a slowed disease progression in SP-MS. METHODS: A total of 436
      subjects with SPMS and Expanded Disability Status Scale (EDSS) score 3.5 to 6.5
      were randomized to receive IFNbeta-1a (60 micro g) or placebo by weekly
      intramuscular injection for 2 years. The primary outcome measure, used for the
      first time in a large-scale MS trial, was baseline to month 24 change in the MS
      Functional Composite (MSFC), comprising quantitative tests of ambulation (Timed
      25-Foot Walk), arm function (Nine-Hole Peg Test [9HPT]), and cognition (Paced
      Auditory Serial Addition Test [PASAT]). RESULTS: Median MSFC Z-score change was
      reduced 40.4% in IFNbeta-1a subjects (-0.096 vs -0.161 in placebo subjects, p =
      0.033), an effect driven mainly by the 9HPT and PASAT. There was no discernible
      benefit on the EDSS, which in this range principally reflects walking ability.
      IFNbeta-1a subjects had 33% fewer relapses (p = 0.008). There was significant
      benefit on eight of 11 MS Quality of Life Inventory subscales. New or enlarging
      T2-hyperintense brain MRI lesions and gadolinium-enhancing lesions were reduced
      at months 12 and 24 (both p < 0.001). IFNbeta-1a was well tolerated by the
      majority of subjects. Neutralizing antibodies developed in 3.3% of IFNbeta-1a
      treated subjects. CONCLUSIONS: IFNbeta-1a demonstrated benefit on MSFC
      progression, relapses, quality of life, and MRI activity in SPMS.

PMID- 12221158
TI  - Methylprednisolone effect on brain volume and enhancing lesions in MS before and
      during IFNbeta-1b.
AB  - OBJECTIVE: To determine the effect of IV methylprednisolone (IVMP) on brain
      fraction volume (BFV), contrast-enhancing (CE) lesions, and white matter lesion
      load (WMLL) in patients with relapsing-remitting MS treated for acute
      exacerbations. BACKGROUND: MRI metrics of MS disease activity are being used as
      outcome measures in early phase treatment trials, however the short-term effects
      of IVMP treatment on cerebral atrophy are unknown. METHODS: Serial monthly MRI
      were performed in 26 patients enrolled in a baseline vs treatment trial with
      interferon beta-1b (IFNbeta-1b) who were followed for 3 months before and after
      IVMP. All 26 patients were evaluated while receiving IFNbeta-1b, and 12 patients
      were also studied during the baseline stage of the trial (NHx). Acute
      exacerbations were treated with IVMP (1 g/d) for 3 to 5 days. Precontrast and
      postcontrast T1-weighted and proton density T2-weighted fast spin-echo images
      were analyzed. RESULTS: Fifty-six acute exacerbations were evaluated. For the 3
      months before IVMP, there was no difference in WMLL or BFV compared to month IVMP
      was administered. There was a significant decrease in BFV at month 1 after IVMP
      in the IFNbeta-1b and NHx groups. Compared to the month IVMP was administered,
      there was a difference in the CE lesions for months -3 and -1 prior (p < 0.039)
      in NHx patients. Following IVMP, CE lesions decreased (p < 0.0004) for months 1,
      2, and 3 in both groups, but there was no effect on WMLL. CONCLUSIONS: BFV and CE
      lesions were significantly decreased for 1 month (BFV) and 3 months (CE lesions)
      following IVMP. Therefore, MRI studies should be delayed by probably at least 2
      months following IVMP to avoid a possible confounding steroid effect in a
      clinical trial.

PMID- 12221159
TI  - Huntington's disease: a randomized, controlled trial using the NMDA-antagonist
      amantadine.
AB  - OBJECTIVE: To examine the acute effects of the NMDA receptor antagonist
      amantadine on motor and cognitive function in Huntington's disease (HD).
      BACKGROUND: Chorea in HD and in the levodopa-induced dyskinesias of PD may be
      clinically indistinguishable. In PD, hyperphosphorylation of NMDA receptors
      expressed on striatal medium spiny neurons contributes to peak-dose dyskinesias,
      and drugs that block these receptors can diminish chorea severity. Because these
      spiny neurons are the primary target of the neurodegenerative process in HD,
      sensitization of NMDA receptors on residual striatal neurons might also
      participate in the generation of motor dysfunction in HD. METHODS: To evaluate
      this possibility, 24 patients with HD entered a double-blind placebo-controlled
      crossover study of amantadine with two 2-week arms. RESULTS: Chorea scores were
      lower with amantadine (usually 400 mg/d) than placebo, with a median reduction in
      extremity chorea at rest of 36% (p = 0.04) for all 22 evaluable patients and of
      56% in the 10 individuals with the highest plasma drug levels. Improvement
      correlated with plasma amantadine concentrations (p = 0.01) but not CAG repeat
      length. Parkinsonian rating scores did not worsen and there was no consistent
      change in cognitive measures. Adverse event profile was benign. CONCLUSIONS:
      Results suggest that NMDA receptor supersensitivity may contribute to the
      clinical expression of choreiform dyskinesias in HD and that selective
      antagonists at that site can safely confer palliative benefit.

PMID- 12221160
TI  - Effects of subthalamic nucleus (STN) stimulation on motor cortex excitability.
AB  - BACKGROUND: Deep brain stimulation of the internal global pallidus (GPi) and the
      subthalamic nucleus (STN) has become a treatment alternative in advanced PD.
      Although the effects of GPi stimulation have been examined recently, little is
      known about STN stimulation effects on motor cortex excitability. METHODS: The
      effects of STN stimulation were studied in eight patients with advanced PD using
      paired-pulse transcranial magnetic stimulation (TMS) in comparison with healthy
      control subjects. Motor evoked potentials following paired-pulse TMS
      (interstimulus interval 3 ms to test for corticocortical inhibition vs 13 ms for
      facilitation) have been recorded from the extensor carpi radialis and its
      functional antagonist, the flexor carpi radialis muscle. Silent period (SP) was
      also determined. Patients were examined under four conditions: medication
      "off"/stimulator "off" vs medication "on"/stimulator "off" vs medication
      "off"/stimulator "on" vs medication "on"/stimulator "on." RESULTS: Although the
      mean values for intracortical inhibition (ICI) were not significantly different,
      data variation was smaller and levels of significance higher with the STN
      stimulator switched "on," suggesting that ICI was more consistent. SP during
      stimulator "on"/medication "on" was longer than during stimulator
      "off"/medication "off." Motor performance as indicated by a finger-tapping test
      and Unified PD Rating Scale III was significantly better with dopaminergic
      medication and further improved with stimulator "on." CONCLUSIONS: Results
      suggest an effect of subthalamic nucleus stimulation on intracortical inhibitory
      mechanisms. This hypothesis could at least partially explain a more consistent
      depression of motor evoked potentials following inhibiting paired-pulse
      transcranial magnetic stimulation, a longer silent period (under stimulator
      "on"/medication "on"), and a reduction of akinesia and rigidity leading to a
      better motor performance in subthalamic nucleus-stimulated patients.

PMID- 12221161
TI  - The impact on Parkinson's disease of electrical parameter settings in STN
      stimulation.
AB  - BACKGROUND: The main advantage of deep brain stimulation (DBS) in the treatment
      of PD is that the electrical settings can be adjusted to optimize benefits and
      minimize adverse effects. The main objective of this study was to discover how
      varying these electrical parameters impacted on parkinsonian motor signs.
      METHODS: Twelve patients with PD with chronic bilateral subthalamic nucleus (STN)
      stimulation were selected. The authors evaluated the effects of a variation in
      the voltages, frequencies, and pulse widths on tremor, bradykinesia, and rigidity
      using two different paradigms: one in which the total electrical energy delivered
      was held constant, and one in which this was varied. Up to 26 parameter
      conditions were tested under double blind randomized conditions. RESULTS:
      Voltages >or=3 V and frequencies >or=130 Hz led to the greatest improvement in
      all three parkinsonian signs. A rate of 5 Hz significantly worsened akinesia. The
      combination of the highest voltage with the narrowest pulse width was most
      effective. CONCLUSIONS: This study confirms that the most beneficial effects
      induced by STN stimulation are obtained at high frequencies and that voltage is
      the most critical factor to obtain adequate alteration in STN activity. The
      mechanisms by which STN DBS improves parkinsonism remain speculative.

PMID- 12221162
TI  - Ambulatory blood pressure and brain atrophy in the healthy elderly.
AB  - BACKGROUND: Brain lesions and atrophy increase with age and hypertension.
      OBJECTIVE: To evaluate the relationship of age and ambulatory blood pressure (BP)
      to brain atrophy in healthy elderly individuals. METHODS: MRI volume measurements
      (normalized to intracranial volume) were taken of total brain and lateral and
      third ventricles in 155 healthy men and women who went through extensive medical
      examinations. Younger (56 to 66 years old) and older (67 to 80 years old)
      subgroups were compared on casual and 24-hour ambulatory BP values and MRI volume
      measurements. RESULTS: Older subjects had smaller brain volumes and larger
      lateral and third ventricles. Compared with women, men had larger lateral and
      third ventricles. With age controlled for, greater sleep systolic BP (SBP)
      variability was associated with smaller brain volumes; greater waking and sleep
      SBP variability were associated with larger lateral and third ventricles.
      Subjects with higher casual and waking SBP and waking diastolic BP had larger
      lateral ventricles. Among older subjects, only those with elevated SBP had
      smaller brain volumes and larger lateral ventricles. CONCLUSIONS: These results
      indicate that if BP levels are within the upper normal range, even healthy
      individuals with no prior diagnosis of hypertension are more likely to have brain
      atrophy than those with lower BP. Moreover, not only do BP level and variability
      relate to brain atrophy, but the combination of high level and greater
      variability shows an even stronger relationship to brain atrophy than either one
      of these variables alone.

PMID- 12221163
TI  - The role of the left frontal lobe in action naming: rTMS evidence.
AB  - BACKGROUND: Neuropsychological and neuroimaging studies suggest that whereas the
      left temporal neocortex plays a crucial role in all tasks involving lexical
      semantic processing, some regions of the left prefrontal convexity are
      selectively recruited during verb processing. OBJECTIVE: To determine if there
      are different neural correlates for noun and verb processing in the human brain.
      METHODS: Repetitive transcranial magnetic stimulation (rTMS), 20 Hz at 90% of the
      motor threshold, was applied to left or right prefrontal brain during object- and
      action-naming tasks in nine healthy subjects. RESULTS: A shortening of naming
      latency for actions was observed only after stimulation of left prefrontal
      cortex. CONCLUSION: The involvement of the left dorsolateral frontal cortex in
      action naming was demonstrated using rTMS.

PMID- 12221164
TI  - Association of mu-opioid receptor subunit gene and idiopathic generalized
      epilepsy.
AB  - OBJECTIVE: To replicate and extend the previously reported association between
      the opioid receptor mu subunit gene (OPRM1) and idiopathic absence epilepsy
      (IAE), using a sample of 230 probands with idiopathic generalized epilepsy (IGE).
      BACKGROUND: In humans and in animal models, several lines of evidence implicate
      opioid receptors with seizures. The G118 allele of OPRM1 was associated with IAE
      (p = 0.019). METHODS: Three single nucleotide polymorphisms (SNP) of OPRM1 were
      investigated by association studies with IGE using a case/control design, one of
      which also used a within-family design. RESULTS: Association was found for G118
      with IGE (p = 0.00027, odds ratio [OR] = 1.86), replicating the previous
      association. Within-family tests of linkage and association (haplotype-based
      haplotype relative risk and transmission disequilibrium test) confirmed this
      result. Further evidence for involvement of OPRM1 in IGE was provided by an
      association with G-172T, located in the 5' untranslated region (p = 0.0015, OR =
      2.36). Haplotypes of the two SNPs were associated with IGE with a greater level
      of significance (p = 0.000087) suggesting that both SNPs might be in linkage
      disequilibrium with a single functional variant. Analysis of the results by
      subgroups of IGE showed association with all subgroups tested. CONCLUSIONS: These
      results confirm the previous association and support the hypothesis of a role for
      OPRM1 in IGE, including absence syndromes. However, the authors found no evidence
      for a specific association between OPRM1 and idiopathic absence epilepsy. The
      data suggest that the functional variant predisposing to IGE is located within
      60kb of exon 1.

PMID- 12221165
TI  - Survival in transgenic ALS mice does not vary with CNS glutathione peroxidase
      activity.
AB  - OBJECTIVE: Transgenic mice that overexpress a human gene encoding mutant
      cytosolic superoxide dismutase (SOD1) develop a progressive motor neuron loss
      that resembles human ALS. Why mutant SOD1 initiates motor neuron death is
      unknown. One hypothesis proposes that the mutant molecule has enhanced peroxidase
      activity, reducing hydrogen peroxide (H2O2) to form toxic hydroxyl adducts on
      critical targets. To test this hypothesis, the authors generated transgenic ALS
      mice with altered levels of glutathione peroxidase (GSHPx), the major soluble
      enzyme that detoxifies H2O2. METHODS: SOD1(G93A) ALS mice were bred with mice
      bearing a murine GSHPx transgene that have a four-fold elevation in brain GSHPx
      levels and with mice having targeted inactivation of the GSHPx gene and reduced
      brain GSHPx activity. RESULTS: Survival was not prolonged in ALS mice with
      elevated brain GSHPx activity (p = 0.09). ALS mice with decreased GSHPx brain
      activity (20% of normal) showed no acceleration of the disease course (p = 0.89).
      The age at disease onset in the ALS mice was unaffected by brain GSHPx activity.
      CONCLUSION: The level of GSHPx activity in the CNS of transgenic ALS mice does
      not play a critical role in the development of motor neuron disease.

PMID- 12221166
TI  - Peripheral nervous system in gyrate atrophy of the choroid and retina with
      hyperornithinemia.
AB  - OBJECTIVE: To evaluate peripheral nervous system involvement in gyrate atrophy of
      the choroid and retina with hyperornithinemia (GA). BACKGROUND: GA is an inborn
      error of amino acid metabolism caused by mutations in the enzyme ornithine
      aminotransferase. Patients with GA have hyperornithinemia, progressive
      centripetal loss of vision, minor CNS abnormalities, and type II muscle fiber
      atrophy with accumulation of tubular aggregates. The authors previously showed
      that muscle and brain creatine stores are depleted in the patients with GA.
      METHODS: The authors searched evidence of peripheral nervous involvement in 40
      patients with GA (mean age 31.6 +/- 16.3 years; range 5 to 74 years) by using
      neurography, quantitative sensory threshold testing, and evoked potential
      testing. RESULTS: Neurography revealed abnormalities in 21 (53%) of the patients.
      The abnormalities associated with the severity of the ophthalmologic changes and
      the age of the patients. With quantitative sensory threshold testing, abnormal
      large-fiber function was found in seven (18%) and abnormal small-fiber function
      was found in four (10%) patients. Somatosensory evoked potential and brainstem
      auditory evoked potential responses were abolished in five patients. CONCLUSIONS:
      These findings of peripheral nervous system involvement in GA suggest that GA is
      a systemic disease affecting not only CNS but also the peripheral nervous system.

PMID- 12221167
TI  - Cognitive performance after coronary artery bypass grafting: a follow-up study.
AB  - The authors studied 52 of an initial cohort of 91 patients who underwent coronary
      artery bypass grafting and survived the perioperative period without stroke or
      other comorbidities, after a median follow-up of 55 months. Baseline data of the
      followed patients were comparable to those lost for follow-up. No patient showed
      a decline in neuropsychological test performance as compared to baseline.
      Vascular risk factor control was good in all patients, possibly contributing to
      the favorable outcome.

PMID- 12221168
TI  - Interferon beta1a and depression in secondary progressive MS: data from the
      SPECTRIMS Trial.
AB  - Depression is a suspected side effect of treatment with interferon beta1a in MS.
      However, an association with depression has not been confirmed by rigorous
      studies. During the SPECTRIMS clinical trial of interferon beta1a (Rebif) in
      secondary progressive MS, depression ratings were obtained from 365 subjects
      treated either with interferon beta1a or with placebo. No significant differences
      between groups emerged during 36 months of follow-up. These data suggest that
      depression is not a side effect of interferon beta1a.

PMID- 12221169
TI  - Hippocampal, amygdalar, and global brain atrophy in different apolipoprotein E
      genotypes.
AB  - The epsilon4 allele of the APOE gene increases the risk for AD, whereas the
      epsilon2 allele may be protective. The authors assessed the impact of APOE
      genotype on hippocampal, amygdalar, and global brain atrophy as putative markers
      of preclinical AD in a nondemented population. Carriers of epsilon4 had
      significantly more hippocampal and amygdalar atrophy than epsilon3epsilon3
      subjects, but not more global brain atrophy. Carriers of epsilon2 did not have
      less brain atrophy than epsilon3epsilon3 subjects.

PMID- 12221170
TI  - Reemergence of activation with poststroke somatosensory recovery: a serial fMRI
      case study.
AB  - The authors demonstrate the potential for poststroke return of activation in
      regions normally involved in touch discrimination in a serial, whole-brain fMRI
      study of a patient with marked sensory loss followed by good recovery. A return
      of activation in ipsilesional primary and bilateral secondary somatosensory
      cortices was observed at 3 months after stroke and was maintained at 6 months,
      indicating a reemergence of activation after the interval of somatosensory
      recovery. There was little evidence of neural plastic changes early after stroke
      (2 weeks), when sensory loss was severe.

PMID- 12221171
TI  - Diffusion tensor imaging of periventricular leukomalacia shows affected sensory
      cortex white matter pathways.
AB  - The authors used diffusion-tensor imaging to examine central white matter
      pathways in two children with spastic quadriplegic cerebral palsy. Corticospinal
      tracts projecting from cortex to brainstem resembled controls. In contrast,
      posterior regions of the corpus callosum, internal capsule, and corona radiata
      were markedly reduced, primarily in white matter fibers connected to sensory
      cortex. These findings suggest that the motor impairment in periventricular
      leukomalacia may, in part, reflect disruption of sensory connections outside
      classic pyramidal motor pathways.

PMID- 12221172
TI  - Genetic association of alpha2-macroglobulin polymorphisms with AD in southern
      Italy.
AB  - The authors investigated the segregation of two polymorphisms of the alpha2
      macroglobulin gene (A2M-I/D and A2M-Ile1000Val) in patients with sporadic AD from
      southern Italy. The A2M-I and A2M-Val1000 alleles were more frequent in cases
      than in controls, and this effect was independent from the APOE-epsilon4 status
      as well as from the age at onset of AD. Moreover, subjects carrying the A2M
      genotype I/I-Val/Val had a threefold increase of risk for AD. These data support
      a population-based susceptibility for AD linked to A2M polymorphisms.

PMID- 12221173
TI  - Gliomas presenting after age 10 in individuals with neurofibromatosis type 1
      (NF1).
AB  - Children with neurofibromatosis 1 (NF1) often develop low-grade gliomas, but
      brain tumors are infrequently encountered in adults with NF1. The authors present
      evidence from two clinical series, one including patients known to have NF1 and
      another focusing on adults with new onset brain tumors, that suggests an
      association between NF1 and symptomatic gliomas in older individuals. They also
      summarize the clinical data on 17 adolescents or adults with NF1 and symptomatic
      gliomas. The findings suggest that individuals with NF1 are at increased risk of
      developing gliomas throughout their lives.

PMID- 12221174
TI  - Is a "vanishing tumor" always a lymphoma?
AB  - The authors report clinical and radiologic characteristics and ultimate diagnosis
      in 12 patients with a regressing cerebral mass lesion. Primary CNS lymphoma
      (PCNL) was found in only half of the patients with such a lesion. In patients
      showing a complete resolution of the enhancing lesion the probability of finding
      a PCNL is smaller and survival is longer.

PMID- 12221175
TI  - P/Q type calcium-channel antibodies in paraneoplastic cerebellar degeneration
      with lung cancer.
AB  - Raised levels of P/Q type voltage-gated calcium-channel (VGCC) antibodies were
      found in 16 (41%) of 39 patients with paraneoplastic cerebellar degeneration
      (PCD) and Hu antibodies were found in nine (23%). Seven of the 16 VGCC antibody
      positive patients had Lambert-Eaton myasthenic syndrome (LEMS). Seven of 15 CSF
      samples had VGCC antibodies, with evidence of intrathecal synthesis in four. VGCC
      antibodies should be looked for in PCD, even if there are no symptoms of LEMS,
      and may be related to the cerebellar dysfunction.

PMID- 12221176
TI  - Corticosteroid- responsive asymmetric neuropathy with a myelin protein zero gene
      mutation.
AB  - A patient with hereditary neuropathy presented with asymmetric distal weakness.
      On nerve biopsy, there was demyelination and onion-bulb formation, and molecular
      analysis revealed that the patient was heterozygous for an MPZ mutation. The
      patient improved with corticosteroid treatment.

PMID- 12221177
TI  - Expression of X-linked bulbospinal muscular atrophy (Kennedy disease) in two
      homozygous women.
AB  - The authors describe the novel occurrence of homozygosity for the CAG expansion
      in the androgen receptor gene causing Kennedy disease in two sisters (ages 34 and
      42). Symptoms were limited to occasional muscle cramps and twitches. Physical
      examinations were normal apart from mild hand tremor in both women and rare
      perioral fasciculations in the older sibling. Electrodiagnostic studies were
      normal except for evidence of mild motor axonal loss in the sternocleidomastoid
      muscle of the older sibling.

PMID- 12221178
TI  - Premorbid weight, body mass, and varsity athletics in ALS.
AB  - Several famous athletes have been affected by ALS, and some epidemiologic studies
      have indicated that vigorous physical activity (heavy labor or athletics) is a
      risk factor for the disease. In a case-control study of 279 patients with motor
      neuron diseases and 152 with other neurologic diseases, the authors found that
      subjects with motor neuron diseases were more likely than controls to report they
      had always been slim or they had been varsity athletes. For slimness, the odds
      ratio (OR) was 2.21; 95% CI, 1.40 to 3.47. For varsity athletics, the OR was
      1.70; CI, 1.04 to 2.76.

PMID- 12221179
TI  - Pain and the body schema: effects of pain severity on mental representations of
      movement.
AB  - Previous research suggests that response times for imagined movements provide a
      sensitive measure of the integrity of the motor system. In a group of 12 patients
      with chronic unilateral arm pain, the authors demonstrate that response times for
      imagined movements are influenced by the severity of pain. Simulated large
      amplitude arm movements were slower for the painful as compared with the
      unaffected arms before, but not after, effective music therapy entrainment,
      suggesting that mental representations of movement are influenced by the current
      state of nociceptive feedback.

PMID- 12221180
TI  - Central neuropathic itch: a new treatment option?

PMID- 12221181
TI  - Transient global amnesia after sildenafil (Viagra) use.

PMID- 12221182
TI  - Adverse effects of phenytoin given for late-onset seizures in adults with Down
      syndrome.

PMID- 12221183
TI  - Evidence of somatic mosaicism in Sturge-Weber syndrome.

PMID- 12221184
TI  - Copper genes are not implicated in the pathogenesis of focal dystonia.

PMID- 12221185
TI  - Pure sensory stroke from cortical infarction.

PMID- 12221186
TI  - Personal history. One in a million?

PMID- 12221187
TI  - Comparison of rizatriptan and other triptans on stringent measures of efficacy.

PMID- 12221188
TI  - Spontaneous intracranial hypotension causing reversible frontotemporal dementia.

PMID- 12221189
TI  - Cholesterol and neuropathologic markers of AD: a population-based autopsy study.

PMID- 12221190
TI  - Will neurology residents with large student loan debts become academicians?

PMID- 12221191
TI  - The cerebellum may be directly involved in cognitive functions.

PMID- 12221192
TI  - Multiple sclerosis distribution in northern Sardinia: spatial cluster analysis of
      prevalence.

PMID- 12221193
TI  - Tongue involvement in amyloidoses.

PMID- 12221194
TI  - Depression is a treatable cause of suffering among multiple sclerosis patients
      and can result in suicide.

PMID- 12221195
TI  - Physiology of gastric enterochromaffin-like cells.
AB  - Enterochromaffin-like (ECL) cells are neuroendocrine cells in the gastric mucosa
      that control acid secretion by releasing histamine as a paracrine stimulant. The
      antral hormone gastrin and the neural messenger pituitary adenylyl cyclase
      activating peptide (PACAP) potently stimulate histamine synthesis, storage, and
      secretion by ECL cells. Histamine is stored in secretory vesicles via V-type
      ATPases and vesicular monoamine transporters of subtype 2 (VMAT-2). Plasmalemmal
      calcium entry occurs via L-type calcium channels upon stimulation with
      secretagogues. K(+) and Cl(-) channels maintain the membrane potential. Calcium
      triggered exocytosis of histamine is mediated by interacting SNARE proteins,
      especially by synaptobrevin and SNAP-25. Dynamins and amphiphysins appear to play
      a key role in endocytosis. ECL cells are under transcriptional control of various
      hormones. Gastrin stimulates transcriptional activity of the histidine
      decarboxylase (HDC), VMAT-2, and chromogranin A promoter by activation of Sp1
      elements and CREB. During chronic Helicobacter pylori infection, pro-inflammatory
      cytokines are released that can also affect ECL cells, thus impairing their
      secretory function and viability, which can predispose to hypochlorhydria and
      gastric carcinogenesis.

PMID- 12221196
TI  - Editorial announcement.

PMID- 12221197
TI  - Metabolomics and individual metabolic assessment: the next great challenge for
      nutrition.

PMID- 12221198
TI  - The influence of different fats and fatty acids on obesity, insulin resistance
      and inflammation.
AB  - Dietary fat and its relation to obesity has been a controversial issue for
      several years. In this review, several kinds of data relating to this issue are
      presented. There are epidemiological cross-country data and data within countries
      showing an effect. However, in the United States, the intake of fat appears to be
      declining, whereas the prevalence of obesity rises-the American Paradox. Clinical
      studies show that trans fatty acids can increase insulin resistance and that
      exercise can enhance the rate of adaptation to a high fat diet by increasing the
      rate of fat oxidation. The differences in response of inflammatory signals and of
      insulin resistance to different fatty acids indicate that not all fatty acids are
      the same. There are also experimental data showing that most, but not all,
      animals consuming a high fat diet will become obese. A number of mechanisms have
      been postulated for this difference, including differential sensitivities to
      neurotransmitters, to the intestinal peptide, enterostatin, and to individual
      fatty acids. One important conclusion from this review is that both total fat and
      individual fatty acids have to be considered when reaching conclusions about
      dietary fat and obesity.

PMID- 12221199
TI  - A physiological basis for disparities in diabetes and heart disease risk among
      racial and ethnic groups.

PMID- 12221200
TI  - Effects on the human serum lipoprotein profile of beta-glucan, soy protein and
      isoflavones, plant sterols and stanols, garlic and tocotrienols.
AB  - The effects of beta-glucan, soy protein, isoflavones, plant sterols and stanols,
      garlic and tocotrienols on serum lipoproteins have been of great interest the
      last decade. From a critical review of the literature, it appeared that recent
      studies found positive as well as no effects of beta-glucan from oats on serum
      LDL cholesterol concentrations. These conflicting results may suggest that the
      cholesterol-lowering activity of products rich in oat beta-glucan depends on
      factors, such as its viscosity in the gastrointestinal tract, the food matrix
      and/or food processing. The effects of beta-glucan from barley or yeast on the
      lipoprotein profile are promising, but more human trials are needed to further
      substantiate these effects. It is still not clear whether the claimed
      hypocholesterolemic effects of soy can be attributed solely to the isoflavones.
      Several studies found no changes in serum LDL cholesterol concentrations after
      consumption of isolated soy isoflavones (without soy protein), indicating that a
      combination of soy protein and isoflavones may be needed for eliciting a
      cholesterol-lowering effect of soy. Therefore, the exact (combination of) active
      ingredients in soy products need to be identified. The daily consumption of 2-3 g
      of plant sterols or stanols reduces LDL cholesterol concentrations by 9-14%. It
      has been demonstrated that functional foods enriched with plant sterols and
      stanols are effective in various population groups, and in combination with
      cholesterol-lowering diets or drugs. Whether garlic or garlic preparations can be
      used as a lipid-lowering agent is still uncertain. It is important to
      characterize the active components in garlic and their bioavailability after
      ingestion. It is not very likely that tocotrienols from palm oil or rice bran oil
      have favorable effects on the human serum lipoprotein profile.

PMID- 12221201
TI  - Dietary fish oil increases acetylcholine- and eicosanoid-induced contractility of
      isolated rat ileum.
AB  - The long-chain (n-3) polyunsaturated fatty acids (PUFA) have been reported to
      exhibit health benefits and healing properties for the gastrointestinal tract.
      The aim of this study was to investigate the effects of dietary fish oil
      supplementation on the in vitro contractility of gut tissue. Rats (9 wk old) were
      fed synthetic diets supplemented with 170 g/kg Sunola oil (SO; 850 g/kg as oleic
      acid [18:1(n-9)]) or with 100 g/kg of the SO replaced by saturated animal fat
      (SF) or fish oil (FO) for 4 wk. In the colon, there was no difference in the
      sensitivity (50% effective concentration) or the maximal contraction among the
      three dietary groups induced by acetylcholine or 8-iso-prostaglandin (PG)E(2)
      with the rat colon being relatively insensitive to the thromboxane mimetic U
      46619. However, in the ileum, the FO group had greater maximal contractions
      induced by acetylcholine and 8-iso-PGE(2) compared with the SO and SF groups (P <
      0.05), and greater maximal contractions induced by PGE(2), PGF(2alpha) and U
      46619 compared with the SF group (P < 0.05). FO feeding increased the
      incorporation of (n-3) PUFA (eicosapentaenoic [20:5(n-3)], docosapentaenoic
      [22:5(n-3)] and docosahexaenoic acids [22:6(n-3) primarily at the expense of (n
      6) PUFA (linoleic [18:2(n-6)] and arachidonic acids [20:4(n-6)]) in the ileum and
      colon phospholipid fatty acids (P < 0.05). The FO group had a lower cecal digesta
      pH (P < 0.001) and a greater butyrate concentration than the SF group (P < 0.05).
      These results suggest that dietary (n-3) PUFA may modulate the contractility of
      the small intestine.

PMID- 12221202
TI  - The carbonyl content of specific plasma proteins is decreased by dietary copper
      deficiency in rats.
AB  - Copper (Cu) deficiency is associated with increased susceptibility of tissue
      homogenates or lipoproteins to oxidation in vitro. Plasma is easily sampled and
      contains both lipid and protein components that may be susceptible to oxidation,
      making it appropriate to investigate plasma oxidation variables as biomarkers of
      in vivo oxidative stress. Oxidation of plasma proteins may be discernible as an
      increased content of carbonyl (aldehyde or ketone) groups on the proteins.
      Weanling male Long-Evans rats were fed sucrose-based modified AIN-93G diets with
      (+Cu, 6.2 mg Cu/kg diet) or without (-Cu, 0.4 mg/kg) added Cu for 4 wk before
      killing. Plasma and RBC Cu,Zn-superoxide dismutase activities and liver Cu
      concentration were significantly decreased and relative heart weight was
      significantly increased, confirming the Cu-deficient status of the -Cu rats.
      Dinitrophenylhydrazine (DNP) derivatization followed by SDS-PAGE and Western
      blotting using commercial anti-DNP antibody demonstrated that several plasma
      proteins in +Cu control rats showed evidence of carbonyl groups. The carbonyl
      content of these bands was lower in -Cu rats, not greater as would have been
      expected with oxidative damage to these proteins. Although dietary Cu deficiency
      may increase susceptibility to oxidative stress, it does not lead to accumulation
      of oxidized plasma proteins in this animal model.

PMID- 12221203
TI  - The hypocholesterolemic effect of high amylose cornstarch in rats is mediated by
      an enlarged bile acid pool and increased fecal bile acid excretion, not by cecal
      fermented products.
AB  - Sham-operated and cecectomized rats were fed for 21 d a cholesterol-free purified
      diet containing (200 g/kg) either normal cornstarch (CS) or high amylose
      cornstarch (HACS). In both types of rats, those fed the HACS diet had a
      significantly lower plasma total cholesterol concentration and a significantly
      larger intestinal bile acid pool than those fed the CS diet. In cecectomized
      rats, those fed the HACS diet had significantly lower plasma HDL and LDL
      cholesterol concentrations, a significantly greater fecal bile acid excretion and
      a significantly lower hepatic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase
      mRNA concentration than those fed the CS diet. The plasma triglyceride
      concentration and LDL-receptor mRNA concentration were not affected by the diet
      or cecectomy. In sham-operated rats, the propionate concentration in the cecal
      contents was significantly greater in those fed the HACS diet than in those fed
      the CS diet. Compared with sham-operated rats, cecectomized rats had
      significantly enhanced cholesterol 7alpha-hydroxylase activity. In intact rats,
      biliary bile acid flux into the small intestine was significantly greater in
      those fed the HACS diet than in those fed the CS diet. Thus, the
      hypocholesterolemic effect of HACS appears to be mediated by accelerated fecal
      excretion of bile acids and increases in the intestinal pool and biliary flux of
      bile acids, and not by cecal fermentation products.

PMID- 12221204
TI  - Moderate iron overload enhances lipid peroxidation in livers of rats, but does
      not affect NF-kappaB activation induced by the peroxisome proliferator, Wy
      14,643.
AB  - It has been hypothesized that high concentrations of tissue iron may enhance
      carcinogenesis induced by free radical mechanisms. Wy-14,643 is a peroxisome
      proliferator that is hepatocarcinogenic in rats. Tumor induction may result in
      part from excessive production of reactive oxygen species, particularly H(2)O(2).
      The purpose of this study was to examine the effect of iron status on oxidative
      stress and NF-kappaB activation in livers of rats treated with Wy-14,643. Forty
      eight male Sprague-Dawley rats were fed one of four diets (20, 45, 650, 1500 mg
      Fe/kg diet) for 28 d. At the time of tissue collection, liver iron ranged from
      1.4 to 9.9 micro mol/g wet tissue in the diet groups. Wy-14,643 (0 or 0.1 g/100 g
      diet) was added to the diet for the final 10 d of the study. Wy-14,643 doubled
      the liver weight/body weight ratio (P = 0.0001), which was also increased by iron
      supplementation (P < 0.01). Iron supplementation increased thiobarbituric acid
      reactive substances and/or conjugated dienes, but there was no synergism between
      Wy 14,643 and iron on lipid peroxidation measures. The hepatic DNA binding
      activity of NF-kappaB was increased in rats administered Wy-14,643. However,
      differences in liver iron concentration did not alter activation of NF-kappaB in
      untreated rats or in those treated with Wy-14,643. DNA double-strand breakage was
      not affected by iron or Wy-14,643. In summary, although moderate changes in iron
      status altered liver lipid peroxidation, iron did not significantly increase
      oxidative stress induced by a hepatocarcinogenic peroxisome proliferator.

PMID- 12221205
TI  - Lipoprotein oxidation mediated by J774 murine macrophages is inhibited by
      individual red wine polyphenols but not by ethanol.
AB  - The in vitro capacities of individual polyphenols in red wine to inhibit the cell
      mediated oxidation of lipoproteins and their effects on cell viability were
      determined. LDL and HDL were incubated with J774.A1 macrophages and 2 and 4 micro
      mol/L copper, respectively, in the absence and presence of polyphenols in ethanol
      at concentrations found in red wine. A mixture of polyphenols in amounts found in
      red wine equivalent to 0.2 g/L ethanol and 0.05 g/L ethanol inhibited
      thiobarbituric acid-reactive substance production from LDL by 91.7 and 45.9%,
      respectively, compared with ethanol controls (P < 0.01). HDL oxidation was
      inhibited 85 and 82.4% by the polyphenols at 0.2 and 0.05 g/L ethanol (P < 0.01).
      The effects of the polyphenol mixture on LDL oxidation were confirmed by
      measuring production of conjugated dienes and lipid peroxides, and
      trinitrobenzene sulfonic acid reactivity. Catechin at the concentration found in
      red wine (1.32 micro mol/L) at an ethanol concentration equivalent to 0.2 g/L
      inhibited LDL oxidation by 83.2%, while epicatechin (0.56 micro mol/L) and gallic
      acid (1.02 micro mol/L) inhibited by 60.6 and 26.9%, respectively (P < 0.05). At
      1 micro mol/L, LDL oxidation was inhibited by epicatechin, catechin and quercetin
      by 86.2, 79.9 and 69.4%, respectively (P < 0.05). Incubation of macrophages with
      ethanol alone and with polyphenols in ethanol did not affect cell viability. Our
      results indicate that catechin and epicatechin are the major contributors to the
      antioxidant activity of red wine.

PMID- 12221206
TI  - Hepatic cytochrome p450-2A and phosphoribosylpyrophosphate synthetase-associated
      protein mRNA are induced in gerbils after consumption of isoflavone-containing
      protein.
AB  - Soy intake reduces cholesterol levels, but neither the exact component in soy
      causing this reduction nor the mechanism by which cholesterol is reduced is known
      with certainty. In this study, a genetic screen was performed to identify hepatic
      mRNA in gerbils regulated by soy or soy isoflavones. Gerbils were fed casein, an
      alcohol-washed soy-based diet (containing low levels of isoflavones), and the soy
      based diet supplemented with an isoflavone-containing soy extract. After feeding
      for 28 d, gerbils were killed, hepatic RNA was isolated, and genes that were
      differentially expressed in any of the three dietary conditions were identified.
      Fifteen different mRNA were originally selected, including two mRNA that were
      studied further and shown to be highly regulated. Messenger RNA levels for both
      cytochrome P450-2A and phosphoribosylpyrophosphate synthetase-associated protein
      were up-regulated in a dose-dependent manner when soy replaced casein in the diet
      at 0, 33, 67 and 100% of original casein levels. A subsequent experiment used
      purified amino acid mixtures resembling the percentage amino acid composition of
      soy and casein to ensure that isoflavone-free protein sources could be tested.
      Using these mixtures, a 2 x 2 x 2 design tested: natural vs. synthetic protein
      sources, casein- vs. soy-based diets, and isoflavone extract-supplemented or
      supplement-free diets. This design demonstrated that these two mRNA were again
      significantly up-regulated more than twofold (P < 0.05) in gerbils fed all diets
      containing isoflavones. Induction of these two mRNA by soy may be due to the aryl
      hydrocarbon receptor element in the promoter region of both genes.

PMID- 12221207
TI  - Hepatic glycine N-methyltransferase is up-regulated by excess dietary methionine
      in rats.
AB  - Glycine N-methyltransferase (GNMT) regulates S-adenosylmethionine (SAM) levels
      and the ratio of SAM:S-adenosylhomocysteine (SAH). In liver, methionine
      availability, both from the diet and via the folate-dependent one-carbon pool,
      modulates GNMT activity to maintain an optimal SAM:SAH ratio. The regulation of
      GNMT activity is accomplished via posttranslational and allosteric mechanisms. We
      more closely examined GNMT regulation in various tissues as a function of excess
      dietary methyl groups. Sprague Dawley rats were fed either a control diet (10%
      casein plus 0.3% L-methionine) or the control diet supplemented with graded
      levels (0.5-2%) of L-methionine. Pair-fed control groups of rats were included
      due to the toxicity associated with high methionine consumption. As expected, the
      hepatic activity of GNMT was significantly elevated in a dose-dependent fashion
      after 10 d of feeding the diets containing excess methionine. Moreover, the
      abundance of hepatic GNMT protein was similarly increased. The kidney had a
      significant increase in GNMT as a function of dietary methionine, but to a much
      lesser extent than in the liver. For pancreatic tissue, neither the activity of
      GNMT nor the abundance of the protein was responsive to excess dietary
      methionine. These data suggest that additional mechanisms contribute to
      regulation of GNMT such that synthesis of the protein is greater than its
      degradation. In addition, methionine-induced regulation of GNMT is dose dependent
      and appears to be tissue specific, the latter suggesting that the role it plays
      in the kidney and pancreas may in part differ from its hepatic function.

PMID- 12221208
TI  - Weaning affects the expression of heat shock proteins in different regions of the
      gastrointestinal tract of piglets.
AB  - Heat shock proteins (HSP) play a central role in the protection of cells, tissues
      or organs subjected to various types of stressors. Different nutrients have been
      recently shown to exert their protection through the induction of HSP. Because
      these nutrients alleviate alterations of the intestine after weaning in pigs,
      this study was designed to obtain basic information on the expression of HSP 27,
      heat shock cognate 70 (HSC 70), HSP 70 and HSP 90 along the gastrointestinal
      tract (GIT) of young pigs and to study the effect of weaning on this expression.
      Pigs were weaned at 28 or 21 d and slaughtered at various times postweaning. All
      HSP were expressed in the GIT segments studied before and after weaning. However,
      the expression of HSP 27 and HSP 70 was transiently increased in the stomach and
      duodenum between 6 and 12 h postweaning and between 24 and 48 h in the mid
      jejunum, ileum and colon. Their expressions were transiently decreased in the
      ileum. Expression of HSP 90 increased in the stomach and jejunum but decreased in
      the duodenum, ileum and colon. Similar results were obtained at both ages of
      weaning. We conclude that the HSP studied are present all along the gut of pigs
      and that their expression is modulated through weaning according to spatial
      temporal patterns. The modulation by nutrients of HSP and their protective role
      on the GIT remain to be investigated in pigs.

PMID- 12221209
TI  - A soy protein diet alters hepatic lipid metabolism gene expression and reduces
      serum lipids and renal fibrogenic cytokines in rats with chronic nephrotic
      syndrome.
AB  - Nephrotic syndrome (NS) is characterized by the presence of proteinuria and
      hyperlipidemia. However, ingestion of soy protein has a hypolipidemic effect. The
      present study was designed to determine whether the ingestion of a 20% soy
      protein diet regulates the expression of hepatic sterol regulatory element
      binding protein (SREBP)-1, fatty acid synthase (FAS), malic enzyme, beta-hydroxy
      beta-methylglutaryl-CoA (HMG-CoA) reductase (r) and synthase (s), and LDL
      receptor (r), and to assess whether soy protein improves lipid and renal
      abnormalities in rats with chronic NS. Male Wistar rats were injected with
      vehicle or with puromycin aminonucleoside to induce NS and were fed either 20%
      casein or soy protein diets for 64 d. NS rats fed 20% soy protein had improved
      creatinine clearance and reduced proteinuria, hypercholesterolemia,
      hypertriglyceridemia, as well as VLDL-triglycerides and LDL cholesterol compared
      with NS rats fed the 20% casein diet. In addition, the soy protein diet decreased
      the incidence of glomerular sclerosis, and proinflammatory cytokines in kidney.
      Ingestion of the soy protein diet by control rats reduced the gene expression of
      SREBP-1, malic enzyme, FAS and increased HMG-CoAr, HMG-CoAs and LDLr. However, NS
      rats fed either casein or soy protein diets had low insulin concentrations with
      reductions in SREBP-1, FAS and malic enzyme expression compared with control rats
      fed the casein diet. NS rats fed the soy diet also had lower HMG-CoAr and LDLr
      mRNA levels than NS rats fed casein. In conclusion, the beneficial effects of soy
      protein on lipid metabolism are modulated in part by SREBP-1. However, in NS
      rats, the benefit may be through a direct effect of this protein on kidney rather
      than mediated by changes in expression of hepatic lipid metabolism genes.

PMID- 12221210
TI  - Acute enteral glutamine infusion enhances heme oxygenase-1 expression in human
      duodenal mucosa.
AB  - The heat shock protein, heme oxygenase-1 (HO-1), contributes to the protection of
      the intestine. Some experimental models suggest that induction of HO-1 by
      glutamine may contribute to the preservation of intestinal mucosa. The effect of
      an enteral infusion of glutamine for 6 h on HO-1 expression in duodenal mucosa
      was studied in healthy men and women and compared with an isonitrogenous mixture
      of amino acids. After enteral infusion, endoscopic duodenal biopsies were
      performed and either fixed in formalin for immunohistochemistry or frozen for HO
      1 mRNA analysis by reverse transcriptase-polymerase chain reaction. Histologic
      examination revealed that HO-1 was constitutively expressed in intestinal
      epithelial cells (IEC), and that glutamine increased the grade of HO-1
      immunostaining (P </= 0.01). Glutamine also increased the percentage of HO-1
      immunoreactive lamina propria cells (LPC, 10.5 vs. 7.5%, P </= 0.05). Glutamine
      significantly increased HO-1 mRNA expression compared with control amino acids:
      median (range) 156 (102-182) vs. 100 (68-179)%, P </= 0.05. The mRNA level for HO
      1 was correlated with the percentage of immunoreactive LPC (r = 0.55, P = 0.017)
      and the grade of immunostaining in IEC (r = 0.51, P = 0.030). In conclusion,
      glutamine enhanced HO-1 mRNA and protein expression in human duodenal mucosa.
      These data support further evaluation of the effects of glutamine on intestinal
      HO-1 during states of intestinal inflammation.

PMID- 12221211
TI  - Postprandial hyperglycemia and insulin sensitivity differ among lean young adults
      of different ethnicities.
AB  - Both postprandial hyperglycemia and insulin resistance (IR) have implications for
      the development of cardiovascular disease. The present study was designed to
      examine differences in postprandial glycemia and insulin sensitivity among young
      adults of different ethnic origins. Lean, healthy subjects (n = 60) from five
      ethnic groups [20 European Caucasians, 10 Chinese, 10 South East (SE) Asians, 10
      Asian Indians and 10 Arabic Caucasians] were matched for age, body mass index,
      waist circumference, birth weight and current diet. A 75-g white bread
      carbohydrate challenge was fed to assess postprandial glycemia and insulinemia.
      Insulin sensitivity was assessed in three groups by the euglycemic
      hyperinsulinemic clamp and in all subjects by homeostasis model assessment (HOMA)
      modeling. Postprandial hyperglycemia (incremental area under the curve) and
      insulin sensitivity (M-value) both showed a twofold variation among the groups (P
      < 0.001) and were significantly related to each other (R(2) = 56%, P < 0.001).
      Young SE Asians had the highest postprandial glycemia and lowest insulin
      sensitivity, whereas European and Arabic Caucasian subjects were the most insulin
      sensitive and carbohydrate tolerant. These findings suggest that IR is evident
      even in lean, young adults of some ethnic groups and is associated with
      significant increases in postprandial glycemia and insulinemia in response to a
      realistic carbohydrate load.

PMID- 12221212
TI  - Glutamine-enriched enteral nutrition increases HLA-DR expression on monocytes of
      trauma patients.
AB  - The aim of this study was to investigate the effect of glutamine-(Gln)-enriched
      enteral nutrition (EN) on human leukocyte antigen (HLA)-DR and FcgammaR1/CD64
      expression on monocytes and plasma glutamine concentrations in multi-trauma
      patients. HLA-DR expression on monocytes is crucial in the presentation of
      foreign antigen to the immune system and is severely reduced in trauma patients.
      In vitro monocyte HLA-DR and FcgammaRI/CD64 expression is dependent on glutamine
      availability. To study the effect of glutamine supplemented enteral nutrition on
      HLA-DR and FcgammaRI/CD64 expression on CD14(+) monocytes, 55 multi-trauma
      patients were studied in a randomized, double-blinded, controlled trial. Trauma
      patients received either a Gln-enriched EN (glutamine group, n = 28) or an
      isocaloric, isonitrogenous control EN (control group, n = 27) and were compared
      with a group of age-matched healthy volunteers (healthy volunteers, n = 53). On d
      1, 5, 9 and 14 after trauma, expressions of HLA-DR and FcgammaRI/CD64 were
      determined on CD14(+) monocytes using FACS analysis. Plasma glutamine levels were
      measured using HPLC. Plasma glutamine was lower in both trauma patient groups
      compared with healthy volunteers and from d 3 to d 5; glutamine was higher in the
      glutamine group than in the control group. On d 1, HLA-DR expression was much
      lower in both trauma patient groups than in healthy volunteers. HLA-DR expression
      was greater on d 5, 9 and 14 in the glutamine group than in the control group.
      FcgammaRI/CD64 expression on monocytes of trauma patients was not different than
      the expression of healthy volunteers. This study showed that glutamine-enriched
      enteral nutrition was associated with a higher HLA-DR expression on CD14(+)
      monocytes of trauma patients. No difference in monocyte FcgammaRI/CD64 expression
      was detected between patients that received the two enteral diets and between
      trauma patients and the healthy volunteers. Increased HLA-DR expression may
      improve cellular immune function and may be involved in the beneficial effect of
      glutamine on the occurrence of infections in trauma patients.

PMID- 12221213
TI  - Hydrolysis of isoflavone glycosides to aglycones by beta-glycosidase does not
      alter plasma and urine isoflavone pharmacokinetics in postmenopausal women.
AB  - We investigated whether the bioavailability of isoflavones could be enhanced by
      enzymatic hydrolysis of glycosides to aglycones before consumption of a
      nonfermented soy food. Two drinks were formulated with an enriched isoflavone
      extract from soy germ (Fujiflavone P10), one of which was hydrolyzed
      enzymatically with beta-glucosidase to produce aglycones. In a randomized, double
      blinded, cross-over study, six European, postmenopausal women consumed each soy
      drink at a 1-wk interval at a concentration of 1 mg total isoflavones/kg body.
      The plasma and urinary pharmacokinetics of daidzein, genistein and glycitein did
      not differ after consumption of the two beverages. Plasma total isoflavone
      concentrations reached 4-5 micro mol/L. The pharmacokinetics of glycitein were
      similar to those of daidzein. The isoflavone secondary metabolites detected were
      dihydrodaidzein in plasma and O-desmethylangolensin, equol, and dihydrogenistein
      in urine. The ratios of individual isoflavones to one another were not conserved
      from food to plasma to urine, indicating that the individual isoflavones do not
      have the same absorptions and body retentions. In conclusion, previous hydrolysis
      of glycosides to aglycones does not enhance the bioavailability of isoflavones in
      humans.

PMID- 12221215
TI  - Orally ingested human lactoferrin is digested and secreted in the upper
      gastrointestinal tract in vivo in women with ileostomies.
AB  - Lactoferrin (LF), a glycoprotein present in milk and other secretions, may
      provide a nutritional ingredient for the treatment of intestinal disorders
      associated with hyperpermeability, oxidative stress and inflammation. The aim of
      the study was to determine the survival rate of orally administered recombinant
      human lactoferrin (rhLF) in the upper gastrointestinal (GI) tract and in the
      small intestine in vivo in humans. Female ileostomy patients [n = 8; median age
      44 (43-57) y] ingested a test beverage containing 5 g rhLF and collected full
      ileostomy output for 24 h. The passage of the test beverage was monitored using
      radio-opaque markers. Intact LF in ileal effluent was quantified by ELISA. The
      entire test beverage passed the small bowel during the 24-h ileal effluent
      collection period. LF was excreted at a low but constant rate [0.35 (0.28-0.47)
      micro g LF/2 h]. Gastrointestinal passage of the test beverage and LF excretion
      over time in the ileal effluent were not correlated. In total, a median of 4
      micro g LF was excreted over the 24-h collection period, whereas 5 g rhLF was
      ingested. Hence, dietary rhLF is digested in the upper GI tract and does not
      reach the colon. Intact LF appearing in ileostomy effluent is likely to originate
      from an endogenous source.

PMID- 12221214
TI  - Carbohydrate digestion in humans from a beta-glucan-enriched barley is reduced.
AB  - Obese and diabetic patients may benefit from foodstuffs that are poorly absorbed
      and/or digested at a slower rate. Prowashonupana (PW) is a cultivar of barley,
      whose grains are enriched in beta-glucans, and thus may be less digestible than
      standard barley (barley cultivar (BZ) 594.35.e). To test this, both kinds of
      barley were grown in a chamber into which (13)CO(2) was injected. On two
      occasions, 10 healthy hydrogen (H(2))-producing adults consumed in random order
      one 35-g portion of each of the cooked, dehulled (13)C-enriched grains. CO(2)
      production was measured in a whole-body direct calorimeter, and H(2) and
      (13)CO(2) were measured in breath at baseline and intermittently for 450 min. The
      percentage of the (13)C dose recovered in breath was calculated. Results were
      compared by repeated measures analysis of variance (ANOVA). The percentage of the
      (13)C dose oxidized was greater after BZ than after PW consumption (P < 0.05).
      The area under the curve for H(2) was greater after PW (mean +/- SD, 8658 +/-
      6582) than after BZ (5178 +/- 4759) intake (P < 0.05), whereas there was no
      difference in CO(2) production. We conclude that absorption of PW is
      significantly lower than that of BZ, making the modified barley appropriate for
      obese and diabetic patients.

PMID- 12221216
TI  - Fructose prefeeding reduces the glycemic response to a high-glycemic index,
      starchy food in humans.
AB  - The study objective was to determine whether a small dose of fructose
      administered before or simultaneously with a high glycemic index, starchy food
      decreases postprandial glycemic response. Nondiabetic healthy adults (n = 31;
      mean +/- SEM: age, 26 +/- 1 y; weight, 66.1 +/- 2.6 kg; body mass index, 23.3 +/-
      0.6 kg/m(2)) were studied in a randomized crossover design. Treatments consisted
      of 50 g available carbohydrate from instant mashed potatoes fed alone (control)
      or with 10 g fructose fed 60, 30 or 0 min before the potato meal. Capillary
      finger-stick blood samples were analyzed for glucose concentration at -60, -30,
      0, 15, 30, 45, 60, 90 and 120 min relative to the ingestion of the potato meal.
      Compared with the control, the positive incremental area under the glucose curve
      was reduced 25 and 27% (P < 0.01) when fructose was fed either 60 or 30 min
      before the meal, respectively. In contrast to previous studies demonstrating that
      immediate administration of a small amount of fructose lowers the glycemic
      response to a glucose solution, we found that fructose must be consumed before a
      starchy food to reduce postprandial glycemia.

PMID- 12221218
TI  - Phylloquinone absorption from phylloquinone-fortified oil is greater than from a
      vegetable in younger and older men and women.
AB  - Studies that have compared the absorption of phylloquinone from green vegetables
      and oils have equivocal results. To address differences in approaches used to
      assess absorption of phylloquinone, a 24-h absorption study was conducted in 18
      younger (20-40 y) and 18 older (60-80 y) men and women as part of a larger
      metabolic study that compared changes in vitamin K status in response to broccoli
      and phylloquinone-fortified oil (377 +/- 46 and 417 +/- 45 micro g/d,
      respectively). Absorption was defined as the 24-h area under the curve (AUC) for
      plasma phylloquinone concentrations (both unadjusted and adjusted for
      triglyceride concentrations). The mean AUC for plasma phylloquinone
      concentrations (both unadjusted and adjusted) were significantly greater after
      consumption of the phylloquinone-fortified oil diet compared with the broccoli
      diet (P < 0.001). However, there were no differences between the two treatments
      in 24-h fasting plasma phylloquinone concentrations. Although there were no age
      differences in the AUC for plasma phylloquinone adjusted for triglycerides, older
      adults had significantly higher plasma phylloquinone concentrations (both
      unadjusted and adjusted) at 0 and 24 h than the younger adults (P < 0.001). These
      data emphasize that the use of different approaches for the assessment of vitamin
      K absorption can result in disparate conclusions.

PMID- 12221217
TI  - Soy protein supplementation increases serum insulin-like growth factor-I in young
      and old men but does not affect markers of bone metabolism.
AB  - Recent studies suggest that soy protein (SP) protects bone in women; however, its
      effects on bone metabolism in men have not been investigated. Healthy men (59.2
      +/- 17.6 y) were assigned to consume 40 g of either SP or milk-based protein (MP)
      daily for 3 mo in a double-blind, randomized, controlled, parallel design. Serum
      insulin-like growth factor-I (IGF-I), which is associated with higher rates of
      bone formation, was greater (P < 0.01) in men supplemented with SP than in those
      consuming MP. Serum alkaline phosphatase and bone-specific alkaline phosphatase
      activities, markers of bone formation, and urinary deoxypyridinoline excretion, a
      specific marker of bone resorption, were not different between the SP and MP
      groups. Furthermore, because substantial reductions in bone density occur in men
      at approximately 65 y of age, data were analyzed separately for men >/=65 y and
      those <65 y of age. The response to protein supplementation was consistent in the
      two age groups. The effects of SP on serum IGF-I levels suggest that SP may
      positively influence bone in men. Longer-duration studies examining the effects
      of SP or its isoflavones on bone turnover and bone mineral density and content in
      men are warranted.

PMID- 12221219
TI  - Consumption of the folate breakdown product para-aminobenzoylglutamate
      contributes minimally to urinary folate catabolite excretion in humans:
      investigation using [(13)C(5)]para-aminobenzoylglutamate.
AB  - Folate catabolism represents the major route of folate turnover in humans and
      involves cleavage of the C9-N10 bond producing a pterin and para
      aminobenzoylglutamate (pABG). Thus, the quantitation of pABG and its acetylated
      more predominant counterpart para-acetamidobenzolyglutamate (apABG) may be useful
      in assessing folate status and requirements. However, until the in vivo fate of
      dietary pABG is understood, studies using pABG excretion parameters can not be
      fully interpreted. As part of a larger study, an oral dose (376 nmol or 100 micro
      g) of [(13)C(5)]pABG in 40 mL apple juice was ingested by pregnant women (2nd
      trimester, n = 2) and nonpregnant controls (n = 2) consuming controlled total
      folate intakes of 450 or 850 micro g/d. Urine collections (24 h) were obtained
      over the next 4 d and gas chromatography-mass spectrometry was used to measure
      urinary [(13)C(5)]pABG, [(13)C(5)]apABG and [(13)C(5)]folate. Of the 376 nmol
      [(13)C(5)]pABG administered, only 17.5 +/- 6.4 nmol; mean +/- SEM) or 4.6 +/-
      1.7% of the dose was accounted for in the urine. Most of the excreted
      [(13)C(5)]pABG, in acetamido form (15.1 +/- 5.3 nmol), was excreted the day after
      the dose. No urinary [(13)C(5)]folate was detected. Folate intake did not seem to
      influence the urinary excretion of total pABG derived from oral pABG, whereas
      pregnancy may lessen total pABG excretion derived from oral pABG. Overall, these
      results suggest that the contribution of dietary pABG to the urinary excretion of
      pABG and apABG is small.

PMID- 12221220
TI  - Developmental trajectories of poorly nourished toddlers that received a
      micronutrient supplement with and without energy.
AB  - Experimental and quasi-experimental studies on the effects of nutritional
      supplements on development in young children generally include snapshots of
      development. Developmental outcomes are better revealed when multiple assessments
      are made over time. We compared the effects of a micronutrient intervention with
      and without supplementary energy on the mental and motor growth curves of poorly
      nourished toddlers in West Java. Subjects (12-mo-old cohort, n = 33; 18-mo-old
      cohort, n = 42) were randomly assigned to receive energy + micronutrients (E + M)
      or micronutrients (M) daily for 12 mo. The cohort/treatment groups were then
      classified as either relatively short or tall. Within the 12-mo cohort, the
      baseline mean length Z-scores ranged from -2.53 to -1.29 and the baseline mean
      weight Z-scores ranged from -3.05 to -2.18. The same pretreatment anthropometrics
      for the older cohort ranged from -3.22 to -1.59 and from -3.42 to -2.26. Mental
      and motor development scores (Bayley) were obtained at baseline and every 2 mo
      for 12 mo. There was a Cohort x Length Category x Supplement interaction for
      mental slopes (P < 0.01). Slopes for tall-E + M (b = 5.35) and tall-M children (b
      = 5.39) in the 18-mo cohort were equivalent, but slopes for short-E + M (b =
      6.13) and short-M (b = 4.67) children differed greatly (P = 0.03). On the basis
      of this finding and findings previously reported from this study, we concluded
      that the unfavorable developmental response to the M supplement that was
      restricted to the shortest children within an already disadvantaged group.

PMID- 12221221
TI  - Quantitative role of plasma free fatty acids in the supply of arachidonic acid to
      extrahepatic tissues in rats.
AB  - Local desaturation-elongation of linoleic acid, uptake of 2-arachidonyl
      lysophosphatidylcholine, and uptake plasma unesterified arachidonic acid (AA) are
      assumed to be the most important sources of AA for extrahepatic tissues. In this
      study, we investigated the clearance rate as well as the retention rate of plasma
      unesterified (14)C-AA in different tissues in fed rats. The initial half-life of
      (14)C-AA in rat plasma was 3.8 s, and the average pool size of rat plasma
      unesterified AA was 76 nmol. We calculated that 604 nmol of unesterified AA was
      cleared from the rat plasma per minute. The retention rate of AA per gram of
      tissue in the heart (13 nmol/min per g), lungs (12 nmol/min per g), kidney (8
      nmol/min per g) and bone marrow (6 nmol/min per g) was higher than that in other
      tissues but was lower than that in liver (23 nmol/min per g). The total uptake
      was highest in skeletal muscle (249 +/- 27 nmol/min), in liver (226 +/- 15
      nmol/min) and in bone marrow (39 +/- 3 nmol/min). More than 80% of retained (14)C
      AA was found in phospholipids in most tissues. The conclusion is that despite the
      low concentration plasma unesterified, AA is a major source of phospholipid AA in
      several extrahepatic tissues in rats, due to its rapid turnover and selective
      acylation into phospholipids.

PMID- 12221222
TI  - Moderate folate deficiency influences polyamine synthesis in rats.
AB  - Spermidine, spermine and putrescine are polyamines, essential growth factors in
      mammalian cells. Decarboxylated S-adenosylmethionine (SAM) is an essential
      precursor in the formation of both spermidine and spermine. SAM is formed from
      methionine through the addition of adenosine. Because 5-methyltetrahydrofolate
      donates a methyl group to homocysteine to produce methionine, folate deficiency
      may decrease polyamine synthesis. Weanling male Sprague-Dawley rats were fed an
      amino acid-defined diet with 2 mg folic acid/kg diet (control) or no added folic
      acid (test). Blood, liver, brain, jejunum, ileum and colon samples were collected
      at the end of 5 wk. Compared with controls, rats fed the test diet had a 72%
      reduction in plasma folate (123.6 +/- 13.1 vs. 34.6 +/- 2.2 nmol/L, P < 0.001)
      and a 42% reduction in RBC folate (2834.4 +/- 218.3 vs. 1651.8 +/- 75.9 nmol/L, P
      < 0.001). Hepatic spermidine and spermine in folate-depleted rats were 58 (P <
      0.001) and 67% (P < 0.01) higher, respectively, than in controls. Plasma
      putrescine was 27% higher (P < 0.05) than in controls. The polyamine
      concentrations of the jejunum, ileum, colon and brain did not differ. This study
      suggests that mild folate deficiency influences polyamine synthesis, but contrary
      to our hypothesis, hepatic spermidine and spermine were increased, as was
      circulating putrescine. This may have occurred for a number of reasons including
      increased enzyme activity or overcompensation by the betaine-homocysteine
      transmethylation pathway in the liver. Further study is necessary to clarify
      interactions between folate and polyamine metabolism and to determine whether
      polyamines are involved in the damaging effects of folate deficiency.

PMID- 12221223
TI  - A poorly fermented gel from psyllium seed husk increases excreta moisture and
      bile acid excretion in rats.
AB  - Psyllium seed husk (PSH) increases stool output and lowers blood cholesterol
      levels in humans. PSH and three fractions isolated from it were meal-fed to
      colectomized rats and fermented in vitro to test the hypothesis that viscous, gel
      forming fraction B was responsible for these physiological actions. Control rats
      were fed 50 g/kg cellulose. The concentration of each PSH fraction in the test
      meals was equivalent to its concentration in PSH. Yields of the fractions were:
      A, 171; B, 575; and C, 129 g/kg of PSH. The wet weight and moisture content of
      ileal excreta (IE) from rats fed test meals containing PSH or fraction B were
      greater than those measured in excreta from rats fed meals containing cellulose
      or the other two PSH fractions. Total bile acids in IE did not differ between
      rats fed PSH or fraction B and were greater in these groups than in the other
      groups. Fraction A was not fermented during 3 d of incubation; fraction B was
      poorly fermented, with approximately 30% of the constituent sugars disappearing;
      and fraction C was rapidly and nearly completely fermented. These results
      indicate that the gel-forming fraction we isolated from PSH is the
      physiologically active component of the husks.

PMID- 12221224
TI  - Moderate cholecalciferol supplementation depresses intestinal calcium absorption
      in growing dogs.
AB  - Hormonal regulation of calcium (Ca) absorption was investigated in a
      cholecalciferol (vitamin D(3))-supplemented group (hVitD) vs. a control group
      (cVitD) of growing Great Danes (100 vs. 12.5 micro g vitamin D(3)/kg diet).
      Although Ca intakes did not differ, fractional Ca absorption was significantly
      lower in the hVitD group than in the cVitD group. There were no differences in
      plasma concentrations of Ca, inorganic phosphate, parathyroid hormone, growth
      hormone or insulin-like growth factor I between groups. Plasma 25
      hydroxycholecalciferol [25(OH)D(3)] concentrations were maintained in the hVitD
      dogs at the same levels as in the cVitD dogs due to increased turnover of
      25(OH)D(3) into 24,25-dihydroxycholecalciferol [24,25(OH)(2)D(3)] and 1,25
      dihydroxycholecalciferol [1,25(OH)(2)D(3)]. In hVitD dogs, the greater plasma
      24,25(OH)(2)D(3) concentration and the enhanced metabolic clearance rate (MCR) of
      1,25(OH)(2)D(3) indicated upregulated 24-hydroxylase activity. The increased MCR
      of 1,25(OH)(2)D(3) decreased plasma 1,25(OH)(2)D(3) concentrations. In hVitD
      dogs, the greater production rate of 1,25(OH)(2)D(3) was consistent with the 12.9
      fold greater renal 1alpha-hydroxylase gene expression compared with cVitD dogs
      and compensated to a certain extent for the accelerated MCR of 1,25(OH)(2)D(3).
      The moderately decreased plasma 1,25(OH)(2)D(3) concentration can only partially
      explain the decreased Ca absorption in the hVitD dogs. Intestinal vitamin D
      receptor concentrations did not differ between groups and did not account for the
      decreased Ca absorption. We suggest that 24,25(OH)(2)D(3) may downregulate Ca
      absorption.

PMID- 12221225
TI  - Trans polyunsaturated fatty acids have more adverse effects than saturated fatty
      acids on the concentration and composition of lipoproteins secreted by human
      hepatoma HepG2 cells.
AB  - The objective of this study was to assess the relative long-term effects of
      linoleic (cis, cis 18:2), linolelaidic (trans, trans 18:2), and palmitic (16:0)
      acids on hepatic lipoprotein production in HepG2 cells. All fatty acids increased
      the mass of triglycerides (TG) in the medium and the incorporation of [(3)H]
      glycerol into secreted TG; the increase was more pronounced with linoleic acid
      than with linolelaidic and palmitic acids. The net accumulation in the medium of
      apolipoprotein (apo) A-I was not affected by the fatty acids tested and moderate
      changes in that of apoB resulted in apoB/apoA-I mass ratios of 1.05, 1.27 and
      0.86 with linoleic, linolelaidic and palmitic acids, respectively. The
      incorporation of [(14)C]-acetate into cellular plus secreted total sterols was
      9.1%, 33.6% and 17.4% of total [(14)C]-labeled lipids with linoleic, linolelaidic
      and palmitic acids, respectively. Relative to linoleic acid, palmitic acid, and
      to a greater extent (P < 0.05) linolelaidic acid, increased the secretion and
      cellular accumulation of [(14)C]-labeled free cholesterol (FC) and cholesteryl
      esters and decreased those of TG and phospholipids (PL). Compared with linoleic
      acid, linolelaidic acid increased LDL-cholesterol (C) and HDL-C by 154% (P <
      0.001) and 50% (P = 0.016), respectively, whereas palmitic acid increased LDL-C
      by 17% (P > 0.1) and did not affect HDL-C. The LDL-C to HDL-C ratios were 0.70,
      1.18 and 0.96 with linoleic, linolelaidic and palmitic acids, respectively. These
      differences were not due to altered LDL receptor activity. The PL to C ratios of
      HDL particles were 1.61, 0.40 and 0.77 with linoleic acid, linolelaidic acid and
      palmitic acid, respectively. These results suggest that relative to cis
      polyunsaturated and saturated fatty acids, trans PUFA more adversely affect the
      concentration and composition of apoA-I- and apoB-containing lipoproteins
      secreted by HepG2 cells.

PMID- 12221226
TI  - Energy restriction reduces fractional calcium absorption in mature obese and lean
      rats.
AB  - Weight loss is associated with bone loss and the risk may be greater in lean than
      heavier individuals, but the mechanisms involved remain unclear. We hypothesized
      that energy restriction (EnR) would decrease true fractional Ca absorption (TFCA)
      and be mediated by Ca-regulating hormones, but differently in obese and lean
      rats. Rats were fed a high fat (47% energy) or low fat (16% energy) diet for 4
      mo. At 6 mo of age, the resulting lean [284 +/- 28g (mean +/- SD, n = 18)] and
      obese (319 +/- 34g, n = 20) groups (P < 0.005) were divided into controls (CTL,
      ad libitum) and energy-restricted (40% restriction) groups. At baseline, bone
      resorption (urinary crosslinks) was higher and bone formation (serum osteocalcin)
      was lower in obese than in lean rats, whereas Ca balance components and Ca
      regulating hormones did not differ. EnR for 10 wk reduced body weight by 25 +/-
      7% compared with a 6 +/- 6% gain in CTL rats (P < 0.001). For both lean and obese
      rats, TFCA (5-d measurement, (45)Ca radioisotope) decreased from 30 +/- 9% to 24
      +/- 9% with EnR, compared with 25 +/- 10% to 29 +/- 11% in controls (P < 0.05).
      Weight loss was directly correlated with the decrease in TFCA (r = 0.34, P <
      0.05). Uterine weights indicated a reduced estrogenic activity in energy
      restricted rats (P < 0.0001). In lean, but not obese rats, serum estradiol (E(2))
      correlated with weight loss (r = 0.52, P < 0.05), and tended to correlate with
      the decrease in TFCA (r = 0.48, P = 0.06). At the end of the study, serum 25
      hydroxyvitamin-D was lower and urinary Ca was higher in lean than obese energy
      restricted rats. Distinct endocrine profiles during weight loss in obese and lean
      rats suggest that the susceptibility of bone and Ca metabolism to EnR could
      differ depending on initial body weight.

PMID- 12221227
TI  - Modulation of essential (n-6):(n-3) fatty acid ratios alters fatty acid status
      but not bone mass in piglets.
AB  - Dietary (n-6) and (n-3) fatty acids have been implicated as important regulators
      of bone metabolism. The main objective of this research was to define the
      response of whole-body growth, fatty acid status and bone mass to a reduced
      dietary (n-6):(n-3) fatty acid ratio. A secondary objective was to determine
      whether there is an amount of fat x fatty acid ratio interaction for these
      outcomes. Piglets (n = 32) were randomized to 1 of 4 diets: group 1: [30 g fat/L
      + (n-6):(n-3) ratio 4.5:1]; group 2: [30 g fat/L + (n-6):(n-3) ratio 9.0:1];
      group 3: [60 g fat/L + (n-6):(n-3) ratio 4.5:1]; and group 4: [60 g fat/L + (n
      6):(n-3) ratio 9.0:1]. After 21 d, outcomes assessed included growth, fatty acid
      status and bone mass and metabolism. Growth and bone mass did not differ among
      the four groups nor did arachidonic acid (AA as g/100 g fatty acids) in plasma,
      adipose and brain. Piglets fed diets 1 and 3 with the lower (n-6):(n-3) ratio had
      lower liver AA (P < 0.001). Those fed diets 1 and 2 containing 30 g fat/L had
      lower docosahexaenoic acid (DHA as g/100 g fatty acids) in liver (P < 0.001),
      plasma (P = 0.019) and adipose tissue (P = 0.045). However, piglets fed diets 1
      and 3 had higher (P < 0.001) brain DHA than those fed diets with a higher (n
      6):(n-3) ratio. Higher plasma DHA was associated with less bone resorption (r = 
      0.44, P = 0.01). Therefore, elevation of dietary (n-3) fatty acids supports
      growth and fatty acid status while not compromising bone mass. The results may be
      of relevance to the nutritional management of preterm infants whose DHA status is
      often too low and bone resorption too high.

PMID- 12221228
TI  - Preterm birth affects the intestinal response to parenteral and enteral nutrition
      in newborn pigs.
AB  - Maturation of gastrointestinal (GI) function in neonates is stimulated by enteral
      nutrition, whereas parenteral nutrition induces GI atrophy and malfunction. We
      investigated whether preterm birth alters the GI responses to parenteral and
      enteral nutrition. Pigs were delivered either preterm (107 d gestation) or at
      term (115 d gestation) and fed total parenteral nutrition (TPN) or enteral sow's
      milk (ENT) for 6 d after birth. Immaturity of the preterm pigs was documented by
      reduced blood pH, oxygen saturation and neutrophil granulocyte function, impaired
      intestinal immunoglobulin G uptake from colostrum, and altered relative weights
      of visceral organs (small intestine, liver, spleen, pancreas, and adrenals). For
      both ages at delivery, increases occurred in pancreatic weight (30-75%) and
      amylase activity (0.5- to 13-fold) after birth, but much more in ENT than in TPN
      pigs (P < 0.05). Six days of TPN feeding was associated with reduced intestinal
      weight for both delivery groups (60% of values in ENT, P < 0.001), but only in
      term TPN pigs was the weight lower than at birth (-20%, P < 0.05). Likewise, it
      was only in term TPN pigs that intestinal maltase activity increased, compared
      with ENT, and the absorption of glucose and proline decreased. Only in preterm
      pigs did TPN feeding increase lactase activity (+50% compared with ENT, P <
      0.05). For both delivery ages, the mRNA of lactase-phloridzin hydrolase and
      sodium-coupled glucose transporter 1 were increased in TPN, compared with ENT. In
      conclusion, the trophic effect of enteral vs. parenteral nutrition on the GI
      tract is also present after preterm birth, but the postnatal maturation of many
      GI functions is modified, compared with term birth. The effects of nutritional
      regimen on the maturation of the gut epithelium in neonates depend on gestational
      age at birth.

PMID- 12221229
TI  - A CLA mixture prevents body triglyceride accumulation without affecting energy
      expenditure in Syrian hamsters.
AB  - We examined the effects of feeding conjugated linoleic acids (CLA) to adult male
      hamsters on several components of energy metabolism and body composition.
      Hamsters (n = 54) were assigned for 6-8 wk to one of three diets: 1) a standard
      diet (in percentage energy: lipids, 33, carbohydrates, 49, and proteins, 18); 2)
      to the standard diet augmented with the 9c,11t-isomer of CLA to 1.6% of energy (R
      group); or 3) the standard diet augmented with the 9c,11t-isomer and the 10t,12c
      CLA isomer to 3.2 (1.6 + 1.6) % of energy (CLA mix group). (15)N uniformly
      labeled milk-protein was included in the diet to measure the incorporation of
      dietary protein into liver and muscle. Basal metabolic rate, thermogenic response
      to feeding and energy expenditure during spontaneous activity or during an
      exercise at approximately 60% of VO(2max) were measured. Carnitine
      palmitoyltransferase-I (CPT-I), leptin, insulin and triiodothyronine
      concentrations, as well as the in vivo overall adiposity changes were also
      determined. After 6 wk, the whole-body triglyceride content determined in vivo by
      NMR was significantly higher in the R group than in the control and CLA mix
      groups. The CLA mix group differed from the others in the lack of body
      triglyceride accumulation between d 21 and d 45 of the study, and the appearance
      of a slight insulin-resistance (homeostatic model assessment index, P < 0.05).
      Paradoxically, the lack of effect on whole-body lipid oxidation was associated
      with a greater CPT-I-specific activity in tissues of both CLA-fed groups (P <
      0.05). No other major effects of CLA feeding were detected. In conclusion, CLA
      supplementation in hamsters did not affect adipose weight or the components of
      energy expenditure despite a theoretically higher capacity of red muscle to
      oxidize lipids. Only a CLA mixture prevented whole-body triglyceride accumulation
      over time.

PMID- 12221230
TI  - Tetrahydrofolates are greatly stabilized by binding to bovine milk folate-binding
      protein.
AB  - The dietary supply of folates and their measurement are both affected,
      potentially, by the instability of some folates. Labile folates appear to be
      stabilized by binding to folate-binding protein (FBP); this paper reports
      measurements of that stabilization. The degradation rates of the very labile
      tetrahydrofolate (H(4)folate) and moderately labile 5-methyltetrahydrofolate (5
      CH(3)H(4)folate) were measured with the compounds free or bound to either soluble
      or immobilized bovine milk FBP. Complexation increased stability from 2- to >
      1000-fold, depending on buffer and temperature conditions. H(4)folate at 4
      degrees C and pH 6.7 appeared to be quite stable for > 100 d when bound to
      soluble FBP but had a half-life of < 1 h when free. Stabilization of milk folates
      may be a role of FBP and would improve the bioavailability of milk folate to
      newborns and other consumers.

PMID- 12221231
TI  - Intestinal brush border membrane catalyzes hydrolysis of pyridoxine-5'-beta-D
      glucoside and exhibits parallel developmental changes of hydrolytic activities
      toward pyridoxine-5'-beta-D-glucoside and lactose in rats.
AB  - Pyridoxine-5'-beta-D-glucoside (PNG) is a major form of vitamin B-6 in plant
      foods that exhibits partial bioavailability as vitamin B-6 in humans. We
      previously identified an intestinal mucosal cytosolic PNG hydrolase that
      catalyzes the partial hydrolysis of PNG absorbed without prior deglycosylation.
      Recent observations that the brush border membrane also catalyzes PNG hydrolysis
      led to the hypothesis that PNG hydrolysis may be another function of the beta
      glucosidase lactase-phlorizin hydrolase (LPH) and, thus, brush border PNG
      hydrolysis would undergo a developmental decline similar to that of lactose
      hydrolysis. In this study, the relationships among hydrolytic activities in small
      intestinal cytosolic and brush border fractions in rats (n = 9 per group) of
      various ages (1-2 d and 2, 4, 8, 12 and 24 wk) were examined. In vitro specific
      activities toward PNG and lactose were greater in brush border than cytosol, and
      these were greater in newborn rats than in all other age groups (P < 0.01). Brush
      border activities toward PNG and lactose and were closely correlated (r = 0.84; P
      < 0.0001). These findings suggest that the hydrolysis of PNG is catalyzed at
      least partially at the brush border and that the bioavailability of PNG may be
      influenced by the residual LPH activity in children and adults.

PMID- 12221232
TI  - All-trans beta-carotene appears to be more bioavailable than 9-cis or 13-cis beta
      carotene in gerbils given single oral doses of each isomer.
AB  - Male gerbils (28 d old) were used to investigate the beta-carotene (betaC) isomer
      pattern in the intestine and tissues 6 h after ingestion of three betaC isomers.
      After a 49- to 52-d period of consuming the AIN93G diet without vitamin A (VA) or
      betaC, three groups (n = 7) were gavaged with crystalline all-trans (at)betaC, 9
      cis (9c)betaC or 13-cis (13c)betaC solubilized in oil and a control group (n = 5)
      with oil alone. Total betaC per dose for gerbils in the atbetaC, 9cbetaC and
      13cbetaC groups was 384 +/- 3, 391 +/- 2 and 386 +/- 2 nmol, respectively. After
      6 h, gerbils were killed and serum, stomach contents, small intestinal contents
      (SIC), small intestinal mucosal scrapings (SIM) and liver were collected. betaC
      and VA in tissues were quantified using HPLC. Nonspecific isomerization of betaC
      occurred in the digestive tracts of gerbils administered betaC; the greatest
      effect was in the SIC of the 13cbetaC (50:50 cis:trans) and 9cbetaC (70:30
      cis:trans) groups. Concentrations of total betaC in the SIM of gerbils
      administered at betaC were greater than those intubated with 9cbetaC and 13cbetaC
      (P < 0.05). Gerbils that received atbetaC had greater total betaC concentrations
      in serum (P < 0.05) and total betaC stores in liver (P < 0.01) compared with
      those administered 9cbetaC and 13cbetaC. Gerbils intubated with 9cbetaC had
      higher levels of total betaC in serum (P = 0.05) and liver (P < 0.01) compared
      with those intubated with 13cbetaC. Because of its preferential uptake, transport
      and tissue accumulation, atbetaC appears to be a more bioavailable isomer than
      9cbetaC or 13cbetaC in gerbils.

PMID- 12221233
TI  - The relative vitamin A value of 9-cis beta-carotene is less and that of 13-cis
      beta-carotene may be greater than the accepted 50% that of all-trans beta
      carotene in gerbils.
AB  - The effectiveness of beta-carotene (betaC) as a vitamin A (VA) precursor may be
      influenced by the proportions of cis isomers of betaC consumed in the diet.
      Although the metabolic fates of cis isomers of betaC are poorly understood, their
      retinol equivalency has been assigned a value 50% that of all-trans (at) betaC. A
      dose-response design was used to estimate the relative VA value (VAV) of atbetaC,
      9-cis (9c) betaC and 13-cis (13c) betaC in gerbils using total liver retinol as a
      measure of VAV. Ten groups of gerbils received a daily dose of oil with or
      without betaC isomer by gavage for 7 d. Nine groups (n = 5) were divided equally
      among the three betaC dosing treatments with each isomer provided at 141, 275 and
      418 nmol/d. Total liver VA (171-259 nmol) in gerbils administered atbetaC was
      higher than total liver betaC (25-53 nmol). Stores of VA and betaC in livers from
      gerbils administered atbetaC were higher than stores of VA and betaC in livers
      from those given 9cbetaC or 13cbetaC. The relative VAV of cis betaC isomers was
      estimated by comparing slopes of dose-response lines of all three betaC isomers
      using atbetaC as a reference. Total liver VA and betaC increased linearly (P <
      0.05) with increasing betaC intake in gerbils gavaged with all three betaC isomer
      oils. The relative VAV of 9cbetaC was less (38%) and 13cbetaC was more (62%) than
      the assigned value of 50% that of atbetaC. Thus, the proportions of cis isomers
      of betaC contained in a food could negatively affect the vitamin A value of the
      diet.

PMID- 12221234
TI  - A high retinol dietary intake increases its apical absorption by the proximal
      small intestine of juvenile sunshine bass (Morone chrysops x M. saxatilis).
AB  - The relationship between dietary intake and systemic availability of retinol is
      likely to be complex because although retinol is an essential nutrient, it is
      toxic at high levels. The present study determined whether rates of transapical
      retinol absorption are modulated so that availability is increased at low dietary
      levels, but decreased when dietary intake is excessive. Juvenile hybrid striped
      bass were fed for 6 wk diets with 568 (below), 1657 (approximating the
      requirement) and 40,244 (excessive) micro g/kg dry diet of trans retinol.
      Proximal small intestine segments were used to measure rates of retinol
      absorption and tissue concentrations. Initial and final body mass did not differ
      among groups; deficiency and toxicity symptoms were not observed. Uptake of
      tracer retinol was inhibited by unlabeled retinol, indicating the presence of
      saturable, carrier-mediated absorption. Increasing dietary levels of retinol
      increased the rates of absorption measured at 0.05 mmol/L [8.04 +/- 0.65; 15.2 +/
      1.53; 25.1 +/- 3.4 pmol/(mg. min) for below, approximating and exceeding the
      retinol requirement; P < 0.0001]; this resulted in higher tissue concentrations
      of all-trans retinol (0.21 +/- 0.03, 0.49 +/- 0.21 and 338 +/- 89 pmol/g; P <
      0.0001) and dehydro-retinol (0.11 +/- 0.04, 0.91 +/- 0.04, and 454 +/- 109
      pmol/g; P < 0.001). These findings suggest that the systemic availability of
      various dietary levels of retinol is modulated after transapical absorption.

PMID- 12221235
TI  - Minimal enteral feeding induces maturation of intestinal motor function but not
      mucosal growth in neonatal dogs.
AB  - Providing small enteral feedings for parenterally fed preterm infants during the
      first few weeks of life improves feeding tolerance. However, it is not known
      whether these feedings achieve this result via stimulation of gut growth and/or
      maturation of function. The minimal level needed to attain these responses is
      also critical to identify, because neonatologists often limit feeding volumes to
      minimize the risk of necrotizing enterocolitis. Thus, we determined the dose
      response relationships between enteral feeding volume and gastrointestinal growth
      and small intestine motor function. Newborn canine pups (n = 51) received 0, 2.5,
      5.0, 7.5, 10, 30 or 100% of their daily fluid intake enterally with the remainder
      given parenterally for 4-5 d. Motor activity was recorded, blood drawn for
      determination of gastrin and motilin, and intestinal tissue harvested for
      determination of DNA and protein content and morphology. Feeding volumes that
      provided 30% or more of daily fluid intake significantly increased small
      intestinal mucosal growth above that of unfed pups, but feeding volumes that
      provided as little as 10% of daily fluid intake significantly induced maturation
      of motor patterns beyond that of unfed pups. Plasma concentrations of gastrin and
      motilin did not differ among groups. We conclude that small enteral feedings
      typically used for minimal enteral feeding strategies improve feeding tolerance
      by triggering maturation of motor function but not gut growth in neonatal dogs.
      Small feeding volumes trigger this maturation as well as large volumes.

PMID- 12221236
TI  - The mycotoxin deoxynivalenol affects nutrient absorption in human intestinal
      epithelial cells.
AB  - Deoxynivalenol (DON) is a mycotoxin belonging to the tricothecene family that has
      many toxic effects in animals, including diarrhea and weight loss. Using the
      human epithelial intestinal cell line HT-29-D4 as an in vitro model, we studied
      the effect of DON on the uptake of different classes of nutrients, including
      sugars, amino acids and lipids. At low concentrations (below 10 micro mol/L), DON
      selectively modulated the activities of intestinal transporters: the D-glucose/D
      galactose sodium-dependent transporter (SGLT1) was strongly inhibited by the
      mycotoxin (50% inhibition at 10 micro mol DON, P < 0.05), followed by the D
      fructose transporter GLUT5 (42% inhibition at 10 micro mol/L, P < 0.001), active
      and passive L-serine transporters (30 and 38% inhibition, respectively, at 10
      micro mol/L, P < 0.05). The passive transporters of D-glucose (GLUT) were
      slightly inhibited by DON (15% inhibition at 1 micro mol/L, P < 0.01), whereas
      the transport of palmitate was increased by 35% at 10 micro mol/L DON (P <
      0.001). In contrast, the uptake of cholesterol was not affected by the mycotoxin.
      At high concentrations (100 micro mol/L), SGLT1 activity was inhibited by 76% (P
      < 0.01), whereas the activities of all other transporters were increased. The
      selective effects of DON on intestinal transporters were mimicked by
      cycloheximide and deoxycholate, suggesting that inhibition of protein synthesis
      and induction of apoptosis are the main mechanisms of DON toxicity in intestinal
      cells.

PMID- 12221237
TI  - Liver fat and plasma ethanol are sharply lower in rats fed ethanol in conjunction
      with high carbohydrate compared with high fat diets.
AB  - The effects of high fat and high carbohydrate diets on alcohol metabolism were
      studied on blood alcohol and liver fat concentration. In Experiment 1, rats
      consumed an alcohol-containing liquid diet. Blood was collected for ethanol,
      glucose and lactate analyses and livers were excised for lipid determination.
      Blood ethanol and liver fat were lower when rats consumed the high carbohydrate
      diet. Glucose concentrations were lower in rats fed the high fat diet compared
      with those fed the high carbohydrate diet when ethanol was consumed. In
      Experiment 2, rats consumed a high fat, ethanol-containing diet for 13 d. Half of
      the rats were switched to a high carbohydrate, ethanol-containing diet for an
      additional 11 d. The same analyses were carried out as for Experiment 1.
      Switching the high fat-fed rats to the high carbohydrate diet reversed the high
      blood ethanol and high liver fat values, even though the rats consumed
      significantly more alcohol with the high carbohydrate diet. In Experiment 3 the
      same high fat and high carbohydrate diets without ethanol were consumed for 2 wk,
      at which time ethanol was administered acutely, intraperitoneally, at 2 g/kg.
      Blood was analyzed for ethanol, glucose and lactate 30, 60 and 120 min after
      injection. Rats fed the high carbohydrate diet had lower blood ethanol but higher
      lactate at 120 min compared with those fed the high fat diet. The results suggest
      that the rate of ethanol elimination is slower in rats fed high fat than in those
      fed high carbohydrate diets, resulting in elevated blood ethanol and liver fat
      levels for the former.

PMID- 12221239
TI  - Vitamin A deficiency exacerbates inflammation in a rat model of colitis through
      activation of nuclear factor-kappaB and collagen formation.
AB  - Inflammatory bowel disease is characterized by oxidative stress, inflammation and
      tissue damage. Vitamin A is an antioxidant, a regulator of epithelial
      proliferation and differentiation and vital for optimal immune function. To
      investigate the effect of vitamin A on the course of colitis, it was induced by
      administration of trinitrobenzene sulfonic acid (TNBS) into the colons of rats
      fed for 7 wk vitamin A-deficient (VAD), sufficient (VAS) or supplemented (VASUP)
      diet, or VAS pair-fed (PF) to the VAD rats. Inflammation and fibrosis were
      examined by hematoxin and eosin, and Sirius red staining. Activation of nuclear
      factor-kappaB (NF-kappaB) and oxidative stress were determined by electrophoretic
      mobility shift and plasma malondialdehyde (MDA) and RBC Cu/Zn-superoxide
      dismutase activity, respectively. Vitamin A deficiency in the noncolitic rats
      impaired food consumption and weight gain (P < 0.05) and increased plasma MDA, (P
      = 0.01) activity of NF-kappaB (P < 0.05) and deposition of collagen in the colon.
      Our data suggest that vitamin A deficiency induces colonic inflammation. Colitis
      is amplified by deficiency and ameliorated by supplementation of the vitamin.
      These findings have implications for the management of inflammatory bowel
      disease.

PMID- 12221238
TI  - Acute valproate administration impairs methionine metabolism in rats.
AB  - Valproate (VPA) is a drug widely used to treat epilepsy, but it has serious
      adverse effects including hepatotoxicity, teratogenicity and antifolate activity.
      The mechanism underlying VPA toxicity is unclear although an interaction with
      folate and other metabolites involved in methionine metabolism has been
      suggested. The present study was undertaken to evaluate potential changes in the
      metabolic function of the methionine cycle after acute exposure to a single dose
      of valproate. Female Wistar rats (n = 30) were treated with 400 mg/kg of VPA.
      Different groups of six rats were killed at 1 (t1), 3 (t3), 6 (t6), 9 (t9), and
      24 (t24) hours after the injection. One group of rats was untreated (n = 6) and
      was considered the control group. The most pronounced effects of VPA
      administration were observed 1 h after drug injection. VPA induced a 56%
      reduction in methionine adenosyltransferase activity and a 54% reduction in
      plasma vitamin B-6. Increases in the hepatic concentration of S
      adenosylhomocysteine and oxidized glutathione, and a reduction in the S
      adenosylmethionine/S-adenosylhomocysteine transmethylation ratio also occurred at
      1 h. All of these alterations, however, were normalized within 24 h, parallel
      with a decrease in serum VPA concentration. The acute effects of VPA suggest that
      the alterations in the methionine cycle could be the common mechanism underlying
      the hepatotoxic, teratogenic and antifolate effects of the drug.

PMID- 12221240
TI  - The capacity of noninflammatory (steady-state) dendritic cells to present antigen
      in the primary response is preserved in acutely protein- or energy-deficient
      weanling mice.
AB  - The objective of this investigation was to determine the influence of wasting
      protein and/or energy deficits on the capacity of dendritic cells to initiate
      primary responses. Weanling male and female C57BL/6J mice were permitted free
      access to a complete purified diet, free access to an isocaloric low protein
      purified diet (combined deficiencies of protein and energy) or restricted intake
      of the complete diet (energy deficiency) for up to 14 d; a 19-d-old zero-time
      control group was also included. Malnourished mice lost 1.5-2% of initial body
      weight daily. Antigen presentation by dendritic cells from spleen and lymph nodes
      was assessed in vitro by the primary one-way allogeneic mixed lymphocyte reaction
      using CBA/J mononuclear or CD4(+) T cells as responders. This function was
      sustained despite advanced weight loss and, remarkably, was increased in cell
      suspensions from 14-d energy-deficient mice. Antigen presentation by dendritic
      cells in mononuclear suspensions was examined in vivo using the host-vs.-graft
      response in CBA/J recipients, and an ontogeny-related increase was sustained in
      both malnourished groups through 14 d of weight loss. Neither wasting protocol
      influenced the proportion of mononuclear cells (1-2%) exhibiting dendritic cell
      phenotype (CD11c(+)F4/80(-/low)) in the cellular suspensions used to study
      antigen-presenting activity. Consequently, these functional studies are
      interpretable on a per dendritic cell basis. In the absence of infectious or
      inflammatory pressure, the dendritic cell retains antigen-presenting capacity
      despite acute (wasting) deficiencies of protein and/or energy. The results are
      relevant to presentation of both foreign (adjuvant role) and self (tolerizing
      role) antigens by the dendritic cell.

PMID- 12221241
TI  - Absolute counts and distribution of lymphocyte subsets in small intestine of
      BALB/c mice change during weaning.
AB  - The gut immune system is an essential part of the barrier function of the gut. At
      weaning, major changes can be expected in the number and subset composition of
      lymphocytes in the small intestine since the gut is exposed to a wide variety of
      food and microbial antigens, especially when human milk is gradually replaced by
      weaning foods. The purpose of this study was to evaluate the changes in small
      intestine lymphocyte subsets in mice during weaning. BALB/c male mice at weaning
      (3 wk old) were fed a nonpurified diet for 18 d and were killed at different
      times (0, 4, 7, 12 and 18 d). Lymphocyte populations from lamina propria (LPL),
      Peyer's patches (PPL) and intestinal epithelium (IEL) were isolated. The
      expression of different antigens (CD3, CD4, CD8alpha, CD8beta, CD22 and CD45R) in
      those lymphocyte populations was analyzed by flow cytometry. The percentages of
      cells expressing T-cell antigens, such as CD3, were significantly higher in LPL
      during weaning compared to d 0. The percentages of cells expressing CD8alpha and
      CD8beta increased in both IEL and LPL. However, the percentage of CD4+ cells
      tended (P = 0.07) to decrease in IEL and to increase in LPL. The percentages of
      cells expressing B-cell antigens, such as CD22 or CD45R in PPL increased. Changes
      in the specific phenotypes of intestinal lymphocyte populations at weaning are
      apparently related to the maturation of the intestinal immune system during early
      life. Thus, B cells increase in PPL and T cell increase in IEL and LPL.

PMID- 12221242
TI  - Zinc status influences zinc transport by porcine brain capillary endothelial
      cells.
AB  - Brain capillary endothelial cells (BCEC) were cultured as an in vitro model of
      the blood-brain barrier (BBB) and manipulated to investigate how the BBB responds
      to changes in zinc status. BCEC were grown in minimum essential medium (MEM) with
      2% fetal bovine serum and 13% platelet-poor horse serum. A moderate zinc
      deficiency was imposed by growing the cells in medium containing serums that had
      previously been dialyzed against EDTA to remove endogenous labile zinc. The
      control treatment was MEM with undialyzed serums (3 micro mol Zn/L); low-Zn was
      MEM with dialyzed serums (1.5 micro mol Zn/L); Zn-back was MEM with dialyzed
      serums, plus ZnCl(2) added back (3 micro mol Zn/L); high-Zn was MEM with
      undialyzed serums, plus ZnCl(2) (50 micro mol Zn/L). Low-Zn treatment increased
      (P < 0.02) the rate of zinc uptake into BCEC, relative to control and Zn-back;
      low-Zn treatment also increased (P < 0.05) the rate of zinc transport across the
      BCEC into the abluminal chamber (analogous to the brain), relative to control and
      Zn-back. High-Zn decreased (P < 0.02) the rate of zinc transport across BCEC into
      the brain, while increasing (P < 0.001) the rate of zinc uptake into BCEC,
      relative to controls. We conclude that BCEC responded to changes in zinc status
      by altering the rate of zinc transport in a manner consistent with the BBB
      actively working to sustain brain zinc homeostasis.

PMID- 12221243
TI  - H and L ferritin subunit mRNA expression differs in brains of control and iron
      deficient rats.
AB  - The mRNA expression of ferritin subunits has not been studied thoroughly in the
      brain regions of iron-deficient rats. Sprague-Dawley rats (n = 26; 21 d old) were
      randomly assigned to an iron-deficient (3.5 mg Fe/kg diet) or a control diet (35
      mg Fe/kg diet) for 6 wk. Ferritin protein and mRNA contents were quantified and
      the cellular expression of ferritin subunits in brain was determined. H and L
      ferritin had the same mRNA locations in nearly all brain regions. Both ferritin
      subunit mRNAs had heterogeneous distributions and there was a regional effect
      across brain regions. Iron deficiency did not affect the amount of ferritin mRNA
      in most brain regions, suggesting the post-transcriptional regulation of
      messengers by iron status. H ferritin protein was predominant in neurons and
      oligodendrocytes, whereas L ferritin protein and iron predominated in microglia
      cells and astrocytes as well as in oligodendrocytes and neurons. Ferritin mRNA
      was detectable only in neurons. Iron deficiency did not induce new types of cells
      containing either ferritin protein or mRNA. The fact that ferritin protein was
      found in four types of cells whereas mRNA was found in only one type of cell
      suggests that the site of ferritin synthesis is different from protein location
      in the brain. All of these data suggest that regulation of ferritin subunits is
      cellular and/or regional specific.

PMID- 12221244
TI  - Dietary peptides induce satiety via cholecystokinin-A and peripheral opioid
      receptors in rats.
AB  - We hypothesized that the digestion of proteins gives rise to peptides that
      initiate several satiety signals from the gut, and that the signals arising will
      be dependent on the protein source. The role of peripheral opioid and
      cholecystokinin (CCK)-A receptors was investigated. Casein, soy protein, and
      casein and soy hydrolysates were administered to rats by gavage (0.5 g protein/4
      mL water). Food intake was measured over 2 h. The opioid receptor antagonist,
      naloxone methiodide (1.0 mg/kg) given intraperitoneally (i.p.), increased food
      intake when given at the same time as the hydrolysate preloads, 25 min after the
      casein preloads and 55 min after the soy protein preloads. The CCK-A receptor
      antagonist, devazepide (which reverses protein-induced food intake suppression),
      when given at 0.25 mg/kg, i.p., 60 min before preloads of each of three soy
      hydrolysates, also blocked suppression of food intake, but the strength and
      duration of the interaction depended on the preparation. When the two receptor
      antagonists were both administered with soy or casein preloads, their effects
      were additive. We conclude that peptides arising from digestion contribute to
      satiety by independent activation of both opioid and CCK-A receptors.

PMID- 12221245
TI  - Folate deficiency alters melatonin secretion in rats.
AB  - The final step of melatonin (MLT) synthesis is methylation of N-acetyl-serotonin,
      with S-adenosylmethionine as a methyl donor provided by a metabolic pathway
      involving sulfur-containing amino acids (homocysteine and methionine).
      Remethylation of homocysteine to methionine requires folate. The present study
      was undertaken to test the influence of folate deficiency on MLT secretion.
      Severe folate deficiency was induced in rats by feeding them a synthetic diet
      containing (per kg diet) 0 mg folate and 10 g succinylsulfathiazole. Control rats
      were fed the same diet containing 8 mg folate/kg. After 4 wk, erythrocyte folate
      concentrations were significantly lower and plasma homocysteine levels were
      greater in folate-deficient rats than in controls. Pineal MLT concentration and
      urinary excretions of MLT, 6 sulfatoxymelatonin (the main hepatic MLT metabolite)
      and methoxylated catechol compounds were lower in the folate-deficient group than
      in the controls, whereas plasma catecholamine concentrations did not differ.
      Decreases generally were more marked at wk 2 than at wk 4 for the urinary
      metabolite excretions. These findings indicate that folate deficiency
      dramatically alters MLT secretion in rats.

PMID- 12221246
TI  - Fortification masks nutrient dilution due to added sugars in the diet of children
      and adolescents.
AB  - High intakes of added sugars have often been suspected of lowering nutrient
      density, especially in the diet of children and adolescents. Because fortified
      foods, which currently contribute considerably to the intake of vitamins and
      minerals, are often also sweetened with added sugars, they could counteract this
      nutrient dilution. Data from the DOrtmund Nutritional and Anthropometric
      Longitudinally Designed (DONALD)-Study were used to assess the effects of added
      sugars, fortified food and energy intakes, time and age on nutrient densities. A
      total of 4993 3-d weighed dietary records from 849 children and adolescents 2-18
      y old, collected between 1985 and 2001 were analyzed using a mixed linear model,
      in which the means of the data and the covariance structure specific to the
      DONALD-Study was modeled. In general, nutrient densities in the diets of children
      and adolescents were above recommended nutrient densities. Added sugars intake
      [in percentage of energy intake (E%)] was positively associated with energy
      intake (MJ/d; P < 0.05) and intake of fortified food (E%; P < 0.0001). Positive
      effects of fortification on nutrient densities (usually P < 0.0001) exceeded the
      negative effects of added sugars intake (usually P < 0.01) for most nutrients, in
      some cases even twofold. Associations between energy intake and nutrient
      densities were negative and, with the exception of thiamin in 2- to 3-y-olds,
      statistically significant. Time and age trends were heterogeneous. Our data did
      not show significant nutrient dilution because of added sugars. The positive
      effect of fortification on nutrient densities was greater than the negative
      effect of added sugars. Therefore, fortification should more often be considered
      in dietary analyses.

PMID- 12221247
TI  - Folic acid intake from fortification in United States exceeds predictions.
AB  - In 1996, the U.S. Food and Drug Administration issued a regulation requiring that
      all enriched cereal-grain products be fortified with folic acid by January 1998.
      An average increase in folic acid intake of 100 micro g/d was projected as a
      result of this fortification. The objective of the present study was to estimate
      the effect of this fortification on the intake of folic acid and total folate,
      and on the prevalence of individuals with inadequate folate intake and with high
      folic acid intake. We used data on food and nutrient intake from 1480 individuals
      who participated in the 5th and 6th examinations of the Framingham Offspring
      Cohort Study. Fortification was instituted during the 6th examination so that 931
      participants were examined before its implementation (nonexposed) and 549 after
      implementation (exposed). Published data on total folate in enriched cereal-grain
      products were used to correct folate content in these foods to reflect
      fortification. Among nonsupplement users, folic acid intake increased by a mean
      of 190 [95% confidence interval (CI): 176, 204] micro g/d (P < 0.001) and total
      folate intake increased by a mean of 323 (95% CI: 296-350) micro g dietary folate
      equivalents (DFE)/d (P < 0.001) in the exposed participants. Similar increases
      were seen among supplement users exposed to fortification. The prevalence of
      exposed individuals with total folate intake below the estimated average
      requirement (320 micro g DFE/d) decreased from 48.6% (95% CI: 44.2-53.1%) before
      fortification to 7.0% (95% CI: 3.1-10.9%) after fortification in individuals who
      did not use folic acid supplements. This prevalence was approximately 1% or less
      for users of supplements both before and after fortification. Prevalence of
      individuals with folic acid intake above the upper tolerable intake level (1000
      micro g folic acid/d) increased only among supplement users exposed to
      fortification (from 1.3 to 11.3%, P < 0.001). No changes in folic acid intake
      were observed over time in the nonexposed participants. By these estimations,
      folic acid fortification resulted in a mean increase in folic acid intake that
      was approximately twice as large as previously projected.

PMID- 12221248
TI  - Elevated serum methylmalonic acid concentrations are common among elderly
      Americans.
AB  - To describe serum methylmalonic acid (MMA) concentrations of elderly Americans
      and examine relationships between serum MMA and other factors, we used surplus
      serum samples collected from elderly (n = 1145) and young-adult (n = 1026)
      participants in Phase 2 of the third National Health and Nutrition Examination
      Survey (1991-1994). In approximately 20% of participants >/=65 y old, serum MMA
      was >370 nmol/L, the 90th percentile of the distribution of participants aged 30
      39 y. Consistent with previous reports, we observed strong, independent positive
      associations between serum MMA concentration and serum concentrations of
      creatinine and homocysteine. After controlling for demographic factors and
      creatinine, geometric mean MMA concentration was lower in non-Hispanic blacks
      [223.6 nmol/L; 95% confidence interval (CI), 198.8-251.5] than non-Hispanic
      whites (265.1 nmol/L; 95% CI, 240.3-292.4). However, the prevalence of elevated
      levels did not vary with race/ethnicity. Serum MMA concentration bore a strong
      inverse relation to serum vitamin B-12 concentration. Nevertheless, elevated
      serum MMA concentrations affected approximately 15% of those with both normal
      serum creatinine concentrations and serum B-12 concentrations >148 pmol/L. We
      conclude that many elderly Americans demonstrate metabolic evidence of low B-12
      status, that elevations occur frequently in the absence of traditional deficiency
      indicators and that levels vary with race/ethnicity and renal function.

PMID- 12221249
TI  - Dietary inulin suppresses azoxymethane-induced preneoplastic aberrant crypt foci
      in mature Fisher 344 rats.
AB  - Preneoplastic aberrant crypt foci (ACF) are generally accepted as reliable
      markers for colon carcinogenesis in animal models. Rat model ACF studies,
      however, use younger rats, and there are no published reports on the suitability
      of adult rats for ACF studies. In this study, inulin, a known suppressor of
      azoxymethane (AOM)-induced ACF, was tested for its ability to suppress ACF
      formation in mature rats. After a 2-wk acclimation period, 12-mo-old Fisher 344
      retired male breeders received two subcutaneous injections of AOM dissolved in
      saline at weekly intervals. In experiment 1, six groups received 0, 4, 8, 10, 12
      and 16 mg AOM/kg body at each injection and were fed AIN-93M diet. In experiment
      2, four groups of rats were fed 10 mg AOM/kg body at each injection based on the
      results of experiment 1, and were fed 0, 2.5, 5 and 10 g long-chain inulin
      diets/100 g. All the rats were killed after 11-wk feeding periods. In experiment
      1, there was a significant (P < 0.05) AOM dose response on ACF formation. Rats
      fed >10 mg of AOM had greater (P < 0.05) mortality. In experiment 2, there was a
      significant increase in cecal weight and a decrease in cecal pH from 7.17 in the
      control group to 6.87, 6.61 and 5.76 in the groups fed inulin at 2.5, 5.0 and 10
      g/100 g, respectively. Long-chain inulin dose-dependently reduced ACF incidence
      in the colon (P < 0.01). Compared with rats fed the control diet, the percentage
      reductions of ACF in rats fed 2.5, 5.0 and 10 g inulin diets/100 g were 25, 51,
      and 65, respectively. The results of this study indicate that mature rats can be
      used as models in ACF studies, and dietary long-chain inulin dose-dependently
      suppresses AOM-induced ACF formation in Fisher 344 mature male rats.

PMID- 12221250
TI  - Dietary inulin suppresses azoxymethane-induced aberrant crypt foci and colon
      tumors at the promotion stage in young Fisher 344 rats.
AB  - This study was designed to determine the effect of 10% dietary long-chain inulin
      on the azoxymethane (AOM)-induced colonic preneoplastic aberrant crypt foci (ACF)
      and small intestinal and colon tumors at the initiation (I), promotion (P) and I
      + P stages (20 rats per treatment) in Fisher 344 male weanling rats. After an
      acclimatization period of 1 wk, groups of Fisher 344 male weanling rats were
      assigned to consume AIN 93G diet (control) or AIN 93G diet containing 10% inulin.
      All the rats received 16 mg/kg body AOM dissolved in saline subcutaneously at 7
      wk of age followed by a second injection at 8 wk of age. An additional group of
      five rats received only saline and consumed the control diet. The rats received
      the assigned diets until asphyxiation by CO(2) at 16 wk of age for the ACF
      experiment and 45 wk for the end-point tumor experiment. Feed intake, weight
      gain, diarrheal index, cecal weight, cecal pH, ACF and tumors in the colon were
      determined. Rats fed inulin had diarrhea after 2 wk of feeding and recovered by
      approximately 4 wk. Cecal weight was greater in rats fed inulin and cecal pH was
      lower. The inulin group had more than 66% fewer aberrant crypts and 60% fewer ACF
      compared with the control group. Tumor incidences in the small intestine and
      colon of rats in the control, I, P and I + P groups were: 78, 31, 0 and 11% and
      90, 73, 69 and 50%, respectively. The corresponding values for the distal portion
      of the colon were 87, 63, 45 and 33%, respectively. Colon tumors per tumor
      bearing rat were 4.2, 3.09, 1.36 and 1.2 for the control, I, P and I + P groups,
      respectively. All groups differed, P < 0.05. The results of this study indicate
      that dietary long-chain inulin suppresses AOM-induced ACF formation, an early
      preneoplastic marker of colon tumorigenesis in rats, and colon tumors,
      particularly at the promotion stage.

PMID- 12221251
TI  - Red wine polyphenols inhibit the growth of colon carcinoma cells and modulate the
      activation pattern of mitogen-activated protein kinases.
AB  - Red wine is a rich source of polyphenols, which exhibit a number of biological
      effects in different in vitro and in vivo systems. The bioavailability of
      polyphenols is poor and the plasma concentrations of major red wine polyphenols
      are usually low after consumption of dietary relevant amounts of red wine. In
      contrast to most organ systems, the gastrointestinal tract (particularly the
      epithelial cells of this organ system) is exposed to high concentrations of
      polyphenols. Here, we show that the total polyphenol pool isolated from a red
      wine (varity Lemberger, vintage 1998) at micromolar concentrations inhibited the
      proliferation of transformed colon epithelial cells HT 29 clone 19A induced by
      epidermal growth factor (EGF). Inhibition of proliferation was also associated
      with modulation of activation of mitogen-activated protein kinases (MAPK). Stress
      activated c-Jun N-terminal kinases 1/2 (JNK) and p38 MAPK were significantly
      activated by red wine polyphenols (6 mmol/L). Maximum phosphorylation of both
      MAPK was observed after a 1-h treatment with red wine polyphenols. In contrast,
      activation of extracellular signal regulated kinase (ERK) 1/2 by EGF (1 nmol/L)
      was significantly inhibited by red wine polyphenols (6 mmol/L). This signaling
      pattern, activation of JNK 1/2 and p38 MAPK and inhibition of ERK 1/2, is typical
      for antiproliferative compounds, indicating that red wine polyphenols may inhibit
      the proliferation of colon carcinoma cells by modulating MAPK intracellular
      signal transduction pathways.

PMID- 12221252
TI  - Up-regulation of nitrogen catabolic enzymes is not required to readily oxidize
      excess protein in cats.

PMID- 12221254
TI  - Quercetin-3-glucoside is transported by the glucose carrier SGLT1 across the
      brush border membrane of rat small intestine.

PMID- 12221259
TI  - Assessment and control of vitamin A deficiency: the Annecy Accords.
AB  - Comprehensive recommendations for the assessment and control of vitamin A
      deficiency (VAD) were rigorously reviewed and revised by a working group and
      presented for discussion at the XX International Vitamin A Consultative Group
      meeting in Hanoi, Vietnam. These recommendations include standardized definitions
      of VAD and VAD disorders. VAD is defined as liver stores below 20 micro g (0.07
      micro mol) of retinol per gram. VAD disorders are defined as any health and
      physiologic consequences attributable to VAD, whether clinically evident
      (xerophthalmia, anemia, growth retardation, increased infectious morbidity and
      mortality) or not (impaired iron mobilization, disturbed cellular differentiation
      and depressed immune response). An estimated 140 million preschool-aged children
      and at least 7.2 million pregnant women are vitamin A deficient, of whom >10
      million suffer clinical complications, principally xerophthalmia but also
      increased mortality, each year. A maternal history of night blindness during a
      recent pregnancy was added to the clinical criteria for assessing vitamin A
      status of a population, and the serum retinol criterion for a "public health
      problem" was revised to 15% or more of children sampled having levels of <20
      micro g/dL (0.7 micro mol/L). Clinical trials and kinetic models indicate that
      young children in developing countries cannot achieve normal vitamin A status
      from plant diets alone. Fortification, supplementation, or other means of
      increasing vitamin A intake are needed to correct widespread deficiency. To
      improve the status of young infants, the vitamin A supplements provided to
      mothers during their first 6 wk postpartum and to young infants during their
      first 6 mo of life should be doubled.

PMID- 12221261
TI  - History of the International Vitamin A Consultative Group 1975-2000.
AB  - The International Vitamin A Consultative Group (IVACG) was established in May
      1975. Since then, IVACG has actively led the campaign against vitamin A
      deficiency disorders (VADD). It operates through a network of policy makers,
      program administrators, and scientists interested in resolving the problem of
      VADD. Through its international meetings, IVACG provides a forum to exchange new
      ideas, to discuss research findings and their policy implications, and share
      experiences with program interventions. It provides technical guidance through
      state-of-the-art publications on VADD. More than 30 technical references have
      been developed. IVACG collaborates with international organizations in developing
      and establishing policy guidelines for diagnosis, treatment, and prevention of
      VADD. During its 25 years, IVACG has given careful consideration to the role of
      vitamin A in infections, morbidity and mortality; assessment methods for use in
      the field and laboratory; other micronutrients and their interaction with vitamin
      A; bioavailability of vitamin A in foods; various interventions including
      supplementation, fortification and dietary diversification; the link between
      science and action; and sustainable control of VADD. IVACG is recognized as a
      credible source and galvanizing force in the field. It should continue to
      identify important research and policy issues and provide policy recommendations
      upon which others can act. Greater emphasis should be placed on integrated and
      multisectoral strategies, taking into account a community's overall needs for
      social, economic, and ecologic development.

PMID- 12221262
TI  - Extent of vitamin A deficiency among preschool children and women of reproductive
      age.
AB  - Knowledge of the extent of vitamin A (VA) deficiency (D) is critical for
      identifying high-risk populations and mobilizing resources for prevention. Yet,
      all estimates are necessarily imperfect, often based on assumptions in the
      absence of data. In 1995, the World Health Organization estimated 254 million
      children to be VA-deficient and 2.8 million to have xerophthalmia. Subsequently,
      estimates were changed to 75-140 million and 3.3 million, respectively. Although
      both sets are consistent with a problem of enormous magnitude, the discrepancies
      also created uncertainty. The present analysis indicates there are approximately
      127 million and 4.4 million preschool children with VAD (serum retinol < 0.70
      micro mol/L or displaying abnormal impression cytology) and xerophthalmia,
      respectively. More than 7.2 million pregnant women in the developing world are VA
      deficient (serum or breast-milk vitamin A concentrations < 0.70 micro mol/L), and
      another 13.5 million have low VA status (0.70-1.05 micro mol/L); >6 million women
      develop night blindness (XN) during pregnancy annually. Roughly 45% of VA
      deficient and xerophthalmic children and pregnant women with low-to-deficient VA
      status live in South and Southeast Asia. These regions harbor >60% of all cases
      of maternal XN, three fourths of whom seem to live in India. Africa accounts for
      25-35% of the global cases of child and maternal VAD; about 10% of all deficient
      persons live in the eastern Mediterranean region, 5-15% live in the Western
      Pacific and approximately 5% live in the Region of the Americas. VA prophylaxis
      seems to be preventing the number of deficient preschool children from increasing
      while probably reducing rates of blindness and mortality. Greater effort is
      needed to assess and prevent VAD and its disorders, particularly among pregnant
      and lactating women.

PMID- 12221263
TI  - Why do children become vitamin A deficient?
AB  - Vitamin A deficiency is very prevalent and contributes substantially to morbidity
      and mortality among young children in developing countries. We identify and
      quantify three causes of vitamin A deficiency in young children based on data
      available in the literature: maternal vitamin A deficiency resulting in low
      concentrations of vitamin A in breast milk, inadequate dietary intake of vitamin
      A during and after weaning and prevalent illness. We developed a set of recursive
      equations to estimate the amount of vitamin A in the liver as a function of age
      over the first 2 y of life. To apply the equations, we selected a best estimate
      value for each input parameter as the most representative of a typical child in a
      developing country. Because of the great variability that exists for each
      variable, we also carried out sensitivity analyses, substituting more extreme
      values for input parameters. We then estimated stores, assuming a child in a
      developing country also receives the newly revised vitamin A supplementation
      regimen recommended by the World Health Organization. Without supplementation, a
      typical child in a developing country is not able to attain and maintain
      "minimally adequate" liver vitamin A stores. To overcome this deficit by eating
      fruits and vegetables alone, the child would need to increase portion sizes about
      10-fold. If the child receives the new supplementation regimen, his or her liver
      stores will still be far short of the average American child (i.e., exceedingly
      far from toxic levels). However, our estimates indicate that the new
      supplementation regimen will permit a typical child in a developing country
      setting to attain minimally adequate vitamin A stores during the first 2 y of
      life.

PMID- 12221264
TI  - Use of under-five mortality rate as an indicator for vitamin A deficiency in a
      population.
AB  - Vitamin A deficiency (VAD) is an important problem in many developing countries.
      If population data are unavailable or outdated for common indicators of VAD, a
      surrogate indicator may suggest whether a problem is likely and full-scale
      assessment is necessary. The Global Vitamin A Initiative report suggests that the
      under-five mortality rate (U5MR) might serve that purpose; a U5MR >70 indicates
      that VAD of public health importance is likely. Should the U5MR be used as a
      surrogate indicator? If so, is 70 the appropriate cutoff? U5MR data were
      collected for countries where the United Nations Children's Fund supports
      programs, along with unpublished vitamin A survey data from the World Health
      Organization. U5MR distribution was compared in countries with and without VAD.
      Sensitivity and specificity using U5MR cutoffs of 70 and 50 were calculated and
      compared with the presence of VAD as proven by a survey. Countries with a U5MR
      >40 have a VAD problem, about 70% of countries with a U5MR between 20 and 50 have
      VAD, and about 25% of countries with a rate <20 still have VAD. With a cutoff of
      50, the U5MR relates well to the existence of a VAD problem in regions where
      malnutrition problems are most prominent. Decreasing the cutoff from 70 to 50
      increased the sensitivity of the criterion and included nine additional deficient
      countries. A cutoff of 40 would increase sensitivity but would include countries
      with localized rather than nationwide problems. It is proposed that a country
      with a U5MR >50 likely has a VAD problem that requires immediate or continuing
      action. These actions include proper, formal assessment of the vitamin A status
      of the population, vitamin A capsule distribution and other program actions.
      Countries with a U5MR between 20 and 50 should assume they have a VAD public
      health problem until surveys prove otherwise.

PMID- 12221265
TI  - Recommendations for indicators: night blindness during pregnancy--a simple tool
      to assess vitamin A deficiency in a population.
AB  - Night blindness during pregnancy caused by vitamin A deficiency is associated
      with an increased risk of morbidity and mortality among women. Because a history
      of maternal night blindness is simple and reliable to use, it is recommended as a
      population-based indicator of vitamin A deficiency. Furthermore, a maternal night
      blindness prevalence of >/=5% is recommended as a cut-off at which vitamin A
      deficiency may be considered to be a problem of public health significance within
      the community. This paper provides the justification for these recommendations.
      Night blindness during pregnancy is strongly associated with low serum and breast
      milk vitamin A concentration, abnormal conjunctival impression cytology and
      impaired dark adaptation, which suggests that it is a valid indicator of vitamin
      A deficiency. The prevalence of night blindness during pregnancy tends to be high
      in countries where the prevalence of xerophthalmia in children is high and in
      countries where interventions are in place to reduce childhood vitamin A
      deficiency. Existing data suggest that misclassification of self-reported
      maternal night blindness may account for a prevalence of up to 3%. The suggested
      cut-off, 5%, is set higher than this potential level of false-positive prevalence
      (3%). Illustrative data from India and Cambodia on childhood xerophthalmia and
      maternal night blindness rates are used to demonstrate the validity of using a 5%
      prevalence of maternal night blindness as indicative of a community vitamin A
      deficiency problem. Finally, it is recommended that night blindness history be
      elicited for a previous pregnancy that ended in a live birth in the past 3 y,
      using the local term for night blindness whenever possible.

PMID- 12221266
TI  - Physiologic indicators of vitamin A status.
AB  - Physiologic indicators reflect the functional consequences of vitamin A
      deficiency and may be particularly useful for detecting early perturbations in
      vitamin A status. In conjunctival impression cytology (CIC), epithelial
      morphology and the presence or absence of mucin spots and goblet cells allow
      samples, obtained by applying filter paper to the temporal conjunctiva, to be
      characterized as normal or typical of vitamin A-deficient keratinizing
      metaplasia. The validity of CIC has been established with reference to other
      indicators of vitamin A status, and a prevalence of > or =20% abnormal results
      has been suggested as indicative of a public health problem. However,
      interpretation of specimens requires considerable training, and nonresponsiveness
      to supplementation is a frequent problem, which limits the utility of CIC as a
      method for evaluating the impact of intervention programs. Several simplified
      field protocols for dark adaptation have been developed, including one in which
      dark adaptation is assessed by the responsiveness of the pupil to light. Night
      blind subjects have consistently shown abnormal results on this test, and a
      significant response to placebo-controlled dosing has been demonstrated for
      children and pregnant women. Scores have correlated significantly with serum
      retinol and relative dose response. Pupillary dark adaptation testing is
      acceptable to most children as young as 2 y old. Limitations of this technique
      include a time course for recovery after dosing as long as 4-6 wk, a testing time
      of 20 min, and the need for 1-3 d of training. Given its low cost, noninvasive
      nature, and lack of the need to transport samples, pupillary dark adaptation
      offers advantages over other techniques for assessing a population's vitamin A
      status.

PMID- 12221267
TI  - Biochemical indicators of vitamin A deficiency: serum retinol and serum retinol
      binding protein.
AB  - Two biochemical indicators are currently recommended for determining whether
      vitamin A deficiency (VAD) is a public health problem: serum retinol and serum
      retinol-binding protein (RBP). After consideration of 40 data sets and the
      original rationale for previously proposed cut-offs, a cut-off for serum retinol
      concentration was proposed at <0.70 micro mol/L (20 micro g/dL) in > or =15% of
      the sampled population. This cut-off should be applied to a representative group
      of preschool age children (6-71 mo). Because measurement of low serum retinol
      concentrations requires high precision, analysis should be done by HPLC. For
      serum RBP, a cut-off cannot be reliably specified, because available data are too
      few and too variable. However, because serum RBP concentration correlates well
      with serum retinol concentration, it can be used to determine whether VAD is a
      public health problem in those populations for which the relationship between
      serum concentrations of retinol and RBP have been established. More efforts to
      establish a reliable cut-off for RBP is warranted, because analysis, in
      particular radial immunodiffusion (RID), is relatively simple and inexpensive.
      Whereas HPLC and RID analyses must be done in a laboratory, methods are being
      developed for assessing serum retinol and RBP under more remote conditions.

PMID- 12221268
TI  - Recommendations for vitamin A supplementation.
AB  - In all populations where vitamin A deficiency is an important public health
      problem, prophylactic vitamin A supplements should be given to all infants and
      young children (0-59 mo), pregnant women and postpartum women within 6 wk after
      delivery. The efficacy of vitamin A supplementation of young children is one of
      the best-proven, safest and most cost-effective interventions in international
      public health. The International Vitamin A Consultative Group (IVACG) also
      recommends that three 50,000-international unit (IU) doses of vitamin A should be
      given at the same time as infant vaccines during the first 6 mo of life. Recent
      kinetic studies have indicated that this regimen will be safe and is necessary to
      maintain the infant's vitamin A stores, even when the mother is also given
      400,000 IU within the first 6 wk after delivery. IVACG will make a decision on
      whether to recommend prophylactic supplementation of all women of childbearing
      age when the results of two large trials in Ghana and Bangladesh are available.
      Active corneal xerophthalmia is always a medical emergency that should be treated
      with immediate high-dose vitamin A. High-dose vitamin A treatment is also
      recommended for infants and young children with xerophthalmia, severe
      malnutrition or measles. Low-dose vitamin A treatment is recommended for women
      with night blindness and/or Bitot's spots. Given the evidence of the cost
      effectiveness of vitamin A supplementation, it is essential that effective
      vitamin A supplementation programs are made universally available to all
      populations where vitamin A deficiency is an important public health problem.

PMID- 12221269
TI  - Estimating the potential for vitamin A toxicity in women and young children.
AB  - This paper describes usual intakes of vitamin A from diet plus low dose
      supplements, reviews methods for assessing vitamin A toxicity and applies a
      kinetic analysis of vitamin A turnover to estimate the effect of high dose
      supplements on vitamin A liver stores in infants and young children. In the
      United States, the 95th percentile of intake by preschoolers from foods and
      supplements exceeds the tolerable upper level (UL) but is below the no-observed
      adverse-effect level (NOAEL). The 95th percentile of vitamin A intake from foods
      and supplements for nonpregnant, nonlactating women aged 19-30 y also exceeds the
      UL but is below the NOAEL for women of reproductive age. In low income
      populations in developing countries, vitamin A intakes of preschoolers and women
      consuming foods plus low dose supplements can also exceed the UL but are unlikely
      to exceed the NOAEL. There are few data on which to establish thresholds for
      excessive vitamin A intake or vitamin A concentrations in tissues. To assess the
      potential toxicity of the new recommendations (see article by Ross in this issue)
      for high dose vitamin A supplements for infants and children, we used a kinetic
      approach to estimate accumulation of the vitamin in liver. The new
      recommendations are unlikely to result in toxic levels (>300 microg per gram of
      liver) even if high dose supplements are inadvertently given monthly. The kinetic
      analysis also illustrates that a constant supply of vitamin A from breast milk
      (and/or complementary foods) is vital for preventing depletion of liver vitamin A
      stores between high dose supplements.

PMID- 12221270
TI  - Consequences of revised estimates of carotenoid bioefficacy for dietary control
      of vitamin A deficiency in developing countries.
AB  - According to existing recommendations of the Food and Agriculture Organization
      (FAO)/World Health Organization (WHO), the amount of provitamin A in a mixed diet
      having the same vitamin A activity as 1 microg of retinol is 6 microg of beta
      carotene or 12 microg of other provitamin A carotenoids. The efficiency of this
      conversion is referred to as bioefficacy. Recently, using data from healthy
      people in developed countries and based on a two-step process, the U.S. Institute
      of Medicine (IOM) derived new conversion factors. The first step established the
      bioefficacy of beta-carotene in oil at 2 microg having the same vitamin A
      activity as 1 microg of retinol; the second step established the bioavailability
      of beta-carotene in foods relative to that of beta-carotene in oil at 1:6. Thus,
      2 microg of beta-carotene in oil or 12 microg of beta-carotene in mixed foods has
      the same vitamin A activity as 1 microg of retinol. Based on existing FAO food
      balance sheets and the FAO/WHO conversion rates, all populations should be able
      to meet their vitamin A requirements from existing dietary sources. However,
      using the new IOM conversion rates, populations in developing countries could not
      achieve adequacy. Additionally, field studies suggest that, instead of 12 microg,
      21 microg of beta-carotene has the same vitamin A activity as 1 microg of
      retinol, which implies that effective vitamin A intake is even lower. Therefore,
      controlling vitamin A deficiency in developing countries requires not only
      vitamin A supplementation but also food-based approaches, including food
      fortification, and possibly the introduction of new strains of plants with
      enhanced vitamin A activity.

PMID- 12221271
TI  - Food fortification to reduce vitamin A deficiency: International Vitamin A
      Consultative Group recommendations.
AB  - In developed countries, food fortification has proven an effective and low-cost
      way to increase the micronutrient supply and reduce the consequences of
      micronutrient deficiencies. It has been rarely used in the developing world, but
      general conclusions can be drawn. The biological efficacy, but not the
      effectiveness, of fortifying oil and hydrogenated oil products as well as cereal
      flours and meals with vitamin A has been shown. Sugar has been fortified with
      vitamin A in Central American countries for years, and biological efficacy and
      program effectiveness are well established. Efficacy of fortifying monosodium
      glutamate with vitamin A was demonstrated but a program has not been established.
      Fortification with vitamin A in the developing world should satisfy certain
      elements for success. a) A potential food matrix (a food regularly consumed,
      produced by a few centralized factories, without sensorial changes compared with
      the nonfortified equivalent, and nutrient remains bioavailable and in a
      sufficient amount) is required. b) Fortified foods should provide at least 15% of
      the recommended daily intakes for the target group (e.g., individuals consuming
      the lowest amount of the fortified food). c) Voluntary fortification of processed
      foods should be regulated to prevent excessive consumption of vitamin A. d)
      Neighboring countries should harmonize technical standards, facilitate compliance
      and minimize conflicts over global trade laws. e) A practical monitoring system
      should be instituted. f) Social marketing activities should be permanent and
      aimed at industry, government and consumers. g) Food fortification should be
      combined with other strategies (e.g., supplementation) to reach those not
      adequately covered by fortification alone. Infants and small children, whose
      dietary habits differ from those of adults, require special attention.
      Fortification of food commodities is a very attractive and economic way to
      prevent and control vitamin A deficiency. Effective food fortification might make
      supplementation of postpartum women and older children unnecessary.

PMID- 12221272
TI  - Process indicators for monitoring and evaluating vitamin A programs.
AB  - Vitamin A deficiency disorders (VADD) are a major public health problem in many
      parts of the world and one of the leading underlying causes of childhood
      mortality. Therefore, VADD control programs can contribute to reaching the
      international development goal of reducing childhood mortality by two thirds by
      the year 2015. Although economic development leads to greater food consumption of
      animal products (the most bioavailable source of vitamin A), other strategies,
      such as high dose vitamin A capsule supplementation, fortification and food
      production programs have been developed to tackle the VADD problem independent of
      economic development efforts. In this article, we discuss the essential role of
      process indicators in monitoring and fine-tuning VADD control and prevention
      programs toward ensuring that such programs will be more effective and cost
      effective.

PMID- 12221273
TI  - Recommendations for monitoring and evaluating vitamin A programs: outcome
      indicators.
AB  - Monitoring and evaluation are essential components of vitamin A intervention
      programs. They enable program managers to track progress in achieving their
      goals. Recommendations for outcome indicators are based on suggestions from the
      International Vitamin A Consultative Group Meeting (IVACG) workshop in late
      October 2000 in Annecy, France, followed by a pre-XX IVACG meeting in Hanoi,
      Vietnam. In areas with detectable xerophthalmia or eye signs, a fall in the
      prevalence of Bitot's spots to <0.5% and a decrease in night blindness during
      pregnancy to <5% indicates that vitamin A deficiency (VAD) is no longer a public
      health problem, although it still may be responsible for excess morbidity and
      mortality. Pupillary dark adaptation has been proposed as an objective indicator
      of vitamin A status. A program is considered to have made progress when the mean
      pupillary threshold improves to better than -1.24 log cd/m(2). For biochemical
      indices, the shift of mean or median values or the frequency distribution of
      preschool children with serum retinol concentration below 0.70 micromol (20
      microg/dL), lactating mothers with breast milk retinol values below 0.70 micromol
      (6 microg per g of milk fat) or below 1.05 micromol (8 microg per g of milk fat)
      are useful to monitor program progress.

PMID- 12221274
TI  - Crop genetic improvement for enhanced human nutrition.
AB  - In the past decade, micronutrient malnutrition has been identified as a major
      underlying cause of numerous human health problems in developing countries. The
      international agricultural research system has been highly successful in
      producing crop varieties with traits desired by farmers, such as higher yield and
      greater tolerance of poor growing conditions. These improved varieties have
      spread widely throughout developing countries and now provide the staple foods
      eaten daily by billions of people, including the poor in many difficult to reach
      rural areas. Modern plant breeding and biotechnology offer new opportunities to
      use this same international system to increase the micronutrient content and
      enhance the nutritional value of these staple foods. Over time, this could be an
      important complement to the progress that is being made in providing
      micronutrient supplements and fortified foods and in encouraging people to eat
      more diversified diets. Nutritionists and agriculturists will need to work
      together to define the deficiencies, target the right populations and deliver the
      right products.

PMID- 12221275
TI  - Assessment and control of vitamin A deficiency disorders.
AB  - The XX International Vitamin A Consultative Group (IVACG) meeting in Hanoi,
      Vietnam, in February 2001 celebrated 25 y of progress in prevention and control
      of vitamin A deficiency disorders (VADD). Programmatic themes included the
      following: 1) intervention innovations, 2) integration of vitamin A
      interventions, 3) the increased risk to health of women who are deficient, 4)
      measurement of progress and impact and 5) programmatic sustainability. The
      history of IVACG was remembered and the growth of the group from a meeting of 30
      to 40 persons in 1975 to nearly 600 delegates from 63 countries was described.
      Successful adaptation to new challenges and scientific advances, in moving
      science to practice, was noted. Guidelines for indicators and interventions were
      reviewed. A set of revised recommendations were made, including the following
      indicators for assessment (and, for some, outcome evaluation) of VADD: 1) under
      five mortality rate >50 as a surrogate indicator to trigger action, 2) maternal
      night blindness >5%, 3) rapid dark adaptation worse than -1.11 log cd/m(2) and 4)
      serum retinol <0.7 micro mol/L (>15%) in young children (<6 y). Key
      recommendations for specific interventions were to double the existing dose of
      prophylactic vitamin A supplementation to 50,000 international units (IU) at the
      three Expanded Programme on Immunization contacts for young infants (<6 mo) and
      to two doses of 200,000 IU each for women within 6 wk after delivery; to support
      fortification as a valid and necessary strategy to combat VADD; and to recognize
      that food-based approaches should include promoting breast-feeding and consuming
      animal products, because promoting plant-based foods alone will not eliminate
      VADD in young children due to the low bioefficacy of dietary beta-carotene. This
      meeting clearly set the agenda for the twenty-first century and called for
      successful implementation of integrated approaches that will eliminate VADD.

PMID- 12221276
TI  - 25 Years of progress in controlling vitamin A deficiency: looking to the future.
      Proceedings and abstracts of the XX International Vitamin A Consultative Group
      Meeting. Hanoi, Vietnam, 12-15 February 2001.

PMID- 12221279
TI  - Nerve growth factor controls GAP-43 mRNA stability via the phosphoprotein ARPP
      19.
AB  - The membrane phosphoprotein GAP-43 is involved in axon growth and synaptic
      plasticity. In PC12 pheochromocytoma cells, induction of a neuronal phenotype by
      nerve growth factor (NGF) is accompanied by a marked increase in GAP-43 levels.
      NGF regulates GAP-43 expression by altering the half-life of its mRNA. We report
      here that the phosphoprotein ARPP-19 mediates this regulation. In an NGF
      dependent manner, ARPP-19 bound to a region in the 3' end of GAP-43 mRNA
      previously found to be important for regulating the half-life of the mRNA.
      Overexpression of wild-type ARPP-19 in PC12 cells increased the NGF-dependent
      expression of a reporter construct linked to the critical 3' region of GAP-43
      mRNA. Mutation of serine 104, the site of phosphorylation by protein kinase A in
      ARPP-19, to either alanine or aspartate abolished this regulation in PC12 cells.
      These findings demonstrate that ARPP-19 is an important link between NGF
      signaling and post-transcriptional control of neuronal gene expression.

PMID- 12221280
TI  - Inhibition of hypochlorous acid-induced cellular toxicity by nitrite.
AB  - Chronic inflammation results in increased nitrogen monoxide (.NO) formation and
      the accumulation of nitrite (NO(2-)). Neutrophils stimulated by various
      inflammatory mediators release myeloperoxidase to produce the cytotoxic agent
      hypochlorous acid (HOCl). Exposure of chondrocytic SW1353 cells to HOCl resulted
      in a concentration- and time-dependent loss in viability, ATP, and glutathione
      levels. Treatment of cells with NO(2-) but not nitrate (NO(3-)) substantially
      decreased HOCl-dependent cellular toxicity even when NO(2-) was added at low
      (microM) concentrations. In contrast, NO(2-) alone (even at 1 mM concentrations)
      did not affect cell viability or ATP and glutathione levels. These data suggest
      that NO(2-) accumulation at chronic inflammatory sites, where both HOCl and.NO
      are overproduced, may be cytoprotective against damage caused by HOCl. We propose
      that this is because HOCl is removed by reacting with NO(2-) to give nitryl
      chloride (NO2Cl), which is less damaging in our cell system.

PMID- 12221281
TI  - Tumor necrosis factor-alpha regulation of CD4+CD25+ T cell levels in NOD mice.
AB  - The mechanism by which tumor necrosis factor-alpha (TNF) differentially modulates
      type I diabetes mellitus in the nonobese diabetic (NOD) mouse is not well
      understood. CD4+CD25+ T cells have been implicated as mediators of self
      tolerance. We show (i) NOD mice have a relative deficiency of CD4+CD25+ T cells
      in thymus and spleen; (ii) administration of TNF or anti-TNF to NOD mice can
      modulate levels of this population consistent with their observed differential
      age-dependent effects on diabetes in the NOD mouse; (iii) CD4+CD25+ T cells from
      NOD mice treated neonatally with TNF show compromised effector function in a
      transfer system, whereas those treated neonatally with anti-TNF show no
      alteration in ability to prevent diabetes; and (iv) repeated injection of
      CD4+CD25+ T cells into neonatal NOD mice delays diabetes onset for as long as
      supplementation occurred. These data suggest that alterations in the number and
      function of CD4+CD25+ T cells may be one mechanism by which TNF and anti-TNF
      modulate type I diabetes mellitus in NOD mice.

PMID- 12221282
TI  - Crystal structure of DhbE, an archetype for aryl acid activating domains of
      modular nonribosomal peptide synthetases.
AB  - The synthesis of the catecholic siderophore bacillibactin is accomplished by the
      nonribosomal peptide synthetase (NRPS) encoded by the dhb operon. DhbE is
      responsible for the initial step in bacillibactin synthesis, the activation of
      the aryl acid 2,3-dihydroxybenzoate (DHB). The stand-alone adenylation (A) domain
      DhbE, the structure of which is presented here, exhibits greatest homology to
      other NRPS A-domains, acyl-CoA ligases and luciferases. It's structure is solved
      in three different states, without the ligands ATP and DHB (native state), with
      the product DHB-AMP (adenylate state) and with the hydrolyzed product AMP and DHB
      (hydrolyzed state). The 59.9-kDa protein folds into two domains, with the active
      site at the interface between them. In contrast to previous proposals of a major
      reorientation of the large and small domains on substrate binding, we observe
      only local structural rearrangements. The structure of the phosphate binding loop
      could be determined, a motif common to many adenylate-forming enzymes, as well as
      with bound DHB-adenylate and the hydrolyzed product DHB*AMP. Based on the
      structure and amino acid sequence alignments, an adapted specificity conferring
      code for aryl acid activating domains is proposed, allowing assignment of
      substrate specificity to gene products of previously unknown function.

PMID- 12221283
TI  - A p5 integration efficiency element mediates Rep-dependent integration into AAVS1
      at chromosome 19.
AB  - Adeno-associated virus (AAV) undergoes site-specific integration into human
      chromosome 19 through a deletion-substitution mechanism at the well characterized
      AAVS1 site. We have shown previously that a cis element within the left end of
      the AAV genome enhances the efficiency of Rep-mediated site-specific integration
      into chromosome 19 when present in inverted terminal repeat-containing
      recombinant AAV (rAAV) plasmids. We now demonstrate that a 138-bp cis element,
      the p5 integration efficiency element (p5IEE), mediates efficient integration.
      The p5IEE is not only required for efficient site-specific integration, it is
      also sufficient. Integration mediated by the p5IEE occurs in the absence of the
      AAV inverted terminal-repeat elements. The data presented in this study
      demonstrate that the p5IEE is a multifunctional element, serving as the highly
      regulatable Rep promoter and the primary substrate for targeted integration.

PMID- 12221284
TI  - Convergent evolution sheds light on the anti-beta -elimination mechanism common
      to family 1 and 10 polysaccharide lyases.
AB  - Enzyme-catalyzed beta-elimination of sugar uronic acids, exemplified by the
      degradation of plant cell wall pectins, plays an important role in a wide
      spectrum of biological processes ranging from the recycling of plant biomass
      through to pathogen virulence. The three-dimensional crystal structure of the
      catalytic module of a "family PL-10" polysaccharide lyase, Pel10Acm from
      Cellvibrio japonicus, solved at a resolution of 1.3 A, reveals a new
      polysaccharide lyase fold and is the first example of a polygalacturonic acid
      lyase that does not exhibit the "parallel beta-helix" topology. The "Michaelis"
      complex of an inactive mutant in association with the substrate
      trigalacturonate/Ca2+ reveals the catalytic machinery harnessed by this
      polygalacturonate lyase, which displays a stunning resemblance, presumably
      through convergent evolution, to the tetragalacturonic acid complex observed for
      a structurally unrelated polygalacturonate lyase from family PL-1. Common
      coordination of the -1 and +1 subsite saccharide carboxylate groups by a protein
      liganded Ca2+ ion, the positioning of an arginine catalytic base in close
      proximity to the alpha-carbon hydrogen and numerous other conserved enzyme
      substrate interactions, considered in light of mutagenesis data for both
      families, suggest a generic polysaccharide anti-beta-elimination mechanism.

PMID- 12221285
TI  - A conserved mechanism for extracellular signaling in eukaryotes and prokaryotes.
AB  - Epidermal growth factor receptor (EGFr) is a key mediator of cell communication
      during animal development and homeostasis. In Drosophila, the signaling event is
      commonly regulated by the polytopic membrane protein Rhomboid (RHO), which
      mediates the proteolytic activation of EGFr ligands, allowing the secretion of
      the active signal. Until very recently, the biochemical function of RHO had
      remained elusive. It is now believed that Drosophila RHO is the founder member of
      a previously undescribed family of serine proteases, and that it could be
      directly responsible for the unusual, intramembranous cleavage of EGFr ligands.
      Here we show that the function of RHO is conserved in Gram-negative bacteria.
      AarA, a Providencia stuartii RHO-related protein, is active in Drosophila on the
      fly EGFr ligands. Vice versa, Drosophila RHO-1 can effectively rescue the
      bacterium's ability to produce or release the signal that activates density
      dependent gene regulation (or quorum sensing). This study provides the first
      evidence that prokaryotic and eukaryotic RHOs could have a conserved role in cell
      communication and that their biochemical properties could be more similar than
      previously anticipated.

PMID- 12221286
TI  - Experimental control of pancreatic development and maintenance.
AB  - To investigate the role of the HOX-like homeoprotein PDX1 in the formation and
      maintenance of the pancreas, we have genetically engineered mice so that the only
      source of PDX1 is a transgene that can be controlled by the application of
      tetracycline or its analogue doxycycline. In these mice the coding region for the
      tetracycline-regulated transactivator (tTA(off)) has replaced the coding region
      of the endogenous Pdx1 gene to ensure correct temporal and spatial expression of
      the regulatable transactivator. In the absence of doxycycline, tTA(off) activates
      the transcription of a bicistronic transgene encoding PDX1 and an enhanced green
      fluorescent protein reporter, which acts as a visual marker of transgene
      expression in living cells. Expression of the transgene-encoded PDX1 rescues the
      Pdx1-null phenotype; the pancreata of these mice develop and function normally.
      The rescue is conditional; doxycycline-mediated repression of the transgenic Pdx1
      throughout gestation recapitulates the Pdx1 null phenotype. Moreover, application
      of doxycycline at mid-pancreogenesis blocks further development. Adult animals of
      the rescue genotype that were treated with doxycycline for 3 weeks shut off Pdx1
      expression, decreased insulin production, and lost the ability to maintain
      glucose homeostasis. These results demonstrate the feasibility of controlling the
      formation of an organ during embryogenesis in utero and the maintenance of the
      mature organ through the experimental manipulation of a key developmental
      regulator.

PMID- 12221288
TI  - Transgenic cyclooxygenase-2 overexpression sensitizes mouse skin for
      carcinogenesis.
AB  - Genetic and pharmacological evidence suggests that overexpression of
      cyclooxygenase-2 (COX-2) is critical for epithelial carcinogenesis and provides a
      major target for cancer chemoprevention by nonsteroidal antiinflammatory drugs.
      Transgenic mouse lines with keratin 5 promoter-driven COX-2 overexpression in
      basal epidermal cells exhibit a preneoplastic skin phenotype. As shown here, this
      phenotype depends on the level of COX-2 expression and COX-2-mediated
      prostaglandin accumulation. The transgenics did not develop skin tumors
      spontaneously but did so after a single application of an initiating dose of the
      carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Long-term treatment with the
      tumor promoter phorbol 12-myristate 13-acetate, as required for tumorigenesis in
      wild-type mice, was not necessary for transgenics. The ratios of squamous cell
      carcinomas to papillomas and of sebaceous gland adenomas to papillomas plus
      squamous cell carcinomas were increased markedly in transgenic mice treated with
      DMBA alone compared with DMBA/phorbol 12-myristate 13-acetate-treated transgenic
      and wild-type mice. Thus, COX-2 overexpression, which leads to high levels of
      epidermal prostaglandin E(2), prostaglandin F(2alpha), and 15-deoxy(delta12,14)
      PGJ(2), is insufficient for tumor induction but transforms epidermis into an
      "autopromoted" state, i.e., dramatically sensitizes the tissue for genotoxic
      carcinogens.

PMID- 12221287
TI  - Folate synthesis in plants: the first step of the pterin branch is mediated by a
      unique bimodular GTP cyclohydrolase I.
AB  - GTP cyclohydrolase I (GCHI) mediates the first and committing step of the pterin
      branch of the folate-synthesis pathway. In microorganisms and mammals, GCHI is a
      homodecamer of approximately 26-kDa subunits. Genomic approaches identified
      tomato and Arabidopsis cDNAs specifying approximately 50-kDa proteins containing
      two GCHI-like domains in tandem and indicated that such bimodular proteins occur
      in other plants. Neither domain of these proteins has a full set of the residues
      involved in substrate binding and catalysis in other GCHIs. The tomato and
      Arabidopsis cDNAs nevertheless encode functional enzymes, as shown by
      complementation of a yeast fol2 mutant and by assaying GCHI activity in extracts
      of complemented yeast cells. Neither domain expressed separately had GCHI
      activity. Recombinant tomato GCHI formed dihydroneopterin triphosphate as
      reaction product, as do other GCHIs, but unlike these enzymes it did not show
      cooperative behavior and was inhibited by its substrate. Denaturing gel
      electrophoresis verified that the bimodular GCHI polypeptide is not cleaved in
      vivo into its component domains, and size-exclusion chromatography indicated that
      the active enzyme is a dimer. The deduced tomato and Arabidopsis GCHI
      polypeptides lack overt targeting sequences and thus are presumably cytosolic, in
      contrast to other plant folate-synthesis enzymes, which are mitochondrial
      proteins with typical signal peptides. GCHI mRNA and protein are strongly in
      expressed unripe tomato fruits, implying that fruit folate is made in situ rather
      than imported. As ripening advances, GCHI expression declines sharply, and folate
      content drops, suggesting that folate synthesis fails to keep pace with turnover.

PMID- 12221289
TI  - Ubiquitination of inducible nitric oxide synthase is required for its
      degradation.
AB  - Inducible nitric oxide synthase (iNOS) is responsible for nitric oxide (NO)
      synthesis from l-arginine in response to inflammatory mediators. We have
      previously shown that iNOS is degraded through the 26S proteasome. Targeting of
      proteins for proteasomal degradation may or may not require their covalent
      linkage to multiubiquitin chains (ubiquitination). In addition, ubiquitination of
      a protein can serve functions other than signaling proteolysis. In this context,
      it is not known whether iNOS is subject to ubiquitination or whether
      ubiquitination is required for its degradation. In this study, we show that iNOS,
      expressed in HEK293 cells or induced in primary bronchial epithelial cells, A549
      cells, or murine macrophages, is subject to ubiquitination. To investigate
      whether iNOS ubiquitination is required for its degradation, HEK293T cells were
      cotransfected with plasmids containing cDNAs of human iNOS and of the dominant
      negative ubiquitin mutant K48R. Disruption of ubiquitination by K48R ubiquitin
      resulted in inhibition of iNOS degradation. ts20 is a mutant cell line that
      contains a thermolabile ubiquitin-activating enzyme (E1) that is inactivated at
      elevated temperature, preventing ubiquitination. Incubation of ts20 cells, stably
      expressing human iNOS, at the nonpermissive temperature (40 degrees C) resulted
      in inhibition of iNOS degradation and marked accumulation of iNOS. These studies
      indicate that iNOS is subject to ubiquitination and that ubiquitination is
      required for its degradation.

PMID- 12221290
TI  - Directional selection is the primary cause of phenotypic diversification.
AB  - Selection is widely accepted as the principal force shaping phenotypic variation
      within populations. Its importance in speciation and macroevolution has been
      questioned, however, because phenotypic differences between species or higher
      taxa sometimes appear to be nonadaptive. Here, we use the quantitative trait
      locus (QTL) sign test to evaluate the importance of directional selection in
      phenotypic divergence. If a trait has a history of directional selection, QTL
      effects should be mostly in the same direction; otherwise QTLs with antagonistic
      effects should be common. Analysis of QTL effects for 572 traits from 86 studies
      revealed significantly fewer antagonistic QTLs than expected under neutrality, a
      result that validates Darwin's claim that phenotypic diversification is caused
      mainly by selection. Moreover, interspecific trait differences were more strongly
      or consistently selected than intraspecific differences, strengthening a growing
      consensus among students of speciation that directional selection is the primary
      cause of speciation. Contrary to studies of selection in contemporary
      populations, life history traits appear to be selected more strongly than
      morphological traits, but traits related to the timing of development are weakly
      selected relative to most other traits.

PMID- 12221291
TI  - Crosslinking of membrane-embedded cysteines reveals contact points in the EmrE
      oligomer.
AB  - EmrE is a small multidrug transporter that extrudes various drugs in exchange
      with protons, thereby rendering Escherichia coli cells resistant to these
      compounds. In this study, relative helix packing in the EmrE oligomer solubilized
      in detergent was probed by intermonomer crosslinking analysis. Unique cysteine
      replacements in transmembrane domains were shown to react with organic mercurials
      but not with sulfhydryl reagents, such as maleimides and methanethiosulfonates. A
      new protocol was developed based on the use of HgCl(2), a compound known to react
      rapidly and selectively with sulfhydryl groups. The reaction can bridge vicinal
      pairs of cysteines and form an intermolecular mercury-linked dimer. To circumvent
      problems inherent to mercury chemistry, a second crosslinker, hexamethylene
      diisocyanate, was used. After the HgCl(2) treatment, excess reagent was removed
      and the oligomers were dissociated with a strong denaturant. Only those
      previously crosslinked reacted with hexamethylene diisocyanate. Thus, vicinal
      cysteine-substituted residues in the EmrE oligomer were identified. It was shown
      that transmembrane domain (TM)-1 and TM4 in one subunit are in contact with the
      corresponding TM1 and TM4, respectively, in the other subunit. In addition, TM1
      is also in close proximity to TM4 of the neighboring subunit, suggesting possible
      arrangements in the binding and translocation domain of the EmrE oligomer. This
      method should be useful for other proteins with cysteine residues in a low
      dielectric environment.

PMID- 12221292
TI  - Gbeta gamma -independent constitutive association of Galpha s with SHP-1 and
      angiotensin II receptor AT2 is essential in AT2-mediated ITIM-independent
      activation of SHP-1.
AB  - Conventional mode of activation of SH2 domain-containing phosphatase 1 (SHP-1) by
      a single transmembrane (TM) inhibitory receptor such as killer cell inhibitory
      receptor, Fcgamma receptor type IIb1, and paired Ig-like receptors of inhibitory
      types requires tyrosine phosphorylation of immunoreceptor tyrosine-based
      inhibitory (ITIM) motifs in the cytoplasmic domains of the inhibitory receptors.
      Contrary to this paradigm, AT(2), a G protein-coupled 7TM receptor that does not
      undergo tyrosine phosphorylation in response to angiotensin II (Ang II)
      stimulation, also activates SHP-1. Here we show that SHP-1 constitutively and
      physically associates with AT(2) receptor in transfected COS-7 cells. On
      stimulation by Ang II, SHP-1 becomes activated and dissociated from AT(2)
      receptor, independent of pertussis toxin. Cotransfection of transducin
      G(betagamma) inhibits SHP-1/AT(2) association and the SHP-1 activation, whereas
      cotransfection of C-terminal of beta-adrenergic receptor kinase, which abrogates
      G(betagamma) signaling, facilitates SHP-1 activation. Surprisingly, SHP-1/AT(2)
      association and the SHP-1 activation requires the presence of G(alphas) as shown
      by differential coimmunoprecipitation, dominant negative G(alphas),
      constitutively active G(alphas), and G(alpha) peptides. A mutant AT(2) receptor
      D141A-R142L that is inactive in G(alpha) protein activation constitutively
      associates with SHP-1 and activates it. Together, these results indicate that
      G(alphas) alone, rather than exclusively in the form of G(alphabetagamma)
      heterotrimer may facilitate signal transduction for G protein-coupled receptors,
      suggesting a novel mechanism distinct from the classic paradigm of heterotrimeric
      G proteins. The AT(2)-mediated ITIM-independent activation of SHP-1 that is
      distinct from the conventional mode of activation, may represent a general
      paradigm for activation of SHP-1/2-class tyrosine phosphatases by G protein
      coupled receptors.

PMID- 12221293
TI  - Application of charge density methods to a protein model compound: calculation of
      Coulombic intermolecular interaction energies from the experimental charge
      density.
AB  - A combined experimental and theoretical charge density study of the pentapeptide
      Boc-Gln-d-Iva-Hyp-Ala-Phol (Boc, butoxycarbonyl; Gln, glutamine; Iva, isovaline;
      Hyp, hydroxyproline; Ala, ethylalanine; Phol, phenylalaninol) is described. The
      experimental analysis, based on synchrotron x-ray data collected at 20 K, is
      combined with ab initio theoretical calculations. The topologies of the
      experimental and theoretical densities are analyzed in terms of the atoms in
      molecules quantum theory. Topological parameters, including atomic charges and
      higher moments integrated over the atomic basins, have been evaluated with the
      program topxd and are used to calculate the electrostatic interactions between
      the molecules in the crystal. The interaction energies obtained after adding
      dispersive and repulsive van der Waals contributions agree quite well with those
      based on M-B3LYP/6-31G** dimer calculations for two of the three dimers in the
      crystal, whereas for the third a larger stabilization is obtained than predicted
      by the calculation. The agreement with theory is significantly better than that
      obtained with multipole moments derived directly from the aspherical atom
      refinement. The convergence of the interaction as a function of addition of
      successively higher moments up to and including hexadecapoles (l = 4) is found to
      be within 2-3 kJ/mol. Although shortcomings of both the theoretical and
      experimental procedures are pointed out, the agreement obtained supports the
      potential of the experimental method for the evaluation of interactions in larger
      biologically relevant molecules.

PMID- 12221294
TI  - The ribosome filter hypothesis.
AB  - A variety of posttranscriptional mechanisms affects the processing, subcellular
      localization, and translation of messenger RNAs (mRNAs). Translational control
      appears to occur primarily at the initiation rather than the elongation stage. It
      has been suggested that translation is mediated largely by means of a cap
      binding/scanning mechanism. On the basis of recent findings, we propose here that
      differential binding of particular mRNAs to eukaryotic 40S ribosomal subunits
      before translation may also selectively affect rates of polypeptide chain
      production. In this view, ribosomal subunits themselves are considered to be
      regulatory elements or filters that mediate interactions between particular mRNAs
      and components of the translation machinery. Differences in these interactions
      affect how efficiently individual mRNAs compete for ribosomal subunits. These
      competitive interactions would depend in part on the complementarity between
      sequences in mRNA and rRNA, as well as on structural differences among ribosomes
      in different cell types. By these means, translation may either be enhanced
      through increased recruitment of ribosomes or inhibited through strong
      interactions that sequester mRNAs. We propose that ribosomal filters may be
      important in cell differentiation and describe experimental tests for the filter
      hypothesis.

PMID- 12221295
TI  - Inhibition of Fe-S cluster biosynthesis decreases mitochondrial iron export:
      evidence that Yfh1p affects Fe-S cluster synthesis.
AB  - Decreased expression of Yfh1p in the budding yeast, Saccharomyces cerevisiae, and
      the orthologous human gene frataxin results in respiratory deficiency and
      mitochondrial iron accumulation. The absence of Yfh1p decreases mitochondrial
      iron export. We demonstrate that decreased expression of Nfs1p, the yeast
      cysteine desulfurase that plays a central role in Fe-S cluster synthesis, also
      results in mitochondrial iron accumulation due to decreased export of
      mitochondrial iron. In the absence of Yfh1p, activity of Fe-S-containing enzymes
      (aconitase, succinate dehydrogenase) is decreased, whereas the activity of a non
      Fe-S-containing enzyme (malate dehydrogenase) is unaffected. Aconitase protein
      was abundant even though the activity of aconitase was decreased in both aerobic
      and anaerobic conditions. These results demonstrate a direct role of Yfh1p in the
      formation of Fe-S clusters and indicate that mitochondrial iron export requires
      Fe-S cluster biosynthesis.

PMID- 12221296
TI  - Type IA DNA topoisomerases: strictly one step at a time.

PMID- 12221297
TI  - Photosynthate allocations in rice plants: food production or atmospheric methane?

PMID- 12221298
TI  - The genomics of symbiosis: hosts keep the baby and the bath water.

PMID- 12221299
TI  - The WHO draft manual perpetuates barriers to care.

PMID- 12221302
TI  - Use of psychotropic drugs by mentally ill Medicaid beneficiaries.

PMID- 12221301
TI  - A service response to prolonged recovery in early psychosis.

PMID- 12221303
TI  - Healing through social and spiritual affiliation.

PMID- 12221304
TI  - Emergency pharmacological management of aggression among agitated psychotic
      patients in Japan.

PMID- 12221305
TI  - Innovative use of virtual reality technology in the treatment of PTSD in the
      aftermath of September 11.

PMID- 12221306
TI  - An analysis of the definitions of mental illness used in state parity laws.
AB  - OBJECTIVE: Thirty-four states have enacte mental health parity laws that require
      a health plan, insurer, or employer to provide coverage for mental illness equal
      to that for physical illness. This study analyzed definitions of mental illness
      used in state parity laws, identified factors influencing the development of
      these definitions, and examined the effects of different definitions on access to
      care for persons with mental illness. METHODS: Specific language in each state's
      parity legislation was analyzed. Interviews were conducted with policy makers,
      mental health providers, advocates, and insurers to determine factors influencing
      a state's definition. Current definitions of mental illness used in the clinical
      literature and in federal policy were reviewed and compared with definitions used
      in state parity laws. RESULTS: The definitions of mental illness used in state
      parity legislation vary significantly and fall into one of three major
      categories: "broad-based mental illness," "serious mental illness," or
      "biologically based mental illness." To define each of these categories, state
      legislatures do not rely on clinically accepted definitions or federal mental
      health policy. Rather, influenced by political and economic factors, they are
      developing their own definitions. CONCLUSIONS: Definitions of mental illness in
      state parity laws have important implications for access, cost, and
      reimbursement; they determine which populations receive a higher level of mental
      health services. Future research must qualitatively examine how state definitions
      affect the use and cost of mental health services.

PMID- 12221307
TI  - Use of complementary and alternative medicine for symptoms of attention-deficit
      hyperactivity disorder.
AB  - OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is a common childhood
      psychiatric condition for which evidence-based treatments have been established.
      This study describes use of complementary and alternative medicine among children
      with ADHD or at risk of having ADHD and explores possible predictors of use of
      such treatments. METHODS: A sample of 1,615 parents of elementary school students
      in a public school district were interviewed in a telephone screening survey of
      ADHD symptoms and use of traditional and nontraditional ADHD treatment. A total
      of 822 parents had a child with a diagnosis of ADHD, had a child in whom ADHD was
      suspected, or had a child about whose emotions or behavior the parents or school
      staff had general concerns. RESULTS: Use of complementary and alternative
      medicine was significantly higher among children who had received a diagnosis of
      ADHD (12 percent) or in whom ADHD was suspected (7 percent) than among those
      about whom parents or school staff had general concerns (3 percent). Faith
      healing had been used for 4 percent of the 822 children. Nontraditional
      treatments were more likely to have been used among children with a diagnosis or
      a suspected diagnosis of ADHD and those whose parents used the Internet as a
      source of information than among other children. CONCLUSIONS: Providers should
      inquire about nontraditional interventions and educate families about evidence
      based approaches when treating children with ADHD.

PMID- 12221308
TI  - Correlates of ADHD among children in pediatric and psychiatric clinics.
AB  - OBJECTIVE: Conventional wisdom among pediatricians has been that children with
      attention-deficit hyperactivity disorder (ADHD) who receive their diagnosis and
      are managed in the primary care setting have fewer comorbid psychiatric disorders
      and milder impairments than those seen in psychiatric clinics. The authors sought
      to determine whether comorbidity and clinical correlates of ADHD differ among
      children in these two settings. METHODS: A case-control study design was used.
      Participants were 522 children and adolescents of both sexes, six to 18 years of
      age, with (N=280) and without (N=242) ADHD. Participants were drawn from
      pediatric and psychiatric clinics in a tertiary care hospital and a health
      maintenance organization in a large metropolitan area. Assessments were conducted
      with standardized measures of psychiatric, cognitive, social, academic, and
      family function. RESULTS: The number, type, clusters, and age at onset of ADHD
      symptoms were nearly identical for youths at pediatric and psychiatric
      ascertainment sources. Regardless of source, participants with ADHD were
      significantly more likely than controls to have a higher prevalence of mood
      disorders, other disruptive behavior, anxiety disorders, and substance use
      disorders. Significant impairments of intellectual, academic, interpersonal, and
      family functioning did not differ between ascertainment sources. CONCLUSIONS:
      Children with ADHD from both psychiatric and pediatric practices have
      prototypical symptoms of the disorder; high levels of comorbidity with mood,
      anxiety, and disruptive behavior disorders; and impairments in cognitive,
      interpersonal, and academic function that do not differ by ascertainment source.
      These findings suggest that children cared for in pediatric practice have similar
      levels of comorbidity and dysfunction as psychiatrically referred youth.

PMID- 12221309
TI  - Gambling disorders among homeless persons with substance use disorders seeking
      treatment at a community center.
AB  - OBJECTIVES: Epidemiological research suggests that homelessness is a risk factor
      for elevated levels of psychiatric comorbidity and other health risks. This study
      examined the prevalence of disordered gambling and its association with treatment
      of psychiatric and substance use disorders among a cohort of homeless people
      seeking treatment at a community services program. METHODS: Between 1998 and
      2000, intake workers evaluated the level of gambling disorder among 171
      consecutive homeless persons with substance use disorders who sought treatment at
      the Moving Ahead Program in Boston. Program staff administered the DSM-IV
      subscale of the Massachusetts Gambling Screen at intake. RESULTS: The prevalence
      rates of level 2 and level 3 gambling disorders were 12.8 percent and 5.5
      percent, respectively. These rates are higher than that of the general adult
      population but comparable to those of other patients with substance use disorders
      and psychiatric diagnoses. Program participants with level 3 gambling disorders
      had been homeless more often and at a younger age and had had less substance
      abuse treatment and more psychiatric treatment than participants with level 1 or
      level 2 gambling disorders. Participants with level 2 gambling disorders had been
      homeless more often and for a longer duration than participants without gambling
      disorders. CONCLUSIONS: These findings should encourage clinicians working with
      homeless people to screen for gambling-related problems and disorders.

PMID- 12221310
TI  - Cost-effectiveness of two vocational rehabilitation programs for persons with
      severe mental illness.
AB  - OBJECTIVE: This study sought to determine differences in the cost-effectiveness
      of two vocational programs: individual placement and support (IPS), in which
      employment specialists within a mental health center help patients obtain
      competitive jobs and provide them with ongoing support, and enhanced vocational
      rehabilitation (EVR), in which stepwise services that involve prevocational
      experiences are delivered by rehabilitation agencies. METHODS: A total of 150
      unemployed inner-city patients with severe mental disorders who expressed an
      interest in competitive employment were randomly assigned to IPS or EVR programs
      and were followed for 18 months. Wages from all forms of employment and the
      number of weeks and hours of competitive employment were tracked monthly.
      Estimates were made of direct mental health costs and vocational costs.
      Incremental cost-effectiveness ratios (ICERs) were calculated for competitive
      employment outcomes and total wages. RESULTS: No statistically significant
      differences were found in the overall costs of IPS and EVR. Participation in the
      IPS program was associated with significantly more hours and weeks of competitive
      employment. However, the average combined earnings-earnings from competitive and
      noncompetitive employment-were virtually the same both programs. The ICER
      estimates indicated that participants in the IPS program worked in competitive
      employment settings for an additional week over the 18-month period at a cost of
      $283 ($13 an hour). CONCLUSIONS: The analyses suggest that IPS participants
      engaged in competitive employment at a higher cost. When combined earnings were
      used as the outcome, data from the statistical analyses were insufficient to
      enable any firm conclusions to be drawn. The findings illustrate the importance
      of choice of outcomes in evaluations of employment programs.

PMID- 12221311
TI  - Effects of psychoeducation for Korean Americans with chronic mental illness.
AB  - OBJECTIVE: Korean Americans' access to mental health services may be limited
      because of differences in their views of mental illness compared with Westerners,
      unfamiliarity with treatment methods, and cultural associations of social stigma
      with mental problems. This study used data from an urban outpatient clinic to
      assess the effects of a ten-week psychoeducational intervention for Korean
      Americans with chronic mental illness. METHODS: Forty-eight Korean-American
      adults with a diagnosis of schizophrenia were randomly assigned to either an
      experimental group that provided a culturally sensitive psychoeducational group
      program in addition to individual supportive therapy or a control group that
      offered only individual supportive therapy. The two groups were compared on pre-
      and posttreatment measures of psychiatric symptoms, attitudes about and
      understanding of mental illness, and coping skills. The experimental
      psychoeducational treatment group was expected to show lower symptom severity,
      greater understanding of mental illness leading to a decreased perception of
      stigma, and greater coping skills after the intervention than the control group.
      Comparisons were made with repeated-measures analysis of covariance with the
      effects of gender and education controlled for. RESULTS: Compared with the
      control group, the psychoeducational group showed significantly reduced symptom
      severity and perception of stigma and greater coping skills immediately after
      treatment. CONCLUSIONS: These findings suggest that a culturally sensitive
      psychoeducational intervention is a useful short-term treatment modality for
      Korean Americans with a diagnosis of schizophrenia.

PMID- 12221312
TI  - A pilot study of community mental health care for depression in a supermarket
      setting.
AB  - OBJECTIVE: Women with depression whose diagnosis is made in community mental
      health clinics attend relatively few treatment sessions. A pilot project was
      undertaken to test the feasibility of providing psychotherapy for depressed women
      in a supermarket, a novel setting that may minimize barriers to care such as
      stigma associated with visiting a mental health clinic. METHODS: Twelve women who
      met DSM-IV criteria for a depressive disorder were recruited from a rural mental
      health clinic and offered 16 weekly sessions of supportive psychotherapy with
      cognitive-behavioral elements in an administrative conference room of a local
      supermarket. Outcomes measured were treatment attendance, depressive symptoms,
      and satisfaction with treatment. RESULTS: Six of the women completed the study.
      For the entire group, the mean number of sessions attended was 5.2. Those who
      completed the study attended an average of 8.7 sessions and showed significant
      improvement on measures of depression and anxiety. They rated their treatment
      experience as "very satisfactory." For the two therapists, conducting therapy in
      the supermarket presented some logistical problems, such as limited access to
      telephones and the absence of a check-in desk. The therapists also reported that
      providing therapy in this setting was challenging to their professional
      identities. CONCLUSIONS: The women in the study found treatment in the
      supermarket to be an appealing alternative to the mental health clinic because of
      greater accessibility, a perceived reduction in stigma, and convenient "one-stop
      shopping" for both groceries and mental health treatment.

PMID- 12221313
TI  - A review of interventions to reduce the prevalence of parasuicide.
AB  - OBJECTIVE: The author reviewed studies of treatments for parasuicide in order to
      assist health services planners, administrators, and clinicians develop and
      improve interventions for parasuicide and decrease its prevalence. METHODS:
      Parasuicide, which is a major risk factor for completed suicide, was defined as
      any nonfatal self-injury, including suicide attempts and self-mutilation. The
      literature from 1970 to 2001 was searched using MEDLINE and PsycINFO. Only
      experimental and quasi-experimental controlled trials of treatment for
      parasuicidal individuals were selected for review. RESULTS AND CONCLUSIONS:
      Epidemiological research shows that parasuicide is a prevalent problem afflicting
      4 to 5 percent of individuals in the United States. Parasuicide is a significant
      predictor of completed suicide, which is the ninth leading cause of death in the
      United States and accounts for 50 percent more deaths than homicide. Although
      research on treatments for parasuicide is limited, several treatments have
      received empirical support. Studies of usual care indicate that empirically
      supported treatments are rarely used and that standard treatments, particularly
      hospitalization, are very expensive. The author suggests eight practical steps,
      based on the literature and established health services strategies, for improving
      services to parasuicidal individuals. These steps are establishing case
      registries, evaluating the quality of care for parasuicidal persons, evaluating
      training in empirically supported treatments for parasuicide, ensuring fidelity
      to treatment models, evaluating treatment outcomes, identifying local programs
      for evaluation, providing infrastructural supports to treating clinicians, and
      implementing quality improvement projects.

PMID- 12221314
TI  - Characteristics of new clients at self-help and community mental health agencies
      in geographic proximity.
AB  - OBJECTIVE: Self-help agencies are funded as adjuncts of, referral sources for, or
      alternatives to community mental health agencies. Little is known about how these
      two types of organization in geographic proximity interact, whom they attract as
      prospective clients, and what their clients bring to the service situation. The
      authors compared the characteristics and past service use of new enrollees of
      self-help agencies and community mental health agencies serving the same
      geographic area. METHODS: Interview assessments were conducted with 673 new users
      at ten pairs of self-help and community mental health agencies serving the same
      geographic areas. Client characteristics were evaluated with multivariate
      analysis of variance and chi square tests. RESULTS: Clients of community mental
      health agencies had more acute symptoms, lower levels of social functioning, and
      more life stressors in the previous 30 days than clients of self-help agencies.
      The self-help agency cohort evidenced greater self-esteem, locus of control, and
      hope about the future. Clients of self-help agencies had received more services
      from facilities other than self-help or community mental health agencies in the
      previous six months, and clients of self-help agencies who were not African
      American had more long-term mental health service histories. CONCLUSIONS:
      Although self-help and community mental health agencies both provide services to
      people with major mental disorders, community mental health agencies deliver
      primarily acute treatment-focused services, whereas self-help agencies provide
      services aimed at fostering socialization, mutual support, empowerment, and
      autonomy.

PMID- 12221315
TI  - Impact of modifying risk adjustment models on rankings of access to care in the
      VA mental health report card.
AB  - OBJECTIVE: Using a measure from the Veterans Administration (VA) mental health
      report card, the authors examined stability of report card rankings under
      different risk adjustment models. The study determined the impact of adding one
      variable to a standard VA risk adjustment model for access to care and examined
      whether veterans who reside in counties with VA facilities are more likely than
      veterans who reside in counties without VA facilities to use VA mental health
      services. METHODS: The authors compared the proportion of service users among
      veterans residing in counties either with or without VA facilities; the data were
      risk-adjusted by using demographic and geographic variables. A variable
      representing the presence or absence of a VA facility in each county was added to
      the risk adjustment model, and its impact on regional VA report card rankings for
      access was calculated. RESULTS: Regional rankings for access to mental health
      services by all veterans changed substantially when the additional variable was
      introduced into the risk adjustment model. Seven of 22 regions changed by five or
      more places. Access to mental health services was higher in counties with VA
      facilities, even after geographic distance to VA and non-VA hospitals was
      controlled for. CONCLUSIONS: Caution should be exercised when evaluating
      performance on the basis of report card rankings alone, even after risk
      adjustment. The results emphasize the importance of attending to observed and
      adjusted scores, along with standard deviations and standardized scores, rather
      than to rank order alone and highlight the need to educate report card users in
      their interpretation and limitations. County boundaries should be taken into
      consideration when planning VA mental health services.

PMID- 12221316
TI  - Effects of residents' depression, sleep, and demand for medication on
      benzodiazepine use in nursing homes.
AB  - OBJECTIVE: This study sought to identify risk factors associated with the
      prescription and use of benzodiazepines in nursing homes and to assess the
      prevalence and determinants of demand for benzodiazepines among nursing home
      residents. METHODS: Data were available for 2,060 residents who had participated
      in a previous study of use of medications in 18 randomly selected nursing homes
      in Wisconsin between 1986 and 1989. Data sources included nursing home and
      pharmacy records; nurses' assessments of residents' behavior, pain, sleep, and
      demand for medication; and researchers' observations of resident requests for
      medication. Measures of benzodiazepine use included benzodiazepine prescriptions,
      prevalence and extent of as-needed drug use, and chronic use as defined by Health
      Care Financing Administration guidelines. RESULTS: A quarter of the residents
      received prescriptions for benzodiazepines. Of these, 71 percent received
      prescriptions to aid sleep or to be taken at bedtime; 32 percent used
      benzodiazepines for a longer period than recommended; and 26 percent requested
      medication. Logistic regression analysis showed that residents with depression,
      pain, or sleep problems were more likely to have received benzodiazepines and to
      have requested medication. Chronic use was significantly higher among residents
      with depression, sleep problems, or multiple benzodiazepine regimens and among
      those who requested medication. Demand and sleep problems also were associated
      with higher rates of any as-needed use and with higher numbers of as-needed doses
      used. CONCLUSIONS: Efforts to improve benzodiazepine use in nursing homes must
      address the need for better assessment and management of depression, sleep, pain,
      and residents' demand for these medications.

PMID- 12221317
TI  - Smoking cessation approaches for persons with mental illness or addictive
      disorders.
AB  - OBJECTIVE: Persons with psychiatric illnesses are about twice as likely as the
      general population to smoke tobacco. They also tend to smoke more heavily than
      other smokers. This critical review of the literature identified 24 empirical
      studies of outcomes of smoking cessation approaches used with samples of persons
      with mental disorders. METHODS: The authors conducted searches of large health
      care and other databases for the years 1991 through 2001, using the key terms
      smoking, smoking cessation, nicotine, health/hospital/smoke-free policy, and
      psychiatry/ mental/substance abuse disorders. RESULTS AND CONCLUSIONS: The
      majority of interventions combined medication and psychoeducation. Although the
      studies were not uniform enough to allow a meta-analysis, the recorded quit rates
      of patients with psychiatric disorders were similar to those of the general
      population. Clinicians could usefully devote more effort to smoking cessation in
      populations with mental illness or addictions.

PMID- 12221318
TI  - Emergency involuntary psychiatric examinations in Florida.
AB  - The authors used statewide data from 2000 on 80,869 examination initiations to
      determine characteristics of emergency involuntary psychiatric examinations in
      Florida and the individuals subject to them. Information about the evidence
      indicated on the initiation forms and the types of professionals who initiated
      the examinations is presented. These data allow not only description of
      involuntary examinations and the characteristics of those subject to them for an
      entire state, but also investigation of the involvement of these individuals with
      certain services, such as mental health services, and systems, such as the
      criminal justice system.

PMID- 12221319
TI  - Factors associated with missed first appointments at a psychiatric clinic.
AB  - This study identified characteristics ofpatients who missed their intake
      appointments at a university psychiatric outpatient clinic for persons with
      serious mental illness after referral from a state agency. Of the 313 patients
      whose charts were reviewed, 113 (36 percent) missed their appointment.
      Demographic characteristics, DSM-IV diagnoses, clinician rating scales, and
      psychopharmacological therapy were compared between attenders and nonattenders.
      Five predictors of nonattendance were significant: being younger, being Hispanic,
      having a poor family support system, not taking psychotropic medications, and
      having health insurance. Persons at greater risk of missing their intake
      appointment may be prospectively identified and targeted for measures to improve
      compliance.

PMID- 12221320
TI  - Factors associated with rehospitalization among veterans in a substance abuse
      treatment program.
AB  - This study sought to determine predictors of rehospitalization among veterans in
      an inpatient substance abuse treatment program, many of whom had psychiatric
      disorders. A random sample of 600 veterans was interviewed at program entry about
      some factors not generally assessed as predictors. Information on
      rehospitalization in the two years after discharge was obtained from the
      databases of Veterans Affairs hospitals. Cox's proportional hazards model was
      used. Variables that were the strongest predictors were self-efficacy, childhood
      sexual and physical abuse, and religiosity. The results indicate that factors not
      usually investigated, such as attachment to family of origin, early physical and
      sexual abuse, and self-efficacy, are related to rehospitalization and should be
      further investigated.

PMID- 12221322
TI  - Closing a state hospital.

PMID- 12221323
TI  - Stigma and violence.

PMID- 12221324
TI  - Patients' attitudes toward antidepressants.

PMID- 12221326
TI  - Early prediction of severity in acute pancreatitis. Is this possible?
AB  - One out of ten cases of acute pancreatitis develops into severe acute
      pancreatitis which is a life threatening disorder with a high mortality rate. The
      other nine cases are self limiting and need very little therapy. The specificity
      of good clinical judgement on admission, concerning the prognosis of the attack,
      is high (high specificity) but misses a lot of severe cases (low sensitivity).
      The prediction of severity in acute pancreatitis was first suggested by John HC
      Ranson in 1974. Much effort has been put into finding a simple scoring system or
      a good biochemical marker for selecting the severe cases of acute pancreatitis
      immediately on admission. Today C-reactive protein is the method of choice
      although this marker is not valid until 48-72 hours after the onset of pain.
      Inflammatory mediators upstream from CRP like interleukin-6 and other cytokines
      are likely to react faster and preliminary results for some of these mediators
      look promising. Another successful approach has been to study markers for the
      activation of trypsinogen such as TAP and CAPAP. This is based on studies showing
      that active trypsin is the initial motor of the inflammatory process in acute
      pancreatitis. In the near future a combined clinical and laboratory approach for
      early severity prediction will be the most reliable. Clinical judgement predicts
      1/3 of the severe cases on admission and early markers for either inflammation or
      trypsinogen activation should accurately identify 50-60% of the mild cases among
      the rest, thus missing only 2-4% of the remaining severe cases. One problem is
      that there is no simple and fast method to analyze any of these parameters.

PMID- 12221327
TI  - Islet amyloid, metabolic syndrome, and the natural progressive history of type 2
      diabetes mellitus.
AB  - The presence of amyloid within the islet of the pancreas may be one of the best
      kept secrets in clinical medicine and translation of this century old finding may
      help to better understand the progressive nature of type 2 diabetes mellitus.
      Insulin resistance, metabolic syndrome, and type 2 diabetes mellitus are
      associated with multiple metabolic toxicities which result in an elevated tension
      of redox stress within the islet. Redox stress is associated with damage to
      proteins, lipids, and nucleic acids which may have a profound affect upon the
      structure and function of the islet. Earlier diagnosis at the stage of impaired
      glucose tolerance (prediabetes) and intervention may have a positive outcome on
      stabilization of the vulnerable islet and beta cell as well as the multiple
      diabetic complications. The natural history and a shift in the treatment paradigm
      of type 2 diabetes mellitus is explored as a result of these century old
      findings.

PMID- 12221328
TI  - Pancreatic involvement during the early phase of shock.
AB  - BACKGROUND: There is a lack of data concerning pancreatic involvement during
      shock. AIM: To evaluate possible pancreatic alterations in the early phase of
      shock. SETTING: Twelve consecutive patients with shock were studied within 2
      hours from the onset of illness. Seven patients died during the hospital stay: 3
      within 4 hours from admission, 3 within 4-8 hours and 1 within 12 hours. MAIN
      OUTCOME MEASURES: Amylase, lipase, C-reactive protein, amyloid A, interleukin 6,
      procalcitonin and vascular cell adhesion molecule-1 serum concentrations were
      determined on admission and 4, 8, and 12 hours afterward. All patients underwent
      imaging studies of the pancreas. RESULTS: None of the patients developed clinical
      signs or morphological alterations compatible with acute pancreatitis. Serum
      amylase levels were above the upper reference limit in 7 patients (58.3%) and
      serum lipase levels in 2 patients (16.7%; P=0.062). There were no significant
      differences found between survivors and non-survivors in the serum concentrations
      of all the proteins studied. CONCLUSIONS: In patients with shock, amylase seems
      to be more frequently elevated than lipase. None of the patients showed
      pancreatic alterations at imaging techniques.

PMID- 12221329
TI  - Detection of K-ras point mutation at codon 12 in pancreatic diseases: a study in
      a Brazilian casuistic.
AB  - OBJECTIVE: To clarify the sensitivity and the validity of K-ras point mutational
      analysis at codon 12 in Brazilian patients with pancreatic diseases, and the
      possible correlation between the presence of the mutation and the
      histopathological findings. PATIENTS: Ninety-seven Brazilian patients with
      pancreatic ductal adenocarcinoma, pancreatic neuroendocrine tumors and chronic
      pancreatitis were enrolled in this study. Forty-five patients (46%) were female
      and 52 patients (54%) were male, having an average age of 60.2+/-9.2 years for
      adenocarcinoma (n=52), 45.1+/-19.4 years for pancreatic neuroendocrine tumors
      (n=20), and 46.4+/-11.2 years for chronic pancreatitis (n=25). DNA extracted from
      11 normal human peripheric lymphocytes was utilized as a control. RESULTS: The
      sensitivity of K-ras mutational analysis was 83.3% (25/30) in paraffin-embedded
      samples and 72.7% (16/22) in surgically resected specimens of the malignancy. On
      the other hand, no mutations were found in pancreatic neuroendocrine tumors or in
      chronic pancreatitis. Regarding the histopathological grading, the higher
      positivity rate was found in poorly-differentiated adenocarcinoma (100%), and
      progressively decreased in moderately-differentiated adenocarcinoma (72.2%), and
      well-differentiated adenocarcinoma (66.6%). The positivity rate in non-classified
      adenocarcinoma was 81.8%. CONCLUSION: K-ras point mutation, in our study, is
      notably prevalent in malignancies and is absent in chronic pancreatitis and
      pancreatic neuroendocrine tumors. These results encourage us to consider the
      possibility of treatment strategies for this oncogene in the future.

PMID- 12221330
TI  - Neuropharmacological factors, biliary motility and pancreatitis.

PMID- 12221342
TI  - The back home trial: general practitioner-supported leaflets may change back pain
      behavior.
AB  - STUDY DESIGN: A single-blind randomized controlled trial of a leaflet developed
      for people with acute low back pain was compared with the usual general
      practitioner management of back pain. OBJECTIVE: To test the effectiveness of a
      patient information leaflet on knowledge, attitude, behavior, and function.
      SUMMARY OF BACKGROUND DATA: Despite the commonality of back pain in general
      practice, little evidence on the effectiveness of simple interventions such as
      leaflets and advice on self-management has been reported. On the basis of a five
      stage needs analysis, a simple leaflet was developed that considered the views of
      patients and health professionals. METHODS: For this study, 64 patients with
      acute back pain were assigned to the leaflet or control group. The participants
      were visited at home after 2 days, 2 weeks, then 3, 6, and 12 months, where they
      completed a range of self-report measures. Behavioral aspects were discretely
      recorded by a "blinded" researcher. Primary outcomes were knowledge, attitude,
      behavior, and function. RESULTS: In all, 272 home visits were undertaken. The
      findings show that at 2 weeks, knowledge about sitting posture was greater in the
      leaflet group (P = 0.006), which transferred to a behavioral difference (sitting
      with lumbar lordosis support) when participants were unaware that they were being
      observed (P = 0.009). This difference remained significant at 3 months. Patients
      in the leaflet group also were better at maintaining a wide base of support when
      lifting a light object than the control subjects throughout all five assessments.
      There were no significant differences in the functional outcomes tested.
      CONCLUSIONS: This trial demonstrates that written advice for patients can be a
      contributory factor in the initial general practitioner consultation because it
      may change aspects of knowledge and behavior. This has implications for the
      management of acute back pain, with potential health gain.

PMID- 12221343
TI  - Treatment of chronic lower back pain with lumbar extension and whole-body
      vibration exercise: a randomized controlled trial.
AB  - STUDY DESIGN: A randomized controlled trial with a 6-month follow-up period was
      conducted. OBJECTIVE: To compare lumbar extension exercise and whole-body
      vibration exercise for chronic lower back pain. SUMMARY OF BACKGROUND DATA:
      Chronic lower back pain involves muscular as well as connective and neural
      systems. Different types of physiotherapy are applied for its treatment.
      Industrial vibration is regarded as a risk factor. Recently, vibration exercise
      has been developed as a new type of physiotherapy. It is thought to activate
      muscles via reflexes. METHODS: In this study, 60 patients with chronic lower back
      pain devoid of "specific" spine diseases, who had a mean age of 51.7 years and a
      pain history of 13.1 years, practiced either isodynamic lumbar extension or
      vibration exercise for 3 months. Outcome measures were lumbar extension torque,
      pain sensation (visual analog scale), and pain-related disability (pain
      disability index). RESULTS: A significant and comparable reduction in pain
      sensation and pain-related disability was observed in both groups. Lumbar
      extension torque increased significantly in the vibration exercise group (30.1
      Nm/kg), but significantly more in the lumbar extension group (+59.2 Nm/kg; SEM
      10.2; P < 0.05). No correlation was found between gain in lumbar torque and pain
      relief or pain-related disability (P > 0.2). CONCLUSIONS: The current data
      indicate that poor lumbar muscle force probably is not the exclusive cause of
      chronic lower back pain. Different types of exercise therapy tend to yield
      comparable results. Interestingly, well-controlled vibration may be the cure
      rather than the cause of lower back pain.

PMID- 12221344
TI  - A randomized controlled trial of exercise and manipulative therapy for
      cervicogenic headache.
AB  - STUDY DESIGN: A multicenter, randomized controlled trial with unblinded treatment
      and blinded outcome assessment was conducted. The treatment period was 6 weeks
      with follow-up assessment after treatment, then at 3, 6, and 12 months.
      OBJECTIVES: To determine the effectiveness of manipulative therapy and a low-load
      exercise program for cervicogenic headache when used alone and in combination, as
      compared with a control group. SUMMARY OF BACKGROUND DATA: Headaches arising from
      cervical musculoskeletal disorders are common. Conservative therapies are
      recommended as the first treatment of choice. Evidence for the effectiveness of
      manipulative therapy is inconclusive and available only for the short term. There
      is no evidence for exercise, and no study has investigated the effect of combined
      therapies for cervicogenic headache. METHODS: In this study, 200 participants who
      met the diagnostic criteria for cervicogenic headache were randomized into four
      groups: manipulative therapy group, exercise therapy group, combined therapy
      group, and a control group. The primary outcome was a change in headache
      frequency. Other outcomes included changes in headache intensity and duration,
      the Northwick Park Neck Pain Index, medication intake, and patient satisfaction.
      Physical outcomes included pain on neck movement, upper cervical joint
      tenderness, a craniocervical flexion muscle test, and a photographic measure of
      posture. RESULTS: There were no differences in headache-related and demographic
      characteristics between the groups at baseline. The loss to follow-up evaluation
      was 3.5%. At the 12-month follow-up assessment, both manipulative therapy and
      specific exercise had significantly reduced headache frequency and intensity, and
      the neck pain and effects were maintained (P < 0.05 for all). The combined
      therapies was not significantly superior to either therapy alone, but 10% more
      patients gained relief with the combination. Effect sizes were at least moderate
      and clinically relevant. CONCLUSION: Manipulative therapy and exercise can reduce
      the symptoms of cervicogenic headache, and the effects are maintained.

PMID- 12221346
TI  - Early occupational health management of patients with back pain: a randomized
      controlled trial.
AB  - STUDY DESIGN: A randomized controlled trial in occupational health practice was
      conducted. OBJECTIVE: To study the efficacy of early management of workers with
      low back pain by occupational physicians, as compared with management by the
      supervisor only. SUMMARY OF BACKGROUND DATA: Health care and university workers
      with back pain and on sick leave for less than 1 month were included in the
      study. METHODS: Patients with low back pain for at least 10 days on sick leave
      were randomly assigned to early management by the occupational physician (n = 61)
      or to a reference group with management by the worker's supervisor during the
      first 3 months of sick leave (n = 59). The patients were observed for 1 year and
      compared in terms of time until return to work, pain intensity, functional
      disability, and general health perception. The occupational physicians were
      provided with management guidelines. RESULTS: No significant differences were
      found after 3 and 12 months of follow-up evaluation in terms of time until return
      to work (hazard ratio, 1.3; 95% CI, 0.90-1.90) or in terms of other health
      outcomes. Recurrences, however, occurred more frequently in the intervention
      group, but the total duration of sick leave in 1 year did not differ between the
      groups. CONCLUSIONS: The findings do not show a significant positive effect of an
      early intervention by occupational physicians on workers with low back pain. This
      might reflect the early phase of disability or the low intensity of the
      intervention resulting from overestimation of the physicians' compliance with the
      guidelines.

PMID- 12221348
TI  - Possible roles of CTGF/Hcs24 in the initiation and development of ossification of
      the posterior longitudinal ligament.
AB  - STUDY DESIGN: A biochemical and histochemical study investigating the role of
      CTGF/Hcs24 in the ossification of the posterior longitudinal ligament (OPLL) was
      conducted. OBJECTIVE: To clarify the involvement of CTGF/Hcs24 in ectopic bone
      formation in OPLL through endochondral ossification using human tissue. SUMMARY
      OF BACKGROUND DATA: Previous studies have shown that various cytokines are
      involved in the occurrence or development of ectopic bone formation in OPLL.
      Recently, the authors cloned an mRNA predominantly expressed in chondrocytes by
      differential display PCR and found that its gene, hcs24, is identical to that of
      connective tissue growth factor. It has been shown that CTGF/Hcs24 plays a major
      role in endochondral ossification. METHODS: Ossified ligament tissues were taken
      from seven male OPLL patients during surgery. Immunohistochemical staining was
      performed using an antibody specific for CTGF/Hcs24. Spinal ligament cells were
      isolated from five OPLL patients as well as five non-OPLL patients. The cells
      were incubated with recombinant human CTGF/Hcs24 or TGFbeta. The expression of
      ALP was analyzed by RT-PCR. For the effects of TGFbeta, the expression of
      CTGF/Hcs24 mRNA was analyzed. RESULTS: Immunohistochemical staining showed that
      chondrocytes in the transitional region from nonossified to ossified ligament
      were stained with an antibody against CTGF/Hcs24. It was found that CTGF/Hcs24
      enhanced the expression ALP mRNA in OPLL cells, whereas the expression remained
      unchanged in non-OPLL cells. The expression of CTGF/Hcs24 mRNA in OPLL and non
      OPLL cell lines was increased by TGFbeta, and there was no significant difference
      between the two groups. However, TGFbeta and CTGF/Hcs24 enhanced the expression
      of ALP mRNA only in OPLL cells. CONCLUSIONS: According to the study results,
      CTGF/Hcs24 may not only be an important factor in the development of endochondral
      ossification in OPLL, but may also be responsible for initiating osteogenesis in
      spinal ligament cells.

PMID- 12221349
TI  - Unilateral cervical facet dislocation: injury mechanism and biomechanical
      consequences.
AB  - STUDY DESIGN: Human cadaveric cervical spines were subjected to nondestructive
      repeated-measures flexibility tests before, during, and after unilateral facet
      dislocation. OBJECTIVES: To assess the relative stability and kinematics of the
      spine in the normal condition, after unilateral facet lock without bony injury
      and after reducing (unlocking) the facet dislocation. SUMMARY OF BACKGROUND DATA:
      Experimental unilateral facet dislocation has been studied only when associated
      with extensive damage to disc, bone, or both. The relative stability of the
      normal, locked, and unlocked cervical spine has not been studied. METHODS:
      Unilateral facet dislocation with minimal associated injury was created by slowly
      applying axial torque while specimens were bent laterally and flexed. Before and
      after injury, nondestructive torques were applied about each anatomic axis, while
      three-dimensional specimen motion was recorded stereophotogrammetrically.
      RESULTS: Unilateral facet dislocation was created with a mean axial torque of
      10.2 +/- 2.7 Nm. After locking, range of motion, lax zone, and stiff zone were
      significantly reduced relative to normal (P < 0.05). After unlocking, the same
      parameters were significantly increased relative to normal. The position of the
      axis of rotation shifted when the facet was locked and the centrode elongated
      after the facet was unlocked. CONCLUSIONS: Unilateral facet dislocation without
      fracture can be created with moderate loads when axial torque is applied while
      the facet is distracted. The spine is stable while the articular masses are
      locked unilaterally; however, the motion segment becomes overtly unstable after
      the facet dislocation is reduced.

PMID- 12221351
TI  - Three-dimensional motion patterns during active bending in patients with chronic
      low back pain.
AB  - STUDY DESIGN: The three-dimensional motion patterns of chronic low back pain
      (LBP) patients were studied during active motions. OBJECTIVE: To evaluate whether
      the motion patterns of coupling and asymmetry in chronic LBP patients differ from
      those in the normal population according to previous literature. SUMMARY OF
      BACKGROUND DATA: There exists little data that correlates vertebral motion with
      LBP symptoms despite extensive research. Several studies have suggested that
      patterns of motion are sensitive indicators of spinal pathology, including
      coupled motion patterns and asymmetry of motion. METHODS: In this study, 34
      chronic LBP patients enrolled for an external fixation test performed active
      bending maneuvers, during which the three-dimensional intervertebral motions were
      measured continuously with an optoelectronic camera via markers attached to the
      percutaneous transpedicular screws. If a solid connection between each marker
      carrier and vertebrae was verified, the three-dimensional rotations of the
      vertebrae were analyzed with special reference to motion asymmetries and patterns
      of coupled motion. All data were compared to the normal values in the literature
      since the methodology is not possible in asymptomatic control subjects. RESULTS:
      Seven patients were removed from the analysis because of a loose screw-bone
      interface. In the remaining patients, three distinct patterns of motion were
      observed in each direction of movement. Significant differences in the extension
      flexion ratio, the lateral bending asymmetry, and the coupled axial rotation
      lateral bending ratio were found between the chronic LBP group and the normal
      literature values. CONCLUSIONS: Chronic LBP patients exhibited motion patterns
      altered from those of the normal population. Specific differences were observed
      in coupled axial rotation during lateral bending movement, in the symmetry
      between flexion and extension, and in the symmetry be tween right and left
      lateral bending.

PMID- 12221352
TI  - Biomechanical evaluation of a bipedicular spinal fixation system: a comparative
      stiffness test.
AB  - STUDY DESIGN: This biomechanical study using cadaver thoracic spines evaluated
      the initial stiffness of two different fixation constructs using a new spinal
      implant: the bipedicular spinal fixation device (BSF). OBJECTIVE: To compare the
      biomechanical stiffness of a new construct using BSF with a regular construct
      using pedicular and laminar hooks. SUMMARY OF BACKGROUND DATA: Disadvantages of
      thoracic posterior implants and developments in in situ rod contouring led to the
      creation of a new implant for spine deformity surgery that would provide
      immediate stiffness to preserve spine correction, allow efficient postoperative
      rehabilitation, and obtain a good fusion rate. METHODS: Two age-paired groups of
      six human thoracic spines each (T3-T12) were compared: a regular group whose
      construct was in accordance with the Cotrel-Dubousset technique and the BSF
      group. In both groups, the spines were tested intact and then after injury. An
      injury was induced by transections of interspinous and anterior longitudinal
      ligaments and anterior discectomies. A three-dimensional ultrasonic measurement
      device, the Zebris 3D Motion Analyzer, was used to record the motion of the T6
      relative to the T8 vertebra under loads, and to determine the ranges of motion
      (ROMs) between intact spines and the spine construct. RESULTS: In flexion
      extension, the regular construct showed a significantly greater mean of relative
      ROMs than the BSF construct for principal rotation (88% and 69% respectively, P =
      0.015). However, no significant differences were demonstrated in any of the other
      motions. CONCLUSION: The BSF construct showed stiffness similar to that of the
      regular construct, encouraging clinical investigation.

PMID- 12221353
TI  - Human muscular and postural responses in unstable load lifting.
AB  - STUDY DESIGN: Most studies of manual material handling have focused on stable
      (fixed) loads. The muscular response during unstable load handling deserves more
      investigative attention. OBJECTIVES: To investigate muscular and postural
      responses during unstable load lifting, and to quantify the threat posed by such
      loads in the workplace. SUMMARY OF BACKGROUND DATA: Accurate assessment of load
      weight is important for lifters. Unfortunately, this information is not always
      available to individuals handling containers of liquids or shifting loads, or
      those encountering impact loading or a sudden unexpected load. METHODS: In this
      study, 12 subjects were subjected to time-variant loads, in which a box weighing
      18 kg was used to generate a sudden 12 (kg. m)/second load impact internally
      during the lifting process. Responses were investigated as a function of
      different load-shift conditions (anterior-to-posterior and posterior-to-anterior
      rolling loads and stable load), two foot placements (wide and narrow stance), and
      two lifting techniques (stoop and squat). Normalized electromyography signals,
      joint angles, and total linear length for center of pressure (COP-length) were
      investigated. RESULTS: Lifting an unstable load significantly increases total
      lifting time, COP-length, and muscular contraction levels. When responding to
      impact momentum, subjects attempted to lift with greater elbow extension and
      shoulder and trunk flexion. A more flexed knee joint (approximately an additional
      5 degrees ) was observed during preparation for load impact in the anterior-to
      posterior rolling task, allowing the formation of a more stable platform to
      compensate for the load variation. The largest erector spinae contraction for
      unstable lifting was approximately 12% to 25% greater maximal voluntary
      contraction than for the stable analog. CONCLUSIONS: The normalized
      electromyography data demonstrate that the central nervous system detects and
      responds to the need to stabilize the joints closest to the location of load
      shift perturbation.

PMID- 12221354
TI  - Outcome of anterior cervical discectomy and fusion as perceived by patients
      treated for dominant axial-mechanical cervical spine pain.
AB  - STUDY DESIGN: An extensive outcome questionnaire using a visual analog scale, the
      North American Spine Society Satisfaction Questionnaire, a Modified Roland and
      Morris disability index, and a modified Oswestry Disability Index was used to
      assess the outcome of anterior cervical discectomy and fusion for those with neck
      pain. OBJECTIVE: To document the clinical outcome for 87 patients who underwent
      anterior cervical discectomy and fusion for the primary indication of neck pain,
      as assessed after an average follow-up period of 4.4 years. SUMMARY OF BACKGROUND
      DATA: Clinical outcome studies of anterior cervical discectomy and fusion with
      validated patient-perceived outcome measurements are few. METHODS: From the
      authors' database, 87 patients were identified who had undergone an anterior
      cervical discectomy and fusion for primary indication of dominant neck pain, and
      who had completed an extensive outcome questionnaire regarding pain and self
      function at a mean 4.4-year follow-up assessment. RESULTS: This study documents a
      self-perceived satisfactory outcome rate of 82%. Patients reported on improvement
      of pain using visual analog scales, on function using modified Oswestry and
      modified Roland-Morris disability indexes, and on satisfaction using the North
      American Spine Society outcome tool. On an assessment 4.4 years on the average
      after the surgery, 82% of the patients (71/87) self-perceived their outcome to be
      good, very good, or excellent. Pain improvement was reported by 93% of the
      patients (81/87), whose average visual analog rating changed from 8.4 before
      surgery to 3.8 after surgery. The self-rated functional status improved
      approximately 50% on both the Oswestry and the modified Roland-Morris disability
      indexes. CONCLUSIONS: Properly selected patients who present with a primary
      indication of chronic neck pain report a high percentage of change in their self
      perceived level of pain and function when treated with anterior cervical
      discectomy and fusion. Patients' self-expressed improvement with surgical
      management, as compared with their preoperative dissatisfaction because of their
      neck condition, documents that this surgical treatment is a reasonable option.

PMID- 12221356
TI  - Massage for low-back pain: a systematic review within the framework of the
      Cochrane Collaboration Back Review Group.
AB  - BACKGROUND: Low back pain (LBP) is one of the most common and costly
      musculoskeletal problems in modern society. Proponents of massage therapy claim
      it can minimize pain and disability and speed return-to-normal function.
      OBJECTIVES: To assess the effects of massage therapy for nonspecific LBP. SEARCH
      STRATEGY: We searched MEDLINE, Embase, Cochrane Controlled Trials Register,
      HealthSTAR, CINAHL, and dissertation abstracts through May 2001 with no language
      restrictions. References in the included studies and in reviews of the literature
      were screened. Contact with content experts and massage associations was also
      made. SELECTION CRITERIA: The studies had to be randomized or quasirandomized
      trials investigating the use of any type of massage (using the hands or a
      mechanical device) as a treatment for nonspecific LBP. DATA COLLECTION AND
      ANALYSIS: Two reviewers blinded to authors, journals, and institutions selected
      the studies, assessed the methodologic quality using the criteria recommended by
      the Cochrane Collaboration Back Review Group, and extracted the data using
      standardized forms. The studies were analyzed in a qualitative way because of
      heterogeneity of population, massage technique, comparison groups, timing, and
      type of outcome measured. RESULTS: Nine publications reporting on eight
      randomized trials were included. Three had low and five had high methodologic
      quality scores. One study was published in German, and the rest, in English.
      Massage was compared with an inert treatment (sham laser) in one study that
      showed that massage was superior, especially if given in combination with
      exercises and education. In the other seven studies, massage was compared with
      different active treatments. They showed that massage was inferior to
      manipulation and transcutaneous electrical nerve stimulation; massage was equal
      to corsets and exercises; and massage was superior to relaxation therapy,
      acupuncture, and self-care education. The beneficial effects of massage in
      patients with chronic LBP lasted at least 1 year after the end of the treatment.
      One study comparing two different techniques of massage concluded in favor of
      acupuncture massage over classic (Swedish) massage. CONCLUSIONS: Massage might be
      beneficial for patients with subacute and chronic nonspecific LBP, especially
      when combined with exercises and education. The evidence suggests that
      acupuncture massage is more effective than classic massage, but this needs
      confirmation. More studies are needed to confirm these conclusions, to assess the
      effect of massage on return-to-work, and to measure longer term effects to
      determine cost-effectiveness of massage as an intervention for LBP.

PMID- 12221357
TI  - Relations between standing stability and body posture parameters in adolescent
      idiopathic scoliosis.
AB  - STUDY DESIGN: A retrospective study of standing imbalance and body posture in 71
      able-bodied girls and subjects with adolescent idiopathic scoliosis was
      conducted. OBJECTIVE: To test the hypothesis that postural parameters are related
      to standing stability parameters. SUMMARY OF BACKGROUND DATA: Spinal deformity
      not only modifies the shape of the trunk, but also changes the relations between
      body segments affecting posture in scoliotic children. These postural adaptations
      to the scoliotic curve progression could be linked in part to increased body sway
      in upright standing. This has not yet been related to specific postural
      parameters involving the head, trunk, and pelvis in nontreated idiopathic
      scoliosis. METHODS: The head, trunk, and pelvis orientations of each subject were
      measured by a Flock of Bird system. An AMTI force platform was used to assess
      quiet standing stability and to monitor the position and displacement of the
      center of pressure (COP). The center of mass (COM) excursion was estimated from a
      biomechanical model using force plate information only. Analyses of variance
      (ANOVAS) were performed to determine the statistical differences between the
      scoliotic and nonscoliotic subjects, and backward stepwise multiple regression
      analyses were performed to identify any correlation between measures of quiet
      standing stability and body postural parameters RESULTS: The scoliotic group was
      characterized by a decrease in standing stability. There was an increase in the
      sway areas measured by the variations of the COP and COM. From the backward
      stepwise multiple regression analysis, it appears that for the able-bodied girls,
      the body posture parameters were correlated only with the mean anteroposterior
      center of pressure (COP(AP)) position. For the scoliotic group, the sway areas
      and the mean position of the centers of pressure and the COP(AP)-COM(AP) were
      correlated significantly with body posture parameters. The higher COP-COM
      differences for the scoliotic group were attributed to a greater neuromuscular
      demand to maintain standing balance. The coefficients of correlation of the
      multiple regression analyses ranged from 0.64 to 0.85 for the nonscoliotic group
      and from 0.55 to 0.72 for the scoliotic group. CONCLUSIONS: The use of backward
      stepwise multiple correlations highlighted the interaction between several body
      parameters and their relation to standing stability in both able-bodied girls and
      scoliotic subjects. The scoliotic group displayed a much larger number of
      correlations between standing stability and body posture parameters than the
      nonscoliotic group. Standing imbalance was related to altered body posture
      parameters measured in the frontal and horizontal planes only. Although the
      correlation coefficients were relatively high, factors other than body posture
      parameters appeared related to standing imbalance in adolescent idiopathic
      scoliosis. These findings support the concept of either a primary or a secondary
      dysfunction in the postural regulation system of scoliotic subjects.

PMID- 12221358
TI  - The relation among spinal geometry on MRI, paraspinal electromyographic
      abnormalities, and age in persons referred for electrodiagnostic testing of low
      back symptoms.
AB  - STUDY DESIGN: A retrospective EMG study with blinded radiologic measurement was
      conducted. OBJECTIVE: To determine the relation among spinal measurements on MRI,
      paraspinal denervation, and age in patients referred for electrodiagnostic and
      radiologic evaluation of low back pain. SUMMARY OF BACKGROUND DATA: Spinal
      pathology, including disc herniation and spinal stenosis, can cause denervation
      of the paraspinal muscles. Various mechanisms including direct compression,
      inflammation, vascular compromise, and mechanical stretch of the posterior
      primary ramus may play a role in denervation. The relation between the amount of
      denervation and the size of the spinal canal can assist in understanding the
      pathophysiology of back pain. Since paraspinal denervation may increase with age
      in asymptomatic persons, age is an important covariable. METHODS: At a university
      hospital, 44 patients referred to undergo both electrodiagnostic evaluation and
      MRI for low back pain were studied. The study investigated the relation among the
      following: 1) axial MRI spinal measurements (canal transverse diameter,
      anteroposterior diameter, and area; thecal sac anteroposterior diameter and area;
      and the radiologist's overall impression at each level) and denervation
      measurements in terms of scores on the MiniPM, a quantified needle
      electromyographic measure of paraspinal denervation; 2) various models of
      multilevel spinal compression (smallest, smallest two, and average spinal levels
      for each measurement) and MiniPM scores; and 3) MRI spinal canal measurements and
      age. RESULTS: Although individual MRI measurements and combinations of
      measurements did not relate to MiniPM scores, the radiologist's impression was
      significantly related. The "smallest two" levels measurement had the strongest
      relation (r = 0.400; P < 0.007). Age related to the MiniPM scores (P = 0.004) and
      radiologic impression (P = 0.031). A regression suggested that MiniPM was an
      independent predictor of age. CONCLUSIONS: The radiologist's overall impression
      is more accurate than axial image measurements in predicting paraspinal
      denervation. A combination score of the smallest two levels is the most accurate,
      perhaps relating to the vascular pathophysiology of stenosis. There is more
      denervation with increasing age in this symptomatic population.

PMID- 12221360
TI  - Reliability and validity of lumbosacral spine radiograph reading by
      chiropractors, chiropractic radiologists, and medical radiologists.
AB  - STUDY DESIGN: A cross-sectional diagnostic study was conducted in two sessions.
      OBJECTIVE: To determine and compare the reliability and validity of
      contraindications to chiropractic treatment (infections, malignancies,
      inflammatory spondylitis, and spondylolysis-listhesis) detected by chiropractors,
      chiropractic radiologists, and medical radiologists on plain lumbosacral
      radiographs. SUMMARY OF BACKGROUND DATA: Plain radiography of the spine is an
      established part of chiropractic practice. Few studies have assessed the ability
      of chiropractors to read plain radiographs. METHODS: Five chiropractors, three
      chiropractic radiologists and five medical radiologists read a set of 300 blinded
      lumbosacral radiographs, 50 of which showed an abnormality (prevalence, 16.7%),
      in two sessions. The results were expressed in terms of reliability (percentage
      and kappa) and validity (sensitivity and specificity). RESULTS: The interobserver
      agreement in the first session showed generalized kappas of 0.44 for the
      chiropractors, 0.55 for the chiropractic radiologists, and 0.60 for the medical
      radiologists. The intraobserver agreement showed mean kappas of 0.58, 0.68, and
      0.72, respectively. The difference between the chiropractic radiologists and
      medical radiologists was not significant. However, there was a difference between
      the chiropractors and the other professional groups. The mean sensitivity and
      specificity of the first round, respectively was 0.86 and 0.88 for the
      chiropractors, 0.90 and 0.84 for the chiropractic radiologists, and 0.84 and 0.92
      for the medical radiologists. No differences in the sensitivities were found
      between the professional groups. The medical radiologists were more specific than
      the others. CONCLUSIONS: Small differences with little clinical relevance were
      found. All the professional groups could adequately detect contraindications to
      chiropractic treatment on radiographs. For this indication, there is no reason to
      restrict interpretation of radiographs to medical radiologists. Good professional
      relationships between the professions are recommended to facilitate
      interprofessional consultation in case of doubt by the chiropractors.

PMID- 12221362
TI  - Cervical spine lesions after road traffic accidents: a systematic review.
AB  - STUDY DESIGN: A systematic critical literature review. OBJECTIVES: To determine
      whether occult pathoanatomical lesions in the cervical spine of road traffic
      fatalities exist and if they can be identified using optimal autopsy techniques.
      SUMMARY OF BACKGROUND DATA: Previous investigations have examined pathoanatomical
      conditions of the cervical spine of road traffic fatalities. However, different
      methods of investigation have been used, and results of studies are conflicting.
      Hence, potential pathoanatomical conditions in fatalities and survivors remain a
      controversial issue. METHODS: Articles were retrieved searching the MEDLINE,
      Mantis, and Cochrane libraries. Studies examining the cervical spine of road
      traffic fatalities at autopsy were included and evaluated according to a set of
      quality criteria. For in-depth review, only studies using surface cryoplaning
      microtomy autopsy technique and a control group were included. RESULTS: Twenty
      seven articles of which three fulfilled the quality criteria were reviewed. In
      these studies, subtle pathoanatomical lesions were found in the cervical
      intervertebral discs, cartilaginous endplates, and the articular surfaces and
      capsules of the zygapophysial joints. The lesions were found exclusively in the
      traumatized patients and in none of the patients in the control group.
      CONCLUSIONS: Occult pathoanatomical lesions in the cervical intervertebral disc
      and zygapophysial joints after fatal road traffic trauma may exist. Present
      imaging methods, especially conventional radiography, do not visualize these
      subtle lesions; hence, underreporting of pathoanatomical lesions during standard
      autopsy is probably common. These findings may have clinical relevance in the
      management of road traffic trauma survivors with potentially similar
      pathoanatomy.

PMID- 12221364
TI  - Surgical tracheostomy versus percutaneous dilational tracheostomy in patients
      with anterior cervical spine fixation: preliminary report.
AB  - STUDY DESIGN: A prospective, randomized study. OBJECTIVES: To compare the
      incidence of perioperative and early postoperative complications of surgical
      tracheostomy (ST) vs. ultrasound-guided percutaneous dilational tracheostomy
      (PDT) in patients with anterior cervical spine fixation (ACSF). SUMMARY OF
      BACKGROUND DATA: The patients with ACSF after acute spinal cord injury often
      require tracheostomy. Surgical tracheostomy is burdened with relatively high
      incidence of peristomal infections, and, recently, ultrasound-guided PDT is
      proposed in patients with ACSF. METHODS: Sixteen adult patients who underwent
      tracheostomy after acute spinal cord injury and ACSF were analyzed. The patients
      were randomly assigned to two groups: eight patients (six males; age range, 24-59
      years) who underwent ST and eight patients (seven males; age range, 19-47 years)
      who underwent ultrasound-guided PDT with dilational forceps technique. The
      incidence of peri- and early postoperative complications was followed up, as well
      as the stoma infections and the duration of the procedure. RESULTS: Not one
      patient from either group had any major perioperative complication of
      tracheostomy. In each group, there was one case of prolonged bleeding, which
      stopped spontaneously inside 24 hours. In two patients (25%) from the ST group,
      purulent infection of the stoma was verified during subsequent treatment at an
      intensive care unit. The average time of ST was 21 +/- 7 minutes; the average
      time of ultrasound-guided PDT was 8 +/- 6 minutes (P < 0.05). CONCLUSIONS: Our
      preliminary data demonstrate that ultrasound-guided PDT as regards to
      complications is at least equally safe as ST; at the same time, it is much
      quicker method, probably with less late infections of the stoma, which could be
      an important advantage in patients with ACSF.

PMID- 12221366
TI  - A new millenium for spinal cord regeneration: growth-associated genes.
AB  - INTRODUCTION: Neurons surviving spinal cord injury undergo extensive
      reorganization that may result in the formation of functional synaptic contacts.
      Many neurons, however, fail to activate the necessary mechanisms for successful
      regeneration. In this review, we discuss the implications of growth cone genes
      that we have correlated with successful spinal cord axonal regeneration. METHOD:
      Factors that inhibit regeneration, and activation of genes that promote it are
      discussed. RESULTS/DISCUSSION: The early progress n understanding mechanisms that
      seem to promote or inhibit regeneration in the central nervous system may have
      significant clinical utility in the future.

PMID- 12221367
TI  - Re: Jackson PR, et al. Congruent spinopelvic alignment on standing lateral
      radiographs of adult volunteers. Spine 2000;25:2808-285.

PMID- 12221368
TI  - Re: Haldeman, et al. Unpredictability of cerebrovascular ischemia associated with
      cervical spine manipulation therapy. Spine 2002;1:27.

PMID- 12221369
TI  - Re: Blanck P, Schmeling JL. Americans with Disabilities Act: recent and pending
      U.S. Supreme Court decisions and implications for spine professionals. Spine
      2002;27:439-43.

PMID- 12221370
TI  - Re: Shimamoto, et al. Biomechanical evaluation of anterior spinal instrumentation
      systems for scoliosis. Spine 2001;26:2701-8.

PMID- 12221371
TI  - Re: Parisini P, Di Silvestre M, Greggi T, et al. Lumbar disc excision in children
      and adolescents. Spine 2001;26:1997-2000.

PMID- 12221372
TI  - The lateral buttress: an anatomic feature of the lumbar pars interarticularis.
AB  - STUDY DESIGN: A morphometric study of the lateral buttress region of the lumbar
      pars interarticularis from L1-L5 on 10 dried lumbar spines was performed.
      OBJECTIVE: To qualitatively describe and quantitatively evaluate this portion of
      the pars and to discuss its clinical and surgical relevance. BACKGROUND: The
      "lateral buttress" is a bony bridge connecting the superolateral edge of the
      inferior facet to the pedicle/transverse process junction, offering structural
      support to the pars interarticularis at upper lumbar levels. To date, no anatomic
      study has evaluated this structure. METHODS: Direct measurements using vernier
      calipers were taken at each level, L1-L5, from 10 dried lumbar spines. Surface
      area of the buttress was calculated and compared statistically for differences
      between each level, as well as normalized relative to L3. RESULTS: The surface
      areas of the buttresses at L1-L3 were similar, measuring near 80 +/- 10 mm2. At
      L4, it measured 50 +/- 10 mm2. And at L5, it measured 15 +/- 5 mm2. These
      differences were statistically significant. Normalized data showed the buttress
      at L4 to be 40% smaller and at L5 to be 80% smaller than at upper levels.
      CONCLUSIONS: This study provides descriptive and anatomic data regarding the
      lateral buttress portion of lumbar pars interarticularis. The broad buttress of
      the upper lumbar levels offers support to the pars but can confuse anatomic
      guidelines for pedicle screw placement and paraspinal approaches. The narrow
      buttress of lower lumbar levels makes pedicle screw placement and the paraspinal
      approach easier, but it lessens support to the pars, making spondylolysis and
      iatrogenic instability more likely.

PMID- 12221373
TI  - A systematic review of the passive straight leg raising test as a diagnostic aid
      for low back pain (1989 to 2000).
AB  - STUDY DESIGN: A systematic review. OBJECTIVES: This systematic review sought
      papers (January 1989-January 2000) on the passive straight leg raising test
      (PSLR) as a diagnostic component for low back pain (LBP) to identify, summarize,
      and assess developments in the test procedure, the factors influencing PSLR
      outcome, and the clinical significance of that outcome. SUMMARY OF BACKGROUND
      DATA: Previous studies suggested that the PSLR tractioned the sciatic nerve and
      that diminished leg elevation with reproduced pain indicated low lumbar
      intervertebral disc pathology. METHODS: Searches on six computerized
      bibliographic databases identified publications written about the PSLR. Papers
      were excluded if they were published before January 1989, were non-English
      language papers, or employed either an active SLR or a PSLR for purposes other
      than LBP diagnosis. The references of qualifying papers (and the references of
      references) were searched. Contact with primary authors, and others known to be
      active in this field, was attempted. RESULTS: The PSLR procedure remains
      unchanged. The influence of hip rotation during the PSLR was discussed without
      consensus. Biomechanical devices improved intra- and interobserver reliability
      and so increased test reproducibility. Hamstrings were found to have a defensive
      role in protecting nerve roots by limiting PSLR range in cases of nerve root
      inflammation. A small diurnal variation in the PSLR may imply a poorer prognosis.
      A positive PSLR at 4 months after lumbar intervertebral disc surgery predicted
      poor reoperative outcome, and a negative 4-month PSLR predicted excellent
      outcome. The influence of psychosocial factors was not discussed, neither was the
      diagnostic significance of a negative PSLR outcome. CONCLUSIONS: There remains no
      standard PSLR procedure, no consensus on interpretation of results, and little
      recognition that a negative PSLR test outcome may be of greater diagnostic value
      than a positive one. The causal link between LBP pathology and hamstring action
      remains unclear. There is a need for research into the clinical use of the PSLR;
      its intra- and interobserver reliability; the influences of age, gender, diurnal
      variation, and psychosocial factors; and its predictive value in lumbar
      intervertebral disc surgery.

PMID- 12221374
TI  - Pseudogout attack of the lumbar facet joint: a case report.
AB  - STUDY DESIGN: A case of acute low back pain caused by pseudogout attack of the
      lumbar facet joint is reported. OBJECTIVE: To report a new cause of acute low
      back pain previously unreported in the literature. SUMMARY OF BACKGROUND DATA:
      There have been some reports of lumbar spinal stenosis caused by calcium
      pyrophosphate dihydrate crystal deposition. However, there are no known reports
      of pseudogout attack of the lumbar facet joint. METHODS: An axial magnetic
      resonance imaging scan demonstrated joint effusion at the level of the bilateral
      L4-L5 facet joint. Aspiration of the left L4-L5 facet joint yielded 1.5 mL of pus
      like synovial effusion. Multiple cultures of synovial fluid tested negative for
      bacteria and fungi, whereas compensated polarized light microscopy revealed
      monoclinic or triclinic crystals with a positive birefringence. RESULTS: The
      symptoms of acute low back pain lasted for 3 days. Local and systemic
      inflammatory signs, as well as symptoms, gradually improved after joint
      aspiration. A follow-up evaluation 8 months after lumbar facet joint aspiration
      showed complete resolution of pain and no neurologic deficit. CONCLUSIONS:
      Pseudogout attack of the lumbar facet joint is rare, but this clinical entity
      should be added to the differential diagnosis of acute low back pain.

PMID- 12221375
TI  - Intraoperative antepulsion of a fusion cage in posterior lumbar interbody fusion:
      a case report and review of the literature.
AB  - STUDY DESIGN: A case of intraoperative anterior migration into the abdominal
      cavity of a titanium fusion cage in the course of posterior lumbar interbody
      fusion. OBJECTIVES: To explain the importance of a proper introduction of the
      fusion cages in the vertebral space and the necessity of intraoperative
      fluoroscopy study in both planes, frontal and lateral, respectively, to confirm
      the proper position of the implants. A potential serious complication of fusion
      cage instrumentation and the limited literature on this subject are reviewed.
      SUMMARY OF BACKGROUND DATA: Early reports regarding fusion cage instrumentation
      have been encouraging. However, the potential benefits are better defined than
      the potential complications. METHODS: A patient had anterior migration of a
      fusion cage intraoperatively in the course of posterior lumbar interbody fusion.
      One day later, the patient underwent surgical laparotomy to extract the migrated
      implant and a repeat posterior procedure that included bilateral posterior fusion
      with insertion of pedicle instrumentation. RESULTS: One year after the second
      operation, the patient remains pain-free, and no abdominal lesions or neurologic
      deficits were observed. CONCLUSIONS: The various types of spinal fusion
      operations are associated with specific complications. A through knowledge of the
      procedures and possible complications, as well as meticulous surgical technique,
      can help minimize these. Once complications do occur, prompt recognition and
      treatment should minimize the long-term sequelae.

PMID- 12221376
TI  - Chronic alpha1-adrenergic blockade improves hypertension and renal injury in L
      NAME and low-renin L-NAME-DOCA hypertensive rats.
AB  - BACKGROUND: The present study investigated the contribution of alpha1-adrenergic
      blockade to hypertension induced by long-term blockade of nitric oxide and
      chronic treatment with deoxycorticosterone acetate (DOCA), which produced a low
      renin model of hypertension. We studied the effects of chronic administration of
      prazosin, an alpha1-receptor antagonist, on blood pressure (BP), renal injury,
      and other variables in N(omega)-nitro-L-arginine methyl ester (L-NAME) and L
      NAME+DOCA hypertensive rats. MATERIAL/METHODS: The rats were divided into 6
      groups: Control, DOCA, L-NAME, L-NAME+DOCA, L-NAME+ prazosin, and L
      NAME+DOCA+prazosin. Tail systolic BP was measured twice a week. After a 6-week
      evolution, mean arterial pressure (MAP) was measured, along with selected
      metabolic, morphological and renal variables. RESULTS: The final MAP values were
      105+/-1 for Control, 107+/-0.6 for DOCA, 153+/-3 for L-NAME, 175+/-2 for L
      NAME+DOCA, 126+/-2 for L-NAME+prazosin and 127+/-5 for L-NAME+DOCA+prazosin.
      Proteinuria and hyaline arteriopathy were prevented in L-NAME+prazosin rats and
      markedly attenuated in the L-NAME+DOCA+prazosin group. Plasma urea and creatinine
      were significantly increased in the L-NAME+DOCA group, but not in the L-NAME+
      DOCA+prazosin group as against controls. The DOCA and DOCA+L-NAME groups showed
      relative renal and cardiac hypertrophy, which was not observed in the DOCA+L
      NAME+prazosin group. CONCLUSIONS: Alpha1-adrenergic tone plays an important role
      in the increased BP and renal injury of L-NAME hypertension. Our results also
      indicate that when PRA is suppressed by DOCA in L-NAME hypertension, the
      increased BP and renal injury are largely dependent on the alpha1-adrenergic
      tone.

PMID- 12221377
TI  - Biomedical research, oral medicine, and the future.

PMID- 12221378
TI  - Automobile supplemental restraint system-induced injuries.

PMID- 12221379
TI  - Adenomatoid odontoma.

PMID- 12221380
TI  - Treatment of odontogenic keratocysts: a follow-up of 255 Chinese patients.
AB  - OBJECTIVE: The purpose of this study was to report our experience in the surgical
      treatment of 484 Chinese patients with follow-up in 255 cases. METHODS: A
      retrospective analysis was conducted of all odontogenic keratocysts that were
      surgically treated and histopathologically diagnosed between 1962 and 1998. The
      odontogenic keratocysts were surgically treated with enucleation,
      marsupialization followed by secondary enucleation, and resection with or without
      continuity defects. The recurrence rate was evaluated for the patients followed
      more than 3 years. RESULTS: Of a total of 489 odontogenic keratocysts, 327
      (66.87%) were found in the mandible and 162 (33.13%) in the maxilla. Follow-up
      data were obtained in 255 patients. Recurrence was found in 31 cases (15.27%) in
      203 patients treated with enucleation after an observation period of 3 to 29
      years. Twenty-nine recurrences (17.79%) were found in 163 patients treated with
      enucleation alone, two recurrences (6.70%) were seen in 29 patients who received
      Carnoy's solution fixation of the cyst wall before enucleation, and no recurrence
      was found in 11 cases treated with marsupialization in combination with secondary
      enucleation. No recurrence was seen in 52 patients treated with resection.
      CONCLUSION: Odontogenic keratocysts treated with enucleation alone have a higher
      recurrence rate. Enucleation with adjunctive treatment can decrease recurrence
      rate. Radical excision has no recurrence but does have the highest morbidity rate
      and should be reserved for multiple recurrent cysts after conservative means.

PMID- 12221381
TI  - Comparison of topical anesthesia of 20% benzocaine and 60% lidocaine gel.
AB  - OBJECTIVE: The purpose of this study was to determine the efficacies of 2 topical
      anesthetics commonly used in dentistry. STUDY DESIGN: The alveolar mucosa of the
      upper incisor apices of 20 healthy male volunteers was applied for 20 minutes
      with either 20% benzocaine gel or nothing as a control. The second part of
      experiment was done with 60% lidocaine gel and vehicle as control. Three methods
      of stimulation were given, and the pain rating score and visual analog scale were
      measured after each stimulation. RESULTS: Twenty percent benzocaine did not
      significantly alter pain perception as measured by the pain rating score and
      visual analog scale with these 3 methods of stimulation. In contrast, 60%
      lidocaine significantly reduced pain perception according to these measurements.
      We conclude that 60% lidocaine gel is effective for topical anesthesia before
      infiltration anesthesia.

PMID- 12221382
TI  - A new method of continuous maxillary nerve block with an indwelling catheter.
AB  - OBJECTIVE: We describe continuous maxillary nerve block at the pterygopalatine
      fossa and investigate the efficacy of this technique for perioperative pain
      control in oral surgery. STUDY DESIGN: Sixteen patients undergoing radical
      maxillary sinusotomy were enrolled; group I (n = 8) received general anesthesia
      without maxillary nerve block, and group II (n = 8) received maxillary nerve
      block before general anesthesia. The intraoperative concentration of sevoflurane,
      the extent of blockade, and total analgesics (diclofenac sodium) needed after
      surgery were recorded. RESULTS: The mean sevoflurane concentration was
      significantly lower in group II. Diclofenac sodium consumption was significantly
      reduced in group II. CONCLUSION: Indwelling maxillary nerve catheter methods
      decrease anesthetic consumption and provide good postoperative analgesia.

PMID- 12221383
TI  - Sex-dependent differences in the craniofacial morphology of children with a sleep
      related breathing disorder.
AB  - OBJECTIVE: The purpose of this article was to compare the craniofacial morphology
      and hyoid bone position of preschool girls and boys with sleep-related breathing
      disorder (SBD). STUDY DESIGN: The control groups consisted of girls and boys
      without ear, nose, and throat disorders. After lateral cephalometric radiographs
      were taken, the children were selected on the basis of the head position in
      relation to the true horizontal. Thirty-eight cephalometric variables were
      determined. RESULTS The findings indicate that boys with SBD had a larger
      anterior lower facial height and a more anterior hyoid bone position than girls
      with SBD. However, the distance between the third cervical vertebra and the hyoid
      bone was a constant value among girls and boys with SBD. Girls with SBD had a
      sagittally narrower pharyngeal airway space than boys with SBD. CONCLUSION: These
      findings suggest that boys with SBD have a skeletal risk factor, whereas girls
      with SBD have an airway risk factor. In conclusion, the difference in risk
      factors may have some bearing on the greater incidence of SBD in both boys and
      men.

PMID- 12221384
TI  - A simple technique for the determination of salivary gland hypofunction.
AB  - OBJECTIVE: Present volumetric or gravimetric techniques for measuring saliva
      output are often cumbersome and, therefore, not generally used. In the present
      study, a simple approach to study the weight loss of a standard hard sugar candy
      after 3 minutes of passive incubation between tongue dorsum and palate was
      tested. STUDY DESIGN: Subjects (n = 59), 27 of whom had a subjective complaint of
      dry mouth and the rest who were healthy control subjects, were tested with this
      procedure, together with gravimetric measurements of stimulated and unstimulated
      saliva output from various glands (parotid, submandibular, and sublingual).
      Correlations between a decrease in candy weight and salivary flow rate were
      determined for the 2 groups of subjects, taken separately, as well as for the
      entire subject population, by using the Pearson product moment correlation.
      RESULTS: In most cases, highly significant associations were found, particularly
      when comparing candy weight loss with stimulated parotid and submandibular and
      sublingual saliva. Data were submitted to dichotomous analysis and divided
      according to salivary flow rate by using a cutoff 0.23 g for candy loss; the
      sensitivity, specificity, and positive predictive values were 92%, 85%, and 82%,
      respectively. CONCLUSIONS: The candy weight-loss test is a simple, rapid measure
      of salivary hypofunction, which correlates with saliva output and reports of
      subjective dry mouth.

PMID- 12221385
TI  - Elevated blood pressure is not related to saliva flow in patients with Sjogren's
      syndrome.
AB  - OBJECTIVE: The purpose of this study was to determine whether systolic and
      diastolic blood pressures are associated with salivary flow, dry mouth, or dry
      eye symptoms in patients with primary Sjogren's syndrome as compared with
      xerostomic control subjects. STUDY DESIGN: One hundred forty consecutive patients
      seen at the Sjogren's Syndrome Clinic were categorized retrospectively with
      various classification schemes: (1) subjective dry mouth; (2) subjective dry eye;
      (3) European criteria; and (4) international criteria. Data collection included
      age, gender, systolic blood pressure, diastolic blood pressure, salivary flow
      rate, focus score, Schirmer's test, and laboratory findings, including
      antinuclear antibodies, anti-SSA, anti-SSB, IgG, IgA, IgM, erythrocyte
      sedimentation rate, and rheumatoid factor. RESULTS: No meaningful associations of
      salivary flow rates with systolic or diastolic blood pressures were found in
      patients with Sjogren's syndrome or in xerostomic control subjects. An inverse
      correlation was seen between salivary flow and elevated diastolic blood pressure
      in xerostomic control subjects only. CONCLUSION: Elevated blood pressure was not
      related to saliva flow in patients with Sjogren's syndrome.

PMID- 12221386
TI  - Association of salivary flow rate with oral function in a sample of community
      dwelling older adults in Japan.
AB  - OBJECTIVE: The purpose of this study was to determine the association of
      stimulated salivary flow rate with perceived salivary flow and various oral
      symptoms among a group of independently living elderly persons. STUDY DESIGN: The
      subjects were 351 persons (189 men and 162 women) with a mean age of 66.7 +/- 4.3
      years. Stimulated whole saliva was collected with the mastication method. Self
      assessed chewing ability and satisfaction with oral function also were evaluated.
      A multiple logistic regression analysis was used to determine whether an
      independent variable was statistically significant. RESULTS: Hyposalivation (<
      0.5 mL/min) was significantly associated with gender (odds ratio, 1.67; P < .05).
      Hyposalivation (odds ratio, 3.40; P <.05) and low perceived salivary flow (odds
      ratio, 5.35; P <.05) were significantly associated with dissatisfaction with
      tasting. Low perceived salivary flow was also significantly associated with self
      assessed chewing ability (odds ratio, 3.32; P <.01). CONCLUSION: This study
      suggested that hyposalivation and low perceived salivary flow were related to
      chewing ability and satisfaction with tasting foods.

PMID- 12221387
TI  - Effect of professional oral health care on the elderly living in nursing homes.
AB  - OBJECTIVE: We evaluated the effectiveness of professional oral health care (POHC)
      given by dental hygienists once a week for 24 months to 141 elderly persons
      needing daily care and living in 2 nursing homes. STUDY DESIGN: Elderly subjects
      with POHC and without POHC living in 2 nursing homes were examined for 24 months
      to detect any fevers of 37.8 degrees C or more and the prevalence of fatal
      aspiration pneumonia. The numbers of Staphylococcus species and Candida albicans
      in swab samples from oral cavities were compared between the POHC group and the
      non-POHC group. The amounts of methylmercaptan exhaled in the POHC group were
      determined and compared with those in the non-POHC group. RESULTS: The prevalence
      of fevers of 37.8 degrees C or more in the subjects receiving POHC was
      significantly lower than in the non-POHC group (P < .05). We found that the ratio
      of fatal aspiration pneumonia in the POHC group during the 24 months was
      significantly lower than in the non-POHC group (P < .05). Numbers of C albicans
      species in samples obtained from the oral cavity after 6 months of POHC were
      significantly lower than those in the non-POHC group (P < .01). POHC resulted in
      the reduction of the presence of Staphylococcus but not to a statistically
      significant extent. The amounts of methylmercaptan exhaled by the POHC group were
      significantly less than those of the non-POHC group (P <.05). CONCLUSION: This
      study showed that POHC administered by dental hygienists to a group of elderly
      patients needing daily nursing care was associated with a reduction in prevalence
      of fever and fatal pneumonia.

PMID- 12221388
TI  - Oral and clinical characteristics of a group of patients with Turner syndrome.
AB  - OBJECTIVE: The loss of the X chromosome in girls with Turner syndrome (TS)
      affects the shape and the size of craniofacial structures. Few studies have been
      reported on female patients with TS in South America. Records of odontologic
      alterations of 23 Argentinian patients with TS were compared with those of 25
      girls in a control group, and associations were made with medical indications.
      STUDY DESIGN: Oral clinical diagnoses were completed with periapical, occlusal,
      panoramic, and orthopantomograms; urine and blood determinations were performed
      by conventional methods. RESULTS: Blood phosphorus and calcium levels were
      altered, and osteoporosis was detected. In some patients, TS was associated with
      autoimmune thyroiditis. Control subjects had normal blood and urine values. The
      decayed, missing, and filled permanent surfaces index for temporary teeth was
      statistically higher for the control group. About 78% of the patients had
      hypoplasia, 65% had reduced root length and bifurcated roots, and 100% had high
      arch palate. Incisor asymmetry was also observed. CONCLUSIONS: Medical and
      laboratory indexes are essentially indicative of hormone alterations. TS patients
      have a particular oral anatomy that could be closely related to an alteration in
      calcium and phosphorus metabolism.

PMID- 12221389
TI  - Dirofilaria repens presenting as a premasseteric nodule.
AB  - Dirofilariasis is a rare zoonosis that is mainly seen with subcutaneous or
      pulmonary involvement. Natural hosts are dogs, cats, jackals, and raccoons;
      however, humans can rarely become an accidental host for the parasite. In the
      reported case, infection manifested as a subcutaneous nodule, representing a
      significant diagnostic challenge for both the surgeon and the pathologist. A case
      of a 62-year-old man with a premasseteric soft tissue mass caused by Dirofilaria
      repens is presented with histopathologic confirmation.

PMID- 12221390
TI  - Clinicopathologic characterization of oral angioleiomyomas.
AB  - OBJECTIVE: The purpose of this study was to better define the clinicopathologic
      features of oral angioleiomyomas. STUDY DESIGN: A retrospective search was
      performed for angioleiomyomas among all smooth muscle tumors accessioned from
      1963 to 2001 in an oral pathology service. Twelve lesions met histopathologic
      criteria for inclusion in the study and were combined with 97 additional cases
      identified from the English language literature, yielding 109 cases for
      evaluation. RESULTS: The mean age of the patients with oral angioleiomyomas was
      45.0 years, with a 1.43:1 male to female predilection. The most frequently
      reported site was the lip, in 48.6% of patients, followed by the palate (21.1%),
      buccal mucosa and tongue (each 9.2%), mandible (8.3%), and buccal sulcus, labial
      sulcus, floor of mouth, and gingiva (each 0.9%). Most mucosal lesions varied in
      size from a few millimeters to 2 cm, with most central lesions of the mandible
      measuring greater than 2 cm. Although angioleiomyomas are vascular lesions, only
      55.9% of cases appeared red, blue, or purple; the remainder were gray, white, or
      the color of normal mucosa. Tumors were typically described as painless and
      manifested a low growth rate. All lesions were well circumscribed and composed of
      numerous vascular spaces surrounded by thick smooth muscle walls. CONCLUSION:
      Oral angioleiomyomas are benign smooth muscle tumors with a limited degree of
      morbidity. Careful histologic inspection is necessary to distinguish these
      lesions from their malignant counterpart, the leiomyosarcoma. Surgical excision
      is the treatment of choice, and recurrence is rarely encountered.

PMID- 12221391
TI  - Juvenile angiofibroma: report of a case with intraoral presentation.
AB  - We report a case of juvenile angiofibroma that presented as an ulcerative
      exophytic mass on the posterior hard palate of a 14-year-old male patient. The
      clinical features, diagnosis, and management of an extremely rare intraoral
      presentation of this benign lesion are reviewed.

PMID- 12221392
TI  - Apicomarginal defects in periradicular surgery: classification and diagnostic
      aspects.
AB  - The prognosis of periradicular surgery is affected by the amount and location of
      bone loss. Apicomarginal defects are localized bony defects encompassing the
      total root length, and periradicular surgery on these teeth is associated with a
      lower success rate. This paper reviews the etiology, pathogenesis, and morphology
      of apicomarginal defects as encountered in periradicular surgery on the basis of
      a series of 24 consecutively treated patients. Periodontal data were recorded
      before surgery in all patients, and apicomarginal defects were diagnosed after
      flap reflection or, if applicable, apicoectomy. On the basis of the findings in
      these cases and on theoretic considerations, a classification system for
      apicomarginal defects with potential therapeutic and prognostic implications is
      presented and several criteria for differential diagnosis are discussed.

PMID- 12221393
TI  - Substantive antimicrobial activity in chlorhexidine-treated human root dentin.
AB  - OBJECTIVE: The aim of this in vitro study was to assess the substantive
      antimicrobial activity of different medicaments in human root dentin. STUDY
      DESIGN: Canals of 98 roots were enlarged to standard size and medicated for 7
      days with the following: (1) 2% chlorhexidine (CHX) gel, (2) 0.2% CHX gel, (3) 2%
      CHX solution, (4) Ca(OH)(2), (5) Ca(OH)(2)+ 0.2% CHX gel, (6) 2% CHX solution + a
      25% CHX-containing controlled-release device, (7) saline, and (8) gel vehicle.
      After medication, canals were inoculated with Enterococcus faecalis for 21 days.
      Dentin samples were collected with Gates-Glidden burs into brain heart infusion
      broth, and bacterial growth was assessed with spectrophotometric analysis of
      optical density after 72 hours of incubation. RESULTS: Mean optical densities
      were significantly lower for groups with 2% CHX (1, 3, and 6) when compared with
      those of the controls (P < .05, analysis of variance with the Tukey test). Other
      groups did not differ significantly from the controls. CONCLUSIONS: Canal
      dressing for 1 week with 2% CHX may provide residual antimicrobial activity
      against E faecalis.

PMID- 12221394
TI  - Adenomatoid odontogenic tumor mimicking a periapical (radicular) cyst: a case
      report.
AB  - The adenomatoid odontogenic tumor (AOT) is a benign (hamartomatous), noninvasive
      lesion with slow but progressive growth. A rare subvariant of the extrafollicular
      type of AOT may mimic periapical disease radiographically. We report on a 15-year
      old girl with a periapical radiolucent lesion affecting teeth 7 and 8 initially
      suspicious of periapical disease, although clinical findings seemed to indicate a
      nonendodontic lesion. An exploratory surgical approach was chosen, and the final
      diagnosis of the removed noncystic tissue mass was microscopically confirmed to
      be an AOT.

PMID- 12221395
TI  - Response of autotransplanted teeth to electric pulp testing.
AB  - OBJECTIVE: The purpose of this retrospective study was to assess the results of
      third molar autotransplantation by using electric pulp testing (EPT) and to
      determine the correlation of EPT response and bone formation. STUDY DESIGN:
      Fourteen patients with 22 transplanted teeth were studied. The patients had
      received autotransplantation of third molars and regularly came for follow-up on
      the third, sixth, ninth, and twelfth months. Postoperative clinical assessment
      included pain, inflammation of surrounding soft tissues, tooth mobility, and the
      EPT response. Periapical radiographs were subsequently evaluated during follow
      up. The correlation between pulpal response to EPT and bone healing was analyzed.
      RESULTS: Most of the teeth had normal mobility within 3 months, which
      corresponded to bone formation. Bone healing at the recipient sites completely
      occurred within 6 months, and more than 50% had lamina dura. The teeth with EPT
      response increased to 95% within 12 months. There was no significant association
      between the EPT response and bone formation. CONCLUSIONS: The EPT response
      subsequently increased with time, and it seemed to be unchanged after 1 year.

PMID- 12221396
TI  - Solid-state nuclear magnetic resonance microscopy demonstrating human dental
      anatomy.
AB  - OBJECTIVE: Magnetic resonance imaging has become a common diagnostic tool in
      medical practice. It is a common view that solid-state material lacking a
      sufficient amount of unpaired nuclear spins, in particular proton spins, is
      impossible to depict with clinically used magnetic resonance devices.
      Characteristically rapid dephasing, caused by relatively short spin-spin
      relaxation (T(2) time) also leads to broad resonance lines. A newly introduced
      technique, constant-time imaging, uses 3 phase-encoding gradients for the
      acquisition of only one complex data point per phase-encoding step, resulting in
      detection times of only a few microseconds and extremely sharp resonance lines.
      STUDY DESIGN: Using a Bruker spectrometer AMX 300 WB (300 MHz, 7.1 T) with a
      microimaging attachment, we performed solid-state magnetic resonance imaging of
      whole teeth. Data processing was carried out by means of 3-dimensional Fourier
      analysis, and reconstructions were performed by the ParaVision (Bruker) software
      system. RESULTS: Dental hard tissues (enamel, dentin, and root cementum) and
      pulpal soft tissue could be depicted in 2-dimensional and 3-dimensional images.
      The voxel resolution isotropically reached 195 microm. CONCLUSION: The constant
      time imaging technique enabled a naturalistic and nondestructive visualization of
      the teeth without application of ionizing radiation. This technique bears the
      potential to help us overcome the limitations of clinically used standard
      magnetic resonance tomography devices and offers new perspectives for dental
      imaging.

PMID- 12221397
TI  - Temporomandibular joint and masticatory muscle involvement in myotonic dystrophy:
      a study by magnetic resonance imaging.
AB  - OBJECTIVE: The purpose of this study was to evaluate the masticatory muscles and
      the temporomandibular joint (TMJ) by magnetic resonance imaging (MRI) in myotonic
      dystrophy (MD) patients. STUDY DESIGN: MRI of the masticatory muscles and TMJ was
      performed in 15 MD patients, 11 male and 4 female, aged 16 to 53 years (mean, 31
      years). Many of them had dental malocclusion, especially Angle class III and
      anterior open bite, and 3 complained of recurrent TMJ dislocation. TMJ and
      masticatory muscle pain was not observed, and joint sounds were noted in only 1
      patient. RESULTS: The analysis of MRI scans showed masticatory muscle involvement
      in 13 patients (86.6%). In 11, the involvement was moderate to intense. The main
      abnormalities observed were increased intramuscular tissue signal on T1 (fatty
      infiltration) and volumetric reduction of muscles. Regarding the TMJ, articular
      disk displacement was seen in only 1 patient, but abnormalities of disk shape
      were common. Mild bone abnormalities were frequently observed, including changes
      of shape and contour of bone surface, and sclerosis of bone marrow. In 4 patients
      the condyle moved anterior to the eminence with the mouth opened fully (condylar
      hyperexcursion). CONCLUSIONS: This study shows that masticatory muscles are
      frequently and intensively affected in MD patients. Bone changes are the most
      consistent abnormalities observed in the TMJ. It is possible that remodeling is
      caused by biomechanical changes in the jaw as a result of masticatory muscle
      involvement.

PMID- 12221398
TI  - A comparative study of odontogenic keratocysts associated with and not associated
      with an impacted mandibular third molar.
AB  - OBJECTIVE: The purpose of this study was to compare odontogenic keratocysts
      associated with and not associated with an impacted mandibular third molar. STUDY
      DESIGN: Panoramic radiographs of odontogenic keratocysts associated with impacted
      mandibular third molars (15 cysts, associated group) were compared with
      radiographs of odontogenic keratocysts not associated with impacted mandibular
      third molars (25 cysts, nonassociated group). The radiographic images were
      analyzed with reference to the patients' age and sex. RESULTS: The mean age of
      patients in the associated group was lower than that of patients in the
      nonassociated group. The mean area of the cysts in the associated group was
      larger than that of those in the nonassociated group. The patients' ages did not
      significantly correlate to the areas of either kind of cyst. CONCLUSIONS: The
      odontogenic keratocysts in the associated group had a tendency toward rapid
      growth in the patients' youth.

PMID- 12221399
TI  - Intravenous myocardial contrast echocardiography predicts left ventricular
      remodeling in patients with acute myocardial infarction.
AB  - BACKGROUND: This study evaluated the ability of intravenous myocardial contrast
      echocardiography (MCE) performed in the setting of acute myocardial infarction
      for prediction of left ventricular (LV) remodeling. METHODS: Intravenous MCE was
      performed immediately before, 1 hour, and 24 hours after primary percutaneous
      transluminal coronary angioplasty (PTCA) in 35 patients with a first myocardial
      infarction. The MCE was used to define the relative perfusion defect size (in %;
      relMCD). Two-dimensional echocardiography was performed directly after
      angioplasty and after 4 weeks to determine LV end-diastolic volumes (LVEDV). The
      increase in LVEDV at 4 weeks defined a remodeling (> 15% increase) and a
      nonremodeling group (< or = 15% increase). RESULTS: Patients with remodeling had
      larger relMCD before (22.0 +/- 16.1 vs 8.0 +/- 11.9, P =.015), 1 hour (20.0 +/-
      13.0 vs 4.9 +/- 11.6, P =.001), and 24 hours after PTCA (22.9 +/- 14.1 vs 1.2 +/-
      2.8, P <.001). There was a significant correlation between relMCD 24 hours after
      PTCA and the increase in LVEDV at 4 weeks (r = 0.648; P <.001). Receiver
      operating characteristic (ROC) curve analysis revealed a relMCD at 24 hours of
      5.1% or more to predict remodeling with a sensitivity of 94% and a specificity of
      87% (area under ROC curve = 0.917; SE = 0.054). Multivariate analysis
      demonstrated relMCD at 24 hours to be the only predictor of remodeling (odds
      ratio = 173.4; P =.022). CONCLUSION: The size of the persistent MCE perfusion
      defect after revascularization for acute myocardial infarction has a high
      predictive value for LV remodeling during a 4-week follow-up period.

PMID- 12221400
TI  - Relation between myocardial oxygen consumption and myocardial blood volume: a
      study using myocardial contrast echocardiography.
AB  - Myocardial blood volume (MBV) is the volume of blood residing in myocardial
      vessels, 90% of which is in capillaries. MBV can be measured in vivo using
      myocardial contrast echocardiography (MCE). It has been shown that when increases
      in coronary blood flow (CBF) are not associated with increase in myocardial
      oxygen consumption (MVO(2)), MBV does not increase. We hypothesized that MBV
      would increase when increases in CBF are associated with an increase in MVO(2).
      The atrioventricular node was ablated in 18 dogs and dual-chamber pacing was
      instituted. In group 1 dogs (n = 9), heart rate was altered from 50 to 150 bpm(
      1) in increments of 20 bpm(-1) in random order. In group 2 dogs (n = 9), heart
      rate was kept constant, and dobutamine was infused at doses of 5, 10, 20, 30, and
      40 microg/kg(-1)/min(-1). During each intervention, hemodynamic parameters and
      MVO(2) were measured, and MCE was performed. MVO(2) increased more (P <.01) with
      inotropic compared with chronotropic stimulation, resulting in a parallel
      increase in CBF. MBV fraction and MCE-derived myocardial blood flow increased
      significantly with increases in MVO(2) (P <.05 and P <.001, respectively) when
      dobutamine was infused, but remained unchanged when heart rate alone was
      increased. We conclude that when MVO(2) is increased substantially, the resulting
      increase in CBF and MCE-derived myocardial blood flow is mediated, in part, by an
      increase in MBV. Thus, capillary recruitment plays an important role in the
      physiologic regulation of CBF. Lack of increase in MBV during dobutamine stress
      may indicate the presence of coronary stenosis or microvascular disease.

PMID- 12221401
TI  - The Tei index: a new prognostic index for patients with symptomatic heart
      failure.
AB  - BACKGROUND: The Tei index (TI) is a new echocardiographic/Doppler index of
      combined systolic and diastolic function, calculated as isovolumic relaxation
      time plus isovolumic contraction time divided by ejection time. This purpose of
      this study was to explore the prognostic value of TI in patients with heart
      failure from left ventricular (LV) systolic dysfunction. METHODS: Of 105 randomly
      selected participants with LV ejection fraction less than 30% and at least 1
      hospitalization for heart failure, we included 60 patients in whom assessment of
      the TI was technically feasible. Using the patients' medical records, we
      collected information on several clinical and echocardiographic variables. We
      monitored patients for a mean duration of 24 +/- 19 months from the time of the
      echocardiogram. The study outcome was the composite of death from any cause or
      emergency heart transplant. RESULTS: The median value (interquartile range) of TI
      was 0.79 (0.54, 1.14). Of 57 patients (95%) with complete follow-up, 28 (49%)
      died, and 2 (3.5%) underwent emergency heart transplant at a mean duration of 17
      +/- 14 months. Kaplan-Meier survival curves showed a higher cumulative incidence
      of the study end point among patients in the highest quartile of TI, compared
      with the other 3 quartiles (log rank P =.002). After adjustment for potential
      clinical confounders, TI in the highest quartile (TI > 1.14) was a significant
      independent predictor of the composite end point (odds ratio 5.3, 95% confidence
      interval 1.9 to 14.9, P =.0018). CONCLUSION: Prolonged TI (>1.14) is a powerful
      and independent predictor of poor clinical outcome in patients with symptomatic
      heart failure and severe LV systolic dysfunction.

PMID- 12221402
TI  - Severe aortic valve stenosis with preserved and reduced systolic left ventricular
      function: diagnostic usefulness of the Tei index.
AB  - BACKGROUND: In patients with severe aortic valve stenosis (AS), the onset of
      heart failure is associated with increased mortality and higher operative risk.
      Heart failure may result from either systolic, diastolic, or "overall" left
      ventricular dysfunction. The index "isovolumic contraction time and isovolumic
      relaxation time divided by ejection time" was shown to be a sensitive indicator
      of "overall" cardiac dysfunction in patients with dilated cardiomyopathy and
      cardiac amyloidosis. We sought to define the role of the Tei index in patients
      with severe AS and to validate this index against conventional measures of
      systolic and diastolic LV function. PATIENTS AND METHODS: Fifty-three
      participants underwent left heart catheterization for invasive measurement of LV
      end-diastolic pressure as a marker of diastolic function: 10 AS patients (valve
      orifice 0.6 +/- 0.2 qcm) with depressed systolic LV function (defined by LV
      ejection fraction < or = 45% [mean 32% +/- 8%], 7 male/3 female, 72 +/- 10 years
      old, DAS group), 22 AS patients (valve orifice 0.7 +/- 0.2 qcm) with preserved
      systolic LV function (ejection fraction > 45% [mean 55% +/- 6%], 13 male/9
      female, 71 +/- 11 years old, PAS group) and 21 asymptomatic control participants
      (ejection fraction > 45% [mean 62% +/- 8%], 14 male/7 female, 66 +/- 8 years old,
      CON group). Within 24 hours from catheterization, conventional 2-dimensional and
      Doppler echocardiographic examination including measurement of the Tei index was
      performed. RESULTS: LV end-diastolic pressure was elevated in the DAS and in the
      PAS group in comparison with control participants (32 +/- 6 mm Hg and 22 +/- 7 mm
      Hg vs 11 +/- 4 mm Hg, respectively, P <.01 for both comparisons). DAS patients
      were in a higher New York Heart Association functional class than PAS patients
      (3.2 +/- 0.4 vs 2.2 +/- 0.4, P <.001) The Tei index was easily and reproducibly
      obtained in all study participants. In the DAS group, isovolumic contraction time
      was prolonged and ejection time was shortened in comparison with the CON group
      (102 +/- 20 ms vs 52 +/- 15 ms, P <.01; and 235 +/- 44 ms vs 316 +/- 45 ms, P
      <.01), resulting in a significantly increased Tei index (0.78 +/- 0.28 vs 0.40 +/
      0.11, P <.01). In the PAS group, isovolumic relaxation time was shortened (62 +/
      18 ms vs 81 +/- 26 ms for the CON group, P <.01) and ejection time was prolonged
      (335 +/- 34 ms vs 316 +/- 45 ms for the CON group, P <.05), resulting in a
      decreased Tei index (0.29 +/- 0.12 vs 0.40 +/- 0.11, P <.05). Receiver operating
      characteristic curve analysis for the Tei index yielded an area under the curve
      of 0.98 +/- 0.03 for separating DAS and PAS patients. Using a Tei index greater
      than 0.42 as a cutoff, DAS patients were identified with a sensitivity of 100%
      and a specificity of 91%. CONCLUSION: The Tei index is significantly increased in
      patients with severe AS and depressed overall cardiac LV function. In AS patients
      with predominant diastolic dysfunction, in whom systolic function is preserved,
      the index is decreased in comparison with control patients. The index
      differentiates between symptomatic AS patients with depressed and less
      symptomatic AS patients with preserved systolic LV function, and may thus provide
      relevant information in the work-up and care of such patients.

PMID- 12221403
TI  - Effects of valve dysfunction on Doppler Tei index.
AB  - BACKGROUND: Recently proposed Doppler Tei index, defined as the sum of isovolumic
      contraction time or mitral valve closure to aortic valve opening time and
      isovolumic relaxation time or aortic valve closure to mitral valve opening time
      divided by ejection time, is a simple measure which enables noninvasive
      estimation of combined systolic and diastolic function and prediction of
      patients' prognosis. However, effects of valve dysfunction on Tei index have not
      been investigated. This study was designed to compare Tei index before and after
      surgical valve replacement or repair to evaluate effects of valve dysfunction on
      Tei index. METHODS: Participants consisted of 76 consecutive patients with aortic
      or mitral valve surgery (26 patients with aortic stenosis [AS], 16 with aortic
      regurgitation, 17 with mitral stenosis, and 17 with mitral regurgitation).
      Doppler Tei index was evaluated before and after the surgery by obtaining (a
      b)/b, where a is the interval between the cessation and onset of Doppler mitral
      filling flow and b is the aortic flow ejection time. RESULTS: Tei index
      significantly increased after surgery in patients with AS (0.38 +/- 0.07 to 0.49
      +/- 0.06, P <.001), aortic regurgitation (0.60 +/- 0.20 to 0.70 +/- 0.18, P
      <.01), mitral stenosis (0.34 +/- 0.03 to 0.39 +/- 0.04, P <.01), and decreased
      with no significance in mitral regurgitation (0.50 +/- 0.03 to 0.46 +/- 0.03).
      Percent change in Tei index after valve surgery was maximal in patients with AS
      (27 +/- 6 vs 17 +/- 2 vs 16 +/- 6 vs -9% +/- 6%, AS vs aortic regurgitation vs
      mitral stenosis vs mitral regurgitation, P <.001). CONCLUSION: Tei index
      significantly changes after valve surgery especially in patients with AS.
      Considerations for the effects of valve dysfunction on Tei index are required for
      its application to evaluate ventricular function in patients with valve disease.

PMID- 12221404
TI  - The role of Doppler left ventricular filling indexes and Doppler tissue
      echocardiography in the assessment of cardiac involvement in hereditary
      hemochromatosis.
AB  - Although cardiac dysfunction in hereditary hemochromatosis (HHC) can be evaluated
      by conventional echocardiography, findings are often not specific. To test the
      hypothesis that the assessment of (1) conventional Doppler left ventricular
      filling indexes and (2) intrinsic elastic properties of the myocardium by Doppler
      tissue echocardiography can both enhance the accuracy of echocardiographic
      diagnosis of cardiac involvement in HHC, a group of 18 patients with HHC (mean
      age 50 +/- 17 years) and 22 age-matched healthy subjects were studied. The
      following indexes were characteristic for HHC: (1) the duration of atrial
      reversal measured from pulmonary venous flow (ms) was longer (118 +/- 20 vs 90 +/
      16; P <.001); (2) systolic lateral mitral, early-diastolic medial mitral, and
      early-diastolic lateral tricuspid annular velocities were reduced by 23%, 31%,
      and 13%, respectively; (3) late-diastolic mean myocardial velocity and myocardial
      velocity gradient (MVG) were also reduced by 22% and 34%, respectively. Late
      isovolumic relaxation (late-IVR) MVG (s(-1)) was positive in HHC as opposed to
      negative in healthy subjects (1.72 +/- 0.85 vs -0.89 +/- 1.15; P <.001)
      indicating impaired early-diastolic subepicardial relaxation in HHC. The
      assessment of atrial reversal flow duration, the difference in duration between A
      wave and atrial reversal flow, and the presence of positive late IVR-MVG findings
      were the most accurate variables to differentiate patients with HHC from healthy
      subjects (80%, 67%, 94% sensitivity and 90%, 95%, 86% specificity, respectively).

PMID- 12221405
TI  - Pulsed Doppler tissue imaging in dystrophinopathic cardiomyopathy.
AB  - Cardiac dysfunction is a primary feature in patients and female carriers of
      Becker muscular dystrophy (BMD). Conventional echocardiography and pulsed Doppler
      tissue imaging (DTI) were performed in 28 patients with BMD, in 20 female
      carriers, and in 38 control participants (20 men and 18 women). Left ventricular
      ejection fraction (LVEF) was lower in BMD patients (P <.02) and carriers (P <.02)
      than in normal participants. Two subgroups of BMD patients were identified: A1 =
      LVEF > or = 55% (n = 20) and A2 = LVEF < 55% (n = 8). The carriers displayed LVEF
      > or = 55%. Compared with control participants the diastolic alterations by
      conventional echocardiography were lower early filling peak in the subgroup A1 (P
      <.05) and prolonged isovolumic relaxation time in A1, A2, and in carriers (at
      least P <.02). Furthermore, pulsed DTI showed lower early diastolic wave peak at
      basal septum in A2 (P <.05) and in carriers (P <.0001); at lateral mitral annulus
      and at basal inferior wall in A1, A2, and in carriers (at least P <.05); lower
      early/late diastolic wave ratio at basal septum and lateral mitral annulus (P
      <.05) in carriers; and prolonged isovolumic relaxation time in A1, A2, and in
      carriers (at least P <.02), except at lateral mitral annulus of carriers.
      Systolic parameters investigated by pulsed DTI detected lower peak systolic wave
      at basal septum in A1, A2, and carriers (P <.02); at lateral mitral annulus in
      carriers (P <.02); at basal inferior wall in A1, A2 (P <.02), and in carriers (P
      <.0001); and lower time-velocity integral of S wave at each segment in A1, A2,
      and in carriers. In dystrophinopathic cardiomyopathy, pulsed DTI may be a useful
      technique to assess diastolic dysfunction and appears to be a promising tool in
      identifying early regional systolic alterations in patients and carriers with
      normal LVEF.

PMID- 12221406
TI  - Assessment of regional systolic and diastolic wall motion velocities in highly
      trained athletes by pulsed wave Doppler tissue imaging.
AB  - We studied the relationship between left ventricular (LV) function and the
      increased LV mass in 18 highly trained rowing athletes (14 men, 4 women; mean age
      20.7 +/- 4.5 years) using pulsed wave Doppler tissue imaging (PWDTI). Thirteen
      untrained volunteers, matched for age and body mass index, acted as control
      participants. Peak systolic, early diastolic (Ev), and late diastolic (Av)
      myocardial velocities (cm/s); Ev/Av ratio; and isovolumic relaxation time (ms)
      were measured at the level of basal lateral wall and basal posterior
      interventricular septum (bas-IVS) segments. In comparison with control
      participants, athletes showed a greater LV cavity size (P <.05), wall thickness
      (IVS, P <.001; posterior wall, P <.01), and mass index (P <.001). In athletes,
      systolic velocity of bas-IVS had increased (P <.001) and was positively
      correlated with IVS thickness (r = 0.66, P <.005) and LV mass index (r = 0.71, P
      <.001). Of the PWDTI-measured diastolic indexes, Ev/Av ratio significantly
      increased in athletes in comparison with control participants in both the
      examined segments (bas-IVS, P <.05; basal lateral wall, P <.05). When Ev and Av
      were separately considered, a different behavior was found in the 2 segments: Ev
      significantly increased in the basal lateral wall (P <.005); Av significantly
      decreased in the bas-IVS. The increase in the systolic velocity of bas-IVS
      suggests that septum greatly contributes to the longitudinal LV systolic
      shortening and increase of stroke volume in athletes compared with untrained
      participants. Moreover, the behavior of PWDTI diastolic velocities suggests a
      more effective relaxation activity in the longitudinal axis at the level of
      lateral wall. This study suggests therefore the usefulness of PWDTI in the
      assessment of functional properties of "athlete's heart" and differentiation from
      pathologic cardiac conditions.

PMID- 12221407
TI  - Longitudinal motion of the atrioventricular annuli in children: reference values,
      growth related changes, and effects of right ventricular volume and pressure
      overload.
AB  - The goals of this study were to characterize normal patterns of longitudinal
      motion of atrioventricular annuli in the young, establish reference values and
      assess growth-related changes (n = 40). Sensitivity to changes in right
      ventricular volume and pressure load was assessed in patients with atrial septal
      defect (ASD) (n = 25) and with primary pulmonary hypertension (PPH) (n = 20). M
      mode of the annuli were obtained from apical views. In healthy subjects,
      longitudinal %displacement decreased with growth, lateral tricuspid annulus had
      highest %displacement, velocity of annular descent did not change with growth,
      tricuspid lateral annulus had the highest velocity of descent, only ascent
      velocity of the lateral tricuspid annulus decreased with growth, velocities of
      ascent for the lateral annuli were similar and higher than the septum, and heart
      rate had no effect on parameters tested. In patients with ASD, the findings were
      an exaggerated normal pattern. In patients with PPH, %displacement and ascent
      velocities were blunted. Our results demonstrate the utility of this technique to
      assess annular dynamics in pediatric patients.

PMID- 12221408
TI  - Echocardiography after cardiac transplantation.

PMID- 12221409
TI  - Improvement in echocardiographic evaluation of left ventricular wall motion using
      still-frame parametric imaging.
AB  - BACKGROUND: Conventional echocardiographic assessment of left ventricular wall
      motion is based on visual interpretation of dynamic images, which depends on
      readers' experience. We tested the feasibility of evaluating endocardial motion
      using still-frame parametric images. METHODS AND RESULTS: In protocol 1,
      integrated backscatter images were obtained in 8 anesthetized pigs at baseline,
      5, and 60 seconds after left anterior descending coronary occlusion and during
      reperfusion. Images from 1 cardiac cycle were analyzed offline to create a
      parametric image of local video intensity oscillations. Ischemia-induced changes
      were quantified by segmenting the parametric images and calculating regional
      pixel-intensity profiles. In protocol 2, parametric images were obtained from
      contrast-enhanced echocardiograms in 30 patients (18 with wall-motion
      abnormalities; 12 control subjects). "Gold standard" for wall motion was
      determined from independent interpretations of dynamic images made by 3
      experienced reviewers. Dynamic images were independently classified by 3
      inexperienced and 3 intermediate-level readers. Interpretation was then repeated
      in combination with parametric images. Parametric images showed a bright band in
      the area spanned by endocardial motion, which gradually decreased in brightness
      and thickness in the left anterior descending territory during coronary occlusion
      in all animals. In patients, the agreement with the gold standard correlated with
      the readers' experience (68% inexperienced, 87% intermediate) and significantly
      improved by adding parametric images (83% and 91%, respectively). CONCLUSION:
      Parametric imaging provides a still-frame display of regional endocardial motion,
      sensitive to track ischemia-induced abnormalities. When combined with dynamic
      images, this technique improves the accuracy of the interpretation of wall
      motion, especially by less experienced echocardiographers.

PMID- 12221411
TI  - Correlation between measured inferior vena cava diameter and right atrial
      pressure depends on the echocardiographic method used in patients who are
      mechanically ventilated.
AB  - In patients who are mechanically ventilated, the correlation between inferior
      vena cava diameter (IVCD) measurements and mean right atrial pressure (RAP)
      varies in the literature. The purpose of this study was to test if the
      correlation between IVCD and RAP measurement in patients who are critically ill
      depends on the transthoracic echocardiography (TTE) methodology used. Twenty
      patients who were critically ill, sedated, and required respiratory support were
      prospectively studied by TTE during mechanical ventilation in a controlled mode.
      The TTE measures of IVCD were made, using methods previously cited. First, IVCD
      was measured at end-expiration and end-diastole, with ECG synchronization, using
      the M-mode, on short-axis view 2 cm below the right atrium. Second, IVCD was
      assessed at end-expiration, without ECG synchronization, using the 2-dimensional
      long-axis view at the same location. RAP was measured simultaneously by using a
      central venous catheter positioned in the superior vena cava. All measurements
      were taken in the supine position. IVCD at end-expiration and end-diastole, with
      ECG synchronization, using the M-mode, and IVCD at end-expiration, without ECG
      synchronization, using the 2-dimensional long-axis view, correlate linearly with
      RAP (0.81, P <.0001 and 0.71, P =.0004). Mean bias between the 2 TTE methods
      (Bland-Altman analysis) was 1.6 mm (SD +/- 2.03 mm). In conclusion, this study
      confirms that variation of correlation between TTE IVCD measurement and RAP
      depends on the ultrasonographic methodology used and the timing of measurement
      during the cardiac cycle. IVCD at end-expiration and end-diastole, with ECG
      synchronization, using the M-mode (IVCD-MM) correlates more satisfactory with RAP
      than with IVCD at end-expiration, without ECG synchronization, using the 2
      dimensional long-axis view, in patients during mechanical ventilation.

PMID- 12221410
TI  - Can left ventricular diastolic stiffness be measured noninvasively?
AB  - BACKGROUND: A noninvasive estimation of left ventricular (LV) diastolic chamber
      stiffness (K(LV)) is still a challenge. Experimental data suggests that K(lv) can
      be obtained by using Doppler mitral flow deceleration time (DT) as the only
      variable: K(lv) = (70/[DT-20])(2) mm Hg/mL. We assessed the accuracy of this
      noninvasive estimate of K(lv) by comparing it with invasive measurement of K(lv)
      in intact patients with a wide range of LV size and function under varying
      loading conditions. METHODS: Twenty-five patients (age 54 +/- 12 years) with
      ischemic heart disease (n = 19) or primary LV dysfunction (n = 6), with a wide
      range of DT (79-324 ms) and ejection fraction (8%-57%), underwent simultaneous
      assessment of LV pressure by micromanometer and volume by 2-dimensional (2D)
      echocardiography-guided Doppler mitral flow velocity (where volume = mitral flow
      velocity integral x annular area) calibrated to 2D echocardiography stroke
      volume. Invasive K(lv) [delta pressure (from minimum to end-diastolic)/delta
      volume (during the same time interval)] was obtained at baseline and in 23
      patients after LV unloading by prostaglandin E(1) (30-60 ng/kg/min) (n = 12),
      nitroglycerin (0.2 mg) (n = 9) or magnesium (1 g) (n = 2). Noninvasive K(lv) was
      estimated according to the above formula. RESULTS: In this set of patients with
      normal mitral annular area (3.9 +/- 1.1 cm(2)/m(2)), multivariate analysis showed
      that DT is inversely related to K(lv) (P <.001) but not to left atrial chamber
      stiffness, LV volume, relaxation time constant, mitral valve opening pressure, or
      area. The relation between noninvasively calculated and directly measured K(lv)
      was close to the line of identity under all conditions, (y = 0.93x + 0.05, r =
      0.67, n = 48, P <.001), although with a wide standard error of the estimate (0.26
      mm Hg/mL). CONCLUSION: We conclude that K(lv) can be calculated +/- 0.5 mm Hg/mL
      from noninvasively measured DT in patients.

PMID- 12221412
TI  - Intraoperative transesophageal echocardiography accurately predicts mitral valve
      anatomy and suitability for repair.
AB  - Mitral valve (MV) repair is the procedure of choice for MV prolapse or flail.
      However, valve repair is more technically demanding and requires a precise
      definition of MV morphology to determine the timing, complexity, and feasibility
      of repair. We prospectively examined 170 consecutive patients with MV prolapse or
      flail referred for MV repair. The MV valve was systematically assessed by
      intraoperative transesophageal echocardiography. MV anatomy was independently
      assessed at the time of operation. Accuracy of transesophageal echocardiography
      in identifying MV segments ranged from 90% to 97%, and was best for the middle
      segment/scallop of either anterior or posterior leaflet. MV repair was successful
      in 91% of patients. Success rate was the lowest (78%) in the presence of
      extensive bileaflet disease involving at least 2 segments of each leaflet.
      Independent predictors of unsuccessful repair were central jet of mitral
      regurgitation, calcification or severe dilatation of the mitral annulus, and
      extensive leaflet disease with involvement of at least 3 segments.

PMID- 12221413
TI  - Contrasting effect of similar effective regurgitant orifice area in mitral and
      tricuspid regurgitation: a quantitative Doppler echocardiographic study.
AB  - We compared the effect of similar effective regurgitant orifice (ERO) areas in
      tricuspid regurgitation (TR) and mitral regurgitation (MR) on hemodynamics and
      volume overload, and examined the impact on grading of TR and MR severity. In a
      prospective study, 95 patients with TR in sinus rhythm were compared with 95
      patients with MR in sinus rhythm matched for ERO area, age, and body surface
      area. We found that similar ERO area was associated with decreased volume
      overload in TR compared with MR. There were more women with TR than with MR, but
      comparison stratified by sex confirmed that regurgitant volume (RVol) was smaller
      in TR than in MR for similar ERO area. However, patients with systolic venous
      flow reversal (hepatic for TR and pulmonary for MR) had lower RVol but similar
      ERO area in TR compared with MR. Therefore, optimal diagnostic thresholds for
      severe regurgitation (maximum sum of sensitivity and specificity) in TR and MR
      were different for RVol (45 and 60 mL/beat, respectively) but similar for ERO
      area (40 mm(2)). We conclude that similar ERO areas induce less RVol in TR than
      in MR because of the decreased driving force in TR, but have similar consequences
      with regard to venous flow reversal. Therefore, a similar ERO area grading scheme
      can be used, and an ERO area of 40 mm(2) or greater is consistent with severe
      regurgitation in both TR and MR.

PMID- 12221414
TI  - Quantitative analysis of aortic regurgitation: real-time 3-dimensional and 2
      dimensional color Doppler echocardiographic method--a clinical and a chronic
      animal study.
AB  - BACKGROUND: For evaluating patients with aortic regurgitation (AR), regurgitant
      volumes, left ventricular (LV) stroke volumes (SV), and absolute LV volumes are
      valuable indices. AIM: The aim of this study was to validate the combination of
      real-time 3-dimensional echocardiography (3DE) and semiautomated digital color
      Doppler cardiac flow measurement (ACM) for quantifying absolute LV volumes, LVSV,
      and AR volumes using an animal model of chronic AR and to investigate its
      clinical applicability. METHODS: In 8 sheep, a total of 26 hemodynamic states
      were obtained pharmacologically 20 weeks after the aortic valve noncoronary (n =
      4) or right coronary (n = 4) leaflet was incised to produce AR. Reference
      standard LVSV and AR volume were determined using the electromagnetic flow method
      (EM). Simultaneous epicardial real-time 3DE studies were performed to obtain LV
      end-diastolic volumes (LVEDV), end-systolic volumes (LVESV), and LVSV by
      subtracting LVESV from LVEDV. Simultaneous ACM was performed to obtain LVSV and
      transmitral flows; AR volume was calculated by subtracting transmitral flow
      volume from LVSV. In a total of 19 patients with AR, real-time 3DE and ACM were
      used to obtain LVSVs and these were compared with each other. RESULTS: A strong
      relationship was found between LVSV derived from EM and those from the real-time
      3DE (r = 0.93, P <.001, mean difference (3D - EM) = -1.0 +/- 9.8 mL). A good
      relationship between LVSV and AR volumes derived from EM and those by ACM was
      found (r = 0.88, P <.001). A good relationship between LVSV derived from real
      time 3DE and that from ACM was observed (r = 0.73, P <.01, mean difference = 2.5
      +/- 7.9 mL). In patients, a good relationship between LVSV obtained by real-time
      3DE and ACM was found (r = 0.90, P <.001, mean difference = 0.6 +/- 9.8 mL).
      CONCLUSION: The combination of ACM and real-time 3DE for quantifying LV volumes,
      LVSV, and AR volumes was validated by the chronic animal study and was shown to
      be clinically applicable.

PMID- 12221415
TI  - Three-dimensional transesophageal echocardiography in tumors of the heart.
AB  - Three-dimensional echocardiography was used to study 5 women, 4 with intracardiac
      tumors and 1 with a paracardial neoplasia. Three-dimensional transesophageal
      echocardiography was found to be a valuable way to define the morphologic and
      spatial characteristics of cardiac and paracardial tumors in vivo, establish
      their relationships with adjacent structures, and assess the hemodynamic effects
      they can produce.

PMID- 12221416
TI  - Sedation for pediatric echocardiography: evaluation of preprocedure fasting
      guidelines.
AB  - In an effort to increase the safety of sedated procedures, there is a recent
      trend to increase preprocedure fasting times. However, optimal fasting times have
      never been established for a sedated echocardiogram. We retrospectively analyzed
      334 patients divided into 2 groups. Group 1 (140 patients) had fasting times less
      than 2 hours, whereas group 2 (184 patients) had fasting times more than 2 hours.
      When the entire population was considered, there was no difference in efficacy
      between the 2 groups (P =.08). However, in patients younger than 6 months, group
      2 had decreased efficacy compared with group 1 (P =.03). There were no major
      complications in either group. There was no difference in the rate of minor
      complications between the 2 groups. Our study concludes that longer fasting times
      are less efficacious in children younger than 6 months, and do not improve
      safety.

PMID- 12221417
TI  - Assessment of coronary flow reserve by adenosine transthoracic echocardiography:
      validation with intracoronary Doppler.
AB  - OBJECTIVE: Data on the accuracy of transthoracic echocardiographic (TTE) analysis
      of coronary flow reserve are scarce. We compared coronary flow reserve
      measurements assessed using TTE with those achieved using the gold standard of
      intracoronary Doppler. METHODS: Twenty-one patients admitted for elective
      coronary angioplasty to the circumflex or left anterior descending (LAD) coronary
      artery underwent TTE immediately before angioplasty, both at rest and during
      intravenous administration of adenosine 140 microg/kg/min. Transthoracic images
      of distal LAD coronary diameter and coronary flow were obtained in 14 patients
      (66%). These patients then underwent intracoronary Doppler analysis of coronary
      flow reserve in the distal LAD coronary artery. In 1 patient with a proximal LAD
      artery lesion, the narrowing could not be crossed with the Doppler guidewire.
      Paired data on coronary flow reserve were therefore available in 13 patients.
      RESULTS: Patients were aged 61.7 +/- 8.3 years. Ten were men. Body mass index was
      26.3 +/- 4.6 kg/m(2). Resting distal LAD artery blood flow was 18.4 +/- 9.0
      mL/min assessed by TTE versus 17.6 +/- 8.1 mL/min by intracoronary Doppler.
      Hyperemic flow was 36.3 +/- 23.4 versus 33.1 +/- 19.2 mL/min, respectively.
      Coronary flow reserve was therefore 1.89 +/- 0.66 by TTE compared with 1.83 +/-
      0.62 by intracoronary Doppler. Limits of agreement for coronary flow reserve were
      -0.28 to +0.44, well within boundaries of clinical acceptability. CONCLUSION:
      Transthoracic echocardiography is capable of providing accurate data on coronary
      flow reserve in the distal LAD coronary artery. As a truly noninvasive modality,
      this technique offers advantages over traditional invasive procedures.

PMID- 12221418
TI  - Echocardiographic diagnosis of coronary sinus ostial atresia.
AB  - Coronary sinus ostial atresia is a rare anomaly that can result in serious
      hemodynamic sequelae if the decompressing vessel is occluded. Echocardiographic
      recognition of this malformation in patients with coexistent congenital heart
      disease before catheterization or surgical intervention may prevent occlusion of
      the decompressing left superior vena cava.

PMID- 12221419
TI  - Bicuspid aortic valve stenosis complicated by descending aortic dissection
      mimicking coarctation of the aorta.
AB  - We report a rare case of bicuspid aortic stenosis complicated by an ascending
      aortic aneurysm and aortic dissection of DeBakey type IIIb. A 35-year-old woman
      was admitted to our hospital to examine her systolic murmur identified at birth.
      Severe aortic stenosis, dilatation of the ascending aorta, and the narrow color
      flow signal in the descending aorta were detected by transthoracic
      echocardiography. Initially, coarctation of the descending aorta was suspected,
      but aortic dissection, DeBakey type IIIb, was revealed by transesophageal
      echocardiography. Transesophageal echocardiography is indicated when only
      insufficient information is available on valve and aortic morphology in patients
      with bicuspid aortic valve.

PMID- 12221420
TI  - An unusual case of partial anomalous pulmonary venous drainage.
AB  - We report a case of partial anomalous pulmonary venous drainage where the left
      upper and lower pulmonary veins drain into a separate posterior left atrial (LA)
      chamber before continuing as a vertical ascending vein. The vertical vein then
      joins the left innominate vein, which eventually drains into a normal right-sided
      superior vena cava. There was no fenestration or communication between this
      posterior chamber and the true LA. The true LA contained the fossa ovale and LA
      appendage. The right upper and lower pulmonary veins drain normally into the true
      LA. To our knowledge, this is the first case where the left upper and lower
      pulmonary veins drain into a separate posterior LA chamber before continuing into
      a vertical vein. The diagnosis was initially made with transesophageal
      echocardiography and confirmed by magnetic resonance imaging. The patient later
      underwent successful corrective operation.

PMID- 12221421
TI  - Cardiac tamponade masking clinical presentation and hemodynamic effects of
      papillary muscle rupture after acute myocardial infarction.
AB  - A 67-year-old woman sustained an acute lateral-wall myocardial infarction and was
      treated with thrombolytic therapy. Postinfarction hypotension developed 3 days
      later. Clinical findings at that time were consistent with cardiac tamponade, and
      an echocardiographic study revealed a moderate-sized pericardial effusion. She
      underwent urgent pericardiocentesis with transient improvement in hemodynamics,
      followed by deterioration associated with the development of acute pulmonary
      edema. Follow-up transesophageal echocardiographic imaging revealed papillary
      muscle rupture with severe mitral regurgitation. The patient underwent urgent
      surgical intervention consisting of coronary artery bypass grafting and mitral
      valve replacement. The presence of cardiac tamponade in this patient masked the
      clinical manifestations of papillary muscle rupture through the hemodynamic
      effect of tamponade physiology on mitral regurgitation.

PMID- 12221422
TI  - Usefulness of the transgastric view by transesophageal echocardiography in
      evaluating thickened pericardium in patients with constrictive pericarditis.
AB  - Detection of thickened pericardium in patients with constrictive pericarditis is
      essential for pericardiectomy because restrictive cardiomyopathy and severe
      tricuspid regurgitation show similar hemodynamic data. The purpose of this study
      was to clarify whether transesophageal echocardiography can evaluate thickened
      pericardium. We investigated 7 patients with constrictive pericarditis who
      underwent pericardiectomy. Thickened pericardium over the right atrium was
      detected in 6 patients, but the borders were not clear. Thickened pericardium
      over the left ventricle was not detected in any patients in the standard
      longitudinal and horizontal views. On the other hand, thickened pericardium over
      the ventricles was detected in all patients in the transgastric view as an
      echogenic area between the liver and ventricular wall. Tissue characteristics of
      the thickened pericardium could be evaluated because of the high-quality images
      in the transgastric view. The transgastric view by transesophageal
      echocardiography allows high-quality images of the pericardium, which might be
      useful in diagnosing constrictive pericarditis.

PMID- 12221423
TI  - Left cavities spontaneous contrast opacification.
AB  - We report a transesophageal echocardiography study of a patient in a critical
      care unit under mechanical respiratory assistance in whom left cavities
      spontaneous contrast opacification was seen, suggesting systemic gas embolism as
      the probable mechanism.

PMID- 12221424
TI  - Intrapulmonary arteriovenous shunt: diagnosis by saline contrast bubbles in the
      pulmonary veins.
AB  - A 54-year-old man with end-stage cirrhosis of the liver presented for evaluation
      of dyspnea. Intrapulmonary arteriovenous shunting was suspected. Transthoracic
      echocardiography with agitated saline contrast injection from the right
      antecubital vein was performed. Late arrival of saline contrast bubbles in the
      left atrium by pulmonary veins leading to complete left heart opacification
      confirmed the diagnosis of significant intrapulmonary shunting. This case and
      images illustrate the use of agitated saline contrast in combination with
      transthoracic echocardiography for the diagnosis of intrapulmonary arteriovenous
      fistula.

PMID- 12221425
TI  - Detection of intracoronary air embolism by echocardiography.
AB  - We report the diagnosis of intracoronary air embolism by transesophageal
      echocardiography in 2 patients undergoing open heart surgery. The sudden
      appearance of inferior wall akinesis with increased brightness of the area
      immediately after removal of the aortic cross clamp and spontaneous resolution of
      the abnormalities support the diagnosis of intracoronary air embolism.

PMID- 12221426
TI  - Left atrial free floating ball thrombus in hypertrophic cardiomyopathy: a case
      report.
AB  - In this article we reported a 33-year-old female patient who was referred to our
      emergency department with atrial fibrillation, congestive heart failure, and
      cardiogenic shock. In her transthoracic echocardiography, a free-floating ball
      type mass was seen in the left atrial cavity with a hypertrophic cardiomyopathy.
      An emergency open-heart surgery was performed. The mass was removed, and
      pathologic examination confirmed the thrombotic material.

PMID- 12221427
TI  - Thrombus-in-transit and paradoxical embolism.
AB  - Paradoxical embolism is an uncommon but clinically important phenomenon. Elements
      of diagnosis include the presence of: (1) a venous thrombus, (2) an arterial
      embolus, (3) a communication between the right and left heart, and (4) a thrombus
      traversing such a communication. Unfortunately, all of these elements can be
      rarely demonstrated in each case but the probability should be considered in any
      patient with 2 or more present. It should be suspected in patients who have
      evidence of systemic arterial emboli without apparent cause. A transesophageal
      echocardiogram with contrast should be considered in cases where paradoxical
      embolism is a possibility. We present a case in which a "thrombus-in-transit" was
      imaged across the interatrial septum in a patient with a patent foramen ovale,
      deep venous thrombosis, and an embolic cerebrovascular stroke.

PMID- 12221428
TI  - Spontaneous closure (thrombosis) of the intramyocardial dissection: 40-month
      follow-up.
AB  - Intramyocardial dissection is an uncommon complication of a myocardial infarction
      or blunt chest trauma created by a hematoma located between the layers of
      myocardial fibers. This report describes the clinical course, 2-dimensional, and
      3-dimensional echocardiographic findings of an unusual case of the
      intramyocardial dissection.

PMID- 12221429
TI  - Traumatic aneurysm and pseudoaneurysm of the right ventricle: a diagnosis by
      echocardiography.
AB  - We report a case of a rare aneurysm of the right ventricular outflow tract, and a
      pseudoaneurysm of the right ventricle caused by a remote motor vehicle accident.

PMID- 12221430
TI  - Intracardiac echocardiography in the detection of pacemaker lead endocarditis.
AB  - At times, infection of pacemaker leads can be difficult to confirm even with
      transesophageal echocardiography. We describe a patient with pacemaker lead
      infection where the transesophageal echocardiogram was nondiagnostic, and
      intracardiac echocardiography made the diagnosis by demonstrating the vegetation
      on the pacemaker lead. This illustrates a potential role for intracardiac
      echocardiography in infective endocarditis when transesophageal echocardiography
      is nondiagnostic.

PMID- 12221432
TI  - [NEW CONCEPTS IN C VIRUS HEPATITIS]

PMID- 12221431
TI  - Validation of the Doppler PR interval in the fetus.

PMID- 12221433
TI  - [ENDOSCOPIC INJECTION TREATMENT OF BLEEDING PEPTIC ULCER]
AB  - BACKGROUND: Objectives were two. (1) to determine theefficiency of the endoscopic
      injection therapy (EIT) in patients suffering from bleeding caused by peptic
      ulcer disease with high risk of recurrence, and (2) to recognize clinical and
      endoscopical risk factors that influence recurrence of hemorrhage and mortality
      from this pathology. METHODS: This is a retrospective study that included 121
      patients, who were admitted by a unit specialized in managing gastrointestinal
      hemorrhage owing to peptic ulcer with active bleeding or non-bleeding visible
      vessel, and who underwent EIT with epinephrine between March, 1994 and February,
      1996.RESULTS: Initial success was achieved in 119 patients who underwent EIT
      (99,1%). Bleeding persisted in one patient (0,9%), and in another one, EIT was
      not sucessful because of inaccessible location. Definite hemostasis was achieved
      in 93 patients (77,5%) and there was recurrence in 28 cases (23,5%). Twenty-six
      patients underwent surgical therapy (21,5%). The univariable analysis showed that
      hemorrhage recurrence was related to the presence of shock (p = 0,002),
      hematemesis (p = 0,2), age over 60 (p = 0,009), number of blood units transfused
      (p = 0,00000) and ulcer diameter larger than 2 cm (p = 0,018). The global
      mortality in our patients was of 10%, and surgical mortality was of 34,6%.
      Factors significantly related to mortality were hemorrhage recurrence (p =
      0,000003), presence of concomitant disease (p = 0,05), and presence of gastric
      ulcer (p = 0,021), in addition to age (over 60), presence of shock and ulcer
      diameter larger than 2 cm (p = 0,05).CONCLUSION: EIT is a valuable procedure for
      the treatment of hemorrhage caused by peptic ulcer with high risk of recurrence
      (active hemorrhage or visible vessel), with a definite hemostasis of 77,5%. The
      presence of shock, hematemesis, age over 60, transfusion requirements of more
      than 3 blood units, and ulcer diameter of more than 2 cm are factors that
      increase the probability of hemorrhage recurrence after EIT. Mortality is
      significantly related to the presence of hemorrhage recurrence, concomitant
      diseases and gastric ulcer in addition to clinical and endoscopical factors
      mentioned above, with the exception of hematemesis and transfusion requirement. A
      prompt surgery after detection of a major bleeding recurrence in patients with
      the risk factor already described and a coordinate action with a surgery team
      experienced in digestive hemorrhage would influence favorably the mortality rate
      of this disease.

PMID- 12221434
TI  - [ENDOSCOPIC TREATMENT OF UPPER GASTROINTESTINAL BLEEDINGCAUSED BY PEPTIC ULCER]
AB  - Upper digestive bleeding (UDB) owing to peptic ulcer, 52 Forrest I and 116
      Forrest II, was studied prospectively in 168 patients. Therapeutic endoscopy was
      performed to those patients at the Endoscopic Surgery Center of the "General
      Calixto Garcia" Hospital during a period of 13 months, beginning on December,
      1995. Different hemostatic methods, chosen at random, were used for determining
      their efficacy in bleeding control and therefore, reducing lethality, mortality,
      hospitalization time and others. Chi-square and f-Fischer tests were applied
      through the STATGRAPHICS 4,0 package for statistical analysis. Immediate
      hemostatic efficacy was obtained in 97,8%, not existing significant statistical
      differences between the methods used for bleeding control. Recurrent hemorrhage
      ocurred in 13,1%. Mean hospitalization time was 7,19 days and the most frequent
      hospitalization time (mode) was just 3 days. The average amount of blood units
      transfused was 2,87. Surgery was required by 9,5% of patients and just 2,9% were
      urgent cases due to hemorrhage. Lethality owing to bleeding was 1,8%, and
      mortality was 0,23%. This experimental group was compared with a historic control
      group composed of 404 patients who received conventional treatment for UDB owing
      to peptic ulcer from 1991 to 1993 in Militar Hospital "Carlos J. Finlay". Mean
      hospitalizacion time blood units transfused was 5,9 (according to the medical
      information available for this kind of treatment). Surgery was required by 27,2%
      of patients. Lethality was 9,9% and mortality was 1.5%. Comparing results
      obtained in both groups through statistial methods, the abatement of mortality,
      lethality, mean hospitalization time, transfused blood consumption, and emergency
      surgeries due to hemorrhage is highly significant.

PMID- 12221435
TI  - [GASTROINTESTINAL INVOLVEMENT IN HUMAN BARTONELLOSIS]
AB  - We present a prospective study of 68 patients with the acute phase of human
      bartonellosis, admitted to Cayetano Heredia National Hospital.Gastrointestinal
      symptoms were reported as follows: abdominal pain 46,3%, coluria 44,4%, vomiting
      40,3%, jaundice 38,5%, diarrhea 29,9%, constipation 8,9%. The more common signs
      were pallor 97%, hepatomegaly 82%, fever 79,1%, malnutrition 75,2%, systolic
      heart murmur 77,9%, jaundice 71,6%, lymph node enlargement 70,1%.Signs observed
      during the hospital course were 29,4% lower extremities edema, 22,6% myalgia,
      16,4% pericardial effusion, 16,4% generalized edema. The more common
      gastrointestinal signs were hepatomegaly 82%(52/68), jaundice 71,6% (48/68) and
      splenomegaly 29,4%(20/68).The -lower liver border was found between 1 to 4 below
      the lower rib border in 71,6%(48/67) and below 5 cm b. l. r. b. in
      11,9%(8/67).60% had abnormal liver function tests, 54,6% had mainly direct
      bilirrubin elevationand 45,4% mainly indirect.SGOT was elevated in 28,5% and SGPT
      in 25%, 28,3% had elevated alkaline phosphatase. The bilirrubin media was 3,5
      mg/dI (range 0,6-21), the indirect bilirrubin media was 1,6 mg/dI (range 0,5
      11,5), the direct bilirrubin media was 1,9 mg/dI (range 0,3-18), The SGOT media
      73,9 U/L (range 9-1250), SGPT media 65,5U/L (range 6-1596). Alkaline phosphatase
      5,9 mui/ml (range 3-497). Albumin media 3,09 (range 2-4,2).Patients with
      bacterial coinfection (salmonella, staphilococcus, enterobacter, shigella) had a
      higher increase in bilirrubin and transaminases.Three patients had liver
      biopsies, two revealed Kupffer cells hyperplasia (moderate to severe), one
      revealed intracellular hyperplasia, one patient coinfected with diseminated
      hystoplasmosis had granulomas in the liver.Mortality(8,8%) was associated to
      hepatocellular involvement (SGOT media 330U/L, SGPT media 207 U/L, alkaline
      phosphatase media 183 mui/ml), hypoalbuminemia media = 2,4 gr/1) and generalized
      edema.

PMID- 12221436
TI  - [GASTRIC CANCER: DIAGNOSIS AND ROLE OFLYMPHADENECTOMY IN SURGICAL TREATMENT]
AB  - This prospective, non-controlled study assessed clinico pathologic features and 5
      year survival of 62 patients with gastric cancer seen at Belen Hospital, between
      1990 and 1994. Mean age was 59,3 years. There were 38 men and 24 women. Mean
      length of disease was 16 months. The most frequent symptoms were abdominal pain
      and pallor. The overall endoscopic and biopsy accuracy was 100% as compared to
      94% for endoscopy alone. We found improvement in endoscopy biopsy after obtaining
      more than 6 biopsies, in Borrmann's types I and II, located in the body or
      histologically diffuse. Most patients with inoperable and nonresectable disease
      were women (P = 0,006), had tumors greater than 10cm (p = 0,0001), stages III and
      IV (p = 0,0001) or diffuse tumors (p = 0,007) as compared with resectable cases.
      Most nodes were found in the perigastric region. The survival rate was different
      among patients with inoperable (n=10), non-resectable (n = 1 8), and resectable
      (n = 34) disease, with the 5-year survival rate being 0%, 0%, and 15%,
      respectively (p < 0,001). The survival rates of patients were significantly
      different among DO(n = 8), D1 (n = 9), and D2-D3(n = 17) dissections, with the 5
      year survival rate being 0%, 23%, and 41%, respectively (p < 0,0001). The 5 year
      survival rates for patients who underwent curative and palliative operation were
      60% and 7%, respectively (p < 0,0001). The 5-year survival rate for the total
      series was 10%. We concluded that only the patients that could be submitted to
      gastric resection had a survival perspective of more than 5 years, mainly those
      underwent extended lymphadenectomy.

PMID- 12221437
TI  - [LIVER CANCER IN HYPERENDEMIC AREA OF B AND DELTAHEPATITIS: REPORT OF 19 CASES]
AB  - This is a prospective study that includes 19 hospitalized patients with hepatic
      cancer at the Medicine Department of the Regional Hospital in Cuzco (Peru),
      between August 1992 to August 1995. Epidemiological and clinical information was
      obtained from all patients. Serum samples were taken for HBsAg, anti-Delta, and
      liver tests. Histological diagnosis was done in 14 patients by liver biopsy by
      the Menghini's method, in the others this was done by clinical and laboratorial
      means because the biopsy was contraindicated.92,9% were hepatocarcinoma, and this
      neoplasm was more frequently in men, between 20 to 39 years old. The risk factors
      were infections by hepatitis B virus and delta virus: 66.7% had HBsAg positive
      and 41,6% Anti-Delta positive. Excessive alcohol consumption was present in
      68,5%.We concluded that the most frequently cancer of the liver seen was
      hepatocarcinoma and the risk factors that are associated were previous infection
      of B and Delta virus and alcohol.

PMID- 12221438
TI  - [CHOLEDOCHAL CYST: ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY(ERCP) DIAGNOSIS
      VALUE]
AB  - We presented six cases of choledochal cysts all of whichwere diagnosed by ERCP.
      Patients were 12,13,17,20,29 and 36 years old. Five were female and one was a
      male. The main symptom was abdominal pain.The Endoscopic Retrograde
      Cholangiopancreatography showed the anatomic details of the biliary tree and the
      pancreaticobiliary ductal junction and also allowed us to decide the adecuate
      management of the patient.

PMID- 12221439
TI  - [NEW HEPATITIS VIRUSES]
AB  - Serum obtained from a surgeon (with the initials GB) with acute icteric
      hepatitis, permited the passages of two virus to tamarins; furthermore was
      possible to detect anti-bodies against the putative epitope of this viruses,
      designed GBV-A and GBV-B in several human populations; many years after that two
      different researchers teams identified a new virus GBV-C or HVG, based on very
      similar aminoacid sequence of both.The role of GB-viruses and hepatitis G virus
      in human pathology is not completely dear; but we can say some things as that the
      viruses can be categorized as belonging to the flavivirus family, are not related
      in any way with hepatitis C virus; GBV-A is a nonpathogen virus, GBV-B produce
      hepatitis in monkey but is not relevant in human, GBV-C and HGV are independent
      isolation of the same virus, and they can to produce liver injury, but seems to
      have a mild course.Finally GBV-WHGV accounts for only a minority of cases of
      hepatitis non A-E, and the majority of them are still waiting for identification
      of a new agent.

PMID- 12221440
TI  - [PREGNANCY AND LIVER CIRRHOSIS: REPORT OF A CASE]
AB  - Pregnancy in women with liver cirrhosis is unusual, because of the metabolic
      alterations that the liver disease produces.We report a case of a cirrhotic
      alcoholic patient who was pregnant twice. The first pregnancy was successful
      delivering a baby of 2,500g. On the second one, the patient died because of
      digestive hemorrahage caused esophageal varices the fetus also died.

PMID- 12221441
TI  - [BIG BRUNNEROMA AS UNUSUAL CAUSE OF INTESTINAL BLEEDING]
AB  - We reported a great Brunner's gland hamartoma (8x2,5x2 cm) which was present in a
      seventy-five year old woman with a 1 0-day history of melena.Gastroduodenoscopy
      showed an ovoid and movible tumor located within the duodenum. The endoscopic
      biopsy was negative because the tumor was totally in the submucosa. During
      surgery, a polypoid tumor was found in the second portion of the duodenum above
      the ampulla of Vater.The clinical, endoscopical, radiological, histological, and
      surgical features of Brunner's gland hamartoma, are reviewed.

PMID- 12221442
TI  - [HUMAN BALANTYDIASIS IN HUARAZ: REPORT OF FIVE CASES]
AB  - In order to know the clinical behavior of Human Balantidiasis, five symptomatic
      cases are reported (three from hospital and two from private practice), observed
      from December 1993 to December 1996 in the city of Huaraz (3,100 Mt above sea
      level). All patients were from Ancash, being their mean age 57,2 years old (3
      85); 4/5 were male, and 3/5 were farmers. They bred pigs, lived in a rural
      environment and had no access to drinking water nor to sewage at home. The mean
      length of this disease was 22,8 days (10-60). Clinical symptoms were dysenteric
      diarrhea and abdominal pain accompanied by fever, pallor, asthenia, weight loss
      and dehydration. All five cases presented the parasite in the feces: one as a
      cyst, two as trophozolte, and the other two, both shapes. Two patients suffered
      serious complications: The first one had intestinal perforation, peritonitis and
      died, and the other one presented bronchopneumonia, low digestive hemorrhage and
      sepsis. Treatment included tetracycline, metronidazole and large spectrum
      antibiotic, if required. When we observe a patient with hemorrhagic or chronic
      severe diarrhea in Huaraz, who comes from the rural area and is a breeder of
      pigs, we must consider a diagnosis based on Human Balantidiasis.

PMID- 12221443
TI  - [INTRAGASTRIC MIGRATION OF CLIPS. A NEW COMPLICATIONOF LAPAROSCOPIC VAGOTOMY]
AB  - Since 1989, when Kathdouda, M. D. and Mouiel, M. D. performed a laparoscopic
      vagotomy following the Taylor technique, there have been several reports of
      duodenal peptic ulcer laparoscopic treatment through different methods of
      vagotomy, from the trouncular to the supraselective or any of their varieties, as
      Taylor and Hill-Baker procedures. With the appearance of this new form of
      surgery, new complications are expected. This study reports the intragastrical
      migration of clips as a complication not yet reported. The possible
      etiopathogenic factors that could have influenced the appearance of such
      complication, are here discussed.

PMID- 12221444
TI  - Review article: MRI of the postoperative lumbar spine.
AB  - Imaging assessment of the lumbosacral spine following surgery is complex and
      depends upon several factors, including the anatomy of the patient, the surgical
      procedure and the disease process for which it was performed, the age of the
      patient, the biomechanical condition of the underlying cortical and cancellous
      bone, intervertebral disc and musculoligamentous tissues, the time since surgery
      procedure and the duration and nature of the postsurgical syndrome. Depending
      upon these factors, one or a combination of complementary imaging modalities may
      be required to demonstrate any clinically relevant abnormality, to assist the
      surgeon in deciding if repeat surgery is necessary, its nature and at which
      vertebral level(s) it should be directed. This review stresses the important role
      of MRI following lumbar discectomy, intervertebral fusion and/or instrumentation
      in achieving the most beneficial and timely outcome in the patient presenting
      with an acute, subacute or chronic failed back surgery syndrome.

PMID- 12221445
TI  - Pulse-wave encephalopathy: a comparative study of the hydrodynamics of
      leukoaraiosis and normal-pressure hydrocephalus.
AB  - There is a strong association between the occurrence of leukoaraiosis and normal
      pressure hydrocephalus (NPH). Venous compression secondary to alterations in
      craniospinal compliance is implicated in the pathogenesis of NPH, and venous
      pathology has also been implicated in leukoaraiosis. The purpose of this paper is
      to compare and contrast the blood-flow and fluid-pulsatility characteristics of
      these conditions. I initially studied 18 subjects without pathology, with MRI
      flow-quantification studies of the cerebral arteries and veins, to define the
      range of normality. The main study involved 10 patients with idiopathic dementia
      but no leukoaraiosis who served as controls, 50 with idiopathic dementia with
      varying degrees of leukoaraiosis and 18 with NPH. I compared blood-flow volumes,
      vascular pulse-wave amplitudes and velocities. There was no significant
      difference in blood flow across the dementia patients. In patients with moderate
      leukoaraiosis, arterial pulsatility was 69%, cerebrospinal fluid (CSF) pulsation
      104%, sagittal sinus pulsatility 48% and cortical vein pulsatility 34% higher
      than in demented patients without leukoaraiosis. Patients with NPH showed similar
      results with arterial pulsatility increased by 56% and sagittal sinus pulsatility
      by 70%. By contrast, the NPH patients' CSF pulse was 42% and the pulse wave delay
      at the sagittal sinus 50% less than in moderate leukoaraiosis. Thus,
      leukoaraiosis and NPH share increased arterial and sinus pulsatility. In
      leukoaraiosis cortical vein compliance is initially increased but in severe
      leukoaraiosis and NPH it is reduced.

PMID- 12221446
TI  - Intravascular malignant lymphomatosis.
AB  - Intravascular malignant lymphomatosis is a rare and probably often overlooked
      disease characterised by massive intravascular proliferation of lymphoid cells,
      usually with a poor prognosis. CT and MRI appearances are nonspecific; the most
      suggestive finding being both asymmetrical, bilateral, contrast enhancing high
      signal areas on T2 weighting and infarct-like lesions of the cortex and basal
      ganglia. We report two patients with previously unreported dural and spinal cord
      involvement.

PMID- 12221447
TI  - Magnetic resonance angiography with ultrashort echo times reduces the artefact of
      aneurysm clips.
AB  - We evaluated the ability of an ultrashort echo time (TE) three-dimensional (3D)
      time-of-flight (TOF) magnetic resonance angiography (MRA) sequence to reduce the
      metal artefact of intracranial aneurysm clips and to display adjacent cerebral
      arteries. In five patients (aged 8-72 years) treated with Elgiloy or Phynox
      aneurysm clips we prospectively performed a conventional (TE 6.0 ms) and a new
      ultrashort TE (TE 2.4 ms) 3D TOF MRA. We compared the diameter of the clip
      induced susceptibility artefact and the detectability of flow in adjacent
      vessels. The mean artefact diameter was 22.3+/-6.4 mm (range 14-38 mm) with the
      ultrashort TE and 27.7+/-6.4 mm (range 19-45 mm) with the conventional MRA (
      P<0.0001). This corresponded to a diameter reduction of 19.5+/-9.2%. More parts
      of adjacent vessels were detected, but with less intense flow signal. The
      aneurysm dome and neck remained within the area of signal loss and were therefore
      not displayed. Ultrashort TE MRA is a noninvasive and fast method for improving
      detection of vessels adjacent to clipped intracranial aneurysms, by reducing clip
      induced susceptibility artefact. The method cannot, however, be used to show
      remnants of the aneurysm neck or sac as a result of imperfect clipping.

PMID- 12221448
TI  - Primary cerebral non-Langerhans cell histiocytosis: MRI and differential
      diagnosis.
AB  - We report a young woman with primary cerebral non-Langerhans cell histiocytosis
      of the juvenile xanthogranuloma family. The clinical course was complicated by
      extensive infiltration of cranial nerves and meninges and epi- and intramedullary
      spinal dissemination. Whereas the cutaneous form of juvenile xanthogranuloma is
      usually benign and self-limited, central nervous system involvement is associated
      with high morbidity and mortality and might therefore be considered a separate
      clinical entity.

PMID- 12221449
TI  - Diffusion of water in large demyelinating lesions: a follow-up study.
AB  - We studied five patients with multiple sclerosis with one plaque of demyelination
      more than 2 cm in diameter, using conventional and diffusion-weighted MRI, soon
      after the onset of symptoms and over 1-36 months. The orientationally averaged
      diffusion coefficient <D> was increased in all the acute lesions, and increased
      further during follow-up in three. There was a strong correlation between <D> and
      the degree of low signal on T1-weighted images. The quantitative information
      provided by <D> allowed delineation of different diffusion patterns in large MS
      lesions, that may reflect heterogeneity of the anatomical substrate.

PMID- 12221450
TI  - Cerebellar peduncle myelinolysis: case report.
AB  - We present a case of bilateral middle cerebellar peduncle myelinolysis, in which
      the diagnosis modality was MRI.

PMID- 12221451
TI  - Hemorrhage in the cavum septi pellucidi, and a brief review of the literature.
AB  - The aim of this study is to present the cases of four neonates with hemorrhage
      within the cavum septi pellucidi (CSP). The sonographic findings of this rare
      location of intracranial hemorrhage, the related pathology and the possible
      underlying mechanisms are discussed, with a brief review of the literature. Three
      out of four of the neonates were premature and the fourth was a full-term infant
      with Down's syndrome. In all the patients the hemorrhage in the CSP was
      associated with severe intracranial hemorrhage.

PMID- 12221452
TI  - Progressive white-matter disease with primary cerebellar involvement: a separate
      entity?
AB  - Abstract. Although its metabolic basis has not yet been clarified, we report a
      progressive white-matter disease in a Turkish girl, starting in the cerebellum
      and spreading to supratentorial white matter. The onset was at the age of 2.5
      years with diabetes insipidus, followed by ataxia and pyramidal signs resulting
      in loss of walking. Aqueduct stenosis was first recognised at the age of 8 years.
      To our knowledge, this MRI and clinical pattern does not correspond to a
      recognised, well-defined white-matter disease and may indicate a separate entity.

PMID- 12221453
TI  - Lumbar nerve root avulsions with secondary ipsilateral hip dysplasia in a child.
AB  - We report on an 8-year-old child with avulsions of the left L3, L4 and L5 nerve
      roots and traumatic meningoceles that were not associated with lumbar spine or
      pelvic girdle fractures. The patient had a history of a road traffic accident.
      Plain radiographs of the pelvis revealed left hip dysplasia. The magnetic
      resonance imaging findings of the lumbar spine are illustrated. The pathogenesis
      of lumbar nerve root avulsions and their association with ipsilateral hip
      dysplasia are discussed.

PMID- 12221454
TI  - 3D visualisation of the middle ear and adjacent structures using reconstructed
      multi-slice CT datasets, correlating 3D images and virtual endoscopy to the 2D
      cross-sectional images.
AB  - The 3D imaging of the middle ear facilitates better understanding of the
      patient's anatomy. Cross-sectional slices, however, often allow a more accurate
      evaluation of anatomical structures, as some detail may be lost through post
      processing. In order to demonstrate the advantages of combining both approaches,
      we performed computed tomography (CT) imaging in two normal and 15 different
      pathological cases, and the 3D models were correlated to the cross-sectional CT
      slices. Reconstructed CT datasets were acquired by multi-slice CT. Post
      processing was performed using the in-house software "3D Slicer", applying
      thresholding and manual segmentation. 3D models of the individual anatomical
      structures were generated and displayed in different colours. The display of
      relevant anatomical and pathological structures was evaluated in the greyscale 2D
      slices, 3D images, and the 2D slices showing the segmented 2D anatomy in
      different colours for each structure. Correlating 2D slices to the 3D models and
      virtual endoscopy helps to combine the advantages of each method. As generating
      3D models can be extremely time-consuming, this approach can be a clinically
      applicable way of gaining a 3D understanding of the patient's anatomy by using
      models as a reference. Furthermore, it can help radiologists and
      otolaryngologists evaluating the 2D slices by adding the correct 3D information
      that would otherwise have to be mentally integrated. The method can be applied to
      radiological diagnosis, surgical planning, and especially, to teaching.

PMID- 12221455
TI  - Primary stenting as emergency therapy in acute basilar artery occlusion.
AB  - In three patients with acute occlusion of the basilar artery intra-arterial
      fibrinolysis resulted in only partial recanalization and revealed severe stenosis
      as the underlying cause. Application of micro-stents without previous dilatation
      resulted in vessel re-opening. Two patients had an excellent clinical outcome.
      One patient died 10 days after the stroke due to brainstem infarction. Emergency
      primary stent application may improve the outcome in acute basilar artery
      occlusion, if intra-arterial thrombolysis fails to re-establish a sufficient
      flow.

PMID- 12221456
TI  - Cyclosporin withdrawal with concomitant conversion from azathioprine to
      mycophenolate mofetil in renal transplant recipients with chronic allograft
      nephropathy: a 2-year follow-up.
AB  - Because recent large studies have demonstrated that mycophenolate mofetil (MMF)
      is superior to azathioprine (AZA) as a post-transplant immunosuppressant, it has
      been speculated that MMF could have a cyclosporin (CsA)-sparing effect in renal
      transplant recipients with chronic allograft dysfunction. Between April 1996 and
      October 1998, 31 patients with chronic allograft dysfunction were assigned to
      have conversion from AZA to MMF with concomitant CsA withdrawal. Patient and
      graft outcomes were analysed. Mean follow-up time after MMF conversion was 27+/
      11 months. Serum creatinine concentration (sCt) significantly decreased after
      conversion and remained stable at the end of follow-up (227+/-31 micro mol/l vs.
      185+/-50 micro mol/l; P<0.0005). Mean variation in sCt was -24% after conversion,
      whereas it was +20% in the year before conversion ( P<0.001). There was a
      significant inverse relationship between proteinuria at baseline and improvement
      in renal function (r=-0.35; P=0.01). Proteinuria increased during follow-up
      (0.79+/-0.6 vs. 1.79+/-1.08 g/day; P=0.04). Isolated CsA nephropathy was
      associated with the best outcome. Renal function significantly improved in
      patients with grade 1 chronic rejection and remained stable in patients with
      grade 2 chronic rejection. Two patients (6.5%) experienced late acute rejection,
      respectively 13 and 24 months after CsA withdrawal. Eight patients (29%)
      experienced systemic infections requiring hospitalization. Blood pressure control
      and lipid profile improved after conversion. CsA withdrawal with a concomitant
      switch from AZA to MMF allows a substantial and durable improvement in renal
      function. Both allograft histology and proteinuria at baseline are predictive of
      the evolution of renal function after conversion. Physicians should consider the
      risk of over-immunosuppression possibly associated with this therapeutic
      strategy.

PMID- 12221458
TI  - Kupffer cells play an important role in the cytokine production and activation of
      nuclear factors of liver grafts from non-heart-beating donors.
AB  - In the non-heart-beating donor (NHBD) deterioration of microcirculation of the
      liver graft is strongly associated with secretion of cytokines and eicosanoids.
      In this study we investigated the excretion of cytokines, eicosanoids, and DNA
      binding activity of transcription factors in the grafts from NHBD and evaluated
      the effects of the elimination of Kupffer cells on them. The purpose of this
      study was to clarify the impact of Kupffer cells on transcription factor activity
      and the that of cytokine and eicosanoid production on reperfusion injury of liver
      grafts from NHBD. Wistar rats were allocated to four groups: (a). control group:
      livers were extracted under heart-beating conditions and perfused without cold
      storage, (b). heart beating (HB) group: livers extracted under heart-beating
      conditions were perfused after 6 h of cold storage, (c). non-heart-beating (NHB)
      group: livers extracted after cardiac arrest were perfused after cold storage,
      (d). Kupffer cell eliminated (KE) group: liposome-encapsulated dichloromethylene
      diphosphonate was intravenously administered to eliminate Kupffer cells before
      extraction, and the liver was perfused after cold storage. Cytokines and
      eicosanoids in perfusate were measured. DNA binding activity of nuclear factor
      kappa B, activating protein 1, and nuclear factor-interleukin 6 of tissue were
      investigated. Concentrations of interleukin 1 beta and thromboxane B(2) in the
      perfusate were significantly higher in NHB group, but they were completely
      suppressed in the KE group. A rise in binding activity of nuclear factor kappa B
      and activating protein 1 was not observed during cold storage in any groups, but
      these activities did increase remarkably after reperfusion. Significant buildup
      of those activities were recognized in the NHB group, and this phenomenon was
      inhibited in the KE group. The histological structures of the sinusoid in the KE
      group were well maintained, as with those of the control group. These results
      indicate that cytokines, eicosanoids, and the DNA binding activity of the
      transcripton factor are strongly associated with reperfusion injury, and Kupffer
      cells play an important role in this mechanism in grafts from NHBDs.

PMID- 12221457
TI  - Lymphocyte subsets and assessment of cancer risk in renal transplant recipients.
AB  - Renal transplant recipients have a well-recognized increased risk of de novo
      neoplasia. In this study, we investigated whether lymphocyte subset count could
      predict the risk of developing noncutaneous neoplasia (NCSC) in renal transplant
      recipients (RTR). Between January 1995 and December 1995, lymphocyte subsets
      (CD4, CD8, CD19) were measured in 281 RTR. This population was studied until
      November 1999 for the development of NCSC. The mean follow-up was 42+/-9 months.
      Neoplasm was diagnosed in 22 patients (7.9%). Patients who developed a cancer
      were significantly older (53.8+/-6 years vs 38+/-16 years, P<0.0001), had lower
      CD4 (234+/-126/mm(3) vs 543+/-214/mm(3), P<0.005) and CD19 (19+/-9/mm(3) vs 51+/
      22/mm(3), P<0.0001) levels, and more frequently had past histories of skin cancer
      (24% vs 4%, P<0.01). Cox regression revealed that high CD4 levels (RR 0.73, 95%
      CI 0.62-0.89 for each 100/mm(3) increase in CD4 cell count) were associated with
      decreased risk of NCSC, whereas age (RR 2.49, 95% CI 1.12-5.92 for each 10-year
      increase in age) was predictive of the subsequent development of NCSC. To
      conclude, CD4 cell depletion is associated with the development of solid cancers
      and lymphoma in RTR.

PMID- 12221459
TI  - Improvement of post-transplant lymphocele treatment in the laparoscopic era.
AB  - Post-transplant lymphoceles are a common problem after renal transplantation,
      often inflicting the graft or adjacent iliac veins. Since 1991, there have been
      many reports on laparoscopic fenestration as the treatment of choice, but no
      larger series has been presented. At our department, 63 laparoscopic procedures
      were performed between 1993 and 2001 among 1502 renal graft recipients. The
      laparoscopic operation time, conversion rate, hospital stay, and complications
      have all decreased progessively. Duration of hospital stay and convalescence was
      markedly longer in patients treated with conventional open surgery (27 patients).
      Rejections, CMV disease, and post-transplant reoperations seem to have an
      increased incidence in the lymphocele population. According to our experience,
      laparoscopic fenestration is the superior treatment for symptomatic lymphoceles,
      allowing minimal trauma and fast recovery. Our series suggests that the rate of
      complications/graft injury decreases progressively with experience. Laparoscopic
      ultrasound seems useful in difficult cases. Prophylactic measures should be
      emphasised at the time of transplantation and reoperations.

PMID- 12221460
TI  - Modified extravesical ureteral reimplantation and routine stenting in kidney
      transplantation.
AB  - In the past, extravesical ureteroneocystostomy has been technically modified
      several times, with varying results. In this study, we evaluate our experience
      with modified extravesical re-implantation and routine stenting. From January
      1988 to September 2001, 411 consecutive renal transplantations (220 LRD/LUD, 191
      CAD) were performed at our institutions. Of 220 kidneys utilized for living
      related transplantation, 39 were retrieved laparoscopically and 181 were
      retrieved by open nephrectomy. The ureteroneocystostomy performed was a modified
      Lich-Gregoir re-implantation with routine stenting, using the upper transplant
      ureter. A double ureter was encountered in 11 patients and was managed with a
      conjoint ureteral ostium-to-mucosa anastomosis, using two stents. In two patients
      with graft ureteropelvic junction (UPJ) stenosis, a double ipsilateral drainage
      was performed, applying modified extravesical reimplantation with concomitant
      ureteroneocystostomy. There were no ureteral leaks. Five (1.22%) patients
      developed temporary ureterovesical junction (UVJ) obstruction/edema following
      stent removal, which necessitated re-stenting for 4-6 weeks. Two patients (0.49%)
      developed delayed stenosis and were successfully treated with retrograde balloon
      dilatation.(One at the UPJ of a pediatric kidney, and one at UVJ). All patients
      with functioning grafts in this series are currently stent-free. We conclude that
      the modified extravesical reimplantation with routine stenting is an effective
      and safe technique in renal transplantation, associated with almost no
      complications.

PMID- 12221461
TI  - Significance of monocytic cytokines at single cell level for the immune
      responsiveness in renal transplant recipients.
AB  - Cytokine dysregulation is an important factor underlying the immune
      unresponsiveness to hepatitis B vaccination (HBV) in renal transplant recipients.
      This study investigated the relationship between monocyte-derived interleukin-6
      (IL-6) and interleukin-10 (IL-10) production and the immune responsiveness using
      flow cytometry (cytoflow) after whole blood culture. According to their previous
      response to hepatitis B vaccination, 40 renal transplant recipients were divided
      into two groups of 20 patients. The percentage of CD 14+ monocytes stained
      positive for intracellular IL-6 or IL-10 was measured using flow cytometry after
      4 and 20 h of whole blood culture with lipopolysaccharide stimulation. The
      percentage of CD 14+/IL-6+ cells after incubation in vitro for 4 h was lower in
      the responders compared to the non-responders and controls (27.15+/-8.93 vs
      35.47+/-9.95, P=NS; and 37.06+/-10.89, P<0.05 respectively). The staining
      intensity of IL-6 at 4 h for responders was also significantly reduced. At 20 h,
      there were a significantly higher percentage of CD 14+/IL-10+ positive cells in
      the responders compared to the non-responders (41.87+/-18.39 vs 27.55+/-17.25,
      P<0.05). These results indicate that alteration of intracellular cytokine profile
      in activated monocytes distinguishes the HBV vaccination responders from the non
      responders among renal transplant recipients. The capacity to upregulate monocyte
      IL-10 production in this subset of patients may modulate the immune
      responsiveness and effectively assists in mounting a positive response to HBV
      vaccination.

PMID- 12221462
TI  - The evaluation of graft irradiation as a method of preventing hemolysis after ABO
      mismatched renal transplantation.
AB  - Hemolysis may occur after organ transplantation. In most cases, hemolysis is drug
      related, such as to cyclosporin, etc. However, it is important to consider graft
      versus-host antibody formation as one of the causes of hemolysis. We evaluated
      the effect of local graft irradiation as a method of preventing hemolysis arising
      from ABO antibody formation after ABO-mismatched renal transplantations. The
      participants in this study were 44 patients who had undergone ABO-mismatched
      renal transplantation. Of these patients, 23 were subjected to postoperative
      local irradiation, and 21 were not. We examined the characteristics of anti-blood
      type antibodies, and we also compared the frequency of the development of
      antibody formation and hemolysis development between the groups. The development
      rates of anti-ABO-antibody formation and hemolysis were significantly higher in
      the patients without local irradiation (15/21, 71%; 6/21, 29%) than in those with
      local irradiation (1/23, 4%; 0/23, 0%). The elevated antibodies mainly belonged
      to the IgG class, not the IgM class. The hemolysis- and antibody formation
      observed in the patients originally without postoperative local irradiation was
      dramatically improved by graft irradiation. Local graft irradiation after ABO
      mismatched renal transplantations may be needed to prevent the formation of anti
      ABO antibodies and to impede the development of hemolysis.

PMID- 12221464
TI  - Which ABO-matching rule should be the decisive factor in the choice between a
      highly urgent and an elective patient?
AB  - ABO blood group matching policy between donor and recipient is a key element of
      organ allocation. Unequal distribution of the ABO blood groups in the population
      can lead to inequities in the distribution of organs to potential recipients.
      Furthermore, High Urgency liver transplant candidates might compromise the
      chances of transplantation for the elective patients. To compare the influence of
      the various ABO blood group matching policies on the transplantation rate of HU
      patients and on the subsequent donor liver availability for elective patients, a
      simulation study was undertaken. The study shows that in the Eurotransplant liver
      allocation program, a restricted ABO-compatible matching policy for HU liver
      patients offers the highest probability of acquiring a liver transplant, for both
      High Urgency- and elective patients, irrespective of their ABO blood group. A
      simulation study once again proved to be an elegant tool for objectively
      analysing various options in a complex organ allocation algorithm.

PMID- 12221463
TI  - Ultrastructural analyses of pancreatic grafts preserved by the two-layer cold
      storage method and by simple cold storage in University of Wisconsin solution.
AB  - The two-layer cold storage method (TLM) using University of Wisconsin (UW)
      solution supplies sufficient oxygen to pancreatic grafts during preservation and
      extends pancreas preservation time to up to 96 h in the canine model. Simple cold
      storage in UW (UWM) on the other hand, preserves canine pancreas grafts for up to
      72 h by preventing cell swelling, mainly because of its high osmotic pressure.
      The aim of this study is to analyze morphologically dog pancreatic grafts
      preserved by these two methods with their different mechanisms. Immediately after
      preservation of canine pancreata by TLM for 72 h and 96 h (group 1 and group 3,
      respectively), and by UWM for 72 h and 96 h (group 2 and group 4, respectively),
      tissue ATP levels were determined using high-performance liquid chromatography
      (HPLC), and detailed morphological analyses of intragraft components were
      performed using light- and electron microscopy. The mean areas of one
      mitochondrion and rough endoplasmic reticulum (RER) vacuolization were calculated
      by computer-graphic analyses using NIH image 1.62 f soft. The tissue ATP levels
      were significantly higher in groups 1 and 3 than groups 2 and 4 ( P < 0.05).
      Light microscopy demonstrated no marked difference among the 4 groups. By
      electron microscopy however, mitochondrial swelling and RER vacuolization were
      observed in acinar cells to various extents in the 4 groups. They were
      significantly more evident in group 2 than group 1 ( P < 0.05), and in group 4
      than group 3 ( P < 0.05). In conclusion, TLM demonstrated excellent protection of
      intracellular organelles, mitochondria, and RER, up to 72-96 h. Well-maintained
      graft ATP levels in TLM groups may result in maintaining the integrity of
      intracellular organelle membranes as well as cellular membranes.

PMID- 12221465
TI  - [Keloids. A fibroproliferative disorder of unknown etiology].
AB  - We review recent advances in keloid research and treatment. Keloids are benign
      tumours of the skin. They tend to occur in younger patients after different kinds
      of injuries, infections or they may develop spontaneously. In contrast to
      hypertrophic scars, keloids are not confined to the original wound, but grow into
      the corresponding healthy skin. They rarely recede within time. Most patients
      complain of itching and suffer from impairment of their quality of life. Only
      little is known about the pathogenesis of keloids, although they have been
      clinically well characterized for a long time. New results point towards a
      disruption in the signaling pathway of TGFbeta. In addition there seems to be
      evidence of an increased familiar incidence and therefore the genetic background
      should be screened. Successful treatment of keloids is difficult. As contact
      cryotherapy and intralesional corticosteroid injections are in most cases not
      successful, the pulsed dye-laser seems to be a promising alternative. In addition
      topical treatment with extracts of onions, occlusive silicone sheets and pressure
      improves the clinical appearance of keloids.

PMID- 12221466
TI  - [Skin diseases in organ transplant patients].
AB  - In Germany 3273 visceral organs were transplanted in the year 2000. Together with
      patients grafted abroad, it is estimated that between 70,000 and 100,000 organ
      transplant patients are currently living in Germany. With the provision of
      lifelong immunosuppression the survival-time of these patients can exceed more
      than 20 years. In the first year following transplantation special emphasis is
      given to the prevention of viral, bacterial and fungal infections. Regular
      dermatological screening can provide early diagnosis of even systemic infections.
      An increased incidence of skin cancer parallels the extended survival rates of
      grafted patients. Within the first 5 years of immunosuppression 40% of these
      patients develop pre-malignant skin tumors such as actinic keratoses, dysplastic
      nevi, squamous cell carcinomas and basal cell carcinomas. Squamous cell
      carcinomas show an aggressive biology and an uncommon clinical morphology. The
      increased incidence of cancer is now responsible for a mortality rate of 5-8% in
      grafted patients. Against a background of lifelong immunosuppression, other risk
      factors include sun exposure and infections with oncogenic viruses. The rapidly
      growing numbers of allograft recipients as well as the rising long term survival
      rates of these patients demand the provision of high quality interdisciplinary
      and dermatological care in this field.

PMID- 12221467
TI  - [Guidelines for varicocele management].

PMID- 12221468
TI  - [Long-term results of adjuvant chemotherapy after therapeutic lymph node
      dissection in patients with cutaneous malignant melanoma].
AB  - BACKGROUND AND OBJECTIVE: 224 patients with malignant melanoma and palpable
      axillary or inguinal lymphadenopathy underwent therapeutic lymph node dissection
      at the Martin-Luther-University in Halle, Germany. between 1983 and 1994. 120
      received adjuvant chemotherapy; we evaluated the effects of various regimens in
      this group. PATIENTS/METHODS: Surgical treatment alone was performed in 104
      patients. This group's results were compared to those of 94 patients who
      additionally received an adjuvant polychemotherapy [dacarbazine (DTIC),
      vincristine, 5-fluorouracil and hydroxyurea] and 26 patients who received either
      DTIC monotherapy or DTIC plus interferon-alfa. RESULTS: The median follow-up was
      88 months. The 5-year survival rates were 31.0+/-5% after surgery alone, 26.4+/
      4% after adjuvant polychemotherapy and 27.0+/-9% after DTIC based chemotherapy.
      The three survival curves did not differ significantly. In a multifactorial
      analysis, the number of metastatic lymph nodes was the single significant
      predictor of survival after therapeutic lymph node dissection, whereas Breslow
      thickness, ulceration, site of the primary melanoma, age, sex and adjuvant
      therapy were not significant. CONCLUSION: No beneficial effect of adjuvant
      chemotherapies could be demonstrated.

PMID- 12221469
TI  - [Multiple superficial basal cell carcinomas following chronic ingestion of sodium
      hydrogen carbonate containing arsenic].
AB  - Basal cell carcinomas (BCC) are caused by various factors such as ultraviolet
      light, ionizing radiation, possibly human papilloma viruses and chemical agents.
      Among the latter inorganic trivalent arsenic has long been recognized as an
      important cause of BCC. A 70-year-old woman developed multiple basal cell
      carcinomas mainly on the trunk after taking sodium hydrogen carbonate
      contaminated with arsenic for many years for chronic gastritis.

PMID- 12221470
TI  - [Congenital bullous poikiloderma (Kindler syndrome)].
AB  - We report on an 18 years old female patient who presented with synechia of the
      labia. History reveals congenital blistering with acral localization and
      photosensitivity in childhood. At present, the patient showed wide-spread
      poikoloderma with reticulate hyperpigmentation, xerosis, proximal synechia
      between fingers and toes and absence of dermatoglyphics, suggestive for
      congenital bullous poikiloderma (Kindler syndrome). The diagnosis was confirmed
      by histology and electron microscopy. Kindler syndrome is a rare, autosomal
      recessive disorder with synechia of mucosal areas being the presenting symptom.

PMID- 12221471
TI  - [Keratosis lichenoides chronica. Bath PUVA therapy].
AB  - We describe the case of a 51-year-old male patient with characteristic lesions of
      keratosis lichenoides chronica confined to the back of his hands and feet. The
      lichenoid papules, linear hyperkeratotic ridges and erythematosquamous plaques
      appeared first in early childhood and recurred after a short episode of
      spontaneous remission. They didn't respond to various topical treatment
      modalities over the years. After a local PUVA therapy all lesions disappeared
      with no recurrence for over two years now. Our case report indicates a new
      promising indication for bath-PUVA-therapy.

PMID- 12221472
TI  - [Persistent inflammatory reaction at the injection site of Il-2 with lymphoma
      like inflammatory infiltrates].
AB  - Interleukin-2 (Il-2) is widely used for treatment of carcinomas, leukemia, and
      melanoma. Adverse drug effects of Il-2 include various systemic and generalized
      cutaneous drug reactions. In the following we report on a persistent inflammatory
      reaction at the injection site of Il-2. A patient received chemoimmuno-therapy
      for treatment of metastasizing melanoma, including subcutaneous application of
      recombinant interleukin-2 (Proleukin((R))). Within a few days reddish nodules
      developed at the injection sites that persisted after cessation of Il-2
      injections for two years until final lethal outcome. Histologic examination
      revealed a lobular panniculitis expressing atypical lymphocytes and
      multinucleated histiocytes.

PMID- 12221473
TI  - [Mechanisms of epithelial regeneration].

PMID- 12221474
TI  - [Removal of ticks with scalpel or disposable razor].

PMID- 12221475
TI  - National Academy of Neuropsychology/Division 40 of the American Psychological
      Association practice survey of clinical neuropsychology in the United States,
      Part I: practitioner and practice characteristics, professional activities, and
      time requirements.
AB  - Leaders of the National Academy of Neuropsychology and Division 40 (Clinical
      Neuropsychology) of the American Psychological Association determined that
      current information on the professional practice of clinical neuropsychology
      within the United States (U.S.) was needed. These two organizations co-sponsored
      a national survey of U.S. clinical neuropsychologists that was conducted in
      September 2000. The primary goal of the survey was to gather information on such
      topics as: practitioner and practice characteristics, economic variables (e.g.,
      experience with major third party payors, such as Medicare and managed care),
      practice expenses, billing methods, experiences with Current Procedural
      Terminology (CPT) codes, time spent on various clinical tasks, use of assistants,
      and income. The adjusted return rate of 33.5% (n = 1,406) reflects the number of
      surveys returned with sufficient data by licensed doctoral level clinicians with
      membership in one or both sponsoring organizations. In this first of two articles
      describing the survey results, characteristics of practitioners and practices,
      various types of professional activities, and time requirements for clinical
      tasks are presented and discussed. It was noted that the proportion of women in
      the field is increasing rapidly. Private practice is the predominant employment
      setting. Findings also document that members of the two sponsoring organizations
      are very similar with regard to employment setting, professional characteristics,
      and weekly activities. That is, involvement in clinical practice and research, as
      well as private practice versus institutional employment, was very similar
      between organizations. However, across organizations, work setting (private
      practice vs. institution) was associated with significant and meaningful
      differences. Private practitioners have a more diverse set of weekly clinical
      activities, are less likely to use assistants, and engage in more forensic
      activities. Across work setting, with the exception of forensic evaluations,
      those using assistants invest a greater number of hours per evaluation, but bill
      approximately the same numbers of hours per evaluation.

PMID- 12221476
TI  - Screening for dementia in "real world" settings: the cognitive assessment
      screening test: CAST.
AB  - Among elderly people who do not present with complaints of memory impairment,
      dementia is often missed by physicians, and time-consuming screening tests
      requiring expertise to administer and interpret are rarely done. Easily
      administered, reliable and cost effective dementia screening tests are needed for
      elderly individuals. The "pencil and paper" Cognitive Assessment Screening Test
      (CAST) takes minimal examiner time/training, and is both sensitive and specific
      in discriminating demented patients from healthy controls. The objectives of this
      study were to: (1) confirm the validity of the CAST in identifying individuals
      with dementia in a real-world setting (nonassisted living retirement community);
      (2) compare the sensitivity and specificity with other screening tests and
      extensive psychometric tests; and (3) assess the reliability of the CAST in test
      retest conditions over time. The CAST was both sensitive and specific and showed
      reliability on retesting. The CAST is both simpler to administer and more
      accurate than other screening tests for elderly subjects.

PMID- 12221477
TI  - A short version of the Hooper Visual Organization Test: development and
      validation.
AB  - Based on a previous analysis of the test protocols of 320 German-speaking
      neurological patients (Merten & Beal, 1999), a short form of the Hooper Visual
      Organization Test (VOT) was developed and examined using an independent sample
      composed of another 320 patients with a mean age of 55.7 years. Of the original
      30 VOT items, 15 were maintained. Estimates of internal consistency for the
      resulting short form yielded acceptable results (0.82 and 0.84). Particularly
      high correlations of the short form (0.71) and the original VOT (0.75) were found
      with WAIS Block Design. Scoring rules for the proposed short version were
      thoroughly revised, and expanded test instructions presented, which includes a
      graphic demonstration of the task. Based on a regression analysis with the total
      sample of N = 640, preliminary cutoff points for the short version can be
      computed from traditionally employed VOT cutoffs.

PMID- 12221478
TI  - Cumulative illness and neuropsychological decline in hospitalized geriatric
      patients.
AB  - A substantial portion of elderly patients admitted for inpatient rehabilitation
      treatment evidence cognitive dysfunction. Frequently, such patients also present
      with considerable medical comorbidity, that is, multiple concurrent illnesses.
      Identifying the potential role of cumulative illness in the etiology of cognitive
      decline in this group of frail elderly is limited by a lack of empirical
      information as little is known about this relationship. The goal of the present
      research was thus to investigate the relationship between cumulative illness and
      cognitive dysfunction while controlling for age and neurological and psychiatric
      symptomatology as these are previously known to affect cognitive function.
      Results indicate that cumulative illness predicts neuropsychological decline
      beyond the effects attributable to advanced age, mood, neurological pathology and
      psychiatric impairments. Even mild illness, if cumulative across several physical
      systems, can be predictive of cognitive deficits in this frail population. Of 11
      organ systems studied, impairment of the vascular system was associated with the
      most diffuse profile of declined neuropsychological performance. Performances on
      measures of reasoning and judgment showed the strongest associations with
      cumulative illness. Implications of findings for neuropsychological diagnosis and
      prognosis are reviewed.

PMID- 12221479
TI  - Neuropsychological assessment and employment outcome after traumatic brain
      injury: a review.
AB  - While there may be many reasons for obtaining neuropsychological assessment after
      traumatic brain injury (TBI), prediction of real world functioning is generally a
      key goal. The present paper reviews 23 studies concerning the relationship
      between neuropsychological test results and employment outcome after TBI. The
      review was conducted in accordance with guidelines developed by the Committee on
      Empirically Supported Practice of Division 40 (Neuropsychology) of the American
      Psychological Association. Results of the review support a Category A (strongly
      supported) recommendation for the use of early neuropsychological assessment to
      predict late employment outcome. Studies of late neuropsychological assessment
      and subsequent employment outcome and studies of concurrent neuropsychological
      assessment and employment outcome were inconclusive regarding either support or
      contraindication for neuropsychological assessment to predict employment outcome.
      Almost all studies conducted at these late or concurrent time points had
      significant limitations with regard to study type or adequacy of methodology.
      However, there is no conceptual basis for believing that neuropsychological
      findings obtained closer in time to assessment of employment outcome should be
      less predictive of this outcome than neuropsychological findings obtained at an
      earlier time.

PMID- 12221480
TI  - Detecting malingered performance with the Wisconsin card sorting test: a
      preliminary investigation in traumatic brain injury.
AB  - The present study examined the classification accuracy of four potential
      Wisconsin Card Sorting Test malingering indicators (Bernard and Suhr formulas and
      two types of Unique responses). Participants were 89 traumatic brain-injury (TBI)
      patients assigned to malingering and nonmalingering groups on the basis of the
      Slick, Sherman, and Iversion (1999) criteria. Individual Sensitivities were
      greater than .33 with acceptable Specificity. Combined Sensitivity for two of the
      indicators was greater than.60. Overall, this study demonstrated three distinct
      approaches to the WCST used by probable malingerers. The clinical relevance of
      these findings and directions for future research are discussed.

PMID- 12221481
TI  - Proceedings of the 8th Annual Meeting of the Bielschowsky Gesellschaft,
      Regensburg, Germany, July 6th to 8th 2001.

PMID- 12221482
TI  - Effect of inferior oblique recession in strabismus sursoadductorius.
AB  - The aim of this retrospective study was a quantitative analysis of the effect of
      graded inferior oblique recessions (8 mm, 10 mm or maximal) in strabismus
      sursoadductorius. METHOD: 234 patients (2-81 years of age) with unilateral
      strabismus sursoadductorius and stereopsis were operated between 1990 and 1999.
      Maximal recession (14.6 mm) included an anteroposition to the lateral aspect of
      the insertion of the inferior rectus. Before and three months after the
      operation, horizontal and vertical deviations (VD) were assessed by cover testing
      in five positions of gaze. In 121 patients, additional subjective quantitative
      assessment, including cyclodeviation measurement, was carried out with Harms'
      tangent screen. RESULTS: The mean effect of the operation on VD in 25 degrees
      adduction increased from 6 degrees with 8 mm recession to 10 degrees with maximal
      recession. It was related more to the amount of preoperative VD in adduction than
      to the amount of recession. One patient had a limitation of elevation with a
      hypotropia of >4 degrees, 7% needed further surgery because of undercorrection.
      DISCUSSION: Maximal recession of the inferior oblique muscle is a suitable
      procedure even in patients with marked strabismus sursoadductorius. The rate of
      functional undercorrection is low and there is no risk from general anesthesia or
      significant postoperative limitation of elevation.

PMID- 12221483
TI  - Kestenbaum and artificial divergence surgery for abnormal head turn secondary to
      nystagmus. Specific and nonspecific effects of artificial divergence.
AB  - Recommendations concerning the kind and dosage of eye muscle surgery for
      nystagmus vary in the literature. The present paper is an evaluation of the
      effects of Kestenbaum and artificial divergence surgery on abnormal head posture
      in a retrospective study. Exclusively patients with surgery for nystagmus-related
      horizontal head-turn (HT), with binocular vision and without previous eye muscle
      surgery were considered. Of the 78 patients, aged 3 to 68 years, 52 had a HT to
      the left side; 47 patients were male. In the Kestenbaum group (n = 31), the
      preoperative HT of 30 degrees (20-40) (median, 0.1-0.9 quantile) was reduced to
      10 degrees (0-30) by surgery of 14 mm (10-20) on each eye. Four patients received
      further surgery. In the artificial divergence group (n = 27), the HT of 30
      degrees (25-40) was reduced to 5 degrees (0-20) by recess-resect surgery of 10 mm
      (7-12) on the adducted eye. Seven patients needed further surgery. In the
      combined Kestenbaum plus artificial divergence group (n = 20), the HT of 30
      degrees (25-40) was reduced to 7 degrees (-5-15) by surgery of 29 mm (21-37) on
      both eyes together. No further surgery was necessary. Kestenbaum surgery had a
      similar effect/dose ratio as recess-resect surgery for strabismus. If a test with
      base-out prisms suggests that artificial divergence is promising, this concept is
      preferable. It can be integrated into Kestenbaum surgery.

PMID- 12221484
TI  - Smooth pursuit eye movements in patients with ocular motor nerve palsies: a
      preliminary report.
AB  - The trajectories, velocity, and co-ordination of smooth pursuit eye movements
      were investigated in 30 patients with ocular motor nerve palsies (including
      palsies of cranial nerves III, IV and VI). The recordings of horizontal and
      vertical eye movements were obtained by video-oculography under monocular viewing
      conditions. During the recordings, horizontal, vertical, and oblique target
      movements of 10 degrees /s constant velocity were presented to the subjects in
      succession. In contrast to normal subjects, smooth pursuit eye movements in
      patients with ocular nerve palsies showed considerable differences in dependence
      on the fixating eye. The smooth pursuit gain of the paretic eye was reduced for
      eye movements in the pulling plane of the paretic muscle. When viewing with the
      paretic eye, the tracking of the target was achieved by a series of refixation
      saccades, which also occurred in the occluded normal eye. Consequently, the sound
      eye position overshot the target. The transition from a smooth to a saccadic
      pursuit pattern was accompanied by a spatial deviation of the eye movement
      trajectories from the path of the fixation target.

PMID- 12221485
TI  - A preliminary report about the relation between visual acuity increase and
      compliance in patching therapy for amblyopia.
AB  - PURPOSE: The aim of this study was to establish a relation between visual acuity
      increase and compliance in children who have been prescribed patching therapy for
      their amblyopic eye. METHODS AND MATERIALS: In 14 new amblyopic children (mean
      age 4.3 +/- 1.9 years) compliance was measured electronically during one week,
      six months after starting patching therapy, with an Occlusion Dose Monitor (ODM),
      distributed through house visits. The children were diagnosed with anisometropia
      (5), strabismus (4) and anisometropia and strabismus (5). The degree of amblyopia
      was expressed as the ratio between the acuity of the amblyopic eye and the acuity
      of the good eye. Satisfactory increase in acuity was assessed by means of the
      following three criteria: acuity amblyopic eye / acuity good eye >75%, acuity
      exceeding 0.5 E-chart, three lines LogMAR acuity increase. RESULTS: Fourteen
      reliable recordings were obtained, which showed that children who did not patch,
      or were patched inconsistently, did not reach satisfactory acuity increase.
      CONCLUSION: There is indeed a statistically significant relation between acuity
      increase and measured compliance.

PMID- 12221486
TI  - The history of research into the disorders of reading and accommodation in
      strabismic amblyopia.
AB  - During the past 150 years, research on amblyopia and nystagmus has developed in
      five different waves (W1-W5). Amblyopia was initially regarded to be enigmatic
      and believed to be related to eccentric fixation (W1, after 1850); later, it was
      ascribed to disorders in refraction or accommodation (W2, around 1900). After
      1900 (W3), phylogenetic explanations appeared, and after 1945 (W4) concepts based
      on successful orthoptic practice came to the fore. Since 1965 (W5), research on
      amblyopia has been guided by modern insights into neuroanatomy and
      neurophysiology. In contrast to amblyopia, nystagmus has always been a well
      defined symptomatic entity. Even though amblyopia and nystagmus are both symptoms
      of strabismus, their understanding has therefore developed along different paths.
      In juvenile strabismus, defects in binocularity lead to monolateral amblyopia,
      while defects in contour vision lead to bilateral nystagmus. In the present
      paper, these five waves of amblyopia research are described in more detail, with
      particular attention to the concepts of adaptation, visual fields, and sensory
      and motor functions as related to disorders in reading and accommodation.

PMID- 12221487
TI  - Neuroanatomical and neurophysiological consequences of strabismus: changes in the
      structural and functional organization of the primary visual cortex in cats with
      alternating fixation and strabismic amblyopia.
AB  - In recent years, evidence has accumulated indicating that long-ranging neuronal
      connections within the primary visual cortex (area 17) mediate the influences of
      context and experience, possibly also those of expectation. After early onset
      strabismus, the layout of these connections is massively modified: in strabismic
      but not in normally raised cats, horizontal connections extend primarily between
      neurons activated by the same eye. As a possible consequence of the modified
      circuitry, neuronal synchronization between different ocular dominance domains is
      also massively reduced. Thus, the inability of strabismics to combine the signals
      arriving from the two eyes into a single percept may be caused by these
      structural and functional changes. Strabismic amblyopia is also accompanied by
      significant modifications of intracortical associational interactions:
      corresponding to the psychophysical deficits, neurons driven by the normal eye
      displayed stronger synchronization of their responses than neurons dominated by
      the amblyopic eye.(1) These data demonstrated for the first time a clear
      neurophysiological correlate of strabismic amblyopia in area 17. They suggest
      that - similar to our observations in divergent squinters - at least some of the
      perceptual deficits of amblyopic patients are due to experience-dependent changes
      in intracortical circuitry. We analyze this question by combining optical imaging
      of intrinsic signals with 3-D reconstructions of neuronal circuitry.

PMID- 12221488
TI  - Formation of a unilateral form deprivation myopia (FDM) due to a congenital
      eyelid entropium with a consecutive corneal ulcer: an illustrated case report.
AB  - Eye growth is regulated by a precise, sharp image of a distant object on the
      photoreceptor layer. A variety of laboratory investigations report that
      translucent occluders may induce axial eye elongation in animals. This axial
      growth is also called form deprivation myopia (FDM). In our pediatric
      ophthalmology clinic we observed the clinical correlate of FDM in a male infant
      with unilateral corneal ulcer due to a congenital tarsal malformation.
      Examination in the postnatal period under anesthesia revealed identical axial
      length in both eyes. Refraction of the affected eye could not be measured due to
      severe corneal ulcer. During an observation period of two years, the deep corneal
      opacification of the affected eye induced unilateral disproportionate axial
      elongation with formation of myopia. Formation of FDM may complicate treatment of
      amblyopia following unilateral media opacification. Periodic measurements of
      refraction should be performed to allow appropriate correction.

PMID- 12221489
TI  - Strabological results in patients with macular translocation surgery and
      counterrotation of the globe as a secondary procedure.
AB  - INTRODUCTION: Age-related macular degeneration is the most common cause of
      irreversible loss of visual acuity, including the ability to read, in elderly
      patients. One of the surgical treatment options is macular translocation with 360
      degrees retinotomy. The orthoptic results of torsional muscle surgery as a second
      procedure are demonstrated. MATERIALS AND METHODS: Between January 1999 and
      December 2000, the macula was rotated upward by 12-45 degrees in 10 eyes
      following complete artificial detachment and a 360 degrees retinotomy. In these
      patients, torsional surgery was carried out as a second procedure. Depending on
      the resulting cyclotorsion, we performed surgery on the oblique muscles only in
      four patients with a cyclotropia of 12-20 degrees and a combination of oblique
      muscle surgery with surgery of two or four rectus muscles in the remaining six
      eyes (cyclotropia over 21 degrees ). The pre- and postoperative diagnostic
      techniques included visual acuity, reading vision and the orthoptic status.
      RESULTS: Due to the unilateral ectopia of the macula, all patients presented
      postoperative strabismus with a vertical deviation of 2-10 degrees and a
      subjective cyclotropia between 12 degrees and 40 degrees. After surgery on the
      oblique muscles, the patients showed a residual cyclotropia of 0-6 degrees. In
      patients in whom surgery on the oblique muscles was accompanied by rectus muscle
      surgery, the remaining cyclotorsion was 5-13 degrees. Four patients excluded the
      non-operated fellow eye, six patients experienced double vision under binocular
      conditions and thus required prescription of additional prism glasses.
      CONCLUSION: Macular translocation causes diplopia under binocular conditions
      because of the unilateral ectopia of the macular region with cyclotropia and
      vertical deviation. These problems can be resolved or reduced by oblique muscle
      surgery or in combination with additional surgery on the rectus muscles,
      depending on the range of the cyclotorsion. Performing the torsional surgery as a
      second procedure after macular rotation with an exact preoperative measurement of
      the subjective cyclodeviation appears to be useful.

PMID- 12221490
TI  - Ocular neuromyotonia: a case report.
AB  - Ocular neuromyotonia is a rare motility disorder occurring after tumor
      irradiation near the skull base or as a consequence of vascular abnormalities.
      Ocular myasthenia, convergence spasm and a cyclic third nerve palsy must be
      considered as differential diagnoses. The case of a 32-year-old woman suffering
      from intermittent diplopia six months after radiation therapy of a recurrent
      pituary gland adenoma is presented.

PMID- 12221491
TI  - The molecular basis of the congenital fibrosis syndromes.
AB  - The congenital fibrosis syndromes (CFS) are rare inherited strabismus syndromes
      that present as congenital, nonprogressive ophthalmoplegias with active and
      passive restriction of globe movement, and include classic and atypical forms of
      congenital fibrosis of the extraocular muscles (CFEOM) and Duane syndrome (DS).
      Although historically believed to result from primary extraocular muscle
      fibrosis, both neuropathologic and genetic studies support the hypothesis that
      these disorders result from aberrant development of motor nuclei in the midbrain
      and pons.

PMID- 12221492
TI  - High resolution fMRI of ocular dominance columns within the visual cortex of
      human amblyopes.
AB  - Non-human primate models suggest that amblyopia has a neural basis in the form of
      a massive reduction in binocular neurons, and in some cases, a shift in ocular
      dominance of neural activity toward the unaffected eye. To date, the resolution
      of neuroimaging has been insufficient to investigate the neural basis of ocular
      dominance in human amblyopia. We used high spatial resolution (0.5 x 0.5 x 3 mm)
      functional magnetic resonance imaging (fMRI) to obtain maps of ocular dominance
      within the visual cortex of adult human amblyopes. fMRI maps of ocular dominance
      were similar in appearance to maps reported in the literature. For each of six
      adults with early-onset amblyopia, the number of map pixels corresponding to the
      unaffected eye was greater than the number corresponding to the amblyopic eye.
      This shift in ocular dominance was not seen for the two adults with later-onset
      amblyopia, suggesting that a shift in ocular dominance of neural activity occurs
      only if amblyopia onset is within the critical period of brain development. Our
      findings demonstrate how fMRI can non-invasively investigate the neural
      substrates underlying human amblyopia at the cortical column level.

PMID- 12221493
TI  - The topographic diagnosis of acquired nystagmus in brainstem disorders.
AB  - Evidence is presented for a clinical classification of central vestibular
      syndromes according to the three major planes of action of the vestibulo-ocular
      reflex (VOR): yaw, pitch, and roll. The plane-specific vestibular syndromes are
      determined by ocular motor, postural, and perceptual signs. Yaw plane signs are
      horizontal nystagmus, horizontal past pointing, rotational and lateral body falls
      to the right or to the left, and horizontal deviation of perceived straight
      ahead. Pitch plane signs are upbeat/downbeat nystagmus, forward/backward tilts
      and falls, and upward or downward deviations of the perceived horizontal. Roll
      plane signs are torsional nystagmus, skew deviation, ocular torsion, tilts of
      head, body, and perceived subjective visual vertical. The VOR syndromes defined
      in this way allow a precise topographic analysis of brainstem lesions according
      to their level and side. The lesional sites of yaw syndromes are restricted to
      the pontomedullary level (vestibular nucleus). A tone imbalance in pitch
      indicates bilateral (paramedian) lesions of the medullary or pontomesencephalic
      brainstem or bilateral dysfunction of the flocculus. A tone imbalance in roll
      indicates unilateral lesions, ipsiversive at the pontomedullary level (vestibular
      nuclei) and contraversive at the pontomesencephalic level (MLF and INC). A
      unilateral lesion (or stimulation) of the graviceptive pathways, which transduce
      input from vertical semicircular canals and otolith, affects function in roll,
      whereas bilateral lesions affect function in pitch.

PMID- 12221494
TI  - Genetics of isolated and syndromic strabismus: facts and perspectives.
AB  - Family studies have demonstrated the genetic etiology of concomitant strabismus
      (prevalence in different populations 1-5%, positive family history in 37% on
      average), as have twin studies (mean concordance in monozygous twins 73% compared
      to 35% in dizygous twins). In Duane's syndrome, three chromosomal loci have been
      identified to date: 2q31, 8q13, and 22q11; loci have also been identified in
      Moebius syndrome (various inheritance patterns): 13q12.2-q13, 3q21-q22, and
      10q21.3-q22, as well as in congenital fibrosis of the extraocular muscles (CFEOM;
      3 loci, 1 gene).(1) Already identified are the genes for a number of rarer
      muscular dystrophy syndromes with ocular involvement, various forms of congenital
      myasthenia, and mitochondrial diseases (with the primary defect located either in
      the mtDNA, resulting in a mitochondrial inheritance pattern, or in the nuclear
      DNA with Mendelian inheritance). A number of hereditary retinal diseases
      (Mendelian inheritance) may also be associated with strabismus. More than one
      gene is likely to be involved in the frequently occurring concomitant strabismus,
      making the analysis more difficult. Patients with chromosomal rearrangements,
      large families and isolated populations (see also the contributions by Preising
      and Zitzlsperger et al. in this issue)(2,3) will be instrumental in gene
      identification. In view of the high prevalence of concomitant strabismus, the
      disclosure of its etiology will have considerable medical, psychosocial and
      health-cost impact.

PMID- 12221495
TI  - Towards identification of genes in regionally accumulated strabismus.
AB  - Strabismus, as an inherited disease, is a new challenge to the geneticist.
      Various forms of strabismus can be found in distantly related members of the same
      family, who usually report to local ophthalmologists and orthoptic centers very
      rarely. In addition, local ophthalmologists and orthoptic centers very rarely pay
      attention to the genetic aspects of strabismus. Therefore, the recruitment of
      suitable families to identify the underlying genes is the major drawback in this
      effort. Further problems arise from the mode of inheritance, which can formally
      be characterized as autosomal dominant with reduced penetrance in most families,
      but should be considered as multifactorial inheritance with a threshold
      combination of mutated alleles. The present paper deals with a method for using
      local accumulations of strabismus patients to circumvent the problems of small
      families and rare numbers of affected persons. The steps on the way to the
      identification of strabismus genes will be described.

PMID- 12221496
TI  - In search for increased prevalence rates of strabismus and microstrabismus in two
      Bavarian districts, Oberpfalz and Niederbayern, to spot populations for gene
      identification.
AB  - PURPOSE: This study was intended to identify communities with an increased
      prevalence rate of inherited eye diseases (different forms of strabismus,
      juvenile maculopathy, AMD, myopia magna, etc.) in the districts Oberpfalz (Opf.)
      and Niederbayern (Ndb.). The data obtained in this study will serve to identify
      larger families and inbred populations for genetic testing to identify the cause
      of eye diseases with autosomal recessive and multifactorial inheritance. DESIGN:
      In cooperation with the local ophthalmologists in two Bavarian districts
      anonymized lists were compiled correlating diagnosis, postal code, and
      municipality of strabismus patients. The office software used in the
      participating practices was a limiting factor as well as the hand-written records
      used in most of these. The collected data were correlated with the published
      prevalence rates in the general population. RESULTS: Of the 104 local
      ophthalmologists who were invited to participate, only 17 provided information.
      The results indicate an increased prevalence rate of strabismus and
      microstrabismus patients from Neumarkt (Opf.) / Postbauer-Heng, Amberg,
      Hauzenberg and Pocking. CONCLUSION: Documentation as it is currently done - local
      ophthalmologist generally have written records and computer systems that are
      unsuitable for detailed surveys - restricts the possibility of completing the
      survey in the whole area. Nevertheless, regional accumulations of
      strabismus/microstrabismus could be described, providing populations for further
      investigations to uncover the genetic causes.

PMID- 12221497
TI  - Grating acuity with varying field size in patients and normal infants.
AB  - PURPOSE: To investigate the effect of field size on grating acuity assessment in
      normal children and pediatric ophthalmological patients. METHOD: A prototype set
      of acuity cards was produced with three acuity steps per octave and a card size
      of 26 x 70 cm, bearing a grating field of 26 x 35 cm. Field size reduction was
      achieved by masking. Large fields of the prototype versus TAC-sized fields were
      tested in normal infants and ophthalmological patients. RESULTS: Teller acuity
      cards (TAC) and masked prototype cards of equal field size gave identical results
      in normal controls and pediatric ophthalmological patients. A better response to
      large fields was found in all normal infants up to 7 months of age and in none
      older than 15 months. In patients, an effect of field size was found in
      decreasing numbers up to 5 years of age. The interocular acuity difference was
      larger when small fields were presented. CONCLUSION: The effect of field size in
      patients is considered to be a developmental delay due to the individual history
      of disease. It may possibly have prognostic value for treatment.

PMID- 12221498
TI  - Nystagmus in suprasellar tumors: recent advances in diagnosis and therapy.
AB  - Congenital and acquired nystagmus, particularly pendular and jerk nystagmus, see
      saw nystagmus and spasmus nutans, may be the presenting sign of a suprasellar
      mass lesion.(1) The large variety of different suprasellar mass lesions requiring
      quite different therapeutic measures necessitates exact histological diagnosis
      for optimal therapeutic strategy planning.(2) Stereotactic tumor biopsy has
      become a well-established diagnostic approach, combining minimal surgical trauma
      with a high degree of diagnostic safety. Particularly in the two most frequent
      suprasellar mass lesions - craniopharyngiomas and pilocytic astrocytomas -
      accurately planned stereotactic drainage of tumor cysts combined with
      radiotherapy and/or stereotactic radiosurgery allows successful decompression and
      tumor control as well as maximum preservation of visual and endocrinological
      functions when compared with conventional surgical procedures.(2-11)

PMID- 12221499
TI  - Visual and perceptual characteristics, ocular motility and strabismus in children
      with periventricular leukomalacia.
AB  - The immature visual system is vulnerable to adverse events. Periventricular
      leukomalacia (PVL), an end-stage lesion after hypoxia-ischemia at gestational age
      24-34 weeks affecting the visual radiation, has become a principal cause of
      visual impairment in children. Cerebral visual dysfunction caused by PVL is
      characterized by delayed visual maturation, subnormal visual acuity, crowding,
      visual field defects, and visual perceptual-cognitive problems. Magnetic
      resonance imaging is the method of choice for diagnosing this brain lesion, which
      is associated with optic disk abnormalities, strabismus, nystagmus, and deficient
      visually guided eye movements. Children with PVL may present to the
      ophthalmologist within a clinical spectrum from severe visual impairment in
      combination with cerebral palsy to only early-onset esotropia, normal
      intellectual level and no cerebral palsy. Optimal educational and habilitational
      strategies need to be developed to meet the needs for this group of children.

PMID- 12221500
TI  - Philosophical challenges in teaching bioethics: the importance of professional
      medical ethics and its history for bioethics.
AB  - The papers in this number of the Journal originated in a session sponsored by the
      American Philosophical Association's Committee on Philosophy and Medicine in
      1999. The four papers and two commentaries identify and address philosophical
      challenges of how we should understand and teach bioethics in the liberal arts
      and health professions settings. In the course of introducing the six papers,
      this article explores themes these papers raise, especially the relationship
      among professional medical ethics, the "long history" of medical ethics, and
      bioethics. The tendency of bioethics to deprofessionalize medical ethics is
      rejected, in favor of an historically informed professional medical ethics. It is
      suggested that bioethics should be critically reconsidered from the perspective
      of medical ethics as professional ethics.

PMID- 12221501
TI  - What conception of moral truth works in bioethics?
AB  - For the most part, philosophers have regarded moral truth as propositional and as
      what follows from the application of moral theory to particular problematic
      cases. Here I maintain that this is not a useful way of conceiving moral truth in
      bioethics. Rather, we are better off conceiving of moral truth as what emerges
      from a process of inquiry conducted in a certain manner. There are four elements
      to this process: (1) careful exploration of the embedded norms of medical
      practice, research, and delivery; (2) recognition of the irreducible plurality of
      ultimate moral values within and between these practices; (3) the cultivation and
      exercise of moral imagination; and (4) the attainment, however temporarily, of
      wide reflective equilibrium. This process, I argue, is reflected in the way
      bioethics is most fruitfully practiced, and it is further to be recommended by
      being true to the character of moral conscientiousness generally. This analysis
      suggests that moral truth is "unstable," but that this is not a bad thing.
      Further, the implication is drawn that moral theory would be better informed if
      formulated on the basis of paying more attention to lived moral practices.

PMID- 12221502
TI  - Teaching bioethics in the new millennium: holding theories accountable to actual
      practices and real people.
AB  - Teaching bioethics in the new millennium requires its practitioners to confront a
      wide area of methodological alternatives. This essay chronicles the author's
      journey from the principlism of Beauchamp and Childress, through narrative and
      postmodern bioethics, to a complex feminist critique of postmodern bioethics that
      emphasizes functional human capabilities and the creation of structures that can
      facilitate free discussion of those capabilities and how best to realize them.
      Teaching bioethics concerns not only the acknowledgement of differences but also
      reminding ourselves of our samenesses. Sustained Habermasian democratic
      conversations might help us to escape the narrow confines of a postmodern
      bioethics of moral strangers for a richer world of moral friends.

PMID- 12221503
TI  - Teaching bioethics at (or near) the bedside.
AB  - Many teachers of bioethics often express concern, in their writings and
      otherwise, about the theoretical basis (or lack of it) of bioethics and the
      allied issue of relativism. The companion articles by Tong and Momeyer are in
      this vein and rightly address such issues within the context of a liberal arts
      education. This article addresses such issues in a different venue, i.e.,
      bioethics teaching in the clinical sphere of health care institutions. It
      presumes to suggest that many of these theoretical concerns, as well as the
      threat of relativism, seldom arise in this sphere. Rather, a broad based, well
      accepted body of moral truth has been fashioned over the last quarter century and
      it is this that clinical bioethics regularly keys to and to which most moral
      dilemmas are referred for resolution. The various forms of this pedagogy, e.g.,
      case consultations or institutional policy statements, are charted out in this
      regard, as well as the often tactical character of much of this teaching, i.e.,
      not "what should we do?", but "how might we best do it?". The article then goes
      on to conclude with a reflection on the use and abuse of power in clinical
      bioethics teaching and consultation.

PMID- 12221504
TI  - Bioethics and history.
AB  - Standard bioethics textbooks present the field to students and non-experts as a
      form of "applied ethics." This ahistoric and rationalistic presentation is
      similar to that used in philosophy of science textbooks until three decades ago.
      Thomas Kuhn famously critiqued this self-conception of the philosophy of science,
      persuading the field that it would become deeper, richer, and more philosophical,
      if it integrated the history of science, especially the history of scientific
      change, into its self-conception. This essay urges a similar reconceptualization
      for bioethics, arguing that the analysis of moral change ought to be integral to
      bioethics (and to ethics generally). It proceeds by suggesting the sterility of
      the ahistoric, rationalist applied ethics model of bioethics embraced by standard
      bioethics textbooks. It also suggests the fecundity of alternative conceptions of
      the bioethics that focus on the history of successful and failed attempts to
      negotiate moral change, and the history of multifaceted relations between moral
      philosophy and practical ethics.

PMID- 12221505
TI  - The meanings of professional life: teaching across the health professions.
AB  - Most of professional ethics is grounded on the assumption that we can speak
      meaningfully about particular, insulated professions with aims and goals, that
      conceptually there exists a clear "inside and outside" to any given profession.
      Professional ethics has also inherited the two-part assumption from mainstream
      moral philosophy that we can speak meaningfully about agent-relative versus agent
      neutral moral perspectives, and further, that it is only from the agent-neutral
      perspective that we can truly evaluate our professional moral aims, rules, and
      practices. Several important changes that have occurred, or are currently taking
      place, in the structure of the health care professions, challenge those
      assumptions and signal the need for teachers of professional ethics to rethink
      the content of what we teach as well as our teaching methods. The changes
      include: influences and critique from other professions and from those who are
      served by the health professions, and influences and critique from professionals
      themselves, including increased activism and dissent from within the professions.
      The discussion focuses on changes that have occurred in the health-related
      fields, but insofar as similar changes are occurring in other professions such as
      law and business, these arguments will have broader conceptual implications for
      the way we ought to think about professional ethics more generally.

PMID- 12221506
TI  - Two concepts of medical ethics and their implications for medical ethics
      education.
AB  - People who discuss medical ethics or bioethics come to very different conclusions
      about the levels of agreement in the field and the implications of consensus
      among health care professionals. In this paper I argue that these disagreements
      turn on a confusion of two distinct senses of medical ethics. I differentiate (1)
      medical ethics as a subject in applied ethics from (2) medical ethics as the
      professional moral commitments of health care professions. I then use the
      distinction to explain its significant implications for medical ethics education.
      Drawing on the recent work of John Rawls, I also show the centrality of
      philosophy in medical ethics by illustrating how contemporary philosophy can be
      used to construct an ethical framework for the medical professions.

PMID- 12221507
TI  - Comparative morphology and biochemistry of pancreatic tissue fragments
      transplanted into the anterior eye chamber and subcutaneous regions of the rat.
AB  - The present study was designed to compare the morphological changes occurring in
      pancreatic tissue fragments transplanted into the anterior eye chamber (AEC) and
      the subcutaneous (SC) regions of the rat. Pancreatic tissue segments were removed
      from the tail end of the pancreas of neonatal rats and transplanted into the AEC
      and SC region of the neck of homologous rats. Five weeks after transplantation,
      the grafts were removed and processed for light microscopy, immunohistochemistry
      and radioimmunoassay. In both pancreatic tissue grafts, the acinar cells
      degenerated completely after transplantation. In contrast to this, insulin-,
      glucagon-, somatostatin- and pancreatic polypeptide-positive cells and pancreatic
      ducts survived equally well in both the AEC and SC grafts. The pattern and
      percentage distribution of insulin-, glucagon-, somatostatin- and PP-producing
      cells in the AEC and SC grafts was similar to that observed in normal pancreas.
      However, the percentage distribution of glucagon- and PP-containing cells was
      significantly (p < 0.03) lower in SC grafts when compared to normal.
      Radioimmunoassay showed that the AEC and SC pancreatic tissue grafts contained
      large quantities of insulin and glucagon. However, the insulin content of AEC was
      slightly but not significantly higher than that of SC grafts. The protein content
      of pancreatic tissue grafts in these transplantation sites was still
      significantly (p < 0.05) lower compared to normal. Lymphatic infiltration was
      also more conspicuous in SC grafts compared to AEC grafts. This infiltration by
      lymphatic cells was confined only to the endocrine portion of the graft. In
      conclusion, pancreatic tissue grafts survived in both the AEC and SC regions of
      rats but the AEC appears to be more conducive to graft survival than the SC
      region.

PMID- 12221508
TI  - Differentiation of ciliated cells in the terminal bronchioles of neonatal calves.
AB  - The bronchiolar ciliated cells are exquisitely sensitive to injury caused by
      infection or irritation of the airways. The mechanism by which bronchiolar
      ciliated cells are renewed following injury or during the normal course of
      differentiation is still debated. The present study aimed at recognizing the
      progenitor cell population for bronchiolar ciliated cells during early neonatal
      life of calves and to demonstrate the course of events occurs during its
      differentiation into ciliated cells. Scanning electron microscopy of the terminal
      bronchiolar epithelium revealed two distinct cell types namely ciliated and non
      ciliated cells. Transmission electron microscopy revealed ciliated, non-ciliated
      (Clara), intermediate and basal cells. At least two categories of intermediate
      cells could be distinguished: intermediate cells with abundant glycogen and
      variable numbers of organelles; intermediate cells with little glycogen, large
      numbers of polyribosomes, and variable numbers of basal bodies. We conclude that:
      (1) both bronchiolar non-ciliated and basal cells serve as progenitors for the
      bronchiolar ciliated cells; (2) differentiation of ciliated cell from the non
      ciliated one involves a transitional cell in which glycogen is lost,
      polyribosomes are synthesized before the synthesis of basal bodies and cilia.

PMID- 12221509
TI  - The ultrastructure of primary cilia in the endocrine and excretory duct cells of
      the pancreas of mice and rats.
AB  - A primary cilium was frequently observed in the endocrine alpha, beta and delta
      cells, as well as in the excretory duct cells of the pancreas of normal mice and
      rats. The characteristic components of the cilium including the basal body,
      axoneme (shaft), and terminal part were clearly recognizable. The basal body or
      distal centriole surrounded by Golgi vesicles was perpendicularly oriented to the
      proximal centriole, and a dense striated band was seen filling the gap between
      them. The microtubules of the basal body consisted of nine peripheral triplets
      exhibiting a 9 + 0 pattern, an appearance similar to that of the proximal
      centriole. Rootlets, basal feet and alar sheets associated with the basal body
      were occasionally seen. The axoneme usually consisted of a 9 + 0 pattern of
      microtubule doublets, but other irregular patterns of 7 + 2, 7 + 3, and 8 + 1
      were also seen. The microtubules in the terminal part of the cilium became fewer
      in number and had no peculiar arrangement. The cilium of the endocrine cells
      always projected into the intercellular canaliculus and was covered by the
      ciliary sheath, and occasionally, double cilia were visualized in the vicinity of
      beta cells. In the excretory duct cells, the cilium showed similar features, but
      it was slightly longer and always projected into the dense secretory content of
      duct lumen. On the other hand, no primary cilium was ever observed in the acinar
      cells of mouse and rat pancreas. In conclusion, the present study describes the
      morphology of primary cilia and its associated components in the endocrine and
      excretory duct cells of the pancreas of mice and rats. The findings suggest that
      the primary cilium should be considered as a constant intracellular organelle
      though its function and significance remain speculative.

PMID- 12221510
TI  - Olfactory mucosa ultrastructure in the short-tailed shrews, Blarina brevicauda
      and Blarina carolinensis.
AB  - The olfactory mucosae of the northern short-tailed shrew, Blarina brevicauda, and
      the southern short-tailed shrew, Blarina carolinensis, were examined by light and
      electron microscopy. A well-developed olfactory epithelium was observed that
      included all of the cells necessary to provide for a sensitive olfactory system,
      suggesting that olfaction plays a major role in the behavior of these animals.
      There were no significant differences between the olfactory mucosae of these two
      species. The general features of the olfactory epithelium in these shrews were
      similar to those reported for several other macrosmatic mammals. A new type of
      supporting cell, called the light supporting cell, was observed in these shrews.
      The light supporting cell cytoplasm exhibited very little staining by light
      microscopy and had low electron density by transmission electron microscopy
      compared to that of the more common dark supporting cell. The light supporting
      cell had a convex apical surface with microvilli and lacked the large amounts of
      smooth endoplasmic reticulum (SER) typical of the apical cytoplasm of the dark
      supporting cell. In the lamina propria of the mucosa, the Bowman's glands
      consisted of two cell types, one with electron-lucent, alcian blue-positive
      granules, and the other with electron-dense PAS-positive granules. The cell with
      electron-lucent granules contained large amounts of SER and small clumps of rough
      ER. The cells with electron-dense granules had large amounts of RER and little
      SER.

PMID- 12221511
TI  - A fourth teleost lineage possessing extra-oral teeth: the genus atherion
      (teleostei; atheriniformes).
AB  - In the course of an evolutionary and developmental study on the dermal skeleton,
      our attention was drawn to the existence of denticles located outside the oral
      cavity in the atheriniform species Atherion elymus. These denticles, attached to
      the surface of most dermal bones of the head, are especially numerous on the
      snout, chin and the undersides of the lower region of the head, where they are
      aligned forming a crenulated keel. Using light, scanning and transmission
      electron microscopy, we clearly demonstrate the dental (vs bony) nature of these
      denticles. They are small, conical elements mostly oriented backwards and are not
      ankylosed to the bone support. Ligaments originating from the internal and
      external surface of the base of the dentine cone link the denticles to the
      attachment bone, which itself merges with the bone support below. The denticles
      have the same form and structure as teeth, from which they differ only in having
      a larger base and a pulp cavity that is nearly completely filled with secondary
      dentine by centripetal deposition. This suggests that the denticles have a longer
      functional history than teeth. Atherion is now the fourth teleost lineage found
      to develop such denticles on the head.

PMID- 12221512
TI  - Plastination of dissected brain specimens and Mulligan-stained sections of the
      human brain.
AB  - The difficulties in obtaining human brain material for teaching neuroanatomy have
      increased the demand for more durable brain specimens. In this paper, we describe
      results obtained by preparing large, plastinated, dissected human brain specimens
      and Mulligan-stained sections of the human brain. The brains were fixed in
      formalin, washed and dissected in order to visualize the fibre tracts and larger
      nuclei in the central nervous system. This was followed by dehydration at -20
      degrees C in acetone. The specimens were then impregnated with silicone, Biodur
      S10, in vacuo and hardened in Biodur S6 vapour. The grey and white substance in
      the central nervous system as well as the larger fibre tracts and nuclei were
      clearly visible in the dissected, plastinated specimens. Coronal and sagittal
      sections of the human brain were stained according to Tompsett's modification of
      the Mulligan method. The sections were then dehydrated in cold acetone followed
      by forced impregnation with Biodur S10 and hardening. The plastinated sections
      stained distinctly and strongly and the nuclei in the forebrain, cerebellum and
      brain stem could be identified easily. The sections did not fade when exposed to
      light and could be easily handled in the classroom without damage. Therefore, the
      distinct visualization of neuroanatomical structures, the improved durability of
      the specimens, as well as the lack of odour make plastinated specimens and
      stained sections of the central nervous system a valuable tool for teaching
      neuroanatomy that compliments the use of wet preparations.

PMID- 12221513
TI  - Rapid polymerisation with microwave irradiation for transmission electron
      microscopy.
AB  - Successful results of microwave polymerisation of different epoxy formulations
      have been reported in the literature. The present study was intended to shorten
      the time needed for polymerisation of epoxy resin by the use of a microwave
      technique. A standard double fixation and tissue processing was applied to
      samples of rat kidney tissue. Tissue samples from the control group were
      polymerised in a conventional oven at 60 degrees C for 48 h, while tissue from
      the experimental group was irradiated in a microwave oven, initially at 900 W for
      10 min and then at 360 W for another 100 min. During this irradiation, the sealed
      BEEM capsules were submerged in a water bath, so that the temperature rise was
      uniform and constant. This resulted in a homogeneous and rapid polymerisation.
      The cutting properties of the blocks in both groups were similar and no
      noticeable difference in the quality of the sections was evident when evaluated
      with TEM. The results showed that the use of a microwave oven reduced the time
      needed for the polymerisation of Epon blocks without any loss in quality.

PMID- 12221514
TI  - The enthesis of the elbow-joint capsule of the dog humerus.
AB  - The enthesis of the elbow-joint capsule in the dog is described histologically in
      relation to the specific mechanical forces that operate in different regions
      along its line of attachment. Special attention is given to the collagen fibre
      bone interface in those parts of the capsule that are highly affected by
      mechanical stress. The histological features of the enthesis are heterogeneous
      along the entire circumference of the attachment site. Three types of collagen
      fibre-bone interconnections can be distinguished: (1) periosteal insertion:
      attachment to the periosteum of the humerus; (2) bony insertion: attachment
      directly to peripheral osteons; (3) fibrocartilaginous insertion: attachment to
      the bone via fibrocartilage. The periosteal insertion covers the greatest part of
      the joint capsule attachment line, along the peripheral borders of the radial and
      olecranon fossae. In contrast, bony insertions and fibrocartilaginous insertions
      are focally arranged: bony insertions in the caudoproximal aspect of the
      olecranon fossa, related to nutrient foramina; fibrocartilaginous insertions in
      combination with the attachment of distinct ligaments. This distribution reflects
      a strict relation between the type of enthesis and the biomechanical stress at
      the attachment site. The periosteal insertion type is predominant in entheses
      adjacent to pouches of a loose joint capsule -- i.e., regions less dependent on
      the high tensile strength of collagen fibres. Fibrocartilaginous insertions
      characterise areas of the joint capsule which are subjected to high biomechanical
      traction during joint movement. Both structurally and functionally, the entheses
      of the fibrous layer of the joint capsule are similar to those of tendons and
      ligaments.

PMID- 12221516
TI  - The influence of fetoabdominal tissues on fetal ECGs and MCGs.
AB  - Both fetal electrocardiography and fetal magnetocardiography are influenced by
      the volume conduction within the abdomen of the pregnant woman. In this paper,
      various models are used to simulate this influence. Such models are helpful to
      determine where to attach electrodes at the maternal abdomen in case fetal ECGs
      are measured and where to position the magnetocardiograph in case fetal MCGs are
      measured. Another goal is to assess the influence of individual differences, such
      as the amount of amniotic fluid. Seven models based on MR-images have been
      created, four for the third trimester of gestation, with the fetus in left
      occiput position, and three for the second trimester. The models consist of four
      compartments; the fetus, the vernix caseosa, the amniotic fluid, and the
      remainder of the maternal abdomen. It turns out that individual differences have
      a large impact on the fetal MCG and that the best measurement positions are
      expected over the centre of the abdomen near the fetal heart. The fetal ECG is
      dependent on the vernix caseosa and when this layer is present, the fetal ECG is
      best measured by two electrodes, one over the fetal mouth and the other over the
      bottom of the fetus.

PMID- 12221517
TI  - Intrinsic properties inhibit axonal outgrowth from neonatal rat spinal cord
      explant.
AB  - Lumbar spinal cord explants, harvested from neonatal rat pups aged between
      postnatal day 0 (P0) and P6, were cultured for a period of 48 hrs in the
      chemically defined medium R(12) on a poly-ethylene-imine (PEI) and on poly-D
      lysin (PDL) coated surface. The outgrowth outside the explant was quantified.
      Lumbar explants from the same rat and embedded in a collagen matrix, and cortical
      explants from a P0 rat were used as controls. Statistical analysis demonstrated a
      clear relation between age-at-explantation and the number of neurites in the
      corona surrounding the explant. The number of outgrowing neurites decreased
      sharply with age-at-explantation. The average number of neurites per explant
      obeyed to the expression log (n) = -0.736x + 3.294 on PEI, and log (n) = -0.721x
      + 2.295 on PDL; x epsilon in [P0 - P6] (n, the number of neurites per explant; x,
      the age-at-explantation expressed in postnatal days). A similar observed age
      related decrease of outgrowth has been described when culturing the lumbar
      explant inside a collagen matrix. The phenomenon appears to be an intrinsic
      property of the explant. We review growth inhibitory properties in different
      models and propose that the phenomenon occurs here at the interface explant
      world.

PMID- 12221518
TI  - A case of a de novo A3243G mutation in mitochondrial DNA in a patient with
      diabetes and deafness.
AB  - A female individual with symptoms of the Maternally Inherited Diabetes and
      Deafness syndrome (MIDD) was diagnosed positive for the A3243G mutation in her
      mitochondrial DNA. Heteroplasmy levels were 18% in DNA from leucocytes and 55% in
      oral mucosa DNA. This finding corroborates the diagnosis of MIDD. Normally, this
      mutation is present in all the individuals within the maternal lineage of the
      pedigree. In this particular pedigree the mutation was undetectable in the mother
      of the proband and her three brothers. Paternity testing using polymorphic
      chromosomal DNA markers supported the assumed family relationship. We conclude
      that we are dealing in this proband with the de novo appearance of the A3243G
      mutation that has reached high heteroplasmy values in at least two tissues within
      one generation. This observation supports the hypothesis that during
      embryogenesis mitochondrial DNA goes through a genetic bottleneck with a limited
      number of segregating units.

PMID- 12221519
TI  - Influence of fasting on the effects of ischemic preconditioning in the ischemic
      reperfused rat heart.
AB  - The effects of fasting and ischemic preconditioning (IP) on heart function of
      Langendorff-perfused rat hearts exposed to 25 min global ischemia plus 30 min
      reperfusion (RP), were correlated with lactate release and tissue-levels of long
      chain acyl carnitine (LCCa) and CoA (LCCoA). IP was achieved by a 3 min ischemia
      plus a 5 min reperfusion cycle. Creatine kinase leakage was measured to assess
      the extent of cardiac injury. Fasting reduced the ischemic-induced contracture,
      improved RP recovery of mechanical function, reduced lactate release and
      increased the end-ischemia LCCoA and LCCa levels. Both in the fed and the fasted
      rat hearts IP delayed the pacemaker depression, reduced the amplitude of ischemic
      contracture and improved the RP recovery of contraction. However, IP reduced
      creatine kinase and lactate release only in the fed rat hearts. IP had no effects
      on tissue LCCa and LCCoA in both groups. These data suggest that: 1) beneficial
      effects of fasting may be ascribed, at least in part, to a reduced lactate
      production which may attenuate ischemic myocyte acidification and to the
      accumulation of fatty acyl esters which would favour citric acid cycle
      replenishment during RP. 2) beneficial effects of IP could be in part explained
      by the reduction of lactate production in the fed group although data obtained
      with the fasted rat heart indicate that another mechanisms must also be involved
      in the effects of IP. 3) accumulation of LCCoA and LCCa is not involved in the
      noxious effects of ischemia as well as in the protection effected by IP.

PMID- 12221520
TI  - Tauroursodeoxycholic acid reduces damaging effects of taurodeoxycholic acid on
      fundus gastric mucosa.
AB  - We investigated the effects of tauroursodeoxycholic acid (TUDCA) to assess
      whether this acid may also have "protective" effects similar to those found with
      ursodeoxycholic acid (UDCA). We used a well-known amphibian model of gastric
      mucosa, and studied the effects of taurodeoxycholic acid (TDCA) on electrical
      transepithelial parameters, acid secretion and histology in absence or in
      presence of TUDCA. Mucosal exposure to TDCA, after stimulation with histamine,
      caused a reduction in transepithelial potential difference (V(t)) and
      transepithelial resistance (R(t)) and a decrease in acid secretion while mucosal
      exposure to TUDCA did not cause a significant change in the electrical
      parameters. Moreover, TDCA primarily affected the neck cells, while TUDCA
      affected only oxyntic cells, causing a similar degree of injury to that observed
      in controls. Mucosal exposure to TUDCA plus TDCA caused a reduction in short
      circuit current (I(sc)) and R(t), whereas acid secretion did not change. These
      results suggest that: (1) TUDCA reduces the damaging effects of TDCA on fundus
      gastric mucosa; (2) TUDCA may play an important role in the treatment of
      gastritis associated with bile reflux.

PMID- 12221521
TI  - Effect of microwave electromagnetic field on skeletal muscle fibre activity.
AB  - The aim of the present study was to investigate the influence of microwave
      irradiation on fatiguing activity of isolated frog skeletal muscle fibres. The
      changes in the electrical and mechanical activity were used as criteria for the
      exposure effects. Repetitive suprathreshold stimulation with interstimulus
      interval of 200 ms for 3 min was applied. Intracellular (ICAP) and extracellular
      (ECAP) action potentials and twitch contractions (Tw) of muscle fibres after 1
      hour microwave exposure (2.45 GHz, 20 mW/cm( 2) power density) were compared with
      those recorded after one hour sham exposure (control). The duration of
      uninterrupted activity in the trial (endurance time; ET) was not significantly
      affected by microwave field exposure. After microwave irradiation, the ICAP
      amplitude was higher, the rising time was shorter, and the resting membrane
      potential was more negative compared to controls. There was a slower rate of
      parameters changes during ET in potentials obtained from irradiated fibres.
      Microwave exposure increased the propagation velocity of excitation, the ECAP and
      Tw amplitudes, as well as shortened their time parameters. We concluded that a
      2.45 GHz microwave field possesses a stimulating effect on muscle fibre activity,
      which is in part due to its specific, non-thermal properties. The microwave
      induced-changes in muscle fibre activity may reduce development of skeletal
      muscle fatigue.

PMID- 12221523
TI  - Critical role of photoreceptor apoptosis in functional damage after retinal
      detachment.
AB  - PURPOSE: Although apoptosis is assumed to play a pivotal role in retinal function
      loss, its mechanism and real influence on retinal function are still unclear. To
      investigate the relation between retinal function and apoptosis, we studied
      photoreceptor apoptosis in experimental retinal detachment (RD). METHODS: We
      induced RD by subretinal injection of sodium hyaluronate in Brown Norway rats.
      Apoptotic photoreceptors were detected by TdT-dUTP Terminal Nick-End Labeling
      (TUNEL). To evaluate the function of the detached retina, electroretinograms
      (ERGs) were taken on day 1, 3 with corneal electrodes and full-field stimulation.
      RESULTS: Apoptotic DNA fragmentation appeared 12 hours after RD, was most
      prominent on day 3, and decreased thereafter. The ERGs showed that the amplitudes
      of dark-adapted a-waves and light adapted 2 Hz b-waves decreased immediately
      after RD and continued to decrease over time. The administration of Fas/Fc
      chimera recombinant protein or a caspase inhibitor, Z-VAD.fmk, failed to prevent
      either photoreceptor apoptosis or retinal functional damage. In contrast, brain
      derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF)
      significantly impeded both apoptosis and dysfunction. The ERGs recognized the
      functional changes sensitively, and these ERG changes correlated well to the
      amount of photoreceptor apoptosis. Immunohistochemical study showed that
      apoptosis-inducing factor (AIF), a novel caspase-independent apoptotic factor,
      was relocalized from mitochondria to the nucleus in this process. CONCLUSIONS:
      The present results showed that apoptosis was a key phenomenon in the retinal
      dysfunction in RD and that this process was transmitted mainly by mitochondria
      dependent pathways rather than Fas/Fas-L or downstream caspase dependent
      pathways.

PMID- 12221524
TI  - (-)-Isoproterenol modulation of maxi-K(+) channel in nonpigmented ciliary
      epithelial cells through a G-protein gated pathway.
AB  - PURPOSE: Adrenergic agents decrease intraocular pressure by reducing aqueous
      humor secretion from ciliary epithelial cells. Since the ionic concentration of
      aqueous humor contributes to intraocular pressure, we have investigated the
      effect of (-)-isoproterenol, a beta-adrenergic agonist on the maxi-K( +) channel
      in rabbit nonpigmented ciliary epithelial (NPE) cells. METHODS: Single-channel
      currents were recorded from the basolateral surface of acutely isolated NPE cells
      using patch clamp techniques. RESULTS: A calcium dependent maxi-K(+) channel was
      identified in 31% of cell-attached patches. In the excised condition the channel
      was activated in presence of calcium. In symmetrical K(+) solution a linear
      current-voltage relationship and unitary conductance of 158 +/- 15 pS was
      observed. Replacing K(+) with Na(+) the current-voltage curve shifted to the
      right and approached a reversal potential for K( +) ( approximately -80 mV).
      Barium (2 mM) from the intracellular side or iberiotoxin (50 nM) from the
      extracellular side blocked the channel activity. In cell-attached patches, the
      beta-receptor agonist (-)-isoproterenol (2.5 microM) increased channel open
      probability (P(o)) only when applied directly through the patch pipette. beta(2)
      adrenoceptor antagonists (ICI-118, 551, l-timolol) blocked the channel activity
      more efficiently than the beta(1)-adrenoceptor antagonist betaxolol. In excised
      patches, (-)-isoproterenol increased baseline P(o) 5-fold (0.5 +/- 0.13) when GTP
      (100 microM) and GTPgammaS (100 microM) were present at the cytosolic surface of
      the pipette (control; P(o), 0.12 +/- 0.006). GTP augmented baseline channel
      activity (0.1 +/- 0.004) 7-fold (0.7 +/- 0.03) when (-)-isoproterenol was
      included in patch pipette. CONCLUSIONS: Rabbit NPE cells expressed maxi-K(+)
      channels on their basolateral surface. The adrenergic agonist (-)-isoproterenol
      activated these channels via a beta(2)-adrenoceptor that was modulated by a
      direct G-protein gated pathway.

PMID- 12221525
TI  - Presence of CFTR in the conjunctival epithelium.
AB  - PURPOSE: To determine the presence of the cystic fibrosis transmembrane
      conductance regulator (CFTR) in the conjunctiva and examine the possibility of
      its regional expression in rabbit, rat and porcine conjunctival epithelia given
      distinct differences in morphological appearance between the bulbar and palpebral
      epithelia. METHODS: Two specific anti-CFTR antibodies, against different epitopes
      in the R domain of the CFTR molecule were used in immunofluorescent labeling of
      frozen fixed sections isolated from the bulbar and palpebral regions of fresh
      rabbit, porcine and rat conjunctivae. CFTR expression was also determined in the
      rabbit conjunctival epithelium using RT-PCR methods. RESULTS: CFTR
      immunoreactivity in the conjunctival epithelium exhibits polarized expression and
      is associated with the apical domain of conjunctival epithelial cells. An
      identical pattern of staining obtained in porcine cryosections using either of
      the anti-human CFTR antibodies confirmed the specificity of the positive apical
      staining. RT-PCR analysis produced bands at the predicted size for CFTR mRNA
      transcripts in both bulbar and palpebral portions of the rabbit conjunctival
      epithelium. CONCLUSIONS: Apical localization of CFTR in the conjunctival
      epithelium is consistent with the function of this protein as a chloride channel
      or as a regulator of channel activity. The identification of CFTR in both bulbar
      and palpebral portions of the conjunctiva provides evidence that the mechanisms
      for Cl secretion reside throughout the conjunctiva. This finding suggests that
      manipulations of the CFTR Cl channel could affect transepithelial Cl transport
      rates and water movement into the tear film.

PMID- 12221526
TI  - Investigating live and fixed epithelial and fibroblast cells by atomic force
      microscopy.
AB  - PURPOSE: To investigate the use of atomic force microscopy (AFM) to image live
      and fixed cell in culture. Rabbit corneal fibroblasts, Chang conjunctival cells,
      and transformed human corneal epithelial cells were chosen so that AFM parameters
      could be set for future use in toxicologic and pharmacologic studies of ocular
      cells. METHODS: Contact mode AFM was performed under air and in balanced salt
      solution (BSS) using live and fixed cells. All cell lines were imaged in the
      height mode for optimal resolution of cellular features. RESULTS: Images of fixed
      cells showed no discernible differences in surface features when visualized in
      air or under physiologic solution. Structural differences were observed, however,
      between fixed and live cells in BSS. Although the AFM technique provides high
      quality images of live cells under BSS, sub-membrane features of live cells are
      more well-defined compared to fixed cells. It was also possible to image live
      cells in air if imaging was completed within 10 minutes of removal of the cells
      from culture medium. Images of cytoskeletal features under air were similar to
      those obtained under BSS. CONCLUSIONS: The atomic force microscopy technique can
      be used to study cells and provide sub-cellular details at resolution equal to or
      in some situations better than the scanning electron microscopy technique.
      However, parameters for imaging have to be tailored for individual experimental
      goals.

PMID- 12221527
TI  - Human immunodeficiency virus type 2 (HIV-2) vector-mediated in vivo gene transfer
      into adult rabbit retina.
AB  - PURPOSE: To evaluate the potential usefulness of HIV-2 viral vector in in vivo
      retinal gene therapy. METHODS: An HIV-2 virus based viral vector was constructed
      and administered subretinally and intravitreally into rabbit eyes. After viral
      vector administration, the eyes were closely monitored for any adverse effects by
      slit lamp, indirect ophthalmoscopy, and fundus photography. Eyes were enucleated
      at specified times after injection, and reporter gene expression was identified
      within cell types and graded by the pattern and distribution of staining cells
      using fluorescent microscopy. RESULTS: The HIV-2 viral vector demonstrated
      efficient gene transfer into many types of retinal cells without apparent
      cytotoxicity. Notably with subretinal injection, the HIV-2 vector resulted in
      higher efficiency of transduction of photoreceptor cells than of the other cell
      types (p < 0.05). With the intravitreal administration of HIV-2 viral vectors,
      cellular transduction and transgene expression in the ganglion cell layer was the
      dominant finding. CONCLUSIONS: HIV-2 viral vector may be a useful gene delivery
      vehicle for retinal photoreceptor cells and ganglion cells. It deserves further
      exploration to investigate its potential merit in long term gene therapy
      protocols and in other animal species.

PMID- 12221528
TI  - Attenuation of ocular wall pulsation in eyes containing a gas bubble after
      vitrectomy.
AB  - PURPOSE: To evaluate the effect of an intraocular gas bubble on ocular wall
      pulsation. METHODS: Eight patients that underwent vitrectomy with intraocular gas
      injection for various reasons were studied. Ocular pulsation was evaluated in a
      semi-quantitative way by means of Goldman applanation tonometry in both eyes
      before and after the operation. Vitreous cavity gas fill in the operated eye was
      estimated by means of indirect ophthalmoscopy and was correlated with ocular
      pulsation. The follow up lasted until the gas totally disappeared. RESULTS:
      Ocular pulsation disappeared postoperatively in the operated eye and gradually
      reappeared when the gas fill diminished. Pulsation returned to preoperative level
      when the gas disappeared from the vitreous cavity. A negative statistical
      correlation between ocular pulsation and gas fill could be documented.
      CONCLUSION: The compressible nature of the intraocular gas bubble results in
      absorption of the vascular pulsation and prevents its transfer to the ocular
      wall. This leads to attenuation or even cancellation of ocular wall pulsation
      when a gas bubble exists within the eye.

PMID- 12221530
TI  - Simultaneous in vivo imaging of leukocyte migration: heterogeneity among iris,
      limbus, and choroid vessels.
AB  - PURPOSE: Endothelial cells of different vascular systems may express site
      specific adhesion molecules to attract leukocyte subsets. This study describes a
      method to visualize and compare leukocyte-endothelial interactions in three
      vascular beds within the same eye in mice. METHODS: Digital in vivo fluorescence
      microscopy was used to record a trans-corneal iris view, a superficial limbus
      view, and a trans-scleral anterior choroid view of mouse tissue. Uveitis was
      induced by intravitreal injection of E. coli endotoxin into BALB/c mice.
      Leukocytes were labeled systemically with SYTO-16 or rhodamine 6G. Leukocyte
      rolling and sticking were quantified at baseline and 4, 6, and 24 hours after
      endotoxin injection. RESULTS: In a normal animal, the limbus had 18 times the
      number of rolling leukocytes and 6 times the number of sticking leukocytes
      relative to the iris. All three vascular beds were affected by intravitreal
      injection of endotoxin. Although they each showed increased numbers of rolling
      and sticking cells, the levels and kinetics of these increases differed. Rolling
      peaked at 6 hours in the iris (34-fold increase from baseline) and limbus (7-fold
      increase) but was maximal in the choroid earlier with a 16-fold increase.
      Sticking was maximal at 4 hours for iris (96-fold increase) and choroid (19-fold
      increase) but peaked in the limbus at 6 hours (47-fold increase from baseline).
      CONCLUSIONS: This study demonstrates that leukocyte-endothelial dynamics are not
      the same in different vascular beds in the normal mouse eye. Furthermore, site
      specific differences in responses to intravitreally injected endotoxin, beyond
      what can be readily explained by differential distribution of endotoxin, were
      observed. The methodology can be used to test the hypothesis that endothelial
      cells within the eye have site-specific patterns of adhesion molecule expression.

PMID- 12221529
TI  - Human fetal retinal pigment epithelium induces apoptosis in human T-cell line
      Jurkat which is independent from its expression of TRAIL.
AB  - PURPOSE: To evaluate whether human fetal retinal pigment epithelial (HFRPE) cells
      express TRAIL (tumor necrosis factor related apoptosis inducing ligand). The role
      of TRAIL in HFRPE induced apoptosis was evaluated. METHODS: Pure cultures of
      HFRPE cells were isolated. The expression of TRAIL protein and mRNA in non
      activated and IFN-gamma activated HFRPE cells was evaluated with RT-PCR. The role
      of TRAIL in HFRPE induced apoptosis was assessed by incubating HFRPE cells with
      human T-cell leukemia line Jurkat (Jkt) in the presence or absence of
      neutralizing TRAIL antibodies. Cultures were pulsed with [(3)H]-thymidine to
      measure Jkt cell proliferation. The role of TRAIL was further examined by western
      blott evaluating the cleavage of caspases 8 and 10 in Jkt cells after their
      incubation with HFRPE cells. RESULTS: HFRPE cells expressed TRAIL mRNA. The
      expression of TRAIL mRNA and protein was up-regulated by IFN-gamma activation.
      However, anti-TRAIL antibodies were not able to prevent the HFRPE induced
      suppression of Jkt cell proliferation. The caspases 8 and 10 were also not
      cleaved in Jkt cells after their incubation with IFN-gamma activated HFRPE cells.
      CONCLUSIONS: Although HFRPE cells express TRAIL and its expression is upregulated
      by IFN-gamma activation, TRAIL is not involved in HFRPE induced apoptosis in Jkt
      cells. Currently the role of TRAIL in HFRPE cells is under investigation.

PMID- 12221531
TI  - Assessment of blood flow in orbital arteries in ocular sarcoidosis.
AB  - PURPOSE: Posterior uveitis in ocular sarcoidosis is characterized by obliterative
      arteriolitis, so-called "microangiopathy", in sarcoidosis that may affect blood
      flow in ocular arteries. This study was performed to evaluate blood flow velocity
      in orbital arteries in patients with ocular sarcoidosis. METHODS: This study is a
      case-control study. Thirty-two patients with posterior uveitis diagnosed on the
      basis of pathological or clinical findings as having ocular sarcoidosis
      functioned as cases and 24 healthy volunteers as controls. Pulse rate and blood
      flow velocities were measured in central retinal arteries, ophthalmic arteries,
      or short posterior ciliary arteries by the pulsed Doppler method. Laser
      flaremetry was also performed. Blood flow velocities were compared in patients
      with sarcoidosis and controls and the correlation coefficients between flare
      intensity values and flow velocities were evaluated using Student's t-test.
      RESULTS: Blood flow velocities in orbital arteries in eyes with sarcoidosis were
      significantly lower than those in normal eyes. The resistance index (RI) of
      peripheral vessels, which is calculated as (maximal velocity - minimal
      velocity)/maximal velocity, was significantly higher in patients with
      sarcoidosis. No association was found between flare intensity values and flow
      velocities. CONCLUSIONS: Patients with ocular sarcoidosis have impairment in
      ocular circulation. We speculate that changes in orbital blood flow resulted from
      inflammatory changes in fundus vasculature.

PMID- 12221532
TI  - Group IIA phospholipase A2 content of basal, nonstimulated and reflex tears.
AB  - PURPOSE: To determine the concentration of group IIA phospholipase A2
      (GIIAPLA(2)) in basal, nonstimulated and reflex tears of young normal subjects.
      METHODS: The GIIAPLA(2) content of tears was measured in left eye of 16 healthy
      subjects (mean age 24.5 +/- 2.2 years). Five samples were taken from each
      subject: nonstimulated sample; basal sample in a dark room after topical
      anesthesia; and reflex tear samples immediately on stimulation by bright light
      and breathing of the vapor of onions, and 1 and 3 minutes after the onset of tear
      flow. RESULTS: The GIIAPLA(2) content of reflex tears was statistically
      significantly lower than the GIIAPLA(2) content of basal tears, whereas there was
      no statistically significant difference in the GIIAPLA(2) content between
      nonstimulated and basal tears. CONCLUSIONS: The current results indicate that the
      basal and nonstimulated tears are similar in their GIIAPLA(2) content, and that
      the GIIAPLA( 2) content of tears decreases with stimulation, possibly due to
      dilution of GIIAPLA(2) content during reflectory hypersecretion of tears.

PMID- 12221533
TI  - Enhancement of rat tear IgA antibody responses following intranasal immunization
      with antigen and CpG ODN.
AB  - PURPOSE: To determine the effect of unmethylated oligodeoxynucleotides containing
      bacterial CpG motifs (CpG ODN) on the induction of rat tear IgA antibody
      responses. METHODS: Rats were immunized intranasally with either soluble
      dinitrophenylated bovine serum albumin (DNP-BSA) or poly(lactide-co-glycolide)
      (PLG) encapsulated DNP-BSA in combination with CpG ODN. The animals received two
      immunizations 21 days apart. Following the second immunization, tear, saliva and
      serum samples were collected for 28 days and analyzed for antigen specific
      antibodies. Tear IgA, saliva IgA and serum IgG antibody concentrations were
      determined by ELISA. RESULTS: Co-administration of CpG ODN with either soluble or
      encapsulated antigen resulted in significantly elevated levels of both tear and
      salivary IgA antibodies as well as levels of serum IgG antibodies.
      Microencapsulated DNP-BSA plus CpG ODN elicited higher levels of IgA antibodies
      in tears than did soluble antigen plus CpG ODN. CONCLUSIONS: CpG ODN is an
      effective mucosal immune modulator for enhancing rat tear IgA antibody responses
      to both soluble and microencapsulated antigens.

PMID- 12221534
TI  - A histological analysis of the protective effect of ischemic preconditioning in
      the rat retina.
AB  - PURPOSE: Ischemic preconditioning (IP) protects the retina from the damaging
      effect of subsequent ischemia in vivo. We aimed to investigate the histological
      alterations induced by the protective effect of IP to the retina. METHODS: The
      eyes of the rats were rendered ischemic by intra-ocular pressure (IOP) elevation.
      IP procedure consisted of producing ischemia for 5 minutes. Sham operation was
      similar to IP procedure except the pressure elevation. The operational eyes of
      sham and IP group underwent 60 minutes of ischemia 24 hours after the first
      procedure. The eyes contralateral to the experimental eyes made up the control
      group. The eyes were histologically analysed one week after the ischemia.
      RESULTS: The total retinal thickness of the sham group was significantly less
      than total retinal thickness of the control group (p < 0.001). There was not a
      significant difference between control and IP group regarding the total retinal
      thickness (p > 0.05). The thickness of the inner retinal layers of the sham group
      were significantly less than corresponding retinal layers of the control group (p
      < 0.001). The inner plexiform layer (IPL) and inner nuclear layer (INL) thickness
      values of the sham group were significantly less than same layers of the IP group
      (p < 0.001). Ganglion cell layer (GCL) thickness of the IP group was
      significantly less than GCL thickness of the control group (p < 0.001). IPL
      thickness of the IP group was significantly less than that of control group's (p
      < 0.05). The GCL and total retinal thickness of the IP group were significantly
      more than thickness of the corresponding layers of the sham group (p < 0.05).
      CONCLUSION: IP considerably protects inner retinal layers from subsequent
      ischemic damage in a high IOP ischemic model. This endogenous process could
      further be utilized to tailor specific neuroprotective strategies for retinal
      cells.

PMID- 12221535
TI  - Differential regulation of collagen degradation by rabbit keratocytes and
      polymorphonuclear leukocytes.
AB  - PURPOSE: Both activated keratocytes and infiltrated polymorphonuclear leukocytes
      (PMNs) contribute to corneal ulceration by degrading stromal collagen. The
      regulation of such collagen degradation by inflammatory cytokines was
      investigated with rabbit keratocytes and PMNs cultured in three-dimensional
      collagen gels. METHODS: Rabbit keratocytes or PMNs were cultured for 24 h in
      three-dimensional gels of type I collagen in the presence of plasminogen and
      various concentrations of either interleukin (IL)-1alpha, IL-6, IL-8, or tumor
      necrosis factor-alpha (TNF-alpha). Degradation of collagen during culture was
      assessed by measurement of released hydroxyproline. RESULTS: IL-1alpha increased
      the amount of collagen degraded by keratocytes or PMNs in a dose-dependent
      manner, whereas IL-6 had no effect on collagen degradation by either cell type.
      IL-8 increased the extent of collagen degradation by PMNs but not that by
      keratocytes, and TNF-alpha promoted collagen degradation by keratocytes but not
      that by PMNs. CONCLUSION: Inflammatory cytokines regulate collagen degradation by
      rabbit keratocytes and PMNs in culture in a differential manner, and therefore
      may contribute to the roles of these cells in corneal ulceration.

PMID- 12221536
TI  - [Amniotic membrane for ocular surface disease].

PMID- 12221537
TI  - [State-of-the-art in ocular malformations. Human and animal model studies].

PMID- 12221538
TI  - [AREDS and age-related macular degeneration].

PMID- 12221539
TI  - [Genetic and molecular characterization of 148 patients with autosomal dominant
      retinitis pigmentosa (ADRP)].
AB  - OBJECTIVE: Genetic characterization of a series of patients with autosomal
      dominant retinitis pigmentosa (ADRP). METHODS: All patients underwent complete
      ophthalmological examination including computerized perimetry,
      electroretinography and occasionally fluorescein angiography. Blood samples were
      drawn for genetic analysis of candidate genes namely rhodopsin (RHO), peripherin
      RDS, ROM-1, CRX, RP1 and NRL. RESULTS: 148 ADRP index cases were examined at our
      hospital from June 1991 to September 2001. Genetic analysis detected the
      following mutations: 29 different families (19.5%) carried a RHO mutation among
      which the Pro-347-Leu was the most frequent one, five different RP-1 mutations
      (3.3%), 2 RDS mutations and one NRL mutation, which is the second reported in the
      world literature. CONCLUSIONS: RHO followed by RP1 are the most frequent ADRP
      causing genes in our series as in other published ones, and RDS causes mainly
      macular dystrophies. Molecular characterization was possible in 37 families (25%)
      which is of great interest for visual prognosis and genetic counselling.

PMID- 12221540
TI  - [Analytic management in ophthalmology: towards a cost per hospital out- and in
      patient].
AB  - PURPOSE: To determine the total annual cost of the activities in the
      Ophthalmology Department at the Hospital La Mancha-Centro, Homogeneous functional
      group (HFG) of the INSALUD, and to estimate the cost per patient/process of both
      ambulatory patients and hospital in-patients. METHODS: The study was designed
      over 1 year period, from January to December 1997, and applied by using analytic
      accounting in 17,857 patients seen at the out-patient ophthalmology clinic and
      973 hospital in-patients who were classified by diagnosis-related groups (DRG)
      and sorted out by analysis of Case Mix index. RESULTS: We have determined the
      annual cost of our activity in both the ambulatory patient group and the hospital
      in-patient group classified by DRG and obtained the cost per process.
      CONCLUSIONS: To know systematically the annual cost of our medical and surgical
      activity is nowadays a necessary tool in the framework of the Total Quality Plan
      developed by the INSALUD's SIGNO Group since 1991. This leads us to the analytic
      management area and places us in the never ending search for the ideal model of
      cost per process determination.

PMID- 12221541
TI  - [Validation of a questionnaire for the diagnosis of dry eye].
AB  - PURPOSE: To develop and evaluate a questionnaire for diagnosis and follow-up of
      patients with symptoms suggestive of eye surface pathology. To evaluate the
      efficacy of dry eye treatment. METHODS: Samples were chosen among dry eye
      patients (n=44). A control group was chosen among the healthy population. The
      questionnaire was filled in at the beginning and end of the treatment with
      carbopol + polyvinyl alcohol (Siccafluid, Thea, Spain) four times a day. Initial
      and final punctuation was established and confronted with other classic
      diagnostic tests; fluorescein tear break up time, Schirmer test and Rose Bengal
      staining. RESULTS: Red eyes, lid inflammation, discharge, dry eye, sandy and
      foreign body sensations, burning, itching, discomfort, pricking, tearing and
      photophobia got significantly better after treatment (p<0.05). Lid reddening, lid
      inflammation, flakes in lashes, sticky eyes in the morning, teary eyes,
      transitory blurring vision and heavy sensation didn't improve (p>0.05). Total
      punctuation was significantly reduced at one month of treatment (p<0.01).
      Validation of the test was done against other standard tests (Schirmer test and
      Rose Bengal). We found a sensitivity of 76% and specificity of 71.5% for Schirmer
      test and a sensibility of 77% and specificity of 65% if gold standard was Rose
      Bengal. Predictive value (positive and negative), global value of the test and
      likelihood ratios were also assessed. CONCLUSION: This questionnaire is useful
      for diagnosis and follow-up of patients with dry eyes and other ocular surface
      symptoms. Carbopol + polyvinyl alcohol is useful for the treatment of patients
      with secretor tear insufficiency.

PMID- 12221543
TI  - [Exophthalmos secondary to a lateral rectus muscle metastasis].
AB  - CASE REPORT: 60-year-old male, with metastatic adenocarcinoma of the rectum
      sigmoid colon, who developed exophthalmos due to a tumour in the lateral rectus
      muscle, compatible with a diagnosis of metastasis. DISCUSSION: Metastasis in the
      extraocular muscles are very uncommon, but should form part of the differential
      diagnosis of any patient presenting exophthalmos, since although the majority of
      patients with such metastasis have a previously diagnosed malignant tumour, there
      are cases where they lead to the diagnosis of the primary tumour.

PMID- 12221542
TI  - [Subconjunctival mitomycin C for the treatment of ocular cicatricial pemphigoid].
AB  - PURPOSE: We study the efficacy of treating ocular cicatricial pemphigoid (OCP)
      with subconjuctival mitomycin C (MMC). METHODS: The patients were eligible for
      treatment under two criteria: 1. Significant complications of systemic
      immunosuppressant therapy. 2. Avanced stage of OCP. All patients received an
      injection of 0.25 ml of 0.2 mg/ml mitomycin C to both the upper and lower bulbar
      conjunctiva in both eyes. RESULTS: Four patients were treated with
      subconjunctival mitomycin C (both eyes) and were followed for an average of 17
      months (range 9-26 months). Three of four patients showed progression of the
      conjunctival disease and required concomitant systemic immunosuppressive therapy
      after subconjuctival mitomycin C. CONCLUSION: No complications of subconjunctival
      mitomycin C treatment were noted but, contrary to what other authors had
      referred, its use was not effective in preventing progression of conjunctival
      cicatrization in our patients with OCP.

PMID- 12221544
TI  - [Bilateral lagophthalmos in lepromatous leprosy. Case report].
AB  - CASE REPORT: A case of bilateral facial palsy with paralytic ectropion,
      lagophthalmos and corneal damage secondary to corneal exposure in a long-standing
      patient with lepromatous leprosy is presented. Correction of paralytic ectropion
      was performed by medial cantoplasty, tarsal strip and Medpor lower eyelid spacer
      implantation. Lagophthalmos was corrected by gold weight implant in the upper
      tarsus. DISCUSSION: Ocular findings in leprosy appear in 72% of patients. Facial
      nerve palsy occurs in 3-19.8%, being bilateral in 5%. In long standing cases with
      corneal complications secondary to exposure, surgical treatment is required.

PMID- 12221545
TI  - [Cytomegalovirus retinitis after highly active antiretroviral therapy: a case
      report].
AB  - CASE REPORT: An HIV infected patient with cytomegalovirus retinitis with a CD4
      lymphocyte count of 498 cells/mm3 after a good response to highly active
      antiretroviral therapy is described. COMMENT: Some aspects of the immune system
      after highly active antiretroviral therapy remain unknown. CD4 T lymphocyte count
      might not be a good marker to identify some patients at risk of developing
      cytomegalovirus retinitis after this therapy.

PMID- 12221546
TI  - [Extraction of subfoveal liquid perfluorocarbon].
AB  - PURPOSE/METHODS: Perfluorocarbon liquids (PFCL) are synthetic and transparent
      compounds with a high specific gravity which are very useful for vitreoretinal
      surgery. Subretinal injection of PFCL can occur during vitreoretinal surgery. A
      case report is presented of a patient with retained subretinal perfluoro-N-octane
      following retinal detachment repair for an ocular penetrating injury.
      RESULTS/CONCLUSION: Perfluoro-N-octane was retained in the subfoveal space for
      ten postoperative days and was removed thereafter. Based on our experience,
      residual PFCL droplets in the subretinal space for ten days after retinal
      detachment surgery allow a good anatomical and visual outcome, after two years
      follow-up.

PMID- 12221547
TI  - [Historical antecedents of ocular morphogenesis studies].

PMID- 12221548
TI  - [The wedjat eye].

PMID- 12221549
TI  - [Impact of multi-segmental aortic clamping and distal aortic perfusion on the
      prevention of postoperative paraplegia during thoracoabdominal aortic graft
      replacement].
AB  - OBJECTIVE: We present the impact of multisegmental aortic clamping under distal
      aortic perfusion and segmental artery reimplantation on the prevention of
      postoperative paraplegia during thoracoabdominal aortic graft replacement.
      PATIENTS: During the last 14 years in 47 patients (age range: 22 to 82 years;
      average: 57,9 +/- 13,2 years; 16 females and 31 males) with thoracoabdominal
      aortic aneurysm a graft replacement was performed with adjuncts of normothermic
      partial bypass and multisegmental aortic clamping. As many patent segmental
      arteries as possible were reimplanted. RESULTS: Five patients died during
      hospitalization, for an in-hospital mortality rate of 10,6 %. In the elective
      patients (n = 40), the hospital mortality rate was 7,5 %. The average number of
      segmental aortic clampings per patient was 2,83 +/- 1,19 times. In 39 patients
      (82,9 %), 117 segmental arteries were reimplanted or preserved by beveled
      anastomosis. Eighty-three out of 117 segmental arteries (70,9 %) were located
      between TH9 and L2. Postoperative paraplegia/paraparesis did not occur in any
      patient. CONCLUSION: In view of our results reimplantation of as many segmental
      arteries as possible under multisegmental aortic clamping with adequate distal
      aortic perfusion can be recommended for effective prevention of spinal cord
      ischemia in TAAA surgery.

PMID- 12221550
TI  - [Minimal incision abdominal aortic aneurysm repair].
AB  - OBJECTIVE: The use of a limited incision for abdominal aortic aneurysm (AAA)
      repair was evaluated, and its outcome was analyzed in comparison to standard open
      repair. PATIENTS AND METHODS: Between February 2000 and August 2001, 20 patients
      with an AAA underwent minimal incision repair (MINI) for tube graft implantation.
      The minimal skin incision was made after localization of aneurysm neck and aortic
      bifurcation by CT and DSA. For repair of the upper part of the AAA the abdominal
      incision was retracted toward the head of the patient who was in a jackknife
      decubitus position. Conversely, when the peripheral portion of the AAA was
      treated, the abdominal incision was retracted caudally with the patient in a flat
      or slightly bent decubitus position. The operation itself was performed using the
      standard conventional technique. The length of the abdominal incision was 10 cm.
      Clinical characteristics and in-hospital outcome of this procedure were compared
      to a group of patients who underwent repair of AAA by means of a standard open
      technique (OPEN). RESULTS: Patients age in the MINI and OPEN groups were similar
      (69 +/- 11 vs. 69 +/- 9 years). However, there were significant differences
      between the MINI and OPEN groups in the time for starting oral intake of food
      (2,4 +/- 1,2 vs. 7,4 +/- 5,5 postoperative days, p = 0,003), time for starting to
      walk outside the room (2,2 +/- 0,7 vs. 4,6 +/- 2,2 postoperative days, p = 0,01)
      and operation times (197 +/- 37 vs. 294 +/- 83 min, p = 0,0004). CONCLUSION:
      Minimal incision repair is technically feasible and combines the benefits of a
      minimal incision with those of conventional open repair, reducing patient
      recovery time.

PMID- 12221551
TI  - [Long-term results after endovascular treatment of peripheral arterial
      occlusions].
AB  - OBJECTIVE: Presentation of our long-term results with endovascular treatment of
      peripheral arterial occlusive disease. PATIENTS AND METHODS: We report on 115
      patients (98 male, 17 female), average 67 years, with 141 occlusions or stenoses
      in the iliac or femoral arteries that were treated by laser-angioplasty. RESULTS:
      Excellent primary results were obtained in 93 % of the stenoses and 74 % of the
      occlusions. The results depended on the length of the lesions. In femoro
      popliteal lesions < 10 cm length a success rate of 98 % could be observed, in
      lesions > 10 cm it was 71 %. The same was true for iliac lesions: the clinical
      success rate was 91 % in lesions < 5 cm as compared to 44 % in lesions > 5 cm.
      The long-term results were even satisfactory, the patency rate ranged to 85 % in
      stenoses and 75 % in occlusions, resp. CONCLUSION: Laser-angioplasty in our hands
      is an excellent treatment modality for occlusions/stenoses of the peripheral
      arteries and coronaries, a strong indication anticipated.

PMID- 12221552
TI  - [Long-term results after femoral vein valve repair for chronic venous
      insufficiency].
AB  - OBJECTIVE: Our long-term results with anterior venous sinus plication (AVSP) for
      femoral vein reconstruction will be presented. PATIENTS AND METHODS: Between 1986
      and 2001 we treated 2 100 patients in our hospital for chronic venous
      insufficiency. In 3.3 % of the patients (n = 70) an AVSP of the target valve,
      which is the highest valve of the femoral vein distally of the profundal vein
      branch was carried out. 50 patients could be followed for 2-15 (average 4.6)
      years postoperatively by phlebographic control. RESULTS: Four recovery patterns
      after valve repair were seen on venography. The most typical type was the
      plicated site stop seen in 22 of 50 patients (44 %). Here the venous reflux was
      stopped at the plicated site directly. The clinical results were good or
      excellent for all patients. No patient underwent a second procedure for
      recurrence of the symptoms. A profundal femoral vein reflux did not negatively
      influence patient outcome. CONCLUSION: AVSP is an excellent method of valve
      repair in strictly selected patients with chronic venous insufficiency (= no
      postthrombotic syndrome, no thrombotic occlusion of the femoral veins). Long-term
      results up to 15 years were highly satisfactory.

PMID- 12221553
TI  - [Results of standard varicose vein surgery].
AB  - The principles of modern varicose vein surgery are based on the interruption of
      the cranial and distal points of venous insufficiency. Especially due to the rise
      of alternate surgery procedures, we have scrutinized our results of varicose vein
      surgery. In a retrospective analysis, the results of those patients (pat.) who
      underwent venous surgery in our institution in 1995 were analysed. In 1995 we
      performed 1 575 varicose vein operations (n = 1 019 pat., 16.8 % male, 83.2 %
      female). 63.5 % were on an outpatient basis. During a follow-up period of 4 to 66
      months (av. 38 months) the patients were re-examined, 481 (47.2 %) by Duplex
      sonography, 94 (9.2 %) by clinical examination alone, from 103 (10.1 %)
      information was obtained through a written inquiry. 341 pat. (33.5 %) had just
      perioperative follow-ups. We didn't find any signs of varicosis in 301 pat. (33.3
      %). Minor side branches could be detected in 515 pat. (56.8 %). In 90 pat. (9.9
      %) a clearly visible varicosis could be seen. Based on the results of the Duplex
      examinations, 86 % of the pat. showed no recurrence after ligation of the sapheno
      femoral junction and stripping of the LSV, the results after stripping of the
      short saphenous vein were similar. Analysis of the inquiry forms concluded that
      62.3 % of the pat. were satisfied with surgery and the results. The results of
      the standard varicose vein surgery are satisfactory regarding recurrence rate and
      patient satisfaction. Our results are comparable to those published in
      prospective randomised studies. Alternate procedures, for example the CHIVA
      method, have still to proof their efficiency, especially in view of long-term
      results.

PMID- 12221554
TI  - [Perioperative antithrombotic prophylaxis in varicose vein surgery].
AB  - Antithrombotic regimens to prevent venous thromboembolism are standard in the
      treatment of in-and outpatients with thrombotic risk factors. A classification of
      the level of risk is made depending on the age, kind of operation, existing
      hereditary or acquired thrombophilic diatheses and concomitant disease. The
      antithrombotic prophylaxis is performed in accordance with the classification of
      risk level in low, moderate, high and highest risk levels. Varicose disease is a
      thrombotic risk factor. Varicose vein surgery may be classified as thrombogenic.
      Patients with varicose vein surgery and without other clinical risk factors are
      low-risk patients. In case of other acquired or hereditary risk factors
      antithrombotic prophylaxis in varicose vein surgery with low molecular weight
      heparin should be used. Compression elastic stockings are obligatory.

PMID- 12221555
TI  - [CT Venography and CT Angiography of the Pulmonary Arteries in Acute Pulmonary
      Embolism].
AB  - OBJECTIVES: To determine the diagnostic value of CT venography after CT
      angiography of the pulmonary arteries using multislice helical CT in the
      diagnosis of acute pulmonary embolism. METHODS: Between September 1999 and April
      2001 252 patients with clinically suspected pulmonary embolism were examined. CT
      angiography of the pulmonary arteries was followed by CT venography of the
      inferior vena cava, the iliac veins and the proximal femoral veins; after April
      2000 the popliteal veins and the proximal lower leg veins were additionally
      investigated. The examinations were performed with a double detector and a
      multidetector scanner (Elscint Twin and GE Lightspeed). RESULTS: Pulmonary
      embolism was found in 79/252 patients (40 central and 39 segmental/subsegmental
      PE). In 38/40 patients with central PE and in 22/39 patients with
      segmental/subsegmental PE in CT venography a deep venous thrombosis was detected,
      in 1/79 patient a doubled inferior vena cava could be found. In 5 patients with
      thrombosis of the inferior vena cava a transjugular cava filter placement was
      performed. In 13/173 patients without pulmonary embolism CT venography showed
      deep venous thrombosis. CONCLUSION: CT venography of the lower extremities is a
      practical and efficient additional examination to CT angiography in clinical
      suspected pulmonary embolism. It can detect the causing venous thrombosis with a
      high sensitivity.

PMID- 12221556
TI  - [Extraanatomic bypass surgery for peripheral arterial vascular disease--is it
      still justified?].
AB  - OBJECTIVE: Our results of extraanatomic bypass surgery in the last 5 years should
      be analysed in a retrospective study. PATIENTS AND METHODS: 66 extraanatomic
      reconstructions were performed in 65 patients (52 male, 13 female). Femoro
      femoral bypasses (78.8 %) were mainly included in this study, followed by axillo
      femoral (bifemoral) and obturator bypasses. The procedures could be divided in 45
      (68.2 %) primary and 21 (31.8 %) recurrent operations. 57.6 % of the patients
      revealed a critical lower limb ischemia. RESULTS: The bypass patency rates were
      97 % after one year and 81.1 % after 3 years. 24.2 % of the patients showed
      immediate postoperative complications, 12.1 % of them major complications
      (surgical and nonsurgical). No patient died postoperatively or in the first year
      after operation. The 3-year mortality rate ranged to 10.8 %. Major amputations
      had to be carried out in 4 patients (6.1 %) during the first year and in one
      patient later on, so that the total amputation rate amounted to 7.6 %.
      CONCLUSIONS: Our results prove extraanatomic reconstructions to be a valuable
      surgical tool in lower limb ischemia with good long-term success. Extraanatomic
      bypasses are technically simple procedures in the majority of cases and take good
      care of the patient with low morbidity and mortality.

PMID- 12221557
TI  - [Aortic reconstruction and resection of malignant tumors--one- or two-stage
      procedure?].
AB  - Surgical tactics in case of aortic aneurysms and simultaneously performed cancer
      resections are not uniform and still remain a matter of debate. From Jan. 1, 1995
      - Oct. 31, 2001 we operated on 37 patients suffering from aortic aneurysms (34
      infrarenal, 2 combined thoraco- abdominal, 1 thoracic aneurysm) and cancer (11
      esophageal, 6 gastric carcinomas, 3 small-bowel tumors, 5 large-bowel, and 12
      renal carcino-mas). None of the above mentioned patients presented with any graft
      infection, or other severe p. op. complications. According to these results, the
      one-stage operation of aortic aneurysms and cancer resection is feasible if
      appropriate care is given to patients selection, technical details and the rules
      of antisepsis, without affecting surgical morbidity and mortality.

PMID- 12221558
TI  - [Vulnerability of ileocoecal interposition pouch and colonic J-pouch to
      postoperative adjuvant radiotherapy].
AB  - AIM: The interposition of an ileocoecal segment has been introduced as an
      alternative procedure to impair the functional outcome following total mesorectal
      excision (TME). Up to now, there is no information concerning the effect of
      postoperative radiotherapy on the functional outcome of this method. PATIENTS AND
      METHODS: We compared functional outcome, anorectal physiology, and radiation
      therapy-related morbidity of 18 patients treated with TME und ileocoecal
      interposition (ICI) of which ten had postoperative radiotherapy, with 15 patients
      who had TME and colonic J-pouch (CJP) reconstruction of which 7 were subjected to
      radiotherapy. RESULTS: Patients with no radiotherapy revealed a satisfying
      functional result with a similar median frequency of defecation of 4.25 (2-5) and
      3 (2-6) and an incontinence-score of 2.8 (0-6) and 1.0 (0-2) after ICI and CJP,
      respectively. Median stool frequency (7 (2-11) (ICI) and 5 (2.5-11) (CJP)) and
      incontinence score (6 (0-12) (ICI) and 7 (6-12) (CJP)) were markedly increased in
      both groups after radiotherapy. Besides a reduced anal resting pressure, a lower
      compliance and a smaller volume of the neorectum were observed in the irradiated
      patients. A radiogenic injury which required surgery was seen in 4/10 patients
      after ICI. In three of these four patients the interposed ileocoecal segment was
      mainly affected. None of the patients treated with a CJP suffered a similar
      complication. DISCUSSION: These data indicate that postoperative radiotherapy
      severely impairs the functional outcome after TME independent of the type of
      surgery used for reconstruction, and causes a significant morbidity after ICI.
      CONCLUSION: Postoperative radiotherapy following TME should be indicated
      cautiously, and ICI should not be used if postoperative radiotherapy is intended.

PMID- 12221559
TI  - [Total mesorectal excison and colonic-J-pouch-anal anastomosis in the therapy of
      low rectal carcinoma--results in 116 patients].
AB  - BACKGROUND: Total mesorectal excision with coloanal anastomosis has been accepted
      as standard therapy of low rectal carcinoma. Interposition of colonic J-pouch
      improved the functional results and was associated with better postoperative
      quality of life. In this study our own results are evaluated. METHODS: Between 1.
      7. 1999 and 30. 6. 2001 116 patients underwent total mesorectal excision with
      coloanal anastomosis and colonic J-pouch interposition. Thirty-eight patients
      (32.9 %) with uT3-carcinoma received preoperative adjuvant short-time irradiation
      with 5 x 5 Gy and seven patients (6.0 %) with local non resectable cancer
      conventional radiochemotherapy with 50.4 Gy. A protective stoma was constructed
      in 56 patients (48.3 %). Six patients (5.2 %) received secondary stoma due to
      anastomotic complications. RESULTS: A clinically relevant insufficiency of the
      anastomosis occurred in eight patients (6.9 %). Three patients needed a secondary
      laparotomy for local peritonitis. Fecal diversion was constructed secondarily in
      four patients due to pouchvaginal fistula and in one patient for ischiorectal
      abscess one year after the first operation. Six patients revealed small fistulas
      in the radiological examination without clinical consequences. Five patients with
      primary fecal diversion showed pouchvaginal fistulas. The over-all anastomotic
      complication rate was 16.4 %. The follow-up demonstrated already in the first
      year after surgery good functional results with satisfying anorectal continence.
      Only nine patients complained of intermittent incontinence for solid stool. No
      patient needed a definitive stoma due to anastomotic complications. One patient
      developed a small anastomotic tumor recurrence one year after surgery. He could
      be cured by abdomino-perineal excision. CONCLUSIONS: Our results confirm the
      importance of total mesorectal excision as standard therapy for low rectal
      carcinoma. Good functional results can be obtained already in the early
      postoperative period by colonic J-pouch interposition.

PMID- 12221560
TI  - [The Transverse Coloplasty Pouch (TCP)--function and subjective judgement in
      comparison with the surgically more complicated J-Pouch].
AB  - The present study shows the comparison of function and subjective judgement
      between two pouch-constructions after TME as treatment for rectal cancer. In 61
      cases we constructed a J-Pouch, in 25 cases a transverse coloplasty pouch (TCP).
      The sex distribution was nearly the same. The influence of additional treatment
      like neoadjuvant radiotherapy or adjuvant chemo-radiatio was considered. Patients
      were asked about stool frequency, -consistency, continence, quality of life etc.
      9 patients were not alive at follow up. 54 patients (70 %) could be interviewed
      and examined. 6 months after operation patients with a J-Pouch had a daily stool
      frequency of 4 times versus 6 times with a TCP. 19 % of patients with a J-Pouch
      suffered from incontinence problems compared to 33 % with a TCP. Obstipation was
      only a problem after J-Pouch-construction (12 %). The question on a "good"
      quality of life was positively answered by 56 % of patients in the J-pouch-group
      versus 39 % in the TCP-group. 17 % after J-pouch-construction versus 6 % after
      TCP-construction judged the quality of life as "bad". The results of this study
      show the TCP being a good alternative pouch-construction instead of the
      surgically more complicated J-pouch after TME.

PMID- 12221561
TI  - [Results of emergency ERCP in the treatment of acute biliary pancreatitis].
AB  - Indication for emergency ERCP (< 48 hours after onset of symptoms) with stone
      extraction from the common bile duct (CBD) in patients with biliary pancreatitis
      remains controversial. In our hospital emergency ERCP with stone extraction from
      CBD is part of the therapeutical concept in patients with biliary pancreatitis.
      The aim of the study was to elucidate retrospectively results and impact of this
      concept on morbidity and lethality in surgical intensive care patients. We
      included all patients with a documented indication for emergency ERCP. Among 4
      466 patients (1. 1. 1999-31. 12. 2000) treated in the SICU, 37 (0.9 %) required
      an emergency ERCP due to a biliary pancreatitis. (26 females/11 males, 62.0 +/-
      15.4 years). After ERCP stones were present in 32 of the 37 patients with
      subsequent successful endoscopic extraction in all cases but one. The mean
      duration from admission to ERCP was 11.6 +/- 10.1 hours. Bilirubin as well as
      amylase and lipase decreased after ERCP (p < 0.05). Only in one case an elevation
      of pancreatic enzymes over the pre-ERCP values was observed, an aggravation of
      pancreatitis was not seen in our series. In 5 of the 37 cases bile duct stones
      were not found after ERCP despite strong clinical suggestion (elevation of
      bilirubin and pancreatic enzymes, ultrasound). During the observational period 2
      patients died, in one case possibly due to the ERCP. Emergency ERCP removed in
      our series the pancreatitis causing agent. Still considering the limitations of a
      retrospective study these positive results are stimulating us to continue with
      our therapeutical concept.

PMID- 12221562
TI  - [Primary malignant tumor of the aorta].
AB  - A 63-year old man suffering from bilateral leg pain was admitted to our hospital
      with an occlusion of the infrarenal abdominal aorta. A bifurcated dacron graft
      was implanted and a histological examination of the thrombotic material was
      performed. Atypical cells were detected in the thrombus leading to an
      investigation of the thoracic aorta showing an unclear mass in the aortic arch.
      The tumor was resected and the aorta replaced with a dacron graft. Histology
      revealed a primary sarcoma. The patient is doing well 6 months after operation.

PMID- 12221563
TI  - [The day after elections is the first day of the next campaign, and the day after
      reforms is the start of the next debate for reform].

PMID- 12221564
TI  - [The current value of percutaneous transhepatic biliary drainage].
AB  - Percutaneous transhepatic biliary drainage (PTBD) is a well established method in
      the treatment of obstructive jaundice. Major indications are malignant diseases.
      PTBD may be necessary preoperatively in cases with severe jaundice or cholangitis
      or as part of palliative treatment concepts. In the past, it has been proposed
      that a period of preoperative PTBD may improve the morbidity rates of surgery.
      Various studies could not prove this theory. The significance of preoperative
      PTBD has changed, as observed during a 15 years period in our own institution,
      the indications for preoperative PTBD have decreased by half. At present, the
      majority of treatments with PTBD are palliative (almost 70 % of all procedures).
      The diagnostic opportunities of the transhepatic approach (intraductal
      sonography, cholangioscopy, biopsy) are exploited only in few selected cases.
      Since the radiological approach ist considered to be invasive and related to
      serious complications most patients are being referred to endoscopic drainage
      first. Radiologists are consulted in complicated cases of jaundice and when
      endoscopic approaches have failed. The retrospective evaluation of more than 1000
      procedures over a period of 16 years demonstrates good results with a low rate of
      serious complications. During the two observed periods of nine and seven years,
      respectively, there occurred complications like sepsis in 1.9 %/0.5 %,
      peritonitis in 0.5 %/0.7 %, severe bleeding in 0.5 %/1.5 %, procedure-related
      death in 0.8 %/0.7 %. The overall rate of serious complications was 5 %/3.4 %.
      These results are comparable to those of the endoscopic approach with a
      complication rate of 3.6-14 % and a mortality rate of 0.5 %.

PMID- 12221565
TI  - [The value of multi-slice computed tomography for early diagnosis of focal
      cerebral ischemia].
AB  - The aim of this survey is the characterization of the present value of multi
      slice computed tomography (MSCT) for the assessment of hyperacute cerebral
      ischemia based on our experience and a review of the literature. MSCT is compared
      with single-slice CT (SSCT) as to the diagnostic value of standard cranial CT, CT
      angiography (CTA) and perfusion CT. CTA obtained with MSCT surpasses CTA obtained
      with SSCT. For perfusion CT, the value added by MSCT is small. With regard to
      standard cranial CT, MSCT and SSCT are considered equivalent. CTA and perfusion
      CT should be used in patients with acute stroke if the indication for
      thrombolysis is entertained but diffusion and perfusion weighted MRI cannot be
      carried out. This applies to both SSCT and MSCT. If advanced MRI and advanced CT
      are available, MRI continues to be the preferred imaging modality.

PMID- 12221566
TI  - Esophageal foreign bodies: removal of the new euro coins with a magnet tube.
AB  - AIM OF THIS STUDY: We use a magnet tube to extract esophageal coins. It is
      smaller than the Foley balloon catheter and easier to handle than a forceps. We
      present the magnet tube maneuver and investigate whether the new euro coins can
      be removed with a magnet. METHOD: We take radiographs of coins and measure the
      adhesive force of the magnet and compare with the 10 Pfennig German coin which we
      most often removed successfully from the esophagus. RESULTS: The 1, 2, and 5 euro
      cent pieces are magnetic and can possibly be removed with a magnet tube. The non
      magnetic pieces can be identified based on the rim and size. DISCUSSION: When an
      esophageal foreign body is not round and smooth like a coin, the fluoroscopic
      guided procedure becomes more risky with respect to mucosal injury. When a large
      object is stuck in the esophagus for more than 24 hours, an endoscopy must be
      considered to rule out any severe damage to the esophageal wall.

PMID- 12221568
TI  - [Imaging diagnosis of solitary pulmonary nodules on an open low-field MRI system-
      comparison of two MR sequences with spiral CT].
AB  - OBJECTIVE: To evaluate and compare two fast gradient-echo sequences (GRE)
      concerning the visualization of solitary pulmonary nodules with an open low-field
      MRI system in comparison to computed tomography. MATERIALS AND METHODS: Fourteen
      patients with solitary pulmonary nodules detected by spiral CT ranging in size
      from 6 mm to 42 mm (mean 20 mm) underwent MRI on an open 0.2 T scanner using a
      spoiled 2D GRE (2D FLASH; TR/ TE/Flip = 100 ms/7.5 ms/30 degrees ) and a totally
      refocused 2D steady-state GRE (True-FISP; TR/TE/FA = 7.3 ms/3.5 ms/80 degrees ).
      The image quality concerning artifacts (by flow, breathing and susceptibility)
      and the morphologic characteristics of the nodules were scored and compared with
      CT by two independent radiologists. The diameters of the nodules measured by MRI
      were compared with CT measurements. The sequences were also evaluated with regard
      to the signal-to-noise ratio (SNR) of the lesion. RESULTS: All lesions were
      detected with the 2D FLASH sequence. True-FISP failed to find a granuloma with a
      size of 6 mm. The 2D FLASH was rated significantly superior to true FISP
      concerning image quality artifacts by susceptibility as well as concerning to CT
      the presentation of nodule characteristics. In MR images, the size of lesions was
      significantly smaller than in CT images for both sequences: for 2D FLASH the mean
      difference was 0.9 mm and for true FISP 2.6 mm. The SNR of the nodules was
      significantly higher for the 2D FLASH than for the true FISP. CONCLUSION: In low
      field MRI, the 2D FLASH sequence is superior to the 2D true FISP sequence in
      imaging of pulmonary nodules. With the 2D FLASH sequence nodules of 6 mm or
      larger in size can be visualized.

PMID- 12221567
TI  - [Value of contrast-enhanced ultrasound vs. CT and MRI in palpable enlarged lymph
      nodes of the head and neck].
AB  - PURPOSE: To compare the value of B-mode-, plain and contrast enhanced color
      Doppler ultrasound, CT and MRI with respect to their diagnostic accuracy in
      palpable enlarged cervical lymph nodes. MATERIAL AND METHODS: Thirty patients (18
      - 90 years old) with palpable enlarged lymph nodes of the head and neck underwent
      B-mode-ultrasound, plain and contrast enhanced color Doppler, CT and MRI (gold
      standard: histologic analysis in 22 and clinical follow up for at least six
      months in eight patients). The criteria of malignancy were maximal and minimal
      lymph node diameter, M/Q-ratio, various morphologic criteria (necrosis, hilus
      line, internal structure, contour, contrast enhancement), spectral Doppler
      indices, and vascular architecture in color Doppler. RESULTS: The highest
      sensitivity (= 1.00, specificity = 0.07 - 0.15) was obtained measuring the lymph
      node diameter independent on the used imaging modality (ultrasound, CT, MRI), the
      highest specificity (= 1.00, sensitivity = 0.71) analyzing the vascularity of the
      lymph node by plain color Doppler. The highest diagnostic (= 0.93) accuracy was
      delivered by contrast enhanced color Doppler analysis of the vascularity.
      Sensitivity (= 0.94) and specificity (= 0.92) of this imaging modality were only
      slightly inferior to the top values. Fisher's exact test revealed significant
      values in differentiating malignant from benign lymph nodes for B-mode- and MR
      analysis of the M/Q-ratio (p < 0001/p < 0.05), B-mode morphology (p < 0.00005),
      plain and contrast enhanced color Doppler analysis of the vascularity (p <
      0.0001/p < 0.000005), MR-morphology (p < 0.0001), and CT-morphology (p < 0.005).
      CONCLUSION: CT is inferior to MRI, B-mode-ultrasound and contrast-enhanced color
      Doppler in the differential diagnosis of selectively analyzed, palpably enlarged
      cervical lymph nodes using the criteria of our study. The analysis of the MR
      morphology revealed a slightly inferior diagnostic accuracy to B-mode morphology
      and color Doppler analysis of the vascularity.

PMID- 12221569
TI  - [Invasive pulmonary aspergillosis--CT findings in context with the clinical
      course].
AB  - PURPOSE: To investigate the impact of chest radiographs and CT in patients
      suffering from invasive pulmonary aspergillosis (IPA) compared to the clinical
      course. PATIENTS AND METHODS: Twenty-three patients with confirmed diagnosis of
      IPA between January 1996 and September 1999 were included in this study. Signs of
      inflammatory infiltrates on chest radiographs and CT were retrospectively
      evaluated in relation to the onset of the clinical symptoms. Infiltrates on CT
      were analyzed in detail with respect to number, morphology, and localization.
      RESULTS: Seventy-six infiltrates were found on the CT of 22 patients; one patient
      had diffuse areas of lung infiltrates. Both lungs were affected by infiltrates in
      14 patients. Pleural effusions were confirmed in 12 patients. Twelve patients had
      typically round foci with halo and nine patients crescent air signs. The
      preferred localization of lung infiltrates was segment 6. The median interval
      between the onset of clinical symptoms and the first radiographic changes was 5.5
      days, with an additional interval of 4.5 days until confirmation by CT.
      Localization, number of infiltrates, and clinical course were not related.
      CONCLUSION: In immune-compromised patients with fever, a CT of the chest should
      be carried out as soon as possible to detect signs indicative of IPA.
      Morphological changes on CT like a round focus with halo and crescent air sign
      support the diagnosis of IPA. In this context, special attention should be
      directed to pulmonary segment 6.

PMID- 12221570
TI  - [Preoperative wire localisation of breast lesions by tissue harmonic imaging
      (THI) sonography].
AB  - PURPOSE: To obtain a fast and reliable preoperative wire localisation of occult
      lesions in dense breast tissue by tissue harmonic imaging (THI) sonography when
      localisation by mammography is not reliable enough. MATERIAL AND METHODS: In
      addition to biplane mammography for breast screening or for follow-up examination
      after breast-saving therapy, ultrasound was performed by two independent
      radiologists in 350 patients with mastopathic or fibrotic breast tissue. Using a
      multifrequency probe (5 - 10 MHz), lesions were documented by conventional B-mode
      and by THI in similar projections. In 25 lesions not precisely identified in
      mammography sonographically guided puncture with wire localisation was performed.
      RESULTS: In 22 of 350 patients 25 circumscribed suspicious lesions with an
      average diameter of 8 mm were identified, regarded suspicious by ultrasound but
      not by mammography. Nineteen of 25 lesions found by M-Mode and THI, an additional
      6 only by THI. Guided puncture and wire localisation was achieved in 10 minutes
      on the average. In B-mode, the course of needle and wire was reliably seen in 16
      of 25 cases, in THI in all cases. After surgical removal of tissue,
      histopathology revealed a ductal or lobular carcinoma in 19 cases, metastasis in
      three cases and benign complicated cysts with fibrotic tissue in the remaining
      three cases. CONCLUSION: THI is superior to B-mode ultrasound in differentiating
      suspicious lesions in dense glandular breast tissue. If tumor signs in
      mammography are not reliable enough or if a precise localisation is not possible,
      sonographically guided puncture by THI can give reliable results and,
      furthermore, is faster and more comfortable for the patient than localisation by
      mammography.

PMID- 12221571
TI  - [Comparison of wire versus carbon localization of non-palpable breast lesions].
AB  - PURPOSE: To compare the accuracy of wire and carbon localization in
      stereotactically localized open breast biopsy. PATIENTS AND METHODS: From June
      1995 to December 1997, a total of 725 stereotactic wire or carbon dye
      localizations were performed in 698 female patients. Success of localization was
      evaluated either by a malignant histopathological diagnosis or by mammographic
      follow-up. A lesion was considered to be missed if it could be still seen on
      follow-up mammography. RESULTS: In 703 of 725 cases, the success of localization
      could be evaluated with 427 (61 %) lesions localized with a wire and 276 (39 %)
      with carbon. Seven (1 %) out of 703 lesions were missed at open biopsy. Three
      lesions of these had been localized with wire and three lesions with carbon. The
      miss rates were 0.9 % and 1.1 %, respectively (p = 1.0). CONCLUSION: Both wire
      and carbon localization are reliable and accurate in the localization of non
      palpable breast lesions. Concerning efficiency and costs, carbon dye seems to
      offer a promising compromise.

PMID- 12221572
TI  - [Analysis of vascularity in breast tumors--comparison of high frequency
      ultrasound and contrast-enhanced color harmonic imaging].
AB  - PURPOSE: To compare the ability of standard power Doppler and color harmonic
      imaging for visualising breast tumor vascularity using ultrasound probes of
      various frequencies, and to evaluate the influence on diagnostic accuracy using
      ultrasound contrast agent. MATERIALS AND METHODS: Twenty patients (x = 43.6 +/-
      11.7 years) with suspected malignancy of the breast underwent power Doppler to
      evaluate vascularity and to offer a differential diagnosis of the lesion. Two
      criteria were used for differential diagnosis: The quantitative extent of
      vascularity ("percentage vessel area", PVA) and the qualitative assessment of
      vascular architecture. The following power Doppler modes were compared in every
      patient: Plain and enhanced (Levovist(R)) 9 MHz and 12 MHz standard power mode
      and enhanced 9 MHz color harmonic imaging-(CHI). RESULTS: The PVA increased from
      a mean of 2.2 +/- 2.9 % (9 MHz standard plain) via 4.8 +/- 4.1 % (12 MHz standard
      plain), 9.7 +/- 15.3 % (9 MHz standard enhanced), 17.4 +/- 20.0 % (9 MHz CHI
      enhanced) up to 19.4 +/- 14.8 % (12 MHz standard enhanced). The perceptibility of
      the vascular structure was best using the enhanced 12 MHz standard power mode,
      immediately followed by the enhanced 9 MHz CHI mode. The improved detection of
      vascular signal did not translate into improved diagnostic accuracy. The highest
      diagnostic accuracy (95 %) was obtained using the enhanced 9 MHz CHI mode
      (criterion "PVA") and the enhanced 9 MHz standard power mode (criterion "vascular
      structure"), whereas the 12 MHz probes delivered insufficient diagnostic accuracy
      and very low specificity. CONCLUSION: Best quantitative and qualitative
      visualisation of the tumor vascularity was achieved using the enhanced 12 MHz
      standard power mode. Nevertheless, the highest diagnostic accuracy was obtained
      using enhanced 9 MHz standard power Doppler and enhanced 9 MHz color harmonic
      imaging. The visualisation of tumor vascularity and, partially, the diagnostic
      accuracy are improved significantly by color harmonic imaging without changing
      the probe frequently.

PMID- 12221573
TI  - [Percutaneous core-needle biopsy of palpable breast tumors. Do we need ultrasound
      guidance?].
AB  - INTRODUCTION: Percutaneous core-needle biopsy is widely accepted for preoperative
      histologic assessment of suspicious breast lesions. The purpose of this study was
      to asses the impact of continuous sonographic guidance on diagnostic accuracy of
      large core needle biopsy of palpable breast lesions. METHOD: We analysed 170
      breast lesions in a retrospective study. Percutaneous breast biopsies were
      performed by using a biopsy gun with 14-gauge needles. Eighty-eight biopsies were
      performed under continuous ultrasound guidance (group II) and 82 biopsies without
      ultrasound documentation of the procedure (group I). Core needle diagnoses were
      compared with the patients final tissue diagnosis as based on surgical excisional
      biopsy. RESULTS: In patient group I, 17 lesions were categorized as core breast
      biopsy cancer misses (sensitivity 79 %). The sensitivity in this group showed an
      obvious dependency on tumor size. Among the 17 false negative lesions, 13 lesions
      were 3 cm in mean diameter or smaller. Two false negative findings occurred in
      group II (sensitivity 98 %), with a tumor size of 0.5 and 1.0 cm. CONCLUSION:
      Sonographic guidance is indispensable to ensure adequate diagnostic accuracy for
      core-needle biopsy of palpable breast lesions.

PMID- 12221574
TI  - [Interindividual-variability of the analysis of regional myocardial wall function
      after myocardial infarction and revascularization].
AB  - PURPOSE: The gold standard for diagnosis myocardial viability is the functional
      recovery after revascularization. Aim of the study was to compare (1) qualitative
      analysis and (2) quantitative wall thickening by cine MRI and (3) circumferential
      shortening by tagged MRI the analysis of regional wall function of an infarcted
      area before and after revascularization. MATERIAL AND METHODS: Ten patients (age
      60 +/- 11 years) with infarct-associated regional left ventricular wall motion
      abnormalities were examined by cine and tagged MRI on average two weeks after the
      myocardial infarction and re-examined three months after revascularization. Eight
      healthy volunteers served as a control for tagged MRI. Interobserver
      variabilities of two observers were calculated using the kappa-statistics for
      grading of wall motion abnormalities as well as for detection of functional
      recovery by qualitative analysis, measurement of wall thickening of cine MRI, and
      measurement of circumferential shortening by tagged MRI, respectively. RESULTS:
      Grading of wall motion abnormalities revealed interobserver-variabilities of the
      study and control group of kappa = 0.8 and kappa = 0.84, kappa = 0.02 and kappa =
      0.5, and kappa = 0.1 and kappa = 0.17 for qualitative analysis, wall thickening
      analysis and measurement of circumferential shortening, respectively. The
      interobserver-variability for the definition of wall motion recovery was kappa =
      0.8 for all three methods. CONCLUSION: Qualitative analysis of wall motion
      abnormalities has the lowest interobserver-variability for the grading of wall
      motion abnormalities. The interobserver-variabilities of qualitative and
      quantitative analysis are comparable for the diagnosis of regional wall motion
      recovery. Thus, qualitative analysis of cine MRI can be used for grading regional
      wall motion in clinical studies.

PMID- 12221575
TI  - [Secretin-stimulated MR cholangiopancreatography (MRCP): visualization of the
      normal pancreatic duct in comparison with ERCP].
AB  - PURPOSE: To determine whether the application of secretin improves the depiction
      of the normal pancreatic duct and to document the time course of any possible
      improved visualisation. PATIENTS AND METHODS: Twenty-eight patients with a normal
      pancreatic ductal system, proved by ERCP, were prospectively enrolled in our
      study. MRCP was carried out in a 1.0 Tesla unit using a thick slab single-shot
      turbo-echo sequence (TR: infinity, TE: 1100 ms, FA: 150 degrees, slab thickness:
      65 mm). Following acquisition of a non-enhanced image, 1 clinical unit/kg
      bodyweight of secretin was injected intravenously. During the subsequent ten
      minutes the MR measurement was repeated every 30 seconds. The images were
      independently evaluated by two investigators. RESULTS: The improvement in quality
      after administration of secretin was statistically significant for both
      investigators (p < 0.05), but no significant difference was found between both
      investigators concerning the quality of the images (p = 0.49). Prior to the
      secretin application, the entire ductal system only be evaluated in ten cases
      (35.7 %) by both investigators, afterwards in 26 cases (92.9 %). Improvement was
      achieved after a mean time of 1.5 minutes and lasted until the ninth minute.
      CONCLUSION: Intravenous application of secretin improves image quality of MRCP
      also in patients with no pancreatic pathology. Improvement begins after 1.5
      minutes and lasts for about seven minutes.

PMID- 12221576
TI  - [Radiological assessment of small bowel obstructions: Value of conventional
      enteroclysis and dynamic MR-enteroclysis].
AB  - PURPOSE: To compare small bowel lesions, especially stenoses, with conventional
      enteroclysis, static MRI and dynamic MR-enteroclysis. MATERIALS AND METHODS:
      Forty-two patients with Crohn's disease or other suspected small bowel lesions
      were examined. MRI was performed in a static and a dynamic way either within one
      hour after conventional enteroclysis (n = 30) or a few days afterwards (n = 12).
      In order to monitor bowel filling and to characterize stenoses in a dynamic
      fashion, 4 series of coronal T2w HASTE breath hold sequences were used, first
      without additional bowel opacification and then during administration of 1,5 l
      methyl cellulose via a naso-intestinal tube in the MR unit. Intravenously applied
      Buscopan was used to reduce bowel movement. RESULTS: In 4 out of 42 Patients,
      application of methylcellulose was limited to 1000 ml because of gastrointestinal
      complaints or visible gastral reflux. All patients could be evaluated. Static MRI
      performed within one hour after conventional enteroclysis and no additional bowel
      opacification showed insufficient bowel distension. Distension was still better
      than in MRI without prior application of contrast medium. On the contrary,
      dynamic MR - enteroclysis lead to controlled and complete bowel distension which
      allowed for significantly better evaluation of normal bowel anatomy and
      pathological alterations of the gut. Because of a better bowel distension and
      dynamic evaluation, MR-enteroclysis revealed significantly more stenoses (n = 42)
      than MRI obtained with less distension (n = 27, p < 0.001), and characterization
      of lesions was comparable to conventional enteroclysis (p < 0.001). Fixed and non
      fixed stenoses could be differentiated by dynamic MR-enteroclysis. Furthermore,
      extraluminal complication of Crohn's disease such as abscesses and fistulae or
      large bowel manifestation of disease were shown in 13 patients. CONCLUSIONS:
      Dynamic MR-enteroclysis is feasible in routine diagnostic work-up of the small
      bowel. It is superior in depicting intra- and extraluminal manifestation of small
      bowel lesions and enables characterization of stenoses comparable to conventional
      enteroclysis.

PMID- 12221577
TI  - [CT-angiography of the carotid artery: First results with a novel 16-slice-spiral
      CT scanner].
AB  - PURPOSE: To evaluate a novel multislice CT system (16-slice-spiral-CT scanner)
      for the diagnosis of carotid artery stenosis. MATERIAL AND METHODS: Five patients
      with symptomatic atherosclerotic disease of the carotid arteries were examined
      with a 16- slice-spiral-CT scanner. Collimation was 16 x 0.75 mm, table speed 36
      mm/s (pitch of 1.5), rotation time 0.5 s, tube current was 160 eff.mAs at 120 kV.
      60 ml of contrast material were injected with a power injector followed by a
      saline flush. The start delay was measured with test bolus method (20 ml CM).
      Interactive multiplanar reformation (iMPR) and thin slab MIP as well as volume
      rendering were used for image evaluation and presentation. RESULTS: Scan time was
      9 s for a range of 300 mm. This allowed imaging the whole length of the carotid
      artery (aortic arch to circle of Willis) in a true arterial phase. Pulsation
      artefacts did not impair the evaluation of the vessels at the level of the aortic
      arch. Overall image quality of both "source images" and 3D-reconstructions was
      excellent, due to a reduced voxel size of 0.03 mm (3). Image evaluation and
      postprocessing (iMPR, MIP) was done within 15 min. iMPR was highly accurate for
      demonstrating plaque morphology and determining the percentage of the stenosis.
      CONCLUSION: For the first time, true arterial phase images of the entire carotid
      artery with high spatial resolution could be acquired using a 16-slice-spiral-CT
      scanner. This method offers the potential to replace catheter angiography in the
      evaluation of carotid artery stenosis.

PMID- 12221578
TI  - [Time-resolved MR angiography of the renal artery: morphology and perfusion].
AB  - PURPOSE: To prove the hypothesis that renal artery stenosis and changes in renal
      perfusion can be detected with contrast-enhanced time-resolved MR angiography in
      a single examination. MATERIAL AND METHODS: In 71 patients, 137 renal arteries
      and 14 accessory renal arteries were studied. The examinations were performed on
      a 1.5 T system. A T 1 -weighted gradient echo sequence with a temporal resolution
      of 7 s was used. Single dose of contrast material (0.1 mmol/kg Gd-DTPA) was
      injected with a power injector with a flow rate of 2 ml/s. Criterion for the
      assessment of renal perfusion was the slope ratio of the signal intensity time
      curve in both kidneys. RESULTS: Forty renal artery stenoses and one occlusion of
      a renal artery were detected. In 48 kidneys (35 %) segmental arteries were
      evaluated. The accuracy of the slope ratio (limit value 0.75) concerning the
      detection of unilateral renal artery stenosis was 92.6 % (sensitivity 75 %,
      specificity 95.7 %). CONCLUSION: Time-resolved MR angiography can detect changes
      in renal perfusion in patients with unilateral renal artery stenosis.

PMID- 12221579
TI  - [Merkel cell carcinoma of the calf: MRI imaging of a rare tumor].

PMID- 12221580
TI  - [Recurrent renal artery stenosis--endovascular brachytherapy with a rhenium 188
      filled balloon catheter].

PMID- 12221581
TI  - [Penicilliosis infection: differential diagnosis of non-Hodgkin lymphoma in a
      patient with HIV infection].

PMID- 12221584
TI  - Pseudolaric acid analogs as a new class of peroxisome proliferator-activated
      receptor agonists.
AB  - Extracts of the root and trunk barks of the Chinese tree Pseudolarix kaempferi,
      which contain pseudolaric acids, are used in Chinese medicine for treatment of
      fungal infections. Pseudolaric acid B (PLAB) is the major constituent that
      exhibits anti-fungal activity. The nuclear peroxisome proliferator-activator
      receptors (PPAR) were proposed as a cellular target for the action of PLAB and
      its analogs. PLAB and two derivatives were tested for the activation of PPAR
      isoforms in two mammalian cell lines. CV-1 and H4IIEC3 cells were transfected
      with phorbol ester response element or PPAR response element reporter constructs,
      and CV-1 cells were co-transfected with the individual PPAR isoform expression
      plasmids. PLAB showed similar concentration-dependent effects for the activation
      of PPAR alpha, gamma and delta isoforms in CV-1 and H4IIEC3 cells. O
      Deacetylation of PLAB (PLAC) or esterification of the free carboxy group of PLAB
      with beta-D-O-glucopyranoside (PLAG) markedly reduced or abolished the activation
      of these PPAR isoforms. In H4IIEC3 cells, PLAB increased the activation of
      endogenous PPARalpha and the phospholipase C signaling pathway; and stimulated
      peroxisomal fatty acyl-CoA oxidase activity. These effects of PLAB on the
      activation of endogenous PPARalpha and phospholipase C-dependent pathway were
      blocked by staurosporine. These results suggest that the action of PLAB on
      PPARalpha in H4IIEC3 cells is mediated by a protein kinase C dependent
      phosphorylation. Based upon these findings, the chemical class of biologically
      active diterpene acids related to PLAB may have promise for the treatment of
      metabolic and pathophysiological disorders that are regulated by these nuclear
      receptor isoforms.

PMID- 12221585
TI  - In vitro activity of hederacolchisid A1 compared with other saponins from Hedera
      colchica against proliferation of human carcinoma and melanoma cells.
AB  - Hederacolchisid A1, a new oleanolic acid monodesmoside, isolated from Hedera
      colchica K. Koch, an ivy species endemic in Georgia, was evaluated in vitro for
      antiproliferative activity on cancer cells versus normal cells in comparison to
      cisplatin. Investigations were made on six human cell lines (colon adenocarcinoma
      DLD-1, ovarian teratocarcinoma PA 1, lung carcinoma A 549, breast adenocarcinoma
      MCF7, prostatic adenocarcinoma PC 3 and malignant melanoma M4 Beu) versus normal
      human fibroblasts, by assaying both cellular metabolic activity (RTT test) and
      DNA content in living cells (test with Hoechst 33,342) after 48 h continuous
      contact. Results demonstrated the strong cytotoxicity of hederacolchisid A 1 on
      all cancer cells (IC50 from 4.5 to 12 microM). The antiproliferative effects on
      malignant melanoma M4 Beu (IC50 ca 4.5 microM) versus normal cells (IC50 ca 7.5
      microM) suggests that, despite a lack of specificity for cancer cells,
      hederacolchisid A1 has potential anti-tumor applications. Comparison of the
      cytotoxicity of hederacolchisid A 1 with that of five other saponins from H.
      colchica, offers some new information about structure-activity relationships. It
      was observed that i) for a same sugar sequence, monodesmosides with oleanolic
      acid as aglycone exhibit higher cytotoxicity than those containing hederagenin,
      ii) the sugar sequence O-alpha-L-rhamnopyranosyl (1 --> 2)-alpha-L
      arabinopyranoside at C3 induces strong cytotoxicity and might be identified as a
      basic sequence for anti-tumor activity of oleanolic acid monodesmosides. iii) a
      complementary glucopyranosyl moiety branched at C1 of arabinose increases the
      cytotoxicity against malignant melanoma M4 Beu, prostatic adenocarcinoma PC 3 and
      normal fibroblasts in a different manner for each type of monodesmoside. A slight
      increase whose amplitude was quite similar on cancers and normal cells, was
      observed with oleanolic acid monodesmoside. This increase was much higher with
      hederagenin monodesmoside and markedly elevated in normal cells than in cancer
      cells.

PMID- 12221586
TI  - Physiological responses to a natural antioxidant flavonoid mixture, silymarin, in
      BALB/c mice: I induction of transforming growth factor beta1 and c-myc in liver
      with marginal effects on other genes.
AB  - Silymarin, a mixture of flavonolignans isolated from Silybum marianum, is known
      for its hepatoprotective properties. We investigated the expression of cytokines
      in mouse liver following treatment with 0, 10, 50, and 250 mg/kg of silymarin
      once daily for 5 days. A dose-related but insignificant decrease of circulating
      alanine aminotransferase and aspartate aminotransferase after silymarin treatment
      was observed, suggesting that silymarin treatment did not induce hepatic damage.
      Silymarin treatment caused significant increases in the expressions of
      transforming growth factor (TGF) beta1 and c-myc in liver. No significant
      difference was detected among these treatments in the expression of hepatocyte
      growth factor, interferon gamma, tumor necrosis factor alpha, and class II major
      histocompatibility complex. These results suggest that alterations of TGFbeta1
      and c-myc expression in the liver may be involved in the hepatoprotective effects
      of silymarin observed in other studies.

PMID- 12221587
TI  - Structural effects on the bioactivity of dehydroabietic acid derivatives.
AB  - The synthesis and the evaluation of the antimicrobial activity against a
      filamentous fungus, yeasts and bacteria of 15 hydrophenanthrene compounds derived
      from dehydroabietic acid, bearing different functional groups and different
      stereochemistry of the A/B ring junction are disclosed. The results obtained
      showed how their activity is dependent of the functionality at C-18, which can be
      increased by deisopropylation or introduction of other groups into the molecule.
      While the filamentous fungus tested is sensitive to almost all of the compounds
      under study, the aldehyde function showed to be of major importance to the
      inhibition of yeast. Alcohols and aldehyde C-18 derivatives also inhibit the
      growth of a Gram-positive bacteria, whereas Gram-negative are not sensitive.

PMID- 12221588
TI  - Inhibition of inducible nitric oxide synthesis by catalposide from Catalpa ovata.
AB  - Catalposide (1) and two related iridoids were isolated from the stem of Catalpa
      ovata (Bignoniaceae) by bioassay guided fractionation. Catalposide (1)
      significantly inhibited the production of nitric oxide (NO) in lipopolysaccharide
      (LPS)-stimulated RAW 264.7 macrophages in a dose-dependent manner. RT-PCR and
      Western blot analyses demonstrated that catalposide (1) suppressed the expression
      of inducible nitric oxide synthase (iNOS) gene and iNOS protein. Catalposide (1)
      also inhibited the activation of LPS-induced NF-kappaB as analyzed by
      electrophoretic mobility shift assay (EMSA). In addition to the inhibitory effect
      on NO production in LPS-stimulated RAW 264.7 cells, catalposide (1) significantly
      inhibited the NO production in cytokine-stimulated human DLD-1 and rat vascular
      smooth muscle (VSM) cells in a dose-dependent manner.

PMID- 12221589
TI  - Potentiation of vasoconstrictor response and inhibition of endothelium-dependent
      vasorelaxation by gallic acid in rat aorta.
AB  - In the isolated rat thoracic aorta, gallic acid potentiated the vasoconstrictor
      response to phenylephrine. The potentiation produced by gallic acid was absent in
      endothelium-denuded arteries. The potentiation was abolished by N(G)-nitro-L
      arginine methyl ester, an inhibitor of nitric oxide synthesis, and slightly
      attenuated by an addition of L-arginine, while indomethacin or BQ610 had no
      effect. The potentiation of response to phenylephrine was not found for
      structural modifications of gallic acid, except for caffeic acid. Gallic acid
      also inhibited vasorelaxation induced by acetylcholine, sodium nitroprusside or
      prostacyclin, especially that by acetylcholine. The effect on vasorelaxation
      induced by acetylcholine was decreased by esterification of the carboxy group of
      gallic acid, and in the absence or by the methylation of the o-dihydroxy group.
      Caffeic acid inhibited the vasorelaxation, though the effect was smaller than
      that of gallic acid. These findings indicate that gallic acid produces a
      potentiation of contractile response and inhibition of vasorelaxant responses,
      probably through inactivation of nitric oxide (NO), in which endothelially
      produced NO is principally involved, and that the modification of functional
      groups of the gallic acid molecule abolishes the potentiation of contractile
      response and attenuates the inhibition of vasorelaxant responses.

PMID- 12221590
TI  - Involvement of nitric oxide in the mediation of the hypotensive action of the
      essential oil of Mentha x villosa in normotensive conscious rats.
AB  - Recently, we showed that intravenous (i.v.) treatment with the essential oil of
      Mentha x villosa (EOMV) in pentobarbitone-anaesthetised rats decreased blood
      pressure; the effect occurred independently of the presence of an operational
      central autonomic drive to the cardiovascular system. This finding suggested that
      the hypotensive activity of EOMV may result from its vasodilatory effects
      directly upon vascular smooth muscle. The present study examines this possibility
      and whether EOMV-induced hypotension is mediated, at least in part, by an
      endothelial L-arginine/nitric oxide pathway. In conscious rats, i.v. injections
      of bolus doses (1 to 20 mg/kg) of EOMV elicited immediate and dose-dependent
      decreases in mean aortic pressure (MAP) and heart rate (HR). Pretreatment with
      i.v. hexamethonium (30 mg/kg) reduced the EOMV-induced bradycardia without
      affecting the hypotension. However, i.v. pretreatment with the nitric oxide
      synthase inhibitor, N(G)-nitro-L-arginine methyl (L-NAME, 20 mg/kg), reduced
      partially, but significantly, the maximal percent decreases in MAP elicited by
      EOMV without affecting the bradycardia. In rat isolated thoracic aorta
      preparations, EOMV (1 - 130 microg/ml) induced a concentration-dependent
      reduction of potassium (60 mM)-induced contraction. This smooth muscle-relaxant
      activity of EOMV was significantly reduced by the incubation of endothelium
      intact rings with L-NAME (20 microM), as evidenced by the significant enhancement
      in the IC50 for EOMV-induced reduction of potassium-induced contraction (133.8 +/
      26.5 vs. 65.2 +/- 8.2 microg/ml in the absence of L-NAME). Furthermore, the
      vasorelaxant effects of EOMV in endothelium-denuded aortic rings were also
      significantly reduced (IC50 = 109 +/- 10 microg/ml), compared to those observed
      in segments with intact endothelium (IC50 = 61 +/- 13 microg/ml). These results
      show that i.v. treatment with EOMV dose-dependently decreases blood pressure in
      conscious rats, and that this action is due to an active vascular relaxation
      rather than withdrawal of sympathetic tone. Released nitric oxide from vascular
      endothelial cells appears partially involved in the aortic relaxation induced by
      EOMV and in turn in the mediation of EOMV-induced hypotension. They further
      support the concept that EOMV-induced hypotension and bradycardia occurred
      independently.

PMID- 12221591
TI  - Muscarinic agonist properties involved in the hypotensive and vasorelaxant
      responses of rotundifolone in rats.
AB  - The acute cardiovascular effects of rotundifolone (ROT), the major constituent
      (63.5 %) of the essential oil of Mentha x villosa (OEMV), were tested in rats by
      using a combined (in vivo and in vitro) approach. ROT (1, 5, 10, 20 and 30 mg kg(
      1) i. v.) induced a significant and dose-dependent hypotension and bradycardia in
      non-anaesthetized normotensive rats. The hypotensive effect was significantly
      attenuated by pre-treatment of the rats with atropine (2 mg kg(-1) i. v.) or L
      NAME (20 mg kg(-1) i. v.). Furthermore, the bradycardic effect was abolished by
      atropine. In isolated rat atrial preparations, ROT (10, 100, 300 and 500 microg
      ml(-1)) produced concentration-related negative inotropic and chronotropic
      effects. In isolated intact aortic rings, increasing concentractions of ROT (0.3,
      1, 10, 100, 300 and 500 microg ml(-1)) were able to antagonize the contractile
      effect of phenylephrine (1 microM) (IC50 = 184 +/- 6 microg ml(-1)). The smooth
      muscle-relaxant activity of ROT was inhibited by either removal of vascular
      endothelium, atropine (1 microM), L-NAME (100 and 300 microM) or indomethacin (10
      microM) (IC50 values = 235 +/- 7, 247 +/- 8, 387 +/- 21, 723 +/- 75 and 573 +/-
      38 microg ml(-1), respectively). These results suggest that rotundifolone
      markedly lowers arterial pressure and heart rate in non-anaesthetized animals.
      The hypotensive action of rotundifolone can be a consequence of a decrease in
      heart rate and peripheral vascular resistance, probably due to a non-selective
      muscarinic receptor stimulation.

PMID- 12221592
TI  - The cardioprotection of rutaecarpine is mediated by endogenous calcitonin related
      gene peptide through activation of vanilloid receptors in guinea-pig hearts.
AB  - Previous investigations have shown that calcitonin gene-related peptide (CGRP)
      protects against myocardial ischemia-reperfusion injury and that rutaecarpine
      activates vanilloid receptors to evoke CGRP release. In the present study, we
      examined whether rutaecarpine enhances preservation with cardioplegia in guinea
      pig hearts, and whether the protective effects of rutaecarpine are related to
      stimulation of endogenous CGRP release via activating vanilloid receptors. The
      isolated guinea-pig heart was arrested using St. Thomas Hospital solution, and
      then reperfused with normothermic Krebs-Henseleit solution for 30 min after a 4-h
      hypothermic ischemic period. Hypothermic ischemia caused a decline in cardiac
      function (left ventricular pressure, +/-dp/dt(max), heart rate and coronary flow)
      and an increased release of creatine kinase during reperfusion. Rutaecarpine at
      the concentration of 1.0 microM significantly improved the recovery of cardiac
      function and reduced the release of creatine kinase during reperfusion after
      hypothermic ischemia. Rutaecarpine at the concentration of 3.0 microM
      significantly reduced the release of creatine kinase and increased the coronary
      flow, but only caused a slight improvement of left ventricular pressure, +/
      dp/dt(max), heart rate during reperfusion. The cardioprotective effects of
      rutaecarpine were abolished by capsazepine, a competitive vanilloid receptor
      antagonist, or by CGRP (8-37), a selective CGRP receptor antagonist. Rutaecarpine
      at the concentration of 1.0 or 3.0 microM significantly increased the release of
      CGRP, which was also abolished by capsazepine. These results suggest that
      rutaecarpine enhances preservation with cardioplegia in guinea-pig hearts and
      that the protective effects of rutaecarpine are due to stimulation of endogenous
      CGRP release via activating vanilloid receptors.

PMID- 12221593
TI  - Protective effects of demethylbellidifolin on myocardial ischemia-reperfusion
      injury in rats.
AB  - The effect of demethylbellidifolin (DMB), a major compound of Swertia davidi
      Franch, on ischemia-reperfusion injury was studied in rats. Ischemia-reperfusion
      injury in vivo and in vitro was induced by 20 min of global ischemia followed 40
      min of reperfusion and 60 min of coronary artery occlusion followed 180 min of
      reperfusion, respectively. DMB (100 or 300 microg/L) significantly improved the
      recovery of cardiac function during reperfusion in isolated rat hearts, as shown
      by enhancement of coronary flow, left ventricular pressure and its first
      derivatives (+/-dp/dt(max)). DMB decreased the release of creatine kinase in
      coronary effluent as well as the level of malondialdehyde in myocardial tissues.
      In vivo, DMB (0.5 or 1.0 mg/kg) markedly decreased infarct size and the release
      of creatine kinase. These results suggest that DMB protects the myocardium
      against damage due to ischemia-reperfusion in rats. The present study also
      suggests that the effect of DMB may be related to inhibition of lipid
      peroxidation.

PMID- 12221594
TI  - Evaluation of salicin as an antipyretic prodrug that does not cause gastric
      injury.
AB  - Pharmacokinetic and pharmacological studies were performed to compare the
      antipyretic effects of salicin (SL), saligenin (SG, an aglycone of SL) and
      salicylic acid (SA, an active metabolite of SL) in rats. When SL was administered
      orally to rats, SA appeared slowly in the plasma and levels increased gradually,
      in contrast to the rapid appearance observed after oral administration of sodium
      salicylate (SANa) or SG. Orally administered SL did not affect the rectal
      temperatures of afebrile rats at a dose of 5 mmol/kg; at this dose, SANa and SG
      lowered body temperature significantly. However, it significantly reduced yeast
      induced fever, producing a normal body temperature, and completely prevented
      fever when administered simultaneously with yeast. SL did not induce gastric
      lesions even at a dose of 5 mmol/kg; conversely, SANa and SG induced severe
      gastric lesions in a dose-dependent manner at 1, 2.5 and 5 mmol/kg. Poor
      absorption of SL and rapid absorption of SA and SG were confirmed in an in vivo
      system, as well as in an in vitro system using everted rat jejunal sacs. Only
      small amounts of SA and SG were detected in the intestinal tracts of rats 1 h
      after oral administration, whereas more than 50 % of an SL dose was recovered as
      SL and SG from the intestinal tracts 1 h after treatment and 15.8 % of the dose
      was still present as SG 4 h after administration. When given to germ-free rats,
      19.8 % of the SL dose was recovered intact, mainly from the cecum, and no SG was
      detected even at 4 h after treatment. These results indicate that SL is a prodrug
      which is gradually transported to the lower part of the intestine, hydrolyzed to
      SG by intestinal bacteria, and converted to SA after absorption. It thus produces
      an antipyretic action without causing gastric injury.

PMID- 12221595
TI  - Saccopetrins A and B, two novel gamma-lactones from Saccopetalum prolificum.
AB  - Two new gamma-lactones, saccopetrin A (1) and saccopetrin B (2), together with 10
      known compounds have been isolated from the roots of Saccopetalum prolificum.
      Their structures were established by spectroscopic and chemical methods. The
      absolute configuration of 1 was determined by chemical transformation and the
      Mosher method. Cytotoxic activities were evaluated against several different cell
      lines. Compound 2 exhibited stronger cytotoxic activities than 1 against KB and
      HCT-8 cell lines at a concentration of 10(-5) mol/L.

PMID- 12221596
TI  - New alloaromadendrane, cadinene and cyclocopacamphane type sesquiterpene
      derivatives and bibenzyls from Dendrobium nobile.
AB  - Five new sesquiterpene glycosides with alloaromadendrane, cadinene and
      cyclocopacamphane type aglycones, one new cyclocopacamphane type sesquiterpene,
      two new bibenzyls and eight known compounds have been obtained from stems of
      Dendrobium nobile Lindl. Their structures were determined on the basis of 1D, 2D
      NMR and HR-MS analyses and chemical methods.

PMID- 12221597
TI  - Bioactive constituents of the seeds of Brucea javanica.
AB  - A new quassinoid, yadanziolide S (1), was isolated from the seeds of the
      traditional Chinese medicinal herb, Brucea javanica, along with ten known
      compounds, flazin, bruceine D, yadanziolide B, bruceoside A, yadanziolide S,
      yadanzigan, glycerol 1,3-bisoleate, azelaic acid, (+/-)-8-hydroxyhexadecanoic
      acid, and vanillin. Compound 1 is the first quassinoid to have been isolated from
      B. javanica without a methyleneoxy bridge between C-8 and C-13, and its structure
      was determined using spectroscopic methods, and confirmed by single-crystal X-ray
      diffraction. All isolates were evaluated for their potential to induce human
      promyelocytic leukemia (HL-60) cell differentiation, and to inhibit
      cyclooxygenase-1 (COX-1), -2 (COX-2), and 7,12-dimethylbenz[a]anthracene (DMBA)
      induced lesions in a mouse mammary organ culture model.

PMID- 12221598
TI  - Multi-component metabolic classification of commercial feverfew preparations via
      high-field 1H-NMR spectroscopy and chemometrics.
AB  - There is increasing interest in evaluating the clinical efficacy of herbal
      medicines. However, there are significant analytical problems associated with
      quality control and the measurement of the overall composition of such complex,
      multi-component mixtures as normally required in the pharmaceutical industry.
      Here we describe a novel NMR spectroscopic and pattern recognition analytical
      approach to investigate composition and variability of a commonly used herbal
      medicine. 600 MHz (1)H-NMR spectroscopy and principal components analysis (PCA)
      was used to discriminate between batches of 14 commercially available feverfew
      samples based on multi-component metabolite profiles. Two of the batches were
      significantly different from the other twelve. The twelve remaining classes could
      be classified into discrete groups by PCA on the basis of minor differences in
      overall chemical composition. NMR based pattern recognition (PR) analysis of
      extracts proved to be superior to PR analysis of HPLC traces of the same
      mixtures. This work indicates the potential value of NMR combined with PCA for
      the characterisation of complex natural product mixtures, and the discrimination
      of samples containing allegedly identical ingredients.

PMID- 12221599
TI  - In vitro inhibition of 1,3-beta-glucan synthase by glycolipids from
      convolvulaceous species.
AB  - Sixteen convolvulaceous glycolipids selected from the tricolorin (1 - 7) and
      orizabin (8 - 16) series, proved to be strong in vitro inhibitors of the enzyme
      that catalyzes the synthesis of 1,3-beta-D-glucan, a major polymer of fungal cell
      walls. Results provide an insight into function of the specific structures of
      these complex macrocyclic lactones as inhibitors of the 1,3-beta-D-glucan
      synthase and open the possibility of using these compounds as starting points for
      the development of antifungal agents that act by inhibiting fungal cell-wall
      synthesis.

PMID- 12221600
TI  - Aromatase inhibitory activities of standishinal and the diterpenoids from the
      bark of Thuja standishii.
AB  - The absolute stereostructure of a novel skeletal diterpene, standishinal (1),
      from the bark of Thuja standishii was confirmed by X-ray crystallographic
      analyses of 1 and its p-bromobenzoate derivative. Aromatase inhibitory activities
      of standishinal, eight known diterpenes, totarol, 12-methoxyabieta-8,11,13-trien
      11-ol, 12-hydroxy-6,7-seco-abieta-8,11,13-triene-6,7-dial, trans-communic acid,
      labda-8(17),13-dien-12 R,15-olid-19-oic acid, 12 S-hydroxylabda-8(17),13(16),14
      trien-19-oic acid, 13-oxo-15,16-dinorlabda-8(17),11 E-dien-19-oic acid and 14-oxo
      15-norlabda-8 (17),12 E-dien-19-oic acid from the plant, and four synthetic
      analogs were evaluated using a recombinant human aromatase. Among them,
      standishinal and its diacetate derivative had significant inhibitory activities.

PMID- 12221601
TI  - Cytotoxic sesquiterpene lactones from Carpesium abrotanoides.
AB  - Eight sesquiterpene lactones, 4 alpha,5 alpha-epoxy-10 alpha,14-dihydro
      inuviscolide (1), 2,3-dihydroaromomaticin (2), carpesiolin (3), carabrone (4),
      carabrol (5), telekin (6), ivalin (7) and 11,13-didehydroivaxillin (8), were
      isolated from the aerial parts of Carpesium abrotanoides Linne (Compositae). In
      vitro cytotoxicity testing was carried out against L1210, A549, SK-OV-3, SK-MEL
      2, XF-498 and HCT-15 tumor cell lines. Sesquiterpene lactone compounds 1 - 8
      showed significant cytotoxic activity (ED50 values, < 20 microM) against all
      tumor call lines tested. Among these compounds, 4 alpha,5 alpha-epoxy-10 alpha,14
      dihydro-inuviscolide (1), 2,3-dihydroaromomaticin (2), telekin (6) and ivalin (7)
      showed cytotoxic activity (ED50, < 10 microM) comparable to that of cisplatin.

PMID- 12221602
TI  - Sesquiterpenes with hepatoprotective activity from Cnidium monnieri on tacrine
      induced cytotoxicity in Hep G2 cells.
AB  - Bioassay-guided fractionation of the EtOH extract of Cnidium monnieri (Apiaceae)
      furnished two hepatoprotective sesquiterpenes, torilin (1) and torilolone (2),
      together with a new derivative, 1-hydroxytorilin (3). Compounds 1 and 2 showed
      hepatoprotective effects on tacrine-induced cytotoxicity in human liver-derived
      Hep G2 cells. The EC50 values of compounds 1 and 2 were 20.6 +/- 1.86 (P < 0.01)
      and 3.6 +/- 0.1 (P < 0.01) microM, respectively. Silybin as a positive control
      showed an EC50 value of 69.0 +/- 3.4 microM.

PMID- 12221603
TI  - Anti-trypanosomal activity of helenalin and some structurally related
      sesquiterpene lactones.
AB  - The anti-trypanosomal activity of six sesquiterpene lactones (helenalin,
      mexicanin I, 11alpha,13-dihydrohelenalin acetate, chamissonolide, ivalin and
      isoalantolactone) against the African Trypanosoma brucei rhodesiense and American
      T. cruzi was investigated. All tested compounds were found active towards both
      parasites, the former being generally more sensitive. Helenalin was the most
      active compound in the series with IC50 values of 0.051 and 0.695 microM against
      T. brucei rhodesiense and T. cruzi, respectively. The low IC50 value for T. b.
      rhodesiense indicates that helenalin type compounds may be interesting candidates
      for further evaluation.

PMID- 12221604
TI  - Intracellular calcium involved in the long-term potentiation induced by
      securinine in dentate gyrus of anesthetized rats.
AB  - The effect of nimodipine on securinine-induced long-term potentiation in rat
      hippocampus was studied. The rise of intracellular calcium during the induction
      of long-term potentiation was measured using Fura-2/AM--a Ca (2+) fluorescent
      chelator. Results showed that intracerebroventricular injection of nimodipine (4
      nmol) blocked the induction of long-term potentiation elicited by securinine (0.4
      pmol) and high-frequency stimulation (p < 0.05), but 2-amino-5-phosphonovaleric
      acid (5 nmol) had no inhibitory effect on securinine-induced long-term
      potentiation. In addition, securinine-induced intracellular calcium increment was
      inhibited by nimodipine (10(-6) mol. L(-1), p < 0.01), but not by 2-amino-5
      phosphonovaleric acid (10(-6) mol. L(-1), p > 0.05).

PMID- 12221605
TI  - Effects of ferulic acid on the impairment of inhibitory avoidance performance in
      rats.
AB  - Ferulic acid (50 and 100 mg/kg) reversed the step-through latency shortened by
      scopolamine and cycloheximide but not by p-chloroamphetamine in an inhibitory
      avoidance performance. Piracetam and tacrine might reverse the step-through
      latency shortened by the above drugs. However, ferulic acid, piracetam or tacrine
      alone at any used dose did not influence motor activity produced by non-shock
      rats. Furthermore, the cerebral blood flow of rats treated with ferulic acid,
      piracetam or tacrine was enhanced. From these results, we suggest that the
      potency of ferulic acid was better than that of piracetam, but its action
      mechanism was somewhat different from that of piracetam and tacrine. Thus, the
      attenuating effects of ferulic acid on the avoidance performance impairment were
      related to memory processes, and might be enhancing the cholinergic activities
      and cerebral blood circle.

PMID- 12221606
TI  - Variation in content of taxol and related taxanes in Eastern Himalayan
      populations of Taxus wallichiana.
AB  - Extraction and analysis of paclitaxel and other taxanes in bark, needle leaves
      and stem segments of male and female plants of Taxus wallichiana, representing
      several populations, indicate that significant variation in taxane content exists
      within the population. Bark accumulated maximum amount of paclitaxel in almost
      all plants. Populations located at higher altitude tended to accumulate more
      paclitaxel than lower altitude plants. Seasons in which samples were collected
      and plant age have also been shown to affect paclitaxel accumulation. No effects
      of plant sex on paclitaxel content of the plants analyzed were observed.
      Significant differences in baccatin-III and 10-deacetylbaccatin III content were
      found to exist in the trees analyzed in this study.

PMID- 12221607
TI  - Features of development of Stevia rebaudiana shoots cultivated in the roller
      bioreactor and their production of steviol glycosides.
AB  - Growth and development of Stevia rebaudiana shoots cultivated in the roller
      bioreactor and their production of steviol glycosides (SGs) were investigated. It
      was found that, owing to the highly favorable conditions of shoot cultivation
      created in such an apparatus, the intensity of shoot growth and SG production
      appeared to be 1.5 - 2.0 times higher than those of the shoots grown in tubes.
      These results indicate the existence of a positive correlation between these two
      processes. The data obtained suggest that the enhanced SG production is due to
      the differentiation of chlorenchyma cells and formation of specific subcellular
      structures for the glycoside to be accumulated.

PMID- 12221608
TI  - Chemical constituents and antimicrobial activity of the essential oil of Lantana
      xenica.
AB  - The aim of this work was to evaluate the chemical composition of Lantana xenica
      essential oil and its antimicrobial activity. The oil from the aerial parts of
      Lantana xenica Mold. (Verbenacea) was obtained by steam distillation and analyzed
      by gas chromatography/mass spectrometry. The major constituent of the oil was (E)
      caryophyllene (35.2 %), with minor amounts of gamma-cadinene (13.3 %), alpha
      pinene (9.3 %), ocimene (9.2 %) and germacrene D (6.6 %). The antimicrobial
      assays showed that the essential oil of L. xenica inhibited the growth of
      Bacillus cereus and Proteus mirabilis and both bacteria were inhibited by (E)
      caryophyllene, the major component of the oil. Enterococcus faecalis,
      Staphylococcus epidermidis and S. aureus showed a lower inhibition. The bacteria
      Micrococcus luteus, Klebsiella sp., Escherichia coli and the yeast Candida
      albicans were insensitive to both the oil and (E)-caryophyllene.

PMID- 12221609
TI  - Abietane diterpenoids from callus cultures of Taxus baccata.
AB  - A new compound was isolated from calli of Taxus baccata L. and assigned the
      structure 3beta,11-dihydroxy-12-methoxyabieta-8,11,13-triene-7-one. Two other
      metabolites were identified as 3-oxocryptojaponol and taxamairein C, both
      previously isolated from Taxus mairei.

PMID- 12221610
TI  - [Guidelines for the sociomedical assessment of performance in patients suffering
      from coronary heart disease (CHD)].
AB  - The following guidelines were developed for the medical assessment services of
      the German Federal Insurance Institute for Salaried Employees (BfA). Starting
      from day-to-day practice criteria and attributes to guide decisions for a
      systemisation of the sociomedical assessment of performance in coronary heart
      disease (CHD) were compiled. The guidelines aim at standardising the sociomedical
      assessment of performance and help to make the decision-making process more
      transparent - e.g. for the assessment of applications for decreased earning
      capacity benefits. The guidelines summarise typical manifestations of CHD and
      describe the necessary medical information for the sociomedical assessment of
      performance. Relevant assessment criteria for the medical history, clinical
      examination and for diagnostic tests - especially of myocardial functioning - are
      illustrated. The assessment of the individual's capacity is outlined, taking
      occupational factors into account. Following the determination of dysfunctions
      the remaining abilities and disabilities, respectively, are deduced and compared
      with occupational demands. Finally inferences are drawn regarding the
      occupational capacity of the individual.

PMID- 12221611
TI  - [E-health and Cyberdoc - "health portals" from a professional and quality
      assurance viewpoint].
AB  - As a special expression of e-business in the health service the sphere of e
      health has developed in recent years which increasingly manifests itself in the
      internet via health portals. Next to the transmitting of medical contents, the
      offer of community functions and the trading with goods from the medical sector,
      these health portals now increasingly provide advisory services for citizens by
      medical experts. Even if these services are predominantly effected by physicians,
      this activity is in agreement with the regulations of the currently valid
      professional responsibility law for German physicians, as its main emphasis (at
      the moment) is on health prevention and information. The safeguarding of quality
      of the online retrievable health information creates a further problem. The
      different approaches to the safeguarding of the quality of medical contents in
      the internet do not exempt the user from making a self-responsible decision as to
      which information he may consider reliable. This is due to the fact that there
      are no standardised control criteria.

PMID- 12221612
TI  - [What Turkish-speaking women expect in a German hospital and how satisfied they
      are with health care during their stay in a gynaecological hospital in Berlin - a
      comparative approach].
AB  - Although cultural diversity in German metropolises is rapidly increasing,
      immigrant patients are rarely included in clinical studies. Specific needs of
      these patients are hardly known. In a comparative study, 320 German and 262
      Turkish immigrant women, respectively, were interviewed via bilingual
      questionnaires to assess their expectations from and their satisfaction with
      provided health care services. While no significant differences could be found
      between basic expectations concerning anticipated health care standards between
      the two study groups, women of Turkish origin were markedly less satisfied with
      provided health care services. High expectations of immigrant patients towards
      information during their stay, communication with doctors and nurses and
      psychosocial services were only insufficiently met. The results indicate that
      specific health-relevant factors, such as social and educational status,
      knowledge of German language and health knowledge together with structural
      deficiencies of a health care service that is not prepared to correspond properly
      to patients of different social and cultural backgrounds, have a negative impact
      on patient satisfaction for migrant women.

PMID- 12221613
TI  - ["The Class Moves!"(R) - a hopefully promising step towards promoting child
      mobility].
AB  - To satisfy the considerable need of measures to improve mobility in childhood,
      the district of Heinsberg and the German-speaking Community Belgium started the
      programme " The Class Moves!"(R) at 10 each primary schools during the school
      year 2000/2001. The programme is based on "De klass beweegt!"(R) developed by a
      Dutch team led by physiotherapist Elise Sijthoff. This was translated into German
      and evaluated in an Interregg project. In conclusion, we may say that the method
      was well received by teachers, pupils, headmasters, school governors and parents.
      It can be easily integrated into the curriculum, exercises a positive influence
      on lessons, and is a suitable method to promote daily mobility at school.

PMID- 12221614
TI  - [Primary and secondary prevention of smoking in adolescents: results of the
      campaign "Be Smart - Don't Start"].
AB  - BACKGROUND: This paper examines the effectiveness of the "Smokefree Class
      Competition" with regard to primary and secondary prevention of smoking in
      adolescents. Each participating class has to decide if they want to be a
      "Smokefree Class" for the six-month period from fall to spring. Classes monitor
      their (non-)smoking behaviour and report it to the teacher regularly. Classes in
      which pupils refrain from smoking for this period of time participate in a prize
      draw, where they can win a number of attractive prizes. METHODS: A control group
      study with repeated measurements was carried out in order to evaluate the
      effectiveness of the competition. The sample consisted of 131 participating and
      non-participating classes ( N of the pupils = 2,142; mean age 12.9 years, SD =
      0.98). Smoking status was assessed on two occasions: (a) prior to the beginning
      of the competition, and (b) 6 month after the end of the competition. RESULTS:
      With regard to the smoking status at baseline no differences could be found
      between the experimental and the control group (15.2 % vs. 18.5 % smoking
      pupils). In the follow-up measurement, pupils in the control group showed
      significantly higher prevalences of smoking than the experimental group in the
      post-measurement period (32.9 % vs. 25.5 % smoking pupils). More pupils in the
      experimental group stayed smokefree compared to the control group. No
      differential effects on smoking cessation could be found. CONCLUSIONS: The
      results show that participation in the competition could delay the onset of
      smoking in adolescents (primary prevention). The competition is not effective in
      smoking cessation in youth.

PMID- 12221615
TI  - ["Fitness for public service" - results of standardised acceptance examinations].
AB  - From Nov. 1 1990 to Dec. 31 2001 4928 applicants (61 % female, 39 % male) were
      examined, totalling 6580 pre-employment examinations, to decide whether they
      fulfilled the health requirement criteria for civil servants. Standardised
      aptitude criteria were used, career-specific requirements taken into account. To
      exclude with a high probability were any risks of premature disability for
      service or frequent disorders. In 394 cases (= 5.99 %) the results were negative.
      This assessment was final in 298 cases (= 4.53 % of all examinations) or was
      confirmed negative in repeated examinations even after special conditions had
      been imposed. Main reasons for disqualification were second- and third-degree
      adipositas with additional risk factors or a metabolic syndrome, chronic cardio
      vascular and metabolic diseases requiring permanent treatment, malignant
      neoplasms or non-fulfilment of the criteria for special careers. The
      comparatively high rate of disqualification is mainly due to the high average age
      of the applicants examined (40 % of all applicants were over 40, 13 % were older
      than 50). Purpose, sensitivity and specifics of such examinations are discussed.
      Taking into consideration the high rate of civil servants prematurely unfit for
      work, such pre-employment examinations are regarded as highly justified.
      Moreover, it is necessary to have clear guidelines, aptitude criteria and
      examination procedures for individual careers. It is also important to adhere
      strictly to local responsibility for pre-employment examinations.

PMID- 12221616
TI  - [Early intervention in alcohol abuse and addiction in general acute care
      hospitals].
AB  - Early intervention has been shown to prevent alcohol-related diseases of the
      liver, the pancreas, and the gastrointestinal tract, as well as to reduce high
      blood pressure and the incidence of hospitalizations. At a general hospital, 27
      patients were offered addiction counselling, six of whom were successfully
      referred to an outpatient addiction counsellor. However, prevalence rates of
      alcohol abuse and addiction were significantly lower than those reported in other
      studies. Similarly, referrals to addiction counselling were less frequent than in
      other programmes in which hospital staff had been specifically trained to
      identify problems of alcohol abuse and addiction and to initiate timely
      referrals. Intensive training of hospital staff as well as the provision of
      personal and logistical support at the hospital is crucial in the implementation
      of early intervention programmes for alcohol abuse and addiction in general
      hospitals.

PMID- 12221617
TI  - [Post stroke depression: predictive factors at one year follow up].
AB  - INTRODUCTION: The presence of depression constitutes one of the treatable
      complications in stroke survivors. Its long term prevalence and the triggering
      factors are unknown in our community. Moreover, its presence can interfere in the
      process of rehabilitating the patient and in family dynamics. PATIENTS AND
      METHODS: A sample of 118 patients from the Stroke Unit at the Hospital
      Universitario San Carlos in Madrid were studied. After one year follow up, 90
      survivors (41 females and 49 males; average age: 68 years) were evaluated, with
      their informed consent, with the Hamilton depression and Beck s melancholia
      scale, the Barthel index, the Rankin scale, Psychosocial Dimension of Sickness
      Impact Profile and the Scandinavian neurological scale. A factorial ANOVA model
      was used to conduct the statistical analysis. RESULTS: On discharge, a third of
      the patients presented symptoms of depression, while a year after the stroke the
      figure had risen to 67%. The average score on the Hamilton scale at one year
      follow up was 13.1 and was rated as mild depression. The variables related with
      depression one year after the stroke were of a socio demographic nature (female,
      women working in the home, long lasting occupational disability; p< 0.0001),
      whereas biological variables (cortical/subcortical distribution, laterality,
      aetiology and subtype of the stroke) were not statistically significant. Subjects
      suffering from serious disabilities that affected the performance of their daily
      activities (Barthel< 60) scored significantly worse (p= 0.005). Motor deficit,
      according to the Scandinavian scale, was of no use as a predictor of depression
      one year after the stroke (p= 0.0617). CONCLUSIONS: Post stroke depression is
      highly prevalent in our community and, late on in the follow up, is associated
      with socio demographic variables and with the degree of disability.

PMID- 12221618
TI  - [Transient ischemic attacks: risk factors, duration and neuroimaging in a series
      of 173 patients].
AB  - INTRODUCTION: The appearance of transient ischemic attacks (TIA) is an important
      sign of vascular risk. The maximum time the deficit lasts has been set
      arbitrarily at 24 hours. It is assumed that TIA does not entail permanent
      vascular lesions. PATIENTS AND METHODS: A retrospective review of the clinical
      records of patients diagnosed as suffering from TIA in our centre between 1996
      and 1997. Analysis of associated risk factors (RF), duration and findings in
      neuroimaging. RESULTS: The clinical records of 173 patients (106 males) were
      examined. The RF identified were similar to those described for ischemic strokes.
      45.6% of patients with a history of vascular pathologies received no preventative
      treatment. 58% of the TIA were resolved within the first 30 minutes and 71%
      within the first hour. Cranial CT was normal in 69%, showed old lesions in 26%
      and lesions that were compatible with the clinical signs of TIA in 5% (in the
      latter case the duration of the episodes was greater). CONCLUSIONS: TIA shares
      the same RF and aetiopathogenic mechanisms as ischemic stroke and should,
      therefore, be considered as such. There is a need to revise the concept of TIA
      paying special attention to the findings of neuroimaging or to establish duration
      limits that are better matched to the practical reality. TIA maintains a
      practical interest since it provides a simple method of identifying patients with
      a high vascular risk.

PMID- 12221619
TI  - [Time analysis of mortality from cerebrovascular diseases in Andalucia (1975
      1999)].
AB  - INTRODUCTION: In previous publications we analysed the tendency of mortality from
      cerebrovascular diseases (CVD) in Andalusia over the period 1975-1992, and we
      observed a marked decrease in the mortality rates in both sexes. AIMS. To
      describe the evolution of mortality from CVD in Andalusia throughout the period
      1975-1999. PATIENTS AND METHODS: Deaths from CVD over the period 1975 1999 were
      obtained from the Instituto Andaluz de Estadistica. We employed the direct method
      of standardisation of rates (world standard population). The rates were subjected
      to logarithmic transformations and the regression lines were adjusted. RESULTS: A
      considerable decrease was found in the rates: 3.9% in males and 4.0% in females.
      The drop in truncated rates (35 64 years old) was greater in women ( 5.9%) than
      in men ( 4.3%). CONCLUSIONS: Our work shows a marked and continuous decrease in
      mortality from CVD in Andalusia (1975-1999). In accordance with the process of
      aging of the population, the magnitude of CVD measured in terms of deaths,
      invalidity and health costs still represents a great challenge for preventative
      and health care policies.

PMID- 12221620
TI  - [Hemispheric dominance for language and functional magnetic resonance: a
      comparison of three tasks].
AB  - OBJECTIVE: The object of this study to analyse and compare the efficacy of the
      classic language tasks (repetition, phonological fluency and lexical decision),
      for the purpose of identifying the dominant hemisphere for language by means of
      functional magnetic resonance. SUBJECTS AND METHODS: The three tasks were
      performance with a groups of 10 right handed subjects with ages of 22 to 40
      years. The examination was carried out using a 1,5 T MRI apparatus. An eight
      sequence of planar echo gradient (BOLD technique) was used, making the oblique
      axial plane coincide with the line between the anterior and posterior commissures
      (CA CP line) and covering the entire brain. RESULTS: Dominance was calculated by
      means of the lateralization index, comparing the activation in each hemisphere in
      two locations: first, taking account the temporal lobe together with the right
      and left frontal lobes, and second, taking into account only the right and left
      frontal lobes. CONCLUSION: The result indicate that the most effective test for
      obtaining the dominant hemisphere was the one for phonological fluency, this task
      activated the frontal areas, which showed greater participation in the left
      hemisphere.

PMID- 12221621
TI  - [Thymectomy in juvenile myasthenia gravis].
AB  - INTRODUCTION: Juvenile myasthenia gravis (JMG) is an infrequent autoimmune
      disease, the symptoms and therapeutic handling of which do not differ from those
      of the adult forms. Chronic treatment with corticoids very often causes side
      effects in childhood, which is why patients are being submitted to thymectomies
      at younger ages with better results. AIMS. To analyse the clinical and
      evolutionary profile of JMG treated by thymectomy in our centre. PATIENTS AND
      METHODS: We report the case of four girls aged between 5 and 13 who were
      diagnosed as suffering from generalised myasthenia gravis (MG) with bulbar
      affectation. One of them started with a myasthenic crisis. The four of them were
      submitted to Tensilon s test, an electrophysiological study, determination of
      AChR, thoracic CT, and study of autoimmunity and thyroid functioning. After
      surgery the thymus was analysed histologically. RESULTS: They all gave positive
      in Tensilon s test and were seropositive for AChR. They were treated with
      anticholinesterases, up to the maximum tolerated dose, and corticoids, without
      complete remission being accomplished and so they were submitted to a thymectomy
      in the first year of evolution. In three cases surgical approach was transsternal
      and in the other by means of a videothoracoscope. All the thymuses showed
      lymphoid hyperplasia. After a variable follow up the girls are at present
      asymptomatic, although none of them has been able to completely give up the
      pharmacological treatment. CONCLUSIONS: Thymectomy is one of the mainstays of
      treatment for JMG. The ever more frequent use of videothoracoscopic techniques
      achieves results that are similar to those obtained by conventional surgery but
      with fewer post operative and aesthetic problems

PMID- 12221622
TI  - [Chronic subdural haematoma. Presentation and therapeutic attitudes].
AB  - INTRODUCTION: The chronic subdural haematoma (CSH) is a present pathology in the
      day by day of any Neurosurgical Department, and even in the beginning of the xxi
      century, the different therapeutic options are of current debate. OBJECTIVE: To
      compare retrospectively the results obtained by different types of surgical
      techniques, different modalities of drainage systems, and the application or not
      of perioperative intrathecal solutions. PATIENTS AND METHODS: The data have been
      obtained by the review of 109 clinical cases treated of CSH between 1996 and 2000
      in the Department of Neurosurgery of the Hospital de Cruces (Bilbao). We have
      analysed the age, sex, background, presenting symptomatology, type of treatment,
      evolution and mean hospital stay. RESULTS: The report is centred in the analysis
      of the recurrence rate of the CSH, its principal feature, and so, according to
      the type of evacuation technique, a burr hole presents 17,2% recurrences, two
      burr holes 31%, a small craniotomy 50%, and an ordinary craniotomy 66%. According
      to the drainage system, the subgaleal shunt presents 33,3% recurrences, the
      subdural 24,5%, and the subdural subgaleal 15,4%. The intrathecal solutions
      present 37% recurrences. CONCLUSION: After studying all the data, we can conclude
      that for the treatment of the CSH, the choice of a burr hole and subdural
      subgaleal shunt and intrathecal solution, can result beneficial in relation to
      other techniques, although with a minimum difference over the subdural shunt.

PMID- 12221623
TI  - [Systemic lupus erythematosus with affection to brainstem: report of three
      cases].
AB  - INTRODUCTION: The frequency with which the central nervous system (CNS) is
      affected by systemic lupus erythematosus (SLE) varies, according to different
      series, between 13 and 59%, whereas the brain stem is affected in 5%. CASE
      REPORTS: Case 1: a 33 year old male who was submitted to a Nissen funduplicature
      as a treatment of (hypo)incoercible hiccups. The singultus persisted and some
      time after a paraplegia appeared. Magnetic resonance (MRI) showed images in the
      medulla oblongata, and in the cervical and thoracic spine. A biopsy was also
      performed to examine the cervical lesions and vasculitis was diagnosed. The
      patient began treatment with prednisone (1 mg/kg) and two months after symptoms
      had begun to improve he presented an episode of bilateral optic neuritis. Until
      this last event, the immunological studies had been positive. Case 2: female aged
      19 who had had SLE for eight months. The illness began suddenly with bilateral
      paralysis of the sixth cranial nerve, vertical and horizontal nystagmus,
      dysdiadochokinesia, truncal ataxia, 4/5 muscular strength in the upper limbs and
      3/5 in the lower limbs, and left flexor plantar response, but indifferent on the
      right hand side. MR showed T2 hyperintensities in the pons, medulla oblongata and
      the junction of medulla and upper spinal cord. Case 3: female aged 31 with sudden
      onset of the illness, characterised by diplopy and presence of internuclear
      ophthalmoplegia. Brain MR showed images of T1 hypointense and T2 hyperintense in
      the pontobulbar region. CONCLUSION: A brain stem disorder in patients suffering
      from SLE is one of the rarest manifestations of this pathological condition of
      the CNS and is probably caused by vasculitis

PMID- 12221624
TI  - [Schwartz-Jampel syndrome: a description of two adult siblings].
AB  - INTRODUCTION: Schwartz Jampel syndrome is a usually recessive disorder that
      presents myotonia, skeletal (bone dysplasia) and facial (blepharophimosis)
      anomalies and low height, which is diagnosed in childhood. We report on the
      clinical, electromyographical and radiological findings of two siblings affected
      by the disease and who were diagnosed late, in adulthood. CASE REPORTS: Two
      siblings, a male aged 39 and a female of 49, the only members of a family of five
      siblings born to consanguineous parents to be affected, were studied because of
      deformities in the joints that appeared at the age of nine months and alterations
      in their gait. Both had a syndromic facies with hypertelorism, micrognathia,
      blepharospasm, thin mouth, saddle nose and low height. The sister presented
      lumbar hyperlordosis, dislocation of the kneecaps, clubfeet, fists with radial
      deviation, bilateral dislocation of the head of the radius and limited
      pronosupination and flexure tension of the elbow. Deep reflexes were diminished.
      The male had deformities in both knees and in the right elbow, and was unable to
      perform pronosupination of the arm or bend the knee. A coxofemoral X ray revealed
      an epiphysial dysplasia. The magnetoencephalogram showed continuous muscular
      activity with complex repetitive discharges in the sister s orbicularis oculi and
      biceps. The brother had a bilateral entrapment of the ulnar nerve in the ulnar
      canal with a secondary axonal compromise. Magnetic resonance imaging of the
      encephalon of the patient showed cortical atrophy, hyperintense focal areas in
      the periventricular white matter and platybasia. CONCLUSIONS: In the adult,
      myotonic chondrodystrophia evolves with decreased blepharospasm, the presence of
      structured deformities and entrapments of peripheral nerves.

PMID- 12221625
TI  - [Mechanisms of generation of fast (20 80 Hz) oscillations in thalamocortical
      circuits].
AB  - AIM: This review focuses on the mechanisms of generation of fast (20 80 Hz)
      oscillations in thalamocortical networks and their possible functional role.
      DEVELOPMENT: Fast oscillations appear in the electroencephalogram in a transitory
      fashion, during behavioral tasks that require increased alertness or during
      responses to optimal sensory stimulation in animals and humans. Fast oscillations
      also appear spontaneously during activated states (awake state and paradoxical
      sleep) and during the depolarizing phases of the slow oscillation that
      characterize slow wave sleep and anesthesia. Fast oscillations are generated in
      thalamic and cortical circuits as the result of the activity of pacemaker cells,
      or as the result of the synaptic interactions among excitatory and inhibitory
      cells. The synchronization of fast oscillations has been proposed as a possible
      solution to the binding problem. The formation of neuronal ensembles containing
      specific sets of cells oscillating together would be the code representing
      sensory input and coordination between sensory and motor activity. However,
      oscillating neurons coexist with equal numbers of non oscillating neurons.
      CONCLUSIONS: Understanding the rules of coexistence of these two regimes of
      network activity is key to understanding information processing in the brain. As
      a first step, and in order to understand the possible role of fast oscillations,
      it is necessary to understand the mechanisms by which they are generated.

PMID- 12221626
TI  - [Physiopathology of adult onset external hydrocephalus].
AB  - AIMS: In this paper we report on a new disorder known as adult onset external
      hydrocephalus. DEVELOPMENT: There is sufficient evidence to be able to establish
      the pathogenic hypotheses proposed here. Adult onset external hydrocephalus is
      related with traumatic injuries, surgery, subarachnoid haemorrhages and
      neurosurgical treatment of aneurysms. This disorder is produced by an expansion
      of the subarachnoid and subdural space due to the rupture of some part of the
      arachnoid membrane, which then allows fluid to flow into this compartment. In all
      cases there are three essential factors: the presence of some kind of
      intracranial bleeding, tearing of the arachnoid membrane and an excessive
      quantity of cerebrospinal fluid (CSF), probably because of reduced reabsorption
      by the arachnoid granulations. The degree to which reabsorption of CSF is
      affected is what conditions the prognosis in these patients rather than the
      accumulation within the subarachnoid or subdural cavity. Once this type of
      hydrocephalus is confirmed the patient requires a ventricular CSF shunt. We offer
      a classification of the different types of presentation. It is not very clear
      exactly when this shunt should be inserted or how to treat the isolated extra
      axial collection in absence of ventricular dilatation. CONCLUSIONS: The
      physiopathology of adult onset external hydrocephalus is a scientific challenge
      that will lay down the foundations for treatment with ventriculoperitoneal shunts

PMID- 12221627
TI  - [Pediatric neurology and genetics: introduction].
AB  - INTRODUCTION: Heredity plays a role in a large proportion of pediatric neurologic
      disorders, and the spectacular recent developments in molecular genetics have
      contributed to improved understanding of the basic causes of many diseases and
      neurodevelopmental abnormalities. OBJECTIVE: To provide a brief introduction to
      certain genetic aspects of neuropediatrics. DEVELOPMENT: We consider the
      following aspects: 1) The importance of hereditary factors in pediatric
      neurology; 2) The different types of inheritance relevant in this context; 3)
      Nosologic, diagnostic and therapeutic implications of recent advances in
      molecular genetics; 4) Bioethical implications of the application of this new
      understanding. CONCLUSIONS: Independently of enhanced treatment prospects,
      progress in molecular genetics has improved the nosology and diagnosis of many
      pediatric neurological disorders.

PMID- 12221628
TI  - [The contribution of molecular genetics to hereditary neurometabolic disorders].
AB  - In this article we review the main contribution of molecular genetics to
      understanding hereditary neurometabolic disorders. This includes improvement in
      diagnosis, especially in X chromosome linked disorders and illness due to the
      protein or gene expression in tissues which are difficult to obtain. Moreover
      molecular biology, as a diagnostic tool, has contributed decisively to genetic
      counselling by permitting firm diagnosis of carriers and prenatal diagnosis.
      Other important contributions, although more minor, are determination of the
      prognosis and establishment of individualized treatment based on the genotype. We
      also review the relation between the disease and the susceptibility allele, the
      possibility of making genetic population studies and of establishing
      presymptomatic diagnoses. It is concluded that understanding the molecular basis
      of a particular disorder has opened the way to diagnosis and prognosis. It also
      opens the door to genetic therapy, the study of other factors which may affect
      the action of genes and especially the proteinome.

PMID- 12221629
TI  - [Molecular genetics of disorders of the mitochondrial respiratory chain].
AB  - Mitochondria have a key role in cell metabolism, being the major site of ATP
      production via oxidative phosphorylation. This system consists of five
      multiprotein complexes, whose individuals subunits are encoded either by the
      mitochondrial or by the nuclear genome. Respiratory chain enzyme deficiencies
      result in devastating, usually multisystem, disorders. Recently, many underlying
      mutations in mitochondrial and nuclear genes have been described at a brisk pace
      as a result of the advances in the knowledge of molecular genetics.

PMID- 12221630
TI  - [Prospects for gene treatment in paediatric neurology].
AB  - INTRODUCTION: The current advances in the field of human genetics allow for the
      development of alternative therapies for the treatment of diseases affecting the
      central nervous system (CNS). One of the most promising new therapies is the use
      of therapeutic genes or gene therapy. OBJECTIVE: To briefly review the recent
      advances for the treatment of diseases affecting the CNS. DEVELOPMENT: We
      consider the therapeutic strategies currently in study for gene therapy of
      diseases with neurologic symptoms as monogenic diseases, CNS malignancies and
      neurodegenerative diseases. We describe the pros and cons of viral, non viral
      vectors and cell based therapy. CONCLUSIONS: The current gene therapy approaches
      allow for specific and efficient administration of therapeutic genes to the CNS.
      Despite the need of optimization of the available vectors, mainly regarding to
      safety and efficacy, gene therapy has an important potential for the treatment of
      neuropediatric diseases.

PMID- 12221632
TI  - [Myopathy caused by colchicine with myotonia].

PMID- 12221633
TI  - [Can hypervoltage waves exist in brain stem auditory evoked potentials?].

PMID- 12221634
TI  - [Progression of an astrocytoma throughout the pyramidal pathway].

PMID- 12221635
TI  - [Diploid triploid mosaicism with epilepsy and mental retardation: exceptional
      survival up to adulthood].

PMID- 12221638
TI  - Feline immunodeficiency virus vectors. Gene transfer to mouse retina following
      intravitreal injection.
AB  - BACKGROUND: Transduction of the murine retinal pigmented epithelium (RPE) with
      adenovirus vectors requires technically difficult and invasive subretinal
      injections. This study tested the hypothesis that recombinant vectors based on
      feline immunodeficiency virus (FIV) could access the retina following
      intravitreal injection. METHODS: FIV vectors expressing E. coli beta
      galactosidase (FIVbetagal) were injected alone, or in combination with adenovirus
      vectors expressing eGFP, into the vitreous of normal mice and eyes evaluated for
      transgene expression. In further studies, the utility of FIV-mediated gene
      transfer to correct lysosomal storage defects in the anterior and posterior
      chambers of eyes was tested using recombinant FIV vectors expressing beta
      glucuronidase. FIVbetagluc vectors were injected into beta-glucuronidase
      deficient mice, an animal model of mucopolysacharridoses type VII. RESULTS: The
      results of this study show that similar to adenovirus, both corneal endothelium
      and cells of the iris could be transduced following intravitreal injection of
      FIVbetagal. However, in contrast to adenovirus, intravitreal injection of
      FIVbetagal also resulted in transduction of the RPE. Immunohistochemistry
      following an intravitreal injection of an AdeGFP (adenovirus expressing green
      fluorescent protein) and FIVbetagal mixture confirmed that both viruses mediated
      transduction of corneal endothelium and cells of the iris, while only FIVbetagal
      transduced cells in the retina. Using the beta-glucuronidase-deficient mouse, the
      therapeutic efficacy of intravitreal injection of FIVbetagluc (FIV expressing
      beta-glucuronidase) was tested. Intravitreal injection of FIVbetagluc to the eyes
      of beta-glucuronidase-deficient mice resulted in rapid reduction (within 2 weeks)
      of the lysosomal storage defect within the RPE, corneal endothelium, and the non
      pigmented epithelium of the ciliary process. Transgene expression and correction
      of the lysosomal storage defect remained for at least 12 weeks, the latest time
      point tested. CONCLUSION: These studies demonstrate that intravitreal injection
      of FIV-based vectors can mediate efficient and lasting transduction of cells in
      the cornea, iris, and retina.

PMID- 12221639
TI  - Introduction of the green fluorescent protein gene into hematopoietic stem cells
      results in prolonged discrepancy of in vivo transduction levels between bone
      marrow progenitors and peripheral blood cells in nonhuman primates.
AB  - BACKGROUND: The green fluorescent protein (GFP) has proven a useful marker in
      retroviral gene transfer studies targeting hematopoietic stem cells (HSCs) in
      mice. However, several investigators have reported very low in vivo peripheral
      blood marking levels in nonhuman primates after transplantation of HSCs
      transduced with the GFP gene. We retrovirally marked cynomolgus monkey HSCs with
      the GFP gene, and tracked in vivo marking levels within both bone marrow
      progenitor cells and mature peripheral blood cells following autologous
      transplantation after myeloablative conditioning. METHODS: Bone marrow cells were
      harvested from three cynomolgus macaques and enriched for the primitive fraction
      by CD34 selection. CD34(+) cells were transduced with one of three retroviral
      vectors all expressing the GFP gene and were infused after myeloablative total
      body irradiation (500 cGy x 2). Following transplantation, proviral levels and
      fluorescence were monitored among clonogenic bone marrow progenitors and mature
      peripheral blood cells. RESULTS: Although 13-37% of transduced cells contained
      the GFP provirus and 11-13% fluoresced ex vivo, both provirus and fluorescence
      became almost undetectable in the peripheral blood within several months after
      transplantation regardless of the vectors used. However, on sampling of bone
      marrow at multiple time points, significant fractions (5-10%) of clonogenic
      progenitors contained the provirus and fluoresced ex vivo reflecting a
      significant discrepancy between GFP gene marking levels within bone marrow cells
      and their mature peripheral blood progeny. The discrepancy (at least one log)
      persisted for more than 1 year after transplantation. Since no cytotoxic T
      lymphocytes against GFP were detected in the animals, an immune response against
      GFP is an unlikely explanation for the low levels of transduced peripheral blood
      cells. Administration of granulocyte colony stimulating factor and stem cell
      factor resulted in mobilization of transduced bone marrow cells detectable as
      mature granulocyte progeny which expressed the GFP gene, suggesting that
      transduced progenitor cells in bone marrow could be mobilized into the peripheral
      blood and differentiated into granulocytes. CONCLUSIONS: Low levels of GFP
      transduced mature cells in the peripheral blood of nonhuman primates may reflect
      a block to differentiation associated with GFP; this block can be overcome in
      part by nonphysiological cytokine treatment ex vivo and in vivo.

PMID- 12221640
TI  - Reporter genes: too much of a good thing?
AB  - Advances in viral vector design and identification of new reporter genes have
      allowed the development of novel delivery systems. In the presence of reporter
      genes, cellular transduction frequency, expression of the gene of interest and
      phenotypic effects in cells expressing the gene under study can now be easily
      monitored both in vitro and in vivo. Moreover, the presence of unique cell
      markers allows for the enrichment of transduced cells for research studies or
      patient infusion. The ideal reporter gene product should be biologically inert
      and not influence the cell population under investigation. Recent reports suggest
      that reporter gene products may not be biologically benign.

PMID- 12221641
TI  - Gutted adenoviral vector growth using E1/E2b/E3-deleted helper viruses.
AB  - BACKGROUND: Helper-dependent, or gutted, adenoviruses (Ad) lack viral coding
      sequences, resulting in reduced immunotoxicity compared with conventional Ad
      vectors. Gutted Ad growth requires a conventional Ad to supply replication and
      packaging functions in trans. Methods that allow high-titer growth of gutted
      vectors while reducing helper contamination, and which use safer helper viruses,
      will facilitate the use of gutted Ad vectors in vivo. METHODS: Replication
      defective helper viruses were generated that are deleted for Ad E1, E2b and E3
      genes, but which contain loxP sites flanking the packaging signal. Complementing
      Ad packaging cell lines (C7-cre cells) were also generated by transfecting 293
      cells with the Ad E2b genes encoding DNA polymerase and pre-terminal protein, and
      with a cre-recombinase plasmid. RESULTS: We show that C7-cre cells allow
      efficient production of gutted Ad using deltaE1 + deltaE2b + deltaE3 helper
      viruses whose growth can be limited by cre-loxP-mediated excision of the
      packaging signal. Gutted Ad vectors carrying approximately 28 kb cassettes
      expressing full-length dystrophin were prepared at high titers, similar to those
      obtained with E2b+ helpers, with a resulting helper contamination of <1%.
      CONCLUSIONS: These new packaging cell lines and helper viruses offer several
      significant advantages for gutted Ad vector production. They allow gutted virus
      amplification using a reduced number of passages, which should reduce the chances
      of selecting rearranged products. Furthermore, the residual helper contamination
      in gutted vector preparations should be less able to elicit immunological
      reactions upon delivery to tissues, since E2b-deleted vectors display a profound
      reduction in viral gene expression.

PMID- 12221642
TI  - Adeno-cosmid cloning vectors for regulated gene expression.
AB  - BACKGROUND: Adenovectors are widely used for efficient delivery of genes into a
      variety of cell types and organisms. However, the construction of the desired
      vector/genes combination, especially if it involves the cloning of several gene
      cassettes, can be laborious due to the large size of these vectors. New methods
      are needed to simplify the construction of complex combinations of gene cassettes
      into adenovectors. METHODS: Using simple cloning techniques and exploiting the
      lambda-phage packaging system, we devised efficient methods for the 'selection'
      of the desired vector constructs. Thus we generated a series of cosmids
      containing the adeno helper dependent (HD) backbone in which we inserted cis- and
      trans-acting tetracycline (tet) elements for the regulation of any gene of
      interest. One of these cosmids has been used to produce an HD adenovirus carrying
      a tetracycline-regulated gene expressing beta-galactosidase. RESULTS: We have
      demonstrated that the adeno-cosmid system allows rapid and efficient cloning of
      genes of interest in helper dependent vectors, and described a prototype 'ready
      to-use' vector in which any gene of interest can be easily expressed under the
      control of the tet system. The HD viruses produced with this novel methodology
      can be grown at high titers, can be easily separated from the helper adenovirus,
      and allow delivery and regulated gene expression in a variety of tissues.
      CONCLUSIONS: Exploiting the lambda-packaging system, complex adeno constructs can
      be generated with a simple and reproducible protocol, which allows selection of
      the desired size construct, counterselecting for the frequently observed
      intramolecular recombinations and deletions.

PMID- 12221643
TI  - Production of helper-dependent adenovirus vector relies on helper virus structure
      and complementing.
AB  - BACKGROUND: The helper-dependent (HD) adenoviral (Ad) vector relies on a helper
      virus to provide viral proteins for vector amplification. HD-Ad vectors can
      significantly increase therapeutic gene expression and improve safety. However,
      the yield of an HD-Ad vector is generally lower than that of an E1-deleted first
      generation vector, likely due to the alterations in viral E3 or packaging regions
      of a helper virus that attenuate its replication and complementing for an HD-Ad
      vector. METHODS: To study this question and improve HD-Ad vector production, we
      have generated four different helper viruses with a wild-type or deleted E3
      region, and with a relocated loxP. We have also constructed a first-generation
      vector with a wild-type E3 region and without the loxP site. We compared the
      replication of these viruses in Cre-positive and -negative cells and studied
      their complementing for HD-Ad vector production. RESULTS: Viruses with deleted E3
      formed smaller plaques and produced lower titer compared with viruses containing
      the E3 region. The site where a loxP is inserted can also affect virus
      replication. Higher yield of HD-Ad vector was obtained when a helper virus with
      wild-type E3 was used. We also showed that deletion of the packaging signal in a
      helper virus through loxP/Cre interaction decreased the viral DNA complementing
      ability. CONCLUSIONS: Although the E3 region is not essential for adenovirus
      replication in vivo, deletion of this region attenuates virus replication.
      Production of HD-Ad vector can be further improved by modifications in helper
      virus structure.

PMID- 12221644
TI  - Epidermal growth factor receptor targeting enhances adenoviral vector based
      suicide gene therapy of osteosarcoma.
AB  - BACKGROUND: Despite improvements in the treatment of osteosarcoma (OS) there are
      still too many patients who cannot benefit from current treatment modalities.
      Therefore, new therapeutic approaches are warranted. Here we explore the efficacy
      of targeted adenoviral based suicide gene therapy. METHODS AND RESULTS:
      Immunohistochemistry and FACS analysis detected low or absent expression levels
      of the primary adenovirus receptor CAR on human primary OS and human OS cell
      lines. These results predict a low infection efficiency and thus a reduced
      therapeutic effect. Targeting the adenoviruses to another receptor highly
      expressed on OS could overcome this limitation. We found epidermal growth factor
      receptor (EGFR) to be widely expressed on primary OS. Immunohistochemistry on
      primary tumor samples and FACS analysis on primary short-term cultures and four
      OS cell lines showed that EGFR was consistently expressed. The recombinant
      bispecific single-chain antibody 425-s11 redirects adenoviral vectors towards the
      EGFR. Adenovirus transduction experiments in the presence or absence of 425-s11
      showed significantly enhanced gene transfer with the targeted adenoviral vector
      compared with the native vector (OS cell lines 2.5 to 7.2 times enhanced gene
      transfer and OS primary short term cultures 1.7 to 10 times enhanced gene
      transfer). On this basis, targeted suicide gene therapy experiments with AdCMVHSV
      TK in combination with ganciclovir were performed. These experiments demonstrated
      up to 3.5-fold enhanced kill of OS cell lines and primary short-term cultures by
      the EGFR targeted vector. CONCLUSIONS: Suicide gene therapy with adenovirus
      targeted towards EGFR may have favorable therapeutic characteristics for future
      gene therapy applications in OS.

PMID- 12221645
TI  - Aminoglycoside-derived cationic lipids as efficient vectors for gene transfection
      in vitro and in vivo.
AB  - BACKGROUND: Cationic lipids are at present very actively investigated for gene
      transfer studies and gene therapy applications. Basically, they rely on the
      formation of DNA/lipid aggregates via electrostatic interactions between their
      cationic headgroup and the negatively charged DNA. Although their
      structure/activity relationships are not well understood, it is generally agreed
      that the nature of the positive headgroup impacts on their transfection activity.
      Thus, we have directed our efforts toward the development of cationic lipids with
      novel cationic moieties. In the present work, we have explored the transfection
      potential of the lipophilic derivatives of the aminoglycoside kanamycin A.
      Indeed, aminoglycosides, which are natural polyamines known to bind to nucleic
      acids, provide a favorable scaffold for the synthesis of a variety of cationic
      lipids because of their structural features and multifunctional nature. METHODS
      AND RESULTS: We report here the synthesis of a cationic cholesterol derivative
      characterized by a kanamycin A headgroup and of its polyguanidinylated
      derivative. The amino-sugar-based cationic lipid is highly efficient for gene
      transfection into a variety of mammalian cell lines when used either alone or as
      a liposomal formulation with the neutral phospholipid
      dioleoylphosphatidylethanolamine (DOPE). Its polyguanidinylated derivative was
      also found to mediate in vitro gene transfection. In addition, colloidally stable
      kanamycin-cholesterol/DOPE lipoplexes were found to be efficient for gene
      transfection into the mouse airways in vivo. CONCLUSIONS: These results reveal
      the usefulness of cationic lipids characterized by headgroups composed of an
      aminoglycoside or its guanidinylated derivative for gene transfection in vitro
      and in vivo.

PMID- 12221646
TI  - Targeted gene therapy for rat glomerulonephritis using HVJ-immunoliposomes.
AB  - BACKGROUND: Kidney targeted gene transfer has been attempted by many researchers
      over the last 10 years; however, unfortunately, no reliable technique for gene
      transfer to the kidney has been established. At experimental level several in
      vivo gene transfer methods have been reported. METHODS: We were the first to
      report successful in vivo gene transfer into the kidney using the HVJ-liposome
      method. Since then, this method has been modified to achieve highly efficient
      gene transfer. In this study, we have developed a renal glomerulus-specific gene
      transfer method using HVJ-liposomes with anti-Thy 1 antibody, OX-7. RESULTS:
      Following systemic delivery of fluoroisothiocyanate (FITC)-labeled
      oligodeoxynucleotides (ODN) by HVJ-liposomes coupled with OX-7, we observed
      fluorescence in renal glomeruli from 2 h post-administration. To examine the
      efficacy of this delivery system, NF-kappaB or scrambled (SD) decoy ODN was
      administered by HVJ-liposomes coupled with OX-7 into a crescent
      glomerulonephritis, anti-glomerular basement membrane (GBM) model. Animals given
      SD decoy ODN developed severe glomerulonephritis by day 7 with heavy albuminuria,
      glomerular crescent formation and up-regulated renal expression of IL-1beta and
      ICAM-1. In contrast, NF-kappaB decoy ODN treatment substantially inhibited the
      disease with a reduction in alubuminuria, histological damage and the renal
      expression of inflammatory cytokines. CONCLUSIONS: This study has demonstrated
      that systemic delivery of HVJ-liposomes coupled with OX-7 results in efficient
      ODN transfer in rat glomeruli. NF-kappaB, but not SD decoy ODN administered
      systemically via HVJ-liposomes complexed with OX-7 showed clear therapeutic
      potential for glomerulonephritis. This novel ODN transfer method combined with
      decoy strategy has the potential to lead to the establishment of a new
      therapeutic approach to glomerular diseases.

PMID- 12221647
TI  - Modification of pLL/DNA complexes with a multivalent hydrophilic polymer permits
      folate-mediated targeting in vitro and prolonged plasma circulation in vivo.
AB  - BACKGROUND: Gene delivery vectors based on poly(L-lysine) and DNA (pLL/DNA
      complexes) have limited use for targeted systemic application in vivo since they
      bind cells and proteins non-specifically. In this study we have attempted to form
      folate-targeted vectors with extended systemic circulation by surface
      modification of pLL/DNA complexes with hydrophilic polymers. METHODS: pLL/DNA
      complexes were stabilised by surface modification with a multivalent reactive
      polymer based on alternating segments of poly(ethylene glycol) and tripeptides
      bearing reactive ester groups. Folate moieties were incorporated into the vectors
      either by direct attachment of folate to the polymer or via intermediate
      poly(ethylene glycol) spacers of 800 and 3400 Da. RESULTS: Polymer-coated
      complexes show similar morphology to uncoated complexes, their zeta potential is
      decreased towards zero, serum protein binding is inhibited and aqueous solubility
      is substantially increased. Intravenous (i.v.) administration to mice of coated
      complexes produced extended systemic circulation, with up to 2000-fold more DNA
      measured in the bloodstream after 30 min compared with simple pLL/DNA complexes.
      In further contrast to simple pLL/DNA complexes, coated complexes do not bind
      blood cells in vivo. Folate receptor targeting is shown to mediate targeted
      association with HeLa cells in vitro, leading to increased transgene expression.
      We demonstrate for the first time that DNA uptake via the folate receptor is
      dependent on pEG spacer length, with the transgene expression relatively
      independent of the level of internalised DNA. CONCLUSIONS: We show increased
      systemic circulation, decreased blood cell and protein binding, and folate
      targeted transgene expression using pLL/DNA complexes surface-modified with a
      novel multireactive hydrophilic polymer. This work provides the basis for the
      development of plasma-circulating targeted vectors for in vivo applications.

PMID- 12221648
TI  - Zinc improves gene transfer mediated by DNA/cationic polymer complexes.
AB  - BACKGROUND: The weak efficiency of plasmid transfer into the cytosol remains one
      of the major limiting factors to achieve an efficient transfection with
      DNA/cationic polymer complexes. We found that divalent metal Zn2+ can improve the
      polyfection efficiency, especially with DNA/histidylated polylysine (His-pLK)
      complexes. METHODS AND RESULTS: The supplementation of the transfection medium
      with 250 micro M ZnCl2 increased the polyfection of human hepatocarcinoma (HepG2)
      cells with a plasmid encoding EGFP complexed with pLK, polyethyleneimine and His
      pLK. Zn2+ is more efficient on DNA/His-pLK complexes: the number of EGFP-positive
      cells increased from 1% to more than 40%. This phenomenon is selective to Zn2+
      because no effect was obtained with other divalent cations. The effect of zinc
      varies from cell to cell. The binding of Zn2+ to histidyl residues might increase
      zinc endosomal concentration favoring membrane fusion. Flow cytometry and
      confocal microscopy studies clearly indicate that with His-pLK, the plasmid is
      better delivered in the cytosol as well as in the cell nucleus in zinc-treated
      cells. An investigation conducted with the histidine-rich peptide H5WYG showed
      that zinc inhibits membrane permeabilization but promotes membrane fusion as
      evidenced by resonance energy transfer. CONCLUSIONS: Data reported here imply
      that the addition of zinc ions in the transfection medium can trigger an increase
      of the fusion of endosomes containing polyplexes which is more effective in the
      presence of histidine-rich molecules. Consequently, the amount of plasmid in the
      cytosol available to reach the nucleus is increased leading to an improvement of
      polyfection.

PMID- 12221649
TI  - Transfer of maternally administered fusogenic liposome-DNA complexes into monkey
      fetuses in a pregnancy model.
AB  - BACKGROUND: Materno-fetal transfer of intravenously administered liposome-plasmid
      DNA complexes has been demonstrated only in mice. Studies on its materno-fetal
      transfer in the pregnant monkey model is needed because of critical differences
      in placental structure between primates including humans and rodents. METHODS:
      The reporter plasmid pEGFP-C1 was formulated in cationic lipid containing
      polybrene and vesicular stomatitis virus G protein. The fusogenic liposome
      plasmid DNA complexes were intradermally injected into pregnant common marmosets
      (N=2), a New World monkey, near term. DNA extracted from fetal tissues was
      subjected to PCR for detection of the egfp gene. Confocal microscopy and
      immunostaining were performed to determine the sites of transgene expression in
      the fetal organs. RESULTS: The egfp gene was detected in fetal blood and major
      organs (heart, liver, lung). The encoded protein was mainly produced in the
      endothelial cells of blood vessels in the fetal lungs. CONCLUSIONS: This is the
      first report on materno-fetal transfer of intradermally administered fusogenic
      liposome-plasmid DNA complexes and fetal expression of a transgene in primates.

PMID- 12221650
TI  - Transfectant mosaic spheroids: a new model for evaluation of tumour cell killing
      in targeted radiotherapy and experimental gene therapy.
AB  - BACKGROUND: We describe an in vitro tumour model for targeted radiotherapy and
      gene therapy that incorporates cell population heterogeneity. MATERIALS AND
      METHODS: Transfectant mosaic spheroids (TMS) and transfected mosaic monolayers
      (TMM) are composed of two cell populations derived from a single cell line. The
      cells of one population were transfected with the noradrenaline transporter gene
      (NAT), allowing active uptake of a radiolabelled targeting agent meta
      [131I]iodobenzylguanidine ([131I]MIBG); the other population of cells was derived
      from the same parent line and transfected with a marker gene - green fluorescent
      protein (GFP). After treatment with [131I]MIBG, cell kill was determined in TMM
      by clonogenic assay and in TMS by clonogenic assay and spheroid growth delay.
      RESULTS: We have used the TMS model to assess the 'radiological bystander effect'
      (radiation cross-fire) conferred by the beta-emitting radiopharmaceutical [131I]
      MIBG whose cellular uptake is facilitated by the transfected gene encoding NAT.
      We show that cell killing by [131I]MIBG in both TMS and TMM cultures increased in
      direct proportion to the fraction of NAT-transfected cells and that the degree of
      cell killing against fraction transfected was greater in TMS, suggestive of a
      greater bystander effect in the three-dimensional culture system. CONCLUSIONS:
      TMS provide a useful model for assessment of the effectiveness of targeted
      radiotherapy in combination with gene therapy when less than 100% of the target
      cell population is expressing the NAT transgene. Further, this novel model offers
      the unique opportunity to investigate radiation-induced bystander effects and
      their contribution to cell cytotoxicity in radiotherapy and other gene therapy
      applications.

PMID- 12221651
TI  - Development of the Korean version of Alzheimer's Disease Assessment Scale (ADAS
      K).
AB  - OBJECTIVE: The purpose of this study was the development of the Korean Version of
      Alzheimer's Disease Assessment Scale (ADAS-K). METHOD: ADAS-K was administrated
      to 84 AD patients as well as 105 non-demented control subjects. Three aspects of
      reliability were tested. To evaluate the validity of ADAS-K, discriminant
      validity and concurrent validity were tested. To evaluate the sensitivity of ADAS
      K to disease severity, all subjects, AD patients and control subjects, were
      grouped by CDR scale and their mean scores on ADAS-K were compared. RESULT: ADAS
      K demonstrated high levels of reliability. Mean ADAS-K scores for AD patients
      were significantly different from the control group (p < 0.01). Furthermore, ADAS
      K exhibited significant correlations with other tests and scales (range 0.45
      0.85, p < 0.01). In ROC curve analysis, ADAS-K displayed high diagnostic efficacy
      and the optimal cut-off point was selected between 18/19. ADAS-K was able to
      discriminate the degree of AD severity according to CDR classification. Our
      results suggested that ADAS-K-cog was sensitive to very mild AD. CONCLUSION: We
      demonstrated that ADAS-K is a reliable and valid instrument not only for AD
      diagnosis but also for evaluation of its severity.

PMID- 12221652
TI  - Out of sight out of mind? Support and information given to distant and near
      relatives of those with dementia.
AB  - OBJECTIVES: Increasing attention has been paid to the needs of family members
      caring for a person with dementia but little has been written about the impact on
      the wider family. This paper was intended to see whether the need for information
      would stretch to those relatives living far from the patient. METHOD: A case
      control study comparing two sets of relatives of community-dwelling probands in
      contact with secondary services and having a clinical diagnosis of dementia: one
      set of relatives living less than an hour away and another set living further
      away.The reported need for and source of information obtained by relatives was
      questioned using a specially designed questionnaire. Mini Mental State
      Examination (MMSE) and Clinical Dementia Ratings Scale were used with probands.
      RESULTS: Relatives living distantly from the person with dementia reported
      similar rates of subjective distress but were more often dissatisfied with
      information received. Distant relatives were also less likely to access
      information from books or lay societies. CONCLUSION: The impact of having a
      relative with dementia does not lessen with distance. The wider family need
      support and information as well as 'primary carers'. If the whole family is to be
      supported in their caring role, then clinicians and the lay societies need to
      widen their supportive net.

PMID- 12221653
TI  - Combined hearing and visual impairment and depression in a population aged 75
      years and older.
AB  - BACKGROUND: Depression is associated with both visual and hearing impairment.
      Little is known about the relationship between combined hearing and visual
      impairment and mood in this age group. The aim of this population-based study was
      to investigate the association between functional sensory impairment, especially
      combined sensory impairment and depressive symptoms and depression diagnosed
      according to the DSM-IV criteria. METHOD: The study group consisted of 470
      adults, population-based sample, aged 75 years or older. We used the Snellen eye
      charts with E-letters and reading charts to evaluate the functional visual
      acuity. The ability to conduct a face-to-face conversation, the hearing aid use
      and the self-reported hearing problems were used to assess the functional hearing
      acuity. Depression was identified with two different methods. A geriatrician
      interviewed the subjects and the DSM-IV checklist was used to determine whether
      they met the criteria for major depression. The Zung Depression Status Inventory
      (DSI) was used to identify depressive symptoms. The cut off points of 40/80 and
      48/80 in the DSI-score was used. RESULTS: Seventy-two persons (15%) of the study
      population had depression diagnosed according to the DSM-IV criteria. Twelve per
      cent of subjects in the Functional Hearing Impairment (FHI) group, twenty per
      cent in the Functional Visual Impairment (FVI) group, eighteen per cent in the
      Combined Sensory Impairment (CSI) group and fifteen per cent in the Adequate
      Sensory Function (ASF) group suffered major depression. The differences between
      these groups were insignificant. The occurrence rates of the DSI score equal or
      over 40 points was 50% in the FHI group, 53% in the FVI group, 70% in the CSI
      group and 45% in the ASF group. The difference between the ASF group and sensory
      impairment group including FHI, FVI and CSI groups was statistically significant
      (p = 0.03). CONCLUSIONS: Depressive symptoms, but not major depression, were
      common if elderly persons had combined sensory impairment.

PMID- 12221654
TI  - Are cognitively intact seniors with subjective memory loss more likely to develop
      dementia?
AB  - BACKGROUND: Subjective memory loss (SML) is common in elderly persons. It is not
      clear if SML predicts the development of dementia. OBJECTIVES: (1) to determine
      if SML in those with normal cognition predicts dementia or cognitive impairment
      without dementia (CIND); (2) to determine if an association is independent of the
      effect of age, gender and depressive symptoms. METHODS: Secondary analysis of the
      Manitoba Study of Health and Aging (MSHA), a population-based prospective study.
      Data were collected in 1991, and follow-up was done 5 years later. Community
      dwelling seniors sampled randomly from a population-based registry in the
      Canadian province of Manitoba, stratified on age and region. Only those scoring
      in the normal range of the Modified mini-mental state examination (3MS) were
      included. Predictor variables were self-reported memory loss, 3MS, Center for
      epidemiological studies-depression scale (CES-D), age, gender, and education.
      Outcomes were mortality and cognitive impairment five years later. RESULTS: In
      bivariate analyses, SML was associated with both death and dementia. In
      multivariate models, SML did not predict mortality. After adjusting for age,
      gender, and depressive symptoms, SML predicted dementia. However, after adjusting
      for baseline 3MS score, SML did not predict dementia. CONCLUSIONS: Memory
      complaints predict the development of dementia over five years, and clinicians
      should monitor these persons closely. However, the proportion of persons
      developing dementia was small, and SML alone is unlikely to be a useful clinical
      predictor of dementia.

PMID- 12221655
TI  - Alcoholism in older Korean men: prevalence, aetiology, and comorbidity with
      cognitive impairment and dementia in urban and rural communities.
AB  - BACKGROUND: Alcoholism in the elderly has received little research, particularly
      outside 'Western' cultures. OBJECTIVES: This study aimed to investigate the
      prevalence and aetiology of alcoholism, and its comorbidity with cognitive
      impairment and dementia in an older Korean population. METHODS: 1134 urban and
      rural community residents aged 65 or over were surveyed in Kwangju, South Korea.
      Alcoholism was identified by a culturally validated screening scale. RESULTS:
      Alcoholism was present in 16% of men and 2% of women. In men (n = 457),
      alcoholism was positively associated with manual occupation and negatively with
      religions encouraging temperance. In the urban sample, alcoholism was associated
      with higher education and with dementia. In the rural sample, it was associated
      with lower education and less strongly with dementia. CONCLUSIONS: The prevalence
      of alcoholism was high in this population. Associated factors and urban/rural
      differences reflect traditional attitudes toward drinking.

PMID- 12221656
TI  - Standard measures of executive function in predicting instrumental activities of
      daily living in older adults.
AB  - OBJECTIVE: The purpose of this study was to examine the ability of specific,
      commonly used neuropsychological tests of executive function to predict
      functional status among a group of elderly subjects. METHODS: Fifty study
      participants underwent a brief neuropsychological evaluation of executive
      functions and assessment of instrumental activities of daily living (IADL).
      RESULTS: A multiple stepwise regression analysis indicated that executive
      function tests accounted for 54% of the variance in functional status. An
      examination of the standardized regression coefficients revealed that Trail
      Making Test-Part B and the Wisconsin Card Sorting Test were the only two of the
      five executive function tests that significantly predicted functional status.
      These executive function measures contributed significantly to the prediction of
      functional status even after statistically controlling for age, sex, and
      education. CONCLUSION: Thus, the common clinical measures of executive function
      are useful in predicting functional status in older adults.

PMID- 12221657
TI  - Course of minimal dementia and predictors of outcome.
AB  - BACKGROUND: Previous studies have indicated that not all subjects who meet the
      CAMDEX criteria of 'minimal dementia' progress to dementia. In the present study,
      predictors of outcome in minimally demented subjects were tested. METHODS: Forty
      five subjects with minimal dementia who were participating in a population-based
      study were followed-up for on average 2.3 years. Variables tested as predictors
      of outcome were age, the apolipoprotein E (APOE) genotype, and the baseline
      scores on the MMSE, CAMCOG memory subscale, and fluency. Depression at baseline
      was tested as a predictor of reversible minimal dementia. RESULTS: At follow-up,
      minimal dementia turned out to be reversible in 11 subjects (24%), and persistent
      in ten subjects (22%). Twenty-four subjects (53%) had become demented. Predictors
      of outcome in multivariate analyses were age, score on the CAMCOG memory
      subscale, and the APOE genotype. Depression was not associated with reversible
      minimal dementia. CONCLUSIONS: Subjects who meet the CAMDEX criteria of minimal
      dementia form a heterogenous group with respect to clinical outcome. Age, the
      score on the CAMCOG memory subscale, and the APOE genotype can improve predictive
      accuracy in these subjects.

PMID- 12221658
TI  - One-year prevalence of death thoughts, suicide ideation and behaviours in an
      elderly population.
AB  - BACKGROUND: Suicidality is constituted by all those phenomena that are apparently
      positioned along a continuum, with the two extremes represented by death wishes
      and completed suicide. OBJECTIVES: The aim of this paper is to show the one-year
      prevalence of the phenomena constituting this possible continuum in the elderly
      population (aged 65 years and over) of a northern Italian city and to evaluate
      the relationship between some of these phenomena with psychological suffering.
      METHOD: Emotional feelings and suicidal thoughts have been investigated by an
      epidemiological survey conducted in a central quarter of that city. Data on
      attempted and completed suicide derived from the data bank of the Padua's WHO
      Collaborating Centre for Research and Training in Suicide Prevention that
      monitors these phenomena since 1989. RESULTS AND CONCLUSIONS: Results suggest the
      existence of some continuity in suicidal phenomena, where prevalence decreases
      from those of emotional/ideational nature to most extreme behaviour. Subjects
      presenting with more severe suicidal ideation were those also obtaining highest
      scores in a number of sub-scales of the Brief Symptom Inventory.

PMID- 12221659
TI  - Prevalence of dementia with Lewy bodies in an inpatient psychogeriatric
      population in Hong Kong Chinese.
AB  - OBJECTIVE: To find out the prevalence of dementia with Lewy bodies (DLB) in an
      inpatient psychogeriatric population in Hong Kong Chinese. METHOD: Clinical notes
      of all dementia patients admitted to an inpatient psychogeriatric unit between 1
      January and 31 December 2000 were reviewed to retrieve information on various
      subtypes of dementia that have been diagnosed prospectively using NINCDS-ARDRA,
      NINDS-AIREN, CDLB and DSM-IV by qualified senior psychogeriatricians. RESULT:
      There were only three cases of dementia with Lewy bodies out of 102 dementia
      inpatients, giving a prevalence rate of 2.9% over a two-year period. CONCLUSION:
      The prevalence rate of dementia with Lewy bodies is remarkably lower than figures
      reported in western studies. Further evaluation using better sampling frame and
      better-validated diagnostic gold standard is required. Ethnically related
      biological factors may be implicated to explain the preliminary low prevalence
      rate in Chinese population.

PMID- 12221660
TI  - Development and evaluation of a health-related quality of life questionnaire for
      the elderly with dementia in Japan.
AB  - OBJECTIVES: The purpose of this study was the development of the quality of life
      (QOL) questionnaire for dementia (QOL-D) in Japan. METHODS: We performed a
      questionnaire survey of QOL assessment in elderly patients with dementia in
      Japan, and developed QOL-D. RESULTS: The final version consists of only 31 items
      grouped into six response sets, each with its own scale. Reliability is good to
      excellent, and validity is, to some extent, established. The six domains of
      health-related QOL are divided into two groups. One is the positive and the other
      is the negative aspects of health-related QOL. The positive aspects have been
      shown to correlate positively with cognitive function and activities of daily
      living (ADL) score, whereas the negative aspects have not. The concept of QOL for
      elderly patients with dementia in Japan is similar to that in Western countries.
      CONCLUSION: We demonstrated that QOL-D is a reliable and valid instrument for QOL
      assessment in elderly patients with dementia in Japan.

PMID- 12221661
TI  - Homocysteine in neuropsychiatric disorders of the elderly.
AB  - OBJECTIVE: There is increasing interest in homocysteine as a risk factor for
      neuropsychiatric disorders such as stroke, dementia, depression and Parkinson's
      disease. This article reviews the current literature on the relationship between
      homocysteine and these disorders to ascertain if any clinical recommendations can
      be made. METHOD: A MEDLINE and EMBASE search was made for English language
      publications between 1966 and 2002 using the search terms 'Homocysteine' and
      'Stroke', 'Dementia', 'Vascular Dementia', 'Alzheimer's dementia', 'Cognition
      disorders or cognitive decline or memory disorders', 'Depression or depressive
      disorders' or 'Parkinson's disease'. In addition, individual articles were hand
      searched for relevant references. RESULTS: Cross-sectional studies consistently
      suggest that elevated homocysteine increases the risk of stroke, and may also
      increase the risk of leukoariosis, vascular dementia (VaD), cognitive impairment
      and Alzheimer's disease (AD). Longitudinal studies of homocysteine as a risk
      factor are few and inconsistently supportive of these associations. No
      intervention trials to determine the effect of lowering homocysteine levels have
      yet been published. The pathological mechanisms for homocysteine-mediated disease
      await complete elucidation. Mild hyperhomocysteinemia is common in the elderly
      population, and folate supplementation can decrease homocysteine levels.
      CONCLUSION: The epidemiological evidence for homocysteine as a risk factor for
      neuropsychiatric disease is an emerging area of great interest. Screening the
      population for hyperhomocysteinemia cannot be recommended at this stage, but
      individuals at increased risk of cerebrovascular disease or cognitive impairment
      should be investigated and treated for elevated homocysteine levels.

PMID- 12221662
TI  - Treatment of bipolar disorder in older adults.
AB  - BACKGROUND: It has been reported that 10% of all patients with bipolar disorder
      develop their illness after the age of 50, with bipolar disorder accounting for 5
      19% of mood disorder presentations in the elderly. There has been a growing
      awareness regarding the manifestation of bipolar disorder among older adults due
      to both changes in national demographics, and developing sophistication in the
      treatment of bipolar illness. A persistent problem in our understanding of
      management of late life bipolar disorder is the paucity of research and rigorous
      published studies on the psychopharmacology of this condition. OBJECTIVE: This
      paper reviews medication treatments, non-medication biological therapies, and
      psychosocial interventions for bipolar disorder in late life with a particular
      emphasis on age related modifiers of treatment. METHODS: Findings are based upon
      review of the current literature. RESULTS: There are multiple, significant gaps
      in our knowledge of bipolar disorder in late life which have important
      implications in the optimum treatment of elderly individuals with bipolar
      illness. CONCLUSION: There are a number of areas of needed future research in
      late life bipolar disorder.

PMID- 12221663
TI  - Psychotropics among the home-dwelling elderly--increasing trends.
AB  - OBJECTIVE: To assess the level of and changes in the use of psychotropics among
      the home-dwelling elderly in the 1990s. METHODS: A descriptive analysis based on
      data from two cross-sectional interview and health examination surveys of elderly
      persons aged 64 years or over conducted in Lieto, a typical semi-rural Finnish
      municipality, in 1990-91 and 1998-99. National prescription data were utilized to
      compare the use of psychotropics in the late 1990s by all Finnish home-dwelling
      elderly and the elderly in Lieto. In Lieto drug information was obtained from
      1131 persons in 1990-91 and from 1197 in 1998-99, and the mean age of the
      informants was 73 years in both surveys. The brand names of the prescription
      drugs (both irregular and regular medication) taken by each interviewee during
      seven days prior to the interview were recorded and categorized by the Anatomical
      Therapeutic Chemical (ATC) classification system. RESULTS: Every fourth person
      was taking at least one psychotropic drug in both surveys. Most users were on
      regular psychotropic medication. The use of hypnotics and antidepressants
      increased most during the study period. Polypharmacy and the use of psychotropics
      were most prevalent among those aged 85 years or over, with women predominating.
      Concomitant use of two or more psychotropics increased statistically
      significantly from 7% to 10% between the surveys. The young elderly, aged 64-71
      years, used cyclic antidepressants equally commonly in both surveys. None of the
      young elderly used new atypical antipsychotics in 1998-99. CONCLUSIONS:
      Psychotropics tend to be overprescribed and overused among the elderly, a group
      at the highest risk of adverse drug reactions. The tendency of prescribing for
      the elderly is not going in a better direction. New-generation psychotropics were
      not used. The need for long-standing use of psychotropics should be assessed
      regularly.

PMID- 12221664
TI  - Appeal against detention under the Mental Health Act 1983: relationship to age
      and incapacity.

PMID- 12221665
TI  - Factor V Leiden mutation carriership and venous thromboembolism in polycythemia
      vera and essential thrombocythemia.
AB  - Polycythemia Vera (PV) and Essential Thrombocythemia (ET) are chronic
      myeloproliferative disorders complicated by a high incidence of thrombotic
      complications. Extensive coagulation studies failed to demonstrate a consistent
      pattern of abnormalities associated with thrombosis. Recently, a poor
      anticoagulant response to activated protein C (APC), due to a mutation of factor
      V (FV Leiden), has been identified as the most frequent hereditary disorder
      associated with venous thrombophilia. We investigated in 304 patients with PV and
      ET whether the presence of FV Leiden could be a risk factor for thrombosis. FV
      Leiden was found in 14/304 patients (4.6%) and was associated with venous
      thromboembolism (VTE) occurred before and at diagnosis (5/27,16%, with a
      significant difference of prevalence in comparison of that observed in
      asymptomatic patients, 9/263, 3%, p = 0.003). Carriership of FV Leiden was
      associated with VTE relapse, with a prevalence of 3.6% in asymptomatic patients,
      6.9% in patients with a single episode of VTE and 18.1% in patients with
      recurrent VTE. The prevalence of FV Leiden in patients with and without arterial
      thrombosis was similar (5/79, 6% and 9/211, 4%, respectively, p = 0.337). This
      study indicates that the prevalence of the FV Leiden mutation in patients with PV
      and ET is comparable with that observed in the general population. FV Leiden
      mutation is a risk factor for VTE before and at time of diagnosis and for VTE
      recurrences. Screening for FV Leiden may be considered to identify PV and ET
      patients at higher risk of recurrences.

PMID- 12221666
TI  - Plasma chitotriosidase activity in patients with beta-thalassemia.
AB  - Variable increases in chitotriosidase levels have been reported in Italian
      patients with beta-thalassemia major and intermedia. We measured plasma
      chitotriosidase levels in Israeli patients with beta-thalassemia to ascertain its
      use as a universal marker of disease and/or response to therapy. Chitotriosidase
      levels in 39 adults (16-53 years; 30 with beta-thalassemia major, 9 with
      intermedia), and in 14 children (0.7-15 years; 12 with beta-thalassemia major, 2
      with intermedia) were compared with other measures of disease, such as ferritin,
      hemoglobin, liver function tests, and genotype. Plasma chitotriosidase levels
      were normal (0.37 +/- 0.04 mU/mL) in all children. Twelve adults (31%) had
      elevated levels (>1.33 mU/mL): 11 patients (37%) with thalassemia major and 1
      patient (11%) with thalassemia intermedia. A significant correlation was only
      found between plasma chitotriosidase levels and ferritin levels, and with mean
      number of transfusions per year. The patient with the highest chitotriosidase
      (1,440 nmol/mL/hr) had the highest ferritin (5,175 microg/L), required the most
      transfusions per year (40), and had abnormal liver tests. Normal chitotriosidase
      levels in the pediatric cohort and increased levels in only some adults may
      reflect status of iron overload in macrophages; thus there may be a role for
      monitoring chitotriosidase in patients with beta-thalassemia. Our results confirm
      results of the Italian cohort; however, in the latter, a more universal
      correlation was noted and chitotriosidase levels were much higher.

PMID- 12221667
TI  - Hyperhomocysteinemia and the MTHFR C677T mutation in Budd-Chiari syndrome.
AB  - Hyperhomocysteinemia (HH) is a factor that predisposes individuals to thrombosis,
      and the C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) is
      known to give increased plasma homocysteine. However, little is known about their
      roles in Budd-Chiari syndrome (BCS). This study evaluated the roles of HH and the
      MTHFR C677T mutation in patients with BCS. We compared 41 BCS patients with 80
      sex- and age-matched healthy controls. The mean plasma homocysteine level was
      significantly higher in patients with BCS (20.15 +/- 5.78 micromol/L) compared
      with normal controls (15.80 +/- 6.58 micromol/L), P < 0.01. HH (>19.5 micromol/L
      in men and >15.0 micromol/L in women) was detected in 15 (36.59%) patients and in
      14 (17.5%) controls (odds ratio [OR], 2.72; 95% confidence internal [CI], 1.17
      6.32). The prevalence of the mutated MTHFR 677TT genotype and the 677T allele in
      normal controls was 10.0% and 31.3%, respectively. The mutant 677T homozygotes
      and alleles were more frequent in patients with BCS than in controls (22.0% vs.
      10.0%, 0.025 < P < 0.05; 45.1% vs. 31.3%, 0.025 < P < 0.05). The relative risk of
      BCS among the carriers of 677TT was significantly increased (OR, 3.3; 95% CI, 1.1
      10.0). The mutant MTHFR heterozygous 677C/T carriers were not significantly
      increased in patients with BCS compared with controls (46.3% vs. < 2.5%, P >
      0.05). The relative risk OR of BCS among carriers of 677C/T was 1.6 (95% CI, 0.7
      3.6). This study suggests that both HH and the homozygous C677T mutation in the
      MTHFR gene are important risk factors of BCS.

PMID- 12221668
TI  - Acute myeloid leukemia with inv(16)(p13q22): involvement of cervical lymph nodes
      and tonsils is common and may be a negative prognostic sign.
AB  - Acute myeloid leukemia (AML) with inv(16)(p13q22) or the variant
      t(16;16)(p13;q22), is strongly associated with the FAB subtype M4Eo. A high
      incidence of CNS involvement was reported in the 1980s, but otherwise little is
      known about the pattern of extamedullary leukemia (EML) manifestations in this
      AML type. We have compiled clinical and cytogenetic data on 27 consecutive AML
      cases with inv(16)/t(16;16) from southern Sweden. In general, these AMLs
      displayed the clinical features that have previously been described as
      characteristic for this disease entity: low median age, hyperleukocytosis, M4Eo
      morphology, and a favorable prognosis. However, CNS leukemia was only seen in
      relapse in one patient diagnosed in 1980, whereas the most common EML
      manifestation in our series was lymphadenopathy (5/27, 19%), most often cervical
      with or without gross tonsillar enlargement. A review of previously published,
      clinically informative cases corroborates that lymphadenopathy, with preference
      for the cervical region, is the most common EML at diagnosis in inv(16)-positive
      AML (58/175, 33%). CNS leukemia, on the other hand, has been reported in only 17%
      of the cases, mostly in the relapse setting, with a diminishing frequency over
      time, possibly due to protective effects of high-dose cytarabine. Other reported
      EML sites include the scalp, ovaries, and the intestine. Cervicotonsillar EML was
      in our series associated with a shorter duration of first remission, (P < 0.05),
      and may hence prove to be an important clinical parameter when deciding treatment
      strategies in AML with inv(16)/t(16;16).

PMID- 12221669
TI  - Poor response to prednisolone of idiopathic thrombocytopenia with human T
      lymphotropic virus type I infection.
AB  - We describe the unique clinical characteristics of patients with idiopathic
      thrombocytopenic purpura (ITP) who are infected by human T-lymphotropic virus
      type I (HTLV-I). Thirty-seven patients with ITP were examined in the present
      study: 10 patients had HTLV-I infection, and the remaining 27 did not. The mean
      age of the group with HTLV-I infection was significantly older than that of the
      group without infection (57.8 +/- 14.0 and 42.4 +/- 20.1, P = 0.022). The
      difference in mean platelet counts at diagnosis between the two groups was not
      significant, 29 x 10(9)/L and 21 x 10(9)/L, respectively. The levels of platelet
      associated IgG, red blood cell count, white blood cell count, bone marrow cell
      count, and megakaryocyte count did not show any significant difference. Nine
      patients in the group with HTLV-I infection were treated with prednisolone (1
      mg/kg, daily oral). Only 3 of them responded to the therapy (one complete
      response [CR] and two partial responses [PR]). However, 17 of 22 patients not
      infected with HTLV-I were treated with prednisolone successfully: 14 patients
      achieved CR, and 3 patients achieved PR. There was a significant difference in
      response to prednisolone between the two groups (P = 0.034). Two patients with
      the infection and one patient without the infection achieved CR with splenectomy.
      These results suggest that HTLV-I infection may cause immune thrombocytopenia by
      a different mechanism than classical ITP; HTLV-I may modify the clinical features
      of ITP through an unknown immune pathway.

PMID- 12221670
TI  - Ticlopidine-induced aplastic anemia: two new case reports, review, and meta
      analysis of 55 additional cases.
AB  - Ticlopidine-induced aplastic anemia (TIAA) is considered very uncommon. We
      present two new cases, and we review 55 additional cases from the literature. The
      first case concerns a 70-year-old man who developed severe aplastic anemia 7
      weeks after treatment with 500 mg of ticlopidine daily. The patient sustained a
      severe septic episode, was treated with antibiotics and GM-CSF, and recovered the
      14(th) day after ticlopidine withdrawal. The second was an 82-year-old man
      receiving ticlopidine for 2 years when, during a febrile episode, he was found
      neutropenic with marrow aplasia. Ticlopidine withdrawal and treatment with
      antibiotics, transfusions, and G-CSF helped him to recover. When the data of the
      57 patients are evaluated, a reversible direct cytotoxic effect of ticlopidine on
      the pluripotent/bipotent hematopoietic progenitor stem cell is proposed. It is
      estimated that the real incidence if TIAA is higher, and many cases, initially
      presented as agranulocytosis +/- thrombocytopenia, might be true aplastic
      anemias, not proven by marrow aspiration or trephine biopsy. There is no
      effective monitoring to prevent this side effect. Recombinant growth factors
      appear not to help in shortening the neutropenic period.

PMID- 12221671
TI  - High-titer acquired factor V inhibitor responsive to corticosteroids and
      cyclophosphamide in a patient with two malignant tumors.
AB  - We report a 79-year-old man with two simultaneous malignant tumors (buccal
      epidermoid carcinoma and prostatic adenocarcinoma) who developed a severe
      bleeding complication at the site of the buccal tumor as well as a massive
      cerebral hematoma after a skull trauma. Laboratory findings showed the presence
      of a high-titer specific factor V inhibitor. The patient failed to respond to
      intravenous immunoglobulins, but both clinical and laboratory improvement was
      obtained after treatment with corticosteroids and cyclophosphamide.

PMID- 12221672
TI  - A successful second unrelated BMT (UBMT) from a different unrelated donor to
      treat ALL that relapsed after the initial UBMT.
AB  - A 26-year-old male with acute lymphoblastic leukemia (ALL) in its second complete
      remission received an unrelated bone marrow transplantation (UBMT) following
      cyclophosphamide plus total body irradiation conditioning. The patient relapsed 7
      months after the BMT. He received a second UBMT from a different donor 15 months
      after the initial UBMT. Conditioning for the second UBMT consisted of busulphan,
      melphalan, and anti-thymocyte globulin. The regimen was well tolerated, and
      engraftment was achieved. Both acute and chronic graft-versus-host diseases
      occurred but were successfully controlled with immunosuppressive drugs. He is
      alive and disease-free 29 months after the second UBMT. This is the first report
      of a successful second UBMT for ALL that had relapsed after the first UBMT and
      for which a different donor was used.

PMID- 12221673
TI  - Resolution of psoriasis following allogeneic bone marrow transplantation for
      chronic myelogenous leukemia: case report and review of the literature.
AB  - We describe a case of a 49-year-old man with chronic myelogenous leukemia (CML)
      whose coincidental psoriasis resolved following allogeneic bone marrow
      transplantation (BMT). The patient had suffered from psoriasis for 20 years and
      was treated with corticosteroid ointment. He was diagnosed as having CML in 1998,
      and his psoriasis deteriorated following interferon therapy. In March 1999, he
      received a BMT from an HLA-identical sister after undergoing a conditioning
      regimen involving busulfan, cytosine arabinoside, and cyclophosphamide.
      Prophylaxis of acute graft-versus-host disease was done using short-term
      methotrexate and cyclosporin A. His psoriasis improved immediately and
      disappeared completely on day 70 after BMT. For 2.5 years, his CML remains in
      remission and he is free of psoriasis without undergoing immunosuppressive
      therapy. This case suggests the potential benefits of the treatment of immune
      mediated diseases with allogeneic BMT.

PMID- 12221674
TI  - Induction of fetal hemoglobin synthesis by valproate: modulation of MAP kinase
      pathways.
AB  - Valproate has been found to stimulate fetal hemoglobin (HbF) synthesis in
      patients with sickle cell disease. In accordance with these clinical
      observations, we found a moderate induction of HbF synthesis in K562 erythroid
      cells in vitro. Investigation of the role of the mitogen-activated protein kinase
      (MAPK) pathways by Western blot analysis and use of specific kinase inhibitors
      suggests that inhibition of ERK pathway and activation of the p38 pathway may
      contribute to the HbF-inducing activity of valproate.

PMID- 12221675
TI  - Acute myocardial infarction as the presenting symptom of acute myeloblastic
      leukemia with extreme hyperleukocytosis.
AB  - This case report deals with an unusual leukostatic complication in a 56-year-old
      woman with acute myeloblastic leukemia (AML) and extreme hyperleukocytosis (316 x
      10(9)/L) who presented with acute myocardial infarction (MI). After leukopheresis
      the patient achieved hemodynamic stabilization and rapid neurologic recovery of
      encephalopathy that had also developed after the infarction. Considering the
      central role of WBC in the remodeling of post MI myocardial tissue, it was
      obvious that administration of chemotherapy with its subsequent inevitable
      pancytopenia could impose an increased risk for further cardiac complications
      including myocardial rupture. Nevertheless, cytarabine-based induction
      chemotherapy was initiated 3 days after admission, and she achieved prolonged
      complete remission. Coronary angiography disclosed segmental atherosclerosis, but
      the only significant obstruction was in the right coronary artery. The patient
      died with relapsed leukemia 7 years later without recurrence of any cardiac
      symptoms or signs. Autopsy disclosed segmental coronary atherosclerosis involving
      the LAD (60% obstruction), suggesting that atherosclerosis was a predisposing
      risk factor. Additional compromise to blood perfusion due to leukostasis had led
      to this unusual complication of AML involving a major vessel. This is the first
      documented case of leukostasis causing coronary artery occlusion as well as the
      first report of successful induction chemotherapy for AML during a myocardial
      infarction.

PMID- 12221676
TI  - Venous limb gangrene during overlapping therapy with warfarin and a direct
      thrombin inhibitor for immune heparin-induced thrombocytopenia.
AB  - We report two patients with deep-vein thrombosis complicating immune heparin
      induced thrombocytopenia who developed venous limb gangrene during overlapping
      therapy with a direct thrombin inhibitor (lepirudin or argatroban) and warfarin.
      In both patients, therapy with the direct thrombin inhibitor was interrupted
      during persisting severe athrombocytopenia while warfarin administration
      continued. Both patients exhibited the typical feature of a supratherapeutic
      international normalized ratio (INRs, 5.9 and 7.3) that has been linked
      previously with warfarin-associated venous limb gangrene. These data suggest that
      warfarin anticoagulation be postponed in patients with acute heparin-induced
      thrombocytopenia until substantial recovery of the platelet count has occurred.

PMID- 12221677
TI  - No effect of acenocoumarol therapy on levels of endothelial activation markers in
      sickle cell disease.
AB  - Sickle cell patients are characterized by a chronic inflammatory and
      hypercoagulable state, depicted by elevated levels of pro-inflammatory cytokines,
      endothelial adhesion molecules, and elevated markers of thrombin generation. We
      set out to determine whether anticoagulation with a coumadin derivative reduces
      inflammation in sickle cell disease. Therefore, serum levels of NFkappaB
      regulated endothelial adhesion molecule soluble vascular cell adhesion molecule-1
      and serum levels of non-NFkappaB-dependent markers of endothelial activation
      (soluble cellular fibronectin and von Willebrand factor antigen) were compared
      during treatment with acenocoumarol (INR 1.6-2.0) and placebo. No effect on
      circulating levels of the measured parameters was observed during treatment with
      acenocoumarol as compared to placebo. In the targeted INR range, anticoagulation
      of sickle cell patients with acenocoumarol does not seem to reduce endothelial
      activation.

PMID- 12221678
TI  - Rapid confirmation of Southeast Asian and Filipino alpha-thalassemia genotypes
      from newborn screening specimens.
AB  - Alpha(+)-thalassemia (-alpha) is prevalent throughout tropical and subtropical
      regions of world, whereas alpha(0)-thalassemia (--) occurs at higher frequency in
      Southeast Asia. Homozygosity for the alpha(0)-thalassemia deletion (--/--) is a
      serious health problem in Southeast Asia and the Philippines and is responsible
      for the majority of hydrops fetalis in this region. Asian immigration in United
      States has impacted the demography of genetic disease in U.S. As Asians comprise
      of 10% of all California births and represent a population at highest risk for
      alpha(0)-thalassemia, we developed a rapid and efficient PCR approach to detect
      the common alpha(0)-thalassemia deletions in Southeast Asians and Filipinos using
      newborn screening specimen.

PMID- 12221679
TI  - A post-menopausal woman with anuria and uterus bulk: the spectrum of estrogen
      induced TTP/HUS.

PMID- 12221680
TI  - Central nervous system relapse in acute promyelocytic leukemia.

PMID- 12221682
TI  - ATRA syndrome with extensive organ infiltration.

PMID- 12221681
TI  - Abrogation of macrocytosis in pernicious anemia by beta-thalassemia does not mask
      the diagnosis of vitamin B12 deficiency.

PMID- 12221683
TI  - Long-term disease-free survival in a primary plasma cell leukemia treated by VAD,
      autologous PBSC transplantation, and IFN-alpha.

PMID- 12221684
TI  - Congenital dyserythropoietic anemia type II with a positive sucrose hemolysis
      test.

PMID- 12221685
TI  - Enhanced response to basiliximab in a patient with aplastic anemia after
      treatment with standard immunosuppression.

PMID- 12221686
TI  - all-trans-Retinoic acid in the treatment of Kimura's disease.

PMID- 12221687
TI  - Reflections of an editorial assistant.

PMID- 12221688
TI  - Psychometric characteristics of dyspnea descriptor ratings in emergency
      department patients with exacerbated chronic obstructive pulmonary disease.
AB  - The purpose of this study was to evaluate the reliability, content validity, and
      factor structure of dyspnea sensory quality descriptor ratings in emergency
      department (ED) patients with exacerbated chronic obstructive pulmonary disease
      (COPD). During an ED visit 104 patients with COPD rated the intensity of 16
      dyspnea sensory quality descriptors (numerical ratings of 0-10) in relation to
      how they felt when they decided to come to the ED (Decision) and 1 week before
      the visit. Content validity of 15 descriptors was supported. Factor analysis of
      Decision ratings resulted in seven descriptors and three factors (alpha=.88; 74%
      common variance): Smothering/Suffocating/Hunger for air (alpha=.87); Effort/Work
      (alpha=.87); and Tight/Constricted (alpha=.74). Results indicate that the
      intensity of sensory quality descriptors can be measured reliably in COPD
      patients during an exacerbation of COPD. The initial descriptor list of
      descriptors could be cut by more than half while retaining satisfactory
      psychometric properties.

PMID- 12221689
TI  - Early discharge following abdominal aortic aneurysm repair: Impact on patients
      and caregivers.
AB  - Although early discharge is common place, little is known about its impact after
      abdominal aortic aneurysm (AAA) surgery. We sought to prospectively describe
      patient outcomes and caregiving experience after early discharge following
      elective AAA repair using a standard or endovascular grafting system (EGS)
      procedure. Fifty-one patients (Standard, n=25; EGS, n=26) completed
      questionnaires on symptoms and health-related quality of life (HRQoL) while
      hospitalized and 1, 4, and 8 weeks after discharge. Data were also obtained from
      caregivers. HRQoL decreased at Week 1 in both groups but returned to near
      baseline by Week 8. Standard AAA patients experienced more symptoms and activity
      limitations, but these were concentrated in Week 1. Most caregivers were positive
      about caregiving and required no additional resources. Findings suggest that most
      patients who undergo early discharge following elective AAA surgery experience
      few problems. Those problems that occur concentrate in the week following
      discharge, suggesting the need for closer monitoring at this time.

PMID- 12221690
TI  - Home environmental modification strategies used by caregivers of elders.
AB  - Although several definitions and categorizations of home environmental
      modification strategies exist, previous researchers have not addressed whether
      the conceptualizations developed by clinicians and researchers match the way
      families think about how they modify the home environment in order to provide
      care to frail elders. The aim of the analysis reported here was to describe, from
      the family's perspective, the home environmental modification strategies that
      they use. Twenty-four caregivers of community-dwelling elders with a variety of
      impairments were interviewed. Seventeen families provided guided tours of the
      elder's home and allowed selected observation of some caregiving activities.
      Forty-four modification strategies were identified and categorized into one of
      seven home environmental modification purposes: organizing the home,
      supplementing the elder's function, structuring the elder's day, protecting the
      elder, working around limitations or deficits in the home environment, enriching
      the home environment, and transitioning to a new home setting. More research is
      needed on the processes families use to generate and refine the home
      environmental modification strategies identified in this study.

PMID- 12221691
TI  - African Americans with cancer: the relationships among self-esteem, locus of
      control, and health perception.
AB  - The purpose of this study was to describe and examine the relationships among
      self-esteem, locus of control, and perceived health status in African Americans
      with cancer and to identify predictors of perceived health status. A convenience
      sample of 95 oncology outpatients at two large medical facilities completed the
      Tennessee Self-Concept Scale, the Multidimensional Health Locus of Control Scale,
      and the Cantril Ladder, a measurement of perceived health. In an audiotaped
      interview two open-ended questions were used to clarify participants' Cantril
      Ladder scores. A significant positive relationship was discovered between self
      esteem and powerful others health locus of control (p <.05). Participants tended
      to view God as the Powerful Other capable of influencing their health and well
      being. Self-esteem and an internal health locus of control were found to account
      for 23% of the perceived variance in health status. In addition, interview data
      indicated that participants with normal to high levels of self-esteem and an
      internal health locus of control perceived their state of health and well-being
      positively.

PMID- 12221692
TI  - Stress-related influences on blood pressure in African American women.
AB  - The relationship of blood pressure status to three stress-related variables,
      anger, coping resources, and strain, was evaluated in 90 African American women.
      The majority of the participants (57%) were normotensive, 32% of the participants
      reported current use of hypertensive medication, and an additional 16% had a mean
      blood pressure greater than 140/90 mmHg but were not on hypertensive therapy.
      From an analysis using ANCOVA, participants in the latter group were found to
      have significantly higher scores on rational-cognitive coping resources,
      controlling for age, waist/hip ratio, and pack-years. No significant differences
      among the blood pressure groups were found in anger or personal strain. Fostering
      rational-cognitive coping skills, which represent the ability to problem-solve
      effectively and to set priorities, may be beneficial for African American women
      and should be evaluated further in a larger sample.

PMID- 12221693
TI  - Infant and caregiving factors affecting weight-for-age and motor development of
      full-term and premature infants at 1 year post-term.
AB  - Guided by a theoretical process model, we examined direct and indirect effects of
      infants' biologic condition and experience, the caregiving environment, and
      caloric intake variables on two outcomes, weight-for-age and motor development,
      for 52 full-term and 47 premature infants at 12 months post-term age. For full
      term infants, birth weight and infant expression of positive affect and behavior
      during feeding had predicted positive direct effects on weight-for-age. Infant
      regulation of negative affect and behavior had an unexpected negative effect on
      this outcome. For premature infants, severity of acute illness, mother's
      regulation of negative affect and feeding behavior, and caloric intake affected
      weight-for-age in unpredicted directions. Caregiving variables had indirect
      effects, through caloric intake, on both outcomes only for premature infants. The
      findings suggest the theoretical process model differs for premature infants and
      full-term infants, both in the contributing variables and in the processes of
      effects.

PMID- 12221694
TI  - Methodological concerns for non-Hispanic investigators conducting research with
      Hispanic Americans.
AB  - The fastest-growing ethnic population in the United States, Hispanic Americans
      are underrepresented in health care research because of an insufficient number of
      Hispanic American researchers, study teams without Spanish-speaking members, a
      lack of Spanish-language instruments, and investigator ignorance about cultural
      differences. Culturally insensitive research produces biased results that can
      inaccurately represent Hispanic Americans. The purpose of this article is to
      discuss methodological concerns when conducting research with Hispanic Americans
      including: instrument response format, translation issues, population-related
      extraneous variables, and response tendencies that can influence results.

PMID- 12221696
TI  - In vivo biocompatibility testing of peek polymer for a spinal implant system: a
      study in rabbits.
AB  - We are developing a new spinal implant system (SIS) without fusion (bone graft).
      This SIS is made from two materials, metal and polyetheretherketone (PEEK)
      polymer. The Food and Drug Administration recommended testing in vivo, in an
      animal model, whether the PEEK polymer could be used in a SIS without any harm of
      wear debris to the nervous tissue (spinal cord and nerve roots). The objective
      was to evaluate the biological response of the spinal cord and nerve roots (dura
      mater) to PEEK polymer particles. Twenty-four female New Zealand white rabbits
      were used. The rabbits were divided into three groups: test (n = 12), control (n
      = 9), and sham (n = 3). During the surgery, the test group received the PEEK
      particle injections (5 x 10(7) particles per site, lumbar and thoracic), while
      the control group received only the vehicle (0.9% saline solution). The sham
      group had the same surgical approach without injection. In each group, the
      rabbits were euthanized at 1, 4, and 12 weeks postsurgery. The macroscopic and
      semiquantitative histologic analyses of the spinal cords (dura mater) showed
      normal vascularization and particle adherence to the connective tissue especially
      at the injection sites. Neither necrosis nor swelling of the dura mater and nerve
      roots was observed. The PEEK polymer is harmless to the spinal cord; thus it
      might be used as component in the spinal implant system.

PMID- 12221697
TI  - Growth of connective tissue progenitor cells on microtextured
      polydimethylsiloxane surfaces.
AB  - Growth of human connective tissue progenitor cells (CTPs) was characterized on
      smooth and microtextured polydimethylsiloxane (PDMS) surfaces. Human bone-marrow
      derived cells were cultured for 9 days under conditions promoting osteoblastic
      differentiation on smooth PDMS surfaces and on PDMS post microtextures that were
      6 microm high and 5, 10, 20, and 40 microm in diameter, respectively. Glass
      tissue-culture dishes were used as controls. The number of viable cells was
      determined, and an alkaline phosphatase stain was used as a marker for
      osteoblastic phenotype. CTPs attached, proliferated, and differentiated on all
      surfaces. Cells on the smooth PDMS and control surfaces spread and proliferated
      as colonies in proximity to other cells and migrated in random directions, with
      cell process lengths of up to 80 microm. In contrast, cells on the PDMS post
      microtextures grew as sparsely distributed networks of cells, with processes,
      occasionally up to 300 microm, that appeared to interact with the posts. Cell
      counts revealed that there were fewer (50%) CTPs on the smooth PDMS surface than
      were on the glass control surfaces. However, there were consistently more (>144%)
      CTPs on the PDMS post textures than on the controls. In particular, the 10-microm
      in-diameter posts (268%) exhibited a significantly (p < 0.05) greater cell number
      than did the smooth PDMS.

PMID- 12221698
TI  - Biostability of electrically conductive polyester fabrics: an in vitro study.
AB  - The biostability of a series of polypyrrole (PPy)-coated polyester fabrics was
      investigated in an in vitro model. PPy-coated sample fabrics were incubated in
      saline at 37 degrees C for 1 and 2 weeks. After each period of incubation, the
      surface electrical resistivity of the sample fabrics was measured to monitor the
      changes caused by the incubation. Redoping was then performed by immersing the
      sample fabrics in a 1N HCl solution at room temperature for 30 min, which was
      followed by another measurement of the surface resistivity. The surface
      morphology of the sample fabrics was observed by scanning electron microscopy.
      The surface chemical composition of the fabrics and the oxidation of nitrogen in
      PPy were measured with X-ray photoelectron spectroscopy. The surface electrical
      resistivity of the PPy-coated fabrics was found to increase with the progress of
      incubation, which was mainly caused by dedoping and uptake of oxygen. This
      increase was nonlinear and accelerated with time. The surface resistivity of most
      of the samples was retained in the range of 10(3)-10(4) Omega/square after 1 week
      of incubation, which was considered suitable for short-term electrical
      stimulation applications. Physical deterioration represented by the cracking and
      delamination of the PPy coating was occasionally observed on the sample fabrics
      showing the most significant increase of resistivity. Further improvement of the
      stability of conductivity is highly desirable.

PMID- 12221699
TI  - In vitro evaluation of phosphonylated low-density polyethylene for vascular
      applications.
AB  - The use of catheters for vascular applications is often complicated by the
      development of friction between the catheter material and the vessel wall, which
      leads to endothelial cell removal and intimal lesions. Phosphonylation, a
      chemical surface treatment, has been proposed as a means of increasing the
      hydrophilicity of low-density polyethylene (LDPE), a commonly used catheter
      material, in efforts to impart lubricity to the material and reduce vascular
      tissue damage. In an in vitro tribological study, phosphonylated LDPE produced a
      lower coefficient of friction and allowed greater retention of endothelial cells
      on vessels as compared to untreated LDPE when the materials were reciprocated
      against normal porcine aorta. Chemical characterizations of the LDPE before and
      after friction testing involving Fourier transform infrared and energy-dispersive
      X-ray (EDX) confirmed the phosphorus content on phosphonylated LDPE. Election
      spectroscopy for chemical analysis (ESCA) and atomic force micrscope (AFM)
      analyses verified that proteins initially adsorb to both the phosphonylated and
      untreated LDPE surfaces and that the proteins interfere with water to lubricate
      the surfaces. However, with repeated friction, proteins are removed from the
      surface and hydrophilicity, as imparted by phosphonylation, becomes a principal
      factor in the lubrication process.

PMID- 12221700
TI  - Pharmacological studies of RGTA(11), a heparan sulfate mimetic polymer, efficient
      on muscle regeneration.
AB  - RGTA is a family of chemically modified polymers that have been engineered to
      mimic the properties of heparan sulfates towards heparin binding growth factors.
      In vivo, RGTA stimulated tissue repair and protection when injected at the site
      of an injury. These properties have been reported in various models, suggesting a
      potential interest for therapeutic uses as a general tissue repair agent. We have
      focused our interest on RGTA(11), a dextran derivative that was shown to enhance,
      after a unique and local administration, muscle regeneration after total
      crushing. We first show that a single RGTA(11) systemic administration can be as
      efficient as a local injection for stimulating muscle regeneration. Using an H(3)
      labeled RGTA(11) we have measured some pharmacokinetic parameters. Distribution
      volume was 51.81 mL, clearance was about 2 mL/min, and half-life was 94 min,
      giving a total elimination time of 11 h. We also demonstrate that RGTA(11)
      remains detectable in the body only after tissue injury. It was detected by
      autoradiography in the crushed muscle just after injury and remained at least for
      a week. These results provide a rational explanation for the long lasting effect
      of a single local or systemic injection of RGTA.

PMID- 12221701
TI  - Surface engineering of poly(D,L-lactic acid) by entrapment of chitosan-based
      derivatives for the promotion of chondrogenesis.
AB  - Chitosan and chitosan-amino acid derivatives were explored to engineer poly(D,L
      lactic acid) (PDL-LA) as an extracellular matrix-like surface to promote cell
      adhesion and growth. Four kinds of chitosan-amino acid derivatives were prepared
      to mimic the carbohydrate moieties of cell matrix glycoprotein. The chitosan
      amino acid derivatives were characterized by using Fourier transform infrared and
      ultraviolet spectra. The amino acid content on chitosan-amino acid derivatives
      was determined by using a ninhydrin-ultraviolet method. A new strategy,
      entrapment, was therefore used to modify the PDL-LA membrane with chitosan and
      chitosan-amino acid derivatives. The results of X-ray photoelectron spectroscopy,
      attenuated total reflectance-Fourier transform infrared, and contact angle
      confirmed that a stable thin film of chitosan and its derivatives can be
      entrapped on the surface of the PDL-LA membrane. From the results of chondrocyte
      cytocompatibility, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide] assays, and cell morphology, the chitosan-amino acid derivative modified
      PDL-LA membranes were shown to promote chondrogenesis. The novel surface
      treatment method combines the good mechanical property of PDL-LA with the good
      cytocompatibility of chitosan derivatives, which may have potential for tissue
      engineering.

PMID- 12221702
TI  - Oxidation-induced dynamic changes in morphology reflected on freeze-fractured
      surface of gamma-irradiated ultra-high molecular weight polyethylene components.
AB  - Oxidative degradation of ultra-high molecular weight polyethylene (UHMWPE)
      attributed to sterilization by gamma-radiation in the presence of air has been
      cited as one of the major causes of premature wear in total joint arthroplasty.
      For example, in retrieved UHMWPE tibial bearings, not only adhesive and abrasive
      wear, but also fatigue wear characterized by delamination and fracture is
      frequently observed. In this study, we examined the effects of gamma radiation on
      the microstructural morphology of UHMWPE tibial bearings, and propose a severe
      fatigue wear mechanism. Scanning electron microscopic observations were conducted
      on freeze-fractured surface of retrieved UHMWPE components that had been
      sterilized with gamma radiation in air before implantation, unused components
      that had been stored on the shelf for several years (5-11) after sterilization,
      and disc specimens given an accelerated aging protocol after gamma radiation.
      Scanning electron microscopic observations showed that the freeze-fractured
      surface of these components had a double layer, which was bordered below the
      surface. A closer observation of the subsurface layer below the border revealed
      an extremely rough and porous honeycomb-like structure. Fourier transform
      infrared analysis demonstrated that the honeycomb-like region in the subsurface
      had a high oxidation level. The internal morphology of oxidized UHMWPE was
      classified into four categories based on the level of the oxidation. According to
      these results, the morphological changes with oxidative degradation of gamma
      irradiated UHMWPEs in the presence of air could consistently be explained as the
      result of major chemical and physical changes such as increased crystallinity,
      elevated density, and reduced mechanical strength. We relate the morphological
      changes caused by oxidative degradation in the subsurface to the location of the
      origin of fatigue wear in total knee joints.

PMID- 12221703
TI  - Biocompatibility of dense hydroxyapatite prepared using an SPS process.
AB  - In the present study, the preparation of dense hydroxyapatite (HAp) materials at
      relative low temperatures using a spark plasma sintering was carried out. The
      bioactivity of HAp samples prepared by a spark plasma sintering method was
      investigated by in vitro tests and compared with HAp obtained by a conventional
      hot-pressing method. No growth of bone-like HAp crystals on surface of HAp
      sintered by a conventional hot-pressing method at 1200 degrees C was observed
      after immersion in a simulated body fluid (SBF) for 2 days. However, many large
      bone-like HAp crystals were observed on the surface of HAp samples prepared by a
      spark plasma sintering at 1200 degrees C after 2 days in the SBF immersion test.
      Especially, the negatively charged surface of the HAp samples prepared by spark
      plasma sintering was covered with larger HAp crystals compared with the
      positively charged surface. The electric poling of HAp was measured using a
      thermally simulated current technique. This rapid growth of bone-like HAp
      crystals of the HAp samples made by spark plasma sintering was believed to be
      related with the OH(-) and/or Ca(2(+) ) ion deficiency at the grain boundaries of
      the HAp matrix grains as well as a small electric poling effect resulting during
      the spark plasma sintering process.

PMID- 12221704
TI  - Cell adhesion on poly(propylene fumarate-co-ethylene glycol) hydrogels.
AB  - We synthesized poly(propylene fumarate-co-ethylene glycol) block copolymers [P(PF
      co-EG)] that were crosslinked to form hydrogels and investigated the effect of
      copolymer composition on cell adhesion to the hydrogels. These copolymers were
      water soluble when the molar ratio of ethylene glycol repeating unit to propylene
      fumarate repeating unit was higher than 4.4. The water content of swollen
      hydrogels increased from 29 to 63% and the water contact angle decreased from 38
      to 21 degrees as the molar ratio increased from 0.6 to 4.4. No significant change
      in either property was observed for ratios higher than 4.4. In a cell adhesion
      assay under serum-free conditions, the number of adherent platelets and smooth
      muscle cells decreased from 21 to 2% and from 78 to 20% of the initial seeding
      density, respectively, as the molar ratio increased from 0.6 to 7.8. Adherent
      smooth muscle cells did not spread on the hydrogels of the compositions tested.
      Adherent platelets did not show any filopodia. These results suggest that the
      hydrophilicity of P(PF-co-EG) hydrogels is one of the factors affecting cell
      adhesion, and that copolymer modification may be required for enhancing cell
      adhesion for an application involving the copolymers as in situ crosslinkable
      cell carriers.

PMID- 12221705
TI  - Adsorption/desorption phenomena on pure and Teflon AF-coated titania surfaces
      studied by dynamic contact angle analysis.
AB  - As a result of inflammatory processes, plaque formation on dental titanium
      implants often leads to clinically pathogenic situations. This special biofilm
      formation on (bio)materials in contact with saliva is initiated by ionic and
      protein interactions. In this interfacial process, albumin becomes a main
      constituent of dental pellicle. Interfacial reactions change the surface
      characteristics. They determine the following steps of macromolecular adsorption
      and bacterial adhesion. This work focuses on the dynamic contact angle analysis
      (DCA), which is a tool for online measurements of dynamic changes of wettability
      without disturbing the interface during detection. Repeatability of the DCA
      method has been assessed according to the Bland and Altman method. The kinetics
      and equilibrium data of shifts in the wetting tension hysteresis indicate ionic
      influences at the titanium/bovine serum albumin (BSA) interface: the Ca-mediated
      increase of the BSA adsorption on titanium and the adsorption maximum at the
      isoelectric point (IEP) of BSA. Ti was surface modified by Teflon AF polymeric
      coatings. The result of the assessment gives reason to consider Teflon AF as a
      reference material for DCA repeatability studies. This surface modification
      caused drastic changes in the dynamic interfacial reactions. Shifts in the
      wetting tensions during DCA adsorption-desorption experiments clearly
      demonstrated the partially irreversible adsorption of BSA on Teflon AF. In
      contrast, reversible adsorption behavior was detected on pure Ti surfaces. These
      findings strengthen the hypothesis that the analysis of dynamic changes in
      wetting tension and wetting tension hysteresis is a sensitive analytical method
      for the detection of dynamic interfacial changes at biomaterial/biosystem
      interfaces during the initial steps of biofilm formation.

PMID- 12221706
TI  - Micropattern formation of apatite by combination of a biomimetic process and
      transcription of resist pattern.
AB  - Two kinds of methods combining a biomimetic process and transcription of resist
      pattern were conducted to form an apatite micropattern. For method 1, apatite
      nuclei were formed on a resist pattern printed substrate by setting it in contact
      with CaO-SiO(2)-based glass in a simulated body fluid (SBF) with inorganic ion
      concentrations nearly equal to those of human blood plasma. Next, apatite was
      grown from the nuclei by soaking the substrate in an aqueous solution with ion
      concentrations 1.5 times those of SBF (1.5 SBF). Then, the resist material was
      dissolved off by organic solvent with the apatite just formed on it. Apatite
      micropattern transcribing the resist pattern was obtained. For method 2, apatite
      nuclei were formed on a resist pattern printed substrate by setting it in contact
      with CaO-SiO(2)-based glass in SBF. Next, the resist material was dissolved off
      with the apatite nuclei just formed on it. Then, the substrate was soaked in 1.5
      SBF to grow the remaining nuclei and an apatite micropattern transcribing the
      resist pattern was obtained. For both methods, minute apatite patterns with
      various shapes as straight lines, bending lines, and blocks were clearly formed.
      The minimum line width of the obtained pattern was 2 microm. These methods are
      promising for producing multifunctional materials with bioaffinity.

PMID- 12221707
TI  - In vivo evaluation of hydroxyapatite foams.
AB  - Hydroxyapatite (HA) is widely applied as bone graft material due to its
      osteoconductive potential and well-established biocompatibility. In this work,
      macroporous hydroxyapatite structures made through foaming of aqueous suspensions
      and gelcasting were tested for in vivo osteointegration. These foams are composed
      of a three-dimensional array of spherical pores with diameters of approximately
      100-500 microm, interconnected by windows of smaller size in the range of 30-120
      microm. The HA foams were implanted in the tibia of albino New Zealand rabbits
      and removed after a period of 8 weeks. Histological analysis revealed that the
      pores in the foams were partially or completely filled progressively with mature
      new bone tissue and osteoid after the implanted period. No immune or inflammatory
      reactions were detected. The high osteoconductive potential of the HA foams
      provides a potential structure for use as bone substitute in orthopedic, oral,
      and cranio-maxillofacial reconstructive surgery, and as dento-alveolar implants.

PMID- 12221708
TI  - Preparation of calcium aluminate cement for hard tissue repair: effects of
      lithium fluoride and maleic acid on setting behavior, compressive strength, and
      biocompatibility.
AB  - We investigated lithium fluoride (LiF) and maleic acid (MA) containing calcium
      aluminate cement (CAC) for hard tissue repair. The objective of this study is to
      estimate the addition effects of LiF and MA on setting behavior, compressive
      strength, and biocompatibility of CAC and to find the most compatible composition
      of LiF and MA for using CAC as a new bone cement. The CAC was composed mainly of
      CaO. Al(2)O(3). Samples of LiF and MA containing CAC were formed along with
      recording of setting time and peak temperature and then set cement was analyzed
      by X-ray diffraction (XRD). Agar diffusion test, tetrazolium bromide (MTT) assay,
      and hemolysis test were used to detect initial in vitro biocompatibility of LiF
      and MA containing CAC. It was revealed from the results that LiF shortened
      setting time and decreased compressive strength, whereas MA delayed setting time
      and increased compressive strength. However, LiF and MA showed no or little
      influence on maximum temperature of CAC. CAC containing 0.5 g of LiF and 8.75 g
      of MA showed the highest compressive strength (111.64 +/- 7.74 MPa) across all
      the experimental compositions. The CACs containing 0.5 g of LiF/8.75 g of MA and
      1.01 g LiF/8.75 g of MA had no cytotoxicity and hemolysis. In this study, CAC
      with 0.5 g of LiF and 8.75g of MA showed the most compatible properties for using
      bone cement, and thus it was assessed a candidate for a new bone cement along
      with CAC.

PMID- 12221709
TI  - Synthesis and characterization of hydroxyapatite crystals: a review study on the
      analytical methods.
AB  - For the synthesis of hydroxyapatite crystals from aqueous solutions three
      preparation methods were employed. From the experimental processes and the
      characterization of the crystals it was concluded that aging and precipitation
      kinetics are critical for the purity of the product and its crystallographic
      characteristics. The authentication details are presented along with the results
      from infrared spectroscopy, X-ray powder diffraction, Raman spectroscopy,
      transmission and scanning electron photographs, and chemical analysis. Analytical
      data for several calcium phosphates were collected from the literature,
      extensively reviewed, and the results were grouped and presented in tables to
      provide comparison with the data obtained here.

PMID- 12221710
TI  - Adhesion and growth of endothelial cell on amphiphilic PU/PS IPN surface: effect
      of amphiphilic balance and immobilized collagen.
AB  - Since natural blood vessels are lined with an endothelial cell (EC) monolayer, it
      is proposed that synthetic biomaterial surfaces be covered or seeded with
      endothelial cells for ideal nonthrombogenicity under normal conditions. The
      effects of the surface energy of hydrophilic-hydrophobic IPN on EC adhesion and
      growth were investigated. The human umbilical vein endothelial cells (HUVECs)
      were cultured on polyurethane (PU)/polystyrene (PS) IPN prepared by changing only
      the amphiphilic balance and controlling the microphase separated surface
      structure. The collagens were immobilized on the IPN surfaces for enhanced
      adhesion of HUVECs, and the morphology of the collagens immobilized highly
      depended on the surface energy of the IPNs. The stranded rope structure of the
      collagen molecules in the solution state was maintained only on the surface of
      the IPN with intermediate hydrophilicity. The adhesion and the proliferation of
      ECs on the nontreated IPN surfaces increased by increasing the hydrophobicity of
      the IPNs, and they were optimized on the collagen-treated IPN surface having an
      intermediate hydrophilicity. Finally, platelet adhesion was significantly reduced
      on the EC-hybridized surface of the IPNs.

PMID- 12221711
TI  - Synthesis and photopolymerization of trifunctional methacrylates and their
      application as dental monomers.
AB  - 1,1,1-Tris[4-(2'-hydroxy-3'-methacryloyloxypropoxy)phenyl]ethane (THMPE) and
      tris[4-(2'-hydroxy-3'-methacryloyloxypropoxy)phenyl]methane (THMPM) were
      synthesized and evaluated as base monomers in a dental composite system. The
      photopolymerization reactivity of the trifunctional methacrylates was similar to
      that of conventional 2,2-bis[4-(2'-hydroxy-3'-methacryloyloxy
      propoxy)phenyl]propane (bis-GMA). Of the three monomers (THMPE, THMPM, and bis
      GMA), THMPE has the greatest molecular volume, and its composite showed the
      lowest photopolymerization shrinkage of the composites derived from the three
      monomers. The water-solubility values for the light-activated composite resins
      formulated with THMPE and THMPM were much lower than that for a control bis-GMA
      composite. The trimethacrylates were not leached out into water from their
      corresponding photo-cured composites whereas the difunctional bis-GMA was eluted
      from its composite. The water sorption and flexural strength of the composite
      resins based on THMPE and THMPM were comparable to those of the bis-GMA
      composite. THMPE is promising for application as a photocurable dental monomer
      because of its good polymerization reactivity along with relatively low curing
      shrinkage and water-solubility of its photo-cured composite.

PMID- 12221713
TI  - Aquaporin-1 expression in the chick embryo chorioallantoic membrane.
AB  - The chick embryo chorioallantoic membrane (CAM) is commonly used in vivo to study
      both angiogenesis and anti-angiogenesis. Rapid membrane water transport is
      mediated by a family of molecular water channels, called aquaporins (AQPs), which
      have been identified in the epithelial and endothelial cells of higher
      vertebrates. AQP1, expressed in adsorptive and secretory epithelia, is also
      expressed in endothelial cells of capillaries and arteries. Its mRNA has been
      found in vascular smooth muscle cells (VSMCs) of arteries and capillaries, as
      well as in a subset of VSMCs of human atherosclerotic plaques. This study
      investigated the developmental expression of AQP1 in the chick CAM by Western
      blot and immunohistochemistry. Western blot results show that a major
      nonglycosylated band was observed with electrophoretic mobility of approximately
      28 kDa in the three developmental stages examined. Immunohistochemistry data
      demonstrate that AQP1 was clearly expressed in the ectodermal and endodermal
      epithelia, the vascular endothelium, and the VSMCs. Because little information is
      available on the behavior of microvessel AQP1 during angiogenesis in normal and
      pathological conditions, our data relative to the pattern of expression of AQP1
      in CAM blood vessels in normal conditions may be considered a useful tool to
      further investigate its modifications in several experimental conditions implying
      a stimulation or an inhibition of angiogenesis in the CAM assay.

PMID- 12221714
TI  - Craniosynostosis in Twist heterozygous mice: a model for Saethre-Chotzen
      syndrome.
AB  - Saethre-Chotzen syndrome is a common autosomal dominant form of craniosynostosis,
      the premature fusion of the sutures of the calvarial bones of the skull. Most
      Saethre-Chotzen syndrome cases are caused by haploinsufficiency for the TWIST
      gene. Mice heterozygous for a null mutation of the Twist gene replicate certain
      features of Saethre-Chotzen syndrome, but have not been reported to exhibit
      craniosynostosis. We demonstrate that Twist heterozygous mice exhibit fusions of
      the coronal suture and other cranial suture abnormalities, indicating that Twist
      heterozygous mice constitute a better animal model for Saethre-Chotzen syndrome
      than was previously appreciated.

PMID- 12221715
TI  - Morphological influence of ascorbic acid deficiency on endochondral ossification
      in osteogenic disorder Shionogi rat.
AB  - The influences of chronic deficiency of L-ascorbic acid (AsA) on the
      differentiation of osteo-chondrogenic cells and the process of endochondral
      ossification were examined in the mandibular condyle and the tibial epiphysis and
      metaphysis by using Osteogenic Disorder Shionogi (ODS) rats that bear an inborn
      deficiency of L-gulonolactone oxidase. Weanling male rats were kept on an AsA
      free diet for up to 4 weeks, until the symptoms of scurvy became evident. The
      tibiae and condylar processes of scorbutic rats displayed undersized and
      distorted profiles with thin cortical and scanty cancellous bones. In these
      scorbutic bones, the osteoblasts showed characteristic expanded round profiles of
      rough endoplasmic reticulum, and lay on the bone surface where the osteoid layer
      was missing. Trabeculae formation was deadlocked, although calcification of the
      cartilage matrix proceeded in both types of bone. Scorbutic condylar cartilage
      showed severe disorganization of cell zones, such as unusual thickening of the
      calcification zone, whereas the tibial cartilage showed no particular alterations
      (except for a moderately decreased population of chondrocytes). In condylar
      cartilage, hypertrophic chondrocytes were encased in a thickened calcification
      zone, and groups of nonhypertrophic chondrocytes occasionally formed cell nests
      surrounded by a metachromatic matrix in the hypertrophic cell zone. These results
      indicate that during endochondral ossification, chronic AsA deficiency depresses
      osteoblast function and disturbs the differentiation pathway of chondrocytes. The
      influence of scurvy on mandibular condyle cartilage is different from that on
      articular and epiphyseal cartilage of the tibia, suggesting that AsA plays
      different roles in endochondral ossification in the mandibular condyle and long
      bones.

PMID- 12221716
TI  - Analysis of the distribution of binding sites for the plant lectin Bandeiraea
      simplicifolia I-isolectin B4 on primary sensory neurones in seven mammalian
      species.
AB  - The purpose of the present study was to investigate the binding patterns of the
      plant lectin Bandeiraea simplicifolia I-isolectin B(4) (BSI-B(4)) to sensory
      neurones in seven mammalian species. The dorsal root ganglia and spinal cords of
      three rats, mice, guinea pigs, rabbits, flying foxes, cats, and marmoset monkeys
      were screened for BSI-B(4) using lectin histochemistry. BSI-B(4) binding was
      associated with the soma of predominantly small-diameter primary sensory neurones
      in the dorsal root ganglia and their axon terminals within laminae I and II of
      the superficial dorsal horn in all seven species. The similarities of lectin
      binding patterns in each of these species suggest that the glycoconjugate to
      which BSI-B(4) binds has a ubiquitous distribution in mammals, and supports the
      proposal that this lectin may preferentially bind to a subpopulation of sensory
      neurones with a similar functional role in each of these species.

PMID- 12221718
TI  - Sampling technique to discriminate the different tissue layers of growing antler
      tips for gene discovery.
AB  - The utilization of a deer antler model to study gene expression in tissues
      undergoing rapid growth has been hampered by an inability to sample the different
      tissue types. We report here a standardized procedure to identify different
      tissue types in growing antler tips and demonstrate that it can help in the
      classification of expressed sequence tags (ESTs). The procedure was developed
      using observable morphological markers within the unstained tissue at collection,
      and was validated by histological assessments and virtual Northern blotting. Four
      red deer antlers were collected at 60 days of growth and the tips (top 5 cm) were
      then removed. The following observable markers were identified distoproximally:
      the dermis (4.86 mm), the subdermal bulge (2.90 mm), the discrete columns (6.50
      mm), the transition zone (a mixture of discrete and continuous columns) (3.22
      mm), and the continuous columns (8.00 mm). The histological examination showed
      that these markers corresponded to the dermis, reserve mesenchyme, precartilage,
      transitional tissue from precartilage to cartilage, and cartilage, respectively.
      The gene expression studies revealed that these morphologically identified layers
      were functionally distinct tissue types and had distinct gene expression
      profiles. We believe that precisely defining these tissue types in growing antler
      tips will greatly facilitate new discoveries in this exciting field.

PMID- 12221717
TI  - Evolution of the biomechanical material properties of the femur.
AB  - The biomechanical performance of long bones is dictated by four key factors:
      element size, element shape, loading conditions, and material properties. Our
      understanding of the latter of these has been mostly limited to eutherian mammals
      and birds, which show similarity. Whether their possession of comparable material
      properties reflects common ancestry or independent evolution is uncertain. In the
      present analysis, we tested the bending strength, modulus, and failure strains of
      the femur and its pterygiophore homolog in actinpterygian fish. Sixty-nine
      specimens representing basal character states in seven major vertebrate crown
      clades were tested. These data were then coupled with avian and mammalian data
      from the literature and analyzed in an evolutionary context using phylogenetic
      character analysis. Mean values of 188 MPa for yield strength, 22.4 GPa for
      Young's modulus, and 8,437 mu epsilon for yield strain were obtained for the long
      bones. Analysis of variance (ANOVA) revealed comparable values between clades
      that span a 30,000-fold range of body mass. We conclude that material properties
      of the first long bones 475 million years ago were conserved throughout
      evolution. Major locomotory challenges to femora during vertebrate evolution were
      almost solely accomplished by modifications of element size and shape.

PMID- 12221719
TI  - Spatial distribution of fiber types within skeletal muscle fascicles from
      Standardbred horses.
AB  - Skeletal muscle fascicles from superficial and deep portions of semitendinosus
      (ST) and gluteus medius (GM) muscles from Standardbred trotters were analyzed
      with regard to muscle fiber type proportion (types I, IIA, and IIB) and spatial
      distribution. Muscle fibers within a fascicle were divided into four layers (L(1
      4)) from the fascicle periphery toward the center. The observed proportions of
      fiber types among layers were found to be statistically significantly different
      from a random distribution of fiber types. Type IIB fibers predominated in the
      peripheral layer, type I fibers prevailed in the layer underneath, and
      proportions close to the mean of the whole fascicles were observed in the central
      layer. This pattern of spatial distribution of fiber types within the layers of
      the fascicles was observed at all four muscle sampling sites. The functional
      significance of the common pattern is unknown, but possible functional roles are
      discussed.

PMID- 12221720
TI  - Regulation of osteoclast differentiation and function by receptor activator of
      NFkB ligand and osteoprotegerin.
AB  - The differentiation and functions of osteoclasts (OCs) are regulated by
      osteoblast-derived factors. Receptor activator of NFkB ligand (RANKL) is one of
      the key regulatory molecules in OC formation. Osteoprotegerin (OPG) is a novel
      secreted member of the TNF receptor superfamily that negatively regulates
      osteoclastogenesis and binds to RANKL. We examined the biological actions of
      macrophage-colony-stimulating factor (M-CSF), RANKL, and OPG on the
      differentiation of OCs isolated from cocultures of mouse osteoblastic cells and
      bone marrow cells. Preosteoclasts (pOCs) and OCs were characterized by their
      ultrastructure and the expression of OC markers such as tartrate-resistant acid
      phosphatase (TRAP) and vacuolar-type H(+)-ATPase. pOCs formed without any
      additives expressed TRAP, but showed little resorptive activity on cocultured
      dentine slices. TRAP-positive pOCs treated with M-CSF began to fuse with each
      other, but lacked a ruffled border (RB) and showed almost no resorptive activity.
      pOCs treated with RANKL became TRAP-positive multinucleated cells, which
      expressed intense vacuolar-type H(+)-ATPase along the RB membranes and exhibited
      prominent resorptive activity. Such effects of RANKL on pOCs were completely
      inhibited by the addition of OPG. OPG inhibited RB formation in mature OCs and
      reduced their resorptive activity, and also induced apoptosis of some OCs. These
      results suggest that 1) RANKL induces differentiation of functional OCs from
      pOCs, 2) M-CSF induces macrophage-like multinucleated cells, but not OCs, 3) OPG
      inhibits RB formation and resorptive activity in mature OCs, 4) OPG also induces
      apoptosis of OCs, and 5) RANKL and OPG are, therefore, important regulators of
      not only the terminal differentiation of OCs but also their resorptive function.

PMID- 12221721
TI  - Brain expansion in the chick embryo initiated by experimentally produced
      occlusion of the spinal neurocoel.
AB  - The brain expands in the early chick embryo from pressure generated by
      accumulation of cerebrospinal fluid (CSF) in a closed neural tube. The sealing of
      the neural tube occurs as the result of occlusion of the spinal neurocoel rostral
      to and before closure of the posterior neuropore. We have previously demonstrated
      the dependence of normal brain expansion upon intraluminal pressure. We had yet
      to demonstrate, however, that brain expansion actually depends upon natural
      occlusion of the spinal neurocoel. To demonstrate such dependence, we
      experimentally occluded the spinal neurocoels of embryos 5 hr younger than stage
      11 embryos (in which occlusion of the neurocoel occurs naturally). The stage 10
      chick embryos were cultured ex ovo and critically staged, and their spinal
      neurocoels were occluded using microcautery. All embryos were photographed
      immediately and at 5, 12, and 24 hr after cautery. Serial sections were made of
      selected embryos, in which the areas of both the brain and the head were
      measured. Wilcoxon-Mann-Whitney rank-sum nonparametric tests, Hodges-Lehmann
      estimators, bootstrapping techniques, and resampling randomization tests were
      used to determine whether the increases in the brain and head areas for the
      experimental embryos were significantly different from those of the control
      embryos during three distinct intervals of expansion: 0-5, 5-12, and 0-12 hr.
      From 0 to 5 hr, the brains of the precociously occluded embryos expanded
      significantly more than the brains of the non-occluded controls. From 5 to 12 hr,
      the brains of the embryos with naturally occluded neurocoels grew significantly
      larger than the brains of the embryos with precociously occluded neurocoels. At
      12 hr, there appeared to be no difference in brain size for these two groups. We
      conclude that the data support the hypothesis that brain expansion is directly
      dependent upon occlusion of the spinal neurocoel.

PMID- 12221722
TI  - Appearance and phenotype of murine follicular dendritic cells expressing VCAM-1.
AB  - The architecture of lymphoid follicles is determined by a series of interactions
      between lymphoid and follicular stromal cells. A cardinal population in the non
      lymphoid compartment is the follicular dendritic cell (FDC), whose communication
      with resting and activated B cells involves various adhesive interactions. The
      FDC phenotype variably includes the display of vascular cell adhesion molecule
      (VCAM-1). In this report we investigated the appearance and follicular tissue
      distribution of VCAM-1 in murine peripheral lymphoid tissues, and compared VCAM-1
      with other FDC markers using immunohistochemistry. Correlating the appearance of
      VCAM-1 with other murine FDC-associated markers (CR1.2 [complement receptor 1.2
      or CD35/21] and FDC-M1) revealed that the display of VCAM-1 is restricted to a
      subset of CR1.2-positive FDCs. We found that the expression of VCAM-1 antigen in
      the spleen or peripheral lymph nodes on FDCs requires antigenic stimulus, and
      that it coincides with germinal center formation. The VCAM-1 expression is
      associated with the appearance of mucosal addressin cell adhesion molecule
      (MAdCAM-1), with some slight differences in occurrence. The appearance of VCAM-1
      and MAdCAM-1 antigens on FDCs may serve as indicators of FDC activation.

PMID- 12221730
TI  - Orofacial pain: an educational focus.

PMID- 12221731
TI  - The Third Educational Conference to Develop the Curriculum in Temporomandibular
      Disorders and Orofacial Pain: introduction.
AB  - The principal aim of the Third Educational Conference to Develop the Curriculum
      in Temporomandibular Disorders and Orofacial Pain was to enhance the teaching of
      temporomandibular disorders (TMD) and orofacial pain to predoctoral dental
      students and to postdoctoral students in this field. Within this context, the
      conference sought to: (1) provide information regarding the current status of the
      predoctoral and postdoctoral teaching of TMD and orofacial pain, (2) present ways
      in which teaching of the basic sciences can be better integrated into the
      teaching of TMD and orofacial pain in the predoctoral and postdoctoral
      curriculum, (3) present ways in which the teaching of oral medicine can be better
      integrated into the teaching of TMD and orofacial pain in the predoctoral and
      postdoctoral curriculum, and (4) discuss how TMD and orofacial pain should be
      taught in a manner that is consistent with newly proposed accreditation
      standards. The papers addressing these specific aspects, as well as a summary
      paper on the conclusions from the conference, are presented in this issue of the
      journal.

PMID- 12221732
TI  - The study of temporomandibular disorders and orofacial pain from the perspective
      of the predoctoral dental curriculum.
AB  - This paper addresses questions 2 to 6 posed in the charge to the conference to
      discuss the study of temporomandibular disorders (TMD) and orofacial pain from
      the perspective of the predoctoral dental curriculum. This paper lends itself to
      an additional query: how much diagnostic and therapeutic skill relative to TMD
      and orofacial pain should a new graduate possess and demonstrate to be deemed
      competent in accordance with the definition of competence of the American Dental
      Association's Commission on Dental Accreditation? Although much of the content of
      this and the accompanying articles from the conference pertain to the TMD and
      orofacial pain curricula of dental schools in North America, most of what is
      presented here is universal to the teaching of the subject matter; therefore, it
      could be applied to educational institutions in other parts of the world. Indeed,
      an international survey relative to the teaching of TMD and orofacial pain would
      be of interest and value to dental schools worldwide.

PMID- 12221733
TI  - Integration of basic sciences into the predoctoral curriculum to study
      temporomandibular disorders and orofacial pain.
AB  - This paper outlines several aspects of the integration of basic sciences into the
      predoctoral dental curriculum. It addresses a number of the points or questions
      posed by the organizers of the Third Educational Conference to Develop the
      Curriculum in Temporomandibular Disorders and Orofacial Pain. The importance of
      the basic sciences for a comprehensive overview of knowledge bearing on
      temporomandibular disorders and orofacial pain is first emphasized, followed by
      considerations of what material should be taught and by whom. The paper concludes
      by considering at what stage of the curriculum this material should be included,
      how the pertinent basics sciences should be taught, and under what circumstances.
      Under the term "basic sciences" are included not only relevant biomedical or
      biologic sciences such as physiology and anatomy, but also the behavioral
      sciences such as psychology and cognitive science.

PMID- 12221734
TI  - Role of oral medicine in the teaching of temporomandibular disorders and
      orofacial pain.
AB  - This paper discusses the role of oral medicine in the teaching of
      temporomandibular disorders (TMD) and orofacial pain. Education in orofacial pain
      and TMD has traditionally been managed in academic dental settings as 2 distinct
      processes separate from the teaching of diagnosis and management as applied to
      systemic diseases and oral conditions. The rationale for such a segmented
      approach appears to have been driven by the concept that orofacial pain usually
      reflects a localized disease rather than arising as a component of more
      generalized systemic disease or modulated in intensity or morbidity by systemic
      pathology, generalized neurobiological, or behavioral contributors. Conversely,
      oral disease and head and neck manifestations of systemic disease often provoke
      pain as a major symptom. Management of such conditions should include acute and
      long-term pain management strategies when the underlying condition has no
      definitive cure and the pain is disabling. An argument is made for integrating
      the teaching of oral medicine and orofacial pain to enhance a broad-based
      approach to the assessment and management of primary pain disorders and to assure
      appropriate management of pain that is associated with mucosal disease and other
      forms of regional or systemic pathology including behavioral disorders that
      present as somatic and painful complaints.

PMID- 12221735
TI  - Development of orofacial pain programs in dental schools.
AB  - This paper discusses the critical issues that surround the development of an
      orofacial pain program in a dental school and suggests strategies to address
      them. Since the University of Minnesota has an established orofacial pain program
      involved in both predoctoral and postdoctoral teaching, clinical and basic
      research, and interdisciplinary patient care over the past 20 years, this article
      uses this as a model for development of an orofacial pain program. The proposal
      includes overall goals, background and rationale, specific aims, and program
      activities, including teaching, research, patient care, and financial and
      resource needs. These features may be of assistance to those considering the
      development of such programs in the United States and elsewhere in the world.

PMID- 12221736
TI  - Care of patients with temporomandibular disorders: an educational challenge.
AB  - The ability to recognize, evaluate, and manage patients with temporomandibular
      disorders is an important component of general dental practice. Therefore,
      information about these disorders should be a basic part of the dental
      curriculum. Although most dental schools do include this subject in their
      educational programs, its teaching typically involves the presentation of
      didactic material in formal lectures or in seminars. This teaching, however
      valuable, rarely includes the "hands-on" clinical experience of actually caring
      for this patient population. To address this lack of clinical experience, the
      Department of Oral Diagnostic Sciences of the School of Dental Medicine at the
      University at Buffalo has also developed a special elective program to offer
      dental students in their final undergraduate year the opportunity to obtain such
      experience.

PMID- 12221737
TI  - Reliability, validity, and clinical utility of the research diagnostic criteria
      for Temporomandibular Disorders Axis II Scales: depression, non-specific physical
      symptoms, and graded chronic pain.
AB  - AIMS: To analyze the reliability, validity, and clinical utility of the
      depression, non-specific physical symptoms, and graded chronic pain scales
      comprising the Research Diagnostic Criteria for Temporomandibular Disorders
      (RDC/TMD) Axis II. METHODS: Data resulting from independent longitudinal and
      cross-sectional epidemiological studies as well as randomized clinical trials
      conducted at the University of Washington and the University at Buffalo were
      submitted to descriptive, correlational, and inferential statistical analyses to
      evaluate selected psychometric properties of the RDC/TMD Axis II scales. RESULTS:
      Analyses of available data from both TMD clinical centers revealed good to
      excellent reliability, validity, and clinical utility for the Axis II measures of
      depression, somatization, and graded chronic pain. Specifically, data were
      presented comparing the RDC/TMD depression scale to the Beck Depression Inventory
      and the Center for Epidemiologic Studies Depression Scale; these data supported
      concurrent validity of the RDC/TMD measure and its use as a depression screening
      tool. Its clinical utility lies in its demonstrated usefulness for alerting TMD
      clinicians to potentially noteworthy depressive symptomatology in TMD patients.
      Others have shown that elevated somatization, the tendency to report non-specific
      physical symptoms as noxious or troublesome, is a predictor of poor TMD treatment
      outcome. The present analyses demonstrated that the RDC/TMD Axis II non-specific
      physical symptoms scale has acceptable reliability and that severe levels of
      somatization can potentially confound interpretation of the Axis I clinical
      examination. The graded chronic pain scale was demonstrated to have clinical
      utility for tailoring TMD treatment to levels of a patient's psychosocial
      adaptation. CONCLUSION: The major RDC/TMD Axis II measures demonstrate
      psychometric properties suitable for comprehensive assessment and management of
      TMD patients.

PMID- 12221738
TI  - Comparison of sleep quality and clinical and psychologic characteristics in
      patients with temporomandibular disorders.
AB  - AIMS: To explore the relationships between sleep quality, perceived pain, and
      psychologic distress among patients with temporomandibular disorders (TMD).
      METHODS: A total of 137 consecutive patients who sought care at the University of
      Kentucky Orofacial Pain Center for the management of TMD participated in this
      study and completed a battery of standardized, self-report questionnaires at
      their first clinic visit. The Pittsburgh Sleep Quality Index (PSQI) and the
      Multidimensional Pain Inventory (MPI) were used to measure patients' sleep
      quality and multiple dimensions of pain and suffering, respectively. The Revised
      Symptom Checklist-90 (SCL-90R) was used to evaluate psychologic symptoms. A
      median cutoff (PSQI total score: 10) divided the patients into 2 groups, i.e., 67
      poor sleepers and 70 good sleepers. RESULTS: There were no statistically
      significant differences in gender and age distributions between the 2 groups.
      Poor sleepers reported significantly higher scores than good sleepers on each of
      the 14 scales of the SCL-90R (P < .003) and on 7 of the 13 scales of the MPI (P <
      .05). Stepwise multiple regression analyses demonstrated that poorer sleep
      quality was predicted by higher pain severity (P < .001), greater psychologic
      distress (P < .05), and less perceived life control (P < .05). CONCLUSION: This
      study supports the frequent comorbidity of reported sleep disturbance, perceived
      pain severity, and psychologic distress in patients with TMD.

PMID- 12221740
TI  - Regulation of online pharmacies: a case for cooperative federalism.

PMID- 12221739
TI  - Temporomandibular joint nociception: effects of capsaicin on substance P-like
      immunoreactivity in the rabbit brain stem.
AB  - AIMS: To specify the regions of the brain stem that are characterized by changes
      in substance P (SP)-like immunoreactivity following activation of capsaicin
      sensitive afferents innervating temporomandibular joint (TMJ) tissues in New
      Zealand rabbits. METHODS: Capsaicin, an activator of small-diameter unmyelinated
      and thinly myelinated nociceptive afferent fibers, was administered unilaterally
      to the right TMJ of experimental animals. Another group received vehicle solution
      and served as controls. The animals were sacrificed 6 hours post-treatment
      through transcardial perfusion. Their brain stems were removed and sectioned, and
      SP-like immunoreactivity was assessed in serial horizontal sections. RESULTS: A
      decrease in brain stem SP-like immunoreactivity occurred ipsilateral to capsaicin
      application. This reduction was primarily localized in brain stem regions that
      correspond to the trigeminal main sensory nucleus, as well as subnucleus oralis,
      interpolaris, and caudalis of the trigeminal spinal tract nucleus. CONCLUSION:
      The present study revealed central nervous system changes following TMJ capsaicin
      treatment in rabbits.

PMID- 12221741
TI  - Interview with Michael H. Covert, FACHE, president, Washington Hospital Center,
      Washington, DC. Interview by Kyle L. Grazier.

PMID- 12221742
TI  - JCAHO: responding to quality and safety imperatives.

PMID- 12221743
TI  - Radical change: one solution to the nursing shortage.

PMID- 12221744
TI  - The role of the Internet in improving healthcare quality.
AB  - The Internet is a tool that has the potential to greatly affect and improve the
      quality of healthcare. This article discusses the ways in which the Internet is
      being utilized by healthcare administrators, physicians, and healthcare consumers
      to enhance the quality of care. Despite the Internet's growing popularity and
      use, several barriers remain that prevent its full implementation in the
      healthcare field. This article offers guidelines for administrators in using the
      Internet within their organizations.

PMID- 12221745
TI  - Recruitment, retention, and management of generation X: a focus on nursing
      professionals.
AB  - Two-thirds of the nurse workforce are now over the age of 40, and between 40
      percent and 60 percent of these nurses are expected to retire within the next 15
      years. Enrollment in programs at all nursing education levels is declining.
      Generation Xers, those born between 1963 and 1977, comprise between 10 percent
      and 15 percent of the current nursing workforce. Although relatively new to the
      workforce, Generation Xers have their own ideas of what constitutes an acceptable
      workplace, and usually the terms of their employment are not negotiable. Further
      complexity arises from the fact that management of this workforce falls primarily
      on Baby Boomers--those born between 1943 and 1960. Because of the events that
      molded their collective characteristics, Baby Boomers entered the workforce
      driven and dedicated. This group equates work with self-worth, contribution, and
      personal fulfillment. Many selected their profession not based on economic
      prospects but with the desire to make the world a better place. In addition,
      their competitive nature drives them to aspire for higher monetary compensation
      and titles. The challenge for healthcare leadership is understanding and creating
      harmony between these two generations. This article presents a summary of recent
      literature and studies that explain the basic distinctions in cultural
      characteristics and work ethics between Generation Xers and Baby Boomers. The
      summary, I hope, provides a guideline for recruiting, retaining, and managing
      Generation X workers in the nursing field.

PMID- 12221746
TI  - Measuring primary care practice performance within an integrated delivery system:
      a case study.
AB  - This article examines the use of an integrated performance measurement system to
      plan and control primary care service delivery within an integrated delivery
      system. We review a growing body of literature that focuses on the development
      and implementation of management reporting systems among healthcare providers.
      Our study extends the existing literature by examining the use of performance
      information generated by an integrated performance measurement system within a
      healthcare organization. We conduct our examination through a case study of the
      WMG Primary Care Medicine Group, the primary care medical group practice of
      WellSpan Health System. WellSpan Health System is an integrated delivery system
      that serves south central Pennsylvania and northern Maryland. Our study examines
      the linkage between WellSpan Health's strategic objectives and its primary care
      medicine group's integrated performance measurement system. The conceptual design
      of this integrated performance measurement system combines financial metrics with
      practice management and clinical operating metrics to provide a more complete
      picture of medical group performance. Our findings demonstrate that WellSpan
      Health was able to achieve superior financial results despite a weak linkage
      between its integrated performance measurement system and its strategic
      objectives. WellSpan Health achieved this objective for its primary care medicine
      group by linking clinical performance information to physician compensation and
      reporting practice management performance through the use of statistical process
      charts. They found that the combined mechanisms of integrated performance
      measurement and statistical process control charts improved organizational
      learning and communications between organizational stakeholders.

PMID- 12221748
TI  - Young managers. Walking tall.

PMID- 12221749
TI  - Buildings. A clean break.

PMID- 12221747
TI  - Perceived barriers to medical-error reporting: an exploratory investigation.
AB  - Medical-error reporting is an essential component for patient safety enhancement.
      Unfortunately, medical errors are largely underreported across healthcare
      institutions. This problem can be attributed to different factors and barriers
      present at organizational and individual levels that ultimately prevent
      individuals from generating the report. This study explored the factors that
      affect medical-error reporting among physicians and nurses at a large academic
      medical center located in the midwest United States. A nominal group session was
      conducted to identify the most relevant factors that act as barriers for error
      reporting. These factors were then used to design a questionnaire that explored
      the likelihood of the factors to act as barriers and their likelihood to be
      modified. Using these two parameters, the results were analyzed and combined into
      a Factor Relevance Matrix. The matrix identifies the factors for which immediate
      actions should be undertaken to improve medical-error reporting (immediate action
      factors). It also identifies factors that require long-term strategies (long-term
      strategy factors) as well as factors that the organization should be aware of but
      that are of lower priority (awareness factors). The strategies outlined in this
      study may assist healthcare organizations in improving medical-error reporting,
      as part of the efforts toward patient-safety enhancement. Although factors
      affecting medical-error reporting may vary between different organizations, the
      process used in identifying the factors and the Factor Relevance Matrix developed
      in this study are easily adaptable to any organizational setting.

PMID- 12221750
TI  - Buildings. Dining on empty.

PMID- 12221751
TI  - Buildings. Watch this space.

PMID- 12221752
TI  - Data briefing. Money for health.

PMID- 12221753
TI  - Stress in dental specialists: a comparison of six clinical dental specialties.
AB  - OBJECTIVE: To describe and compare the levels of stress reported by dental
      practitioners working within clinical dental specialties. METHOD: Questionnaire
      survey of 220 dental practitioners identified from the General Dental Council
      lists of specialist practitioners in the following clinical specialties:
      orthodontics, paediatric dentistry, restorative dentistry, endodontics,
      periodontology, prosthetic dentistry. FINDINGS: The clinical specialties did not
      differ in their reported levels of stress. Practitioners working in the field of
      paediatric dentistry reported the highest median levels of reported stress for
      three of the four scales, though this trend was not significant. CONCLUSIONS: The
      practitioners surveyed from six clinical specialties did not experience
      significantly different sources of stress.

PMID- 12221754
TI  - Oral ill-health and deprivation among patients of a general dental practice in
      South Wales.
AB  - PURPOSE OF STUDY: This study aims to establish and report on whether individuals
      from deprived areas suffer more ill health than adults from areas considered not
      to be deprived when visiting a general dental practice. BASIC PROCEDURES: Between
      December 1998 and June 1999 registered dental patients over 18 years of age
      attending for routine care completed a questionnaire measuring functional,
      experiential and psychosocial impact of oral ill health. In addition the clinical
      impact of ill health was established from the patient examination and record
      card. Clinical outcome was assessed by numbers of standing teeth, oral health was
      assessed using the Subjective Oral Health Status Indicators (SOHSI). The
      patient's postcode was used to categorise individuals from areas of different
      deprivation states. MAIN FINDINGS: 99% were dentate with 88.4% having more than
      20 teeth. A total of 71.8% were able to eat satisfactorily, 88.2% were able to
      speak satisfactorily, 54.6% were discontent, 99.4% were worried about their oral
      health and appearance, 62.8% were satisfied with their oral health, 44.8%
      experienced discomfort, 65.8% experienced other symptoms, and 86.8% experienced
      'general well-being'. No differences were observed for clinical measures between
      the deprived groups. Only three out of eight oral health measures showed any
      differences between the deprived groups, namely, ability to speak, discontent and
      general well-being. More individuals from deprived areas experienced these
      impacts. PRINCIPAL CONCLUSIONS: It was anticipated that individuals from deprived
      areas would experience greater ill-health: this outcome was not as marked as
      expected.

PMID- 12221755
TI  - Is computer-assisted learning effective for GDPs?

PMID- 12221756
TI  - Advances in prosthetic dentistry.
AB  - Until recently removable prostheses were the only form of treatment for those who
      had lost all or most of their natural teeth, while for the partially dentate,
      dentures were perceived as a poor substitute for a fixed restoration, lacking
      stability and prone to increasing oral disease. Subsequent studies demonstrated
      the functional benefits of removable partial dentures (RPDs) and how they could
      be used with minimal oral harm.

PMID- 12221757
TI  - Resin-retained bridges re-visited. Part 1. History and indications.
AB  - Resin-retained bridges have been used clinically since the 1970s, and offer a
      more conservative approach to the restoration of edentulous spaces than
      conventional bridgework. They are easy to place, cheap to fabricate and have been
      shown to be cost effective. Despite this, they are not frequently used in general
      dental practice and they have an undeserved reputation for failure. Since their
      initial introduction, they have undergone a number of changes to their method of
      retention, and the materials used in their construction. This has resulted in a
      predictable, aesthetic restoration which, barring the use of implants, is often
      the treatment of choice where teeth adjacent to an edentulous space are minimally
      or not restored. This first article details the history, advantages, indications,
      and designs of resin-retained bridges.

PMID- 12221758
TI  - Variant Creutzfeldt-Jakob disease--a problem for general dental practitioners?
AB  - Over a hundred deaths from variant Creutzfeldt-Jakob disease (vCJD) have now been
      recorded. The incubation period for vCJD may be up to 40 years and the number of
      asymptomatic carriers in the population could be as many as 100,000. Confirmed
      iatrogenic transmission of other human transmissible spongiform encephalopathies
      raises the possibility of cross-infection from apparently healthy persons who are
      incubating vCJD. Decontamination techniques routinely used in general dental
      practice are incapable of inactivating the infective protein responsible for
      transmitting the disease. So far, no evidence exists to preclude the risk of
      iatrogenic infection occurring during dental procedures. The author reviews
      present knowledge of the infective agent, its transmissibility, its origins,
      current guidelines and the implications for dental practice.

PMID- 12221759
TI  - Can we avoid errors in family practice?

PMID- 12221760
TI  - An easy way to analyze E/M coding for group practices.

PMID- 12221761
TI  - Prescription writing to maximize patient safety.

PMID- 12221762
TI  - Reducing risks for patients receiving warfarin.

PMID- 12221764
TI  - The power of two: improving patient safety through better physician-patient
      communication.

PMID- 12221763
TI  - Four principles for better test-result tracking.

PMID- 12221765
TI  - When medical errors hit home.

PMID- 12221770
TI  - Responding to consumer demand for choice, flexibility.

PMID- 12221771
TI  - Medicare+Choice enrollees bring concerns to Capitol Hill.

PMID- 12221772
TI  - Essential, affordable health care for all.

PMID- 12221773
TI  - Helping children cope in a violent world.

PMID- 12221774
TI  - IOM highlights health disparities: implications for health plans.

PMID- 12221775
TI  - Celebrating health, providing care.

PMID- 12221776
TI  - Gaining credibility with providers. Interview by Carl Peterson.

PMID- 12221777
TI  - Medical animation offers bold new way to communicate.

PMID- 12221778
TI  - National campaign yields positive results for patients with diabetes.

PMID- 12221779
TI  - Maintaining a mission. Medicaid plans focus on pharmaceutical care.

PMID- 12221780
TI  - Health care workforce shortages. What can the industry do to stem the crisis?

PMID- 12221781
TI  - Field of dreams. If you build it, will consumers come?

PMID- 12221782
TI  - Congress approves bioterrorism bill.

PMID- 12221783
TI  - Ready for HIPAA? Take steps to protect patient privacy before it's too late.
AB  - The Health Insurance Portability and Accountability Act (HIPAA) will become
      effective April 2003 and will require you to address patient privacy issues
      throughout your ED. Use sign-in sheets that conceal the patient's name. Give
      patients beepers instead of calling out names in the waiting room. Use a special
      code to give patients additional privacy.

PMID- 12221784
TI  - Cut medication errors in half with ED pharmacist.
AB  - Using a dedicated pharmacist in the ED can drastically cut costs and medication
      errors. The pharmacist is a valuable resource for physicians, who can obtain
      current information about complex drug interactions. Nurses receive regular
      inservices about medication administration. Monthly costs were cut by $61,000 due
      to more appropriate utilization of medications.

PMID- 12221785
TI  - ED managers react to smallpox vaccine update.
AB  - In updated recommendations, a Centers for Disease Control and Prevention advisory
      committee says that a small group of predesignated personnel should receive
      smallpox vaccinations, but not the general public or other health care workers.
      Some managers insist that any group who could be exposed without advance notice
      should be vaccinated. There is a concern about time off for vaccination if an
      exposure occurs. The risk of side effects is a concern.

PMID- 12221786
TI  - Learn how bioterrorism bill will affect your ED.

PMID- 12221787
TI  - Grow with it. The role of plants in health care facilities.

PMID- 12221788
TI  - An administrator's prayer.

PMID- 12221789
TI  - Medicine and the Internet. Opportunities in cyberspace.

PMID- 12221790
TI  - Follow the torch. Identifying and developing physician leaders.

PMID- 12221792
TI  - New ways to manage late-night calls .

PMID- 12221791
TI  - Measure twice, cut once. Examine internal processes before renovating.

PMID- 12221793
TI  - Six things you can do now to change your organization's future ... and keep your
      job and your sanity.
AB  - Health care administrators may not have the authority of CEOs in other
      industries, but they can guide the change process in their organizations. By
      making choices, building alliances, nurturing other leaders, overcoming
      obstacles, communicating results and respecting themselves, practice managers can
      provide instrumental leadership to their groups.

PMID- 12221794
TI  - Service vs. satisfaction. The key to a competitive edge.
AB  - Understanding the difference between patient service and satisfaction can provide
      any medical practice with the competitive advantage to retain existing patients
      and attract new ones.

PMID- 12221795
TI  - See something you like? Patient surveys via the Internet.
AB  - Can e-mail surveys to patients serve as a reliable, cost-effective method for
      gathering information? Six practices with MHMA members participated in a project
      to learn if Internet surveys can collect reliable data quickly and economically.

PMID- 12221796
TI  - Negotiate or lose. Tactics for getting acceptable managed care fee reimbursement.
AB  - Getting the money your practice earns from providing managed care requires you to
      take the initiative. Know the details of each contract, know your practice's
      strengths, have a fair fee schedule, apply your leverage and be willing to walk
      away if a poor deal is all that's forthcoming.

PMID- 12221797
TI  - Balancing act. A case study of weighing incentives in a physician compensation
      plan based on collections.
AB  - How one group practice re-evaluated traditional methods for compensating
      physicians in the face of changing reimbursement for their services, new
      organizational structures within which doctors practice, pressure to improve
      patient satisfaction, and increasingly complex regulations.

PMID- 12221798
TI  - Achieving quality in assisted living.

PMID- 12221799
TI  - Resident contracts: getting it right.

PMID- 12221800
TI  - Assisted living: a risky business.

PMID- 12221801
TI  - Restored function, renewed hope.

PMID- 12221802
TI  - Identifying Medicare status codes.

PMID- 12221803
TI  - [The health of the child during eruption of the deciduous teeth].
AB  - Teething is a physiological process that may be marked by local regional or
      general physiopathologies. We have studied these disorders in a sample of 499
      children whom we followed from the age of 5 until the age of 30 months. The study
      consisted in a clinical endobuccal examination. Each month we recorded the order
      and the eruption date of the tooth or teeth and the disturbances that arise
      during the process or after, if any. We expose the results of this study in this
      paper. We collected local and general disturbances during the primary teeth
      eruption period. We considered that in certain conditions these disturbances
      could be to the eruption process. Teething is certainly a natural process,
      however considering its traumatic impact on the young child, we should not reject
      the aetiology in the justification of the disturbances observed in this process
      and seek another one which might not be valid.

PMID- 12221804
TI  - [Management of dental records: an example of the Department of Restorative
      Dentistry of the School of Odonto-Stomatology in Abidjan].
AB  - The patient's file is often mismanaged because of the crowd and the frequency of
      emergencies caused by pain. The practitioner is worrying about handling it in
      first place. The objective of this work is to recall the importance of a good
      management of the dental records and to suggest a charting system. The interest
      of the dental chart, fundamental part of the patient dental file, is described
      before developing the implications related to an adequate management. The
      charting system of the service of Operative Dentistry and Endodontics of Abidjan
      Dental school is described. It translates the target of a good dental records
      management, which presents appreciable assets for practitioner, patient and
      administration.

PMID- 12221805
TI  - Caries prevalence and some caries related factors for 12 year-old children from
      Vientiane and Luang Prabang provinces in Lao People's Democratic Republic.
AB  - Caries prevalence and some caries related factors for 100 twelve-year-old
      children from Vientiane and Luang Prabang provinces in Lao People's Democratic
      Republic were studied. The caries prevalence was high showing a DMFT of 4.6 with
      9% of the children being caries free, the D comportment contributed mostly to the
      DMFT and the Significant Caries Index (Sic Index) was DMFT 8.0. As to the caries
      related factors, 25% of the children were in the high mutans class, 31% of the
      group had high or very high Lactobacilli scores and 84-88% studied took local
      sweet snacks, chips and sweet drinks every day. Taking into consideration the
      high caries prevalence, the mutans streptococci distribution, the frequent intake
      of sweets and also the relatively low fluoride concentration in the drinking
      waters, oral health preventive programmes are indicated to prevent a possible
      caries epidemic in Laos in the future.

PMID- 12221806
TI  - [Appearance in dental practice: opportunity or puerile embellishment?].
AB  - Appearance and style of the dental practitioner influences the perception of the
      patients. The objectives of this work are threefold: To raise the awareness of
      the patient regarding style and appearance; Evaluate whether style and appearance
      contribute to creating a relationship of trust between the patient and the
      practitioner; Make suggestions on enhancing one's appearance. A questionnaire was
      sent out to practitioners, senior patients of both sexes, and to children of four
      years or older. The evaluation shows that patients make their own judgement in
      the practitioner as of the first encounter, and cleanliness and elegance are
      highly rated. Make up is to be applied in a discreet fashion so as not to shock
      or scare the patients. 95% of the persons surveyed were partial to the external
      appearance of the dentist. Appearance and style therefore matter, and may not be
      considered superfluous.

PMID- 12221807
TI  - [An in vitro study of the action of kola nitida on bacterial strains implicated
      in dental caries and periodontal diseases].
AB  - The Nitida Kola is a substance extracted from the kolanut. In West Africa its use
      by chewing is widespread among the Manding people. It's said to have tonic,
      stimulant and aphrodisiac characteristics and even recent studies have shown that
      it has antibacterial characteristics. The aim of this study is to make an
      estimation of the Nitida Kola's effects on different bacterial species involved
      in the two main oral and dental pathologies (teeth decays and periodontal
      illnesses). The obtained results indicate that the kola extract is not effectual
      against the tried-out bacteria at regular dose used by chewing.

PMID- 12221808
TI  - [Periodontal diseases in a university setting in Ivory Coast].
AB  - The aim of this study was to measure the prevalence and severity of periodontal
      diseases, and also to evaluate periodontal treatment needs of the students of
      Abidjan University, in Ivory Coast. 647 students were randomly selected and
      interviewed to determine age, sex and oral hygiene habits; the subjects were
      examined for tooth mobility, plaque, calculus, gingival bleeding, periodontal
      probing depths and gingival recessions. The oral hygiene was insufficient: 86.08%
      of the subjects presented calculus--The average of sextants presenting gingival
      bleeding was to 4.03 and to 3.43 for calculus. The prevalence and severity of
      periodontal pockets were low: only 0.36 sextants on average presented pockets of
      4-5 mm and 0.025 sextants presented pockets of 6 mm or more. As concerns
      periodontal treatment needs, 89.64% of subjects needed oral hygiene advises,
      84.85% needed scaling/root planning, and 1.39% needed complex periodontal
      treatment. Our findings confirm the fact that destructive periodontal disease is
      not an inevitable consequence of gingivitis. The information, screen, and
      prevention should begin reality in our daily practice.

PMID- 12221809
TI  - Smoking behaviour and knowledge in high school students in Riyadh and Belfast.
AB  - Smoking is one of the risk factor associated with onset, severity and progression
      of periodontal disease. AIM: The aim of the study was to examine the smoking
      behaviour and dental health knowledge of high school students in Riyadh and
      Belfast. MATERIALS AND METHODS: Eight schools from Riyadh and 6 from Belfast were
      randomly selected by cluster distribution sampling method. Two hundred and ninety
      students from Riyadh and 144 from Belfast were included giving an overall
      response rate of 85%. The age range was between 16-17 years. A questionnaire was
      used to assess demography, smoking habits, dental health knowledge and oral
      hygiene practices. RESULTS: The results showed that 18% of students were smokers;
      24% in Belfast and 15% in Riyadh (x2 (1) = 4.29: P = 0.04). 24% of students in
      Belfast and 56% in Riyadh smoked at least 1 cigarette per day. 61% of students
      had bleeding gums although 85% stated that they brushed their teeth at least
      daily. Bleeding on brushing was common with 53% of Belfast students compared with
      65% from Riyadh. Students in Belfast (2.51 +/- 1.15) had significantly higher
      mean scores for their knowledge about gum health compared with Riyadh students
      (2.21 +/- 1.44) (t = 2.29: P = 0.02). There was no differences in knowledge about
      oral health and smoking between the students. However, non-smokers from Belfast
      and Riyadh (3.32 +/- 1.60) had greater knowledge about oral health and smoking
      than those who smoked (2.81 +/- 1.45) (t = 2.73: P = 0.007). There was no
      difference in knowledge about gum health between smokers and non-smokers.
      CONCLUSIONS/RECOMMENDATIONS: Smoking is more prevalent in Belfast but more
      cigarettes are smoked in Riyadh. As non-smokers had greater knowledge of the ill
      effects of smoking upon their oral health, there is a need to develop location
      specific interventions to control smoking habits in late adolescence.

PMID- 12221810
TI  - [Patients, practitioners, faculty and dental esthetics: the same level of
      perception?].
AB  - The aim of this study was to evaluate the importance of the dental aesthetic for
      the patients, the dental surgeon and the dental teachers by the study of the
      consultation reason, the complaints, the post-university congress program, the
      practical program of the dental students and the programs of the IADR congress.
      It appears that in odontology, patients ask strongly for aesthetic care, in
      consultation and litigation. The content of congress and professional literature
      shows that dental surgeons answer to that request. Only the practical teaching
      was a bit less but it was recently modify. The research workers are also very
      interesting for aesthetic care.

PMID- 12221811
TI  - But will you be able to buy it at Radio Shack? Researchers design tooth that can
      receive digital signals.

PMID- 12221812
TI  - BIOLASE and UCLA successfully complete first Waterlase sinus surgery in the
      United States.

PMID- 12221813
TI  - Position paper: American Academy of Periodontology's guidelines for periodontal
      therapy.

PMID- 12221814
TI  - Thriving in a tough economy.

PMID- 12221815
TI  - Extraction of teeth. Some general observations.

PMID- 12221816
TI  - Immediately restored single-tooth implants. Shortening treatment time to increase
      patient acceptance.

PMID- 12221817
TI  - Porcelain veneers. Problems and solutions.
AB  - Porcelain veneer restorations require close attention to detail from beginning to
      end. It is often prudent to go slowly when working with these cases. Patients
      receiving them have high expectations that go beyond considerations of function
      alone. Many problems are encountered when porcelain veneers are used to improve
      the appearance of the teeth. Avoiding and overcoming these problems first
      requires identification of the causes of the problems, followed by changes in
      clinical techniques. Success is the result of careful selection of teeth to
      receive veneers; preparing teeth in a manner that optimizes the aesthetic
      potential of the veneer; employing techniques that maximize the strength of both
      the veneer and its adhesive bond to the tooth; utilizing high-quality provisional
      veneers; insisting on a precision fit; and paying attention to the details of
      adhesive bonding protocols.

PMID- 12221818
TI  - Initial management of temporomandibular disorders.
AB  - The existing dental literature does not support the superiority of any one type
      of treatment to manage TMD. Few studies meet rigorous scientific standards of the
      randomized clinical trial. This has led to enormous controversy. The initial
      management of TMD does not have to be controversial. Noninvasive, reversible
      modalities can be employed that carry very little risk and a high degree of
      success (Table 4). The success rate of this approach has been studied and
      determined to be 75% to 90%. Of course, not every patient will get better with
      this approach. For those who do not improve more advanced techniques must be
      used, and referral to specialists in TMD, neurology, and rehabilitation medicine
      may be required. A few patients will need surgery. Initial treatment of TMD
      requires relatively simple modalities, such as patient education, adherence to a
      soft diet, reducing oral habits, self-directed home physical therapy, muscle
      relaxation, the use of medication, and the proper use of bite plates. The
      majority of TMD patients will respond successfully to these basic treatments.

PMID- 12221819
TI  - From bridges to implants. The new paradigm for general practice.

PMID- 12221820
TI  - Mineral trioxide aggregate endodontic obturation with Nd:YAG laser disinfection.

PMID- 12221821
TI  - Oral healthcare for infants.

PMID- 12221822
TI  - Dentistry's orphan.

PMID- 12221823
TI  - Computers in the treatment room. What are you waiting for?

PMID- 12221824
TI  - Implants in restorative dentistry: new procedures, new opportunities.

PMID- 12221825
TI  - Composites in the mainstream.

PMID- 12221826
TI  - First person. The slow road back.

PMID- 12221827
TI  - Consultant development. Role rehearsal.
AB  - Most newly appointed consultants have had no training in management. Consultants
      who have been in post for several years may need extra management development to
      become clinical directors, medical directors or chief executives. A training
      scheme initiated in the West Midlands appears to have been well received and is
      being extended.

PMID- 12221828
TI  - Globalisation and public health--call for a 'health of the people bill' from the
      Nuffield Trust.

PMID- 12221829
TI  - [Quality control program in a group of Spanish public hospitals (1993-2001)].
AB  - INTRODUCTION: The INSALUD (National Healthcare Institute) is a public institution
      that manages the provision of health services for 15 million Spanish people.
      INSALUD developed a quality control program for specialist care, which involved
      its 80 hospitals. OBJECTIVES OF THE PROGRAM: To promote leadership among the
      managers of quality assurance programs, to involve in the improvement of quality
      all the employees of the organization and to set out the Institution's following
      strategic outlines: to direct the services towards the needs of the population,
      to improve the quality and effectiveness of the care procedures, to minimize
      risks and to improve the information system. EQUIPMENT AND TECHNIQUES: The
      Management Contract, i.e. the main tool of specialist care management, included a
      Quality Control Program common to all the hospitals involved. The Program was
      divided in the following three parts: common improvement goals, monitoring of
      indicators and guidelines of the organization. OUTCOME AND FINDINGS: All the
      hospitals involved introduced their own quality assurance program which
      incorporated the Institution's Quality Control Program. The majority of the
      objectives assessed showed a continuous improvement of the outcome. The
      experience of the 1993-2001 INSALUD Quality program can prove to be very useful
      for the new Healthcare Services of the Autonomous Communities resulting from the
      decentralization of the healthcare provision of services in Spain.

PMID- 12221830
TI  - Towards international strategic partnership management between the ICT and health
      care sectors: seven pillars of effectiveness.
AB  - This study identifies seven key characteristics of effective strategic
      partnership management issues between the Information and Communication (ICT) and
      health care sectors. It underscores the implications for international health
      community, based on experiences in Canada, Germany, Sweden and the United
      Kingdom.

PMID- 12221831
TI  - Disability, poverty and development.
AB  - Disability is both a cause and consequence of poverty. Eliminating world poverty
      is unlikely to be achieved unless the rights and needs of people with
      disabilities are taken into account. According to the United Nations, one person
      in 20 has a disability. More than three out of four of these live in a developing
      country. More often than not they are among the poorest of the poor. Recent World
      Bank estimates suggest they may account for as many as one in five of the world's
      poorest. Disability limits access to education and employment, and leads to
      economic and social exclusion. Poor people with disabilities are caught in a
      vicious cycle of poverty and disability, each being both a cause and a
      consequence of the other. A large proportion of disability is preventable.
      Achieving the international development targets for economic, social and human
      development will undoubtedly reduce the levels of disability in many poor
      countries. However, general improvements in living conditions will not be enough.
      Specific steps are still required, not only for prevention, but also to ensure
      that people with disabilities are able to participate fully in the development
      process, obtain a fair share of the benefits, and claim their rights as full and
      equal members of society. An integrated approach is required, linking prevention
      and rehabilitation with empowerment strategies and changes in attitudes. This
      paper assesses the significance of disability as a key development issue, and its
      importance in relation to poverty, human rights, and the achievement of
      internationally agreed development targets. It also sets out ways in which
      development co-operation, including DFID's own work, can help incorporate the
      rights and needs of people with disabilities into the mainstream of poverty
      reduction work and the achievement of human rights.

PMID- 12221832
TI  - New development of the University of Tokyo teaching hospital.
AB  - This paper is introducing the evolution and present situation of health facility
      design in Japan. Statistical international comparative study in terms of
      historical, cultural, geographical and socio-economical overview as well as
      demographic and epidemic health issues in addition to the brief review of the
      past, present and future of these issues are discussed. Moreover, design
      characteristics of contemporary Japanese general hospitals in the forms of eight
      nick names are presented, mainly introducing the University of Tokyo Teaching
      Hospital, as a case study, which is regarded as one of the most recent
      redevelopment of tertiary teaching hospital projects in Japan.

PMID- 12221833
TI  - European trends and challenges.
AB  - In 1996 HOPE produced a discussion paper on the future role of hospitals, not so
      much in order to defend hospitals against widespread negative images in the cost
      calculation reforms, sometimes replacing the former hospital centrism by an even
      exaggerated hospitalocynism. The HOPE paper stimulates hospitals to consider
      trends in society, in healthcare and medicine and in patient expectations and it
      concludes by inviting them to transform the "bed-centred hospital into a health
      centre as part of a wider healthcare network". In doing this, hospitals are
      confronted with major paradoxes in the turbulent "changes" and so-called changes
      healthcare and hospital policy are going through all over Europe. I just
      summarise some three of them: change vs being changed? cost vs investment?
      compete vs co-operate?

PMID- 12221834
TI  - Health care systems in Western Europe: an analytical approach.
AB  - Health care in the countries of Western Europe can be defined as a complex
      process of continuous innovation, i.e. of constantly implementing new
      combinations of science, technology, organisation, economics, politics,
      philosophy, opinions and fashion. Any element of this definition can influence
      the course of the health care process, whether or not combined with one or more
      of the other elements. This definition implies that health care systems as well
      as health care policy of the countries of Western Europe differ considerably. If
      we define a health care system as the legal and organisational framework,
      directed at producing, distributing, managing, regulating, supervising, co
      ordinating and controlling health care activities in order to realise defined
      social health care values, no country can narrowly be compared to any other
      country. Such a comparison produces a huge basket of facts from which one can
      draw one conclusion only: each country acts to its own liking. The same applies
      for the concept of health care policy, i.e. a chosen course to achieve pre-set
      strategic objectives. Here too, every country acts to its own liking, where
      nobody is right and nobody is wrong. Consequently, the universal health care
      system does not exist. Consequently also, the analyst who takes a closer look at
      the health care systems of the countries of Western Europe, trying to map the
      differences, will discover a rather messy picture. All this being said, how do we
      deal with two burning questions? The first is: how can it be that, relatively
      speaking, the people of Western Europe are so healthy? Secondly: how do we clean
      up the mess or, in other words, how do we reform health care?

PMID- 12221835
TI  - [Laser Doppler flowmetry in evaluating the effectiveness of magnetolaser exposure
      in patients with gonarthrosis].
AB  - The aim of the study was estimation of the effects of laser therapy on
      microcirculation in osteoarthritis with application of laser doppler flowmetry
      (LDF). A total of 20 patients were treated. 10 procedures of the laser therapy
      were performed (Mlada unit, 0.85 micron, 15 mV, 5 min). LDF proved informative in
      complex estimation of blood microcirculation and efficiency of laser therapy in
      patients with osteoarthritis.

PMID- 12221836
TI  - [Photophoresis of methyluracil ointment in the complex treatment of
      temporomandibular pain syndrome].
AB  - The authors recommend to expand laser radiation zones, i.e. to expose to infra
      red laser radiation not only the trigger points and the temporomandibular joint
      but also paravertebral area, in the treatment of patients with temporomandibular
      painful dysfunctional syndrome (TMPDS). Experimental and clinical data have shown
      that photophoresis of 10% methyluracilic onitment is more effective than laser
      therapy in mild and moderate TMPDS.

PMID- 12221837
TI  - [The question of mechanisms of the immunotropic effect of mineral drinking
      waters].
AB  - Drinking of mineral waters influences human immune system. Among the mechanisms
      of this action is a stress effect confirmed by increasing levels of
      glucocorticoids, catecholamines, by hyperglycemia, etc. Regular drinking of
      mineral water brings about adaptation. Development of long-term adaptation
      provokes defensive cross effects. It is suggested that an immunotropic action of
      mineral waters may be a manifestation of a defensive cross effect of the organism
      adaptation. Immunostimulation may also be related to suppression of T-suppressors
      activity and changes in cytokines levels.

PMID- 12221838
TI  - [Clinico-immunologic monitoring of patients with gastroesophageal reflux during
      recuperative treatment].

PMID- 12221839
TI  - [Galvanization of a region of the liver in combination with use of huminate in
      complex recuperative treatment of patients having undergone surgery on the
      stomach and biliary tract].
AB  - We studied efficiency of intratissue electrophoresis of 1% huminate solution in
      rehabilitation of patients operated on the stomach and biliary tracts with
      functional deficiency of the stress-limiting system (SLS). The above
      electrophoresis stimulates SLS and promotes earlier start of therapeutic
      response.

PMID- 12221840
TI  - [Dynamics of the morphofunctional status of digestive organs in patients with
      chronic gastroduodenitis during monotherapy with sulfate sodium-calcium mineral
      water].
AB  - The authors describe morphofunctional changes in gastroduodenal tract in patients
      with chronic gastroduodenitis. Some of them have previously undergone
      laparoscopic cholecystectomy for cholelithiasis. Balneotherapy with mineral water
      "Uvinskaya" has a good effect in the above disease and therefore is recommended
      for prevention and treatment of patients with chronic gastroduodenitis as well as
      for prevention of repeated cholelithiasis after cholecystectomy.

PMID- 12221841
TI  - [Cryoamplipulse therapy in treating patients with chronic constipation].
AB  - 120 patients with chronic constipation (CC) were examined using assessment of the
      immune status, rectoromanoscopy, esophagogastroduodenoscopy, myography, stool
      examination for volatile fatty acids and dysbacteriosis. The patients were
      divided into three groups. Group 1 (n = 58) received cryoamplipulsetherapy, group
      2 (n = 29)--creotherapy, group 3 (n = 33)--amplipulsetherapy. Changes in clinical
      and functional indices show that the response in group 1, 2 and 3 was 88, 75 and
      68%, respectively.

PMID- 12221842
TI  - [Use of zinc sulfate and sodium thiosulfate electrophoresis in treating patients
      with intestinal dysbacteriosis].
AB  - Electrophoresis of 2% zinc sulfate solution and 3% sodium thiosulfate solution
      was used in combined treatment of intestinal dysbiosis with high Candida
      proliferation in 79 patients. 77 controls received standard therapy. It is shown
      that such electrophoresis produced positive changes in the clinical picture of
      the disease, significantly suppressed growth of Candida fulgi, improved function
      of the liver as shown by a rise in the amount of total protein and hemoglobin,
      lower bilirubin concentrations in the blood.

PMID- 12221843
TI  - [Effect of general carbon dioxide baths on processes of remodeling and diastolic
      function of the heart in patients with ischemic heart disease after myocardial
      infarction].
AB  - The trial included 63 postmyocardial infarction (PMI) men aged 40-65 years with
      cardiac failure (CF) NYHA functional class I-II and/or left ventricular (LV)
      diastolic dysfunction. The patients were randomized into two groups: the study
      group and the controls. The former received medication plus carbon dioxide baths,
      the latter received medication only. As shown by two-dimensional echocardiography
      there were no significant differences between the groups by LV function, volume,
      myocardial mass. In patients of the study group, ejection fraction increased in
      75% patients, in controls--in 62%. In those who have taken baths ejection
      fraction increased if it was low before the treatment. Transmitral blood flow
      measured with spectral dopplerography indicated significant changes in diastolic
      function in the study group. Thus, balneotherapy with carbon dioxide baths
      significantly improves LV diastolic function and myocardial contractility in
      patients with impaired LV systolic function.

PMID- 12221844
TI  - [Use of laser irradiation for correcting involutionary dysregulation in men and
      women].
AB  - Basing on their experience with 480 patients, the authors propose original
      methods of laser correction of involutionary dysregulation in men and women aged
      40-60 years depending on severity of clinical and dysregulatory manifestations.
      They discovered mechanisms of correction of humoral-homeostatic imbalance,
      determined patients who need sanitation, designed measures preventing
      complications in the involutionary period as well as indications and
      contraindications to low-intensity infra-red laser radiation in improving health
      of 40-60-year-old patients.

PMID- 12221845
TI  - [Magnetolaser therapy for patients with acute inflammatory uterine appendages].

PMID- 12221846
TI  - [Comparative analysis of the effect of magnetic fields of varying intensity under
      experimental conditions].
AB  - Three series of experiments on mature male and female non-inbred rats weighing
      160-200 g with chronic vertebrobasilar circulation disorders (CVCD) and chronic
      myeloischemia (CMI) of the lumbosacral segments have been performed to assess
      efficiency of treatment with various physical methods. It was found that
      measurement of ribosomal cystrone activity by bone marrow preparations staining
      with silver salts is a simple and fast method of estimation of cell proliferation
      in the cystrones in exposure to different therapeutic factors, and of prediction
      of the disease outcome. Combined magnetic and electric therapy is more effective
      than monotherapy with sinusoidal modulated currents or modulated currents. This
      is explained by synergism of the therapeutic factors.

PMID- 12221847
TI  - [Medicinal prophylaxis of quantum destruction of cell membranes in magnetolaser
      therapy].

PMID- 12221848
TI  - [Balneologic evaluation of natural brine and mud from the large Iashaltinskya
      lake in the Kalmykiia Republic].

PMID- 12221850
TI  - [Classification of chronic nonspecific cystitis].

PMID- 12221849
TI  - [Rectal suppositories from cacao butter saturated with radon].

PMID- 12221851
TI  - [Classification of chronic prostatitis].

PMID- 12221852
TI  - [Laser therapy of epicondylitis of the shoulder].

PMID- 12221853
TI  - [Comparative effectiveness of using low and superlow frequency magnetotherapy in
      patients with thrombophlebitis and chronic venous insufficiency].

PMID- 12221854
TI  - [Use of "silver key" mineral water in the complex treatment of urolithiasis
      patients].

PMID- 12221855
TI  - [Experience in the recuperative treatment of patients after operations on
      digestive organs in the "Sestoretskiy" sanitorium].

PMID- 12221856
TI  - [Polyneuropathies. Treatment using physical factors].

PMID- 12221857
TI  - [Analysis of the frequency of essential hypertension in the chronobiological
      aspect in an arid zone].

PMID- 12221858
TI  - [Rehabilitation of ischemic heart disease patients after aortocoronary bypass
      using physical factors].

PMID- 12221859
TI  - [Rehabilitation of patients with neurologic manifestations of spinal
      osteochondrosis].

PMID- 12221860
TI  - Chronic urticaria and/or angioedema.

PMID- 12221861
TI  - An overview of chronic urticaria.
AB  - Acknowledging urticaria as a symptom of mast cell degranulation is stressed. The
      biology of the mast cell, and the recognized immunologic and non-immunologic mast
      cell secretagogues are individually discussed along with mechanisms of activation
      and mediators released. The major, preformed mediator histamine in the skin
      produces a prototypic, short-lived urticaria, however, the clinical spectrum and
      pattern of "hives" indicate that other mediators contribute to the polymorphism
      and variable behavior of this symptom. The clinical assessment is almost
      exclusively restricted to the history and physical examination. Features to
      review and examine are presented. The cause of "acute" urticaria is identifiable
      (by history) in the majority of patients, and except for hives that accompany an
      anaphylactic reaction, these patients rarely present to the physician for care.
      The persistent, or "chronic" hiver whose history cannot elicit a cause, is rarely
      triggered by an individual trigger, despite extensive professional evaluation.
      Evidence to support changing the chronological, "acute" and "chronic"
      classification of urticaria to "identifiable" and "non-identifiable" triggered
      urticaria is discussed, as is the futility of extensive, costly laboratory work
      ups. The natural history of urticaria reveals that management should be directed
      toward allowing the patient to maintain an acceptable quality of life (with or
      without some urticaria), until the episode resolves.

PMID- 12221862
TI  - Autoimmune urticaria.
AB  - That a subset of patients with chronic idiopathic urticaria possesses functional
      autoantibodies against the high affinity IgE receptor, or less commonly, IgE, is
      widely accepted. That these same autoantibodies are causative of chronic
      urticaria is highly probable, but not entirely proven, since no animal model of
      chronic urticaria has been devised using these autoantibodies. However we know
      that intradermal injection of anti-FceR1 IgG in healthy volunteers does cause an
      urticarial reaction. The concept of chronic urticaria as a disease caused by
      autoantibodies activating the normal function of target cells (mast cells) by
      combination with a receptor epitope is intriguing, although not entirely unique,
      since a similar mechanism appears to underlie some types of autoimmune
      hyperthyroidism. The detection of patients with these antibodies is usually not
      possible by clinical assessment alone. Unfortunately no convenient or reliable
      immunoassays have been developed to detect the autoantibodies, and the gold
      standard remains the basophil mediator release assay, using normal human donor
      basophils or a basophil leukemia cell line. The autologous serum skin test has
      proved to be a useful screening test for autoimmune urticaria. Identification of
      patients with autoimmune urticaria is of some importance because, apart from
      obviating the necessity for irrelevant tests, immunotherapy, using cyclosporin,
      intravenous immunoglobulin or even plasmapheresis can be contemplated in severely
      affected treatment-resistant patients.

PMID- 12221863
TI  - Evaluating chronic urticaria patients for allergies, infections, or autoimmune
      disorders.
AB  - Urticaria is a common disorder affecting one-fifth of the world's population. The
      pathophysiology is characterized by an increased propensity for mast cell
      degranulation with the release of potent mediators into the dermal and subdermal
      tissues with resulting vasoactive, chemotactic, and inflammatory effects. The
      final clinical manifestation of the typical urticarial lesion is the effect of
      several diverse effects and causes. The general classification is acute, chronic,
      and physical urticaria. In general, allergenic triggers can be identified in
      between 60-80% of acute urticarias. Physical urticarias are characterized by the
      onset after the specific inciting stimulus, which can reproduce the
      characteristic lesion which is usually of shorter duration (with the exception of
      delayed pressure urticaria). Chronic idiopathic urticaria is associated with
      thyroid autoimmunity and, more recently, anti-mast cell receptor antibodies. An
      extensive work-up is usually not indicated or helpful in identifying a cause.
      Food or other allergens are rare causes of this type of presentation. The
      evaluation and work-up is dependent on clues identified by history. The treatment
      is removal of specific and non-specific triggers and the use of symptomatic
      medications generally attenuating the mediator effects.

PMID- 12221864
TI  - Histopathology of chronic urticaria.
AB  - Urticaria of undetermined cause persisting longer than 6 wk is known as chronic
      idiopathic urticaria (CIU). The differential diagnosis of CIU is lengthy and a
      skin biopsy may be of value in making a more precise diagnosis. The
      histopathologic feature that differentiates chronic urticarial lesions from acute
      urticarial lesions is the presence of a mixed cellular perivascular infiltration,
      composed mostly of mononuclear cells, surrounding the dermal postcapillary
      venules. Mast cell numbers in CIU lesions may be increased compared to normal
      dermis. Various patterns of histopathologic findings have been described in CIU.
      An understanding of these patterns of infiltrating cells, mediators, cytokines,
      chemokines and adhesion molecules may provide insight into the mechanism of the
      cutaneous disease and provide valuable information that will help in the
      selection of a more effective therapeutic intervention.

PMID- 12221865
TI  - Urticarial vasculitis.
AB  - Urticarial vasculitis is a clinico-pathologic entity typified by recurrent
      episodes of urticaria that have the histopathologic features of leukocytoclastic
      vasculitis. The cutaneous features may include painful, burning or pruritic skin
      lesions, the persistence of individual lesions greater than 24 hours, palpable
      purpura, pronounced central clearing of lesions, and residual hyperpigmentation
      following resolution. However, because clinical characteristics of urticarial
      vasculitis may overlap with those of allergic urticaria, confirmation of the
      diagnosis requires a lesional skin biopsy. This condition is idiopathic in many
      patients but can also occur in the context of autoimmune disorders, infections,
      drug reactions, or as a paraneoplastic syndrome. In idiopathic urticarial
      vasculitis common laboratory findings are an elevation of erythrocyte
      sedimentation rate and reduction of serum complement. An association between
      urticarial vasculitis and systemic lupus erythematosus has been hypothesized as
      some clinical manifestations of disease overlap and C1q autoantibodies may be
      present in both diseases. Normo-complementemic patients usually have minimal or
      no systemic involvement and often have a better prognosis. On-the-other-hand,
      hypocomplementemic patients have the propensity to have more severe multi-organ
      involvement. Response to treatment is variable and a wide variety of therapeutic
      agents may be efficacious. Initial recommendations for treatment of urticarial
      vasculitis manifest only as non-necrotizing skin lesions include antihistamines,
      dapsone, colchicine, hydroxychloroquine or indomethacin, but corticosteroids are
      often required. With necrotizing skin lesions or visceral involvement,
      corticosteroids are regularly indicated. Cases of severe corticosteroid resistant
      urticarial vasculitis or where corticosteroid morbidity is evident [table: see
      text] may require treatment with other immunosuppressive agents such as
      azathioprine, cyclophosphamide, or cyclosporine.

PMID- 12221867
TI  - Treatment of patients with chronic idiopathic urticaria.
AB  - Treatment of patients with chronic idiopathic urticaria (CIU) involves reducing
      symptoms with the least invasive therapy and carefully balancing risk and
      benefit. The mainstay of therapy is the use of antihistamines with or without the
      use of intermittent pulses of corticosteroids. Alternative therapies to chronic
      corticosteroids include leukotriene antagonists, plasma-phoresis, dapsone,
      stanazolol, hydroxychloroquine, methotrexate, cyclosporin, tacrolimus, and
      warfarin. A practical approach to CIU bases treatment and severity on the
      patients' previous response to therapy. Therapy goals are to reduce symptoms
      until spontaneous resolution occurs. Management of CIU patients can be both
      frustrating and rewarding.

PMID- 12221868
TI  - [Principles of intensive therapy of isolated craniocerebral trauma].

PMID- 12221866
TI  - Angioedema. Pathogenesis, differential diagnosis, and treatment.
AB  - Angioedema is a constellation of syndromes that present a great challenge to the
      clinician. The term "angioedema" describes the localized, transient, episodic
      edema of the deeper layers of the skin or of the mucosa of the gastrointestinal
      tract. Although angioedema may affect any part of the body, the skin and
      gastrointestinal tract are involved most commonly by far. Episodic abdominal pain
      arising from angioedema affecting any intra-abdominal organ may occur without
      skin angioedema; therefore, angioedema must be included in the differential
      diagnosis of intermittent, unexplained abdominal pain. Angioedema is caused by
      extravasation of plasma in the affected areas, which at times is accompanied by
      nonspecific, minimal cellular infiltrate. The most commonly identified causes of
      angioedema are medications, allergens, and physical agents, but most angioedema
      is idiopathic. Rare forms of angioedema associated with either hereditary or
      acquired faulty activation of the complement and kallikrein-kinin systems have
      been extensively described. Taking a comprehensive personal and family history,
      performing a physical examination, and compulsively monitoring the response to
      therapy are the most rewarding and cost-effective diagnostic and treatment tools.
      Diligent and knowledgeable follow-up by the attending physician spares patients
      costly and unnecessary tests as well as harmful treatment. The most effective
      treatment depends on the identification of the causative mechanism and-
      especially when the mechanism is not identified--on the clinician's knowledge and
      experience with innovative therapeutic regimens.

PMID- 12221869
TI  - [Choice of method for anesthesia: is there a problem?].
AB  - Respiratory narcotic devices and monitoring devices have been rapidly improved
      since World War II; new effective and safe drugs and high-quality materials
      appeared. This resulted in a notable decrease of mortality caused by anesthesia:
      from 1 per 50 patients before the war to 1 per 200,000 patients during the last
      years of the twentieth century. Paradoxical as it is, anesthesia today is one of
      the most safe medical specializations. Then what, if not the problem of safety,
      makes anesthesiologists improve the methods of intraoperative protection? It will
      be only just to admit that the main trend in development of anesthesiology today
      is not improvement of its safety, but the desire to make the postoperative period
      as comfortable as possible for the patient and to facilitate anesthesiologist's
      work. The choice of method of anesthesia less and less affects the quality of
      intraoperative protection. Modern methods of total and local anesthesia are so
      universal, that can be used in patients of any age, physical status, in surgery
      of any duration and traumatization. One and the same method can meet the most
      strict requirements to outpatient and venture surgery. Hence, the initially
      rather long list of anesthesiological methods becomes shorter as it should meet
      modern requirements to the efficiency and safety of anesthesia and becomes quite
      short if we take into consideration patient's comfort and physician's
      convenience. The choice from 3-4 methods is completely determined by physician's
      habits or preferences or traditions of the hospital.

PMID- 12221870
TI  - [Treatment of acute pain syndrome].
AB  - The article reviews modern concepts regarding stress response and its effects on
      various organs and systems of critical patients. Postoperative pain is regarded
      with emphasis on its pathophysiology and the prospects of using epidural
      anesthesia-analgesia for alleviating its injurious effects. Analgesia and
      sedation in patients with multiple injuries is discussed. The importance of
      adequate analgesia for alleviation of the injurious effects of nociceptive
      impulses in critical patients is emphasized. Analgesia should be regarded as one
      of the methods of intensive care of critical patients along with respiratory
      support, fluid replacement, and parenteral nutrition.

PMID- 12221871
TI  - [Comparative evaluation of methods for preoperative treatment and variants of
      anesthesia in patient with toxic goiter].
AB  - Surgery on the thyroid has been extensively developing in recent decades. All
      organs and systems are involved in thyrotoxicosis, but cardiovascular involvement
      predominates. We evaluated the preoperative treatment and choice of optimal
      anesthesia for interventions on the thyroid. Preoperative treatment modified the
      central hemodynamic parameters and levels of thyroid and adrenocortical hormones
      in the blood, which should be borne in mind during preparations of patients to
      surgery. Central hemodynamic parameters and hormonal profiles during the
      intervention depended on the variants of preoperative treatment and anesthesia.

PMID- 12221872
TI  - [Liver blood flow during xenon anesthesia in surgical hepatology].
AB  - The authors present their experience gained in anesthesias for resection of the
      liver. Methods for evaluating total liver blood flow by ueveredine dilution,
      portal blood flow by thermodilution, changes in arterial blood supply during and
      after the operation are discussed. Effects of methods of anesthesia on total
      liver blood flow and some parameters of systemic hemodynamics are analyzed.
      Effects of neuroleptanalgesia, ketamine and xenon anesthesia on liver blood flow
      are compared. The efficiencies of anesthesias for resection of the liver and
      their effects on liver function during and after the operation are evaluated. The
      results evidence that disorders in liver circulation parameters were far less
      pronounced in the patients operated on under Xe anesthesia in comparison with
      patients operated on under neuroleptanalgesia and calypsol anesthesia. The study
      confirmed a pronounced analgesic effect of xenon, and clinical results confirmed
      that Xe anesthesia can be used in traumatic interventions.

PMID- 12221873
TI  - [Neurohumoral effect of xenon].
AB  - Clinical trials were carried out in 44 patients during cholecystectomies. The
      patients were divided into 2 groups (22 pts each) receiving (1) Xe:O2 (70:30) or
      (2) N2O:O2 (70:30) + phentanyl (0.1 ml boluses every 20 min). Neurohumoral
      parameters (ACTH, hydrocortisone, STH, prolactin, aldosterone, insulin) were
      almost identically activated in both groups. However, Xe monoanesthesia provided
      an anabolic pattern and better preserved the defense mechanisms of the organism
      in comparison with N2O + phentanyl anesthesia. Moreover, the STH/hydrocortisone
      ratio was 2-fold higher in the Xe group vs. N2O + phentanyl group. The activities
      of thyroid hormones (TSH, T3, T4) fluctuated within the normal range, which was
      indicative of adequate phases of anesthesia in both groups. The parameters of
      central hemodynamics and metabolism also indicated sufficient depth of
      anesthesia.

PMID- 12221874
TI  - [Electroencephalogram, informational saturation of electroencephalogram, and
      bispectral index during xenon anesthesia for laparoscopic operations].
AB  - The depth of xenon anesthesia was never evaluated by modern methods of EEG
      monitoring, and hence, we studied changes in EEG, INEEG, and BIS during different
      stages of xenon narcosis and evaluated the possibility of using these values as
      criteria of xenon anesthesia adequacy. The study was carried out in 60 patients
      during laparoscopic operations on abdominal organs. The patients were divided
      into 2 groups receiving different gas anesthetics (xenon or nitric oxide). The
      results indicate that xenon monoanesthesia caused dose-dependent changes in the
      native and treated EEG; xenon is a good inhalation anesthetic providing adequate
      anesthesia for little traumatic operations even in case of mononarcosis; INEEG
      and BIS monitoring during xenon anesthesia allows an objective evaluation of its
      depth.

PMID- 12221875
TI  - [Central hemodynamics during epidural anesthesia in patients with pyonecrotic
      forms of diabetic foot].
AB  - Central hemodynamics and physiological profiles were followed up during epidural
      anesthesia for surgical treatment of pyonecrotic forms of diabetic foot.
      Modification of epidural anesthesia is described. Hemodynamic stability and
      adequacy of anesthesia in patients with severe concomitant diseases and chronic
      specific complications of diabetes mellitus are demonstrated.

PMID- 12221876
TI  - [European Union of Medical Specialists and professional education of
      specialists].

PMID- 12221877
TI  - [Target control infusion of propofol: is this method really preferable?].
AB  - In order to elucidate the advantages of target control infusion (TCI) over common
      manually controlled infusion, we evaluated the results of 54 anesthesias carried
      out at department of roentgeno-endovascular surgery. All 54 patients received
      intravenous controlled sedation with propofol. The rate of arrest of sedation
      signs after the end of infusion, hemodynamics during anesthesia, comfort for the
      patient, and convenience for the anesthesiologist were evaluated. As regards
      intravenous controlled sedation, we observed no obvious advantages of the TCI
      method for the patient over common manually controlled infusion. Performed by a
      skilled anesthesiologist, both methods ensure sufficient comfort for the patient,
      stable hemodynamics, and easy regulation of the depth of sedation. However, TCI
      is more convenient for physician, and this is the reason why many specialists
      prefer it.

PMID- 12221878
TI  - [Propofol-based protocol of general anesthesia for operations in patients with
      severe burns with ASA class III-IV].
AB  - Use of propofol in surgery on critical patients is limited because of the
      possibility of poorly corrected hypotonia. The effects of total anesthesia with
      propofol + fentanyl + nitric oxide under conditions of artificial ventilation of
      the lungs (tracrium) were evaluated during 63 operations on 42 patients with
      severe burns (ASA III-IV), divided into 2 groups depending on the protocol of
      anesthesia. The difference in the protocols consisted in the method of choice of
      anesthetic doses: in group A we proceeded from EEG data (bispectral index--BIS)
      and in group B relied only on general clinical and hemodynamic signs with a
      retrospective analysis of BIS. Prevention of hemodynamic disorders in both groups
      included infusion loading (7-8 ml/kg), dopamine (5-7 micrograms/kg/min) and
      decrease of the velocity of propofol infusion to 15 mg/kg/h during induction
      anesthesia. This method leveled the hypodynamic effects of propofol. Simultaneous
      monitoring of BIS showed that the propofol dose needed for adequate induction
      narcosis with subsequent intubation should be higher than the dose usually
      recommended for patients with ASA class III-IV. Use of BIS monitoring during the
      operation resulted in a decrease of the propofol and fentanyl doses. The authors
      do not recommend decreasing the velocity of propofol infusion below 3 mg/kg/h (at
      FiN2) = 0.6) because of the risk of awakening during narcosis.

PMID- 12221879
TI  - [Clofelin in the regimen of intravenous anesthesia during surgery for severe
      burns].
AB  - The data on clofelin effect on the course of total anesthesia are contradictory.
      Clofelin effect on hemodynamics, drug doses, depth of anesthesia, and time of
      awakening after surgery was studied in 28 male patients with extensive deep
      thermal injuries in a state of acute burn toxemia and septicotoxemia. Randomized
      double blind study was carried out in 2 groups: study group, in which clofelin
      was injected intravenously (2.6 +/- 0.15 micrograms/kg) before induction to
      anesthesia and placebo group (0.9% NaCl, 20.0). Similar operations were carried
      out in both groups: debridement of burn wounds with autodermoplasty on body
      surface of different area. Methods of anesthesia were similar in both groups:
      premedication with reladorm at night and phenasepam before surgery; induction
      with phentanyl and thiopental and laryngeal mask installation; maintenance
      anesthesia with midasolam, thiopental, fentanyl, tracrium, and artificial
      ventilation of the lungs. The following parameters were recorded: hemodynamic
      (HR, ADsys, dia, mean); EEG (bispectral index--BIS, 95% right spectrum frequency-
      SEF-95). Drug consumption, volume of infusions, blood loss, and time of awakening
      were recorded. The authors failed to detect pronounced analgesic and sedative
      effects, which are assigned to clofelin, after its single use in the above
      mentioned dose, but noted its obvious stabilizing effect on hemodynamics, which
      persisted for up to 1.5 h after injection. Clofelin is recommended to be used in
      a dose of 2.5 micrograms/kg 10-15 min before induction in patients with burns
      with hyperdynamic circulation.

PMID- 12221880
TI  - [Diprivan-EDTA--choice in favor of patients safety].
AB  - Use of propofol in anesthesiology increases with every year. On the other hand,
      some data indicate a risk of postoperative complications caused by bacterial
      contamination of propofol solution in the course of its utilization. The
      probability of these complications reaches 6.3%. A modified formula of propofol
      (diprivan-EDTA) has been developed, which is characterized by antibacterial
      (bacteriostatic) effect towards 20 most prevalent microorganisms. Preliminary
      results of clinical evaluation of diprivan-EDTA safety indicate its positive
      effect on the incidence of severe postoperative complications and mortality of
      patients in intensive care wards.

PMID- 12221881
TI  - [Choice of optimal ventilation maintenance].
AB  - Twenty-nine angiosurgical patients with disordered ventilation-perfusion
      correlations were examined. Effects of CMV (controlled mechanical ventilation) +
      PEEP (positive end expiratory pressure) and IRV (inverse ratio of ventilation) on
      gas exchange and hemodynamics of the lungs were studied. Gas exchange improved in
      all patients, but sooner in the CMV + PEEP group. CI increase was more pronounced
      in the IRV group.

PMID- 12221882
TI  - [Effect of hyperventilation on the cerebral blood flow and metabolism in patients
      with craniocerebral trauma].
AB  - Cerebral blood flow and metabolism were studied in 44 patients with acute severe
      craniocerebral injuries (contusions of the brain and removal of intracranial
      hematomas) with consciousness depression (moderate coma), hospitalized in
      intensive neurological care wards. Oxygen supply to the brain was repeatedly
      evaluated (acid-base status of the jugular vein blood, oxygen arterio-venous
      difference, oxygen extraction coefficient), oxymetry of the brain was repeatedly
      carried out, and vital functions were monitored over the entire period of
      disease. Cerebral blood flow was monitored by rheoencephalography, which helped
      timely detect the changes in cerebral blood flow in patients with craniocerebral
      injuries during different ventilation protocols used in intensive care. All
      studies were carried out during three stages: 1) initial stage, when the patients
      were brought to intensive neurological care wards after surgical intervention,
      and during normoventilation (paCO2 36-40 mm Hg; 2) moderate hyperventilation
      (paCO2 35-26 mm Hg); and 3) pronounced hyperventilation (paCO2 25-20 mm Hg).
      Specific changes in the cerebral blood flow during the acute period of
      craniocerebral injury were detected during different ventilation regimens in 2
      groups of patients: group 1 with lethal outcomes and group 2 with positive
      changes.

PMID- 12221883
TI  - [Evaluation of the clinical status of patients with surgical infection].
AB  - The possibility of objectively evaluating the severity of the clinical status of
      patients with surgical infection is discussed. A retrospective and prospective
      analysis of clinical laboratory values is carried out in 196 patients with
      surgical sepsis. SAPS score indicated a statistically significant difference in
      the state of two groups of patients (survivors and dead). Analysis of clinical
      laboratory data offers additional criteria, specific of surgical infection, which
      improved the accuracy of scoring evaluation.

PMID- 12221884
TI  - [Correction of hemodynamics in elderly and aged patients after bile duct
      operation].

PMID- 12221885
TI  - [Study of immunodepressive and allergic effects of xenon].
AB  - Experimental studies on mice showed that after four 30-min and 60-min inhalations
      of Xe:O2 (80:20) during 2 weeks, weight indexes of the lymphoid organs (spleen
      and thymus) increased, phagocytic activity did not change, and primary immune
      response was moderately stimulated. This indicates that xenon exerted no
      immunotoxic effects and can be used in patients with diseases associated with
      primary immunodeficiency. Study of allergic effects on albino guinea pigs showed
      that on days 14 and 21 of sensitization xenon in the resolving dose possessed no
      anaphylactogenic activity, caused no specific lysis of leukocytes, and did not
      modulate the counts of basophils and eosinophils. Xenon did not induce allergic
      reactions and is not a potential allergen, which is important in patients with
      panallergy.

PMID- 12221886
TI  - [Case report of acute brain edema treated with active venous shunting].

PMID- 12221887
TI  - [Effect of regional anesthesia on hemodynamics in patients without lower limbs].

PMID- 12221888
TI  - [Organisation of anesthesiology and intensive care services in Russian Federation
      (trends of development)].

PMID- 12221889
TI  - The allergy-asthma connection.
AB  - Asthma and allergic rhinitis are both common conditions and, therefore, often
      present in the same patients. Also, among the various triggers for asthma,
      allergy is an extremely common provoking factor for both adult and pediatric
      patients. The nose and lungs are connected by neural reflexes, and nasal allergen
      provocation can cause bronchoconstriction, and bronchial challenge can result in
      nasal inflammation. Treatment of allergic rhinitis with nasal steroids improves
      asthma control of symptoms, decreases bronchial hyperreactivity, and improves
      forced expiratory volume in 1 second. Treatment of subjects who have both
      allergic rhinitis and asthma with antihistamines (both alone and in combination
      with decongestants) and/or leukotriene receptor antagonists results in
      improvements in both conditions.

PMID- 12221890
TI  - Medical and economic dimensions linking allergic rhinitis and asthma.
AB  - Allergic rhinitis and asthma are two of the most common chronic conditions
      affecting the population. There has been a growing understanding of the link
      between these disorders as they commonly occur in the same individual, of their
      relationship with allergies, and of the total economic impact in both direct and
      indirect costs associated with these maladies. For physicians caring for these
      patients, an understanding of the relationship of these conditions and the
      magnitude of health care costs is paramount in proper treatment.

PMID- 12221891
TI  - Viral infection and allergy: lower airway.
AB  - Acute asthma exacerbations in adults and children are triggered commonly by viral
      upper respiratory infections. The main culprits are respiratory syncytial virus
      and parainfluenza virus in young children and rhinovirus in older children and
      adults. Recent investigations in multiple laboratories have increased our
      understanding of the nature of this relationship. Postulated mechanisms include a
      viral modulation of airway epithelial and inflammatory cell function with the
      release of proinflammatory cytokines and mediators, airway microvascular
      endothelial cell function leading to airway wall edema, airway smooth muscle cell
      functions, and neural regulation of airway tone via either enhanced
      parasympathetic efferent neuronal activity, activation of the release of
      bronchoactive neuropeptides from sensory c-fibers in the airways, or modulation
      of the influence of the nonadrenergic/noncholinergic neuronal system on airway
      tone. There also is evidence that rhinoviruses may directly infect the lower
      airways. These potential mechanisms likely relate to, are superimposed on, and
      potentiate preexisting inflammatory and immune responses that are characteristic
      of the atopic asthmatic airway. Undoubtedly, future efforts will be aimed at the
      prevention of asthma exacerbations via well-targeted and well-conceived
      strategies for prevention and/or treatment of upper respiratory infections.

PMID- 12221892
TI  - The role of small airway inflammation in asthma.
AB  - Although inflammation in the large central airways has been the subject of
      numerous asthma studies, inflammation in the small distal airways remained
      largely unexamined because of the relative inaccessibility of these structures.
      However, fiberoptic bronchoscopy, combining endobronchial and transbronchial
      biopsy, now allows specimens to be obtained from both proximal and distal areas
      of the lung. Newly refined morphometric and immunocytochemical techniques have
      been applied to both autopsy and lung biopsy specimens. Together, these
      technological changes have had a profound impact on the study of small airway
      inflammation. Now, it is understood that the asthma-associated inflammation
      evident in the large airways occurs in the distal airways as well. The
      inflammatory process in the two regions has related features: infiltrates contain
      activated T lymphocytes and eosinophils, increased mucus plugging, and smooth
      muscle hyperplasia can be observed. Although the similarities are pronounced,
      inflammation in the small airways differs in important ways from large airway
      inflammation. The eosinophilic infiltration that occurs throughout the asthmatic
      lung also is active in the small airways. The contribution of small airway
      inflammation to deficits in pulmonary function has been clarified by thoracic
      high-resolution computed tomography imaging. Results of such imaging suggest that
      the distal airways are a major site of airway obstruction in patients with asthma
      and may play a significant role in airway hyperresponsiveness; both disorders are
      cardinal features of asthma. In addition, functional bronchoscopic studies of the
      small airways in asthma patients have found high peripheral airflow resistance,
      even when lung function appears normal. Current formulations of inhaled anti
      inflammatory medications, particularly corticosteroids administered by metered
      dose inhalers using chlorofluorocarbon propellants, treat the proximal airways
      more effectively than the distal airways. However, some new formulations of
      inhaled steroids that utilize hydrofluoroalkane propellants produce aerosols of
      smaller average particle size, with greater penetration into the peripheral
      airways. Their potential to treat inflammation at peripheral sites may account
      for the significant improvements in asthma outcomes that have been reported in
      clinical trials of these new formulations.

PMID- 12221893
TI  - Combination therapy and new directions for managing atopic dermatitis.
AB  - Atopic dermatitis is a common skin disease with a complex immunopathology that
      has a significant impact on the quality of life of patients and their families.
      Although topical corticosteroids have been the cornerstone of therapy, safety
      concerns, especially in children, with potent preparations or with chronic use
      have prompted treatment with various adjunctive therapies. Recently, topical
      calcineurin inhibitors, including tacrolimus and pimecrolimus, have been shown
      effective as monotherapy for this chronic relapsing disease.

PMID- 12221894
TI  - Asthma pathophysiology and the scientific rationale for combination therapy.
AB  - The clinical and scientific description of asthma has been undergoing an
      evolution of continuous revision during the past 10 years. This disorder has been
      recognized as a complex entity with interplay between genetic, environmental, and
      allergenic factors resulting in a significant component of inflammation of the
      airway. Recent directions in therapy differ in taking either the broad-based
      antagonist or the specific mediator antagonist approach. This review highlights
      some of the scientific evidence of the operative pathophysiological events and
      reviews their applicability to the rationale for broad-based combination asthma
      therapy.

PMID- 12221895
TI  - Hypersensitivity to common tree pollens in New York City patients.
AB  - Testing for tree pollen hypersensitivity typically requires the use of several
      tree pollens. Identifying patterns of cross-sensitivity to tree pollens could
      reduce the number of trees used for testing. The goal of this study was to relate
      reported tree pollen levels to hypersensitivity patterns. Three hundred seventy
      one allergy patients were tested serologically for hypersensitivity toward
      prevalent tree pollens in the surrounding New York area over the years 1993-2000.
      Specific tree pollens that were examined included oak (Quercus alba), birch
      (Betula verrucosa), beech (Fagus grandifolia), poplar (Populus deltoides), maple
      (Acer negundo), ash (Fraxinus americana), hickory (Carya pecan), and elm (Ulmus
      americana). Statistical analysis of the levels of hypersensitivity was performed
      to identify correlations and grouping factors. Pollen levels, obtained from
      published annual pollen and spore reports, were characterized and related to the
      prevalence of hypersensitivity for the various trees. The highest prevalence of
      hypersensitivity (score > or = class 1) was for oak (34.3%), birch (32.9%), and
      maple (32.8%) tree pollens. Lower prevalences were observed for beech (29.6%),
      hickory (27.1%), ash (26%), elm (24.6%), and poplar (20.6%) trees. Significant
      correlations were observed between oak, birch, and beech radioallergosorbent test
      scores. Factor analysis identified two independent pollen groups with oak, birch,
      and beech consisting of one group and the other five tree pollens constituting
      the other group. Peak pollen counts clearly were highest for oak, birch, and
      maple trees. The peak pollen counts corresponded roughly to seropositivity
      prevalences for the tree pollens. When elm, poplar, and beech test scores were
      not used to identify patients who were allergic to tree pollens, only 1 of 106
      patients with any positive tree radioallergosorbent test score was missed. It is
      concluded that in the New York City area, hypersensitivity to tree pollens most
      often is manifested with allergy to oak, birch, and maple tree pollens.
      Identifying beech, poplar, and elm hypersensitivity adds little toward
      identifying patients who are allergic to tree pollens. This may relate in part to
      cross-reactive epitopes. These data suggest that these three trees can be
      eliminated from testing with only a < 1% loss of sensitivity.

PMID- 12221896
TI  - Relief of sinus pain and pressure with fluticasone propionate aqueous nasal
      spray: a placebo-controlled trial in patients with allergic rhinitis.
AB  - Although allergic rhinitis is commonly associated most with symptoms of nasal
      congestion, rhinorrhea, sneezing, and itching, the symptom of sinus pain and
      pressure often prompts the patient to seek medical attention. The effect of
      fluticasone propionate on this symptom has not been studied. The purpose of this
      study was to compare the efficacy and safety of fluticasone propionate aqueous
      nasal spray to placebo vehicle in the treatment of patients with sinus pain and
      pressure arising from allergic rhinitis. A multicenter, double-blind, parallel
      group trial was conducted in 206 symptomatic patients > or = 12 years with
      seasonal or perennial allergic rhinitis. Patients were treated for 14 days with
      either fluticasone propionate aqueous nasal spray, 200 mcg once daily, or placebo
      vehicle. Patients attended clinic visits and kept diary cards rating sinus pain
      and pressure (measured as one symptom) and nasal congestion symptoms during the
      study. Treatment with fluticasone propionate provided significantly greater
      relief of symptoms of sinus pain and pressure compared with placebo over the
      entire 14-day treatment period. Nasal congestion scores also were significantly
      reduced compared with placebo at each time point. Treatments were well tolerated,
      and the incidence of adverse events attributable to study treatments was similar
      between groups. Our data indicate that symptoms of sinus pain and pressure and
      nasal congestion can be significantly reduced in patients with allergic rhinitis
      when treated with fluticasone propionate aqueous nasal spray, 200 mcg once daily.

PMID- 12221898
TI  - Hot tub-related Mycobacterium avium intracellulare pneumonitis.
AB  - Atypical Mycobacteria have been widely known to cause opportunistic infections in
      patients with AIDS. Recently, cases have been reported of patients colonized with
      atypical Mycobacteria who are only partially responsive to antibacterial
      treatment. It is thought that perhaps these cases represent a clinically
      different subset of patients that not only have underlying infection, but
      hypersensitivity disease as well, which may be responsive to concomitant
      treatment with oral corticosteroids.

PMID- 12221897
TI  - Long-term evaluation of hypersensitivity pneumonitis: a case study follow-up and
      literature review.
AB  - This study reports a 3-year follow-up of a classic presentation of
      hypersensitivity pneumonitis (HP), originally reported elsewhere, after removal
      of the causative antigens. The literature is reviewed and this case is compared
      with outcomes of series previously reported. The patient was reevaluated by
      clinical, serologic, radiographic, and pulmonary function testing 3 years after
      removal of her home's contaminated humidifier, cleaning of the home, and
      administration of a course of prednisone. Repeat serologic measurements revealed
      positive serum precipitins only for Aspergillus flavus and Phoma herbarum,
      significantly fewer than her original panel, which revealed precipitating
      antibodies to her humidifier water and 10 other specific antigens. Pulmonary
      function tests remained stable. Physical exam revealed bibasilar rales. Computed
      tomography scan revealed pulmonary fibrosis, bronchiectasis, and honeycombing
      that was compared with 3 years earlier. Although most of the data obtained on
      reevaluation suggest remission, radiographic findings have not remitted. Long
      term follow-up of parameters of HP disease activity do not always reveal
      consistent findings. This patient appears to be in a category of HP between the
      classic subacute and chronic stages.

PMID- 12221899
TI  - Organ donor with cerebellar medulloblastoma: a case report and review of the
      literature.
AB  - Transplantation of organs and tissues procured from brain-dead organ donor (BDOD)
      is nowadays a common and desirable therapy for end-stag organ failure, especially
      kidneys, liver and heart. The majority of organs for transplantation are obtained
      from individuals with massive and irreversible central nervous system injury.
      This group of organ donors is however unsatisfactory and small according to
      needs. Significant percentage of multiorgan donors could be found among patients
      suffering from primary cerebral neoplasms as these rarely metastasize
      spontaneously outside the central nervous system. The paper presents the case of
      a 30-year-old male donor with a central nervous system tumor. Histogenesis,
      pathway of malignant dissemination, prognosis and the use of organ donor with
      cerebellar medulloblastoma are also discussed.

PMID- 12221900
TI  - Aneurysm of common and internal iliac arteries 14 years after kidney
      transplantation--a case report.
AB  - The aim of the report is to present successful surgical treatment of aneurysm of
      common iliac artery (CIA) and internal iliac artery (IIA) in a kidney transplant
      patient. The aneurysm of CIA and IIA, causing arterial hypertension, was
      diagnosed and treated surgically in a 47-year-old male patient, who had received
      a cadaveric kidney transplant 14 years before. During the operation, consisting
      of aorto-femoral unilateral grafting with transplanted kidney artery implantation
      to the side of the graft and aneurysm exclusion, cold Ringer's lactate perfusion
      was used to protect the transplanted kidney. There were no postoperative
      complications; the transplant function is satisfactory in a follow-up of 44
      months. Exclusion of CIA and IIA aneurysm using aorto-femoral unilateral graft is
      an effective way of treatment in kidney transplant patients. The cold perfusion
      during aortic cross-clamping is an effective and simple method of transplanted
      kidney protection.

PMID- 12221901
TI  - Thrombotic microangiopathy in renal transplantation.
AB  - The term thrombotic microangiopathy (TMA) encompasses syndromes of
      thrombocytopenia, microangiopathic haemolytic anaemia, neurologic deficits, renal
      dysfunction and variable signs of organ impairment. Childhood cases of TMA with
      predominant renal failure are usually referred as Haemolytic Uremic Syndrome
      (HUS), and adult cases with major neurological involvement as Thrombotic
      Thrombocytopenic Purpura (TTP). Exotoxins, produced in most cases by E. Coli O
      157:H7, have been related to diarrhea associated HUS(D + HUS). Anticancer
      (mitomycin), immunosuppressive drugs (cyclosporin, tacrolimus and OKT3) and as
      well as some antiplatelet agents (ticlopidine, clopidrogel) have been associated
      with both HUS and TTP. Defective factor H or vWF protease activity have been
      found with familiar and recurrent forms. Endothelial damage and dysfunction is
      most likely the initial event of the pathogenic process that eventually leads to
      platelet aggregation, microvascular thrombosis and tissue ischemia. TMA may occur
      de novo in the native kidneys of patients who received a non-kidney transplant or
      in the transplanted kidney of patients who progressed to ESRD because of a
      disease other than HUS. Calcineurin inhibitors and vascular rejection are most
      often involved in these cases. The disease may also recur on the transplanted
      kidney in patients who progressed to ESRD because of HUS/TTP. The risk of
      postransplant recurrence is negligible for D + HUS but is close to 100% in
      familial/recurrent forms associated with low C3 and decreased factor H
      bioavailability or activity. Withdrawal or treatment of precipitating factors are
      the most effective approach. Plasma therapy is usually attempted with the
      rationale to limit the microangiopathic process, but its efficacy for improving
      graft survival is unproven. The outcome of recurrent forms is almost invariably
      poor.

PMID- 12221902
TI  - Fibrinolysis in chronic renal failure, dialysis and renal transplantation.
AB  - The best known function of the fibrinolytic system is its ability to dissolve
      blood clots. The key enzyme of fibrinolysis, plasmin, is formed by conversion
      from plasminogen through the action of activators, the most important of which is
      tissue type plasminogen activator (tPA). Low levels of tPA or excessive levels of
      plasminogen activator inhibitor-I (PAI-I) cause hypofibrinolysis, causally
      related to the development of atherosclerosis and associated thrombotic
      complications, as well as with the development of venous and arterial thrombosis.
      A chronic decrease in renal function leads to hypofibrinolysis due primarily to
      low levels of tPA. Hypofibrinolysis is present both in patients treated by long
      term hemodialysis and by peritoneal dialysis. The hemodialysis procedure acutely
      raises the plasma levels of tPA, primarily as a result of the bioincompatibility
      of materials in the extracorporeal circuit. In peritoneal dialysis, dialysis
      solution dwell time is associated with an increase in PAI-I levels in the
      abdominal cavity. Fibrinolysis defects occur also in renal transplant recipients.
      In transplant patients, the main abnormality is also hypofibrinolysis which,
      however, unlike the situation with the other methods of renal replacement
      therapy, is secondary to a rise in PAI-I. A role in the increase of the plasma
      levels of PAI-I in transplant patients is played by steroid- and cyclosporine
      based immunosuppression, most likely by metabolic disorders such as insulin
      resistance or dyslipoproteinemia, and by genetic factors. Animal experiments with
      chronic rejection have shown abnormalities in local fibrinolysis in the graft,
      particularly increased PAI-I expression. Fibrinolysis defects may contribute to
      an early and frequent development of atherosclerosis in patients with chronic
      renal failure, to chronic dysfunction of the renal transplant, or to peritoneal
      fibrosis and peritoneal catheter obstruction in patients on peritoneal dialysis.
      The exact role of hypofibrinolysis in the development of these complications, and
      the potential for modulating it, warrant further research.

PMID- 12221903
TI  - The effect of chronic allograft rejection on plasma regulators of fibrinolysis.
AB  - Chronic renal allograft rejection is often associated with the presence of fibrin
      thrombi in the microcirculation. Our purpose was to evaluate the influence of
      chronic rejection on fibrinolytic regulators in plasma of renal allograft
      recipients. We evaluated the concentration and activities of tPA, uPA and PAI-I
      in plasma from kidney allograft recipients. We studied 64 patients who underwent
      kidney transplantation from cadaveric allograft donors. At the time of the study
      38 patients had stable graft function for at least 6 months proceeding the study,
      and 26 recipients had biopsy-proven chronic rejection of the kidney transplant.
      Control group included 30 healthy blood donors. In kidney transplant recipients
      we found significantly higher plasma tPA activity (median: 0.99 IU/ml; range: 0
      3.8 IU/ml) in comparison to healthy controls (median: 0.15 IU/ml; range: 0-2.8
      IU/ml) (p = 0.002) as well as significantly lower plasma PAI-I activity (median:
      7.06 U/ml; range: 0-33.2 U/ml) in comparison to healthy controls (median: 21.8
      U/ml; range: 0-36.7 U/ml), (p = 0.0001). Among transplant recipients, PAI-I
      plasma activity in recipients with chronic graft rejection (median: 10.16 U/ml;
      range: 0-33.2 U/ml) was significantly higher than in patients with stable graft
      function (median: 4.83 U/ml; range: 0-22.9 U/ml), (p = 0.01). In transplant
      recipients with stable graft function and poorly controlled hypertension we found
      significantly higher PAI-I plasma activity in comparison to recipients with
      normal blood pressure (p = 0.006). In kidney transplant recipients there was a
      positive correlation between the dose of prednisone and PAI-I activity in plasma
      (p = 0.01) and an association between BMI value and plasma PAI-I activity (p =
      0.008), as well as an association between BMI value and plasma tPA-Ant
      concentration (p = 0.006). Among transplant recipients, patients treated with ACE
      inhibitors had significantly lower uPA plasma activity than the rest of the group
      (p = 0.003). In recipients with stable graft function we found a correlation
      between CsA concentration and tPA activity (p = 0.04), as well as an association
      between the dose of CsA and uPA-Ant concentration in plasma (p = 0.049). In
      patients with chronic graft rejection we found a negative correlation between the
      dose of prednisone and uPA-Ant plasma level (p = 0.004). Renal allograft
      recipients have higher tPA and lower PAI-I activities in plasma in comparison to
      healthy individuals. Chronic allograft rejection, is as well as poorly controlled
      hypertension, seem to be associated with an increase PAI-I plasma activity. In
      kidney graft recipients there is a relation between the value of BMI and the
      activity and concentration of tPA-Ant as well as the value of BMI and the PAI-I
      activity in plasma. Poorly controlled hypertension is associated with an increase
      in PAI-I plasma activity. The results of our study suggest a stimulatory effect
      of CsA on tPA and PAI-I plasma activities as well as on uPA-Ant concentration,
      while prednisone in turn seems to enhance PAI-I activity in plasma and decrease
      uPA expression. In renal allograft recipients ACE inhibitors seem to reduce uPA
      plasma activity.

PMID- 12221905
TI  - Effects of immunosuppressive drugs on platelet aggregation in vitro.
AB  - Disturbances in platelet functions are found in kidney diseases and may
      contribute to the progression of atherosclerosis with its thrombotic
      complications. Kidney allograft recipients are particularly prone to dyslipidemia
      and have a high risk of cardiovascular death. The purpose of this work was to
      assess effects of various immunosuppressive drugs on aggregation of platelets
      obtained from healthy volunteers and chronically hemodialyzed patients. Platelet
      aggregation in the whole blood and in PRP was induced by collagen (2-microgram/ml
      whole blood and PRP) arachidonic acid (0.75 mM whole blood and PRP), ADP (10
      microM--whole blood and 5 microM--PRP), ristocetin (0.75 mg/ml--whole blood and
      1.5 mg/ml--PRP) and was studied after preincubation with clinically relevant
      concentrations of cyclosporine A, FK 506, 15-deoxyspergualin, azathioprine,
      mizoribine, mycophenolic acid and mycophenolate mofetil. Preincubation with
      cyclosporine A resulted in a significant increase in platelet aggregation,
      whereas preincubation with FK 506, azathioprine, mizoribine, mycophenolic acid
      and mycophenolate mofetil caused a decrease in platelet aggregation. 15
      deoxyspergualin did not affect platelet aggregation. Enhanced platelet
      aggregation in CSA-treated kidney allograft recipients may have clinical
      implications in regard to the reported tendency to thrombosis in those patients,
      and to CSA-induced nephrotoxicity. Thus, inhibition of platelet activity in these
      patients might be of clinical benefit.

PMID- 12221904
TI  - Effects of fluvastatin on homocysteine and serum lipids in kidney allograft
      recipients.
AB  - Hyperhomocysteinemia is now recognized as an independent risk factor for
      atherosclerotic cardiovascular disease in patients with normal renal function.
      Hyperhomocysteinemia is common in patients with chronic renal failure. Kidney
      transplant recipients have a high risk of cardiovascular death. Recently,
      attention has been paid to the association between homocysteine and
      cardiovascular disease. Dyslipidemia is also common in kidney transplant
      recipients. The purpose of this study was to assess whether fluvastatin in a dose
      of 20 mg affects homocysteine concentration in 10 stable renal transplant
      recipients. We evaluated Hcy, lipoprotein (a) by the use of commercially
      available kits as well as plasma fibrinogen and cholesterol, triglycerides and
      albumin levels. All the parameters were studied before and after 1, 2 and 3
      months of fluvastatin treatment. Cholesterol and LDL decreased significantly as
      early as after 1 month and remained lowered during the therapy. No significant
      changes in Hcy, lipoprotein (a) and fibrinogen were found during therapy with
      fluvastatin. Fluvastatin is an effective hypolipemic agent and has no effect on
      Hcy and fibrinogen concentration in kidney transplant recipients.

PMID- 12221906
TI  - Critical overview of the current status of organ donors with primary central
      nervous system tumors.
AB  - The transmission of donor-related malignancies by organ transplantation is rare
      event but biological behaviour of malignant tumors developed by the transplanted
      patients is in general more aggressive than similar ones in non-transplanted
      population. This paper presents an analysis of our series of cases and a review
      of the literature to the point of the transmission of cancer from organ donors
      with primary central nervous system tumors. Patients with primary CNS neoplasms
      have been accepted for organ donation because these tumors very rarely spread
      outside the CNS. To our knowledge, after an extensive review of the literature,
      the CNS tumor transmission risk with transplantation may be estimated between a
      little more than 0% and 3%. In the light of available data and in accordance with
      our investigations we consider that patients with CNS tumors can be accepted as
      donors as long as the risk of dying on the waiting lists is significantly higher
      than the tumor transferral risk. Organ donors with benign or low-grade CNS tumor
      should be accepted unreservedly. Donors with high-grade tumors should be consider
      as "marginal donors" and their assessment can be based on the comparison and the
      balance between the risk of tumor transmission and the medical condition of the
      recipient.

PMID- 12221907
TI  - [Effect of sociocultural factors on maternal and perinatal morbidity with or
      without mortality among adolescents seen in 3 states of the Mexican Republic].
AB  - This study was aimed on comparing the degree of association between social
      cultural factors and maternal or perinatal morbidity and/or mortality of the
      adolescent. A paired case-control study was designed with adolescent in puerperal
      immediate stage affiliated to the Mexican Institute of Social Security from
      Tabasco, Tlaxcala and Northern Veracruz, that were adjusted to the selection
      criteria of the sample, between June of 1998 and February of 1999. Two groups
      were integrated, cases, with adolescent in puerperal immediate stage affected
      (with maternal or perinatal morbidity and/or mortality) and controls, with
      adolescent not affected in puerperal immediate stage. Information concerned to
      biological and social-cultural risk factors from each subject was obtained
      applying a validated survey (EFRASEMA 1) and checking their clinical file, whose
      information was poured in a database (EFRASEMA 2). Interviewers did not know the
      outcome of the study, which in turn assured the blindness of the information.
      Once data was obtained, subjects were assigned to each group of study. Matching
      factors were age, nutritional status, intergenesic interval and previous
      pregnancy systemic pathology. Proportion of subjects, cases and controls; with or
      without social-cultural risk factors was determined. The risk of maternal or
      perinatal morbidity and/or mortality in the exposed subjects was estimated by
      odds ratio (OR) and the differences inferred through Mantel and Haenszel chi 2
      and Fisher's exact tests (confidence intervals alpha = 0.05 and beta = 0.2).
      There was a sample of 486 subject, 44 were eliminated due to insufficient data.
      Studied population was integrated finally with 221 cases and 221 paired controls
      1: 1. 71.950% of participants were married, 22.62% in free union, 4.98% single
      and 0.45% separate, average global age was 17.98 +/- 1.39 years. The inferential
      analysis showed an OR 0.64 (Cornfield 95% confidence limits: 0.40 < OR < 1.03, p
      = 0.0510600) concerning desired pregnancy in favor to controls. Appropriate
      reproductive information had an OR = 0.34 (Cornfield 95% confidence limits: 0.21
      < OR < 0.54 p = 0.0000014). Ideal cumulated fertility offered an OR 0.62
      (Cornfield 95% confidence limits: 0.39 < OR < 0.98, p = 0.0298500). These results
      show an association between the social-cultural factors and the presence of
      maternal or perinatal morbidity and/or mortality in the studied adolescents.
      Desired pregnancy, appropriate reproductive information and ideal cumulated
      fertility are protection factors to maternal or perinatal morbidity and/or
      mortality.

PMID- 12221908
TI  - [The HELPP syndrome--evidence of a possible systemic inflammatory response in pre
      eclampsia?].
AB  - INTRODUCTION: The principal causes of morbidity and mortality during pregnancy in
      Mexico, are preeclampsia/eclampsia, obstetric hemorrhage and puerperium
      complications; this is, 62% of maternal deaths in last years. HELLP syndrome was
      observed between 5 to 25% of the mortality in pregnancies of 36 weeks or less.
      OBJECTIVE: To analyze patients with HELLP syndrome in ICU's (Intensive Care Unit)
      of a Gynecology and Obstetric Hospital, related to the abnormal hematological,
      hepatic and renal results with the obstetric case history and the clinical
      complications. MATERIALS AND METHODS: A transversal study in patients with HELLP
      syndrome during 1998 and 1999 were carry out. CASE DEFINITION: Peripheral blood
      with Microangiopathic hemolysis, elevated liver enzymes: AST, ALT over 40 UI/L,
      even when were LDH lower than 600 UI/L. It was evaluated the hepatic and renal
      function, platelets count, microangiopathic hemolysis, arterial pressure,
      seizures, icteric skin color, blindness, visual disturbances, nausea, vomiting
      and upper quadrant right abdominal pain. In newborn we analyzed gestational age,
      sex, weight and APGAR. We studied for an association between maternal and
      biochemical variables with Correlation Pearson Test, and dependence between
      variables with lineal regression model. RESULTS: 2878 patients with hypertensives
      disorders in pregnancy (11.64%). The 1.15% (n = 33) had HELLP syndrome with
      specific maternal mortality of 0.4 per 10,000 live birth, perinatal mortality of
      1.62 per 10,000 live birth; and renal damage in 84.5%. Coefficient beta was
      higher between number of pregnancies to platelets count (-0.33) and creatinine
      clearance (-0.401). CONCLUSION: We found an important renal damage, low
      platelets, elevated liver enzymes in women with two or more pregnancies. Then we
      propose there are similarities between HELLP syndrome and Systemic Inflammatory
      Response Syndrome (SIRS) because they could have the same pathophysiology.

PMID- 12221909
TI  - [Prevalence and risk factors associated with intestinal parasitoses in pregnant
      women and their relation to the infant's birth weight].
AB  - OBJECTIVE: To determine the prevalence and the risk factors associated with
      intestinal parasitosis in pregnant women and the relation with the newborns.
      MATERIAL AND METHODS: A transversal analytical study. 207 women were selected and
      a guided survey was applied. They were also asked for three stool samples for
      their parasitoscopic study by Faust's method. The levels of hemoglobin as well as
      the child's birth weight. RESULTS: The prevalence of intestinal parasitosis was
      38.2%. 84% of the women presented only one parasite. The protozoan Giardia
      lamblia was very frequent (65.8%), followed by Ascaris lumbricoides (13.9%).
      Women with positive samples in the parasitoscopic study were younger (p = 0.002),
      and a greater probability of a scholastic level lower than Jr. High School, as
      well as having a dirt floor in their house and a positive contact with domestic
      animals. The mean weight of the newborn of mothers without intestinal parasitosis
      was 3,333 +/- 441 g; in the group of mothers with only one parasite was 3,291 +/-
      360 g; with two parasites 3,104 +/- 425 g; and three parasites the weight was
      2,675 +/- 674 g, these differences were not statistically significant (P = 0.1),
      however, there is a greater possibility of a newborn with less weight at birth
      than expected. CONCLUSIONS: The prevalence of intestinal parasitosis in pregnant
      women is high due to their physiological state. It is necessary to modify some
      preventive measures of information, education and to give specific treatment
      before the pregnancy in order to increase some of the pregnant women's health
      indicators. The newborn of mothers with intestinal parasitosis have a greater
      probability of being born with less weight than what is expected.

PMID- 12221910
TI  - [Polymorphism in codon 72 of the p53 gene and cervico-uterine cancer risk in
      Mexico].
AB  - A polymorphism at codon 72 in the p53 gen has been reported as a potential risk
      factor to cervical cancer (CC) because human papillomavirus (HPV) is more
      effective at degrading p53 Arg-72 than p53 Pro-72, making individuals homozygous
      for p53 Arg-72 seven times more likely to develop HPV-associated CC. As In Mexico
      the CC is a health public problem, we designed this study to determinate whether
      the p53 codon 72 polymorphism represent a risk factor to CC in our population. A
      case-controls study was performed. DNA was obtained from paraffin-embedded
      cervical fixed tissue samples. Analysis of the p53 genotype at position 72 was
      performed by polymerase chain reaction using specific primers and Accll
      digestion. Among cases with CC the proportions of the p53 genotypes at codon 72
      were 0.05 to proline homozygous, 0.5 to heterozygous, and 0.45 to arginine
      homozygous. In controls the proportions were 0.08, 0.62, and 0.31. X2 test showed
      no significant difference In the proportions. We conclude than In our population,
      as other worldwide countries, the homozygous for arginine at codon 72 of the p53
      gene is not a risk factor to cervical cancer.

PMID- 12221911
TI  - [1st revision of the National Consensus on Breast Cancer Treatment].

PMID- 12221912
TI  - Aging and rule learning: the case of the multiplicative law.
AB  - This work examined the effect of age on the ability to learn multiplicative
      combination rules. Participants learned the multiplicative relationship between
      daily tobacco intake, daily alcohol intake, and risk of esophageal cancer. The
      hypothesis was that younger adults would learn to implement a multiplicative
      combination rule and older adults would not, despite feedback. Among the younger
      adults, complete rule learning took place. Before receiving feedback, they used
      an underadditive rule, a result consistent with previous studies. After only a
      limited amount of feedback, they learned to use a multiplicative rule. Even after
      receiving feedback, however, the older adults still showed difficulties in using
      the multiplicative rule. These results strengthen the proposition by Chasseigne,
      Mullet, and Stewart (1997) that the differences between younger and older adults
      in function learning are related mainly to flexibility of functioning.

PMID- 12221913
TI  - Aging and effect of predictability on reality monitoring.
AB  - This study compared the direction of source confusions and the effect of
      predictability on reality monitoring for internally generated information and
      externally derived information in younger (mean age 19-25) and older (mean age 70
      85) adults. Participants were invited to listen to the conclusions of simple
      stories or to generate and imagine them. Conclusions could be either highly
      predictable (Experiment 1) or unpredictable (Experiment 2). The change in
      predictability produced changes in the direction of source confusions only in
      older adults. When a story ended in a predictable way, older adults attributed to
      imagination conclusions that were actually perceived, whereas the pattern of
      confusions tended to reverse with unpredictable stories.

PMID- 12221914
TI  - Mathematics of forgiveness.
AB  - This study was aimed at determining the integration rule--summation or averaging-
      underlying the forgiveness schema. The main reason for distinguishing between
      these structures is that they have very different practical implications
      regarding the influence of various factors specific to each case on the
      propensity to forgive. In a summative model, the impact of the different factors
      and the direction of the effects are constant. For example, the presence of
      apologies always is a positive element even when these apologies assume a very
      weak form. By contrast, in an averaging model, the apologies can be a positive or
      a negative element depending on the current level of propensity to forgive and
      the form of the apologies. Two experiments were conducted using the functional
      theory of cognition framework. Experiment 1 applied the missing information test.
      Experiment 2 applied the credibility of information test. In both experiments,
      clear evidence favored a summative rule for judging willingness to forgive from
      circumstantial information such as presence or absence of intent, presence of
      absence of apologies, and degree of cancellation of consequences.

PMID- 12221915
TI  - Free recall accuracy for common and bizarre verbal information.
AB  - A large body of empirical research suggests better free recall for bizarre than
      common verbal information; however, the bulk of those studies used a method that
      does not consider the contextual and relational accuracy of recovered memories.
      The conclusions drawn from that research therefore are based on tests of memory
      not for holistic stimuli but for decontextualized memory fragments. In response
      to this anomaly and recent findings suggesting that bizarre memories are more
      likely to be distorted than common memories, a holistic analysis of free recall
      for common and bizarre verbal material was conducted. Two experiments indicated
      that bizarreness both facilitates and disrupts recall. Specifically, better
      recall (both in part and in full) was found for bizarre information, but a
      greater tendency to merge bizarre memory fragments into other partially recovered
      memories was also found. This pattern of results was demonstrated under immediate
      and delayed testing conditions (Experiment 1) and using both incidental and
      intentional learning procedures (Experiment 2). Overall, the results are
      consistent with a weak account of disruption caused by bizarreness.

PMID- 12221916
TI  - The relative influence of attitudes and subjective norms from childhood to
      adolescence: between-participant and within-participant analyses.
AB  - Children and adolescents (ages 8-16) were asked to indicate their behavioral
      intentions, attitudes, and subjective norms for 34 behaviors. Between-participant
      and within-participant analyses demonstrated that attitudes and subjective norms
      were good predictors of behavioral intentions both singly and in combination. In
      addition, attitudes generally were better predictors than were subjective norms
      both across behaviors and across participants. Most importantly, however, there
      were no differences in the relative importance of attitudes and subjective norms
      in predicting behavioral intentions across age groups.

PMID- 12221917
TI  - The generativist-interactionist debate over specific language impairment:
      psycholinguistics at a crossroads.
AB  - Certain defining problems in psychology force us to clarify both the origins and
      the limits of a paradigm that has long governed our thinking in a particular area
      of research. The current debate over the nature and causes of specific language
      impairment is proving to be just such an issue. In particular, the existence of
      the KE family, 15 of whose 37 members suffer from specific language impairment,
      has raised far-reaching questions about the conceptual foundations of our current
      views about language deficits and, indeed, about language development in general.

PMID- 12221918
TI  - Working together to hit the 'moving target' of health care safety.

PMID- 12221919
TI  - Delays in treatment.

PMID- 12221920
TI  - Statistics provide insight into causes of sentinel events.

PMID- 12221921
TI  - Committing to surveyor excellence through certification exam.

PMID- 12221922
TI  - Improving your organ donation program.

PMID- 12221923
TI  - Effect of the intestinal flora on amyloid deposition in a transgenic mouse model
      of familial amyloidotic polyneuropathy.
AB  - Familial amyloidotic polyneuropathy (FAP) is a hereditary disease characterized
      by the systemic accumulation of amyloid fibrils. A mutant transthyretin (TTR)
      gene is mainly responsible for the disease. However, the variable age of onset
      and low penetrance might be due to environmental factors, one of which is the
      intestinal flora. Three types of intestinal flora were introduced into a
      transgenic (Tg) mouse FAP model, 6.0-hMet30. The CV1 and CV2 group transgenic
      mice were transferred with the intestinal flora from two different mouse
      facilities housed under conventional conditions, and the SPF group transgenic
      mice were kept under specific pathogen free conditions in our facility. All the
      mice were maintained under controlled temperature, humidity and bacterial
      conditions. Over a period of 28 months, amyloid was not deposited in the SPF and
      CV1 groups. In contrast, amyloid was deposited in the esophagus and small
      intestine of two of the three CV2 mice at 18 months. Many neutrophils infiltrated
      the lesions. The numbers of tissue neutrophils were higher in the CV2 group than
      in the SPF and CV1 groups at 18 months. The CV2 flora included fewer gram
      positive anaerobic cocci as well as higher proportions of yeasts, staphylococci
      and enterobacteriaceae compared with the SPF and CV1 flora. These findings
      suggest that the intestinal flora plays an important role in amyloid deposition.

PMID- 12221924
TI  - Development of a diet for long-term raising of F344 rats--relationship between
      dietary digestible crude protein content and digestible energy content.
AB  - Mice and rats are frequently subjected to long-term raising in studies of aging.
      These animals are usually given growing or breeding diets from a young age. This
      raising method causes diseases such as chronic nephropathy with proteinuria due
      to nutritional excess. Consequently, a long-term raising study on male F344/DuCrj
      rats using nine sorts of diets differing in crude protein (CP; 12, 28, 44%) and
      digestible energy (DE; 2.8, 3.7, 4.5 kcal/g) contents was carried out. It was
      found that feed consumption was regulated by DE, not digestible crude protein
      (DCP) intake. Body weight was controlled within low energy areas, and was not
      influenced by feed or DCP intake. The liver and kidney weight at 105 weeks of age
      increased in response to an increase in the level of CP in the diet. Chronic
      nephropathy was severe in rats fed high protein diets and moderate levels of
      protein with moderate to high energy diets. Fatty liver and bile duct hyperplasia
      were found in rats fed a high protein and high energy diet. Few pathological
      findings of kidney and liver were found in the low protein and low energy diet
      group. The reduction of disorders attributable to excess energy or inappropriate
      diet suggests that low protein and low energy diets are most suitable for long
      term raising in this strain of rat.

PMID- 12221925
TI  - Electron-beam sterilization of laboratory animal diets--sterilizing effect of 10
      MeV electrons from a linear accelerator.
AB  - Electron beam sterilization for laboratory animal diets was examined as an
      alternative to 60Co gamma rays. Solid, powder diets for "mice and rats" and solid
      diets for "rabbits and guinea pigs" which are the main products sterilized by
      60Co gamma rays were irradiated with 10-MeV electrons from a linear accelerator
      at the Research Institute for Advanced Science and Technology, Osaka Prefecture
      University. At least 20 kGy was required to sterilize the samples irrespective of
      solid or powder diets, which was in good accordance with the results for 60Co
      gamma rays. Using a set dose of 30 kGy, a thickness of 45 mm for solid diets and
      30 mm for powder diets could be sterilized by "one-sided" irradiation. "Dual
      sided" irradiation could sterilize all the solid diets and the powder diets
      contained in the thicknesses of 90 mm and 75 mm, respectively. Irradiation
      effects of 10-MeV electrons on the nutrient quality of each diet were almost
      equivalent to those of 60Co gamma rays. These results suggest that commercially
      adopted sterilization doses for 60Co gamma rays are applicable to electron
      sterilization without modification if the depth-dose profile and the minimum dose
      of irradiated samples are precisely assessed.

PMID- 12221927
TI  - Breeding of African green monkeys (Cercopithecus aethiops) under indoor
      individually-caged conditions.
AB  - This paper reports the results of reproduction with 45 wild African green monkeys
      (Cercopithecus aethiops) (36 females and 9 males) during the nine years from 1981
      to 1989 under indoor individually-caged conditions. In 206 cases of menstruation
      observed, menstrual discharge lasted for 2.5 +/- 1.2 days in cycles of 22-48
      days, and the length of each menstrual cycle was 31.2 +/- 6.5 days. Females who
      had regular menstrual cycles were subjected to "one-to-one timed mating"; females
      and males were put together on a one-to-one basis daily only for a certain period
      of time on and after the day of ovulation. Females who had irregular menstrual
      cycles or had no menstruation were subjected to "every-other-day mating"; females
      and males were put together on a one-to-one basis every other day for at least 16
      weeks. The pregnancy rate (No. of pregnant females/No. of mated females) by one
      to-one timed mating was 48.9% (116/237); 2.0 mating trials were needed to obtain
      one case of pregnancy. On the other hand, the pregnancy rate (No. of pregnant
      females/No. of mating trials) by every-other-day mating was 96% (48/50). Females
      who delivered normally totaled 129. The mean gestation period was 165 days when
      males, weighing 343 g on average at birth, were delivered, and 166 days when
      females, weighing 318 g on average at birth, were delivered. The male and female
      newborns were nursed for 131 and 138 days, respectively, on average. Details are
      summarized in Table 3. This paper also reports 23 cases of abortion, 6
      stillbirths, and 6 cases of Caesarean section, by which three live fetuses and
      three dead fetuses were obtained.

PMID- 12221926
TI  - Pretreatment of leishmania homologue of receptors for activated C kinase (LACK)
      promotes disease progression caused by Leishmania amazonensis.
AB  - A cDNA coding Leishmania homologue of receptors for activated C kinase (LACK),
      which was known to play an important role in the early phase of Leishmania
      infection, was molecularly cloned from Leishmania amazonensis promastigote by
      using reverse transcription and nested polymerase chain reaction, and was
      sequenced. The L. amazonenis LACK cDNA showed 97.3 to 99.3% homology and its
      deduced amino acid sequence showed 98.7 to 99.7% identity in comparison with LACK
      sequences from five other species. The amino acid sequences in the immunodominant
      peptide region were completely conserved among Leishmania spp. tested.
      Intravenous pretreatment of the recombinant L. amazonensis LACK into BALB/c mice
      showed progressive lesion development compared to PBS (-) injected control mice,
      suggesting the important role of LACK in the early phase of L. amazonensis
      infection.

PMID- 12221928
TI  - The daily pattern of cardiovascular parameters in Kurosawa and Kusanagi
      Hypercholesterolemic (KHC) rabbits.
AB  - We studied characteristics of the daily pattern of heart rate (HR), blood
      pressure (BP), body temperature (BT), and locomotor activity (LA) in conscious
      and unrestrained Kurosawa and Kusanagi-Hypercholesterolemic (KHC) rabbits and age
      matched normal Japanese white (JW) rabbits, using a telemetry system. In all JW
      rabbits, nocturnal patterns were observed in HR, BT and LA. In the 5 months group
      of KHC rabbits, however, diurnal rhythm was observed in HR, and in the 10 months
      group of KHC rabbits, it was also shown in LA. The nocturnal pattern was observed
      only in BT in 10 months KHC rabbits. Mean blood pressure (MBP) in JW and KHC
      rabbits showed no clear daily pattern. The mean daily values of HR and BT were
      not altered between the 5 months and 10 months groups in KHC rabbits, although
      those in JW were lower in the 10 months group than in the 5 months group.
      Moreover, the daily values of HR and MBP in KHC rabbits tended to be higher than
      those in the age-matched JW rabbits. The pulse pressure in the 10 months group of
      KHC rabbits tended to be greater than the 5 months groups of KHC and JW rabbits.
      Furthermore, short-term variabilities in BP in the 5 months KHC rabbits were
      significantly lower than those in the other groups. From these results, it is
      suggested that the cardiovascular function, including the autonomic nervous
      function is altered with the development of atherosclerosis in KHC rabbits.

PMID- 12221929
TI  - Transplacental transport of alpha 2-macroglobulin (alpha 2M) and induction of
      alpha 2M in maternal and neonatal rats with acute inflammation.
AB  - The aims of this study were to investigate transplacental transport of alpha 2
      macroglobulin (alpha 2M) in rats in rats and to examine the degree of alpha 2M
      induction in maternal and neonatal rats with acute inflammation. Serum was
      collected from healthy pregnant CD (IGS) rats, neonates of the pregnant rats and
      their cord blood. Additional serum samples were obtained from pregnant rats
      inoculated with an inflammatory agent, turpentine oil, their neonates and cord
      blood, and neonates inoculated with turpentine oil. The serum levels of alpha 2M
      were measured by means of an enzyme-linked immunosorbent assay. The average serum
      levels of alpha 2M in healthy neonates and cord blood were about 380
      micrograms/ml. Serum a2M level in neonates inoculated with turpentine oil
      averaged about 580 micrograms/ml. Serum alpha 2M levels in maternal rats
      inoculated with turpentine oil, neonates from those rats and their cord blood
      were elevated, the values being 2,000 micrograms/ml or higher. It was
      demonstrated that induction of alpha 2M in neonatal rats was lower than in
      maternal rats when inoculated with turpentine oil. These results suggest that
      alpha 2M is transplacentally transported from maternal rats to fetal ones.

PMID- 12221930
TI  - Experimental eradication of pinworms (Syphacia obvelata and Aspiculuris
      tetraptera) from mice colonies using ivermectin.
AB  - A spray administration of ivermectin was evaluated for the treatment of pinworm
      infection in mice. In this study, a spray of 0.1% ivermectin injectable solution
      over the entire cage once a week, for three consecutive weeks (one cycle
      treatment), was effective in eradicating both Syphacia obvelata and Aspiculuris
      tetraptera from mice under experimental conditions. In addition, no acute
      toxicity was observed in 105 mothers or 687 neonates treated with ivermectin,
      indicating that ivermectin does not affect murine reproduction. Finally, we
      attempted to eradicate pinworms from infected mice in our institute using this
      method. Two cycles of treatment were administered, with a two-week pause between
      cycles, resulting in complete eradication for at least one year. Treating mouse
      colonies with spray ivermectin is inexpensive, safe, requires very little labor
      and is very effective at eradicating pinworms from mice.

PMID- 12221932
TI  - Cryopreservation of brain tissue for primary culture.
AB  - Factors affecting recovery of brain cells from cryopreserved cerebral tissues of
      fetal rats were examined based on yields of viable cells on cell culture.
      Favorable preservation was obtained with freezing small pieces (less than 1 mm
      cube) of brain tissues rather than whole tissues or dissociated single cells, and
      use of 10% dimethylsulfoxide as a cryoprotectant in liquid nitrogen. As for cell
      preparation procedures, cell survival was improved when tissues were heated at 32
      degrees C during papain digestion and centrifugation. Under favorable conditions,
      the number of brain cells recovered from cryopreserved tissues corresponded to 20
      30% of those from fresh control tissues. Immunocytochemical characteristics of
      cultured neurons, astrocytes, and oligodendrocytes from cryopreserved and fresh
      tissues were indistinguishable. Semi-quantitive analyses of microtubule
      associated protein-2 (MAP-2) and synaptophysin revealed that there was no
      difference in the amounts of these markers between cultures from both fresh and
      cryopreserved tissues. These results suggest that most of all cell types
      including neurons were equally susceptible to the cryopreservation procedures. We
      concluded that cryopreservation in liquid nitrogen is an effective method for
      preservation of embryonic brain tissues for later use in cell culture studies.

PMID- 12221931
TI  - Direct production of gene-targeted mice from ES cells by nuclear transfer and
      gene transmission to their progeny.
AB  - In order to evaluate the usefulness of a cloning technique to produce gene
      manipulated mice for the field of laboratory animal science, we produced mice
      cloned from gene-targeted embryonic stem (ES) cells and examined the vertical
      transmission of a targeted gene to their progeny. Of 1257 eggs constructed by
      nuclear transfer using M-phase ES donor cells targeted with an oviduct-specific
      glycoprotein (OGP) gene, 990 formed a pseudo-pronucleus and a polar body after
      activation. Of 504 cloned embryos transferred into recipients, 20 live cloned
      pups (2%) were recovered by Caesarean section at 19.5 days of gestation. Fourteen
      of these cloned mice were studied. Genotyping of the OGP locus and 20
      microsatellite loci showed that they were genetically identical to the OGP gene
      targeted TT2 cells. Eight cloned pups grew into adults, of which 7 were male and
      1 was female (missing the Y chromosome). Mating experiments using the cloned mice
      were carried out. Of 89 F1 mice produced from the mating of cloned and C57BL/6J
      mice, 50 had the targeted OGP gene heterozygously. Thirty-seven F2 mice from 4
      pairs of the OGP-/+ mice were composed of 9 OGP-/-, 18 OGP-/+, and 10 OGP+/+.
      Moreover, 26 offspring of one pair of the cloned mice were composed of 10 OGP-/-,
      12 OGP-/+, and 4 OGP+/+. These offspring were fertile and transmitted the mutant
      OGP gene to the next generation. Comparison of these results with those of
      germline chimeric mice indicates that gene-targeted mice can be produced at least
      one generation earlier by nuclear transfer than by the conventional methods. In
      addition, the targeted OGP gene was constantly transmitted to the progeny of the
      gene-targeted mice. Cloning techniques are potentially a more efficient way to
      generate gene-manipulated mice for laboratory animal science, although such
      techniques include many unresolved problems, such as low production efficiency,
      and selection of a cell source for gene manipulation among others.

PMID- 12221933
TI  - Genotyping the mouse severe combined immunodeficiency mutation using the
      polymerase chain reaction with confronting two-pair primers (PCR-CTPP).
AB  - An allele specific polymerase chain reaction with confronting two-pair primers
      (PCR-CTPP) was developed as an assay for genotyping the mouse Prkdcscid gene
      mutation (former name scid). The reverse primer (WR) was designed to include the
      antisense nucleotide (A) specific for the wild type allele at the 3' end with the
      counterpart forward primer (F) upstream. The other forward primer (MF) was
      designed to include the sense nucleotide (A) specific for the Prkdcscid mutation
      at the 3' end with the other counterpart reverse primer (R) downstream. PCR was
      performed in a single tube with these two pairs of primers. The products specific
      for each allele extended by F/WR (101 bp) or MF/R (180 bp) were visualized with
      common PCR products (257 bp) extended by F/R, and three genotypes of mice
      (Prkdcscid/Prkdcscid, Prkdcscid/+, and +/+) were clearly distinguished.

PMID- 12221934
TI  - Novel development of mammary glands in the nursing transgenic mouse ubiquitously
      expressing WAP gene.
AB  - Although whey acidic protein (WAP) has been suggested to have some biological
      functions, its true function has not yet been clearly elucidated. We have
      generated transgenic mice ubiquitously and highly expressing the WAP gene. The
      pups born from one female among these transgenic mice showed low growth or died
      during nursing. This transgenic founder showed novel development of the mammary
      glands, and demonstrated normal parturition and nursing behavior. The mammary
      glands showed low-distended ductal structures, and poor development of lobulo
      alveolar and acinous formations despite normal nursing, while mammary ducts were
      rather large in comparison with those of normal lactating females. Although this
      founder was found to be mosaic for transgenesis, it was shown to be a useful
      animal model for investigating WAP function.

PMID- 12221935
TI  - Elimination of Pasteurella pneumotropica from a contaminated mouse colony by oral
      administration of Enrofloxacin.
AB  - Enrofloxacin, a fluoroquinolone bactericidal antibiotic, was administered in an
      attempt to eradicate Pasteurella pneumotropica (P. pneumotropica) from a
      contaminated mouse colony. Contaminated mice, maintained within 4 animal rooms,
      were administered Enrofloxacin in drinking water at a daily dosage of 25.5 mg/kg
      for 2 weeks. Following one week of Enrofloxacin treatment, mice were selected
      randomly from each room and examined for P. pneumotropica. This procedure was
      repeated two or three times until all mice examined tested negative for the
      Pasteurella strain. With the exception of one room, treated mice consistently
      tested negative for P. pneumotropica for up to 45 weeks following completion of
      Enrofloxacin treatment. Thus, oral administration of Enrofloxacin significantly
      eliminated P. pneumotropica from a contaminated mouse colony.

PMID- 12221936
TI  - Activation of latent pseudorabies virus infection in mice treated with
      acetylcholine.
AB  - Pseudorabies virus (PrV) YS-81 strain latently infected in 6-week-old BALB/c mice
      was detectable by nasal swabbing, and serum antibody was shown to increase in
      titer after intraperitoneal injection for 3 days with acetylcholine or
      dexamethasone.

PMID- 12221938
TI  - [Analysis of the practical use of terms attributed to nursing phenomena in the
      ICNP (International Classification for Nursing Practice)--alpha version].
AB  - This study had the purpose of analysing the utilization of terms attributed to
      nursing phenomena in the practice of nurses from the state of Paraiba, Brazil.
      The results showed that all terms are used by nurses in some frequency. In
      respect to the utilization of the terms, according to a stratified sample, the
      results showed that nurses from other municipal districts use a higher number of
      terms, statistically significant, when compared with data from the cities of Joao
      Pessoa and Campina Grande. From the results of the study, it can be concluded
      that terms attributed to phenomena contained in the CIPE--Alpha Version represent
      problems or situations in the nursing practice of nurses from Paraiba,
      corroborating the affirmation of the International Council of Nurses that these
      terms are common to nurses all over the world.

PMID- 12221937
TI  - Histological study on intestinal diverticulum of tree shrew (Tupaia javanica).
AB  - Tree shrews possess an intestinal diverticulum. We investigated this diverticulum
      with histological and immunohistochemical methods to determine whether this
      diverticulum was cecum or not. The ratio of the length of diverticulum/small
      intestine was apparently shorter than that of several primates. In the
      histological study, mucous membrane of the small intestine was shifted to that of
      the large intestine at the junction of the diverticulum. Histological features of
      the diverticulum were similar to those of the large intestine, but the shape of
      mucousal surface was rather simpler than that of the large intestine.
      Immunohistochemical study revealed 5-HT positive cells in the bottom of crypts
      and CD3- and CD 8-positive lymphocytes in lymphoid nodules. These findings
      suggest that the tree shrew has a cecum with primitive characteristics.

PMID- 12221940
TI  - [Dominance and resistance in nursing work].
AB  - This study aims to investigate the forms of domination which are present in the
      daily work of hospital nurses and the way they handle these occurrences, as well
      as the types of mediating processes which occur within relationship which produce
      confrontation and the way these help them to comprehend and transform their own
      work.. A qualitative methodology was used which included indepth interviews with
      15 nurses, as well as analysis of official documents from both the Regional
      Council of Nurses and the Nurses' Union from the state of Ceara. The study
      concluded that forms of domination not only exist but also contribute to the
      reproduction of unequal relationships on the job, and that these relationships
      occur between nurses and doctors, between peers and between nurses and auxillary
      personnel. Responding to this situation, nurses have been utilizing individual
      and informal resistance mechanisms and strategies, but also formal and collective
      resistance strategies have been used, these latter less frequently.

PMID- 12221939
TI  - [Concepts and scenarios in the teaching of psychiatric nursing and mental
      health].
AB  - This work approaches the contradictions that are present in the teaching of
      Psychiatric Nursing and Mental Health in four public universities in the state of
      Rio Grande do Sul, Brazil. It consists of a qualitative study based on a
      dialectic referential. The instruments used for the investigation were the
      programs of the courses of Psychiatric Nursing and Mental Health and interviews
      with fifteen teachers and fourteen students of the area. The central themes of
      the analysis were the conceptions and scenarios in which the teaching of
      Psychiatric Nursing and Mental Health takes place. It was observed that these
      courses focus predominantly the concepts of normality and pathology during the
      cycle of life and are influenced by the discourse of preventive psychiatry and by
      psychoanalysis. It was also noticed that the courses mentioned adopt a
      psychodynamic approach. The majority of the training in the area still takes
      place in big psychiatric hospitals and emphasizes psychopathologies and its
      psychosocial determinations which consolidate the hospice model.

PMID- 12221941
TI  - [Nursing: the integrated curriculum in the evaluation and perception of the
      nursing faculty].
AB  - The following study aims at determining the perspectives and difficulties
      experienced by the teaching staff of the Nursing Department at the Health
      Sciences Center in Londrina State University during the development and
      implementation of Module I of their integrated curriculum. The research was
      constituted by a case study and data were obtained from a set of questions posed
      to 13 (thirteen) teachers who designed and implemented the Module I of the
      integrated curriculum at the nursing school in Londrina State University, during
      the year of 2000. The analysis of the data allowed the authors to determine those
      factors which either made it difficult or facilitated the process implementation,
      as well as to raise teachers' perception about the process of curricular change.
      The study, by supplying indicatives of change, contributes to the improvement of
      the quality of nursing education as the new curriculum is implemented at Londrina
      State University.

PMID- 12221942
TI  - [Epidemiological profile of elderly HIV/AIDS patients].
AB  - The present study is the result of an experience in the hospital Correia Picanco
      in Recife, Pernambuco Federal State, a reference hospital for HIV patients. The
      objective of this investigation is to supply the discrepancy of information on
      elderly carriers of HIV. This is a quantitative, transversal and retrospective
      research. A diagram form was used to organize the data collected from 46 medical
      records. Results showed that there was an increase on the number of women,
      especially married women, heterosexuals, and elderly infected by HIV. The study
      also showed an increase on the number of infections through sexual contact and
      the predominance of carriers who were undereducated. It was also observed that
      the medical records were incomplete. The conclusion was that preventive education
      programs have to be elaborated in order to reach the population in general,
      including the elderly.

PMID- 12221943
TI  - [Representation about health production in the family circle of patients with
      tuberculosis].
AB  - The study investigates the labor process in health production, with the purpose
      of knowing what representation tuberculosis patients make of health production
      within the family group and its potential for determination of the disease. It is
      understood that this social group contains, in its interior, potential to provoke
      and to determine the production process and the reproduction of
      congruity/incongruity in social individuals.

PMID- 12221944
TI  - [Occupational risk of acquiring tuberculosis among hospital nursing personnel].
AB  - At hospitals, patients with tuberculosis are attended by several professionals
      and among them nursing workers. These workers are subjected to the risk of the
      tuberculosis infection. This study had the objective of investigating the number
      of nursing workers in a hospital that acquired tuberculosis in a pre-determined
      period and their general characteristics; to calculate the morbidity coefficient
      of this disease and discuss the occupational risk among these workers. In one
      year, health workers presented 3.86 times greater risk, and, in another year,
      1.47 times greater risk. In the present study tuberculosis was considered an
      occupational hazard for hospital nursing workers.

PMID- 12221945
TI  - [Institutionalization and development of nursing in Brazil in view of public
      health policies].
AB  - The paper deals with a historical recovery of the genesis of Nursing and its
      development in Brazil in order to elucidate its influence in current nursing
      education and practice. It emphasizes the role played by the Rockefeller
      Foundation in the organization of public health nursing, the creation of the
      first school of nursing and the consolidation of nursing education and practice
      in hospitals. Certain public health policies were also examined, given their
      influence in the development of the profession. Nursing maintained a scientific
      and politically neutral position during the implementation of these health
      policies, possibly because of the non-critical makeup brought about by the
      adoption of the flexnerian model of teaching, in its link to Medicine.

PMID- 12221946
TI  - [Hospital nursing service--introducing this silent giant].
AB  - This article shows the importance of the nursing service in the health
      organizations. The metaphor "giant" will be used to describe the extent of this
      service, and the term "silent" will be used to refer to the little acknowledgment
      the nursing service receives from the community. The extent and complexity of the
      nursing assistance is vital for the effectiveness of the processes of health
      care, however its structure and organization is unknown by the community. The
      nursing service congregates a great number of personnel with different levels of
      education. The planning, organization, structure and operation of this service
      follow the principles of the General Theory of Administration. Knowledge from
      this area has also been used to help health institutions to achieve its goals and
      objectives. This study also approaches the client and the quality of health
      assistance, pointing out the need of reexamining the administrative model adopted
      and looking forward to systemic alternatives.

PMID- 12221947
TI  - [The job of the manager of a basic health care unit: practice possibilities].
AB  - This article deals with the management of basic health care units, which in the
      context of municipalization of health, is being placed as strategic to the
      consolidation of the health care model prescribed by the Integrated Health Care
      System. It intends to contribute to the process of reflection concerning
      management, pointing out some possibilities for the manager's work in its
      administrative, technical and political dimensions.

PMID- 12221948
TI  - [Theoretical study of the demarcation of the intestinal stoma].
AB  - The present research focuses on the study of intestinal stoma demarcation. It
      reviews the historical development of the knowledge produced in this field,
      considering the advancement implemented in the area of abdominal surgeries which
      proposes the externalization of intestinal segments. In order to make the
      demarcation of intestinal stoma, it is necessary to limit the ideal region and to
      perform it with special pen which will propitiate the making of an anatomically
      appropriate opening. The stoma should favor the adaptation of devices which do
      the collection of effluents from the patient's intestines with a minimum of
      discomfort to the patient. The choice for the localization of the stoma, which is
      based on scientific principles, is made taking into consideration the structure
      of the recto-abdominal muscle and the distance from critical areas. At last, the
      most performed techniques of demarcation of the intestinal stoma are presented,
      as well as the procedures to be followed by the nurse or by the stoma therapist
      nurse.

PMID- 12221949
TI  - Chronic obstructive pulmonary disease: a ten-year review of clinical features in
      O.A.U.T.H.C., Ile-Ife.
AB  - The case notes of all patients admitted for chronic obstructive pulmonary disease
      (COPD) between 1990-1999 were reviewed. A total of 160 cases satisfied the
      American Thoracic Society criteria for COPD and were subsequently analyzed. The
      age of the patients ranged from 41-90 years: with a mean of 65 years. The male
      female ratio was 4:1. Indoor pollution and smoking were found to be the commonest
      aetiological factors; while farming and trading were the major occupational
      groups at risk. The clinical features of the patients showed a mixed pattern of
      chronic bronchitis and emphysema. The study identifies the need to make an early
      diagnosis and commence appropriate treatment to retard progression to severe
      disease and death.

PMID- 12221950
TI  - Female genital mutilation and reproductive outcome.
AB  - One hundred and thirty cases of obstructed labour were managed amongst 1,860
      deliveries over a period of 2 years. 34 cases were due to acquired gynaetraesia
      following female genital mutilation in infancy and childhood. This paper
      highlights the magnitude, prevalence of this negative traditional practice and
      the effect on reproduction. Measures to reducing this preventable cause of
      maternal mortality are suggested.

PMID- 12221951
TI  - Prevalence and causes of blindness and low vision in Dambatta local government
      area, Kano State, Nigeria.
AB  - In 1995 a population based cross sectional blindness prevalence survey was
      conducted in Dambatta local government area (LGA). 3596 people were examined. The
      prevalence of blindness was 1.14% with 95% confidence limit of (0.8-1.48%). The
      causes of blindness are cataract 54%, Trachoma 17%, Glaucoma 15%, Corneal opacity
      7%, other blinding conditions 7%. The prevalence of low vision was 2.05% with 95%
      confidence limit (1.60-2.50%). One percent of the population were severely
      visually impaired (WHO category 2). The causes of low vision are cataract 55%,
      corneal opacity 14%, uncorrected aphakia 11%, Glaucoma 7%, Refractive error 5%,
      other conditions 8 percent. Cataract was the leading cause of uniocular blindness
      with 53%, others were phthisis bulbi 17%, Trauma 14%, corneal opacity 10%, and
      others 7 percent. Cataract was the single most important cause of blindness, low
      vision and uniocular blindness accounting for 54%, 55%, and 53%, respectively.
      Uncorrected aphakia accounted for 11% of the low vision group, 80% of these had
      couching. This study showed that 93% of the blindness was avoidable in the sense
      that it could have been primarily prevented or, is treatable. 92% of the causes
      of low vision are avoidable.

PMID- 12221953
TI  - Indications for amputations in Ile-Ife, Nigeria.
AB  - This is a retrospective study of limb amputations in Ile-Ife, Nigeria during a
      thirteen-year period (1987-1999). 82 patients were studied with a mean age of 35
      +/- 22 years. 63 of the patients were adults, while 19 patients were children
      aged 15 years and below. Trauma was indicated as a reason for amputation in 60
      patients (73.4%). Road traffic accident with peripheral vascular compromise was
      the single most common reason for amputation (41.7%). Forty-seven of the 82
      patients had lower limb amputations, while the others were in the upper limbs.
      There was delay in performing amputation in some patients due to refusal to
      accept the procedure in 10(12.1%), logistics in 5(6.1%) and lack of finance in 3
      (3.7%). The average healing time of the amputation stump wounds was 47 +/- 36
      days. In 68.3% of cases, there was wound infection and the wound healing time was
      63 +/- 45 days, much longer than than the general average. Other complications
      were flap necrosis, gas gangrene, osteomyelitis of the bony stump, and tetanus.
      Six patients died from sepsis and one from chronic renal failure, a hospital
      mortality rate of 8.5%. Prosthesis could not be fitted in any of the patients
      during the hospital admission and only three of the diabetic patients attended
      follow up clinic for up to two years; others absconded within 3 months of
      discharge from hospital. It will be possible to reduce the rate of amputation and
      improve the quality of life of patients with amputation if more attention is
      placed on accident prevention and injury control.

PMID- 12221952
TI  - Socio-demographic and forensic characteristics of alcohol abusers in Jos,
      Nigeria.
AB  - The socio-demographic and forensic characteristics of fifty(50) alcohol abusers
      were examined in a community survey carried out in Kugiya (a predominantly
      Christian Berom ethnic group in Jos) who brew and take predominantly a local
      alcohol, Burukutu. A stratified sampling method was used to select 142 subjects
      who took part in the study, out of whom 50 (54%) males and 23 (46%) females of
      ages 16-54 years were identified as Alcohol Abusers through the use of a 4-item
      CAGE instrument and also the quantity taken. The questionnaire also highlighted
      the socio-forensic characteristics of the studied group. Alcohol abuse disrupts
      social, occupational, interpersonal and marital life and tends to induce criminal
      behaviour.

PMID- 12221954
TI  - Respiratory symptoms and peak expiratory flow rates in workers of a Nigerian soap
      and detergent industry.
AB  - This comparative cross-sectional study was carried out to assess the respiratory
      symptoms and peak expiratory flow rates of the factory(study group) and
      office(control group) workers in a soap and detergent industry in Ilorin in
      relation to the occupational hazards of chemical fumes and detergent dust in the
      industry. Upper respiratory tract infections were found in 67.5% and 10.6% of the
      study group and control group respectively. The study shows that the factory
      workers experienced hazards (e.g. chemical fumes and detergent dust) at work more
      than the office workers. Personal protective devices such as boots, face masks,
      gloves, earmuffs and goggles were not consistently used since they were
      inadequate in supply, worn out and of substandard qualities. The general
      reduction in the mean values of peak expiratory flow rate in the factory workers
      than in the office workers as observed in this study may possibly, be a pointer
      to the effect of industrial exposure to chemical fumes and detergent dust over
      the years. There is the need to follow up these workers in order to detect early
      any possible disease and complications that may arise.

PMID- 12221955
TI  - Medical journals of Nigeria, quo vadis?
AB  - The Nigerian health sector is beset with an underdeveloped Continuing Medical
      Education (CME) programme, a scarcity of reading materials and the lack of a
      reading culture. Recent issues of available journals were obtained and read to
      identify data such as: the ownership and base, presence of mission statement,
      print quality, administrative and editorial matters, abstract format, CME value
      of articles, advertisements, subscription information and communication channels
      and practice. The availability of the journals in the libraries of the three
      'first generation' teaching hospitals and accessibility through the Medline were
      ascertained. Twenty-eight current journals were obtained. Lagos has the highest
      number of editorial bases. Fifteen journals belong to national medical
      associations, 2 to regions and 11 to institutions. The journal title was
      considered appropriate in 13, cover design was good in 15, paper quality was good
      in 20 and legibility was good in 11 journals. Poor editing was manifested by bad
      grammar, spelling and punctuation. Six journals contained review articles of good
      CME value. Eight journals had a full compliment of communication facilities. The
      existence of a functional independent administrative office or staff was
      indicated in 7 journals. No journal indicated the dates of submission and
      acceptance of articles. Twenty-one journals were on the shelf of the library of
      ABUTH, Zaria. Two journals are accessible through the Medline and another is on
      line. Adequate funding and improved management will effectively address most of
      the problems identified.

PMID- 12221956
TI  - Prosthetic treatment of oligodontia with a tooth-supported overdenture--a case
      report.
AB  - An unusual case of oligodontia is reported in a 20 year old Nigerian male. It is
      unusual because of the isolated occurrence of the oligodontia which is
      unassociated with a family history or any other clinical features suggestive of
      specific syndromes or severe systemic abnormality. The patient presented with
      conically or peg shaped anterior and malformed posterior teeth in both the
      maxilla and mandible. Full mouth periapical radiographs revealed stunted roots,
      widening of the periodontal space and an unerupted tooth in the right mandibular
      premolar region. Tooth-supported upper and lower removable partial overdenture
      were fabricated for him. This modality of treatment is a better choice which
      helps not only to preserve the alveolar ridge height and improve aesthetics, but
      also preserves the proprioceptive mechanisms associated with the periodontal
      membrane of natural teeth.

PMID- 12221957
TI  - Appraisal on fluid and electrolyte management in paediatric surgical patient.
AB  - Fluid and electrolyte disorders are common occurrences in Paediatric surgical
      practice. Despite this, the management of fluid and electrolyte imbalance in the
      paediatric surgical patients remains problematic. This is partly because
      authorities vary considerably in their recommendations for therapy, despite the
      great advances being attained in the understanding of the fluid and electrolyte
      homeostasis in the Paediatric age group. This has, in no doubt, resulted in a
      number of morbidity and mortality that could have been prevented based upon
      rational and acceptable recommendations for fluid and electrolyte therapy in
      children. In this review, the normal homeostasis, disorders and management of
      fluid and electrolyte and corrections of metabolic disorders in children are
      highlighted, with the aim to update the practice of fluid and electrolyte therapy
      in children.

PMID- 12221958
TI  - The role of ultrasound in obstetrics.
AB  - Ultrasound contributes immensely to obstetrics and its application and use is now
      widespread. The clinical applications and uses of ultrasound include confirmation
      of pregnancy and multiple gestation, estimation of gestational age, localisation
      of placenta and monitoring of foetal wellbeing. The others are evaluation of
      caesarean section scar integrity and post partum haemorrhage. Ultrasound is also
      useful in prenatal diagnosis and foetal therapy. The major limitation of
      ultrasound is the fact that it is not useful in air/gaseous containing media.
      Ultrasound is safe and there is no known adverse effect for now on mother, foetus
      or operator at the intensity used for present obstetric examination.
      Overdependence and abuse of ultrasound remains a problem and it should be
      emphasised that ultrasound is to complement and not a substitute to clinical
      judgement.

PMID- 12221959
TI  - Acute colonic pseudo-obstruction (Ogilvie's syndrome). A case presentation and
      review of literature.
AB  - The syndrome of acute colonic pseudo-obstruction popularly known as Ogilvie's
      syndrome is an infrequent pathology and has been the subject of numerous medical
      communications in the past two decades. Its aetiology and pathophysiology remains
      poorly understood and patients are still treated inappropriately. In this report,
      a patient with acute colonic pseudo-obstruction managed surgically is presented.
      The pathogenesis and surgical management of this condition is also reviewed.

PMID- 12221960
TI  - Gestational thrombo-embolic disorders.
AB  - Even though it appears that pulmonary embolism might be an infrequent cause of
      maternal mortality in our environment it could be rapidly fatal when it occurs.
      As many as 10% of asymptomatic females with deep venous thrombosis can develop
      pulmonary embolism. Pregnancy being a hypercoagulable state could predispose to
      the disorder in the presence of other factors. Making a categorical diagnosis
      could however be problematic especially in Sub-Saharan Africa where necessary
      facilities might not be available. This present review was undertaken to provide
      an update in diagnosis and management of the disorder in pregnancy with the aim
      of guiding clinical decision-making with respect to diagnosis, management
      modalities, evaluation and preventive measures.

PMID- 12221961
TI  - Conjunctival impression cytology and biochemical assessment of vitamin A status
      in Nigerian children.
AB  - The study was part of a national survey designed as cross-sectional population
      survey to estimate the prevalence of Vitamin A deficiency in Nigeria. A
      multistage cluster random sampling technique was used to select about 163
      children between 6 and 71 months of age in 2 health zones of Nigeria, for
      assessment of their vitamin A status. Conjunctival Impression Cytology (CIC) was
      compared with biochemical method by estimating serum level of vitamin A using the
      reverse phase high pressure liquid chromatography (HPLC). Conjunctival
      impressions were taken from both temporal bulbar conjunctivae of 483 children
      using the disc applicator. CIC showed significant association with low serum
      retinol (0.70 umol/l) levels. Children with abnormal CIC had 2.6 times the risk
      of having low serum retinol levels compared with those with normal CIC (OR = 2.6,
      95% C.I = 1.03-6.67). When CIC was classified as normal and abnormal at cut off
      points of retinol at 0.70 and 0.35 umol/l, the sensitivity of CIC remained low,
      while the specificity remained high. Although our study did not demonstrate
      valuable use of CIC as a screening tool under field conditions in a tropical
      environment like Nigeria, our impression is that, if the technique is further
      refined and evaluated, there is a high potential for its use in developing
      countries, because of its simplicity, practicability and non-invasiveness.

PMID- 12221962
TI  - Twin births at University of Maiduguri Teaching Hospital: incidence, pregnancy
      complications and outcome.
AB  - In a five year retrospective study (between January 1990 and December 1994),
      there were 86 twin births out of 5,953 deliveries at University of Maiduguri
      Teaching Hospital giving a twin delivery incidence of 14.4/1000 birth. Only 82
      case notes were available for this study. Dizygotic twins accounted for 80.5% of
      the cases while monozygotic twins represented 19.5% in the series. Increasing
      maternal age during the reproductive age and positive family history of multiple
      pregnancy were associated with increase twinning rate. The main complications
      encountered during pregnancy were hyperemesis gravidarum, pregnancy-induced
      hypertension and preterm labour. The frequency of preterm labour in this study
      was significantly higher than the observed among the singleton pregnancies within
      the period of study (P < 0.005). The perinatal mortality rate 85.4/1000 births
      was similarly significantly higher than that observed among the singleton
      deliveries (P < 0.005). Compared to singleton pregnancies there was a higher rate
      of caesarean section intervention (P < 0.005). The commonest mode of presentation
      and sex distribution were vertex-vertex and male-female respectively. The vertex
      vertex presentation accounted for 48.8% of all the presentations while the male
      female ratio was 1.2.

PMID- 12221963
TI  - Male contribution to infertility in Ile-Ife, Nigeria.
AB  - This is a retrospective study of 350 cases of male partners of infertile couples
      who presented at the gynaecological and urological units of Ife State Hospital
      branch of Obafemi Awolowo University Teaching Hospital complex Ile-Ife, Nigeria
      within a five year (1993-1997) period. Of the 350 cases reviewed, 200 (57.6%) had
      normal seminal fluid parameters while 27.7% had oligozoospermia and 15.2% had
      azoospermia. The age and past history of sexually transmitted diseases (STDs) had
      significant effect on the result of seminal fluid analysis (p < 0.05
      respectively) while the occupational status had no significant effect (p > 0.05).
      Most of the infertile couple presented with secondary infertility (62%) with a
      significant past history of sexually transmitted diseases (STDs) (p < 0.05).
      Efforts directed to the prevention of STDs should be pursued vigorously by health
      care providers. Education of the populace on responsible sexual habits cannot be
      overemphasized.

PMID- 12221964
TI  - Oral health knowledge, attitude and practices of primary school teachers in Lagos
      State.
AB  - School teachers are known to exert considerable influence on their pupils and to
      an extent on the larger community. They have however been shown to have a
      disappointingly poor knowledge of oral health and disease. This study sought to
      assess the knowledge, attitude and practices of primary school teachers in Lagos
      State, Nigeria. A cross-sectional, questionnaire-based survey was carried out on
      100 primary school teachers drawn from 10 randomly-selected primary schools in
      Lagos State. The results revealed that majority of them have a poor attitude to
      oral health issues. The few of them who have attended a dental clinic mostly had
      extractions done. It was also found that there is a need for improved knowledge
      of oral health disease and their prevention among the teachers for an effective
      school based oral health education programme. The paper suggests ways in which
      this can be achieved.

PMID- 12221965
TI  - Complications from unsafe abortion: presentations at Ilorin, Nigeria.
AB  - This is a retrospective evaluation of the 220 patients that presented at the
      University of Ilorin Teaching Hospital (UITH) with complications from unsafe
      abortions between 1st January, 1986 and 31st December 1999. History of previous
      induced abortion was agreed to by 80.5%, of patients while only 6.8% had previous
      contraceptive use. Sepsis 204(92.7%) with abscess formation in 64.9%, visceral
      injuries 62(28.2%) with haemoperitoneum in 25.9% and maternal mortality was
      recorded in 26.4% of the series. Findings are comparable with previous studies
      from this centre between 1981 and 1985 and with reports from other parts of the
      world. The need for behavioural change by the society and the re-training of
      physicians on post-abortal care is emphasized.

PMID- 12221966
TI  - Congenital malaria in 8 hours old newborn: case report.
AB  - This report, presents a case of congenital malaria in an 8-hour-old female
      neonate. She responded well to oral chloroquine at a dose of 25 mg/kg in divided
      doses over a period of three days and was discharged home for follow-up, 24 hours
      after completion of the course of chloroquine. This case emphasized the need for
      routine screening for malaria in sick newborn infants in malaria endemic regions.
      This is particularly important in situations where clear evidence of sepsis
      cannot be established, either from history or physical examination of the sick
      newborn. Malaria and sepsis have similar clinical features in newborn infants.

PMID- 12221967
TI  - The current classification and diagnostic criteria for diabetes mellitus.

PMID- 12221968
TI  - Paving the path.
AB  - Fortuitous preparation and experiences led to the opportunity to use radioactive
      carbon dioxides to discern the path of carbon in photosynthesis. The search for
      the CO2 acceptor led to recognition of the growth stimulatory effect of methanol
      and its derivatives. With the techniques developed, radiochromatographic
      exploration led to discovery of major membrane lipids containing phosphorus,
      sulfur, and arsenic.

PMID- 12221969
TI  - Revealing the molecular secrets of marine diatoms.
AB  - Diatoms are unicellular photosynthetic eukaryotes that contribute close to one
      quarter of global primary productivity. In spite of their ecological success in
      the world's oceans, very little information is available at the molecular level
      about their biology. Their most well-known characteristic is the ability to
      generate a highly ornamented silica cell wall, which made them very popular study
      organisms for microscopists in the last century. Recent advances, such as the
      development of a range of molecular tools, are now allowing the dissection of
      diatom biology, e.g., for understanding the molecular and cellular basis of
      bioinorganic pattern formation of their cell walls and for elucidating key
      aspects of diatom ecophysiology. Making diatoms accessible to genomics
      technologies will potentiate greatly these efforts and may lead to the use of
      diatoms to construct submicrometer-scale silica structures for the nanotechnology
      industry.

PMID- 12221970
TI  - Abscission, dehiscence, and other cell separation processes.
AB  - Cell separation is a critical process that takes place throughout the life cycle
      of a plant. It enables roots to emerge from germinating seeds, cotyledons, and
      leaves to expand, anthers to dehisce, fruit to ripen, and organs to be shed. The
      focus of this review is to examine how processes such as abscission and
      dehiscence are regulated and the ways new research strategies are helping us to
      understand the mechanisms involved in bringing about a reduction in cell-to-cell
      adhesion. The opportunities for using this information to manipulate cell
      separation for the benefit of agriculture and horticulture are evaluated.

PMID- 12221971
TI  - Phytochelatins and metallothioneins: roles in heavy metal detoxification and
      homeostasis.
AB  - Among the heavy metal-binding ligands in plant cells the phytochelatins (PCs) and
      metallothioneins (MTs) are the best characterized. PCs and MTs are different
      classes of cysteine-rich, heavy metal-binding protein molecules. PCs are
      enzymatically synthesized peptides, whereas MTs are gene-encoded polypeptides.
      Recently, genes encoding the enzyme PC synthase have been identified in plants
      and other species while the completion of the Arabidopsis genome sequence has
      allowed the identification of the entire suite of MT genes in a higher plant.
      Recent advances in understanding the regulation of PC biosynthesis and MT gene
      expression and the possible roles of PCs and MTs in heavy metal detoxification
      and homeostasis are reviewed.

PMID- 12221972
TI  - Vascular tissue differentiation and pattern formation in plants.
AB  - Vascular tissues, xylem and phloem, are differentiated from meristematic cells,
      procambium, and vascular cambium. Auxin and cytokinin have been considered
      essential for vascular tissue differentiation; this is supported by recent
      molecular and genetic analyses. Xylogenesis has long been used as a model for
      study of cell differentiation, and many genes involved in late stages of
      tracheary element formation have been characterized. A number of mutants
      affecting vascular differentiation and pattern formation have been isolated in
      Arabidopsis. Studies of some of these mutants have suggested that vascular tissue
      organization within the bundles and vascular pattern formation at the organ level
      are regulated by positional information.

PMID- 12221973
TI  - Local and long-range signaling pathways regulating plant responses to nitrate.
AB  - Nitrate is the major source of nitrogen (N) for plants growing in aerobic soils.
      However, the NO3- ion is also used by plants as a signal to reprogram plant
      metabolism and to trigger changes in plant architecture. A striking example is
      the way that a root system can react to a localized source of NO3- by activating
      the NO3- uptake system and proliferating lateral roots preferentially within the
      NO3(-)-rich zone. That roots are able to respond autonomously in this fashion
      implies the existence of local signaling pathways that are sensitive to local
      changes in the external NO3- concentration. On the other hand, long-range
      signaling pathways are also needed to modulate these responses according to the
      plant's N status and to coordinate the allocation of resources between the root
      and the shoot. This review examines these signaling mechanisms and their
      interactions with sugar-sensing and hormonal response pathways.

PMID- 12221974
TI  - Acclimative response to temperature stress in higher plants: approaches of gene
      engineering for temperature tolerance.
AB  - Temperature stresses experienced by plants can be classified into three types:
      those occurring at (a) temperatures below freezing, (b) low temperatures above
      freezing, and (c) high temperatures. This review outlines how biological
      substances that are deeply related to these stresses, such as heat-shock
      proteins, glycinebetaine as a compatible solute, membrane lipids, etc., and also
      detoxifiers of active oxygen species, contribute to temperature stress tolerance
      in plants. Also presented here are the uses of genetic engineering techniques to
      improve the adaptability of plants to temperature stress by altering the levels
      and composition of these substances in the living organism. Finally, the future
      prospects for molecular breeding are discussed.

PMID- 12221976
TI  - New insights into the regulation and functional significance of lysine metabolism
      in plants.
AB  - Lysine is one of the most limiting essential amino acids in vegetative foods
      consumed by humans and livestock. In addition to serving as a building block of
      proteins, lysine is also a precursor for glutamate, an important signaling amino
      acid that regulates plant growth and responses to the environment. Recent
      genetic, molecular, and biochemical evidence suggests that lysine synthesis and
      catabolism are regulated by novel concerted mechanisms. These include
      intracellular compartmentalization of enzymes and metabolites, complex
      transcriptional and posttranscriptional controls of genes encoding enzymes in
      lysine metabolism during plant growth and development, as well as interactions
      between different metabolic fluxes. The recent advances in our understanding of
      the regulation of lysine metabolism in plants may also prove valuable for future
      production of high-lysine crops.

PMID- 12221975
TI  - Salt and drought stress signal transduction in plants.
AB  - Salt and drought stress signal transduction consists of ionic and osmotic
      homeostasis signaling pathways, detoxification (i.e., damage control and repair)
      response pathways, and pathways for growth regulation. The ionic aspect of salt
      stress is signaled via the SOS pathway where a calcium-responsive SOS3-SOS2
      protein kinase complex controls the expression and activity of ion transporters
      such as SOS1. Osmotic stress activates several protein kinases including mitogen
      activated kinases, which may mediate osmotic homeostasis and/or detoxification
      responses. A number of phospholipid systems are activated by osmotic stress,
      generating a diverse array of messenger molecules, some of which may function
      upstream of the osmotic stress-activated protein kinases. Abscisic acid
      biosynthesis is regulated by osmotic stress at multiple steps. Both ABA-dependent
      and -independent osmotic stress signaling first modify constitutively expressed
      transcription factors, leading to the expression of early response
      transcriptional activators, which then activate downstream stress tolerance
      effector genes.

PMID- 12221977
TI  - The lipoxygenase pathway.
AB  - Lipid peroxidation is common to all biological systems, both appearing in
      developmentally and environmentally regulated processes of plants. The
      hydroperoxy polyunsaturated fatty acids, synthesized by the action of various
      highly specialized forms of lipoxygenases, are substrates of at least seven
      different enzyme families. Signaling compounds such as jasmonates, antimicrobial
      and antifungal compounds such as leaf aldehydes or divinyl ethers, and a plant
      specific blend of volatiles including leaf alcohols are among the numerous
      products. Cloning of many lipoxygenases and other key enzymes within the
      lipoxygenase pathway, as well as analyses by reverse genetic and metabolic
      profiling, revealed new reactions and the first hints of enzyme mechanisms,
      multiple functions, and regulation. These aspects are reviewed with respect to
      activation of this pathway as an initial step in the interaction of plants with
      pathogens, insects, or abiotic stress and at distinct stages of development.

PMID- 12221978
TI  - Plant responses to insect herbivory: the emerging molecular analysis.
AB  - Plants respond to herbivore attack with a bewildering array of responses, broadly
      categorized as direct and indirect defenses, and tolerance. Plant-herbivore
      interactions are played out on spatial scales that include the cellular
      responses, well-studied in plant-pathogen interactions, as well as responses that
      function at whole-plant and community levels. The plant's wound response plays a
      central role but is frequently altered by insect-specific elicitors, giving
      plants the potential to optimize their defenses. In this review, we emphasize
      studies that advance the molecular understanding of elicited direct and indirect
      defenses and include verifications with insect bioassays. Large-scale
      transcriptional changes accompany insect-induced resistance, which is organized
      into specific temporal and spatial patterns and points to the existence of
      herbivore-specific trans-activating elements orchestrating the responses. Such
      organizational elements could help elucidate the molecular control over the
      diversity of responses elicited by herbivore attack.

PMID- 12221979
TI  - Phytochromes control photomorphogenesis by differentially regulated, interacting
      signaling pathways in higher plants.
AB  - In this review the kinetic properties of both phytochrome A and B measured by in
      vivo spectroscopy in Arabidopsis are described. Inactivation of phyA is mediated
      by destruction and that of phyB by fast dark reversion. Recent observations,
      describing a complex interaction network of various phytochromes and
      cryptochromes, are also discussed. The review describes recent analysis of light
      dependent nuclear translocation of phytochromes and genetic and molecular
      dissection of phyA- and phyB-mediated signal transduction. After nuclear
      transport, both phyA- and phyB-mediated signal transduction probably include the
      formation of light-dependent transcriptional complexes. Although this hypothesis
      is quite attractive and probably true for some responses, it cannot account for
      the complex network of phyA-mediated signaling and the interaction with the
      circadian clock. In addition, the biological function of phytochromes localized
      in the cytosol remains to be elucidated.

PMID- 12221980
TI  - The complex fate of alpha-ketoacids.
AB  - Plant cells are unique in that they contain four species of alpha-ketoacid
      dehydrogenase complex: plastidial pyruvate dehydrogenase, mitochondrial pyruvate
      dehydrogenase, alpha-ketoglutarate (2-oxoglutarate) dehydrogenase, and branched
      chain alpha-ketoacid dehydrogenase. All complexes include multiple copies of
      three components: an alpha-ketoacid dehydrogenase/decarboxylase, a dihydrolipoyl
      acyltransferase, and a dihydrolipoyl dehydrogenase. The mitochondrial pyruvate
      dehydrogenase complex additionally includes intrinsic regulatory protein-kinase
      and -phosphatase enzymes. The acyltransferases form the intricate geometric core
      structures of the complexes. Substrate channeling plus active-site coupling
      combine to greatly enhance the catalytic efficiency of these complexes. These
      alpha-ketoacid dehydrogenase complexes occupy key positions in intermediary
      metabolism, and a basic understanding of their properties is critical to genetic
      and metabolic engineering. The current status of knowledge of the biochemical,
      regulatory, structural, genomic, and evolutionary aspects of these fascinating
      multienzyme complexes are reviewed.

PMID- 12221981
TI  - Molecular genetics of auxin signaling.
AB  - The plant hormone auxin is a simple molecule similar to tryptophan, yet it
      elicits a diverse array of responses and is involved in the regulation of growth
      and development throughout the plant life cycle. The ability of auxin to bring
      about such diverse responses appears to result partly from the existence of
      several independent mechanisms for auxin perception. Furthermore, one prominent
      mechanism for auxin signal transduction involves the targeted degradation of
      members of a large family of transcriptional regulators that appear to
      participate in complex and competing dimerization networks to modulate the
      expression of a wide range of genes. These models for auxin signaling now offer a
      framework in which to test how each specific response to auxin is brought about.

PMID- 12221982
TI  - Rice as a model for comparative genomics of plants.
AB  - Rapid progress in rice genomics is making it possible to undertake detailed
      structural and functional comparisons of genes involved in various biological
      processes among rice and other plant species, such as Arabidopsis. In this
      review, we summarize the current status of rice genomics. We then select two
      important areas of research, reproductive development and defense signaling, and
      compare the functions of rice and orthologous genes in other species involved in
      these processes. The analysis revealed that apparently orthologous genes can also
      display divergent functions. Changes in functions and regulation of orthologous
      genes may represent a basis for diversity among plant species. Such comparative
      genomics in other plant species will provide important information for future
      work on the evolution of higher plants.

PMID- 12221983
TI  - Root gravitropism: an experimental tool to investigate basic cellular and
      molecular processes underlying mechanosensing and signal transmission in plants.
AB  - The ability of plant organs to use gravity as a guide for growth, named
      gravitropism, has been recognized for over two centuries. This growth response to
      the environment contributes significantly to the upward growth of shoots and the
      downward growth of roots commonly observed throughout the plant kingdom. Root
      gravitropism has received a great deal of attention because there is a physical
      separation between the primary site for gravity sensing, located in the root cap,
      and the site of differential growth response, located in the elongation zones
      (EZs). Hence, this system allows identification and characterization of different
      phases of gravitropism, including gravity perception, signal transduction, signal
      transmission, and curvature response. Recent studies support some aspects of an
      old model for gravity sensing, which postulates that root-cap columellar
      amyloplasts constitute the susceptors for gravity perception. Such studies have
      also allowed the identification of several molecules that appear to function as
      second messengers in gravity signal transduction and of potential signal
      transducers. Auxin has been implicated as a probable component of the signal that
      carries the gravitropic information between the gravity-sensing cap and the
      gravity-responding EZs. This has allowed the identification and characterization
      of important molecular processes underlying auxin transport and response in
      plants. New molecular models can be elaborated to explain how the gravity signal
      transduction pathway might regulate the polarity of auxin transport in roots.
      Further studies are required to test these models, as well as to study the
      molecular mechanisms underlying a poorly characterized phase of gravitropism that
      is independent of an auxin gradient.

PMID- 12221984
TI  - Rubisco: structure, regulatory interactions, and possibilities for a better
      enzyme.
AB  - Ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase (Rubisco) catalyzes the
      first step in net photosynthetic CO2 assimilation and photorespiratory carbon
      oxidation. The enzyme is notoriously inefficient as a catalyst for the
      carboxylation of RuBP and is subject to competitive inhibition by O2,
      inactivation by loss of carbamylation, and dead-end inhibition by RuBP. These
      inadequacies make Rubisco rate limiting for photosynthesis and an obvious target
      for increasing agricultural productivity. Resolution of X-ray crystal structures
      and detailed analysis of divergent, mutant, and hybrid enzymes have increased our
      insight into the structure/function relationships of Rubisco. The interactions
      and associations relatively far from the Rubisco active site, including
      regulatory interactions with Rubisco activase, may present new approaches and
      strategies for understanding and ultimately improving this complex enzyme.

PMID- 12221985
TI  - Shoot and floral meristem maintenance in arabidopsis.
AB  - The shoot apical meristem (SAM) of higher plants functions as a site of
      continuous organogenesis within which a small pool of pluripotent stem cells
      replenishes the cells incorporated into lateral organs. This article summarizes
      recent results demonstrating that the fate of stem cells in Arabidopsis shoot and
      floral meristems is controlled by overlapping spatial and temporal signaling
      systems. Stem cell maintenance is an active process requiring constant
      communication between neighboring groups of SAM cells. Information flows via a
      ligand-receptor signal transduction pathway, resulting in the formation of a
      spatial feedback loop that stabilizes the size of the stem cell population.
      Termination of stem cell activity during flower development is achieved by a
      temporal feedback loop involving both stem cell maintenance genes and flower
      patterning genes. These investigations are providing exciting insights into the
      components and activities of the stem cell regulatory pathway and into the
      interaction of this pathway with molecular mechanisms that control floral
      patterning.

PMID- 12221986
TI  - A new moss genetics: targeted mutagenesis in Physcomitrella patens.
AB  - The potential of moss as a model system to study plant biology is associated with
      their relatively simple developmental pattern that nevertheless resembles the
      basic organization of the body plan of land plants, the direct access to cell
      lineage analysis, their similar responses to plant growth factors and
      environmental stimuli as those observed in other land plants, and the dominance
      of the gametophyte in the life cycle that facilitates genetic approaches.
      Transformation studies in the moss Physcomitrella patens have revealed a totally
      unique feature for plants, i.e., that foreign DNA sequences integrate in the
      genome preferentially at targeted locations by homologous recombination, enabling
      for the first time in plants the application of the powerful molecular genetic
      approaches used routinely in bacteria, yeast, and since 1989, the mouse embryonic
      stem cells. This article reviews our current knowledge of Physcomitrella patens
      transformation and its unique suitability for functional genomic studies.

PMID- 12221987
TI  - Complex evolution of photosynthesis.
AB  - The origin of photosynthesis is a fundamental biological question that has eluded
      researchers for decades. The complexity of the origin and evolution of
      photosynthesis is a result of multiple photosynthetic components having
      independent evolutionary pathways. Indeed, evolutionary scenarios have been
      established for only a few photosynthetic components. Phylogenetic analysis of Mg
      tetrapyrrole biosynthesis genes indicates that most anoxygenic photosynthetic
      organisms are ancestral to oxygen-evolving cyanobacteria and that the purple
      bacterial lineage may contain the most ancestral form of this pigment
      biosynthesis pathway. The evolutionary path of type I and type II reaction center
      apoproteins is still unresolved owing to the fact that a unified evolutionary
      tree cannot be generated for these divergent reaction center subunits. However,
      evidence for a cytochrome b origin for the type II reaction center apoproteins is
      emerging. Based on the combined information for both photopigments and reaction
      centers, a unified theory for the evolution of reaction center holoproteins is
      provided. Further insight into the evolution of photosynthesis will have to rely
      on additional broader sampling of photosynthesis genes from divergent
      photosynthetic bacteria.

PMID- 12221988
TI  - Structure, dynamics, and energetics of the primary photochemistry of photosystem
      II of oxygenic photosynthesis.
AB  - Recent progress in two-dimensional and three-dimensional electron and X-ray
      crystallography of Photosystem II (PSII) core complexes has led to major advances
      in the structural definition of this integral membrane protein complex. Despite
      the overall structural and kinetic similarity of the PSII reaction centers to
      their purple non-sulfur photosynthetic bacterial homologues, the different
      cofactors and subtle differences in their spatial arrangement result in
      significant differences in the energetics and mechanism of primary charge
      separation. In this review we discuss some of the recent spectroscopic,
      structural, and mutagenic work on the primary and secondary electron transfer
      reactions in PSII, stressing what is experimentally novel, what new insights have
      appeared, and where questions of interpretation remain.

PMID- 12221989
TI  - Nonselective cation channels in plants.
AB  - Nonselective cation channels are a diverse group of ion channels characterized by
      their low discrimination between many essential and toxic cations. They are
      ubiquitous in plant tissues and are active in the plasma membrane, tonoplast, and
      other endomembranes. Members of this group are likely to function in low-affinity
      nutrient uptake, in distribution of cations within and between cells, and as
      plant Ca2+ channels. They are gated by diverse mechanisms, which can include
      voltage, cyclic nucleotides, glutamate, reactive oxygen species, and stretch.
      These channels dominate tonoplast cation transport, and the selectivity and
      gating mechanisms of tonoplast nonselective cation channels are comprehensively
      reviewed here. This review presents the first classification of plant
      nonselective cation channels and the first full description of nonselective
      cation channel candidate sequences in the Arabidopsis genome.

PMID- 12221990
TI  - Onchocerciasis (river blindness). Report from the eleventh InterAmerican
      conference on onchocerciasis, Mexico City, Mexico.

PMID- 12221991
TI  - Acrylamide in food (update).

PMID- 12221992
TI  - [Non-alcoholic steatohepatitis].

PMID- 12221993
TI  - [Scientific evidence in clinical practice: cost-effective and guaranteed quality
      of care].
AB  - According to the literature quality improvement methods were implemented
      successfully under various circumstances in many countries, through almost
      countless ways in order to achieve diverse quality improvement goals. Evidence
      suggests that quality improvement can be achieved through appropriate
      implementation of various methods. Literature on the effects of quality assurance
      on cost is relatively limited in number, however, the relation between the cost
      and quality is an issue of universal interest. Without any public consensus about
      what is meant by either quality or cost containment, it is difficult to evaluate
      their relation to each other fairly. However, there is sufficient support for the
      hypothesis that it is not too much quality, but rather too low quality that
      creates costs.

PMID- 12221994
TI  - [Anticipation in familial malignant hematologic diseases (epidemiologic
      observations)].
AB  - Between January 1 1983 and December 31 2000, 21 cases of association of
      haematologic malignancies between parents and their children, two cases of that
      in grandparents and their grandchildren, and five cases of appearances of
      haematologic malignancies in uncle or aunt and their nephew or niece were
      experienced by authors. The diseases manifested in the second (or in the third)
      generation in 25/28 cases appeared earlier than those in the first generation,
      and in 13/28 cases had a greater malignity. In the remaining 15 cases the
      malignity was identical in both generation. Instead of anticipation (greater
      severity and/or earlier onset) the term dual acceleration (earlier onset and
      greater malignity) is more exact and thus more proper determine epidemiologic
      observations of authors. Dual acceleration was proved by authors not only in
      identical but in different haematologic malignancies manifested both in first
      degree and second-degree relatives.

PMID- 12221996
TI  - [Non-alcoholic steatohepatitis: a childhood case].
AB  - INTRODUCTION: A significant part of cryptogenic cirrhosis among adult patients
      shows that it can be the result of "burn-out" non-alcoholic steatohepatitis
      beginning in childhood. AIM: Describing the case of a 15-year-old boy the aim of
      the authors is to raise attention to the fact that doctors should think of the
      possibility of having a fatty liver in presence of certain etiological features.
      PATIENT: Although he was asymptomatic, the screening test revealed an elevated
      serum aspartate aminotransferase level. Abdominal ultrasound examination raised
      the possibility of a diffuse liver damage. The liver biopsy demonstrated the
      features of steatosis in the absence of alcohol abuse. RESULTS: On the basis of
      these results, NASH was diagnosed. The presence of a severe fatty liver at such
      an early age is quite unusual. In the background, the authors verified familial
      combined hyperlipidaemia and heterozygous mutation of the cystic fibrosis gene
      for delta F508 as genetic predisposing factor. The clinical condition was
      accelerated and worsened by the fact, that the patient has grown fat since his
      infancy. It did not prove possible to achieve a weight reduction with a fat- and
      cholesterol-poor diet, increased physical activity and medical treatment.
      However, there was significant improvement in the laboratory findings.
      CONCLUSIONS: The conclusion drawn from this case, on one hand, is that doctors
      should think of the possibility of a fatty liver in case of an elevated isolate
      serum transaminase level in connection with obese or over weight patients. On the
      other hand the role of other coexisting etiological features must emerge in the
      background of severe steatohepatitis.

PMID- 12221995
TI  - [Hungarian adaptation of a disease-specific quality-of-life questionnaire in
      patients with ankylosing spondylitis].
AB  - INTRODUCTION: Measuring quality of life has growing importance in the field of
      health technology assessment. It is especially true for chronic diseases, like
      ankylosing spondylitis, which results in significant impact on patients' quality
      of life through the intensity and duration of the disease. OBJECTIVES: To measure
      the reliability and validity of the Hungarian version of Ankylosing Spondylitis
      Quality of Life instrument with the intention of its use in clinical and health
      economic trials and burden of disease studies in Hungary via the introduction of
      a certain validation process. METHODS: One of the most important criteria for the
      validity of quality of life instruments is the standard method used for adapting
      the questionnaire to foreign languages. The dual method was applied for the
      Hungarian adaptation of the Ankylosing Spondylitis Quality of Life questionnaire,
      which was followed by psychometric testing. RESULTS: High test-retest correlation
      (0.85) indicated an acceptable degree of reliability with no evidence of
      excessive random measurement error. The internal consistency of the measure was
      confirmed (Cronbach's alpha coefficients were 0.87 and 0.91 at Time 1 and Time 2
      respectively), with strong evidence that all items were adequately inter-related.
      The correlations with the NHP at both time points were at the expected levels,
      providing evidence of convergent and divergent validity. CONCLUSION: On the basis
      of results shown above, it is concluded that the Hungarian Ankylosing Spondylitis
      Quality of Life questionnaire is a reliable and valid measure of quality of life.

PMID- 12221997
TI  - [Jakab Pal (1863-1936)].

PMID- 12221998
TI  - WHO's response to the threat of the deliberate use of biological and chemical
      agents to cause harm.

PMID- 12221999
TI  - Locally delivered antimicrobials in periodontal treatment.
AB  - The management of periodontal diseases has included both non-surgical and
      surgical treatment options. Non-surgical treatment traditionally has referred to
      the role of mechanical instrumentation of the root surface with either scalers or
      curettes. However, the introduction of locally delivered anti-microbial
      medications, which can be placed directly into a periodontal pocket, has provided
      the practitioner with another treatment option. This article looks at the
      different locally delivered anti-microbial medications being used in the non
      surgical management of periodontal diseases.

PMID- 12222000
TI  - Periodontal disease and systemic disease. Clinical information for the practicing
      dentist.
AB  - The relationship between periodontal and systemic disease, previously called the
      "focal infection theory" or "focus of infection," has become an exciting area of
      clinical and laboratory research. Periodontal disease has been reported to
      influence diabetes mellitus, cardiovascular disease, osteoporosis, and
      respiratory disease. It also can influence the course and duration of pregnancy.
      This article reviews some of these associations and proposed mechanisms by which
      periodontal disease and systemic conditions influence each other. We also discuss
      clinical implications for our daily practice in dentistry.

PMID- 12222001
TI  - Recent advances in non-surgical and surgical periodontics.
AB  - The role of periodontal surgery in the management of periodontal diseases has
      continued to develop and benefit from advances in clinical as well as basic
      science research. The periodontist now has a wide variety of surgical treatment
      options to help patients who present with the manifestations of periodontal
      disease. This article looks at the surgical treatment modalities that are
      currently being used in clinical practice. In addition, it looks at the role of
      genetic testing in the overall patient management sequence.

PMID- 12222002
TI  - The role of periodontal maintenance in dental practice.
AB  - Periodontal maintenance therapy is dependent both upon methods of disease control
      that are either patient or therapist applied as well as on compliance with
      regular recall schedules. Recent advances in the design and use of mechanical
      aids for plaque removal, electric toothbrush design, use of chemotherapeutic
      plaque control agents, and evaluations of the role of maintenance therapy in
      practice are included. Numerous studies indicate that compliance with recall
      intervals may be difficult to achieve but is essential to the success of
      periodontal therapy. Suggestions for approaches to effective periodontal
      maintenance therapy are provided.

PMID- 12222003
TI  - Periodontics: new understanding, new treatment options.

PMID- 12222004
TI  - Small fix reaps big rewards.

PMID- 12222005
TI  - One-stop shopping for health care software. Single-source strategies.

PMID- 12222006
TI  - CIOs making soft sell when calculating ROI.

PMID- 12222008
TI  - Let the games begin: healthcare skirmishes and campaign 2002.

PMID- 12222007
TI  - The jury's still out on ASPs in health care.

PMID- 12222009
TI  - Pursue front-end solutions to revenue cycle problems, urges Davis.

PMID- 12222010
TI  - Measuring strategic success.
AB  - Strategic triggers and metrics help healthcare providers achieve financial
      success. Metrics help assess progress toward long-term goals. Triggers signal
      market changes requiring a change in strategy. All metrics may not move in
      concert. Organizations need to identify indicators, monitor performance.

PMID- 12222011
TI  - Effective claims denial management enhances revenue.
AB  - Claims denial management can enhance revenue in times of declining payment and
      increasing cost pressures. Denials usually arise from process problems leading to
      inadequate documentation. A denial management team should oversee prospective
      prevention and claims recovery. Prospective prevention minimizes denials by
      defining scope of service, tracking causes for denials, and improving related
      processes. Claims recovery improves chances of recovering denied payment.

PMID- 12222012
TI  - Assessing the cost-effectiveness of provider-based status.
AB  - Clinics with provider-based status often receive greater Medicare payments.
      Coinsurance costs are higher with provider-based status. Operational changes may
      be necessary to satisfy provider-based status requirements. Hospitals should
      identify potential payment increases and associated costs to determine whether
      provider-based status is cost-effective. If provider-based status is desirable,
      hospitals should make sure the government's guidelines and regulatory deadlines
      are met.

PMID- 12222013
TI  - Medicare's ambulance fee schedule dispatched.
AB  - Ambulance fees vary with the level of service and length of the beneficiary's
      trip. New fee schedule is expected to trim Medicare spending. Higher fees have
      been implemented for rural transports and air ambulance services. Lower fees have
      been implemented for urban transports. Providers and suppliers must revise
      chargemasters, policies, and procedures.

PMID- 12222014
TI  - Preserving IME (indirect medical education) payments.
AB  - Amended regulation reduces IME funding. Policy excludes residents' research time
      from IME formula. Policy will significantly reduce payments to many teaching
      hospitals. Hospitals should appeal based on various legal grounds. Hospitals
      could seek legislative relief.

PMID- 12222015
TI  - Using organizational change to reach your technology goals.

PMID- 12222016
TI  - Disaster planning for treasury management continuity.

PMID- 12222017
TI  - Restorative management of the worn dentition: 3. Localized posterior toothwear.
AB  - In the management of localized posterior occlusal toothwear, care must be taken
      not only in determining whether the worn teeth are restorable, but also the
      desirable occlusal scheme. Assessments of the periodontal, endodontic, and
      coronal tooth tissues, and the occlusal relationship are necessary for a
      comprehensive treatment plan for worn posterior teeth.

PMID- 12222018
TI  - Multiple sclerosis and oral care.
AB  - Multiple sclerosis is a complex neurological condition affecting sensory and
      motor nerve transmission. Its progression and symptoms are unpredictable and vary
      from person to person as well as over time. Common early symptoms include visual
      disturbances, facial pain or trigeminal neuralgia and paraesthesia or numbness of
      feet, legs, hands and arms. These, plus symptoms of spasticity, spasms, tremor,
      fatigue, depression and progressive disability, impact on the individual's
      ability to maintain oral health, cope with dental treatment and access dental
      services. Also, many of the medications used in the symptomatic management of the
      condition have the potential to cause dry mouth and associated oral disease.
      There is no cure for multiple sclerosis, and treatment focuses on prevention of
      disability and maintenance of quality of life. Increasingly a multi-disciplinary
      team approach is used where the individual, if appropriate his/her carer, and the
      specialist nurse are key figures. The dental team plays an essential role in
      ensuring that oral health impacts positively on general health.

PMID- 12222019
TI  - Auxiliary retention and the role of the core in fixed prosthodontics.
AB  - Extensively damaged teeth frequently require placement of a core before
      preparation to receive an indirect restoration. Dentine pins have traditionally
      been used to enhance retention and resistance form when coronal dentine is
      significantly reduced; however, pins are invasive and may produce pulpal or
      periodontal problems. Cavity design features such as grooves, boxes or retentive
      pits may be better alternatives. The choice of the core material may also
      influence the outcome although reliable research data are scarce. Large cores
      should be considered to have a structural role in supporting the final
      restoration.

PMID- 12222020
TI  - Management of dental unit water lines.
AB  - Dental unit water lines harbour considerable amounts of bacteria, derived from
      the biofilm on their inner surfaces, and the continuous reservoir of bacteria
      carries the potential to infect patients and dental workers alike. This article
      reviews the different methods of control and provides recent recommendations for
      ensuring that water of satisfactory quality is delivered to the patient.

PMID- 12222021
TI  - Rapid correction of anterior crossbite using a fixed appliance: a case report.
AB  - Anterior crossbite is a commonly encountered problem that is traditionally
      managed with removable appliances. This paper demonstrates some of the advantages
      of using fixed appliances to correct these malocclusions. In this case, treatment
      was completed more rapidly than would have occurred with conventional techniques.

PMID- 12222022
TI  - A single-appointment, definitive post-crown restoration: a case report.
AB  - The marked advances made in restorative materials have allowed dentists to
      explore new techniques in restoring teeth. This paper describes a method of
      restoring extensively damaged endodontically treated teeth that are using the
      LightPost system and composite resin to build-up the broken crown directly. The
      treatment was completed in a single visit. Applying this direct technique in
      selected cases can simplify treatment planning and result in an acceptable
      restoration with pleasing aesthetics.

PMID- 12222023
TI  - Proud to be a dinosaur.

PMID- 12222024
TI  - Solving a conundrum.

PMID- 12222025
TI  - Case report of an unusual foreign body in the oral cavity.

PMID- 12222026
TI  - Physician compensation, productivity still on the rise.

PMID- 12222027
TI  - Check out these integrated health system utilization benchmarks.

PMID- 12222028
TI  - Pennsylvania HMOs demonstrate that prevention works.

PMID- 12222029
TI  - [The job of the hospital nurse: self-care and caring for others].
AB  - The self-care of nurses is a requirement for the care of the patient, so that the
      care provided will not imply on the resignation of the nursing professional or
      the client. The objective of the present study is to verify how the work of
      hospital nurses has been done, regarding the self-care of these professionals and
      the care provided to patients. Semi-structured interviews were carried out with
      nurses from two different districts in Rio Grande do Sul, who had graduated from
      public universities in the same state and worked in hospitals of the respective
      districts. Results showed that these professionals expressed the need of taking
      care of themselves in order to provide care for their patients. It was also
      reported that nurses assume responsibilities of other professionals and lack, in
      their professional environment, human and material resources. This situation
      generates negative consequences for the nurse's self-care, as well as for the
      care of the patients. It is important that nursing professionals implement
      strategies to deal with asymmetric power relations in the hospital, based on
      their beliefs, values and knowledge. This can lead to more appropriate conditions
      of work, which can guarantee a more qualified self-care of the professional, and
      a better care for the patient.

PMID- 12222030
TI  - [Creating nursing knowledge in Brazil: research topics].
AB  - The present article discusses the themes that have orientated knowledge building
      in nursing in Brazil. The data was collected in post-graduation programs,
      graduation schools, university hospitals and indexed publications in LILACS and
      MEDLINE's database (1990-1999). Cardoso categorized the lines and areas of
      research according to a document created in nursing forums of discussion. The
      data was analyzed through a qualitative and quantitative approach, and presented
      in the form of graphics. Results indicate a shift on the lines/areas of research,
      especially in the case of researches that are indexed. It also demonstrates a
      special attention of this professional area to methodological references and
      paradigms that relate to the object of knowledge in nursing.

PMID- 12222031
TI  - [Significance of care for children and adolescents victims of domestic violence].
AB  - This is a phenomenological and hermeneutic study. Its objective is to reveal the
      meaning of "care" for children and adolescents who have suffered domestic
      violence. The investigation was carried out in two casas-lares (orphanage houses)
      in Florianopolis. These houses functioned as temporary shelters for either girls
      or boys who had suffered some kind of violence in their homes. The descriptions
      obtained through the answers and drawings of eighteen children and adolescents
      enabled us to characterize "care" as a way of promoting life, expressing oneself,
      relating to the environment, denying past experiences and resisting in order to
      survive.

PMID- 12222032
TI  - [Ethical behavior in the daily professional practice of nurses].
AB  - The daily practice of nurses is full of situations that demand a close analysis
      of the sociocultural context, so that the appropriate decisions are made. These
      decisions can either be of technical or ethical nature. In the present study, the
      authors reflect about the professional practice of nurses, focusing especially on
      the process of ethic decision making. They also relate these decisions to some of
      the ethic theoretical frameworks in order to indicate the references that guide
      the nurse's practices in the different professional situations.

PMID- 12222033
TI  - [Experiencing diversity through home care of the elderly--challenges and
      advances].
AB  - The present article is a study about the nursing care of elderly people. The
      diversity of experiences generated by the care of the elderly in their homes has
      opened news area of research, improved and promoted the nursing care. The
      objective of this work is to characterize the home-care of elderly as an area of
      interest for the work of the nursing professionals. The study describes aspects
      of the dynamics of this work based on a critical analysis of an experience
      carried out with a group of elderly and pointing out its advances and challenges.
      The methodology used in this investigation were records of the experience of some
      elderly people who had undergone surgery and were still in need of nursing care
      at their homes. Results show that there were improvements in terms of the nursing
      practices, especially the practices of educational and ethic-legal nature. The
      practices of educational nature could propitiate a sense of citizenship and
      freedom, which are prerogatives for the lives of these people. The ethic-legal
      practices promoted more involvement of the nursing professionals in the
      interdisciplinary team.

PMID- 12222034
TI  - [Health care models for nursing practice].
AB  - The focus of this study is the development and the choice of nursing models. It
      doesn't intend to discuss all the aspects involved in the development of models,
      but to emphasize the importance of choosing one to use in nursing clinical
      practice.

PMID- 12222035
TI  - [Nursing research projects in CNPQ (National Council for Scientific and
      Technologic Development): their trajectory, themes and adherences--1998/2000].
AB  - The present study analyses the themes proposed by research projects in nursing.
      It focuses on the projects that were sent to a Brazilian governmental research
      fomentation agency--CNPq--in the period of time between November 1998 and
      November 2000. The objective of this work is to identify the recurrent themes
      proposed in nursing research projects, and discuss its adherence to lines of
      research under study by nursing professionals which have the support of CAPES. It
      also relates these themes to the priorities of research established by CNPq. In
      order to achieve the objectives mentioned, an exploratory and descriptive study
      was carried out. The primary sources were evaluation grids of research projects.
      The secondary sources were studies, written and statistics reports from CNPq.
      Results show that most of the scholarships awarded by CNPq are in the southeast
      region of Brazil, where a larger number of researchers and post-graduation
      programs are concentrated. It also reveals that there is a diversity of themes
      being explored and that there is a relation between the themes and the parameters
      adopted for the studies.

PMID- 12222036
TI  - [The family health program and the reconstruction of basic health care in the
      Systema Unico de Saude: a contribution of Brazilian nursing].
AB  - The present study is a reflection about the historical, political and
      administrative dimensions of the reorganization of basic attention health
      services in Brazil, especially PSF and PACS. It also discusses the insertion of
      nursing professionals in these organizations, focusing on the management of total
      care in nursing assistance.

PMID- 12222037
TI  - [Bamboo rhizome system of mixed forest of Sassafras tsumu and Phyllostachys
      pubescens].
AB  - By the method of fixed plots, the bamboo rhizome system structure and nutrient
      content in rhizome from mixed Sassafras tsumu and Phyllostachys pubescens, which
      were established in 1983-1984 by planting S. tsumu on new-planted bamboo forests
      (3-4 years old), were investigated. The results showed that the mixtures with
      rational density of S. tsumu were suitable for optimizing the bamboo rhizome
      structure and increasing the nutrient content in rhizome. The total length and
      weight of rhizome, the diameter of rhizome and its evenness indices, the annual
      growth of new rhizome, the proportion of healthy rhizomes and buds, and the
      volume of rhizome system in the mixed bamboo forests with the density of 420-615
      S. tsumu trees per hectare were higher than those in pure bamboo forest,
      respectively. The indexes mentioned above in mixed bamboo forests with the
      density of S. tsumu more than 735 trees per hectare were lower than those in pure
      bamboo forest, respectively, but the frequency of rhizome branch per unit length
      of rhizome was obviously higher than that in pure bamboo forest. The results of
      regression analysis showed that there were close relationships between S. tsumu
      density and total length of rhizome, the length between two joints, the growth of
      new rhizome, the diameter of rhizome and its evenness indices, and the frequency
      of rhizome branch per unit length of rhizome. The content of N, P, K, Ca, and Mg
      in the rhizome from mixed bamboo forests were higher than those in pure bamboo
      forest, respectively. For example, the content of N in rhizomes from mixtures was
      increased by 7.6-11.6% averagely.

PMID- 12222038
TI  - [Microclimatic effect and soil moisture change of poplar-wheat intercropping
      systems in Huaibei Plain].
AB  - In this paper, the microclimatic effect and the soil moisture of poplar-wheat
      intercropping systems were studied. The results indicated that the strip
      intercropping, comparing with the contrast, could increase the relative humidity
      by 2-8%, decrease the surface temperature by 1-7 degrees C, and reduce wind
      speed. The illumination hours were decreased with the time and the distance
      between the rows, and the varying range was within 4.1-15.3%. In shelterbelt
      network, the relative humidity was increased by 6.4-11.6%, and the illumination
      hours were decreased by 8.5-11.7%. In strip intercropping, the intercropping
      systems could improve soil moisture, which was varied with the intensity of tree,
      and generally, the increase of soil moisture was about in a range of 0.67-3.87%.
      In shelterbelt network, the soil moisture was related to the orientation and the
      distance from the shelterbelt, and there existed negative correlation between the
      soil moisture and the distance in all orientations.

PMID- 12222039
TI  - [Physiological characteristics of resistance of different plum varieties to
      artificial adverse environments].
AB  - The relative electric conductivity, soluble sugar content in leaf, and POD
      activity of 17 plum varieties, which belong to six species and one genera, were
      measured under artificial adverse environments. The results showed that there
      were extreme significant negative correlation (alpha = 0.01) between soluble
      sugar content and membrane freezing damage, and significant negative correlation
      (alpha = 0.05) between POD activity in bark and leaf cell heat damage. According
      to Fuzzy synthetic evaluation, the comprehensive resistances of different plum
      varieties to adverse circumstances were discussed in this paper.

PMID- 12222040
TI  - [Architectural plasticity of the stoloniferous herb, Duchesnea indica in response
      to different elevation].
AB  - Architectural plasticity of clonal plant may modify its ways of utilization of
      resources through clonal growth and be of ecologically importance. The plasticity
      of clonal architecture in response to ecological conditions at different
      altitudes in a stoloniferous herb, Duchesnea indica, was investigated in an
      experiment with different elevations of 400, 800, 1200, and 1600 m. The results
      showed that the change patterns of spacer length, ramet density, branching
      intensity, and branching angle of Duchesnea indica were in a quadratic curve when
      the elevation increased. The architectural plasticity of D. indica was simulated
      through dynamic Logistic model, and the imitative effect was statistically
      preferable. Combining with the resources utilization of Duchesnea indica under
      different environments, the architectural plasticity was also discussed in this
      paper.

PMID- 12222041
TI  - [Landscape structure of the farming-pastoral zone based on Landsat-TM data--a
      case study of Xinghe County, Inner Mongolia].
AB  - Xinghe County, Inner Mongolia, belongs to the typical region of farming-pastoral
      zone in northern China and is chosen as a case study area in this paper. Based on
      the interpretation of the Landsat-TM data (with two digital images taken in 1989
      and 2000, respectively), the landscape structure was studied by analyzing patch
      size, spatial pattern, and other index to show the changing feature of landscape
      pattern. The results showed that farmlands and grasslands were the main landscape
      types in plain and hilly land of the County, and different landscape types had
      different scales of landscape patch-size. The patch-sizes of farmland and
      grassland had been apparently expanded from 1989 to 2000, while those of the
      forestland and waters had been shrunk. The landscape pattern had an obvious trend
      of fragmentation due to human activities.

PMID- 12222042
TI  - [Seeping irrigation effect in sunlight greenhouse].
AB  - The differences of soil and air environments, crop growth, development and
      diseases, and water use efficiency of seeping irrigation from furrow irrigation
      were studied. Results indicated that compared with furrow irrigation, seeping
      irrigation could increase soil waterstable granular by 81.4%, soil porosity by
      29.0% and soil temperature by 1.1-1.7 degrees C respectively, decrease bulk
      density by 21.2% and relative air humidity by 13.4% respectively, and save
      irrigation water by 36.7%. In addition, seeping irrigation could also accelerate
      crop maturity and increase yield, reduce crop diseases and production cost.
      Therefore, seeping irrigation was an ideal irrigation technique in sunlight
      greenhouse at present.

PMID- 12222043
TI  - [Effect of clipping at seedling stage on growth and yield of spring wheat].
AB  - The compensation for spring wheat (Triticum aestivum) under simulated herbivory
      stress by clipping was examined in a semi-arid region of Gansu province in 1996.
      The results showed that clipping at seedling stage reduced spring wheat growth
      under two irrigation conditions. The yield of spring wheat generally under
      compensated the clipping effect. Heavy clipping (cutting all leaves above the
      ground, T0, T1) resulted in a more serious reduction in yield, compared with
      light clipping cutting half of the leaves, H0, H1). The yields of all treatments
      were lower than controls(CK0, CK1), i.e., CK0 > H0 > T0 > CK1 > H1 > T1.
      Irrigation for once right after clipping increased wheat growth and its
      compensatory ability, although they were still under-compensation.

PMID- 12222044
TI  - [Dynamics of beta-glucan content during kernel development and its relationship
      with meteorological factors].
AB  - The dynamics of beta-glucan content of two barley varieties during kernel
      development phase and the effect of some meteorological factors on beta-glucan
      content were studied. The results showed that beta-glucan content in kernel is
      both dominated by genotype and influenced by meteorological factors. The model of
      dynamic during kernel development phase is very similar in both barley varieties,
      but differs in years greatly. It is showed that the dynamic of beta-glucan
      content during kernel development phase is completely consistent with those of
      kernel-weight increase and protein accumulation per grain. The dynamic of beta
      glucan content in barley kernel is significantly influenced by meteorological
      factors, and there is significantly negative relationship between accumulated
      temperature during kernel development phase and beta-glucan content in kernel.

PMID- 12222045
TI  - [Comparison of morphology, physiology and mineral element contents among
      genotypes of sesame with different tolerance to waterlogging under anaerobic
      condition].
AB  - The morphological and physiological indexes and the mineral element contents in
      different organs of 4 genotypes of sesame were examined under controlled oxygen
      supply. The number of adventitious roots of flooding tolerant varieties, Wild No.
      7 and Yuzhi No. 1, increased 4-5 fold, the activity of ADH enhanced about twice,
      but the net photosynthetic rate (Pn) decreased slightly. There were significant
      increase in Ca and P and little decrease in K in roots, and decrease in other
      elements in roots and 8 elements in stems and leaves. As for less flooding
      tolerant genotypes, Danbackaggce and Suiping Xiaozhihuang, however, the number of
      adventitious roots increased little, the activity of ADH enhanced 5-9 folds, and
      Pn decreased by 50-60%. An increase in Ca and P, and a significant reduction in K
      was found in roots. It was concluded that the waterlogging tolerance of sesame
      depended firstly on the structural adaptation, then on the anoxia metabolism, and
      that Ca and P may play an important role in the metabolic adaptation to the
      anaerobic environment for plant survival.

PMID- 12222046
TI  - [Characteristics of functional and nutritious soilless culture substrate for
      vegetables].
AB  - A functional and nutritious substrate for soilless culture, which consists of
      peanut shell, sawdust, vermiculite, chicken manure, coal cinder, etc, was used to
      grow cucumbers, tomatoes and peppers in this experiment. The results showed that
      the substrate was rich in organic matter, N, available P and K, in which the
      nutrients were basically in balance for three vegetables. High content of
      microorganisms and high activity of soil enzymes were propitious to the
      transformation of organic components in the substrate. The yields of cucumber,
      tomato and pepper increased by 23.83%, 27.34% and 32.98%, respectively. The
      production value of peppers increased by 180.85%, and its net income increased by
      109.69%. The qualities of three vegetables were coincident with 'harmless
      vegetable' standards.

PMID- 12222047
TI  - [Ecophysiological effects of CO2 enrichment on bottle gour in plastic house].
AB  - In vegetable growing under protection, lack of carbon dioxide is one of the most
      important factors limiting photosynthesis. The application of 600-1200 mumol.mol
      1 CO2 in the plastic house increased photosynthetic rates and ratio of C/N,
      promoted both vegetative and reproductive growth of bottle gourd plants. Plant
      height, stem diameter, leaf thickness and leaf area increased by 3.90-19.48%,
      11.58-27.37%, 38.46-69.23% and 26.09-49.38%, respectively. Average single fruit
      weight and yield were 4.05-19.62% and 8.65-19.47% higher than that in normal air.
      Primary female flower position was lowered by 2.6-4.0. Net photosynthetic rate
      and the carboxylase activity of RuBP were greatest under CO2 1000 mumol.mol-1.
      The optimal concentration of CO2 applied to bottle gourd in spring was about 1000
      mumol.mol-1.

PMID- 12222048
TI  - [Effect of mutual interference and spatial heterogeneity on predation of adult
      Chrysopa septempunctata].
AB  - The more wheat stalks the adult Chrysopa septempunctata encountered, the more
      interference was met during the predation of C. septempunctata, which means that
      the predation efficiency was low when the spatial heterogeneity was complex. The
      coefficient of mutual interference within C. septempunctata was 0.9390, and that
      between C. septempunctata and Propylaea japonica was 0.8722. The frontier was
      greater than the latter. The correlation of competition strength(I) and the
      number of natural enemy (P) could be described as I = 0.0640 + 1.1127 1gP.

PMID- 12222049
TI  - [Effects of cumulative parthenogenetic generation and age of amictic female on
      the reproduction of rotifer Brachionus calyciflorus].
AB  - Effects of cumulative parthenogenetic generation and age of amictic female on
      mictic female production and fecundity of the rotifer Brachionus calyciflorus
      were studied by means of individual culture. The results showed that percentage
      of total mictic females produced by the parental females in each of four
      generations increased with the increasing generations. More mictic females were
      produced from younger maternal amictic females. Amictic offspring from older
      mothers produced more mictic daughters. There was no significant effect of the
      cumulative parthenogenetic generation on the mean number of eggs produced by
      amictic females per life cycle, and no significant effect of the age of amictic
      female on the mean number of eggs produced by the offspring of amictic female.

PMID- 12222050
TI  - [Variation in the viability and the metabolism of internally reserved nutrients
      of Beauveria bassiana conidia during storage at different regimes of water
      content and temperature].
AB  - While the fresh powder (with water content of 58.9 +/- 1.6%) and vacuum-freeze
      dried (VFD) one (with water content of 7.4 +/- 0.9%) of Beauveria bassiana
      SGBB8702 conidia were stored at 4 degrees C and 20 degrees C, their viability and
      contents of internally reserved saccharides and proteins were examined at 5 days
      intervals. It was found during one-month storage that the water content and
      temperature interactively affected the levels of conidia viability and the
      contents of the reserved saccharides and proteins, which in turn correlated
      considerably well to the viability. Stored at 4 degrees C and 20 degrees C, the
      VFD conidia lost content of saccharides by 13.4% and 14.1%, content of proteins
      by 39.2% and 38.2%, and viability by 32.0% and 55.8% when germinating in water
      only and 6.7% and 10.4% when germinating in 2% glucose solution plus 0.5%
      peptone, respectively. In contrast, the four estimates of the fresh conidia
      stored at 4 degrees C and 20 degrees C decreased by 42.4% and 43.2%, 66.3% and
      65.4%, 96.4% and 99.4%, and 9.9% and 98.4%, respectively. Thus, water content of
      B. bassiana conidia affected variation ranges of the viability and the internally
      reserved nutrients whereas storage temperature influenced their variation rates.
      However, depletion of the internally reserved nutrients did not necessarily
      inactivate the conidia. Instead, such conidia may germinate at relatively high
      level during a period of time as long as being supplied with sufficient
      nutrients. In another experiment, the powder of VFD conidia with water content
      being reduced to 4.0 +/- 0.9% were half-monthly examined for viability during one
      year storage. The viability only decreased slightly from 99.0% to 90.2% at 4
      degrees C by the end of one year. Stored at 20 degrees C, the viability also
      declined slowly during the first 165 days but dramatically decreased afterwards
      with little being detected on day 240. A modeling analysis showed that the time
      for the VFD conidia to lose 50% viability was 1006 days at 4 degrees C and 197
      days at 20 degrees C, respectively. Conclusively, the B. bassiana conidia powder,
      even though its water content was controlled below 5%, can be safely stored for
      one year or longer at low temperature only but for no longer than 6 months at
      ambient temperature.

PMID- 12222052
TI  - [Spatial heterogeneity of grassland pattern under grazing and forage condition].
AB  - Spatial heterogeneity and spatial autocorrelation of grassland pattern under
      grazing and forage condition were studied using semivariance analysis and fractal
      method. The results indicate that vegetation patterns are scale-dependent.
      Spatial heterogeneity and spatial autocorrelation of foraged grassland are more
      complex than grazed grassland and have more scale regions which determined by
      different fractal characteristics. Spatial autocorrelation of species diversity
      on foraged grassland was weaker, in another word, gradient of species
      diversity(beta-diversity) was smaller. Spatial heterogeneity of grazed grassland
      was simplified by grazing, because topographical variation was partly wiped out.

PMID- 12222051
TI  - [Integrated control of main diseases and insects of Dendranthema morifolium].
AB  - The main virus diseases, downy mildew, leaf spot, leaf-injuring insects and
      aphid's natural enemies in Dendranthema morifolicum were investigated and
      identified, and the development laws of pests and natural enemies were studied
      respectively. The effectiveness of integrated control of stem-tip culture, film
      covering, interplating with tall stalk crops, micronutrient application, terminal
      bud excising, and use of natural enemies were evaluated. The results showed that
      after the application of above integrated control measures, the virus-free rate
      and the yield-increasing rate of the seedlings from stem-tip culture were about
      60% and over 50%, respectively. The incidence of downy mildew and leaf-spot
      decreased by 28% to 30%. The injurious insect density reduced by 40%. The
      detection of pesticides residue indicated that three pyrethroids insecticides
      such as cypermethrin, fenvalterate, and deltamthrin were applied one month before
      harvest, the residues in Dendranthema morifolium after harvest were 0.017, 0.058
      and 0.019 mol.L-1, respectively, and all lower than the relevant tolerance
      values.

PMID- 12222053
TI  - [Difference between two wheat cultivars in Cd and mineral nutrient uptake under
      different Cd levels].
AB  - Cadmium pollution in soil not only affects growth and yield formation of crop
      plants, but also develops a potential risk to food health. The experiment was
      conducted to study growth of Cd and mineral nutrient uptake of two wheat
      cultivars differed in agronomic performance in seedling stage under 5 Cd levels
      ranged from 0 to 1.0 mg.kg-1 Cd. The results showed that the growth and dry
      matter accumulation were stimulated in low Cd concentration (0.03 mg.kg-1) for
      both cultivars, while inhibited significantly under high concentration (> 0.3
      mg.kg-1). The inhibited extension was dependence on cultivars and Genguo 534 had
      higher tolerance to Cd toxicity in comparison with E18513. There was the
      significant interaction between Cd level and cultivar in the influence of Cd
      treatment on Cd content in both root and shoot in that Genguo 534 had higher Cd
      content in lower Cd levels and E81513 showed more rapid increase in higher Cd
      levels. Cd treatment had significant influence on mineral nutrient uptake and two
      cultivars showed different response. In the treatment of 0.1 mg.kg-1 Cd, the
      contents of five macro-nutrients were significant lower for E81513 in comparison
      with those in control, while Genguo remained little changed.

PMID- 12222054
TI  - [Eco-toxicology of heavy metals on the inhibition of seed germination and root
      elongation of wheat in soils].
AB  - The eco-toxicity of Cu, Zn, Pb, and Cd in the single form was tested with four
      types of soils(red loam soils, meadow brown soils, chestnut soils, and dark brown
      soils) and their combined effect was determined with meadow brown soils. The
      results showed that with the same content of heavy metals, the root elongation
      was strongly inhabited than the seed germination, and it indicated that root was
      more sensitive to heavy metals pollution. The inhibition rate of heavy metals
      pollution on the root elongation (IRHMRE) of wheat was significantly related with
      the contents of organic matter (OR) and Kjedahl-nitrogen (K-N) in soils (R2OR =
      0.91, R2K-N = 0.92). However, IRHMRE was not significantly related with soil pH
      as did with OR and K-N, so does the content of CEC (R2pH = 0.62, R2CEC = 0.60).
      Whether under the low concentration of Cu, Zn, Pb, and Cd resulted in an
      irritated effect in root elongation, or under high concentration resulted in an
      inhibition effect in the single form, an synergistic effect occurred in the
      combined form.

PMID- 12222055
TI  - [Sewage sludge as fertilizer for grassland].
AB  - The experiment of sewage sludge composted as fertilizer for Zoysia japonica was
      conducted, and the results showed that Cd content in soil was lower than 0.3
      mg.kg-1 under the condition of the fertilizer application lower than 45 t.hm-2
      (dry weight) and the pH value of soil lower than 6.5 (Cd as the limiting factor
      for the amount of fertilizer application). NO3(-)-N content of groundwater was
      lower than the standard of the first class groundwater (10 mg.kg-1). The contents
      of organic matter, available N, total N, and total P were higher than those under
      control by 16%, 78%, 61%, and 140%, respectively. The biomass of Zoysia japonica
      was increased two times against the control. Therefore, sewage sludge utilized as
      fertilizer for grassland might be a valuable approach.

PMID- 12222056
TI  - [Changes of chemical and biological properties during composting sewage sludge by
      using forced aerated static pile model].
AB  - Municipal sewage sludge was composted for 53 days with Chinese medical herb
      residues as bulking agent through forced aerated static pile model. The
      temperature of the pile could quickly rise to more than 55 degrees C after the
      second day after composting. Furthermore, the temperature of more than 55 degrees
      C maintained as long as 8 days, which was helpful in inactivation of pathogens in
      compost. The cress seed germination index (GI) and the ratio of water-soluble
      organic carbon to organic nitrogen (soluble C/N-organic), used as indicators of
      phytotoxicity and maturation of compost, exhibited that the sludge compost was
      almost stabilized and matured near the 40th day of composting, when 80% of GI and
      6.4 of soluble C/N-organic were obtained. The content of total N, P, Cu, Zn and
      Cd in compost increased as the composting time elapsed, while volatile solids,
      solid and water soluble organic carbons, pH, and NH4(+)-N decreased. F. coli, as
      a common indicator of pathogens in sludge, was reduced greatly from 1.41 x 10(5)
      to 2.32 x 10(1) in the final examination of the compost.

PMID- 12222057
TI  - [Toxicity effect of substituted benzenes in oilfield wastewater by molecular
      orbital method].
AB  - The quantum parameters of energy of highest occupied molecular orbital (EHOMO),
      energy of lowest unoccupied molecular orbital (ELUMO), energy of next highest
      occupied molecular orbital (ENHOMO), energy of next lowest unoccupied molecular
      orbital (ENLUMO), heat of molecular formation(delta H0f) and dipole moment (mu)
      of 55 substituted benzenes are calculated based on MOPAC software of molecular
      orbital AM1 method. The QSAR model of multiple descriptors was established by the
      above parameters and the parameters of first-order valence-corrected molecular
      connectivity index (1Xv), octanol-water partition coefficient (logP), observed 30
      min-EC50 values of photobacteria. The QSAR model of 55 substituted benzenes was
      also established by two parameters of 1Xv and EHOMO. The toxicity mechanism of
      different substitutions was discussed. Results showed that the combination of
      quantum and physio-chemical parameters was very useful in predicting biological
      activity of substituted benzenes in oilfield wastewater. The quantum parameters
      were ideal parameters in describing the toxicity of organic compounds in oilfield
      wastewater.

PMID- 12222058
TI  - [Problems and trends of long-term ecological research].
AB  - Long-Term Ecological Research (LTER) has been focused on the monitoring and
      controlling the factors that influence the ecological process in a long period.
      The results are also the basis for the ecological assessment and management.
      Referring to the experiences of long-term research in international perspectives,
      this paper attempts to elucidate the problems, research contents, research trends
      and solutions of LTER with the expansion of temporal and spatial scales. It also
      has an instructive role in the long-term research, the construction of ecological
      research network and the terrestrial assessment in China.

PMID- 12222059
TI  - [Land-use strategy in riverine area].
AB  - The land near river is one kind of land zone that is inseparably related to the
      ecological process of river and lake, and directly affected or endangered by
      flood. Combined with ecological principles and the theory of forest eco-network
      system in China, the landscape security, the principles and directional thoughts,
      the theoretical basis and strategy were comprehensively studied in this paper.
      The landscape security should include three aspects of ecological benefit
      security, economical benefit security, and social benefit security. The land-use
      principles should be to find the best uniting section and ensure integration of
      the three principles together. The directional thoughts should be to combine
      management and development together, strengthen the landscape security by various
      measures, and carry out the near natural land-use and managing strategy by
      increasing the proportion of forest. Different development models should be
      selected in different rivers and regions. According to the risk grades of flood
      disturbance and spatial differentiation of lands near river, the different
      managing strategy with different disturbance degree should be carried out in
      different reach in upstream, midstream, and downstream based on the spatial
      differentiation of river and lands nearby in longitudinal direction, while based
      on the spatial differentiation and security during flood in cross direction, the
      utilization strategy should be classified and aimed at fragile use zone, stable
      use zone, and elastic use zone, respectively.

PMID- 12222060
TI  - [Assessment method of ecosystem health].
AB  - Ecosystem is the basic unit to maintain human environment. Ecosystem function
      mainly includes two aspects: ecosystem service function and goods function. These
      two functions are the basis for human living and development. Ecosystem health is
      the presupposition of ecosystem function. The completeness (structure and
      function), resilience, stability, and sustainability are the characteristics of
      ecosystem health. Ecosystem health assessment selects the indicator based on the
      ecosystem structure and function, including completeness, suitability, and
      effectiveness of ecosystem. Ecosystem health assessment mainly has two methods:
      one is indicator species assessment, and the other is structure and function
      index assessment which includes single index assessment, complex index
      assessment, and index system assessment which includes natural index system
      assessment and social-economic-natural index system assessment. In this paper,
      different assessment methods on ecosystem health are compared, and different
      health assessment method for different ecosystem types are also expatriated.

PMID- 12222061
TI  - [Effects of transgenic crops on soil ecosystem].
AB  - The effects of transgenic crops on the soil ecosystem were reviewed. The activity
      of Cry I Ab gene and proteinase inhibitor gene in the soil was summarized. The
      differences of soil microbes' components, soil enzyme activities, and soil fauna
      between genetic crops and isogenic strain crops were analyzed. According to
      current progress, the potential impacts of transgenic plant on soil
      microorganisms depend on the characteristics of the gene transferred into the
      crops and the soil properties. The change of soil ecosystem affected by many
      factors, and among them, the complex and stability of the ecosystem are the most
      important. The ecological effects of transgenic crops on the soil ecosystem need
      to be evaluated more fully before they are planted over extensive areas. Much
      effort should be devoted to the development of molecular techniques method to
      assess the effects of transgenic crops on soil ecosystem.

PMID- 12222062
TI  - [Review on landscape heterogeneity].
AB  - On the base of precedent studies, the occurring mechanism, classification,
      measurement methods, and the important role of landscape heterogeneity in
      landscape ecology were reviewed. The inner and outer uncertain factors result in
      landscape heterogeneity. Landscape heterogeneity has close relations with
      landscape stability, landscape design, architecture, management and disturbance,
      scale and ecological diversity in ecology. Complexity of landscape heterogeneity
      research, non-system of measurement indices and methods, difficulties and
      limitations of landscape heterogeneity modelling were all discussed respectively.
      In addition, it is suggested that the theory and methods of ecological complexity
      should be used to improve landscape heterogeneity research.

PMID- 12222063
TI  - [Behaviors of polycylic aromatic hydrocarbons (PAHs) in the soil].
AB  - Adsorption equilibrium of PAHs in the soil can be reached by two mainly
      processes, "quick" and "slow". Although PAHs with low molecular may be absorbed
      by the plant root, and transferred and transformed into other upper part of
      plant, the main accumulation pathway for PAHs in plant is from the air to the
      leaf surface. Microbial degradation of PAHs by its enzymatic capacity is the main
      process of the degradation of PAHs in nature. In addition, factors effecting the
      biodegradation of PAHs are analyzed in details in this review.

PMID- 12222064
TI  - [Phytogenic isoprene and its ecological significance].
AB  - Isoprene is the main component of numerous volatile hydrocarbons emitted by
      vegetation. Its biosynthesis and emission from vegetation plays an important role
      in global carbon balance, greenhouse effect, and atmospheric pollution. In this
      paper, the main factors determining isoprene emission rate, isoprene emission
      amount and its calculation methods, as well as its potential ecological functions
      were reviewed. The importance of further study on the relationships between
      multiple stresses and isoprene biosynthesis and emission was emphasized.

PMID- 12222065
TI  - [Response of some protective enzymes in Brassica chinensis seedlings to Pb2+,
      Cd2+ and Cr6+ stresses].
AB  - Seedlings of Brassica chinensis were cultured in 1/2 Hoagland solution for seven
      days before they were treated with Pb2+, Cd2+ and Cr6+. The activities of their
      superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) responded to the
      increasing concentrations of the metals, and the responsive characters varied
      with different metals and different durations of metal treatments. CAT activity
      decreased with the increase of metal concentrations, and the order of its
      sensitivity to the three metals was Cd2+ > Cr6+ > Pb2+. SOD activity followed a
      rise-fall pattern along metal concentration gradient, but its sensitivity
      decreased with the duration of metal treatment. There was an obvious difference
      in POD activity to different metals, only when the treatment was proceeded for a
      period of time.

PMID- 12222066
TI  - [Generators of walking movements in humans: spinal mechanisms of their
      activation].
AB  - The paper is focused on spinal generation of walking movements in patients
      afflicted with loss of supraspinal control consequent to back trauma. The author
      cites literature on methods of initiation of walking movements with
      pharmacological and proprioceptive stimulation. On his own experimental
      investigations with epidural electrical stimulation of the spinal marrow dorsal
      surface he proves existence of walking generators in the human. There is evidence
      that the walking pattern in extensors is formed through amplitude modulation of
      monosynaptic reflexes, whereas in flexors it is established through switching of
      the reflex paths from the monosynaptic reflex to the polysynaptic neuron network.
      Investigations of the functional deafferentation of lower extremities showed that
      walking movements as a result of epidural stimulation are intraspinal by origin
      and adjusted by way of peripheral feedback. A hypothetical sequence of activation
      of walking generators through the propriospinal system of dorsolateral and
      ventrilateral funiculi has been put forward.

PMID- 12222067
TI  - [Muscarinic receptors of the neostriatum -- important targets of regulation of
      instrumental movement and posture].
AB  - Chronic experiments with 10 dogs were conducted to study effects of bilateral
      microinjections of the nonselective agonist of the muscarinic receptors
      carbachol, nonselective blocker of the muscarinic receptors scopolamine and
      selective blocker M1 of the muscarinic receptors pyrensepine on the instrumental
      defensive reflex in the neostriatum to sustain a given flexion amplitude and
      posture adjustment. Microinjections of carbachol were found to increase tone and
      stem the phase of the reflex, make posture adjustment more orderly and
      amplitudinous. Repeated microinjections gave the instrumental movement a ramp
      like form. Chronic carbachol microinjections (over several years) resulted in
      akinesis and rigidity in dogs. However, these led to impairment of the diagonal
      pattern of posture adjustment as in pathologic so in normal dogs. These
      developments were partially meliorated by dopamine, scopolamine and pyrensepine
      which sharply increased the phase component of the instrumental movement. These
      findings are interpreted in the light of the concept of two neostriatum efferent
      outputs with opposite effects on respective targets and the muscarinic and
      dopamine receptors as their triggers and blockers. Results of the experiment
      bring to the conclusion that activation or blockage of the muscarinic receptors
      in the neostriatum can modify an existing motor behavior and compensate motor
      pathology in dogs.

PMID- 12222068
TI  - [Structural-metabolic plasticity of mammalian skeletal muscles in hypokinesis and
      weightlessness].
AB  - Under review are investigations of the contractile structure of skeletal muscles
      of humans and animals (rats and primates) following space flight, long-term
      hypokinesia, immersion (human subjects) and head-down suspension (rats). Close
      consideration is given to experimental testing of hypotheses concerning neuronal,
      humoral and cell processes leading to atrophy. Described are consistencies and
      mechanisms of changes in the myosin phenotype and electromechanic coupling in
      muscular fibers as well as their capillarization and energy potential.

PMID- 12222069
TI  - [Coefficient of oxygen diffusion in fibers of the skeletal muscles].
AB  - The effective coefficient of oxygen diffusion in muscle fibers (DO2eff)
      calculated from measured values of O2 critical pressure, O2 intake and fiber
      diameter in different skeletal muscles in vertebrates turned to be equal to (0.9
      1.8) x 10(-6) cm2/s, which is 11 to 33 times lower than O2 in water. In mature
      animals, DO2eff reaches this value after the fiber diameter has grown to the
      maximum. In embryos and developing species with thinner myofibers DO2eff is
      significantly lower. Variations in oxidative metabolism in the fiber do not
      change DO2eff. Temperature drop in the fiber by 10 degrees C reduces DO2eff by
      approximately 30%. Modeling of the oxygen regimes in skeletal muscles with low
      DO2eff demonstrated that increase of the size of the O2-rich interstitium from 9
      up to 25% reduces the diffusive resistance to O2 on the way from the capillary to
      mitochondria by approximately 20% (1); in combined muscles hypoxic areas may
      appear in the center of fibers with a high O2 demand, particularly when diameters
      of these fibers are comparatively large (2); the volumetric blood flow in the
      muscle can be infinitely large and O2 pressure in veins can remain high (the so
      called functional shunting).

PMID- 12222070
TI  - [Effects of gravitational unloading on blood supply of working muscles].
AB  - Exposure to the conditions of simulated gravitational unloading (head down
      tilting, dry immersion) produces a material effect on blood supply of working
      muscles in humans that may depend on type of work (local or global) and posture
      (vertical or horizontal). Peak blood flow in the calf after exposure to HDT and
      dry immersion reduces by 7 to 20% and the post-contraction hyperemia (PCH)
      following a standard work of the calf extensors noticeably increases. In contrast
      to PCH, blood flow during natural locomotion diminishes as a result of simulated
      gravitational unloading. Standard bicycling by sitting and supine human subjects
      moderates and exaggerates the post-work hyperemia, respectively. Consideration is
      given to possible causes of these effects.

PMID- 12222071
TI  - Effects of simulated microgravity on leg venous compliance in orthostatic
      intolerance.

PMID- 12222072
TI  - [Characteristics of the post-traumatic reparative process in the M. soleus of
      rats subjected to extended suspension].
AB  - Histological methods were applied to study the course of post-traumatic
      reparation of m. soleus in rats subjected to a 30-d head-down suspension. Muscles
      in unconscious animals were traumatized on day 15 of suspension by crushing a
      small part with the artery clamp. Deprivation of the support loading led to
      development of muscle atrophy so that mass of the muscle in sacrificed animals
      was by 53.7% less as compared to the controls. It was shown that reparation
      phases in the atrophied muscles were not upset; however, the absolute size of the
      reparation field was significantly less when compared with the control animals.
      whereas its relative size was similar to the control. This kind of phenomenon is
      ascribed to the prevalence of catabolic processes in compromised muscles and
      consequent decline in production of myoblasts and the connective tissue which
      forms the frame of the reparative field.

PMID- 12222073
TI  - [Healing fibular bone fracture in rats during extended suspension ].
AB  - Healing of peroneal bone fracture was studied histologically and
      histomorphologically in rats exposed to a 30-d tail-suspension. To fracture
      bones, anesthetized rats were operated on day 15 of suspension. Hind limb
      deprivation of the support loading for a period of 30 days minimizes healing
      processes in fractured peroneal bones as was evidenced by undersized callus and
      lowered strength of bone consolidation. Mass-metric and histomorphometric
      investigations showed that, as compared with the control, on day 15 of
      regeneration the callous mass and volume in the suspended rats were by 34% and
      35% less, respectively; the newly formed spongy bone, the fibrous-cartilaginous
      tissue and the cartilage were by 44%, 70% and 86% smaller in size, respectively.
      Nonetheless, healing dynamics in the suspended rats was not disturbed and the
      calluses were on the same phase of development as in the control, which is
      attested by similarity of the histological picture. Based on the comparative
      retrospective analysis of fracture healing in rats in 15- and 30-d experiments,
      the extended (30-d) suspension did not further impede the post-traumatic bone
      regeneration. It is suggested that minimization of bone fracture healing during
      the 15-d suspension was conditioned not only by inhibition of the growth hormone
      production but also by an acute stress reaction in the early period of
      adaptation.

PMID- 12222074
TI  - [New possibilities of the use of space technologies in the treatment of children
      with injuries of the central nervous system].
AB  - The computerized stabilography was used to study the role of the visual analyzer
      (VA) in vertical posture acquisition and specifics of posture implementation by
      patients with craniocerebral injury (CCI) wearing suit Adele for dynamic
      proprioception correction (SDPC). Results of the investigation revealed a
      decreased vertical stability (VS) of CCI patients and a greater reliance on VA,
      which may be a compensatory instrument. Following the SDPC course, vertical
      stability was improved and the VA role in posture acquisition normalized
      suggesting alteration of the interanalyzer interaction in CCI patients owing to
      the treatment of proprioception impulsation.

PMID- 12222075
TI  - [A system for biomaterial handling and sample pretreatment in conditions of
      weightlessness].
AB  - To perform laboratory biochemical, immunologic and microbiological analyses and
      special pretreatment and stabilization of biosamples immediately on the space
      station, system Plasma-03 was designed and manufactured and associated procedure
      for sample collection and pretreatment was developed. Main elements of the system
      are a refrigerator/thermostat, centrifuge and returnable container, and a set of
      accessories and expendables. The system meets the requirements to the equipment
      to be employed in crew health monitoring and biochemical experiments on board the
      International space station.

PMID- 12222076
TI  - [Development of multidimensional scaling methods in biomedical research].
AB  - Analyzed were different approaches to the construction of multidimensional scales
      to be used in comparison of experimental biomedical data. Pinpointed were weak
      points of the existing models. Multidimensional scaling algorithms can be adapted
      by substituting the notion of "measure of nearness" between characteristics
      studied with the dispersion analysis which is the most valuable part of the
      multidimensional methods--orthogonal scaling (from one up to three scales).
      Integral criterion D2 1,2 allows evaluation of both individual and typological
      reactions of the body systems to various factors.

PMID- 12222077
TI  - A brief history of childhood-onset bipolar disorder through 1980.
AB  - The concept of bipolar disorder in children has its roots in ancient medicine.
      This article reviews the history of bipolar disorder, beginning from its early
      history in ancient Greece through 1980, when diagnostic criteria for children
      were being considered. The acceptance of bipolar disorder in children was highly
      controversial after the first criteria were developed by Anthony and Scott in
      1960. The concept was rejuvenated when Robert DeLong investigated the use of
      lithium in children with symptoms of mania. In the late 1970s and early 1980s,
      diagnostic criteria began to define the major criteria for bipolar disorder in
      children.

PMID- 12222078
TI  - Bipolar disorder in adolescence and young adulthood.
AB  - The purpose of this article is to present findings from the Oregon Adolescent
      Depression Project regarding full-syndrome and subthreshold bipolar disorder (BD)
      in adolescence and young adulthood. BD first incidence peaked around age 14
      years. Adolescent BD showed significant continuity across developmental periods
      and was associated with adverse outcomes during young adulthood. Subthreshold BD
      results provide partial support for a bipolar spectrum.

PMID- 12222079
TI  - Depression among youth in primary care models for delivering mental health
      services.
AB  - This article emphasizes the promise of efforts to improve care for depression
      within the primary care setting. These efforts, however face a number of
      potential obstacles. We have reviewed the literature on the detection and
      treatment of depression among youth in primary care settings and argue that
      primary care offers underutilized potential for reaching out to youth and
      improving access to high-quality care for depression. Much work remains to be
      done before this potential can be realized. The recommendations below highlight
      crucial directions for future research and clinical efforts: 1. Traditional
      primary care practices offer an opportunity to identify and reach youth who need
      care for depression. To reach youth who do not present in typical primary care
      settings, outreach is needed to emergency services, urgent care, and obstetric
      gynecologic settings. The increased emphasis on developing school-based and
      school-linked health centers may also prove helpful for increasing the number of
      youth who are seen in primary care because there centers bring the services to a
      setting that is easily accessible to most youth. 2. Strategies for improving
      detection of depression in primary care settings must be developed and tested.
      Given the constraints of primary care visits, these strategies must be relatively
      brief and not require extensive primary care provider time. Use of nonphysicians
      such as practice assistants, nursing staff or associated mental health workers
      will be needed to support physician efforts. Furthermore, although brief self
      report instruments may be useful in identifying a broad group of youth who may
      benefit from care, available instruments are likely to lead to over
      identification and will require additional screening and triage of youth to
      appropriate services. Some identified youth may be require or want care; others
      may require further evaluation; others can be treated through primary care
      resources; and others will have complex conditions that require specialty
      consultation or referral. 3. Low rates of detection and evidence-based treatment
      for depression in primary care settings underscore the urgent need to
      understanding the barriers to care within primary care settings and to develop
      interventions that reduce potential barriers and improve access to high-quality
      care. 4. Detection efforts within primary care settings are likely to yield a
      somewhat different population than the population of youth identified in
      specialty mental health clinics or schools. Notable, physical health problems are
      likely to be more common in primary care populations. The limited extent data
      also suggest that, as in most non-primary care samples of depressed youth, youth
      with depression seen in primary care settings are likely to present with a number
      of comorbid mental health conditions. Thus, there is a need to test extent
      treatments within primary care settings, and adaptation may be required to meet
      the needs of youth seen through primary care. 5. Motivation for treatment is
      likely to be lower for youth identified through primary care than for those seen
      in specialty care, particularly when youth have not identified themselves as
      requiring treatment. Strategies need to be developed and tested to enhance
      motivation and to target treatment efforts at those youth who are most likely to
      benefit from services. 6. The confidential nature of the patient-provider
      relationship, particularly in primary care settings where youth have sought care
      for sensitive issues (e.g., pregnancy, birth control), underscores the need to
      develop effective strategies for working with families and mobilizing parents to
      support treatment and recovery. In primary care settings, parents may be less
      likely to be aware of youth problems, and youth may be reluctant to disclose
      difficulties to their parent. 7. Research is needed to identify service-delivery
      strategies tht are practical in real-world settings and are associated with
      improved quality of care and outcomes in children and adolescents treated for
      depression in primary care settings. 8. Collaborative models of service delivery
      seem to be promising. These models build on the strengths of primary care
      settings and relationships and suport primary care providers with resources that
      enables them to expand with diagnostic and treatment targets to include
      depression and other mental health problems. The recent and ongoing studies
      reviewed in this articles provide some examples of these models. Future research
      is needed to clarify the effectiveness, costs,and benefits of this approach.

PMID- 12222080
TI  - Etiology and genetics of early-onset mood disorders.
AB  - Most studies dealing with the familiality and genetics of mood disorders have
      been limited to adults, but several studies suggest that there is continuity
      between childhood- and adolescence-onset depression and mania and adult illness.
      More direct estimates of the heritability of depressive symptoms or episodes in
      children and adolescents indicate that the genetic contributions may be greater
      than 50%. A number of functional and structural imaging studies have identified
      particular circuitry as being involved in the generation of emotion and mood
      disorders. Imaging studies of twins have suggested that regional brain volume and
      characteristics of brain shape are heritable. A potentially important new avenue
      of research will be the correlation of the genetics of brain structure or
      function with the genetics of mood disorders. Preliminary studies of adolescent
      and young adult twins suggest a significant correspondence between the genetic
      contributions to some regional brain volumes and early-onset mood disorders.

PMID- 12222081
TI  - Affective neuroscience and the study of normal and abnormal emotion regulation.
AB  - Affective neuroscience allows investigators to study the biologic basis of
      psychologic phenomena such as emotion and mood. Understanding the components of
      emotion, valence, and arousal and their physiologic correlates is the starting
      point for studies that quantify emotional and physiologic reactions. This
      information could provide insight into the biologic foundations of numerous
      psychiatric conditions. Understanding the normal development of emotions and
      regulation of emotion will provide new avenues of research into the complex
      problem of severe mood disorders.

PMID- 12222082
TI  - Children of parents with bipolar disorder. A population at high risk for major
      affective disorders.
AB  - Children of parents who suffer from bipolar disorder are largely ignored by
      psychiatric services despite the fact that they constitute a population at very
      high risk for major depression and bipolar disorder in adulthood and a wide
      variety of disorders in childhood and adolescence. Major depression and bipolar
      disorder are chronic, recurrent disorders that seriously impair psychosocial
      functioning across the life-span. Evidence suggests that in this population
      bipolar disorder is preceded by externalizing disorders in childhood in many
      cases, and by depression in some cases. While heredity provides the vulnerability
      for the development of these characteristics, being raised by parents who model
      inappropriate coping skills, create a stressful family environment, and provide
      inadequate support and structure, contribute to consolidating these
      characteristics.

PMID- 12222083
TI  - Somatic treatment for depressive illnesses in children and adolescents.
AB  - Numerous somatic interventions have been studied as potential treatments of
      depressive disorders in children and adolescents. These include antidepressant
      medications, light therapy, electro-convulsive therapy, and alternative
      therapies. The available evidence suggests that several somatic interventions
      hold promise as potentially safe and effective treatments for depressed youth;
      however, there is still much to be learned about these interventions. This
      article reviews what is known and what needs to be learned about the somatic
      treatment of pediatric depression.

PMID- 12222084
TI  - Nonsomatic treatment of depression.
AB  - There is solid evidence that active and goal-oriented cognitive-behavioral or
      relationship-focused therapies are generally superior to more generic therapies
      or to no treatment for clinically diagnosed and for undiagnosed but symptomatic
      youths. Between 50% to 87% of diagnosed youths who received a targeted treatment
      had recovered from their depressive episodes, in comparison to 21% to 75% of
      those who received some other generic therapy and 5% to 48% of wait-listed
      youths. The cognitive behavioral and relationship-oriented interventions that
      were tested tended to be even more successful in reducing depressive symptoms in
      school-based samples, possibly because the participants in the school-based
      studies may have been less disturbed than the clinically diagnosed cases.
      Although the targeted treatments generally yielded better results than the
      comparison conditions, the targeted interventions seem to be similarly successful
      in ameliorating depression. Determining which psychosocial therapy works best for
      a given depressed youngster remains problematic. As noted in recent reviews
      [30,46,47], little attention has been devoted to which interventions, or parts of
      an intervention, are likely to be effective with children with various
      characteristics. This issue acquires added importance because in some diagnosed
      samples half or more of the treated participants were still in a depressive
      episode at the end of the trial. Likewise, in intervention studies involving
      symptomatic, school-based youngsters, not all children improved, and gains were
      not uniform across domains of functioning (e.g., severity of depression, self
      esteem, global functioning). Possibly, for some of the nonresponders, the
      participant's characteristics and relevant problems and the target interventions
      were mismatched. For example, a depressed youth with a long history of highly
      dysfunctional relationships may not respond optimally to a therapy focusing on
      negative cognitions; alternatively, interpersonal therapy may not be the most
      effective treatment for a youth dispositionally inclined to negative ruminations
      about the self and for whom relationship issues are not the most relevant.
      Empiric information about the relationship between the underlying processes
      presumed to account for the onset and maintenance of depression and recovery from
      depression is limited. Few studies of youths provide direct evidence tht
      cognitive-behavioral interventions change depressogenic cognitions, explanatory
      style, and pleasent events, among others, that relationship-focused approaches
      predictably alter relevant interpersonal processes, or that improvements in these
      domains relate to overall depression outcomes. Admittedly, the designs of extent
      studies typically preclude conclusions about the relationship between changes in
      target processes and improvement in depression or about treatment specificity.
      More compelling evidence linking changes in targeted mechanisms to decreases in
      depressive symptoms comes from a controlled prevention trial involving 10- to 13
      year-olds that used cognitive restructuring, social problem-solving, or a
      combination intervention [48]. According to the results, changes in explanatory
      style were related to decreased depression and accounted for a significant
      portion of the variance in changes in depression even after controlling for
      treatment assignment. Further research along such lines may help identify which
      treatment may be most effective for a patient with a given set of
      characteristics. To improve patients' response rates to specific treatments, it
      also would be helpful to understand better the impact of other attributes, such
      as psychiatric comorbidity, and contextual factors, such as parental
      psychopathology, on the process of recovery. With few exceptions [25], however,
      such variable have not yet received sufficient attention. Recent reviews also
      have noted that researchers typically use multi-component interventions in
      treatmenttrials [46,47]. This design an make it difficult to identify which
      particular treatment ingredient is instrumental in general or among children with
      specific characteristics. Thus, empiric initiatives also are needed to determine
      the active ingredients of experimental therapies for depressed youths. Existing
      models include component-analysis or dismantling studies of multi-faceted
      treatments for depressed adults [49,50]. Once the improtant prognostic factors
      and active ingredients of therapies have been identified, it will be possible to
      conduct studies in which children are either "matched" or "mismatched" to
      treatment conditions. To achieve meaningful results and to enroll sufficient
      numbers of youths, collaborative, multisite efforts may be required. What
      treatment should be endorsed for depressed youths from the perspective of health
      services policy? When the criteria of the Task Force on Promotion and
      Dissemination of Psychological Procedures [1] are applied broadly, both cognitive
      behavioral and interpersonally oriented therapies can be deemed efficacious. Both
      approaches have been tested in different samples by two independent teams and
      thus may be regarded as well-established treatments for depression in youths. If
      the criteria are applied more stringently, so that exactly the same intervention
      is tested independently by two or more research teams, interpersonal therapy and
      cognitive behavioral therapy would be regarded as "probably efficacious". Namely,
      the two trials of interpersonal therapy apparently used somewhat different
      versions because of cultural differences in the samples. The complete CWD course
      has been tested and the results replicated only by its originators [20,21]. Other
      trials of cognitive behavioral therapy entail various different study-specific
      approaches and consequently cannot serve as replications [46,47]. A next step in
      psychotherapy research might therefore involve further independent replication of
      standardized, previously studies therapies. In their landmark meta-analytic study
      of the efficacy of psychotherapy for adults, Smith et al [51] concluded that all
      psychotherapies are about equally beneficial and that distinctions among them,
      although "cherished by those who draw them ... make no important differences: (p.
      186). Likewise, the various psychotherapies for depresed youths that have been
      examined seem to produce similar rates of improvement ( or alternatively, similar
      limits in efficacy) across the tested therapies and the scant data regarding
      meaningful prognostic factors might indicate that at present it does not matter
      what type of brief, goal-oriented nonsomatic therapy is used to treat pediatric
      depression. Alternatively, one might conclude that patients who fail to respond
      may have been mismatched to a therapy that was not focused on their primary
      depression-related deficits. Thus, clinicians who treat depressed children and
      adolescents are faced with substantial challenges, and to date, results of
      controlled psychotherapy trials with depressed youths offer limited guidance
      regarding choice of treatment. Nonetheless, some general guidelines can be culled
      from the available data. For example, interventions of elements of therapies that
      are structured and directed towards cognitive, behavioral or relationship issues
      show promise for the treatment of juvenile depression. It also appears that group
      interventions may be used as profitably as the more traditional individual
      therapy formats. And although parental participation in empiric treatment trials
      of pediatric depression has been limited to either separate parent groups as an
      adjunct [20,21 or family therapy [7], it can be argued that for various practical
      and clinical reasons [30] direct involvement of parents may be a wise choice.
      Parents may be critical to the success of interventions with depressed children
      and should be regarded as potential important agents of change.

PMID- 12222085
TI  - Somatic treatment of bipolar disorder in children and adolescents.
AB  - The currently available data from randomized, controlled trials and a
      considerable amount of open clinical data suggest that adolescent-onset bipolar
      disorder probably responds to the same agents as adult-onset bipolar disorder.
      Research examining psychopharmacologic treatment approaches in the early-onset
      bipolar disorder is limited, however. Methodologic problems include small sample
      sizes, lack of comparison groups, retrospective designs, and lack of standardized
      measures. In addition, sometimes no clear differentiation is made between mania
      and bipolar disorder, the latter term being used broadly in the literature. Often
      the studies show that symptoms improve because of treatment, but the functioning
      of the patients does not improve significantly. More research is clearly needed
      in all aspects of this disorder but especially in examining the efficacy of
      various types of treatment, its longitudinal course, and diagnostic issues. The
      indications for, and the overall duration of, long-term maintenance therapy need
      further study. Many adolescents and children with bipolar disorder do not respond
      to any of the first-line pharmacologic treatments; therefore, studies with novel
      agents should be extended to patients in this age range. Furthermore, physicians
      will probably continue to use combination therapies when confronted by either
      lack of efficacy or delayed onset of efficacy with a single agent. Thus, such
      resultant drug-drug interactions also should also be systematically studied [97].

PMID- 12222086
TI  - Course and outcome of child and adolescent major depressive disorder.
AB  - Major depressive disorder (MDD) is a familial recurrent illness that
      significantly interferes with the child's normal development and is associated
      with increased risk for suicidal behaviors and psychiatric and psychosocial
      morbidity. Although most children and adolescents recover from their first
      depressive episode, 30-70%, in particular those with familial history of MDD,
      comorbid psychiatric disorders, dysthymia, subsyndromal symptoms of depression,
      anxiety, negative cognitive style, and exposure to negative life events (e.g.,
      family conflicts and abuse) will experience one or more depressive recurrences
      during their childhood, adolescence, and adulthood. Depressed youth who present
      with psychosis, psychomotor retardation, pharmacological induced hypomania/mania,
      and/or family history of bipolar disorder are at high risk to develop bipolar
      disorder.

PMID- 12222087
TI  - Suicide in mood disordered children and adolescents.
AB  - This article reviews the risk factors for fatal and nonfatal suicidal behavior in
      children and adolescents. Numerous empirical studies suggest that mood disorders
      are among the most important risk factors for youth suicidal behavior. In
      addition, other psychosocial factors increase risk for youth suicidal behavior
      independent of mood disorders. Prevention strategies for suicidal behavior should
      incorporate methods to identify children and adolescents who suffer from major
      depressive, dysthymic, and bipolar disorders. Such strategies should identify
      children and adolescents who have a history of suicidal ideation and/or suicide
      attempts.

PMID- 12222088
TI  - Aggression and violence in mood disorders.
AB  - As a common component of mood disorders, aggression can have many adverse effects
      on the child's or adolescent's life, including disrupting school performance and
      causing personal rejection by family, peers, and teachers. The problems of
      children and adolescents with mood disorders are compounded by comorbid
      aggressiveness. Without effective treatment for both problems, many of these
      aggressive, depressed children and adolescents go on to experience multiple
      failures in life leading to disturbances in character and the inability to
      establish fulfilling interpersonal relationships. This article is intended to
      heighten clinician awareness of the complex relationship between mood disorders
      and aggression.

PMID- 12222089
TI  - What is new in bipolar disorder and major depressive disorder in children and
      adolescents.

PMID- 12222090
TI  - Information retrieval on the Internet: a guide for dental practitioners.
AB  - The Internet is not designed for efficient information retrieval. Searchers
      experience difficulties when trying to find information quickly. Once they find
      the information, they often cannot assess the validity of the information or its
      origin. Various Internet search engines and information retrieval systems try to
      facilitate this process to make the searching more efficient. Searchers use these
      services, which are usually free, to satisfy their information needs. Knowing
      when to use which search engine and how to use it is crucial to finding the right
      information in a timely fashion.

PMID- 12222091
TI  - Dental practice websites: creating a Web presence.
AB  - Web technology provides an opportunity for dentists to showcase their practice
      philosophy, quality of care, office setting, and staff in a creative manner.
      Having a Website provides a practice with innovative and cost-effective
      communications and marketing tools for current and potential patients who use the
      Internet. The main benefits of using a Website to promote one's practice are:
      Making office time more productive, tasks more timely, follow-up less necessary
      Engaging patients in an interactive and visual learning process Providing online
      forms and procedure examples for patients Projecting a competent and current
      image Tracking the usage of Web pages. Several options are available when
      considering the development of a Website. These options range in cost based on
      customization of the site and ongoing support services, such as site updates,
      technical assistance, and Web usage statistics. In most cases, Websites are less
      expensive than advertising in the phone book. Options in creating a Website
      include building one's own, employing a company that offers Website templates,
      and employing a company that offers customized sites. These development options
      and benefits will continue to grow as individuals access the Web and more
      information and sites become available.

PMID- 12222092
TI  - Application service providers in dentistry.
AB  - ASP practice management systems are a new and potentially useful service for the
      dental profession. ASP systems have the potential to reduce the time, effort, and
      expense required to maintain computer-based practice management functions. ASP
      systems can deliver a rich array of functions at a distance, eliminate concerns
      about upgrades, back-ups, and server hardware, and make management of client
      workstations easier. The ASP industry is young, however, and its companies and
      products will be in constant flux. Practitioners should exercise great caution in
      selecting an ASP system. If the ASP model proves viable in dentistry over the
      long term, we can expect to see a growing number of services being delivered over
      the Internet. Many ASPs exist already that serve many needs of small businesses,
      such as accounting, personnel management, and supply ordering. Application
      service provider systems also have the potential to improve communication between
      dental care providers. The ease of exchanging selected patient information
      between providers may result in more patient-related information exchange than is
      currently the case. The quality of dental care can only benefit.

PMID- 12222093
TI  - The virtual articulator in dentistry: concept and development.
AB  - Virtual Reality (VR) technology is one of the most important innovations for
      research, development, and industrial production. In dentistry, VR technology
      will be useful in providing better education through simulation and in enhancing
      working procedures that are conventionally limited, e.g., the mechanical
      articulator. It is the purpose of this article to present concepts and strategies
      for a future replacement of the mechanical articulator by a virtual one.

PMID- 12222094
TI  - Orthodontic referrals via TeleDent Southwest.
AB  - The information presented in this article must be interpreted with caution.
      Ideally the trial should have lasted longer because five of the seven
      participating dentists said they felt constrained from taking in more cases
      because access to TeleDent advice would cease before completion of all but the
      shortest of treatments. Second, the number of practitioners recruited into the
      trial was small, and the dentists chosen were highly selected. Third, almost all
      the data are based on the opinions of the participating dentists, and for three
      of the dentists the number of cases on which those opinions were based was small.
      Finally, it must be remembered that all United Kingdom NHS dentists are busy and
      work on a highly structured "time of service" payment system. Although the costs
      of hardware, software, line rental, and training were borne by the TeleDent
      project, there was no financial compensation for the time spent by dentists
      capturing images of their patient records and putting together the whiteboard and
      transmitting the information. There was a significant financial disincentive for
      using the system. Ideally, a long-term prospective randomized study of the effect
      of teledentistry advice on outcome of orthodontic treatment provided by general
      dental practitioners should be undertaken. The data collected in the current
      study supported the dentists' opinions that TeleDent SW enabled them to offer a
      better service for their patients and use specialist services more appropriately.

PMID- 12222095
TI  - Clinical decision-making using computers: opportunities and limitations.
AB  - This paper deals with the use of information technology in order to make clinical
      decisions in dentistry. Since there is a large number of available systems and
      ongoing projects using computers, we first identify and describe major streams,
      as well as singular specialties. We underline the need for standards for data
      format and exchange in addition to the ability of different systems to
      communicate with each other. We conclude with a five-step recommendation to
      transform a dental office into digital and how to implement a computer-aided
      clinical decision support system, which provides action-oriented support in order
      to reduce the likelihood of human error during dental treatment.

PMID- 12222096
TI  - Handheld computing in dentistry.
AB  - Handheld computer sales are increasing rapidly in the United States and
      worldwide. The convenience and communication features will continue to improve
      and become commonplace in our lives. Using a handheld computer in the dental
      environment is efficient and potentially aids the dentist in delivering a higher
      standard of care to patients.

PMID- 12222097
TI  - The Health Insurance Portability and Accountability Act: implications for the
      dental profession.
AB  - HIPAA is generating long-awaited change in the health care world. Administrative,
      operational, and technical solutions are being created in response to the
      requirements of HIPAA. The current rules emphasize that the regulations'
      provisions are scalable and allow all entities, whenever possible, to determine
      how extensively they will address certain issues. The larger the organization,
      the more complex the HIPAA strategy must be. Implementation in a small dental
      practice requires a simple strategy compared to that of a health care plan or
      clearinghouse. It still takes time and resources for a dental practice to
      accommodate the numerous HIPAA requirements, however. Although a dentist may find
      the rules at HHS Web site or other Internet sites, he or she may wish to rely on
      vendors, consultants, and the guidance of the ADA and other dental organizations
      to help implement them. The dentist also should keep in mind that HIPAA
      compliance is an evolutionary process; future modifications are necessary. As a
      result, some of the information contained in this material may not be accurate by
      the time this issue in printed. Dentists always should consult sources such as
      the ADA or HHS Web site to procure current HIPAA information.

PMID- 12222098
TI  - Use and implication of the DICOM standard in dentistry.
AB  - DICOM is an international imaging standard that was developed for medicine and
      has been extended to support dentistry among other professions. This standard can
      provide the basis of interoperability for digital system outputs, providing image
      portability and reducing the danger of obsolescence rendering valuable diagnostic
      information impossible to display. This paper presents a brief overview of the
      origins and components of the DICOM standard and reports an ongoing initiative to
      promote interoperability within the DICOM as the industry standard for digital
      imaging in dentistry.

PMID- 12222099
TI  - Interactive multimedia patient simulations in dental and continuing dental
      education.
AB  - Transfer of knowledge from the basic biopsychosocial sciences to patient care is
      a major task for dental students during their education. Computer-based
      interactive patient simulations can help students affect this transfer because
      simulations allow students to develop and practice problem solving and decision
      making skills interactively within the context of patient problems. A program for
      authoring computer-based interactive simulations is described. Patient
      simulations can effectively integrate basic science relevance, preparation for
      clinical problem solving, teaching new clinical content and several other
      necessary elements into curriculum infrastructure. Case simulations also can
      contribute to evolving educational standards set out by accrediting bodies.

PMID- 12222100
TI  - Continuing dental education on the World Wide Web.
AB  - Continuing dental education (CDE) courses delivered on the World Wide Web (Web
      CDE) offer numerous advantages over traditional CDE; however, two major issues-
      location of suitable courses and course quality--need resolution. Locating high
      quality courses is difficult due to the lack of the standardized metadata that
      allows search engines to match courses to practitioners' needs. Web directories
      created by professional organizations are beginning to show promise, but require
      further development. Search engines and Web directories are discussed and
      improvements currently underway summarized. Course quality remains a highly
      significant concern. A national effort to create Web CDE course quality standards
      is underway that includes proposed standards. These proposed standards are
      summarized and used to comment on the current state of Web CDE courses. Examples
      are given when possible. Three emerging Web CDE technologies and a look to the
      future of Web CDE are discussed.

PMID- 12222102
TI  - Dental informatics.

PMID- 12222101
TI  - What data integration means to the practicing dentist.
AB  - Practitioners all have been confronted with unscheduled, emergency care patients.
      Their immediate concern is usually pain relief, and they may not always provide
      accurate or complete information about their health history. They may be
      distracted by pain, lack the understanding of their health to answer
      appropriately, or by intention or oversight omit or provide faulty information.
      Faced with omissions and inconsistencies, practitioners make an extra effort to
      explore their health history and, if indicated, consult their physician. Although
      the information that is developed creates a more complete and more accurate
      picture of a patient's health, there is always a small risk of omission or
      misrepresentation of a significant item. Although chances are that this
      misrepresentation will have little impact on how the practitioner handles the
      case, there is that one case in a thousand that can ruin one's day and possibly
      one's practice.

PMID- 12222103
TI  - Trial lawyers vs tort reformers.

PMID- 12222104
TI  - The use of ACE inhibitors in the treatment of heart failure in Kentucky Medicare
      beneficiaries: a quality improvement project.
AB  - Heart failure (HF) is a highly prevalent and frequently fatal condition. During
      1998, 10,815 Medicare beneficiaries in Kentucky were diagnosed as having HF;
      14,777 beneficiaries were hospitalized for the condition, and 696 Medicare
      beneficiaries died with HF as the primary diagnosis. Proper diagnosis and
      subsequent treatment with angiotensin converting enzyme (ACE) inhibitors improve
      functional status, quality of life, and survival among HF patients. Health Care
      Excel, Incorporated (HCE), the Medicare Quality Improvement Organization for
      Kentucky, collaborated with a select group of Kentucky hospitals to conduct an HF
      quality improvement project. The improved pharmacotherapy by these hospitals is
      presented and discussed. The use of ACE inhibitors improved from 54.1% to 66.0%
      and the use of either ACE inhibitors or angiotensin II receptor blockers (ARBs)
      to 72.1%.

PMID- 12222105
TI  - Privacy.

PMID- 12222106
TI  - William Wesley Anderson, MD [1866-1946].

PMID- 12222107
TI  - Characteristics and capabilities of the hyperspectral imaging microscope.

PMID- 12222108
TI  - Are you conscious, and can you prove it?

PMID- 12222109
TI  - Cloning.

PMID- 12222110
TI  - The evolution of custom microarray manufacture.

PMID- 12222111
TI  - Publish and perish.

PMID- 12222112
TI  - Progress in the analysis of heart-rate variability.

PMID- 12222113
TI  - Neurovisceral integration in cardiac and emotional regulation.

PMID- 12222114
TI  - Examining changes in HRV in response to varying ambient temperature.

PMID- 12222115
TI  - Validity concerns of common heart-rate variability indices.

PMID- 12222116
TI  - Estimating respiratory frequency from autoregressive spectral analysis of heart
      period.

PMID- 12222117
TI  - Time-frequency parameters of heart-rate variability.

PMID- 12222118
TI  - The effects of coronary occlusion location on the RR signal.

PMID- 12222120
TI  - Dimensional analysis of HRV in hypertrophic cardiomyopathy patients.

PMID- 12222119
TI  - The effects of controlled smoking on heart period variability.

PMID- 12222121
TI  - Bullseye display of cerebral cortical blood flow.

PMID- 12222122
TI  - Investigating elastic properties of soft biological tissues.

PMID- 12222124
TI  - [The endoscopic approach to isolated sphenoid sinus disease].
AB  - We reviewed the records of 38 patients aged 16 to 76 years with isolated sphenoid
      sinus disease who were treated by intranasal endoscopic sphenoidotomy at our
      hospital during the period 1992-1997. Diagnosis was made on the basis of history
      rigid nasal endoscopy and computed tomography (CT) scan of the sinuses. Headache
      was the main symptom in 29 (76%) patients. Other complaints were rhinitis, cough,
      nasal obstruction and nasal bleeding. Sphenoidotomy was performed endoscopically,
      directly through the area of the natural ostium. Acute or chronic sinusitis was
      found in 57% of the patients, cysts in 13%, polyps in 10%, mucocele in 8%, and
      fungal infection, pituitary adenoma, inverted papilloma and adenocarcinoma, in 3%
      each. Surgical results were excellent. The endoscopic approach proved to be both
      safe and effective. CONCLUSION: Sphenoid sinus disease is mostly inflammatory in
      origin. The endoscopic approach to the sphenoid sinus is currently the most
      appropriate method of surgery for an isolated sphenoid lesion.

PMID- 12222123
TI  - MRI data compression using a 3-D discrete wavelet transform.

PMID- 12222125
TI  - [The frequency and causes of resistant hypertension in primary care practices in
      the community as compared to those in the district advisory clinic for
      hypertension].
AB  - Resistant hypertension is defined as blood pressure that does not drop below 140
      mmHg systolic and/or above 90 mmHg diastolic, despite treatment with three drugs
      in suitable combination and recommended dosage, when one of the drugs is from the
      diuretic group. The prevalence of resistant hypertension, which has been examined
      in relatively few studies, ranges between less than 3% and up to 29%. The
      frequency of these causes has not yet been examined in Israel. The aim of this
      study is to examine the frequency of patients with resistant hypertension and to
      compare the frequency of the different causes for this condition in the primary
      community clinics with those found in the district advisory clinic for
      hypertension. The medical files of all of the patients above the age of 20, in
      five rural primary care clinics in the northern district and in the Advisory
      Clinic for Hypertension, were reviewed to find those patients meeting the
      criteria of resistant hypertension. The patients that were located and met the
      inclusion criteria filled out a questionnaire which included demographic
      characteristics, drug treatment updated to their last visit, and evaluation of
      the various possible causes for the condition. RESULTS: Resistant hypertension
      was found in 10 out of 227 hypertensive patients treated in primary clinics
      (4.4%) and in 21 out of 131 hypertensive patients treated in the Advisory Clinic
      for Hypertension (16%). For 8 of the patients (25.8%) there was a single cause
      for resistant hypertension. For 14 patients (45.2%) there were 2-3 causes and for
      9 patients (29%) there were 4 or more causes. Low treatment compliance was found
      in 7 patients, faulty measuring technique in 3 patients and taking drugs that
      raise blood pressure was found in one patient. Among the accompanying clinical
      conditions, uncontrolled dyslipidemia was found in 15 patients (48.4%),
      uncontrolled diabetes in 11 patients (35.5%) and obesity in 10 patients (32.3%).
      Increased sympathetic activity was found in 6 patients (19.4%) and secondary
      causes were found in 4 patients (12.9%). CONCLUSIONS: The frequency of resistant
      hypertension in primary clinics--4.4%, and in the Advisory Clinic for
      Hypertension--16%, as was found in our study, is identical to that described in
      the literature and derives from the different nature of the patients treated in
      each of them. The fact that in half of the patients 2-3 causes were found for
      resistant hypertension, and in a third of them there were 4 or more causes,
      emphasizes both the complexity of the medical problems of this patient group and
      the need for a comprehensive multi-systematic treatment approach.

PMID- 12222126
TI  - [High rate of sacral fractures in elderly patients presenting pubic rami
      fractures].
AB  - BACKGROUND: Pubic rami fractures are common in the elderly, resulting from low
      energy traumatic falls. The recovery of some of these patients may be
      disproportionately slow. OBJECTIVE: To investigate the characteristics of older
      patients admitted with pubic rami fractures and possible associated pelvic
      fractures. PATIENTS AND METHODS: We have prospectively examined nineteen
      consecutive female patients admitted from the emergency ward with a diagnosis of
      pubic rami fractures, during a one-year period. Patients underwent bone scans and
      pelvis computerized tomography. RESULTS: Six of these patients had associated
      sacral fractures as demonstrated by pelvic CT scan. None of these sacral
      fractures was diagnosed on admission to the emergency ward. CONCLUSION: There is
      a considerable high rate of association of combined pubic and sacral fractures.
      Greater awareness of this clinical condition is required.

PMID- 12222127
TI  - [The epidemiology and clinical features of Legionella pneumonia (LP) in patients
      older than 60 years old who were hospitalized with pneumonia in northern Israel].
AB  - BACKGROUND: Risk factors associated with LP are frequent in patients older than
      60 years old who are hospitalized with pneumonia. The aim of the study was to
      define the incidence, epidemiological and clinical features of LP in this age
      group in Northern Israel. STUDY DESIGN: The study was prospective and conducted
      for one year during the period 1.6.1999-31.5.2000. All patients older than 60
      years who were hospitalized with community-acquired or nosocomial pneumonia were
      tested for legionella infection by the urine antigen test (which identifies
      Legionella pneumophila type I and 14 other Legionella serotype antigens). Data
      was obtained from each patient regarding risk factors and clinical feature of the
      disease. The data of patients with LP was compared on a 1:2 ratio to data
      obtained from a control group of patients with non LP according to age, sex, and
      week of admission. RESULTS: During the study period 202 patients and 38 patients
      were hospitalized with community-acquired or nosocomial pneumonia respectively.
      Overall, 8/240 patients (3.3%) were found to suffer from LP. All patients with LP
      had community-acquired pneumonia with an incidence of 8/202 (4%). Six of the 8
      patients (75%) with LP were hospitalized during June-September. Significant
      clinical findings in patients with LP as compared to those in the control group,
      respectively, were: severity score, history of smoking, mental status alteration,
      respiration rate over 30/minute, respiratory acidosis, hypoxia, and need for
      mechanical ventilation (P < 0.05 in all). All patients with LP were treated with
      macrolides, however the death rate was 50% vs 0% in the control group (p <
      0.001). CONCLUSIONS: In northern Israel, LP is infrequent among patients older
      than 60 years hospitalized with pneumonia. The disease occurs mostly during the
      summer in patients with community acquired pneumonia. Patients with LP had unique
      and more severe clinical features and the death rate was very high inspite of
      appropriate therapy.

PMID- 12222128
TI  - [An outbreak of Campylobacter jejuni enteritis after farm visit in Haifa
      subdistrict].
AB  - We report on an outbreak of Campylobacter jejuni (C. jejuni) gastroenteritis
      among children residing in Haifa subdistrict after a farm visit. This incident
      emphasizes the importance of this issue and our report suggests preventive
      measures to reduce the risk of transmission of enteric pathogens in such
      situations.

PMID- 12222129
TI  - [Salmonella virchow sacroiliitis and bacteremia in a child].
AB  - A 2.5 years old girl was admitted because of high fever and limping that appeared
      two days after she had trauma to her right leg. Bone scan demonstrated increased
      uptake in the right sacroiliac joint, and CT demonstrated right sacroiliitis.
      Salmonella vircow was isolated from the blood culture. The patient recovered
      after a five weeks course of intravenous antibiotics. Salmonella sacroiliitis in
      children is rare, and only seven cases have been reported in the English
      literature in the last 40 years. We reviewed the literature dealing with
      pathophysiology diagnosis therapy and outcome of this infection.

PMID- 12222130
TI  - [Primary well-differentiated papillary mesothelioma of the peritoneum--a rare but
      important differential diagnosis].
AB  - The primary well-differentiated papillary mesothelioma of the peritoneum is a
      rare neoplasm, characterized by an indolent course and good prognosis. We report
      the case of a 55-year-old male, who presented progressive abdominal swelling due
      to ascites. On computerized tomography, the peritoneum was diffusely thickened
      and irregular. Cytologic examination showed a lymphocyte rich ascitic fluid.
      Malignant cells could not be identified. On laparoscopy, numerous nodular lesions
      were observed on the peritoneal surface. A biopsy of the latter showed an unusual
      malignant growth. Using immunohisto-chemistry and electron microscopy, typical
      features of a well-differentiated papillary mesothelioma were recognized. The
      patient underwent tumor debulking. Two years later he is symptom free. This case
      study, much similar to another 38 reported cases in the MEDLINE database,
      illustrates the characteristic features of this rare malignancy that should be
      recognized and distinguished from other, common, more aggressive neoplasms
      involving the peritoneum.

PMID- 12222131
TI  - [An unusual coincidence of thrombotic thrombocytopenic purpura and pernicious
      anemia].
AB  - A 52 year old man was admitted for hospitalization due to dizziness and weakness
      that appeared in the previous 2 weeks. Anemia and thrombocytopenia, as well as
      elevated levels of lactic dehydrogenase, reticulocytosis and schistocytes on
      blood smear, all suggested thrombotic thrombocytopenic purpura. However, B12
      deficiency was also diagnosed. The diagnosis of pernicious anemia was reassured
      by both fundic biopsy and the existence of antiparietal cells antibodies and anti
      intrinsic cells antibodies. A few courses of plasmapheresis along with parenteral
      B12 stabilized his physical condition and he was released with no need for
      further treatment, and only required ambulatory follow-up.

PMID- 12222132
TI  - [Breast reconstruction--where are we heading?].
AB  - Breast reconstruction has become a routine procedure, being performed in a
      growing part of the mastectomy patients' population. Proven improvement in body
      image and in coping with breast cancer encouraged plastic and general surgeons to
      warmly recommend the procedure. The advances in the genetic evaluation of the
      breast cancer population cause an increase in prophylactic surgery and subsequent
      reconstructions. Today, we can offer two types of reconstruction: by using tissue
      expanders or by using autologous tissues from various sources: abdomen, back and
      the gluteal region. The advancement in surgical techniques enable us to offer a
      custom made reconstruction that is performed according to the patient condition
      and desire. We describe our experience in breast reconstruction using Becker
      implant-expanders in 229 patients in the last decade. We detail the organization
      chart of our multidisciplinary breast reconstruction team clinic and we suggest a
      flow chart for the evaluation and planning of breast reconstruction. Custom made
      reconstruction, done in the envelope of a multidisciplinary supporting system is
      the future of this procedure.

PMID- 12222133
TI  - [Malaria in Israel--can severe malaria related morbidity and mortality be
      prevented?].
AB  - Malaria was eradicated in Israel about 50 years ago. Despite this, the number of
      cases of malaria in Israel has been increasing in the past few years due to
      imported malaria from endemic countries. Although malaria is a preventable and
      treatable disease, severe and fatal cases of malaria occur every year. The
      majority of malaria cases occur in travelers who did not take prophylaxis.
      Therefore, there is a tendency to blame them for their severe disease. However,
      malaria morbidity and mortality increases with any delay in diagnosis and
      treatment. Hence, it should be emphasized, that there are three links to this
      chain: the patient who did not take malaria prophylaxis, the physician who failed
      to consider malaria as the diagnosis of a febrile patient who had just returned
      from an endemic area, and finally, the hospitals that usually do not store anti
      malarial medication. Action should therefore be taken on three levels: first and
      most easily remedied--hospitals should have anti-malarial medication available by
      law. Second are the physicians who must be educated with regard to the risk of
      malaria in returning travelers, and methods of diagnosis. Thirdly, efforts must
      continue to increase compliance of malaria prophylaxis among travelers to endemic
      areas.

PMID- 12222134
TI  - [Review of risk factors for breast cancer--what's new?].
AB  - Breast cancer is the most common malignancy in women and constitutes 18% of all
      cancers in women. Female gender, age and country of birth are the strongest
      determinants of disease risk. Family history and mutations in tumor suppressor
      genes BRCA1 and BRCA2 are important correlates of lifetime risk. Genetic
      polymorphisms associated with estrogen synthesis and metabolism are viewed as
      major factors in breast cancer prevalence in specific populations. Atypical
      hyperplasia and ductal/lobular carcinoma in situ although uncommon, are
      considered as pre-malignant conditions as well as markers for invasive breast
      cancer. Lately, increased bone density and high breast tissue density on
      mammogram in postmenopausal women have been reported in association with
      increased risk of breast carcinoma, probably attributable to increased levels of
      endogenous estrogen. Serum estrogen levels are higher in breast cancer cases as
      compared with controls. Current use of oral contraceptives and prolonged, current
      or recent use of postmenopausal hormonal replacement therapy are also considered
      as risk factors for breast cancer. Tamoxifen and raloxifene, selective estrogen
      receptor modulators, were shown to reduce breast cancer risk among high-risk
      women. Various nutrients were evaluated for their possible effect on breast
      cancer risk but further studies are needed. High socioeconomic status is found to
      be associated with increased risk of breast malignancy for as yet unestablished
      reasons. Studying breast cancer risk factors and further research into the
      molecular etiology of the disease will enable early diagnosis and detection of
      high-risk women and ultimately improve prognosis.

PMID- 12222135
TI  - [Diagnostic and resuscitative aspects of pediatric nerve agent intoxication].
AB  - Chemical warfare and the use of nerve agents are still a threat to the civilian
      population in the 21st century. Modern history of chemical warfare began in 1915
      in the battle of Ypres when German troops used chlorine against the French army.
      Since then, the arsenal of such agents has included asphyxiates, burn-causing and
      nerve paralytic agents. Nerve gases are considered the most dangerous of all
      chemical weapons with little known about the treatment of the civilian population
      especially children. Management of the civilian population injured by these
      agents may be a tremendous challenge, especially in children, due to lack of
      previous data regarding pediatric resuscitation. This review emphasizes
      resuscitation issues of the child who suffers from multiple trauma and nerve
      agent poisoning, mainly based on data from reports concerning episodic civilian
      exposure to organophosphates.

PMID- 12222136
TI  - [New trends in the diagnosis and treatment of renal cell carcinoma].
AB  - In the last decade the treatment of renal cell carcinoma (RCC) have changed
      dramatically. Currently, laparoscopic radical nephrectomy, partial nephrectomy in
      the presence of normal contralateral kidney as well as ablative surgery for small
      renal masses, are vivid options for the treatment of localized RCC. For
      metastatic RCC, cytoreductive nephrectomy is the standard of care prior to
      immunotherapy or combined treatment with tumor vaccines. On the horizon are:
      laparoscopic partial nephrectomy for localized disease and allogenic dendritic
      cell--autologous tumor cell hybrid vaccines as a non-toxic tumor vaccine. More
      experimental therapies involving targeting RCC cells using specific markers such
      as G250 are under investigation. In addition, changes in the 1997 TNM
      classification of RCC are anticipated. Retiring--routine adrenalectomy during
      radical nephrectomy and immunotherapy using tumor infiltrating lymphocytes (TIL).

PMID- 12222137
TI  - [Tamoxifen and breast cancer].
AB  - Tamoxifen is a selective estrogen receptor modulator (SERM) with pro- and anti
      estrogenic properties. Currently it is the most widely used agent for first line
      treatment against hormone sensitive metastatic breast cancer and the only
      approved hormonal agent for adjuvant treatment of organ confined breast cancer.
      Furthermore, its uses have been extended for the treatment of intraductal breast
      carcinoma patients. In such settings the most worrisome side effect of tamoxifen
      is its ability to increase the rates of uterine cancers. It has been claimed that
      most of these cancers are found at an early stage because of vaginal bleeding.
      Moreover, it has been shown that for most women transvaginal ultrasound is an
      ineffective screening method for the early detection of uterine carcinomas. It is
      important, however, to notice that long term tamoxifen treatment can cause
      metastatic uterine cancer--not only carcinomas but also sarcomas (mainly
      malignant mixed mesodermal tumors. It should be noted that, at least for the
      special population of BRCA mutation carriers, transvaginal ultrasound can
      increase our ability for the earlier discovery of ovarian cancer. Thus, we
      believe that there is still a place for the use of transvaginal ultrasound in
      special populations. This is specifically for long term tamoxifen users (more
      than the usually recommended five years), women with a higher chance of having
      uterine carcinomas (namely very high body weight, strong family history) and
      women with a high index of suspicion as carriers of a BRCA mutation. Until new
      second generation SERMs and aromatase inhibitors are shown to possess better anti
      cancer abilities than tamoxifen, this drug will remain in wide use, however, we
      must not overlook its possible rare side effects.

PMID- 12222138
TI  - [The pathophysiology of ascites formation in cirrhosis of the liver].
AB  - Ascites is the most common complication in cirrhotic patients. The presence of
      ascites predisposes the cirrhotic patients to complications that significantly
      increase their morbidity and mortality. These include spontaneous bacterial
      peritonitis and the hepato-renal syndrome. The ascitic process has different
      stages, from the diuretic responsive ascites through the unresponsive ascites to
      the development of the hepato-renal syndrome. Until a few years ago there was a
      controversy regarding the pathophysiology of ascites in portal hypertension.
      Nowadays, the peripheral vasodilatation theory is accepted as the mechanism
      responsible for the development of the ascites. This theory proposes that
      elevated blood levels of vasodilators cause a systemic vasodilatation, that leads
      to the development of a hyperdynamic circulation. This vasodilatation causes
      activation of compensatory vasoconstrictive mechanisms. The vasoconstrictors
      cause functional kidney damage, which leads to the retention of sodium and water,
      and thus to the development of ascites.

PMID- 12222139
TI  - [False memory syndrome: state of the art].
AB  - The review describes the heated dispute on the present state of recovered
      traumatic memories. There are two main schools concerning the status of recovered
      memories of child abuse. One school believes in their authenticity
      unconditionally. Those who oppose the authenticity claim False Memory Syndrome's
      existence. They describe it as "a serious form of psychopathology characterized
      by strongly believed pseudomemories of childhood sexual abuse" and "condition in
      which a person's identity and interpersonal relationships are centered around a
      memory of traumatic experience which is objectively false but in which the person
      strongly believes". This review presents the allegations of both sides involved
      in the dispute, with updates of scientific and judicial references and relevant
      recommendations to care takers.

PMID- 12222140
TI  - [Diagnosis of drug hypersensitivity--state of the art].
AB  - Adverse drug reactions are ubiquitous in outpatient as well as inpatient clinical
      care. An allergic drug reaction is an immunologically mediated adverse drug
      reaction that exhibits specificity and recurrence on re-exposure to the offending
      drug. The diagnosis and treatment of drug allergies is limited by a number of
      factors. In most instances the exact epitope causing the reaction is unknown, the
      immunological mechanism is unclear, the presence of immunological recognition is
      not predictive of a clinical reaction and the gold standard for diagnosis, the
      drug challenge, a complicated and sometimes dangerous endeavor. Nevertheless,
      during the past few years a serious attempt at standardization and validation of
      in vitro and in vivo techniques for the diagnosis of drug allergies, has been in
      progress. New methods, like the basophil surface marker for activation, CD63 are
      replacing old ones like histamine release for immediate type hypersensitivity
      reactions. For instance, in the field of beta-lactam hypersensitivity, the
      specific epitopes are better defined and standardized protocols for both
      immediate and delayed type reactions are in the process of being introduced. A
      standardized European Network of Drug Allergies (ENDA) questioner, published in
      1999, permits systematic data gathering of events surrounding the acute drug
      reaction, facilitating later immunological investigation and diagnosis. This
      review attempts to summarize the present and some of the future options in the
      diagnosis of this common iatrogenic complication.

PMID- 12222141
TI  - [Dermatological manifestations of smoking].
AB  - Heavy smokers are at risk of aggravating several cutaneous diseases. The main
      adverse effects of cigarette smoking on the skin are associated with psoriasis,
      with squamous cell carcinoma and with the poorer outcome of malignant melanoma.
      One of the main concerns to smokers is the well-documented effect of smoking on
      premature face aging due to excessive wrinkling, which may follow enhanced
      elastase activity, and the degradation of elastin in the dermis. Recently,
      evidence has emerged indicating that smoking induces in the skin the activity of
      the metallo-proteinase MMP-1 that specifically degrades collagen, the most
      abundant protein in the cutaneous matrix.

PMID- 12222142
TI  - [What's hidden in the bleeding cup?].

PMID- 12222143
TI  - The crisis continues.

PMID- 12222144
TI  - Doctors needing lawyers: the legal role of medical societies.

PMID- 12222146
TI  - File your prompt pay complaints.

PMID- 12222145
TI  - The snake still bites.

PMID- 12222147
TI  - History of the Tennessee radiological society, 1934-2000.

PMID- 12222148
TI  - Bioterrorism: public health 101 with a twist.

PMID- 12222149
TI  - US Supreme Court rules that execution of defendants with mental retardation is
      unconstitutional.

PMID- 12222150
TI  - Bibliography. Current world literature. Respiratory system.

PMID- 12222151
TI  - You're welcome.

PMID- 12222152
TI  - Cancer update.

PMID- 12222153
TI  - Sharp practice.

PMID- 12222154
TI  - [Malignant Lymphoma Conference. 25-27 April 2002, Szeged. Abstracts].

PMID- 12222155
TI  - Workshop report. Children as a special subpopulation: focus on immunotoxicity.
      Federal Institute for Health Protection of Consumers and Veterinary Medicine
      (BgVV), 15-16 November 2001, Berlin, Germany.
AB  - An international symposium on the impact of environmental hazards, chemicals and
      drugs on the developing immune system of children was held in Berlin (Germany)
      organized by the BgVV. Epidemiological evidence indicates that an immature immune
      system challenged early in life by bacterial antigens may prevent, to some
      extent, allergic reactions including asthma bronchiale triggered by environmental
      pollutants. However, the prevalence for infectious disease is increased in
      childhood, especially when exposure to contaminants takes place in the period of
      pregnancy and breast-feeding. The effects of chlorinated biphenyls, dioxin,
      endotoxins, hexachlorobenzene, and direct and indirect in utero tobacco smoke
      exposure are examples. All participants recommend comparative and follow-up
      epidemiological studies and clinical examination of infants and children at risk
      during upbringing. There is ample evidence from experimental studies that
      indicates adverse effects on the developing immune system after in utero and
      postnatal exposure to chemicals and drugs. The adverse reactions of aciclovir,
      benzodiazepines, hexachlorobenzene, organotins (di-n-octyltin dichloride,
      tributyltin oxide), pesticides (methoxychlor, heptachlor) and polyhalogenated
      aromatic hydrocarbons (2,3,7,8-tetrachlorodibenzo-p-dioxin) are presented and
      reviewed. To determine the predictive value of test data in risk assessment for
      neonates and children, development, differentiation and maturation of the immune
      system in humans and laboratory rodents is compared in their pre- and postnatal
      stages. Considering some differences in immunocompetence at birth and after
      lactation, and differences in the time frame for maturation of the immune system,
      reaction types are thought to be common, comparable and similar in human
      childhood and early adolescence and the postnatal lifetime of laboratory rodents.
      The participants of the symposium felt strongly that regulatory steps urgently
      need to be initiated to incorporate some relevant aspects into existing test
      guidelines for testing developmental immunotoxicity. In this context, it is
      recommended that animals culled otherwise in one- and two-generation studies be
      examined for developmental immunotoxicity according to the valid methods and
      parameters discussed. The majority of participants agreed that a safety factor of
      10 is too low in risk assessment and management to protect a sensitive
      subpopulation of children against man-made environmental pollutants.

PMID- 12222156
TI  - The fate and growth of general surgery in the United States.

PMID- 12222157
TI  - Perinatal care improves the outcome of triplets.
AB  - OBJECTIVE: To compare pregnancy complications and neonatal outcome of 85 triplet
      gestations cared for during the 15 years in a single perinatal unit. METHODS:
      Pregnancies were divided in two groups according to the differences in the
      management plan and their outcomes were compared. Group I (N = 44) consisted of
      pregnancies cared from 1986 to 1995, using standard model of care: preventive
      hospitalization from the early second trimester or home bed rest with routine
      hospitalization after 28-32 weeks of pregnancy, routine clinical and ultrasound
      examinations, biophysical profile and non-stress tests starting at 28 weeks,
      expert neonatal care without free access to surfactant or to parenteral
      nutrition. Group II (N = 41) consisted of pregnancies cared for from 1986 to 2000
      using modified care: preventive hospitalization from early second trimester or
      home bed rest with routine hospitalization after 32 weeks of pregnancy,
      biophysical profile, non-stress tests and pulsed doppler analysis of fetal
      umbilical artery, fetal aorta and middle cerebral artery blood flow from as early
      as 26 weeks, and neonatal care improved by free access to surfactant and
      parenteral nutrition. RESULTS: The mean gestational age, mean birth weight, the
      proportion of growth-retarded infants, the incidence of various maternal
      complications and immediate neonatal conditions as judged by APGAR scores did not
      differ between the groups. The incidence of deliveries up to 28 weeks was lower
      in the group II in comparison to group I, but the proportion of term and near
      term deliveries was lower. The incidence of cesarean sections was high (91.8%),
      but significantly increased cesarean delivery rate because of fetal distress was
      observed in the group II (P = 0.014). Infants in the group II had less frequently
      uneventful early neonatal period, mainly due to significantly increased conatal
      infection (P = 0.007) and neonatal encephalopathy rate (P = 0.001). However,
      perinatal mortality was decreased from 235% in the group I to 142% in the group
      II for newborns that reached 24 weeks of gestation or more. The decrease of
      perinatal mortality was observed also in the newborns born after 28 weeks of
      gestation (123% in the group I and 99% in the group II). None of the children
      weighing <1000 g died in utero in the group II. Early neonatal death of infants
      weighing >1500 g was significantly reduced in the group II (P = 0.048).
      CONCLUSION: Advances in neonatal care, but also the delivery of infants in better
      overall condition must be the explanation for improved outcome of triplet
      gestations managed by modified care. A higher cesarean section rate because of
      imminent fetal jeopardy as judged by not only fetal heart rate tracings, but also
      umbilical, aortic and middle cerebral artery flow analysis, could be the
      explanation for lowered perinatal mortality and significantly improved outcome in
      very preterm infants from triplet gestations.

PMID- 12222158
TI  - The great debate: Psychosocial interventions can improve clinical outcomes in
      organic disease. Presented at the annual meeting of the American Psychosomatic
      Society, Monterey, California, March 9, 2001.

PMID- 12222159
TI  - [Diffuse idiopathic skeletal hyperostosis (DISH)].

PMID- 12222160
TI  - Stupidity and mental illness.

PMID- 12222161
TI  - Hey, Doc! Just another detox?

PMID- 12222162
TI  - Introducing Health Sector Reform and Priority Health Services.

PMID- 12222163
TI  - 22 countries: tax relief for vaccines, ORS, and contraceptives.

PMID- 12222164
TI  - India: using stakeholder analysis to forecast success.

PMID- 12222166
TI  - 78 countries: immunization financing in developing and transitional countries.

PMID- 12222165
TI  - Bolivia: a mid-course assessment of the National Mother Child Health Insurance
      Program.

PMID- 12222167
TI  - Safe motherhood: reforming maternal and reproductive health care.

PMID- 12222168
TI  - Uganda: improving maternal health care efficiency and financing.

PMID- 12222169
TI  - Bangladesh: actions for sustainable immunization services.

PMID- 12222170
TI  - Planning the 1991 census.
AB  - This article describes the plans being made by the census offices in the United
      Kingdom for the 1991 census "particularly for the topic content of the Census,
      for its geographical base and for the dissemination of results, and how users of
      census statistics are being consulted about their needs."

PMID- 12222171
TI  - Digital boundaries for the 1991 census of population in Scotland.

PMID- 12222172
TI  - To be or not to be--what are the odds?

PMID- 12222173
TI  - Trend in suicide in England and Wales, 1982-96.

PMID- 12222174
TI  - A comparison of the census characteristics of respondents and non-respondents to
      the 1981 General Household Survey (GHS).
AB  - "The purpose of this study was to investigate the effects of non-response on the
      representiveness of the GHS [General Household Survey] achieved sample by
      comparing respondents and non-respondents to the 1981 GHS in terms of their
      characteristics as recorded in the 1981 [United Kingdom] Census of Population." 
      The predominant finding is that "households containing dependent children and
      individuals in age-groups most often found in such households were over
      represented in the sample and non-family households and individuals in some of
      the older age-groups under-represented."

PMID- 12222175
TI  - Mapping and analysing 200 years of the census.
AB  - "The 10th of March 2001 will mark the two-hundredth anniversary of the first
      census of population and should be an opportunity to look back not merely at the
      history of census-gathering but at the development of the population, economy and
      society of the British Isles. [We describe] a major university-based project led
      by ourselves and funded by the Economic and Social Research Council, the
      Leverhulme Trust and other bodies.... The project is supported by ONS [Office for
      National Statistics] and one of our central goals is to create an historical
      social atlas for publication at the bi-centenary."

PMID- 12222176
TI  - Projections of the population by marital condition.

PMID- 12222177
TI  - New methods for surveying health risks at work.

PMID- 12222178
TI  - Migration assumptions for sub-national population projections.

PMID- 12222179
TI  - Postcodes in the 1981 census of Scotland.

PMID- 12222180
TI  - Migration assumptions for the 1979 based sub-national population projections.

PMID- 12222181
TI  - OPCS and the 1981 census.

PMID- 12222182
TI  - Demographic projections.

PMID- 12222183
TI  - Statistics Users' Conference on the census of population and associated social
      statistics.

PMID- 12222185
TI  - Department of the Environment (DOE) household projections.
AB  - "This article briefly describes the basis of the method of household projections
      developed by the Department of the Environment and touches on some of the
      problems and shortcomings."  The projections concern England and Wales only.

PMID- 12222184
TI  - A new method for estimating the trend in the fertility rate.
AB  - "This article describes the method devised by Gerard Calot...for estimating
      monthly TPFRs [total period fertility rates] when only provisional monthly
      figures for numbers of births are available.  The application of the Calot
      method, together with the US Bureau of the Census X-11 seasonal adjustment
      package, for computing the trend in the England and Wales fertility rate is also
      described."

PMID- 12222186
TI  - [Decree No. 1010 of 5 September 1989 approving Regulations on ordinary passports,
      travel documents, and travel papers for foreigners; repealing Decree No. 676 of
      15 February 1966 of the Ministry of Justice and amending Decree No. 172 of 23
      March 1977 of the Ministry of Foreign Relations].

PMID- 12222187
TI  - [Act No. 19.023 of 26 December 1990 establishing the National Women's Service].

PMID- 12222188
TI  - [Act No. 18.994 of 14 August 1990, creating the National Office for Returned
      Persons, establishing its objectives, functions, and organization, and specifying
      its personnel plan].

PMID- 12222189
TI  - [Decree No. 1.373 of 29 October 1990 establishing support systems for the care of
      minors in irregular situations].

PMID- 12222190
TI  - [Decree No. 338 of 26 September 1989 providing that vaccinations against
      preventable diseases are required for the country's children].

PMID- 12222191
TI  - [Law No. 19.042 of 1 February 1991 creating the National Youth Institute].

PMID- 12222192
TI  - Dollars and sense. Efforts to reduce perinatal transmission fuel the debate over
      "haves" and "have nots".

PMID- 12222193
TI  - Activism needed for vaccines to reach South.

PMID- 12222194
TI  - Lessons from African STD trials noted by US researchers.

PMID- 12222195
TI  - War, oppression, refugee camps fuel spread of HIV. Migration and HIV.

PMID- 12222196
TI  - Affordable TB treatments. South.

PMID- 12222197
TI  - Harm reduction in developing countries.

PMID- 12222198
TI  - Non-adherence: the Achilles heel of multiple-drug therapies.

PMID- 12222200
TI  - Ugandan study shows no link between coercion and HIV.

PMID- 12222199
TI  - Orphans: "Our children, our future".

PMID- 12222201
TI  - Condom use soars after intervention, China.

PMID- 12222202
TI  - The profile of a campaign: "Men Too".

PMID- 12222203
TI  - Danish pharmacies give "straight facts about contraception".

PMID- 12222204
TI  - World contraceptive use in 1987.

PMID- 12222205
TI  - Population and policy in Finland.

PMID- 12222206
TI  - Can midwives be trained to insert IUDS? Results from Turkey.

PMID- 12222207
TI  - Epidemiological and preventive aspects of HIV infection.

PMID- 12222208
TI  - Survey of central and eastern Europe (part I), a textbook case.

PMID- 12222209
TI  - Poland's other Thirty Years' War.

PMID- 12222210
TI  - "A responsibility for the whole society"--how the government tackles family
      planning in the German Democratic Republic.

PMID- 12222211
TI  - A new era begins: an official statement by Romanian Vice-Minister of Health
      Professor Bogdan Marinescu.

PMID- 12222212
TI  - Bucharest's first family planning clinic since the revolution.

PMID- 12222213
TI  - Romania ends compulsory childbearing.

PMID- 12222214
TI  - Can the Danish abortion rate be changed?

PMID- 12222215
TI  - Improving the care of the young abortion patient in Finland.

PMID- 12222216
TI  - Pointers on progress in family planning in Portugal.

PMID- 12222217
TI  - Planning for life in Latin America.

PMID- 12222218
TI  - Facts of life for adults.

PMID- 12222219
TI  - Europe's youth: are they all alike?

PMID- 12222220
TI  - Netherlands: study of teenagers gives pointers for better sex education.

PMID- 12222221
TI  - Sweden. Swedes take the lead in interpersonal relations.

PMID- 12222222
TI  - New methods could test male responsibility.

PMID- 12222223
TI  - Metamorphosis of the FPA.

PMID- 12222224
TI  - Time to end bias against the pill.

PMID- 12222225
TI  - The pill is good for you.

PMID- 12222226
TI  - Method selection made easy.

PMID- 12222227
TI  - Welcome visitors.

PMID- 12222228
TI  - Female condom improves with use.

PMID- 12222229
TI  - Two routes, same destination.

PMID- 12222230
TI  - UK Health Secretary launches family planning initiatives.

PMID- 12222231
TI  - Waltz of the couples: change partners, please.

PMID- 12222232
TI  - Born in Scandinavia: either side of the blanket will do.

PMID- 12222233
TI  - Tomorrow may be too late.

PMID- 12222234
TI  - Blurred edges to population policies.
AB  - Fertility is now below replacement level in most European countries, especially
      the industrialized ones.  In the last 20 years, several countries have developed
      or improved pronatalist programs containing incentives that are designed to
      motivate couples to have a 2nd and especially a 3rd child, to maintain a stable
      population.  The WHO Sexuality and Family Planning Unit called a short
      consultation on this subject last October.  What actually constitutes a
      pronatalist population program and the connections between public policies and
      private reproductive behavior were not very clear.  Nor is it easy to assess the
      longer--term demographic effects of pronatalist policies or what influences their
      effectiveness.  The outcome usually reflects the country's history, cultural and
      religious traditions, changes in lifestyle, and the value given to the family and
      children.  Incentives are defined as monetary or nonmonetary inducements to
      voluntary reproductive behavior that conforms to specified population policies. 
      They may be small or large, in cash or kind, parity-specific or income-linked,
      immediate or developed, one-time or incremental, or any combination of these. 
      Disincentives are negative sanctions that are either incurred or thought likely
      as a result of violating the policy. But both incentives and disincentives are
      difficult to define. Pronatalist policies designed to encourage early marriage
      and larger families, thereby raising the future total fertility rate should not
      be confused with traditional social welfare policies designed simply to ease the
      burden of childbearing.  Some policies have both demographic and social welfare
      aims.  Strong pronatalist policies may be linked with restrictions on
      contraceptive availability and legal abortion. Moreover, other public policies
      affecting social security, education, employment, housing, regional planning and
      the emancipation of women may unintentionally influence demographic behavior. 
      Population policies are the product of politics.  Often written in ambiguous
      language and intended to affect society as a whole, they still depend for their
      outcome on microlevel changes in a couple's perceptions of the costs and benefits
      of having children.  In theory, they can be carried out in many ways but in
      practice such policies are severely limited by administrative, political,
      technological, economic, and ethical constraints.  One difficulty is that
      governments is rarely enunciate precise goals.  Their approach may range from
      noninterference in private reproductive behavior to total coercion using controls
      ranging from traditional cultural influences to imposition of fertility
      regulations. In some countries, fertility rates have increased briefly (in terms
      of period rates) following introduction of pronatalist policies.  However, it is
      not clear how the rates were influenced, particularly in the case of parities 1,
      2, and 3.  A forthcoming report will describe experiences in Bulgaria, France,
      Germany, Sweden, and Norway.

PMID- 12222235
TI  - Ireland: child rape case undermines abortion ban.

PMID- 12222236
TI  - Padlocked societies.

PMID- 12222237
TI  - Adolescents and contraceptive advice.

PMID- 12222238
TI  - Abortion law in Poland.
AB  - The Polish Senate has passed the Abortion Law without modification and by 1 vote.
      This means that indications for legal termination of pregnancy include threat to
      life and health of the mother, pregnancy resulting from criminal activity, and
      congenital disorder of the fetus. Social indications will no longer be consistent
      with the law. Concerning sex education and family planning, Article 2, point 2 of
      the law status that the local authorities according to their terms of references,
      defined elsewhere, are obliged to ensure unhindered access to method and articles
      used in informed parenthood.  In Article 4 sex education, information concerning
      informed and responsible parenthood, family values, life in-utero, and methods of
      informed procreation will be introduced into the school curriculum.  The
      responsibility for the details of the curriculum will rest with the Minister of
      Education.  The Law requires the President's signature before its contents can be
      implemented.

PMID- 12222239
TI  - New abortion law in Hungary.
AB  - In December 1992, the Hungarian Parliament revised the abortion law. The new law
      is in some ways more liberal than the former one.  A woman can now have an
      abortion on demand within the first 12 weeks of pregnancy, if she is in a "crisis
      situation".  A compulsory consultation has also been introduced with a nurse who
      informs the women on issues of contraception, maternity allowance, etc.  Under
      certain circumstances abortion is legal beyond the first trimester.  These
      include for example misdiagnoses of the pregnancy, if the women is under 18
      years, or in case of genetical or teratogenic risks.  Abortion performed for
      medical reasons is free of charge.  In other cases the fee is HUF 5000, the
      equivalent of US $60, which can be reduced according to the economical status of
      the family.  In one way the new law can be considered more restrictive;
      previously, an abortion was free of charge for women who became pregnant with an
      IUD, whereas now the woman has to pay the abortion fee.

PMID- 12222240
TI  - Control of fertility in the People's Republic of China.

PMID- 12222241
TI  - The scheduler, the register and the monthly report card.

PMID- 12222242
TI  - Family planning in Europe.

PMID- 12222243
TI  - The access to contraception and sterilization.

PMID- 12222244
TI  - A system of registration and statistics.

PMID- 12222245
TI  - Access to abortion: the legal context, practice and frequency of recourse.

PMID- 12222246
TI  - Family planning in Maghreb: redefining responsibility.

PMID- 12222247
TI  - Men and family planning in Portugal.

PMID- 12222248
TI  - Dutch male teenagers on their role in prevention.

PMID- 12222249
TI  - The impact of voluntary induced abortions on fertility in Israel.

PMID- 12222250
TI  - Return to joint parental responsibility.

PMID- 12222251
TI  - [An active Romanian organization: SECS].

PMID- 12222253
TI  - [Note from Estonia: from abortion to contraception].

PMID- 12222252
TI  - [Family planning services utilization increases for migrant workers].

PMID- 12222254
TI  - [Vietnam: excessive practice of abortion].

PMID- 12222255
TI  - [Legislation concerning reproductive health in Central and Eastern Europe: new
      facts].

PMID- 12222256
TI  - The AIDS era: new challenges and new roles for sexually active teenagers.

PMID- 12222257
TI  - City profile: Almaty, Kazakhstan.

PMID- 12222258
TI  - Family planning and reproductive health in CCEE / NIS.

PMID- 12222260
TI  - IMAP on emergency contraception. Statement developed by the International Medical
      Advisory Panel to IPPF (IMAP), 1994.

PMID- 12222259
TI  - UN to pool resources in battle against AIDS.

PMID- 12222261
TI  - Editorial.

PMID- 12222262
TI  - Implementing the ICPD Plan of Action in Central Asian Republics and Kazakhstan
      (CARAK). Kazakhstan. Looming.

PMID- 12222263
TI  - Implementing the ICPD Plan of Action in Central Asian Republics and Kazakhstan
      (CARAK). Tajikistan. Succeeding against the odds.

PMID- 12222264
TI  - Implementing the ICPD Plan of Action in Central Asian Republics and Kazakhstan
      (CARAK). Kyrgyzstan. Breast-feeding is best.

PMID- 12222265
TI  - Implementing the ICPD Plan of Action in Central Asian Republics and Kazakhstan
      (CARAK). Turkmenistan. Abortion rate declines.

PMID- 12222266
TI  - Implementing the ICPD Plan of Action in Central Asian Republics and Kazakhstan
      (CARAK). Azerbaijan. Urgent need for family planning.

PMID- 12222267
TI  - Putting the ICPD Plan of Action to work. Turkey. Women's health tops the agenda.

PMID- 12222268
TI  - Moldova. Historic regional conference.

PMID- 12222269
TI  - Teenage fertility in the European Union.

PMID- 12222270
TI  - Long-term use of three-monthly injectable contraceptive DMPA not linked to breast
      cancer.

PMID- 12222271
TI  - From family planning to reproductive health. What does it mean?

PMID- 12222272
TI  - Women and AIDS: a growing threat.

PMID- 12222273
TI  - Men's role in reproductive health: family planning is a family affair.

PMID- 12222274
TI  - Country news: focus on Moldova.

PMID- 12222275
TI  - Male participation and responsibility in fertility regulation. Research.
AB  - Women's health advocates have consistently called for men to take more personal
      responsibility for reproductive health and fertility regulation.  The
      UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research
      Training in Human Reproduction has carried out several studies on men's needs and
      preferences with regard to methods of fertility regulation, especially in less
      developed countries.  Although there were significant intercountry differences, a
      high percentage of men studied knew at least one method of fertility regulation,
      most often the condom.  On average, some 75% of men approved of the use of family
      planning, even in developing countries, which is contrary to the commonly held
      notion that men in these countries are against family planning.  It is not clear
      from the data, however, how many men approve the use of male methods, but in
      spite of this, the actual use of such methods was very low.  Condom use was low
      even in the countries that are relatively more effected by the AIDS pandemic. 
      Vasectomy use remains negligible in Africa (0.1%) and Latin America (1%),
      although it was used by 10% of respondents in East Asia.

PMID- 12222276
TI  - Contraceptive research and development.

PMID- 12222277
TI  - Reproductive health in Europe. In every country -- for every age group.

PMID- 12222278
TI  - Reproductive health in Europe. Different problems need different solutions.

PMID- 12222279
TI  - Sexually transmitted diseases (STDs) epidemic in eastern Europe: a call for help.

PMID- 12222280
TI  - Family planning and lifestyles in Germany.

PMID- 12222281
TI  - The effects of the 1993 anti-abortion law in Poland.

PMID- 12222282
TI  - The story of abortion law in Poland.

PMID- 12222284
TI  - Screening for breast and cervical cancer in Europe. Hungary.

PMID- 12222283
TI  - Epidemiology of abortions in Russia.

PMID- 12222285
TI  - Oral contraceptives not a risk factor for cardiovascular disease.

PMID- 12222286
TI  - A pilot survey on abortions among young Armenian women.

PMID- 12222287
TI  - WHO approves three-year integrated plan of action on violence prevention and
      health. Women's health and development.

PMID- 12222288
TI  - HIV - STDs. Making integration work.

PMID- 12222289
TI  - Community-based distribution projects in Turkey. Progress in reproductive health
      practice.

PMID- 12222290
TI  - Young people in Europe. Adolescent health -- sex education.

PMID- 12222291
TI  - Bosnia-Herzegovina: a case study in service collapse. Safe motherhood.

PMID- 12222292
TI  - Slipping through the safety net. Adolescent health / sex education.

PMID- 12222293
TI  - Peer education in Portugal. Adolescent health / sex education.

PMID- 12222295
TI  - What is female genital mutilation?

PMID- 12222294
TI  - Multicultural health promotion: are we getting it right? HIV - STDs.

PMID- 12222296
TI  - How a midwife can change attitudes.

PMID- 12222297
TI  - Women doctors campaign against female circumcision.

PMID- 12222298
TI  - When disaster strikes: caring for mothers and babies in conflict and disasters.

PMID- 12222299
TI  - Prevention of HIV transmission from mother to child: meeting on planning for
      programme implementation, Geneva, 23-24 March 1998. Meeting statement.

PMID- 12222300
TI  - Should emergency contraceptive pills be available without prescription in Europe?

PMID- 12222301
TI  - Emergency contraception: a brighter future?

PMID- 12222302
TI  - Consortium for Emergency Contraception.

PMID- 12222303
TI  - Emergency contraceptive pills: what you need to know. Brochure for programs
      providing combined ECPs.

PMID- 12222304
TI  - Pregnancy is special: let's make it safe.

PMID- 12222305
TI  - The Reproductive Health for Refugees Consortium.

PMID- 12222306
TI  - Armenia: reducing morbidity due to STDs.

PMID- 12222307
TI  - Tajikistan: STD survey results.

PMID- 12222308
TI  - Kyrgyzstan: STD management during the syphilis outbreak.

PMID- 12222309
TI  - Kyrgyzstan: WHO initiated projects on STD control and prevention.

PMID- 12222310
TI  - Yugoslavia: preventing the spread of HIV and STDs.

PMID- 12222311
TI  - Bulgaria: sexually transmitted diseases.

PMID- 12222312
TI  - Albania: STDs and youth culture.

PMID- 12222313
TI  - Bulgaria, the challenge: new approach for minority issues.

PMID- 12222315
TI  - Catholic support for the ICPD programme of action.

PMID- 12222314
TI  - Spotlight on Georgia.

PMID- 12222316
TI  - Poverty, income and ill health.

PMID- 12222318
TI  - Scotland: inequalities in women's reproductive health.

PMID- 12222317
TI  - Targeting reproductive health to reduce poverty.

PMID- 12222319
TI  - Spotlight on Bulgaria.

PMID- 12222320
TI  - Taking action against violence.

PMID- 12222321
TI  - Bulgaria: educating cadets to prevent the spread of STIs.

PMID- 12222322
TI  - Sexual and reproductive health. Are men indispensable?

PMID- 12222323
TI  - Reaching out to men.

PMID- 12222324
TI  - Reproductive health: men's business too.

PMID- 12222325
TI  - The changing role of men since ICPD.

PMID- 12222326
TI  - Advancing reproductive health through human rights and laws.

PMID- 12222327
TI  - Changing tradition -- a Danish approach to female genital mutilation.

PMID- 12222328
TI  - Yugoslavia. "Migration" -- programme activities targeting men.

PMID- 12222329
TI  - Postcoital contraception: a report from the London Brook Advisory Centres, United
      Kingdom.

PMID- 12222330
TI  - Approaches to patients with HIV-related problems.

PMID- 12222331
TI  - Infertility and family planning.

PMID- 12222333
TI  - An unknown dimension in Turkey.

PMID- 12222332
TI  - Once-a-month estrogen/progestogen injectables.

PMID- 12222334
TI  - Implementing the ICPD Plan of Action in Central Asian Republics and Kazakhstan
      (CARAK). Uzbekistan. Squaring up to a demographic crisis.

PMID- 12222335
TI  - Advances in female sterilisation research.

PMID- 12222336
TI  - Reproductive health and family planning in Bosnia and Herzegovina. Results from
      the first year of a post-war programme.

PMID- 12222337
TI  - FORWARD against female genital mutilation.

PMID- 12222338
TI  - Emergency contraception: the users and the services.

PMID- 12222339
TI  - Highlight on women's health -- Ukraine.

PMID- 12222340
TI  - Family planning in the USSR. Sky-high abortion rates reflect dire lack of choice.

PMID- 12222341
TI  - A brighter future for three million Romanian women?

PMID- 12222342
TI  - From Cairo to Copenhagen.

PMID- 12222343
TI  - Fertility behaviour in Flanders: two decades of research.

PMID- 12222344
TI  - Psychographic predictors of risky sexual practice.

PMID- 12222345
TI  - Sexual health education: lower risk.

PMID- 12222346
TI  - Young people: force for change.

PMID- 12222347
TI  - HIV / AIDS and the young: three studies in Southern Africa.

PMID- 12222348
TI  - Attacking AIDS in Uganda.

PMID- 12222349
TI  - Listen, learn, live! World AIDS Campaign 1999 with children and young people.

PMID- 12222350
TI  - Men, sex and AIDS: a pilot study.

PMID- 12222351
TI  - Criminalising unprotected sex.

PMID- 12222352
TI  - New materials for AIDS education at school.
AB  - According to a newly-published Joint UN Programme on HIV/AIDS (UNAIDS) review of
      data from four continents, good-quality sex education helps delay first
      intercourse and leads to lower levels of teenage pregnancy and sexually
      transmitted diseases (STDs). The following materials may be useful: 1) Learning
      and teaching about AIDS at school, Geneva: UNAIDS Technical Update, October 1997.
      An eight-page document analyzes why AIDS education in schools is often denied to
      young people and suggests ways to overcome these problems; 2) Integrating HIV/STD
      prevention in the school setting: a position paper, Geneva: UNAIDS, 1997.  This
      is a two-page document with programming principles, best practice to date, and
      goals in school AIDS education, from a life skills perspective; 3) Impact of HIV
      and sexual health education on the sexual behavior of young people: a review
      update, Geneva: UNAIDS, 1997.  From a comprehensive literature review of
      evaluated interventions, 46 are presented that had an impact on behavior. Effects
      on age at first intercourse, sexual activity and protected sex, as well as gender
      and media issues in the context of education programs, are discussed.

PMID- 12222353
TI  - Orphan care as a long-term HIV prevention strategy.

PMID- 12222354
TI  - AIDS and orphans: legal and ethical issues.

PMID- 12222355
TI  - Mother-to-child transmission of HIV: issues and implications for Southern Africa.

PMID- 12222356
TI  - AIDS and African smallholder agriculture.

PMID- 12222357
TI  - Prevention efforts working. UNAIDS focus.

PMID- 12222358
TI  - Mother-to-child transmission intervention.

PMID- 12222359
TI  - The socio-economic impact of adult mortality and morbidity on households in urban
      Zambia.

PMID- 12222360
TI  - The effects of HIV / AIDS on farming systems in eastern Africa.

PMID- 12222361
TI  - HIV and contraception.

PMID- 12222362
TI  - Private sector AIDS policy: a training opportunity.

PMID- 12222363
TI  - Women, violence and HIV / AIDS in Zimbabwe.

PMID- 12222365
TI  - Africa region HIV seroprevalence.

PMID- 12222364
TI  - Vaccines trials and treatment.

PMID- 12222366
TI  - Youth, sex, taboos and condoms.

PMID- 12222367
TI  - Prevention of HIV transmission from mother-to-child.

PMID- 12222368
TI  - HIV counselling and testing in Zambia: the Kara Counselling experience.

PMID- 12222369
TI  - The early socio-demographic impact of the HIV-1 epidemic in rural Zimbabwe.

PMID- 12222370
TI  - Social sciences conference on AIDS.

PMID- 12222371
TI  - Women sex workers and the HIV pandemic: stigma and blame in context.

PMID- 12222372
TI  - Should condoms be available in prisons?

PMID- 12222373
TI  - The female condom.

PMID- 12222374
TI  - AIDS and private health costs in Zimbabwe.

PMID- 12222375
TI  - HIV seroprevalence among pregnant women in Botswana.

PMID- 12222376
TI  - The sexual and economic politics of (re)integration: HIV / AIDS and the question
      of stability in Southern Africa.

PMID- 12222377
TI  - New guide for advocacy on HIV-related human rights.

PMID- 12222378
TI  - Abidjan: new challenges. UNAIDS focus.

PMID- 12222379
TI  - World AIDS Conference 1998: Bridging the Gap.

PMID- 12222380
TI  - Good news from Thailand.

PMID- 12222381
TI  - HIV and breastfeeding: individual and policy dilemmas.

PMID- 12222382
TI  - HIV / AIDS and the law.

PMID- 12222383
TI  - Malawi: HIV surveillance in antenatal women.

PMID- 12222384
TI  - The AIDS epidemic in Africa: openness and human rights.

PMID- 12222385
TI  - Unprecedented emergency in Southern Africa.

PMID- 12222386
TI  - HIV in Namibia.

PMID- 12222387
TI  - Immigration to Israel, I-VI 1990.

PMID- 12222388
TI  - Demographic characteristics of women applying for interruption of pregnancy in
      Israel, 1989.

PMID- 12222389
TI  - Life tables (complete) in Israel, 1986-1990.

PMID- 12222390
TI  - Census of population and housing, 1983:  selected results from complete
      enumeration.

PMID- 12222391
TI  - Marriages and divorces, 1990.

PMID- 12222392
TI  - Census of population and housing, 1983.  Educational level:  selected data from
      the sample enumeration.

PMID- 12222393
TI  - Census of population and housing, 1983.  Households, marriage, couples,
      fertility:  selected data.

PMID- 12222394
TI  - Census of population and housing, 1983.  Internal migration:  selected data from
      the sample enumeration.

PMID- 12222395
TI  - [Law No. 74-1026 of 4 December 1974, containing various provisions pertaining to
      fertility regulation].

PMID- 12222396
TI  - [Order of 12 April 1988 determining laboratories for biological medical testing
      and the categories of persons who may carry out prenatal diagnoses].

PMID- 12222397
TI  - [Order of 10 September 1992 on the possession, distribution, dispensing, and
      administration of the pharmaceutical speciality Mifegyne 200 mg. in tablet form].

PMID- 12222398
TI  - [Ordinance No. 91-240 of 25 February 1991 relating to the Labor Code applicable
      to the Territory of Mayotte].

PMID- 12222399
TI  - [Decree No. 91-272 of 12 March 1991 establishing the operation of the
      consultative committee for the control of immigration and foreigners in French
      Polynesia created by Article 4V of Act No. 90-612 of 12 July 1990].

PMID- 12222400
TI  - [Law No. 92-1446 of 31 December 1992 on employment, the development of part-time
      work, and unemployment insurance].

PMID- 12222401
TI  - [Circular of 27 February 1992 on demonstrations designed to paralyze the
      functioning of centers for induced abortion].

PMID- 12222402
TI  - [Law No. 92-684 of 22 July 1992 reforming provisions of the Penal Code relating
      to the punishment of crimes and misdemeanors committed against persons].

PMID- 12222403
TI  - [Law No. 75-17 of 17 January 1975, concerning the voluntary termination of
      pregnancy].

PMID- 12222404
TI  - Health centres. Stimulus for a new approach.

PMID- 12222405
TI  - Struggle against injustice.

PMID- 12222406
TI  - Health centres. Good management is crucial.

PMID- 12222407
TI  - Health centres. Involving the community.

PMID- 12222408
TI  - Continuing education. Ways of working.

PMID- 12222409
TI  - Learning to let go. Combating inequality.

PMID- 12222410
TI  - Health action is: continuing education for PHC.

PMID- 12222411
TI  - Continuing education. Putting principles into practice.

PMID- 12222412
TI  - Fighting injustice.

PMID- 12222413
TI  - Initiative for change.

PMID- 12222414
TI  - Continuing education. Closing the performance gap.

PMID- 12222415
TI  - Continuing education. The experience of Tanzania.

PMID- 12222416
TI  - Sexual health: working with women.

PMID- 12222418
TI  - Sexual health: understanding sexual health.

PMID- 12222417
TI  - Health action is: more than just a health issue.

PMID- 12222419
TI  - Sexual health: learning to listen.

PMID- 12222420
TI  - Sexual health: getting the message across.

PMID- 12222421
TI  - Involving women.
AB  - I am a primary health care (PHC) coordinator working with the May Day Rural
      project, a local NGO involved in integrated approaches and programs with rural
      communities in the Ga District of the Greater-Accra region in Ghana.  When we
      talk about the community development approach we must first and foremost
      recognize that we are talking about women, because in the developing world
      frequent childbirths mean that her burden of mortality is higher than a man's;
      her workload is extremely heavy--whether in gardening, farming, other household
      duties, caring for the sick, or the rearing of children; she has a key role in
      PHC and community development, because men are always looking for greener
      pastures elsewhere, leaving the women behind.  Women's concerns are critical in
      most health care projects and women and children are their main beneficiaries. 
      Why not include women in the management team, project design, implementation and
      evaluation processes?  That is what the May Day Rural project is practicing,
      encouraging women's participation and creating a relationship of trust.

PMID- 12222422
TI  - Health centres. Potential is still there.

PMID- 12222423
TI  - [Causes and consequences of population change in Taiwan].

PMID- 12222424
TI  - [Population change and social organization].

PMID- 12222425
TI  - [Relationships among demographic, social and economic variables and their policy
      implications in Taiwan].

PMID- 12222426
TI  - [The effect of spouse's age and educational distances on women's fertility
      controlability].

PMID- 12222427
TI  - [[Demographic transition and financial support for the aged in Taiwan]].

PMID- 12222428
TI  - Determinants of cityward migrants' fertility: theory and evidence.

PMID- 12222429
TI  - A study of occupational achievement of migrants to Kaohsiung City, Taiwan.
AB  - "Based on a survey of 452 migrants who moved into Kaohsiung City, Taiwan, in
      1977, this paper tests two major hypotheses of occupational achievement within
      the context of migration.  They are status attainment and information hypotheses.
      Using the Blau-Duncan basic model...[the author finds that] educational
      attainment of migrants is the most important factor in determining an
      individual's occupational achievement.  More importantly, assistance from
      relatives has a negative effect on occupational achievement for rural migrants
      only." (SUMMARY IN CHI)

PMID- 12222430
TI  - Proximate determinants of fertility in Taiwan area.

PMID- 12222431
TI  - Patterns of mortality differentials by marital status in low mortality countries.
AB  - "This study examined mortality differentials by marital status in 11 low
      mortality countries [for the period 1950-1980].  The results show that, in
      general, unmarried populations have a higher mortality rate than that of married
      populations.  A more detailed analysis indicates that each country has its
      distinctive marital mortality features which are associated with cultural regions
      (East and West) but are not related to developmental factors.  When marital
      mortality patterns of the East and West are compared, it demonstrates that
      mortality rates of never-married Asian women are strikingly higher than that of
      their Western counterparts.  This phenomenon has persisted during the last two
      decades.  Two possible cultural interpretations are suggested: differential
      family support theses versus differential marital selection." (SUMMARY IN CHI)

PMID- 12222432
TI  - [The effects of infant and child mortality on fertility in Taiwan].

PMID- 12222433
TI  - Urbanization in Taiwan: 1900-1985.
AB  - This paper reviews previous research and statistical data concerning urbanization
      and its relationship to migration in Taiwan from 1900-1985.  The level of
      urbanization was very low when Taiwan was under Japanese rule.  The low level of
      industrialization and the difficulty of communication and transportation in the
      early stage of development may have impeded migration.  Beginning in 1953, Taiwan
      began a series of economic construction plans.  Modern industries have burgeoned
      in many large cities and their peripheral townships, thus accelerating the
      urbanization process.  The data clearly show that the growth rate of the urban
      population has been much faster than the rate of change in the proportion that is
      urban.  During the 1920-1940 period, the population of Taiwan gradually moved
      from places of early settlement to new city centers or newly developed areas.  It
      is quite clear that the process of metropolitan dispersion has increased with the
      development of urbanization in Taiwan.  The pattern of city growth was not
      consistent from period to period.  It was reverse U-shaped for the 1950-1960
      period, upward-wave-shaped for the 1960-1970 period, and J-shaped for the 1970
      1985 period.  If a longer period (e.g., 1947-1985) was observed, then it became
      upward-wave-shaped again.  It is quite clear that there is no simple relationship
      between city size and city growth.  This relationship is affected by stage of
      development; it also appears to be affected by duration of observation. 
      Generally, the longer the interval observed, and the later the period analyzed,
      the more the upward-wave-shape holds for the relationship.  Many scholars
      maintain that urban growth in developing countries results primarily from the
      natural increase of urban populations.  However, judging from the rapid urban
      growth in Taiwan during the 1953-1985 period, and considering the natural
      increase contributed by migrants in urban areas, it is likely that rural-urban
      migration is a more important source of urban growth.

PMID- 12222435
TI  - Family interventions, life cycle, and reproductive behavior of married couples in
      Thailand.

PMID- 12222434
TI  - [Sex preference in Taiwan--an exploratory study].
AB  - The quality of children has mostly been discussed in so far as it can affect
      fertility.  The sex of children is a particularly important subject in this
      context.  Because a child's sex is stochastically determined, Ben-Porath and
      Welch used the household production approach to identify risky decision points. 
      The purpose of this paper is twofold.  One is to simplify Ben-Porath's and
      Welch's model.  The other is to use KAP data in Taiwan to examine the causes of
      preferring to have at least 1 boy and to test in what direction and the degree to
      which such preferences affect fertility.  The results can be summarized as
      follows:  1) preferring to have at least 1 boy is significant in Taiwan; 2) the
      data support both the assumption of inelastic demand and mild learning; 3)
      concerning the dummy variable for the existence of at least 1 boy preference, it
      can be shown that the regression coefficients for each of family structure,
      wife's education, and husband's occupation were statistically significant at the
      .01 significance level; and 4) when the impact of "at least 1 boy preference" on
      completed family size is concerned, the regression coefficient for the existence
      of at least 1 boy preference is positive as expected and also the most
      significant variable included.

PMID- 12222436
TI  - [[Mainland China's urban population and urbanization level]].
AB  - The author discusses urbanization in the People's Republic of China and problems
      in data analysis "due to the lack of standardized and well-defined terms for the
      urban settlements and urban population on the mainland.  This paper clarifies the
      relationship between geographic units and demographic data, identifies the major
      types of urban population and their characteristics, explains the reasons for the
      differing levels of urbanization revealed in various data sources, and presents a
      comprehensive data series on mainland China's urbanization that best approximates
      reality." (SUMMARY IN ENG)

PMID- 12222437
TI  - [[The effect of demographic variables on the accuracy of migration
      registration]].

PMID- 12222438
TI  - [[Fertility tempo and fertility transition in Taiwan]].

PMID- 12222439
TI  - [Selectivity and differentials by type of move in Taiwan].

PMID- 12222440
TI  - [Social factors and mortality in Taiwan:  analysis of six causes of death in
      small areas].

PMID- 12222441
TI  - [[The effect of demographic structural change on labor utilization in Taiwan]].
AB  - "The purpose of this study is to examine the effect of demographic structural
      change on labor utilization in Taiwan.... Both purging method and decomposing
      rate differences method are used to analyze labor utilization data obtained from
      reports on the Manpower Utilization Survey from 1980 to 1989. The results suggest
      that the age-sex composition change of labor force from 1980 to 1989 pushed down
      the crude rate of labor underutilization in the labor market; the education-sex
      composition change pulled up crude rate of underutilization; and marital status
      sex composition change also pushed down crude underutilization rate.  In sum, the
      demographic structural change of labor force in Taiwan does have [an] obvious
      impact on labor utilization." (SUMMARY IN ENG)

PMID- 12222442
TI  - [[ARIMA modeling of birth, marriage and population growth rates in Taiwan]].
AB  - "In this paper, we will focus on [population growth, birth, and marriage rates in
      Taiwan] and explore [them] in terms of the time series model.  Furthermore, the
      comparison and analysis will be made utilizing [the] univariate ARIMA model,
      transfer function model and multivariate ARIMA model accordingly.  The seasonal
      factor will also be considered.  Lastly, [projections] will be made on the short
      term growth rate of these three indexes, and we will also estimate the monthly
      sum of population of the next two years in Taiwan." (SUMMARY IN ENG)

PMID- 12222443
TI  - Migration selectivity and its consequences on the occupational structure in the
      Taipei metropolis.
AB  - Migrants' destination choices and their consequences are discussed using data for
      Taipei, Taiwan, and its surrounding areas.  "We limit our focus on migration
      selectivity in terms of occupational structure only.... We try to decompose the
      migration selectivity and its consequences by streams and moving
      motivation....[The author concludes that] overall the influence of migration
      selectivity on occupational structures is still dominated by the selectivity due
      to job and education needs." (SUMMARY IN CHI)

PMID- 12222444
TI  - [[Reexamining the model of population density function:  a study of Kaohsiung
      metropolis]].
AB  - "This paper [tests] both Clark's negative exponential model and Newling's
      quadratic exponential model [using data for] population densities in districts of
      Kaohsiung Metropolis [Taiwan].  It proposes four theoretical amendments and
      supplements to the population density function and the related theories."
      (SUMMARY IN ENG)

PMID- 12222445
TI  - [[The relationship between socioeconomic development clusters and migration in
      Taiwan (1979-1988)]].
AB  - "The purpose of this study is to analyze the relationship between socio-economic
      development and migration among different counties in Taiwan.  Based on data of
      1979 and 1988 this study examines the hypothesis that socio-economic development
      had an impact on migration.  Using the method of cluster analysis, we identified
      six clusters of socio-economic development of counties in 1979 and in 1988....
      The examination...indicates that the higher the socio-economic development level,
      the higher the in-migration rate.  In addition, the larger the difference between
      socio-economic clusters, the bigger the migration stream." (SUMMARY IN ENG)

PMID- 12222446
TI  - The factors influence Taiwanese's immigrants adaptation and re-emigration from
      the Republic of South Africa.

PMID- 12222447
TI  - [Active life expectancy in Taiwan:  compression or expansion?].
AB  - "This paper applies the multiple-decrement life table to the analysis of
      mortality and self-reported disability [for Taiwan], annually from 1986 until
      1989.... It was found that during this period of time, the shifts in 'mortality'
      and 'disability' curves conform to the compression hypothesis.  The area in
      between the two curves [has] shrunk in the 4 year period.... The sex differential
      in disability has been examined.  It is concluded that though at the younger ages
      women tend to spend less person-years in disability, the situation is quite
      different at older ages. Women tend to have greater chance [of] and longer
      duration suffering from disability at old age than men." (SUMMARY IN ENG)

PMID- 12222448
TI  - [[The effect of demographic changes on the unemployment rate in Taiwan: 1978
      1990]].
AB  - "The purpose of this paper is to compute the effects of changes in the
      composition of age, sex, and labor force participation rate, and education of
      population and labor force on the overall unemployment rate in Taiwan.  The
      results show that the changes in the composition of age-sex and labor force
      participation rate have had an increasingly significant downward pressure on the
      overall unemployment rate.  However, the compositional changes in...education
      [and sex] have exerted considerable upward pressure on the overall unemployment
      rate...." Recommendations for future policy directions are made. (SUMMARY IN ENG)

PMID- 12222449
TI  - Effects of personal factors on the destination choice patterns of Canadian
      immigrants:  an evaluation within a multivariate framework.
AB  - "The purpose of this paper is to study the effects of personal factors on the
      established destination choice patterns of Canadian immigrants in 1981 within a
      multivariate context, using the micro data in the Public Use Sample (PUS) of the
      1981 Canadian population census.  Six personal attributes encompassing ethnic
      origin, level of education, occupation, class of work, income and period of
      immigration are...used." (SUMMARY IN CHI)

PMID- 12222450
TI  - [[Changes in marital status in Taiwan during the twentieth century]].
AB  - "This study describes...changes in marital status during [the twentieth] century,
      by analyzing each census result conducted during the time of Japanese occupation
      and after the war in Taiwan.  Taking the age specific statistics, which include
      sex ratio, proportion...ever married, the widowed, and the divorced, as well as
      rates of divorce and remarriage, this study presents the marriage patterns in
      terms of formation, dissolution and reformation in Taiwan of this century."
      (SUMMARY IN ENG)

PMID- 12222451
TI  - [Economic development and married women's employment in Taiwan: a study of female
      marginalization].

PMID- 12222452
TI  - Education selectivity in internal migration in mainland China.
AB  - "The purpose of this paper is to study the selectivity in...internal migration in
      Mainland China with respect to the level of education, based on a sample of young
      adults (aged 17-29) taken from the micro data of the 1987 one-percent National
      Population Survey (NPS87)....[We focus first] on the education selectivity in
      migrations among the city, town and rural strata of the urban/rural hierarchy
      [and then examine] the education selectivity in migration among metropolitan,
      coastal and interior regions." (SUMMARY IN CHI)

PMID- 12222453
TI  - Changes in marital life cycle in Taiwan:  1976 and 1989.
AB  - "To improve...understanding of recent developments and thus gain a better
      appreciation of the likely future course of marital events, we apply a marital
      status life table model...to describe the differential risks for persons moving
      from one marital status to another over time.... The findings...point to the
      trends and patterns of marital formation, marital dissolution, and mortality
      experience of Taiwan in 1976 and 1989.  The findings indicate declines in the
      proportion ever marrying and increases in the average age at marriage.  The
      average duration of a marriage and the proportion of cohort life lived in [the]
      married state have been [declining]. The proportion of marriages ending in
      divorce has been rising steadily.... The level, however, is still relatively low
      by international standards." (SUMMARY IN CHI)

PMID- 12222455
TI  - [The employment of married women in Taiwan: its patterns and causes].
AB  - "This research attempts to explore the modes of women's job careers in Taiwan.
      Using the 1991 wave of 'Taiwanese Social Change Surveys' data, we adopt the
      information regarding married female respondents' job history since their
      marriage and found four major modes of job careers in terms of family life
      cycles: never-stop, stop-after-marriage, stop-after-birth, and never on job....
      We further explore the explanatory factors (including individuals' traits, family
      background factors, and current family statuses) with multi-nominal logistic
      models." (SUMMARY IN ENG)

PMID- 12222454
TI  - [[Demographic foundations of elderly living arrangements:  a simulation study of
      intergenerational coresidence]].
AB  - "In this paper we employ family status life tables to assess the effects of
      demographic processes on family composition and to reveal trends in elderly
      living arrangements [in Taiwan]. We found that further declining fertility and
      changing nuptiality are responsible for the prevalence of nuclear family
      composition.  [The] increasing proportion of nuclear families indicates a
      decreasing probability [of] elderly parents living with their married children. 
      In addition, according to the current nuptiality trends, the increasing
      proportion of women of all ages who remain [unmarried] will strengthen its
      effects on family composition in the near future." (SUMMARY IN ENG)

PMID- 12222456
TI  - [The effects of fertility compression on birth sequence and age composition in
      Taiwan: a simulation].
AB  - "Based on the cohort component projection, this paper simulates the effects of
      fertility compression on birth sequence and age composition in Taiwan, and
      explores the implications for social welfare. As a first step, we fix the
      fertility schedule on the age pattern of 1956 while leaving the TFR to shift as
      it was, [and] simulate the single year of age population groups from 1956 to
      1992.... We subsequently assumed a fixed age pattern of fertility, a compressed
      pattern and an expanded pattern in a projection of five year...age groups from
      1997 to 2097."  (SUMMARY IN ENG)

PMID- 12222457
TI  - [A comparative study on aging between Taipei City and Taiwan's rural areas].
AB  - "This paper extends research on the difference in ageing factors between Taipei
      City and Taiwan's rural area in terms of the changes in fertility, mortality, and
      migration rates.... The analysis--based on data collected from 1968-1993
      demographic data in Taiwan-Fukien Demographic Fact Book...provides strong
      evidence that population processes (fertility, mortality, and migration) have
      different influences on the population ageing of Tapei City and Taiwan's rural
      area." (SUMMARY IN ENG)

PMID- 12222458
TI  - Living arrangements and economic support for the elderly in Taiwan.
AB  - "This paper aims to find out the role of living arrangements in economic support
      for the elderly in Taiwan.... To fulfill this goal, primary and secondary sources
      of living costs are used to derive four types of economic support for the
      elderly.... Our analytical results suggest that living arrangements play a role
      of specification. Of the elderly who are not living with children, these have
      substantially greater proportions of the independent type than those living with
      children." (SUMMARY IN CHI)

PMID- 12222459
TI  - [Dependency structure of the elderly: an examination of women's social position
      in Taiwan].
AB  - "The purpose of the paper is to examine the nature and the structure of elderly
      women's dependency [in Taiwan] and the underlying socio-cultural-political
      forces. From the social constructive perspective, we focused on three
      constructive forces--the Chinese patriarchal/patrilocal family system, the gender
      role, and the state policy on elderly welfare. Three types of dependency-
      economic dependency, dependency for personal and health care, and living
      arrangement--were examined." (SUMMARY IN ENG)

PMID- 12222460
TI  - [Marital status and life expectancy].

PMID- 12222461
TI  - Migration into and out of Taiwan, 1895-1944.

PMID- 12222462
TI  - [An exploratory study of job mobility for reworking women in Taiwan].

PMID- 12222463
TI  - [Present forms and future attitudes of the elderly parental support in Taiwan].

PMID- 12222464
TI  - Cosmopolitanizing Australian suburbia: Asian immigration in Sunnybank.

PMID- 12222465
TI  - [Recent migrants from Macau, Hong Kong, and Chinese Mainland to Taiwan].

PMID- 12222466
TI  - A methodology on the metropolitan population estimate on block basis (with a
      concentration on Seoul).

PMID- 12222467
TI  - A study on status of maternal and child health in an urban area.

PMID- 12222468
TI  - The role of family planning communications--an agent of reinforcement or change.

PMID- 12222469
TI  - The value of children of American college students.

PMID- 12222470
TI  - American immigration policy, Chinese immigration, and Chinese concentration in
      New York City.

PMID- 12222471
TI  - [[Age composition and population cycles]].
AB  - The author attempts to correlate the endogenous population cycle with changes in
      age composition by examining population trends in Taiwan.  "It is argued that
      while the size of parental cohort is related to the size of offspring cohort by
      the renewal process, fluctuations in size are correspondingly transmitted and
      averaged time after time."  The concepts of population cycles as a key factor in
      population change is also examined.  (SUMMARY IN ENG)

PMID- 12222472
TI  - Infant mortality levels, patterns, and differentials in Papua New Guinea.

PMID- 12222473
TI  - The population growth of Hong Kong.

PMID- 12222474
TI  - Family structure and fertility in Taiwan: an extension and modification of
      Caldwell's wealth flows theory.

PMID- 12222475
TI  - The socio-economic characteristics and KAP of teenage mothers in Taipei City,
      1978.

PMID- 12222476
TI  - [A study on the stability of first marriage for married women of childbearing age
      in Taiwan area--an exploration from the age of first marriage, dimensions of
      premarried pregnancy, and the way of marriage decision-making].

PMID- 12222477
TI  - [[Differences between registered and self-reported marital status in Taipei
      metropolitan area]].

PMID- 12222478
TI  - [[Population growth and economic development:  a critical review]].

PMID- 12222479
TI  - [Population growth and educational development in Taiwan].

PMID- 12222480
TI  - [[The effect of age-sex composition change in the labor force on inadequate labor
      utilization in Taiwan]].

PMID- 12222481
TI  - Epidemiologic and health transition in Mauritius.

PMID- 12222483
TI  - [[Changes in the labor force in Taiwan:  1979-1990]].
AB  - "The purpose of this paper is to investigate the effect of age composition on
      labor force participation rate as well as the change in age-specific labor force
      participation rate for both males and females in Taiwan.... Data [are] obtained
      from the Taiwan Manpower Utilization Survey from 1979 to 1990.  Results from the
      standardization analyses indicated that the age composition change from 1979 to
      1990 has a leveling effect on the labor force participation rate (LFPR) for both
      males and females. During the period of time, rate of male labor force
      participation has...decreased while female labor force participation rate
      has...increased and then [leveled] off." (SUMMARY IN ENG)

PMID- 12222482
TI  - Extended commuting and migration in the Taipei metropolitan area.

PMID- 12222484
TI  - [Single-parent households in Taiwan: estimation from one percent 1990 census
      data].
AB  - "This research employs one percent [data from the] random sample from the 1990
      Census...in Taiwan...[to estimate] the proportion of single-parent households
      [of]...overall households...as 3.9%.... We also report the frequency and
      percentage distribution of ?single-parent household' by 23 administration
      districts in Taiwan." (SUMMARY IN ENG)

PMID- 12222485
TI  - A probabilistic approach in rural out-migration system.

PMID- 12222486
TI  - Transition and restructuration of German cities.

PMID- 12222487
TI  - Urbanization in Taiwan, 1964-1975.
AB  - "This paper examines levels and rates of urbanization in Taiwan and its ability
      to absorb a growing labor supply in its urban centers.  Urban growth is
      concentrated in the Northern region and in large urban places.  By 1975, half of
      Taiwan's population was located in places of 50,000 or more and 80 percent of the
      total population growth between 1964 and 1975 occurred in urban areas.  Despite
      substantial urban growth and an even more rapid labor force growth, workers were
      absorbed into 'urban' industries and occupations.  Based on this ability to
      absorb, Taiwan does not appear to be overurbanized and seems to fit the Western
      model."  This paper was originally presented at the 1980 Annual Meeting of the
      Population Association of America (see Population Index, Vol. 46, No. 3, Fall
      1980, p. 373).  (summary in CHI)

PMID- 12222488
TI  - [Labor force participation and fertility of married women in Taiwan area
      (author's transl)].

PMID- 12222489
TI  - Modernization and fertility in Puerto Rico: a re-examination.

PMID- 12222490
TI  - [Suburbanization in the Taipei metropolitan area, 1962-1979].

PMID- 12222491
TI  - [Determinants of fertility in Taiwan--a simultaneous model with female labor
      force participation].

PMID- 12222492
TI  - [The distribution and movement of population in Taipei metropolitan area:  the
      analysis of travel demand].

PMID- 12222493
TI  - Marriage practices in contemporary China:  a comparative study of urban and rural
      marriages in Taiwan.

PMID- 12222494
TI  - [Demographic modernization].

PMID- 12222495
TI  - [Projection of primary school enrollments for the Taiwan-Fukien area, 1983-1987].
AB  - A projection of the population of school age in Taiwan is presented for the
      period 1983 to 1987.  Special emphasis is given to the effects of recent
      fertility trends on educational needs.  The projections include information on
      "(1) births corresponding to each academic year, (2) the survival ratio from
      birth to age at entrance, (3) projections of the grade 1 enrollments, (4)
      estimates of median grade-to-grade progression ratios, (5) primary school
      enrollments at each grade, (6) annual increase of students, (7) annual increase
      in number of classes, and (8) annual increase of teachers."  The implications for
      future government spending are considered.  Changes in educational plans to
      conform to available resources are discussed.  (summary in ENG)

PMID- 12222496
TI  - [Changes in the age composition of the Taiwan population, 1905-1979].

PMID- 12222497
TI  - [The formal dynamics of population transition].
AB  - This paper reexamines the facts and theories of the much debated population
      transition and proposes that the transition should be regarded as a "regularity"
      governing the population growth of the nations during the past 200 years.  It is
      argued that in almost all cases the mortality decline has preceded the fertility
      decline but socioeconomic covariates of fertility have been found to be
      inconsistent, a supply dominant resolution with built-in dynamics of the renewal
      process should be adopted.  Fertility decline is then related to a subjective
      increase in the supply of children, and alternatively, to the relative income of
      the young adults entering the labor market.  Evidence affirming the relationships
      between mortality decline, shifting age composition, and fertility decline are
      provided.

PMID- 12222498
TI  - Relationships of population growth and socio-economic development between
      satellite areas and the inner city--Taipei metropolitan case.

PMID- 12222499
TI  - Marital status composition and fertility: a comparative analysis of World
      Fertility Survey data.

PMID- 12222500
TI  - [A study of attitudes and behavior regarding fertility among newlyweds in Taipei
      City].
AB  - There are around 40,000 births in Taipei City each year.  Of them about 40% are
      of the 1st parity.  Of all deliveries, about 80% are born to mothers under 30
      years old.  There are about 20,000 marriages each year.  Of all brides and grooms
      surveyed in the present study, 39.4% and 39.1% consider the ideal time to
      conceive being either as early as possible or within 1 year after the wedding. 
      In actuality, 28.08% of the respondents were already pregnant before the wedding.
      Excluding the inteviewees who were married for over 1 year, 34.1% are currently
      pregnant, 6.98% have already given birth, and 0.15% have become pregnant again
      after a birth.  This result is similar to the findings of the KAP conducted by
      the Center in 1980, which showed that 41.3% of the interviewees gave birth to
      their 1st child within 1 year after the wedding.  The same survey of 1980 also
      finds that the interval between the 1st and the 2nd child is 1.94 years, though
      women in general consider the ideal interval to be 2.6 years.  How to encourage
      those who are to be married and the newlyweds to prolong the intervals between
      the wedding and the 1st child and between the 1st and the 2nd child is an
      important task of the health educators.  The present study interviews 1013
      couples who registered their marriages in October 1983.  Needs, targets, and
      contents of education programs are identified.  Better ways to communicate with
      the newlyweds are also indicated.  The purpose of the study, based on the
      findings, is to propose a model most suitable for the education in family
      planning of those who are to be married and who are just married, in order to
      provide them with better services and to further reduce the fertility of young
      people.

PMID- 12222501
TI  - An appraisal of Hong Kong population projections.

PMID- 12222502
TI  - Future research directions on factors related to fertility decline in Taiwan,
      ROC.

PMID- 12222503
TI  - [The importance, development situation, and trend of population studies].

PMID- 12222504
TI  - Age at first marital union and fertility: evidence from some Asian and Pacific
      countries.

PMID- 12222505
TI  - A study on migration of population in Korea.

PMID- 12222506
TI  - Effects of vasectomy on medical and psychosocial aspects.

PMID- 12222507
TI  - An evaluative study of nurses and midwives trained in comprehensive family
      planning service in the Philippines.

PMID- 12222508
TI  - Malaysian population and family development.

PMID- 12222509
TI  - Effects of incentive on the acceptability of sterilization in rural area in
      Korea.

PMID- 12222510
TI  - The population dynamics in Indonesia.

PMID- 12222511
TI  - Strengthening family planning services by integrating it into existing MCH and
      primary care system.

PMID- 12222512
TI  - Attitudes of religious leaders toward family planning and abortion in Thailand.

PMID- 12222513
TI  - A study on Thai prospective teachers' opinions toward family life and family
      planning including sex education.

PMID- 12222514
TI  - Thailand. AIDS: an attitude problem.

PMID- 12222515
TI  - Abortion rights down under.

PMID- 12222516
TI  - Reproductive health in India.

PMID- 12222517
TI  - Family planning services -- what's new.

PMID- 12222518
TI  - 6000 girls at risk every day. Female genital mutilation, although illegal, is
      still widely practiced.

PMID- 12222519
TI  - Against the law: Irish women and abortion.

PMID- 12222520
TI  - Maternal deaths in Tanzania -- a challenge.

PMID- 12222521
TI  - Editorial.

PMID- 12222522
TI  - Female genital mutilation: strategies for eradication.

PMID- 12222524
TI  - Female genital mutilation protocol for clinic staff.

PMID- 12222523
TI  - Consequences of genital mutilation.

PMID- 12222525
TI  - The African Well Woman's Clinic at Guy's and St Thomas' Hospital Trust.

PMID- 12222526
TI  - Spain. Women in the world.

PMID- 12222527
TI  - The reasons given for FGM: culture and tradition.

PMID- 12222529
TI  - [30th Anniversary of the Institute of Surgery and Transplantology of the Academy
      of Medical Sciences of Ukraine. Abstracts].

PMID- 12222528
TI  - Women's health in Japan.

PMID- 12222530
TI  - Response to Bergeret's "Homosexuality or homoeroticism: 'narcissistic
      eroticism'"(Int.J.Psychoanal., 83:351-62).

PMID- 12222531
TI  - Abstracts of the XXXVII Annual Scientific Meeting of the Society for the
      Spontaneously Hypertensive Rat (SHR). October 5-6, 2001, Nagasaki, Japan.

PMID- 12222532
TI  - [The J.E. Purkyne Czech Medical Society and the Czech Internal Medicine Society
      in cooperation with the Slovak Internal Medicine Society presents the 120th
      Internal Medicine Seminar. "Nutrition and tumor diseases". Held 29 November 2001
      at Hradec Kralove].

PMID- 12222533
TI  - Current readings in nuclear medicine.

PMID- 12222534
TI  - Gene therapy of erectile dysfunction in the rat with penile neuronal nitric oxide
      synthase.
AB  - Gene transfer to the penile corpora cavernosa of constructs of the inducible and
      endothelial nitric oxide synthase (NOS) cDNAs ameliorates erectile dysfunction in
      aged rats. In this study, we investigated whether the neuronal NOS (nNOS) variant
      responsible for erection, penile nNOS (PnNOS), can exert a similar effect, and
      whether the combination of electroporation with a helper-dependent adenovirus
      (AdV) improves gene transfer. PnNOS and beta-galactosidase cDNAs were cloned in
      plasmid (pCMV-PnNOS; pCMV-beta-gal) and "gutless" AdV (AdV-CMV-PnNOS; AdV-CMV
      beta-gal) vectors, and injected into the penis of adult (beta-gal) or aged
      (PnNOS) rats, with or without electroporation. Penile erection was measured at
      different times after PnNOS cDNA injection, by electrical field stimulation of
      the cavernosal nerve. The expression of beta-galactosidase or PnNOS was estimated
      in penile tissue by either histochemistry and luminometry or Western blot, and
      the effects of AdV-CMV-PnNOS on mRNA expression were examined by a DNA
      microarray. We found that electroporation increased pCMV-beta-gal uptake, and its
      expression was detectable at 56 days. In the aged rats treated with pCMV-PnNOS
      and electroporation, the maximal intracavernosal:mean arterial pressure ratios
      were elevated for 11 and 18 days when compared with those in controls.
      Electroporation intensified penile uptake of as few as 10(6) viral particles (vp)
      of AdV-CMV-beta-gal, and with 10(7) vp beta-galactosidase was still detectable at
      60 days. Electroporated AdV-CMV-PnNOS (10(7) vp) was effective at 18 days in
      stimulating the erection of aged rats, without inducing the expression of
      cytotoxic genes. In conclusion, intracavernosal gene therapy with PnNOS cDNA
      corrected the aging-related erectile dysfunction for at least 18 days when given
      by electroporation in a helper-dependent AdV at low viral loads.

PMID- 12222535
TI  - Association for European Paediatric Cardiology XXXVII Annual General Meeting.
      Porto, 15-18 May 2002. Abstracts.

PMID- 12222536
TI  - [Abstracts of the 54th Congress of the German Society of Urology. 18-21 September
      2002, Wiesbaden, Germany].

PMID- 12222537
TI  - Abstracts of the XI International HIV Drug Resistance Workshop: Basic Principles
      and Clinical Implications. 2-5 July 2002, Seville, Spain.

PMID- 12222539
TI  - Abstracts of the Annual Congress of the European Association of Nuclear Medicine.
      August 31-September 4, 2002. Vienna, Austria.

PMID- 12222538
TI  - Abstracts of the 27th European Peptide Symposium. Sorrento, Italy, August 31
      September 6, 2002.

PMID- 12222540
TI  - American Society for Mass Spectrometry directory of members and corporate
      members.

PMID- 12222541
TI  - Evaluation of four once-daily aminoglycoside dosing nomograms.
AB  - STUDY OBJECTIVE: To evaluate the accuracy of four once-daily aminoglycoside
      dosing nomograms in producing the desired gentamicin peak concentration (Cmax)
      target of 20 microg/ml in patients with varying degrees of renal function.
      DESIGN: Retrospective analysis using prospectively collected pharmacokinetic
      data. SETTING: Rural teaching hospital. PATIENTS: Ninety patients receiving
      intravenous gentamicin divided into three groups (30 patients each) determined by
      estimated renal function: group 1, creatinine clearance (Cl(cr),) 60 ml/minute or
      greater; group 2, Cl(cr) 40-59 ml/minute; group 3, Cl(cr) 20-39 ml/minute.
      Intervention. Serum gentamicin concentrations were collected for a 2-point (two
      consecutive infusions and one predose and one postdose concentration sampled
      during steady state) or 3-point (single infusion and one predose and two postdose
      concentrations at least 1.5 estimated half-lives apart) pharmacokinetic study for
      determination of patient-specific pharmacokinetic parameters (elimination rate
      constant, volume of distribution at steady state, and clearance) after 30-minute
      infusions of gentamicin 2.8 +/- 1.6 mg/kg. MEASUREMENTS AND RESULTS: The four
      nomograms evaluated were from Hartford Hospital, Barnes-Jewish Hospital,
      University of Rochester, and the Sanford Guide. With a pharmacokinetic analysis
      program and the patient-specific pharmacokinetic parameters, Cmax and minimum
      concentration (Cmin) were determined with use of the recommended doses and dosing
      intervals of the four nomograms. Also, the gentamicin dose and interval needed to
      achieve a Cmax and Cmin of 20 microg/ml and 0.2 microg/ml, respectively, were
      determined. Dosing was based on total body weight unless that weight was more
      than 25% of ideal body weight, in which case, an adjusted body weight was used.
      In general, the recommended dosages and resultant Cmax produced by the nomograms
      were significantly less (p < 0.05) than the dosage and Cmax actually needed to
      achieve a Cmax:minimum inhibitory concentration (MIC) ratio of 10 or greater for
      bacteria with an MIC of 2 microg/ml. CONCLUSION: Once-daily aminoglycoside dosing
      using the four nomograms resulted in inaccurate dosing, and because of the large
      variability in human pharmacokinetics, dosing nomograms such as these should be
      abandoned in favor of individualizing dosages with therapeutic drug monitoring.

PMID- 12222542
TI  - The effect of sepsis during parenteral nutrition on hepatic microsomal function
      in rats.
AB  - STUDY OBJECTIVE: To investigate the effect of sepsis during parenteral nutrition
      on hepatic cytochrome P450 (CYP) activity in rats. DESIGN: Prospective,
      randomized, controlled study. SETTING: University-based animal research
      laboratory. ANIMALS: Twenty adult male Sprague-Dawley rats. INTERVENTION: The
      animals were cannulated intravenously and randomized to receive parenteral
      nutrition (PN), intravenous live Escherichia coli 4 x 10(8) colony-forming
      units/100 g body weight for 2 consecutive days with PN (PNEC), or chow (CH).
      MEASUREMENTS AND MAIN RESULTS: Both PN alone and PNEC resulted in a progressive
      decline in hepatic CYP concentration compared with CH (0.53 +/- 0.10, 0.41 +/-
      0.17, and 0.35 +/- 0.14 nmol/mg microsomal protein, respectively, p < 0.05).
      Parenteral nutrition alone was associated with a 57% decrease in isoenzyme
      ethoxycoumarin-O-deethylase activity (ECOD) compared with CH, but sepsis did not
      further decrease ECOD activity any more than PN alone (0.103 +/- 0.049, 0.044 +/-
      0.018, and 0.050 +/- 0.020 nmol/mg microsomal protein/min, respectively, p <
      0.05). CONCLUSION: Hepatic CYP concentration declines with PN and is further
      decreased when compounded by sepsis. The disproportional decrease in ECOD
      activity relative to CYP concentration with PN is unchanged by sepsis, indicating
      a selective alteration in hepatic isoenzymes by PN.

PMID- 12222543
TI  - Risk of acute liver injury in patients with diabetes.
AB  - STUDY OBJECTIVES: To estimate the incidence of acute liver injury in patients
      with diabetes and compare it with the corresponding incidence in the general
      population, and to examine the association between occurrence of acute liver
      injury and administration of antidiabetic drugs in patients with diabetes.
      DESIGN: Retrospective cohort study. SETTING: United Kingdom General Practice
      Research Database. PATIENTS: A total of 34,328 patients with adult-onset (type 2)
      diabetes and a random sample of 50,000 patients with no recorded diagnosis of
      diabetes; all were aged 20-79 years from 1994-1998 and free of risk factors for
      hepatic disease. INTERVENTION: Using the United Kingdom General Practice Research
      Database as our resource, we followed the two cohorts to identify patients with a
      recorded diagnosis compatible with acute liver injury Medical records of all
      patients identified as potentially having liver injury were requested from the
      general practitioners to validate the diagnosis. MEASUREMENT AND MAIN RESULTS:
      After validation, 27 patients met our definition for having acute liver injury:
      14 in the diabetes cohort and 13 in the general population cohort. Overall annual
      incidence was 14.2 and 8.8/100,000 patient-years in the diabetes and general
      population cohorts, respectively. The adjusted relative risk of acute liver
      injury in the diabetes cohort compared with that of the general population cohort
      was 1.0 (95% confidence interval [CI] 0.2-3.7). Patients with diabetes taking
      antidiabetic drugs had a relative risk of 2.8 (95% CI 0.6-12.5) compared with
      those not taking these drugs. CONCLUSION: Our findings suggest that diabetes
      itself does not constitute a major risk for acute liver injury and that a small
      increased risk could be associated with use of antidiabetic drugs. However, due
      to the low number of cases detected, the estimates of risk with individual drugs
      are not conclusive.

PMID- 12222544
TI  - Differences in antimicrobial drug exposure in patients with various degrees of
      renal function based on recommendations from dosing references.
AB  - STUDY OBJECTIVE: To calculate and compare 24-hour area under the unbound drug
      concentration-time curves (AUC(0-24)) of antimicrobials with dosing
      recommendations from six commonly used dosing references. INTERVENTION: Unbound
      plasma concentration-time profiles of 13 antimicrobial agents (4 penicillins, 3
      cephalosporins, 2 carbapenems, aztreonam, 3 fluoroquinolones) were simulated at
      steady state using a one-compartment open model for a 70-kg adult based on
      pharmacokinetic parameters obtained from peer-reviewed literature. Simulations
      were performed at five levels of creatinine clearance (Cl(cr)). MEASUREMENTS AND
      MAIN RESULTS: Differences in AUC(0-24) for each antimicrobial agent were noted
      among the six references at each level of Cl(cr) as well as within references
      across the range of Cl(cr). In addition, up to 16-fold and 3-fold ranges in AUC(0
      24) values were observed for beta-lactams and fluoroquinolones, respectively, in
      one reference based on dosing recommendations at a single level of Cl(cr) (due to
      more than one dose and/or dosing interval). CONCLUSION: Clinicians should be
      aware of differences among common references when selecting dosages of
      antimicrobial agents, especially for patients with moderate-to-severe renal
      impairment.

PMID- 12222545
TI  - Comparison of two needle sizes for subcutaneous administration of enoxaparin:
      effects on size of hematomas and pain on injection.
AB  - STUDY OBJECTIVE: To determine whether use of a smaller needle size for
      subcutaneous injection of enoxaparin would reduce the size of injection-site
      hematomas and/or decrease the pain of injection. DESIGN: Prospective, randomized
      trial. SETTING: Community hospital in North Vancouver, British Columbia, Canada.
      PATIENTS: One hundred twenty-four patients with unstable angina or non-Q-wave
      myocardial infarction who were administered enoxaparin for anticoagulation.
      INTERVENTION: Each patient was randomly assigned to one of two groups. One group
      received enoxaparin injections with a 30-gauge, 5/16-inch insulin syringe, and
      the other group was injected with a 26-gauge, 3/8-inch tuberculin syringe.
      MEASUREMENTS AND MAIN RESULTS: Participating nurses used standard measuring tape
      to determine the largest diameter of each hematoma. Pain was assessed with a 10
      unit numeric scale. The two groups did not differ significantly with regard to
      either the mean size of the largest hematoma/patient (4.2 cm in the insulin
      syringe group vs 3.8 cm in the tuberculin-syringe group, p=0.68) or the mean pain
      score (0.3 in the insulin-syringe group vs 0.5 in the tuberculin-syringe group,
      p=0.10). CONCLUSIONS: Use of a 30-gauge, 5/16-inch insulin syringe instead of a
      26-gauge, 3/8-inch tuberculin syringe does not significantly reduce either
      hematoma size or pain of injection. A larger study is required to determine
      whether needle size affects the frequency of hematoma formation.

PMID- 12222546
TI  - Daily dosing versus alternate-day dosing of simvastatin in patients with
      hypercholesterolemia.
AB  - STUDY OBJECTIVE: To compare the efficacy of daily simvastatin administration with
      that of alternate-day therapy at double the daily dose. DESIGN: Nonrandomized,
      before-after comparison trial. SETTING: Outpatient clinic of a Veterans Affairs
      medical center. PATIENTS: Fifteen men with hyperlipidemia. INTERVENTION: The
      simvastatin regimen for patients with a low-density lipoprotein cholesterol (LDL)
      level at their established National Cholesterol Education Program goal was
      converted from daily dosing to double the daily dose given every other day for 8
      weeks. MEASUREMENTS AND MAIN RESULTS: Baseline laboratory values were obtained
      for patients receiving daily simvastatin therapy After 8 weeks of alternate-day
      therapy, follow-up laboratory values were obtained and assessed for efficacy and
      toxicity. The LDL-lowering effect of the daily dosing regimen was compared with
      that of the alternate-day dosing regimen. Paired t tests were computed to compare
      LDL concentrations before and after the study using a 95% confidence interval. No
      statistically significant difference was observed. CONCLUSION: Alternate-day
      dosing of simvastatin may be an effective alternative to daily dosing.

PMID- 12222547
TI  - Fluticasone is associated with lower asthma-related costs than leukotriene
      modifiers in a real-world analysis.
AB  - STUDY OBJECTIVE: To compare the impact of fluticasone propionate versus three
      leukotriene modifiers-montelukast, zafirlukast, and zileuton-on the cost of
      asthma within a managed care organization. DESIGN: Retrospective quasi
      experimental comparison. SETTING: Managed care organization with approximately
      350,000 enrollees. PATIENTS: Three hundred forty-seven patients with asthma who
      received at least two prescriptions for either fluticasone or a leukotriene
      modifier. Patients receiving both fluticasone and a leukotriene modifier were
      excluded. MEASUREMENTS AND MAIN RESULTS: Multivariate analysis was used to
      compare total asthma-related costs between treatment groups. A significant
      difference in total asthma-related costs was found between patients receiving
      fluticasone (adjusted mean cost $511) compared with those receiving a leukotriene
      modifier ($1,092; p=0.0001). Other significant predictors of postindex asthma
      related costs were pre-index asthma-related costs, a severity adjustment score,
      and the diagnosis of chronic obstructive pulmonary disease. Patients taking a
      leukotriene modifier obtained more short-acting beta-agonists than patients
      receiving fluticasone (6.49 +/- 4.05 vs 4.30 +/- 3.41, p < 0.0001). A survival
      analysis of time to receive any additional controller therapy revealed that
      patients receiving fluticasone were significantly less likely to receive another
      controller than were those receiving a leukotriene modifier (p=0.0014).
      CONCLUSION: These results suggest that fluticasone is associated with lower
      asthma-related costs than leukotriene modifiers.

PMID- 12222548
TI  - Valganciclovir: A new oral alternative for cytomegalovirus retinitis in human
      immunodeficiency virus-seropositive individuals.
AB  - Oral valganciclovir recently was approved by the Food and Drug Administration for
      treatment of cytomegalovirus (CMV) retinitis. We performed MEDLINE (June 1998-May
      2002) and AIDSLINE (June 1998-December 2000) searches of available information on
      valganciclovir, and the drug's prescribing information was used to identify
      relevant articles. Additional studies, case reports, reviews, and abstracts were
      identified from references in the reviewed literature. Most of the information
      was obtained from abstracts or product labeling, since few trials have been
      published in the medical literature. Valganciclovir is a prodrug of ganciclovir
      and has been shown to have significantly higher oral absorption than ganciclovir
      capsules. One short-term study found valganciclovir to be as effective as
      intravenous ganciclovir in treating CMV retinitis. Recommended dosages for
      patients with normal renal function are valganciclovir 900 mg twice/day for
      induction and 900 mg once/day for maintenance. Side effects are similar to those
      of intravenous ganciclovir and require periodic monitoring of complete blood
      count and renal function. Given the need for lifelong therapy for CMV retinitis
      in some human immunodeficiency virus-positive patients, valganciclovir is a
      welcome alternative to long-term administration of intravenous antivirals.

PMID- 12222549
TI  - Formoterol therapy for chronic obstructive pulmonary disease: a review of the
      literature.
AB  - Numerous clinical trials have investigated the use of formoterol, a long-acting
      beta2-agonist, for the treatment of chronic obstructive pulmonary disease (COPD).
      Formoterol provides bronchodilation as rapidly as albuterol, yet its efficacy and
      duration of action are similar to those of salmeterol. It demonstrates better
      spirometric efficacy than either ipratropium or theophylline alone, and its
      efficacy improves when administered in combination with ipratropium. Formoterol
      improves patients' quality of life and has a good safety profile. It is better
      tolerated than theophylline and has a similar tolerability to albuterol,
      salmeterol, and ipratropium. In short, formoterol is a bronchodilator with rapid
      onset of action and prolonged duration of action with a favorable efficacy,
      safety, and tolerability profile when used in patients with COPD. It provides a
      valid therapeutic option in the pharmacologic treatment of this disease.

PMID- 12222550
TI  - Stress-dose corticosteroid therapy for sepsis and acute lung injury or acute
      respiratory distress syndrome in critically ill adults.
AB  - Sepsis and acute lung injury (ALI) or acute respiratory distress syndrome (ARDS)
      are associated with high mortality rates despite recent therapeutic advances.
      Both disease states involve uncontrolled host defense responses that lead to
      inflammation, endothelial damage, enhanced coagulation, diminished fibrinolysis
      and fibroproliferation to produce microthrombi, and relative adrenal
      insufficiency. Corticosteroids inhibit the host defense response and may offer an
      inexpensive therapeutic option. Results of several randomized, double-blind
      studies demonstrated no survival benefit and higher secondary infection rates
      when supraphysiologic doses of corticosteroids were administered for less than 24
      hours. Recently, the emphasis of research for corticosteroid therapy has involved
      adrenocortical replacement dosage regimens administered for several days to
      weeks, with doses corresponding to the stress level of the disease. Stress-dose
      therapy with hydrocortisone in patients with septic shock who require vasopressor
      support, especially if adrenal insufficiency is present, accelerates hemodynamic
      stability and reduces mortality. The frequency of gastrointestinal hemorrhage was
      higher with corticosteroid therapy than with placebo, but the occurrence of
      secondary infections was similar to that of placebo. The only randomized, double
      blind study that evaluated stress-dose methylprednisolone therapy for ARDS was
      terminated early after only 24 patients were enrolled because therapy with
      methylprednisolone was associated with enhanced survival despite higher secondary
      infection rates. A multicenter study investigating stress-dose methylprednisolone
      for ARDS is under way and should provide valuable information. Sufficient data
      support stress-dose hydrocortisone therapy for vasopressor-dependent septic
      shock. Stress-dose methylprednisolone therapy for ALI-ARDS requires further study
      but may be warranted in cases of refractory infection-induced ARDS when impending
      mortality is likely.

PMID- 12222551
TI  - A review of methotrexate-induced accelerated nodulosis.
AB  - OBJECTIVE: To review the English-language literature on methotrexate-induced
      accelerated nodulosis, compile case reports of its occurrences, and make
      recommendations on the clinical management of patients. METHODS: A comprehensive
      search of MEDLINE, TOXLINE, and EMBASE databases was performed, along with a
      bibliographic search of key articles. Case reports were compiled separately. The
      Naranjo adverse drug reaction probability scale was used to assess causality.
      RESULTS: Twenty-seven case reports of patients with methotrexate-induced
      accelerated nodulosis were identified along with one series of 10 patients and
      one series of 21 patients. Probability assessment for most of the case reports
      was weak and left room for doubt regarding causality. Most patients were older
      than 50 years, were positive for rheumatoid factor, and had nodules on their
      fingers but did not have concurrent vasculitis. Some unusual sites of nodulosis
      were the larynx, lungs, Achilles tendon, and heart. Of 19 patients given
      hydroxychloroquine, colchicine, sulfasalazine, azathioprine, or D-penicillamine,
      all except two showed regression of the nodules; the response was unknown for one
      patient. CONCLUSION: Controversy surrounds the management of patients who develop
      accelerated nodulosis while receiving methotrexate therapy for rheumatoid
      arthritis. Our review of these data does not allow definitive conclusions because
      the available case reports and clinical trials are fragmented and incomplete.

PMID- 12222552
TI  - Development and validation of a survey to assess barriers to drug use in patients
      with chronic heart failure.
AB  - Scot H. Simpson, Pharm.D., M.Sc., Jeffrey A. Johnson, Ph.D., Karen B. Farris,
      Ph.D., and Ross T. Tsuyuki, Pharm.D., M.Sc. Objective. To report the development
      of and initial experience with a survey designed to assess patient-perceived
      barriers to drug use in ambulatory patients with heart failure. Methods. The
      Barriers to Medication Use (BMU) survey, developed from previous qualitative work
      by our group, was administered to 128 consecutive patients attending an
      outpatient heart failure clinic. The first 42 patients to return the survey were
      mailed a second survey to evaluate response stability over time. The survey
      contained 31 questions in five barrier domains (knowledge, previous drug therapy
      experiences, social support, communication, and relationship with health care
      professionals). Patients also completed the Minnesota Living with Heart Failure
      (MLHF) questionnaire and a self-reported drug use scale. Frequency of drug
      refills was used to estimate adherence. Reliability and construct validity of the
      BMU survey were assessed using correlation coefficients. Results. Response rates
      were 89% and 93% for the first and retest surveys, respectively The BMU survey
      showed modest internal consistency in the overall survey and in two of the five
      barrier domains. Responses to the first and retest surveys showed good stability
      over time in the overall survey and in four of the five barrier domains. Patients
      with good adherence reported few barriers; however, the association was not
      strong (Pearson correlation coefficient r = -0.14, p=0.14). Patients who reported
      few barriers also reported better MLHF scores (r = 0.42, p < 0.001), with the
      strongest association in the social support domain (r = 0.53; p < 0.001). All
      respondents reported having a good relationship with health care professionals.
      The most common barriers to drug use were poor support networks and previous
      adverse reactions. Conclusion. The BMU survey demonstrated reasonable reliability
      and validity characteristics in this first clinical experience. Despite high
      adherence, patients still reported barriers that may hinder optimal drug use.

PMID- 12222553
TI  - Angiotensin II receptor blocker-associated angioedema: on the heels of ACE
      inhibitor angioedema.
AB  - Angioedema and cough are known side effects of angiotensin-converting enzyme
      (ACE) inhibitors. Angiotensin-converting enzyme is a potent inhibitor of kinase
      II, which facilitates the breakdown of bradykinin. An increase in bradykinin
      levels results in continued prostaglandin E2 synthesis, vasodilation, increased
      vascular permeability, and increased interstitial fluid. In contrast, the
      angiotensin II receptor blockers (ARBs) do not increase bradykinin levels.
      Angioedema as a complication of ACE inhibitor therapy is not widely recognized;
      this complication is even less recognized with second-line ARBs. We report
      angioedema associated with losartan (an ARB) in a patient who had experienced
      angioedema secondary to enalapril (an ACE inhibitor). Almost half of patients
      with ARB-associated angioedema also had developed angioedema while receiving ACE
      inhibitor therapy. Clinicians should exercise caution when using ARBs in patients
      with a history of angioedema secondary to ACE inhibitors.

PMID- 12222554
TI  - Angioedema associated with candesartan.
AB  - Most large clinical trials report that the frequency of angioedema caused by
      angiotensin-converting enzyme (ACE) inhibitors is 0.1-0.2%. The most common
      theory for this rare but potentially fatal adverse drug reaction cites ACE
      inhibitor-mediated accumulation of bradykinin as the culprit. Because angiotensin
      II receptor blockers (ARBs) do not exert their effects on ACE, they are not
      expected to cause bradykinin accumulation and therefore angioedema. Recently,
      several cases of angioedema related to the administration of ARBs have been
      documented in the literature. The existence of ARB-induced angioedema suggests
      that additional or alternate mechanisms not involving bradykinin are present in
      drug-induced angioedema. While taking candesartan for hypertension, a 53-year-old
      woman with known ACE inhibitor intolerance developed angioedema. During her
      hospitalization, candesartan was stopped and immunosuppressive therapy was
      administered. Within 24 hours, the angioedema had resolved completely and the
      patient was discharged. In light of the recent literature on ARB-induced
      angioedema, ACE inhibitor-intolerant patients who begin ARB therapy should
      receive appropriate counseling and be monitored closely for this adverse
      reaction.

PMID- 12222555
TI  - Lactobacillus species as a cause of ventilator-associated pneumonia in a
      critically ill trauma patient.
AB  - Lactobacillus species are ubiquitous inhabitants of the human gastrointestinal
      and genitourinary tracts and rarely cause infections. Pneumonia caused by
      Lactobacillus has been reported only in immunocompromised patients and in one
      patient with structural lung disease. A 39-year-old, immunocompetent, critically
      ill woman developed ventilator-associated pneumonia, which was found to be caused
      by Lactobacillus. To our knowledge, this is the first such report. The infection
      was treated successfully with 14 days of intravenous vancomycin. Based on this
      case, Lactobacillus should be considered a possible cause of ventilator
      associated pneumonia in immunocompetent, critically ill patients.

PMID- 12222556
TI  - Methotrexate-induced toxic leukoencephalopathy.
AB  - Drug-induced leukoencephalopathy is a devastating adverse event that can cause
      significant morbidity and mortality. Risk factors include advanced age,
      administration of certain chemotherapies, presence of an Ommaya device, central
      nervous system malignancy, and most important, exposure to cranial radiation. A
      73-year-old woman developed leukoencephalopathy 2 months after her last dose of
      intraventricular methotrexate. Although leukoencephalopathy is a severe adverse
      effect of the agent, her case is different because it occurred without prior
      exposure to cranial radiation.

PMID- 12222557
TI  - Fentanyl-associated syndrome of inappropriate antidiuretic hormone secretion.
AB  - A 43-year-old woman with advanced pulmonary blastoma was admitted for worsening
      back pain. Her drug regimen included hydromorphone and benazepril. On admission,
      hydromorphone patient-controlled analgesia (PCA) was started for acute pain
      control and dexamethasone for possible cord compression. Baseline laboratory
      tests were unremarkable, but magnetic resonance imaging revealed T3 and L3
      lesions. Irradiation was started with improvement in her pain. In anticipation of
      discharge, a fentanyl transdermal patch was given, and PCA was tapered. Two days
      later, the patient became progressively confused and fell. Neurologic examination
      and computed brain tomography were normal. Her serum sodium was 119 mEq/L (normal
      136-144 mEq/L) and was confirmed on repeat testing, urine sodium was 194 mEq/L,
      and urine and serum osmolalities were 554 mOsm/kg (normal 300-900 mOsm/kg) and
      245 mOsm/kg (normal 280-300 mOsm/kg), respectively, consistent with the syndrome
      of inappropriate antidiuretic hormone secretion (SIADH). Fluids were restricted,
      hydromorphone PCA was started again, and fentanyl was discontinued. After 36
      hours, her serum sodium increased to 136 mEq/L. Because we were unsure whether
      the fentanyl or her cancer was causative and were unable to find any published
      reports of fentanyl-associated SIADH, we readministered the fentanyl patch 2 days
      later. Within 48 hours, serum sodium dropped to 123 mEq/L. Fentanyl was
      discontinued, fluids were restricted, and 3% saline was started. Her serum sodium
      increased to 132 mEq/L in 48 hours. The patient was prescribed oral hydromorphone
      and benazepril and was discharged. The repeated temporal relationship between the
      administration of fentanyl and the onset of SIADH strongly implicates fentanyl as
      the causative agent in this case. To our knowledge, this is the first report of
      fentanyl-associated SIADH.

PMID- 12222558
TI  - Toxic epidermal necrolysis after celecoxib therapy.
AB  - Toxic epidermal necrolysis (TEN) is a rare disease that is defined by extensive
      detachment of full-thickness epidermis. It most often is related to an adverse
      drug reaction. The drugs implicated in most cases of TEN have been sulfonamides,
      anticonvulsants, allopurinol, and some of the conventional nonsteroidal
      antiinflammatory agents. We describe a patient who developed a generalized
      desquamating rash after therapy with celecoxib.

PMID- 12222559
TI  - Bradycardia associated with intravenous methadone administered for sedation in a
      patient with acute respiratory distress syndrome.
AB  - The use of low tidal volumes with permissive hypercapnia in patients with acute
      respiratory distress syndrome may require heavy sedation to allow them to
      tolerate mechanical ventilation. Administration of methadone for sedation is an
      alternative to using other opioids, given its longer elimination half-life and
      incomplete cross-tolerance with other mu-receptor-active opioids. Methadone
      appears to have a molecular structure similar to that of verapamil, a calcium
      channel blocker, and may exhibit similar cardiac properties as well. A 43-year
      old man with acute respiratory distress syndrome experienced bradycardia while
      receiving a continuous infusion of methadone for sedation and mechanical
      ventilation management. This case report demonstrates that caution is warranted
      when high dosages of methadone are administered because of its potential cardiac
      effects.

PMID- 12222560
TI  - Recurrent peripheral arterial thrombosis induced by cisplatin and etoposide.
AB  - A 64-year-old woman receiving intravenous chemotherapy for stage IIIB non-small
      cell lung cancer experienced acute arterial thrombosis of the distal radial and
      entire ulnar arteries with subsequent arterial occlusion of the right popliteal
      artery. Two separate arterial occlusions occurred after administration of
      cisplatin and etoposide chemotherapy; the second occlusion occurred after
      rechallenge with the second cycle of chemotherapy. Although venous thrombosis is
      more common in patients with cancer than in the general population, chemotherapy
      induced arterial thrombosis rarely has been reported. To our knowledge,
      peripheral arterial occlusion after the first and second cycles of platinum-based
      chemotherapy has not been reported in the literature.

PMID- 12222561
TI  - The overselling of hormone replacement therapy.

PMID- 12222563
TI  - Most valuable preventive services don't reach targeted populations.

PMID- 12222564
TI  - Quality, patient safety recognized in incentive plans, survey finds.

PMID- 12222562
TI  - Developmental expression and tissue distribution of the lethal (2) giant larvae
      protein of Drosophila melanogaster.
AB  - Recessive mutations in the Drosophila tumor gene lethal (2) giant larvae affect
      the growth and tissue specificity of determined cells in imaginal discs and
      presumptive optic centers of the brain. To analyse the function of the l (2) gl
      gene during development, we have raised monoclonal antibodies against the l (2)
      gl protein. These antibodies detect a 130-kd protein in wild-type tissue which is
      absent in homozygous mutant tissues. The protein is detected in increasing
      amounts up to mid-embryonic stages. Antibody binding to embryo sections and
      indirect immunofluorescence labeling indicate that the protein is localized at
      the cellular membranes or in the intercellular matrix of the embryonic cells. The
      primordia of all larval tissues are labeled in the embryo. Much less labeling is
      found in the neural primordia of the central nervous system, except that within
      the supraoesophageal ganglion the regions of the presumptive optic centers are
      distinctly labeled. Moreover, the axon bundles of the ventral cord are labeled in
      the embryo, apparently a reflection of the accumulation of cell membranes here.
      After embryogenesis the l (2) gl protein is found at a low level until the end of
      the 3rd larval instar, when it is preferentially seen in the brain and imaginal
      discs. The protein distribution in embryonic and larval tissues correlates with
      already known proliferation patterns, which could indicate that the l (2) gl
      protein is involved in proliferation arrest of cells.

PMID- 12222565
TI  - Physicians should increase knowledge of herbal remedies.

PMID- 12222566
TI  - Attention to care of the dying brings recognition.

PMID- 12222567
TI  - [Recent advances in multi-variate and multi-dimensional analysis of heart rate
      variability and blood pressure variability].
AB  - Heart rate variability (HRV) and blood pressure variability (BPV) reflect the
      modulation activity of autonomic nervous system on cardiovascular function. There
      have been important advances in multi-variate, multi-dimensional and dynamic
      analysis of HRV and BPV during recent years. Modern signal processing methods,
      such as multi-variate system identification, time-frequency analysis and
      nonlinear dynamics analysis, could be adopted in the risk prediction, severity
      evaluation and therapeutic treatment assessment of cardiovascular diseases. These
      new methods might also be useful in special environmental medicine.

PMID- 12222568
TI  - [Change of cerebral blood flow velocity during 4 d head-down tilt bed rest].
AB  - Objective. To investigate the change of cerebral blood flow velocity during 4 d
      head-down tilt (HDT) bed rest in humans. Method. Eight healthy male volunteers
      were exposed to -6 degrees HDT bed rest for 4 d. Orthostatic tolerance was
      assessed by means of standard tilt test. Cerebral blood flow velocity in the
      right middle cerebral artery was measured by transcranial Doppler sonography
      before HDT (supine), on days 1, 3 and 4 of HDT and on day 2 post HDT. Result.
      After 4 d HDT, the frequency of orthostatic intolerance was significantly higher
      than those before HDT (P<0.05). The systolic, diastolic and mean blood velocities
      in the middle cerebral artery tended to decrease on days 1 and 3 of HDT, and
      decreased significantly on day 4 of HDT, compared with pre-HDT, and returned to
      basal levels on day 2 post HDT. The mean arterial blood pressure and diastolic
      blood pressure increased significantly, while the body weight decreased
      significantly during HDT. Conclusion. It is suggested that 4 d HDT may decrease
      cerebral blood flow velocity and increase the frequency of orthostatic
      intolerance. This decrease of cerebral blood flow velocity may be partially
      responsible for the increased risk of orthostatic intolerance.

PMID- 12222569
TI  - [Body temperature changes during 7 d -6 degrees head-down bed rest].
AB  - Objective. To investigate body temperature changes in man during 7-day -6 degrees
      head-down bed rest (BR). Method. Body temperatures were measured in the morning
      (6:00), afternoon (16:00) and evening (20:00) during 7 d BR in 18 healthy males
      (18-22 years old). Result. Rectal temperature (Tre) in the morning gradually
      decreased as time (d) of BR increased: after the 4th day of BR (BR4d), Tre
      significantly reduced compared with the supine control (SC, 36.50 +/- 0.03
      degrees C) before BR, and it consistently declined to 36.38 +/- 0.04 degrees C on
      BR7d; But Tre significantly increased in the afternoon after BR5d and in the
      evening after BR1d, with the final increments of 0.12 +/- 0.05 degrees C and 0.25
      +/- 0.03 degrees C respectively on BR7d. Mean body temperature (Tsk) in the
      morning was significantly higher from BR2d than its SC, with a final net increase
      (delta Tsk) of 0.38 +/- 0.14 degrees C on BR7d. And Tsk significantly increased
      in the afternoon and evening from BR4d, BR2d respectively. Skin temperature on
      the forehead (Tforehead) elevated in the morning during BR. While in the
      afternoon and evening, Tforehead were significantly higher from BR7d and BR6d
      than their SC. Conclusion. Both the difference in time of recording at a BR day
      and the time (d) of BR have significant influence on Tre, Tsk , and Tforehead
      (P<0.01). These data suggest that body temperature rhythm, body fluid loss and
      headward distribution, hypokinesis etc. induced by BR have an impact on human
      thermal regulation during BR.

PMID- 12222570
TI  - [Changes of human cerebral blood flow velocity and blood oxygen saturation under
      lower body negative pressure in upright seated position].
AB  - Objective. To investigate the effect of lower body negative pressure (LBNP) in
      upright seated position on cerebral blood flow velocity, heart rate (HR), and
      blood oxygen saturation (SaO2) in human. Method. Fifteen young men were selected
      as subjects. Blood flow velocity in middle cerebral artery (VMCA), HR and SaO2
      were measured at 0.5, 1, 2, 3, 4, and 5 min during LBNP and 1, 3, 5 min after 
      4.00 kPa and -6.67 kPa LBNP in upright seated position respectively. Result.
      Under -4.00 kPa LBNP, VMCA slowed down at 4, 5 min during LBNP (P<0.05), and HR
      speeded up at 3, 4, 5 min during LBNP (P<0.05). There were no significant changes
      of SaO2. Under -6.67 kPa LBNP, VMCA became slow at 2, 3 min (P<0.05), and at 4
      and 5 min (P<0.01) during LBNP. At 1 min after release of LBNP, VMCA did not
      recover, after which it recovered to control level. HR significantly increased
      (P<0.01) and SaO2 decreased at 5 min (P<0.05) during LBNP. Conclusion. LBNP can
      cause blood pooling in lower body so that VMCA and brain blood volume decrease.
      Then it causes loss of consciousness. The results of this experiment may provide
      experimental data for diagnosis of flight syncope and orthostatic intolerance.

PMID- 12222571
TI  - [Effects of simulated weightlessness on EEG frequency fluctuation
      characteristics].
AB  - Objective. To develop a method of EEG monitoring under special environment, which
      is of value for astronauts selection and training. Method. Weightlessness was
      simulated by means of -6 degrees head down bed rest (HDBR). Rest EEG was recorded
      in 12 male subjects (aged 18-22) with eyes-closed and then analyzed by means of
      EEG frequency-fluctuation analysis system. Result. Before HDBR, the dominant
      order at parietal and occiput was 10, 9, 11 Hz; At frontal and temporal regions 9
      Hz competed with 10 Hz for the main dominant component, while the third was 7 Hz.
      During HDBR, reversible changes of position and interrelation between 7, 8, 9,
      10, 11 and 12 Hz appeared, and the frequency components and their regions
      involved spread gradually. The probability of 7 Hz and 8 Hz dominance increased,
      while 10 Hz and 11 Hz dominance decreased. At parietal, occiput and post-temporal
      regions, 9 Hz competed with 10 Hz for the main dominant component, the third was
      7 Hz. At frontal and pre-temporal regions, 9 Hz occupied the main dominant
      position, while the second was 7 Hz (at right-frontal regions, it even occupied
      the main dominant position), the third was 10 Hz. Conclusion. Simulated
      weightlessness cause change of EEG dominant-frequency fluctuation competitive
      structure significantly. Brain adaptation function decrease, and headache can be
      easily induced. There exists a potential influence on brain function.

PMID- 12222572
TI  - [Changes of serum alkaline phosphatase and electrolytes during 21 d head down bed
      rest].
AB  - Objective. To investigate the effect of simulated weightlessness on serum
      alkaline phosphatase (ALP), calcium, magnesium, chlorine and phosphorus. Method.
      6 healthy males, aged 24.8 +/- 6.1, were exposed to -6 degrees HDT bed rest for
      21 d. Activity of serum alkaline phosphatase, serum contents of calcium (Ca),
      magnesium (Mg), chlorine (Cl) and phosphorus (P) ions were assayed before HDT (d
      3), on the 3rd, 10th and 21st day during HDT and after HDT (d+2). Ca was measured
      by methyl thymol blue method, P was determined with ultraviolet
      spectrophotography, determination of Mg and Cl were made with enzyme method, ALP
      was examined with 4-nitrobenzene phosphate method. Result. Serum Ca2+ levels were
      significantly higher at d10, d2l and d+2 than the value of d-3 (P<0.01). P3+
      levels declined significantly on d2l as compared with d-3 (P<0.01). During the
      HDT and after HDT, Mg2+ declined to a level below that before HDT (P<0.05 or
      P<0.01). Cl- were significantly higher at d2l and d+2 than the value of d-3
      (P<0.01). ALP level was higher on d2l than on d-3 (P<0.01). Conclusion. 21 d HDT
      induced increase of Ca, Cl, ALP, and decline of Mg and P. The changes may reflect
      the imbalance of metabolism.

PMID- 12222573
TI  - [Effects of 21 d -6 degrees bed rest on diastolic function of human left
      ventricle].
AB  - Objective. To investigate the effects of head down bed rest (HDBR), the simulated
      weightlessness, on the diastolic function of human left ventricle, and to discuss
      its role in cardiovascular deconditioning after space flight. Method. Six healthy
      young volunteers were subjected to -6 degrees HDBR for 21 d. Ultrasound Doppler
      technique was used to examine the changes of the diastolic function before, on
      the 10th, and 21st day during and 2nd day after HDBR. The orthostatic tolerance
      was also tested before and after HDBR. Result. Peak E-wave velocity (PEV) , peak
      A-wave velocity (PAV) , and velocity total integration of E-wave (VTI E), were
      significantly decreased (P<0.05) on the 10th and 21st day during and the 2nd day
      after HDBR, and velocity, total integration of A-wave (VTI A), ratio of E/A, and
      ratio of VTI E/A were also decreased, but did not reach the significant level
      (P>0.05). None of the six subjects passed the orthostatic tolerance test after
      HDBR. Conclusion. Simulated weightlessness can induce marked decline in diastolic
      function of human left ventricle.

PMID- 12222574
TI  - [Effects of head down bed rest or drinking water containing electrolytic silver
      ion on intestinal bifidobacteria].
AB  - Objective. To investigate the effect of head down bed rest (HDBR) or electrolytic
      silver-ion on intestinal bifidobacteria in men and mice. Method. Three tests were
      conducted. Counts of bifidobacteria in feces were made in: 1) 5 male healthy
      volunteers after 21 d -6 degrees HDBR. 2) 4 groups of mice drank water containing
      no Ag+, 0.20, 0.40 and 0.60 mg/ L of Ag+ respectively for 1 month. 3) Seven male
      healthy volunteers drank water containing 0.20 mg/L of silver-ion for 16 days.
      Result. 1) The count of bifidobacteria after HDBR [8.08 +/- 0.82 (lgn/g)] was
      significantly decreased as compared with the control group [8.72 +/- 0.82
      (lgn/g)] (P<0.01). It suggests that HDT -6 degrees bed-rest might reduce the
      number of bifidobacteria in the human colon. 2) The count of bifidobacteria in
      feces was negatively correlated with the silver-ion concentration in the water
      (r= -0.992, P<0.01). 3) The count of bifidobacteria in feces after test [7.83 +/-
      0.71(lgn/g)] was significantly decreased as compared with that before the test
      (8.91 +/- 0.84) (P<0.05). Conclusion. It demonstrates that HDT -6 degrees bed
      rest and electrolytic silver-ion all might reduce the count of bifidobacteria in
      feces.

PMID- 12222575
TI  - [N2 effect on non-target event-related brain potentials during auditory selective
      response task].
AB  - Objective. To study N2 effect and its feature on non-target event-related brain
      potentials during auditory selective attention. Method. The subjects were 16
      healthy right-handed male volunteers aged 23.2 +/- 2.1 years. The stimuli were
      male voice of one-digit numbers (2 to 7), which were single syllable pronunciated
      in Chinese, and appeared randomly with equal probability. The subjects were asked
      to press a switch as soon as the target signal (odd or even number) was heard but
      make no response to the non-target signal. EEG signals at 9 locations were
      recorded. Result. 1) A negative component N280 (N2 effect) was found after non
      target stimuli as compared to target stimuli, which was significant in the
      frontal brain locations; 2) P3 was smaller and its peak appeared later in non
      target ERPs than in target ERPs. Conclusion. N2 effect was also elicited by non
      target stimuli during auditory modality. We assume that N2 effect might reflect
      the readjusting of model stored in working memory at the frontal brain.

PMID- 12222576
TI  - [The mechanism of gain in scale of visual attention].
AB  - Objective. To compare the cortical mechanisms associated with the visual spatial
      attention directed by fixed location cues. Method. The subjects were 12 healthy
      right-handed young volunteers. The visual stimuli were presented with the
      sequence as: background-cue-target. The cue was a black circle varied in three
      different sizes randomly. The foci of the circles were always at the center of
      the screen. The task of the subjects was to search the target within the cue
      circle and discriminate its orientation. Electroencephalogram (EEG) was recorded
      from 128 scalp sites. Result. The reaction time (RT) to the targets in the same
      location shortened when the cue size enlarged. The target evoked P1 and N1
      components were not affected by the attentive region size, while the amplitudes
      of the inferoposterior P2 and anterosuperior N2 enlarged when the attentive
      region size enlarged. Conclusion. 1) The P1 and N1 components under visual
      attention were related to the spatial location processes mainly. 2) Cue-evoked P2
      and N2 components were related to the size of attentive region. 3) The processes
      of spatial location information were earlier than attentive scale information,
      which supported the theory that spatial selection is a prerequisite for correct
      processes of visual object information.

PMID- 12222577
TI  - [Effects of fast decompression on prostaglandins content in cerebral tissue of
      guinea pigs].
AB  - Objective. To investigate the effect of fast decompression on prostaglandins in
      cerebral tissue. Method. 26 guinea pigs were divided into 2 groups randomly. The
      animals in group FDC (group 1) were treated with fast decompression and formed
      decompression sickness, but those in control group (group 2) were not treated
      with decompression. The contents of prostaglandin E2 (PGE2), 6-keto-prostaglandin
      F1a (6-K-PGF1a) and thromboxane B2 (TXB2) in cerebral tissue of the animals were
      determined by enzyme immunoassay. Result. The content of PGE2 in cerebral tissue
      of FDC animals was twice as much as that in control animals. The content of TXB2
      in cerebral tissue of FDC animals was 3 times as high as that in control animals,
      and that of 6-K-PGF1a in cerebral tissue of FDC animals was 2.6 times as that in
      control animals. It showed very significant differences as compared with control
      group (P<0.01). Conclusion. The content of PGs in cerebral tissue increased
      markedly after fast decompression, and may cause cerebral injury.

PMID- 12222578
TI  - [On physique of astronauts as viewed from the point of Traditional Chinese
      Medicine].
AB  - Good health physique and fine psychological quality are required for an
      astronaut. Selection and health care of foreign astronauts are based on western
      medicine principles. In order to initiate space medicine with a new feature of
      Chinese Medicine. It needs further discussion on the application of Traditional
      Chinese Medicine to the research and practice of space medical science.

PMID- 12222579
TI  - [Changes of cardiac kinetics during various stages of space flight].
AB  - Arterial blood pressure is dependent on ordinary cardiac function in human
      beings. Cardiac kinetics serves as important cardiovascular parameters during
      various stages of space activities. Although the reports about cardiac kinetics
      were not always in consistency during spaceflight, obvious changes during
      orthostatic stress after spaceflight were commonly observed. The mechanisms of
      orthostatic intolerance after spaceflight remain to be clarified, and the effects
      of changes of cardiac kinetics remain to be discussed. This paper briefly reviews
      the reports on cardiac kinetics during various stages of space activities and the
      researches on the mechanism of orthostatic intolerance after spaceflight.

PMID- 12222580
TI  - [Application of lower body negative pressure (LBNP) in aerospace medicine].
AB  - Effects of LBNP is similar to that produced by gravitational force, especially as
      a stress factor on the cardiovascular system as has been concerned in the area of
      aerospace medicine. This paper described experimental equipment, methods and
      physiological effects of LBNP, especially its application in the area of
      aerospace medicine. Several aspects for future research were put forward.

PMID- 12222581
TI  - [Research progress in space plant breeding].
AB  - A brief introduction of the advances in study of space mutation of plants is
      given in this article. It includes: factors influencing plants in space flight,
      different levels of biological effects of space mutation and researches on space
      mutation breeding. Prospects are also put forward in this article.

PMID- 12222582
TI  - Managing anemia in patients with chronic kidney disease or cancer: development
      and role of darbepoetin alfa.

PMID- 12222583
TI  - An overview of the pharmacokinetic disposition of darbepoetin alfa.
AB  - Darbepoetin alfa is a new erythropoiesis-stimulating protein that has five
      carbohydrate chains compared with three in recombinant human erythropoietin (r
      HuEPO, epoetin alfa). Owing to its increased carbohydrate content, the terminal
      half-life of darbepoetin alfa is 2-3-fold greater than that of r-HuEPO in
      patients with chronic kidney disease or cancer. This pharmacokinetic property may
      allow for less frequent administration of darbepoetin alfa compared with r-HuEPO.
      Although several regimens are still being tested, a predictable increase was
      observed in serum concentrations of darbepoetin alfa and no clinically relevant
      accumulation was seen with once-weekly administration for up to 48 weeks.
      Preliminary data in patients with cancer suggest that concurrent chemotherapy may
      influence the pharmacokinetics of darbepoetin alfa. Therefore, the timing of
      dosing relative to chemotherapy may be important. Darbepoetin alfa, through its
      potential for less frequent dosing, offers a more convenient treatment option
      than r-HuEPO for patients with anemia secondary to cancer or kidney disease.

PMID- 12222584
TI  - Darbepoetin alfa, a new therapy for the management of anemia of chronic kidney
      disease.
AB  - Anemia of chronic kidney disease (CKD) results primarily from a deficiency of the
      hormone erythropoietin. Treatment of anemia in the early stages of CKD is
      essential to reduce the risk of developing anemia-associated complications and to
      improve health-related quality of life. Treatment with recombinant human
      erythropoietin (r-HuEPO, epoetin alfa) can correct erythropoietin deficiency and
      increase red blood cell production, but the short half-life of r-HuEPO
      necessitates frequent injections. Reducing the frequency of administration has
      potential benefits for both patients and health care providers. Darbepoetin alfa
      is a new erythropoietic protein with greater biologic activity and a longer
      dosing interval than those of r-HuEPO. It has been shown to be effective when
      administered once/week and once every 2, 3, or 4 weeks, and is well tolerated.
      With the ability to simplify anemia management by allowing less frequent dosing,
      darbepoetin alfa offers an effective alternative to r-HuEPO for the treatment of
      anemia of CKD.

PMID- 12222585
TI  - Overview of cancer-related anemia: focus on the potential role of darbepoetin
      alfa.
AB  - Cancer-associated anemia is common and has many causes, including the effects of
      the underlying disease and cancer treatment. The effect of anemia on patients
      with cancer was not appreciated fully until relatively recently. Several well
      designed studies have demonstrated the relationship between anemia and fatigue,
      and the effect of fatigue on quality of life. These data have resulted in a
      greater awareness of anemia in cancer and have increased the use of recombinant
      human erythropoietin (r-HuEPO, epoetin alfa) therapy for the treatment of anemia.
      Recombinant HuEPO produces a hemoglobin response in 50-60% of patients with
      cancer; however, to obtain this response rate, frequent dosing is required.
      Darbepoetin alfa, a recently developed erythropoietic protein, has a longer half
      life than that of r-HuEPO, enabling less frequent dosing, and has a greater in
      vivo activity. In studies of patients with cancer who develop anemia, darbepoetin
      alfa has proved to be well tolerated and effective, and its advantages make it a
      potential improved treatment option for anemia in these patients.

PMID- 12222586
TI  - Dose conversion from recombinant human erythropoietin to darbepoetin alfa:
      recommendations from clinical studies.
AB  - Recombinant human erythropoietin (r-HuEPO, epoetin alfa), is an established and
      effective treatment for anemia associated with both chronic kidney disease (CKD)
      and cancer and has improved the management of anemia over alternatives such as
      transfusion. Darbepoetin alfa is a new erythropoietic agent with a 3-fold longer
      half-life and increased in vivo potency relative to r-HuEPO. These properties
      allow patients to be treated with longer dosing intervals than with r-HuEPO.
      Relative potency between r-HuEPO and darbepoetin alfa is not a fixed relationship
      but is dependent on several factors. Clinical study results suggest that greater
      relative potency differences are seen between r-HuEPO and darbepoetin alfa when
      the dosing intervals are longer and when r-HuEPO dose requirements are higher.
      Although 200 U of r-HuEPO contains the same peptide mass as 1 microg of
      darbepoetin alfa, a fixed ratio of 200:1 does not necessarily predict an
      appropriate dose conversion between the two drugs across the entire spectrum of
      dose ranges. When converting patients with CKD from r-HuEPO to darbepoetin alfa,
      dosing should be based on relevant clinical data. Appropriate guidance for
      conversion of patients with CKD from r-HuEPO to darbepoetin alfa is provided in
      the approved United States package insert for darbepoetin alfa. In patients who
      are prescribed darbepoetin alfa, either by conversion from r-HuEPO or as de novo
      treatment, therapy should begin according to recommendations in the package
      insert, after which, doses should be titrated individually according to each
      patient's hemoglobin response. Dosing data from oncology clinical studies,
      although not necessarily applicable to CKD, indicate similar potency ratios
      between r-HuEPO and darbepoetin alfa, and in addition affirm the finding that, as
      the interval between doses of darbepoetin alfa is increased, hemoglobin response
      is maintained.

PMID- 12222587
TI  - Case markers as clause boundary inducers in Japanese.
AB  - The present paper provides evidence that the processing of verb final clauses
      proceeds incrementally based on local information that becomes available with
      each word. The results of three self-paced reading experiments are reported in
      support of the proposal that NPs in Japanese are associated within clauses before
      a verb is processed. It is argued that a clause boundary is posited whenever case
      markers prevent two NPs from being part of the same clause, and slow reading
      times at the second NP are used as supporting evidence. Moreover, clause
      boundaries induced by case narking can facilitate processing at later points in
      the sentence as attested to by faster reading times at relative-clause heads.
      Contrary to previous findings that argued against a subclass of head-driven
      parsers, the present results are not easily reconcilable with any type of model
      that delays parsing decisions until a verb is available in the input sentence.

PMID- 12222588
TI  - Levels of processing and phonological priming in Chinese character completion
      tests.
AB  - This study investigated the level of processing (LoP) effect in the Chinese
      character completion task. Stem cues, either graphemically or phonetically
      related to a target character, were used to generate two different kinds of
      perceptual tests. By giving participants either direct or indirect instructions,
      the character completion tests could be either an explicit or an implicit memory
      test. For the implicit test, LoP effects were not found between Read and
      Generation conditions, whereas the Physical conditioni did not produce priming.
      In addition, no priming was found when participants received graphemic cues
      during the test. For the explicit test, on the other hand, a standard pattern of
      LoP effects was found between the Physical, Read, and Generation conditions.
      Results are discussed in terms of the importance of lexical access for character
      completion tests and the role of phonology in processing Chinese characters.

PMID- 12222589
TI  - Practice effects on speech production planning: evidence from slips of the tongue
      in spontaneous vs. preplanned speech in Japanese.
AB  - The present study addresses the question of how practice in expressing the
      content to be conveyed in a specific situation influences speech production
      planning processes. A comparison of slips of the tongue in Japanese collected
      from spontaneous everyday conversation and those collectedfrom largely preplanned
      conversation in live-broadcast TV programs reveals that, although there are those
      aspects of speech production planning that are unaffected by practice, there are
      various practice effects, most of which can be explained in terms of
      automatization of the processing of content, resulting in shifts in the loci of
      errors.

PMID- 12222590
TI  - Conceptual clusters in figurative language production.
AB  - Although most prior research on figurative language examines comprehension,
      several recent studies on the production of such language have proved to be
      informative. One of the most noticeable traits of figurative language production
      is that it is produced at a somewhat random rate with occasional bursts of highly
      figurative speech (e.g., Corts & Pollio, 1999). The present article seeks to
      extend these findings by observing production during speech that involves a very
      high base rate of figurative language, making statistically defined bursts
      difficult to detect. In an analysis of three Baptist sermons, burst-like clusters
      of figurative language were identified. Further study indicated that these
      clusters largely involve a central root metaphor that represents the topic under
      consideration. An interaction of the coherence, along with a conceptual
      understanding of a topic and the relative importance of the topic to the purpose
      of the speech, is offered as the most likely explanation for the clustering of
      figurative language in natural speech.

PMID- 12222591
TI  - Rhythms of dialogue in infancy: comments on Jaffe, Beebe, Feldstein, Crown, and
      Jasnow (2001).
AB  - Analysis of coordinated interpersonal timing has become an important tool for the
      study of infant-adult, peer, and marital interactions. Past research suggests
      that social coordination is informative about the quality of the caregiver-child
      social relationship. Does infant experience of certain types of coordination and
      pattern in early social interactions with caregivers predict better cognitive and
      social developmental outcomes? The recent monograph "Rhythms of dialogue in
      infancy" (Jaffe, Beebe, Feldstein, Crown, & Jasnow, 2001) provides the strongest
      evidence to date that it does. Moderately coordinated social interactions in
      early infancy predicted the most favorable developmental outcomes, and degree of
      coordination was influenced by contextual factors such as setting and nature of
      the relationship between the infant and its social interaction partner. This
      study provides a model for future research in this area and points toward
      important questions for future research on infant-caregiver social interactions.

PMID- 12222592
TI  - Processing hyponymy in L1 and L2.
AB  - This study examined the processing of hyponmy in L1 and two levels of performance
      (overall and high proficiency) in L2 in a group of Persian-English bilinguals. In
      two experiments, the same participants detected semantic relation in hyponymy
      pairs (i.e., hyponym-superordinate vs. superordinate-hyponym) in L1 (experiment
      1) and L2 (experiment 2). The variables of pair type, stimulus onset asynchrony
      (SOA), language, and language proficiency were manipulated Overall, the results
      showed that participants median RTs and SDs were significantly greater in L2.
      This suggests that L2 processing in unbalanced bilinguals is less automatic than
      L1 processing. The findings of experiment 2 with the higher proficiency group
      showed a trend toward performance in L1 and therefore confirmed the prediction of
      the hierarchical model of bilingual memory that lexical processes in more-fluent
      bilinguals approximate those of L1 speakers. The results of the two experiments
      also showed that participants were significantly faster when presented with
      superordinate-hyponym word pairs than with hyponym-superordinate word pairs at
      100-ms SOA in both L1 and L2 conditions. The results at 200-ms SOA, however,
      showed an opposite trend, although the results with L2 did not reach
      significance. This trend of results points to a possibility of automatic vs.
      strategic processing in the sense that participants processing of hyponymy
      relation was more strategic than automatic at 200-ms SOA.

PMID- 12222593
TI  - Spotlight on etPEP.

PMID- 12222594
TI  - Diary of a veterinary volunteer in India.

PMID- 12222595
TI  - Antibiotic-resistant bacteria in chicken meat.

PMID- 12222597
TI  - References to some homoeopathic research.

PMID- 12222596
TI  - EAD response agreement--what does it mean for vets?

PMID- 12222598
TI  - Accurate citation of published work is necessary in this profession.

PMID- 12222599
TI  - Number and distribution of Australian veterinarians in 1981, 1991 and 2001.
AB  - OBJECTIVE: To analyse the number and distribution of the Australian veterinary
      work-force, and to assess changes in it that have occurred since 1981. PROCEDURE:
      The postcode and gender of each veterinarian who was registered, resident and
      apparently working in each state and territory in 1981, 1991 and 2001 was
      obtained from veterinary board lists, entered on an Excel data base, and analysed
      using the statistical program SAS System 7 for Windows 95. The Official
      Australian Postcode Map was used to determine the location of postcode areas, and
      publications of the Australian Bureau of Statistics provided data on human
      populations. RESULTS: At the end of June 2001, 6358 veterinarians were
      registered, resident and apparently working in a state or territory of Australia.
      This was 100% higher than in 1981. Over the intervening 20 years, the number had
      increased by 3181, 2001 of whom were female. Between 1981 and 1991 the increase
      in major cities was 898 and in rural areas 682, of whom 357 were male. Between
      1991 and 2001 the increase in cities was 1139 and rural areas 462, of whom only
      98 were male. The density of veterinarians in Australia - 330/million people - is
      higher than in the UK (213/million), USA (218/million) and Canada (250/million).
      CONCLUSIONS: The relative number of veterinarians in Australia is now higher than
      in the UK, USA and Canada, and is likely to continue to increase. There is
      evidence of maldistribution, with many rural practices facing shortages of
      veterinarians with the experience and inclination to maintain veterinary services
      over the longer term, and some cities likely to become overcrowded with
      veterinarians.

PMID- 12222600
TI  - Protothecal colitis in a German shepherd dog.
AB  - A 3 1/2-year-old intact male German Shepherd Dog was admitted with a history of
      protracted haemorrhagic diarrhoea and tenesmus. Clinical evaluation revealed
      thickening of the rectal mucosa and presence of fresh blood and mucus in the
      faeces. Severe mucosal granularity and multiple nodules, in addition to a rectal
      stricture 7 to 9 cm from the anus, were found on colonoscopy. Histopathological
      evaluation of biopsy specimens identified organisms with morphologic features
      compatible with those reported for Prototheca spp. Although surgical excision of
      the rectal stricture was performed and ketoconazole treatment was instituted
      postoperatively, the dog's clinical condition deteriorated and euthanasia was
      performed 4 months later.

PMID- 12222601
TI  - Metastatic sclerosing mesothelioma in a cow.
AB  - Metastatic sclerosing mesothelioma in a crossbred cow is described. Accumulation
      of fluid in the abdominal cavity and solitary or coalesced nodules on the
      peritoneum, hepatic capsule and visceral pleurae, were observed after slaughter.
      Histological examination of the nodules revealed that they were composed of
      tubular structures supported by massive connective tissue. The lumina of the
      tubules were lined by solitary neoplastic mesothelial cells, or occasionally
      small groups of such cells were observed in the lumen. Identification of the
      mesothelial character of the tumours was dependent upon the histopathological and
      cytological characteristics of the nodules and histochemical stainings.

PMID- 12222602
TI  - Suspected Nerium oleander (Oleander) poisoning in a horse.

PMID- 12222603
TI  - The squatters and the blowflies.
AB  - Cutaneous myiasis in Australian sheep became an increasing problem in the early
      years of the 20th century after the import of the wrinkly Vermont Merinos and the
      introduction of Lucillia cuprina. WE Abbott, a successful pastoralist in New
      South Wales at that time, wrote a little-known and unusual description of early
      methods of control: a parody based on an episode in Through the Looking Glass by
      Lewis Carroll. The plight of struck sheep and the lives and times of Abbott,
      several other pastoralists and the entomologists of the New South Wales
      Department of Agriculture are illuminated as the Walrus and the Carpenter walk
      again across the hills and pastures of New South Wales.

PMID- 12222604
TI  - Molecular characterisation of Victorian Newcastle disease virus isolates from
      1976 to 1999.
AB  - OBJECTIVE: To characterise Newcastle disease virus isolates obtained in Victoria
      from 1976 to 1999 and identify the diversity of FO cleavage signal. DESIGN: RT
      PCR using viral RNA extracted from positive NDV allantoic fluid was performed to
      amplify a segment of the NDV F and HN genes. Molecular characterisation of the
      nucleotide and amino acid sequences within the FO cleavage site was undertaken.
      RESULTS: All isolates contained 'avirulent FO cleavage signal sequence of varied
      amino acid composition. CONCLUSIONS: Molecular characterisation of past and
      present NDV FO cleavage signal sequences will provide valuable epidemiological
      information and assist in understanding the genetic origins and relationships of
      outbreaks.

PMID- 12222605
TI  - The epidemiology of subfertility in non-seasonal calving dairy herds in the
      Camden region of New South Wales: description of population and incidence.
AB  - OBJECTIVE: To describe biographic, reproductive, production and disease
      characteristics of 965 Holstein cows from 10 non-seasonal calving dairy herds in
      the Camden region of New South Wales, and to describe the incidence of
      subfertility, that is, conception requiring > 2 inseminations, in this
      population. DESIGN: A retrospective epidemiologic study. METHODS: Computer
      records were used to determine biographic, reproductive, production and disease
      characteristics in all lactations that commenced between 1 July 1995 and 30 June
      1996 and resulted in conception during that lactation. Differences in these
      characteristics among herds and between primiparous and multiparous cows were
      examined. The lactational incidence of subfertility for lactations commencing
      during the study period was determined. RESULTS: Ten herds with appropriate
      records and management structures entered the study. Herd size ranged from 86 to
      203 lactating cows. Nutritional and reproductive management of these herds was
      typical of smaller pasture-based herds within the study region. Records from 1320
      cows were available, of which 965 were considered suitable for descriptive
      analysis. Monthly variations in number of cows calving were noted, with number of
      lactations commenced by primiparous and multiparous cows peaking in January and
      October, respectively. Significant (P < 0.001) inter-herd differences for all
      reproductive, disease and milk production outcomes were detected for both the
      entire population and within primiparous and multiparous subgroups. Of 1041 cows
      submitted for insemination, 76 failed to conceive. The lactational incidence rate
      (LIR) of subfertility in all lactations was 21.1% (95% CI 19-24%). and among all
      cows conceiving was 22.8% (95% Cl 20-25%). The LIR of subfertility in primipara
      was 24.1% (95% Cl 19-28%) and varied widely between herds (10%-40%). The LIR of
      subfertility in multipara was 22.2% (95% Cl 20-25%) and also varied widely
      between herds (7%-46%). CONCLUSION: Parity and herd of origin should be
      considered in any further analyses of these data.

PMID- 12222606
TI  - The epidemiology of subfertility in non-seasonal calving dairy herds in the
      Camden region of New South Wales: preliminary investigation of risk factors.
AB  - OBJECTIVE: To investigate relationships between biographic, reproductive,
      production and disease traits and subfertility among 965 Holstein cows from 10
      non-seasonal calving dairy herds in the Camden region of New South Wales. DESIGN:
      A retrospective case-control study METHODS: Biographical, disease and
      reproductive data were collated from computerised records for cows with
      lactations that commenced between 1 July 1995 and 30 June 1996 and univariable
      and bivariable associations with subfertility were determined. RESULTS: Records
      from 965 cows that conceived were considered for risk factor analyses.
      Associations between subfertility and a number of risk factors (P < 0.3) were
      detected. Significant (P < 0.05) risk factors for subfertility in multiparous
      cows included herd of origin and, after controlling for the effect of herd,
      subfertility in the previous lactation, greater than 62 days dry, parity greater
      than five, interval between calving and first recorded heat, metritis and cystic
      ovarian disease. Herd of origin and, after controlling for herd effects,
      dystocia, metritis and percentage of milk fat plus protein at the time of first
      service were significant (P < 0.05) risk factors for subfertility in primiparous
      cows. The direction and magnitude of these associations are presented.
      CONCLUSION: Subfertility has a similar rate of occurrence in the herds examined
      to that reported overseas. Although herd of origin has a substantial effect on
      individual risk of subfertility, cow-level risk factors for subfertility are
      likely to exist. Exposures differ between primiparous and multiparous cows.

PMID- 12222607
TI  - Principles for the use of macrocyclic lactones to minimise selection for
      resistance.

PMID- 12222608
TI  - Emission impossible? The challenge of quantifying sources and releases of POPs
      into the environment.

PMID- 12222609
TI  - Characterisation of DNA probes for the analysis of metallothionein gene
      expression in the bank vole (Clethrionomys glareolus).
AB  - DNA probes have been developed for subsequent use in monitoring the exposure of
      animals to heavy metal pollution in terrestrial environments using
      metallothionein (MT) gene expression in the bank vole (Clethrionomys glareolus).
      Three different bank vole sequences were characterised corresponding to the cDNA
      and the genomic DNA for MT-I and the genomic DNA for MT-II. Nucleotide sequence
      analysis indicates that the coding sequences of the bank vole MT-I and MT-II
      genes exhibit a very high degree of similarity (greater than 92%) to the
      corresponding genes of the Chinese hamster, the mouse and the rat. In common with
      other mammalian MT genes, both the MT-I and MT-II genes in the bank vole are
      interrupted by two introns, which are at identical positions as those in other
      rodent MT genes; furthermore, the sizes of these introns are similar to those in
      other rodents with the first intron being larger than the second and those in the
      MT-I gene being larger than those in the MT-II gene. The predicted amino acid
      sequence for the proteins shows that both proteins contain 20 cysteine residues
      at positions identical to those in other known mammalian MTs. The availability of
      these DNA sequences now provides a good opportunity to investigate MT gene
      expression and possible gene amplification in bank voles exposed to metal
      pollution.

PMID- 12222610
TI  - Sr and Pb isotopes as environmental indicators in environmental studies.
AB  - An environmental indicator is a numerical or a descriptive categorization of
      environmental data with the primary purpose of assessing the affected
      environment. In these studies, two characteristic isotopes, namely Sr and Pb,
      were assessed of their ability to describe the affected environment in
      environmental studies by detecting trends of pollution over short as well as long
      time periods and by identifying sources of contamination. The ability of
      environmental indicators to serve as elements in summarizing the situation of the
      affected environment is discussed. An illustrative example is presented where
      lead isotopes are used to understand the source of pollution in Kozani, a small
      rural area in Greece. Conclusions are derived in terms of the source of the
      pollution in the specific area.

PMID- 12222611
TI  - Validity of detection of microbial growth in buildings by trained dogs.
AB  - Microbial growth in buildings may evoke respiratory and other symptoms in the
      occupants and promote decay of construction materials. The decay in wood is
      usually caused by dry-rot fungus, leading to the decomposition of cellulose and
      lignin. There are also some mold fungi and bacteria that can use wood as a
      nutrient. In this study, two trained dogs were used to detect microbial growth
      present in buildings. The rot fungi Serpula lacrymans, Coniophora puteana and
      Antrodia sinuosa were used in the training. In addition to decay samples, pieces
      of healthy birch, pine and imbued wood were used as controls. Another experiment
      was made using bacteria (Streptomyces sp.). In these experiments, a total of 100
      decay, 75 control and 25 bacteria samples were used. The dogs detected 75% of the
      decay and 60% of the bacteria samples. Some (0-24%) control samples were also
      expressed as positive. Since the dogs identified also the bacteria samples
      without any specific training, a new test with some mold strains (Cladosporium,
      Botrytis, Trichoderma, Penicillium, Aspergillus) was carried out. The dogs found
      all the decay, mold and bacteria samples but only one sample of healthy wood. The
      use of dogs to detect mold or decay damage appears to have high specificity and
      high positive predictive value, but low sensitivity.

PMID- 12222612
TI  - Levels of metals in soils of Alcala de Henares, Spain: human health risks.
AB  - The concentrations of aluminium (Al), arsenic (As), beryllium (Be), cadmium (Cd),
      chromium (Cr), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), tin (Sn),
      thallium (Tl), vanadium (V), and zinc (Zn) were determined in soil samples
      collected in Alcala de Henares (Madrid, Spain). Human health risks derived from
      metal inhalation and ingestion of soils were also assessed. For noncarcinogenic
      risks, the current levels of metals were usually lower than those considered as
      safe for the general population. With respect to the potentially carcinogenic
      elements As, Be, Cd, and Cr, the concentrations of Be, Cd, and Cr were lower than
      the reference values, while the average As concentration (3.4 microg/g) was
      higher than the safety limit for risk cancer. In general terms, the potential
      human health impact of ingestion/inhalation through soils of the analyzed
      elements seems to be rather small.

PMID- 12222613
TI  - Variation of nutrient and metal concentrations in aquatic macrophytes along the
      Rio Cachoeira in Bahia (Brazil).
AB  - The use of cuprous fungicides in cocoa production in the southern part of the
      state of Bahia (Brazil) for decades has caused an accumulation of copper in
      various components of the cocoa plantations, and a contamination of regional
      freshwater ecosystems is suspected. Urban and industrial sources are supposed to
      contribute to water pollution and eutrophication of the Rio Cachoeira, the main
      river in this region. In order to study the metal contamination and nutritional
      status of this freshwater ecosystem, samples of the aquatic macrophytes
      Eichhornia crassipes and Pistia stratiotes were collected at seven sites along
      the river course. The samples were analysed for their copper, aluminium,
      chromium, nitrogen and phosphorus concentrations. The levels of heavy metals
      increased in the downstream direction, particularly in the roots of water
      hyacinth. A dramatic increase of nitrogen and phosphorus concentrations in water
      as well as in plant tissues was found in samples collected downstream from the
      city of Itabuna. Metal input and eutrophication were attributed to agricultural,
      industrial and urban sources in the region. Biomonitoring of the water quality
      using aquatic macrophytes as accumulative indicator plants is recommended in
      addition to chemical water analyses.

PMID- 12222614
TI  - Sediment-dissolved organic matter equilibrium partitioning of pentachlorophenol:
      the role of humic matter.
AB  - The dissolved humic matter (HM) has an essential influence on the release of the
      bound pentachlorophenol (PCP) from the solid sediment. It was studied how the
      increase of the dissolved HM concentration affects the equilibrium partitioning
      of PCP between the solid sediment matter and dissolved HM. The lake sedimentary
      and dissolved HM were isolated and their structural compositions were compared
      with elemental analyses, solid-sate 13C NMR spectroscopy and degradative analyses
      by pyrolysis-GC/MS. At the beginning of the equilibrium experiment, the PCP
      contaminant (200 microg l(-1)) was added into the water-sediment slurry system
      having an initial dissolved HM concentration. After 35 days, the system has
      reached an equilibrium and 75.5% of PCP was bound to the total solid sediment,
      1.5% to dissolved HM and 23.0% remained free in water. The dissolved HM content
      was increased by 150% and, at the second equilibrium state after 91 days, only
      63.8% of PCP was bound to the total sediment, and even 6.5% to the dissolved HM
      and 29.7% was free. The structural analyses indicated that the contents of
      aliphatics, aromatics and carboxylic carbons are lower in sediment than in
      dissolved HM, the content of carbohydrates in turn is higher in sediment than in
      dissolved HM, as well as that of different protein descriptors. The closely
      related partition coefficients for the sediment and dissolved HM, however,
      implied that the structural dissimilarity of these sorbents does not play so
      strong roles in the binding affinity of PCP as it would be postulated. The
      relatively great sorption coefficient of the minor colloid-like particle fraction
      in water implied its special but quantitatively quite immaterial roles in the
      partitioning cycle of PCP.

PMID- 12222615
TI  - Remobilisation of 109Cd, 65Zn and 54Mn from freshwater-labelled river sediments
      when mixed with seawater.
AB  - A major fraction of trace metals transported by rivers is associated with
      sediments, especially during flooding, when erosion and resuspension increase
      sediment loads. Upon contact with seawater in estuaries, changes in ionic
      strength and pH may remobilise trace metals from sediment surfaces into more
      bioavailable forms. The objective of the present work was to investigate time
      dependent interactions between trace metals and freshwater sediments and their
      potential remobilisation upon contact with seawater. Two river sediments (one
      organic and one inorganic) were labelled with 109Cd2+, 65Zn2+ and 54Mn2+
      radioactive tracers for periods up to 6 months. Sorption of tracers occurred
      rapidly (> or = 80% sorption, < 1 h), followed by a slower approach to
      pseudoequilibrium. Kd(6 months) were estimated as 460, 480 and 2200 ml/g
      (inorganic sediment) compared to 5300, 4000 and 1200 ml/g (organic sediment) for
      109Cd, 65Zn and 54Mn, respectively. Remobilisation of tracers from labelled
      sediments was studied using sequential extractions. Artificial seawater extracts
      simulated an estuarine environment. Subsequent extractions provided information
      about more strongly sorbed tracer fractions within sediments. Remobilisation of
      109Cd by seawater was significant (> 65%) and least affected by sediment type or
      freshwater labelling time. Redistribution of Cd to strongly bound phases was
      minimal (4% and 1% of 109Cd in strongly oxidisable fractions). Seawater
      remobilisation of 65Zn was significantly greater from the organic sediment (54%)
      compared to the inorganic sediment (8%), where a large fraction of 65Zn (14%)
      became irreversibly bound. Similarly, more 54Mn was remobilised by seawater from
      the organic sediment than the inorganic sediment (66% and 3% remobilised,
      respectively), i.e., 54Mn became more strongly bound in the inorganic sediment. A
      simple three-box model, based on first-order differential equations, was used to
      describe the interaction between tracers in spiked freshwater and two
      operationally defined sediment fractions ("seawater exchangeable" and "seawater
      unexchangeable") up to 6 months of freshwater labelling. Model simulations were
      fitted to experiment data and apparent rate constants were calculated using
      numerical optimisation methods. Sorption ratios from modelling data (i.e., k1/k2)
      were greater for organic compared to inorganic sediments, while fixation ratios
      were higher in inorganic sediments. In conclusion, trace metals can be
      remobilised from sediments on contact with seawater in estuaries. High organic
      content in sediments increased initial sorption of tracers but inhibited
      redistribution to more strongly bound fractions over time, resulting in greater
      remobilisation of tracers when in contact with seawater.

PMID- 12222616
TI  - Exhaled NH3 and excreted Nh4+ in children in unpolluted or urban environments.
AB  - Exhaled ammonia (NH3ex) was measured by chemiluminescence in a group of healthy
      children (n = 20) and in two groups of asthmatic children, one (Group 1) residing
      in a National Park in the mountains (n = 68) and other (Group 2) in an urban area
      (n = 52). We also determined urinary ammonia, nitrates, urea, sodium and
      potassium normalized to osmolarity. Unlike exhaled nitric oxide (NOex), NH3ex was
      not specific to asthma as the children in Group 2 and the controls exhaled more
      ammonia that did the children in Group 1 (14.3 +/- 10.2 and 14.8 +/- 10.3 vs. 5.6
      +/- 4.7 ppb; P < .001, respectively). In the urban environment, all children,
      including the healthy controls, excreted more ammonia (P < .001) and potassium (P
      < .001) but less urea (P < .02) than did the children residing in the National
      Park. These manifestations of moderate metabolic acidosis would favor excretion
      of ammonia at the expense of urea. In the children residing in the National Park,
      positive correlations were observed between NH3ex and urinary ammonia, and
      nitrates, age and morphological parameters. The relationship with the
      morphological parameters is a reflection of the normal physiological formation of
      NH3ex. In the children residing in the urban area, the other endogenous source of
      NH3ex was attributed to a slight disturbance in acid-base balance. In conclusion,
      the measurement of NH3ex appeared of limited interest, although the higher
      urinary urea/NH4+ ratio in Group 1 (P < .0001), especially in the treated
      children, appeared to be linked to the lack of atmospheric pollutants in the
      National Park. Further experimentation is in progress to confirm these findings.

PMID- 12222617
TI  - An input-output balance study for PCBs in humans.
AB  - Polychlorinated biphenyl (PCB) input-output balance studies were performed on
      five male volunteers, aged between 24 and 30, for periods of 8-14 days in 1998.
      Dietary exposure was quantified by the duplicate meals method and varied between
      220 and 460 ng of sigmaPCB (sum of 20 congeners) per day for each of the five
      individuals over the study period. Dietary intake was dominated by congeners 118,
      138, 153 and 180. Average faecal outputs for the five volunteers were 50-290 ng
      of sigmaPCB (sum of 20 congeners) per day for each of the five individuals over
      the same period and was dominated by the same four congeners. Whilst the total
      PCB fluxes were therefore into the body (i.e., accumulation), important
      differences were noted for different individual congeners. PCBs 44, 47, 49, 52,
      60, 66, 101, 105, 110, 118, 149, 151 and 183 all showed net absorption for all
      five volunteers. Some congeners showed a net absorption in some of the
      individuals but net excretion in others, as seen by other workers. These
      congeners (PCBs 138, 153, 180, 187 and 194) are all higher chlorinated congeners
      and lack meta-para-vicinal hydrogen atoms. There were differences in the net
      absorption/excretion between individuals, which appeared to be a function of body
      fat index (BFI). The volunteers with the lowest BFIs showed net excretion for the
      greatest number of congeners, whilst the individual with the highest BFI was a
      net absorber of all the congeners studied. The problems in determining and
      interpreting absorption efficiency values for use in quantitative exposure
      assessments are discussed. Various factors that influence net absorption of PCBs
      and other persistent organic pollutants are identified. These include compound
      properties (including susceptibility to metabolism), the individual's fat status
      and balance, exposure history and diet.

PMID- 12222618
TI  - Environmental fate of alkylphenols and alkylphenol ethoxylates--a review.
AB  - Alkylphenol ethoxylates (APEs) are widely used surfactants in domestic and
      industrial products, which are commonly found in wastewater discharges and in
      sewage treatment plant (STP) effluents. Degradation of APEs in wastewater
      treatment plants or in the environment generates more persistent shorter-chain
      APEs and alkylphenols (APs) such as nonylphenol (NP), octylphenol (OP) and AP
      mono- to triethoxylates (NPE1, NPE2 and NPE3). There is concern that APE
      metabolites (NP, OP, NPE1-3) can mimic natural hormones and that the levels
      present in the environment may be sufficient to disrupt endocrine function in
      wildlife and humans. The physicochemical properties of the APE metabolites (NP,
      NPE1-4, OP, OPE1-4), in particular the high K(ow) values, indicate that they will
      partition effectively into sediments following discharge from STPs. The aqueous
      solubility data for the APE metabolites indicate that the concentration in water
      combined with the high partition coefficients will provide a significant
      reservoir (load) in various environmental compartments. Data from studies
      conducted in many regions across the world have shown significant levels in
      samples of every environmental compartment examined. In the US, levels of NP in
      air ranged from 0.01 to 81 ng/m3, with seasonal trends observed. Concentrations
      of APE metabolites in treated wastewater effluents in the US ranged from < 0.1 to
      369 microg/l, in Spain they were between 6 and 343 microg/l and concentrations up
      to 330 microg/l were found in the UK. Levels in sediments reflected the high
      partition coefficients with concentrations reported ranging from < 0.1 to 13,700
      microg/kg for sediments in the US. Fish in the UK were found to contain up to 0.8
      microg/kg NP in muscle tissue. APEs degraded faster in the water column than in
      sediment. Aerobic conditions facilitate easier further biotransformation of APE
      metabolites than anaerobic conditions.

PMID- 12222620
TI  - The relevance of Rawls' principle of justice for research on cognitively impaired
      patients.
AB  - An ethical conflict arises when we must perform research in the interest of
      future patients, but that this may occasionally injure the interests of today's
      patients. In the case of cognitively impaired persons, the question arises
      whether it is compatible with humane healthcare not only to treat, but also to
      use these patients for research purposes. Some bioethicists and theologians have
      formulated a general duty of solidarity, also pertaining to cognitively impaired
      persons, as a justification for research on these persons. If one examines this
      thesis from the theory of justice according to John Rawls, it is revealed that
      such a duty of solidarity cannot necessarily be extrapolated from Rawls'
      conception of justice. This is at least true of Rawls' difference principle,
      because according to the difference principle only those measures are justifiable
      which serve the interest of the respective least well off. Those measures which
      would engender additional injury for the least well off could not be balanced by
      any utility according to Rawls. However, John Rawls' difference principle is
      subordinate to the first principle, which is that each person has an equal right
      to the most extensive basic liberty compatible with the same liberty for others.
      These "primary goods" are determined by the freedom and integrity of the person.
      This integrity of decisionally impaired persons would be in danger if one would
      abstain from research and thus forego the increase in knowledge related to their
      disease. Thus one could conclude, at least from Rawls' first principle, that
      society must take on a duty to guarantee the degrees of freedom for cognitively
      impaired persons and thus also support the efforts for their healing.

PMID- 12222619
TI  - The professional status of bioethics consultation.
AB  - Is bioethics consultation a profession? With few exceptions, the arguments and
      counterarguments about whether healthcare ethics consultation is a profession
      have ignored the historical and cultural development of professions in the United
      States, the ways social changes have altered the work and boundaries of all
      professions, and the professionalization theories that explain how modern
      societies institutionalize expertise in professions. This interdisciplinary
      analysis begins to fill this gap by framing the debate within a larger
      theoretical context heretofore missing from the bioethics literature.
      Specifically, the question of whether ethics consultation is a profession is
      examined from the perspectives of trait theory, Wilensky's five-stage process of
      professionalization, Abbott's interdependent system of professions, and Haug's
      deprofessionalization thesis. While healthcare ethics consultation does not meet
      the criteria to claim professional status, neither could most professions pass
      these ideal theoretical standards. Instead of a yes or no dichotomous response to
      the question, it is more helpful to envision a professionalization continuum with
      sales clerks or carpenters at one end and medicine or law at the other. During
      the past decade healthcare ethics consultation has been moving along this
      continuum toward greater professional status.

PMID- 12222621
TI  - Medical decision-making: an argument for narrative and metaphor.
AB  - This study examines the processes of decision-making used by intensive care
      (critical care) specialists. Ninety-nine specialists completed a questionnaire
      involving three clinical cases, using a novel methodology investigating the role
      of uncertainty and temporal-related factors, and exploring a range of ethical
      issues. Validation and triangulation of the results was done via a comparison
      study with a medically lay, but highly informed group of 37 law students. For
      both study groups, constructing reasons for a decision was largely an
      interpretative and imaginative exercise that went beyond the data (as presented),
      commonly resulting in different reasons supporting the same conclusions and
      similar reasons supporting opposite conclusions. The skills of ethical
      imagination and interpretation were related to an individual's prior lived
      experience, construed in the broadest sense. Application of these skills of
      ethical imagination and interpretation always occurred, to some degree, in a
      state of uncertainty and almost always involved temporal relationships. Using
      these results, a theory of ethical decision-making is proffered. Three levels or
      types of reasoning processes may be present. Type I decision-making involves the
      application of rules, usually in a deductive fashion. Type II decision-making is
      characterised by a process where a plurality of reasons are balanced, weighed and
      sifted with each other. Type III decision-making is intimately linked with
      respondents lived experiences and 'crafts' the content of type I and II reasoning
      processes, via the application of ethical imagination and interpretation.
      Relationships between these three types of reasoning processes, and with
      narrative ethics, are also discussed.

PMID- 12222622
TI  - Human dignity and the ethics and aesthetics of pain and suffering.
AB  - Inasmuch as unmitigated pain and suffering are often thought to rob human beings
      of their dignity, physicians and other care providers incur a special duty to
      relieve pain and suffering when they encounter it. When pain and suffering cannot
      be controlled it is sometimes thought that human dignity is compromised. Death,
      it is sometimes argued, would be preferred to a life without dignity. Reasoning
      such as this trades on certain preconceptions of the nature of pain and
      suffering, and of their relationships to dignity. The purpose of this paper is to
      lay bare these preconceptions. The duties to relieve pain and suffering are
      clearly matters of moral obligation, as is the duty to respond appropriately to
      the dignity of other persons. However, it is argued that our understanding of the
      phenomena of pain and suffering and their relationships to human dignity will be
      expanded when we explore the aesthetic dimensions of these various concepts. On
      the view presented here the life worth living is both morally good and
      aesthetically beautiful. Appropriate "suffering with" another can help to
      maintain and restore the dignity of the relationships involved, even as it
      preserves and enhances the dignity of patient and caregiver alike.

PMID- 12222623
TI  - The distributive justice principle.

PMID- 12222624
TI  - Impact of the atherosclerotic process in patients with diabetes.
AB  - Between 120 and 140 million people suffer from diabetes mellitus (type 1 and type
      2) worldwide, and this number may well double by the year 2025. Patients with
      diabetes are at increased risk of atherosclerosis and its clinical sequelae:
      coronary, peripheral vascular, and cerebrovascular diseases. Concurrently, the
      most common cause of death in persons with diabetes is myocardial infarction. The
      pathogenesis, progression, and epidemiology of atherosclerotic disease are
      distinct in patients with diabetes. Atherosclerosis can develop much earlier in
      life, and at an accelerated rate, compared with non-diabetic individuals. One of
      the factors responsible for increased atherosclerosis is related to the
      atherogenic lipid profile in diabetes. The pathobiological processes that are
      responsible for transforming dormant atherosclerotic plaques into active rupture
      prone plaques may be enhanced in diabetes as well. It follows that a major
      challenge in the treatment of patients with diabetes is to reduce the risk of
      atherosclerotic disease. The third National Cholesterol Education Program (NCEP)
      report recently recommended that the management of dyslipidaemia in patients with
      diabetes should be as aggressive as in those with established coronary heart
      disease (CHD). The NCEP Adult Treatment Panel III guidelines recommend statins
      for patients at elevated risk for CHD.

PMID- 12222625
TI  - Controlling lipid levels in diabetes.
AB  - Coronary heart disease (CHD) is associated with a 2- to 4-times greater risk of
      morbidity and mortality in patients with type 2 diabetes than in non-diabetic
      individuals. Dyslipidaemia is an important CHD risk factor in diabetic patients.
      The key atherogenic features of diabetic dyslipidaemia are elevated levels of
      serum triglycerides, low levels of high density lipoprotein (HDL) cholesterol,
      and the preponderance of small, dense low density lipoprotein (LDL). As a result,
      treatment guidelines for diabetic dyslipidaemia recommend elevated LDL
      cholesterol and triglyceride levels and low HDL cholesterol levels as targets of
      therapy. Unfortunately, however, these lipid abnormalities often persist despite
      best efforts to control hyperglycaemia, improve diet, and increase physical
      exercise, and therefore demand specific therapeutic intervention. Statins are the
      first choice for LDL cholesterol lowering as they are effective and well
      tolerated, and do not have adverse effects on glycaemic control. Furthermore,
      recent evidence suggests that statins may also be employed to treat moderately
      elevated levels of triglycerides. An increasing number of primary and secondary
      prevention trials have shown that lipid-lowering therapy with statins can
      significantly reduce the risk of CHD events in patients with diabetic
      dyslipidaemia.

PMID- 12222626
TI  - Controlling hypertension in diabetes.
AB  - Patients with type 2 diabetes are especially vulnerable to both large and small
      vessel injury from elevated arterial blood pressure. The frequent combination of
      hypertension and diabetes is, therefore, associated with a high risk of
      cardiovascular events and end-stage renal disease. The beneficial therapeutic
      effects of angiotensin-converting enzyme (ACE) inhibitors, calcium channel
      blockers (CCBs), and other antihypertensive drugs in patients with type 2
      diabetes have been well established in placebo-controlled trials, and there
      appears to be no evidence of differences between treatment regimens based on
      different drug classes. In addition, a number of major clinical trials have
      supported a policy of aggressive blood pressure lowering in patients with type 2
      diabetes. In the UK Prospective Diabetes Study, for example, tight control of
      blood pressure was demonstrated to produce clinically important reductions in the
      risk of complications related to type 2 diabetes compared with less tight
      control. In most hypertensive patients, however, a reduction to a recommended
      level <130/85 mm Hg is unlikely to be achieved by monotherapy. Consequently, the
      combination of ACE inhibitors with other first-line drugs, such as CCBs,
      diuretics and beta-blockers, is recommended for the therapeutic management of
      hypertensive diabetic patients.

PMID- 12222627
TI  - Evolving therapeutic strategies for retarding progression of diabetic nephropathy
      -an update for 2002.
AB  - During the past few years, several major intervention trials have been conducted
      in an attempt to determine the efficacy of specific antihypertensive agents in
      retarding progression of diabetic nephropathy. These studies have clearly
      demonstrated the importance of renin-angiotensin system blockade in attenuating
      progressive renal disease. The preferred initial therapy is an angiotensin
      converting enzyme (ACE) inhibitor, or an angiotensin type I (AT1) receptor
      antagonist based on the recent 'landmark' proof-of-concept trials--the Irbesartan
      Type 2 Diabetic Nephropathy Trial (IDNT) and the Reduction of Endpoints in NIDDM
      with Angiotensin II Antagonist Losartan (RENAAL). However, these clinical trials
      also demonstrate that aggressive blood pressure targets are needed in patients
      with diabetes and hypertension. This frequently requires multiple-drug therapy
      with several different classes of antihypertensive agents. Data from several
      clinical trials, including RENAAL, suggest that calcium antagonists may be added
      to ACE inhibitor or AT1 receptor antagonist therapy as needed to achieve target
      blood pressure. Calcium antagonists could, therefore, constitute an important
      component of the antihypertensive regimen in the management of patients with
      diabetic nephropathy.

PMID- 12222628
TI  - Answering the unanswered questions: ongoing trials of statins and
      antihypertensives in type 2 diabetes.
AB  - Dyslipidaemia and hypertension contribute to an excess risk of coronary heart
      disease (CHD) in patients with type 2 diabetes. A number of landmark primary and
      secondary prevention trials have demonstrated that lipid-lowering therapy with
      HMG-CoA reductase inhibitors (statins), and antihypertensive therapy with
      angiotensin-converting enzyme inhibitors and calcium channel blockers (CCBs),
      reduce CHD risk in the non-diabetic population. However, many questions remain
      unanswered about the use of these therapies in patients with type 2 diabetes. To
      address the most important of these questions, several major trials are under way
      that will provide more data on the benefits of lipid-lowering and
      antihypertensive therapy in type 2 diabetes. These include studies of
      atorvastatin, an established member of the statin class, with over 22 million
      patient-years' experience and an excellent safety profile. Similarly, the
      Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial
      (ALLHAT) and the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) will determine
      the efficacy of the CCB, amlodipine, in patients with concomitant type 2 diabetes
      and hypertension.

PMID- 12222629
TI  - Commercial bacterial starter cultures for fermented foods of the future.
AB  - Starter cultures for fermented foods are today developed mainly by design rather
      than by screening. The design principles are based on knowledge of bacterial
      metabolism and physiology as well as on the interaction with the food product. In
      the genomics era, we will obtain a wealth of data making design on a rational
      basis even simpler. The design tools available are food grade tools for genetic,
      metabolic and protein engineering and an increased use of laboratory automation
      and high throughput screening methods. The large body of new data will influence
      the future patterns of regulation. It is currently difficult to predict in what
      direction the future regulatory requirements will influence innovation in the
      food industry. It can either become a promoting force for the practical use of
      biotechnology to make better and safer products, or it can be limiting the use of
      starter cultures to a few strains with official approval. Successful cultures
      based on modern technology is expected to be launched in the areas of:
      probiotics, bioprotection, general improvement of yield and performance for the
      existing culture market and probably the introduction of cultures for fermenting
      other food products. A scientific basis for dramatic innovations that could
      transform the culture industry is currently being established.

PMID- 12222630
TI  - Predictive microbiology: providing a knowledge-based framework for change
      management.
AB  - This contribution considers predictive microbiology in the context of the Food
      Micro 2002 theme, "Microbial adaptation to changing environments". To provide a
      reference point, the state of food microbiology knowledge in the mid-1970s is
      selected and from that time, the impact of social and demographic changes on
      microbial food safety is traced. A short chronology of the history of predictive
      microbiology provides context to discuss its relation to and interactions with
      hazard analysis critical control point (HACCP) and risk assessment. The need to
      take account of the implications of microbial adaptability and variable
      population responses is couched in terms of the dichotomy between classical
      versus quantal microbiology introduced by Bridson and Gould [Lett. Appl.
      Microbiol. 30 (2000) 95]. The role of population response patterns and models as
      guides to underlying physiological processes draws attention to the value of
      predictive models in development of novel methods of food preservation. It also
      draws attention to the paradox facing today's food industry that is required to
      balance the "clean, green" aspirations of consumers with the risk, to safety or
      shelf life, of removing traditional barriers to microbial development. This part
      of the discussion is dominated by consideration of models and responses that lead
      to stasis and inactivation of microbial populations. This highlights the
      consequence of change on predictive modelling where the need is now to develop
      interface and non-thermal death models to deal with pathogens that have low
      infective doses for general and/or susceptible populations in the context of
      minimal preservation treatments. The challenge is to demonstrate the validity of
      such models and to develop applications of benefit to the food industry and
      consumers as was achieved with growth models to predict shelf life and the
      hygienic equivalence of food processing operations.

PMID- 12222631
TI  - Quantitative microbial risk assessment exemplified by Staphylococcus aureus in
      unripened cheese made from raw milk.
AB  - This paper discusses some of the developments and problems in the field of
      quantitative microbial risk assessment, especially exposure assessment and
      probabilistic risk assessment models. To illustrate some of the topics, an
      initial risk assessment was presented, in which predictive microbiology and
      survey data were combined with probabilistic modelling to simulate the level of
      Staphylococcus aureus in unripened cheese made from raw milk at the time of
      consumption. Due to limited data and absence of dose-response models, a complete
      risk assessment was not possible. Instead, the final level of bacteria was used
      as a proxy for the potential enterotoxin level, and thus the potential for
      causing illness. The assessment endpoint selected for evaluation was the
      probability that a cheese contained at least 6 log cfu S. aureus g(-1) at the
      time of consumption; the probability of an unsatisfactory cheese, P(uc). The
      initial level of S. aureus, followed by storage temperature had the largest
      influence on P(uc) at the two pH-values investigated. P(uc) decreased with
      decreasing pH and was up to a factor of 30 lower in low pH cheeses due to a
      slower growth rate. Of the model assumptions examined, i.e. the proportion of
      enterotoxigenic strains, the level of S. aureus in non-detect cheeses, the
      temperature limit for toxin production, and the magnitude and variability of the
      threshold for an unsatisfactory cheese, it was the latter that had the greatest
      impact on P(uc). The uncertainty introduced by this assumption was in most cases
      less than a factor of 36, the same order of magnitude as the maximum variability
      due to pH. Several data gaps were identified and suggestions were made to improve
      the initial risk assessment, which is valid only to the extent that the limited
      data reflected the true conditions and that the assumptions made were valid.
      Despite the limitations, a quantitative approach was useful to gain insights and
      to evaluate several factors that influence the potential risk and to make some
      inferences with relevance to risk management. For instance, the possible effect
      of using starter cultures in the cheese making process to improve the safety of
      these products.

PMID- 12222632
TI  - Development and application of new nucleic acid-based technologies for microbial
      community analyses in foods.
AB  - Several challenges still persist in the analysis of microorganisms in foods,
      particularly in studies of complex communities. Nucleic acid-based methods are
      promising tools in addressing new questions concerning microbial communities. We
      have developed several new methods in the field of nucleic acid-based microbial
      community analyses. These methods cover both sample preparation and detection
      approaches. The sample preparation method involves simplified DNA purification
      using paramagnetic beads. As an extension of this method, the same paramagnetic
      beads are used for both cell separation and DNA purification. This enables full
      automation. The separate detection of viable and dead bacteria is a major issue
      in nucleic acid-based diagnostics. We have applied a living/dead dye that binds
      covalently to DNA and inhibits the PCR from dead cells. In addition, a DNA array
      based detection assay has been developed. The assay combines the specificity
      obtained by enzymatic labeling of DNA probes with the possibility of detecting
      several targets simultaneously by DNA array hybridization. In combination with
      16S rDNA amplification, this is a promising tool for community analyses. Also, we
      have developed a novel approach for multiplex quantitative PCR. The multiplex PCR
      has been combined with our DNA array-based detection method. Finally, we are now
      in the process of adapting a system for monitoring microbial growth and death in
      real-time through the tagging of bacteria with green fluorescent protein (GFP)
      combined with fluorescence detection using a high-resolution confocal laser
      scanner.

PMID- 12222633
TI  - Prions, BSE and food.
AB  - Biochemical and biophysical properties of prions including possible inactivation
      methods are reviewed. Possible molecular markers of transmissible spongiform
      encephalopathy (TSE) and mechanisms behind infectivity and correlation with
      clinical symptoms are discussed. The risk of Bovine Spongiform Encephalopathy
      (BSE) for humans i.e. variant Creutzfeldt-Jakob Disease (cCJD) is addressed in
      detail. The consequences of the emergence of the new cCJD and the lack of
      information on the infectivity of cCJD at the clinical stage of the disease in
      relation to the need to reconsider the biological concepts currently used in
      microbiology.

PMID- 12222634
TI  - Stress and the single cell: intrapopulation diversity is a mechanism to ensure
      survival upon exposure to stress.
AB  - We traditionally celebrate the capacity of bacteria for growth in a diverse range
      of environmental niches. As the attention has switched to their survival, we are
      no less impressed by the diversity of mechanisms that aid survival upon exposure
      to a variety of stresses. Mechanistically, we usually measure adaptation by the
      changes that occur upon rapid transfer from condition A to B. Implicit in such
      analyses is the homogeneity of the population of cells in terms of their
      biochemistry and responsiveness. In contrast, the literature contains many
      reports of heterogeneity within bacterial populations. A practical importance of
      such heterogeneity is the ability of a small fraction of any population to
      survive exposure to stresses that kill the majority of the population. The
      origins and properties of such organisms have been receiving renewed attention.
      This brief review considers some of the routes by which heterogeneity is
      generated in bacterial populations and suggests that such inherent transient
      diversity in phenotype of individual cells is a survival aid.

PMID- 12222635
TI  - New directions in foodborne disease prevention.
AB  - Food safety is an important part of public health linking health to agriculture
      and other food production sectors. For over a century, developments in food
      production and new control philosophies have contributed to food safety systems
      in most developed countries perceived by many to be efficient in the prevention
      of foodborne disease. Nevertheless, a number of problems still remain dominant,
      one of these being the high level of foodborne microbiological diseases which
      seem, for some pathogens, to have increased over the last decades. Although there
      is an urgent need for better foodborne disease data in most countries, the paper
      attempts an analysis of the background to these problems using available data to
      illustrate the developments for some of the major foodborne pathogens. Some of
      the shortcomings of present food safety systems are discussed, as are new
      principles to improve food safety strategies. A new paradigm for the integration
      of research data, food-control monitoring, epidemiological investigations and
      disease surveillance in a renewed effort to manage and lower foodborne risk is
      presented. Within this paradigm, the development of an interdisciplinary approach
      with direct interaction between surveillance and risk analysis systems is
      described as a potential basis for improved foodborne disease prevention.
      Specific consideration is given to the situation in developing countries,
      suggesting a leap forward past the experience of noncollaboration between the
      disciplines in many developed countries. Today, food safety is one of WHO's top
      11 priorities and the Organisation calls for more systematic and aggressive steps
      to be taken to significantly reduce the risk of microbiological foodborne
      diseases. Dealing with this challenge is one of the major challenges for the 21st
      century in regard to food safety, implying a significant redirection of food
      microbiology efforts in many parts of the world.

PMID- 12222636
TI  - Emerging foodborne pathogens.
AB  - The broad spectrum of foodborne infections has changed dramatically over time, as
      well-established pathogens have been controlled or eliminated, and new ones have
      emerged. The burden of foodborne disease remains substantial: one in four
      Americans is estimated to have a significant foodborne illness each year. The
      majority of these illnesses are not accounted for by known pathogens, so more
      must remain to be discovered. Among the known foodborne pathogens, those more
      recently identified predominate, suggesting that as more and more is learned
      about pathogens, they come under control. In addition to the emergence or
      recognition of new pathogens, other trends include global pandemics of some
      foodborne pathogens, the emergence of antimicrobial resistance, the
      identification of pathogens that are highly opportunistic, affecting only the
      most high-risk subpopulations, and the increasing identification of large and
      dispersed outbreaks. New pathogens can emerge because of changing ecology or
      changing technology that connects a potential pathogen with the food chain. They
      also can emerge de novo by transfer of mobile virulence factors, often through
      bacteriophage. Though this is rarely observed, it can be reconstructed. Better
      understanding of the ecology and dynamics of phage transmission among bacteria
      will help us to understand the appearance of new pathogens in the future. One may
      look for emerging foodborne pathogens among the silent zoonoses, and among the
      severe infections affecting the immunocompromised humans. We should expect the
      unexpected. In the past, separating human sewage and animal manure from human
      food and water supplies was critical to improving public health. Now, our health
      depends increasingly on the safety of the feed and water supplies for the animals
      themselves. The successes of the 20th century and the new challenges we face mean
      that public health vigilance, careful investigation of new problems, responsible
      attention to food safety from farm to table, and partnerships to bring about new
      foodborne disease control measures will be needed for the foreseeable future.

PMID- 12222637
TI  - Antibiotic resistance in food-related bacteria--a result of interfering with the
      global web of bacterial genetics.
AB  - A series of antibiotic resistance genes have been sequenced and found to be
      identical or nearly identical in various ecological environments. Similarly,
      genetic vectors responsible for assembly and mobility of antibiotic resistance
      genes, such as transposons, integrons and R plasmids of similar or identical type
      are also widespread in various niches of the environment. Many zoonotic bacteria
      carry antibiotic resistance genes directly from different food-producing
      environments to the human being. These circumstances may have a major impact on
      the degree for success in treating infectious diseases in man. Several recent
      examples demonstrate that use of antibiotics in all parts of the food production
      chain contributes to the increasing level of antibiotic resistance among the food
      borne pathogenic bacteria. Modern industrialized food production adds extra
      emphasis on lowering the use of antibiotics in all parts of agriculture,
      husbandry and fish farming because these food products are distributed to very
      large numbers of humans compared to more traditional smaller scale niche
      production.

PMID- 12222638
TI  - Physiological and mathematical aspects in setting criteria for decontamination of
      foods by physical means.
AB  - In heat processing, microbial inactivation is traditionally described as log
      linear. As a general rule, the relation between rate of inactivation and
      temperature is also described as a log-linear relation. The model is also
      sometimes applied in pressure and in pulsed electric field (PEF) processing. The
      model has proven its value by the excellent safety record of the last 80 years,
      but there are many deviations from log-linearity. This could lead to either over
      processing or under-processing resulting in safety problems or, more likely,
      spoilage problems. As there is a need for minimal processing, accurate
      information of the inactivation kinetics is badly needed. To predict inactivation
      more precisely, models have been developed that can cope with deviations of
      linearity. As extremely low probabilities of survival must be predicted,
      extrapolation is almost always necessary. However, extrapolation is hardly
      possible without knowledge of the nature of nonlinearity. Therefore, knowledge of
      the physiology of inactivation is necessary. This paper discusses the physiology
      of denaturation by heat, high pressure and pulse electric field. After discussion
      of the physiological aspects, the various aspects of the development of
      inactivation models will be addressed. Both general and more specific aspects are
      discussed such as choice of test strains, effect of the culture conditions,
      conditions during processing and recovery conditions and mathematical modelling
      of inactivation. In addition to lethal inactivation, attention will be paid to
      sublethal inactivation because of its relevance to food preservation. Finally,
      the principles of quantitative microbiological risk assessment are briefly
      mentioned to show how appropriate inactivation criteria can be set.

PMID- 12222639
TI  - Food spoilage--interactions between food spoilage bacteria.
AB  - Food spoilage is a complex process and excessive amounts of foods are lost due to
      microbial spoilage even with modern day preservation techniques. Despite the
      heterogeneity in raw materials and processing conditions, the microflora that
      develops during storage and in spoiling foods can be predicted based on knowledge
      of the origin of the food, the substrate base and a few central preservation
      parameters such as temperature, atmosphere, a(w) and pH. Based on such knowledge,
      more detailed sensory, chemical and microbiological analysis can be carried out
      on the individual products to determine the actual specific spoilage organism.
      Whilst the chemical and physical parameters are the main determining factors for
      selection of spoilage microorganisms, a level of refinement may be found in some
      products in which the interactive behavior of microorganisms may contribute to
      their growth and/or spoilage activity. This review gives three such examples. We
      describe the competitive advantage of Pseudomonas spp. due to the production of
      iron-chelating siderophores, the generation of substrates for spoilage reactions
      by one organism from another microorganism (so-called metabiosis) and the up
      regulation of phenotypes potentially involved in spoilage through cell-to-cell
      communication. In particular, we report for the first time the widespread
      occurrence of N-acyl homoserine lactones (AHL) in stored and spoiling fresh foods
      and we discuss the potential implications for spoilage and food preservation.

PMID- 12222640
TI  - Gut bacteria and health foods--the European perspective.
AB  - Probiotics, prebiotics, and synbiotics aimed at improving intestinal health
      currently represent the largest segment of the functional foods market in Europe,
      Japan and Australia. Evidence continues to emerge demonstrating that these
      ingredients have the potential to improve human health in specific intestinal
      disorders. The European Commission, through its 5th Framework Programme, is
      presently focusing on a substantial effort in the science of the intestinal
      microbiota, its interaction with its host and methods to manipulate its
      composition and activity for the improvement of human health and well being.
      Eight multicentre and multidisciplinary research projects now cover a range of
      topics required for the development of efficacious probiotic foods, from
      understanding probiotic mechanisms at a molecular level; developing technologies
      to ensure delivery of stable products; and demonstrating safety and efficacy of
      specific probiotics in defined treatment targets. This concerted research effort
      promises to provide us with an enhanced understanding of the human intestinal
      microbiota's role in health and disease, and new approaches and products to
      tackle a variety of intestinal problems.

PMID- 12222641
TI  - Craniofacial morphology in obese adolescents.
AB  - Overweight and obesity are growing problems in the world today. A recent survey
      shows that about 30% of the adolescent and adult Swedish population is overweight
      or obese. The etiology is a combination of many factors, the most important of
      which are physical inactivity and high caloric diet. Obese children have a normal
      to accelerated growth rate despite low growth hormone (GH) levels. The aim of our
      study was to investigate whether craniofacial morphology differs between obese
      adolescents and normal weight adolescents. Lateral cephalograms from 39
      adolescents with obesity, aged 14-16 years, were analysed and compared with
      lateral cephalograms from an equal number of sex- and aged-matched controls.
      Compared to the controls, the subjects in the obesity group showed increased
      mandibular length, prognathic jaws and a reduced upper anterior face height.
      Despite low GH levels, obese children have normal levels of insulin-like growth
      factor (IGF-1). Since we found an advanced craniofacial growth in obese
      adolescents with low GH and high IGF-1 serum levels, craniofacial growth may be
      more dependent on free circulating LGF-1 than on the locally produced portion.

PMID- 12222642
TI  - Specific IgA subclass responses in serum and saliva: a 12-month follow-up study
      after parenteral booster immunization with tetanus toxoid.
AB  - Specific IgA subclass antibodies against tetanus toxoid in serum, parotid saliva,
      and whole saliva were quantified after booster immunization. Samples from 14
      healthy individuals were collected before and 1, 6, and 12 months after
      subcutaneous injection with Duplex (0.23 ml tetanus toxoid 30 Lf/mL and
      diphtheria 7.3 Lf/mL). Samples of whole saliva were also collected after 2 weeks.
      Specific IgA1 and IgA2 subclass antibodies to tetanus toxoid were quantified by
      enzyme-linked immunosorbent assay (ELISA). In this quantitative method, chimeric
      IgA1 and IgA2 antibodies directed against NP (4-hydroxy-3-nitrophenacetyl) were
      used as standards. Total levels of IgA1 and IgA2 were measured using a
      nephalometer or ELISA. Immunization with tetanus toxoid resulted in raised mean
      values of specific IgA1 and IgA2 antibodies against tetanus toxoid in serum after
      1 month. Compared with the baseline, the mean value of specific IgA1 antibodies
      showed a 2.6-fold increase (mean value 10.47 microgram/mL) in serum, and that of
      specific IgA2 antibodies a 2.7-fold increase (mean value 0.93 microgram/mL).
      Specific IgA subclass antibody levels in parotid and whole saliva were unchanged
      after 1 month. The ratio of specific IgA subclass antibodies to total IgA
      subclass antibodies was 3 to 10 times higher in parotid saliva compared with
      whole saliva. In conclusion, subcutaneous booster immunization with tetanus
      toxoid induced immune responses of both antigen-specific IgA1 and IgA2 subclass
      antibodies in serum with the same increase, whereas the levels of specific IgA
      subclass antibodies in secretory fluids were unchanged. The ratio of specific IgA
      subclass antibodies to immunoglobulins was higher in parotid saliva compared with
      whole saliva.

PMID- 12222643
TI  - Changes in expansion and mechanical strength during water storage of a
      traditional and three modified resin composites.
AB  - Four types of resin composites (Dyract AP (DYR), Definite (DEF), Ariston pHc
      (ARI), and Spectrum TPH (SPE)) were tested after water storage for up to 180
      days. The test parameters were flexural strength, flexural modulus, and marginal
      gaps at fillings in cylindrical cavities. The cavity tests were performed in two
      ways. One series of filings was finished shortly after curing and the maximal
      gaps were followed with time during water storage. Another series was finished
      immediately before gap size measurement and after water storage for various
      periods. Absence of or reduced gap sizes at 180 days compared to 1 h or 1 day was
      obsenred for all materials and with both methods. At 180 days, DYR and ARI showed
      significantly smaller gap sizes than those observed with DEF and SPE. No
      significant differences in flexural strength were observed when means at 180 days
      were compared to those observed at 1 day. DEF, ARI, and SPE showed a significant
      increase in flexural moduli at 180 days compared to 1 day, while DYR showed none.
      It is concluded that fillings made of Dyract AP or Ariston pHc may show absence
      of or very small gap sizes between filling and cavity wall after 6 months and
      with no significant reduction in mechanical strength.

PMID- 12222644
TI  - Effects of cyclophosphamide on the femoral epiphyseal growth plate in young
      Sprague-Dawley rats.
AB  - The purpose of this study was to assess the effects of cyclophosphamide on
      cartilaginous growth and differentiation. Cyclophosphamide is a drug commonly
      used in the treatment of neoplastic diseases and in preparation for bone marrow
      transplantation. Eighteen Sprague-Dawley rats divided into control and
      experimental groups received 2 i.p. injections of either saline or
      cyclophosphamide (30 mg/kg) with a 3-day interval starting from day 10 after
      birth. Effects on the proximal femoral epiphyses were evaluated
      histomorphometrically as well as semi-quantitatively at day 31 after birth.
      Results showed a significant reduction in length of the cyclophosphamide-treated
      femora compared to the controls. This could be attributed to a significant
      reduction in the thickness of the growth zone. Cell differentiation throughout
      the growth plates was clearly disturbed, involving nesting of cells, loss of
      polarity, and impaired maturation as seen by areas of excessive hyalinization.
      Although the effects of cyclophosphamide on the growth plates were significant
      compared to controls, the changes were not as extensive as previous reports have
      indicated. This could be attributed primarily to the fact that a comparatively
      low dose of the drug was used in the present study. Also, a period of recovery
      was allowed prior to evaluation. Nevertheless, significant effects remained which
      should be considered when treating young children with cyclophosphamide.

PMID- 12222645
TI  - Quality of fixed prosthodontics after twenty-two years.
AB  - After an observation period of 22 years, this study was conducted to clinically
      examine and interview patients who in 1984 and 1989 had participated in similar
      investigations regarding the quality, over time. of treatments with fixed partial
      dentures. The patients were examined by two standardized and experienced
      clinicians using thc California Dental Association quality rating system, their
      results indicating that after 22 years the overall survival rates were 46.5% and
      41.1% for the originally placed crowns and pontics, respectively. However, a
      continuing decrease of the crown quality rating was noted during the more than 20
      year-long observation period. Restorative treatments with common types of fixed
      partial dentures can therefore be regarded as both safe and reliable over long
      periods of time.

PMID- 12222646
TI  - Effect of artificial occlusal interferences depends on previous experience of
      temporomandibular disorders.
AB  - Studies on artificial interferences in subjects with no temporomandibular (TMD)
      history have shown adaptation to the interference within a fairly short period of
      time. The role of occlusal factors in the etiology of TMD has therefore been
      questioned. The results might have been different, however, if subjects with a
      prior TMD history had been included in the study groups. To test this assumption
      in a randomized double-blind clinical set-up, we included healthy women without
      (n = 26) as well as with (n = 21) an earlier TMD history. Both groups were
      randomly divided into true and placebo interference groups. Artificial
      interferences were introduced in the true interference groups and simulated in
      the placebo groups. The subjects were followed for 2 weeks, after which the
      interferences were removed. The subjects without a TMD history showed fairly good
      adaptation to the interferences, but the subjects with a TMD history and true
      interferences showed a significant increase in clinical signs compared to the
      other groups. We suggest that the etiological role of occlusal interferences in
      TMD may not have been correctly addressed in previous studies with artificial
      interferences and allow no conclusions as regards TMD etiology.

PMID- 12222647
TI  - Dental health patterns in young adults in Lithuania: an exploratory, analytical
      approach.
AB  - Patterns of variation in experience related to caries and treatment with regard
      to psychosocial, socio-economic, lifestyle, and oral healthcare-related
      characteristics were explored. A random sample of 382 (response rate 51%)
      subjects residing in 10 areas of Lithuania was examined (35 to 44-year-olds).
      Participants were given a dental examination and asked to complete a structured
      questionnaire. Experience related to caries and treatment differed with regard to
      residency and between genders. Analysis of self-reported data elucidated
      different aspects of psychosocial and socio-economic status and a variety of
      lifestyle factors. Interrelationships between the studied determinants were also
      analysed. Different patterns of dental health were revealed for men and women and
      for urban and rural participants. It can be concluded that factors influencing
      the dental status of Lithuanians are not only multiple, they seem also to
      influence dental health in complex ways. An exploratory approach should therefore
      be considered as a prerequisite to a causal approach of studying caries in
      populations.

PMID- 12222648
TI  - Temperament and acceptance of dental treatment under sedation in preschool
      children.
AB  - The major aim of the study was to investigate whether differences concerning
      acceptance of dental treatment and amnesia after rectal sedation with midazolam
      can be explained by temperament traits in the child. Fifty children (1.5 4.0
      years), consecutively referred for dental extractions because of dental trauma or
      caries, were sedated with midazolam 0.3 mg kg(-1) rectally. Level of sedation
      (state of mind) was assessed according to Wilton before and 10 min after
      administration of the sedative. The children's acceptance of procedures during
      the oral examination, the administration of the sedative, and the dental
      treatment were assessed according to Holst. Acceptance of an injection of local
      anesthesia and tooth extraction was dichotomized as satisfactory (n = 26) or
      unsatisfactory (n = 24). The parent assessed temperament using the Emotionality
      Activity Sociability (EAS) Scale of Child Temperament. Amnesia was evaluated by
      the parent on the following day. The relation between temperament and outcome
      variables was analyzed using a multiple logistic regression analysis. Children
      regarded as shy by the parent were at significantly greater risk of
      unsatisfactory acceptance of the dental treatment (P< 0.05). High scores of
      negative emotionality were significantly related to less amnesia (P < 0.05). We
      conclude that parental ratings of their child's temperament are valuable in
      predicting a child's acceptance of dental treatment under sedation.

PMID- 12222649
TI  - Salivary variables in relation to tobacco smoking and female sex steroid hormone
      use in 30 to 59-year-old women.
AB  - Several systemic conditions may have an influence on oral health. Hormone
      replacement therapy (HRT) has a positive effect on alveolar bone of menopausal
      women and smoking a negative effect. However, little is known about their effect
      on saliva. The purpose of this study was to examine the effect of hormone-use and
      tobacco smoking on the composition of saliva, in particular on the inorganic
      constituents. Salivary samples were collected from a representative study group
      comprising 1,013 women (30-59 years) participating in a pre-screen referral
      program for osteoporosis. The participants were divided into 2 subgroups
      according to age. The younger group (< or = 45 years) comprised 413 women and the
      older group (> or = 50 years) 600 women. Salivary calcium, magnesium, sodium,
      potassium, inorganic phosphate, total protein, and flow rate of paraffin
      stimulated saliva were measured. In the older age group, female sex steroid users
      (hormone users) had lower salivary protein concentrations than non-users. Smoking
      was associated with high salivary calcium, magnesium, and potassium levels in the
      group of older participants. Neither tobacco smoking nor female sex steroid
      hormones had any significant effect on the salivary composition in the younger
      age group. In conclusion, smoking was reflected more clearly than female sex
      steroid hormone-use in the inorganic composition of saliva in the older age
      group. The salivary composition was not affected by hormone-use or by smoking
      among the younger age group.

PMID- 12222650
TI  - Influence of cementum on the demineralization and remineralization processes of
      root surface caries in vitro.
AB  - The influence of the nature of the root surface on the demineralization and
      remineralization processes within artificial fluoride-treated caries lesions was
      investigated using microscopic and X-ray microanalytical methods. Traces of
      fluoride were detected in the outer parts (about 25 micrometers) of the lesions
      after the application of fluorides, and a high mineral content was proved for the
      same region by means of microanalytical calcium estimation. The location of this
      mineral-rich band in relation to the root surface was deeper into the root
      depending on the existence and thickness of a cementum layer. However, within the
      dentine the location and intensity of the mineral content were unaffected by the
      cementum. Investigation of artificial caries lesions without fluoride treatment
      showed the following: The degree of mineralization was kept at a higher level
      near the root surface in the presence of cementum. Consequently, a cementum layer
      gives some initial caries resistance of the root surface.

PMID- 12222651
TI  - Efficiency of occlusal appliance therapy in secondary otalgia and
      temporomandibular disorders.
AB  - In clinical practice, it is commonly assumed that occlusal splints have
      therapeutic value in the treatment of temporomandibular disorders CTMD), but the
      evidence based on randomized controlled trials is scarce. This study evaluated
      the short-term (10-week) efficacy of a stabilization splint in subjects with
      recurrent secondary otalgia and active TMD treatment need using a randomized,
      controlled, double-blind design. Thirty-six subjects were randomly allocated to
      the two treatment groups: the stabilization splint and the control splint group.
      After 10 weeks' treatment, the intensity of secondary otalgia, measured on a VAS
      scale (from 0 to 100 mm), decreased statistically significantly in the
      stabilization splint group (t 2.12; P 0.006), but not in the control group.
      Improvement in active TMD treatment need in subjects showing moderate or severe
      signs and symptoms of TMD was reported significantly more often in the
      stabilization splint group than in the control splint group (chi2 5.71; P.017). A
      statistically significant decrease in the Helkimo clinical dysfunction index was
      seen in the subjects with stabilization splint (Z-2.63; P.009), but not in the
      subjects with control splint. The results indicate that the use of a
      stabilization splint is beneficial with regard to secondary otalgia and active
      TMD treatment need.

PMID- 12222652
TI  - Pharmacokinetics and bioavailability of herbal medicinal products.
AB  - The use of herbs for treating various ailments dates back several centuries.
      Usually, herbal medicine has relied on tradition that may or may not be supported
      by empirical data. The belief that natural medicines are much safer than
      synthetic drugs has gained popularity in recent years and led to tremendous
      growth of phytopharmaceutical usage. Market driven information on natural
      products is widespread and has further fostered their use in daily life. In most
      countries there is no universal regulatory system that insures the safety and
      activity of phytopharmaceuticals. Evidence-based verification of the efficacy of
      HMPs (herbal medicinal products, botanicals) is still frequently lacking.
      However, in recent years, data on evaluation of the therapeutic and toxic
      activity of herbal medicinal products became available. The advances in
      analytical technology have led to discovery of many new active constituents and
      an ever-increasing list of putatively active constituents. Establishing the
      pharmacological basis for efficacy of HMPs is a constant challenge. Of particular
      interest is the question of bioavailability to assess to what degree and how fast
      compounds are absorbed after administration of HMPs. Of further interest is the
      elucidation of metabolic pathways (yielding potentially new active compounds),
      and the assessment of elimination routes and their kinetics. These data become an
      important issue to link data from pharmacological assays and clinical effects. Of
      interest are currently also interactions of herbal medicinal products with
      synthetically derived drug products. A better understanding of the
      pharmacokinetics and bioavailability of phytopharmaceuticals can also help in
      designing rational dosage regimens. In this review, pharmacokinetic and
      bioavailability studies that have been conducted for some of the more important
      or widely used phytopharmaceuticals are critically evaluated. Furthermore,
      various drug interactions are discussed which show that caution should be
      exercised when combining phytopharmaceuticals with chemically derived active
      pharmaceutical ingredients.

PMID- 12222653
TI  - The efficacy of a herbal medicine (Mao-to) in combination with intravenous
      natural interferon-beta for patients with chronic hepatitis C, genotype 1b and
      high viral load: a pilot study.
AB  - Patients with chronic hepatitis C, with a high serum viral load (> or = 1 Meq/ml)
      and genotype 1b seem to be resistant to interferon (IFN) therapy. To evaluate the
      efficacy of a herbal medicine (Mao-to) in combination with natural IFN-beta for
      the treatment of these patients, eighteen Japanese patients were enrolled in this
      study. Every patient received 6 million units (MU) of IFN-beta intravenously
      daily for 8 weeks. Mao-to was given orally 3-4 times a day during the IFN-beta
      administration, Sixteen of the 18 patients (89%) became negative for serum HCV
      RNA at the end of treatment, but only 2 of them (11%) remained negative for the
      virus RNA at 6 months of follow-up. Serum ALT levels normalized in 17 patients
      (94%) at 2 weeks of follow-up after the cessation of therapy, and 11 patients
      (61%) retained normal ALT levels for more than 6 months of follow-up. This rate
      of biochemical response was high as compared with that of therapy with IFN-beta
      alone (19%) in the largest IFN-beta trial in Japan. Serum hyaluronic acid levels
      were decreased significantly from 147.0 +/- 110.5 ng/ml to 77.4 +/- 67.4 ng/ml in
      the sustained biochemical response group (P = 0.003). None of the patients needed
      to interrupt therapy because of side effects of IFN-beta. Thus, Mao-to
      administration together with IFN-beta treatment could increase the sustained
      biochemical response rate, and reduce liver fibrosis.

PMID- 12222654
TI  - A comparative study between excess-dose users and regular-dose users of rhubarb
      contained in Kampo medicines.
AB  - With prolonged use of rhubarb-containing Kampo medicines, some patients come to
      ask for high-dose rhubarb because of deteriorated reactivity to rhubarb. We
      divided patients into two groups in terms of rhubarb-dose, and compared clinical
      backgrounds between regular-dose group and excess-dose group. Patients who were
      treated with rhubarb-containing Kampo extracts (manufactured prescriptions) or
      Kampo formulae (decoctions) for more than 12 months were enrolled. These two
      groups were compared for age, sex, shape of stool, abdominal symptoms, existence
      of hemorrhoids, Kampo diagnosis of abdomen, past stimulant laxative use, duration
      of stimulant laxative use before the first administration of rhubarb, duration of
      rhubarb use in our hospital, and initial existence of stimulant pain caused by
      taking stimulant laxatives for the first time. No significant difference was
      shown between the two groups in terms of age, duration of stimulant laxative-use
      before the first prescription of rhubarb, shape of stool, abdominal symptoms,
      existence of hemorrhoids, or duration of rhubarb-use. However, most patients in
      the regular-dose group had initial stimulant pain of the abdomen upon taking
      stimulant laxatives for the first time, but most patients in the excess-dose
      group did not (p < 0.001). All patients except one in the regular dose group had
      the sign of "umbilical region tenderness on pressure", but half of the excess
      dose group did not have it (p = 0.041). Based on these findings, the absence of
      "initial stimulant pain" and the absence of "umbilical region tenderness on
      pressure" may predict increasing or excess use of rhubarb, and long-term use of
      rhubarb should be discouraged more strongly in the patients without these signs.

PMID- 12222655
TI  - Therapeutic efficacy of Stephania tetrandra S. Moore for treatment of
      neovascularization of retinal capillary (retinopathy) in diabetes--in vitro
      study.
AB  - The present study was designed to examine therapeutic efficacy of the root
      extract of Stephania Tetrandra S. Moore (STMS) (traditional Chinese medicine; Han
      Fang Ji) for treatment of neovascularization of the retinal capillary
      (retinopathy) in streptozotocin (STZ)-induced diabetic rats (STZ diabetic rats)
      in culture. Recently we have established the culture system in which fetal bovine
      serum (FBS) in Dulbecco modified Eagle medium (DMEM) induced neovascularization
      of the retinal capillary and choroidal capillary in normal rats in culture. STZ
      diabetic rats showed more neovascularization of the retinal capillary and
      choroidal capillary than did normal rats in culture. In this study, the retinal
      tissue was removed for the posterior ocular region and cultured in DMEM
      containing FBS. The choroidal tissue of the posterior ocular region was also
      removed and cultured as an internal reference. Administration of STSM (0.91, 9.1
      and 91 microg/ml) significantly suppressed neovascularization of the retinal
      capillary in both STZ diabetic rats and normal rats in a dose-dependent manner.
      Similar results were obtained with the choroidal capillary; administration of
      STSM suppressed neovascularization of the choroidal capillary in both STZ
      diabetic rats and normal rats. In order to determine the component of STSM
      inhibiting neovascularization of the retinal capillary, tetrandrine (a major
      chemical constituent of STSM) was administered and neovascularization of the
      retinal capillary was examined in culture. The effect of tetrandrine on the
      choroidal capillary was also examined as an internal reference. Administration of
      tetrandrine (0.1, 1.0 and 10 microM) suppressed neovascularization of the retinal
      capillary in both STZ diabetic rats and normal rats in a dose-dependent manner.
      Similar results were obtained with the choroidal capillary of both STZ diabetic
      rats and normal rats. We infer, therefore, that STSM has a direct effect on the
      retinal capillary of posterior ocular region and suppresses neovascularization of
      retinal capillary in STZ diabetic rats through the activation of tetrandrine.
      These results suggest that STSM may prevent for delay the progression of
      retinopathy in diabetic patients.

PMID- 12222656
TI  - The effect of treatment with the medicinal plant Rhazya stricta decne on
      gentamicin nephrotoxicity in rats.
AB  - Generation of oxygen free radicals in kidney cortex plays an important role in
      the pathogenesis of gentamicin (GM) nephrotoxicity, and the leaf extract of the
      medicinal plant Rhazya stricta has been shown to have an anti-oxidant action in
      rats. Therefore, in the present work we aimed at testing, in this species, the
      possible protective effect of R. stricta extract on GM nephrotoxicity. Crude
      water extract of R. Stricta leaves (0.25, 0.5 and 1 g/Kg) was given orally to
      rats four days before GM treatment, and thereafter, concomitantly with GM (80
      mg/Kg/day) for another six days. Nephrotoxicity was evaluated histopathologically
      by light microscopy, and biochemically by measuring the concentrations of urea
      and creatinine in serum, reduced glutathione (GSH), lipid peroxidation and
      superoxide dismutase (SOD) activity in kidney cortex. The results suggested that
      the plant extract (0.25 g/Kg) was ineffective in significantly altering the
      indices of GM-induced nephrotoxicity. However, a dose-related amelioration in the
      indices of toxicity was noted when the two higher doses of the plant extract were
      given. The plant extract, at the three doses used, had no significant adverse
      effect on the body weight of treated rats or on the measured hepatic and renal
      functions in serum. However, the two higher doses, significantly and dose
      dependently increased SOD activity and GSH concentration, and decreased that of
      lipid peroxides in the kidney cortex. These results suggest that R. stricta water
      extract may contain compounds that could potentially ameliorate GM nephrotoxicity
      in rats.

PMID- 12222657
TI  - Immunological studies of Revitonil, a phytopharmaceutical containing Echinacea
      purpurea and Glycyrrhiza glabra root extract.
AB  - A phytopharmaceutical containing an extract of Echinacea purpurea and Glycyrrhiza
      glabra root (Revitonil tablets) was investigated for its suggested
      immunostimulating potential, using several in vitro tests and the in vivo carbon
      clearance model in mice. In the in vitro phagocytosis test with human
      granulocytes, Revitonil showed a 44-53% stimulating effect at a concentration of
      100 microg/ml. Whereas in the chemoluminescence test at a concentration of 1.25
      microg/ml, Revitonil tablets exhibited a moderate enhancing effect only, a
      remarkable stimulating activity (30-50%) was observed in the T-lymphocyte CD69
      bioassay at a concentration of 100 microg-1 microg/ml. The highest immunological
      efficacy could be assigned to Revitonil as revealed by the in vivo carbon
      clearance model in mice. With RCt/RCc-values of 2.0, Revitonil exhibited a very
      high carbon elimination rate at oral administration. Because the Echinacea and
      Glycyrrhiza monoextracts alone showed lower RCt/RCc-values (1.3-1.7) than
      Revitonil, a potentiating synergistic effect of the extract mixture in Revitonil
      can be postulated.

PMID- 12222658
TI  - Extractable polysaccharides of Panax quinquefolius L. (North American ginseng)
      root stimulate TNFalpha production by alveolar macrophages.
AB  - We have investigated the immunostimulatory activity of the medicinal plant Panax
      quinquefolius L. (North American ginseng). Rat alveolar macrophages were treated
      with different extracts from 4-year old roots, and tumour necrosis factor alpha
      (TNF) production was used as a measure of immunostimulatory activity. Aqueous
      extracts of P. quinquefolius root (1-100 microg/ml) were found to significantly
      stimulate alveolar macrophage TNF release. Both a P. quinquefolius methanol
      extract containing ginsenosides (but no polysaccharides), and pure ginsenoside
      Rb1, the major ginsenoside present in P. quinquefolius, were found to be inactive
      as TNF-stimulating agents. Significant TNF-stimulating activity was found in the
      extractable polysaccharide fraction, which was hydrolyzed and found to contain
      glucose, galactose, arabinose, rhamnose, and mannose. This represents the first
      evidence that North American ginseng exerts cytokine-stimulating activity on
      macrophages.

PMID- 12222659
TI  - Effect of salvianolic acids from Radix Salviae miltiorrhizae on regional cerebral
      blood flow and platelet aggregation in rats.
AB  - This study was conducted to observe the effect of salvianolic acids (SA) on
      regional cerebral blood flow (rCBF) in rats and on platelet aggregation in vitro
      and in vivo. Cerebral ischemia was produced in rats by occluding of the right
      middle cerebral artery, together with the right common carotid artery. rCBF was
      monitored by H2 clearance method with a tissue blood-flow meter. Platelet
      aggregation induced by collagen, ADP, and AA was measured in vitro and in vivo by
      platelet aggregometer. Doses of SA at 6 and 10 mg/kg body wt. (i.v.) improved
      rCBF in rats after ischemia, but had no obvious effect on normal rCBF. In vitro,
      SA inhibited significantly the platelet aggregation induced by collagen, ADP, and
      AA with IC50 values of 0.197, 2.22 and 3.29 x 10(3) mg/l, respectively. In vivo,
      doses of SA at 6 and 10 mg/kg body wt. inhibited significantly the platelet
      aggregation induced by collagen, and SA at 10 mg/kg body wt. inhibited remarkably
      platelet aggregation induced by ADP. The results suggest that SA could improve
      rCBF in the ischemic hemisphere and inhibit platelet aggregation in rats.

PMID- 12222660
TI  - PYCNOGENOL chewing gum minimizes gingival bleeding and plaque formation.
AB  - PYCNOGENOL is an antioxidant phytochemical shown to have antiinflammatory
      activity in both the in vitro and in vivo models. This study compared the effects
      of chewing gums with and without PYCNOGENOL on gingival bleeding and plaque
      formation in 40 human subjects. In this double-blind study, subjects were
      assigned randomly to receive either control gums without PYCNOGENOL or
      experimental gums containng 5 mg PYCNOGENOL. Subjects used chewing gums for 14
      days. Gingival bleeding and plaque scores were taken before and after the
      experiment. PYCNOGENOL chewing gums significantly reduced gingival bleeding,
      while no changes were noted in bleeding indexes in control subjects who used
      regular chewing gums. Subjects using regular control gums had significant
      increases of dental plaque accumulation during the two-week period. No increases
      in plaque accumulation were noted in subjects using PYCNOGENOL chewing gums. The
      data of this study suggest that the use of Pycnogenol chewing gums can minimize
      gingival bleeding and plaque accumulation.

PMID- 12222661
TI  - Effect of PYCNOGENOL on the toxicity of heart, bone marrow and immune organs as
      induced by antitumor drugs.
AB  - PYCNOGENOL is a mixture of water-soluble bioflavonoids extracted from the bark of
      pine trees growing in the southwest coastal region of France. In the present
      paper the effects of PYCNOGENOL (Pyc) on the toxicity of bone marrow, heart and
      immune organs induced by anticancer drugs were investigated, in mice. The
      following results were obtained: 1. Pyc at the orally-administered dose of 200
      and 150 mg/kg body wt. markedly prevented the elevation of serum creatine
      phosphokinase (CPK) activity and the decrease of heart rate in mice treated with
      doxorubicin (Dox); 2. Pyc at 100 and 150 mg/kg body wt. significantly antagonized
      the inhibition of DNA synthesis in thymus induced by subcutaneous injection of
      cyclophosphamide (Cyc); 3. Pyc at 150 and 200 mg/kg body wt. markedly induced
      increase of erythrocytes and hemoglobin, but had no effect on leukopenia, in Cyc
      treated mice; and 4. Pyc has no antagonizing effect on the anticancer activity of
      Dox and Cyc. All the results suggest that Pyc possesses a protective effect on
      the cardiotoxicity of Dox and the inhibition of thymus DNA synthesis induced by
      Cyc in mice.

PMID- 12222662
TI  - Studies on the antinociceptive, anti-inflammatory and anti pyretic effects of
      Isatis indigotica root.
AB  - The root of Isatis indigotica (Cruciferae), popularly known as Ban-Lan-Gen is
      used in traditional Chinese medicine for seasonal febrile diseases, pestilence,
      mumps, eruptive diseases, inflammatory diseases with redness of skin, sore
      throat, etc. In this study, we evaluated the antinociceptive, antiinflammatory
      and antipyretic effects of Isatis indigotica root methanolic extract. The results
      showed that Isatis indigotica root extract significantly and dose-dependently
      inhibited the writhing responses of mice and decreased the licking time in both
      the early and late phases of the formalin test. It also reduced the paw edema
      induced by carrageenan in rats. In addition, it potently attenuated pyrexia
      induced by lipopolysaccharide.

PMID- 12222663
TI  - Phytochemical analysis and analgesic properties of Curcuma zedoaria grown in
      Brazil.
AB  - The present study describes the phytochemical analysis and analgesic activity of
      Curcuma zedoaria rhizomes grown in Brazil. The results showed that the
      hydroalcoholic extract, fractions, specially dichloromethane, and a pure
      compound, denoted as curcumenol (1), exhibited potent and dose-related analgesic
      activity when evaluated in several models of pain in mice, including writhing,
      formalin and capsaicin. Compound (1), which seems to be the main active principle
      from this plant, presented promising analgesic effects, being several times more
      potent than different reference drugs evaluated in the same experimental models.
      The calculated ID50 values (micromol/kg, i.p) were 22 and 12 when evaluated in
      writhing and capsaicin tests, respectively, and 29 micromol/kg in relation to the
      second phase of the formalin model. The lack of effect in the hot plate test
      suggests that (1) act by a mechanism which do not involves the participation of
      the opioid system. The phytochemical analysis indicated that the chemical
      composition of the plant grown in Brazil is similar to that grown in other
      countries. The results confirm and justify the popular use of this plant for the
      treatment of dolorous processes.

PMID- 12222664
TI  - Preliminary evaluation of anti-inflammatory and anti-arthritic activity of S.
      lappa, A. speciosa and A. aspera.
AB  - Saussurea lappa, Argyreia speciosa and Achyranthes aspera are well known Indian
      medicinal plants used in the indigenous systems of medicine for the treatment of
      inflammatory conditions. The ethanolic extracts of the plants at the doses of 50,
      100 and 200 mg/kg, p.o. were screened for their effect on acute and chronic
      inflammation induced in mice and rats. S. lappa and A. speciosa were found to
      significantly inhibit paw edema induced by carrageenan and Freund's complete
      adjuvant and to prevent accumulation of inflammatory cells in carrageenan-induced
      peritonitis at doses of 50-200 mg/kg. A. aspera inhibited these inflammatory
      responses at doses of 100-200 mg/kg. The studies reveal that the ethanolic
      extracts of S. lappa, A. speciosa and A. aspera possess anti-inflammatory and
      anti-arthritic activity and support the rationale behind the traditional use of
      these plants in inflammatory conditions.

PMID- 12222665
TI  - The anti-allergic effects of Crinum glaucum aqueous extract.
AB  - The aqueous extract of Crinum glaucum was investigated for its effects on rat
      passive cutaneous anaphylactic reaction, rat peritoneal mast cell degranulation
      and allergic bronchoconstriction in the guinea pig. The extract demonstrated a
      significant (p < 0.05) reduction in area of dye leakage. The extract,
      administered for five days, inhibited mast cell degranulation of normal and
      passively sensitized rats induced by dextran and antigen. Allergic
      bronchoconstriction in actively sensitized guinea pigs was inhibited by the
      extract. The effects of the extract observed were comparable to those of sodium
      cromoglycate. These results substantiate the efficacy of the extract in the
      treatment of asthma, in traditional medicine.

PMID- 12222666
TI  - Evaluation of commercial Ginkgo biloba dietary supplements for the presence of
      colchicine by high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic method with photodiode array detection
      was developed for the detection of the presence of colchicine in commercial
      ginkgo products. The method is based on the baseline separation of constituents
      in ginkgo samples plus reference colchicine. The minimal detectable concentration
      of colchicine is 1.0 ng on column in the current assay. By analysis of retention
      time and UV profile of suspect peaks in the sample with those of reference
      colchicine, none of the nine commercial ginkgo products analyzed contained
      colchicine.

PMID- 12222667
TI  - Effects of Podophyllum hexandrum on radiation induced delay of postnatal
      appearance of reflexes and physiological markers in rats irradiated in utero.
AB  - Effect of 2.0 Gy gamma-dose delivered to rats in utero on 17th day of gestation
      was studied to monitor the radiation induced retardation of neurophysiological
      development in postnatal young ones. Rhizome of Podophyllum hexandrum which has
      been well documented for mitigating radiation injuries in adult mice was
      attempted for modifying radiation damage. Rats were observed from postnatal day 1
      to 25 for the age of the appearance of physiological markers (pinna detachment,
      inscisor's eruption, eye opening) and acquisition of reflexes (surface righting,
      visual placing, reflex suspension, negative geotaxis). In irradiated groups there
      was a significant weight reduction in mother rats and offsprings throughout the
      experimental period. There was radiation-induced delay in the appearance of pinna
      detachment but not in eye opening and inscisor's eruption. Appearance of the
      reflexes were also delayed due to irradiation. Preirradiation administration of
      the extract of Podophyllum hexandrum (i.p., 200 mg/kg/b.w.) mitigated radiation
      induced postnatal physiological alterations. These studies have implications in
      protection against damage (in utero) due to planned radiation exposure.

PMID- 12222668
TI  - Reduction of plasma triglyceride level and enhancement of plasma albumin
      concentration by Oren-gedoku-to administration.
AB  - Oren-gedoku-to (Huanglian-Jie-Du-Tang, OGT) has been used for the treatment of
      cerebrovascular disease, hypertension, gastritis and liver disease in Japan. The
      present study was to test whether ingestion of OGT extract (TJ-15) would affect
      the metabolism of fatty acids and the usual antioxidant molecule (such as
      albumin, uric acid and bilirubin) levels in human plasma. After the
      administration of TJ-15, plasma total cholesterol and the triglyceride level
      significantly decreased, and lipoprotein lipase mass increased. Significant
      enhancement of plasma albumin level and reduction of the total plasma protein
      level resulted in an increment of the albumin/globulin ratio. Plasma fibrinogen,
      an independent risk factor for cerebrovascular disease, declined considerably,
      but the reduction was not statistically significant. The findings of this study
      suggest that ingestion of TJ-15 improves the microcirculation through lipid and
      protein metabolisms, and is useful for the treatment of cerebral vascular attack
      in human.

PMID- 12222669
TI  - Analysis of thirteen populations of black cohosh for formononetin.
AB  - Black cohosh (Actaea racemosa L. syn. Cimicifuga racemosa (L.) Nutt.), a North
      American perennial plant, is a promising natural alternative to hormone
      replacement therapy for treating menopausal symptoms, but the mechanism of action
      is not understood. The clinical actions of this plant have been attributed to the
      isoflavonone formononetin since 1985, when its presence was reported in a black
      cohosh extract. Others have since looked for formononetin, but have not detected
      it. We looked for formononetin in extracts of black cohosh roots and rhizomes
      collected in thirteen locations in the eastern United States, including Maryland,
      New Jersey, New York, North Carolina, Pennsylvania, Virginia, and Tennessee. The
      rhizome samples were extracted using 80% methanol, and the extracts were
      partially purified using solid-phase extraction to concentrate any isoflavonoids
      that might be present. We tested for formononetin in these partially purified
      samples using thin-layer chromatography and high-performance liquid
      chromatography with a photodiode array detector and a mass spectrometer.
      Formononetin was not detected in any of the thirteen plant populations examined.
      Remifemin, a German product now on the United States market, and CimiPure, a
      commercially available black cohosh rhizome extract, were also analyzed. We did
      not detect formononetin, or ononin (formononetin-7-glucoside), in any sample
      tested by the above-mentioned chemical analyses. Therefore, the clinically
      observed estrogen-like actions of black cohosh, such as reduction of hot flashes,
      are likely due to a compound, or combination of compounds, other than
      formononetin.

PMID- 12222670
TI  - Clinical trials with hypericum extracts in patients with depression--results,
      comparisons, conclusions for therapy with antidepressant drugs.
AB  - By the spring of 2002, results from 34 controlled, double-blind trials of
      Hypericum extracts in some 3000 patients, predominantly with mild to moderate
      forms of depression, had been published. An overview is given of the studies
      conducted since 1990. In the majority of them, the efficacy criterion (primary
      endpoint) was the score and/or response rate on the Hamilton Rating Scale of
      Depression (HAMD). In ten studies, based on extracts prepared with 50% or 60%
      ethanol in water (V/V), the dosages ranged from 300 mg to 1050 mg of extract per
      day. Five of the ten studies were placebo-controlled and in all five cases, the
      Hypericum extract was shown to be significantly superior. Results with Hypericum
      were as good or even better than with imipramine or fluoxetine. In the period
      since 1990, a total of twelve controlled trials have been published with one
      particular extract prepared with 80% methanol in water (V/V), of which six were
      placebo-controlled, two compared Hypericum with imipramine and one each with
      maprotiline, amitriptyline, sertraline or light therapy. Dosages ranged from 450
      1200 mg extract per day. Statistical analysis of the total Hamilton scores showed
      significant differences between Hypericum extract and placebo in four of the six
      placebo-controlled studies and a trend in favour of the active treatment in the
      other two. Of the five comparative trials against four different synthetic
      antidepressants, amitriptyline was significantly superior to Hypericum after six
      weeks of therapy, whilst there were no significant differences in treatment
      outcome between Hypericum and the other synthetics in the remaining four studies.
      The results of the trials conducted to date show no major differences in efficacy
      of the alcoholic extracts. Taking all the results into account, it can be assumed
      that the threshold dose for efficacy against individual symptoms and complaints
      that occur in the course of the depressive illness could be about 300 mg of
      extract per day. In the medically supervised treatment of mild to moderate
      depression, doses of approximately 500-1000 mg of extract per day of these
      preparations of St. John's Wort are of comparable efficacy to synthetic
      antidepressants in their normally prescribed dosages.

PMID- 12222671
TI  - Effects of Citrus aurantifolia concentrated extract on the spontaneous
      proliferation of MDA-MB-453 and RPMI-8866 tumor cell lines.
AB  - The in vitro effects of concentrated lime juice (CLJ) extract on the spontaneous
      proliferation of a human breast carcinoma cell line (MDA-MB-453) and a human
      lymphoblastoid B cell line (RPMI-8866) were investigated. CLJ extract was
      prepared by freeze-drying fresh fruit juice and dialyzing the concentrated
      extract against phosphate buffered saline in order to deplete low molecular
      weight micronutrients such as flavonoids as well as adjusting the pH of the
      extract to the physiological range. The effects of different concentrations of
      the CLJ extract on the spontaneous proliferative responses of the cell lines were
      determined by 3H-thymidine incorporation after 24 hrs of incubation. CLJ extract
      had no significant effect on MDA-MB-453 cell line, however, using the
      concentrations of 125, 250, and 500 microg/ml of CLJ extract a significant
      inhibition of the spontaneous proliferation of RPMI-8866 cell line was detected
      (P < 0.05). Due to the protein nature of the biologically active macromolecules
      of the CLJ extract (Gharagozloo and Ghaderi, 2001), it is reasonable to assume
      that the protein components of the CLJ extract may have anti-proliferative
      effects on tumor cell lines.

PMID- 12222672
TI  - Stroke therapy in traditional Chinese medicine (TCM): prospects for drug
      discovery and development.
AB  - Brain injuries resulting from stroke are a major and increasing public health
      problem in both developed and developing countries worldwide. China's extensive
      experience in the use of traditional Chinese medicines (TCMs) in stroke therapy
      indicates that TCM preparations are effective, with few or no side-effects. There
      are more than 100 traditional medicines in use for stroke therapy in China. Some
      of their therapeutic effects in stroke have been confirmed by recent clinical
      studies. A large number of compounds have been isolated from TCMs and most of
      these resources have not yet been characterized for pharmacological purposes.
      Here, this article explains how TCM provides an extensive and knowledge-rich
      foundation for implementing a strategically focused pharmacological research
      program aimed at the development of new drugs.

PMID- 12222673
TI  - E/S/C/O/P--the European Scientific Cooperative on Phytotherapy.

PMID- 12222674
TI  - Reconstitution of transport-active multidrug resistance protein 2 (MRP2; ABCC2)
      in proteoliposomes.
AB  - The apical multidrug resistance protein MRP2 (symbol ABCC2) is an ATP-dependent
      export pump for anionic conjugates in polarized cells. MRP2 has only 48% amino
      acid identity with the paralog MRP1 (ABCC1). In this study we show that purified
      recombinant MRP2 reconstituted in proteoliposomes is functionally active in
      substrate transport. The Km values for ATP and LTC4 in the transport by MRP2 in
      proteoliposomes were 560 microM and 450 nM, respectively. This transport function
      of MRP2 in proteoliposomes was dependent on the amount of MRP2 protein present
      and was determined to 2.7 pmol x min(-1) x mg MRP2(-1) at 100 nM LTC4. Transport
      was competitively inhibited by the quinoline derivative MK571 with 50% inhibition
      at about 12 microM. Our data document the first reconstitution of transport
      active purified recombinant MRP2. Binding and immunoprecipitation experiments
      indicated that MRP2 preferentially associates with the chaperone calnexin, but co
      reconstitution studies using purified MRP2 and purified calnexin in
      proteoliposomes suggested that the LTC4 transport function of MRP2 is not
      dependent on calnexin. The purified, transport-active MRP2 may serve to identify
      additional interacting proteins in the apical membrane of polarized cells.

PMID- 12222676
TI  - Analysis of the prion protein in primates reveals a new polymorphism in codon 226
      (Y226F).
AB  - Bovine spongiform encephalopathy has been epizootic in cows for the last two
      decades, and most probably causes variant Creutzfeldt-Jakob disease in humans. A
      thorough understanding of prion pathogenesis relies on suitable animal models.
      Modeling the transmission of BSE to primates is a crucial public health priority,
      necessary for determining the tissue distribution of the agent and for devising
      therapies. Susceptibility of humans to BSE is partly determined by polymorphism
      within the gene encoding the cellular prion protein, Prnp, a fact that must be
      taken into account in primate studies. However, no information is available on
      Prnp polymorphisms in primates. We have sequenced the Prnp open reading frames of
      30 non-consanguineous Rhesus macaques. All macaques were homozygous for
      methionine at codon 129, which is polymorphic in humans and seems to modulate
      prion susceptibility. However, we identified a novel polymorphism in macaque
      Prnp, localized on codon 226 (Y226F). A modulatory effect of this polymorphism on
      the development of prion disease is possible because codon 226 is close to the
      suggested binding side of the factor X, which has been invoked as a determinant
      of the prion species barrier.

PMID- 12222675
TI  - Processing of the human transferrin receptor at distinct positions within the
      stalk region by neutrophil elastase and cathepsin G.
AB  - The ectodomain of the human transferrin receptor (TfR) is released as soluble TfR
      into the blood by cleavage within a stalk. The major cleavage site is located C
      terminally of Arg-100; alternative cleavage sites are also present. Since the
      cleavage process is still unclear, we looked for proteases involved in TfR
      ectodomain release. In the supernatant of U937 histiocytic cells we detected
      alternatively cleaved TfR (at Glu-110). In membrane fractions of these cells we
      identified two distinct proteolytic activities responsible for TfR cleavage
      within the stalk at either Val-108 or Lys-95. Both activities could be inhibited
      by serine protease inhibitors, but not by inhibitors of any other class of
      proteases. Protein purification yielded a 28 kDa protein that generated the Val
      108 terminus. The protease activity could be ascribed to neutrophil elastase
      according to the substrate specificity determined by amino acid substitution
      analysis of synthetic peptides, an inhibitor profile, the size of the protease
      and the use of specific antibodies. The results of analogous experiments suggest
      that the second activity is represented by another serine protease, cathepsin G.
      Thus, membrane-associated forms of neutrophil elastase and cathepsin G may be
      involved in alternative TfR shedding in U937 cells.

PMID- 12222677
TI  - Highlight: Environmental mutagenesis.

PMID- 12222678
TI  - DNA double-strand break repair by homologous recombination.
AB  - The induction of double-strand breaks (DSBs) in DNA by exposure to DNA damaging
      agents, or as intermediates in normal cellular processes, constitutes a severe
      threat for the integrity of the genome. If not properly repaired, DSBs may result
      in chromosomal aberrations, which, in turn, can lead to cell death or to
      uncontrolled cell growth. To maintain the integrity of the genome, multiple
      pathways for the repair of DSBs have evolved during evolution: homologous
      recombination (HR), non-homologous end joining (NHEJ) and single-strand annealing
      (SSA). HR has the potential to lead to accurate repair of DSBs, whereas NHEJ and
      SSA are essentially mutagenic. In yeast, DSBs are primarily repaired via high
      fidelity repair of DSBs mediated by HR, whereas in higher eukaryotes, both HR and
      NHEJ are important. In this review, we focus on the functional conservation of HR
      from fungi to mammals and on the role of the individual proteins in this process.

PMID- 12222679
TI  - An overview of the analysis of DNA methylation in mammalian genomes.
AB  - DNA methylation at position C5 of the pyrimidine ring of cytosine in mammalian
      genomes has received a great deal of research interest due to its importance in
      many biological phenomena. It is associated with events such as epigenetic gene
      silencing and the maintenance of genome integrity. Aberrant DNA methylation,
      particularly that of chromosomal regions called CpG islands, is an important step
      in carcinogenesis. In order to elucidate methylation profiling of complex
      genomes, various methods have been developed. Many of these methods are based on
      the differential reactivity of cytosine and 5-methylcytosine to various
      chemicals. The combined use of these chemical reactions and other preexisting
      methods has enabled the discrimination of cytosine and 5-methylcytosine in
      complex genomes. The use of proteins that preferentially bind to methylated DNA
      has also successfully been used to discriminate between methylated and
      unmethylated sites. The chemical and structural dissection of the in vivo
      processes of enzymatic methylation and the binding of methyl-CpG binding proteins
      provides evidence for the complex mechanisms that nature has acquired. In this
      review we summarize the methods available for the discrimination between cytosine
      and 5-methylcytosine in complex genomes.

PMID- 12222680
TI  - Methylation of the RASSF1A gene in human cancers.
AB  - Loss of genetic material from chromosome 3p21.3 is one of the most common and
      earliest events in the pathogenesis of lung cancer and many other solid tumors.
      The chromosomal area 3p21.3 is thought to harbor at least one important tumor
      suppressor gene, which, despite many years of investigation, has remained
      elusive. In our previous studies, we have identified and cloned a gene from the
      common homozygous deletion area at 3p21.3. The gene, named RASSF1A (Ras
      ASSociation domain Family 1A), has homology to a mammalian Ras effector. The
      RASSF1A gene is epigenetically inactivated in a large percentage of human lung
      cancers, in particular small cell carcinomas. A high frequency of methylation of
      RASSF1A is found also in breast cancers, renal cell carcinomas, ovarian, gastric
      and bladder cancers, and in neuroblastomas. The RASSF1A gene is a candidate for a
      tumor suppressor gene in 3p21.3.

PMID- 12222681
TI  - Exocyclic DNA adducts as oxidative stress markers in colon carcinogenesis:
      potential role of lipid peroxidation, dietary fat and antioxidants.
AB  - Molecular pathways to colorectal cancer involve multiple genetic changes, whereby
      extensive oxyradical damage causes mutations in cancer-related genes and leads to
      a cycle of cell death and regeneration. Besides direct oxidative DNA-damage,
      reactive oxygen and nitrogen species can induce etheno (epsilon)-DNA adducts
      mainly via trans-4-hydroxy-2-nonenal, generated as the major aldehyde by lipid
      peroxidation (LPO) of omega-6 PUFAs. Patients with familial adenomatous polyposis
      (FAP) develop multiple colorectal adenomas. In affected tissues increased LPO
      could be triggered due to increased arachidonic acid metabolism as a result of
      elevated cyclooxygenases. Our studies demonstrated an increased epsilon-DNA
      adduct level in affected colon epithelia of FAP patients. Epsilon-DNA adducts are
      promutagenic and can cause genomic instability that drives colorectal adenoma to
      malignancy. We have further investigated the potential chemopreventive properties
      of olive oil and its polyphenolic components. 'Mediterranean diet', of which
      olive oil is a major fatty acid source, has protective effects against human
      breast and colorectal cancers. Olive oil extracts and the newly identified lignan
      fractions showed high antioxidant capacity in vitro. As epsilon-DNA adducts are
      biomarkers for oxidative stress and LPO induced DNA damage, they can verify the
      efficacy of newly identified antioxidants, e.g. from olive oil, as
      chemopreventive agents against colon carcinogenesis.

PMID- 12222682
TI  - DNA polymorphisms as modulators of genotoxicity and cancer.
AB  - Cancer arises as a result of several factors, including multiple genes and
      environmental exposures. It is generally accepted that genetic polymorphisms are
      associated with most common disorders like cancer. The majority of polymorphisms
      are single nucleotide polymorphisms (SNPs) which occur with a frequency of 10(
      6). Susceptibility-conferring alleles are not sufficient to cause disease, but
      modulate the risk in combination with other alleles and environmental exposures,
      except in the extreme case of Mendelian cancer syndromes (e.g. FAP, HNPCC, Rb).
      The Environmental Genome Project identifies, among others, two lines of research
      along which we have been working and are the topic of the present paper, namely
      (i) allele-disease associations and (ii) functional studies of allelic variants.
      Case-control association studies conducted by us and others showed that
      polymorphism at a single site could increase risk-predictability by a factor < 2.
      It is known, however, that the individual risk predictability increases by
      associating multiple genetic polymorphisms as was demonstrated for breast, renal
      and thyroid cancer. Functional genomics of the putative susceptibility-alleles
      involved in cancers can improve substantially the strength of association
      studies. This calls for cell-systems capable of tracking different gene
      activities, which may clarify the possible role of allelic variants in certain
      cancers. This endeavour is likely to be met by the bacterial tester strain, MTC,
      described here.

PMID- 12222684
TI  - The bacterial regulatory protein H-NS--a versatile modulator of nucleic acid
      structures.
AB  - The small DNA binding protein H-NS is attracting broad interest for its profound
      involvement in the regulation of bacterial physiology. It is involved in the
      regulation of many genes in response to a changing environment and functions in
      the adaptation to many different kinds of stress. Many H-NS-controlled genes,
      including the hns gene itself, are further linked to global regulatory networks.
      H-NS thus plays a key role in maintaining bacterial homeostasis under conditions
      of a rapidly changing environment. In this review we summarize recent results
      from combined biochemical and biophysical efforts which have yielded new insights
      into the three-dimensional structure and function of H-NS. The protein consists
      of two distinct domains separated by an unstructured linker region, and the
      structural details available today have helped to understand how these domains
      may interact with each other or with ligand molecules. Functional studies have,
      in addition, revealed mechanistic clues for the various H-NS activities, like
      temperature- or growth phase-dependent regulation. Important elements for the
      specific regulatory activities of H-NS comprise different modes of DNA binding,
      protein oligomerization, the competition with other regulators and the fact that
      the topology of the target DNA is modulated during complex formation. The
      distinctive ability to recognize nucleic acid structures in combination with
      other proteins also explains H-NS-dependent post-transcriptional activities where
      the interaction with defined RNA structures and the interference with RNA/protein
      complexes during mRNA translation are crucial for regulation. Thus,
      protein/protein interactions, in combination with the recognition and modulation
      of nucleic acid structures, are key elements of the different mechanisms which
      make H-NS such a versatile regulator.

PMID- 12222683
TI  - Recent aspects of oxidative DNA damage: guanine lesions, measurement and
      substrate specificity of DNA repair glycosylases.
AB  - This review discusses recent aspects of oxidation reactions of DNA and model
      compounds involving mostly OH radicals, one-electron transfer process and singlet
      oxygen (1O2). Emphasis is placed on the formation of double DNA lesions involving
      a purine base on one hand and either a pyrimidine base or a 2-deoxyribose moiety
      on the other hand. Structural and mechanistic information is also provided on
      secondary oxidation reactions of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo),
      a major DNA marker of oxidative stress. Another major topic which is addressed
      here deals with recent developments in the measurement of oxidative base damage
      to cellular DNA. This has been mostly achieved using the accurate and highly
      specific HPLC method coupled with the tandem mass spectrometry detection
      technique. Interestingly, optimized conditions of DNA extraction and subsequent
      work-up allow the accurate measurement of 11 modified nucleosides and bases
      within cellular DNA upon exposure to oxidizing agents, including UVA and ionizing
      radiations. In addition, the modified comet assay, which involves the use of
      bacterial DNA N-glycosylases to reveal two main classes of oxidative base damage,
      is applicable to isolated cells and is particularly suitable when only small
      amounts of biological material are available. Finally, recently available data on
      the substrate specificity of DNA repair enzymes belonging to the base excision
      pathways are briefly reviewed.

PMID- 12222685
TI  - Molecular mechanisms of nickel carcinogenesis.
AB  - A brief review of the molecular mechanisms of nickel carcinogenesis is presented.
      Molecular mechanisms of nickel carcinogenesis are considered from the point-of
      view of nickel-induced gene silencing by DNA hypermethylation in mammalian cells
      and by its ability to inhibit histone acetylation. Model systems designed to
      study the molecular mechanism of gene silencing are discussed.

PMID- 12222686
TI  - DNA binding properties of the yeast Msh2-Msh6 and Mlh1-Pms1 heterodimers.
AB  - We describe here our recent studies of the DNA binding properties of Msh2-Msh6
      and Mlh1-Pms1, two protein complexes required to repair mismatches generated
      during DNA replication. Mismatched DNA binding by Msh2-Msh6 was probed by
      mutagenesis based on the crystal structure of the homologous bacterial MutS
      homodimer bound to DNA. The results suggest that several amino acid side chains
      inferred to interact with the DNA backbone near the mismatch are critical for
      repair activity. These contacts, which are different in Msh2 and Msh6, likely
      facilitate stacking and hydrogen bonding interactions between side chains in Msh6
      and the mismatched base, thus stabilizing a kinked DNA conformation that permits
      subsequent repair steps coordinated by the Mlh1-Pms1 heterodimer. Mlh1-Pms1 also
      binds to DNA, but independently of a mismatch. Mlh1-Pms1 binds short DNA
      substrates with low affinity and with a slight preference for single-stranded
      DNA. It also binds longer duplex DNA molecules, but with a higher affinity
      indicative of cooperative binding. Indeed, imaging by atomic force microscopy
      reveals cooperative DNA binding and simultaneous interaction with two DNA
      duplexes. The novel DNA binding properties of Mlh1-Pms1 may be relevant to signal
      transduction during DNA mismatch repair and to recombination, meiosis and
      cellular responses to DNA damage.

PMID- 12222687
TI  - N-hydroxyarylamine O-acetyltransferase-deficient Escherichia coli strains are
      resistant to the mutagenicity of nitro compounds.
AB  - In Salmonella typhimurium, a single enzyme catalyzes both the acetyl CoA
      dependent O-acetylation of hydroxylamines (a key step in the activation of
      mutagenic nitroaromatic compounds and related aromatic and heterocyclic amines)
      and the N-acetylation of aromatic amines. S. typhimurium Ames test mutants
      lacking this activity are highly resistant to the genotoxic effects of nitro
      compounds. However, such mutants have not yet been obtained in Escherichia coli.
      We used a PCR-based method to engineer a null mutation (deletion) of the nhoA
      gene encoding the enzyme in E. coli and we transduced this mutation into a lacZ
      strain background suitable for use in mutation assays. In E. coli, as in S.
      typhimurium, nhoA mutants show marked resistance to nitro compound mutagenicity.
      The new strains provide a clean background for expression of recombinant N
      acetyltransferases.

PMID- 12222688
TI  - Functional genomics of C190T single nucleotide polymorphism in human N
      acetyltransferase 2.
AB  - N-acetyltransferase 2 (NAT2) catalyzes N-acetylation and O-acetylation of many
      drugs and environmental carcinogens. Genetic polymorphisms in the NAT2 gene have
      been associated with differential susceptibility to cancers and drug toxicity
      from these compounds. Single nucleotide polymorphisms (SNPs) have been identified
      in the human NAT2 coding region. A new allele, NAT2*19, possessing the C190T
      (R64W) exchange, was recently identified. In order to understand the effect of
      this new SNP, recombinant NAT2*4 (reference) and NAT2*19 were expressed in yeast
      (Schizosaccharomyces pombe). The C190T (R64W) SNP in NAT2*19 caused substantial
      reduction in the NAT2 protein level and stability, but did not cause significant
      reduction in transformation efficiency or mRNA level. The enzymatic activities
      for N-acetylation of two arylamine carcinogens (2-aminofluorene, 4
      aminobiphenyl), and a sulfonamide drug (sulfamethazine) were over 100-fold lower
      for NAT2 19 compared to reference NAT2 4. Kinetic studies showed a reduction in
      Vmax but no significant change in substrate Km. In addition, the SNP caused
      significant reduction in the O-acetylation of the N-hydroxy-2-amino-1-methyl-6
      phenylimidazo [4,5-b] pyridine. These results show that NAT2*19 possessing the
      C190T (R64W) SNP encodes a slow acetylator phenotype for both N- and O
      acetylation, due to a reduction in the amount and stability of the NAT2 19
      allozyme.

PMID- 12222689
TI  - Increase in ceramide level alters the lysosomal targeting of cathepsin D prior to
      onset of apoptosis in HT-29 colon cancer cells.
AB  - Ceramide has been suggested as an important mediator of apoptosis. In HT-29
      colorectal cancer cells increased ceramide levels, induced by exogenous N
      acetylsphingosine (NAS, also known as C2-ceramide) or by 1-phenyl-2
      (decanoylamino)-3-morpholino-1-propanol (PDMP), inhibited the transport and
      processing of cathepsin D (CD), a lysosomal protease implicated in apoptosis of
      tumour cells. C2-dihydroceramide (DH-C2), an inactive analogue of NAS, had no
      effect on CD transport and maturation. The treatment with either NAS or PDMP was
      revealed to be cytotoxic for HT-29 cells and led to cell death with classical
      features of apoptosis. Morphological signs of apoptosis and DNA fragmentation
      became apparent only between 24 and 48 h of incubation and poly(ADP ribose)
      polymerase cleavage, a hallmark of caspase 3 activity, occurred no earlier than 8
      h from incubation. Secretion of proCD was almost abolished and the formation of
      double-chain mature CD was reduced and delayed by NAS, whereas PDMP largely
      inhibited the lysosomal targeting and maturation of proCD. NAS- and PDMP-induced
      alteration of proCD transport and maturation were apparent already 2 h after
      incubation with the drugs, which is much earlier than when classical biochemical
      and morphological evidence of apoptosis could be detected. These data indicate
      that alteration of CD (and possibly of other glycoproteins) transport along the
      secretory pathway due to increased levels of cell-associated ceramide is an early
      event in cells undergoing apoptosis.

PMID- 12222690
TI  - Is the Mediterranean diet especially beneficial for women? On the sex ratio of
      mortality.

PMID- 12222691
TI  - Effects of calcium channel blockers on atherosclerosis: new insights.
AB  - Atherosclerotic disease is the most frequent cause of death in the western world.
      The key role of calcium ions in atherogenesis has created interest in the
      antiatherogenic potential of calcium channel blockers. Nifedipine, administered
      in a long-acting gastrointestinal transport system (GITS) formulation, was shown
      to have similar efficacy to the diuretic co-amilozide in the International
      Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment
      (INSIGHT). Two side-arm studies of INSIGHT suggest that nifedipine GITS has a
      greater antiatherosclerotic effect than diuretic therapy, which may signal
      additional cardiovascular protection in the long term. This paper reviews the
      evidence for the antiatherogenic properties of calcium channel blockers and
      discusses their clinical implication.

PMID- 12222692
TI  - Effect of haemodialysis on left atrial mechanical function in patients with
      chronic renal failure.
AB  - OBJECTIVE: The aim of this study was to investigate the potential effects of
      haemodialysis on left atrial (LA) mechanical functions in patients with chronic
      renal failure. METHODS: Thirty-two patients with chronic renal failure (mean age
      42.8 +/- 19.6 years) were included in this study. LA volumes were determined
      echocardiographically at the time of mitral valve opening (maximal,Vmax), at the
      onset of atrial systole (p wave at the electrocardiography = Vp) and at the
      mitral valve closure (minimal, Vmin) according to the biplane area-length method
      in apical 4-chamber and 2-chamber view. All volumes were corrected to the body
      surface area, and the following left atrial emptying functions were calculated.
      LA passive emptying volume = Vmax - Vp, LA passive emptying fraction = LA passive
      emptying volume/Vmax. Conduit volume = LV stroke volume-(Vmax - Vmin), LA active
      emptying volume = Vp Vmin. LA active emptying fraction = LA active emptying
      volume/Vp, LA total emptying volume = (Vmax - Vmin), LA total emptying fraction =
      LA total emptying volume/Vmax. RESULTS: Mean fluid removal was 1,875 +/- 812
      milliliter. There was no difference between in the LA passive emptying volume
      before and after dialysis (10.83 +/- 7.44 vs. 11.47 +/- 7.73 cm3/m2, p > 0.05).
      Conduit volume (from 15.30 +/- 10.68 to 10.31 +/- 6.83 cm3/m2, p < 0.05), LA
      active emptying volume (from 12.61 +/- 6.39 to 9.25 +/- 4.40 cm3/m2, p < 0.005),
      LA total emptying volume (from 23.44 +/- 8.52 to 20.72 +/- 8.58 cm3/m2, p <
      0.05), LA maximal volume (from 39.44 +/- 14.07 to 28.89 +/- 11.80 cm3/m2, p <
      0.001), LA minimal volume (from 15.99 +/- 9.70 to 8.17 +/- 4.52 cm3/m2, p <
      0.001), and the volume at the onset of atrial systole (from 28.61 +/- 10.36 to
      17.42 +/- 7.20 cm3/m2, p < 0.001) decreased significantly after the haemodialysis
      session, whereas LA passive emptying fraction (from 0.27 +/- 0.14 to 0.38 +/-
      0.14%, p < 0.001), LA active emptying fraction (from 0.46 +/- 0.18 to 0.53 +/-
      0.17%, p < 0.05), LA total emptying fraction (from 0.61 +/- 0.14 to 0.72 +/-
      0.09%, p < 0.001) increased significantly after haemodialysis. CONCLUSION: The
      results of this study suggest that left atrial mechanical functions improve after
      haemodialysis in patients with chronic renal failure.

PMID- 12222693
TI  - Frequency of cardiac troponin-t elevation after successful direct stenting.
AB  - Direct stenting (stenting without balloon predilation) is a novel approach in
      percutaneous treatment of coronary artery lesions. This approach may also
      significantly lower the rate of procedural ischaemic complications by reducing
      aggression to the vessel wall and immediately sealing the dissections created due
      to balloon inflation by the endoprosthesis. However, the incidence of minor
      myocardial infarction after direct stenting is unknown. The purpose of this study
      was to measure cTnT, creatine kinase and its isoform, CK-MB after apparently
      successful elective stent implantation without balloon predilation. Enzyme levels
      were measured just before and 16 hours after the procedures. A second-generation
      commercial ELISA cTnT assay (Boehringer Mannheim Corporation) was used to measure
      cTnT with a cutoff of 0.1 ng/dl. There was no abnormality in all three enzymes
      before the procedure. CTnT was elevated in 6 patients (13.6%), CK and CK-MB were
      elevated in 1 (2.3%) patient at 16 hours after the procedure. Both CK and CK-MB
      elevation were observed in the patient with side branch occlusion. In all others
      cTnT measurements in addition to CK-MB measurements are needed to detect this
      minor myocardial damage. To the best of our knowledge this is the first report
      evaluating the incidence of myocardial injury after direct stenting. Direct
      stenting by avoiding balloon-induced complications may decrease procedural
      myocardial necrosis. Randomized studies with larger patient populations should be
      conducted to compare this approach with conventional stenting. CTnT measurements
      in addition to CKMB measurements are essential in detecting this minor myocardial
      damage.

PMID- 12222694
TI  - Angiotensin-converting enzyme gene polymorphism and coronary heart disease in
      Turkish type 2 diabetic patients.
AB  - OBJECTIVE: It has been suggested that the insertion (I)/deletion (D) polymorphism
      of the angiotensin-converting enzyme (ACE) may be associated with
      atherosclerosis. The aim of the study was to examine the association between ACE
      gene polymorphism and coronary heart disease in Turkish type 2 diabetic patients.
      METHODS AND RESULTS: A total of 152 (97 female, 55 male) type 2 diabetic patients
      were included into the study. All patients underwent myocardial perfusion
      scintigraphic examination and forty-five of them with a perfusion defect
      underwent coronary angiography.Thirty-eight patients with a coronary stenosis of
      more than 50% on coronary angiography were considered as having coronary heart
      disease. The I/D polymorphism was determined by polymerase chain reaction. There
      was no statistically significant difference in genotypic and allelic frequencies
      of the ACE I/D polymorphism among patients with and without coronary heart
      disease (DD:ID:II (%), 32:58:11 and 39:44:17, respectively). CONCLUSIONS: ACE
      gene polymorphism is not a significant parameter to determine coronary heart
      disease in Turkish type 2 diabetic patients.

PMID- 12222695
TI  - Hyperosmolar hyperglycaemic nonketotic coma associated with acute myocardial
      infarction: report of three cases.
AB  - Diabetes mellitus is one of the most commonly associated diseases of patients
      suffering an acute myocardial infarction. Although the coexistence of acute
      myocardial infarction with other clinical manifestations of diabetes have been
      well described, extremely few data exists about the concomitant occurrence of
      hyperosmolar hyperglycaemic nonketotic coma and myocardial infarctions. This
      article presents three patients with this association and aimed to discuss the
      clinical course and treatment strategies of this rare condition.

PMID- 12222696
TI  - Persistent ductus arteriosus in the adult: clinical features and experience with
      percutaneous closure.
AB  - Persistent ductus arteriosus in the adult carries a risk for becoming symptomatic
      with dyspnoea or palpitations, developing infective endarteritis, and finally for
      developing pulmonary hypertension with ensuing heart failure morbidity and
      mortality. Surgical closure is considered more and more to be outdated as first
      choice treatment since percutaneous closure is a safe and effective alternative.
      Only the Eisenmenger syndrome remains a clear contra-indication for closure,
      whether surgical or interventional. We report on our own experience in nine
      patients with persistent ductus arteriosus including eight cases who underwent
      percutaneous closure and one patient with Eisenmenger syndrome. In addition, our
      experience with clinical features and therapeutic modalities is related to the
      literature.

PMID- 12222697
TI  - Ischaemic preconditioning reduces spinal cord injury in transient ischaemia.
AB  - OBJECTIVE: Paraplegia remains a devastating complication after thoracic and
      thoracoabdominal aortic surgery for coarctations, dissections or aneurysms. Since
      the advent of ischaemic preconditioning of the myocardium, attention has been
      directed to the nervous system. This study was designed to evaluate the acute
      protective effect of ischaemic preconditioning on the spinal cord. MEDHODS AND
      RESULTS: Thirty-six New Zealand white rabbits were randomly assigned to one of
      three groups. The preconditioning group had 5 minutes of aortic occlusion, 25
      minutes reperfusion and 20 minutes of ischaemia, whereas the controls had only 20
      minutes of ischaemia. The sham group was anaesthetized and subjected to
      laparotomy without aortic occlusion. Physiological parameters and somatosensory
      evoked potentials were monitored during the experiment. Neurological outcome was
      clinically evaluated up to 48 hour after ischaemia and motor function was scored.
      Then the animals were sacrificed. Their spinal cord, abdominal aorta and its
      branches were removed and processed for histopathological examination.
      Histhopathological changes of the gray matter in the lumbosacral segments were
      scored from 0 to 6 according to a semi-quantitative scala. The changes in
      amplitudes of evoked potentials during ischaemia and recovery periods were
      similar in preconditioning and control groups. The average motor function score
      was significantly higher in the preconditioning group than the control group at
      24 and 48 hours after the ischaemic event (p < 0.05). Histological observations
      were consistent with the neurological findings. The histopathological scores in
      the control group and the preconditioning group were 3.2 (1.4-5.2) and 2.4 (0.8
      4.4), respectively (p < 0.05). CONCLUSIONS: The results suggest that ischaemic
      preconditioning reduces the spinal cord injury and improves neurological outcome
      in transient ischaemia in rabbits. This protective mechanism is rapidly invoked
      within only 25 minutes interval between the preconditioning stimulus and the
      ischaemic insult.

PMID- 12222698
TI  - Biventricular pacing and persistent left superior vena cava. Case report and
      review of the literature.
AB  - Persistent left superior vena cava is usually asymptomatic and does not cause any
      physiological problems (1). However it can severely complicate pacemaker
      implantation and render it sometimes impossible (2). In this case report we
      describe the implantation of a biventricular pacemaker using a left-sided
      approach in a patient with persistent left superior vena cava syndrome. A
      biventricular resynchronization device was used because of the reported
      beneficial haemodynamic effects of this pacing mode in patients with severe heart
      failure (3).

PMID- 12222700
TI  - Early use of pravastatin in patients with acute myocardial infarction undergoing
      coronary angioplasty.
AB  - AIM: To determine whether statin therapy initiated early in acute myocardial
      infarction together with thrombolytic therapy in patients with acute myocardial
      infarction results in clinical benefit through early plaque stabilization.
      METHODS AND RESULTS: The study population consisted of 77 patients who underwent
      coronary balloon angioplasty of the infarct-related artery during the first month
      of acute myocardial infarction. These patients belonged to the cohort of the
      Pravastatin Turkish Trial (PTT). Forty of them were assigned randomly to have
      immediate pravastatin (40 mg/day) therapy adjunctive to thrombolytic therapy
      regardless of serum lipid levels and received statin treatment throughout the
      study. Lipid levels were determined immediately after admission and before
      angioplasty and at the end of 6 months. Patients were re-evaluated clinically and
      angiographically for cardiovascular adverse events and restenosis after a 6-month
      follow-up period. The baseline angiographic and clinical characteristics of the
      two groups were similar. The incidence of angina was significantly lower in the
      pravastatin group (30.0%, 12 patients) compared to the control group (59.5%, 22
      patients) (p = 0.018). The cumulative major adverse cardiac events in the
      pravastatin group were significantly lower when compared to the control group
      (32.5% vs. 75.6%, p = 0.0001). CONCLUSIONS: Early initiation of pravastatin
      therapy immediately after an acute myocardial infarction significantly decreased
      the frequency of major cardiac adverse events. Such early potential clinical
      benefits further strengthen the rationale for starting statin treatment as soon
      as possible after acute coronary events particularly in patients in whom invasive
      intervention is planned.

PMID- 12222699
TI  - "Thrombus in transit"--the role of echocardiography in the diagnosis of massive
      pulmonary embolism and a review of the literature.
AB  - The diagnosis of acute pulmonary embolus is often difficult. We present a case
      history where bedside transthoracic echocardiography provided a rapid and
      convenient aid to diagnosis by demonstrating a venous "thrombosis in transit" as
      a spiral shaped mass in the right atrium prolapsing into the right ventricle. We
      also review the management and outcome in recent, similar cases. Overall
      mortality is 33% for pulmonary embolus and associated thrombus in transit.
      Transthoracic echocardiography may be a useful tool in the diagnosis of pulmonary
      embolus. The presence of thrombus in the right heart is a rare finding. The
      outcome in these patients is determined by the clinical presentation rather than
      by the identification of thrombus.

PMID- 12222701
TI  - Primary lymphoma of the heart: three-dimensional reconstruction.
AB  - Primary cardiac lymphoma is defined as a lymphoma of the heart and pericardium
      with little or no extracardiac or local involvement such as mediastinal lymph
      nodes or pleural effusion. Most cases are diagnosed only post mortem (1). If this
      disease could be diagnosed earlier, therapy with chlorpropamide, doxorubicin,
      vincristine and prednisone (CHOP) could bring about a remission (2,3,4).
      Transoesophageal echocardiography with three-dimensional acquisition is a new
      technique which can allow earlier diagnosis, and facilitate guided transvenous
      biopsy (5,6). We here report an example of the pre-mortem diagnosis of cardiac
      lymphoma by these techniques.

PMID- 12222702
TI  - Covered stent graft for primary PTCA of an aortocoronary vein graft.
AB  - Covered stent graft by entrapping the thrombus between the vessel wall and stent
      might be helpful in preventing distal embolization and "no reflow" in a high-risk
      patient cohort. We here present a case with successful restoration of coronary
      flow in a highly thrombogenic milieu (acute myocardial infarction) with
      implantation of two covered stent grafts which by entrapping the thrombus avoided
      the distal embolization and "no reflow" in a totally occluded saphenous vein
      graft (SVG). However, stent length should be longer than the measured lesion
      length since choosing the exact diameter will not cover the plaque elongification
      secondary to the dilation process which is specifically significant in SVGs
      because of the softness of the plaque.

PMID- 12222703
TI  - Superior vena cava syndrome and infection of pacing leads in one patient.
AB  - The superior vena cava (SVC) syndrome is an uncommon complication due to
      permanent transvenous pacemaker electrodes. Infection of the leads is a risk
      factor for its occurrence. After being treated for SVC syndrome, due to multiple
      pacemaker leads, with thrombolysis and coumarine therapy, our patient was
      diagnosed with repetitive positive blood cultures. Because of relapsing SVC
      syndrome all pacemaker material was surgically removed. Recovery was complete and
      the patient remained pacemaker-independent. Culture of the leads showed the same
      coagulase-negative staphylococci as in the blood cultures. The indications for
      pacemaker implantation should always be rigorously defined and complications
      thoroughly investigated and treated.

PMID- 12222704
TI  - Prevention of mother-to-child transmission of HIV: reflections on implementation
      of PMTCT in the developing world.

PMID- 12222705
TI  - Treatment of sleep problems in small children.

PMID- 12222706
TI  - Excessive fluid intake before and during delivery causing water intoxication in
      the mother and her offspring.

PMID- 12222707
TI  - Sidestream end-tidal capnometry as related to infant's position and maturation.
AB  - The objective of this study was to investigate the effect of body position on
      sidestream, end-tidal carbon dioxide (EtCO2) wave measurements in maturing
      infants. Sidestream EtCO2 wave patterns were analysed longitudinally in 20
      preterm infants (born at > or = 32 wk) at 32-37 wk gestation, and in 39 full-term
      controls. Capnography measurements included maximal EtCO2, inspired CO2 and
      frequency of apnoea events (>3 s) in the supine, supine with inclination, side
      and prone positions. Apnoea frequency decreased during maturation, and was less
      prevalent in the prone than in the supine and side positions in preterm as well
      as in term infants (p < 0.05). No clinically significant apnoea episodes were
      found in our cohort. EtCO2 in term infants was lower than that in preterm infants
      (p < 0.05) and was not affected by sleep position in the most premature (<33 wk)
      and in term infants (>36 wk). EtCO2 was higher in the prone position than in
      supine or side positions in infants between 33 and 35 wk gestation (p < 0.01).
      CONCLUSION: Short apnoeic episodes decrease during maturation, and are less
      prevalent in the prone position in maturing infants (32-37 wk). Only modest
      changes in EtCO2 were recorded in the different positions during maturation.

PMID- 12222709
TI  - Decline of maternal hepatitis A virus antibody levels in infants.
AB  - Hepatitis A is a common viral infection causing substantial morbidity and
      mortality. The anti-hepatitis A virus (HAV) vaccination in infants would
      guarantee control of the infection. However, the immunogenicity of the HAV
      vaccine in infants could be impaired by the presence of passively acquired
      maternal HAV antibodies. This study evaluated the prevalence of HAV antibodies in
      103 women at delivery and in their babies in the first year of life. Eighteen
      mothers (17.5%) had anti-HAV serum level >10 mIU ml(-1). In their infants the
      anti-HAV level was still positive in 11 out of 18 (61.1%) at 12 mo. Two out of 85
      infants born to anti-HAV-negative mothers and anti-HAV negative at birth were
      found to be positive at 5 mo of age. CONCLUSION: It is proposed that all women be
      screened at delivery for anti-HAV antibodies. Children born to anti-HAV-negative
      mothers could be vaccinated early during the first year of life, whereas
      vaccination could be postponed in children born to anti-HAV-positive mothers, if
      necessary.

PMID- 12222708
TI  - Effect of different types of feeding on fatty acid composition of erythrocyte
      membrane lipids in full-term infants.
AB  - Significantly higher levels of arachidonic acid (AA) and docosahexaenoic acid
      (DHA) in plasma lipids have previously been reported in 2 to 8-wk-old as well as
      in 6 to 12-mo-old full-term infants fed exclusively human milk than in infants
      exclusively receiving formula without AA and DHA. However, in real life many
      infants receive both human milk and breast milk substitute formula. Healthy, full
      term infants aged 2 to 12 mo and fed exclusively human milk (n = 29, age: 29.2
      [14.6] wk, mean [SD], no human milk substitute formula), exclusively formula
      without AA and DHA (n = 30, age: 26.6 [15.2] wk, no human milk after the age of 1
      mo) or combined diet (n = 38, age: 30.3 [12.8] wk, human milk for > 1 mo and
      breast milk substitute formula) were investigated in this cross-sectional study.
      Fatty acid composition of erythrocyte membrane phosphatidylethanolamine (PE),
      phosphatidylcholine and sphingomyeline lipids was determined by high-resolution
      capillary gas-liquid chromatography. The most pronounced diet-related differences
      were seen in PE lipids. Values of PE alpha-linolenic acid (0.07 [0.05] vs 0.26
      [0.18] vs 0.19 [0.19], median [range from the 1st to the 3rd quartile],
      exclusively breastfed vs. exclusively formula fed vs combined diet),
      eicosapentaenoic acid (0.19 [0.13] vs 0.35 [0.23] vs 0.27 [0.31]) and dihomo
      gamma-linolenic acid (1.34 [0.42] vs 1.86 [0.62] vs 1.58 [0.73]) were
      significantly lower in exclusively breastfed infants than in those fed formula,
      exclusively or partially. In contrast, PE AA (26.48 [2.50] vs 24.34 [4.74] vs
      24.94 [3.64]) and DHA (4.93 [2.91] vs 3.51 [2.14] vs 3.58 [2.27]) values were
      significantly higher in exclusively breastfed infants than in the other two
      groups. CONCLUSION: In full-term infants aged 2 to 12 mo, erythrocyte membrane AA
      and DHA values are significantly higher with exclusive breastfeeding than with
      partial breastfeeding or exclusive feeding of formula without AA and DHA.

PMID- 12222710
TI  - Anogenital bacteriology in non-abused preschool children: a descriptive study of
      the aerobic genital flora and the isolation of anogenital Gardnerella vaginalis.
AB  - The purpose of the study is to describe the genital aerobic bacterial flora
      including Gardnerella vaginalis in girls and the occurrence of anal G. vaginalis
      in both genders. From a group of 3773 children, 278 (99 boys and 179 girls) with
      a mean age of 5.63 y (range: 5.13-6.73) were recruited. Inclusion in the study
      was based on self-selection, whereby parents who did not suspect any occurrence
      of sexual abuse of their child gave informed consent to participate. Several
      mechanisms were undertaken to exclude abused children. At least one bacterial
      species was isolated from the genitals of 59 (33.9%) girls. Most isolates (39 out
      of 99) were bacteria representing skin flora (staphylococci and coryneform
      organisms), with viridans streptococci and related organisms as the second most
      common group of isolates (31 out of 99). S. anginosus was the single most
      frequent bacterial species identified (17 isolates). Streptococcus pyogenes was
      isolated from the genitals of two girls, Streptococcus pneumoniae from one girl
      and Haemophilus influenzae from eight girls. G. vaginalis was not isolated from
      the genitals in any girl, but the organism was isolated from the anal canal in
      three children.

PMID- 12222711
TI  - Non-classical 21-hydroxylase deficiency in children: association of
      adrenocorticotropic hormone-stimulated 17-hydroxyprogesterone with the risk of
      compound heterozygosity with severe mutations.
AB  - AIM: To investigate the association between levels of 17-hydroxyprogesterone (17
      OHP) and the risk of being compound heterozygous for severe mutations in children
      with non-classical 21-hydroxylase deficiency (NC21OHD). METHODS: In 86 Spanish
      NC21OHD children (75 families) an analysis of the 21-hydroxylase (21-OH) gene was
      performed by CYP21B-specific polymerase chain reaction amplification, allele
      specific oligonucleotide hybridization and Southern blotting. Familial analysis
      established how the alleles segregated, and allowed the selection of 21-OH
      genotyped normal and carrier children, which proved useful in determining a more
      precise definition of the cut-off for diagnosis. Receiver operating
      characteristics (ROC) curve analyses were performed to determine the potential
      value of 17-OHP in predicting compound heterozygosity for severe mutations.
      RESULTS: Thirty-four of the 86 children (39%) were found to carry one severe 21
      OH mutation (7.3% deletions or conversions, 2.7% 655G, 2.7% Q318X, 1.3% 1172N,
      1.3% R356W, and 3.3% double microconversions or small conversions involving
      single exons). The predominant mutation was V281L (56.7%). P453S and P30L were
      less frequent (3.3 and 2%). No patient showed two severe mutations. The degree of
      enzymic deficiency, as measured by basal or adrenocorticotropic hormone (ACTH)
      stimulated 17-OHP levels in fully genotyped patients, but not clinical severity
      (age and number of symptoms at diagnosis), was found to be significantly greater
      in children with the severe/mild genotype. ROC curve analyses revealed a strong
      association between ACTH-17-OHP and genotype (area under the curve 0.908, SE
      0.057). CONCLUSION: ACTH-stimulated 17-OHP may predict the risk of severe
      mutations in compound heterozygosity in children (maximum predictive value 93%
      sensitivity and 83% specificity for a cut-off at 151 nmol l(-1)), although a
      certain overlap in individual values is observed and performance of molecular
      analysis should never be obviated in the genetic counselling of these patients.

PMID- 12222712
TI  - New approach to osteopenia in phenylketonuric patients.
AB  - AIM: To study bone mineralization in a group of phenylketonuric patients and to
      search for a possible relationship between bone mineral density, dietary control,
      serum minerals and nutrition intake. The response to treatment with low-dose 1.25
      (OH)2 vitamin D in patients with osteopenia was evaluated. METHODS: Twenty-eight
      phenylketonuric patients (age range: 10-33 y) on dietary treatment were
      investigated. Bone density at the lumbar spine (Dual Energy X-ray
      Absorptiometry), bone formation markers (osteocalcin and bone alkaline
      phosphatase), serum minerals, index of dietary control and protein, vitamin D and
      mineral intakes were determined. RESULTS: Of the patients studied, 78.6% had good
      dietary compliance (462 +/- 89 micromol/L). Mean protein, vitamin D and mineral
      intakes met the recommended dietary allowances (RDAs). Nevertheless, 8 patients
      had calcium intakes lower than 1000 g/d, and a positive correlation between Z
      score and calcium (r = 0.585; p = 0.002) or phosphorus intake (r = 0.546; p =
      0.005) was observed. Osteopenia was detected in 14 patients (50%). Moreover, bone
      alkaline phosphatase in phenylketonuric patients older than 18 y of age was
      significantly lower than that in controls (p < 0.0001). No correlation was found
      between bone mineral density, age, serum minerals, bone formation markers or
      index of dietary control. Treatment with 0.25 microg/d calcitriol significantly
      increased bone density in 6 patients. CONCLUSION: A defect in bone mineralization
      was detected in 50% of patients in our series. The correct amount of formula
      intake seems to be necessary for bone mineralization in phenylketonuric patients.
      Calcitriol can be a useful treatment for these patients, although more studies
      are needed to confirm these results. Hypercalcaemia and hypercalciuria need to be
      carefully monitored.

PMID- 12222713
TI  - Homocysteine and other vascular risk factors in patients with phenylketonuria on
      a diet.
AB  - The aim of this study was to investigate the known risk factors, such as lipids,
      homocysteine and endothelin, for the development of coronary artery disease (CAD)
      in phenylketonuria (PKU) patients, depending on their diet. The PKU patients (n =
      74) were divided into two groups. Group A (n = 34; mean age 6.78 +/- 1.5 y)
      adhered strictly to a diet and group B (n = 40; mean age 8.0 +/- 3.2 y) did not
      comply with the diet. The control group comprised 50 healthy non-PKU children.
      All groups were evaluated for blood levels of homocysteine and vitamin B6 by high
      performance liquid chromatography, vitamin B12 and folate in serum by a
      radioassay, lipids by a routine method, and lipoprotein(a) and endothelin-1 with
      an immunoassay. Homocysteine levels (28.65 +/- 3.3 micromol l(-1)) were increased
      in group A compared with group B (6.86 +/- 1.6 micromol l(-1)) and the controls
      (6.9 +/- 2.0 micromol l(-1)) (p < 0.001). Vitamin B6 (10.7 +/- 10.9 nmol l(-1)),
      vitamin B12 (98.5 +/- 22.3 pmol l(-1)), folate (2.35 +/- 1.3 nmol l(-1)) and
      lipids were decreased in group A. The other vascular risk factors, which were not
      dependent on diet [lipoprotein(a) and endothelin-1], did not differ among the
      three groups. CONCLUSION: PKU patients on a strict diet had low vitamin B6,
      vitamin B12 and folate levels resulting in moderate hyperhomocysteinaemia. The
      evaluation of these vitamins at short intervals and their supplementation could
      be an early measure in the prevention of CAD.

PMID- 12222714
TI  - Inhibitors in the Swedish population with severe haemophilia A and B: a 20-year
      survey.
AB  - AIM: To survey the entire population (n = 116) afflicted with severe haemophilia
      A or B born in Sweden over a 20-y period (1980-1999), and to examine the
      epidemiological, genetic and clinical aspects of development of inhibitors to
      factors VIII and IX (FVIII/FIX). METHODS: One hundred of the subjects had
      haemophilia A and 16 had haemophilia B. All of these subjects had received
      prophylactic treatment and had a check-up of inhibitor status at least twice a
      year. Sixty-one were born between 1980 and 1989 and 55 between 1990 and 1999.
      RESULTS: Nineteen percent (19/100) of those with haemophilia A and 37% (6/16)
      with haemophilia B developed inhibitors at 12-18 mo of age, after exposure to
      FVIII/FIX concentrates for an average of 14 d in the case of haemophilia A and 16
      d in haemophilia B. All patients with inhibitors carried mutations that impaired
      protein synthesis. The high incidence of FIX inhibitors may have been due to the
      large number of complete deletions (13%) in the Swedish haemophilia B population.
      Patients with haemophilia A showed no significant increase (p = 0.65) in
      incidence of inhibitors (n = 10/48, total incidence 21%) in the 1990s, when they
      were treated mainly with recombinant products, as compared to the 1980s (n =
      9/52, 17%), when they received intermediate/high-purity plasma-derived
      concentrates. CONCLUSION: Our population-based study verifies that genotype has a
      general impact on the incidence of FVIII/FIX inhibitors, and that recombinant
      FIII/FIX concentrates are not a predisposing factor for inhibitor development.

PMID- 12222715
TI  - Neutrophil regeneration precedes healing of tissue destruction, as indicated by
      serum C-reactive protein, in children with cancer recovering from neutropenic
      fever.
AB  - AIM: To evaluate the relationship between absolute neutrophil count and C
      reactive protein (CRP) in the recovery phase of neutropenic fever among
      paediatric patients with cancer. METHODS: A total of 102 paediatric oncology
      patients with 177 episodes of fever and neutropenia was studied prospectively in
      a two-centre setting. Antimicrobial therapy was discontinued 9 d (mean) post
      initiation with a mean absolute neutrophil count of 1.8 x 10(9) l(-1) and CRP of
      32 mg l(-1). RESULTS: The mean level of CRP below 20 mg l(-1) was reached on day
      12. The level of CRP peaked on the day following the commencement of
      antimicrobial therapy. Throughout the episodes of fever and neutropenia higher
      levels of CRP were associated with a lower absolute neutrophil count. Following
      defervescence the pace of marrow recovery as evidenced by an increasing absolute
      neutrophil count to > 0.2 and > 0.5 x 10(9) l(-1) was more rapid than the
      normalization of serum CRP. There was a 2-3 d lag period between absolute
      neutrophil count exceeding the level of 200 x 10(6) l(-1) and the return of CRP
      to a baseline level. All episodes were treated successfully and there were no
      fatalities. CONCLUSION: Among patients recovering from neutropenia and fever the
      signs of marrow recovery remain the key criterion in evaluating the safety of
      discontinuing antimicrobial therapy, with serum CRP remaining more of an
      indicator of ongoing tissue repair.

PMID- 12222716
TI  - Oral versus rectal midazolam as a pre-anaesthetic sedative in children receiving
      dental treatment under general anaesthesia.
AB  - Dental treatment in children who are too young or too apprehensive to cooperate
      is often performed under sedation. In Sweden, the tradition has been to
      administer sedatives rectally in small children, but oral liquid sedation is now
      increasingly used. AIM: To compare the sedative effects of oral and rectal
      administration of midazolam in children undergoing dental treatment under general
      anaesthesia and to assess acceptance of sedative administration, acceptance of
      application of the facemask, and amnesia. METHODS: Fifty children aged 2-7 y were
      randomly allocated to receive either liquid oral or rectal sedation, with 25
      children in each group. RESULTS: The sedative effect of rectal administration was
      higher, but not statistically significantly, than that of oral administration (p
      = 0.07). No significant differences in acceptance of sedative administration,
      acceptance of mask application or amnesia were found between the groups.
      CONCLUSION: Both the oral and the rectal routes can in most cases be appropriate.
      However, the better sedative effect of rectal administration of midazolam makes
      it a more favourable route in pre-cooperative and non-compliant children.

PMID- 12222717
TI  - Neonatal hip instability: results and experiences from ten years of screening
      with the anterior-dynamic ultrasound method.
AB  - AIM: To record the results and experiences from a 10-y screening period with the
      anterior-dynamic ultrasound method for detecting neonatal hip instability.
      METHODS: An ultrasonographic improvement of the Palmen/Barlow test was used. The
      screening programme included 22,047 newborns. Decisions about treatment were made
      solely on the ultrasound result. RESULTS: It was found that 175 infants
      (7.9/1000) had at least one unstable hip--dislocated or dislocatable. Dislocated
      hips were found in 1.1/1000. Dislocatable hips were found in 6.8/1000 but only
      1.1/1000 needed treatment. The total frequency of treatment was 2.2/1000. All
      cases but one were diagnosed before discharge from the maternity ward. The rate
      of surgery was 0.1/1000 newborns. Girls were more affected than boys, by a ratio
      of 3:1. Among the affected hips 64.4% were a left hip. CONCLUSION: Neonatal hip
      instability is always present at birth and can be diagnosed immediately after
      birth. We have no indications that instability can appear at a later stage. The
      anterior-dynamic ultrasound screening programme is an efficient tool to diagnose
      neonatal hip instability and to decide when to begin treatment.

PMID- 12222718
TI  - Neurobehavioral and developmental profile of very low birthweight preterm infants
      in early infancy.
AB  - AIM: To describe the neurobehavioral and developmental profile of very low
      birthweight (VLBW) preterm infants in early infancy. METHODS: Twenty VLBW infants
      and 10 term control infants were assessed at term, 3 and 6 mo of age.
      Neurobehavioral assessments included the Neonatal Behavioral Assessment Scale
      (NBAS) at term; the Infant Behavioral Assessment at term, 3 and 6 mo of age and
      the Behavioral Rating Scale of the Bayley Scales of Infant Development-II (BSID
      II) at 3 and 6 mo of age. Development was evaluated with the Bayley Motor and
      Mental Scale at 3 and 6 mo. RESULTS: At term age VLBW infants differed from term
      infants on all the clusters and supplementary items of the NBAS. VLBW infants
      also showed more stress and less approach behavior at term and 6 mo of age and
      more problems with self-regulation in all subsystems at 6 mo of age. Moreover,
      VLBW infants performed lower on the Bayley Motor, Mental and Behavioral Rating
      Scale: 12 VLBW infants scored questionable or non-optimal on the Psychomotor
      Development Index and 18 questionable or non-optimal on the Behavioral Rating
      Scale. These results support the need for neurobehavioral intervention of VLBW
      infants in the first 6 mo of life. CONCLUSION: Almost all VLBW infants showed non
      optimal motor quality behavior at 6 mo and encountered far more problems with
      self-regulation compared with term infants.

PMID- 12222719
TI  - Low birthweight children: coping in school?
AB  - AIM: To describe and compare school performance and IQ at 11 y of age in a
      population of 130 children weighing less than 2000 g at birth without any major
      handicaps (low birthweight) and a random control sample of 131 children born at
      term weighing over 3000 g (normal birthweight); and to evaluate the relative
      strength of parental factors versus child birthweight in predicting IQ. METHODS:
      The mothers and teachers completed validated questionnaires addressing school
      performance and the child's IQ was evaluated by WISC-R, prorated. In addition,
      socioeconomic status was investigated using different questionnaires. RESULTS:
      According to maternal reports, twice as many low birthweight children had school
      problems and three times as many of these children were referred to the School
      Psychological Service. Mean prorated IQ was 5 points lower in the low birthweight
      group. No statistically significant difference was found for mean IQ between the
      groups with birthweights of less than 1500 g vs 1500-2000 g. In a multivariate
      linear regression analysis, parental factors accounted for 13% of the variance in
      child IQ compared with only 3% accounted for by child birthweight. CONCLUSION:
      Low birthweight significantly increases the risk of school problems.

PMID- 12222720
TI  - Cerebral palsy in preterm infants: a population-based case-control study of
      antenatal and intrapartal risk factors.
AB  - Previous studies have indicated that foetomaternal infection increases the risk
      of spastic cerebral palsy (CP) in term infants, whereas this association appears
      to be less evident in preterm infants. The aim of this study was to analyse
      infection-related risk factors for spastic CP in preterm infants. A population
      based series of preterm infants with spastic CP, 91 very preterm (<32 wk) and 57
      moderately preterm (32-36 wk), born in 1983-90, were included and matched with a
      control group (n = 296). In total, 154 maternal, antenatal and intrapartal
      variables were retrieved from obstetric records. In the entire group,
      histological chorioamnionitis/pyelonephritis, long interval between rupture of
      membranes and birth, admission-delivery interval <4 h and Apgar scores of <7 at 1
      min just significantly increased the risk of CP, and Apgar scores of <7 at 5 and
      10 min were strongly associated with an increased risk. Abruptio placentae, Apgar
      scores <7 at 1 min and pathological non-stress test (reason for delivery) were
      significant risk factors of CP only in the moderately preterm and hemiplegic
      groups, whereas fever before delivery was a significant risk factor in the very
      preterm and spastic diplegic groups. Antibiotics during pregnancy was associated
      with CP only in the spastic diplegic CP group. CONCLUSION: Antenatal infections
      marginally increased the risk of CP. Low Apgar score and abruptio placentae were
      associated with CP, especially in moderately preterm infants with hemiplegic CP.

PMID- 12222721
TI  - Treatment of sleep problems in families with small children: is written
      information enough?
AB  - The aim of this study was to evaluate a standardized sleep programme, i.e. a two
      step variation of graduated extinction, where the child is first taught to fall
      asleep by him/herself at bedtime (first intervention) and 2 wk later also after
      night wakings (second intervention). The outcome after consultations with a
      therapist followed by telephone support during both interventions was compared
      with the outcome after giving written information only during the first
      intervention and therapist support during the second. A total of 67 families with
      infants exhibiting spontaneous awakening and crying episodes during the night
      were randomly assigned to either programme. There were no significant differences
      in terms of outcome between the two groups. In both groups the number of
      registered night wakings decreased immediately following the first intervention.
      At registration, at 1 mo and 3 mo later, all parents, with the exception of one
      couple at the 3-mo follow-up, reported that the sleep problem had improved.
      CONCLUSION: If parents experience their infant's night awakenings as a problem,
      teaching their infant to fall asleep by him/herself usually solves this problem
      quickly. Written information is in most cases sufficient to help parents
      introduce the new evening routines.

PMID- 12222722
TI  - Effect of dry bed training on behavioural problems in enuretic children.
AB  - Children with nocturnal enuresis (n = 91) selected by school doctors in The
      Netherlands from 1991 to 1994 were included in a study to assess the course of
      behavioural problems especially when the children became dry after the Dry Bed
      Training (DBT) programme. The Child Behaviour Checklist (CBCL) questionnaire was
      completed by 88 parents (96%) prior to DBT (T1) and by 83 parents (91%) 6 mo
      after DBT (T2). The mean CBCL total problem score at T1: 24.0 (range 2-91, SD 16)
      was significantly higher than that of a Dutch norm group: 20.45, (p=0.025).
      Compared to T1, the mean CBCL total problem score at T2 was 16.8 (range 0-73; SD
      14.7; p < 0.0001). Of the children with CBCL total problem scores at T1 in the
      borderline or clinical range, 92% became dry and 58% improved to the normal
      range. At T2, the children seemed to have less internal distress, fewer problems
      with other people, and were less anxious and/or depressed. CONCLUSION: Children
      with behavioural/emotional problems who wet their beds need not first be treated
      for their behavioural/emotional problems. Bedwetting can be treated successfully
      with DBT when other treatments such as normal alarm treatment have failed, and
      alarm treatment/DBT can have a positive influence on behavioural/emotional
      problems.

PMID- 12222723
TI  - Abortion requests among adolescents in comparison with young adults in a Swiss
      region (1990-1998).
AB  - AIM: To examine the recent evolution of abortion request rates among adolescents
      and young adults in the Canton of Vaud (Switzerland) and to describe the
      circumstances of the abortion requests and sociodemographic characteristics by
      age subgroups and nationality. METHOD: Data for women aged 14 to 24 y living in
      Vaud were selected from the 12,358 abortion requests from residents aged 14-49 y
      between 1990 and 1998. RESULTS: Overall, abortion request rates by age were
      stable over the study period. However, rates for non-Swiss women were two to
      three times higher than those for Swiss women, at 4.5 [95% confidence interval
      [CI]: 3.8-5.2] vs 2.4 [95% CI: 2.1-2.7] per 1000 adolescents below the age of 18,
      18.1 [95% CI: 17.2-18.9] vs 8.0 [95% CI: 7.1-8.8] per 1000 women aged 18-19 and
      30.5 [95% CI: 29.1-32.0] vs 10.2 [95% CI: 9.6-10.8] per 1000 women aged 20-24.
      The ratio of abortions to live births was greatest for women under 20 y of age.
      at 1.9, in comparison with the ratio observed among adult women aged 20-24 (at
      0.4). The abortion rate per 1000 conceptions >6 wk remained stable; this rate was
      590 per 1000 among 14-19-y-olds in 1997. CONCLUSION: The abortion request rate
      among youths in this Swiss region has not increased between 1990 and 1998.
      Efforts must be intensified to ensure universal access to family planning
      services and contraception, especially for young foreign women and adolescents.

PMID- 12222724
TI  - Acute abdominal attack of hereditary angioneurotic oedema associated with
      ultrasound abnormalities suggestive of acute hepatitis.
AB  - Hereditary angioneurotic oedema (HANO) is an autosomal dominant disorder caused
      by a deficiency of the inhibitor protein Cl-esterase. Recurrent subcutaneous
      and/or submucosal oedema formation is a hallmark of this disease. HANO is a rare,
      but potentially life-threatening disorder with a mortality around 20-30%. Acute
      oedematous abdominal attacks of HANO can mimic a surgical emergency; this is
      exemplified by the case of a 14-y-old male patient with HANO admitted for such
      clinical manifestations. CONCLUSION: Diagnostic clues include ascites and
      abnormalities of hepatic structure visible with ultrasound during the oedematous
      attack. The importance of appropriate treatment is emphasized.

PMID- 12222725
TI  - Findings in familial haemophagocytic lymphohistiocytosis prior to symptomatic
      presentation.
AB  - Familial haemophagocytic lymphohistiocytosis (FHL) is a rare, autosomal recessive
      disease of infancy and early childhood clinically characterized by fever,
      hepatosplenomegaly, lymphadenopathy, rash, neurological symptoms and icterus.
      Common laboratory findings include cytopenia, elevated liver enzymes,
      hyperbiliriubinaemia, hypofibrinogenaemia and hypertriglyceridaemia. The natural
      killer cell function is frequently decreased or absent. A diffuse
      lymphohistiocytic infiltration is seen in the reticuloendothelial system, often
      with haemophagocytosis. Molecular diagnosis is available in a minority of FHL
      families. Without adequate treatment and bone-marrow transplantation, the disease
      is fatal. A 6-wk-old child with FHL is presented. Shortly before the clinical
      onset of the disease, blood testing and bone-marrow examination had been carried
      out. All results were considered normal at that time. CONCLUSION: Blood tests and
      bone-marrow examination may be normal shortly before the clinical presentation
      and therefore do not exclude the diagnosis of FHL. There is a need for extended
      molecular diagnostic possibilities.

PMID- 12222726
TI  - Amplitude-integrated encephalography in pyridoxine-dependent seizures and
      pyridoxine-responsive seizures.
AB  - Pyridoxine-dependent seizures are rare in newborn infants, although recent data
      suggest that the prevalence probably is underestimated. In all newborn infants
      with recurrent epileptic seizures the general recommendation is to administer
      pyridoxine and simultaneously record an electroencephalogram (EEG). CONCLUSION:
      One infant with pyridoxine-responsive seizures and another with pyridoxine
      dependent seizures had different electroclinical responses on amplitude
      integrated EEG monitoring (aEEG) when pyridoxine was administered.

PMID- 12222727
TI  - Idiopathic intracranial hypertension presenting as hemiplegic migraine.
AB  - A 14-y-old girl presented with a 2 h history of left hemiplegia preceded by mild
      left-sided sensory disturbance. She had experienced migraines for several years
      and there was a strong family history of migraine, including hemiplegic migraine
      in one of her sisters. Her hemiplegia and headache responded to sumatriptan but
      her headache and vomiting subsequently returned. She was found to have
      intracranial hypertension and developed papilloedema and paracentral scotomas.
      Further history revealed she had been taking minocycline for acne. CONCLUSION: An
      association between hemiplegic migraine and pseudotumour cerebri has not
      previously been reported. There may be a case for examining patients with
      pseudotumour cerebri for the calcium channel mutation (CACNA1A).

PMID- 12222728
TI  - Massive foetomaternal haemorrhage associated with a favourable outcome after two
      years.

PMID- 12222729
TI  - N-acetylcysteine overdosage after insignificant acetaminophen intake.

PMID- 12222730
TI  - Cognitive brain potentials to novel acoustic stimuli in adult dyslexic readers.
AB  - Event-related brain potentials were recorded in two three-stimulus oddball tasks
      in 13 adult dyslexic and 13 age- and IQ-matched normal readers. The stimuli
      consisted of a random series of frequent (80%) and non-frequent tones (10%) as
      well as occasionally inserted novel sounds (10%). The experiment comprised an
      active (response to the rare target tone) and a passive listening condition. No
      performance differences were found for dyslexic and normal readers in the active
      task. In both conditions, novel sounds evoked a centrally distributed P3a
      component followed by a P3b-component most prominent at parietal electrodes for
      target and novel sounds. Additionally, a slow negativity emerged after
      presentation of novel sounds at frontal electrodes. In the active condition only,
      peak amplitude of the P3a and the frontal slow negativity to novel stimuli were
      slightly enlarged for dyslexic readers. These findings indicate a larger
      distractability of dyslexic readers (enhancement of P3a to novel tones).
      Furthermore, we propose that dyslexics need to employ more cognitive resources to
      refocus on the task at hand (as indicated by the enlarged slow frontal
      negativity).

PMID- 12222731
TI  - Dyslexia: nature and nurture.
AB  - This paper explores the balance of genetic and environmental influences on
      dyslexia in generally supportive educational environments. Evidence from family
      studies suggests and research with identical and fraternal twins confirms the
      presence of strong genetic influences on dyslexia, though the way dyslexia is
      defined influences the degree of genetic influence. The behavioural genetic
      evidence is supported with molecular genetic evidence from DNA analyses
      suggesting regions on several different chromosomes where genes related to
      dyslexia are likely to be found. The behavioural and molecular genetic analyses
      are also applied to different component word reading skills (orthographic coding
      and phonological decoding) as well as to related language skills (phoneme
      awareness) to better understand the genetic and cognitive pathways to dyslexia.

PMID- 12222732
TI  - Surface and phonological subtypes of adult developmental dyslexia.
AB  - In order to assess the efficacy of phonological versus surface dyslexia subtyping
      within an adult dyslexic population, 45 adult dyslexics were assessed on the
      Castles and Coltheart (1993) irregular word and non-word reading tasks. Based on
      the performance of a matched group of 28 non-dyslexics, between 62 and 75% of the
      dyslexics were divided into phonological and surface subtypes. Phonological
      dyslexics were those individuals who presented evidence of relatively poor or
      inefficient non-word reading, whereas the surface dyslexics were those who
      indicated relative difficulties with irregular word reading. The proportions of
      dyslexics within each subtype varied according to the use of accuracy-based or
      latency-based procedures, but were consistent with previous findings with
      children. Subsequent comparisons between the groups on measures of phonological
      processing, lexical access and word knowledge/recognition indicated few
      differences between the two subtypes and, in particular, no differences on
      measures of phonological ability. The lack of observed differences on such
      measures casts doubt on the efficacy of this procedure for explaining individual
      differences amongst adult dyslexics and as a practical procedure for diagnosis
      and intervention.

PMID- 12222733
TI  - The dyslexia ecosystem: commentary 1.

PMID- 12222734
TI  - The dyslexia ecosystem: commentary 2.

PMID- 12222735
TI  - The dyslexia ecosystem: commentary 3.

PMID- 12222736
TI  - Response to letters to the editor by Felicity Patterson, Dyslexia 7:174-177.

PMID- 12222737
TI  - A review of epidemiologic studies on aluminum and silica in relation to
      Alzheimer's disease and associated disorders.
AB  - Although the neurotoxicity of aluminum is well established, the association
      between the metal and dementia or associated disorders remains a subject of
      debate. In this article, we present a review of articles published on
      epidemiologic studies of this subject. Different sources of exposure are
      considered (occupational exposure, aluminum-containing products), with emphasis
      on drinking water. We separate the various health effects of aluminum into three
      categories: neurological disorders (other than cognitive decline or AD);
      cognitive decline; and dementia or Alzheimer's disease. Furthermore, we present
      the results obtained on silicon in drinking water, a chemical constituent that
      interacts with aluminum. We conclude that not enough epidemiological evidence
      supports a link between aluminum in drinking water and AD. The role of silica in
      drinking water has been less studied, and clear results have not yet emerged.

PMID- 12222738
TI  - Polychlorinated biphenyls in the blood plasma: current exposure of the population
      in Germany.
AB  - Until the 1970s, polychlorinated biphenyls (PCB) were used as industrial
      chemicals for diverse commercial applications, leading to a ubiquitous
      contamination of nature and man. In the 1980s, PCBs were prohibited by law in
      many industrialized countries. Hence, in recent years a steady decline in PCB
      levels has been seen. Here we report on PCB plasma levels in children and adults
      in Germany in 1998. PARTICIPANTS AND METHODS: 130 children/youth (0 to <18 y) and
      494 adults (18 to 65 y) living in an urban environment participated in this
      study. Occupational exposure to PCBs was excluded by questionnaire. Gas
      chromatography/electron capture detection was used to analyze blood plasma
      samples. RESULTS: In all blood specimens, PCB congeners 28, 52, and 101 were
      below the limit of quantification (<0.1 microg/L) and only the congeners 138,
      153, and 180 were detected. The 95th percentiles in the age groups 0 to <6 y, 6
      to <12 y, 12 to <18 y, 18 to 25 y, 26 to 35 y, 36 to 45 y, 46 to 55 y, and >55 y
      were as follows: PCB 138: 1.02; 1.05; 0.61; 1.01; 1.22; 1.44; 2.23; 2.94 microg/L
      plasma; PCB 153: 1.47; 1.23; 0.59; 1.26; 1.53; 2.11; 3.27; 3.98 microg/l plasma;
      PCB 180: 0.88; 1.23; 0.39; 0.88; 1.16; 1.71; 2.16; 3.31 microg/L. DISCUSSION: In
      adults, plasma levels of PCBs increased with age. In comparison with published
      reference values on internal PCB exposure in the population in Germany, based on
      data obtained in 1991/4 and 1994/5, the steady decline in PCB levels reflects the
      falling external and internal PCB exposure after the ban on PCB. For the first
      time, current PCB exposure during childhood and adolescence in Germany is
      provided here. In childhood, internal PCB exposure declined with age, especially
      in children who had been breastfed. An impact of breastfeeding on internal PCB
      exposure was found in age groups up to 12 years old.

PMID- 12222739
TI  - Human health risks of dioxins for populations living near modern municipal solid
      waste incinerators.
AB  - Although incineration is an effective way of treating municipal solid waste
      (MSW), in many countries the potential health risks associated with stack
      emissions, particularly those of polychlorinated dibenzo-p-dioxins (PCDDs) and
      dibenzofurans (PCDFs), have become a cause of great controversy and concern.
      Given the interest and importance of this controversy, in the present paper a
      series of experimental data corresponding to a number of surveys made in the
      vicinity of three MSW incinerators (MSWIs) of Catalonia (Spain) are reviewed. In
      recent months, an adaptation to the EU legislation on pollutant emissions from
      the stack was carried out in these facilities. We assessed whether the pronounced
      reductions in the atmospheric PCDD/PCDFs emissions parallel the concurrent
      decreases in environmental matrices collected in the vicinity of the MSWIs. In
      comparison with other PCDD/PCDFs emission sources in the areas under direct
      influence of the MSWIs, the health risks from current emissions of PCDD/PCDFs by
      these incinerators would be of low significance for populations living in the
      neighborhood. For such populations, the daily intake of PCDD/PCDFs from direct
      and indirect (diet) exposure are currently within the rank recommended by the WHO
      as the maximum daily exposure to PCDD/PCDFs for non-carcinogenic adverse effects.

PMID- 12222740
TI  - An evaluation of waterborne disease surveillance in the European Union.
AB  - Surveillance systems to inform controls for waterborne disease (WBD) are
      important for the protection of public health. Member States of the European
      Union (EU) will soon be required to implement Directives and the Protocol on
      Water and Health for controlling WBD. The investigation reported here considers
      the consistency of surveillance systems across the EU. Eleven EU member states
      participated in a survey to determine the nature and range of practices used for
      monitoring WBD. Some WBD are notifiable in most countries surveyed, others are
      notifiable only in one country. Non-notifiable WBD are routinely monitored in
      five countries. Surveillance schemes are inconsistent, and the variable mandatory
      reporting among the Member States allows many WBD cases to remain unidentified.
      Nine replying countries had no legal definition for WBD outbreak. No country
      requires the reporting of anti-diarrhea medication sales for detecting outbreaks.

PMID- 12222741
TI  - Pathogenetic and diagnostic aspects of siliconosis.
AB  - Silicones have an adverse effect on human health well beyond that suggested by
      the recent superficial public controversy. The evidence for immune responses to
      injected/implanted silicones is extensive, detailed, often very specific, and not
      at all new. Comprehending the immunopathogenicity, realized and potential, of
      silicone has grown as our general understanding of the immune system has
      developed. Several major issues in furthering this comprehension pertain to the
      nature of the essential epitope, special risk of silicones to women, and
      definition of the chronic disease complex so evident clinically, one defying
      classification within currently traditional disease categories and states. The
      commentary presented here emphasizes the immunopathic evidence, explores the
      question of the essential epitope, estimates the minimal threshold of silicone
      load for immune reactivity, presents a profile of autoantibodies for siliconosis,
      and calls attention to specific silicone-based female contraceptive modalities.
      The silicone content of personal care products, not always revealed by retail
      package labeling, is explored as a potential sensitizing factor in the
      environment.

PMID- 12222742
TI  - Effects of intense exercise training on rainbow trout growth, body composition
      and metabolic responses.
AB  - Cultured fish are bound to experience a variety of potentially stressful
      situations. In principle, stress may be reduced by adapting fish to intense
      exercise. This article addresses the effects of chase-induced intense exercise
      training on rainbow trout. Training reduced fish growth and worsened their
      nutritional use of food, but had no effect on food intake, biometry or body
      composition, indicating that a significant fraction of the diet's energy was
      being used for exercising rather than growth. Regarding metabolic responses,
      training significantly counterbalanced lactate, glucose and cortisol plasma
      concentration increases induced by intense exercise, while completely abolishing
      that of plasmatic proteins. These data suggest that this type of training
      adversely affects fish growth and food conversion, whereas it improves their
      metabolic response capacity and reduces the stress component of forced exercise.

PMID- 12222743
TI  - Interactions between an alpha2-adrenergic antagonist and a beta3-adrenergic
      agonist on the expression of UCP2 and UCP3 in rats.
AB  - This experimental trial was devised to assess whether selective beta3-adrenergic
      receptor (AR) stimulation and simultaneous blockade of alpha2-AR would affect
      thermoregulation. With this purpose, the individual and combined administration
      of a beta-AR agonist, trecadrine, and an alpha2-AR antagonist, yohimbine, were
      evaluated. Yohimbine produced a marked decrease (p < 0.001) in body temperature
      one hour after administration (5 mg kg(-1), i.p.) and blocked the thermogenic
      effect of trecadrine (1 mg kg(-1), i.p.) when simultaneously administered.
      Uncoupling protein-2 expression in skeletal muscle was downregulated (p < 0.05)
      by trecadrine, while yohimbine had no effect. White adipose tissue UCP2 and
      muscle UCP3 were not modified by either trecadrine or yohimbine administration.
      Liver UCP2 mRNA expression was significantly decreased by yohimbine (p < 0.05).
      However, this downregulation does not seem to explain the reduction in
      temperature produced by yohimbine given the fact that trecadrine produced a
      similar downregulation of hepatic UCP2 (p < 0.05). The present work indicates
      that alpha2-AR antagonism blocks the thermogenic effects mediated by beta3-AR
      stimulation, contrary to our expectations, suggesting a possible interplay
      between both mechanisms. Moreover, these effects are not apparently explained by
      changes in UCP2 and UCP3.

PMID- 12222744
TI  - Effects of alpha-MSH on progesterone and nitric oxide release by cultured ovarian
      granulosa cells in experimental rat autoimmune oophoritis.
AB  - The peptide alpha-melanocyte-stimulating hormone (alpha-MSH) occurs within the
      pituitary, brain, skin, ovary and other tissues, and has potent anti-inflammatory
      activity. For this reason, we examined its effects on an autoimmune disease: the
      experimental autoimmune-oophoritis (EAO). We analyzed the effect of the peptide
      on the release of nitric oxide (NO) and progesterone from cultured ovarian
      granulosa (GL) cells at 0, 7, 14, 21 and 28 days after sensitization of the rats.
      On day 0 the progesterone levels were higher in estrous rats than those in
      proestrus and diestrus. The NO amount did not differ among the diverse days of
      the cycles. The administration of alpha-MSH induced a decrease of NO in estrus
      and diestrus, but did not affect progesterone release. The EAO rats showed a
      period of constant diestrus ranging from about 7 to 14 days after immunization.
      At the onset (day 7) and the end of this period (day 14), the NO significantly
      increased in estrous rats which was correlated with a reduction in progesterone
      concentration. This effect was reverted by alpha-MSH. At 21 and 28 days,
      progesterone release increased only when the rats were in proestrus, while NO
      production was similar to that on day 0. Administration of alpha-MSH reduced
      progesterone release when the rats were in proestrus and these results were
      correlated with an increase in NO only at day 14. The results obtained suggest
      that alpha-MSH could act as a modulator of EAO, specially when the rats are in
      estrus.

PMID- 12222745
TI  - Changes in plasma lipid composition induced by coconut oil. Effects of
      dipyridamole.
AB  - The comparative effects of 10-20% coconut oil feeding on fatty acid composition
      of the main lipid classes of chick plasma have been studied with and without
      simultaneous treatment with dipyridamole in order to clarify the hypolipidemic
      role of this drug. Coconut oil drastically increased the percentages of lauric
      and myristic acids in free fatty acid and triacylglycerol fractions, whereas
      these changes were less pronounced in phospholipids and cholesterol esters. The
      percentage of arachidonic acid was higher in plasma phospholipids than in the
      other fractions and was significantly decreased by coconut oil feeding. Linoleic
      acid, the main fatty acid of cholesterol esters, was drastically increased by
      coconut oil feeding. Changes induced by the simultaneous administration of
      dipyridamole were more pronounced in the phospholipids and cholesterol esters
      than in the other fractions. The fall observed in linoleic acid levels after
      dipyridamole treatment may be of interest for a lower production of its derived
      eicosanoids, especially in plasma phospholipids and cholesterol esters.

PMID- 12222747
TI  - Trans-resveratrol oral administration does not affect the enzymatic activities in
      rat small intestine.

PMID- 12222746
TI  - Improvement of DNA transfection with cationic liposomes.
AB  - The increasing use of cationic liposomes as vectors for DNA transfection of
      eukaryotic cells is due to its high efficiency and reproducibility. After the
      interaction of the DNA cationic-liposome complexes (DNA-CLC) with the plasma
      membrane, the entry into the cells delivers the DNA-CLC to the endosome-lysosome
      pathway where some of the DNA-CLC are degraded. The non-degraded DNA that escapes
      to the cytoplasm, still has to transverse the nuclear membrane to be transcribed
      and then translated. To improve the efficiency of the whole process, we can
      manipulate the DNA (sequences, promoters, enhancers, nuclear localisation
      signals, etc), the DNA-CLC (lipids) or the plasmatic, endosomal and/or nuclear
      cellular membranes (ultrasound, electroporation, Ca++, pH of the endosomes,
      mitosis, fusogenic peptides, nuclear localisation signals, etc). Most of these
      methods have been generally used individually but in combination, may greatly
      improve the efficiency and reproducibility of in vitro transfection. While much
      of this work remains yet to be done and present results further explored, the
      application of these efforts is essential to the future development of new gene
      therapy strategies.

PMID- 12222748
TI  - Cytokine effect on intestinal galactose absorption.

PMID- 12222749
TI  - Determinants of resting energy expenditure in obese and non-obese children and
      adolescents.
AB  - Resting energy expenditure (REE) is the largest component of total daily energy
      expenditure. Objectives of this study were to examine whether differences in REE
      exist after obesity develops in a group of children and adolescents, and to
      determine the effects of body composition, gender, age, pubertal development and
      parental obesity on REE. In 116 Caucasian children and adolescents (57 obese and
      59 non-obese), aged 7.8 to 16.6 years, REE was assessed by open-circuit indirect
      calorimetry and different anthropometric variables and bioelectrical impedance
      were obtained (weight, height, skinfold thicknesses, waist and hip
      circumferences). Anthropometric indices and body compartments were calculated:
      the body mass index, surface area (SA), fat-free mass (FFM), fat-mass (FM) and
      percentage of FM. Differences between obese and non-obese subjects were tested
      and stepwise multiple regression analysis was performed with REE as dependent
      variable. Results show that REE was significantly higher in obese than in non
      obese children and adolescents but REE/FFM ratio was not significantly different
      between these groups. In the non-obese group, FFM explained 73.1% of the
      variability in REE and gender, age and SA added 3.8%, 2.6%, and 2.6% to it,
      respectively. In the obese group, FFM was also the most powerful predictor of REE
      with 72.3%, followed by waist circumference and age with 2.5% and 2.1%,
      respectively. These results show that REE differences between obese and lean
      children do not seem to justify the maintenance of obesity. The main determinant
      of REE is FFM in both groups. No significant contribution of FM, pubertal
      development or parental obesity in REE was found in children and adolescents.

PMID- 12222750
TI  - Pharmacokinetics of fluvoxamine in relation to CYP2C19 phenotype and genotype.
AB  - OBJECTIVE: To evaluate the pharmacokinetics of fluvoxamine (FLV) in poor
      metabolizers (PMs) versus extensive metabolizers (EMs) of cytochrome P450
      (CYP)2C19. METHODS: This was a prospective, open-label study conducted at the
      Clinical Research Unit School of Pharmacy. Fifty-seven healthy, nonsmoking
      volunteers aged 21-40 years participated. Subjects abstained from caffeinated
      products 12 hours prior to and during each testing period. To assess CYP2C19
      activity, blood samples were collected from each subject prior to and two hours
      after a single dose of omeprazole 20 mg. Once PMs were identified, a sample
      population of EMs were selected for comparison between the two groups regarding
      FLV disposition. A single 100 mg FLV dose was given to EMs and PMs; blood samples
      for FLV analysis were obtained prior to drug administration and 0.5, 1, 2, 3, 4
      6, 8, 12 and 24 hours later. A blood sample one day prior to FLV administration
      was also obtained for CYP2C 19 and CYP2D6. RESULTS: Four PMs were identified with
      the omeprazole phenotype probe and had a mean +/- SD hydroxylation index of 1.335
      +/- 0.271. Nine EMs were selected based upon a hydroxylation index between 0.100
      and 0.400 (mean 0.193 +/- 0.079). FLV pharmacokinetic parameters (AUC,
      elimination half-life, Cmax and Tmax) did not significantly differ between the
      two groups. Genotype analysis for CYP2C19 revealed a mutant allele for the *2
      which confirmed phenotype detection of PM status. Genotype analysis for CYP2D6*3
      and *4 alleles showed that all PMs of CYP2C19 were EMs of CONCLUSIONS: FLV
      disposition and dosing is unlikely to be affected by CYP2C19 polymorphism.

PMID- 12222751
TI  - Decreased hepatic drug metabolising enzyme activity in rats with nitrosamine
      induced tumours.
AB  - N-Methyl N-benzyl nitrosamine (MBNA), which requires P450-dependant activation to
      be mutagenic, has been shown to produce squamous cell carcinoma of rat
      oesophagus. The aim of this study was to determine the effects of tumour
      induction on hepatic cytochrome P450 (CYP) and phase II enzyme activity. Female
      Wistar rats were given MBNA (2.5 mg/kg) by gavage, twice weekly for 12 weeks. At
      the end of 12 weeks they were sacrificed; livers and oesophagi were removed. The
      activity of hepatic CYP and phase II enzymes was determined by incubation of
      liver microsomes with appropriate CYP substrates. All rats receiving MBNA
      developed oesophageal lesions. Hepatic CYP1A2 activity (phenacetin 5 microM) in
      tumour-bearing rats was significantly decreased to 53% of the controls (p <0.05).
      CYP2E1 (p-nitrophenol hydroxylase), CYP2D (debrisoquine hydroxylase) and CYP3A
      (quinine hydroxylase) activity was significantly (p <0.05) reduced. Microsomal
      UDP-glucuronosyl transferase activity was also found to be markedly decreased
      while glutathione-S-transferase activity remained almost unchanged. Alteration of
      the activities of drug metabolising enzymes in rats with chemically induced
      tumours could be an important factor in determining resistance or susceptibility
      to xenobiotics and antitumour drugs.

PMID- 12222752
TI  - Molecular orbital calculations and nicotine metabolism: a rationale for
      experimentally observed metabolite ratios.
AB  - The results of molecular orbital calculations and molecular modelling studies on
      nicotine are reported. It is shown that the product ratio of nicotine metabolism
      can be directly related to HOMO electron densities on the relevant hydrogen atoms
      associated with oxidation sites in S-nicotine. In addition, molecular modelling
      of nicotine within the putative active site of CYP2A6, the enzyme most closely
      associated with nicotine metabolism, indicates that the substrate is orientated
      for oxidation at the 5'-position via a combination of hydrogen bonding and pi-pi
      stacking interactions. Alternative routes of metabolism may require rotation of
      the pyrrolidine ring system and could, therefore, involve a degree of re
      orientation of the nicotine molecule which is energetically less favourable than
      the modelled interaction indicating formation of cotinine via 5'-oxidation.

PMID- 12222753
TI  - Effect of cephalexin on the pharmacokinetics of metformin in healthy human
      volunteers.
AB  - The purpose of this study was to assess the effect of a single dose of cephalexin
      on the pharmacokinetics of metformin in healthy human volunteers. A 2 x 2 double
      blind randomized crossover study was conducted in 12 healthy human volunteers.
      Each subject received orally either 500 mg of metformin with a placebo or a
      combination of 500 mg of metformin and 500 mg of cephalexin. Serum and urine
      levels of metformin were estimated by a validated HPLC method. The systemic
      disposition of metformin was altered by the co-administration of cephalexin.
      Cephalexin increased Cmax and AUC by an average of 34% and 24%, respectively, and
      reduced renal clearance to 14%. The renal clearance of metformin was reduced in a
      time-dependent manner in the presence of cephalexin. Hence, it is concluded that
      cephalexin inhibits the renal tubular secretion of metformin resulting in higher
      circulating serum concentrations.

PMID- 12222754
TI  - Prediction of clearance in humans from in vitro human liver microsomes and
      allometric scaling. A comparative study of the two approaches.
AB  - The objective of this study was to evaluate whether the predicted clearance of a
      drug in humans from in vitro human liver microsomes was comparable with the
      predicted clearance in humans obtained by allometric scaling. Sixteen drugs were
      randomly selected from the literature and their hepatic clearances were predicted
      using human liver microsomes. For allometric scaling at least three animal
      species were used and three methods were utilized to generate allometric
      equations to predict the clearance in humans: (i) clearance vs body weight
      (simple allometry); (ii) product of the clearance and maximum life-span potential
      (MLP) vs body weight; and (iii) the product of clearance and brain weight vs body
      weight. The choice of one of the methods was based on the 'rule of exponents' as
      described by Mahmood and Balian /2,3/. The results of this study indicated that
      the use of human liver microsomes to predict hepatic clearance in humans may not
      provide reliable predictions. On the other hand, the prediction of clearance in
      humans using allometric scaling combined with the 'rule of exponents' can provide
      comparatively better prediction of clearance in humans.

PMID- 12222755
TI  - Comparison of the fracture resistance of six denture base acrylic resins.
AB  - Fracture strength of denture base resins is of great concern, and many approaches
      have been used to strengthen acrylic resin dentures. Fracture resistance of six
      commercially available acrylic resin denture base materials were compared,
      through impact and transverse strength tests. Three rapid heat-polymerised resins
      (QC 20, Meliodent and Trevalon), two high-impact strength resins (Trevalon Hi and
      Lucitone 199) and a strengthened injection-moulded acrylic resin (SR Ivocap plus)
      were included in the study. Twenty acrylic resin test specimens were fabricated
      from each resin. For impact strength test, ten notched specimens were tested in a
      Charpy-type impact tester. The other ten specimens were used for transverse
      strength tests, deflection and modulus of elasticity values were also determined,
      which were assessed with three-point bending tests using an Universal Testing
      Machine. Impact test values showed significant differences among acrylic resins
      (F= 4.817 p = 0.0). SR Ivocap resin showed the highest impact strength values,
      followed by Trevalon Hi and Lucitone 199. The transverse strength test values
      were not significant when six acrylic resins were compared (F= 1.705 p = 0.151).
      High-impact resins can be recommended to increase the impact strength of denture
      base. If the cause of fracture is mechanical or anatomical, strengthened acrylic
      resins and conventional acrylic resins have similar fracture resistance.

PMID- 12222756
TI  - Enhanced wear resistance of ball-and-socket joints of dental implants by means of
      titanium gaseous nitriding.
AB  - The aim of this research is the surface hardening of the ball-and-socket joint of
      dental implants by means of heat treatments in order to obtain titanium nitrides.
      These nitrides minimize the wear of the titanium used in prosthesis. In this
      paper the optimum heat treatment, the hardness and the wear resistance are
      described in relation to the ball-and-socket joint without heat treatment.

PMID- 12222757
TI  - Endothelial cell seeding of a 4-mm I.D. polyurethane vascular graft.
AB  - We evaluated the extent (luminal coverage) of the endothelial cell (EC)
      lining/neointimal development and the thromboresistance of electrostatically EC
      seeded small diameter ChronoFlex-polyurethane vascular grafts. The evaluation
      consisted of harvesting autologous, canine jugular vein ECs, electrostatically
      seeding the polyurethane grafts (4-mm I.D., length = 6 cm) with the harvested
      ECs, implanting the grafts in a canine femoral artery model for four to six
      weeks, and excising the grafts for histological and scanning electron microscopy
      evaluations. Results of the histological evaluation (mid-graft region only)
      indicated that electrostatic EC seeding led to neointimal development and to
      minimal to no thrombus formation within the EC seeded grafts. The unseeded
      control grafts resulted in no neointimal development and substantial thrombus
      formation on the graft luminal surfaces. Scanning electron microscopy examination
      demonstrated a mature, confluent endothelium with a "cobblestone" appearance on
      the EC seeded graft luminal surface after six weeks. We conclude that
      electrostatic EC seeding enhanced the development of a neointima and reduced the
      incidence of thrombosis in polyurethane grafts implanted in a canine femoral
      artery model.

PMID- 12222758
TI  - Hemocompatibility of medical connectors with biopassive or bioactive surface
      coatings.
AB  - Although medical connectors compose very small parts of the extracorporeal
      circulation (ECC) system they represent a critical localization where early
      thromboembolic processes can manifest. In the present study we modified an in
      vitro closed-loop model with fresh human whole blood for the preclinical
      evaluation of the hemocompatibility of three types of medical connectors: non
      coated (control); with silicone-, and heparin-coating. Each single loop consists
      of five polycarbonate connectors joined together by five pieces of silicone
      tubes. Thrombin-antithrombin-III, beta-thromboglobulin (beta-TG), PMN-Elastase,
      terminal complement complex, CD 11b expression, and surface-absorbed fibrinogen
      were measured. After 1 and 2 h recirculation, platelet loss, release of beta-TG,
      and adsorption of fibrinogen were significantly higher (p<0.05) within the non
      coated connectors compared to the silicone- and heparin-coated groups. Following
      this experiment, the connectors were filled again with fresh heparinized whole
      blood from the same donor to evaluate the influence of prior blood contact. Here,
      the activation of platelets and coagulation was dependent on the duration of the
      blood preincubation period. Probably, the coated surfaces possess a reduced, or
      selective adsorption of plasma proteins, which in turn leads to a faster creation
      of a blood-friendly secondary superficial membrane, and prevents a further
      denaturation and hence activation of the adsorbed proteins.

PMID- 12222759
TI  - Volume variations of bone tissue after undergoing different physical and chemical
      treatments.
AB  - Both autogenic and allogenic bone has been employed through different surgical
      procedures to fill different defects or as osteosynthesis materials. Some
      physical and/or chemical treatments are usually necessary before its use. Since
      bone volume is important from a surgical point of view, the present study was
      designed to analyse its possible variations when subjected to certain procedures.
      Screws made of bovine cortical bone were autoclaved in different conditions
      regarding time and vacuum (A1-A2), cryopreserved, demineralised, enzymatically
      digested and rehydrated. The samples were measured before and after every
      treatment. Sterilisation caused a volume reduction more marked with method A1
      than A2 whereas freezing allowed to obtain the original size. No volumetric
      changes were registered after demineralisation and enzymatic digestion.
      Rehydration significantly increased their volume already during the first hour
      but the maximum value was reached at 24 h. Thus, autoclaving was the only
      treatment able to reduce the bone volume whilst freezing and rehydration allowed
      the samples to return to their original size.

PMID- 12222760
TI  - Ocular hypotension induced by electroacupuncture.
AB  - The purpose of this study was to investigate the effects of electroacupuncture
      (EA) on aqueous humor dynamics in rabbits. EA stimulation was performed through
      two acupuncture needles placed in close proximity to the sciatic nerve. The sites
      of needle entry were anesthetized. After 1 hr of EA stimulation, intraocular
      pressure (IOP) decreased and was accompanied by reductions of blood pressure and
      aqueous humor flow rate. The maximum reduction of IOP was 9 mmHg at 3 hr and
      decreases in norepinephrine and dopamine levels in aqueous humor occurred
      simultaneously. In addition, EA stimulation induced an 8-fold increase of
      endorphin levels in aqueous humor. Ocular hypotension induced by EA lasted for
      more than 9 hrs and was antagonized by naloxone pretreatment. Furthermore, the EA
      induced ocular hypotension was reduced markedly in sympathetically denervated
      eyes compared with the response of intact, normal eyes. Antagonism of EA-induced
      ocular hypotension by naloxone, suppression of aqueous humor flow and
      catecholamine levels by EA and elevation of endorphin levels in aqueous humor by
      EA indicate that opioids/opiate receptors are involved in modulating ocular
      hydrodynamics in response to EA.

PMID- 12222761
TI  - Postoperative subconjunctival mitomycin-C injection after non-penetrating
      glaucoma surgery.
AB  - PURPOSE: To evaluate subconjunctival mitomycin C (MMC) injection efficacy and
      safety in patients with failing glaucoma non-penetrating filtering blebs.
      METHODS: Twenty-eight eyes were consecutively recruited for this study. Only one
      eye for each patient was randomly selected. All the recruited patients had
      glaucoma and uncontrolled intraocular pressure after a non-penetrating filtering
      glaucoma surgery and/or a pathological aspect of the filtering bleb (i.e.,
      vascularized and/or encysted). One or more MMC injections were performed under
      the conjunctiva closed to the bleb to improve filtration. Local effects and
      complications of subconjunctival MMC injections were analyzed. RESULTS: Out of
      the 28 patients, 21 (75%) had MMC also applied intraoperatively. The mean
      postoperative IOP before MMC injections was 17 +/- 6.6 mmHg. The final IOP after
      MMC injections was 13.9 +/- 2.9 mmHg after a mean follow-up of 6 months. A total
      of 67 subconjunctival MMC injections were performed with a mean of 2.9 (ranging
      from 1 to 5) injections per patient. The only complication found to be possibly
      related to MMC injections was two cases of corneal Dellen. CONCLUSION: From these
      preliminary results, subconjunctival MMC injections in selected cases appear to
      be not only safe but also effective in promoting further the postoperative IOP
      drop.

PMID- 12222762
TI  - Agonist activity of bimatoprost, travoprost, latanoprost, unoprostone isopropyl
      ester and other prostaglandin analogs at the cloned human ciliary body FP
      prostaglandin receptor.
AB  - We have determined the agonist activity of a number of natural prostaglandins and
      prostaglandin analogs at the FP prostaglandin receptor cloned from a human
      ciliary body cDNA library using phosphoinositide (PI) turnover assays. Travoprost
      acid (EC50 = 3.2 +/- 0.6 nM) was the most potent agonist in these cells followed
      by bimatoprost free acid (17-phenyl-trinor PGF2alpha; EC50 = 5.8 +/- 2.6 nM),
      fluprostenol (EC50 = 6.1 +/- 1.5 nM), and latanoprost free acid (PHXA85; EC50 =
      54.6 +/- 12.4 nM) which was 17-fold weaker (p < 0.001) than travoprost acid.
      Unoprostone and S-1033 were significantly (p < 0.001) weaker than travoprost
      acid. The amide prodrug, bimatoprost (EC50 = 694 +/- 293 nM), activated this FP
      receptor with an intermediate potency. The isopropyl ester prodrugs, travoprost
      (EC50 = 42.3 +/- 6.7 nM), latanoprost (EC50 = 126 +/- 347 nM) and unoprostone
      isopropyl ester (EC50 = 9,100 +/- 2,870 nM), also exhibited FP agonist activity.
      However, other compounds such as PGI2, bradykinin, histamine, and serotonin were
      inactive. The agonist activities of bimatoprost, unoprostone (UF-021),
      fluprostenol and acids of travoprost and latanoprost were antagonized by AL-8810
      (11beta-fluoro- 15-epi-15-indanyl-PGF2alpha), an FP-receptor-selective antagonist
      (Ki = 1.0 - 2.1 microM; n = 3). These studies have demonstrated, for the first
      time, agonist activities of the currently known and marketed ocular hypotensive
      prostaglandin analogs at the cloned human ciliary body FP prostaglandin receptor.

PMID- 12222763
TI  - Formulation effects on ocular absorption of brimonidine in rabbit eyes.
AB  - Purite (stabilized oxychloro complex) and benzalkonium chloride (BAK) are
      preservatives. We investigated formulation effects on ocular absorption of
      brimonidine in rabbit eyes. The formulations compared were: Alphagan (0.2%
      brimonidine tartrate/0.005% BAK, pH 6.4), Brimonidine-Purite (0.2% brimonidine
      tartrate/0.005% Purite, pH 7.2), and Brimonidine-PF (0.2% brimonidine tartrate,
      preservative-free (PF), pH 6.4) solutions. The study was conducted in a cross
      over fashion; albino rabbits (n = 18) were given a single 35 microl drop of each
      test formulation in each eye. Aqueous humor samples were collected at selected
      times post-dose from subgroups of 2 rabbits per timepoint and analyzed for
      brimonidine concentrations by LC-MS/MS. The AUC and Cmax were calculated. The
      results showed rapid ocular absorption of brimonidine, with peak concentrations
      at 0.33-1 hr. The AUC(0-5hr) values were 3.78 +/- 0.38, 2.77 +/- 0.22, and 2.49
      +/- 0.22 microg-hr/ml (mean +/- SEM) for Brimonidine-Purite, Alphagan and
      Brimonidine-PF, respectively. The corresponding Cmax values were 2.69 +/- 0.72,
      1.74 +/- 0.13, and 1.24 +/- 0.22 microg/ml (mean +/- SEM). Brimonidine-Purite
      provided significantly higher AUC(0-5hr) than Alphagan (p < 0.05). No statistical
      significant difference in AUC(0-5hr) was found between Alphagan and Brimonidine
      PF. In conclusion, 0.2% Brimonidine-Purite was 1.4 and 1.5 times more ocularly
      bioavailable in rabbits than 0.2% Alphagan and 0.2% Brimonidine-PF, respectively.

PMID- 12222764
TI  - Pharmacology of serotonin receptors modulating electrically-induced [3h]
      norepinephrine release from isolated mammalian iris-ciliary bodies.
AB  - The pharmacology of prejunctional serotonin (5-HT) heteroreceptors that regulate
      the release of norepinephrine (NE) was studied in isolated bovine and human iris
      ciliary bodies. The effect of exogenous 5-HT and various 5-HT receptor agonists
      was examined on the release of [3H]-norepinephrine ([3H]NE). Both 5-HT and m
      chlorophenyl-biguanide (m-CPBG) caused enhancement in the field-stimulated
      release of [3H]NE from bovine tissues whereas 5-carboxamidotryptamine (5-CT) had
      no such effect. On the other hand, 8hydroxy-dipropylaminotetralin (8-OH-DPAT),
      caused a significant dose-related inhibition of evoked [3H]NE release. In human
      iris-ciliary bodies, 5-HT caused an inhibitory response on electrically-evoked
      [3H]NE release at low concentrations but produced an excitatory action at
      concentrations greater than 3 microM. To further confirm the nature of the
      prejunctional 5-HT heteroreceptors regulating [3H]NE release, effects of 5-HT3, 5
      HT6 and 5-HT7 receptor antagonists were examined on a standard response to 5-HT.
      All antagonists examined caused a concentration-dependent inhibition of the
      response elicited by the standard 5-HT-induced response with the following rank
      order of potency (as measured by IC30 values): MDL-72222 >> SB-258719 > RO-04
      690. We conclude that the excitatory prejunctional 5-HT heteroreceptors present
      in bovine iris-ciliary bodies belong to the 5-HT3 receptor subtype.

PMID- 12222765
TI  - Corneal protection by the ocular mucin secretagogue 15(S)-HETE in a rabbit model
      of desiccation-induced corneal defect.
AB  - The mucin secretagogue 15(S)-HETE was found to stimulate glycoprotein secretion
      in human ocular tissue at submicromolar concentrations in the present studies.
      Therefore, the ability of topically applied 15(S)-HETE to preserve corneal
      integrity was investigated in a rabbit model of desiccation-induced corneal
      defect. Desiccation-induced corneal injury was elicited in anesthetized rabbits
      by maintaining one eye open with a speculum. Corneal staining and corneal
      thickness changes were determined immediately following desiccation. 15(S)-HETE
      dose-dependently reduced corneal damage (ED50 = 120 nM) during a two-hour
      desiccation. Corneal staining was unchanged relative to control using a 1 microM
      dose of 15(S)-HETE. Through four hours of desiccation, 15(S)-HETE (500 nM)
      decreased corneal staining by 71% and completely prevented corneal thinning.
      15(S)-HETE (1 microM) was significantly more efficacious than an artificial tear
      product over the 4-hour desiccation period. There was no evidence of
      tachyphylaxis following repeated topical ocular dosing of 15(S)-HETE. These
      studies demonstrate that 15(S)-HETE stimulates ocular mucin secretion in vitro
      and effectively protects the cornea in a rabbit model of desiccation-induced
      injury. The results suggest that the ocular mucin secretagogue 15(S)-HETE may
      have therapeutic utility in dry eye patients, alleviating corneal injury and
      restoring corneal integrity.

PMID- 12222766
TI  - INS365 suppresses loss of corneal epithelial integrity by secretion of mucin-like
      glycoprotein in a rabbit short-term dry eye model.
AB  - P2Y2 receptor agonists, like UTP and ATP, stimulate mucin secretion from goblet
      cells in vitro. Therefore, mucin stimulants could be good candidates for the
      treatment of dry eye syndrome because mucin increases the tear film stability and
      protects against desiccation of ocular surface. INS365 is a more stable P2Y2
      receptor agonist than UTP. In the present study, we evaluated, in normal rabbit
      eyes, its effectiveness to release mucin from goblet cells and to protect the
      corneal damage induced by desiccation. For mucin secretion, impression cytology
      was performed following the instillation of INS365 solution or saline into the
      conjunctival sac. The specimens were stained with periodic acid and Schiff (PAS)
      reagent, and then the staining area was calculated using computer software.
      INS365 dose-dependently decreased the PAS staining area of conjunctival goblet
      cells from 2 to 15 min post-application. Furthermore, we utilized the rabbit
      short-term dry eye model to evaluate if INS365 eyedrops could protect against any
      of the damage produced by blockage of blinking with ocular speculum. INS365
      significantly suppressed corneal damage at concentrations of more than 0.1% w/v.
      These results suggest that this P2Y2 agonist is a good candidate for the
      treatment of dry eye disease.

PMID- 12222767
TI  - Differences in bioavailability of fornixes in different head positions.
AB  - Clinically, in infectious corneal or scleral ulcers, we have found some upper
      lesions to show a poorer response to eye-drops than lower lesions. This clinical
      observation stimulated our interest to investigate the differences of drug
      bioavailability in upper and lower fornixes in three different head positions.
      Seventeen people, 34 eyes, were enrolled in this study. There were three head
      positions for 0.1% fluorescein eye-drops application, including sitting, supine,
      and supine-with-chin-up. Schirmer's test paper was placed in the fornix to absorb
      the fluorescein, and the bioavailability was analyzed by fluorescence
      spectrophotometry. Fluorescein bioavailability of upper-and-lower fornixes were
      1.30 x 10(-5)% and 7.33 x 10(-5)%, 3.93 x 10(-5)% and 9.57 x 10(-5)%, and 23.19 x
      10(-5)% and 5.09 x 10(-5)% in sitting, supine, and supine-with-chin-up positions,
      respectively. Bioavailability of the lower fornix was significantly higher than
      that of the upper in the sitting position, and the bioavailability of the upper
      fornix was significantly higher than for the lower fornix in the supine-with-chin
      up position. The bioavailability of the upper fornix in the supine-with-chin-up
      position was significantly higher than that in the sitting and supine positions,
      respectively. The total fluorescein bioavailability of both fornixes in the
      supine-with-chin-up position was significantly higher than that in the sitting
      position. We postulate that different head positions can influence drug
      bioavailability in the upper and lower fornixes. Ocular surface lesions in
      different sites may require different head positions during eye-drop application
      to obtain the best therapeutic results.

PMID- 12222768
TI  - Role of apoptosis in the cytotoxic effect mediated by daunorubicin in cultured
      human retinal pigment epithelial cells.
AB  - To investigate whether apoptosis is involved in the therapeutic effect of
      daunorubicin on proliferative vitreoretinopathy (PVR), cultured human retinal
      pigment epithelial cells (RPE) were exposed to a cytotoxic dose of 180 microg/l
      daunorubicin. After 12-hour treatment with the drug and 24-hour prolonged post
      incubation in the drug-free medium, progressive condensation, shrinkage of
      cytoplasm and nucleus, and fragmented nuclei were identified by light and
      electron microscopy. TUNEL assay showed the characteristic apoptotic patterns of
      circumscribed clumps and sometimes even dark masses in nuclei. The expression of
      bax protein was enhanced, and the integral optical density values for
      immunocytochemical expression of bax protein increased by 22.0% in the drug
      treated group (P < 0.05). The results demonstrated the pivotal role of apoptotic
      mechanism in the cytotoxic effect mediated by daunorubicin, and confirmed the
      relationship between the drug-induced apoptosis and overexpression of bax
      protein. It suggested that the upregulation of bax mediated by daunorubicin could
      lead to the onset of apoptosis, and therefore contribute to its therapeutic
      mechanisms for the treatment of PVR.

PMID- 12222769
TI  - Levels and profiles of PCDDs, PCDFs and cPCBs in Belgian breast milk. Estimation
      of infant intake.
AB  - Congener-specific analyses of polychlorinated dibenzo-p-dioxins (PCDDs),
      polychlorinated dibenzofurans (PCDFs) and non-ortho (coplanar) polychlorinated
      biphenyls (cPCBs) were performed on 20 non-pooled breast milk samples collected
      in or close to an industrial area of Wallonia (Belgium). PCDD/F concentrations
      ranged between 16.0 and 52.1 pg TEQ/g fat, with a mean value of 29.4 pg TEQ/g
      fat. If coplanar PCBs (77, 126, 169) are included in TEQ calculations, levels
      ranged between 22.2 and 100.2 pg TEQ/g fat, with a mean value of 40.8 pg TEQ/g
      fat. It appears that 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, 2,3,4,7,8-PeCDF and PCB-126
      account for more than 90% of the TEQ. Estimated PCDD/F dietary intake is 76 pg
      TEQ/kg body weight (bw)/day. This value is almost 20 times higher than the World
      Health Organization tolerable daily intake. A value of 103 pg TEQ/kg bw/day
      represents the intake of PCDDs, PCDFs and cPCBs (no mono-ortho PCBs included).

PMID- 12222770
TI  - Theoretical study of the dechlorination reaction pathways of octachlorodibenzo-p
      dioxin.
AB  - The dechlorination reaction pathways of 1,2,3,4,6,7,8,9-octachlorodibenzo-p
      dioxin (OCDD) by the hydrogen atom are investigated by the density-functional
      theory B3PW91 method. The dechlorination reactions have large exothermicity and
      small activation energies. The activation energies (approximately 5 kcal/mol) of
      the sigma-complex formation due to the hydrogen addition are lower than those
      (approximately 9 kcal/mol) of the direct chlorine abstraction. It is suggested
      that the sigma-complex plays an important role in the reactions, although it has
      scarcely been shown in previous studies of the dechlorination of dioxins. The
      sigma-complex formation is favored at low temperatures and the chlorine
      abstraction is favored at high temperatures. Furthermore, it is found that the
      lateral positions have a marginal preference over the longitudinal positions. The
      dechlorination of OCDD by the hydrogen atom is thus not likely to result in a
      dominant formation of the laterally substituted toxic congeners.

PMID- 12222771
TI  - PCDD/Fs emissions inventory in the Lombardy Region: results and uncertainties.
AB  - The results of an assessment study of both industrial and non-industrial dioxin
      and furan (PCDD/Fs) emissions in the Lombardy Region (Italy) are outlined below.
      The main data source refer to 1997, and are compiled from the Lombardy Emissions
      Inventory (developed under the framework of the Regional Air Quality Plan)
      together with documented emissions factors available. Due to the uncertain nature
      of the emissions assessment, results are provided as a most probable value within
      a given range. Total PCDD/Fs emissions in Lombardy average 33 g I-TEQ y(-1),
      ranging from minimum 13 g I-TEQ y(-1) to maximum 88 g I-TEQ y(-1). The main
      PCDD/Fs sources are waste incineration, electric arc furnace for steel
      production, vehicle diesel combustion and residential wood combustion.
      Incineration emission factors are expected to decrease over the period 2005-2010,
      in compliance with legal requirements. This will prioritize control over the
      remaining main PCDD/Fs contributors. Due to limited information available
      concerning this data, the accuracy of which is uncertain, further research is
      needed to evaluate the future role of these sources.

PMID- 12222772
TI  - Debromination of hexabromobenzene by its co-grinding with CaO.
AB  - A hexabromobenzene (HBB, C6Br6) powder was subjected to co-grinding with excess
      CaO powder in air using a planetary ball mill to investigate mechanochemical
      debromination of the HBB sample. The reaction proceeds smoothly with an increase
      in both grinding time and molar ratio of CaO addition. The co-grinding enables us
      to debrominate HBB, forming CaBr2, C and CaCO3 besides excess CaO in the product.
      CaBr2 in the product tends to absorb moisture from the atmosphere to form CaBr2 x
      nH2O. The reaction yield is quantitatively evaluated by measuring the amount of
      water-soluble bromide through water washing and the amount of unreacted HBB
      through toluene washing. It is found that almost 100% of debromination is
      achieved by 6 h grinding with the molar ratio kept constant at 2:1. Radicals are
      detected in the ground products, possibly due to rupture in the covalent bonds of
      C-C and C-Br in HBB.

PMID- 12222773
TI  - Feeding trial on rainbow trout: comparison of dry fish feed and Baltic herring as
      a source of PCDD/Fs and PCBs.
AB  - Fish is an important source of dietary intake of polychlorinated dibenzo-p
      dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs). To
      assess bioaccumulation of PCDD/Fs and PCBs in farm-raised fish, rainbow trout
      were fed with either Baltic herring or dry fish feed. Baltic herring feed had a
      PCDD/F sum concentration of 125 ng kg(-1) dry weight (d.w.), and dry fish feed
      contained 18.2 ng kg(-1) d.w. of PCDD/Fs. The PCB concentrations of Baltic
      herring and dry fish feed were 188 and 48.7 microg kg(-1) d.w., respectively.
      After feeding with Baltic herring for 4 months, the PCDD/F concentration of the
      rainbow trout fillet was 27.3 ng kg(-1) fresh weight (f.w.), which was 7.0-fold
      higher than the initial concentration. The PCDD/F concentration and congener
      profile in rainbow trout had become almost the same as in Baltic herring. PCDD/Fs
      were accumulated in the fillet with an efficiency of 21%. Feeding of rainbow
      trout with dry fish feed resulted in a PCDD/F concentration of 8.08 ng kg(-1)
      f.w., denoting a 2.1-fold increase from the initial level. The accumulation
      efficiency was 29%. Time trends in PCB concentrations followed those of PCDD/Fs.
      After 4 months, the PCB sum concentration in herring-fed rainbow trout was 94.4
      pg kg(-1) f.w., whereas in dry fish feed-fed rainbow trout it was 38.6 microg kg(
      1) f.w. Accumulation efficiencies of PCBs were higher than those of PCDD/Fs.
      Based on the accumulated PCDD/F and PCB concentrations, it was estimated that
      frequent consumption of rainbow trout fed with Baltic herring could lead to a
      human daily intake that exceeds the recommendation of WHO.

PMID- 12222774
TI  - Distribution and levels of brominated flame retardants in sewage sludge.
AB  - One hundred and sixteen sewage sludge samples from 22 municipal wastewater
      treatment plants in Sweden were analysed for brominated flame retardants.
      Polybrominated diphenyl ethers (PBDEs) were in the range n.d.-450 ng/g wet
      weight, tetrabromobisphenol A (TBBPA) varied between n.d. and 220 ng/g wet
      weight, 2,4,6-tribromophenol was in the range n.d.-0.9 ng/g wet weight and
      polybrominated biphenyls were not detected (except for a possible analytical
      interference). There was a significant variation in the samples among plants.
      Influence from industries and other local sources can therefore be assumed. The
      correlation pattern indicated contribution from three different types of
      technical products; composed of either low-brominated PBDEs, decaBDE or TBBPA.

PMID- 12222775
TI  - Persistent organochlorine pollutants in human serum of 50-65 years old women in
      the Flanders Environmental and Health Study (FLEHS). Part 1: Concentrations and
      regional differences.
AB  - In 1999, a campaign of the Flemish Ministry of Health, Belgium was set up to
      assess pollutant concentrations and related health effect biomarkers in humans
      living in two regions of Flanders. The study was called the 'Flemish Environment
      and Health Study' (FLEHS). One of the goals was to measure present concentrations
      of persistent organochlorine pollutants in a Flemish population and to compare
      values obtained from pooled and individual serum samples. Concentrations of
      selected organochlorine pesticides, polychlorinated biphenyls (PCB) and
      polychlorinated dibenzo-p-dioxins (PCDD) and furans (PCDF) were measured by gas
      chromatography-mass spectrometry. TEQ values were also assessed by Chemical
      Activated LUciferase gene eXpression (CALUX) bioassay. The study population
      consisted of 200 women between 50 and 65 years living in two areas of Flanders,
      Belgium. Because of the large volumes serum needed for all measurements, the
      concentrations of organochlorines were measured in 47 pooled serum samples
      originating from these women. The concentrations of the indicator PCBs (359.8
      ng/g fat) and organochlorine pesticides (hexachlorobenzene, p,p'
      dichlorodiphenyldichloroethylene, p,p'-dichlorodiphenyl-trichloroethane, lindane
      and pentachlorophenol), were comparable to those found in other European
      countries. The concentrations of PCDD/PCDFs showed another picture. With a median
      value of 48 pg WHO-TEQ/g fat, the women had 2-fold higher levels than a
      comparable age group from Germany examined in 1996. The mean total WHO-TEQ
      including PCDD/F, non-ortho and mono-ortho PCBs was 72.7 pg WHO-TEQ/g fat,
      whereas the CALUX-TEQ mean value was only 35.0 pg TEQ/g fat. In order to assess
      the pooling procedure, indicator PCBs and CALUX-TEQs were measured in all 200
      individuals that were integrated in the pools. The measured values were
      comparable to the pool results: 390.0 ng/g fat and 41.6 pg TEQ/g fat
      respectively. It was concluded that pooling of serum samples offers the
      possibility to measure exposure in the whole study population on a more cost
      effective way. However, because of statistical power loss and no possibility of
      confounder adjustment, pooling is not the most effective way to study regional
      differences.

PMID- 12222776
TI  - Persistent organochlorine pollutants in human serum of 50-65 years old women in
      the Flanders Environmental and Health Study (FLEHS). Part 2: Correlations among
      PCBs, PCDD/PCDFs and the use of predictive markers.
AB  - In 1999, the FLEHS was set by the Flemish Ministry of Health, Belgium to assess
      pollutant concentrations and related health effect biomarkers in humans living in
      Flanders. Concentrations of selected organochlorine pesticides, polychlorinated
      biphenyls (PCB) and polychlorinated dibenzo-p-dioxins (PCDD) and furans (PCDF)
      were measured by gas chromatography-mass spectrometry and Chemical-Activated
      LUciferase gene eXpression (CALUX) bioassay in 47 serum pools of 200 women
      between 50 and 65 years living in two areas of Flanders. Correlation between TEQ
      values of different groups of compounds were computed in these pool results and
      it was found that total toxic equivalencies (TEQs) correlated well with the
      values of the groups of contributing compounds: mono-ortho PCBs (r = 0.77), non
      ortho PCBs (r = 0.65) and PCDD/Fs (r = 0.88). The total TEQ was lower correlated
      to the CALUX-TEQ (r = 0.57). When calculating associations between those classes
      of compounds in the two studied regions separately, they were all higher
      correlated in the urban area compared to the more rural region. High correlation
      coefficients (r > 0.80) were also calculated between individual compounds and
      groups of compounds. It was suggested that in this studied background-exposed
      population, some compounds could be good predictors for a group: e.g. PCB 153 for
      indicator and total PCBs, PCB 118 for total PCB TEQ, PCB 156 for mono-ortho PCB
      TEQs and total TEQ, 2,3,4,7,8-P5CDF for PCDD/F TEQs and total TEQs. This means
      that in pooled serum samples correlations between persistent organochlorine
      compounds are as strong as for individual POP measurements observed in earlier
      studies.

PMID- 12222777
TI  - Comparison of dioxin and furan TEQ determination in contaminated soil using
      chemical, micro-EROD, and immunoassay analysis.
AB  - High resolution mass spectrometry gas chromatography (GC/MS) is the standard
      method for dioxin and furan analysis in environmental matrices. Considered as
      very accurate, this method is however time consuming and expensive. Methods based
      on biological interactions have the necessary sensitivity but began only recently
      to be investigated in the context of environmental applications. We have compared
      dioxin and furan toxicity levels (expressed as toxic equivalent quantities
      (TEQs)) in soil samples by three analytical approaches: the micro-ethoxyresorufin
      o-deethylase (EROD) bioassay (a receptor-based method), an immunoassay (antibody
      based method) and GC/MS analysis (used as a reference) using a shortened
      extraction-purification method. Both biological methods were sensitive to
      interferences from compounds co-extracted from samples. Most samples were
      underestimated by the immunoassay and, at a greater extent, overestimated by the
      EROD bioassay. The average accuracy of TEQ estimation (86 +/- 45% of values
      established by GC/MS) and the absence of false-negatives showed by the
      immunoassay suggest the usefulness of this method for semi-quantitative,
      preliminary characterization of potentially contaminated sites.

PMID- 12222778
TI  - Portal absorption of 14C after ingestion of spiked milk with 14C-phenanthrene,
      14C-benzo[a]pyrene or 14C-TCDD in growing pigs.
AB  - Polycyclic aromatic hydrocarbons (PAHs) and dioxins are lipophilic organic
      pollutants occurring widely in the terrestrial environment. In order to study the
      PAHs and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) transfer in the food chain,
      pigs have been fed with milk mixed either with 14C-phenanthrene, with 14C
      benzo[a]pyrene or with 14C-TCDD. The analysis of portal and arterial blood
      radioactivity showed that both PAHs and TCDD were absorbed with a maximum
      concentration at 4-6 h after milk ingestion. Then, the blood radioactivity
      decreased to reach background levels 24 h after milk ingestion. Furthermore, the
      portal and arterial blood radioactivities were higher for phenanthrene (even if
      the injected load was the lowest) than these of benzo[a]pyrene or these of TCDD,
      in agreement with their lipophilicity and water solubility difference. Main 14C
      absorption occurred during the 1-3 h time period after ingestion for 14C
      phenanthrene and during the 3-6 h time period for 14C-benzo[a]pyrene and for 14C
      TCDD. 14C portal absorption rate was high for 14C-phenanthrene (95%), it was
      close to 33% for 14C-benzo[a]pyrene and very low for 14C-TCDD (9%). These results
      indicate that the three studied molecules have a quite different behaviour during
      digestion and absorption. Phenanthrene is greatly absorbed and its absorption
      occurs via the blood system, whereas benzo[a]pyrene and TCDD are partly and
      weakly absorbed respectively. However these two molecules are mainly absorbed via
      the portal vein.

PMID- 12222779
TI  - A pilot and field investigation on mobility of PCDDs/PCDFs in landfill site with
      municipal solid waste incineration residue.
AB  - A field investigation by boring was carried out in a landfill site primarily with
      municipal solid waste incineration residue. From the collected core samples,
      vertical profiles of homologous content of polychlorinated dibenzo-p-dioxins and
      polychlorinated dibenzofurans (PCDDs/PCDFs) in the landfill layer were traced and
      the behavior of PCDDs/PCDFs was examined. In addition, a pilot-scale study was
      conducted on the PCDDs/PCDFs leached from incineration fly ash and the treated
      one using large landfill simulation columns (lysimeters) and the leaching
      behavior of PCDDs/PCDFs was examined. As a result, it was found that the
      coexistence of dissolved coloring constituents (DCCs), which might be composed of
      constituents like dissolved humic matters having strong affinity for hydrophobic
      organic pollutants, could enhance the leachability of PCDDs/PCDFs, thus
      contributing to the vertical movement and leaching behavior of PCDDs/PCDFs in the
      landfill layers of the incineration residue. Moreover, it is highly probable that
      DCCs derive from the unburned carbon in the bottom ash mixed and buried with the
      fly ash containing a high content of PCDDs/PCDFs.

PMID- 12222781
TI  - Inventory of marine biotest methods for the evaluation of dredged material and
      sediments.
AB  - An inventory of marine biotest methods for the evaluation of dredged material and
      sediments was compiled on behalf of the Federal Environmental Agency of Germany.
      Relevant assays were identified from the literature and experts from several
      countries contributed to a questionnaire survey on established and developing
      procedures. The biotest methods are applicable to whole sediment, sediment
      suspension, sediment elutriate, porewater and/or sediment extract. The endpoints
      cover acute and long-term toxicity, bioaccumulation, endocrine effects, toxic
      effects on reproduction, carcinogenicity and mutagenicity. Comparative analyses
      and evaluation of the biotest methods were conducted with regard to their
      sensitivity, specificity, applicability (regional specificity, availability and
      suitability of the test organisms), variability (physicochemical factors, natural
      factors and factors related to sampling and testing), cost-effectiveness, aspects
      of animal ethics, standardization (guidelines, intercalibration) and application
      for monitoring purposes in the areas of the OSPAR and Helsinki Conventions. The
      available information was integrated to rate the validity of the methods, their
      relevance for assessing impacts on ecosystems and the suitability of the methods
      for the evaluation of marine sediments and dredged material. Based on the rating
      of the individual bioassays, a tiered testing is suggested in a hierarchical
      approach representing a variety in taxa, biological processes and exposure
      routes, thereby covering the cellular, species, population and community level
      with a wide discriminatory and sensitivity range. The toxicological significance
      and complexity increases with the tiers: (1) screening and detection of impacts,
      (2) characterization of toxic effects, (3) verification of in situ alterations.

PMID- 12222780
TI  - Effect of copper chloride on the emissions of PCDD/Fs and PAHs from PVC
      combustion.
AB  - The influences of temperature, air flow and the amount of copper chloride upon
      the types and amount of the toxic emissions such as polychlorinated dibenzo-p
      dioxins and polychlorinated dibenzofurans (PCDD/Fs) and polycyclic aromatic
      hydrocarbons (PAHs) during combustion of polyvinyl chloride (PVC) were
      investigated. The mechanism concerning the effect of temperature and copper
      chloride on the PCDD/Fs and PAHs formation was discussed. The results shown that
      without copper chloride, trace amounts of PCDD/Fs and large amounts of PAHs were
      found in the emissions from the pure PVC combustion under various combustion
      conditions. The addition of copper chloride enhanced PCDD/Fs formation, but it
      seems that the formation of PAHs decreased with increasing amount of copper
      chloride, and greater total amount of PAHs were produced at the higher
      temperature under our experimental conditions.

PMID- 12222782
TI  - Assessment of human exposure to PCDDs, PCDFs and Co-PCBs using hair as a human
      pollution indicator sample I: Development of analytical method for human hair and
      evaluation for exposure assessment.
AB  - Dioxins including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated
      dibenzofurans (PCDFs) and co-planar polychlorinated biphenyls (Co-PCBs) are
      highly toxic. Even at environmental pollution levels, they cause hormonal damage
      in women, and they have been shown to induce immunosuppression and genital
      function damage in humans. In this study, a new method using isotope dilution was
      established to detect PCDDs, PCDFs and Co-PCBs in human hair. This method,
      comprised of washing and cutting of hair, alkaline decomposition, hexane
      extraction, multilayer silica gel column chromatography, high performance liquid
      chromatography with a porous graphite carbon column and analysis by high
      resolution gas chromatography/high resolution mass spectrometry, enabled us to
      analyze PCDDs, PCDFs and Co-PCBs at trace levels of less than pg/g with good
      reproducibility. In addition, there was a correlation between some isomers in
      human hair and blood collected from identical donors. Human hair analysis is
      useful to evaluate human risk assessment including that due to environmental
      pollution.

PMID- 12222783
TI  - Identification of dimethylchloroarsine near a former herbicide factory by
      headspace solid-phase microextraction gas chromatography-mass spectrometry.
AB  - The application of an improved method based on multidetector gas chromatography
      to the determination of trace levels of organoarsines in complex matrices is
      described. The method using headspace-mode solid-phase microextraction (SPME) was
      applied to a carefully sampled and preserved freshwater sediment core obtained
      from central Green Bay, Lake Michigan. The sediment core was collected and
      fractionated in an inert atmosphere. A carboxen/ polydimethylsiloxane-coated SPME
      fiber (85 microm film thickness) was equilibrated (n = 4) for 60 min at 25
      degrees C in the headspace of the sample vessel before introduction to the
      chromatograph. Conventional quadrupole ion trap mass spectrometry (electron
      impact ionization), electron capture detection, and pulsed flame photometric
      detection (arsenic mode) were employed for structure elucidation. A heretofore
      unidentified species in this region, dimethylchloroarsine (DMCA). was identified.
      The mass spectrum for DMCA is interpreted based on the observed fragmentation
      pattern. A bimodal vertical distribution of DMCA in the sediment core sample was
      observed and its interpretation based on Pb-210 dating is reported.

PMID- 12222784
TI  - Long-term tillage effects on soil metolachlor sorption and desorption behavior.
AB  - Sorption and desorption are two important processes that influence the amount of
      pesticides retained by soils. However, the detailed sorption mechanisms as
      influenced by soil tillage management are unclear. This study examined the
      sorption and desorption characteristics of metolachlor [2-chloro-N-(2-ethyl-6
      methyphenyl)-N-(2-methoxy-1-methylethyl)-acetamide] using the soil samples
      collected from the long-term conservation tillage (CnT) and conventional tillage
      (CT) research plots established in 1979 in Darlinton, SC. Humic acid (HA) and
      humin were extracted from the soils and used in the sorption experiments along
      with the whole soil samples. The sorption experiments were conducted using a
      batch-equilibration method. Three sequential desorption rinses were carried out
      following the sorption experiments. By comparing metolachlor sorption and
      desorption results we observed hysteresis for all soil samples and their organic
      matter fractions. Sorption nonlinearity (N) and hysteresis were dependent on the
      structure and composition of soil organic matter (SOM), e.g., Freundlich isotherm
      exponents (N) of HA and humin from CnT were higher than those of CT treatment,
      which may be related to high aromaticity of SOM fractions in CT treatment.
      Sorption capacity (K'f) was positively correlated with soil organic carbon (SOC)
      content. These results show that long-term tillage management can greatly affect
      metolachlor sorption and desorption behavior probably by qualitative differences
      in the structural characteristics of the humic substances.

PMID- 12222785
TI  - Soil temperature effect in calculating attenuation and retardation factors.
AB  - The effect of annual variation of daily average soil temperature, at different
      depths, in calculating pesticides ranking indexes retardation factor and
      attenuation factor is presented. The retardation factor and attenuation factor
      are two site-specific pesticide numbers, frequently used as screening indicator
      indexes for pesticide groundwater contamination potential. Generally, in the
      calculation of these two factors are not included the soil temperature effect on
      the parameters involved in its calculation. It is well known that the soil
      temperature affects the pesticide degradation rate, water-air partition
      coefficient and water-soil partition coefficient. These three parameters are
      components of the retardation factor and attenuation factor and contribute to
      determine the pesticide behavior in the environment. The Arrhenius equation,
      van't Hoff equation and Clausius-Clapeyron equation are used in this work for
      estimating the soil temperature effect on the pesticide degradation rate, water
      air partition coefficient and soil-water partition coefficient, respectively.
      These dependence relationships, between results of calculating attenuation and
      retardation factors and the soil temperature at different depths, can aid to
      understand the potential pesticide groundwater contamination on different weather
      conditions. Numerical results will be presented with pesticides atrazine and
      lindane in a soil profile with 20 degrees C constant temperature, minimum and
      maximum surface temperatures varying and spreading in the soil profile between -5
      and 30 degrees C and between 15 and 45 degrees C.

PMID- 12222786
TI  - The application of an open tubular trap in analysis of organic air pollutants.
AB  - The paper presents the studies on equilibrium trapping of organic air pollutants.
      A piece of a commercial capillary chromatographic column coated with
      polydimethylsiloxane was used for trapping. This kind of the trap was applied for
      sampling and enrichment of selected volatile nonpolar organic compounds from
      workplace atmosphere (woodworking shop). In the method developed, which is based
      on equilibrium trapping the concentration of analytes in a studied medium can be
      calculated from the partition coefficients determined in a calibration step and
      the amount of particular analytes trapped. Simultaneously with equilibrium
      trapping, analytes were sampled into sorbent packed tubes. The concentrations of
      analytes in woodworking shop atmosphere obtained with both sampling methods
      (equilibrium and dynamic) were in good agreement.

PMID- 12222787
TI  - Amorphous and condensed organic matter domains: the effect of persulfate
      oxidation on the composition of soil/sediment organic matter.
AB  - The composition of amorphous and condensed soil/sediment organic matter (SOM)
      domains was investigated for one soil sample and four sediment samples. These
      samples were oxidized with persulfate to remove amorphous SOM, before and after
      which the composition of SOM was studied by thermogravimetric analysis, pyrolysis
      GC/MS, and cross polarization magic angle spinning 13C-NMR. Comparison of the SOM
      composition before and after oxidation showed that condensed SOM was more
      thermostable and less polar than amorphous SOM. Condensed SOM was relatively low
      in O-alkyl C and carboxyl C and it was likely to contain only small amounts of
      labile organic components (carbohydrates, peptides, fatty acids). Apart from
      these general characteristics, the composition of the condensed and amorphous
      domains appeared to be highly dependent on the origin and nature of the SOM
      investigated. Condensed domains in relatively undecomposed SOM were enriched in
      aliphatic C, whereas condensed domains in relatively weathered SOM were enriched
      in aromatic C. Altogether, the compositional changes upon persulfate oxidation
      were similar to the compositional changes upon humification, which supports the
      idea that weathered SOM is more condensed than the original material.

PMID- 12222788
TI  - Qualitative evaluation of the mineralogical and chemical composition of dry
      deposition in the central and southern highlands of Jordan.
AB  - The chemical and mineralogical composition of dry deposition in the western
      highlands of central and south Jordan at the end of the summer season 2000,
      reflect the composition of soils in addition to anthropogenic activities at these
      areas. Calcite predominated in the central region whereas calcite and quartz are
      the dominant minerals in south Jordan. The concentrations of Hg, Cr, Ni, Cu, Pb
      and Zn were higher in central Jordan, which might be attributed to higher
      anthropogenic activities than south. On the other hand, Fe, Mn, Ti, Ba, Sr, Y and
      Rb were higher in the south of Jordan reflecting the composition of soil at these
      sites. At Aqaba city, the only port of Jordan, where Cr, Cd, As and S were higher
      than other areas. This variation might be attributed to the contribution of
      phosphate dust in the atmosphere through handling processes.

PMID- 12222789
TI  - Study of chlorothalonil photodegradation in natural waters and in the presence of
      humic substances.
AB  - Photodegradation of chlorothalonil was studied in different natural waters (sea,
      river and lake) as well as in distilled water under natural and simulated solar
      irradiation. The effect of dissolved organic matter (DOM) such as humic and
      fulvic substances on the photodegradation rate of chlorothalonil was also studied
      in simulated sunlight. The presence of DOM enhanced the photodegradation of
      chlorothalonil with the exception of seawater. The kinetics were determined
      through gas chromatography electron capture detection (GC/ECD) and the
      photodegradation proceeds via pseudo-first-order reaction in all cases. Half-life
      ranged from 1 to 48 h. In natural and humic water chlorothalonil photodegradation
      gave rise to two different intermediates compared to distilled water
      demonstrating that the transformation of chlorothalonil depend on the
      constitution of the irradiated media and especially from DOM. The byproducts
      identified by GC/MS techniques were: chloro-1,3-dicyanobenzene, dichloro-1,3
      dicyanobenzene, trichloro-1,3-dicyanobenzene and benzamide.

PMID- 12222790
TI  - Burial, exportation and degradation of acyclic petroleum hydrocarbons following a
      simulated oil spill in bioturbated Mediterranean coastal sediments.
AB  - A field study was conducted in a French Mediterranean littoral (Gulf of Fos) in
      order to determine the role of bioturbation processes during the bioremediation
      of oil-contaminated sediments. Inert particulate tracers (luminophores) and
      Arabian light crude oil were deposited at the surface of sediment cores incubated
      in situ for 2, 6 and 12 months. After incubation, luminophores and hydrocarbons
      presented roughly similar depth distributions in the sediment, showing a
      continuous burial of material until 55 mm depth. Short-chain (< or = n-C25) n
      alkanes were totally removed from the sedimentary column after 6 months, whereas
      approximately 20% of heavier n-alkanes (e.g. n-C30) and of isoprenoid
      hydrocarbons (pristane (Pr) and phytane (Ph)) remained at the end of the
      experiment. The determination of the degradation constant and the turn-over rate
      of individual hydrocarbon indicated that C17-25 n-alkanes were degraded two to
      three times faster than longer homologues and than pristane and phytane. Using
      the 17alpha,21beta-C30-hopane as an internal inert reference, we could
      demonstrate that, after 12 months of in situ incubation, 55% of the losses of the
      n-alkanes < or = C25 and 35% of the losses of the heavier n-alkanes and of Pr and
      Ph were due to biodegradation processes. These results demonstrate that the
      activity of benthic organisms can have a significant influence on the qualitative
      and quantitative fate of acyclic hydrocarbons following a petroleum contamination
      in marine coastal sediments.

PMID- 12222791
TI  - Humic acid complexation of basic and neutral polycyclic aromatic compounds.
AB  - Complexation by humic acid (HA) of basic (quinoline) and neutral (naphthalene)
      polycyclic aromatic compounds (PACs) was compared using fluorescence spectroscopy
      and equilibrium dialysis (ED). These compounds sorb to HA via cation exchange and
      hydrophobic interactions, respectively. Ionization of quinoline strongly affects
      its sorption to HA; maximum sorption is observed at pH close to logKb (4.92), and
      competition with H+ and electrolyte cation (Li+) is evident. Spectroscopic
      experiments indicate that quinolinium (QH+) cation fluorescence is quenched via a
      static mechanism (i.e., a dark complex is formed) when the protonated form is
      adsorbed via ion exchange to HA. The extent of sorption, calculated from
      fluorescence data using the Stern-Volmer equation, was compared to independent ED
      measurements. Although both methods indicated the same trends with solution
      chemistry, fluorescence quenching data suggested more extensive complexation than
      that measured using ED. In contrast to ionizable PACs, studied here and
      previously, interaction of naphthalene with HA is unaffected by changes in
      solution conditions (pH, ionic strength).

PMID- 12222792
TI  - Herbicide safeners: uses, limitations, metabolism, and mechanisms of action.
AB  - Several methods were examined to minimize crops injury caused by herbicides. Thus
      increase their selectivity. A selective herbicide is one that controls weeds at
      rates that do not injure the crop. Herbicides are selective in a particular crop
      within certain limits imposed by the herbicide, the plant, the application rate,
      the method and time of application, and environment conditions. Herbicide
      safeners are compounds of diverse chemical families. They are applied with
      herbicides to protect crops against their injury. Using chemical safeners offer
      practical, efficient and simple method of improving herbicide selectivity. This
      method has been applied successfully in cereal crops such as maize, rice and
      sorghum, against pre-emergence thiocarbamate and chloroacetanilide herbicides.
      Some reports indicate promising results for the development of safeners for post
      emergence herbicides in broadleaved crops. Various hypotheses were proposed
      explaining mechanisms of action of herbicide safeners: interference with uptake
      and translocation of the herbicide, alteration in herbicide metabolism, and
      competition at site of action of the herbicide. Even though progress was made in
      the development of herbicide safeners and in understanding their mechanisms of
      action, more research is needed to elucidate clearly how these chemicals act and
      why their activity is restricted to particular crops and herbicides.

PMID- 12222793
TI  - Volatile organic compounds from leaves litter.
AB  - Qualitative composition of volatile emissions of litter of five species of
      deciduous trees was investigated by GC-MS. The list of identified substances
      contains more than 70 organic compounds of various classes. It was established
      that the composition of components emitted by the litter into the gas phase
      greatly differs from that of essential oils extracted by hydrodistillation from
      turned leaves collected from trees during fall. It is suggested that most
      compounds found in litter emissions are products of vital activity of
      microorganisms decomposing it. The reported data indicate that after the
      vegetative period is over the decomposition processes of litter are important
      seasonal sources of reactive organic compounds under the forest canopy.

PMID- 12222794
TI  - Levels and pattern of volatile organic nitrates and halocarbons in the air at
      Neumayer Station (70 degrees S), Antarctic.
AB  - Levels and patterns of C1-C4/C9 organic nitrates were measured for the first time
      in Antarctica. The sampling was done by adsorptive enrichment on Tenax TA
      followed by thermodesorption cold-trap high resolution capillary gas
      chromatography with electron capture detection. 2-70 1 air on-column have been
      analyzed this way. C1-C9 alkyl mononitrates, C2-C4 alkyl dinitrates, C2-C4
      hydroxy alkyl nitrates, and halocarbons could be identified in air samples
      collected near the German Neumayer Research Station, Antarctica, in February
      1999. Volatile biogenic and anthropogenic halocarbons were used to assess the
      origin of the air parcels analyzed. The average concentration measured for
      sigmaC2-C6 alkyl nitrates was in the range of 9.2 +/- 1.8 ppt(v), while the sum
      of the mixing ratios of six C2-C4 hydroxy alkyl nitrates was in the range of 1.1
      +/- 0.2 ppt(v). Moreover, C2-C4 alkyl dinitrates were found at levels near the
      detection limit of 0.1-0.5 ppt(v). The concentrations of organic nitrates found
      in Antarctic air represent ultimate baseline levels due to chemical and physical
      loss processes during long-range transport in the air. The South Atlantic and the
      Antarctic Ocean as a general secondary source for organic nitrates in terms of an
      air/sea exchange equilibrium has to be evaluated yet, but it seems logical. Our
      results confirm the common assumption that there are no biogenic marine sources
      of C2-C9 organonitrates. We have found a level of > 80 ppt(v) for methyl nitrate.
      This level if it can be confirmed in a systematic survey requires a strong
      biogenic source of methyl nitrate in the Antarctic Ocean.

PMID- 12222795
TI  - Comparative study of extraction methods for the determination of PAHs from
      contaminated soils and sediments.
AB  - The following four methods were compared on the extraction efficiency of 16 EPA
      (US Environmental Protection Agency) polycyclic aromatic hydrocarbons (PAHs):
      German method of the Verband Deutscher Landwirtschaftlicher Untersuchungs und
      Forschungsanstalten (VDLUFA), two methods of the International Organization for
      Standardization using shaking (ISO A) and Soxhlet extraction (ISO B) and an
      ultrasonic method. Recovery rates of 16 PAHs were determined in two soils.
      Extraction efficiency was evaluated in five soils and three sediments. Effect of
      drying soils and sediments on extraction efficiency was tested using the VDLUFA
      and the ultrasonic methods. Our study shows that the number of aromatic rings,
      rather than extraction procedures, significantly influenced recovery rates of
      individual PAHs. No significant differences in extraction efficiency of the four
      methods were observed for less polluted samples. For highly polluted soils,
      extraction efficiency decreased in the following order: VDLUFA method > ISO A >
      ultrasonic method > ISO B. Influence of soil moisture on extraction efficiency
      depended to some extent on both solvent used and content of PAHs in samples. A
      mixture of dichloromethane/acetone (5:1) is recommended for PAH extraction from
      moist samples when the ultrasonic method is used.

PMID- 12222796
TI  - Feeding standards for lactating riverine buffaloes in tropical conditions.
AB  - Data from 33 feeding trials, conducted on lactating riverine buffaloes from
      different institutes across India, were subjected to multiple regression analysis
      to derive nutritional requirements for dry matter (DM), total digestible
      nutrients (TDN), crude protein (CP) and digestible crude protein (DCP) for
      maintenance, milk production and body weight gain. Maintenance requirements for
      DM, TDN, CP and DCP were 59.9, 35.3, 5.43 and 3.14 g/kgW(0.75), respectively;
      corresponding requirements for producing 1 kg 6% FCM were 688, 406, 90.3 and 55.2
      g and for 1 g gain in body weight were 3.37, 1.97, 0.327 and 0.23 g. Regression
      equations had high R2 values (061. 0.66, 0.84 and 0.68 for prediction of DM, TDN,
      CP and DCP, respectively) and the equations (F-value) as well as coefficients
      were highly significant (P <0.001). Regressed values were used to derive feeding
      standards. Derived values matched well with the actual intake versus performance
      of animals under diverse feeding conditions. New standards predicted requirements
      and intake of nutrients for different production levels better than existing
      feeding standards. Because they are based on a more thorough analysis of data,
      the new feeding standards will be appropriate for use widely in India.

PMID- 12222797
TI  - Fatty acid composition of ewe milk as affected by solar radiation and high
      ambient temperature.
AB  - Forty lactating Comisana ewes were either exposed to or protected from solar
      radiation and fed either in the morning or afternoon during summer in a
      Mediterranean climate. Individual milk samples were taken on days 7, 21 and 42 of
      the study period to determine fatty acid composition by gas chromatography.
      Exposure to solar radiation resulted in higher proportions of short-chain and
      saturated fatty acids in milk, primarily because of increased contents of
      caproic, capric, lauric, myristic and stearic acids (by 3-18%), and decreased
      contents of oleic, linoleic and linolenic acids (by 2-9%). As a consequence, the
      long to short chain and the unsaturated to saturated fatty acid ratios were
      significantly higher by 4 and 13% respectively in the milk of the protected ewes
      compared with that of the exposed animals. Provision of shade also led to an
      increase in the 18:0+18:1 to 16:0 ratio, and to a decrease in the 12:0 + 14:0 +
      16:0 fatty acid group, which are regarded as reliable indexes of the nutritional
      property of dietary fat in reducing cholesterol levels in human plasma. Feeding
      time had little impact on milk fat. Our findings suggest that high ambient
      temperature may markedly modify the lipid composition of ewe milk and that
      provision of shade, but not feeding management, can improve the milk fatty acid
      profile in dairy sheep raised in hot climates.

PMID- 12222798
TI  - Expression of urokinase plasminogen activator receptor in resting and activated
      bovine neutrophils.
AB  - Changes in urokinase-plasminogen activator (u-PA) and u-PA receptor (u-PAR)
      expression at the protein and mRNA level in resting neutrophils and in
      neutrophils activated by phorbol myristate acetate (PMA) were examined. Low
      amounts of u-PA were found intracellularly or membrane-bound in resting
      neutrophils. However, incubation of resting neutrophils with purified exogenous u
      PA (10 IU/ml) revealed extensive binding of u-PA to cell membranes. Excess amino
      terminal fragment of the u-PA molecule, a proteolytically inactive fragment of u
      PA (amino acids 1-135) blocked binding of exogenous u-PA to the cell membrane.
      These results, collectively, indicate that the binding of u-PA is specific and
      that resting neutrophils have unoccupied u-PA receptors on their cell membrane.
      Addition of PMA led to an increase (P < 0.01) in total cell-associated, membrane
      bound u-PA activity and u-PA mRNA expression by bovine neutrophils. In contrast.
      PMA increased u-PAR mRNA levels but this was accompanied by a decrease (2.5-fold;
      P < 0.01) in free, unoccupied u-PA binding sites. No significant effects on total
      cell-associated or membrane-bound u-PA were found when neutrophils were treated
      with 4-phorbol 12,13 didecanoate, a phorbol ester that does not activate protein
      kinase C (PKC). Furthermore, addition of 1-(5-isoquinolinesylphonyl)-2
      methlylpiperazine dihydrochloride (H-7), a potent PKC inhibitor, blocked the
      effect of PMA on total cell-associated u-PA activity. Thus, PKC plays a role in
      the modulation of u-PA and u-PAR by PMA in bovine neutrophils.

PMID- 12222799
TI  - Eukaryotic elongation factor-2 (eEF-2) activity in bovine mammary tissue in
      relation to milk protein synthesis.
AB  - The amount of protein synthesis translational elongation factor 2 (eEF-2) was
      estimated employing diphtheria toxin-dependent ADP-ribosylation in samples
      prepared from small amounts of tissue from mammary gland, skeletal muscle and
      liver from lactating dairy cows. A very high level of ADP-ribosylatable eEF-2 was
      found in mammary gland, amounting to 20-times the level found in liver and 50
      times the level found in skeletal muscle. This obviously reflects the high
      protein synthesis activity in mammary tissue. To our knowledge, similar high
      activities have previously been reported only for cancer cells. A close linear
      relationship was found between the amount of diphtheria-toxin catalysted ADP
      ribosylated eEF-2 and protein and casein output in milk from cows in late
      lactation. This strongly suggests that eEF-2 may be a limiting factor in milk
      protein synthesis.

PMID- 12222800
TI  - Microbial composition, including the incidence of pathogens, of goat milk from
      the bergamo region of italy during a lactation year.
AB  - Sixty samples of raw goat milk intended for Caprino cheese-making were collected
      from ten farms in the Bergamo area over a 6-month period. Analyses of main
      microbial groups, somatic cell count (SCC) and pH were performed to determine the
      effect of origin (farm) and lactation period (April - September) on microbial
      composition and the incidence of pathogens in milk. Overall mean values were:
      standard plate count (SPC), 5.0 x 10(4) cfu/ml; yeasts, 2.5 x 10(2) cfu/ml;
      coliforms, 91 x 10(2) cfu/ml; Escherichia coli, 2.9 cells/ml: enterococci, 1.1 x
      10(2) cfu/ ml; lactococci, 3 4 x 10(3) cfu/ml; lactobacilli, 3.0 x 10(3) cfu/ml;
      halotolerant bacteria, 8.2 x 10(3) cfu/ml; spores of mesophilic aerobic bacteria,
      11 cfu/ml; SSC, 9.9 x 10(5) cells/ml; pH, 6.63. Moulds and spores of sulphite
      reducing clostridia were found intermittently. Neither Salmonella spp. nor
      Listeria monocytogenes was detected, while Esch. coli O157: H7 was isolated from
      one milk sample (an incidence of 1.7%). Staphylococcus aureus was discovered at a
      level > 10(2) cfu/ml in 26 samples (43%) with an overall mean of 12 x 10(3)
      cfu/ml, whereas coagulase-negative staphylococci were found in 54 samples (90%)
      with an overall mean of 1.3 x 10(3) cfu/ml. Of Staph. aureus strains, 23% proved
      to be enterotoxinogenic with a prevalence of enterotoxin C producers. Staph.
      caprae was the coagulase-negative species most frequently isolated; none of the
      coagulase-negative staphylococci strains synthesized any of the enterotoxins
      tested for. Sample source was the major factor affecting the microbial
      composition of goat milk: significant differences (P < 0.01) were observed among
      samples from different farms for SPC, coliforms, lactococci, lactobacilli and
      halotolerant bacteria. Period of lactation had a significant effect (P < 0.025)
      on SCC and pH. SPC correlated well with coliforms, lactococci and lactobacilli;
      SSC did not reveal positive interactions with any microbial groups or pH.

PMID- 12222801
TI  - Spoilage patterns of skim and whole milks.
AB  - The reason for the reported difference in spoilage behaviour of skim and whole
      pasteurised milks was investigated. The rates of growth of psychrotrophic
      bacteria were not significantly different in the two milks and the bacterial
      types, all pseudomonads, present at spoilage were also similar. However, when
      representative spoilage organisms were cultured into freshly pasteurised skim and
      whole milks, skim milks exhibited predominantly bitter flavours while whole milk
      showed mostly sour flavours. The different spoilage behaviours can be largely
      explained by greater proteolvsis in skim milk than in whole milk, caused by
      higher production of protease and greater susceptibility of the protein to
      protease attack. In addition, lipolysis in whole milk, caused by the substantial
      quantities of lipase produced by spoilage pseudomonads in this milk, also
      contributes to the different flavours produced during cold storage of these milk
      types.

PMID- 12222802
TI  - Manothermosonication of heat-resistant lipase and protease from Pseudomonas
      fluorescens: effect of pH and sonication parameters.
AB  - The effect of different parameters (pH, ultrasonic amplitude and pressure) on the
      resistance to heat and manothermosonication (MTS) treatments of heat resistant
      lipase and protease produced by Pseudomonas fluorescens B52 and NCDO 2085,
      respectively, were studied. Lipase B52 thermoresistance decreases with an
      increase of pH. However, inactivation by MTS seems to be pH independent. There
      were only slight increases in the MTS efficiency when increasing pressure at UHT
      temperatures and the effect of amplitude was different depending on treatment
      temperature. Protease NCDO 2085, which was very resistant to MTS at 30 degrees C.
      was very sensitive to MTS at 76 degrees C. Increases in applied pressure had no
      effect on MTS efficiency at 140 degrees C and its inactivation by MTS was almost
      temperature independent between 76-109 degrees C. Data obtained are compared with
      previous published data and inactivation mechanisms are discussed.

PMID- 12222803
TI  - Lactobacillus reuteri DSM 20016: purification and characterization of a
      cystathionine gamma-lyase and use as adjunct starter in cheesemaking.
AB  - A homo-tetrameric approximately 160-kDa cystathionine gamma-lyase was purified to
      homogeneity from Lactobacillus reuteri DSM 20016 by four chromatographic steps.
      The activity was pyridoxal-5'-phosphate dependent and the enzyme catalyzed the
      alpha,gamma-elimination reaction of L-cystathionine, producing L-cysteine,
      ammonia and alpha-ketobutyrate. The enzyme was active towards a range of amino
      acids and amino acid derivatives, including methionine. The pH and temperature
      optima were found to be 8.0 and 35 degrees C. respectively. Isoelectric pH (pI)
      was approximately 5.0 as determined by two-dimensional electrophoresis.
      Sensitivity to chemical inhibitors was typical of lactococcal cystathionine gamma
      and beta-lyases, except it was inhibited by sulphydryl reagents. The N-terminal
      sequence was MKFNTQLIHGGNSED, which had 100% homology with cystathionine beta
      lyase of Lb. reuteri 104R (Accession Number (CAC05298). Lb. reuteri DSM 20016.
      together with 10 other strains of non-starter lactic acid bacteria, was used as
      adjunct starter in the production of miniature ('anestrato Pugliese-like cheeses.
      After 40 d ripening, the water-soluble extract of the cheeses with added
      Lactobacillus fermentum DT41 and Lb. reuteri DSM 20016 contained the highest
      enzyme activities on cystathionine and methionine substrates. Determinations of
      methanethiol, dimethyl sulphide, dimethyl disulphide and dimethyl trisulphide in
      the miniature cheeses confirmed the findings of enzyme activities.

PMID- 12222804
TI  - Thermal inactivation of chymosin during cheese manufacture.
AB  - The aspartic proteinase, chymosin (EC 3.4.23.4) is the principal milk clotting
      enzyme used in cheese production and is one of the principal proteolytic agents
      involved in cheese ripening. Varietal differences in chymosin activity, due to
      factors such as cheese cooking temperature, fundamentally influence cheese
      characteristics. Furthermore, much chymosin is lost in whey, and further
      processing of this by-product may require efficient inactivation of this enzyme,
      with minimal effects on whey proteins. In the first part of this study, the
      thermal inactivation kinetics of Maxiren 15 (a recombinant chymosin preparation)
      were studied in skim milk ultrafiltration permeate, whole milk whey and skim milk
      whey. Inactivation of chymosin in these systems (at pH 6.64) followed first order
      kinetics with a D45.5 value of 100 +/- 21 min and a z-value of 5.9 +/- 0.3
      degrees C. D-Values increased linearly with decreasing pH from 6.64 to 6.2, while
      z-values decreased as pH decreased from 6.64 to 6.4, but were similar at pH 6.4
      and 6.2. Subsequent determination of chymosin activity during manufacture of
      Cheddar and Swiss-type cheese showed good correlations between predicted and
      experimental values for thermal inactivation of chymosin in whey. However, both
      types of cheese curd exhibited relatively constant residual chymosin activity
      throughout manufacture, despite the higher cooking temperature applied in the
      manufacture of Swiss cheese. Electrophoretic analysis of slurries made from
      Cheddar and Swiss cheese indicated decreased proteolysis due to chymosin activity
      during storage of the Swiss cheese slurry, but hydrolysis of sodium caseinate by
      coagulant extracted from both cheese types indicated similar levels of residual
      chymosin activity. This may suggest that some form of conformational change other
      than irreversible thermal denaturation of chymisin takes place in cheese curd
      during cooking, or that some other physico-chemical difference between Swiss and
      Cheddar cheese controls the activity of chymosin during ripening.

PMID- 12222805
TI  - Influence of selected factors on browning of Camembert cheese.
AB  - Experimental Camembert cheeses were made to investigate the effects on browning
      of the following factors: inoculation with Yarrowia lipolytica, the use of
      Penicillium candidum strains with different proteolytic activity, the addition of
      tyrosine, and the addition of Mn2+ thus leading to 16 different variants of
      cheese. Two physical colour parameters were used to describe browning, depending
      on the location in the cheeses: a whiteness index for the outside browning (mould
      mycelium), and a brownness index for the inside browning (surface of the cheese
      body). Mn2+ promoted a significant increase of browning at both locations,
      whereas Yar. lipolytica had the opposite effect. Outside browning was
      significantly more intense when using the Pen. candidum strain with higher
      proteolytic activity. A significant interaction was found between Yar. lipolytica
      and Pen. candidum. The yeast had no effect in combination with a low proteolytic
      strain of Pen. candidum, but significantly reduced proteolysis and browning in
      combination with a high proteolytic strain of Pen. candidum. We further confirmed
      that both strains of Pen. candidum were able to produce brown pigments from
      tyrosine and thus both are presumably responsible for the browning activity in
      this type of cheese.

PMID- 12222806
TI  - Effect of bile components on the surface properties of bifidobacteria.
AB  - The action of bile on bifidobacteria was studied by measuring changes in zeta
      potential. hydrophobicity and adherence to enterocyte-like cells in vitro. Highly
      hydrophobic strains shocked with bile displayed more negative zeta potential
      values and a decrease in adherence. When a non-hydrophobic non-adherent strain
      (CIDCA 5324) was shocked with bile, an increase in hydrophobicity was observed.
      However, no changes of zeta potential or adherence properties were apparent. The
      action of the bile components was different from the action of whole bile.
      Cholate and deoxycholate produced a decrease in the negativity of zeta potential
      values of all strains studied whereas taurocholate displayed a shift in zeta
      potential of hydrophobic strains to more negative values, thus explaining the
      decrease in the autoaggregation by charge repulsion. However, the decrease in
      zeta potential caused by cholate and deoxycholate did not increase
      autoaggregation in a hydrophobic non-adherent strain (CIDCA 531). This suggests
      that other forces are contributing to autoaggregation.

PMID- 12222807
TI  - Immunological effects of yogurt addition to a re-nutrition diet in a malnutrition
      experimental model.
AB  - The therapeutic and preventive effects of yogurt and lactic acid bacteria on
      diseases such as cancer, infection and gastrointestinal disorders are well
      ocumented. The aim of this research was to study the effects of different doses
      of yogurt addition after milk re-nutrition diet, on the recovery of the
      intestinal barrier and mucosal immune function. Experiments were performed on
      groups of mice, malnourished and re-nourished with milk during 7 d, and mice with
      diet supplemented with yogurt for 2, 5 and 7 consecutive d. Nutritional
      parameters such as weight gain, serum total protein, and the number of IgA, IgM
      and IgG B cells of the small intestine were determined. We also quantified
      intraepithelial leukocytes, mastocytes and goblet cells, and performed structural
      and ultrastructural studies on the small intestine. We observed that 5 d of
      yogurt feeding was the optimal dose for improving gut barrier function and
      mucosal immune system in a malnutrition model. This effect was not observed with
      milk re-nutrition. Although the results were better for 5 d of yogurt, addition
      for 7 d also showed beneficial effects. Yogurt feeding in our model did not
      impair any gut functions. These results suggest that yogurt addition after a re
      nutrition diet gives better recovery of intestinal function than the re-nutrition
      diet usually recommended. Although these results were obtained in an animal
      model, they indicate that consumption of yogurt by malnourished children might
      accelerate the restoration of gut function.

PMID- 12222808
TI  - Effect of monensin sodium on lactational performance of autumn- and spring
      calving cows.

PMID- 12222809
TI  - Effect of intramammary infection by Staphylococcus caprae on somatic cell counts
      and milk composition in goats.

PMID- 12222810
TI  - Cytotoxic and antibacterial activities of chemically synthesized kappa-casecidin
      and its partial peptide fragments.

PMID- 12222811
TI  - Antimutagenic activities of various lactic acid bacteria against food mutagens:
      heterocyclic amines.

PMID- 12222812
TI  - Quantitative neuroanatomy and neuroinformatics.

PMID- 12222813
TI  - Neuroanatomical algorithms for dendritic modelling.
AB  - The complexity and variability of dendritic morphology constitutes a fascinating
      challenge to the investigation of the structure-activity-function relationship in
      the nervous system. Computational modelling has recently emerged as a powerful
      approach for the quantitative anatomical characterization of dendrites. The key
      idea is to design a stochastic algorithm to generate digital structures that are
      statistically indistinguishable from those of real neurons of a given
      morphological class. The set of parameters used by this algorithm would then
      constitute a complete and accurate description of that morphological class. We
      review the strengths and weaknesses of the major types of algorithms used to
      model dendrogram properties, including those based on branch diameter and on
      distance from the soma. We also describe some approaches to the simulation of
      dendritic orientation and three-dimensional geometry. Finally, we discuss the
      environmental influences on dendritic morphology (especially the presence of
      axons, other neurons, and anatomical boundaries) and thus the need to include
      models of the tissue volume in the algorithmic description of dendrites.

PMID- 12222814
TI  - Branching rates and growth functions in the outgrowth of dendritic branching
      patterns.
AB  - The outgrowth of dendritic branching patterns proceeds by neurite elongation and
      branching. These actions are supported by growth cones, specialized dynamic
      structures at the tips of outgrowing neurites, in response to a multitude of
      intracellular and extracellular signals and mechanisms. Branching rates of growth
      cones and their temporal patterns thus reflect the extent and changes in these
      responses. The present study outlines a model framework to relate branching rates
      of individual growth cones with the growth rate of the entire dendritic tree. The
      branching rate of an individual growth cone is assumed to depend on the total
      number of growth cones at any given moment (representing competition between
      growth cones), on its position along the dendrite, and on a baseline component
      representing all other factors. Four different strategies are discussed for
      determining quantitatively these components from experimental data. The methods
      are applied in the analysis of dendritic trees of Wistar rat multipolar non
      pyramidal neurons, quantitatively reconstructed at several developmental stages
      (Parnavelas J G and Uylings H B M 1980 Brain Res. 193 373-82, Uylings H B M,
      Parnavelas J G, Walg H and Veltman W A M 1980 Mikroskopie 37 220-4). It is shown
      that the baseline branching rate is a rapidly decreasing function of time,
      indicating the largest baseline drive for branching in the early days of
      outgrowth.

PMID- 12222815
TI  - A shape analysis framework for neuromorphometry.
AB  - This paper addresses in an integrated and systematic fashion the relatively
      overlooked but increasingly important issue of measuring and characterizing the
      geometrical properties of nerve cells and structures, an area often called
      neuromorphology. After discussing the main motivation for such an endeavour, a
      comprehensive mathematical framework for characterizing neural shapes, capable of
      expressing variations over time, is presented and used to underline the main
      issues in neuromorphology. Three particularly powerful and versatile families of
      neuromorphological approaches, including differential measures, symmetry
      axes/skeletons, and complexity, are presented and their respective potentials for
      applications in neuroscience are identified. Examples of applications of such
      measures are provided based on experimental investigations related to automated
      dendrogram extraction, mental retardation characterization, and axon growth
      analysis.

PMID- 12222816
TI  - The effect of dendritic topology on firing patterns in model neurons.
AB  - Neuronal firing patterns are influenced by both membrane properties and dendritic
      morphology. Distinguishing two sources of morphological variability-metrics and
      topology-we investigate the extent to which model neurons that have the same
      metrical and membrane properties can still produce different firing patterns as a
      result of differences in dendritic topology. Within a set of dendritic trees that
      have the same number of terminal segments and the same total dendritic length, we
      show that firing frequency strongly correlates with topology as expressed by the
      mean dendritic path length. The effect of dendritic topology on firing frequency
      is bigger for trees with equal segment diameters than for trees whose segment
      diameters obey Rall's 3/2 power law. If active dendritic channels are present,
      dendritic topology influences not only firing frequency but also type of firing
      (regular, bursting).

PMID- 12222817
TI  - Tracing tools to resolve neural circuits.
AB  - In this paper we summarize neuroanatomical tracing methods, in particular
      combinations of methods designed to achieve the combined goals of tracing
      connectivity and extracting extra information from the projection or the target
      neurons. These combinations include techniques that identify projection fibres
      together with the neurons from which they originate, methods which establish the
      morphological or chemical identity of the target neurons and techniques to verify
      the presence of contacts between the terminal boutons on fibres and prospective
      target neurons. In the second part of this paper we describe a method recently
      developed in our laboratory, which consists of fluorescence tracing (introducing
      marker #1) combined with immunofluorescence with different fluorochromes (markers
      #2 and #3). This method enables us to observe the distribution of terminals of a
      particular set of projection fibres in contact with neurons belonging to two
      chemically different populations of interneuron. Multifluorescence confocal laser
      scanning is used for image acquisition of fibres and processes of presumed target
      neurons, and follow-up is by three-dimensional computer reconstruction. These
      reconstructions are used to determine that the contacts between the
      differentially labelled structures are real, i.e. with no optically empty space
      in between regardless of the angle of inspection. The specific experiments
      reported in this paper comprise the tracing with biotinylated dextran amine of
      fibres in the rat brain running from the presubiculum to layer III of the medial
      division of the entorhinal cortex. We studied the possibility of contacts in the
      latter area between the terminal boutons of these projecting fibres in
      association with presumed target neurons, i.e. parvalbumin and calretinin
      expressing interneurons.

PMID- 12222818
TI  - Comparison of semi-automatic and automatic data acquisition methods for studying
      three-dimensional distributions of large neuronal populations and axonal
      plexuses.
AB  - Neuroanatomy is in need of high throughput methods for reliably recording the
      distribution of tissue elements across large brain regions. We compared two
      methods for recording the spatial distribution of identified neuronal elements
      such as tracer labelled cell bodies or axonal plexuses. The methods compared were
      computerized image-combining microscopy (semi-automatic method), which is a user
      controlled method providing feedback during digitization, and digital camera
      technology with image analysis software (automatic method). Both methods were
      applied to biotinylated dextran amine labelled axonal plexuses and FluoroRuby
      labelled neuronal cell bodies, in the pontine nuclei of the rat. Coordinates were
      assigned to the labelled elements using both methods. The ensuing distribution
      patterns were compared, section by section, and in three-dimensional
      reconstruction. The experienced investigator, using the semi-automatic method,
      could detect individual axons, fragments of axons, weakly labelled elements, and
      overlapping cell bodies, better than the automatic system. Nevertheless, both
      methods detected the overall distribution of the labelled axons and cells
      investigated. Automatic methods provide opportunities for efficient large-scale
      data acquisition of labelled neuronal elements.

PMID- 12222819
TI  - Neuronal morphology data bases: morphological noise and assesment of data
      quality.
AB  - For technical, instrumental and operator-related reasons, three-dimensional
      reconstructions of neurons obtained from intracellularly stained neuronal pieces
      scattered in serial sections are blurred by some morphological noise. This noise
      may strongly invalidate conclusions drawn from models built using the three
      dimensional reconstructions and it must be taken into account when retrieving
      digitized neurons from available databases. We analyse the main generating
      sources of the noise and its consequences for the 'quality' of the data. We
      provide tools for detecting and evaluating the noise in any database providing
      sufficient information is given in the database. We propose a unified format for
      submitting data and a new neuron viewer/editor to analyse the digitized neurons
      with our tools.

PMID- 12222820
TI  - Analysis of tubular structures in three-dimensional confocal images.
AB  - Knowledge about the relationship between morphology and the function of neurons
      is an important instrument in understanding the role that neurons play in
      information processing in the brain. In paricular, the diameter and length of
      segments in dendritic arborization are considered to be crucial morphological
      features. Consequently, accurate detection of morphological features such as
      centre line position and diameter is a prerequisite to establish this
      relationship. Accurate detection of neuron morphology from confocal microscope
      images is hampered by the low signal to noise ratio of the images and the
      properties of the microscope point spread function (PSF). The size and the
      anisotropy of the PSF causes feature detection to be biased and orientation
      dependent. We deal with these problems by utilizing Gaussian image derivatives
      for feature detection. Gaussian kernels provide for image derivative estimates
      with low noise sensitivity. Features of interest such as centre line positions
      and diameter in a tubular neuronal segment of a dendritic tree can be detected by
      calculating and subsequently utilizing Gaussian image derivatives. For diameter
      measurement the microscope PSF is incorporated into the derivative calculation.
      Results on real and simulated confocal images reveal that centre line position
      and diameter can be estimated accurately and are bias free even under realistic
      imaging conditions.

PMID- 12222821
TI  - Measures for quantifying dendritic arborizations.
AB  - Topological and metrical measures are reviewed, which describe whole dendritic
      trees and variables within trees. These measures are applied to differentiate and
      classify groups of neurons. They are also of importance for simulation or
      reconstruction of neuronal trees in view of functional computational
      characteristics.

PMID- 12222822
TI  - Non-curated distributed databases for experimental data and models in
      neuroscience.
AB  - Neuroscience is generating vast amounts of highly diverse data which is of
      potential interest to researchers beyond the laboratories in which it is
      collected. In particular, quantitative neuroanatomical data is relevant to a wide
      variety of areas, including studies of development, aging, pathology and in
      biophysically oriented computational modelling. Moreover, the relatively discrete
      and well-defined nature of the data make it an ideal application for developing
      systems designed to facilitate data archiving, sharing and reuse. At present, the
      only widely used forms of dissemination are figures and tables in published
      papers which suffer from inaccessibility and the loss of machine readability.
      They may also present only an averaged or otherwise selected subset of the
      available data. Numerous database projects are in progress to address these
      shortcomings. They employ a variety of architectures and philosophies, each with
      its own merits and disadvantages. One axis on which they may be distinguished is
      the degree of top-down control, or curation, involved in data entry. Here we
      consider one extreme of this scale in which there is no curation, minimal
      standardization and a wide degree of freedom in the form of records used to
      document data. Such a scheme has advantages in the ease of database creation and
      in the equitable assignment of perceived intellectual property by keeping the
      control of data in the hands of the experts who collected it. It does, however,
      require a more sophisticated infrastructure than conventional databases since the
      software must be capable of organizing diverse and differently documented data
      sets in an effective way. Several components of a software system to provide this
      infrastructure are now in place. Examples are presented, showing how these tools
      can be used to archive and publish neuronal morphology data, and how they can
      give an integrated view of data stored at many different sites.

PMID- 12222823
TI  - Content and localization of myostatin in mouse skeletal muscles during aging,
      mechanical unloading and reloading.
AB  - Changes in myostatin content and localization in mouse skeletal muscles were
      investigated during aging, hindlimb suspension (HS) and reloading after HS.
      During aging, the content of myostatin among solubilized proteins in
      gastrocnemius and plantaris muscles (Gast/Plant) was initially low and increased
      until their wet weight/body weight ratio reached a peak. It remained unchanged
      with further aging, although gradual atrophy of the muscles was seen to occur.
      Also, the myostatin content did not change significantly during HS (up to 14
      days) in both Gast/Plant and soleus muscles, though the muscles showed
      morphological signs of atrophy. However, reloading for 2 days after a 14-day HS
      caused significant decreases in the myostatin content in both of these muscles.
      Immunohistochemical observations showed the sarcoplasmic existence of myostatin,
      the amount of which appeared to decrease after reloading. The results suggest
      that myostatin plays a part in the processes of muscular growth and loading
      induced hypertrophy, but is not involved in either aging-related or unloading
      induced muscular atrophy.

PMID- 12222824
TI  - Fluorescence changes on contractile activation in TnC(DANZ) labeled skinned
      rabbit psoas fibers.
AB  - The increase in fluorescence of dansylaziridine (DANZ) labeled troponin C
      (TnC(DANZ) substituted into skinned rabbit psoas fibers was determined as a
      function of the pCa. The fluorescence data are expressed as the ratio of two
      wavelength bands, one that sees the fluorescence of TnC(DANZ), and one that sees
      background fluorescence and scatter. The percent TnC replaced with TnC(DANZ) was
      varied between 10 and 50% and, the fibers were randomly stretched, at the start
      of each experiment, between 10 and 50%. A large ratio increase accompanies
      increase in [Ca2+]. The pCa/force data are best fit by the Hill equation but the
      pCa/ratio data are best fit by a model in which Ca2+ binds in two phases. The
      position of the force curve on the pCa axis varies little between fibers, in
      contrast to that of the ratio or A-fluorescence curve. In accord with previous
      reports the delta-fluorescence can be left of the force on the pCa axis (type I)
      or superimpose in part on the force (type II). Not described previously, we find
      curves in which the second phase of the ratio cross-over the pCa/force curve.
      This type III relationship is found only in fibers less than 3 weeks postmuscle
      harvest. We propose that the first, relatively invariant, phase of the biphasic
      pCa/ratio curve accompanies Ca2+ binding to either of the two low affinity sites
      on TnC(DANZ) as it does for TnC in solution. The second, highly cooperative,
      phase of the ratio curve that accompanies muscle contraction and enhanced Ca2+
      binding is initiated when sufficient Ca2+ is bound to overcome inhibitory
      systems. Loose coupling between the initial Ca2+ binding and the cooperative
      switch point may account for much of the variation in the shape and position of
      the pCa/ratio curve. There is evidence that, in the overlap zone, weakly attached
      myosin cross-bridges enhance cooperation between the regulatory units of the thin
      filaments.

PMID- 12222826
TI  - Solution properties of full length and truncated forms of myosin subfragment 1
      from Dictyostelium discoideum.
AB  - The atomic structures for several myosin head isoforms in different nucleotide
      states have been determined in recent years. The comparison of these structures
      is complicated by the use of myosin subfragment 1 (S1) constructs of different
      length in different studies. Several atomic structures of the S1 nucleotide
      complex were obtained using Dictyostelium discoideum S1dC, a genetically
      truncated form of S1 lacking the light chain binding domain (LCBD) and both light
      chains. The goal of the present study has been to assess the effects of such a
      truncation on the solution properties of S1 and in particular, on its active
      site, actin binding site and the converter region. The nucleotide and actin
      binding properties, CD spectra and the reactivities of Lys-84 (corresponds to the
      'reactive lysine', Lys-83 in rabbit skeletal S1) and Cys-678 (corresponds to the
      'SH2-group', Cys-697 in rabbit S1) were compared for the full length (flS1) and
      the truncated (S1dC) forms of Dictyostelium S1. The two forms showed similar
      nucleotide binding properties. However, SldC had a lower structural stability and
      a significantly higher Km value for actin-activated ATPase as compared to flS1.
      Differences were found also in the near-UV CD spectrum between flS1 and S1dC. SH2
      reactivity in SldC appeared to be greatly inhibited compared with that in flS1.
      The modification of Lys-84 caused a greater increase in the MgATPase activity in
      S1dC than in flS1. ADP inhibited this activation for both SldC and flS1. Taken
      together our results identify both truncation-caused differences between S1dC and
      flS1, as well as isoform-related differences between skeletal and Dictyostelium
      S1.

PMID- 12222825
TI  - Dynamic nature of fibre-type specific expression of myosin heavy chain
      transcripts in 14 different human skeletal muscles.
AB  - The main goal of this study was to find out, whether the appearance of fibres
      without evident myosin heavy chain (MyHC) transcript expression (negative fibres)
      implies the existence of additional MyHC transcripts in human muscle fibres.
      Fourteen different skeletal muscles were analysed also to verify how MyHC
      transcript expression matches histochemical phenotypes of fibres. For this
      purpose, the expression of beta-slow, 2a and 2x MyHC transcripts, demonstrated by
      in situ hybridisation technique, was analysed within type I, IIC, IIA, IIAX and
      IIX fibres, determined according to the activity of myofibrillar ATPase.
      Additionally, MyHC isoform expression was immunohistochemically demonstrated and
      metabolic profiles of negative fibres were estimated. From a total of 4444 muscle
      fibres analysed, only 0.8% of fibres were negative, among them type I prevailed,
      the remainder were type IIA and IIX fibres. The majority of fibres expressed only
      beta, 2a and 2x MyHC transcripts and they mostly matched type I, IIA and IIX
      fibres respectively, but two minor hybrid fibre groups (beta/2a and 2ax)
      exhibited variable histochemical phenotype. The infrequency, the prevailing
      oxidative-glycolytic metabolic profile of negative type I fibres and frequent co
      appearance with transitional type IIC fibres imply that the negative fibres
      rather result from fibre type transition than express an additional slow or even
      2b MyHC transcripts. The appearance of hybrid and mismatched fibres additionally
      indicates that fibre type transition occurs also in presumably normal skeletal
      muscles, what enables the muscles to tune even with minimal changes in mechanical
      demands.

PMID- 12222827
TI  - Functional studies of yeast actin mutants corresponding to human cardiomyopathy
      mutations.
AB  - The molecular mechanisms by which different mutations in actin lead to distinct
      cardiomyopathies are unknown. Here, actin mutants corresponding to alpha-cardiac
      actin mutations causing hypertrophic cardiomyopathy [(HCM) P164A and A331P] and
      dilated cardiomyopathy [(DCM) R312H and E361G] were expressed in yeast and
      purified for in vitro functional studies. While P164A appeared unaltered compared
      to wild-type (WT) actin, A331P function was impaired. A331P showed reduced
      stability in circular dichroism melting experiments; its monomer unfolding
      transition was 10 degrees C lower compared to WT actin. Additionally, in vitro
      filament formation was hampered, and yeast cell cultures were temperature
      sensitive, implying perturbations in actin-actin interactions. Filament
      instability of the A331P mutant actin could lead to actomyosin dysfunction
      observed in HCM. Yeast strains harboring the R312H mutation did not grow well in
      culture, suggesting that cell viability is compromised. The E361G substitution is
      located at an alpha-actinin binding region where the actin filament is anchored.
      The mutant actin, though unaltered in the in vitro motility and standard
      actomyosin functions, had a threefold reduction in alpha-actinin binding. This
      could result in impairment of force-transduction in muscle fibers, and a DCM
      phenotype.

PMID- 12222828
TI  - Changes in myofibrillar structure and function produced by N-terminal deletion of
      the regulatory light chain in Drosophila.
AB  - The similarity of amino acid sequence and motifs of the N-terminal extensions of
      certain class II myosin light chains, found throughout the animal kingdom,
      suggest a common functional role. One possible role of the N-terminal extension
      is to enhance oscillatory work and power production in striated muscles that
      normally operate in an oscillatory mode. We conducted small-angle X-ray
      diffraction experiments and small-length-perturbation analysis to examine the
      structural and functional consequences of deleting the N-terminal extension of
      the myosin regulatory light chain (RLC) in Drosophila flight muscle. The in vivo
      lattice spacing of dorsal longitudinal muscle (DLM) of flies lacking the RLC N
      terminal extension (Dmlc2delta2-46) was approximately 1 nm less than that of wild
      type (48.56 +/- 0.02 nm). The myofilament lattice of detergent-treated,
      demembranated DLM swelled, with the DmlcdeltaA2-46 lattice expanding more than
      wild type and requiring roughly twice the concentration of Dextran T500 to
      restore its lattice to in vivo spacing (9-10% vs. 4% w/v). The calcium
      sensitivity and maximum amplitude of net oscillatory work near the in vivo
      lattice spacing was significantly lower in Dmlc2delta2-46 compared to wild type
      (pCa50 shifted by approximately one-third of a pCa unit; amplitude reduced by
      approximately one-half). These changes were in contrast to the lack of effect
      reported in a previous study carried out in the absence of Dextran T500. The
      results are consistent with the N-terminal extension interacting with actin to
      increase the probability that crossbridges form during stretch-activated
      oscillatory work and power production, especially at submaximal levels of calcium
      activation.

PMID- 12222830
TI  - The gradual expression of troponin T isoforms in chicken wing muscles.
AB  - Troponin T (TnT) is one of the muscle regulatory proteins and is thought to be
      related to unique contractile properties in diverse muscles and also to
      myogenesis. The expression of TnT isoforms in the chicken wing muscles was
      investigated by two-dimensional gel electrophoresis and immunoblotting with an
      antiserum against fast skeletal muscle TnT. The upper arm muscles, M. biceps
      brachii and M. triceps brachii, showed striking differential expression of high
      molecular weight B type and low molecular weight L type TnT isoforms in the
      proximal, middle and distal portions of each muscle. The ratio of the total
      quantity of B type TnT isoforms to that of L type TnT isoforms decreased
      gradually along the proximo-distal axis of the wing. The upper arm muscles, M.
      deltoideus and M. tensor patagii longus, and most of the lower arm muscles
      examined in this study did not show such differential expression. The lower arm
      muscles, M. flexor carpi ulnaris and M. extensor carpi radialis longus, showed
      some gradual expression of TnT isoforms, but the B/L ratio in the former slightly
      increased along the proximo-distal axis. The gradual expression in M. biceps
      brachii was not found in the 1-day-old chick, but was established by 30 days post
      hatching. The biological significance of differential expression of TnT isoforms
      in different muscles and even in single muscles was speculated upon with respect
      to muscle contractile regulation and myogenesis.

PMID- 12222829
TI  - Inactivation of sarcoplasmic reticulum Ca(2+)-atpase in low-frequency stimulated
      rat muscle.
AB  - Continuous low-frequency stimulation (CLFS) by implanted electrodes for 12-24 h
      led to a significant (approximately 30%) decrease in the activity of sarcoplasmic
      reticulum Ca(2+)-ATPase in fast-twitch extensor digitorum longus (EDL) and
      tibialis anterior (TA) muscles of intact rats. The decline in catalytic activity
      after 24 h of CLFS was accompanied by an approximately twofold increase in
      dinitrophenylhydrazine-reactive carbonyl groups of the enzyme. It also correlated
      with an immunochemically determined 30% decrease in Ca2(+)-ATPase protein.
      Recovery studies after 12 h of CLFS revealed a relatively slow (48-72 h) re
      establishment of normal catalytic activity. These findings suggest that the 30%
      decline of Ca(2+)-ATPase activity in low-frequency stimulated rat muscle led to
      an irreversible modification by protein oxidation. The decrease in Ca(2+)-ATPase
      protein most likely resulted from the degradation of inactive Ca(2+)-ATPase
      molecules. The relatively slow recovery of Ca(2+)-ATPase activity suggests that
      de novo synthesis of the enzyme may be necessary to re-attain normal activity.

PMID- 12222832
TI  - Women and smoking: a report of the Surgeon General. Executive summary.
AB  - This is the second report of the U.S. Surgeon General devoted to women and
      smoking. The first was published in 1980 (U.S. Department of Health and Human
      Services [USDHHS] 1980), 16 years after the initial landmark report on smoking
      and health of the Advisory Committee to the Surgeon General appeared in 1964
      (U.S. Department of Health, Education, and Welfare [USDHEW] 1964). The 1964
      report summarized the accumulated evidence that demonstrated that smoking was a
      cause of human cancer and other diseases. Most of the early evidence was based on
      men. For example, the report concluded, "Cigarette smoking is causally related to
      lung cancer in men.... The data for women, though less extensive, point in the
      same direction" (USDHEW 1964, p. 37). By the time of the 1980 report, the
      evidence clearly showed that women were also experiencing devastating health
      consequences from smoking and that "the first signs of an epidemic of smoking
      related disease among women are now appearing" (USDHHS 1980, p. v). The evidence
      had solidified later among women than among men because smoking became
      commonplace among women about 25 years later than it had among men. However, it
      was still deemed necessary to include a section in the preface of the 1980 report
      titled "The Fallacy of Women's Immunity." In the two decades since, numerous
      studies have expanded the breadth and depth of what is known about the health
      consequences of smoking among women, about historical and contemporary patterns
      of smoking in demographic subgroups of the female population, about factors that
      affect initiation and maintenance of smoking among women (including advertising
      and marketing of tobacco products), and about interventions to assist women to
      quit smoking. The present report reviews the now massive body of evidence on
      women and smoking-evidence that taken together compels the Nation to make
      reducing and preventing smoking one of the highest contemporary priorities for
      women's health.

PMID- 12222831
TI  - Post-tetanic potentiation increases energy cost to a higher extent than work in
      rat fast skeletal muscle.
AB  - We studied the effects of (post-tetanic) potentiation on myosin light chain (MLC
      2) phosphorylation, work and energy cost in skeletal muscle. Experiments were
      performed using in situ medial gastrocnemius muscles of male Wistar rats, which
      were electrically stimulated through the severed sciatic nerve. One group of
      muscles was first potentiated with an isometric tetanus before a series of 10
      concentric contractions (PRC). A second group performed the same series of
      contractions without previous potentiation (RC). Following the last contraction
      the muscles were rapidly frozen and excised after which the high-energy phosphate
      content, lactate concentration and the level of MLC-2 phosphorylation were
      measured. The results indicate that PRC muscles had a higher (P < 0.05) total
      work output 144.5 +/- 17.0 (SD) (n = 6) vs. 121.6 +/- 11.4 (SD) (n = 6) mJ and
      level of MLC-2 phosphorylation (49.2 +/- 7.3 vs. 40.8 +/- 3.6%) than RC muscles.
      The energy cost of the series of concentric contractions in the PRC muscles (9.8
      +/- 1.9 micromol approximately P/muscle) was significantly higher (P < 0.05) than
      the energy cost in the RC muscles (6.2 +/- 0.97 micromol approximately P/muscle).
      It was shown that the relative increase in energy cost of PRC muscles was higher
      (P < 0.05) than in total work output. It is proposed that the relative high
      increase in energy cost is the direct result of the increase in muscle
      performance rather than a property of potentiation.

PMID- 12222833
TI  - Spatial expression of VEGF-A in human glioma.
AB  - Astrocytoma, especially of high grade, is dependent on neovascularization for its
      growth and progression. The expression of vascular endothelial growth factor
      (VEGF-A), an important angiogenesis factor, has been demonstrated in perinecrotic
      cells in glioblastoma. In order to achieve more knowledge regarding the process
      of astrocytoma angiogenesis and growth we have investigated the expression of
      VEGF-A immunohistochemically in different areas of tumors. In 21 patients with
      astrocytomas of varying grade serial stereotactic biopsies were performed.
      Biopsies were taken from brain adjacent to tumor (BAT), tumor periphery, and
      tumor center. In the BAT region of high-grade astrocytomas, we found a frequent
      expression of VEGF-A in tumor cells and less frequent in blood vessels. In the
      periphery, there was an expression mainly in tumor cells while in the center of
      grade IV tumors VEGF-A was also frequently expressed in cells adjacent to
      necrosis. VEGF-A in astrocytoma grade II was demonstrated in viable tumor cells
      preferentially in the periphery but also in peripheral vessels and in centrally
      located tumor cells. The findings indicate that, in addition to hypoxia in
      necrotic areas there may be other factors that stimulate the expression of VEGF
      A. It is suggested that VEGF-A may be a prerequisite for the aggressive and
      infiltrative growth of astrocytomas. Therefore, when operating high-grade
      astrocytomas it may be of importance to resect this aggressive peripheral part of
      the tumor and also to take this finding into account when planning radiotherapy.

PMID- 12222834
TI  - The hyaluronan receptor RHAMM/IHABP in astrocytoma cells: expression of a tumor
      specific variant and association with microtubules.
AB  - Hyaluronan binding to its cellular receptors CD44 and ICAM-1 appears to enhance
      the malignant behavior of tumors, including astrocytomas. RHAMM/IHABP, another
      hyaluronan receptor, has been identified in breast carcinoma cells, but its
      presence in astrocytomas is yet undetermined. Herein, we report that a monoclonal
      antibody against plectin (a cytoskeletal protein linker) recognizes on Western
      blots of U-373 MG glioblastoma cells, a 300-kDa band corresponding to plectin and
      two bands of 86 and 70 kDa. cDNA cloning and Northern blotting reveals that these
      two bands represent isoforms of RHAMM/IHABP. Sequence comparisons suggest that
      the plectin monoclonal antibody recognizes RHAMM/IHABP because this protein and
      plectin share short peptide sequences of similar primary and secondary structure.
      Western blotting demonstrates that most human astrocytoma tissues and cell lines
      express the 86- and 70-kDa isoforms of RHAMM/IHABP. Interestingly, the 70-kDa
      variant is undetectable in normal brain tissues and in primary cultures of
      astrocytes suggesting that its expression is tumor-specific. Transfection
      experiments with epitope-tagged RHAMM/IHABP cDNA established that RHAMM/IHABP
      associates with microtubules in astrocytoma cells, while in normal astrocytes it
      either co-localizes with microtubules or has a diffuse cytoplasmic distribution.
      This suggests that RHAMM/IHABP has the capacity to bind to microtubules in normal
      and transformed astrocytes, and that neoplasia may favor this association.

PMID- 12222835
TI  - Apoptosis and survival in high-grade astrocytomas as related to tumor Fas (APO
      1/CD95) expression.
AB  - Although a majority of high-grade gliomas express the apoptosis-inducing receptor
      Fas, little is known about the extent of apoptosis or prognostic significance of
      Fas expression in these tumors. In situ labeling of apoptotic cells and Ki-67
      immunohistochemistry were performed on 51 high-grade human astrocytomas
      previously characterized for Fas expression. Survival data was compiled from
      patient records and correlated with tumor grade, apoptotic index (AI) and Fas
      expression. A significant correlation was found between tumor grade and the AI
      and Ki-67 labeling index (LI); however, only the AI increased significantly with
      Fas expression. The AI increased from 0.39 +/- 0.12% to 0.82 +/- 0.10% in grade
      III vs. IV astrocytomas (P = 0.003). The Ki-67-LI increased from 3.64 +/- 1.5% to
      11.35 +/- 2.1% in grade III vs. IV astrocytomas (P = 0.004). Additionally, tumors
      expressing higher Fas levels had a greater AI than those expressing lower levels
      (0.81 +/- 0.11% vs. 0.43 +/- 0.11%) (P = 0.017). Despite longer median survivals
      for patients with tumors exhibiting high Fas expression, statistical significance
      was not achieved. Patients with grade III astrocytomas demonstrated a median
      survival of 20 vs. 18 months for tumors with high vs. low Fas expression (P =
      0.51). Patients with grade IV astrocytomas demonstrated a median survival of 9
      vs. 7.4 months for tumors with high vs. low Fas expression, respectively (P =
      0.77). Although the degree of Fas expression in high-grade astrocytomas appears
      to correlate with the apoptotic rate, no overall differences in survival could be
      demonstrated between tumors expressing high vs. low Fas levels.

PMID- 12222836
TI  - A relapsed non-Hodgkin lymphoma presenting as panhypopituitarism successfully
      treated by chemotherapy.
AB  - We report a case of relapsed large B-cell non-Hodgkin lymphoma (NHL) affecting
      the anterior pituitary. The NHL relapsed after three years in complete remission.
      The patient was a 72-year-old woman who presented fever, weakness, hyponatremia,
      and hypotension. The levels of thyroid-stimulating hormone and gonadotropins were
      very low and magnetic resonance imaging showed infiltration of the pituitary
      gland and stalk. After controlling the hormonal deficiencies with substitution
      using hydroxycortisone and levothyroxin, the patient was treated with combination
      chemotherapy using cyclophosphamide, vincristine, mitoxantrone, etoposide, and
      bleomycin (VNCOP-B regimen), achieving a complete regression of the pituitary
      mass and partial recovery of the endocrine function. Lymphoproliferative
      disorders affecting the anterior pituitary are exceedingly rare, with only six
      cases in immunocompetent adults reported in the literature. To our knowledge this
      is the first report of a relapsed NHL presenting by hypopituitarism.

PMID- 12222837
TI  - Validation of the Medical Research Council and a newly developed prognostic index
      in patients with malignant glioma: how useful are prognostic indices in routine
      clinical practice?
AB  - Although different prognostic indices for malignant gliomas have been developed,
      their validity outside of clinical trials has not been widely tested. The aim of
      this study was to determine whether the Medical Research Council (MRC) brain
      tumour prognostic index was able to stratify patients for survival managed in
      routine practice, and secondly to compare the results with our newly developed
      prognostic score which included tumour grade and only 3 prognostic groups. The
      MRC and the new prognostic index were calculated for a group of 119 adult
      patients with malignant glioma managed by surgical resection/biopsy and post
      operative radiotherapy. For the MRC and new score, 6 and 3 prognostic groups were
      defined, respectively. For all patients median survival was 11 (2-66) months. The
      overall survival rate at 12 and 24 months were 43% and 18%, respectively. The MRC
      median and two-year survival rates were 14 months and 26% for a score of 1-10, 14
      months and 27% for a score of 11-15, 13 months and 22% for a score of 16-20, 8
      months and 10% for a score of 21-25, 8 months and 0% for those scoring 26-33.
      There was only one patient in the 34-38 group. For the new prognostic index,
      median and two-year survival rates were respectively 16 and 26%; 12 and 23%; 8
      and 7% for the good, intermediate and poor prognostic groups. Both indices were
      significant factors for survival in univariate analysis (MRC index, p = 0.0089,
      new index p = 0.0002), but not in multivariate analysis. Both the MRC and our
      newly devised prognostic score were able to separate patients into good and poor
      prognostic groups, which may aid in treatment decisions, although there was less
      differentiation between the MRC groups especially over the first year. Both
      scores use routinely available factors. However, inclusion of tumour grade in the
      new score may be an advantage over the MRC index.

PMID- 12222838
TI  - Are childhood and adult medulloblastomas different? A comparative study of
      clinicopathological features, proliferation index and apoptotic index.
AB  - Childhood medulloblastomas have been suspected to be biologically different from
      adult tumors, though comparative studies are sparse in the literature. The
      present study aims to establish any differences or nexus in the biological
      characteristics between childhood and adult medulloblastomas. A total of 181
      medulloblastomas were studied with respect to clinical and histological
      characteristics, MIB-1 labeling index (MIB-1 LI), apoptotic index (AI), ratio of
      apoptotic to LI, p53 and Bcl-2 protein expressions. Two-thirds (112) of the 181
      medulloblastomas occurred in children (< or = 15 years) and 69 in adults (> 15
      years). Childhood tumors were more commonly of classical histology and midline
      location while the desmoplastic variant and lateral location occurred more
      frequently in adults. Adult medulloblastomas were biologically less aggressive,
      having lower growth rate parameters (mean MIB-1 LI 19.1 +/- 15.7; AI 3.73 +/-
      2.71 and AI:LI 0.207 +/- 0.162) as compared to childhood tumors (mean MIB-1 LI
      28.3 +/- 20.4; AI 2.86 +/- 2.14 and AI:LI 0.108 +/- 0.111). p53 and Bcl-2 protein
      expressions were infrequent in all groups of tumors. No difference was noted in
      any of the parameters when classical and desmoplastic medulloblastomas were
      compared as a whole. But when compared between the age groups, an interesting
      observation (hitherto unreported in English literature) was that both classical
      and desmoplastic variants of childhood medulloblastomas had higher LI, lower AI
      and lower AI:LI ratio than their counterparts in adults, indicating that
      differences in growth rates cannot be attributed to differences in the frequency
      of occurrence of the histological variants in the two age groups. Thus, this
      study conclusively shows that there is a biological difference between childhood
      and adult medulloblastomas which is independent of standard histology and
      appeared to be associated more with age-related factors. This also warrants less
      aggressive therapy for adult medulloblastoma.

PMID- 12222839
TI  - Good clinical course in infants with desmoplastic cerebral neuroepithelial tumor
      treated by surgery alone.
AB  - We investigated why surgery alone provides for a benign clinical course in
      patients with desmoplastic infantile ganglioglioma and astrocytoma (DIG/A). The
      clinical course of 4, less than six-month-old girls, surgically treated at our
      institutions, was evaluated retrospectively. All presented with the clinical
      symptom of increasing head circumference. CT and MRI scans revealed a solid tumor
      attached to the dura that was surrounded by large, multiple cysts, in fronto
      temporo-parietal lobe. Gross total removal succeeded in all 4 cases because the
      solid components of the tumor were very firm in contrast to the soft adjacent
      brain tissue. Microscopically, the surgical specimens consisted almost entirely
      of dense fibrous connective tissue containing generally elongate cells with
      inconspicuous cytoplasm. Most of these cells were immunopositive for GFAP. There
      was no evidence of tumor cells in the cyst wall. In 3 cases, some small neurons
      were positive for neurofilament immunostain. A high proportion of
      undifferentiated small cells in a less demoplastic area far from the dura were
      immunopositive for MIB-1. All of the 4 patients have been free of recurrence for
      more than five years. In patients with DIG/A, there are 5 reasons for a good
      clinical course. [1] At surgery, the tumor margin is clearly discernible because
      of the difference between the solid tumor and the soft adjacent brain tissue. [2]
      The tumor is located in the superficial cerebral hemisphere. [3] Large, multiple
      cysts surround the tumor. [4] The growth point appears to be adjacent to the
      cysts. [5] The cyst walls are free of invading tumor cells.

PMID- 12222840
TI  - Suppression of Cdc2 dephosphorylation at the tyrosine 15 residue during
      nitrosourea-induced G2M phase arrest in glioblastoma cell lines.
AB  - We examined the mechanism of action of nitrosoureas as represented by 1-(4-amino
      2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) with
      respect to p53 and the G2M cell cycle checkpoint using two glioblastoma cell
      lines: U251MG and U373MG, with mutated p53. At log-phase cell growth, fresh
      medium containing ACNU (final concentration, 3, 10, or 30 microg/ml) was added.
      After 24 h of incubation, cells were harvested for flow cytometric or Western
      analysis. In both lines, cell numbers in the G0/G1 phase decreased with ACNU
      treatment. Cells accumulated in G2M and S phases, and the peak was shifted from
      G2M to the S phase in a concentration-dependent manner. In both cell lines, the
      amount of Cdc2 protein phosphorylated at the tyrosine 15 residue was increased 2-
      to 6-fold by treatment with ACNU compared with untreated control cells.
      Expression of cyclin B protein was suppressed in cells treated with 30 microg/ml
      ACNU. Protein abundance for total Cdc2, Cdc2 phosphorylated at the threonine 161
      residue, Wee 1, Myt 1, Chk 1, and 14-3-3sigma was not affected by treatment with
      ACNU in either cell line. We suggest that a low concentration of ACNU should be
      used with adjuvant therapies that act upon cells in the G2M phase. A high
      concentration of ACNU should be used with adjuvant therapies that act upon cells
      in the S phase.

PMID- 12222841
TI  - Pleomorphic primitive neuroectodermal tumor with glial and neuronal
      differentiation: clinical, pathological, cultural, and chromosomal analysis of a
      case.
AB  - This paper examines a case of pleomorphic primitive neuroectodermal tumor (PNET)
      with glial and neuronal differentiation in a 7-year-old girl who was
      clinicopathologically reported with immunohistochemical and chromosomal analysis.
      Clinically, a highly aggressive behavior leading to early recurrence with
      cerebrospinal fluid seedings was characteristic despite total removal and
      chemoradiation therapy. Pathologically, severe pleomorphism was noted and large
      ganglioid cells were predominant. Immunohistochemically, the expression of low
      molecular neurofilament was recognized in the surgical specimens and increased in
      the recurrence. Coexpression of vimentin and neurofilament/GFAP was recognized in
      the culture. Chromosomal analysis showed near-diploidy, but different karyotype
      from that PNETs previously reported. These findings suggested that PNETs with
      pleomorphism and differentiation into both glial and neuronal lineages may show
      aggressiveness and require more aggressive therapy.

PMID- 12222842
TI  - Use of 201Tl SPECT imaging to assess the response to therapy in patients with
      high grade gliomas.
AB  - PURPOSE: To assess the potential role of 201Tl single photon emission tomography
      (201-Thallium SPECT) when compared to other imaging modalities in the evaluation
      of the response to therapy in high grade gliomas. MATERIALS AND METHODS: Twenty
      patients with histologically proved high grade glioma have been included: 15 with
      glioblastoma (GBM), 3 with anaplastic astrocytoma (AA) and 2 with anaplastic
      oligoastrocytoma (AOA). Patients were assessed by 201Tl SPECT, computed
      tomography (CT) and magnetic resonance imaging (MRI) at (a) either at the moment
      of maximum response to first line chemotherapy, or after the completion of
      radiotherapy and chemotherapy if post-surgical residual disease was present, and
      (b) after the completion of second line chemotherapy if disease persisted, or
      either a relapse or disease progression was confirmed. Final response was
      evaluated according to the McDonald criteria, and by comparing SPECT, CT and MRI
      results. RESULTS: According to the McDonald criteria, clinical response after
      first line chemotherapy was 5 partial response, 7 stable disease and 8
      progressive disease. Evaluation by 201Tl SPECT was in agreement with such
      criteria in nearly all patients (90%). MRI findings closely agreed with the
      clinical follow-up. CT findings clearly differed from those observed by SPECT and
      MRI. After second line therapy, 10 patients progressed, 3 had stable disease and
      7 had partial response. 201Tl SPECT agreed with the clinical status in 89% cases,
      whereas MRI and, specially CT, fared significantly lower. CONCLUSION: Compared to
      conventional neuroimaging, 201Tl SPECT added valuable information in the
      assessment of the response to therapy in our patient population; whenever
      findings were not conclusive and in the case of disagreement between CT and MRI
      findings.

PMID- 12222843
TI  - Availability of emergency contraceptive pills at university and college student
      health centers.
AB  - The author used the stages of change model to determine how ready student health
      centers at surveyed universities and colleges were to make emergency
      contraceptive pills (ECPs) available to students. Of the 358 centers that
      responded, 52.2% offered ECPs and 47.8% did not. The benefits of offering ECPs
      were listed as pregnancy prevention, the opportunity to introduce students to
      traditional contraception methods, and students' appreciation. Barriers to
      offering ECPs included institutions' religious affiliations, clinic and
      administrative staff objections, inability to prescribe or dispense medications,
      fear of liability, concern that ECPs would undermine students' use of traditional
      contraception methods, and no expressed need. Whether ECPs were available was
      associated with demographic characteristics of the institutions that responded,
      including geographic region, type of institution, size of student population, and
      students' status as commuter or on-campus residents.

PMID- 12222844
TI  - Stages of change among ethnically diverse college students.
AB  - The authors applied the stage-of-change construct in the transtheoretical model
      to examine the distribution of Asian (n = 869), African American (n = 373), White
      (n = 1322), and Hispanic (n = 535) American undergraduate students across the 5
      stages of change for exercise. Stage of change varied as a function of ethnicity.
      Higher percentages of minorities were in the precontemplation and contemplation
      stages. The likelihood of being in these stages was from 43% to 82% greater for
      minorities than for White students. Also examined were the congruency between
      stage of change and self-reported levels of physical activity. Half of the
      sedentary students and 15.6% of the active students were misclassified by the
      stage-of-change procedure. Misclassification rates were higher for minority women
      (27.8%) than for White women (17.8%) and for Asian students (24.6%) compared with
      all others (20.6%). The results of this study have implications for the design of
      physical activity interventions based on stage of change.

PMID- 12222845
TI  - An evaluation of physical fitness parameters for graduate students.
AB  - Although graduate physical therapy students are taught the principles of fitness
      for incorporation into their professional lives, they have difficulty finding the
      time to implement these principles during graduate school. The authors studied 3
      successive classes of graduate physical therapy students at the beginning and
      ending of their respective programs. They found that the women's percentages of
      body fat were significantly greater over the period of the study. The men's lower
      extremity strength decreased at the slower speeds (60 degrees/second), and the
      women showed increased strength at the higher speeds (180 and 240 degrees/second,
      respectively). Male grip strength significantly increased over the period of the
      study. To decrease students' percentages of body fat and increase their strength,
      the authors asserted that physical therapy students should be allowed more time
      to participate in fitness activities during their graduate school years.

PMID- 12222846
TI  - Assessing student staff motivation and satisfaction to strengthen health
      education services.
AB  - A student staff inquiry project in the department of health education at a large
      state university assessed the motivation and satisfaction of student staff and
      peer educators. The students who managed this Student Inquiry Project created the
      interview tool, collected and analyzed the data for themes, and developed follow
      up recommendations. Through this student-driven qualitative process, several
      themes emerged, including the need for more department visibility, student
      opportunities, student identity, skill building, and appreciation. The department
      is using the recommendations to strengthen student connection, satisfaction, and
      training.

PMID- 12222847
TI  - Is it really our chemicals that need balancing?

PMID- 12222848
TI  - Links between past abuse, suicide ideation, and sexual orientation among San
      Diego college students.
AB  - The authors explored relationships among childhood abuse, suicidal ideation, and
      sexual orientation of 18- to 30-year-old students enrolled in 2 San Diego area
      colleges, using responses from anonymous questionnaires. Sixty percent of the 138
      eligible respondents were women, and 22% were self-identified gay/bisexual
      individuals. Women were more likely than men to report at least 1 form of
      emotional abuse (odds ratio [OR] = 2.3; p =.02) and unwanted sexual touching (OR
      = 4.3; p = .0004). Lesbian/bisexual women were significantly more likely to
      report past suicidal ideation than were heterosexual women (OR = 3.7, p = .03).
      Gay/bisexual men were more likely to report unwanted sexual touching than were
      heterosexual men (OR = 5.1, p = .04), but the men did not report significantly
      higher rates of past suicide ideation or suicide attempts. Sexual orientation and
      a past history of child sexual, physical, and emotional abuse could be
      compounding risk factors for suicidal ideation among college students.

PMID- 12222849
TI  - Fine resolution calculations of SAR in the human body for frequencies up to 3
      GHz.
AB  - Finite-difference time-domain (FDTD) calculations of whole-body averaged specific
      energy absorption rate (SAR) have been performed from 100 MHz to 3 GHz at the
      basic 2 mm resolution of the voxel (volume pixel) model NORMAN without any
      rescaling to larger cell sizes. The reduction in the voxel size from previous
      work allows SAR to be calculated at higher frequencies. Additionally, the
      calculations have been extended down to 10 MHz, covering the whole-body resonance
      regions at a resolution of 4 mm. As well as for the adult phantom, SAR values are
      calculated for scaled versions representing 10-, 5- and 1-year-old children for
      both grounded and isolated conditions. External electric field levels are derived
      from limits of whole-body averaged SAR and localized SAR in the ankle, and
      compared with NRPB investigation levels and ICNIRP reference levels. The ICNIRP
      field reference levels alone would not provide a conservative estimate of the
      localized SAR exposure in the leg for grounded conditions. It would be necessary
      to invoke the secondary reference level on limb current to provide compliance
      with basic restrictions on localized SAR averaged over 10 g.

PMID- 12222850
TI  - Bulk optical properties of healthy female breast tissue.
AB  - We have measured the bulk optical properties of healthy female breast tissues in
      vivo in the parallel plate, transmission geometry. Fifty-two volunteers were
      measured. Blood volume and blood oxygen saturation were derived from the optical
      property data using a novel method that employed a priori spectral information to
      overcome limitations associated with simple homogeneous tissue models. The
      measurements provide an estimate of the variation of normal breast tissue optical
      properties in a fairly large population. The mean blood volume was 34 +/- 9
      microM and the mean blood oxygen saturation was 68 +/- 8%. We also investigated
      the correlation of these optical properties with demographic factors such as body
      mass index (BMI) and age. We observed a weak correlation of blood volume and
      reduced scattering coefficient with BMI: correlation with age, however, was not
      evident within the statistical error of these experiments. The new information on
      healthy breast tissue provides insight about the potential contrasts available
      for diffuse optical tomography of breast tumours.

PMID- 12222851
TI  - Monte Carlo modelling of the spectral reflectance of the human eye.
AB  - The interpretation of in vivo spectral reflectance measurements of the ocular
      fundus requires an accurate model of radiation transport within the eye. As well
      as considering the scattering and absorption processes, it is also necessary to
      account for appropriate histological variation. This variation results in
      experimentally measured spectra which vary, both with position in the eye, and
      between individuals. In this paper the results of a Monte Carlo simulation are
      presented. Three histological variables are considered: the RPE melanin
      concentration, the choriodal haemoglobin concentration and the choroidal melanin
      concentration. By considering these three variables, it is possible to generate
      model spectra which agree well with in vivo experimental measurements of the
      nasal fundus. The model has implications for the problem of extracting
      histological parameters from spectral reflectance measurements. These
      implications are discussed and a novel approach to interpretation of images of
      the ocular fundus suggested.

PMID- 12222852
TI  - Influence of high-energy photon beam irradiation on pacemaker operation.
AB  - In this paper, we determine the influence of high-energy photon beam irradiation
      used for external radiotherapy on pacemakers, at different doses and dose rates.
      Ninety-six pacemakers of various origins and ages underwent in vitro high-energy
      photon irradiation under technical conditions close to external radiotherapy,
      using a linear accelerator delivering photons of high energy (18 MV). Various
      dose levels (up to 200 Gy for certain particularly resistant pacemakers) were
      delivered to pacemakers located in a water-equivalent phantom with several dose
      rates (from 0.05 to 8 Gy min(-1)). Observed failures were sorted into eight
      classes of progressive harmfulness, some of them possibly lethal. One irradiated
      pacemaker exhibited an important defect at a dose rate of 0.2 Gy min(-1), for a
      cumulative dose of 0.15 Gy. Two pacemakers showed an important defect at a
      cumulative dose of 1 Gy, while nine pacemakers failed at a cumulative dose lower
      than or equal to 2 Gy and 13 failed at a cumulative dose lower than or equal to 5
      Gy. The most important failure probability (70% of irradiated pacemakers) is
      observed for 8 Gy min(-1), whereas no pacemakers failed at a dose rate lower than
      or equal to 0.2 Gy min(-1). In conclusion, warnings given by manufacturers about
      the maximum tolerable cumulative radiation doses for safe operation of irradiated
      pacemakers (5 Gy), even reduced to 2 Gy, are not reliable. The spread of
      cumulative doses inducing failures is very large since our observations show an
      important failure at 0.15 Gy, while ten pacemakers withstood more than 140 Gy of
      cumulative dose. The safe operation of pacemakers under irradiation depends
      mainly on type and model. It depends also on dose rate. From our observations,
      for the safe operation of pacemakers, a recommendation of a maximum dose rate of
      0.2 Gy min(-1) rejecting direct irradiation of the pacemaker at a standard dose
      rate for tumour treatment (2 Gy min(-1)) is made.

PMID- 12222853
TI  - Dosimetry using plane-parallel ionization chambers in a 75 MeV clinical proton
      beam.
AB  - Reference ionization chamber dosimetry in clinical proton beams is generally
      performed with cylindrical ionization chambers. However, when the measurement is
      performed in the presence of a large depth dose gradient or in a narrow spread
      out Bragg peak (SOBP), it could be advisable to use a plane-parallel chamber. Few
      recommendations and studies have been devoted to this subject. In this paper,
      experimental information on perturbation correction factors for four plane
      parallel ionization chamber types in proton beams is presented. The experiments
      were performed in 75 MeV modulated and non-modulated proton beams. Monte Carlo
      calculations have been performed to support the conclusions of the experimental
      work. Overall, we were not able to find experimental evidence for significant
      differences between the secondary electron perturbation correction factors for
      plane-parallel chambers and those for a cylindrical NE2571. We found experimental
      ratios of perturbation correction factors that did not differ by more than 0.6%
      from unity for a Roos and two NACP02 chambers, and by not more than 1.2% for a
      Calcam-2 and two Markus chambers. Monte Carlo simulations result in corrections
      that are limited to 0.6% in absolute value, but given the overall uncertainties
      of the measurements, the deviations of the correction factors from unity could
      not be resolved from the experimental results. The results of the simulations
      thus support the experimental conclusion that perturbation correction factors for
      the set of plane-parallel chambers in both proton beams (relative to NE2571) do
      not deviate from unity by more than 1.2%. This confirms, within the experimental
      uncertainties, the assumption that the overall perturbation correction factor for
      a plane-parallel chamber in a low-energy proton beam is unity, made in IAEA TRS
      398 and other dosimetry protocols. Given the large uncertainties of the gradient
      correction factors to be applied when using a cylindrical ionization chamber in a
      narrow SOBP or in the presence of a strong depth dose gradient, the level of
      agreement between plane-parallel and cylindrical ionization chambers observed in
      this study shows that plane-parallel chambers are a reliable alternative for
      reference dosimetry in low-energy proton beams.

PMID- 12222854
TI  - Optimization of the composition of phantom materials for computed tomography.
AB  - Using available data for photon attenuation and tissue composition, a computer
      code was developed for the optimization of the composition of phantom materials
      for diagnostic radiology. The code allows selection of attenuation data in a
      photon energy range from 1 to 150 keV and the choice of a suitable weight
      function in the energy interval chosen. For applications in CT imaging a weight
      function is available reflecting the contribution of the x-ray spectrum to the CT
      signal. Several phantom materials for CT were optimized (body fat, trabecular
      bone, an average bone composition for C4 vertebrae and water) by varying the
      mineral components in a polymer base in order to adjust x-ray attenuation
      properties. Measurements with the water equivalent material (PSPP1) showed good
      agreement of calculated and measured HU values (AHU = 7.3 +/- 5.3 at 80 kVp and
      4.0 +/- 2.7 at 140 kVp) and little variation of HU for tube voltages from 80 to
      140 kVp. The method provides a fast and flexible means for obtaining optimized
      phantom materials for a large variety of tissue compositions and energy ranges.

PMID- 12222855
TI  - Temperature dependence of HU values for various water equivalent phantom
      materials.
AB  - The temperature dependence of water equivalent phantom materials used in
      radiotherapy and diagnostic imaging has been investigated. Samples of phantom
      materials based on epoxy resin, polyethylene, a polystyrene-polypropylene mixture
      and commercially available phantom materials (Solid Water, Gammex RMI and Plastic
      Water, Nuclear Associates) were scanned at temperatures from 15 to 40 degrees C
      and HU values determined. At a reference temperature of 20 degrees C materials
      optimized for CT applications give HU values close to zero while the commercial
      materials show an offset of 119.77 HU (Plastic Water) and 27.69 HU (Solid Water).
      Temperature dependence was lowest for epoxy-based materials (EPX-W: -0.23 HU
      degrees C(-1); Solid Water: -0.25 HU degrees C(-1)) and highest for a
      polyethylene-based material (X0: -0.72 HU degrees C(-1)). A material based on a
      mixture of polystyrene and polypropylene (PSPPI: -0.27 HU degrees C(-1)) is
      comparable to epoxy-based materials and water (-0.29 HU degrees C(-1)).

PMID- 12222856
TI  - The use of a reflective scanner to study radiochromic film response.
AB  - GafChromic MD-55-2 film response was studied using a flatbed, reflective Microtek
      ScanMaker E3 scanner, under different conditions to optimize its use.
      Irradiations were performed using 60Co gamma rays in a 0-300 Gy dose interval to
      produce a calibrated step wedge. A 24-bit colour-scale mode along with image
      splitting into its red, green and blue components is suggested as an improved
      dosimetry method over a 256 grey level (8-bit) mode, extending the dynamic range
      for this film. Diverse film orientation and positioning, a black or a white
      background, and individual step film scanning were evaluated. Unwanted
      normalization is overcome by adding reference black and white steps adjacent to
      the radiochromic film, ensuring reproducibility. The use of a red filter was
      found to be equivalent to the use of the red component of the image after image
      colour splitting. The useful range for MD-55-2 film is extended up to 300 Gy if
      colour components, other than red, are used to evaluate the response. Comparisons
      with optical density measurements show that inexpensive commercial scanners might
      be a good alternative to densitometers.

PMID- 12222857
TI  - Spatial resolution in fast time-resolved transillumination imaging: an
      indeterministic Monte Carlo approach.
AB  - The spatial resolution achievable in time-resolved optical transillumination
      imaging through a turbid (scattering and absorbing) medium has been reassessed
      theoretically. The temporal point spread function was constructed assuming a
      delta function input pulse, a approximately 50 mm thick medium and a small
      detector with zero risetime. Temporal profiles were derived from an
      indeterministic Monte Carlo simulation for different time scales. From the
      temporal point spread function (TPSF), an analytic edge response function from
      which the spatial resolution was determined was derived. Previous analytical
      methods for determining the spatial resolution are approximations for very short
      flight times (sub-100 ps time region). The results show that a spatial resolution
      of about two millimetres is possible under ideal signal-to-noise ratio conditions
      and with detector gate times of the order of ten picoseconds. If this predicted
      spatial resolution can be achieved in an imaging system, it may be possible to
      improve the diagnosis of breast tumours.

PMID- 12222858
TI  - Fast implementation of the single scatter simulation algorithm and its use in
      iterative image reconstruction of PET data.
AB  - In positron emission tomography (PET), scatter correction is usually performed
      prior to image reconstruction using a more or less exact model of the scatter
      processes. These models require estimates of the true activity and object density
      distributions of the imaged object. The problem is that these estimates are
      computed from measured data and, therefore, already contain scattered events. The
      purpose of this work was to overcome this problem by incorporating scatter
      characteristics directly into the process of iterative image reconstruction. This
      could be achieved by an optimized implementation of the single scatter simulation
      (SSS) algorithm, which results in a significant speed-up of the scatter
      estimation procedure. The scatter simulation was then included in the forward
      projection step of maximum likelihood image reconstruction. The results
      demonstrate that this approach leads to a more exact estimation of the scatter
      component which cannot be obtained by a simple sequential data processing
      strategy.

PMID- 12222859
TI  - Measurements of MTF and SNR(f) using a subtraction method in MRI.
AB  - A method was developed for accurate measurement of the modulation transfer
      function (MTF) and signal-to-noise ratio in the spatial frequency domain (SNR(f))
      of magnetic resonance images (MRI). The MTF was calculated from the complex
      images of a line object which were obtained by the subtraction of two separately
      acquired data sets of a specially designed phantom with a sliding sheet.
      Moreover, the SNR(f) was calculated from the MTF and Wiener spectrum, both of
      which were determined using the same phantom configuration. The MTFs and SNR(f)s
      in the conventional spin-echo (SE) and turbo SE, in which the effective echo time
      was set to the first echo, were evaluated by changing the T2 of the phantom and
      the echo train length. The MTFs in the positive and negative frequencies
      indicated the effect of the k-space trajectory for each pulse sequence. SNR(f)s
      gave spatial frequency information that was not obtained with conventional
      methods. In this method, the influence of image nonuniformity and unwanted
      artefacts (edge and ghost) could be eliminated. An analysis of the MTF and the
      SNR in the spatial frequency domain provides additional information for the
      assessment of image quality in MRI.

PMID- 12222860
TI  - Radiofrequency heating effects around resonant lengths of wire in MRI.
AB  - Several recent reports agree that the potentially dangerous heating around
      extended wires or coaxial cables inside the bodycoil of a magnetic resonance
      imager is related to resonant effects. No quantitative description of this idea
      has been given so far. We analyse a simplified situation, where a straight
      metallic wire is completely surrounded by a large volume of homogeneous
      dielectric with a small conductivity. If it has the correct length, the wire acts
      as a receiving-and-retransmission antenna, changing the axial symmetry of the
      incoming electric field into a radially outgoing electric field near the wire
      ends. The latter field points into the conducting surroundings, causing
      dissipation. Some simple experiments on geometries related to this theoretical
      model provide support to the main conclusions. These suggest that under actual
      imaging conditions resonant effects might be avoided by choosing a wire length of
      about 2 m. However, more experimental work remains to be done to validate this
      suggestion.

PMID- 12222861
TI  - Laser interstitial thermotherapy (LITT) monitoring using high-resolution digital
      mammography: theory and experimental studies.
AB  - Laser interstitial thermotherapy (LITT) is a minimally-invasive laser
      hyperthermia procedure for the treatment of localized tumours. Real-time
      monitoring of LITT is essential to control the extent of tumour destruction and
      ensure safe and effective treatments. The feasibility of using high-resolution
      digital x-ray mammography to monitor LITT of breast cancer was evaluated. Tissue
      phantoms including polyacrylamide hydrogel and cadaver porcine tissue were heated
      using a 980 nm diode laser delivered through optical fibres with diffusing tips.
      Digital images of the tissue phantoms were recorded with a high-resolution
      digital stereotactic breast biopsy system during heating. The recorded images
      were processed and analysed to detect heat-induced changes. No changes were
      detected during heating of the hydrogel. Pixel-by-pixel subtraction of the
      initial image from images taken during laser heating shows observable thermally
      induced changes around the fibre during laser irradiation that correlate with the
      thermal denaturation zone observed by gross anatomy. These experiments
      demonstrate that high-resolution digital x-ray mammography can be used to detect
      heat-induced tissue changes during experimental LITT in fibro-fatty tissue.

PMID- 12222862
TI  - Dosimetric considerations for validation of a sequential IMRT process with a
      commercial treatment planning system.
AB  - Commercial multileaf collimator (MLC) systems can employ leaves with rounded
      ends. Treatment planning beam modelling should consider the effects of
      transmission through rounded leaf ends to provide accurate dosimetry for IMRT
      treatments delivered with segmented MLC. We determined that an MLC leaf gap
      reduction of 1.4 mm is required to obtain an agreement between calculated and
      measured profile 50% dose points. A head and neck dosimetry phantom, supplied by
      the Radiological Physics Center (RPC), was planned and irradiated as a necessary
      credentialing requirement for the RTOG H-0022 protocol. The agreement between the
      RPC TLD measurements and treatment planning calculations was within experimental
      error for the primary and secondary planning target volumes (PTVs); however, the
      calculated mean dose for the critical structure was approximately 9% lower than
      the RPC TLD measurements. RPC radiochromic film profile measurements also
      indicated significant discrepancies (>5%) with calculated values especially in
      the high dose gradient region in the vicinity of the critical structure. These
      results substantiate our own in-house phantom measurements, performed with the
      same IMRT fields as for the RPC phantom experiment, using Kodak EDR2 film to
      measure absolute dose. Our results indicate a maximum underestimate of calculated
      dose of 12% with no leaf gap reduction. The discrepancy between measured and
      calculated phantom values is reduced to +/- 5% when a leaf gap reduction of 1.4
      mm is used. A further improvement in the accuracy of dose calculation is not
      possible without a more accurate modelling of the leaf end transmission by the
      planning system. In the absence of published dosimetric criteria for IMRT our
      results stress the need for stringent in-house dosimetric QA and validation for
      IMRT treatments. We found the dosimetric validation service provided by the RPC
      to be a valuable component of our IMRT validation efforts.

PMID- 12222863
TI  - Irradiation characteristics of BNCT using near-threshold 7Li(p, n)7Be direct
      neutrons: application to intra-operative BNCT for malignant brain tumours.
AB  - A calculation method for the dosage of neutrons by near-threshold 7Li(p, n)7Be
      and gamma rays by 7Li(p, p'gamma)7Li was validated through experiments with
      variable distance between the Li target and the phantom, focusing on large
      angular dependence. The production of neutrons and gamma rays in the Li target
      was calculated by Lee's method and their transport in the phantom was calculated
      using the MCNP-4B code. The dosage in intra-operative boron neutron capture
      therapy (BNCT) using near-threshold 7Li(p, n)7Be direct neutrons was evaluated
      using the validated calculation method. The effectiveness of the usage of the
      direct neutrons was confirmed from the existence of the region satisfying the
      requirements of the protocol utilized in intra-operative BNCT for brain tumours
      in Japan. The boron-dose enhancer (BDE) introduced in this paper to increase the
      contribution of the 10B(n, alpha)7Li dose in the living body was effective. The
      void utilized to increase the dose in deep regions was also effective with BDE.
      For the investigation of 1.900 MeV proton beams, for example, it was found that
      intraoperative BNCT using near-threshold 7Li(p, n)7Be direct neutrons is
      feasible.

PMID- 12222864
TI  - The syed temporary interstitial iridium gynaecological implant: an inverse
      planning system.
AB  - Patients with advanced gynaecological cancer are often treated with a temporary
      interstitial implant using the Syed template and Ir- 192 ribbons at the Memorial
      Sloan-Kettering Cancer Center. Urgency in planning is great. We created a
      computerized inverse planning system for the Syed temporary gynaecological
      implant, which optimized the ribbon strengths a few seconds after catheter
      digitization. Inverse planning was achieved with simulated annealing. We
      discovered that hand-drawn target volumes had drawbacks; hence instead of
      producing a grid of points based on target volume, the optimization points were
      generated directly from the catheter positions without requiring an explicit
      target volume. Since all seeds in the same ribbon had the same strength, the
      minimum doses were located at both ends of the implant. Optimization points
      generated at both ends ensured coverage of the whole implant. Inverse planning
      took only a few seconds, and generated plans that provide a good starting point
      for manual improvement.

PMID- 12222865
TI  - Optimal needle arrangement for intraoperative planning in permanent I-125
      prostate implants.
AB  - One limitation of intraoperative planning of permanent prostate implants is that
      needles must already be in the gland before planning images are acquired.
      Improperly placed needles often restrict the capability of generating optimal
      seed placement. We developed guiding principles for the proper layout of needles
      within the treatment volume. The Memorial Sloan-Kettering Cancer Center planning
      system employs a genetic algorithm to find the optimal seed implantation pattern
      consistent with pre-assigned constraints (needle geometry, uniformity, conformity
      and the avoidance of high doses to urethra and rectum). Ultrasound volumes for
      twelve patients with 1-125 implants were used to generate six plans per patient
      (total 72 plans) with different needle arrangements. The plans were evaluated in
      terms of V100 (percentage prostate volume receiving at least the prescription
      dose), U135 (percentage urethra volume receiving at least 135% of prescription
      dose), and CI (conformity index, the ratio of treatment volume to prescription
      dose volume.) The method termed POSTCTR, in which needles were placed on the
      periphery of the largest ultrasound slice and posterior central needles were
      placed as needed, consistently gave superior results for all prostate sizes.
      Another arrangement, labelled POSTLAT, where the needles were placed peripherally
      with additional needles in the posterior lateral lobes, also gave satisfactory
      results. We advocate two needle arrangements, POSTCTR and POSTLAT, with the
      former giving better results.

PMID- 12222866
TI  - Chromosome structure and nuclear architecture: implications for gene therapy.
AB  - A reductionist view of mechanisms that control chromatin function might be
      appealing in its simplicity. It is tempting, for example, to view the process of
      gene expression as a series of simple protein-DNA and protein-protein
      interactions that lead, ultimately, to the assembly of an engaged transcription
      complex. RNA synthesis would then ensue to activate the pathway of gene
      expression. Yet attractive as this scheme may be, it is also clear that it bears
      only passing resemblance to events that occur in mammalian cells where a variety
      of epigenetic features might profoundly affect chromatin function. This review
      sets out to analyze our present knowledge of epigenetic features that influences
      chromatin function while placing particular emphasis on those features that are
      likely to impact on our ability to perform stable gene expression from ectopic
      genes - the major requirement of gene therapy.

PMID- 12222867
TI  - Extrachromosomal plasmid vectors for gene therapy.
AB  - Extrachromosomal DNA is becoming widely utilized as a gene therapy vector.
      Plasmid DNA offers multiple advantages over viral gene therapy vectors, including
      large packaging capacity, stability without integration and reduced toxicity.
      Furthermore, plasmid DNA can be delivered to many different tissues, using a
      variety of delivery techniques currently being developed. This review will
      discuss the advantages of extrachromosomal DNA as a gene therapy vector,
      highlighting recent advances and successes in its use in vivo.

PMID- 12222868
TI  - Use of adenovirus proteins to enhance the transfection activity of synthetic gene
      delivery systems.
AB  - This review focuses on the growing field of research concerned with the
      application of adenovirus proteins to improve the transfection efficiency of
      synthetic gene delivery systems. Several adenovirus component proteins influence
      cellular activity of the infecting adenovirus and the overall effect is a highly
      regulated and efficient infection pathway. It is possible that some of these
      proteins may be incorporated into synthetic gene delivery vectors, to Improve
      specific components of their cellular processing and improve transfection
      activity. Several adenovirus proteins have been introduced into synthetic vector
      systems. In particular, the penton base, which participates in cellular entry and
      endosomal escape of the adenovirus, shows an ability to increase cellular uptake
      and cytoplasmic penetration of synthetic systems. Similarly, hexon, the major
      adenovirus coat protein, is involved in the nuclear delivery of the infecting
      virus and can be exploited for enhancing nuclear targeting of synthetic systems.
      The possibility of using classical nuclear localization sequences from adenovirus
      proteins has also been evaluated. Finally, there is considerable interest in the
      use of adenovirus core proteins, such as mu, to improve properties of DNA
      condensation and unpackaging following the arrival of synthetic vectors in the
      nuclei of target cells.

PMID- 12222869
TI  - What can SV40-derived vectors do for gene therapy?
AB  - The limited success of gene therapy as an approach to treating human disease
      largely reflects the limitations of the gene delivery vectors that have been
      used. Poor titers, low transduction efficiency, waning transgene expression and
      immunogenicity have remained obstacles in the field. As a consequence, much
      research in normal, immunocompetent animals has not demonstrated therapeutic
      levels of gene delivery, and results from most human clinical trials have been
      predictably discouraging. Recombinant gene transfer vectors derived from SV40
      virus (rSV40) are potentially of great interest for those working in gene
      therapy, since these vectors are not subject to many of the problems that have
      limited gene delivery using other vector systems. rSV40 is made at a very high
      titer and infects - and so transduces - almost all nucleated cell types very
      efficiently, regardless of lineage or whether they are resting or dividing; they
      integrate and are not susceptible to transgene silencing; and they elicit no
      detectable immune response on the part of normal animals and so can be used to
      deliver multiple transgenes over time and in sequence. The recent development of
      'gutless' rSV40 vectors has expanded the range of potential therapeutic
      transgenes that can be delivered with this system and added flexibility to the
      expression configurations that can be accommodated. All of these functional
      characteristics of SV40-derived vectors have their bases in the biology of SV40
      and similar viruses, and have important implications for the potential utility of
      rSV40 vectors in gene therapeutics. Like all viral gene delivery systems, these
      vectors have their idiosyncrasies and limitations. They also allow gene delivery
      that bypasses many of the difficulties that have plagued the field from its
      inception.

PMID- 12222870
TI  - Safety features of retroviral vectors.
AB  - Although retroviral vectors based upon the murine leukemia virus have good safety
      records from clinical trials, attention to safety issues is crucial for the
      advancement of retroviral gene therapy. Key issues are to reduce uncontrolled
      transfer of viral or non-viral genetic information and to prevent the formation
      of replicating retroviruses. Safety features are also being incorporated into the
      novel attenuated lentiviral vectors that open new prospects for gene delivery.
      Here, we highlight features developed to restrict the transfer of viral genes,
      immobilize transfer vectors in target cells, or control interactions with other
      retroviruses in producer or target cells, as well as new developments in tissue
      targeted and regulated vectors.

PMID- 12222871
TI  - Fighting fire with fire: attacking the complexity of human tumors with armed
      therapeutic viruses.
AB  - Cancer gene therapies have centered on the use of a single gene, directed against
      a particular property or single aspect of tumor biology, to treat neoplastic
      disease. These therapies have met with limited clinical success. This is,
      perhaps, not surprising given the complex and heterogeneous nature of solid
      tumors. Treatments targeted at confronting multiple dimensions of human tumors
      are needed. Armed therapeutic viruses (oncolytic viruses carrying therapeutic
      genes) represent a system where the concerted action of multiple therapeutics can
      be joined into a single agent, and represent a promising avenue for developing
      future cancer therapies.

PMID- 12222872
TI  - The future of Duchenne muscular dystrophy gene therapy: shrinking the dystrophin
      gene.
AB  - Duchenne muscular dystrophy is a debilitating muscle-wasting disease caused by
      mutations in the dystrophin gene - one of the largest genes identified thus far -
      and which ultimately results in premature death. With no current treatment
      available, the hopes of many sufferers lie in the establishment of an effective
      gene therapy. The adeno-associated virus is now emerging as a premium gene
      transfer vector eliciting minimal immune response from the host and allowing for
      long-term gene expression. It is the scope of this review to examine the recent
      efforts that have been made to develop ultra-truncated versions of the dystrophin
      gene that retain functionality, yet can still be cloned into recombinant adeno
      associated viral vectors and other low-capacity vector systems.

PMID- 12222873
TI  - Gene therapy for the lysosomal storage disorders.
AB  - The lysosomal storage disorders (LSD) are monogenic inborn errors of metabolism
      with heterogeneous pathophysiology and clinical manifestations. In recent
      decades, these disorders have been models for the development of molecular and
      cellular therapies for inherited metabolic diseases. Studies in preclinical in
      vitro systems and animal models have established proof-of-concept for the
      development of bone marrow transplantation (BMT) and enzyme-replacement therapy
      (ERT) as therapeutic options for several LSDs. BMT is limited by poor donor
      availability and high morbidity and mortality, and although ERT is a good
      treatment, it is not a life-long cure. Its high cost remains an impediment for
      developing countries. While substrate synthesis inhibition therapy is an
      important idea, its clinical use is far from certain. The neuropathology present
      in many LSDs has responded poorly to BMT or ERT, which makes gene therapy an
      attractive therapeutic alternative. Oncoretroviral vectors, and more recently
      adeno-associated and lentiviral vectors have been tested with some success. This
      review summarizes the main gene therapy strategies which have been employed or
      are under development for both non-neurological and neuronopathic LSDs. Some of
      the in vitro and in vivo preclinical studies presented herein have provided the
      rationale for gene therapy clinical trials for Gaucher disease Type 1.

PMID- 12222874
TI  - Progress and challenges in viral vector-mediated gene transfer to the brain.
AB  - Gene transfer into the brain allows the manipulation of transgene expression in
      both time and space. Recently developed gene transfer technologies allow
      transgenes to be expressed in any anatomically, biochemically or functionally
      distinct group of brain cells. Gene transfer has been used to alter the
      expression of neurotransmitter receptors, ion channels, signaling proteins,
      neuronal growth, differentiation and survival factors, and thus to modify brain
      anatomy, neuron physiology, behavior and pathology. However, challenges remain in
      making gene therapy a more widespread tool for the treatment of neurological
      disease. We have identified the following as areas needing development: access
      and delivery of viral vectors to the brain; diffusion of viral vectors and
      transgenes throughout large areas of brain tissue; viral vector side effects and
      toxicity, inflammatory and immune responses to vectors; long-term stable
      transgene expression; cell type-specific expression of transgenes; and the
      ability of the experimenter or physician to switch transgene expression 'on' and
      'off' at will. In the last year, neuro-gene therapy has shown that brain defects
      in experimental disease models can be prevented and corrected, and that viral
      vectors and encoded transgenes can be made to diffuse over larger brain areas. In
      addition, the cause of vector-induced inflammation and immune responses have
      begun to be elucidated, so that rational approaches can be developed to avoid
      these complications. Further improvements in viral vectors will facilitate
      clinical trials in the near future.

PMID- 12222875
TI  - From the antigen-presenting cell to the antigen-presenting vesicle: the exosomes.
AB  - Exosomes are membrane vesicles of 30 to 100 nm in diameter, of endocytic origin,
      and are produced and secreted in vitro by living cells of diverse origin. In vivo
      and in vitro experiments suggest, from their particular proteomic composition,
      that exosomes are involved in the transfer of tumor antigens to antigen
      presenting cells, and in the stimulation of a specific immune response. In this
      review, we provide a molecular characterization of exosomes. The hypotheses
      accounting for exosome biogenesis will be outlined. Finally, we will describe
      their bioactivities and discuss their potential relevance and clinical
      implementation for cancer immunotherapy.

PMID- 12222876
TI  - Gene therapy and tissue engineering based on muscle-derived stem cells.
AB  - Skeletal muscle represents a convenient source of stem cells for cell-based
      tissue and genetic engineering. Muscle-derived stem cells (MDSCs) exhibit both
      multipotentiality and self-renewal capabilities, and are considered to be
      distinct from the well-studied satellite cell, another type of muscle stem cell
      that is capable of self-renewal and myogenic lineage differentiation. The MDSC
      appears to have less restricted differentiation capabilities as compared with the
      satellite cell, and may be a precursor of the satellite cell. This review
      considers the evidence for the existence of MDSCs as well as their origin. We
      will discuss recent investigations highlighting the potential of stem cell
      transplantation for the treatment of skeletal, cardiac and smooth muscle injuries
      and disease. We will highlight challenges in bridging the gap between
      understanding basic stem cell biology and clinical utilization for cell therapy.

PMID- 12222877
TI  - Cell-mediated gene therapy for bone formation and regeneration.
AB  - Cell-mediated gene therapy is one of the new modalities branching out from the
      wide-ranging field of gene transfer and therapy. When applied to bone formation
      and regeneration, it has particular advantages depending on the type of cell used
      as a platform for gene delivery. When utilizing adult mesenchymal stem cells or
      osteoprogenitor cells for the expression of bone-promoting osteogenic factors,
      the cells not only express the factors promoting bone growth, but can respond,
      differentiate and participate in the bone formation process. The ability of
      engineered cells to respond to the transgene, as well as to other local signals
      in vivo, confers on them special properties that enable the formation and
      regeneration of large-scale bone tissue. This approach is a paradigm for the
      development of gene therapy strategies for other skeletal tissues. Here, we
      review the most recent studies related to cell-mediated gene therapy for bone
      formation and regeneration.

PMID- 12222878
TI  - Bone marrow-derived endothelial progenitor cells for vascular regeneration.
AB  - It has recently been demonstrated that postnatal neovascularization is not
      restricted to angiogenesis, but also includes vasculogenesis. During adult
      vasculogenesis, bone marrow (BM)-derived endothelial progenitor cells (EPCs) are
      recruited to the systemic circulation in response to certain cytokines and/or
      tissue ischemia, and incorporate into sites of neovascularization. EPCs have also
      been investigated as therapeutic agents in a 'supply-side' approach to promoting
      neovascularization under pathological conditions. This review highlights the
      discovery of BM-derived EPCs and their therapeutic potential for vascular
      regeneration.

PMID- 12222879
TI  - Technology evaluation: DCVax, Northwest Biotherapeutics.
AB  - DCVax, a dendritic cell-based immunotherapy, is an active immunization platform
      being developed by Northwest Biotherapeutics for the potential treatment of
      multiple malignancies, including hormone-refractory metastatic prostate cancer,
      non-small-cell lung cancer, renal cancer and glioblastoma multiforme. The DCVax
      platform is tailored to a specific cancer type with either purified tumor
      specific antigen or tumor cell extracts derived from patients at the time of
      resection. Phase I/II clinical trials of DCVax-Prostate have been completed, and
      phase III clinical trials have recently been initiated. DCVax-Brain is currently
      undergoing phase II clinical trials, and DCVax-Lung recently received approval
      from the US FDA for phase I clinical trials.

PMID- 12222880
TI  - Impairment of sea urchin sperm quality by UV-B radiation: predicting
      fertilization success from sperm motility.
AB  - Sperm quality of the sea urchin, Anthocidaris crassispina, after exposure to
      environmentally realistic UV-B irradiances, was assessed by changes in sperm
      motility (measured by the computer-assisted sperm analysis (CASA) system), and
      related to subsequent fertilization success. Percentage motile sperm of A.
      crassispina declined significantly after exposure to a UV-B dose of 16.2 kJ m(
      2), while sperm motion velocity as measured by curvilinear velocity (VCL),
      straight line velocity (VSL), and average path velocity (VAP) showed significant
      reduction after exposure to a UV-B dose of 5.4 kJ m(-2). A parallel study showed
      that fertilization success was significantly reduced after sperm were exposed to
      UV-B doses > or = 5.4 kJ m(-2). Notably, the four sperm motility parameters were
      strongly correlated with fertilization success (P < 0.001), followed the
      increasing order: VSL (r = 0.8) < % motile sperm (r = 0.804) < VCL (r = 0.912) <
      VAP (r = 0.928). Fertilization success is best predicted by VAP using the
      exponential model: y = 8.678 + 90.202/[1 + exp(82.83 - x)/10.27)] (r(2) = 0.95).
      Thus, impairment of sperm motility of sea urchin, as measured by the CASA method,
      can be used to predict reproductive success and ecological effects.

PMID- 12222881
TI  - Tracing the source of 3,3'-dichlorobiphenyl found in samples collected in and
      around Halifax Harbour.
AB  - 3,3'-dichlorobiphenyl (IUPAC No. 11), a chlorobiphenyl (CB) that is not generally
      analysed in environmental studies of CBs, is found, sometimes at high
      concentrations, in water, suspended particulate material, biota and sediments
      from Halifax Harbour, NS, Canada. The results presented demonstrate the need for
      investigations of non-Aroclor CBs like CB 11. Not only can they have rather
      elevated environmental concentrations like those reported here for CB 11, but
      they also can be members of the more toxic non-ortho class of CBs and thus
      important from a toxicity standpoint. The focus of this paper was to investigate
      the possible sources of CB 11, a trace constituent of commercial mixtures, but
      dominant in various environmental compartments of Halifax Harbour.

PMID- 12222882
TI  - Occurrence and biological impacts of fishing gear and other marine debris in the
      Florida Keys.

PMID- 12222883
TI  - Environmental assessment of a large industrial marine complex based on a
      community of benthic filter-feeders.
AB  - Biological quality in a bay affected by man's activities was evaluated by means
      of the composition of assemblages of sponges and ascidians. Our results showed
      that the structure of these two groups of filter-feeders aided in discriminating
      between undisturbed and disturbed areas, establishing different "environmental
      health categories" from moderately to strongly disturbed areas, and in
      ascertaining the extension of the area of each "health category". We were able to
      divide the bay into four zones based on type of disturbance or anthropogenic
      source: (1) stations free of any source of disturbance, (2) stations under
      moderate disturbance, located close to industrial ports, millworks, etc., (3)
      stations that are under the direct influence of industrial wastes such as a power
      station and oil refinery, and (4) stations near strongly disturbed areas,
      influenced directly by harmful steelworks activities. We differentiated clearly
      between four large species assemblages, and related the composition of these
      assemblages to different kinds of disturbances. Thus, these species could be used
      to manage the marine environment in this bay by comparing the observed fauna,
      with expected fauna in an unstressed site. Moreover, the joint presence of the
      sponge Cliona vastifica and tunicate Policitor adriaticum seems always to
      indicate a more or less pristine environmental situation, functioning as
      bioindicators of normal conditions. We think that the use of specific
      bioindicators for monitoring disturbance is a valid tool to establish baselines
      to predict impacts associated with industrial development in many marine
      ecosystems. The advantages to monitoring communities on hard rocks versus sandy
      or muddy bottoms are also commented upon.

PMID- 12222884
TI  - Assessing the trophic state and eutrophication of coastal marine systems: a new
      approach based on the biochemical composition of sediment organic matter.
AB  - We used a biochemical approach based on the analysis of the quality and quantity
      of sedimentary organic matter for identifying new descriptors of the trophic
      state and environmental quality of coastal marine systems. A large-scale study,
      including 99 stations, belonging to 33 transects, was carried out along 250 km of
      the Apulian coasts (Mediterranean Sea) in March and September 2000. The
      investigated area covered a wide range of anthropogenic impacts (industrial
      ports, tourist harbours, areas affected by power plants and industrial wastes,
      mariculture areas). Other sites, including marine protected areas (i.e., without
      any apparent impact), were used as "control". Water column and benthic parameters
      provided different indications and classifications of the trophic state of
      coastal marine systems. We found that phytopigment content of the sediments
      changed in response to all different sources of anthropogenic impact and resulted
      in a useful descriptor of the trophic state and environmental quality. Highest
      sediment chlorophyll-a concentrations, indicating conditions of increasing
      eutrophication, were found in areas impacted by the discharge of heated waters
      from a power plant. In particular, the contribution of the autotrophic biomass to
      the biopolymeric carbon pool appeared to be a good descriptor of the decreasing
      environmental quality. Independently from the sampling period or the pollution
      source such contribution was significantly lower in transects subjected to
      anthropogenic impact than in control areas. Differences in trophic conditions
      were evident both in terms of quantity (i.e., total organic matter content) and
      quality (i.e., biochemical composition) of sediment organic matter. In
      particular, sediment protein concentration appeared to be a good descriptor of
      the trophic state of the benthic systems at different spatial scales.
      Multivariate (MDS) analysis allowed identifying areas characterised by
      hypertrophic, eutrophic and meso-oligotrophic conditions and to define relative
      threshold levels. A classification of the trophic state of coastal systems based
      on protein and carbohydrate concentrations is proposed.

PMID- 12222885
TI  - Inhibition of coral photosynthesis by the antifouling herbicide Irgarol 1051.
AB  - International regulation of organotin compounds for use in antifouling paints has
      led to the development and increased use of replacement compounds, notably the s
      triazine herbicide Irgarol 1051. Little is known about the distribution of
      Irgarol 1051 in tropical waters. Nor has the potential impact of this triazine
      upon photosynthesis of endosymbiotic microalgae (zooxanthellae) in corals been
      assessed. In this study Irgarol 1051 was detected in marinas, harbours and
      coastal waters of the Florida Keys, Bermuda and St. Croix, with concentrations
      ranging between 3 and 294 ng 1(-1). 14C incubation experiments with isolated
      zooxanthellae from the common inshore coral Madracis mirabilis showed no
      incorporation of H14CO3- from the sea water medium after 4-8 h exposure to
      Irgarol 1051 concentrations as low as 63 ng 1(-1). Reduction in net
      photosynthesis of intact corals was found at concentrations of l00 ng 1(-1) with
      little or no photosynthesis at concentrations exceeding 1000 ng 1(-1) after 2-8 h
      exposure at all irradiances. The data suggest Irgarol 1051 to be both prevalent
      in tropical marine ecosystems and a potent inhibitor of coral photosynthesis at
      environmentally relevant concentrations.

PMID- 12222886
TI  - Environmental pollution in the Gulf of Guinea--a regional approach.
AB  - Environmental pollution in the Gulf of Guinea (GOG) coastal zone has caused
      eutrophication and oxygen depletion in the lagoon systems, particularly around
      the urban centres, resulting in decreased fish (reproduction) levels and
      waterborne diseases. A pollution sources assessment was undertaken by six
      countries in the region as a first step in defining a region-wide Environmental
      Management Plan. Results show that households produce 90% of solid waste.
      Industry, however, is responsible for substantial amounts of hazardous waste,
      specifically the Nigerian petroleum industry. The latter is also responsible for
      the spilling of large amounts of oil. BOD load from industrial effluents is
      slightly larger than domestic loads in the industrialised coastal zone.
      Wastewater treatment systems are either absent or inadequate. Apart from large
      scale gas flaring in Nigeria, air pollution, in terms of COx, HC, NOx and SO2
      emissions, is contributed mainly by traffic. Particulates, originate mainly from
      industries and domestic biomass burning.

PMID- 12222887
TI  - Concentrations of PCBs in coastal mangrove sediments of Hong Kong.
AB  - The concentrations of polychlorinated biphenyls (PCBs) in surface sediments of
      ten mangrove sites in Hong Kong were determined by Congener-specific and Arcolor
      methods. Spatial variations were found between mangrove sites and within the same
      site, indicating that the sediment samples were heterogeneous and total PCBs
      concentrations in mangrove sediments should be normalised to compensate for
      natural variability and for identifying serious anthropogenic contamination. In
      addition to total organic carbon, Al, Fe and Mn were possible normalisers. Based
      on PCB/normaliser ratio and 95% prediction limits of scatter plots between total
      PCB and normaliser, all mangrove sites were not seriously contaminated by human
      activities. The estimated total PCBs concentrations (quantified by Congener
      specific method) for most sediment ranged from 0.5 to 5.8 ng g(-1) (dry weight, n
      = 92). However, very high concentrations of PCB were found in sub-samples from Yi
      O, Tolo Pond and Lai Chi Wo, suggesting that these samples represented the PCB
      contaminated "hot spots".

PMID- 12222888
TI  - Re-colonisation and recovery of populations of dogwhelks Nucella lapillus (L.) on
      shores formerly subject to severe TBT contamination.
AB  - Dogwhelks Nucella lapillus became locally extinct on some shores adjacent to
      areas of high shipping/boating activity during the period of high tributyltin
      (TBT) contamination in the 1980s and early 1990s. However, the species has now re
      colonised sites at which extinction occurred on the Isle of Cumbrae, the
      northeast coast of England, the Shetland Isles and southwest England. There have
      also been substantial declines in the severity of imposex on adjacent shores
      where the species has persisted during this period. Re-colonisation and recovery
      can be attributed to two measures: regulations prohibiting the use of TBT-based
      paints on vessels < 25 m in length and the development of slow-releasing, self
      polishing copolymer paints. Nevertheless, the International Maritime Organisation
      has now imposed a total ban on the use of TBT-based paints as antifoulants. This
      is almost certain to result in the use of paints containing alternative biocides
      and there is widespread concern that there is relatively little information on
      which to assess their likely environmental impacts. They could cause substantial
      environmental damage.

PMID- 12222889
TI  - 239+240Pu and 137Cs concentrations for zooplankton and nekton in the Northwest
      Pacific and Antarctic Oceans (1993-1996).
AB  - The concentrations of 239+240Pu and 137Cs in zooplankton and nekton in the
      Northwest Pacific and Southern Oceans were measured during the period 1993-1996.
      The object of the sampling was to assess the potential impacts of existing
      submerged anthropogenic-radioactive materials in the western North Pacific as
      well as the East China Sea. Samples from the Bransfield Strait of the Antarctic
      Ocean provided a control source impacted by only atmospheric bomb fallout. No
      particularly elevated levels of 239+240Pu were found in zooplankton samples from
      the Northwest Pacific, although significantly lower levels of 239+240Pu were
      found in three mixed zooplankton samples from the Bransfield Strait. The body
      burden of 239+240Pu in zooplankton appears to reflect concentrations in ambient
      seawater with some variation. Some additional measurements of 137Cs in fish are
      also reported here to complement existing databases and for future reference in
      the regional marine environmental radioactivity monitoring effort.

PMID- 12222890
TI  - Preliminary evidence for human fecal contamination in corals of the Florida Keys,
      USA.
AB  - Corals and reef environments are under increased stress from anthropogenic
      activities, particularly those in the vicinity of heavily populated areas such as
      the Florida Keys. The potential adverse impacts of wastewater can affect both the
      environment and human health; however, because of the high decay rate of
      bacterial indicators in coral reef waters it has been difficult to document the
      presence of microbial contaminants and to assign risks in these environments.
      Here we show initial evidence that microorganisms associated with human feces are
      concentrated along the surface of coral heads relative to the overlying water
      column in the Florida Keys. Bacterial indicators (fecal coliform bacteria,
      enterococci or Clostridium perfringens) were detected in 66.7% of the coral
      surface microlayer (CSM) samples at levels between five and 1000 CFU/100 ml, but
      were found infrequently and at low numbers in the overlying water column ( < or =
      2.5 CFU/100 ml). Similarly, enterovirus nucleic acid sequences, an indicator of
      human-specific waste, were detected in 93.3% of the CSM samples and only once in
      the water column by cell culture. Results show that coral mucus may accumulate
      enteric microorganisms in reef environments, and may indicate a risk to public
      and environmental health despite low indicator levels in the surrounding water.

PMID- 12222891
TI  - Genetic diversity and metal tolerance of two marine species: a comparison between
      populations from contaminated and reference sites.
AB  - Long-term contamination of the marine environment surrounding a lead smelter
      offered a unique opportunity to examine how pollutants might have acted to alter
      genetic characteristics of populations of organisms in the receiving system. This
      study used random amplified polymorphic DNA analysis to compare the genetic
      diversity of populations of the prawn, Leander intermedius, and the isopod,
      Platynympha longicaudata from the smelter discharge site with reference
      populations. The genetic diversity of the prawn population from the smelter
      discharge site (Port Pirie) was lower than that found in one reference
      population, and not significantly different from the other two reference
      populations. Genetic diversity of the Port Pirie population of isopods was found
      to be significantly lower than that of all reference populations. Prawns and
      isopods were also exposed to metal mixtures in the laboratory in a similar ratio
      to that found in seston near the smelter effluent discharge site. Both pre
      exposed and reference populations of prawns tolerated elevated levels of metals
      and exhibited no significant difference in response. This contrasted with the
      isopods, with the pre-exposed isopod population showing greater tolerance to
      elevated metal levels compared with the reference population. These results
      highlight the need to include a number of reference populations for comparative
      purposes in genetic diversity studies, and the need to assess the influence of
      pollution on the genetic diversity of more than one species if genetic diversity
      analyses are to be used to gauge remediation success.

PMID- 12222892
TI  - The effect of an oil drilling operation on the trace metal concentrations in
      offshore bottom sediments of the Campos Basin oil field, SE Brazil.
AB  - The concentrations of Al, Fe, Mn, Zn, Cu, Pb, Ni, Cr, Ba, V, Sn and As in
      offshore bottom sediments from the Bacia de Campos oil field, SE Brazil, were
      measured at the beginning and at 7 months after completion of the drilling
      operation. Concentrations of Al, Fe, Ba, Cr, Ni and Zn were significantly higher
      closer to the drilling site compared to stations far from the site. Average
      concentrations of Al, Cu, and in particular of Ni, were significantly higher at
      the end of the drilling operation than at the beginning. Comparison between
      drilling area sediments with control sediments of the continental platform,
      however, showed no significant difference in trace metal concentrations. Under
      the operation conditions of this drilling event, the results show that while
      changes in some trace metal concentrations do occur during drilling operations,
      they are not significantly large to be distinguished from natural variability of
      the local background concentrations.

PMID- 12222893
TI  - Impacts of milkfish (Chanos chanos) aquaculture on carbon and nutrient fluxes in
      the Bolinao area, Philippines.
AB  - Sediment oxygen consumption, TCO2 production and nutrient fluxes across the
      sediment-water interface were measured in sediments within and along a transect
      from four fish pens with production of milkfish (Chanos chanos) in the Bolinao
      area, The Philippines. The four fish pens were each representing a specific
      period in the production cycling. There was a positive linear relationship
      between the rates of sedimentation inside the fish pens and the sediment oxygen
      consumption indicating that the benthic processes were controlled by the input of
      organic matter from fish production. The nutrient fluxes were generally higher
      inside the fish pens, and nitrate was taken up (1.7-5.8 mmol m(-2) d(-1)) whereas
      ammonium (1-22 mmol m(-2) d(-1)) and phosphate (0.2-4.7 mmol m(-2) d(-1)) were
      released from the sediments. The sediments were enriched in organic matter with
      up to a factor 4 compared to outside. A mass balance for one crop of milkfish was
      constructed based on production data and on measured fluxes of nutrients in the
      fish pens to assess the loss of carbon and nutrients to the environment. There
      was a loss to the surroundings of carbon and nitrogen of 51-68% of the total
      input, whereas phosphorus was buried in the sediments inside the fish pens which
      acted as net sinks of phosphorus. The results obtained suggest that fish pen
      culture as practiced in the Bolinao area, leads to even greater impacts on
      benthic carbon and nutrient cycling than those found in suspended cage cultures.

PMID- 12222894
TI  - Organotin and Irgarol-1051 contamination in Singapore coastal waters.
AB  - The seas surrounding Singapore are principally utilized by the shipping industry
      but are now also increasingly used for a variety of other purposes, including
      desalination for supplies of drinking water and intensive aquaculture of food
      fish. While stringent environmental pollution standards are in place for
      industrial effluents, there is currently no legislative control over pollution
      from anti-fouling paints in Singapore. In this study, the concentrations of toxic
      antifouling agents tributyltin (TBT), triphenyltin (TPhT) and Irgarol-1051 (2
      methylthio-4-tert-butylamino-6-cyclopropylamino-s-triazine) were determined from
      seawater obtained from 26 locations along and off the coast of Singapore in
      October and November 2000. These compounds were isolated by liquid-liquid
      extraction derivatized under controlled microwave heating and quantified by gas
      chromatography-mass spectrometry. TBT concentrations in seawater ranged between
      0.43 and 3.20 microg 1(-1) with a mean value of 1.40 +/- 0.60 micro 1(-1). The
      mean values of DBT and MBT were 1.07 +/- 0.80 microg 11(-1) and 0.34 +/- 0.50
      microg 1(-1) respectively, while TPhT concentrations of up to 0.40 microg 1(-1)
      were found. Monophenyltin and diphenyltin were not detected in all samples
      analysed. Irgarol-1051 was found to be present at concentrations of between 3.02
      microg 1(-1) and 4.20 microg 1(-1) in seawater with a mean value of 2.00 +/- 1.20
      microg 1(-1).

PMID- 12222895
TI  - Baseline metal concentrations in sediments and fish, and the determination of
      bioindicators in the subtropical Chi-ku Lagoon, S W Taiwan.

PMID- 12222896
TI  - Whaling and whale conservation.

PMID- 12222897
TI  - Importance of consent.

PMID- 12222898
TI  - Practitioner biopsy services.

PMID- 12222899
TI  - Dental health education.

PMID- 12222900
TI  - ARF increase.

PMID- 12222901
TI  - Implant treatment.

PMID- 12222902
TI  - Deep carious lesions.

PMID- 12222903
TI  - Dental health education.

PMID- 12222904
TI  - Wilfred Fish lecture.
AB  - It is a great honour to be invited to deliver this lecture in memory of Sir
      Wilfred Fish, first President of the General Dental Council. I am only too well
      aware of my unfitness for the task: my experience of dentistry is limited to the
      dental chair; my knowledge of dental law is virtually nil. I trust that Sir
      Wilfred would not disapprove. His contribution to dentistry was enormous; his
      labours ensured that dentistry received both the independent recognition it
      merits and its own regulatory framework, freed from any sort of subservience to
      medicine.

PMID- 12222905
TI  - Disability part 1: the disability discrimination act (1995)--implications for
      dentists.
AB  - The Disability Discrimination Act (1995) (DDA) aims to end the discrimination
      which many disabled people face in their day-to-day lives. (1) But how many
      dentists are aware of their responsibilities under this Act? Dentists are already
      bound by Parts I and II of the DDA, but Part III, which is due to come into
      effect in 2004, and which is concerned with physical alterations to premises, has
      potentially profound implications for many in dental practice. Health Authorities
      in Merseyside, in the North West of England have been exploring ways in which
      access to dental care for disabled people can be improved. In this paper, the
      first of a series of three, we outline the DDA and how it affects dentists in
      general practice.

PMID- 12222906
TI  - Lingual nerve injury subsequent to wisdom teeth removal--a 5-year retrospective
      audit from a high street dental practice.
AB  - Lingual nerve damage subsequent to lower wisdom tooth removal affects a small
      number of patients, sometimes producing permanent sensory loss or impairment. A
      number of surgical techniques have been described which are associated with low
      incidences of this distressing post-operative complication. When a technique is
      adopted by an individual clinician then a personal audit may be prudent to
      establish how effective it is in relation to established nerve injury rates. This
      audit looks at a technique involving the minimal interference of lingual soft
      tissues during lower wisdom tooth removal in a high street practice situation for
      patients having mild to moderate impacted wisdom teeth removed under local
      anaesthetic. It was concluded that the technique employed was associated with a
      low incidence of lingual nerve trauma, comparable with that reported elsewhere.

PMID- 12222907
TI  - Regulating dental nursing in the UK.
AB  - There has been much discussion about the impending legislation for compulsory
      registration of dental nurses. A questionnaire survey of Oxfordshire dental
      practices found that 60% (153/254) of dental nurses had no formal qualifications.
      Of these 49% (75/153) were already on a training course or planning to apply for
      one although those who achieve mediated entry may discontinue training. Overall,
      40% (62/153) were planning to apply for mediated entry. Previous research
      indicates that there may be similarly high proportions of unqualified dental
      nurses throughout the UK. There are concerns that a rigid training programme and
      compulsory examinations will compound existing recruitment problems, and create a
      national shortfall of dental nurses. Proponents believe that formal training will
      better equip dental nurses to handle the demands of modern dental practice and
      bring them in line with other auxiliary health personnel. Training needs to be co
      ordinated nationally to ensure adequate access and consistent standards. Dental
      nurses and practices should be consulted and supported throughout the
      implementation period.

PMID- 12222908
TI  - Unintentional overdose of analgesia secondary to acute dental pain.
AB  - Three cases of unintentional overdose with simple analgesics are presented. Over
      a two month period, these patients presented to the accident and emergency (A&E)
      department with acute dental pain, outside normal working hours, having been
      unable to access emergency dental care. In one case the patient's reason for
      attendance was to obtain further supplies of analgesics. The patients required
      admission for assessment of the severity of the overdose in addition to advice
      about appropriate use of analgesics and advice on access to dental care. None of
      the patients required treatment for the overdose. These cases serve as a timely
      reminder of the importance of taking an accurate drug history in emergency
      situations. They also raise issues of patient education for self medication and
      access to emergency dental services outside normal working hours.

PMID- 12222909
TI  - Informed consent: optimism versus reality.
AB  - OBJECTIVE: To determine whether parents of children attending the outpatient
      general anaesthesia (OPGA) session at the Eastman Dental Hospital, London fully
      understand the proposed treatment. DESIGN: Observational study supported by
      structured questionnaires and interviews. SETTING: Casualty service in the
      Department of Paediatric Dentistry and the Victor Goldman Unit (a day-stay
      general anaesthetic unit) of the Eastman Dental Hospital. MAIN OUTCOME MEASURES:
      The parents' understanding of the consent was assessed based on their knowledge
      of the actual treatment procedure, the type of anaesthesia to be used and the
      number and type of teeth that would be extracted. RESULTS: Fifty-two of the 70
      subjects (74%) approached completed both parts of the survey (interviews one and
      two). Results showed that 40% of the written consent obtained from the parents
      were not valid. The subjects' knowledge of the proposed treatment improved on the
      day of the actual treatment although 19% of them still did not fully understand
      the procedure. There was a statistically significant increase in the proportion
      of valid consent on the day of the actual treatment. Many of the subjects had no
      knowledge of the type of anaesthesia that would be used for their children but
      were more aware of the number and type of teeth that were going to be extracted.
      The time interval between the consent process and the actual treatment did not
      have any significant effect on the subjects' understanding of the consent, but it
      implied that with time the subjects' knowledge improved. CONCLUSION: A proportion
      of subjects did not fully understand the proposed treatment procedure even after
      being adequately informed. Appropriate measures should be taken to ensure that
      the patients or their guardians truly understand the proposed treatment.

PMID- 12222910
TI  - A comparison of the index of complexity outcome and need (ICON) with the peer
      assessment rating (PAR) and the index of orthodontic treatment need (IOTN).
AB  - AIM: To evaluate any relationship between ICON, IOTN and PAR. To establish
      whether or not ICON could replace these indices as a measure of orthodontic
      treatment complexity, outcome and need. METHOD: The study models of 55
      consecutively treated cases were examined and PAR, IOTN and ICON recorded.
      RESULTS: The study showed significant correlations between IOTN and ICON with
      respect to need and PAR and ICON with respect to outcome. CONCLUSION: It appears
      that ICON does reflect UK opinion and the current study provides some evidence
      that ICON may effectively replace PAR and IOTN as a means of determining need and
      outcome.

PMID- 12222911
TI  - Gangrene secondary to axial torsion in a patient with Meckel's diverticulum.
AB  - This report discusses the case of a 35-year-old woman who was diagnosed with
      acute abdomen. The laparatomy revealed gangrene of Meckel's diverticulum
      secondary to its axial torsion. Resection of the diverticulum and primary end-to
      end anastomosis were performed. There were no problems during the postoperative
      period.

PMID- 12222912
TI  - Long-term results after cholecystectomy alone for patients with
      pancreaticobiliary maljunction without bile duct dilatation.
AB  - A pancreaticobiliary maljunction (PB-MJ) without bile duct dilatation is
      relatively rare. The standard treatment for these patients remains controversial.
      In this study, we followed up the patients with PB-MJ without bile duct
      dilatation who mainly underwent a cholecystectomy alone. Eighteen adult patients
      with PB-MJ without bile duct dilatation (8 males and 10 females with a mean age
      of 54.8 years) were treated surgically. When the diameter of the common bile duct
      was less than 10 mm, such bile ducts were diagnosed to have no dilatation. The
      main clinical indications for surgery were cholecystolithiasis in 12 patients,
      choledocholithiasis in 3, cholecystocholedocholithiasis in 1, and carcinoma of
      the gallbladder in 2. The amylase levels of gallbladder bile in 14 patients
      ranged from 115 to 454,000 IU/ml. A simple cholecystectomy was performed in 12
      patients, a cholecystectomy with bile duct drainage was performed in 3, a
      cholecystectomy with a choledochojejunostomy without bile duct resection was
      performed in 1, and a cholecystectomy with a lymph node dissection was performed
      in 2. Three patients died of other diseases. The remaining 15 patients have all
      been doing well for 20-209 months after surgery. In conclusion, a prophylactic
      resection of the extrahepatic bile duct and biliary diversion could be
      unnecessary for patients with PB-MJ without bile duct dilatation, when no bile
      stasis, such as choledocholithiasis, is observed.

PMID- 12222913
TI  - Management of tracheobronchial strictures and fistulas: a report and review of
      literature.
AB  - The treatment of tracheobronchial (TB) strictures and fistulas is an exceedingly
      difficult problem; therefore, the management needs to be individualized. The
      recent development and use of self-expanding endotracheal and bronchial stents
      have allowed for the successful management of many of these clinical entities.
      Such expandable metallic stents have provided definite advantages over solid
      stents by potentially offering a suitable long-term treatment for patients with
      neoplastic airway obstruction and fistulas. The silicone stents, which can be
      easily removed, are useful in instances requiring short-term relief. In the case
      of lung transplantation, a continued major source of concern is the prevalence of
      anastomotic complications secondary to impaired healing. Use of silicon, balloon
      expandable, and self-expandable wire stents has allowed for the successful
      management of this complex patient population. An aggressive surgical approach to
      resect stricture or fistula with benign etiology may still be warranted for those
      that are fit for such procedures.

PMID- 12222914
TI  - Delayed presentation of splenic injury: still a common syndrome.
AB  - The entity of delayed splenic rupture represents an initially missed injury, a
      delayed presentation of the latter, or an actually delayed development of an
      initially latent, minor, splenic injury. Having encountered a number of patients
      presenting with splenic rupture days after what was considered a minor abdominal
      trauma we review our experience with this entity. This is a retrospective study.
      During the past 6 years 26 patients were treated at our level II trauma center
      for blunt splenic injuries. The 8 patients who presented 48 h or more after
      injury are the focus of this communication. All patients had an underlying
      medical condition: five were drug addicts (one was HIV positive) and the other
      three were affected by cirrhosis, sickle cell disease, and HIV. The mechanisms of
      injury were as follows: blunt assault in 5 patients, a fall in 2 patients, and
      unknown in 1 patient. The patients presented to our hospital after a mean lag
      time of 5 days after injury (range, 2-10 days). One patient presented in shock
      and underwent laparotomy after a positive diagnostic peritoneal lavage. Four
      presented with a clinical acute abdomen, and three presented with abdominal pain
      and anemia. Abdominal computed tomography (CT) was performed in the seven
      hemodynamically stable patients demonstrating hemoperitoneum in all: five had a
      grade III injury and two had a grade II injury. All patients survived after an
      emergency splenectomy. Delayed presentation of splenic injury after minor
      abdominal trauma is not uncommon in our indigenous population. It may be
      associated with drug abuse and HIV.

PMID- 12222915
TI  - Adenosquamous carcinoma of the liver: clinicopathologic features in 12 patients
      and review of the literature.
AB  - We present and compare the clinical features and outcomes of 12 patients with
      primary adenosquamous carcinoma (ADS-CCC) of the liver who underwent hepatic
      resection at our institution with those of 29 cases whose surgical treatment were
      reported in the literature. Peripheral cholangiocarcinoma (CCC) occurs less
      frequently than hepatocellular carcinoma in most parts of the world. Reports of
      surgically treated cases of ADS-CCC are seen only sporadically because of the low
      resectability rate, difficulty in making an early diagnosis, and the poor
      prognosis. Furthermore, a clinicopathological study based on a certain number of
      surgically treated cases is still lacking. From 1977 to 2001, 12 cases of hepatic
      ADS-CCC who underwent hepatic resection were reviewed in respect to clinical
      features and long-term results. The clinical features and outcomes of the 29
      patients who underwent hepatic resection reported in the literature are also
      summarized for comparison. Of 228 surgically treated CCC patients in our
      institute, 12 (5.3%) were ADS-CCC. A male predominance was observed in our study
      and in the reported cases. In our series, prominent body weight loss and
      prominent relationship to hepatolithiasis were observed. The prognosis is dismal
      in patients with ADS-CCC who undergo hepatic resection; however, there was no
      significant difference in overall survival between the ADS-CCC and CCC groups. In
      our series, the 1-, 2-, and 3-year survival rates of ADS-CCC and CCC patients
      were 18.8%, 0%, and 0% and 32.8%, 14.8%, and 9.5%, respectively. ADS-CCC is
      prominently related to body weight loss and hepatolithiasis in our series
      compared with the reported cases. The prognosis of patients with ADS-CCC who
      undergo hepatic resection is dismal because of the specific biological behavior
      of ADS-CCC.

PMID- 12222916
TI  - Evaluation of clinicopathological factors and the correlation between the
      adhesion molecule CD44 variant 9 expression and pulmonary metastases from
      colorectal cancers.
AB  - Pulmonary metastases occur in 3% to 8% of all cases of colorectal cancers.
      Therefore, we evaluated prognostic factors and examined the correlation between
      the expression of adhesion molecule CD44 variant 9 and the pulmonary metastasis
      from colorectal cancer. Of 512 patients with colorectal cancers,
      clinicopathological findings, prognoses, and prognostic factors were evaluated in
      42 patients with pulmonary metastases (8%), together with the expression of
      adhesion molecule CD44 variant 9 by immunohistochemical staining with monoclonal
      antibody prepared in our department. It was found that the presence or absence of
      extrapulmonary metastasis, treatment by pulmonary resection, and serum
      carcinoembryonic antigen levels were prognostic factors. The 5-year survival rate
      was 35% in patients who underwent pulmonary resection. In addition, adhesion
      molecule CD44 variant 9 was expressed in the primary colorectal cancers in 89
      (42%) of 213 patients without hematogenous metastases and 23 (88%) of 26 patients
      with pulmonary metastases. Therefore, the rate of CD44 variant 9 expression in
      the primary colorectal cancer tissues was significantly higher in patients with
      pulmonary metastases from colorectal cancers. Among patients with pulmonary
      metastases from colorectal cancers, long-term survival was achieved in those
      without extrapulmonary metastases, because metastatic tumors in the lungs were
      completely removed by pulmonary resection. In addition, the abnormal expression
      of adhesion molecule CD44 variant 9 in the primary colorectal cancer is partly
      responsible for pulmonary metastasis.

PMID- 12222917
TI  - Retroperitoneal perforation of the appendix presenting as right thigh abscess.
AB  - A case of retroperitoneal perforation of the appendix presenting with a thigh
      abscess is described. The patient presented with pyrexia (38 degrees C) and
      abdominal and right thigh pain. There was tenderness in the right loin. His white
      blood cell count was 22 x 10(9)/L. An intravenous urogram revealed tapering of
      the right ureter at the L2/L3 level and suggested an infected obstructive
      uropathy. The patient failed to respond to drainage and antibiotics, so we
      performed a computed tomography scan, which showed a retroperitoneal abscess
      extending to the gluteal region and thigh, with signs of small bowel obstruction.
      This precipitated surgery. The route of extension of infection was through the
      sacrosciatic notch, which is considered to be a rare way of spread. The patient
      made a slow but eventual recovery. The overall mortality of this condition is
      high, but early recognition of an abdominal source of sepsis with appropriate
      treatment can improve survival.

PMID- 12222918
TI  - Mirizzi syndrome: a case report and review of the literature.
AB  - The Mirizzi syndrome is a rare benign cause of obstructive jaundice. The syndrome
      is a result of the impaction of a large stone, or several smaller ones, in either
      the Hartmann's pouch or the cystic duct, causing obstruction to the common
      hepatic duct. It is particularly interesting to surgeons because the surgery has
      to be carefully planned to avoid unnecessary damage to the common bile duct.
      Furthermore, it poses a differential diagnosis dilemma for surgeons as well as
      radiologists because there are no diagnostic procedures or clinical features that
      have a 100% specificity and sensitivity. As a result, the Mirizzi syndrome often
      has been mistaken for carcinoma of the gallbladder. We report one case of Mirizzi
      syndrome to draw attention to the importance of this syndrome and to describe the
      clinical, diagnostic, and therapeutic aspects of the disease.

PMID- 12222919
TI  - Unilateral progressive multiple sclerosing hemangioma in a young female
      successfully treated by pneumonectomy: report of a case.
AB  - A 25-year-old woman had been followed for 7 years after multiple pulmonary
      nodules were detected in both the upper and lower lobes of the left lung on chest
      X-ray when she was 17 years of age. These pulmonary nodules were gradually
      increasing in size and, at 25 years of age, transbronchofiberscopic biopsy
      suggested the possibility of adenocarcinoma. Left pneumonectomy was performed.
      The diagnosis of multiple tumors was confirmed as sclerosing hemangioma by
      postoperative histopathological examination of the resected lung. The patient has
      remained well for 2 years to date after resection.

PMID- 12222921
TI  - Spontaneous common bile duct perforation in adult: a case report and review.
AB  - Common bile duct perforation has been reported in adults after invasive
      procedures. Spontaneous common bile duct perforation is a rare entity as a cause
      of acute abdomen in adults. A few cases due to choledocholithiasis have been
      reported as a cause of spontaneous perforation. We report an adult patient who
      presented with acute abdomen after spontaneous common bile duct perforation due
      to unknown etiology who was treated successfully.

PMID- 12222920
TI  - Tracheobronchial tumor resection.
AB  - Primary tracheobronchial nonbronchogenic carcinoma tumors are uncommon. The
      presence of these tumors may cause asthmatic-like symptoms and marked respiratory
      distress. When seen, the patients are usually very apprehensive and present
      difficult decisions regarding treatment and surgery, especially with regard to
      anesthetic considerations. We are reporting our experience with these tumors in
      the community hospital. A number of patients are presented, including 1) a
      tracheal tumor during pregnancy, 2) a tracheobronchial tumor cast, and 3) a
      carinal resection. All resected patients did well with long-term survival.

PMID- 12222922
TI  - Endovascular repair of aortojejunal fistula.
AB  - A 64-year-old male with vascular occlusive disease involving multiple vessels is
      presented with a history of aortobifemoral bypass grafting and bilateral femoral
      false aneurysm surgery. More recently, he had cystectomy for bladder carcinoma
      and repeated urinary stents and sepsis. Gastrointestinal bleeding developed due
      to the aortic graft anastomotic false aneurysm eroding into the distal jejunum.
      Endograft placement stabilized the critical situation and served as a bridge to a
      safer, more elective resection of the previous graft, the false aneurysm, and the
      endograft with closure of the jejunum.

PMID- 12222924
TI  - Pericholecystic fistula: a study of 64 cases.
AB  - Spontaneous biliary fistulas are found quite often. Although previously
      considered as a contraindication to laparoscopic surgery, they are now being
      treated laparoscopically with all its advantages. Of 8015 patients undergoing
      laparoscopic cholecystectomy, 64 patients were diagnosed preoperatively;
      conversion to open surgery was required in 8 patients. The highest incidence of
      pericholecystic fistulas was found in the >60-year age group. The postoperative
      stay ranged from 3 to 8 days. All the patients were well at follow up.
      Laparoscopic management of pericholecystic fistulas is possible with low
      morbidity and no mortality.

PMID- 12222923
TI  - Torsion of the gallbladder in an adult: a rare case of acute cholecystitis.
AB  - Torsion of the gallbladder is a rare condition that is generally due to an
      abnormal anatomical variation, i.e., the presence of a long mesocyst with loss of
      fixation of gallbladder to the inferior margin of the liver. The clinical
      features closely mimic those of acute cholecystitis. In any case, the definitive
      diagnosis is made during surgery. We report a case of gallbladder torsion in an
      80-year-old woman. She underwent laparoscopic cholecystectomy with an uneventful
      postoperative course.

PMID- 12222925
TI  - Comparison of postoperative pulmonary function tests after cholecystectomy
      performed through Kocher's incision and mini-incision.
AB  - Comparative pulmonary function after cholecystectomy performed through Kocher's
      incision and mini-incision were evaluated. One hundred patients were included and
      systematically divided into two groups of 50 each. The first group underwent
      conventional cholecystectomy and the second group underwent mini-cholecystectomy.
      Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume at 1
      second (FEV1), and peak expiratory flow rate (PEFR) were determined on the
      preoperative day and on postoperative days 1, 2, and 3. The percentage of
      reduction of VC on postoperative day 1 (P < 0.01), 2 (P < 0.01), and 3 (P < 0.01)
      after Kocher's incision was more than the percentage of reduction after mini
      incisions on the corresponding day, respectively (P < 0.01, P < 0.01, and P <
      0.01). The percentage of reduction of FVC (P = 0.0001, 0.0001, and 0.0001) was
      lesser after mini-incision cholecystectomy than after Kocher's incision
      cholecystectomy on the three corresponding postoperative days. The percentage of
      reduction of FEV1 after mini-incision was lesser than after Kocher's incision
      cholecystectomy on the three corresponding postoperative days (P = 0.001, 0.000,
      and 0.000). There was no significant difference in PEFR between the two groups on
      the three corresponding postoperative days (P = 0.731, 0.652, and 0.393). It is
      observed that min-incision cholecystectomy is followed by superior postoperative
      pulmonary function to that seen after Kocher's incision.

PMID- 12222926
TI  - Histopathological assessment of the liver in cholelithiasis with cholecystitis.
AB  - Liver function and histology were studied in 62 patients undergoing elective
      cholecystectomy. Data from 50 of the cases was subsequently analyzed. Liver
      function was assessed by biochemical parameters and histological examination of
      intraoperatively obtained core and wedge liver biopsy. There were no
      complications associated with the procedure of liver biopsy. Seventy-eight
      percent of liver biopsies showed some form of abnormality, the commonest being
      mild portal tract infiltration. Eighteen percent of patients had severe
      histological abnormalities. Fourteen percent of bile samples were infected. No
      correlation was found among age, symptom duration, liver function tests, and
      histological appearance. Biliary infection was associated with a significant
      incidence of fatty change and inflammatory cell infiltration of parenchyma. We
      observed a high rate of abnormal liver histology of unknown clinical significance
      in patients of calculous cholecystitis. These changes are not reflected in
      commonly performed tests of liver function. Intraoperative liver biopsy is a safe
      and sensitive method to detect liver abnormalities.

PMID- 12222927
TI  - emm Typing of group A streptococcus clinical isolates: identification of dominant
      types for throat and skin isolates.
AB  - T and emm types were determined for group A streptococci isolated from patients
      with various infections during 1990-1999 in Toyama Prefecture, Japan. Out of 906
      isolates, 872 isolates were divided into 20 T serotypes, and 34 isoltes were T
      nontypeable (TNT). T12, T1, and T4 were dominant among 699 throat isolates; on
      the other hand, T11, T28, TB3264, and TNT were dominant among 80 skin isolates.
      The emm types of 190 isolates were determined following specific PCR
      amplification and sequencing of the products. Twenty T serotypes were divided
      into 34 T type/emm type combinations. Thirty-four TNT isolates were divided into
      14 emm types, in which emm58 was the most common (38%). Among 82 throat isolates
      randomly selected, predominant T types T12, T1, and T4 isolates were of the
      respective same numbers in emm type. T11/emm89, T28/emm28, TB3264/emm13w, and
      TNT/emm58 were predominant among 80 skin isolates. emm-type distribution observed
      in the present study was that usually reported in the western world. To our
      knowledge, 3 T/emm is a novel combination. These results show that emm typing
      allows the characterization of group A streptococci from various sources.

PMID- 12222928
TI  - KP-103, a novel triazole derivative, is effective in preventing relapse and
      successfully treating experimental interdigital tinea pedis and tinea corporis in
      guinea pigs.
AB  - The therapeutic efficacy of KP-103, a triazole derivative, for 10 guinea pigs
      with interdigital tinea pedis or tinea corporis was investigated. Topical KP-103
      solution (0.25 to 1%) was dose-dependently effective in treating both
      dermatophytoses. A 1% KP-103-treatment rendered all infected skins culture
      negative on day-2 posttreatment. A high negative-culture rate was obtained with
      1% solutions of butenafine and lanoconazole but not with 1% neticonazole
      solution. The follow up study performed on day-30 and day-9 posttreatment
      demonstrated that the relapse rates for 1% KP-103-treated animals with tinea
      pedis and for those with tinea corporis were 20 and 30%, respectively, and that
      these values were the same as those for 1% butenafine-treated animals, but lower
      than those for 1% lanoconazole-treated animals (55 and 80%, respectively). When a
      single dose of 1% KP-103 was applied to the back skin 48 hr before fungal
      inoculation, 9 of the 10 animals were protected from the dermatophytosis,
      suggesting that active KP-103 is retained in skin tissue for at least 48 hr after
      dosing. Moreover, it was suggested that KP-103 retains a high activity in the
      horny layer because of its lower keratin-affinity. The effectiveness of KP-103
      against dermatophytoses may be due to the favorable pharmacokinetic properties in
      the skin tissues, together with its potent antifungal activity.

PMID- 12222929
TI  - In vivo fungicidal effect of KP-103 in a guinea pig model of interdigital tinea
      pedis determined by using a new method for removing the antimycotic carryover
      effect.
AB  - We developed a new technique for culture study that successfully recovers fungi
      from drug-treated skin tissues, in which tissue specimens were homogenized,
      dialyzed against water, digested with trypsin, and then washed with PBS, to
      eliminate the drug that remaining in the skin tissue specimens. With this
      modified culture method, we reevaluated the efficacy of KP-103, neticonazole, and
      lanoconazole in a guinea pig interdigital tinea pedis model. Guinea pigs with
      tinea pedis were topically treated with a 1% solution of KP-103 or a reference
      drug once a day for 10 consecutive days. Five days after the last treatment, left
      and right feet were subjected to culture study by the conventional and modified
      recovery culture methods, respectively. One hundred percent (20/20) of
      lanoconazole-treated feet were judged as culture-negative by the conventional
      culture method, but 85% (17/20) of the feet were shown to be culture-positive
      when the modified recovery culture method was used. On the other hand, KP-103
      achieved high rates of culture-negative rates, 95% (19/20) and 85% (17/20), in
      both conventional and modified culture methods, respectively. Furthermore, on day
      30 posttreatment, KP-103 sterilized 14 of the 20 infected feet, whereas
      neticonazole and lanoconazole were not effective even in reducing fungal burden.
      KP-103 proved to be highly effective in achieving mycological cure and preventing
      relapse against tinea pedis presumably because of its good bioavailability in the
      skin based on its low keratin-affinity, along with its potent antifungal
      activity.

PMID- 12222930
TI  - Intraperitoneal immunization led to T cell hyporesponsiveness to Helicobacter
      pylori infection in mice.
AB  - During Helicobacter pylori infection, T cell response is critical in the
      development of active gastritis and in protective immunity against infection. We
      studied gastric inflammation and T cell response in H. pylori-challenged mice
      following an intraperitoneal immunization, using whole H. pylori lysate (HpAg) in
      the absence of adjuvants. H. pylori-challenged mice without immunization
      developed moderate to severe gastric inflammation, and splenocytes from these
      mice produced Th1 polarizing cytokines in response to HpAg and Con A during the
      acute infection. On the other hand, immunized-challenged mice (those inoculated
      with H. pylori following immunization) had little or no gastric inflammation
      despite persistent H. pylori colonization. Our immunization primed splenocytes to
      produce IL-2, IFN-gamma, and IL-4 in response to HpAg and Con A before infection.
      However, these cells became hyporesponsive to both stimulants immediately after
      live bacterial challenge in terms of the production of these cytokines,
      especially IL-2 and IFN-gamma. CTLA-4 has been documented to be a negative
      regulator of IL-2 production and lymphoproliferation that induces peripheral
      tolerance and functions 24-72 hr after the initiation of T cell activation.
      Compared with challenged mice, T cells from immunized-challenged mice showed
      higher levels of CTLA-4 expression at 72 hr after oral challenge. These data
      suggested that our immunization inhibited the development of H. pylori-associated
      gastritis and induced T cell hyporesponsiveness to H. pylori infection, which
      might be mediated by the early induction of CTLA-4 following challenge.

PMID- 12222931
TI  - Studies on the escape mutants of rabies virus which are resistant to
      neutralization by a highly conserved conformational epitope-specific monoclonal
      antibody #1-46-12.
AB  - We investigated a virus-neutralizing conformational epitope of the rabies virus
      glycoprotein (G) that is recognized by an anti-G monoclonal antibody (mAb; #1-46
      12) and shared by most of the laboratory strains of the virus. To investigate the
      epitope structure, we isolated escape mutants from the HEP-Flury virus (wild
      type; wt) after repeated passages in culture in the presence of the mAb.
      Immunofluorescence studies indicated that the mutants could be classified into
      two groups; the Group I lacked the epitope, while Group II preserved the epitope.
      The latter was dominant under the passage conditions, since Group I disappeared
      during the continuous passages. G proteins showed different electrophoretic
      mobilities; G protein of Group I migrated at the same rate as wt G protein, while
      that of Group II migrated at a slower rate, which was shown to be due to
      acquisition of an additional oligosaccharide side chain. Nucleotide sequencing of
      the G gene strongly suggested that amino acid substitutions at Thr-36 by Pro and
      Ser-39 by Thr of the G protein are responsible for the escape mutations of Groups
      I and II, respectively. The latter is a unique mutation of the rabies virus that
      allows the G protein to be glycosylated additionally at Asn-37, a potential
      glycosylation site that is not glycosylated in the parent virus, in preserving
      the epitope-positive conformation. These results suggest that to keep the 1-46-12
      epitope structure is of greater survival advantage for the virus to escape the
      neutralization than to destroy it, which could be achieved by acquiring an
      additional oligosaccharide chain at Asn-37.

PMID- 12222932
TI  - Studies on the rabies virus RNA polymerase: 3. Two-dimensional electrophoretic
      analysis of the multiplicity of non-catalytic subunit (P protein).
AB  - We described previously (Takamatsu et al., 1998. Microbiol. Immunol. 42: 761-771)
      the rabies virus P protein as being composed of several components of different
      sizes, among which the full-sized major components were termed as p40 and p37
      according to their electrophoretic mobilities, and radiolabeling studies with
      [32P]phosphate implied that p40 was a hyperphosphorylated form. We further
      examined here these proteins by two-dimensional (2-D) gel electrophoresis and
      immunoblotting, showing that a major component, p37, was composed of multiply
      modified subcomponents of different pIs (termed p37-1, p37-2, p37-3, etc., based
      on their acidity) in the virion and infected cells, but the unmodified precursor
      (termed p37-0) was little in amount. The viral nucleocapsid (NC)-bound P proteins
      were composed of multiple forms of p37 (the major one was p37-1) and also a minor
      component, p40-1. P proteins which were bound to newly synthesized free N
      proteins were mostly composed of p37-1, indicating that hyperphosphorylation of P
      proteins occurred after their being used for the encapsidation. Treatment of the
      infected cells with okadaic acid induced accumulation of the more acidic forms of
      P proteins, suggesting that heterogeneity in the full-sized P proteins is a
      reflection of their dynamic aspects of multiple cycles of phosphorylations and
      dephosphorylations in the cell. Two-D gel analyses demonstrated also that p40 was
      not so acidic as we expected, and implied that our previous data of apparent
      hyperphosphorylation of p40 was due to very frequently recycled utilization of
      the protein, and preformed non-labeled P proteins were also 32P-phosphorylated in
      a radiolabeling period and were converted to the p40.

PMID- 12222933
TI  - Antibacterial effect of Kampo herbal formulation Hochu-ekki-to (Bu-Zhong-Yi-Qi
      Tang) on Helicobacter pylori infection in mice.
AB  - Because Helicobacter pylori (H. pylori) infection is a major cause of
      gastroduodenal diseases in humans, the eradication of H. pylori using antibiotics
      is very effective for the treatment of gastroduodenal diseases. However, it has
      recently been reported that resistance to these antibiotics is developing. In the
      present study, the antibacterial effect of a Kampo (traditional Japanese
      medicine) herbal formulation, Hochu-ekki-to (RET; Formula repletionis animalis et
      supletionis medii), against H. pylori was examined in vitro and in vivo. HET
      inhibited the growth of antibiotic-resistant strains of H. pylori as well as
      antibiotic-sensitive strains at a dose of 2.5 mg/ml in vitro. When 1,000 mg/kg of
      HET was administered orally to C57BL/6 mice for 7 days before or after
      inoculation with H. pylori, H. pylori in the stomach was significantly reduced in
      the HET-pre-treatment group compared with the control group. Furthermore, HET in
      combination with antibiotics completely eradicated the bacteria in mice. The
      expression of interferon (IFN)-gamma was induced in the gastric mucosa of the
      mice pre-treated with HET. There were no significant differences between the
      colonization of H. pylori in the control and HET treatment groups in IFN-gamma
      gene-deficient mice. These results suggest that the antibacterial effect of HET
      may be partly due to IFN-gamma induction, and that HET may be clinically useful
      for treatment of H. pylori infection.

PMID- 12222934
TI  - Comparative profiles of intramacrophage behavior of Mycobacterium tuberculosis
      and Mycobacterium avium complex with different levels of virulence.
AB  - Mycobacterium tuberculosis (MTB) and M. avium complex (MAC) strains with
      different levels of virulence in mice were examined for profiles of interaction
      with murine peritoneal macrophages (Mphis). Their growth rates in Mphis were in
      these orders: H37Ra strain (attenuated) > H37Rv strain (virulent) for MTB, and N
      260 strain (moderate virulence) > MAC N-444 strain (low virulence) for MAC. MTB
      but not MAC caused the necrotic death of host Mphis in terms of increased release
      of lactate dehydrogenase from infected Mphis. The MTB H37Ra strain induced a
      greater production of reactive nitrogen intermediates (RNI) by Mphis than the MTB
      H37Rv strain did. However, this phenomenon was not observed with MAC, implying
      less important roles of RNI in the expression of Mphi antimicrobial activity
      against MAC organisms.

PMID- 12222935
TI  - Comparison of four microbial enzymes in Clostridia and Bacteroides isolated from
      human feces.
AB  - The activities of four microbial enzymes (azoreductase, nitroreductase, beta
      glucuronidase, and beta-glucosidase) in major anaerobic members of human fecal
      microflora were quantified and the influence of the host factors on expression of
      these microbial enzyme activities was also investigated. Clostridium
      paraputrificum and C. clostridiiforme showed much higher activities than other
      fecal anaerobes tested. Nitroreductase activity in C. paraputrificum isolated
      from fecal specimens of patients with colon cancer was significantly (P < 0.05)
      higher than that in the clostridia isolated from healthy subjects and the
      subjects given high beef diets. However, the activities of some microorganisms
      tested showed marked differences in each strain.

PMID- 12222936
TI  - Additional inhibitory effect of tea extract on the growth of influenza A and B
      viruses in MDCK cells.
AB  - It has been previously reported that green-tea extract (GTE) inhibits the growth
      of influenza virus by preventing its adsorption. In this study, we further
      investigated whether GTE exerts an additional inhibitory effect on the
      acidification of intracellular compartments such as endosomes and lysosomes
      (referred to as ELS) and thereby inhibits the growth of influenza A and B viruses
      in Madin-Darby canine kidney cells. The vital fluorescence microscopic study
      showed that GTE inhibited acidification of ELS in a concentration-dependent
      manner. Moreover, the growth of influenza A and B viruses was equally inhibited
      when the cells were treated with GTE within as early as 5 to 15 min after
      infection, depending on the virus strains. The fact that (-)epigallocatechin
      (EGC), one of major catechin molecules in GTE, exerts the inhibitory effects on
      the acidification of ELS and virus growth in a manner similar to that of GTE
      strongly suggests that EGC is one of the active components in the extract.

PMID- 12222937
TI  - An application of microplate hybridization assay for the confirmation and probe
      typing of "Norwalk-like viruses".
AB  - "Norwalk-like virus" (NLV) genomes are generally detected by using reverse
      transcription-PCR and confirmed by blot hybridization and nucleotide sequencing
      because of their fastidious nature. In the present study, the confirmation and
      typing of NLV genomes were carried out using a streptavidin-biotin binding
      technique and microplate hybridization assay with digoxigenin labeled probes.
      Eight probe typing sets (G1A, G1B, G2A, G2B, G2C, G2D, G2E, and G2F) formatted
      from 6 newly designed probes and 8 probes reported elsewhere were used for
      hybridization. The correlation between probe typing and nucleotide sequencing was
      found and our 8 probe sets were useful for the typing of NLVs.

PMID- 12222938
TI  - Expanding distribution of human serotype G6 rotaviruses in Australia.
AB  - Serotype G6 rotaviruses are common pathogens of cattle but are rarely found in
      humans. In Australia, human G6 isolates have previously been detected in two
      major southern population centres. A new isolate, ASG6.02, was detected in
      central Australia (Alice Springs) in 1997. Comparison of the deduced amino acid
      sequence of the major neutralizing antigen, VP7, indicated that ASG6.02 was
      related to human G6 viruses isolated from children in Italy and Australia.
      Phylogenetic analysis supported the close relationship between ASG6.02 and other
      Australian isolates and indicated that G6 VP7 sequences generally clustered
      according to the species of origin (human, bovine or porcine). The VP4 type of
      ASG6.02 was determined as P-type [14], in common with other isolates from
      Australia and Italy. The detection of ASG6.02 indicates that the distribution of
      this serotype is increasing in this country and may have implications for
      successful vaccine development.

PMID- 12222940
TI  - Immune responses against allogeneic and syngeneic tumors in aged C57BL/6 mice.
AB  - Aged C57BL/6 (B6) mice could reject allogeneic BALB/c RL male 1 tumor as
      efficiently as young B6 mice. However, in vitro analysis showed impaired
      generation of cytotoxic T cell response in aged B6 mice against allogeneic tumor.
      The reaction could be augmented by the addition of recombinant interleukin-2 (rIL
      2). Enzyme-linked immunospots (ELISPOT) produced by CD8+ T cells purified from
      spleen cells showed no reduction in aged mice. The findings suggested that the
      number of CD8+ T cells capable of reacting against allogeneic H-2 antigens was
      similar in young and aged B6 mice. Low cytotoxic T lymphocyte (CTL)
      responsiveness in aged B6 mice appeared to have resulted from low responsiveness
      of CD4+ T cells producing IL-2. Although CTL generation was apparently impaired,
      strong multiple antigenicity of allogeneic tumor evoked a rejection response in
      aged B6 mice. On the other hand, no rejection response was observed against
      syngeneic EL4 tumor in aged B6 mice even after depletion of CD4+ CD25+
      immunoregulatory cells. Depletion of CD4+ CD25+ cells caused rejection of EL4
      tumor in young B6 mice. The findings suggested that aged B6 mice were incapable
      of inducing effector cells against weak tumor antigens. Only marginal CTL
      response and small number of ELISPOTs were generated in young but not aged B6
      mice against EL4. Addition of rIL-2 to the culture augmented EL4 killing and
      ELISPOTs in spleen cells from young and aged B6 mice.

PMID- 12222939
TI  - Saccharomyces cerevisiae- and Candida albicans-derived mannan induced production
      of tumor necrosis factor alpha by human monocytes in a CD14- and Toll-like
      receptor 4-dependent manner.
AB  - The cytokine-inducing activities of fungal polysaccharides were examined in human
      monocytes in culture, with special reference to CD14 and Toll-like receptors
      (TLRs). Tumor necrosis factor alpha (TNF-alpha) production by monocytes was
      markedly induced in a dose-dependent manner upon stimulation with cell walls from
      Candida albicans and mannan from Saccharomyces cerevisiae and C. albicans,
      although relatively high concentrations (10 to 100 microg/ml) of stimulants were
      required for activation as compared with the reference lipopolysaccharide (LPS)
      (1 to 10 ng/ml). The yeast form C. albicans and its mannan and cell wall
      fractions exhibited higher TNF-alpha production than respective preparations from
      the hyphal form. Only slight TNF-alpha production was induced by the S.
      cerevisiae glucan. The TNF-alpha production triggered by reference LPS and
      purified fungal mannans required the presence of LPS-binding protein (LBP), and
      these responses were inhibited by anti-CD14 and anti-TLR4 antibodies, but not by
      anti-TLR2 antibody. In contrast to the activity of LPS, the activity of purified
      S. cerevisiae mannan was not inhibited by polymyxin B. These findings suggested
      that the mannan-LBP complex is recognized by CD14 on monocytes and that signaling
      through TLR4 leads to the production of proinflammatory cytokines in a manner
      similar to that induced by LPS.

PMID- 12222941
TI  - The comparative risks of bacterial contamination between a venturi atomizer and a
      positive displacement atomizer.
AB  - INTRODUCTION: This laboratory study determined the incidence of internal
      contamination of Venturi principle atomizers and positive displacement atomizers
      exposed to high external concentrations of Staphylococcal aureus (Staph).
      METHODS: Atomizer device nozzle tips were immersed into a Staph solution and I ml
      of spray was atomized via compressed wall air (Venturi) or hydraulic pump
      (positive displacement). The Venturi nozzle was then wiped with 70% isopropyl
      alcohol while the disposable positive displacement nozzle was replaced. After 30
      minutes, 1 ml of atomized fluid was collected and cultured and the process was
      repeated. After sixteen uses the fluid remaining in the bottles was cultured. The
      Venturi atomizer also was subjected to a single use trial to determine the
      location of device contamination. RESULTS: Venturi atomizers sprays grew Staph in
      every case (144/144), while positive displacement atomizer sprays never grew
      contaminants (0/144; p < 0.0001). At the end of 16 uses, 7/9 of Venturi atomizers
      had Staph within their medication reservoirs while none (0/9; p = 0.002) existed
      in the positive displacement atomizers. After a single use of the Venturi
      atomizer, the medication reservoir, the air lumen and the medication lumen of the
      nozzle were all contaminated with Staph. CONCLUSIONS: External bacterial
      contamination of the atomizer nozzle tip results in internal bacterial
      contamination of Venturi devices in as little as one use but not of positive
      displacement devices. These results warrant further investigation to determine
      whether a risk of cross-contamination exists in a clinical setting.

PMID- 12222942
TI  - Endonasal sinus surgery: extended versus limited approach.
AB  - BACKGROUND: This study was designed to investigate whether two different surgical
      approaches in endonasal sinus surgery lead to different postoperative results in
      patients with chronic rhinosinusitis. METHODS: Sixty-five patients suffering from
      chronic rhinosinusitis were operated on with either a limited approach or an
      extended approach. They were examined preoperatively and reassessed during 3
      months, 6 months, and long-term follow-up visits that included endoscopy,
      saccharin transport time, and the assessment of symptoms. RESULTS: The concept of
      this study was prospective, randomized, and multicenter (Mainz, Germany, and
      Moscow, Russia). The results of the two different surgical approaches were
      compared with each other. CONCLUSION: Surgical results and symptomatology were
      similar in both groups of patients, suggesting that a conservative approach may
      be sufficient in most patients.

PMID- 12222943
TI  - Comparison of endoscopic sinus surgery with and without image guidance.
AB  - BACKGROUND: Image guidance based on preacquired computed tomography scans of the
      patient is a technique used to assist the physician during endoscopic sinus
      surgery (ESS). This study seeks to compare ESS with and without image guidance,
      analyzing a number of parameters that can impact on efficacy. METHODS:
      Retrospective chart review took place at a tertiary care referral center. The
      study group consisted of 97 consecutive patients confirmed to have undergone ESS
      using an electromagnetic intraoperative image guidance system (IGS). The control
      group consisted of 61 consecutive patients who underwent ESS, before the IGS was
      available at the study hospital. The main outcomes measured were analysis of
      patient profile, including coexisting conditions such as asthma and polyposis,
      assessment of which specific sinuses underwent surgical treatment; major and
      minor complications; estimated blood loss (EBL); operative time; and the need for
      repeat surgery. RESULTS: The IGS group had 74% of patients with polyposis; more
      sinuses, on average, which underwent surgical revision; one major and three minor
      complications; an average EBL of 134 cc, an average procedure time of 154
      minutes; and one patient who needed repeat surgery in a 3-month follow-up period.
      The non-IGS group had 40% of patients with polyposis; seven major complications
      and one minor complication; an average EBL of 94 cc; and three patients who
      needed repeat surgery within 3 months. CONCLUSIONS: The use of an IGS for
      endoscopic sinus surgery may reduce the complications associated with the
      procedure and allow for a more thorough operation. However, operative time and
      EBL may be increased.

PMID- 12222944
TI  - A diagnostic dilemma for chronic rhinosinusitis: definition accuracy and
      validity.
AB  - BACKGROUND: The current definition of chronic rhinosinusitis is a symptom-based
      definition with minimal reliance on objective information. Based on this
      definition, patients are diagnosed and treatedl with medical therapy. A computed
      tomography (CT) scan is obtained only if the patient is not improved after
      medical therapy. No study is available evaluating in an evidence-based manner the
      accuracy of the current definition and its impact on diagnosis and treatment.
      METHODS: This study represents 78 patients evaluated in a prospective fashion who
      met the subjective criteria for the definition of chronic rhinosinusitis. All
      patients underwent a complete history with a questionnaire evaluating symptom
      severity, a physical exam including anterior rhinoscopy and endoscopy, and a CT
      scan obtained on the day of their initial visit. Objective CT scan findings were
      compared with the subjective findings and related to the ultimate diagnosis of
      chronic sinusitis. RESULTS: Only 37/78 (47%) had a positive (+) CT scan,
      indicating demonstrable sinusitis. There also was no real diffrence in symptom
      severity between patients with positive (+) and negative (-) CT scanning.
      CONCLUSION: The current symptom-based definition of chronic sinusitis poorly
      predicts whether a patient truly has chronic sinusitis and needs reevaluation.

PMID- 12222945
TI  - Correlation between rhinometric measurement methods in healthy young adults.
AB  - The most common rhinometric measurement methods used in modern rhinology are
      acoustic rhinometry, rhinomanometry, and nasal peak expiratory flow (PEF) rate.
      In this prospective study, we wanted to clarifiy whether the parameters given by
      these three methods in the same subject support each other and can be used
      simultaneously in clinical practice. We also wanted to define the dimensions of
      normal nasal geometry and function based on these three methods. The rhinometric
      measurements were done in 249 healthy white subjects consisting of 171 women and
      78 men. The geometry was analyzed with regard to body mass index (BMI) and
      smoking habits. The result could he used as some kind of reference value for the
      same kind of patient cohort as when rhinological pathology is investigated. The
      measurements obtained by acoustic rhinometry showed only statistically
      significant correlations between the measured volume and minimal cross-sectional
      area in the nasal cavities (r = 0.959). Rhinomanometry showed only a
      statistically significant correlation between the measured resistance in
      expiration and inspiration (r = 0.977). Acoustic rhinometry, rhinomanometry, and
      nasal PEF did not show any correlations and the BMI did not have any effect on
      the results. Although the smoking group was relatively small in this cohort, the
      rhinometric methods showed smaller nasal cavity volume, higher resistance, and
      lower nasal PEF values. Based on these results, we recommend the use of these
      three rhinometric methods as independent instruments in rhinological
      examinations. However, in the pathological nose, e.g., smokers, the methods show
      equal changes in measurements. It is important to measure at least acoustic
      rhinometry and rhinomanometry at the same time in clinical practice to achieve
      good quality of examinations.

PMID- 12222946
TI  - Correlation between the minimal cross-sectional area of the nasal cavity and body
      surface area: preliminary results in normal patients.
AB  - Nasal symptoms often are inconsistent with rhinoscopic findings. However, the
      proper diagnosis and treatment of nasal pathology requires an objective
      evaluation of the narrow segments of the anterior part of the nasal cavities
      (minimal cross-sectional area [MCSA]). The problem is that the value of MCSA is
      not a unique parameterfor the entire population, but rather it is a distinctive
      valuefor particular subject (or smaller groups of subjects). Consequently, there
      is a need for MCSA values to be standardized in a simple way that facilitates the
      comparison of results and the selection of our treatment regimens. We examined a
      group of 157 healthy subjects with normal nasal function. A statistically
      significant correlation was found between the body surface area and MCSA at the
      level of the nasal isthmus and the head of the inferior turbinate. The age of
      subjects was not found a statistically significant predictor for the value of
      MCSA. The results show that the expected value of MCSA can be calculated for
      every subject based on anthropometric data of height and weight.

PMID- 12222947
TI  - Mucociliary transport function and damage of ciliated epithelium.
AB  - The influence of epithelial damage on mucociliary transport was studied in
      relation to the amount of mucus. The mucosal epithelium of mucus-depleted frog
      palate was dissected and mounted on a plastic plate. Mechanical damages were
      created on the frog mucosa by pressing a different thickness of boards (2, 3, 5,
      and 8 mm). Two different amounts of frog mucus (7.9 microL [small amount of mucus
      (S-mucus]]) and 51.0 microL [large amount of mucus [L-mucus]]) were acpplied on
      the frog mucosa witih and without mucosal damage. There was no difference in
      mucociliary transport rate (MTR) on undamaged frog mucosa between S-mucus and L
      mucus. However, on the damaged mucosa, MTR of S-miucus was significantly
      decreased compared with that of L-mucus. Moreover, capability of mucus
      transportation across the mucosal damage was significantly lower in S-mucus than
      in L-mnucus. Results indicate that the larger the mucus amount becomes, the more
      the mucus travels the damaged epithelium. Moreover, MTR of L-mucus was decreased
      with increasing the degree of epithelial damage. This study indicates that the
      degree of loss of cilia is an important factor of mucociliarn deceleration.

PMID- 12222948
TI  - Endoscopic management of benign sinonasal tumors: a decade of experience.
AB  - BACKGROUND: A variety of benign tumors present in the nasal and paranasal
      sinuses. METHODS: We review our experience over the last 10 years with endoscopic
      management of these tumors and discuss (presentation, diagnostic considerations,
      and therapeutic options. RESULTS: Eighteen patients with benign sinonasal tumors
      were managed with endoscopic techniques. Representative cases are presented,
      including pleomorphic adenoma, ameloblastoma, meningioma, cholersterol granuloma,
      ossifying fibroma, fibrous dysplasia, and osteomas. Three patients (16.7%)
      required one revision endoscopic sinus procedure. Average follow-up was 4 years.
      CONCLUSIONS: With the treatment of more complex cases being undertaken
      endoscopically, the need for individual therapeutic consideration and close
      follow-up is stressed. The combination of removal of benign tumors endoscopically
      and endoscopic surveillance in the outpatient setting has allowed a less radical
      surgical approach while resulting in decreased morbidity and better tumor
      control.

PMID- 12222949
TI  - The effect of topical xylometazoline on the mucosal temperature of the nasal
      septum.
AB  - BACKGROUND: The purpose of this study was to determine the short-term influence
      of the alpha2-adrenoreceptor agonist xylometazoline on the nasal mucosal
      temperature. METHODS: Thirty healthy subjects were enrolled into the study.
      Fifteen of these subjects got xylometazoline and 15 subjects, matched to age, got
      saline solution as control. A miniaturized thermocouple was used for continuous
      detection of the septal mucosal temperature without interruption of nasal
      breathing before and after application of nose spray. RESULTS: In the anterior
      nasal segment, the mucosal temperatures before decongestion were significantly
      higher than after decongestion (p < 0.05). These changes could not be found in
      the control group after saline solution. The mean end-expiratory mucosal
      temperatures were significantly higher than the end-inspiratory ones in both
      study groups (p < 0.005). CONCLUSIONS: The reduction of the nasal mucosal
      bloodflow because of vasoconstriction and the increase of the nasal cavity volume
      after decongestion with xylometazoline seem to cause a significant decrease of
      the septal mucosal temperature in the anterior nasal segment. This might be one
      possible causative factor of the common symptom of the "dry nose" in patients
      with nasal decongestant abuse.

PMID- 12222950
TI  - Microbial aspects of atrazine degradation in natural environments.
AB  - The potential toxicity of the s-triazine herbicide atrazine motivates continuous
      bioremediation-directed research. Several indigenous soil atrazine-catabolizing
      microbial associations and monocultures have been enriched/isolated from
      compromised sites. Of these, Pseudomonas sp. strain ADP has become a reference
      strain and has been used to elucidate sequences of the catabolic enzymes atzA,
      atzB, atzC and atzD involved in one aerobic degradation pathway and develop
      probes for the genes which encode these enzymes. Despite this, hitherto unknown
      or novel microorganisms, with unique sequences and different enzyme-mediated
      operative pathways, warrant continued investigations for effective site
      bioremediation. Also, the sustained effectiveness of natural attenuation must be
      demonstrated continually so regular site evaluations and results analyses,
      despite the limitations of chemical extraction methodologies, are crucial
      practices. For both directed and intrinsic bioremediation monitoring, traditional
      microbial association studies must be complemented by more advanced physiological
      and molecular approaches. The occurrence of catabolic plasmids, in particular,
      should be probed with DNA hybridization techniques. Also, PCR-DGGE and subsequent
      new sequence elucidation should be used prior to developing new primers for DNA
      sequences encoding novel catabolic enzymes, and for hybridization probe
      development, to establish the degradative potential of a compromised site, or
      adoption of FISH to, for example, monitor bioaugmented remediation.

PMID- 12222951
TI  - Resilience of the rhizosphere to anthropogenic disturbance.
AB  - The rhizosphere is a dominant site of microbial metabolism in soil and whereas it
      can be shown that anthropogenic disturbances can influence this metabolism, the
      impact of these disturbances on biodiversity is rather difficult to determine at
      the species level. This is in part because no more than 10% of the microbial
      species are culturable, and in part because there is very poor precision in plate
      counting, usually requiring a change of 300-500% to be significant. We have
      therefore used a functional approach. The 'ecophysiological index' is based on r
      or K strategy of the organisms being counted. Also, enzyme families, microbial
      biomass, microbe/microbe and microbe/fauna interactions have been determined,
      along with nutrient uptake measurements. The techniques have been applied to
      determine the effects of disturbances created by the introduction of GM plants
      and microorganisms to soil, these effects being small compared with those caused
      by time-honoured practices such as crop rotation and ploughing. Toxicity from
      industrial influences (e.g. cyanide) can be remediated by rhizosphere
      microorganisms.

PMID- 12222952
TI  - Effects of agronomical measures on the microbial diversity of soils as related to
      the suppression of soil-borne plant pathogens.
AB  - The diversity of soil microbial communities can be key to the capacity of soils
      to suppress soil-borne plant diseases. As agricultural practice, as well as
      directed agronomical measures, are known to be able to affect soil microbial
      diversity, it is plausible that the soil microflora can be geared towards a
      greater suppressivity of soil-borne diseases as a result of the selection of
      suitable soil management regimes. In the context of a programme aimed at
      investigating the microbial diversity of soils under different agricultural
      regimes, including permanent grassland versus arable land under agricultural
      rotation, we assessed how soil microbial diversity is affected in relation to the
      suppression of the soil-borne potato pathogen Rhizoctonia solani AG3. The
      diversity in the microbial communities over about a growing season was described
      by using cultivation-based--plating on different media--and cultivation
      independent--soil DNA-based PCR followed by denaturing gradient gel
      electrophoresis (DGGE) community fingerprinting--methods. The results showed
      great diversity in the soil microbiota at both the culturable and cultivation
      independent detection levels. Using cultivation methods, various differences
      between treatments with respect to sizes of bacterial and fungal populations were
      detected, with highest population sizes generally found in rhizospheres. In
      addition, the evenness of eco-physiologically differing bacterial types was
      higher in grassland than in arable land under rotation. At the cultivation
      independent level, clear differences in the diversities of several microbial
      groups between permanent grassland and arable land under rotation were apparent.
      Bio-assays that assessed the growth of R. solani AG3 hyphae through soil
      indicated a greater growth suppression in grassland than in arable land soils.
      Similarly, an experiment performed in the glasshouse showed clear differences in
      both microbial diversities and suppressiveness of R. solani growth in soil,
      depending on the presence of either maize or oats as the crop. The significance
      of these findings for designing soil management strategies is discussed.

PMID- 12222953
TI  - Diffuse atrazine pollution in German aquifers.
AB  - Until its prohibition in Germany in 1991, atrazine was the most frequently
      applied herbicide in maize cultivation. Moreover, it was used in orchards and
      vineyards and as a total herbicide on non-cultivated grounds (railways, factory
      grounds). Later on, atrazine was substituted mainly by terbutylazine.
      Terbutylazine and terbutryn are the only s-triazines presently permitted in
      Germany. Nevertheless, atrazine and its metabolite desethylatrazine are by far
      the most abundant herbicides detected in near surface groundwater. This might be
      due to wash-outs from the pools of atrazine and its metabolites from the soil
      into the groundwater or continuing illegal applications. Samples taken from maize
      fields in 1994 showed that 6.2% of 471 fields tested were treated with atrazine
      despite the prohibition of its use. Nevertheless, the overall trend is in fact a
      slow decrease in atrazine concentrations where it is detected in groundwater and,
      simultaneously often a slight increase in desethylatrazine concentrations. But
      this is not the case for all sampling points, and increasing concentrations in
      several aquifers are observed as well. Factors governing the adsorption,
      degradation, persistence and the possible transfer into the aquifer and the
      current situation concerning atrazine occurrence in German aquifers will be
      discussed.

PMID- 12222954
TI  - Assessment of soil contamination--a functional perspective.
AB  - In many industrialized countries the use of land is impeded by soil pollution
      from a variety of sources. Decisions on clean-up, management or set-aside of
      contaminated land are based on various considerations, including human health
      risks, but ecological arguments do not have a strong position in such
      assessments. This paper analyses why this should be so, and what ecotoxicology
      and theoretical ecology can improve on the situation. It seems that soil
      assessment suffers from a fundamental weakness, which relates to the absence of a
      commonly accepted framework that may act as a reference. Soil contamination can
      be assessed both from a functional perspective and a structural perspective. The
      relationship between structure and function in ecosystems is a fundamental
      question of ecology which receives a lot of attention in recent literature,
      however, a general concept that may guide ecotoxicological assessments has not
      yet arisen. On the experimental side, a good deal of progress has been made in
      the development and standardized use of terrestrial model ecosystems (TME). In
      such systems, usually consisting of intact soil columns incubated in the
      laboratory under conditions allowing plant growth and drainage of water, a
      compromise is sought between field relevance and experimental manageability. A
      great variety of measurements can be made on such systems, including
      microbiological processes and activities, but also activities of the decomposer
      soil fauna. I propose that these TMEs can be useful instruments in ecological
      soil quality assessments. In addition a "bioinformatics approach" to the analysis
      of data obtained in TME experiments is proposed. Soil function should be
      considered as a multidimensional concept and the various measurements can be
      considered as indicators, whose combined values define the "normal operating
      range" of the system. Deviations from the normal operating range indicate that
      the system is in a condition of stress. It is hoped that more work along this
      line will improve the prospects for ecological arguments in soil quality
      assessment.

PMID- 12222955
TI  - Natural attenuation: what does the subsurface have in store?
AB  - Throughout the world, organic and inorganic substances leach into the subsurface
      as a result of human activities and accidents. There, the chemicals pose direct
      or indirect threats to the environment and to increasingly scarce drinking water
      resources. At many contaminated sites the subsurface is able to attenuate
      pollutants which, potentially, lowers the costs of remediation. Natural
      attenuation comprises a wide range of processes of which the microbiological
      component, which is responsible for intrinsic bioremediation, can decrease the
      mass and toxicity of the contaminants and is, therefore, the most important.
      Reliance on intrinsic bioremediation requires methods to monitor the process. The
      subject of this review is how knowledge of subsurface geology and hydrology,
      microbial ecology and degradation processes is used and can be used to monitor
      the potential and capacity for intrinsic bioremediation in the subsurface and to
      verify degradation in situ. As research on natural attenuation in the subsurface
      has been rather fragmented and limited and often allows only conclusions to be
      drawn of the site under investigation, we provide a concept based on
      Environmental Specimen Banking which will contribute to further understanding
      subsurface natural attenuation processes and will help to develop and implement
      new monitoring techniques.

PMID- 12222956
TI  - The role of microbial populations in the containment of aromatic hydrocarbons in
      the subsurface.
AB  - A survey of soil gases associated with gasoline stations on the Swan Coastal
      Plain of Western Australia has shown that 20% leak detectable amounts of
      petroleum. The fates of volatile hydrocarbons in the vadose zone at one
      contaminated site, and dissolved hydrocarbons in groundwater at another site were
      followed in a number of studies which are herein reviewed. Geochemical evidence
      from a plume of hydrocarbon-contaminated groundwater has shown that sulfate
      reduction rapidly developed as the terminal electron accepting process. Toluene
      degradation but not benzene degradation was linked to sulfate reduction. The
      sulfate-reducing bacteria isolated from the plume represented a new species,
      Desulfosporosinus meridiei. Strains of the species do not mineralise 14C-toluene
      in pure culture. The addition of large numbers of cells and sulfate to microcosms
      did stimulate toluene mineralisation but not benzene mineralisation. Attempts to
      follow populations of sulfate-reducing bacteria by phospholipid signatures, or
      Desulfosporosinus meridiei by FISH in the plume were unsuccessful, but
      fluorescently-labeled polyclonal antibodies were successfully used. In the vadose
      zone at a different site, volatile hydrocarbons were consumed in the top 0.5 m of
      the soil profile. The fastest measured rate of mineralisation of 14C-benzene in
      soils collected from the most active zone (6.5 mg kg(-1) day(-1)) could account
      for the majority of the flux of hydrocarbon vapourtowards the surface. The
      studies concluded that intrinsic remediation by subsurface microbial populations
      in groundwater on the Swan Coastal Plain can control transport of aromatic
      hydrocarbon contamination, except for the transport of benzene in groundwater. In
      the vadose zone, intrinsic remediation by the microbial populations in the soil
      profile can contain the transport of aromatic hydrocarbons, provided the physical
      transport of gases, in particular oxygen from the atmosphere, is not impeded by
      structures.

PMID- 12222957
TI  - The galactosyltransferase family.
AB  - Galactose is transferred via several linkages to acceptor structures by
      galactosyltransferase enzymes. In prokaryotes, galactose is mainly found on
      lipopolysaccharides and capsular polysaccharides. In eukaryotes,
      galactosyltransferases, which are localized in the Golgi apparatus, are involved
      in the formation of several classes of glycoconjugates and in lactose
      biosynthesis. Although they sometimes catalyze identical reactions, prokaryotic
      and eukaryotic galactosyltransferases share only little structural similarities.
      In mammals, 19 distinct galactosyltransferase enzymes have been characterized to
      date. These enzymes catalyze the transfer of galactose via beta1-4, beta1-3,
      alpha1-3 and alpha1-4 linkages. The present review focuses on the description of
      these mammalian galactosyltransferases.

PMID- 12222958
TI  - New insights into the structure and function of fatty acid-binding proteins.
AB  - Fatty acid-binding proteins (FABPs) are members of a superfamily of lipid-binding
      proteins, and occur intracellularly in vertebrates and invertebrates. This review
      presents recent findings on the diversity of these FABPs and their proposed roles
      in fatty acid (FA) metabolism and other cellular processes. Special attention is
      paid to the structural features of the different mammalian FABP types and the
      physiological role of these proteins in FA transport, cell growth and
      differentiation, cellular signalling, gene transcription and cytoprotection.
      Additionally, data on FABP knockout mice and the implication of FABP in medicine
      are discussed.

PMID- 12222959
TI  - RAGE is a multiligand receptor of the immunoglobulin superfamily: implications
      for homeostasis and chronic disease.
AB  - Receptor for AGE (RAGE) is a member of the immunoglobulin superfamily that
      engages distinct classes of ligands. The biology of RAGE is driven by the
      settings in which these ligands accumulate, such as diabetes, inflammation,
      neurodegenerative disorders and tumors. In this review, we discuss the context of
      each of these classes of ligands, including advance glycation end-products,
      amyloid beta peptide and the family of beta sheet fibrils, S100/calgranulins and
      amphoterin. Implications for the role of these ligands interacting with RAGE in
      homeostasis and disease will be considered.

PMID- 12222960
TI  - Diacylglycerol kinases in nuclear lipid-dependent signal transduction pathways.
AB  - Several independent groups have shown that lipid-dependent signal transduction
      systems operate in the nucleus and that they are regulated independently from
      their membrane and cytosolic counterparts. A sizable body of evidence suggests
      that nuclear lipid signaling controls critical biological functions such as cell
      proliferation and differentiation. Diacylglycerol is a fundamental lipid second
      messenger which is produced in the nucleus. The levels of nuclear diacylglycerol
      fluctuate during the cell cycle progression, suggesting that such a molecule has
      important regulatory roles. Most likely, nuclear diacylglycerol serves as a
      chemoattractant for some isoforms of protein kinase C that migrate to the nucleus
      in response to a variety of agonists. The nucleus also contains diacylglycerol
      kinases, i.e. the enzymes that, by converting diacylglycerol into phosphatidic
      acid, terminate diacylglycerol-dependent events. A number of diacylglycerol
      kinases encoded by separate genes are present in the mammalian genome. This
      review aims at highlighting the different isotypes of diacylglycerol kinases
      identified at the nuclear level as well as at discussing their potential function
      and regulation.

PMID- 12222961
TI  - The short proline-rich antibacterial peptide family.
AB  - From the many peptide families that are induced upon bacterial infection and can
      be isolated from all classes of animals, the short, proline-rich antibacterial
      peptides enjoy particular interest. These molecules were shown to inactivate an
      intracellular biopolymer in bacteria without destroying or remaining attached to
      the bacterial cell membrane, and as such emerged as viable candidates for the
      treatment of mammalian infections. These peptides were originally isolated from
      insects, they kill mostly gram-negative bacteria with high efficiency and they
      show structural similarities with longer insect- and mammal-derived antimicrobial
      peptides. However, while the distant relatives appear to carry multiple
      functional domains, apidaecin, drosocin, formaecin and pyrrhocoricin consist of
      only minimal determinants needed to penetrate across the cell membrane and bind
      to the target biopolymer. These peptides appear to inhibit metabolic processes,
      such as protein synthesis or chaperone-assisted protein folding. Pyrrhocoricin
      derivatives protect mice from experimental infections in vivo, suggesting the
      utility of modified analogs in the clinical setting. Sequence variations of the
      target protein at the peptide-binding site may allow the development of new
      peptide variants that kill currently unresponsive strains or species.

PMID- 12222962
TI  - Probiotic microorganisms: how they affect intestinal pathophysiology.

PMID- 12222963
TI  - Assembling the human immunodeficiency virus type 1.
AB  - Retroviral assembly proceeds through a series of concerted events that lead to
      the formation and release of infectious virion particles from the infected cell.
      Upon translation, structural proteins are targeted to the plasma membrane where
      they accumulate. There, the nascent particle forces the plasma membrane to form a
      bud, which pinches off releasing the virion particle from the cell. In this
      review we describe the molecular mechanisms now known to be behind the process of
      virion assembly. In particular, we focus on the human immunodeficiency virus type
      1, the prototype member of the lentivirus subfamily of the Retroviridae.

PMID- 12222964
TI  - Proinsulin C-peptide and its analogues induce intracellular Ca2+ increases in
      human renal tubular cells.
AB  - Based on the findings that proinsulin C-peptide binds specifically to cell
      membranes, we investigated the effects of C-peptide and related molecules on the
      intracellular Ca2+ concentration ([Ca2+]i) in human renal tubular cells using the
      indicator fura-2/AM. The results show that human C-peptide and its C-terminal
      pentapeptide (positions 27-31, EGSLQ), but not the des (27-31) C-peptide or
      randomly scrambled C-peptide, elicit a transient increase in [Ca2+]i. Rat C
      peptide and rat C-terminal pentapeptide also induce a [Ca2+]i response in human
      tubular cells, while a human pentapeptide analogue with Ala at position 1 gives
      no [Ca2+]i response, and those with Ala at positions 2-5 induce responses with
      different amplitudes. These results define a species cross-reactivity for C
      peptide and demonstrate the importance of Glu at position 1 of the pentapeptide.
      Preincubation of cells with pertussis toxin abolishes the effect on [Ca2+]i by
      both C-peptide and the pentapeptide. These results are compatible with previous
      data on C-peptide binding to cells and activation of Na-,K+ATPase. Combined, all
      data show that C-peptide is a bioactive peptide and suggest that it elicits
      changes in [Ca2+]i via G-protein-coupled pathways, giving downstream enzyme
      effects.

PMID- 12222965
TI  - Peroxovanadate inhibits Ca2+ release from mitochondria.
AB  - Mitochondria contain a specific Ca2+ release pathway which operates when oxidized
      mitochondrial pyridine nucleotides are hydrolyzed. NAD+ hydrolysis and therefore
      Ca2+ release is possible when some vicinal thiols are cross-linked. Here we
      report that the thiol oxidant peroxovanadate inhibits the specific Ca2+ release
      pathway. In mitochondria, peroxovanadate causes a complete loss of reduced
      glutathione, which is not accompanied by formation of glutathione disulfide, and
      a partial loss of protein thiols. In model reactions, peroxovanadate oxidizes
      reduced glutathione predominantly to the sulfonate derivative, but does not react
      with glutathione disulfide. When the vicinal thiols relevant for Ca2+ release are
      cross-linked, Ca2+ release is no longer inhibited by peroxovanadate. Conversely,
      pretreatment of mitochondria with peroxovanadate makes them insensitive to
      compounds promoting the disulfide state. These results suggest that
      peroxovanadate inhibits the prooxidant-induced Ca2+ release from mitochondria by
      (i) depleting mitochondria of reduced glutathione and (ii) oxidizing the vicinal
      thiols relevant for Ca2+ release to a state higher than disulfide, presumably the
      sulfonate state. The findings provide further insight into the regulation of Ca2+
      release from intact mitochondria, and may be relevant for a better understanding
      of the action of peroxovanadate in cells, where the compound can be insulin
      mimetic.

PMID- 12222966
TI  - Survival of docetaxel-resistant prostate cancer cells in vitro depends on
      phenotype alterations and continuity of drug exposure.
AB  - We evaluated in vitro the effect of paclitaxel and docetaxel on PC-3 and DU-145
      prostate cancer cell lines to understand better the downstream events in drug
      induced tumor cell death. Taxane treatments of DU-145 cells induced rapid cell
      death by apoptosis, but in PC-3 cells, treatments achieved growth arrest,
      followed by extensive karyokinesis resulting in multinucleation, giant-cell
      formation and delayed cell death. To determine if the giant multinucleated cells
      were able to produce proliferating and drug-resistant survivors, we first
      delineated the kinetics of drug activity and cytotoxic dose range. Analysis of
      both lines by colorimetric and cell viability assays demonstrated improved
      cytotoxicity of taxanes applied continuously. Selected doses and schedules of
      docetaxel were used to induce giant multinucleated cells that gave rise to
      docetaxel-resistant survivors, which remained sensitive to paclitaxel and other
      chemotherapeutics. Growth and morphology of the recovered clones was similar to
      parental cells. The resistant phenotype of these clones determined by
      immunofluorescence and immunoblot was associated with transient expression of the
      beta-tubulin i.v. isoform and was independent of P-glycoprotein, bcl-2 and bcl
      xL. Resistant clones will be useful to model progression of resistance to taxanes
      and to identify unknown and clinically important molecular mechanisms of cell
      death and resistance.

PMID- 12222967
TI  - Gene structure of the murine 2'-5'-oligoadenylate synthetase family.
AB  - The 2'-5'-oligoadenylate synthetases (OASs) are members of a family of interferon
      induced proteins playing an important role in the antiviral effect of interferons
      as well as being involved in apoptosis and control of cellular growth. Based on
      sequence data from the murine BAC clone (RP23-39M18), and a number of EST and
      IMAGE clones and the Celera Mouse database, we identified twelve Oas genes in the
      mouse genome, all localized to the chromosome 5F region. In contrast to the
      single OAS1 gene found in humans, we identified eight closely linked Oas1 genes
      in the murine genome, together with the genes of Oas2 and Oas3. Compared to the
      single OASL gene found in humans, two genes of OAS-like proteins, Oasl1 and
      Oasl2, were identified. All the putative genes seem to be transcribed. The
      exon/intron structures of the murine Oas genes were found to be identical to
      those of the human genes.

PMID- 12222968
TI  - The 2.4-A crystal structure of the penicillin-resistant penicillin-binding
      protein PBP5fm from Enterococcus faecium in complex with benzylpenicillin.
AB  - Penicillin-binding proteins (PBPs) are membrane proteins involved in the final
      stages of peptidoglycan synthesis and represent the targets of beta-lactam
      antibiotics. Enterococci are naturally resistant to these antibiotics because
      they produce a PBP, named PBP5fm in Enterococcus faecium, with low-level affinity
      for beta-lactams. We report here the crystal structure of the acyl-enzyme complex
      of PBP5fm with benzylpenicillin at a resolution of 2.4 A. A characteristic of the
      active site, which distinguishes PBP5fm from other PBPs of known structure, is
      the topology of the loop 451-465 defining the left edge of the cavity. The
      residue Arg464, involved in a salt bridge with the residue Asp481, confers a
      greater rigidity to the PBP5fm active site. In addition, the presence of the
      Val465 residue, which points into the active site, reducing its accessibility,
      could account for the low affinity of PBP5fm for beta-lactam. This loop is common
      to PBPs of low affinity, such as PBP2a from Staphylococcus aureus and PBP3 from
      Bacillus subtilis. Moreover, the insertion of a serine after residue 466 in the
      most resistant strains underlines even more the determining role of this loop in
      the recognition of the substrates.

PMID- 12222969
TI  - Is there a relationship between hypertension and cognitive function in older
      adults?

PMID- 12222970
TI  - The case for hormone replacement: new studies that should inform the debate.
AB  - The Women's Health Initiative found that the risks of hormone replacement therapy
      (HRT) exceeded its benefits in a large group of older postmenopausal women, but
      did not consider the efficacy of HRT in relieving vasomotor symptoms. Another
      recent study found that low-dose HRT was as effective as standard-dose HRT while
      causing fewer side effects. Smaller studies suggest that HRT may improve
      depression. HRT is not to be used for cardiovascular risk reduction. Genetic
      testing may point the way to more rational use of HRT.

PMID- 12222971
TI  - Patient information. Hormone replacement therapy: frequently asked questions.

PMID- 12222972
TI  - Hormone replacement therapy: applying the results of the Women's Health
      Initiative.

PMID- 12222973
TI  - Choosing the most appropriate valve operation and prosthesis.
AB  - Repairing a diseased heart valve is usually better than replacing it. However,
      repair is not always feasible. No valve is ideal, and patients should be informed
      of the risks associated with each. The decision requires close discussion among
      the patient, the physician, and the surgeon.

PMID- 12222974
TI  - What internists need to know about postpolio syndrome.
AB  - Decades after recovery from polio, many patients develop new muscle weakness and
      other symptoms that can lead to increased debility. Treatment is aimed at the
      most prominent symptoms. Medications may help, as well as physical therapy and a
      carefully paced exercise program. Screening for osteopenia and osteoporosis is
      recommended.

PMID- 12222975
TI  - The ACUTE trial. Transesophageal echocardiography to guide electrical
      cardioversion in atrial fibrillation. Assessment of Cardioversion Using
      Transesophageal Echocardiography.
AB  - The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE)
      trial compared cardioversion following transesophageal echocardiography (TEE)
      against conventional management of atrial fibrillation (ie, cardioversion
      following 3 weeks of anticoagulation) in patients scheduled to undergo electrical
      cardioversion.

PMID- 12222976
TI  - The crystal, the gout, and the paradox.

PMID- 12222977
TI  - Advances in diagnosing and excluding pulmonary embolism: spiral CT and D-dimer
      measurement.
AB  - No single imaging study or blood test is 100% sensitive and specific for
      pulmonary embolism. A combination of pretest clinical probability assessment,
      noninvasive pulmonary imaging (V/Q scanning or spiral CT), and D-dimer testing
      seems prudent before pursuing pulmonary angiography.

PMID- 12222978
TI  - Acute stroke therapy: beyond i.v. tPA.
AB  - Although intravenous tissue plasminogen activator (i.v. tPA) has been approved
      for treating acute ischemic stroke, it must be given within 3 hours of stroke
      onset and only after ruling out hemorrhagic stroke by computed tomography.
      Several medical centers are turning to angiography to guide intra-arterial
      infusion of thrombolytic agents and mechanical endovascular interventions.

PMID- 12222979
TI  - Mass spectrometry of free radicals.

PMID- 12222980
TI  - Novel multifunctional polymers from aromatic diamines by oxidative
      polymerizations.

PMID- 12222981
TI  - The chemistry of beta-diketiminatometal complexes.

PMID- 12222982
TI  - Some aspects of the properties and degradation of polyacrylamides.

PMID- 12222983
TI  - Chemical vapor deposition methods for the controlled preparation of supported
      catalytic materials.

PMID- 12222984
TI  - Chiral 2,2'-bipyridines, 1,10-phenanthrolines, and 2,2':6',2' '-terpyridines:
      syntheses and applications in asymmetric homogeneous catalysis.

PMID- 12222985
TI  - Density matrix analysis and simulation of electronic excitations in conjugated
      and aggregated molecules.

PMID- 12222987
TI  - Myocardial infarction in the elderly: benefits and risks of thrombolytics.
AB  - Patients aged 75 years and older comprise 36% of all patients with myocardial
      infarction and 60% of all deaths from myocardial infarction in the US. Data from
      randomised, placebo-controlled clinical trials and observational data
      demonstrated a beneficial effect of thrombolytic therapy in eligible patients
      with acute myocardial infarction younger than 75 years of age. The overall data
      support the use of thrombolytic therapy in eligible patients with acute
      myocardial infarction aged 75 years and older. There is an urgent need to conduct
      a large-scale, prospective, double-blind, randomised, placebo-controlled trial
      investigating the effect of thrombolytic therapy on the combined endpoint of all
      cause mortality plus cerebral bleeding at hospital discharge and at long-term
      follow-up in eligible patients aged 75 years and older with acute myocardial
      infarction. Current guidelines for the care of patients with acute myocardial
      infarction from the American College of Cardiology/American Heart Association
      support the use of thrombolytic therapy in eligible patients aged 75 years and
      older who present within 12 hours of symptom onset of acute myocardial infarction
      as a Class IIa indication, that is, one for which the weight of evidence/opinion
      is in favour of usefulness/ efficacy. Absolute contraindications to thrombolytic
      therapy include prior haemorrhagic stroke, other cerebrovascular events within 1
      year, active internal bleeding, known intracranial neoplasm, suspected aortic
      dissection, and acute pericarditis. Stroke is a potential risk of the use of
      thrombolytics.

PMID- 12222988
TI  - A benefit-risk assessment of medical treatment for uterine leiomyomas.
AB  - The growth of a uterine leiomyoma growth stops and regresses after the menopause
      suggesting that leiomyoma growth is dependent on ovarian steroids. Therefore,
      estrogen has received much attention as the major factor responsible for the
      development of uterine leiomyomas, but progesterone also plays an important role
      in development of this disease. Cytogenetic analyses of resected samples has
      revealed that about 40 to 50% of leiomyomas show karyotypically detectable
      chromosomal abnormalities. Gonadotrophin releasing hormone (GnRH) agonists exert
      their action through the suppression of endogenous gonadotrophins and gonadal
      steroid secretion. Significant reductions of uterine/leiomyoma volume under GnRH
      agonist therapy has been reported in several studies. However, the leiomyoma
      generally returns to its pretreatment volume within a few months after
      discontinuation of the GnRH agonist. To minimise the adverse effects of
      hypoestrogenism during GnRH agonist treatment, add back therapy can be used
      (estrogen-progestin, progestin alone and recently tibolone). Antiprogestins have
      a potential clinical utility in uterine leiomyomas. Mifepristone is a synthetic
      steroid with both antiprogesterone and antiglucocorticoid activities, that may
      have an inhibitory effect on growth of leiomyoma. Danazol is an isoxazole of
      17beta-ethinyl testosterone, a synthetic steroid, which has a suppressive effect
      on sex hormone binding globulin concentrations, resulting in efficacy in the
      short-term treatment of uterine leiomyomas. Gestrinone is a tri-enic steroid with
      antiestrogen and antiprogesterone properties and has been shown to reduce uterine
      volume and stop bleeding. Growth factors play a relevant role on the
      pathophysiology of uterine leiomyoma and probably the inhibition of the action of
      growth factors on the myometrium will be the basis for future therapy. A number
      of agents are under investigation for treating uterine leiomyoma. Agents
      developed from increasing genetic knowledge of this condition could represent, in
      the next few years, new trends in the medical treatment of uterine leiomyomas.

PMID- 12222989
TI  - Long-term tolerability of the bisphosphonates in postmenopausal osteoporosis: a
      comparative review.
AB  - Osteoporosis in postmenopausal women is a growing health concern for society.
      Bisphosphonates have become the mainstay of prevention and treatment with the
      mounting evidence of their efficacy over the past two decades. This review
      article examines the use of the etidronate, alendronate and risedronate. The
      pivotal trials are reviewed for long-term tolerability, evidence regarding
      histological safety and gastrointestinal tolerance. Etidronate, alendronate and
      risedronate have also been examined in meta-analyses, which reviewed
      methodologically sound trials. Length of treatment, adverse events and medication
      discontinuation and patients lost to follow-up were evaluated. Etidronate trials
      and the recent meta-analysis support the safe clinical use of cyclical etidronate
      with no signs of osteomalacia or other skeletal pathology over 2 to 3 years. In
      addition to increased bone mineral density (BMD) and vertebral fracture risk
      reduction, patients tolerated cyclical etidronate well up to 4 years in
      randomised studies. Non-randomised data has shown safety up to 7 years with
      clinical and bone biopsy data. Alendronate studies demonstrated similar overall
      adverse event rates, study discontinuation rates and loss to follow-up rates
      between placebo and treatment arms, in addition to consistent improvements in
      BMD, vertebral and non-vertebral fracture risk reductions over 3 to 4 years.
      Histological safety has been demonstrated up to 3 years. Longer-term therapy in
      non-randomised trials up to 7 years showed similar clinical safety between
      alendronate and placebo. Risedronate trials and the meta-analysis also showed
      similar adverse event profiles between placebo and treatment arms, as well as
      improvements in BMD, vertebral and non-vertebral fracture risk reductions up to 3
      years. Rates of discontinuation due to gastrointestinal events were similar
      between groups. Histological safety has also been demonstrated for risedronate up
      to 3 years. Each of these bisphosphonates have been shown to have comparable
      safety with placebo up to 3 to 4 years, with the most rigourous trials carried
      out for alendronate and risedronate. Long-term comparative studies are awaited.

PMID- 12222990
TI  - Benefits and risks of pharmacotherapy for narcolepsy.
AB  - Narcolepsy is a life-long central nervous system (CNS) syndrome characterised by
      excessive sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and
      disturbed night-time sleep. Unsuccessfully treated narcolepsy confers increased
      risks on patients and on society due to the patient's increased chance of
      becoming involved in vehicle crashes and workplace mishaps. The syndrome may be
      diagnosed by a clinical history positive for cataplexy and excessive daytime
      sleepiness and negative for other more common sleep disorders such as sleep
      apnoea and sleep deprivation. Night-time polysomnography and multiple sleep
      latency testing are helpful in differentiating narcolepsy from other sleep
      problems. Recent data from canine, murine, and human forms of narcolepsy indicate
      that genetically or developmentally mediated deficits in the hypocretin
      neurotransmitter system may cause some, but not all, forms of narcolepsy.
      Pharmacotherapy for narcolepsy is required to control symptoms and involves the
      use of CNS stimulants or modafinil to control sleepiness and antidepressant
      medications or sodium oxybate to control cataplexy. Modafinil and sodium oxybate
      have been developed and approved specifically for the indication of narcolepsy
      based on large, double-blind, placebo-controlled, parallel group efficacy and
      safety studies. The efficacy of drugs in the treatment of narcolepsy is variable
      from patient to patient and usually associated with adverse effects that can
      limit patient compliance and, therefore, symptom control. Nevertheless, the
      benefits of pharmacotherapy are judged to outweigh the risks to the patient. The
      favourable benefit-risk ratio of pharmacotherapy is greater if one considers the
      reduced risk to society of vehicle crashes and workplace mishaps that might be
      precipitated by attentional lapses or sleep attacks in the untreated or under
      treated patient with narcolepsy.

PMID- 12222991
TI  - Comparison of losartan with ACE inhibitors and dihydropyridine calcium channel
      antagonists: a pilot study of prescription-event monitoring in Japan.
AB  - INTRODUCTION: Two pilot studies for prescription-event monitoring in Japan (J
      PEM) were launched in 1997 and 1998. Here we present data regarding adverse
      events that were reported in the second pilot J-PEM study where losartan was
      compared with ACE inhibitors and dihydropyridine calcium channel antagonists.
      STUDY DESIGN: We conducted a cohort study with a concurrent control.
      METHODS/PATIENT GROUP: Study subjects prescribed losartan, an ACE inhibitor or a
      calcium channel antagonist were identified from prescriptions in hospital or
      community pharmacies. Events and other information were collected from doctors
      and pharmacists by mailed questionnaires. Events were coded and analysed using
      the Medical Dictionary for Regulatory Activities (MedDRA) terminology. Crude
      event rates were calculated and compared between patients treated with losartan
      and those receiving control drugs. When the difference was statistically
      significant, the event was further examined in several ways, including follow-up
      studies and by comparison with the data of the UK PEM study on losartan. RESULTS:
      Pharmacists were sent 4344 questionnaires and returned 3591 (83%), while doctors
      were sent 3517 questionnaires and returned 1380 (39%). In the doctors' data, the
      adverse event rate for losartan treatment was greater than that for ACE
      inhibitors and/or calcium channel antagonists for the following seven events:
      headache, palpitations, anaemia, insomnia, feeling abnormal, increased blood
      pressure and asthma. Most of these are known adverse drug reactions (ADRs) of
      losartan except for two events: increased blood pressure and asthma. In
      pharmacists' data, the event rate for losartan was significantly greater than
      that for control drugs for the following ten events: hot flushes, abnormal
      hepatic function, oedema, peripheral swelling, decreased blood pressure,
      increased blood pressure, rhinitis, contact dermatitis, dry skin and heat rash.
      The first five events were known ADRs of losartan but the other five were not.
      When the two sets of data were combined, the rate of an additional event,
      increased blood creatinine phosphokinase, which is a known ADR of losartan, was
      significantly greater than that for the control drugs. The six events that were
      not documented as ADRs for losartan were not judged to be ADRs based on the
      results of follow-up studies and comparison with the UK PEM study on losartan.
      The crude rate of cough with losartan treatment was similar to that with calcium
      channel antagonists, but was significantly less than that with ACE inhibitors.
      CONCLUSION: No novel safety problems were found in this observational cohort
      study on losartan. The rates of some known ADRs differed significantly between
      patients treated with losartan and those in the control groups.

PMID- 12222992
TI  - Incidence of herb-induced aconitine poisoning in Hong Kong: impact of publicity
      measures to promote awareness among the herbalists and the public.
AB  - BACKGROUND: In Hong Kong 'chuanwu' (the main root of Aconitum carmichaeli) and
      'caowu' (the root of Aconitum kusnezoffii) are used by herbalists to treat
      patients with various musculoskeletal disorders. These aconite roots contain
      aconitine, mesaconitine and hypaconitine, which are neurotoxins and cardiotoxins.
      During 1989 to 1991, 31 patients were treated in public hospitals because of
      poisoning by aconite roots and there were two deaths from ventricular
      arrhythmias. In late 1991, healthcare officials together with cardiologists held
      a press conference to warn the public, healthcare professionals and herbalists of
      the potential toxicity of aconite roots. The risk of ventricular arrhythmias and
      the need for urgent medical attention were highlighted. An information leaflet
      was also sent to hospital doctors. Since 1992, the topic was covered periodically
      in the local newspapers, medical journals and continuing medical education
      programmes. OBJECTIVE: The objective of this study was to assess the impact of
      these publicity measures on the incidence of herb-induced aconitine poisoning in
      the New Territories East, based on the number of admissions to the Prince of
      Wales Hospital. METHODS: During 1989 to 1993 and 1996 to 1998, all patients
      admitted to our medical wards because of herb-induced aconitine poisoning were
      identified by on-going surveillance of medical patients, searching our
      computerised medical record system and reviewing reports received by the 24-hour
      Drug and Poisons Information Bureau. RESULTS: The number of hospitalisations due
      to aconitine poisoning markedly decreased from four to six per year in 1989 to
      1991 to one to two per year in 1992 to 1993. The annual incidence of aconitine
      poisoning showed a marked decrease from 0.49 to 0.69 [overall 0.60, 95%
      confidence intervals (CI) 0.34 to 0.99] to 0.10 to 0.22 (overall 0.16, 95% CI
      0.03 to 0.46) per 100,000 population (p = 0.024). During 1996 to 1998, herb
      induced aconitine poisoning remained uncommon, with zero to two hospital
      admissions per year or an annual incidence of zero to 0.33 (overall 0.17, 95% CI
      0.05 to 0.43) per 100,000 population (p = 0.016). DISCUSSION: It is possible that
      the herbalists could have used smaller doses of 'chuanwu' and 'caowu' than
      before. Patients could be more compliant with the instructions on how to prepare
      the herbal decoction at home. However, our experience suggested that publicity
      measures to promote awareness, among the herbalists and the public, may reduce
      the incidence of poisoning due to toxic herbs such as aconite roots.

PMID- 12222993
TI  - Virus-based gene delivery systems.
AB  - Within the past decade, gene therapy strategies have come to the forefront of
      novel therapeutics. Tremendous advances in vector technology along with deeper
      understandings of vector biology and the molecular mechanisms of disease have
      significantly advanced the field of human gene therapy. This manuscript will
      discuss the viral-based subset of current gene transfer vectors. In particular,
      the most established viral vectors to date, including parvovirus, adenovirus,
      retrovirus, lentivirus, and herpesvirus-based vectors, are described, as well as
      the current innovative improvements being made to each. From past experience, it
      has become evident that in addition to optimising the vectors in terms of
      transgene expression, minimising vector-related immunology, and vector
      production, methods of vector delivery resulting in optimum vector transduction
      of target cells need to be established. This review will also illustrate several
      current improved physical delivery systems for optimal vector administration.

PMID- 12222996
TI  - Pharmacokinetics of omeprazole given by continuous intravenous infusion to
      patients with varying degrees of hepatic dysfunction.
AB  - OBJECTIVE: To examine the pharmacokinetics of omeprazole during intravenous
      infusion in patients with varying degrees of liver dysfunction (Child-Pugh
      categories A to C). DESIGN: Nonblinded single-period study. PATIENTS: Thirteen
      patients, five males and eight females with a mean age of 59 years and proven
      hepatic cirrhosis, classified according to Child-Pugh criteria as A (n = 5), B (n
      = 4) or C (n = 4). METHODS: Each patient received an 80mg bolus of omeprazole
      over 30 minutes followed by a continuous infusion of 8 mg/h for 47.5 hours. Blood
      samples were taken frequently throughout the infusion and during the subsequent
      24-hour washout period for determination of omeprazole and its metabolites.
      Laboratory screening was also performed at the start of the study, after 72 hours
      and at the 14 day follow-up visit. RESULTS: Data were evaluable for 12 patients.
      For omeprazole, the mean total area under the plasma concentration-time curve
      (AUC) was 286.5 micromol x h/L, peak plasma concentration was 14.9 micromol/L and
      terminal elimination half-life was 4.1 hours; these values were higher than those
      observed historically in control patient populations. Concentrations of the
      metabolite omeprazole sulphone were also increased, but there was a decrease in
      concentrations of hydroxy-omeprazole. Deviations from normal values increased
      with increasing disease severity for all parameters. For example, in patients
      with liver dysfunction of Child-Pugh categories A, B and C, AUC(48 )was 240.8,
      280.4 and 323.3 micromol x h/L compared with 151.3 micromol x h/L in the
      historical control population. Despite its altered pharmacokinetics, omeprazole
      was not associated with any serious or untoward effects. CONCLUSION: Exposure to
      omeprazole following intravenous administration was higher in patients with liver
      dysfunction than in the normal population. However, even in patients with
      severely impaired liver function, the omeprazole plasma concentration did not
      change by more than 100% and the drug was well tolerated.

PMID- 12222997
TI  - Heme oxygenase-1 genotype is a vascular anti-inflammatory factor following
      balloon angioplasty.
AB  - PURPOSE: To investigate the association of the heme oxygenase-1 (HO-1) genotype,
      which has potent anti-inflammatory capability, and the inflammatory response
      induced by balloon angioplasty. METHODS: Three hundred seventeen patients (188
      men; median age 70 years, range 57-77) undergoing femoropopliteal balloon
      angioplasty (n=150) or stenting (n=61) were evaluated for upregulation of the HO
      1 genotype; 106 patients undergoing lower limb angiography served as controls.
      The acute phase reactants C-reactive protein (CRP), serum amyloid A (SAA), and
      fibrinogen were measured 24 and 48 hours postintervention and compared to
      baseline values. An association of the relative increase (Delta, %) of these
      inflammatory markers with short (<25) (GT)(n) dinucleotide repeats in the HO-1
      gene promoter was assessed. RESULTS: The HO-1 genotype was significantly
      associated with Delta CRP(24) (p<0.0001), Delta CRP(48) (p<0.0001), Delta SAA(24)
      (p=0.02), and Delta SAA(48) (p=0.006) after balloon angioplasty; Delta fibrinogen
      showed no association. Patients with a higher Delta CRP(48) after balloon
      angioplasty exhibited significantly reduced odds for the presence of short (<25)
      (GT)(n) repeats. The adjusted odds reduction in the multivariate model was 80%
      (p=0.002) in the third quartile of Delta CRP(48) values and 90% (p=0.001) in the
      fourth quartile. No association of HO-1 genotype and inflammatory response was
      found 24 and 48 hours after stenting (p=0.3, p=0.5) or angiography (p=0.2,
      p=0.6). CONCLUSIONS: The HO-1 promoter genotype is independently associated with
      the inflammatory response seen after balloon angioplasty. Short alleles (<25 GT
      repeats) seem to be an intrinsic vascular anti-inflammatory factor.

PMID- 12222998
TI  - Rheolytic thrombectomy in the management of limb ischemia: 30-day results from a
      multicenter registry.
AB  - PURPOSE: To evaluate the use of rheolytic thrombectomy (RT) with the AngioJet
      catheter for treatment of lower extremity ischemia due to arterial/graft
      thrombotic occlusion. METHODS: A retrospective multicenter review was performed
      of 99 consecutive patients (52 men; mean age 67 +/- 13 years, range 30-90) who
      underwent RT for thrombotic occlusions in native arteries (n=80) or bypass grafts
      (n=19). Pre- and postprocedural limb ischemia and in-hospital events were
      evaluated. Amputation and mortality rates at 30 days were determined. RESULTS:
      The majority of patients (78.8%) presented within 14 days of symptom onset. RT
      resulted in substantial to complete thrombus removal in 70 (70.7%) patients and
      partial in 22 (22.2%); there was no angiographic change in 7 (7.1%). Adjunctive
      post RT thrombolysis was used in 37 patients. Underlying stenoses found in 81
      limbs were treated with one or more of the following procedures: balloon
      angioplasty (n=62), stenting (n=35), or nonemergent surgical revision (n=5). In
      hospital complications included 2 major amputations, 5 cases of minor tissue
      loss, 7 rethromboses, and 3 cases of transient renal insufficiency. Four (4.0%
      patients died in-hospital; the 95 surviving patients all had viable limbs at
      discharge. Mortality and amputation rates at 30 days were 7.1% and 4.0%,
      respectively. CONCLUSIONS: Percutaneous treatment of thrombotic occlusions with
      RT, followed by definitive treatment of the underlying stenosis, is a promising
      therapeutic option for patients with limb-threatening ischemia.

PMID- 12222999
TI  - Balloon angioplasty in chronic critical limb ischemia: factors affecting clinical
      and angiographic outcome.
AB  - PURPOSE: To assess factors that affect clinical and angiographic outcome in
      chronic critical limb ischemia (CLI) 12 months after primary, technically
      successful balloon angioplasty (BA) in infrainguinal arteries. METHODS: Sixty
      consecutive patients (37 women; mean age 75 +/- 10 years, range 53-99) with
      technically successful BA in 66 limbs were followed for 12 months or until death,
      for major amputation, or repeat target lesion revascularization (TLR). Assessment
      at baseline and 1 day and 12 months after BA or at an endpoint event, if
      feasible, was performed with angiography or duplex ultrasound (above-knee
      revascularization only). Mortality, limb prognosis, and restenosis rate were
      correlated with cardiovascular risk factors, hemodynamic measures, and
      angiographic features. RESULTS: Mortality was 25% at 1 year; compared to
      survivors, nonsurvivors more often had coronary artery disease (93% versus 44%
      for survivors, p<0.001), bilateral CLI (60% versus 29%, p=0.033), and higher
      fibrinogen levels (5.1 g/L versus 4.3 g/L, p=0.049). CLI resolved in more than
      half (35, 53%) of the limbs without repeat TLR. The major amputation rate was 6%.
      Limb prognosis correlated with ankle pressures after BA. Restenosis rates were
      65% at the femoropopliteal and 56% at the infrapopliteal level (NS); these
      correlated with the length of the treated arterial segment (8.7 cm with
      restenosis versus 4.0 cm without, p<0.001). CONCLUSIONS: High mortality in CLI
      was associated with an extensive, clinically manifest arteriosclerotic process
      and high fibrinogen levels. Limb prognosis and restenosis after BA were primarily
      influenced by local hemodynamic and technical factors. Despite considerable
      restenosis, more than 90% of survivors avoided major amputations.

PMID- 12223001
TI  - Arterial perforation during infrainguinal lower limb angioplasty does not worsen
      outcome: results from 1409 patients.
AB  - PURPOSE: To assess the prevalence and clinical significance of arterial
      perforation during lower limb angioplasty and determine the outcome of patients
      suffering this complication. METHODS: The radiology department records of 1409
      patients (878 men; mean age 69.6 years) undergoing peripheral angioplasty in 1532
      limbs between January 1996 and December 1998 were studied to identify patients
      with a perforated vessel. RESULTS: Fifty-two (3.7%) perforations occurred.
      Patients with a perforation were significantly older (median 74.8 years versus
      69.6, p=0.03) and were more likely to be diabetic (p=0.01). The median age of a
      smoker with a perforation was 68 years versus 78 years for nonsmokers (p=0.02).
      Among the perforations, 29 resolved without intervention, 6 required temporary
      balloon occlusion, 15 were coil embolized, and 2 needed both balloon and coil
      treatment. Twenty-four (46%) of the 52 patients had a clinically successful
      angioplasty despite the perforation. No patient needed further urgent
      intervention. Seven patients underwent subsequent surgery to treat the underlying
      vascular disease that had prompted treatment initially; no one was treated for
      complications of the perforation. Due to the more extensive nature of the
      procedure, subintimal angioplasty was associated with an unsurprising increase in
      the rate of perforation (RR, 2.06; 95% CI, 1.19-3.56; p=0.01). In no case did the
      perforation prejudice the eventual outcome of the patient. CONCLUSIONS: Arterial
      perforation during angioplasty is more common in the elderly and in diabetics.
      The perforation itself does not influence the ultimate outcome of the case;
      rather, it is the underlying vascular pathology.

PMID- 12223000
TI  - Subintimal angioplasty of isolated infragenicular vessels in lower limb ischemia:
      long-term results.
AB  - PURPOSE: To assess the outcome of subintimal angioplasty in treating isolated
      infragenicular arterial disease in patients with severe lower limb ischemia.
      METHODS: A retrospective study reviewed 67 consecutive patients (39 men; mean age
      76 years, range 41-96) who underwent infragenicular subintimal angioplasty
      between March 1997 and May 2000 for ischemia in 70 limbs. The median length of
      occlusion was 6 cm [corrected] (range 1-10) in the below-knee popliteal arteries,
      4 cm [corrected] (range 1-4) in the tibioperoneal trunk, 21 cm [corrected] (range
      1-35) in the anterior tibial artery, 10 (1-30) in the posterior tibial artery,
      and 5 (range 1-20) in the peroneal artery. RESULTS: The technical and clinical
      success rates were 86% and 80%, respectively. In the 10 (14%) patients with a
      technical failure, 3 underwent successful bypass, 4 had an amputation, 1 had a
      lumbar sympathectomy, and 2 were treated conservatively. Of the 4 (6%) limbs that
      did not achieve clinical success, 2 patients required femorodistal bypass and
      their ulcers improved; in the other 2, ulcerations did not heal completely. The
      cumulative limb salvage rate and freedom from critical limb ischemia (CLI)
      quantified by Kaplan-Meier life-table analysis were 94% and 84% at 36 months.
      Mortality rates were 19% at 1 year, 43% at 2 years, and 51% at 3 years. In a
      subgroup analysis, the rate of CLI was significantly lower in nondiabetics (4%)
      and than in diabetics (24%, p=0.02), but neither survival nor amputation rates
      were significantly different. CONCLUSIONS: Subintimal angioplasty is a safe and
      effective procedure for treating isolated crural vessels in patients with severe
      lower limb ischemia.

PMID- 12223002
TI  - Midterm follow-up of balloon-expandable ePTFE endografts in the femoropopliteal
      segment.
AB  - PURPOSE: To evaluate the midterm clinical outcome of patients treated with a
      balloon-expandable polytetrafluoroethylene (ePTFE) endograft for long-segment
      occlusive disease of the femoropopliteal segment. METHODS: Eighty-nine patients
      (68 men; median age 69 years, range 43-81) with disabling claudication (n=73) or
      critical ischemia (n=16) were treated with an ePTFE endograft (mean length 29 cm)
      for 7 stenosis (mean length 9 cm) and 82 occlusions (mean length 19 cm) in the
      femoropopliteal segment. The follow-up protocol included Doppler ankle-brachial
      pressure measurement and duplex scanning or angiography of the endograft at 6
      month intervals. Primary and secondary patency rates were analyzed. RESULTS: At
      the last examination, the endograft was patent in 52 patients (median 17 months,
      range 7-50) and occluded in 35 (median 7 months, range 0-40); 2 patients died of
      nonvascular causes with a patent endograft at 6.5 and 7 months. At follow-up, the
      primary and secondary endograft patency rates were 71% and 83% at 6 months, 57%
      and 69% at 1 year, 45% and 49% at 2 years, and 30% and 44% at 3 years,
      respectively. CONCLUSIONS: The midterm success of this new ePTFE endograft is
      limited; therefore, the device needs to be refined if this minimally invasive
      technique is to compete with conventional bypass surgery.

PMID- 12223003
TI  - Eligibility rates of ruptured and symptomatic AAA for endovascular repair.
AB  - PURPOSE: To determine the anatomical eligibility rate for endovascular repair of
      ruptured and symptomatic abdominal aortic aneurysms (AAA) using commercially
      available endografts. METHODS: In a retrospective review, 28 preoperative
      computed tomographic (CT) scans were examined from among 83 patients who
      underwent surgical repair of a ruptured or acutely symptomatic AAA at a
      university-based tertiary care center during the past 10 years. The proximal
      aortic neck, aneurysm, and iliac dimensions were compared to corresponding
      measurements from 100 preoperative CT scans from patients who underwent elective
      repair of asymptomatic AAA. Based on expanded selection criteria for the 2 FDA
      approved endografts (AneuRx and Ancure), eligibility rates for endovascular
      repair were compared between patients with ruptured/symptomatic and asymptomatic
      AAAs. RESULTS: The proximal neck of the ruptured/symptomatic AAAs was on the
      average 2 mm larger in diameter (25 +/- 4 versus 23 +/- 3 mm, p=0.04) and 7 mm
      shorter (16 +/- 10 versus 23 +/- 14, p=0.017) than asymptomatic AAAs. The maximum
      AAA diameter was significantly larger in the ruptured/symptomatic group (64 +/-
      16 mm) than in the asymptomatic group (58 +/- 11 mm, p=0.033). Of the 28
      ruptured/symptomatic AAAs assessed morphologically, 13 (46%) were anatomically
      eligible for endovascular repair compared to 74 of the 100 asymptomatic AAAs
      (p=0.006). The main cause for exclusion was an unfavorable proximal neck, which
      was present in 15 (54%) of the 28 ruptured/symptomatic AAAs and in 24 (24%) of
      the 100 asymptomatic AAAs (p=0.003). CONCLUSIONS: A significantly smaller
      proportion of patients presenting with ruptured/symptomatic AAA are anatomically
      eligible for endovascular AAA repair compared to patients with asymptomatic AAA
      due to unfavorable proximal neck anatomy.

PMID- 12222994
TI  - Clinical significance of the cytochrome P450 2C19 genetic polymorphism.
AB  - Cytochrome P450 2C19 (CYP2C19) is the main (or partial) cause for large
      differences in the pharmacokinetics of a number of clinically important drugs. On
      the basis of their ability to metabolise (S)-mephenytoin or other CYP2C19
      substrates, individuals can be classified as extensive metabolisers (EMs) or poor
      metabolisers (PMs). Eight variant alleles (CYP2C19*2 to CYP2C19*8) that predict
      PMs have been identified. The distribution of EM and PM genotypes and phenotypes
      shows wide interethnic differences. Nongenetic factors such as enzyme inhibition
      and induction, old age and liver cirrhosis can also modulate CYP2C19 activity. In
      EMs, approximately 80% of doses of the proton pump inhibitors (PPIs) omeprazole,
      lansoprazole and pantoprazole seem to be cleared by CYP2C19, whereas CYP3A is
      more important in PMs. Five-fold higher exposure to these drugs is observed in
      PMs than in EMs of CYP2C19, and further increases occur during inhibition of
      CYP3A-catalysed alternative metabolic pathways in PMs. As a result, PMs of
      CYP2C19 experience more effective acid suppression and better healing of duodenal
      and gastric ulcers during treatment with omeprazole and lansoprazole compared
      with EMs. The pharmacoeconomic value of CYP2C19 genotyping remains unclear. Our
      calculations suggest that genotyping for CYP2C19 could save approximately 5000 US
      dollars for every 100 Asians tested, but none for Caucasian patients.
      Nevertheless, genotyping for the common alleles of CYP2C19 before initiating PPIs
      for the treatment of reflux disease and H. pylori infection is a cost effective
      tool to determine appropriate duration of treatment and dosage regimens. Altered
      CYP2C19 activity does not seem to increase the risk for adverse drug
      reactions/interactions of PPIs. Phenytoin plasma concentrations and toxicity have
      been shown to increase in patients taking inhibitors of CYP2C19 or who have
      variant alleles and, because of its narrow therapeutic range, genotyping of
      CYP2C19 in addition to CYP2C9 may be needed to optimise the dosage of phenytoin.
      Increased risk of toxicity of tricyclic antidepressants is likely in patients
      whose CYP2C19 and/or CYP2D6 activities are diminished. CYP2C19 is a major enzyme
      in proguanil activation to cycloguanil, but there are no clinical data that
      suggest that PMs of CYP2C19 are at a greater risk for failure of malaria
      prophylaxis or treatment. Diazepam clearance is clearly diminished in PMs or when
      inhibitors of CYP2C19 are coprescribed, but the clinical consequences are
      generally minimal. Finally, many studies have attempted to identify relationships
      between CYP2C19 genotype and phenotype and susceptibility to xenobiotic-induced
      disease, but none of these are compelling.

PMID- 12223004
TI  - Endovascular versus conventional open repair of acute abdominal aortic aneurysm:
      feasibility and preliminary results.
AB  - PURPOSE: To evaluate the feasibility of endovascular treatment of acute abdominal
      aortic aneurysm (AAA) with commercially prepared bifurcated systems. METHODS:
      From January through July 2001, 22 patients (17 men; mean age 73.6 years, range
      59-89) were referred with an acute (symptomatic/ruptured) AAA. Six patients were
      treated with emergent open surgery because of hemodynamic instability, but the
      other 16 patients underwent computed tomographic angiography with
      multidirectional reconstruction. Six (27%) aneurysms were suitable for
      endovascular repair (EVR) and were successfully treated. Procedural variables,
      morbidity, and mortality were compared between the EVR group and 6 patients of
      equivalent hemodynamic status from among the conventionally treated patients.
      RESULTS: There was no mortality in either group. The median aneurysm diameter in
      the EVR group was 63 mm (range 48-84) versus 80 mm (45-82) in the matched
      surgically treated AAAs (p=0.628). Procedural duration was 193 minutes (150-265)
      for the EVR group compared to 203 minutes (130-270) for the matched group
      (p=0.630). Median blood loss was significantly less (p=0.010) in the EVR group
      (125 versus 3400 mL). Median length of stay (LOS) in intensive care was 8 hours
      (0-21) versus 62 hours (48-112) for the surgical group (p=0.004). Hospital LOS
      was significantly reduced (p=0.024) for the EVR patients (7.5 [2-16] versus 15.5
      [10-34] days). CONCLUSIONS: Endovascular treatment of acute aneurysm is feasible,
      and preliminary results are promising.

PMID- 12223006
TI  - Does fresh clot shrink faster than preexistent mural thrombus after endovascular
      AAA repair?
AB  - PURPOSE: To correlate the amount of preexistent thrombus in abdominal aortic
      aneurysms (AAA) to sac shrinkage after endovascular repair. METHODS: From January
      1993 through April 2000, 76 patients underwent endovascular AAA repair and were
      examined at 12 months to identify aneurysms that had decreased in size by > or =
      10%. Volume measurements were performed using a standardized spiral computed
      tomographic angiography (CTA) protocol with 3-dimensional postprocessing. Volume
      measurements were unavailable or incomplete in 16 patients, and another 16 did
      not have sac shrinkage > or = 10%, leaving 44 patients in the study group. The
      percentage of preexistent mural thrombus in shrinking sacs (OldThr%) was
      calculated by dividing the preoperative thrombus volume by the postoperative
      nonluminal thrombus volume. The 12-month volume change, expressed as a percentage
      of the postoperative thrombus volume and as an absolute value, was correlated
      with OldThr% using the Pearson product moment test. RESULTS: The median
      proportional shrinkage at 12 months was 56% (range 15%-89%) and the absolute
      nonluminal thrombus volume shrinkage was 49 mL (range 6-186). The median OldThr%
      was 53% (range 6%-94%). The correlation coefficients of OldThr% were 0.130
      (p=0.40) with the proportional shrinkage in thrombus volume and 0.235 (p=0.13)
      with the absolute volume change. CONCLUSIONS: The rate of shrinkage of
      successfully excluded aneurysm sacs after endovascular repair is independent of
      the preoperative mural thrombus volume in the aneurysm. Other factors are
      responsible for the large variation in shrinkage.

PMID- 12223005
TI  - Emergency treatment of symptomatic or ruptured abdominal aortic aneurysms: the
      role of endovascular repair.
AB  - PURPOSE: To report the initial experience with endovascular aortic repair (EVAR)
      in patients with ruptured or symptomatic abdominal aortic aneurysms (AAA) and to
      compare the results with conventional open surgery. METHODS: Between May 1999 and
      December 2001, 24 patients (21 men; mean age 75 years, range 56-89) with ruptured
      or symptomatic AAA underwent EVAR using a specially designed aortomonoiliac
      endograft. Six patients were selected based on device and operator availability;
      the subsequent 18 patients were treated under a modified management protocol that
      offered stent-graft repair to all symptomatic AAA patients. The results of this
      new treatment protocol were analyzed on an intention-to-treat basis for the last
      8 months of the study. The 30-day outcomes in all patients treated with emergency
      EVAR were compared with 40 consecutive, contemporaneous patients undergoing open
      surgery for symptomatic or ruptured AAA. RESULTS: No early conversions to open
      surgery were performed. Significantly decreased operative blood loss and
      intensive care stay (p<0.05 for both) were observed in EVAR patients. The
      mortality rate for EVAR patients was 17% compared to 32% in conventionally
      treated patients (NS). Among patients with ruptured AAA, the 30-day mortality
      rates were 24% (4/17) and 41% (12/29) for EVAR and open surgery, respectively
      (NS). Of 26 unselected patients who were treated prospectively under the modified
      protocol, the majority (81%, 21/26) had anatomy suitable for endovascular repair;
      however, only 18 (69%) underwent EVAR owing to a short infrarenal neck (n=2) or
      device/operator unavailability (n=6). CONCLUSIONS: EVAR is a feasible treatment
      in the majority of patients with ruptured or symptomatic AAA. The 30-day
      mortality appears to be similar between conventionally treated patients and those
      undergoing endovascular repair.

PMID- 12223007
TI  - The AneuRx stent-graft since FDA approval: single-center experience of 230 cases.
AB  - PURPOSE: To compare a single-center experience with the AneuRx stent-graft system
      before and after FDA approval to results from the multicenter phase II clinical
      trial. METHODS: The medical records of 230 consecutive patients (218 men; mean
      age 74 years) undergoing AneuRx stent-graft implantation for abdominal aortic
      aneurysm (AAA) exclusion since September 1999 were reviewed to collect patient
      characteristics, aneurysm morphology, procedure variables, perioperative
      morbidity, mortality, and short-term outcome. These data were compared to the 30
      patients treated at our institution during the AneuRx phase II clinical trial and
      to the overall multicenter trial data. Stent-graft difficulty was categorized
      from 1 (straight neck and access of appropriate size) to 4 (proximal neck <10 mm
      long or angulated >60 degrees and/or difficult access) based on aneurysm
      morphology. RESULTS: Data from the 30 patients enrolled in the phase II trial at
      our institution were comparable in terms of patient characteristics and procedure
      variables to patients treated after FDA approval and to the multicenter data.
      However, the proportion of cases involving aneurysms with a more complex
      morphology (levels 3 and 4) rose 22% after FDA approval, reflecting a change in
      referral patterns. Our postoperative endoleak and morbidity rates increased
      nonsignificantly with respect to our own phase II experience (17% versus 6%, 18%
      versus 11%, respectively); however, they were not significantly different from
      the multicenter data. Reintervention was performed in 15 of 38 endoleak cases,
      mostly type I. Only 5 (2.1%) cases had a persistent endoleak at the time of
      discharge. CONCLUSIONS: Since FDA approval of the AneuRx device, our endovascular
      practice has changed toward the management of increasingly more complex AAAs.
      Although we are attempting more challenging cases, we are able to maintain
      similarly high short-term success rates while offering stent-grafting to an
      increasing number of patients. These results suggest that more patients may be
      candidates for endoluminal graft placement than determined by the clinical trial
      selection criteria, provided that strict surveillance and long-term follow-up is
      maintained.

PMID- 12222995
TI  - Ontogeny of hepatic and renal systemic clearance pathways in infants: part I.
AB  - Dramatic developmental changes in the physiological and biochemical processes
      that govern drug pharmacokinetics and pharmacodynamics occur during the first
      year of life. These changes may have significant consequences for the way infants
      respond to and deal with drugs. The ontogenesis of systemic clearance mechanisms
      is probably the most critical determinant of a pharmacological response in the
      developing infant. In recent years, advances in molecular techniques and an
      increased availability of fetal and infant tissues have afforded enhanced insight
      into the ontogeny of clearance mechanisms. Information from these studies is
      reviewed to highlight the dynamic and complex nature of developmental changes in
      clearance mechanisms in infants during the first year of life. Hepatic and renal
      elimination mechanisms constitute the two principal clearance pathways of the
      developing infant. Drug metabolising enzyme activity is primarily responsible for
      the hepatic clearance of many drugs. In general, when compared with adult
      activity levels normalised to amount of hepatic microsomal protein, hepatic
      cytochrome P450-mediated metabolism and the phase II reactions of
      glucuronidation, glutathione conjugation and acetylation are deficient in the
      neonate, but sulfate conjugation is an efficient pathway at birth. Parturition
      triggers the dramatic development of drug metabolising enzymes, and each enzyme
      demonstrates an independent rate and pattern of maturation. Marked
      interindividual variability is associated with their developmental expression,
      making the ontogenesis of hepatic metabolism a highly variable process. By the
      first year of life, most enzymes have matured to adult activity levels. When
      compared with adult values, renal clearance mechanisms are compromised at birth.
      Dramatic increases in renal function occur in the ensuing postpartum period, and
      by 6 months of age glomerular filtration rate normalised to bodyweight has
      approached adult values. Maturation of renal tubular functions exhibits a more
      protracted time course of development, resulting in a glomerulotubular imbalance.
      This imbalance exists until adult renal tubule function values are approached by
      1 year of age. The ontogeny of hepatic biliary and renal tubular transport
      processes and their impact on the elimination of drugs remain largely unknown.
      The summary of the current understanding of the ontogeny of individual pathways
      of hepatic and renal elimination presented in this review should serve as a basis
      for the continued accruement of age-specific information concerning the ontogeny
      of clearance mechanisms in infants. Such information can only help to improve the
      pharmacotherapeutic management of paediatric patients.

PMID- 12223008
TI  - Short-term results of endovascular AAA repair with the Excluder bifurcated stent
      graft.
AB  - PURPOSE: To evaluate the safety and efficacy of endovascular abdominal aortic
      aneurysm (AAA) repair with a commercial modular stent-graft. METHODS: Between
      February 1998 and May 2000, 66 consecutive patients (56 men; mean age 70 years,
      range 51-87) were recruited for a single-center study to examine the safety and
      efficacy of the Excluder stent-graft for endovascular AAA repair. The patients
      were predominantly asymptomatic (2 symptomatic) and categorized as ASA III or IV
      (62, 94%), with aneurysms that ranged from 35 to 89 mm in diameter (mean 56).
      Surveillance included clinical examination and computed tomographic aortography
      at discharge, 6 weeks, and at 6, 12, and 24 months. RESULTS: All endoprostheses
      were implanted as intended, but 1 patient succumbed to an intraprocedural
      brainstem infarction (1.5% 30-day mortality rate). The major and minor morbidity
      rates were 21% and 4.5%, respectively. Primary technical success at discharge was
      68% (45/66), largely as the result of a 30% (20/66) endoleak rate. The aneurysm
      exclusion rate at 30 days was 88%. During the mean 5.8-month follow-up, no device
      migration, limb kinking, aneurysm rupture, or limb thrombosis was observed.
      CONCLUSIONS: Endoluminal AAA repair with the bifurcated Excluder stent-graft is
      safe and efficacious in the short term. Longer surveillance will have to
      demonstrate if the excellent early results can be maintained over the years.

PMID- 12223009
TI  - Long-term results of endovascular AAA repair using a homemade aortomonoiliac PTFE
      device.
AB  - PURPOSE: To assess the long-term results of a homemade aortomonoiliac
      polytetrafluoroethylene (PTFE) device used for endovascular abdominal aortic
      aneurysm (AAA) repair. METHODS: A vascular audit database was interrogated to
      identify 58 consecutive AAA patients (all men; median age 73 years, range 56-88)
      who underwent aortomonoiliac stent-graft repair. AAAs were eligible for
      endovascular treatment if the infrarenal neck was > or = 15 mm long and < or = 28
      mm in diameter. RESULTS: Nine (15.5%) procedures failed, 8 during the procedure
      and 1 on the 7th postoperative day; 8(13.8%) patients were converted, but one was
      unfit for surgery. There was one intraprocedural stroke, and 3 (5.2%) patients
      died within 30 days. The primary success rate (no conversion or mortality) was
      79.3%. Over a median follow-up of 45 months (range 23-80), there were 3 (5.2%)
      graft occlusions, 1 kink requiring stent implantation, and 1 expanding sac
      without identifiable endoleak. There were 11 (19.0%) endoleaks in 10 patients, 9
      type I leaks (2 proximal) and 1 type II. One patient with a distal type I
      endoleak (treated) also exhibited a type III leak at 2 years, but the sac size
      had not increased. There was a 40% incidence of bilateral buttock claudication,
      which was serious in only 1 patient. The long-term survival rate by Kaplan-Meier
      life-table analysis was 57% at 4 years. CONCLUSIONS: Implantation of an
      aortomonoiliac PTFE device can be achieved with good primary success, and the
      stent-graft seems durable over the long term. Proximal type I endoleaks are rare,
      but distal endoleaks from the contralateral common iliac artery can be solved by
      using a different covered stent.

PMID- 12223010
TI  - A hybrid endovascular procedure to preserve internal iliac artery patency during
      endovascular repair of aortoiliac aneurysms.
AB  - PURPOSE: To demonstrate the feasibility of a hybrid endovascular procedure to
      preserve blood flow in the internal iliac arteries (IIA) during aortoiliac
      endografting. TECHNIQUE: When aneurysmal dilatation makes the distal neck in the
      common iliac artery (CIA) too short for an adequate seal, the CIA bifurcation is
      exposed via an extraperitoneal approach after endograft deployment. Via an
      arteriotomy in the CIA, the distal end of the stent-graft is sutured to the CIA
      bifurcation under direct vision to preserve IIA blood flow. This approach has
      been successful in preserving IIA blood flow in 5 of 7 endograft procedures; in
      the other 2, IIA occlusion was a predictable event. CONCLUSIONS: Direct suturing
      of an aortoiliac stent-graft to the CIA bifurcation via an extraperitoneal
      approach is a useful method of maintaining IIA perfusion. However, further study
      is required to identify patients at high risk of pelvic ischemia who would
      benefit from such intervention.

PMID- 12223011
TI  - Predictors for clinical success at one year following renal artery stent
      placement.
AB  - PURPOSE: To determine pretreatment variables that may predict 1-year clinical
      outcome of stent placement for renal artery stenosis. METHODS: In a prospective
      study, 40 consecutive patients (29 men; mean age 60 +/- 9.1 years) with
      angiographically proven atherosclerotic renal artery stenosis were treated with
      stent placement because of drug resistant hypertension (n=14), renal function
      impairment (n=14), or both (n=12). Clinical success at 1 year was defined as a
      decrease of diastolic blood pressure > or = 10 mmHg or a decrease in serum
      creatinine > or = 20%, depending on the indication for treatment. Regression
      analysis was performed using anatomical parameters from angiography and
      intravascular ultrasound, estimates of renal blood flow from renal scintigraphy,
      and single-kidney renal function measurements. RESULTS: Patients treated for
      hypertension had better outcome than those treated for renal function impairment,
      with clinical success rates of 85% and 35%, respectively. Preserved renal
      function, with low serum creatinine and high 2-kidney glomerular filtration rate
      at baseline, was associated with clinical success in the entire patient group at
      follow-up (p=0.02 and p=0.03, respectively). An elevated vein-to-artery renin
      ratio on the affected side was borderline predictive (p=0.06). In patients
      treated for renal impairment, lateralization to the affected kidney (affected
      kidney-to-2-kidney count ratio < or = 0.45) on the scintigram emerged as a
      significant predictor for clinical success, with an odds ratio of 15 (p=0.048).
      CONCLUSIONS: Clinical success of renal artery stent placement is better for the
      treatment of hypertension than for preserving renal function. In patients with
      renal function impairment, lateralization to the affected kidney on the
      scintigram appears to be a predictor of clinical success.

PMID- 12223012
TI  - Percutaneous inferior vena cava-to-portal vein shunt (PIPS) using a stent-graft:
      preliminary results.
AB  - PURPOSE: To present preliminary results of an inferior vena cava (IVC)-to-portal
      vein shunt (PIPS) that is created through the caudate lobe of the liver. METHODS:
      Sixteen patients (13 men; mean age 50 years, range 32-63) were referred for PIPS
      procedures because of bleeding varices (n = 11), intractable ascites (n = 4), and
      hepatorenal syndrome (n = 1). The severity of liver disease was Child's B in 2
      and Child's C in 14. The PIPS was created by a transhepatic puncture through the
      IVC and the portal vein; an endograft made of polytetrafluoroethylene sutured to
      a Palmaz stent was placed through a jugular approach. RESULTS: In 13 (81%)
      patients, the portal vein-to-IVC tracts were successfully created. The
      postprocedural portal vein-IVC gradients varied from 1 to 9 mm Hg (mean 5). There
      were 2 deaths in the 30-day periprocedural period from adult respiratory distress
      syndrome and hepatorenal syndrome. A third patient died at 31 days from liver
      failure owing to continuing alcohol abuse. In addition, there was 1 case of
      peritoneal bleeding treated with blood product replacement. The follow-up period
      ranged from 14 to 671 days (mean 343). None of the patients treated for variceal
      bleeding had another bleeding episode, but 2 patients who had a PIPS procedure
      for refractory ascites did not benefit from the procedure. Postprocedure, 46%
      (6/13) of the patients had hepatic encephalopathy, which was unchanged from
      baseline. The primary and secondary patency rates at 365 days were 60% and 65%,
      respectively. CONCLUSIONS: The preliminary results using a stent-graft to create
      an IVC-portal vein shunt are encouraging and support further work to better
      determine the role of this procedure.

PMID- 12223013
TI  - Contrast-enhanced 3D MRA of the aortoiliac and infrainguinal arteries when
      conventional transfemoral arteriography is not feasible.
AB  - PURPOSE: To evaluate whether contrast-enhanced 3-dimensional (3D) magnetic
      resonance angiography (MRA) can substitute for transaxillary or transbrachial
      catheter access when angiography via the transfemoral route is not possible.
      METHODS: Contrast-enhanced 3D MRA was performed in 14 patients (12 men; mean 66.1
      +/- 12.4 years, range 48-98) with atherosclerotic disease of the aorta or lower
      extremities in whom conventional transfemoral arteriography was not feasible. The
      images were evaluated for their ability to identify and characterize lesions
      directly responsible for the patient's symptoms, adequately depict the vascular
      anatomy for therapy planning, and identify additional lesions not directly
      responsible for the patient's symptoms. The arterial system was divided into 15
      segments, and image quality and the presence of occlusive disease were
      determined. RESULTS: MRA adequately depicted 387 (95%) of 406 arterial segments
      in 14 patients. Nineteen (5%) arterial segments were inadequately delineated
      because of low signal intensity distal from severe stenoses (n = 11), venous
      overlap (n = 6), or metallic clip-induced signal voids (n = 2). The lesions
      directly responsible for the patients' symptoms were identified in all 14
      patients (2 aortic occlusions [Leriche's syndrome] and 12 iliac occlusions or
      severe stenoses). Visualization of the vascular anatomy was adequate for therapy
      planning in 13 of 14 patients, and 3D MRA satisfactorily identified other lesions
      not directly responsible for the current symptoms. CONCLUSIONS: When transfemoral
      catheter angiography of the aortoiliac and lower extremities is not feasible,
      contrast-enhanced 3D MRA is suitable for determining and planning therapy and can
      be used instead of angiography via the transaxillary or transbrachial routes.

PMID- 12223014
TI  - Computerized modeling based on spiral CT data for noninvasive determination of
      aortic stent-graft length.
AB  - PURPOSE: To preprocedurally determine the correct length of a nonbifurcated
      endovascular prosthesis for abdominal aortic aneurysm (AAA) repair using a
      computerized model. METHODS: A computer program was implemented to calculate the
      optimal intraluminal course of nonbifurcated stent-grafts from spiral computed
      tomographic (CT) images of the aortic lumen reconstructed at 2.5, 5, and 10-mm
      slice thicknesses. The algorithm was tested using 10 phantoms fabricated from 150
      mm-long, 10-mm-diameter copper rods that were bent into shapes mimicking
      different aortic configurations. Midpoint coordinates and rod diameters were
      determined from each CT image by 3 independent observers and served as input
      parameters to the program. The influence of the different CT reconstructions on
      the calculated lengths and possible observer dependence were assessed using
      calculated length estimation errors. Spiral CT images from 20 consecutive AAA
      patients scanned before stent-graft implantation were also processed to evaluate
      the algorithm under clinical conditions. RESULTS: Length estimation errors of the
      phantoms depended on the degree of bending as well as on the CT reconstruction
      slice thickness but were observer independent. Maximum errors were 7% for the 10
      mm slices, 3.5% for the 5-mm slices, and 1.2% for a 2.5-mm reconstruction. The
      mean longitudinal shortening of the aorta due to vessel tortuosity was 9.1% +/-
      4.8% among the 20 patients. Based on the results of the phantom study, errors of
      the calculated stent-graft lengths in patients were estimated to be approximately
      1% for a 5-mm CT reconstruction increment and <2% for a 10-mm increment.
      CONCLUSIONS: The proposed algorithm makes it possible to calculate noninvasively
      the correct length of straight stent-grafts under clinical conditions with a 1%
      to 2% error.

PMID- 12223015
TI  - Virtual angioscopy using 3-dimensional rotational digital subtraction angiography
      for endovascular assessment.
AB  - PURPOSE: To investigate the feasibility of 3-dimensional rotational digital
      subtraction angiography (3D DSA) and the creation of virtual angioscopic images
      from its data before and after endovascular treatment. TECHNIQUE: Data sets from
      3D DSA studies were used to create intraluminal images simulating angioscopy for
      36 patients with arterial stenosis, aneurysm, or endoleak after stent-graft
      deployment. A biplanar DSA unit was used to acquire rotational angiography data,
      which was then processed with a surface-rendering technique to create maximum
      intensity projections, shaded surface displays, multiplanar reconstructions, and
      virtual angioscopy. 3D reconstructions were created in 2 minutes after
      angiography and provided realistic views adequate for vessel measurement,
      morphology assessment, and endoleak evaluation. CONCLUSIONS: 3D DSA and virtual
      angioscopy are novel techniques that have been successful in recreating images of
      blood vessels immediately after angiography. These techniques could be useful as
      additional imaging modalities to complement computed tomography or magnetic
      resonance imaging in the evaluation of vascular diseases after endovascular
      therapy.

PMID- 12223016
TI  - Type III endoleak from a thoracic aortic stent-graft.
AB  - PURPOSE: To present an as yet unreported late complication of an Excluder
      thoracic endograft. CASE REPORT: A 78-year-old man underwent surgery for a
      ruptured type V thoracoabdominal aortic aneurysm in 1996. Four years later, an
      aneurysm was detected in the proximal thoracic aorta and repaired with 2 Excluder
      endoprostheses. At 12 months, computed tomography showed an increase in the
      aneurysm sac diameter and a type III endoleak, which was traced to a hole in the
      stent-graft fabric on arteriography. No fracture of the metal components was
      detected in the stent-grafts. Another Excluder device was implanted within the
      distal endograft. Satisfactory exclusion of the leak has been maintained for 6
      months. CONCLUSIONS: The risk of type III leaks must be minimized before stent
      grafting can be regarded as a routine procedure in the treatment of thoracic
      aortic aneurysms.

PMID- 12223017
TI  - Type II endoleak: transperitoneal sacotomy and ligation of side branch endoleaks
      responsible for aneurysm sac expansion.
AB  - PURPOSE: To demonstrate aneurysm sac expansion in the face of a type II endoleak
      and its treatment with open ligation of multiple side branch endoleaks. CASE
      REPORT: An 81-year-old patient had undergone elective endovascular repair of a
      6.3-cm infrarenal abdominal aortic aneurysm in September 1999. Routine spiral
      computed tomographic angiography at 10 months disclosed a type II endoleak; the
      aneurysm sac diameter had grown to 7.4 cm. Selective angiography revealed
      multiple lumbar endoleaks and a patent inferior mesenteric artery. Laparotomy and
      sacotomy was performed, confirming the presence of pulsatile type II endoleaks,
      which were ligated successfully. The patient made a full postoperative recovery.
      CONCLUSIONS: Type II endoleaks may cause aneurysm expansion. Open repair of
      multiple type II endoleaks is feasible and may be useful where endovascular or
      laparoscopic techniques are at high risk of procedural failure, such as multiple
      endoleak channels.

PMID- 12223018
TI  - Endovascular treatment and complete regression of an infected abdominal aortic
      aneurysm.
AB  - PURPOSE: To report a case of successful endovascular treatment of an infected
      abdominal aortic aneurysm (AAA) following Salmonella septicemia. CASE REPORT: A
      60-year-old man was admitted for rapid onset of urinary frequency, fever, and
      suprapubic pain extending to the flanks. Blood cultures were positive for
      Salmonella enteritidis, and appropriate antibiotic treatment was started. After 4
      weeks, fever ceased and the C-reactive protein fell to 5.8 mg/dL, but the
      erythrocyte sedimentation rate remained unchanged. Back pain prompted computed
      tomography, which showed a large AAA with a very irregular aortic wall suspicious
      of impending rupture. A tube stent-graft was introduced under general anesthesia
      from a left groin incision and deployed immediately below the renal arteries; a
      proximal type I endoleak was suspected but not repaired. Oral antibiotic therapy
      was continued for 2 months after discharge. By 6 months, the endoleak had sealed
      with a concomitant decrease in the maximal diameter of the aneurysm from 7.4 to
      5.6 cm. At 4 years, the aneurysm sac was no longer visible. CONCLUSIONS: Although
      experience is limited, endovascular grafting in combination with antibiotic
      therapy in selected infected aneurysms might represent an effective low-risk
      alternative to conventional surgery with the potential to restore normal vascular
      anatomy.

PMID- 12223019
TI  - Endovascular repair of a type B aortic dissection with transposition of a
      coexistent aberrant subclavian (lusorian) artery.
AB  - PURPOSE: To report the endovascular treatment of a relatively uncommon entity: an
      aortic type B dissection combined with an aberrant subclavian artery (SA). CASE
      REPORT: A 59-year-old patient was admitted with chest pain and interscapular back
      pain. A transesophageal ultrasound and magnetic resonance angiography revealed a
      type B aortic dissection originating at the level of an aberrant SA orifice.
      After failure of medical therapy, the dissection was treated by transluminal
      implantation of an Excluder stent-graft covering the entry site of the dissection
      at the aberrant SA orifice. Prior to the endovascular procedure, a transposition
      of the aberrant SA to the right carotid artery was performed through a
      supraclavicular approach. The patient remains asymptomatic at 19 months after the
      endovascular repair. CONCLUSIONS: Endovascular repair of a type B aortic
      dissection in the presence of a lusorian artery appears to be a feasible, safe,
      and less invasive alternative to conventional surgery. The need for concurrent
      transposition of the SA remains to be determined.

PMID- 12223020
TI  - Colonic infarction following endovascular AAA repair: a multifactorial
      complication.
AB  - PURPOSE: To report a case of colonic infarction following endovascular abdominal
      aortic aneurysm (AAA) repair in a patient with both internal iliac arteries (IIA)
      unobstructed by the endograft. CASE REPORT: A 73-year-old man presented with blue
      toes as a result of emboli from a 6.4-cm AAA. As he was medically at high risk
      for open repair and his aneurysm morphology was suitable for a modular bifurcated
      endovascular graft, a Zenith endograft was used to exclude the aneurysm. Twenty
      hours after the successful procedure, in which both IIAs were preserved, the
      patient regurgitated coffee-ground vomit; an upper gastrointestinal endoscopy
      found a small Mallory-Weiss tear and antral gastritis. A proton-pump inhibitor
      was begun, but his symptoms progressed. Laparotomy revealed transmural ischemia
      and infarction of the upper rectum, sigmoid, descending colon, and the splenic
      flexure; a colonic resection with formation of Hartmann's pouch and colostomy was
      performed. He made a slow but uncomplicated recovery. CONCLUSIONS: Colonic
      necrosis can complicate endovascular AAA repair even when both IIAs are
      preserved. Advantageously, the clinical signs of severe colonic ischemia in
      endograft patients are not obscured by aftereffects of a laparotomy.

PMID- 12223022
TI  - Neurology: then, now, and in the future.

PMID- 12223021
TI  - Explaining the cause of the amyloid burden in Alzheimer disease.

PMID- 12223023
TI  - Ion channels and neuronal dysfunction in multiple sclerosis.

PMID- 12223024
TI  - Beta-secretase protein and activity are increased in the neocortex in Alzheimer
      disease.
AB  - CONTEXT: Amyloid plaques, a major pathological feature of Alzheimer disease (AD),
      are composed of an internal fragment of amyloid precursor protein (APP): the 4-kd
      amyloid-beta protein (Abeta). The metabolic processing of APP that results in
      Abeta formation requires 2 enzymatic cleavage events, a gamma-secretase cleavage
      dependent on presenilin, and a beta-secretase cleavage by the aspartyl protease
      beta-site APP-cleaving enzyme (BACE). OBJECTIVE: To test the hypothesis that BACE
      protein and activity are increased in regions of the brain that develop amyloid
      plaques in AD. METHODS: We developed an antibody capture system to measure BACE
      protein level and BACE-specific beta-secretase activity in frontal, temporal, and
      cerebellar brain homogenates from 61 brains with AD and 33 control brains.
      RESULTS: In the brains with AD, BACE activity and protein were significantly
      increased (P<.001). Enzymatic activity increased by 63% in the temporal neocortex
      (P =.007) and 13% in the frontal neocortex (P =.003) in brains with AD, but not
      in the cerebellar cortex. Activity in the temporal neocortex increased with the
      duration of AD (P =.008) but did not correlate with enzyme-linked immunosorbent
      assay measures of insoluble Abeta in brains with AD. Protein level was increased
      by 14% in the frontal cortex of brains with AD (P =.004), with a trend toward a
      15% increase in BACE protein in the temporal cortex (P =.07) and no difference in
      the cerebellar cortex. Immunohistochemical analysis demonstrated that BACE
      immunoreactivity in the brain was predominantly neuronal and was found in tangle
      bearing neurons in AD. CONCLUSIONS: The BACE protein and activity levels are
      increased in brain regions affected by amyloid deposition and remain increased
      despite significant neuronal and synaptic loss in AD.

PMID- 12223025
TI  - Spontaneous "second wind" and glucose-induced second "second wind" in McArdle
      disease: oxidative mechanisms.
AB  - BACKGROUND: Blocked glycogen breakdown in McArdle disease impairs oxidative as
      well as anaerobic metabolism, but the contribution of impaired oxidative
      phosphorylation to everyday symptoms of McArdle disease remains poorly defined.
      OBJECTIVE: To evaluate the oxidative implications of the spontaneous second wind
      and variables that influence the development of this typical feature of McArdle
      disease. DESIGN: Assessment of exercise and oxidative capacity (.VO(2)) before
      and after the spontaneous "second wind" and with a glucose infusion after a
      spontaneous second wind. PATIENTS: Eight patients with complete myophosphorylase
      deficiency and 1 unique patient with 3% of normal myophosphorylase activity. MAIN
      OUTCOME MEASURES: Work capacity,.VO(2), heart rate, cardiac output. RESULTS: All
      patients with complete myophosphorylase deficiency (1) had low peak.VO(2) (mean
      +/- SD, 13.0 +/- 2.0 mL. kg(-1). min(-1)) in the first 6 to 8 minutes of
      exercise; (2) achieved a spontaneous second wind with increased exercise capacity
      between 8 and 12 minutes of exercise due to a more than 25% increase in
      peak.VO(2) (16.5 +/- 3.1 mL. kg(-1). min(-1)); and (3) with glucose infusion
      after a spontaneous second wind, experienced a further more than 20% increase in
      oxidative capacity (.VO(2), 19.9 +/- 3.9 mL. kg(-1). min(-1)). In the patient
      with residual myophosphorylase,.VO(2) (22.2 mL. kg(-1). min(-1)) in the first 6
      to 8 minutes of exercise was approximately 2-fold higher than the mean of
      patients lacking myophosphorylase, and no significant improvement in exercise and
      oxidative capacity accompanied prolonged exercise or glucose infusion.
      CONCLUSIONS: First, the spontaneous second wind and the glucose-induced second
      second wind in McArdle disease are due to substrate-dependent increases in muscle
      oxidative capacity. Second, by providing glycogen-derived pyruvate, a small
      amount of residual myophosphorylase activity normalizes the oxidative deficit of
      complete myophosphorylase deficiency and virtually eliminates the spontaneous
      second wind and glucose-induced second second wind.

PMID- 12223026
TI  - Assessment of normal-appearing white and gray matter in patients with primary
      progressive multiple sclerosis: a diffusion-tensor magnetic resonance imaging
      study.
AB  - BACKGROUND: Diffusion-tensor magnetic resonance imaging is sensitive to the more
      destructive aspects of multiple sclerosis (MS) evolution occurring outside and
      within T2-visible lesions and, as a consequence, holds promise for providing a
      more complete picture of primary progressive (PP) MS-related tissue damage than
      conventional magnetic resonance imaging. OBJECTIVE: To improve our understanding
      of PPMS by assessing the extent of occult pathological features in the normal
      appearing white and gray matter of the brain using diffusion-tensor magnetic
      resonance imaging. METHODS: Ninety-six patients with PPMS, 47 patients with
      secondary progressive (SP) MS, and 44 healthy control subjects were studied. T2
      hyperintense and T1-hypointense lesion volumes were calculated, and the volume of
      the whole brain tissue was measured. Diffusion-tensor magnetic resonance imaging
      scans were postprocessed and analyzed to obtain the mean diffusivity and
      fractional anisotropy histograms from the brain and from the normal-appearing
      white and gray matter in isolation. RESULTS: The mean T2-hyperintense and T1
      hypointense lesion volumes were lower in patients with PPMS than in patients with
      SPMS, while the mean absolute brain volumes were similar in the 2 groups. The
      average lesion diffusivity was significantly higher in patients with SPMS than in
      patients with PPMS (P<.001). Histogram-derived metrics of the brain tissue and
      normal-appearing white and gray matter were significantly different between
      patients with PPMS and healthy subjects (range, P =.004 to <.001). Average
      diffusivity values were significantly higher in patients with SPMS than in
      patients with PPMS for all the tissues studied (range, P =.001 to <.001).
      Fractional anisotropy histogram-derived quantities did not significantly differ
      between the 2 patient groups (range, P =.94 to.03). CONCLUSION: This study
      confirms that, in patients with PPMS, normal-appearing white and gray matter are
      not spared by disease-related pathological processes, although they are affected
      to a lesser degree than in patients with SPMS.

PMID- 12223027
TI  - Dementia in Parkinson disease: a proton magnetic resonance spectroscopy study.
AB  - BACKGROUND: Magnetic resonance spectroscopy has been shown to be useful in
      differentiating idiopathic Parkinson disease (PD) from atypical parkinsonian
      syndromes such as progressive supranuclear palsy, multiple system atrophy, and
      corticobasal degeneration. OBJECTIVE: To systematically investigate the utility
      of proton magnetic resonance spectroscopy in distinguishing between idiopathic PD
      with dementia (PDD) and without dementia. DESIGN: Group comparisons and
      correlations of brain metabolites with clinical and neuropsychological variables.
      PATIENTS AND METHODS: Metabolite concentrations were acquired from voxels
      localized to the basal ganglia and occipital cortex in 14 patients diagnosed as
      having idiopathic PDD, 12 patients with PD without dementia, and 13 matched
      control subjects. The 3 groups underwent clinical and neuropsychological
      assessment. RESULTS: In the occipital region, N-acetylaspartate levels were
      significantly reduced in the PDD group relative to the PD and control groups. N
      acetylaspartate values correlated with neuropsychological performance but not
      with severity of motor impairment. CONCLUSIONS: N-acetylaspartate reduction in
      occipital lobes may be a marker for dementia in PD. The distribution of
      metabolite reduction differs from that reported in Alzheimer disease. These
      findings suggest that proton spectroscopy may serve as a metabolic marker of
      cognitive disturbance in patients with PD.

PMID- 12223028
TI  - Encephalopathy and stroke after coronary artery bypass grafting: incidence,
      consequences, and prediction.
AB  - BACKGROUND: In contrast to perioperative stroke, much less attention has been
      paid to those with evidence of diffuse brain encephalopathy, presenting as
      delirium, confusion, coma, and seizures in the immediate postoperative period.
      OBJECTIVE: To determine the incidence, consequences, and predictive factors for
      encephalopathy and stroke following coronary artery bypass grafting. METHODS: In
      a prospective evaluation of 2711 patients operated on between January 1, 1997,
      and December 31, 2000, preoperative risk factors were obtained before surgery and
      postoperative outcomes, encephalopathy and stroke, were determined on a daily
      basis. All strokes were confirmed by neurologic consultation and, in most
      instances, by imaging. Logistic regression analyses were performed to determine
      risk factors for these outcomes. RESULTS: The incidence of encephalopathy was
      6.9% and of stroke, 2.7%. For patients without either of these outcomes, the
      average length of stay in the hospital was 6.6 days and the mortality was 1.4%.
      In contrast, patients with encephalopathy had a length of stay of 15.2 days and a
      mortality of 7.5%, and those with stroke, a length of stay of 17.5 days and a
      mortality of 22.0%. Predictive models were developed for encephalopathy involving
      5 preoperative factors (age, past stroke, carotid bruit, hypertension, and
      diabetes) and 1 perioperative factor (time on cardiopulmonary bypass). The model
      for stroke involved only 3 preoperative risk factors (past stroke, hypertension,
      and diabetes). CONCLUSIONS: Encephalopathy or stroke is associated with
      significant increases in length of stay and mortality after coronary artery
      bypass grafting. Patients at higher risk for these outcomes can be identified
      before surgery.

PMID- 12223030
TI  - Impairment of the peripheral nervous system in Creutzfeldt-Jakob disease.
AB  - BACKGROUND: The clinical manifestations of Creutzfeldt-Jakob disease (CJD)
      primarily reflect involvement of the central nervous system. The coexistence of
      CJD with peripheral nervous system involvement has also been reported. OBJECTIVE:
      To analyze peripheral neuron electrophysiologic changes and to compare these data
      with neuropathologic features of spinal motor neurons in patients with definite
      CJD. DESIGN AND PATIENTS: Electrophysiologic examinations were performed on 16
      patients with sporadic CJD. The diagnosis was confirmed by neuropathologic
      examinations (15 patients) or by intravital detection of the 14-3-3 protein in
      the cerebrospinal fluid (1 patient). The spinal cord was neuropathologically
      examined in 8 patients. SETTING: Department of Clinical Neurophysiology, I
      Neurological Department, Institute of Psychiatry and Neurology, Warsaw, Poland.
      MAIN OUTCOME MEASURES: Electromyography, compound muscle and sensory nerve action
      potentials, distal latencies, F waves, peripheral motor and sensory conduction
      velocity, and spinal motor neuron numbers and morphologic characteristics.
      RESULTS: All patients had signs of central nervous system damage typical of
      sporadic CJD. Only 3 patients had clinical signs of peripheral nervous system
      involvement. Electrophysiologic examinations confirmed peripheral nervous system
      damage in these patients and revealed preclinical peripheral nervous system
      impairment in 11 more patients. In 1 patient, electrophysiologic examination
      revealed features of motor neuron disease; in 9, axonal disease; and in 4, axonal
      demyelinating neuropathy. Neuropathologic examination results confirmed severe
      loss of spinal motor neurons in 1 patient with motor neuron disease and revealed
      the features of motor neuron chronic disease in 4. In 2 of them,
      electrophysiologic data were normal. CONCLUSION: In sporadic cases of CJD,
      peripheral nervous system impairment should be considered to be an integral
      component of disease.

PMID- 12223031
TI  - Electrocardiographic findings predict short-term cardiac morbidity after
      transient ischemic attack.
AB  - BACKGROUND: Current guidelines recommend the use of electrocardiography (ECG) in
      the evaluation of transient ischemic attack (TIA), but the data supporting its
      value in acute management are sparse. OBJECTIVE: To determine whether ECG
      findings are useful as independent predictors of short-term cardiac or neurologic
      complications after TIA. METHODS: We included patients who presented to 1 of 16
      emergency departments of a health maintenance organization in northern California
      and received a diagnosis of TIA from March 1, 1997, through February 28, 1998,
      for a 90-day follow-up. A cardiac event was defined as a hospitalization or a
      death due to myocardial infarction, ventricular arrhythmia, heart failure, or
      unstable angina. RESULTS: Among the 1327 patients with TIA for whom ECG findings
      were available for diagnostic coding, cardiac events occurred in 2.9%, strokes in
      10.9%, recurrent TIAs in 13.7%, and deaths in 2.6% during 90-day follow-up. The
      ECG findings disclosed a new diagnosis of atrial fibrillation in 28 (2.3%) of the
      1200 patients with no history of this condition. The 90-day risk for a cardiac
      event was greater in those who had any abnormal ECG findings (4.2% vs 0.6%;
      P<.001). This association remained significant after adjustment for medical
      history and examination findings (odds ratio, 6.9; 95% confidence interval, 1.6
      29.5; P =.009). Left ventricular hypertrophy, atrial fibrillation, and
      atrioventricular conduction abnormalities were each independently associated with
      more than doubling of the risk. The ECG abnormalities were not associated with
      risk for stroke or death. CONCLUSIONS: Short-term cardiac morbidity is
      substantial after TIA. Electrocardiographic findings disclose new atrial
      fibrillation in a significant portion of patients with TIA and can identify a
      group of patients at a substantially higher risk for short-term cardiac events.

PMID- 12223032
TI  - Outcome measures for pediatric spinal muscular atrophy.
AB  - BACKGROUND: Spinal muscular atrophy (SMA) is a genetic disease of the anterior
      horn cell with a frequency of 8 per 100 000 live births and a high rate of
      mortality during infancy. The American Spinal Muscular Atrophy Randomized Trials
      (AmSMART) Group is an organization of 5 centers formed to perform clinical trials
      in children with SMA. OBJECTIVE: To devise reliable methods to measure strength,
      motor function, lung function, and quality of life for use as outcome measures in
      children with SMA. SETTING: Tertiary referral center, pediatric neurology
      department. PATIENTS AND METHODS: Twelve children with SMA aged 2 to 14 years
      were enrolled in a reliability study of 4 outcome measures: quantitative muscle
      testing (in children >5 years), gross motor function measure, pulmonary function
      tests, and quality of life. The Richmond Quantitative Measurement System was used
      to test grip, knee flexion and extension, and elbow flexion. Gross motor function
      measure was performed as described, and pulmonary function tests were measured
      using the KoKo system. Quality of life was assessed via the PedsQL and the PedsQL
      Neuromuscular Module for patients and parents. RESULTS: Ten children fulfilled
      the inclusion criteria and completed at least 3 visits with 3 evaluators in 6
      months. Using a weighted kappa, the gross motor function measure showed high
      interrater reliability. Quantitative muscle testing showed greater variability
      among the weakest children; the findings for pulmonary function tests and quality
      of life were inconclusive. The PedsQL Neuromuscular Module for parents had
      moderately high reliability. CONCLUSION: A tool for motor function may be more
      useful in clinical trials of childhood SMA than one for quantitative muscle
      strength.

PMID- 12223033
TI  - Preservation of directly stimulated muscle strength in hemiplegia due to stroke.
AB  - BACKGROUND: Hemiplegia, or hemiparesis, severe impairment of purposeful
      activation of striated musculature, is the most conspicuous and often most
      disabling symptom of acute cerebrovascular lesions. Spontaneous improvement of
      voluntary strength may extend over many months. OBJECTIVE: In this archetypical
      upper motor neuron syndrome we wish to ascertain the degree of functional
      impairment due to direct contractile impairment of the affected striated
      musculature. DESIGN: Maximal tetanic muscle contraction was elicited by
      electrical stimulation applied directly to the tibialis anterior of the paretic
      and nonparetic limbs. Maximal forces of the normal limbs were compared with the
      afflicted limbs both early and late after vascular lesions of the pyramidal
      tract. Maximal voluntary force of foot dorsiflexion in the same limbs was also
      determined. Similar measurements were made in healthy control participants.
      SETTING: Acute hospital, rehabilitation, and outpatient units of a clinical
      research center. PATIENTS: Patients with unilateral stroke were studied a few or
      many weeks after the ictus. MAIN OUTCOME MEASURES: Comparison was made between
      contraction strengths induced by maximal tetanic electrical stimulation of the
      dysfunctional and contralateral unaffected muscles. Maximal voluntary strength of
      the foot dorsiflexion forces was also measured. RESULTS: Compared with the range
      of electrically evoked contractile force of tibialis anterior between the limbs
      of healthy participants, the directly elicited force in stroke-impaired tibialis
      anterior was not significantly impaired. CONCLUSIONS: Modes of exercise therapy
      focused primarily on direct strengthening of striated musculature, as in
      resistive exercise training, are strategically questionable. Whether other
      approaches may be more effective remains to be proved. The central disability of
      the upper motor neuron syndrome is failure of rapid coordinated adjustment of
      graded high-frequency motoneuron firing in purposeful complex synergies.

PMID- 12223034
TI  - Williams syndrome: neuronal size and neuronal-packing density in primary visual
      cortex.
AB  - BACKGROUND: Williams syndrome (WMS) is a rare, genetically based syndrome
      associated with a hemideletion in chromosome 7 (7q11.22-23) and characterized by
      a unique constellation of somatic, brain, and cognitive features. Individuals
      with WMS demonstrate an unusual and uneven neuropsychological profile showing
      cognitive and visual spatial deficits juxtaposed with relative language
      preservation and excellent facial recognition. OBJECTIVES: A neuroanatomical
      hypothesis for these behavioral findings suggests predominant involvement of the
      dorsal portions of the hemispheres relative to the ventral portions, including
      preferential involvement of peripheral visual field cortical representations over
      central representation. Predominant involvement of magnocellular visual pathways,
      as opposed to parvocellular pathways, is also suggested by this hypothesis.
      SUBJECTS: We examined primary visual cortical area 17 in the right and left
      hemispheres in 6 age- and sex-matched autopsy specimens from 3 WMS-affected
      brains (1 male and 2 females; mean [SD] age, 44 [14] years) and 3 control brains
      (1 male and 2 females; mean age, 43 [11] years). DESIGN: Neurons in layers II,
      III, IVA, IVB, IVCalpha, IVCbeta, V, and VI were measured using an optical
      dissector method to determine possible differences between WMS-affected and
      control brains in cell-packing density, neuronal size, and neuronal size
      distribution. RESULTS: We found abnormalities in peripheral visual cortex in WMS
      affected brains, but not in magnocellular subdivisions. There was a hemisphere by
      layer IV interaction and a layer IV left hemisphere and diagnosis interaction in
      cell-packing density. Williams syndrome-affected brains showed increased cell
      packing density in left sublayer IVCbeta and an excess of small neurons in left
      layers IVA, IVCalpha, IVCbeta, V, and VI. CONCLUSIONS: Cell measurements differ
      in peripheral visual cortical fields of WMS, with significantly smaller, more
      closely packed cells in some layers on the left side. These cell-packing density
      and neuronal size differences may be related to visuospatial deficits in this
      population.

PMID- 12223035
TI  - Manual approach during hand gesture imitation.
AB  - BACKGROUND: Patients' tendency to draw near or into the target when copying
      figures, a phenomenon termed closing-in, has been previously described. That the
      closing-in could occur when copying hand gestures has also been noted.
      OBJECTIVES: To study a patient with corticobasal degeneration to quantify his
      manual approach behavior and to test a possible working memory hypothesis.
      METHODS: The subject of this study is a patient with severe ideomotor apraxia
      from probable corticobasal degeneration. Fluorine 18-labeled deoxyglucose
      positron emission tomographic findings revealed a hypometabolism involving the
      bilateral parietotemporal and the right frontal lobes. When asked to copy an
      examiner's (J.C.K.) hand gesture, the patient approached, touched, or grasped the
      examiner's hand, a behavior mostly consistent with the closing-in behavior
      previously proposed. To investigate the frequency and severity of closing-in, the
      patient was asked to copy 20 meaningless hand gestures (10 simple and 10
      complex). Copying the 20 hand gestures was performed with either the left or the
      right hand while the patient was seated opposite the examiner (across condition)
      or on the same side of the examiner (lateral condition). RESULTS: Of the 80
      trials, closing-in occurred in 43 (53.8%) (35 with approaching, 6 with touching,
      and 2 with grasping). The closing-in was more frequent and more severe when
      gesturing with the left than the right hand, but it did not differ between the
      lateral and across conditions and between simple and complex gestures.
      CONCLUSIONS: Corticobasal degeneration might be associated with aberrant manual
      approach behavior. Although our results do not support the working memory
      hypothesis, frontal dysfunction might have led to a loss of voluntary control of
      ontologically primitive propensity to move the forelimb in the direction to which
      one attends.

PMID- 12223036
TI  - Mesial temporal lobe abnormalities in a family with 15q26qter trisomy.
AB  - BACKGROUND: The association of chromosomal imbalances and neurologic
      abnormalities is well known. OBJECTIVE: To describe a family with 2 brothers
      presenting with 15q trisomy due to a maternal equilibrated translocation
      involving chromosomes 12 and 15. DESIGN, SETTING, AND PATIENTS: Among patients
      with epilepsy followed up in our hospital, we identified 2 brothers with epilepsy
      and mental retardation who presented dysmorphic features. Detailed clinical,
      electroencephalographic, and magnetic resonance imaging investigation was
      performed. In addition, we collected blood samples for karyotyping. RESULTS:
      Clinical findings included minor dysmorphic features, mental retardation,
      abnormal behavior, and secondary generalized epilepsy. Electroencephalography
      showed left temporal slow waves in the older brother and background abnormality
      associated with generalized and multifocal epileptiform discharges in the other.
      Their magnetic resonance images showed mesial temporal lobe malformation,
      including the hippocampus and parahippocampal and fusiform gyri, with abnormal
      shape and axis. CONCLUSIONS: To our knowledge, this is the first report of mesial
      temporal lobe malformation associated with chromosomal abnormalities. Our finding
      may contribute to the understanding of the genetic mechanisms involved in central
      nervous system malformations, especially in the mesial temporal lobe structures.

PMID- 12223037
TI  - CADASIL mimicking primary angiitis of the central nervous system.
AB  - BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy (CADASIL) and primary angiitis of the central nervous
      system (PACNS) share several clinical and radiological features. However, digital
      subtraction angiogram (DSA) is generally reported as normal in CADASIL, whereas
      lumen irregularities in distal cerebral arteries indicate PACNS. OBJECTIVE: To
      describe a potential pitfall of DSA interpretation, which led to the tentative
      diagnosis of PACNS in a CADASIL patient. PATIENT AND METHODS: Single case
      observation. RESULTS: A 47-year-old man sustained recurrent subcortical infarcts.
      He had mild hypercholesterolemia and migraine. His family history was
      unremarkable. The underlying cause of stroke could not be elucidated.
      Transcranial Doppler sonography revealed decreased intracranial blood flow
      velocities compatible with CADASIL. Lumen irregularities of several peripheral
      intracranial arteries were seen on DSA, which suggested PACNS. CADASIL was
      confirmed by results from skin biopsy and genetic testing. CONCLUSIONS: First, in
      patients with CADASIL, DSA can show segmental lumen irregularities in distal
      cerebral arteries suggestive of PACNS. Second, the potential role of transcranial
      Doppler sonography to distinguish CADASIL from PACNS deserves further testing.

PMID- 12223038
TI  - Progressive stroke following soccer playing: successful treatment by emergency
      carotid endarterectomy.

PMID- 12223039
TI  - Vaccines to treat encephalitis lethargica: human experiments at the Neurological
      Institute of New York, 1929-1940.
AB  - BACKGROUND: Encephalitis lethargica, first observed in 1915, became a pandemic.
      Because of its presumed infectious basis, there were early attempts to treat it
      with vaccines. The history of the use of these vaccines has not been analyzed.
      OBJECTIVE: To document the use of vaccines to treat patients with encephalitis
      lethargica, and, more specifically, the 1000 patients whose treatments took place
      with the support of the William J. Matheson Commission at the Neurological
      Institute of New York, NY (1929-1940). MATERIALS AND METHODS: Archival materials
      were analyzed, including the files of the Matheson Commission and the medical
      records of patients evaluated at the Neurological Institute of New York. RESULTS:
      Two primary vaccines were used to combat encephalitis lethargica. The Rosenow
      vaccine was based on clinical and experimental evidence suggesting that the
      causative agent was Streptococcus viridans. The Levaditi C (later Gay F) vaccine
      was based on evidence that herpes simplex virus was the cause. During a
      therapeutic study conducted from 1929 through 1940, 1000 patients received
      treatment. Assessing therapeutic efficacy was problematic, but the Gay vaccine
      was considered more effective. CONCLUSIONS: Because of its presumed infectious
      basis, several vaccines were used to treat encephalitis lethargica, with the
      study at the Neurological Institute constituting the largest organized
      therapeutic attempt. Many of today's standard clinical trial methods were not
      practiced, which made it difficult to determine efficacy.

PMID- 12223040
TI  - Nonepileptic seizures: an honest approach to provocative testing is feasible.

PMID- 12223042
TI  - Weight gain, antipsychotic drug treatment and pharmacogenomics.

PMID- 12223043
TI  - Will pharmacogenomics alter the role of patents in drug development?

PMID- 12223045
TI  - SNPs and pharmacogenomics.

PMID- 12223046
TI  - Microarrays in pharmacogenomics--advances and future promise.
AB  - With their ability to provide global views of genome sequence and gene activity,
      microarrays have emerged as key analytical tools in the field of
      pharmacogenomics. Vast amounts of data must be collected and analyzed to meet
      pharmacogenomics' ambitious goals, ranging from identifying markers that predict
      individuals' responses to therapy to discovering new drug targets. Microarrays
      will be instrumental to these efforts because they provide bountiful sources of
      gene expression and genotypic data. Attesting to their productivity, microarrays
      have been the central technology used in thousands of peer-reviewed publications
      and have also become important contributors to many databases including PharmGKB,
      the Cancer Microarray Database and the database of single nucleotide
      polymorphisms (dbSNP). Microarrays are also making more focused contributions,
      however, in helping pursue hypothesis-driven inquiries that extend or complement
      broad genomic surveys. In addition, their potential as clinical tools is being
      increasingly recognized. This review identifies some of the varied and changing
      needs of pharmacogenomics research and discusses the ways in which microarrays
      are tending to these demands. The technique's strongpoints and limitations are
      examined, as well as its future potential.

PMID- 12223047
TI  - The emergence of resistance to targeted cancer therapeutics.
AB  - Drug resistance has always been a concern in cancer treatment, often blamed on
      the genetic complexity and instability of tumor cells. While studies of cancer
      cell lines have implicated an array of potential mechanisms, it has been
      difficult to translate these insights into clinically meaningful improvements in
      cancer treatment. The successful deployment of molecularly targeted therapeutics
      in some cancers has led to widespread optimism that this approach will become
      broadly applicable. Despite their early promise in the clinic, the novel
      therapeutics are often plagued with the age old problem of acquired drug
      resistance. Progress in understanding why certain patients respond and why some
      develop resistance can be made rapidly through studies of the drug target in
      tumor tissue from patient. One important lesson is that many cancers, even in the
      most advanced stages, continue to rely on a limited number of critical oncogenic
      signals for maintenance of the malignant phenotype. This article reviews the
      mechanisms of drug resistance to a variety of cancer therapeutics and provides an
      approach for how measures of drug target activity can be incorporated into
      clinical trial design.

PMID- 12223048
TI  - The impact of pharmacogenomics on gastrointestinal cancer therapy.
AB  - Recently, we have seen major advances in the chemotherapy of gastrointestinal
      tumors, in particular colorectal cancer, leading to a substantial increase in
      overall survival of the patients. However, clinical efficacy and also toxicity of
      a given chemotherapy are still largely unpredictable for the individual patient.
      Amongst other variables, genetic polymorphisms determine the interindividual
      heterogeneity in both toxicity and therapeutic efficacy. In this review we
      present current evidence on host genetic polymorphisms that affect the toxicity
      or efficacy of three drugs commonly used for the treatment of gastrointestinal
      malignancies, 5-fluorouracil, irinotecan and oxaliplatin.

PMID- 12223049
TI  - Functional genomics of osteoarthritis.
AB  - Functional genomics is a challenging new way to address a complex disease like
      osteoarthritis on a molecular level. Despite osteoarthritis being ultimately a
      biochemical problem, mainly characterized by an imbalanced cartilage matrix
      turnover, a deeper understanding of molecular events within the tissue cells
      (i.e., the chondrocytes) will provide not only a better understanding of
      pathogenetic mechanisms but also new diagnostic markers and cellular targets for
      therapeutic intervention. This innovative technology represents a challenging
      approach complementing (not replacing) classical research in previously described
      and new disease-relevant genes: large-scale functional genomics will open up new
      areas of so far unrecognized molecular networks. This will include as yet
      unidentified players in the anabolic-catabolic balance of matrix turnover of
      articular cartilage as well as disease-relevant intracellular signaling cascades
      so far hardly investigated in articular chondrocytes. However, care must be taken
      not to over or misinterpret results and some major challenges must be overcome in
      order to properly utilize the potential of this technology in the field of
      osteoarthritis.

PMID- 12223050
TI  - Information management systems for pharmacogenomics.
AB  - The value of high-throughput genomic research is dramatically enhanced by
      association with key patient data. These data are generally available but of
      disparate quality and not typically directly associated. A system that could
      bring these disparate data sources into a common resource connected with
      functional genomic data would be tremendously advantageous. However, the
      integration of clinical and accurate interpretation of the generated functional
      genomic data requires the development of information management systems capable
      of effectively capturing the data as well as tools to make that data accessible
      to the laboratory scientist or to the clinician. In this review these challenges
      and current information technology solutions associated with the management,
      storage and analysis of high-throughput data are highlighted. It is suggested
      that the development of a pharmacogenomic data management system which integrates
      public and proprietary databases, clinical datasets, and data mining tools
      embedded in a high-performance computing environment should include the following
      components: parallel processing systems, storage technologies, network
      technologies, databases and database management systems (DBMS), and application
      services.

PMID- 12223051
TI  - Genetically defined pancreatic beta cell failure.
AB  - The major subtypes of diabetes mellitus (DM) are complex diseases in which the
      interactions between genetic susceptibility and metabolic, immunologic and
      environmental factors ultimately lead to the clinical phenotype. The unraveling
      of these factors and the study of their contribution to the pathogenesis of DM is
      a process of unimaginable complexity. As a result, despite the individual
      differences in DM phenotype, most patients with DM receive treatment according to
      generalized treatment protocols, only discriminating between Type 1 and Type 2 DM
      and not related to the individual genetic background of the patients.
      Nevertheless, in recent years, much progress has been made in the search for
      genetic factors in DM. As an example, the recognition of monogenetic defects in
      beta cell function has lead to the definition of novel DM subtypes, which have
      important implications for the individual therapeutic approach for these patients
      and the understanding of the etiology of DM.

PMID- 12223052
TI  - The hunt for new genes and polymorphisms that can control the response to drugs.
AB  - There has been a great increase in the knowledge of understanding the genetic
      basis for individual variation in response to drugs. The study of variation in
      gene structure (polymorphism) can now predict the likely metabolic behavior in an
      individual for a number of drugs. This review documents the different strategies
      that can be used to find new genes and polymorphisms within these genes.
      Candidate genes can be used in case-control studies or studies where the parents
      of the person having an adverse effect from the drug are used as controls. New
      genes are being discovered in the drug development process and the technological
      development in molecular biology is expected to greatly enhance knowledge of the
      genes that regulate drug metabolism.

PMID- 12223053
TI  - Designing and implementing special-purpose databases: lessons from the
      pharmacogenetic network.
AB  - The Pharmacogenetics Research Network, which has the long-term goal of genotype
      phenotype correlation related to pharmacotherapy, mandates timely electronic
      publication of results by participating research groups through submission to
      PharmGKB, the consortium's repository database. Because informatics expertise
      across groups varies, many groups need help in managing their own data and in
      generating electronic submissions. To assist these operations, we perform a needs
      assessment to determine an optimum database implementation strategy, which varies
      from standalone microcomputer database application to Web-based solutions,
      depending on the group and problem scope. Solution implementation is coupled with
      transfer of expertise through hands-on training, so as to reduce the groups' long
      term dependence on us. Where multiple groups face common problems, such as
      managing genotyping data or clinical study support, we have devised generic
      software that can be reused in its entirety by individual groups, or customized
      with modest effort.

PMID- 12223054
TI  - Recent developments in laboratory automation using magnetic particles for genome
      analysis.
AB  - The majority of research for genome analysis has shifted from nucleic acid
      sequencing to the biological functional analysis of each gene. Based on past
      success, it may not be long before genome diagnostics becomes a widespread tool
      in human, veterinary and botany research fields. Genome analysis involves the
      processes of nucleic acid purification, amplification, labeling and signal
      detection (specific reaction, separation and signal counting). Except for the
      purification of nucleic acids, the other processes cannot be achieved without
      instruments, resulting in the advancement of automation processes. Since
      purification of nucleic acids can be done manually, automating this process has
      been delayed. However, because the purification of nucleic acids using magnetic
      particles is suitable for automation, its development has also been accelerated.
      The need for full automation for other processes is not as great because the
      majority of genome analysis is to identify the nucleic acid sequence and analyze
      genome expression. However, once useful diagnostic tools are generated, the
      desire for full automation will significantly increase. In order to develop
      realistic and practical automation, various technologies developed for each
      process in genome analysis have to be evaluated and only a few technologies,
      useful for automation, selected. The other key factor in automation is the
      development of methods to manage reagents and reaction mixtures precisely without
      any risks specifically related to genome handling, such as cross-contamination.
      Methods using magnetic particles, which have been used for the automation of
      nucleic acid purification and immunoassay, appear to be the most promising way to
      automate processes used in biological research.

PMID- 12223055
TI  - Affymetrix, Inc.
AB  - Affymetrix creates breakthrough tools for applications in the drug development
      process and pharmacogenomics. By applying the principles of semiconductor
      technology to the life sciences, Affymetrix has created the GeneChipmicroarray
      platform for both gene expression analysis (mRNA) and genetic analysis (DNA). The
      company's integrated system is setting the standard for basic research and target
      identification and is now being adopted in additional research applications, such
      as target validation and toxicogenomics, as well as in healthcare applications
      including clinical trials and health management. Affymetrix' current customers
      include pharmaceutical, biotechnology, agrochemical, diagnostic and consumer
      product companies as well as academic, government and other non-profit research
      institutions. Additional information on Affymetrix can be found at
      www.affymetrix.com.

PMID- 12223056
TI  - Variagenics, inc.
AB  - Variagenics, Inc. develops molecular diagnostic tests by identifying genetic
      markers associated with response to cancer therapies, with the goal of optimizing
      patient care. Toward this end, the company analyzes genetic variations in both
      normal and tumor cells, including SNPs, haplotypes, loss of heterozygosity, and
      gene expression levels. The company's approach of analyzing multiple types of
      genetic variations increases the likelihood of finding significant associations
      with drug response and successfully developing diagnostics. Variagenics is
      pursuing marker identification and diagnostic development through both
      biopharmaceutical collaborations and internal research programs.

PMID- 12223057
TI  - Promising therapeutic targets for antileishmanial drugs.
AB  - Current treatments for the parasitic disease leishmaniasis are unsatisfactory due
      to their route of administration, toxicity and expense. Resistance is also
      developing to first-line antimonial drugs. Fortunately, a handful of
      antileishmanial agents, such as the orally available compound miltefosine, are
      currently in clinical trials. In addition, several promising drug targets and
      lead molecules are being studied with the goal of developing new antileishmanial
      agents. Drug candidates have been identified through the continued investigation
      of parasite sterol metabolism and parasite proteases. New antileishmanial
      molecules have also been discovered through the study of novel targets and
      pathways, such as the bisphosphonate inhibitors of isoprenoid biosynthesis. This
      review presents a synopsis of the drug targets and lead compounds that have been
      investigated over the last few years against leishmaniasis, gives a perspective
      on the chemotherapeutic potential of each and discusses some of the obstacles to
      antileishmanial drug development.

PMID- 12223058
TI  - The role of DC-SIGN and DC-SIGNR in HIV and Ebola virus infection: can potential
      therapeutics block virus transmission and dissemination?
AB  - Sexual transmission of HIV requires that the virus crosses mucosal barriers and
      disseminates into lymphoid tissue, the major site of viral replication. To
      achieve this, HIV might engage DC-SIGN, a calcium dependent lectin that is
      expressed on mucosal dendritic cells (DCs), which binds avidly to HIV. DC-SIGN
      and other attachment factors are likely to account for the well-known ability of
      DCs to enhance infection of T cells by HIV. Attachment of HIV to DC-SIGN might
      thus enhance viral spread in mucosal tissues and, by taking advantage of the
      inherent capacity of DCs to migrate into lymphoid tissue, might promote viral
      dissemination within the host. DC-SIGN and a related molecule, termed DC-SIGNR,
      also enhance infection by Ebola virus. The expression of these lectins on early
      targets of Ebola virus infection, like liver endothelial cells and alveolar
      macrophages, suggests an important role for DC-SIGN and DC-SIGNR in the
      establishment of Ebola infection. This article reviews the interaction of DC-SIGN
      and DC-SIGNR with HIV and Ebola, discusses the mechanism of DC-SIGN-mediated
      viral transmission and examines how this process could be inhibited by potential
      therapeutics.

PMID- 12223059
TI  - HIV-1 integrase and RNase H activities as therapeutic targets.
AB  - The retroviruses are a large, diverse family of enveloped RNA viruses defined by
      their structure, composition and replicative properties. The hallmark of the
      family is its replicative strategy, essential steps of which include reverse
      transcription of the viral RNA and the subsequent integration of this DNA into
      the genome of the cell. These steps are performed by two viral-encoded enzymes,
      reverse transcriptase (RT), which possesses DNA polymerase and ribonuclease H
      (RNase H) activities, and integrase (IN). These enzymes are excellent targets for
      retroviral therapy since they are essential for viral replication. Numerous
      substances capable of inhibiting the DNA polymerase activity of HIV-1 RT are
      available, while few specific inhibitors of RNase H activity have been described.
      IN is absolutely necessary for stable and productive infection of cells. Some IN
      inhibitors have been recently reported and are available demonstrating the
      potential of IN as an antiviral target. This paper is an overview of the
      inhibitors of RNase H and IN and describes the most promising inhibitors.

PMID- 12223060
TI  - Airway smooth muscle: new targets for asthma pharmacotherapy.
AB  - Asthma, a chronic disease increasing in prevalence worldwide, is characterised by
      reversible airway obstruction, airway inflammation and airway smooth muscle (ASM)
      cell hyperplasia. The traditional view of ASM in asthma, as a regulator of
      bronchomotor tone, is rapidly changing. New evidence suggests that ASM cells also
      play an important role in the perpetuation of airway inflammation and airway
      remodelling. This review discusses the synthetic function of ASM cells, defined
      as the ability to secrete cytokines, chemokines and growth factors and express
      surface receptors that are important for cell adhesion and leukocyte activation.
      Finally, the efficacy of established asthma therapies in modifying the synthetic
      function of ASM cells are compared and novel targets for pharmacological
      intervention are discussed.

PMID- 12223061
TI  - Fibroblast growth factors in cancer: therapeutic possibilities.
AB  - The fibroblast growth factor (FGF) family of signalling molecules and its
      receptors (FGFRs) contribute to normal developmental and physiological processes.
      However, the subversion of this powerful growth stimulatory pathway has been
      implicated in the generation of a variety of pathological conditions. This review
      focuses on the role of FGF/FGFRs in cancer. The case will be made that this
      signalling pathway is associated with and functionally important for the growth
      of some human tumours. As such, FGF/FGFRs can be viewed as rational therapeutic
      oncology targets and strategies used to inhibit these molecules are discussed.
      The therapeutic exploitation of tumour-associated FGFR expression to deliver
      toxins or antiproliferative signals to tumour cells is also reviewed, as is the
      use of FGFs as protein therapeutics to alleviate the side effects of cancer
      therapy.

PMID- 12223062
TI  - COX-2 - a target for preventing hepatic carcinoma?
AB  - Hepatocellular carcinoma (HCC) is one of the most common reasons for malignancy
      related death in Africa and Asia and is still recognised as the leading cancer in
      men in Taiwan. Despite enthusiastic efforts in early diagnosis, aggressive
      surgical treatment and application of additional nonoperative modalities, its
      prognosis is still dismal. This emphasises the necessity to develop new measures
      and strategies for its prevention. Inducible cyclooxygenease 2 (COX-2) is an
      immediate-early (IE) response gene and extensive studies conducted over the past
      few years have recognised its overexpression in several carcinomas and thus its
      implication in carcinogenesis. Recent studies have suggested that overexpression
      of COX-2 might be one of the leading factors in hepatic carcinogenesis. COX-2 can
      induce angiogenesis via vascular endothelial growth factor (VEGF) and
      prostaglandin production and can also inhibit apoptosis by inducing the
      antiapoptotic factor Bcl-2 as well as activating antiapoptotic signalling through
      Akt/PKB. Therefore, the use of selective inhibitors for the downregulation of COX
      2 activity might be a target for preventing hepatic carcinoma development.

PMID- 12223063
TI  - Proteomic analysis of transcription factor interactions in myeloid stem cell
      development and leukaemia.
AB  - Recent results indicate that interactions of transcription factors with other
      nuclear proteins play an important role in stem cell development, lineage
      commitment and differentiation in the haematopoietic system, and the pathogenesis
      of myeloid leukaemias. High-throughput proteomics by mass spectrometric analysis
      of gel-separated proteins can identify multi-protein complexes and changes in the
      expression of multiple proteins simultaneously. This review describes an
      application of proteomic methods (2D gel electrophoresis (GE) and mass
      spectrometry (MS)), which can be used to identify regulated protein targets of
      transcription factors important in myeloid differentiation and leukaemia. This
      global high-throughput functional proteomics approach could lead to new insights
      into the network of protein-protein interactions and target proteins involved in
      myeloid stem cell development and leukaemia as well as provide new targets for
      rational pathogenesis-based therapies of leukaemia and cancer.

PMID- 12223064
TI  - Death-associated protein kinase as a potential therapeutic target.
AB  - Death associated protein kinase (DAPK) is a calmodulin (CaM)-regulated
      serine/threonine protein kinase implicated in diverse apoptosis pathways,
      including those involved in neuronal cell death and tumour suppression. The
      requirement of DAPK catalytic activity for its proposed cell functions and the
      validation of protein kinases as therapeutic targets demand that DAPK be examined
      as a potential therapeutic target in human disease. The relevant placement of
      DAPK activity in apoptosis pathways is at an early stage of investigation, making
      its study as a therapeutic target tenuous. However, the current body of knowledge
      raises the possibility of DAPK as a therapeutic target for diseases characterised
      by rapid neurodegeneration, such as stroke or traumatic brain injury. The unmet
      need in these diseases is for an acute treatment schedule that might reduce
      neuronal loss. Bioavailable inhibitors of DAPK catalytic activity that target the
      central nervous system have a potential to fill this need. The development of
      such DAPK inhibitors is now feasible based on the recent emergence of enabling
      technology and knowledge. These include a quantitative and selective enzyme
      assay, a high resolution structure of the active catalytic domain and discovery
      of cell-permeable, low molecular weight inhibitors of CaM kinases that cross the
      blood-brain barrier. DAPK as a potential therapeutic target for cancer is less
      attractive due to the incomplete state of knowledge about DAPK and inherent
      limitations in drug development for the discovery of specific activators of genes
      downregulated by promoter hypermethylation. This article provides a brief summary
      of relevant research and the rationale that is at the foundation of this opinion.

PMID- 12223065
TI  - Peptide ligands in antibacterial drug discovery: use as inhibitors in target
      validation and target-based screening.
AB  - There is an urgent need to develop novel classes of antibiotics to counter the
      inexorable rise of resistant bacterial pathogens. Modern antibacterial drug
      discovery is focused on the identification and validation of novel protein
      targets that may have a suitable therapeutic index. In combination with assays
      for function, the advent of microbial genomics has been invaluable in identifying
      novel antibacterial drug targets. The major challenge in this field is the
      implementation of methods that validate protein targets leading to the discovery
      of new chemical entities. Ligand-directed drug discovery has the distinct
      advantage of having a concurrent analysis of both the importance of a target in
      the disease process and its amenability to functional modulation by small
      molecules. VITA is a process that enables a target-based paradigm by using
      peptide ligands for direct in vitro and in vivo validation of antibacterial
      targets and the implementation of high-throughput assays to identify novel
      inhibitory molecules. This process can establish sufficient levels of confidence
      indicating that the target is relevant to the disease process and inhibition of
      the target will lead to effective disease treatment.

PMID- 12223066
TI  - Target validation and drug discovery using genomic and protein-protein
      interaction technologies.
AB  - After the successful completion of the human genome project, mapping of the human
      proteome has become the next important challenge facing the biotech and
      pharmaceutical industries. Identification of the 'right' target(s) is now a
      critical part of the process because of the cost of drug discovery. Compounding
      this situation is the fact that the pharmaceutical industry faces a further
      challenge of being able to sustain current and historical growth rates. Hence,
      the discovery of new drug targets is important for developing new drug leads that
      can become preclinical drug candidates. Proteomics is the next phase of the
      effort whereby the human genome can be understood. However, mapping the human
      proteome presents a daunting challenge. Proteomics involves several essential
      components with the most significant being the discovery and description of all
      protein-protein interactions. Once this compendium is available, a secondary and
      equally important initiative will be to decipher proteins that are differentially
      expressed in any given disease condition. At this point, the critical focus will
      be to select the most relevant proteins, understand their partner interactions
      and then further winnow them to the point where they are relevant pharmaceutical
      target candidates. This paradigm can be compared to finding the relevant 'needle
      in the proteome haystack'. This review describes the use of genomic and protein
      protein interaction technologies to identify and validate these 'needles' as the
      first step in the drug discovery process.

PMID- 12223067
TI  - A diversity of therapeutic targets.

PMID- 12223068
TI  - Quorum sensing: an emerging target for antibacterial chemotherapy?
AB  - The emergence of bacterial strains exhibiting resistance to multiple antibiotic
      classes poses a major threat to medicine and public health. This has been
      compounded over the last few decades by the failure of drug discovery programmes
      to provide new broad spectrum antibacterials with novel modes of action. As a
      consequence, there is renewed interest in antibacterial targets which disrupt the
      capacity of pathogenic bacteria to cause infection by attenuating virulence. In
      this respect, one crucial feature of almost all bacterial infections is that the
      pathogen must attain a critical cell population density sufficient to overwhelm
      the host defences. Many pathogens are now known to regulate diverse physiological
      processes, including virulence, in a cell density dependent manner through cell
      cell communication. This phenomenon, which relies upon the interaction of a
      diffusible signal molecule with a sensor kinase or response regulator, has become
      known as 'quorum sensing'. This review considers the molecular basis of quorum
      sensing and whether it constitutes a potential therapeutic target for the design
      of small molecule antagonists capable of controlling infection by attenuating
      adaptation to the host environment.

PMID- 12223070
TI  - Targeting the myocardial sodium-hydrogen exchange for treatment of heart failure.
AB  - Although the past number of years have seen a substantial improvement in the
      therapeutic approaches for the treatment of heart failure, mortality rates
      continue to be high. Moreover, the incidence of heart failure is expanding
      rapidly. Sodium-hydrogen exchange (NHE) is a key target for the treatment of
      heart failure. NHE is a major mechanism for intracellular pH regulation in most
      cell types, including the cardiac cell. Seven isoforms of NHE have been
      identified so far although cardiac cells possess primarily the ubiquitous NHE-1
      subtype. NHE-1 is a major contributor to ischaemic and reperfusion injury and NHE
      1 inhibitors exert marked cardioprotective effects, particularly when
      administered before ischaemia, findings which have now been extended to clinical
      trials. It is emerging that NHE-1 also contributes to chronic maladaptive
      myocardial responses to injury (myocardial remodelling) and may contribute to the
      development of heart failure. Experimental studies using both in vitro approaches
      as well as animal models of heart failure have consistently demonstrated a
      beneficial effect of NHE-1 inhibitors in terms of inhibition of hypertrophy in
      response to various stimuli as well as inhibiting heart failure after coronary
      artery ligation. These effects occurred independently of any infarct size
      reducing effects of NHE-1 inhibitors or on any direct effects on afterload thus
      indicating a direct effect on the myocardial remodelling process. In fact, it
      appears that NHE-1 may represent a common downstream mediator for various
      hypertropic factors such as angiotensin II, endothelin-1 and beta(1) adrenergic
      receptor activation. NHE-1 inhibition, therefore, represents a potentially
      effective new therapeutic approach for the treatment of heart failure.

PMID- 12223071
TI  - Lipoprotein-associated phospholipase A2: a target directed at the atherosclerotic
      plaque.
AB  - Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is so named because it is
      found in human plasma largely associated with low-density lipoprotein (LDL). It
      is secreted by macrophages and able to hydrolyse oxidised fatty acids from
      oxidised phospholipids in LDL thereby releasing pro-atherogenic
      lysophosphatidylcholine and fatty acids. Inhibition of this enzyme activity was
      proposed to be antiatherogenic and this hypothesis has been confirmed both in
      vitro and in animal studies using specific inhibitors. In addition, the enzyme
      has been shown to be present in human atherosclerotic plaques and to be a
      potential risk factor for coronary heart disease in epidemiological studies.
      However, Lp-PLA(2) is identical to platelet-activating factor acetylhydrolase
      (PAF-AH), whose activity is regarded as antiatherogenic. The role of this enzyme
      in humans, represented as Lp-PLA(2) or PAF-AH, remains to be clarified. Specific
      and potent inhibitors of Lp-PLA(2) have been described and help address this
      question. This is a novel approach directed specifically towards processes in
      atherogenesis which take place in the artery wall. Innovative strategies for
      clinical development are required to progress novel molecular strategies such as
      this.

PMID- 12223069
TI  - Targeting T cell costimulation in autoimmune disease.
AB  - Many factors contribute to the pathogenesis of autoimmune diseases. Targets for
      treating such debilitating diseases will become more apparent by understanding
      the nature of immune activation. This review examines the possibility of
      targeting costimulation and discusses the molecules found on the T cell and the
      antigen-presenting cell (APC) that participate in T cell activation. Although new
      molecules continue to be discovered, the functions of B7-1 (CD80), B7-2 (CD86),
      CD28, cytotoxic T lymphocyte antigen 4 (CTLA-4), inducible costimulator (ICOS),
      programmed death 1 (PD-1), OX 40 (CD134) and CD40 ligand (CD40L, CD154) are now
      sufficiently understood that immunologists are targeting them to manipulate T
      cells to slow the progression of autoimmune diseases or treat tumours through the
      increase in T cell activation. CD28, ICOS, OX 40 and CD40L are considered the
      costimulatory molecules that increase T cell activation. However, ICOS and OX 40
      appear to act on memory cells while CD28 is predominantly a naive T cell
      activator. Most therapies in the treatment of autoimmunity that target these
      molecules work through blockade of their function with receptor specific
      immunoglobulin (Ig). CTLA-4 and PD-1 are considered to be the inhibitory T cell
      costimulators. While stimulating CTLA-4 has not been a widely used therapy, using
      soluble CTLA-4Ig to block B7 and disrupt the B7/CD28 pathway is fairly common.
      The majority of therapeutic use for PD-1 stems from targeting PD-1 with its
      natural ligand. It is hoped that therapies targeting costimulation may provide a
      means of conserving the patient's normal T cell repertoire and immune function
      whilst eliminating or suppressing autoreactive T cells and thus provide a more
      efficient means to treat autoimmune disease.

PMID- 12223072
TI  - Peripheral metabotropic glutamate receptors as drug targets for pain relief.
AB  - The relatively new family of G-protein-coupled metabotropic glutamate receptors
      (mGluRs) is comprised of eight cloned subtypes, which are classified into three
      groups based on their sequence homology, signal transduction mechanisms and
      receptor pharmacology. It is now well-established that mGluRs in the central
      nervous system are essential for neuroplasticity associated with normal brain
      functions but are also critically involved in various neurological and
      psychiatric disorders. Recent anatomical and behavioural evidence suggests an
      important role of mGluRs in peripheral tissues in animal models of inflammatory
      and neuropathic pain. Once the cellular effects of peripheral mGluR activation
      and inhibition are better understood, certain peripheral mGluR subtypes may
      become important novel therapeutic targets for the relief of pain associated with
      peripheral tissue injury. Peripherally acting drugs that modulate nociceptive
      processing through mGluRs should have the advantage of lacking the central side
      effects commonly observed with drugs interfering with glutamatergic transmission
      in the central nervous system.

PMID- 12223073
TI  - Functional genomics in neuropsychiatric disorders and in neuropharmacology.
AB  - The rapidly accumulating amount of information concerning gene and protein
      expression patterns produced by functional genomics, proteomics and
      bioinformatics is presently providing new targets for drug development.
      Furthermore, the analysis of gene expression in cells and tissues affected by a
      disease may reveal the underlying metabolic pathways and cellular processes
      affected. Finally, changes in gene expression may be used in either diagnostics
      or the monitoring of drug responses. This review focuses on advances in the use
      of functional genomics in neurological and neuropsychiatric diseases and
      neuropsychopharmacology. Although the number of published studies in this field
      is still limited, it already appears that this strategy may become a fruitful
      means in the analysis of the aetiology of neuropsychiatric disorders and the
      search for novel neuropharmacological drugs.

PMID- 12223074
TI  - Gene targets of antisense therapies in breast cancer.
AB  - Advances in molecular and cell biology have led to further understanding of the
      mechanisms of malignant growth and metastasis in human breast cancer cells.
      Initiation and progression of breast cancer results from mutations and the
      abnormal expression of many genes that control cellular proliferation,
      differentiation, invasion, metastasis and sensitivity to therapy (chemotherapy
      and radiation therapy). Inhibition of host immunity also plays a role in breast
      cancer progression. Many genes have been selected as targets for antisense
      therapy, including HER-2/neu, PKA, TGF-alpha, EGFR, TGF-beta, IGFIR, P12, MDM2,
      BRCA, Bcl-2, ER, VEGF, MDR, ferritin, transferrin receptor, IRE, C-fos, HSP27, C
      myc, C-raf and metallothionein genes. The strategy behind antisense therapy is
      the development of specific therapeutic agents that aim to correct the mutations
      and abnormal expression of cellular genes in breast tumour cells by decreasing
      gene expression, inducing degradation of target mRNA and causing premature
      termination of transcription. Many in vitro and in vivo studies have investigated
      the therapeutic efficacy of oligonucleotides and antisense RNAs. These studies
      have demonstrated specific inhibition of tumour cell growth by antisense therapy
      and have shown synergistic inhibitory effects between antisense oligonucleotides
      or antisense RNA and conventional chemotherapeutic drugs used in the treatment of
      breast cancer. Antisense oligonucleotides have been modified to improve their
      ability to penetrate cells, bind to gene sequences and downregulate target gene
      function. Many delivery systems for antisense RNA and antisense oligonucleotides
      have been developed, including virus vectors (retrovirus, adenovirus and adeno
      associate virus) and liposomes, to carry the antisense RNA or oligonucleotides
      through the cell membrane into the cytoplasm and nucleus of the tumour cells.
      However, in order to determine their feasibility antisense therapies need to be
      further investigated to determine their antitumour activity, pharmacokinetics and
      toxicity in breast cancer patients.

PMID- 12223075
TI  - Using Drosophila melanogaster to uncover human disease gene function and
      potential drug target proteins.
AB  - The fruit fly Drosophila melanogaster is a powerful genetic model organism, which
      has been instrumental in the determination of essential developmental and
      neurological pathways conserved from invertebrates to humans. With the completion
      of both the human and Drosophila genomes, the revelation that we are more similar
      to this simple organism than previously suspected was realised. 75% of human
      genetic disease genes have clear homologues in the fly. By utilising an array of
      genetic tools available to disrupt or misexpress these proteins, it is now
      feasible to perform large-scale genetic screens in Drosophila to identify other
      members of a particular human genetic pathway. This review outlines some of the
      reasons Drosophila is a useful tool for the discovery of therapeutic targets,
      covers some of the tools available to manipulate this organism and discusses
      specific examples of how to use Drosophila as a genetic test tube for revealing
      proteins which act in a common pathway.

PMID- 12223076
TI  - Potential of fumarate reductase as a novel therapeutic target in Helicobacter
      pylori infection.
AB  - Approximately 50% of the world's population carries Helicobacter pylori, a
      gastric bacterial pathogen linked to diseases including gastritis, ulcers and
      gastric cancer. Chemotherapies are being routinely used to treat systemic H.
      pylori infection. The common regimens consist of proton pump inhibitors (PPIs) or
      ranitidine bismuth citrate (RBC) and two antibiotics. Although these regimens
      efficiently eradicate H. pylori, the emergence of antibiotic-resistant H. pylori
      strains, their severe side effects and high costs are major drawbacks of these
      treatments. More efficient, economic and friendly drugs need to be developed.
      Fumarate reductase (FRD) catalyses the reduction of fumarate to succinate in the
      Krebs cycle and is also a key enzyme in anaerobic respiration with fumarate as
      the terminal electron acceptor for many facultative bacteria. H. pylori FRD
      contains three subunits, FrdA, FrdB and FrdC. Genome analysis and experimental
      evidence indicate that this enzyme appears to play an important role in the
      energy metabolism of H. pylori. In addition, FRD is essential for the
      colonisation of H. pylori in the acidic stomach as demonstrated in the mouse
      model of infection. Furthermore, three FRD inhibitors used to cure helminthic
      infection in animals and humans have both inhibitory and bactericidal effects on
      H. pylori. These lines of evidence indicate that FRD may be a promising
      chemotherapeutic target. Given that FrdA is strongly immunogenic in the sera from
      H. pylori-positive patients, this protein may also be used as a candidate for the
      development of an anti-H. pylori vaccine.

PMID- 12223077
TI  - Endotoxin antagonism: conceptual basis and therapeutic potential.
AB  - Since antiquity, physicians have beheld infections with deep consternation,
      knowing that a local lesion can have horrific systemic effects. Even in modern
      times, these effects have generally been impossible to control. Until recently,
      their ultimate cause was not well understood. Now, within the space of only a few
      years, the proximal cause of sepsis has been identified. Paralogous members of
      the Toll-like receptor (TLR) family sense infection and ignite the systemic
      inflammatory reaction that is known as sepsis. The question at hand has become a
      practical one: can this understanding be exploited to a therapeutic advantage?

PMID- 12223078
TI  - Tissue factor - a therapeutic target for thrombotic disorders.
AB  - Exposure of blood to tissue factor (TF) sets off the coagulation cascade. TF is a
      transmembrane protein that serves as an essential cofactor for activated
      coagulation factor VII (FVIIa). TF may be exposed locally by vascular injury
      (such as balloon angioplasty) or by spontaneous rupture of an atherosclerotic
      plaque. Expression of TF may also be induced on monocytes and endothelial cells
      in conditions like sepsis and cancer, causing a more generalised activation of
      clotting. TF may thus play a central role in thrombosis in a number of settings,
      and attention has turned to blocking TF as a means to prevent thrombosis.
      Inhibiting the inducible expression of TF by monocytes can be achieved by
      'deactivating' cytokines, such as interleukin (IL)-4, -10 and -13, or by certain
      prostanoids; by drugs that modify signal transduction, such as pentoxifylline,
      retinoic acid or vitamin D(3), or by antisense oligonucleotides. Such approaches
      are for the most part at a preclinical stage. The function of TF can be blocked
      by antibodies that prevent the binding of FVIIa to TF; by active site-inhibited
      FVIIa, which competes with native FVIIa for binding; by antibodies or small
      molecules that block the function of the TF/FVIIa complex; and by molecules, such
      as TF pathway inhibitor or nematode anticoagulant peptide C2, which inhibit the
      active site of FVIIa in the TF/FVIIa complex after first binding to activated
      factor X. The latter two agents have entered Phase II clinical trials. Perhaps
      most intriguing is the use of anti-TF agents locally, which holds the promise of
      stopping thrombosis at a specific site of injury without the bleeding risk
      associated with systemic anticoagulation.

PMID- 12223079
TI  - Biochemical aspects in autism spectrum disorders: updating the opioid-excess
      theory and presenting new opportunities for biomedical intervention.
AB  - Autism is a lifelong condition usually described as affecting social, cognitive
      and imaginative abilities. For many years, parents and some professionals have
      observed that in concordance with the behavioural and psychological symptoms of
      the condition, there are a number of physiological and biochemical correlates
      which may also be of relevance to the syndrome. One area of interest that
      encompasses many of these observations is the opioid-excess theory of autism. The
      main premise of this theory is that autism is the result of a metabolic disorder.
      Peptides with opioid activity derived from dietary sources, in particular foods
      that contain gluten and casein, pass through an abnormally permeable intestinal
      membrane and enter the central nervous system (CNS) to exert an effect on
      neurotransmission, as well as producing other physiologically-based symptoms.
      Numerous parents and professionals worldwide have found that removal of these
      exogenously derived compounds through exclusion diets can produce some
      amelioration in autistic and related behaviours. There is a surprisingly long
      history of research accompanying these ideas. The aim of this paper is to review
      the accompanying evidence in support of this theory and present new directions of
      intervention as a result of it.

PMID- 12223080
TI  - Novel G-protein-coupled receptor genes expressed in the brain: continued
      discovery of important therapeutic targets.
AB  - The rhodopsin family of G-protein-coupled receptors (GPCRs) is the largest known
      group of cell-surface mediators of signal transduction. The vast majority of
      these receptors were discovered by methods based upon shared sequence homologies
      found throughout this family. While such efforts identified a multitude of
      receptor subtypes for previously known ligands, numerous receptors have been
      discovered for which endogenous ligands were unknown. These receptors are
      commonly referred to as orphan receptors. One of the most important tasks of
      modern pharmacology lies in elucidating the functions of these receptors. Of
      particular interest are receptors with recognised expression in the central
      nervous system, given that many psychiatric and neurodegenerative disorders are
      mediated by unknown mechanisms. Hence, this collection of putative
      neurotransmitter and neuromodulator signal mediators represents a substantial and
      untapped resource for novel drug discovery. Recently, various methodologies have
      accelerated the discovery of novel ligands for these orphan receptors,
      identifying the basic components required for further physiological
      ligand/receptor system characterisation. Equipped with proven ligand
      identification strategies, the characterisation of all orphan GPCRs and the
      exploitation of their exciting potential as targets for the discovery of novel
      drugs is anticipated.

PMID- 12223081
TI  - Identification of new therapeutic targets for prevention of CNS inflammation.
AB  - Multiple sclerosis (MS) is a disease of complex pathologies, which involves
      infiltration by CD4(+) and CD8(+) T cells of and response within the central
      nervous system. Expression in the CNS of cytokines, reactive nitrogen species and
      costimulator molecules have all been described in MS. Notably, the cytokines IFN
      gamma and TNF are strongly expressed. Microglial cells in the CNS express
      costimulator molecules and it is assumed that they play a role in directing or
      inducing the T cell response. Transgenic experiments have tested the effects of
      overexpression of these molecules in mice and have shown that TNF has multiple
      effects in the CNS. These range from pro-inflammatory effects of soluble TNF
      signalling through one of its receptors TNF-RI, to protective/regenerative
      effects of membrane-associated TNF signalling through the other receptor, TNF
      RII. Although IFN-gamma induces nitric oxide production via the enzyme inducible
      nitric oxide synthase, which is immunosuppressive, IFN-gamma is predominantly pro
      inflammatory. In CNS disease in mice that involves CD8(+) T cells, IFN-gamma
      blockade is protective. Finally, microglial expression of the costimulator ligand
      B7.2 induces demyelinating pathology. Animal experiments therefore point to IFN
      gamma and costimulatory microglia as logical targets of therapy for MS. IFN-gamma
      represents a more accessible target and should therefore be pursued at the
      earliest opportunity.

PMID- 12223082
TI  - Mechanisms of tumour invasion and metastasis: emerging targets for therapy.
AB  - The progression of a tumour from one of benign and delimited growth to one that
      is invasive and metastatic is the major cause of poor clinical outcome in cancer
      patients. The invasion and metastasis of tumours is a highly complex and
      multistep process that requires a tumour cell to modulate its ability to adhere,
      degrade the surrounding extracellular matrix, migrate, proliferate at a secondary
      site and stimulate angiogenesis. Knowledge of the process has greatly increased
      and this has resulted in the identification of a number of molecules that are
      fundamental to the process. The involvement of these molecules has been shown to
      relate not only to the survival and proliferation of the tumour cell but, also to
      the processes of tumour cell adhesion, migration, and the tumour cells ability to
      degrade and escape the primary site as well as play a role in angiogenesis. These
      molecules may provide important therapeutic targets that represent the ability to
      target specific steps in the process of invasion and metastasis and provide
      additional therapies. The review focuses on representative key targets in each of
      these processes and summarises the state of play in each case.

PMID- 12223083
TI  - Hammerhead ribozymes for target validation.
AB  - Expensive failures in the pharmaceutical industry might be avoided by target
      validation at an early stage. Often, the full consequences of inhibiting a chosen
      drug target do not emerge until late in the development process. One option is to
      use hammerhead ribozymes as highly specific ribonucleases targeted exclusively at
      the mRNA encoding the target protein. The first part of this review is concerned
      with the mechanism and design of hammerhead ribozymes. This includes the
      chemistry of their action, specificity of cleavage and ability to discriminate
      between different mRNAs and selection of suitable cleavage sites. In considering
      their use for target validation, hammerhead ribozymes are divided into two
      categories. Endogenous ribozymes are transcribed inside the cell where they act
      whilst exogenous are introduced into the cell from outside. Exogenous ribozymes
      are synthesised chemically and must be protected against cellular nucleases.
      Information is provided on transfection methods and vectors that have been used
      with endogenous ribozymes as well as synthesis and chemical modification of
      exogenous ribozymes. Of proteins inhibited in cells or whole organisms, those in
      animal experiments are emphasised. Comparisons are made with other approaches,
      especially the use of antisense oligonucleotides or RNA.

PMID- 12223084
TI  - Three-dimensional domain swapping in homooligomeric proteins and its functional
      significance.
AB  - In the process of oligomeric structure formation through a mechanism of three
      dimensional domain swapping, one domain of a monomeric protein is replaced by the
      same domain from an identical monomer. The swapped "domain" can represent an
      entire tertiary globular domain or an element of secondary protein structure,
      such as an alpha-helix or a beta-strand. Different examples of three-dimensional
      domain swapping are reviewed; the functional importance of this phenomenon and
      its role in the development of new properties by some proteins in the process of
      evolution are considered. The contribution of three-dimensional domain swapping
      to the formation of linear protein polymers and amyloids is discussed.

PMID- 12223085
TI  - The structure and mechanism of action of cellulolytic enzymes.
AB  - The modern structural classification of polysaccharases comprising cellulase
      hemicellulase enzyme systems is discussed. Their catalytic domains are currently
      grouped into 15 of more than 80 known glycosyl hydrolase families, whereas
      substrate binding domains fall into 13 families. The structures of catalytic and
      substrate binding domains, as well as linker sequences, are briefly considered. A
      hypothetical mechanism of concerted action of catalytic and substrate binding
      domains of cellobiohydrolases on the surface of highly ordered cellulose is
      suggested.

PMID- 12223086
TI  - Dependence of prePhoA-phospholipid interaction in vivo and in vitro on charge of
      signal peptide N-terminus and content of anionic phospholipids in membranes.
AB  - Replacement of the positively charged signal peptide with neutral or negatively
      charged peptides due to substitution of Lys(-20) in the N-terminal region of the
      signal peptide leads to decreases in the rate of prePhoA membrane translocation
      in vivo and in the efficiency of prePhoA insertion into liposomes in vitro. The
      effect of anionic phospholipids on prePhoA insertion into model membranes is
      determined by the signal peptide N-terminus charge, while the dependence of
      prePhoA translocation across the cytoplasmic membrane in vivo is not, under the
      studied variations in the content of anionic phospholipids. This is evidence of
      the possibility of direct electrostatic interaction between the signal peptide N
      terminus and anionic phospholipids, which in vivo, however, seems to involve some
      proteins of the Sec machinery.

PMID- 12223087
TI  - Peroxyl radical is produced upon the interaction of hypochlorite with tert-butyl
      hydroperoxide.
AB  - As we reported previously, hypochlorite interacting with organic hydroperoxides
      causes their decomposition ((1995) Biochemistry (Moscow), 60, 1079-1086). This
      interaction was supposed to be a free-radical process and serve as a source of
      free radicals initiating lipid peroxidation (LP). The present study is the first
      attempt to detect and identify free radicals produced in the reaction of
      hypochlorite with tert-butyl hydroperoxide, (CH3)3COOH, which we have used as an
      example of organic hydroperoxides. We have used a direct method for free radical
      detection, EPR of spin trapping, and the following spin traps: N-tert-butyl-alpha
      phenylnitrone (PBN) and alpha-(4-pyridyl-1-oxyl)-N-tert-butylnitrone (4-POBN).
      When hypochlorite was added to (CH3)3COOH in the presence of a spin trap, an EPR
      spectrum appeared representing a superposition of two signals. One of them
      belonged to a spin adduct formed as a result of direct interaction of
      hypochlorite with the spin trap (hyperfine splitting constants were: abetaH =
      0.148 mT; aN = 1.537 mT; and deltaHPP = 0.042 mT for 4-POBN and abetaH = 0.190
      mT; aN = 1.558 mT; and deltaHPP = 0.074 mT for PBN). The other signal was
      produced by hypochlorite interactions with (CH3)3COOH itself (hyperfine splitting
      constants were: abetaH = 0.233 mT; aN = 1.484 mT; deltaHPP = 0.063 mT and abetaH
      = 0.360 mT; aN = 1.547 mT; deltaHPP = 0.063 mT for 4-POBN and PBN, respectively).
      Comparison of spectral characteristics of this spin adduct with those of tert
      butoxyl or tert-butyl peroxyl radicals produced in known reactions of (CH3)3COOH
      with Fe2+ and Ce4+, respectively, showed that the radical (CH3)3COO* is produced
      from the interaction of hypochlorite with (CH3)3COOH. Like Ce4+ but not Fe2+,
      hypochlorite addition to (CH3)3COOH was accompanied by a bright flash of
      chemiluminescence characteristic of the reactions in which peroxyl radicals are
      produced. Thus, all these results suggest peroxyl radical production in the
      reaction of hypochlorite with hydroperoxide. This reaction is one of the most
      possible ways for the initiation of free-radical LP that occurs in vivo, when
      hypochlorite interacts with unsaturated lipids comprising natural protein-lipid
      complexes, such as lipoproteins and biological membranes.

PMID- 12223088
TI  - Interaction of exogenous hypochlorite or hypochlorite produced by myeloperoxidase
      + H2O2 + Cl- system with unsaturated phosphatidylcholines.
AB  - The interaction between unsaturated phosphatidylcholines and either exogenous or
      endogenous (produced by the enzyme system involving myeloperoxidase (MPO), H2O2,
      and Cl-) hypochlorite was studied in multilayer liposomes containing oleic,
      linoleic, and arachidonic acid residues using MALDI-TOF mass spectrometry. At pH
      7.4, hypochlorite reacts with the double bond of the oleic acid residue in 1
      stearoyl-2-oleoyl-sn-glycero-3-phosphocholine producing oleic acid chlorohydrin
      as the main product. Minor amounts of glycols and epoxides were also detected.
      The main products of the reaction of hypochlorite with 1-stearoyl-2-linoleyl-sn
      glycero-3-phosphocholine were mono- and di-chlorohydrins of linoleic acid. The
      signals of monoglycol, epoxide, and glycol- or epoxide-containing
      monochlorohydrin derivatives were also present in the mass spectrum. The main
      products of the reaction of hypochlorite with 1-stearoyl-2-arachidonyl-sn-glycero
      3-phosphocholine were lysophosphatidylcholine (1-stearoyl-sn-glycero-3
      phosphocholine) and mono-, di-, and trichlorohydrin. Monoglycol and its
      derivatives containing one or two chlorohydrin groups were also detected. Along
      with those, carbonyl compounds (aldehyde and acid) formed as a result of double
      bond breakage in fifth position of arachidonate were detected. Monochlorohydrin
      was also found when liposomes comprising 1-stearoyl-2-oleoyl-sn-glycero-3
      phosphocholine were incubated in the presence of enzymatic mixture, MPO + H2O2 +
      Cl-, at pH 6.0. In the absence of the enzyme or either of its substrates (H2O2 or
      Cl-) or in the presence of the MPO inhibitor (sodium azide) or hypochlorite
      scavengers (taurine or methionine), monochlorohydrin formation was not observed.
      These data confirm the suggestion that just the hypochlorite generated in MPO
      catalysis provides for chlorohydrin formation. Thus, the use of MALDI-TOF mass
      spectrometry has shown, along with chlorohydrins, glycols and epoxides as the
      products of hypochlorite interaction with unsaturated phosphatidylcholines at
      physiological pH. It was first determined that hypochlorite breaks double bonds
      in polyunsaturated phosphatidylcholine and also causes lysophosphatidylcholine
      formation.

PMID- 12223089
TI  - Effects of oxygen on the dark recombination between photoreduced secondary
      quinone and oxidized bacteriochlorophyll in Rhodobacter sphaeroides reaction
      centers.
AB  - The influence of duration of exposure to actinic light (from 1 sec to 10 min) and
      temperature (from 3 to 35 degrees C) on the temporary stabilization of the
      photomobilized electron in the secondary quinone acceptor (QB) locus of
      Rhodobacter sphaeroides reaction centers (RC) was studied under aerobic or
      anaerobic conditions. Optical spectrophotometry and ESR methods were used. The
      stabilization time increased significantly upon increasing the exposure duration
      under aerobic conditions. The stabilization time decreased under anaerobic
      conditions, its dependence on light exposure duration being significantly less
      pronounced. Generation of superoxide radical in photoactivated aerobic samples
      was revealed by the ESR method. Possible interpretation of the effects is
      suggested in terms of interaction between the semiquinone QB with oxygen, the
      interaction efficiency being determined by the conformational transitions in the
      structure of RC triggered by actinic light on and off.

PMID- 12223090
TI  - Human plasma trans-sialidase donor and acceptor specificity.
AB  - Earlier we have isolated from human plasma desialylated low density lipoproteins
      (dLDL) and showed that, first, dLDL induce cholesterol esters accumulation--the
      main process accompanying atherosclerosis development. Second, the process of
      lipoprotein desialylation took place in plasma, and, finally, sialic acids
      removed from LDL are transferred to other serum glycoconjugates. In this study we
      have isolated from human plasma an enzyme transferring sialic acid residues
      (trans-sialidase) by affinity chromatography and studied its donor and acceptor
      specificity. Isolated enzyme in the presence of saccharide-acceptor can remove
      sialic acids from different lipoproteins, glycoproteins (fetuin, transferrin),
      and gangliosides (GM3, GD3, GM1, GD1a, GD1b). Plasma enzyme translocates alpha2
      6, alpha2-3 and to a lower extent alpha2-8 bonded sialic acids.
      Sialoglycoconjugates of human serum erythrocytes, serum lipoproteins,
      glycoproteins, and gangliosides can serve as donors of sialic acid for trans
      sialidase. Desialylated lipoproteins, especially dLDL, are more preferable sialic
      acid acceptors. Transferred sialic acid is found to be alpha2-6, alpha2-3, and
      alpha2-8 connected.

PMID- 12223091
TI  - Effects of osmolytes on unfolding of chicken liver fatty acid synthase.
AB  - Urea-induced aggregation of chicken liver fatty acid synthase [acyl-CoA:malonyl
      CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl-reducing and thioester
      hydrolyzing), EC 2.3.1.85] was studied. The aggregation was facilitated at
      increased ionic strength. Methyl-beta-cyclodextrin and some osmolytes, such as
      glycerol, sucrose, proline, glycine, and heparin, could effectively prevent the
      aggregation, implying an artificial chaperone role of those substances during
      fatty acid synthase unfolding. The osmolytes also protected the enzyme from
      inactivation.

PMID- 12223092
TI  - DNA binding activity of C/EBPbeta and C/EBPdelta for the rat alpha2-macroglobulin
      gene promoter is regulated in an acute-phase dependent manner.
AB  - Turpentine-induced acute-phase (AP) response in rats is followed by
      transcriptional activation of the alpha2-macroglobulin (MG) gene mediated by
      cytokine interleukin-6 (IL-6) and glucocorticoids. Based on nucleotide sequence
      analysis of the alpha2-MG gene promoter regions responsive to IL-6, we postulated
      that binding of members of the liver-enriched CCAAT-enhancer-binding proteins
      (C/EBP) family of transcription factors to the type I IL-6 responsive element (IL
      6RE) may participate in the transcriptional activation of this gene during AP
      response. Results of Western immunoblot and Northern-blot assays revealed
      coordinate changes in the pool levels of C/EBPalpha, -beta. and -delta protein
      isoforms and their genes expression in liver in response to turpentine. By means
      of an in vitro phosphorylation assay, South-Western blot, and selective
      proteolysis we have also found that only abilities of 35-kD C/EBPbeta and 27-kD
      C/EBPdelta to bind to the alpha2-MG gene promoter were affected by
      phosphorylation. Based on these data we concluded that transcriptional induction
      of the rat alpha2-MG gene during AP response correlates with both increased
      synthesis and phosphorylation-induced binding of 35-kD C/EBPbeta and 27-kD
      C/EBPdelta.

PMID- 12223093
TI  - Purification and characterization of biliverdin IXalpha from Atlantic salmon
      (Salmo salar) bile.
AB  - Biliverdin IXalpha was purified from the bile of Atlantic salmon (Salmo salar)
      using a silica gel (Wakogel C-200) column. The yield was 49.5 mg per 100 ml of
      fresh bile and purity 95.3%. The biliverdin IXalpha in the bile was quite stable
      when the bile was frozen at -80 degrees C for a period of 40 days. However, 7.1%
      of the biliverdin IXalpha was lost when the bile was stored at 4 degrees C for 20
      days. The purified biliverdin IXalpha appeared as a single spot with Rf value of
      0.25-0.27 on thin layer chromatography (TLC) and one main peak on high
      performance liquid chromatography (HPLC) at 436 or 650 nm. When the biliverdin
      IXalpha was subjected to enzymic reduction with highly purified biliverdin
      reductase, two clear isobestic points were seen, at 384 and 670 nm. When the
      products of the reaction with biliverdin IXalpha were extracted in butanol after
      completion of the reaction, one absorbance peak was observed at 468 nm. The time
      course of the reduction of biliverdin IXalpha to bilirubin IXalpha catalyzed by
      biliverdin reductase depended on reduced pyridine nucleotide. The time course of
      the NADPH-dependent reaction is different from that of the reaction with NADH. In
      the reduction of biliverdin IXalpha, per mole of biliverdin IXalpha reduced or
      per mole of bilirubin IXalpha formed 1 mole of reduced pyridine nucleotide was
      consumed in both the NADH and NADPH systems.

PMID- 12223094
TI  - Specific binding of integrin alphaIIbbeta3 to RGD peptide immobilized on a
      nitrilotriacetic acid chip: a surface plasmon resonance study.
AB  - Nitrilotriacetic acid has been routinely used in protein purification for its
      high affinity for His-tagged protein in the presence of Ni2+. Here we reported a
      type of nitrilotriacetic acid chip (NTA-chip) prepared by transferring NTA-DOGS
      containing a lipid monolayer to a 50 nm thick gold layer deposited on a glass
      slide. The surface binding ability of His-tagged protein and regeneration of NTA
      chip were characterized using a synthetic polypeptide P1 (His-His-His-His-His-His
      epsilon-aminohexanoic-Gly-Gly-Arg-Gly-Asp-Ser). The effect of divalent cations on
      integrin binding affinity for RGD ligand was investigated after P1 had been
      immobilized onto the sensor chip. The results show that the NTA-chip is a useful
      tool to immobilize His-tagged protein on the chip surface, and can provide a
      functional orientation for further investigation. The results also show that
      removing of Ca2+ bound on low affinity sites or adding of Mn2+ can increase the
      binding ability of integrin.

PMID- 12223095
TI  - Inactivation and dissociation of rice ribulose-1,5-bisphosphate
      carboxylase/oxygenase during denaturation by sodium dodecyl sulfate.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is a key enzyme in
      photosynthesis and photorespiration. The inactivation and subsequent
      conformational changes and dissociation of rice Rubisco by SDS have been studied.
      At low SDS concentrations (0.4 mM), Rubisco completely lost its carboxylase
      activity and most of its sulfhydryl groups became exposed. Dissociation of small
      subunits and significant conformational changes occurred at higher SDS
      concentrations. Increasing SDS concentrations caused only slight changes in CD
      spectrum, indicating no significant effect of SDS on the secondary structure of
      the enzyme. The results prove that the active site of Rubisco is more fragile to
      denaturants than the protein as a whole. The results also suggest that small
      subunits are more liable to SDS denaturation and thus dissociate first, while the
      more hydrophobic large subunits remain complexed. The naturally existing
      hydrophobic surface of Rubisco may be an important factor in the interaction of
      Rubisco with other macromolecules.

PMID- 12223096
TI  - Protective role of vitamin E on mefenamic acid-induced alterations in
      erythrocytes.
AB  - Erythrocyte osmotic fragility (O.F.), acetylcholinesterase (AChE) activity, and
      the level of malonyl dialdehyde (MDA) of control, mefenamic acid treated, and
      mefenamic acid with vitamin E treated rats were investigated. Administration of
      mefenamic acid to albino rats brought about a significant increase in the osmotic
      fragility of red cells and a significant (p < 0.01) decrease in the activity of
      AChE. We have also observed increased red cell level of MDA and decreased
      cholesterol (Chl), hemoglobin (Hb), and reduced glutathione (GSH) content.
      Supplementation of vitamin E to the mefenamic acid treated rats restored the
      O.F., AChE activity, level of MDA, and Chl, Hb, and GSH content almost to normal.
      These observations suggest that mefenamic acid causes functional impairment of
      red cell membrane, while vitamin E shows its protective role in maintaining
      normal red cell functions.

PMID- 12223097
TI  - Biosynthesis of chlorophyll from protochlorophyll(ide) in green plant leaves.
AB  - Using spectral methods, the biosynthesis of protochlorophyll(ide) and
      chlorophyll(ide) in green plant leaves was studied. The main chlorophyll
      precursors in the green leaves (as in etiolated leaves) were photoactive
      photocholorophyll(ide) forms Pchl(ide)655/650(448) and Pchl(ide)653/648(440). The
      contributions into Chl biosynthesis of the shorter-wavelength precursor forms,
      which were accumulated in darkened green leaves as well, were completely absent
      (of Pchl(ide) 633/628(440)) or insignificant (of Pchl(ide) 642/635(444)).

PMID- 12223098
TI  - The TATA-containing core promoter of the type II collagen gene (COL2A1) is the
      target of interferon-gamma-mediated inhibition in human chondrocytes: requirement
      for Stat1 alpha, Jak1 and Jak2.
AB  - Interferon-gamma (IFN-gamma) inhibits the synthesis of the cartilage-specific
      extracellular matrix protein type II collagen, and suppresses the expression of
      the type II collagen gene ( COL2A1 ) at the transcriptional level. To further
      examine this mechanism, the responses of COL2A1 regulatory sequences to IFN-gamma
      and the role of components of the Janus kinase/signal transducer and activators
      of transcription (JAK/STAT) pathway were examined in the immortalized human
      chondrocyte cell line, C-28/I2. IFN-gamma inhibited the mRNA levels of COL2A1 and
      aggrecan, but not Sox9, L-Sox5 and Sox6, all of which were expressed by these
      cells as markers of the differentiated phenotype. IFN-gamma suppressed the
      expression of luciferase reporter constructs containing sequences of the COL2A1
      promoter spanning -6368 to +125 bp in the absence and presence of the intronic
      enhancer and stimulated activity of the gamma-interferon-activated site (GAS)
      luciferase reporter vector, associated with induction of Stat1 alpha-binding
      activity in nuclear extracts. These responses to IFN-gamma were blocked by
      overexpression of the JAK inhibitor, JAK-binding protein (JAB), or reversed by
      dominant-negative Stat1 alpha Y701F containing a mutation at Tyr-701, the JAK
      phosphorylation site. IFN-gamma had no effect on COL2A1 promoter expression in
      Jak1 (U4A)-, Jak2 (gamma 2A)- and Stat1 alpha (U3A)-deficient cell lines. In the
      U3A cell line, the response to IFN-gamma was rescued by overexpression of Stat1
      alpha, but not by either Stat1 alpha Y701F or Stat1 beta. Functional analysis
      using deletion constructs showed that the IFN-gamma response was retained in the
      COL2A1 core promoter region spanning -45 to +11 bp, containing the TATA-box and
      GC-rich sequences but no Stat1-binding elements. Inhibition of COL2A1 promoter
      activity by IFN-gamma persisted in the presence of multiple deletions within the 
      45/+11 bp region. Our results indicate that repression of COL2A1 gene
      transcription by IFN-gamma requires Jak1, Jak2 and Stat1 alpha and suggest that
      this response involves indirect interaction of activated Stat1 alpha with the
      general transcriptional machinery that drives constitutive COL2A1 expression.

PMID- 12223099
TI  - The antioxidant (-)-epigallocatechin-3-gallate inhibits activated hepatic
      stellate cell growth and suppresses acetaldehyde-induced gene expression.
AB  - Activated hepatic stellate cells (HSC) are the primary source of excessive
      production of extracellular matrix during liver fibrogenesis. Although the
      underlying mechanisms remain incompletely understood, it is widely accepted that
      oxidative stress plays a critical role in liver fibrogenesis. Suppression of HSC
      growth and activation, as well as induction of apoptosis, have been proposed as
      therapeutic strategies for treatment and prevention of this disease. In the
      present report, we elucidated, for the first time, effects of the antioxidant (-)
      epigallocatechin-3-gallate (EGCG), a major (and the most active) component of
      green tea extracts, on cultured HSC growth and activation. Our results revealed
      that EGCG significantly inhibited cultured HSC growth by inducing cell cycle
      arrest and apoptosis in a dose- and time-dependent manner. In addition, EGCG
      markedly suppressed the activation of cultured HSC as demonstrated by blocking
      transforming growth factor-beta signal transduction and by inhibiting the
      expression of alpha1(I) collagen, fibronectin and alpha-smooth muscle actin genes
      induced by acetaldehyde, the most active metabolite of ethanol. Furthermore, EGCG
      reacted differently in the inhibition of nuclear factor-kappaB activity between
      cultured HSC with or without acetaldehyde stimulation. Taken together, our
      results indicated that EGCG was a novel and effective inhibitor for activated HSC
      growth and activation in vitro. Further studies are necessary to evaluate the
      effect of this polyphenol in prevention of quiescent HSC activation in vivo, and
      to further elucidate the underlying mechanisms.

PMID- 12223100
TI  - Acetaldehyde stimulates the activation of latent transforming growth factor-beta1
      and induces expression of the type II receptor of the cytokine in rat cultured
      hepatic stellate cells.
AB  - Acetaldehyde, the major active metabolite of alcohol, induces the activation of
      hepatic stellate cells (HSC), leading to over-production of alpha1(I) collagen
      and ultimately causing hepatic fibrosis. The underlying mechanisms of this
      process remain largely unknown. Transforming growth factor-beta1 (TGF-beta1) is a
      potent inducer of alpha1(I) collagen production. Accumulating evidence has shown
      a potential role for TGF-beta1 in alcohol-induced hepatic fibrogenesis. The aims
      of this study were to determine the effect of acetaldehyde on TGF-beta
      signalling, to elucidate the underlying mechanisms as well as to evaluate its
      role in expression of alpha1(I) collagen gene in cultured HSC. It was
      hypothesized that acetaldehyde activated TGF-beta signalling by inducing the
      expression of elements in the TGF-beta signal transduction pathway, which might
      contribute to alpha1(I) collagen gene expression in cultured HSC. Initial results
      revealed that acetaldehyde activated TGF-beta signalling in cultured HSC.
      Additional studies demonstrated that acetaldehyde stimulated the secretion and
      activation of latent TGF-beta1, and induced the expression of the type II TGF
      beta receptor (Tbeta-RII). Further experiments found cis - and trans -activating
      elements responsible for Tbeta-RII gene expression induced by acetaldehyde.
      Activation of TGF-beta signalling by acetaldehyde contributed to alpha1(I)
      collagen gene expression in cultured HSC. In summary, this report demonstrated
      that acetaldehyde stimulated TGF-beta signalling by increasing the secretion and
      activation of latent TGF-beta1 as well as by inducing the expression of Tbeta-RII
      in cultured HSC. Results from this report provided a novel insight into
      mechanisms by which acetaldehyde stimulated the expression of alpha1(I) collagen
      in HSC and a better understanding of effects of alcohol (or acetaldehyde) on
      hepatic fibrogenesis.

PMID- 12223101
TI  - The molecular mechanism of osteoclastogenesis in rheumatoid arthritis.
AB  - Bone-resorbing osteoclasts are formed from hemopoietic cells of the monocyte
      macrophage lineage under the control of bone-forming osteoblasts. We have cloned
      an osteoblast-derived factor essential for osteoclastogenesis, the receptor
      activator of NF-kappaB ligand (RANKL). Synovial fibroblasts and activated T
      lymphocytes from patients with rheumatoid arthritis also express RANKL, which
      appears to trigger bone destruction in rheumatoid arthritis as well. Recent
      studies have shown that T lymphocytes produce cytokines other than RANKL such as
      IL-17, granulocyte-macrophage colony-stimulating factor and IFN-gamma, which have
      powerful regulatory effects on osteoclastogenesis. The possible roles of RANKL
      and other cytokines produced by T lymphocytes in bone destruction are described.

PMID- 12223102
TI  - Autoantibody profiling for the study and treatment of autoimmune disease.
AB  - Proteomics technologies enable profiling of autoantibody responses using
      biological fluids derived from patients with autoimmune disease. They provide a
      powerful tool to characterize autoreactive B-cell responses in diseases including
      rheumatoid arthritis, multiple sclerosis, autoimmune diabetes, and systemic lupus
      erythematosus. Autoantibody profiling may serve purposes including classification
      of individual patients and subsets of patients based on their 'autoantibody
      fingerprint', examination of epitope spreading and antibody isotype usage,
      discovery and characterization of candidate autoantigens, and tailoring antigen
      specific therapy. In the coming decades, proteomics technologies will broaden our
      understanding of the underlying mechanisms of and will further our ability to
      diagnose, prognosticate and treat autoimmune disease.

PMID- 12223103
TI  - Cartilage-specific autoimmunity in animal models and clinical aspects in patients
      - focus on relapsing polychondritis.
AB  - Relapsing polychondritis is an autoimmune disease in which an inappropriate
      immune response destroys cartilage. Cartilage of the ears, larynx and nose rather
      than spine and joint cartilage is affected by a chronic relapsing and erosive
      inflammation. Several animal models for relapsing polychondritis have been
      published in which immunization with various cartilage proteins induces a variety
      of chondritis symptoms that mimic those seen in patients. In this review we
      describe the collagens, matrilin-1 and cartilage oligomeric matrix protein as
      potential autoantigens able to trigger the tissue-specific immune response seen
      both in patients and in animal models for relapsing polychondritis and related
      autoimmune diseases.

PMID- 12223104
TI  - Juvenile idiopathic arthritis genetics - what's new? What's next?
AB  - Studies have established the magnitude of the genetic basis of juvenile
      idiopathic arthritis (JIA). JIA is a complex genetic condition and the genes that
      influence susceptibility are actively being sought. A candidate gene approach is
      being used by several groups. MHC-, cytokine- and T-cell-related genes have all
      been positively associated with JIA. Here we review some of the latest genetic
      data, and discuss ways in which JIA genetic research might proceed.

PMID- 12223107
TI  - To keep the catch - that is the question: a personal account of the 3rd Annual
      EULAR Congress, Stockholm.
AB  - The 3rd Annual EULAR Congress, held in Stockholm on 12-15 June 2002, had a
      turnout of 8300 delegates, almost identical to last year's record attendance
      level in Prague. The venue was close to ideal, allowing ample space for poster
      sessions in the exhibition hall. The manned poster sessions were well attended,
      even on the last day of the Congress. The numerous invited speakers represented
      the world's elite, allowing the staging of excellent state-of-the-art podium
      sessions. The aim of attracting the young scientific community was partly
      achieved, but individual delegates' dependence on industry sponsorship poses
      potential problems. The organization was a big improvement compared to that of
      the two previous congresses. Approximately 1800 abstracts were submitted, an
      increase of 50%, resulting in a higher quality of accepted abstracts. The
      satellite symposia held every morning and late afternoon were well attended;
      thus, industry exposure of new products, both in podium sessions and at the
      exhibitions, was well accommodated. The Annual EULAR Congress consolidates its
      position as one of the two most important annual congresses of rheumatology, but
      EULAR economy and commercial aspects are still too dominant in relation to
      science.

PMID- 12223106
TI  - Genetics of osteoarticular disorders, Florence, Italy, 22-23 February 2002.
AB  - Osteoporosis (OP) and osteoarthritis (OA), the two most common age-related
      chronic disorders of articular joints and skeleton, represent a major public
      health problem in most developed countries. They are influenced by environmental
      factors and exhibit a strong genetic component. Large population studies clearly
      show their inverse relationship; therefore, an accurate analysis of the genetic
      bases of one of these two diseases may provide data of interest for the other
      disorder. The discovery of risk and protective genes for OP and OA promises to
      revolutionize strategies for diagnosing and treating these disorders. The primary
      goal of this symposium was to bring together scientists and clinicians working on
      OP and OA in order to identify the most promising and collaborative approaches
      for the coming decade. This meeting put into focus the importance of an adequate
      genetic approach to several areas of research: the search for the genetic
      determinants underlying new susceptibilities, the optimization of previously
      acquired data; the establishment of correlations between genetic polymorphism and
      functional variants, and gene-gene and gene-environment interactions
      (particularly those between genes and nutrients). An adequate genetic approach is
      also essential with regard to determining more selective criteria for phenotypic
      definition of familial OP, in order to obtain more homogeneous and statistically
      powerful family-based studies. The symposium concluded with an interesting
      overview of the future perspectives offered by DNA microarray technologies for
      identifying novel candidate genes, for developing proteomics and bioinformatics
      analyses and for designing low-cost clinical trials.

PMID- 12223105
TI  - Therapy of ankylosing spondylitis and other spondyloarthritides: established
      medical treatment, anti-TNF-alpha therapy and other novel approaches.
AB  - Therapeutic options for patients with more severe forms of spondyloarthritis
      (SpA) have been rather limited in recent decades. There is accumulating evidence
      that anti-tumor-necrosis-factor (anti-TNF) therapy is highly effective in SpA,
      especially in ankylosing spondylitis and psoriatic arthritis. The major anti-TNF
      alpha agents currently available, infliximab (Remicade(R)) and etanercept
      (Enbrel(R)), are approved for the treatment of rheumatoid arthritis (RA) in many
      countries. In ankylosing spondylitis there is an unmet medical need, since there
      are almost no disease-modifying antirheumatic drugs (DMARDs) available for
      severely affected patients, especially those with spinal manifestations. Judging
      from recent data from more than 300 patients with SpA, anti-TNF therapy seems to
      be even more effective in SpA than in rheumatoid arthritis. However, it remains
      to be shown whether patients benefit from long-term treatment, whether
      radiological progression and ankylosis can be stopped and whether long-term
      biologic therapy is safe.

PMID- 12223108
TI  - Cardiovascular risk in rheumatoid arthritis versus osteoarthritis: acute phase
      response related decreased insulin sensitivity and high-density lipoprotein
      cholesterol as well as clustering of metabolic syndrome features in rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) patients experience a markedly increased frequency of
      cardiovascular disease. We evaluated cardiovascular risk profiles in 79 RA
      patients and in 39 age-matched and sex-matched osteoarthritis (OA) patients.
      Laboratory tests comprised ultrasensitive C-reactive protein (CRP) and fasting
      lipids. Insulin sensitivity (IS) was determined by the Quantitative Insulin
      Sensitivity Check Index (QUICKI) in all OA patients and in 39 of the RA patients.
      Ten RA patients were on glucocorticoids. RA patients exercised more frequently
      than OA patients (chi2 = 3.9, P < 0.05). Nine RA patients and one OA patient had
      diabetes (chi2 = 4.5, P < 0.05). The median CRP, the mean QUICKI and the mean
      high-density lipoprotein (HDL) cholesterol were 9 mg/l (range, 0.5-395 mg/l),
      0.344 (95% confidence interval [CI], 0.332-0.355) and 1.40 mmol/l (95% CI, 1.30
      1.49 mmol/l) in RA patients, respectively, as compared with 2.7 mg/l (range, 0.3
      15.9 mg/l), 0.369 (95% CI, 0.356-0.383) and 1.68 mmol/l (95% CI, 1.50-1.85
      mmol/l) in OA patients. Each of these differences was significant (P < 0.05).
      After controlling for the CRP, the QUICKI was similar in RA and OA patients (P =
      0.07), while the differences in HDL cholesterol were attenuated but still
      significant (P = 0.03). The CRP correlated with IS, while IS was associated with
      high HDL cholesterol and low triglycerides in RA patients and not in OA patients.
      A high CRP (>/= 8 mg/l) was associated with hypertension (chi2 = 7.4, P < 0.05)
      in RA patients. RA glucocorticoid and nonglucocorticoid users did not differ in
      IS and lipids (P > 0.05). Excess cardiovascular risk in RA patients as compared
      with OA patients includes the presence of decreased IS and HDL cholesterol in RA
      patients. The latter is only partially attributable to the acute phase response.
      The CRP, IS, HDL cholesterol, triglycerides and hypertension are inter-related in
      RA patients, whereas none of these relationships were found in OA patients.

PMID- 12223109
TI  - Lack of autoantibody production associated with cytomegalovirus infection.
AB  - To confirm an association between cytomegalovirus (CMV) infection and the
      presence of antibodies to Smith (Sm), to ribonucleoprotein (RNP), and to a
      component of the U1 ribonucleoproteins (U1-70 kD), we measured antibodies to
      these protein antigens using an enzyme immunoassay and an immunoblot. The
      antibodies were measured in the sera of 80 healthy subjects, one-half of whom
      were naturally CMV seropositive and one-half were CMV seronegative, and in eight
      subjects immunized with a live attenuated strain of CMV. None of the vaccinees
      developed antibodies to Sm, to RNP, or to U1-70 kD at either 4 or 12 months after
      immunization. Additionally, there was no statistically significant association
      between levels of antibodies to Sm or to RNP and between sera obtained from
      vaccinees, natural CMV seropositive individuals, and CMV seronegative
      individuals. One CMV seropositive serum and one CMV seronegative serum tested
      positive for antibodies to U1-70 kD. These data indicate that neither wild-type
      infection nor the live-attenuated Towne vaccine frequently induce autoantibody
      production.

PMID- 12223110
TI  - Anti-TNF-alpha antibody allows healing of joint damage in polyarthritic
      transgenic mice.
AB  - Anti-tumor-necrosis-factor-alpha (TNF-alpha) monoclonal antibody was used to
      treat Tg197 transgenic mice, which constitutively produce human TNF-alpha (hTNF
      alpha) and develop a progressive polyarthritic disease. Treatment of both young
      (7- or 8-week-old) and aged (27- or 28-week-old) mice commenced when at least two
      limbs showed signs of moderate to severe arthritis. The therapeutic efficacy of
      anti-TNF-alpha antibody was assessed using various pathological indicators of
      disease progression. The clinical severity of arthritis in Tg197 mice was
      significantly reduced after anti-TNF-alpha treatment in comparison with saline
      treated mice and in comparison with baseline assessments in both young and aged
      mice. The treatment with anti-TNF-alpha prevented loss of body weight.
      Inflammatory pathways as reflected by elevated circulating hTNF-alpha and local
      expression of various proinflammatory mediators were all diminished by anti-TNF
      alpha treatment, confirming a critical role of hTNF-alpha in this model of
      progressive polyarthritis. More importantly, the amelioration of the disease was
      associated with reversal of existing structural damage, including synovitis and
      periosteal bone erosions evident on histology. Repair of cartilage was age
      dependent: reversal of cartilage degradation after anti-TNF-alpha treatment was
      observed in young mice but not in aged mice.

PMID- 12223111
TI  - Molecular profile of synovial fibroblasts in rheumatoid arthritis depends on the
      stage of proliferation.
AB  - The aim of this study was to explore the molecular profile of proliferating
      rheumatoid arthritis synovial fibroblasts (RA-SF). Total RNA was extracted from
      two cultures of RA-SF (low-density [LD] proliferating cells and high-density [HD]
      nonproliferating cells) and suppression subtractive hybridization was performed
      to compare differential gene expression of these two cultures. Subtracted cDNA
      was subcloned, and nucleotide sequences were analyzed to identify each clone.
      Differential expression of distinct clones was confirmed by semiquantitative RT
      PCR. The expression of certain genes in synovial tissues was examined by in situ
      hybridization. In both LD and HD cells, 44 clones were upregulated. Of the 88
      total clones, 46 were identical to sequences that have previously been
      characterized. Twenty-nine clones were identical to cDNAs that have been
      identified, but with unknown functions so far, and 13 clones did not show any
      significant homology to sequences in GenBank (NCBI). Differential expression of
      distinct clones was confirmed by RT-PCR. In situ hybridization showed that
      certain genes, such as S100A4, NFAT5, unr and Fbx3, were also expressed
      predominantly in synovial tissues from patients with RA but not from normal
      individuals. The expression of distinct genes in proliferating RA-SF could also
      be found in RA synovium, suggesting that these molecules are involved in synovial
      activation in RA. Most importantly, the data indicate that the expression of
      certain genes in RA-SF depends on the stage of proliferation; therefore, the
      stage needs to be considered in any analysis of differential gene expression in
      SF.

PMID- 12223112
TI  - Regulation of CD154-induced interleukin-12 production in synovial fluid
      macrophages.
AB  - Interleukin (IL)-12, being a major cytokine that induces T helper (Th) 1
      differentiation and inflammatory response, has been postulated to be an important
      mediator of synovial inflammation in rheumatoid arthritis (RA). However, the
      regulation of IL-12 production in RA has not been elucidated. Our knowledge is
      mainly based on studies of the production of IL-12p40 and not the functional IL
      12p70 heterodimer. We have studied the CD154-induced IL-12p40 and IL-12p70
      production by synovial fluid (SF) macrophages from patients with RA. CD40
      ligation induced the secretion of IL-12p40 but not IL-12p70. The observed
      increase in IL-10 and tumor necrosis factor (TNF)-alpha production indicated that
      SF macrophages responded to CD40 ligation. The expression of p40 mRNA was
      increased significantly and remained upregulated after CD40 ligation, whereas the
      increase of p35 transcript expression was observed only transiently and at a
      lower level. We further observed that dendritic cells (DCs) derived in vitro from
      SF macrophages produced IL-12p70. Most importantly, IL-4 and IL-13 primed SF
      macrophages to produce IL-12p70, whereas IFN-gamma was not observed to activate
      IL-12p70 production in these cells, in contrast with normal peripheral blood
      monocytes. These results provide novel information about the regulation of IL
      12p70 production and the function of the cytokine network in RA.

PMID- 12223113
TI  - Gender and HIV-associated pulmonary tuberculosis: presentation and outcome at one
      year after beginning antituberculosis treatment in Uganda.
AB  - BACKGROUND: Tuberculosis is responsible for more female deaths around the earth
      than any other infectious disease. Reports have suggested that responses to
      tuberculosis may differ between men and women. We investigated gender related
      differences in the presentation and one year outcomes of HIV-infected adults with
      initial episodes of pulmonary tuberculosis in Uganda. METHODS: We enrolled and
      followed up a cohort of 105 male and 109 female HIV-infected adults on treatment
      for initial episodes of culture-confirmed pulmonary tuberculosis between March
      1993 and March 1995. A favorable outcome was defined as being cured and alive at
      one year while an unfavorable outcome was not being cured or dead. Subjects were
      followed-up by serial medical examinations, complete blood counts, serum beta2
      microglobulin, CD4+ cell counts, sputum examinations, and chest x-rays. RESULTS:
      Male patients were older, had higher body mass indices, and lower serum beta2
      microglobulin levels than female patients at presentation. At one year, there was
      no difference between male and female patients in the likelihood of experiencing
      a favorable outcome (RR 1.02, 95% CI 0.89-1.17). This effect persisted after
      controlling for symptoms, serum beta2 microglobulin, CD4+ cell count, and
      severity of disease on chest x-ray (OR 1.07, 95% CI 0.54-2.13) with a repeated
      measures model. CONCLUSIONS: While differences existed between males and females
      with HIV-associated pulmonary tuberculosis at presentation, the outcomes at one
      year after the initiation of tuberculosis treatment were similar in Uganda. Women
      in areas with a high HIV and tuberculosis prevalence should be encouraged to
      present for screening at the first sign of tuberculosis symptoms.

PMID- 12223114
TI  - Impact of HIV vaccination on laboratory diagnosis: case reports.
AB  - BACKGROUND: It has not been clearly demonstrated whether HIV vaccination can
      complicate routine HIV testing. In this report, we describe the laboratory data
      of two prisoners who received rgp120 vaccine in a phase III trial underway in
      Thailand. These data indicate that previous vaccination may complicate the
      interpretation of screening HIV diagnostic tests. CASE PRESENTATION: The
      participants were identified from a cohort study on "Health factors related to
      HIV-1 and other viral infections among incarcerated people" that was approved by
      The Ethical Committee for Research in Human Subjects, Ministry of Public Health,
      Thailand. HIV diagnosis was definitively established with serial specimens using
      multi-screening tests, Western blot and diagnostic PCR.Anti-HIV screening tests
      consistently exhibited either weakly reactive or inconclusive results. The band
      patterns of the Western blot analysis corresponded to those found in individuals
      who received the rgp120 vaccination. Definite results were established using
      diagnostic PCR, which exhibited consistently negative results with follow-up
      specimens. Such problems in HIV testing are not easily resolved in the routine
      clinical setting in Thailand. CONCLUSIONS: These data demonstrate that HIV-1
      vaccination interferes with routine diagnostic tests. Similar cases will not be
      uncommon in Thailand, where 2,545 people have already participated in a phase III
      trial.

PMID- 12223115
TI  - cagA and vacA in strains of Helicobacter pylori from ulcer and non-ulcerative
      dyspepsia patients.
AB  - BACKGROUND: The cytotoxin associated gene A (cagA), and the vacuolating cytotoxin
      gene A (vacA) of Helicobacter pylori have been associated to phenotypic
      characteristics of virulence. The objectives of this study were to detect the
      presence of cagA and to characterize the allelic variants of vacA in 63 strains
      of H. pylori isolated from colonized individuals with different clinical
      outcomes. METHODS: 38 strains were isolated from patients with non-ulcerative
      dyspepsia (NUD) and 25 were isolated from colonized individuals with peptic
      ulcers. The genotypic characterization was carried out utilizing PCR methodology.
      The presence of the cagA gene was detected using two set of primers from the
      middle conservative region of the cagA, and primers for the signal and middle
      region were used for the genotyping of vacA. RESULTS: The presence of cagA showed
      similar rates in strains from peptic ulcers (60%) and NUD patients (55%). Also
      similar was the prevalence of the allelic form s1 of vacA between the strains
      obtained from ulcers or NUD patients. However, the combination cagA+/vacA s1m1
      was found more frequently among the H. pylori strains from peptic ulcer patients
      (52%) than among strains isolated from NUD patients (26%), this difference was
      statistically significant (p = 0.035). CONCLUSIONS: The presence of either cagA
      or the allelic variant s1 vacA alone do not have a predictive value as as a risk
      markers of severe gastric pathologies in the Chilean population. However, being
      infected by a H. pylori strain with the genotype cagA+/vacA s1m1 may be
      associated to an increased risk of acquiring a peptic ulcer disease.

PMID- 12223116
TI  - Little qualitative RNA misexpression in sterile male F1 hybrids of Drosophila
      pseudoobscura and D. persimilis.
AB  - BACKGROUND: Although the genetics of hybrid sterility has been the subject of
      evolutionary studies for over sixty years, no one has shown the reason(s) why
      alleles that operate normally within species fail to function in another genetic
      background. Several lines of evidence suggest that failures in normal gene
      transcription contribute to hybrid dysfunctions, but genome-wide studies of gene
      expression in pure-species and hybrids have not been undertaken. Here, we study
      genome-wide patterns of expression in Drosophila pseudoobscura, D. persimilis,
      and their sterile F1 hybrid males using differential display. RESULTS: Over five
      thousand amplifications were analyzed, and 3312 were present in amplifications
      from both of the pure species. Of these, 28 (0.5%) were not present in
      amplifications from adult F1 hybrid males. Using product-specific primers, we
      were able to confirm one of nine of the transcripts putatively misexpressed in
      hybrids. This transcript was shown to be male-specific, but without detectable
      homology to D. melanogaster sequence. CONCLUSION: We tentatively conclude that
      hybrid sterility can evolve without widespread, qualitative misexpression of
      transcripts in species hybrids. We suggest that, if more misexpression exists in
      sterile hybrids, it is likely to be quantitative, tissue-specific, and/ or
      limited to earlier developmental stages. Although several caveats apply, this
      study was a first attempt to determine the mechanistic basis of hybrid sterility,
      and one potential candidate gene has been identified for further study.

PMID- 12223117
TI  - Individual variation evades the prisoner's dilemma.
AB  - BACKGROUND: The Prisoner's Dilemma (PD) is a widely used paradigm to study
      cooperation in evolutionary biology, as well as in fields as diverse as moral
      philosophy, sociology, economics and politics. Players are typically assumed to
      have fixed payoffs for adopting certain strategies, which depend only on the
      strategy played by the opponent. However, fixed payoffs are not realistic in
      nature. Utility functions and the associated payoffs from pursuing certain
      strategies vary among members of a population with numerous factors. In biology
      such factors include size, age, social status and expected life span; in
      economics they include socio-economic status, personal preference and past
      experience; and in politics they include ideology, political interests and public
      support. Thus, no outcome is identical for any two different players. RESULTS: We
      show that relaxing the assumption of fixed payoffs leads to frequent violations
      of the payoff structure required for a Prisoner's Dilemma. With variance twice
      the payoff interval in a linear PD matrix, for example, only 16% of matrices are
      valid. CONCLUSIONS: A single player lacking a valid PD matrix destroys the
      conditions for a Prisoner's Dilemma, so between any two players, PD games
      themselves are fewer still (3% in this case). This may explain why the Prisoner's
      Dilemma has hardly been found in nature, despite the fact that it has served as a
      ubiquitous (and still instructive) model in studies of the evolution of
      cooperation.

PMID- 12223118
TI  - IkB kinase alpha: a link in the chain of the mammary cycle.
AB  - The transcription factor NF-kappaB exhibits altered activity in some breast
      cancers but the relevance of this association has not been established. Cao et
      al.'s elegant study recently published in Cell reveals a NF-kappaB-dependent
      signalling pathway responsible for epithelial proliferation in the mouse mammary
      gland. Could this mechanism, rather than prevention of apoptosis, be responsible
      for the reported association between NF-kappaB and breast cancer? Could the
      specificity of NF-kappaB modulators of the IkB kinase complex determine the fate
      of epithelial cells at different stages of mammary development?

PMID- 12223119
TI  - A new model for ductal carcinoma in situ suggests strategies for treatment.
AB  - Human ductal carcinoma in situ (DCIS) of the breast is now diagnosed quite
      frequently, due largely to the introduction of mammographic screening. It has
      been shown in a cell culture system that activation of c-erbB-2, but not the
      epidermal growth factor receptor, results in a DCIS-like phenotype. Since
      overexpression of c-erbB-2 occurs in 60% of DCIS, this suggests that it could be
      a target for treatment in this disease.

PMID- 12223120
TI  - Familial risks of breast cancer.
AB  - A recent analysis by the Collaborative Group on Hormonal Factors in Breast Cancer
      has provided the most precise quantification to date of the familial risks of
      breast cancer. The familial relative risks are shown to decrease from more than
      fivefold in women younger than age 40 years with a first-degree relative aged
      younger than 40 years at diagnosis, to 1.4-fold in women older than 60 years with
      a relative diagnosed over age 60 years. These risks increase progressively with
      the number of affected relatives. The risks associated with an affected mother
      and an affected sister are similar, and the relative (but not absolute) risks are
      similar in subgroups defined by other established breast cancer risk factors.
      These results provide a useful basis for counselling of women with a family
      history of breast cancer, and they have implications for the genetic basis of the
      disease.

PMID- 12223121
TI  - Progesterone receptors - animal models and cell signaling in breast cancer: Role
      of steroid receptor coactivators and corepressors of progesterone receptors in
      breast cancer.
AB  - Progesterone, an ovarian steroid hormone, plays a key role in the development and
      function of the mammary gland, as it also does in the uterus and the ovary. The
      action of progesterone is mediated through its intracellular cognate receptor,
      the progesterone receptor (PR), which functions as a transcription factor that
      regulates gene expression. As with other nuclear receptors, coregulators
      (coactivators and corepressors) recruited by the liganded or unliganded PR,
      either to enhance or to suppress transcription activity, modulate the function of
      the PR. Mutation or aberrant expression of the coregulators might thus affect the
      normal function of the PR and hence disrupt the normal development of the mammary
      gland, which may lead to breast cancer.

PMID- 12223122
TI  - Expression and transcriptional activity of progesterone receptor A and
      progesterone receptor B in mammalian cells.
AB  - Progesterone is an essential regulator of normal female reproductive function.
      Its effects are mediated by two nuclear progesterone receptor (PR) proteins, PRA
      and PRB, which are identical except for an additional 164 amino acids at the N
      terminal end of PRB. Transcriptional analyses of the two receptor forms have
      assigned strikingly distinct functional signatures to the two PRs, despite their
      apparent physical similarity. The basis of these differences is yet to be fully
      understood. Furthermore, these differences are strongly influenced by the cell
      type and the promoter used. We review the mammalian transcriptional studies of
      PRA and PRB, and compare them with what is known about their expression and
      function in target tissues.

PMID- 12223123
TI  - Progesterone's role in mammary gland development and tumorigenesis as disclosed
      by experimental mouse genetics.
AB  - The progesterone receptor knockout mouse demonstrated progesterone's importance
      to parity-induced mammary tertiary branching and lobuloalveologenesis. Because
      early parity provides significant protection against breast cancer whereas
      prolonged exposure to premenopausal ovarian progesterone (or to postmenopausal
      supplementations thereof) has been linked to breast cancer risk, this steroid can
      be considered to exhibit contrasting roles in breast cancer etiology. This review
      describes the important mouse models that have contributed to our understanding
      of progesterone's role in mammary gland development and neoplasia. We conclude by
      emphasising the urgent need to identify the molecular targets of the progesterone
      receptor, and to determine whether these targets are modulated differently by the
      progesterone receptor isoforms (A and B) during mammary morphogenesis and
      tumorigenesis.

PMID- 12223124
TI  - The role of oestrogen and progesterone receptors in human mammary development and
      tumorigenesis.
AB  - A relatively small number of cells in the normal human mammary gland express
      receptors for oestrogen and progesterone (ER and PR), and there is almost
      complete dissociation between steroid receptor expression and proliferation.
      Increased expression of the ER alpha (ERalpha) and loss of the inverse
      relationship between receptor expression and proliferation occur at the very
      earliest stages of tumorigenesis, implying that dysregulation of ERalpha
      expression contributes to breast tumour formation. There is evidence also for
      alterations in the ratio between the two PR isoforms in premalignant breast
      lesions. Elucidation of the factors mediating the effects of oestradiol and
      progesterone on development of the normal breast and of the mechanisms by which
      expression of the ERalpha and the PR isoforms is controlled could identify new
      targets for breast cancer prevention and improved prediction of breast cancer
      risk.

PMID- 12223125
TI  - British Cancer Research Meeting, 30 June-3 July 2002, Glasgow.
AB  - The 2002 British Cancer Research Meeting was held from 30th June to 3rd July in
      Glasgow, UK. The meeting was structured to include educational workshops, plenary
      lectures, symposia, and poster sessions, which brought together scientists and
      clinicians. Presentations ranged from the impact that modifications to basic
      chromatin structure can have on diagnosis and targeted gene therapy, to the
      outcome of novel therapeutics through clinical trials. The emphasis was clear:
      patient survival is the main priority and treatment of organ-specific cancer must
      inevitably be replaced by individualised tumour-specific therapy.

PMID- 12223126
TI  - Tumour Fas ligand:Fas ratio greater than 1 is an independent marker of relative
      resistance to tamoxifen therapy in hormone receptor positive breast cancer.
AB  - BACKGROUND: The objective of the present study was to examine the prognostic and
      predictive significance of the apoptosis-related marker Fas ligand (FasL):Fas
      ratio in breast cancer. METHODS: Tumour biopsies from 215 primary invasive breast
      cancer patients were examined for the expression of FasL and Fas mRNA transcripts
      by quantitative real-time RT-PCR. Their prognostic and predictive impact on
      patient survival was determined in univariate and multivariate survival analyses.
      RESULTS: Using a cutoff value of 1, a FasL:Fas ratio greater than 1 was found to
      have significant prognostic value for disease-free survival among the total
      population (median follow up 54 months). It was associated with a significantly
      decreased disease-free survival (P = 0.022) and with a tendency toward increased
      mortality (P = 0.14) in univariate analysis. Hormone receptor positive women
      exclusively treated with tamoxifen (n = 86) and with a FasL:Fas ratio greater
      than 1 had a significantly decreased disease-free survival (P = 0.008) and
      overall survival (P = 0.03) in univariate Kaplan-Meier analysis. Furthermore,
      tumour size and FasL:Fas ratio were of independent predictive significance in the
      multivariate model for disease-free and overall survival in that subgroup. Among
      postmenopausal patients (n = 148) both of those factors retained independent
      prognostic significance in the multivariate model for disease-free survival. In
      contrast, FasL:Fas ratio had no significant predictive value in patients
      exclusively treated with chemotherapy. CONCLUSION: The data presented indicate
      that FasL:Fas ratio may be useful not only as a prognostic factor but also as a
      predictive factor for projecting response to the antioestrogen tamoxifen. The
      results strongly support a correlation between FasL:Fas ratio greater than 1 and
      lack of efficacy of tamoxifen in hormone receptor positive patients.

PMID- 12223127
TI  - Risk factors for breast cancer in Iran: a case-control study.
AB  - BACKGROUND: Iranian breast cancer patients are relatively younger than their
      Western counterparts. The objective of the present study was to investigate risk
      factors for breast cancer in Iranian women. METHOD: A case-control study was
      conducted from April 1997 to April 1998 in Tehran, Iran. Demographical data and
      risk factor related information were collected using a short structured
      questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived
      from logistic regression analysis. RESULTS: In all, 286 women with breast cancer
      and 249 control women were interviewed. In multivariate analysis, only marital
      status (never married: OR 4.24, 95% CI 1.70-10.57 [P = 0.002]; widowed/divorced:
      OR 1.71, 95% CI 1.05-2.68 [P = 0.03]) and family history (positive family history
      of breast cancer: OR 2.95, 95% CI 1.15-7.59 [P = 0.02]) were associated with
      significantly increased risk for breast cancer. CONCLUSION: The findings of the
      present study suggest that family history and marital status may have an impact
      on the incidence of breast cancer in Iranian women.

PMID- 12223128
TI  - Impact of false-positive mammography on subsequent screening attendance and risk
      of cancer.
AB  - BACKGROUND: One area of concern within the largely successful UK National Health
      Service breast screening programme is the relatively high proportion of women
      showing mammographic abnormalities who undergo further diagnostic tests that
      prove negative. Previous studies suggest that, in addition to increasing anxiety,
      such false-positive mammography is associated with increased risk of subsequent
      interval cancer. In the present article, we quantify this increased risk,
      investigate whether it extends to cancers detected at rescreening, and determine
      whether cancers differ between women who have, and have not, experienced false
      positive mammography. METHODS: This was a retrospective cohort study of 140,387
      women aged 49-63 years routinely invited for first screening by the East Anglian
      National Health Service breast screening programme. Proportions reattending, and
      subsequent risk and pathological attributes of cancer were compared between women
      who underwent further (negative) assessment following false-positive mammography
      and women mammographically normal at first screen. RESULTS: At first screen,
      108,617 (91.9%) of the screened women were mammographically normal, 4278 (3.6%)
      were assessed and then judged normal, and 514 (0.4%) underwent benign biopsy.
      Compared with nonassessed normal women, reattendance was lower among assessed
      women: 83.1% (95% confidence interval [CI], 82.0-84.1) versus 85.7% (95% CI, 85.5
      85.9) (odds ratio [OR], 0.82; 95% CI, 0.76-0.89). Assessed women were at greater
      risk of interval cancer (rate per 1000 women screened, 9.6 [95% CI, 6.8-12.4]
      versus 3.0 [95% CI, 2.7-3.4]; OR, 3.19 [95% CI, 2.34-4.35]), and also of cancer
      detected at second screen (rate per 1000, 8.4 [95% CI, 5.8-10.9] versus 3.9 [95%
      CI, 3.5-4.3]; OR, 2.15 [95% CI, 1.55-2.98]). More cancers in assessed women
      measured >or = 20 mm (OR, 1.59; 95% CI, 0.99-2.55). CONCLUSIONS: Women undergoing
      false-positive mammography at first screen were less likely to reattend for
      subsequent screens than were nonassessed women, yet they were more likely to
      develop interval cancers or cancers at second screen, and their cancers were
      larger. Factors predisposing for false-positive mammography require
      investigation. Women should be encouraged to continue with screening.

PMID- 12223129
TI  - [DNA chips and their use in diagnosis of liver diseases].

PMID- 12223130
TI  - [Transient expression of fusion protein with a chimeric HBsAg-HSP70 construct in
      HepG2 cells].
AB  - OBJECTIVE: To investigate transient expression of fusion protein with a chimeric
      HBsAg-HSP70 construct in HepG2 cells. METHODS: Enkaryotic expression plasmids
      inserted HBsAg gene or chimeric HBsAg-HSP70 gene were prepared and transfected
      into HepG2 cells by means of cationic liposome. mRNA were detected by RT-PCR and
      proteins expressed in the cells were detected by immunocytochemistry 48 hours
      later. HBsAg in cultured supernatants and cell lysates were assayed by ELISA.
      RESULTS: Fusion protein (HBsAg-HSP70) transient expression in HepG2 cells were
      confirmed by RT-PCR, immunocytochemistry or ELISA, but fusion protein was not
      assayed in cell cultured supernatants by ELISA. CONCLUSIONS: Transfection of
      HepG2 cells with a chimeric HBsAg-HSP70 construct leads to express fusion
      protein, but it does not secrete into cell cultured supernatants.

PMID- 12223131
TI  - [Chronobiologic contrast of expression of p53, p16, and cyclin D1 in
      hepatocarcinoma cells].
AB  - OBJECTIVE: To contrast the feature of different periods of p53, p16, and cyclin
      D1 expression in cells of hepatocarcinoma. METHODS: Sixty hepatocarcinoma
      specimens were collected and divided into three periods in one yearly cycle with
      each period of 20 cases. Hepatocellular carcinoma was documented in all cases by
      pathomorphological classification. Edmondson-Steinet grading belonged to II~III
      stages. The expression of gene proteins of p53, p16, and cyclin D1 was determined
      by immunohistochemical assay (S-P method). The expressive intensity was analysed
      by the rank test. RESULTS: p16 expression showed significant difference of period
      (H=10.334, P<0. 05). Arpil-July was the high expressive period. CONCLUSIONS: p16
      may take an important role in the chronobiologic mechanism of gene control of
      hepatocyte canceration and hepatocarcinoma cell growth.

PMID- 12223132
TI  - [Rapid induction of mRNAs for liver regeneration genes by hepatopoietin and
      partial hepatectomy].
AB  - OBJECTIVE: To investigate the effect of recombinant human hepatopoietin (rhHPO)
      and partial hepatectomy on rapidly induced expression of immediate early gene.
      METHODS: We investigated the different gene expression within 1 hour after 2/3
      partial hepatectomy by representational difference analysis and in primary
      cultured hepatocytes system. RESULTS: In the expressed sequence tag (EST)
      library, we identified that most of these genes were immediate early gene, and
      found one new gene PC3 that might be associated to liver regeneration in the EST
      library. Moreover, PC3 gene was rapidly induced after 2/3 partial hepatectomy and
      the expressing peak was within 1~2 hours after operation. HPO can rapidly induce
      the expression of these genes (c-fos, LRF-1, and PC3, etc.) in primarily cultured
      rat hepatocyte, which might be one of HPO molecular mechanism on stimulating
      hepatocyte proliferation. CONCLUSIONS: rhHPO and partial hepatectomy can rapidly
      induce the expression of immediate early gene. PC3 gene is immediate early gene
      related to liver regeneration.

PMID- 12223133
TI  - [Anti-HBV effects of genetically engineered replication-defective HBV with
      combined expression of antisense RNA and dominant negative mutants of core
      protein and construction of first-generation packaging cell line for HBV vector].
AB  - OBJECTIVE: To explore the possibility of using HBV as a gene delivery vector, and
      to test the anti-HBV effects by intracellular combined expression of antisense
      RNA and dominant negative mutants of core protein. METHODS: Full length of mutant
      HBV genome, which expresses core-partial P fusion protein and/or antisense RNA,
      was transfected into HepG2.2.15 cell lines. Positive clones were selected and
      mixed in respective groups with hygromycin in the culture medium. HBsAg and
      HBeAg, which exist in the culture medium, were tested by ELISA method.
      Intracellular HBc related HBV DNA was examined by dot blot hybridization. The
      existence of recombinant HBV virion in the culture medium was examined by PCR.
      Free of packaging signal, HBV genome, which express the HBV structural proteins
      including core, pol and preS/S proteins, was inserted into pCI-neo vector. HepG2
      cell lines were employed to transfect with the construct. G418 selection was done
      at the concentration of 400mug/ml in the culture medium. The G418-resistant
      clones with the best expression of HBsAg and HBcAg were theoretically considered
      as packaging cell lines and propagated under the same conditions. It was
      transfected with plasmid pMEP-CPAS and then selected with G418 and hygromycin in
      the culture medium. The existence of recombinant HBV virion in the culture medium
      was examined by PCR. RESULTS: The mean inhibitory rates of HBsAg were 2.74%
      3.83%, 40.08 2.05% (t=35.5, P<0.01), 66.54% 4.45% (t=42.3, P<0.01), and 73.68%
      5.07% (t=51.9, P<0.01) in group 2.2.15-pMEP4, 2.2.15-CP, 2.2.15-SAS, and 2.2.15
      CPAS, respectively. The mean inhibitory rates of HBeAg were 4.46% 4.25%, 52.86%
      1.32% (t=36.2, P<0.01), 26.36% 1.69% (t=22.3, P<0.01), and 59.28% 2.10% (t=39.0,
      P<0.01), respectively. The inhibitory rates of HBc related HBV DNA were 0, 82.0%,
      59.9%, and 96.6%, respectively. Recombinant HB virion was detectable in the
      culture medium of all the three treatment groups. G418-resistant HBV packaging
      cell line, which harbored an HBV mutant whose packaging signal had been deleted,
      was generated. Expression of HBsAg and HBcAg was detectable. Transfected with
      plasmid pMEP-CPAS, it was found to secrete recombinant HB virion and no wild-type
      HBV was detectable in the culture medium. CONCLUSIONS: It has stronger anti-HBV
      effects by combined expression of antisense RNA and dominant negative mutants
      than by individual expression of them. With the help of wild-type HBV, the
      modified HBV genome can form and secret HBV like particles, which provides
      evidence that the antiviral gene will be hepatotropic expression and the
      antiviral effects will be amplified. The packaging cell line can provide
      packaging for replication-defective HBV, but with low efficiency.

PMID- 12223134
TI  - [Effects of IH764-3 on proliferation and apoptosis of HSCs].

PMID- 12223135
TI  - [Epitope mapping of hepatitis C virus non-structure protein 5 from a 7 peptide
      phage library by using immobilized specific monoclonal antibody].
AB  - OBJECTIVE: To screen HCV NS5 mimotopes by using monoclonal antibody and phage
      peptide library. METHODS: By using HCV NS5 monoclonal antibody as selective
      molecule, a 7 peptide phage library was biopanned and positive clones were
      selected by ELISA, competition assay and DNA sequencing. RESULTS: Twelve positive
      clones were chosen for DNA sequencing. From the experiment and sequencing
      comparison results, one epitope was confirmed as the mimotope of HCV NS5.
      CONCLUSIONS: HCV mimotope is obtained by phage peptide library screening. The
      result provides a new approach for HCV therapy and vaccine development.

PMID- 12223136
TI  - [Relationship between the quantities of virus and the models of serologic markers
      in patients infected with HBV].
AB  - OBJECTIVE: To explore the relationship between the quantities of HBV and the
      models of serologic markers. METHODS: Real-time fluorescent quantitative PCR was
      used to measure the HBV DNA and ELISA was used to detect the antigen/antibody of
      HBV. RESULTS: The patients whose HBV copies were more than 10(3)/ml accounted for
      87.3%, whose copies were more than 10(7)/ml accounted for 66.7% among the HBsAg
      and HBeAg -positive patients. The patients whose HBV copies were less than
      10(3)/ml accounted for 74.5%, whose HBV copies were more than 10(7)/ml accounted
      for 8.3% among the HBeAg-negative patients. The HBV copies of HBeAg-positive
      patients were significantly more than HBeAg-negative patients (P<0.01). The HBV
      copies of anti-HBe-negative patients were significantly more than anti-HBe
      positive patients (P<0.01). The HBV DNA was detected in some HBsAg-negative
      patients. One patient's HBV copies were as high as 1.59 10(9)/ml. CONCLUSIONS:
      The HBV copies of HBeAg-positive patients are significantly more than HBeAg
      negative patients, The HBV copies of anti-HBe-negative patients are significantly
      more than the anti-HBe-positive patients. However, some HBeAg-positive patient's
      HBV copies are very low, and some HBeAg-negative patient's HBV copies are very
      high. HBV DNA even could be detected in some HBsAg-negative patients. It is
      difficult to judge accurately the quantities of HBV and infectivity according to
      the serologic markers for a specific patient.

PMID- 12223137
TI  - [Relationship between hepatitis G virus infection and hepatic failure].
AB  - OBJECTIVE: To study the pathogenic effect of hepatitis G virus (HGV) infection on
      hepatic failure. METHODS: Using the RT-PCR and EIA techniques to detect HGV RNA
      and anti-HGV in sera of hepatic failure patients and compare them with their
      liver function and mortality rates. RESULTS: There was no significant difference
      about the positive rates of HGV among acute hepatic failure, subacute hepatic
      failure and chronic hepatic failure groups (X(2)=2.54, P>0.05). The level of ALT
      in HGV-positive group was slightly lower than that in HGV-negative group. The
      concentration of bilirubin and globulin was higher in HGV-positive group than HGV
      negative group, and the concentration of albumin in HGV-positive group was
      significantly lower than that in HGV-negative group (t=2.59, P<0.05). The
      mortality rate in HGV-positive group was significantly lower than that in HGV
      negative group (X(2)=4.68, 0.01<P<0.05). CONCLUSIONS: The virulence of HGV is
      mild, and the HGV infection does not aggravate hepatic failure.

PMID- 12223138
TI  - [An in vitro model of hepatitis B virus gene replication and expression in
      primary rat hepatocytes transfected with circular viral DNA].
AB  - OBJECTIVE: To establish an in vitro model of hepatitis B virus (HBV) replication
      and expression in primary rat hepatocytes (PRH) transfected with circular viral
      DNA for further study on the interaction of HBV with hepatocytes. METHODS:
      Circular viral DNA containing complete HBV genome were transfected into PRH by
      electroporation (transfected group, about 4mug of circular viral DNA/1
      10(7)cells). From day 1 to day 10 after transfection, HBsAg and HBeAg in the
      supernatants and lysates of PRH were measured with IMX system. HBcAg was assayed
      with western blotting, immunol dot blotting and immunocytochemistry. Meanwhile,
      HBV S-mRNA and X-mRNA were tested with RT-PCR, and replicative intermediates of
      HBV DNA were analyzed by southern blotting and dot blotting. Moreover,
      Transmission electron microscopy was used if viral particles were produced in
      transfected rat hepatocytes. PRH electroporated only was used as control group.
      RESULTS: (1) Viral antigen production in transfected rat hepatocytes: HBsAg in
      cell lysates was positive. P/N values ranged from 4.83 to 85.69, and could be
      maintained for 10 days after transfection. The average P/N values was 18.239
      27.459. Whereas, HBsAg was negative in the supernatants of transfected group (P/N
      values, negative<2.1). HBeAg in the supernatants and lysates of transfected
      hepatocytes all was negative (P/N values<2.1) during 10 days following
      transfection. HBcAg was only found positive in transfected hepatocytes by immunol
      dot blotting. (2) Detection of viral transcripts: transcription of HBV DNA was
      investigated by preparing total RNA from rat hepatocytes 2 days after
      transfection and looking for S-mRNA and X-mRNA by RT-PCR. Results showed S-mRNA
      positive, X-mRNA negative. (3) HBV DNA replication analysis: intracellular total
      DNA was extracted 2 days after transfection and analysed by southern blotting.
      All replicative DNA intermediates, including relaxed circular (rcDNA), covalently
      closed circular (cccDNA), and single-stranded (ssDNA) linear HBV DNA forms, were
      indicated. Dot blotting showed intracellular HBV DNA positive in transfected
      group during 10 days after transfection. However, viral particles were not found
      in transfected hepatocytes during 3 days after transfection. CONCLUSIONS:
      Circular HBV DNA transfected into primary adult rat hepatocytes could obtain
      continuous replication and stable expression of HBV surface antigen. This in
      vitro model has high reproducibility and stability, and is useful for directly
      studying the interaction of HBV with hepatocytes.

PMID- 12223139
TI  - [Effects of different causes on the expression of matrix metalloproteinase 2 in
      hepatic stellate cells].

PMID- 12223140
TI  - [A clinical research on oxymatrine for the treatment of chronic hepatitis B].
AB  - OBJECTIVE: To investigate the clinical effect of oxymatrine on chronic viral
      hepatitis B and to look for new methods for treating hepatitis B. METHODS: Multi
      center, controlled study was used. In this study, 196 patients were allocated to
      oxymatrine, oxymatrine with Ara-AMP, IFN-a1b, and glucose groups to observe ALT,
      AST and viral marker changes. RESULTS: At the end of treatment, the rate of
      normal ALT, the negative rate of HBV DNA and HBeAg, and the positive rate of
      HBeAb were similar in oxymatrine, oxymatrine with Ara-AMP, and IFN-a1b groups. It
      was higher than that of glucose group. After 12 months follow up, the total
      effective rate is 40.8%, 60.8% and 43.1% in oxymatrine, oxymatrine with Ara-AMP,
      and IFN-a1b groups, respectively. CONCLUSIONS: Oxymatrine, oxymatrine with Ara
      AMP, and IFN-a1b are effective to treat hepatitis B with a good negative rate of
      HBV DNA and HBeAg and positive rate of HBeAb.

PMID- 12223141
TI  - [Detection and clinical significance of hepatitis C virus envelope protein 2
      antibody].

PMID- 12223142
TI  - [In vivo inhibition of hepatitis B virus replication and gene expression by
      targeted phosphorothioate modified antisense oligodeoxynucleotides].
AB  - OBJECTIVE: To investigate the antiviral effect of targeted antisense
      oligodeoxynucleotides (asODN) in HBV transgenic mice. METHODS: asODN
      phosphorothioated (5'-CATGCCCCAAAGCCAC-3') targeted to HBV pre-C/C region was
      synthesized. Gal15-PLL was used as drugs carrier which targeted asODN to mice
      liver. Twelve mice with positive serum HBsAg, HBV-DNA were divided into the Gal15
      PLL-asODN-treated group or the control group randomly. In Gal15-PLL- asODN
      treated group, each mouse was injected i.v. asODN 15mug/g weighty/day via tail
      vein for 12 days successively; while in the control group, each mouse received
      the same volume normal saline by the same way. RESULTS: In the Gal15-PLL- asODN
      treated group, serum HBsAg decreased at the 6th day (P<0.05), and decreased
      significantly at the 12th day vs pretreatment (P<0.01). The serum HBV DNA of 4/6
      mice became negative. Immunohistochemistry test showed lowered HBsAg, HBcAg
      content in the liver. In contrast, the control group showed no apparent changes.
      CONCLUSIONS: Gal15-PLL-asODN targeted to pre-C/C region could inhibit HBV
      replication and gene expression.

PMID- 12223143
TI  - [Regulative function of extracelluar regulated protein kinases and telomerase in
      apoptosis of hepatocarcinomatous cell SMMC-7721].
AB  - OBJECTIVE: To study the changes of telomerase activity and protein expression of
      phosphorylated (activated) extracellular regulated protein kinases (ERK1 and
      ERK2) in the course of inhibiting hepatocarcinomatous cell proliferation and
      inducing cell apoptosis by three kinds of chemotherapy drugs: Harringtonine
      (HRT), Vincristine (VCR), and Etoposide (Vp16). To discuss the regulative
      function to hepatocarcinomatous cell apoptosis and interrelation of telomerase
      and ERK. METHODS: Cytotoxicity assay, flow cytometry analysis, telomerase repeat
      amplification protocol assay (TRAP), bioluminescence analysis, and western blot
      were used in this experiment. RESULTS: HRT, VCR, and Vp16 could inhibit cell
      proliferation (0.28% 0.08%, 0.25% 0.16%, 0.24% 0.11%), induce apoptosis (21.12%,
      28.83%, 12.30%), inhibit telomerase activity, and down-regulate the protein
      expression of phosphorylated ERK. CONCLUSIONS: It might be through ERK signal
      transduction pathways that chemotherapy drugs down-regulate telomerase activity
      and induce apoptosis.

PMID- 12223144
TI  - [Ara-Amp and thymus peptide with lamivudine for the treatment of chronic
      hepatitis B].

PMID- 12223145
TI  - [Inhibiting effects of aspirin on the growth of human hepatocellular carcinoma].
AB  - OBJECTIVE: To assess the effects of aspirin on the proliferation and apoptosis of
      human HCC cells. METHODS: The effects of aspirin on the synthesis of DNA in SMMC
      7721 HCC cells were determined by using (3)H-thymidine incorporation. Apoptosis
      of SMMC-7721 was studied by observation of morphologic changes, Tunnel method and
      flow cytometry after treatment with aspirin. We also assessed the effects of
      aspirin on the growth of HCC xenografts in nude mice in vivo. RESULTS: A dose
      dependent suppression (r=-0.918, P<0.01) of (3)H-TdR incorporation in HCC cell
      line treated with aspirin was observed in the concentration range of 1 10(-1)~10(
      7)mol/L. The mean tumor volume and weight in nude mice treated with aspirin were
      significantly lower than those of the control group. The inhibiting rate for HCC
      xenografts was 71.62% in the aspirin group. After exposure to aspirin (31 10(
      3)mol/L) for 48 hours, HCC cells presented some morphologic features of
      apoptosis. The apoptosis index was markedly higher in the aspirin group (8.90%
      1.32%) than in the control group (0.50% 0.35%, P<0.01). A typical subdiploid peak
      before G0/G1 phase with an apoptosis rate as 12.79% was also observed.
      CONCLUSIONS: Aspirin inhibits the proliferation and increases the apoptosis of
      human HCC cells not only in vitro but also in vivo.

PMID- 12223146
TI  - [Action of nitric oxide on testicular dysfunction in cirrhotic rats].
AB  - OBJECTIVE: To investigate the action of nitric oxide (NO) on testicular
      dysfunction in cirrhotic rats. METHODS: Cirrhotic rats were induced by bile duct
      ligation (BDL). Concentration of NO in the serum and homogenates of the
      testicular tissue in biliary cirrhotic rats, L-NAME rats, and sham operated rats
      were measured by assay of nitrate reductase. Concentrations of testosterone in
      the serum of 3 groups were measured by radioimmunoassay. Sperm density and
      percent of motive sperm in the epididymis of the rats were determined. RESULTS:
      Concentrations of NO in the serum and homogenates of the testicular tissue of
      cirrhotic rats were significantly greater than those of sham operated rats (4.165
      micromol/L 1.162 micromol/L, and 1.305 micromol/g 0.087 micromol/g vs 0.535
      micromol/L 0.237 micromol/L and 0.720 micromol/g 0.063 micromol/g).
      Concentrations of testosterone in the serum, the sperm density and percent of
      motive sperm in the epididymis were significantly lower in cirrhotic rats than
      sham operated rats (0.049mug/L 0.020 microgram/L, 16.46% 4.84%, and 86.89
      10(6)/ml 33.17 10(6)/ml vs 2.680 microgram/L 0.403 microgram/L, 62.45% 9.21%, and
      299.43 10(6)/ml 53.85 10(6)/ml). By contrast, the administration of a low dose of
      L-NAME (0.5 mg/kg per day) for one week to cirrhotic rats was associated with a
      significant reduction in concentration of NO (1.975 micromol/L 0.406 micromol/L
      and 0.950 micromol/g 0.057 micromol/g) and a significant increase in
      concentration of testosterone in the serum, the sperm density and percent of
      motive sperm in the epididymis (0.993 microgram/L 0.179 microgram/L, 33.85%
      4.93%, and 188.94 10(6)/ml 38.34 10(6)/ml). CONCLUSIONS: NO is associated with
      testicular dysfunction in cirrhosis. The testicular dysfunction induced by
      cirrhosis can obtain improvement by using low dose of L-NAME.

PMID- 12223147
TI  - [Effect of RAR-beta transfection on the proliferation and phenotype of rat
      hepatic stellate cells].
AB  - OBJECTIVE: To study the effect of RAR-beta transfection plus treatment with the
      corresponding ligand ATRA on the proliferation and phenotype of platelet-derived
      growth factor (PDGF)-activated hepatic stellate cells (HSC). METHODS: PDGF
      activated hepatic stellate cells of rats were transfected with eukaryotic
      expression vector pCMV-script-RAR-beta, which was verified by western blot. The
      proliferation of transfected HSC was assayed by BrdU incorporation as well as MTT
      methods. Their phenotype (alpha-SMA and desmin) was observed by
      immunocytochemistry assay with image analysis and RAR-beta protein expression was
      detected by western blot. RESULTS: Transfection of RAR-beta gene and treatment
      with ligand ATRA could increase the expression of RAR-beta protein for at least
      144h and inhibit the proliferation and the expression of alpha-SMA and desmin in
      PDGF-activated HSC. Significant statistical differences were perceived comparing
      with sham-transfected, only-PDGF treated, non-ligand treated and irrelevant
      ligand-treated HSC. CONCLUSIONS: Transfected with RAR-beta gene as well as using
      related ligand ATRA could suppress the proliferation and reverse the activation
      phenotype of activated HSC.

PMID- 12223148
TI  - [One case of chronic hepatitis B complicated with hemochromatosis].

PMID- 12223149
TI  - [Effects of lamivudine on cirrhotic patients following chronic hepatitis B].

PMID- 12223150
TI  - [Hybrid bioartificial liver for severe hepatitis].

PMID- 12223151
TI  - [Expression of NS5a strong antigenic regions gene of hepatitis C virus in E.coli
      and detection of their antigenicity].

PMID- 12223152
TI  - [Detection of HBV DNA in the liver tissues of the patients with hepatitic
      cirrhosis following hepatitis B with gene chips].

PMID- 12223153
TI  - [Interruption of the transmission of hepatitis B virus from mother to babies].

PMID- 12223154
TI  - [CD81 Present status and prospect of HCV receptor].

PMID- 12223155
TI  - [The expression of sinusoid endothelial cell in warm ischemia in liver from non
      heart-beating donor].

PMID- 12223156
TI  - [Proteome and its application in liver diseases research].

PMID- 12223157
TI  - [Researching progress of prevention and treatment of hepatic failure
      encephalopathy].

PMID- 12223158
TI  - Evaluation of polymerase chain reaction and dot blot hybridisation tests in the
      diagnosis of pigeon circovirus infections.
AB  - Polymerase chain reaction (PCR) and dot blot hybridisation (DBH) tests for
      detecting pigeon circovirus (PiCV) DNA were developed and evaluated using tissue
      samples obtained from diseased and clinically normal pigeons, which originated in
      Belgium and Northern Ireland. When PCR product was visually detected, the limit
      of detection of the PCR test was 31 fg, while that of the DBH was 1.6p g. For
      evaluation purposes, the results of the PCR and DBH tests, performed with DNAs
      extracted from samples of bursa of Fabricius (BF), were compared with those of in
      situ hybridisation (ISH) and histology. In 32 samples tested by all four tests,
      27 (84%) were positive by PCR, 24 (75%) were positive by ISH, 20 (63%) were
      positive by DBH, and 13 (41%) were positive by histology. Additional PCR testing
      showed that in some disease-affected birds, PiCV DNA could be detected in a range
      of tissues including thymus, spleen, liver, kidney and brain. The PCR detection
      of PiCV DNA in BF samples from clinically normal birds indicated that PCR can
      detect infections in the absence of disease, a finding that mitigates against its
      use as a disease diagnostic. In addition, nucleotide sequence determinations
      indicated that PCR test performance was adversely affected by the sequence
      diversity exhibited by selected PiCVs. The application of the DBH test to
      dilutions of test samples indicated that the BF from some diseased pigeons
      contained very large amounts of virus DNA, as much as 10(13)genome copies/g
      tissue, and suggested that this test may be a convenient method of providing a
      semi-quantitative estimate of virus load.

PMID- 12223159
TI  - A reverse transcription-PCR assay to detect viable Mycoplasma synoviae in poultry
      environmental samples.
AB  - In order to study horizontal transmission of Mycoplasma synoviae an avian
      pathogen, a reverse transcription-polymerase chain reaction (RT-PCR) assay was
      developed to detect viable Mycoplasma in environment. The test was based on the
      RT-PCR of the 16S ribosomal RNA (rRNA) of Mycoplasma genus. Results showed that
      Mycoplasma 16S rRNA was stable up to 23 h after cell death. Therefore, the test
      allowed detection of viable or very recently (less than 23 h) dead mycoplasmas.
      M. synoviae survival in artificially contaminated water, food and soil and in the
      environment of M. synoviae experimentally infected turkeys was estimated by
      culture and RT-PCR. The RT-PCR method was then applied in a naturally infected
      laying hen farm showing problems of recurrent mycoplasmosis in the hens. Results
      confirmed the usefulness of RT-PCR in checking the efficiency of biosecurity
      measures and in improving cleaning and disinfection protocols.

PMID- 12223160
TI  - Microbiological comparative study of isolates of Edwardsiella tarda isolated in
      different countries from fish and humans.
AB  - It is difficult to use tissue culture assays to investigate adherence and other
      properties of Edwardsiella tarda because the organism is invasive and produces a
      potent hemolysin. We therefore relied on polymerase chain reaction (PCR) to
      determine the occurrence of genes for enterotoxins (LT-I, EAST-1), Shiga toxin
      (Stx-1, Stx-2), cytotoxic necrotizing factors (CNF-1, CNF-2), aerobactin,
      invasion plasmid of enteroinvasive Escherichia coli, EPEC adherence factor (EAF),
      intimin (Eae), enterohemolysin (EntHly) and hemolysin (Hly) in 53 isolates of E.
      tarda from humans and fish from several countries. All isolates were negative for
      all genes investigated by PCR. Adhesion to and invasion of HeLa cells were
      determined by using the unusually short incubation time of 1h or 30 min. All
      isolates adhered and invaded in these tests. Finally, a random amplified
      polymorphic DNA (RAPD) test distinguished, with a few exceptions, isolates of
      human and fish origin.

PMID- 12223161
TI  - Serobiotypes and virulence genes of Escherichia coli strains isolated from
      diarrheic and healthy rabbits in Brazil.
AB  - A total of 178 Escherichia coli isolates from diarrheic and healthy rabbits in
      the Sao Paulo State (Brazil) were serobiotyped and investigated by PCR for the
      presence of virulence genes. Among the 90 (50.6%) isolates which possessed the
      eae gene, 74 were from diarrheic animals and all but one encoded intimin beta.
      Sixty five (72.2%) of the eae+ isolates had insertion of the locus of enterocyte
      effacement locus in the pheU locus, 11 (12.2%) in the selC and 14 (15.6%) did not
      insert in either of these loci. All isolates were negative for genes of the E.
      coli enterotoxins, Stx1, Stx2, CNF1, CNF2 and EHEC hemolysin. The O132:H2
      serotype was dominant, being present in 63 isolates (70%) of the 90 eae+
      isolates, and 57 of the 63 isolates of this serotype belonged to biotype 30. PCR
      detected the gene for AF/R2 fimbriae in 75 (83.3%) of the 90 eae+ isolates.
      Adherence to HeLa cells was best detected following 6h incubation and a positive
      fluorescence actin staining (FAS) test was given by 52 isolates. These data show
      that isolates of E. coli associated with diarrhea in rabbits in Brazil possess
      the genotype and phenotype typically associated with rabbit enteropathogenic E.
      coli (EPEC). We conclude that EPEC that possess the eae gene are a common cause
      of diarrhea in Brazilian rabbit farms and that the pathogenic eae+ AF/R2+
      isolates of O132:H2:B30 serobiotype are especially predominant.

PMID- 12223162
TI  - The prevalence and PCR detection of Salmonella contamination in raw poultry.
AB  - Contaminated poultry meat has been identified as one of the principal foodborne
      sources of Salmonella. The development of rapid detection assays for Salmonella
      would enable official agencies and food industries to identify contaminated
      foodstuffs in a more timely manner. In addition, these diagnostic tools could
      allow more 'real time' decisions to be made regarding end product acceptability.
      In this study, a survey was carried out to determine the prevalence of Salmonella
      in raw broiler carcasses. A total of 198 neck skin samples were obtained from
      within 40 flocks at a commercial broiler slaughtering facility. The presence of
      Salmonella was assessed by traditional culture methods and by a Salmonella
      specific polymerase chain reaction (PCR) test. Salmonella was recovered from 32
      (16%) of all samples using traditional culture methods. In contrast, the PCR
      assay proved to be more sensitive and detected Salmonella DNA in 38 (19%) of the
      samples tested. The pathogen was detected in 45 (23%) of the 198 samples when
      culture and PCR results were combined. The sensitivity of the PCR test was also
      greater than culture when detecting Salmonella from within flocks (53% of flocks
      by PCR, 30% of flocks by culture). The combination of both tests revealed that
      55% of the flocks were contaminated with Salmonella. The PCR assay proved to be a
      highly specific and sensitive method for detecting Salmonella and the
      incorporation of a routine PCR test in conjunction with standard culture could be
      effective in providing a more accurate profile of the prevalence of this pathogen
      in broiler carcasses.

PMID- 12223163
TI  - Detection of antibodies to Actinobacillus pleuropneumoniae serotype 12 in pig
      serum using a blocking enzyme-linked immunosorbent assay.
AB  - The objective was to develop a blocking enzyme-linked immunosorbent assay (ELISA)
      for detection of antibodies to Actinobacillus pleuropneumoniae (Ap) serotype 12
      in pig serum. Lipopolysaccharide (LPS) from Ap serotype 12 was purified and used
      as antigen in the assay. Antibodies to the LPS antigen in samples of pig serum
      were detected by inhibition of the binding of polyclonal rabbit antibodies raised
      against Ap serotype 12. The assay was evaluated against sera from experimentally
      infected pigs, from pig herds naturally infected with Ap and from herds declared
      free of Ap serotype 12 infection. The blocking ELISA showed no cross-reaction
      when tested with sera from pigs experimentally infected with 12 other serotypes
      of Ap biotype 1. The sensitivity and specificity of the blocking ELISA on the
      herd level was evaluated by testing sera from pig herds naturally infected with
      Ap serotypes 2 and/or 12 and from herds declared free of infection with Ap. The
      Ap serotype 12 blocking ELISA showed a herd sensitivity of 0.77 (95% confidence
      interval, 0.62-0.88) and a herd specificity of 1.00 (0.95-1.00) with a cut-off
      value at 40% relative absorbance or 60% inhibition. The assay may be used
      advantageously as a confirmatory test in serological surveillance programmes for
      Ap infections in SPF systems for pig production.

PMID- 12223164
TI  - Persistence of Escherichia coli O157:H7 in experimentally infected swine.
AB  - These experiments determined the ability of Escherichia coli O157:H7 to colonize
      and persist in pigs simultaneously inoculated with other pathogenic E. coli
      strains. Three-months-old pigs were inoculated with a mixture of five E. coli
      strains. The mixture included two Shiga toxigenic E. coli (STEC) O157:H7 strains,
      two enterotoxigenic E. coli (ETEC) strains and one enteropathogenic E. coli
      (EPEC) strain. A high dose mixture with all five strains at 10(10)CFU/animal
      (CFU: colony forming units) and a low dose mixture with the STEC strains at
      10(7)CFU and the EPEC and ETEC strains remaining at 10(10)CFU were used. The STEC
      strains persisted in the alimentary tracts of some pigs at 2 months post
      inoculation, following inoculation with both the high and low dose mixtures. When
      all strains were given at 10(10)CFU (high dose) the STEC strains persisted in
      greater numbers and in more pigs than did the other E. coli strains. The results
      demonstrated that persistent colonization (> or =2 months) by E. coli O157:H7 can
      occur in pigs. These findings were similar to those reported from sheep
      inoculated with the same mixture of E. coli strains. The results are consistent
      with reports suggesting that pigs have the potential to be reservoir hosts for
      STEC O157:H7.

PMID- 12223165
TI  - Trends in antimicrobial susceptibility in relation to antimicrobial usage and
      presence of resistance genes in Staphylococcus hyicus isolated from exudative
      epidermitis in pigs.
AB  - From 1996 to 2001 a total of 467 Staphylococcus hyicus isolates from exudative
      epidermitis (EE) in pigs in Denmark were examined for susceptibility to 13
      different antimicrobial agents. The presence of selected genes encoding macrolide
      (erm(A), erm(B) and erm(C)), penicillin (blaZ), streptogramin (vat, vga, vga(B),
      vat(B), vat(D) and vat(E)), streptomycin (aadE) and tetracycline resistance
      (tet(K), tet(L), tet(M) and tet(O)) were determined in selected isolates. The
      occurrence of erythromycin resistance increased from 33% in 1996 to a maximum of
      62% in 1997 and decreased to 26% in 2001. Resistance to sulphametazole increased
      from 17% in 1996 to 30% in 1998 but has since decreased to 4% in 2001. Resistance
      to trimethoprim increased to 51% in 1997 and decreased to 21% in 2001. Resistance
      to tetracycline (21-31%) remained relatively constant during 1996-2000, but
      increased to 47% in 2001. Resistance to penicillin (54-75%) streptomycin (33-53%)
      and tetracycline (21-47%) remained relatively constant over the time
      investigated. All 48 penicillin resistant isolates examined contained the blaZ
      gene and 40 (85%) of the streptomycin resistant isolates the aadE gene. It was
      not possible to detect any streptogramin resistance gene in four streptogramin
      resistant isolates. Of the 55 erythromycin resistant isolates examined, five
      contained erm(A), 13 erm(B), 35 erm(C) and two both erm(A) and erm(C). The
      presence of erm(B) was confirmed by hybridization to plasmid profiles in all 13
      PCR-positive isolates. Of 52 tetracycline resistant isolates examined, two
      contained tet(L), 38 tet(K) and 12 both tet(K) and tet(L).

PMID- 12223166
TI  - Amplitude-related characteristics of motor unit and M-wave potentials during
      fatigue. A simulation study using literature data on intracellular potential
      changes found in vitro.
AB  - To realize possible reasons for changes in EMG amplitude characteristics with
      fatigue, we analyzed motor unit potentials (MUPs) and M-waves under simultaneous
      variations of the intracellular action potential (IAP) amplitude, duration, and
      shape as well as of the muscle fiber propagation velocity and desynchronization
      in activation of individual muscle fibers. Analysis was performed through
      computer simulation of MUPs and M-waves detected at different distances from
      active fibers in infinite anisotropic volume conductor. Changes in the IAP spike
      and negative after-potential were taken from in vitro experiments reported in the
      literature. It was shown that the amplitudes of MUP and M-wave detected
      simultaneously at different distances could decrease close to the active fibers,
      be almost unchanged at middle distances, and increase far from the fibers even
      under IAP amplitude decreasing. This reflected the distance-dependent effects of
      changes in the IAP profile along the fiber. Electrode position affected
      sensitivity of MUP and M-wave durations to changes in the IAP duration and
      propagation velocity. Thus, the signal area and RMS depended on electrode
      position and could change with fatigue in a way different from that of signal
      amplitude. The results can help to avoid misleading interpretation of EMG
      changes.

PMID- 12223167
TI  - The differential effects of fatigue on reflex response timing and amplitude in
      males and females.
AB  - We examined the effects of fatigue on patellar tendon reflex responses in males
      and females. A spring-loaded reflex hammer elicited a standardized tendon tap
      with the knee positioned in an isokinetic dynamometer and flexed to 85 degrees.
      We recorded vastus lateralis activity (SEMG) and knee extension force production
      at the distal tibia (force transducer). Reflex trials were performed before and
      after (immediate, 2, 4, and 6 min) an isokinetic fatigue protocol to 50% MVC (90
      degrees /s). For each event, pre-motor time (PMT), electromechanical delay (EMD),
      and total motor time (TMT) were obtained, as well as EMG amplitude (EMG(amp)),
      time to peak EMG (EMG(tpk)), peak force amplitude (F(amp)), time to peak force
      (F(tpk)), EMG:force ratio (E:F), and rate of force production (F(rate)=N/ms). TMT
      increased significantly in females following fatigue, while males showed no
      change. The increased TMT was due to an increased EMD with fatigue, while PMT was
      unaffected. EMG(amp) and F(amp) were somewhat diminished in females yet
      significantly augmented in males following fatigue, likely accounting for the
      differential changes in EMD noted. Results suggest males and females may respond
      differently to isokinetic fatigue, with males having a greater capacity to
      compensate for contraction force failure when responding to mechanical
      perturbations.

PMID- 12223169
TI  - Soleus H-reflex dynamics during fast plantarflexion in humans.
AB  - The relationship between the size of the soleus (Sol) Hoffmann (H-) reflex and
      the level of background (BG) electromyographic (EMG) activity was examined during
      plantarflexing at different force levels. The experiments were carried out on
      seven healthy male subjects aged 20-37 years. The subjects were asked to perform
      fast plantarflexion under a reaction-time condition. The amounts of contraction
      force were 10, 20, 50 and 80% of maximum voluntary contraction (MVC). Since the
      maximum size of the M-wave (Mmax) changed systematically during the
      plantarflexion, we tried to maintain the size of the reference M-wave, an
      indicator of the efficiency of the electrical stimulation, at a constant value
      (20% of Mmax) throughout the experiment. The size of the H-reflex was rapidly
      increased at the very beginning of the movement, and then it tended to decrease
      in the later phase of the movement. Consequently, even with the same level of BG
      EMG, the size of the H-reflex was always larger in the early rising phase of the
      EMG activity than in the later falling phase. The maximum size of the H-reflex
      was poorly correlated with the force exerted. In contrast, the size of the F
      response was proportional to the force exerted. The non-linear relationship
      between the size of the H-reflex and the BG EMG suggests that the level of the
      presynaptic inhibition onto Ia terminals was modified depending on the required
      force level and during the course of the movement.

PMID- 12223168
TI  - Assessment of soleus motoneuronal excitability using the joint angle dependent H
      reflex in humans.
AB  - As variations in the amplitude of H reflex potentials can be influenced by
      changes in muscle length, motoneuronal excitability in terms of H reflex during
      free movement has long been argued. With the maximal M response controlled, the
      present study compared several H reflex parameters in order to assess
      motoneuronal excitability of the resting soleus for different ankle angles
      (plantarflexion 20 degrees, neutral, and dorsiflexion 20 degrees ). All H-related
      parameters were dependent on joint angle, suggesting that soleus motoneuronal
      excitability in the dorsiflexed position was significantly suppressed. By
      contrast, soleus motoneuronal excitability in the plantarflexed position was not
      effectively modulated since H-related parameters did not differ from their
      neutral-position analogs. Methodologically, assessment of joint angle-dependent
      modulation of motoneuronal excitability requires meticulous control of M
      responses and selection of appropriate parameters that are insensitive to
      possible physical modulation and spatial shift of the M recruitment curve
      confounded by geometrical factors.

PMID- 12223170
TI  - Agonist-antagonist common drive during fatiguing knee extension efforts using
      surface electromyography.
AB  - AIM: This study examined the electromyographic (EMG) activity of knee extensor
      agonists and a knee extensor antagonist muscle during fatiguing isometric
      extensions across a range of force levels. METHODS: Five female subjects
      performed isometric knee extensions at 25%, 50%, 75% and 100% of their maximal
      voluntary contraction (MVC) with the knee flexed to 75 degrees. Surface EMG
      (SEMG) was recorded with bipolar electrodes from the vastus lateralis (VL),
      vastus medialis (VM), rectus femoris (RF) and biceps femoris (BF) and the root
      mean-squared (RMS) amplitude and the percentage frequency compression of these
      recordings were calculated. Commonality and cross talk between recordings were
      also examined. RESULTS: Cross talk between recordings was deemed negligible
      despite significant levels of commonality between the agonist and antagonist
      SEMG, which was attributed to common drive. SEMG RMS amplitude increased
      significantly for all muscles during the 25%, 50%, 75% MVC knee extensions until
      task failure, and decreased significantly for 100% MVC. The frequency spectrum of
      the SEMG compressed significantly for all muscles and % MVC levels. The VM, VL
      and BF SEMG recordings responded similarly to fatigue. The RF's frequency
      spectrum compressed to a significantly higher degree. CONCLUSIONS: The VM, VL,
      RF, and BF fatigue in parallel, with high similarity between VM, VL and BF,
      giving support to the concept of a shared agonist-antagonist motoneuron pool.

PMID- 12223171
TI  - The function of gastrocnemius as a knee flexor at selected knee and ankle angles.
AB  - The gastrocnemius has been viewed as an important contributor at the knee joint
      as a joint flexor and stabilizer across all the knee and ankle joint angles. The
      purpose of this study was to investigate the influence of knee and ankle joint
      angles on the knee flexor function of the gastrocnemius. Seventeen participants
      were tested on a Biodex dynamometer with the gastrocnemius muscle selectively
      stimulated at a standardized level of electrical current. The results indicated
      that both ankle and knee joint angle influence the knee joint flexion moment
      produced by the gastrocnemius. Further analysis revealed that the flexion moment
      was greatest with the knee joint straight (180 degrees ) across all ankle joint
      angles. The greatest reduction in knee flexion moment occurred between 180 and
      165 degrees of knee angle. No significant difference was observed in the knee
      flexion moment between 165 degrees and 115 degrees knee flexion, and little knee
      flexion moment was observed at knee angles of 90 degrees and 75 degrees. The
      dramatic reduction of moment between 180 degrees and 165 degrees knee angle is
      possibly due to the change of moment arm while the little moment production
      during extreme flexion (90 degrees and 75 degrees ) may be due to the reduction
      of muscle length.

PMID- 12223172
TI  - Effect of PNF stretch techniques on knee flexor muscle EMG activity in older
      adults.
AB  - The effects of proprioceptive neuromuscular facilitation (PNF) stretch techniques
      on older adults are unknown and the physiological changes associated with aging
      may lead to differential responses to PNF stretching. Therefore, the purpose of
      this experiment was to examine the effects of PNF stretch techniques and EMG
      activity in older adults. Three PNF stretch techniques: static stretch (SS),
      contract-relax (CR), and agonist contract-relax (ACR) were applied to 24 older
      adults aged 50-75 years. The subjects were tested for knee extension range of
      motion (ROM) and knee flexor muscle EMG activity. The results indicated that ACR
      produced 29-34% more ROM and 65-119% more EMG activity than CR and SS,
      respectively. It was concluded that PNF stretch techniques can increase ROM in
      older adults. However, a paradoxical effect was observed in that PNF stretching
      may not induce muscular relaxation even though ROM about a joint increases. Care
      should be taken when applying PNF stretch techniques to older adults due to age
      related alterations in muscle elasticity.

PMID- 12223173
TI  - EMG-angle relationship of the hamstring muscles during maximum knee flexion.
AB  - The aim of the present study was to investigate the EMG-joint angle relationship
      during voluntary contraction with maximum effort and the differences in activity
      among three hamstring muscles during knee flexion. Ten healthy subjects performed
      maximum voluntary isometric and isokinetic knee flexion. The isometric tests were
      performed for 5 s at knee angles of 60 and 90 degrees. The isokinetic test, which
      consisted of knee flexion from 0 to 120 degrees in the prone position, was
      performed at an angular velocity of 30 degrees /s (0.523 rad/s). The knee flexion
      torque was measured using a KIN-COM isokinetic dynamometer. The individual EMG
      activity of the hamstrings, i.e. the semitendinosus, semimembranosus, long head
      of the biceps femoris and short head of the biceps femoris muscles, was detected
      using a bipolar fine wire electrode. With isometric testing, the knee flexion
      torque at 60 degrees knee flexion was greater than that at 90 degrees. The mean
      peak isokinetic torque occurred from 15 to 30 degrees knee flexion angle and then
      the torque decreased as the knee angle increased (p<0.01). The EMG activity of
      the hamstring muscles varied with the change in knee flexion angle except for the
      short head of the biceps femoris muscle under isometric condition. With isometric
      contraction, the integrated EMGs of the semitendinosus and semimembranosus
      muscles at a knee flexion angle of 60 degrees were significantly lower than that
      at 90 degrees. During maximum isokinetic contraction, the integrated EMGs of the
      semitendinosus, semimembranosus and short head of the biceps femoris muscles
      increased significantly as the knee angle increased from 0 to 105 degrees of knee
      flexion (p<0.05). On the other hand, the integrated EMG of the long head of the
      biceps femoris muscle at a knee angle of 60 degrees was significantly greater
      than that at 90 degrees knee flexion with isometric testing (p<0.01). During
      maximum isokinetic contraction, the integrated EMG was the greatest at a knee
      angle between 15 and 30 degrees, and then significantly decreased as the knee
      angle increased from 30 to 120 degrees (p<0.01). These results demonstrate that
      the EMG activity of hamstring muscles during maximum isometric and isokinetic
      knee flexion varies with change in muscle length or joint angle, and that the
      activity of the long head of the biceps femoris muscle differs considerably from
      the other three heads of hamstrings.

PMID- 12223174
TI  - Changes in kinematic and EMG variability while practicing a maximal performance
      task.
AB  - This paper examines changes in the variability of electromyographic (EMG)
      activity and kinematics as a result of practicing a maximal performance task.
      Eight subjects performed rapid elbow flexion to a target in the horizontal plane.
      Four hundred trials were distributed equally over four practice sessions. A
      potentiometer at the elbow axis of rotation of a manipulandum recorded the
      angular displacement. The EMG activity of the biceps and the triceps brachii was
      monitored using Beckman surface electrodes. Limb speed increased while both
      target error and trajectory (velocity versus position) variability decreased.
      There was an increase in the absolute measure of total EMG variability (the first
      standard deviation at each point of the biceps and triceps waveform multiplied
      together). However, the coefficient of variation (the first standard deviation
      divided by the mean and the result multiplied by 100) of the mean amplitude value
      of the individual EMG bursts decreased. The variability of triceps motor time
      also decreased while the variability biceps motor time remained unchanged. The
      results demonstrated a clear relationship between kinematic and EMG variability.
      The EMG and the trajectory data suggest that practice resulted in greater central
      nervous system control over both the spatial-temporal aspects of movement and the
      magnitude of the biceps and triceps muscle force-impulses.

PMID- 12223175
TI  - Comparison of measurement accuracy between two wrist goniometer systems during
      pronation and supination.
AB  - Pronation and supination have been shown to affect wrist goniometer measurement
      accuracy. The purpose of this study was to compare differences in measurement
      accuracy between a commonly used biaxial, single transducer wrist goniometer
      (System A) and a biaxial, two-transducer wrist goniometer (System B) over a wide
      range of pronation and supination (P/S) positions. Eight subjects moved their
      wrist between -40 and 40 degrees of flexion/extension (F/E) and -10 and 20
      degrees of radial/ulnar (R/U) deviation in four different P/S positions: 90
      degrees pronation; 45 degrees pronation; 0 degrees neutral and 45 degrees
      supination. System A was prone to more R/U crosstalk than System B and the amount
      of crosstalk was dependent on the P/S position. F/E crosstalk was present with
      both goniometer systems and was also shown to be dependent on P/S. When moving
      from pronation to supination, both systems experienced a similar extension offset
      error; however R/U offset errors were roughly equal in magnitude but opposite in
      direction. The calibration position will affect wrist angle measurements and the
      magnitude and direction of measurement errors. To minimize offset errors, the
      goniometer systems should be calibrated in the P/S posture most likely to be
      encountered during measurement. Differences in goniometer design and application
      accounted for the performance differences.

PMID- 12223176
TI  - Nebivolol: a selective beta(1)-adrenergic receptor antagonist that relaxes
      vascular smooth muscle by nitric oxide- and cyclic GMP-dependent mechanisms.
AB  - Nebivolol is a highly selective beta(1)-adrenergic receptor antagonist that also
      possesses vasodilator properties that are attributed largely to nitric oxide
      (NO). The objective of the present study was to elucidate in more detail the
      mechanisms by which nebivolol relaxes vascular smooth muscle. In the canine
      species, nebivolol caused relaxation of isolated precontracted rings of coronary
      artery and pulmonary artery largely by endothelium-dependent, NO-dependent, and
      cyclic GMP-dependent mechanisms. Vasorelaxation was inhibited by N(G)
      methylarginine, and this inhibition was reversed by addition of excess L
      arginine. Moreover, the vasorelaxant responses to nebivolol were markedly
      inhibited by oxyhemoglobin, methylene blue, and 1H-[1,2,4]oxadiazolo[4,3
      alpha]quinoxalin-1-one (ODQ), whereas vasorelaxation was enhanced by zaprinast.
      Rat aortic ring preparations, however, relaxed in response to nebivolol by both
      endothelium-dependent and endothelium-independent mechanisms, both involving NO,
      and cyclic GMP. Endothelium-dependent and endothelium-independent vasorelaxation
      were inhibited by oxyhemoglobin, methylene blue, and ODQ. However, only
      endothelium-dependent vasorelaxation in response to nebivolol was inhibited by
      N(G)-methylarginine. Additional experiments ruled out other endothelium
      independent vasorelaxant mechanisms. In conclusion, the vasodilator responses to
      nebivolol involve NO and cyclic GMP in both vascular endothelial and smooth
      muscle cells.

PMID- 12223177
TI  - Nebivolol inhibits vascular smooth muscle cell proliferation by mechanisms
      involving nitric oxide but not cyclic GMP.
AB  - The objective of this study was to elucidate the mechanisms by which nebivolol, a
      cardio-selective beta-adrenergic receptor antagonist, inhibits rat aortic smooth
      muscle cell (RASMC) proliferation. Nebivolol was compared with DETA-NO and S
      nitroso-N-acetylpenicillamine (SNAP), two nitric oxide (NO) donor agents, and
      alpha-difluoromethylornithine (DFMO), a known inhibitor of ornithine
      decarboxylase (ODC). All four test agents inhibited RASMC proliferation in a
      concentration-dependent manner, with nebivolol being the most potent (IC(50) =
      4.5 microM), whereas atenolol, another relatively selective beta(1)-blocker, was
      inactive. DFMO, nebivolol, and DETA-NO interfered with cell proliferation in a
      cell-density-dependent manner, the lower the cell density the greater the
      inhibition of cell proliferation. The cytostatic effects of nebivolol and DETA-NO
      were completely independent of cyclic GMP, as neither ODQ (cytosolic guanylyl
      cyclase inhibitor) nor zaprinast (cyclic GMP phosphodiesterase inhibitor)
      affected the antiproliferative action of nebivolol or DETA-NO. The cytostatic
      effects of nebivolol, SNAP, and DFMO were largely prevented by the addition of
      excess putrescine, but not ornithine, to cell cultures. Moreover, nebivolol
      caused a marked reduction in the intracellular levels of putrescine, spermidine,
      and spermine. Like DFMO, nebivolol and DETA-NO interfered with the G(1)-phase to
      S-phase cell cycle transition in RASMC. These observations confirm previous
      findings that DFMO and NO interfere with RASMC proliferation by inhibiting ODC
      and polyamine production and provide evidence that nebivolol works by the same
      mechanism.

PMID- 12223178
TI  - Differential expression and localization of nitric oxide synthases in cirrhotic
      livers of bile duct-ligated rats.
AB  - Increased vascular nitric oxide (NO) production has been implicated in the
      pathogenesis of the hyperdynamic circulation in liver cirrhosis. This study
      investigated the expression of three isoforms of NO synthase (NOS) in rat
      cirrhotic livers. Cirrhosis was induced by chronic bile duct ligation (BDL). NOS
      enzyme activity was assessed by L-citrulline generation. Competitive RT-PCR was
      performed to detect the mRNA levels of NOS. In situ hybridization was done to
      localize NOS mRNA. Protein expression of NOS was evaluated by Western blotting
      and immunohistochemistry. The L-citrulline assay showed that constitutive NOS
      (cNOS) enzymatic activity was decreased, while inducible NOS (iNOS) activity was
      increased in BDL livers. Both endothelial NOS (eNOS) and neuronal NOS (nNOS) mRNA
      were detected in BDL and sham rats, but with enhanced expression in BDL rats.
      eNOS protein was redistributed with less expression in sinusoidal endothelial
      cells, but the total levels in liver were not changed. nNOS was induced in
      hepatocytes of BDL rats, in contrast to only a weak signal observed around some
      blood vessels in sham livers. Intense mRNA and protein expression of iNOS was
      induced in livers of BDL rats and was localized in hepatocytes, with no or a
      negligible amount in control livers. In conclusion, iNOS was induced in cirrhotic
      liver with its activity increased. In contrast, cNOS activity was impaired,
      regardless of unchanged eNOS protein levels and enhanced nNOS expression. These
      results suggest that all three types of NOS have a role in cirrhosis, but their
      expression and regulation are different.

PMID- 12223179
TI  - Mechanistic insight into exclusive nitric oxide recovery from a carbon-bound
      diazeniumdiolate.
AB  - We report that NaON=N(O)-X-N(O)=NONa (1), where X is para-disubstituted benzene,
      hydrolyzes to 2 mol of nitric oxide (NO) with concurrent production of 1 mol of p
      benzoquinone dioxime at physiological pH. The reaction is acid catalyzed, with a
      rate that slows as the substrate concentration is increased. The results
      demonstrate that a carbon-bound diazeniumdiolate can be quantitatively hydrolyzed
      to produce NO as the only gaseous nitrogen-containing product. The data also
      suggest that N-N bond cleavage is the rate-determining step in NO release, since
      C-N cleavage followed by dissociation of O=N-N=O to two NO molecules cannot be
      operative in this case. The finding that this oxime can absorb NO in organic
      media and regenerate it quantitatively at physiological pHs extends the potential
      pharmacological implications of the carbon-bound diazeniumdiolates.

PMID- 12223180
TI  - Abrogation of bleomycin-induced lung fibrosis by nitric oxide synthase inhibitor,
      aminoguanidine in mice.
AB  - The effects of aminoguanidine (AG), a specific inhibitor of inducible nitric
      oxide synthase, on the bleomycin (BL)-induced lung fibrosis was evaluated in
      mice. The animals were placed into five groups: saline (SA)-instilled drinking
      water (SA+H(2)O), saline-instilled drinking water containing 0.5%AG (SA+0.5%AG),
      BL-instilled drinking water (BL+H(2)O), BL-instilled drinking water containing
      0.2%AG (BL+0.2%AG), and BL-instilled drinking water containing 0.5%AG
      (BL+0.5%AG). The mice had free access to H(2)O or H(2)O containing AG and lab
      chow ad lib 2 days prior to intratracheal (IT) instillation of BL
      (0.07U/mouse/100 microL) or an equivalent volume of sterile isotonic saline. The
      mice in the SA+0.5%AG group consumed the greatest amount of AG without any ill
      effects than the mice in any other group. There were no differences in any of the
      measured biochemical determinants between the SA+H(2)O and SA+0.5%AG control
      groups. The IT instillation of BL in the BL+H(2)O group caused significant
      increases in the lipid peroxidation, hydroxyproline content, and prolyl
      hydroxylase activity of lungs and influx of inflammatory cells in the
      broncheoalveolar lavage fluid (BALF) as compared to both control groups. The
      intake of aminoguanidine by mice in the BL+0.5%AG group caused significant
      reductions in the BL-induced increases in all measured biochemical indices of
      lung fibrosis without any effects on the influx of inflammatory cells in the
      BALF. In fact, AG in both BL-treated groups additionally increased the total cell
      counts in the BALF from mice in the BL+0.2%AG and BL+0.5%AG groups as compared to
      the BL+H(2)O group. Histopathological evaluation of the lungs revealed that the
      mice in the BL+0.5%AG group had markedly fewer fibrotic lesions than mice in the
      BL+H(2)O group. These results demonstrate that aminoguanidine minimizes the BL
      induced lung fibrosis at both the biochemical and the morphological level and
      support our earlier hypothesis that the production of nitric oxide plays a
      significant role in the pathogenesis lung fibrosis caused by BL.

PMID- 12223181
TI  - NO synthesis and its regulation in the arachidonic-acid-stimulated rat
      polymorphonuclear leukocytes.
AB  - Nitric oxide (NO) synthesis and free radical generation from polymorphonuclear
      leukocytes (PMNs) play an important role in several pathological conditions. In
      the present study, regulation of NO synthesis has been investigated in the
      unstimulated and arachidonic-acid (AA)-stimulated rat PMNs. L-Citrulline
      formation or nitrite content was used as a marker of NO synthesis, while AA
      induced free radical generation was assessed by flow cytometry using a dye,
      2('),7(')-dichlorofluoreseindiacetate. L-Citrulline formation in the unstimulated
      PMNs increased in a time-dependent manner for up to 120 min. The increase was
      significantly less (25-55%) in AA-stimulated PMNs at all the time points. AA
      induced free radical generation was maximum during the first 15 min followed by a
      time-dependent decrease. Interestingly, similar experiments under hyperoxic
      conditions did not exhibit any decrease in L-citrulline and nitrite formation
      after AA stimulation even though the free radical generation further increased.
      Scavenging or inhibition of free radicals by several types of interventions
      increased NO generation from AA-stimulated PMNs. The results of the present study
      suggest that the availability of oxygen, a common substrate for both NADPH
      oxidase and NOS, can inversely affect the synthesis of NO and PMNs seem to prefer
      oxygen utilization over NO synthesis for free radical generation.

PMID- 12223182
TI  - Application of the nitric oxide donor SNAP to cardiomyocytes in culture provides
      protection against oxidative stress.
AB  - Multiple data indicates that nitric oxide (NO) donors retain immediate protective
      effects against different disturbances in cardiovascular system. The aim of the
      present study was to investigate delayed effects of nitric oxide donor S-nitroso
      N-acetyl-l,l-penicillamine (SNAP) application in cardiac H9c2 cell line.
      Cardiomyocytes were treated with SNAP for 2h followed by 24h wash with fresh
      growth medium. The concentration curve was constructed in range from 0.5 to 2mM,
      toxicity was observed at 2mM concentration of SNAP. For the study of SNAP-induced
      protection against t-butyl hydroperoxide-induced oxidative injury 1mM
      concentration was used. Cell viability was assessed by MTT reductase activity
      assay; mitochondrial transmembrane potential (mdeltapsi) was measured by flow
      cytometry with fluorescent dye DiOC(6). Synthesis of heat-shock proteins (hsps)
      was analyzed by Western blot. Analysis of the cell viability and mdeltapsi
      reflected delayed protective effect of 1mM SNAP application against oxidative
      injury. SNAP in 1mM concentration caused 70% induction of hsp75 synthesis in
      cardiomyocytes. However, the other analyzed hsps (hsp70, hsp27, hsp60, hsp10, and
      CyP A) did not display any significant induction after incubation with SNAP.
      Present work demonstrates that the NO donor SNAP causes delayed protection
      against oxidative stress in H9c2 cardiomyocyte cell line, reflected in cell
      viability increase and preservation of the mdeltapsi. We suppose the major
      pathway for the development of SNAP-induced protection is through mitochondria.
      Induction of hsp75 expression following SNAP pretreatment is one possible way to
      explanation the mechanisms of this protection.

PMID- 12223183
TI  - Physiological mechanisms regulating the expression of endothelial-type NO
      synthase.
AB  - Although endothelial nitric oxide synthase (eNOS) is a constitutively expressed
      enzyme, its expression is regulated by a number of biophysical, biochemical, and
      hormonal stimuli, both under physiological conditions and in pathology. This
      review summarizes the recent findings in this field. Shear stress, growth factors
      (such as transforming growth factor-beta, fibroblast growth factor, vascular
      endothelial growth factor, and platelet-derived growth factor), hormones (such as
      estrogens, insulin, angiotensin II, and endothelin 1), and other compounds (such
      as lysophosphatidylcholine) upregulate eNOS expression. On the other hand, the
      cytokine tumor necrosis factor-alpha and bacterial lipopolysaccharide
      downregulate the expression of this enzyme. The growth status of cells, the actin
      cytoskeleton, and NO itself are also important regulators of eNOS expression.
      Both transcriptional and posttranscriptional mechanisms are involved in the
      expressional regulation of eNOS. Different signaling pathways are involved in the
      regulation of eNOS promoter activity and eNOS mRNA stability. Changes in eNOS
      expression and activity under pathophysiological conditions and the
      pharmacological modulation of eNOS expression are subject of a subsequent brief
      review (part 2) to be published in the next issue of this journal.

PMID- 12223184
TI  - Inheritance and mapping of 11 avirulence genes in Phytophthora sojae.
AB  - Two new crosses involving four races (races 7, 16, 17, and 25) of the soybean
      root and stem rot pathogen Phytophthora sojae were established (7/16 cross; 17/25
      cross). An F2 population derived from each cross was used to determine the
      genetic basis of avirulence towards 11 different resistance genes in soybean.
      Avirulence was found to be dominant and determined by a single locus for Avr1b,
      1d, 1k, 3b, 4, and 6, as expected for a simple gene-for-gene model. We also
      observed several cases of segregation, inconsistent with a single dominant gene
      being solely responsible for avirulence, which suggests that the genetic
      background of the different crosses can affect avirulence. Avr4 and 6
      cosegregated in both the 7/16 and 17/25 crosses and, in the 7/16 cross, Avr1b and
      1k were closely linked. Information from segregating RAPD, RFLP, and AFLP markers
      screened on F2 progeny from the two new crosses and two crosses described
      previously (a total of 212 F2 individuals, 53 from each cross) were used to
      construct an integrated genetic linkage map of P. sojae. This revised genetic
      linkage map consists of 386 markers comprising 35 RFLP, 236 RAPD, and 105 AFLP
      markers, as well as 10 avirulence genes. The map is composed of 21 major linkage
      groups and seven minor linkage groups covering a total map distance of 1640.4cM.

PMID- 12223185
TI  - Differential expression of desaturases and changes in fatty acid composition
      during sporangiospore germination and development in Mucor rouxii.
AB  - Polyunsaturated fatty acids (PUFAs), namely, oleic (C18:1), linoleic (C18:2), and
      gamma-linolenic acid (C18:3), constituted the majority in the total fatty acid
      content (44%) of sporangiospores of Mucor rouxii. At 30 degrees C, the
      germination begins within 1h at which time spore swelling occurs, followed by
      germ tube emergence within 3-4h. Throughout germination, an increase in gamma
      linolenic acid (GLA) was observed and its content was highest at germ tube
      emergence. It took longer for sporangiospores of M. rouxii to germinate at sub
      optimal temperatures (15 and 35 degrees C). However, the content of GLA was
      higher at the germ tube initiation than at the mycelial stage at all
      temperatures, suggesting the association of GLA and germination of
      sporangiospores. This finding was substantially confirmed by differential
      expression of delta9-, delta12-, and delta6-desaturase genes measured during
      spore germination. The expression of three desaturase genes parallels the pattern
      of GLA synthesis. By using RT-PCR techniques to follow gene expression, we found
      that mRNA of delta12- and delta6-desaturase genes were translated as soon as the
      spores were introduced into a fresh medium while the mRNA of delta9-desaturase
      gene could not be detected until 2h after introduction. A sharp increase in mRNA
      of delta6-desaturase genes correlated well with an increase in GLA content at
      germ tube emergence (4h). These results demonstrated that changes in fatty acid
      composition of sporangiospore of M. rouxii and differential expression of
      desaturase genes occurred during germination, and that extensive changes in GLA
      synthesis associated with some events in germination process.

PMID- 12223186
TI  - Physical mapping of plasmid and cosmid clones in filamentous fungi by fiber-FISH.
AB  - Fluorescence in situ hybridization to extended DNA fibers (fiber-FISH) serves as
      a powerful tool for direct physical mapping in plants and animals. Here, we show
      that fiber-FISH is useful for contig mapping as well as for estimating the
      physical distance between genetic markers in fungi. A five-cosmid contig from a
      chromosome of Nectria haematococca and four cloned genetic markers from a linkage
      map of Cochliobolus heterostrophus were chosen as models for the application of
      this technology. In N. haematococca, overlapping and non-overlapping clones were
      visually mapped on individual DNA fibers, confirming the results from
      conventional physical mapping perfectly. Fiber-FISH concomitantly indicated the
      gap size or the extent of overlap between two clones. In C. heterostrophus, the
      physical distance between the two pairs of genetic markers could be estimated
      from the microscopic measurements of the intervals. Chromosomal DNA isolated from
      a pulsed field gel was suitable for preparing the DNA fibers.

PMID- 12223187
TI  - Visualization of vacuoles in Aspergillus oryzae by expression of CPY-EGFP.
AB  - Vacuolar carboxypeptidase Y (CPY) from Aspergillus nidulans was used to construct
      a CPY-EGFP fusion protein and expressed in A. oryzae to study vacuolar morphology
      and functions in A. oryzae. While the fluorescence of EGFP was barely detectable
      in A. oryzae expressing CPY-EGFP grown under normal conditions at pH 5-6, the
      increase in pH of the growth medium towards alkalinity restored the fluorescence.
      In accordance with such an observation, the fluorescence of CPY-EGFP fusion
      protein in cell extract decreased in acidic pH condition, concomitant with
      lowered content of EGFP detected in A. oryzae grown under acidic pH conditions.
      The pH sensitivity of EGFP fluorescence and enhanced degradation of proteins in
      vacuoles under acidic pH conditions are thus proposed to result in the reduction
      of fluorescence in A. oryzae. Further, visualization of vacuoles revealed the
      presence of peculiar ring- or tube-like structures as distinct from normal
      spherical-shaped vacuoles.

PMID- 12223188
TI  - Expression of a Pho85 cyclin-dependent kinase is repressed during the dimorphic
      transition in Sporothrix schenckii.
AB  - Sporothrix schenckii is a pathogenic fungus that undergoes a dimorphic transition
      from yeast to mycelium in response to environmental conditions such as cell
      density, temperature, and calcium. We identified a homolog of the Pho85 cyclin
      dependent kinase (Cdk) that mediates cellular responses to environmental
      conditions in other organisms. By Western blot, three proteins containing the
      PSTAIRE motif, which characterize the cyclin-dependent protein kinases, were
      identified in S. schenckii. The gene encoding a Pho85 homolog, PhoSs, was
      identified and sequenced. The phoSs gene consists of 990bp, contains one intron,
      and encodes a protein of 306 amino acids. The S. schenckii Pho85 homolog shares
      features with Cdks, including the PSTAIRE motif, an ATP binding domain, and a
      serine-threonine kinase domain. By quantitative competitive RT-PCR, expression of
      the phoSs gene was found to decrease 30-fold during the yeast to mycelium
      transition. The addition of extracellular calcium accelerated the dimorphic
      transition and restored phoSs expression. These findings suggest PhoSs may
      participate in the control of the yeast to mycelium transition in S. schenckii.

PMID- 12223189
TI  - delta-(L-alpha-Aminoadipyl)-L-cysteinyl-D-valine synthetase, that mediates the
      first committed step in penicillin biosynthesis, is a cytosolic enzyme.
AB  - Penicillin biosynthesis by Penicillium chrysogenum is a compartmentalized
      process. The first catalytic step is mediated by delta-(L-alpha-aminoadipyl)-L
      cysteinyl-D-valine synthetase (ACV synthetase), a high molecular mass enzyme that
      condenses the amino acids L-alpha-aminoadipate, L-cysteine, and L-valine into the
      tripeptide ACV. ACV synthetase has previously been localized to the vacuole where
      it is thought to utilize amino acids from the vacuolar pools. We localized ACV
      synthetase by subcellular fractionation and immuno-electron microscopy under
      conditions that prevented proteolysis and found it to co-localize with
      isopenicillin N synthetase in the cytosol, while acyltransferase localizes in
      microbodies. These data imply that the key enzymatic steps in penicillin
      biosynthesis are confined to only two compartments, i.e., the cytosol and
      microbody.

PMID- 12223190
TI  - Improving the efficiency of gene replacements in Neurospora crassa: a first step
      towards a large-scale functional genomics project.
AB  - Here, we report the use of the mating type heterokaryon incompatibility system as
      a counterselection to increase the probability of identifying gene replacements
      in Neurospora crassa. We compared the frequencies of gene replacements observed
      among transformants obtained by using plasmids with or without the mat a-1(+)
      gene (hereby called "Toxic Gene") placed adjacent to disruption cassettes. On an
      average, we were 20x more likely to identify a correct gene replacement by
      incorporating the toxic gene in our constructs. Using this strategy, we
      constructed strains containing a deletion of the inl (1L-myo-inositol-1-phosphate
      synthase) gene. Finally, we demonstrated that we were able to remove the
      transformation marker (the hygromycin B phosphotransferase- thymidine kinase gene
      fusion [hph(+)::tk(+)]) from the genome by using a strategy similar to the "URA
      blaster" strategy used in yeast, which we call "tk-blaster."

PMID- 12223191
TI  - The veA gene activates sexual development in Aspergillus nidulans.
AB  - The previously isolated gene complementing the veA1 mutation was confirmed to be
      the veA gene. The determined nucleotide sequence of the gene demonstrated that
      there is an open reading frame (ORF) of a 573 amino acid polypeptide. The
      nucleotide sequence matched some clones of which functions were not assigned yet
      and the amino acid sequence matched that of Neurospora crassa VeA-related protein
      with 61% similarity. The nucleotide sequence of the veA1 mutant gene differed
      from that of the wild type gene by only one nucleotide and the nucleotide G in
      the initiation codon ATG of the VeA ORF was mutated to the nucleotide T. Then,
      the mutant ORF may use the 37th methionine codon of the wild type one as a new
      initiation codon. The veA transcript was present in the conidia and in mycelia
      cultured for up to 14h and expressed almost constitutively at an increased level
      throughout the asexual and sexual developmental processes, suggesting that it may
      act from a relatively early developmental stage. Null mutants of the gene never
      formed sexual structures, even under conditions where sexual development
      preferentially occurs in wild types. Over-expressors of the gene formed larger
      numbers of sexual structures with a much reduced number of conidial heads than a
      control strain (a veA1 mutant), even under conditions where wild type strains
      form little sexual structure but form conidial heads very well, such as in the
      presence of a salt at high concentration. Furthermore, over-expressors could form
      Hulle cells and cleistothecia, even in a liquid culture. These results indicated
      that the veA gene is a positive regulator in sexual development and
      simultaneously a negative one in asexual development.

PMID- 12223192
TI  - An IQGAP-related protein, encoded by AgCYK1, is required for septation in the
      filamentous fungus Ashbya gossypii.
AB  - In filamentous ascomycetes hyphae are compartmentalized by septation in which the
      cytoplasm of the compartments are interconnected via septal pores. Thus,
      septation in filamentous fungi is different from cytokinesis in yeast like fungi.
      We have identified an Ashbya gossypii orthologue of the Saccharomyces cerevisiae
      CYK1 gene which belongs to the IQGAP-protein family. In contrast to S. cerevisiae
      disruption of AgCYK1 yields viable mutant strains that exhibit wildtype-like
      polarized hyphal growth rates. In the Agcyk1 mutant cortical actin patches
      localize to growing hyphal tips like wildtype, however, mutant hyphae are totally
      devoid of actin rings at presumptive septal sites. Septation in wildtype results
      in the formation of chitin rings. Agcyk1 mutant hyphae are aseptate and do not
      accumulate chitin in their cell walls. Agcyk1 mutant strains are completely
      asporogenous indicating that septation is essential for the formation of
      sporangia in A. gossypii. AgCyk1p-GFP localizes to sites of future septation as a
      ring prior to chitin depositioning. Furthermore, decrease in Cyk1p-ring diameter
      was found to be a prerequisite for the accumulation of chitin and septum
      formation.

PMID- 12223193
TI  - Heterologous expression of the Aspergillus nidulans alcR-alcA system in
      Aspergillus niger.
AB  - The inducible and strongly expressed alcA gene encoding alcohol dehydrogenase I
      from Aspergillus nidulans was transferred together with the activator gene alcR,
      in the industrial fungus Aspergillus niger. This latter organism does not possess
      an inducible alc system but has an endogenously constitutive lowly expressed
      alcohol dehydrogenase activity. The overall induced expression of the alcA gene
      was of the same order in both fungi, as monitored by alcA transcription, alcohol
      dehydrogenase activity and heterologous expression of the reporter enzyme, beta
      glucuronidase. However, important differences in the pattern of alcA regulation
      were observed between the two fungi. A high basal level of alcA transcription was
      observed in A. niger resulting in a lower ratio of alcA inducibility. This may be
      due to higher levels of the physiological inducer of the alc regulon,
      acetaldehyde, from general metabolism in A. niger which differs from that of A.
      nidulans.

PMID- 12223194
TI  - The ukb1 gene encodes a putative protein kinase required for bud site selection
      and pathogenicity in Ustilago maydis.
AB  - Morphogenesis and pathogenesis are closely associated aspects of the life cycle
      of the fungal pathogen Ustilago maydis. In this fungus, the dimorphic switch from
      budding to filamentous growth coincides with the transition from non-pathogenic
      to pathogenic growth on maize. We have cloned and characterized the ukb1 gene
      that encodes a putative serine/threonine protein kinase with a role in budding
      and filamentous growth. Mutants defective in ukb1 were altered in bud site
      selection and produced lateral buds at a greater frequency than wild-type cells.
      Dikaryotic cells defective in ukb1 were capable of colonizing host tissue and
      growing with a filamentous morphology in planta. However, the mutants were
      incapable of inducing tumor formation and they failed to complete sexual
      development. In addition, the ukb1 gene influenced the ability of colonies to
      form aerial mycelia in response to environmental stimuli. Overall, the discovery
      of ukb1 reinforces the connection between morphogenesis and pathogenesis in U.
      maydis.

PMID- 12223195
TI  - Live-cell imaging of vegetative hyphal fusion in Neurospora crassa.
AB  - The process of hyphal fusion (anastomosis) in growing colonies of Neurospora
      crassa, stained with the membrane-selective dyes FM1-43 and FM4-64, was
      visualized by confocal microscopy. Time-lapse, live-cell imaging illustrated the
      dynamics of hyphal growth and anastomosis during its pre-contact, contact and
      post-contact, and post-fusion stages. Fusion-competent hyphae were
      morphologically distinct and exhibited remote sensing, resulting in branch
      initiation and/or re-direction of growth to facilitate contact between
      participating hyphae. A stained Spitzenkorper was often observed where fusion
      competent hyphae met. It is suggested that this structure contains secretory
      vesicles responsible for the delivery of cell adhesion molecules at the point of
      contact, cell wall synthesizing enzymes for the swelling growth of fused hyphal
      tips, and digestive enzymes required for fusion pore formation. Dramatic changes
      in cytoplasmic flow frequently occurred between the participating hyphae
      following fusion. After anastomosis has taken place, septa commonly formed close
      to the fusion site. The live-cell imaging reported here has clearly shown the
      complexity of the hyphal homing and fusion process. The control and consequences
      of repeated anastomoses within a mycelium must be as complex as the process
      itself.

PMID- 12223196
TI  - Suppression in function of phagocytic cells in common carp Cyprinus carpio L.
      injected with estradiol, progesterone or 11-ketotestosterone.
AB  - The modulation of phagocytic cells by beta-estradiol, 11-ketotestosterone,
      progesterone and cortisol was analysed in common carp (Cyprinus carpio L.). Carp
      were injected intraperitoneally (1 and 5 microg/kg fish) with each steroid and
      the activity of kidney macrophages was recorded 1 and 3 days post-injection.
      Bovine serum albumin-injected fish served as controls. Phagocytosis, superoxide
      anion and nitric oxide production were suppressed in all sex steroid treatments,
      and the suppression was in a dose-dependent manner. Cortisol treatment also
      inhibited the immune parameters to an extent similar to each of the steroid
      hormone. These results show that sex steroids can modulate the function of the
      phagocytic cells.

PMID- 12223197
TI  - Possible factors responsible for the toxicity of Cochlodinium polykrikoides, a
      red tide phytoplankton.
AB  - Cochlodinium polykrikoides, a harmful red tide dinoflagellate, is highly toxic to
      fish, but the toxic mechanism is still unknown. Recent study has suggested that
      C. polykrikoides generates reactive oxygen species (ROS) such as superoxide anion
      (O(2)(-)) and hydrogen peroxide (H(2)O(2)), and the ROS-mediated ichthyotoxicity
      has been proposed. In this study, we found that the levels of O(2)(-) and
      H(2)O(2) detected in C. polykrikoides were trace levels as compared with those of
      Chattonella marina which is well-known to produce ROS. Furthermore, no
      significant increase in O(2)(-) generation by C. polykrikoides was observed in
      the presence of lectins such as concanavalin A (Con A) and wheat germ agglutinin
      (WGA) or fish mucus prepared from skin and gill of yellowtail, whereas C. marina
      generated increased level of O(2)(-) responding to these stimuli. Interestingly,
      the cell-free aqueous extract prepared from C. polykrikoides showed toxic effect
      on the HeLa cells, but the extract of C. marina had no significant effect.
      Furthermore, gradual accumulation of polysaccharides in the medium was observed
      during the growth of C. polykrikoides, and the medium gradually became viscous,
      but no such changes were observed in the medium of C. marina. These results
      suggest that multiple factors may be responsible for the toxic mechanism of C.
      polykrikoides.

PMID- 12223198
TI  - Metabolic disturbances in fish exposed to sodium pentachlorophenate (NaPCP) and
      3,3',4,4',5-pentachlorobiphenyl (PCB126), individually or combined.
AB  - The Swan River Estuary is the recipient of multiple urban and agricultural
      contaminants which have the potential to induce liver detoxication enzymes as
      well as altering the metabolism of aquatic organisms. To test if altered liver
      metabolism would influence liver detoxication capacities, pink snapper (Pagrus
      auratus) were i.p. injected with peanut oil (controls), or pentachlorobiphenyl
      #126 (PCB126), with sodium pentachlorophenate (NaPCP), or PCB126+NaPCP. Relative
      to controls, ethoxyresorufin-O-deethylase (EROD) activity was induced in the
      PCB126 and PCB126+NaPCP fish, but not in the NaPCP group. In the liver,
      cytochrome c oxidase (CCO) activity was enhanced by the treatments while citrate
      synthase (CS) activity remained unchanged and lactate dehydrogenase (LDH)
      activity was increased in the NaPCP treatment only. The results suggest that
      liver CCO activity may be a suitable biomarker of effect following exposure to
      PCBs or phenolic compounds. In the white muscle, only the PCB126+NaPCP treatment
      enhanced CCO activity, with all other enzymatic activities remaining unchanged.
      It appears that the resilience to metabolic perturbations is greater for white
      muscle than for liver. Low serum sorbitol dehydrogenase (sSDH) activity and
      histopathology of the liver indicated no significant alteration of cellular
      structure, albeit the lipid droplet size was increased in the PCB126 and in the
      PCB126+NaPCP treatments. It is concluded that the hepatic metabolic changes
      correspond to histopathological observations, but an altered metabolic capacity
      do not influence the metabolism of xenobiotics by liver enzymes, as measured by
      EROD activity.

PMID- 12223199
TI  - Effect of gender differences and voluntary exercise on antioxidant capacity in
      rats.
AB  - The effects of gender difference and voluntary exercise on antioxidant capacity
      in rats were evaluated. The subjects were divided into two groups, physically
      active and sedentary. In the sedentary group, the level of hydroxyl radical in
      the liver was higher (P<0.001) in male rats than in female rats, however, in the
      physically active group, the level in male rats was lower (P<0.05) than in female
      rats. The levels of reduced glutathione (GSH) in physically active males and
      females were higher compared to those in the sedentary group. The physically
      active group also showed an increase in antioxidant enzymes, such as glutathione
      peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase activities.
      The level of liver GSH was higher in physically active females than in physically
      active males. For both groups, GPx and GR activities in females were
      significantly higher than in males. These results indicate that female rats have
      an intrinsically higher antioxidant capacity, which resulted in increased levels
      of GSH via the glutathione redox cycle and gamma-glutamyl cycle enzymes. The
      adaptation to altered antioxidant capacity, induced by physical activity,
      appeared to be affected by gender differences.

PMID- 12223200
TI  - Mixed function oxidases in kidney and duodenum of camel, guinea pig and rat.
AB  - The activities of the drug-metabolizing enzymes, aniline 4-hydroxylase,
      benzphetamine N-demethylase and 7-ethoxycoumarin O-deethylase have been measured
      in vitro in kidneys and duodenum of camels (Camelus dromedarius), guinea pigs
      (Cavia porcellus) and rats (Rattus norvegicus). In these species, levels of
      hepatic microsomal parameters namely microsomal protein, cytochrome P(450),
      cytochrome b(5) and NADPH-cytochrome c reductase have also been determined. In
      general, camels seemed to have the lowest enzyme activity when compared to rats
      and guinea pigs. Rats showed the highest activity in NADPH-cytochrome c
      reductase, aniline 4-hydroxylase and ethoxycoumarin O-deethylase among these
      species. However, guinea pigs showed the highest enzyme activity in cytochrome
      P(450), cytochrome b(5) and benzphetamine N-demethylase.

PMID- 12223201
TI  - Proliferative effects of angiotensin II and endothelin-1 on guinea pig gingival
      fibroblast cells in culture.
AB  - We investigated whether phenytoin (PHT) and nifedipine (NIF) induce angiotensin
      II (Ang II) and endothelin-1 (ET-1) generation by cultured gingival fibroblasts
      derived from guinea pigs and whether Ang II and ET-1 induce proliferation of
      these cells. Immunohistochemical experiments showed that PHT (250 nM) and NIF
      (250 nM) increased the immunostaining intensities of immunoreactive Ang II and ET
      1 (IRET-1) in these cells. Captopril (3 microM), an angiotensin-converting enzyme
      inhibitor, reduced these enhanced intensities to control levels. Ang II (100 nM)
      enhanced the immunostaining intensity of IRET-1. PHT (250 nM) and NIF (250 nM)
      induced cell proliferation. Both PHT- and NIF-induced proliferation was inhibited
      by captopril (3 microM). Ang II (100 nM) and ET-1 (100 nM) also induced cell
      proliferation. Ang II-induced proliferation was inhibited by CV11974 (1 microM),
      an AT(1) receptor antagonist and saralasin (1 microM), an AT(1)/AT(2) receptor
      antagonist, but not by PD123,319 (1 microM), an AT(2) receptor antagonist. ET-1
      induced proliferation was inhibited by BQ123 (10 microM), an ET(A) receptor
      antagonist, but not by BQ788 (1 microM), an ET(B) receptor antagonist. These
      findings suggest that PHT- and NIF-induced gingival fibroblast proliferation is
      mediated indirectly through the induction of Ang II and ET-1 and probably
      mediated through AT(1) and ET(A) receptors present in or on gingival fibroblasts.

PMID- 12223202
TI  - Dose and time-related in vitro effects of glucocorticoid on phagocytosis and
      nitrite release by splenic macrophages of wall lizard Hemidactylus flaviviridis.
AB  - Glucocorticoids (GC) are usually considered to be immunosuppressive and anti
      inflammatory. However, recent studies in mammals have demonstrated the diverse
      effects of GC on non-specific host-defense mechanism, depending on dose or
      duration of treatment. Hence, in the present study in vitro dose and time-related
      effects of glucocorticoid, i.e. hydrocortisone (HC) on phagocytosis and nitrite
      production by LPS-induced splenic macrophages in wall lizard Hemidactylus
      flaviviridis has been investigated. Hydrocortisone suppressed percentage
      phagocytosis, phagocytic index and nitrite production by splenic macrophages even
      at the lowest concentration (10(-13) M) for a short-term exposure (4 h).
      Hydrocortisone-induced suppression enhanced with the increase of concentration or
      duration of exposure time. The suppressive effect of hydrocortisone on phagocytic
      and cytotoxic activities of splenic macrophages was further corroborated since
      the pre-exposure of macrophages to glucocorticoid-receptor blocker (RU 486)
      considerably reduced the hydrocortisone-induced suppression of phagocytosis and
      nitrite production. The present study suggests that GC instead of diverse
      effects, has dose- and time-dependent immunosuppressive effect on non-specific
      host-defense immune responses in wall lizard H. flaviviridis.

PMID- 12223203
TI  - Modulation by ammonium ions of gill microsomal (Na+,K+)-ATPase in the swimming
      crab Callinectes danae: a possible mechanism for regulation of ammonia excretion.
AB  - The modulation by Na(+), K(+), NH(4)(+) and ATP of the (Na(+),K(+))-ATPase in a
      microsomal fraction from Callinectes danae gills was analyzed. ATP was hydrolyzed
      at high-affinity binding sites at a maximal rate of V=35.4+/-2.1 Umg(-1) and
      K(0.5)=54.0+/-3.6 nM, obeying cooperative kinetics (n(H)=3.6). At low-affinity
      sites, the enzyme hydrolyzed ATP obeying Michaelis-Menten kinetics with
      K(M)=55.0+/-3.0 microM and V=271.5+/-17.2 Umg(-1). This is the first
      demonstration of a crustacean (Na(+),K(+))-ATPase with two ATP hydrolyzing sites.
      Stimulation by sodium (K(0.5)=5.80+/-0.30 mM), magnesium (K(0.5)=0.48+/-0.02 mM)
      and potassium ions (K(0.5)=1.61+/-0.06 mM) exhibited site-site interactions,
      while that by ammonium ions obeyed Michaelis-Menten kinetics (K(M)=4.61+/-0.27
      mM). Ouabain (K(I)=147.2+/-7.microM) and orthovanadate (K(I)=11.2+/-0.6 microM)
      completely inhibited ATPase activity, indicating the absence of contaminating
      ATPase and/or neutral phosphatase activities. Ammonium and potassium ions
      synergistically stimulated the enzyme, increasing specific activities up to 90%,
      suggesting that these ions bind to different sites on the molecule. The presence
      of each ion modulates enzyme stimulation by the other. The modulation of
      (Na(+),K(+))-ATPase activity by ammonium ions, and the excretion of NH(4)(+) in
      benthic crabs are discussed.

PMID- 12223204
TI  - Induction of vitellogenesis in 17alpha-ethinylestradiol-exposed rainbow trout
      (Oncorhynchus mykiss): a method comparison.
AB  - Juvenile rainbow trout, Oncorhynchus mykiss, were exposed to the synthetic
      estrogen 17alpha-ethinylestradiol (EE(2)) through injection (1, 10, 25 and 50
      microg EE(2)/g fish/week) and via water exposure (1, 10 and 100 ng EE(2)/l).
      After seven (injection and water exposure) and 14 days (only for water exposure),
      blood and plasma vitellogenin concentrations were quantified using indirect
      endpoints, i.e. plasma alkaline-labile phosphorus (ALP), plasma protein and
      plasma calcium. In addition, the relative gonad (GSI) and liver weight (HSI) were
      recorded. Actual plasma vitellogenin concentrations were measured with an enzyme
      immunoassay. Only fish injected with 50 microg EE(2)/g fish had a significantly
      higher gonad weight. No concentration-dependent changes in the HSI were detected
      in fish exposed via the water, but a significant dose-dependent increase of the
      HSI was observed in fish injected with EE(2). Exposure of rainbow trout to EE(2)
      had a significant effect on all tested plasma parameters. Plasma protein,
      phosphoprotein and calcium concentrations were significantly higher after two
      weeks exposure to 100 ng EE(2)/l. Fish injected with 10, 25 and 50 microg EE(2)/g
      fish exhibited increased plasma protein concentrations after 1 week. Compared to
      the controls, plasma ALP and calcium levels were significantly higher in all
      injected fish. A significant and positive correlation was observed between all
      three plasma parameters and between these indirect parameters and the actual
      plasma vitellogenin concentrations. These findings indicate that both the plasma
      ALP and the plasma calcium assay have a similar sensitivity as that of available
      antibody-based assays (EIA), at least in EE(2) exposure studies, and thus these
      assays can provide a rapid, simple and cost-effective alternative to available
      immunoassays.

PMID- 12223205
TI  - Breed differences in growth hormone and insulin secretion between lactating
      Japanese Black cows (beef type) and Holstein cows (dairy type).
AB  - This study was performed to clarify the levels of growth hormone (GH) and insulin
      (INS) secretions and the glucose response to INS during lactation in a
      representative beef breed in Japan, Japanese Black cows, and to compare them with
      their counterparts in a dairy breed, Holstein cows. Six Japanese Black and seven
      Holstein primiparous cows received a single intravenous injection of GH-releasing
      factor (GRF; 0.25 microg/kg), glucose (112.5 mg/kg), or INS (0.2 U/kg) from late
      pregnancy (2 weeks antepartum) to mid-lactation (6 months postpartum). Japanese
      Black cows had one-tenth of the total milk yield of Holstein cows during
      lactation, and significantly lower GRF-induced GH and higher glucose-induced INS
      secretions than Holstein cows at all stages. In Japanese Black cows, even with
      lactation, these secretions remained essentially unchanged, whilst Holstein cows
      showed higher GH and lower INS secretions after the onset of lactation as
      compared with cows in late pregnancy. Both breeds had similar glucose response to
      INS at the respective stages. These results suggest that, during lactation,
      Japanese Black cows may minimize the catabolic effects of GH and sustain the
      anabolic effects of INS, in contrast with Holstein cows, but have similar ability
      to inhibit INS-mediated glucose utilization in peripheral tissues to Holstein
      cows.

PMID- 12223207
TI  - Expression of proton-pumping nicotinamide nucleotide transhydrogenase in mouse,
      human brain and C elegans.
AB  - Proton-translocating nicotinamide nucleotide transhydrogenase is located in the
      mitochondrial inner membrane and catalyzes the reduction of NADP(+) by NADH to
      NADPH and NAD(+). The present investigation describes the expression of the
      transhydrogenase gene in various mouse organs, subsections of the human brain and
      Caenorhabditis elegans. In the mouse, the expression was highest in heart tissue
      (100%) followed by kidney (64%), testis (52%), adrenal gland (41%), liver (35%),
      pancreas (34%), bladder (26%), lung (25%), ovary (21%) and brain (14%). The
      expression in brain tissue was further investigated in the human brain which
      showed a distribution that apparently varied as a function of neuronal density, a
      result that was supported by estimations of expression in C. elegans using Green
      Fluorescent Protein (GFP) controlled by the transhydrogenase promoter. GFP
      expressing C. elegans lines showed a clear concentration of fluorescence to the
      gut, the pharyngeal-intestinal valve and certain neurons. It is concluded that
      the transhydrogenase gene is expressed to various extents in all cell types in
      mouse, human and C. elegans.

PMID- 12223206
TI  - Molecular analysis of the bison phagocyte NADPH oxidase: cloning and sequencing
      of five NADPH oxidase cDNAs.
AB  - During the host defense process, neutrophils migrate into infected tissues where
      they become activated, resulting in the assembly of a superoxide anion-generating
      complex known as the NADPH oxidase. Despite the importance of this system in
      animal host defense, almost nothing is known about the NADPH oxidase in
      neutrophils from wild ruminant species. In the present studies, we provide a
      molecular analysis of the bison leukocyte NADPH oxidase. Using reverse
      transcriptase-polymerase chain reaction and rapid amplification of cDNA ends, we
      cloned and sequenced the full-length cDNAs for five bison NADPH oxidase
      components: p22(phox), p40(phox), p47(phox) and p67(phox), and gp91(phox). When
      compared to other species, the deduced amino acid sequences of the bison homologs
      were most similar to those of bovine. Interestingly, a bison p40(phox)
      alternative splice product was isolated, which was similar to that observed for
      human p40(phox) in that the cDNAs contained sequence from intron 8. Consistent
      with the high degree of similarity between bison and bovine amino acid sequences,
      immunoblot analysis showed that the bison homologs migrated similarly to their
      bovine counterparts. Overall, these studies show that the bison and bovine NADPH
      oxidase genes are highly conserved between these two species, despite their
      divergence from a common ancestor over 1 million years ago.

PMID- 12223208
TI  - Extramitochondrial localization of NADH-fumarate reductase in trypanosomatids.
AB  - Trypanosoma brucei procyclic trypomastigotes and T. cruzi epimastigotes (both
      Tulahuen and Y strains) were permeabilized by incubation with increasing amounts
      of digitonin, causing enzymes to be released from different intracellular
      compartments. After 10 min incubation with digitonin, the cells were centrifuged
      and the activity of marker enzymes (aspartate-dependent malic enzyme for
      cytoplasm, hexokinase for glycosomes and either isocitrate dehydrogenase or
      citrate synthase for mitochondria) was analyzed in the supernatant. The results
      were compared with the release of NADH-fumarate reductase in order to determine
      if this enzyme was preferentially released with a specific intracellular marker.
      Fumarate reductase was released at lower digitonin concentration than those
      required to either release isocitrate dehydrogenase or citrate synthase.
      Similarly, Leishmania donovani promastigotes (S-2 strain) were exposed to a
      single concentration of digitonin (200 micro M) but in this case we monitored the
      release of fumarate reductase and hexokinase, while monitoring the mitochondrial
      membrane potential (using safranine O). Again, substantial fumarate reductase and
      hexokinase activities were released without loss of mitochondrial membrane
      potential indicating that part of the enzyme was released while the inner
      mitochondrial membrane remained intact. These results suggest that, in the three
      species of trypanosomatids the enzyme fumarate reductase is, at least in part,
      located outside the mitochondrial matrix.

PMID- 12223209
TI  - A bacterial TMAO transporter.
AB  - Trimethylamine oxide (TMAO) acts as an osmolyte in a wide variety of marine
      organisms, but little is known about the mechanisms by which it accumulates in
      certain tissues. To determine whether a TMAO-specific transporter occurs in
      Nature, we examined a bacterium Aminobacter aminovorans that is known to be able
      to subsist on methylamine as the sole carbon source. We found that A. aminovorans
      is also able to grow on TMAO as the sole carbon source, and that it takes up
      [14C]labeled TMAO at a rate of approximately 50 pmol min(-1) x mg protein(-1).
      TMAO uptake was strongly inhibited by unlabeled TMAO (5 mM) but not by related
      compounds such as methylamine, betaine or gamma-amino-n-butyric acid (GABA),
      indicating that a TMAO-specific transporter is present. The TMAO transporter
      appears to have an ATP requirement but no ion exchange requirement. This appears
      to be the first evidence of a TMAO-specific transporter in any organism. The TMAO
      grown cells also expressed transporters that were specific to betaine and
      trimethylamine. Madin-Darby canine kidney (MDCK) cells, which have a betaine
      transporter that is also capable of transporting GABA, were unable to take up
      TMAO.

PMID- 12223210
TI  - Temperature and Ca(2+)-dependence of the sarcoplasmic reticulum Ca(2+)-ATPase in
      haddock, salmon, rainbow trout and zebra cichlid.
AB  - Temperature dependence of Ca(2+)-ATPase from the sarcoplasmic reticulum (SR) in
      rabbit muscle has been widely studied, and it is generally accepted that a break
      point in Arrhenius plot exist at approximately 20 degrees C. Whether the break
      point arises as a result of temperature dependent changes in the enzyme or its
      membrane lipid environment is still a matter of discussion. In this study we
      compared the temperature dependence and Ca(2+)-dependence of SR Ca(2+)-ATPase in
      haddock (Melanogrammus aeglefinus), salmon (Salmo salar), rainbow trout
      (Oncorhynchus mykiss) and zebra cichlid (Cichlasoma nigrofasciatum). The
      Arrhenius plot of zebra cichlid showed a break point at 20 degrees C, and the
      haddock Arrhenius plot was non-linear with pronounced changes in slope in the
      temperature area, 6-14 degrees C. In Arrhenius plot from both salmon and rainbow
      trout a plateau exists with an almost constant SR Ca(2+)-ATPase activity. The
      temperature range of the plateau was 14-21 and 18-25 degrees C in salmon and
      rainbow trout, respectively. Ca(2+)-dependence in the four different fish species
      investigated was very similar with half maximal activation (K(0.5)) between 0.2
      and 0.6 micro M and half maximal inhibition (I(0.5)) between 60 and 250 micro M.
      Results indicated that interaction between SR Ca(2+)-ATPase and its lipid
      environment may play an important role for the different Arrhenius plot of the
      different types of fish species investigated.

PMID- 12223211
TI  - Biosynthesis of steroids in ovarian follicles of red seabream, Pagrus major
      (Sparidae, Teleostei) during final oocyte maturation and the relative
      effectiveness of steroid metabolites for germinal vesicle breakdown in vitro.
AB  - The steroid synthesis pathway in the ovarian follicles of the red seabream during
      final oocyte maturation (FOM) was investigated by incubating intact follicles
      with different radioactively labeled steroid precursors. During FOM, the
      steroidogenic shift from estradiol-17beta to 20 beta-hydroxylated progestin
      production occurred mainly due to a combination of inactivation of C 1720-lyase
      and activation of 20 beta-hydroxysteroid dehydrogenase. Of the steroids produced,
      1720 beta-dihydroxy-4-pregnen-3-one (1720 beta-P) and 1720 beta,21-trihydroxy-4
      pregnen-3-one (20 beta-S) exhibited the greatest effect on germinal vesicle
      breakdown (GVBD) in vitro. 1720 beta-P was further converted to its 5 beta
      reduced form, 1720 beta-dihydroxy-5 beta-pregnan-3-one (1720 beta-P-5 beta),
      which had lower GVBD activity, suggesting that 5 beta-reduction plays a role in
      the inactivation of the maturation-inducing ability of 1720 beta-P. In contrast,
      no 5 beta-reduced metabolite of 20 beta-S was found. Serum levels of 1720 beta-P
      and 20 beta-S, measured by ELISA, showed that circulating levels of both
      progestins increased during FOM, and 20 beta-S levels were approximately twice as
      high as 1720 beta-P levels. This study clarified the complete steroidogenesis
      pathway during FOM in red seabream ovarian follicles and showed that two 20 beta
      hydroxylated progestins, 1720 beta-P and 20 beta-S, act as maturation-inducing
      hormones in this species. The catabolites of these two progestins and their
      physiological roles in reproduction are also discussed.

PMID- 12223212
TI  - Binding of polycyclic aromatic hydrocarbons (PAHs) to teleost aryl hydrocarbon
      receptors (AHRs).
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous, environmental
      contaminants that pose a potential risk to fish populations. Both field and
      laboratory studies suggest that exposure of the early life stages of fish to PAH
      can mimic the embryotoxic effects of the planar halogenated hydrocarbons (PHHs),
      the most potent of which is 2,3,7,8-tetrachlorodibenzo-p-dioxin. PHH toxicity is
      mediated by the aryl hydrocarbon receptor (AHR) and PHH potency is predicted by
      its AHR-binding affinity and CYP1A induction potency. However, the role of the
      AHR, if any, in mediating the developmental effects of PAH to fish remains
      unknown. In this study we looked at the AHR binding affinity of a test set of PAH
      that had been previously ranked for their potency for inducing teleost CYP1A. PAH
      that induced CYP1A inhibited [3H]TCDD binding to in vitro-expressed AHRs from
      rainbow trout and the AHR expressed in PLHC-1 fish hepatoma cells. Generally, the
      relative rank order for AHR binding affinity predicted the rank order of these
      same PAH for inducing CYP1A reported in other studies. There was a strong,
      positive relationship between binding to the PLHC-1 AHR (stimulus) and the EC50s
      for CYP1A induction (response) in whole juvenile trout and in RTL-W1 cells, but
      EC50s were much higher than expected for a 1:1 stimulus/response relationship.
      These data show that the ability of PAH to bind to teleost AHR predicts PAH
      potency for CYP1A induction. If PAH toxicity is receptor-mediated and predicted
      by induction potencies, we will have a powerful mechanistic-based tool for
      rapidly assessing the risk of toxicity to fish of PAH from any source.

PMID- 12223213
TI  - Proteolytic substructure of myorod, a thick filament protein of molluscan smooth
      muscles.
AB  - Myorod (MR), a new thick filament protein of molluscan smooth muscles, is an
      alternatively spliced product of the myosin (Mn) heavy chain gene. We studied
      digestion of MR and Mn from the posterior adductor of Crenomytilus grayanus and
      the outer portion of adductor of Mizuchopecten (Patinopecten) yessoensis by
      papain and constructed the proteolytic substructure of MR, that is an analogue to
      Mn substructure. There are a head domain (analogue of Mn S1) and a rod domain
      (analogue of Mn rod); the junction between them is split at low ionic strength.
      The rod, in turn, consists of a neck domain (analogue of Mn S2) and a tail domain
      (identical to light meromyosin); the junction between them is split at high ionic
      strength. The localization and possible function of MR are discussed.

PMID- 12223214
TI  - Distribution of rod- and cone-specific phosducins in retinas of non-mammalian
      vertebrates.
AB  - In mammalian retinas, it has been believed that just one kind of phosducin (PD)
      commonly exists in both rods and cones. However, we have previously reported that
      there are rod- and cone-specific PDs (OlPD-R and OlPD-C) in medaka (Oryzias
      latipes) retina [FEBS Lett., 502, 117-121, 2001]. To clarify the distribution and
      evolution of these photoreceptor type-specific PDs, we investigated PDs of
      another teleost and a reptile. Immunohistochemical and Western blot analyses
      using anti-medaka PD antisera demonstrated that two kinds of PDs are expressed in
      zebrafish (Danio rerio) photoreceptor cells. Our study is suggestive that
      teleosts generally possess rod- and cone-specific PDs. We isolated a cDNA
      encoding putative PD (PmlPD) of a diurnal gecko (Phelsuma madagascariensis
      longinsulae). Because diurnal gecko possesses a pure-cone retina, it was expected
      that PmlPD would be expressed in cones. Molecular phylogenetic analysis
      demonstrated that PmlPD was more closely related to mammalian PDs than teleost
      cone-specific PDs, suggesting that the rod- and cone-specific subtype of teleost
      PDs have arisen after the teleost-tetrapod divergence.

PMID- 12223215
TI  - Cloning of hibernation-related genes of bullfrog (Rana catesbeiana) by cDNA
      subtraction.
AB  - Seven genes specifically expressed during hibernation in the bullfrog (Rana
      catesbeiana) were cloned from a subtracted cDNA library constructed from livers
      of winter bullfrogs. Those genes were fibrinogen alpha-subunit, fibrinogen gamma
      subunit, complement component C3, alpha-1-microglobulin/bikunin precursor (AMBP),
      transferrin, apoferritin middle subunit and one novel gene. Northern
      hybridization has indicated that these seven genes were specifically induced or
      enhanced in winter. Above all, expression of the novel gene was specifically
      induced in winter in liver, though the expression of that was neither induced in
      bullfrog nor Xenopus laevis by cold treatment. The novel gene, which was
      designated as rc-hirp (Rana catesbeiana hibernation-related protein), encoded 420
      base pairs length and a putative protein of 139 amino acid residues. Annual
      analyses of the expression of these genes have suggested that the seven winter
      specific genes are playing an important role in hibernation processes.

PMID- 12223216
TI  - Mutation or deletion of the C-terminal tail affects the function and structure of
      Xenopus laevis small heat shock protein, hsp30.
AB  - Small heat shock proteins (shsps) act as molecular chaperones by preventing heat
      induced aggregation and unfolding of cellular proteins by a mechanism that is
      still unclear. Previously we found that the C-terminal end of Xenopus shsp,
      hsp30C (30C), was essential for optimal chaperone activity. Examination of the C
      terminal tail of 30C revealed that it had a net negative charge. Involvement of
      this negative charge in chaperone activity was assessed by the creation of two
      mutants, D209G (Asp converted to the more neutrally charged and less polar Gly at
      position 209) and D209/213G (Asp to Gly at position 209 and 213). Compared to 30C
      and D209G, D209/213G was impaired in inhibiting heat-induced citrate synthase
      aggregation. In rabbit reticulocyte lysate and Xenopus oocyte microinjection
      refolding assays the mutants were not as efficient as 30C in maintaining heat
      treated luciferase in a folding competent state. Circular dichroism analysis
      revealed that D209G was similar in secondary structure to 30C whereas D209/213G
      displayed a loss of alpha-helical-like and beta-sheet structure. Also, C-terminal
      truncation of 30C or 30D (an hsp30 isoform) resulted in a loss of secondary
      structure and function. This study clearly shows that mutation of aspartic acid
      residues in the C-terminal end of hsp30 or its truncation disrupts secondary
      structure and impairs its chaperone activity.

PMID- 12223217
TI  - Presence of alpha1-antitrypsin and transferrin in human follicular fluid-
      correlation with fertilization.
AB  - We purified two proteins with molecular masses of approximately 50 kDa and 80 kDa
      with N-terminal sequences similar to those of alpha1-antitrypsin (a1AT) and
      transferrin indicating that they are identical to or highly homologous to these
      proteins. Proteins from human follicular fluid were purified after ammonium
      sulfate fractionation followed by water dialysis and High Performance Liquid
      Chromatography. The fraction of peak 3 showed a single band on electrophoresis
      and its N-terminal amino acid sequence was similar to that of human serum
      transferrin. The fraction of peak 10 proved to be a glycoprotein and its N
      terminal amino acid sequence was similar to that of human serum a1AT. There are
      indications that transferrin may be involved in the fertilization process. Sperm
      motion was assessed employing computer-assisted semen analysis. The addition of
      purified protein to prepared sperm samples from normospermic men significantly
      increases the straight-line velocity (VSL), the amplitude of lateral head
      displacement (ALH) and the number of progressively motile sperm. a1AT does not
      seem to have a stimulatory effect on sperm motility.

PMID- 12223218
TI  - Detection of procathepsin D in rat milk.
AB  - The presence of procathepsin D, a zymogen of the soluble lysosomal aspartic
      proteinase cathepsin D, was detected in rat milk using Western blot analysis and
      assay of proteolytic activity in acidic buffers. No other forms of cathepsin D
      were found. Two different polyclonal anti-procathepsin D antibodies were used for
      immunochemical detection of procathepsin D. Both antibodies we found to recognize
      rat procathepsin D. Proteolytic activity in acidic buffers was detected using a
      fluorogenic substrate specific for cathepsin D and was abolished by pepstatin A,
      a specific inhibitor of aspartic proteinases. This study represents third
      demonstration of presence of procathepsin D in mammal breast milk. Potential
      sources and physiological functions are discussed.

PMID- 12223219
TI  - Islet amyloid polypeptide is expressed in the pancreatic islet parenchyma of the
      teleostean fish, Myoxocephalus (cottus) scorpius.
AB  - The comparative endocrinology of the 37-amino-acid-residue islet amyloid
      polypeptide (IAPP) is poorly known, possibly due to the fact that available
      antisera, raised against mammalian IAPP, fail to give immunoreactivity with islet
      parenchymal cells of non-mammalian vertebrates. Using reverse transcriptase
      linked polymerase chain reaction with degenerate primers, IAPP was identified,
      and its deduced amino-acid sequence partially characterized, in three species of
      teleostean fish, i.e. Danio rerio (zebrafish), Salmo salar (Atlantic salmon), and
      Myoxocephalus (cottus) scorpius (daddy sculpin). The daddy sculpin is a species
      where the histophysiology of the pancreatic islet parenchyma has previously been
      comprehensively studied. From the deduced amino-acid sequence, a synthetic
      peptide, corresponding to positions 20-29 of Salmo IAPP, was synthesized. A mouse
      antiserum to this peptide gave a distinct immunoreactivity with the insulin
      producing beta cells of the sculpin Brockmann bodies and salmon endocrine
      pancreas. Thus, IAPP belongs to the group of peptide hormones expressed by the
      islet parenchymal cells in both mammals and non-mammalian vertebrates. Salmo
      salar IAPP(20-29) was found to give rise to amyloid-like fibrils in vitro.

PMID- 12223220
TI  - Estrous cycle-regulated expression of CYP1B1 mRNA in the rat ovary.
AB  - CYP1B1, a member of the cytochrome p450 superfamily, is expressed constitutively
      in the steroidogenic tissues of mammals and is inducible by peptide hormones,
      cAMP and aromatic hydrocarbon receptor (AHR) ligands. The mechanism of induction
      of this cytochrome p450 is similar to that for CYP1A1, i.e. through the aromatic
      hydrocarbon receptor (AHR) signaling pathway. We have recently reported that
      CYP1B1, but not CYP1A1, is expressed in rat granulosa cells (GC) in the absence
      of any external stimulus. The induction of CYP1B1 mRNA in rat GC by 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) in vitro was followed by an increase in AHR
      and estrogen receptor (ER-beta) RNA levels. Estrous cycle-dependent expression of
      AHR, AHR-nuclear translocator (ARNT) and ER-mRNAs in the rat ovary was reported.
      We suggest that CYP1B1 may play a major role in the regulation of rat ovarian
      function/cycle but until now this has been unexplored experimentally. The present
      study was therefore aimed at examining the expression of CYP1A1, CYP1B1 and ER
      mRNA in rat ovarian tissues throughout the estrous cycle to establish any
      correlation in the expressions of these mRNAs in rat ovary. Total RNA was
      extracted from the ovary and liver of cycling adult rats and the mRNAs were
      analyzed using relative RT-PCR with gene-specific primers for the target mRNA and
      for RPL 19 or S16 primers as an internal control. The results indicated that in
      the ovary, CYP1B1 mRNA increased significantly on the evening of proestrus and
      dramatically decreased on the morning of estrus, while ER-mRNA remained unaltered
      throughout the estrous cycle. CYP1A1 mRNA in the ovary and both CYP1A1 and CYP1B1
      mRNAs in the liver were undetectable. That the sudden decrease of ovarian CYP1B1
      mRNA on the morning of estrus was not an effect of the LH surge was verified in
      vitro using our short-term GC culture model. GC prepared from rats super
      stimulated with equine chorionic gonadotropin (eCG) were cultured for 6 h with or
      without LH and TCDD. It was observed that both CYP1A1 and CYP1B1 mRNAs were
      induced by TCDD with no apparent effect of LH. It is suggested that the high
      level of CYP1B1 mRNA expression on the evening of proestrus in rat ovary might be
      involved in metabolism of estrogens to catecholestrogen (a known effect of
      CYP1B1), and that expression is unaffected in GC by LH.

PMID- 12223221
TI  - Lysosomal glycosidases and their natural substrates in major salivary glands of
      hamsters treated with 7,12-dimethylbenzanthracene (DMBA).
AB  - Oro-maxillofacial diseases may influence structure and function of salivary
      glands. In this study, 32 hamsters were treated with topical application of 7,12
      dimethylbenzanthracene (DMBA) on the buccal pouch. After 16 weeks, the animals
      were killed and the major salivary glands extracted. The activities of some
      lysosomal glycosidases and their natural substrates were measured to understand
      how the carcinogenetic stress and the inflammatory reaction could influence the
      physiology of the salivary glands. Large differences were observed in lysosomal
      activities among treated and untreated animals. Similarly, large differences were
      shown in the concentration of natural substrates, including sialic acids. These
      results suggest that inflammation and/or tumors induce profound changes in the
      biology of the salivary glands.

PMID- 12223222
TI  - The role of neutrophil elastase in acute lung injury.
AB  - Beside its physiological function as a powerful host defense, neutrophil elastase
      is also known as one of the most destructive enzymes in the body. Current notion
      holds that neutrophil elastase is able to escape from regulation by multiple
      protease inhibitors at inflammatory sites. Once unregulated, this enzyme disturbs
      the function of the lung permeability barrier and induces the release of pro
      inflammatory cytokines. These actions then cause symptoms that are typical in the
      pathophysiology of acute lung injury. In this article, we review recent progress
      in the understanding of the physiological activity of neutrophil elastase and its
      role in acute lung injury. Evidence in this review that supports the involvement
      of neutrophil elastase in the pathophysiology of acute lung injury includes: (1)
      neutrophil elastase levels are increased in both clinical and animal models of
      acute lung injury; (2) topical or systemic administration of neutrophil elastase
      produces typical symptoms of acute lung injury both in vitro and in vivo; and (3)
      inhibition of increased neutrophil elastase activity reduces symptoms of acute
      lung injury in animal models. A greater understanding of the role of this enzyme
      in the pathophysiology of acute lung injury will lead to better treatments for
      this complicated disease.

PMID- 12223223
TI  - Avasimibe and atorvastatin synergistically reduce cholesteryl ester content in
      THP-1 macrophages.
AB  - Evidence suggests that the inhibition of both acyl-CoA:cholesterol
      acyltransferase and hydroxymethyl glutaryl-CoA reductase causes a synergistic
      direct antiatherosclerotic effect on the vessel wall. To investigate this
      synergism in a single cell type and to avoid the confounding effect of plasma
      cholesterol lowering by these drugs, we have used an in vitro model of human
      macrophages (phorbol ester-treated THP-1 cells). In macrophages incubated
      simultaneously with acetyl low-density lipoproteins, the novel acyl
      CoA:cholesterol acyltransferase inhibitor avasimibe (0.01-0.5 microM) caused a
      concentration-dependent reduction in cell cholesteryl ester content that was not
      accompanied by an increase in intracellular free cholesterol. A 5 microM
      concentration of atorvastatin enhanced by approximately twofold the ability of
      0.5 microM avasimibe to reduce the mass of esterified cholesterol, and this was
      reversed by co-incubation with 200 microM mevalonate or 10 microM geranyl
      geraniol. Based on these data, we propose that the synergism between acyl
      CoA:cholesterol acyltransferase and hydroxymethyl glutaryl-CoA reductase
      inhibitors found in several in vivo studies may be explained by a direct additive
      effect of both agents reducing the lipid content of the macrophages present in
      the lesion area.

PMID- 12223224
TI  - Enhancement of osteogenesis in vitro by a novel osteoblast differentiation
      promoting compound, TAK-778, partly through the expression of Msx2.
AB  - TAK-778 [(2R,4S)-(-)-N-(4-Diethoxyphosphorylmethylphenyl)-1,2,4,5-tetrahydro-4
      methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxamide: mw 505.52], a novel
      compound promoting osteoblast differentiation, promotes osteogenesis in vitro and
      enhances bone formation during skeletal repair in vivo. In this study, we further
      evaluated the effects of TAK-778 on the differentiation of cultured bone marrow
      stromal cells into osteoblasts in the presence of dexamethasone, paying
      particular attention to the expression of transcription factors involved in
      regulating osteoblast differentiation. Treatment of TAK-778 (10(-7)-10(-5) M) for
      4 h resulted in an increase in the mRNA expression of Msx2, but not Cbfa1 or
      Dlx5. This transcriptional alteration preceded the changes in other markers
      related to the osteoblast phenotype, such as alkaline phosphatase and osteocalcin
      mRNA. The transfection of Msx2-antisense in the cells caused a significant
      reduction in the levels of alkaline phosphatase mRNA expression induced by TAK
      778. These results suggest that TAK-778 promotes osteoblast differentiation
      partly through the expression of Msx2, a homeobox-related gene.

PMID- 12223225
TI  - Enhanced amphetamine-mediated dopamine release develops in PC12 cells after
      repeated amphetamine treatment.
AB  - We previously demonstrated that rats treated with repeated, intermittent
      amphetamine displayed enhanced amphetamine-mediated dopamine release in the
      striatum. In this study, we examined whether amphetamine pretreatment would
      elicit enhanced amphetamine-mediated dopamine release in a cultured cell line in
      the absence of intact synaptic connections. PC12 cells pretreated with 1 microM
      amphetamine produced over twofold increase in amphetamine-mediated dopamine
      release upon challenge with 1 microM amphetamine as compared with vehicle-treated
      cells. No change in norepinephrine transporter density or [3H]dopamine uptake was
      detected. A withdrawal time of 6 days was required to observe the enhanced
      amphetamine-mediated dopamine release. Differentiation of the cells with nerve
      growth factor did not alter the amphetamine-mediated dopamine release in control
      cells or the development of enhanced release in amphetamine-treated cells. Our
      results demonstrate that repeated, intermittent amphetamine leads to a
      neuroadaptation resulting in enhanced amphetamine-induced dopamine release in
      catecholaminergic cells without the need of an intact neuroanatomy.

PMID- 12223226
TI  - Zoniporide: a potent and highly selective inhibitor of human Na(+)/H(+) exchanger
      1.
AB  - We evaluated the in vitro pharmacological profile of a novel, potent and highly
      selective Na(+)/H(+) exchanger-1 (NHE-1) inhibitor, [1-(Quinolin-5-yl)-5
      cyclopropyl-1H-pyrazole-4-carbonyl]guanidine hydrochloride monohydrate
      (zoniporide or CP-597,396). The potency and selectivity of zoniporide were
      determined via inhibition of 22Na(+) uptake by PS-120 fibroblast cell lines
      overexpressing human NHE-1, -2 or rat NHE-3. Additionally, potency for endogenous
      NHE-1 was confirmed via ex vivo human platelet swelling assay (PSA), in which
      platelet swelling was induced by exposure to sodium propionate. The
      pharmacological profile of zoniporide was compared with that of eniporide and
      cariporide. Zoniporide inhibited 22Na(+) uptake in fibroblasts expressing human
      NHE-1 in a concentration-dependent manner (IC(50) = 14 nM) and was highly
      selective (157-fold and 15,700-fold vs. human NHE-2 and rat NHE-3, respectively).
      Zoniporide was 1.64- to 2.6-fold more potent at human NHE-1 than either eniporide
      or cariporide (IC(50) = 23 and 36 nM, respectively). Zoniporide was also more
      selective at inhibiting human NHE-1 vs. human NHE-2 than either eniporide or
      cariporide (157-fold selective compared with 27- and 49-fold, respectively). All
      three compounds inhibited human platelet swelling with IC(50) values in low
      nanomolar range. From these results, we conclude that zoniporide represents a
      novel, potent and highly selective NHE-1 inhibitor.

PMID- 12223227
TI  - GABA(A) receptor activation and open-channel block by volatile anaesthetics: a
      new principle of receptor modulation?
AB  - The rapid application of solutions containing the volatile anaesthetics
      isoflurane or sevoflurane induced inward currents in human embryonic kidney
      (HEK293) cells carrying rat recombinant alpha(1)beta(2)gamma(2L) GABA(A) receptor
      assemblies. The responses evoked by the anaesthetics applied via a fast delivery
      system were recorded using the patch-clamp technique in the whole-cell mode. The
      anaesthetics induced a fast inward current which was followed by a prominent tail
      current upon the rapid withdrawal of the agent. These currents were simulated
      using a kinetic scheme embodying two agonist-like binding steps required for
      receptor activation, and one binding step by which the anaesthetic induces an
      open-channel block. According to this model of a biphasic receptor modulation,
      the open-channel block delays the ion flux through the ligand-gated receptors
      and, thus, prolongs the overall duration of the current response. Open-channel
      blocks might also be operative in other ligand-gated ion channels to modulate
      synaptic strength.

PMID- 12223228
TI  - Role of GABA(A) receptors in the ethanol-mediated inhibition of extracellular
      signal-regulated kinase.
AB  - In the present study, we demonstrate the involvement of GABA(A) receptors in the
      ethanol-mediated modulation of extracellular signal-regulated kinases (ERK).
      Intraperitoneal (i.p.) administration of ethanol (3.5 g), flurazepam (75 mg) or
      (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cycloheptane-5,10-iminemaleate (MK
      801) (0.4 mg/kg body weight) decreased, while picrotoxin (10 mg/kg body weight)
      increased, the phosphorylation of ERK following 10 min of their injection.
      However, the picrotoxin-induced phosphorylation of ERK was inhibited by ethanol,
      but was not affected by MK-801. These results indicate that ethanol's inhibitory
      effect on ERK phosphorylation may involve the modulation of GABA(A) receptor
      function.

PMID- 12223229
TI  - Group III mGlu receptor agonists potentiate the anticonvulsant effect of AMPA and
      NMDA receptor block.
AB  - We report the anticonvulsant action in DBA/2 mice of two mGlu Group III receptor
      agonists: (R,S)-4-phosphonophenylglycine, (R,S)-PPG, a compound with moderate
      mGlu8 selectivity, and of (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic
      acid, ACPT-1, a selective agonist for mGlu4alpha receptors. Both compounds, given
      intracerebroventricularly at doses which did not show marked anticonvulsant
      activity, produced a consistent shift to the left of the dose-response curves
      (i.e. enhanced the anticonvulsant properties) of 1-(4'-aminophenyl)-3,5-dihydro
      7,8-dimethoxy-4H-2,3-benzodiazepin-4-one hydrochloride, CFM-2, a noncompetitive
      AMPA receptor antagonist, and 3-((+/-)-2-carboxypiperazin-4-yl)-1-phosphonic
      acid, CPPene, a competitive NMDA receptor antagonist, in DBA/2 mice. In addition,
      (R,S)-PPG and ACPT-1 administered intracerebroventricularly prolonged the time
      course of the anticonvulsant properties of CFM-2 (33 micromol/kg, i.p.) and
      CPPene (3.3 micromol/kg, i.p.) administered intraperitoneally. We conclude that
      modest reduction of synaptic glutamate release by activation of Group III
      metabotropic receptors potentiates the anticonvulsant effect of AMPA and NMDA
      receptor blockade.

PMID- 12223230
TI  - Role of nitric oxide in systemic effect of theophylline on mouse body
      temperature.
AB  - In the present study, the interaction of nitric oxide synthase (NOS) inhibitors,
      L-NAME (N(G)-nitro-L-arginine methyl ester HCl) and L-NA (N(omega)-nitro-L
      arginine), and its precursor, L-arginine (2-(S)-2-amino-5
      [(aminoiminomethyl)amino] pentatonic acid), with theophylline on mouse body
      temperature was studied. Intraperitoneal (i.p.) injection of different doses of
      theophylline altered body temperature. Lower doses of theophylline (12.5 and 25
      mg/kg) increased, but a higher dose (100 mg/kg) reduced, the animals' body
      temperature. The combination of L-arginine (20 and 40 mg/kg) with the highest
      dose of theophylline potentiated the hypothermic effect induced by the latter
      drug, while L-arginine by itself did not alter body temperature. L-NAME (10-80
      mg/kg) or L-NA (10 mg/kg) plus a lower dose of theophylline (12.5 mg/kg) reduced
      the theophylline-induced hyperthermic response. L-NA (1, 5, and 10 mg/kg) in
      combination with the high dose of theophylline (100 mg/kg) also induced greater
      hypothermia. Both L-NAME and L-NA by themselves reduced body temperature. It is
      concluded that nitric oxide (NO) may be involved in the effects of theophylline
      on body temperature in mice.

PMID- 12223231
TI  - Arylalkylamines are a novel class of positive allosteric modulators at GABA(B)
      receptors in rat neocortex.
AB  - Using grease-gap recording from rat neocortical slices, the gamma-aminobutyric
      acid(B) (GABA(B)) receptor agonists baclofen (3-100 microM) and SKF 97541 (3
      aminopropyl-methylphosphinic acid) (1-30 microM) elicited reversible and
      concentration-dependent hyperpolarizing responses, with EC(50) values of 10 and 3
      microM, respectively. The hyperpolarizations were antagonised by the GABA(B)
      receptor antagonist Sch 50911 ((+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid) (1,
      5 and 10 microM). Fendiline (N-[3,3-diphenylpropyl)-alpha-methylbenzylamine) (5
      50 microM) and its congeners, prenylamine (N-[3,3-diphenylpropyl)-alpha
      methylphenylethylamine) (10-100 microM) and F551 (N-[3,3-diphenylpropyl)-alpha
      methyl-3-methoxybenzylamine) (1-30 microM) reversibly enhanced hyperpolarizing
      responses to the agonists; such effects were reduced by Sch 50911. These
      arylalkylamines produced leftward shifts of the concentration-response curves,
      with a marked increase in the maximal hyperpolarization obtained, compared with
      the agonists alone, F551 being the most potent. These findings suggest that these
      arylalkylamines represent a new class of positive modulators of GABA(B) receptor
      mediated function.

PMID- 12223232
TI  - Endomorphins suppress nociception-induced c-Fos and Zif/268 expression in the rat
      spinal dorsal horn.
AB  - We evaluated the potency of endomorphin-1 and -2 as endogenous ligands on c-Fos
      and Zif/268 expression in the spinal dorsal horn by formalin injection to the rat
      hind paw. Endomorphin-1, -2, or morphine was administered intrathecally or
      intracerebroventricularly 5 min before formalin injection (5%, 100 microl). All
      drugs produced marked reductions of formalin-induced c-Fos and Zif/268
      immunoreactivity in laminae I and II, and laminae V and VI in the rat lumbar
      spinal cord. The reductions of Zif/268 expression by endomorphins were greater
      than those by morphine, while the reductions of c-Fos expression by endomorphins
      were smaller than those by morphine. These effects of endomorphins were
      attenuated by pretreatment with naloxone. These results indicate that endomorphin
      1 and -2 act as endogenous ligands of mu-opioid receptor in neurons of the spinal
      dorsal horn and suppress the processing of nociceptive information in the central
      nervous system.

PMID- 12223233
TI  - Mediators of adenosine- and ovalbumen-induced bronchoconstriction of sensitized
      guinea-pig isolated airways.
AB  - The mediators of bronchoconstriction of isolated lungs and trachea from ovalbumen
      sensitized guinea-pigs to adenosine and ovalbumen were examined using relevant
      antagonists. Changes in perfusion pressure and tension of paired lung halves and
      tracheal spiral strips, respectively, were recorded in response to adenosine (1
      mM lung, 300 microM trachea), histamine (10 microM), methacholine (10 microM) and
      ovalbumen (10 microg). One half was perfused with antagonist while the other
      received vehicle. Tracheal strips were superfused throughout with the P(1)
      receptor antagonist 8-phenyltheophylline, to examine 8-phenyltheophylline
      resistant responses. The histamine H(1) receptor antagonist, mepyramine (1.5 mM),
      the cyclooxygenase inhibitors, indomethacin (5 mM) and diclofenac (5 mM), the
      leukotriene receptor antagonist, zafirlukast (1 mM), and the lipoxygenase
      inhibitor, zileuton (20 mM), alone failed to inhibit bronchoconstriction by
      adenosine and ovalbumen of the lung and trachea. When two antagonists were
      combined, only mepyramine and zafirlukast significantly reduced the lung
      responses to adenosine and ovalbumen. The tracheal adenosine response was
      substantially reduced, although not significantly, while ovalbumen was
      significantly reduced. When mepyramine, indomethacin and zafirlukast were
      combined, the lung constriction by adenosine and ovalbumen were virtually
      abolished. Similarly, the combination of mepyramine, diclofenac and zafirlukast
      significantly attenuated the lung responses to adenosine and ovalbumen. Thus,
      histamine, cyclooxygenase products and leukotrienes alone are not responsible for
      the bronchoconstriction of isolated sensitized lung tissues to adenosine or
      ovalbumen, which appears to be due to the release of all three mediators.

PMID- 12223234
TI  - Involvement of Raf-1 in chronic delta-opioid receptor agonist-mediated adenylyl
      cyclase superactivation.
AB  - Chronic delta-opioid receptor agonist treatment of Chinese hamster ovary (CHO)
      cells stably expressing the human delta-opioid receptor (hDOR/CHO) leads to
      increased cAMP formation after the removal of the agonist (adenylyl cyclase
      superactivation). We have previously found that at the same time, chronic delta
      opioid receptor agonist treatment augments phosphorylation of the adenylyl
      cyclase VI isoenzyme. Since phosphorylation of adenylyl cyclase VI by Raf-1
      protein kinase was recently shown, we tested the role of Raf-1 in adenylyl
      cyclase superactivation in hDOR/CHO cells. We found that pretreatment of the
      cells with the selective Raf-1 inhibitor GW5074 (3-(3,5-dibromo-4
      hydroxybenzylidene-5-iodo-1,3-dihydro-indol-2-one) (10 microM, 30 min) attenuates
      chronic deltorphin II-mediated increase in forskolin-stimulated cAMP formation by
      40% (n = 6, P < 0.05). Better understanding of the molecular mechanism of
      adenylyl cyclase superactivation should aid in the development of analgesics that
      act longer and have fewer side effects.

PMID- 12223235
TI  - Different ways to insert carotenoids into liposomes affect structure and dynamics
      of the bilayer differently.
AB  - We apply and quantify two techniques to incorporate carotenoids into liposomes:
      (i). preparation of unilamellar liposomes from mixtures of phospholipids and a
      carotenoid or cholesterol; (ii). insertion of carotenoids into prepared
      liposomes. Homogeneous liposomal fractions with a vesicle size diameter of
      approximately 50 nm were obtained by an extrusion method. The resulting vesicles
      were subjected to a three-dimensional light scattering cross-correlation
      measurement in order to evaluate their size distribution. The fluorescent dyes
      Laurdan, DiI-C(18), C(6)-NBD-PC were used to label the liposomes and to evaluate
      modulations of ordering, hydrophobicity and permeability to water molecules
      adjacent to the bilayer in the presence of carotenoids and/or cholesterol.
      Zeaxanthin incorporation (up to 0.1-1 mol%) attributes to the symmetric and
      ordered structure of the bilayer, causing both a strong hydrophobicity and a
      lower water permeability at the polar region of the membrane. The incorporation
      of lutein has similar effects, but its ordering effect is inferior in the polar
      region and superior in the non-polar region of the membrane. beta-Carotene, which
      can be incorporated at lower effective concentrations only, distributes in a more
      disordered way in the membrane, but locates preferentially in the non-polar
      region and, compared to lutein and zeaxanthin, it induces a less ordered
      structure, a higher hydrophobicity and a lower water permeability on the bilayer.

PMID- 12223237
TI  - Antibody/antigen affinity behavior in liquid environment with electrical
      impedance analysis of quartz crystal microbalances.
AB  - Electrical impedance analysis has been used to study anti-human immunoglobulin G
      (anti-h IgG) adsorption and the subsequent human immunoglobulin G (hIgG) or
      rabbit immunoglobulin G (rIgG) affinity reaction in aqueous liquids on a
      polystyrene (PS)-modified quartz crystal microbalance (QCM) surface. Time
      dependent adsorption data of both the frequency shift and the electrical
      equivalent parameters (motional resistance, shunt capacitance, quality factor,
      etc) are monitored. It was found that the motional resistance, R, increases while
      the resonance frequency, f, decreases during both the anti-h IgG immobilization
      and the subsequent affinity process. Decreasing f primarily arises from the
      increased mass loading. Increasing R indicates more power dissipation (increased
      losses) in the system. The change in motional resistance, delta R, in the
      affinity reaction is considerably larger than that in anti-h IgG immobilization
      adsorption process, although the resonant frequency shifts, delta f, are very
      close in these two processes. Specifically, for a saturated solution, the ratio
      of delta R/delta f is 9.45 x 10 (-3) Omega/Hz for anti-h IgG adsorption and 28.1
      x 10 (-3) omega/Hz for anti-h IgG/hIgG binding respectively, indicating the
      increased power dissipation with the increasing binding molecules. The shunt
      capacitance changes little in the hIgG binding process ( approximately 0.01 pF).

PMID- 12223236
TI  - Spectroscopic analysis of low pH and lipid-induced structural changes in type A
      botulinum neurotoxin relevant to membrane channel formation and translocation.
AB  - Botulinum neurotoxin (BoNT) is an extremely toxic protein to animals and humans.
      In its mode of action, one of its subunits mediates its translocation by
      integrating itself into the membrane bilayer. We have examined the membrane
      channel activity of type A BoNT (BoNT/A) and its heavy (H) chain in planar lipid
      membrane under various pH conditions to understand the possible role of the
      channel activity in the translocation of the BoNT/A light (L) chain under
      physiological conditions. Only BoNT/A H chain, and not the BoNT/A, exhibited
      membrane channel activity for translocation of ions. The H chain-induced increase
      in conductance did not require a pH gradient across the lipid membrane, although
      it was enhanced by a pH gradient. To understand the molecular basis of the
      membrane channel activity and the translocation of the L chain, the secondary
      structure of BoNT/A and its H and L chains were analyzed using circular dichroism
      (CD) and Fourier-transform infrared (FT-IR) spectroscopy at different pH values.
      BoNT/A showed no structural alternation upon acidifying the buffer pH. However,
      an increase in beta-sheet content of BoNT/A H chain at low pH was noted when
      examined by FT-IR. The L chain structure significantly changed with decrease in
      pH, and the change was mostly reversible. In addition, the neurotoxin and its
      subunit chains induced a partially reversible aggregation of liposomes at low pH,
      which indicated their integration into the lipid bilayer. Temperature-induced
      denaturation studies of BoNT/A H chain indicated major structural reorganization
      upon its interaction with membrane, especially at low pH.

PMID- 12223238
TI  - Proton concentration (pH) switches the higher-order structure of DNA in the
      presence of spermine.
AB  - Single-chain observations on the conformational change of giant DNA (T4 DNA)
      molecules were performed using fluorescence microscopy at different values of pH
      in the presence of spermine. Individual DNA molecules undergo a large discrete
      change, or all-or-none transition, in conformation from a folded compact state to
      an unfolded coil state with an increase in pH. This abrupt unfolding of DNA with
      an increase in pH is attributed to a decrease in the concentration of the
      tetravalent form in spermine [SPM(4+)]. We propose a scheme for the folding
      transition of single DNAs, where the manner of spermine binding changes
      dramatically from weak loose binding in the elongated coil state to strong tight
      binding in the folded compact state. We discuss the hierarchical nature of the
      transition, i.e. cooperative continuous change on the ensemble vs. all-or-none
      switching on individual DNAs.

PMID- 12223239
TI  - ZL-DHP lignin model compound at the air-water interface.
AB  - In this paper we present our surface chemistry studies of enzymatically
      polymerized, poly-coniferyl alcohol lignin model compound (dehydrogenate polymer
      a.k.a. ZL-DHP) at the air-water interface. Using the CHCl(3)/MeOH (5:1 v/v)
      spreading solvent, we found an average molecular area of ZL-DHP of approximately
      1200 A(2). The monolayer expresses a high compressibility with a collapsed area
      of 500 A(2) and collapsed surface pressure of 28 mN m(-1). In the range of
      applied surface pressures, ZL-DHP polymer have no phase changes, as shown by the
      very high linearity (R=0.994) of absorbance vs. surface pressure cure. There was
      no symmetry transitions observed as shown by absence of shifts of absorption peak
      maximums.

PMID- 12223240
TI  - Treatment of multifunctional enzymes in metabolic pathway analysis.
AB  - In metabolic pathway analysis, it should be considered that many enzymes operate
      with low specificity (e.g. nucleoside diphosphokinase, uridine kinase,
      transketolase, aldolase), so that various substrates and products can be
      converted. Here, we analyze the effect of enzymes with low substrate specificity
      on the elementary flux modes (pathways). We also study the benefits of two
      different approaches to describing multifunctional enzymes. The usual description
      is in terms of (overall) enzymatic reactions. At a more detailed level, the
      reaction steps (half-reactions, hemi-reactions) of the formation and conversion
      of enzyme-substrate complexes are considered. Multifunctional enzymes operate
      according to various mechanisms. This is illustrated here by the reaction schemes
      for the different enzyme mechanisms of bifunctional enzymes. For enzymes with two
      or more functions, it is important to consider only linearly independent
      functions, because otherwise cyclic elementary modes would occur which do not
      perform any net transformation. However, the choice of linearly independent
      functions is not a priori unique. We give a method for making this choice unique
      by considering the extreme pathways of the hemi-reactions system. A formal
      application of the algorithm for computing elementary flux modes (pathways)
      yields the result that the number of such modes sometimes depend on the level of
      description if some reactions are reversible and the products of the
      multifunctional enzymes are external metabolites or some multifunctional enzymes
      partly share the same metabolites. However, this problem can be solved by
      appropriate interpretation of the definition of elementary modes and the correct
      choice of independent functions of multifunctional enzymes. The analysis is
      illustrated by a biochemical example taken from nucleotide metabolism, comparing
      the two ways of description for nucleoside diphosphokinase and adenylate kinase,
      and by several smaller examples.

PMID- 12223241
TI  - Analysis of DNA curvature distribution in mycobacterial promoters using
      theoretical models.
AB  - In this paper, 125 different mycobacterial promoters are analyzed for their DNA
      curvature distribution using several di- and tri-nucleotide dependent models of
      DNA curvature. Different models give similar behavior and therefore qualitative
      validation of the results. Mycobacterial promoters resembling the E. coli
      sigma(70) type have almost 81% (85%) sequences having medium and high curvature
      profiles using dinucleotide-dependent models. Non-E. coli sigma(70) type
      mycobacterial promoters have comparatively higher percent of low curvature
      profiles. Very few extended -10 promoters have low curvature profiles.
      Mycobacterial promoters having A(n)T(m) (n+m > or =3) tract in the upstream
      region of -35 box and repeated in phase with each other have high curvature
      profiles. M. smegmatis promoters have high curvature profiles compared to M.
      tuberculosis promoters.

PMID- 12223242
TI  - Interaction of low-molecular-weight chitosan with mimic membrane studied by
      electrochemical methods and surface plasmon resonance.
AB  - Chitosan has shown its potential as a non-viral gene carrier and an adsorption
      enhancer for subsequent drug delivery to cells. These results showed that
      chitosan acted as a membrane perturbant. However, there is currently a lack of
      direct experimental evidence of this membrane perturbance effect, especially for
      chitosans with low molecular weight (LMW). In this report, the interaction
      between a lipid (didodecyl dimethylammonium bromide; DDAB) bilayer and chitosan
      with molecular weight (MW) of 4200 Da was studied with cyclic voltammetry (CV),
      electrochemical impedance spectroscopy and surface plasmon resonance (SPR). A
      lipid bilayer was formed by fusion of oppositely charged lipid vesicles on a
      mercaptopropionic acid (MPA)-modified gold surface to mimic a cell membrane. The
      results showed that the LMW chitosan could disrupt the lipid bilayer, and the
      effect seemed to be in a concentration-dependent manner.

PMID- 12223243
TI  - Layer-specific reductions in GFAP-reactive astroglia in the dorsolateral
      prefrontal cortex in schizophrenia.
AB  - Neuroimaging studies have implicated the prefronto-striatal loop as a substrate
      for the cognitive deficits in schizophrenia (SCHZ). Postmortem morphometric
      studies reveal that layers III and V of the dorsolateral prefrontal cortex
      (dlPFC), which gave rise to glutamatergic projections to neostriatum, demonstrate
      the most structural pathology in this region of the SCHZ. These neuronal
      alterations in SCHZ are not accompanied by marked glial changes as revealed by
      Nissl staining. We examined the glial-type specific pathology in SCHZ by
      analyzing the glial fibrillary acidic protein- (GFAP) immunoreactive astroglia in
      contrast to the Nissl-stained general pool of glial cells in dlPFC (area 9) from
      9 subjects with SCHZ and 15 psychiatrically normal control subjects. In layer V
      of the dlPFC in SCHZ, there was a significant 32% reduction in the GFAP-area
      fraction, 81% increase in the density of the GFAP-positive cell bodies and a 14%
      decrease in the width of the cortical layer V, as compared to the control
      subjects. None of these parameters were affected in layers III and IV in the
      SCHZ. Therefore, only subtle, type- and layer-specific glial pathology is present
      in the dlPFC in SCHZ. Astroglial pathology in dlPFC may reflect disturbances of
      the neuron-glia interactions in layer V and may be related to the dysfunctional
      prefronto-striatal circuits, dopaminergic alterations and cognitive pathology in
      SCHZ.

PMID- 12223244
TI  - The association between schizophrenia and cancer: a population-based mortality
      study.
AB  - BACKGROUND: For most of this century there has been speculation that persons
      diagnosed with schizophrenia have a reduced incidence of cancer. OBJECTIVE: To
      determine if a history of cancer was more common in persons diagnosed with
      schizophrenia when compared with the general population, controlling for known
      risk and demographic factors. DESIGN: We used the 1986 National Mortality
      Followback Survey (NMFS) which sampled 1% of all deaths in the US from that year.
      Data were obtained from death certificates and records of hospitalizations in the
      last year of life. Additional health and demographic data were obtained through
      interviews with decedents' families and other informants. We compared persons
      diagnosed with schizophrenia (n=130) to individuals without schizophrenia
      (n=18,603) and used logistic regression to determine the odds ratio for the
      occurrence of cancer in persons diagnosed with schizophrenia. Adjustment for age
      at death was done to correct for the fact that persons diagnosed with
      schizophrenia die on average 10 years younger than the general population. MAIN
      OUTCOME MEASURE: A diagnosis of cancer on a hospital record or the death
      certificate. RESULTS: The unadjusted odds ratio for cancer among individuals with
      schizophrenia was 0.62 (95% confidence interval (CI) 0.40-0.96). After
      controlling for age, race, gender, marital status, education, net worth, smoking,
      and hospitalization in the year before death, we determined that the odds ratio
      for the diagnosis of cancer in persons with schizophrenia was 0.59 (95% CI 0.38
      0.93). CONCLUSION: In this population-based study, we demonstrated a reduced risk
      of cancer among persons diagnosed with schizophrenia.

PMID- 12223245
TI  - Neuroleptics and mortality in schizophrenia: prospective analysis of deaths in a
      French cohort of schizophrenic patients.
AB  - OBJECTIVE: The putative role of neuroleptics in the known excess mortality of
      subjects with schizophrenia remains disputed. The aim of this study was to assess
      the link between mortality and the class of neuroleptic. METHOD: Causes of death
      (suicide, cardiovascular, etc.) and exposure to neuroleptics were studied in a
      cohort of 3474 patients with schizophrenia followed from 1993 to 1997. RESULTS:
      From 1993 to 1997, 178 patients died. The risk of all-cause death (OR=1.59; 95%
      CI 1.02-2.50; p=0.04), and suicide (OR=2.22; 95% CI 1.24-3.97; p=0.006) were
      increased in users of thioxanthenes (alone or associated with other drugs), and
      increased risk of "other causes" of death was associated with use of atypical
      neuroleptics (OR=2.06; 95% CI 1.15-3.70; p=0.0016). CONCLUSION: Our findings
      suggest the existence of association between certain classes of neuroleptics and
      death, all cause or specific. This could be related to the drug itself or to
      patient selection.

PMID- 12223246
TI  - Seasonal fluctuation in birthweight in schizophrenia.
AB  - The birthweights of 450 schizophrenic patients born in 1971-1978 were compared
      with those of individually matched controls from the same birth cohort.
      Schizophrenics born in the second quarter of the year (April to June) had a
      significantly lower birthweight than their controls and this was not attributable
      to differences in the duration of gestation. Analogous proband/control
      differences were not found in 301 patients with affective psychoses, but there
      was a similar, much smaller, seasonal fluctuation in birthweight in the general
      population. These findings may be a clue both to the genesis of the "season of
      birth effect" and to the identity of the intrauterine influences contributing to
      the aetiology of schizophrenia. Folate deficiency may be implicated.

PMID- 12223247
TI  - Remediation of problem-solving skills in schizophrenia: evidence of a persistent
      effect.
AB  - Neuropsychological deficits in problem solving are commonly found in patients
      with schizophrenia. We have previously presented the results of a study examining
      the feasibility of utilizing problem-solving teaching techniques developed within
      educational psychology, for remediating the problem-solving deficits of
      inpatients with schizophrenia spectrum disorders. These techniques emphasize the
      importance of intrinsic motivation on therapeutic outcome and promote this
      through contextualization, personalization and control of learning activities. We
      present here the results of the follow-up assessment, which found that the gains
      made by the problem-solving group persisted for 4 weeks after cessation of
      problem-solving remediation ended. These results provide more evidence of the
      therapeutic benefit of problem-solving training techniques that promote intrinsic
      motivation and generic problem-solving strategies.

PMID- 12223248
TI  - Wisconsin Card Sorting deficits in the offspring of schizophrenics in the New
      York High-Risk Project.
AB  - It has been suggested that performance on the Wisconsin Card Sorting Test (WCST)
      may be an indicator of vulnerability to schizophrenia. WCST deficits have been
      demonstrated in schizophrenic patients and their relatives, but not as yet in
      their offspring. This study aimed to further establish the indicator potential of
      WCST deficits by analyzing data collected as part of the New York High-Risk
      Project (NYHRP), a longitudinal study of attention, cognition and clinical
      functioning in the offspring of schizophrenic (HRSz, n=73), affective disordered
      (HRAff, n=61) and normal comparison (NC, n=120) parents. Parental Research
      Diagnostic Criteria diagnoses were established by semi-structured interview (SADS
      L). WCST testing was carried out when offspring were in their mid-20s. HRSz
      subjects performed significantly more poorly on the WCST than HRAff and NC
      subjects. High-risk subjects who developed psychotic symptoms prior to or shortly
      after testing did not differ significantly from HRSz subjects who did not become
      ill. Thus, WCST performance in the offspring of schizophrenics resembles that of
      schizophrenic patients and may distinguish HRSz from offspring at risk for
      nonschizophrenic illness. WCST deficits may be a specific familial indicator of
      vulnerability, but appear not to distinguish between those subjects at risk for
      schizophrenia who do or do not become ill.

PMID- 12223249
TI  - The course of parental expressed emotion and psychotic episodes after family
      intervention in recent-onset schizophrenia. A longitudinal study.
AB  - The stability of parental expressed emotion (EE) is analysed over about 9 years,
      and related to course of illness in patients with recent-onset schizophrenia.
      Families, who participated in a 15-month intervention, were randomised over two
      intervention conditions. Psychotic episodes were measured over 5 years after
      discharge. The Five Minute Speech Sample (FMSS) EE was elicited two times during
      the 12-month outpatient intervention and two times over 8 years after discharge
      on average. EE is expressed as criticism/dissatisfaction (CRIT), emotional
      overinvolvement (EOI), and as the classical dichotomous index. EE is not stable
      over the years. Intervention condition had no differential effect on EE as
      measured with CRIT and the dichotomous index. For EOI, an interaction between
      intervention condition and time was found. EE as assessed during intervention
      does not predict psychotic episodes during follow-up. An association was found
      between psychotic episodes and CRIT as assessed at 34 months after discharge.
      Family intervention may inhibit the development of high EOI for a limited period.
      Our results may be in support of the hypothesis that psychotic episodes in
      patients can affect the critical attitude in parents.

PMID- 12223250
TI  - Gender differences in living with schizophrenia. A cross-sectional European multi
      site study.
AB  - The EPSILON project (European Psychistric Services: Inputs Linked to Outcomes and
      Needs) is a cross-sectional study of the clinical and social characteristics,
      needs, satisfaction with services, quality of life, and service utilisation and
      costs for people with schizophrenia in five European sites (Amsterdam,
      Copenhagen, London, Santander, and Verona). This study examined five hypotheses:
      (1) Men will have more total needs and more unmet needs for: 'accommodation',
      'substance misuse', 'psychotic symptoms', 'harm to others', and 'sexual
      expression', whereas women will have more total needs and more unmet needs in the
      domains of 'childcare' and 'harm to self'. (2) Caregivers of male patients will
      show higher rates of psychological distress, and higher scores for 'supervision'
      and 'urging' than caregivers of female patients. (3) Male and female patients
      will show similar levels of satisfaction with services, both in total scores and
      subscores. (4) Male patients will show lower objective quality of life, but
      similar subjective quality of life compared with women. (5) Service utilization
      for men and women will differ, and patterns will vary by site. The results
      confirmed hypotheses 1 (in part) and 3, but failed to support hypotheses 2, 4 and
      5. Graphical models were used to generate hypotheses for future research. The
      implications for planning separate services for male and female schizophrenic
      patients are discussed.

PMID- 12223251
TI  - Switching from conventional to novel antipsychotic drugs: results of a
      prospective naturalistic study.
AB  - OBJECTIVE: We examined the long-term consequences of switching patients from
      conventional to novel antipsychotic drugs, from a patient's perspective. METHODS:
      In a prospective, single-blinded, naturalistic study, a cohort of subjects
      (n=150) with schizophrenia or schizo-affective disorder (DSM-IV) were switched
      from conventional neuroleptic drugs to either risperidone (n=50), olanzepine
      (n=50) or quetiapine (n=50), and monitored for a period of 2 to 6 years. The
      ensuing natural history of transitions in treatments was charted, and the
      outcomes including symptoms, side effects, subjective tolerability of drugs and
      their impact on quality of life were documented with standardized rating scales.
      RESULTS: Majority (85%) of the subjects benefited from a switch to the novel
      antipsychotic drugs, though some preferred to return to their original
      neuroleptic (8%), and others eventually required clozapine (7%) therapy. Novel
      antipsychotic drugs were significantly tolerated better, and had a positive
      impact on treatment-adherence, psychosocial functioning and quality of life.
      Among the novel drugs, risperidone was significantly better in improving negative
      symptoms, while olanzepine was particularly well tolerated and effective against
      comorbid anxiety and depressive symptoms. Patients treated with quetiapine
      reported fewer side effects, and showed a significantly greater improvement in
      neurocognitive deficits. CONCLUSION: Novel antipsychotics emerged as the drug of
      choice in view of their overall effectiveness, though conventional neuroleptics
      and clozapine will continue to have a limited but distinct role in the management
      of schizophrenia. The challenge for clinicians lies in matching a patient's
      clinical and biochemical profile with that of a drug's pharmacological actions,
      in order to achieve optimum outcomes.

PMID- 12223252
TI  - Predictors of medication discontinuation by patients with first-episode
      schizophrenia and schizoaffective disorder.
AB  - BACKGROUND: Enhancing medication adherence early in the course of schizophrenia
      and schizoaffective disorder may substantially improve long-term course. Although
      extensively studied in multi-episode patients, little data exist on medication
      adherence by first-episode patients. METHOD: Medication adherence was assessed
      during the first year of treatment and following recovery from the first relapse
      in patients treated by a standardized medication algorithm. RESULTS: During the
      first year of treatment, patients with poorer premorbid cognitive functioning
      were more likely to stop antipsychotics (t=-2.54, df=75, p=0.01). Parkinsonian
      side effects increased the likelihood (hazard ratio=41.22; 95% CI=2.30, 737.89;
      p=0.01), and better executive function decreased the likelihood (hazard
      ratio=0.40; 95% CI=0.18, 0.88; p=0.02) that patients discontinued maintenance
      medication after a first relapse. CONCLUSION: Interventions to ameliorate
      cognitive deficits and Parkinsonian side effects may enhance treatment adherence.

PMID- 12223253
TI  - Preliminary experience with an ampakine (CX516) as a single agent for the
      treatment of schizophrenia: a case series.
AB  - We used L-(quinoxalin-6-ylcarbonyl)piperidine (CX516) (a modulator of the alpha
      amino-3-hydroxy-5-methyl-4-isoxasole propionic acid (AMPA) receptor) as a sole
      agent in a double blind placebo-controlled design in a small series of patients
      with schizophrenia who were partially refractory to treatment with traditional
      neuroleptics. The study entailed weekly increments in doses of CX516, from 300 mg
      tid for week 1 up to 900 mg tid on week 4. Patients were followed with clinical
      ratings, neuropsychological testing, and were monitored for adverse events. Four
      patients received 2 to 4 weeks of CX516, two received placebo and two withdrew
      during the placebo phase. Adverse events associated with drug administration were
      transient and included leukopenia in one patient and elevation in liver enzymes
      in another. No clear improvement in psychosis or in cognition was observed over
      the course of the study. CX516 at the doses tested did not appear to yield
      dramatic effects as a sole agent, but inference from this study is limited.

PMID- 12223254
TI  - Extrapyramidal symptom profiles in Japanese patients with schizophrenia treated
      with olanzapine or haloperidol.
AB  - Previous clinical trials have clearly shown the superiority of olanzapine to
      haloperidol in the improvement of extrapyramidal symptoms (EPS) in schizophrenic
      patients. The primary purpose of this study was to compare EPS profiles in
      Japanese schizophrenic patients treated with an atypical antipsychotic,
      olanzapine, or a typical antipsychotic, haloperidol, as measured by the Drug
      Induced Extrapyramidal Symptoms Scale (DIEPSS). The DIEPSS, which consists of
      eight individual parameters and one global assessment (overall severity), was
      used to evaluate 182 patients enrolled in this 8-week study. The primary safety
      analysis was maximum change (that could be either a decrease or increase) from
      baseline in DIEPSS total score. Secondary analyses included change from baseline
      to maximum in DIEPSS total score, change from baseline to endpoint (LOCF) in
      DIEPSS total score, and the rank sum of the maximum change (that could be either
      a decrease or increase) from baseline in the DIEPSS individual items. Incidence
      of treatment-emergent EPS adverse events using the DIEPSS scale was also
      analyzed. The olanzapine group showed statistically significant superiority to
      the haloperidol group on the primary analysis (p<0.001). Secondary analyses also
      demonstrated olanzapine's superiority in DIEPSS total, parkinsonism, akathisia
      and overall severity scores (all p< or =0.014). Categorical analysis of treatment
      emergent akathisia and parkinsonism syndromes at endpoint showed improvement in
      the olanzapine group but worsening in the haloperidol group. The results from
      this study suggest that olanzapine, as in Caucasian populations, is a safe
      treatment in Japanese patients chronically ill with schizophrenia.

PMID- 12223255
TI  - Ethnic heterogeneity in allele variation in the DRD4 gene in schizophrenia.
AB  - The goal of the present study was to use a meta-analysis on previous studies plus
      our own unpublished data to confirm and extend findings which indicate that the
      variation in the dopamine D4 receptor (DRD4) gene is best represented by a
      mixture of two different ethnic groups. The genotype distribution was divided
      into either a long or short form using a mixture analysis of normal controls of
      different ethnic origins under the assumption that there is a single major gene.
      The meta-analysis was based on the data from 19 independent samples, 18
      association studies, and from our own unpublished data, including a total of 1431
      schizophrenic patients (sporadic cases 1309, familial cases 122) and 1439
      controls. No significant genotype differences were noted between patients and
      controls for the whole sample. However, reorganization of the studies into
      different groups by the geographical origin of samples revealed significant
      ethnic heterogeneity. In addition, there was a significant association between
      the long form of DRD4 gene and schizophrenia in Caucasians, especially those with
      familial schizophrenia.

PMID- 12223256
TI  - Elevated interleukin-2, interleukin-6 and interleukin-8 serum levels in
      neuroleptic-free schizophrenia: association with psychopathology.
AB  - Cytokines have been one of the recent focal points of immunological research in
      schizophrenia. The present study was to assess the serum levels of some of
      interleukins in schizophrenia and their relationships with the psychopathological
      parameters. Seventy physically healthy Chinese patients, who met DSM-III-R
      criteria for schizophrenia and who were drug-free for at least 2 weeks, were
      compared with 30 age- and sex-matched Chinese normal controls. The
      psychopathology of schizophrenia was assessed by the Positive and Negative
      Syndrome Scale (PANSS). Serum levels of IL-6 and IL-8 were measured by sandwich
      enzyme-linked immunosorbent assay (ELISA), and serum IL-2 level was assayed by
      radioimmunometric assay (RIA). Serum levels of IL-2, IL-6 and IL-8 were
      significantly elevated in patients with a chronic form of schizophrenia (all
      p<0.05). There was a significant inverse relationship between IL-2 level and the
      PANSS positive subscale P (r=-0.31, p=0.006) and a significant positive
      correlation between IL-8 level and PANSS negative subscale N (r=0.25, p=0.036) in
      schizophrenic patients. In control subjects, a significant and positive
      relationship between serum IL-2 and IL-6 (r=0.513, p=0.004) was noted, whereas,
      there was a significant and negative relationship between IL-2 and IL-8 in
      schizophrenic patients (r=-0.28, p=0.02). Our data confirms and supports the view
      that immune disturbance is involved in schizophrenia, which is compatible with
      the possibility that Chinese schizophrenic patients have an ongoing autoimmune
      process. This immune disturbance is related to the subgroup of schizophrenic
      patients with characteristic clinical variables. The dysfunction of interaction
      or inter-adjustment between different cytokines may exist in schizophrenic
      patients.

PMID- 12223257
TI  - The dichotomy of schizophrenia and affective disorders in extended pedigrees.
AB  - The paper reports the first controlled family study investigating not only 1st
      but also 2nd and 3rd degree relatives of patients with schizophrenia by direct
      diagnostic interviews. Regardless of their degree of relationship, all biological
      relatives of the patients were found to be at an elevated risk of schizophrenia
      (5.0% in 1st, 3.1% in 2nd, 1.5% in 3rd degree relatives compared to 0.8% among
      controls). Schizoaffective and affective disorders have also been found to be
      more common in the three groups of relatives but without a monotone decline of
      prevalence rates across the groups. Other psychiatric disorders were not found to
      be at an elevated risk in relatives of patients compared to controls. Thus, our
      findings support the hypothesis that psychotic, as well as affective disorders,
      aggregate in families of individuals with schizophrenia.However, in our study,
      the risk of schizophrenia and the risk of affective disorders correlated.
      Particularly, the magnitude of the risk of schizophrenia among relatives of
      probands with schizophrenia varied with the occurrence of affective disorders in
      relatives. In relatives, the risk of schizophrenia was maximal in absence of a
      family history of affective disorder. This constellation holds true even if only
      families of index cases without any affective syndrome during lifetime are
      considered.

PMID- 12223258
TI  - Analysis of ependymal abnormalities in subjects with schizophrenia, bipolar
      disorder, and depression.
AB  - Abnormalities of the ependyma can serve as a marker of early brain insults. The
      presence of ependymal abnormalities was determined in sections containing
      ependyma of the temporal horn obtained from the Stanley Neuropathology
      Consortium: 15 subjects with schizophrenia, 15 with bipolar illness, 15 with
      major depression and 15 normal controls. There were no significant differences in
      numbers of subjects with ependymal discontinuities or subventricular rosettes.
      Subjects with schizophrenia had significantly less nodular gliosis than normal
      subjects (p=0.02); there was a trend for subjects with depression to have less
      nodular gliosis than normal subjects (p=0.06). Control subjects had unexpectedly
      high rates of ependymal abnormalities, indicating that ependymal abnormalities
      may not be a useful marker of pre- or perinatal events associated with
      schizophrenia and other psychiatric disorders in adult postmortem tissue.

PMID- 12223259
TI  - Neural damage in the lenticular nucleus linked with tardive dyskinesia in
      schizophrenia: a preliminary study using proton magnetic resonance spectroscopy.
AB  - We investigated, using proton magnetic resonance spectroscopy (1H-MRS), whether
      the tardive dyskinesia (TD) often seen in schizophrenic patients is associated
      with cellular abnormalities in the basal ganglia system. The subjects in this
      study included schizophrenic patients with TD (TD group, n=7), schizophrenic
      patients without TD (non-TD group, n=7), and healthy volunteers (N group, n=7).
      We examined the 1H-MRS peaks of N-acetylaspartate (NAA), choline (Cho), and
      creatine (Cr) in the regions of the left and right lenticular nucleus. In the
      left lenticular nucleus, the Cho/Cr ratio was significantly greater in the TD and
      non-TD groups than in the N group (Mann-Whitney U test; p<0.007 and p<0.006,
      respectively). Further, a significant linear trend was observed in the means of
      the ratio across the three groups (p<0.005); the TD group was the highest, the N
      group the lowest, and the non-TD group intermediate. No significant difference in
      the NAA/Cr ratio was found among groups. These results indicate that neural
      abnormalities in the basal ganglia may be linked with the neuroleptic medications
      and the process of the fundamental illness per se, and that more excessive damage
      to this neural substrate may lead to development of TD. However, as this is a
      preliminary study, further studies with a large number of subjects are required
      to verify our findings.

PMID- 12223261
TI  - Polydipsia and schizophrenia in a psychiatric hospital: a replication study.
AB  - A prior study in a US state hospital suggested that schizophrenia, smoking and
      long hospitalization were associated with polydipsia. This study, in another US
      hospital, attempts to (1) replicate that schizophrenia and smoking are associated
      with polydipsia, and (2) rule out that this relationship is partly explained by
      alcohol and drug use. Both studies have similar methodologies. The second sample
      included 588 inpatients. Models of variables associated with polydipsia were
      developed using logistic regression. In the second study, after correcting for
      other factors, the association between polydipsia and schizophrenia showed a
      borderline significance, while polydipsia and smoking displayed a significant
      association. Neither organic brain lesions, nor alcohol or drug use, were
      associated with polydipsia. An analysis combining both samples showed that: (1)
      schizophrenia, long hospitalization, smoking and heavy smoking were significantly
      associated with polydipsia, and (2) male gender and Caucasian race (but not
      smoking) increased the risk of developing water intoxication in polydipsic
      patients. These two studies in severely mentally ill patients suggest that the
      association of polydipsia with schizophrenia, smoking and chronicity is
      consistent and independent from the definition of polydipsia (by staff, a
      biological method or the combination of both). Psychiatric medications do not
      appear to explain most cases of polydipsia in these patients.

PMID- 12223260
TI  - Clinical signs of cerebellar dysfunction in schizophrenia, alcoholism, and their
      comorbidity.
AB  - Abnormalities of cerebellar structure and function, long recognized as a hallmark
      of chronic alcohol abuse, have also occasionally been noted in patients with
      schizophrenia. We used a four-point rating scale to assess clinical signs of
      cerebellar dysfunction in men meeting DSM-IV criteria for schizophrenia (N=34)
      and alcohol dependence (N=15) as well as normal control subjects (N=28). Compared
      to controls, alcoholics had impaired ratings of gait ataxia and instability of
      stance with eyes closed, and schizophrenics had impaired ratings of stance with
      eyes closed. The incidence of dysdiadochokinesia was greater in schizophrenics,
      but not alcoholics, than controls. The incidence of gait and stance abnormalities
      was higher in both patient groups relative to controls: within the schizophrenic
      group, 50-70% of those with positive signs for gait or stance impairment were
      comorbid for alcoholism, while only 25% of those with positive signs for
      dysdiadochokinesia were comorbid for alcoholism. The presence of
      dysdiadochokinesia in the schizophrenic group suggests cerebellar dysfunction
      that is independent of the effects of alcohol. By contrast, clinical signs of
      cerebellar dysfunction of gait and stance in patients with schizophrenia may be
      secondary to the effects of alcohol on the cerebellum.

PMID- 12223262
TI  - Borna disease virus and psychiatric disorders.

PMID- 12223263
TI  - Overlap between emotional blunting, depression, and extrapyramidal symptoms in
      schizophrenia.

PMID- 12223264
TI  - Effect of zotepine, olanzapine and risperidone on hostility in schizophrenic
      patients.

PMID- 12223265
TI  - Hallucinations in schizophrenia: imbalance between imagery and perception?

PMID- 12223267
TI  - The sugar code: functional lectinomics.
AB  - Analysis of the genome and proteome assumes the focus of attention in efforts to
      relate biochemical coding with cell functionality. Among other chores in energy
      metabolism, the talents of carbohydrates to establish a high-density coding
      system give reason for a paradigmatic shift. The sequence complexity of glycans
      and glycan-processing enzymes (glycosyltransferases, glycosidases and enzymes
      introducing substituents such as sulfotransferases), the growing evidence for the
      importance of glycans from transgenic and knock-out animal models and the
      correlation of defects in glycosylation with diseases are substantial assets to
      portray oligosaccharides as code words in their own right. Matching the pace of
      progress in the work on glycoconjugates, the increasing level of refinement of
      our knowledge about lectins (definition of this term: carbohydrate-binding
      proteins, excluding sugar-specific antibodies, receptors of free mono- or
      disaccharides for transport or chemotaxis and enzymes modifying the bound
      carbohydrate) epitomizes the sphere of action of the sugar code (functional
      lectinomics). It encompasses, among other activities, intra- and intercellular
      transport processes, sensor branches of innate immunity, regulation of cell-cell
      (matrix) adhesion or migration and positive/negative growth control with
      implications for differentiation and malignancy. The Q & A approach taken in this
      review lists a series of arguments in a stepwise manner to make the reader wonder
      why it is only a rather recent process that the concept of the sugar code has
      taken root in deciphering the mechanistic versatility of biological information
      storage and transfer.

PMID- 12223268
TI  - Chemical biology of dynamic combinatorial libraries.
AB  - Dynamic combinatorial chemistry (DCC) is a recently introduced supramolecular
      approach to generate libraries of chemical compounds based on reversible exchange
      processes. The building elements are spontaneously and reversibly assembled to
      virtually encompass all possible combinations, allowing for simple one-step
      generation of complex libraries. The method has been applied to a variety of
      combinatorial systems, ranging from synthetic models to materials science and
      drug discovery, and enables the establishment of adaptive processes due to the
      dynamic interchange of the library constituents and its evolution toward the best
      fit to the target. In particular, it has the potential to become a useful tool in
      the direct screening of ligands to a chosen receptor without extensive prior
      knowledge of the site structure, and several biological systems have been
      targeted. In the vast field of glycoscience, the concept may find special
      perspective in response to the highly complex nature of carbohydrate-protein
      interactions. This chapter summarises studies that have been performed using DCC
      in biological systems, with special emphasis on glycoscience.

PMID- 12223269
TI  - Animal lectins: a historical introduction and overview.
AB  - Some proteins we now regard as animal lectins were discovered before plant
      lectins, though many were not recognised as carbohydrate-binding proteins for
      many years after first being reported. As recently as 1988, most animal lectins
      were thought to belong to one of two primary structural families, the C-type and
      S-type (presently known as galectins) lectins. However, it is now clear that
      animal lectin activity is found in association with an astonishing diversity of
      primary structures. At least 12 structural families are known to exist, while
      many other lectins have structures apparently unique amongst carbohydrate-binding
      proteins, although some of those "orphans" belong to recognised protein families
      that are otherwise not associated with sugar recognition. Furthermore, many
      animal lectins also bind structures other than carbohydrates via protein-protein,
      protein-lipid or protein-nucleic acid interactions. While animal lectins
      undoubtedly fulfil a variety of functions, many could be considered in general
      terms to be recognition molecules within the immune system. More specifically,
      lectins have been implicated in direct first-line defence against pathogens, cell
      trafficking, immune regulation and prevention of autoimmunity.

PMID- 12223270
TI  - Principles of structures of animal and plant lectins.
AB  - Lectins form a diverse group of protein families that have in common their
      ability to specifically recognize certain carbohydrates. Crystal structures of
      members of the different animal and plant lectin families have revealed a wide
      variety of lectin folds and carbohydrate binding site architectures. Despite this
      large variability, a number of interesting cases of convergent as well as
      divergent evolution among animal and plant lectin families can be noted. These
      similarities exist at the levels of the protein fold, the architecture of the
      binding site as well as quaternary structure and may be derived from similar
      functional needs.

PMID- 12223271
TI  - Galectinomics: finding themes in complexity.
AB  - With the rapid explosion of genomic sequence databases, there has been an
      equivalent boom in genomics, the use of sequence information to define and
      compare gene families and their organization across diverse species. Such
      expansion of the galectin family by "galectinomics" to include many new members
      is reviewed here. The galectin gene family is evolutionarily ancient with
      representatives in vertebrates, invertebrates, and even in protists. Although the
      identification of many novel galectin relatives in widely divergent organisms
      (including Arabidopsis, Drosophila, Caenorhabditis, Danio, Xenopus, and human)
      has added significantly to the size and complexity of this intriguing protein
      family, several common themes arise, which suggest promising new research
      targets.

PMID- 12223272
TI  - Oligosaccharide specificity of galectins: a search by frontal affinity
      chromatography.
AB  - Galectins are widely distributed sugar-binding proteins whose basic specificity
      for beta-galactosides is conserved by evolutionarily preserved carbohydrate
      recognition domains (CRDs). Although they have long been believed to be involved
      in diverse biological phenomena critical for multicellular organisms, in only few
      a cases has it been proved that their in vivo functions are actually based on
      specific recognition of the complex carbohydrates expressed on cell surfaces. To
      obtain clues to understand the physiological roles of diverse members of the
      galectin family, detailed analysis of their sugar-binding specificity is
      necessary from a comparative viewpoint. For this purpose, we recently reinforced
      a conventional system for frontal affinity chromatography (FAC) [J. Chromatogr.,
      B, Biomed. Sci. Appl. 771 (2002) 67-87]. By using this system, we quantitatively
      analyzed the interactions at 20 degrees C between 13 galectins including 16 CRDs
      originating from mammals, chick, nematode, sponge, and mushroom, with 41
      pyridylaminated (PA) oligosaccharides. As a result, it was confirmed that
      galectins require three OH groups of N-acetyllactosamine, as had previously been
      denoted, i.e., 4-OH and 6-OH of Gal, and 3-OH of GlcNAc. As a matter of fact, no
      galectin could bind to glycolipid-type glycans (e.g., GM2, GA2, Gb3), complex
      type N-glycans, of which both 6-OH groups are sialylated, nor Le-related antigens
      (e.g., Le(x), Le(a)). On the other hand, considerable diversity was observed for
      individual galectins in binding specificity in terms of (1) branching of N
      glycans, (2) repeating of N-acetyllactosamine units, or (3) substitutions at 2-OH
      or 3-OH groups of nonreducing terminal Gal. Although most galectins showed
      moderately enhanced affinity for branched N-glycans or repeated N
      acetyllactosamines, some of them had extremely enhanced affinity for either of
      these multivalent glycans. Some galectins also showed particular preference for
      alpha1-2Fuc-, alpha1-3Gal-, alpha1-3GalNAc-, or alpha2-3NeuAc-modified glycans.
      To summarize, galectins have evolved their sugar-binding specificity by enhancing
      affinity to either "branched", "repeated", or "substituted" glycans, while
      conserving their ability to recognize basic disaccharide units, Galbeta1
      3/4GlcNAc. On these bases, they are considered to exert specialized functions in
      diverse biological phenomena, which may include formation of local cell-surface
      microdomains (raft) by sorting glycoconjugate members for each cell type.

PMID- 12223273
TI  - Binding and cross-linking properties of galectins.
AB  - The galectins are a family of animal lectins that possess similar carbohydrate
      binding specificities and conserved consensus sequences. The biological
      properties of mammalian galectins include the regulation of inflammation, cell
      adhesion, cell proliferation and cell death. Evidence suggests that the
      biological activities of the galectins are related to their multivalent binding
      properties since most galectins possess two carbohydrate recognition domains and
      are therefore bivalent. For example, galectin-1, which is dimeric, binds and
      cross-links specific glycoprotein counter-receptors on the surface of human T
      cells leading to apoptosis [J. Immunol. 163 (1999) 3801]. Different galectin-1
      counter-receptors associated with specific phosphatase or kinase activities
      formed separate clusters on the surface of the cells as a result of the lectin
      binding to the carbohydrate chains of the respective glycoproteins. Importantly,
      monovalent galectin-1 is inactive in this system. This indicates that the
      separation and organization of signaling molecules that result from galectin-1
      binding is involved in the apoptotic signal. The separation of specific
      glycoprotein receptors induced by galectin-1 binding was modeled on the basis of
      molecular and structural studies of the binding of lectins to multivalent
      carbohydrates resulting in the formation of specific two- and three-dimensional
      cross-linked lattices [Biochemistry 36 (1997) 15073]. In this article, the
      binding and cross-linking properties of galectin-1 and other lectins are reviewed
      as a model for the biological signal transduction properties of the galectin
      family of animal lectins.

PMID- 12223274
TI  - Intracellular functions of galectins.
AB  - Many galectin family members are detected primarily intracellularly in most of
      the systems studied, although certain members can be found both inside and
      outside of cells. Specific functions that are consistent with their intracellular
      localization have now been documented for some of the galectins. Galectin-1 and 
      3 have been identified as redundant pre-mRNA splicing factors. Galectin-3, -7,
      and -12 have been shown to regulate cell growth and apoptosis, being either anti
      apoptotic or pro-apoptotic. Galectin-3 and -12 have been shown to regulate the
      cell cycle. In some cases, the mechanisms by which galectins exert their
      functions have been partially delineated in relation to known intracellular
      pathways associated with these processes. In addition, a number of intracellular
      proteins involved in these processes have been identified as the interacting
      ligands of certain galectins. This review summarizes the intracellular activities
      displayed by several galectins and discusses the possible underlying mechanisms.

PMID- 12223275
TI  - Role of galectins in inflammatory and immunomodulatory processes.
AB  - Galectins are members of a highly conserved family of beta-galactoside-binding
      animal lectins. Presently, more than 14 members have been identified and
      additional homologues are likely to be discovered. Given their conservation
      throughout animal evolution, it is not surprising that they could play key roles
      in innate and adaptive immune responses, through sugar-dependent and -independent
      mechanisms. Recently, it has become increasingly clear that galectins can
      differentially affect cellular activation and function. These biological effects
      attracted attention of researchers in cell biology, biochemistry, glycobiology
      and immunology, not only in the mode of action of galectins, but also in their
      role as putative modulators of immune surveillance, apoptosis, cell adhesion and
      chemotaxis. Here we will summarize the state-of-the-art of the effects of
      galectins in inflammatory and immunomodulatory processes. In addition, we will
      discuss in-depth the current knowledge about the effects of this enigmatic family
      of animal lectins and their glycoligands in the progression, diagnosis and
      treatment of different pathological processes such as autoimmunity, allergy,
      infection and chronic inflammation.

PMID- 12223276
TI  - Galectins and cancer.
AB  - The galectins are a family of proteins that are distributed widely in all living
      organisms. All of them share galactose-specificity. At present, 14 members of the
      family are characterized in mammals. The galectins have been implicated in many
      essential functions including development, differentiation, cell-cell adhesion,
      cell-matrix interaction, growth regulation, apoptosis, RNA splicing, and tumor
      metastasis. Although efforts have mostly focused on the possible function of
      galectins in tumor development and invasiveness, their precise role in this field
      is still debated. This review discusses the recent way in which the expression of
      galectins and galectin-binding sites may affect the behavior of a variety of
      human neoplastic tissues.

PMID- 12223277
TI  - I-type lectins.
AB  - The immunoglobulin superfamily is a large category of proteins defined by their
      structural similarity to immunoglobulins. The majority of these proteins are
      involved in protein-protein binding as receptors, antibodies or cell adhesion
      molecules. The I-type lectins are a subset of the immunoglobulin superfamily that
      are capable of carbohydrate-protein interactions. There are I-type lectins
      recognizing sialic acids, other sugars and glycosaminoglycans. The occurrence,
      structure, binding properties and (potential) biological functions of the I-type
      lectins are reviewed here.

PMID- 12223278
TI  - P-type lectins.
AB  - The two members of the P-type lectin family, the cation-dependent mannose 6
      phosphate receptor (CD-MPR) and the insulin-like growth factor II/mannose 6
      phosphate receptor (IGF-II/MPR), are distinguished from all other lectins by
      their ability to recognize phosphorylated mannose residues. The P-type lectins
      play an essential role in the generation of functional lysosomes within the cells
      of higher eukaryotes by directing newly synthesized lysosomal enzymes bearing the
      mannose 6-phosphate (M6P) signal to lysosomes. At the cell surface, the IGF
      II/MPR also binds to the nonglycosylated polypeptide hormone, IGF-II, targeting
      this potent mitogenic factor for degradation in lysosomes. Moreover, in recent
      years, the multifunctional nature of the IGF-II/MPR has become increasingly
      apparent, as the list of extracellular ligands recognized by this receptor has
      grown to include a diverse spectrum of M6P-containing proteins as well as
      nonglycosylated ligands, implicating a role for the IGF-II/MPR in a number of
      important physiological pathways. Recent investigations have provided valuable
      insights into the molecular basis of ligand recognition by the MPRs as well as
      the complex intracellular trafficking pathways traversed by these receptors. This
      review provides a current view on the structures, functions, and medical
      relevance of the P-type lectins.

PMID- 12223279
TI  - Glycans as endocytosis signals: the cases of the asialoglycoprotein and
      hyaluronan/chondroitin sulfate receptors.
AB  - Animal cells internalize specific extracellular macromolecules (ligands) by using
      specialized cell surface receptors that operate through a complex and highly
      regulated process known as receptor-mediated endocytosis, which involves the
      binding, internalization, and transfer of ligands through a series of distinct
      intracellular compartments. For the uptake of a variety of carbohydrate
      containing macromolecules, such as glycoproteins, animal cells use specialized
      membrane-bound lectins as endocytic receptors that recognize different sugar
      residues or carbohydrate structures present on various ligands. The hepatic
      asialoglycoprotein receptor, which recognizes glycoconjugates containing terminal
      galactose or N-acetylgalactosamine residues, was the first membrane lectin
      discovered and has been a classical system for studying receptor-mediated
      endocytosis. Studies of how the asialoglycoprotein receptor functions have led to
      the discovery of two functionally distinct, parallel pathways of clathrin
      mediated endocytosis (called the State 1 and State 2 pathways), which may also be
      utilized by all the other endocytic recycling receptor systems. Another endocytic
      membrane lectin, the hyaluronan/chondroitin sulfate receptor, which has recently
      been purified and cloned, is responsible for the turnover in mammals of these
      glycosaminoglycans, which are important components of extracellular matrices. We
      discuss the characteristics and physiological importance of these two proteins as
      examples of how lectins can function as endocytic receptors.

PMID- 12223280
TI  - The mannose receptor family.
AB  - The mannose receptor family comprises four glycoproteins each of which is a type
      I transmembrane receptor with an N-terminal cysteine-rich domain, a single
      fibronectin type II (FNII) domain and eight to ten C-type lectin-like domains
      (CTLDs). Characteristically, these proteins are able to recycle between the
      plasma membrane and the endosomal apparatus due to discrete motifs present within
      their cytoplasmic domains. This review discusses the structure and function of
      these four proteins-the mannose receptor (MR), the M-type receptor for secretory
      phospholipases A(2) (PLA(2)R), DEC-205/gp200-MR6 and Endo180/uPARAP. Despite
      their overall structural similarity, these four receptors have evolved to use
      different domains to interact with discrete ligands. In addition, they differ in
      their ability to mediate endocytic and phagocytic events and in their
      intracellular destinations. Together, they represent a unique group of
      multidomain, multifunctional receptors.

PMID- 12223281
TI  - Collectins and ficolins: sugar pattern recognition molecules of the mammalian
      innate immune system.
AB  - Collectins and ficolins represent two important groups of pattern recognition
      molecules, which bind to oligosaccharide structures on the surface of
      microorganisms, leading to the killing of bound microbes through complement
      activation and phagocytosis. Collectins and ficolins bear no significant sequence
      homology except for the presence of collagen-like sequences over the N-terminal
      halves of the polypeptides that enable the assembly of these molecules into
      oligomeric structures. Collectins and ficolins both contain lectin activities
      within the C-terminal halves of their polypeptides, the C-type carbohydrate
      recognition domain (CRDs) and fibrinogen beta/gamma (homology) (FBG) domain,
      respectively. These domains form trimeric clusters at the ends of the collagen
      triple helices emanating from a central hub, where the N-terminal ends of the
      polypeptides merge. The collectins and ficolins seem to have evolved to recognize
      the surface sugar codes of microbes and their binding, to these arrays of cell
      surface carbohydrate molecules, targets the microbe for subsequent clearance by
      phagocytic cells.

PMID- 12223282
TI  - Mannan-binding lectin: clinical significance and applications.
AB  - Mannan-binding lectin (MBL) is a collectin (protein with both collagen-like and C
      type lectin domains) synthesised in the liver and secreted into the bloodstream.
      Its plasma concentration is for the most part genetically determined by a series
      of allelic dimorphisms located both in the structural gene and in the promoter
      region. Genotypes made up of combinations of seven haplotypes are mainly
      responsible for a 1000-fold concentration variation found in human beings. MBL is
      a pattern recognition molecule able to bind repeating sugar arrays on many
      microbial surfaces, and can activate complement via associated serine proteases.
      A poorly defined proportion (roughly 10%) of the population with the lowest MBL
      concentrations is thought to be MBL insufficient and more vulnerable to a variety
      of infectious and noninfectious disorders. The evidence that MBL makes an
      important contribution to innate immunity, by increasing susceptibility to
      disease and/or affecting the course of disease, is discussed in detail.
      Preliminary results from MBL replacement therapy are encouraging, and extension
      of this approach to large-scale randomised clinical trials would provide solid
      evidence concerning the physiological significance of this protein.

PMID- 12223283
TI  - Molecular basis of non-self recognition by the horseshoe crab tachylectins.
AB  - The self/non-self discrimination by innate immunity through simple ligands
      universally expressed both on pathogens and hosts, such as monosaccharides and
      acetyl group, depends on the density or clustering patterns of the ligands. The
      specific recognition by the horseshoe crab tachylectins with a propeller-like
      fold or a propeller-like oligomeric arrangement is reinforced by the short
      distance between the individual binding sites that interact with pathogen
      associated molecular patterns (PAMPs). There is virtually no conformational
      change in the main or side chains of tachylectins upon binding with the ligands.
      This low structural flexibility of the propeller structures must be very
      important for specific interaction with PAMPs. Mammalian lectins, such as mannose
      binding lectin and ficolins, trigger complement activation through the lectin
      pathway in the form of opsonins. However, tachylectins have no effector
      collagenous domains and no lectin-associated serine proteases found in the
      mammalian lectins. Furthermore, no complement-like proteins have been found in
      horseshoe crabs, except for alpha(2)-macroglobulin. The mystery of the molecular
      mechanism of the scavenging pathway of pathogens in horseshoe crabs remains to be
      solved.

PMID- 12223284
TI  - Lectin activities of cytokines: functions and putative carbohydrate-recognition
      domains.
AB  - The discovery that some cytokines have carbohydrate-binding (lectin) properties
      opens new concepts in the understanding of their mechanism of action. The
      carbohydrate-recognition domain (CRD), which is localized at the opposite of the
      receptor-binding domain, makes these molecules bi-functional. The expression of
      the biological activity of the cytokine relies on its carbohydrate-binding
      activity, which allows the association of the cytokine receptor with molecular
      complexes comprising the specific kinase/phosphatase involved in receptor
      phosphorylation/dephosphorylation and in specific signal transduction. As a
      correlate, a cytokine can act only on cells possessing both the receptor and the
      ligand. Two cytokines using the same receptor can have different target cells and
      functions because of their different lectin activities. Based on a few examples,
      the CRD can be predicted based on the 3-D structures of the molecules.

PMID- 12223285
TI  - Report of the "Bioterrorism Workshop." Duke University Thomas Center on April 2
      4, 2002, organized by US Army Research Office.

PMID- 12223286
TI  - Identification of medically relevant microorganisms by vibrational spectroscopy.
AB  - In the recent years, vibrational spectroscopies (infrared and Raman spectroscopy)
      have been developed for all sorts of analyses in microbiology. Important features
      of these methods are the relative ease with which measurements can be performed.
      Furthermore, in order to obtain infrared or Raman spectra, there is only a
      limited amount of sample handling involved without the need for expensive
      chemicals, labels or dyes. Here, we review the potential application of
      vibrational spectroscopies for the use in medical microbiology. After describing
      some of the basics of the techniques, considerations on reproducibility and
      standardisation are presented. Finally, the use of infrared and Raman
      spectroscopy for the (rapid) identification of medically relevant microorganisms
      is discussed. It can be concluded that vibrational spectroscopies show high
      potential as novel methods in medical microbiology.

PMID- 12223287
TI  - Evaluation of methods to solubilize and analyze cell-associated ectoenzymes.
AB  - To quantify the functional diversity of microbes that use hydrolytic ectoenzymes,
      the feasibility of separating cell-associated proteins on polyacrylamide gels and
      detecting enzyme activity via fluorescent substrate analogs for aminopeptidases,
      glucosidases, and esterases was determined. More than 87% of aminopeptidase
      activity was associated with particulate cell material in all of the 10 Gram
      negative bacterial strains that were investigated. Although 7-amino-4
      methylcoumarin-leucine (AMC-leucine) provided high activities after incubation
      with eight strains from the Cytophaga-Flexibacter-Bacteroides group, very poor
      responses were noted with two gamma Proteobacteria that grew well on protein.
      Therefore, this molecule was not a universal substrate for aminopeptidases.
      Methods of increasing stringency were evaluated to release enzyme activity from
      particulate material. Some methods (treatment with 0.1% Triton X-100) gave good
      results with some but not all strains. Cell lysis by shearing produced the most
      consistent results. Ectoenzyme activities could be localized on polyacrylamide
      gels using fluorescent substrate analogs. However, some activities were located
      in high molecular weight complexes, and methods that disrupted these complexes
      (such as treatment with sodium dodecyl sulfate at elevated temperature) destroyed
      enzyme activity. In addition, the enzymes from different strains showed the same
      electrophoretic mobility. Therefore, the analysis of functional diversity by this
      approach is limited by the difficulty in solubilizing particulate enzymes under
      conditions where they retain activity.

PMID- 12223288
TI  - A real time PCR assay for the detection and quantitation of Mycobacterium avium
      subsp. paratuberculosis using SYBR Green and the Light Cycler.
AB  - Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of
      Johne's disease, and may also contribute to the onset and development of Crohn's
      disease in humans. Due to its reported heat resistance, isolation from
      pasteurised milk and the potential for transmission of MAP through environmental
      sources, rapid detection is imperative. Here, we present a rapid real time PCR
      assay for MAP that can simultaneously detect and quantify this organism in the
      laboratory using SYBR Green and the Lightcycler (LC). This method uses the highly
      characterised and specific P90, P91 primers, which amplify a 400-bp region of the
      IS900 element. Using quantified standard DNA, this assay can accurately detect as
      few as 20 copies (equivalent to approximately 1.5 organisms). The method is
      effective using a variety of templates including isolated MAP DNA, pure colonies
      or liquid culture sources, and can also work in the presence of contaminating
      bacteria. A useful application of this assay is the ability to accurately and
      rapidly quantitate the number of MAP cells in liquid culture as determined by
      comparison to previously enumerated standards.

PMID- 12223289
TI  - Rapid differentiation of Old World Leishmania species by LightCycler polymerase
      chain reaction and melting curve analysis.
AB  - A LightCycler real-time polymerase chain reaction (PCR) assay has been developed
      to detect and differentiate four of the main Leishmania species of the Old World.
      The assay is based on fluorescence melting curve analysis of PCR products
      generated from the minicircles of kinetoplast DNA. According to the melting
      temperature, which is a function of GC/AT ratio, length and nucleotide sequences
      of the amplified product, Leishmania major was differentiated from L. donovani
      and from L. tropica and L. infantum. Melting curves analysis offers a rapid
      alternative for identification of species in diagnostic or epidemiological
      studies of leishmaniasis or asymptomatic parasitism.

PMID- 12223290
TI  - Checkerboard DNA-DNA hybridisation technology focused on the analysis of Gram
      positive cariogenic bacteria.
AB  - Checkerboard DNA-DNA hybridisation enabled the quantitative analysis of plaque
      samples against 40 microbial species simultaneously, using digoxygenin-labelled,
      whole-genome DNA probes. This technique was initially developed to study the
      predominantly Gram-negative sub-gingival plaque microbiota. The aim of this study
      was to apply it to a suite of predominantly Gram-positive microorganisms, such as
      those implicated in cariogenesis. To specifically target Gram-positive species
      (and Candida albicans) required optimisation and modification of DNA extraction,
      prehybridisation, hybridisation, and antibody detection conditions. The
      suitability of the revised technique for clinical and epidemiological studies was
      confirmed using interproximal plaque from small groups of 5- to 6-year-old
      children of high (decayed, missing, or filled teeth (dmft)> or =5, n=8) and zero
      (n=5) caries rates.

PMID- 12223291
TI  - Comparison of two selective media for the detection and enumeration of
      Lactobacilli in human faeces.
AB  - The enumeration of faecal bacteria is an important requirement for many studies
      of bowel health. One approach is the use of selective culture media for the
      culture and identification of genera or species from faeces. This study compares
      the culture of Lactobacilli from dilution series of faecal samples from six
      healthy human volunteers on two commonly used media, LAMVAB and Rogosa agar.
      Colonies were counted after a 72-h anaerobic incubation at 37 degrees C, and
      colony morphology recorded by a single observer. DNA was isolated from a
      representative number of colonies and genus-specific PCR, single-stranded
      conformation polymorphism (SSCP) and DNA sequencing performed. Total colony
      counts ranged from <3.00 to 7.48 log(10) cfu/g of faeces for LAMVAB and 5.09 to
      7.66 log(10) cfu/g for Rogosa. For each subject, the total colony count was
      higher on Rogosa than that obtained with LAMVAB agar. SSCP analysis and DNA
      sequencing indicated that colony morphology was not an accurate predictor of
      genus identity. Growth of two species, Lactobacillus acidophilus and
      Lactobacillus gasseri, was not supported on LAMVAB medium. Rogosa agar was more
      likely to support growth of non-Lactobacillus species. Therefore, neither medium
      gave a fully accurate representation of the Lactobacilli species present in human
      faecal samples.

PMID- 12223292
TI  - Inclusion counter: a public domain image analysis system for measurement of
      Chlamydiaceae growth in vitro.
AB  - The traditional method of measuring chlamydial growth in vitro, counting
      Chlamydiaceae inclusions by eye, is time-consuming and error prone. This paper
      describes a novel automated image analysis system suitable for high-throughput
      screening of novel anti-Chlamydiaceae compounds. The software, Inclusion Counter
      v3.0, is freely available in the public domain (http://www.image-analysis.co.uk).

PMID- 12223293
TI  - Toxoplasma gondii in vitro culture for experimentation.
AB  - The aim of this study was to develop a culture method for Toxoplasma gondii that
      could provide fresh viable tachyzoites as and when required. When T. gondii was
      continuously maintained in HeLa cell cultures at 37 degrees C, the time to
      harvest varied from 48 to 144 h. Tachyzoite yields of > or = 1 x 10(6)/ml and >
      or = 90% viable were obtained from 519/882 (58.8%) cultures and 120/155 (77.4%)
      harvests were successfully used in the dye test. When cultures were transferred
      from 37 to 25 degrees C when maximally infected (48-54-h post-infection), they
      could be stabilised and tachyzoites could be harvested as required, up to 168 h
      later. When harvested from 25 degrees C, significantly more cultures 783/811
      (96.5%) produced tachyzoite yields > or = 1 x 10(6)/ml > or = 90% viable (p <
      0.001). Tachyzoite quality also significantly improved and 206/224 harvests
      (91.9%) (p < 0.001) were successfully used in the dye test. We have demonstrated
      that tachyzoites can be maintained at dye test quality for at least 7 days in
      HeLa cultures at 25 degrees C. The system is flexible and robust and provides a
      means whereby tachyzoites of standard quality can be stored for use in
      experimental models as and when required.

PMID- 12223294
TI  - Multiple enzyme restriction fragment length polymorphism analysis for high
      resolution distinction of Pseudomonas (sensu stricto) 16S rRNA genes.
AB  - Members of the genus Pseudomonas (sensu stricto) are important phytopathogens and
      agents of human infections, while other strains and species have beneficial
      bioremediation and biocontrol activities. Traditionally, these important species
      have been difficult to differentiate phenotypically; thus, rRNA lineage analyses
      have often been invoked. In this report, a newly developed approach is described
      to rapidly detect and distinguish fluorescent Pseudomonas isolates: PCR
      amplification of a Pseudomonas-specific 990-bp ribosomal RNA gene (rDNA) fragment
      [Appl. Environ. Microbiol. 64 (1998) 2545.] coupled with multiple enzyme
      restriction fragment length polymorphism (MERFLP) analysis using a single
      digestion mixture of AluI, HinfI, RsaI, and Tru9I incubated at 37 degrees C. The
      method distinguished 116 published sequences and 47 reference strains of
      authentic Pseudomonas representing 28 nomenspecies. A total of 55% (64/116) of
      the sequences analyzed by MERFLP were grouped into distinct phylogenetic clusters
      including Pseudomonas putida, P. syringae, P. aeruginosa, P. stutzeri, and P.
      fluorescens. The utility of the MERFLPs was confirmed when 100% (33/33) of the
      above named control reference strains were correctly placed into their
      phylogenetic clusters. The environmental relevance of the MERFLP method was
      confirmed when 67% of 28 forest and agricultural soil-derived presumptive
      Pseudomonas environmental clones and isolates were placed into the five major
      pseudomonad clusters, one clone fell into the P. agarici cluster, and five clones
      clustered near related pseudomonads. These data demonstrated that the PCR-MERFLP
      protocol provides an efficient and powerful tool for distinguishing isolates and
      rDNA gene libraries of environmental Pseudomonas species.

PMID- 12223295
TI  - Evaluation of procedures for reliable PCR detection of Ralstonia solanacearum in
      common natural substrates.
AB  - Several procedures were compared for reliable PCR detection of Ralstonia
      solanacearum in common substrates (plant, seed, water and soil). In order to
      prevent the inhibition of PCR by substances contained in crude extracts, numerous
      DNA extraction procedures as well as additives to buffers or PCR mixtures were
      checked. Our results showed that the efficiency of these methods or compounds
      depended greatly upon the nature of the sample. Consequently, preparation of
      samples prior to PCR depended upon sample origin. Simple methods such as a
      combined PVPP/BSA treatment or the association of filtration and centrifugation
      for detecting the bacterium in plant or water samples were very powerful. DNA
      capture also efficiently overcame PCR inhibition problems and ensured the
      detection of R. solanacearum in environmental samples. However, the commercial
      DNA extraction QIAamp kit appeared to be the most effective tool to guarantee the
      accurate PCR detection of the pathogen whatever the origin of the sample; this
      was particularly true for soil samples where the commonly used methods for the
      detection of R. solanacearum were inefficient. This study demonstrates that using
      an appropriate procedure, PCR is a useful and powerful tool for detecting low
      levels of R. solanacearum populations in their natural habitats.

PMID- 12223296
TI  - Factors affecting the performance of 5' nuclease PCR assays for Listeria
      monocytogenes detection.
AB  - The design and operating parameters affecting the performance of 5' nuclease PCR
      (TaqMan) assays for the detection of Listeria monocytogenes was investigated. A
      system previously developed and based on the hlyA gene was used as a model [Appl.
      Environ. Microbiol. 61 (1995) 3724]. A series of fluorogenic probes labeled with
      a reporter and a quencher dye was synthesized to explore the effect of probe
      position and sequence content on the efficiency of probe hydrolysis. In addition,
      a series of PCR primer pairs that altered the distance between the upstream
      primer and the interceding probe was examined. The effects of various assay
      parameters were evaluated by measuring the ratio of the fluorescence intensity of
      the reporter dye over the quencher dye (deltaRQ). For a given probe sequence, the
      deltaRQ was typically lower if the 5' terminus was a G residue. Decreasing the
      probe concentration increased the deltaRQ, although this was at the expense of
      reproducibility in the assay readout. The distance between the upstream primer
      and the interceding probe has a significant effect on probe hydrolysis. Reducing
      the primer-probe distance from, for example, 127 to 4 nt increased the deltaRQ
      from 2.87 to 5.00. These general rules were used to develop a 5' nuclease PCR
      (TaqMan) assay with enhanced signal output, providing higher and more
      reproducible deltaRQ values for L. monocytogenes detection.

PMID- 12223297
TI  - Detection of Escherichia coli O157:H7 using immunomagnetic separation and
      absorbance measurement.
AB  - An assay system for detection of Escherichia coli O157:H7 was developed based on
      immunomagnetic separation of the target pathogen from samples and absorbance
      measurement of p-nitrophenol at 400 nm from p-nitrophenyl phosphate hydrolysis by
      alkaline phosphatase (EC 3.1.3.1) on the "sandwich" structure complexes
      (antibodies coated onto micromagnetic beads--E. coli O157:H7-antibodies
      conjugated with the enzyme) formed on the microbead surface. The effects of
      immunoreaction time, phosphate buffer concentration, pH and temperature on the
      immunomagnetic separation of E. coli O157:H7 from samples were determined and the
      conditions used for the separation were 1-h reaction time, 1.0 x 10(-2) M PBS, pH
      8.0 and 33 degrees C in this system. The effects of MgCl(2) concentration, Tris
      buffer concentration, pH and temperature on the activity of alkaline phosphatase
      conjugated on the immuno-"sandwich" structure complexes were investigated after
      immunomagnetic separation of the target pathogen and the conditions used for the
      enzymatic amplification were 1.0 x 10(-4) M MgCl(2), 1.0 M Tris buffer, pH 8.0,
      28 degrees C and 30-min reaction time during the assay. The selectivity of the
      system was examined and no interference from the other pathogens including
      Salmonella typhimurium, Campylobacter jejuni and Listeria monocytogenes was
      observed. Its working range was from 3.2 x 10(2) to 3.2 x 10(4) CFU/ml, and the
      relative standard deviation was 2.5-9.9%. The total detection time was less than
      2 h.

PMID- 12223298
TI  - Two-vector assay as a tool for examining Spo0A gene transcription regulation.
AB  - We have modified an assay using two compatible vectors that coexist in
      Escherichia coli cells and applied it in the investigation of the transcriptional
      activity of Spo0A, a key regulator of sporulation in Bacillus subtilis. We have
      chosen the promoters of the Spo0A dependent genes, spoIIE and spoIIA, involved in
      sporulation, in order to study the transcription activity solely of the DNA
      binding domain of Spo0A. We have prepared the two-vector system so that one
      vector contained the cloned C-Spo0A under the control of an inducible promoter,
      and the second vector (the promoter probe vector), was composed of the Spo0A
      dependent spoIIE and spoIIA promoters. Using this two-vector system in E. coli,
      we proved that C-Spo0A is able to interact with the E. coli transcription
      apparatus, recognizes both promoters and activates transcription from these
      promoters.

PMID- 12223299
TI  - An internal control for the diagnosis of crown gall by PCR.
AB  - The addition of an internal control (IC) at the appropriate concentration enables
      recognize of false negatives in the detection of Agrobacterium tumefaciens and
      improves the reliability of PCR for crown gall diagnosis. Co-amplification of the
      IC and target sequence from A. tumefaciens ensures the attainment of at least one
      amplification product in every PCR reaction if the DNA extracted is of high
      enough quality to be amplified.

PMID- 12223300
TI  - Biolistic transformation of Trichoderma reesei using the Bio-Rad seven barrels
      Hepta Adaptor system.
AB  - Effective biolistic transformation of intact conidia from the filamentous fungus
      Trichoderma reesei was achieved using the Bio-Rad Hepta Adaptor system with seven
      barrels for particle launch. Transformation frequencies of up to 39 colonies per
      microg of circular DNA and 37 colonies per microg of linear DNA were obtained at
      an optimal target distance of 3 cm and a helium pressure of 1350 psi. These
      values are about 3.5- to 6-fold higher than transformant yields reported earlier
      for T. reesei using the hygromycin phosphotransferase (hph) gene conferring
      resistance to the antibiotic hygromycin B as a selectable marker in combination
      with the PDS-1000/He single barrel system. High mitotic stability of the
      transformants (98-100%) was demonstrated. The Hepta Adaptor device allowing
      bombardment of seven lots of conidia in a single plate offers clear advantage in
      terms of transformant numbers over the single barrel system where target cells
      are restricted to the center of the plate.

PMID- 12223301
TI  - A simple method for the measurement of bacterial particle conductivities.
AB  - A method was developed for the measurement of the bacterial particle
      conductivity, based on the measurement of the conductivity of a bacterial cell
      suspension sigma(s) and the suspending medium sigma(m). A line plotted through
      sigma(s) - sigma(m) versus sigma(m) crosses the x-axis at sigma(m) = sigma(p),
      independent of the bacterial cell concentration. The method does not require
      anything more complex than a centrifuge and a conductivity meter. Knowledge of
      the bacterial particle conductivity is of importance in, for example, the
      dielectrophoretic separation, manipulation and trapping of bacterial cells, as
      well as the study of their physiological state.

PMID- 12223302
TI  - Further modification of the Hodge test to screen AmpC beta-lactamase (CMY-1)
      producing strains of Escherichia coli and Klebsiella pneumoniae.
AB  - Cefoxitin-resistant Escherichia coli and Klebsiella pneumoniae are widespread in
      Korea. Significant proportions of them are considered to be CMY-1 producers. For
      effective screening of CMY-1 producers, the Hodge test was modified by using a
      cefoxitin disk and the performance was evaluated. The sensitivity and specifity
      of the test were 100% and 94.9%, respectively. The test was easier to perform
      than the three-dimensional extract test. This modified test should be suitable
      for screening CMY-1-producing strains of E. coli and K. pneumoniae.

PMID- 12223303
TI  - Media for cultivation of indoor streptomycetes.
AB  - The growth of 10 indoor Streptomyces spp. isolates on nutritionally complex and
      selective 26 media revealed that the mycelium production had a tendency to
      increase in order: starch-casein < glycerol-arginine < glucose-tryptone, and
      NH(4)NO(3) < Na-caseinate-asparagine. Yeast extract increased mycelium
      biosynthesis, but not always the growth rate. The strains belonging to
      streptomycetes most common environmental isolates produced visible mycelium in 5
      days on all media.

PMID- 12223304
TI  - Zymographic detection of cinnamic acid decarboxylase activity.
AB  - The manuscript includes a concise description of a new, fast and simple method
      for detection of cinnamic acid decarboxylase activity. The method is based on a
      color shift caused a by pH change and may be an excellent procedure for large
      screenings of samples from natural sources, as it involves no complex sample
      processing or purification. The method developed can be used in preliminary
      approaches to biotransformation processes involving detection of hydroxycinnamic
      acid decarboxylase activity.

PMID- 12223305
TI  - Development of a microslide agglutination assay with the aid of an inexpensive
      projection microscope.
AB  - A microslide agglutination assay was developed involving the mixing of 2.5 microl
      each of antiserum and a cell suspension of Listeria monocytogenes. Cell
      agglutination in the final volume of 5.0 microl was visually observed at a direct
      magnification of 22 x on the projection screen of an inexpensive 20 US dollar
      projection microscope. The procedure has the advantage of increasing by a factor
      of 20 the number of agglutination assays that can be performed with a given
      volume of antiserum with the use of an inexpensive optical projection system.

PMID- 12223307
TI  - Infectivity of amyloid diseases.
AB  - To date, transmissibility of amyloid diseases has not been thoroughly
      investigated. Although only some of these conformational disorders are considered
      infectious, all amyloid diseases could be infectious under certain conditions.
      For transmissibility, endogenous expression of an amyloidogenic peptide required,
      as well as the presence of an inoculum that is rich in amyloid fibrils and/or
      their precursors. Notably, administration of one type of amyloid might result in
      deposition of a different amyloid. Various cofactors could be essential for
      transmission - some might chaperone the amyloid peptides and/or fibrils, thereby
      directly facilitating their propagation; others might indirectly stabilize and/or
      increase levels of conformers with a high beta-sheet content. It is possible that
      these chaperones are induced by inflammation, which itself can lead to secondary
      amyloidosis. Thus, amyloid-related therapeutic approaches should not be based on
      administration of amyloidogenic peptides in conjunction with an inflammatory
      stimulus, such as in a recently halted clinical trial for Alzheimer's disease.

PMID- 12223312
TI  - Papillomaviruses: death-defying acts in skin cancer.
AB  - Ultraviolet (UV) radiation is an environmental agent that has a major impact on
      humans, and cumulative exposure poses a serious risk in terms of developing skin
      cancer. Acute doses of UV induce apoptotic cell death in the skin via signalling
      pathways that are, in part, dependent on the p53 tumour suppressor protein.
      However, p53-independent mechanisms have also been described. Recent findings
      show that a high proportion of non-melanoma skin cancers contain human
      papillomavirus. The viral E6 protein effectively blocks the epidermal apoptotic
      response to UV and might play a key role in promoting tumour development in
      cooperation with the mutagenic effects of UV.

PMID- 12223313
TI  - The role of PPARs in atherosclerosis.
AB  - Peroxisome proliferator-activated receptors (PPARs) are lipid-activated
      transcription factors that regulate lipid and lipoprotein metabolism, glucose
      homeostasis and inflammation. The PPAR family consists of three proteins, alpha,
      beta/delta and gamma. Recent data suggest that PPAR alpha and gamma activation
      decreases atherosclerosis progression not only by correcting metabolic disorders,
      but also through direct effects on the vascular wall. PPARs modulate the
      recruitment of leukocytes to endothelial cells, control the inflammatory response
      and lipid homeostasis of monocytes/macrophages and regulate inflammatory cytokine
      production by smooth muscle cells. Experiments using animal models of
      atherosclerosis and clinical studies in humans strongly support an anti
      atherosclerotic role for PPAR alpha and gamma in vivo. Thus, PPARs remain
      attractive therapeutic targets for the development of drugs used in the treatment
      of chronic inflammatory diseases such as atherosclerosis. Future research will
      aim for the development of more potent drugs with co-agonist activity on PPAR
      alpha, PPAR beta/delta and/or PPAR gamma as well as tissue and target gene
      selective PPAR receptor modulators (SPPARMs).

PMID- 12223314
TI  - Use of complement inhibitors in tissue injury.
AB  - A great deal of information has accumulated implicating the complement system in
      several human disease processes. Although some of this information is
      circumstantial, protein inhibitors of the complement system have been developed
      and applied successfully to experimental disease models in animals. Two
      inhibitors, soluble complement receptor 1 (sCR1) and anti-C5 monoclonal antibody,
      are now being investigated in a variety of clinical conditions such as systemic
      lupus erythematosus and rheumatoid arthritis (RA), diseases for which current
      therapy has changed little and remains unsatisfactory. Preliminary successes in
      Phase II clinical trials of RA have provided optimism that complement inhibition
      might prove useful in these diseases and become part of standard medical therapy.

PMID- 12223315
TI  - The promiscuous MLL gene links chromosomal translocations to cellular
      differentiation and tumour tropism.
AB  - MLL is a promiscuous gene involved in a diversity of chromosomal fusions in
      haematological malignancies, usually resulting from chromosomal translocations.
      MLL-associated chromosomal rearrangements usually occur in tumours of specific
      haematological lineages, suggesting a crucial role for the MLL fusion partner in
      determining disease phenotype (or tumour tropism). The MLL gene is homologous to
      Drosophila trithorax, and is likewise involved in embryo pattern formation.
      Common themes linking several of the MLL partners include a possible involvement
      in embryo patterning via Hox gene regulation and chromatin remodelling. These
      findings reinforce the link between developmental regulation and chromosomal
      translocations, and indicate the role of chromosomal translocation in activating
      genes capable of determining tumour phenotype in leukaemias and sarcomas.

PMID- 12223316
TI  - Adipogenesis and fat-cell function in obesity and diabetes.
AB  - Normal metabolic balance is maintained by a complex homeostatic system involving
      multiple tissues and organs. Acquired or inherited defects in any part of this
      system can lead to metabolic disorders, such as diabetes and obesity. Adipose
      tissue, once thought to function primarily as a passive depot for the storage of
      excess lipid, is now understood to play a much more active role in metabolic
      regulation, secreting a variety of metabolic hormones and actively functioning to
      prevent deleterious lipid accumulation in other tissues. Here, we review new
      advances in our understanding of adipogenesis and fat-cell function, primarily
      from the perspective of the transcription factor peroxisome proliferator
      activated receptor gamma.

PMID- 12223317
TI  - Mouse models for human deafness: current tools for new fashions.
AB  - Mouse models are one of the major tools used for discovery and characterization
      of genes for non-syndromic deafness in humans. The similarities between the mouse
      and human genomes, and between the physiology and morphology of their auditory
      systems, are striking. This article describes the latest mouse models, including
      spontaneous, 'knockout' and ENU (N-ethyl-N-nitrosourea)-induced mutants, and the
      recent discovery of modifier genes that are involved in mouse deafness; this
      discovery is leading the search for genetic modifiers for human disorders.

PMID- 12223318
TI  - Blood into brain after stroke.
AB  - Using a bone-marrow transplantation chimera-model in mice, we have shown that
      after a cerebral infarction, bone marrow-derived cells differentiate into
      cerebral endothelial cells and NeuN-expressing cells

PMID- 12223321
TI  - [On Index Medicus, our Turkish language and JAMA's big gaffes].

PMID- 12223320
TI  - [Is intermittent dobutamine treatment beneficial in patients with dilated
      cardiomyopathy?].
AB  - OBJECTIVE: Dobutamine is a sympathomimetic drug, which can be used in patients
      with dilated cardiomyopathy (DCM). We investigated the effects of intermittent
      dobutamine use on cardiac parameters and quality of life in patients with DCM.
      METHODS: Twelve patients with ischemic and idiopathic DCM, refractory to
      conventional therapy, have been included in the study. In addition to traditional
      treatment, dobutamine (1-2 micro g/kg/min infusion increasing up to 10 micro
      g/kg/min for 3 days) was administered, and repeated at the 1st, 2nd and 3rd
      months. The patients were evaluated 3 times, before and immediately after the
      first treatment and after the treatment on the third month, using
      echocardiography, exercise stress testing, ambulatory ECG, right ventricular
      catheterization, cardiac enzymes (creatine kinase MB isoenzyme - CK-MB, troponin
      T) and the Minnesota Living with Heart Failure Questionnaire for quality of life.
      RESULTS: After the first treatment, left ventricular ejection fraction (LVEF),
      cardiac output, cardiac index (CI), pulmonary wedge pressure and life quality
      improved significantly (p<0.05); but, after the treatment on the third month,
      these parameters except PCWP returned to nearly baseline values. Additionally, a
      significant increase in the number of patients with ventricular premature beats
      and with troponin-T positivity was detected after the third month of treatment.
      CONCLUSION: The use of dobutamine in addition to conventional therapy in patients
      with DCM provided improvements in some systolic parameters and quality of life
      particularly after the first treatment. In the late period of the treatment,
      however, it was determined that these beneficial effects tended to disappear and
      harmful effects became more evident.

PMID- 12223322
TI  - [Surgical treatment of aortic coarctation in adults: mid-term results and effects
      on the systolic blood pressure].
AB  - OBJECTIVE: To evaluate the outcome and the systolic blood pressure changes after
      surgical treatment of aortic coarctation in adults. METHODS: Between February
      1995 and January 2001, 12 adult patients with a mean age of 29+/-10 years,
      underwent repair of aortic coarctation in our clinic. The diagnostic and
      operative data of these patients were retrospectively analyzed. Follow-up was
      complete in all hospital survivors. RESULTS: The mean systolic blood pressure of
      8 hypertensive patients decreased from 155+/-7 mmHg to 115+/-9 mmHg after
      surgical intervention. One patient with a dilated cardiomyopathy died one day
      after the operation due to an intractable ventricular fibrillation (mortality
      8.3%). Four patients had been operated for coexisting cardiovascular pathologies
      during a mean follow-up period of 32+/-26 months. CONCLUSION: Surgical treatment
      of aortic coarctation in adults can be safely performed with an acceptable
      mortality and morbidity, both resulting from coexisting cardiovascular disorders
      in our patient group. The systolic blood pressure may decrease significantly
      after the operation.

PMID- 12223324
TI  - [Evaluation of "admission index of insulin resistance (AIRI)" as an early stage
      risk predictor in nondiabetic acute coronary syndromes].
AB  - OBJECTIVE: Insulin resistance is a risk predictor for many cardiovascular
      diseases, but its effect on etiology and prognosis of diseases has not been
      clearly identified. In this study, we aimed to investigate whether admission
      index of insulin resistance (AIRI), recently and practically presented for
      determination of insulin resistance, could be a new risk predictor of early
      prognosis in nondiabetic acute coronary syndromes. METHODS: One hundred and sixty
      nondiabetic patients admitted to the intensive coronary care unit and underwent
      coronary angiography with the diagnosis of acute myocardial infarction (AMI)
      (Group I; 72 patients; mean age - 58+/-12 years) or unstable angina pectoris
      (UAP) (Group II; 88 patients; mean age 58+/-10 years) were included in the study.
      In all patients blood glucose and insulin levels were measured on admission and
      AIRI was calculated by the formula of "admission glucose level X insulin level /
      normal blood glucose level (5 mmol/L) X normal insulin level (5 mU/L)" for each
      patient. After determining the left ventricular ejection fraction (LVEF) and wall
      motion score index (LVWMSI) echocardiographically and calculating the Gensini
      score index from coronary angiography, the patients were followed up for major
      cardiac events (heart failure, atrial fibrillation, reinfarction, life
      threatening ventricular arrhythmias, atrio-ventricular block, need for
      revascularisation and mortality) for 30 days. RESULTS: AIRI was found higher in
      Group I (7.2+/-5.3 versus 5.2+/-4.4, p< 0.01) than in Group II. AIRI was
      positively correlated with Gensini score and LVWMSI (r=0.41, p<0.01 and r=0.48,
      p<0.001, respectively) and negatively correlated with LVEF (r=-0.37, p=0.001) in
      Group I. In addition, it was seen that positive correlation of AIRI with Gensini
      score (r=0.23, p=0.01) and LVWMSI (r=0.43, p=0.0001) in Group I persisted on
      multivariate regression analysis. Again, AIRI was significantly correlated with
      heart failure (r=0.42, p<0.0001), atrial fibrillation (r=0.35, p=0.002) and
      reinfarction (r=0.23, p=0.04) in Group I. Along with this, in multivariate
      regression analysis, it was correlated with heart failure (r=0.21, p<0.007),
      atrial fibrillation (r=0.18, p=0.01) and reinfarction (r=0.18, p=0.01). On the
      other hand, there was no significant correlation between AIRI and these
      parameters in Group II. CONCLUSION: AIRI can be used in early stage as a risk
      predictor to determine high-risk subgroups of nondiabetic patients presenting
      with AMI. Also AIRI, a parameter, which is practically calculated and easily
      used, is an independent risk factor detecting the extent of coronary artery
      disease and left ventricular dysfunction in patients with AMI.

PMID- 12223326
TI  - [Risk factor distribution according to the obesity degree in patients with
      coronary artery disease].
AB  - OBJECTIVE: World Health Organization and other international guide committees
      defined different obesity categories according to the body mass index (BMI) and
      waist circumferences. The purpose of our study was (i) to compare the dispersion
      of other coronary risk factors in patients with coronary artery disease (CAD)
      with different obesity categories that were defined according to the body mass
      index (BMI) and the waist circumference, (ii) to determine to which extent these
      cut-off values effect the dispersion of other coronary risk factors. METHODS: The
      study group included 617 consecutive subjects (516 male, mean age - 57.2+/-10.8
      years) who underwent their first angiography between January 2000 and May 2000
      and in whom significant coronary lesions were detected. The distribution of risk
      factors such as, age, smoking, hypertension, diabetes mellitus, high LDL-C, low
      HDL-C, total cholesterol/HDL-C ratio, triglycerides, family history of premature
      CAD was compared between overweight and obese cases defined according to BMI
      values. The same risk factors were compared among the cases grouped as action
      level 1 and action level 2 defined by the waist circumference. RESULTS: In male
      patients; smoking was found to be higher in overweight individuals than in obese
      cases (71% vs. 56%) (p<0.05). In female patients; the only difference was the
      ratio of total-C/HDL-C as being greater in obese group than overweight group
      (p<0.05). In male and female patients there was no significant difference between
      obese and overweight cases regarding the number of total risk factors. According
      to the waist circumference, in male patients, smoking was more prevalent in
      action level 1 group than in action level 2 group. In female patients risk
      factors prevalence was similar in both groups. CONCLUSION: In patients with CAD,
      the amount of total risk factors doesn't differ between overweight and obese
      cases and between patients with action level 1 and action level 2 of the waist
      circumference. These findings indicate the necessity of using the same secondary
      prevention approaches in patients with CAD and different levels of obesity.

PMID- 12223328
TI  - [Prognostic factors of mitral stenosis during pregnancy].
AB  - OBJECTIVE: To identify characteristics associated with complications during
      pregnancy in patients with mitral stenosis. METHODS: Thirty-seven pregnant women
      with mitral stenosis, followed-up from 1998 to 2001 were evaluated. Predictor
      variables were the mitral valve area (MVA) measured by echocardiogram and
      functional class (FC) before pregnancy according to NYHA criteria. Progression of
      functional class, thromboembolism, death, need in medical abortion, cardiac
      surgery or balloon mitral valvulotomy were accepted as maternal events.
      Fetal/neonatal events were determined as abortion, fetal or neonatal death,
      prematurity or low birth weight (p<2.500 g), and extended stay in the nursery or
      hospitalization in newborn intensive care unit. RESULTS: The mean +/- SD of age
      of the patients was 24.7+/-5.8 years. The eventful and uneventful patients were
      similar in age and percentage of first pregnancies. Of patients with an events
      occuring during gestational period, 37. 5% had class I functional capacity
      whereas 62.5% had class II/III (p=0.001). A clinical event was noted in 34 % of
      the patients with sinus rhythm and in all of patients with atrial fibrillation
      (p=0.007). The mean mitral valve area was 1.11+/-0.23 cm2 in the group with
      clinical event and 1.6+/-0.27 cm2 in the group without an event (p<0.001). The
      most frequently observed maternal complication was the worsening of the
      functional capacity and the most frequent fetal/neonatal complications were
      prematurity and low birth weight. Mitral valve area and functional capacity were
      found to be significantly related with maternal complications but not with the
      fetal/neonatal complications. CONCLUSION: In pregnant women with mitral stenosis,
      the MVA and the FC are strongly associated with maternal complications but not
      related to fetal/neonatal events.

PMID- 12223331
TI  - [The relationship between QT dispersion and risk factors of sudden death in
      hypertrophic cardiomyopathy].
AB  - OBJECTIVE: Several risk factors are established for prediction of sudden cardiac
      death caused by ventricular arrhythmias in patients with hypertrophic
      cardiomyopathy (HCM). QT dispersion (QTd) is thought to reflect the heterogeneity
      of ventricular repolarization. The relation of QTd with ventricular arrhythmias
      and sudden cardiac death has been shown by several studies. The aim of this study
      is to examine whether there is a relationship between QTd and established risk
      factors of sudden cardiac death in patients with HCM. METHODS: In the present
      study 48 patients with HCM and 30 normal subjects were studied. The patients with
      electrocardiographic changes that could affect QT interval measurements and those
      in whom QTd was calculated in less than 9 leads were excluded from the study. A
      family history of sudden death due to HCM, a history of ventricular fibrillation,
      nonsustained ventricular tachycardia on Holter monitoring and a history of
      recurrent syncope were accepted as risk factors for sudden cardiac death.
      RESULTS: QTd was significantly greater in patients with HCM than in normal
      controls (55+/-22 ms vs 34+/-13 ms, p<0.001). There was no significant difference
      in QTd between patients with and without risk factors (57+/-22 ms vs 53+/-20 ms,
      p>0.05). There was also no significant difference in QTd between patients with
      and without left ventricular outflow gradient p>30 mmHg (57+/-23 ms vs 53+/-19
      ms, p>0.05). CONCLUSION: Although QTd was significantly greater in patients with
      HCM than in normal controls, its relation to risk factors of sudden death could
      not be established.

PMID- 12223332
TI  - [Assessment of cases with syncope due to primary pulmonary hypertension].
AB  - Primary pulmonary hypertension is an uncommon disease. Its diagnosis is suspected
      after clinical examination however it can be made only after detailed evaluation
      of heart and lungs and exclusion of all etiologies for secondary pulmonary
      hypertension. Prognosis in general is poor but it ranges individually. In this
      article we aimed to examine this subject by interpreting a patient referred to
      our clinic for syncope and diagnosed as primary pulmonary hypertension.

PMID- 12223333
TI  - [Direct stent implantation: feasibility, advantages and disadvantages].
AB  - Coronary stent implantation was firstly performed as only a bail-out procedure
      for poor angioplasty results, but nowadays it has become a primary modality of
      coronary revascularization. The deployment of intracoronary stents during
      percutaneous transluminal coronary angioplasty has been shown in a number of
      clinical trials to provide additional benefits regarding the rate of restenosis
      and clinical outcome over angioplasty alone. Direct stent implantation is the
      term applied to the technique of coronary stent implantation without firstly
      preparing the way with balloon predilation. In simple lesion subsets, both
      initial success rate and restenosis rate are superior to conventional balloon
      angioplasty. There is a considerable potential advantage of direct stenting over
      conventional stenting with respect to savings in procedural time, contrast load,
      and fluoroscopy time. Because predilation is not employed, there is an additional
      saving on angioplasty balloons, and a more efficient and less usage of stents is
      possible by minimizing the dissection rate. Lesion selection plays a major role
      in the high success rates. Long, heavily calcified lesions, small vessels or
      lesions with excessive proximal tortuosity are not considered suitable for direct
      stenting. With additional experience and continued improvement in stent
      technology it seems likely that more patients will be potential candidates for
      direct stenting.

PMID- 12223334
TI  - [Electrophysiological mechanisms of atrial fibrillation].
AB  - The electrophysiological mechanism of atrial fibrillation (AF) has been the
      subject of interest for almost a hundred years. The mechanism that leads to the
      induction of atrial fibrillation can be a single automatic focus firing impulses
      with high rate (e.g. pulmonary vein) as well as macro- or more frequently micro
      re-entrant circuits. The focal mechanism has been recently shown to be
      responsible for at least a particular group of AF cases. Cellular and
      electrophysiological abnormalities such as partly depolarised cells, fibrosis,
      conduction abnormalities, shortening of the refractoriness and the increase in
      dispersion of refractoriness in the atrium can be the underlying factors for the
      genesis of atrial fibrillation. Factors such as the autonomic nervous system,
      aging, enlargement of the atria can modulate these electrophysiological features.
      AF can be maintained in the existence of particular conditions and AF itself
      leads to some changes in the atrium that are thought to be the base of
      perpetuation of fibrillation in the atria. These changes in the atrial
      electrophysiology and anatomy are called AF-induced atrial remodeling. Whatever
      it is the triggering mechanism for AF, "multiple wavelet re-entry" has been
      widely accepted to be the maintaining mechanism of AF. Finally, it can be
      considered that we are facing the different types of AF that can be induced with
      different mechanisms, that need special conditions to perpetuate and maintain,
      but present with similar findings in the electrocardiogram.

PMID- 12223335
TI  - [Toward the perfect heart-lung machine].

PMID- 12223336
TI  - A case of myocardial ischaemia induced by 5-fluorouracil.

PMID- 12223337
TI  - [The combined use of sildenafil with epoprostenol in a patient with primary
      pulmonary hypertension].

PMID- 12223338
TI  - On medical journals, history and art: two comments on JAMA 2001 covers. Is
      prejudice a curable attitude of mind or a hopeless case?

PMID- 12223339
TI  - [A few words on Eugene Delacroix's picture, "Botzaris surprises the Turkish camp
      and falls fatally wounded"].

PMID- 12223340
TI  - [Original image: severe and widespread coronary ectasia].

PMID- 12223341
TI  - Aging and neural control of the GI tract. II. Neural control of the aging gut:
      can an old dog learn new tricks?
AB  - There has been a dramatic increase in funding available for aging research,
      primarily due to the fact that answers to questions on aging are likely to have a
      major impact on the well-being and healthy aging of the world's population for
      decades to come. The incidence of certain gastrointestinal problems, such as
      dysphagia and constipation, increases dramatically with age. Changes in
      gastrointestinal neuromuscular function with aging have been demonstrated in both
      human and animal models of aging. This article focuses on recent advances in our
      knowledge of the effects of aging on gastrointestinal function, treatment
      options, and future opportunities for research.

PMID- 12223342
TI  - The epithelial cell cytoskeleton and intracellular trafficking. V. Polarized
      compartmentalization of antigen processing and Toll-like receptor signaling in
      intestinal epithelial cells.
AB  - The intestinal epithelial cell (IEC) is exposed at the apical surface to a high
      concentration of foreign antigen and bacterial products capable of triggering
      inflammatory responses. Complex intracellular pathways of antigen trafficking and
      the polarized expression of immunologically active receptors provide additional
      means to regulate the inflammatory pathways in these cells. In the case of human
      leukocyte antigen (HLA) class II heterodimers, surface expression is highly
      restricted to the basolateral surface, and this also appears to be the case for
      Toll-like receptor 5 (TLR5) on polarized T84 human colon cancer cells. Processing
      of soluble antigen via HLA class II in IEC can occur following internalization
      from the apical surface but is highly inefficient. In addition, certain bacteria
      can facilitate the transport of flagellin (the ligand for TLR5) across an intact
      epithelium. Disruption of the tight junctions between IECs, allowing direct
      access of antigen and flagellin to the basolateral surface of the cell,
      dramatically affects the functional outcome HLA class II and TLR5 pathways.

PMID- 12223343
TI  - Heparin-binding EGF-like growth factor gene transcription regulated by Cdx2 in
      the intestinal epithelium.
AB  - Development and differentiation of the intestinal epithelium appear to be
      regulated by various growth factors. Using cDNA microarrays, we identified
      heparin-binding EGF-like growth factor (HB-EGF) as one of the genes induced by
      intestinal-specific transcription factor Cdx2 in an intestinal undifferentiated
      rat cell line, intestinal epithelial cell (IEC)-6. Both Cdx2 and HB-EGF
      stimulated cell proliferation and migration, and their effects were inhibited
      partially by an EGF receptor-specific tyrosine kinase inhibitor, PD-153035. HB
      EGF may function as one of the mediators of Cdx2 and may be associated with the
      proliferation and migration in the intestinal epithelium. The Cdx2 protein can
      bind to the Cdx2-binding element of the HB-EGF gene. Reporter gene analyses
      showed that the HB-EGF gene promoter is Cdx2 responsive and that the activity of
      the promoter in the IEC-6 cells depends on the number of consensus Cdx2-binding
      site-like sequences. These data indicate that HB-EGF gene expression can be
      regulated by Cdx2 and serves to mediate the control of Cdx2 of the proliferation
      and migration of IEC-6 cells.

PMID- 12223344
TI  - A phosphorylated phloretin derivative. Synthesis and effect on intestinal Na(+)
      dependent phosphate absorption.
AB  - 2'-Phosphophloretin (2'-PP), a phosphorylated derivative of the plant chalcone,
      was synthesized. The effect of 2'-PP, on Na(+)-dependent phosphate uptake into
      intestinal brush-border membrane vesicles (BBMV) isolated from rabbit and rat
      duodenum and jejunum was examined. 2'-PP decreased Na(+)-dependent phosphate
      uptake into rabbit BBMV with an IC(50) of 55 nM and into rat BBMV with an IC(50)
      of 58 nM. 2'-PP did not affect Na(+)-dependent glucose, Na(+)-dependent sulfate,
      or Na(+)-dependent alanine uptake by rabbit intestinal BBMVs. 2'-PP inhibition of
      rabbit intestinal BBMV Na(+)-dependent phosphate uptake was sensitive to external
      phosphate concentration, suggesting that 2'-PP inhibition of Na(+)-dependent
      phosphate uptake was competitive with respect to phosphate. Binding of [(3)H]2'
      PP to rabbit intestinal BBMV was examined. Binding of [(3)H]2'-PP was Na(+)
      dependent with a K(0.5) for Na(+)(Na(+) concentration for 50% 2'-PP binding) of
      30 mM. The apparent K(s) for Na(+)-dependent [(3)H]2'-PP binding to rabbit BBMVs
      was 58 nM in agreement with the IC(50) for 2'-PP inhibition of Na(+)-dependent
      phosphate uptake. These results indicate that 2'-PP bound to rabbit or rat
      intestinal BBMV Na(+)-phosphate cotransporter and inhibited Na(+)-dependent
      phosphate uptake. In rats treated with 2'-PP by daily gavage, the effect of 2'-PP
      on serum phosphate, serum glucose, and serum calcium was examined. In a
      concentration-dependent manner, 2'-PP reduced serum phosphate by 45% 1 wk after
      starting treatment. 2'-PP did not alter serum calcium or serum glucose. The
      apparent IC(50) for 2'-PP in vivo was 3 microM.

PMID- 12223345
TI  - Molecular evidence for a glycine-gated chloride channel in macrophages and
      leukocytes.
AB  - Recent studies have demonstrated that glycine blunts the response of Kupffer
      cells to endotoxin. Based on pharmacological evidence, it was hypothesized that
      Kupffer cells and other macrophages contain a glycine-gated chloride channel
      similar to the glycine receptor expressed in neuronal tissues. Moreover, glycine
      stimulates influx of radiolabeled chloride in Kupffer cells in a dose-dependent
      manner. RT-PCR was used to identify mRNA of both alpha- and beta-subunits of the
      glycine receptor in rat Kupffer cells, peritoneal neutrophils, and splenic and
      alveolar macrophages, similar to the sequence generated from rat spinal cord.
      Importantly, the sequence of the cloned Kupffer cell glycine receptor fragment
      for the beta-subunit was >95% homologous with the receptor from the spinal cord.
      Membranes of these cells also contain a protein that is immunoreactive with
      antibodies against the glycine-gated chloride channel. These data demonstrate
      that Kupffer cells, as well as other macrophages and leukocytes, express mRNA and
      protein for a glycine-gated chloride channel with both molecular and
      pharmacological properties similar to the channel expressed in the central
      nervous system.

PMID- 12223346
TI  - Transforming growth factor-beta 1 signaling contributes to Caco-2 cell growth
      inhibition induced by 1,25(OH)(2)D(3).
AB  - Growth of Caco-2 and many cancer cells is inhibited by 1,25(OH)(2)D(3). Whereas
      TGF-beta 1 inhibits normal colonic epithelial cell growth, most human colon
      cancer-derived cells, including Caco-2 and SW480 cells, are resistant to it. The
      mechanisms underlying these antiproliferative actions and resistance to TGF-beta
      growth inhibition are largely unknown. We observed that 1,25-dihydroxyvitamin
      D(3) [1,25(OH)(2)D(3)] sensitized Caco-2 and SW480 cells to TGF-beta 1 growth
      inhibitory effects. Versus 1,25(OH)(2)D(3) alone, the combination of
      1,25(OH)(2)D(3) and TGF-beta 1 significantly reduced cell numbers. Also, the
      amount of active TGF-beta 1 was increased (~4-fold) by this secosteroid in
      conditioned media from Caco-2 cells. The 1,25(OH)(2)D(3) increased the expression
      of IGF-II receptors (IGF-IIR), which facilitated activation of latent TGF-beta 1,
      and was found to activate TGF-beta signaling in Caco-2 cells. By using
      neutralizing antibodies to human TGF-beta 1, we showed that this cytokine
      contributes to secosteroid-induced inhibition of Caco-2 cell growth. Also,
      1,25(OH)(2)D(3) was found to enhance the type I TGF-beta receptor mRNA and
      protein abundance in Caco-2 cells. Whereas the 1,25(OH)(2)D(3)-induced
      sensitization of Caco-2 cells to TGF-beta 1 was IGF-IIR independent, the type I
      TGF-beta 1 receptor was required for this sensitization. Thus 1,25(OH)(2)D(3)
      treatment of Caco-2 cells results in activation of latent TGF-beta 1, facilitated
      by the enhanced expression of IGF-IIR by this secosteroid. Also, 1,25(OH)(2)D(3)
      sensitized Caco-2 cells to growth inhibitory effects of TGF-beta 1, contributing
      to the inhibition of Caco-2 cell growth by this secosteroid.

PMID- 12223347
TI  - Mesenchymal IGF-I overexpression: paracrine effects in the intestine, distinct
      from endocrine actions.
AB  - Local IGF-I expression is frequently increased in intestinal mesenchyme during
      adaptive growth of intestinal epithelium, but paracrine growth effects of IGF-I
      in vivo are not defined. We tested whether overexpression of IGF-I in intestinal
      mesenchyme increases epithelial growth and if effects are distinct from known
      effects of circulating IGF-I. SMP8-IGF-I-transgenic (TG) mice overexpress IGF-I
      driven by an alpha-smooth muscle actin promoter. Mucosal and muscularis growth
      were assessed in the jejunum, ileum, and colon of SMP8-IGF-I-TG mice and wild
      type littermates. Abundance of the SMP8-IGF-I transgene and IGF binding protein
      (IGFBP)-3 and -5 mRNAs was determined. Mucosal growth was increased in SMP8-IGF-I
      TG ileum but not jejunum or colon; muscularis growth was increased throughout the
      bowel. IGFBP-5 mRNA was increased in SMP8-IGF-I-TG jejunum and ileum and was
      specifically upregulated in ileal lamina propria. Overexpression of IGF-I in
      intestinal mesenchymal cells has preferential paracrine effects on the ileal
      mucosal epithelium and autocrine effects on the muscularis throughout the bowel.
      Locally expressed IGF-I has distinct actions on IGFBP expression compared with
      circulating IGF-I.

PMID- 12223348
TI  - Measuring esophageal distension by high-frequency intraluminal ultrasound probe.
AB  - Distension of the esophagus can cause heartburn and chest pain; however, none of
      the available techniques to study the esophagus measure esophageal distension. We
      evaluated the technique of high-frequency intraluminal ultrasound probe (HFIUS)
      to measure the esophageal cross-sectional area (CSA) during gastroesophageal
      reflux (GER). The following methods were used: 1) the CSA of agarose gel tubes of
      known dimensions were measured using ultrasound probes; 2) seven normal subjects
      were studied to evaluate the esophageal CSA during different bolus volumes (1, 5,
      10, 15, and 20 ml) of water swallows (WS); and 3) simultaneous pressures, pH, and
      ultrasound images of the esophagus were recorded in healthy subjects. In vitro
      studies showed that the HFIUS measured the CSA of the tubes accurately. The
      maximal CSA of the distal esophagus during WS with boluses of 1, 5, 10, 15, and
      20 ml were 54, 101, 175, 235, and 246 mm(2), respectively. Esophageal contents
      during 62 episodes of transient lower esophageal sphincter relaxations, 29 pH
      positive, and 33 pH negative GER episodes revealed that reflux of air into the
      esophagus occurred more frequently than liquid. The median CSA and estimated
      diameter of the esophagus during liquid GER was 44.1 mm(2) and 7.5 mm,
      respectively. We conclude that HFIUS is a valid technique to measure the CSA of
      the esophagus in vivo during GER. Distension of the esophagus during
      physiological GER is relatively small.

PMID- 12223349
TI  - Secretin regulates paracellular permeability in canine gastric monolayers by a
      Src kinase-dependent pathway.
AB  - Previous studies found that epidermal growth factor (EGF) decreased paracellular
      permeability in gastric mucosa, but the other physiological regulators and the
      molecular mechanisms mediating these responses remain undefined. We investigated
      the role of secretin and Src in regulating paracellular permeability because
      secretin regulates gastric chief cell function and Src mediates events involving
      the cytoskeletal-membrane interface, respectively. Confluent monolayers were
      formed from canine gastric epithelial cells in short-term culture on Transwell
      filter inserts. Resistance was monitored in the presence of secretin with or
      without specific kinase inhibitors. Tyrosine phosphorylation of Src at Tyr(416)
      was measured with a site-specific phosphotyrosine antibody. Basolateral, but not
      apical, secretin at concentrations from 1 to 100 nM dose dependently increased
      resistance; this response was rapid and sustained over hours. PP2 (10 microM), a
      selective Src tyrosine kinase inhibitor, but not the inactive isomer PP3,
      abolished the increase in resistance by secretin but only modestly attenuated
      apical EGF effects. AG-1478 (100 nM), a specific EGF receptor tyrosine kinase
      inhibitor, attenuated the resistance increase to EGF but not secretin. Secretin,
      but not EGF, induced tyrosine phosphorylation of Src at Tyr(416) in a dose
      dependent fashion, with the maximal response observed at 1 min. PP2, but not PP3,
      dramatically inhibited this tyrosine phosphorylation. Secretin increases
      paracellular resistance in gastric mucosa through a Src-mediated pathway, while
      the effect of EGF is Src independent. Src appears to mediate the physiological
      effects of this G(s)-coupled receptor in primary epithelial cells.

PMID- 12223350
TI  - Fat malabsorption in essential fatty acid-deficient mice is not due to impaired
      bile formation.
AB  - Essential fatty acid (EFA) deficiency induces fat malabsorption, but the
      pathophysiological mechanism is unknown. Bile salts (BS) and EFA-rich biliary
      phospholipids affect dietary fat solubilization and chylomicron formation,
      respectively. We investigated whether altered biliary BS and/or phospholipid
      secretion mediate EFA deficiency-induced fat malabsorption in mice. Free virus
      breed (FVB) mice received EFA-containing (EFA(+)) or EFA-deficient (EFA(-)) chow
      for 8 wk. Subsequently, fat absorption, bile flow, and bile composition were
      determined. Identical dietary experiments were performed in multidrug resistance
      gene-2-deficient [Mdr2((-/-))] mice, secreting phospholipid-free bile. After 8
      wk, EFA(-)-fed wild-type [Mdr2((+/+))] and Mdr2((-/-)) mice were markedly EFA
      deficient [plasma triene (20:3n-9)-to-tetraene (20:4n-6) ratio >0.2]. Fat
      absorption decreased (70.1 +/- 4.2 vs. 99.1 +/- 0.3%, P < 0.001), but bile flow
      and biliary BS secretion increased in EFA(-) mice compared with EFA(+) controls
      (4.87 +/- 0.36 vs. 2.87 +/- 0.29 microl x min(-1) x 100 g body wt(-1), P < 0.001,
      and 252 +/- 30 vs. 145 +/- 20 nmol x min(-1) x 100 g body wt(-1), P < 0.001,
      respectively). BS composition was similar in EFA(+)- and EFA(-)-fed mice. Similar
      to EFA(-) Mdr2((+/+)) mice, EFA(-) Mdr2((-/-)) mice developed fat malabsorption
      associated with twofold increase in bile flow and BS secretion. Fat malabsorption
      in EFA(-) mice is not due to impaired biliary BS or phospholipid secretion. We
      hypothesize that EFA deficiency affects intracellular processing of dietary fat
      by enterocytes.

PMID- 12223351
TI  - PKC-zeta prevents oxidant-induced iNOS upregulation and protects the microtubules
      and gut barrier integrity.
AB  - Using intestinal (Caco-2) monolayers, we reported that inducible nitric oxide
      synthase (iNOS) activation is key to oxidant-induced barrier disruption and that
      EGF protects against this injury. PKC-zeta was required for protection. We thus
      hypothesized that PKC-zeta activation and iNOS inactivation are key in EGF
      protection. Wild-type (WT) Caco-2 cells were exposed to H(2)O(2) (0.5 mM) +/- EGF
      or PKC modulators. Other cells were transfected to overexpress PKC-zeta or to
      inhibit it and then pretreated with EGF or a PKC activator (OAG) before oxidant.
      Relative to WT cells exposed to oxidant, pretreatment with EGF protected
      monolayers by 1) increasing PKC-zeta activity; 2) decreasing iNOS activity and
      protein, NO levels, oxidative stress, tubulin oxidation, and nitration); 3)
      increasing polymerized tubulin; 4) maintaining the cytoarchitecture of
      microtubules; and 5) enhancing barrier integrity. Relative to WT cells exposed to
      oxidant, transfected cells overexpressing PKC-zeta (+2.9-fold) were protected as
      indicated by decreases in all measures of iNOS-driven pathways and enhanced
      stability of microtubules and barrier function. Overexpression-induced inhibition
      of iNOS was OAG independent, but EGF potentiated this protection. Antisense
      inhibition of PKC-zeta (-95%) prevented all measures of EGF protection against
      iNOS upregulation. Thus EGF protects against oxidative disruption of the
      intestinal barrier by stabilizing the cytoskeleton in large part through the
      activation of PKC-zeta and downregulation of iNOS. Activation of PKC-zeta is by
      itself required for cellular protection against oxidative stress of iNOS. We have
      thus discovered novel biologic functions, suppression of the iNOS-driven
      reactions and cytoskeletal oxidation, among the atypical PKC isoforms.

PMID- 12223352
TI  - Interferon-gamma activates EGF receptor and increases TGF-alpha in T84 cells:
      implications for chloride secretion.
AB  - IFN-gamma inhibits intestinal Cl(-) secretion, in part via downregulation of CFTR
      and Na(+)-K(+)-ATPase activity and expression, but the proximal signaling events
      were unknown. We have shown that transforming growth factor-alpha (TGF-alpha)
      inhibits calcium-activated Cl(-) secretion, and effects of IFN-gamma in other
      systems are mediated via EGF family members. We tested whether IFN-gamma inhibits
      Cl(-) secretion via EGF receptor (EGFr) activation. IFN-gamma increased tyrosine
      phosphorylation in T84 cells at 24 h, including the EGFr. IFN-gamma also
      increased cell-associated pro-TGF-alpha, as well as free TGF-alpha in the bathing
      media. However, whereas IFN-gamma significantly inhibited carbachol-induced Cl(-)
      secretion, neither neutralizing antibodies to TGF-alpha nor an EGFr inhibitor (1
      microM tyrphostin AG 1478) were able to reverse this inhibitory effect. AG 1478
      also failed to reverse IFN-gamma-induced tyrosine phosphorylation of the EGFr,
      but receptor phosphorylation was attenuated by both the neutralizing antibody to
      TGF-alpha and PP2, a Src kinase inhibitor. Moreover, PP2 reversed the inhibitory
      effect of IFN-gamma on Cl(-) secretion. In total, our findings suggest an
      increase in functional TGF-alpha and activation of the EGFr in response to IFN
      gamma. The release of TGF-alpha and intracellular Src activation likely combine
      to mediate EGFr phosphorylation, but only Src appears to contribute to the
      inhibition of transport. Nevertheless, because TGF-alpha plays a role in
      restitution and repair of the intestinal epithelium after injury, we speculate
      that these findings reflect a feedback loop whereby IFN-gamma modulates the
      extent of cytokine-induced intestinal damage.

PMID- 12223353
TI  - Regulatory volume decrease in human esophageal epithelial cells.
AB  - In vivo human esophageal epithelial cells are regularly exposed to hyposmolal
      stress. This stress, however, only becomes destructive when the surface
      epithelial cell (barrier) layers are breached and there is contact of the
      hyposmolal solution with the basolateral cell membranes. The present
      investigation was designed to examine the effects of hyposmolal stress in the
      latter circumstance using as a model for human esophageal epithelial cells the
      noncancer-derived HET-1A cell line. Cell volume and the response to hyposmolal
      stress in suspensions of HET-1A cells were determined by cell passage through a
      Coulter Counter Multisizer II. HET-1A cells behaved as osmometers over the range
      of 280 to 118 mosmol/kg H(2)O with rapid increases in cell volume < or = 15-20%
      above baseline. Following swelling, the cells exhibited regulatory volume
      decrease (RVD), restoring baseline volume within 30 min, despite continued
      hyposmolal stress. With the use of pharmacologic agents and ion substitutions,
      RVD appeared to result from rapid activation of parallel K(+) and Cl(-)
      conductance pathways and this was subsequently joined by activation of a KCl
      cotransporter. Exposure to hyposmolal stress in an acidic environment, pH 6.6,
      inhibited, but did not abolish, RVD. These data indicate that human esophageal
      epithelial cells can protect against hyposmolal stress by RVD and that the
      redundancy in mechanisms may, to some extent, serve as added protection in
      patients with reflux disease when hyposmolal stress may occur in an acidic
      environment.

PMID- 12223354
TI  - Primary sensory neurons: a common final pathway for inflammation in experimental
      pancreatitis in rats.
AB  - We hypothesized that neurogenic inflammation is a common final pathway for
      parenchymal inflammation in pancreatitis and evaluated the role of primary
      sensory neurons in secretagogue-induced and obstructive pancreatitis. Neonatal
      rats received either the primary sensory neuron-denervating agent capsaicin (50
      mg/kg s.c.) or vehicle. At 8 wk of age, pancreatitis was produced by six hourly
      injections of caerulein (50 microg/kg i.p.) or by common pancreaticobiliary duct
      ligation (CPBDL). The severity of pancreatitis was assessed by serum amylase,
      pancreatic myeloperoxidase (MPO) activity, histological grading, pancreatic
      plasma extravasation, and wet-to-dry weight ratio. Caerulein significantly
      increased MPO activity and wet-to-dry weight ratio, produced histological
      evidence of edematous pancreatitis, induced plasma extravasation, and caused
      hyperamylasemia. CPBDL increased MPO activity and produced histological evidence
      of pancreatitis. Neonatal capsaicin administration significantly reduced tissue
      MPO levels, histological severity scores, and wet-to-dry weight ratio and
      abolished plasma extravasation. These results demonstrate that primary sensory
      neurons play a significant role in the inflammatory cascade in experimental
      pancreatitis and appear to constitute a common final pathway for pancreatic
      parenchymal inflammation.

PMID- 12223355
TI  - Tumor necrosis factor-alpha-associated lysosomal permeabilization is cathepsin B
      dependent.
AB  - Cathepsin B (Cat B) is released from lysososomes during tumor necrosis factor
      alpha (TNF-alpha) cytotoxic signaling in hepatocytes and contributes to cell
      death. Sphingosine has recently been implicated in lysosomal permeabilization and
      is increased in the liver by TNF-alpha. Thus the aims of this study were to
      examine the mechanisms involved in TNF-alpha-associated lysosomal
      permeabilization, especially the role of sphingosine. Confocal microscopy
      demonstrated Cat B-green fluorescent protein and LysoTracker Red were both
      released from lysosomes after treatment of McNtcp.24 cells with TNF
      alpha/actinomycin D, a finding compatible with lysosomal destabilization. In
      contrast, endosomes labeled with Texas Red dextran remained intact, suggesting
      lysosomes were specifically targeted for permeabilization. LysoTracker Red was
      released from lysosomes in hepatocytes treated with TNF-alpha or sphingosine in
      Cat B(+/+) but not Cat B(-/-) hepatocytes, as assessed by a fluorescence-based
      assay. With the use of a calcein release assay in isolated lysosomes, sphingosine
      permeabilized liver lysosomes isolated from Cat B(+/+) but not Cat B(-/-) liver.
      C(6) ceramide did not permeabilize lysosomes. In conclusion, these data implicate
      a sphingosine-Cat B interaction inducing lysosomal destabilization during TNF
      alpha cytotoxic signaling.

PMID- 12223356
TI  - Prevention of hepatic ischemia-reperfusion injury by green tea extract.
AB  - These experiments were designed to determine whether green tea extract (GTE),
      which contains polyphenolic free radical scavengers, prevents ischemia
      reperfusion injury to the liver. Rats were fed a powdered diet containing 0-0.3%
      GTE starting 5 days before hepatic warm ischemia and reperfusion. Free radicals
      in bile were trapped with the spin-trapping reagent alpha-(4-pyridyl-1-oxide)-N
      tert-butylnitrone (4-POBN) and measured using electron spin resonance
      spectroscopy. Hepatic ischemia-reperfusion increased transaminase release and
      caused pathological changes including focal necrosis and hepatic leukocyte
      infiltration in the liver. Transaminase release was diminished by over 85% and
      pathological changes were almost totally blocked by 0.1% dietary GTE. Ischemia
      reperfusion increased 4-POBN/radical adducts in bile nearly twofold, an effect
      largely blocked by GTE. Epicatechin, one of the major green tea polyphenols, gave
      similar protection as GTE. In addition, hepatic ischemia-reperfusion activated NF
      kappa B and increased TNF-alpha mRNA and protein expression. These effects were
      all blocked by GTE. Taken together, these results demonstrate that GTE scavenges
      free radicals in the liver after ischemiareoxygenation, thus preventing formation
      of toxic cytokines. Therefore, GTE could prove to be effective in decreasing
      hepatic injury in disease states where ischemia-reperfusion occurs.

PMID- 12223357
TI  - The transcytosis of divalent metal transporter 1 and apo-transferrin during iron
      uptake in intestinal epithelium.
AB  - Caco-2 cells grown in bicameral chambers are a model system to study intestinal
      iron absorption. Caco-2 cells exhibit constitutive transport of iron from the
      apical (luminal) chamber to the basal (serosal) chamber that is enhanced by apo
      transferrin in the basal chamber, with the apo-transferrin undergoing endocytosis
      to the apical portion of the cell. With the addition of iron to the apical
      surface, divalent metal transporter 1 (DMT1) on the brush-border membrane (BBM)
      undergoes endocytosis. These findings suggest that in Caco-2 cells DMT1 and apo
      transferrin may cooperate in iron transport through transcytosis. To prove this
      hypothesis, we determined by confocal microscopy that, after addition of iron to
      the apical chamber, DMT1 from the BBM and Texas red apo-transferrin from the
      basal chamber colocalized in a perinuclear compartment. Colocalization was also
      observed by isolating endosomes from Caco-2 cells after ingestion of ultra-small
      paramagnetic particles from either the basal or apical chamber. The isolated
      endosomes contained both transferrin and DMT1 independent of the chamber from
      which the paramagnetic particles were endocytosed. These findings suggest that
      iron transport across intestinal epithelia may be mediated by transcytosis.

PMID- 12223358
TI  - Region-specific adaptation of apical Na/H exchangers after extensive proximal
      small bowel resection.
AB  - After massive small bowel resection (MSBR), the remnant small intestine adapts to
      restore Na absorptive function. The possibility that this occurs through
      increases in cellular Na absorptive capacity was examined by assessing the
      regional effects of 50% proximal MSBR on the function and expression of the
      apical membrane Na/H exchangers (NHEs) NHE2 and NHE3. Morphometric analysis
      confirmed adaptive changes consistent with villus hypertrophy, particularly
      distal to the anastomosis. Villus epithelium prepared by light mucosal scrapings
      from 2-wk-postresected and -posttransected control rats exhibited comparable
      brush-border hydrolase activities, total cell protein per DNA, and villin
      expression but increased basolateral Na-K-ATPase activity. Parallel increases of
      two- to threefold in protein and mRNA abundance of NHE2 and NHE3 were observed
      only in ileal regions distal to the anastomosis of resected rats. Basolateral
      NHE1 expression was unchanged. After 80% resection, increases in NHE2 and NHE3
      became evident in proximal colon. We conclude that increased enterocyte
      expression and function of apical membrane NHEs in regions distal to the
      anastomosis play a role in the adaptive process after MSBR. The increased luminal
      Na load to distal bowel regions after proximal resection may stimulate increases
      in apical membrane NHE gene transcription and protein expression.

PMID- 12223359
TI  - Ammonia-induced apoptosis is accelerated at higher pH in gastric surface mucous
      cells.
AB  - Gastric luminal ammonia produced by Helicobacter pylori has been shown to cause
      gastric mucosal injury. This study was conducted to examine the mechanisms by
      which gastric luminal ammonia causes apoptosis of gastric epithelial cells.
      Monolayers of GSM06 cells, developed from murine gastric surface mucous cells,
      were cultured in the absence or presence of 10-30 mM NH(4)Cl at ambient pH of
      5.0, 6.0, and 7.0. In the presence of luminal NH(4)Cl, GSM06 cells showed 1) cell
      shrinkage and nuclear chromatin condensation, 2) DNA fragmentation into
      oligonucleosomes, 3) leakage of cytochrome c into cytosolic fraction without
      affecting bax expression, and 4) increases in activity of caspases-3 and -9.
      These changes were accentuated when the cells were cultured at pH 7.0. In the
      absence of NH(4)Cl, none of these changes was detected at any pH examined. These
      results suggest that gastric luminal ammonia, at concentrations detected in H.
      pylori-infected subjects, induces apoptosis of gastric epithelial cells by
      release of cytochrome c from mitochondria, followed by activation of caspases-9
      and -3, especially at higher ambient pH.

PMID- 12223360
TI  - Intestinal digestive resistance of immunodominant gliadin peptides.
AB  - Two recently identified immunodominant epitopes from alpha-gliadin account for
      most of the stimulatory activity of dietary gluten on intestinal and peripheral T
      lymphocytes in patients with celiac sprue. The proteolytic kinetics of peptides
      containing these epitopes were analyzed in vitro using soluble proteases from
      bovine and porcine pancreas and brush-border membrane vesicles from adult rat
      intestine. We showed that these proline-glutamine-rich epitopes are exceptionally
      resistant to enzymatic processing. Moreover, as estimated from the residual
      peptide structure and confirmed by exogenous peptidase supplementation,
      dipeptidyl peptidase IV and dipeptidyl carboxypeptidase I were identified as the
      rate-limiting enzymes in the digestive breakdown of these peptides. A similar
      conclusion also emerged from analogous studies with brush-border membrane from a
      human intestinal biopsy. Supplementation of rat brush-border membrane with trace
      quantities of a bacterial prolyl endopeptidase led to the rapid destruction of
      the immunodominant epitopes in these peptides. These results suggest a possible
      enzyme therapy strategy for celiac sprue, for which the only current therapeutic
      option is strict exclusion of gluten-containing food.

PMID- 12223361
TI  - ClC-2 in guinea pig colon: mRNA, immunolabeling, and functional evidence for
      surface epithelium localization.
AB  - The principal function of the colon in fluid homeostasis is the absorption of
      NaCl and water. Apical membrane Na(+) channels, Na(+)/H(+) and Cl(-)/HCO
      exchangers, have all been postulated to mediate NaCl entry into colonocytes. The
      identity of the basolateral exit pathway for Cl(-) is unknown. We have previously
      demonstrated the presence of the ClC-2 transcript in the guinea pig intestine.
      Now we explore in more detail, the tissue and cellular distribution of chloride
      channel ClC-2 in the distal colon by in situ hybridization and
      immunohistochemistry. The patch-clamp technique was used to characterize Cl(-)
      currents in isolated surface epithelial cells from guinea pig distal colon and
      these were compared with those mediated by recombinant guinea pig (gp)ClC-2. ClC
      2 mRNA and protein were found in the surface epithelium of the distal colon.
      Immunolocalization revealed that, in addition to some intracellular labeling, ClC
      2 was present in the basolateral membranes but absent from the apical pole of
      colonocytes. Isolated surface epithelial cells exhibited hyperpolarization
      activated chloride currents showing a Cl(-) > I(-) permeability and Cd(2+)
      sensitivity. These characteristics, as well as some details of the kinetics of
      activation and deactivation, were very similar to those of recombinant gpClC-2
      measured in parallel experiments. The presence of active ClC-2 type currents in
      surface colonic epithelium, coupled to a basolateral location for ClC-2 in the
      distal colon, suggests a role for ClC-2 channel in mediating basolateral membrane
      exit of Cl(-) as an essential step in a NaCl absorption process.

PMID- 12223362
TI  - Device malfunction in endovascular treatment of intracranial aneurysms: shared
      responsibilities of physician and manufacturer.

PMID- 12223363
TI  - Apparent diffusion coefficient and hematoma: "dose-dependent" relationship
      between hemorrhage and edema.

PMID- 12223364
TI  - Technical problems associated with new designs of Guglielmi detachable coils.
AB  - BACKGROUND AND PURPOSE: Recently, we experienced several technical problems that
      were directly related to new designs of Guglielmi detachable coils (GDCs). We
      herein present cases involving those problems and propose probable causes.
      METHODS: We reviewed the clinical and angiographic data of 269 consecutive
      patients with intracranial aneurysms who had been treated with GDCs between May
      1996 and October 2001. We focused on newly encountered technical problems:
      spontaneous premature coil detachment, backward slipping of the coil into the
      microcatheter lumen after detachment, and undesirable detachment of the coils at
      the parent artery. The occurrence and clinical consequences of the problems were
      investigated before and after the introduction of a new GDC (SynerG) design.
      Additionally, to confirm the potential causal relationship, in vitro observations
      and simulation tests were performed. RESULTS: Of the 269 patients, 69 underwent
      embolization between March and October of 2001. Among those, we encountered
      technical problems in 10 (14.5%) cases. The overall number of events was 12,
      including spontaneous detachment (n = 5), backward slipping of the coil into the
      microcatheter lumen after detachment (n = 4), and undesirable coil detachment
      with a segment of the coil remaining at the parent artery (n = 3). No similar
      problems occurred among the 200 patients treated during the period between May
      1996 and February 2001, when the new design coil had not yet been introduced. In
      vitro observations suggested that the long and stiff segment of the SynerG coil,
      especially the SR type, was a highly probable cause of these technical problems.
      CONCLUSION: Our clinical experience showed a high incidence of technical
      problems, and in vitro observations suggested that the new GDC designs could be
      responsible for them. For safe aneurysm treatment, details of embolization
      techniques should be modified.

PMID- 12223365
TI  - Marker alignment for Guglielmi detachable coil embolization: practical
      considerations.
AB  - BACKGROUND AND PURPOSE: Aneurysm embolization is not without risk: numerous
      technical aspects are considered before, during, and after the procedure. The
      purpose of this study was to show the position of the detachment zone of a
      Guglielmi detachable coil (GDC) with respect to the catheter tip for various
      microcatheters and marker alignments. METHODS: Six types of commonly used
      microcatheters were tested (Excel-14, Excelsior, FasTracker-10, Prowler-10,
      Prowler-14, and Rebar-14). First, the catheter markers and the distance from the
      catheter tip to the distal end of the proximal and distal markers of each
      catheter were compared. Second, the coil maker was aligned with the catheter
      marker. Third, the distal 3 cm of the microcatheter was modified by random
      shaping, with or without steaming. Last, marker alignment was tested with
      resterilized microcatheters (ethylene oxide gas sterilization). RESULTS: The
      length of the catheter marker and the distance between the catheter tip and the
      distal end of the proximal and distal catheter markers varied among the
      microcatheters. Sometimes, they varied even within the same microcatheter type.
      When a GDC was advanced until the proximal end of the marker on the delivery wire
      was exactly distal to the proximal catheter marker, the coil detachment zone was
      positioned at approximately 1.0 to 1.5 mm outside the catheter tip. Steaming or
      shaping of the distal 3 cm of the microcatheters resulted in the GDCs protruding
      more from the catheter tip. Resterilization also had an effect of marker distance
      shortening. Microcatheters were easily stretched by usual handling, such as
      removing a shaping mandrel from the catheter tip. CONCLUSION: Our study shows
      that proper marker alignment is influenced by many factors, including
      microcatheter type, steaming, shaping, sterilization, and manual handling.

PMID- 12223366
TI  - Intraarterially administered verapamil as adjunct therapy for cerebral vasospasm:
      safety and 2-year experience.
AB  - BACKGROUND AND PURPOSE: Despite the widespread use of angioplasty, adjunct
      chemical therapy is often needed to treat patients with cerebral vasospasm. In
      this study, we examined the safety of intraarterial administration of verapamil
      to patients with cerebral vasospasm. We herein summarize our 2-year experience
      with this treatment. METHODS: We retrospectively reviewed the procedure reports,
      anesthesia records, clinical charts, and brain images of 29 patients who received
      intraarterially administered verapamil in 34 procedures for the treatment of
      vasospasm after subarachnoid hemorrhage from July 1998 to June 2000. The average
      changes in mean arterial pressure and heart rate were used to measure
      cardiovascular side effects. The neurologic effects were assessed by angiographic
      findings, the results of neurologic examinations performed before and after the
      procedure, and findings of CT of the head. RESULTS: The average dose of verapamil
      per patient was 3 +/- 0 mg or 44 +/- 5 mcg/kg. The average changes in mean
      arterial pressure at 10 and 20 minutes were -5 +/- 1 mm Hg and -2 +/- 1 mm Hg or 
      3.8 +/- 1.0% and -1.7 +/- 1.1%, respectively. No significant change of heart rate
      was observed at 10 minutes. The patients showed no sign of increased intracranial
      pressure by hemodynamic parameters, neurologic examination, or CT of the head. On
      10 occasions, when the effect of verapamil infusion was assessed
      angiographically, there was 44 +/- 9% increase of vessel diameter in the spastic
      segment. Neurologic improvement was noted after five of 17 procedures when
      verapamil was used as the sole treatment. CONCLUSION: Low dose verapamil is safe
      when administered intraarterially to patients with cerebral vasospasm. Beneficial
      effects are achieved in some patients, prompting further study of its efficacy.

PMID- 12223367
TI  - Saccular aneurysm associated with posterior cerebral artery fenestration
      manifesting as a subarachnoid hemorrhage in a child.
AB  - Fenestrations of the cerebral arteries are uncommon, and aneurysms in association
      with fenestrations are even more uncommon. We report the case of a saccular
      aneurysm associated with a posterior cerebral artery fenestration in a child with
      subarachnoid hemorrhage. The patient was successfully treated with Guglielmi
      detachable coils. This case is unusual because of the patient's age and the
      location of the fenestration.

PMID- 12223368
TI  - Transdural blood supply to cerebral arteriovenous malformations adjacent to the
      dura mater.
AB  - BACKGROUND AND PURPOSE: Subpial cerebral arteriovenous malformations (AVMs) can
      develop a transdural arterial blood supply. The relationships between AVM volume,
      patient age, embolization and prior hemorrhage, and the frequency of transdural
      blood supply were investigated. METHODS: During 1997-1999, 105 consecutive
      patients with 107 AVMs adjacent to the dura mater were treated with embolization
      at one center. One of the authors, who was not directly involved in the
      treatment, retrospectively reviewed the angiograms. Patient histories were
      collected from hospital records. RESULTS: Angiograms obtained before the first
      embolization included a selective injection into the dural arteries in 86 (80%)
      AVMs. Thirty-six (42%) of those had transdural blood supply. The frequency
      increased with AVM volume and patient age but not with intracranial hemorrhage.
      Follow-up angiograms obtained subsequent to at least one embolization were
      available in 32 patients who had no transdural blood supply at the first
      examination. In eight (25%) patients, a transdural blood supply developed during
      a mean treatment time of 12 months. CONCLUSION: A transdural blood supply is
      common in AVMs adjacent to the dura mater. The frequency increases with AVM
      volume and patient age. Intracranial hemorrhage does not seem to be a
      predisposing event. Transarterial embolization appears to induce factors that
      promote the development of a transdural blood supply.

PMID- 12223369
TI  - Prognosis of central retinal artery occlusion: local intraarterial fibrinolysis
      versus conservative treatment.
AB  - BACKGROUND AND PURPOSE: Local intraarterial fibrinolysis (LIF) is one of several
      methods used in treating central retinal artery occlusion (CRAO). We investigated
      whether LIF is more effective than conservative methods in the treatment of CRAO.
      METHODS: In this retrospective study, a total of 178 patients (125 men and 53
      women) with CRAO were treated at the Eye Hospital of the University of Freiburg
      from 1980 to 2000. The average age of the patients was 66.8 years (SD, 12 years).
      In group I, 116 patients were treated conservatively by anterior chamber
      paracentesis, massage of the globe, isovolemic hemodilution, acetazolamide,
      Pentoxifyllin, acetylsalicylic acid, and reduction of arterial hypertension. Some
      combination but not all of the mentioned conservative methods were used in the
      conservatively treated patients. In group II, 62 patients receiving LIF received
      local injection of urokinase or recombinant tissue plasminogen activator into the
      proximal part of the ophthalmic artery. In case of ipsilateral carotid artery
      occlusion or high grade stenosis (14 of 62 patients), the thrombolytic agent was
      administered into the internal maxillary artery. RESULTS: Among 178 patients, the
      CRAO was subtotal in 130 (73.0%), incomplete in 39 (21.9%), and total in nine
      (5.1%). Statistical calculations showed a significantly better visual acuity in
      group II patients, who were treated with LIF, in comparison with group I
      patients, who were treated conservatively (P =.0022). CONCLUSION: For patients
      with CRAO, LIF is superior to conservative treatment.

PMID- 12223370
TI  - Intracranial balloon angioplasty of acute terminal internal carotid artery
      occlusions.
AB  - Acute embolic occlusion of the intracranial internal carotid bifurcation is
      associated with a poor prognosis. Recanalization rates of this lesion with
      intravenous or intraarterial thrombolysis are exceedingly low. We describe the
      use of balloon angioplasty after failed thrombolysis to achieve immediate
      recanalization of acute carotid T occlusions in two patients. At 1-month follow
      up, both patients were alive with neurologic deficits. For acute carotid T
      occlusion, balloon angioplasty should be considered a first-line endovascular
      therapy.

PMID- 12223371
TI  - Cytoarchitecture of the human cerebral cortex: MR microscopy of excised specimens
      at 9.4 Tesla.
AB  - BACKGROUND AND PURPOSE: The laminar patterns displayed by MR microscopy (MRM)
      form one basis for the classification of the cytoarchitectonic areas (Brodmann
      areas). It is plausible that in the future MRM may depict Brodmann areas
      directly, and not only by inference from gross anatomic location. Our purpose was
      to depict the laminar cytoarchitecture of excised, formalin-fixed specimens of
      human cerebral cortex by use of 9.4-T MR and to correlate MR images with
      histologic stains of the same sections. METHODS: Formalin-fixed samples of human
      sensory isocortex (calcarine, Heschl's, and somatosensory cortices), motor
      isocortex (hand motor area of M1), polar isocortex (frontal pole), allocortex
      (hippocampal formation), and transitional periallocortex (retrosplenial cortex)
      were studied by MRM at 9.4 T with intermediate-weighted pulse sequences for a
      total overnight acquisition time of 14 hours 17 minutes for each specimen. The
      same samples were then histologically analyzed to confirm the MR identification
      of the cortical layers. Curves representing the change in MR signal intensity
      across the cortex were generated to display the signal intensity profiles for
      each type of cortex. RESULTS: High-field-strength MR imaging at a spatial
      resolution of 78 x 78 x 500 micro m resolves the horizontal lamination of
      isocortex, allocortex, and periallocortex and displays specific intracortical
      structures such as the external band of Baillarger. The signal intensity profiles
      demonstrate the greatest hypointensity at the sites of maximum myelin
      concentration and maximum cell density and show gradations of signal intensity
      inversely proportional to varying cell density. CONCLUSION: MRM at 9.4 T depicts
      important aspects of the cytoarchitecture of normal formalin-fixed human cortex.

PMID- 12223372
TI  - Human brain hemorrhage: quantification of perihematoma edema by use of diffusion
      weighted MR imaging.
AB  - BACKGROUND AND PURPOSE: Animal models have clearly shown a critical role for
      extravascular blood in the initiation of the vasogenic edema associated with
      intracerebral hemorrhage (ICH). Nevertheless, the relevance of these observations
      to the human disease process has not been evaluated. With a prospectively
      collected cohort of nine patients, we report the relation between
      intraparenchymal blood clot volume and elevation of perihematoma brain tissue
      (and homologous contralateral brain tissue) apparent diffusion coefficient (ADC).
      METHODS: Patients with acute and subacute supratentorial ICH were prospectively
      evaluated by using diffusion-weighted imaging. ADC was measured in perihematoma
      tissue and in homologous contralateral regions. The relationship between ADC and
      volume of hematoma was determined by using linear regression analysis. RESULTS:
      Nine patients were enrolled in the study. The mean hematoma volume was 30.8 cc
      (range, 2.6-74 cc). The ADC in the perihematoma regions was 172.5 x 10(-5)
      mm(2)/s (range, 120.1-302.5 x 10(-5) mm(2)/s) and in the contralateral
      corresponding regions of interest was 87.6 x 10(-5) mm(2)/s (range, 76.5-102.1 x
      10(-5) mm(2)/s) (P=.02). The Pearson correlation coefficient for the ADC in
      surrounding edema and hematoma volume was 0.7 (P=.04). The correlation
      coefficient between hematoma volume and contralateral hemisphere ADC was 0.8
      (P=.02). CONCLUSION: We report a significant direct correlation between ICH
      volume and degree of ADC elevation in perihematoma and ADC values in
      contralateral corresponding brain tissue. These findings suggest a dose-effect
      interaction between volume and concentration of blood products and intensity of
      response that brain tissue exhibits in blood-mediated edema. Prospective natural
      history and interventional studies are required to confirm this biologically
      meaningful correlation in patients with ICH.

PMID- 12223373
TI  - Age-related total gray matter and white matter changes in normal adult brain.
      Part I: volumetric MR imaging analysis.
AB  - BACKGROUND AND PURPOSE: A technique of segmenting total gray matter (GM) and
      total white matter (WM) in human brain is now available. We investigated the
      effects of age and sex on total fractional GM (%GM) and total fractional WM (%WM)
      volumes by using volumetric MR imaging in healthy adults. METHODS: Fifty-four
      healthy volunteers (22 men, 32 women) aged 20-86 years underwent dual-echo fast
      spin-echo MR imaging. Total GM, total WM, and intracranial space volumes were
      segmented by using MR image-based computerized semiautomated software. Volumes
      were normalized as a percentage of intracranial volume (%GM and %WM) to adjust
      for variations in head size. Age and sex effects were then assessed. RESULTS:
      Both %GM and %WM in the intracranial space were significantly less in older
      subjects (> or =50 years) than in younger subjects (<50 years) (P <.0001 and P
      =.02, respectively). Consistently, %GM decreased linearly with age, beginning in
      the youngest subjects. %WM decreased in a quadratic fashion, with a greater rate
      beginning only in adult midlife. Although larger GM volumes were observed in men
      before adjustments for cranium size, no significant differences in %GM or %WM
      were observed between the sexes. CONCLUSION: GM volume loss appears to be a
      constant, linear function of age throughout adult life, whereas WM volume loss
      seems to be delayed until middle adult life. Both appear to be independent of
      sex. Quantitative analysis of %GM and %WM volumes can improve our understanding
      of brain atrophy due to normal aging; this knowledge may be valuable in
      distinguishing atrophy of disease patterns from characteristics of the normal
      aging process.

PMID- 12223374
TI  - Age-related total gray matter and white matter changes in normal adult brain.
      Part II: quantitative magnetization transfer ratio histogram analysis.
AB  - BACKGROUND AND PURPOSE: The magnetization transfer ratio (MTR) is a sensitive and
      quantitative identifier of underlying structural changes in the brain. We
      quantitatively evaluated age- and sex-related MTR changes in global gray matter
      (GM) and global white matter (WM) in healthy adults. METHODS: Fifty-two healthy
      volunteers (21 men, 31 women) aged 20-86 years underwent dual-echo fast spin-echo
      and magnetization transfer imaging performed with and then without a saturation
      pulse. GM and WM were distinguished by using a computer-assisted semiautomated
      segmentation technique. MTR histograms were generated for each segmented tissue
      in each subject and compared among age and sex groups. RESULTS: The mean, median,
      first quartile, and peak height of the MTR histogram were significantly lower in
      the older group (> or =50 years) than those in the younger group (<50 years) for
      both GM and WM. The age dependency of these values can be expressed in a
      quadratic fashion over the entire span of adulthood. The MTRs started to decline
      only after the age of approximately 40 years in both tissues. No statistically
      significant differences in MTR histogram measurements between the sexes were
      observed. CONCLUSION: The different MTR values for both GM and WM in the two age
      groups suggest that notable microscopic changes occur in GM and WM with advancing
      age, yet no significant sex-related variations in MTR measurements were found in
      these neurologically healthy adults. Such normative data based on the inherent
      contrast in MTRs are essential in studies of specific disorders of aging, and
      they may have implications for our understanding of the gross structural changes
      in both GM and WM in the aging brain.

PMID- 12223375
TI  - Hemodynamic modifications in patients with symptomatic unilateral stenosis of the
      internal carotid artery: evaluation with MR imaging perfusion sequences.
AB  - BACKGROUND AND PURPOSE: Risk of developing ischemia is higher in patients with
      reduced cerebrovascular reactivity than in those with preserved cerebrovascular
      reactivity. Therefore, we assessed cerebral hemodynamic modifications in patients
      with unilateral stenosis of the internal carotid artery by using perfusion
      weighted MR imaging to determine if these modifications underlie or anticipate
      ischemic signs and symptoms. METHODS: Fifteen patients with unilateral 70-90%
      carotid artery stenosis were studied with digital subtraction angiography and
      perfusion-weighted MR imaging. Their findings were compared with those of 15 age-
      and sex-matched control subjects. Regional cerebral blood volume (rCBV) and mean
      transit time (MTT) values were calculated in the middle cerebral artery and
      border zone territories. RESULTS: No significant difference was noted in rCBV and
      MTT values between the hemispheres in the symptomatic patients. There was a
      significant difference in MTT values in the border zones between patients and
      control subjects. MR images in patients and control subjects did not reveal large
      territorial infarcts and did reveal similar white matter lesion burdens.
      CONCLUSION: There is adequate compensation of unilateral stenosis when the
      stenosis is less than 90%. The risk of stroke is higher in patients with stenoses
      exceeding 70%, mostly because of decreased collateral reserve when confronted
      with emboli.

PMID- 12223376
TI  - Contrast-enhanced 2D cine phase MR angiography for measurement of basilar artery
      blood flow in posterior circulation ischemia.
AB  - BACKGROUND AND PURPOSE: Dizziness is a symptom that develops with internal ear
      disturbances and with dysfunctions of the brain stem and cerebellum, in
      particular with blood flow disturbances of the brain stem and cerebellum
      (posterior circulation ischemia [PCI]). Patients with PCI often present with
      various neurologic signs and symptoms. To examine the usefulness of contrast
      enhanced 2D cine phase MR angiography in the diagnosis of PCI, we examined
      quantitative blood flow of the basilar artery in patients with PCI who had
      primarily complained of dizziness. METHODS: We quantitatively measured the blood
      flow volume rate of the basilar artery by using a contrast-enhanced 2D cine phase
      MR angiographic technique in 21 patients diagnosed with PCI and in 16 age- and
      sex-matched control participants. RESULTS: Maximum and mean average flow
      velocities of the basilar artery in the PCI group were significantly lower than
      those of the control group (29.2 +/- 9.2 cm/s versus 38.5 +/- 8.2 cm/s [P <.005]
      and 18.0 +/- 5.6 cm/s versus 22.6 +/- 5.0 cm/s [P <.01], respectively). The flow
      volume rates of the basilar arteries were also significantly lower in the PCI
      group (103.3 +/- 37.3 mL/min versus 148.8 +/- 40.0 mL/min [P <.001]). CONCLUSION:
      The flow volume rate of the basilar artery in patients with PCI during
      intermittent ischemic attacks with dizziness was chronically reduced compared
      with that in the control participants. This suggests that flow volume rates may
      influence the development of the clinical signs and symptoms of PCI. We think
      that contrast-enhanced 2D cine phase MR angiography is a valuable method for the
      diagnosis of PCI.

PMID- 12223377
TI  - Transcranial doppler sonography and CT angiography in patients with
      atherothrombotic middle cerebral artery stroke.
AB  - BACKGROUND AND PURPOSE: Atherothrombotic disease of the middle cerebral artery
      (MCA) frequently occurs in Asian populations. This abnormality can be
      noninvasively assessed with transcranial Doppler sonography (TCD) and computed
      tomographic angiography (CTA). To our knowledge, the usefulness of TCD sonography
      compared with CTA in the diagnosis of nonembolic MCA disease has not been
      studied. METHODS: We prospectively examined 70 patients with clinically suspected
      atherothrom botic MCA stroke by using TCD sonography and CTA. We excluded
      patients with a known source of cardiac emboli, significant carotid stenosis, or
      classic lacunar syndrome. TCD sonography was performed within 2 days of
      admission, followed by CTA within 7 days after stroke onset. RESULTS: CTA
      demonstrated MCA stenosis of more than 50% in 57 patients (81%), whereas only 29
      patients (41%) had abnormal TCD findings. CTA showed proximal M1 stenosis, distal
      M1 stenosis, and M2 disease in 29%, 29%, and 24% of the patients, respectively.
      Stenotic sites differed between patients with normal TCD results and those with
      abnormal results. TCD findings correlated well with CTA findings in all patients
      with proximal M1 stenosis. In contrast, TCD sonography correctly depicted distal
      M1 or M2 disease in only 24% of the patients. CONCLUSION: In this population, CTA
      is superior to TCD sonography in the diagnosis of MCA disease. Abnormal TCD
      results are highly suggestive of MCA stenosis. However, normal TCD findings do
      not exclude such lesions, especially in patients with distal M1 or M2 disease.
      Because distal M1 and M2 disease was found in half of our patients, TCD
      sonography should not be used as a method to screen for MCA stenosis.

PMID- 12223378
TI  - Prominent matched hypoperfusion in an intact cerebellum after a solitary middle
      cerebellar peduncle infarct.
AB  - We examined the cerebellar metabolism of a 61-year-old man with a small infarct
      in the left middle cerebellar peduncle and an intact cerebellum. Positron
      emission tomographic images obtained 28 days after onset showed prominent
      hypoperfusion and hypometabolism (almost 50% below the normal level) in the left
      cerebellar hemisphere. This case report shows that neural deafferentation may
      cause prominent hypometabolism without morphologic changes in the cerebellum. An
      arrest in synaptic activity may be the most important factor for the adaptive
      decrease in oxygen metabolism seen in ischemic brain.

PMID- 12223379
TI  - Multisection proton MR spectroscopy for mesial temporal lobe epilepsy.
AB  - BACKGROUND AND PURPOSE: Extensive metabolic impairments have been reported in
      association with mesial temporal lobe epilepsy (mTLE). We investigated whether
      proton MR spectroscopy ((1)H-MRS) depicts metabolic changes beyond the
      hippocampus in cases of mTLE and whether these changes help lateralize the
      seizure focus. METHODS: MR imaging and (1)H-MRS were performed in 15 patients
      with mTLE with a postoperative diagnosis of mesial temporal sclerosis and in 12
      control volunteers. Point-resolved spectroscopy and multisection (1)H-MRS
      measured N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) in the
      hippocampus, temporal opercular and lateral cortices, insula and cerebellum, and
      frontal, parietal, and occipital lobes. Metabolites were assessed as ratios to Cr
      and in absolute units. RESULTS: Twelve patients had ipsilateral hippocampal
      atrophy; three had negative imaging results. In the ipsilateral hippocampus,
      absolute NAA (/NAA/) was 27.3% lower in patients compared with that in control
      volunteers (P <.001) and 18.5% lower compared with that in the contralateral side
      (P <.01). /NAA/ averaged over selected regions in the ipsilateral temporal lobes
      of patients with mTLE was 19.3% lower compared with the mean in the control group
      (P <.0001) and by 17.7% lower compared with the contralateral values (P <.00001).
      Using only hippocampal data, 60% of the cases of mTLE were correctly lateralized.
      Lateralization, determined using whole temporal lobe data, had 87% sensitivity
      and 92% specificity. /NAA/ was bilaterally reduced in the frontal, parietal, and
      occipital lobes of patients with mTLE compared with that in control volunteers (P
      <.01). CONCLUSION: Multisection (1)H-MRS depicts interictal reductions of NAA in
      the ipsilateral temporal lobe beyond the hippocampus and accurately lateralizes
      seizure foci.

PMID- 12223380
TI  - Brain abscess and necrotic brain tumor: discrimination with proton MR
      spectroscopy and diffusion-weighted imaging.
AB  - BACKGROUND AND PURPOSE: Discriminating pyogenic brain abscesses from cystic or
      necrotic tumors is sometimes difficult with CT or MR imaging. We compared
      findings of proton MR spectroscopy ((1)H-MRS) with those of diffusion-weighted
      imaging to determine which technique was more effective for this differential
      diagnosis. METHODS: Fourteen patients (necrotic or cystic tumor [n = 7]; pyogenic
      abscess [n = 7]) who underwent 1.5-T (1)H-MRS and diffusion-weighted imaging and
      had findings of ring-shaped enhancement after contrast agent administration were
      enrolled in this study. Diffusion-weighted imaging was performed with a single
      shot spin-echo echo-planar pulse sequence (b = 1000 s/mm(2)). The apparent
      diffusion coefficient and ratio were also measured. RESULTS: Spectra for two
      patients were unacceptable because of either poor shimming conditions or
      contamination from neighboring fat. Spectra in three of five patients with
      abscess had lactate, amino acids (including valine, alanine, and leucine), and
      acetate peaks; one of the three spectra had an additional peak of succinate. In
      one patient with abscess treated by antibiotics, only lactate and lipid peaks
      were detected. Spectra for four of seven patients with cystic or necrotic tumors
      showed only lactate peaks. Lactate and lipids were found in three patients with
      tumors. Hyperintensity was seen in all the pyogenic abscess cavities and
      hypointensity in all the cystic and necrotic tumors on diffusion-weighted images.
      CONCLUSION: (1)H-MRS and diffusion-weighted imaging are useful for
      differentiating brain abscess from brain tumor, but the latter requires less time
      and is more accurate than is (1)H-MRS. (1)H-MRS is probably more limited in cases
      of smaller peripheral lesions, skull base lesions, and treated abscesses.

PMID- 12223381
TI  - Proton MR spectroscopy of tumefactive demyelinating lesions.
AB  - BACKGROUND AND PURPOSE: Tumefactive demyelinating lesions (TDLs) can simulate
      intracranial neoplasms in clinical presentation and MR imaging appearance, and
      surgical biopsy is often performed in suspected tumors. Proton MR spectroscopy
      has been applied in assessing various intracranial diseases and is increasingly
      used in diagnosis and clinical management. Our purpose was to determine if
      multivoxel proton MR spectroscopy can be used to differentiate TDLs and high
      grade gliomas. METHODS: Conventional MR images, proton MR spectra, and medical
      records were retrospectively reviewed in six patients with TDLs diagnosed by
      means of biopsy or by documented clinical improvement, with or without supporting
      laboratory testing and follow-up imaging. Proton MR spectra of 10 high-grade
      gliomas with similar conventional MR imaging appearances were used for
      comparison. In contrast-enhancing, central, and perilesional areas of each
      lesion, peak heights of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr)
      were measured and the lactate peak noted. Cho/Cr and NAA/Cr ratios of
      corresponding regions in TDLs and gliomas were compared. RESULTS: No significant
      differences in mean Cho/Cr ratios were found in the corresponding contrast
      enhancing, central, or perilesional areas of TDLs and gliomas. The mean central
      region NAA/Cr ratio in gliomas was significantly lower than that of TDLs, but
      mean NAA/Cr ratios in other regions were not significantly different. A lactate
      peak was identified in four of six TDLs and three of 10 gliomas. CONCLUSION: In
      the cases examined, the NAA/Cr ratio in the central region of TDLs and high-grade
      gliomas differed significantly. However, overall metabolite profiles of both
      lesions were similar; this finding emphasizes the need for the cautious
      interpretation of spectroscopic findings.

PMID- 12223382
TI  - Proton chemical shift imaging in pick complex.
AB  - BACKGROUND AND PURPOSE: Pick complex (PC) is the name given to a group of
      diseases comprising Pick disease and its variations, all of which have a large
      degree of pathologic and clinical overlap. Because of this overlap, the
      observation of neuropathologic changes in vivo is difficult, although these
      changes play important roles in the criteria used for classification. The purpose
      of this study was to evaluate changes in brain metabolism in PC with proton
      chemical shift imaging ((1)H-CSI). METHODS: Nine patients with PC (three each
      with frontotemporal dementia, corticobasal degeneration [CBD], and primary
      progressive aphasia [PPA]) and five healthy subjects underwent (1)H-CSI. Volumes
      of interest were selected at the level of the basal ganglia by using a spin-echo
      sequence (TR/TE, 2000/13). Peak areas and ratios of N-acetylaspartate (NAA),
      creatine (Cr), and choline (Cho) were calculated in voxels in the basal ganglia
      and perisylvian regions. RESULTS: Reduced NAA/Cho ratios were observed in the
      right basal ganglia of the patients with PC. In patients with CBD or PPA, low
      NAA/Cr values were detected in the right perisylvian region. CONCLUSION: In PC,
      (1)H-CSI decreased NAA values in a wide area. Significantly reduced NAA levels in
      the right hemisphere in patients with PC suggests a neurodegenerative change and
      may reflect cases in which the right hemisphere is dominantly affected, compared
      with the left hemisphere. (1)H-CSI provided information that could not be
      obtained with other imaging techniques. Thus, (1)H-CSI may provide useful
      information for understanding the pathologic process underlying PC.

PMID- 12223383
TI  - Integrating postprocessed functional MR images with picture archiving and
      communication systems.
AB  - We describe a method of converting postprocessed functional MR images to the
      Digital Imaging and Communications in Medicine (DICOM) standard and sending these
      DICOM images directly into any picture archiving and communication system (PACS)
      or stand-alone DICOM database. This method provides system-wide access and
      archiving of previously research-only applications, it permits the clinical
      review of postprocessed data on DICOM-compliant workstations, and it can be used
      to move functional MR data onto intraoperative neuronavigational workstations for
      surgical guidance. The procedure can be used with any MR postprocessed dataset,
      and it can be extended to other imaging modalities.

PMID- 12223384
TI  - MR changes after acute cyanide intoxication.
AB  - We describe MR changes that occurred 3 and 6 weeks after a suicide attempt with
      cyanide. The toxicity of cyanide causes damage, primarily to the basal ganglia,
      and those changes were visible as altered signal intensity on the first MR
      images. Extensive areas of hemorrhagic necrosis were seen 6 weeks later. Our case
      shows pseudolaminar necrosis along the central cerebral cortex 3 weeks after
      cyanide poisoning, showing that the sensorimotor cortex is also a site for toxic
      necrosis because of its high oxygen dependency.

PMID- 12223385
TI  - Polycythemia mimicking venous sinus thrombosis.
AB  - Venous sinus thrombosis is a relatively uncommon disorder that frequently is
      associated with confusing clinical findings and delayed diagnosis. Patients are
      often screened with unenhanced CT, and CT findings may be subtle and may include
      hyperattenuation of cerebral veins or venous sinuses secondary to intracranial
      thrombosis. This hyperattenuation may be mimicked by polycythemia, as shown in
      this case.

PMID- 12223386
TI  - Increased uptake of technetium-99m-hexamethylpropyleneamine oxime related to
      primary leptomeningeal melanoma.
AB  - We present an autopsy case of primary leptomeningeal melanoma visualized with
      technetium-99m-hexamethylpropyleneamine oxime (Tc-99m-HMPAO) single photon
      emission CT (SPECT) of the brain. Increased uptake of Tc-99m-HMPAO coincided with
      leptomeningeal enhancement on MR images and with the tumor location of the
      autopsy findings. It was thought that Tc-99m-HMPAO could correlate closely with
      melanoma. Tc-99m-HMPAO SPECT clearly showed primary leptomeningeal melanoma and
      severe hypoperfusion induced by intracranial hypertension and tumor
      proliferation.

PMID- 12223387
TI  - High-spatial-resolution MR cisternography of the cerebellopontine angle in 90
      seconds with a zero-fill interpolated fast recovery 3D fast asymmetric spin-echo
      sequence.
AB  - BACKGROUND AND PURPOSE: Although the 12-minute 3D fast asymmetric spin-echo
      (FASE) protocol for imaging the inner ear has been satisfactory, reducing imaging
      time to minimize patient discomfort and maximize system throughput is desirable.
      We therefore evaluated the performance of a zero-fill interpolated (ZIP) fast
      recovery 3D FASE sequence in screening for cerebellopontine (CP) angle lesions in
      90 seconds. METHODS: Thirty consecutive patients known or suspected to have CP
      angle lesions underwent MR imaging at 1.5 T with use of bilateral quadrature
      phased-array coils designed for examination of the CP angle. Conventional 3D FASE
      images (4000/240/1 [TR/TE/NEX]) were obtained in 11 minutes 48 seconds with a
      field of view (FOV) of 16 cm, matrix of 512 x 512 x 40, section thickness of 0.8
      mm, and echo train length of 80. Then, ZIP fast recovery 3D FASE images
      (2000/240/1) were obtained in 90 seconds by using the same FOV. Contrast-enhanced
      T1-weighted 3D spoiled gradient-echo (SPGR) images were obtained as the reference
      standard. Three radiologists evaluated the images independently. Conventional 3D
      FASE and ZIP fast recovery 3D FASE images were reviewed at separate sessions.
      RESULTS: On 3D SPGR images, 10 tumors were detected in 10 of the 30 patients. All
      lesions were depicted with both 3D FASE protocols. There were no false-positive
      results with either 3D FASE protocol. Both protocols showed 100% sensitivity and
      100% specificity for all three reviewers. CONCLUSION: High-spatial-resolution MR
      cisternography with the ZIP fast recovery 3D FASE protocol in 90 seconds results
      in a substantial reduction (by a factor of about eight) in the time required for
      screening for CP angle lesions compared with the previously reported conventional
      3D FASE protocol, while maintaining high sensitivity and specificity.

PMID- 12223388
TI  - CT and MR imaging characteristics of intravestibular lipoma.
AB  - BACKGROUND AND PURPOSE: Intracranial lipomas are uncommon congenital
      malformations that most often are asymptomatic. A rare subset of intracranial
      lipomas arises within the vestibule of the inner ear, which can cause
      sensorineural hearing loss. We present the CT and MR imaging characteristics of
      lipomas within the vestibule of the inner ear and propose a pathogenetic
      mechanism for this malformation. METHODS: We retrospectively reviewed five cases
      of vestibular lipoma. T1-weighted axial conventional spin-echo and T2-weighted
      axial fast spin-echo sequences were performed in all five cases. Four patients
      underwent T1-weighted fat-saturated imaging, and one underwent CT scanning with
      Hounsfield units measured. RESULTS: Four female patients ranging in age from 10
      to 40 years and one 26-year-old male patient had sensorineural hearing loss. Two
      patients had progressive high-frequency loss; one, sudden-onset high-frequency
      loss; and two, congenital high-frequency loss. All had lesions within the
      vestibule that displayed hyperintensity on T1-weighted images, isointensity to
      slight hypointensity on T2-weighted fast spin-echo images, hypointensity with fat
      saturation, and fat attenuation on CT scans. Three of the cases were associated
      with lipoma of the cerebellopontine angle. In none of these cases were the
      cerebellopontine angle and labyrinthine lipomas contiguous. CONCLUSION:
      Intravestibular lipoma is considered when a focal hyperintense lesion is
      identified within the vestibule of the inner ear on T1-weighted MR images. Lesion
      hypointensity on fat-saturated T1-weighted MR images verifies its lipomatous
      nature and separates it from intralabyrinthine hemorrhage or highly proteinaceous
      fluid.

PMID- 12223389
TI  - Ultrasonographic evaluation of vertebral venous valves.
AB  - To date, vertebral venous valves have not been studied clinically or by
      sonography. This report reveals that these valves could be studied noninvasively
      by using sonographic techniques. Real-time sonography clearly showed the opening
      and closing of the two cusps of vertebral venous valves at the junction of the
      vertebral vein and the brachiocephalic vein, which move synchronously with the
      internal jugular venous valves. This is the first time the vertebral venous
      valves have been studied by using clinical sonography. This might provide a new
      point of view for evaluating the clinical significance of vertebral venous
      valves.

PMID- 12223390
TI  - MR spectroscopic findings in a case of Alpers-Huttenlocher syndrome.
AB  - Alpers-Huttenlocher syndrome, considered a mitochondrial disease, combines
      encephalopathy and liver failure. An 11-year-old boy with Alpers-Huttenlocher
      syndrome underwent conventional MR imaging, diffusion-weighted imaging, and
      proton MR spectroscopy. Diffusion-weighted imaging showed cytotoxic edema
      interpreted as acute-phase encephalopathy. MR spectroscopy revealed a lactate
      peak in the cortex that appeared abnormal on diffusion-weighted images, possibly
      representing respiratory deficiency with anaerobic metabolism. MR spectroscopy
      proved to be more sensitive regarding lactate detection than did neurometabolic
      examination of serum and CSF. A reduced N-acetylaspartate-creatine ratio was
      detected in both the cortex that appeared abnormal and the cortex that appeared
      normal on the diffusion-weighted images, indicating neuronal damage that was
      widespread, even beyond the boundaries of conventional MR imaging changes.

PMID- 12223391
TI  - Metachromatic leukodystrophy: diffusion MR imaging findings.
AB  - Herein the case of a 10-month-old boy with metachromatic leukodystrophy is
      reported. Diffusion MR imaging performed with an echo-planar trace sequence
      revealed a cytotoxic edema-like pattern (high signal intensity on b = 1000
      s/mm(2) images and low apparent diffusion coefficient values) in the affected
      white matter in the absence of an ischemic condition. This finding was unchanged
      at a 6-month follow-up, as revealed by diffusion MR imaging. A gradient-echo
      diffusion sequence, reverse fast imaging in steady-state precession, revealed
      hyperintense changes at the corresponding regions. It is likely that the
      cytotoxic edematous pattern (restricted diffusion pattern) reflected restriction
      of mobility of the water molecules within abnormal portions of the myelin sheath,
      because impaired myelin breakdown and reutilization are known features of
      metachromatic leukodystrophy.

PMID- 12223392
TI  - Sequential MR imaging of denervated muscle: experimental study.
AB  - BACKGROUND AND PURPOSE: MR changes in denervated muscles have been reported to
      occur within days up to several weeks after peripheral nerve damage. The purpose
      of this experimental study was to investigate the longitudinal changes in
      denervated muscles by using MR imaging. METHODS: In 12 Lewis rats, the left
      sciatic nerve was transected at the level of the proximal thigh. MR imaging of
      both legs was performed before and 1 hour, 24 hours, 48 hours, 7 days, 14 days,
      28 days, and 2 months after the procedure. The MR protocol included T1-weighted
      spin-echo, T2-weighted double turbo spin-echo, and turbo inversion recovery
      magnitude (TIRM) sequences obtained in the axial plane. Signal intensities (T2
      weighted double turbo spin-echo and TIRM sequences) and the T2 TR (T2-weighted
      double turbo spin-echo sequence) were recorded for the soleus, peroneal, and
      gracilis muscles of both sides. Moreover, the circumferences of both lower legs
      were determined on the basis of T1-weighted images. RESULTS: Twenty-four hours
      after denervation, a signal intensity increase in the denervated peroneal and
      soleus muscles was present on TIRM images. On T2-weighted images, only the
      peroneal muscle exhibited slightly increased signal intensities and T2 TR. Forty
      eight hours after nerve transection, the denervated soleus and peroneal muscles
      revealed prolonged T2 TR and marked increased signal intensities on T2-weighted
      and TIRM images when compared with the contralateral side, which further
      increased at or less than 2 months after denervation. Muscle atrophy of the
      denervated muscles was present as early as 7 days after denervation and was also
      increased at follow-up examinations. CONCLUSION: The TIRM sequence is more
      sensitive than is T2-weighted imaging in the detection of signal intensity
      changes in denervated muscle. These changes occur as early as 24 (TIRM sequence)
      and 48 (T2-weighted sequence) hours, respectively, after complete transection of
      the sciatic nerve in rats and precede muscle atrophy. The sensitivity to early
      signal intensity changes in denervated muscles may support the use of MR imaging
      in the diagnosis of peripheral nerve lesions.

PMID- 12223395
TI  - Delayed stroke secondary to increasing mass effect after endovascular treatment
      of a giant aneurysm by parent vessel occlusion.

PMID- 12223396
TI  - Radiculomyelitic rabies.

PMID- 12223397
TI  - Developmental functions of the Distal-less/Dlx homeobox genes.
AB  - Distal-less is the earliest known gene specifically expressed in developing
      insect limbs; its expression is maintained throughout limb development. The
      homeodomain transcription factor encoded by Distal-less is required for the
      elaboration of proximodistal pattern elements in Drosophila limbs and can
      initiate proximodistal axis formation when expressed ectopically. Distal-less
      homologs, the Dlx genes, are expressed in developing appendages in at least six
      phyla, including chordates, consistent with requirements for Dlx function in
      normal appendage development across the animal kingdom. Recent work implicates
      the Dlx genes of vertebrates in a variety of other developmental processes
      ranging from neurogenesis to hematopoiesis. We review what is known about the
      invertebrate and vertebrate Dll/Dlx genes and their varied roles during
      development. We propose revising the vertebrate nomenclature to reflect
      phylogenetic relationships among the Dlx genes.

PMID- 12223398
TI  - Cement gland-specific activation of the Xag1 promoter is regulated by co
      operation of putative Ets and ATF/CREB transcription factors.
AB  - The cement gland marks the extreme anterior ectoderm of the Xenopus embryo, and
      is determined through the overlap of several positional domains. In order to
      understand how these positional cues activate cement gland differentiation, the
      promoter of Xag1, a marker of cement gland differentiation, was analyzed.
      Previous studies have shown that Xag1 expression can be activated by the anterior
      specific transcription factor Otx2, but that this activation is indirect. 102 bp
      of upstream genomic Xag1 sequence restricts reporter gene expression specifically
      to the cement gland. Within this region, putative binding sites for Ets and
      ATF/CREB transcription factors are both necessary and sufficient to drive cement
      gland-specific expression, and cooperate to do so. Furthermore, while the
      putative ATF/CREB factor is activated by Otx2, a factor acting through the
      putative Ets-binding site is not. These results suggest that Ets-like and
      ATF/CREB-like family members play a role in regulating Xag1 expression in the
      cement gland, through integration of Otx2 dependent and independent pathways.

PMID- 12223399
TI  - COP9 signalosome subunits 4 and 5 regulate multiple pleiotropic pathways in
      Drosophila melanogaster.
AB  - The COP9 signalosome (CSN) is an essential eight-subunit repressor of light
      regulated development in Arabidopsis. This complex has also been identified in
      animals, though its developmental role remains obscure. CSN subunits have been
      implicated in various cellular processes, suggesting a possible role for the CSN
      as an integrator of multiple signaling pathways. In order to elucidate the
      function of the CSN in animals, a Drosophila model system has previously been
      established. Gel-filtration analysis with antibodies against CSN subunits 4, 5
      and 7 revealed that these proteins act as a complex in Drosophila that is similar
      in size to the plant and mammalian complexes. Null mutations in either one of two
      subunits, CSN4 or CSN5, are larval lethal. Successful embryogenesis appears to be
      a consequence of maternal contribution of the complex. Biochemical analysis
      indicates that the different subunits are found in both CSN-dependent and CSN
      independent forms, and that these forms are differentially affected by the
      mutations. Phenotypic characterization of these two mutants indicates that they
      show both shared and unique phenotypes, which suggest specific roles for each
      subunit. Both mutants have defective oocyte and embryo patterning, and defects in
      response to DNA damage, while csn5 mutants develop melanotic tumors and csn4
      mutants have phenotypes reminiscent of defects in ecdysone signaling.

PMID- 12223401
TI  - An A-kinase anchoring protein is required for protein kinase A regulatory subunit
      localization and morphology of actin structures during oogenesis in Drosophila.
AB  - Protein kinase A (PKA) holoenzyme is anchored to specific subcellular regions by
      interactions between regulatory subunits (Pka-R) and A-kinase anchoring proteins
      (AKAPs). We examine the functional importance of PKA anchoring during Drosophila
      oogenesis by analyzing membrane integrity and actin structures in mutants with
      disruptions in Akap200, an AKAP. In wild-type ovaries, Pka-RII and Akap200
      localized to membranes and to the outer rim of ring canals, actin-rich structures
      that connect germline cells. In Akap200 mutant ovaries, Pka-RII membrane
      localization decreased, leading to a destabilization of membrane structures and
      the formation of binucleate nurse cells. Defects in membrane integrity could be
      mimicked by expressing a constitutively active PKA catalytic subunit (Pka-C)
      throughout germline cells. Unexpectedly, nurse cells in Akap200 mutant ovaries
      also had enlarged, thin ring canals. In contrast, overexpressing Akap200 in the
      germline resulted in thicker, smaller ring canals. To investigate the role of
      Akap200 in regulating ring canal growth, we examined genetic interactions with
      other genes that are known to regulate ring canal morphology. Akap200 mutations
      suppressed the small ring canal phenotype produced by Src64B mutants, linking
      Akap200 with the non-receptor tyrosine kinase pathway. Together, these results
      provide the first evidence that PKA localization is required for morphogenesis of
      actin structures in an intact organism.

PMID- 12223400
TI  - The repressor activity of Even-skipped is highly conserved, and is sufficient to
      activate engrailed and to regulate both the spacing and stability of parasegment
      boundaries.
AB  - During segmentation of the Drosophila embryo, even skipped is required to
      activate engrailed stripes and to organize odd-numbered parasegments. A 16 kb
      transgene containing the even skipped coding region can rescue normal engrailed
      expression, as well as all other aspects of segmentation, in even skipped null
      mutants. To better understand its mechanism of action, we functionally dissected
      the Even-skipped protein in the context of this transgene. We found that Even
      skipped utilizes two repressor domains to carry out its function. Each of these
      domains can function autonomously in embryos when fused with the Gal4 DNA-binding
      domain. A chimeric protein consisting only of the Engrailed repressor domain and
      the Even-skipped homeodomain, but not the homeodomain alone, was able to restore
      function, indicating that the repression of target genes is sufficient for even
      skipped function at the blastoderm stage, while the homeodomain is sufficient to
      recognize those target genes. When Drosophila Even skipped was replaced by its
      homologs from other species, including a mouse homolog, they could provide
      substantial function, indicating that these proteins can recognize similar target
      sites and also provide repressor activity. Using this rescue system, we show that
      broad, early even skipped stripes are sufficient for activation of both odd- and
      even-numbered engrailed stripes. Furthermore, these 'unrefined' stripes organize
      odd-numbered parasegments in a dose-dependent manner, while the refined, late
      stripes, which coincide cell-for-cell with parasegment boundaries, are required
      to ensure the stability of the boundaries.

PMID- 12223402
TI  - BMP signaling is required for development of the ciliary body.
AB  - The ciliary body in the eye secretes aqueous humor and glycoproteins of the
      vitreous body and maintains the intraocular pressure. The ciliary muscle controls
      the shape of the lens through the ciliary zonules to focus the image onto the
      retina. During embryonic development, the ciliary epithelium is derived from the
      optic vesicle, but the molecular signals that control morphogenesis of the
      ciliary body are unknown. We report that lens-specific expression of a transgenic
      protein, Noggin, can block BMP signaling in the mouse eye and result in failure
      in formation of the ciliary processes. Co-expression of transgenic BMP7 restores
      normal development of the ciliary epithelium. Ectopic expression of Noggin also
      promotes differentiation of retinal ganglion cells. These results indicate that
      BMP signaling is required for development of the ciliary body and may also play a
      role in regulation of neuronal differentiation in the developing eye.

PMID- 12223403
TI  - Specification of an anterior neuroectoderm patterning by Frizzled8a-mediated
      Wnt8b signalling during late gastrulation in zebrafish.
AB  - Wnts have been shown to provide a posteriorizing signal that has to be repressed
      in the anterior neuroectoderm for normal anteroposterior (AP) patterning. We have
      previously identified a zebrafish frizzled8a (fz8a) gene expressed in the
      presumptive anterior neuroectoderm as well as prechordal plate at the late
      gastrula stage. We have investigated the role of Fz8a-mediated Wnt8b signalling
      in anterior brain patterning in zebrafish. We show that in zebrafish embryos: (1)
      Wnt signalling has at least two different stage-specific posteriorizing
      activities in the anterior neuroectoderm, one before mid-gastrulation and the
      other at late gastrulation; (2) Fz8a plays an important role in mediating
      anterior brain patterning; (3) Wnt8b and Fz8a can functionally interact to
      transmit posteriorizing signals that determine the fate of the posterior
      diencephalon and midbrain in late gastrula embryos; and (4) Wnt8b can suppress
      fz8a expression in the anterior neuroectoderm and potentially affect the level
      and/or range of Wnt signalling. In conclusion, we suggest that a gradient of Fz8a
      mediated Wnt8b signalling may play crucial role in patterning the posterior
      diencephalon and midbrain regions in the late gastrula.

PMID- 12223404
TI  - Requirement for endoderm and FGF3 in ventral head skeleton formation.
AB  - The vertebrate head skeleton is derived in part from neural crest cells, which
      physically interact with head ectoderm, mesoderm and endoderm to shape the
      pharyngeal arches. The cellular and molecular nature of these interactions is
      poorly understood, and we explore here the function of endoderm in this process.
      By genetic ablation and reintroduction of endoderm in zebrafish, we show that it
      is required for the development of chondrogenic neural crest cells, including
      their identity, survival and differentiation into arch cartilages. Using a
      genetic interference approach, we further identify Fgf3 as a critical component
      of endodermal function that allows the development of posterior arch cartilages.
      Together, our results reveal for the first time that the endoderm provides
      differential cues along the anteroposterior axis to control ventral head skeleton
      development and demonstrate that this function is mediated in part by Fgf3.

PMID- 12223405
TI  - LET-99 determines spindle position and is asymmetrically enriched in response to
      PAR polarity cues in C. elegans embryos.
AB  - Asymmetric cell division depends on coordinating the position of the mitotic
      spindle with the axis of cellular polarity. We provide evidence that LET-99 is a
      link between polarity cues and the downstream machinery that determines spindle
      positioning in C. elegans embryos. In let-99 one-cell embryos, the nuclear
      centrosome complex exhibits a hyperactive oscillation that is dynein dependent,
      instead of the normal anteriorly directed migration and rotation of the nuclear
      centrosome complex. Furthermore, at anaphase in let-99 embryos the spindle poles
      do not show the characteristic asymmetric movements typical of wild type animals.
      LET-99 is a DEP domain protein that is asymmetrically enriched in a band that
      encircles P lineage cells. The LET-99 localization pattern is dependent on PAR
      polarity cues and correlates with nuclear rotation and anaphase spindle pole
      movements in wild-type embryos, as well as with changes in these movements in par
      mutant embryos. In particular, LET-99 is uniformly localized in one-cell par-3
      embryos at the time of nuclear rotation. Rotation fails in spherical par-3
      embryos in which the eggshell has been removed, but rotation occurs normally in
      spherical wild-type embryos. The latter results indicate that nuclear rotation in
      intact par-3 embryos is dictated by the geometry of the oblong egg and are
      consistent with the model that the LET-99 band is important for rotation in wild
      type embryos. Together, the data indicate that LET-99 acts downstream of PAR-3
      and PAR-2 to determine spindle positioning, potentially through the asymmetric
      regulation of forces on the spindle.

PMID- 12223406
TI  - MAPK-upstream protein kinase (MUK) regulates the radial migration of immature
      neurons in telencephalon of mouse embryo.
AB  - The radial migration of differentiating neurons provides an essential step in the
      generation of laminated neocortex, although its molecular mechanism is not fully
      understood. We show that the protein levels of a JNK activator kinase,
      MUK/DLK/ZPK, and JNK activity increase potently and temporally in newly generated
      neurons in developing mouse telencephalon during radial migration. The ectopic
      expression of MUK/DLK/ZPK in neural precursor cells in utero impairs radial
      migration, whereas it allows these cells to leave the ventricular zone and
      differentiate into neural cells. The MUK/DLK/ZPK protein is associated with
      dotted structures that are frequently located along microtubules and with Golgi
      apparatus in cultured embryonic cortical cells. In COS-1 cells, MUK/DLK/ZPK
      overexpression impairs the radial organization of microtubules without massive
      depolymerization. These results suggest that MUK/DLK/ZPK and JNK regulate radial
      cell migration via microtubule-based events.

PMID- 12223407
TI  - Drosophila myb exerts opposing effects on S phase, promoting proliferation and
      suppressing endoreduplication.
AB  - Drosophila melanogaster possesses a single gene, Dm myb, that is closely related
      to the vertebrate family of Myb genes, which encode transcription factors that
      are involved in regulatory decisions affecting cell proliferation,
      differentiation and apoptosis. The vertebrate Myb genes have been specifically
      implicated in regulating the G(1)/S transition of the cell cycle. Dm myb is
      expressed in all proliferating tissues, but not at detectable levels in
      endoreduplicating cells. Analysis of loss-of-function mutations in Dm myb
      revealed a block at the G(2)/M transition and mitotic defects, but did not
      directly implicate Dm myb function in the G(1/)S transition. We have used the
      Gal4-UAS binary system of ectopic expression to further investigate the function
      of Dm myb. Our results demonstrate that depending upon the type of cell cycle,
      ectopic Dm myb activity can exert opposing effects on S phase: driving DNA
      replication and promoting proliferation in diploid cells, even when developmental
      signals normally dictate cell cycle arrest; but suppressing endoreduplication in
      endocycling cells, an effect that can be overcome by induction of E2F. We also
      show that a C-terminally truncated DMyb protein, which is similar to an oncogenic
      form of vertebrate Myb, has more potent effects than the full-length protein,
      especially in endoreduplicating tissues. This finding indicates that the C
      terminus acts as a negative regulatory domain, which can be differentially
      regulated in a tissue-specific manner. Our studies help to resolve previous
      discrepancies regarding myb gene function in Drosophila and vertebrates. We
      conclude that in proliferating cells, Dm myb has the dual function of promoting S
      phase and M phase, while preserving diploidy by suppressing endoreduplication.

PMID- 12223408
TI  - Heart tube patterning in Drosophila requires integration of axial and segmental
      information provided by the Bithorax Complex genes and hedgehog signaling.
AB  - The Drosophila larval cardiac tube is composed of 104 cardiomyocytes that exhibit
      genetic and functional diversity. The tube is divided into the aorta and the
      heart proper that encompass the anterior and posterior parts of the tube,
      respectively. Differentiation into aorta and heart cardiomyocytes takes place
      during embryogenesis. We have observed living embryos to correlate morphological
      changes occurring during the late phases of cardiogenesis with the acquisition of
      organ function, including functional inlets, or ostiae. Cardiac cells diversity
      originates in response to two types of spatial information such that cells
      differentiate according to their position, both within a segment and along the
      anteroposterior axis. Axial patterning is controlled by homeotic genes of the
      Bithorax Complex (BXC) which are regionally expressed within the cardiac tube in
      non-overlapping domains. Ultrabithorax (Ubx) is expressed in the aorta whereas
      abdominal A (abd-A) is expressed in the heart, with the exception of the four
      most posterior cardiac cells which express Abdominal B (Abd-B). Ubx and abd-A
      functions are required to confer an aorta or a heart identity on cardiomyocytes,
      respectively. The anterior limit of the expression domain of Ubx, abd-A and Abd-B
      is independent of the function of the other genes. In contrast, abd-A represses
      Ubx expression in the heart and ectopic overexpression of abd-A transforms aorta
      cells into heart cardiomyocytes. Taken together, these results support the idea
      that BXC homeotic genes in the cardiac tube conform to the posterior prevalence
      rule. The cardiac tube is also segmentally patterned and each metamere contains
      six pairs of cardioblasts that are genetically diverse. We show that the
      transcription of seven up (svp), which is expressed in the two most posterior
      pairs of cardioblasts in each segment, is dependent on hedgehog (hh) signaling
      from the dorsal ectoderm. In combination with the axial information furnished by
      abd-A, the segmental hh-dependent information leads to the differentiation of the
      six pairs of svp-expressing cells into functional ostiae.

PMID- 12223409
TI  - Signaling from germ cells mediated by the rhomboid homolog stet organizes
      encapsulation by somatic support cells.
AB  - Germ cells normally differentiate in the context of encapsulating somatic cells.
      However, the mechanisms that set up the special relationship between germ cells
      and somatic support cells and the signals that mediate the crucial communications
      between the two cell types are poorly understood. We show that interactions
      between germ cells and somatic support cells in Drosophila depend on wild-type
      function of the stet gene. In males, stet acts in germ cells to allow their
      encapsulation by somatic cyst cells and is required for germ cell
      differentiation. In females, stet function allows inner sheath cells to enclose
      early germ cells correctly at the tip of the germarium. stet encodes a homolog of
      rhomboid, a component of the epidermal growth factor receptor signaling pathway
      involved in ligand activation in the signaling cell. The stet mutant phenotype
      suggests that stet facilitates signaling from germ cells to the epidermal growth
      factor receptor on somatic cells, resulting in the encapsulation of germ cells by
      somatic support cells. The micro-environment provided by the surrounding somatic
      cells may, in turn, regulate differentiation of the germ cells they enclose.

PMID- 12223410
TI  - Pax6 is required for establishing naso-temporal and dorsal characteristics of the
      optic vesicle.
AB  - The establishment of polarity is an important step during organ development. We
      assign a function for the paired and homeodomain transcription factor Pax6 in
      axis formation in the retina. Pax6 is a key factor of the highly conserved
      genetic network implicated in directing the initial phases of eye development. We
      recently demonstrated that Pax6 is also essential for later aspects of eye
      development, such as lens formation and retinogenesis. In this study, we present
      evidence that a highly conserved intronic enhancer, alpha, in the Pax6 gene is
      essential for the establishment of a distal(high)-proximal(low) gradient of Pax6
      activity in the retina. In the mature retina, the activity mediated by the alpha
      enhancer defines a population of retinal ganglion cells that project to two
      sickle-shaped domains in the superior colliculus and lateral geniculate nucleus.
      Deletion of the alpha-enhancer in vivo revealed that retinal Pax6 expression is
      regulated in two complementary topographic domains. We found that Pax6 activity
      is required for the establishment, as well as the maintenance of dorsal and
      nasotemporal characteristics in the optic vesicle and, later, the optic cup.

PMID- 12223411
TI  - Insulin-like growth factor binding protein-5 (IGFBP-5) induces premature cell
      death in the mammary glands of transgenic mice.
AB  - We have previously demonstrated that IGFBP-5 production by mammary epithelial
      cells increases dramatically during involution of the mammary gland. To
      demonstrate a causal relationship between IGFBP-5 and cell death we created
      transgenic mice expressing IGFBP-5 in the mammary gland using a mammary-specific
      promoter, beta-lactoglobulin. DNA content in the mammary glands of transgenic
      mice was decreased as early as day 10 of pregnancy. Histological analysis
      indicated reduced numbers of alveolar end buds, with decreased ductal branching.
      Transgenic dams produced IGFBP-5 in their milk at concentrations similar to those
      achieved at the end of normal lactation. Mammary cell number and milk synthesis
      were both decreased by approximately 50% during the first 10 days of lactation.
      BrdU labelling was decreased, whereas DNA ladders were increased in transgenic
      animals on day 1 of lactation. On day 2 postpartum, the epithelial invasion of
      the mammary fat pad was clearly impaired in transgenic animals. The
      concentrations of the pro-apoptotic molecule caspase-3 and of plasmin were both
      increased in transgenic animals whilst the concentrations of 2 prosurvival
      molecules Bcl-2 and Bcl-x(L)were both decreased. In order to examine whether
      IGFBP-5 acts by inhibiting the survival effect of IGF-I we examined IGF receptor
      phosphorylation and Akt phosphorylation and showed that both were inhibited. We
      attempted to "rescue" the transgenic phenotype by using growth hormone to
      increase endogenous IGF-I concentrations or by implanting minipumps delivering an
      IGF-1 analogue, R(3)-IGF-1, which binds weakly to IGFBP-5. Growth hormone
      treatment failed to affect mammary development suggesting that increased
      concentrations of endogenous IGF-1 are insufficient to overcome the high
      concentrations of IGFBP-5 produced by these transgenic animals. In contrast
      mammary development (gland weight and DNA content) was normalised by R3-IGF-I
      although milk production was only partially restored. This is the first
      demonstration that over-expression of IGFBP-5 can lead to; impaired mammary
      development, increased expression of the pro-apoptotic molecule caspase-3,
      increased plasmin generation and decreased expression of pro-survival molecules
      of the Bcl-2 family. It clearly demonstrates that IGF-I is an important
      developmental/survival factor for the mammary gland and, furthermore, this cell
      death programme may be utilised in a wide variety of tissues.

PMID- 12223412
TI  - FGFR4 signaling is a necessary step in limb muscle differentiation.
AB  - In chick embryos, most if not all, replicating myoblasts present within the
      skeletal muscle masses express high levels of the FGF receptor FREK/FGFR4,
      suggesting an important role for this molecule during myogenesis. We examined
      FGFR4 function during myogenesis, and we demonstrate that inhibition of FGFR4,
      but not FGFR1 signaling, leads to a dramatic loss of limb muscles. All muscle
      markers analyzed (such as Myf5, MyoD and the embryonic myosin heavy chain) are
      affected. We show that inhibition of FGFR4 signal results in an arrest of muscle
      progenitor differentiation, which can be rapidly reverted by the addition of
      exogenous FGF, rather than a modification in their proliferative capacities.
      Conversely, over-expression of FGF8 in somites promotes FGFR4 expression and
      muscle differentiation in this tissue. Together, these results demonstrate that
      in vivo, myogenic differentiation is positively controlled by FGF signaling, a
      notion that contrasts with the general view that FGF promotes myoblast
      proliferation and represses myogenic differentiation. Our data assign a novel
      role to FGF8 during chick myogenesis and demonstrate that FGFR4 signaling is a
      crucial step in the cascade of molecular events leading to terminal muscle
      differentiation.

PMID- 12223413
TI  - The early epaxial enhancer is essential for the initial expression of the
      skeletal muscle determination gene Myf5 but not for subsequent, multiple phases
      of somitic myogenesis.
AB  - Vertebrate myogenesis is controlled by four transcription factors known as the
      myogenic regulatory factors (MRFs): Myf5, Mrf4, myogenin and MyoD. During mouse
      development Myf5 is the first MRF to be expressed and it acts by integrating
      multiple developmental signals to initiate myogenesis. Numerous discrete
      regulatory elements are involved in the activation and maintenance of Myf5 gene
      expression in the various muscle precursor populations, reflecting the diversity
      of the signals that control myogenesis. Here we focus on the enhancer that
      recapitulates the first phase of Myf5 expression in the epaxial domain of the
      somite, in order to identify the subset of cells that first transcribes the gene
      and therefore gain insight into molecular, cellular and anatomical facets of
      early myogenesis. Deletion of this enhancer from a YAC reporter construct that
      recapitulates the Myf5 expression pattern demonstrates that this regulatory
      element is necessary for expression in the early epaxial somite but in no other
      site of myogenesis. Importantly, Myf5 is subsequently expressed in the epaxial
      myotome under the control of other elements located far upstream of the gene. Our
      data suggest that the inductive signals that control Myf5 expression switch
      rapidly from those that impinge on the early epaxial enhancer to those that
      impinge on the other enhancers that act later in the epaxial somite, indicating
      that there are significant changes in either the signalling environment or the
      responsiveness of the cells along the rostrocaudal axis. We propose that the
      first phase of Myf5 epaxial expression, driven by the early epaxial enhancer in
      the dermomyotome, is necessary for early myotome formation, while the subsequent
      phases are associated with cytodifferentiation within the myotome.

PMID- 12223414
TI  - Expression of a mutant maize gene in the ventral leaf epidermis is sufficient to
      signal a switch of the leaf's dorsoventral axis.
AB  - Maize leaves are initiated from the shoot apex with an inherent leaf dorsoventral
      polarity; the leaf surface closest to the meristem is the adaxial (upper, dorsal)
      surface whereas the opposite leaf surface is the abaxial (lower, ventral)
      surface. The Rolled leaf1 (Rld1) semi-dominant maize mutations affect
      dorsoventral patterning by causing adaxialization of abaxial leaf regions. This
      adaxialization is sometimes associated with abaxialization of the adaxial leaf
      regions, which constitutes a "switch". Dosage analysis indicates Rld1 mutants are
      antimorphs. We mapped Rld1's action to a single cell layer using a mosaic
      analysis and show Rld1 acts non cell-autonomously along the dorsoventral axis.
      The presence of Rld1 mutant product in the abaxial epidermis is necessary and
      sufficient to induce the Rolled leaf1 phenotype within the lower epidermis as
      well as in other leaf layers along the dorsoventral axis. These results support a
      model for the involvement of wild-type RLD1 in the maintenance of dorsoventral
      features of the leaf. In addition, they demonstrate the abaxial epidermis
      sends/receives a cell fate determining signal to/from the adaxial epidermis and
      controls the dorsoventral patterning of the maize leaf.

PMID- 12223416
TI  - A genetic link between Tbx1 and fibroblast growth factor signaling.
AB  - Tbx1 haploinsufficiency causes aortic arch abnormalities in mice because of early
      growth and remodeling defects of the fourth pharyngeal arch arteries. The
      function of Tbx1 in the development of these arteries is probably cell non
      autonomous, as the gene is not expressed in structural components of the artery
      but in the surrounding pharyngeal endoderm. We hypothesized that Tbx1 may trigger
      signals from the pharyngeal endoderm directed to the underlying mesenchyme. We
      show that the expression patterns of Fgf8 and Fgf10, which partially overlap with
      Tbx1 expression pattern, are altered in Tbx1(-/-) mutants. In particular, Fgf8
      expression is abolished in the pharyngeal endoderm. To understand the
      significance of this finding for the pathogenesis of the mutant Tbx1 phenotype,
      we crossed Tbx1 and Fgf8 mutants. Double heterozygous Tbx1(+/-);Fgf8(+/-) mutants
      present with a significantly higher penetrance of aortic arch artery defects than
      do Tbx1(+/-);Fgf8(+/+) mutants, while Tbx1(+/+);Fgf8(+/-) animals are normal. We
      found that Fgf8 mutation increases the severity of the primary defect caused by
      Tbx1 haploinsufficiency, i.e. early hypoplasia of the fourth pharyngeal arch
      arteries, consistent with the time and location of the shared expression domain
      of the two genes. Hence, Tbx1 and Fgf8 interact genetically in the development of
      the aortic arch. Our data provide the first evidence of a genetic link between
      Tbx1 and FGF signaling, and the first example of a modifier of the Tbx1
      haploinsufficiency phenotype. We speculate that the FGF8 locus might affect the
      penetrance of cardiovascular defects in individuals with chromosome 22q11
      deletions involving TBX1.

PMID- 12223415
TI  - An Fgf8 mouse mutant phenocopies human 22q11 deletion syndrome.
AB  - Deletion of chromosome 22q11, the most common microdeletion detected in humans,
      is associated with a life-threatening array of birth defects. Although 90% of
      affected individuals share the same three megabase deletion, their phenotype is
      highly variable and includes craniofacial and cardiovascular anomalies,
      hypoplasia or aplasia of the thymus with associated deficiency of T cells,
      hypocalcemia with hypoplasia or aplasia of the parathyroids, and a variety of
      central nervous system abnormalities. Because ablation of neural crest in chicks
      produces many features of the deletion 22q11 syndrome, it has been proposed that
      haploinsufficiency in this region impacts neural crest function during cardiac
      and pharyngeal arch development. Few factors required for migration, survival,
      proliferation and subsequent differentiation of pharyngeal arch neural crest and
      mesoderm-derived mesenchyme into their respective cardiovascular,
      musculoskeletal, and glandular derivatives have been identified. However, the
      importance of epithelial-mesenchymal interactions and pharyngeal endoderm
      function is becoming increasingly clear. Fibroblast growth factor 8 is a
      signaling molecule expressed in the ectoderm and endoderm of the developing
      pharyngeal arches and known to play an important role in survival and patterning
      of first arch tissues. We demonstrate a dosage-sensitive requirement for FGF8
      during development of pharyngeal arch, pharyngeal pouch and neural crest-derived
      tissues. We show that FGF8 deficient embryos have lethal malformations of the
      cardiac outflow tract, great vessels and heart due, at least in part, to failure
      to form the fourth pharyngeal arch arteries, altered expression of Fgf10 in the
      pharyngeal mesenchyme, and abnormal apoptosis in pharyngeal and cardiac neural
      crest. The Fgf8 mutants described herein display the complete array of
      cardiovascular, glandular and craniofacial phenotypes seen in human deletion
      22q11 syndromes. This represents the first single gene disruption outside the
      typically deleted region of human chromosome 22 to fully recapitulate the
      deletion 22q11 phenotype. FGF8 may operate directly in molecular pathways
      affected by deletions in 22q11 or function in parallel pathways required for
      normal development of pharyngeal arch and neural crest-derived tissues. In either
      case, Fgf8 may function as a modifier of the 22q11 deletion and contribute to the
      phenotypic variability of this syndrome.

PMID- 12223417
TI  - Fgf8 is required for pharyngeal arch and cardiovascular development in the mouse.
AB  - We present here an analysis of cardiovascular and pharyngeal arch development in
      mouse embryos hypomorphic for Fgf8. Previously, we have described the generation
      of Fgf8 compound heterozygous (Fgf8(neo/-)) embryos. Although early analysis
      demonstrated that some of these embryos have abnormal left-right (LR) axis
      specification and cardiac looping reversals, the number and type of cardiac
      defects present at term suggested an additional role for Fgf8 in cardiovascular
      development. Most Fgf8(neo/-) mutant embryos survive to term with abnormal
      cardiovascular patterning, including outflow tract, arch artery and intracardiac
      defects. In addition, these mutants have hypoplastic pharyngeal arches, small or
      absent thymus and abnormal craniofacial development. Neural crest cells (NCCs)
      populate the pharyngeal arches and contribute to many structures of the face,
      neck and cardiovascular system, suggesting that Fgf8 may be required for NCC
      development. Fgf8 is expressed within the developing pharyngeal arch ectoderm and
      endoderm during NCC migration through the arches. Analysis of NCC development in
      Fgf8(neo/-) mutant embryos demonstrates that NCCs are specified and migrate, but
      undergo cell death in areas both adjacent and distal to where Fgf8 is normally
      expressed. This study defines the cardiovascular defects present in Fgf8 mutants
      and supports a role for Fgf8 in development of all the pharyngeal arches and in
      NCC survival.

PMID- 12223418
TI  - Gonadal differentiation, sex determination and normal Sry expression in mice
      require direct interaction between transcription partners GATA4 and FOG2.
AB  - In mammals, Sry expression in the bipotential, undifferentiated gonad directs the
      support cell precursors to differentiate as Sertoli cells, thus initiating the
      testis differentiation pathway. In the absence of Sry, or if Sry is expressed at
      insufficient levels, the support cell precursors differentiate as granulosa
      cells, thus initiating the ovarian pathway. The molecular mechanisms upstream and
      downstream of Sry are not well understood. We demonstrate that the transcription
      factor GATA4 and its co-factor FOG2 are required for gonadal differentiation.
      Mouse fetuses homozygous for a null allele of Fog2 or homozygous for a targeted
      mutation in Gata4 (Gata4(ki)) that abrogates the interaction of GATA4 with FOG co
      factors exhibit abnormalities in gonadogenesis. We found that Sry transcript
      levels were significantly reduced in XY Fog2(-/-) gonads at E11.5, which is the
      time when Sry expression normally reaches its peak. In addition, three genes
      crucial for normal Sertoli cell function (Sox9, Mis and Dhh) and three Leydig
      cell steroid biosynthetic enzymes (p450scc, 3betaHSD and p450c17) were not
      expressed in XY Fog2(-/-) and Gata(ki/ki) gonads, whereas Wnt4, a gene required
      for normal ovarian development, was expressed ectopically. By contrast, Wt1 and
      Sf1, which are expressed prior to Sry and necessary for gonad development in both
      sexes, were expressed normally in both types of mutant XY gonads. These results
      indicate that GATA4 and FOG2 and their physical interaction are required for
      normal gonadal development.

PMID- 12223419
TI  - The heartstrings mutation in zebrafish causes heart/fin Tbx5 deficiency syndrome.
AB  - Holt-Oram syndrome is one of the autosomal dominant human "heart-hand" disorders,
      with a combination of upper limb malformations and cardiac defects. Holt-Oram
      syndrome is caused by mutations in the TBX5 gene, a member of a large family of T
      box transcription factors that play important roles in cell-type specification
      and morphogenesis. In a screen for mutations affecting zebrafish cardiac
      function, we isolated the recessive lethal mutant heartstrings, which lacks
      pectoral fins and exhibits severe cardiac dysfunction, beginning with a slow
      heart rate and progressing to a stretched, non-functional heart. We mapped and
      cloned the heartstrings mutation and find it to encode the zebrafish ortholog of
      the TBX5 gene. The heartstrings mutation causes premature termination at amino
      acid 316. Homozygous mutant embryos never develop pectoral fin buds and do not
      express several markers of early fin differentiation. The total absence of any
      fin bud differentiation distinguishes heartstrings from most other mutations that
      affect zebrafish fin development, suggesting that Tbx5 functions very early in
      the pectoral fin induction pathway. Moderate reduction of Tbx5 by morpholino
      causes fin malformations, revealing an additional early requirement for Tbx5 in
      coordinating the axes of fin outgrowth. The heart of heartstrings mutant embryos
      appears to form and function normally through the early heart tube stage,
      manifesting only a slight bradycardia compared with wild-type siblings. However,
      the heart fails to loop and then progressively deteriorates, a process affecting
      the ventricle as well as the atrium. Relative to mammals, fish require lower
      levels of Tbx5 to produce malformed appendages and display whole-heart rather
      than atrial-predominant cardiac defects. However, the syndromic deficiencies of
      tbx5 mutation are remarkably well retained between fish and mammals.

PMID- 12223420
TI  - Endogenous bone morphogenetic proteins regulate outgrowth and epithelial survival
      during avian lip fusion.
AB  - Our expression studies of bone morphogenetic proteins (BMPs) and Noggin (a BMP
      antagonist) in the embryonic chicken face suggested that BMP signals were
      important for closure of the upper lip or primary palate. We noted that Noggin
      expression was restricted to the frontonasal mass epithelium but was reduced at
      the corners of the frontonasal mass (globular processes) just prior to fusion
      with the adjacent maxillary prominences. We therefore performed gain- and loss-of
      function experiments to determine the role of BMPs in lip formation. Noggin
      treatment led to reduced proliferation and outgrowth of the frontonasal mass and
      maxillary prominences and ultimately to the deletion of the maxillary and
      palatine bones. The temporary block in BMP signalling in the mesenchyme also
      promoted epithelial survival. Noggin treatment also upregulated expression of
      endogenous BMPs, therefore we investigated whether increasing BMP levels would
      lead to the same phenotype. A BMP2 bead was implanted into the globular process
      and a similar phenotype to that produced by Noggin resulted. However, instead of
      a decrease in proliferation, defects were caused by increased programmed cell
      death, first in the epithelium and then in the mesenchyme. Programmed cell death
      was induced primarily in the lateral frontonasal mass with very little cell death
      medial to the bead. The asymmetric cell death pattern was correlated with a rapid
      induction of Noggin in the same embryos, with transcripts complementary to the
      regions with increased cell death. We have demonstrated a requirement for
      endogenous BMP in the proliferation of facial mesenchyme and that mesenchymal
      signals promote either survival or thinning of the epithelium. We furthermore
      demonstrated in vivo that BMP homeostasis is regulated by increasing expression
      of ligand or antagonist and that such mechanisms may help to protect the embryo
      from changes in growth factor levels during development or after exposure to
      teratogens.

PMID- 12223422
TI  - Consumption of animal foods, cooking methods, and risk of breast cancer.
AB  - Cumulative evidence suggests a possible interaction of cooking methods with diet
      in the pathogenesis of breast cancer. Studies, however, are few and inconsistent.
      We evaluated the association of animal food intake and degree of browning by deep
      frying with breast cancer risk in a population-based case-control study conducted
      during 1996-1998 among Chinese women in Shanghai, a population with a
      traditionally low risk of breast cancer. Included in the study were 1459 cases
      and 1556 age-frequency-matched controls with response rates of 91.1 and 90.3%,
      respectively. A validated food frequency questionnaire was used to obtain
      information on usual intake of animal foods and cooking oils and usual cooking
      methods. Increasing intake of red meat and freshwater fish was related to a
      moderately elevated risk of breast cancer risk. Stratified analyses showed that
      the positive association with red meat intake was primarily restricted to those
      who used deep-frying cooking method, particularly among those who deep-fried
      foods to well-done (odds ratio, 1.92; 95% confidence interval, 1.30-2.83 for the
      highest versus the lowest quintile; P for trend, 0.002). On the other hand, high
      intake of nonhydrogenated soybean cooking oil was related to a reduced risk of
      breast cancer among women who never deep-fried animal foods (odds ratio, 0.48;
      95% confidence interval, 0.28-0.82 for the highest versus the lowest quintile; P
      for trend, 0.02). The positive association of breast cancer risk with red meat
      intake, especially well-done red meat, was more pronounced among women with a
      high body mass index than those without this risk factor, and the test for
      multiplicative interaction was statistically significant. This study suggests
      that high intake of deep-fried, well-done red meat may be associated with an
      increased risk of breast cancer, and the positive association may be modified by
      body weight. This study also suggests that nonhydrogenated soybean oil, if not
      used in high-temperature cooking, may be associated with a reduced risk of breast
      cancer.

PMID- 12223421
TI  - Breast cancer in a multiethnic cohort in Hawaii and Los Angeles: risk factor
      adjusted incidence in Japanese equals and in Hawaiians exceeds that in whites.
AB  - Few data exist on the extent to which the differences in breast cancer risk
      between "racial-ethnic" groups in the United States (US) are "explained" by
      differences in their distribution of risk factors. We have determined this for
      African-American (AA), native Hawaiian (NH), Japanese-American (JA), Latina-US
      born (L-US), Latina-non-US-born (L-NUS), and white (W) women using prospective
      incidence data on 88,712 postmenopausal women recruited in 1993-1996. We
      identified 1,757 incident breast cancer cases through 1999 among these women
      (1,116 cases after excluding women with a simple hysterectomy or missing risk
      factor data). Data were available on seven "known" risk factors: ages at menarche
      and first birth; parity; age at and type of menopause; weight; hormone
      replacement therapy use; and alcohol consumption. The relative risks (RRs) of
      breast cancer (with the RR in Ws set to 1.0) for the groups were as follows: W =
      1.0; AA = 0.78; NH = 1.33; JA = 0.99; L-US = 0.77; and L-NUS = 0.60. After
      adjustment for the risk factors, the RRs were as follows: W = 1.0; AA = 0.98; NH
      = 1.65; JA = 1.11; L-US = 0.95; and L-NUSB = 0.84. The slightly greater risk of
      the JAs compared with the Ws is in sharp contrast to the very low breast cancer
      rates that were observed in "traditional" Japanese women and in early Japanese
      migrants. The adjusted RR of NHs is 65% greater than that of Ws, and that of
      migrant Latinas is 16% lower than that of Ws. Elucidating the causes of the high
      rates in NHs is now a major focus of our efforts.

PMID- 12223423
TI  - Comparison of techniques for the successful detection of BRCA1 mutations in fixed
      paraffin-embedded tissue.
AB  - Genomic DNA isolated from archived paraffin-embedded tissues (PETs) has important
      applicability in genetic epidemiological studies. To determine the accuracy of
      the sequence data, using DNA derived from PET among patients with known mutations
      characterized from blood, we conducted a blinded factorial experiment to
      simultaneously examine the influence of mutation type, age of the PET, PCR
      product type, and Taq DNA polymerase on BRCA1 gene mutation detection. The
      probability of detecting sequencing artifacts was also investigated. We found
      that: (a) gene detection was most accurate for newer PET; (b) high fidelity Taq
      with shorter PCR amplicon length yielded the highest mutation detection success
      rate and lowest artifact rate; and (c) base substitutions were more often
      correctly identified than frameshift mutations or wild-type sequences. We
      concluded that DNA derived from PET that archived for less than 18 years can be
      used successfully for detecting BRCA1 gene mutations if quality control is
      strictly maintained.

PMID- 12223424
TI  - Urinary excretion of phytoestrogens and risk of breast cancer among Chinese women
      in Shanghai.
AB  - Although the majority of ecological and experimental studies have suggested a
      potential role of phytoestrogens in breast cancer prevention, findings from
      epidemiological studies have been inconsistent. Part of the inconsistencies may
      be attributable to the difficulty in measuring intake levels of phytoestrogens.
      Overnight urine samples from 250 incident breast cancer cases and their
      individually matched controls were analyzed for urinary excretion rates of
      isoflavonoids, mammalian lignans, and citrus flavonoids. The study subjects were
      a subset of the participants in the Shanghai Breast Cancer Study, a large
      population-based case-control study conducted in Shanghai from 1996-1998. To
      minimize potential influence of treatment on the exposure of interest, urine
      samples from breast cancer cases were collected before cancer therapy. Urinary
      excretion of total isoflavonoids and mammalian lignans was substantially lower in
      breast cancer cases than in controls. The median excretion rate of total
      isoflavonoids was 13.97 nmol/mg creatinine in cases and 23.09 in controls (P =
      0.01), and the median excretion rate of total lignans was 1.77 in cases and 4.16
      in controls (P < 0.01). The risk of breast cancer was reduced with increasing
      excretion of total isoflavonoids (P for trend, 0.04) and total lignans (P for
      trend, <0.01), with adjusted odds ratios of 0.62 (95% confidence interval, 0.39
      0.99) and 0.40 (95% confidence interval, 0.24-0.64) observed for the highest
      versus the lowest tertile of total isoflavonoid and lignan excretion,
      respectively. The adjusted odds ratio was 0.28 (95% confidence interval, 0.15
      0.50) for women who had a high excretion rate of both total lignans and
      isoflavonoids compared with those with a low excretion of both groups of
      phytoestrogens. No association was observed with citrus flavonoids. The results
      from this study suggest that high intake of certain phytoestrogens may reduce the
      risk of breast cancer.

PMID- 12223425
TI  - Body mass index, height, and the risk of ovarian cancer mortality in a
      prospective cohort of postmenopausal women.
AB  - Endogenous hormones may play a role in ovarian carcinogenesis. Postmenopausal
      obesity, although associated with higher circulating levels of estrogen and
      androgens, has not been linked consistently to ovarian cancer. The present study
      examined the relationship between body mass index (BMI), height, and ovarian
      cancer mortality among postmenopausal women in a large prospective mortality
      study of 300,537 women who were cancer free at enrollment in 1982 and had no
      history of hysterectomy or ovarian surgery. During 16 years of follow-up, 1,511
      deaths occurred from ovarian cancer. Cox proportional hazard modeling was used to
      compute rate ratios (RRs) and to adjust for confounders. Ovarian cancer mortality
      rates were higher among overweight [BMI >/=25;RR, 1.16; 95% confidence interval
      (CI), 1.04-1.30] and obese women (BMI >/=30; RR, 1.26; 95% CI, 1.07-1.48)
      compared with women with BMI <25. Use of postmenopausal estrogens modified the
      association between BMI and ovarian cancer mortality (P = 0.05). The increased
      risk associated with obesity (BMI >/=30) was limited to women who never used
      postmenopausal estrogens (RR, 1.36; 95% CI, 1.12-1.66) and was not seen among
      ever users (RR, 0.93; 95% CI, 0.62-1.41). Height was positively associated with
      ovarian cancer mortality. Compared with women 152-156 cm tall, ovarian cancer
      mortality rates were lowest for the shortest women (RR, 0.72; 95% CI, 0.47-1.10
      for women <152 cm) and highest for the tallest (RR, 1.41; 95% CI, 0.95-2.09 for
      women >/=177 cm). In this study, obesity and height appear to be independently
      associated with ovarian cancer mortality. The 36% increase in risk associated
      with obesity among women who had never used postmenopausal estrogens may have
      important public health implications because obesity is a growing problem in the
      United States.

PMID- 12223426
TI  - Environmental factors in relation to breast cancer characterized by p53 protein
      expression.
AB  - Findings from studies of cigarette smoking and low-dose ionizing radiation
      exposure and breast cancer are unclear. Laboratory studies indicate that both
      exposures can cause DNA damage, potentially increasing cancer risk if such
      mutations occur in growth control genes, such as p53. We examined the potential
      etiologic heterogeneity of breast cancer by evaluating whether associations
      between cigarette smoking and low-dose ionizing radiation and breast cancer
      differed by p53 protein expression status. Data were obtained from the Carolina
      Breast Cancer Study, a population-based, case-control study conducted among
      African-American and white women ages 20-74 years. Questionnaire data were
      available from 861 women with incident, primary invasive breast cancer and 790
      community-based controls. p53 immunostaining was performed on tissue from 683
      women with breast cancer; 46% were classified as p53+. Two separate unconditional
      logistic regression models were used to calculate odds ratios (ORs) for p53+ and
      p53- breast cancer, as compared with controls, in relation to smoking and low
      dose ionizing radiation exposure. Smoking was not differentially associated with
      p53+ or p53- breast cancer, even when duration, dose, and passive smoking status
      were considered. Exposure to individual sources of radiation did not differ for
      p53+ and p53- breast cancers. However, ORs for combined exposure to chest X-rays
      and occupational radiation were higher for p53+ [OR, 2.2; 95% confidence interval
      (CI), 1.0-5.3] than p53- breast cancer (OR, 1.2; 95% CI, 0.5-3.4). Combined
      exposure to radiation from other medical sources as well as occupational exposure
      was also higher for p53+ (OR, 3.7; 95% CI, 0.8-16.8) than for p53- breast cancer
      (OR, 1.7; 95% CI, 0.3-10.5). Although preliminary, our results suggest that
      exposure to multiple sources of low-dose ionizing radiation may contribute to the
      development of p53+ breast cancer.

PMID- 12223427
TI  - Weight-cycling decreases incidence and increases latency of mammary tumors to a
      greater extent than does chronic caloric restriction in mouse mammary tumor virus
      transforming growth factor-alpha female mice.
AB  - Multiple periods of caloric restriction (or fasting)/refeeding in rodents have
      had inconsistent effects on mammary tumor (MT) development. In the present study,
      the consequence of intermittent caloric restriction/refeeding resulting in weight
      cycling was evaluated using an oncogene-induced MT mouse model. Hybrid mouse MT
      virus-transforming growth factor alpha (MMTV-TGF-alpha)/Lep(+)Lep(ob) female mice
      were used. Ad libitum-fed mice (n = 30) were fed American Institute of Nutrition
      (AIN)-93M diet. Beginning at 10 weeks of age, weight-cycled mice (n = 30) were
      fed an AIN-93 modified diet (2-fold increase in protein, fat, vitamin, and
      mineral contents) at 50% of ad libitum for 3-week intervals followed by 3-week
      intervals of ad libitum feeding using AIN-93M diet. Pair-fed mice (n = 33), were
      fed a 2:1 mixture of AIN-93M:AIN-93 modified diets to match the caloric intake of
      weight-cycled mice for each 6-week age-matched caloric restriction/refeeding
      interval. Food intakes were determined daily and body weights weekly. Mice were
      euthanized when MTs exceeded 20 mm in length or at 80 weeks of age. Final body
      weights were similar, but cumulative food intake of ad libitum-fed mice was 21%
      greater than that of the other groups. Ad libitum-fed mice had a 77% MT incidence
      versus 3% for weight-cycled and 44% for pair-fed mice. MTs were detected earlier
      for ad libitum-fed mice, 64.1 weeks versus 73.5 weeks for pair-fed mice. The only
      MT in one weight-cycled mouse was excised at necropsy (80 weeks of age) and
      weighed only 0.063 g. Average MT weight for ad libitum-fed mice was 1.034 g and
      for pair-fed mice was 0.667 g. Intervals of caloric restriction/refeeding
      resulting in weight-cycling were protective against MT development in this mouse
      model. Future studies should address the application of this intervention to
      additional transgenic mice as well as other MT models.

PMID- 12223428
TI  - Soy intake and other lifestyle determinants of serum estrogen levels among
      postmenopausal Chinese women in Singapore.
AB  - Endogenous estrogen levels are strongly associated with breast cancer risk, but
      its determinants are not well understood. We conducted a cross-sectional study of
      144 healthy postmenopausal women, participants in a population-based prospective
      investigation of diet and cancer risk among Chinese in Singapore. The
      relationships between plasma levels of estrone (E(1)), estradiol (E(2)), and
      androstenedione and dietary intake of soy and other food groups were
      investigated. Data on diet and other lifestyle factors were obtained from a
      structured questionnaire with a validated dietary component that was administered
      in-person to all participants. Few dietary factors emerged as determinants of
      plasma estrogen levels in this population. An exception was soy, which was
      significantly associated with plasma E(1) levels. Specifically, E(1) levels were
      15% lower among individuals in the highest quartile of soy protein intake
      compared with those in the lower three quartiles of intake (P = 0.047). E(1)
      levels did not differ between individuals in the lower three quartiles of soy
      protein intake. Similar patterns of differences in E(1) levels emerged in
      analyses by intake of isoflavones and total soy products. These findings on soy
      were independent of the four nondietary factors (see below) that significantly
      influenced estrogen levels. Both E(1) and E(2) levels increased with high body
      mass index [BMI (weight/height(2))]; the respective levels were 41% (two-sided P
      = 0.02) and 17% higher (P = 0.34) among women in the highest BMI category (BMI
      >/= 24) compared with those in the lowest category (BMI < 20). After adjustment
      for BMI and age, women with a late age at menarche (age 17 years or older) showed
      significantly lower E(1) (30% lower; P = 0.02) and E(2) levels (24% lower; P =
      0.02) compared with women with earlier age at menarche (before age 17 years) and
      who were nulliparous or had a late age at first live birth (after age 31 years).
      Current smokers showed significantly higher E(2) levels (28%) than nonsmokers (P
      = 0.04). These findings are discussed in relation to the recent doubling of
      breast cancer incidence among Chinese women in Singapore.

PMID- 12223429
TI  - Dietary correlates of plasma insulin-like growth factor I and insulin-like growth
      factor binding protein 3 concentrations.
AB  - Plasma levels of insulin-like growth factor I (IGF-I) have been associated with
      risk of several cancers. Although protein-calorie malnutrition is known to
      decrease IGF-I levels, few published studies have related diet to IGF-I levels in
      well-nourished humans. We examined the cross-sectional association of plasma IGF
      I and IGF-binding protein 3 (IGFBP-3) levels with intakes of alcohol, energy,
      macronutrients, micronutrients, and specific foods in 1037 healthy women.
      Adjusted mean hormone levels across categories of dietary variables were
      calculated by linear regression. Results were adjusted for non-dietary factors
      found to be associated with IGF levels. Total energy intake was positively
      associated with IGF-I levels when adjusted for covariates. Adjusted mean levels
      of IGF-I (ng/ml) across increasing quintiles of energy intake were 181, 185, 191,
      199, and 195 (P for the linear trend = 0.006). In other multivariate analyses,
      energy-adjusted fat and carbohydrate intake had no association with IGF-I levels.
      The most consistent finding was a positive association between protein intake
      with circulating IGF-I concentration (174, 188, 201, 192, and 196 ng/ml across
      quintiles of protein intake; P = 0.002), which was largely attributable to milk
      intake. Adjusted mean levels of IGF-I (ng/ml) across increasing quartiles of milk
      intake were 183, 189, 188, and 200 (P = 0.01). Higher fat intake, in particular
      saturated fat, was associated with lower levels of IGFBP-3. We conclude that
      higher energy, protein, and milk intakes were associated with higher levels of
      IGF-I. These associations raise the possibility that diet could affect cancer
      risk through influencing IGF-I level.

PMID- 12223430
TI  - Lifestyle correlates of plasma insulin-like growth factor I and insulin-like
      growth factor binding protein 3 concentrations.
AB  - Plasma levels of insulin-like growth factor I (IGF-I) have been associated with
      risk of a number of cancers and other diseases. We examined the cross-sectional
      association of plasma IGF-I and IGF-binding protein 3 (IGFBP-3) levels with age,
      smoking, physical activity, and reproductive and menopausal factors in 1037
      healthy women. Adjusted least-square mean hormone levels across categories of
      lifestyle factors were calculated by linear regression. Age was inversely
      associated with IGF-I levels. In multivariate analyses, a higher body mass index
      (BMI) was associated with higher IGFBP-3 levels (BMI <21 versus >/=29 kg/m(2),
      3879 versus 4080 ng/ml; P for trend = 0.01). Current use of hormone replacement
      therapy (HRT) was associated with a lower IGF-I, with oral estrogen being
      associated with the lowest levels (non-use of HRT versus oral estrogen +
      progesterone versus oral estrogen: 181 versus 143 versus 116 ng/ml; P for all
      comparisons </= 0.005). Higher parity was also associated with lower levels of
      IGF-I (no pregnancies versus >/=4: 212 versus 180 ng/ml; P for trend = 0.003). We
      conclude that age and HRT use, particularly oral estrogen alone, were inversely
      associated with IGF-I levels. BMI was positively associated with IGFBP-3 levels.
      This is the first report of an inverse association of circulating IGF-I levels
      with parity. This association may represent one mechanism by which parity exerts
      its protective effect on some cancers.

PMID- 12223431
TI  - Identification of potential prostate cancer preventive agents through induction
      of quinone reductase in vitro.
AB  - Human prostate cancer is characterized by an early and near-universal loss of
      expression of the phase 2 enzyme glutathione S-transferase-pi (GSTP1). We
      hypothesize that a mechanism-based prostate cancer preventive strategy could
      involve induction of phase 2 enzymes within the prostate to compensate for the
      loss of GSTP1 expression. NAD[P]H:(quinone-acceptor) oxidoreductase (quinone
      reductase or QR) enzymatic activity, a surrogate of phase 2 enzyme response, was
      measured after treating the human prostate cancer cell line LNCaP with known
      phase 2 enzyme-inducing agents from 10 distinct chemical classes. QR enzymatic
      activity was assayed in microtiter plates using the menadione-coupled reduction
      of tetrazolium dye. Degree of induction was expressed as fold-increase over
      control and corrected for toxicity. Compounds were also tested in LNCaP-5-aza-C,
      an LNCaP subline selected in 5-aza-cytidine that expresses GSTP1, and in the
      human liver cell line HepG2. LNCaP showed robust induction of QR enzymatic
      activity after treatment with a subset of the phase 2 enzyme-inducing agents. All
      Michael acceptors were effective at inducing QR activity in LNCaP. Some phenolic
      antioxidants, heavy metal salts, and quinones also significantly increased QR
      activity, although inducer potency varied widely within these classes of
      compounds. Some of the isothiocyanates, mercaptans, bifunctional inducers, and
      trivalent arsenicals also produced modest QR induction, but peroxides and
      dithiolethiones were inactive. LNCaP-5-aza-C and LNCaP responded similarly to all
      compounds, but the pattern of response for HepG2 differed significantly. The
      differences in QR responsiveness between the prostate cell lines and HepG2
      suggest that prostate tissues may have a unique pattern of response to phase 2
      inducing agents distinct from other tissue types. Our data suggest that
      measurement of QR induction in prostate cancer cell lines may help identify
      potential cancer chemopreventive agents effective in the prostate.

PMID- 12223432
TI  - Vitamin A, carotenoids, and risk of persistent oncogenic human papillomavirus
      infection.
AB  - Oncogenic human papillomavirus (HPV) infection is the main etiologic factor for
      cervical neoplasia, although infection alone is insufficient to produce disease.
      Cofactors such as nutritional factors may be necessary for viral progression to
      neoplasia. Results from previous studies have suggested that higher dietary
      consumption and circulating levels of certain micronutrients may be protective
      against cervical neoplasia. This study evaluated the role of vitamin A and
      carotenoids on HPV persistence comparing women with intermittent and persistent
      infections. As determined by the Hybrid Capture II system, oncogenic HPV
      infections were assessed at baseline and at approximately 3 and 9 months
      postbaseline. Multivariate logistic regression analysis was used to determine the
      risk of persistent HPV infection associated with each tertile of dietary and
      circulating micronutrients. Higher levels of vegetable consumption were
      associated with a 54% decrease risk of HPV persistence (adjusted odds ratio,
      0.46; 95% confidence interval, 0.21-0.97). Also, a 56% reduction in HPV
      persistence risk was observed in women with the highest plasma cis-lycopene
      concentrations compared with women with the lowest plasma cis-lycopene
      concentrations (adjusted odds ratio, 0.44; 95% confidence interval, 0.19-1.01).
      These data suggest that vegetable consumption and circulating cis-lycopene may be
      protective against HPV persistence.

PMID- 12223433
TI  - Joint effect of genes and environment distorted by selection biases: implications
      for hospital-based case-control studies.
AB  - The hospital-based case-control design enhances the response rates in studies
      that require the collection of biological samples from all of the participants.
      There are simple, established criteria for selecting controls so as to estimate
      the effect of a single factor without bias, but the analogous requirements for
      assessing an interaction are less clear. We derive these conditions by
      calculating the potential bias from selecting controls who were admitted for
      treatment of diseases related to either or both of the exposures of interest,
      designated as a gene variant (G) and an environmental agent (E). There is no bias
      in the estimate of the effect of E when G is associated with the control
      condition, whether causally or because of confounding. There is no bias in
      estimating multiplicative interaction between G and E for the disease of interest
      when there is no multiplicative G-E interaction for the control disease, even
      when the control condition is caused by G or E; if a mixture of several control
      diseases are used, however, the absence of G-E interaction in each individual
      disease does not ensure a lack of overall bias when controls are pooled. Hospital
      control designs are much less robust for assessing additive interaction. We
      conclude that the ideal control disease in a hospital-based study of gene
      environment interaction is not caused by either G or E and that choosing controls
      from several conditions to act as a combined control group is a useful strategy.
      This formulation extends to the general problem of distortion of joint effects
      from selection biases or confounding.

PMID- 12223434
TI  - Genetic polymorphism of CYP2A6 gene and tobacco-induced lung cancer risk in male
      smokers.
AB  - Cytochrome P450 2A6 (CYP2A6) is the principal enzyme involved in the metabolic
      activation of tobacco-specific nitrosamines to their ultimate carcinogenic forms
      and metabolism of nicotine. We investigated the effects of the CYP2A6*4, an
      entire CYP2A6 gene deletion-type polymorphism, on lung cancer risk and daily
      cigarette consumption in Japanese male smokers via a hospital-based case control
      study. The frequency of the CYP2A6*4 variant was compared in 370 lung cancer
      patients and 380 control smokers. A markedly reduced adjusted odds ratio for lung
      cancer risk, 0.23 [95% confidence interval, 0.08-0.67], was seen in the group
      with homozygous deletion (*4/*4) when the odds ratio for a group with homozygous
      wild (*1A/*1A) was defined to be 1.00 by logistic regression. The subjects with
      lung cancer were additionally divided into three groups according to the
      histological classification of the cancer and examined for an association with
      the CYP2A6 polymorphism. The *4/*4 genotype was not found in patients with
      squamous cell carcinoma (0 of 105) or small cell carcinoma (0 of 44), indicating
      that subjects with the *4/*4 genotype have low risk for lung cancers,
      particularly those caused by tobacco smoke. Furthermore, a significant reduction
      of daily cigarette consumption was observed in smokers with the *4/*4 genotype,
      suggesting a possibility that complete lack of CYP2A6 appeared to affect the
      smoking behavior. These data suggest that male smokers possessing the *1A/*1A
      genotype have higher risk for tobacco-induced lung cancers.

PMID- 12223436
TI  - Insulin-like growth factor II and colorectal cancer risk in women.
AB  - Recently, a number of prospective studies showed evidence that the growth
      hormone/insulin-like growth factor I (IGF-I) axis may be important in the
      development of colorectal cancer. However, only a few studies have reported on
      the possible relationship of colorectal cancer risk with circulating levels of
      IGF-II, which are not growth hormone dependent and which do not vary with
      alterations in energy balance. In a case-control study of 102 cases and 200
      matched controls nested within a cohort of 14,275 women in New York, we examined
      the relationship between colorectal cancer risk and prediagnostic serum levels of
      IGF-II. Conditional logistic regression analysis showed an odds ratio (OR) for
      colorectal cancer of 2.02 (95% confidence interval (CI): 0.83-4.93), comparing
      the upper to lower quintile of IGF-II. This association was slightly attenuated
      after excluding IGF-II measurements in serum samples taken within 1 year before
      case diagnosis (OR of 1.81; 95% CI: 0.71-4.64) and moderately attenuated after
      excluding IGF-II measurements in serum samples taken within 2 years before case
      diagnosis (OR of 1.47; 95% CI: 0.56-3.91). Adjustment for IGF-1, IGF binding
      protein (BP)-1, IGFBP-3, smoking, or body mass index did not substantially alter
      the association, whereas adjustment for IGFBP-2 moderately attenuated the
      relationship. Our results confirm those of three recent case-control studies, and
      collectively these results suggest a possible increase in colorectal cancer risk
      among subjects with comparatively elevated serum IGF-II. Mechanisms that might
      cause the increase in IGF-II levels are unknown but may include loss of parental
      imprinting of the IGF-II gene.

PMID- 12223435
TI  - Multiple cancers associated with esophageal and oropharyngolaryngeal squamous
      cell carcinoma and the aldehyde dehydrogenase-2 genotype in male Japanese
      drinkers.
AB  - Aldehyde dehydrogenase-2 (ALDH2) is a key enzyme for the elimination of
      acetaldehyde, an established animal carcinogen generated by alcohol metabolism.
      In the presence of ALDH2*2, a mutant allele that is prevalent in East Asians,
      this enzyme is inactive, leading to excessive accumulation of acetaldehyde. Only
      among Japanese alcoholic patients has the positive association between this
      inactive form of ALDH2 and multiple-field cancerization in the upper
      aerodigestive tract been demonstrated. Whether this finding could be extended to
      multiple-cancer patients in general is of great interest, because the prevalence
      of esophageal cancer with other organ cancers has increased dramatically during
      recent decades in Japan. This study compared the ALDH2 genotypes of groups of
      male Japanese drinkers who had either esophageal squamous cell carcinomas (SCCs)
      with (n = 26) or without (n = 48) multiplicity or oropharyngolaryngeal SCCs with
      (n = 17) or without (n = 29) multiplicity. After adjustments for age and drinking
      and smoking habits, logistic regression analysis showed significantly increased
      risk for each multiplicity associated with either esophageal or
      oropharyngolaryngeal SCCs in the presence of the ALDH2*2 allele (odds ratio,
      5.26; 95% confidence interval, 1.08-51.06 and odds ratio, 7.36; 95% confidence
      interval, 1.29-80.70, respectively). This study is the first to strongly link
      inactive ALDH2 with the multiple cancer susceptibility of male Japanese drinkers
      with either esophageal or oropharyngolaryngeal cancers. A simple questionnaire
      about both current and past facial flushing after drinking a glass of beer was
      highly sensitive (95.6%) in detecting inactive ALDH2 in these patients and may be
      useful for identifying high-risk patients.

PMID- 12223437
TI  - Intake of supplemental and total fiber and risk of colorectal adenoma recurrence
      in the wheat bran fiber trial.
AB  - The Wheat Bran Fiber (WBF) trial was a double-blind Phase III clinical trial in
      which participants were randomized to a cereal fiber supplement of either 13.5 or
      2.0 g/day. No protective effect for adenoma recurrence was observed for those
      randomized to the high-fiber group as compared with those in the low-fiber group.
      However, the high-fiber group had significantly lower adherence to the supplement
      as assessed by cereal box counts. The aim of this study was to determine whether
      reported supplemental and total fiber intake affected colorectal adenoma
      recurrence in the WBF trial population, regardless of treatment group assignment.
      A total of 1208 participants who completed the WBF trial had a colonoscopy before
      the date of the last cereal box count and/or at least one colonoscopy within 90
      days after it and, thus, were eligible for the current analyses. Statistical
      analyses were done using multivariate logistic regression models that included
      potentially confounding variables. Compared with individuals consuming less than
      1.8 g/day of supplemental fiber, the adjusted odds ratio (95% confidence
      interval) for adenoma recurrence for those consuming greater than 11.0 g/day was
      0.94 (0.66-1.33). The odds ratio (95% confidence interval) for participants whose
      total fiber intake was greater than 30.3 g/day was 0.98 (0.68-1.42) compared with
      those whose intake was less than 17.9 g/day. The results of this study show that
      neither fiber intake from a wheat bran supplement nor total fiber intake affects
      the recurrence of colorectal adenomas, thus lending further evidence to the body
      of literature indicating that consumption of a high-fiber diet, especially one
      rich in cereal fiber, does not reduce the risk of colorectal adenoma recurrence.

PMID- 12223438
TI  - Effect of enzyme-resistant starch on formation of 1,N(2)-propanodeoxyguanosine
      adducts of trans-4-hydroxy-2-nonenal and cell proliferation in the colonic mucosa
      of healthy volunteers.
AB  - The effect of enzyme-resistant starch (RS) on the development of colon cancer was
      reported to include both chemopreventive activity in humans and tumorigenic
      activity in animals. A study was performed to detect the influence of enzyme-RS
      on lipid peroxidation-induced DNA damage and cell proliferation. During two 4
      week periods, 12 volunteers consumed a controlled diet in which starchy foods
      were enriched with a highly resistant amylomaize starch (Hylon VII) in the high
      RS period and with an available corn starch in the low-RS period (second period).
      At the end of each test period, biopsy specimens of the rectosigmoidal mucosa
      were obtained from each subject and analyzed for trans-4-hydroxy-2-nonenal-1,N(2)
      propanodeoxyguanosine-3'-monophosphate adducts using a (32)P postlabeling assay,
      and cell proliferation was determined by bromodeoxyuridine labeling. The trans-4
      hydroxy-2-nonenal-1,N(2)-propanodeoxyguanosine-3'-monophosphate adduct level of
      DNA from colonic mucosa of eight evaluated volunteers was significantly higher in
      the high-RS period (mean adducts/10(7) nucleotides +/- SD, 3.83 +/- 0.60) than in
      the low-RS period (2.69 +/- 0.35; P < 0.05). There was no evidence for an
      increased cell proliferation in the upper crypt in the high-RS phase, compared
      with the low-RS phase. There are indications now that enzyme-RS induces oxidative
      stress that is not correlated with increased cell proliferation. If it is
      accepted that the formation of DNA adducts reflects oxidative stress, which in
      turn accelerates the process of carcinogenesis, then certain forms of RS may have
      a tumor-enhancing effect rather than a tumor-protective effect.

PMID- 12223439
TI  - Risk of cancer among relatives of patients with glioma.
AB  - We report a population-based, retrospective study of 396 Icelandic people
      diagnosed with glioma in the years 1940-1995. The purpose of this study was to
      test whether astrocytomas, other glial tumors, other central nervous system
      tumors, or other cancers aggregate in families identified through glioma probands
      who were of Icelandic origin. Pedigrees of the 396 cases were traced by the
      Genetical Committee of the University of Iceland and linked to the Icelandic
      Cancer Registry. A total of 25,546 relatives, including 2,080 individuals with
      cancer were identified within these pedigrees. There was no statistically
      significant increase of glioma in relatives of glioma patients, nor was there any
      statistically significant increase in risk for other central nervous system
      tumors. There was no overall increase in incidence of all cancer combined, nor of
      specific common cancers (lung, prostate, breast, stomach, and colorectal) and
      uncommon cancers (melanoma and pancreas) in the relatives of glioma patients. Our
      results do not support the hypothesis of a familial aggregation of glioma
      indicative of a glioma susceptibility gene.

PMID- 12223440
TI  - Genotype analysis using human hair shaft.
AB  - Analysis of genotypes for genetic predisposition of diseases has profound and
      widespread clinical application and has become a fundamental tool in the study of
      molecular epidemiology. In this study, we report a convenient and completely
      noninvasive approach to perform genotyping using terminal cephalic hair shaft.
      The average and median DNA amounts purified from the hair shaft are 112 +/- 180
      (1 SD) pg/mg and 66 pg/mg of hair shaft, respectively. Using hybridization with
      molecular beacons that can reliably distinguish single nucleotide polymorphisms
      at different alleles, we are able to analyze the genotypes of APO-E and G-protein
      beta3 (GNB3) subunit C825T loci in DNA samples obtained from hair shaft in a high
      throughput format. The amount of DNA obtained from 20 mg of hair shaft is
      sufficient for multiple independent genotyping assays. These findings demonstrate
      that terminal hair shaft provides a convenient and reliable genomic DNA source
      for an analysis of genotypes.

PMID- 12223441
TI  - Differences in factors associated with oncogenic and nononcogenic human
      papillomavirus infection at the United States-Mexico border.
AB  - Previous studies have shown that risk factors for oncogenic (high-risk) and
      nononcogenic (low-risk) human papillomavirus (HPV) infection differ. To determine
      the risk factors for oncogenic and nononcogenic HPV infection in women residing
      along the United States-Mexico border, a cross-sectional study of type-specific
      HPV prevalence was conducted. Women (N=2246) ages 15-79 years, living in
      communities on both sides of the United States-Mexico border and attending family
      planning clinics were recruited. Women were screened for HPV and cytology and
      were asked to complete a health questionnaire. HPV status was determined by PCR,
      and HPV genotyping was performed using a reverse line blot hybridization assay
      (Roche Molecular Systems, Inc., Alameda, CA). Logistic regression analysis was
      conducted to determine factors independently associated with oncogenic and
      nononcogenic HPV infection in separate analyses. Similar to previous studies,
      lifetime number of sexual partners was only associated with oncogenic HPV
      infection. In contrast, nononcogenic HPV infection appeared to be associated with
      recent sexual activity, suggesting that nononcogenic infections may be more
      transient. Results from this study add to the growing literature suggesting that
      transmission and persistence of HPV differs by oncogenicity.

PMID- 12223442
TI  - Self-reported birth weight and subsequent risk of colorectal cancer.
AB  - Case series data suggest that high birth weight and neonatal macrosomia in
      offspring are associated with an increased risk of colorectal cancer in parents.
      We therefore conducted a prospective analysis investigating the association among
      self-reported birth weight, neonatal macrosomia, and incident colorectal cancer
      in a population-based study of men and women. Participants were drawn from a
      cohort of men and women ages between 45 and 79 years: the European Prospective
      Investigation of Cancer in Norfolk study. A total of 4532 men and 7325 women who
      reported their birth weight were followed up between 1993 and 1999. The relation
      between birth weight and incident colorectal cancer was assessed using Cox's
      proportional hazards model. All Ps are two-sided. The association between self
      reported birth weight and risk of incident colorectal cancer was nonlinear.
      Relative to individuals born weighing 2500-3249 g, the adjusted hazard ratio for
      people born with neonatal macrosomia was 2.57 (95% confidence interval = 1.15
      5.74). There was also some evidence that low birth weight babies were at
      increased risk of colorectal cancer relative to the referent category. These
      risks were essentially unaltered after adjustment for potential confounders.
      There is a J-shape relation between self-reported birth weight and subsequent
      risk of colorectal cancer. Babies born with macrosomia appear to have the
      greatest risk.

PMID- 12223443
TI  - DNA repair gene XRCC3 codon 241 polymorphism, its interaction with smoking and
      XRCC1 polymorphisms, and bladder cancer risk.
AB  - DNA repair efficiency varies among individuals, with reduced repair capacity as a
      risk factor for various cancers. This variability could be partly explained by
      allelic variants for different DNA repair genes. We examined the role of a common
      polymorphism in the XRCC3 gene (codon 241: threonine to methionine change) and
      bladder cancer risk. This gene plays a role in the homologous recombination
      pathway, which repairs double-strand breaks. The functional consequences of the
      XRCC3 codon 241 polymorphism are still unknown. We hypothesized that this
      polymorphism could affect repair of smoking-associated DNA damage and could
      thereby affect bladder cancer risk. We genotyped 233 bladder cancer cases and 209
      controls who had been frequency matched to cases on age, sex, and ethnicity. We
      observed little evidence of a positive association between subjects who carried
      at least one copy of the codon 241 Met allele and bladder cancer (odds ratio:
      1.3; 95% confidence interval: 0.9-1.9). Among heavy smokers, individuals with the
      Met allele had about twice the risk of those without it; however, a test of
      interaction was not statistically significant (P = 0.26). Previously, we observed
      in these subjects an association between bladder cancer risk and allelic variants
      of the XRCC1 gene, which is involved in the repair of base damage and single
      strand breaks. In this study, we found some evidence for a gene-gene interaction
      between the XRCC1 codon 194 and XRCC3 codon 241 polymorphisms (P = 0.09) and some
      support for a possible gene-gene-smoking three-way interaction (P = 0.08).

PMID- 12223444
TI  - A concerted, rational design of type 1 17beta-hydroxysteroid dehydrogenase
      inhibitors: estradiol-adenosine hybrids with high affinity.
AB  - Human estrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD type 1)
      catalyzes the final step in the synthesis of active estrogens that stimulate the
      proliferation of breast cancer cells. Based on the initial premise to make use of
      the binding energies of both the substrate and cofactor sites, and molecular
      modeling starting from the enzyme structure, several estradiol-adenosine hybrids
      were designed and synthesized. Among these hybrids, EM-1745 with a linker of 8
      CH2 groups is proved to be the best competitive inhibitor with a Ki of 3.0 +/-
      0.8 nM. The crystal structure of the EM-1745 enzyme complex at 1.6 A provides
      evidence at atomic resolution of strong interactions between both the steroid and
      cofactor moieties and the enzyme molecule, as illustrated by a deltaA-weighted
      2Fo-Fc electron density map contoured at 3.0 delta. The substrate entry loop is
      further stabilized in this complex compared with previous complexes of the
      enzyme. These results confirm our initial strategy of combining studies of
      structural biology and enzyme mechanism in the inhibitor design, which may be
      applied to other steroidogenic enzymes involved in human diseases.

PMID- 12223445
TI  - Alpha-synuclein regulates neuronal survival via Bcl-2 family expression and
      PI3/Akt kinase pathway.
AB  - Alpha-synuclein (alpha-SN) is a ubiquitous protein that is especially abundant in
      the brain and has been postulated to play a central role in the pathogenesis of
      Parkinson's disease, Alzheimer's disease, and other neurodegenerative disorders.
      However, little is known about the neuronal functions of alpha-SN and the
      molecular and cellular mechanisms underlying neuronal loss. Here, we show that
      alpha-SN plays dual roles of neuroprotection and neurotoxicity depending on its
      concentration or level of expression. At nanomolar concentrations, a-SN protected
      neurons against serum deprivation, oxidative stress, and excitotoxicity through
      the PI3/Akt signaling pathway, and its protective effect was increased by Bcl-2
      overexpression. Conversely, at both low micromolar and overexpressed levels in
      the cell, alpha-SN resulted in cytotoxicity. This might be related to decreased
      Bcl-xL expression and increased bax expression, which is subsequently followed by
      cytochrome c release and caspase activation and also by microglia-mediated
      inflammatory responses via the NFkappaB and mitogen-activated protein kinase
      pathways.

PMID- 12223446
TI  - Anti-monocyte chemoattractant protein-1 gene therapy inhibits restenotic changes
      (neointimal hyperplasia) after balloon injury in rats and monkeys.
AB  - Prevention of restenosis after coronary intervention is a major clinical
      challenge, which highlights the need of new therapeutic options. Vascular injury
      may involve inflammatory responses that accelerate the recruitment and activation
      of monocytes through the activation of chemotactic factors, including monocyte
      chemoattractant protein-1 (MCP-1). However, there is no definitive evidence
      supporting the role of MCP-1 in restenosis. We recently devised a new strategy
      for anti-MCP-1 gene therapy by transfecting an N-terminal deletion mutant of the
      MCP-1 gene into skeletal muscles. We demonstrate here that this strategy
      suppressed monocyte infiltration/activation in the injured site and markedly
      inhibited restenotic changes (neointimal hyperplasia) after balloon injury of the
      carotid artery in rats and monkeys. This strategy also suppressed the local
      production of MCP-1 and inflammatory cytokines. Therefore, monocyte infiltration
      and activation mediated by MCP-1 are essential in the development of restenotic
      changes after balloon injury. This strategy may be a useful form of gene therapy
      against human restenosis.

PMID- 12223448
TI  - The carboxyl-terminal activation domain of the STAT-1 transcription factor
      enhances ischemia/reperfusion-induced apoptosis in cardiac myocytes.
AB  - We have demonstrated previously that the STAT-1 transcription factor plays a key
      role in ischemia/reperfusion (I/R)-induced apoptosis in cardiac myocytes. In the
      present study we assessed which region of the STAT-1 molecule mediates apoptosis
      in cardiac myocytes. A STAT-1 construct (amino acid 350-750) lacking the N
      terminus could enhance I/R-induced apoptosis in cardiac myocytes. However, a STAT
      1 construct, which lacks 60 amino acids at the C-terminus (amino acid 691-750),
      was ineffective in promoting I/R-induced apoptosis in cardiac myocytes.
      Furthermore, overexpression of a C-terminal STAT-1 construct (amino acid 691-750)
      containing the transcriptional activation domain, but not the DNA binding domain,
      strongly enhanced I/R-induced apoptotic cell death. Cardiac myocytes isolated
      from mice expressing a truncated C-terminal STAT-1 were more sensitive to I/R
      induced cell death. Finally, isolated hearts from these animals exposed to I/R
      injury had larger infarct size and greater number of TUNEL-positive myocytes than
      control hearts. These studies demonstrate that the C-terminal transactivation
      domain of STAT-1 is necessary and sufficient for I/R injury-induced apoptosis in
      cardiac myocytes.

PMID- 12223447
TI  - Phosphatidylcholine synthesis is elevated in neuronal models of Gaucher disease
      due to direct activation of CTP:phosphocholine cytidylyltransferase by
      glucosylceramide.
AB  - Glucosylceramide (GlcCer) accumulates in the inherited metabolic disorder,
      Gaucher disease, because of the defective activity of lysosomal
      glucocerebrosidase. We previously demonstrated that upon GlcCer accumulation,
      cultured hippocampal neurons exhibit modified growth patterns, altered
      endoplasmic reticulum density, and altered calcium release from intracellular
      stores. We here examined the relationship between GlcCer accumulation and
      phospholipid synthesis. After treatment of neurons with an active site-directed
      inhibitor of glucocerebrosidase, or in neurons obtained from a mouse model of
      Gaucher disease, [14C]methyl choline incorporation into [14C]phosphatidylcholine
      ([14C]PC) and [14C]sphingomyelin was elevated, as were [14C]CDP-choline levels,
      suggesting that CTP:phosphocholine cytidylyltransferase (CCT) is activated.
      Indeed, CCT activity was elevated in neurons that had accumulated GlcCer. GlcCer,
      but not galactosylceramide (GalCer), stimulated CCT activity in rat brain
      homogenates, and significantly higher levels of CCT were membrane associated in
      cortical homogenates from a mouse model of Gaucher disease compared with wild
      type mice. Because CCT mRNA and protein levels were unaltered in either neurons
      or brain tissue that had accumulated GlcCer, it appeared likely that GlcCer
      activates CCT by a post-translational mechanism. This was verified by examination
      of the effect of GlcCer on CCT purified about 1200-fold from rat brain. GlcCer
      stimulated CCT activity, with stimulation observed at levels as low as 2.5 mol%
      and with maximal activation reached at 10 mol%. In contrast, GalCer had no
      effect. Together, these data demonstrate that GlcCer directly activates CCT,
      which results in elevated PC synthesis, which may account for some of the changes
      in growth rates observed upon neuronal GlcCer accumulation.

PMID- 12223449
TI  - Inhibition of erythropoietin gene expression signaling involves the transcription
      factors GATA-2 and NF-kappaB.
AB  - The anemia of chronic inflammatory and malignant diseases is partly due to
      impaired synthesis of the hormone erythropoietin (Epo). The proinflammatory
      cytokines interleukin-1 (IL-1) and tumor necrosis factor a (TNF-alpha) suppress
      in vitro Epo gene expression and Epo protein secretion. However, the molecular
      mechanisms of this inhibition are poorly understood. The human Epo promoter and
      the 5' flanking region contain several recognition sequences for transcription
      factors acting either positively or negatively. Herein, we investigated the roles
      of the transcription factors GATA-2 and NF-kappaB in the modulation of Epo gene
      expression by IL-1beta and TNF-alpha in the human hepatoma cell line HepG2.
      Electrophoretic mobility shift assays revealed increased GATA-2 and NF-kappaB DNA
      binding in cells treated with IL-1beta or TNF-alpha. Reporter gene assays with a
      sequence from the Epo promoter in front of the firefly luciferase gene showed
      that the cytokines reduced Epo reporter gene activity. Functional inactivation of
      GATA-2 and NF-kappaB by oligo-decoy techniques prevented the inhibition of Epo
      production by IL-1beta and TNF-alpha. In HepG2 cells stably transfected with a
      dominant-negative form of IkappaBalpha, the activation of NF-kappaB was
      inhibited, while Epo mRNA levels and Epo secretion increased. Thus, both GATA-2
      and NF-kappaB seem to be involved in the suppression of Epo gene expression by IL
      1beta and TNF-alpha in vitro and may be responsible for impaired Epo synthesis in
      inflammatory diseases in vivo.

PMID- 12223450
TI  - Critical role of NF-kappaB and stress-activated protein kinases in steroid
      unresponsiveness.
AB  - Glucocorticoid resistance is a serious clinical problem in chronic inflammatory
      diseases, because many patients with rheumatoid arthritis, asthma, or Crohn's
      disease fail to respond to steroid treatment. The molecular mechanisms underlying
      this unresponsiveness, however, are completely unknown. The effects of steroids
      are largely mediated by the interference of the glucocorticoid receptor (GR) with
      proinflammatory transcription factors. In the present study, we therefore
      investigated the activation of the transcription factors nuclear factor-kappaB
      (NF-kappaB), activator protein-1 (AP-1), and the upstream kinases p38 and c-Jun N
      terminal kinase (JNK) in steroid-sensitive and steroid-resistant patients with
      Crohn's disease. We demonstrated that steroid-sensitive and steroid-resistant
      patients reveal a remarkably different cellular activation pattern of these
      proinflammatory mediators. In steroid-sensitive patients, activation of NF
      kappaB, AP-1, p38, and JNK was mainly found in lamina propria macrophages. In
      contrast, steroid-resistant patients revealed activation of all these mediators
      mostly in epithelial cells. The functional interference of the proinflammatory
      mediators with the glucocorticoid response was supported by reporter gene assays.
      Expression of NF-kappaB and, interestingly, also JNK1 and p38 inhibited the
      activity of the GR. Thus, our results suggest that steroid resistance is
      associated with increased epithelial activation of stress-activated protein
      kinases and NF-kappaB, which might inhibit the anti-inflammatory action of a
      limited number of GRs.

PMID- 12223451
TI  - Vasoactive intestinal peptide and pituitary adenylate cyclase-activating
      polypeptide promote in vivo generation of memory Th2 cells.
AB  - Functionally active effector T cells are generated through clonal expansion. Most
      effector T cells are later eliminated, whereas a small number survive and
      differentiate into memory T cells. The mechanisms by which some effector T cells
      escape apoptosis and become memory T cells are not understood. Neuropeptides such
      as the vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase
      activating polypeptide (PACAP) inhibit antigen-induced apoptosis of CD4 T cells.
      By using an in vivo long-term experimental model, in which CD4 T cells from TRC
      transgenic mice were transferred into hosts, we demonstrate that VIP and PACAP
      induce the survival and/or generation of antigen-specific CD4 T cells with a
      memory Th2 phenotype. This was confirmed by the fact that transgenic CD4 T cells
      were recovered only from mice that received Th2, but not Th1 effector cells, in
      the presence of VIP or PACAP. In vitro, VIP/PACAP support the survival of Th2,
      but not Th1, cell lines through an inhibition of antigen-induced apoptosis. The
      role of neuropeptides in the biased development of Th2 memory cells is
      particularly relevant in view of the immune deviation existing in immune
      privileged sites such as the brain and eye, where Th2, but not Th1, responses
      occur in nonpathological conditions.

PMID- 12223453
TI  - Cell culture on thin tissue sections commonly prepared for histopathology.
AB  - Thin tissue sections commonly prepared on a glass slide for histopathology retain
      many in vivo biochemical attributes related not only to structure but also
      function. We hypothesized that such tissue sections might serve as novel cell
      culture substrata that would reflect tissue conditions in vivo. Here we report
      the applicability of tissue section substrata to tissue reconstruction and serum
      free culture. Four different cell types were cultured on section and
      acellularized section substrata prepared from a bovine placenta. The labyrinth
      region of the substratum induced cell differentiation to elicit the formation of
      multicellular spheroids of BeWo cells (human choriocarcinoma cells), a capillary
      network-like structure for CPAE cells (bovine pulmonary artery endothelial
      cells), and a neuronal network-like structure for PC-12 cells (rat
      pheochromocytoma cells). The substratum provided a microenvironment that
      maintained the viability of PC-12 cells in a serum-free culture. We also
      succeeded in preparing a multicellular mass of normal human dermal fibroblasts
      (NHDFs) involving acellularized section-derived components. This technology
      offers the novel investigation of cell behaviors induced by culturing different
      cell types on various tissue sections and will be a useful tool for identifying
      cell characteristics and clarifying the molecular mechanisms that regulate the
      behavior of each cell type.

PMID- 12223452
TI  - 1alpha,25-dihydroxyvitamin D3 inhibits uncoupling protein 2 expression in human
      adipocytes.
AB  - We recently demonstrated that suppressing 1alpha,25-(OH)2-D3 by increasing
      dietary calcium decreases adipocyte intracellular Ca2+ ([Ca2+]i), stimulates
      lipolysis, and inhibits lipogenesis. High calcium diets also increase core
      temperature and white adipose tissue uncoupling protein 2 (UCP2) expression in
      aP2-agouti transgenic mice. Accordingly, we have evaluated the role of 1alpha,25
      (OH)2-D3 in regulating human adipocyte UCP2 expression. Treatment of human
      adipocytes for 48 h with 1 nM 1alpha,25-(OH)2-D3 inhibited UCP2 mRNA and protein
      levels by 50% (P<0.002) and completely blocked isoproterenol- or fatty acid
      stimulated two- to threefold increases in UCP2 expression. However, a specific
      agonist for the membrane vitamin D receptor (mVDR), 1alpha,25
      dihydroxylumisterol3, was unable to inhibit basal, isoproterenol-stimulated, or
      fatty acid-stimulated UCP2 expression, whereas a specific mVDR
      antagonist,1beta,25-dihydroxyvitamin D3, was unable to prevent the 1alpha,25
      (OH)2-D3 inhibition of UCP2 expression. In contrast, nuclear vitamin D receptor
      (nVDR) knockout via antisense oligodeoxynucleotide (ODN) prevented the inhibitory
      effect of 1alpha,25-(OH)2-D3 on adipocyte UCP2 expression and protein levels.
      These data indicate that 1a,25-(OH)2-D3 exerts an inhibitory effect on adipocyte
      UCP2 expression via the nVDR. Thus, suppression of 1alpha,25-(OH)2-D3 and
      consequent up-regulation of UCP2 may contribute to our previous observation of
      increased thermogenesis in mice fed with high calcium diets.

PMID- 12223455
TI  - Learning from ENRON.

PMID- 12223454
TI  - Lipoxin, leukotriene, and PDGF receptors cross-talk to regulate mesangial cell
      proliferation.
AB  - The lipoxygenase-derived leukotrienes (LTs) are important proinflammatory lipid
      mediators. Lipoxins (LXs), more recently described lipoxygenase products,
      modulate many proinflammatory actions of LTs and have impressive proresolution
      properties. Mesangial cell (MC) proliferation is a central event in the
      pathogenesis of glomerulonephritis. LTD4-induced proliferation of mesangial cells
      is modulated by LXA4. Here, we demonstrate that LXA4 inhibits PDGF- and LTD4
      stimulated proliferation through modulation of platelet-derived growth factor
      receptor beta (PDGFRbeta) activation. Specifically, we demonstrate that LTD4
      transactivates the PDGFRbeta, a process associated with c-src recruitment and ras
      activation. We demonstrate expression of cysLT1 and cysLT2 receptors in MCs. LTD4
      induced c-src activation was insensitive to pertussis toxin and the cysLT1
      receptor antagonist Zafirlukast but was blocked by the nonselective antagonist
      Pobilukast. We show that LXA4 inhibits LTD4-stimulated activation of the
      PDGFRbeta and that LXA4 modulates PDGF-BB-stimulated tyrosine phosphorylation of
      the PDGFRb and subsequent mitogenic events. Furthermore, expression of
      recombinant LXA4 receptor (ALXR) in CHOK1 cells was associated with an
      attenuation of serum-stimulated proliferation. These data demonstrate that LXA4
      receptor (ALXR) activation is accompanied by antimitogenic effects coupled with
      inactivation of growth factor receptors, highlighting the complex cross-talk
      between G protein-coupled receptors and receptor tyrosine kinases in an
      inflammatory milieu. These data elaborate on the profile of cell signaling events
      that underpin the anti-inflammatory and proresolution bioactions of LX.

PMID- 12223456
TI  - Cures for the Third World's problems: the application of genomics to the diseases
      plaguing the developing world may have huge medical and economic benefits for
      those countries and might even prevent armed conflict.

PMID- 12223457
TI  - Rhythm 'n' biology: what happens if cell biology and techno music meet?

PMID- 12223458
TI  - Asian pragmatism: Japan has set up a legal framework to allow the use and
      generation of human embryonic stem cell lines.

PMID- 12223459
TI  - Science on the stage: recent plays on scientific topics show that science and
      theatre have more in common than it appears.

PMID- 12223462
TI  - Keeping up with calcium: conference on calcium-binding proteins and calcium
      function in health and disease.

PMID- 12223463
TI  - Navigating the secretory pathway: conference on exocytosis membrane structure and
      dynamics.

PMID- 12223464
TI  - The ins and outs of APC and beta-catenin nuclear transport.
AB  - Adenomatous polyposis coli (APC) and beta-catenin, two key interacting proteins
      implicated in development and cancer, were recently found to traffic into and out
      of the nucleus in response to internal and external signals. The two proteins can
      enter and exit the nucleus independently, a discovery that has prompted debate
      about the previously proposed role of APC as a beta-catenin chaperone. Here, we
      review the regulation of APC and beta-catenin subcellular localization, in
      particular in cancer cells. We speculate that, in non-stimulated cells, APC
      actively exports beta-catenin from the nucleus to the cytoplasm where its levels
      are regulated by degradation; and, conversely, that, in cancer cells or those
      stimulated by Wnt signaling, beta-catenin degradation is inhibited and the
      accruing protein is capable of moving between the nucleus and cytoplasm
      independently of APC. Models that link APC and beta-catenin transport to function
      are discussed.

PMID- 12223466
TI  - Plant architecture.
AB  - Plant architecture is species specific, indicating that it is under strict
      genetic control. Although it is also influenced by environmental conditions such
      as light, temperature, humidity and nutrient status, here we wish to focus only
      on the endogenous regulatory principles that control plant architecture. We
      summarise recent progress in the understanding of the basic patterning mechanisms
      involved in the regulation of leaf arrangement, the genetic regulation of
      meristem determinacy, i.e. the decision to stop or continue growth, and the
      control of branching during vegetative and generative development. Finally, we
      discuss the basis of leaf architecture and the role of cell division and cell
      growth in morphogenesis.

PMID- 12223465
TI  - Keeping a good pathway down: transcriptional repression of Notch pathway target
      genes by CSL proteins.
AB  - CSL [CBF-1, Su(H), Lag-1]-type transcription factors are the primary effectors of
      the Notch pathway, a signal transduction cascade that is essential for the
      development of all metazoan organisms. Interestingly, CSL proteins were
      originally classified as transcriptional repressors in vertebrates, but as
      transcriptional activators in model invertebrate organisms. Resolution of this
      paradox came with the realization that repression and activation by CSL proteins
      occurs in both systems and that the switch involves recruitment of distinct co
      repressor and co-activator complexes. Although CSL proteins appear to utilize a
      common co-activator complex of largely similar constitution, recent studies have
      demonstrated that vertebrate and Drosophila CSL interact with a variety of
      distinct co-repressor complexes. This review highlights differences in
      composition and similarities in function of different CSL co-repressor complexes,
      which actively repress Notch pathway target genes in the absence of Notch pathway
      activity.

PMID- 12223467
TI  - The N termini of focal adhesion kinase family members regulate substrate
      phosphorylation, localization, and cell morphology.
AB  - The focal adhesion kinase (FAK) and cell adhesion kinase beta (CAKbeta, PYK2,
      CADTK, RAFTK) are highly homologous FAK family members, yet clearly have unique
      roles in the cell. Comparative analyses of FAK and CAKbeta have revealed
      intriguing differences in their activities. These differences were investigated
      further through the characterization of a set of FAK/CAKbeta chimeric kinases.
      CAKbeta exhibited greater catalytic activity than FAK in vitro, providing a
      molecular basis for differential substrate phosphorylation by FAK and CAKbeta in
      vivo. Furthermore, the N terminus may regulate catalytic activity since chimeras
      containing the FAK N terminus and CAKbeta catalytic domain exhibited a striking
      high level of catalytic activity and substrate phosphorylation. Unexpectedly, a
      modulatory role for the N termini in subcellular localization was also revealed.
      Chimeras containing the FAK N terminus and CAKbeta C terminus localized to focal
      adhesions, whereas chimeras containing the N and C termini of CAKbeta did not.
      Finally, prominent changes in cell morphology were induced upon expression of
      chimeras containing the CAKbeta N terminus, which were not associated with
      apoptotic cell death, cell cycle progression delay, or changes in Rho activity.
      These results demonstrate novel regulatory roles for the N terminus of FAK family
      kinases.

PMID- 12223468
TI  - Purification and properties of a phospholipase A2/lipase preferring phosphatidic
      acid, bis(monoacylglycerol) phosphate, and monoacylglycerol from rat testis.
AB  - Phospholipase A(2) (PLA(2)) was purified to homogeneity from the supernatant
      fraction of rat testis homogenate. The purified 63-kDa enzyme did not require
      Ca(2+) ions for activity and exhibited both phosphatidic acid-preferring PLA(2)
      and monoacylglycerol lipase activities with a modest specificity toward
      unsaturated acyl chains. Anionic detergents enhanced these activities. Serine
      modifying irreversible inhibitors, (p-amidinophenyl) methanesulfonyl fluoride and
      methylarachidonyl fluorophosphonate, inhibited both activities to a similar
      extent, indicating a single active site is involved in PLA(2) and lipase
      activities. The sequence of NH(2)-terminal 12 amino acids of purified enzyme was
      identical to that of a carboxylesterase from rat liver. The optimal pH for PLA(2)
      activity (around 5.5) differed from that for lipase activity (around 8.0). At pH
      5.5 the enzyme also hydrolyzed bis(monoacylglycerol) phosphate, or
      lysobisphosphatidic acid (LBPA), that has been hitherto known as a secretory
      PLA(2)-resistant phospholipid and a late endosome marker. LBPA-enriched fractions
      were prepared from liver lysosome fractions of chloroquine-treated rats, treated
      with excess of pancreatic PLA(2), and then used for assaying LBPA-hydrolyzing
      activity. LBPA and the reaction products were identified by microbore normal
      phase high performance liquid chromatography/electrospray ionization ion-trap
      mass spectrometry. These enzymatic properties suggest that the enzyme can
      metabolize phosphatidic and lysobisphosphatidic acids in cellular acidic
      compartments.

PMID- 12223469
TI  - EphB1 associates with Grb7 and regulates cell migration.
AB  - EphB1 is a member of the Eph family of receptor tyrosine kinases that play
      important roles in diverse biological processes including nervous system
      development, angiogenesis, and neural synapsis formation and maturation. Grb7 is
      an adaptor molecule implicated in the regulation of cell migration. Here we
      report identification of an interaction between Grb7 and the cytoplasmic domain
      of EphB1 by using Grb7 as a "bait" in a yeast two-hybrid screening. Co
      immunoprecipitation was used to confirm the interaction of Grb7 with the
      cytoplasmic domain of EphB1 as well as the full-length receptor in intact cells.
      This interaction is mediated by the SH2 domain of Grb7 and requires tyrosine
      autophosphorylation of EphB1. Furthermore, Tyr-928 of EphB1 was identified as the
      primary binding site for Grb7. Stimulation of endogenous EphB1 in embryonal
      carcinoma P19 cells with its ligand ephrinB1 increased its association with Grb7,
      which is consistent with a role for the autophosphorylation of EphB1. We also
      found that EphB1 could phosphorylate Grb7 and mutation of either Tyr-928 or Tyr
      594 to Phe decreased this activity. Finally, we show that EphB1 could stimulate
      fibroblast motility on extracellular matrix in a kinase-dependent manner, which
      also correlated with its association with Grb7. Consistent with this, co
      expression of Grb7 with EphB1 further enhanced cell motility, whereas co
      expression of the Grb7 SH2 domain abolished EphB1-stimulated cell migration.
      Together, our results identified a novel interaction between EphB1 with the
      adaptor molecule Grb7 and suggested that this interaction may play a role in the
      regulation of cell migration by EphB1.

PMID- 12223470
TI  - Solubilization of receptors for the novel Ca2+-mobilizing messenger, nicotinic
      acid adenine dinucleotide phosphate.
AB  - Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca(2+)
      mobilizing agent in a variety of broken and intact cell preparations. In sea
      urchin egg homogenates, NAADP releases Ca(2+) independently of inositol
      trisphosphate or ryanodine receptor activation. Little, however, is known
      concerning the molecular target for NAADP. Here we report for the first time
      solubilization of NAADP receptors from sea urchin egg homogenates. Supernatant
      fractions, prepared following Triton X-100 treatment, bound [(32)P]NAADP with
      similar affinity and selectivity as membrane preparations. Furthermore, the
      unusual non-dissociating nature of NAADP binding to its receptor was preserved
      upon solubilization. NAADP receptors could also be released into supernatant
      fractions upon detergent treatment of membranes prelabeled with [(32)P]NAADP.
      Tagged receptors prepared in this way, were readily resolved by native gel
      electrophoresis as a single protein target. Gel filtration and sucrose density
      gradient centrifugation analysis indicates that NAADP receptors are substantially
      smaller than inositol trisphosphate or ryanodine receptors, providing further
      biochemical evidence that NAADP activates a novel intracellular Ca(2+) release
      channel.

PMID- 12223471
TI  - Linker histone subtype composition and affinity for chromatin in situ in
      nucleated mature erythrocytes.
AB  - The replacement linker histones H1(0) and H5 are present in frog and chicken
      erythrocytes, respectively, and their accumulation coincides with cessation of
      proliferation and compaction of chromatin. These cells have been analyzed for the
      affinity of linker histones for chromatin with cytochemical and biochemical
      methods. Our results show a stronger association between linker histones and
      chromatin in chicken erythrocyte nuclei than in frog erythrocyte nuclei. Analyses
      of linker histones from chicken erythrocytes using capillary electrophoresis
      showed H5 to be the subtype strongest associated with chromatin. The
      corresponding analyses of frog erythrocyte linker histones using reverse-phase
      high performance liquid chromatography showed that H1(0) dissociated from
      chromatin at somewhat higher ionic strength than the three additional subtypes
      present in frog blood but at lower ionic strength than chicken H5. Which of the
      two H1(0) variants in frog is expressed in erythrocytes has thus far been
      unknown. Amino acid sequencing showed that H1(0)-2 is the only H1(0) subtype
      present in frog erythrocytes and that it is 100% acetylated at its N termini. In
      conclusion, our results show differences between frog and chicken linker histone
      affinity for chromatin probably caused by the specific subtype composition
      present in each cell type. Our data also indicate a lack of correlation between
      linker histone affinity and chromatin condensation.

PMID- 12223472
TI  - Mechanisms of conversion of plasminogen activator inhibitor 1 from a suicide
      inhibitor to a substrate by monoclonal antibodies.
AB  - We have delineated two different reaction mechanisms of monoclonal antibodies
      (mAbs), MA-8H9D4 and either MA-55F4C12 or MA-33H1F7, that convert plasminogen
      activator inhibitor 1 (PAI-1) to a substrate for tissue (tPA)- and urokinase
      plasminogen activators. MA-8H9D4 almost completely (98-99%) shifts the reaction
      to the substrate pathway by preventing disordering of the proteinase active site.
      MA-8H9D4 does not affect the rate-limiting constants (k(lim)) for the insertion
      of the reactive center loop cleaved by tPA (3.5 s(-1)) but decreases k(lim) for
      urokinase plasminogen activator from 25 to 4.0 s(-1). MA-8H9D4 does not cause
      deacylation of preformed PAI-1/proteinase complexes and probably acts prior to
      the formation of the final inhibitory complex, interfering with displacement of
      the acylated serine from the proteinase active site. MA-55F4C12 and MA-33H1F7 (50
      80% substrate reaction) do not interfere with initial PAI-1/proteinase complex
      formation but retard the inhibitory pathway by decreasing k(lim) (>10-fold for
      tPA). Interaction of two mAbs with the same molecule of PAI-1 has been directly
      demonstrated for pairs MA-8H9D4/MA-55F4C12 and MA-8H9D4/MA-33H1F7 but not for MA
      55F4C12/MA-33H1F7. The strong functional additivity observed for MA-8H9D4 and MA
      55F4C12 demonstrates that these mAbs interact independently and affect different
      steps of the PAI-1 reaction mechanism.

PMID- 12223473
TI  - HSos1 contains a new amino-terminal regulatory motif with specific binding
      affinity for its pleckstrin homology domain.
AB  - The protein hSos1 is a Ras guanine nucleotide exchange factor. In the present
      study, we investigated the function of the amino-terminal region of the hSos1
      protein, corresponding to the first 600 residues, which includes the Dbl and
      pleckstrin homology (DH and PH) domains. We demonstrated, using a series of
      truncated mutants, that this region is absolutely necessary for hSos1 activity.
      Our results suggest that the first 200 residues (upstream of DH domain), which we
      called the HF motif on the basis of their homology with histone H2A, may exert
      negative control over the functional activity of the whole hSos1 protein. In
      vitro binding analysis showed that the HF motif is able to interact specifically
      with the PH domain of hSos1. The amino-terminal region of hSos1 may be associated
      in vivo with an expressed HF motif. These findings document the existence of the
      HF motif located upstream of the DH domain in the hSos1 protein. This motif may
      be responsible for the negative control of hSos1, probably by intramolecular
      binding with the PH domain.

PMID- 12223475
TI  - Rapid activation of glycogen phosphorylase by the endoplasmic reticulum unfolded
      protein response.
AB  - Endoplasmic reticulum (ER) stress is associated with misfolding of ER proteins
      and triggers the unfolded protein response (UPR). The UPR, in turn, helps restore
      normal ER function. Since fastidious N-linked glycosylation is critical for
      folding of most ER proteins, this study examined whether metabolic
      interconversions of precursors used for glycan assembly were controlled by the
      UPR. Thus, eight enzymes and factors with key roles in hexose phosphate
      metabolism were assayed in cytoplasmic extracts from primary dermal fibroblasts
      treated with UPR inducers. Stimulation of only one activity by the UPR was
      detected, AMP-independent glycogen phosphorylase (GP). GP activation required
      only 20 min of ER stress, with concurrent decreases in cellular glycogen and
      elevations of its metabolites Glc-1-P and Glc-6-P. Addition of phosphatase
      inhibitors to enzyme extracts from unstressed cells mimicked the effect of ER
      stress on GP activity, suggesting that phosphorylation of GP or a regulatory
      factor was involved. These data show that the UPR can modulate hexose metabolism
      in a manner beneficial for protein glycosylation. Since activation of GP appears
      to occur by a rapid post-translational process, it may be part of a general
      strategy of ER damage control, preceding the well-known transcription-dependent
      processes of the UPR that are manifested hours after the occurrence of ER stress.

PMID- 12223474
TI  - Mechanism of regulation of casein kinase I activity by group I metabotropic
      glutamate receptors.
AB  - Previously, we reported that (S)-3,5-dihydroxypenylglycine (DHPG), an agonist for
      group I metabotropic glutamate receptors (mGluRs), stimulates CK1 and Cdk5 kinase
      activities in neostriatal neurons, leading to enhanced phosphorylation,
      respectively, of Ser-137 and Thr-75 of DARPP-32 (dopamine and cAMP-regulated
      phosphoprotein, 32 kDa). We have now investigated the signaling pathway that
      leads from mGluRs to casein kinase 1 (CK1) activation. In mouse neostriatal
      slices, the effect of DHPG on phosphorylation of Ser-137 or Thr-75 of DARPP-32
      was blocked by the phospholipase Cbeta inhibitor, the Ca(2+) chelator 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA/AM), and the calcineurin
      inhibitor cyclosporin A. In neuroblastoma N2a cells, the effect of DHPG on the
      activity of transfected HA-tagged CK1(epsilon) was blocked by BAPTA/AM and
      cyclosporin A. In neostriatal slices, the effect of DHPG on Cdk5 activity was
      also abolished by BAPTA/AM and cyclosporin A, presumably through blocking
      activation of CK1. Metabolic labeling studies and phosphopeptide mapping revealed
      that a set of C-terminal sites in HA-CK1epsilon were transiently dephosphorylated
      in N2a cells upon treatment with DHPG, and this was blocked by cyclosporin A. A
      mutant CK1epsilon with a nonphosphorylatable C-terminal domain was not activated
      by DHPG. Together, these studies suggest that DHPG activates CK1(epsilon) via
      Ca(2+)-dependent stimulation of calcineurin and subsequent dephosphorylation of
      inhibitory C-terminal autophosphorylation sites.

PMID- 12223477
TI  - Protein kinase C(mu) regulation of the JNK pathway is triggered via
      phosphoinositide-dependent kinase 1 and protein kinase C(epsilon).
AB  - The protein kinase C (PKC)-related enzyme PKC(mu)/PKD (protein kinase D) is
      activated by activation loop phosphorylation through PKC(eta). Here we
      demonstrate that PKC(mu) is activated by the direct phosphorylation of
      PKC(epsilon). PKC(mu) colocalizes with PKC(epsilon) in HEK293 and MCF7 cells as
      shown by confocal immunofluorescence analyses. PDK1, known as the upstream kinase
      for several PKC isozymes, associates intracellularly with PKC(epsilon) and
      PKC(eta). PKC(eta) is phosphorylated by PDK1 in vitro, leading to kinase
      activation as similarly reported for PKC(epsilon) activation by PDK1.
      Coexpression of PDK1, PKC(epsilon) and PKC(mu) in HEK293 cells results in PKC(mu)
      activation. In contrast, the coexpression of PDK1 and PKC(eta) with PKC(mu) does
      not activate PKC(eta) or consequently PKC(mu). PDK1/PKC(epsilon)-triggered
      activation of PKC(mu) inhibits JNK, a downstream effector of PKC(mu), whereas
      upon transient expression of PDK1, PKC(eta), and PKC(mu), JNK is not affected.
      These data implicate PKC(epsilon) as the biologically important upstream kinase
      for PKC(mu) in HEK293 cells, regulating downstream effectors. Our results further
      indicate a PDK1/PKC(eta)/PKC(mu) controlled negative regulation of PKC(eta)
      kinase activity. In this study, we show that differentially activated kinase
      cascades involving PDK1 and novel PKC isotypes are responsible for the regulation
      of PKC(mu) activity and consequently inhibit the JNK pathway.

PMID- 12223476
TI  - Suppression of cholesterol 7alpha-hydroxylase transcription and bile acid
      synthesis by an alpha1-antitrypsin peptide via interaction with alpha1
      fetoprotein transcription factor.
AB  - alpha1-Antitrypsin (alpha1-AT) is a serum protease inhibitor that is synthesized
      mainly in the liver, and its rate of synthesis markedly increases in response to
      inflammation. This increase in alpha1-AT synthesis results in an increase in
      peptides, like its carboxyl-terminal C-36 peptide (C-36), resulting from alpha1
      AT cleavage by proteases. Atherosclerosis is a form of chronic inflammation, and
      one of the risk factors is elevated plasma cholesterol levels. Because of the
      correlation between atherosclerosis, plasma cholesterol content, inflammation,
      and alpha1-AT rate of synthesis, we investigated the effect of the C-36 serpin
      peptide on hepatic bile acid biosynthesis. We discovered that C-36 is a powerful
      and specific transcriptional down-regulator of bile acid synthesis in primary rat
      hepatocytes, through inhibition of the cholesterol 7alpha-hydroxylase/CYP7A1
      (7alpha-hydroxylase) promoter. Mice injected with the C-36 peptide also showed a
      decrease in 7alpha-hydroxylase mRNA. A mutated but very similar peptide did not
      have any effect on 7alpha-hydroxylase mRNA or its promoter. The sterol 12alpha
      hydroxylase/CYP8B1 (12alpha-hydroxylase) promoter is also down-regulated by the C
      36 peptide in HepG2 cells but not by the mutated peptide. The DNA element
      involved in the C-36-mediated regulation of 7alpha- and 12alpha-hydroxylase
      promoters mapped to the alpha1-fetoprotein transcription factor (FTF) site in
      both promoters. The C-36 peptide prevented binding of FTF to its target DNA
      recognition site by direct interaction with FTF. We hypothesize that the C-36
      peptide specifically interacts with FTF and induces a conformational change that
      results in loss of its DNA binding ability, which results in suppression of
      7alpha- and 12alpha-hydroxylase transcription. These results suggest that
      peptides derived from specific serum proteins may alter hepatic gene expression
      in a highly specific manner.

PMID- 12223478
TI  - Mutations within an intramembrane leucine heptad repeat disrupt oligomer
      formation of the rat GABA transporter 1.
AB  - Na(+)/Cl(-)-dependent neurotransmitter transporters form constitutive oligomers,
      the significance of which is not known. In soluble proteins, leucine heptad
      repeats drive dimerization; the rat gamma-aminobutyric acid transporter GAT-1
      (rGAT) contains a motif reminiscent of a leucine heptad repeat in the second
      transmembrane helix (TM2). We substituted leucine residues in TM2 of rGAT by
      alanine and tested the ability of the resulting mutants to form oligomers by
      three methods of Forster resonance energy transfer (FRET) microscopy. Replacement
      of one leucine (L97A) resulted in considerable loss of energy transfer, replacing
      two or more ablated it completely. Furthermore, intracellular trapping increased
      with the number of leucine substitutions. Only rGAT-L97A reached the cell surface
      to a sufficient amount such that, in intact cells, it was indistinguishable from
      wild type rGAT with respect to substrate transport, binding of inhibitors, and
      regulation by protein kinase C. However, in membrane vesicles prepared from
      transfected cells, all mutants were still functional. In addition, FRET was
      readily detected during maturation of wild type rGAT, when the bulk of the
      protein resided in the endoplasmic reticulum. Hence, our findings strongly argue
      for a role of oligomer formation during biosynthesis and subsequent delivery of
      the multimer from the endoplasmic reticulum to the plasma membrane.

PMID- 12223479
TI  - Reciprocal modulation between the alpha and beta 4 subunits of hSlo calcium
      dependent potassium channels.
AB  - Large conductance Ca(2+)-dependent potassium (K(Ca) or maxi K) channels are
      composed of a pore-forming alpha subunit and an auxiliary beta subunit. We have
      shown that the brain-specific beta4 subunit modulates the voltage dependence,
      activation kinetics, and toxin sensitivity of the hSlo channel (Weiger, T. M.,
      Holmqvist, M. H., Levitan, I. B., Clark, F. T., Sprague, S., Huang, W. J., Ge,
      P., Wang, C., Lawson, D., Jurman, M. E., Glucksmann, M. A., Silos-Santiago, I.,
      DiStefano, P. S., and Curtis, R. (2000) J. Neurosci. 20, 3563-3570). We
      investigated here the N-linked glycosylation of the beta4 subunit and its effect
      on the modulation of the hSlo alpha subunit. When expressed alone in HEK293
      cells, the beta4 subunit runs as a single molecular weight band on an SDS gel.
      However, when coexpressed with the hSlo alpha subunit, the beta4 subunit appears
      as two different molecular weight bands. Enzymatic deglycosylation or mutation of
      the N-linked glycosylation residues in beta4 converts it to a single lower
      molecular weight band, even in the presence of the hSlo alpha subunit, suggesting
      that the beta4 subunit can be present as an immature, core glycosylated form and
      a mature, highly glycosylated form. Blockage of protein transport from the
      endoplasmic reticulum to the Golgi compartment with brefeldin A abolishes the
      mature, highly glycosylated beta4 band. Glycosylation of the beta4 subunit is not
      required for its binding to the hSlo channel alpha subunit. It also is not
      necessary for cell membrane targeting of the beta4 subunit, as demonstrated by
      surface biotinylation experiments. However, the double glycosylation site mutant
      beta4 (beta4 N53A/N90A) protects the channel less against toxin blockade, as
      compared with the hSlo channel coexpressed with wild type beta4 subunit. Taken
      together, these data show that the pore-forming alpha subunit of the hSlo channel
      promotes N-linked glycosylation of its auxiliary beta4 subunit, and this in turn
      influences the modulation of the channel by the beta4 subunit.

PMID- 12223480
TI  - Characterization of mammalian stanniocalcin receptors. Mitochondrial targeting of
      ligand and receptor for regulation of cellular metabolism.
AB  - The polypeptide hormone stanniocalcin (STC) is widely expressed in mammalian
      tissues. STC acts locally in kidney and gut to modulate calcium and phosphate
      excretion, and its overexpression in mice results in high serum phosphate,
      dwarfism, and increased metabolic rate. STC has also been linked to cancer,
      pregnancy, lactation, angiogenesis, organogenesis, cerebral ischemia, and
      hypertonic stress. In this report we have characterized the STC receptor and the
      functional targeting of ligand and receptor to mitochondria. For receptor binding
      analysis, a stanniocalcin-alkaline phosphatase fusion protein was engineered.
      Subsequent binding assays using the fusion protein indicated that kidney and
      liver contained the highest number of binding sites with affinities of 0.8 and
      0.25 nm, respectively. Intriguingly, purified mitochondria from both tissues
      yielded similar high affinity binding sites. Fractionation analysis revealed that
      the majority of binding sites were localized to the inner mitochondrial membrane.
      In further studies, we characterized the time course of STC-alkaline phosphatase
      fusion protein sequestration by intact mitochondria. In situ ligand binding also
      revealed discrete, displaceable binding to plasma membranes and mitochondria of
      nephron cells and liver hepatocytes. The existence of mitochondrial receptors
      prompted a similar search for the ligand. Immunogold electron microscopy revealed
      that STC was preferentially concentrated in the mitochondria of all nephron
      segments targeted by STC. Subcellular fractionation revealed that >90% of
      cellular STC immunoreactivity was mitochondrial, confined to the inner matrix,
      and similar in size to recombinant STC (50 kDa). In functional studies,
      recombinant STC had concentration-dependent stimulatory effects on electron
      transfer by sub-mitochondrial particles. Collectively the evidence implies a role
      for STC in cell metabolism.

PMID- 12223481
TI  - The human homolog of the rat inositol phosphate multikinase is an inositol
      1,3,4,6-tetrakisphosphate 5-kinase.
AB  - We have demonstrated that the human homolog of the rat inositol phosphate
      multikinase is an inositol 1,3,4,6-tetrakisphosphate 5-kinase (InsP(4) 5-kinase).
      The cDNA of the human gene contained a putative open reading frame of 1251 bp
      encoding 416 amino acids with 83.6% identity compared with the rat protein. The
      substrate specificity of the recombinant human protein demonstrated preference
      for Ins(1,3,4,6)P(4) with a catalytic efficiency (V(max)/K(m)) 43-fold greater
      than that of Ins(1,3,4,5)P(4) and 2-fold greater than that of Ins(1,4,5)P(3). The
      apparent V(max) was 114 nmol of Ins(1,3,4,5,6)P(5) formed/min/mg of protein, and
      the apparent K(m) was 0.3 microm Ins(1,3,4,6)P(4). The functional homolog in
      yeast is Ipk2p, and ipk2-null yeast strains do not synthesize Ins(1,3,4,5,6)P(5)
      or InsP(6). Synthesis of these compounds was restored by transformation with wild
      type yeast IPK2 but not with human InsP(4) 5-kinase. Thus the human gene does not
      complement for the loss of the yeast gene because yeast cells do not contain the
      substrate Ins(1,3,4,6)P(4), and the reaction of the human protein with
      Ins(1,3,4,5)P(4) is insufficient to effect rescue or synthesis of InsP(5) and
      InsP(6). Therefore the major activity of human InsP(4) 5-kinase is
      phosphorylation at the D-5 position, and the pathways for synthesis of
      Ins(1,3,4,5,6)P(5) in yeast versus humans are different.

PMID- 12223482
TI  - The membrane biogenesis peroxin Pex16p. Topogenesis and functional roles in
      peroxisomal membrane assembly.
AB  - Previously we isolated human PEX16 encoding 336-amino acid-long peroxin Pex16p
      and showed that its dysfunction was responsible for Zellweger syndrome of
      complementation group D (group 9). Here we have determined the membrane topology
      of Pex16p by differential permeabilization method: both N- and C-terminal parts
      are exposed to the cytosol. In the search for Pex16p topogenic sequence, basic
      amino acids clustered sequence, RKELRKKLPVSLSQQK, at positions 66-81 and the
      first transmembrane segment locating far downstream, nearly by 40 amino acids, of
      this basic region were defined to be essential for integration into peroxisome
      membranes. Localization to peroxisomes of membrane proteins such as Pex14p,
      Pex13p, and PMP70 was interfered with in CHO-K1 cells by a higher level
      expression of the pex16 patient-derived dysfunctional but topogenically active
      Pex16pR176ter comprising resides 1-176 or of the C-terminal cytoplasmic part
      starting from residues at 244 to the C terminus. Furthermore, Pex16p C-terminal
      cytoplasmic part severely abrogated peroxisome restoration in pex mutants such as
      matrix protein import-defective pex12 and membrane assembly impaired pex3 by
      respective PEX12 and PEX3 expression, whereas the N-terminal cytosolic region did
      not affect restoration. These results imply that Pex16p functions in peroxisome
      membrane assembly, more likely upstream of Pex3p.

PMID- 12223483
TI  - AAT-1, a novel testis-specific AMY-1-binding protein, forms a quaternary complex
      with AMY-1, A-kinase anchor protein 84, and a regulatory subunit of cAMP
      dependent protein kinase and is phosphorylated by its kinase.
AB  - AMY-1 has been identified by us as a c-Myc-binding protein and was found to
      stimulate c-Myc transcription activity. AMY-1 was also found to be associated
      with protein kinase A anchor protein 84/149 (S-AKAP84/AKAP149) in the
      mitochondria in somatic cells and sperm, suggesting that it plays a role in
      spermatogenesis. To determine the molecular function of AMY-1, a two-hybrid
      screening of cDNAs encoding AMY-1-binding proteins was carried out with AMY-1 as
      a bait using a human testis cDNA library, and a clone encoding a novel protein,
      AAT-1, was obtained. Three isoforms of AAT-1, AAT-1alpha, -beta, and -gamma, were
      found to be derived from an alternative splicing of the transcripts of the aat-1
      gene, which was mapped at human chromosome 3q13-3q21. AAT-1 was found to be
      specifically expressed in the testis during the course of spermatogenesis and
      also to be present in the spermatid and mature sperm, as was AMY-1. AAT-1alpha
      was found to bind to and be colocalized in mitochondria with AMY-1 in human HeLa
      and mouse GC-1 cells. Furthermore, AAT-1alpha was found to bind to the N-terminal
      half of S-AKAP84/AKAP149 in a quaternary complex with AMY-1 and a regulatory
      subunit (RII) of cAMP-dependent kinase (PKA), in which AAT-1alpha was associated
      with RII via S-AKAP84/AKAP149, in rat testis and HeLa cells. It was then found
      that AAT-1alpha weakly stimulated a phosphorylation activity of PKA and also that
      AAT-1 itself was phosphorylated by PKA in vivo and in vitro. These results
      suggest that both AAT-1 and AMY-1 play roles in spermatogenesis.

PMID- 12223484
TI  - Ligand-dependent inhibition of oligomerization at the human thyrotropin receptor.
AB  - Recently, several studies have reported oligomerization of G protein-coupled
      receptors, although the functional implications of this phenomenon are still
      unclear. Using fluorescence resonance energy transfer (FRET) and
      coimmunoprecipitation (COIP), we previously reported that the human thyrotropin
      (TSH) receptor tagged with green fluorescent protein (TSHR(GFP)) and expressed in
      a heterologous system was present as oligomeric complexes on the cell surface.
      Here, we have extended this biophysical and biochemical approach to study the
      regulation of such oligomeric complexes. Co-expression of TSHR(GFP) and TSHR(Myc)
      constructs in Chinese hamster ovary cells resulted in FRET-positive cells. The
      specificity of the FRET signal was verified by the absence of energy transfer in
      individually transfected TSHR(GFP) and TSHR(Myc):Cy3 cells cultured together and
      also by acceptor photobleaching. Occupation of the receptor molecule by the
      ligand (TSH) resulted in a dose-dependent decrease in the FRET index from 20% in
      the absence of TSH to <1% with 10(3) microunits/ml of TSH. Such reduction in
      oligomeric forms was also confirmed by coimmunoprecipitation. Exposure of
      TSHR(GFP/Myc) cells to forskolin or cytochalasin D caused no change in the FRET
      index, confirming that the decrease in the oligomeric complexes was a receptor
      dependent phenomenon and free of energy or microtuble requirements. The TSH
      induced decrease in TSHR oligomers was found to be secondary to dissociation of
      the TSHR complexes as evidenced by an increase in fluorescent intensity of
      photobleached spots of GFP fluorescence with 10(3) microunits/ml of TSH. These
      data indicated that the less active conformation of the TSHR was comprised of
      receptor complexes and that such complexes were dissociated on the binding of
      ligand. Such observations support the concept of a constitutively active TSHR
      dimer or monomer that is naturally inhibited by the formation of higher order
      complexes. Inhibition of these oligomeric forms by ligand binding returns the
      TSHR to an activated state.

PMID- 12223485
TI  - Presenilin-dependent intramembrane proteolysis of CD44 leads to the liberation of
      its intracellular domain and the secretion of an Abeta-like peptide.
AB  - Alzheimer's disease (AD)-associated gamma-secretase is a presenilin (PS)-
      dependent proteolytic activity involved in the intramembraneous cleavage of the
      beta-amyloid precursor protein, Notch, LDL receptor-related protein, E-cadherin,
      and ErbB-4. This cut produces the corresponding intracellular domains (ICD),
      which are required for nuclear signaling of Notch and probably ErbB-4, the beta
      amyloid precursor protein, E-cadherin, and the LDL receptor-related protein as
      well. We have now investigated CD44, a cell surface adhesion molecule, which also
      undergoes an intramembraneous cleavage to liberate its ICD. We demonstrate that
      this cleavage requires a PS-dependent gamma-secretase activity. A loss-of
      function PS1 mutation, a PS1/PS2 knockout, as well as two independent and highly
      specific gamma-secretase inhibitors, abolish this cleavage. Surprisingly, small
      peptides similar to the amyloid beta-peptide (Abeta) are generated by an
      additional cut in the middle of the transmembrane region of CD44. Like Abeta,
      these CD44 beta-peptides are generated in a PS-dependent manner. These findings
      therefore suggest a dual intramembraneous cleavage mechanism mediated by PS
      proteins. The dual cleavage mechanism is required for nuclear signaling as well
      as removal of remaining transmembrane domains, a general function of PS in
      membrane protein metabolism.

PMID- 12223486
TI  - Crisscross enzymatic reaction between the two molecules in the active dimeric P69
      form of the 2'-5' oligodenylate synthetase.
AB  - 2'-5' oligoadenylate (2-5 (A)) synthetases are major components of the antiviral
      pathways induced by interferons. In the presence of double-stranded RNA, they
      polymerize ATP to form 2-5 (A) oligomers that, in turn, activate the latent
      ribonuclease RNase L, causing mRNA degradation. These enzymes, unlike other
      nucleotidyl transferases, catalyze 2'-5', not 3'-5', phosphodiester bond
      formation between substrates bound to the acceptor and donor sites. Moreover,
      unlike other members of this extended family, the P69 isozyme of 2-5 (A)
      synthetase functions as a homodimer. Here, we report that the need for P69
      dimerization is because of a crisscross enzyme reaction joining two substrate
      molecules bound to two opposite subunits. Consequently, although homodimers of
      mutants in the previously identified acceptor site, the donor site, or the
      catalytic site were inactive, selective heterodimers of the mutants were active
      because of subunit complementation. The catalytic site had to be present in the
      same subunit that contained the acceptor site, whereas the donor site had to be
      provided by the other subunit. These results allowed us to design a mutant
      protein that acted as a dominant-negative inhibitor of wt P69 but not of another
      isozyme of 2-5 (A) synthetase.

PMID- 12223487
TI  - The regulation of glycogen synthase kinase-3 nuclear export by Frat/GBP.
AB  - Previous studies have shown that nuclear levels of glycogen synthase kinase-3
      (GSK-3) are dynamically regulated and may affect access of GSK-3 to its
      substrates. In this study we show that the GSK-3-binding protein Frat/GBP
      regulates the nuclear export of GSK-3. We show that Frat/GBP contains a nuclear
      export sequence that promotes its own nuclear export and that of associated GSK
      3. Treating cells with leptomycin B increased nuclear levels of endogenous GSK-3
      suggesting that an endogenous process targets GSK-3 for nuclear export. To
      investigate this further, we used two approaches to disrupt the interaction
      between GSK-3 and endogenous Frat. First we isolated mutants of GSK-3 that
      selectively interfered with Frat binding and found that these mutants were poorly
      exported. Second we expressed a peptide that competes with Frat for GSK-3 binding
      and found that it caused endogenous GSK-3 to accumulate in the nucleus. Together
      these data suggest that Frat may be the endogenous factor that targets GSK-3 for
      nuclear export. The dynamic expression patterns of Frat mRNAs together with the
      role of Frat in mediating GSK-3 nuclear export have important implications for
      the control of the substrate access of GSK-3 in several signaling pathways.

PMID- 12223488
TI  - Homer regulates gain of ryanodine receptor type 1 channel complex.
AB  - Homer proteins form an adapter system that regulates coupling of group 1
      metabotropic glutamate receptors with intracellular inositol trisphosphate
      receptors and is modified by neuronal activity. Here, we demonstrate that Homer
      proteins also physically associate with ryanodine receptors type 1 (RyR1) and
      regulate gating responses to Ca(2+), depolarization, and caffeine. In contrast to
      the prevailing notion of Homer function, Homer1c (long form) and Homer1-EVH1
      (short form) evoke similar changes in RyR activity. The EVH1 domain mediates
      these actions of Homer and is selectively blocked by a peptide that mimics the
      Homer ligand. 1B5 dyspedic myotubes expressing RyR1 with a point mutation of a
      putative Homer-binding domain exhibit significantly reduced (approximately 33%)
      amplitude in their responses to K(+) depolarization compared with cells
      expressing wild type protein. These results reveal that in addition to its known
      role as an adapter protein, Homer is a direct modulator of Ca(2+) release gain.
      Homer is the first example of an "adapter" that also modifies signaling
      properties of its target protein. The present work reveals a novel mechanism by
      which Homer directly modulates the function of its target protein RyR1 and
      excitation-contraction coupling in skeletal myotubes. This form of regulation may
      be important in other cell types that express Homer and RyR1.

PMID- 12223489
TI  - Pitx factors are involved in basal and hormone-regulated activity of the human
      prolactin promoter.
AB  - The pituitary-specific POU homeodomain factor Pit-1 likely interacts with other
      factors for cell-specific expression of prolactin. Here we identify the paired
      like homeobox transcription factors Pitx1 and Pitx2 as factors functionally
      activating the proximal human prolactin promoter (hPRL-164luc). Using in vitro
      binding assays and a series of site-specific mutations of the proximal hPRL
      promoter, we mapped the B1 and B2 bicoid sites involved in Pitx-mediated
      transactivation of the hPRL-164luc construct. In somatolactotroph GH4C1 cells,
      basal proximal hPRL promoter activity was inhibited by a Pitx2 dominant-negative
      form in a dose-dependent manner, whereas binding disruptive mutations in the Pitx
      sites significantly reduced basal activity of the promoter. We also show that
      synergistic activation of hPRL-164luc by Pitx2 and Pit-1 requires the integrity
      of the B2 Pitx binding site, and at least one of the P1 and P2 Pit-1 response
      elements. In addition, mutation in the B2 Pitx site results in attenuation of the
      promoter's responsiveness to forskolin, thyrotropin-releasing hormone, and
      epidermal growth factor. Conversely, Pitx1 or Pitx2 overexpression in GH4C1 cells
      leads to an enhancement of the drugs stimulatory effects. Altogether, these
      results suggest that full responsiveness to several signaling pathways regulating
      the hPRL promoter requires the B2 Pitx binding site and that Pitx factors may be
      part of the proteic complex involved in these regulations. Finally, in situ
      hybridization analysis showing coexpression of the PRL and Pitx2 genes in rat and
      human lactotroph cells corroborates the physiological relevance of these results.

PMID- 12223490
TI  - Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in response to
      oxidative stress.
AB  - Oxidative stress induces JNK activation, which leads to apoptosis through
      mitochondria-dependent caspase activation. However, little is known about the
      mechanism by which JNK alters mitochondrial function. In this study, we
      investigated the role of phosphorylation of myeloid cell leukemia 1 (Mcl-1), an
      anti-apoptotic member of the Bcl-2 family, in oxidative stress-induced apoptosis.
      We found that JNK phosphorylated Ser-121 and Thr-163 of Mcl-1 in response to
      stimulation with H(2)O(2) and that transfection of unphosphorylatable Mcl-1
      resulted in an enhanced anti-apoptotic activity in response to stimulation with
      H(2)O(2). JNK-dependent phosphorylation and thus inactivation of Mcl-1 may be one
      of the mechanisms through which oxidative stress induces cellular damage.

PMID- 12223491
TI  - SUMO-1 modification of the C-terminal KVEKVD of Axin is required for JNK
      activation but has no effect on Wnt signaling.
AB  - Axin is a multifunctional protein, regulating Wnt signaling and the c-Jun N
      terminal/stress-activated protein kinase (JNK/SAPK) pathway as well as
      tumorigenesis. In the present study, we found that Axin interacts with three SUMO
      1 (small ubiquitin-related modifier) conjugating enzymes 3 (E3), PIAS1,
      PIASxbeta, and PIASy. The extreme C-terminal six amino acid residues of Axin are
      critical for the Axin/E3 interaction as deletion of the six residues
      (AxinDeltaC6) completely abolished the ability of Axin to interact with E3
      enzymes. AxinDeltaC6 also failed to activate JNK, although it was intact in both
      its interaction with MEKK1 and homodimerization. Consistent with the presence of
      a doublet of the KV(E/D) sumoylation consensus motif at the C-terminal end
      (KVEKVD), we found that Axin is heavily sumoylated. Deletion of the C-terminal
      six amino acids drastically reduced sumoylation, indicating that the C-terminal
      six amino acids stretch is the main sumoylation site for Axin. Sumoylation
      defective mutants failed to activate JNK but effectively destabilized beta
      catenin and attenuated LEF1 transcriptional activity. In addition, we show that
      dominant negative Axin mutants blocked PIAS-mediated JNK activation, in
      accordance with the requirement of sumoylation for Axin-mediated JNK activation.
      Taken together, we demonstrate that sumoylation plays a role for Axin to function
      in the JNK pathway.

PMID- 12223492
TI  - Location of the rhodamine-binding site in the human multidrug resistance P
      glycoprotein.
AB  - The human multidrug resistance P-glycoprotein (P-gp) pumps a wide variety of
      structurally diverse compounds out of the cell. It is an ATP-binding cassette
      transporter with two nucleotide-binding domains and two transmembrane (TM)
      domains. One class of compounds transported by P-gp is the rhodamine dyes. A P-gp
      deletion mutant (residues 1-379 plus 681-1025) with only the TM domains retained
      the ability to bind rhodamine. Therefore, to identify the residues involved in
      rhodamine binding, 252 mutants containing a cysteine in the predicted TM segments
      were generated and reacted with a thiol-reactive analog of rhodamine,
      methanethiosulfonate (MTS)-rhodamine. The activities of 28 mutants (in TMs 2-12)
      were inhibited by at least 50% after reaction with MTS-rhodamine. The activities
      of five mutants, I340C(TM6), A841C(TM9), L975C(TM12), V981C(TM12), and
      V982C(TM12), however, were significantly protected from inhibition by MTS
      rhodamine by pretreatment with rhodamine B, indicating that residues in TMs 6, 9,
      and 12 contribute to the binding of rhodamine dyes. These results, together with
      those from previous labeling studies with other thiol-reactive compounds,
      dibromobimane, MTS-verapamil, and MTS-cross-linker substrates, indicate that
      common residues are involved in the binding of structurally different drug
      substrates and that P-gp has a common drug-binding site. The results support the
      "substrate-induced fit" hypothesis for drug binding.

PMID- 12223493
TI  - Mapping of MST1 kinase sites of phosphorylation. Activation and
      autophosphorylation.
AB  - MST1 is a member of the Sterile-20 family of cytoskeletal, stress, and apoptotic
      kinases. MST1 is activated by phosphorylation at previously unidentified sites.
      This study examines the role of phosphorylation at several sites and effects on
      kinase activation. We define Thr(183) in subdomain VIII as a primary site of
      phosphoactivation. Thr(187) is also critical for kinase activity. Phosphorylation
      of MST1 in subdomain VIII was catalyzed by active MST1 via intermolecular
      autophosphorylation, enhanced by homodimerization. Active MST1 (wild-type or
      T183E), but not inactive Thr(183)/Thr(187) mutants, was also highly
      autophosphorylated at the newly identified Thr(177) and Thr(387) residues. Cells
      expressing active MST1 were mostly detached, whereas with inactive MST1, adhesion
      was normal. Active MKK4, JNK, caspase-3, and caspase-9 were detected in the
      detached cells. These cells also contained all autophosphorylated and essentially
      all caspase-cleaved MST1. Similar phenotypes were elicited by a caspase
      insensitive D326N mutant, suggesting that kinase activity, but not cleavage of
      MST1, is required. Interestingly, an S327E mutant mimicking Ser(327)
      autophosphorylation was also caspase-insensitive, but only when expressed in
      caspase-3-deficient cells. Together, these data suggest a model whereby MST1
      activation is induced by existing, active MST kinase, which phosphorylates
      Thr(183) and possibly Thr(187). Dimerization promotes greater phosphorylation.
      This leads to induction of the JNK signaling pathway, caspase activation, and
      apoptosis. Further activation of MST1 by caspase cleavage is best promoted by
      caspase-3, although this appears to be unnecessary for signaling and
      morphological responses.

PMID- 12223494
TI  - Inhibition of phosphatidylinositol-4-phosphate 5-kinase Ialpha impairs localized
      actin remodeling and suppresses phagocytosis.
AB  - Actin polymerization drives the extension of pseudopods required for
      phagocytosis. Phosphatidylinositol 4,5-bisphosphate (PIP(2)) is thought to play a
      central role in this process, because it interacts with several actin-regulatory
      proteins and undergoes acute and localized changes at sites of phagocytosis. We
      therefore studied whether phosphatidylinositol-4-phosphate 5-kinase (PIPK), the
      enzyme responsible for the generation of PIP(2) from phosphatidylinositol 4
      phosphate, is involved in the control of phagocytosis. PIPKIalpha was found to
      accumulate transiently on forming phagosomes. To test the functional involvement
      of PIPKIalpha in particle engulfment, we generated a double mutant (D309N/R427Q)
      that lacks kinase activity. When ectopically expressed in cultured cells, this
      mutant is targeted to the plasma membrane and accumulates at the phagosomal cup
      during particle engulfment. Expression of PIP5KIalpha D309N/R427Q impaired
      phagocytosis in RAW264.7 macrophages and in engineered phagocytes generated by
      transfection of Fc receptors in Chinese hamster ovary cells. Inhibition of
      phagocytosis could not be attributed to defects in particle binding or receptor
      clustering, which was monitored using green fluorescent protein-tagged Fcgamma
      receptors. Instead, expression of the inactive kinase diminished the accumulation
      of PIP(2) and of F-actin in the phagosomal cup. These data suggest that
      PIPKIalpha activity is involved in the actin remodeling that is a prerequisite
      for efficient phagocytosis. PIPKIalpha appears to contribute to the transient
      changes in PIP(2) levels that are associated with, and likely required for, the
      recruitment and regulation of actin-modulating proteins.

PMID- 12223495
TI  - Web-based three-dimensional Virtual Body Structures: W3D-VBS.
AB  - Major efforts are being made to improve the teaching of human anatomy to foster
      cognition of visuospatial relationships. The Visible Human Project of the
      National Library of Medicine makes it possible to create virtual reality-based
      applications for teaching anatomy. Integration of traditional cadaver and
      illustration-based methods with Internet-based simulations brings us closer to
      this goal. Web-based three-dimensional Virtual Body Structures (W3D-VBS) is a
      next-generation immersive anatomical training system for teaching human anatomy
      over the Internet. It uses Visible Human data to dynamically explore, select,
      extract, visualize, manipulate, and stereoscopically palpate realistic virtual
      body structures with a haptic device. Tracking user's progress through evaluation
      tools helps customize lesson plans. A self-guided "virtual tour" of the whole
      body allows investigation of labeled virtual dissections repetitively, at any
      time and place a user requires it.

PMID- 12223496
TI  - Simulated medical learning environments on the Internet.
AB  - Learning anatomy and surgical procedures requires both a conceptual understanding
      of three-dimensional anatomy and a hands-on manipulation of tools and tissue.
      Such virtual resources are not available widely, are expensive, and may be
      culturally disallowed. Simulation technology, using high-performance computers
      and graphics, permits realistic real-time display of anatomy. Haptics technology
      supports the ability to probe and feel this virtual anatomy through the use of
      virtual tools. The Internet permits world-wide access to resources. We have
      brought together high-performance servers and high-bandwidth communication using
      the Next Generation Internet and complex bimanual haptics to simulate a tool
      based learning environment for wide use. This article presents the technologic
      basis of this environment and some evaluation of its use in the gross anatomy
      course at Stanford University.

PMID- 12223497
TI  - Development and validation of assessment measures for a newly developed physical
      examination simulator.
AB  - OBJECTIVE: Define, extract and evaluate potential performance indicators from
      computer-generated data collected during simulated clinical female pelvic
      examinations. DESIGN: Qualitative and quantitative study analyzing computer
      generated simulator data and written clinical assessments collected from medical
      students who performed physical examinations on three clinically different pelvic
      simulators. SETTING: Introduction to patient care course at a major United States
      medical school. PARTICIPANTS: Seventy-three pre-clinical medical students
      performed 219 simulated pelvic examinations and generated 219 written clinical
      assessments. MEASUREMENTS: Cronbach's alpha for the newly defined performance
      indicators, Pearson's correlation of performance indicators with scored written
      clinical assessments of simulator findings. RESULTS: Four novel performance
      indicators were defined: time to perform a complete examination, number of
      critical areas touched during the exam, the maximum pressure used, and the
      frequency at which these areas were touched. The reliability coefficients (alpha)
      were time = 0.7240, critical areas = 0.6329, maximum pressure = 0.7701, and
      frequency = 0.5011. Of the four indicators, three correlated positively and
      significantly with the written clinical assessment scores: critical areas, p <
      0.01; frequency, p < 0.05; and maximum pressure, p < 0.05. CONCLUSION: This study
      demonstrates a novel method of analyzing raw numerical data generated from a
      newly developed patient simulator; deriving performance indicators from computer
      generated simulator data; and assessing validity of those indicators by comparing
      them with written assessment scores. Results show the new assessment measures
      provide an objective, reliable, and valid method of assessing students' physical
      examination techniques on the pelvic exam simulator.

PMID- 12223498
TI  - Modeling and simulation of pathways in menopause.
AB  - The analytical representation and simulation of complex molecular pathways can
      contribute to understanding and evaluating physiological as well as pathological
      processes. We are interested in modeling the processes of menopause to stratify
      women in terms of the genotypic and environmental components and their
      implications for development of individualized risk of postmenopausal disorders,
      e.g., breast and ovarian cancer, cardiovascular disease, and osteoporosis. We
      have initiated this study using the UltraSAN package to analyze the pathway
      associated with estrogen production. This model incorporates detailed information
      about the hormone factors affecting estrogen production, and the simulations
      carried out are based on published experimental data corresponding to hormone
      levels during the course of the normal female reproductive cycle. The agreement
      between the experimental data and the simulation is typically less than 2 ng/ml
      or 2 pg/ml respectively for progesterone and estradiol output. This approach
      further permits inclusion of information about an SNP observed in the gene coding
      for the enzyme aromatase as a model to study the impact of reduced enzymatic
      activity on hormone levels.

PMID- 12223499
TI  - Optimization of a research web environment for academic internal medicine
      faculty.
AB  - Usability evaluations are a powerful tool that can assist developers in their
      efforts to optimize the quality of their web environment. This underutilized,
      experimental method can serve to move applications toward true user-centered
      design. This article describes the usability methodology and illustrates its
      importance and application by describing a usability study undertaken at the Mayo
      Clinic for the purpose of improving an academic research web environment.
      Academic institutions struggling in an era of declining reimbursements are
      finding it difficult to maintain academic enterprises on the back of clinical
      revenues. This may result in declining amounts of time that clinical
      investigators have to spend in non-patient-related activities. For this reason,
      we have undertaken to design a web environment, which can minimize the time that
      a clinician-investigator needs to spend to accomplish academic instrumental
      activities of daily living. Usability evaluation is a powerful application of
      human factors engineering, which can improve the utility of web-based Informatics
      applications.

PMID- 12223500
TI  - Evaluating the capability of information technology to prevent adverse drug
      events: a computer simulation approach.
AB  - BACKGROUND: The annual cost of morbidity and mortality due to medication errors
      in the U.S. has been estimated at $76.6 billion. Information technology
      implemented systematically has the potential to significantly reduce medication
      errors that result in adverse drug events (ADEs). OBJECTIVE: To develop a
      computer simulation model that can be used to evaluate the effectiveness of
      information technology applications designed to detect and prevent medication
      errors that result in adverse drug effects. METHODS: A computer simulation model
      was constructed representing the medication delivery system in a hospital.
      STELLA, a continuous simulation software package, was used to construct the
      model. Parameters of the model were estimated from a study of prescription errors
      on two hospital medical/surgical units and used in the baseline simulation. Five
      prevention strategies were simulated based on information obtained from the
      literature. RESULTS: The model simulates the four stages of the medication
      delivery system: prescribing, transcribing, dispensing, and administering drugs.
      We simulated interventions that have been demonstrated in prior studies to
      decrease error rates. The results suggest that an integrated medication delivery
      system can save up to 1,226 days of excess hospitalization and $1.4 million in
      associated costs annually in a large hospital. The results of the analyses
      regarding the effects of the interventions on the additional hospital costs
      associated with ADEs are somewhat sensitive to the distribution of errors in the
      hospital, more sensitive to the costs of an ADE, and most sensitive to the
      proportion of medication errors resulting in ADEs. CONCLUSIONS: The results
      suggest that clinical information systems are potentially a cost-effective means
      of preventing ADEs in hospitals and demonstrate the importance of viewing
      medication errors from a systems perspective. Prevention efforts that focus on a
      single stage of the process had limited impact on the overall error rate. This
      study suggests that system-wide changes to the medication delivery system are
      required to drastically reduce mediation errors that may result in ADEs in a
      hospital setting.

PMID- 12223501
TI  - Exploring issues of quality of service in a Next Generation Internet testbed: a
      case study using PathMaster.
AB  - This case study describes a project that explores issues of quality of service
      (QoS) relevant to the next-generation Internet (NGI), using the PathMaster
      application in a testbed environment. PathMaster is a prototype computer system
      that analyzes digitized cell images from cytology specimens and compares those
      images against an image database, returning a ranked set of "similar" cell images
      from the database. To perform NGI testbed evaluations, we used a cluster of nine
      parallel computation workstations configured as three subclusters using Cisco
      routers. This architecture provides a local "simulated Internet" in which we
      explored the following QoS strategies: (1) first-in-first-out queuing, (2)
      priority queuing, (3) weighted fair queuing, (4) weighted random early detection,
      and (5) traffic shaping. The study describes the results of using these
      strategies with a distributed version of the PathMaster system in the presence of
      different amounts of competing network traffic and discusses certain of the
      issues that arise. The goal of the study is to help introduce NGI QoS issues to
      the Medical Informatics community and to use the PathMaster NGI testbed to
      illustrate concretely certain of the QoS issues that arise.

PMID- 12223503
TI  - Military research needs in biomedical informatics.
AB  - The 2001 U.S. Army Medical Research and Materiel Command (USAMRMC) Biomedical
      Informatics Roadmap Meeting was devoted to developing a strategic plan in four
      focus areas: Hospital and Clinical Informatics, E-Health, Combat Health
      Informatics, and Bioinformatics and Biomedical Computation. The driving force of
      this Roadmap Meeting was the recent accelerated pace of change in biomedical
      informatics in which emerging technologies have the potential to affect
      significantly the Army research portfolio and investment strategy in these focus
      areas. The meeting was structured so that the first two days were devoted to
      presentations from experts in the field, including representatives from the three
      services, other government agencies, academia, and the private sector, and the
      morning of the last day was devoted to capturing specific biomedical informatics
      research needs in the four focus areas. This white paper summarizes the key
      findings and recommendations and should be a powerful tool for the crafting of
      future requests for proposals to help align USAMRMC new strategic research
      investments with new developments and emerging technologies.

PMID- 12223502
TI  - Basic microbiologic and infection control information to reduce the potential
      transmission of pathogens to patients via computer hardware.
AB  - Computer technology from the management of individual patient medical records to
      the tracking of epidemiologic trends has become an essential part of all aspects
      of modern medicine. Consequently, computers, including bedside components, point
      of-care testing equipment, and handheld computer devices, are increasingly
      present in patients' rooms. Recent articles have indicated that computer
      hardware, just as other medical equipment, may act as a reservoir for
      microorganisms and contribute to the transfer of pathogens to patients. This
      article presents basic microbiological concepts relative to infection, reviews
      the present literature concerning possible links between computer contamination
      and nosocomial colonizations and infections, discusses basic principles for the
      control of contamination, and provides guidelines for reducing the risk of
      transfer of microorganisms to susceptible patient populations.

PMID- 12223504
TI  - Recognition of critical situations from time series of laboratory results by case
      based reasoning.
AB  - OBJECTIVE: To develop a technique for recognizing critical situations based on
      laboratory results in settings in which a normal range cannot be defined, because
      what is "normal" differs widely from patient to patient. To assess the potential
      of this approach for kidney transplant recipients, where recognition of acute
      rejections is based on the pattern of changes in serum creatinine. DESIGN: We
      developed a case-based reasoning algorithm using dynamic time-warping as the
      measure of similarity which allows comparison of series of infrequent
      measurements at irregular intervals for retrieval of the most similar historical
      cases for the assessment of a new situation. MEASUREMENTS: The ability to
      recognize creatinine courses associated with an acute rejection was tested for a
      set of cases from a database of transplant patient records and compared with the
      diagnostic performance of experienced physicians. Tests were performed with case
      bases of various sizes. RESULTS: The accuracy of the algorithm increased steadily
      with the size of the available case base. With the largest case bases, the case
      based algorithm reached an accuracy of 78 +/- 2%, which is significantly higher
      than the performance of experienced physicians (69 +/- 5.3%) (p < 0.001).
      CONCLUSION: The new case-based reasoning algorithm with dynamic time warping as
      the measure of similarity allows extension of the use of automatic laboratory
      alerting systems to conditions in which abnormal laboratory results are the norm
      and critical states can be detected only by recognition of pathological changes
      over time.

PMID- 12223505
TI  - Immediate benefits realized following implementation of physician order entry at
      an academic medical center.
AB  - OBJECTIVE: To evaluate the benefits of computerized physician order entry (POE)
      and electronic medication administration record (eMAR) on the delivery of health
      care. DESIGN: Inpatient nursing units in an academic health system were the
      setting for the study. The study comprised before-and-after comparisons between
      phase 1, pre-implementation of POE (pre-POE) and phase 2, post-implementation of
      POE (post-POE) and, within phase 2, a comparison of POE and the combination of
      POE plus eMAR. Length of stay and cost were compared pre- and post-POE for a
      period of 10 to 12 months across all services in the respective hospitals.
      MEASUREMENTS: Comparisons were made pre- and post-POE for the time intervals
      between initiation and completion of pharmacy (pre-POE, n=46; post-POE, n=70),
      radiology (pre-POE, n=11; post-POE, n=54), and laboratory orders (without POE,
      n=683; with POE, n=1,142); timeliness of countersignature of verbal order
      (University Hospitals [OSUH]: pre-POE, n=605; post-POE, n=19,225; James Cancer
      Hospital (James): pre-POE, n=478; post-POE, n=10,771); volume of nursing
      transcription errors (POE with manual MAR, n=888; POE with eMAR, n=396); length
      of stay and total cost (OSUH: pre-POE, n=8,228; post-POE, n=8,154; James: (pre
      POE, n=6,471; post-POE, n=6,045). RESULTS: Statistically significant reductions
      were seen following the implementation of POE for medication turn-around times
      (64 percent, from 5:28 hr to 1:51 hr; p<0.001), radiology procedure completion
      times (43 percent, from 7:37 hr to 4:21 hr; p<0.05), and laboratory result
      reporting times (25 percent, from 31:3 min to 23:4 min; p=0.001). In addition,
      POE combined with eMAR eliminated all physician and nursing transcription errors.
      There were 43 and 26 percent improvements in order countersignature by physicians
      in OSUH and James, respectively. Severity-adjusted length of stay decreased in
      OSUH (pre-POE, 3.91 days; post-POE, 3.71 days; p=0.002), but not significantly in
      James (pre-POE, 3.68 days; post-POE, 3.61 days; p=0.356). Although total cost per
      admission decreased significantly in selected services, it did not change
      significantly across either institution (OSUH: pre-POE, 5,697 dollars; post-POE,
      5,661 dollars; p=0.687; James: pre-POE, 6,427 dollars; post-POE, 6,518 dollars;
      p=0.502). CONCLUSION: Physician order entry and eMAR provided the framework for
      improvements in patient safety and in the timeliness of care. The significant
      cultural and workflow changes that accompany the implementation of POE did not
      adversely affect acuity-adjusted length of stay or total cost. The reductions in
      transcription errors, medication turn-around times, and timely reporting of
      results supports the view that POE and eMAR provide a good return on investment.

PMID- 12223506
TI  - Improving patient safety by identifying side effects from introducing bar coding
      in medication administration.
AB  - OBJECTIVE: In addition to providing new capabilities, the introduction of
      technology in complex, sociotechnical systems, such as health care and aviation,
      can have unanticipated side effects on technical, social, and organizational
      dimensions. To identify potential accidents in the making, the authors looked for
      side effects from a natural experiment, the implementation of bar code medication
      administration (BCMA), a technology designed to reduce adverse drug events
      (ADEs). DESIGN: Cross-sectional observational study of medication passes before
      (21 hours of observation of 7 nurses at 1 hospital) and after (60 hours of
      observation of 26 nurses at 3 hospitals) BCMA implementation. MEASUREMENTS:
      Detailed, handwritten field notes of targeted ethnographic observations of in
      situ nurse-BCMA interactions were iteratively analyzed using process tracing and
      five conceptual frameworks. RESULTS: Ethnographic observations distilled into 67
      nurse-BCMA interactions were classified into 12 categories. We identified five
      negative side effects after BCMA implementation: (1) nurses confused by automated
      removal of medications by BCMA, (2) degraded coordination between nurses and
      physicians, (3) nurses dropping activities to reduce workload during busy
      periods, (4) increased prioritization of monitored activities during goal
      conflicts, and (5) decreased ability to deviate from routine sequences.
      CONCLUSION: These side effects might create new paths to ADEs. We recommend
      design revisions, modification of organizational policies, and "best practices"
      training that could potentially minimize or eliminate these side effects before
      they contribute to adverse outcomes.

PMID- 12223507
TI  - A focus on simulation in medical informatics.

PMID- 12223508
TI  - Macrophages in gene therapy: cellular delivery vehicles and in vivo targets.
AB  - The appearance and activation of macrophages are thought to be rapid events in
      the development of many pathological lesions, including malignant tumors,
      atherosclerotic plaques, and arthritic joints. This has prompted recent attempts
      to use macrophages as novel cellular vehicles for gene therapy, in which
      macrophages are genetically modified ex vivo and then reintroduced into the body
      with the hope that a proportion will then home to the diseased site. Here, we
      critically review the efficacy of various gene transfer methods (viral,
      bacterial, protozoan, and various chemical and physical methods) in transfecting
      macrophages in vitro, and the results obtained when transfected macrophages are
      used as gene delivery vehicles. Finally, we discuss the use of various viral and
      nonviral methods to transfer genes to macrophages in vivo. As will be seen,
      definitive evidence for the use of macrophages as gene transfer vehicles has yet
      to be provided and awaits detailed trafficking studies in vivo. Moreover,
      although methods for transfecting macrophages have improved considerably in
      efficiency in recent years, targeting of gene transfer specifically to
      macrophages in vivo remains a problem. However, possible solutions to this
      include placing transgenes under the control of macrophage-specific promoters to
      limit expression to macrophages or stably transfecting CD34(+) precursors of
      monocytes/macrophages and then differentiating these cells into
      monocytes/macrophages ex vivo. The latter approach could conceivably lead to the
      bone marrow precursor cells of patients with inherited genetic disorders being
      permanently fortified or even replaced with genetically modified cells.

PMID- 12223509
TI  - The viral manipulation of the host cellular and immune environments to enhance
      propagation and survival: a focus on RNA viruses.
AB  - Virus infection presents a significant challenge to host survival. The capacity
      of the virus to replicate and persist in the host is dependent on the status of
      the host antiviral defense mechanisms. The study of antiviral immunity has
      revealed effective antiviral host immune responses and enhanced our knowledge of
      the diversity of viral immunomodulatory strategies that undermine these defences.
      This review describes the diverse approaches that are used by RNA viruses to
      trick or evade immune detection and response systems. Some of these approaches
      include the specific targeting of the major histocompatibility complex-restricted
      antigen presentation pathways, apoptosis, disruption of cytokine function and
      signaling, exploitation of the chemokine system, and interference with humoral
      immune responses. A detailed insight into interactions of viruses with the immune
      system may provide direction in the development of new vaccine strategies and
      novel antiviral compounds.

PMID- 12223510
TI  - Orphan nuclear receptors in T lymphocyte development.
AB  - Lymphocyte development is initiated from hematopoietic stem cells and can be
      divided into multiple phenotypically distinct stages. Transcription factors play
      important roles in programming the developmental process of lymphocytes. Recent
      studies have identified key roles of several orphan nuclear receptors in T
      lymphocyte development. The orphan nuclear receptor RORgamma has been shown to
      promote thymocyte survival by activating the expression of antiapoptotic protein
      Bcl-x(L). RORgamma is also required for the development of lymph nodes and
      Peyer's patches. The orphan receptors Nur77 and Nor1 are involved in TCR-mediated
      cell death and thymocyte-negative selection. These studies provide novel insights
      into the molecular mechanisms of T lymphocyte development.

PMID- 12223511
TI  - CpG-DNA stimulates cellular and humoral immunity and promotes Th1 differentiation
      in aged BALB/c mice.
AB  - We examined whether CpG-DNA could be used as adjuvant to induce a T helper cell
      type-1 (Th1) immunity in aged BALB/c mice that showed a Th2 polarization.
      Bordetella pertussis and complete Freund's adjuvant (CFA) were used as well.
      Immunization with ovalbumin (OVA)/CpG-DNA showed that the immunoglobulin G
      (IgG)2a/IgG1 ratio and OVA-specific T cell response were similar in young and
      aged mice. OVA/CpG-DNA induced the secretion of interferon-gamma (IFN-gamma) and
      absence of interleukin (IL)-5. Similar results were found in mice immunized with
      OVA/CFA. When mice were immunized with OVA/B. pertussis, we found that the
      IgG2a/IgG1 ratio and OVA-specific T cell response were lower in aged mice and
      elicited IFN-gamma and IL-5. In vitro CpG-DNA stimulated antigen-presenting cells
      to display IL-12 and up-regulate the expression of major histocompatibility
      complex class II and B7-2 on B cells as efficiently in aged as in young mice, but
      the up-regulation of B7-1 was stronger in aged mice. The findings demonstrate
      that CpG-DNA is able to induce a young-like Th1 specific immune response in aged
      mice.

PMID- 12223512
TI  - Molecular mechanisms of platelet-mediated leukocyte recruitment during myocardial
      reperfusion.
AB  - Leukocyte interaction with platelets and endothelial cells as cause of myocardial
      stunning was investigated. Mice were anesthetized and, after thoracotomy, the LAD
      was ligated for 20 min. Where indicated, rhodamine 6G for leukocyte labeling,
      fluorescence-labeled platelets, and the GPIIb/IIIa antagonist Tirofiban were
      infused at the onset of reperfusion in vivo. After 15 min, hearts were quickly
      excised and analyzed by fluorescence microscopy or assessed for left ventricular
      developed pressure (LVDP). After in vivo ischemia and reperfusion, leukocyte
      retention in the heart was 55 +/- 5/field in wild-type hearts, 38 +/- 3/field in
      P-selectin-/- hearts, and 23 +/- 4/field in P-selectin/intercellular adhesion
      molecule-1 (ICAM-1)-/- hearts. Postischemic LVDP (48+/-4 mmHg in wild-type
      hearts) improved in P-selectin-/- and P-selectin/ICAM-1-/- hearts (58+/-4 and
      79+/-6 mmHg). Tirofiban reduced platelet adhesion (23+/-4/field vs. 61+/-2/field
      in wild-type hearts) and leukocyte recruitment (34+/-2/field), improving LVDP
      (63+/-4 mmHg). Whereas wild-type platelets displayed similar adherence to P
      selectin/ICAM-1-/- hearts as platelets from the same genetic strain (63+/-3 vs.
      61+/-4 platelets/field), wild-type platelet infusion restored postischemic
      leukocyte recruitment in P-selectin/ICAM-1-/- hearts (55+/-4/field vs. 23+/
      4/field), an effect sensitive to Tirofiban inhibition (23+/-4 leukocytes/field,
      22+/-3 platelets/field). We conclude that platelets contribute postischemic
      leukocyte adhesion in the heart via P-selectin and GPIIb/IIIa.

PMID- 12223513
TI  - Identification of human cysteine-rich secretory protein 3 (CRISP-3) as a matrix
      protein in a subset of peroxidase-negative granules of neutrophils and in the
      granules of eosinophils.
AB  - Cysteine-rich secretory protein 3 (CRISP-3; also known as SGP28) was originally
      discovered in human neutrophilic granulocytes. We have recently developed a
      sensitive sandwich enzyme-linked immunosorbent assay for CRISP-3 and demonstrated
      the presence of CRISP-3 in exocrine secretions. To investigate the subcellular
      localization and mobilization of CRISP-3 in human neutrophils, we performed
      subcellular fractionation of resting and activated neutrophils on three-layer
      Percoll density gradients, release-studies of granule proteins in response to
      different secretagogues, and double-labeling immunogold electron microscopy.
      CRISP-3 was found to be localized in a subset of granules with overlapping
      characteristics of specific and gelatinase granules and mobilized accordingly,
      thus confirming the hypothesis that peroxidase-negative granules exist as a
      continuum from specific to gelatinase granules regarding protein content and
      mobilization. CRISP-3 was found to be a matrix protein, which is stored in
      granules as glycosylated and as unglycosylated protein. The subcellular
      distribution of the two forms of CRISP-3 was identical. In addition, CRISP-3 was
      found as a granule protein in eosinophilic granulocytes. The presence of CRISP-3
      in peroxidase-negative granules of neutrophils, in granules of eosinophils, and
      in exocrine secretions indicates a role in the innate host defense.

PMID- 12223514
TI  - Binding of function-blocking mAbs to mouse and human P-selectin glycoprotein
      ligand-1 peptides with and without tyrosine sulfation.
AB  - P-selectin glycoprotein ligand-1 (PSGL-1) mediates rolling of leukocytes on P
      selectin-expressing endothelial cells under shear flow. Function-blocking
      monoclonal antibodies (mAbs) against mouse and human PSGL-1 recognize an anionic
      segment at the N-terminus of PSGL-1. High affinity interaction of PSGL-1 with P
      selectin requires sulfation of tyrosines 46, 48, and 51 (human) or 54 and 56
      (mouse). We tested binding of two anti-human (KPL1 and PL1) and two anti-mouse
      (4RA10 and 2PH1) PSGL-1 mAbs to synthetic peptides of N-terminus of human and
      mouse PSGL-1 and found binding to be independent of tyrosine sulfation. In
      peptide-blocking experiments, sulfated and nonsulfated human and mouse peptides
      competed with antibody binding to PSGL-1 expressed on myeloid cells.
      Arylsulfatase treatment significantly reduced P-selectin binding but had no
      effect on antibody binding. Our data show, in three independent assay systems,
      that function-blocking antibodies to mouse or human PSGL-1 do not require
      sulfation of N-terminal tyrosines for binding.

PMID- 12223515
TI  - Molecular characterization and expression analysis of leucine-rich alpha2
      glycoprotein, a novel marker of granulocytic differentiation.
AB  - Using data obtained from cDNA representational difference analysis to identify
      genes induced during neutrophilic differentiation of the 32D clone 3G (32Dcl3G)
      cells, we isolated cDNA clones for murine and human leucine-rich alpha2
      glycoprotein (hLRG), a protein with unknown function purified 25 years ago.
      Expression of LRG during differentiation of 32Dcl3G cells preceded the expression
      of lactoferrin and gelatinase but followed myeloperoxidase. LRG transcripts were
      also detected in human neutrophils and progenitor cells but not in peripheral
      blood mononuclear cells. Notably, LRG expression was up-regulated during
      neutrophilic differentiation of human MPD and HL-60 cells but down-regulated
      during monocytic differentiation of HL-60 cells. The hLRG gene was localized to
      chromosome 19p13.3, a region to which the genes for several neutrophil granule
      enzymes also map. The putative promoter region of LRG was found to contain
      consensus-binding sites for PU.1, C/EBP, STAT, and MZF1. These results suggest
      that LRG is a novel marker for early neutrophilic granulocyte differentiation.

PMID- 12223516
TI  - Interferon-gamma stimulates the expression of galectin-9 in cultured human
      endothelial cells.
AB  - Galectin-9 is a member of the galectin family and has been identified as an
      eosinophil chemoattractant produced by activated T lymphocytes. Vascular
      endothelial cells play an important role in the initial step of eosinophil
      recruitment and activation in immune and inflammatory responses. We have
      addressed the stimulation of galectin-9 expression in endothelial cells. Galectin
      9 was detected in membrane and cytosolic fractions of human umbilical vein
      endothelial cells stimulated with interferon-gamma (IFN-gamma). IFN-gamma also
      enhanced the adhesion of human eosinophilic leukemia-1 cells to endothelial
      monolayers, and it was inhibited by the presence of lactose. Interleukin-4, which
      induces eotaxin expression, did not affect the expression of galectin-9. The in
      situ endothelium from patients with inflammatory diseases was found to express
      galectin-9. IFN-gamma-induced production of galectin-9 by endothelial cells may
      play an important role in immune responses by regulating interactions between the
      vascular wall and eosinophils.

PMID- 12223518
TI  - Interleukin-10 inhibits proinflammatory activation of endothelium in response to
      Borrelia burgdorferi or lipopolysaccharide but not interleukin-1beta or tumor
      necrosis factor alpha.
AB  - Interleukin (IL)-10 is generally regarded as an anti-inflammatory cytokine, since
      it acts on a variety of cell types to suppress production of proinflammatory
      mediators. In inflammation, endothelial cells (EC) play a crucial role in
      recruiting leukocytes to sites of injury or infection. In this study, the actions
      of IL-10 on human umbilical vein EC were investigated. IL-10 reduced migration of
      monocytes and T lymphocytes across endothelium stimulated by lipopolysaccharide
      and decreased endothelial production of chemokines in response to
      lipopolysaccharide and Borrelia burgdorferi, the agent of Lyme disease. However,
      IL-10 did not affect these responses when EC were activated by the host
      proinflammatory cytokines IL-lbeta or tumor necrosis factor alpha. Moreover, IL
      10 did not prevent up-regulation of the adhesion molecules E-selectin and
      intercellular adhesion molecule-1 by EC exposed to any of these activating
      agents. IL-10 therefore inhibits proinflammatory activation of EC in a manner
      that is selective with respect to stimulus and effector response.

PMID- 12223517
TI  - The role of ceramide of human macrophage gangliosides in activation of human
      macrophages.
AB  - Gangliosides of macrophages have immunoregulatory and structural attributes,
      distinct from neural gangliosides. We previously produced a monoclonal antibody
      to human macrophage gangliosides (HMG; mAb25F4), which inhibited macrophage
      migration and recognized a surface-accessible epitope. We investigated expanded
      immunoregulatory properties and molecular domains for antibody recognition.
      mAb25F4 directly induced human macrophage production of proinflammatory
      cytokines, interleukin-1beta, and tumor necrosis factor alpha. Conditions were
      established for selective, reversible depletion of HMG with D-threo-(R,R)-1
      phenyl-2-decanoyl-amino-3-morpholine-1-propanol. mAb25F4 had diminished
      recognition for ganglioside-depleted macrophages, which was restored with
      regeneration of gangliosides. Although desialylation of HMG did not impair
      mAb25F4 recognition, enzymatic cleavage of ceramide abolished antibody binding.
      Antibody recognition was specific for the ceramide fraction, with preferential
      recognition for ceramide of HMG and murine macrophage gangliosides and limited
      recognition for neural tissue ceramide and gangliosides. This study underscores
      the importance of structurally distinct ceramide of macrophage gangliosides as a
      critical domain for ganglioside-mediated activation of human macrophages.

PMID- 12223519
TI  - Human pregnancy-specific glycoprotein 1a (PSG1a) induces alternative activation
      in human and mouse monocytes and suppresses the accessory cell-dependent T cell
      proliferation.
AB  - It has been proposed that pregnancy-specific factors induce the suppression of a
      specific arm of the maternal response accompanied by activation of the
      nonspecific, innate immune system. The aim of this study was to determine whether
      pregnancy-specific glycoprotein 1a (PSG1a), the major variant of PSG
      polypeptides, is able to modulate the monocyte/macrophage (Mo) metabolism to
      regulate T cell activation and proliferation. Using the recombinant form of this
      glycoprotein (rec-PSG1a), expressed in mammalian cells with a vaccinia-based
      expression vector, we have demonstrated that human PSG1a induces arginase
      activity in peripheral blood human Mo and human and murine Mo cell lines. In
      addition, rec-PSG1a is able to induce alternative activation because it up
      regulates the arginase activity and inhibits the nitric oxide production in Mo
      activated by lipopolysaccharides. We also observed that rec-PSG1a is an important
      accessory cells-dependent T cell suppressor factor that causes partial growth
      arrest at the S/G2/M phase of the cell cycle. Additionally, an impaired T cell
      proliferative response induced by mitogens and specific antigen was observed in
      BALB/c mice upon in vivo expression of PSG1a. Our results suggest that PSG1a
      function contributes to the immunomodulation during pregnancy, having opposite
      effects on maternal innate and adaptative systems.

PMID- 12223520
TI  - In vitro and in vivo activities of OX40 (CD134)-IgG fusion protein isoforms with
      different levels of immune-effector functions.
AB  - Recombinant fusion proteins consisting of the extracellular domain of
      immunoregulatory proteins and the constant domain of immunoglobulin G (IgG) are a
      novel class of human therapeutics. IgG isoforms exert different levels of immune
      effector functions, such as complement lysis and antibody-dependent cell
      cytotoxicity (ADCC). Several OX40-Ig fusion proteins were generated and compared
      in their potency to inhibit immune reactions. OX40-IgG fusion proteins act as
      decoys and inhibit T cell costimulation and extravasation induced by OX40 ligand
      expressing antigen-presenting cells (APC) and vascular endothelial cells,
      respectively. In addition, OX40-IgG1 protein induces ADCC and complement lysis in
      OX40 ligand-expressing cells. Replacement of the IgG1 by the IgG4 domain (OX40
      IgG4) eliminated complement lysis and reduced ADCC by half. Mutation of Leu(235)
      to Glu in IgG4 eliminated the remaining ADCC activity and generated a protein
      devoid of immune effector functions (OX40-IgG4mut). In vitro, OX40-IgG1 was more
      potent in inhibiting proliferation and cytokine release by peripheral blood
      mononuclear cells than OX40-IgG4mut, as OX40-IgG1 induced cell death in APC.
      However, both proteins reduced T cell-mediated colitis in mice to the same
      extent, indicating that in vivo neutralization of OX40L is sufficient. This study
      also demonstrates that effector functions of antibodies are retained and can be
      rationally designed in receptor-IgG fusion proteins.

PMID- 12223521
TI  - Macrophage accumulation at a site of renal inflammation is dependent on the M
      CSF/c-fms pathway.
AB  - Production of macrophage-colony stimulating factor (M-CSF), the major macrophage
      growth factor, is increased in tissues during inflammation. Therefore, we
      determined whether M-CSF, acting through its receptor c-fms, contributes to
      macrophage accumulation at a site of tissue injury. Daily treatment with anti-c
      fms or control antibody was given to mice with renal inflammation resulting from
      unilateral ureteric obstruction (UUO). Following UUO, kidney M-CSF mRNA increased
      in association with macrophage accumulation (days 1, 5, and 10) and local
      macrophage proliferation (days 5 and 10). Anti-c-fms treatment caused a minor
      inhibition of monocyte recruitment at day 1, reduced macrophage accumulation by
      75% at day 10, but did not affect blood monocyte counts or the CD4 and CD8
      lymphocytic infiltrate. Prevention of macrophage accumulation by anti-c-fms
      treatment was associated with a 90% reduction in local macrophage proliferation
      at days 5 and 10 without evidence of increased macrophage apoptosis. Therefore, M
      CSF/c-fms signaling plays a key role in macrophage accumulation during tissue
      injury.

PMID- 12223522
TI  - Disruption of CD40/CD40 ligand interaction with cleavage of CD40 on human
      gingival fibroblasts by human leukocyte elastase resulting in down-regulation of
      chemokine production.
AB  - CD40 is a crucial element in the process of fibroblast activation. We
      demonstrated that treatment of human gingival fibroblast (HGF) with human
      leukocyte elastase (HLE), a neutrophil serine protease, down-regulated the
      expression of CD40 and binding to the CD40 ligand (CD40L) using flow cytometry.
      The other neutrophil serine proteases, cathepsin G and proteinase 3, exhibited
      markedly less activity for CD40 reduction. The CD40 reduction by HLE was also
      observed in skin and lung fibroblasts, but not in monocytes, macrophages, and
      dendritic cells. The reduction resulted from direct proteolysis by HLE on the
      cell surface, because HLE reduced CD40 on fixed HGF and also on cell lysates and
      membranes. HLE treatment of HGF decreases interleukin (IL)-8 and macrophage
      chemoattractant protein-1 production by HGF when stimulated by CD40L, but not by
      IL-1alpha, suggesting that HLE inhibited a CD40-dependent cell activation. These
      results suggest that HLE possesses an anti-inflammatory effect for the HGF
      mediated inflammatory process.

PMID- 12223523
TI  - Multiple signals are required for maturation of human dendritic cells mobilized
      in vivo with Flt3 ligand.
AB  - The ligand for the receptor tyrosine kinase fms-like tyrosine kinase 3 (Flt3L) is
      a growth factor for hematopoietic progenitors and induces expansion of the two
      distinct lineages of dendritic cells (DC) that have been described in humans.
      These two lineages, DC1 and DC2, have been described according to their ability
      to induce naive T cell differentiation to T helper cell type 1 (Th1) and Th2
      effector cells, respectively. The immunoregulatory potential of DC1 and DC2
      depends on their state of maturation and activation, which can be mediated by
      several molecules. Because monocyte-derived DC1 produce interleukin-12 (IL-12)
      when stimulated with CD40 ligand (CD40L), we hypothesized that similar results
      would be obtained with DC1 mobilized by Flt3L. Unexpectedly, we found that
      immature DC expanded in vivo by Flt3L treatment could not be stimulated to
      produce IL-12 in vitro using CD40L and/or interferon-gamma (IFN-gamma) alone.
      Instead, we found that Flt3L-mobilized DC from cancer patients require a sequence
      of specific signals for maturation, which included initial treatment with
      granulocyte macrophage-colony stimulating factor followed by a combination of
      maturation signals such as CD40L and IFN-gamma. Flt3L-mobilized DC matured in
      this manner possessed greater T cell-stimulatory function than nonmatured DC. The
      ability to generate phenotypically mature, IL-12-producing DC1 from peripheral
      blood mononuclear cells mobilized by Flt3L will have important implications for
      the development of effective cancer immunotherapy strategies.

PMID- 12223524
TI  - RAW 264.7 macrophages induce apoptosis selectively in transformed fibroblasts:
      intercellular signaling based on reactive oxygen and nitrogen species.
AB  - The rationale for this study was to determine whether macrophages induce
      apoptosis selectively in transformed compared with nontransformed fibroblasts and
      to elucidate the underlying intercellular signaling chemistry. Murine fibroblasts
      transformed by oncogene expression (ras, src) or methylcholanthrene treatment
      were sensitive for apoptosis induction by RAW 264.7 macrophages, whereas parental
      cells and revertants were insensitive. Moreover, RAW 264.7 macrophages induced
      apoptosis in normal rat kidney (NRK) fibroblasts transiently transformed by
      epidermal growth factor/transforming growth factor-beta. Sensitivity for
      intercellular apoptosis induction was based on target cell-derived superoxide
      anions and effector cell-derived peroxidase and nitric oxide (NO). Superoxide
      anions dismutate to hydrogen peroxide, which is converted to HOCl by the
      peroxidase. The interaction of HOCl with superoxide anions then generates
      hydroxyl radicals. In parallel, NO interacts with superoxide anions and generates
      apoptosis-inducing peroxynitrite. Signaling by reactive oxygen and nitrogen
      species seems to represent a hitherto unrecognized signaling principle for the
      selective elimination of potential tumor cells by macrophages.

PMID- 12223525
TI  - The IL-12 response to herpes simplex virus is mainly a paracrine response of
      reactive inflammatory cells.
AB  - Herpes simplex virus (HSV) infection results in rapid and sustained up-regulation
      of interleukin (IL)-12, but the primary cellular source of IL-12 after HSV
      infection is unknown. We demonstrate that this cytokine largely derives from
      inflammatory cells rather than from productively infected epithelial cells. For
      optimal IL-12 induction, epithelial cells needed to be infected with replication
      competent virus, and cells needed to be able to synthesize proteins. Our results
      also indicate that HSV-infected cells generate intermediary products that signal
      recruited inflammatory cells, which themselves were not HSV-infected, to generate
      IL-12. Possible mechanisms by which infected cells communicate with inflammatory
      cells to cause IL-12 production are discussed.

PMID- 12223526
TI  - Effects of catecholamines on kinase activation in lung neutrophils after
      hemorrhage or endotoxemia.
AB  - Catecholamines are released in high levels after hemorrhage or endotoxemia and
      have been shown to modulate immune function, including cellular release of
      inflammatory mediators. In the present experiments, we examined the effects of
      endogenous and exogenous catecholamines on neutrophil accumulation and activation
      in the lungs using pretreatment with alpha- or beta-antagonists or alpha
      adrenergic agonists before hemorrhage or endotoxemia. These studies showed that
      alpha-, but not beta-adrenergic stimuli, modulated the severity of acute lung
      injury after hemorrhage or endotoxemia, and alpha-adrenergic stimuli was
      proinflammatory after hemorrhage but anti-inflammatory after endotoxemia. The
      observed alpha-adrenergic effects on lung neutrophil activation appeared to
      involve primarily the extracellular signal-regulated kinase pathway at the
      upstream kinase Raf, but not Ras. Although p38 and protein kinase A were
      activated in lung neutrophils after hemorrhage or endotoxemia, these kinases were
      not affected by alpha- or beta-adrenergic modulation. These results demonstrate
      that catecholamines have important immunomodulatory effects in vivo that affect
      intracellular signaling pathways in neutrophils and neutrophil-driven,
      inflammatory processes such as the development of acute lung injury.

PMID- 12223527
TI  - IL-13 signal transduction in human monocytes: phosphorylation of receptor
      components, association with Jaks, and phosphorylation/activation of Stats.
AB  - Interleukin (IL)-13 regulates monocyte function and is a potent stimulator of 15
      lipoxygenase expression. In different cell types, the functional IL-13 receptor
      complex can be comprised of variable protein components and has not been
      thoroughly examined in human monocytes. Here, we identify the receptor components
      and upstream signaling events initiated by IL-13 in primary human blood
      monocytes. The expression, phosphorylation and associated Jak kinases of the
      known, variable receptor components, IL-4R(alpha), IL-2Rgammac, IL-13R(alpha)1
      and IL-13R(alpha)2, were examined. We determined that IL-4R(alpha) and
      IL13R(alpha)1 are phosphorylated upon exposure to IL-13. Although IL-2Rgammac is
      also expressed, it is not phosphorylated upon exposure to IL-13. Evaluation of
      the presence of IL-13R(alpha)2 failed to reveal significant mRNA or protein
      expression. Earlier, our laboratory showed that IL-13 induced the phosphorylation
      of Jak2 and Tyk2 in monocytes and that expression of both Jaks was essential for
      downstream signaling by IL-13. Here, we report that Jak2 is associated with IL
      4R(alpha), and Tyk2 is associated with the IL-13R(alpha)1 component of the IL-13
      receptor complex. Additionally, Stat proteins 1alpha, 3, 5A, 5B, and 6 are
      phosphorylated in response to IL-13. Further, the nuclear translocation and DNA
      binding of each of these Stats were induced by IL-13. These data represent the
      first complete report of the functional IL-13 receptor complex and early
      signaling events in human monocytes. This information is critical for
      understanding the IL-13 response of monocytes in inflammation.

PMID- 12223528
TI  - Platelet factor 4 induces human natural killer cells to synthesize and release
      interleukin-8.
AB  - We provide evidence that platelet factor 4 (PF4), but not the related chemokine
      neutrophil-activating polypeptide-2, induced highly purified human natural killer
      (NK) cells to produce interleukin (IL)-8 in a time- and dosage-dependent manner.
      This ability was retained even while PF4 was bound to heparin. PF4 increased the
      steady state level of IL-8 mRNA, likely implying a transcriptional effect of PF4.
      Stimulation of NK cells through the Fc receptor for immunoglobulin G-IIIA was
      found to synergistically increase the effect of PF4 on IL-8 production but did
      not affect IL-2-related activities such as cytotoxic activity and proliferation.
      Pertussis toxin did not block the PF4-derived IL-8 production in NK cells, but
      this response was sensitive to wortmannin, implicating a role of
      phosphatidylinositol 3-kinase in the intracellular signaling pathway triggered by
      PF4. Our results characterize a new capacity for PF4 and provide further evidence
      for the pivotal role of NK cells in the environment of inflammation.

PMID- 12223529
TI  - Human dendritic cells express functional formyl peptide receptor-like-2 (FPRL2)
      throughout maturation.
AB  - Immature and mature dendritic cells (iDC and mDC, respectively) migrate to
      different anatomical sites, e.g., sites of antigen (Ag) deposition and secondary
      lymphoid organs, respectively, to fulfill their roles in the induction of
      primary, Ag-specific immune responses. The trafficking pattern of iDC and mDC is
      based on their expression of functional chemotactic receptors and the in vivo
      sites expressing the corresponding ligands including chemokines and/or classical
      chemoattractants. In this study, we have evaluated the expression of the formyl
      peptide receptor like-2 (FPRL2) by human iDC and mDC. We show that iDC respond
      chemotactically and by Ca(2+) mobilization to N-formyl-Met-Leu-Phe and a recently
      identified synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), whereas mDC
      derived from the same donor only respond to WKYMVm. Furthermore, iDC and mDC
      express FPRL2 mRNA and protein. As mDC do not express any other members of the
      human FPR subfamily, FPRL2 expressed by DC must be functional and mediate the
      effect of WKYMVm on DC. Indeed, treatment of iDC and mDC with WKYMVm induces the
      internalization of FPRL2. Thus, human myeloid DC express functional FPRL2 and
      maintain its expression even after maturation, suggesting that the interaction of
      FPRL2 and its endogenous ligand(s) may be involved in regulating DC trafficking
      during Ag uptake and processing in the periphery as well as the T cell
      stimulating phase of the immune responses.

PMID- 12223530
TI  - The therapeutic potential of poly(ADP-ribose) polymerase inhibitors.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is a member of the PARP enzyme family
      consisting of PARP-1 and several recently identified novel poly(ADP-ribosylating)
      enzymes. PARP-1 is an abundant nuclear protein functioning as a DNA nick-sensor
      enzyme. Upon binding to DNA breaks, activated PARP cleaves NAD(+) into
      nicotinamide and ADP-ribose and polymerizes the latter onto nuclear acceptor
      proteins including histones, transcription factors, and PARP itself. Poly(ADP
      ribosylation) contributes to DNA repair and to the maintenance of genomic
      stability. On the other hand, oxidative stress-induced overactivation of PARP
      consumes NAD(+) and consequently ATP, culminating in cell dysfunction or
      necrosis. This cellular suicide mechanism has been implicated in the
      pathomechanism of stroke, myocardial ischemia, diabetes, diabetes-associated
      cardiovascular dysfunction, shock, traumatic central nervous system injury,
      arthritis, colitis, allergic encephalomyelitis, and various other forms of
      inflammation. PARP has also been shown to associate with and regulate the
      function of several transcription factors. Of special interest is the enhancement
      by PARP of nuclear factor kappa B-mediated transcription, which plays a central
      role in the expression of inflammatory cytokines, chemokines, adhesion molecules,
      and inflammatory mediators. Herein we review the double-edged sword roles of PARP
      in DNA damage signaling and cell death and summarize the underlying mechanisms of
      the anti-inflammatory effects of PARP inhibitors. Moreover, we discuss the
      potential use of PARP inhibitors as anticancer agents, radiosensitizers, and
      antiviral agents.

PMID- 12223531
TI  - Caveolae: from cell biology to animal physiology.
AB  - Among the membrane compartments of a cell, vesicles known as "caveolae" have long
      defied functional characterization. However, since the identification of a family
      of proteins termed "caveolins", that form and reside in caveolae, a better
      understanding has emerged. It is now clear that caveolae do not merely play a
      singular role in the cell, but are pleiotropic in nature-serving to modulate many
      cellular functions. The purpose of this review is to explicate what is known
      about caveolins/caveolae and highlight growing areas of caveolar research.

PMID- 12223532
TI  - Amyloid precursor protein, presenilins, and alpha-synuclein: molecular
      pathogenesis and pharmacological applications in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common cause of dementia that arises on a
      neuropathological background of amyloid plaques containing beta-amyloid (A beta)
      derived from amyloid precursor protein (APP) and tau-rich neurofibrillary
      tangles. To date, the cause and progression of both familial and sporadic AD have
      not been fully elucidated. The autosomal-dominant inherited forms of early-onset
      Alzheimer's disease are caused by mutations in the genes encoding APP, presenilin
      1 (chromosome 14), and presenilin-2 (chromosome 1). APP is processed by several
      different proteases such as secretases and/or caspases to yield A beta and
      carboxyl-terminal fragments, which have been implicated in the pathogenesis of
      Alzheimer's disease. Alzheimer's disease and Parkinson's disease are associated
      with the cerebral accumulation of A beta and alpha-synuclein, respectively. Some
      patients have clinical and pathological features of both diseases, raising the
      possibility of overlapping pathogenic pathways. Recent studies have strongly
      suggested the possible pathogenic interactions between A beta, presenilins,
      and/or alpha-synuclein. Therefore, treatments that block the accumulation of A
      beta and alpha-synuclein might benefit a broad spectrum of neurodegenerative
      disorders. This review covers the trafficking and processing of APP, amyloid
      cascade hypothesis in AD pathogenesis, physiological and pathological roles of
      presenilins, molecular characteristics of alpha-synuclein, their interactions,
      and therapeutic strategies for AD.

PMID- 12223533
TI  - Cellular regulation of RGS proteins: modulators and integrators of G protein
      signaling.
AB  - Regulators of G protein signaling (RGS) and RGS-like proteins are a family (>30
      members) of highly diverse, multifunctional signaling proteins that bind directly
      to activated G alpha subunits. Family members are defined by a shared RGS domain,
      which is responsible for G alpha binding and markedly stimulates the GTPase
      activity of G alpha subunits leading to their deactivation and termination of
      downstream signals. Although much has been learned in recent years about the
      biochemistry of RGS/G alpha interactions, considerably less is known about the
      broader cellular roles and regulation of RGS proteins. Recent findings indicate
      that cellular mechanisms such as covalent modification, alternative gene
      splicing, and protein processing can dictate the activity and subcellular
      localization of RGS proteins. Many family members also directly link G proteins
      to a growing list of signaling proteins with diverse cellular roles. New findings
      indicate that RGS proteins act not as dedicated inhibitors but, rather, as
      tightly regulated modulators and integrators of G protein signaling. In some
      cases, RGS proteins modulate the lifetime and kinetics of both slow-acting (e.g.,
      Ca(2+) oscillations) and fast-acting (e.g., ion conductances, phototransduction)
      signaling responses. In other cases, RGS proteins integrate G proteins with
      signaling pathways linked to such diverse cellular responses as cell growth and
      differentiation, cell motility, and intracellular trafficking. These and other
      recent studies with animal model systems indicate that RGS proteins play
      important roles in both physiology and disease. Recognition of the central
      functions these proteins play in vital cellular processes has focused our
      attention on RGS proteins as exciting new candidates for therapeutic intervention
      and drug development.

PMID- 12223534
TI  - Selective action of orexin (hypocretin) on nonspecific thalamocortical projection
      neurons.
AB  - As is evident from the pathological consequences of its absence in narcolepsy,
      orexin (hypocretin) appears to be critical for the maintenance of wakefulness.
      Via diffuse projections through the brain, orexin-containing neurons in the
      hypothalamus may act on a number of wake-promoting systems. Among these are the
      intralaminar and midline thalamic nuclei, which project in turn in a widespread
      manner to the cerebral cortex within the nonspecific thalamocortical projection
      system. Testing the effect of orexin in rat brain slices, in two nuclei of this
      system, centromedial (CM) nuclei and rhomboid nuclei, we found that it
      depolarized and excited all neurons tested through a direct postsynaptic action.
      An additional analysis of this effect in CM neurons indicates that it results
      from the decrease of a potassium conductance. By a detailed comparison of the
      effects of orexin A and B, we established that orexin B was more potent than
      orexin A, indicating the probable mediation by orexin type 2 receptors. In
      contrast to its effect on the nonspecific thalamocortical projection neurons,
      orexin had no effect on the specific sensory relay neurons of the somatic,
      ventral posterolateral, and visual dorsal lateral geniculate nuclei. Orexin
      differs in this regard from norepinephrine and acetylcholine, to which neurons in
      the specific and nonspecific systems are sensitive. Orexin may thus act in the
      thalamus to promote wakefulness by exciting neurons of the nonspecific
      thalamocortical projection system, which, through widespread projections to the
      cerebral cortex, stimulate and maintain cortical activation.

PMID- 12223535
TI  - Environmental enrichment reverses the effects of maternal separation on stress
      reactivity.
AB  - Postnatal maternal separation increases hypothalamic corticotropin-releasing
      factor (CRF) gene expression and hypothalamic-pituitary-adrenal (HPA) and
      behavioral responses to stress. We report here that environmental enrichment
      during the peripubertal period completely reverses the effects of maternal
      separation on both HPA and behavioral responses to stress, with no effect on CRF
      mRNA expression. We conclude that environmental enrichment leads to a functional
      reversal of the effects of maternal separation through compensation for, rather
      than reversal of, the neural effects of early life adversity.

PMID- 12223536
TI  - The role of corticotropin-releasing factor in the median raphe nucleus in relapse
      to alcohol.
AB  - Using an animal model of drug relapse, we found that intermittent footshock
      stress reinstates alcohol seeking, an effect attenuated by the 5-HT reuptake
      blocker fluoxetine and by corticotropin-releasing factor (CRF) receptor
      antagonists. Here we studied the role of the 5-HT cell body region of the median
      raphe nucleus (MRN) and CRF receptors in this site in reinstatement of alcohol
      seeking. Rats were given alcohol in a two-bottle choice procedure (water vs
      alcohol) for 25 d and were then trained for 1 hr/d to press a lever for alcohol
      (12% w/v) for 23-30 d. Subsequently, lever pressing for alcohol was extinguished
      by terminating drug delivery for 5-9 d. Tests for reinstatement of alcohol
      seeking were then performed under extinction conditions. Intra-MRN infusions of 8
      OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] (a 5-HT1A agonist that decreases
      5-HT cell firing and release) reinstated alcohol seeking. Reinstatement of
      alcohol seeking also was observed after intra-MRN infusions of low doses of CRF
      (3-10 ng), which mimicked the effect of ventricular infusions of higher doses of
      the peptide (300-1000 ng). Finally, intra-MRN infusions of the CRF receptor
      antagonist d-Phe CRF (50 ng) blocked the effect of intermittent footshock (10
      min) on reinstatement. These data suggest that an interaction between CRF and 5
      HT neurons within the MRN is involved in footshock stress-induced reinstatement
      of alcohol seeking.

PMID- 12223537
TI  - Dopamine replacement therapy reverses abnormal synchronization of pallidal
      neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of
      parkinsonism.
AB  - Previous physiological studies have revealed changes in firing rates and
      synchronization of pallidal neurons in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) primate model of Parkinson's disease. Several primate
      and human studies have demonstrated that dopamine replacement therapy (DRT)
      reverses the changes in the pallidal firing rates; however, the effects of DRT on
      pallidal synchronization have never been explored. To do so, we recorded the
      simultaneous activity of pallidal neurons of a vervet monkey before and after
      induction of severe parkinsonism by systemic MPTP treatment. We subsequently
      recorded the pallidal activity before and after daily administration of oral DRT.
      We extended the time scale of our correlation studies to +/-5 sec to allow
      detection of long-duration synchronized neuronal activity. After MPTP treatment,
      firing rates decreased in the external segment of the globus pallidus (GP(e)) and
      increased in the internal segment (GP(i)). A reversal of these rate changes
      occurred during the "on" periods of DRT. The percentage of correlated pairs
      increased from 16.7% in the normal state to 46.9% after MPTP treatment and was
      restored to nearly normal values (25% correlated pairs) under the influence of
      DRT. These changes in rate and correlation were observed at both the population
      level and at the level of units recorded continuously before, during, and after
      the clinical transition from "off" to "on" periods. We conclude that changes in
      both pallidal discharge rates and synchronization are correlated with the
      clinical manifestations of parkinsonism and its pharmacological treatment.

PMID- 12223538
TI  - Additive effect of stress and drug cues on reinstatement of ethanol seeking:
      exacerbation by history of dependence and role of concurrent activation of
      corticotropin-releasing factor and opioid mechanisms.
AB  - Stress and exposure to drug-related environmental stimuli have been implicated as
      critical factors in relapse to drug use. What has received little attention,
      however, is the significance of interactions between these factors for motivating
      drug-seeking behavior. To address this issue, a reinstatement model of relapse
      was used. Footshock stress and response-contingent presentation of an ethanol
      associated light cue, acting as a conditioned stimulus (CS), effectively
      reinstated extinguished responding at a previously active, drug-paired lever in
      male Wistar rats. When response-contingent availability of the ethanol CS was
      preceded by footshock, additive effects of these stimuli on responding were
      observed. Both the individual and interactive effects of footshock and the CS
      were significantly greater in previously ethanol-dependent than in nondependent
      rats. Responding induced by the ethanol CS was selectively reversed by the
      nonselective opiate antagonist naltrexone, whereas the effects of footshock were
      selectively reversed by the corticotropin-releasing factor (CRF) antagonist d-Phe
      CRF(12-41). However, both agents only partially reversed the enhanced drug
      seeking response produced by the interactive effects of stress and the ethanol
      CS; full reversal required coadministration of d-Phe-CRF and naltrexone. The
      results document that stress and drug-related environmental stimuli interact to
      augment the resumption of drug seeking after extinction and suggest that this
      effect results from concurrent activation of opioid and CRF transmission.

PMID- 12223539
TI  - Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington's
      disease.
AB  - Huntington's disease (HD) results from polyglutamine expansion in huntingtin
      (htt), a protein with several consensus caspase cleavage sites. Despite the
      identification of htt fragments in the brain, it has not been shown conclusively
      that htt is cleaved by caspases in vivo. Furthermore, no study has addressed when
      htt cleavage occurs with respect to the onset of neurodegeneration. Using
      antibodies that detect only caspase-cleaved htt, we demonstrate that htt is
      cleaved in vivo specifically at the caspase consensus site at amino acid 552. We
      detect caspase-cleaved htt in control human brain as well as in HD brains with
      early grade neuropathology, including one homozygote. Cleaved htt is also seen in
      wild-type and HD transgenic mouse brains before the onset of neurodegeneration.
      These results suggest that caspase cleavage of htt may be a normal physiological
      event. However, in HD, cleavage of mutant htt would release N-terminal fragments
      with the potential for increased toxicity and accumulation caused by the presence
      of the expanded polyglutamine tract. Furthermore, htt fragments were detected
      most abundantly in cortical projection neurons, suggesting that accumulation of
      expanded htt fragments in these neurons may lead to corticostriatal dysfunction
      as an early event in the pathogenesis of HD.

PMID- 12223540
TI  - Non-Fc-mediated mechanisms are involved in clearance of amyloid-beta in vivo by
      immunotherapy.
AB  - Transgenic (Tg) mouse models overexpressing amyloid precursor protein (APP)
      develop senile plaques similar to those found in Alzheimer's disease in an age
      dependent manner. Recent reports demonstrated that immunotherapy is effective at
      preventing or removing amyloid-beta deposits in the mouse models. To characterize
      the mechanisms involved in clearance, we used antibodies of either IgG1 (10d5) or
      IgG2b (3d6) applied directly to the brains of 18-month-old Tg2576 or 20-month-old
      PDAPP mice. Both 10d5 and 3d6 led to clearance of 50% of diffuse amyloid deposits
      in both animal models within 3 d. Fc receptor-mediated clearance has been shown
      to be important in an ex vivo assay showing antibody-mediated clearance of
      plaques by microglia. We now show, using in vivo multiphoton microscopy, that
      FITC-labeled F(ab')2 fragments of 3d6 (which lack the Fc region of the antibody)
      also led to clearance of 45% of the deposits within 3 d, similar to the results
      obtained with full-length 3d6 antibody. This result suggests that direct
      disruption of plaques, in addition to Fc-dependent phagocytosis, is involved in
      the antibody-mediated clearance of amyloid-beta deposits in vivo. Dense-core
      deposits that were not cleared were reduced in size by approximately 30% with
      full-length antibodies and F(ab')2 fragments 3 d after a topical treatment.
      Together, these results indicate that clearance of amyloid deposits in vivo may
      involve, in addition to Fc-dependent clearance, a non-Fc-mediated disruption of
      plaque structure.

PMID- 12223541
TI  - The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha
      subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a
      calcium-dependent manner.
AB  - Cyclin-dependent kinase 5 (Cdk5) is a critical regulator of neuronal migration in
      the developing CNS, and recent studies have revealed a role for Cdk5 in
      synaptogenesis and regulation of synaptic transmission. Deregulation of Cdk5 has
      been linked to the pathology of neurodegenerative diseases such as Alzheimer's
      disease. Activation of Cdk5 requires its association with a regulatory subunit,
      and two Cdk5 activators, p35 and p39, have been identified. To gain further
      insight into the functions of Cdk5, we identified proteins that interact with p39
      in a yeast two-hybrid screen. In this study we report that alpha-actinin-1 and
      the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II (CaMKIIalpha),
      two proteins localized at the postsynaptic density, interact with Cdk5 via their
      association with p35 and p39. CaMKIIalpha and alpha-actinin-1 bind to distinct
      regions of p35 and p39 and also can interact with each other. The association of
      CaMKIIalpha and alpha-actinin-1 to the Cdk5 activators, as well as to each other,
      is stimulated by calcium. Further, the activation of glutamate receptors
      increases the association of p35 and p39 with CaMKIIalpha, and the inhibition of
      CaMKII activation diminishes this effect. The glutamate-mediated increase in
      association of p35 and CaMKIIalpha is mediated in large part by NMDA receptors,
      suggesting that cross talk between the Cdk5 and CaMKII signal transduction
      pathways may be a component of the complex molecular mechanisms contributing to
      synaptic plasticity, memory, and learning.

PMID- 12223542
TI  - Regulation of synaptic plasticity genes during consolidation of fear
      conditioning.
AB  - In mammals, long-term memory induced by Pavlovian fear conditioning has been
      shown to be dependent on the amygdala during a protein and mRNA synthesis
      dependent phase of memory consolidation. We have used genes identified in a
      kainic acid model of synaptic plasticity as in situ hybridization probes during
      the consolidation period after fear conditioning. We found that these genes were
      transcriptionally regulated in several brain areas only when stimuli were
      presented in a manner that supported behavioral learning and not after unpaired
      presentations or footshocks alone. Immediate early genes and neurofilament mRNA
      peaked approximately 30 min after conditioning, as expected. Interestingly, nurr
      1, alpha-actinin, and 16c8 increased approximately 2-4 hr later, whereas
      neurogranin and gephyrin decreased during that time. Our results suggest that
      fear memory consolidation occurs within a broad neural circuit that includes, but
      is not limited to, the amygdala. Together, a broad array of transcriptionally
      regulated genes, encoding transcription factors, cytoskeletal proteins, adhesion
      molecules, and receptor stabilization molecules, appear to mediate the neural
      plasticity underlying specific forms of long-term memory in mammals.

PMID- 12223543
TI  - Nicotinic alpha 7 receptor clusters on hippocampal GABAergic neurons: regulation
      by synaptic activity and neurotrophins.
AB  - Nicotinic acetylcholine receptors containing the alpha7 gene product are
      expressed at substantial levels in the hippocampus. Because of their specific
      locations and their high relative calcium permeability, the receptors not only
      mediate cholinergic transmission in the hippocampus but also influence signaling
      at noncholinergic synapses. We have used fluorescently labeled alpha-bungarotoxin
      to image alpha7-containing receptors on hippocampal neurons and to examine their
      regulation in culture. The highest levels of staining for such receptors were
      most commonly found on GABAergic interneurons identified immunohistochemically.
      The receptors were distributed in clusters on the soma and dendrites and were
      localized in part at GABAergic synapses. A 3 d blockade of electrical activity
      with tetrodotoxin or NMDA receptors with APV dramatically reduced the proportion
      of GABAergic neurons expressing high levels of receptor staining and reduced the
      mean number of distinguishable receptor clusters on individual neurons. Blockade
      of either GABA(A) receptors with bicuculline or nicotinic receptors with d
      tubocurarine had no effect, although exposure to nicotine could increase the
      level of receptor staining. Anti-BDNF and anti-NGF antibodies produced decrements
      equivalent to those of tetrodotoxin and APV, whereas addition of BDNF and NGF
      each increased staining levels and increased the number of distinguishable
      receptor clusters on GABAergic neurons. The exogenous neurotrophins could not,
      however, overcome the effects of either tetrodotoxin or APV. The results indicate
      that both NMDA receptor activation and the neurotrophins BDNF and NGF are
      necessary to sustain the distribution patterns of alpha7-containing nicotinic
      receptors on GABAergic hippocampal neurons.

PMID- 12223544
TI  - Phosphorylation-dependent and phosphorylation-independent modes of modulation of
      shaker family voltage-gated potassium channels by SRC family protein tyrosine
      kinases.
AB  - Modulation of voltage-gated potassium (Kv) channels by protein phosphorylation
      plays an essential role in the regulation of the membrane properties of cells.
      Protein-protein binding domains, such as Src homology 3 (SH3) domains, direct ion
      channel modulation by coupling the channels with intracellular signaling enzymes.
      The conventional view is that protein kinase binding to ion channels leads to
      modulation by bringing the channel substrate into physical proximity to the
      enzyme, thereby fostering covalent modification of the channel. The SH3 domain
      binding-dependent functional suppression of Kv1.5 currents by Src family protein
      tyrosine kinases (PTKs) is considered a canonical example of this type of
      mechanism. In the present study we address whether the SH3-dependent binding of
      Src family PTKs to Shaker family Kvs mediates modulatory events that are
      independent of and/or dependent on Src-catalyzed tyrosine phosphorylation of the
      channel. We find that Src binding and tyrosine phosphorylation are each able to
      modulate Kv1 family macroscopic channel currents independently. SH3-dependent
      binding of Src leads to the suppression of both Kv1.5 and Kv1.4 (modified to
      contain proline-rich SH3 domain binding sites) macroscopic currents even in the
      absence of Src-catalyzed tyrosine phosphorylation, whereas binding-independent
      tyrosine phosphorylation by Src leads to the suppression of Kv1.5 macroscopic
      currents and the modulation of Kv1.4 inactivation kinetics.

PMID- 12223545
TI  - Copper/zinc superoxide dismutase attenuates neuronal cell death by preventing
      extracellular signal-regulated kinase activation after transient focal cerebral
      ischemia in mice.
AB  - Recent studies have revealed that activation of extracellular signal-regulated
      kinase (ERK) may contribute to apoptosis, a cell death process involved in
      oxidative stress. We examined phosphorylation of ERK1/2 and oxidative stress
      after transient focal cerebral ischemia (FCI) using transgenic (Tg) mice that
      overexpress copper/zinc superoxide dismutase (SOD1). The mice were subjected to
      60 min of middle cerebral artery (MCA) occlusion by intraluminal suture blockade
      followed by 1, 4, and 24 hr of reperfusion. Immunohistochemistry and Western blot
      analysis showed that phospho-ERK1 was markedly increased in the cortex within the
      MCA territory at 1 hr of reperfusion (p < 0.01), followed by a decrease at 24 hr
      in wild-type mice. Double staining with phospho-ERK1/2 and neuron-specific
      nuclear protein showed that phospho-ERK1/2 was primarily expressed in neurons. In
      SOD1 Tg mice, phospho-ERK1/2 was prominently reduced compared with nonischemic
      controls, shown by immunohistochemistry. Western blot analysis confirmed a
      significant decrease in phospho-ERK1/2 1 hr after FCI in the ischemic cortex (p <
      0.005). Apoptotic-related DNA fragmentation was reduced in the ischemic cortex of
      SOD1 Tg mice compared with wild-type mice using a cell death assay. These results
      suggest that phosphorylation of ERK1/2 may be involved in apoptosis or cell death
      after transient FCI and that SOD1 may attenuate apoptotic cell death mediated by
      the mitogen-activated protein kinase/ERK pathway.

PMID- 12223546
TI  - Impaired D2 dopamine receptor function in mice lacking type 5 adenylyl cyclase.
AB  - Dopamine receptor subtypes D1 and D2, and many other seven-transmembrane
      receptors including adenosine receptor A2A, are colocalized in striatum of brain.
      These receptors stimulate or inhibit adenylyl cyclases (ACs) to produce distinct
      physiological and pharmacological responses and interact with each other
      synergistically or antagonistically at various levels. The identity of the AC
      isoform that is coupled to each of these receptors, however, remains unknown. To
      investigate the in vivo role of the type 5 adenylyl cyclase (AC5), which is
      preferentially expressed in striatum, mice deficient for the AC5 gene were
      generated. The genetic ablation of the AC5 gene eliminated >80% of forskolin
      induced AC activity and 85-90% of AC activity stimulated by either D1 or A2A
      receptor agonists in striatum. However, D1- or A2A-specific pharmaco-behaviors
      were basically preserved, whereas the signal cascade from D2 to AC was completely
      abolished in AC5(-/-), and motor activity of AC5(-/-) was not suppressed by
      treatment of cataleptic doses of the antipsychotic drugs haloperidol and
      sulpiride. Interestingly, both haloperidol and clozapine at low doses remarkably
      increased the locomotion of AC5(-/-) in the open field test that was produced in
      part by a common mechanism that involved the increased activation of D1 dopamine
      receptors. Together, these results suggest that AC5 is the principal AC
      integrating signals from multiple receptors including D1, D2, and A2A in striatum
      and the cascade involving AC5 among diverse D2 signaling pathways is essential
      for neuroleptic effects of antipsychotic drugs.

PMID- 12223547
TI  - A novel signaling pathway of nitric oxide on transcriptional regulation of mouse
      kappa opioid receptor gene.
AB  - Nitric oxide (NO) suppressed the transcription of the mouse kappa opioid receptor
      (KOR) gene, mediated by a rapid downregulation of c-myc gene expression. KOR was
      constitutively expressed in postnatal day 19 (P19) embryonal carcinoma stem cells
      and is suppressed by NO donors [sodium nitroprusside (SNP), 3
      morpholinosydnonimine-1, and S-nitrosoglutathione] in P19 stem cells within 4 hr.
      The suppression was reversed by 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3
      oxide, an NO scavenger, but could not be blocked by dithiothreitol, ruling out S
      nitrosylation as the underlying mechanism. The suppressive effect of NO on KOR
      occurred at the level of gene transcription, mediated by E boxes located in
      promoters I and II of this gene. Protein-DNA complexes that formed on these E
      boxes contained c-myc; c-myc expression was suppressed by NO in P19 stem cells
      within 2 hr of treatment. Furthermore, chromatin immunoprecipitation demonstrated
      reduced c-myc binding to the E boxes and hypoacetylation of histone H3 on the
      chromatin of endogenous KOR promoters in P19 stem cells treated with SNP. It is
      proposed that NO regulates KOR at the level of gene transcription, mediated by a
      rapid suppression of c-myc gene expression and its binding to KOR promoters, and
      followed by chromatin hypoacetylation of and reduced transcription from KOR
      promoters in P19 stem cells. A novel pathway mediating the potential interplay
      between NO and opioid systems is discussed.

PMID- 12223548
TI  - A new activity of doublecortin in recognition of the phospho-FIGQY tyrosine in
      the cytoplasmic domain of neurofascin.
AB  - Doublecortin is a cytoplasmic protein mutated in the neuronal migration disorder
      X-linked lissencephaly. This study describes a novel activity of doublecortin in
      recognition of the FIGQY-phosphotyrosine motif present in the cytoplasmic domain
      of the L1 cell adhesion molecule neurofascin. Phospho-FIGQY-neurofascin (186 kDa)
      coimmunoprecipitated with doublecortin from detergent extracts of embryonic brain
      membranes, and this doublecortin-phospho-FIGQY neurofascin complex was
      disassociated by a synthetic phospho-FIGQY neurofascin peptide but not by a
      dephospho-FIGQY peptide. Doublecortin specifically recognized the phospho-FIGQY
      tyrosine in the context of a synthetic phospho-FIGQY neurofascin peptide and in
      phospho-FIGQY neurofascin isolated from cells treated with pervanadate. Mutations
      of doublecortin causing lissencephaly (R59H, D62N, and G253D) abolished binding
      to the phospho-FIGQY peptide and to phospho-FIGQY neurofascin. Finally, phospho
      FIGQY neurofascin and doublecortin colocalize in developing axon tracts and in
      zones enriched in migrating neurons in the embryonic cerebral cortex. In the
      adult rostral migratory stream, doublecortin colocalizes in migrating neurons
      with a phospho-FIGQY bearing L1 CAM different from neurofascin. The finding that
      doublecortin associates with FIGQY-phosphorylated neurofascin provides the first
      connection of doublecortin with the plasma membrane and could be important for a
      function of doublecortin in directing neuronal migration.

PMID- 12223549
TI  - Intron 1 is required for cell type-specific, but not injury-responsive,
      peripherin gene expression.
AB  - The "primitive" neurons of the peripheral nervous system (PNS) have the
      remarkable ability to regenerate new fibers. This regenerative process requires a
      sequence of gene activation and repression that is poorly understood. One gene
      that is almost exclusively expressed in neurons of the PNS and is activated after
      nerve injury is the peripherin intermediate filament gene, but little is known
      about the genomic elements that control either its restricted expression or its
      response to nerve injury in adult mice. Previous studies suggested that both 5'
      flanking sequence and intragenic regions were required for cell type-specific and
      injury-specific expression. To determine which intragenic regions were critical,
      mice were generated that expressed peripherin transgenes lacking different
      introns. Analyses of these mice revealed that deletion of introns 2-8 had no
      effect on either the cell type-specific or injury-specific expression of the
      peripherin gene; however, the remaining intron, intron 1, differentially bound
      Sp1 transcription-related proteins/protein complexes in extracts from peripherin
      expressing and nonexpressing tissues. Furthermore, a transgene that lacked intron
      1 was not expressed in many neurons that contain endogenous peripherin but was
      activated after injury. Thus, accurate cell type-specific peripherin gene
      expression in the PNS depends on elements within intron 1, but other sequences,
      most likely in the 5'flanking region, are required for activating the peripherin
      gene in response to nerve injury.

PMID- 12223550
TI  - Rac GTPase plays an essential role in exocytosis by controlling the fusion
      competence of release sites.
AB  - The role of small GTPases of the Rho family in synaptic functions has been
      addressed by analyzing the effects of lethal toxin (LT) from Clostridium
      sordellii strain IP82 (LT82) on neurotransmitter release at evoked identified
      synapses in the buccal ganglion of Aplysia. LT82 is a large
      monoglucosyltranferase that uses UDP-glucose as cofactor and glucosylates Rac (a
      small GTPase related to Rho), and Ras, Ral, and Rap (three GTPases of the Ras
      family). Intraneuronal application of LT (50 nm) rapidly inhibits evoked
      acetylcholine (ACh) release as monitored electrophysiologically. Injection of the
      catalytic domain of the toxin similarly blocked ACh release, but not when key
      amino acids needed for glucosylation were mutated. Intraneuronal application of
      competitive nucleotide sugars that differentially prevent glucosylation of Rac-
      and Ras-related GTPases, and the use of a toxin variant that affects a different
      spectrum of small GTPases, established that glucosylation of Rac is responsible
      for the reduction in ACh release. To determine the quantal release parameters
      affected by Rac glucosylation, we developed a nonstationary analysis of the
      fluctuations in postsynaptic response amplitudes that was performed before and
      after the toxin had acted or during toxin action. The results indicate that
      neither the quantal size nor the average probability for release were affected by
      lethal toxin action. ACh release blockage by LT82 was only caused by a reduction
      in the number of functional release sites. This reveals that after docking of
      synaptic vesicles, vesicular Rac stimulates a membrane effector (or effectors)
      essential for the fusion competence of the exocytotic sites.

PMID- 12223551
TI  - Desensitization mechanism of GABA receptors revealed by single oocyte binding and
      receptor function.
AB  - Prolonged exposure of most fast neurotransmitter-operated ion channels to agonist
      drives the receptors into a nonfunctional, or desensitized, state. Despite
      extensive investigation, desensitization remains a thoroughly characterized, yet
      poorly understood, process. Part of the difficulty in elucidating the mechanism
      of desensitization has been an inability to resolve the kinetics of both agonist
      binding and functional desensitization in the same set of operable receptors. To
      overcome this limitation, we applied single oocyte 3H-ligand binding and two
      electrode voltage clamp to oocytes expressing recombinant alpha1beta2gamma2 GABA
      receptors. Using this approach, we report several observations fundamental to the
      mechanism of desensitization. First, we confirm that desensitization reversibly
      shifts GABA receptors into a high-affinity state. For [3H]GABA binding, the half
      maximal binding of the desensitized state was approximately 0.040 microm. Second,
      we show that, upon agonist removal, this high-affinity state disappears with a
      time constant of 127 +/- 12 sec (n = 4), similar to the time constant for
      functional recovery from desensitization of 124 +/- 26 sec (n = 5). [3H]GABA,
      however, dissociates fourfold faster (tau = 30 +/- 2 sec; n = 3) than functional
      recovery, indicating that desensitized receptors need not be bound by GABA. These
      data provide direct evidence for a cyclical model of receptor desensitization.

PMID- 12223552
TI  - Calmodulin is an auxiliary subunit of KCNQ2/3 potassium channels.
AB  - Calmodulin (CaM) was identified as a KCNQ2 and KCNQ3 potassium channel-binding
      protein, using a yeast two-hybrid screen. CaM is tethered constitutively to the
      channel, in the absence or presence of Ca2+, in transfected cells and also
      coimmunoprecipitates with KCNQ2/3 from mouse brain. The structural elements
      critical for CaM binding to KCNQ2 lie in two conserved motifs in the proximal
      half of the channel C-terminal domain. Truncations and point mutations in these
      two motifs disrupt the interaction. The first CaM-binding motif has a sequence
      that conforms partially to the consensus IQ motif, but both wild-type CaM and a
      Ca2+-insensitive CaM mutant bind to KCNQ2. The voltage-dependent activation of
      the KCNQ2/3 channel also shows no Ca2+ sensitivity, nor is it affected by
      overexpression of the Ca2+-insensitive CaM mutant. On the other hand, KCNQ2
      mutants deficient in CaM binding are unable to generate detectable currents when
      coexpressed with KCNQ3 in CHO cells, although they are expressed and targeted to
      the cell membrane and retain the ability to assemble with KCNQ3. A fusion protein
      containing both of the KCNQ2 CaM-binding motifs competes with the full-length
      KCNQ2 channel for CaM binding and decreases KCNQ2/3 current density in CHO cells.
      The correlation of CaM binding with channel function suggests that CaM is an
      auxiliary subunit of the KCNQ2/3 channel.

PMID- 12223553
TI  - Altered dopamine release and uptake kinetics in mice lacking D2 receptors.
AB  - Dysregulation of dopamine transmission is thought to contribute to schizophrenic
      psychosis and drug dependence. Dopamine release is regulated by D2 dopamine
      autoreceptors, and D2 receptor ligands are used to treat psychosis and addiction.
      To elucidate the long-term effects of D2 autoreceptor activity on dopamine
      signaling, dopamine overflow evoked by single or paired-pulse stimulation was
      compared in striatal slices from D2-null mutant and wild-type mice. Quinpirole, a
      D2/D3 receptor agonist, had no effect on evoked dopamine release in D2 mutant
      mice, indicating that D2 receptors are the only release-regulating receptors at
      the axon terminal. Dopamine release inhibition by GABA(B) receptor activation was
      unchanged in D2 mutant mice, suggesting that other G-protein-coupled pathways
      remained normal in the absence of D2 autoreceptors. Paired-pulse stimulation
      revealed that autoinhibition of dopamine release was maximal 500 msec after
      stimulation and lasted <5 sec. In D2-null mutants, dopamine overflow in response
      to single stimuli was severely decreased. Experiments with the uptake inhibitor
      nomifensine indicated that this was caused by enhanced dopamine uptake rather
      than reduced release. Analysis of dopamine overflow kinetics using a simulation
      model suggested that the enhanced uptake was caused by an increase in the maximal
      velocity of uptake, V(max). These results from D2-null mutant mice support the
      suggestion that D2 autoreceptors and dopamine transporters interact to regulate
      the amplitude and timing of dopamine signals.

PMID- 12223554
TI  - Kainate receptor subunits underlying presynaptic regulation of transmitter
      release in the dorsal horn.
AB  - Presynaptic kainate (KA) receptors regulate synaptic transmission at both
      excitatory and inhibitory synapses in the spinal cord dorsal horn. Previous work
      has demonstrated pharmacological differences between the KA receptors expressed
      by rat dorsal horn neurons and those expressed by the primary afferent sensory
      neurons that innervate the dorsal horn. Here, neurons isolated from KA receptor
      subunit-deficient mice were used to evaluate the contribution of glutamate
      receptor subunit 5 (GluR5) and GluR6 to the presynaptic control of transmitter
      release and to KA receptor-mediated whole-cell currents in these two cell
      populations [corrected]. Deletion of GluR6 produced a significant reduction in KA
      receptor-mediated current density in dorsal horn neurons, whereas GluR5 deletion
      caused no change in current density but removed sensitivity to GluR5-selective
      antagonists. Presynaptic modulation of inhibitory transmission between dorsal
      horn neurons was preserved in cells from either GluR5- or GluR6-deficient mice.
      In DRG neurons, in contrast, GluR5 deletion abolished KA receptor function,
      whereas deletion of GluR6 had little effect on peak current density but increased
      the rate and extent of desensitization. These results highlight fundamental
      differences in KA receptor physiology between the two cell types and suggest
      possible strategies for the pharmacological modulation of nociception.

PMID- 12223555
TI  - Exogenous smac induces competence and permits caspase activation in sympathetic
      neurons.
AB  - Sympathetic neuronal apoptosis after nerve growth factor (NGF) deprivation
      requires the activation of two events: a protein synthesis-dependent, Bax
      dependent release of mitochondrial cytochrome c and a protein synthesis
      independent, Bax-independent development of competence. Unlike in most cells,
      cytosolic cytochrome c is not sufficient to induce cell death in NGF-maintained
      sympathetic neurons but can do so in neurons that have developed competence. We
      report that cytosolic cytochrome c-induced apoptosis in competent sympathetic
      neurons is completely dependent on caspase-9. In addition, the neuroprotective
      agents KCl and chlorophenylthio-cAMP are potent inhibitors of the development-of
      competence pathway in NGF-deprived sympathetic neurons. We also find that the
      development of competence is reversible. Readdition of NGF reverses competence,
      and neurons can regain their resistance to cytosolic cytochrome c. Importantly,
      we examined the mechanism of development of competence and report that the
      inability of cytochrome c to activate caspases in NGF-maintained sympathetic
      neurons can be overcome with exogenous Smac that inhibits the inhibitor of
      apoptosis (IAP) family of proteins. Microinjection of cytochrome c and Smac, but
      neither alone, induces rapid cell death in NGF-maintained neurons. These data
      suggest that development of competence may be the result of the loss of the
      function of one or more members of the IAP family of caspase inhibitors that is
      needed before cytochrome c can activate caspases and induce cell death in
      neurons.

PMID- 12223556
TI  - Distribution of cystine/glutamate exchange transporter, system x(c)-, in the
      mouse brain.
AB  - Mammalian cells express a transport system known as system x(c)-, which is an
      exchange agency specific for anionic forms of cystine and glutamate. System x(c)-
      activity is important to maintain both intracellular glutathione levels and the
      redox balance between cystine and cysteine in the extracellular milieu. We have
      shown that the cloned cDNAs encoding the transporter for system x(c)- consist of
      two components, xCT and the heavy chain of 4F2 antigen. In the present study, we
      have investigated the mRNA distribution for these components in the mouse brain
      by in situ hybridization. The xCT mRNA was expressed in the area postrema,
      subfornical organ, habenular nucleus, hypothalamic area, and ependymal cells of
      the lateral wall of the third ventricle in the adult mouse brain. A strong signal
      was also detected in the meninges in both adult and fetal mouse brains. The mRNA
      expression of the heavy chain of 4F2 antigen was detected in a more broad area,
      including all of the regions in which xCT mRNA was detected. These data are
      compatible with our biochemical evidence that xCT functions in combination with
      the heavy chain of 4F2 antigen to elicit system x(c)- activity. The expression of
      system x(c)- in meninges and some circumventricular organs may suggest that this
      transporter contributes to the maintenance of the redox state (i.e.,
      cysteine/cystine ratio) in the CSF.

PMID- 12223557
TI  - The role of interleukin-1, interleukin-6, and glia in inducing growth of neuronal
      terminal arbors in mice.
AB  - After injury to the substantia nigra pars compacta (SNpc), remaining neurons
      sprout to ensure normal dopamine delivery to the striatum. The consequent
      striatal reinnervation is highly regulated, with remaining cells sprouting so
      that density of dopamine terminals returns to normal. Sprouting as a result of
      injury is accompanied by a strong glial response; however, it is difficult to
      know whether this response is as a result of the injury or whether it is aiding
      in the sprouting. The two cytokines interleukin-1 (IL-1) and interleukin-6 (IL-6)
      are important modulators of the glia response. This study demonstrates their role
      in regulating the sprouting of dopaminergic neurons and the associated glia
      response as a means to examine the role of glia in sprouting. Sprouting was
      induced by 6-hydroxydopamine lesions of the SNpc and by haloperidol treatment (in
      the absence of injury). In wild-type animals, sprouting in association with
      microglial and astrocyte proliferation followed partial lesions of the SNpc and
      haloperidol treatment. Neither treatment evoked sprouting or glia proliferation
      in the type I IL-1 receptor-deficient mice, whereas in IL-6-deficient mice, both
      treatments resulted in glial proliferation but not sprouting. We conclude that IL
      1 plays a role in modulating glia proliferation and thereby guidance and trophic
      factors for new fibers, whereas IL-6 may be important in triggering the outgrowth
      of new fibers. This study demonstrates that these cytokines play an important
      role in plasticity and regeneration that is separate from the inflammatory
      response associated with brain injury.

PMID- 12223558
TI  - The AMPA receptor subunit GluR1 regulates dendritic architecture of motor
      neurons.
AB  - The morphology of the mature motor neuron dendritic arbor is determined by
      activity-dependent processes occurring during a critical period in early
      postnatal life. The abundance of the AMPA receptor subunit GluR1 in motor neurons
      is very high during this period and subsequently falls to a negligible level. To
      test the role of GluR1 in dendrite morphogenesis, we reintroduced GluR1 into rat
      motor neurons at the end of the critical period and quantitatively studied the
      effects on dendrite architecture. Two versions of GluR1 were studied that
      differed by the amino acid in the "Q/R" editing site. The amino acid occupying
      this site determines single-channel conductance, ionic permeability, and other
      essential electrophysiologic properties of the resulting receptor channels. We
      found large-scale remodeling of dendritic architectures in a manner depending on
      the amino acid occupying the Q/R editing site. Alterations in the distribution of
      dendritic arbor were not prevented by blocking NMDA receptors. These observations
      suggest that the expression of GluR1 in motor neurons modulates a component of
      the molecular substrate of activity-dependent dendrite morphogenesis. The control
      of these events relies on subunit-specific properties of AMPA receptors.

PMID- 12223559
TI  - Distally directed dendrotoxicity induced by kainic Acid in hippocampal
      interneurons of green fluorescent protein-expressing transgenic mice.
AB  - Excitotoxicity, resulting from the excessive release of glutamate, is thought to
      contribute to a variety of neurological disorders, including epilepsy.
      Excitotoxic damage to dendrites, i.e., dendrotoxicity, is often characterized by
      the formation of large dendritic swellings, or "beads." Here, we show that
      hippocampal interneurons that express the neuropeptide somatostatin are highly
      vulnerable to the excitotoxic effects of the ionotropic glutamate receptor
      agonist kainate. Brief, focal iontophoretic application of kainate rapidly
      induced bead formation in dendrites of somatostatinergic interneurons that
      express green fluorescent protein (GFP) from mice of the transgenic line GIN (GFP
      expressing inhibitory neurons). Surprisingly, beads often did not form at the
      site of kainate application or even in the dendritic segment to which kainate was
      applied; instead, dendritic beading occurred more distally, often encompassing
      all branches distal to the application site. We have termed this phenomena,
      "distally directed dendrotoxicity." Distally directed beading was induced
      regardless of the branch order of the site of application and was found to be
      dependent on activation of voltage-gated sodium channels. Subsequent to
      induction, distally directed beading would reverse in most cells; in other cells,
      however, beading irreversibly invaded proximal dendritic segments and gradually
      encompassed the entire dendritic tree. These results demonstrate that distal
      dendritic segments are highly vulnerable to excitotoxic injury and imply that
      excessive excitatory activity originating in one synaptic pathway can impact
      synapses at more distal dendritic segments of the same neuron. The discovery of
      this phenomenon will likely be important in understanding interneuronal
      dysfunction following excitotoxic injury.

PMID- 12223560
TI  - Beta-adrenoceptor agonists stimulate endothelial nitric oxide synthase in rat
      urinary bladder urothelial cells.
AB  - We have investigated the intracellular signaling mechanisms underlying the
      release of nitric oxide (NO) evoked by beta-adrenoceptor (AR) agonists in urinary
      bladder strips and cultured bladder urothelial cells from adult rats. Reverse
      transcription-PCR revealed that inducible NO synthase and endothelial NOS but not
      neuronal NOS genes were expressed in urothelial cells. NO release from both
      urothelial cells and bladder strips was decreased (37-42%) in the absence of
      extracellular Ca2+ (100 microm EGTA) and was ablated after incubation with BAPTA
      AM (5 microm) or caffeine (10 mm), indicating that the NO production is mediated
      in part by intracellular calcium stores. NO release was reduced (18-24%) by
      nifedipine (10 microm) and potentiated (29-32%) by incubation with the Ca2+
      channel opener BAYK8644 (1-10 microm). In addition, beta-AR-evoked NO release
      (isoproterenol; dobutamine; terbutaline; 10(-9) to 10(-5) m) was blocked by the
      NOS inhibitors N(G)-nitro-L-arginine methyl ester (30 microm) or N(G)-monomethyl
      L-arginine (50 microm), by beta-adrenoceptor antagonists (propranol, beta1/beta2;
      atenolol, beta1; ICI 118551; beta2; 100 microm), or by the calmodulin antagonist
      trifluoperazine (50 microm). Incubating cells with the nonhydrolyzable GTP analog
      GTPgammaS (1 microm) or the membrane-permeant cAMP analog dibutyryl-cAMP (10-100
      microm) directly evoked NO release. Forskolin (10 microm) or the
      phosphodiesterase IBMX (50 microm) enhanced (39-42%) agonist-evoked NO release.
      These results indicate that beta-adrenoceptor stimulation activates the adenylate
      cyclase pathway in bladder epithelial cells and initiates an increase in
      intracellular Ca2+ that triggers NO production and release. These findings are
      considered in light of recent reports that urothelial cells may exhibit a number
      of "neuron-like" properties, including the expression of receptors/ion channels
      similar to those found in sensory neurons.

PMID- 12223561
TI  - Three functionally distinct adhesions in filopodia: shaft adhesions control
      lamellar extension.
AB  - In this study, adhesions on individual filopodial shafts were shown to control
      veil (lamellar) advance and to be modulated by guidance cues. Adhesions were
      detected in individual filopodia of sensory growth cones using optical
      recordings, adhesion markers, and electron microscopy. Veils readily advanced
      along filopodia lacking shaft adhesions but rarely advanced along filopodia
      displaying shaft adhesions. Experiments altering adhesion showed that this
      relationship is not caused by veils removing adhesions as they advanced. Reducing
      adhesion with antibodies decreased the proportion of filopodia with shaft
      adhesions and coordinately increased veil advance. Moreover, the inhibitory
      relationship was maintained: veils still failed to advance on individual
      filopodia that retained shaft adhesions. These results support the idea that
      shaft adhesions inhibit veil advance. Of particular interest, guidance cues can
      act by altering shaft adhesions. When a cellular cue was contacted by a
      filopodial tip, veil extension and shaft adhesions altered in concert. Contact
      with a Schwann cell induced veil advance and inhibited shaft adhesions. In
      contrast, contact with a posterior sclerotome cell prohibited veil advance and
      promoted shaft adhesions. These results show that veil advance is controlled by
      shaft adhesions and that guidance signal cascades can alter veil advance by
      altering these adhesions. Shaft adhesions thus differ functionally from two other
      adhesions identified on individual filopodia. Tip adhesions suffice to signal.
      Basal adhesions do not influence veil advance but are critical to filopodial
      initiation and dynamics. Individual growth cone filopodia thus develop three
      functionally distinct adhesions that are vital for both motility and navigation.

PMID- 12223562
TI  - Dark rearing alters the development of GABAergic transmission in visual cortex.
AB  - We studied the role of sensory experience in the maturation of GABAergic circuits
      in the rat visual cortex. Between the time at which the eyes first open and the
      end of the critical period for experience-dependent plasticity, the total
      GABAergic input converging into layer II/III pyramidal cells increases threefold.
      We propose that this increase reflects changes in the number of quanta released
      by presynaptic axons. Here, we show that the developmental increase in GABAergic
      input is prevented in animals deprived of light since birth but not in animals
      deprived of light after a period of normal experience. Thus, sensory experience
      appears to play a permissive role in the maturation of intracortical GABAergic
      circuits.

PMID- 12223563
TI  - Metalloproteases and guidance of retinal axons in the developing visual system.
AB  - Axonal growth cones read cues in their environment that guide them to their
      target. Metalloproteases have been implicated in vitro in modulating the
      interaction of these cues with receptors in the growth cone. To determine whether
      metalloprotease function is important in the guidance of vertebrate axons in
      vivo, we applied hydroxamate-based metalloprotease inhibitors to Xenopus retinal
      ganglion cell (RGC) axons as they extended through the optic tract. In the
      presence of two different inhibitors, 0.5-20 microm N-[(2R)
      2(hydroxamideocarbonylmethyl)-4-methylpantanoyl]-l-tryptophan methylamide and
      batimastat, RGC axons made similar dose-dependent guidance errors. Most axons
      failed to make the expected caudal turn in the diencephalon and continued
      straight, growing aberrantly toward and across the dorsal midline. As a result,
      few RGC axons innervated their midbrain target, the optic tectum. Similarly, if
      the inhibitors were applied after the axons made the turn, many failed to grow
      into the optic tectum and instead turned to grow along its anterior border.
      Interestingly, in many instances pathfinding defects were observed in the absence
      of problems with axon extension, although outgrowth was impaired at the higher
      doses of the inhibitors. These data provide compelling in vivo evidence that
      metalloproteases are important for both axon guidance and extension in the
      developing visual system.

PMID- 12223564
TI  - Extrasynaptic alpha 7-nicotinic acetylcholine receptor expression in developing
      neurons is regulated by inputs, targets, and activity.
AB  - Alpha7-nicotinic acetylcholine receptors (nAChRs) are widely expressed in the
      vertebrate nervous system. alpha7-nAChR functions include postsynaptic
      transmission, modulating neurotransmitter release, reinforcing nicotine
      addiction, and a role in neurological disorders, such as schizophrenia and
      Alzheimer's disease. In chick parasympathetic ciliary ganglion (CG) neurons,
      alpha7-nAChRs are excluded from the synapse and localize perisynaptically.
      Despite their extrasynaptic distribution, the highly Ca2+-permeable alpha7-nAChRs
      have important synapse-related Ca2+-dependent signaling functions in the CG. We
      show here that the synaptic partners regulate alpha7-nAChR expression during
      synapse formation in embryonic CG neurons in situ. The absence of inputs and
      target tissues cause reductions in alpha7-nAChR mRNA and protein levels that
      primarily resemble those seen for synaptic alpha3-nAChRs. However, there is a
      difference in their regulation. alpha7-nAChR levels are downregulated by reduced
      activity, whereas alpha3-nAChR levels are not. We propose that the activity
      dependent regulation of extrasynaptic alpha7-nAChR levels may be an important
      mechanism for postsynaptic CG neurons to detect changes in presynaptic activity
      levels and respond with Ca2+-dependent plasticity changes in gene expression.

PMID- 12223565
TI  - Dissection of the cellular and molecular events that position cerebellar Purkinje
      cells: a study of the math1 null-mutant mouse.
AB  - Granule cell precursors in the external germinal layer (EGL) of the cerebellum
      have been proposed to be a major player in the migration and positioning of
      Purkinje cells through the expression of the Netrin-like receptor Unc5h3 and the
      extracellular matrix molecule Reelin. To explore the role of the EGL on these
      processes, we made use of the math1 null-mutant mouse in which the EGL does not
      form. In the absence of the EGL, we find three populations of ectopic Purkinje
      cells. First, we find 1% of all Purkinje cells in a supracerebellar position at
      the dorsal midline. Second, we find 7% of all Purkinje cells in the inferior
      colliculus, similar to what is seen in the Unc5h3 mutant. Our finding that Unc5h3
      expression is not disrupted in these cells supports the proposed role of EGL
      granule cell precursors in establishing the anterior cerebellar boundary through
      the expression of Unc5h3. Third, we find 20% of all Purkinje cells positioned
      deep to the cerebellar cortex as seen in the reeler mutant. However, unlike the
      reeler mutant, where 5% of the Purkinje cells migrate successfully, we find that
      in the math1 null that 72% of the Purkinje cells migrate successfully. This
      finding demonstrates that Purkinje cell migration is not solely dependent on
      Reelin signaling from the EGL and is likely caused by Reelin signals emanating
      from the nuclear transitory zone or the ventricular zone, or both.

PMID- 12223566
TI  - Thalamic relay nuclei of the basal ganglia form both reciprocal and nonreciprocal
      cortical connections, linking multiple frontal cortical areas.
AB  - Thalamic relay nuclei transmit basal ganglia output to the frontal cortex,
      forming the last link in corticobasal ganglia circuitry. The thalamus regulates
      cortical activity through differential laminar connections, providing not only
      feedback, but also initiating "feedforward" loops, via nonreciprocal projections,
      that influence higher cortical areas. This study examines the organization of
      thalamic connections with cortex from basal ganglia relay nuclei, including
      ventral anterior (VA), ventral lateral (VL), and mediodorsal (MD) nuclei, in the
      Macaque monkey. Anterograde and bidirectional tracer injections ([3H]-amino
      acids, dextran conjugates of Fluorescein, Lucifer Yellow or FluoroRuby, or wheat
      germ agglutinin) into discrete VA/VL, MD, and frontal cortical sites demonstrate
      specific thalamocortical connections. VL projections target caudal motor areas
      (primary, supplementary, and caudal premotor areas), whereas VA projections
      target more rostral premotor areas (including cingulate and presupplementary
      motor areas) and MD projects to dorsolateral and orbital prefrontal cortices.
      Thalamocortical projections innervate cortical layers I and III, and to a lesser
      extent, layer V. In motor areas layer I projections are more extensive than those
      to layer III (and V). The complex laminar organization of projections from
      specific thalamic sites suggests differential regulation of cortical function.
      Injections of bidirectional tracers into thalamic and frontal cortical sites also
      show that in comparison to thalamocortical projections, corticothalamic
      projections to VA-VL and MD are more widespread. These findings demonstrate both
      reciprocal and nonreciprocal components to the thalamo-cortico-thalamic relay.
      Together, these experiments indicate a dual role for VA-VL and MD nuclei: (1) to
      relay basal ganglia output within specific cortical circuits and (2) to mediate
      information flow between cortical circuits.

PMID- 12223567
TI  - Delta FosB regulates wheel running.
AB  - DeltaFosB is a transcription factor that accumulates in a region-specific manner
      in the brain after chronic perturbations. For example, repeated administration of
      drugs of abuse increases levels of DeltaFosB in the striatum. In the present
      study, we analyzed the effect of spontaneous wheel running, as a model for a
      natural rewarding behavior, on levels of DeltaFosB in striatal regions. Moreover,
      mice that inducibly overexpress DeltaFosB in specific subpopulations of striatal
      neurons were used to study the possible role of DeltaFosB on running behavior.
      Lewis rats given ad libitum access to running wheels for 30 d covered what would
      correspond to approximately 10 km/d and showed increased levels of DeltaFosB in
      the nucleus accumbens compared with rats exposed to locked running wheels. Mice
      that overexpress DeltaFosB selectively in striatal dynorphin-containing neurons
      increased their daily running compared with control littermates, whereas mice
      that overexpress DeltaFosB predominantly in striatal enkephalin-containing
      neurons ran considerably less than controls. Data from the present study
      demonstrate that like drugs of abuse, voluntary running increases levels of
      DeltaFosB in brain reward pathways. Furthermore, overexpression of DeltaFosB in a
      distinct striatal output neuronal population increases running behavior. Because
      previous work has shown that DeltaFosB overexpression within this same neuronal
      population increases the rewarding properties of drugs of abuse, results of the
      present study suggest that DeltaFosB may play a key role in controlling both
      natural and drug-induced reward.

PMID- 12223568
TI  - Functional downregulation of P2X3 receptor subunit in rat sensory neurons reveals
      a significant role in chronic neuropathic and inflammatory pain.
AB  - The excitation of nociceptive sensory neurons by ATP released in injured tissue
      is believed to be mediated partly by P2X3 receptors. Although an analysis of P2X3
      knock-out mice has revealed some deficits in nociceptive signaling, detailed
      analysis of the role of these receptors is hampered by the lack of potent
      specific pharmacological tools. Here we have used antisense oligonucleotides
      (ASOs) to downregulate P2X3 receptors to examine their role in models of chronic
      pain in the rat. ASOs and control missense oligonucleotides (180 microg/d) were
      administered intrathecally to naive rats for up to 7 d via a lumbar indwelling
      cannula attached to an osmotic minipump. Functional downregulation of the
      receptors was confirmed by alphabeta-methylene ATP injection into the hindpaw,
      which evoked significantly less mechanical hyperalgesia as early as 2 d after
      treatment with ASOs relative to controls. At this time point, P2X3 protein levels
      were significantly downregulated in lumbar L4 and L5 dorsal root ganglia. After 7
      d of ASO treatment, P2X3 protein levels were reduced in the primary afferent
      terminals in the lumbar dorsal horn of the spinal cord. In models of neuropathic
      (partial sciatic ligation) and inflammatory (complete Freund's adjuvant) pain,
      inhibition of the development of mechanical hyperalgesia as well as significant
      reversal of established hyperalgesia were observed within 2 d of ASO treatment.
      The time course of the reversal of hyperalgesia is consistent with downregulation
      of P2X3 receptor protein and function. This study demonstrates the utility of ASO
      approaches for validating gene targets in in vivo pain models and provides
      evidence for a role of P2X3 receptors in the pathophysiology of chronic pain.

PMID- 12223569
TI  - Chromatic light adaptation measured using functional magnetic resonance imaging.
AB  - Sensitivity changes, beginning at the first stages of visual transduction, permit
      neurons with modest dynamic range to respond to contrast variations across an
      enormous range of mean illumination. We have used functional magnetic resonance
      imaging (fMRI) to investigate how these sensitivity changes are controlled within
      the visual pathways. We measured responses in human visual area V1 to a constant
      amplitude, contrast-reversing probe presented on a range of mean backgrounds. We
      found that signals from probes initiated in the L and M cones were affected by
      backgrounds that changed the mean absorption rates in the L and M cones, but not
      by background changes seen only by the S cones. Similarly, signals from S cone
      initiated probes were altered by background changes in the S cones, but not by
      background changes in the L and M cones. Performance in psychophysical tests
      under similar conditions closely mirrored the changes in V1 fMRI signals. We
      compare our data with simulations of the visual pathway from photon catch rates
      to cortical blood-oxygen level-dependent signals and show that the quantitative
      fMRI signals are consistent with a simple model of mean-field adaptation based on
      Naka-Rushton (Naka and Rushton, 1966) adaptation mechanisms within cone
      photoreceptor classes.

PMID- 12223570
TI  - Synaptic convergence of motor and somatosensory cortical afferents onto GABAergic
      interneurons in the rat striatum.
AB  - Cortical afferents to the basal ganglia, and in particular the corticostriatal
      projections, are critical in the expression of basal ganglia function in health
      and disease. The corticostriatal projections are topographically organized but
      also partially overlap and interdigitate. To determine whether projections from
      distinct cortical areas converge at the level of single interneurons in the
      striatum, double anterograde labeling from the primary motor (M1) and primary
      somatosensory (S1) cortices in the rat, was combined with immunolabeling for
      parvalbumin (PV), to identify one population of striatal GABAergic interneurons.
      Cortical afferents from M1 and S1 gave rise to distinct, but partially
      overlapping, arbors of varicose axons in the striatum. PV-positive neurons were
      often apposed by cortical terminals and, in many instances, apposed by terminals
      from both cortical areas. Frequently, individual cortical axons formed multiple
      varicosities apposed to the same PV-positive neuron. Electron microscopy
      confirmed that the cortical terminals formed asymmetric synapses with the
      dendrites and perikarya of PV-positive neurons as well as unlabelled dendritic
      spines. Correlated light and electron microscopy revealed that individual PV
      positive neurons received synaptic input from axon terminals derived from both
      motor and somatosensory cortices. These results demonstrate that, within areas of
      overlap of functionally distinct projections, there is synaptic convergence at
      the single cell level. Sensorimotor integration in the basal ganglia is thus
      likely to be mediated, at least in part, by striatal GABAergic interneurons.
      Furthermore, our findings suggest that the pattern of innervation of GABAergic
      interneurons by cortical afferents is different from the cortical innervation of
      spiny projection neurons.

PMID- 12223571
TI  - Spinal sensorimotor transformation: relation between cutaneous somatotopy and a
      reflex network.
AB  - The projection of primary afferents onto spinal interneurons constitutes the
      first step in sensorimotor transformations performed by spinal reflex systems.
      Despite extensive studies on spinal somatotopy, uncertainties remain concerning
      the extent and significance of representational overlap and relation to spinal
      reflex circuits. To address these issues, the cutaneous projection from the
      hindpaw and its relation to the topography of lamina V neurons encoding
      withdrawal reflex strength ("reflex encoders") was studied in rats. Thin and
      coarse primary afferent terminations in laminas II and III-IV, respectively, were
      mapped by wheat germ agglutinin-horseradish peroxidase and choleragenoid tracing.
      The functional weights of these projections were characterized by mapping
      nociceptive and tactile field potentials and compared with the topography of
      reflex encoders. Both anatomical and physiological data indicate that thin and
      coarse skin afferent input is spatially congruent in the horizontal plane. The
      representation of the hindpaw in the spinal cord was found to be intricate, with
      a high degree of convergence between the projections from different skin sites.
      "Somatotopic disruptions" such as the representation of central pads medial to
      that of the digits were common. The weight distribution of the cutaneous
      convergence patterns in laminas III-IV was similar to that of lamina V reflex
      encoders. This suggests that the cutaneous convergence and features such as
      somatotopic disruptions have specific relations to the sensorimotor
      transformations performed by reflex interneurons in the deep dorsal horn. Hence,
      the spinal somatotopic map may be better understood in light of the topography of
      such reflex systems.

PMID- 12223572
TI  - Somatotopic activation in the human trigeminal pain pathway.
AB  - Functional magnetic resonance imaging was used to image pain-associated activity
      in three levels of the neuraxis: the medullary dorsal horn, thalamus, and primary
      somatosensory cortex. In nine subjects, noxious thermal stimuli (46 degrees C)
      were applied to the facial skin at sites within the three divisions of the
      trigeminal nerve (V1, V2, and V3) and also to the ipsilateral thumb. Anatomical
      and functional data were acquired to capture activation across the
      spinothalamocortical pathway in each individual. Significant activation was
      observed in the ipsilateral spinal trigeminal nucleus within the medulla and
      lower pons in response to at least one of the three facial stimuli in all
      applicable data sets. Activation from the three facial stimulation sites
      exhibited a somatotopic organization along the longitudinal (rostrocaudal) axis
      of the brain stem that was consistent with the classically described "onion skin"
      pattern of sensory deficits observed in patients after trigeminal tractotomy. In
      the thalamus, activation was observed in the contralateral side involving the
      ventroposteromedial and dorsomedial nuclei after stimulation of the face and in
      the ventroposterolateral and dorsomedial nuclei after stimulation of the thumb.
      Activation in the primary somatosensory cortex displayed a laminar sequence that
      resembled the trigeminal nucleus, with V2 more rostral, V1 caudal, and V3 medial,
      abutting the region of cortical activation observed for the thumb. These results
      represent the first simultaneous imaging of pain-associated activation at three
      levels of the neuraxis in individual subjects. This approach will be useful for
      exploring central correlates of plasticity in models of experimental and clinical
      pain.

PMID- 12223573
TI  - Paroxysmal dyskinesias in the lethargic mouse mutant.
AB  - Lethargic mutant mice carry a mutation in the CCHB4 gene, which encodes the beta4
      subunit of voltage-regulated calcium channels. These mutants have been shown to
      display a complex neurobehavioral phenotype that includes EEG discharges
      suggestive of absence epilepsy, chronic ataxia, and hypoactivity. The current
      studies demonstrate a fourth element of their phenotype, consisting of transient
      attacks of severe dyskinetic motor behavior. These attacks can be triggered by
      specific environmental and chemical influences, particularly those that stimulate
      locomotor activity. Behavioral and EEG analyses indicate that the attacks do not
      reflect motor epilepsy, but instead resemble a paroxysmal dyskinesia. The
      lethargic mutants provide additional evidence that calcium channelopathies can
      produce paroxysmal dyskinesias and provide a novel model for studying this
      unusual movement disorder.

PMID- 12223574
TI  - Comparing smooth arm movements with the two-thirds power law and the related
      segmented-control hypothesis.
AB  - The movements of the human arm have been extensively studied for a variety of
      goal-directed experimental tasks. Analyses of the trajectory and velocity of the
      arm have led to many hypotheses for the planning strategies that the CNS might
      use. One family of control hypotheses, including minimum jerk, snap and their
      generalizations to higher orders, comprises those that favor smooth movements
      through the optimization of an integral cost function. The predictions of each
      order of this family are examined for two standard experimental tasks: point-to
      point movements and the periodic tracing of figural forms, and compared both with
      experiment and the two-thirds power law. The aim of the analyses is to generalize
      previous numerical observations as well as to examine movement segmentation. It
      is first shown that contrary to recent statements in the literature, the only
      members of this family of control theories that match reaching movement
      experiments well are minimum jerk and snap. Then, for the case of periodic
      drawing, both the ellipse and cloverleaf are examined and the experimentally
      observed power law is derived from a first-principles approach. The results for
      the ellipse are particularly general, representing a unification of the two
      thirds power law and smoothness hypotheses for ellipses of all reasonable
      eccentricities. For complex shapes it is shown that velocity profiles derived
      from the cost-function approach exhibit the same experimental features that were
      interpreted as segmented control by the CNS. Because the cost function contains
      no explicit segmented control, this result casts doubt on such an interpretation
      of the experimental data.

PMID- 12223575
TI  - Limbic thalamic lesions, appetitively motivated discrimination learning, and
      training-induced neuronal activity in rabbits.
AB  - A substantial literature implicates the anterior and mediodorsal (limbic)
      thalamic nuclei and the reciprocally interconnected areas of cingulate cortex in
      learning, memory, and attentional processes. Previous studies have shown that
      limbic thalamic lesions severely impair discriminative avoidance learning and
      that they block development of training-induced neuronal activity in the
      cingulate cortex. The present study investigated the possibility that the limbic
      thalamus and cingulate cortex are involved in reward-based discriminative
      approach learning, wherein head-extension responses yielding oral contact with a
      drinking spout that was inserted into the conditioning chamber after a positive
      conditional stimulus (CS+) were reinforced with a water reward but responses to
      the spout after a negative conditional stimulus (CS-) were not reinforced. In
      this task, the rabbits learned primarily to omit their prepotent responses to the
      spout on CS- trials. Acquisition was severely impaired in rabbits given limbic
      thalamic lesions before training. As during avoidance learning, posterior
      cingulate cortical neurons of control rabbits developed learning-related neuronal
      responses to task-relevant stimuli, but this activity was severely attenuated in
      rabbits with lesions. These results support a general involvement of the
      cingulothalamic circuitry in instrumental approach and avoidance learning. The
      fact that learning consisted of response omission indicated that the
      cingulothalamic role is not limited to acquisition or production of active
      behavioral responses, such as locomotion. It is proposed that cingulothalamic
      neurons mediate associative attention, wherein enhanced neuronal responses to
      stimuli associated with reinforcement facilitate the selection and production of
      task-relevant responses.

PMID- 12223577
TI  - Vanilloid-sensitive afferents activate neurons with prominent A-type potassium
      currents in nucleus tractus solitarius.
AB  - Cranial visceral afferents innervate second-order nucleus tractus solitarius
      (NTS) neurons via myelinated (A-type) and unmyelinated (C-type) axons in the
      solitary tract (ST). A- and C-type afferents often evoke reflexes with distinct
      performance differences, especially with regard to their frequency-dependent
      properties. In horizontal brainstem slices, we used the vanilloid receptor 1
      agonist capsaicin (CAP; 100 nm) to identify CAP-sensitive and CAP-resistant ST
      afferent pathways to second-order NTS neurons and tested whether these two groups
      of neurons had similar intrinsic potassium currents. ST stimulation evoked
      monosynaptic EPSCs identified by minimal synaptic jitter (<150 microsec) and
      divided into two groups: CAP-sensitive (n = 37) and CAP-resistant (n = 22). EPSCs
      in CAP-sensitive neurons had longer latencies (5.1 +/- 0.3 vs 3.6 +/- 0.3 msec; p
      = 0.001) but similar jitter (p = 0.57) compared with CAP-resistant neurons,
      respectively. Transient outward currents (TOCs) were significantly greater in CAP
      sensitive than in CAP-resistant neurons. Steady-state currents were similar in
      both groups. 4-Aminopyridine or depolarized conditioning blocked the TOC, but
      tetraethylammonium had no effect. Voltage-dependent activation and inactivation
      of TOC were consistent with an A-type K+ current, I(KA). In current clamp, the
      activation of I(KA) reduced neuronal excitability and action potential responses
      to ST transmission. Our results suggest that the potassium-channel differences of
      second-order NTS neurons contribute to the differential processing of A- and C
      type cranial visceral afferents beginning as early as this first central neuron.
      I(KA) can act as a frequency transmission filter and may represent a key target
      for the modulation of temporal processing of reflex responsiveness such as within
      the baroreflex arc.

PMID- 12223576
TI  - Vanilloid receptors presynaptically modulate cranial visceral afferent synaptic
      transmission in nucleus tractus solitarius.
AB  - Although the central terminals of cranial visceral afferents express vanilloid
      receptor 1 (VR1), little is known about their functional properties at this first
      synapse within the nucleus tractus solitarius (NTS). Here, we examined whether
      VR1 modulates afferent synaptic transmission. In horizontal brainstem slices,
      solitary tract (ST) activation evoked EPSCs. Monosynaptic EPSCs had low synaptic
      jitter (SD of latency to successive shocks) averaging 84.03 +/- 3.74 microsec (n
      = 72) and were completely blocked by the non-NMDA antagonist 2,3-dihydroxy-6
      nitro-7-sulfonyl-benzo[f]quinoxaline (NBQX). Sustained exposure to the VR1
      agonist capsaicin (CAP; 100 nm) blocked ST EPSCs (CAP-sensitive) in some neurons
      but not others (CAP-resistant). CAP-sensitive EPSCs had longer latencies than CAP
      resistant EPSCs (4.65 +/- 0.27 msec, n = 48 vs 3.53 +/- 0.28 msec, n = 24,
      respectively; p = 0.011), but they had similar jitter. CAP evoked two transient
      responses in CAP-sensitive neurons: a rapidly developing inward current (I(cap))
      (108.1 +/- 22.9 pA; n = 21) and an increase in spontaneous synaptic activity.
      After 3-5 min in CAP, I(cap) subsided and ST EPSCs disappeared. NBQX completely
      blocked I(cap). The VR1 antagonist capsazepine (10-20 microm) attenuated CAP
      responses. Anatomically, second-order NTS neurons were identified by 4-(4
      dihexadecylamino)styryl)-N-methylpyridinium iodide transported from the cervical
      aortic depressor nerve (ADN) to stain central terminals. Neurons with fluorescent
      ADN contacts had CAP-sensitive EPSCs (n = 5) with latencies and jitter similar to
      those of unlabeled monosynaptic neurons. Thus, consistent with presynaptic VR1
      localization, CAP selectively activates a subset of ST axons to release glutamate
      that acts on non-NMDA receptors. Because the CAP sensitivity of cranial afferents
      is exclusively associated with unmyelinated axons, VR1 identifies C-fiber
      afferent pathways within the brainstem.

PMID- 12223578
TI  - Serotonergic modulation of supragranular neurons in rat sensorimotor cortex.
AB  - Numerous observations suggest diverse and modulatory roles for serotonin (5-HT)
      in cortex. Because of the diversity of cell types and multiple receptor subtypes
      and actions of 5-HT, it has proven difficult to determine the overall role of 5
      HT in cortical function. To provide a broader perspective of cellular actions, we
      studied the effects of 5-HT on morphologically and physiologically identified
      pyramidal and nonpyramidal neurons from layers I-III of primary somatosensory and
      motor cortex. We found cell type-specific differences in response to 5-HT. Four
      cell types were observed in layer I: Cajal Retzius, pia surface, vertical axon,
      and horizontal axon cells. The physiology of these cells ranged from fast spiking
      (FS) to regular spiking (RS). In layers II-III, we observed interneurons with FS,
      RS, and late spiking physiology. Morphologically, these cells varied from bipolar
      to multipolar and included basket-like and chandelier cells. 5-HT depolarized or
      hyperpolarized pyramidal neurons and reduced the slow afterhyperpolarization and
      spike frequency. Consistent with a role in facilitating tonic inhibition, 5-HT2
      receptor activation increased the frequency of spontaneous IPSCs in pyramidal
      neurons. In layers II-III, 70% of interneurons were depolarized by 5-HT. In layer
      I, 57% of cells with axonal projections to layers II-III (vertical axon) were
      depolarized by 5-HT, whereas 63% of cells whose axons remain in layer I
      (horizontal axon) were hyperpolarized by 5-HT. We propose a functional
      segregation of 5-HT effects on cortical information processing, based on the
      pattern of axonal arborization.

PMID- 12223579
TI  - Selective reward deficit in mice lacking beta-endorphin and enkephalin.
AB  - It has been impossible to unequivocally identify which endogenous opioids
      modulate the incentive value of rewarding stimuli because these peptides are not
      highly selective for any single opioid receptor subtype. Here, we present
      evidence based on the measurement of instrumental behavior of beta-endorphin and
      enkephalin knock-out mice that both opioid peptides play a positive role. A
      progressive ratio schedule was used to measure how hard an animal would work for
      food reinforcers. The loss of either opioid reduced responding under this
      schedule, regardless of the palatability of the three different formulas of
      reinforcers used. The phenotype of mice lacking both endogenous opioids was
      nearly identical to the phenotype of mice mutant for either individual opioid.
      Responses were tested in nondeprived and deprived feeding states but were reduced
      in beta-endorphin- and enkephalin-deficient mice only when they were maintained
      under nondeprived conditions. Other operant manipulations ruled out variables
      that might contribute nonspecifically to this result such as differences in
      acquisition, early satiation, motor performance deficit, and reduced resistance
      to extinction. In contrast to the effects on instrumental performance, the loss
      of either or both endogenous opioids did not influence preference for water
      flavored with sucrose or saccharin in a two-bottle free-choice drinking paradigm.
      We conclude that both beta-endorphin and enkephalin positively contribute to the
      incentive-motivation to acquire food reinforcers. Because the attenuation of
      operant responding was observed only during a nondeprived motivational state, the
      hedonics of feeding are likely altered rather than energy homeostasis.

PMID- 12223580
TI  - Motoneurons have different membrane resistance during fictive scratching and
      weight support.
AB  - The passive membrane properties of motoneurons may be affected in a behavior
      specific manner because of differences in synaptic drive during different motor
      behaviors. To explore this possibility, the changes in input resistance (R(in))
      and membrane time constant (tau(m)) of single extensor motoneurons were compared
      during two different types of motor activities: fictive scratching and fictive
      weight support. These two activities were selected because the membrane potential
      of extensor motoneurons follows a very different trajectory during fictive
      scratching (multiphasic, mostly rhythmic trajectory) and fictive weight support
      (monophasic, tonic trajectory). The intracellular recordings were performed in
      vivo in the immobilized, decerebrate cat using QX-314-containing microelectrodes
      to block action potentials. The R(in) and tau(m) at rest (control) were reduced
      substantially during all phases of fictive scratching. In contrast, R(in) and
      tau(m) changed only little during fictive weight support. Such a differential
      effect on the membrane resistance was observed even in motoneurons in which the
      peak voltage of the rhythmic depolarization during scratching was similar to the
      peak voltage of the tonic depolarization during weight support. The differential
      effect was attributed mainly to a difference in synaptic drive and, in
      particular, to a larger amount of inhibitory synaptic activity during fictive
      scratching. The present study demonstrates how the same motoneuron can have a
      different membrane resistance while participating in two different behaviors.
      Such tuning of the membrane resistance may provide motoneurons with behavior
      specific integrative capabilities that, in turn, could be used advantageously to
      increase motor performance.

PMID- 12223582
TI  - Selective modification of short-term hippocampal synaptic plasticity and impaired
      memory extinction in mice with a congenitally reduced hippocampal commissure.
AB  - The hippocampus is critical for forming new long-term memories, but the
      contributions of the hippocampal commissure (HC) to memory function and
      hippocampal synaptic plasticity are unclear. To shed light on this issue, we
      characterized behavioral memory and hippocampal synaptic plasticity in two inbred
      mouse strains. BALB/cWah1 mice display a range of corpus callosal defects and an
      intact HC, whereas 9XCA/Wah mice exhibit a complete absence of corpus callosum
      and a greatly reduced HC. No differences between strains were found in long-term
      potentiation (LTP) within two synaptic pathways in hippocampal slices. However,
      paired-pulse facilitation was deficient in area CA1 of slices from 9XCA/Wah, and
      it was rescued by decreasing extracellular [Ca2+], suggesting that presynaptic
      calcium dynamics may be altered in this strain. In addition, contextual fear
      extinction was impaired in 9XCA/Wah mice, but performance on cued fear extinction
      and on 24 hr memory tests for cued and contextual fear conditioning were not
      significantly different between strains. Thus, an intact HC is critical for
      normal extinction of contextual fear. Intact interhemispheric connectivity is not
      required for acquisition or expression of cued and contextual fear conditioning.
      LTP was normal in slices from mice that lacked an intact HC, and this was
      correlated with normal performance on fear conditioning tests. In contrast,
      impaired short-term synaptic plasticity was correlated with defective contextual
      memory extinction in mice lacking an intact HC. Thus, the HC in mice is vital for
      particular aspects of memory function and for short-term synaptic modification in
      specific hippocampal circuits.

PMID- 12223581
TI  - Early motor dysfunction and striosomal distribution of huntingtin microaggregates
      in Huntington's disease knock-in mice.
AB  - Huntington's disease (HD) is characterized by a progressive loss of neurons in
      the striatum and cerebral cortex and is caused by a CAG repeat expansion in the
      gene encoding huntingtin. Mice with the mutation inserted into their own
      huntingtin gene (knock-in mice) are, genetically, the best models of the human
      disease. Here we show for the first time that knock-in mice with 94 CAG repeats
      develop a robust and early motor phenotype at 2 months of age, characterized by
      increased rearing at night. This initial increase in repetitive movements was
      followed by decreased locomotion at 4 and 6 months, despite a normal life span.
      The decrease in striatal enkephalin mRNA that is known to occur at 4 months was
      not present at 2 months, when increased rearing was observed. Both the
      hyperactive and hypoactive phases of motor dysfunction preceded the detection of
      nuclear microaggregates of mutated huntingtin in striatal neurons. Nuclear
      microaggregates, defined as small huntingtin-positive punctas detected by light
      microscopy, were very rare at 4 months but became widely distributed in striatal
      neurons at 6 months. Nuclear inclusions did not appear until 18 months. When
      present, nuclear microaggregates predominated in the striosomal compartment of
      the striatum, providing a possible explanation for the different neuronal
      vulnerability of striatal compartments observed in humans. The early motor
      phenotype observed in the knock-in mouse is reminiscent of repetitive movements
      often observed in early HD and provides a novel opportunity to assess the ability
      of therapies to prevent the initial effects of the mutation in vivo.

PMID- 12223583
TI  - The long-term resetting of a brainstem pacemaker nucleus by synaptic input: a
      model for sensorimotor adaptation.
AB  - The cellular mechanisms behind sensorimotor adaptations, such as the adaptation
      to a sustained change in visual inputs by prism goggles in humans, are not known.
      Here we present a novel example of long-term sensorimotor adaptation in a well
      known neuroethological model, the jamming-avoidance response of a weakly electric
      fish. The adaptation is relatively long lasting, up to 9 hr in vivo, and is
      likely to be mediated by NMDA receptors. We demonstrate in a brain slice
      preparation that the pacemaker nucleus is the locus of adaptation and that it
      responds to long-lasting synaptic stimulation with an increase in the
      postsynaptic spike frequency persisting for hours after stimulus termination. The
      mechanism for the neuronal memory behaves as an integrator, and memory duration
      and strength are quantitatively related to the estimated amount of synaptic
      stimulation. This finding is contrary to the idea that neurons respond solely to
      long-lasting synaptic input by turning down their intrinsic excitability. We show
      that this positive feedback at the cellular level actually contributes to a
      negative feedback loop at the organismic level if the entire neural circuit and
      the behavioral link are considered.

PMID- 12223584
TI  - Movement smoothness changes during stroke recovery.
AB  - Smoothness is characteristic of coordinated human movements, and stroke patients'
      movements seem to grow more smooth with recovery. We used a robotic therapy
      device to analyze five different measures of movement smoothness in the
      hemiparetic arm of 31 patients recovering from stroke. Four of the five metrics
      showed general increases in smoothness for the entire patient population.
      However, according to the fifth metric, the movements of patients with recent
      stroke grew less smooth over the course of therapy. This pattern was reproduced
      in a computer simulation of recovery based on submovement blending, suggesting
      that progressive blending of submovements underlies stroke recovery.

PMID- 12223585
TI  - Reactivation and reconsolidation of long-term memory in the crab Chasmagnathus:
      protein synthesis requirement and mediation by NMDA-type glutamatergic receptors.
AB  - Experiments with invertebrates support the view that intracellular events
      subserving the consolidation phase of memory are preserved across evolution.
      Here, we investigate whether such evolutionary persistence extends to
      reconsolidation mechanisms, which have recently received special attention in
      vertebrate studies. For this purpose, the memory model of the crab Chasmagnathus
      is used. A visual danger stimulus (VDS) elicits crab escaping, which declines
      after a few stimulus presentations. The long-lasting retention of this decrement,
      called context-signal memory (CSM), is mediated by an association between
      contextual cues of the training site and the VDS. The present results show
      amnesia for CSM in crabs re-exposed at 24 hr (day 2) for 5 min to the learning
      context, 24 hr after training, and injected with one of two amnesic agents, then
      tested 24 hr later. Agents and timing were either 15 microg of cycloheximide
      given between 1 hr before and 4 hr after re-exposure or 1 microg/gm (+)-5-methyl
      10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine given between 1 hr before and
      2 hr after re-exposure. The amnesic effects are specific to behavior that occurs
      a long time after reactivation but not a short time after. No CSM deficit is
      produced by such agents when crabs are exposed to a context different from that
      of training. Findings are consistent with those reported for vertebrates, with
      both showing that reactivation induces a recapitulation of the postacquisition
      cascade of intracellular events. The agreement between results from such
      phylogenetically disparate animals suggests that evolution may have adopted a
      given molecular cascade as the preferred means of encoding experiences in the
      nervous system.

PMID- 12223586
TI  - Chronic morphine induces downregulation of spinal glutamate transporters:
      implications in morphine tolerance and abnormal pain sensitivity.
AB  - Tolerance to the analgesic effects of an opioid occurs after its chronic
      administration, a pharmacological phenomenon that has been associated with the
      development of abnormal pain sensitivity such as hyperalgesia. In the present
      study, we examined the role of spinal glutamate transporters (GTs) in the
      development of both morphine tolerance and associated thermal hyperalgesia.
      Chronic morphine administered through either intrathecal boluses or continuous
      infusion induced a dose-dependent downregulation of GTs (EAAC1 and GLAST) in the
      rat's superficial spinal cord dorsal horn. This GT downregulation was mediated
      through opioid receptors because naloxone blocked such GT changes. Morphine
      induced GT downregulation reduced the ability to maintain in vivo glutamate
      homeostasis at the spinal level, because the hyperalgesic response to exogenous
      glutamate was enhanced, including an increased magnitude and a prolonged time
      course, in morphine-treated rats with reduced spinal GTs. Moreover, the
      downregulation of spinal GTs exhibited a temporal correlation with the
      development of morphine tolerance and thermal hyperalgesia. Consistently, the GT
      inhibitor l-trans-pyrrolidine-2-4-dicarboxylate (PDC) potentiated, whereas the
      positive GT regulator riluzole reduced, the development of both morphine
      tolerance and thermal hyperalgesia. The effects from regulating spinal GT
      activity by PDC were at least in part mediated through activation of the NMDA
      receptor (NMDAR), because the noncompetitive NMDAR antagonist MK-801 blocked both
      morphine tolerance and thermal hyperalgesia that were potentiated by PDC. These
      results indicate that spinal GTs may contribute to the neural mechanisms of
      morphine tolerance and associated abnormal pain sensitivity by means of
      regulating regional glutamate homeostasis.

PMID- 12223587
TI  - Gustatory processing in thoracic local circuits of locusts.
AB  - Recent reviews highlight a longstanding controversy about how different taste
      qualities are coded in the CNS. To address this issue, we have analyzed gustatory
      coding in the relatively simple and accessible nervous system of the locust, in
      which neural responses and gustatory elicited behavior are readily comparable.
      The intracellular responses of a population of spiking local interneurons in the
      metathoracic ganglion that receive monosynaptic inputs from chemosensory
      afferents were analyzed in response to stimulation with droplets of four
      behaviorally relevant chemicals: sodium chloride, sucrose, lysine glutamate, and
      nicotine hydrogen tartrate. There was a significant positive correlation between
      chemical concentration and response duration and the number of spikes evoked in
      81% of interneurons sampled. The threshold of sensitivity to different chemicals
      varied but was consistent between all interneurons tested, being most sensitive
      to nicotine hydrogen tartrate and least sensitive to sucrose. Each interneuron
      responded similarly to specific chemicals at single concentrations. Interneurons
      that responded phasically to one chemical responded similarly to others, whereas
      interneurons that responded phasotonically to one stimulus also did so to others.
      Hindleg motor neurons also responded in a concentration-dependent manner to all
      test chemicals. Therefore, we found no interneurons or motor neurons that
      responded only to specific chemicals. We discuss the responses of the local
      circuit neurons in relation to the known chemically evoked behavioral responses
      of locusts and suggest that the aversiveness of a chemical, rather than its
      identity, is encoded directly in the local circuits.

PMID- 12223588
TI  - Signals in macaque striate cortical neurons that support the perception of glass
      patterns.
AB  - Glass patterns are texture stimuli made by pairing randomly placed dots with
      partners at specific offsets. The strong percept of global form that arises from
      the sparse local orientation cues has made these patterns the subject of
      psychophysical investigations, yet neuronal responses to Glass patterns have not
      been studied. We measured the responses of neurons in macaque striate cortex (V1)
      to dynamic, translational Glass patterns as a function of dot separation and dot
      pair orientation. Responses were selective, but were on average more than an
      order of magnitude weaker than responses to sinusoidal gratings. Response and
      selectivity were greatest when the dot-pair orientation matched that of the
      preferred grating and when dot separation was between one-quarter and one-half of
      the spatial period of the optimal grating; changing the dot-pair separation or
      inverting the contrast of one of the dots radically changed the orientation
      selectivity. We computed the expected responses for a receptive field model to
      translational Glass patterns and found that the complexity of our V1 tuning
      curves could be understood in terms of the responses of linear filters to pairs
      of dots. This modeling connects our understanding of V1 receptive fields as
      rectified, quasi-linear filters with results from psychophysical studies of Glass
      patterns. Our results provide a basis for studying how subsequent visual areas
      integrate weak, local signals into global form percepts.

PMID- 12223589
TI  - A Single-Seed Assay for Endo-[beta]-Mannanase Activity from Tomato Endosperm and
      Radicle Tissues.
AB  - Completion of germination (radicle emergence) is an all-or-none developmental
      event for an individual seed. Variation in germination timing among seeds in a
      population therefore reflects variation among seeds in the rates or extents of
      physiological or biochemical processes prior to radicle emergence. For tomato
      (Lycopersicon esculentum Mill.) seeds, correlative evidence suggests that endo
      [beta]-mannanase activity weakens the endosperm cap tissue opposite the radicle
      tip to permit radicle emergence. To test whether endo-[beta]-mannanase activity
      is causally related to germination rates, we have developed a sensitive assay
      suitable for use with individual radicle tips or endosperm caps. We show that
      endo-[beta]-mannanase activity varies at least 100-fold and often more than 1000
      fold among individual inbred tomato seeds prior to radicle emergence. Other
      sources of variation (tissue size and experimental error) were evaluated and
      cannot account for this range of activity. Endo-[beta]-mannanase activity was
      generally 10-fold greater in leachates from endosperm caps than from radicle
      tips. Release of reducing sugars from individual endosperm caps also varied over
      a considerable (9-fold) range. These extreme biochemical differences among
      individual tomato seeds prior to radicle emergence indicate that results obtained
      from bulk samples could be misleading if it is assumed that all seeds exhibit the
      "average" behavior.

PMID- 12223590
TI  - Endo-[beta]-Mannanase Activity from Individual Tomato Endosperm Caps and Radicle
      Tips in Relation to Germination Rates.
AB  - Endo-[beta]-mannanase is hypothesized to be a rate-limiting enzyme in endosperm
      weakening, which is a prerequisite for radicle emergence from tomato
      (Lycopersicon esculentum Mill.) seeds. Using a sensitive, single-seed assay, we
      have measured mannanase activity diffusing from excised tomato endosperm caps
      following treatments that alter the rate or percentage of radicle emergence. Most
      striking was the 100- to more than 10,000-fold range of mannanase activity
      detected among individual seeds of highly inbred tomato lines, which would not be
      detected in pooled samples. In some cases a threshold-type relationship between
      mannanase activity and radicle emergence was observed. However, when radicle
      emergence was delayed or prevented by osmoticum or abscisic acid, the initial
      increase in mannanase activity was unaffected or even enhanced. Partially dormant
      seed lots displayed a bimodal distribution of activity, with low activity
      apparently associated with dormant seeds in the population. Gibberellin- and
      abscisic acid-deficient mutant seeds exhibited a wide range of mannanase
      activity, consistent with their variation in hormonal sensitivity. Although the
      presence of mannanase activity in the endosperm cap is consistently associated
      with radicle emergence, it is not the sole or limiting factor under all
      conditions.

PMID- 12223591
TI  - Blockage of Brassinosteroid Biosynthesis and Sensitivity Causes Dwarfism in
      Garden Pea.
AB  - Endogenous brassinosteroids (BRs) in the dwarf mutants lka and lkb of garden pea
      (Pisum sativum L.) and comparable wild-type plants were quantified by gas
      chromatography-selected ion monitoring using deuterated internal standards. In
      young shoots of the lkb mutant, the levels of brassinolide, castasterone, and 6
      deoxocastasterone were 23-, 22-, and 9-fold lower, respectively, than those of
      wild-type plants. Applications of brassinolide, castasterone, typhasterol, 3
      dehydroteasterone, and teasterone normalized internode growth of lkb seedlings.
      These findings indicate that the lkb plants are BR-deficient mutants, probably as
      a consequence of a block in the BR biosynthetic pathway prior to the production
      of teasterone. Young shoots of lka plants contained only 50% less brassinolide
      and 5 times more castasterone than the equivalent wild-type tissues. The lka
      seedlings were approximately 100 times less responsive to brassinolide than the
      lkb mutant, and application of castasterone had only a marginal effect on lka
      internode growth, suggesting that the lka lesion results in impaired sensitivity
      to BR.

PMID- 12223592
TI  - Ultraviolet B-Sensitive Rice Cultivar Deficient in Cyclobutyl Pyrimidine Dimer
      Repair.
AB  - Repair of cyclobutyl pyrimidine dimers (CPDs) in DNA is essential in most
      organisms to prevent biological damage by ultraviolet (UV) light. In higher
      plants tested thus far, UV-sensitive strains had higher initial damage levels or
      deficient repair of nondimer DNA lesions but normal CPD repair. This suggested
      that CPDs might not be important for biological lesions. The photosynthetic
      apparatus has also been proposed as a critical target. We have analyzed CPD
      induction and repair in the UV-sensitive rice (Oryza sativa L.) cultivar Norin 1
      and its close relative UV-resistant Sasanishiki using alkaline agarose gel
      electrophoresis. Norin 1 is deficient in cyclobutyl pyrimidine dimer
      photoreactivation and excision; thus, UV sensitivity correlates with deficient
      dimer repair.

PMID- 12223593
TI  - Effect of Xyloglucan Oligosaccharides on Growth, Viscoelastic Properties, and
      Long-Term Extension of Pea Shoots.
AB  - The growth-promoting effect of xyloglucan-derived oligosaccharides was
      investigated using a bioassay with entire pea (Pisum sativum L., var Alaska)
      shoots. After a 24-h incubation period at 25[deg]C, xyloglucan oligosaccharide
      (XGO) solutions with concentrations of 10-6 M notably increased the growth rate
      of pea shoots, whereas the same oligosaccharides at 10-7 M were less effective.
      To investigate the possible correlation between growth rate changes in the XGO
      treated shoots and changes in the wall mechanical properties of their growing
      regions (third internodes), we used a short-term creep assay. The promotion of
      elongation by XGOs was reflected in an enhancement of the viscoelasticity of the
      growing regions of the shoots. To show whether this effect on wall viscoelastic
      properties was the cause or a consequence of their growth promotion, we tested
      the effect of XGOs on the long-term extension of isolated cell walls. We
      characterized an acid-induced extension in isolated cell walls from pea shoots
      that was not inhibited by preincubation in neutral buffers. Exogenously added
      XGOs did not alter the pattern of pea segment extension at any pH tested,
      indicating that XGOs have no direct effect on cell wall viscoelasticity. Finally,
      preincubation of pea segments in neutral buffers with XGOs enhanced their
      capacity to extend under acidic conditions. This finding suggests that XGOs at a
      neutral pH can act via transglycosylation, weakening the wall matrix and making
      the wall more responsive to other mechanisms of acid-induced extension as an
      expansin-mediated extension.

PMID- 12223594
TI  - Oscillations in H+ and Ca2+ Ion Fluxes around the Elongation Region of Corn Roots
      and Effects of External pH.
AB  - Net fluxes of H+ and Ca2+ around the elongation region of low-salt corn (Zea mays
      L.) roots were measured using the microelectrode ion flux estimation (MIFE)
      technique. At pH 5.2 two oscillatory components were found. Fast, 7-min
      oscillations in H+ flux were superimposed on slow oscillations of about 1.5 h.
      Fast oscillations in Ca2+ flux showed a strong dependence on the H+ oscillations
      and were normally leading in phase by about 1 to 1.5 min. Both oscillatory
      components were strongly affected by external pH values. Preincubation for 20 h
      in buffered pH 4.0 solution suppressed the slow oscillatory component and caused
      huge H+ influxes in the elongation region. The fast oscillations were 8 times
      larger in amplitude and were slightly lengthened. Preincubation at pH 6.0 did not
      suppress the rhythmic character of the ion fluxes but it shifted the average H+
      flux to greater efflux. The fast and slow oscillatory components of H+ flux seem
      to relate to biophysical and biochemical mechanisms of intracellular pH
      homeostasis, respectively. The origin of the Ca2+ flux oscillations is discussed
      in terms of the "weak acid Donnan Manning" model of cell wall ion exchanges.

PMID- 12223595
TI  - Reexamination of the Intracellular Localization of de Novo Purine Synthesis in
      Cowpea Nodules.
AB  - Sucrose and Percoll density gradient centrifugation were used to separate
      organelles from the central zone tissue of cowpea (Vigna unguiculata L. Walp. cv
      Vita 3: Bradyrhizobium strain CB 756) nodules. Enzyme activity analysis has shown
      that both plastids and mitochondria have a full complement of enzymes for de novo
      purine synthesis. In vitro activities of individual component enzymes
      (glycinamide ribonucleotide synthetase, EC 6.3.4.13; glycinamide ribonucleotide
      transformylase, EC 2.1.2.2; aminoimidazole ribonucleotide synthetase, EC 6.3.3.1;
      aminoimidazole carboxamide ribonucleotide transformylase, EC 6.3.2.6; and
      adenylosuccinate-AMP lyase, EC 4.3.2.2) as well as of the whole purine pathway
      (from ribose-5-phosphate to inosine monophosphate) were similar in the two
      organelles. No significant cytosolic or bacteroidal activity of any of the purine
      pathway enzymes was detected on assay. These findings are contrary to earlier
      studies (M.J. Boland, K.R. Schubert [1983] Arch Biochem Biophys 220: 179-187;
      B.J. Shelp C.A. Atkins, P.J. Storer, D.T. Canvin [1983] Arch Biochem Biophys 224:
      429-441) that concluded that enhanced expression of purine synthesis in nodules
      of ureide-forming species is localized to plastids. Significantly increased
      recovery of activity of key pathway enzymes (particularly of labile
      aminoimidazole ribonucleotide synthetase) coupled with improved assay methods and
      the use of Percoll in addition to sucrose for gradient centrifugation have
      together contributed to much higher reaction rates and more definitive analyses
      of particulate fractions.

PMID- 12223597
TI  - Hormonal Regulation of Dormancy in Developing Sorghum Seeds.
AB  - The role of abscisic acid (ABA) and gibberellic acid (GA) in determining the
      dormancy level of developing sorghum (Sorghum bicolor [L.] Moench.) seeds from
      varieties presenting contrasting preharvest sprouting behavior (Redland B2,
      susceptible; IS 9530, resistant) was investigated. Panicles from both varieties
      were sprayed soon after pollination with fluridone or paclobutrazol to inhibit
      ABA and GA synthesis, respectively. Fluridone application to the panicles
      increased germinability of Redland B2 immature caryopses, whereas early treatment
      with paclobutrazol completely inhibited germination of this variety during most
      of the developmental period. Incubating caryopses in the presence of 100 [mu]M
      GA4+7 overcame the inhibitory effect of paclobutrazol, but also stimulated
      germination of seeds from other treatments. IS 9530 caryopses presented
      germination indices close to zero until physiological maturity (44 d after
      pollination) in control and paclobutrazol-treated particles. However, fluridone
      treated caryopses were released from dormancy earlier than control and
      paclobutrazol-treated caryopses. Incubation in the presence of GA4+7 stimulated
      germination of caryopses from all treatments. Our results support the proposition
      that a low dormancy level (which is related to a high preharvest sprouting
      susceptibility) is determined not only by a low embryonic sensitivity to ABA, but
      also by a high GA content or sensitivity.

PMID- 12223596
TI  - Conversion of Chlorophyll b to Chlorophyll a and the Assembly of Chlorophyll with
      Apoproteins by Isolated Chloroplasts.
AB  - The photosynthetic apparatus is reorganized during acclimation to various light
      environments. During adaptation of plants grown under a low-light to high-light
      environment, the light-harvesting chlorophyll a/b-protein complexes decompose
      concomitantly with an increase in the core complex of photosystem II. To study
      the mechanisms for reorganization of photosystems, the assembly of chlorophyll
      with apoproteins was investigated using isolated chloroplasts. When
      [14C]chlorophyllide b was incubated with chloroplasts in the presence of phytyl
      pyrophosphate, it was esterified and some of the [14C]chlorophyll b was converted
      to [14C]chlorophyll a via 7-hydroxymethyl chlorophyll. [14C]Chlorophyll a and b
      were incorporated into chlorophyll-protein complexes. Light-harvesting
      chlorophyll a/b-protein complexes of PSII had a lower [14C]chlorophyll a to
      [14C]chlorophyll b ratio than P700-chlorophyll a-protein complexes, indicating
      the specific binding of chlorophyll to apoproteins in our systems. 7
      Hydroxymethyl chlorophyll, an intermediate molecule from chlorophyll b to
      chlorophyll a, did not become assembled with any apoproteins. These results
      indicate that chlorophyll b is released from light-harvesting chlorophyll a/b
      protein complexes of photosystem II and converted to chlorophyll a via 7
      hydroxymethyl chlorophyll in the lipid bilayer and is then used for the formation
      of core complexes of photosystems. These mechanisms provide the fast, fine
      regulation of the photosynthetic apparatus during construction of photosystems.

PMID- 12223598
TI  - Endo-[beta]-Mannanase Activity Present in Cell Wall Extracts of Lettuce Endosperm
      prior to Radicle Emergence.
AB  - Lettuce (Lactuca sativa L.) endosperm cell walls isolated prior to radicle
      emergence underwent autohydrolysis, the rate of which was correlated with whether
      radicle emergence would subsequently occur. Extraction of endosperm cell walls
      with 6 M LiCl suppressed autohydrolysis, and the desalted extract possessed
      activity that was capable of hydrolyzing purified locust bean galactomannan but
      not arabinogalactan, carboxymethylcellulose, glucomannan, polygalacturonic acid,
      tomato galactomannan, or native lettuce endosperm cell walls. Some hydrolytic
      activity was detected on endosperm cell walls if they were modified by partial
      trifluoroacetic acid hydrolysis or pretreatment with guanidinium thiocyanate. In
      extended incubations the cell wall enzyme extract released only large molecular
      mass fragments from locust bean galactomannan, indicating primarily endo
      activity. Galactomannan-hydrolyzing activity in the cell wall extract increased
      as a function of imbibition time and was greatest just prior to radicle
      emergence. Thermoinhibition (imbibition at 32[deg]C) or treatment with abscisic
      acid at a temperature optimal for germination (25[deg]C) suppressed both
      germination and endosperm cell wall mannanase activity, whereas alleviation of
      thermoinhibition with gibberellic acid was accompanied by significant enhancement
      of mannanase activity. We conclude that a cell wall-bound endo-[beta]-mannanase
      is expressed in lettuce endosperm prior to radicle emergence and is regulated by
      the same conditions that govern germination.

PMID- 12223599
TI  - Sterol Modulation of the Plasma Membrane H+-ATPase Activity from Corn Roots
      Reconstituted into Soybean Lipids.
AB  - A partially purified H+-ATPase from the plasma membrane (PM) of corn (Zea mays
      L.) roots was inserted into vesicles prepared with soybean (Glycine max L.)
      phospholipids and various concentrations of individual sterols using either a
      freeze-thaw sonication or an octylglucoside dilution procedure. Both methods
      yielded a functional enzyme that retained its native characteristics. We have
      investigated the effects of typical plant sterols (i.e. sitosterol, stigmasterol,
      and 24-methylcholesterol) on both ATP hydrolysis and H+ pumping by the
      reconstituted corn root PM ATPase. We have also checked the influence of
      cholesterol and of two unusual sterols, 24-methylpollinastanol and 14[alpha],24
      dimethylcholest-8-en-3[beta]-ol. Here we present evidence for a sterol modulation
      of the plant PM H+-ATPase activity. In particular, cholesterol and stigmasterol
      were found to stimulate the pump, especially when present at 5 mol%, whereas all
      of the other sterols tested behaved as inhibitors at any concentration in
      proteoliposomes. In all situations H+ pumping was shown to be more sensitive to a
      sterol environment than was ATP hydrolysis. Our results suggest the occurrence of
      binding sites for sterols on the plant PM H+-ATPase.

PMID- 12223600
TI  - Cooperation and Competition between Adenylate Kinase, Nucleoside Diphosphokinase,
      Electron Transport, and ATP Synthase in Plant Mitochondria Studied by 31P-Nuclear
      Magnetic Resonance.
AB  - Nucleotide metabolism in potato (Solanum tuberosum) mitochondria was studied
      using 31P-nuclear magnetic resonance spectroscopy and the O2 electrode.
      Immediately following the addition of ADP, ATP synthesis exceeded the rate of
      oxidative phosphorylation, fueled by succinate oxidation, due to mitochondrial
      adenylate kinase (AK) activity two to four times the maximum activity of ATP
      synthase. Only when the AK reaction approached equilibrium was oxidative
      phosphorylation the primary mechanism for net ATP synthesis. A pool of
      sequestered ATP in mitochondria enabled AK and ATP synthase to convert AMP to ATP
      in the presence of exogenous inorganic phosphate. During this conversion, AK
      activity can indirectly influence rates of oxidation of both succinate and NADH
      via changes in mitochondrial ATP. Mitochondrial nucleoside diphosphokinase, in
      cooperation with ATP synthase, was found to facilitate phosphorylation of
      nucleoside diphosphates other than ADP at rates similar to the maximum rate of
      oxidative phosphorylation. These results demonstrate that plant mitochondria
      contain all of the machinery necessary to rapidly regenerate nucleoside
      triphosphates from AMP and nucleoside diphosphates made during cellular
      biosynthesis and that AK activity can affect both the amount of ADP available to
      ATP synthase and the level of ATP regulating electron transport.

PMID- 12223601
TI  - The Propagation of Slow Wave Potentials in Pea Epicotyls.
AB  - Slow wave potentials are considered to be electric long-distance signals specific
      for plants, although there are conflicting ideas about a chemical, electrical, or
      hydraulic mode of propagation. These ideas were tested by comparing the
      propagation of hydraulic and electric signals in epicotyls of pea (Pisum sativum
      L). A hydraulic signal in the form of a defined step increase in xylem pressure
      (Px) was applied to the root of intact seedlings and propagated nearly instantly
      through the epicotyl axis while its amplitude decreased with distance from the
      pressure chamber. This decremental propagation was caused by a leaky xylem and
      created an axial Px gradient in the epicotyl. Simultaneously along the epicotyl
      surface, depolarizations appeared with lag times that increased acropetally with
      distance from the pressure chamber from 5 s to 3 min. When measured at a constant
      distance, the lag times increased as the size of the applied pressure steps
      decreased. We conclude that the Px gradient in the epicotyl caused local
      depolarizations with acropetally increasing lag times, which have the appearance
      of an electric signal propagating with a rate of 20 to 30 mm min-1. This static
      description of the slow wave potentials challenges its traditional classification
      as a propagating electric signal.

PMID- 12223602
TI  - Water Deficit Rapidly Stimulates the Activity of a Protein Kinase in the
      Elongation Zone of the Maize Primary Root.
AB  - The mechanisms by which plants detect water deficit and transduce that signal
      into adaptive responses is unknown. In maize (Zea mays L.) seedlings, primary
      roots adapt to low water potentials such that substantial rates of elongation
      continue when shoot growth is completely inhibited. In this study, in-gel protein
      kinase assays were used to determine whether protein kinases in the elongation
      zone of the primary root undergo activation or inactivation in response to water
      deficit. Multiple differences were detected in the phosphoprotein content of root
      tips of water-stressed compared with well-watered seedlings. Protein kinase
      assays identified water-deficit-activated protein kinases, including a 45-kD,
      Ca2+-independent serine/threonine protein kinase. Water-deficit activation of
      this kinase occurred within 30 min after transplanting seedlings to conditions of
      low water potential and was localized to the elongation zone, was independent of
      ABA accumulation, and was unaffected by cycloheximide-mediated inhibition of
      protein translation. These results provide evidence that the 45-kD protein kinase
      acts at an early step in the response of maize primary roots to water deficit and
      is possibly involved in regulating the adaptation of root growth to low water
      potential.

PMID- 12223603
TI  - Heat Denaturation Profiles of Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase
      (Rubisco) and Rubisco Activase and the Inability of Rubisco Activase to Restore
      Activity of Heat-Denatured Rubisco.
AB  - We compared the heat-denaturation profiles of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco) and Rubisco activase and further examined the
      ability of Rubisco activase to restore the activity of heat-denatured Rubisco
      originally reported (E. Sanchez de Jimenez, L. Medrano, and E. Martinez-Barajas
      [1995] Biochemistry 34: 2826-2831). Rubisco was heat-treated in both the
      carbamylated and uncarbamylated forms and in the presence and absence of 10 mM
      dithiothreitol (DTT). Both forms were highly resistant to heat denaturation and
      further protection was gained in the presence of DTT. A 50% loss in total
      activity occurred after 1 h at 57.5 and 55.2[deg]C for uncarbamylated Rubisco and
      at 60.2 and 59.6[deg]C for carbamylated Rubisco, in each case with and without
      DTT, respectively. In contrast, Rubisco activase lost 50% activity after only 5
      min at 33[deg]C and the loss in activity was not affected by the presence of
      Rubisco. When Rubisco, heat-denatured to various extents, was incubated at room
      temperature with Rubisco activase or bovine serum albumin as a control, Rubisco
      activase did not have a significant specific ability to restore Rubisco activity.
      We conclude that Rubisco activase alone does not have the ability to restore the
      activity of heat-denatured Rubisco and is unlikely to protect or restore Rubisco
      activity from heat denaturation in vivo because it is more heat-labile than
      Rubisco.

PMID- 12223604
TI  - Responses of Antioxidants to Paraquat in Pea Leaves (Relationships to
      Resistance).
AB  - Differnential sensitivity to the oxidant paraquat was observed in pea (Pisum
      sativum L.) based on cultivar and leaf age. To assess contributions of inductive
      responses of the antioxidant enzymes in short-term resistance to oxidative
      damage, activities of glutathione reductase (GR), superoxide dismutase (SOD), and
      ascorbate peroxidase (APX) and transcript levels for plastidic GR, Cu,Zn SOD, and
      cytosolic APX were determined. Responses to paraquat exposure from three
      different leaf age classes of pea were studied. Resistance was correlated with
      leaf age, photosynthetic rates, enzyme activities, and pretreatment levels of
      plastid GR and plastid Cu,Zn SOD transcripts. In response to paraquat, small
      increases in activities of GR and APX were observed in the more resistant leaves.
      These changes were not reflected at the mRNA level for the plastidic GR or Cu,Zn
      SOD. Paraquat-mediated increases in cytosolic APX mRNA occurred in all leaf
      types, irrespective of resistance. Developmentally controlled mechanisms
      determining basal antioxidant enzyme activities, and not inductive responses,
      appear to be critical factors mediating short-term oxidative stress resistance.

PMID- 12223605
TI  - Phloem Glutamine and the Regulation of O2 Diffusion in Legume Nodules.
AB  - The aim of the present study was to test the hypothesis that the N content or the
      composition of the phloem sap that supplies nodulated roots may play a role in
      the feedback regulation of nitrogenase activity by increasing nodule resistance
      to O2 diffusion. Treating shoots of lupin (Lupinus albus cv Manitoba) or soybean
      (Glycine max L. Merr. cv Maple Arrow) with 100 [mu]L L-1 NH3 caused a 1.3-fold
      (lupin) and 2.6-fold (soybean) increase in the total N content of phloem sap
      without altering its C content. The increase in phloem N was due primarily to a
      4.8-fold (lupin) and 10.5-fold (soybean) increase in the concentration of
      glutamine N. In addition, there was a decline in both the apparent nitrogenase
      activity and total nitrogenase activity that began within 4 h and reached about
      54% of its initial activity within 6 h of the start of the NH3 treatment.
      However, the potential nitrogenase activity values in the treated plants were not
      significantly different from those of the control plants. These results provide
      evidence that changes in the N composition of the phloem sap, particularly the
      glutamine content, may increase nodule resistance to O2 diffusion and, thereby,
      down-regulate nodule metabolism and nitrogenase activity by controlling the
      supply of O2 to the bacteria-infected cells.

PMID- 12223606
TI  - Activation of Plant Plasma Membrane Ca2+-Permeable Channels by Race-Specific
      Fungal Elicitors.
AB  - The response of plant cells to invading pathogens is regulated by fluctuations in
      cytosolic Ca2+ levels that are mediated by Ca2+-permeable channels located at the
      plasma membrane of the host cell. The mechanisms by which fungal elicitors can
      induce Ca2+ uptake by the host cell were examined by the application of
      conventional patch-clamp techniques. Whole-cell and single-channel experiments on
      tomato (Lycopersicon esculentum L.) protoplasts revealed a race-specific fungal
      elicitor-induced activation of a plasma membrane Ca2+-permeable channel. The
      presence of the fungal elicitor resulted in a greater probability of channel
      opening. Guanosine 5[prime]-[[beta]-thio]diphosphate, a GDP analog that locks
      heterotrimeric G-proteins into their inactivated state, abolished the channel
      activation induced by the fungal elicitor, whereas guanosine 5[prime][[gamma]
      thio]triphosphate, a nonhydrolyzable GTP analog that locks heterotrimeric G
      proteins into their activated state, produced an effect similar to that observed
      with the fungal elicitor. Mastoparan, which stimulates GTPase activity, mimicked
      the effect of GTP[[gamma]]S. The addition of HA1004 (a protein kinase inhibitor)
      in the presence of the elicitor totally abolished channel activity, whereas
      okadaic acid (a protein phosphatase inhibitor) moderately enhanced channel
      activity, suggesting that the activation of the channel by fungal elicitors is
      modulated by a heterotrimeric G-protein-dependent phosphorylation of the channel
      protein.

PMID- 12223607
TI  - Influence of Gene Dosage on Carbohydrate Synthesis and Enzymatic Activities in
      Endosperm of Starch-Deficient Mutants of Maize.
AB  - In cereals, starch is synthesized in endosperm cells, which have a ploidy level
      of three. By studying the allelic dosage of mutants affecting starch formation in
      maize (Zea mays L.) kernels, we determined the effect of down-regulated enzyme
      activity on starch accumulation and the activity of associated enzymes of
      carbohydrate metabolism. We found a direct relationship between the amount of
      starch produced in the endosperm and the gene dosage of amylose extender-1,
      brittle-2, shrunken1, and sugary-1 mutant alleles. Changes in starch content were
      found to be caused by changes in the duration as well as the rate of starch
      synthesis, depending on the mutant. Branching enzyme, ADP-glucose
      pyrophosphorylase, and sucrose synthase activities were linearly reduced in
      endosperm containing increasing dosages of amylose extender-1, brittle-2, and
      shrunken-1 alleles, respectively. De-branching enzyme activity declined only in
      the presence of two or three copies of sugary-1. No enzyme-dosage relationship
      occurred with the dull1 mutant allele. All mutants except sugary-1 displayed
      large increases (approximately 2- to 5-fold) in activity among various enzymes
      unrelated to the structural gene. This occurred in homozygous recessive
      genotypes, as did elevated concentrations of soluble sugars, and differed in
      magnitude and distribution among enzymes according to the particular mutation.

PMID- 12223608
TI  - Blazing New Trails (Pollen Tube Guidance in Flowering Plants).

PMID- 12223609
TI  - Making Sense of Senescence (Molecular Genetic Regulation and Manipulation of Leaf
      Senescence).

PMID- 12223610
TI  - Cinnamyl Alcohol Dehydrogenase: Identification of New Sites of Promoter Activity
      in Transgenic Poplar.
AB  - Stem sections from poplar that were stably transformed with a eucalypt cinnamyl
      alcohol dehydrogenase promoter-[beta]-glucuronidase construct were prepared by
      using either a technique routinely used in herbaceous species or a technique
      designed to take into account the particular anatomy of woody plants. Although
      both preparation techniques confirmed the pattern of expression previously
      observed (C. Feuillet, V. Lauvergeat, C. Deswarte, G. Pilate, A. Boudet and J.
      Grima-Pettenati [1995] Plant Mol Biol 27: 651-657), the latter technique also
      allowed the detection of other sites of promoter activity not revealed by the
      first technique. In situ hybridization confirmed the expression pattern obtained
      with the second sample preparation technique.

PMID- 12223611
TI  - Observations of Ice Nucleation and Propagation in Plants Using Infrared Video
      Thermography.
AB  - We evaluated the use of infrared (IR) video thermography to observe directly ice
      nucleation and propagation in plants. An imaging radiometer with an HgCdTe long
      wave (8-12 [mu]m) detector was utilized to image the thermal response of plants
      during freezing. IR images were analyzed in real time and recorded on videotape.
      Information on the videotape was subsequently accessed and analyzed utilizing IR
      image analysis software. Freezing of water droplets as small as 0.5 [mu]L was
      clearly detectable with the radiometer. Additionally, a comparison of temperature
      tracking data collected by the radiometer with data collected with thermocouples
      showed close correspondence. Monitoring of an array of plant species under
      different freezing conditions revealed that ice nucleation and propagation are
      readily observable by thermal imaging. In many instances, the ice nucleation
      active bacterium Pseudomonas syringae placed on test plants could be seen to
      initiate freezing of the whole plant. Apparent ice nucleation by intrinsic
      nucleators, despite the presence of ice nucleation-active bacteria, was also
      evident in some species. Floral bud tissues of peach (Prunus persica) could be
      seen to supercool below the temperature of stem tissues, and ice nucleation at
      the site of insertion of the thermocouple was frequently observed. Rates of
      propagation of ice in different tissues were also easily measured by thermal
      imaging. This study demonstrates that IR thermography is an excellent method for
      studying ice nucleation and propagation in plants.

PMID- 12223612
TI  - Purification and Characterization of a [beta]-D-Xylosidase and an Endo-Xylanase
      from Wheat Flour.
AB  - A [beta]-D-xylosidase and an endo-xylanase were purified from European wheat
      (Triticum aestivum) flour. The [beta]-D-xylosidase had a molecular weight of
      approximately 64,000 and an isoelectric point of 5.5. It hydrolyzed p-nitrophenyl
      [beta]-D-xylopyranoside and xylo-oligosaccharides and released D-xylose units
      from wheat arabinoxylan and oat spelts xylan. An endo-xylanase with a molecular
      weight of approximately 55,000 was also obtained and it consisted of a number of
      isoforms with isoelectric points between 4.0 and 5.0. The action of the isolated
      endo-xylanase depended on the degree of substitution of the polysaccharide.
      Unbranched polymers were preferentially hydrolyzed. Since xylo-oligosaccharides
      were not hydrolyzed, the enzyme appeared to need at least five or more
      consecutive unsubstituted xylose units. Finally, an [alpha]-L-arabinofuranosidase
      that hydrolyzed p-nitrophenyl-[alpha]-L-arabinofuranoside was partially purified.

PMID- 12223613
TI  - Polyamines and Pectins (I. Ion Exchange and Selectivity).
AB  - The ion-binding and -exchange properties of putrescine, spermidine, and spermine
      on purified walls of carrot (Daucus carota L.) cell suspensions were investigated
      by producing ion-exchange isotherms and comparing them with the behavior of Na+,
      Mg2+, and Ca2+. The cation exchange capacity of the carrot cell walls was 0.8
      equivalent kg-1 dry matter, and the ionic selectivity sequence of the walls for
      polyamines followed the sequence spermine4+ > spermidine3+ [almost equal to] Ca2+
      > putrescine2+. The polyamines were subjected to only electroselectivity and
      probably did not induce any favorable supramolecular conformation of pectin like
      the one induced by Ca2+. Triangular ion exchanges were also performed with three
      diamines: ethanediamine, butanediamine, and octanediamine. The shorter the
      diamine, the higher the total adsorption and selectivity of the exchange. The
      lower selectivity of the cell wall for putrescine was partly attributed to its
      inability to access and displace Ca2+ from higher affinity sites within dimerized
      pectic sequences. The polyamine adsorption and exchange on pectic sequences could
      result in pectic signal modulation in pathogenesis and in differentiation.

PMID- 12223614
TI  - A Competitive Enzyme-Linked Immunosorbent Assay to Quantify Acetaldehyde-Protein
      Adducts That Accumulate in Dry Seeds during Aging.
AB  - A competitive enzyme-linked immunosorbent assay (ELISA) was developed to quantify
      endogenous acetaldehyde-protein adducts (APAs) produced in plant seeds at low
      acetaldehyde concentrations without exogenous reducing agents. The key point of
      this technique is the use of a gelatin-acetaldehyde adduct, which is synthesized
      under 1 mM acetaldehyde and 10 mM NaCNBH3, to pre-coat plate wells to obtain the
      proper binding parameters for the quantification of APA in seed proteins.
      Compared with the traditional, direct ELISA method, the competitive one has
      higher sensitivity and less background. Using competitive ELISA, we determined
      the accumulation of endogenous APAs in seeds in relation to the loss of seed
      viability. Lettuce seeds were exposed to 2 mM gaseous acetaldehyde during storage
      for 30 or 45 d; the relative humidity and temperature of storage were studied
      independently. Viability decreased only in acetaldehyde-treated seeds, as either
      the temperature or the relative humidity increased. A loss in viability was
      accompanied by an increase in the accumulation of APA. The APA content also
      increased as viability decreased in five species of seeds, which were aged
      naturally without exposure to acetaldehyde. It is suggested that the modification
      of functional seed proteins with endogenously evolved acetaldehyde may be an
      important cause of seed aging.

PMID- 12223615
TI  - Natural Senescence of Pea Leaves (An Activated Oxygen-Mediated Function for
      Peroxisomes).
AB  - We studied the activated oxygen metabolism of peroxisomes in naturally and dark
      induced senescent leaves of pea (Pisum sativum L.). Peroxisomes were purified
      from three different types of senescent leaves and the activities of different
      peroxisomal and glyoxysomal enzymes were measured. The activities of the O2-- and
      H2O2-producing enzymes were enhanced by natural senescence. Senescence also
      produced an increase in the generation of active oxygen species (O2- and H2O2) in
      leaf peroxisomes and in the activities of two glyoxylate-cycle marker enzymes. A
      new fraction of peroxisomes was detected at an advanced stage of dark-induced
      senescence. Electron microscopy revealed that this new peroxisomal fraction
      varied in size and electron density. During senescence, the constitutive Mn
      superoxide dismutase (SOD) activity of peroxisomes increased and two new CuZn
      SODs were induced, one of which cross-reacted with an antibody against
      glyoxysomal CuZn- SOD. This fact and the presence of glyoxylate-cycle enzymes
      support the idea that foliar senescence is associated with the transition of
      peroxisomes into glyoxysomes. Our results indicate that natural senescence causes
      the same changes in peroxisome-activated oxygen metabolism as dark-induced
      senescence, and reinforce the hypothesis of an effective role of peroxisomes and
      their activated oxygen metabolism in this stage of the life cycle.

PMID- 12223616
TI  - Sugar-Dependent Gibberellin-Induced Chalcone Synthase Gene Expression in Petunia
      Corollas.
AB  - The induction of anthocyanin synthesis and anthocyanin biosynthetic gene
      expression in detached petunia (Petunia hybrida) corollas by gibberellic acid
      (GA3) requires sucrose. Neither sucrose nor GA3 alone can induce these processes.
      We found that GA3 enhances sucrose uptake by 20 to 30%, and we tested whether
      this is the mechanism by which the hormone induces gene expression. Changing the
      intracellular level of sucrose with the inhibitors p-chloromercuribenzenesulfonic
      acid and vanadate did not inhibit the induction of chalcone synthase gene (chs)
      expression by GA3. Growing detached corollas in various sucrose concentrations
      did not affect the induction of the gene but did affect its level of expression
      and the level of anthocyanin accumulated. Only metabolic sugars promoted GA3
      induced anthocyanin accumulation. Mannitol and sorbitol had no effect and 3-O
      methylglucose only slightly promoted chs expression and anthocyanin accumulation.
      Our results do not support the suggestion that sugars act as specific signals in
      the activation of anthocyanin biosynthetic gene expression during petunia corolla
      development. We suggest that sugars are essential as general sources of
      carbohydrates for carbon metabolism, upon which the induction of pigmentation is
      dependent.

PMID- 12223618
TI  - High Photosynthetic Capacity in a Shade-Tolerant Crassulacean Acid Metabolism
      Plant (Implications for Sunfleck Use, Nonphotochemical Energy Dissipation, and
      Susceptibility to Photoinhibition).
AB  - Aechmea magdalenae Andre ex Baker, a constitutive Crassulacean acid metabolism
      (CAM) plant from the shaded Panamanian rain forest understory, has a maximum
      photosynthesis rate 2 to 3 times that of co-occurring C3 species and a limited
      potential for photosynthetic acclimation to high light. Chlorophyll fluorescence
      measurements indicated that (a) compared with co-occurring C3 species,
      photosynthetic electron transport in A. magdalenae responded more rapidly to
      light flecks of moderate intensity, attained a higher steady-state rate, and
      maintained a lower reduction state of plastoquinone during light flecks; (b)
      these characteristics were associated with phase III CO2 fixation of CAM; (c)
      when grown in full sun, A. magdalenae was chronically photoinhibited despite a
      remarkably high nonphotochemical quenching capacity, indicating a large potential
      for photoprotection; and (d) the degree of photoinhibition was inversely
      proportional to the length of phase III. Results from the light fleck studies
      suggest that understory A. magdalenae plants can make more efficient use of sun
      flecks for leaf carbon gain over most of the day than co-occurring C3 species.
      The association between the duration of phase III and the degree of
      photoinhibition for A. magdalenae in high light is discussed in relation to the
      limited photosynthetic plasticity in this species.

PMID- 12223617
TI  - Acetaldehyde Is a Causal Agent Responsible for Ethanol-Induced Ripening
      Inhibition in Tomato Fruit.
AB  - Inhibition of tomato (Lycopersicon esculentum Mill.) fruit ripening by
      exogenously applied ethanol was shown to be caused by elevated endogenous levels
      of acetaldehyde (AA). Exposure of excised pericarp discs of mature-green tomato
      fruit to ethanol or AA vapors produced elevated levels of both compounds in the
      tissue, but only the levels of AA were associated with ripening inhibition.
      Ripening inhibition was dependent on both the applied concentration and the
      duration of exposure. Discs treated with inhibitory levels of AA had levels of
      ethanol that were elevated but below that associated with inhibition of ripening.
      The in vivo activity of alcohol dehydrogenase was inhibited 40 to 60% by 4
      methylpyrazole (4-MP), a competitive inhibitor of this enzyme. The inhibitory
      effect of ethanol on ripening was reduced by the simultaneous application of 4
      MP. Tissue treated with 4-MP plus AA vapors had higher endogenous levels of AA
      and ripening was inhibited longer than in tissue without 4-MP. The tissue AA
      level resulting from ethanol or AA application appears to be the critical
      determinant of ripening inhibition.

PMID- 12223619
TI  - Differential Ammonia-Elicited Changes of Cytosolic pH in Root Hair Cells of Rice
      and Maize as Monitored by 2[prime],7[prime]-bis-(2-Carboxyethyl)-5 (and -6)
      Carboxyfluorescein-Fluorescence Ratio.
AB  - Intact hair cells of young rice (Oryza sativa L.) and maize roots (Zea mays L.),
      grown without external nitrogen, were specifically loaded with 2[prime],7[prime]
      bis-(2-carboxyethyl)-5 (and -6)-carboxyfluorescein acetoxymethyl ester to monitor
      fluorescence ratio cytosolic pH changes in response to external ammonia
      (NH4+/NH3) application. In neutral media, cytosolic pH of root hairs was 7.15
      [plus or minus] 0.13 (O. sativa) and 7.08 [plus or minus] 0.11 (Z. mays).
      Application of 2 mM ammonia at external pH 7.0 caused a transient cytosolic
      alkalization (7.5 [plus or minus] 0.15 in rice; 7.23 [plus or minus] 0.13 in
      maize). Alkalization increased with an increase of external pH; no pH changes
      occurred at external pH 5.0. The influx of 13N-labeled ammonia in both plant
      species did not differ between external pH 5.0 and 7.0 but increased
      significantly with higher pH. Pretreatment with 1 mM 1-methionine sulfoximine
      significantly reduced the ammonia-elicited pH increase in rice but not in maize.
      Application of 2 mM methylammonia only caused a cytosolic pH increase at high
      external pH; the increase in both species compared with the ammonia-elicited
      alkalization in 1-methionine sulfoximine-treated roots. The differential effects
      indicate that cytosolic alkalization derived from (a) NH3 protonation after
      passive permeation of the plasma membrane and, particularly in rice, (b)
      additional proton consumption via the glutamine synthetase/glutamate synthase
      cycle.

PMID- 12223620
TI  - Reduction of Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase by Antisense RNA in
      the C4 Plant Flaveria bidentis Leads to Reduced Assimilation Rates and Increased
      Carbon Isotope Discrimination.
AB  - Transgenic Flaveria bidentis (a C4 species) plants with an antisense gene
      directed against the mRNA of ribulose-1,5-bisphosphate carboxylase/oxygenase
      (Rubisco) were used to examine the relationship between the CO2 assimilation
      rate, Rubisco content, and carbon isotope discrimination. Reduction in the amount
      of Rubisco in the transgenic plants resulted in reduced CO2 assimilation rates
      and increased carbon isotope discrimination of leaf dry matter. The H2O exchange
      was similar in transgenic and wild-type plants, resulting in higher ratios of
      intercellular to ambient CO2 partial pressures. Carbon isotope discrimination was
      measured concurrently with CO2 and H2O exchange on leaves of the control plants
      and T1 progeny with a 40% reduction in Rubisco. From the theory of carbon isotope
      discrimination in the C4 species, we conclude that the reduction in the Rubisco
      content in the transgenic plants has led to an increase in bundle-sheath CO2
      concentration and CO2 leakage from the bundle sheath; however, some down
      regulation of the C4 cycle also occurred.

PMID- 12223621
TI  - A [beta]-Amylase in Potato Tubers Is Induced by Storage at Low Temperature.
AB  - A new starch-degrading enzyme activity is induced by storage of potato (Solanum
      tuberosum L.) tubers at low temperatures (L. Hill, R. Reimholz, R. Schroder, T.H.
      Nielsen, M. Stitt [1996] Plant Cell Environ 14: 1223-1237). The cold-induced
      activity was separated from other amylolytic activities in zymograms based on
      iodine staining of polyacrylamide gels containing amylopectin. A similar band of
      activity was detected at normal growth temperatures in leaves, stems, and growing
      tubers but was present only at low activity in warm-stored tubers. The cold
      induced enzyme was separated by ion-exchange chromatography from other amylolytic
      activities. It has a broad neutral pH optimum. Characterization of its hydrolytic
      activity with different substrates showed that the cold-induced activity is a
      [beta]-amylase present at low activity in tubers stored at 20[deg]C and induced
      progressively when temperatures are decreased to 5 and 3[deg]C. The first clear
      induction of [beta]-amylase activity was observed within 3 d of storage at
      3[deg]C, and the activity increased 4- to 5-fold within 10 d. The possible
      involvement of the cold-induced [beta]-amylase in sugar accumulation during cold
      storage is discussed.

PMID- 12223622
TI  - Identification and Characterization of Linoleic Acid as an Endogenous Modulator
      of in Vitro N-1-Naphthylphthalamic Acid Binding.
AB  - An endogenous inhibitor of the in vitro binding of the phytotropin N-1
      naphthylphthalamic acid to microsomal membranes was detected in extracts prepared
      from etiolated pea (Pisum sativum L.) epicotyls. Following extensive
      purification, the inhibitor was identified as linoleic acid. Authentic linoleic
      acid inhibited N-1-naphthylphthalamic acid binding noncompetitively in a dose
      dependent manner, exhibiting a 50% inhibitory concentration of approximately 24
      ([mu]M. Using a variety of fatty acids and their derivatives, this inhibition was
      found to exhibit strict structural requirements, with both linoleic and linolenic
      acids being the most inhibitory. A variety of membrane-solubilizing detergents
      elicited no such inhibitory activity when tested at equivalent concentrations.
      The possible physiological significance of this interaction is discussed and it
      is proposed that linoleic acid serves as an intracellular modulator of
      phytotropin binding and therefore polar auxin transport.

PMID- 12223623
TI  - Al Partitioning Patterns and Root Growth as Related to Al Sensitivity and Al
      Tolerance in Wheat.
AB  - Studies of Al partitioning and accumulation and of the effect of Al on the growth
      of intact wheat (Triticum aestivum L.) roots of cultivars that show differential
      Al sensitivity were conducted. The effects of various Al concentrations on root
      growth and Al accumulation in the tissue were followed for 24 h. At low external
      Al concentrations, Al accumulation in the root tips was low and root growth was
      either unaffected or stimulated. Calculations based on regression analysis of
      growth and Al accumulation in the root tips predicted that 50% root growth
      inhibition in the Al-tolerant cv Atlas 66 would be attained when the Al
      concentrations were 105 [mu]M in the nutrient solution and 376.7 [mu]g Al g-1 dry
      weight in the tissue. In contrast, in the Al-sensitive cv Tam 105, 50% root
      growth inhibition would be attained when the Al concentrations were 11 [mu]M in
      the nutrient solution and 546.2 [mu]g Al g-1 dry weight in the tissue. The data
      support the hypotheses that differential Al sensitivity correlates with
      differential Al accumulation in the growing root tissue, and that mechanisms of
      Al tolerance may be based on strategies to exclude Al from the root meristems.

PMID- 12223624
TI  - Distinction between Endoplasmic Reticulum-Type and Plasma Membrane-Type Ca2+
      Pumps (Partial Purification of a 120-Kilodalton Ca2+-ATPase from Endomembranes).
AB  - Two biochemical types of Ca2+-pumping ATPases were distinguished in membranes
      that were isolated from carrot (Daucus carota) suspension-cultured cells. One
      type hydrolyzed GTP nearly as well as ATP, was stimulated by calmodulin, and was
      resistant to cyclopiazonic acid. This plasma membrane (PM)-type pump was
      associated with PMs and endomembranes, including vacuolar membranes and the
      endoplasmic reticulum (ER). Another pump ("ER-type") that was associated mainly
      with the ER hydrolyzed ATP preferentially, was insensitive to calmodulin, and was
      inhibited partially by cyclopiazonic acid, a blocker of the animal
      sarcoplasmic/ER Ca2+ pump. Oxalate stimulation of Ca2+ accumulation by ER-type,
      but not PM-type, pump(s) indicated a separation of the two types on distinct
      compartments. An endomembrane 120-kD Ca2+ pump was partially purified by
      calmodulin-affinity chromatography. The purified polypeptide bound calmodulin
      reacted with antibodies to a calmodulin-stimulated Ca2+ pump from cauliflower and
      displayed [32P]phosphoenzyme properties that are characteristic of PM-type Ca2+
      pumps. The purified ATPase corresponded to a phosphoenzyme and a 120-kD
      calmodulin-binding protein on endomembranes. Another PM-type pump was suggested
      by a 127-kD PM-associated protein that bound calmodulin. Thus, both ER- and PM
      type Ca2+ pumps coexist in most plant tissues, and each type can be distinguished
      from another by a set of traits, even in partially purified membranes.

PMID- 12223625
TI  - Characterization of the Glycerolipid Composition and Biosynthetic Capacity of Pea
      Root Plastids.
AB  - The glycerolipid composition of pea (Pisum sativum L.) root plastids and their
      capacity to synthesize glycerolipids from [UL-14C]glycerol-3-phosphate were
      determined. Pea root plastids primarily consist of monogalactosyldiacylglycerol,
      triacylglycerol, phosphatidylcholine, digalactosyldiacylglycerol, and
      diacylglycerol. Maximum rates of total glycerolipid biosynthesis were obtained in
      the presence of 2.4 mM glycerol-3-phosphate, 15 mM KHCO3, 0.2 mM sodium-acetate,
      0.5 mM each of NADH and NADPH, 0.05 mM coenzyme A, 2 mM MgCl2, 1 mM ATP, 0.1 M
      Bis-Tris propane (pH 7.5), and 0.31 M sorbitol. Glycerolipid biosynthesis was
      completely dependent on exogenously supplied ATP, coenzyme A, and a divalent
      cation, whereas the remaining cofactors improved their activity from 1.3- to 2.4
      fold. Radioactivity from glycerol-3-phosphate was recovered predominantly in
      phosphatidic acid, phosphatidylglycerol, diacylglycerol, and triacylglycerol with
      lesser amounts in phosphatidylcholine and monoacylglycerol. The proportions of
      the various radiolabeled lipids that accumulated were dependent on the pH and the
      concentration of ATP and glycerol-3-phosphate. The data presented indicate that
      pea root plastids can synthesize almost all of their component glycerolipids and
      that glycerolipid biosynthesis is tightly coupled to de novo fatty acid
      biosynthesis. pH and the availability of ATP may have important roles in the
      regulation of lipid biosynthesis at the levels of phosphatidic acid phosphatase
      and in the reactions that are involved in phosphatidylglycerol and
      triacylglycerol biosynthesis.

PMID- 12223626
TI  - Xylem Sap pH Increase: A Drought Signal Received at the Apoplastic Face of the
      Guard Cell That Involves the Suppression of Saturable Abscisic Acid Uptake by the
      Epidermal Symplast.
AB  - Drought increased the pH of Commelina communis xylem sap from 6.1 to 6.7.
      Conductances of transpiring leaves were 50% lower in pH 7.0 than in pH 6.0
      buffers, but bulk leaf abscisic acid (ABA) concentration and shoot water status
      were unaffected by pH. Stomatal apertures of isolated abaxial epidermis incubated
      on simple buffers increased with external pH, so in vivo this must be overridden
      by alternative pH effects. Reductions in leaf transpiration rate at pH 7.0 were
      dependent on the presence of 10-8 mol dm-3 ABA in the xylem stream. We inferred
      that at pH 7.0 leaf apoplastic ABA concentrations increased: pH did not affect
      distributions of ABA among leaf tissues, but isolated epidermis and mesophyll
      tissue took up more 3H-ABA from pH 6.0 than from pH 7.0 buffers. The apoplastic
      ABA increase at pH 7.0 may result from reduced symplastic sequestration. A
      portion of 3H-ABA uptake by the epidermis was saturable at pH 6.0 but not at pH
      7.0. An ABA uptake carrier may contribute to ABA sequestration by the leaf
      symplast of well-watered plants, and its inactivity at pH 7.0 may favor
      apoplastic ABA accumulation in draughted plants. Effects of external pH on
      stomatal apertures in the isolated epidermis indicate that published data
      supporting a role for internal guard cell ABA receptors should be reassessed.

PMID- 12223627
TI  - Hypoosmotic Shock Induces Increases in Cytosolic Ca2+ in Tobacco Suspension
      Culture Cells.
AB  - Hypoosmotic shock treatment increased cytosolic Ca2+ ion concentration
      ([Ca2+]cyt) in tobacco (Nicotiana tabacum) suspension-culture cells. [Ca2+]cyt
      measurements were made by genetically transforming these cells to express
      apoaequorin and by reconstituting the Ca2+-dependent photoprotein, aequorin, in
      the cytosol by incubation with chemically synthesized coelenterazine. Measurement
      of Ca2+-dependent luminescence output thus allowed the direct monitoring of
      [Ca2+]cyt changes. When cells were added to a hypoosmotic medium, a biphasic
      increase in [Ca2+]cyt was observed; an immediate small elevation (phase 1) was
      observed first, followed by a rapid, large elevation (phase 2). Phase 1 [Ca2+]cyt
      was stimulated by the V-type ATPase inhibitor bafilomycin A1. Phase 2 was
      inhibited by the protein kinase inhibitor K-252a and required the continued
      presence of the hypoosmotic stimulus to maintain it. Although Ca2+ in the medium
      was needed to produce phase 2, it was not needed to render the cells competent to
      the hypoosmotic stimulus. If cells were subject to hypoosmotic shock in Ca2+-
      depleted medium, increases in luminescence could be induced up to 20 min after
      the shock by adding Ca2+ to the medium. These data suggest that hypoosmotic shock
      induced [Ca2+]cyt elevation results from the activity of a Ca2+ channel in the
      plasma membrane or associated hypoosmotic sensing components that require Ca2+-
      independent phosphorylation and a continued stimulus to maintain full activity.

PMID- 12223628
TI  - Water Transport Properties of Roots and Root Cortical Cells in Proton- and Al
      Stressed Maize Varieties.
AB  - Root and root cell pressure-probe techniques were used to investigate the
      possible relationship between Al- or H+-induced alterations of the hydraulic
      conductivity of root cells (LPc) and whole-root water conductivity (LPr) in maize
      (Zea mays L.) plants. To distinguish between H+ and Al effects two varieties that
      differ in H+ and Al tolerance were assayed. Based on root elongation rates after
      24 h in nutrient solution of pH 6.0, pH 4.5, or pH 4.5 plus 50 [mu]M Al, the
      variety Adour 250 was found to be H+-sensitive and Al-tolerant, whereas the
      variety BR 201 F was found to be H+-tolerant but Al-sensitive. No Al-induced
      decrease of root pressure and root cell turgor was observed in Al-sensitive BR
      201 F, indicating that Al toxicity did not cause a general breakdown of membrane
      integrity and that ion pumping to the stele was maintained. Al reduced LPc more
      than LPr in Al-sensitive BR 201 F. Proton toxicity in Adour 250 affected LPr more
      than LPc. In this Al-tolerant variety LPc was increased by Al. Nevertheless, this
      positive effect on LPc did not render higher LPr values. In conclusion, there
      were no direct relationships between Al- or H+-induced decreases of LPr and the
      effects on LPc. To our knowledge, this is the first time that the influence of H+
      and Al on root and root cell water relations has been directly measured by
      pressure-probe techniques.

PMID- 12223629
TI  - Auxin-Induced Epinasty of Tobacco Leaf Tissues (A Nonethylene-Mediated Response).
AB  - Interveinal strips (10 x 1.5 mm) excised from growing tobacco (Nicotiana tabacum
      L. cv Xanthi) leaves curled >300[deg] when incubated for 20 h in 5 to 500 [mu]M
      [alpha]-naphthalene acetic acid or 50 to 500 [mu]M indole-3-acetic acid. Epinasty
      was not induced without auxin or by the auxin analog [beta]-naphthalene acetic
      acid, and less substantial epinasty was induced in midrib and vein segments.
      Auxin treatment increased the length of both surfaces of strips. Curvature
      resulted from greater growth on the adaxial side. Epinastic sensitivity of strips
      to auxin appeared first in the distal third of young leaves (blade 4.5-6.0 cm).
      In older leaves (8-10 and 12-14 cm), the interveinal tissues throughout were
      sensitive, whereas in leaves 16- to 18-cm long, sensitivity was reduced in the
      distal two-thirds. Amino-oxyacetic acid (AOA), an ethylene biosynthesis
      inhibitor, partially inhibited epinasty at 100 [mu]M. However, a poor correlation
      between inhibition of ethylene biosynthesis by AOA and its inhibition of
      curvature and the inability of ethylene to produce epinasty or to reverse the
      effects of AOA suggests that auxin-induced epinasty is not caused by auxin
      induced ethylene production.

PMID- 12223630
TI  - Characterization of a Diffusible Signal Capable of Inducing Defense Gene
      Expression in Tobacco.
AB  - Treatment of tobacco (Nicotiana tabacum) cell-suspension cultures with
      cryptogein, an elicitin protein from Phytophthora cryptogea, resulted in the
      release of a factor(s) that diffused through a 1000-D cutoff dialysis membrane
      and was capable of inducing sesquiterpene cyclase enzyme activity (a key
      phytoalexin biosynthetic enzyme in solanaceous plants) when added to fresh cell
      suspension cultures. The diffusible factor(s) was released from cells over a 20-h
      period and induced a more rapid induction of cyclase enzyme activity than did
      direct treatment of the cultures with pure elicitin protein. The diffusible
      factor also induced a more rapid accumulation of transcripts encoding for
      sesquiterpene cyclase, acidic and basic chitinase, and hsr203 (a putative
      hypersensitive response gene) than did elicitin treatment. The diffusible
      factor(s) was resistant to protease, pectinase, Dnase, and RNase treatments, was
      not extractable into organic solvents, and was not immunoprecipitable when
      challenged with polyclonal antibodies prepared against elicitin protein. The
      diffusible factor(s) could not induce the release of more factor, suggesting that
      it was a terminal signal. These results are consistent with the notion that cells
      directly challenged or stimulated by pathogen-derived elicitors release
      diffusible secondary signal molecules that orchestrate the induction of
      complementary defense responses in neighboring cells.

PMID- 12223631
TI  - The Control of Apical Bud Growth and Senescence by Auxin and Gibberellin in
      Genetic Lines of Peas.
AB  - Pea (Pisum sativum L.) lines G2 (dwarf) and NGB1769 (tall) (Sn Hr) produce
      flowers and fruit under long (LD) or short (SD) days, but senesce only under LD.
      Endogenous gibberellin (GA) levels were inversely correlated with photoperiod
      (over 9-18 h) and senescence: GA20 was 3-fold and GA1 was 10- to 11-fold higher
      in flowering SD G2 shoots, and the vegetative tissues within the SD apical bud
      contained 4-fold higher levels of GA20, as compared with the LD tissues.
      Prefloral G2 plants under both photoperiods had GA1 and GA20 levels similar to
      the flowering plants under LD. Levels of indole-3-acetic acid (IAA) were similar
      in G2 shoots in LD or SD; SD apical bud vegetative tissues had a slightly higher
      IAA content. Young floral buds from LD plants had twice as much IAA as under SD.
      In NGB1769 shoots GA1 decreased after flower initiation only under LD, which
      correlated with the decreased growth potential. We suggest that the higher GA1
      content of G2 and NGB1769 plants under SD conditions is responsible for the
      extended vegetative growth and continued meristematic activity in the shoot apex.
      This and the increased IAA level of LD floral buds may play a role in the
      regulation of nutrient partitioning, since more photosynthate partitions of
      reproductive tissue under LD conditions, and the rate of reproductive development
      in LD peas is faster than under SD.

PMID- 12223632
TI  - Accumulation of Zeaxanthin in Abscisic Acid-Deficient Mutants of Arabidopsis Does
      Not Affect Chlorophyll Fluorescence Quenching or Sensitivity to Photoinhibition
      in Vivo.
AB  - Abscisic acid (ABA)-deficient mutants of Arabidopsis do not synthesize the epoxy
      xanthophylls antheraxanthin, violaxanthin, or neoxanthin. However, thylakoid
      membranes from these mutants contain 3-fold more zeaxanthin than wild-type
      plants. This increase in zeaxanthin occurs as a stoichiometric replacement of the
      missing violaxanthin and neoxanthin within the pigment-protein complexes of both
      photosystem I and photosystem II (PSII). The retention of zeaxanthin in the dark
      by ABA-deficient mutants sensitizes the leaves to the development of
      nonphotochemical quenching (NPQ) during the first 2 to 4 min following a dark
      light transition. However, the increase in pool size does not result in any
      increase in steady-state NPQ. When we exposed wild-type and ABA-deficient mutants
      leaves to twice growth irradiance, the mutants developed lower maximal NPQ but
      suffered similar photoinhibition to wildtype, measured both as a decline in the
      ratio of variable to maximal fluorescence and as a loss of functional PSII
      centers from oxygen flash yield measurements. These results suggest that only a
      few of the zeaxanthin molecules present within the light-harvesting antenna of
      PSII may be involved in NPQ and neither the accumulation of a large pool of
      zeaxanthin within the antenna of PSII nor an increase in conversion of
      violaxanthin to zeaxanthin will necessarily enhance photoprotective energy
      dissipation.

PMID- 12223633
TI  - Molecular Genetic Evidence of the Ability of Alternative Oxidase to Support
      Respiratory Carbon Metabolism.
AB  - With the cytochrome pathway inhibited, AOX was able to support considerable
      growth of cultured tobacco (Nicotiana tabacum cv Petit Havana SR1) cells but the
      efficiency of carbon utilization decreased dramatically. Antisense cells with
      decreased AOX protein did not grow, whereas sense cells with elevated AOX protein
      had higher growth and respiration rates than the wild type. In antisense cells a
      large accumulation of pyruvate resulted in aerobic ethanolic fermentation.

PMID- 12223634
TI  - Molecular Genetics of Crassulacean Acid Metabolism.
AB  - Most higher plants assimilate atmospheric CO2 through the C3 pathway of
      photosynthesis using ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco).
      However, when CO2 availability is reduced by environmental stress conditions, the
      incomplete discrimination of CO2 over O2 by Rubisco leads to increased
      photorespiration, a process that reduces the efficiency of C3 photosynthesis. To
      overcome the wasteful process of photorespiration, approximately 10% of higher
      plant species have evolved two alternate strategies for photosynthetic CO2
      assimilation, C4 photosynthesis and Crassulacean acid metabolism. Both of these
      biochemical pathways employ a "CO2 pump" to elevate intracellular CO2
      concentrations in the vicinity of Rubisco, suppressing photorespiration and
      therefore improving the competitiveness of these plants under conditions of high
      light intensity, high temperature, or low water availability. This CO2 pump
      consists of a primary carboxylating enzyme, phosphoenolpyruvate carboxylase. In
      C4 plants, this CO2-concentrating mechanism is achieved by the coordination of
      two carboxylating reactions that are spatially separated into mesophyll and
      bundle-sheath cell types (for review, see R.T. Furbank, W.C. Taylor [1995] Plant
      Cell 7: 797-807;M.S.B. Ku, Y. Kano-Murakami, M. Matsuoka [1996] Plant Physiol
      111: 949-957). In contrast, Crassulacean acid metabolism plants perform both
      carboxylation reactions within one cell type, but the two reactions are separated
      in time. Both pathways involve cell-specific changes in the expression of many
      genes that are not present in C3 plants.

PMID- 12223635
TI  - Control of Mitosis by Phytochrome and a Blue-Light Receptor in Fern Spores.
AB  - The first mitosis in spores of the fern A. capillus-veneris was observed under a
      microscope equipped with Nomarski optics with irradiation from a safelight at 900
      nm, and under a fluorescent microscope after staining with 4[prime],6-diamidino-2
      phenylindole. During imbibition the nucleus remained near one corner of each
      tetrahedron-shaped dormant spore, and asymmetric cell division occurred upon
      brief irradiation with red light. This red light-induced mitosis was
      photoreversibly prevented by subsequent brief exposure to far-red light and was
      photo-irreversibly prevented by brief irradiation with blue light. However,
      neither far-red nor blue light affected the germination rate when spores were
      irradiated after the first mitosis. Therefore, the first mitosis in the spores
      appears to be the crucial step for photoinduction of spore germination.
      Furthermore, experiments using a microbeam of red or blue light demonstrated that
      blue light was effective only when exposed to the nucleus, and no specific
      intracellular photoreceptive site for red light was found in the spores.
      Therefore, phytochrome in the far-red absorbing form induces the first mitosis in
      germinating spores but prevents the subsequent mitosis in protonemata, whereas a
      blue-light receptor prevents the former but induces the latter.

PMID- 12223636
TI  - Expression of an Aspartate Kinase Homoserine Dehydrogenase Gene Is Subject to
      Specific Spatial and Temporal Regulation in Vegetative Tissues, Flowers, and
      Developing Seeds.
AB  - Although the regulation of amino acid synthesis has been studied extensively at
      the biochemical level, it is still not known how genes encoding amino acid
      biosynthesis enzymes are regulated during plant development. In the present
      report, we have used the [beta]-glucuronidase (GUS) reporter gene to study the
      regulation of expression of an Arabidopsis thaliana aspartate kinase-homoserine
      dehydrogenase (AK/HSD) gene in transgenic tobacco plants. The polypeptide encoded
      by the AK/HSD gene comprises two linked key enzymes in the biosynthesis of
      aspartate-family amino acids. AK/HSD-GUS gene expression was highly stimulated in
      apical and lateral meristems, lateral buds, young leaves, trichomes, vascular and
      cortical tissues of growing stems, tapetum and other tissues of anthers, pollen
      grains, various parts of the developing gynoecium, developing seeds, and, in some
      transgenic plants, also in stem and leaf epidermal trichomes. AK/HSD-GUS gene
      expression gradually dimished upon maturation of leaves, stems, floral tissues,
      and embryos. GUS expression was relatively low in roots. During seed development,
      expression of the AK/HSD gene in the embryo was coordinated with the initiation
      and onset of storage protein synthesis, whereas in the endosperm it was
      coordinated with the onset of seed desiccation. Upon germination, AK/HSD-GUS gene
      expression in the hypocotyl and the cotyledons was significantly affected by
      light. The expression pattern of the A. thaliana AK/HSD-GUS reporter gene
      positively correlated with the levels of aspartate-family amino acids and was
      also very similar to the expression pattern of the endogenous tobacco AK/HSD mRNA
      as determined by in situ hybridization.

PMID- 12223638
TI  - Evidence of Phytoalexins in Cucumber Leaves Infected with Powdery Mildew
      following Treatment with Leaf Extracts of Reynoutria sachalinensis.
AB  - Phenolic compounds extracted from cucumber (Cucumis sativus L.) leaves were
      separated and analyzed for their differential presence and fungitoxicity in
      relation to a prophylactic treatment with Milsana (Compo, Munster, Germany)
      against powdery mildew (Sphaerotheca fuliginea). Based on our extraction and
      purification procedures, at least eight separate phenolic compounds with
      antifungal activity were identified as intrinsic components of cucumber plants.
      Of these compounds, six displayed a significant increase in concentration as a
      result of elicitation with Milsana, this being particularly evident when the
      plant was stressed by the pathogen. The combined amounts of these antifungal
      compounds in treated plants was nearly five times the level found in control
      plants. One week after Milsana application, some of the antifungal compounds
      obtained through hydrolysis of their glycosidic links were also detected in their
      free form, indicating that they are likely liberated from conjugated phenolics by
      enzymatic hydrolysis in planta. To our knowledge, these results provide the first
      direct evidence that cucumber plants produce elevated levels of phytoalexins in
      response to an eliciting treatment after infection.

PMID- 12223637
TI  - Differential Expression and Turnover of the Tomato Polyphenol Oxidase Gene Family
      during Vegetative and Reproductive Development.
AB  - Polyphenol oxidases (PPOs) are encoded by a highly conserved, seven-member gene
      family clustered within a 165-kb locus on chromosome 8 of tomato (Lycopersicon
      esculentum). Using gene-specific probes capable of differentiating between PPO
      A/C, PPO B, PPO D, and PPO E/F, we examined the spatial and temporal expression
      of this gene family during vegetative and reproductive development. RNA blots and
      in situ hybridization using these probes showed that although PPO expression is
      primarily confined to early stages of development, the steady-state mRNA levels
      of these genes are subject to complex patterns of spatial and temporal regulation
      in vegetative and reproductive organs. Young tomato leaves and flowers possess
      the most abundant PPO transcripts. PPO B is the most abundant in young leaves,
      whereas in the inflorescence PPO B and E/F transcripts are dominant. Differential
      expression of PPOs is also observed in various trichome types. PPO A/C are
      specifically expressed in type I and type IV trichomes. In contrast, PPO D is
      only expressed in type VI trichomes. Type I, IV, and VI trichomes possess PPO E/F
      transcripts. Immunolocalization verified the translational activity of PPOs
      identified by in situ hybridization and suggested cell-type-specific,
      developmentally programmed PPO turnover. In addition, immunolocalization
      demonstrated the accumulation of PPO in specific idioblast cells of stems,
      leaves, and fruits.

PMID- 12223639
TI  - Sucrose-to-Starch Metabolism in Tomato Fruit Undergoing Transient Starch
      Accumulation.
AB  - Immature green tomato (Lycopersicon esculentum) fruits undergo a period of
      transient starch accumulation characterized by developmental changes in the
      activities of key enzymes in the sucrose (Suc)-to-starch metabolic pathway.
      Activities of Suc synthase, fructokinase, ADP-glucose (Glc) pyrophosphorylase,
      and soluble and insoluble starch synthases decline dramatically in parallel to
      the decrease in starch levels in the developing fruit. Comparison of "maximal" in
      vitro activities of the enzymes in the Suc-to-starch pathway suggests that these
      same enzymes are limiting to the rate of starch accumulation. In contrast,
      activities of invertase, UDP-Glc pyrophosphorylase, nucleoside diphosphate
      kinase, phosphoglucoisomerase, and phosphoglucomutase do not exhibit dramatic
      decreases in activity and appear to be in excess of starch accumulation rates.
      Starch accumulation is spatially localized in the inner and radial pericarp and
      columella, whereas the outer pericarp and seed locule contain little starch. The
      seed locule is characterized by lower activities of Suc synthase, UDP-Glc
      pyrophosphorylase, phosphoglucomutase, ADP-Glc pyrophosphorylase, and soluble and
      insoluble starch synthases. The outer pericarp exhibits comparatively lower
      activities of ADP-Glc pyrophosphorylase and insoluble starch synthase only. These
      data are discussed in terms of the developmental and tissue-specific coordinated
      control of Suc-to-starch metabolism.

PMID- 12223640
TI  - Distribution and Activity of the Plasma Membrane H+-ATPase in Mimosa pudica L. in
      Relation to Ionic Fluxes and Leaf Movements.
AB  - Plasma membrane H+-ATPase was immunolocalized in several cell types of the
      sensitive plant Mimosa pudica L., and transmembrane potentials were measured on
      cortical cells. In comparison with the nonspecialized cortical cells of the
      petiole or stem, the proton pump was highly expressed in motor cells. These
      immunological data are in close agreement with electrophysiological data, because
      the active component of the transmembrane potential was low in the nonspecialized
      cortical cells and high in motor cells. Therefore, motor cells contain the plasma
      membrane H+-ATPase required to mediate the ionic fluxes that are involved in
      circadian leaf movements and that are necessary to recover the turgor potential
      that is considerably affected by the large K+ and Cl- efflux associated with
      seismonastic movement. With the exception of sieve tubes, the phloem also had a
      high density of H+-ATPase. This suggests that the recovery of the transmembrane
      ionic gradients (K+ and Cl-), which is affected by various stimuli, is more
      energized by the companion and parenchyma cells than by the sieve elements. In
      addition, at the phloem/cortex interface collocytes displayed the required
      properties for lateral transduction of the action potential toward the pulvinal
      motor cells.

PMID- 12223641
TI  - Developmental Regulation of Lectin and Alliinase Synthesis in Garlic Bulbs and
      Leaves.
AB  - Using a combination of northern blot analysis and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, a detailed study was made of the temporal and
      spatial regulation of garlic (Allium sativum L.) lectins and alliinase throughout
      the life cycle of the plant. The two bulb-specific lectins (ASAI and ASAII),
      which are the most predominant bulb proteins, accumulate exclusively in the
      developing garlic cloves and progressively disappear when the old clove is
      consumed by the plant. On the basis of these observations, ASAI and ASAII can be
      regarded as typical vegetative storage proteins. The leaf-specific lectin (ASAL),
      on the contrary, is specifically synthesized in young leaves and remains present
      until withering. Because ASAL is only a minor protein, it probably fulfills a
      specific function in the plant. Unlike the lectins, alliinase is present in large
      quantities in bulbs as well as in leaves. Moreover, intact alliinase mRNAs are
      present in both tissues as long as they contain living cells. The latter
      observation is in good agreement with the possible involvement of alliinase in
      the plant's defense against pathogens and/or predators.

PMID- 12223642
TI  - Biosynthesis of GA73 Methyl Ester in Lygodium Ferns.
AB  - Biosynthesis of GA73 methyl ester (GA73-Me), the principal antheridiogen in
      Lygodium ferns, was investigated. From the methanol extract of prothallia of
      Lygodium circinnatum, GA25, GA73, GA73-Me, GA88-Me, and a few unknown GA73
      derivatives were detected by GC-MS. Because the presence of GA25 suggests that
      GA24, a direct precursor of GA25, could also be present in L. circinnatum
      prothallia, we used feeding experiments to investigate the possibility that GA24
      is a precursor of GA73-Me. In L. circinnatum prothallia, [2H2]GA24 was converted
      into [2H2]GA73-Me and a trace amount of [2H2]GA9-Me, whereas [2H3]GA9 was
      converted into [2H3]GA9-Me and [2H3]monohydroxy-GA9-Me. Because GA73-Me, GA9-Me,
      and their monohydroxy derivatives had been identified by GC-MS from the culture
      medium of L. circinnatum prothallia, our results suggest that GA73-Me is
      biosynthesized from GA24 via GA73, and that neither GA9 nor GA9-Me is a precursor
      of GA73-Me. Though the possibility had been suggested that GA73-Me is
      biosynthesized from 9,15-cyclo-GA9 (GA103), [2H2]GA103 was not converted into
      [2H2]GA73-Me.

PMID- 12223643
TI  - Purification and Structural and Kinetic Characterization of the
      Pyrophosphate:Fructose-6-Phosphate 1-Phosphotransferase from the Crassulacean
      Acid Metabolism Plant, Pineapple.
AB  - Pyrphosphate-dependent phosphofructokinase (PFP) was purified to electrophoretic
      homogeneity from illuminated pineapple (Ananas comosus) leaves. The purified
      enzyme consists of a single subunit of 61.5 kD that is immunologically related to
      the potato tuber PFP [beta] subunit. The native form of PFP likely consists of a
      homodimer of 97.2 kD, as determined by gel filtration. PFP's glycolytic activity
      was strongly dependent on pH, displaying a maximum at pH 7.7 to 7.9.
      Gluconeogenic activity was relatively constant between pH 6.7 and 8.7. Activation
      by Fru-2,6-bisphosphate (Fru-2,6-P2) was dependent on assay pH. In the glycolytic
      direction, it activated about 10-fold at pH 6.7, but only 2-fold at pH 7.7. The
      gluconeogenic reaction was only weakly affected by Fru-2,6-P2. The true
      substrates for the PFP forward and reverse reactions were Fru-6-phosphate and Mg
      pyrophosphate, and Fru-1,6-P2, orthophosphate, and Mg2+, respectively. The
      results suggest that pineapple PFP displays regulatory properties consistent with
      a pH-based regulation of its glycolytic activity, in which a decrease in
      cytosolic pH caused by nocturnal acidification during Crassulacean acid
      metabolism, which could curtail its activity, is compensated by a parallel
      increase in its sensitivity to Fru-2,6-P2. It is also evident that the [beta]
      subunit alone is sufficient to confer PFP with a high catalytic rate and the
      regulatory properties associated with activation by Fru-2,6-P2.

PMID- 12223644
TI  - Effects of Bafilomycin A1 and Metabolic Inhibitors on the Maintenance of Vacuolar
      Acidity in Maize Root Hair Cells.
AB  - Proton pumps of tonoplast membranes have been studied extensively in vitro, but
      data concerning their regulation in vivo are lacking. Effects of either anoxia,
      or the addition of KCN, 2-deoxy-d-glucose (deoxy-glucose), or bafilomycin-A1
      (BAF) on vacuolar pH of maize (Zea mays L.) root hair cells were followed by
      fluorescence microscopy after loading of 2[prime]7[prime]-bis-(2-carboxyethyl)-5
      (and-6) carboxyfluorescein. Root hair cells were able to maintain vacuolar
      acidity for at least 2 h in the presence of either 10 mM KCN or 50 mM deoxy
      glucose or during anoxia. Treatments with either deoxy-glucose or KCN reduced
      total tissue ATP more than anoxia. ADP accumulated during anoxia and treatment
      with KCN as detected by in vivo 31P-NMR spectroscopy, but not during deoxy
      glucose treatment. With control roots and roots treated with deoxy-glucose, the
      presence of BAF, a specific inhibitor of the V-type ATPase, caused alkalization
      of the vacuolar pH. However, either in the presence of KCN or under anoxic
      conditions, BAF was relatively ineffective in dissipating vacuolar acidity.
      Therefore, under anoxia or in the presence of KCN, unlike the situation with air
      or deoxy-glucose, the V-type ATPase apparently is not required for maintenance of
      vacuolar acidity.

PMID- 12223645
TI  - Enhanced Employment of the Xanthophyll Cycle and Thermal Energy Dissipation in
      Spinach Exposed to High Light and N Stress.
AB  - The involvement of the xanthophyll cycle in photoprotection of N-deficient
      spinach (Spinacia oleracea L. cv Nobel) was investigated. Spinach plants were
      fertilized with 14 mM nitrate (control, high N) versus 0.5 mM (low N) fertilizer,
      and grown under both high- and low-light conditions. Plants were characterized
      from measurements of photosynthetic oxygen exchange and chlorophyll fluorescence,
      as well as carotenoid and cholorophyll analysis. Compared with the high-N plants,
      the low-N plants showed a lower capacity for photosynthesis and a lower
      chlorophyll content, as well as a lower rate of photosystem II photosynthetic
      electron transport and a corresponding increase in thermal energy dissipation
      activity measured as nonphotochemical fluorescence quenching. The low-N plants
      displayed a greater fraction of the total xanthophyll cycle pool as zeaxanthin
      and antheraxanthin at midday, and an increase in the ratio of xanthophyll cycle
      pigments to total chlorophyll. These results indicate that under N limitation
      both the light-collecting system and the photosynthetic rate decrease. However,
      the increased dissipation of excess energy shows that there is excess light
      absorbed at midday. We conclude that spinach responds to N limitation by a
      combination of decreased light collection and increased thermal dissipation
      involving the xanthophyll cycle.

PMID- 12223646
TI  - Shoot versus Root Signal Involvement in Nodulation and Vegetative Growth in Wild
      Type and Hypernodulating Soybean Genotypes.
AB  - Grafting studies involving Williams 82 (normally nodulating) and NOD1-3
      (hypernodulating) soybean (Glycine max [L.] Merr.) lines and Lablab purpureus
      were used to evaluate the effect of shoot and root on nodulation control and
      plant growth. A single- or double-wedge graft technique, with superimposed
      partial defoliation, was used to separate signal control from a photosynthate
      supply effect. Grafting of hypernodulated soybean shoots to roots of Williams 82
      or L. purpureus resulted in increased nodule numbers. Grafting of two shoots to
      one root enhanced root growth in both soybean genotypes, whereas the nodule
      number was a function of shoot genotype but not of the photosynthetic area. In
      double-shoot, single-root-grafted plants, removing trifoliolate leaves from
      either Williams 82 or NOD1-3 shoots decreased root and shoot dry matter,
      attributable to decreased photosynthetic source. Concurrently, Williams 82 shoot
      defoliation increased the nodule number, whereas NOD1-3 shoot defoliation
      decreased the nodule number on both soybean and L. purpureus roots. It was
      concluded that (a) soybean leaves are the dominant site of autoregulatory signal
      production, which controls the nodule number; (b) soybean and L. purpureus have a
      common, translocatable, autoregulatory control signal; (c) seedling vegetative
      growth and nodule number are independently controlled; and (d) two signals,
      inhibitor and promoter, may be involved in controlling legume nodule numbers.

PMID- 12223647
TI  - Abscisic Acid Activates a 48-Kilodalton Protein Kinase in Guard Cell Protoplasts.
AB  - A 49- and a 46-kD Ca2+-independent protein kinase and a 53-kD Ca2+-dependent
      protein kinase were detected in Vicia faba guard cell protoplasts (GCPs) by an in
      gel protein kinase assay using myelin basic protein as a substrate. A 48-kD
      protein kinase designated as abscisic acid (ABA)-responsive protein kinase (ABR
      kinase) appeared when GCPs were treated with ABA. The activation of ABR kinase
      was suppressed by the protein kinase inhibitor staurosporine, indicating that a
      putative activator protein kinase phosphorylates and activates ABR kinase. The
      treatment of GCPs with 1,2-bis(o-aminophenoxy)ethan-N,N,N',N'-tetraacetic acid, a
      calcium chelator, suppressed the activation of ABR kinase, suggesting that an
      influx of extracellular Ca2+ is required for the activation. Staurosporine and K
      252a inhibited both the activity of ABR kinase and the stomatal closure induced
      by ABA treatment of V. faba epidermal peels. These results suggest that ABR
      kinase and its activator kinase may consist of a protein kinase cascade in a
      signal transduction pathway linking ABA perception to stomatal closure. The
      mobility of the 53-kD Ca2+-dependent protein kinase in sodium dodecyl sulfate
      polyacrylamide gel was shifted upon Ca2+ binding to the enzyme, thus exhibiting
      the characteristics of a Ca2+-dependent or calmodulin-like domain protein kinase.
      This kinase may be the activator of ABR kinase.

PMID- 12223648
TI  - The cdc2Ms Kinase Is Differently Regulated in the Cytoplasm and in the Nucleus.
AB  - To study a cyclin-dependent kinase (CDK) from alfalfa (Medicago sativa L.), an
      antibody was raised against the C-terminal 16 amino acids of the protein cdc2aMs.
      The cdc2Ms protein was immunopurified with this antibody and its histone kinase
      activity was measured. The cdc2Ms kinase is activated at the G1/S transition when
      phosphate-starved cells from the G0 phase re-enter the cell cycle and remain
      active as cells transit the S, G2, and M phases, indicating that the same CDK
      regulates all of these phases in alfalfa. In contrast, when cdc2Ms kinase was
      purified by binding to p13suc1, it was active only in the G2 and M phases. In
      immunoblots the C-terminal antibody detected an equal amount of the cdc2Ms
      protein in the cytoplasm and in the nucleus. By indirect immunofluorescence,
      however, the cytoplasmic form of cdc2Ms could not be found in the S phase of the
      cells, indicating that the epitope for the cdc2 antibody is not accessible.
      Binding of putative inhibitor proteins to cdc2 was shown by inactivation of
      purified plant CDK when cell extracts were added. Furthermore, purified CDK
      inhibitors, such as the mouse p27kip1 and the yeast p40sic1, blocked the purified
      plant CDK activity.

PMID- 12223649
TI  - Proteinase Activity during Tracheary Element Differentiation in Zinnia Mesophyll
      Cultures.
AB  - The zinnia (Zinnia elegans) mesophyll cell culture tracheary element (TE) system
      was used to study proteinases active during developmentally programmed cell
      death. Substrate-impregnated gels and single-cell assays revealed high levels of
      proteinase activity in differentiating TEs compared with undifferentiated
      cultured cells and expanding leaves. Three proteinases (145, 28, and 24 kD) were
      exclusive to differentiating TEs. A fourth proteinase (59 kD), although detected
      in extracts from all tissues examined, was most active in differentiating TEs.
      The 28- and 24-kD proteinases were inhibited by thiol proteinase inhibitors,
      leupeptin, and N-[N-(L-3-trans-carboxirane-2-carbonyl)-L-leucyl]-agmatine (E-64).
      The 145- and 59-kD proteinases were inhibited by the serine proteinase inhibitor
      phenylmethylsulfonyl fluoride (PMSF). Extracts from the TE cultures contained
      sodium dodecyl sulfate-stimulated proteolytic activity not detected in control
      cultures. Sodium dodecyl sulfate-stimulated proteolysis was inhibited by
      leupeptin or E-64, but not by PMSF. Other tissues, sucrose-starved cells and
      cotyledons, that contain high levels of proteolytic activity did not contain TE
      specific proteinases, but did contain higher levels of E-64-sensitive activities
      migrating as 36- to 31-kD enzymes and as a PMSF-sensitive 66-kD proteinase.

PMID- 12223650
TI  - Growth, Water Relations, and Accumulation of Organic and Inorganic Solutes in
      Roots of Maize Seedlings during Salt Stress.
AB  - Seedlings of maize (Zea mays L. cv Pioneer 3906), hydroponically grown in the
      dark, were exposed to NaCl either gradually (salt acclimation) or in one step
      (salt shock). In the salt-acclimation treatment, root extension was
      indistinguishable from that of unsalinized controls for at least 6 d at
      concentrations up to 100 mM NaCl. By contrast, salt shock rapidly inhibited
      extension, followed by a gradual recovery, so that by 24 h extension rates were
      the same as for controls, even at 150 mM NaCl. Salt shock caused a rapid decrease
      in root water and solute potentials for the apical zones, and the estimated
      turgor potential showed only a small decline; similar but more gradual changes
      occurred with salt acclimation. The 5-bar decrease in root solute potential with
      salt shock (150 mM NaCl) during the initial 10 min of exposure could not be
      accounted for by dehydration, indicating that substantial osmotic adjustment
      occurred rapidly. Changes in concentration of inorganic solutes (Na+, K+, and Cl
      ) and organic solutes (proline, sucrose, fructose, and glucose) were measured
      during salt shock. The contribution of these solutes to changes in root solute
      potential with salinization was estimated.

PMID- 12223651
TI  - Photosynthetic Electron Transport in Single Guard Cells as Measured by Scanning
      Electrochemical Microscopy.
AB  - Scanning electrochemical microscopy (SECM) is a powerful new tool for studying
      chemical and biological processes. It records changes in faradaic current as a
      microelectrode ([less than equal]7 [mu]m in diameter) is moved across the surface
      of a sample. The current varies as a function of both distance from the surface
      and the surface's chemical and electrical properties. We used SECM to examine in
      vivo topography and photosynthetic electron transport of individual guard cells
      in Tradescantia fluminensis, to our knowledge the first such analysis for an
      intact plant. We measured surface topography at the micrometer level and
      concentration profiles of O2 evolved in photosynthetic electron transport.
      Comparison of topography and oxygen profiles above single stomatal complexes
      clearly showed photosynthetic electron transport in guard cells, as indicated by
      induction of O2 evolution by photosynthetically active radiation. SECM is unique
      in its ability to measure topography and chemical fluxes, combining some of the
      attributes of patch clamping with scanning tunneling microscopy. In this paper we
      suggest several questions in plant physiology that it might address.

PMID- 12223652
TI  - The Regulation of Electron Partitioning between the Cytochrome and Alternative
      Pathways in Soybean Cotyledon and Root Mitochondria.
AB  - The regulation of electron partitioning between the cytochrome (Cyt) and
      alternative pathways in soybean (Glycine max L. cv Ransom) mitochondria in the
      absence of added inhibitors has been studied using the oxygen isotope
      fractionation technique. This regulation can depend on several factors, including
      the amount of alternative oxidase protein, the redox status of the alternative
      oxidase regulatory sulfhydryl-disulfide system, the degree of activation by
      [alpha]-keto acids, and the concentration and redox state of the ubiquinone pool.
      We studied electron partitioning onto the alternative pathway in mitochondria
      isolated from etiolated and light-grown cotyledons and roots to ascertain how
      these factors interact in different tissues. In light-grown cotyledon
      mitochondria there is some partitioning to the alternative pathway in state 4,
      which is increased dramatically by either pyruvate or dithiothreitol. In
      etiolated cotyledon mitochondria, the alternative pathway shows little ability to
      compete for electrons with the Cyt pathway under any circumstances. In root
      mitochondria, control of alternative pathway activity is exercised by both the
      ubiquinone pool and the regulatory sulfhydryl-disulfide system. In addition,
      oxygen isotope fractionation by the Cyt and alternative pathways in mitochondria
      were identical to the fractionation for the respective pathways seen in intact
      tissue, suggesting that residual respiration is not present in the absence of
      inhibitors.

PMID- 12223653
TI  - Thermostability and Photostability of Photosystem II in Leaves of the Chlorina-f2
      Barley Mutant Deficient in Light-Harvesting Chlorophyll a/b Protein Complexes.
AB  - The chlorophyll-b-less chlorina-f2 barley mutant is deficient in the major as
      well as some minor light-harvesting chlorophyll-protein complexes of photosystem
      II (LHCII). Although the LHCII deficiency had relatively minor repercussions on
      the leaf photosynthetic performances, the responses of photosystem II (PSII) to
      elevated temperatures and to bright light were markedly modified. The chlorina-f2
      mutation noticeably reduced the thermostability of PSII, with thermal
      denaturation of PSII starting at about 35[deg]C and 38.5[deg]C in chlorina-f2 and
      in the wild type, respectively. The increased susceptibility of PSII to heat
      stress in chlorina-f2 leaves was due to the weakness of its electron donor side,
      with moderate heat stress causing detachment of the 33-kD extrinsic PSII protein
      from the oxygen-evolving complex. Prolonged dark adaptation of chlorina-f2 leaves
      was also observed to inhibit the PSII donor side. However, weak illumination
      slowly reversed the dark-induced inhibition of PSII in chlorina-f2 and cancelled
      the difference in PSII thermostability observed between chlorina-f2 and wild-type
      leaves. The mutant was more sensitive to photoinhibition than the wild type, with
      strong light stress impairing the PSII donor side in chlorina-f2 but not in the
      wild type. This difference was not observed in anaerobiosis or in the presence of
      3-(3,4-dichlorophenyl)- 1,1-dimethylurea, diuron. The acceptor side of PSII was
      only slightly affected by the mutation and/or the aforementioned stress
      conditions. Taken together, our results indicate that LHCII stabilize the PSII
      complexes and maintain the water-oxidizing system in a functional state under
      varying environmental conditions.

PMID- 12223654
TI  - Dynamics of Acetaldehyde Production during Anoxia and Post-Anoxia in Red Bell
      Pepper Studied by Photoacoustic Techniques.
AB  - Acetaldehyde (AA), ethanol, and CO2 production in red bell pepper (Capsicum annum
      L.) fruit has been measured in a continuous flow system as the fruit was switched
      between 20% O2 and anaerobic conditions. Minimum gas phase concentrations of 0.5
      nL L-1, 10 nL L-1, and 1 mL L-1, respectively, can be detected employing a laser
      based photoacoustic technique. This technique allows monitoring of low production
      rates and transient features in real time. At the start of anaerobic treatment
      respiration decreases by 60% within 0.5 h, whereas AA and ethanol production is
      delayed by 1 to 3 h. This suggests a direct slow-down of the tricarboxylic acid
      cycle and a delayed onset of alcoholic fermentation. Reexposure of the fruit to
      oxygen results in a 2- to 10-fold upsurge in AA production. A short anoxic period
      leads to a sharp transient peak lasting about 40 min, whereas after numerous and
      longer anoxic periods, post-anoxic AA production stays high for several hours.
      High sensitivity of the fruit tissue to oxygen is further evidenced by a sharp
      decrease in post-anoxic AA production upon an early return to anaerobic
      conditions. Ethanol oxidation by the "peroxidatic" action of catalase is proposed
      to account for the immediate post-anoxic AA upsurge.

PMID- 12223655
TI  - Regulation of the Cinnamate 4-Hydroxylase (CYP73A1) in Jerusalem Artichoke Tubers
      in Response to Wounding and Chemical Treatments.
AB  - trans-Cinnamate 4-hydroxylase (C4H) is a plant-specific cytochrome (P450) that is
      encoded by the gene CYP73A and catalyzes the second step of the multibranched
      phenylpropanoid pathway. Increases in C4H activity in response to physical and
      chemical stresses have been well documented, but the mechanism of these increases
      has never been studied in detail. This paper reports on the regulatory mechanism
      controlling C4H activity in Jerusalem artichoke (Helianthus tuberosus) tubers in
      response to wounding and chemical treatments. We compared induction of C4H and
      other P450-catalyzed activities. C4H was moderately induced by chemicals relative
      to other P450s. Increases in enzyme activity, C4H protein, and transcripts were
      quantified and compared in tuber tissue 48 h after wounding and chemical
      treatments. Our data suggest that induction of the enzyme activity results
      primarily from gene activation. Time-course experiments were performed after
      wounding and aminopyrine treatment. Compared with wounded tissues, aminopyrine
      triggered an additional and delayed peak of transcript accumulation. The timing
      of the induced changes in activity, protein, and transcripts confirms that C4H
      induction results primarily from an increase in CYP73A1 mRNA, in both wounded and
      aminopyrine-treated tissues. However, posttranscriptional mechanisms might also
      contribute to the regulation of C4H activity.

PMID- 12223656
TI  - Leaf Respiration in Light and Darkness (A Comparison of Slow- and Fast-Growing
      Poa Species).
AB  - We investigated whether leaf dark respiration (nonphotorespiratory mitochondrial
      CO2 release) is inhibited by light in several Poa species, and whether
      differences in light inhibition between the species are related to differences in
      the rate of leaf net photosynthesis. Four lowland (Poa annua L., Poa compressa
      L., Poa pratensis L., and Poa trivialis L.), one subalpine (Poa alpina L.), and
      two alpine (Poa costiniana Vick. and Poa fawcettiae Vick.) Poa species differing
      in whole plant relative growth rates were grown under identical controlled
      conditions. Nonphotorespiratory mitochondrial CO2 release in the light (Rd) was
      estimated according to the Laisk method. Photosynthesis was measured at ambient
      CO2 partial pressure (35 Pa) and 500 [mu]mol photons m-2 s-1. The rate of
      photosynthesis per unit leaf mass was positively correlated with the relative
      growth rate, with the slow-growing alpine Poa species exhibiting the lowest
      photosynthetic rates. Rates of both Rd and respiration in darkness were also
      substantially lower in the alpine species. Nonphotorespiratory CO2 release in
      darkness was higher than Rd in all species. However, despite some variation
      between the species in the level of light inhibition of respiration, no
      relationship was observed between the level of inhibition and the rate of
      photosynthesis. Similarly, the level of inhibition was not correlated with the
      relative growth rate. Our results support the suggestion that rates of leaf
      respiration in the light are closely associated with rates in darkness.

PMID- 12223657
TI  - Osmotic Stress Suppresses Cell Wall Stiffening and the Increase in Cell Wall
      Bound Ferulic and Diferulic Acids in Wheat Coleoptiles.
AB  - The relationship between the mechanical properties of cell walls and the levels
      of wall-bound ferulic (FA) and diferulic (DFA) acids was investigated in wheat
      (Triticum aestivum L.) coleoptiles grown under osmotic stress (60 mM polyethylene
      glycol [PEG] 4000) conditions. The cell walls of stressed coleoptiles remained
      extensible compared with those of the unstressed ones. The contents of wall-bound
      FA and DFA increased under unstressed conditions, but the increase was
      substantially reduced by osmotic stress. In response to PEG removal, these
      contents increased and reached almost the same levels as those of the unstressed
      coleoptiles. A close correlation was observed between the contents of FA and DFA
      and the mechanical properties of cell walls. The activities of phenylalanine
      ammonia-lyase and tyrosine ammonia-lyase increased rapidly under unstressed
      conditions. Osmotic stress substantially reduced the increases in enzyme
      activities. When PEG was removed, however, the enzyme activities increased
      rapidly. There was a close correlation between the FA levels and enzyme
      activities. These results suggest that in osmotically stressed wheat coleoptiles,
      reduced rates of increase in phenylalanine ammonia-lyase and tyrosine ammonia
      lyase activities suppress phenylpropanoid biosynthesis, resulting in the reduced
      level of wall-bound FA that, in turn, probably causes the reduced level of DFA
      and thereby maintains cell wall extensibility.

PMID- 12223658
TI  - Diurnal Fluctuations in Ethylene Formation in Chenopodium rubrum.
AB  - Ethylene formation was studied in 5- to 6-d-old Chenopodium rubrum seedlings
      under the following light regimes: continuous light (CL), continuous darkness
      (CD), and alternating light/darkness (12 h of each). No significant regular
      oscillations in ethylene formation were found in either the CL or CD groups. In
      the light/dark regime, pronounced diurnal fluctuations in ethylene formation were
      observed. Activity of 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase was
      transiently increased on transfer from light to dark and vice versa. In CL, ACC
      oxidase activity did not change significantly, whereas in CD, it decreased
      continuously after the initial increase. The in vivo levels of ACC and N-malonyl
      ACC (MACC) were constant for the first few hours of darkness, then decreased
      dramatically, but increased again in the light. In constant darkness, the level
      of ACC displayed endogenous rhythm, with minimum values at h 12 and 44, and a
      maximum value at h 32 to 36. The level of MACC in both shoots and roots decreased
      in the CD group until h 12, and then remained constant until h 30 before
      decreasing continuously. We conclude that the photoperiodic regime affects both
      ACC and MACC levels, as well as the conversion of ACC to ethylene. Correlation of
      the described changes in ethylene formation to photoperiodic flower induction is
      discussed.

PMID- 12223659
TI  - Internal Detoxification Mechanism of Al in Hydrangea (Identification of Al Form
      in the Leaves).
AB  - An internal detoxification mechanism for Al was investigated in an Al
      accumulating plant, hydrangea (Hydrangea macrophylla), focusing on Al forms
      present in the cells. The leaves of hydrangea contained as much as 15.7 mmol Al
      kg-1 fresh weight, and more than two-thirds of the Al was found in the cell sap.
      Using 27Al- nuclear magnetic resonance, the dominant peak of Al was observed at a
      chemical shift of 11 to 12 parts per million in both intact leaves and the
      extracted cell sap, which is in good accordance with the chemical shift for the
      1:1 Al-citrate complex. Purification of cell sap by molecular sieve
      chromatography (Sephadex G-10) combined with ion-exclusion chromatography
      indicated that Al in fractions with the same retention time as citric acid
      contributed to the observed 27Al peak in the intact leaves. The molar ratio of Al
      to citric acid in the crude and purified cell sap approximated 1. The structure
      of the ligand chelated with Al was identified to be citric acid. Bioassay
      experiments showed that the purified Al complex from the cell sap did not inhibit
      root elongation of corn (Zea mays L.) and the viability of cells on the root tip
      surface was also not affected. These observations indicate that Al is bound to
      citric acid in the cells of hydrangea leaves.

PMID- 12223660
TI  - Extracellular Matrix Assembly in Diatoms (Bacillariophyceae) (I. A Model of
      Adhesives Based on Chemical Characterization and Localization of Polysaccharides
      from the Marine Diatom Achnanthes longipes and Other Diatoms).
AB  - Extracellular adhesives from the diatoms Achnanthes longipes, Amphora
      coffeaeformis, Cymbella cistula, and Cymbella mexicana were characterized by
      monosaccharide and methylation analysis, lectin-fluorescein isothiocyanate
      localization, and cytochemical staining. Polysaccharide was the major component
      of adhesives formed during cell motility, synthesis of a basal pad, and/or
      production of a highly organized shaft. Hot water-insoluble/hot 0.5 M NaHCO3
      soluble anionic polysaccharides from A. longipes and A. coffeaeformis adhesives
      were primarily composed of galactosyl (64-70%) and fucosyl (32-42%) residues. In
      A. longipes polymers, 2,3-, t-, 3-, and 4-linked/substituted galactosyl, t-, 3-,
      4-, and 2-linked fucosyl, and t- and 2-linked glucuronic acid residues
      predominated. Adhesive polysaccharides from C. cistula were EDTA-soluble,
      sulfated, consisted of 83% galactosyl (4-, 4,6-, and 3,4-linked/substituted) and
      13% xylosyl (t-, 4f/5p-, and 3p-linked/substituted) residues, and contained no
      uronosyl residues. Ulex europaeus agglutinin uniformly localized [alpha](1,2)-L
      fucose units in C. cistula and Achnanthes adhesives formed during motility and in
      the pads of A. longipes. D-Galactose residues were localized throughout the
      shafts of C. cistula and capsules of A. coffeaeformis. D-Mannose and/or D
      glucose, D-galactose, and [alpha](t)-L-fucose residues were uniformly localized
      in the outer layers of A. longipes shafts by Cancavalia ensiformis, Abrus
      precatorius, and Lotus tetragonolobus agglutinin, respectively. A model for
      diatom cell adhesive structure was developed from chemical characterization,
      localization, and microscopic observation of extracellular adhesive components
      formed during the diatom cell-attachment process.

PMID- 12223661
TI  - Extracellular Matrix Assembly in Diatoms (Bacillariophyceae) (II. 2,6
      Dichlorobenzonitrile Inhibition of Motility and Stalk Production in the Marine
      Diatom Achnanthes longipes).
AB  - The cellulose synthesis inhibitor 2,6-dichlorobenzonitrile (DCB) and the DCB
      analogs 2-chloro-6-fluorobenzonitrile, 3-amino-2,6-dichlorobenzonitrile, and 5
      dimethylamino-naphthalene-1-sulfonyl-(3-cyano-2, 4-dichloro)aniline (DCBF)
      inhibited extracellular adhesive production in the marine diatom Achnanthes
      longipes, resulting in a loss of motility and a lack of permanent adhesion. The
      effect was fully reversible upon removal of the inhibitor, and cell growth was
      not affected at concentrations of inhibitors adequate to effectively interrupt
      the adhesion sequence. Video microscopy revealed that the adhesion sequence was
      mediated by the export and assembly of polymers, and consisted of initial
      attachment followed by cell motility and eventual production of permanent
      adhesive structures in the form of stalks that elevated the diatom above the
      substratum. A. longipes adhesive polymers are primarily composed of noncellulosic
      polysaccharides (B.A. Wustman, M.R. Gretz, and K.D. Hoagland [1997] Plant Physiol
      113: 1059-1069). These results, together with the discovery of DCB inhibition of
      extracellular matrix assembly in noncellulosic red algal unicells (S.M. Arad, O.
      Dubinsky, and B. Simon [1994] Phycologia 33: 158-162), indicate that DCB inhibits
      synthesis of noncellulosic extracellular polysaccharides. A fluorescent probe,
      DCBF, was synthesized and shown to inhibit adhesive polymer production in the
      same manner as DCB. DCBF specifically labeled an 18-kD polypeptide isolated from
      a membrane fraction. Inhibition of adhesion by DCB and its analogs provides
      evidence of a direct relationship between polysaccharide synthesis and motility
      and permanent adhesion.

PMID- 12223662
TI  - Reduction of Uroporphyrinogen Decarboxylase by Antisense RNA Expression Affects
      Activities of Other Enzymes Involved in Tetrapyrrole Biosynthesis and Leads to
      Light-Dependent Necrosis.
AB  - We introduced a full-length cDNA sequence encoding tobacco (Nicotiana tabacum)
      uroporphyrinogen III decarboxylase (UROD; EC 4.1.1.37) in reverse orientation
      under the control of a cauliflower mosaic virus 35S promoter derivative into the
      tobacco genome to study the effects of deregulated UROD expression on
      tetrapyrrole biosynthesis. Transformants with reduced UROD activity were
      characterized by stunted plant growth and necrotic leaf lesions. Antisense RNA
      expression caused reduced UROD protein levels and reduced activity to 45% of wild
      type, which was correlated with the accumulation of uroporphyrin(ogen) and with
      the intensity of necrotic damage. Chlorophyll levels were only slightly reduced
      (up to 15%), indicating that the plants sustained cellular damage from
      accumulating photosensitive porphyrins rather than from chlorophyll deficiency. A
      16-h light/8-h dark regime at high-light intensity stimulates the formation of
      leaf necrosis compared with a low-light or a 6-h high-light treatment. Transgenic
      plants grown at high light also showed inactivation of 5-aminolevulinate
      dehydratase and porphobilinogen deaminase, whereas the activity of
      coproporphyrinogen oxidase and the 5-aminolevulinate synthesizing capacity were
      not altered. We conclude that photooxidation of accumulating uroporphyrin(ogen)
      leads to the generation of oxygen species, which destabilizes other enzymes in
      the porphyrin metabolic pathway. This porphyrin-induced necrosis resembles the
      induction of cell death observed during pathogenesis and air pollution.

PMID- 12223663
TI  - Restriction of Chlorophyll Synthesis Due to Expression of Glutamate 1
      Semialdehyde Aminotransferase Antisense RNA Does Not Reduce the Light-Harvesting
      Antenna Size in Tobacco.
AB  - The formation of 5-aminolevulinate is a key regulatory step in tetrapyrrole
      biosynthesis. In higher plants, glutamate 1-semialdehyde aminotransferase (GSA
      AT) catalyzes the last step in the sequential conversion of glutamate to 5
      aminolevulinate. Antisense RNA synthesis for GSA-AT leads to reduced GSA-AT
      protein levels in tobacco (Nicotiana tabacum L.) plants. We have used these
      transgenic plants for studying the significance of chlorophyll (Chl) availability
      for assembly of the light-harvesting apparatus. To avoid interfering
      photoinhibitory stress, plants were cultivated under a low photon flux density of
      70 [mu]mol photons m-2 s-1. Decreased GSA-AT expression does not seem to suppress
      other enzymic steps in the Chl pathway, indicating that reduced Chl content in
      transgenic plants (down to 12% of the wild-type level) is a consequence of
      reduced GSA-AT activity. Chl deficiency correlated with a drastic reduction in
      the number of photosystem I and photosystem II reaction centers and their
      surrounding antenna on a leaf area basis. Different lines of evidence from the
      transgenic plants indicate that complete assembly of light-harvesting pigment
      protein complexes is given preference over synthesis of new reaction center/core
      complexes, resulting in fully assembled photosynthetic units with no reduction in
      antenna size. Photosynthetic oxygen evolution rates and in vivo Chl fluorescence
      showed that GSA-AT antisense plants are photochemically competent. Thus, we
      suggest that under the growth conditions chosen during this study, plants tend to
      maintain their light-harvesting antenna size even under limited Chl supply.

PMID- 12223664
TI  - Amino Acid Utilization in Seeds of Loblolly Pine during Germination and Early
      Seedling Growth (I. Arginine and Arginase Activity).
AB  - The mobilization and utilization of the major storage proteins in loblolly pine
      (Pinus taeda L.) seeds following imbibition were investigated. Most of the seed
      protein reserves were contained within the megagametophyte. Breakdown of these
      proteins occurred primarily following radicle emergence and correlated with a
      substantial increase in the free amino acid pool in the seedling; the majority of
      this increase appeared to be the result of export from the megagametophyte. The
      megagametophyte was able to break down storage proteins and export free amino
      acids in the absence of the seedling. Arginine (Arg) was the most abundant amino
      acid among the principal storage proteins of the megagametophyte and was a major
      component of the free amino acid pools in both the seedling and the
      megagametophyte. The increase in free Arg coincided with a marked increase in
      arginase activity, mainly localized within the cotyledons and epicotyl of the
      seedling. Arginase activity was negligible in isolated seedlings. Experiments
      with phenylphosphorodiamidate, a urease inhibitor, supported the hypothesis that
      arginase participates in Arg metabolism in the seedling. The results of this
      study indicate that Arg could play an important role in the nutrition of loblolly
      pine during early seedling growth.

PMID- 12223665
TI  - Expansins and Internodal Growth of Deepwater Rice.
AB  - The distribution and activity of the cell wall-loosening protein expansin is
      correlated with internodal growth in deepwater rice (Oryza sativa L.). Acid
      induced extension of native cell walls and reconstituted extension of boiled cell
      walls were confined to the growing region of the internode, i.e. to the
      intercalary meristem (IM) and the elongation zone. Immunolocalization by tissue
      printing and immunoblot analysis, using antibody against cucumber expansin 29 as
      a probe, confirmed that rice expansin occurred primarily in the IM and elongation
      zone. Rice expansin was localized mainly around the vascular bundles at the base
      of the IM and along the inner epidermal cell layer surrounding the internodal
      cavity. Submergence greatly promoted the growth of rice internodes, and cell
      walls of submerged internodes extended much more in response to acidification
      than did the cell walls of air-grown internodes. Susceptibility of cell walls to
      added expansin was also increased in submerged internodes, and analysis by
      immunoblotting showed that cell walls of submerged internodes contained more
      expansin than did cell walls of air-grown internodes. Based on these data, we
      propose that expansin is involved in mediating rapid internodal elongation in
      submerged deepwater rice internodes.

PMID- 12223666
TI  - NADP-Malate Dehydrogenase in the C4 Plant Flaveria bidentis (Cosense Suppression
      of Activity in Mesophyll and Bundle-Sheath Cells and Consequences for
      Photosynthesis).
AB  - Flaveria bidentis, a C4 dicot, was transformed with sorghum (a monocot) cDNA
      clones encoding NADP-malate dehydrogenase (NADP-MDH; EC 1.1.1.82) driven by the
      cauliflower mosaic virus 35S promoter. Although these constructs were designed
      for over-expression, many transformants contained between 5 and 50% of normal
      NADP-MDH activity, presumably by cosense suppression of the native gene. The
      activities of a range of other photosynthetic enzymes were unaffected. Rates of
      photosynthesis in plants with less than about 10% of normal activity were reduced
      at high light and at high [CO2], but were unaffected at low light or at [CO2]
      below about 150 [mu]L L-1. The large decrease in maximum activity of NADP-MDH was
      accompanied by an increase in the activation state of the enzyme. However, the
      activation state was unaffected in plants with 50% of normal activity. Metabolic
      flux control analysis of plants with a range of activities demonstrates that this
      enzyme is not important in regulating the steady-state flux through C4
      photosynthesis in F. bidentis. Cosense suppression of gene expression was
      similarly effective in both the mesophyll and bundle-sheath cells. Photosynthesis
      of plants with very low activity of NADP-MDH in the bundle-sheath cells was only
      slightly inhibited, suggesting that the presence of the enzyme in this
      compartment is not essential for supporting maximum rates of photosynthesis.

PMID- 12223667
TI  - Circadian Regulation of Sucrose Phosphate Synthase Activity in Tomato by Protein
      Phosphatase Activity.
AB  - Sucrose phosphate synthase (SPS), a key enzyme in sucrose biosynthesis, is
      regulated by protein phosphorylation and shows a circadian pattern of activity in
      tomato. SPS is most active in its dephosphorylated state, which normally
      coincides with daytime. Applying okadaic acid, a potent protein phosphatase
      inhibitor, prevents SPS activation. More interesting is that a brief treatment
      with cycloheximide, a cytoplasmic translation inhibitor, also prevents the light
      activation of SPS without any effect on the amount of SPS protein. Cordycepin, an
      inhibitor of transcript synthesis and processing, has the same effect. Both of
      these inhibitors also prevent the activation phase of the circadian rhythm in SPS
      activity. Conversely, cycloheximide and cordycepin do not prevent the decline in
      circadian SPS activity that normally occurs at night. These observations indicate
      that SPS phosphatase activity but not SPS kinase activity is controlled, directly
      or indirectly, at the level of gene expression. Taken together, these data imply
      that there is a circadian rhythm controlling the transcription of a protein
      phosphatase that subsequently dictates the circadian rhythm in SPS activity via
      effects on this enzyme's phosphorylation state.

PMID- 12223668
TI  - Functional Consequences of Deletions of the N Terminus of the [epsilon] Subunit
      of the Chloroplast ATP Synthase.
AB  - The [epsilon] subunit of the chloroplast ATP synthase functions in part to
      prevent wasteful ATP hydrolysis by the enzyme. In addition, [epsilon] together
      with the remainder of the catalytic portion of the synthase (CF1) is required to
      block the nonproductive leak of protons through the membrane-embedded component
      of the synthase (CFO). Mutant [epsilon] subunits of the spinach (Spinacia
      oleracea) chloroplast ATP synthase that lack 5, 11, or 20 amino acids from their
      N termini ([epsilon]-[delta]5N, [epsilon]-[delta]11N, and [epsilon]-[delta]20N,
      respectively), were overexpressed as inclusion bodies. Using a procedure that
      resulted in the folding of full-length, recombinant [epsilon] in a biologically
      active form, none of these truncated forms resulted in [epsilon] that inhibited
      the ATPase activity of CF1 deficient in [epsilon], CF1(-[epsilon]). Yet, the
      [epsilon]-[delta]5N and [epsilon]-[delta]11N peptides significantly inhibited the
      ATPase activity of CF1(-[epsilon]) bound to CFO in NaBr-treated thylakoids.
      Although full-length [epsilon] rapidly inhibited the ATPase activity of CF1(
      [epsilon]) in solution or bound to CFO, an extended period was required for the
      truncated forms to inhibit membrane-bound CF1(-[epsilon]). Despite the fact that
      [epsilon]-[delta]5N significantly inhibited the ATPase activity of CF1(
      [epsilon]) bound to CFO, it did not block the proton conductance through CFO in
      NaBr-treated thylakoids reconstituted with CF1(-[epsilon]). Based on selective
      proteolysis and the binding of 8-anilino-1-naphthalene sulfonic acid, each of the
      truncated peptides gained significant secondary structure after folding. These
      results strongly suggest (a) that the N terminus of [epsilon] is important in its
      binding to CF1, (b) that CF0 stabilizes [epsilon] binding to the entire ATP
      synthase, and (c) that the N terminus may play some role in the regulation of
      proton flux through CFO.

PMID- 12223669
TI  - N2 Fixation, Carbon Metabolism, and Oxidative Damage in Nodules of Dark-Stressed
      Common Bean Plants.
AB  - Common beans (Phaseolus vulgaris L.) were exposed to continuous darkness to
      induce nodule senescence, and several nodule parameters were investigated to
      identify factors that may be involved in the initial loss of N2 fixation. After
      only 1 d of darkness, total root respiration decreased by 76% and in vivo
      nitrogenase (N2ase) activity decreased by 95%. This decline coincided with the
      almost complete depletion (97%) of sucrose and fructose in nodules. At this
      stage, the O2 concentration in the infected zone increased to 1%, which may be
      sufficient to inactivate N2ase; however, key enzymes of carbon and nitrogen
      metabolism were still active. After 2 d of dark stress there was a significant
      decrease in the level of N2ase proteins and in the activities of enzymes involved
      in carbon and nitrogen assimilation. However, the general collapse of nodule
      metabolism occurred only after 4 d of stress, with a large decline in
      leghemoglobin and antioxidants. At this final senescent stage, there was an
      accumulation of oxidatively modified proteins. This oxidative stress may have
      originated from the decrease in antioxidant defenses and from the Fe-catalyzed
      generation of activated oxygen due to the increased availability of catalytic Fe
      and O2 in the infected region.

PMID- 12223670
TI  - Chemical Composition of Hypodermal and Endodermal Cell Walls and Xylem Vessels
      Isolated from Clivia miniata (Identification of the Biopolymers Lignin and
      Suberin).
AB  - The occurrence of the biopolymers lignin and suberin was investigated with
      hypodermal (HCW) and endodermal cell walls (ECW) and xylem vessels (XV) isolated
      from Clivia miniata Reg. roots. Both biopolymers were detected in HCW and ECW,
      whereas in XV, typical aliphatic suberin monomers were missing and only
      representative lignin monomers such as guaiacyl (G) and syringyl (S) units could
      be detected. The absolute amounts of lignin were about one order of magnitude
      higher compared with suberin in both HCW and ECW. The ratios of the two aromatic
      lignin units (G/S) decreased from 39 in XV and 10 in HCW to about 1 in ECW,
      indicating significant differences in lignin structure and function between the
      three investigated samples. Additionally, compared with the detectable lignin
      derived aromatic units G and S, significantly higher amounts of esterified p
      coumaric acid-derived aromatic monomers were obtained with HCW, but not with ECW.
      This is interpreted as a functional adaption of HCW toward pathogen defense at
      the root/soil interface. The final aim of this study was to provide a thorough
      chemical characterization of the composition of HCW, ECW, and XV, which in turn
      will form the basis for a better understanding of the relevant barriers toward
      the passive, radial, and apoplastic diffusion of solutes from the soil across the
      root cortex into the root cylinder.

PMID- 12223671
TI  - P Metabolism in the Bean-Rhizobium tropici Symbiosis.
AB  - Nodulated legumes require more P than legumes growing on mineral nitrogen, but
      little is known about the basis for the higher P requirement. Experiments were
      conducted to determine how Rhizobium tropici responds to P limitation and to
      understand how P is partitioned between the symbionts under conditions of
      adequate or limiting P. Free-living R. tropici responds to P stress by increasing
      P transport capacity and inducing both an acid and an alkaline phosphatase. This
      P-stress response occurs when the medium P concentration decreases below 1 [mu]M.
      Both P-stress-inducible phosphatases are found in bacteroids taken from plants
      growing with adequate P, suggesting that P levels in the symbiosome space is low
      enough to induce the expression of these enzymes. Bacteroid alkaline phosphatase
      specific activity was highest during vegetative growth of the bean plant, but
      decreased approximately 75% during the host reproductive stages. In hydroponic
      experiments 32P-tracer studies showed that in vivo rates of P accumulation were
      significantly higher in bacteroids from P-limited plants compared with those from
      plants that had been supplied with adequate P. In contrast, label accumulation in
      leaves was greatest in plants grown with adequate P.

PMID- 12223672
TI  - Relationship of Endo-[beta]-D-Mannanase Activity and Cell Wall Hydrolysis in
      Tomato Endosperm to Germination Rates.
AB  - The endosperm tissue enclosing the radicle tip (endosperm cap) governs radicle
      emergence in tomato (Lycopersicon esculentum Mill.) seeds. Weakening of the
      endosperm cap has been attributed to hydrolysis of its mannan-rich cell walls by
      endo-[beta]-D-mannanase. To test this hypothesis, we measured mannanase activity
      in tomato endosperm caps from seeds allowed to imbibe under conditions of varying
      germination rates. Over a range of suboptimal temperatures, mannanase activity
      prior to radicle emergence increased in accordance with accumulated thermal time.
      Reduced water potential delayed or prevented radicle emergence but enhanced
      mannanase activity in the endosperm caps. Abscisic acid did not prevent the
      initial increase in mannanase activity, although radicle emergence was markedly
      delayed. Sugar composition and percent mannose (Man) content of endosperm cap
      cell walls did not change prior to radicle emergence under any condition. Man,
      glucose, and other sugars were released into the incubation solution by endosperm
      caps isolated from intact seeds during imbibition. Pregerminative release of Man
      was suppressed and the release of glucose was enhanced when seeds were incubated
      in osmoticum or abscisic acid; the opposite occurred in the presence of
      gibberellin. Thus, whereas sugar release patterns were sensitive to environmental
      and hormonal factors affecting germination, neither assayable endo-[beta]-D
      mannanase activity nor changes in cell wall sugar composition of endosperm caps
      correlated well with tomato seed germination rates under all conditions.

PMID- 12223674
TI  - Discrimination Processes and Shifts in Carboxylation during the Phases of
      Crassulacean Acid Metabolism.
AB  - The magnitude and extent of Crassulacean acid metabolism (CAM) activity in two
      Clusia species was manipulated to investigate the regulation of the distinct CAM
      phases. First, in response to leaf-air vapor pressure deficit at night, changes
      in leaf conductance altered on-line carbon-isotope discrimination throughout the
      theoretical range for dark CO2 uptake during CAM. These ranged from the limit set
      by phosphoenolpyruvate carboxylase (PEPc) (-6[per mille (thousand) sign],
      [delta]13C equivalent of -2[per mille (thousand) sign]) to that imposed by
      diffusion limitation (+4[per mille (thousand) sign], [delta]13C equivalent of 
      12[per mille (thousand) sign]), but the lowest carbon-isotope discrimination
      occurred when P[square root]pa was only 0.7. Second, when the availability of
      external or internal sources of CO2 was reduced for both field- and greenhouse
      grown plants, CO2 uptake by day via PEPc during phase II largely compensated.
      Third, by reducing the dark period, plants accumulated low levels of acidity, and
      CO2 uptake occurred throughout the subsequent light period. Discrimination
      switched from being dominated by PEPc (phase II) to ribulose 1,5-bisphosphate
      carboxylase/oxygenase (phase III), with both enzymes active during phase IV.
      Under natural conditions, photochemical stability is maintained by extended PEPc
      activity in phase II, which enhances acid accumulation and delays decarboxylation
      until temperature and light stress are maximal at midday.

PMID- 12223673
TI  - RNase Activity Decreases following a Heat Shock in Wheat Leaves and Correlates
      with Its Posttranslational Modification.
AB  - Heat shock results in a coordinate loss of translational efficiency and an
      increase in mRNA stability in plants. The thermally mediated increase in mRNA
      half-life could be a result of decreased expression and/or regulation of
      intracellular RNase enzyme activity. We have examined the fate of both acidic and
      neutral RNases in wheat seedlings that were subjected to a thermal stress. We
      observed that the activity of all detectable RNases decreased following a heat
      shock, which was a function of both the temperature and length of the heat shock.
      In contrast, no reduction in nuclease activity was observed following any heat
      shock treatment. Antibodies raised against one of the major RNases was used in
      western analysis to demonstrate that the RNase protein level did not decrease
      following a heat shock, and the data suggest that the observed decrease in RNase
      activity in heat-shocked leaves may be due to modification of the protein. Two
      dimensional gel/western analysis of this RNase revealed three isoforms. The most
      acidic isoform predominated in control leaves, whereas the most basic isoform
      predominated in leaves following a heat shock and correlated with the heat-shock
      induced reduction in RNase activity and increase in mRNA half-life. These data
      suggest that RNase activity may be regulated posttranslationally following heat
      shock as a means to reduce RNA turnover until recovery ensues.

PMID- 12223675
TI  - On the Mechanism of Reinitiation of Endogenous Crassulacean Acid Metabolism
      Rhythm by Temperature Changes.
AB  - Under continuous light the endogenous Crassulacean acid metabolism (CAM) rhythm
      of Kalanchoe daigremontiana Hamet et Perrier de la Bathie disappears at high
      (>29.0[deg]C) or low (<8.0[deg]C) temperatures. We investigated the reinitiation
      of rhythmicity when temperature was reduced from above the upper and increased
      from below the lower threshold level via measurements of (a) short-term changes
      in carbon-isotope discrimination to illustrate shifts between C3 and C4
      carboxylation in vivo, and (b) the malate sensitivity of phosphoenolpyruvate
      carboxylase (PEPC) in vitro. When the net CO2-exchange rhythm disappears at both
      temperatures, the instantaneous discrimination indicates low PEPC activity. Leaf
      malate concentration and osmolarity attain high and low values at low and high
      temperatures, respectively. After small temperature increases or reductions from
      the low and high temperatures, respectively, the rhythm is reinitiated, with
      phases shifted by 180[deg] relative to each other. This can be related to the
      contrasting low and high leaf malate concentrations due to direct inhibition of
      PEPC and possibly also of the phosphorylation of PEPC by malate. The experimental
      results were satisfactorily simulated by a mathematical CAM-cycle model, with
      temperature acting only on the passive efflux of malate from the vacuole. We
      stress the important role of the tonoplast in malate compartmentation and of
      malate itself for the reinitiation and generation of endogenous CAM rhythmicity.

PMID- 12223676
TI  - Identification of a Soluble, High-Affinity Salicylic Acid-Binding Protein in
      Tobacco.
AB  - Salicylic acid (SA) is a key component in the signal transduction pathway(s),
      leading to the activation of certain defense responses in plants after pathogen
      attack. Previous studies have identified several proteins, including catalase and
      ascorbate peroxidase, through which the SA signal might act. Here we describe a
      new SA-binding protein. This soluble protein is present in low abundance in
      tobacco (Nicotiana tabacum) leaves and has an apparent molecular weight of
      approximately 25,000. It reversibly binds SA with an apparent dissociation
      constant of 90 nM, an affinity that is 150-fold higher than that between SA and
      catalase. The ability of most analogs of SA to compete with labeled SA for
      binding to this protein correlated with their ability to induce defense gene
      expression and enhanced resistance. Strikingly, benzothiadiazole, a recently
      described chemical activator that induces plant defenses and disease resistance
      at very low rates of application, was the strongest competitor, being much more
      effective than unlabeled SA. The possible role of this SA-binding protein in
      defense signal transduction is discussed.

PMID- 12223677
TI  - In Vivo Studies of the Biosynthesis of [alpha]-Eleostearic Acid in the Seed of
      Momordica charantia L.
AB  - In vivo radiotracer experiments using 14C-labeled acetate, oleate, linoleate, and
      linolenate were conducted to investigate the biosynthesis of [alpha]-eleostearic
      acid in the seeds of Momordica charantia. With the exception of [14C]linolenate,
      all of these precursors radioactively labeled [alpha]-eleostearate. Kinetics of
      the time course of metabolism of the radioactive precursors indicate that
      linoleate is the acyl precursor of [alpha]-eleostearate and that its conversion
      to [alpha]-eleostearate occurs while the acyl moiety is esterified to PC. Pulse
      chase experiments with 14C-labeled acetate or linoleate provided additional
      corroborative evidence that linoleoyl PC is the precursor of [alpha]-eleostearoyl
      PC.

PMID- 12223678
TI  - Direct Evaluation of the Ca2+-Displacement Hypothesis for Al Toxicity.
AB  - One explanation for Al toxicity in plants suggests that Al displaces Ca2+ from
      critical sites in the apoplasm. We evaluated the Ca2+-displacement hypothesis
      directly using near-isogenic lines of wheat (Triticum aestivum L.) that differ in
      Al tolerance at a single locus. We measured both the growth and total
      accumulation (apoplasmic plus symplasmic) of 45Ca and Al into roots that had been
      exposed to Al alone or to Al with other cations. Root growth in the Al-sensitive
      line was found to be severely inhibited by low activities of Al, even though Ca2+
      accumulation was relatively unaffected. In solutions containing the same activity
      of the Al3+ and Ca2+ ions as above, but also including either 3.0 mM Mg2+, 3.0 mM
      Sr2+, or 30 mM Na+, growth improved, whereas 45Ca2+ accumulation was
      significantly decreased. Since most of the 45Ca2+ accumulated by roots during
      short-term treatments will reside in the apoplasm, these results indicate that
      displacement of Ca2+ from the apoplasm by Al cannot account for the Al-induced
      inhibition of root growth and, therefore, do not support the Ca2+-displacement
      hypothesis for Al toxicity. We also show that total accumulation of Al by root
      apices is greater in the Al-sensitive genotype than the Al-tolerant genotype and
      suggest that cation amelioration of Al toxicity is caused by the reduction in Al
      accumulation.

PMID- 12223679
TI  - Novel Phosphoinositides in Barley Aleurone Cells (Additional Evidence for the
      Presence of Phosphatidyl-scyllo-Inositol).
AB  - A novel isomer of phosphatidylinositol that differs in the structure of the head
      group was detected in barley (Hordeum vulgare cv Himalaya) seeds. In this paper
      we describe our efforts to elucidate the structure of the novel isomer. Evidence
      from a variety of techniques, including chemical modification of in vivo 32Pi-
      and myo-[3H]inositol-labeled compounds, gas chromatography-mass spectrometry
      analysis, in vivo incorporation of scyllo-[3H]inositol, and enzymatic studies
      that suggest that the structure is phosphatidylscyllo-inositol (scyllo-PI), is
      presented. The use of microwave energy to significantly enhance the slow rate of
      hydrolysis of phosphoinositides is described. The presence of scyllo-PI can be
      easily overlooked by the methods commonly employed; therefore, experimental
      considerations important for the detection of scyllo-PI are discussed.

PMID- 12223680
TI  - The Determination of Relative Elemental Growth Rate Profiles from Segmental
      Growth Rates (A Methodological Evaluation).
AB  - Relative elemental growth rate (REGR) profiles describe spatial patterns of
      growth intensity; they are indispensable for causal growth analyses. Published
      methods of REGR profile determination from marking experiments fall in two
      classes: the profile is either described by a series of segmental growth rates,
      or calculated as the slope of a function describing the displacement velocities
      of points along the organ. The latter technique is usually considered superior
      for theoretical reasons, but to our knowledge, no comparative methodological
      study of the two approaches is currently available. We formulated a model REGR
      profile that resembles those reported from primary roots. We established the
      displacement velocity profile and derived growth trajectories, which enabled us
      to perform hypothetical marking experiments on the model with varying spacing of
      marks and durations of measurement. REGR profiles were determined from these data
      by alternative methods, and results were compared to the original profile. We
      find that with our model plotting of segmental relative growth rates versus
      segment position provides exact REGR profile estimations, if the initial segment
      length is less than 10% of the length of the whole growing zone, and if less than
      20% of the growing zone is displaced past its boundary during the measurement.
      Based on our analysis, we discuss systematic errors that occur in marking
      experiments.

PMID- 12223681
TI  - Localization of Pectic Galactan in Tomato Cell Walls Using a Monoclonal Antibody
      Specific to (1[->]4)-[beta]-D-Galactan.
AB  - To develop antibody probes for the neutral side chains of pectins, antisera were
      generated to a pectic galactan isolated from tomato (Lycopersicon esculentum)
      pericarp cell walls and to a (1[->]4)-[beta]-galactotetraose-bovine serum albumin
      neoglycoprotein. The use of these two antisera in immunochemical assays and
      immunolocalization studies indicated that they had very similar specificities. A
      monoclonal antibody (LM5) was isolated and characterized subsequent to
      immunization with the neoglycoprotein. Hapten inhibition studies revealed that
      the antibody specifically recognized more than three contiguous units of (1[->]4)
      [beta]-galactosyl residues. The antigalactan antibody was used to immunolocalize
      the galactan side chains of pectin in tomato fruit pericarp and tomato petiole
      cell walls. Although the LM5 epitope occurs in most cell walls of the tomato
      fruit, it was absent from both the locular gel and the epidermal and subepidermal
      cells. Furthermore, in contrast to other anti-pectin antibodies, LM5 did not
      label the cell wall thickenings of tomato petiole collenchyma.

PMID- 12223682
TI  - [delta]1-Pyrroline-5-Carboxylate Dehydrogenase from Cultured Cells of Potato
      (Purification and Properties).
AB  - [delta]1-Pyrroline-5-carboxylate (P5C) dehydrogenase (EC 1.5.1.12), the second
      enzyme in the proline catabolic pathway and a catalyst for the oxidation of P5C
      to glutamate, was purified from cultured potato (Solanum tuberosum L. var
      Desiree) cells. Homogeneous enzyme preparations were obtained by a three-step
      procedure that used anion-exchange, adsorption, and substrate elution
      chromatography. A 1600-fold purification was achieved, with a recovery of one
      third of the initial activity. The purified enzyme was characterized with respect
      to structural, kinetic, and biochemical properties. It appeared to be an [alpha]
      4 tetramer with subunits of an apparent molecular mass of about 60 kD and had a
      mildly acidic isoelectric point value. Potato P5C dehydrogenase had Michaelis
      constant values of 0.11 and 0.46 mM for NAD+ and P5C, respectively. Although NAD+
      was the preferred electron acceptor, NADP+ also yielded an unusually high rate,
      and thus was found to serve as a substrate. Maximal activity was observed at pH
      values in the 7.3 to 8.3 range, and was progressively inhibited by chloride ions,
      a finding that strengthens recent suggestions that hyperosmotic stress negatively
      modulates in vivo proline oxidation.

PMID- 12223683
TI  - Characterization of a Light-Controlled Anion Channel in the Plasma Membrane of
      Mesophyll Cells of Pea.
AB  - In leaf mesophyll cells of pea (Pisum sativum) light induces a transient
      depolarization that is at least partly due to an increased plasma membrane
      conductance for anions. Several channel types were identified in the plasma
      membrane of protoplasts from mesophyll cells using the patch-clamp technique. One
      of these was an anion channel with a single-channel conductance of 32 picasiemens
      in symmetrical 100/100 KCl solutions. In asymmetrical solutions the reversal
      potential indicates a high selectivity for Cl- over K+ at high cytoplasmic Cl-.
      At negative membrane voltages the channel openings were interrupted by very short
      closures. In the open channel conductance several substrates were identified. At
      a cytoplasmic negative logarithm of Ca concentration higher than 6.3, no channel
      openings were observed. When the protoplast was illuminated in the cell-attached
      configuration, at least one channel type had a higher opening probability. This
      channel can tentatively be identified as the above-described anion channel based
      on conductance and the characteristic short closures at negative membrane
      potentials. This light activation of the 32-picasiemen anion channel is a strong
      indication that this channel conducts the light-induced depolarizing current.
      Because channel activity is strongly Ca2+-dependent, a role of cytoplasmic Ca2+
      concentration changes in the light activation of the conductance is discussed.

PMID- 12223684
TI  - Transgenically Expressed Betaine Aldehyde Dehydrogenase Efficiently Catalyzes
      Oxidation of Dimethylsulfoniopropionaldehyde and [omega]-Aminoaldehydes.
AB  - Tobacco (Nicotianum tabacum L.) plants engineered to express a sugar beet (Beta
      vulgaris L.) betaine aldehyde dehydrogenase (BADH) cDNA acquired not only BADH
      activity, but also three other aldehyde dehydrogenase activities (those measured
      with 3-dimethylsulfoniopropionaldehyde, 3-aminopropionaldehyde, and 4
      aminobutyraldehyde, all of which are natural products). This shows that BADH is
      not, as believed up to now, a substrate-specific enzyme and that its role may not
      be limited to glycine betaine synthesis.

PMID- 12223685
TI  - Bioprotective Alkaloids of Grass-Fungal Endophyte Symbioses.

PMID- 12223686
TI  - Tissue-Specific and Development-Dependent Accumulation of Phenylpropanoids in
      Larch Mycorrhizas.
AB  - The tissue-specific and development-dependent accumulation of secondary products
      in roots and mycorrhizas of larch (Larix decidua Mill.; Pinaceae) was studied
      using high-performance liquid chromatography and histochemical methods. The
      compounds identified were soluble catechin, epicatechin, quercetin 3-O-[alpha]
      rhamnoside, cyanidin- and peonidin 3-O-[beta]-glucoside, 4-O-[beta]
      hydroxybenzoyl-O-[beta]-glucose, 4-hydroxybenzoate 4-O-[beta]-glucoside, maltol 3
      O-[beta]-glucoside, and the wall-bound 4-hydroxybenzaldehyde, vanillin, and
      ferulate. In addition, we partially identified a tetrahydroxystilbene
      monoglycoside, a quercetin glycoside, and eight oligomeric proanthocyanidins.
      Comparison between the compounds accumulating in the apical tissue of fine roots,
      long roots, and in vitro grown mycorrhizas (L. decidua-Suillus tridentinus)
      showed elevated levels of the major compounds catechin and epicatechin as well as
      the minor compound 4-hydroxybenzoate 4-O-[beta]-glucoside specifically in the
      root apex of young mycorrhizas. The amounts of wall-bound 4-hydroxybenzaldehyde
      and vanillin were increased in all of the mycorrhizal sections examined. During
      the early stages of mycorrhization the concentrations of these compounds
      increased rapidly, perhaps induced by the mycorrhizal fungus. In addition,
      studies of L. decidua-Boletinus cavipes mycorrhizas from a natural stand showed
      that the central part of the subapical cortex tissue and the endodermis both
      accumulate massive concentrations of catechin, epicatechin, and wall-bound
      ferulate compared with the outer part of the cortex, where the Hartig net is
      being formed.

PMID- 12223687
TI  - The Cytosolic Ca2+ Concentration Gradient of Sinapis alba Root Hairs as Revealed
      by Ca2+-Selective Microelectrode Tests and Fura-Dextran Ratio Imaging.
AB  - Using Ca2+-selective microelectrodes and fura 2-dextran ratio imaging, the
      cytosolic free [Ca2+] was measured in Sinapis alba root hair cells. Both methods
      yielded comparable results, i.e. values between 158 to 251 nM for the basal
      [Ca2+] of the cells and an elevated [Ca2+] of 446 to 707 nM in the tip region.
      The zone of elevated [Ca2+] reaches 40 to 60 [mu]m into the cell and is congruent
      with the region of inwardly directed Ca2+ net currents measured with an external
      Ca2+- selective vibrating electrode. The channel-blocker La3+ eliminates these
      currents, stops growth, and almost completely eliminates the cytosolic [Ca2+]
      gradient without affecting the basal level of the ion. Growth is also inhibited
      by pressure-injected dibromo-1,2-bis(o-aminophenoxy)ethane-N,N,N[prime],N[prime]
      tetraacetic acid, which causes a decrease in the [Ca2+] in the tip in a
      concentration-dependent manner. Indole-3-acetic acid, used as a model stimulus,
      decreases cytosolic free [Ca2+] by 0.2 to 0.3 pCa units in the tip, but only by
      about 0.1 pCa unit in the shank. Nongrowing root hairs may or may not display a
      [Ca2+] gradient, but still reversibly respond to external stimuli such as La3+,
      Ca2+, or indole-3-acetic acid with changes in cytosolic free [Ca2+]. During short
      time periods, dicyclohexylcarbodiimide inhibition of the plasma membrane H+
      ATPase, which stops growth, does not abolish the [Ca2+] gradient, nor does it
      change significantly the basal [Ca2+] level. We conclude that the cytosolic
      [Ca2+] gradient and an elevated [Ca2+] in the tip, as in other tip-growing cells,
      is essential for tip growth in root hairs; however, its presence does not
      indicate growth under all circumstances. We argue that with respect to Ca2+, tip
      growth regulation and responses to external signals may not interfere with each
      other. Finally, we suggest that the combination of the methods applied adds
      considerably to our understanding of the role of cytosolic free [Ca2+] in signal
      transduction and cellular growth.

PMID- 12223688
TI  - The Spatial Distribution of Sucrose Synthase Isozymes in Barley.
AB  - The sucrose (Suc) synthase enzyme purified from barley (Hordeum vulgare L.) roots
      is a homotetramer that is composed of 90-kD type 1 Suc synthase (SS1) subunits.
      Km values for Suc and UDP were 30 mM and 5 [mu]M, respectively. This enzyme can
      also utilize ADP at 25% of the UDP rate. Anti-SS1 polyclonal antibodies, which
      recognized both SS1 and type 2 Suc synthase (SS2) (88-kD) subunits, and
      antibodies raised against a synthetic peptide, LANGSTDNNFV, which were specific
      for SS2, were used to study the spatial distribution of these subunits by
      immunoblot analysis and immunolocalization. Both SS1 and SS2 were abundantly
      expressed in endosperm, where they polymerize to form the five possible homo- and
      heterotetramers. Only SS1 homotetramers were detected in young leaves, where they
      appeared exclusively in phloem cells, and in roots, where expression was
      associated with cap cells and the vascular bundle. In the seed both SS1 and SS2
      were present in endosperm, but only SS1 was apparent in the chalazal region, the
      nucellar projection, and the vascular bundle. The physiological implications for
      the difference in expression patterns observed are discussed with respect to the
      maize (Zea mays L.) model.

PMID- 12223689
TI  - Metabolism of Hydroxy Fatty Acids in Developing Seeds in the Genera Lesquerella
      (Brassicaceae) and Linum (Linaceae).
AB  - Members of the genus Lesquerella produce seed oil that contains a high proportion
      of hydroxy fatty acids (HFAs). There are three groups of Lesquerella species that
      are distinguished by their most abundant seed oil fatty acid: lesquerolic acid
      (20:1OH; e.g. Lesquerella fendleri), densipolic acid (18:2OH; e.g. Lesquerella
      kathryn), and auricolic acid (20:2OH; e.g. Lesquerella auriculata). To
      investigate the biochemistry of HFA production in Lesquerella species, the
      conversion of putative radiolabeled intermediates of HFA biosynthesis, including
      18:1, 20:1,18:1OH, 18:2OH, and 20:1OH, was examined in developing embryos of L.
      fendleri, L.kathryn, and L. auriculata. The results are consistent with (a)
      18:1OH formation by hydroxylation of 18:1, (b) elongation and desaturation of
      18:1OH to produce 20:1OH and 18:2OH, respectively, and (c) desaturation of 20:1OH
      to produce 20:2OH. The desaturation of 20:1OH was also found to occur in
      developing embryos of high, but not low, linolenic acid flax. This suggests that
      the desaturation is catalyzed by the extraplastidial linoleate desaturase.
      Confirming this suggestion, it was notable that 18:1OH and 18:2OH were found in
      low and high linolenic flax (Linum usitatissimum) seeds, respectively, at levels
      of 0.2 to 1%.

PMID- 12223690
TI  - Jasmonate-Inducible Genes Are Activated in Rice by Pathogen Attack without a
      Concomitant Increase in Endogenous Jasmonic Acid Levels.
AB  - The possible role of the octadecanoid signaling pathway with jasmonic acid (JA)
      as the central component in defense-gene regulation of pathogen-attacked rice was
      studied. Rice (Oryza sativa L.) seedlings were treated with JA or inoculated with
      the rice blast fungus Magnaporthe grisea (Hebert) Barr., and gene-expression
      patterns were compared between the two treatments. JA application induced the
      accumulation of a number of pathogenesis-related (PR) gene products at the mRNA
      and protein levels, but pathogen attack did not enhance the levels of (-)-JA
      during the time required for PR gene expression. Pathogen-induced accumulation of
      PR1-like proteins was reduced in plants treated with tetcyclacis, a novel
      inhibitor of jasmonate biosynthesis. There was an additive and negative
      interaction between JA and an elicitor from M. grisea with respect to induction
      of PR1-like proteins and of an abundant JA-and wound-induced protein of 26 kD,
      respectively. Finally, activation of the octadecanoid signaling pathway and
      induction of a number of PR genes by exogenous application of JA did not confer
      local acquired resistance to rice. The data suggest that accumulation of
      nonconjugated (-)-JA is not necessary for induction of PR genes and that JA does
      not orchestrate localized defense responses in pathogen-attacked rice. Instead,
      JA appears to be embedded in a signaling network with another pathogen-induced
      pathway(s) and may be required at a certain minimal level for induction of some
      PR genes.

PMID- 12223691
TI  - 8[prime]-Methylene Abscisic Acid (An Effective and Persistent Analog of Abscisic
      Acid).
AB  - We report here the synthesis and biological activity of a new persistent abscisic
      acid (ABA) analog, 8[prime]-methylene ABA. This ABA analog has one additional
      carbon atom attached through a double bond to the 8[prime]-carbon of the ABA
      molecule. (+)-8[prime]-Methylene ABA is more active than the natural hormone (+)
      ABA in inhibiting germination of cress seed and excised wheat embryos, in
      reducing growth of suspension-cultured corn cells, and in reducing transpiration
      in wheat seedlings. The (+)-8[prime]-methylene analog is slightly weaker than (+)
      ABA in increasing expression of ABA-inducible genes in transgenic tobacco, but is
      equally active in stimulating a transient elevation of the pH of the medium of
      corn cell cultures. In corn cells, both (+)-ABA and (+)-8[prime]-methylene ABA
      are oxidized at the 8[prime] position. ABA is oxidized to phaseic acid and (+)
      8[prime]-methylene ABA is converted more slowly to two isomeric epoxides. The
      alteration in the ABA structure causes the analog to be metabolized more slowly
      than ABA, resulting in longer-lasting and more effective biological activity
      relative to ABA.

PMID- 12223692
TI  - Topography and Function of Golgi Uridine-5[prime]-Diphosphatase from Pea Stems.
AB  - Golgi UDPase is an enzyme that has been shown to function in polysaccharide
      biosynthesis, but its role in this process is not yet clear. In this study we
      identified Golgi UDPase activity in pea (Pisum sativum) stems and differentiated
      it from another UDPase activity. We demonstrated that Golgi UDPase is an integral
      membrane protein, based on specific partitioning of this activity into Triton X
      114. Analysis of its topology using sealed, right-side-out Golgi vesicles and
      treatment with proteinase K suggested that its active site faces the Golgi lumen.
      Studies aimed at understanding the function of Golgi UDPase by incubating Golgi
      vesicles with [beta]-32P]UDP-glucose (Glc) to generate [beta]-32P]UDP upon Glc
      transfer in situ showed that 32Pi, but not [beta]-32P]UDP, was formed, suggesting
      that UDPase quickly hydrolyzed the UDP formed during Glc polymerization. We found
      that the Golgi UDPase was highly active in the elongating region of the third
      internode, whereas no activity was detected in the first and second internodes of
      etiolated pea seedlings. These results suggest that UDPase removes the UDP formed
      during Glc polymerization and could be important in the mechanism of
      polysaccharide biosynthesis.

PMID- 12223693
TI  - A New Mechanism for the Regulation of Stomatal Aperture Size in Intact Leaves
      (Accumulation of Mesophyll-Derived Sucrose in the Guard-Cell Wall of Vicia faba).
AB  - At various times after pulse-labeling broad bean (Vicia faba L.) leaflets with
      14CO2, whole-leaf pieces and rinsed epidermal peels were harvested and
      subsequently processed for histochemical analysis. Cells dissected from whole
      leaf retained apoplastic contents, whereas those from rinsed peels contained only
      symplastic contents. Sucrose (Suc)-specific radioactivity peaked (111 GBq mol-1)
      in palisade cells at 20 min. In contrast, the 14C content and Sucspecific
      radioactivity were very low in guard cells for 20 min, implying little CO2
      incorporation; both then peaked at 40 min. The guard-cell apoplast had a high
      maximum Suc-specific radioactivity (204 GBq mol-1) and a high Suc influx rate
      (0.05 pmol stoma-1 min-1). These and other comparisons implied the presence of
      (a) multiple Suc pools in mesophyll cells, (b) a localized mesophyll-apoplast
      region that exchanges with phloem and stomata, and (c) mesophyll-derived Suc in
      guard-cell walls sufficient to diminish stomatal opening by approximately 3
      [mu]m. Factors expected to enhance Suc accumulation in guard-cell walls are (a)
      high transpiration rate, which closes stomata, and (b) high apoplastic Suc
      concentration, which is elevated when mesophyll Suc efflux exceeds translocation.
      Therefore, multiple physiological factors are integrated in the attenuation of
      stomatal aperture size by this previously unrecognized mechanism.

PMID- 12223694
TI  - Modification of Photosystem I Light Harvesting of Bundle-Sheath Chloroplasts
      Occurred during the Evolution of NADP-Malic Enzyme C4 Photosynthesis.
AB  - Low-temperature emission spectra and excitation spectra for chlorophyll
      fluorescence were recorded from leaves of species of the genus Flaveria
      (Asteraceae) with C3, C3-C4-intermediate, C4-like, and C4 photosynthesis. Among
      the latter two groups, high chlorophyll b absorption was observed in excitation
      spectra for photosystem I (PSI) fluorescence. By comparing leaf data with those
      from isolated chloroplast fractions, the high chlorophyll b absorption was
      attributed to the specific properties of the bundle-sheath chloroplasts in leaves
      from C4 plants. The deconvolution of the PSI excitation spectra and the use of a
      model revealed that the contribution of photosystem II absorption to the
      functional antenna of PSI was markedly increased in leaves from three of the five
      C4-like and C4 species investigated in detail. The two other species exhibited
      normal, C3-like light-harvesting properties of PSI. The former species are known
      for efficient carbon assimilation, the latter for decreased efficiencies of
      carbon assimilation. It is concluded that photosystem II becomes a substantial
      part of the functional PSI antenna late in the evolution of C4 photosynthesis,
      and that the composite antenna optimizes the light-harvesting of PSI in bundle
      sheath chloroplasts to meet the energy requirements of C4 photosynthesis.

PMID- 12223695
TI  - Carbohydrate Content and Enzyme Metabolism in Developing Canola Siliques.
AB  - Little biochemical information is available on carbohydrate metabolism in
      developing canola (Brassica napus L.) silique (pod) wall and seed tissues. This
      research examines the carbohydrate contents and sucrose (Suc) metabolic enzyme
      activities in different aged silique wall and seed tissues during oil filling.
      The silique wall partitioned photosynthate into Suc over starch and predominantly
      accumulated hexose. The silique wall hexose content and soluble acid invertase
      activity rapidly fell as embryos progressed from the early- to late-cotyledon
      developmental stages. A similar trend was not evident for alkaline invertase, Suc
      synthase (SuSy), and Suc-phosphate synthase. Silique wall SuSy activities were
      much higher than source leaves at all times and may serve to supply the substrate
      for secondary cell wall thickening. In young seeds starch was the predominant
      accumulated carbohydrate over the sampled developmental range. Seed hexose levels
      dropped as embryos developed from the early- to midcotyledon stage. Hexose and
      starch were localized to the testa or liquid endosperm, whereas Suc was evenly
      distributed among seed components. With the switch to oil accumulation, seed SuSy
      activity increased by 3.6-fold and soluble acid invertase activity decreased by
      76%. These data provide valuable baseline knowledge for the genetic manipulation
      of canola seed carbon partitioning.

PMID- 12223696
TI  - The Role of Sugars, Hexokinase, and Sucrose Synthase in the Determination of
      Hypoxically Induced Tolerance to Anoxia in Tomato Roots.
AB  - Hypoxic pretreatment of tomato (Lycopersicon esculentum M.) roots induced an
      acclimation to anoxia. Survival in the absence of oxygen was improved from 10 h
      to more than 36 h if external sucrose was present. The energy charge value of
      anoxic tissues increased during the course of hypoxic acclimation, indicating an
      improvement of energy metabolism. In acclimated roots ethanol was produced
      immediately after transfer to anoxia and little lactic acid accumulated in the
      tissues. In nonacclimated roots significant ethanol synthesis occurred after a 1
      h lag period, during which time large amounts of lactic acid accumulated in the
      tissues. Several enzyme activities, including that of alcohol dehydrogenase,
      lactate dehydrogenase, pyruvate decarboxylase, and sucrose synthase, increased
      during the hypoxic pretreatment. In contrast to maize, hexokinase activities did
      not increase and phosphorylation of hexoses was strongly inhibited during anoxia
      in both kinds of tomato roots. Sucrose, but not glucose or fructose, was able to
      sustain glycolytic flux via the sucrose synthase pathway and allowed anoxic
      tolerance of acclimated roots. These results are discussed in relation to
      cytosolic acidosis and the ability of tomato roots to survive anoxia.

PMID- 12223697
TI  - Glutathione-Mediated Regulation of ATP Sulfurylase Activity, SO42- Uptake, and
      Oxidative Stress Response in Intact Canola Roots.
AB  - The dual role of glutathione as a transducer of S status (A.G. Lappartient and B.
      Touraine [1996] Plant Physiol 111: 147-157) and as an antioxidant was examined by
      comparing the effects of S deprivation, glutathione feeding, and H2O2 (oxidative
      stress) on SO42- uptake and ATP sulfurylase activity in roots of intact canola
      (Brassica napus L.). ATP sulfurylase activity increased and SO42- uptake rate
      severely decreased in roots exposed to 10 mM H2O2, whereas both increased in S
      starved plants. In split-root experiments, an oxidative stress response was
      induced in roots remote from H2O2 exposure, as revealed by changes in the reduced
      glutathione (GSH) level and the GSH/oxidized glutathione (GSSG) ratio, but there
      was only a small decrease in SO42- uptake rate and no effect on ATP sulfurylase
      activity. Feeding plants with GSH increased GSH, but did not affect the GSH/GSSG
      ratio, and both ATP sulfurylase activity and SO42- uptake were inhibited. The
      responses of the H2O2-scavenging enzymes ascorbate peroxidase and glutathione
      reductase to S starvation, GSH treatment, and H2O2 treatment were not to
      glutathione-mediated S demand regulatory process. We conclude that the regulation
      of ATP sulfurylase activity and SO42- uptake by S demand is related to GSH rather
      than to the GSH/GSSG ratio, and is distinct from the oxidative stress response.

PMID- 12223698
TI  - CO2 and Water Vapor Exchange across Leaf Cuticle (Epidermis) at Various Water
      Potentials.
AB  - Cuticular properties affect the gas exchange of leaves, but little is known about
      how much CO2 and water vapor cross the cuticular barrier or whether low water
      potentials affect the process. Therefore, we measured the cuticular conductances
      for CO2 and water vapor in grape (Vitis vinifera L.) leaves having various water
      potentials. The lower leaf surface was sealed to force all gas exchange through
      the upper surface, which was stoma-free. In this condition both gases passed
      through the cuticle, and the CO2 conductance could be directly determined from
      the internal mole fraction of CO2 near the compensation point, the external mole
      fraction of CO2, and the CO2 flux. The cuticle allowed small amounts of CO2 and
      water vapor to pass through, indicating that gas exchange occurs in grape leaves
      no matter how tightly the stomata are closed. However, the CO2 conductance was
      only 5.7% of that for water vapor. This discrimination against CO2 markedly
      affected calculations of the mole fraction of CO2 in leaves as stomatal apertures
      decreased. When the leaf dehydrated, the cuticular conductance to water vapor
      decreased, and transpiration and assimilation diminished. This dehydration effect
      was largest when turgor decreased, which suggests that cuticular gas exchange may
      have been influenced by epidermal stretching.

PMID- 12223699
TI  - Differential Accumulation of Salicylic Acid and Salicylic Acid-Sensitive Catalase
      in Different Rice Tissues.
AB  - We previously proposed that salicylic acid (SA)-sensitive catalases serve as
      biological targets of SA in plant defense responses. To further examine the role
      of SA-sensitive catalases, we have analyzed the relationship between SA levels
      and SA sensitivity of catalases in different rice (Oryza sativa) tissues. We show
      here that, whereas rice shoots contain extremely high levels of free SA, as
      previously reported (I. Raskin, H. Skubatz, W. Tang, B.J.D. Meeuse [1990] Ann Bot
      66: 369-373; P. Silverman, M. Seskar, D. Kanter, P. Schweizer, J.-P. Metraux, I.
      Raskin [1995] Plant Physiol 108: 633-639), rice roots and cell-suspension
      cultures have very low SA levels. Catalases from different rice tissues also
      exhibit differences in sensitivity to SA. Catalase from rice shoots is
      insensitive to SA, but roots and cell-suspension cultures contain SA-sensitive
      catalase. The difference in SA sensitivity of catalases from these different
      tissues correlates with the tissue-specific expression of two catalase genes,
      CatA and CatB, which encode highly distinctive catalase proteins. CatA, which
      encodes a catalase with relatively low sequence homology to the tobacco SA
      sensitive catalases, is expressed at high levels exclusively in the shoots. On
      the other hand, in roots and cell-suspension cultures, with northern analysis we
      detected expression of only the CatB gene, which encodes a catalase with higher
      sequence homology to tobacco catalases. The role of catalases in mediating some
      of the SA-induced responses is discussed in light of these results and the
      recently defined mechanisms of catalase inhibition by SA.

PMID- 12223700
TI  - Grain Development Mutants of Barley ([alpha]-Amylase Production during Grain
      Maturation and Its Relation to Endogenous Gibberellic Acid Content).
AB  - Barley (Hordeum vulgare L. Himalaya) mutants with altered grain morphology were
      isolated to investigate whether defects in grain development, possibly involving
      gibberellins (GAs) and abscisic acid, would lead to altered patterns of [alpha]
      amylase gene expression. Following treatment with sodium azide, 75 mutants,
      typically showing grain shriveling, were identified. At grain maturity 15 of the
      75 mutants had higher [alpha]-amylase activities in shriveled grains compared
      with either phenotypically normal grains that developed on the same heterozygous
      plant or with grains of cv Himalaya. Studies of four of these mutants
      demonstrated increased levels of both high- and low-isoelectric point [alpha]
      amylase isozymes midway through grain development. This category of mutant has
      been designated pga, for premature grain [alpha]-amylase. One such mutant (M326)
      showed an endosperm-determined inheritance pattern. When crossed into a (GA
      deficient) dwarfing background there was a 10- to 20-fold reduction in [alpha]
      amylase activity, suggesting a requirement for GA biosynthesis. Endogenous GAs
      and abscisic acid were quantified by combined gas chromatography-specific ion
      monitoring in normal and mutant grains of heterozygous M326 plants during the
      period of [alpha]-amylase accumulation. Mutant grains had significantly higher
      (5.8-fold) levels of the bioactive GA1 compared with normal grains but much lower
      (approximately 10-fold) levels of the 2[beta]-hydroxylated ("inactive") GAs,
      typical of developing barley grains (e.g. GA8, GA34, GA48). We propose that a
      reduced extent of 2[beta]-hydroxylation in the mutant grains results in an
      increased level of GA1, which is responsible for premature [alpha]-amylase gene
      expression.

PMID- 12223701
TI  - Elucidation of the Biosynthesis of Eicosapentaenoic Acid in the Microalga
      Porphyridium cruentum (II. Studies with Radiolabeled Precursors).
AB  - In the course of the study of the biosynthesis of the fatty acid eicosapentaenoic
      acid (EPA) in the microalga Porphyridium cruentum, cells were pulse-labeled with
      various radiolabeled fatty acid precursors. Our data show that the major end
      products of the biosynthesis are EPA-containing galactolipids of a eukaryotic and
      prokaryotic nature. The prokaryotic molecular species contain EPA and arachidonic
      acid at the sn-1 position and C16 fatty acids, mainly 16:0, at the sn-2
      positions, whereas in the eukaryotic species both positions are occupied by EPA
      or arachidonic acid. However, we suggest that both the eukaryotic and prokaryotic
      molecular species are formed in two pathways, [omega]6 and [omega]3, which
      involve cytoplasmic and chloroplastic lipids. In the [omega]6 pathway,
      cytoplasmic 18:2-phosphatidylcholine (PC) is converted to 20:4[omega]6-PC by a
      sequence that includes a [delta]6 desaturase, an elongation step, and a [delta]5
      desaturase. In the minor [omega]3 pathway, 18:2-PC is presumably desaturated to
      18:3[omega]3, which is sequentially converted by the enzymatic sequence of the
      [omega]6 pathway to 20:5[omega]3-PC. The products of both pathways are exported,
      as their diacylglycerol moieties, to the chloroplast to be galactosylated into
      their respective monogalactosyldiacylglycerol molecular species. The 20:4[omega]6
      in both eukaryotic and prokaryotic monogalactosyldiacylglycerol can be further
      desaturated to EPA by a chloroplastic [delta]17 ([omega]3) desaturase.

PMID- 12223702
TI  - Characterization and Purification of an Aldose Reductase from the Acidophilic and
      Thermophilic Red Alga Galdieria sulphuraria.
AB  - The acidophilic and thermophilic red alga Galdieria sulphuraria is able to grow
      heterotrophically on at least six different pentoses. These pentoses are reduced
      in the cell to pentiols by an NADP-dependent aldose reductase. The pentiols are
      then introduced into the oxidative pentose phosphate pathway via NAD-dependent
      polyol dehydrogenases and pentulokinases. The aldose reductase was purified 130
      fold to apparent homogeneity by column chromatography. The enzyme is a homodimer
      of about 80 kD, as estimated by size-exclusion chromatography and from the
      sedimentation behavior. The Michaelis constant values for D-xylose (27 mM), D
      ribose (29 mM), D-lyxose (30 mM), and D-arabinose (38 mM) were about three to
      five times lower than for the L-forms of the sugars. The activity of the enzyme
      with hexoses, deoxysugars, and sugar phosphates was only about 5 to 10% of the
      rate with pentoses. In the reverse reaction the activity was low and only
      detectable with pentiols. No activity was measured with NAD(H) as the cosubstrate
      in either direction.

PMID- 12223703
TI  - Suppression of Ripening-Associated Gene Expression in Tomato Fruits Subjected to
      a High CO2 Concentration.
AB  - High concentrations of CO2 block or delay the ripening of fruits. In this study
      we investigated the effects of high CO2 on ripening and on the expression of
      stress- and ripening-inducible genes in cherry tomato (Lycopersicon esculentum
      Mill.) fruit. Mature-green tomato fruits were submitted to a high CO2
      concentration (20%) for 3 d and then transferred to air. These conditions
      effectively inhibited ripening-associated color changes and ethylene production,
      and reduced the protein content. No clear-cut effect was observed on the
      expression of two proteolysis-related genes, encoding polyubiquitin and ubiquitin
      conjugating enzyme E2, respectively. Exposure of fruit to high CO2 also resulted
      in the strong induction of two genes encoding stress-related proteins: a ripening
      regulated heat-shock protein and glutamate decarboxylase. Induction of these two
      genes indicated that high CO2 had a stress effect, most likely through cytosolic
      acidification. In addition, high CO2 blocked the accumulation of mRNAs for genes
      involved in the main ripening-related changes: ethylene synthesis (1
      aminocyclopropane-1-carboxylic acid synthase and 1-aminocyclopropane-1-carboxylic
      acid oxidase), color (phytoene synthase), firmness (polygalacturonase), and sugar
      accumulation (acid invertase). The expression of ripening-specific genes was
      affected by CO2 regardless of whether their induction was ethylene- or
      development-dependent. It is proposed that the inhibition of tomato fruit
      ripening by high CO2 is due, in part, to the suppression of the expression of
      ripening-associated genes, which is probably related to the stress effect exerted
      by high CO2.

PMID- 12223704
TI  - Evidence for the Presence of the Ascorbate-Glutathione Cycle in Mitochondria and
      Peroxisomes of Pea Leaves.
AB  - The presence of the enzymes of the ascorbate-glutathione cycle was investigated
      in mitochondria and peroxisomes purified from pea (Pisum sativum L.) leaves. All
      four enzymes, ascorbate peroxidase (APX; EC 1.11.1.11), monodehydroascorbate
      reductase (EC 1.6.5.4), dehydroascorbate reductase (EC 1.8.5.1), and glutathione
      reductase (EC 1.6.4.2), were present in mitochondria and peroxisomes, as well as
      in the antioxidants ascorbate and glutathione. The activity of the ascorbate
      glutathione cycle enzymes was higher in mitochondria than in peroxisomes, except
      for APX, which was more active in peroxisomes than in mitochondria. Intact
      mitochondria and peroxisomes had no latent APX activity, and this remained in the
      membrane fraction after solubilization assays with 0.2 M KCl.
      Monodehydroascorbate reductase was highly latent in intact mitochondria and
      peroxisomes and was membrane-bound, suggesting that the electron acceptor and
      donor sites of this redox protein are not on the external side of the
      mitochondrial and peroxisomal membranes. Dehydroascorbate reductase was found
      mainly in the soluble peroxisomal and mitochondrial fractions. Glutathione
      reductase had a high latency in mitochondria and peroxisomes and was present in
      the soluble fractions of both organelles. In intact peroxisomes and mitochondria,
      the presence of reduced ascorbate and glutathione and the oxidized forms of
      ascorbate and glutathione were demonstrated by high-performance liquid
      chromatography analysis. The ascorbate-glutathione cycle of mitochondria and
      peroxisomes could represent an important antioxidant protection system against
      H2O2 generated in both plant organelles.

PMID- 12223705
TI  - The Expression of 2-Oxoglutarate/Malate Translocator in the Bundle-Sheath
      Mitochondria of Panicum miliaceum, a NAD-Malic Enzyme-Type C4 Plant, Is Regulated
      by Light and Development.
AB  - The bundle-sheath mitochondria in NAD-malic enzyme-type C4 plants participate in
      the C4 dicarboxylate cycle and require high capacities of translocators to
      accommodate the high rates of exchange of metabolites involved in photosynthesis.
      In Panicum miliaceum, a NAD-malic enzyme-type C4 plant, the steady-state level of
      mRNA for the mitochondrial 2-oxoglutarate (2-OG)/malate translocator was higher
      in leaves than in nonphotosynthetic tissues. Furthermore, the expression of the
      gene for the mitochondrial 2-OG/malate translocator was restricted to bundle
      sheath cells (BSC) but not mesophyll cells. The transcript level of the BSC
      located mitochondrial 2-OG/malate translocator increased during greening in
      accordance with levels of photosynthetic genes, although the relative transcript
      levels of other mitochondrial membrane proteins decreased. The specific
      activities of C4 photosynthetic enzymes and the relative abundance of the 2
      OG/malate translocator protein in bundle-sheath mitochondria increased in
      successive sections from the basal meristem to the distal tip, whereas the
      specific activities of mitochondrial respiratory enzymes remained constant or
      decreased. These findings indicate that the specific 2-OG/malate translocator in
      BSC mitochondria of P. miliaceum is expressed in concert with C4 enzymes during
      the differentiation of BSC and parallels the capacity of C4 photosynthesis. Most
      unusual, northern analysis showed that significant amounts of unspliced mRNAs,
      the levels of which are variable during greening, were present in leaf tissues.
      It is possible that this incomplete splicing is involved in posttranscriptional
      regulation of expression of this gene.

PMID- 12223707
TI  - Does Long-Term Elevation of CO2 Concentration Increase Photosynthesis in Forest
      Floor Vegetation? (Indiana Strawberry in a Maryland Forest).
AB  - As the partial pressure of CO2 (pCO2) in the atmosphere rises, photorespiratory
      loss of carbon in C3 photosynthesis will diminish and the net efficiency of light
      limited photosynthetic carbon uptake should rise. We tested this expectation for
      Indiana strawberry (Duchesnea indica) growing on a Maryland forest floor. Open
      top chambers were used to elevate the pCO2 of a forest floor habitat to 67 Pa and
      were paired with control chambers providing an ambient pCO2 of 38 Pa. After 3.5
      years, D. indica leaves grown and measured in the elevated pCO2 showed a
      significantly greater maximum quantum efficiency of net photosynthesis (by 22%)
      and a lower light compensation point (by 42%) than leaves grown and measured in
      the control chambers. The quantum efficiency to minimize photorespiration,
      measured in 1% O2, was the same for controls and plants grown at elevated pCO2.
      This showed that the maximum efficiency of light-energy transduction into
      assimilated carbon was not altered by acclimation and that the increase in light
      limited photosynthesis at elevated pCO2 was simply a function of the decrease in
      photorespiration. Acclimation did decrease the ribulose-1,5-bisphosphate
      carboxylase/oxygenase and light-harvesting chlorophyll protein content of the
      leaf by more than 30%. These changes were associated with a decreased capacity
      for light-saturated, but not light-limited, photosynthesis. Even so, leaves of D.
      indica grown and measured at elevated pCO2 showed greater light-saturated
      photosynthetic rates than leaves grown and measured at the current atmospheric
      pCO2. In situ measurements under natural forest floor lighting showed large
      increases in leaf photosynthesis at elevated pCO2, relative to controls, in both
      summer and fall. The increase in efficiency of light-limited photosynthesis with
      elevated pCO2 allowed positive net photosynthetic carbon uptake on days and at
      locations on the forest floor that light fluxes were insufficient for positive
      net photosynthesis in the current atmospheric pCO2.

PMID- 12223706
TI  - Sugar Repression of Mannitol Dehydrogenase Activity in Celery Cells.
AB  - We present evidence that the activity of the mannitol-catabolizing enzyme
      mannitol dehydrogenase (MTD) is repressed by sugars in cultured celery (Apium
      graveolens L.) cells. Furthermore, this sugar repression appears to be mediated
      by hexokinases (HKs) in a manner comparable to the reported sugar repression of
      photosynthetic genes. Glucose (Glc)-grown cell cultures expressed little MTD
      activity during active growth, but underwent a marked increase in MTD activity,
      protein, and RNA upon Glc starvation. Replenishment of Glc in the medium resulted
      in decreased MTD activity, protein, and RNA within 12 h. Addition of
      mannoheptulose, a competitive inhibitor of HK, derepressed MTD activity in Glc
      grown cultures. In contrast, the addition of the sugar analog 2-deoxyglucose,
      which is phosphorylated by HK but not further metabolized, repressed MTD activity
      in mannitol-grown cultures. Collectively, these data suggest that HK and sugar
      phosphorylation are involved in signaling MTD repression. In vivo repression of
      MTD activity by galactose (Gal), which is not a substrate of HK, appeared to be
      an exception to this hypothesis. Further analyses, however, showed that the
      products of Gal catabolism, Glc and fructose, rather than Gal itself, were
      correlated with MTD repression.

PMID- 12223708
TI  - Phase Separation of Plant Cell Wall Polysaccharides and Its Implications for Cell
      Wall Assembly.
AB  - Concentrated binary mixtures of polymers in solution commonly exhibit
      immiscibility, resolving into two separate phases each of which is enriched in
      one polymer. The plant cell wall is a concentrated polymer assembly, and phase
      separation of the constituent polymers could make an important contribution to
      its structural organization and functional properties. However, to our knowledge,
      there have been no published reports of the phase behavior of cell wall polymers,
      and this phenomenon is not included in current cell wall models. We fractionated
      cell walls purified from the pericarp of unripe tomatoes (Lycopersicon
      esculentum) by extraction with cyclohexane diamine tetraacetic acid (CDTA),
      Na2CO3, and KOH and examined the behavior of concentrated mixtures. Several
      different combinations of fractions exhibited phase separation. Analysis of
      coexisting phases demonstrated the immiscibility of the esterified, relatively
      unbranched pectic polysaccharide extracted by CDTA and a highly branched, de
      esterified pectic polysaccharide present in the 0.5 N KOH extract. Some evidence
      for phase separation of the CDTA extract and hemicellulosic polymers was also
      found. We believe that phase separation is likely to be a factor in the assembly
      of pectic polysaccharides in the cell wall and could, for example, provide the
      basis for explaining the formation of the middle lamella.

PMID- 12223709
TI  - Al-Induced, 51-Kilodalton, Membrane-Bound Proteins Are Associated with Resistance
      to Al in a Segregating Population of Wheat.
AB  - Incorporation of 35S into protein is reduced by exposure to Al in wheat (Triticum
      aestivum), but the effects are genotype-specific. Exposure to 10 to 75 [mu]M Al
      had little effect on 35S incorporation into total protein, nuclear and
      mitochondrial protein, microsomal protein, and cytosolic protein in the Al
      resistant cultivar PT741. In contrast, 10 [mu]M Al reduced incorporation by 21 to
      38% in the Al-sensitive cultivar Katepwa, with effects becoming more pronounced
      (31-62%) as concentrations of Al increased. We previously reported that a pair of
      51-kD membrane-bound proteins accumulated in root tips of PT741 under conditions
      of Al stress. We now report that the 51-kD band is labeled with 35S after 24 h of
      exposure to 75 [mu]M Al. The specific induction of the 51-kD band in PT741
      suggested a potential role of one or both of these proteins in mediating
      resistance to Al. Therefore, we analyzed their expression in single plants from
      an F2 population arising from a cross between the PT741 and Katepwa cultivars.
      Accumulation of 1,3-[beta]-glucans (callose) in root tips after 24 h of exposure
      to 100 [mu]M Al indicated that this population segregated for Al resistance in
      about a 3:1 ratio. A close correlation between resistance to Al (low callose
      content of root tips) and accumulation of the 51-kD band was observed, indicating
      that at least one of these proteins cosegregates with the Al-resistance
      phenotype. As a first step in identifying a possible function, we have
      demonstrated that the 51-kD band is most clearly associated with the tonoplast.
      Whereas Al has been reported to stimulate the activity of the tonoplast H+-ATPase
      and H+-PPase, antibodies raised against these proteins did not cross-react with
      the 51-kD band. Efforts are now under way to purify this protein from tonoplast
      enriched fractions.

PMID- 12223710
TI  - Pectin Modification in Cell Walls of Ripening Tomatoes Occurs in Distinct
      Domains.
AB  - The class of cell wall polysaccharides that undergoes the most extensive
      modification during tomato (Lycopersicon esculentum) fruit ripening is pectin. De
      esterification of the polygalacturonic acid backbone by pectin methylesterase
      facilitates the depolymerization of pectins by polygalacturonase II (PGII). To
      investigate the spatial aspects of the de-esterification of cell wall pectins and
      the subsequent deposition of PGII, we have used antibodies to relatively
      methylesterified and nonesterified pectic epitopes and to the PGII protein on
      thin sections of pericarp tissue at different developmental stages. De
      esterification of pectins and deposition of PGII protein occur in block-like
      domains within the cell wall. The boundaries of these domains are distinct and
      persistent, implying strict, spatial regulation of enzymic activities. Sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis of proteins strongly
      associated with cell walls of pericarp tissue at each stage of fruit development
      show ripening-related changes in this protein population. Western blots of these
      gels with anti-PGII antiserum demonstrate that PGII expression is ripening
      related. The PGII co-extracts with specific pectic fractions extracted with
      imidazole or with Na2CO3 at 0[deg]C from the walls of red-ripe pericarp tissue,
      indicating that the strong association between PGII and the cell wall involves
      binding to particular pectic polysaccharides.

PMID- 12223711
TI  - An Electron Paramagnetic Resonance Spin-Probe Study of Membrane-Permeability
      Changes with Seed Aging.
AB  - We developed an electron paramagnetic resonance spin-probe technique to study
      changes in the barrier properties of plasma membranes in wheat (Triticum aestivum
      L.) seeds during aging under dry storage. The estimation of these barrier
      properties was based on the differential permeability of membranes for the stable
      free radical 4-oxo-2,2,6,6-tetramethyl-1-piperidinyloxy and the broadening agent
      ferricyanide. The line-height ratio between the water and lipid components in the
      electron paramagnetic resonance spectra of 4-oxo-2,2,6,6-tetramethyl-1
      piperidinyloxy (R value) allowed for the quantitative assessment of the plasma
      membrane permeability in small samples, enabling separate studies of the axis,
      scutellum, aleurone layer, and starchy endosperm tissue. High R values
      corresponded to low permeability and vice versa. Starchy endosperm cells had
      completely permeable plasma membranes even in mature, viable seeds. The loss of
      germinability with aging coincided with a considerably increased plasma membrane
      permeability of the embryo axis cells, but not of the scutellum and aleurone
      layer cells. The threshold R value for the individual axes associated with
      viability loss was established at 5 to 6, with the total ranging from 0 to more
      than 12. We suggest that the R value of an individual axis is the result of
      contributions from all individual cells, each of them characterized by a
      different permeability. The loss of viability, therefore, corresponds to the
      accumulation of cells having permeability above a critical level.

PMID- 12223712
TI  - Carbon Isotopic Fractionation Does Not Occur during Dark Respiration in C3 and C4
      Plants.
AB  - The magnitude of possible carbon isotopic fractionation during dark respiration
      was investigated with isolated mesophyll cells from mature leaves of common bean
      (Phaseolus vulgaris L.), a C3 plant, and corn (Zea mays L.), a C4 plant.
      Mesophyll protoplasts were extracted from greenhouse-grown leaves and incubated
      in culture solutions containing different carbohydrate substrates (fructose,
      glucose, and sucrose) with known [delta]13C values. The CO2 produced by
      protoplasts after incubation in the dark was collected, purified, and analyzed
      for its carbon isotope ratio. From observations of the isotope ratios of the
      substrate and respired CO2, we calculated the carbon isotope discrimination
      associated with metabolism of each of these substrates. In eight of the 10
      treatment combinations, the carbon isotope ratio discrimination was not
      significantly different from 0. In the remaining two treatment combinations, the
      carbon isotope ratio discrimination was 1[per mille (thousand) sign]. From these
      results, we conclude that there is no significant carbon isotopic discrimination
      during mitochondrial dark respiration when fructase, glucose, or sucrose are used
      as respiratory substrates.

PMID- 12223713
TI  - Changing Technologies with a Constant Goal:Finding Out How Plants Function.

PMID- 12223714
TI  - Brefeldin A Effects in Plants (Are Different Golgi Responses Caused by Different
      Sites of Action?).

PMID- 12223715
TI  - Mechanism of Protein Transport across the Chloroplast Envelope.

PMID- 12223716
TI  - Importance of the Chiral Centers of Jasmonic Acid in the Responses of Plants
      (Activities and Antagonism between Natural and Synthetic Analogs).
AB  - The importance of the two chiral centers at C-3 and C-7 in the molecular
      structure of jasmonic acid in plant responses was investigated. We separated
      methyl jasmonate (MeJA) into (3R)- and (3S)-isomers with a fixed stereochemistry
      at C-3, but epimerization at C-7 is possible. The four isomers of the
      nonepimerizable analog 7-methyl MeJA were synthesized. These six esters and their
      corresponding acids were tested in three bioassays: (a) senescence in sunflower
      (Helianthus annuus) cotyledons; (b) proteinase inhibitor II gene expression in
      transgenic tobacco (Nicotiana tabacum) with [beta]-glucuronidase as a biochemical
      reporter; and (c) seed germination in Brassica napus and wheat (Triticum
      aestivum). The esters and acids had similar activities in the three assays, with
      the ester being more effective than its acid. The (3R)-stereochemistry was
      critical for jasmonate activity. Although activity was reduced after substituting
      the C-7 proton with a methyl group, the analogs with (3R,7R)- or (3R,7S)
      stereochemistry were active in some of the assays. Although the four isomers of 7
      methyl MeJA were inactive or only weakly active in the senescence assay, they
      could overcome the senescence-promoting effect of (3R)-MeJA. The strongest
      antagonistic effect was observed with the (3R,7S)-isomer.

PMID- 12223717
TI  - Tissue-Type-Specific Heat-Shock Response and Immunolocalization of Class I Low
      Molecular-Weight Heat-Shock Proteins in Soybean.
AB  - A monospecific polyclonal antibody was used to study the tissue-type specificity
      and intracellular localization of class I low-molecular-weight (LMW) heat-shock
      proteins (HSPs) in soybean (Glycine max) under different heat-shock regimes. In
      etiolated soybean seedlings, the root meristematic regions contained the highest
      levels of LMW HSP. No tissue-type-specific expression of class I LMW HSP was
      detected using the tissue-printing method. In immunolocalization studies of
      seedlings treated with HS (40[deg]C for 2 h) the class I LMW HSPs were found in
      the aggregated granular structures, which were distributed randomly in the
      cytoplasm and in the nucleus. When the heat shock was released, the granular
      structures disappeared and the class I LMW HSPs became distributed homogeneously
      in the cytoplasm. When the seedlings were then given a more severe heat shock
      following the initial 40[deg]C -> 28[deg]C treatment, a large proportion of the
      class I LMW HSPs that originally localized in the cytoplasm were translocated
      into the nucleus and nucleolus. Class I LMW HSPs may assist in the
      resolubilization of proteins denatured or aggregated by heat and may also
      participate in the restoration of organellar function after heat shock.

PMID- 12223718
TI  - The Two Forms of Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase Activase Differ
      in Sensitivity to Elevated Temperature.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase activase often consists of two
      polypeptides that arise from alternative splicing of pre-mRNA. In this study
      recombinant versions of the spinach (Spinacea oleracea L.) 45- and 41-kD forms of
      activase were analyzed for their response to temperature. The temperature optimum
      for ATP hydrolysis by the 45-kD form was 45[deg]C, approximately 13[deg]C higher
      than the 41-kD form. When the two forms were mixed, the temperature response of
      the hybrid enzyme was similar to the 45-kD form. In the absence of adenine
      nucleotide, preincubation of either activase form at temperatures above 25[deg}C
      inactivated ATPase activity. Adenosine 5[prime]-([gamma]-thio)triphosphate, but
      not ADP, significantly enhanced the thermostability of the 45-kD form but was
      much less effective for the 41-kD form. Intrinsic fluorescence showed that the
      adenosine 5[prime]-([gamma]-thio)triphosphate-induced subunit aggregation was
      lost at a much lower temperature for the 41-kD than for the 45-kD form. However,
      the two activase forms were equally susceptible to limited proteolysis after heat
      treatment. The results indicate that (a) the 45-kD form is more thermostable
      than, and confers increased thermal stability to, the 41-kD form, and (b) a loss
      of subunit interactions, rather than enzyme denaturation, appears to be the
      initial cause of temperature inactivation of activase.

PMID- 12223719
TI  - Putrescine Aminopropyltransferase Is Responsible for Biosynthesis of Spermidine,
      Spermine, and Multiple Uncommon Polyamines in Osmotic Stress-Tolerant Alfalfa.
AB  - The biosynthesis of polyamines from the diamine putrescine is not fully
      understood in higher plants. A putrescine aminopropyltransferase (PAPT) enzyme
      activity was characterized in alfalfa (Medicago sativa L.). This enzyme activity
      was highly specific for putrescine as the initial substrate and did not recognize
      another common diamine, 1,3-diaminopropane, or higher-molecular-weight polyamines
      such as spermidine and spermine as alternative initial substrates. The enzyme
      activity was inhibited by a general inhibitor of aminopropyltransferases,
      5[prime]-methylthioadenosine, and by a specific inhibitor of PAPTs,
      cyclohexylammonium sulfate. The initial substrate specificity and inhibition
      characteristics of the enzyme activity suggested that it is a classical example
      of a PAPT. However, this enzyme activity yielded multiple polyamine products,
      which is uncharacteristic of PAPTs. The major reaction product of PAPT activity
      in alfalfa was spermidine. The next most abundant products of the enzyme reaction
      using putrescine as the initial substrate included the tetramines spermine and
      thermospermine. These two tetramines were distinguished by thin-layer
      chromatography to be distinct reaction products exhibiting differential rates of
      formation. In addition, the uncommon polyamines homocaldopentamine and
      homocaldohexamine were tentatively identified as minor enzymatic reaction
      products but only in extracts prepared from osmotic stresstolerant alfalfa
      cultivars. PAPT activity from alfalfa was highest in meristematic shoot tip and
      floral bud tissues and was not detected in older, nonmeristematic tissues.
      Product inhibition of the enzyme activity was observed after spermidine was added
      into the in vitro assay for alfalfa PAPT activity. A biosynthetic pathway is
      proposed that accounts for the characteristics of this PAPT activity and
      accommodates a novel scheme by which certain uncommon polyamines are produced in
      plants.

PMID- 12223720
TI  - Cold Acclimation and Freezing Tolerance (A Complex Interaction of Light and
      Temperature).
AB  - By comparing growth under five different temperature and irradiance regimes
      (20[deg]C and 800, 250, and 50[mu]mol m-2 s-1 and 5[deg]C and 250 and 50 [mu]mul
      m-2 s-1), we have examined the effects of light, temperature, and the relative
      reduction state of photosystem II on plant morphology, freezing tolerance (lethal
      temperature at which freezing injury occurs [LT50]), transcript levels of Lhcb
      and two cold-stimulated genes (Wcs19 and Wcs120), and photosynthetic adjustment
      in winter rye (Secale cereale L. cv Musketeer). We show, for the first time to
      our knowledge, that in addition to adjustments in photosynthetic capacity,
      nonphotochemical quenching capacity and tolerance to photoinhibition, the
      accumulation of the cold-induced transcript Wcs19, and the compact plant
      morphology usually associated with cold-hardening are correlated with the
      relative reduction state of photosystem II rather than with growth temperature or
      growth irradiance per se. In contrast, the acquisition of maximal LT50, as well
      as Lhcb and Wcs120 mRNA accumulation, appears to be dependent on both growth
      temperature and growth irradiance but in an independent, additive manner. The
      results are discussed with respect to the possible role of the modulation of
      chloroplastic redox poise in photosynthetic acclimation to cold-hardening
      temperatures and the attainment of maximal LT50.

PMID- 12223721
TI  - Influence of Environmental Stress on Biomass Partitioning in Transgenic Tobacco
      Plants Expressing the Movement Protein of Tobacco Mosaic Virus.
AB  - The influence of various environmental factors on biomass partitioning between
      shoots and roots in transgenic tobacco (Nicotiana tabacum) plants expressing the
      movement protein (MP) of tobacco mosaic virus (TMV) was investigated. TMV-MP
      expressing transgenic plants exhibited a root-to-shoot ratio that was
      approximately 40% below that of transgenic vector control plants. When transgenic
      plants expressing the TMV-MP were subjected to water-stress conditions, the root
      to-shoot ratio was increased to a value comparable to that of control plants
      subjected to the same water-stress treatment. Although the root-to-shoot ratio
      was increased by N or P deficiencies, the TMV-MP-induced alteration in biomass
      partitioning was not overcome. Surprisingly, under K+-deficient growth
      conditions, both TMV-MP-expressing and control plants exhibited reduced root-to
      shoot ratios when compared with plants grown in the presence of sufficient K+.
      Furthermore, plant growth under K+-deficient conditions did not alleviate the
      influence of the TMV-MP over resource allocation to the roots. These results are
      discussed in terms of possible mechanisms by which stress signals could cause an
      alteration in biomass partitioning between shoots and roots in control and
      transgenic tobacco plants expressing the TMV-MP.

PMID- 12223722
TI  - Does Decrease in Ribulose-1,5-Bisphosphate Carboxylase by Antisense RbcS Lead to
      a Higher N-Use Efficiency of Photosynthesis under Conditions of Saturating CO2
      and Light in Rice Plants?
AB  - Rice (Oryza sativa L.) plants with decreased ribulose-1,5-bisphosphate
      carboxylase (Rubisco) were obtained by transformation with the rice rbcS
      antisense gene under the control of the rice rbcS promoter. The primary
      transformants were screened for the Rubisco to leaf N ratio, and the transformant
      with 65% wild-type Rubisco was selected as a plant set with optimal Rubisco
      content at saturating CO2 partial pressures for photosynthesis under conditions
      of high irradiance and 25[deg]C. This optimal Rubisco content was estimated from
      the amounts and kinetic constants of Rubisco and the gas-exchange data. The R1
      selfed progeny of the selected transformant were grown hydroponically with
      different N concentrations. Rubisco content in the R1 population was distributed
      into two groups: 56 plants had about 65% wild-type Rubisco, whereas 23 plants
      were very similar to the wild type. Although the plants with decreased Rubisco
      showed 20% lower rates of light-saturated photosynthesis in normal air (36 Pa
      CO2), they had 5 to 15% higher rates of photosynthesis in elevated partial
      pressures of CO2, (100-115 Pa CO2) than the wild-type plants for a given leaf N
      content. We conclude that the rice plants with 65% wild-type Rubisco show a
      higher N-use efficiency of photosynthesis under conditions of saturating CO2 and
      high irradiance.

PMID- 12223723
TI  - Decreased Growth-Induced Water Potential (A Primary Cause of Growth Inhibition at
      Low Water Potentials).
AB  - Cell enlargement depends on a growth-induced difference in water potential to
      move water into the cells. Water deficits decrease this potential difference and
      inhibit growth. To investigate whether the decrease causes the growth inhibition,
      pressure was applied to the roots of soybean (Glycine max L. Merr.) seedlings and
      the growth and potential difference were monitored in the stems. In water-limited
      plants, the inhibited stem growth increased when the roots were pressurized and
      it reverted to the previous rate when the pressure was released. The pressure
      around the roots was perceived as an increased turgor in the stem in small cells
      next to the xylem, but not in outlying cortical cells. This local effect implied
      that water transport was impeded by the small cells. The diffusivity for water
      was much less in the small cells than in the outlying cells. The small cells thus
      were a barrier that caused the growth-induced potential difference to be large
      during rapid growth, but to reverse locally during the early part of a water
      deficit. Such a barrier may be a frequent property of meristems. Because stem
      growth responded to the pressure-induced recovery of the potential difference
      across this barrier, we conclude that a decrease in the growth-induced potential
      difference was a primary cause of the inhibition.

PMID- 12223724
TI  - Metabolic Control of Avocado Fruit Growth (Isoprenoid Growth Regulators and the
      Reaction Catalyzed by 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase).
AB  - The effect of isoprenoid growth regulators on avocado (Persea americana Mill. cv
      Hass) fruit growth and mesocarp 3-hydroxy-3-methylglutaryl coenzyme A reductase
      (HMGR) activity was investigated during the course of fruit ontogeny. Both normal
      and small-fruit phenotypes were used to probe the interaction between the end
      products of isoprenoid biosynthesis and the activity of HMGR in the metabolic
      control of avocado fruit growth. Kinetic analysis of the changes in both cell
      number and size revealed that growth was limited by cell number in phenotypically
      small fruit. In small fruit a 70% reduction in microsomal HMGR activity was
      associated with an increased mesocarp abscisic acid (ABA) concentration.
      Application of mevastatin, a competitive inhibitor of HMGR, reduced the growth of
      normal fruit and increased mesocarp ABA concentration. These effects were
      reversed by co-treatment of fruit with mevalonic acid lactone,
      isopentenyladenine, or N-(2-chloro-4-pyridyl)-N-phenylurea, but were not
      significantly affected by either gibberellic acid or stigmasterol. However,
      stigmasterol appeared to partially restore fruit growth when co-injected with
      mevastatin in either phase II or III of fruit growth. In vivo application of ABA
      reduced fruit growth and mesocarp HMGR activity and accelerated fruit abscission,
      effects that were reversed by co-treatment with isopentenyladenine. Together,
      these observations indicate that ABA accumulation down-regulates mesocarp HMGR
      activity and fruit growth, and that in situ cytokinin biosynthesis modulates
      these effects during phase I of fruit ontogeny, whereas both cytokinins and
      sterols seem to perform this function during the later phases.

PMID- 12223725
TI  - Effect of Water Stress on Cortical Cell Division Rates within the Apical Meristem
      of Primary Roots of Maize.
AB  - We characterized the effect of water stress on cell division rates within the
      meristem of the primary root of maize (Zea mays L.) seedlings. As usual in growth
      kinematics, cell number density is found by counting the number of cells per
      small unit length of the root; growth velocity is the rate of displacement of a
      cellular particle found at a given distance from the apex; and the cell flux,
      representing the rate at which cells are moving past a spatial point, is defined
      as the product of velocity and cell number density. The local cell division rate
      is estimated by summing the derivative of cell density with respect to time, and
      the derivative of the cell flux with respect to distance. Relatively long (2-h)
      intervals were required for time-lapse photography to resolve growth velocity
      within the meristem. Water stress caused meristematic cells to be longer and
      reduced the rates of cell division, per unit length of tissue and per cell,
      throughout most of the meristem. Peak cell division rate was 8.2 cells mm-1 h-1
      (0.10 cells cell-1 h-1) at 0.8 mm from the apex for cells under water stress,
      compared with 13 cells mm-1 h-1 (0.14 cells cell-1 h-1) at 1.0 mm for controls.

PMID- 12223726
TI  - Overproduction of Ascorbate Peroxidase in the Tobacco Chloroplast Does Not
      Provide Protection against Ozone.
AB  - Transgenic tobacco (Nicotiana tabacum cv Bel W3) plants were used to test the
      hypothesis that protection from O3 injury could be conferred by overproduction of
      ascorbate peroxidase (APX) in the chloroplast. The 10-fold increase in soluble
      APX activity in the chloroplast was expected to alleviate an implied increase in
      oxidative potential and prevent damage caused by O3. Three different O3 exposure
      experiments (one acute and two chronic) with two replicates each were conducted.
      APX activity in nontransgenic plants increased in response to chronic O3
      exposure. However, most responses to O3 were similar between transgenic and
      nontransgenic plants. These included reductions in net photosynthesis and
      stomatal conductance, increases in ethylene emission and visible injury, and a
      decline in the level of the small subunit of ribulose-1,5-biphosphate
      carboxylase/oxygenase mRNA transcripts observed in response to the air pollutant
      in the acute and/or chronic experiments. No O3-induced effect on ribulose-1,5
      biphosphate carboxylase/oxygenase quantity was observed in the chronic
      experiments. O3 did not induce acceleration of senescence, as expected from
      studies with most other species; rather, the tobacco plants rapidly developed
      necrotic lesions. Thus, overproduction of APX in the chloroplast did not protect
      this cultivar of tobacco from O3.

PMID- 12223727
TI  - Characterization of the Cell Wall Microdomain Surrounding Plasmodesmata in Apple
      Fruit.
AB  - In fleshy fruits ripening is generally associated with a loss in tissue firmness
      resulting from depolymerization of wall components and separation of adjacent
      cells. In the regions of the wall that contain plasmodesmata, the usual sequences
      of ripening events, i.e. depolymerization of the middle lamellae and splitting of
      the walls, are not observed. In the present study we attempted to characterize in
      apple (Malus domestica Borkh.) fruit the structural microdomain of the cell wall
      that surrounds the plasmodesmata by in muro visualization of the cell wall
      components. Anionic sites of galacturonic acids were labeled with cationic gold.
      Low-esterified homogalacturonans were labeled with the monoclonal antibody JIM 5.
      In addition, a polyclonal antibody directed toward [beta](1->3)-glucopyranose was
      used to target callose in situ. The results indicated that the plasmodesmata-wall
      complexes were surrounded by a pectic microdomain. This domain was composed of
      low-esterified homogalacturonans that were not involved in calcium cross-bridging
      but were probably surrounded by a cationic environment. These structural features
      may result in the prevention of normal cell wall separation in regions containing
      plasmodesmata. However, observations by low-temperature scanning electron
      microscopy suggested that splitting of these walls ruptured the plasmodesmata and
      ultimately resulted in the spatial separation of adjacent cells.

PMID- 12223728
TI  - Pollination Increases Gibberellin Levels in Developing Ovaries of Seeded
      Varieties of Citrus.
AB  - Reproductive and vegetative tissues of the seeded Pineapple cultivars of sweet
      orange (Citrus sinensis L.) contained the following C-13 hydroxylated
      gibberellins (GAs): GA53, GA17, GA19, GA20, GA1, GA29, and GA8, as well as GA97,
      3-epi-GA1, and several uncharacterized GAs. The inclusion of 3-epi-GA1 as an
      endogenous substance was based on measurements of the isomerization rates of
      previously added [2H2]GA1. Pollination enhanced amounts of GA19, GA20, GA29, and
      GA8 in developing ovaries. Levels of GA1 increased from 5.0 to 9.5 ng/g dry
      weight during anthesis and were reduced thereafter. The amount of GA in mature
      pollen was very low. Emasculation reduced GA levels and caused a rapid 100% ovary
      abscission. This effect was partially counteracted by either pollination or
      application of GA3. In pollinated ovaries, repeated paclobutrazol applications
      decreased the amount of GA and increased ovary abscission, although the pattern
      of continuous decline was different from the sudden abscission induced by
      emasculation. The above results indicate that, in citrus, pollination increases
      GA levels and reduces ovary abscission and that the presence of exogenous GA3 in
      unpollinated ovaries also suppresses abscission. Evidence is also presented that
      pollination and GAs do not, as is generally assumed, suppress ovary abscission
      through the reactivation of cell division.

PMID- 12223729
TI  - Purification and Characterization of Allene Oxide Cyclase from Dry Corn Seeds.
AB  - Allene oxide cyclase (AOC; EC 5.3.99.6) catalyzes the cyclization of 12,13(S)
      epoxy-9(Z),11,15(Z)-octadecatrienoic acid to 12-oxo- 10,15(Z)-phytodienoic acid,
      the precursor of jasmonic acid (JA). This soluble enzyme was purified 2000-fold
      from dry corn (Zea mays L.) kernels to apparent homogeneity. The dimeric protein
      has a molecular mass of 47 kD. Allene oxide cyclase activity was not affected by
      divalent ions and was not feedback-regulated by its product, 12-oxo-l0,15(Z)
      phytodienoic acid, or by JA. ([plus or minus])-cis- 12,13-Epoxy-9(Z)-octadecenoic
      acid, a substrate analog, strongly inhibited the enzyme, with 50% inhibition at
      20 [mu]M. Modification of the inhibitor, such as methylation of the carboxyl
      group or a shift in the position of the epoxy group, abolished the inhibitory
      effect, indicating that both structural elements and their position are essential
      for binding to AOC. Nonsteroidal anti-inflammatory drugs, which are often used to
      interfere with JA biosynthesis, did not influence AOC activity. The purified
      enzyme catalyzed the cyclization of 12,13(S)-epoxy-9(Z),11,15(Z)-octadecatrienoic
      acid derived from linolenic acid, but not that of 12,13(S)-epoxy-9(Z),11-
      octadecadienoic acid derived from linoleic acid.

PMID- 12223730
TI  - Regulation of the Accumulation and Reduction of Nitrate by Nitrogen and Carbon
      Metabolites in Maize Seedlings.
AB  - The accumulation and reduction of nitrate in the presence of the nitrogen
      metabolites asparagine (Asn) and glutamine (Gln) and the carbon metabolite
      sucrose (Suc) were examined in maize (Zea mays L.) seedlings in an attempt to
      separate their effects on the nitrate uptake system and the nitrate reduction
      system. After 8 h of exposure to nitrate in the presence of 1 mM Asn, tissue
      nitrate accumulation was reduced at 250 [mu]M external nitrate, but not at 5 mM
      Asn. The induction of nitrate reductase (NR) activity was reduced at both
      external nitrate concentrations. In the presence of 1 mM Gln or 1% Suc, tissue
      nitrate concentration was not significantly altered, but the induction of root NR
      activity was reduced or enhanced, respectively. The induction of root nitrite
      reductase (NiR) activity was also reduced in the presence of Asn or Gln and
      enhanced in the presence of Suc. Transcript levels of NR and NiR in roots were
      reduced in the presence of the amides and enhanced in the presence of Suc. When
      Suc was present in combination with either amide, there was complete relief from
      the inhibition of NiR transcription observed in the presence of amide alone. In
      the case of NR, however, this relief from inhibition was negligible. The
      inhibition of the induction of NR and NiR activities in the presence of Gln and
      Asn is a direct effect and is not the result of altered nitrate uptake in the
      presence of these metabolites.

PMID- 12223731
TI  - ATP Hydrolysis Activity and Polymerization State of Ribulose-1,5-Bisphosphate
      Carboxylase Oxygenase Activase (Do the Effects of Mg2+, K+, and Activase
      Concentrations Indicate a Functional Similarity to Actin?).
AB  - The ATPase activity and fluoresence of ribulose-1,5-bisphosphate carboxylase
      oxygenase (Rubisco) activase were determined over a range of MgCl2, KCl, and
      activase concentrations. Both salts promoted ADP release from ATP and intrinsic
      fluorescence enhancement by adenosine 5[prime]-[[gamma]-thio] triphosphate, but
      Mg2+ was about 10 times more effective than K+. ATPase and fluorescence
      enhancement both increased from zero to saturation within the same Mg2+ and K+
      concentration ranges. At saturating concentrations (5 mM Mg2+ and 22 mM K+), the
      specific activity of ATPase (turnover time, about 1 s) and specific intrinsic
      fluorescence enhancement were maximal and unaffected by activase concentration
      above 1 [mu]M activase; below 1 [mu]M activase, both decreased sharply. These
      responses are remarkably similar to the behavior of actin. Intrinsic fluorescence
      enhancement of Rubisco activase reflects the extent of polymerization, showing
      that the smaller oligomer or monomer present in low-salt and activase
      concentrations is inactive in ATP hydrolysis. However, quenching of 1
      anilinonapthaline-8-sulfonate fluorescence revealed that ADP and adenosine
      5[prime]-[[gamma]-thio] triphosphate bind equally well to activase at low- and
      high-salt concentrations. This is consistent with an actin-like mechanism
      requiring a dynamic equilibrium between monomer and oligomers for ATP hydrolysis.
      The specific activation rate of substrate-bound decarbamylated Rubisco decreased
      at activase concentrations below 1 [mu]M. This suggests that a large oligomeric
      form of activase, rather than a monomer, interacts with Rubisco when performing
      the release of bound ribulose-1,5-bisphosphate from the inactive enzyme.

PMID- 12223732
TI  - Physiological and Biochemical Response of the Photosynthetic Apparatus of Two
      Marine Diatoms to Fe Stress.
AB  - Flavodoxin is a small electron-transfer protein capable of replacing ferredoxin
      during periods of Fe deficiency. When evaluating the suitability of flavodoxin as
      a diagnostic indicator for Fe limitation of phytoplankton growth, we examined its
      expression in two marine diatoms we cultured using trace-metal-buffered medium.
      Thalassio-sira weissflogii and Phaeodactylum tricornutum were cultured in
      ethylenediaminetetraacetic acid-buffered Sargasso Sea water containing from 10 to
      1000 nM added Fe. Trace-metal-buffered cultures of each diatom maintained high
      growth rates across the entire range of Fe additions. Similarly, declines in
      chlorophyll/cell and in the ratio of photosystem II variable-to-maximum
      fluorescence were negligible (P. tricornutum) to moderate (T. weissflogii; 54%
      decline in chlorophyll/cell and 22% decrease in variable-to-maximum
      fluorescence). Moreover, only minor variations in photosynthetic parameters were
      observed across the range of additions. In contrast, flavodoxin was expressed to
      high levels in low-Fe cultures. Despite the inverse relationship between
      flavodoxin expression and Fe content of the medium, its expression was seemingly
      independent of any of the indicators of cell physiology that were assayed. It
      appears that flavodoxin is expressed as an early-stage response to Fe stress and
      that its accumulation need not be intimately connected to limitations imposed by
      Fe on the growth rate of these diatoms.

PMID- 12223733
TI  - Nutrients, Signals, and Photosynthate Release by Symbiotic Algae (The Impact of
      Taurine on the Dinoflagellate Alga Symbiodinium from the Sea Anemone Aiptasia
      pulchella).
AB  - Exogenous concentrations of 10 [mu]M to 1 mM of the nonprotein amino acid taurine
      stimulated photosynthate release from the dinoflagellate alga Symbiodinium, which
      had been freshly isolated from the sea anemone Aiptasia pulchella. Photosynthate
      release, as induced by taurine and animal extract, was metabolically equivalent
      at both concentrations in that they (a) stimulated photosynthate release to the
      same extent and (b) induced the selective release of photosynthetically derived
      organic acids. A complex mixture of amino acids at 75 mM also promoted
      photosynthate release, but the release rate was reduced by 34% after the omission
      of taurine (3 mM) from the mixture, suggesting that much of the effect of amino
      acids was largely attributable to taurine. Exogenous 14C-labeled taurine was
      taken up by the cells, and more than 95% of the internalized 14C was recovered as
      taurine, indicating that taurine-induced photosynthate release was not dependent
      on taurine metabolism. Both taurine uptake and taurine-induced photosynthate
      release by Symbiodinium exhibited saturation kinetics, but with significantly
      different Km values of 68 and 21 [mu]M, respectively. The difference in Km values
      is compatible with the hypothesis that Symbiodinium has a taurine signal
      transducer that is responsible for photosynthate release and is distinct from the
      taurine transporter.

PMID- 12223734
TI  - A Xyloglucan-Specific Endo-1,4-[beta]-Glucanase Isolated from Auxin-Treated Pea
      Stems.
AB  - A xyloglucan-specific endo-1,4-[beta]-glucanase was isolated from the apoplast
      fraction of auxin-treated pea (Pisum sativum) stems, in which both the rate of
      stem elongation and the amount of xyloglucan solubilized were high. The enzyme
      was purified to apparent homogeneity by sequential cation-exchange
      chromatographies, affinity chromatography, and gel filtration. The purified
      enzyme gave a single protein band on sodium dodecyi sulfate-polyacrylamide gel
      electrophoresis, and the molecular size was determined to be 77 kD by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and 70 kD by gel filtration.
      The isoelectric point was about 8.1. The enzyme specifically cleaved the 1,4
      [beta]-glucosyl linkages of the xyloglucan backbone to yield mainly nona- and
      heptasaccharides but did not hydrolyze carboxymethylcellulose, swollen cellulose,
      and (1->3, 1->4)-[beta]-glucan. By hydrolysis, the average molecular size of
      xyloglucan was decreased from 50 to 20 kD with new reducing chain ends in the
      lower molecular size fractions. This suggests that the enzyme has endo-1,4-[beta]
      glucanase activity against xyloglucan. In conclusion, a xyloglucan-specific endo
      1,4-[beta]-glucanase with an activity that differs from the activities of
      cellulase and xyloglucan endotransglycosylase has been isolated from elongating
      pea stems.

PMID- 12223735
TI  - Differential Induction of Lipoxygenase Isoforms in Wheat upon Treatment with Rust
      Fungus Elicitor, Chitin Oligosaccharides, Chitosan, and Methyl Jasmonate.
AB  - A glycopeptide elicitor prepared from germ tubes of the rust fungus Puccinia
      graminis Pers. f. sp. tritici Erikss. & Henn (Pgt), as well as chitin
      oligosaccharides, chitosan, and methyl jasmonate (MJ) stimulated lipoxygenase
      (LOX) activity (E.C. 1.13.11.12) in wheat (Triticum aestivum) leaves. Immunoblot
      analysis using anti-LOX antibodies revealed the induction of 92- and 103-kD LOX
      species after Pgt elicitor treatment. In contrast, MJ treatment led to a
      significant increase of a 100-kD LOX species, which was also detected at lower
      levels in control plants. The effects of chitin oligomers and chitosan resembled
      those caused by MJ. In conjunction with other observations the results suggest
      that separate reaction cascades exist, and that jasmonates may not be involved in
      Pgt elicitor action. LOX-92 appears to be mainly responsible for the increase in
      LOX activity after Pgt elicitor treatment because its appearance on western blots
      coincided with high LOX activity in distinct anion-exchange chromatography
      fractions. It is most active at pH 5.5 to 6.0, and product formation from
      linoleic and [alpha]-linolenic acid is clearly in favor of the 9-LOOHs. It is
      interesting that a 92-kD LOX species, which seems to correspond to the Pgt
      elicitor-induced LOX species, was also detected in rust-inoculated leaves.

PMID- 12223736
TI  - Allocation of S in Generative Growth of Soybean.
AB  - Soybean plants (Glycine max L. Merr) were grown with 100 [mu]M S and 15 mM N and
      studied with respect to S allocation during grain development. The grains
      accounted for 87% of the S taken up after d 42, the balance coming from internal
      redistribution of S from leaves and pods. Detailed studies of the leaves, pods,
      and grains associated with leaf axils 6 and 7 showed that sulfate accumulated in
      the pods as they expanded to 50% of full length, ahead of grain enlargement, but
      declined to very low levels as grain growth commenced. Conversely,
      homoglutathione (hGSH), cysteine, and methionine increased. In developing grains,
      hGSH accounted for 60 to 90% of the soluble-S but sulfate was barely detectable.
      The data are consistent with a model in which, under S-limiting conditions, the
      pods act as sinks for sulfate and grain growth initiates the assimilation of
      sulfate into hGSH in the pods, and then into developing grains, where it is
      incorporated into grain proteins.

PMID- 12223737
TI  - Changes in Activities of Antioxidant Enzymes and Their Relationship to Genetic
      and Paclobutrazol-Induced Chilling Tolerance of Maize Seedlings.
AB  - The potential role of antioxidant enzymes in protecting maize (Zea mays L.)
      seedlings from chilling injury was examined by analyzing enzyme activities and
      isozyme profiles of chilling-susceptible (CO 316) and chilling-tolerant (CO 328)
      inbreds. Leaf superoxide dismutase (SOD) activity in CO 316 was nearly one-half
      that of CO 328, in which the high activity was maintained during the chilling and
      postchilling periods. Activity of glutathione reductase (GR) was much higher in
      roots than in leaves. CO 328 also possessed a new GR isozyme that was absent in
      roots of CO 316. Ascorbate peroxidase (APX) activity was considerably lower in
      leaves of CO 328 than in CO 316, and nearly similar in roots. Paclobutrazol
      treatment of CO 316 induced several changes in the antioxidant enzyme profiles
      and enhanced their activities, especially those of SOD and APX, along with the
      induction of chilling tolerance. These results suggest that increased activities
      of SOD in leaves and GR in roots of CO 328, as well as SOD and APX in leaves and
      roots of paclobutrazol-treated CO 316, contribute to their enhanced chilling
      tolerance.

PMID- 12223738
TI  - Subcellular Localization of Secondary Lipid Metabolites Including Fragrance
      Volatiles in Carnation Petals.
AB  - Pulse-chase labeling of carnation (Dianthus caryophyllus L. cv Improved White
      Sim) petals with [14C]acetate has provided evidence for a hydrophobic
      subcompartment of lipid-protein particles within the cytosol that resemble oil
      bodies, are formed by blebbing from membranes, and are enriched in lipid
      metabolites (including fragrance volatiles) derived from membrane fatty acids.
      Fractionation of the petals during pulse-chase labeling revealed that
      radiolabeled fatty acids appear first in microsomal membranes and subsequently in
      cytosolic lipid-protein particles, indicating that the particles originate from
      membranes. This interpretation is supported by the finding that the cytosolic
      lipid-protein particles contain phospholipid as well as the same fatty acids
      found in microsomal membranes. Radiolabeled polar lipid metabolites
      (methanol/water-soluble) were detectable in both in situ lipid-protein particles
      isolated from the cytosol and those generated in vitro from isolated radiolabeled
      microsomal membranes. The lipid-protein particles were also enriched in hexanal,
      trans-2-hexenal, 1-hexanol, 3-hexen-1-ol, and 2-hexanol, volatiles of carnation
      flower fragrance that are derived from membrane fatty acids through the
      lipoxygenase pathway. Therefore, secondary lipid metabolites, including
      components of fragrance, appear to be formed within membranes of petal tissue and
      are subsequently released from the membrane bilayers into the cytosol by blebbing
      of lipid-protein particles.

PMID- 12223739
TI  - A Plant Chloroplast Glutamyl Proteinase.
AB  - A glutamyl proteinase was partially purified from Percoll gradient-purified
      spinach (Spinacia oleracea) chloroplast preparations and appeared to be
      predominantly localized in the chloroplast stroma. The enzyme degraded casein,
      but of the 11 synthetic endopeptidase substrates tested, only benzyloxycarbonyl
      leucine-leucine-glutamic acid-[beta]-napthylamide was hydrolyzed at measurable
      rates. In addition, the enzyme cleaved the oxidized [beta]-chain of insulin after
      a glutamic acid residue. There was no evidence that native ribulose-1,5
      bisphosphate carboxylase/oxygenase was cleaved by this proteinase. The apparent
      Km for benzyloxycarbonyl-leucine-leucine-glutamic acid-[beta]NA at the pH optimum
      of 8.0 was about 1 mM. Cl-ions were required for both activity and stability. Of
      the proteinase inhibitors covering all four classes of the endopeptidases, only 4
      (2-aminoethyl)-benzenesulfonyl-fluoride HCl and L-1-chloro-3-[4-tosylamido]-4
      phenyl-2-butanone significantly inhibited the proteinase. The partially purified
      enzyme had a molecular weight of about 350,000 to 380,000, based on size
      exclusion chromatography. The enzyme has both similar and distinctive properties
      to those of the bacterial glutamyl proteinases. To our knowledge, this is the
      first description of a plant glutamyl proteinase found predominantly or
      exclusively in the chloroplast.

PMID- 12223740
TI  - Turnover of Galactans and Other Cell Wall Polysaccharides during Development of
      Flax Plants.
AB  - We investigated the synthesis and turnover of cell wall polysaccharides of the
      flax (Linum usitatissimum L.) plant during development of the phloem fibers. One
      month-old flax plants were exposed to a 40-min pulse with 14CO2 followed by 8-h,
      24-h, and 1-month periods of chase with ambient CO2, and radioactivity in cell
      wall sugars was determined in various plant parts. The relative radioactivity of
      glucose in noncellulosic polysaccharides was the highest compared with all other
      cell wall sugars immediately after the pulse and decreased substantially during
      the subsequent chase. The relative radioactivities of the other cell wall sugars
      changed with differing rates, indicating turnover of specific polysaccharides.
      Notably, after 1 month of chase there was a marked decrease in the proportional
      mass and total radioactivity in cell wall galactose, indicating a long-term
      turnover of the galactans enriched in the fiber-containing tissues. The ratio of
      radiolabeled xylose to arabinose also increased during the chase, indicating a
      turnover of arabinose-containing polymers and interconversion to xylose. The
      pattern of label redistribution differed between organs, indicating that the cell
      wall turnover processes are tissue- and cell-specific.

PMID- 12223741
TI  - The Mechanism of Amino Acid Efflux from Seed Coats of Developing Pea Seeds as
      Revealed by Uptake Experiments.
AB  - The uptake of amino acids by excised seed coat halves of developing seeds of pea
      (Pisum sativum L.) was characterized. The influx of L-valine and L-glutamic acid
      was proportional to their external concentration, with coefficients of
      proportionality (k) of 11.0 and 7.1 [mu]mol g-1 fresh weight min-1 M-1,
      respectively. The influx of L-lysine could be analyzed into a component with
      linear kinetics (k = 8.1 [mu]mol g-1 fresh weight min-1 M-1) and one with
      saturation kinetics (Michaelis constant = 6.5 mM), but the latter may have
      resulted from the mutual interaction between the influx of the cationic lysine
      and the membrane potential. The influx of the amino acids was not affected by 10
      [mu]M carbonylcyanide m-chlorophenylhydrazone, but was inhibited by about 50% in
      the presence of 2.5 mM p-chloromercuribenzene sulfonic acid. Conservative
      estimates of the permeability coefficients of the plasma membrane of seed coat
      parenchyma cells for lysine, glutamic acid, and several neutral amino acids were
      all in the range of 4 x 10-7 cm s-1 to 9 x 10-7 cm s-1, which is 4 to 5 orders of
      magnitude greater than those reported for artificial lipid bilayers. It is
      concluded that nonselective pores constitute a pathway in the plasma membrane for
      passive transport of amino acids. It is argued that this pathway is also used for
      the efflux of endogenous amino acids, the process by which nitrogen becomes
      available for the embryo.

PMID- 12223742
TI  - Dissecting the Diphenylene Iodonium-Sensitive NAD(P)H:Quinone Oxidoreductase of
      Zucchini Plasma Membrane.
AB  - Quinone oxidoreductase activities dependent on pyridine nucleotides are
      associated with the plasma membrane (PM) in zucchini (Cucurbita pepo L.)
      hypocotyls. In the presence of NADPH, lipophilic ubiquinone homologs with up to
      three isoprenoid units were reduced by intact PM vesicles with a Km of 2 to 7
      [mu]M. Affinities for both NADPH and NADH were similar (Km of 62 and 51 [mu]M,
      respectively). Two NAD(P)H:quinone oxidoreductase forms were identified. The
      first, labeled as peak I in gel-filtration experiments, behaves as an intrinsic
      membrane complex of about 300 kD, it slightly prefers NADH over NADPH, it is
      markedly sensitive to the inhibitor diphenylene iodonium, and it is active with
      lipophilic quinones. The second form (peak II) is an NADPH-preferring
      oxidoreductase of about 90 kD, weakly bound to the PM. Peak II is diphenylene
      iodonium-insensitive and resembles, in many properties, the soluble
      NAD(P)H:quinone oxidoreductase that is also present in the same tissue. Following
      purification of peak I, however, the latter gave rise to a quinone oxidoreductase
      of the soluble type (peak II), based on substrate and inhibitor specificities and
      chromatographic and electrophoretic evidence. It is proposed that a redox protein
      of the same class as the soluble NAD(P)H:quinone oxidoreductase (F. Sparla, G.
      Tedeschi, and P. Trost [1996] Plant Physiol. 112:249-258) is a component of the
      diphenylene iodonium-sensitive PM complex capable of reducing lipophilic
      quinones.

PMID- 12223743
TI  - C4 Gene Expression in Photosynthetic and Nonphotosynthetic Leaf Regions of
      Amaranthus tricolor.
AB  - Throughout most of its growth and development, Amaranthus tricolor produces fully
      green leaves. However, near the onset of flowering, unique leaves emerge that
      consist of three distinct color regions: green apices, yellow middle regions, and
      red basal regions. The green apices are identical to fully green leaves in terms
      of pigment composition, photosynthetic function, and C4 gene expression. The
      yellow and red regions possess greatly reduced levels of chlorophyll and they
      lack photosynthetic activity. The absence of photosynthetic capacity in the
      nongreen leaf regions was associated with three distinct alterations in C4 gene
      expression. First, there was a reduction in the translation of C4 polypeptides,
      and in the yellow regions synthesis of the ribulose-1,5-bisphosphate carboxylase
      small subunit occurred in the absence of large subunit synthesis. Second, there
      was a reduction in the relative transcription rates of two plastid-encoded
      photosynthetic genes, rbcL and psbA. Third, there was a loss of bundle-sheath
      cell-specific accumulation of the rbcL and RbcS mRNAs (but not the polypeptides,
      which remained bundle-sheath-specific). This study indicates that alterations in
      photosynthetic activity or developmental processes responsible for the loss of
      activity can influence C4 gene expression at multiple regulatory levels.

PMID- 12223744
TI  - Experimental Analysis of Tassel Development in the Maize Mutant Tassel Seed 6.
AB  - The maize (Zea mays L.) mutation Tassel seed 6 (Ts6) disrupts both sex
      determination in the tassel and the pattern of branching in inflorescences. This
      results in the formation of supernumerary florets in tassels and ears and in the
      development of pistils in tassel florets where they are normally aborted. A
      developmental analysis indicated that extra florets in Ts6 inflorescences are
      most likely the result of delayed determinacy in spikelet meristems, which then
      initiate additional floret meristems rather than initiating floral organs as in
      wild type. I have used culturing experiments to assay whether delayed determinacy
      of Ts6 mutant tassels is reflected in an altered timing of specific determination
      events. Length of the tassel was used as a developmental marker. These
      experiments showed that although Ts6 tassels elongate much more slowly than wild
      type, both mutant and wild-type tassels gained the ability to form flowers with
      organs of normal morphology in culture at the same time. In situ hybridization
      patterns of expression of the maize gene Kn, which is normally expressed in shoot
      meristems and not in determinate lateral organs, confirmed that additional
      meristems, rather than lateral organs, are initiated by spikelet meristems in Ts6
      tassels.

PMID- 12223745
TI  - Increased Expression of Vacuolar Aquaporin and H+-ATPase Related to Motor Cell
      Function in Mimosa pudica L.
AB  - Mature motor cells of Mimosa pudica that exhibit large and rapid turgor
      variations in response to external stimuli are characterized by two distinct
      types of vacuoles, one containing large amounts of tannins (tannin vacuole) and
      one without tannins (colloidal or aqueous vacuole). In these highly specialized
      cells we measured the abundance of two tonoplast proteins, a putative water
      channel protein (aquaporin belonging to the [gamma]-TIPs [tonoplast intrinsic
      proteins]) and the catalytic A-subunit of H+-ATPase, using either high-pressure
      freezing or chemical fixation and immunolocalization. [gamma]-TIP aquaporin was
      detected almost exclusively in the tonoplast of the colloidal vacuole, and the H+
      ATPase was also mainly localized in the membrane of the same vacuole. Cortex
      cells of young pulvini cannot change shape rapidly. Development of the pulvinus
      into a motor organ was accompanied by a more than 3-fold increase per length unit
      of membrane in the abundance of both aquaporin and H+-ATPase cross-reacting
      protein. These results indicate that facilitated water fluxes across the vacuolar
      membrane and energization of the vacuole play a central role in these motor
      cells.

PMID- 12223746
TI  - Mitochondrial Respiration and Hemoglobin Gene Expression in Barley Aleurone
      Tissue.
AB  - Previous studies have shown that plant hemoglobin (Hb) mRNA is expressed in
      barley (Hordeum vulgare L.) aleurone layers during hypoxia. We have examined the
      effect of a number of respiratory inhibitors on barley aleurone layers to
      determine the factors that influence Hb gene expression. Respiratory inhibitors
      that reduce O2 consumption, such as CO, cyanide, and antimycin A, strongly
      enhanced Hb mRNA levels. Treatment with the oxidative phosphorylation uncoupler
      2,4-dinitrophenol markedly increased O2 consumption and had a similar positive
      effect on Hb gene expression. Hb transcript levels were also stimulated by the
      ATP synthase inhibitor oligomycin. The results suggest that the expression of Hb
      is not directly influenced by O2 usage or availability but is influenced by the
      availability of ATP in the tissue.

PMID- 12223747
TI  - Evidence That a Malate/Inorganic Phosphate Exchange Translocator Imports Carbon
      across the Leucoplast Envelope for Fatty Acid Synthesis in Developing Castor Seed
      Endosperm.
AB  - In this study we examined the processes by which malate and pyruvate are taken up
      across the leucoplast envelope for fatty acid synthesis in developing castor
      (Ricinus communis L.) seed endosperm. Malate was taken up by isolated leucoplasts
      with a concentration dependence indicative of protein-mediated transport. The
      maximum rate of malate uptake was 704 [plus or minus] 41 nmol mg-1 protein h-1
      and the Km was 0.62 [plus or minus] 0.08 mM. In contrast, the rate of pyruvate
      uptake increased linearly with respect to the substrate concentration and was 5
      fold less than malate at a concentration of 5 mM. Malate uptake was inhibited by
      inorganic phosphate (Pi), glutamate, malonate, succinate, 2-oxoglutarate, and n
      butyl malonate, an inhibitor of the mitochondrial malate/Pi-exchange
      translocator. Back-exchange experiments confirmed that malate was taken up by
      leucoplasts in counterexchange for Pi. The exchange stoichiometry was 1:1. The
      rate of malate-dependent fatty acid synthesis by isolated leucoplasts was 3-fold
      greater than from pyruvate at a concentration of 5 mM and was inhibited by n
      butyl malonate. It is proposed that leucoplasts from developing castor endosperm
      contain a malate/Pi translocator that imports malate for fatty acid synthesis.
      This type of dicarboxylate transport activity has not been identified previously
      in plastids.

PMID- 12223748
TI  - Structural Characterization of Modified Lignin in Transgenic Tobacco Plants in
      Which the Activity of 4-Coumarate:Coenzyme A Ligase Is Depressed.
AB  - Transgenic tobacco (Nicotiana tabacum L.) plants in which the activity of 4
      coumarate:coenzyme A ligase is very low contain a novel lignin in their xylem.
      Details of changes in hydroxycinnamic acids bound to cell walls and in the
      structure of the novel lignin were identified by base hydrolysis, alkaline
      nitrobenzene oxidation, pyrolysis-gas chromatography, and 13C-nuclear magnetic
      resonance analysis. In the brownish tissue of the transgenic plants, the levels
      of three hydroxycinnamic acids, p-coumaric, ferulic, and sinapic, which were
      bound to cell walls, were apparently increased as a result of down-regulation of
      the expression of the gene for 4-coumarate:coenzyme A ligase. Some of these
      hydroxycinnamic acids were linked to cell walls via ester and ether linkages. The
      accumulation of hydroxycinnamic acids also induced an increase in the level of
      condensed units in the novel lignin of the brownish tissue. Our data indicate
      that the behavior of some of the incorporated hydroxycinnamic acids resembles
      lignin monomers in the brownish tissue, and their accumulation results in
      dramatic changes in the biosynthesis of lignin in transgenic plants.

PMID- 12223749
TI  - Involvement of Thylakoid Overenergization in Tentoxin-Induced Chlorosis in
      Nicotiana spp.
AB  - The purpose of this work was to clarify the mechanism of tentoxin-induced
      chlorosis in Nicotiana spp. seedlings. We found that chlorosis does not correlate
      with the inhibition of chloroplast ATP synthesis in vivo, since it occurs at
      tentoxin concentrations far higher than that required for the inhibition of
      photophosphorylation measured in the same seedlings. However, tentoxin-induced
      chlorosis does correlate with in vivo overenergization of thylakoids. We show
      that tentoxin induces overenergization in intact plants and isolated thylakoids,
      probably via multiple interactions with ATP synthase. Furthermore, gramicidin D,
      a protonophore that relieves overenergization, also relieves chlorosis. Two lines
      of evidence suggest that reactive oxygen species may be involved in the process
      of chlorosis: ascorbate, a quencher of oxygen radicals, significantly protects
      against chlorosis, whereas transgenic Nicotiana spp. mutants overexpressing
      chloroplast superoxide dismutase are partially resistant to tentoxin-induced
      chlorosis. It is proposed that chlorosis in developing seedlings results from
      overenergization of thylakoids, which leads to the generation of oxygen radicals.

PMID- 12223750
TI  - Control of Leaf Expansion Rate of Droughted Maize Plants under Fluctuating
      Evaporative Demand (A Superposition of Hydraulic and Chemical Messages?).
AB  - We have analyzed the possibility that chemical signaling does not entirely
      account for the effect of water deficit on the maize (Zea mays L.) leaf
      elongation rate (LER) under high evaporative demand. We followed time courses of
      LER (0.2-h interval) and spatial distribution of elongation rate in leaves of
      either water-deficient or abscisic acid (ABA)-fed plants subjected to varying
      transpiration rates in the field, in the greenhouse, and in the growth chamber.
      At low transpiration rates the effect of the soil water status on LER was related
      to the concentration of ABA in the xylem sap and could be mimicked by feeding
      artificial ABA. Transpiring plants experienced a further reduction in LER,
      directly linked to the transpiration rate or leaf water status. Leaf zones
      located at more than 20 mm from the ligule stopped expanding during the day and
      renewed expansion during the night. Neither ABA concentration in the xylem sap,
      which did not appreciably vary during the day, nor ABA flux into shoots could
      account for the effect of evaporative demand. In particular, maximum LER was
      observed simultaneously with a minimum ABA flux in the droughted plants, but with
      a maximum ABA flux in ABA-fed plants. All data were interpreted as the
      superposition of two additive effects: the first involved ABA signaling and was
      observed during the night and in ABA-fed plants, and the second involved the
      transpiration rate and was observed even in well-watered plants. We suggest that
      a hydraulic signal is the most likely candidate for this second effect.

PMID- 12223751
TI  - Tris Is a Competitive Inhibitor of K+ Activation of the Vacuolar H+-Pumping
      Pyrophosphatase.
AB  - The effects of a range of commonly used pH buffers on the hydrolytic activity of
      the plant vacuolar H+-transporting inorganic pyrophosphatase (V-PPase) from mung
      bean (Vigna radiata L.) hypocotyls were tested. All of the buffers inhibited K+
      stimulation of the V-PPase, and the degree of inhibition was dependent on the
      concentrations of both the buffer and K+. The effects were dependent on the
      organic cation used in the buffers, and those tested inhibited in the order: Tris
      > Bis-Tris-propane > Bicine = Tricine > imidazole. Detailed studies revealed that
      a model in which Tris affects both the Km and Vmax for K+ stimulation provided an
      accurate description of the observed kinetics. The ability of different cations
      to stimulate the V-PPase was measured with a noncompeting buffer (5 mM imidazole
      HCl) and the order of effectiveness was K+ = Rb+ > NH4+ >> Cs+ > Na+ > Li+, with
      the Km for K+ stimulation being about 1 to 2 mM. Published experiments performed
      in the presence of Tris were re-evaluated and all could be fitted to mixed
      inhibition kinetics, with kinetic parameters similar to those measured for the
      mung bean V-PPase. It is concluded that the variations in the published Km for K+
      stimulation of the V-PPase are probably due to the effects of pH buffer cations
      and that the real value for this parameter is in the low millimolar range. The
      implications of this for regulation of the V-PPase by K+ in vivo and for the role
      of the enzyme in K+ transport into the vacuole are discussed.

PMID- 12223752
TI  - Biochemical Characterization and Subcellular Localization of the Red Kidney Bean
      Purple Acid Phosphatase.
AB  - Phosphatases are known to play a crucial role in phosphate turnover in plants.
      However, the exact role of acid phosphatases in plants has been elusive because
      of insufficient knowledge of their in vivo substrate and subcellular
      localization. We investigated the biochemical properties of a purple acid
      phosphatase isolated from red kidney bean (Phaseolus vulgaris) (KBPAP) with
      respect to its substrate and inhibitor profiles. The kinetic parameters were
      estimated for five substrates. We used 31P nuclear magnetic resonance to
      investigate the in vivo substrate of KBPAP. Chemical and enzymological estimation
      of polyphosphates and ATP, respectively, indicated the absence of polyphosphates
      and the presence of ATP in trace amounts in the seed extracts. Immunolocalization
      using antibodies raised against KBPAP was unsuccessful because of the non
      specificity of the antiserum toward glycoproteins. Using histoenzymological
      methods with ATP as a substrate, we could localize KBPAP exclusively in the cell
      walls of the peripheral two to three rows of cells in the cotyledons. KBPAP
      activity was not detected in the embryo. In vitro experiments indicated that
      pectin, a major component of the cell wall, significantly altered the kinetic
      properties of KBPAP. The substrate profile and localization suggest that KBPAP
      may have a role in mobilizing organic phosphates in the soil during germination.

PMID- 12223753
TI  - Modulation of Dehydration Tolerance in Soybean Seedlings (Dehydrin Mat1 Is
      Induced by Dehydration but Not by Abscisic Acid).
AB  - Germinated soybean (Glycine max L. cv Williams 82) seedlings subjected to rapid
      dehydration begin to lose the ability to recover when the relative water content
      of the plant decreases below 60%. The expanded cells of the hypocotyl appear more
      susceptible to dehydration-induced damage than do cells in the hypocotyl zone of
      cell growth. Pretreatment of seedlings prior to rapid dehydration with nonlethal
      water deficit or exogenous abscisic acid (ABA) shifts this viability threshold to
      progressively lower relative water contents, indicating the acquisition of
      increased dehydration tolerance. Increased tolerance is associated with osmotic
      adjustment in the hypocotyl zone of cell growth and with increases in soybean
      dehydrin Mat1 mRNA levels. The accumulation of Mat1 mRNA is dehydration dependent
      but insensitive to ABA. Induction of Mat1 mRNA accumulation by dehydration but
      not by ABA makes it an unusual member of the dehydrin family.

PMID- 12223754
TI  - Stress-Induced Declines in Soybean N2 Fixation Are Related to Nodule Sucrose
      Synthase Activity.
AB  - Soybean (Glycine max L.) plants were subjected to a number of treatments
      (drought, 10 mM nitrate, 150 mM NaCl, shoot meristem removal, and removal of
      approximately 50% of the nodules) to test the hypothesis that metabolic responses
      contribute to the regulation of N2 fixation. Nitrogenase activity was correlated
      with the activity of nodule sucrose synthase (SS), but not with that of glutamine
      oxoglutarate amino transferase. Leghemoglobin levels and other enzyme activities
      were not significantly or consistently affected by the treatments. SS mRNA was
      greatly reduced in nodules of drought-, salt-, and nitrate-treated plants;
      however, this was not correlated with changes in soluble carbohydrate, starch,
      amino acids, or ureides. Leghemoglobin mRNA was only slightly affected by the
      treatments. The time course of drought stress showed a decline in the SS
      transcript level by 1 d, but levels of leghemoglobin, glutamine synthetase, and
      ascorbate peroxidase mRNA were not markedly affected by 4 d. SS activity at 4 d
      was reduced by 46%. We propose that N2 fixation in soybean nodules is mediated by
      both the oxygen-diffusion barrier and the potential to metabolize sucrose via SS.
      The response to environmental perturbation may involve down-regulation of the
      nodule SS gene.

PMID- 12223755
TI  - Wound-Induced Changes of Membrane Voltage, Endogenous Currents, and Ion Fluxes in
      Primary Roots of Maize.
AB  - The effects of mechanical wounding on membrane voltage, endogenous ion currents,
      and ion fluxes were investigated in primary roots of maize (Zea mays) using
      intracellular microelectrodes, a vibrating probe, and ion-selective electrodes.
      After a wedge-shaped wound was cut into the proximal elongation zone of the
      roots, a large inward current of approximately 60 [mu]A cm-2 was measured,
      together with a change in the current pattern along the root. The changes of the
      endogenous ion current were accompanied by depolarization of the membrane voltage
      of cortex cells up to 5 mm from the wound. Neither inhibitors of ion channels nor
      low temperature affected the large, wound-induced inward current. The fluxes of
      H+, K+, Ca2+, and Cl- contributed only about 7 [mu]A cm-2 to the wound-induced
      ion current. This suggests the occurrence of a large mass flow of negatively
      charged molecules, such as proteins, sulfated polysaccharides, and galacturonic
      acids, from the wound. Natural wounding of the root cortex by developing lateral
      roots caused an outwardly directed current, which was clearly different in
      magnitude and direction from the current induced by mechanical injury.

PMID- 12223756
TI  - Blue-Light-Induced Shrinking of Protoplasts from Maize Coleoptiles and Its
      Relationship to Coleoptile Growth.
AB  - Protoplasts isolated from red-light-grown maize (Zea mays L.) coleoptiles shrank
      transiently upon brief exposure (e.g. 30 s) to blue light under background
      irradiation with red light. The maximal volume reduction (about 4% at a
      saturating fluence) occurred about 5 min after blue-light stimulation. The
      response was prevented by the anion-channel blocker 5-nitro-2-(3
      phenylpropylamino)-benzoic acid. Red light and far-red light did not induce any
      comparable response. Protoplasts of different sizes and those isolated from
      different coleoptile positions showed similar responses. After treatment with a
      saturating blue-light pulse, the protoplasts became responsive to a second pulse
      and gained full responsiveness within 5 min, suggesting that the photoreceptor
      system involves a dark-reversible component. The response to continuous blue
      light was also found to be transient. The protoplast volume was reduced during
      about 6 to 9 min of irradiation and returned within the next 30 min to the
      control level. The response to continuous blue light was saturated at 30 [mu]mol
      m-2 s-1. However, when the fluence rate was enhanced 10-fold after a period of
      irradiation at 30 [mu]mol m-2 s-1, the protoplasts showed another shrinking
      response. These and other kinetic results indicate that the photoreceptor system
      undergoes a photosensory adaptation. Growth in different zones of the coleoptile
      was inhibited by blue light transiently after pulse stimulation, as well as
      during continuous stimulation. It was concluded that the observed protoplast
      shrinking is related to the blue-light-induced inhibition of coleoptile growth.

PMID- 12223757
TI  - Differential Localization of Antioxidants in Maize Leaves.
AB  - The aim of this work was to determine the compartmentation of antioxidants
      between the bundle-sheath and mesophyll cells of maize (Zea mays L.) leaves.
      Rapid fractionation of the mesophyll compartment was used to minimize
      modifications in the antioxidant status and composition due to extraction
      procedures. The purity of the mesophyll isolates was assessed via the
      distribution of enzyme and metabolite markers. Ribulose-1,5 bisphosphate and
      ribulose-1,5-bisphosphate carboxylase/oxygenase were used as bundle-sheath
      markers and phosphoenolpyruvate carboxylase was used as the mesophyll marker
      enzyme. Glutathione reductase and dehydroascorbate reductase were almost
      exclusively localized in the mesophyll tissue, whereas ascorbate, ascorbate
      peroxidase, and superoxide dismutase were largely absent from the mesophyll
      fraction. Catalase, reduced glutathione, and monodehydroascorbate reductase were
      found to be approximately equally distributed between the two cell types. It is
      interesting that, whereas H2O2 levels were relatively high in maize leaves, this
      oxidant was largely restricted to the mesophyll compartment. We conclude that the
      antioxidants in maize leaves are partitioned between the two cell types according
      to the availability of reducing power and NADPH and that oxidized glutathione and
      dehydroascorbate produced in the bundle-sheat tissues have to be transported to
      the mesophyll for re-reduction to their reduced forms.

PMID- 12223758
TI  - Effect of Chilling on Carbon Assimilation, Enzyme Activation, and Photosynthetic
      Electron Transport in the Absence of Photoinhibition in Maize Leaves.
AB  - The relationships between electron transport and photosynthetic carbon metabolism
      were measured in maize (Zea mays L.) leaves following exposure to suboptimal
      temperatures. The quantum efficiency for electron transport in unchilled leaves
      was similar to that previously observed in C3 plants, although maize has two
      types of chloroplasts, mesophyll and bundle sheath, with PSII being largely
      absent from the latter. The index of noncyclic electron transport was
      proportional to the CO2 assimilation rate. Chilled leaves showed decreased rates
      of CO2 assimilation relative to unchilled leaves, but the integral relationships
      between the quantum efficiency for electron transport or the index of noncyclic
      electron transport and CO2 fixation were unchanged and there was no
      photoinhibition. The maximum catalytic activities of the Benson-Calvin cycle
      enzymes, fructose-1,6-bisphosphatase and ribulose-1,5-bisphosphate carboxylase,
      were decreased following chilling, but activation was unaffected. Measurements of
      thiol-regulated enzymes, particularly NADP-malate dehydrogenase, indicated that
      chilling induced changes in the stromal redox state so that reducing equivalents
      were more plentiful. We conclude that chilling produces a decrease in
      photosynthetic capacity without changing the internal operational, regulatory or
      stoichiometric relationships between photosynthetic electron transport and carbon
      assimilation. The enzymes of carbon assimilation are particularly sensitive to
      chilling, but enhanced activation may compensate for decreases in maximal
      catalytic activity.

PMID- 12223759
TI  - Maternal, Single-Gene Regulation of Assimilate Partitioning in Pea.
AB  - Assimilate partitioning has been identified as a key process in the control of
      yield. Although the role of reproductive structures in this process has received
      intensive study, our understanding of the role of the maternal plant is limited.
      We suggest that the Sn gene of pea (Pisum sativum L.) is a potentially valuable
      genetic tool for studying maternal regulation of partitioning. In this study,
      nearly isogenic lines differing at the Sn locus were compared with respect to
      seed-filling characteristics and carbon assimilation. Lines with the Sn gene had
      a slower rate and shorter duration of seed growth than the line recessive for
      this gene, and these traits could not be ascribed to reduced carbon assimilation.
      Flowers of the two nearly isogenic lines were manually pollinated to control the
      genotype of the developing embryo independently of the maternal genotype. The
      final dry weight of the seed was determined by the genotype of the maternal plant
      and not by the genotype of the embryo, supporting the hypothesis that the Sn gene
      acts in the vegetative plant to regulate the partitioning of assimilates between
      vegetative and reproductive growth. Although the Sn gene has been noted for
      delaying apical senescence, it also delayed leaf senescence in this study; leaves
      of the Sn line continued to photosynthesize long past the time that leaves of the
      recessive line had senesced and after the seeds and pods were dry.

PMID- 12223760
TI  - Induction of the Root Cell Plasma Membrane Ferric Reductase (An Exclusive Role
      for Fe and Cu).
AB  - Induction of ferric reductase activity in dicots and nongrass monocots is a well
      recognized response to Fe deficiency. Recent evidence has shown that Cu
      deficiency also induces plasma membrane Fe reduction. In this study we
      investigated whether other nutrient deficiencies could also induce ferric
      reductase activity in roots of pea (Pisum sativum L. cv Sparkle) seedlings. Of
      the nutrient deficiencies tested (K, Mg, Ca, Mn, Zn, Fe, and Cu), only Cu and Fe
      deficiencies elicited a response. Cu deficiency induced an activity intermediate
      between Fe-deficient and control plant activities. To ascertain whether the same
      reductase is induced by Fe and Cu deficiency, concentration- and pH-dependent
      kinetics of root ferric reduction were compared in plants grown under control, 
      Fe, and -Cu conditions. Additionally, rhizosphere acidification, another process
      induced by Fe deficiency, was quantified in pea seedlings grown under the three
      regimes. Control, Fe-deficient, and Cu-deficient plants exhibited no major
      differences in pH optima or Km for the kinetics of ferric reduction. However, the
      Vmax for ferric reduction was dramatically influenced by plant nutrient status,
      increasing 16- to 38-fold under Fe deficiency and 1.5- to 4-fold under Cu
      deficiency, compared with that of control plants. These results are consistent
      with a model in which varying amounts of the same enzyme are deployed on the
      plasma membrane in response to plant Fe or Cu status. Rhizosphere acidification
      rates in the Cu-deficient plants were similarly intermediate between those of the
      control and Fe-deficient plants. These results suggest that Cu deficiency induces
      the same responses induced by Fe deficiency in peas.

PMID- 12223761
TI  - [beta]-1,3-Glucanase Is Cryoprotective in Vitro and Is Accumulated in Leaves
      during Cold Acclimation.
AB  - We have used isolated spinach (Spinacea oleracea L.) thylakoid membranes to
      investigate the possible cryoprotective properties of class I [beta]-1,3
      glucanase (1,3-[beta]-D-glucan 3-glucanohydrolase; EC 3.2.1.39) and chitinase.
      Class I [beta]-1,3-glucanase that was purified from tobacco (Nicotiana tabacum
      L.) protected thylakoids against freeze-thaw injury in our in vitro assays,
      whereas class I chitinase from tobacco had no effect under the same conditions.
      The [beta]-1,3-glucanase acted by reducing the influx of solutes into the
      membrane vesicles during freezing and thereby reduced osmotic stress and vesicle
      rupture during thawing. Western blots probed with antibodies directed against
      tobacco class I [beta]-1,3-glucanase showed that in spinach and cabbage (Brassica
      oleracea L.) leaves an isoform of 41 kD was accumulated during frost hardening
      under natural conditions.

PMID- 12223762
TI  - Expression of Pokeweed Antiviral Protein in Transgenic Plants Induces Virus
      Resistance in Grafted Wild-Type Plants Independently of Salicylic Acid
      Accumulation and Pathogenesis-Related Protein Synthesis.
AB  - Pokeweed antiviral protein (PAP), a 29-kD protein isolated from Phytolacca
      americana, inhibits translation by catalytically removing a specific adenine
      residue from the large rRNA of the 60S subunit of eukaryotic ribosomes.
      Transgenic tobacco (Nicotiana tabacum) plants expressing PAP or a variant (PAP-v)
      were shown to be resistant to a broad spectrum of plant viruses. Expression of
      PAP-v in transgenic plants induces synthesis of pathogenesis-related proteins and
      a very weak (<2-fold) increase in salicylic acid levels. Using reciprocal
      grafting experiments, we demonstrate here that transgenic tobacco rootstocks
      expressing PAP-v induce resistance to tobacco mosaic virus infection in both N.
      tabacum NN and nn scions. Increased resistance to potato virus X was also
      observed in N. tabacum nn scions grafted on transgenic rootstocks. PAP expression
      was not detected in the wild-type scions or rootstocks that showed virus
      resistance, nor was there any increase in salicylic acid levels or pathogenesis
      related protein synthesis. Grafting experiments with transgenic plants expressing
      an inactive PAP mutant demonstrated that an intact active site of PAP is
      necessary for induction of virus resistance in wild-type scions. These results
      indicate that enzymatic activity of PAP is responsible for generating a signal
      that renders wild-type scions resistant to virus infection in the absence of
      increased salicylic acid levels and pathogenesis-related protein synthesis.

PMID- 12223763
TI  - De Novo Biosynthesis of Volatiles Induced by Insect Herbivory in Cotton Plants.
AB  - In response to insect feeding on the leaves, cotton (Gossypium hirsutum L.)
      plants release elevated levels of volatiles, which can serve as a chemical signal
      that attracts natural enemies of the herbivore to the damaged plant. Pulse
      labeling experiments with [13C]CO2 demonstrated that many of the volatiles
      released, including the acyclic terpenes (E,E)-[alpha]-farnesene, (E)-[beta]
      farnesene, (E)-[beta]-ocimene, linalool, (E)-4,8-dimethyl-1,3,7-nonatriene, and
      (E/E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene, as well as the shikimate pathway
      product indole, are biosynthesized de novo following insect damage. However,
      other volatile constituents, including several cyclic terpenes, butyrates, and
      green leaf volatiles of the lipoxygenase pathway are released from storage or
      synthesized from stored intermediates. Analysis of volatiles from artificially
      damaged plants, with and without beet armyworm (Spodoptera exigua Hubner) oral
      secretions exogenously applied to the leaves, as well as volatiles from beet
      armyworm-damaged and -undamaged control plants, demonstrated that the application
      of caterpillar oral secretions increased both the production and release of
      several volatiles that are synthesized de novo in response to insect feeding.
      These results establish that the plant plays an active and dynamic role in
      mediating the interaction between herbivores and natural enemies of herbivores.

PMID- 12223764
TI  - ZEA3: A Negative Modulator of Cytokinin Responses in Plant Seedlings.
AB  - In Nicotiana plumbaginifolia cytokinins affect seedling development by inhibiting
      root growth and hypocotyl elongation and by stimulating cotyledon expansion. The
      zea3.1 mutant was selected for its inability to grow in conditions of low
      nitrogen and for its ability to grow independently on inhibitory concentrations
      of zeatin (J.D. Faure, M. Jullien, M. Caboche [1994] Plant J 5: 481-491). The
      zea3.1 growth response to cytokinins is reflected by an increase in cotyledon
      expansion due to cell division and by a swelling of the hypocotyl due to cell
      enlargement. An analysis of the seedling's root length and fresh weight over a
      wide range of benzyladenine concentrations showed that zea3.1 plants exhibit a
      higher sensitivity and an amplified response to cytokinins. A similar response of
      zea3.1 to benzyladenine was also seen in the expression of msr1, a cytokinin
      regulated gene. Regulation of msr1 expression by protein phosphorylation was
      unaffected by the zea3.1 mutation. No significant differences in cytokinin and
      auxin levels were found between zea3.1 and wild-type seedlings, suggesting that
      the mutant phenotype is not caused by an alteration of these hormone levels. The
      data presented suggest that ZEA3 negatively modulates cytokinin responses and may
      function as a broad regulator of seedling development.

PMID- 12223765
TI  - Characterization of Antisense Transformed Plants Deficient in the Tobacco Anionic
      Peroxidase.
AB  - On the basis of the biological compounds that they metabolize, plant peroxidases
      have long been implicated in plant growth, cell wall biogenesis, lignification,
      and host defenses. Transgenic tobacco (Nicotiana tabacum L.) plants that
      underexpress anionic peroxidase were generated using antisense RNA. The antisense
      RNA was found to be specific for the anionic isoenzyme and highly effective,
      reducing endogenous transcript levels and total peroxidase activity by as much as
      1600-fold. Antisense-transformed plants appeared normal at initial observation;
      however, growth studies showed that plants with reduced peroxidase activity grow
      taller and flower sooner than control plants. In contrast, previously transformed
      plants overproducing anionic peroxidase were shorter and flowered later than
      controls. Axillary buds were more developed in antisense-transformed plants and
      less developed in plants overproducing this enzyme. It was found that the lignin
      content in leaf, stem, and root was unchanged in antisense-transformed plants,
      which does not support a role for anionic peroxidase in the lignification of
      secondary xylem vessels. However, studies of wounded tissue show some reduction
      in wound-induced deposition of lignin-like polymers. The data support a possible
      role for tobacco anionic peroxidase in host defenses but not without a reduction
      in growth potential.

PMID- 12223766
TI  - Differential Gene Expression in Response to Auxin Treatment in the Wild Type and
      rac, an Adventitious Rooting-Incompetent Mutant of Tobacco.
AB  - Histological analyses of auxin-treated cuttings from the wild type and the rac
      mutant of tobacco (Nicotiana tabacum cv Xanthii) previously revealed that some
      rac phloem parenchyma or inner cortical parenchyma cells form callus in response
      to exogenous auxin treatment but these cells never undergo the organized
      divisions associated with adventitious root initiation in the wild type. Here we
      report the effect of the rac mutation on the temporal and spatial expression
      patterns of three genes previously shown to be associated with adventitious root
      meristems, HRGPnt3, iaa4/5, and gh3. Using histochemical staining analyses of
      HRGPnt3-GUS transformant cuttings, we determined that the rac mutation blocks
      auxin activation of the HRGPnt3 promoter. Thus, activation of the HRGPnt3
      promoter occurs specifically during adventitious root initiation in tobacco
      cuttings. Histochemical staining analyses of iaa4/5-GUS and gh3-GUS transformant
      cuttings revealed that the rac mutation does not repress the auxin activation of
      the iaa4/5 and gh3 promoters. Based on our histochemical staining analyses, we
      conclude that differential gene expression occurs in response to auxin treatment
      during adventitious root initiation in the wild type compared with callus
      formation in rac cuttings. We also determined that HRGPnt3 mRNA accumulation
      occurs in response to components of our root-induction protocol other than auxin,
      indicating that HRGPnt3 expression is regulated both developmentally and
      environmentally.

PMID- 12223767
TI  - Al Inhibits Both Shoot Development and Root Growth in als3, an Al-Sensitive
      Arabidopsis Mutant.
AB  - In als3, an Al-sensitive Arabidopsis mutant, shoot development and root growth
      are sensitive to Al. Mutant als3 seedlings grown in an Al-containing medium
      exhibit severely inhibited leaf expansion and root growth. In the presence of Al,
      unexpanded leaves accumulate callose, an indicator of Al damage in roots. The
      possibility that the inhibition of shoot development in als3 is due to the
      hyperaccumulation of Al in this tissue was examined. However, it was found that
      the levels of Al that accumulated in shoots of als3 are not different from the
      wild type. The inhibition of shoot development in als3 is not a consequence of
      nonspecific damage to roots, because other metals (e.g. LaCl3 or CuSO4) that
      strongly inhibit root growth did not block shoot development in als3 seedlings.
      Al did not block leaf development in excised als3 shoots grown in an Al
      containing medium, demonstrating that the Al-induced damage in als3 shoots was
      dependent on the presence of roots. This suggests that Al inhibition of als3
      shoot development may be a delocalized response to Al-induced stresses in roots
      following Al exposure.

PMID- 12223768
TI  - Pea Mutants with Reduced Sensitivity to Far-Red Light Define an Important Role
      for Phytochrome A in Day-Length Detection.
AB  - In garden pea (Pisum sativum L.), a long-day plant, long photoperiods promote
      flowering by reducing the synthesis or transport of a graft-transmissible
      inhibitor of flowering. Previous physiological studies have indicated that this
      promotive effect is predominantly achieved through a response that requires long
      exposures to light and for which far-red (FR) light is the most effective. These
      characteristics implicate the action of phytochrome A (phyA). To investigate this
      matter further, we screened ethylmethane sulfonate-mutagenized pea seedlings for
      FR-unresponsive, potentially phyA-deficient mutants. Two allelic, recessive
      mutants were isolated and were designated fun1 for FR unresponsive. The fun1-1
      mutant is specifically deficient in the PHYA apoprotein and has a seedling
      phenotype indistinguishable from wild type when grown under white light. However,
      fun1-1 plants grown to maturity under long photoperiods show a highly pleiotropic
      phenotype, with short internodes, thickened stems, delayed flowering and
      senescence, longer peduncles, and higher seed yield. This phenotype results in
      large part from an inability of fun1-1 to detect day extensions. These results
      establish a crucial role for phyA in the control of flowering in pea, and show
      that phyA mediates responses to both red and FR light. Furthermore, grafting and
      epistasis studies with fun1 and dne, a mutant deficient in the floral inhibitor,
      show that the roles of phyA in seedling deetiolation and in day-length detection
      are genetically separable and that the phyA-mediated promotion of flowering
      results from a reduction in the synthesis or transport of the floral inhibitor.

PMID- 12223769
TI  - The Ascorbate Carrier of Higher Plant Plasma Membranes Preferentially
      Translocates the Fully Oxidized (Dehydroascorbate) Molecule.
AB  - Recently, the uptake of 14C-labeled ascorbate (ASC) into highly purified bean
      (Phaseolus vulgaris L.) plasma membrane vesicles was demonstrated in our
      laboratory. However, the question of the redox status of the transported molecule
      (ASC or dehydroascorbate [DHA]) remained unanswered. In this paper we present
      evidence that DHA is transported through the plasma membrane. High-performance
      liquid chromatography analysis of the redox status of ASC demonstrated that
      freshly purified plasma membranes exhibit a high ASC oxidation activity. Although
      it is not yet clear whether this activity is enzymatic, it complicates the
      interpretation of ASC-transport experiments in vitro and in vivo. In an attempt
      to correlate the ASC redox status to transport of the molecule, the ability of
      different compounds to reduce DHA was analyzed and their effect on ASC-transport
      activity tested. Administering of various reductants resulted in different levels
      of inhibition of ASC uptake (dithiothreitol > dithioerythritol > [beta]
      mercaptoethanol > [beta]-mercaptopropanol). Glutathione, cysteine, dithionite,
      and thiourea did not significantly affect ASC transport. Statistical analysis
      indicated a strong correlation of the Spearman rank correlation coefficient (Rs)
      of 0.919 (P = 0.0005, n = 9) between the level of ASC oxidation and the amount of
      transported molecules into the vesicles. The administering of ASC oxidants such
      as ferricyanide and ASC oxidase resulted in a stimulated ASC uptake into the
      plasma membrane vesicles. Together, our results demonstrate that a vitamin C
      carrier in purified bean plasma membranes translocates DHA from the apoplast to
      the cytosol.

PMID- 12223770
TI  - Inorganic Carbon Accumulation Stimulates Linear Electron Flow to Artificial
      Electron Acceptors of Photosystem I in Air-Grown Cells of the Cyanobacterium
      Synechococcus UTEX 625.
AB  - The effect of inorganic carbon (Ci) transport and accumulation on photosynthetic
      electron transport was studied in air-grown cells of the cyanobacterium
      Synechococcus UTEX 625. When the cells were depleted of Ci, linear photosynthetic
      electron flow was almost completely inhibited in the presence of the photosystem
      I (PSI) acceptor N,N-dimethyl-p-nitrosoaniline (PNDA). The addition of Ci to
      these cells, in which CO2 fixation was inhibited with glycolaldehyde, greatly
      stimulated linear electron flow and resulted in increased levels of photochemical
      quenching and O2 evolution. In aerobic conditions substantial quenching resulted
      from methyl viologen (MV) addition and further quenching was not observed upon
      the addition of Ci. In anaerobic conditions MV addition did not result in
      quenching until Ci was added. Intracellular Ci pools were formed when MV was
      present in aerobic or anaerobic conditions or PNDA was present in aerobic
      conditions. There was no inhibitory effect of Ci depletion on electron flow to
      2,6-dimethylbenzoquinone and oxidized diaminodurene, which accept electrons from
      photosystem II. The degree of stimulation of PNDA-dependent O2 evolution varied
      with the Ci concentration. The extracellular Ci, concentration required for a
      half-maximum rate (K1/2) was 3.8 [mu]M and the intracellular K1/2 was 1.4 mM for
      the stimulation of PNDA reduction. These values agreed closely with the K1/2
      values of extracellular and intracellular Ci for O2 photoreduction. Linear
      electron flow to artificial electron acceptors of PSI was enhanced by
      intracellular Ci, which appeared to exert an effect on PSI or on the intersystem
      electron transport chain.

PMID- 12223771
TI  - Involvement of Cytochrome P450 in Glucosinolate Biosynthesis in White Mustard (A
      Biochemical Anomaly).
AB  - One of the first steps in glucosinolate biosynthesis is the conversion of amino
      acids to their aldoximes. The biochemistry of this process is controversial, and
      several very different enzyme systems have been described. The major
      glucosinolate in white mustard (Sinapis alba) is sinalbin, which is derived from
      tyrosine via its aldoxime, and this conversion is catalyzed by a cytochrome P450
      (Cyt P450) monooxygenase. Phenylethyl- and alkenylglucosinolates are also present
      in white mustard leaves, as are the enzymes catalyzing the relevant aldoxime
      formation from homophenylalanine and methionine homologs, respectively. These
      enzymes are similar to those found in Brassica sp. and are distinct from the
      tyrosine-dependent enzyme in that they contain no heme and are unaffected by Cyt
      P450 inhibitors. They are instead inhibited by the flavoprotein inhibitor
      diphenylene iodonium and by Cu2+. In both white mustard and oilseed rape
      (Brassica napus) methyl jasmonate specifically stimulates indolylglucosinolate
      biosynthesis and yet has no effect on sinalbin accumulation in either cotyledons
      or leaves of white mustard. White mustard appears to be unique among crucifers in
      having a Cyt P450 aldoxime-forming enzyme for biosynthesis of one glucosinolate,
      although it also contains all of the non-Cyt P450 enzyme systems found in other
      members of the family. Sinalbin biosynthesis in white mustard is therefore an
      inappropriate model system for the synthesis of other glucosinolates in
      crucifers, including canola and oilseed rape.

PMID- 12223772
TI  - Leaf-Atmosphere NH3 Exchange in Barley Mutants with Reduced Activities of
      Glutamine Synthetase.
AB  - Mutants of barley (Hordeum vulgare L. cv Maris Mink) with 47 or 66% of the
      glutamine synthetase (GS) activity of the wild type were used for studies of NH3
      exchange with the atmosphere. Under normal light and temperature conditions,
      tissue NH4+ concentrations were higher in the two mutants compared with wild-type
      plants, and this was accompanied by higher NH3 emission from the leaves. The
      emission of NH3 increased with increasing leaf temperatures in both wild-type and
      mutant plants, but the increase was much more pronounced in the mutants. Similar
      results were found when the light intensity (photosynthetic photon flux density)
      was increased. Compensation points for NH3 were estimated by exposing intact
      shoots to 10 nmol NH3 mol-1 air under conditions with increasing temperatures
      until the plants started to emit NH3. Referenced to 25[deg]C, the compensation
      points were 5.0 nmol mol-1 for wild-type plants, 8.3 nmol mol-1 for 47% GS
      mutants, and 11.8 nmol mol-1 for 66% GS mutants. Compensation points for NH3 in
      single, nonsenescent leaves were estimated on the basis of apoplastic pH and NH4+
      concentrations. These values were 0.75, 3.46, and 7.72 nmol mol-1 for wild type,
      47% GS mutants, and 66% GS mutants, respectively. The 66% GS mutant always showed
      higher tissue NH4+ concentrations, NH3 emission rates, and NH3 compensation
      points compared with the 47% GS mutant, indicating that NH4+ release was
      curtailed by some kind of compensatory mechanism in plants with only 47% GS
      activity.

PMID- 12223773
TI  - The Effect of Cu2+ on Ion Transport Systems of the Plant Cell Plasmalemma.
AB  - Changes in plasmalemma permeability caused by excessive Cu2+ levels were examined
      in cells of a freshwater alga (Nitella flexilis) using a conventional
      microelectrode voltage-clamp technique. A rapid Cu2+-induced increase of
      plasmalemma conductance starting from 5 [mu]M Cu2+ was shown. Cu2+-induced
      plasmalemma conductance (ClGm) was nonselective and potential-independent,
      resembling the conductance of nonselective ionic leakage of the plasmalemma. The
      K+ channel conductance was shown to be unaltered by Cu2+, and a decrease in
      plasmalemma Cl- channel conductance at Cu2+ concentrations above 5 [mu]M was
      found. The depression of Cl- channels and ClGm were time-, dosage-, and Ca2+
      dependent processes, revealing a great similarity in all parameters, with Ca2+
      causing the preventive effect by shifting the effective Cu2+ concentrations to
      higher levels. This phenomenon may be explained by the same Cu2+-modified target
      on the plasmalemma both for ClGm and Cl- channel depression. In addition, a
      reversible, inhibitory effect of Cu2+ (>10 [mu]M) on the light-stimulated H+
      ATPase electrogenic pump in the plasmalemma was demonstrated. This effect was
      Ca2+- independent, which made it possible to distinguish it from ClGm. Therefore,
      the Cu2+-induced dramatic alterations in plant cell plasmalemma permeability are
      caused mainly by nonselective conductance increases and electrogenic pump
      inhibition.

PMID- 12223775
TI  - Role of Catalase in Inducing Chilling Tolerance in Pre-Emergent Maize Seedlings.
AB  - The mechanisms of chilling acclimation and the role of antioxidant enzymes,
      catalase in particular, in inducing chilling tolerance in pre-emergent maize (Zea
      mays L.) seedlings have been investigated. Seedlings were acclimated to chilling
      stress in two different ways. Three-day-old seedlings did not survive 7 d of
      4[deg]C stress unless acclimated by exposure to either 14[deg]C for 1 d or
      4[deg]C for 1 d followed by recovery at 27[deg]C for 1 d. Although no changes in
      superoxide dismutase and ascorbate peroxidase activities were observed, both
      kinds of acclimated seedlings had higher catalase (CAT), glutathione reductase,
      and guaiacol peroxidase activities compared with nonacclimated seedlings during
      low-temperature stress and recovery conditions. To study the role of CAT in
      chilling tolerance, aminotriazole (AT) was used as a tool to artificially inhibit
      CAT activity and to initiate oxidative stress in the seedlings. Treatment of
      acclimating seedlings with 3 mM AT for 18 h abolished the acclimation phenomenon.
      AT treatment was found to be specific to CAT inhibition, because the total
      activities or isozyme profiles of the other investigated antioxidant enzymes were
      not altered in AT-treated seedlings. Protein carbonyl content, an indication of
      oxidative damage, was increased 2-fold in nonacclimated and AT-treated acclimated
      seedlings. These results collectively indicate that acclimation to prolonged
      chilling stress can be achieved by briefly pre-exposing the seedlings to 4[deg]C
      chilling stress and that acclimation-induced (oxidative stress-induced) CAT seems
      to play a major role, probably along with other antioxidant enzymes, in inducing
      chilling tolerance in pre-emergent maize seedlings.

PMID- 12223774
TI  - The Formation of Nitrogen-Fixing Bacteroids Is Delayed but Not Abolished in
      Soybean Infected by an [alpha]-Ketoglutarate Dehydrogenase-Deficient Mutant of
      Bradyrhizobium japonicum.
AB  - A mutant strain of Bradyrhizobium japonicum USDA 110 devoid of [alpha]
      ketoglutarate dehydrogenase activity (LSG184) was used to test whether this
      tricarboxylic acid cycle enzyme is necessary to support nitrogen fixation during
      symbiosis with soybean (Glycine max). LSG184 formed nodules about 5 d later than
      the wild-type strain, and the nodules, although otherwise normal in structure,
      contained many fewer infected host cells than is typical. At 19 d after
      inoculation cells infected with the mutant strain were only partially filled with
      bacteroids and showed large accumulations of starch, but by 32 d after
      inoculation the host cells infected with the mutant appeared normal. The onset of
      nitrogen fixation was delayed about 15 d for plants inoculated with LSG184, and
      the rate, on a per nodule fresh weight basis, reached only about 20% of normal.
      However, because nodules formed by LSG184 contained only about 20% of the normal
      number of bacteroids, it could be inferred that the mutant, on an individual
      bacteroid basis, was fixing nitrogen at near wild-type rates. Therefore, the loss
      of [alpha]-ketoglutarate dehydrogenase in B. japonicum does not prevent the
      formation or the functioning of nitrogen-fixing bacteroids in soybean.

PMID- 12223776
TI  - Characterization of Nitrate Reductase from Light- and Dark-Exposed Leaves
      (Comparison of Different Species and Effects of 14-3-3 Inhibitor Proteins).
AB  - Nitrate reductase (NR) was extracted and partially purified from leaves of squash
      (Curcurbita maxima), spinach (Spinacia oleracea), and three transgenic Nicotiana
      plumbaginifolia leaves in the presence of phosphatase inhibitors to preserve its
      phosphorylation state. Purified squash NR showed activation by substrates
      (hysteresis) when prepared from leaves in the light as well as in darkness. A 14
      3-3 protein known to inhibit phosphorylated spinach NR in the presence of Mg2+
      decreased by 70 to 85% the activity of purified NR from dark-exposed leaves,
      whereas NR from light-exposed leaves decreased by 10 to 25%. Apparent lack of
      posttranslational NR regulation in a transgenic N. plumbaginifolia expressing an
      NR construct with an N-terminal deletion ([delta]NR) may be explained by more
      easy dissociation of 14-3-3 proteins from [delta]NR. Partially purified [delta]NR
      was, however, inhibited by 14-3-3 protein, and the binding constant of 14-3-3
      protein (4 x 108 M-1) and the NR-inhibiting protein concentration that results in
      a 50% reduction of free NR (2.5 nM) were the same for NR and [delta]NR.
      Regulation of NR activity by phosphorylation and binding of 14-3-3 protein was a
      general feature for all plants tested, whereas activation by substrates as a
      possible regulation mechanism was verified only for squash.

PMID- 12223777
TI  - Temperature-Sensitive Plant Cells with Shunted Indole-3-Acetic Acid Conjugation.
AB  - Cells of henbane (Hyoscyamus muticus L.) grow indefinitely in culture without
      exogenous auxin. Cells of its temperature-sensitive variant XIIB2 grow like the
      wild type at 26[deg]C but die rapidly at 33[deg]C unless auxin is added to the
      medium. Despite this temperature-sensitive auxin auxotrophy, XIIB2 produces wild
      type amounts of indole-3-acetic acid (IAA). IAA is the predominant auxin and is
      important for plant growth and development. Since the IAA production of the
      variant is functional, we investigated whether the synthesis or degradation of
      IAA metabolites, possibly active auxins themselves, is altered. The IAA
      metabolites were IAA-aspartate (IAAsp) and IAA-glucose. The wild type converted
      IAA mainly to IAAsp, whereas the variant produced mainly IAA-glucose. Exogenous
      auxin corrected the shunted IAA metabolism of the variant. The half-life of
      labeled IAAsp in the variant was reduced 21-fold, but in the presence of
      exogenous auxin it was not different from the wild type. The temperature
      sensitivity of XIIB2 was also corrected by supplying IAAsp. Pulse-chase
      experiments revealed that henbane rapidly metabolizes IAAsp to compounds not
      identical to IAA. The data show that the variant XIIB2 is a useful tool to study
      the function of IAA conjugates to challenge the popular hypothesis that IAA
      conjugates are merely slow-release storage forms of IAA.

PMID- 12223778
TI  - Phosphoryl Group Exchange between ATP and ADP Catalyzed by H+-ATPase from Oat
      Roots.
AB  - ATP-ADP exchange was estimated in the presence of plasma membrane H+-ATPase of
      oat (Avena sativa) roots partially purified with Triton X-100 by measuring
      [14C]ATP formation from [14C]ADP. Most studies were done at 0[deg]C. At pH 6.0
      the exchange showed: (a) Mg2+ requirement with a biphasic response giving maximal
      activity at 152 [mu]M and (b) insensitivity to ionic strength, [Na+], and [K+].
      ATP and ADP dependence were analyzed with a model in which nucleotide-enzyme
      interactions are at rapid-random equilibrium, whereas E1ATP [left right arrow]
      E1P-ADP transitions occur in steady state. The results indicated competition
      between ADP and ATP for the catalytic site, whereas ATP interaction with the ADP
      site was extremely weak. At 0[deg]C the exchange showed a 3-fold pH increase,
      from pH 5.5 to 9.0. At an alkaline pH the reaction was not affected by sodium
      azide and carbonyl cyanide p-trifluometoxyphenyl-hydrazone, had a biphasic
      response to Mg2+ (maximal at 513 [mu]m), and was insensitive to ionic strength.
      At 20[deg]C ATP-ADP exchange was pH insensitive. At both temperatures ATP
      hydrolysis displayed a bell-shaped response, with a maximum around pH 6.0 to 6.5.
      Because no adenylate kinase activity was detected under any condition, these
      results demonstrate the existence of an ATP-ADP exchange reaction catalyzed by
      the plant H+-ATPase.

PMID- 12223779
TI  - Nitrogenase Activity Is Affected by Reduced Partial Pressures of N2 and NO3- 1.
AB  - Optimal use of legumes in cropping systems requires a thorough understanding of
      the interaction between inorganic N nutrition and symbiotic N2 fixation. Our
      objective was to test the hypothesis that increased NO3- uptake by alfalfa
      (Medicago sativa L.) would compensate for lower N2 fixation caused by low partial
      pressure of N2. Root systems of hydroponically grown alfalfa at 2 mg L-1 NO3--N
      were exposed to (a) 80% N2, (b) 7% N2, (c) 2% N2, or (d) 0% N2. Exposure to
      reduced partial pressures of N2 reduced total nitrogenase activity (TNA, measured
      as H2 production in 20% O2 and 80% Ar) by 40% within less than 30 min, followed
      by a recovery period over the next 30 min to initial activity. Five hours after
      treatments began, the TNA of plants exposed to 7 and 2% N2 was substantially
      higher than pretreatment activities, whereas the TNA of plants exposed either to
      0 or 80% N2 did not differ from pretreatment values. The decline in TNA due to
      NO3- exposure over 4 d was not affected by reduced partial pressure of N2. During
      the 1st h the proportion of electrons used for the reduction of N2 fell from 0.52
      to 0.23 for plants exposed to 7% N2, and to 0.09 for plants exposed to 2% N2, and
      remained unchanged for the rest of the experiment. Although the hypothesis that
      alfalfa compensated with increased NO3- uptake for lower N2 fixation was not
      validated by our results, we unexpectedly demonstrated that the decline in TNA
      upon exposure to NO3- was independent of the N2-fixing efficiency (i.e. the
      amount of N2 reduced by nitrogenase) of the symbiosis.

PMID- 12223780
TI  - In Vivo and in Vitro Studies of Glucose-6-Phosphate Dehydrogenase from Barley
      Root Plastids in Relation to Reductant Supply for NO2- Assimilation.
AB  - Pyridine nucleotide pools were measured in intact plastids from roots of barley
      (Hordeum vulgare L.) during the onset of NO2- assimilation and compared with the
      in vitro effect of the NADPH/NADP ratio on the activity of plastidic glucose-6
      phosphate dehydrogenase (G6PDH, EC 1.1.1.49) from N-sufficient or N-starved
      roots. The NADPH/NADP ratio increased from 0.9 to 2.0 when 10 mM glucose-6
      phosphate was supplied to intact plastids. The subsequent addition of 1 mM NaNO2
      caused a rapid decline in this ratio to 1.5. In vitro, a ratio of 1.5 inactivated
      barley root plastid G6PDH by approximately 50%, suggesting that G6PDH could
      remain active during NO2- assimilation even at the high NADPH/NADP ratios that
      would favor a reduction of ferredoxin, the electron donor of NO2- reductase. Root
      plastid G6PDH was sensitive to reductive inhibition by dithiothreitol (DTT), but
      even at 50 mM DTT the enzyme remained more than 35% active. In root plastids from
      barley starved of N for 3 d, G6PDH had a substantially reduced specific activity,
      had a lower Km for NADP, and was less inhibited by DTT than the enzyme from N
      sufficient root plastids, indicating that there was some effect of N starvation
      on the G6PDH activity in barley root plastids.

PMID- 12223781
TI  - Enrichment in Specific Soluble Sugars of Two Eucalyptus Cell-Suspension Cultures
      by Various Treatments Enhances Their Frost Tolerance via a Noncolligative
      Mechanism.
AB  - A cell-suspension culture obtained from the hybrid Eucalyptus gunnii/Eucalyptus
      globulus was hardened by exposure to lower temperatures, whereas in the same
      conditions cells from a hybrid with a more frost-sensitive genotype, Eucalyptus
      cypellocarpa/Eucalyptus globulus, were not able to acclimate. During the cold
      exposure the resistant cells accumulated soluble sugars, in particular fructose
      and sucrose, with a limited increase in cell osmolality. In contrast, the cell
      suspension that was unable to acclimate did not accumulate soluble sugars in
      response to the same cold treatment. To an extent similar to that induced after a
      cold acclimation, frost-hardiness of the cells increased after a 14-h incubation
      with specific soluble sugars such as sucrose, raffinose, fructose, and mannitol.
      Such hardening was also observed for long-term cultures in mannitol-enriched
      medium. This cryoprotective effect of sugars without exposure to lower
      temperatures was observed in both the resistant and the sensitive genotypes.
      Mannitol was one of the most efficient carbohydrates for the cryoprotection of
      eucalyptus. The best hardiness (a 2.7-fold increase in relative freezing
      tolerance) was obtained for the resistant cells by the cumulative effect of cold
      induced acclimation and mannitol treatment. This positive effect of certain
      sugars on eucalyptus freezing tolerance was not colligative, since it was
      independent of osmolality and total sugar content.

PMID- 12223782
TI  - Local and Systemic Responses of Antioxidants to Tobacco Mosaic Virus Infection
      and to Salicylic Acid in Tobacco (Role in Systemic Acquired Resistance).
AB  - Changes in ascorbate and glutathione levels and in activities of ascorbate
      peroxidase, catalase, dehydroascorbate reductase (DHAR), glutathione reductase
      (GR), glutathione S-transferase (GST), and superoxide dismutase (SOD) were
      investigated in tobacco mosaic virus (TMV)-inoculated lower leaves and in non
      inoculated upper leaves of Nicotiana tabacum L. cv Xanthi-nc. In separate
      experiments the effects of exogenous salicylic acid (SA) were also studied.
      Symptom appearance after TMV inoculation was preceded by a slight, transient
      decline of ascorbate peroxidase, GR, GST, and SOD activities in the inoculated
      lower leaves, but after the onset of necrosis these activities and the
      glutathione level substantially increased. Ascorbic acid level and DHAR activity
      declined and dehydroascorbate accumulated in the inoculated leaves. In upper
      leaves, the glutathione level and the activities of GR, GST, and SOD increased 10
      to 14 d after TMV inoculation of the lower leaves, concomitantly with the
      development of systemic acquired resistance. From the six distinct SOD isoenzymes
      found in tobacco leaves, only the activities of Cu,Zn-SOD isoenzymes were
      affected by TMV. SA injection induced DHAR, GR, GST, and SOD activities. Catalase
      activities were not modified by TMV infection or SA treatment. It is supposed
      that stimulated antioxidative processes contribute to the suppression of necrotic
      symptom development in leaves with systemic acquired resistance.

PMID- 12223783
TI  - Effect of Cold Acclimation on the Lipid Composition of the Inner and Outer
      Membrane of the Chloroplast Envelope Isolated from Rye Leaves.
AB  - The lipid composition of the inner and outer membranes of the chloroplast
      envelope isolated from winter rye (Secale cereale L. cv Puma) leaves was
      characterized before and after cold acclimation. In nonacclimated leaves the
      inner membrane contained high proportions of monogalactosyldiacylglycerols (MGDG,
      47.9 mol% of the total lipids) and digalactosyldiacylglycerols (DGDG, 31.1 mol%)
      and a low proportion of phosphatidylcholine (PC, 8.1 mol%). The outer membrane
      contained a similar proportion of DGDG (30.0 mol%); however, the proportion of
      MGDG was much lower (20.1 mol%) and the proportion of PC was much higher (31.5
      mol%). After 4 weeks of cold acclimation, the proportions of these lipid classes
      were significantly altered in both of the inner and outer membranes. In the inner
      membrane the proportion of MGDG decreased (from 47.9 to 38.4 mol%) and the
      proportion of DGDG increased (from 31.1 to 39.3 mol%), with only a slight change
      in the proportion of PC (from 8.1 to 8.8 mol%). In the outer membrane MGDG
      decreased from 20.1 to 14.8 mol%, DGDG increased from 30.0 to 39.9 mol%, and PC
      decreased from 31.5 to 25.4 mol%. Thus, both before and after cold acclimation,
      the proportion of MGDG was much higher in the inner membrane than in the outer
      membrane. In contrast, the proportion of PC was higher in the outer membrane than
      in the inner membrane. The relationship between the lipid composition of the
      inner and outer membranes of the chloroplast envelope and freeze-induced membrane
      lesions is discussed.

PMID- 12223784
TI  - Ethylene Sensitivity and Response Sensor Expression in Petioles of Rumex Species
      at Low O2 and High CO2 Concentrations.
AB  - Rumex palustris, a flooding-tolerant plant, elongates its petioles in response to
      complete submergence. This response can be partly mimicked by enhanced ethylene
      levels and low O2 concentrations. High levels of CO2 do not markedly affect
      petiole elongation in R. palustris. Experiments with ethylene synthesis and
      action inhibitors demonstrate that treatment with low O2 concentrations enhances
      petiole extension by shifting sensitivity to ethylene without changing the rate
      of ethylene production. The expression level of the R. palustris gene coding for
      the putative ethylene receptor (RP-ERS1) is up-regulated by 3% O2 and increases
      after 20 min of exposure to a low concentration of O2, thus preceding the first
      significant increase in elongation observable after 40 to 50 min. In the flooding
      sensitive species Rumex acetosa, submergence results in a different response
      pattern: petiole growth of the submerged plants is the same as for control
      plants. Exposure of R. acetosa to enhanced ethylene levels strongly inhibits
      petiole growth. This inhibitory effect of ethylene on R. acetosa can be reduced
      by both low levels of O2 and/or high concentrations of CO2.

PMID- 12223786
TI  - The Electronic Plant Gene Register.

PMID- 12223785
TI  - Cell Wall Metabolism in Ripening Fruit (IX. Synthesis of Pectic and
      Hemicellulosic Cell Wall Polymers in the Outer Pericarp of Mature Green Tomatoes
      (cv XMT-22).
AB  - Discs of outer pericarp were excised from mature green tomato (Lycopersicon
      esculentum Mill.) fruit and kept in sterile tissue culture plates for 4 d,
      including 2 d of incubation with D-[U-13C]glucose. Cell walls were prepared and
      the water-soluble, pectic, and hemicellulosic polymers were extracted. Cell wall
      synthetic capacity was determined by gas chromatography-mass spectrometry
      analysis of incorporation of the heavy isotope label. The "outer" 2-mm pericarp
      region, which included the cuticle, had a lower cell wall synthetic capacity than
      the "inner" 2-mm region immediately below it (closer to the locules), based on
      the percentage of labeling of the neutral sugars. There were no significant
      differences in relative abundance of glycosidic linkages in the two tissue
      regions. Label was incorporated into neutral sugars and linkages typical for each
      polysaccharide class were identified in the cell wall preparations. Galacturonic
      acid and glucuronic acid were labeled to an extent similar to that of the neutral
      sugars in each tissue region.

PMID- 12223787
TI  - The Metabolism and Functions of [gamma]-Aminobutyric Acid.

PMID- 12223788
TI  - Sugar Sensing and Sugar-Mediated Signal Transduction in Plants.

PMID- 12223789
TI  - Accelerated Early Growth of Rice at Elevated CO2 (Is It Related to Developmental
      Changes in the Shoot Apex?).
AB  - The influence of elevated CO2 on the development of the shoot apex and on
      subsequent vegetative growth and grain yield was investigated using rice (Oryza
      sativa L. cv Jarrah) grown in flooded soil at either 350 or 700 [mu]L CO2 L-1. At
      8 d after planting (DAP), elevated CO2 increased the height and diameter of the
      apical dome and lengths of leaf primordia and tiller buds but had no effect on
      their numbers. By 16 DAP, there were five tiller buds in the apex at 700 [mu]L
      CO2 L-1 compared with only three tiller buds at 350 [mu]L CO2 L-1. These changes
      in development of the shoot apex at high CO2 were forerunners to faster
      development of the vegetative shoot at elevated CO2 between 11 and 26 DAP as
      evidenced by increases in the relative growth rates of the shoot and tillers.
      Accelerated development at high CO2 was responsible for the 42% increase in
      tiller number at the maximum tillering stage and the 57% enhancement of grain
      yield at the final harvest. The link between high CO2 effects on development
      during the first 15 DAP and final tiller number and grain yield was demonstrated
      by delaying exposure of plants to high CO2 for 15 d. The delay totally inhibited
      the tillering response to high CO2, and the increase in grain yield of 20% arose
      from a greater number of grains per panicle. Consequently, it can be concluded
      that accelerated development in the shoot apex early in development is crucial
      for obtaining maximum increases in grain yield at elevated atmospheric CO2
      concentrations.

PMID- 12223790
TI  - Reduced Lignin Content and Altered Lignin Composition in Transgenic Tobacco Down
      Regulated in Expression of L-Phenylalanine Ammonia-Lyase or Cinnamate 4
      Hydroxylase.
AB  - We analyzed lignin content and composition in transgenic tobacco (Nicotiana
      tabacum) lines altered in the expression of the early phenylpropanoid
      biosynthetic enzymes L-phenylalanine ammonia-lyase and cinnamate 4-hydroxylase
      (C4H). The reduction of C4H activity by antisense expression or sense suppression
      resulted in reduced levels of Klason lignin, accompanied by a decreased
      syringyl/guaiacyl monomer ratio as determined by pyrolysis gas
      chromatography/mass spectrometry Similar reduction of lignin levels by down 
      regulation of L-phenylalanine ammonia-lyase, the enzyme preceding C4H in the
      central phenylpropanoid pathway, did not result in a decreased syringyl/guaiacyl
      ratio. Rather, analysis of lignin methoxyl content and pyrolysis suggested an
      increased syringyl/guaiacyl ratio. One possible explanation of these results is
      that monolignol biosynthesis from L-phenylalanine might occur by more than one
      route, even at the early stages of the core phenylpropanoid pathway, prior to the
      formation of specific monolignol precursors.

PMID- 12223791
TI  - Increases in Cytosolic Ca2+ in Parsley Mesophyll Cells Correlate with Leaf
      Senescence.
AB  - The ability to maintain the cytoplasmic Ca2+ concentration ([Ca2+]cyt) at
      homeostatic levels has been examined during leaf senescence in detached parsley
      (Petroselinum crispum) leaves. Fluorescence ratiometric imaging of mesophyll
      cells isolated from parsley leaves at various senescence stages and loaded with
      the Ca2+ indicator fura-2 has revealed a distinct elevation of [Ca2+]cyt, which
      was positively correlated with the progress of leaf senescence. This initial
      increase of [Ca2+]cyt, which was first observed in cells isolated from 3-d
      senescent leaves, occurred 1 d before or in parallel with changes in two
      established senescence parameters, chlorophyll loss and lipid peroxidation.
      However, the [Ca2+]cyt elevation followed by 2 d the initial increase in the
      senescence-associated proteolysis. Whereas the [Ca2+]cyt of nonsenescent cells
      remained at the basal level, the elevated [Ca2+]cyt of the senescent cells was a
      long-lasting effect. Experimental retardation of senescence processes, achieved
      by pretreatment of detached leaves with the cytokinin benzyladenine, resulted in
      maintenance of homeostatic levels of [Ca2+]cyt in cells isolated from 3-d
      senescent leaves. These observations demonstrate for the first time to our
      knowledge a correlation between elevated [Ca2+]cyt and the process of senescence
      in parsley leaves. Such senescence-associated elevation of [Ca2+]cyt, which
      presumably results from a loss of the cell's capability to extrude Ca2+, may
      serve as a signal inducing subsequent deteriorative processes.

PMID- 12223792
TI  - Gene-Expression Patterns and Levels of Jasmonic Acid in Rice Treated with the
      Resistance Inducer 2,6-Dichloroisonicotinic Acid.
AB  - Acquired disease resistance can be induced in rice (Oryza sativa) by a number of
      synthetic or natural compounds, but the molecular mechanisms behind the
      phenomenon are poorly understood. One of the synthetic inducers of resistance,
      2,6-dichloroisonicotinic acid (INA), efficiently protected rice leaves from
      infection by the rice blast fungus Magnaporthe grisea (Hebert) Barr. A comparison
      of gene-expression patterns in plants treated with INA versus plants inoculated
      with the compatible pathogen M. grisea or the incompatible pathogen Pseudomonas
      syringae pv syringae revealed only a marginal overlap: 6 gene products, including
      pathogenesis-related proteins (PR1-PR9), accumulated in both INA-treated and
      pathogen-attacked leaves, whereas 26 other gene products accumulated only in INA
      treated or only in pathogen-attacked leaves. Lipoxygenase enzyme activity and
      levels of nonconjugated jasmonic acid (JA) were enhanced in leaves of plants
      treated with a high dose of INA (100 ppm). Exogenously applied JA enhanced the
      gene induction and plant protection caused by lower doses of INA (0.1 to 10 ppm)
      that by themselves did not give rise to enhanced levels of endogenous (-)-JA.
      These data suggest that INA, aside from activating a pathogen-induced signaling
      pathway, also induces events that are not related to pathogenesis. JA acts as an
      enhancer of both types of INA-induced reactions in rice.

PMID- 12223793
TI  - Formation of Di-Isodityrosine and Loss of Isodityrosine in the Cell Walls of
      Tomato Cell-Suspension Cultures Treated with Fungal Elicitors or H2O2.
AB  - About 84% of the hydroxyproline residues in a cell culture of tomato
      (Lycopersicon esculentum x Lycopersicon peruvianum) were present in phenol
      inextractable (i.e. covalently wall-bound) material. Treatment of the cells with
      any of three fungal elicitors (wall fragments from Phytophthora megasperma and
      Pythium aphanidermatum and xylanase from Aureobasidium pullulans) or with 1 mM
      H2O2 had little effect on the quantity of phenolinextractable hydroxyproline per
      milligram of freeze-dried cells. However, each treatment induced a decrease in
      the content of phenol-inextractable isodityrosine (Idt) residues. Each treatment,
      except with the P. megasperma fragments, also induced an increase in phenol
      inextractable di- (Di-Idt). The increase in Di-Idt partly accounted for the loss
      of Idt. We conclude that the elicitors and H2O2 acted to reinforce the existing
      cross-linking of cell wall (glyco)proteins by evoking oxidative coupling
      reactions to convert Idt to Di-Idt plus unidentified products. The promotion of
      cross-linking by elicitor treatment is proposed to be a defensive response that
      restricts the penetration of pathogens.

PMID- 12223794
TI  - Regulation of Growth Anisotropy in Well-Watered and Water-Stressed Maize Roots
      (I. Spatial Distribution of Longitudinal, Radial, and Tangential Expansion
      Rates).
AB  - As a system to study the regulation of growth anisotropy, we studied thinning of
      the primary root of maize (Zea mays L.) occurring developmentally or induced by
      water stress. Seedlings were transplanted into vermiculite at a water potential
      of approximately -0.03 MPa (well-watered) or -1.6 MPa (water-stressed). The
      diameter of roots in both treatments decreased with time after transplanting; the
      water-stressed roots became substantially thinner than well-watered roots at
      steady state, showing that root thinning is a genuine response to water stress.
      To analyze the thinning responses we quantified cell numbers and the spatial
      profiles of longitudinal, radial, and tangential expansion rates separately for
      the cortex and stele. The results showed that there was no zone of isotropic
      expansion and the degree of anisotropy varied greatly with position and
      treatment. Thinning over time in well-watered roots was caused by rates of radial
      and tangential expansion being too low to maintain the shape of the root. In
      response to low water potential, cell number in both tissues was unchanged
      radially but increased tangentially, which shows that thinning was caused wholly
      by reduced cell expansion. Water stress substantially decreased rates of
      tangential and radial expansion in both the stele and cortex, but only in the
      apical 5 mm of the root; basal to this, rates were similar in well-watered and
      water-stressed roots. By contrast, as in previous studies, longitudinal expansion
      was identical between the treatments in the apical 3 mm but in water-stressed
      roots was inhibited at more basal locations. The results show that expansion in
      longitudinal and radial directions can be regulated independently.

PMID- 12223795
TI  - Seed and Hormonal Regulation of Gibberellin 20-Oxidase Expression in Pea
      Pericarp.
AB  - To understand further how seeds, auxin (4-chloroindole-3-acetic acid [4-Cl-IAA]),
      and gibberellins (GAs) regulate GA biosynthesis in pea (Pisum sativum L.)
      pericarp at the molecular level, we studied the expression of GA 20-oxidase in
      this tissue using northern-blot analysis. Pericarp GA 20-oxidase mRNA levels were
      highest from prepollination (-2 d after anthesis [DAA]) through anthesis (0 DAA),
      then decreased 3-fold by 2 DAA, and remained at these levels through 6 DAA. The
      effects of seeds and hormones (4-Cl-IAA and GA3) on the expression of GA 20
      oxidase in pea pericarp were investigated over a 36-h treatment period. GA 20
      oxidase mRNA levels in 2 DAA pericarp with seeds remained relatively stable
      throughout the treatment period; however, when the seeds were removed the
      pericarp transcript levels declined. When 2 DAA deseeded pericarps were treated
      with 4-Cl-IAA, a significant increase in GA 20-oxidase mRNA levels was detected
      within 2 h and transcript levels remained elevated for up to 12 h after 4-Cl-IAA
      application. GA3 significantly decreased GA 20-oxidase mRNA levels in deseeded
      pericarp within 2 h of application. These data suggest that the previously
      reported conversion of GA19 to GA20 in pea pericarp is controlled by seeds, 4-Cl
      IAA, and GA3 at least in part by regulating GA 20-oxidase mRNA levels in this
      tissue.

PMID- 12223796
TI  - Antenna Size Dependency of Photoinactivation of Photosystem II in Light
      Acclimated Pea Leaves.
AB  - Utilization of absorbed light energy by photosystem (PS) II for O2 evolution
      depends on the light-harvesting antenna size, but the role of antenna size in the
      photoinactivation of PSII seems controversial. To address this controversy, pea
      (Pisum sativum L.) plants were grown in low (50 [mu]mol m-2 s-1) or high (650
      [mu]mol m-2 s-1) light. The doubled functional antenna size of PSII in low light
      allows each PSII to utilize twice as many photons at given flash light energies
      for O2 evolution. The application of a target theory to depict the photon dose
      dependency of PSII photoinactivation measured by repetitive-flash O2 yield and
      the ratio of variable to maximal chlorophyll fluorescence indicates that
      photoinactivation of PSII is probably a single-hit process in which repair or
      photoprotective mechanisms are only slightly involved. Furthermore, the
      exacerbation of photoinactivation of PSII with greater antenna size under
      anaerobic conditions strongly indicates that photoinactivation of PSII depends on
      antenna size.

PMID- 12223797
TI  - Effects of Osmoprotectants upon NaCl Stress in Rice.
AB  - Plants accumulate a number of osmoprotective substances in response to NaCl
      stress, one of them being proline (Pro). While characterizing some of the changes
      in solute accumulation in NaCl-stressed rice (Oryza sativa L.), we identified
      several other potential osmoprotectants. One such substance, trehalose, begins to
      accumulate in small amounts in roots after 3 d. We performed a series of
      experiments to compare the effects of Pro and trehalose on ion accumulation to
      determine whether the two chemicals protect the same physiological processes. We
      found that Pro either has no effect or, in some cases, exasperates the effect of
      NaCl on growth inhibition, chlorophyll loss, and induction of a highly sensitive
      marker for plant stress, the osmotically regulated salT gene. By contrast, low to
      moderate concentrations of trehalose reduce Na+ accumulation, salT expression,
      and growth inhibition. Somewhat higher concentrations (10 mM) prevent NaCl
      induced loss of chlorophyll in blades, preserve root integrity, and enhance
      growth. The results of this study indicate that during osmotic stress trehalose
      or carbohydrates might be more important for rice than Pro.

PMID- 12223798
TI  - Cold-Resistant and Cold-Sensitive Maize Lines Differ in the Phosphorylation of
      the Photosystem II Subunit, CP29.
AB  - The effects of low temperature on the relative contributions of the reaction
      center and the antenna activities to photosystem II (PSII) electron transport
      were estimated by chlorophyll fluorescence. The inhibition of PSII photochemistry
      resulted from photo-damage to the reaction center and/or a reduced probability of
      excitation energy trapping by the reaction center. Although chill treatment did
      not modify the proportion of the dimeric to monomeric PSII, it destabilized its
      main light-harvesting complex. Full protection of the reaction center was
      achieved only in the presence of the phosphorylated PSII subunit, CP29. In a
      nonphosphorylating genotype the chill treatment led to photoinhibitory damage.
      The phosphorylation of CP29 modified neither its binding to the PSII core nor its
      pigment content. Phosphorylated CP29 was isolated by flat-bed isoelectric
      focusing. Its spectral characteristics indicated a depletion of the chlorophyll
      spectral forms with the highest excitation transfer efficiency to the reaction
      center. It is suggested that phosphorylated CP29 performs its regulatory function
      by an yet undescribed mechanism based on a shift of the equilibrium for the
      excitation energy toward the antenna.

PMID- 12223799
TI  - The Effect of Elevated Partial Pressures of CO2 on the Relationship between
      Photosynthetic Capacity and N Content in Rice Leaves.
AB  - The effects of growth CO2 levels on the photosynthetic rates; the amounts of
      ribulose-1,5-bisphosphate carboxylase (Rubisco), chlorophyll (Chl), and
      cytochrome f; sucrose phosphate synthase activity; and total N content were
      examined in young, fully expanded leaves of rice (Oryza sativa L.). The plants
      were grown hydroponically under two CO2 partial pressures of 36 and 100 Pa at
      three N concentrations. The light-saturated photosynthesis at 36 Pa CO2 was lower
      in the plants grown in 100 Pa CO2 than those grown in 36 Pa CO2. Similarly, the
      amounts of Rubisco, Chl, and total N were decreased in the leaves of the plants
      grown in 100 Pa CO2. However, regression analysis showed no differences between
      the two CO2 treatments in the relationship between photosynthesis and total N or
      in the relationship between Rubisco and Chl and total N. Although a relative
      decrease in Rubisco to cytochrome f or sucrose phosphate synthase was found in
      the plants grown in 100 Pa CO2, this was the result of a decrease in total N
      content by CO2 enrichment. The activation state of Rubisco was also unaffected by
      growth CO2 levels. Thus, decreases in the photosynthetic capacity of the plants
      grown in 100 Pa CO2 could be simply accounted for by a decrease in the absolute
      amount of leaf N.

PMID- 12223800
TI  - Growth and N Allocation in Rice Plants under CO2 Enrichment.
AB  - The effects of CO2 enrichment on growth and N allocation of rice (Oryza sativa
      L.) were examined. The plants were grown hydroponically in growth chambers with a
      14-h photoperiod (1000 [mu]mol quanta m-2 s-1) and a day/night temperature of
      25/20[deg]C. From the 28th to 70th d after germination, the plants were exposed
      to two CO2 partial pressures, namely 36 and 100 Pa. The CO2 enrichment increased
      the final biomass, but this was caused by a stimulation of the growth rate during
      the first week of the exposure to elevated CO2 partial pressures. The
      disappearance of the initial stimulation of the growth rate was associated with a
      decreased leaf area ratio. Furthermore, CO2 enrichment decreased the investment
      of N in the leaf blades, whereas the N allocation into the leaf sheaths and roots
      increased. Thus, the decrease in leaf N content by CO2 enrichment was not due to
      dilution of N caused by a relative increase in the plant biomass but was due to
      the change in N allocation at the whole-plant level. We conclude that the growth
      responses of rice to CO2 enrichment are mainly controlled by leaf area expansion
      and N allocation into leaf blades at the whole-plant level.

PMID- 12223801
TI  - Pollination-Induced Ethylene in Carnation (Role of Stylar Ethylene in Corolla
      Senescence).
AB  - In carnation (Dianthus caryophyllus L. cv White Sim) cell to cell communication
      between the pollen and pistil induces ovary development and corolla senescence.
      The production of elevated ethylene by the style is the first measurable
      postpollination response. This is followed by a wave of ethylene production from
      the other floral organs. To investigate the regulation of ethylene biosynthesis
      in pollinated flowers we measured ethylene production and the expression of 1
      aminocyclopropane-1-carboxylate synthase and 1-aminocyclopropane-1-carboxylate
      oxidase transcripts in individual floral organs after pollination. Ethylene
      production by pollinated styles can be defined temporally by three distinct
      peaks. By pollinating a single style from a multistyle gynoecium, it was
      determined that the unpollinated style produces ethylene that corresponds to the
      first and third peaks observed from a pollinated style. Inhibition of ethylene
      action in the pollinated style by diazocyclopentadiene treatment prevented both
      pollination-induced corolla senescence and ethylene production from the ovaries
      and petals. Treatment with diazocyclopentadiene decreased stylar ethylene
      production during the second peak and completely inhibited the third peak of
      ethylene in both pollinated and unpollinated styles. This later auto-catalytic
      ethylene in styles is likely responsible for pollination-induced corolla
      senescence and ovary development.

PMID- 12223802
TI  - Physical and Kinetic Evidence for an Association between Sucrose-Phosphate
      Synthase and Sucrose-Phosphate Phosphatase.
AB  - The possible formation of a multienzyme complex between sucrose (Suc)-phosphate
      synthase (SPS) and Suc-phosphate phosphatase (SPP) was examined by measuring the
      rates of Suc-6-phosphate (Suc-6-P) synthesis and hydrolysis in mixing experiments
      with partially purified enzymes from spinach (Spinacia oleracea) and rice (Oryza
      sativa) leaves. The addition of SPP to SPS stimulated the rate of Suc-6-P
      synthesis. SPS inhibited the hydrolysis of exogenous Suc-6-P by SPP when added in
      the absence of its substrate (i.e. UDP-glucose) but stimulated SPP activity when
      the SPS substrates were present and used to generate Suc-6-P directly in the
      reaction. Results from isotope-dilution experiments suggest that Suc-6-P was
      channeled between SPS and SPP. A portion of the SPS activity comigrated with SPP
      during native polyacrylamide gel electrophoresis, providing physical evidence for
      an enzyme-enzyme interaction. Taken together, these results strongly suggest that
      SPS and SPP associate to form a multienzyme complex.

PMID- 12223803
TI  - Recovery from Heat Shock in Heat-Tolerant and Nontolerant Variants of Creeping
      Bentgrass.
AB  - Recovery from the heat-shock response was tested in heat-tolerant (selected
      bentgrass [SB]) and nontolerant (nonselected bentgrass [NSB]) variants of
      creeping bentgrass (Agrostis palustris Huds.) SB increased incorporation of
      radioactive amino acids into protein 2 h earlier than NSB when leaf blades were
      incubated at the recovery temperature following heat shock. Electrophoresis
      indicated that heat-shock protein (HSP) synthesis decreased and normal protein
      synthesis increased at 4 h in SB and at 6 to 8 h in NSB. Increased synthesis of
      normal proteins was not due to increased abundance of normal mRNAs, which were
      equivalent in SB and NSB at 4 h. But at 4 h, more of the normal mRNA population
      was associated with polysomes in SB than in NSB. Synthesis of HSP70 and HSP18
      decreased earlier in SB than in NSB. The decreased synthesis of these HSPs
      appeared to be correlated with decreased mRNA abundance. But at 4 h, some of the
      HSP18 mRNA may have been associated with heat-shock granules in SB. Synthesis of
      HSP25 continued through the 8-h recovery in both variants. Although the abundance
      of HSP25 was equivalent in SB and NSB during heat shock and recovery, more HSP25
      mRNA was associated with polysomes in SB than in NSB.

PMID- 12223804
TI  - Influence of Plant Growth at High CO2 Concentrations on Leaf Content of Ribulose
      1,5-Bisphosphate Carboxylase/Oxygenase and Intracellular Distribution of Soluble
      Carbohydrates in Tobacco, Snapdragon, and Parsley.
AB  - We have examined the possible role of leaf cytosolic hexoses and the expression
      of mannitol metabolism as mechanisms that may affect the repression of
      photosynthetic capacity when plants are grown at 1000 versus 380 [mu]L L-1 CO2.
      In plants grown at high CO2, leaf ribulose-1,5-bisphosphate carboxylase/oxygenase
      content declined by [greater than or equal to]20% in tobacco (Nicotiana
      sylvestris) but was not affected in the mannitol-producing species snapdragon
      (Antirrhinum majus) and parsley (Petroselinum hortense). In the three species
      mesophyll glucose and fructose at midday occurred almost entirely in the vacuole
      (>99%), irrespective of growth CO2 levels. The estimated cytosolic concentrations
      of glucose and fructose were [less than or equal to]100 [mu]M. In the three
      species grown at high CO2, total leaf carbohydrates increased 60 to 100%, but
      mannitol metabolism did not function as an overflow mechanism for the increased
      accumulation of carbohydrate. In both snapdragon and parsley grown at ambient or
      high CO2, mannitol occurred in the chloroplast and cytosol at estimated midday
      concentrations of 0.1 M or more each. The compartmentation of leaf hexoses and
      the metabolism of alternate carbohydrates are further considered in relation to
      photosynthetic acclimation to high levels of CO2.

PMID- 12223805
TI  - Ca2+ and Calmodulin Dynamics during Photopolarization in Fucus serratus Zygotes.
AB  - The role of Ca2+ in zygote polarization in fucoid algae (Fucus, Ascophyllum, and
      Pelvetia species) zygote polarization is controversial. Using a local source of
      Fucus serratus, we established that zygotes form a polar axis relative to
      unilateral light (photopolarization) between 8 and 14 h after fertilization (AF),
      and become committed to this polarity at approximately 15 to 18 h AF. We
      investigated the role of Ca2+, calmodulin, and actin during photopolarization by
      simultaneously exposing F. serratus zygotes to polarizing light and various
      inhibitors. Neither removal of Ca2+ from the culture medium or high
      concentrations of EGTA and LaCl3 had any effect on photopolarization. Bepridil,
      3,4,5-trimethoxybenzoic acid 8-(diethylamino) octyl ester, nifedipine, and
      verapamil, all of which block intracellular Ca2 release, reduced
      photopolarization from 75 to 30%. The calmodulin antagonists N-(6-aminohexyl)-5
      chloro-L-naphthalenesulfonamide and trifluoperazine inhibited photopolarization
      in all zygotes, whereas N-(6-aminohexyl)-L-naphthalenesulfonamide had no effect.
      Cytochalasin B, cytochalasin D, and latrunculin B, all of which inhibit actin
      polymerization, had no effect on photopolarization, but arrested polar axis
      fixation. The role of calmodulin during polarization was investigated further.
      Calmodulin mRNA from the closely related brown alga Macrocystis pyrifera was
      cloned and the protein was expressed in bacteria. Photopolarization was enhanced
      following microinjections of this recombinant calmodulin into developing zygotes.
      Confocal imaging of fluorescein isothiocyanate-labeled recombinant calmodulin in
      photopolarized zygotes showed a homogenous signal distribution at 13 h AF, which
      localized to the presumptive rhizoid site at 15 h AF.

PMID- 12223806
TI  - Effects of Prolonged Washing on Primary and Secondary Transport Processes at the
      Plasma Membrane in Red Beet Storage Tissue.
AB  - Changing patterns of enzyme activity and solute transport in response to washing
      were investigated in red beet (Beta vulgaris L.) storage tissue. Washing had a
      pronounced effect on the plasma membrane (PM) H+-ATPase with an increase in both
      hydrolytic and proton-pumping activities. Immunoblotting indicated that this may
      be due, in part, to a higher amount of this enzyme in the PM of washed tissue.
      Activities of the tonoplast (V)H+-ATPase and pyrophosphatase fluctuated during a
      4-d washing period, but overall showed no marked change in activity. In tissue
      discs sucrose (Suc), glucose (Glc), and fructose uptakes increased significantly
      in response to washing. Cycloheximide, cordycepin, and tunicamycin inhibited both
      Glc- and Suc-inducible uptake. Monensin also strongly inhibited inducible Glc
      uptake, but the effect on Suc was less marked. N-Ethylmaleimide inhibited both
      Suc and Glc uptake, with its effects being more pronounced in fresh tissue. Other
      protein-modifying reagents showed no significant difference in their level of
      inhibition between fresh and washed tissue. Transport studies, carried out using
      energized PM vesicles from fresh and washed tissue, indicated that there was no
      rise in Suc and Glc uptake rates in response to washing. Results with a range of
      inhibitors indicated that there was no marked change in transporter sensitivity
      in vesicles isolated from fresh and washed tissue. The results indicate that the
      well-described enhancement of solute transport in washed storage tissue may be
      due to an increased PM H+-ATPase activity rather than to changes in PM carrier
      activity or to changes in metabolism such as invertase activity.

PMID- 12223807
TI  - Salicylic Acid Is Needed in Hypersensitive Cell Death in Soybean but Does Not Act
      as a Catalase Inhibitor.
AB  - The function of salicylic acid (SA) in hypersensitive cell death was studied in a
      soybean (Glycine max)-Pseudomonas syringae pv glycinea system. The infection of
      cell cultures with bacteria leads to a hypersensitive reaction (HR), which is
      dependent on an appropriate avirulence gene and on low concentrations of SA. The
      requirement for SA is essential for a process shortly before the onset of the HR
      caused cell death 5 to 6 h after infection with bacteria. SA given 10 to 12 h
      after infection or preincubation cannot rescue the completion of the cell death
      program. SA does not inhibit catalase or ascorbate peroxidase in soybean. In
      addition, the in vivo capacity of the cell culture for the rapid metabolism of
      H2O2 is not altered by SA. This clearly shows that SA is needed for the HR-caused
      cell death for a reaction downstream of the oxidative burst. Lipid peroxides
      accumulate during the HR, but the loss of membrane control precedes the
      generation of lipid peroxides. The accumulation of lipid peroxides in the HR can
      be prevented by lipid antioxidants. Nevertheless, cell death kinetics remain
      unaltered in the presence of antioxidants. It is concluded that lipid peroxides
      are a consequence of cell death, but not the primary cause of it.

PMID- 12223808
TI  - Distribution of Folate Derivatives and Enzymes for Synthesis of 10
      Formyltetrahydrofolate in Cytosolic and Mitochondrial Fractions of Pea Leaves.
AB  - Leaf extracts of 14-d-old pea (Pisum sativum L. cv Homesteader) seedlings were
      examined for folate derivatives and for 10-formyltetrahydrofolate synthetase
      (SYN), 5,10-methenyltetrahydrofolate cyclohydrolase (CYC), and 5,10
      methylenetetrahydrofolate dehydrogenase (DHY) activities. Microbiological and
      enzyme assays showed that leaf folates SYN, CYC, and DHY were predominantly
      cytosolic. Extracts of Percoll gradient-purified mitochondria contained less than
      1% of total leaf folate and less that 1% of each enzyme activity. Fractionation
      of whole-leaf homogenates resulted in the copurification of DHY and CYC (subunit
      38 kD) and the isolation of a SYN protein (subunit 66 kD). Polyclonal antibodies
      were raised against purified cytosolic DHY-CYC (DHY-CYC-Ab) and cytosolic SYN
      (SYN-Ab), respectively. Immunoblots showed that DHY-CYC-Ab cross-reacted with a
      mitochondrial protein band (38 kD). Two mitochondrial protein bands (subunit Mr =
      40,000 and 44,000) cross-reacted with SYN-Ab. Immunoaffinity chromatography (DHY
      CYC-Ab as the immobile ligand) indicated that the bulk of mitochondrial SYN
      activity was not associated with mitochondrial DHY or CYC. When 9-d-old etiolated
      pea seedlings were exposed to light for up to 3 d, the specific enzyme activities
      of DHY-CYC in whole-leaf extracts rose 2-fold and more DHY-CYC-Ab cross-reacting
      protein was detected. In contrast, the specific activity of SYN fell from 5 to 1
      [mu]mol min-1 mg-1 protein and less SYN-Ab cross-reacting protein was detected.
      The data suggest that in pea leaves, the bulk of one-carbon-substituted
      tetrahydrofolates and enzymes for the generation of 10-formyltetrahydrofolate are
      extra-mitochondrial.

PMID- 12223809
TI  - The Polyadenylation of RNA in Plants.

PMID- 12223810
TI  - Gene Expression and Signal Transduction in Water-Stress Response.

PMID- 12223812
TI  - Is the High Basal Level of Salicylic Acid Important for Disease Resistance in
      Potato?
AB  - Potato (Solanum tuberosum) plants contain a high basal level of salicylic acid
      (SA), the role of which in disease resistance is currently unclear. Here we
      report that, in spite of a drastic reduction in total SA levels in transgenic
      potato plants expressing the bacterial salicylate hydroxylase gene (nahG), there
      was no significant increase in disease severity when infected by Phytophthora
      infestans. Therefore, the high basal level of SA does not lead to constitutive
      resistance in healthy potato plants. However, in contrast to control plants,
      arachidonic acid failed to induce systematic acquired resistance (SAR) in nahG
      plants against P. infestans, indicating an essential role of SA in potato SAR.
      These results suggest that in potato the development of SAR against P. infestans
      may involve increased sensitivity of the plant to SA.

PMID- 12223811
TI  - Actin Filaments Modulate Both Stomatal Opening and Inward K+-Channel Activities
      in Guard Cells of Vicia faba L.
AB  - Actin antagonists have previously been shown to alter responses of Commelina
      communis stomata to physiological stimuli, implicating actin filaments in the
      control of guard cell volume changes (M. Kim, P.K. Hepler, S.-O. Eun, K.S. Ha, Y.
      Lee [1995] Plant Physiol 109: 1077-1084). Since K+ channels in the guard cell
      play an important role in stomatal movements, we examined the possible regulation
      of K+-channel activities by the state of actin polymerization. Agents affecting
      actin polymerization altered light-induced stomatal opening and inward K+-channel
      activities measured by patch clamping in Vicia faba. Cytochalasin D, which
      induces depolymerization of actin filaments, promoted light-induced stomatal
      opening and potentiated the inward K+ current in guard cell protoplasts.
      Phalloidin, a stabilizer of filamentous actin, inhibited both light-induced
      stomatal opening and inward K+ current. Inward K+-channel activities in outside
      out membrane patches showed responses to these agents that support results at the
      whole-cell current level, suggesting that cytochalasin D facilitates and
      phalloidin inhibits K+ influx in intact guard cells, thus resulting in
      enhancement and inhibition of stomatal opening, respectively. To our knowledge,
      this is the first report that provides evidence that actin filaments may regulate
      an important physiological process by modulating the activities of ion channels
      in plant cells.

PMID- 12223813
TI  - Sym2 of Pea Is Involved in a Nodulation Factor-Perception Mechanism That Controls
      the Infection Process in the Epidermis.
AB  - In pea (Pisum sativum) up to 50 nodulation mutants are known, several of which
      are affected in the early steps of the symbiotic interaction with Rhizobium sp.
      bacteria. Here we describe the role of the sym2 gene in nodulation (Nod) factor
      perception. Our experiments show that the sym2A allele from the wild pea variety
      Afghanistan confers an arrest in infection-thread growth if the Rhizobium
      leguminosarum bv viciae strain does not produce Nod factors with a NodX-mediated
      acetylation at their reducing end. Since the induction of the early nodulin gene
      ENOD12 in the epidermis and the formation of a nodule primordium in the inner
      cortex were not affected, we conclude that more than one Nod factor-perception
      mechanism is active. Furthermore, we show that sym2A-mediated control of
      infection-thread growth was affected by the bacterial nodulation gene nodO.

PMID- 12223814
TI  - The Differential Expression of Sucrose Synthase in Relation to Diverse Patterns
      of Carbon Partitioning in Developing Cotton Seed.
AB  - Developing cotton (Gossypium hirsutum L.) seed exhibits complex patterns of
      carbon allocation in which incoming sucrose (Suc) is partitioned to three major
      sinks: the fibers, seed coat, and cotyledons, which synthesize cellulose, starch,
      and storage proteins or oils, respectively. In this study we investigated the
      role of Suc synthase (SuSy) in the mobilization of Suc into such sinks.
      Assessments of SuSy gene expression at various levels led to the surprising
      conclusion that, in contrast to that found for other plants, SuSy does not appear
      to play a role in starch synthesis in the cotton seed. However, our demonstration
      of functional symplastic connections between the phloem-unloading area and the
      fiber cells, as well as the SuSy expression pattern in fibers, indicates a major
      role of SuSy in partitioning carbon to fiber cellulose synthesis. SuSy expression
      is also high in transfer cells of the seed coat facing the cotyledons. Such high
      levels of SuSy could contribute to the synthesis of the thickened cell walls and
      to the energy generation for Suc efflux to the seed apoplast. The expression of
      SuSy in cotyledons also suggests a role in protein and lipid synthesis. In
      summary, the developing cotton seed provides an excellent example of the diverse
      roles played by SuSy in carbon metabolism.

PMID- 12223815
TI  - A G-Box-Binding Protein from Soybean Binds to the E1 Auxin-Response Element in
      the Soybean GH3 Promoter and Contains a Proline-Rich Repression Domain.
AB  - The E1 promoter fragment (-249 to -203) is one of three auxin-response elements
      (AuxREs) in the soybean (Glycine max L.) GH3 promoter (Z.-B. Liu, T. Ulmasov, X.
      Shi, G. Hagen, T.J. Guilfoyle [1994] Plant Cell 6: 645-657). Results presented
      here further characterize and delimit the AuxRE within the E1 fragment. The E1
      fragment functioned as an AuxRE in transgenic tobacco (Nicotiana tabacum L.)
      plants, as well as in transfected protoplasts. The AuxRE within E1 contains a G
      box, and this G-box was used to clone a G-box-binding factor (GBF) from soybean
      (SGBF-2). This 45-kD GBF contains an N-terminal proline-rich domain and a C
      terminal basic/leucine zipper DNA-binding domain. Gel-mobility shift assays were
      used to characterize the binding specificity of SGBF-2. Antiserum raised against
      recombinant SGBF-2 was used to further characterize SGBF-2 and antigenically
      related GBFs in soybean nuclear extracts. Co-transfection assays with effector
      and reporter plasmids in carrot (Daucus carota L.) protoplasts indicated that the
      N-terminal proline-rich domain of SGBF-2 functioned as a repression domain in
      both basal and auxin-inducible transcription.

PMID- 12223816
TI  - Tomato Polyphenol Oxidase (Differential Response of the Polyphenol Oxidase F
      Promoter to Injuries and Wound Signals).
AB  - Tomato (Lycopersicon esculentum Mill.) polyphenol oxidases (PPOs) are encoded by
      a seven-member gene family that exhibits complex patterns of differential
      expression during growth and differentiation. Antisense down-regulation of
      constitutive and induced PPO expression results in hypersusceptibility to
      pathogens, suggesting a critical role for PPO-mediated phenolic oxidation in
      plant defense. However, the nature and extent of PPO induction and its
      contribution to resistance are unclear. In this study we examined the
      inducibility of the tomato PPO gene family. In mature plants PPO transcript
      levels systemically increased in young leaves (nodes 1-3) when mature leaflets
      (node 5) were injured. Transcripts hybridizing to PPO E/F-specific probes were
      the predominant wound-induced PPO mRNAs in young leaves. Analysis of PPO
      promoter: GUS fusion constructs shows that mechanical wounding and infection by
      fungal and bacterial pathogens induced transcription of PPO F. Different
      injuries, salicylic acid, ethylene, and jasmonates elicited distinct, cell
      specific and developmental stage-specific patterns of PPO F expression. Whereas
      jasmonates and mechanical wounding significantly induced PPO F only in young
      leaves (nodes 1-3), and ethylene induced PPO F only in older leaves (node 7),
      salicylic acid induced PPO F in stems and foliage at all developmental stages.
      These results demonstrate that cis-element(s) sufficient for PPO F inducibility
      reside in the 5[prime] flanking region, and these elements are responsive to a
      broad range of signals.

PMID- 12223817
TI  - Activation of Host Defense Mechanisms by Elevated Production of H2O2 in
      Transgenic Plants.
AB  - Active oxygen species have been postulated to perform multiple functions in plant
      defense, but their exact role in plant resistance to diseases is not fully
      understood. We have recently demonstrated H2O2-mediated disease resistance in
      transgenic potato (Solanum tuberosum) plants expressing a foreign gene encoding
      glucose oxidase. In this study we provide further evidence that the H2O2-mediated
      disease resistance in potato is effective against a broad range of plant
      pathogens. We have investigated mechanisms underlying the H2O2-mediated disease
      resistance in transgenic potato plants. The constitutively elevated levels of
      H2O2 induced the accumulation of total salicylic acid severalfold in the leaf
      tissue of transgenic plants, although no significant change was detected in the
      level of free salicylic acid. The mRNAs of two defense-related genes encoding the
      anionic peroxidase and acidic chitinase were also induced. In addition, an
      increased accumulation of several isoforms of extracellular peroxidase, including
      a newly induced one, was observed. This was accompanied by a significant increase
      in the lignin content of stem and root tissues of the transgenic plants. The
      results suggest that constitutively elevated sublethal levels of H2O2 are
      sufficient to activate an array of host defense mechanisms, and these defense
      mechanisms may be a major contributing factor to the H2O2-mediated disease
      resistance in transgenic plants.

PMID- 12223818
TI  - Antisense Repression of Both ADP-Glucose Pyrophosphorylase and Triose Phosphate
      Translocator Modifies Carbohydrate Partitioning in Potato Leaves.
AB  - Previous experiments have shown that carbohydrate partitioning in leaves of
      potato (Solanum tuberosum L.) plants can be modified by antisense repression of
      the triose phosphate translocator (TPT), favoring starch accumulation during the
      light period, or by leaf-specific antisense repression of ADP-glucose
      pyrophosphorylase (AGPase), reducing leaf starch content. These experiments
      showed that starch and sucrose synthesis can partially replace each other. To
      determine how leaf metabolism acclimates to an inhibition of both pathways,
      transgenic potato (S. tuberosum L. cv Desiree) plants, with a 30% reduction of
      the TPT achieved by antisense repression, were transformed with an antisense cDNA
      of the small subunit of AGPase, driven by the leaf-specific ST-LS1 promoter.
      These double-transformed plants were analyzed with respect to their carbohydrate
      metabolism, and starch accumulation was reduced in all lines of these plants. In
      one line with a 50% reduction of AGPase activity, the rate of CO2 assimilation
      was unaltered. In these plants the stromal level of triose phosphate was
      increased, enabling a high rate of triose phosphate export in spite of the
      reduction of the TPT protein by antisense repression. In a second line with a 95%
      reduction of AGPase activity, the amount of chlorophyll was significantly reduced
      as a consequence of the lowered triose phosphate utilization capacity.

PMID- 12223819
TI  - Separation of Photolabile-Phytochrome and Photostable-Phytochrome Actions on
      Growth and Microtubule Orientation in Maize Coleoptiles (A Physiological
      Approach).
AB  - For separating the physiological actions of photolabile (phy-l) and photostable
      phytochromes, we compared the effects of red (R) and far-red (FR) light on
      elongation growth and microtubule reorientation in segments of maize (Zea mays
      L.) coleoptiles raised either in darkness (phy-l present) or preirradiated with R
      (phy-l eliminated). In 4.5-d-old dark-grown seedlings R first promoted growth and
      induced a transverse microtubule orientation. In continuous R the phytochrome
      action responsible for these responses was replaced by an opposite phytochrome
      action that produced a stable growth inhibition and longitudinal microtubule
      orientation. In R-preirradiated segments only the second type of phytochrome
      action could be observed. Reversion experiments with FR light pulses demonstrated
      that both types of phytochrome action were dependent on the FR-absorbing form of
      phytochrome and mirrored the actual phytochrome state after 1 h. We conclude from
      these and related results that growth promotion and transverse microtubule
      orientation are mediated by phy-l, whereas growth inhibition and longitudinal
      microtubule orientation are mediated by photostable phytochrome. The opposite
      actions of the two phytochromes can be separated by preirradiating the seedlings
      with R. Photoresponsiveness ascribed to phy-l disappeared after 5 d. phy-l
      appears to play a distinct but transitory role in coleoptile development.

PMID- 12223820
TI  - Identification of a Transport Mechanism for NH4+ in the Symbiosome Membrane of
      Pea Root Nodules.
AB  - Symbiosome membrane vesicles, facing bacteroid-side-out, were purified from pea
      (Pisum sativum L.) root nodules and used to study NH4+ transport across the
      membrane by recording vesicle uptake of the NH4+ analog [14C]methylamine (MA).
      Membrane potentials ([delta][psi]) were imposed on the vesicles using K+
      concentration gradients and valinomycin, and the size of the imposed [delta][psi]
      was determined by measuring vesicle uptake of [14C]tetraphenylphosphonium.
      Vesicle uptake of MA was driven by a negative [delta][psi] and was stimulated by
      a low extravesicular pH. Protonophore-induced collapse of the pH gradient
      indicated that uptake of MA was not related to the presence of a pH gradient. The
      MA-uptake mechanism appeared to have a large capacity for transport, and
      saturation was not observed at MA concentrations in the range of 25 [mu]M to 150
      mM. MA uptake could be inhibited by NH4+, which indicates that NH4+ and MA
      compete for the same uptake mechanism. The observed fluxes suggest that voltage
      driven channels are operating in the symbiosome membrane and that these are
      capable of transporting NH4+ at high rates from the bacteroid side of the
      membrane to the plant cytosol. The pH of the symbiosome space is likely to be
      involved in regulation of the flux.

PMID- 12223821
TI  - Mannitol Protects against Oxidation by Hydroxyl Radicals.
AB  - Hydroxyl radicals may be responsible for oxidative damage during drought or
      chilling stress. We have shown that the presence of mannitol in chloroplasts can
      protect plants against oxidative damage by hydroxyl radicals (B. Shen, R.G.
      Jensen, H.J. Bohnert [1997] Plant Physiol 113: 1177-1183). Here we identify one
      of the target enzymes that may be protected by mannitol. Isolated thylakoids in
      the presence of physiological concentrations of Fe2+ generated hydroxyl radicals
      that were detected by the conversion of phenylalanine into tyrosine. The activity
      of phosphoribulokinase (PRK), a thiol-regulated enzyme of the Calvin cycle, was
      reduced by 65% in illuminated thylakoids producing hydroxyl radicals. Mannitol
      (125 mM) and sodium formate (15 mM), both hydroxyl radical scavengers, and
      catalase (3000 units mL-1) prevented loss of PRK activity. In contrast,
      superoxide dismutase (300 units mL-1) and glycine betaine (125 mM) were not
      effective in protecting PRK against oxidative inactivation. Ribulose-1,5
      bisphosphate carboxylase/oxygenase activity was not affected by hydroxyl
      radicals. We suggest that the stress-protective role of mannitol may be to shield
      susceptible thiol-regulated enzymes like PRK plus thioredoxin, ferredoxin, and
      glutathione from inactivation by hydroxyl radicals in plants.

PMID- 12223822
TI  - Solubilization and Separation of a Plant Plasma Membrane NADPH-O2- Synthase from
      Other NAD(P)H Oxidoreductases.
AB  - Solubilization and ion-exchange chromatography of plasma membrane proteins
      obtained from bean (Phaseolus vulgaris L.) seedlings resulted in a single NAD(P)H
      O2--synthase protein peak. This enzyme showed a high preference toward NADPH as a
      substrate (reaction rate, 27.4 nmol O2- produced min-1 mg-1 protein), whereas
      NADH reactions ranged from 0 to maximally 15% of the NADPH reactions. The protein
      functions as an oxidase and it was clearly resolved from NAD(P)H dehydrogenases
      identified with commonly used strong oxidants (ferricyanide, cytochrome c, DCIP,
      and oxaloacetate). The involvement of peroxidases in O2- production is excluded
      on the basis of potassium-cyanide insensitivity and NADPH specificity. The NADPH
      oxidase is only moderately stimulated by flavins (1.5-fold with 25 [mu]M flavine
      adenine dinucleotide and 2.5-fold with 25 [mu]M flavin mononucleotide) and
      inhibited by 100 [mu]M p-chloromercuribenzenesulfonic acid, 200 [mu]M
      diphenyleneiodonium, 10 mM quinacrine, 40 mM pyridine, and 20 mM imidazole. The
      presence of flavins was demonstrated in the O2-synthase fraction, but no b-type
      cytochromes were detected. The effect of these inhibitors and the detection of
      flavins and cytochromes in the plant O2- synthase make it possible to compare
      this enzyme with the NADPH O2- synthase of animal neutrophil cells.

PMID- 12223823
TI  - Genetic Enhancement of the Ability to Tolerate Photoinhibition by Introduction of
      Unsaturated Bonds into Membrane Glycerolipids.
AB  - Strong light leads to damage to photosynthetic machinery, particularly at low
      temperatures, and the main site of the damage is the D1 protein of the
      photosystem II (PSII) complex. Here we describe that transformation of
      Synechococcus sp. PCC 7942 with the desA gene for a [delta]12 desaturase
      increased unsaturation of membrane lipids and enhanced tolerance to strong light.
      To our knowledge, this is the first report of the successful genetic enhancement
      of tolerance to strong light. Analysis of the light-induced inactivation and of
      the subsequent recovery of the activity of the PSII complex revealed that the
      recovery process was markedly accelerated by the genetic transformation. Labeling
      experiments with [35S]L-methionine also revealed that the synthesis of the D1
      protein de novo at low temperature, which was a prerequisite for the restoration
      of the PSII complex, was much faster in the transformed cells than in the wild
      type cells. These findings demonstrate that the ability of membrane lipids to
      desaturate fatty acids is important for the photosynthetic organisms to tolerate
      strong light, by accelerating the synthesis of the D1 protein de novo.

PMID- 12223825
TI  - A Radial Concentration Gradient of Indole-3-Acetic Acid Is Related to Secondary
      Xylem Development in Hybrid Aspen.
AB  - The radial distribution pattern of indole-3-acetic acid (IAA) was determined
      across the developing tissues of the cambial region in the stem of hybrid aspen
      (Populus tremula L. x Populus tremuloides Michx). IAA content was measured in
      consecutive tangential cryo-sections using a microscale mass spectrometry
      technique. Analysis was performed with wild-type and transgenic trees with an
      ectopic expression of Agrobacterium tumefaciens IAA-biosynthetic genes. In all
      tested trees IAA was distributed as a steep concentration gradient across the
      developing tissues of the cambial region. The peak level of IAA was within the
      cambial zone, where cell division takes place. Low levels were reached in the
      region where secondary wall formation was initiated. The transgenic trees
      displayed a lower peak level and a wider radial gradient of IAA compared with the
      wild type. This alteration was related to a lower rate of cambial cell division
      and a longer duration of xylem cell expansion in the transgenic trees, resulting
      in a decreased xylem production and a larger fiber lumen area. The results
      indicate that IAA has a role in regulating not only the rate of physiological
      processes such as cell division, but also the duration of developmental processes
      such as xylem fiber expansion, suggesting that IAA functions as a morphogen,
      conveying positional information during xylem development.

PMID- 12223824
TI  - Characterization of Water Channels in Wheat Root Membrane Vesicles.
AB  - The functional significance of water channels in wheat (Triticum aestivum L.)
      root membranes was assessed using light scattering to measure vesicle shrinking
      in response to osmotic gradients rapidly imposed in a stopped flow apparatus.
      Vesicles were obtained from both a plasma membrane fraction and a plasma membrane
      depleted endomembrane fraction including tonoplast vesicles. Osmotic water
      permeability (Pos) in the endomembrane fraction was high (Pos= 86.0 [mu]m s-1)
      with a low activation energy (EA= 23.32 kJ mol-1 [plus or minus] 3.88 SE), and
      was inhibited by mercurials (K1= 40 [mu]M HgCl2, where K1 is the inhibition
      constant for half-maximal inhibition), suggesting participation of water
      channels. A high ratio of osmotic to diffusional permeability (Pd) (using D2O as
      a tracer, Pos/Pd = 7 [plus or minus] 0.5 SE) also supported this view. For the
      endomembrane fraction there was a marked decrease in Pos with increasing osmotic
      gradient that was not observed in the plasma membrane fraction. Osmotic water
      permeability in the plasma membrane fraction was lower (Pos= 12.5 [mu]m s-1) with
      a high activation energy (EA= 48.07 kJ mol-1 [plus or minus] 3.63 SE) and no
      mercury inhibition. Nevertheless, Pos/Pd was found to be substantially higher
      than one (Pos= 3 [plus or minus] 0.2 SE), indicating that water channels mediated
      water flow in this fraction, too. Possible distortion of the Pos/Pd value by
      unstirred layer effects was shown to be unlikely.

PMID- 12223826
TI  - Estimation of Polymer Rigidity in Cell Walls of Growing and Nongrowing Celery
      Collenchyma by Solid-State Nuclear Magnetic Resonance in Vivo.
AB  - When the growth of a plant cell ceases, its walls become more rigid and lose the
      capacity to extend. Nuclear magnetic resonance relaxation methods were used to
      determine the molecular mobility of cell wall polymers in growing and nongrowing
      live celery (Apium graveolens L.) collenchyma. To our knowledge, this is the
      first time this approach has been used in vivo. Decreased polymer mobility in
      nongrowing cell walls was detected through the 13C-nuclear magnetic resonance
      spectrum by decreases in the proton spin-spin relaxation time constant and in the
      intensity of a sub-spectrum corresponding to highly mobile pectins, which was
      obtained by a spectral editing technique based on cross-polarization rates.
      Flexible, highly methyl-esterified pectins decreased in relative quantity when
      growth ceased. A parallel increase in the net longitudinal orientation of
      cellulose microfibrils was detected in isolated cell walls by polarized Fourier
      transformed infrared spectrometry.

PMID- 12223827
TI  - Molecular Rigidity in Dry and Hydrated Onion Cell Walls.
AB  - Solid-state nuclear magnetic resonance relaxation experiments can provide
      information on the rigidity of individual molecules within a complex structure
      such as a cell wall, and thus show how each polymer can potentially contribute to
      the rigidity of the whole structure. We measured the proton magnetic relaxation
      parameters T2 (spin-spin) and T1p (spin-lattice) through the 13C-nuclear magnetic
      resonance spectra of dry and hydrated cell walls from onion (Allium cepa L.)
      bulbs. Dry cell walls behaved as rigid solids. The form of their T2 decay curves
      varied on a continuum between Gaussian, as in crystalline solids, and
      exponential, as in more mobile materials. The degree of molecular mobility that
      could be inferred from the T2 and T1p decay patterns was consistent with a
      crystalline state for cellulose and a glassy state for dry pectins. The theory of
      composite materials may be applied to explain the rigidity of dry onion cell
      walls in terms of their components. Hydration made little difference to the
      rigidity of cellulose and most of the xyloglucan shared this rigidity, but the
      pectic fraction became much more mobile. Therefore, the cellulose/xyloglucan
      microfibrils behaved as solid rods, and the most significant physical distinction
      within the hydrated cell wall was between the microfibrils and the predominantly
      pectic matrix. A minor xyloglucan fraction was much more mobile than the
      microfibrils and probably corresponded to cross-links between them. Away from the
      microfibrils, pectins expanded upon hydration into a nonhomogeneous, but much
      softer, almost-liquid gel. These data are consistent with a model for the stress
      bearing hydrated cell wall in which pectins provide limited stiffness across the
      thickness of the wall, whereas the cross-linked microfibril network provides much
      greater rigidity in other directions.

PMID- 12223828
TI  - Impacts of CO2 Enrichment on Productivity and Light Requirements of Eelgrass.
AB  - Seagrasses, although well adapted for submerged existence, are CO2-limited and
      photosynthetically inefficient in seawater. This leads to high light requirements
      for growth and survival and makes seagrasses vulnerable to light limitation. We
      explored the long-term impact of increased CO2 availability on light
      requirements, productivity, and C allocation in eelgrass (Zostera marina L.).
      Enrichment of seawater CO2 increased photosynthesis 3-fold, but had no long-term
      impact on respiration. By tripling the rate of light-saturated photosynthesis,
      CO2 enrichment reduced the daily period of irradiance-saturated photosynthesis
      (Hsat) that is required for the maintenance of positive whole-plant C balance
      from 7 to 2.7 h, allowing plants maintained under 4 h of Hsat to perform like
      plants growing in unenriched seawater with 12 h of Hsat. Eelgrass grown under 4 h
      of Hsat without added CO2 consumed internal C reserves as photosynthesis rates
      and chlorophyll levels dropped. Growth ceased after 30 d. Leaf photosynthesis,
      respiration, chlorophyll, and sucrose-phosphate synthase activity of CO2-enriched
      plants showed no acclimation to prolonged enrichment. Thus, the CO2-stimulated
      improvement in photosynthesis reduced light requirements in the long term,
      suggesting that globally increasing CO2 may enhance seagrass survival in
      eutrophic coastal waters, where populations have been devastated by algal
      proliferation and reduced water-column light transparency.

PMID- 12223829
TI  - Sucrose Accumulation in the Sugarcane Stem Is Regulated by the Difference between
      the Activities of Soluble Acid Invertase and Sucrose Phosphate Synthase.
AB  - To assess the relative importance of morphological and biochemical factors in the
      regulation of sucrose (Suc) accumulation in the sugarcane (Saccharum spp.
      hybrids) stem, we investigated morphological and biochemical correlates of Suc
      accumulation among parents and progeny of a family segregating for differences.
      In contrast to the parents, no relationship was observed between morphology and
      the level of Suc accumulation among the progeny. The level and timing of Suc
      accumulation in the whole stalk and within individual internodes was correlated
      with the down-regulation of soluble acid invertase (SAI) activity. High SAI
      activity prevented most, but not all, Suc accumulation. There was a critical
      threshold of SAI activity above which high concentrations of Suc did not
      accumulate. This low level of SAI activity was always exceeded in the internodes
      of the lower-Suc-storing genotypes. However, low activity of SAI was not
      sufficient by itself to account for the Suc accumulation in the higher-Suc
      storing genotypes. Major differences in Suc accumulation among the population
      were attributed to the difference between activities of SAI and Suc phosphate
      synthase, provided SAI is below the critical threshold concentration. This result
      is not unexpected, since the pathway of Suc transport for storage involves Suc
      hydrolysis and resynthesis.

PMID- 12223830
TI  - Changes in Mitochondrial Respiratory Chain Components of Petunia Cells during
      Culture in the Presence of Antimycin A.
AB  - When petunia (Petunia hybrida Vilm, cv Rosy Morn) cells are cultured in the
      presence of 2 [mu]M antimycin A (AA), respiration proceeds mainly via the cyanide
      resistant pathway. Cyanide-resistant respiratory rates were higher in
      mitochondria from AA cells than in control mitochondria. Compared with control
      cells, an increase in alternative oxidase protein was observed in AA cells, as
      well as an increase in ubiquinone (UQ) content. A change in the kinetics of
      succinate dehydrogenase was observed: there was a much higher activity at high UQ
      reduction in mitochondria from AA cells compared with control mitochondria. No
      changes were found for external NADH dehydrogenase kinetics. In AA cells in vivo,
      UQ reduction was only slightly higher than in control cells, indicating that
      increased electron transport via the alternative pathway can prevent high UQ
      reduction levels. Moreover, O2 consumption continues at a similar rate as in
      control cells, preventing O2 danger. These adaptations to stress conditions, in
      which the cytochrome pathway is restricted, apparently require, in addition to an
      increase in alternative oxidase protein, a new setup of the relative amounts
      and/or kinetic parameters of all of the separate components of the respiratory
      network.

PMID- 12223831
TI  - Abolition of Posttranscriptional Regulation of Nitrate Reductase Partially
      Prevents the Decrease in Leaf NO3- Reduction when Photosynthesis Is Inhibited by
      CO2 Deprivation, but Not in Darkness.
AB  - The activity of nitrate reductase (NR) in leaves is regulated by light and
      photosynthesis at transcriptional and posttranscriptional levels. To understand
      the physiological role of these controls, we have investigated the effects of
      light and CO2 on in vivo NO3- reduction in transgenic plants of Nicotiana
      plumbaginifolia lacking either transcriptional regulation alone or
      transcriptional and posttranscriptional regulation of NR. The abolition of both
      levels of NR regulation did not modify the light/dark changes in exogenous 15NO3-
      reduction in either intact plants or detached leaves. The same result was
      obtained for 15N incorporation into free amino acids in leaves after 15NO3- was
      supplied to the roots, and for reduction of endogenous NO3- after transfer of the
      plants to an N-deprived solution. In the light, however, deregulation of NR at
      the posttranscriptional level partially prevented the inhibition of leaf 15NO3-
      reduction resulting from the removal of CO2 from the atmosphere We concluded from
      these observations that in our conditions deregulation of NR in the transformants
      investigated had little impact on the adverse effect of darkness on leaf NO3-
      reduction, and that posttranscriptional regulation of NR is one of the mechanisms
      responsible for the short-term coupling between photosynthesis and leaf NO3-
      reduction in the light.

PMID- 12223832
TI  - Desensitization and Dark Recovery of the Photoreceptor Current in Chlamydomonas
      reinhardtii.
AB  - Photoexcitation of rhodopsin in Chlamydomonas reinhardtii triggers a complex of
      rapid bioelectric processes in the cell membrane. Photoreceptor and flagellar
      currents are the major components of this cascade and are the basis for the
      phototaxis and photoshock response, respectively. Desensitization and dark
      recovery of the extracellularly recorded photoreceptor current were investigated
      in double-flash excitation experiments. The data obtained show that the
      desensitization is determined by membrane depolarization rather than by rhodopsin
      bleaching. At external K+ concentrations less than 0.6 mM, generation of the
      flagellar current triggers a transient, depolarization-activated K+ efflux that
      contributes to membrane repolarization after light excitation. Acceleration of
      the dark recovery at 5 to 10 mM Ca2+ can be partially attributed to a blockade of
      K+ influx, which is triggered at higher external K+ concentrations. K+ currents
      constitute a novel component of the rhodopsin-mediated signaling system in C.
      reinhardtii that is involved in the process of dark adaptation of the system.

PMID- 12223833
TI  - Cellulose and Callose Biosynthesis in Higher Plants (I. Solubilization and
      Separation of (1->3)- and (1->4)-[beta]-Glucan Synthase Activities from Mung
      Bean).
AB  - (1->3)- and (1->4)-[beta]-glucan synthase activities from higher plants have been
      physically separated by gel electrophoresis in nondenaturing conditions. The two
      glucan synthases show different mobilities in native polyacrylamide gels. Further
      separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed
      a different polypeptide composition in these synthases. Three polypeptides (64,
      54, and 32 kD) seem to be common to both synthase activities, whereas two
      polypeptides (78 and 38 kD) are associated only with callose synthase activity.
      Twelve polypeptides (170, 136, 108, 96, 83, 72, 66, 60, 52, 48, 42, and 34 kD)
      appear to be specifically associated with cellulose synthase activity. The
      successful separation of (1->3)- and (1->-4)-[beta]-glucan synthase activities
      was based on the manipulation of digitonin concentrations used in the
      solubilization of membrane proteins. At low dipitomin concentrations (0.05 and
      0.1%), the ratio of the cellulose to callose synthase activity was higher. At
      higher digitonin (0.5-1%) concentrations, the ratio of the callose to cellulose
      synthase activity was higher. Rosette-like particles with attached product were
      observed in samples taken from the top of the stacking gel, where only cellulose
      was synthesized. Smaller (nonrosette) particles were found in the running gel,
      where only callose was synthesized. These findings suggest that a higher level of
      subunit organization is required for in vitro cellulose synthesis in comparison
      with callose assembly.

PMID- 12223834
TI  - Possible Involvement of Al-Induced Electrical Signals in Al Tolerance in Wheat.
AB  - The relationship between Al-induced depolarization of root-cell transmembrane
      electrical potentials (Em) and Al tolerance in wheat (Triticum aestivum L.) was
      investigated. Al exposure induced depolarizations of Em in the Al-tolerant wheat
      cultivars Atlas and ET3, but not in the Al-sensitive wheat cultivars Scout and
      ES3. The depolarizations of Em occured in root cap cells and as far back as 10 mm
      from the root tip. The depolarization was specific to Al3+; no depolarization was
      observed when roots were exposed to the rhizotoxic trivalent cation La3+. The Al
      induced depolarization occurred in the presence of anion-channel antagonists that
      blocked the release of malate, indicating that the depolarization is not due to
      the electrogenic efflux of malate2-. K+-induced depolarizations in the root cap
      were of the same magnitude as Al-induced depolarizations, but did not trigger
      malate release, indicating that Al-induced depolarization of root cap cell
      membrane potentials is probably linked to, but is not sufficient to trigger,
      malate release.

PMID- 12223835
TI  - Chlorophyll Breakdown in Senescent Chloroplasts (Cleavage of Pheophorbide a in
      Two Enzymic Steps).
AB  - The cleavage of pheophorbide (Pheide) a into primary fluoescent chlorophyll (Chl)
      catabolites (pFCCs) in senescent chloroplasts was investigated. Chloroplast
      preparations isolated from senescent canola (Brassica napus) cotyledons exhibited
      light-dependent production of pFCC when assay mixtures were supplemented with
      ferredoxin (Fd). pFCC production in detergent-solubilized membranes was dependent
      on the presence of an Fd-reducing system. Pheide a cleavage required the action
      of two proteins, Pheide a oxygenase and a stroma protein. In the absence of
      stroma protein, Pheide a oxygenase converted Pheide a into a red Chl catabolite
      (RCC), the presumptive intermediary product of Pheide a cleavage. Incubation of
      the stroma protein (RCC reductase) together with chemically synthesized RCC
      resulted in the production of three different FCCs. Two of these catabolites were
      identical to the pFCCs from canola or barley (Hordeum vulgare) (pFCC-1) and sweet
      pepper (Capsicum annuum) (pFCC-2), respectively. Thus, the conversion of Pheide a
      to pFCC could be demonstrated to proceed in two consecutive steps, and both
      reactions depended on reduced Fd as the source of electrons. The function of Fd
      in Chl breakdown in vivo is corroborated by the marked retention of this protein
      until the late stages of senescence, as demonstrated by immunoblotting.

PMID- 12223836
TI  - Partial Purification and Characterization of Red Chlorophyll Catabolite
      Reductase, a Stroma Protein Involved in Chlorophyll Breakdown.
AB  - Red chlorophyll (Chl) catabolite (RCC) reductase, which catalyzes the reaction of
      an intermediary Chl catabolite (RCC) in the two-step cleavage reaction of
      pheophorbide (Pheide) a into primary fluorescent catabolites (pFCCs) during Chl
      breakdown, was characterized and partially purified. RCC reductase activity was
      present at all stages of barley leaf development and even in roots. The highest
      specific activity was found in senescent leaves, which were used to purify RCC
      reductase 1000-fold. Among the remaining three proteins, RCC reductase activity
      was most likely associated with a 55-kD protein. RCC reductase exhibited
      saturation kinetics for RCC, with an apparent Michaelis constant of 0.6 mM. The
      reaction depended on reduced ferredoxin and was sensitive to oxygen. Assays of
      purified RCC reductase with chemically synthesized RCC as a substrate yielded
      three different FCCs, two of which could be identified as the stereoisomeric
      pFCCs from canola (Brassica napus) (pFCC-1) and sweet pepper (Capsicum annuum)
      (pFCC-2), respectively. In the coupled reaction with Pheide a oxidase and RCC
      reductase, either pFCC-1 or pFCC-2 was produced, depending on the plant species
      employed as a source of RCC reductase. Data from 18 species suggest that the
      stereospecific action of RCC reductase is uniform within a plant family.

PMID- 12223837
TI  - A Secreted Factor Inducs Cell Expansion and Formation of Metaxylem-Like Tracheary
      Elements in Xylogenic Suspension Cultures of Zinnia.
AB  - Conditioned medium from mesophyll cell-suspension cultures of Zinnia elegans L.
      has striking effects on cell expansion and tracheary element differentiation when
      applied to cultures of freshly isolated mesophyll cells. These effects include
      (a) induction of early cell expansion, (b) delay in differentiation by 48 h or
      more, (c) reduction in the synchrony of differentiation, and (d) early formation
      of very large, metaxylem-like tracheary elements. Like reduced osmotic potential
      and buffering at pH 5.5, conditioned medium appears to have its primary effect on
      cell expansion. Partial characterization of the expansion-inducing factor
      indicates that it is heat stable, of low molecular mass, and is resistant to
      protease. It also binds reversibly to concanavalin A but is not adsorbed by
      charcoal. We suggest that the secreted factor may be an oligosaccharide involved
      in the coordination of cell expansion and differentiation and the regulation of
      the protoxylem-like to metaxylem-like transition in xylogenic suspension
      cultures.

PMID- 12223838
TI  - Transgenic Tobacco Plants Expressing Pea Chloroplast Nmdh cDNA in Sense and
      Antisense Orientation (Effects on NADP-Malate Dehydrogenase Level, Stability of
      Transformants, and Plant Growth).
AB  - A full-length cDNA encoding light-activated chloroplast NADP-malate dehydrogenase
      (NADP-MDH) (EC 1.1.1.82) from pea (Pisum sativum L.) was introduced in the sense
      and antisense orientation into tobacco (Nicotiana tabacum L.). Transgenic plants
      with decreased or increased expression levels were obtained. Because of
      substantial age-dependent differences in individual leaves of a single plant,
      standardization of NADP-MDH levels was required first. Then, extent and stability
      of over- or under-expression of Nmdh, the gene encoding NADP-MDH, was
      characterized in the various transformants. Frequently, cosuppression effects
      were observed, indicating sufficient homology between the endogenous tobacco and
      the heterologous pea gene. Analysis of the T1 and T2 progeny of a series of
      independent transgenic lines revealed that NADP-MDH capacity ranged between 10%
      and [greater than or equal to]10-fold compared with the wild type. Under ambient
      conditions whole-plant development, growth period, and fertility were unaffected
      by NADP-MDH reduction to 20% of the wild-type level; below this threshold plant
      growth was retarded. A positive growth effect was registered in young plants with
      stably enhanced NADP-MDH levels within a defined developmental window.

PMID- 12223839
TI  - Effect of Antisense Suppression of Endopolygalacturonase Activity on Polyuronide
      Molecular Weight in Ripening Tomato Fruit and in Fruit Homogenates.
AB  - Fruit of tomato (Lycopersicon esculentum Mill.) in which endopolygalacturonase
      (PG) activity had been suppressed to <1% of wild-type levels were slightly firmer
      than nontransgenic controls later in ripening. Enzymically inactive cell walls
      were prepared from these ripening fruit using Tris-buffered phenol. When
      extracted with chelator followed by Na2CO3, the amounts of pectin solubilized
      from cell walls of nontransgenic control or from transgenic antisense PG fruit
      were similar. Size-exclusion chromatography analysis showed that, relative to
      controls, in antisense PG fruit polyuronide depolymerization was delayed in the
      chelator-soluble fraction throughout ripening and reduced in the Na2CO3-soluble
      fraction at the overripe stage. Reduced pectin depolymerization rather than
      altered extractability thus may have contributed to enhanced fruit firmness.
      Substantially larger effects of suppressed PG activity were detected in tomato
      fruit homogenates processed to paste. In control paste the majority of the
      polyuronide was readily soluble in water and was very highly depolymerized. In
      antisense PG paste the proportion of polyuronide solubilized by water was
      reduced, and polyuronides retained a high degree of polymerization. The
      suppression of fruit PG activity thus has a small effect on polyuronide
      depolymerization in the fruit but a much larger effect in paste derived from
      these fruit. This indicates that in the cell wall PG-mediated degradation of
      polyuronide is normally restricted but that in tissue homogenates or in isolated
      cell walls this restriction is removed and extensive pectin disassembly results
      unless PG is inactivated.

PMID- 12223840
TI  - L-myo-lnositol 1-Phosphate Synthase from Plant Sources (Characteristics of the
      Chloroplastic and Cytosolic Enzymes).
AB  - L-myo-inositol 1-phosphate synthase (EC 5.5.1.4) from cyanobacterial (Spirulina
      platensis), algal (Euglena gracilis), and higher plant (Oryza sativa, Vigna
      radiata) sources was purified to electrophoretic homogeneity, biochemically
      characterized, and compared. Both chloroplastic and cytosolic forms of the enzyme
      were detected in E. gracilis, O. sativa, and V. radiata, whereas only the
      cytosolic form was detected in streptomycin-bleached or chloroplastic mutants of
      E. gracilis and in S. platensis. Both the chloroplastic and cytosolic forms from
      different sources could be purified following the same three-step chromatographic
      protocol. L-myo-inositol 1-phosphate synthases purified from these different
      sources do not differ significantly with respect to biochemical and kinetic
      parameters except for the molecular mass of the chloroplastic and cytosolic
      native holoenzymes, which appear to be homotetrameric and homotrimeric
      associations of their constituent subunits, respectively. Monovalent and divalent
      cations, sugar alcohols, and sugar phosphates are inhibitory to the enzyme
      activity. N-ethylmaleimide inhibition of synthase activity could be protected by
      the combined presence of the substrate glucose-6-phosphate and cofactor NAD+.
      Antibody raised against the cytosolic enzyme from E. gracilis immunoprecipitates
      and cross-reacts with both chloroplastic and cytosolic forms from the other
      sources studied.

PMID- 12223841
TI  - Ethylene-Mediated Programmed Cell Death during Maize Endosperm Development of
      Wild-Type and shrunken2 Genotypes.
AB  - We characterized the progression of programmed cell death during maize (Zea mays
      L.) endosperm development of starchy (Su; wild-type) and shrunken2 (sh2)
      genotypes and tested the involve ment of ethylene in mediating this process.
      Histological and viability staining demonstrated that endosperm cell death was
      initiated earlier and progressed more rapidly in sh2 endosperm compared with Su
      endosperm. Internucleosomal DNA fragmentation accompanied endosperm cell death
      and occurred more extensively in sh2 endosperm. 1-Aminocyclopropane-1-carboxylic
      acid levels peaked approximately 16 d after pollination (dap) in Su endosperm and
      gradually decreased during subsequent development, whereas two large 1
      aminocyclopropane-1-carboxylic acid peaks were observed in sh2 endosperm, the
      first between 16 and 20 dap and the second at 36 dap. Ethylene levels were
      elevated in sh2 kernels compared with Su kernels, with an initial peak 20 dap
      approximately 3-fold higher than in Su kernels and a second peak 36 dap
      approximately 5-fold higher than that in Su kernels. Ethylene treatment of Su
      kernels resulted in earlier and more extensive endosperm cell death and DNA
      fragmentation. Aminoethoxyvinylglycine treatment of sh2 kernels reduced the
      extent of DNA fragmentation. We conclude that ethylene is involved in triggering
      programmed cell death in developing maize endosperm and is responsible for the
      aberrant phenotype of sh2 kernels.

PMID- 12223843
TI  - Photoregulation of Chloroplast Gene Transcription in the Chromophytic Alga
      Heterosigma carterae.
AB  - Light acts as a complex regulator of cellular development and gene expression in
      photoautotrophs. Although light signals are highly effective in controlling
      cellular division and chloroplast biogenesis in the toxic marine alga Heterosigma
      carterae, their influence on gene expression has not been well characterized. To
      address this need cultures of H. carterae synchronized by an alternating light
      dark regime were sampled through 12 h of light and 12 h of dark to characterize
      cell division, chloroplast complement, and chloroplast RNA abundance. These
      studies have identified a unimodal pattern of chloroplast transcriptional
      activity for a suite of cellular and photosynthetic genes. To determine the
      alga's response to a change in photoperiod, 12-h light/12-h dark-synchronized
      cultures were transferred to constant light and then periodically sampled.
      Although cellular and chloroplast division cycles remained synchronized in
      constant conditions for 24 h, the transcriptional apparatus responded by
      increasing ctRNA abundance within 45 min of the change in photoperiod. However,
      the ability of the alga to mount this rapid transcriptional response was limited
      to the first 2 h of the putative dark period. Thus, the chloroplast
      transcriptional apparatus of H. carterae may initiate a rapid, temporally gated
      response to a change in photoperiod that is independent of ongoing light
      entrained cellular and chloroplast division cycles.

PMID- 12223842
TI  - A Vacuole-Associated Annexin Protein, VCaB42, Correlates with the Expansion of
      Tobacco Cells.
AB  - A Ca-dependent membrane-binding protein of the annexin family, VCaB42, has
      previously been shown to associate with vacuolar vesicles at physiological levels
      of Ca. In this study we used suspension-cultured cells of tobacco (Nicotiana
      tabacum BY-2) to show that VCaB42 is enriched 4.5-fold in intact vacuoles,
      whereas evacuolated protoplasts show a 12-fold reduction in VCaB42. VCaB42
      distribution is thus comparable to that of the vacuole-associated H+-ATPase but
      is distinct from the endoplasmic reticulum-localized protein calnexin. Because
      VCaB42 is a vacuole-associated annexin, and given the putative function of
      annexins in vesicle fusion, we hypothesize a role for this protein in the
      vacuolation process of expanding cells. Consistent with this hypothesis, we show
      that VCaB42 levels correlate with age-associated and hormonally induced changes
      in cell volume in tobacco suspension cultures. The association of VCaB42 with
      vacuoles and its correlative pattern of expression relative to the expansion of
      cells is consistent with a possible role for VCaB42 in the early events of
      vacuole biogenesis.

PMID- 12223844
TI  - The Effects of Salicylic Acid and Tobacco Mosaic Virus Infection on the
      Alternative Oxidase of Tobacco.
AB  - Salicylic acid (SA) is a signal in systemic acquired resistance and an inducer of
      the alternative oxidase protein in tobacco (Nicotiana tabacum cv Xanthi nc) cell
      suspensions and during thermogenesis in aroid spadices. The effects of SA on the
      levels of alternative oxidase protein and the pathogenesis-related 1a mRNA (a
      marker for systemic acquired resistance), and on the partitioning of electrons
      between the Cyt and alternative pathways were investigated in tobacco. Leaves
      were treated with 1.0 mM SA and mitochondria isolated at times between 1 h and 3
      d after treatment. Alternative oxidase protein increased 2.5-fold within 5 h,
      reached a maximum (9-fold) after 12 h, and remained at twice the level of control
      plants after 3 d. Measurements of isotope fractionation of 18O by intact leaf
      tissue gave a value of 23% at all times, identical to that of control plants,
      indicating a constant 27 to 30% of electron-flow partitioning to the alternative
      oxidase independent of treatment with SA. Transgenic NahG tobacco plants that
      express bacterial salicylate hydroxylase and possess very low levels of SA gave a
      fractionation of 23% and showed control levels of alternative oxidase protein,
      suggesting that steady-state alternative oxidase accumulates in an SA-independent
      manner. Infection of plants with tobacco mosaic virus resulted in an increase in
      alternative oxidase protein in both infected and systemic leaves, but no increase
      was observed in comparably infected NahG plants. Total respiration rate and
      partitioning of electrons to the alternative pathway in virus-infected plants was
      comparable to that in uninfected controls.

PMID- 12223845
TI  - Quantum Yields and Rate Constants of Photochemical and Nonphotochemical
      Excitation Quenching (Experiment and Model).
AB  - Sunflower (Helianthus annuus L.), cotton (Gossypium hirsutum L.), tobacco
      (Nicotiana tabacum L.), sorghum (Sorghum bicolor Moench.), amaranth (Amaranthus
      cruentus L.), and cytochrome b6f complex-deficient transgenic tobacco leaves were
      used to test the response of plants exposed to differnt light intensities and CO2
      concentrations before and after photoinhibition at 4000 [mu]mol photons m-2 s-1
      and to thermoinhibition up to 45[deg]C. Quantum yields of photochemical and
      nonphotochemical excitation quenching (YP and YN) and the corresponding relative
      rate constants for excitation capture from the antenna-primary radical pair
      equilibrium system (k[prime]P and k[prime]N) were calculated from measured
      fluorescence parameters. The above treatments resulted in decreases in YP and
      K[prime]P and in approximately complementary increases in YN and K[prime]N under
      normal and inhibitory conditions. The results were reproduced by a mathematical
      model of electron/proton transport and O2 evolution/CO2 assimilation in
      photosynthesis based on budget equations for the intermediates of photosynthesis.
      Quantitative differences between model predictions and experiments are
      explainable, assuming that electron transport is organized into domains that
      contain relatively complete electron and proton transport chains (e.g.
      thylakoids). With the complementation that occurs between the photochemical and
      nonphotochemical excitation quenching, the regulatory system can constantly
      maintain the shortest lifetime of excitation necessary to avoid the formation of
      chlorophyll triplet states and singlet oxygen.

PMID- 12223846
TI  - Sodium Dodecyl Sulfate-Stable Proteases in Chloroplasts.
AB  - Chloroplast subfractions were monitored for sodium dodecyl sulfate-stable
      proteases. Nine distinct activities in the molecular mass range from 14 to 66 kD
      have been detected. Five of the proteases associated with thylakoid membranes
      belong to the serine and cysteine types of proteases. These activities could be
      preserved and purified by a two-step electrophoresis procedure.

PMID- 12223847
TI  - Purification and Characterization of Phosphoribosylpyrophosphate Synthetase from
      Rubber Tree Latex.
AB  - Phosphoribosylpyrophosphate synthetase (PRS; EC 2.7.6.1) from Hevea brasiliensis
      Mull. Arg. latex was located in the cytosol. After purification, its apparent
      molecular weight under nondenaturing conditions was estimated at 200,000 [plus or
      minus] 10,000; a single band at 57,000 [plus or minus] 3,000 was detected after
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme seemed to
      be a homotetramer. Its affinity constants were estimated at 200 [plus or minus]
      30 [mu]M for adenosine triphosphate and 40 [plus or minus] 2 [mu]M for ribose-5
      phosphate. The purified enzyme proved to be functional in a paraphysiological
      medium (cytosol deproteinized by ultrafiltration). Optimum pH was 7.5 in buffer
      and 6.5 in a paraphysiological medium. No PRS activity was detected in the
      absence of the Mg2+ ion. Of the numerous compounds tested, only Mn2+,
      phosphoribosylpyrophosphate, and inorganic phosphate affected the enzymatic
      reaction. Mn2+ (inhibitor constant = 20 [mu]M) and phosphoribosylpyrophosphate
      (inhibitor constant = 30 [mu]M) were inhibitors. PRS responded allosterically
      (Hill's coefficient = 2.3) to ribulose-5-phosphate in the presence of a
      physiological concentration of inorganic phosphate (10 mM). These results are set
      in the physiological context of laticifers.

PMID- 12223848
TI  - Rapid and Transient Activation of a Myelin Basic Protein Kinase in Tobacco Leaves
      Treated with Harpin from Erwinia amylovora.
AB  - Harpins are bacterial protein elicitors that induce hypersensitive response-like
      necrosis when infiltrated into nonhost plants such as tobacco (Nicotiana tabacum
      L.) (Z.-M. Wei, R.J. Laby, C.H. Zumoff, D.W. Bauer, S.Y. He, A. Collmer, S.V.
      Beer [1992] Science 257: 85-88). Activity of a 49-kD Mg2+-dependent and Ca2+
      independent kinase in tobacco leaves increased 50-fold 15 min after infiltration
      of harpin from Erwinia amylovora (harpinEa). Much less pronounced and more
      transient activation was detected in water-infiltrated leaves. Biochemical
      characteristics of the harpinEa-activated protein kinase (HAPK) activity are
      consistent with those of the mitogen-activated protein kinase family. HAPK is
      cytosolic and phosphorylates myelin basic protein on serine/threonine residues.
      Treatment with a protein tyrosine phosphatase completely eliminated HAPK
      activity, suggesting that tyrosine phosphorylation is required for
      posttranslational activation. Sustained HAPK activation after cycloheximide
      treatment implies that HAPK may be negatively regulated by a translation
      dependent mechanism. The extracellular Ca2+ chelator EGTA or the protein kinase
      inhibitor K252a, infiltrated in planta together with harpinEa, partially blocked
      HAPK activation. The Ca2+-channel blocker La3+ had no effect on HAPK activation,
      suggesting that phosphorylation events precede and/or do not depend on the entry
      of extracellular Ca2+ into the cell. These results suggest that early signal
      transduction events during harpinEa- induced hypersensitive response elicitation
      depend in part on the activation of HAPK.

PMID- 12223849
TI  - Occam's Razor Applied to Hormonology (Are Cytokinins Produced by Plants?).

PMID- 12223850
TI  - Root Lectins and Rhizobia.

PMID- 12223851
TI  - Membrane Fluidity and Temperature Perception.

PMID- 12223852
TI  - Evidence for the Presence of a Porin in the Membrane of Glyoxysomes of Castor
      Bean.
AB  - Glyoxysomes of endosperm tissue of castor bean (Ricinus communis L.) seedlings
      were solubilized in a detergent and added to a lipid bilayer. Conductivity
      measurements revealed that the glyoxysomal preparation contained a porin-like
      channel. Using an electrophysiological method, which we established for
      semiquantitative determination of porin activity, we were able to demonstrate
      that glyoxysomal membranes purified by sucrose density gradient centrifugation
      contain an integral membrane protein with porin activity. The porin of
      glyoxysomes was shown to have a relatively small single-channel conductance of
      about 330 picosiemens in 1 M KCl and to be strongly anion selective. Thus, the
      glyoxysomal porin differs from the other previously characterized porins in the
      outer membrane of mitochondria or plastids, but is similar to the porin of
      spinach (Spinacia oleracea L.) leaf peroxisomes. Our results suggest that, in
      analogy to the porin of leaf peroxisomes, the glyoxysomal porin facilitates the
      passage of small metabolites, such as succinate, citrate, malate, and aspartate,
      through the membrane.

PMID- 12223853
TI  - Source Strength Regulates an Early Phase Transition of Tobacco Shoot
      Morphogenesis.
AB  - We have taken advantage of specific reductions in the ribulose-1,5-bisphosphate
      carboxylase/oxygenase concentration in rbcS antisense mutants of tobacco
      (Nicotiana tabacum L.) to assess the contribution of source strength
      (carbohydrate production) to the control of shoot development. Wild-type and
      antisense plants undergo distinct phases of shoot development that can be
      distinguished from one another on the basis of differences in stem elongation
      rates, internode distances, plastochron indices, leaf sizes, and leaf
      morphologies. An early phase of shoot morphogenesis is markedly prolonged in the
      antisense plants, and an increased number of leaves emerge during this phase in
      the mutants. This delay is specific, inasmuch as the duration and expression of
      traits characteristic of later phases of shoot development proceed normally. In
      addition to altered shoot developmental patterns, the antisense mutants have
      enhanced shoot/root ratios and markedly increased leaf longevities. It is likely
      that these are adaptations that enhance photosynthetic rates. Consistent with
      this proposal, the total leaf areas and dry weights of the mutant and wild type
      are similar at flowering. Collectively, our results indicate that source strength
      regulates the duration of an early phase of tobacco shoot development and the
      transition to a later phase. We suggest that this phase change may occur in
      response to the attainment of a threshold source strength, which is delayed in
      the mutant plants.

PMID- 12223854
TI  - Genetic Transformation of Wheat Mediated by Agrobacterium tumefaciens.
AB  - A rapid Agrobacterium tumefaciens-mediated transformation system for wheat was
      developed using freshly isolated immature embryos, precultured immature embryos,
      and embryogenic calli as explants. The explants were inoculated with a disarmed
      A. tumefaciens strain C58 (ABI) harboring the binary vector pMON18365 containing
      the [beta]-glucuronidase gene with an intron, and a selectable marker, the
      neomycin phosphotransferase II gene. Various factors were found to influence the
      transfer-DNA delivery efficiency, such as explant tissue and surfactants present
      in the inoculation medium. The inoculated immature embryos or embryogenic calli
      were selected on G418-containing media. Transgenic plants were regenerated from
      all three types of explants. The total time required from inoculation to the
      establishment of plants in soil was 2.5 to 3 months. So far, more than 100
      transgenic events have been produced. Almost all transformants were
      morphologically normal. Stable integration, expression, and inheritance of the
      transgenes were confirmed by molecular and genetic analysis. One to five copies
      of the transgene were integrated into the wheat genome without rearrangement.
      Approximately 35% of the transgenic plants received a single copy of the
      transgenes based on Southern analysis of 26 events. Transgenes in T1 progeny
      segregated in a Mendelian fashion in most of the transgenic plants.

PMID- 12223855
TI  - Temporal Changes in State Transitions and Photosystem Organization in the
      Unicellular, Diazotrophic Cyanobacterium Cyanothece sp. ATCC 51142.
AB  - The unicellular Cyanobacterium Cyanothece sp. ATCC 51142, grown under alternating
      12-h light/12-h dark conditions, temporally separated N2 fixation from
      photosynthesis. The regulation of photosynthesis was studied using fluorescence
      spectra and kinetics to determine changes in state transitions and photosystem
      organization. The redox poise of the plastoquinone (PQ) pool appeared to be
      central to this regulation. Respiration supported N2 fixation by oxidizing
      carbohydrate granules, but reduced the PQ pool. This induced state 2 photosystem
      II monomers and lowered the capacity for O2 evolution. State 2 favored
      photosystem I trimers and cyclic electron transport, which could stimulate N2
      fixation; the stimulation suggested an ATP limitation to N2 and CO2 fixation. The
      exhaustion of carbohydrate granules at around 6 h in the dark resulted in reduced
      respiratory electron flow, which led to a more oxidized PQ pool and produced a
      sharp transition from state 2 to state 1. This transient state 1 returned to
      state 2 in the remaining hours of darkness. In the light phase, photosystem II
      dimerization correlated with increased phycobilisome coupling to photosystem II
      (state 1) and increased rates of O2 evolution. However, dark adaptation did not
      guarantee state 2 and left photosystem I centers in a mostly monomeric state at
      certain times.

PMID- 12223856
TI  - Histone Hyperacetylation in Maize in Response to Treatment with HC-Toxin or
      Infection by the Filamentous Fungus Cochliobolus carbonum.
AB  - HC-toxin, the host-selective toxin produced by the filamentous fungus
      Cochliobolus carbonum, inhibits maize (Zea mays L.) histone deacetylases (HDs) in
      vitro. Here we show that HDs are also inhibited by HC-toxin in vivo, as
      demonstrated by the accumulation of hyperacetylated forms of the core
      (nucleosomal) histones H3.1, H3.2, H3.3, and H4 in both maize embryos and tissue
      cultures. Hyperacetylation of H4 and all isoforms of H3 in tissue cultures of
      inbred Pr (genotype hm/hm) occurred at 10 ng/mL (23 nM). The effect was host
      selective; acetylation of histones in the near isogenic inbred Pr1 (genotype
      Hm/Hm) did not occur in tissue cultures or embryos treated with 0.2 [mu]g/mL or
      10 [mu]g/mL HC-toxin, respectively. Hyperacetylation of histone H4 in embryos of
      Pr1 began to occur at 50 [mu]g/mL. HC-toxin, and 200 [mu]g/mL HC-toxin caused
      equal hyperacetylation in Pr and Pr1 embryos. Hyperacetylated core histones,
      especially of the isoforms of histone H3, accumulated in leaves of inbred Pr, but
      not Pr1, after infection by toxin-producing strains of C. carbonum. Accumulation
      of hyperacetylated histones began at 24 h after inoculation, before the
      development of visible disease symptoms. Hyperacetylation of H2A or H2B histones
      were not detected in any of the studies. The results are consistent with HD being
      a primary site of action of HC-toxin.

PMID- 12223857
TI  - Gas Exchange and C Allocation in Dunaliella salina Cells in Response to the N
      Source and CO2 Concentration Used for Growth.
AB  - The halotolerant alga Dunaliella salina was cultured on 10 mM NH4+ or NO3- with
      air CO2 or 5% (v/v) CO2. Cells grown on NH4+ rather than NO3- were up to 17%
      larger in volume but had similar division rates. The photosynthetic K0.5 of
      dissolved inorganic C per cell was reduced, but the light- and CO2-saturated
      photosynthesis, dark respiration, and light-independent fixation rates were
      increased. The cells exhibited 2- to 5-fold greater activities of ribulose-1,5
      bisphosphate carboxylase/oxygenase, phosphoenolpyruvate carboxylase and
      carboxykinase, and carbonic anhydrase and more soluble and ribulose-1,5
      bisphosphate carboxylase/oxygenase protein. Chlorophyll and [beta]-carotene also
      increased by 30 to 70%. However, starch and glycerol decreased, indicating that C
      was reallocated from carbohydrates into protein and pigments by growth on NH4+.
      Algae cultured on air-CO2 rather than a high CO2 concentration were 44% smaller
      with 55 to 67% lower cell division rates and thus appeared C-limited, despite the
      operation of a CO2-concentrating mechanism. Cells cultured on air-CO2 had less
      protein and starch and 28% more glycerol, but the pigment content was unchanged.
      In only one growth regime was the cell glycerol concentration sufficient to
      maintain osmotic equilibrium with the external medium, indicating that an
      additional osmoticum was required. It appears that the N source, as well as the
      growth [CO2], substantially modifies photosynthetic and growth characteristics,
      light-independent C metabolism, and C-allocation patterns of D. salina cells.

PMID- 12223858
TI  - Characterization of Thylakoid-Derived Lipid-Protein Particles Bearing the Large
      Subunit of Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase.
AB  - Lipid-protein particles bearing the 55-kD ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco) (EC 4.1.1.39) large subunit (RLSU) and no
      detectable corresponding Rubisco small subunit (RSSU) were isolated from the
      stroma of intact chloroplasts by flotation centrifugation. Stromal RLSU-bearing
      particles appear to originate from thylakoids because they can also be generated
      in vitro by illumination of isolated thylakoids. Their formation in vitro is
      largely heat denaturable and is facilitated by light or ATP. RLSU-containing
      lipid-protein particles range from 0.05 to 0.10 [mu]m in radius, contain the same
      fatty acids as thylakoids, but have a 10- to 15-fold higher free-to-esterified
      fatty acid ratio than thylakoids. RLSU-bearing lipid-protein particles with no
      detectable RSSU were also immunopurified from the populations of both stromal
      lipid-protein particles and those generated in vitro from illuminated thylakoids.
      Protease shaving indicated that the RLSU is embedded in the lipid-protein
      particles and that there is also a protease-protected RLSU in thylakoids. These
      observations collectively indicate that the RLSU associated with thylakoids is
      released into the stroma by light-facilitated blebbing of lipid-protein
      particles. The release of RLSU-containing particles may in turn be coordinated
      with the assembly of Rubisco holoenzyme because chaperonin 60 is also associated
      with lipid-protein particles isolated from stroma.

PMID- 12223859
TI  - Characterization of the Variation Potential in Sunflower.
AB  - A major candidate for intercellular signaling in higher plants is the stimulus
      induced systemic change in membrane potential known as variation potential (VP).
      We investigated the mechanism of occurrence and long-distance propagation of VP
      in sunflower (Helianthus annuus L.) plants. Here we present evidence of the
      relationship among injury-induced changes in xylem tension, turgor pressure, and
      electrical potential. Although locally applied wounding did trigger a change in
      membrane potential, it evoked even faster changes in tissue deformation,
      apparently resulting from pressure surges rapidly transmitted through the xylem
      and experienced throughout the plant. Externally applied pressure mimicked flame
      wounding by triggering an electrical response resembling VP. Our findings suggest
      that VP in sunflower is not a propagating change in electrical potential and not
      the consequence of chemicals transmitted via the xylem, affecting ligand
      modulated ion channels. Instead, VP appears to result from the surge in pressure
      in the xylem causing a change in activity of mechanosensitive, stretch-responsive
      ion channels or pumps in adjacent, living cells. The ensuing ion flux evokes
      local plasma membrane depolarization, which is monitored extracellularly as VP.

PMID- 12223860
TI  - Apoplasmic and Protoplasmic Water Transport through the Parenchyma of the Potato
      Storage Organ.
AB  - Stationary volume fluxes through living and denatured parenchyma slices of the
      potato (Solanum tuberosum L.) storage organ were studied to estimate the
      hydraulic conductivity of the cell wall and to evaluate the significance of water
      transport through protoplasts, cell walls, and intercellular spaces. Slices were
      placed between liquid compartments, steady-state fluxes induced by pressure or
      concentration gradients of low- and high-molecular-mass osmotica were measured,
      and water transport pathways were distinguished on the basis of their difference
      in limiting pore size. The protoplasts were the dominating route for osmotically
      driven water transport through living slices, even in the case of a polymer
      osmoticum that is excluded from cell walls. The specific hydraulic conductivity
      of the cell wall matrix is too small to allow a significant contribution of the
      narrow cell wall bypass to water flow through the living tissue. This conclusion
      is based on (a) ultrafilter coefficients of denatured parenchyma slices, (b) the
      absence of a significant difference between ultrafilter coefficients of the
      living tissue slices for osmotica with low and high cell wall reflection
      coefficients, and (c) the absence of a significant interaction (solvent drag)
      between apoplasmic permeation of mannitol and the water flux caused by a
      concentration difference of excluded polyethylene glycol. Liquid-filled
      intercellular spaces were the dominating pathways for pressure-driven volume
      fluxes through the parenchyma tissue.

PMID- 12223861
TI  - RNase Activities Are Reduced Concomitantly with Conservation of Total Cellular
      RNA and Ribosomes in O2-Deprived Seedling Roots of Maize.
AB  - The effect of O2 deprivation on the activities of RNases and levels of total
      cellular RNA and ribosomes in seedling roots of maize (Zea mays L.) was
      investigated. Sodium dodecyl sulfate-polyacrylamide gels containing RNA were used
      to distinguish RNase isoenzymes by apparent molecular mass. Since O2 deprivation
      causes a decrease in cytosolic pH from approximately pH 7.4 to 6.4 and an
      elevation in cytosolic Ca2+, RNase levels were examined in the physiological
      range of cytosolic pH and in the presence of Ca2+, Mg2+, Zn2+,
      ethylenediaminetetracetate, or ethyleneglycol-bis([beta]-aminoethyl ether)
      N,N[prime]-tetraacetic acid. The activity of a number of RNases present in
      aerobic roots was reduced in response to O2 deprivation. Several RNases with a pH
      optimum of 6.4 were rapidly down-regulated by O2 deprivation. Spectrophotometric
      assay of extracts revealed that RNase activity was higher at pH 6.4 than at 7.2,
      and ethylenediaminetetracetate-insensitive RNase activity decreased in response
      to O2 deprivation. The decrease in RNase activity was correlated with no loss of
      total cellular RNA or ribosomes, despite a 4-fold decrease in run-on
      transcription of rRNA in isolated nuclei. Regulation of RNase activity may
      facilitate the conservation of nontranslating ribosomes and poorly translated
      mRNAs during O2 deprivation.

PMID- 12223862
TI  - Sorption of Aluminum to Plasma Membrane Vesicles Isolated from Roots of Scout 66
      and Atlas 66 Cultivars of Wheat.
AB  - To further elucidate the mechanisms of differential genotypic tolerance to Al,
      plasma membrane (PM) vesicles were isolated from whole roots, root tips, and
      tipless roots of Al3+-sensitive and Al3+-tolerant cultivars (cv) of wheat
      (Triticum aestivum L. cv Scout 66 and cv Atlas 66, respectively). Vesicles from
      cv Scout root tips sorbed more Al than vesicles prepared from any other source.
      The intrinsic surface-charge density of vesicles isolated from cv Scout was 26%
      more negative than vesicles from cv Atlas (-37.2 versus -29.5 millicoulombs m-2).
      Growth experiments indicated that cv Scout is slightly more sensitive to La3+
      than is cv Atlas, that the cultivars are equally sensitive to H+, and that cv
      Atlas is slightly more sensitive to SeO42-. The difference in sensitivity to Al3+
      was very large; for a 50% inhibition, a 16-fold greater activity of Al3+ was
      required for cv Atlas. Using a newly developed Gouy-Chapman-Stern model for ion
      sorption to the PM together with growth-response curves, we estimate that the
      difference in surface-charge density can account for the slightly greater
      sensitivity of cv Scout to cationic toxicants and the slightly greater
      sensitivity of cv Atlas to anionic toxicants. According to our estimates the
      differences in PM surface negativity and Al sorptive capacity probably account
      for some of the difference in sensitivity to Al3+, but the greater part of the
      difference probably arises from other tolerance mechanisms expressed in cv Atlas
      root tips that reduce the amount of Al3+ that can reach the PM.

PMID- 12223863
TI  - Substrate Kinetics of the Plant Mitochondrial Alternative Oxidase and the Effects
      of Pyruvate.
AB  - The kinetics of alternative oxidase (AOX) of Arum italicum spadices and soybean
      (Glycine max L.) cotyledons were studied both with intact mitochondria and with a
      solubilized, partially purified enzyme. Ubiquinone analogs were screened for
      their suitability as substrates and ubiquinol-1 was found to be most suitable.
      The kinetics of ubiquinol-1 oxidation via AOX in both systems followed Michaelis
      Menten kinetics, suggesting that the reaction is limited by a single-step
      substrate reaction. The kinetics are quite different from those previously
      described, in which the redox state of ubiquinone-10 was monitored and an
      increase in substrate was accompanied by a decrease in product. The difference
      between the systems is discussed. Pyruvate is a potent activator of the enzyme
      and its presence is essential for maximum activity. The addition of pyruvate to
      the solubilized enzyme increased the maximum initial velocity from 6.2 [plus or
      minus] 1.3 to 16.9 [plus or minus] 2.8 [mu]mol O2 mg-1 protein min-1 but had
      little effect on the Michaelis constant for ubiquinol-1, an analog of ubiquinol,
      which changed from 116 [plus or minus] 73 to 157 [plus or minus] 68 [mu]M. It is
      concluded that pyruvate (and presumably other keto acids) increases the activity
      of AOX but does not increase its affinity for its substrate. In agreement with
      this is the finding that removal of pyruvate (using lactate dehydrogenase and
      NADH) leads to an 80 to 90% decrease in the reaction rate, suggesting that
      pyruvate is important in the mechanism of reaction of AOX. The removal of
      pyruvate from the enzyme required turnover, suggesting that pyruvate is bound to
      the enzyme and is released during turnover.

PMID- 12223864
TI  - Treatment of Grape Berries, a Nonclimacteric Fruit with a Synthetic Auxin,
      Retards Ripening and Alters the Expression of Developmentally Regulated Genes.
AB  - Treatment of grape (Vitis vinifera L.) berries with the synthetic auxin-like
      compound benzothiazole-2-oxyacetic acid (BTOA) caused a delay in the onset of
      ripening of approximately 2 weeks. This was manifested as a retardation of the
      increases in berry weight, color, deformability, and hexose concentration. BTOA
      treatment also delayed by 2 weeks the increase in abscisic acid level that
      normally accompanies ripening and altered the expression of a number of
      developmentally regulated genes. A putative vacuolar invertase, which is normally
      expressed from berry set until ripening and turned off after ripening commences,
      remained expressed throughout development in BTOA-treated grape berries. This
      elevated expression resulted in increased levels of invertase activity. In
      contrast, the up-regulation of four other genes normally switched on at the time
      of ripening was delayed in BTOA-treated fruit. These included chalcone synthase
      and UDP-glucose-flavonoid 3-O-glucosyl transferase, both of which are involved in
      anthocyanin synthesis, a chitinase, and a ripening-related gene of an unknown
      function. These observations support the view that auxins (perhaps in conjunction
      with abscisic acid) may have a role in the control of grape berry ripening by
      affecting the expression of genes involved in the ripening process.

PMID- 12223865
TI  - Expressing an RbcS Antisense Gene in Transgenic Flaveria bidentis Leads to an
      Increased Quantum Requirement for CO2 Fixed in Photosystems I and II.
AB  - It was previously shown with concurrent measurements of gas exchange and carbon
      isotope discrimination that the reduction of ribulose-1,5-bisphosphate
      carboxylase/oxygenase by an antisense gene construct in transgenic Flaveria
      bidentis (a C4 species) leads to reduced CO2 assimilation rates, increased bundle
      sheath CO2 concentration, and leakiness (defined as the ratio of CO2 leakage to
      the rate of C4 acid decarboxylation; S. von Caemmerer, A. Millegate, G.D.
      Farquhar, R.T. Furbank [1997] Plant Physiol 113: 469-477). Increased leakiness in
      the transformants should result in an increased ATP requirement per mole of CO2
      fixed and a change in the ATP-to-NADPH demand. To investigate this, we compared
      measurements of the quantum yield of photosystem I and II ([phi]PSI and
      [phi]PSII) with the quantum yield of CO2 fixation ([phi]CO2) in control and
      transgenic F. bidentis plants in various conditions. Both [phi]PSI/[phi]CO2 and
      [phi]PSII/[phi]CO2 increased with a decrease in ribulose-1,5-bisphosphate
      carboxylase/oxygenase content, confirming an increase in leakiness. In the wild
      type the ratio of [phi]PSI to [phi]PSII was constant at different irradiances but
      increased with irradiance in the transformants, suggesting that cyclic electron
      transport may be higher in the transformants. To evaluate the relative
      contribution of cyclic or linear electron transport to extra ATP generation, we
      developed a model that links leakiness, ATP/NADP requirements, and quantum
      yields. Despite some uncertainties in the light distribution between photosystem
      I and II, we conclude from the increase of [phi]PSII/[phi]CO2 in the
      transformants that cyclic electron transport is not solely responsible for ATP
      generation without NADPH production.

PMID- 12223866
TI  - Elevated CO2 Effects during Leaf Ontogeny (A New Perspective on Acclimation).
AB  - For many plants growth in elevated CO2 leads to reduced rates of photosynthesis.
      To examine the role that leaf ontogeny plays in the acclimation response, we
      monitored photosynthesis and some related parameters at short intervals
      throughout the ontogenetic development of tobacco (Nicotiana tabacum L.) leaves
      under ambient (350 [mu]L L-1)- and high (950 [mu]L L-1)-CO2 conditions. The
      pattern of photosynthetic rate over time was similar between the two treatments
      and consistent with the expected pattern for a typical dicot leaf. However, the
      photosynthesis pattern in high-CO2-grown tobacco was shifted temporally to an
      earlier maximum and subsequent senescent decline. Ribulose-1,5-biphosphate
      carboxylase/oxygenase activity appeared to be the main factor regulating
      photosynthetic rates in both treatments. Therefore, we propose a new model for
      interpreting the acclimation response. Lowered photosynthetic rates observed
      during acclimation appear to be the result of a shift in the timing of the normal
      photosynthetic stages of leaf ontogeny to an earlier onset of the natural decline
      in photosynthetic rates associated with senescence.

PMID- 12223867
TI  - Increased Salt and Drought Tolerance by D-Ononitol Production in Transgenic
      Nicotiana tabacum L.
AB  - A cDNA encoding myo-inositol O-methyltransferase (IMT1) has been transferred into
      Nicotiana tabacum cultivar SR1. During drought and salt stress, transformants
      (I5A) accumulated the methylated inositol D-ononitol in amounts exceeding 35
      [mu]mol g-1 fresh weight In I5A, photosynthetic CO2 fixation was inhibited less
      during salt stress and drought, and the plants recovered faster than wild type.
      One day after rewatering drought-stressed plants, I5A photosynthesis had
      recovered 75% versus 57% recovery with cultivar SR1 plants. After 2.5 weeks of
      250 mM NaCl in hydroponic solution, I5A fixed 4.9 [plus or minus] 1.4 [mu]mol CO2
      m-2 s-1, whereas SR1 fixed 2.5 [plus or minus] 0.6 [mu]mol CO2 m-2 s-1. myo
      Inositol, the substrate for IMT1, increases in tobacco under stress.
      Preconditioning of I5A plants in 50 mM NaCl increased D-ononitol amounts and
      resulted in increased protection when the plants were stressed subsequently with
      150 mM NaCl. Pro, Suc, Fru, and Glc showed substantial diurnal fluctuations in
      amounts, but D-ononitol did not. Plant transformation resulting in stress
      inducible, stable solute accumulation appears to provide better protection under
      drought and salt-stress conditions than strategies using osmotic adjustment by
      metabolites that are constitutively present.

PMID- 12223868
TI  - Pollen-Stigma Adhesion in Kale Is Not Dependent on the Self-(In)Compatibility
      Genotype.
AB  - The adhesion of pollen on the stigmas of flowering plants is a critical step for
      the success of reproduction in angiosperms, long considered to present some
      specificity in terms of self-incompatibility. We carried out quantitative
      measurements of the pollen-stigma adhesion (expressed in Newtons) in kale
      (Brassica oleracea), using the flotation force of Archimedes exerted by dense
      sucrose solutions (50%, w/v) to release pollen grains fixed on the surface of
      stigmas. We demonstrate that pollen adhesion varies with the genotypes of the
      plants used as partners, but increases with time in all cases for about 30 to 60
      min after pollination. There is no correlation with the self- or cross-status of
      the pollinations, nor with the self-compatible or -incompatible genotypes of the
      parents. Only late events of pollination, after the germination or arrest of the
      pollen tube, depend on compatibility type. Biochemical and physiological
      dissection of pollen-stigma adhesion points to major components of this
      interaction: among male components, the pollen coating, eliminated by
      delipidation (or modified by mutation in the case of the cer mutants of the
      related species Arabidopsis thaliana), plays a major role in adhesion; the
      genetic background of the pollen parent is also of some importance. On the female
      side, the developmental stage of the stigma and the protein constituents of the
      stigmatic pellicle are critical for pollen capture. The SLG and SLR1 proteins are
      not involved in the initial stages of pollen adhesion on the stigma but one or
      both may be involved in the later stages.

PMID- 12223869
TI  - SO42- Deprivation Has an Early Effect on the Content of Ribulose-1,5-Bisphosphate
      Carboxylase/Oxygenase and Photosynthesis in Young Leaves of Wheat.
AB  - Wheat (Triticum aestivum cv Chinese Spring) supplied with 0.45 mM SO42- for 14 d
      with relative growth rates (RGR) of 0.22 to 0.24 d-1 was deprived of S for 7 to 8
      d. There was no significant effect on RGR or leaf development (leaf 2 length was
      constant; leaf 3 expanded for 2-4 d; leaf 4 emerged and elongated throughout the
      experiment) during the S deprivation. In controls the net assimilation rate (A)
      closely reflected leaf ontogeny. S deprivation affected A in all leaves,
      particularly leaf 4, in which A remained at 8 to 10 [mu]mol CO2 m-2 s-1, whereas
      in controls A rose steadily to >20 [mu]mol CO2 m-2 s-1. In leaf 2, with a fully
      assembled photosynthetic system, A decreased in S-deprived plants relative to
      controls only at the end of the experiment. Effects on A were not due to altered
      stomatal conductance or leaf internal [CO2] ([C]i); decreases in the initial
      slope of A/[C]i curves indicated an effect of S deprivation on the carboxylase
      efficiency. Measurement of Rubisco activity and large subunit protein abundance
      paralleled effects on A and A/[C]i in S-deprived leaves. Negative effects on
      photosynthesis in S-deprived plants are discussed in relation to mobilization of
      S reserves, including Rubisco, emphasizing the need for continuous S supply
      during vegetative growth.

PMID- 12223870
TI  - Characterization of Blue Light Signal Transduction Chains That Control
      Development and Maintenance of Sexual Competence in Chlamydomonas reinhardtii.
AB  - Blue light induces the differentiation of Chlamydomonas reinhardtii pregametes to
      gametes. The light-induced conversion of pregametes to gametes is protein
      synthesis dependent and proceeds only after a lag phase. Upon incubation in the
      dark, gametes lost their mating ability, resulting in dark-inactivated gametes.
      Reillumination rapidly restored mating competence and this was shown to be
      independent of protein synthesis. Apparently, differentiation and maintenance of
      gametic competence are both regulated by light. Whether one or two light
      activated signal pathways are involved was investigated using pharmacological
      compounds that affect signal transduction. Compounds that affected pregamete-to
      gamete conversion affected the expression of a gamete-specific gene in a similar
      fashion. Other drugs affected only dark-inactivated gametes, suggesting that
      reactivating gametes requires a separate signaling pathway. Combined treatments
      provided evidence for the consecutive action of a phosphatase and a protein
      kinase C-like kinase in the light-induced reactivation process.

PMID- 12223871
TI  - Root-Zone Salinity Alters Raffinose Oligosaccharide Metabolism and Transport in
      Coleus.
AB  - Exposure of variegated coleus (Coleus blumei Benth.) plants to a saline root-zone
      environment (60 mM NaCl:12 mM CaCl2) resulted in a significant decline in
      elongation growth rate over the 30-d experimental period. During the initial 5 to
      10 d of exposure, mature source leaves showed strongly diminished rates of
      photosynthesis, which gradually recovered to close to the control rates by the
      end of the experiment. In green leaf tissues, starch levels showed the same
      transient decline and recovery pattern. Low starch levels were accompanied by the
      appearance of several novel carbohydrates, including high-molecular-weight
      raffinose family oligosaccharides (RFOs) with a degree of polymerization (DP) of
      5 to 8, and an O-methylated inositol (OMI). New enzyme activities, including
      galactan:galactan galactosyltransferase, for the synthesis of high-DP RFOs and
      myo-inositol 6-O-methyltransferase for O-methylation of myo-inositol, were
      induced by salinity stress. Phloem-sap analysis showed that in the stressed
      condition substantially more sucrose than RFO was exported, as was the OMI. In
      white sink tissues these phloem sugars were used to synthesize high-DP RFOs but
      not OMIs. In sink tissues galactan:galactan galactosyltransferase but not myo
      inositol 6-O-methyltransferase was induced by salinity stress. Models reflecting
      the changes in carbohydrate metabolism in source and sink tissues in response to
      salinity stress are presented.

PMID- 12223872
TI  - Evidence for Chewing Insect-Specific Molecular Events Distinct from a General
      Wound Response in Leaves.
AB  - The timing of transcript accumulation of several wound-induced genes is different
      in insect-damaged and mechanically damaged leaves. Transcripts for the proteinase
      inhibitor II and 3-hydroxy-3-methylglutaryl-coenzyme A reductase genes accumulate
      more rapidly in potato (Solanum tuberosum L.) leaves chewed on by caterpillars
      than in leaves damaged mechanically. The timing of maximum transcript
      accumulation was not affected by the degree of damage inflicted by the insect
      larvae. When applied to a mechanical wound site, regurgitant isolated from
      Manduca sexta larvae causes transcript accumulation profiles to shift to parallel
      those in insect-damaged tissue. Whether obtained from larvae fed either potato
      leaves or a nonplant diet, insect regurgitant fed through the petiole of detached
      leaves also induces accumulation of these transcripts. The transcript
      accumulation-inducing activity of regurgitant is enhanced by heating at
      100[deg]C. Our data suggest that a heat-stable, insect-derived elicitor functions
      to induce the rapid accumulation of transcripts that may be involved in plant
      defense against herbivores. Distinct signal transduction pathways that can
      distinguish between insect damage and abiotic damage might therefore exist in
      plants.

PMID- 12223873
TI  - Flavonoid-Peroxidase Reaction as a Detoxification Mechanism of Plant Cells
      against H2O2.
AB  - Recent studies have revealed that dietary flavonoids are potent radical
      scavengers, acting in a manner similar to ascorbate and [alpha]-tocopherol.
      However, it is still not clear whether flavonoids have a similar antioxidative
      function in plants. We examined the possibility that flavonoids could function as
      stress protectants in plant cells by scavenging H2O2. Two major flavonoids,
      quercetin and kaempferol glycosides, were isolated from leaves of the tropical
      tree Schefflera arboricola Hayata. Both glycosides and aglycones of isolated
      flavonols were oxidized by H2O2 in the presence of horse-radish peroxidase and/or
      in a soluble fraction of S. arboricola leaf extract. The rates of oxidation were
      in the order quercetin > kaempferol > quercetin glycoside >> kaempferol
      glycoside. Judging from the effects of inhibitors such as KCN, p
      chloromercuribenzoate, and 3-amino-1H-1,2,4-triazole, we conclude that guaiacol
      peroxidase in the soluble fraction catalyzes H2O2-dependent oxidation of
      flavonols. In the flavonol-guaiacol peroxidase reaction, ascorbate had the
      potential to regenerate flavonols by reducing the oxidized product. These results
      provide further evidence that the flavonoid-peroxidase reaction can function as a
      mechanism for H2O2 scavenging in plants.

PMID- 12223874
TI  - Isoprene Increases Thermotolerance of Isoprene-Emitting Species.
AB  - Isoprene-emitting plants lose a large portion of their assimilated C as isoprene.
      Because isoprene synthesis can be regulated, it has been assumed that isoprene
      benefits the plant. Since the rate of isoprene emission from leaves is highly
      responsive to temperature, we hypothesized that isoprene benefits plants by
      increasing their thermotolerance. We used three methods to measure
      isopreneinduced thermotolerance in leaves. Each technique assayed thermotolerance
      under conditions that suppressed endogenous isoprene synthesis. When measured by
      chlorophyll fluorescence, thermotolerance of kudzu (Pueraria lobata [Willd.]
      Ohwi.) leaves increased as much as 4[deg]C in very low light. With higher light,
      isoprene increased thermotolerance of kudzu leaves by as much as 10[deg]C. When
      measured as the temperature at which photosynthesis declined to zero,
      thermotolerance increased with added isoprene by 2.5[deg]C. All three measures of
      thermotolerance were dose dependent. Both fluorescence techniques also showed
      isoprene-induced thermotolerance in white oak (Quercus alba L.). Thermotolerance
      was not observed in bean (Phaseolus vulgaris var Linden), a species that does not
      emit isoprene. None of the experiments was designed to determine the mechanism of
      thermotolerance, but we theorize that isoprene functions by enhancing hydrophobic
      interactions in membranes.

PMID- 12223876
TI  - Evidence from Polygene Mapping for a Causal Relationship between Potato Tuber
      Dormancy and Abscisic Acid Content.
AB  - In previous studies polygene mapping of a backcross population derived from
      haploid potato (Solanum tuberosum) and a diploid wild species (Solanum
      berthaultii) showed at least eight quantitative trait loci (QTLs) associated with
      tuber dormancy. The same population was mapped for abscisic acid (ABA) content in
      tubers so that any QTLs identified could be compared with those detected
      previously. At least three distinct loci on three chromosomes (2, 4, and 7) were
      associated with variation in ABA content. One of the QTLs was detected only as a
      main (single locus) effect, and two QTLs were found through two-locus interaction
      analysis (epistasis). Interaction between QTLs at markers TG234 (chromosome 2)
      and TG155 (chromosome 4) explained 20% of total phenotypic variance for this
      trait. The interaction closely resembled one previously detected for dormancy,
      suggesting an association between high ABA content and long tuber dormancy.
      Although relationships between ABA level and dormancy could be demonstrated
      through polygene mapping, there was no indication of a relationship between these
      traits when they were subjected to a conventional correlation test. This
      illustrates the usefulness of polygene mapping as a tool to identify possible
      associations between hormone levels and plant development.

PMID- 12223875
TI  - Constitutively Elevated Levels of Putrescine and Putrescine-Generating Enzymes
      Correlated with Oxidant Stress Resistance in Conyza bonariensis and Wheat.
AB  - Oxidant stress resistance in Conyza bonariensis and wheat (Triticum aestivum) has
      been correlated with high levels of antioxidant enzyme activities. Additionally,
      external oxidant stresses can increase a plant's levels of the enzymes of
      polyamine biosynthesis and polyamines, especially putrescine. We investigated the
      constitutive relationships between putrescine, putrescine-generating enzymes, and
      oxidant stress resistance in wheat and C. bonariensis. Putrescine was
      Constitutively elevated (2.5- to 5.7-fold) in 2-week-old-resistant wheat and C.
      bonariensis biotypes, which correlated with a 10- to 15-fold increase in paraquat
      oxidant resistance. Arginine and ornithine decarboxylase activities doubled,
      along with higher putrescine levels in resistant C. bonariensis. The variations
      in levels of putrescine and arginine and ornithine decarboxylase activities
      paralleled the constitutive variation of antioxidant enzymes, as well as oxidant
      resistance. Higher levels of both putrescine and antioxidant enzyme activities
      occurred during a peak of oxidant resistance at 10 weeks, when paraquat
      resistance in C. bonariensis plants is >50-fold greater than in the sensitive
      biotype. Application of 100 [mu]M putrescine can double oxidant-stress resistance
      in the resistant C. bonariensis. Putrescine may play an important role in
      contributing to the base level of oxidant resistance found at the nonpeak period.

PMID- 12223877
TI  - Sugar-Starvation-Induced Changes of Carbon Metabolism in Excised Maize Root Tips.
AB  - Excised maize (Zea mays L.) root tips were used to study the early metabolic
      effects of glucose (Glc) starvation. Root tips were prelabeled with [1-13C]Glc so
      that carbohydrates and metabolic intermediates were close to steady-state
      labeling, but lipids and proteins were scarcely labeled. They were then incubated
      in a sugar-deprived medium for carbon starvation. Changes in the level of soluble
      sugars, the respiratory quotient, and the 13C enrichment of intermediates, as
      measured by 13C and 1H nuclear magnetic resonance, were studied to detect changes
      in carbon fluxes through glycolysis and the tricarboxylic acid cycle. Labeling of
      glutamate carbons revealed two major changes in carbon input into the
      tricarboxylic acid cycle: (a) the phosphoenolpyruvate carboxylase flux stopped
      early after the start of Glc starvation, and (b) the contribution of glycolysis
      as the source of acetyl-coenzyme A for respiration decreased progressively,
      indicating an increasing contribution of the catabolism of protein amino acids,
      fatty acids, or both. The enrichment of glutamate carbons gave no evidence for
      proteolysis in the early steps of starvation, indicating that the catabolism of
      proteins was delayed compared with that of fatty acids. Labeling of carbohydrates
      showed that sucrose turnover continues during sugar starvation, but gave no
      indication for any significant flux through gluconeogenesis.

PMID- 12223878
TI  - Visualization of Freezing Behaviors in Leaf and Flower Buds of Full-Moon Maple by
      Nuclear Magnetic Resonance Microscopy.
AB  - 1H-Nuclear magnetic resonance (NMR) microscopy was used to study the freezing
      behavior of wintering buds of full-moon maple (Acer japonicum Thunb.). The images
      obtained predominantly reflected the density of mobile (i.e. non-ice) protons
      from unfrozen water. A comparison of NMR images taken at different subfreezing
      temperatures revealed which tissues produced high- and low-temperature exotherms
      in differential thermal analyses. In leaf and lower buds of A. japonicum, the
      scales and stem bark tissues were already frozen by -7[deg]C, but the primordial
      inflorescence and terminal primordial shoots remained supercooled at -14[deg]C,
      and the lateral primordial shoots were unfrozen even at -21[deg]C. The freezing
      of these supercooled tissues was associated with their loss of viability. The
      size of the supercooled primordial shoots and inflorescences was gradually
      reduced with decreasing temperature, indicating extraorgan freezing in these
      tissues. During this process the formation of dark regions beneath the primordia
      and subsequent gradual darkening in the basal part of supercooled primordia were
      visible. As the lateral shoot primordia were cooled, the unfrozen area was
      considerably reduced. Since the lateral primordia remained viable down to 
      40[deg]C, with no detectable low-temperature exotherms, they probably underwent
      type I extraorgan freezing. Deep supercooling in the xylem was clearly imaged.
      NMR microscopy is a powerful tool for noninvasively visualizing harmonized
      freezing behaviors in complex plant organs.

PMID- 12223879
TI  - S-Methylmethionine Conversion to Dimethylsulfoniopropionate: Evidence for an
      Unusual Transamination Reaction.
AB  - Leaves of Wollastonia biflora (L.) DC. synthesize the osmoprotectant 3
      dimethylsulfoniopropionate (DMSP) from methionine via S-methylmethionine (SMM)
      and 3-dimethylsulfoniopropionaldehyde (DMSP-ald); no other intermediates have
      been detected. To test whether the amino group of SMM is lost by transamination
      or deamination, [methyl-2H3,15N]SMM was supplied to leaf discs, and 15N-labeling
      of amino acids was monitored, along with synthesis of [2H3]DMSP. After short
      incubations more 15N was incorporated into glutamate than into other amino acids,
      and the 15N abundance in glutamate exceeded that in the amide group of glutamine
      (Gln). This is more consistent with transamination than deamination, because
      deamination would be predicted to give greater labeling of Gln amide N due to
      reassimilation, via Gln synthetase, of the 15NH4+ released. This prediction was
      borne out by control experiments with 15NH4Cl. The transamination product of SMM,
      4-dimethylsulfonio-2-oxobutyrate (DMSOB), is expected to be extremely unstable.
      This was confirmed by attempting to synthesize it enzymatically from SMM using L
      amino acid oxidase or Gln transaminase K and from 4-methylthio-2-oxobutyrate
      using methionine S-methyltransferase. In each case, the reaction product
      decomposed rapidly, releasing dimethylsulfide. The conversion of SMM to DMSP-ald
      is therefore unlikely to involve a simple transamination that generates free
      DMSOB. Plausible alternatives are that DMSOB is channeled within a specialized
      transaminase-decarboxylase complex or that it exists only as the bound
      intermediate of a single enzyme catalyzing an unusual transamination
      decarboxylation reaction.

PMID- 12223880
TI  - Modification of Sulfhydryl Groups in the [gamma]-Subunit of Chloroplast-Coupling
      Factor 1 Affects the Proton Slip through the ATP Synthase.
AB  - A large proton leak not coupled to ATP synthesis (slip) occurs at alkaline pH
      through the chloroplast ATP synthase (Y. Evron, M. Avron [1990] Biochim Biophys
      Acta 1019: 115-120). The involvement of the ATP synthase [gamma]-subunit in the
      regulation of proton conductance was analyzed by measuring the effect of
      thiolalkylating agents on proton slip. Alkylation by N-ethylmaleimide of [gamma]
      cysteine (Cys)-89, which is exposed upon energization of thylakoids, increases
      the slip only at alkaline pH. The slip is partially suppressed by low
      concentrations of adenine nucleotides and is completely eliminated by
      venturicidin, a blocker of the hydrophobic polypeptide complex of the chloroplast
      ATP synthase (CF0). Conversely, cross-linking of [gamma]-Cys-89 with [gamma]-Cys
      322 renders the ATP synthase leaky to protons and insensitive to ATP also at
      neutral pH. The accessibility of [gamma]-Cys-89 to alkylation by fluorescein
      maleimide is completely suppressed by N,N-dicyclohexylcarbodiimide and by
      venturicidin, which block proton conductance through CF0 and increase the pH
      gradient. These results suggest that the [gamma]-subunit has a dominant role in
      proton gating through the ATP synthase and responds to changes in pH and ligands
      taking place on either side of the thylakoid membrane. It is proposed that the
      conformational changes that induce the proton slip and the exposure of [gamma]
      Cys-89 reflect the conversion of the enzyme from a catalytically latent to an
      active state, and depend on the deprotonation of a stromal site at alkaline pH
      and on protonation of an intrathylakoid inner site upon energization. Therefore,
      conditions that induce the conformational activation also provide the driving
      force for ATP synthesis.

PMID- 12223881
TI  - Regulation of Triacylglucose Fatty Acid Composition (Uridine Diphosphate
      Glucose:Fatty Acid Glucosyltransferases with Overlapping Chain-Length
      Specificity).
AB  - UDP-glucose (UDP-Glc):fatty acid glucosyltransferases catalyze the UDP-Glc
      dependent activation of fatty acids as 1-O-acyl-[beta]-glucoses. 1-O-Acyl-[beta]
      glucoses act as acyl donors in the biosynthesis of 2,3,4-tri-O-acylglucoses
      secreted by wild tomato (Lycopersicon pennellii) glandular trichomes. The acyl
      composition of L. pennellii 2,3,4-tri-O-acylglucoses is dominated by branched
      short-chain acids (4:0 and 5:0; approximately 65%) and straight and branched
      medium-chain-length fatty acids (10:0 and 12:0; approximately 35%). Two
      operationally soluble UDP-Glc:fatty acid glucosyltransferases (I and II) were
      separated and partially purified from L. pennellii (LA1376) leaves by
      polyethylene glycol precipitation followed by DEAE-Sepharose and Cibacron Blue
      3GA-agarose chromatography. Whereas both transferases possessed similar affinity
      for UDP-Glc, glucosyltransferase I showed higher specificity toward short-chain
      fatty acids (4:0) and glucosyltransferase II showed higher specificity toward
      medium-chain fatty acids (8:0 and 12:0). The overlapping specificity of UDP
      Glc:fatty acid glucosyltransferases for 4:0 to 12:0 fatty acid chain lengths
      suggests that the mechanism of 6:0 to 9:0 exclusion from acyl substituents of
      2,3,4-tri-O-acylglucoses is unlikely to be controlled at the level of fatty acid
      activation. UDP-Glc:fatty acid glucosyltransferases are also present in
      cultivated tomato (Lycopersicon esculentum), and activities toward 4:0, 8:0, and
      12:0 fatty acids do not appear to be primarily epidermal when assayed in
      interspecific periclinal chimeras.

PMID- 12223882
TI  - Enzymes of the Primary Phosphatidylethanolamine Biosynthetic Pathway in
      Postgermination Castor Bean Endosperm (Developmental Profiles and Partial
      Purification of the Mitochondrial CTP:Ethanolaminephosphate
      Cytidylyltransferase).
AB  - Ethanolamine kinase, CTP:ethanolaminephosphate cytidylyltransferase (ECT), and
      ethanolaminephosphotransferase, which sequentially catalyze the primary pathway
      for phosphatidylethanolamine synthesis, were measured in castor bean (Ricinus
      communis L. var Hale) endosperm for 6 d after the onset of imbibition.
      Ethanolamine kinase (EC 2.7.1.82) activity was cytosolic, increasing slowly
      during the first 5 d and then declining. Total ECT (EC 2.7.7.14) activity
      increased until the 4th d, but the endoplasmic reticulum fraction of the activity
      peaked at d 3, and the mitochondrial activity peaked at d 4.
      Diacylglycerol:CDPethanolamine ethanolaminephosphotransferase (EC 2.7.8.1)
      increased during the first 2 d after imbibition began, after which it declined.
      The lowest activity of ethanolamine kinase during postgermination was more than 5
      fold higher than the maximum activity of ECT, and the total activity of
      diacylglycerol:CDPethanolamine ethanolaminephosphotransferase at d 2 was at least
      triple that of ECT of the endoplasmic reticulum. We have partially purified ECT
      from mitochondrial fractions of postgermination castor bean endosperm starting
      with mitochondria purified by sucrose (Suc) density gradient centrifugation and
      broken by osmotic shock and homogenization. The membrane-bound ECT was
      solubilized with 1.5% 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1
      propanesulfonate and purified approximately 118-fold by polyethylene glycol
      precipitation, chromatography on Sephacryl S-200, and then Suc gradient
      centrifugation. The continuous presence of both salt (0.5 M NaCl) and detergent
      (1% [w/v] 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate)
      was necessary to prevent aggregation. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis of the final activity peak resulted in a prominent protein band
      at 35 kD, which correlated with bands from peak ECT activity fractions after both
      Suc gradient centrifugation and gel filtration on Sephacryl S-200. The activity
      of this enzyme was enhanced by the addition of several phospholipids.

PMID- 12223883
TI  - Phloem-Specific Expression of the Tobacco Mosaic Virus Movement Protein Alters
      Carbon Metabolism and Partitioning in Transgenic Potato Plants.
AB  - The tobacco mosaic virus movement protein (TMV-MP) has pleiotropic effects when
      expressed in transgenic tobacco (Nicotiana tabacum) plants. In addition to its
      ability to increase the plasmodesmal size-exclusion limit, the TMV-MP alters
      carbohydrate metabolism in source leaves and dry matter partitioning between the
      various plant organs. In the present study the TMV-MP was expressed under the
      control of a phloem-specific promoter (rolC), and this system was employed to
      further explore the potential sites at which the TMV-MP exerts its influence over
      carbon metabolism and transport in transgenic potato (Solanum tuberosum) plants.
      Immunohistochemical analyses indicated that the TMV-MP was localized mainly to
      phloem parenchyma and companion cells. Starch and sucrose accumulated in source
      leaves of these plants to significantly higher levels compared with control
      potato lines. In addition, the rate of sucrose efflux from excised petioles was
      lower compared with control plants. Furthermore, under short-day conditions,
      carbon partitioning was lower to the roots and higher to tubers in rolC plants
      compared with controls. These results are discussed in terms of the mode(s) by
      which the TMV-MP exerts its influence over carbon metabolism and photoassimilate
      translocation.

PMID- 12223884
TI  - Dynamics of Xanthophyll-Cycle Activity in Different Antenna Subcomplexes in the
      Photosynthetic Membranes of Higher Plants (The Relationship between Zeaxanthin
      Conversion and Nonphotochemical Fluorescence Quenching).
AB  - The generation of nonphotochemical quenching of chlorophyll fluorescence (qN) in
      the antenna of photosystem II (PSII) is accompanied by the de-epoxidation of
      violaxanthin to antheraxanthin and zeaxanthin. The function of zeaxanthin in two
      mechanisms of qN, energy-dependent quenching (qE) and photoinhibitory quenching
      (qI), was investigated by measuring the de-epoxidation state in the antenna
      subcomplexes of PSII during the generation and relaxation of qN under varying
      conditions. Three different antenna subcomplexes were separated by isoelectric
      focusing: Lhcb1/2/3, Lhcb5/6, and the Lhcb4/PSII core. Under all conditions, the
      highest de-epoxidation state was detected in Lhcb1/2/3 and Lhcb5/6. The kinetics
      of de-epoxidation in these complexes were found to be similar to the formation of
      qE. The Lhcb4/PSII core showed the most pronounced differences in the de
      epoxidation state when illumination with low and high light intensities was
      compared, correlating roughly with the differences in qI. Furthermore, the
      epoxidation kinetics in the Lhcb4/PSII core showed the most pronounced
      differences of all subcomplexes when comparing the epoxidation after either
      moderate or very strong photoinhibitory preillumination. Our data support the
      suggestion that zeaxanthin formation/epoxidation in Lhcb1-3 and Lhcb5/6 may be
      related to qE, and in Lhcb4 (and/or PSII core) to qI.

PMID- 12223885
TI  - The Role of Metal Transport and Tolerance in Nickel Hyperaccumulation by Thlaspi
      goesingense Halacsy.
AB  - Metal hyperaccumulators are plants that are capable of extracting metals from the
      soil and accumulating them to extraordinary concentrations in aboveground tissues
      (greater than 0.1% dry biomass Ni or Co or greater than 1% dry biomass Zn or Mn).
      Approximately 400 hyperaccumulator species have been identified, according to the
      analysis of field-collected specimens. Metal hyperaccumulators are interesting
      model organisms to study for the development of a phytoremediation technology,
      the use of plants to remove pollutant metals from soils. However, little is known
      about the molecular, biochemical, and physiological processes that result in the
      hyperaccumulator phenotype. We investigated the role of Ni tolerance and
      transport in Ni hyperaccumulation by Thlaspi goesingense, using plant biomass
      production, evapotranspiration, and protoplast viability assays, and by following
      short- and long-term uptake of Ni into roots and shoots. As long as both species
      (T. goesingense and Thlaspi arvense) were unaffected by Ni toxicity, the rates of
      Ni translocation from roots to shoots were the same in both the hyper- and
      nonaccumulator species. Our data suggest that Ni tolerance is sufficient to
      explain the Ni hyperaccumulator phenotype observed in hydroponically cultured T.
      goesingense when compared with the Ni-sensitive nonhyperaccumulator T. arvense.

PMID- 12223886
TI  - Carbon Partitioning during Sucrose Accumulation in Sugarcane Internodal Tissue.
AB  - The temporal relationship between sucrose (Suc) accumulation and carbon
      partitioning was investigated in developing sugarcane internodes. Radiolabeling
      studies on tissue slices, which contained Suc concentrations ranging from 14 to
      42% of the dry mass, indicated that maturation coincided with a redirection of
      carbon from water-insoluble matter, respiration, amino acids, organic acids, and
      phosphorylated intermediates into Suc. It is evident that a cycle of Suc
      synthesis and degradation exists in all of the internodes. The decreased
      allocation of carbon to respiration coincides with a decreased flux from the
      hexose pool. Both the glucose and fructose (Fru) concentrations significantly
      decrease during maturation. The phosphoenolpyruvate, Fru-6-phosphate (Fru-6-P),
      and Fru-2,6-bisphosphate (Fru-2, 6-P2) concentrations decrease between the young
      and older internodal tissue, whereas the inorganic phosphate concentration
      increases. The calculated mass-action ratios indicate that the ATP-dependent
      phosphofructokinase, pyruvate kinase, and Fru-1,6-bisphosphatase reactions are
      tightly regulated in all of the internodes, and no evidence was found that major
      changes in the regulation of any of these enzymes occur. The pyrophosphate
      dependent phosphofructokinase reaction is in apparent equilibrium in all the
      internodes. Substrate availability might be one of the prime factors contributing
      to the observed decrease in respiration.

PMID- 12223887
TI  - Effect of Nitrogen Nutrition on Remobilization of Protein Sulfur in the Leaves of
      Vegetative Soybean and Associated Changes in Soluble Sulfur Metabolites.
AB  - The hypothesis that protein S is remobilized from mature leaves in response to N
      stress but not S stress was examined by transferring vegetative soybean (Glycine
      max L. Merr) plants grown with adequate sulfate and nitrate to nutrient medium
      with low sulfate (5 [mu]M) and nitrate at either 15, 7.5, 2, or 0.25 mM. Soluble
      S decreased to very low levels in mature and maturing leaves, especially in low-N
      plants. At high [N], insoluble S (protein) in mature leaves remained constant,
      but at low [N], after the soluble S declined, up to 40% of the insoluble S was
      exported. The losses were complemented by gains, initially in soluble S, but
      subsequently in insoluble S, in the expanding leaves and the root. In low-N
      plants, but not in high-N plants, the decrease in insoluble S in mature leaves
      was complemented by increases in homoglutathione (hGSH), Cys, and Met. At low
      [N], but not at high [N], the developing leaf, leaf 5, contained high amounts of
      soluble S, mostly hGSH. The results suggest that, at low [N], protein S is
      metabolized to hGSH, which serves as the principal transport compound for the
      export of organic S.

PMID- 12223888
TI  - Regulation and Localization of Key Enzymes during the Induction of Kranz-Less, C4
      Type Photosynthesis in Hydrilla verticillata.
AB  - Kranz-less, C4-type photosynthesis was induced in the submersed monocot Hydrilla
      verticillata (L.f.) Royle. During a 12-d induction period the CO2 compensation
      point and O2 inhibition of photosynthesis declined linearly. Phosphoenolpyruvate
      carboxylase (PEPC) activity increased 16-fold, with the major increase occurring
      within 3 d. Asparagine and alanine aminotransferases were also induced rapidly.
      Pyruvate orthophosphate dikinase (PPDK) and NADP-malic enzyme (ME) activities
      increased 10-fold but slowly over 15 d. Total ribulose-1,5-bisphosphate
      carboxylase/oxygenase activity did not increase, and its activation declined from
      82 to 50%. Western blots for PEPC, PPDK, and NADP-ME indicated that increased
      protein levels were involved in their induction. The H. verticillata NADP-ME
      polypeptide was larger (90 kD) than the maize C4 enzyme (62 kD). PEPC and PPDK
      exhibited up-regulation in the light. Subcellular fractionation of C4-type leaves
      showed that PEPC was cytosolic, whereas PPDK and NADP-ME were located in the
      chloroplasts. The O2 inhibition of photosynthesis was doubled when C4-type but
      not C3-type leaves were exposed to diethyl oxalacetate, a PEPC inhibitor. The
      data are consistent with a C4-cycle concentrating CO2 in H. verticillata
      chloroplasts and indicate that Kranz anatomy is not obligatory for C4-type
      photosynthesis. H. verticillata predates modern terrestrial C4 monocots;
      therefore, this inducible CO2-concentrating mechanism may represent an ancient
      form of C4 photosynthesis.

PMID- 12223889
TI  - Properties of Two Outward-Rectifying Channels in Root Xylem Parenchyma Cells
      Suggest a Role in K+ Homeostasis and Long-Distance Signaling.
AB  - Xylem parenchyma cells (XPCs) control the composition of the transpiration stream
      in plants and are thought to play a role in long-distance signaling as well. We
      addressed the regulation, selectivity, and dependence on the apoplastic ion
      concentrations of two types of outward rectifiers in the plasma membrane of XPCs,
      to assess the physiological role of these conductances. In whole-cell recordings,
      the membrane conductance at depolarization was under the control of cytosolic
      Ca2+: at physiological Ca2+ levels (150 nM) the K+ outward-rectifying conductance
      (KORC) predominated, whereas at elevated Ca2+ levels (5 [mu]M), only the
      nonselective outward-rectifying conductance (NORC) was active. No such regulatory
      effect of Ca2+ was observed in inside-out experiments. The voltage dependence of
      whole-cell KORC currents strongly depended on apoplastic K+ concentration: an
      increase in apoplastic K+ resulted in a positive shift of the current-voltage
      curve, roughly following the shift in Nernst potential of K+. KORC is impermeable
      to Na+, but does translocate Ca2+ in addition to K+. In contrast to KORC, NORC
      selected poorly among monovalent cations and anions, the relative permeability
      PC+/PA- being about 1.9. Gating of NORC was largely unaffected by the level of K+
      in the bath. Under all ionic conditions tested, NORC tail currents or single
      channel currents reversed close to 0 mV. Using an in vivo xylem-perfusion
      technique, tetraethylammonium (an inhibitor of KORC) was shown to block K+
      transport to the shoot. These data support the hypothesis that release of K+ to
      the xylem sap is mediated by KORC. The molecular properties of these two
      conductances are discussed in the light of the distinct physiological role of
      XPCs.

PMID- 12223890
TI  - Enumeration, phenotyping, and identification of activation events in conjugates
      between T cells and antigen-presenting cells by flow cytometry.
AB  - Microscopic analysis of T cell-antigen-presenting cell (T cell:APC) interactions
      at the single cell level has been a powerful, but tedious and subjective,
      technique. In this paper, we describe a rapid and quantitative method to identify
      T cell:APC conjugates using succinimidyl ester dyes, which irreversibly label
      free amine groups on the cell surface. The labeled cell conjugates and subsequent
      activation events are detected by flow cytometry.

PMID- 12223891
TI  - A resident Golgi protein is excluded from peri-Golgi vesicles in NRK cells.
AB  - To understand the structure and the function of the Golgi apparatus, it is
      essential to establish how resident Golgi enzymes are localized in only a few
      Golgi cisternae. In particular it is crucial to establish whether Golgi enzymes
      are retained specifically in cisternae, or if they are continuously transported
      from cisterna to cisterna. Here we report that a resident Golgi enzyme is largely
      excluded from peri-Golgi transport vesicles in normal rat kidney cells, a cell
      type in which conflicting results have been reported. Analysis of the lateral
      distribution of two markers within Golgi cisternae led to the same conclusion: a
      protein incorporated in vesicles (KDEL receptor) is concentrated at the rims of
      cisternae where vesicles form, while mannosidase II is not. These results suggest
      that localization of resident Golgi enzymes is achieved primarily by selective
      retention within cisternae and exclusion from transport vesicles. These
      observations cannot easily be reconciled with the vision of rapidly maturing
      Golgi cisternae as the principal means of intra-Golgi transport.

PMID- 12223910
TI  - [Diagnostic cardiovascular imaging: should we rise to the challenge or mourn its
      loss?].

PMID- 12223911
TI  - [Dosimetry: are radiodiagnostic personnel category A? Or should we impose
      operational dosimetry in radiodiagnosis services?].

PMID- 12223912
TI  - [Imaging of osteoarticular tuberculosis].
AB  - PURPOSE: and methods. To perform an illustrated and educational review of
      musculoskeletal tuberculosis. RESULTS: As the incidence of musculoskeletal
      tuberculosis still increases, a review appears justified. The following four main
      presentations are detailed and illustrated, by emphasizing the value of both CT
      and MR imaging: a) spine tuberculosis (~ 50%) commonly involves two adjacent
      vertebral bodies with usual large paravertebral abscesses. The following lesions
      are highly suggestive of tuberculosis: solitary vertebral involvement, solitary
      epidural abscess with or without erosive spondylitis; b) osteo-arthritis:
      peripherally located erosions at synovial insertions with gradual narrowing of
      the joint space are highly suggestive; c) osteomyelitis: unusual, may involve any
      bones; d) tenosynovitis and bursitis. CONCLUSION: Imaging studies are essential
      for diagnosis and to assess the extent of musculo-skeletal tuberculosis.

PMID- 12223914
TI  - [Dosimetry and bone densitometry: examples of LUNAR IQ and HOLOGIC 4500A].
AB  - Patient dosimetry related to two bone densitometer units from different
      manufacturers (LUNAR IQ and HOLOGIC 4500A) were evaluated using the parallel beam
      technique and thermoluminescence from Ca (SO4)/Dy. The radiation dose measured
      for a phantom of 18 cm in thickness was 0,11 mGy (+/- 0,004) at a maximum current
      of 3 mA for the LUNAR IQ unit in the high-resolution mode. The radiation dose is
      0,28 mGy (+/- 0,011) for the HOLOGIC 4500A unit used at 2,5 mA in the high
      resolution-mode. These results obtained by thermoluminescence of the Ca (SO4)/Dy
      are in favor of the LUNAR IQ unit. However, dosimetry must be weighted against
      image quality.

PMID- 12223913
TI  - [Lipomatous tumors of soft tissues in the extremities and the waist in adults].
AB  - Lipomatous tumors of the upper and lower extremities in adults are frequent and
      lipoma is the most common soft tissue tumor. Most have a typical appearance at
      imaging but presentation and management may vary based on the exact histological
      subtype. The purpose of this paper is to review the main clinical, radiological
      and histological features of the different benign and malignant lipomatous
      tumors.

PMID- 12223915
TI  - [Stereotactic 11-gauge directional vacuum-assisted breast biopsy: experience with
      249 patients].
AB  - PURPOSE: To assess the value of percutaneous vacuum-assisted core biopsy to
      improve the diagnosis of non palpable mammographic abnormalities. MATERIALS AND
      METHODS: A total of 252 core biopsies using an 11G Mammotome((R))were performed
      in 249 patients. Stereotactic localization was performed in the prone position on
      a dedicated digital Fischer table. RESULTS: Fifty-one, or 25%, of 200 clusters of
      microcalcifications corresponded to carcinomas: 126 benign lesions, 23 atypical
      hyperplasia and LCIS, 31 DCIS, 15 invasive ductal carcinomas, and 4 false
      negative biopsies. In these 4 last cases, surgery was performed because
      radiographs of the core biopsy showed no microcalcifications; carcinoma was
      confirmed at histology of the surgical specimen. Using the BI-RADS system, 7
      lesions were category 3, 175 lesions were category 4, and 18 lesions were
      category 5. From a total of 52 masses, 31 were benign lesions, 2 were borderline
      lesions, and 19 were invasive carcinomas. From these, 5 lesions were category 3,
      31 were category 4, and 16 were category 5. Diagnostic surgical biopsy was
      avoided in 161 cases (63%), in 152 cases for benign lesions including 151 lesions
      classified as category 4 lesions and in 9 cases for multifocal or recurrent
      malignant lesions. CONCLUSION: When technical pitfalls are avoided and when
      presence of microcalcifications in the core biopsy sample is verified, vacuum
      assisted core biopsy with Mammotome((R)) 11G provides accurate diagnosis of non
      palpable mammographic abnormalities.

PMID- 12223916
TI  - [Value of MR imaging of the fetal kidney].
AB  - Sonography is the imaging modality of choice for initial evaluation of the fetus.
      However, the role of MR imaging for fetal evaluation is expanding. Based on a
      review of seven cases, the role of MRI to further characterize renal
      abnormalities detected at US, especially hyperechoic kidneys, is demonstrated.

PMID- 12223917
TI  - [Endovascular embolization of a splenic aneurysm and of a false aneurysm of the
      splenic artery].
AB  - Splenic artery aneurysms, once considered rare entities are now being reported
      with increasing frequency. Rupture may be the presenting and only symptom and can
      be fatal. The authors present two cases of splenic aneurysms treated by
      endovascular embolization. The initial imaging work-up included sonography,
      angiography and helical computed tomography with multiplanar and 3D reformations.
      This enabled comprehensive evaluation of the aneurysms, including their
      configuration, essential for coil selection. Embolization was uneventful. Post
      embolization angiograms confirmed exclusion of the aneurysms. Follow-up CT at 9
      months showed complete thrombosis of the aneurysms and no evidence of pancreatic
      or splenic complication. Endovascular management for definitive treatment of
      splenic aneurysms is technically possible and should be considered.

PMID- 12223918
TI  - [CT guided neurolysis of the sphenopalatine ganglion for management of refractory
      trigeminal neuralgia].
AB  - The authors present the case of a patient with recurrent trigeminal neuralgia,
      refractory to medical treatment and ablation of the trigeminal ganglion, who
      underwent three separate CT guided injections for pterygopalatine ganglion
      ablation over a two year period. Ablation of the pterygopalatine ganglion may be
      an effective technique for pain management in patients suffering from atypical
      facial pain syndrome, cluster headache, or neuritis. The technique used for CT
      guided ablation using alcohol or radiofrequency is described. The advantages and
      pitfalls of this technique are reviewed.

PMID- 12223919
TI  - [Post traumatic intercostal lung herniation: a case report].
AB  - The authors report a case of post traumatic lung herniation in a 76 year old
      obese retired coalminer with chronic obstructive pulmonary disease. Lung
      herniation is a rare event. It is typically is iatrogenic or post traumatic and
      sometimes occurs after a delay of several months or years. CT is useful for
      diagnosis.

PMID- 12223920
TI  - [Hemangioma of the humerus: value of imaging].
AB  - Hemangioma is an uncommon bone neoplasm that usually affects the craniofacial
      bones and spine, accounting for less than 1% of all primary bone tumors. The
      authors report a case of isolated hemangioma involving the proximal humerus in a
      22-year-old man. Radiographically, the lesion was a well-defined osteolytic
      process with marginal sclerosis. The CT images demonstrated an osteolytic lesion
      with coarse trabecular pattern and partial cortical breakthrough. Magnetic
      resonance imaging showed a multilocular and hemorrhagic lesion with fluid-fluid
      level, that was suggestive of aneurysmal bone cyst.

PMID- 12223921
TI  - [Quid? Subocclusion of the small intestine by a duodenal-jejunal lipoma].

PMID- 12223923
TI  - [Neuroradiology].

PMID- 12223924
TI  - [Bone and joint pathology].

PMID- 12223925
TI  - [Obstetrics-gynecology].

PMID- 12223926
TI  - [Cardiac imaging].

PMID- 12223927
TI  - [Pediatric imaging].

PMID- 12223928
TI  - [Gastrointestinal imaging].

PMID- 12223929
TI  - [Thorax].

PMID- 12223931
TI  - [Diagnostic scanning].

PMID- 12223930
TI  - [United, we stood!].

PMID- 12223932
TI  - [MRI. Better than multi-slice CT].

PMID- 12223933
TI  - [State of the art in ultrasonography].

PMID- 12223934
TI  - [Nuclear medicine].

PMID- 12223935
TI  - [Large field data capture arrays].

PMID- 12223936
TI  - [PACS, imaging networks. and management of medical images].

PMID- 12223937
TI  - [Rotational vertebro-basilar insufficiency secondary to a fibrous band of the
      longus colli muscle: value of CT spiral angiography diagnosis].
AB  - A CASE REPORT: The authors report a case of rotational vertebro-basilar
      insufficiency causing "drop-attacks". To our knowledge, it is the first case of
      extraluminal vertebral artery compression caused by a fibrous band of the longus
      colli muscle, demonstrated by spiral computed tomographic angiography with volume
      rendering reformation.

PMID- 12223938
TI  - [Lipoblastoma of the buttock].
AB  - Lipoblastoma is an uncommon benign soft tissue tumor arising from embryonal
      mesenchymal cells. It occurs mostly during early childhood with a predilection
      for the extremities, trunk, head and neck. This tumor tends to spread locally and
      no metastatic potential has been reported. Complete surgical resection is
      mandatory to prevent local recurrence. MRI provides excellent presurgical
      delineation of the tumor and confirms its fatty nature. Histology demonstrates
      the presence of lipoblasts in different stages of maturation; cytogenetic
      evaluation often discloses chromosomal anomalies of tumoral cells. A case of
      lipoblastoma of the buttock in a 10 month infant associated with anomalies of
      chromosome 8 is reported.

PMID- 12223939
TI  - [Jejunal volvulus secondary to torsion of a pedunculated subserosal lipoma: CT
      diagnosis of a rare cause of bowel obstruction].
AB  - The authors report a case of a bowel obstruction secondary to jejunal volvulus in
      relation with the torsion of a large pedunculated subserosal lipoma. To our
      knowledge, no such case has ever been reported. The differential diagnosis of
      intra-abdominal fatty tumors and differential diagnosis of such tumors in
      association with small bowel obstruction will be discussed. Small bowel volvulus
      secondary to torsion of a subserosal lipoma should be considered when CT shows a
      large encapsulated fatty tumor in a patient with suggestion of mechanical small
      bowel obstruction.

PMID- 12223940
TI  - [A new case of abdominal pregnancy].
AB  - The authors report a case of abdominal pregnancy that reached term. This type of
      pregnancy is now rare except in developing countries due to lack of early
      diagnosis. Ultrasonography is useful to confirm a clinically suspected diagnosis.
      MRI is helpful to further characterize the relation between placental tissue and
      intra-abdominal organs. Prognosis for the fetus is usually poor, and risks to the
      mother are non-negligible. Management is typically surgical and placental
      resection is the main concern. In this case, surgical delivery of an otherwise
      normal appearing infant was performed.

PMID- 12223941
TI  - [Quid? Subacute apophyseal avulsion of the right anterior-inferior iliac spine].

PMID- 12223942
TI  - [Use of brimonidine 0.2% in treatment of glaucoma or ocular hypertony after
      poorly tolerated beta-blocker treatment].
AB  - This study intended to evaluate the advantages of brimonidine tartrate 0.2%
      (Alphagan((R))), a selective alpha-2 receptor agonist, relaying a poorly
      tolerated beta-blocker treatment. Effectiveness, as assessed by intraocular
      pressure, local and general tolerance of the treatment, and the quality of life
      of the patients included in the study, was compared for these two eye drops. This
      multicenter and prospective study, performed by 450 ophthalmologists, included
      807 adults presenting with glaucoma or ocular hypertony over 8 months. After a
      poorly tolerated beta-blocker treatment, which had started at least 6 months
      before, these patients received brimonidine over 8 weeks. At 3 successive visits,
      intraocular pressure, biomicroscopic examination results, and visual acuity were
      recorded. A quality-of-life questionnaire evaluating breathlessness, fatigue,
      depressive mood, loss of appetite, and satisfaction with the treatment was also
      given to patients. In the 731 patients observed in the study, the analysis
      concluded a statistically significant decrease in intraocular pressure (-2.5mmHg)
      and in the cardiovascular parameters during brimonidine treatment: blood pressure
      was reduced by 3mmHg and 1.1mmHg for systolic and diastolic pressure,
      respectively. The heart rate rose by 1.7 beats/min. The quality-of-life
      questionnaire revealed less breathlessness (-26%), fatigue (-24.9%), depressive
      mood (-19.3%), and better appetite (+8.2%). The feeling of satisfaction with the
      brimonidine treatment was significantly improved for 95 patients. However, 12% of
      all patients stopped their treatment because of adverse effects. Brimonidine
      improved the glaucomatous patients' quality of life, at least in some areas.
      Improved intraocular pressure could at least in part result from better
      compliance with the treatment. Brimonidine is an encouraging alternative after an
      unsatisfactory beta-blocker treatment.

PMID- 12223943
TI  - [Cornea donation consent by telephone].
AB  - BACKGROUND: The cornea donation process often runs into problems of obtaining
      family consent. A face-to-face interview is often not possible for logistical
      reasons. We carried out a prospective study on the effectiveness of telephone
      contact in obtaining donation consent. MATERIAL AND METHODS: Consent was obtained
      by a single, non medical, hospital coordinator. He contacted families selected on
      good staff-family relations during the patient's stay. If a face-to-face
      interview was not possible, a telephone interview was conducted using a
      standardized procedure. RESULTS: Over 21 months, 334 families were contacted,
      either in a face-to-face interview (142, 42.5%) or by telephone (192, 57.5%).
      Donation consent was obtained in 66.5% of cases, 106 times by telephone (47.7%)
      and 116 times in the face-to-face interview (52.3%). The acceptance rate was
      55.2% by telephone and 81.6% face to face (p<0.001). CONCLUSIONS: The telephone
      interview was an effective method for obtaining consent for cornea donation.
      Although the acceptance rate using this method is lower than the face-to-face
      interview, using the telephone should not be overlooked as this enabled
      procurement of nearly half the corneas in our hospital.

PMID- 12223944
TI  - [Carbohydrate-deficient glycoprotein syndrome and progression in
      electrophysiological results].
AB  - PURPOSE: To document the progression of clinical and electrophysiological
      abnormalities in an infant with carbohydrate-deficient glycoprotein syndrome type
      Ia (CDGS Ia) over a period of 5 years. PATIENT AND METHODS: A 12-month-old male
      underwent clinical ophthalmic and electrophysiological examination at the age of
      1, 2, and 6 years. Neurological examination, magnetic resonance imaging of the
      brain and a genetic study were also undertaken. RESULTS: Clinical examination
      revealed hypotonia and ataxia with a convergent squint, nystagmus, myopia with
      pontocerebellar hypoplasia on the MRI of the brain. The initial electroretinogram
      showed reduced amplitude of the scotopic and photopic b wave. At 3 years of age,
      biological and genetic evaluations confirmed the diagnosis of CDGS Ia. At 6 years
      of age, the electroretinogram was flat with a marked delay in psychomotor
      development. CONCLUSION: Carbohydrate-deficient glycoprotein syndrome type Ia is
      a recently described cause of progressive retinal degeneration and an
      electroretinogram should be taken in patients with psychomotor retardation of
      unknown etiology. In addition, strabismus associated with electrophysiological
      signs of anomaly should raise the possibility of CDGS Ia.

PMID- 12223945
TI  - [Fungal contamination detection in cornea preservation media].
AB  - PURPOSE: Fungi can cause major complications following corneal grafting. In this
      study we aimed to verify the efficiency of a fungal contamination detection
      protocol for human corneas in preservation before clinical use. MATERIALS AND
      METHODS: The 12 most frequently found species of fungi responsible for keratitis
      and endophthalmitis were inoculated to preservation medium used by most French
      eye banks. A protocol used by several centers, including a daily visual control,
      was followed in order to check that it showed the presence of all microorganisms,
      particularly slow-growing filamentous fungi. RESULTS: Every species was detected
      in a time from 2 to 4 days. CONCLUSION: This microbiological contamination
      detection protocol of detection for human corneas in organ culture at +31 degrees
      C, seems to effectively detect the main agents responsible for fungal
      contamination.

PMID- 12223946
TI  - [Phototherapeutic keratectomy for the treatment of Cogan's microcystic
      dystrophy].
AB  - PURPOSE: This retrospective study was designed to investigate the therapeutic
      potential of phototherapeutic keratectomy (PTK) for the treatment of map-dot
      fingerprint corneal dystrophy (MDFCD). PATIENTS AND METHODS: PTK was performed
      with the Excimed UV 200 and with the Nidek EC5000 on 38 patients (55 eyes). Mean
      patient age was 51 years (range, 28-86 years). The mean follow-up period was 19
      months (range, 8-54 months). The treatment goal for each patient was to improve
      vision (17 eyes), to heal recurrent corneal erosions (28 eyes) or both (10 eyes).
      RESULTS: In 13 of 17 eyes (76.47%) with reduction in visual acuity, best
      corrected visual acuity (BCVA) improved by two lines or more. In 36 eyes of 38
      (94.7%) with recurrent corneal erosions, there was no recurrence during the
      follow-up period. No decreased BCVA was noted. No recurrence of corneal
      dystrophic changes was seen in the ablation zone at the final follow-up. The mean
      hyperopic shift caused by tissue ablation was +O.55+/-1.35 after 1 year.
      CONCLUSION: Excimer laser PTK is a safe and effective outpatient treatment and
      should be used as initial treatment for MDFCD.

PMID- 12223947
TI  - [Therapeutic strategy in delayed postoperative endophtalmitis: a report on 15
      cases].
AB  - PURPOSE: To report the treatment strategies and visual acuity outcomes of chronic
      postoperative endophthalmitis. MATERIAL: and methods: The authors reviewed the
      records of 15 patients presenting 3 or more weeks after cataract surgery with
      intraocular inflammation and treated at Bicetre Hospital from 1992 to 1998. Group
      I included 6 consecutive patients treated with vitrectomy and intravitreal
      antibiotic injection (vancomycin and cefazolin). Group II included 9 consecutive
      patients treated with intravitreal antibiotic injection (vancomycin and
      ceftazidime) and irrigation of the capsular bag (vancomycin). The minimum follow
      up period was 1 year. RESULTS: In group I, 2 patients had recurrent inflammation.
      In these patients, the capsular bag and the intraocular implant were removed. In
      1 patient there was culture-proven Corynebacterium and in 1 patient a
      Staphylococcus epidermidis was found. Final visual acuity was 20/40 or better in
      5 patients and 20/100 in 1 patient. Visual acuity improved in all cases. In group
      II no recurrence was seen in the 12-20 months of follow-up. In 2 patients there
      was proven Staphylococcus epidermidis and in one patient Propionibacterium acnes
      was found. Final visual acuity was 20/40 or more in 3 patients, 20/100 or more in
      4 patients and less than 20/200 in 2 patients. Visual acuity improved in 8 cases.
      CONCLUSIONS: Intravitreal antibiotic injection with vitrectomy and intravitreal
      antibiotic injection with antibiotic irrigation of the capsular bag are both
      effective in the treatment of delayed chronic postoperative endophthalmitis;
      however, with the second approach, there is minimal surgical trauma and the
      intraocular implant is retained.

PMID- 12223948
TI  - [Comparison of latanoprost monotherapy with timolol-dorzolamide combination in
      patients with open-angle glaucoma or ocular hypertension].
AB  - PURPOSE: To compare the efficacy and safety of latanoprost monotherapy to
      dorzolamide combined with timolol from pooled data of five multicenter,
      randomized, 3-month, observer-masked trials with identical study design. METHODS:
      Patients who were on a beta-blocker or dual therapy where one agent was a beta
      blocker were eligible after a 2- to 4-week run-in period on timolol 0.5%, twice
      daily. Patients then either discontinued timolol treatment and received
      latanoprost monotherapy n=345) or continued on timolol and received dorzolamide
      add-on therapy (n=352). Data from these 697 patients were included in the meta
      analysis. RESULTS: From an overall baseline of 22.8mmHg, the mean IOP reduction
      was 4.8mmHg (21%) in latanoprost-treated patients and 4.1mmHg (18%) in timolol +
      dorzolamide-treated patients p<0.001). A reduction in diurnal IOP of >=20% was
      achieved in 54% of the latanoprost-treated patients compared with 44% of the
      timolol + dorzolamide-treated patients. There was no marked difference between
      the two groups in the incidence of ocular and systemic events. CONCLUSION: This
      meta-analysis provides further support that a switch to latanoprost monotherapy
      can be an alternative to combined treatment with timolol + dorzolamide.

PMID- 12223949
TI  - [Ocular toxicity of deferoxamine: description and analysis of three
      observations].
AB  - INTRODUCTION: Deferoxamine is a specific chelating agent of trivalent anions:
      iron ion and aluminum ion. The main prescriptions for this treatment are primary
      non-curable by blood letting hemochromatosis, secondary hemosiderosis, and
      aluminum intoxication associated with chronic kidney failure. Since the early
      1980s, ocular toxicity has been documented in several publications. OBSERVATIONS:
      We recorded three clinical observations of patients presenting symptoms of an
      ocular toxicity caused by deferoxamine. The prescription of this treatment
      related to the presence of secondary hemosiderosis (a case of primitive
      myelofibrosis and a case of chronic myelomonocytic leukemia treated by blood
      transfusion) and an aluminum intoxication affecting a patient with chronic kidney
      failure. All three patients presented a gradual loss of visual acuity. The
      following were predominantly observed at the fundus examination which showed
      pigmentary anomalies near the macula such as mottling and dispersion affecting
      the electrophysiological studies. The termination of the treatment did not result
      in an improvement in the symptomatology. DISCUSSION: Considering the latest
      literature on the subject, the indications as well as the pharmaceutical
      properties of deferoxamine, the ophthalmological symptoms of this intoxication,
      the additional investigations and the anatomicopathological analyses are
      restated, together with the current pathogenical hypothesis. CONCLUSION:
      Deferoxamine can cause ocular toxicity resulting in severe and permanent lesions
      of the retinal pigment epithelium. The occurrence of disorders of the fundus and
      visual acuity requires, before and during the treatment, regular ophthalmological
      monitoring combined with electrophysiological explorations. This allows early
      treatment of the hematological or kidney disorder.

PMID- 12223950
TI  - [Risk factors for secondary cataract: a case-control study with multivariate
      analysis].
AB  - AIM: A retrospective case-control study was initiated to determine the risk
      factors for the development of posterior capsule opacification. SUBJECTS AND
      METHODS: 100 cases of patients with secondary cataract treated by YAG laser
      capsulotomy were compared with 100 controls (patients who had cataract surgery
      not complicated with a secondary cataract). The posterior capsule was examined by
      the biomicroscope. A 1-to-1 matched case-control study was designed by
      stratifying inclusions on the basis of age, sex, and delay. We studied the risk
      factors related to the patient, the primary cataract, the surgical technique, the
      surgeon's skill, and intraoperative and postoperative complications. All the
      lenses were biconvex and all-PMMA with the same design. Statistical analysis was
      done in 3 steps: a univariate analysis, then a bivariate analysis using chi
      square and the Student tests and finally, we performed a multivariate analysis
      with a logistic regression. The significance level for type I error rate was
      fixed at 5%. RESULTS: The average age was 61.6 years. The mean delay was 32.7
      months for cases and 34.5 months for controls. The bivariate analysis identified
      nine risk factors: corneal opacities (p=0.031), absence of a posterior chamber
      lens p=10(- 4)), the can opener anterior capsulotomy (p=0.003), ciliary sulcus
      fixation of the lens p=0.030), a large optic diameter of 7mm p=10(- 5)) and
      (t=0.002), poor intraoperative pupillary dilatation (p=0.003), a less experienced
      surgeon (p=3.10(- 4)), postoperative inflammation (p=0.021), and persistence of
      residual cortical material (p=0.002). The multivariate analysis selected five
      principal factors: absence of a posterior chamber lens, an optic diameter of 7mm,
      poor intraoperative pupillary dilatation, a less skilled surgeon, and persistence
      of cortical material. CONCLUSION: This case-control study reveals some of the
      risk factors previously identified and may contribute to the determination of
      methods for prevention of secondary cataract. The new intraocular lenses and
      pharmacological agents would lead to better results.

PMID- 12223951
TI  - [Endovascular treatment of sinus dural fistulas using vein catheterism].
AB  - PURPOSE: We report two techniques for treatment of dural arteriovenous fistulas
      using femoral vein catheterism and direct surgery via the superior ophthalmic
      vein. We will attempt to show the advantages of these new techniques instead of
      using the arterial pathway, which is currently the reference procedure. SUBJECTS
      AND METHOD: Mrs G, 75 years old was sent by her ophthalmologist because of a
      suspected orbital tumor. Visual acuity: right eye: 3/10, exophthalmia, chemosis,
      with no thrill or murmur. The fundus examination was normal. The ultrasound exam
      with color Doppler imaging showed an arterialization of the superior ophthalmic
      vein compatible with an arteriovenous sinus dural fistula. Angio-MRI revealed a
      large left cavernous sinus, confirming the diagnosis. Considering the type of the
      fistula and the weak physical condition of the patient, we decided to attempt an
      endovascular embolization with coil placement, using femoral vein catheterism.
      Exophthalmia regressed within days. The fistula remains sealed 1 year after the
      procedure. Mr D, 40 years old, showed a similar clinical aspect of sinus dural
      fistula. We attempted an embolization with the femoral vein, which failed. We
      decided to embolize the cavernous sinus via the direct surgical pathway of the
      superior ophthalmic vein. Coils were placed and the fistula was sealed.
      CONCLUSION: These clinical cases show two less invasive alternatives giving
      better results than arterial embolization, the reference method (Brooks 1930;
      Spearmann 1964; Parkinson 1965), endovascular trapping, or surgery.

PMID- 12223952
TI  - [Case report of a severe corneoscleral burn caused by the phacoemulsification
      probe].
AB  - We report a case in which a severe corneoscleral burn occurred during the first
      seconds of a phacoemulsification procedure. The procedure, a superior temporal
      corneal limbus incision on the right eye, was carried out on a 79-year-old woman
      presenting a cataract with an average lens density, who had no other risk factors
      for complications. In spite of a mild nucleus density and routine
      phacoemulsification equipment (PULSAR - OPTIKON 2000) with resterilizable parts,
      a severe corneal injury occurred with tissue shrinkage around the surgical wound.
      It led to an immediate severe astigmatism which only partially decreased in the
      following 7 months. We discuss the mechanism which may bring about this type of
      injury and the likely cause in this case. We also describe the primary sign
      ("lens milk") indicating that the procedure should immediately be stopped, and
      finally we suggest methods to reduce the incidence of such so-called
      "phacoburns".

PMID- 12223953
TI  - [Olfactory esthesioneuroblastoma with an ophtalmological presentation: a case
      report].
AB  - Esthesioneuroblastoma (ENB) is a rare malignant tumor, which develops from the
      olfactory neuroepithelium and is one of the rarest tumors of the nasal cavity.
      Revelation by ocular signs is unusual. We report the original observation of a
      case of ENB of the olfactive placodes in a 28-year-old adult discovered during
      exophthalmia. The authors studied the clinical, radiological, pathological, and
      therapeutic aspects. ENB should not be forgotten in case of unilateral tumorous
      exophthalmia associating rhinological signs.

PMID- 12223954
TI  - [Vogt-Koyanagi-Harada syndrome in children].
AB  - INTRODUCTION: Uveitis in children accounts for 5% to 10% of all uveitis cases.
      Some causes such as Vogt-Koyanagi-Harada syndrome rarely affect young children.
      We report two cases. CASE REPORT: No.1: A 9-year-old girl was followed up for
      severe and chronic total uveitis. General fundus depigmentation with several
      white and yellowish rounded lesions in peripheral fundus suggested the diagnosis
      of Vogt-Koyanagi-Harada, which was confirmed by the development of areas of
      vitiligo in the lumbar region. The patient was treated with a bolus of
      corticosteroid therapy. No. 2: A 12-year-old girl had bilateral uveopapillitis
      and the clinical initial examination and laboratory evaluation failed to provide
      a diagnosis. The patient was also treated with a bolus of corticosteroid therapy
      and then high-dose oral prednisone. After several months, the patient's
      examination showed a sunset glow fundus with several white and yellowish rounded
      lesions in peripheral fundus. DISCUSSION: Vogt-Koyanagi-Harada syndrome rarely
      affects young children, so the diagnosis may be difficult if the extraocular
      manifestations are not present. The bolus of corticosteroid therapy and cytotoxic
      agents may be necessary and the prognosis may be poor in severe cases.

PMID- 12223955
TI  - [Ocular hypertension and glaucoma: the contribution of large studies to daily
      practice].
AB  - Official guidelines to manage and treat various clinical presentations of
      glaucoma and ocular hypertension are not currently in wide use. Several well
      designed clinical trials have been published recently which can provide
      ophthalmologists with therapeutic recommendations. In the field of ocular
      hypertension, three major and historic studies are reported and discussed in this
      review. A more recent study undertaken in Sweden and the design of the Ocular
      Hypertension Treatment Study (OHTS) are reviewed as well, although the final
      results of this important trial have not yet been published. The conclusions of
      the Collaborative Normal Tension Study Group (CNTSG) have been expected for a
      long time since this disease is difficult to manage; a 30% reduction in baseline
      intraocular pressure avoids further deterioration of the visual field in most
      patients. Other studies have dealt with different strategies in open angle
      glaucoma. The Advanced Glaucoma Intervention Study (AGIS) has investigated
      different therapeutic sequences in advanced glaucoma while the Collaborative
      Initial Glaucoma Treatment Study (CIGTS) and the Early Manifest Glaucoma Trial
      (EMGT), still in progress, have evaluated the efficacy and safety of surgery
      versus medical treatment and treatment versus no treatment, respectively, in new
      and low-grade glaucoma. These long-term studies have led to a better approach to
      ocular hypertension, normal tension glaucoma, initial glaucoma, and advanced
      glaucoma. This review presents the characteristics of these clinical studies,
      points out the problems linked to giving a fair and practical interpretation, and
      attempts to draw useful guidelines for daily clinical practice.

PMID- 12223956
TI  - [Sturge-Weber-Krabbe syndrome].

PMID- 12223957
TI  - [Nevus mimicking a basal cell carcinoma of the eyelid].
AB  - A clinicopathologic case of a 41-year-old female patient exhibited a single
      cutaneous tumor at the inner part of the free margin of the inferior left eyelid.
      It was a pink, fleshy, and nodular well-circumscribed exophytic mass with thin
      vessels on its surface. Experienced already for 20 years, this lesion had been
      observed 6 years before and has not exhibited much change since then. However,
      its clinical appearance argued for a possible small basal cell carcinoma, which
      had grown over the inferior left lachrymal duct. After surgical removal,
      histopathology showed that the tumor was an amelanotic dermal nevus. No
      disturbance of lachrymal drainage was observed after surgery. This case shows
      that nodular amelanotic tumors of the eyelid, even when located on the inner
      segment of the eyelid, may be a nevus.

PMID- 12223959
TI  - [Implication of VEGF, steroid hormones and neuropeptides in hair follicle cell
      responses].
AB  - Human hair follicles progress independently through the anagen, catagen, telogen
      and latency phases that correspond to growth arrest and hair shedding before
      initiation of a new anagen phase. Hair follicles are self-renewing and contain
      reservoirs of multi-potent stem cells. Identification of the messenger molecules
      and pathways operating in the growth and cycling of hair follicles, have provided
      substantial data. However, only a limited number of these signals is well
      understood. The specific response of hair follicle cells to these signals is
      correlated with the expression of their corresponding receptors. What regulates
      these responses? In this review, we will focus on the hair cycle and its control
      mechanisms. We will provide some elements in answer to these questions and
      present some of the markers of hair follicle cells, and hormonal and vascular
      growth factors, which may regulate respectively hair follicle cell metabolism and
      cycle, and the neuropeptide impact on hair follicle response and hair growth. The
      results of our study show the modifications in various expression patterns of
      receptors in dermal papilla cells, and demonstrate the cross-interaction between
      these different components. In conclusion, we present an accumulation of evidence
      suggesting that the regulation of hair growth requires a combination of hormonal,
      vascular and neuropeptide approaches that will provide further insight in
      defining new treatments for hair loss.

PMID- 12223960
TI  - [Hormonal interaction and hair growth].
AB  - Androgenetic alopecia (AGA) is the most common form of hair loss in men and
      women. This continuous process results in a form of alopecia that follows a
      definite pattern in those individuals who are genetically predisposed. Although
      clinically different, the pathogenetic pathways leading to this type of hair loss
      are thought to be similar in both sexes. A genetic predisposition is a feature of
      AGA, but the predisposing genes are still unknown. Our understanding, however, of
      the hormonal effects on hair growth is far more advanced. AGA can be defined as a
      dihydrotestosterone (DHT)-dependent process with continuous miniaturization of
      sensitive hair follicles. So far, we do not understand the molecular steps
      involved in androgen-dependent beard growth versus androgen-dependent hair loss.
      However, the local androgen metabolism plays a central role in the
      intrafollicular conversion of weak androgens, such as DHEAS, to more potent
      androgens such as T or DHT within the hair follicle. The dermal papilla plays a
      central role by exhibiting an array of important steroidogenic isoenzymes.
      Provided that the dermal papilla (DP) cell triggers and regulates the growth of
      hair follicles, this physiological role may be reflected by metabolic
      differences, which could account for differences in androgen sensitivity as
      observed in hair follicles from different body sites, and in conditions such as
      male pattern baldness. The observation of STS, 17beta-HSD, 3beta-HSD, 3alpha-HSD
      and type 2 5alpha-R-activity within the DP could be a clue to understanding the
      regulation of androgen action in the human hair follicle by local androgen
      modification on target cell level. Hence, some of the intrafollicular
      steroidogenic enzymes would be potential pharmaceutical targets for the treatment
      of AGA or hirsutism.

PMID- 12223961
TI  - [Genetic dissection of retinoic acid function in epidermis physiology].
AB  - The active metabolite of vitamin A (retinoic acid, RA) acts through the nuclear
      receptors RARalpha, beta and gamma and RXRalpha, beta and gamma. These receptors
      form RAR/RXR heterodimers, which bind to genetic regulatory DNA sequences and
      activate transcription of RA target genes. As RXR form heterodimers with a number
      of other nuclear receptors, such as the vitamin D3 receptor (VDR) and are
      involved in several signaling pathways. In the skin, RARgamma and RXRalpha
      predominate, but RARalpha and RXRbeta are also expressed. To elucidate the role
      of RA in skin physiology, we produced mutant mouse lines null for RAR or RXR. On
      the one hand, null mutations for RARa or RXRbeta have no effect on the skin,
      whereas a RARgamma-null mutation induces alterations in the granular cell layer.
      On the other, genetic inactivation of RXRa leads to embryonic lethality before
      epidermal development. Consequently, to determine the role of RXRa in adult mice,
      studies were performed using conditional somatic mutagenesis (permitting
      inactivation of a given gene in a specific tissue and in a time-dependent
      manner). Using this novel genetic approach, mutant mice were obtained in which
      RXRalpha was not expressed in the skin. These mice developed hair follicle
      degeneration, then alopecia, similar to that observed in VDR-null mutants,
      suggesting that hair follicle homeostasis depends on RXRalpha/VDR heterodimers. A
      similar genetic approach applied to the RARgamma locus demonstrated that topical
      administration of RA on the skin activates RARgamma/RXR heterodimers in
      suprabasal cells, and induces expression of a paracrine growth factor (HB-EGF) in
      these cells which, in turn, stimulates the proliferation of basal cells.

PMID- 12223962
TI  - [Androgenetic alopecia].
AB  - Androgenetic alopecia (AGA) is the combined result of an androgen-dependent
      process and genetic transmission. These characteristics have mainly, if not
      exclusively, been demonstrated in men and perhaps improperly extended to women.
      When considering the androgen-dependent process, AGA must only be limited to the
      androgen receptor areas. In the scalp, these receptors have only been detected in
      the frontal and vertex areas but never in the temporal or the occipital areas.
      Male AGA exhibits these clinical features, whereas in women hair loss is rarely
      limited to this localization, even when large areas of hair loss often appear
      with age. It is now commonly accepted that male AGA is associated with an
      increase in 5 alpha reductase activity leading to an increase in local production
      of dihydrotestosterone. The mechanism by which the local dihydrotestosterone
      increase leads to hair follicle loss is not clearly demonstrated. Inhibition of
      cell proliferation in the dermal papilla and a vascular process based on the
      inhibition in local production of vascular endothelial growth factor (VEGF) have
      been proposed. The increase in 5 alpha reductase activity is genetic and depends
      on androgen receptor polymorphism, characterized by a decrease in the number of
      CAG sequences on the exon 1. Male AGA is associated with an insulin-resistant
      process and to a higher risk of polycystic ovary in the lineage. Therapeutically,
      this hormone-dependent process explains the well demonstrated efficacy of 5 alpha
      reductase inhibitors. In women, except in some rare cases, alopecia is diffuse
      and the mechanisms are different. Their origin is unknown, and probably
      ambiguous. Based on an association with Hashimoto's thyroiditis, an auto-immune
      origin could be suggested in some cases. Alopecia is unaffected by thyroid
      substitution. Pharmacological doses of oestrogens (pregnancy, contraception) have
      a beneficial effect on such alopecia, probably through different mechanisms: anti
      androgen effect, increased VEGF, proliferative effect of dermal papilla cells.
      However, it is important to mention that the dermal papilla has an aromatase,
      particularly in the occipital area, the activity of which has not been assessed
      in female alopecia. In practice 5 alpha reductase inhibitors are ineffective in
      women. It is likely that the predominance observed in the frontal and vertex
      areas, occasionally in elderly women, is a result of the two combined disorders,
      the almost physiological androgen-dependent hair loss combined with diffuse loss.
      Pharmacological doses of oestrogens associated with anti-androgen progesterone
      like agents are widely used with positive results, but not demonstrated by
      clinical trials.

PMID- 12223963
TI  - [Hirsutism and hypertrichosis in adults: investigations and treatment].
AB  - Hypertrichosis, characterized by increased hair growth located in non-androgen
      dependent areas, does not justify the monitoring of hormone levels, conversely to
      hirsutism, with increased hair growth in androgen-dependent areas of the female
      genitals. Adult hypertrichosis is iatrogenic (minoxidil, ciclosporine, diazoxide
      or glucocorticosteroids), of metabolic origin (porphyria), nutritional (anorexia)
      or paraneoplastic (hypertrichosis lanuoginosa). Metabolic or general assessment
      can help clinical diagnosis. In non-iatrogenic hirsutism the following must be
      eliminated: 1) a virilizing tumor (ovarian, adrenal) when confronted with rapid
      progression or recent hirsutism, plasma testosterone (T)>1.5ng/ml and/or (adrenal
      tumor) DHEA-sulfate (DHEAS)>700 microgram/dl and associated with hypertension; 2)
      when confronted with characteristic signs of hirsutism, Cushing's syndrome (post
      dexamethasone cortisol), hyperprolactinemia (pooled PRL), or acromegalia (IGF1).
      Measurement of 17-OH-progesterone at 8 am on the 4th day of the cycle detects the
      late manifestation homozygous forms of a 21-hydroxylase (21OHD) block. The more
      frequent forms are: 1) ovarian polymicrocystic or hirsutism-anovulation syndromes
      without other causes (LH/FSH, T, hyperinsulinemia, sonography); 2) functional
      adrenal hyperandrogenia (increased DHEAS without organic cause); 3) idiopathic
      hirsutism. Treatment can be local (discoloration, depilation, diathermo
      coagulation, laser). Treatment of hirsutism of organic origin is etiologic. The
      inhibitory effects of glucocorticosteroids are mediated by 21OHD. The most
      effective treatments are anti-androgenic: cyproterone acetate, progesterone-like
      and anti-gonadotropic (contraceptive) agents; and the only product in France
      officially indicated in hirsutism , spironolactone (anti-mineralocorticosteroid);
      and flutamide, pure anti-androgen (probably hepatoxic). Finasteride (type II 5
      alpha-reductase inhibitor) appears less effective. Estrogen-progestagen-like
      agents can be associated with anti-androgens. We should also mention the GnRH
      agonists, and finally, dietetics and metformine (in cases of insulin-resistance).

PMID- 12223964
TI  - [Pilar dysplasias].
AB  - Pilar dysplasias are congenital or acquired disorders, they are characterized by
      hair abnormalities in color, density, length and structure. Optic microscopy and
      polarized light microscopy analysis of piliary shafts provides important
      informations and contribute to the diagnosis of complex syndromes. Many
      pathological profiles can be visualized, some are specific, other are not. Some
      authors use a particularly convenient classification including 3 groups: in the
      first, piliary shaft abnormalities are isolated, in the second the abnormalities
      correspond to complex syndromes, and in the third they are associated with
      various malformations. Based on some clinical cases, we will describe various
      types of pilar dysplasias and we present recent advances, particularly in
      genetics.

PMID- 12223965
TI  - [Etiologic diagnosis and behaviour when confronted with abnormal hair growth in a
      child].
AB  - Knowledge of the physiology of hair follicle growth and its relationship to the
      endocrine and the metabolic system is essential in understanding abnormalities in
      hair development or hirsutism. Although there is no sexual dysmorphism in the
      distribution of hair follicles, there are many factors that induce hair growth.
      The first clinical measure is to differentiate all the intrinsic causes from
      auxologic and normal psychomotor development related to ethnic, racial and
      hereditary differences (generalized congenital or idiopathic hypertrichosis) and
      congenital causes within the context of a multi-malformation syndrome in which
      hirsutism is associated with mental retardation (Cornelia de Lange's syndrome),
      major hypotrophy (leprechaunism) or with abnormalities of the limbs (Rubinstein
      Taybi's syndrome or mucopolysaccharidosis). In these cases, the hormone balance
      is normal and genetic and/or metabolic explorations are required. Secondly,
      virilism may occur with hirsutism combining pubis and axillary hair growth,
      hypertrophy of the clitoris, and android characteristics. This results from
      hyperandrogenia with increased circulation of plasma androgens. Dynamic hormone
      tests (ACTH test and dectanyl suppression test), together with sonography help to
      determine the adrenal (hyperplasia, more frequent than tumors), gonadic (tumors,
      cysts or gonadic dysgenesis) or paraneoplastic origins (choriocarcinoma). In
      practice, most hirsutism is considered as idiopathic.

PMID- 12223966
TI  - [Interactive clinical cases].

PMID- 12223967
TI  - [Alopecia areata: update on therapy].
AB  - The management of patients with alopecia areata is obviously not restricted to
      the prescription of a treatment inducing hair growth. It requires thorough
      exploration (history of hair loss, treatments and concomitant pathologies),
      detailed clinical examination of the integument and palpation of the thyroid. The
      patient must, systematically, be given a simple explanation of his/her pathology,
      thus avoiding any feelings of mystery, hopelessness and guilt and hence
      paradoxically turning alopecia into "just another disease", even if flares are
      unpredictable and cannot always be treated. Innovations over the past few years
      have not met dermatologist's expectations: in particular immunosuppressors
      administered locally have not shown efficacy in human, as opposed to animal
      models of alopecia areata. Moreover, we must remain critical and rigorous with
      regard to "false" innovations: several recent publications are, methodologically,
      open to criticism. Older products provide clear descriptions of their indications
      and use, and relatively standardize the therapeutic approach to alopecia. Some of
      them lead to hair growth on the treated area: localized immuno-therapy that in
      certain cases induces hair growth where other treatments have failed. PUVA
      therapy, however, because of frequent relapses on withdrawal and the
      characteristic recurrence of alopecia, rapidly leads to the use of high
      cumulative doses; balneo-PUVA therapy is effective with lower doses (PUVA
      turban). Recently, UVB TL01 has shown efficacy in anecdotal studies. Local
      corticosteroids; notably injectable and anthralin, an old treatment which remains
      a useful therapeutic approach in alopecia areata plaques and in the ophiasic
      forms in children and adults. Finally, among the available treatment arms,
      systemic corticosteroids still have a place in recent extended forms: although
      still under experimentation, the bolus appears efficient during the primary
      episodes of alopecia areata, when administered within the first three months

PMID- 12223968
TI  - [Indications for micrograft hair transplantation].
AB  - Advances in treatment of androgenetic alopecia have led to the development of
      novel medical or surgical therapies adapted to the severity of hair loss and
      balding. Follicular units or tiny micro-graft hair transplants are a fundamental
      technical progress. This technique leads to the simple and painless permanent
      restoration of hair in male and female baldness. It provides the patient with a
      group of 1 to 3 hairs, emerging from a single orifice. The difference between
      androgenic receptors of occipital areas and those of other areas explains the
      permanent nature of the implanted hair growth. The degree of male or female
      androgenetic alopecia can be determined according to Hamilton's static
      classification or Ludwig's Classification, or it can be measured and monitored
      more accurately with Bouhanna's Dynamic Multifactorial Classification. The
      current indications for micro-graft transplantation are

PMID- 12223969
TI  - [The hair follicle as a target for gene therapy].
AB  - The hair follicle possesses progenitor cells required for continuous hair
      follicle cycling and for epidermal keratinocytes, melanocytes and Langerhans
      cells. These different cell types can be the target of topical gene delivery in
      the skin of the mouse. Using a combination of liposomes and DNA, we demonstrate
      the feasibility of targeting hair follicle cells in human scalp xenografts. We
      consider liposome composition and stage of the hair cycle as important parameters
      influencing transfection of human hair follicles. Transfection is possible only
      during the early anagen phase. Factors and obstacles for the use of gene therapy
      in treating alopecia and skin diseases are discussed. A theoretical framework for
      future treatment of cutaneous and systemic disorders using gene therapy is
      presented.

PMID- 12223971
TI  - [Imaging of chilhood and adolescent scoliosis].
AB  - Scoliosis is frequent, especially during the peripubertal period, which
      corresponds to the period of greatest activity. About 75% of scoliosis are
      idiopathic, while the remaining 25% can be divided into neuromuscular, congenital
      and miscellaneous etiologies. When it is associated with pain, a comprehensive
      work up should be undertaken to identify the underlying etiology of the
      scoliosis. Idiopathic scoliosis is typically evaluated using standard
      radiographs. The number of follow-up radiographs and radiation exposure must be
      maintained to a minimum. Radiation safety guidelines and protocols must be
      implemented. Large cassettes can be replaced by digital acquisitions using units
      with reconstruction software. The technique of evaluation of these scoliosis
      series radiographs as well as their results will be reviewed. Recent data
      regarding the evaluation of spinal and pelvic balance parameters in the standing
      position will be introduced. Atypical idiopathic and other scoliosis require
      additional evaluation. Computed tomography, with 2D and 3D reformations, is ideal
      for evaluation of bony anomalies. MRI is ideal for evaluation of the spinal canal
      and cord, from the skull base down to the sacrum, for all patients with surgical
      scoliosis or patients with neurological symptoms. The increased availability of
      MR imaging has resulted in an increased number of so-called idiopathic
      asymptomatic scoliosis where an underlying anomaly can be identified.

PMID- 12223972
TI  - [Evaluation of spinal alignment disorders in adults].
AB  - Evaluation of the alignment of the spine in the frontal and sagittal planes is an
      important part in the work up of many disorders of the spine. This type of study
      requires only frontal and lateral 30 x 90cm radiographs performed in the standing
      position and including spine, pelvis and proximal femurs. The relationship
      between spine, pelvis and lower limbs is stressed.

PMID- 12223973
TI  - [Imaging of the lumbar spine].
AB  - The role of conventional radiographs in the evaluation of the lumbar spine
      remains unchanged. The respective place of CT and MRI in the evaluation of lumbar
      spine disorders has not significantly changed in spite of technical advances.
      However, their diagnostic capabilities have improved.

PMID- 12223974
TI  - [Imaging of lumbar stenosis].
AB  - The spinal canal is a type of articulated pipe, with rigid rings articulated by
      joints. It can be divided into a central part, which contains the dural sac, and
      lateral parts, which contain the nerve roots. The role of imaging is to detect
      the presence and characterize the nature, level, and severity of stenotic lesions
      and their impact on neural elements. Stenoses can be constitutional or acquired
      and involve the central and/or lateral canal. Constitutional stenoses affect both
      rigid and soft segments whereas acquired stenoses affect mainly the mobile
      segments. Signs of constitutional stenoses at conventional radiography, CT and
      MRI will be described. Acquired stenoses are multi-factorial in etiology and more
      difficult to evaluate. Intra-spinal soft tissues and dynamic factors, poorly
      assessed at CT and MRI (static imaging), play a major role in this type of
      stenoses. Currently, only myelography with dynamic evaluation is able to
      demonstrate the importance of these factors or degree of dynamic stenosis. The
      lateral canal is divided in three parts: two mobile segments (disco-articular
      interval, and intervertebral foramen) on each side of a fixed bony segment
      (lateral recess). The different types of stenoses involving these segments and
      best imaging technique to demonstrate their presence are described.

PMID- 12223975
TI  - [Thoraco-lumbar disc disease with nerve root impingement and differential
      diagnosis].
AB  - This paper will review the diagnostic imaging work-up of disc-related nerve root
      impingement including the role and technique of CT and MRI. Clinical and
      anatomical elements will be reviewed along with considerations regarding the
      radiology report, including a review of the proper descriptive terminology.
      Finally, clinical and imaging pitfalls will be discussed. In addition to specific
      features related to thoracic and lumbar segments, clinical and imaging
      differential diagnoses are reviewed: non-disc related radicular pain (intradural
      or extra-spinal), differential diagnosis of "enlarged" nerve roots (free disc
      fragment, cyst of a nerve root sleeve, tumors, normal variants.).

PMID- 12223976
TI  - Calcipotriol and betamethasone dipropionate (Dovobet, Daivobet): a new
      formulation for the treatment of psoriasis.
AB  - A new compound product containing calcipotriol 50 nanograms per gm and
      betamethasone dipropionate 0.5mg per gm (Dovobet, LEO Pharma) in an ointment base
      was recently introduced in Canada for the treatment of psoriasis. Known as
      Daivobet in Europe, it was introduced to the Danish Market in 2001, and approved
      for marketing by the European Union. This compound has been shown to be more
      active than either agent used along. The efficacy of once daily application was
      not shown to be different from that of twice daily use.

PMID- 12223977
TI  - The utility of patch testing children with atopic dermatitis.
AB  - Allergic contact dermatitis (ACD) is more frequent in the pediatric population
      and in children with atopic dermatitis (AD) than has hitherto been appreciated.
      Patch testing, which is mediated by different immune mechanisms than prick skin
      testing, is both safe and diagnostically useful for individuals with AD. It may
      help to identify exacerbating allergies, e.g., constituents of topical treatments
      in refractory AD and to formulate treatment plans that feature preventive
      avoidance of the offending allergens.

PMID- 12223978
TI  - Clindoxyl gel for the treatment of acne vulgaris.
AB  - Clindoxyl Gel (Stiefel) is a combination of 1% clindamycin phosphate and 5%
      benzoyl peroxide in a gel vehicle that is well tolerated and more efficacious
      than either active agent alone or the vehicle in reducing lesion counts and
      improving global scores in patients with moderate acne. It was approved for once
      daily use in Canada in November 2001.

PMID- 12223979
TI  - Systemic antibiotic therapy for acne: a review.
AB  - Acne is a multifactorial disease of the pilosebaceous unit in the skin. Four
      contributing pathogenic factors need to be elucidated and include excess sebum
      production, follicular hyperkeratinization, colonization of the pilosebaceous
      unit by Propionibacterium acnes, which is a gram positive anaerobic diphtheroid,
      and the release of inflammatory mediators into the follicle and dermis. One or
      more of these factors are targeted by each of the systemic therapies for this
      disease and its variant, including systemic antibiotic therapies, which will be
      reviewed here.

PMID- 12223980
TI  - Seronegative oligoarthritis: a 23-year follow-up study.
AB  - The aim of the study was to investigate the long-term outcome of non-specific
      seronegative oligoarthritis in adults. The study included 64 adult patients with
      recent (<6 months) seronegative oligoarthritis (rheumatoid factor negative,
      number of swollen joints 1-4 during the first 6 months). Follow-up examinations
      were carried out at onset and at 1, 3 and 8 years from entry. A total of 47
      patients attended the 23-year follow-up. The endpoint outcome was good. Seven had
      mild erosions in the hands or feet. Only one patient with HLA-B27 developed
      bilateral sacroiliitis. Three patients had retired from work because of joint
      disease. The functional outcome of the patients analysed by HAQ was very good
      after 23 years: 0 in 33 and 0.1-0.9 in 12 of the 47 patients. Reclassification
      revealed a certain heterogeneity: one case each of rheumatoid arthritis, SLE and
      ankylosing spondylitis, two cases of post-traumatic arthritis, four of
      osteoarthrosis, and six of possible reactive arthritis. Out of the remaining 49
      patients 15 were HLA-B27 positive and 16 had at least one of the psoriasis
      related HLA antigens (HLA-B13, 17, w16). In conclusion, our 23-year prospective
      follow-up study of patients with seronegative oligoarthritis confirms their
      favourable outcome. The reason is that the endpoint diagnoses seemed to be
      similar to those of mild spondylarthropathies.

PMID- 12223981
TI  - Disease manifestations and HLA antigens in psoriatic arthritis in northern
      Sweden.
AB  - The aim of this study was to identify potential markers of aggressive joint
      manifestations and HLA associations in patients with psoriatic arthritis (PsA) in
      northern Sweden. Patients with PsA were examined clinically, with laboratory
      tests and radiologically. The classification of the disease was based on
      peripheral and/or axial engagement. HLA B17, B37 and B62 were significantly
      increased in PsA patients. Univariate analyses suggest that the HLA antigens B37,
      B62 and some clinical variables were associated with disease course. However, in
      multivariate analyses distal interphalangeal joint affliction and polyarticular
      manifestations were the only variables remaining significantly associated with
      irreversible joint destruction or deformity. There were no significant effects of
      HLA antigens. In this cross-sectional study, clinical manifestations were more
      reliable predictors of aggressive joint damage than were specific HLA antigens.
      However, HLA antigens seemed to modify the expression of the joint disease rather
      than being involved in joint disease susceptibility.

PMID- 12223982
TI  - Attained adult height in juvenile rheumatoid arthritis with or without
      corticosteroid treatment.
AB  - Growth impairment has been described in patients with juvenile rheumatoid
      arthritis (JRA). Both the direct action of underlying disease and prolonged
      corticosteroid usage for disease management may contribute to growth impairment.
      The purpose of this retrospective study was to evaluate the effect of systemic
      corticosteroid treatment on attained adult height in patients with JRA. We
      reviewed patients who first visited our hospital from 1973 to 1995 with a
      diagnosis of JRA. Adult height (AH) and the reported parental heights of these
      patients were recorded. Target height (TH) is estimated according to midparental
      height. Patients who never had or had only transient (less than 1 week) systemic
      corticosteroid therapy were classified as group 1. Group 2 included patients who
      had corticosteroid therapy for more than 1 week but never continuously for more
      than 12 months, and group 3 included patients on long-term steroid treatment
      (continuously for more than 1 year). Height data were analysed using adult height
      and the difference between adult height and target height (AH minus TH). Thirty
      three patients fulfilling the diagnostic criteria for JRA were reviewed. Fourteen
      belonged to group 1, 13 to group 2 and six to group 3. The difference between
      adult height and target height in group 1 was 2.96 +/- 4.54 cm, in group 2 0.71
      +/- 6.08 cm (group 1 vs. group 2, P = 0.28), and in group 3 -11.65 +/- 10.71 cm
      (group 1 vs. group 3, P<0.05). In 15 patients who never received corticosteroid
      therapy continuously for more than 1 year, AH-TH was statistically correlated
      neither with the cumulative corticosteroid exposure dose nor with cumulative
      corticosteroid exposure period by linear regression ( P = 0.408, P = 0.278,
      respectively). We concluded that continuous systemic corticosteroid usage for
      less than 1 year does not affect attained adult height in JRA patients; however,
      prolonged corticosteroid treatment for more than 1 year can lead to irreversible
      growth impairment.

PMID- 12223983
TI  - Influenza virus vaccination of patients with SLE: effects on generation of
      autoantibodies.
AB  - The sera of 24 women with SLE who received influenza vaccine were tested by ELISA
      for anti-DNA, anticardiolipin, anti-Sm, anti-Sm/RNP, anti-Ro and anti-La. Blood
      samples were withdrawn at the time of vaccination and 6 and 12 weeks after
      vaccination. The mean age at enrolment into the study was 46.1 years. The mean
      disease duration was 9.1 years. SLEDAI scores were 6.6 at vaccination, 4.9 at 6
      weeks and 5.1 at week 12. The vaccine was not associated with the generation of
      anti-DNA. At time of vaccination a single patient had anti-Sm, four patients had
      anti-Sm/RNP antibodies, none of the patients had anti-La antibody and six had
      anti-Ro antibodies. Six weeks after vaccination four, eight, nine and three
      patients had autoantibodies reacting with Sm, Sm/RNP, Ro and La, respectively.
      Twelve weeks after vaccination none of the patients had anti-Sm, three had anti
      Sm/RNP, five had anti-Ro and two had anti-La antibodies. Following vaccination
      six and three patients developed IgG and IgM anticardiolipin antibodies,
      respectively. In summary, although the influenza virus vaccine is clinically safe
      for patients with SLE it may trigger the generation of autoantibodies. This
      effect is usually short term and has no clinical significance.

PMID- 12223984
TI  - Microscopic haematuria in giant cell arteritis.
AB  - Giant cell arteritis (GCA) is traditionally considered to spare the kidney,
      although an uncontrolled study reported microscopic haematuria in 10 out of 30
      patients with GCA. To study the frequency and the characteristics of microscopic
      haematuria in GCA, we retrospectively studied 42 patients with biopsy-proven GCA,
      39 patients with polymyalgia rheumatica (PMR) and 62 control patients >or=60
      years of age, admitted to the general internal medicine unit. Patients with
      pyuria, significant bacteriuria or a known haematuric disorder were excluded.
      Microscopic haematuria was defined as the presence of >5 red blood cells (RBC)
      per high-power field (sediment counts) or of >8 RBC/microl (direct counting).
      Microscopic haematuria was present at presentation in 47.6% of the GCA patients,
      versus 17.9% of the PMR patients (P = 0.005) and 21.0% of the control patients (P
      = 0.008). Urinary RBC were predominantly dysmorphic in all GCA patients in whom
      RBC morphology was assessed (n = 7). Presenting symptoms, renal function,
      arterial blood pressure and degree of leukocyturia did not differ significantly
      between GCA patients with or without haematuria. After the initiation of
      corticosteroid therapy, microscopic haematuria was no longer detectable in 25 of
      35 GCA patients (71.4%). Microscopic haematuria of renal origin is frequent but
      generally benign in patients with GCA. Its presence, if unassociated with blood
      pressure elevation or renal function deterioration, helps to rule in rather than
      to rule out the diagnosis of GCA. In the typical setting invasive urologic and
      nephrologic work-up may not be warranted.

PMID- 12223985
TI  - Antistreptococcal response is exaggerated in children with familial Mediterranean
      fever.
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive disorder. Although
      the pathogenesis of the disease is not yet completely understood, enhanced acute
      phase responsiveness is considered to be one of the most important mechanisms.
      The presence of high levels of antistreptolysin O (ASO) antibodies and
      streptococcus-associated diseases, such as acute poststreptococcal
      glomerulonephritis (AGN) and acute rheumatic fever (ARF), has been reported in
      patients with FMF. In order to better understand the effect of FMF on
      antistreptococcal antibody response, we measured ASO and antideoxyribonuclease B
      (anti-DNAse B) levels in patients with FMF and compared them with those in
      healthy controls. The study consisted of two parts. In the first step,
      antistreptococcal antibody levels were analysed in 44 patients with FMF and 165
      healthy children who had no history or clinical evidence of upper respiratory
      tract infection (URTI) for the last 4 months. In the second step,
      antistreptococcal antibody levels were measured in 15 patients with FMF and 22
      healthy controls in response to documented group A beta-haemolytic streptococcal
      pharyngitis. In the first part of the study, ASO and anti-DNAse B levels in
      patients with FMF were found to be significantly higher than those in healthy
      controls (P<0.001). In the second part, ASO and anti-DNAse B titres were found to
      be significantly higher in patients with FMF than in controls (P<0.001 and <0.05,
      respectively) 4 weeks after a positive throat culture. We concluded that patients
      with FMF have an exaggerated response to streptococcal antigens and might be
      prone to poststreptococcal non-suppurative complications, such as ARF.

PMID- 12223986
TI  - IgG anti-beta(2) glycoprotein I antibodies in Malaysian patients with
      antiphospholipid syndrome and systemic lupus erythematosus: prevalence and
      clinical correlations.
AB  - The aim of this study was to investigate the incidence of IgG anticardiolipin
      antibody (ACL) and IgG anti-beta(2) glycoprotein I antibody (anti-beta2GPI)
      positivity in patients with primary or secondary antiphospholipid syndrome (APS)
      and systemic lupus erythematosus (SLE), to assess the association between IgG ACL
      and anti-beta2GPI, and the relationship between the presence of ACL and anti
      beta2GPI with the clinical manifestations of APS. IgG ACL and IgG anti-beta2GPI
      levels were measured in 51 SLE patients, 20 patients with SLE and APS (secondary
      APS) and 11 primary APS patients using commercially available ELISA kits.
      Relationships between laboratory data and clinical manifestations of the patients
      were examined. The incidence of IgG ACL positivity was significantly higher in
      primary (36.4%) and secondary (40%) APS than in SLE (13.7%) patients (P = 0.02).
      The incidence of IgG anti-beta2GPI positivity was significantly higher in primary
      (54.5%) and secondary (35%) APS than in SLE (7.8%) patients (P = 0.0006). Mean
      levels of IgG ACL and anti-beta2GPI were significantly higher in the primary and
      secondary APS than in the SLE patients (P = 0.002 for both). A significant
      relationship was found between IgG ACL and IgG anti-beta2GPI (P = 0.01, R(2) =
      0.56). There was a significant correlation between the presence of IgG ACL and a
      history of thrombosis in the combined primary and secondary APS group, but not in
      SLE patients. In conclusion, in this study IgG ACL and IgG anti-beta2GPI are
      closely related and mean levels of IgG ACL and IgG anti-beta2GPI are higher in
      patients with either primary or secondary APS than in SLE patients.

PMID- 12223987
TI  - Antiphospholipid antibodies in a heterogeneous group of patients: experience from
      a central laboratory.
AB  - The aim of this study was to evaluate the prevalence and the performance of lupus
      anticoagulant (LA) tests in a heterogeneous group of patients and to investigate
      the sociodemographic characteristics, patterns of referral, clinical
      manifestations and outcomes among these patients. The medical charts of 725
      patients referred to a central coagulation laboratory during a 12-month period
      for LA were reviewed. The data collected included demographic characteristics,
      the specialty of the referring physicians, the clinical indications for ordering
      the test, and the influence of the test results on the diagnosis and the
      treatment approach. Special attention was paid to identifying clinical
      manifestations known to be associated with antiphospholipid antibodies (APLA). A
      positive test was defined by abnormal results obtained by at least two techniques
      from the reagents used and confirmed by a platelet-neutralising procedure. Chi(2)
      and t-tests were used for independent samples. Fifty-six patients (7.7%) were
      found to have LA. Rheumatologists and gynaecologists emerged as the major
      contributors to this group. The presence of LA was significantly associated only
      with systemic lupus erythematosus and thrombocytopenia. The number of patients
      treated with antiaggregants or anticoagulants tripled following the test results.
      A positive dRVVT test strongly correlated with elevated anticardiolipin
      antibodies. We concluded that LA tests are ordered by a variety of physicians but
      yield better results when ordered by rheumatologists and gynaecologists. In this
      heterogeneous cohort, it was most useful in the investigation of thrombocytopenia
      and suggests a pathogenetic role in this condition. The dRVVT test correlates
      most closely with elevated anticardiolipin antibodies.

PMID- 12223988
TI  - Idiopathic inflammatory myopathy with diffuse alveolar damage.
AB  - Interstitial lung disease (ILD) in patients with myositis is defined by the
      presence of interstitial changes on radiographic examination. The reported
      prevalence of ILD varies from 0% to nearly 50%. However, only rarely has the
      pathological pattern of diffuse alveolar damage (DAD) associated with idiopathic
      inflammatory myopathy (IIM) been reported. We report five patients with IIM (one
      with dermatomyositis, one with polymyositis, and three with amyopathic
      dermatomyositis) and respiratory failure. Four underwent open lung biopsy with
      pathological proof of diffuse alveolar damage (DAD). Despite intensive
      immunosuppressive therapy, all of them died. In addition to the case reports, we
      discuss DAD in patients with IIM.

PMID- 12223989
TI  - Tuberculosis of the greater trochanteric bursa occurring 51 years after
      tuberculous nephritis.
AB  - We present a case of tuberculous greater trochanteric bursitis occurring 51 years
      after tuberculous nephritis in a 71-year-old man. Radiographs of the affected hip
      revealed focal osteolysis of the greater trochanter and calcification in the
      surrounding soft tissues. Contrast-enhanced CT scans and MRI revealed that the
      enlarged bursa extended into the femoral intermuscular spaces. Bacterial culture
      of the biopsied bursa grew Mycobacterium tuberculosis. Total excision of the
      infected bursa, combined with antituberculous therapy, was curative. Tuberculosis
      of the greater trochanteric bursa should be included in the differential
      diagnosis of chronic hip pain. New tuberculous musculoskeletal lesions can occur
      elsewhere in the body many years after primary tuberculous lesions have healed.

PMID- 12223990
TI  - Brachial plexopathy associated with systemic sclerosis.
AB  - Neurological involvement is uncommon in systemic sclerosis. Most of the reported
      cases concern trigeminal neuropathy or peripheral nerve entrapment. We report a
      third case of brachial plexopathy, presumably related to vasculitis, in a patient
      with systemic sclerosis, which improved after cyclophosphamide therapy.

PMID- 12223991
TI  - Synovial chondromatosis of the elbow presenting as a soft tissue tumour.
AB  - Synovial chondromatosis of the elbow is not common. Bursitis, neurocompression
      and locking are the usual symptoms. We describe a case which was initially
      thought to be a soft tissue tumour, i.e. a synovial sarcoma.

PMID- 12223992
TI  - Coexistence of osteopoikilosis and discoid lupus erythematosus: a case report.
AB  - Osteopoikilosis is an uncommon, benign sclerosing bone dysplasia characterised by
      typical roentgenographic findings and usually seen in patients with
      dermatological problems. We report a case of osteopoikilosis and discoid lupus
      erythematosus presenting with skin and mucosal involvement, an association that
      has never previously been reported. We also discuss the differential diagnosis
      and the clinical pathologies accompanying osteopoikilosis in the literature.

PMID- 12223993
TI  - Adult Henoch-Schonlein purpura with glomerulonephritis and paroxysmal nocturnal
      haemoglobinuria: an uncommon association.
AB  - Henoch-Schonlein purpura (HSP) is considered to be a small blood vessel systemic
      vasculitis. Numerous microorganisms have been implicated in triggering HSP. We
      describe an unusual case of HSP with glomerulonephritis and renal failure
      requiring haemodialysis in a young adult man who subsequently developed
      paroxysmal nocturnal haemoglobinuria (PNH) with several haemolytic episodes.
      Bacterial infections, especially those of the respiratory and urinary tract,
      might trigger both the diseases.

PMID- 12223994
TI  - Mitochondrial disease mimicking polymyositis: a case report.
AB  - The authors report on a 34-year-old woman who had developed severe weakness and
      reduction in grip strength in both upper and lower limbs. Laboratory blood tests
      revealed increased levels of muscle enzyme. The presence of progressive bilateral
      ptosis and external ophthalmoplegia raised the suspicion of a mitochondrial
      disease, subsequently confirmed by deltoid biopsy and genetic analysis of
      mitochondrial DNA that showed a deletion indicative of Kearns-Sayre syndrome. In
      this report we emphasise the need for a differential diagnosis between myositis
      and other myopathies, particularly the mitochondrial ones.

PMID- 12223995
TI  - Arthritis associated with recurrent erythema multiforme responding to oral
      acyclovir.
AB  - Erythema multiforme is a skin condition frequently associated with herpes simplex
      virus and has a tendency to recur. Oral acyclovir has been successful in
      suppression of the disease. Here we report a patient who had recurrent erythema
      multiforme associated with recurrent polyarthritis that responded to oral
      acyclovir suppression therapy.

PMID- 12223996
TI  - Regional migratory osteoporosis: a pathogenetic hypothesis based on three cases
      and a review of the literature.
AB  - Regional migratory osteoporosis (RMO) is a migrating arthralgia of the weight
      bearing joints of the lower limb which mainly affects middle-aged males. Its
      aetiology is unknown. The association of RMO with generalised osteoporosis has
      recently been reported. A concurrent systemic osteoporosis was also reported in
      some cases of transient osteoporosis of the hip (TOH), a disorder closely related
      to RMO. In its turn, TOH is considered a reversible stage of avascular necrosis
      of the hip (AVN), and the aetiopathogenesis of both of them remains strongly
      debated. We report three cases of RMO associated with generalised severe
      idiopathic osteoporosis. Three men, in the fourth and fifth decades of life,
      complained of at least four episodes of arthralgia in the lower limbs, with a
      migratory pattern, radiographic focal osteoporosis and final clinical resolution.
      The most striking common feature of these patients was the presence of a severe
      systemic osteoporosis with a prevailing trabecular involvement. We suggest that a
      prolonged or exaggerated activation of regional acceleratory phenomena (RAP) is
      the cause of transient osteoporosis. Bone tissue microdamage due to osteoporosis
      may be the most frequent noxious stimulus that turns RAP on, and, bone tissue
      microfracture is the most prevalent consequence. When this pathogenetic pathway
      is activated, the progression from focal osteoporosis and bone marrow oedema to
      avascular necrosis is associated with the amount of structural damage.

PMID- 12223997
TI  - Primary central nervous system (CNS) lymphoma in immunocompetent patients.
AB  - Primary CNS lymphoma (PCNSL) has been increasing in incidence among both
      immunocompetent and immunocompromised patients. Today there is no uniform
      approach to the treatment of this disease. Whole brain irradiation (WBI) has been
      standard treatment, resulting in complete remission in the majority of patients,
      but with most patients relapsing and dying of their disease within 2 years after
      treatment. The addition of chemotherapy to WBI appears to prolong survival for
      patients younger than 60 years with median survival reaching a plateau at
      approximately 40 months. The issue of the best treatment for older patients
      remains controversial. Prospective studies will be needed, as it is impossible to
      draw conclusions from the nonrandomized small series published so far. This is
      because the prognostic variables of age and performance status to date have
      affected outcome more than therapy. In this review, some of the questions
      regarding the management of PCNSL are addressed. Since the role of radiotherapy
      remains unclear, we designed a new randomized multicenter study (G-PCNSL-SG-1
      trial) to investigate the optimal timing of WBI after high-dose methotrexate (HD
      MTX) chemotherapy.

PMID- 12223998
TI  - A randomized trial of chemotherapy with carmustine, etoposide, cytarabine, and
      melphalan (BEAM) plus peripheral stem cell transplantation (PBSCT) vs single
      agent high-dose chemotherapy followed by BEAM plus PBSCT in patients with
      relapsed Hodgkin's disease (HD-R2).

PMID- 12223999
TI  - Evaluation and clinical application of a new method for measuring activity of von
      Willebrand factor-cleaving metalloprotease (ADAMTS13).
AB  - Thrombotic thrombocytopenic purpura (TTP) is associated with acquired or
      congenital deficiency of a plasma von Willebrand factor-cleaving protease
      (VWFcp). Based on partial amino acid sequence and genome-wide linkage analysis of
      pedigrees with congenital TTP, VWFcp was recently identified as a new member of
      the ADAMTS family and designated ADAMTS13. We developed a new, rapid, and simple
      method for measuring VWFcp activity based on the positive correlation between VWF
      multimeric size and Ristocetin cofactor activity (VWF:RCo). After dilution of
      plasma with low ionic Tris buffer and activation of the protease with barium
      chloride, a VWF concentrate is digested in the presence of urea. Subsequently,
      the residual VWF:RCo of the samples is assessed and used to calculate the VWFcp
      activity of the samples. The accuracy of the new technique is verified by
      estimating VWFcp activity for 282 plasma samples with the RCo-based assay and the
      original immunoblotting assay. The method is reproducible as shown by low intra-
      and interassay coefficients of variation (2.8% and 7.5% for normal samples,
      respectively, and 8.7% and 12.9% for abnormal samples, respectively).
      Furthermore, the clinical application of the new method is illustrated by
      measuring VWFcp of 14 patients with 22 episodes of acute TTP as well as other
      thrombotic, thrombocytopenic, or hemolytic disorders. Severe VWFcp deficiency was
      restricted to patients with acute, classic TTP. The majority of patients with low
      titer inhibitor respond to plasma exchange treatment with increase of VWFcp
      activity, whereas VWFcp deficiency persists in some patients with high titer
      inhibitor despite clinical remission.

PMID- 12224000
TI  - Overview of 321 patients with idiopathic thrombocytopenic purpura. Retrospective
      analysis of the clinical features and response to therapy.
AB  - In this retrospective study, we evaluated the clinical features and the effects
      of various treatment modalities on the clinical course in patients diagnosed with
      idiopathic thrombocytopenic purpura (ITP) at our center between 1984-2000. We
      retrospectively examined the medical records of 321 (229 females, 92 males) ITP
      patients. One hundred and seventy-one (53.3%) patients were lost to follow-up.
      When evaluating the clinical features, all 321 patients were included; however,
      when the response to treatment modalities was evaluated only 150 patients
      followed up regularly were considered. The median age of the patients on initial
      diagnosis was 34 years (range: 14-78). At initial diagnosis, 235 (73.2%) patients
      had signs of bleeding. Of patients diagnosed with ITP initially, six later turned
      out to have systemic lupus erythematosus (SLE) and two myelodysplastic syndrome
      (MDS). The median follow-up of 150 patients followed up regularly was 30 months
      (range: 4-396). One hundred and thirty-seven of these subjects had an indication
      for treatment and 94.2% of them were administered either standard or high-dose
      steroids as the first-line therapy. Complete remission (CR) was defined as any
      platelet count >100,000/mm(3) lasting for 3 months or longer without treatment.
      CR was achieved in 51.9% of the patients given steroids as the initial therapy.
      During a median follow-up of 33 months, relapse occurred in 58.2% of these
      patients, and after a median follow-up of 11 months the rest of them were still
      in remission. Ninety-eight patients followed up regularly were administered
      second-line therapies. CR was obtained in 44.4% of the patients who used steroids
      as second-line therapy. Within a median follow-up of 15 months, 20.8% of these
      patients relapsed. Splenectomy was performed in 76 patients and CR was obtained
      in 68.4% of the regularly followed up patients. Relapse occurred within a median
      of 96 months in 15.4% of the patients who had CR. Kaplan-Meier curves showed that
      the duration of CR obtained by splenectomy was significantly higher than that
      obtained by steroids (p<0.001). The 10-year disease-free survivals in patients
      who used steroids and who underwent splenectomy were, respectively, 13% and 58%.
      In our adult ITP patients, steroids induced nearly similar rates of CR both as
      first-and second-line therapies. Splenectomy seems to be effective in patients
      unresponsive to steroids. The duration of CR obtained by splenectomy is
      significantly longer when compared with the duration of CR obtained by steroid
      therapy.

PMID- 12224001
TI  - Analysis of SH2D1A mutations in patients with severe Epstein-Barr virus
      infections, Burkitt's lymphoma, and Hodgkin's lymphoma.
AB  - Mutations or deletions in the SH2D1A (src homology 2 domain protein 1A) gene
      result in a severe immunodeficiency called X-linked lymphoproliferative (XLP)
      disease. XLP is primarily characterized by a defective immune response against
      the Epstein-Barr virus (EBV), resulting in an unusually severe and often fatal
      clinical course following EBV infection. The second major cause of death is the
      development of B cell lymphomas, both in EBV-infected and EBV-negative patients.
      To study whether the clinical manifestation of XLP gene defects and/or
      polymorphisms extends beyond the classically recognized phenotype, we analyzed
      patients for the presence of SH2D1A gene alterations who presented with fatal or
      nonfatal, yet unusually severe or chronic EBV infections, and other possibly EBV
      associated diseases, such as Hodgkin's lymphomas or nonendemic Burkitt's
      lymphomas and Burkitt-type leukemias. We identified mutations of the SH2D1A gene
      only in the majority of patients presenting with fatal mononucleosis or an XLP
      family history, but not in any of the other patients studied. The only alteration
      determined was a polymorphism in the 5' region of the SH2D1A gene both in patient
      groups as well as in controls.

PMID- 12224002
TI  - Feasibility of peripheral blood progenitor cell mobilization and harvest to
      support chemotherapy intensification in elderly patients with poor prognosis: non
      Hodgkin's lymphoma.
AB  - Mobilized peripheral blood progenitor cells (PBPC) are widely employed in the
      management of adult patients with high-risk non-Hodgkin's lymphoma (NHL), though
      their use in the elderly has received little attention. This study was mounted to
      assess the feasibility of the mobilization, harvesting, and reinfusion of PBPC in
      NHL patients aged >60. Twenty patients (median age: 67, range: 61-80) with poor
      prognosis NHL entered the pilot study: nine others were discarded for various
      reasons. Thus, the program was applicable to 69% of potential candidates.
      Fourteen patients were at onset and six were being treated for refractory disease
      or relapses. Mobilization was induced with cyclophosphamide 4 g/m(2), followed by
      5 micro g/kg per day granulocyte-colony stimulating factor (G-CSF) s.c. until
      PBPC collection or hemopoietic recovery. Sixteen patients (80%) displayed some
      signs of mobilization (CD34+: >5/ micro l). Maximum mobilization varied with
      median circulating CD34+ cells and colony forming units-granulocyte/macrophage
      (CFU-GM) peaks of 17.2/ micro l (range: 8.1-210) and 1,650/ml (range: 540
      62,900), respectively. A median of two leukaphereses resulted in the harvesting
      of a median of 6.7x10(6) (range: 0.3-33.6) CD34+/kg and 21.1x10(4) (range: 1.2
      209) CFU-GM/kg. Intensified therapy with intermediate-dose melphalan, associated
      or not with mitoxantrone, was delivered with autologous PBPC support to 13
      patients and always resulted in rapid and stable hemopoietic reconstitution. The
      program was well tolerated and no treatment-related deaths occurred. Twelve
      patients are still alive with a 5-year survival projection of 59%. In conclusion,
      the results demonstrate the feasibility of using autologous PBPC to support
      therapy intensification even in elderly patients.

PMID- 12224003
TI  - Platelet flow cytometric findings in patients undergoing conditioning therapy for
      allogeneic hematopoietic stem cell transplantation.
AB  - The conditioning regimen preceding hematopoietic stem cell transplantation (HSCT)
      causes a rapid decrease in the platelet count and signs of disseminated
      intravascular coagulation, possibly indicating platelet activation. As impacts
      during the conditioning regimen may predict later transplantation-associated
      complications, we investigated changes in platelet membrane glycoproteins (GP)
      and the liberation of microparticles. Platelet receptors and granules of 49
      patients undergoing HSCT were evaluated by flow cytometric analysis before and
      after the different phases of the conditioning regimen [chemotherapy, total body
      irradiation (TBI), therapy with antithymocyte globulin (ATG)] and final
      transplantation. Following chemotherapy a high surface expression of CD62P, a low
      mepacrine staining, and a reduced surface expression of CD42b (part of the GP
      Ib/V/IX complex) were found, indicating an irreversible activation of platelets.
      In addition, elevated levels of circulating microparticles were observed, which
      may reinforce the thrombosis risk in these patients. Treatment with ATG leads to
      an elevated surface expression of PAC-1 epitopes, which are neoepitopes appearing
      after activation of GP IIb/IIIa. However, a significant degranulation was not
      detectable, which may be the consequence of inhibitory influences on platelets
      during ATG-induced cytokine release syndrome. TBI and transplantation itself had
      no influence on platelets. This study was able to demonstrate activating effects
      on platelets by certain phases of the conditioning regimen in patients receiving
      HSCT. Chemotherapy, in particular, leads to a strong and irreversible platelet
      activation and a generation of microparticles, which may cause an increased
      thrombosis risk. Our findings underline the impact of platelets on the
      pathogenesis of hemostatic complications during HSCT.

PMID- 12224004
TI  - Liposomal daunorubicin (DaunoXome) for treatment of poor-risk acute leukemia.
AB  - Toxicity limits the use of anthracyclines in elderly sick patients and in heavily
      pretreated patients. Since the liposomal preparation of daunorubicin (DNR)
      (DaunoXome, or DNX) is expected to be less toxic than conventional DNR, we tested
      DNX combined with high-dose arabinosyl cytosine (HDAC) in 42 adult poor-risk
      acute leukemia patients. Thirty-one patients had acute non-lymphocytic leukemia
      (ANLL). Of these, 12 patients were newly diagnosed but were not eligible for
      standard induction treatment, 13 were in first relapse, and 6 were in second or
      subsequent relapse. Eleven patients had acute lymphocytic leukemia (ALL), in
      first (eight cases) or second (three cases) relapse. DNX was given i.v. in three
      doses of 80 or 100 mg/m(2) each (days 1-3) by a 60-min infusion in glucose 5%,
      followed by a 4-h infusion of HDAC 2 g/m(2) (days 1-5). Among 31 ANLL patients
      there were 16 (51%) complete remissions (CR), 5 deaths during induction, and 10
      failures. Among 11 ALL patients there were 10 CRs and 1 failure. The response
      rate was not affected by the overexpression of MDR-related proteins (PgP, MRP-1,
      and LRP). Non-hemopoietic toxicity was negligible, with no intestinal toxicity
      and only one case of gram-negative bacteremia. We conclude that DNX, in
      combination with HDAC, is an effective treatment for poor-risk adult AL. Because
      of the low non-hematologic toxicity, it can be used to reinduce remission in poor
      risk patients who are candidates for allogeneic bone marrow transplantation. The
      high CR rate observed in ALL requires confirmation.

PMID- 12224005
TI  - Gangrene of the toes in a patient with chronic myelogenous leukemia after long
      term hydroxyurea therapy.
AB  - Gangrene of the toes and digits appears to be a rare but very severe complication
      of long-term hydroxyurea therapy. Nothing is known regarding the pathophysiology
      and the type of vascular damage leading to this syndrome. Here we report a case
      of a 49-year-old male presenting with gangrene of the toes of both feet 4.5 years
      after initiation of hydroxyurea therapy for chronic myelogenous leukemia.
      Blisters on the toes occurred for the first time 9 months prior to
      hospitalization. Successively, all ten toes showed signs of beginning gangrene
      with one toe removed surgically 8 months before admission. Presence of diabetes
      mellitus or peripheral angiopathy was ruled out and platelet counts were within
      the physiologic range during the last years, excluding thrombocythemia as another
      rare cause for gangrene in patients with myeloproliferative diseases. Whereas
      perimalleolar ulcerations of the legs are a more common complication of
      hydroxyurea, gangrene of the toes as a consequence of hydroxyurea treatment has
      been described previously only once in the literature. At this point in time
      cessation of hydroxyurea treatment appears to be the only therapeutic option,
      thereby avoiding further progress of gangrene in patients with chronic
      myelogenous leukemia treated with hydroxyurea.

PMID- 12224006
TI  - Epstein-Barr virus-associated T-lymphoproliferative disease with hemophagocytic
      syndrome, followed by fatal intestinal B lymphoma in a young adult female with
      WHIM syndrome. Warts, hypogammaglobulinemia, infections, and myelokathexis.
AB  - A rare association of Epstein-Barr virus-associated T- and B-lymphoproliferative
      disease (EBV(+) T- and EBV(+) B-LPD) in a patient with WHIM (warts,
      hypogammaglobulinemia, infections, and myelokathexis) syndrome is reported. A 26
      year-old Japanese female, who had been treated for WHIM syndrome since early
      childhood, developed hemophagocytic syndrome associated with EBV(+) T-LPD at the
      lymph nodes and spleen. The disease rapidly resolved in response to prednisolone
      therapy. However, 6 weeks later, fatal EBV(+) B lymphoma unresponsive to
      chemotherapy occurred in the intestine and other organs. Caution must be
      exercised that the patient with WHIM syndrome may be at risk for EBV-LPD.

PMID- 12224007
TI  - KL-6 as an indicator for lymphocytic interstitial pneumonia (LIP) in a human T
      lymphotrophic virus type 1 (HTLV-1) carrier.
AB  - A 59-year-old woman was admitted to our hospital complaining of a productive
      cough, dyspnea on effort, and low-grade fever. Although chest X-rays showed no
      marked abnormalities, her level of serum KL-6 was extremely high. We therefore
      suspected the presence of interstitial pneumonia. High-resolution computed
      tomography (CT) scan revealed infiltrative shadows in S6 of the right lung, and
      her serum was positive for antihuman T-lymphotropic virus type 1 (HTLV-1)
      antibodies. From the clinical symptoms, radiographic findings, and histological
      findings, the diagnosis was probable lymphocytic interstitial pneumonia (LIP).
      After high-dose corticosteroid therapy, the level of serum KL-6 decreased
      rapidly. We conclude that KL-6 is a convenient and reliable marker for evaluating
      the activity of pulmonary manifestations in HTLV-1 carriers and that it is
      especially useful in monitoring the effectiveness of treatments.

PMID- 12224008
TI  - Treatment with hydroxyurea in thalassemia intermedia with paravertebral
      pseudotumors of extramedullary hematopoiesis.
AB  - Excessive ineffective erythropoiesis in thalassemia intermedia may cause
      paravertebral pseudotumors of extramedullary hematopoiesis. Due to the proximity
      to the spinal canal, these paravertebral masses carry the risk of severe
      neurological damage. Treatment strategies include hypertransfusion, radiotherapy,
      and laminectomy. Hydroxyurea, stimulating fetal hemoglobin synthesis, may
      represent an alternative therapeutic approach. We report on a 26-year-old patient
      suffering from thalassemia intermedia with progressive anemia symptoms and
      presenting multiple intrathoracic paravertebral pseudotumors of extramedullary
      hematopoiesis. Hypertransfusion therapy and splenectomy were followed by regular
      transfusion (baseline hemoglobin 10 g/dl) and chelation with desferrioxamine.
      With this treatment, clinical symptoms disappeared, paravertebral hematopoietic
      masses did not progress, but severe hemosiderosis developed within a few years.
      Hydroxyurea therapy was initiated to increase the efficacy of erythropoiesis,
      thereby reducing the required transfusion volume but suppressing concomitantly
      further expansion of extramedullary hematopoiesis, and finally leading to a
      reduction of transfusional iron load. Treatment was started with 4 mg/kg per day
      and stepwise increased to 12.5 mg/kg per day. The fetal hemoglobin concentration
      increased from 4.5 to 5.5 g/dl after 1 year and to 9.9 g/dl after 2 years of
      treatment. The yearly transfusion volume was halved during the 1st year of
      treatment. At present, after 26 months of treatment, the patient has been
      transfusion-independent for 10 months. Serum ferritin levels decreased from 2844
      to 1335 ng/ml. Size and shape of paravertebral hematopoietic pseudotumors
      remained stable. No side effects of hydroxyurea have been observed. In
      thalassemia intermedia patients with extramedullary hematopoiesis, hydroxyurea
      may lead to independence from regular transfusion therapy without further
      expansion of ectopic hematopoietic tissue.

PMID- 12224009
TI  - Adenovirus-mediated VEGF(165) gene transfer enhances wound healing by promoting
      angiogenesis in CD1 diabetic mice.
AB  - It has been previously shown that vascular endothelial growth factor (VEGF) plays
      a central role in promoting angiogenesis during wound repair and that healing
      impaired diabetic mice show decreased VEGF expression levels. In order to
      investigate the potential benefits of gene therapy with growth factors on wound
      repair, a replication-deficient recombinant adenovirus vector carrying the human
      VEGF(165) gene (AdCMV.VEGF(165)) was topically applied on excisional wounds of
      streptozotocin-induced diabetic mice. Treatment with AdCMV.VEGF(165)
      significantly accelerated wound closure when compared with AdCMV.LacZ-treated, as
      well as saline-treated control mice, by promoting angiogenesis at the site of
      injury. Our findings suggest that AdCMV.VEGF(165) may be regarded as a
      therapeutic tool for the treatment of diabetic ulcers.

PMID- 12224010
TI  - Durable and stratum-specific gene expression in epidermis.
AB  - A number of genetic disorders are manifested in cutaneous epithelium and gene
      therapy approaches for treatment of such diseases are being considered. A
      successful gene therapy protocol requires durable and correctly targeted gene
      expression within the tissue. The continuous renewal and high levels of
      compartmentalization in epidermis are two challenges for a successful gene
      therapy of skin disorders. For those disorders which affect the upper layers of
      epidermis, vectors must be available that target stem cells, but remain silent
      until the progeny of these cells undergo differentiation. To explore the
      potential of long-term and targeted vector expression in epidermis, a hybrid
      retroviral vector encoding the reporter enhanced green fluorescent protein (EGFP)
      was constructed. The viral enhancer in the long terminal repeat of the vector was
      replaced with a 510-bp enhancer element of the human involucrin promoter.
      Keratinocyte-specific expression directed by the hybrid vector was demonstrated
      in culture and suprabasal-specific expression was observed in organotypic human
      epidermal cultures. In vivo transduction of mouse skin with this hybrid vector
      indicated long-term and stratum-specific expression of the transgene in mouse
      epidermis. The design of similar vectors for various gene therapy applications
      constitutes an important step toward clinically effective gene therapy.

PMID- 12224011
TI  - Electromobility of plasmid DNA in tumor tissues during electric field-mediated
      gene delivery.
AB  - Interstitial transport is a crucial step in plasmid DNA-based gene therapy.
      However, interstitial diffusion of large nucleic acids is prohibitively slow.
      Therefore, we proposed to facilitate interstitial transport of DNA via pulsed
      electric fields. To test the feasibility of this approach to gene delivery, we
      developed an ex vivo technique to quantify the magnitude of DNA movement due to
      pulsed electric fields in two tumor tissues: B16.F10 (a mouse melanoma) and 4T1
      (a mouse mammary carcinoma). When the pulse duration and strength were 50 ms and
      233 V/cm, respectively, we found that the average plasmid DNA movements per 10
      pulses were 1.47 microm and 0.35 microm in B16.F10 and 4T1 tumors, respectively.
      The average plasmid DNA movements could be approximately tripled, ie to reach
      3.69 microm and 1.01 microm, respectively, when the pulse strength was increased
      to 465 V/cm. The plasmid DNA mobility was correlated with the tumor collagen
      content, which was approximately eight times greater in 4T1 than in B16.F10
      tumors. These data suggest that electric field can be a powerful driving force
      for improving interstitial transport of DNA during gene delivery.

PMID- 12224012
TI  - Evaluation of Tet-on system to avoid transgene down-regulation in ex vivo gene
      transfer to the CNS.
AB  - Ex vivo gene transfer to the CNS has so far been hampered by instability of
      transgene expression. To avoid the phenomenon of transgene down-regulation, we
      have employed strong, constitutive promoters and compared this expression system
      with the inducible Tet expression system incorporated in a single plasmid vector
      or in lentiviral vectors. Plasmid-based transgene expression directed by the
      constitutive, human ubiquitin promoter, UbC, was stable in transfected HiB5 cells
      in vitro and comparable in strength to the CMV promoter. However, after
      transplantation of UbC and CMV HiB5 clones to the rat striatum, silencing of the
      transgene occurred in most cells soon after implantation of transfected cells.
      The Tet-on elements were incorporated in a single plasmid vector and inducible
      HiB5 clones were generated. Inducible clones displayed varying basal expression
      activity, which could not be ascribed to an effect of cis-elements in the vector,
      but rather was due, at least in part, to intrinsic activity of the minimal
      promoter. Basal expression activity could be blocked in a majority of cells by
      stable expressing the transrepressor tTS. Fully induced expression levels were
      comparable to CMV and UbC promoters. Similar to the constitutive promoters
      transgene expression was down-regulated soon after grafting of inducible HiB5
      clones to the rat striatum. Lentiviral vectors can direct long-term stable in
      vivo transgene expression. To take advantage of this quality of the lentiviral
      vector, the Tet-on elements were incorporated in two lentiviral transfer vectors
      followed by transduction of Hib5 cells. Interestingly, all HiB5 clones
      established by lentiviral transduction showed very similar expression patterns
      and tight regulatability that apparently was independent of transgene copy number
      and integration site. Nevertheless, transgene expression in all lentiviral HiB5
      clones was down-regulated shortly after transplantation to the rat striatum.
      These results confirm the general phenomenon of transgene down-regulation.
      Moreover, the results suggest that the considerable advantages offered by
      lentiviral vectors for direct gene delivery cannot necessarily be transferred
      directly to ex vivo gene delivery. This emphasizes the need for alternative
      vector strategies for ex vivo gene transfer.

PMID- 12224013
TI  - Novel membrane-bound GM-CSF vaccines for the treatment of cancer: generation and
      evaluation of mbGM-CSF mouse B16F10 melanoma cell vaccine.
AB  - Cancer vaccines composed of tumor cells engineered to secrete granulocyte
      macrophage colony-stimulating factor (GM-CSF) are currently being clinically
      evaluated. To enhance the immunogenicity of GM-CSF-secreting tumor cell vaccines,
      a novel approach expressing GM-CSF as a membrane-bound form (mbGM-CSF) on the
      tumor cell surface was investigated. The intent was to enhance antigen
      presentation by increasing interactions between the tumor cell lines in the
      vaccine and GM-CSF receptor positive antigen presenting cells (APC), notably the
      patient's Langerhans cells residing within the intradermal injection site.
      B16.F10 cells engineered to express either membrane-bound or secreted GM-CSF were
      compared in the B16.F10 mouse melanoma model. We observed that mbGM-CSF on the
      tumor cell surface retarded growth and induced protective immunity to subsequent
      wild-type tumor challenge more effectively than tumor cells secreting GM-CSF.
      Vaccination with irradiated mbGM-CSF B16.F10 also provided strong protection from
      wild-type tumor challenge, improved therapeutic effects against established
      tumors, and retarded lung metastases. These results demonstrate that mbGM-CSF
      B16.F10 cells can induce strong systemic immunity that protects against and
      therapeutically treats B16.F10 melanoma more effectively than analogous vaccines
      containing only secreted GM-CSF. These data warrant further development and
      clinical testing of mbGM-CSF tumor cell vaccines.

PMID- 12224014
TI  - Optimisation of real-time quantitative RT-PCR for the evaluation of non-viral
      mediated gene transfer to the airways.
AB  - Naked plasmid DNA and DNA/liposome complexes are currently being considered as
      gene therapy treatments for cystic fibrosis (CF) pulmonary disease. Current
      methods of gene delivery to the airways result only in transient correction of
      the CF ion transport defect, and disease treatment is likely to require repeated
      administrations of vector. However, it is unclear if repeat administration will
      be tolerated by CF individuals. Technologies including TaqMan (Applied
      Biosystems) real-time quantitative reverse transcription-polymerase chain
      reaction (RT-PCR) can be used to determine the efficacy of gene transfer
      formulations. TaqMan RT-PCR assays were designed and optimised to detect plasmid
      vector-derived and endogenous gene expression. Subsequently, these assays were
      used to quantify vector-derived mRNA after delivery of naked DNA and DNA/liposome
      formulations expressing human and murine cystic fibrosis transmembrane
      conductance regulator (CFTR) to the mouse airways. Vector-derived mRNA was
      detected in samples following the delivery of naked DNA or DNA/liposomes to the
      mouse airways, and no reduction in vector-derived mRNA was observed upon repeat
      administration, a finding that is consistent with the murine and human CFTR being
      tolerated by the mouse. Although it remains to be seen if CF patients can
      tolerate long-term expression of wild-type CFTR, these data demonstrate that
      TaqMan RT-PCR is an effective tool to accurately quantify transgene expression in
      the airways.

PMID- 12224015
TI  - Electrically mediated delivery of vector plasmid DNA elicits an antitumor effect.
AB  - In vivo electroporation is an efficient means of increasing plasmid DNA delivery
      to normal tissues, such as skin and muscle, as well as directly to tumors. In the
      experiments described here, plasmid DNA was delivered by in vivo electroporation
      to B16 mouse melanomas using two very different pulsing protocols. Reporter
      expression increased 21- or 42-fold, respectively with electroporation over
      injection alone. The growth of experimental melanomas with an approximate
      diameter of 4 mm on the day of treatment was monitored after electroporation
      delivery of reporter plasmid DNA. Remarkably, short-term complete regressions
      using one of these pulsing protocols occurred in up to 100% of mice. These
      regressions continued long term in up to 83% of animals. 70% of these mice were
      resistant to challenge with B16 melanoma cells. Histological analysis revealed
      large numbers of apoptotic cells 24 h after treatment. This antitumor effect did
      not require therapeutic cDNA expression or eukaryotic sequences.

PMID- 12224016
TI  - Human foamy virus integrase fails to catalyse the integration of a circular DNA
      molecule containing an LTR junction sequence.
AB  - The presence of closed circular forms of the linear DNA genome of human foamy
      virus (HFV) has not been established. The ability of the HFV integrase (IN) to
      catalyse the integration of these circular forms (termed 2 long terminal repeat
      (LTR) circles) was investigated, with a view to producing a novel hybrid vector.
      To this end, a construct was made containing, in addition to the enhanced green
      fluorescent protein (eGFP) marker gene, the last 27 bp of the 3' U5 LTR region of
      HFV fused to the first 28 bp of the 5' U3 LTR, the latter representing a 2LTR
      circle. Marker gene expression following transfection of both 293 and 293T cells
      indicated that the level of integration was not significantly increased by the
      HFV IN. Moreover, correctly integrated provirus-like forms of the input plasmid
      could not be detected by PCR. Taken together, these results show that the HFV IN
      is not able to integrate a circular molecule containing an LTR junction and,
      hence, the technique is not exploitable as a tool to produce hybrid vectors for
      gene therapy.

PMID- 12224017
TI  - Viral and non-viral gene therapy partially prevents experimental cisplatin
      induced neuropathy.
AB  - Sensory neuropathies are a frequent and dose-limiting complication resulting from
      treatment with cisplatin. Neurotrophin-3 (NT-3) promotes the survival of the
      large fiber sensory neurones that are impaired in cisplatin-induced neuropathy,
      and may therefore serve as a preventive agent. However, the short half-life of
      recombinant NT-3 after systemic administration limits its clinical applications.
      We compared two muscle-based gene transfer strategies for the continuous delivery
      of NT-3 to the bloodstream in an experimental model of cisplatin-induced
      neuropathy. Electrophysiological studies showed that the intramuscular injection
      of an adenovirus encoding NT-3 partially prevented the cisplatin-induced increase
      in sensory distal latencies. Similar effects were observed in cisplatin-treated
      mice that received intramuscular injections of a plasmid encoding NT-3 associated
      with in vivo electroporation. The two techniques were well tolerated and induced
      only slight muscle toxicity. Measurement of renal function, weight and survival
      showed that neither technique increased the toxicity of cisplatin. Our study
      shows that gene therapy, using either a viral or a non-viral vector, is a
      promising strategy for the prevention of cisplatin-induced neuropathy.

PMID- 12224018
TI  - Combined effects on tumor growth and metastasis by anti-estrogenic and
      antiangiogenic therapies in MMTV-neu mice.
AB  - Breast tumor growth and metastasization are both hormone-sensitive and
      angiogenesis-dependent. Recent work carried out in our laboratory on a transgenic
      model of breast cancer displaying many similarities to its human counterpart, has
      shown that liposome-mediated angiostatin cDNA delivery partially inhibits both
      local and metastatic growth. However, it is now recognized that anti-angiogenesis
      strategy alone cannot completely arrest tumor growth and spread, and this led to
      the suggestion that approaches based on different molecular mechanisms could
      usefully be combined. In the present work, we investigated whether tamoxifen, a
      classical antiestrogen agent widely used in human therapy, could improve the
      results obtained with angiostatin alone. Further reduction of local growth was
      achieved with the combined regimen with respect to angiostatin or tamoxifen
      alone, while, as expected, no metastatic growth was detected in either group. We
      therefore conclude that a combination of angiogenesis inhibitors with
      antiestrogen drugs might be useful in humans and that other associations between
      conventional and gene transfer-mediated therapy are worth investigating and will
      soon become important components of anticancer therapy.

PMID- 12224019
TI  - Intraperitoneal injection of adenovirus-mediated NK4 gene suppresses peritoneal
      dissemination of pancreatic cancer cell line AsPC-1 in nude mice.
AB  - NK4, composed of the N-terminal hairpin and subsequent four-kringle domains of
      hepatocyte growth factor (HGF), acts not only as a competitive antagonist for HGF
      but also as a potent angiogenesis inhibitor. This study was designed to assess a
      therapeutic potential of adenovirus-mediated NK4 gene transfer for disseminated
      pancreatic cancer cells in the peritoneal lavage of nude mice. We constructed a
      recombinant adenovirus NK4 (Ad-NK4), which encodes a secretable form of human
      NK4. In vitro migration of AsPC-1 (human pancreatic cancer cell line) was
      stimulated by HGF, and it was completely inhibited by Ad-NK4 transfection. Weekly
      intraperitoneal injections of Ad-NK4 could suppress the development of tumor
      nodules in a nude mouse peritoneal dissemination model. NK4 expression was
      detected in the disseminated nodules, liver, pancreas, spleen, and mesenterium.
      Immunohistochemical study of the disseminated tumors showed a remarkable decrease
      in microvessel density and an increase in number of apoptotic tumor cells in the
      Ad-NK4-treated mice. Survival of the Ad-NK4-treated mice was significantly
      improved. This study indicates that the intraperitoneal transduction of
      adenovirus-mediated NK4 gene may be a useful therapeutic modality to prevent the
      development of peritoneal dissemination of pancreatic cancer.

PMID- 12224020
TI  - p53 alone or in combination with antisense cyclin D1 induces apoptosis and
      reduces tumor size in human melanoma.
AB  - Melanoma incidence is growing at a faster rate than any other human malignancy.
      Wild-type (wt) p53 is important in both G(1) and G(2) cell cycle arrest, and
      cyclin D1 (CD1) is necessary for G(1)-->S progression in melanoma cells. We
      reported that an adenoviral vector containing wt p53 significantly reduced
      [(3)H]thymidine uptake in melanoma cells containing mutant but not wt p53.
      Subsequently we showed that CD1 decreased melanoma proliferation and increased
      apoptosis. We now extend these findings by evaluating the effect on preformed
      melanomas of (1) intratumoral therapy with wt p53 alone, (2) wt p53 in
      combination with antisense (AS) CD1, both short (< or =14 days) and longer term,
      and (3) doubling the dose or repeat doses of wt p53 or AS CD1. Two melanoma cells
      lines that metastasize in SCID mice (451 and 1205) were used, one containing a
      p53 mutation (451) and the other a normal p53 gene sequence (1205). Compared to
      injection with a control adenoviral vector containing beta-galactosidase (LacZ),
      intratumoral injection of wt p53 slowed the growth of tumors formed from 451
      cells. Using 5 x 10(8) plaque forming units as our standard intratumoral dose,
      neither doubling the dose of LacZ, p53 or AS CD1, nor repeat doses of the
      vectors, was as effective as combined therapy with wt p53+AS CD1, which resulted
      in the shrinkage of all tumors treated and 4/7 (57%) tumors vanished. No tumors
      treated with wt p53 or AS CD1 alone vanished. Wt p53+AS CD1 treatment resulted in
      significantly more cells undergoing apoptosis compared to either therapy alone.
      In summary, combining the separately effective treatment vectors p53 and AS CD1
      led to an enhanced growth-suppressive and apoptotic effect, supporting a role for
      combination gene therapy to treat human malignant melanoma.

PMID- 12224021
TI  - Salmonella pathogenicity island-2 and anticancer activity in mice.
AB  - Salmonella enterica servovar Typhimurium is capable of targeting, colonizing, and
      eliciting growth suppression of tumors in mice. We examined the effects of
      mutations on this anticancer phenotype in two Salmonella virulence gene clusters.
      Salmonella pathogenicity island (SPI)-1 genes promote systemic invasion from the
      intestine, whereas SPI-2 genes support systemic survival within macrophages and
      other cells. Disabling SPI-1 (prgH(-)) strongly reduced invasion in vitro, but
      had no effect on tumor growth suppression in vivo. However, disabling SPI-2
      (ssaT(-)) ablated tumor growth suppression. In addition to ssaT(-), mutations in
      SPI-2 genes sseA, sseB, sseC, sscA, and ssrA also eliminated antitumor activity,
      whereas mutations in sseF or sseG yielded partial loss of function. Impaired
      tumor amplification was seen in three SPI-2 mutants tested after intravenous or
      intratumoral injection. A SPI-2(-) strain was unable to suppress tumor growth in
      CD18-deficient mice with defective macrophages and neutrophils, suggesting that
      loss of tumor growth suppression in wild-type mice by SPI-2 mutants was not
      solely a function of increased susceptibility to immune attack. Thus, SPI-2 is
      essential for the Salmonella antitumor effects, perhaps by aiding bacterial
      amplification within tumors, and is the first identified genetic system for this
      Salmonella phenotype.

PMID- 12224023
TI  - Cationic liposomes conjugation to recombinant adenoviral vectors containing
      herpes simplex virus thymidine kinase gene followed by ganciclovir treatment
      reduces viral antigenicity and maintains antitumor activity in mouse experimental
      glioma models.
AB  - Gene therapy using adenoviral (Ad) vector containing herpes simplex virus
      thymidine kinase (AxCAHSV-tk) followed by the administration of ganciclovir (GCV)
      has been a promising therapy for cancer including malignant gliomas. However,
      there remain numerous problems to overcome, such as the high immunogenicity and
      toxicity of Ad vector. To optimize the therapy, we investigated whether a
      conjugation of our original cationic liposomes and Ad vectors reduces viral
      antigenicity and maintains the antitumor activity in mouse experimental
      (subcutaneous and intracranial) glioma models. Our original liposomes consist of
      N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride, dilauroyl
      phosphatidylcholine, and dioleoyl phosphatidyl-ethanolamine in a molar ratio of
      1:2:2. AxCAHSV-tk and GCV showed a remarkable inhibition of experimental glioma
      growth. The growth-inhibitory effect decreased in mice previously immunized with
      another Ad vector (AxCALacZ). In contrast, the conjugation of AxCAHSV-tk and
      liposomes did not diminish the growth-inhibitory effect. Furthermore, the
      conjugation reduced antigenicity for Ad vector in vivo. These findings suggest
      that suicide gene therapy, using a conjugation of AxCAHSV-tk and our liposomes,
      is a feasible approach for human cancer gene therapy, especially malignant
      gliomas.

PMID- 12224022
TI  - Adenovirus-mediated combined P16 gene and GM-CSF gene therapy for the treatment
      of established tumor and induction of antitumor immunity.
AB  - Antitumor effects of combined transfer of P16 and cytokine genes were
      investigated in this study. The adenovirus harboring the P16 gene (AdP16) and
      murine granulocyte-macrophage colony-stimulating factor gene (AdGM-CSF) were
      utilized for the treatment of established tumors. The mice were inoculated
      subcutaneously with Renca cells and, 6 days later, received an intratumoral
      injection of AdP16 in the presence or absence of AdGM-CSF. The results
      demonstrated that tumor-bearing mice treated with AdP16 in combination with AdGM
      CSF showed more potent inhibition of tumor growth and survived much longer than
      did mice treated with AdP16, AdGM-CSF, adenovirus expressing beta-galactosidase,
      or phosphate-buffered saline alone (P<.01). The tumor mass showed obvious
      necrosis and inflammatory cell infiltration, and more CD(4)(+) and CD(8)(+) T
      cells infiltrating the tumor after combined therapy. After combined therapy, the
      expression of MHC-1 (H-2K(d)) and Fas molecules on freshly isolated tumor cells
      increased greatly. The activity of specific cytotoxic T lymphocytes was also
      found to be induced more significantly after the combined therapy (P<.01). Our
      results demonstrated that combined therapy with P16 and GM-CSF genes can inhibit
      the growth of established tumors in mice significantly and induce antitumor
      immunity of the host efficiently.

PMID- 12224024
TI  - Growth suppression by a p14(ARF) exon 1beta adenovirus in human tumor cell lines
      of varying p53 and Rb status.
AB  - We have analyzed the ability of an adenoviral vector encoding the exon 1beta
      region of the p14(ARF) tumor suppressor (ARF) to suppress the growth and
      viability of an array of tumor cell lines of various origins and varying p53 and
      Rb status, in order to establish the clinical potential of ARF. An important
      activity of ARF is regulation of p53 stability and function through binding to
      the mdm2 protein. By sequestering mdm2, ARF may promote growth suppression
      through the Rb pathway as well because mdm2 can bind to Rb and attenuate its
      function. Whereas the high frequency of ARF gene deletion in human cancers,
      accounting for some 40% of cancers overall, suggests that ARF would be a strong
      candidate for therapeutic application, the possible dependence of ARF activity on
      p53 and Rb function presents a potential limitation to its application, as these
      functions are often impaired in cancer. We show here that a replication-defective
      adenovirus, Ad1beta, encoding the exon 1beta region of ARF is most effective in
      tumor cells expressing endogenous wild-type p53. Nevertheless, Ad1beta suppresses
      tumor cell growth and viability in vitro and in vivo, inducing G1 or G2 cell
      cycle arrest and cell death even in tumor cells lacking both functional Rb and
      p53 pathways, and independently of induction of the p53 downstream targets, p21,
      bax, and mdm2. These results point to an activity of ARF in human tumor cells
      that is independent of Rb or p53, and suggest that therapeutic applications based
      on ARF would have a broad clinical application in cancer.

PMID- 12224025
TI  - Combined radiation and gene therapy for brain tumors with adenovirus-mediated
      transfer of cytosine deaminase and uracil phosphoribosyltransferase genes.
AB  - Radiation therapy is an established modality for the treatment of malignant
      gliomas. Several reports have shown the advantage of additional radiation in
      combination with gene therapy. In this study, we investigated the ability of
      radiation therapy to enhance 5-fluorocytosine (5-FC)/cytosine deaminase (CD) plus
      uracil phosphoribosyltransferase (UPRT) gene therapy in malignant gliomas. In
      vitro study suggested evidence of a significant cytotoxic interaction between
      radiation therapy and 5-FC/CD + UPRT gene therapy for glioma cells. In vivo
      experiments demonstrated that the combination of gene therapy and radiation
      possessed superior antitumor effect in comparison to single therapy. However, the
      adverse effects of radiation therapy in combination with the gene therapy were
      observed with respect to normal brain. This combination therapy may be feasible
      for the treatment of gliomas, although the radiation dose and area should be
      reduced in order to prevent side effects.

PMID- 12224026
TI  - In vitro activation of cancer patient-derived dendritic cells by tumor cells
      genetically modified to express CD154.
AB  - PURPOSE: Triggering of CD40 on antigen-presenting cells via its ligand CD154 is
      an important event in the initial phase of an immune response against cancer
      cells. In this study, we investigated the effects of adenoviral CD154
      immunomodulatory gene therapy on the activation of human dendritic cells (DCs) in
      a well-defined in vitro system. EXPERIMENTAL DESIGN: Human bladder cancer cell
      lines and tumor cells from patients with renal cell carcinoma (RCC) were
      transduced with Ad-CD154 vectors or control vectors. Activation of human in vitro
      generated DCs after coculture with transduced tumor cells was analyzed.
      Therapeutic efficacy and cytotoxic T-lymphocyte (CTL) activity were assessed in a
      subcutaneous (s.c.) murine bladder cancer model. RESULTS: Human bladder cancer
      cell lines expressing CD154 showed a decreased growth rate, increased apoptosis,
      and modulated expression of molecules important for recognition by cytotoxic
      lymphocytes. Further, CD154-expressing allogeneic bladder tumor cell lines and
      autologous tumor cells from patients with renal cell cancer induced maturation of
      DCs and stimulated IFN-gamma production from lymphocytes cocultured with mature
      DCs. In vivo studies showed that CD154 gene therapy was highly effective in wild
      type mice but only minimally effective in nude mice. Consequently, strong tumor
      specific CTL activity was detected in mice vaccinated with tumor cells expressing
      CD154. CONCLUSIONS: Using tumor cell lines as well as patient-derived material,
      we could show that tumor cells expressing CD154 efficiently induce maturation and
      activation of DCs as well as activation of lymphocytes. Our murine in vivo
      studies demonstrate that lymphocytes contribute to the observed antitumor effect
      in a s.c. bladder tumor model. These studies should stimulate CD154 gene therapy
      approaches for the treatment of urologic malignancies.

PMID- 12224027
TI  - Procathepsin D in breast cancer: what do we know? Effects of ribozymes and other
      inhibitors.
AB  - Procathepsin D (pCD) is a major secreted glycoprotein in some human breast and
      other cancer cell lines. Several groups proposed that pCD served as a growth
      factor for these cell lines. Secreted pCD has been demonstrated in tissue
      section, tissue culture supernatants, carcinoma cytosols, and nipple aspirates.
      Moreover, several clinical studies suggested a potential role for this molecule
      in metastasis because its concentration in primary tumors correlated with an
      increased incidence of tumor metastases. In this paper, the effects of pCD were
      evaluated by proliferation in vitro and by mouse studies in vivo. Subsequent flow
      cytometry experiments showed the specificity of pCD binding to cancer cells. Cell
      cultivation showed that addition of either pCD or its activation peptide
      stimulates growth of cancer cells. These effects can be inhibited both in vitro
      and in vivo by anti-pCD antibodies. In addition, production of pCD can be
      inhibited by specifically designed ribozymes. This paper is focused on mitogenic
      effects of pCD, which seem to involve interaction of the activation peptide with
      as yet unidentified receptor. Different mechanisms by which pCD could promote
      development and spread of cancer cells are discussed.

PMID- 12224028
TI  - A tandemly repeated thyroglobulin core promoter has potential to enhance efficacy
      for tissue-specific gene therapy for thyroid carcinomas.
AB  - Recombinant adenoviruses, carrying herpes simplex virus thymidine kinase (HSVtk)
      genes, were developed to evaluate the possibility of tissue-specific gene therapy
      for thyroid carcinomas. The HSVtk gene was driven by a minimal thyroglobulin (TG)
      promoter (AdTGtk) and a tandemly repeated minimal TG promoter (Ad2 x TGtk) to
      obtain thyroid-specific cell killing ability. The transduction of HSVtk genes by
      infection with Ad2 x TGtk followed by ganciclovir (GCV) treatment showed more
      powerful cytotoxicity for TG-producing FRTL5 cells, a rat normal thyroid cell
      line, and FTC-133 cells, a human follicular thyroid carcinoma cell line, than
      when infected with AdTGtk in vitro. The cell killing ability of Ad2 x TGtk was 10
      to 30-fold higher than that of AdTGtk and similar to that of AdCMVtk, which
      carries HSVtk under the control of CMV promoter. Whereas after treatment with
      adenovirus/GCV to non-TG-producing cell lines (undifferentiated thyroid carcinoma
      cell lines and carcinoma cell lines from other tissues), Ad2 x TGtk and AdTGtk
      needed more than 100-fold concentrated GCV to reach IC(50) compared to AdCMVtk.
      We confirmed the enhanced efficacy of Ad2 x TGtk for tissue-specific cytotoxicity
      in vivo. After adenovirus/GCV treatment for FTC-133 tumor-bearing nude mice, Ad2
      x TGtk enhanced tumor growth inhibition and survival rates compared to AdTGtk.
      Tumor growth inhibition and survival rates by Ad2 x TGtk were similar to that by
      AdCMVtk. Moreover, any toxic effect for rat normal tissues was not revealed after
      intravenous injections with Ad2 x TGtk and intraperitoneal administrations with
      GCV in vivo, whereas severe liver damages were observed after treatment with
      AdCMVtk/GCV. These data indicate a beneficial effect of Ad2 x TGtk for tissue
      specific gene therapy for TG-producing thyroid carcinomas without toxicity for
      normal tissues.

PMID- 12224029
TI  - [Diagnostic and therapeutical considerations in the treatment of giant
      aneurysms].
AB  - The treatment of giant aneurysms requires a thorough surgical and endovascular
      planning as this entity is accompanied by complex vascular and blood flow
      particularities. Even in experienced neurovascular centers the clinical outcome
      varies considerably. Within a series of 1386 aneurysm patients 72 (5%) giant (>25
      mm) aneurysms were treated in our institution. Their age ranged between 26 and 81
      years (medium age 52 years). 22 patients were suffering of a subarachnoid
      hemorrhage (SAH). Additionally there were 50 patients with nerve palsies or
      unspecific symptoms due to unruptured giant aneurysms (UGA). Treatment modalities
      included surgical clipping (n = 35), balloon occlusion of the ICA (n = 12),
      endovascular coiling (n = 7) or a combined regimen of balloon occlusion, surgical
      clipping and EC-IC bypass (n = 8). 10 patients could not be treated on due to
      their high age or minor clinical status (H&H IV and V). 6 of 15 (40%) SAH
      patients were discharged without any complaints compared to 26% (12 of 47
      patients) in the group of unruptured aneurysms. 1 SAH-patients (7%) versus 13 UGA
      (28%) patients suffered persisting nerve palsies or minor neurological disorders.
      32% (n = 15) of the UGA-patients were suffering of major neurological deficits
      and required further professional help. 5 patients remained in a vegetative
      state, 3 of these had been admitted with an incidental finding of an UGA. 6 of 15
      (40%) SAH-patients died, 5 of them admitted with H&H grade IV or V. However only
      3 of 47 (6%) UGA patients died. 2 of these had a fatal SAH before treatment, 1
      underwent EC-IC bypass surgery with insufficient hemispheric vascularization
      followed by gross infarction. The clinical status and age of the patient are
      significant factors influencing treatment associated morbidity and mortality. The
      individual vascular situation may lead to a complex therapeutical regimen thereby
      predisposes higher complication rates. We believe that surgical clipping is the
      first choice of treatment allowing temporarily clipping and reconstruction of the
      normal anatomy by shrinking or/and reconstructive clipping while reducing the
      mass effect. Whereas endovascular coiling alone is less favorable due to the
      packing of the coils a combined endovascular and surgical approach have to be
      considered in selected cases.

PMID- 12224030
TI  - Long term results of radiosurgery for vestibular schwannomas.
AB  - Radiosurgery is either a primary or an adjunct management approach used to treat
      patients with vestibular schwannomas. The goals are long-term tumour growth
      control, maintenance of cranial nerve function and prevention of new neurologic
      deficiencies. We sought to determine long-term outcomes measuring the potential
      benefits against the neurological risks of radiosurgery. METHODS: 278 patients
      with vestibular schwannomas underwent Gamma Knife radiosurgery as a treatment
      modality for from April 1992 to November 2001. The long-term results of 60
      patients were evaluated who received radiosurgery as primary treatment. 12 cases
      presented with previously performed subtotal microsurgical resection or
      recurrence of disease (12-96 months, median 39). The median treatment volume was
      3.8 ccm and the median dose to the tumour margin was 12 Gy. The median patient
      follow-up time was 88 months (range 72-114 months). RESULTS: Four tumours
      progressed after primary radiosurgery. Tumour control rate was 93%. Useful
      hearing (Gardner-Robertson I/II) was preserved in 16 patients (55%). Clinical
      neurological improvement occurred in 36 patients (60%). Adverse effects comprised
      neurological symptoms (incomplete facial palsy) (House-Brackman II/III) in five
      cases (three recovered completely), mild trigeminal neuropathy in three cases,
      and morphological changes displaying rapid enlargement of preexisting macrocysts
      in two patients and tumour growth in two other ones. Microsurgical resection was
      performed in three cases (5%) and one patient underwent a shunting procedure
      because of hydrocephalus formation. In patients who had undergone previous
      microsurgery, neither new cranial nerve deficit nor any tumour growth was
      observed. CONCLUSIONS: Radiosurgery performed with current techniques proved to
      be an effective method for growth control of vestibular schwannomas with both a
      low mortality rate and a good quality of life. An increasing percentage of
      patients will undergo radiosurgery as accessibility to this alternative
      increases, and more data regarding long-term follow-up are available. It is a
      post-operative complementary treatment for partially removed tumours.
      Accordingly, radiosurgery is a useful method for the management of properly
      selected patients.

PMID- 12224031
TI  - Results for microsurgical removal of tentorial meningiomas.
AB  - OBJECTIVE: Growth patterns of tentorial meningiomas are related to the deep
      cerebral venous system and to cranial nerves IV-XI. Localization and surgical
      aggressiveness are decisive for the outcome to be expected. PATIENTS AND METHODS:
      n = 25 patients (22 f, 3 m), aged from 26-77 (mean: 56.4) years underwent
      microsurgical removal of their tentorial meningioma. Tumor size was as follows: n
      = 11 < 3 cm, n = 6 3-5 cm, n = 8 > 5 cm. The median of the preoperative Karnofsky
      scores was 90. The operative approaches chosen were suboccipital in n = 14,
      subtemporal in n = 6, occasionally a combined supra- and infratentorial approach
      was chosen. Data regarding surgery, histology and postoperative course were
      available through the patient's charts and through outpatient clinic. RESULTS: n
      = 20 (80%) of the tumors were rated WHO grade I, n = 5 (20%) WHO grade II. Tumor
      removal according to Simpson was degrees I in n = 9 (36%), degrees II in n = 14
      (56%), degrees III in n = 2 (8%). Mortality was 0%. In n = 6 patients (24%)
      neurological worsening, mainly due to transient cranial nerve deficits was noted.
      Surgical complications (CSF fistula, wound healing problems) occurred in n = 5
      patients (20%). The median of the postoperative Karnofsky scores on last follow
      up was 90 after a median of 41.9 months. Two patients (8%), one of whom underwent
      reoperation developed tumor recurrency during follow up. CONCLUSIONS:
      Neurological deficits following microsurgical removal of tentorial meningiomas
      are transient in the majority of patients. The apparently high rate of incomplete
      tumor resection (app. 60% Simpson grades II and III) is due to the close
      topographical relationship of these tumors with important neurovascular
      structures. Thus, the operative strategy should not be excessively aggressive,
      but rather take into account the option to observe residual tumor or to apply
      additional stereotactic convergent beam radiation in selected cases.

PMID- 12224032
TI  - MRI- and skull x-ray-based approaches to evaluate the position of deep brain
      stimulation electrode contacts--a technical note.
AB  - Deep brain stimulation (DBS) has developed into an established therapy for the
      treatment of movement disorders, most commonly Parkinson's disease and tremor of
      different etiology. The subthalamic nucleus (STN) has evolved as the preferred
      target for DBS in patients with idiopathic Parkinson's disease. The principal
      target for DBS in tremor patients is the ventrolateral thalamus which has been
      explored for ablative procedures (thalamotomy) for some decades. Detailed
      information about the exact site of chronic stimulation, i.e. the location of the
      active electrode contacts, are important to map the actual subcortical structures
      modulating the therapeutic effects of DBS. We compared two different methods not
      requiring intra-operative teleradiography to determine the stereotactic
      coordinates of single electrode contacts, (i) correlation of pre- and post
      operative MRI, and (ii) post-operative stereotactic skull x-ray. For seven
      patients implanted bilateral with quadripolar DBS electrodes the coordinates for
      each contact were determined by both approaches. This revealed for a total of 56
      electrode contacts a median euclidean 3D-difference between both methods of 1.18
      mm (range 0.42 to 1.93 mm). These data suggest that both approaches may be used
      to determine the position of single electrode contacts.

PMID- 12224033
TI  - [Recommendations for the management of unruptured intracranial aneurysms].
AB  - Optimal management of patients with unruptured intracranial aneurysms (UIAs)
      remains controversial. Recent studies have found conflicting data regarding the
      natural history and the treatment outcome of UIAs. Based on the recommendations
      published by the American Heart Association, the Section of Vascular Neurosurgery
      of the German Society of Neurosurgery has formed a task force to summarize the
      available data and to develop a practical framework for the management of UIAs.
      For UIAs, only evidence from nonrandomized historical cohort comparisons and case
      series without control subjects are available, supporting only grade C
      recommendations (options), but no standards (grade A) and no guidelines (grade
      B). The present recommendations have been developed as a neurosurgical,
      neuroradiological and neurological consensus. They are based on the existing data
      of both treatment risks and the risks of the natural history of UIAs.

PMID- 12224034
TI  - Late neurological deterioration 30 years following conservative treatment of a
      lower cervical spine fracture--a case report.
AB  - A today 44 years old man suffered from a compression and subluxation fracture of
      C 4 and C 5 vertebral body during a swimming accident in 1971. The primary
      therapy was conservative and the patient was rehabilitated. Since 1997 the
      patient showed a slowly progressive right hemiparesis with signs of cervical
      myelopathy. The diagnostic procedures revealed a severe deformity of the cervical
      spine with myelon compression. We performed an operation with replacement of C4
      and C5 and dorsal stabilization at the same time. This very impressive case shows
      the risk of a late and slowly onset of myelopathic deterioration while latent
      bony instability persist post traumatic. The authors think in agreement with the
      actual literature that the early operative stabilization of instable fractures of
      the lower cervical spine is inevitable. According to the grade of neurological
      and bony damage the operation should not be performed later than 8-12 hours after
      injury.

PMID- 12224035
TI  - [Impact Factor 2001: SSCI 1,144].

PMID- 12224036
TI  - [Caregivers' views of the treating psychiatrists: coping resource or additional
      burden?].
AB  - OBJECTIVE: This study aimed at investigating how caregivers of schizophrenic
      patients perceive the contact with mental health professionals and which are the
      key factors for their satisfaction or dissatisfaction. METHOD: 42 in-depth
      interviews were analysed with a view to discover the caregivers' experiences with
      psychiatric treatment. RESULTS: The analysis of the interview data showed three
      fundamental areas in which caregivers perceive the contact with psychiatrists as
      supportive or troublesome: 1. the information about the disease and the
      treatment, 2. the long-term cooperation with the caregivers, and 3. the general
      way of behaving towards the caregivers and the patients. Caregivers' attitudes
      towards psychiatry are strongly influenced by positive and negative experiences
      they have had in these three fields. DISCUSSION: The widespread criticism of
      caregivers is caused by dissatisfaction with central areas of psychiatric
      practice. Optimal treatment and consulting conditions, from the caregivers'
      perspective, can only be approximately achieved. However, psychiatrists,
      patients, and caregivers should stay in close contact in order to meet the needs
      of the caregivers, such as being informed, being taken seriously and being
      involved in the treatment.

PMID- 12224037
TI  - [Housing and work as criteria of the "Social Integration" of the mentally ill -
      development in Germany between 1900 and 2000].
AB  - AIM: This paper analyses, in what way psychiatrists considered housing and work
      as criteria of social integration of mentally ill people and what models of care
      were suggested in Germany throughout the 20th century. METHOD: Publications in 29
      German professional and scientific psychiatric journals through the complete
      period from 1900 to 2000 and monographs were searched for papers on the above
      issues. RESULTS: Until the second half of the century, integrative initiatives
      related to housing and work generated in asylums without the aim of a full social
      integration of the patients. In the activistic concept of NS-psychiatry, work
      became an obligation for patients and a criterion for selection that decided on
      life and death. Not until the late 1950s, there again was an orientation towards
      integration in psychiatric care in both German states. Whilst already in 1963 the
      "Rodewisch Theses" outlined recommendations for the rehabilitation of the
      mentally ill already in the GDR (East Germany), a similar mark of reform ideas
      was published in the "enquete" in the FRG (West Germany) in 1975. In the GDR
      initiatives were limited to a small number of locations. In the FRG and the re
      unified Germany various forms of sheltered housing and work were established -
      also with significant regional variation. However, a clear discussion of
      underlying aims and implications for the structure of mental health care was not
      found in the psychiatric literature. CONCLUSIONS: In the 20th century a tradition
      of psychiatric ideas related to housing and work did not develop in Germany.
      Particularly, there were only sporadic contributions from university psychiatry.
      Work was more frequently explicit subject of discussions than housing. Both areas
      were - slowly and in discontinuity - established as criteria of integration of
      people with mental illnesses, which was increasingly accepted as an aim of mental
      health care.

PMID- 12224038
TI  - [Poverty and deficits in basis social supplies among inpatient psychiatric
      patients].
AB  - OBJECTIVE: People with psychiatric diseases are often afflicted by processes of
      social disintegration and social problems are of great importance for the
      treatment of the mentally ill. METHODS: Two departments of psychiatry and
      psychotherapy with obligatory service for their area - one in an inner city area
      of a large town with disadvantageous social structure, one in a small town with
      more favourable economic data - collected data during a two-months-period in 1998
      according to the social situation of their patients. RESULTS: 38,0 % resp. 31,9 %
      of the patients were living under conditions of poverty; 12,2 % resp. 11,5 % had
      acute housing problems, only 17,3 % resp. 31,7 % had some kind of payed
      occupation. Poverty was defined either as being dependent on public assistance or
      having an income below 50 % of the average. Patients with schizophrenic psychosis
      and patients with substance abuse related disorders formed in both departments
      the main groups and were at the same time those with the lowest income. Patients
      with substance abuse, mainly alcoholics, were more afflicted by social
      disintegration in the inner city area than in the small town sample. Concerning
      schizophrenic disorders, regional differences were not as prominent. CONCLUSIONS:
      The high risk of poverty among the mentally ill has to be taken in account in the
      development of community services, hospital staff and social legislation.

PMID- 12224039
TI  - [Subgroups and Prognosis of "Difficult-to-Place" Schizophrenic Long-Stay
      Patients: Distinguishing "Hard Core" Patients].
AB  - Long-standing processes of deinstitutionalization often display processes of
      selection that result in groups of patients with marked disability profiles left
      in hospital. According to the literature socially deviant and unacceptable
      behaviour are a main obstacle to living in the community. Therefore, a group of
      "remnant" chronic schizophrenic patients was analysed by means of a latent class
      analysis with indicators of social behaviour and compliance. Three different
      subgroups were found, one of which had an extremely poor level of adaptation.
      However, prognosis of staff with regard to patients' ability to live outside the
      psychiatric hospital, and the rates of patients being moved into the community in
      the course of subsequent deinstitutionalization were not different among the
      three groups. Characteristics of "most-difficult-to-place patients' " as
      discussed in the literature are called into question on the basis of the results
      of this study.

PMID- 12224040
TI  - [Subjective quality of life in severely disabled long-stay schizophrenic
      patients].
AB  - In the controversy about severely chronic mental patients, who still reside in
      the psychiatric hospital after decades of deinstitutionalization, their quality
      of life (QoL) has become a main topic. On the basis of a critique of the
      dominant, mere standardized approach to QoL this method is compared with a
      qualitative approach in such a schizophrenic "residual" patient group (n = 144).
      While in the standardized approach a high level of subjective QoL could be found
      that correlated positively with the duration of hospitalisation, the open
      interviews yielded specific experiences of deficiencies. The appraisal of the
      quality of life especially of chronic or hospitalized patients is reconsidered.

PMID- 12224041
TI  - [Gerontopsychiatric consultation service].
AB  - In the discussion of the increasing costs of health care in Germany the frequent
      and often times long inpatient treatments of elderly patients are pointed out.
      Since these patients also suffer from psychiatric disorders very frequently, a
      psychiatric consultation is required rather often. This study was aimed to
      evaluate the requirements of a consultation service for elder inpatients. For
      this purpose all 9363 consultation reports from 1994 to 1998 were evaluated
      retrospectively. 2152 (31.4 %) of the patients visited by the psychiatric
      consultation service were over 64 years old. The most frequent diagnoses were
      organic brain syndrome (ICD-10: F0), particularly senile dementia (ICD-10: F00 -
      03), adjustment disorder (ICD-10: F43) and affective disorders, particularly
      depressive disorders (ICD-10: F3). In 139 patients (6,5 %) a consultation was
      requested because of a suicidal attempt prior to admission. Our results suggest
      that in a gerontopsychiatric consultation service predominantly old patients with
      internal diseases and with the need of psychosocial help are visited and that the
      specific knowledge of psychopharmacological treatment in multimorbid patients as
      well as the psychosocial help and legal advice is requested. These aspects should
      therefore be a special focus in educational programs for a gerontopsychiatric
      consultation service.

PMID- 12224042
TI  - [Improvement of tardive dyskinesia after treatment with olanzapine].
AB  - Tardive dyskinesia is a severe complication of neuroleptic treatment. It may
      develop weeks, even years after starting a neuroleptic treatment and the symptoms
      may be irreversible. Neuroleptic compounds are not only used in cases of
      schizophrenia, but also in cases of severe depression with delusional symptoms.
      We want to present the case of a 67 year old female patient who developed
      haloperidol induced dyskinesea and stress unto the successful treatment of this
      complication with olanzapine in combination with paroxetine. Under this regime
      not only the improvement of the depression, but also of the tardive dyskinesea
      was impressive.

PMID- 12224043
TI  - [Olanzapine-induced diabetes mellitus].
AB  - A potential side-effect in the treatment with olanzapine is hyperglycemia or new
      onset diabetes mellitus. There are possible mechanisms by which olanzapine could
      interfere with glucose metabolism but decreased insulin sensitivity due to weight
      gain is of most relevance.

PMID- 12224046
TI  - Role of nephrin in renal disease including diabetic nephropathy.
AB  - Nephrin, a newly described protein, has been localized to the slit membrane
      between adjacent podocytes of the glomerulus. Its discovery followed the
      demonstration of the gene NPHS1 and its mutation, resulting in the absence of the
      protein product, nephrin, in the congenital nephrotic syndrome of the Finnish
      type. The link between permutations in nephrin expression and proteinuria has
      been shown in animal models by using neutralizing antibodies or studying mice
      with inactivation of the nephrin gene. Moreover, the expression of nephrin has
      been shown to be reduced in various animal models of proteinuric renal disease.
      The relationship between changes in nephrin expression and proteinuric renal
      disease in humans is not fully elucidated, with a reduction in expression of this
      protein reported in a range of renal diseases. Diabetic nephropathy, one of the
      major causes of end-stage renal disease, is associated with substantial
      proteinuria and in experimental models with a reduction in slit pore density. In
      experimental models of diabetes, nephrin expression has been described as being
      transiently increased in the first 8 weeks of diabetes, followed in longer-term
      studies with reduced nephrin expression in association with increasing
      proteinuria. An angiotensin II-receptor blocker has been shown to prevent
      depletion in glomerular nephrin expression in the diabetic kidney. Human studies
      in both type 1 and type 2 diabetes suggest down-regulation of nephrin expression
      in the diabetic kidney and it has been postulated that these changes may play a
      role in the pathogenesis of diabetic nephropathy, specifically the development of
      proteinuria in this condition. Although there are other proteins involved in the
      structure of the epithelial podocyte and specifically the slit pore, nephrin
      seems to play a pivotal role in preventing passage of protein through the
      glomerular barrier. Furthermore, it is suggested that the antiproteinuric effects
      of inhibition of the renin-angiotensin system may partly relate to the effects of
      these agents on nephrin expression.

PMID- 12224044
TI  - Determining the one, two, three, or four long and short loci of human complement
      C4 in a major histocompatibility complex haplotype encoding C4A or C4B proteins.
AB  - The complex genetics of human complement C4 with unusually frequent variations in
      the size and number of C4A and C4B, as well as their neighboring genes, in the
      major histocompatibility complex has been a hurdle for accurate epidemiological
      studies of diseases associated with C4. A comprehensive series of novel or
      improved techniques has been developed to determine the total gene number of C4
      and the relative dosages of C4A and C4B in a diploid genome. These techniques
      include (1) definitive genomic restriction-fragment-length polymorphisms (RFLPs)
      based on the discrete duplication patterns of the RCCX (RP-C4-CYP21-TNX) modules
      and on the specific nucleotide changes for C4A and C4B isotypes; (2) module
      specific PCR to give information on the total number of C4 genes by comparing the
      relative quantities of RP1- or TNXB-specific fragments with TNXA-RP2 fragments;
      (3) labeled-primer single-cycle DNA polymerization procedure of amplified C4d
      genomic DNA for diagnostic RFLP analysis of C4A and C4B; and (4) a highly
      reproducible long-range-mapping method that employs PmeI-digested genomic DNA for
      pulsed-field gel electrophoresis, to yield precise information on the number of
      long and short C4 genes in a haplotype. Applications of these vigorously tested
      techniques may clarify the roles that human C4A and C4B gene-dosage variations
      play in infectious and autoimmune diseases.

PMID- 12224047
TI  - The renin-angiotensin-aldosterone system and fibrinolysis in progressive renal
      disease.
AB  - Renal glomerular and interstitial fibrosis is widely viewed as the final common
      pathway to renal failure, regardless of the initiating injury. Similarly, the
      renin-angiotensin-aldosterone system (RAAS) plays an important role in the
      progression of renal disease. This review explores the hypothesis that the RAAS
      causes injury and fibrosis, in part, through effects on plasminogen activator
      inhibitor-1 (PAI-1), the major physiologic inhibitor of plasminogen activators in
      vivo. PAI-1, by inhibiting the production of plasmin from plasminogen, tips the
      balance in favor of extracellular matrix accumulation and promotes fibrosis.
      Interruption of the RAAS decreases both PAI-1 expression and fibrosis in animal
      models. These findings have implications for the clinical management of renal
      disease.

PMID- 12224048
TI  - Contribution of prostaglandin D2 synthase to progression of renal failure and
      dialysis dementia.
AB  - This article reviews the possible role of prostaglandin D(2) synthase (PGD(2)S)
      in the progression of chronic renal failure and dialysis dementia. Such a
      proposal is based on our observation that PGD(2)S significantly increases the
      rate of apoptosis in cultured pig kidney proximal tubule LLC-PK1 and rat neuronal
      PC12 cells. Apoptosis was caspase mediated and inhibitable by PGE(1), PGE(2),
      PGF(2alpha), platelet-derived growth factor (PDGF), and by PGD(2)S inhibitors,
      selenium and anti-PGD(2)S antibody. Apoptosis was restored by the addition of
      downstream metabolic products, PGD(2) and 15 deoxy PG triangle up (12,14)J(2).
      The proposal that PGD(2)S contributes to progression of renal failure and
      dialysis dementia is based on: (1) the progressive creatinine-like increase in
      PGD(2)S levels in blood as renal function decreases, increased renal
      cyclooxygenase (COX) 2 in chronic renal failure, and reported increase in
      apoptosis noted in the remnant kidney model, and (2) a 35- to 150-fold increase
      in blood levels of PGD(2)S in dialysis patients. Both conditions appear to favor
      shifting the PG metabolic pathway to downstream apoptotic metabolites, PGD(2) and
      15 deoxy PG triangle up (12,14)J(2). The diverse role that PGs, growth factors,
      and COX play in progression of chronic renal failure, their interactions with
      PGD(2)S, and the status of COX inhibitors in retarding the progression of renal
      failure are reviewed. In addition, the need for a more systematic longitudinal
      assessment of dementia in dialysis patients by standardized neuropsychologic
      testing, testing blood levels and glycosylated isoforms of PGD(2)S, and the
      effect of COX inhibition and erythropoietin administration on dialysis dementia
      are discussed.

PMID- 12224049
TI  - LPA as a determinant of mesangial growth and apoptosis.
AB  - Mesangial cell proliferation is a prominent feature of progression in many forms
      of renal diseases, including immunoglobulin A nephropathy, lupus nephritis,
      hemolytic uremic syndrome, and diabetic nephropathy. Platelet-derived growth
      factor (PDGF) has received much attention as the major mediator of mesangial cell
      proliferation by autocrine/paracrine mechanisms involving up-regulation of
      mesangial PDGF and its receptor on mesangial cells. In this review, we wish to
      spotlight lysophosphatidic acid (LPA), which in combination with PDGF,
      undoubtedly plays a key role as an autocrine and paracrine mediator in regulating
      mesangial cell growth. We not only showed that PDGF acts as a bimodal molecule
      for mesangial cells, inducing mesangial cell proliferation and death
      simultaneously, but also showed that LPA is a survival factor suppressing PDGF
      induced mesangial cell death, thereby remarkably enhancing mesangial mitogenic
      response by PDGF. We believe that a better understanding of the mechanisms of
      mesangial cell proliferation by the combined action of PDGF and LPA could lead to
      novel diagnostic as well as therapeutic strategies, and thus help to better
      control proliferative glomerulonephritis.

PMID- 12224050
TI  - Brain natriuretic peptide: role in cardiovascular and volume homeostasis.
AB  - The identification of natriuretic peptides as key regulators of natriuresis and
      vasodilatation, and the appreciation that their secretion is under the control of
      cardiac hemodynamic and neurohumoral factors, has caused wide interest. The
      natriuretic peptides are structurally similar, but genetically distinct peptides
      that have diverse actions on cardiovascular, renal, and endocrine homeostasis.
      Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are of
      myocardial cell origin, while cardiac natriuretic peptide (CNP) is of endothelial
      origin. ANP and BNP bind to the natriuretic peptide receptor (NPR-A) which, via
      3' 5'-cyclic guanosine monophosphate (cGMP), mediates natriuresis, vasodialation,
      renin inhibition, and antimitogenic properties. CNP lacks natriuretic action but
      possesses vasodilating and growth inhibiting effects via the guanyl cyclase
      linked natriuretic peptide-B (NPR-B) receptor. All three peptides are cleared by
      natriuretic peptide-C receptor (NPR-C) and degraded by neutral endopeptidase,
      both of which are widely expressed in kidney, lung, and vascular wall. Recently,
      a fourth member of the natriuretic peptide, dendroaspsis natriuretic peptide
      (DNP) has been reported to be present in human plasma and atrial myocardium.

PMID- 12224052
TI  - Calcite microcrystals in the pineal gland of the human brain: first physical and
      chemical studies.
AB  - A new form of biomineralization has been studied in the pineal gland of the human
      brain. It consists of small crystals that are less than 20 microm in length and
      that are completely distinct from the often observed mulberry-type hydroxyapatite
      concretions. A special procedure was developed for isolation of the crystals from
      the organic matter in the pineal gland. Cubic, hexagonal, and cylindrical
      morphologies have been identified using scanning electron microscopy. The crystal
      edges were sharp whereas their surfaces were very rough. Energy dispersive
      spectroscopy showed that the crystals contained only the elements calcium,
      carbon, and oxygen. Selected area electron diffraction and near infrared Raman
      spectroscopy established that the crystals were calcite. With the exception of
      the otoconia structure of the inner ear, this is the only known nonpathological
      occurrence of calcite in the human body. The calcite microcrystals are probably
      responsible for the previously observed second harmonic generation in pineal
      tissue sections. The complex texture structure of the microcrystals may lead to
      crystallographic symmetry breaking and possible piezoelectricity, as is the case
      with otoconia. It is believed that the presence of two different crystalline
      compounds in the pineal gland is biologically significant, suggesting two
      entirely different mechanisms of formation and biological functions. Studies
      directed toward the elucidation of the formation and functions, and possible
      nonthermal interaction with external electromagnetic fields are currently in
      progress.

PMID- 12224053
TI  - Electrical stimulation as an adjunct to spinal fusion: a meta-analysis of
      controlled clinical trials.
AB  - This study was a meta-analysis to examine whether electrical stimulation has a
      specific effect on spinal fusion. Little evidence exists on the efficacy of
      electrical stimulation for improving fusion rate of spinal fusion surgery. Using
      MEDLINE (1966-2000) and EMBASE (1985-1999), a search for articles was carried out
      using the Medical Subject Headings: (1) electric stimulation or electromagnetic
      fields, (2) spinal fusion, (3) controlled or clinical trial, and (4) human. Data
      were extracted from all the hit articles and additionally collected from
      appropriate journal lists. A total of five randomized controlled trials (RCT) on
      bones assessing healing of spinal fusion were identified and scored on
      methodological quality. All the identified studies reported positive findings,
      but the quality score of each trial showed wide flaws. Because of relatively
      homogenous subjects who had spine fusion and radiographic assessment from these
      studies, pooling of the data was able to be performed. Excluding one trial with
      the lowest score, the combined results of four trials, whose major endpoints were
      the success rate of the fusion, revealed a statistically significant effect of
      electrical stimulation with various techniques, but the selected trials still
      showed wide variation in view of stimulation modalities and treatment protocol.
      The pooled result of the studies in this review revealed the efficacy of
      electrical stimulation based on proved methodological quality. As problems on
      therapeutic modality and protocol remain, there is a further need for improvement
      in design to constitute acceptable proof and to establish treatment programs that
      better demonstrate electrical stimulation effects on spinal fusion.

PMID- 12224054
TI  - Effects of a time varying strong magnetic field on release of cytosolic free Ca2+
      from intracellular stores in cultured bovine adrenal chromaffin cells.
AB  - This study was made to explain the mechanisms for the effects of exposure to a
      time varying 1.51 T magnetic field on the intracellular Ca(2+) signaling pathway.
      The exposure inhibited an increase in intracellular Ca(2+) concentration
      ([Ca(2+)](i)) in bovine chromaffin cells induced by addition of bradykinin (BK)
      to a Ca(2+) free medium. The exposure did not change BK induced production of
      inositol 1,4,5-trisphosphate (IP(3)). [Ca(2+)](i) was markedly increased in IP(3)
      loaded cells, and this increase was inhibited by the magnetic field exposure. A
      similar increase in [Ca(2+)](i) by other drugs, which stimulated Ca(2+) release
      from intracellular Ca(2+) stores, was again inhibited by the same exposure.
      However, transmembrane Ca(2+) fluxes caused in the presence of thapsigargin were
      not inhibited by the magnetic field exposure in a Ca(2+) containing medium.
      Inhibition of the BK induced increase in [Ca(2+)](i) by the exposure for 30 min
      was mostly recovered 1 h after exposure ended. Our results reveal that the
      magnetic field exposure inhibits Ca(2+) release from intracellular Ca(2+) stores,
      but that BK bindings to BK receptors of the cell membrane and intracellular
      inositol IP(3) production are not influenced.

PMID- 12224055
TI  - Electrical impedance tomography via filtered-back projection of fan current
      distribution: a numerical simulation.
AB  - An approach to electrical impedance tomography (EIT) data acquisition inspired by
      NMR-filtered back-projection imaging with fan isochromat distribution is
      proposed. A current projection is generated by injecting current at a certain
      point of the sample and simultaneously collecting the current itself at different
      points on the half space opposite the point of current injection. After that, the
      injection is shifted to another point and collected as above and so on. A very
      simple algebra and software support the numerical simulations. This method is
      expected to be more sensitive than the traditional method based on potential
      measurements. A preliminary low resolution experiment is presented.

PMID- 12224056
TI  - On the "unreasonable" effects of ELF magnetic fields upon a system of ions.
AB  - A recent experiment on a physical, nonbiological system of ions at room
      temperature has proved that microscopic ion currents can be induced by applying
      simultaneously two parallel magnetic fields, one rather weak static field, (-
      >)B(0) and one much weaker alternating field, (-->) B(ac),[B(ac) approximately
      10(-3) B(0)] whose frequency coincides with the cyclotron frequency v =
      qB(0)/2pim of the selected ion. As a result, ionic bursts lasting up to 20 s and
      with amplitude up to 10 nA arise. The much larger exchanges of energy induced by
      thermal agitation (the "kT-problem") appear to play no role whatsoever. We have
      analyzed this problem in the framework of coherent quantum electrodynamics,
      reaching the following conclusions: (a) as has been shown in previous articles,
      water molecules in the liquid and solute ions are involved in their ground state
      in coherent ordered configurations; (b) ions are able to move without collisions
      among themselves in the interstices between water coherence domains; (c) because
      of coherence, ions can follow classical orbits in the magnetic fields. A full
      quantitative understanding of the experiments is thus reached.

PMID- 12224057
TI  - Verapamil protective effect on natural and artificial magnetic field
      cardiovascular impact.
AB  - Previously we found an opposite effect of artificial static magnetic field (SMF)
      and natural geomagnetic field (GMF) on arterial baroreceptors. A 0.35 T SMF
      increased baroreflex sensitivity (BRS), whereas GMF disturbance decreased BRS.
      Here, we investigated interrelated impacts on arterial baroreceptors of 0.35 T
      SMF, generated by Nd(2)-Fe(14)-B alloy magnets, GMF, and verapamil, a Ca(2+)
      channel blocking agent. We measured BRS in rabbits before and after local SMF
      exposure of sinocarotid baroreceptors or after simultaneous SMF and verapamil
      application, in conjunction with geomagnetic disturbance during actual
      experimental run (determined by K-index) and geomagnetic disturbance over the
      preceding 24 h of each experiment (A(k)-index). BRS was estimated from peak
      responses of mean arterial pressure (MAP) and heart rate, expressed as
      percentages of the resting values preceding each pair of pressure (phenylephrine)
      and depressor drug (nitroprusside) injections. Prior to verapamil and/or SMF
      application we found a significant positive correlation of K-index with MAP (t =
      2.39, P =.021, n = 44), but negative with BRS (t = -4.60, P =.0003, n = 44), and
      found a negative correlation of A(k)-index with BRS (t = -2.7, P = 0.01, n = 44).
      SMF induced an increase in BRS (0.79 +/- 0.1 vs. 1.15 +/- 0.1 bpm%/mmHg%, initial
      value vs. SMF exposure, P <.0002, n = 26). Verapamil infusion blocked the SMF and
      GMF effect on BRS, indicating Ca(2+) channels as a possible site of both fields'
      impact. SMF and GMF probably affect baroreceptor sensory transduction, modulating
      baroreceptor membranes' Ca(2+) channel permeability.

PMID- 12224058
TI  - Non-perceptible body current ELF effects as defined by electric shock safety
      data.
AB  - Non-perceptible body currents that arise from contacting exposed conductors that
      are part of household appliances, are considered in the light of past electric
      shock safety studies. When these appliances are touched, the older, nongrounded
      appliances exhibited orders of magnitude greater in-tissue electric fields than
      the newer grounded appliances or other grounded, exposed, household conductors,
      such as water faucets.

PMID- 12224059
TI  - Rats can discriminate illuminance, but not magnetic fields, as a stimulus for
      learning a two-choice discrimination.
AB  - In each of the two experiments, nine rats were trained for 64 trials (eight
      trials per day) to determine if they could acquire a two-choice discrimination
      based on a specified discriminative stimulus (S(D)). In one experiment, the S(D)
      was a change in ambient illumination, while in the second experiment the S(D) was
      a change in the combination of sinusoidal 60 Hz and static magnetic field (MF)
      and any cues attendant to energizing the coils that produced the MF exposure. The
      rats that had a change in illuminance as the S(D) learned the two-choice task
      easily, P <.001, whereas the rats having a change in MFs as the S(D) did not.

PMID- 12224060
TI  - Comment: Influence of stationary magnetic fields on water relations in lettuce
      seeds.

PMID- 12224062
TI  - Comment: "Project NEMESIS: Perception of a 50 Hz electric and magnetic field at
      low intensities".

PMID- 12224064
TI  - Association between fetal nuchal translucency thickness in first trimester and
      subsequent gestational hypertension and preeclampsia.
AB  - Increased fetal nuchal translucency (NT) in the first trimester is associated
      with adverse pregnancy outcomes. Whether the increased NT is also associated with
      an increased frequency of pregnancy-associated hypertension (PAH) is not known.
      Seven hundred and seventy-nine pregnant women who received NT-based Down syndrome
      screening and delivered their babies at our hospital by September 2000 were
      enrolled into this study. Among these women, there are 46 cases of preeclampsia,
      68 cases of gestational hypertension (GH); 665 women without any adverse
      pregnancy outcomes served as controls. Correlation analysis demonstrated that NT
      MoM (multiples of median) level had a positive association with maternal
      diastolic blood pressure at the time of admission for delivery (r = 0.104; p <
      0.01). The severity of PAH was concordant with the stepwise increase of mean NT
      MoM level, which was 0.88 in control, 1.07 in gestational hypertension, and 1.13
      in preeclampsia (p < 0.001). Using the 95th (1.52 MoM) and 90th (1.31 MoM)
      percentiles of NT thickness as cut-offs, the sensitivities and odds ratios of the
      women at risk for developing GH after 20 weeks of gestation were 8.8%, 19.1% and
      1.98, 2.15 respectively, while for preeclampsia were 10.9%, 28.3% and 2.49, 3.58
      respectively. It is concluded that the pathological changes in the placenta
      responsible for the development of PAH may also influence the physiological
      decrease of NT thickness in late first trimester. However, the sensitivity of
      fetal NT measurement in first trimester is not sufficient as a single marker for
      predicting the pregnant women at risk for subsequent PAH.

PMID- 12224065
TI  - CGH in the detection of confined placental mosaicism (CPM) in placentas of
      abnormal pregnancies.
AB  - Comparative genomic hybridization (CGH) was applied to samples taken from various
      sites of placentas originating from complicated pregnancies: 24 with intrauterine
      growth restriction (IUGR), one with multiple fetal malformation, one with
      toxemia, one with hydrocephalus and two with undetectable maternal serum alpha
      fetoprotein (MSAFP). One of the most common aberrations in the IUGR cases was the
      addition of a whole or part of the X chromosome. Other aberrations such as
      additional Y chromosome or of 13(q22) or loss of chromosome 17 also appeared in
      different cases. In one IUGR case trisomy 8 (in one site) and 47,XXY (in all
      sites) were detected. In the two cases with undetectable MSAFP monosomy 16 was
      found. Some of the results were also confirmed by the FISH technique. In all the
      control cases (six normal and five with aneuploidy) CGH concurred with the known
      karyotype. Our results demonstrate the usefulness of the CGH technique in the
      genetic evaluation of fresh and paraffin embedded placentas in problematic
      pregnancies even when morphology is normal. However, it is very important to take
      multiple samples from different sites of the placenta.

PMID- 12224066
TI  - Nuchal translucency measurements in consecutive normal pregnancies. Is there a
      predisposition to increased levels?
AB  - OBJECTIVE: The current study aims to assess the relative risk of isolated
      increased nuchal translucency (NT) in consecutive normal pregnancies. METHODS: A
      retrospective search of the fetal medicine unit database in which NT assessment
      was conducted. Only singleton fetuses with an unremarkable pregnancy outcome were
      included in this study. The repeated NT either at a threshold of >2.5 mm or > or
      =95th centile of the normal range for various CRLs (2 mm at a CRL < or =44 mm to
      2.85 mm at CRLs 83-84 mm) was assessed. Pearson's correlation was applied to
      investigate any correlation between a log(10) NT obtained in two consecutive
      pregnancies. The chance of an increased NT in the first pregnancy followed by
      similar results in the subsequent one was assessed using Fisher's exact test.
      RESULTS: Ninety-two pregnant women with two consecutive normal pregnancies were
      identified. There was a highly significant correlation between the log(10) NT
      values measured in the consecutive pregnancies (r = 0.38; p < 0.001). The
      relative risk of an isolated NT > or =2.5 mm in the first pregnancy to be
      followed by a similar finding in the subsequent one was 18.21 (95% confidence
      interval [CI]: 3.62-91.55). The relative risk of an isolated NT > or =95th
      centile in the first pregnancy to be followed by a similar result in the
      subsequent one was 21 (95% CI: 4.53-97.44). CONCLUSION: The current results
      indicate a significant correlation of NT values in consecutive unaffected
      pregnancies. There also was a predisposition for a repeated isolated increased NT
      in subsequent pregnancies. Additional series and more information are needed
      before firm conclusions can be made.

PMID- 12224067
TI  - Prenatal diagnosis and carrier detection for Athabascan severe combined
      immunodeficiency disease.
AB  - OBJECTIVES: Severe combined immunodeficiency disease occurs at a high incidence
      among Athabascan-speaking Navajo and Apache children (SCIDA). We linked the SCIDA
      gene to chromosome 10p and recently identified a common nonsense mutation in
      Artemis/SCIDA. In this study we compared polymorphic markers linked to SCIDA and
      the point mutation which creates an NspI site on exon 8 for prenatal diagnosis
      and carrier detection. METHODS: We tested five amniocentesis samples, two cord
      blood and two blood samples from eight at-risk families using polymorphic DNA
      markers tightly linked to SCIDA. We amplified the region of exon 8 of
      Artemis/SCIDA and evaluated the products for the NspI site in each sample plus
      samples from 30 unrelated healthy Navajos. RESULTS: We correctly predicted that
      three were affected and six were unaffected. Two of the unaffected appear to be
      carriers based on our haplotype analysis. Retrospective analysis for the gene
      mutation confirmed the DNA analysis. Finally, 10% of the normal Navajo controls
      were carriers. CONCLUSIONS: We demonstrate the feasibility of prenatal diagnosis
      and carrier detection for SCIDA in the families at risk as well as the
      availability of a rapid screening test for the SCIDA founder mutation that can be
      used in all Navajo and Apache newborns and at-risk fetuses.

PMID- 12224068
TI  - Factors affecting the decision regarding amniocentesis in women at genetic risk
      because of age 35 years or older.
AB  - OBJECTIVE: To evaluate the effects of anamnestic factors and sonographic findings
      on the patient's decision regarding amniocentesis in a cohort of women at genetic
      risk because of advanced age. METHODS: All women 35 years of age or older
      registered for prenatal care between January 1990 and December 1998 were asked
      about their attitude towards genetic amniocentesis during the course of
      individual genetic counseling and once again after ultrasound examination
      inclusive of markers of aneuploidies (nuchal fold thickness greater than 6 mm,
      renal pyelectasis, choroid plexus cysts, and hyperechogenic bowel). Their
      attitudes towards genetic amniocentesis before and after ultrasound examination
      were compared using chi-square, Fisher's exact test, Mann-Whitney U-test, and
      logistic regression analysis, with a two-tailed p < 0.05 or an odds ratio (OR)
      with 95% confidence interval (CI) not inclusive of the unity considered
      significant. RESULTS: Among the 1486 women in the cohort, 1368 (97%) expressed an
      opinion towards genetic testing at the time of counseling: 501 (37%) were in
      favor and 867 (63%) were against having the procedure. After ultrasonographic
      examination, 33% (446/1368) of women opted for amniocentesis, 36% (146/402) after
      abnormal findings and 31% (300/966) after normal ultrasound findings.
      Significantly more women with abnormal than normal ultrasound findings opted for
      diagnostic testing in both groups. Overall, only 8% (115/1368) of women changed
      their attitude towards diagnostic testing after ultrasonographic examination.
      Normal sonographic findings were three times more likely to change the attitude
      of women initially interested in amniocentesis than abnormal sonographic findings
      did in women a priori not interested in the procedure (20% versus 7%, p < 0.001,
      OR = 3.2, 95% CI 1.8; 5.8). CONCLUSIONS: In a cohort of women at genetic risk
      because of advanced age, the key determinant of the choice regarding genetic
      amniocentesis is the a priori opinion of the woman towards the procedure, which
      was expressed by 93% of women. Ultrasonography plays a secondary role in changing
      or confirming women's attitude towards invasive diagnostic testing. Normal
      sonographic findings affect women's decisions more powerfully than abnormal
      sonographic findings, suggesting that ultrasonography has an important reassuring
      function for the woman.

PMID- 12224069
TI  - Optimising the timing for nuchal translucency measurement.
AB  - It appears from current evidence that the most effective screening strategy for
      Down syndrome will involve a combination of first trimester nuchal translucency
      and serum biochemistry, whether performed in the first or second trimester. The
      aim of this study was to determine the optimum gestation based upon menstrual
      dates at which to schedule nuchal translucency (NT) measurement for the
      evaluation of fetal Down syndrome risk. Five thousand eight hundred and thirty
      five pregnancies had an ultrasound scan scheduled between 11 and 14 completed
      weeks of gestation based upon either the last menstrual period (n = 3199) or a
      prior ultrasound scan (n = 2636). For last menstrual period-based ultrasound
      scans, with advancing gestation the frequency of missed miscarriage significantly
      decreased (p = 0.009, chi squared test), as did the need to reschedule a further
      scan because the gestation of the scheduled scan was too early to measure NT (p <
      0.0001, Chi-squared test). In contrast, with advancing gestation the rate of
      unsuccessful NT measurement because the crown-rump length (CRL) was greater than
      84 mm significantly increased (p < 0.0001, Chi-squared test). Of the women who
      had had an earlier ultrasound, 42 (1.6%) had a missed miscarriage and 9 (0.3%)
      were over gestation at the time of the NT scan. These data suggest that when only
      the last menstrual period is known the optimum time to schedule a nuchal
      translucency measurement is at 12 to 13 weeks' gestation.

PMID- 12224070
TI  - Decreased first trimester PAPP-A is a predictor of adverse pregnancy outcome.
AB  - OBJECTIVE: Low levels of maternal serum pregnancy associated plasma protein-A
      (PAPP-A) have been linked to chromosome anomalies such as trisomy 21, 13 and 18,
      triploidy and sex chromosome aneuploidy. Low levels of PAPP-A have also been
      implicated in spontaneous miscarriage. The purpose of this study was to evaluate
      whether low levels of first trimester PAPP-A are predictive of other adverse
      pregnancy outcomes. STUDY DESIGN: The study included patients with singleton
      pregnancies who underwent combined first trimester screening using nuchal
      translucency (NT) and maternal serum free beta-human chorionic gonadotrophin
      (free beta-hCG) and PAPP-A at 10-13 weeks' gestation. Patients with chromosome
      aberrations or fetal anomalies were excluded. Serum marker levels were expressed
      as gestational age-specific multiples of the median (MoMs). The incidences of
      various adverse pregnancy outcomes (spontaneous preterm labor, fetal growth
      restriction (FGR), proteinuric and non-proteinuric pregnancy induced hypertension
      (PIH), intrauterine fetal demise, oligohydramnios, spontaneous miscarriage and
      placental abruption) were evaluated, according to maternal PAPP-A MoM levels.
      RESULTS: Of the 1622 patients in the study, pregnancy complications were observed
      in 184 (11.3%). Patients with PAPP-A < or =0.25 MoM had significantly higher
      rates of FGR (RR = 3.12), proteinuric PIH (RR = 6.09), spontaneous miscarriage
      (RR = 8.76). No statistically significant differences were noted for other
      adverse outcomes evaluated Women with PAPP-A < or =0.50 MoM also had
      significantly higher rates of FGR (RR = 3.30) and spontaneous miscarriage (RR =
      3.78). CONCLUSIONS: We conclude that decreased levels of first trimester maternal
      serum PAPP-A are predictive not only of chromosome anomalies but also of adverse
      pregnancy outcome.

PMID- 12224071
TI  - Clostridium welchii infection following amniocentesis: a case report and review
      of the literature.
AB  - We report a case of severe Clostridium welchii infection following amniocentesis
      with septicaemia, haemolysis, DIC, pulmonary oedema and renal failure. Full
      recovery occurred following aggressive conservative management using antibiotics,
      endometrial curettage and intensive monitoring. The patient retained her uterus
      and had a successful pregnancy two years later although caesarean section for
      uterine rupture was required. Conservative management with conservation of the
      uterus and ovaries may be a safe and effective option in the management of severe
      Clostridium infections, using antibiotics, endometrial curettage and
      multidisciplinary team input.

PMID- 12224072
TI  - Reference ranges for Doppler-assessed pulmonary venous blood flow velocities and
      pulsatility indices in normal human fetuses.
AB  - OBJECTIVES: To establish reference ranges with gestation for Doppler parameters
      of fetal pulmonary venous blood flow during the second half of pregnancy,
      including not only peak velocities, but also relative indices reflecting left
      atrial pressure changes. METHODS: In this cross-sectional study, 114 normal
      singleton pregnancies between 19 and 37 weeks' gestation were examined by Doppler
      echocardiography. In 98 fetuses, peak systolic velocity (S), peak diastolic
      velocity (D), end-diastolic velocity (A), and time velocity integral (TVI) were
      measured, and S/D ratio, pulsatility index for veins (PIV), as well as peak
      velocity index for veins (PVIV), were calculated. Regression analysis was used to
      determine reference ranges with gestation. RESULTS: With advancing gestation, a
      significant increase in S, D and A velocities as well as in TVI, was observed.
      Whereas the S/D ratio remained constant, PVIV and PIV decreased significantly
      during the second half of pregnancy. CONCLUSIONS: During the second half of
      pregnancy the increase in left atrial and ventricular compliance is reflected by
      the observed decrease in PIV and PVIV, which could be mainly due to the increased
      flow during atrial contraction. Such relative Doppler indices are better
      comparable than absolute values and are independent from the insonation angle.
      Potential clinical applications for such Doppler indices are conditions with
      possibly impaired left atrial function, like heart defects with left atrial
      obstruction or late stages of severe intrauterine growth retardation.

PMID- 12224073
TI  - Choroid plexus cysts in the mid-trimester fetus--practical application suggests
      superiority of an individualized risk method of counseling for trisomy 18.
AB  - OBJECTIVES: Analysis of a referral population of patients with choroid plexus
      cysts (CPCs) was performed to compare an average risk method of counseling to an
      individualized risk method. METHODS: A total of 395 patients referred to a
      Prenatal Diagnosis Center were included, of whom 341 had isolated CPCs and 54 had
      associated ultrasound abnormalities. For isolated CPCs, an average risk of 1/150
      for aneuploidy was compared to an individualized risk assessment [prior risk as
      determined by maternal age or serum screening multiplied by the likelihood ratio
      established by Gupta et al. (1997)]. Accuracy, cost, and procedure-related losses
      were assessed. RESULTS: Both methods resulted in 100% sensitivity. The
      individualized method resulted in greater specificity, decreased costs, and
      (theoretically) fewer procedure-related pregnancy losses. CONCLUSIONS: An
      individualized risk method of counseling utilizing the likelihood ratios
      established by Gupta et al. (1997) was superior to an average risk method for
      assessing trisomy 18 risk in the setting of CPC detected in mid-trimester.

PMID- 12224074
TI  - The significance of the nuchal fold in the second trimester fetus.

PMID- 12224075
TI  - Prenatal and postnatal characterization of Y chromosome structural anomalies by
      molecular cytogenetic analysis.
AB  - We describe three cases in which we used fluorescence in situ hybridization
      (FISH), polymerase chain reaction (PCR) and comparative genomic hybridization
      (CGH) to characterize Y chromosome structural anomalies, unidentifiable by
      conventional G-banding. Case 1 was a 46,X,+mar karyotype; FISH analysis revealed
      an entire marker chromosome highlighted after hybridization with the Y chromosome
      painting probe. The PCR study showed the presence of Y chromosome markers AMG and
      SY620 and the absence of SY143, SY254 and SY147. CGH results confirmed the loss
      of Yq11.2-qter. These results indicated the presence of a deletion:
      del(Y)(q11.2). Case 2 was a 45,X [14]/46,XY[86] karyotype with a very small Y
      chromosome. The PCR study showed the presence of Y chromosome markers SY620 and
      AMG, and the absence of SY143, SY254 and SY147. CGH results showed gain of Yq11.2
      pter and loss of Yq11.2-q12. These results show the presence of a Yp
      isodicentric: idic(Y)(q11.2). Case 3 was a
      45,X,inv(9)(p11q12)[30]/46,X,idic(Y)(p11.3?),inv(9)(p11q12)[70] karyotype. The
      FISH signal covered all the abnormal Y chromosome using a Y chromosome paint. The
      PCR study showed the presence of Y chromosome markers AMG, SY620, SY143, SY254
      and SY147. CGH only showed gain of Yq11.2-qter. These results support the
      presence of an unbalanced (Y;Y) translocation. Our results show that the combined
      use of molecular and classical cytogenetic methods in clinical diagnosis may
      allow a better delineation of the chromosome regions implicated in specific
      clinical disorders.

PMID- 12224076
TI  - Fetal fibrochondrogenesis at 26 weeks' gestation.
AB  - Fibrochondrogenesis is a rare and lethal osteochondrodysplasia with an autosomal
      recessive mode of inheritance. We report a male fetus in which the diagnosis of
      lethal osteochondrodysplasia was suspected on prenatal ultrasound and
      radiological examinations during the second trimester of pregnancy. After
      termination of pregnancy, fibrochondrogenesis was diagnosed by radiological
      examination and histological study of fetal bones. Interwoven fibrous septa and
      fibroblastic degeneration of chondrocytes are pathognomonic. The recurrence rate
      is 25% and accurate diagnosis is necessary to enable genetic counselling.

PMID- 12224077
TI  - Ethical decision-making in prenatal diagnosis and termination of pregnancy: a
      qualitative survey among physicians and midwives.
AB  - OBJECTIVES: This study was aimed at exploring the conflicts and ethical problems
      experienced by professionals involved in prenatal diagnosis and termination of
      pregnancy (TOP) in order to improve the understanding of decision-making
      processes and medical practices in the field of prenatal diagnosis. METHODS:
      Qualitative study with in-depth tape-recorded interviews conducted in three
      tertiary care maternity units in France, between May 1999 and March 2000. All
      full-time obstetricians and half of the full-time midwives were contacted.
      Seventeen obstetricians and 30 midwives participated (three refusals, five
      missing). Interviews were transcribed and analysed successively by two different
      researchers. RESULTS: All respondents stated that prenatal diagnosis and TOP
      raised important ethical dilemmas, the most frequent being request for abortion
      in case of minor anomalies. They pointed out the inability of our society to
      appropriately care for disabled children and the risk of eugenic pressures. The
      decisions and practices in prenatal diagnosis should be debated throughout
      society. All respondents reported that their unit did not have protocols for
      deciding when a TOP was justifiable. The transmission of information to the women
      appeared to be a problematic area. Moral conflicts and emotional distress were
      frequently expressed, especially by midwives who mentioned the need for more
      discussions and support groups in their department. CONCLUSION: Health
      professionals involved in prenatal diagnosis face complex ethical dilemmas which
      raise important personal conflicts. A need for more resources for counselling
      women and for open debate about the consequences of the current practices clearly
      emerged.

PMID- 12224078
TI  - Spine length measurement in the first trimester of pregnancy.
AB  - OBJECTIVES: The aim of the study was to evaluate spine length as an indicator of
      skeletal growth in the first trimester of pregnancy and to provide a nomogram of
      spine length at the end of the first trimester of pregnancy. METHODS: The study
      was carried out on 420 single pregnancies, at gestational ages ranging from 11 to
      14 weeks, using high-resolution transabdominal echography. Biparietal diameter
      and crown-rump length (CRL) were measured to date the pregnancy. Using the same
      scanning plane used to measure CRL, the whole spine length in antero-dorsal
      position can be visualized as a double hyperechoic line from 10 weeks of
      gestation onwards. Spine length was measured three times by one observer and the
      mean of the three measurements was considered as definitive. Forty fetuses had
      multiple measurements for interobserver and intraobserver error analysis.
      RESULTS: Linear relationship between spine length, and gestational age,
      biparietal diameter and CRL were demonstrated. Spine length (millimetres) as a
      function of gestational age (days) was expressed by the regression equation:
      spine length = 1.09 x (gestational age in days) -60.56, with a determination
      coefficient of R(2) = 0.744. Spine length ranged from 21.5 mm at 11 weeks to 41.9
      mm at 14 weeks. CONCLUSION: The data obtained showed that spine length increased
      progressively from the end of the first trimester to the beginning of the second.
      A high correlation between spine length, gestational age, biparietal diameter,
      and CRL was observed. Spine length measurement could therefore be considered a
      good indicator of fetal growth.

PMID- 12224080
TI  - Molecular prenatal diagnosis of Smith-Lemli-Opitz syndrome is reliable and
      efficient.
AB  - Smith-Lemli-Opitz (RSH) syndrome (SLOS, OMIM 270400) is a relatively common,
      autosomal recessive disorder of cholesterol biosynthesis with a broad spectrum of
      phenotypic abnormalities caused by mutations of the 7-dehydrocholesterol
      reductase gene (DHCR7) on chromosome 11. Prenatal diagnosis can be established by
      detection of elevated 7-dehydrocholesterol or of SLOS-causing mutations in the
      DHCR7 gene. We report here our experience with molecular prenatal diagnosis of
      SLOS. Mutation analysis of the DHCR7 gene was performed in chorionic villus
      samples of 13 pregnancies of couples with a family history of SLOS and known SLOS
      genotypes. This approach is accurate and reliable. If facilities for biochemical
      analysis are not available, or in cases with ambiguous biochemical patterns,
      molecular prenatal diagnosis is an attractive, alternative option.

PMID- 12224079
TI  - Prenatal diagnosis of Milroy's primary congenital lymphedema.
AB  - Milroy's primary congenital lymphedema (PCL) (hereditary lymphedema type I,
      Milroy disease) is present at birth, and mostly affects the dorsal aspects of
      feet. It is mostly a life-long condition but does not affect longevity.
      Complications are rare except for chronic discomfort and warmness of affected
      areas. PCL is an autosomal dominant disease with incomplete penetrance due to a
      mutation in the gene locus encoding for VEGFR3 with resultant dysgenesis of
      microlymphatic vessels. We report on two fetuses where ultrasonographic
      examination at 15 weeks of gestation showed significant edema of the dorsal
      aspects of both feet with no evidence of other major malformations. Whereas in
      one fetus the edema resolved completely, it persisted in the second fetus and
      proved after birth to be of lymphedematous nature. To the best of our knowledge,
      this is the first report of early prenatal diagnosis of primary congenital
      lymphedema via fetal ultrasonographic examination and of spontaneous resolution
      of lymphedema during fetal life.

PMID- 12224081
TI  - Distinct prenatal ultrasonographic cranial and cerebral findings in terminal
      deletion of the short arm of chromosome 1.

PMID- 12224082
TI  - Nuchal edema as the first sign of fetal valproate syndrome.

PMID- 12224083
TI  - Down syndrome livebirth rate in the eastern part of Switzerland between 1980 and
      1996 stays constant in spite of growing numbers of prenatally diagnosed and
      subsequently terminated cases.

PMID- 12224084
TI  - Prenatal detection of trisomy 21 on nucleated red blood cells enriched from
      maternal circulation by using fluorescence in situ hybridization.

PMID- 12224085
TI  - Fetal thymus and the 22q11.2 deletion.

PMID- 12224086
TI  - The sixth clinical report of a rare association: agnathia-holoprosencephaly-situs
      inversus.

PMID- 12224088
TI  - Enhancing the antitumoral effect of hypericin-mediated photodynamic therapy by
      hyperthermia.
AB  - BACKGROUND AND OBJECTIVES: In the previous study, we have found a synergistic
      effect on the RIF-1 tumor cell killing when hypericin-mediated photodynamic
      therapy (PDT) was combined with hyperthermia. The purpose of the present study
      was to investigate the antitumoral effect of hypericin-PDT in combination with
      hyperthermia in the RIF-1 mouse tumor model. STUDY DESIGN/MATERIALS AND METHODS:
      Tumor response to PDT in combination with hyperthermia was compared to the
      response to PDT or hyperthermia alone. To explore the possible mechanism involved
      in the interaction of PDT and hyperthermia, we determined the tumor cell survival
      by in vivo/in vitro cell survival assay and analyzed the functional blood vessels
      by Hoechst 33342 staining. The mode of cell death was examined by TUNEL assay.
      RESULTS: Enhanced tumor response was obtained by PDT immediately followed by
      hyperthermia. Tumor cell survival assay revealed that indirect vascular effect
      contributed greatly to the overall tumor cell death induced by PDT with
      hypericin, whereas direct tumor cytotoxicity played a major role in hyperthermia
      induced tumor cell killing. Combining PDT with hyperthermia brought about a
      synergistic interaction on direct tumor cell killing. Even though PDT or
      hyperthermia alone induced severe blood vessel shutdown and the combined
      treatments led to significant potentiation of the vascular damage as examined by
      Hoechst staining, the gain in tumor cell death as a result of this secondary
      vascular effect was limited after the combined treatments. Following the cellular
      damage by PDT in combination with hyperthermia, tumor cells were triggered to
      undergo apoptosis. CONCLUSIONS: Our study demonstrated the possibility of using
      hyperthermia to potentiate the antitumoral effect of hypericin-mediated PDT.

PMID- 12224087
TI  - Detection of squamous cell carcinomas and pre-cancerous lesions in the oral
      cavity by quantification of 5-aminolevulinic acid induced fluorescence endoscopic
      images.
AB  - BACKGROUND AND OBJECTIVES: Studies of 5-aminolevulinic acid-induced
      protoporphyrin IX fluorescence have shown a sensitivity of 95-100% for oral
      cancer diagnosis, but the specificity is only about 50-60%. Here, we explore the
      applicability of quantifying PPIX fluorescence images to improve the diagnostic
      specificity and detect early oral lesions. STUDY DESIGN/MATERIALS AND METHODS:
      PPIX Fluorescence endoscopy and imaging were performed on 28 patients with a
      known or suspected premalignant or malignant oral cavity lesion. A total of 70
      biopsies were taken from the tissue sites imaged for histological analysis. The
      red-to-blue and red-to-green intensity ratios were calculated from the
      fluorescence images to correlate with histology. RESULTS: Suspicious lesions
      display bright reddish fluorescence, while normal mucosas exhibit blue color
      background in the fluorescence images. The red-to-blue and red-to-green intensity
      ratios of malignant tissues are larger than those of benign tissues. Combining
      the two ratio diagnostic algorithms yields a sensitivity and specificity of 95%
      and 97%, respectively, exceeding each diagnostic algorithm alone for
      discriminating malignant tissue from benign tissue. CONCLUSIONS: Quantifying PPIX
      fluorescence endoscopic images combined with the ratio diagnostic algorithms
      developed in this study has the potential to significantly improve the
      noninvasive diagnosis of oral cavity lesions in vivo.

PMID- 12224089
TI  - Effect of Er:YAG laser on bond strength to dentin of a self-etching primer and
      two single-bottle adhesive systems.
AB  - BACKGROUND AND OBJECTIVES: To assess the effect of erbium:yttrium aluminium
      garnet (Er:YAG) laser on bond strength to dentin of a self-etching primer
      (Clearfil Liner Bond 2V, CL2V) and two single-bottle agents (Excite, EX; Gluma
      One Bond, GB). STUDY DESIGN/MATERIALS AND METHODS: Thirty human molars were
      selected, roots were removed and crowns were bisected, providing 60 halves.
      Specimens were included and ground to expose dentin. Bonding site was limited and
      samples were assigned to three groups: I, CL2V; II, EX; III, GB. Dentin was
      either conventionally treated or submitted to laser conditioning + conventional
      treatment. The adhesive protocol was performed, samples were stored for 24 hours
      and bond strength was tested to failure (0.5 mm/min). RESULTS: Statistical
      analysis showed a decrease in bond strength for lased subgroups and this drop was
      more evident for EX. CL2V provided the best overall results, regardless of the
      surface treatment. CONCLUSIONS: Er:YAG laser may adversely affect bond strength
      in higher or lesser degree, depending on the adhesive system used.

PMID- 12224090
TI  - Effects of Er:YAG laser irradiation on human dentin: polarizing microscopic,
      light microscopic and microradiographic observations, and FT-IR analysis.
AB  - BACKGROUND AND OBJECTIVES: The effects of Er:YAG laser irradiation on dentin have
      not been sufficiently investigated. The purpose of this study was to investigate
      the effects of Er:YAG laser irradiation on dentin. STUDY DESIGN/MATERIALS AND
      METHODS: After cavities were prepared using Er:YAG laser irradiation or rotary
      cutting instruments, histological observations of cavity-floor dentin utilizing
      polarizing microscopy, microradiography and light microscopy, and analysis of
      composition of cavity-floor dentin using Fourier-transformed (FT-IR) spectrometry
      were conducted. RESULTS: In the laser-treated side, a deeply stained basophilic
      layer was observed. The number of odontoblastic processes present was obviously
      less in the laser-treated side than in the bur-treated side. FT-IR analysis
      revealed that compared to the bur-treated side, a broad background peak at around
      1,600 cm(-1) was present. CONCLUSIONS: Er:YAG laser irradiation might have
      denatured the organic materials of dentin.

PMID- 12224091
TI  - Ablation rate and micromorphological aspects with Nd:YAG picosecond pulsed laser
      on primary teeth.
AB  - BACKGROUND AND OBJECTIVES: We have investigated the fundamental aspects of Nd:YAG
      laser at the picosecond pulse regime interacting with primary teeth. Because
      little is present in the literature concerning specific laser ablation for
      primary teeth with respect to enamel and dentin, this work may open perspectives
      for new investigations. STUDY DESIGN/MATERIALS AND METHODS: Using a picosecond
      Nd:YAG laser, different power levels (200, 300, and 350 mW) and different
      exposition times (5, 10, and 15 seconds) were considered. RESULTS: Micro
      morphological aspects of the laser-tooth interaction showed collateral effects in
      enamel more accentuated than in dentin. Penetration depth in dentin seems to
      scale up in rate as the time of application progress, for enamel the behavior is
      the opposite. The overall ablated volume is higher in dentin when compared with
      enamel, which results in a higher ablated rate as well. CONCLUSIONS: Specific
      ablation characteristics are observed in either dentin or enamel.

PMID- 12224092
TI  - Mechanism of water augmentation during IR laser ablation of dental enamel.
AB  - BACKGROUND AND OBJECTIVES: The mechanism of water augmentation during IR laser
      ablation of dental hard tissues is controversial and poorly understood. The
      influence of an optically thick applied water layer on the laser ablation of
      enamel was investigated at wavelengths in which water is a primary absorber and
      the magnitude of absorption varies markedly. STUDY DESIGN/MATERIALS AND METHODS:
      Q-switched and free running Er: YSGG (2.79 microm) and Er:YAG (2.94 microm), free
      running Ho:YAG and 9.6 microm TEA CO(2) laser systems were used to produce linear
      incisions in dental enamel with and without water. Synchrotron-radiation IR
      spectromicroscopy with the Advanced Light Source at Lawrence Berkeley National
      Laboratory was used to determine the chemical changes across the laser ablation
      profiles with a spatial resolution of 10-microm. RESULTS: The addition of water
      increased the rate of ablation and produced a more desirable surface morphology
      during enamel ablation with all the erbium systems. Moreover, ablation was
      markedly more efficient for Q-switched (0.15 microsecond) versus free-running
      (150 microsecond) erbium laser pulses with the added water layer. Although the
      addition of a thick water layer reduced the rate of ablation during CO(2) laser
      ablation, the addition of the water removed undesirable deposits of non-apatite
      mineral phases from the crater surface. IR spectromicroscopy indicates that the
      chemical composition of the crater walls deviates markedly from that of
      hydroxyapatite after Er:YAG and CO(2) laser irradiation without added water. New
      mineral phases were resolved that have not been previously observed using
      conventional IR spectroscopy. There was extensive peripheral damage after
      irradiation with the Ho:YAG laser with and without added water without effective
      ablation of enamel. CONCLUSIONS: We postulate that condensed mineral phases from
      the plume are deposited along the crater walls after repetitive laser pulses and
      such non-apatitic phases interfere with subsequent laser pulses during IR laser
      irradiation reducing the rate and efficiency of ablation. The ablative recoil
      associated with the displacement and vaporization of the applied water layer
      removes such loosely adherent phases maintaining efficient ablation during
      multiple pulse irradiation.

PMID- 12224094
TI  - Follow-up survey of 308-nm laser treatment of psoriasis.
AB  - BACKGROUND AND OBJECTIVES: UVB treatment with a 308-nm excimer laser is a new
      treatment modality for localized psoriasis. The purpose of this study is to
      assess patients' impressions and satisfaction with 308-nm laser treatment of mild
      to moderate psoriasis. STUDY DESIGN/MATERIALS AND METHODS: Telephone survey data
      were obtained from patients after participation in a case series study of 124
      patients with mild to moderate psoriasis treated with 308-nm UVB laser treatment
      for a target plaque and other lesions. The survey included information on changes
      in the target plaque, remission time, changes in other areas of psoriasis,
      satisfaction with the result, side effects of treatment, and efficacy relative to
      other treatments. RESULTS: Patients (55% of total) reported overall satisfaction
      with the treatments, and 63% of patients thought they needed additional laser
      treatments, including for maintenance. Subjects (25%) reported that the laser
      treatments were better than any other treatment they had tried. Adverse effects
      were mild and had either disappeared or were significantly decreased in 86% of
      patients. Self reported length of remission compared favorably to those for other
      therapies for localized disease. CONCLUSIONS: UVB laser treatments provide a well
      tolerated means to clear psoriasis plaques. The treatment provides a high level
      of patient satisfaction.

PMID- 12224093
TI  - Treatment of spider leg veins with the KTP (532 nm) laser--a prospective study.
AB  - BACKGROUND AND OBJECTIVES: Spider leg veins are telangiectasias located
      intracutaneously. This condition poses a cosmetic problem. STUDY DESIGN/PATIENTS
      AND METHODS: The purpose of this study was to determine what influence the KTP
      (532 nm) laser has on spider leg veins dependent on the vascular diameter and to
      what extent the skin has been affected. Seventy female patients were treated in
      three laser sessions. Analysis was done 30 weeks after the last laser treatment
      session. RESULTS: Fifty-six patients completed the study. In group 1 (vascular
      diameter < or = 0.6 mm), spider leg veins were no longer visible in 33%; in 40%,
      a decrease in vascular diameter could be observed; in 27%, no change in size
      occurred. In group 2 (vascular diameter 0.7-1.0 mm), laser-treated spider leg
      veins were visible in all patients. Hyperpigmentation occurred in 13 patients.
      CONCLUSIONS: The KTP (532 nm) laser is an effective for treating spider leg veins
      having a vascular diameter under 0.7 mm.

PMID- 12224095
TI  - Photomechanical delivery of 100-nm microspheres through the stratum corneum:
      implications for transdermal drug delivery.
AB  - BACKGROUND AND OBJECTIVES: Photomechanical waves (PWs) render the stratum corneum
      permeable and allow molecules to diffuse into the epidermis. The aim of this
      study was to investigate the probe size that could be delivered through the
      stratum corneum and into the epidermis. STUDY DESIGN/MATERIALS AND METHODS: A
      single PW was applied onto the rat skin in vivo. Aqueous suspensions of
      fluorescent microspheres, 100 nm in diameter, were used as probes for transdermal
      delivery. The presence of the microspheres in the epidermis was measured by a
      fiber-based spectrofluorimeter after the stratum corneum was removed by tape
      stripping (TS). RESULTS: Exposure of the rat skin to a PW permeabilized the
      stratum corneum and allowed the fluorescent microspheres to diffuse into the
      epidermis. CONCLUSIONS: The experiments show that PWs can facilitate the delivery
      of very large molecules and probes into the epidermis.

PMID- 12224096
TI  - Airflow through the auxiliary line of the laser fiber prevents ignition of intra
      airway fire during endoscopic laser surgery.
AB  - BACKGROUND AND OBJECTIVES: Ignition accidents during bronchoscopic laser
      irradiation have occasionally been reported, but the mechanisms responsible for
      the ignition accidents are not fully understood. We examined causative factors
      including ignition site, oxygen concentration, and role of airflow through the
      laser fiber. STUDY DESIGN/MATERIALS AND METHODS: Porcine muscle tissue was placed
      in a bottle and irradiated by laser under various conditions. Also, a piece of
      porcine muscle was wedged in a main bronchus of the isolated porcine lungs and
      irradiated by laser in the same way. RESULTS: Flashing occurred on the tissue
      exposed to the laser, and this flashing reached the ignition when the oxygen
      concentration was above 30%. Increasing airflow through the laser fiber prevented
      the ignition even at an oxygen concentration at 100%. CONCLUSIONS: In laser
      irradiation, the tissue exposed to the laser can be the ignition site of fire.
      Increasing airflow through the laser fiber was an effective technique to prevent
      airway fire.

PMID- 12224097
TI  - Quantitation of calcitonin gene-related peptide mRNA and neuronal cell death in
      facial motor nuclei following axotomy and 633 nm low power laser treatment.
AB  - BACKGROUND AND OBJECTIVES: A persistent increase in calcitonin gene-related
      peptide (CGRP) immunoreactivity in motoneurons may serve as an indicator for
      regeneration after peripheral nerve injury [Borke et al., J Neurocytol
      1993;22:141-153]. STUDY DESIGN/MATERIALS AND METHODS: We examined the effects of
      low power laser treatment (633 nm) on axotomy-induced changes in alpha-CGRP mRNA
      and long-term neuronal survival in facial motoneurons. A quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) assay for alpha-CGRP mRNA was
      used to detect changes in the response to axotomy and laser irradiation. Cell
      counts of neurons in injured and non-injured facial motor nuclei of laser-treated
      and non-treated rats were done to estimate neuronal survival. RESULTS: A 10-fold
      increase (P < 0.0001) in mRNA for alpha-CGRP at 11 days post-transection and an
      almost threefold increase (P < 0.0001) in neuronal survival at 6-9 months post
      transection were found in 633 nm light treated rats. DISCUSSION: These findings
      demonstrate that 633 nm laser light upregulates CGRP mRNA and support the theory
      that laser irradiation increases the rate of regeneration, target reinnervation,
      and neuronal survival of the axotomized neuron.

PMID- 12224098
TI  - International group reiterates stance against human organ trafficking.

PMID- 12224099
TI  - More on the consultant contract. Consultants are at risk of losing both
      independence and democratic rights.

PMID- 12224100
TI  - More on the consultant contract. Consultants should assess the detail of new
      contract.

PMID- 12224101
TI  - More on the consultant contract. What about consultants in frontline specialties?
      . . .

PMID- 12224102
TI  - More on the consultant contract. . . . And what about the teaching role of
      consultants?

PMID- 12224103
TI  - More on the consultant contract. Consultants need to take the lead in using funds
      for stimulating new ways of working . . .

PMID- 12224104
TI  - More on the consultant contract. . . . and in job planning.

PMID- 12224105
TI  - Telephone use in primary care. Telephones have proved useful in managing cystic
      fibrosis.

PMID- 12224106
TI  - AHA pushes regulation for specialty hospitals.

PMID- 12224108
TI  - In accordance but...Premier, Novation take different compliance paths.

PMID- 12224107
TI  - Just passing through. Newly approved drugs' fate dependent on regulation.

PMID- 12224109
TI  - Beneficiaries sue HHS, CMS.

PMID- 12224110
TI  - Demanding demand. VA secretary defends move to stem enrollee volume.

PMID- 12224111
TI  - Nurses are necessary. JCAHO report links staffing, safety.

PMID- 12224112
TI  - War of attrition. Turnover rates for hospital jobs reaching crisis proportions,
      study warns.

PMID- 12224113
TI  - Settlement terms. Ark. chain to pay $2 million to settle elder-abuse case.

PMID- 12224114
TI  - Better safe than sorry. Government gives D.C. hospital $2.5 million for
      bioterrorism preparedness.

PMID- 12224115
TI  - Lots of drama, little action. Drug benefit, provider relief victims of factional
      divisions in Congress.

PMID- 12224116
TI  - Slow growing. Planetree philosophy sprouts new branches of support but remains on
      the healthcare periphery.

PMID- 12224117
TI  - Trickle-down theory. Anthem's expensive acquisition of Trigon Healthcare raises
      question of whether local providers may end up with the bill.
AB  - Anthem's acquisition of Trigon Healthcare, its largest deal to date at $4 billion
      in cash and stock, gives the insurer a sturdy foothold in the Southeast while
      rewarding Trigon's shareholders with a profit. Anthem CEO Larry Glasscock (right)
      and Trigon CEO Thomas Snead expect a smooth transition. Anthem has taken a pricey
      step toward becoming the No. 1 Blues plan consolidator. But will local providers
      end up footing much of the bill?

PMID- 12224118
TI  - IMPACT seeks breakthrough improvements in quality.
AB  - Patient safety, flow, and office procedures are among key areas targeted. The
      Institute for Healthcare Improvement will provide faculty to help analyze results
      of QI projects. Collaborative, results-oriented group is seeking innovators for
      members.

PMID- 12224119
TI  - A positive sentinel event? A says it's possible.
AB  - Identifying the process increases the likelihood of recreating success stories.
      Emphasizing good performance boosts morale, and aids recruitment and retention.
      Learned processes can be transported to other areas of the hospital.

PMID- 12224120
TI  - Poor communication is common cause of errors.
AB  - Identification of root causes, recommended strategies are at odds. The Joint
      Commission on Accreditation of Healthcare Organizations offers its own strategies
      for improving communications. Limiting verbal orders and strict read-back
      protocols can reduce errors.

PMID- 12224121
TI  - Program delays disability in the chronically ill.
AB  - Program teaches participants skills for addressing several different diseases.
      Patients save $400 to $500 over a two-year period by limiting visits. Course is
      taught by lay leaders in hospitals, churches, and community centers.

PMID- 12224122
TI  - Use strategic thinking to avoid unanticipated results.
AB  - Single-mindedness can lead to unintended, and detrimental, results. Environment
      can seem to drive positive changes but yield negative outcomes. Having a larger
      nursing staff can improve financial performance.

PMID- 12224123
TI  - Personality disorders and the duration of depressive episode: a retrospective
      study.
AB  - In the present report from the Rhode Island Methods to Improve Diagnostic
      Assessment and Services (MIDAS) project we examined the relationship between
      chronicity of depression and personality disorders. Three hundred and eighty-five
      depressed outpatients were evaluated with semi-structured interviews. Duration of
      depression was analyzed as a continuous variable, and by subdividing patients by
      the DSM-IV (APA, 1994) chronic specifier (i.e., more or less than 2 years). Two
      separate regression analyses addressed the association between major depressive
      episode duration and each of the ten personality disorders found on Axis II.
      Although there was some difference between particular personality disorders
      associated with the two indicators of depressive duration, the results of the
      regression analyses indicate that the chronicity of depression is associated with
      personality disorders.

PMID- 12224124
TI  - Validation of the dimensional factor structure of the personality psychopathology
      five in clinical and nonclinical samples.
AB  - Confirmatory factor analysis (CFA) was used to determine whether the latent
      structure underlying the items composing the MMPI-2 Personality Psychopathology
      Five scales (PSY-5; Harkness, McNulty, & Ben-Porath, 1995) is representative of
      the theoretical model that informed their construction. Results from the CFA
      revealed a good fit between the hypothesized five-factor model and the obtained
      latent factor structure in both clinical (n = 284) and nonclinical (n = 351)
      samples. Moreover, the PSY-5 model proved to be a better fit than a random five
      factor model and a one-factor model. Correlations between the PSY-5 scales and a
      set of MMPI-2 (DSM-IV) personality disorder scales provided additional evidence
      of convergent and discriminant validity.

PMID- 12224125
TI  - Assessing the DSM-IV structure of personality disorder with a sample of Chinese
      psychiatric patients.
AB  - The validity of the three-cluster system of personality disorders (PDs) in the
      latest version of the Diagnostic and Statistical Manual of Mental Disorders (DSM
      IV; APA, 1994) was examined in a sample of Chinese psychiatric patients (n =
      227), who completed the self-report Personality Disorders Questionnaire for DSM
      IV (PDQ-4; Hyler, 1994) and who were also administered the clinician-rated
      Personality Disorders Interview-IV (PDI-IV; Widiger, Mangine, Corbit, Ellis, &
      Thomas,). Using confirmatory factor analysis, a three-factor model corresponding
      to the DSM-IV clusters was tested and compared statistically to a one-factor
      model and a set of random, three-factor models. Only the clinician-rated
      instrument supported the DSM-IV three-cluster model, and then only when the
      factors were allowed to correlate. Results from the theoretically more rigorous
      uncorrelated model testing did not support the DSM-IV model for either assessment
      modality.

PMID- 12224126
TI  - Self-harming behavior of a parent with borderline personality disorder assessed
      using revealed preference and attributional approaches: a case study.
AB  - This article discusses a case study involving a parent with Borderline
      Personality Disorder who exhibited self-harming behaviors. Assessment and
      intervention were based both on a review of the client's attributions about
      causes of her own behavior as being either internalizing or externalizing, and on
      a review of motivation of the behaviors using functional analysis. Antecedent
      situations for self-harming behaviors were identified to provide a basis for
      reviewing the client's attributions of reasons for disordered behavior. A new
      technique of functional analysis was applied using the principle of revealed
      preference arising from behavioral economics. Revealed preference identified
      outcomes that were valued by the client, enabling new responses to be identified
      to attain these reinforcers. Attribution re-training was provided. Significant
      reductions in self-harming behaviors were achieved during brief therapy and were
      maintained during follow-up.

PMID- 12224127
TI  - Measuring the core features of personality disorders in substance abusers using
      the Temperament and Character Inventory (TCI).
AB  - Personality disorders (PDs) are still classified through categorical taxonomies
      that are at odds with current research findings. Dimensional models provide a
      suitable alternative for measuring individual differences. However, as they have
      traditionally lacked a clear definition of the "disorder" construct, the clinical
      utility of these models has been limited. This study tests whether Cloninger's
      dimensional model is able to capture two domains: the features that differentiate
      PD subtypes from each other and the common core features underlying all PDs.
      Seventy-four drug dependent patients were independently assessed using the SCID
      II and Cloninger's TCI. There was a slight relationship between TCI temperament
      dimensions and the DSM personality disorder subtypes, but the association was not
      specific enough to allow differential diagnosis. The character dimension Self
      Directedness was strongly associated with the presence and severity of all PDs,
      irrespective of subtype, correctly classifying 77% of subjects. Character
      dimensions are a reliable, valid and low-cost tool for detecting PDs in drug
      abusers and may help to provide an operational definition of the common core
      features underlying all PDs.

PMID- 12224128
TI  - The prediction of violent and nonviolent criminal behavior in a methadone
      maintenance population.
AB  - The utility of traits associated with Antisocial Personality Disorder in making
      risk assessments of violent and nonviolent crimes was examined in 254 subjects
      sampled from a methadone maintenance population. A factor analysis of a number of
      baseline measures resulted in five factors measuring hostility, insecure
      attachment, impaired reality testing, antisocial personality, and empathy. These
      factors were used in logistic regression analysis to predict charges for violent
      and nonviolent crimes over a 2-year period. Individuals with high scores on the
      antisocial personality factor had an increased risk of both violent and
      nonviolent criminal charges. Individuals with low scores on the empathy factor
      were at high risk for violent crimes. In an analysis using the factor components
      rather than the factors, the measures of perspective-taking and a socialization
      were associated with violent criminal charges, and the measure of psychopathy,
      but not antisocial behavior, was associated with nonviolent criminal charges. The
      results support the use of measures of personality traits in addition to measures
      of a history of antisocial behavior in making violence risk assessments in
      substance-dependent patients. The DSM construct and diagnosis of Antisocial
      Personality Disorder may be enhanced by greater emphasis on personality traits
      associated with antisocial behavior.

PMID- 12224129
TI  - Factor analyses of the DIB-R in adolescents.
AB  - The goal of this study was to examine the factor structure of the Revised
      Diagnostic Interview for Borderlines (DIB-R; Zanarini, Gunderson, Franckenburg, &
      Chauncey, 1989) in a nonpatient sample of 118 adolescents. A principal components
      factor analysis with a Varimax rotation extracted three factors. A confirmatory
      factor analysis showed that this three-factor model provided an adequate fit. The
      first factor, which included depression, anxiety, helplessness/hopelessness,
      loneliness/emptiness, and also encompassed odd thinking/unusual perceptive
      experiences and quasi-psychotic experiences, appeared to be centered on painful
      feelings and dissociative defense. The second factor, labeled "impulsivity,"
      consisted of impulse action patterns, counterdependency, and stormy
      relationships. This factor seemed to be centered on defensive acting-out. The
      third factor, called "aggressiveness," consisted of anger, hypomania,
      devaluation/manipulation/sadism, and demand/entitlement, and might express
      manic/narcissistic defenses. These analyses suggest that there may be homogeneous
      components of borderline symptomatology in adolescents that may reflect affective
      disturbances and defensive mechanisms.

PMID- 12224130
TI  - Establishment and characterization of a new osteogenic cell line (MOS-J) from a
      spontaneous C57BL/6J mouse osteosarcoma.
AB  - In this paper we describe the establishment and characterization of a
      transplantable cell line derived from a spontaneously occurring chondroblastic
      osteosarcoma in a C57BL/6J mouse. The tumor line, MOS-J, forms solid tumors when
      injected intramuscularly into immunocompetent syngeneic hosts, mimicking
      endochondral bone development. These transplantable tumors have the capacity to
      destroy and invade existing bone and invade vessels in close proximity to the
      tumor. In culture, MOS-J cells form layers of pleomorphic cells with high mitotic
      activity. These cells have marked alkaline phosphatase activity and form
      calcified foci in vitro that stain with alizarin red. MOS-J cells also promote
      osteoclast development in vitro from normal bone marrow cells. These
      characteristics indicate the potential utility of the MOS-J osteosarcoma cell
      line as a model for studies of human osteosarcoma and bone biology.

PMID- 12224131
TI  - Local tolerance to spider silks and protein polymers in vivo.
AB  - Spider silks were implanted subcutaneously in pigs for a study of the tolerance
      against this material. Four types of spider silks of high purity and cleanliness
      were implanted: (i) major ampullate dragline silk reeled from the golden silk
      spider Nephila clavipes, (ii) native (unsterilised) silk reeled from a
      Brachypelma spider, (iii) native silk taken from this spider's web and (iv) its
      web silk thermally treated at 80 degrees C. For comparison we used fibrous silk
      analogue protein polymers and four already marketed wound dressings (polyurethane
      film, collagen dressings, gauze pads). All materials were applied epicutaneously
      to split skin wounds. The implants were examined macroscopically as well as by
      light microscopy. Superficially, all sites healed rapidly. There were marked
      inflammatory reactions in all sites with lympho-plasmacellular infiltrations,
      evidence of phagocytosis and granuloma formation as indicated by the appearance
      of giant cells. However there was a marked absence of epitheloid cells indicating
      that the observed reaction was a foreign body granuloma. Furthermore, the
      histopathological images recorded after 14 days revealed no marked differences
      between the dressings. Polyurethane films, however, seemed to be superior with
      respect to the duration of the wound healing process.

PMID- 12224132
TI  - Apoptotic colon disease: a new clinico-pathological entity.
AB  - A patient with intractable diarrhea showed, in 6 out of 7 biopsies taken at
      various colonic levels, a rich number of apoptotic granules at the base of the
      colonic crypts. Those apoptotic granules stained positive with Feulgen, a
      reaction that stains nuclear DNA. The nuclei of the cells at the base of the
      crypts stained positive with TUNEL, a method that labels nuclei undergoing
      apoptosis. No associated inflammatory reaction was present in the biopsies. As no
      other explanation was found for the phenomenon, the possibility that marked
      cryptal apoptosis was the cause of the untreatable protracted diarrhea was
      entertained. A similar histological finding had previously been recorded in a non
      human primate dying of intractable diarrhea. That phenomenon was designated
      apoptotic colonic disease. We propose a similar denomination for this previously
      unreported finding in a human subject.

PMID- 12224133
TI  - Bioinformatics-based discovery of a novel factor with apparent specificity to
      colon cancer.
AB  - In a previous study, a data mining tool called Digital Differential Display (DDD)
      from the Cancer Genome Anatomy Project (CGAP) was used to predict solid tumor-
      and organ-specific genes from the expressed sequence tag (EST) database. To
      validate the use of bioinformatics approaches in gene discovery, one of the ESTs,
      which was predicted to be colon tumor-specific, was chosen for further study.
      Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) analysis of matched sets
      of cDNAs from normal and colon tumor tissues indicated that the EST was
      specifically expressed in the majority of colon tumors. Expression was also
      detected in early adenomas. Among other normal tissues, EST expression was
      detected only in the small intestine. The colon tumor specificity of this EST was
      inferred from the lack of expression in carcinomas of the breast, lung, ovary,
      pancreas and prostate. To validate the computational prediction of specificity, a
      full-length cDNA encompassing the entire open reading frame was cloned and, in
      view of its apparent specificity to the colon tumors, this gene was termed Colon
      Carcinoma Related Gene (CCRG). CCRG encodes a novel cysteine-rich motif and a
      putative signal peptide sequence. Supernatant from COS cells transfected with the
      CCRG expression vector stimulated proliferation of colon cancer cells.
      Immunoreactive CCRG was also detected in the paraffin sections of colon tumor
      samples. CCRG belongs to a new class of growth factors and may be important in
      the diagnosis and treatment of colon cancers. Identification of CCRG using
      bioinformatics approaches validates gene discovery using computational
      approaches.

PMID- 12224134
TI  - Abdominal and pelvic extra-adrenal paraganglioma: a review of literature and a
      report on 7 cases.
AB  - INTRODUCTION: Extra-adrenal paraganglioma (pheochromocytoma) is a rare tumor.
      Herein we describe the clinical and pathological findings in patients with
      paragangliomas of the urinary bladder, seminal vesicle and retroperitoneum.
      METHODS: Between January 1994 and January 2001, extra-adrenal paragangliomas were
      diagnosed in 7 patients: 3 males and 4 females. The mean age of our patients was
      32 +/- 15.9 years. We reviewed the clinical data. Urinary metanephrines and
      vanillyl mandelic acid and blood catecholamine levels were estimated in 4 cases.
      CT scan and/or MRI were used in the imaging of all cases. 123I-MIBG was used in
      only 1 patient, who harbored multiple tumors. All the patients but one underwent
      surgical treatment. RESULTS: The definitive diagnosis was made by
      histopathological examination of the removed tumors and was confirmed in all
      cases by the immunohistochemical stains of chromogranin A and S100 protein. There
      was metastasis in the pelvic lymph nodes in 1 patient. Follow-up ranged from 3 to
      82 months (mean = 37.9 +/- 25.8). The catecholamine level was elevated in 3
      patients under basal conditions and during endoscopic resection of the tumor in a
      fourth patient. In all cases, the catecholamine level was normalized after
      surgery. There was no recurrence or metastasis in any case following surgery.
      CONCLUSION: Pre-operative diagnosis of nonfunctioning bladder paraganglioma is
      difficult, but the tumors should be suspected in patients who have hypertension,
      hematuria or mass effects due to the tumor growth in the pelvis and/or
      retroperitoneum. Six of the seven cases reported here were found in the usual
      locations: 3 in the urinary bladder, 2 in the renal hilum and 1 in the organ of
      Zuckerkandl. One patient had multiple tumors, including a paraganglioma of the
      seminal vesicles. Resection is the treatment of choice, and in the case of
      urinary bladder paraganglioma should include total cystectomy. In patients with
      unresectable multiple tumors, medical therapy may be used to control
      hypertension.

PMID- 12224135
TI  - A line of Berlin Druckrey IV rats proposed as a new model for human hereditary
      ataxia.
AB  - An experimental colony of Berlin Druckrey IV (BD IV) rats with inherited,
      congenital, gradually progressive incoordination and rear limb ataxia was
      evaluated for clinical signs, gross and microscopic nervous system lesions, and
      mode of inheritance of the gene defect. Clinical evaluation suggested a lesion in
      the midbrain or brainstem, with resulting lower motor neuron functional
      impairment. Gross alterations in affected rats were atrophy of thigh musculature
      by six months of age and thoracic kyphoscoliosis. Histological evaluation of the
      nervous system revealed central chromatolysis of neurons within the red nuclei in
      20 out of 24 affected rats. Additionally, in six out of 24 affected rats
      chromatolytic neural cell bodies of this nucleus contained brightly eosinophilic,
      coarsely granular, cytoplasmic deposits. Special stains (osmium tetroxide,
      Kinyoun's acid-fast and periodic acid-Schiff) indicated these deposits consisted
      of lipopolysaccharide. Additional lesions in ataxic rats included qualitative
      reduction in neuronal cell bodies of the inferior olivary nucleus (10 out of 26
      rats) and cerebellar Purkinje cells (5 out of 27 rats). No reduction in the
      number of spinal cord lower motor neurons was detected. Analysis of intercross
      pedigrees that were established between ataxic BD IV females and either normal
      Long Evans or Fisher males indicated a likely autosomal recessive mode of
      inheritance. The authors propose that this disease accompanying a new variant of
      the BD IV rat (to be designated "shaker" rat) provides a new and unique research
      model for ataxia with features in common with some human hereditary ataxias.

PMID- 12224136
TI  - The impact of progesterone receptor expression on relapse in the long-term
      clinical course of 93 benign meningiomas.
AB  - BACKGROUND: Previous clinicopathological observations have pointed towards an
      impact of progesterone receptor (PgR) expression on the clinical course of
      meningiomas. MATERIALS AND METHODS: EXpression of PgR and the proliferation
      marker MIB-1 was assessed by immunohistochemistry in the primary tumours of 30
      cases of benign, completely resected, recurrent meningiomas and compared with 63
      cases of meningioma without recurrence for 14 or more years. RESULTS: Univariate
      analysis showed a significantly higher risk for recurrence (odds ratio 3.533) for
      tumours with a low expression of PgR. A tendency for a higher risk for tumours
      with higher proliferation rate (odds ratio 6.889) was not significant. In 20
      cases in which the primary tumour could be compared with its recurrence, no
      consistent changes of PgR expression were observed. CONCLUSION: Our findings
      support previous studies that found an association of low or absent expression of
      PgR with a higher risk of recurrence. This encourages attempts at a hormonal
      therapy for patients with PgR-positive meningioma.

PMID- 12224137
TI  - Cell proliferation and DNA fragmentation (apoptosis) on FNABs of breast invasive
      ductal carcinomas and their relationship to clinicopathological variables and
      prognosis.
AB  - The purpose of this study was to investigate cell proliferation and apoptosis in
      ductal breast invasive carcinomas and their relationship to prognosis. Fifty
      cases, from the same number of operable female patients, were diagnosed
      cytologically on FNA biopsies as invasive ductal breast carcinomas and confirmed
      histologically after oncectomy. In the same cases, to evaluate the cell
      proliferation and apoptosis, the MIB1 and the TUNEL method were used
      respectively. Furthermore the relationship between proliferative activity and
      apoptosis to other factors such as menopausal status, tumor size, axillary lymph
      node status and tumor grade was studied. Cell proliferation and apoptosis were
      found to be significantly related to the menopausal status of the patients (p <
      0.001) and to the grade of the tumor (p < 0.01), while no significant
      relationship to axillary lymph node status and tumor size was found.

PMID- 12224138
TI  - Splenectomy, chemically-induced mammary tumors and parathymic lymph nodes in
      rats: experimental and morphological studies.
AB  - The objective of this study was to examine whether splenectomy alters the
      tumorigenic response of rats to chemically-induced mammary tumors and to
      determine the role played by the parathymic lymph nodes (PTLN) in the antitumor
      immune response. Female rats were splenectomized and then exposed to 9,10
      dimethyl-1,2-benz(a)anthracene (DMBA) to induce mammary tumors. Splenectomy
      decreased the rate of tumor appearance. The latent period for appearance of the
      first tumors in splenectomized rats was 12.0 +/- 0.9 week compared to 9.7 +/- 0.5
      week in intact controls. The latent periods for appearance of all tumors
      including those with malignancy were similar for both rat groups. Splenectomy
      caused a significant increase in the size of the PTLN as well as changes in their
      structure. The cortex became thick, better formed and enriched with lymph
      elements of follicles and a wide venous net. CD8+ cells infiltrated the
      paracortex whereas CD4+ cells were located around the blood vessels. In
      conclusion, splenectomy inhibits the early stages of tumorigenesis, but does not
      prevent the progress of carcinogenesis. Different responses of splenectomized
      (operated) and intact rats to the effect of DMBA can be explained by an increase
      in the nonspecific resistance of splenectomized rats as a result of the
      operation. PTLN actively participate in this compensatory reaction of the immune
      system of animals.

PMID- 12224139
TI  - [Digoxin dosing: the habitual and the optimal thing].

PMID- 12224140
TI  - [Best result of digoxin dosing in the aged by taking into account that both the
      elimination as well as the volume of distribution of the drug decrease when the
      kidney function deteriorates].
AB  - PURPOSE: To evaluate three methods for digoxin dose adjustment in aged patients.
      METHODS: We determined the plasma digoxin levels that would be attained in 87 old
      patients with doses adjusted to the kidney function by means of three separate
      procedures. RESULTS: Age: 79.0 "6.3 years of age; creatinin clearance (Clc):
      0.70" 0.23 ml/Kg of lean body weight and minute. Only the methods that adjust
      both the digoxin clearance and the volume of distribution to the Clc achieve the
      independence between the digoxinemia and the kidney function. The best of them,
      by calculating the elimination constant (K) and the volume of distribution (V) as
      linear functions of the Clc, so that K ranges between 0.173 and 0.462 days-1 and
      V between 4 and 10 l/Kg of lean body weight when the Clc varies from 0 to 110
      ml/minute, achieve digoxinemia figures between 0.8 y 2.0 ng/ml and above 2.0
      ng/ml in the 81.6% and 0.0% of the patients (95% confidence intervals (95% CI):
      72.2% to 88.4 and 0.0% to 4.6%), respectively; with a precision and a bias of
      0.43 and -0.06 ng/ml (95% CI: 0.38 to 0.48 and -0.16 to 0.03 ng/ml),
      respectively. CONCLUSION: The described method would lead to good results if
      digoxin has not been prescribed in order to control the cardiac frequency in the
      setting of auricular fibrilation.

PMID- 12224141
TI  - [Mortality in a cohort of patients with type 2 diabetes mellitus in Alcaniz,
      Spain].
AB  - OBJECTIVE: The aim of this study was to compare the mortality rate of type 2
      diabetic patients with the mortality rate of the background population. Also was
      assessed the impact of baseline variables on mortality. METHODS: Prospective
      cohort study. Patients with type 2 diabetes were included from june 1994 to june
      1998. The life status was ascertained on october 2001. Excess mortality, compared
      with the background population, was assessed in terms of standardised mortality
      ratio (SMR) for the whole group, for males and for females. The Cox's model was
      used to investigate the influence of baseline risk factors on mortality. RESULTS:
      463 patients were included. The mean follow-up was of 5 years. The life status
      was ascertained for the 99% of the cohort. The mortality rate of the whole group
      was 21.75 per 1000 (31.4 per 1000 males and 16.4 per 1000 females). The SMR of
      the whole group was 147% (IC 95%: 109-194; p < 0.05), the SMR of males 167% (IC
      95%: 107-246; p < 0.05) and the SMR of females 147% (IC 95%: 95-217; p = ns). The
      independent predictors of early mortality on multivariate survival analysis were
      age (HR = 1.13; IC 95%: 1.08-1.18; p < 0.0001) and proteinuria (HR = 4.72; IC
      95%: 2.15-10.35; p = 0.0001). CONCLUSIONS: Diabetic patients in our population
      have increased their mortality risk in 47%. The main risk factor of mortality was
      the presence of proteinuria.

PMID- 12224142
TI  - [Development of pre-hepatic portal hypertension of the rat].
AB  - OBJECTIVE: A long-term study of the prehepatic portal hypertension model by
      triple stenosing ligation of the portal vein in the rat. METHOD: A cluster
      analysis of the animals in the different evolutive stages of portal hypertension
      (1 1/2, 6, 12 and 14 months) has been carried out. This analysis has made it
      possible to identify three homogeneous groups (A, B and C) in relationship to the
      liver weight. RESULTS: The animals with liver atrophy (group C) show a decrease
      of body, splenic and testicular weights as well as a higher development of the
      portosystemic collateral circulation in relation to the A and B groups.
      CONCLUSION: The percentage of animals belonging to the group C decrease
      progressively during the evolution of portal hypertension and those animals
      corresponding to the group A, in which is superior the liver weight, increase,
      while the B group does not change.

PMID- 12224143
TI  - [Description of the von Hippel-Lindau disease in three spanish families].
AB  - PURPOSE: To describe disease evolution and clinical follow-up of 10 patients in
      three Spanish families. PATIENTS AND METHODS: Patients were contacted through the
      von Hippel-Lindau Family Alliance (VHLFA). Compilation of medical reports and
      patient interviews were carried out in May of 2001. This is a retrospective study
      of a case series. RESULTS: Family history was suggestive of von Hippel-Lindau
      disease in two of the families. A 'de novo' mutation is described in the third
      family. The mean patient age is 30.8 (range: 15-53). The age of presentation was
      < 30 in 9 patients. In 8 of the patients, eye involvement was the first VHL
      presentation. 7 patients currently have hemangioblastomas of the CNS. Most
      patients are not participants in management protocols for the coordinate care of
      their various VHL lesions. 6 patients had documented pancreatic involvement and 3
      patients had renal cancer. Clinical screening for occult pheochromocytomas were
      performed in 5 patients. 4 were deceased from VHL-related complication. Genetic
      studies had been performed in 4 of the 6 survivors. CONCLUSIONS: Disease
      progression in our series is similar to that previously described for other
      families. Diagnosis was delayed in two of the families. Suboptimal patient
      management may have contributed to the high morbidity and mortality.

PMID- 12224144
TI  - [Lung hypoplasia in the adult: description, pathogenesis and review].
AB  - The lung hypoplasia is a very few frequent entity characterized by a detention in
      the lung development that leads to a poor development of this organ. Habitually
      this disease is diagnosed in the childhood and there are very few cases that pass
      unknown, being detected in the mature age (> 18 years). We present four cases of
      diagnoses adult patients of lung hypoplasia for diverse test (imaging or
      invasive) that consulted for not specific symptoms, mostly related with
      infections of the lung and their later evolution over the years. We also review
      the pathogenesis, etiology and malformations associated of this disease as well
      as a review of the published articles in this age group.

PMID- 12224145
TI  - [Eosinophilic gastroenteritis: clinical spectrum of the same disease].
AB  - Eosinophilic gastroenteritis is a condition of unknown etiopathogenesis and
      unusual description. Clinical symptoms are widely diverse ranging from mild
      episodes of abdominal discomfort to acute intestinal obstruction which leads
      occasionally to urgent surgical approach. This wide range of clinical
      possibilities seems to be secondary to the rate of eosinophilic infiltration of
      the bowel wall and the number of layers involved. We report two cases showing
      that anatomo-clinical variety and their therapeutic outcomes.

PMID- 12224146
TI  - [Cocaine related fulminant liver failure].
AB  - A 23-year-old woman developed biochemical signs of acute severe hepatitis
      together with confusion and flapping tremor after snorting a large dose of
      cocaine. Blood levels of cocaine were very high and liver biopsy performed few
      days later showed centrilobular necrosis. She recovered completely with
      conservative measures. Cocaine toxicity should be considered in similar cases of
      fulminant liver failure.

PMID- 12224147
TI  - [Use of beta-blockers for treatment of cardiac failure].
AB  - The rationale for betablocker use in heart failure, based on neurohormonal
      physiology, has been established over the past 20 years. Recent trials have shown
      the unequivocal benefits of betablockers in patients with chronic systolic heart
      failure. The benefits include improve survival (35%) reduced need for
      hospitalization and improve of left ventricular function. However, betablockers
      may also make a patient with heart failure worse, especially when treatment
      begins and there is reluctance to use betablockade therapy. Complications can
      generally be avoided by starting with extremely low doses and increasing the dose
      very slowly. Despite this, further questions remain regarding the use of these
      agents in cardiac failure, including the role in the progression of the disease,
      the selection of individual betablocker, and the use in very severe disease or
      very old patients.

PMID- 12224148
TI  - [Algodystrophy in the post-partum].

PMID- 12224149
TI  - [Severe neutropenia induced by ticlopidine. Presentation of two cases and review
      of the literature].

PMID- 12224150
TI  - [Multicentric leiomyosarcoma in a patient with HIV infection].

PMID- 12224151
TI  - [Spontaneous pneumomediastinum associated with anxiety state].

PMID- 12224152
TI  - [Thrombocytopenic purpura associated to Mycoplasma pneumoniae infection in an
      adult patient].

PMID- 12224153
TI  - [Progressive icterus in a 56 years old man].

PMID- 12224154
TI  - [Disseminated infection by Mycobacterium scrofulaceum in an infected HIV
      patient].

PMID- 12224155
TI  - [Metabolic alkalosis due to bicarbonate ingestion].

PMID- 12224156
TI  - [Correction of the treatment of bacteremia].

PMID- 12224157
TI  - [Laparoscopic surgery. Should everything be done that can be done? Or the test of
      time].

PMID- 12224158
TI  - Laparoscopic nephroureterectomy for upper tract transitional cell carcinoma.
AB  - OBJECTIVE: The standard surgical treatment of upper tract TCC remains
      nephroureterectomy with excision of a cuff of bladder. However, laparoscopic
      nephroureterectomy (LNU) has been shown to be associated with reduced
      perioperative morbidity, a shorter hospital stay, and a reduced requirement for
      transfusion than open nephroureterectomy (ONU). The objective of this article is
      to review experience and outcome following laparoscopic nephroureterectomy for
      upper tract TCC. METHOD: A literature search of PubMed
      (www.ncbi.nlm.nih.gov/PubMed/) was performed and articles reporting technical
      aspects and outcome of laparoscopic nephroureterectomy for upper tract TCC were
      reviewed. RESULTS: The published data show that outcomes reported following LNU
      in terms of cancer control are comparable to ONU, at least in the short to medium
      term. Despite concerns about port site recurrences there were no incidences of
      this in the 125 patients undergoing LNU in the reviewed reports. An interesting
      observation was that a high percentage of the tumours are Grade 2 or 3 when TCC
      affects the upper tract, unlike TCC of the bladder where the majority of tumours
      are of low grade and stage. CONCLUSION: Laparoscopic nephroureterectomy is a safe
      treatment option for patients with upper tract TCC. The shorter hospital stay and
      faster overall recovery is obviously of benefit to the patient, but importantly
      the longer-term tumour control appears to be equivalent to that following open
      nephroureterectomy.

PMID- 12224159
TI  - Laparoscopic radical prostatectomy: a European virus with global potentials.
AB  - OBJECTIVES: To review the current status of the Laparoscopic Radical
      Prostatectomy in Europe (LRP). METHODS: The published peer reviewed articles on
      the experience of the European groups performing Laparoscopic Radical
      Prostatectomy. RESULTS: Three different approaches have been described for LRP,
      two of them transperitoneally (early dissection of seminal vesicles or of the
      prostatic apex) and one totally extra peritoneally. Results in terms of per
      operative performances and immediate outcomes seem to be comparable with the
      exception of the bleeding and the transfusion rate that seem higher in the
      transperitoneal approach with early dissection of the prostatic apex. Conversion
      rates have been described up to 5% but it is rare after the 20 first cases; after
      the learning curve has been overcome the complication rate varies between 10% and
      17%. Being a novel technique, all the series have a short median follow-up of
      around one year. The one-year continence rates are comparable to the ones
      described with the classical open approach, as it is the potency rate. The rate
      of positive margins bounces between 2 and 49% depending mainly on case selection.
      A long and steady learning curve burdens the technique in terms of complications.
      CONCLUSIONS: LRP is feasible, teachable and reproducible. Although no comparative
      series with the open approach are available yet, functional and oncological
      results seem to be comparable to the ones reached after open Retropubic Radical
      Prostatectomy.

PMID- 12224160
TI  - Robotics, telesurgery and telementoring--their position in modern urological
      laparoscopy.
AB  - OBJECTIVES: Laparoscopic surgery in general is handicapped by the reduction of
      the range of motion from six to four degrees of freedom. This has a major impact
      on technically difficult procedures such as laparoscopic radical prostatectomy.
      Solutions for this problems include the understanding of the geometry of
      laparoscopy with sophisticated training programs, but lie also in newly developed
      surgical robots, computer simulators and telementoring. This article evaluates
      the value of these alternatives based on own experiences and an analysis of the
      current literature. METHODS: Own experiences with robot-assisted surgery include
      406 laparoscopic radical prostatectomies using a voice-controlled camera-arm
      (AESOP) as well as 6 telesurgical interventions with the Da Vinci-system.
      Additionally, substantial experimental studies have been performed focussing on
      the geometry of laparoscopy and new training concepts such as perfused
      pelvitrainers and computer simulation. Moreover, the current literature of the
      last 10 years on telesurgery and telementoring has been reviewed. RESULTS: The
      geometry of laparoscopy includes the angles between the instruments which have to
      be in a range of 25 degrees to 45 degrees; the angles between the instrument and
      the working plane that should not exceed 55 degrees; and the angle between the
      shaft of the needle holder and the needle which has to be adapted according to
      the anatomical situation in range of 90 to 110 degrees. 3-D-systems did not yet
      proved to be effective due to handling problems such as shutter glasses, video
      helmets or reduced brightness. At the moment, there are only two robotic surgical
      systems (ZEUS, Da Vinci) in clinical use for telesurgery, of which only the Da
      Vinci provides stereovision and all six degrees of freedom (DOF). In the
      meantime, more than 200 laparoscopic radical prostatectomies have been performed
      with this system. Until now, however, there was no evidence of any advantages
      over the conventional laparoscopic approach. The ZEUS in combination with the
      telecommunication system SOKRATES is the only device enabling to realize
      telemanipulation and telementoring over long distances (i.e. transatlantic).
      CONCLUSION: Robotic surgery represents a turning point of surgical research.
      However, broad use of robotic systems is limited mainly because of the high
      investment and running costs. Whereas there will be a clear role of audio-visual
      telementoring in future training concepts, the need of
      telemanipulation/telesurgery has not yet been clarified. New technological
      concepts promote the development of hand-held mechanical manipulators (i.e. 6-DOF
      needle-holder) used in combination with mono-tasking computerized robots (i.e.
      AESOP) resulting in a significant cost reduction.

PMID- 12224161
TI  - Laparoscopic retroperitoneal lymph node dissection.
AB  - OBJECTIVES: Primary objective of the present article is to evaluate the surgical
      efficiency of the laparoscopic retroperitoneal lymph node dissection in clinical
      stage I and II testis tumor. Secundary,  objective is the description of the
      technique used by the author. METHODS: A description of the author's experience
      and review of the literature in terms of feasibility, oncological results and
      quality of life. RESULTS: Once the learning curve has been overcome, the
      operative time is in the range of that open surgery with lower morbidity and
      complications. Ejaculation can be preserved in virtually all patients by means of
      a template dissection. With a mean follow-up of almost four years oncologic long
      term outcome is not compromised by the laparoscopic approach. CONCLUSIONS: In
      clinical stage I testis tumor laparoscopic retroperitoneal lymph node dissection
      can be used as a diagnostic measure with the same long term results as the open
      procedure. In stage II disease removal of residual tumor can also be achieved by
      laparoscopy.

PMID- 12224162
TI  - [Treatment of urinary stress incontinence using a laparoscopic technique].
AB  - OBJECTIVES: To evaluate our own experience with laparoscopic bladder neck
      suspension. The laparoscopic procedure is performed by anchoring a mesh from the
      vagina to the ligament, thus creating tension. This technique has several
      characteristics that make it very attractive: it is easy to learn, operating
      times are short and it is a commonly indicated procedure. METHODS: We present a
      series of 72 women with history of urinary stress incontinence to whom a
      laparoscopic bladder neck suspension was indicated. RESULTS: The procedure was
      completed in 69 patients, with a mean operative time of 40 minutes. Mean hospital
      stay was 1.6 days (Range 1 to 5 days). Continence rate was 82% after a median
      follow up of 31 months. 12 patients recurred after the operation, 7 of them
      recurred in the first 2 months and 5 had previous surgical history; this makes us
      think whether the technique was not adequately performed or the indication for
      treatment was not suitable. CONCLUSIONS: We believe that, although it is
      necessary a longer follow-up, laparoscopic bladder neck suspension can be
      considered a good alternative in the treatment of urinary stress incontinence.

PMID- 12224163
TI  - [Training in laparoscopy: from the laboratory to the operating room].
AB  - OBJECTIVES: To review all different steps in the process of learning laparoscopic
      surgery, presenting the guidelines that surgeon and his/her team should follow to
      successfully complete the process. METHODS: We describe two levels of training:
      Basic, that is initiated with handling of instruments in simulators, and
      Advanced, which culminates with the practice of specific procedures in animal
      models. RESULTS: At the basic level eye-hand coordination is acquired through
      exercises under direct vision in mechanical simulators. Later on, the use of
      optic and camera will allow to achieve eye-hand-TV monitor coordination. To use
      experimental and organic tissues permits to practice organic dissection and
      suture. Training at the advanced level is performed in research animals and makes
      up team work. Animal species selection, team composition, and anatomical protocol
      are of utmost importance to successfully complete the second phase. CONCLUSIONS:
      Training in laparoscopic surgery is a complex process that implies surgeon's
      interaction with the rest of the team. Basic and advanced training must be
      available for all team members in order to assure satisfactory results in the
      difficult initial phase that should be mentored by an expert in laparoscopic
      surgery.

PMID- 12224164
TI  - Microlaparoscopic varicocelectomy.
AB  - OBJECTIVES: To review the development of laparoscopic varicocelectomy from our
      initial description in 1986 based in the first pioneering works of K. Semm and to
      describe our latest microlaparoscopic technique that uses 3 mm instruments.
      METHODS: We use 3 mm reusable trocars with a specially designed telescope and
      instruments. One port is in the umbilicus the others are in the flanks at this
      level. Spermatic vessels are identified by firm traction of the testicle. The
      peritoneum is incised transversally at this level to dissect and ligate the two
      or three veins usually found here. To shorten operation time and improve results
      the vascular bundle is ligated en-bloc and when it is bulky, we divide it into
      two smaller bundles before tying the knot. RESULTS: Field of vision and image
      brightness is adequate and allows the operator to suture with great precision and
      ease. Large angular movements of the 3 mm telescope should be made with its
      trocar. Image brightness depends on the proximity of the lens to the structure
      being inspected; it worsens when the lens is withdrawn even slightly. Reusable 3
      mm instruments can be used hundreds of times and with care they have sufficient
      strength to permit tying tight even en-bloc ligatures of vascular bundles.
      Operating times are between 20 and 25 minutes, bilateral operations need about 10
      minutes more. Wounds made by the 3 mm trocars are usually self-closing and rarely
      need to stitch. CONCLUSIONS: Many authors confirm that since we first described
      the technique 15 years ago laparoscopic varicocelectomy is a safe, quick and easy
      minimal invasive procedure, less expensive than open techniques or occlusion
      under radiological control. The Palomo retroperitoneal approach using en-bloc
      ligatures of the vascular pedicle laparoscopically shortens operative times, the
      percentage of failures is minimum and postoperative testicular volumes and sperm
      counts increase. The microlaparoscopic technique not only reduces surgical
      aggression, but also the risk of complications is less and it does not increase
      operative difficulty or operation time.

PMID- 12224166
TI  - [Laparoscopic pyeloplasty].
AB  - OBJECTIVES: To review indications, results and endourologic alternatives to the
      pyeloplasty technique. METHODS: We describe the surgical technique proposed by
      Schluesser et al., which was applied to 9 patients in our series. Another 4
      patients underwent a simple laparoscopic pyelolisis. RESULTS: Results obtained
      with laparoscopic dismembered pyeloplasties are completely comparable with those
      obtained with the conventional Anderson Hynes Pyeloplasty. Outcomes were very
      favourable in 7/9 patients in the series; another one shows a discrete
      improvement and the other one did not return for control. Is does not happen the
      same with pyelo-ureterolysis. Two of them had a good outcome, other two remain
      the same, and another one has not had his control yet. CONCLUSIONS: After 8
      years, laparoscopic pyeloplasty has consolidated as the elective technique in
      cases of recoverable hydronephrosis, secondary to crossing vessels or which have
      a redundant renal pelvis. A few important modifications to the technique have
      been proposed; exceptions are that it can also be done by retroperitoneoscopy and
      that in some cases equally good results may be obtained with the Fenger's
      laparoscopic pyeloplasty.

PMID- 12224165
TI  - [Laparoscopic lymphadenectomy. Current indications].
AB  - OBJECTIVES: To analyse the experience of our own group and other reference groups
      with laparoscopic pelvic lymphadenectomy since 1990 regarding different aspects:
      Technical details, results, complications, and establishment of its current
      indications for prostate cancer treatment. METHODS: We report a retrospective
      statistical analysis of a series of lymphadenectomies over a 10 year period with
      a total of 202 cases (69 laparoscopic and 133 open surgical) analysing different
      lymph node invasion risk factors. RESULTS: Elevated PSA and Gleason resulted in
      more lymph node infiltration being the cutting point in 40 and 7 respectively.
      CONCLUSIONS: Laparoscopic lymphadenectomy provides equal diagnostic reliability
      than the traditional technique. Currently we perform laparoscopic lymphadenectomy
      in prostate cancer for T3 tumours (independently of PSA or Gleason score) and in
      < T3 with PSA > or = 40, Gleason > or = 8, and in cases with Gleason 7 and PSA >
      20.

PMID- 12224167
TI  - [Modified laparoscopic scissors: a new instrument for performing endopyelotomy].
AB  - OBJECTIVE: The safety and success of antegrade endopyelotomy in the treatment of
      ureteropelvic junction (UPJ) stenosis have been documented in numerous literature
      reports over the last decade. We show a new available alternative to the way
      incision is performed. METHODS: Endopyelotomy with modified laparoscopic scissors
      was performed in 18 patients; 12 presented with primary obstruction and 6 with
      secondary obstruction. 3 mm laparoscopic scissors with one end sharpened and
      adapted for this technique are introduced through a nephroscope. A small puncture
      through the renal pelvis wall is made in the posterolateral position using the
      scissors' end. After that, scissors are opened under permanent endoscopic control
      as far as to visualization of the peripyelic space, continuing then with the
      internal edge of the scissors down to the UPJ. Visual control allowed us to
      coagulate any vessel and to avoid the bigger calibre ones. At the end of the
      procedure an endopyelotomy stent was placed over the safety guide wire. RESULTS:
      Results were good in 17 patients (94%); symptomatic relief and adequate pass of
      contrast to proximal ureter were observed in the remaining case, although
      pyelocalicilar dilation was not improved. Three vessels adjacent to the UPJ
      (16.6%) were discovered through the performed pyelotomy incision. Operative times
      were lower than 2 hours. Blood losses were minimal and patient recovery
      uneventful allowing hospital discharges within 48 hours. CONCLUSIONS: To use 3 mm
      laparoscopic scissors allows to perform endopyelotomy without changing
      endoscopes, precisely cutting due to retroperitoneum visualisation, and offers
      the chance to coagulate small calibre vascular elements and to avoid those of
      bigger size.

PMID- 12224168
TI  - [Retroperitoneal endoscopic nephrectomy].
AB  - OBJECTIVES: Nephrectomy is probably the most widely accepted procedure for the
      application of laparoscopic techniques in urology. The great advantages of
      laparoscopy over conventional approaches have justified its indication for
      different renal extirpative procedures: atrophy, renal carcinoma, transitional
      cell carcinoma, polycystic kidney disease, living kidney donation for
      transplantation and partial nephrectomies. The objective of this article is to
      describe the techniques and advantages of laparoscopic nephrectomy through a
      retroperitoneoscopic approach, demonstrating that it is an effective option for
      the majority of cases in which extraction of the kidney is required. METHODS:
      Between January 1991 and January 2001 107 patients with different renal
      conditions were treated at the Instituto Docente de Urologia (IDU) using
      transperitoneal (36 patients) or retroperitoneal (71 patients) laparoscopic
      access. Indications for laparoscopic approach included atrophy, living donation,
      renal carcinoma, urothelial tumour, polycystic kidney disease and partial
      nephrectomy. RESULTS: Nephrectomy trough a transperitoneal approach was completed
      in 33 (91.6%) of 36 patients, being necessary to convert to conventional surgery
      in the remaining 3 cases (8.3%). Retroperitoneoscopic approach was successful in
      all cases (100%). CONCLUSIONS: The retroperitoneoscopic approach is a simple
      procedure that allows its implementation in the majority of patients in which
      there is an indication for nephrectomy. Retroperitoneoscopy provides a rapid
      recovery, minimal analgesic needs, and a short hospital stay. Finally,
      retroperitoneoscopic approach represents a logical evolution for conventional
      flank incisions, providing familiarity with surgical field landmarks and
      management to those urologists that incorporate this new technical modality.

PMID- 12224169
TI  - Laparoscopic donor nephrectomy: why not?
AB  - OBJECTIVES: Laparoscopic donor nephrectomy has undergone explosive worldwide
      growth as the method of choice for removal of living donor kidneys. However, the
      method does have some distinct disadvantages as well. The objective is to define
      real and potential difficulties with the generalized uncritical acceptance of
      this surgical technique. METHODS: The literature and personal experience at the
      largest laparoscopic donor program were reviewed and consolidated. Critical areas
      of technique and management were analyzed. RESULTS: Laparoscopic living donor
      nephrectomy has increased the pool of willing potential renal donors. In
      experienced has the recipient renal function results are equivalent to open
      nephrectomy. CONCLUSIONS: There are risks in performing the operation to the
      donor and to the allograft. These risks are potentially catastrophic and mitigate
      against any casual attitudes about embarking on a laparoscopic donor nephrectomy
      program.

PMID- 12224170
TI  - Laparoscopic cystectomy: indications and limitations.
AB  - OBJECTIVES: To describe the technique and preliminary results of the laparoscopic
      cystectomy as well as to review current indications and limitations of a nouvel
      surgical approach for a classical operation. METHODS: A careful description of
      the key points of the technique of laparoscopic cystectomy and creation of an
      ileal conduit is provided. Operative and immediate complications of this
      operation in a preliminary series of 11 patients are described. RESULTS:
      Laparoscopic cystectomy is proven feasible with a mean operative time of 7.3
      hours and minimal blood loss (median 330 cc.). Transfusion was required in two
      patients and the rate of major complications is in this series for 18%. Minor
      complications account for 27% of the series. Mean hospital stay was 7 days.
      CONCLUSIONS: Laparoscopic cystectomy can be performed safely although a high
      level os skill is needed. The precise role of the technique has yet to be
      described and for the moment being, and till oncological results will be
      confirmed remains under evaluation.

PMID- 12224171
TI  - Complications of laparoscopic urological surgery.
AB  - OBJECTIVES: To describe the complications of laparoscopic surgery in general but
      also specifically in the field of Urology and then analyze the preventive
      measures that must be taken in order to minimize these complications. METHODS: At
      first we outline the absolute and the relative contraindications of laparoscopic
      surgery in general. Then we describe the various intra and postoperative
      complications seen in laparoscopic surgery and finally we discuss the
      complications reported specifically in Urological laparoscopic procedures.
      RESULTS AND CONCLUSIONS: The applications of laparoscopic surgery in Urology
      grows every day. The main complications are vascular injuries and visceral
      lesions but the complications rate diminishes as surgeons improve in their
      learning curve. Laparoscopy for Urology is here to stay.

PMID- 12224173
TI  - [Laparoscopic adrenalectomy].
AB  - OBJECTIVES: To review indications, techniques and results of laparoscopic
      adrenalectomy. METHODS: We retrospectively review our experience with 8 cases of
      transperitoneal laparoscopic adrenalectomy (2 pheochromocytomas, 4 aldosteromas,
      1 myelolipoma and 1 non functioning adenoma). RESULTS: Mean operative time was
      about 3 hours, with an mean estimated blood loss of 200 cc. Mean Hospital stay
      was 2.5 days, complication rate was 10%, being conversion to open surgery between
      5 and 10%. CONCLUSIONS: Laparoscopic adrenalectomy is the operation of choice for
      functioning adrenal tumours and for incidentally diagnosed tumours < or = 6 cm
      that have increased in size in successive radiographic examinations.

PMID- 12224172
TI  - [Laparoscopy in pediatric urology].
AB  - OBJECTIVES: To establish urological pathologies in which video-assisted
      laparoscopy would be indicated as an alternative to conventional surgery.
      METHODS: From 1995 to December 2000 we performed 106 urological laparoscopic
      procedures in 99 children six months to 16 years old (mean age of 7 years). The
      indications for laparoscopy were: a) Diagnostic indications in 60 patients (n)/65
      procedures (p) including intrabdominal testis (n = 28, p = 33) and renal biopsy
      (n = 32, p = 32); b) Therapeutical indications in 33 patients (n)/34 procedures
      (p) consisted of varicocelectomy (n = 5, p = 7), orchiectomy (n = 1, p = 1),
      closure of patent processus vaginalis (n = 2, p = 4), retroperitoneoscopic
      nephrectomy (n = 16, p = 18), renal cyst excision (n = 2, p = 2),
      marsupialization of symptomatic giant lymphocele after renal transplantation (n =
      2, p = 4), and c) Retroperitoneoscopic approach before open access in 6
      patients/7 procedures. RESULTS: The laparoscopic approach was effective in 100%
      and 94.2% of diagnostic and therapeutic procedures, respectively. Conversion to
      an open approach was required in two procedures because of peritoneal perforation
      during retroperitoneoscopic nephrectomy in one case and bleeding after
      retroperineoscopic renal biopsy in the other. Previous retroperitoneal surgery is
      not a contraindication for retroperitoneoscopy. There were no postoperative
      complications with intraoperative morbidity of 2.8%. Overall average hospital
      stay was 1.4 days. CONCLUSIONS: Minimally invasive surgery plays an important
      role in management of pediatric urology patients. Nowadays, there are procedures
      in pediatric urology that can be considered established indications for
      laparoscopic or retroperitoneoscopic approaches.

PMID- 12224174
TI  - Hand-assisted laparoscopic renal surgery: current trends and applications.
AB  - OBJECTIVE: Hand-assisted laparoscopic surgery has recently been introduced in
      order to help ease the learning process associated with standard laparoscopic
      surgery. It has various urological applications in the management of malignant
      and benign disease of the kidney. The purpose of this study is to review the
      applications and the success rate associated with hand-assisted laparoscopic
      surgery. METHODS: A comprehensive literature review of hand-assisted urological
      surgery was performed using MEDLINE search. RESULTS: Hand-assisted laparoscopic
      nephrectomy has been performed for benign and malignant disease, donor renal
      transplant, and nephron sparing surgery with good success. Patients who undergo
      the hand-assisted procedure seem to have less perioperative morbidity than those
      who undergo an open procedure. This approach minimized the warm-ischemia time in
      renal transplantation. CONCLUSION: Hand-assisted nephrectomy is a useful tool
      facilitating the learning process in laparoscopy.

PMID- 12224175
TI  - A brief update on chemokines, chemokine receptors, and HIV.

PMID- 12224176
TI  - HDL, alcohol, and health: from the benefits of moderation to the hazards of
      abuse.

PMID- 12224177
TI  - A case study in hepatitis C disease progression: reaching out while searching for
      new clues.

PMID- 12224178
TI  - The early detection of heavy alcohol consumption using routine clinical
      laboratory test results.

PMID- 12224179
TI  - An assessment of recent improvements in D-dimer testing.

PMID- 12224180
TI  - A stable substrate for DNA microarrays.

PMID- 12224181
TI  - Focus on microscopy. Koehler illumination: an age-old technique impacts modern
      digital imaging.

PMID- 12224182
TI  - The management and prevention of rigid cervical collar complications.
AB  - The rigid cervical collar has been a great addition to the successful management
      of cervical spine injuries. But the collar has been known to offer a false sense
      of security in terms of totally preventing additional and further spinal cord
      compromise and damage. Also, with increased length of collar wear, there is
      development of skin pressure points and ulcer formation, possible delay in
      weaning from a ventilator, potential for exposure to transmission of blood-borne
      diseases. Photographs are used to demonstrate examples of related skin breakdown,
      show proper collar fit, present the result of ineffective cervical
      immobilization, and show how to stabilize the head and neck during a collar
      change. These problem areas are addressed with the dos and don'ts for nursing
      management.

PMID- 12224183
TI  - Health concerns of men with osteoarthritis of the knee.
AB  - PURPOSE: The purpose of this study was to determine health concerns of men with
      osteoarthritis (OA) of the knee for use in the design of appropriate nursing
      interventions. DESIGN/SAMPLE: A one-group, descriptive design was used with a
      convenience sample of 104 men with a clinical diagnosis of OA of the knee.
      METHODS: All participants were recruited from a VA hospital/clinic located in
      Missouri. They were surveyed using the Arthritis Impact Measurement Scales 2
      (AIMS2). FINDINGS: The men in this sample were most concerned about pain, walking
      and bending, and mobility. They rated their present health as fair to good, but
      in 10 years they predicted their health would be worse and their arthritis would
      be a major problem. CONCLUSIONS: Based on these findings, interventions for men
      with OA should focus on strategies to deal with pain and decreased mobility and
      on fostering hope for the future.

PMID- 12224184
TI  - Pathogenesis of anterior cruciate ligament injury.
AB  - Pathology, part of the basic science of medicine and nursing, is an understanding
      of how cellular mechanisms and organ systems function conjointly in the physical
      body. An awareness of the biomechanics and pathophysiology related to a
      particular mechanism of injury (MOI) provides a more appreciative sense of how
      tissues become damaged. Cognizance of the variables and risk factors involved in
      MOI specific to anatomic structures not only helps the Health Care Provider (HCP)
      decide which treatment options are necessary, but knowing risk factors helps in
      preventive tactics, counseling an athlete for optimal training, and
      rehabilitation of the injured athlete. This article discusses the pathophysiology
      related to anterior cruciate ligament (ACL) injury, one of the most common and
      costly ligamentous knee injuries. The differentiation between contact versus
      noncontact mechanisms and risk factors plaguing women athletes will be listed.

PMID- 12224185
TI  - Returning to school: an alternative to 'traditional' education.
AB  - To remain current within the changing health care system, health care
      professionals must continuously develop and sharpen skills to provide effective
      care. Advancement within the profession may be dependent upon the attainment of
      additional degrees. "Traditional" education methodologies do not fit easily into
      busy schedules. Many nurses are finding that distance learning programs provide a
      practical alternative for degree completion. This article presents a basic
      introduction to distance learning. Specific strategies and resources for finding
      appropriate distance learning programs are discussed in detail.

PMID- 12224186
TI  - Neurovascular assessment.
AB  - The outcome of an injured extremity is affected primarily by initial assessment
      and immediate treatment of the extremity. Delaying the recognition of
      neurovascular compromise can cause the amputation of an extremity, or even the
      death of the patient. However, having the foundation of knowledge regarding total
      neurovascular function can equip the nurse with accurate assessment skills and
      the knowledge of the need for immediate action. This essential orthopaedic
      knowledge is used daily by the orthopaedic nurse to provide the best patient care
      possible with the best possible outcome.

PMID- 12224187
TI  - Exercise and older adults: changing behavior with the transtheoretical model.
AB  - The loss of muscle strength, decreased flexibility and range of motion, and
      decreased sense of balance that frequently accompany aging contribute to falls
      and functional decline. Even in advanced old age, one can improve strength,
      decrease the risk of falls, improve cardiorespiratory fitness, and improve
      ability to live independently. The Transtheoretical Model (TTM) of behavior
      change is an internationally recognized model that holds much promise for health
      behavior changes of all types. This article outlines the effects of exercise on
      age-related changes in the musculoskeletal system and describes the TTM as a
      model useful to help older adults change their exercise behavior. Research
      studies are documented that support the effectiveness of the TTM in changing
      behavior. Application of the model is described with specific examples
      illustrated in two case studies.

PMID- 12224188
TI  - When hearing becomes part of healing.
AB  - Noise-induced hearing loss (NIHL) affects 10 million Americans. The number of
      affected people is expected to increase as hearing loss is experienced by younger
      people and life expectancy expands. The problem of noise-induced hearing loss is
      very common among younger as well as older members of the orthopaedic population.
      These patients are at risk for experiencing difficulties in communication with
      care providers as well as family members. However, the nurse is in a strategic
      position to provide care that enhances communication and minimize problems
      associated with hearing loss. This article outlines several nursing interventions
      for caring for a patient with NIHL.

PMID- 12224190
TI  - Diabetes prevention program: education is vital.

PMID- 12224189
TI  - When there are limits on health care resources.
AB  - Controlling health care costs has been a goal within the health care system for
      nearly 40 years. Yet, what is occurring is that health care costs are actually
      increasing, and the quality of care is decreasing. Patients and health
      professionals are complaining that accessibility to services is limited. There
      are inadequate numbers of nursing staff to care for patients who are both sicker
      and have shorter lengths of stay. Patients are bewildered by a system that they
      find to be extremely impersonal and difficult to navigate. This article uses a
      hypothetical case to identify and examine some of the ethical issues related to
      access to health care within a managed care system. Recommendations for nurses
      are presented to help them meet the challenges of limited health care resources.

PMID- 12224191
TI  - The visually impaired specialty diabetes educator: seeing is believing.

PMID- 12224192
TI  - Using the nondiet approach to diabetes meal planning.
AB  - Diabetes educators can present the best alternatives for individuals to achieve
      their health goals. We need to be open to less structure when the situation
      allows or when it is necessary to do so. By opening our minds to new
      possibilities, we can help patients create the best scenario for their lives to
      be as normal as possible while achieving glycemic control.

PMID- 12224193
TI  - Using social marketing to develop diabetes self-management education
      interventions.

PMID- 12224194
TI  - The diabetes educator as an entrepreneur: starting your business.
AB  - If you determine that you have many of the attributes of an entrepreneur
      (including being a risk taker), if you have a passion for your products and
      services, and if you are willing to risk an uncertain income, then you are ready
      to be an entrepreneur. The steps outlined in this article provide a basic
      overview of how to set up a business. If you decide to become an entrepreneur,
      there are numerous books and Web sites to guide you through the steps of
      establishing and managing a business. Although the challenges of becoming an
      entrepreneur may seem intimidating, becoming an entrepreneur can be very
      rewarding.

PMID- 12224196
TI  - Put into practice. Diabetes care processes and outcomes in patients treated by
      nurse practitioners or physicians.

PMID- 12224195
TI  - Expanding the team: the use of volunteers in a diabetes education program.

PMID- 12224197
TI  - Feasibility of a health promotion intervention for a group of predominantly
      African American women with type 2 diabetes.
AB  - PURPOSE: This feasibility study was undertaken to determine if a group of
      predominantly low-income, low-education, African American women with type 2
      diabetes could achieve good compliance and improved health outcomes with a
      carefully structured health promotion intervention. METHODS: The sample consisted
      of 30 participants from an urban setting who were diagnosed with type 2 diabetes
      but also had multiple chronic conditions (e.g., obesity, hypertension, joint
      pain, and depression). Participants attended a university-based health promotion
      program where they completed a 12-week intervention that addressed diet,
      nutrition, and health behavior. Transportation was provided at no cost to the
      participants. RESULTS: Compliance with the 12-week program was 72.5%.
      Participants made significant improvements in total cholesterol and LDL
      cholesterol levels, cardiovascular fitness, muscular strength and endurance, and
      nutrition knowledge. CONCLUSIONS: African American women with type 2 diabetes
      residing in difficult living environments (i.e., poverty, high crime, and lack of
      family support) can achieve good compliance and health outcomes with a structured
      health promotion program provided that barriers to participation (e.g.,
      transportation, cost, and commitment) are removed prior to and during the
      intervention.

PMID- 12224198
TI  - An initiative to improve diabetes care standards in healthcare organizations
      serving minorities.
AB  - PURPOSE: This study was designed to assess changes of diabetes care standards in
      healthcare organizations that participated in 2-year initiative to improve
      diabetes care and expand outreach in minority communities. METHODS: An
      independent sample of the medical records of adults with type 2 diabetes was
      randomly drawn at 3 points of time (N = 829). Rates of compliance with 20
      selected measures of standards of basic diabetes care were measured and compared
      over time. RESULTS: Significant improvements in compliance rates from baseline to
      the end point were found in 11 measures including annual hemoglobin A1C testing
      (65.8% to 76.3%), annual lipid profile (33.8% to 49.1%), and biannual lower
      extremity examination (40.0% to 56.3%). CONCLUSIONS: Improvements in diabetes
      care were credited with giving providers feedback on their compliance and
      increasing support of patient self-care, especially through tailoring outreach
      and services to minorities.

PMID- 12224200
TI  - Protocol for outpatient screening and initiation of continuous subcutaneous
      insulin infusion therapy: impact on cost and quality.
AB  - PURPOSE: The purpose of this study was to determine the effectiveness of a
      screening protocol in identifying subjects who would initiate continuous
      subcutaneous insulin infusion (CSII) and continue the therapy for at least 2 1/2
      years. METHODS: One hundred four subjects were recruited to participate in a
      screening protocol involving a mock trial of insulin pump use. Participants who
      initiated CSII were followed for 2 1/2 years; those deemed ill suited for CSII
      used multiple insulin injections. Discontinuation rates, quality of life, and
      costs were evaluated for subjects using CSII. Baseline and quarterly hemoglobin
      A1C (A1C) were measured and compared. RESULTS: The screening protocol identified
      37 subjects (35.6%) who were unsuited for CSII. Subjects who initiated CSII
      reported enhanced quality of life and exhibited a low discontinuation rate
      (3.3%). No safety issues were encountered. Screening, CSII initiation, and follow
      up were accomplished at lower costs per subject ($2431.50) than those reported in
      the Diabetes Control and Complications Trial (DCCT) ($8265.00). A1C was
      significantly lower over time for subjects receiving CSII compared with those
      receiving multiple injections. CONCLUSIONS: A structured screening protocol with
      trial pump use was effective in identifying individuals who would initiate CSII
      and continue the therapy for at least 2 1/2 years.

PMID- 12224201
TI  - [Rehabilitative nursing of brain injured patients].

PMID- 12224199
TI  - Diabetes care processes and outcomes in patients treated by nurse practitioners
      or physicians.
AB  - PURPOSE: The purpose of this study was to compare selected diabetes care
      processes and outcomes of nurse practitioners (NPs) and physicians (MDs) in the
      primary care of adults with type 2 diabetes. METHODS: Adults with type 2 diabetes
      and no regular source of primary care were enrolled from the emergency room and
      randomized to an NP or MD practice. Chart reviews were conducted to assess
      processes of care; patient interviews and hemoglobin A1C (A1C) testing were
      performed to measure patient outcomes. RESULTS: NPs were more likely than MDs to
      document provision of general diabetes education and education about nutrition,
      weight, exercise, and medications. They were more likely to document patient
      height, urinalyses results, and A1C values. No differences were found in
      documenting current medications; alcohol, illicit drug, or tobacco use;
      depression; weight and blood pressure; foot and cardiovascular exams; blood
      glucose and creatinine testing; or referral to ophthalmologists. No differences
      were found in patient outcomes. CONCLUSIONS: This study provides preliminary
      evidence of interdisciplinary differences in the processes of care employed by
      primary care NPs and MDs in caring for patients with type 2 diabetes. NPs
      documented the provision of diabetes education and selected monitoring tests more
      frequently than MDs; however, these differences were not reflected in 6-month
      patient outcomes.

PMID- 12224202
TI  - [Better quality of life for child and parents].

PMID- 12224203
TI  - [As important as nursing itself].

PMID- 12224204
TI  - [Nursing care specialist replaces the clinical nurse].

PMID- 12224205
TI  - [The bathing ritual].

PMID- 12224206
TI  - [Becoming real!].

PMID- 12224207
TI  - ["The black shadow always follows us"].

PMID- 12224208
TI  - ["Fleeing the companion of good and bad days"].

PMID- 12224209
TI  - [Key point: transmitting information].

PMID- 12224210
TI  - [Quality assessment provides new self confidence].

PMID- 12224211
TI  - [To be at the elevation of the terminal child].

PMID- 12224212
TI  - [A segment of palliative care is put in place].

PMID- 12224213
TI  - [Primary nursing achieves a new work profile].

PMID- 12224217
TI  - Deadly transplants.

PMID- 12224218
TI  - Don't ignore heart-attack blues.

PMID- 12224219
TI  - The faces of Alzheimer's.

PMID- 12224221
TI  - Beyond the horizon.

PMID- 12224220
TI  - The state of the planet.

PMID- 12224222
TI  - Let them run wild.

PMID- 12224223
TI  - New war on waste.

PMID- 12224224
TI  - The winds of change.

PMID- 12224226
TI  - A strong climate plan.

PMID- 12224225
TI  - Mean clean machines.

PMID- 12224227
TI  - Bush takes a backseat.

PMID- 12224228
TI  - Lessons from lost worlds.

PMID- 12224229
TI  - The young can't wait.

PMID- 12224230
TI  - Too green for their own good?

PMID- 12224231
TI  - The challenges we face.

PMID- 12224232
TI  - The power of one.

PMID- 12224233
TI  - Managing head injuries.
AB  - The patient who presents with a serious head injury is often very difficult to
      manage. The airways is of primary concern; adequate ventilation must be provided
      and aspiration protected against. Recent studies suggest that hyperventilation
      may be as beneficial as was earlier believed. As the pCO2 level decreases,
      vasoconstriction occurs. If the level falls too low, cerebral perfusion is
      restricted, and profound cerebral anoxia may ensue. Current standards call for a
      ventilatory rate to allow for moderate respiratory alkalosis, in theory to mildly
      constrict teh vessels but still provide adequate perfusion. Arterial blood gas
      analysis in the ED is the definitive measurement of airway management in the
      field. Remember that the anatomy of the meningeal layers places the arteries
      primarily in the epidural space and the veins in the subdural space. A bleed in
      the epidural space often presents with a rapid onset of signs and symptoms, as
      was obvious in this traumatized patient. When a bleed occurs in the subdural
      space, the onset is usually more insidious, and an accurate history is a key to
      field diagnosis. As the hemorrhage expands, compression displaces the brain
      within the cranial vault. This displacement causes pressure to be exerted on the
      medulla of the brainstem. Cushing's Traid is a result of this pressure on the
      medulla and is evidence by the pulse slowing while systolic blood pressure rises
      and respirations become ataxic. Vomiting is often associated, and as the bleed
      continues, herniation syndrome begins. Decorticate posturing is displayed,
      followed by decerebrate posturing if relief is not provided. It is important to
      distinguish between decorticate and decerebrate posturing. It is important to
      distinguish between decorticate and decerebrate posturing. An easy way to
      remember the differences is to picture the anatomy of the brain. The cerebral
      cortex lies above the cerebellum, so when a patient's arms flexed up toward the
      face , he is pointing to his "core" (de-cor-ticate). As the arms extend downward,
      he is pointing to his cerebellum(de-cere-brate). T o manage the head-injured
      patient, it is imperative to anticipate potential developments, as well as
      protect against underlying injuries that may not be fully evaluated until arrival
      at the ED. Cervical spine often accompany head injuries, and full spinal
      immobilization is a mandatory precaution in all presentations. With the expanding
      hematoma found on this patient's neck, vascular damage ws obvious and contributed
      to the suspicion of spinal injury. As the intracranial pressure rise, vomiting
      and seizures are common. Placement of an endotracheal tube and having suction
      equipment ready are the best tools to prevent against aspiration. It is possible
      to angle the long spine board 10-15 degrees, exercising caution to ensure the
      patient's spinal alignment is not manipulated during the process. Seizures are
      usually treated with anticonvulsants like Valium. When a seizure accompanies a
      head injury, it is a direct result of the increased intracranial pressure and has
      a generally poor response to Valium, as the underlying cause of the seizure still
      exists. In this case, the patient had a full neuromuscular blockade, and any
      seizure would not have been recognized as long as the paralytics were on board.
      Early notification to the ED is essential, reporting all findings and
      interventions. This can alert them and give them the opportunity to prepare
      specialized equipment, such as CT scanners, mechanical ventilators, etc. Also,
      consider transportation options and the length of time to definitive care,
      including neurosurgical evaluation. This patient needs to be seen in a trauma
      center capable of the most thorough evaluation and management. Evacuation by air
      ambulance may be the most appropriate method of transport.

PMID- 12224234
TI  - EMS response to wildland fires.
AB  - Wildland fires are unpredictable and dangerous. Be prepared by responding to
      wildland fires with the appropriate level of training and wearing appropriate
      gear. Remain aware of the fire's behavior and weather, fuels and topography.
      Anticipate the fire's actions and how they will affect your health and safety.
      Establish preplanned escape routes and safety zones. Your safety and survival
      while providing care at or near the fire line may depend upon proper planning,
      training and equipment.

PMID- 12224235
TI  - "All-out response". EMS in Israel.

PMID- 12224236
TI  - Terror in September.

PMID- 12224237
TI  - The electronic revolution. Report writing in the 21st century.

PMID- 12224238
TI  - The medical communications officer. A resource for data collection, quality
      management and medical control.
AB  - Pinellas County EMS' Medical Communications Officers provide a wide variety of
      services to patients, field clinicians, managers and their medical director. The
      concurrent data collection processes used in the MCO program for performance
      measurement of resuscitation efforts, intubations, submersion incidents and
      aeromedical transports for trauma cases have been very effective in the
      integration of data from multiple computer databases and telephone follow-ups
      with field crews and receiving emergency department staffs. This has facilitated
      significant improvements in the performance of these and many other aspects of
      our EMS system.

PMID- 12224239
TI  - It's all in the palm of your hand. Part 1: What is a palm pilot?

PMID- 12224240
TI  - Tapping the potential of paging.

PMID- 12224241
TI  - A is for airway: digital and nasal endotracheal intubation.

PMID- 12224242
TI  - How does your garden grow? Herbal remedies EMS may encounter.
AB  - Millions of dollars are spent annually on over-the-counter herbal remedies. While
      most of these self-administered cures are benign, some may pose a problem for EMS
      professionals, either through inherent adverse effects or interactions with
      prescription medications. This article has highlighted several of the more
      popular herbal remedies and given brief information about the typical problems
      that EMTs and paramedics may encounter in the field.

PMID- 12224243
TI  - [Non-invasive estimation of the temperature gradient of internal living tissue
      layers by ultrasound method].
AB  - The paper deals with the designing of equipment for telecontrol of changes in the
      temperature of the internal layers of objects, which cannot be measured by
      contact methods. The bases for this are an analysis of the ultrasound
      oscillations reflected from the internal heterogeneities of the environment, as
      well as restoration of the pattern of a pressure propagation velocity along the
      sounding beam. The feasibility of telecontrol of temperature is analyzed by using
      the boundary integrated equations. A procedure is proposed on the basis of the
      difference-phase method for estimating the velocity of propagation of reflected
      signals. Requirements for the equipment and algorithms for processing the signals
      observed are formulated. Ways for further studies are directed.

PMID- 12224244
TI  - [Adaptive methods in the electric impedance reconstruction of biologic objects].
AB  - The algorithms of processing data array for electric impedance tomography are
      proposed. The ways of developing medical diagnostic complexes that involve
      electric impedance diagnosis and electric stimulation in a patient are shown. The
      adaptive chains of coordination of impedances have been studied on mathematical
      models and in experiments. These chains make it possible to fix high-frequency
      power during electrostimulation and to measure the complex impedance of objects.

PMID- 12224245
TI  - [Analysis of dosage loads on patients and personnel in the use of "FSTs-U-01" x
      ray image-enhanced fluorography].
AB  - The paper considers the specific features of formation of dosage loads during
      studies on a digital fluorograph with movable X-ray image amplifier. It is
      concluded that smaller weekly dosage loads should be used for this type of
      fluorographs than those described in relevant normative documents.

PMID- 12224246
TI  - [Computer medical monitors: state-of-the art and perspectives].
AB  - The paper shows that the currently available Russian and foreign computer medical
      monitors (CMMs) may generally solve the simplest tasks of data visualization,
      recording, and archiving. It is justified that to enhance the "intellectuality"
      of CMMs, it is necessary to turn to the solution of the problems and tasks of
      medical monitoring, by using the whole range of methods for biosignal detection
      and processing, which has been accumulated in modern radio engineering, in the
      theory of communication, and in engineering and medical cybernetics.

PMID- 12224247
TI  - ["Public Health-2001" exhibition: medical equipment].
AB  - The paper presents a review of medical equipment displayed at the 11th
      International Exhibition "Public Health, Medical Equipment, and Drugs" ("Public
      Health-2001"). The exhibition was held in Moscow on December 3-7, 2001.

PMID- 12224248
TI  - ["Public Health-2001" exhibition: medical devices and apparatus].
AB  - The paper presents a review of medical devices and apparatuses displayed at the
      11th International Exhibition "Public Health, Medical Equipment, and Drugs"
      ("Public Health-2001") in Moscow on December 3-7, 2001.

PMID- 12224249
TI  - [Correction of light refraction and reflection in medical transmission optical
      tomography].
AB  - The effects of light refraction and reflection on the quality of image
      reconstruction in medical transmission optical tomography of high-scattering
      media are considered. It has been first noted that light refraction not only
      distorts the geometric scheme of measurements, but may lead to the appearance of
      object areas that cannot be scanned. Some ways of decreasing the effect of
      refraction on the reconstruction of spatial distribution of the extinction
      coefficient are stated.

PMID- 12224250
TI  - [Non-invasive blood pressure measuring device].
AB  - Algorithms have been developed for the Russian non-invasive blood pressure
      measuring monitor MPK-01 that applies a frequency excess pressure transducer. The
      monitor uses oscillometry. A preliminary estimate of the accuracy of blood
      pressure measurement for its conformity to the ANSI/AAMI (USA) and BHS (UK)
      standards has indicated the legitimacy of the algorithm proposed for processing
      if there are hardware restrictions inherent in this monitor.

PMID- 12224251
TI  - [Module for analyzing physiological processes of the OMIS software complex].
AB  - The informational technology designed for systems analysis of changes in the
      characteristics of single variations in physiological process is outlined. This
      technology has been used in the module of analysis of the physiological processes
      of an software complex.

PMID- 12224252
TI  - [Laser angioplasty technology].
AB  - The authors propose a laser angioplasty technology that differs in that pulse
      periodic nitric N2-laser (wavelength, approximately 337 nm; power, 0.5 W; pulse
      energy, 5 mJ; repetition frequency, approximately 100 Hz) is used as a source of
      laser radiation. The technology has an environmental purity (a working nitrogen
      helium mixture) and a vast resource (approximately 10(7) pulses). A conical
      profile quartz fiber (focon) that can accumulate and transmit the bulk of laser
      energy is employed to transmit laser light.

PMID- 12224253
TI  - [A unit for testing semiautomatic and automatic tools to measure blood pressure
      and heart rate].
AB  - To test automatic and semiautomatic tools for measuring blood pressure and heart
      rate, the authors propose an automatic device that generates cuff pressure and
      compares it with reference pressure. Based on this comparison, an error of blood
      pressure measurement is calculated. Similarly, that of heart rate measurement is
      defined.

PMID- 12224254
TI  - [OS-250-01 illumination for endoscopic apparatus].
AB  - The paper gives information on the new illuminator for endoscopic apparatuses,
      which provides higher light optic and electric characteristics than do its
      existing analogues. It also presents the specific features of the illuminator and
      compares the technical data of the new illuminator and its analogues.

PMID- 12224255
TI  - [New non-invasive Doppler ultrasound study of blood flow in segmental arteries].
AB  - The authors have proposed and tested a new noninvasive technique of Doppler
      ultrasound study of impaired blood flow in the segmental arteries, which
      indirectly evaluates spinal cord hemodynamics in vertebral column diseases.
      Clinical trials of the technique proposed have provided evidence for the
      association of blood flow in the segmental arteries with the degree of vertebral
      column canal and kyphotic deformities. A combined impact of spinal deformity and
      impaired blood flow in the segmental arteries at the level of lesion on the
      severity of neurological disorders and on deterioration of life quality in
      patients with spinal inflammatory diseases has been found. A relation of impaired
      arterial blood flow of the lower extremity to circulatory changes in the
      segmental arteries has been established in spinal diseases.

PMID- 12224256
TI  - [Biochemical characteristics of hepatic functions in different clinical forms of
      chronic opisthorchiasis].
AB  - The main biochemical indices of hepatic functions (the activities of alanine
      aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase,
      alkaline phosphatase, alpha-amylase, choline esterase and the concentrations of
      total bilirubin, cholesterol, and glucose) were studied in the sera of 256
      patients with chronic opisthorchiasis. It was found that with diseases manifested
      in different clinical forms (cholangitis, cholecystitis, cholangiocholecystitis,
      cholangiohepatitis, cholecystitis in combination with pancreatitis), most study
      indices are within the normal ranges, but significantly differ from the means in
      a group of apparently healthy individuals. The findings suggest that such
      clinical forms of opisthorchiais as cholangiocholecystitis and cholangiohepatitis
      are characterized by manifestations of cytolysis and cholestasis, as
      cholecystitis is manifested by cytolysis, as cholecystitis in combination with
      pancreatitis, by cholestasis, and as cholangitis, by cholestasis and hepatic cell
      insufficiency. It is possible that further studies will provide evidence for how
      to correct detected disorders during pathogenetic therapy.

PMID- 12224257
TI  - [The populational structure of peripheral lymphocytes in patients in the acute
      phase of opisthorchiasis].
AB  - The lymphocytic populations of the immune system were studied in patients
      diagnosed as having acute opisthorchiasis before and 1-3 days after treatment
      with biltricide in a dose of 60 mg/kg body weight. The acute phase of
      opisthorchiasis is characterized by the activation of B lymphocytes and
      immunological cellular reserve, by depressed T-lymphocytic population with a
      decreased helper inductor and suppressive killer potential. Three days after
      dehelminthization, there was a trend for immunoregulatory T cells to become
      normal. The high levels of B lymphocytes and zero cells were preserved.

PMID- 12224258
TI  - [Adaptability of Opisthorchis felineus metacercariae as a result of altered
      phagocytic activity of polymorphonuclear neutrophils].
AB  - The higher absorptivity of neutrophils during their alpha-tocopherol stimulation
      has been found to promote lower adaptability in the metacercariae of Opisthorchis
      felineus, a reverse picture was observed when cyclophosphanum was used. The
      antihelminthic effect of biltricide is probably to be unassociated with the
      changed functional activity of polymorphonuclear leukocytes, but to be determined
      by its direct action on helminths. This phenomenon was studied on golden hamsters
      inoculated with Opisthorchis felineus. On day 2 after inoculation, the following
      drugs were given for a fortnight: biltricide in a single dose of 60 mg/kg weight;
      biltricide used in a daily fractionated dose of 60 mg/kg; cyclophosphanum (6
      mg/kg, every second day); alpha-tocopherol in a daily dose of 30 mg every day.

PMID- 12224259
TI  - [Serological assay in the assessment of the trichinosis epidemiological situation
      in the Tiumen' region].
AB  - A total of 3022 sera from patients with suspected trichinosis and healthy
      individuals were studied by enzyme immunoassay using the commercial test systems
      of the Ye.I. Martsinovsky Institute of Medical Parasitology and Tropical Medicine
      (Moscow) and of the private joint stock company "Vector-Best" (Novosibirsk). The
      study indicated the trichinosis situation of strain in all subjects of the
      Russian Federation, including the Tyumen Region. The proportion of positive
      serological assays during diagnostic studies was 15.4%, that of
      seroepidemiological surveys was 3.3%. This poor situation associated with this
      entity is confirmed by group, "familial", and single cases of clinical
      trichinosis associated with ingestion of the meat of brown bears, badgers, and
      dogs and pork. The presence of natural trichinosis foci in the Tyumen Region is
      unquestionable, there is no evidence for formed synanthropic foci. An increase in
      the risk of trichinosis infection in the region is favoured by both
      socioeconomical and environmental epizootological prerequisites associated with
      the factors of technogenic and anthropic pressure on the ecosystem. Growing
      epidemic hazard of trichinosis foci requires that controlling and preventive
      measures shall be included into social development programmes for the districts
      and south of the Tyumen Region.

PMID- 12224260
TI  - [Fish infection with Opisthorchis larvae in Russia and some contiguous countries
      (by the materials of the "Cadaster of opisthorchis infection foci in Russia in
      1994"].
AB  - A cadastre of opisthorchiasis foci with places under study and specious fish
      invasion with larvae of this helminthiasis has been first drawn up. Opisthorchis
      larvae have been found to be recorded in 23 species and 2 subspecies of the
      Cyprinidae family and 1 species of the Cobitidae family. The cadastre permits the
      areas epidemiologically hazardous due to opisthorchiasis to be determined. The
      data on fish species-specific infection in different river basins may render a
      great deal of aid to sanitary-and-epidemiological surveillance workers in
      implementing preventive measures in specific regions.

PMID- 12224261
TI  - [Efficacy of mefloquine, halofantrine, and coarteme in the treatment of tropical
      malaria].

PMID- 12224262
TI  - [Ecdysten in the treatment of giardiasis].
AB  - The drug ecdisten as tablets is the natural compound ecdisteron was extracted
      from Rhaponticum carthamoides (Willd.) Jljin. Ecdisten was tested in the
      treatment of 32 and 3 patients with persistent and acute giardiasis,
      respectively. A ten-day course of ecdisten, 5 mg 3 or 4 times a day, resulted in
      a clinical and parasitological recovery in 22 (68.7%) and 3 patients,
      respectively. After the reuse of a ecdisten course in 4 patients with persistent
      giardiasis wherein its initial dose was increased, recovery was achieved in 3
      cases, the efficacy of the agent was 78.1%. Ecdisten should be used to treat
      giardiasis, in its chronic pattern or resistance to conventional giardicial
      agents.

PMID- 12224263
TI  - [Parasitic diseases are a risk factor of inflammations of the small pelvis
      organs. Trichomoniasis].
AB  - Clinical and laboratory studies were made in 2259 persons by using serological
      assays, including cultural and bacterioscopic assays in 1824 and 363 persons,
      respectively, in order to indicate Trichomonas infection among men, women, and 2
      15-year-old children who had chronic inflammation of the urogenital system, as
      well as among children aged 2 months to 16 years who had a severe somatic
      disease. Parasitic cenoses of the urogenital tract were studied in women with
      trichomoniasis and reproductive dysfunction. Trichomonas invasion is an
      etiological factor of inflammatory small pelvic diseases, chronic prostatitis,
      reproductive dysfunction in males and females. Furthermore, trichomoniasis is an
      essential factor, that predisposes to recurrent viral infections: genital herpes
      and pointed condyloma, and substantially increases the risk of birth of babies
      with clinical manifestations of intrauterine infection. According to the studies,
      a laboratory diagnosis of trichomoniasis should be made by cultural assay due to
      the low sensitivity of bacterioscopy by sampling a biological material from
      females in the periovulatory period that corresponds to the hyperestrogenicity,
      which substantially increases the number of isolated cultures and characterizes
      the depth of integration of metabolic processes of a parasite and its host.

PMID- 12224265
TI  - [Spread of giardiasis in Perm city].

PMID- 12224264
TI  - [Antimicrobial, echinococcidial and immunostimulating properties of the drug
      Cheblin-SK-1].
AB  - The antimicrobial properties of the drug Cheblin-CK-1 (CCK-1) were determined in
      mice intraabdominally inoculated with Proteus mirabilis-4691 in a dose of 140-200
      million daily cultured microbial bodies. Its comparison agent was ampicillin. CCK
      1 was found to act as an antibiotic similar to ampicillin in its effects. The
      antimicrobial activity of CCK-1 against Staphylococcus aureus and Escherichia
      coli isolated from the contents of echinococcal cysts from patients operated on
      was also established. Its echinococcidial activity was found in experiments on
      the cotton rats and piglets inocculated with echinococci. CCK-1 was also tested
      on volunteers. Before surgery, 186 patients with echinococcosis took the drug and
      26 patients with the same disease did not and they served as controls. At first
      the drug suppressed the growth of parasitic larvocysts with destruction and death
      of 85-95% of germinal elements of larvocysts and then killed parasites. In
      patients receiving a complete course of its therapy, protein and amino acid
      metabolisms restored, followed by immunity recovery.

PMID- 12224266
TI  - [Risk of human infection with Ixodes tick-borne relapsing fever in different
      regional subzones of the Perm region].
AB  - Serological and epidemiological surveys covered 2407 persons in 20 populated
      localities situated in all large geographical and regional subdivisions
      (subzones) in the Perm Region. Indirect immunofluorescence tests revealed serum
      immunoglobulins to Borrelia burgdorferi sensu lato. Antibodies in 1:40 or higher
      dilution were found in nearly 5 to 11% of the dwellers of localities in the
      subzones of south taiga, coniferous broad-leaved forests, and forest steppe;
      about 3-7% and 1-6% of them were present in the populations of mountain and
      middle taigas, respectively. According to the frequency of tick suction and the
      proportion of an immune interlayer among the population within the Perm Region,
      four districts were identified by varying risks for infection (epidemic hazard)
      with Ixodes tick-borne relapsing fever. The populations living in the subzones of
      south taiga, coniferous, broad-leaved forests, and forest steppe run the greatest
      risk. An area at average infection risk area corresponds to the south part of a
      mountain taiga subzone and that at lower risk does to the south part of a middle
      taiga subzone. There is no possibility of relapsing fever contamination outside
      the area of Ixodes persulcatus ticks at all. Comparison of their own findings and
      official statistics has made the authors conclude that there is a great
      hyperdiagnosis of relapsing fever in the region in question.

PMID- 12224267
TI  - [A laboratory model of the parasitic system of Lyme disease].
AB  - A laboratory model of the parasitic system of Lyme borreliosis (LB) with Ixodes
      persulcatus and Borrelia burgdorferi s.s. underwent 5 epizootic cycles (Cycle I
      transition of Borreliae by the scheme a tick-->a mouse-->a tick corresponds to
      the seasonal cycle). A group of 5-6 mice was inoculated with the suspension of
      infected nymphs by the intracutaneously route and 35-45 days later intact tick
      larvae or nymphs were fed on them. In the first three cycles, 40-100% of mice in
      a group (a total of 33 of 59) were susceptible, but 3 of 11 groups of mice were
      not inoculated. 20-50% of larvae and 75-92% of nymphs were susceptible on the
      infected mice. The mean geometric abundance of borreliae was 2.8-6.3 cells per
      100 fields of vision in the nymphs infected in the larval phase and 16.1-29.5
      cells in the image phase. In cycle IV, 2 of 6 groups of mice were unsusceptible
      to borreliae and 5 of the 17 mice from 4 groups got infected. One mouse died from
      Lyme borreliosis when larvae were fed on it. The nymphs remolted from underfed
      larvae were infected in 62.2% of cases, the mean geometric abundance in these
      nymphs was 5.7% per 100 fields of vision. A total of 3.2-14.7% of the ticks fed
      on the remaining 4 mice were infected and the abundance of boreliae was 1-2 per
      100 fields of vision. In cycle V, one of 12 mice got infected, the infection rate
      in nymphs was 9.1%, the abundance of borreliae was 1 per 100 fields of vision.
      Thus, as the number of epizootic cycles increases, the proportion of infected
      mice, that of ticks infected on these mice on feeding, and the abundance of
      borreliae in the infected ticks decrease. Moreover, there was a reduction in the
      length of borreliae reduced from 17-18 mm to 10-11 mm and in the duration of
      multiplication and preservation of borreliae in the infected ticks and there was
      concurrently an increase in the duration of development of an infectious process
      in mice. It is suggested that the population of borreliae consists of 2
      morphophysiological groups or more. During cultivation of the laboratory model of
      the parasitic system of Lyme borreliosis, a group of borrelia that are short and
      slightly pathogenic for mice had got many points in its favour. A five-fold
      procedure of artificial election of precisely defining this group set the model
      on the verge of disappearance. The capacity of the populations of borreliae to
      alter their properties rapidly and fundamentally suggests that there might be
      violent annual fluctuations in human morbidity.

PMID- 12224268
TI  - [Ecological factors that influence the dynamics of the total store of Daursk
      suslik fleas in the Transbaikal natural focus of plague].
AB  - Based on 20-year (1967-1987) studies of the dynamic of the total store of the
      imago of Daursk souslik fleas in the Transbaikal natural focus of plague and of
      changes in the abiotic and biotic parameters of the environment, the authors have
      identified factors that statistically significantly influence the study
      processes. The analysis was made by the nonlinear multiple regression test. One
      to three predictors of flea abundance have been detected for each month from May
      to April inclusive.

PMID- 12224269
TI  - [Human parasitizing echinostomatata (Trematoda, Fasciolidae) in mammals in
      Belorussian forest zone].
AB  - Domestic and wild mammals in Byelorussian Polesye have been found to have 3
      species of echinostomatates known as human parasites: Echinochasmus perfoliatus
      (Ratz, 1908), Echinostoma revolutum (Froelich, 1802) and Isthmiophora (=
      Euraryphium) melis (Schrank, 1788). Human beings may be infected on ingestion of
      mollusks, fish, and Amphibia (frogs) invaded with larvae of these helminths.
      Although, cases of human invasion have not been recorded in Byelarus, there is an
      infection risk group, this should be borne in mind by medical workers.

PMID- 12224270
TI  - [A case of severe strongyloidiasis].

PMID- 12224271
TI  - [Cases of toxocara infection on the Sverdlovsk railway].
AB  - The results of serological testing for Toxocara infection in patients who had
      referred for a railway hospital of the Sverdlovsk railway were summarized.
      Positive serological tests were in the titer ranges 1:200 to 1:1600 in 12.8% of
      the examinees, including the titer range 1:800 or more in 8.5%. Brief extracts
      from some case histories are given.

PMID- 12224272
TI  - [Clinical and parasitological diagnosis of human dirofilariasis].
AB  - The paper reports two new cases of human dirofiliriasis (its causative agent is
      Dirofiliria repens) with a rare clinical diagnosis of funiculitis of the right
      scrotal spermatic cord in a 12-year-old boy from the Tambov Region and of
      erysipelatous inflammation of the outer side of the right leg in a 68-year-old
      woman who resides in Moscow and lives in her country house in the Shakhovsky
      District, Moscow Region, in summer. Both cases of invasion are regarded as local.
      The bodies of the D. repens females detected measured 110 x 0.476-0.48 and 135 x
      0.56-0.60 mm, respectively, and the females were identified as impubertal and
      pubertal, but infecund. In the former case, dirofiliriasis was an etiological
      factor of spermatic cord funiculitis. In the latter case, the location of
      Dirofiliria provoked prolonged (7-month) erysipelatous inflammation. Emphasis is
      placed on the implication of dirofiliriasis in human pathology. To have a more
      intimate knowledge of parasitic etiology will help physicians in making a
      differential diagnosis of dirofiliriasis and in elaborating a correct treatment
      policy after a clinical and parasitological diagnosis is established.

PMID- 12224273
TI  - [A case of isolated hepatic cysticercosis in a nine-year-old girl].

PMID- 12224274
TI  - [Affliction of leptospirosis in some professional population groups].

PMID- 12224275
TI  - [Comparative characterization of clinical manifestations of immune deficiency in
      patients with acute and chronic Opisthorchis invasion].

PMID- 12224276
TI  - [Force-dependent effects of interleukin-8 gene expression in endothelial cells
      exposed on fluid shear stress].
AB  - Fluid shear stress plays an important role in many physiological and
      pathophysiological processes of the cardiovascular system. Previous studies have
      identified the exposure of vascular endothelial cells to fluid mechanical forces
      can modulate the expression of many genes, including IL-8 gene expression, and IL
      8 expression induced by fluid shear stress was time-dependent. To investigate the
      role of intensity of fluid shear stress on IL-8 expression in human umbilical
      vein endothelial cells (HUVECs), we had HUVECs exposed to shear stress 2.23,
      4.20, 6.08, 8.19, 9.67, 12.15, 14.40, 16.87, and 19.29 dyne/cm2 respectively and
      employed quantitative reversal transcription-polymerase chain reaction (qRT-PCR)
      to assay the expression of IL-8 mRNA. The results show that IL-8 mRNA did not
      express in HUVECs untreated with fluid shear stress. The IL-8 mRNA expression by
      shear stress was force intensity-dependent. After HUVECs exposed to low fluid
      shear stress (2.23 dyne/cm2) for 1 h or 2 h, IL-8 mRNA expression increased near
      68 or 52 times as that of HUVECs exposed to high fluid shear stress (19.29
      dyne/cm2). The linear regression equations between IL-8 mRNA expression (log
      (copies), y) and shear stress (dyne/cm2, x) are: y = 7.57 - 0.11x, r = 0.97 (for
      1 h); y = 7.92 - 0.10x, r = 0.96 (for 2 h). This in vitro study demonstrates the
      expression of IL-8 gene can be regulated by fluid shear stress. The low shear
      stress could induces much more expression of IL-8 mRNA, which plays probably an
      important role in the pathogenesis of inflammation and arteroatherosclerosis.

PMID- 12224277
TI  - [The effects of surface morphology of calcium phosphate ceramics on apatite
      formation in dynamic SBF].
AB  - Bone-like apatite formation on the surface of calcium phosphate ceramics has been
      believed to be the prerequisite of new bone growth on ceramics and to be related
      to the osteoinductivity of the material. The research of the factors effecting
      bone-like apatite formation is a great help in understanding the mechanism of
      osteoinduction. This paper is aimed to a comparative study of in vitro formation
      of bone-like apatite on the surface of dense and rough calcium phosphate ceramics
      with SBF flowing at different rates. The results showed that the rough surface
      was beneficial to the formation of bone-like apatite, and the apatite formed
      faster in 1.5 SBF than in SBF. Rough surface, namely, larger surface area,
      increased the dissolution of Ca2+ and HPO4(2-) and higher concentration of Ca2+
      and HPO4(2-) ions of SBF and was in turn advantageous to the accumulation of
      Ca2+, HPO4(2-), PO4(3-) near the ceramic surface. Local supersaturating
      concentration of Ca2+, HPO4(2-), PO4(3-) near sample surface was essential to
      nucleation of apatite on the surface of sample.

PMID- 12224278
TI  - [In vivo degradation and tissue compatibility of polyphosphazene blend films].
AB  - The degradation performance and tissue compatibility of polyphosphazene/polyester
      or polyanhydride (PGP/PLGA or PGP/PSTP) blend films were investigated in mice.
      The results showed that the blend degradation rate could be regulated by
      adjusting PLGA or PSTP content in the blends. For example, the weight loss of
      PGP/PLGA (70:30 by wt) film was 68.4% after 55 days, whereas that of PGP/PSTP
      (70:30 by wt) was 88.5% only after 12 days. Also the mechanisms for in vivo
      degradation of blends of PGP/PLGA and PGP/PSTP were hydrolysed enzymatically and
      non-enzymatically, respectively. The tissue compatibility of PGP/PLGA was better
      than that of PGP/PSTP, and an increase of the percentage of PGP in PGP/PSTP
      blends would help improve the tissue compatibility. These findings suggested that
      polyphosphazene blends be potential materials applied in medical field.

PMID- 12224279
TI  - [Effects of external counterpulsation on the pulsatility of blood pressure and
      blood flow in dogs].
AB  - Pulsatile blood flow plays an important role in maintaining normal vascular
      endothelial function. Quantitative measurement of pulsatility of artery blood
      pressure and blood flow in dogs and effects of enhanced external counterpulsation
      (EECP) on the pulsatility were taken in this study. Common carotid artery blood
      pressure and blood flow were measured in 6 beagle dogs that had suffered from an
      acute myocardial infarction 6 weeks before. A 6F tip transducer catheter was
      inserted into the right common carotid artery to measure blood pressure, and
      blood flow was measured in the left common carotid artery by an electromagnetic
      blood flow probe under anesthesia before and during EECP. Blood pulse pressure,
      pulsatility index (ratio of peak pressure to end diastolic pressure) and standard
      deviation of blood pressure were calculated to evaluate the pulsatility of
      arterial blood pressure. Blood pulse flow, pulsatility index (ratio of peak flow
      to trough flow) and standard deviation of blood flow were calculated to evaluate
      the pulsatility of blood flow. Mean vascular resistance (MVR) was calculated as
      MVR = mean blood pressure/mean blood flow. Blood pulse pressure, pulsatility
      index and standard deviation of blood pressure were elevated from 30 +/- 9 mmHg,
      1.26 +/- 0.05 and 8.7 +/- 2.5 mmHg to 43 +/- 8 mmHg (P < 0.05), 1.54 +/- 0.13 and
      12.4 +/- 2.0 mmHg (P < 0.05) before and during EECP, respectively. Blood pulse
      flow, pulsatility index and standard deviation of blood flow were elevated from
      317 +/- 48 ml/min, 2.85 +/- 0.21 and 96 +/- 21 ml/min to 447 +/- 88 ml/min, 4.56
      +/- 0.90 and 131 +/- 39 ml/min before and during EECP (P < 0.05). MVR was
      decreased from 578 +/- 72 before EECP to 476 +/- 85 Wood units during EECP(P <
      0.05). These data demonstrate that EECP gives an elevation of pulsatility to
      blood pressure and blood flow, thus it may lead to the decrease of vascular
      resistance.

PMID- 12224280
TI  - [Finite element analysis of DAI animal model caused by nonimpact with half bound
      head in cats].
AB  - This study sought to make a biomechanical analysis of the diffuse axonal
      injury(DAI) animal model caused by nonimpact with half bound head in cats. A
      three-dimensional finite element model of cat's head was established. The head of
      an anesthetized cat was scanned in 2 mm section. The nods and element meshes were
      signed out according to the geometry of every section. The geometric data were
      put into the computer and the element mesh body of cat's head was established in
      vizi CAD system. The maximum stress, minimum stress and von Mises stress were
      calculated by Super SAP (93ed) finite elemental software when the force was
      loaded on the right or left side of model in zero section. The analysis showed
      that the maximum stress appeared in the anterior and posterior loaded point and
      extended to cranial base in the cranial shell. There was high stress in the brain
      surface also. Because of cerebellar tentorium, cerebral falx, petrosal bone and
      sellar process, the stress did not decrease equivalently while approaching the
      deep brain, but it was distributed in cerebral-cerebellar peduncles, brain stem,
      corpus callosum and basal ganglia area at high values. The results suggest that
      the stress caused by rotational force is widespreadly and unequivalently
      distributed in brain tissue, which is mainly effected by the cerebellar
      tentorium, cerebral falx and the irregular geometric forms of cranial bone.

PMID- 12224281
TI  - [Two mathematical models of estimating RBC membrane elastic modulus and a
      comparison of them by use of bottom attached method].
AB  - In this study on red blood cell(RBC) deformability by use of bottom attached
      method, RBC membrane elastic modulus is estimated introducing elliptical model
      and is compared with that of traditional rectangular model. As a result, RBC
      membrane elastic modulus using elliptical model is 20.9% greater than that of
      rectangular model.

PMID- 12224282
TI  - [Compliance variation following the change of longitudinal stretch ratio. A study
      on femoral artery and vein in a rabbit model].
AB  - This study was aimed to establish a rabbit model of bridging artery defect with
      autogenous vein under equal arterial and venous compliances by selecting an
      appropriate anastomosing tension based on assessing the influence of vessel's
      longitudinal strain on compliance. The exponential form P = M1 x [eM2(v-v0)-1]
      was employed to fit the blood pressure-unit volume curves under different stretch
      ratios(lambda) obtained from real curves on 13 femoral arteries and 12 veins
      whose uniaxial loading tests at longitudinal directions had been performed, then
      the quantic M = a1 lambda 5 + a2 lambda 4 + a3 lambda 3 + a lambda 2 + a5 lambda
      + a6 was done to fit M-lambda data. Results showed the differential form dv/dp =
      1/(M1 x M2 + 11.78 M2) derived from P = M1 x [eM2(v-v0)-1], and lambda reflected
      the relationship between compliance and stretch ratio (or longitudinal tension)
      under average artery pressure 11.78 KPa well. It was found that under
      longitudinal tension 1.19 g, the arterial and venous compliances were equal(0.031
      microliter/KPa) while the respective stretch ratios were 1.32 and 1.67.

PMID- 12224284
TI  - [Research on continuous measurement of blood pressure via characteristic
      parameters of pulse wave].
AB  - A new method for continuous measurement of blood pressure (BP) via selecting
      characteristic parameters of pulse wave pertinent to BP is presented in this
      paper. In order to validate the precision of the measurement, we have developed a
      Tonometer. The results of the instrument based on this method are precise if the
      subjects are at rest. This instrument could be used for BP monitoring of
      critically ill patients and in common medical researches; it might be applied to
      BP monitoring during spaceflight and in daily life after movement artifact being
      restrained.

PMID- 12224283
TI  - [Experimental study on viscoelasticity of spinal lumbar vertebrae (T12-S1) by
      simulating the operation of excising intervertebral disc and planting bone on
      back route and the operation of excising intervertebral disc and inserting fusion
      cage].
AB  - According to the physiological characteristics of lumbar vertebrae in Chinese, we
      designed and made a lumbar vertebral fusion cage of titanium and then engaged in
      its biomechanical test. T12-S1 of lumbar vertebrae from 18 fresh dead bodies were
      used. We measured the stress relaxation and the creep effects of the normal group
      (T12-S1 of intact lumbar vertebrae), the control group 1(simulating operation of
      excising intervertebral disc and planting bone on the back route) and the control
      group 2(simulating operation of excising intervertebral disc and inserting fusion
      cage). The data and stress, strain-time curves under the condition of constant
      stress and strain were obtained. Regression analysis yielded the reduced stress
      relaxation and creep functions. Finally, we analyzed and discussed the effects of
      the operation of excising intervertebral disc and planting bone on the back route
      and the operation of excising intervertebral disc and inserting fusion cage on
      the stability of spine.

PMID- 12224285
TI  - [Study on the application of number fluorescence density in detecting
      autoantibodies titer].
AB  - This study was firstly conducted to detect antinuclear antibody(ANA) titer by
      using number influorescence density analysis assay instead of serum diluted
      assay. The best camera explore time was selected. Then 4,140 ANA positive sera
      were detected to determine the relationship between number influorescence density
      (detected by number camera system Spot 32 and computer analysis software ipwin32)
      and serum diluted titer. The consistent rates in different ANA patterns used by
      the two methods were compared. 4 seconds was found to be the best explore time
      and the relationship between number influorescence density and serum diluted
      titer was 29-50 vs 1:100, 51-85 vs 1:320, 86-175 vs 1:1000, 176-215 vs 1:3200,
      216-237 vs 1:10,000. According to this standard we detected 3140 ANA positive
      sera by use of the two methods and observed a total consistency rate of 89.4%.
      The consistency rates of three ANA patterns including speckled, homogenous,
      mixture of speckled and homogenous were as high as 98.9%, 99.5%, 99.8%
      respectively. The lower consistency rate patterns included nucleolar (5.3%),
      centromere (1.8%), ribosome(12.6%) and other special patterns(0%). For practical
      purpose, number influorescence density analysis assay can be used in detecting
      the three main ANA patterns (speckled, homogeneous, mixture of speckled and
      homogenous) titer instead of serum diluted assay. The number influorescence
      density analysis assay is more objective, economical and simple than the serum
      diluted assay.

PMID- 12224286
TI  - [Number of classes from ECG and its application to ECG analysis].
AB  - The aim of this study was to detect QRS complex powers accurately. ECG was
      approximated by lines. It produced number of classes with main features of the
      whole ECG. Then these number of classes were analyzed in detail. The QRS
      detection rate reached 99.9% as validated by using single lead signals from
      MIT/BIH database. Complex powers can be recognized accurately with this method.

PMID- 12224287
TI  - [Analysis of EEG based on the complexity measure].
AB  - EEG represents the electric activity of neurons in human brain; it is of course
      repeatedly used for studying and analyzing the brain activity and the status of
      brain function. In this paper, we analyzed the patients' and normal persons' EEG
      in different physiological state, with the aid of two algorithms as a complexity
      measure. One is Kc complexity defined by Kaspar and Schuster, the other is a new
      statistical method to measure complexity sequences-Approximate entropy (ApEn). In
      our work, we analyzed two groups of persons' EEG. Six subjects in 4 different
      experimental condition are reported. From the results we can discriminate the
      different state of brain effectively: normal, being injured, and various thinking
      state. The result suggests that the two algorithms as a complexity measure could
      be regarded as valued methods in the study of EEG time series and clinical
      diagnosis.

PMID- 12224288
TI  - [Vector propagation algorithm based ECG simulation of bundle branch block].
AB  - The simulation of excitation propagation's process in human heart is one of the
      main aspects of ECG forward problem. The simulation results not only are the
      criterion of the simulation model's precision and reliability, but also have
      great value in researches and diagnoses. We performed the simulation of QRST
      waves of complete left bundle branch block (LBBB) and right bundle branch block
      (RBBB) in virtue of a vector propagation algorithm (VPA), which is accurate,
      efficient and applicable to anisotropic computer heart models. The simulation
      results accord with the actual QRST wave in clinical practice.

PMID- 12224289
TI  - [Simulation study of the reconstruction algorithm for electrical impedance
      tomography based on the sensitivity theorem].
AB  - It is the intent of this paper to develop better reconstruction algorithm for
      electrical impedance tomography (EIT). Simulation study of the reconstruction
      algorithm based on the sensitivity theorem is made and the reconstruction
      algorithm is compared with other normal algorithms. The results indicate that
      sensitivity method as a kind of static reconstruction algorithm has higher
      accuracy and speed of iteration, so it is worth researching for laboratory
      modality work.

PMID- 12224290
TI  - [Data structure representation of 3D reconstruction system of medical images and
      surface model construction].
AB  - 3D reconstruction from medical images is widely used in diagnose, radiotherapy
      surgery programming and medical research. This paper deals with the framework and
      key techniques of 3D reconstruction system of medical images. Methods of
      automatic and manual segmentation of medical images are designed. Data structure
      of the system is proposed. The system data are encapsulated in object-oriented
      paradigm and the hierarchical structure of classes is presented for
      reconstructing 3D geometry models. The 3D surface geometry model is constructed
      by using MT algorithm from the tissues extracted by automatic or manual
      segmentation. An edge collapse algorithm of mesh simplification is proposed and
      implemented, and the surface model constructed by MT algorithm is simplified by
      using this algorithm, After reduction of 90 percent triangles, the simplified
      model still maintains the original feature. It can speed up surface rendering of
      the models.

PMID- 12224291
TI  - [Wavelet feature extraction and classification of Doppler ultrasound blood flow
      signals].
AB  - The maximum frequency waveforms of Doppler ultrasound blood flow signals were
      analyzed using a multi-scale wavelet transform. The variation of maxima of
      wavelet transform modulus under various scales was extracted from the time-scale
      representation. This novel approach was applied to the analysis of Doppler
      signals from carotid blood flow. It was found that the shape of this variation
      from cases with normal cerebral vessels differed from those associated with
      abnormal cases. The curve was fitted by a polynomial, and its coefficients were
      put into a back-propagation (BP) neural network to make a classification. The
      clinical experiments showed that this approach got good performance and could be
      a new means in the clinical diagnosis of cerebral vascular disease.

PMID- 12224292
TI  - [Reconstruct three-dimensional medical images based on Internet].
AB  - This study was conducted to reconstruct three-dimensional medical images based on
      web and to achieve highly realistic display. Using the volume rendering
      techniques to reconstruct and display three-dimensional images in Java Applet
      program and utilizing signed Applets for solving security problem, We got two
      dimensional images of human organs from ultrafast CT as sources and reconstructed
      the organs configuration of heart, coronary artery, head, cervical vertebrae, and
      pelvis. This reconstruction can be run in Web browser on different kinds of
      computers and for virtual surgical planning. CONCLUSIONS: 1. Three-dimensional
      medical image reconstruction in Web browser implemented by Java Applet is
      feasible, which will prompt clinical use of three-dimensional images. 2. The
      solid conformation of human organs, especially the anatomic structure of the
      coronary artery, can be displayed by using three-dimensional reconstruction
      techniques, which may offer more information to clinics.

PMID- 12224293
TI  - [Study on automatic segmentation of color images applied to blood cells].
AB  - A hybrid segmentation algorithm is proposed for automatic segmentation of blood
      cell images based on adaptive multi-scale thresholding and seeded region growing
      techniques. Firstly, an adaptive and scale space filter (ASSF) is applied to
      image histogram and a scale space image is built. According to the properties of
      the scale space image, proper thresholds can be obtained to separate the nucleus
      from the original image and the white blood cells are located. Secondly, the
      local color similarity and global morphological criteria constrain seeded region
      growing in order to finish the segmentation of the cytoplasm. The detection
      accuracy of white blood cell is 98% and the segmentation accuracy based on the
      subjective evaluation is 93%. Test shows that this algorithm is effective for
      automatic segmentation of white blood cells.

PMID- 12224294
TI  - [ECG signal compression based on best basis of wavelet packets].
AB  - The paper reports a kind of new compression method of ECG signal. The method is
      realized by means of wavelet packets transform based on best basis performed by
      Shanon-Weaker entropy criterion. The result of simulation shows that this is an
      efficient compression method characterized by larger compression ratio and less
      loss, and the original signal can be recovered well.

PMID- 12224295
TI  - [Detection of epileptic waves in EEG based on wavelet transform].
AB  - Detection of epileptic waves in EEG is particularly helpful in the interpretation
      of the underlying process in seizures. This study is aimed at providing a new
      method for automatic detection of epileptic waves through the wavelet analysis of
      EEGs. It mainly deals with the detection of spikes or spike-waves based on
      wavelet transform. Since spikes and spike-waves contain high frequency energy,
      they will be represented in a particular scale localized in a small time window.
      According to these feature waveforms of epileptic waves, a continuous processing
      system for epileptic waveforms detection is constructed. We apply discrete
      wavelet transform on EEGs. Because of the time-frequency domain localization of
      wavelet transforms, we can get the local maximal positions across several
      successive dyadic scales of wavelet transform. And these positions indicate the
      points of sharp transitions in EEGs. Then we calculate the distance between every
      two successive maximal positions in each scale. This distance stands for the
      period of subwave. Furthermore, the distribution of subwave periods of each scale
      can be worked out. Then, comparing the distribution of normal EEG's and epileptic
      EEG's. The difference between these two waveforms provides us the criteria for
      automatic detection and classification. In order to reduce the detection
      workload, we also compare the detection efficiency of each scale. The scale that
      provides highest accuracy is selected for our automatic detection system. The
      results presented in this study show that scale 3 provides the best detection
      accuracy. So, scale 3 is deemed to be the proper scale for automatic detection.
      This system has the following advantages: (1) Reduced the workload significantly
      by selecting proper scale(s) for automatic selection; (2) Enhanced the detection
      accuracy by selecting proper criteria and threshold; (3) Capable of continuous
      detection; (4) It is also fit for the detection of other biomedical signals. This
      system showed good performance, and the initial clinical results obtained are
      also encouraging.

PMID- 12224296
TI  - [Isolation, cultivation and identification of neural stem cell from human
      embryonic CNS].
AB  - This is a study on the cultivation condition in vitro and differentiation of
      neural stem cells from human embryonic brain in order to find a way to get
      purified multipotential neural stem cells. The single cells was derived from the
      three-month embryonic brain digested with trypsin, some cells was frozen, the
      other cells were expanded with EGF and bFGF, the single-cell-clone was obtained
      by the way of limited dilution, and the serum was used to induce the cells
      differentiation. The cells were detected with the method of immunohistochemistry.
      The results showed that a lot of neurospheres could be seen in the presence of
      mitogens (both EGF and bFGF) and serum could induce neural stem cells to
      differentiate into neurons, astrocytes, and oligodendrocytes. These indicate that
      the survival and proliferation of neural stem cells rely on the cooperation of
      EGF and bFGF. The neural stem cells can also be harvested from the frozen cells.

PMID- 12224298
TI  - [Development of conductance measurement technique for permeability of monolayer
      endothelial cells].
AB  - The conductance measurement method of endothelial permeability has been
      established by the principle that there is direct ratio between conductance and
      filter area, and has been compared with the albumin filter method. The results
      show that there is close correlation between conductance and filter area, the
      conductance measurement can be used for the detection of the monolayer
      endothelial cells permeability. The combination of the conductance measurement
      and the albumin filter measurement method can accurately reflect the permeability
      change in severity and scope.

PMID- 12224297
TI  - [Human peripheral blood monocyte derived dendritic cell culture and mature
      regulation].
AB  - Mature dendritic cells are potent antigen-presenting cells that initiate primary
      immune responses, while immature dendritic cells have quite different properties
      from mature dendritic cells and are tolerance inducer actually. Here we describe
      the method of using monocyte condition medium to generate dendritic cells of
      different maturation phases from nonproliferating progenitors in human peripheral
      blood. The procedure involves two steps. The first step(or priming phase) is to
      work on a 6-7-day culture of plastic-adherent blood monocyte in medium supplement
      with GM-CSF and IL-4. The second step (or differentiation phase) requires the
      exposure to monocyte conditioned medium. Only the dendritic cells generated by
      the first step are actually immature, with strong immature dendritic cell
      features such as active endocytosis, the same expression of monocyte marker CD14,
      and much of the MHC class II still lies within intracellular compartments (MIIC).
      The second stage dendritic cells have all the features of mature dendritic cell,
      including a stellate shape, nonadherence to plastic, the expression of dendritic
      cells restricted marker CD83, and very strong T cell stimulatory function. All of
      these dendritic cell properties are retained for at least 3 days when the
      cytokines are removed, suggesting that these populations are stable and
      terminally differentiated. Since progression from immature to mature dendritic
      cell is entirely dependent on exogenously added growth factor such as monocyte
      condition medium, the peripheral blood monocyte may help to harness synchronized
      population of mature and immature dendritic cells for studies or therapies.

PMID- 12224299
TI  - [Generation of CD14+ dendritic cells in vitro with GM-CSF and IL-4].
AB  - This study was conducted to get high quality and sufficient numbers of mature
      dendritic cells from healthy donor peripheral blood. The experiment began on
      culturing of plastic-adherent monocytes isolated from healthy donor peripheral
      blood with granulocyte-monocyte clony-stimulating factor (GM-CSF 150 ng/ml) and
      interleukin 4 (IL-4 800 U/ml) without fresh medium feeding and cytokines for 7
      days. After 7 days, CD14+ monocytes not only differentiated into high purity DC
      but also expressed HLA-I and HLA-II molecules, costimulating molecules, adherent
      molecules and its progenitor marker CD14 molecule highly. These cells displayed
      all phenotypic and morphologic characteristics of mature dendritic cells and were
      most potent stimulatory cells in allogeneic mixed leukocyte reactions. The
      endocytosis ability of these DCs peaked at the third day in culture and decreased
      remarkably afterwards. These results provide evidence for the first time that
      CD14+ monocytes differentiated in vitro from peripheral blood monocytes exhibit
      dendritic cells characteristics and still express its progenitor marker CD14
      molecules highly. The results of this experiments may facilitate further studies
      of CD14+ DC and its clinical applications.

PMID- 12224300
TI  - [Expression and purification of human papillomavirus type16 L1 protein in a
      prokaryotic expression system].
AB  - This study was intended to establish a method of purification of HPV16 L1 protein
      expressed in a prokaryotic system and to obtain the purified protein. The
      prokaryotic expression vector pGEX-4T-1-HPV16 L1 was constructed and transformed
      into E. coli BL21 cell, and induced by 1 mM IPTG to express HPV16L1 protein. The
      inclusion bodies were isolated and solubilized with 8 M urea. After the urea was
      removed by gradual dialysis, the denatured L1 protein were renatured and then
      were purified by affinity chromatography. The results showed that HPV16L1 protein
      formed inclusion bodies in bacterial expression system, suggesting that this
      assay can be used to purify HPV16L1 protein and hence provide a basis for
      studying the applications of HPV16 L1 protein.

PMID- 12224301
TI  - [Cloning of AE1-c-end cDNA and construction of its expression plasmid for yeast
      two-hybrid system].
AB  - In this study, about 350 bp cDNA fragment was amplified by PCR. After being
      sequenced, the AE1-c-end gene fragment was cloned into EcoR I-Pst I site of
      pGADT7 to form AD ends in the yeast two-hybrid system. The recombinant plasmid
      was transformed into yeast AH109, and the expression in the yeast was observed.
      The results demonstrate that AE1-c-end was obtained. pGADT7-AE1-c-end has no
      toxic effect on the yeast. It can serve as a target gene of yeast two-hybrid
      system.

PMID- 12224302
TI  - [A study on central zone contour of tooth-crown vesticular surface among young
      people with normal occlusion].
AB  - To evaluate the effects of preadjusted bracket base shape, the morphology of
      tooth surface where bracket locates, and the suitability relevant to location of
      bracket on the preadjusted edgewise appliance technique. 1 vertical curve and 3
      horizontal curves of the clinical crown surface of anterior teeth and bicuspid
      teeth were measured with the precise contour instrument on the 60 plaster models
      of the subjects who have normal occlusion in Sichuan province. It was found that
      variation of identical curve exists at the different heights between the teeth
      and between the individuals; the surface of the central zone of tooth-crown
      gradually protrudes from incisors to bicuspid teeth in the vertical direction,
      and the mesial contour of cuspid is more prominent than the distal in the
      horizontal direction. CONCLUSION: The 4 mm X 3 mm contour of the vestibular
      central zone of identical tooth-crown in different individuals is fairly stable;
      it is suitable for the location of preadjusted brackets. The vertical shifts of
      brackets could change the preadjusted torque value and the design of cuspid
      bracket should have the distinction between mesial and distal shape.

PMID- 12224303
TI  - [Effect of different types of counterion on the electronic structure of an
      antitumor polyoxomolybdate [Mo7O24]6-].
AB  - The electronic structure of a Lindqvist type [Mo7O24]6- anion with 5 different
      types of counterion (K+, Na+, NH4+, [NH3Pr]+ and [NH3Pri]+) was calculated by
      using the Discrete Variational Method coupled with Density Functional Theory (DFT
      DVM). It could be concluded through variance analysis to the calculated results
      that the type of counterion does not influence remarkably the electronic
      structure of [Mo7O24]6- anions. Perhaps it can be used to explain the experiment
      fact that the polyoxomolybdate structure of the Mo7O24 framework is apparently of
      critical significance to antitumor action. On these grounds we forecast that two
      other lindqvist type heptamolybadates(their counterions are Na+ and [NH3Pr]+
      respectively) may also exhibit antitumor activities.

PMID- 12224304
TI  - [Assessing the significance of platelet count to in-vitro hemolytic test by
      roller pump].
AB  - This study was directed at estimating the value of platelet count in the course
      of in-vitro hemolytic tests by roller pump. Five paired in-vitro tests were
      conducted using the POLYSTAN pump(group A) and COBE pump(group B). The pumps ran
      16 hours. The samples for platelet count and plasma-free hemoglobin were taken
      before pumping, and every 2 hours after 4 hours of pumping. The 2 groups'
      platelet count and plasma-free hemoglobin levels were found to be linearly
      increasing with the hours of pumping and linear regression analysis showed the
      platelet count and plasma-free hemoglobin were positively correlated. These data
      suggested that platelet count could be used as an index in evaluating the in
      vitro hemolytic properties of blood pumps.

PMID- 12224305
TI  - [Treatment of patients with Graves' ophthalmopathy by immunosuppressive agent and
      99Tc-MDP].
AB  - The purpose of this study was to evaluate the efficacy of immunosuppressive
      agents, 99Tc-MDP and both of them in treating patients with Graves'
      ophthalmopathy(GO). The efficacy was evaluated by randomized controlled trial
      involving a total of 66 patients. In 22 patients treated with immunosuppressive
      agents, the general efficacy rate was 19/22, the incidence rate of serious side
      effect was 8/22. In 20 patients treated with 99Tc-MDP, the general efficacy rate
      was 17/20, the incidence rate of serious side-effect was 2/20. In 24 patients
      treated with immunosuppressive agents and 99Tc-MDP, the general efficacy rate was
      22/24, the incidence rate of serious side-effect was 2/24. The results suggested
      that in the treatment of Graves' ophthalmopathy, when satisfactory efficacy was
      obtained, the serious side-effect and 'rebound' of symptom could be avoided by
      using immunosuppressive agents in combination with 99Tc-MDP.

PMID- 12224306
TI  - [Synthesis and characteristics of porous hydroxyapatite bioceramics].
AB  - The macroporous structure of human bone allows the ingrowth of the soft tissues
      and organic cells into the bone matrix, profits the development and metabolism of
      bone tissue, and adapts the bone to the change of load. There is great
      requirement for artificial biomimic porous bioactive ceramics with the similar
      structure of bone tissue that can be used clinically for repairing lost bone.
      Fine hydroxyapatite (HAp) powder produced by wet chemical reaction was mixed with
      hydrogen peroxide (H2O2), polyvinyl alcohol, methyl cellulose or other pores
      making materials to form green cake. After drying at low temperature (below 100
      degrees C) and decarbonizing at about 300 degrees C-400 degrees C, the spongy
      ceramic block was sintered at high temperature, thus, macroporous HAp bioceramic
      with interconnected pores and reasonable porosity and pore-diameter was
      manufactured. This kind of porous HAp bioceramics were intrinsically
      osteoinductive to a certain degree, but its outstanding property was that they
      can absorb human bone morphogenetic proteins and other bone growth factors to
      form composites, so that the macroporous HAp bioactive ceramic has appropriate
      feasibility for clinical application. From the point of biomedical application,
      the recent developments in synthesis and characteristics investigation of
      macroporous HAp are reviewed in this paper.

PMID- 12224307
TI  - [Application of biodegradable polyhydroxybutyrate in medicine and tissue
      engineering].
AB  - The technology of synthesis, extraction and modification of biodegradable
      polyhydroxybutyrate (PHB) is introduced briefly in this article. It is also
      summarized that the research progress in application of PHB in drug delivery and
      tissue engineering.

PMID- 12224308
TI  - [5-Aminolevulinic acid esters based photodynamic therapy].
AB  - As exogenous ALA (5-aminolevulinic acid) esters can induce the production and
      accumulation of endogenous photosensitizer PpIX (protoporphyrin IX) in tumor
      tissues more effectively, they have been the most active photosensitizer prodrug
      in PDT(photodynamic therapy) field. In this article, along with the procedure of
      ALA esters based PDT, some primary mechanism and experimental results were
      considered, which include: first, cellular uptake of ALA esters and its
      conversion into ALA; second, the production and accumulation of endogenous
      photosensitizer PpIX induced by eNdogenous ALA esters; last, the
      photosensitization of PpIX.

PMID- 12224310
TI  - [Physiological and pathologic implications for zero-stress state of the
      esophagus].
AB  - The zero-stress state of the esophagus is the state in which the esophagus is
      stress-free. It is in close correlation with physiology and pathology of the
      esophagus. The purpose of the review is to describe briefly the basic theory of
      zero-stress state and its physiological and pathologic implications in the
      esophagus.

PMID- 12224309
TI  - [The advance of research for biocompatibility of medical polyurethanes].
AB  - Polyurethanes are popularly used in cardiovascular and other biomedical fields
      due to their good biocompatibility as well as mechanical properties. But they are
      subject to biodegradation in vivo for a long time, and cause inflammation, so
      improving the biocompatibility of medical polyurethanes is an important subject
      of biomaterials. Recent researches have focused on biological modelling of
      biomaterials for improving the biocompatibility of polyurethanes. This paper
      reviews two main methods for improving biocompatibility of polyurethanes
      endothelial cells seeding and mimic biomembrane (phospholipid surface), and
      summarizes the main procedures and questions of these two methods.

PMID- 12224311
TI  - [Experimental methods for mechanically stimulating the cells in vitro].
AB  - Cellular mechanics is a branch of tissue engineering and cellular engineering. As
      one of the important method, loading different mechanical stimuli to culturing
      cells in vitro so as to study the influence that the stress has on the cells is
      one of the important fields of cellular mechanics. This paper reviews the
      experimental methods for mechanically stimulating the cells in vitro, according
      to the different loading modalities, the methods can be categorized into
      micropipette aspiration, compression loading, substrate distention, fluid shear,
      etc. And it also points out their advantages and disadvantages.

PMID- 12224312
TI  - [The progress in research for human pulse system modeling and pulse condition
      information analysis].
AB  - This article introduces the significance, methods and applications in human pulse
      study, with an emphasis on the history, current situation and progress of pulse
      system modeling and pulse signal analysis. The problems in present study and the
      methods for the future investigations were analyzed.

PMID- 12224313
TI  - [Research and development on microwave sterilization].
AB  - This paper reviews recent research and development on microwave sterilization,
      including the experiments of sterilization effects, the influence of microwave
      radiating on the media parameters, the development of microwave sterilizers and
      the study of sterilization mechanism. Many results show that the method of
      microwave sterilization is more easy-to-perform, economical and reproducible than
      the conventional autoclaving method. It is necessary to study the sterilization
      conditions through the experiments for different media and bacteria. The research
      on sterilization mechanism, especially non-thermal sterilization mechanism is
      still a hotpoint.

PMID- 12224315
TI  - [Research on embryonic stem cells].
AB  - Embryonic stem cells are derived from inner cell mass of the preimplanted
      blastocyst or from primordial germ cells of the early embryos, with the capacity
      of unlimited growth and differentiation potential. Embryonic stem cells(ES cells)
      can differentiate into all kinds of cells and organs under proper condition. Due
      to this characteristics ES cells have the attractive prospect in basic research,
      transplantation and gene therapy.

PMID- 12224314
TI  - [The research progress of using electroporation therapy in treatment of tumor].
AB  - In these years, the electrical technology is widely applied in the study of
      biomedical engineering. Using electroporation therapy (EPT) to treat tumor is
      associated with biomedical engineering, electrical new technology, computer
      technology and microelectronic technology, which is a new marginal subject. Many
      experts have studied the mechanism and clinical treatment of the cell membrane
      electroporation phenomenon under electrical fields. These researches have shown
      that the membrane electroporation can stimulate the transport and intake of
      various drugs, which improves the tumoricidal effect of these drugs. The
      researchers have also been exploring the phenomenon that irreversible electrical
      breakdown (IREB) of cell membrane under high electrical fields and steep pulses
      leads to the death of tumor.

PMID- 12224316
TI  - [Advances in research on ion-channel gating mechanism].
AB  - The history and current situation of cell membrane ion-channel gating mechanism
      study were reviewed, with an emphasis on the application and the latest
      developments of kinetic model in gating mechanism study; the problems in present
      study and ion-channel gating mechanism kinetics model for future investigations
      were finally discussed.

PMID- 12224318
TI  - [Multiagent system for individual artificial hip joint].
AB  - Based on the introduction of multi-agent and individual artificial hip joints,
      this paper reports a multi-agent design system for individual artificial hip
      joints. Three agents are defined, the first is to optimize the diameter of hip
      joint, the second for FEM, the third for simulation between the prosthesis and
      acetabulum cup. The paper lays emphasis on the second agent.

PMID- 12224317
TI  - [Rapid manufacturing of degradable porous polymer bone scaffold].
AB  - Making bone scaffold through tissue engineering method presents a new choice for
      both the patients and the doctors of orthopaedics. The biodegradable polymer PLA
      is chosen to make porous fundus scaffold jetting through special designed nozzle
      on multi-functional rapid prototyping machine controlled by computer according to
      the CT data CAD model. The scaffold is then chemically aggregated to compound
      with collagen-hydroxyapatite, and the ideal bone repair material is obtained.
      Animal experiment has indicated the correctness of this conclusion.

PMID- 12224319
TI  - [Extension of cardiac monitoring function by used of ordinary ECG machine].
AB  - This paper deals with a portable monitor system on liquid crystal display (LCD)
      based on this available ordinary ECG machine, which is low power and suitable for
      China's specific condition. Apart from developing the overall scheme of the
      system, this paper also has completed the design of the hardware and the
      software. The 80c196 single chip microcomputer is taken as the central
      microprocessor and real time electrocardiac single is data treated and analyzed
      in the system. With the performance of ordinary monitor, this machine also
      possesses the following functions: five types of arrhythmia analysis, alarm,
      freeze, and record of automatic pappering, convenient in carrying, with alternate
      current (AC) or direct-current (DC) powered. The hardware circuit is simplified
      and the software structure is optimized in this paper. Multiple low power designs
      and LCD unit design are adopted and completed in it. Popular in usage, low in
      cost price, the portable monitor system will have a valuable influence on China's
      monitor system field.

PMID- 12224320
TI  - [Analysis of antibacterial activity of a new antiseptic for therapy of
      maxillofacial inflammations].
AB  - Clinical and experimental studies of polydimethyldiallylammonium chloride
      (PDMDAAC) experimentally validated the choice of optimal concentration and
      composition of this agent. The results indicate a high antiseptic activity of 1%
      PDMDAAC and the possibility of using it in local therapy of periodontitis and
      posttraumatic infection.

PMID- 12224321
TI  - [Sialodiagnostika-2000, an automated system for differential diagnosis of the
      salivary glands chronic diseases].
AB  - Automated system for differential diagnosis of chronic diseases of the salivary
      glands Sialodiagnostika-2000 is based on an original differential diagnostic
      algorithm. Complex differential diagnosis of chronic diseases of the salivary
      glands can be carried out using this software. Tentative and final clinical
      diagnosis can be made on the basis of the results of examinations using the
      optimal complex of accessory methods. The authors claim that Sialodiagnostika
      2000 makes the experience gained by the leading specialists available for
      practicing dentists and thus improves the diagnosis of diseases of the salivary
      glands.

PMID- 12224322
TI  - [Lymphotropic antibacterial therapy for preventing inflammatory complications of
      mandibular fractures].
AB  - We propose a new method of preventing infectious and inflammatory complications
      of mandibular fractures crossing the dental arch. The method was based on
      regional lymphotropic administration of antibacterial drugs to the mastoid region
      of the temporal bone. This technique was applied in combined therapy of 51
      patients. Comparative analysis with the control group revealed high efficacy of
      the given method. Basing upon clinical experience we worked out indications to
      the regional lymphotropic antibacterial therapy as a part of complex prophylaxis
      of posttraumatic mandible osteomyelitis.

PMID- 12224323
TI  - [Early dental implantation using brephobone allotransplants].
AB  - The installation of titanic screw two-stage dental implants and simultaneous
      alveolar ridge plasty with demineralizated lyophilizated bone allografts was
      performed in early terms--3-17 weeks after the tooth extraction. The tissue
      shaving picked under the implant bed preparation was exposed to histology
      analysis to determine the initial conditions for early implantation. 23 patients
      were operated on and 41 implants were installed. The successful osteointegration
      was reached in 95.1% cases. The full restoration of bone density and thickness
      after complete treatment was confirmed by computer tomography.

PMID- 12224324
TI  - [Results of the facial skull bone defects and deformations repair by modern
      methods for plasty and fixation of bone fragments].
AB  - Methods of reconstructive maxillofacial operations bringing about the best
      functional and esthetic results are analyzed. Surgical methods for repair of
      maxillofacial bone defects and deformations with the use of transplants and
      different methods of their fixation depending on the tissues at the site of
      defect (deformation) in patients with acquired and congenital abnormalities of
      the facial skull have been developed and are used at Central Institute of
      Dentistry. Osteosynthesis using titanium constructions and compression
      distraction devices is acknowledged as an effective method of bone repair
      operations on the face. It notably reduces the duration of operation and prevents
      the relapse of the deformation. Analysis was carried out on extensive clinical
      data (more than 1000 patients), which allowed an objective evaluation of remote
      results of plastic repair of bones and helped define the indications and
      contraindications for such operations.

PMID- 12224325
TI  - [Hormonal correction in combined therapy of temporomandibular joint dysfunction
      in women].
AB  - Pain dysfunction syndrome of the temporomandibular joint (TMJ) in women is often
      accompanied by mammary and reproductive disorders associated with endocrine
      disturbances. 30 female patients aged 19-35 years suffering from of the pain
      dysfunction syndrome TMJ combined with intact dentition and orthognathic
      occlusion were studied. Dental examination was followed by gynecologic
      examination. According to the treatment the patients were divided into 2 groups.
      Group I included women who were administered conventional treatment (orthopedic
      treatment, drug and physiotherapy). In group II patients conventional therapy was
      also combined with monophase oral contraceptive "Femoden". Efficacy of treatment
      in group I was 46.67%; while group II patients showed a 100% favourable effect.
      Besides, combination of dental and gynecologic therapy was found to exert a 2.1
      times more stable clinical effect us compared to conventional treatment. Hormone
      correction in women with reproductive pathology results in prolonged control of
      the pain dysfunction syndrome TMJ due to steroid normalization (hypothalamic,
      hypophysial, ovary steroid normalization) and has no side effects.

PMID- 12224326
TI  - [Cicatricial deformation of the face after herpes simplex infection].
AB  - One of the most wide-spread virus infections causing various diseases of dermal
      integuments, central and peripheric nervous system, viscera, eye, oral cavity and
      genitalia is Herpes simplex (HS). The clinical case of a 10-year child who had at
      early age HS infection complicated by extensive cicatrical deformation of frontal
      temporoparietal skin is reported. The cicatrical deformation has caused
      disfunction of periorbital tissues. Principles of treatment are considered and
      practical references are given.

PMID- 12224327
TI  - [Microbiological validation of the choice of basic plastic for removable
      dentures].
AB  - Adhesion of obligate and facultative anaerobic bacteria, favoring the development
      of oral inflammatory diseases, including the cariesogenic and periodontogenic
      bacteria and Candida albicans fungi, isolated from patients with periodontitis,
      to 13 basic materials used in removable denture making, was studied. The adhesion
      of all bacteria (Streptococcus sanguis, Prevotella melangogenica, Fusobacterium
      nucleatum, Corynebacterium xerosis) and fungi to hot polymerization basic
      materials was the maximum. The most perspective basic plastic for clinical use
      (preserving intact oral microbiocenosis and preventing stomatitis induced by
      denture wearing) are cold polymerization materials, such as Redont-03, Dentoplast
      Breden, Leocryl, and UHF polymerization materials Acron GC, AKR-MV, and Etakril
      02.

PMID- 12224328
TI  - [Displacement of the titanium endoprosthesis of the mandibular condyle process
      towards the middle cranial fossa and method for its repair].
AB  - A clinical case is presented: endoprosthesis of the articular depression of the
      temporomandibular joint (TMJ) was used in the treatment of a patient with a
      complication which developed several years after insertion of an isolated
      endoprosthesis of the mandibular condylar process. This case is presented as a
      proof of the efficiency of a complete TMJ endoprosthesis.

PMID- 12224329
TI  - [Dynamic method for measuring the periodontal area].
AB  - The study was carried out on 21 teeth before and after their removal in 9
      patients. Mechanical parameters of the dental supporting-retaining system were
      studied with a two-parametrical periodontometer, which evaluates the tooth
      mobility and angle of losses, characterizing the internal friction in the tooth
      periodontium-bone system. The in vitro area of the periodontium was evaluated
      using millimeter paper. A direct relationship between the angle of losses and
      periodontal area was revealed. The authors suggest using a coefficient of
      propotionateness between the periodontal area and angle of losses; this
      coefficient does not depend on the tooth mobility and periodontal area.

PMID- 12224330
TI  - [Functional state of maxillofacial muscles in patients with dentition defects
      depending on the number of missing antagonist pairs].
AB  - Changes in the functions of maxillofacial muscles were studied in patients with
      first-class defects of dentition. The mean biopotential of masticatory muscles in
      patients lacking 1 antagonist pair is 30.4% and in those lacking 4 pairs 59.5%
      lower vs. the norm. The bio-excess coefficient is 23.7% decreased in subjects
      lacking 1 antagonist pair and 52% decreased in those lacking 4 antagonist pairs.
      Hence, the function of maxillofacial muscles depends on the extent of dentition
      defect.

PMID- 12224331
TI  - [Biomechanical fundamentals of the dentofacial anomalies treatment].
AB  - The results of biomechanical investigations of the central incisor having the
      formed root by mathematical modeling methods are presented. The centre of
      resistance of a tooth, the optimal horizontal forces of action and reaction were
      determined. The advantage of discontinuous forces due to amortization influence
      of periodontal ligament fluid was biomechanically proven. The recommendations
      which were given after experiments and mathematical modelling were used during
      orthodontic treatment of 30 patients (12-18 years) with anomalies of dental
      arches and occlusions by mechanically acting appliances and combined ones. At the
      end of the treatment 90.0% of the patients had physiological teeth angulation,
      93.3% had the physiological torque. However using the removable single-jaw
      mechanically acted appliances had not lead to improvement of the first Angle
      Endruce's key in 50.0% of the patients and to elimination of gaps between teeth
      in 23.4% of the patients.

PMID- 12224332
TI  - [Screening diagnosis of membrane-destructive process in children with
      maxillodental abnormalities and gastrointestinal diseases].
AB  - Native mixed saliva of 86 children with congenital and acquired dentognathic
      system deformations and gastrointestinal tract diseases was investigated by
      specially devised method using optical reflecting microscope Neophot-2. In
      cytological preparations of mixed saliva all the cell elements were with signs of
      significant edema and cytolysis. In detritus different structures of lipid
      aggregations prevailed. The block of cellular immunity defense factors was
      detected. 3 grades of membrane destructive process caused by structure functional
      peculiarities of cytoplasmatic membranes organization were identified.

PMID- 12224333
TI  - [Self-evaluation of dental health by elderly people. Functional and psychosocial
      problems].
AB  - The purpose of the study was to establish personal estimation of population over
      60 years of age of their dental health. The study was performed in 1999 and
      included 497 persons--206 male and 291 female. The results show that disorders in
      biting, chewing and taking solid food begin with the loss of 4-6 teeth. Disorders
      in speech start after the loss of 7 and more teeth. In case of 20 and more
      retained teeth, considerable part of persons do not feel disorders in main
      functions of chewing system. In case of acceptable shortened dental arches
      (missing some of all of the molars and retained all the rest teeth of dentition),
      together with lack of serious functional disorders, all persons with such status
      give good or satisfying self-rating of oral health.

PMID- 12224334
TI  - [Adhesive bridge dentures: from creation to the present time].

PMID- 12224335
TI  - [Moscow State Medical Stomatological University: 80 years since foundation. Pages
      from history].

PMID- 12224336
TI  - [Morphogenic processes in dosed distraction].
AB  - Dosed distraction of bone regenerate is paralleled by distraction of soft tissues
      (skin, muscles, nerves, etc.), which is particularly obvious during liquidation
      of medium-sized and extensive mandibular defects. Such distraction of soft
      tissues leads to their regeneration and growth. However regeneration of soft
      tissues is paralleled by dystrophic processes, which are never observed in bone
      regenerate. Dosed distraction can be used in repair of combined bone and soft
      tissue defects and deformations of the face of different etiology.

PMID- 12224337
TI  - Health care industry informs FDA of bar-code needs.

PMID- 12224338
TI  - Study finds intensive coaching improves antiretroviral therapy adherence.

PMID- 12224339
TI  - Two more states enact CDTM laws.

PMID- 12224340
TI  - JCAHO sets patient-safety goals for 2003.

PMID- 12224341
TI  - Federal program helps more hospitals provide drugs to needy patients.

PMID- 12224342
TI  - Update on the management of dyslipidemia.
AB  - The third edition of guidelines from the National Cholesterol Education Program
      Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in
      Adults (Adult Treatment Panel III [ATP III]) is discussed. The most recent
      classifications for low-density-lipoprotein (LDL) cholesterol, high-density
      lipoprotein (HDL), total cholesterol, and triglycerides are provided. LDL
      cholesterol goals, cardiovascular risk assessment, therapeutic goals, and
      pharmacologic treatment options are discussed for both primary and secondary
      prevention of cardiovascular disease. In addition, the management of dyslipidemia
      in patients with diabetes and metobolic syndrome is addressed, and the
      differences between the old and new guidelines are highlighted. The ATP III
      guidelines may help health care professionals to better screen and categorize
      patients on the basis of their coronary heart disease (CHD) risk. The updated
      guidelines recommend more intensive lipid-lowering treatments for primary
      prevention in patients with two or more risk factors.

PMID- 12224343
TI  - Pharmacogenomics and infectious diseases: impact on drug response and
      applications to disease management.
AB  - The impact of pharmacogenomics on the prevention, diagnosis, and treatment of
      infectious diseases is discussed. The application of pharmacogenomics to
      infectious diseases requires consideration of the genomes of both the pathogen
      and the host. The pathogen's genome may be used for antigen identification, to
      identify infecting organisms, and to determine antimicrobial resistance.
      Diagnostic tool development and vaccine design can be aided by knowing which
      portions of a pathogen are important antigenic determinants. The unique genetic
      makeup of a pathogen can facilitate its identification as an augmentation to the
      traditional culture. Important genes conferring resistance to antibiotics can be
      detected, and this information can be used to choose appropriate antibiotic
      therapy. The genome of the host may reveal susceptibility genes and new drug
      targets that may be used in the treatment of infectious diseases. Thus far,
      polymorphisms in genes of the host immune system have been associated with
      susceptibility to infections and response to treatment. Examples of these
      findings will be described. Pharmacogenomics has the potential to revolutionize
      the prevention, diagnosis, and treatment of infectious diseases.

PMID- 12224344
TI  - Evaluation of pharmacists' services for hospital inpatients.
AB  - Patient satisfaction with pharmacist-conducted weekly medication-education
      classes and the underlying factor structure of the evaluation items are
      described. The pharmacist service consisted of weekly, one-hour classes for
      headache sufferers in a tertiary headache clinic's hospital unit. One pharmacist
      taught all of the classes and conducted them in the same manner each week, using
      the Indian Health Service patient-counseling technique. The classes included both
      lecture and one-on-one interactions. Any patient admitted to the hospital's
      headache unit was eligible to participate in the study. Patients were asked to
      complete a survey at the end of the class, evaluating the service in terms of
      performance, disconfirmation of expectations, affect, equity, and self-efficacy
      by rating three statements about each of these on a 7-point scale, where 1 = very
      strongly disagree and 7 = very strongly agree. Exploratory factor analysis was
      used to investigate the degree to which these five evaluation areas were distinct
      constructs. A total of 157 patients attended a medication-education class during
      the study period. Of these, 153 (97%) provided usable data. Respondents favorably
      evaluated the pharmacist service, as the means were significantly greater than
      the scales' midpoint scores (p < 0.001). Factor analysis results suggested that
      covariation in the data was best described by four factors rather than five: (1)
      performance, (2) disconfirmation of expectations, (3) equity, and (4) self
      efficacy. Inpatients attending pharmacist-conducted weekly medication-education
      classes favorably evaluated the pharmacist service. Four different
      conceptualizations of patients' evaluations were identified.

PMID- 12224345
TI  - Reteplase for clearance of occluded venous catheters.

PMID- 12224346
TI  - Structuring an indigent care pharmacy benefit program.

PMID- 12224347
TI  - Drug selection for safety-net-provider formularies.

PMID- 12224348
TI  - Providing for the pharmaceutically indigent.

PMID- 12224349
TI  - Nursing notes are key to limitations issue.

PMID- 12224350
TI  - The risk of nurse-midwives assessing patients by phone. Case on point: Ali v.
      Community Health Care Plan, Inc., 801 A.2d. 775-CT (2002).

PMID- 12224351
TI  - CA: nurse who falls in hospital is non-suited: can RN testify her fall caused
      meniscus tear?

PMID- 12224352
TI  - WA: nurse-expert's testimony inadmissible: lack of expert testimony re cause of
      death fatal.

PMID- 12224354
TI  - Practical matters. CHA scales back zero-tolerance on uninsured. Interview by
      Vince Galloro.

PMID- 12224353
TI  - Promised a promotion?: get it in writing! Case on point: Tremlett v. Aurora
      Health Care, Inc., 2002 WL 1424224 N.W.2d-WI.

PMID- 12224355
TI  - An idea is born. GNYHA morphs defunct site into streaming tool.

PMID- 12224356
TI  - New leader, new mission. Heightened focus on bioterrorism poses unique challenges
      for CDC's new chief.

PMID- 12224357
TI  - No more risky business. Promina out of capitated contracts by year-end.

PMID- 12224358
TI  - The way to pay for rural care. Cost-based payment would stabilize finances for a
      class of troubled hospitals.

PMID- 12224359
TI  - Web survey. June results: 'prescription-drug spending'.

PMID- 12224360
TI  - In search of a breakthrough. Small medical devicemakers contend it's tough to
      crack the group purchasing domain; GPOs say they're open to true innovation.

PMID- 12224361
TI  - New product on the shelves: nurses. GPOs sign contracts with staffing firms to
      offer hospitals 'one-stop shopping'.

PMID- 12224362
TI  - Too little too late or enough? With the Nurse Reinvestment Act signed, the
      industry questions how much funding the legislation will provide to ease nursing
      shortage.
AB  - The long-awaited Nurse Reinvestment Act was signed into law last week by
      President Bush, but still the healthcare industry is in limbo about just how much
      help it will get at the federal level to help reverse the nation's nursing
      shortage. After overcoming the hurdle of creating new incentive programs,
      hospitals still have to persuade Congress to appropriate funding.

PMID- 12224363
TI  - Medicare not perfect, not a total mess either. Report by experts finds problems
      but rejects need for complete administrative overhaul.

PMID- 12224364
TI  - Providers win. HHS won't expand use of post-acute transfer policy.

PMID- 12224365
TI  - The nephrology nurse's role in improved care of patients with chronic kidney
      disease.
AB  - The care of chronic kidney disease (CKD) patients is suboptimal. This article
      discusses how nephrology nurses can contribute to multidisciplinary clinics that
      work in collaboration with primary care providers to identify and manage patients
      with early CKD. This article will describe the importance of the nephrology nurse
      as a resource for improved patient outcomes and for the implementation of
      federal, professional, and corporate CKD initiatives.

PMID- 12224366
TI  - Development of the thirst distress scale.
AB  - This article describes the development of a 6-item instrument that measures
      thirst distress. Items were developed following open-ended interviews with 10
      subjects, a literature review, and development of a conceptual definition of
      thirst. A panel of experts established content validity. A convenience sample (N
      = 247) of adults receiving outpatient hemodialysis completed the scale. A panel
      of experts was used to assess content validity. Item analysis was used to select
      unrelated or redundant items for deletion. Cronbach's alpha was .78. Construct
      validity was supported by confirmatory and exploratory factor analysis. Positive
      relationships between thirst distress and, respectively, thirst intensity and
      interdialytic weight gain provided additional evidence of construct validity.
      Overall, these preliminary data indicate that the thirst distress scale has
      sufficient reliability and validity for use in clinical studies.

PMID- 12224367
TI  - Initiation into a dialysis-dependent life: an examination of rites of passage.
AB  - The purpose of this article is to explore the conceptual and empirical
      application of the rites of passage model in contemporary health care for those
      who are dialysis dependent. This study used a collective case study design and
      narrative methodology. A purposive sample yielded 10 participants who were
      receiving dialysis. Prolonged observation and immersion in the culture of
      dialysis dependency occurred in the settings of the participants' home and renal
      units in Queensland, Australia. In-depth interviews and narrative analysis were
      used. The criteria of reflexivity, voice, and verisimilitude established the
      rigor of the study. The findings illuminated the three stages of rites of passage
      (ROP), separation, liminality, and reincorporation, with each stage evident in
      the participants' stories. Commencing dialysis is an initiation that delineates
      the transition from one social status to another. It is argued that there is a
      metaphoric usefulness of the application of the ROP model that might influence
      the quality of care to dialysis initiates.

PMID- 12224368
TI  - Lytic therapy in central venous catheters for hemodialysis.
AB  - Over the past 2 decades the use of central venous catheters (CVCs) for
      hemodialysis has become commonplace. While these devices have provided much
      needed temporary access to the bloodstream, they often become thrombosed and
      require procedures to restore patency. This article examines the lytic enzymes
      that are currently available and focuses on the assessment and treatment of
      thrombosis.

PMID- 12224369
TI  - A preference study: calcium acetate tablets versus gelcaps in hemodialysis
      patients.
AB  - End stage renal disease (ESRD) patients are frequently noncompliant with
      phosphate binder therapy. This noncompliance may lead to uncontrolled
      hyperphosphatemia, resulting in an increased risk of mortality via the
      development of serious comorbid conditions. A new gelcap form of calcium acetate
      has been introduced for control of hyperphosphatemia. This single center,
      unblinded study compared calcium acetate tablets versus calcium acetate gelcaps
      with regards to patient preference and ease of swallowing. Twenty-two patients
      were randomized to receive 1 day of treatment with calcium acetate tablets,
      followed by 1 day of treatment with calcium acetate gelcaps, or vice versa.
      Following completion of the treatment period, the patients were given a
      questionnaire to complete that asked them to compare their experience with both
      treatments. Twenty patients completed the study. Eighteen patients preferred the
      gelcap to the tablet in all preference categories. The same 18 patients responded
      that the gelcap was easier to swallow than the tablet. Because of the evidence
      documenting the noncompliant behavior of ESRD patients with respect to their
      binder therapy, efforts made to give the patients a more satisfying alternative
      can aid in improving compliance.

PMID- 12224370
TI  - Evaluating iron status in hemodialysis patients.
AB  - Iron is essential for hemoglobin formation and productive erythropoiesis. In
      hemodialysis patients, accurately assessing iron status is a prerequisite for
      diagnosing iron deficiency, monitoring the response to iron supplementation, and
      maintaining effective erythropoiesis. Ideal laboratory tests of iron status
      should accurately indicate whether a patient has an excess or deficiency in
      stored iron as well as in iron readily available for erythropoiesis. Serum
      ferritin and transferrin saturation (TSAT) are iron indices recommended by the
      K/DOQI guidelines for assessing iron deficiency and iron overload. However, since
      serum ferritin and TSAT are indirect measures of iron status, they can be
      unreliable in hemodialysis patients, particularly in those who are receiving
      recombinant erythropoietin. Relying on inaccurate indices of iron status can lead
      to false interpretations of iron overload or iron deficiency, which may lead to
      the unnecessary discontinuation or overdosing of iron supplementation. Newer
      methods of measuring iron status, such as reticulocyte hemoglobin content (CHr),
      may be less variable and more sensitive and specific than the current iron
      parameters.

PMID- 12224371
TI  - Anemia in CKD: prevalence, diagnosis, and treatment. Case study of the anemic
      patient.
AB  - A point-in-time observational study was conducted in over 1,000 nephrology
      offices between November 1999 and December 2000 to determine the prevalence of
      anemia in patients with chronic kidney disease (CKD). Trends in hemoglobin (Hb)
      and serum creatinine (SCr) levels were assessed among 4,831 evaluable patients to
      determine the relationship between renal function and anemia. Results
      demonstrated that anemia is common in patients with CKD, with progressive
      increases in prevalence and severity as renal function deteriorates. Overall,
      26.3% of these patients had Hb levels below 10 g/dL, 46.7% had Hb levels below 11
      g/dL, and 63.9% had Hb levels below 12 g/dL. Despite the high percent of patients
      with anemia, only 31.3% were being treated for this condition. These data suggest
      that anemia is prevalent and undertreated in patients with CKD. Nephrology nurses
      can be influential in providing proactive management of anemia throughout the
      spectrum of CKD to improve anemia-related outcomes.

PMID- 12224372
TI  - Transitioning an adolescent dialysis patient to adult health care.
AB  - B.H. eventually met the outcome goals and made the transition into an adult
      facility. Throughout the process, the dialysis staff discussed ideas and plans
      for the future with B.H. and encouraged increased self-determination, however,
      the time frame was not adequate to allow each step of the process to be carried
      out. No concerted effort was made on the part of the entire multidisciplinary
      team to enable the patient to make a successful transition. A step-driven
      protocol sensitive to the patient's developmental, cognitive, and social
      situation must be implemented into the standards of care. In this way,
      independence can be fostered at an early stage and continued as the patient
      matures.

PMID- 12224373
TI  - Interventions to promote fistula maturation.

PMID- 12224374
TI  - Antihypertensive medications and renal disease.
AB  - Patients with ESRD are likely to have hypertension as a comorbid condition. The
      management of hypertension must involve nonpharmacologic as well as pharmacologic
      treatment. In most cases, nonpharmacologic treatment, including severe sodium
      restriction, smoking cessation, elimination of alcohol intake, and weight
      reduction, can significantly lower blood pressure in the ESRD patient. If these
      methods remain insufficient, then a variety of pharmacologic treatment options
      exist, with ACE inhibitors and diuretics being the most common medical agents
      employed. Treating hypertension in this patient population, while extremely
      challenging, greatly reduces the risk of developing cardiac disease, thereby,
      reducing the risk of mortality.

PMID- 12224375
TI  - Are we taking the right approach in training our staff?

PMID- 12224376
TI  - Effects of ecabet sodium, an antiulcer drug, on gastric adaptive relaxation in
      isolated guinea-pig stomachs.
AB  - Disturbances in the reservoir function of the stomach may cause epigastric
      fullness or early satiety, which are the main symptoms in patients with
      dysmotility-like functional dyspepsia. Gastric adaptive relaxation is involved in
      the reservoir function of the proximal stomach. Ecabet sodium, synthesized from
      abietic acid, is widely used in Japan as an antiulcer drug. The purpose of this
      study was to evaluate the effects of ecabet on gastric adaptive relaxation in
      isolated guinea-pig stomachs. Changes in intragastric volume and pressure were
      recorded in the presence of atropine and guanethidine. Gastric adaptive
      relaxation was triggered by luminal distention. Ecabet at the dose of 20 mmol/l
      in solutions at two pHs (pH 3.0 and 7.4) significantly lowered the threshold
      pressure needed for such relaxation and increased intragastric volume, but lower
      doses had little or no effect. The results suggested that this antiulcer drug
      might improve symptoms in patients with dysmotility-like functional dyspepsia.

PMID- 12224377
TI  - Control of acute pain after major abdominal surgery in 585 patients given
      tramadol and ketorolac by intravenous infusion.
AB  - The aim of this study was to assess the efficacy and safety of postoperative pain
      relief using tramadol and ketorolac in continuous intravenous infusion. The 585
      patients included in the study underwent major surgery according to a protocol
      involving the parenteral administration of 100 mg tramadol approximately 40 min
      before the end of surgery. This was followed by the continuous intravenous
      infusion of 600 mg tramadol and 180 mg ketorolac diluted with physiological
      solution to a total volume of 96 ml. Delivery was carried out using an
      elastomeric pump or a syringe pump and administered over a 48-hour period at a
      constant rate of 2 ml/h. Any further doses consisted of 100 mg tramadol up to a
      maximum of 300 mg over a 24-h period. Pain was assessed on a verbal numeric scale
      (VNS). For each patient the intensity of pain was assessed both at rest and on
      movement (coughing, deep breathing, movement of lower limbs). At the scheduled
      times (T0-T72, every 6 h), the following parameters were evaluated: hemodynamic
      stability; respiratory function; the appearance of any side effects; the level of
      sedation; and the need for any further doses of analgesic. The analysis of the
      data obtained showed the good quality of postoperative pain relief achieved: pain
      intensity at rest was, on average, always below VNS level 3, while during
      movement it always had an average VNS level of 3-4. The only side effects found
      with any frequency were nausea (22.6%) and vomiting (8.5%); hemodynamic and
      respiratory parameters remained stable. The method adopted was of limited cost
      and was well accepted by both patients and staff. On the basis of the data
      obtained, it is possible to affirm that the post-operative pain protocol proposed
      is effective, safe, without significant side effects, and of limited cost.
      Therefore, it is the first choice protocol for our operating unit after major
      abdominal surgery.

PMID- 12224378
TI  - Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and
      cardiovascular diseases: studies in atherosclerotic mice and in humans.
AB  - The beneficial health effects attributed to the consumption of fruit and
      vegetables are related, at least in part, to their antioxidant activity. Of
      special interest is the inverse relationship between the intake of dietary
      nutrients rich in polyphenols and cardiovascular diseases. This effect is
      attributed to polyphenols' ability to inhibit low-density lipoprotein (LDL)
      oxidation, macrophage foam cell formation and atherosclerosis. Pomegranate
      polyphenols can protect LDL against cell-mediated oxidation via two pathways,
      including either direct interaction of the polyphenols with the lipoprotein
      and/or an indirect effect through accumulation of polyphenols in arterial
      macrophages. Pomegranate polyphenols were shown to reduce the capacity of
      macrophages to oxidatively modify LDL, due to their interaction with LDL to
      inhibit its oxidation by scavenging reactive oxygen species and reactive nitrogen
      species and also due to accumulation of polyphenols in arterial macrophages;
      hence, the inhibition of macrophage lipid peroxidation and the formation of lipid
      peroxide-rich macrophages. Furthermore, pomegranate polyphenols increase serum
      paraoxonase activity, resulting in the hydrolysis of lipid peroxides in oxidized
      lipoproteins and in atherosclerotic lesions. These antioxidative and
      antiatherogenic effects of pomegranate polyphenols were demonstrated in vitro, as
      well as in vivo in humans and in atherosclerotic apolipoprotein E deficient mice.
      Dietary supplementation of polyphenol-rich pomegranate juice to atherosclerotic
      mice significantly inhibited the development of atherosclerotic lesions and this
      may be attributed to the protection of LDL against oxidation.

PMID- 12224379
TI  - Neuroprotective properties of a synthetic docosanoid, unoprostone isopropyl:
      clinical benefits in the treatment of glaucoma.
AB  - The characteristic loss of visual field due to glaucoma is directly associated
      with retinal ganglion cell (RGC) death. The process of RGC death is thought to be
      biphasic, starting with a primary injury, followed by a slow secondary
      degeneration. Retinal ischemia may establish the cellular conditions that create
      a fatal biochemical cascade; hypoxia, followed by high excitotoxic levels of
      glutamate cause pathologically elevated levels of intracellular calcium resulting
      in neuronal cell death via apoptosis or necrosis. Impaired ocular perfusion,
      primarily due to abnormal autoregulation and/or vasoconstriction caused by
      endothelin-1, probably contributes to the ischemic milieu. Neuroprotection, the
      preservation of neurons that were either not damaged or only slightly damaged
      during the primary insult, has become important for the clinician when
      considering treatment options. Unoprostone, the first synthetic docosanoid, has
      been demonstrated to exhibit neuroprotective properties. In an ischemic animal
      model, unoprostone protected RGCs in a dose-dependent manner. Unoprostone
      inhibits glutamate stimulation and opens maxi-K channels, which are potassium
      channels that reach an activation threshold only during depolarization and/or at
      high intracellular Ca2+ concentrations. The resultant large efflux of K+
      hyperpolarizes the cell, thereby closing voltage-gated Ca2+ channels and limiting
      neuronal damage by decreasing influx of intracellular Ca2+. Unoprostone has also
      been shown to protect rat photoreceptors from constant light-induced damage.
      Lastly, unoprostone has vasorelaxant properties, evidenced by increased choroidal
      blood flow and inhibition of vasoconstrictors such as endothelin-1. These
      findings indicate that a substantial clinical benefit of unoprostone is
      neuroprotection of RGCs.

PMID- 12224380
TI  - The combination of the SH metabolite of erdosteine (a mucoactive drug) and
      ciprofloxacin increases the inhibition of bacterial adhesiveness achieved by
      ciprofloxacin alone.
AB  - Exposure to ciprofloxacin and other fluoroquinolone antibiotics at less than
      minimum inhibitory concentrations (MICs) reduces the production of some of the
      factors that contribute to bacterial virulence, particularly bacterial
      adhesiveness. Once metabolized, erdosteine (a mucoactive drug) produces an active
      metabolite (Met I) with a reducing sulfhydryl group that is capable of opening
      the disulfide bonds present in tracheobronchial mucins and pilins, a protein of
      bacterial fimbriae (adhesins). This induces stereoconformational changes that
      interfere with the binding of bacterial adhesins to the receptors on mucosal
      cells. The combination of 5 and 10 micrograms/ml of Met I and 1/4, 1/8, 1/16 MICs
      of ciprofloxacin potentiated the inhibition of Staphylococcus aureus and
      Escherichia coli adhesiveness to human mucosal cells in comparison with
      ciprofloxacin alone. This finding opens up an interesting new possibility for
      interfering with bacterial adhesiveness and the resulting virulence by combining
      antibiotics with agents devoid of antibacterial activity.

PMID- 12224381
TI  - Inhibitory effects of N-(substituted benzoylamino)-4-ethyl-1,2,3,6
      tetrahydropyridines on nitric oxide generation in stimulated raw 264.7
      macrophages.
AB  - There has been great interest in reactive nitrogen intermediates and nitric oxide
      production in macrophages, particularly because of their contributory role in
      several pathophysiological conditions during acute and chronic inflammation.
      Several N-(substituted benzoylamino)-4-ethyl-1,2,3,6-tetrahydropyridines were
      previously synthesized as potential antiinflammatory agents. In the present
      study, the effects of four previously synthesized tetrahydropyridines (THPs) on
      cyclooxygenase (COX)-1 and COX-2 were screened and the effects of these compounds
      on lipopolysaccharide (LPS)-induced (2 micrograms/ml) nitric oxide and inducible
      nitric oxide synthase (iNOS) activity in RAW 264.7 macrophages were examined. 4
      Bromo THP showed 9.4 microM of IC50 as the most potent derivative among the
      tested THPs followed by 4-nbuthyl, 4-fuoro, and 4-methyl THP with IC50 values of
      30.9, 38.9 and 80.3 microM, respectively (indomethacin IC50 = 53.8 microM). None
      of the tested compounds showed cytotoxic effects to the RAW 264.7 macrophages.
      All of the tested THPs exhibited COX-1 and COX-2 nonselective inhibition. These
      results suggest that previously synthesized THP derivatives may have dual effects
      through inhibiting both COX and nitric oxide by inhibiting iNOS.

PMID- 12224382
TI  - Isolation of Enterococcus species from infectious skin lesions.
AB  - Enterococcus faecalis was isolated at a frequency of 70% and was chiefly isolated
      from secondary infections due to ulcer/decubitus. Seven sole/predominant E.
      faecalis were isolated. Penicillins were more effective against E. faecalis and
      the sensitivities of E. faecalis to antimicrobials were higher than those of E.
      faecium. Some nonpredominant E. faecalis strains were sensitive to erythromycin
      probably due to less resistant mechanisms. The characterization of Enterococcus
      spp. is especially important when choosing appropriate antimicrobials for
      therapy.

PMID- 12224383
TI  - Brucella spondylitis with paravertebral abscess due to Brucella melitensis
      infection: a case report.
AB  - This report describes the case of a 45-year-old woman with a 5-month history of
      fever, generalized malaise, myalgia, lower back pain and difficulty in walking.
      Serodiagnosis for brucella, carried out at the onset of symptoms 5 months
      previously, was negative. When the patient was admitted to our hospital there was
      contracture of the paraspinal muscles but no peripheral nerve damage. Laboratory
      tests showed positive agglutination for Brucella and an increase in the rate of
      dilution from 1/160 to 1/640 over 2 weeks. Radiographs and a computed tomography
      scan of the spine revealed bone erosion in the posterior borders of the L4-L5
      vertebral end plates and a soft tissue mass surrounding the interposed disc and
      protruding into the spinal canal. Magnetic resonance imaging confirmed the
      presence of a paraspinal abscess around the affected disc and tissue edema.
      Culture tests of the blood and abscess tissue, taken by biopsy, were negative.
      Rifampicin treatment (600 mg daily), combined with a bust cast to immobilize the
      spine, led to clinical healing without the need for surgery. Because onset
      symptoms are nonspecific and insidious, in nonrisk subjects a diagnosis of
      brucellosis may sometimes be suspected only if there are local symptoms. The
      phenomenon of the absence of positivity in patients with a high antibody titer
      should also be considered Cases such as that described herein demonstrate the
      need for culture tests and serodiagnosis, even in nonrisk patients with
      persistent fever and arthralgia, to prevent the later complications of
      brucellosis.

PMID- 12224384
TI  - A multiple-antibiotic resistance-independent active chloramphenicol efflux in an
      Escherichia coli clinical isolate.
AB  - The clinical isolate, Escherichia coli 1941, exhibits high resistance to
      chloramphenicol and tetracycline (minimum inhibitory concentrations of 512
      micrograms/ml). Neither resistance is linked to the large conjugative plasmid
      present in the strain. The intracellular accumulation of radiolabeled
      chloramphenicol increased about 9-fold after the addition of the energy uncoupler
      carbonyl cyanide m-chlorophenol-hydrazone to an E. coli 1941 culture, indicating
      the presence of an active efflux mechanism. Sequence analysis and expression
      study suggested that the multiple-antibiotic resistance marRAB locus and the
      AcrAB drug-efflux pump were not involved in this active efflux of
      chloramphenicol.

PMID- 12224385
TI  - [Mesenteric-portal confluence aneurysm].
AB  - The authors take interest in the portal aneurysm about the observation of a 52
      year-old woman with an echographic lesion in the head of the pancreas.
      Radiological examination was done with abdominal CT and MRI. Because of no
      accurate diagnosis, an explorative laparotomy was done and showed an aneurysm at
      the junction of the portal and superior mesenteric veins. These lesions are rare:
      they can be acquired particularly with underlying hepatocellular diseases and
      portal hypertension; they can be congenital due to an incomplete obliteration of
      the right vitelline vein. If asymptomatic, only a close surveillance must be
      proposed.

PMID- 12224387
TI  - [Effect of pelvic member abduction on the kinematics of the thoracic and lumbar
      spine].
AB  - The motion of thoracic and lumbar spine segments has been analysed by mean of the
      skin landmarks method on 14 volunteers (7 males, 7 females). Results demonstrate
      that: There is no significant difference between male and female. There is either
      facilitation, or limitation of the motion of the characteristic landmarks of the
      spinal segments during trunk motion in perpendicular planes. The mobility of the
      spinal segments is associated with pelvic girdle motion in order to obtain the
      planed amplitude, and varies with hips abduction. The analysis of the precise
      mechanisms of relaxing or stretching of the pelvi-spinal musculo-ligamentous
      structures constitutes a large field of investigation that necessitates the study
      of other pelvic limbs postures and needs the use of robotic techniques.

PMID- 12224386
TI  - [Innervation of Denonvilliers' recto-vesical septum. Anatomic study].
AB  - OBJECTIVE: The retro vesical septum (DENONVILLIERS) can be dissected and
      separated of the prostate and the bladder. The neurovascular bundles bound
      laterally this septum and it must be removed during radial prostatectomy. The aim
      of this study was to know if this septum is crossed by nerves. MATERIAL AND
      METHODS: Dissection of cadaver--histological study of recto-vesical fascia.
      RESULTS: Nerves are present coming from the neurovascular bundle to the septum
      and end in the prostate. CONCLUSION: These anatomical observations conduct to
      recommend to remove systematically the recto-vesical septum during radical
      prostatectomy for cancer.

PMID- 12224388
TI  - [Carabelli's tubercule in the Wolof ethnic group (Senegal)].
AB  - The authors study the Carabelli's trait in a Wolof population (Senegal). This
      morphologiest alteration is mainly present on the first permanent maxillary
      molar. MATERIAL AND METHODS: 195 left and right first molars of 102 individuals
      with one equal sex distribution were used. The morphological examination of 194
      second maxillary molars (left and right) completed the study. RESULTS: They show
      a frequency of 11.8% traits, either individualized (6.7%), either hypertrophic
      (5.1%), with a predominance of attenuated (37.4%) or absent formations (50.8%),
      as well as a sexual dimorphism (19% of individualized or hypertrophic traits in
      the female population, versus 4.2% in the male). The presence of an attenuated
      trait (grooves and pits) on the second molars follows also a repartition in favor
      of the female population (24% versus 4.2%).

PMID- 12224389
TI  - Increase in the number of NADPH-diaphorase-positive neurons in the lumbar dorsal
      root ganglia following lipopolysaccharide exposure of the sciatic nerve.
AB  - In the spinal cord, nitric oxide pathways are involved in hyperalgesia, and
      nitric oxide synthase, the enzyme responsible for its synthesis, is upregulated
      following several noxious and lesion stimuli. Since the histochemical reaction
      for NADPH-diaphorase colocalizes with NOS, we decided to study the effects of
      infusion of bacterial lipopolysaccharides close to the sciatic nerve on the
      expression of NADPH-d in the dorsal root ganglia and spinal cord of the rat. The
      percentage of NADPH-d-positive neurons in the L4 dorsal root ganglia increased 7
      10 times on the treated side of LPS-treated rats (12.5-17.5%, compared to 0.5
      2.5% of control side), whereas sham operation had no effects. The cross-sectional
      area of NADPH-d-positive neuronal profiles in all the dorsal root ganglia
      considered was consistently smaller than that of those which were negative to the
      histochemical reaction. In animals treated with LPS the NADPH-d-positive neurons
      were significantly (p = 0.02) smaller on the treated side (520 +/- 100 microns)
      than on the control one (679 +/- 135 microns), whereas those which were negative
      were of similar sizes on the two sides (1170 +/- 256 microns on the treated side
      vs 1214 +/- 371 microns on the control side). On the contrary, in control
      animals, there were no differences between untreated and sham operated sides, but
      differences between the sizes of NADPH-d-positive and negative neurons persisted.
      Therefore, LPS treatment on the sciatic nerve upregulates NADPH-d expression in
      the corresponding dorsal root ganglion, thus indicating an increased rate of NO
      production. Moreover, NADPH-d is upregulated mainly in small sized neurons, thus
      suggesting that it may be related with pain transmission.

PMID- 12224390
TI  - [Anatomical variations of the brachial plexus].
AB  - Important variations exist in the brachial plexus (Kaufmann, Cunningham, Kerr,
      Lee). Perivascular techniques of brachial plexus block used sometimes use
      important quantities of anaesthesia product. It seems that certain surgical
      treatment failures of brachial plexus lesions are related to the brachial plexus
      variations (Bonnel). Our aim is to study the brachial plexus variations and its
      relations from the cervical region to brachial region. We dissected twenty-three
      brachial plexus (13 women and 10 men, fresh or injected by formalin). We studied
      the brachial plexus anatomic variations and its relations. We found the anatomic
      variations at the level of different parts of brachial plexus: Trunk: 8 cases
      (34.8%); Terminal branch: 8 cases (34.8%); brachial plexus tract: 1 case (4.3%);
      collateral branch: 1 case (4.3%); in 5 cases we didn't find any abnormalities.
      Some studies show the frequency of 4th cervical root (C4) participation in
      brachial plexus. Kerr found 65.9%. It was 30.4% of C4 participation in brachial
      plexus in our series. Among the 8 cases of terminal branch variations in our
      series, two (8.7%) musculocutaneous was low source. The brachial plexus
      variations could fail the brachial plexus loco-regional anaesthesia. In the
      surgical treatment of brachial plexus lesions, the surgeon must know brachial
      plexus anatomical variations perfectly.

PMID- 12224391
TI  - A variant of the Cannieu-Riche communication: case report.
AB  - A variant of Cannieu-Riche communication was encountered during the dissection
      studies. The communication was between the digital branch to the index finger and
      branch to the adductor pollicis muscle. Terminal communications between motor
      nerves may provide muscles with double motor innervation, and are important for
      the motor innervation of the hand, in particular the thenar muscles. This variant
      should be kept in mind during surgical operations, electrophysiological
      examinations of the hand.

PMID- 12224392
TI  - [Recent contributions to the establishment of the axes of the mammalian embryo].
AB  - The study of the establishment of embryonic axes during early development has
      shown that this process is a very early event (occurRing either during ovogenesis
      or during fertilization) for invertebrates and for lower vertebrates. In mammals,
      it was considered that this establishment appears late during development because
      of the great plasticity of blastomeres. Recent data in the mouse embryon show
      that the mammalian ovocyte is a polarized cell, the polar body corresponding to
      the animal pole of this cell. The blastomeres that are generated by the zygote
      divide asynchronously. The first that divides is the one which inherits the
      plasma cell membrane where fertilization takes place. This blastomere will
      preferentially give rise to the cells of the embryonic pole of the blastocyst
      whereas the other yields the cells of the abembryonic pole. The mammalian ovocyte
      is thus a polarized cell with an already established animal-vegetal axis. The
      point of sperm entry will determine the embryonic-abembryonic axis.

PMID- 12224393
TI  - Sequential expression of genes involved in muscular dystrophies during human
      development.
AB  - To elucidate the normal and pathophysiological roles of genes involved in the
      aetiology of muscular dystrophies, we studied the expression of dystrophin, four
      sarcoglycans, beta-dystroglycan and merosin during early human development. These
      proteins are expressed mainly in skeletal muscles while dystrophin, beta
      dystroglycan, delta-sarcoglycan and merosin are in cardiac and smooth muscles.
      Dystrophin, beta-, delta-sarcoglycan and beta-dystroglycan are first expressed in
      the myotome at the 4th week of human embryogenesis, followed by gamma-sarcoglycan
      and merosin at the 6th week of development; alpha-sarcoglycan appears only at the
      level of the muscular fibre at the end of the embryonic period.

PMID- 12224394
TI  - The battle over butts. If the Big Apple bans smoking, who will be next?

PMID- 12224395
TI  - Nasty infections.

PMID- 12224396
TI  - Deadbeat profiteers.

PMID- 12224397
TI  - Cracking the fat riddle.

PMID- 12224398
TI  - When the young take their lives.

PMID- 12224399
TI  - [Nuclear medicine 2001 and "Guidelines for use of radioactivity in medicine":
      consequences for nuclear medicine].

PMID- 12224400
TI  - [Scientific publishing in the journal Nuclear Medicine].
AB  - AIM: The paper reviews current scientific publishing practice in the journal
      Nuklearmedizin. METHOD: The scientific publications in the 2000 and 2001 issues
      of the journal were analyzed retrospectively with regard to their authors, formal
      content criteria and citation practice. RESULTS: 102 articles (69 original
      papers, 29 case reports, 4 review articles) were published. Of a total of 561
      authors, 80 first authors came from Germany, 9 from Austria, 3 from Switzerland,
      and 10 from other countries. In 58 out of the 102 publications, researchers from
      other medical specialties were co-authors. The first authors were based at
      university hospitals or research centers in the case of 88 out of 102
      publications. The author of one article had his own practice. Of the 102 first
      authors, 24 were female with a statistically significantly (p = 0.04) higher
      proportion in case reports compared to original papers. A total of 88/98 original
      papers and case reports were categorized as clinical research, 2 out of 69
      original papers as experimental research, and 8 as management, health policy and
      radiation protection. 36 out of 102 articles were in English. The 69 original
      papers included a median of 48 investigated patients (range 4-991). A total of
      2555 other papers with a median of 19 (range 3-230) was cited, comprising 212
      citations of the journal Nuklearmedizin, i.e. 8.3% (range 0-56%). CONCLUSION: The
      number of authors per paper documents the tendency to team work with a major
      participation of other specialties; university hospitals and research centers are
      represented more often. There is a predominance of clinical research with a high
      average number of patients per study. The percentage of first female authors are
      proportionate to their percentage membership in the learned societies. The
      relatively high percentage of papers in English raises the potential to increase
      the scientific response to publication of the content.

PMID- 12224401
TI  - Early change of thyroid hormone concentration after 131I treatment in patients
      with solitary toxic adenoma.
AB  - AIM: In spite of extensive use of 131I for treatment of hyperthyroidism, the
      results of early outcome are variable. In our prospective clinical study we
      tested whether 131I induced necrosis causing clinical aggravation of
      hyperthyroidism and increasing the free thyroid hormone concentration in the
      serum of patients with solitary toxic adenoma not pretreated with antithyroid
      drugs. PATIENTS AND METHODS: 30 consecutive patients were treated with 925 MBq
      131I. Serum concentration of thyrotropin (TSH), free thyroxine (fT4), free
      triiodothyronine (fT3), thyroglobulin (Tg), and interleukin-6 (IL-6) were
      measured before and after application of 131I. RESULTS: After application of 131I
      no clinical worsening was observed. FT4 and fT3 concentration did not change
      significantly within the first five days, whereas both of them significantly
      decreased after 12 days (p < 0.0001). Slight and clinically irrelevant increase
      in the level of the two thyroid hormones was observed in 9 patients. Furthermore,
      we observed a prolonged increase in Tg concentration and a transient increase in
      IL-6 concentration. CONCLUSION: Neither evidence of any clinical aggravation of
      hyperthyroidism nor any significant increase in thyroid hormone concentration by
      131I induced necrosis of thyroid cells was found. Therefore, the application of
      131I may be considered as a safe and effective treatment for patients with
      hyperthyroidism due to toxic adenoma.

PMID- 12224402
TI  - [Recovery coefficients for the quantification of the arterial input functions
      from dynamic PET measurements: experimental and theoretical determination].
AB  - AIM: For kinetic modelling of dynamic PET data, the arterial input function can
      be determined directly from the PET scans if a large artery is visualized on the
      images. It was the purpose of this study to experimentally and theoretically
      determine recovery coefficients for cylinders as a function of the diameter and
      level of background activity. METHODS: The measurements were performed using a
      phantom with seven cylinder inserts (O = 5-46 mm). The cylinders were filled with
      an aqueous 68Ga solution while the main chamber was filled with a 18F solution in
      order to obtain a varying concentration ratio between the cylinders and the
      background due to the different isotope half lives. After iterative image
      reconstruction, the activity concentrations were measured in the center of the
      cylinders and the recovery coefficients were calculated as a function of the
      diameter and the background activity. Based on the imaging properties of the PET
      system, we also developed a model for the quantitative assessment of recovery
      coefficients. RESULTS: The functional dependence of the measured recovery data
      from the cylinder diameter and the concentration ratio is well described by our
      model. For dynamic PET measurements, the recovery correction must take into
      account the decreasing concentration ratio between the blood vessel and the
      surrounding tissue. Under the realized measurement and data analysis conditions,
      a recovery correction is required for vessels with a diameter of up to 25 mm.
      CONCLUSIONS: Based on the experimentally verified model, the activity
      concentration in large arteries can be calculated from the measured activity
      concentration in the blood vessel and the background activity. The presented
      approach offers the possibility to determine the arterial input function for
      pharmacokinetic PET studies non-invasively from large arteries (especially the
      aorta).

PMID- 12224403
TI  - I-123-lodo-alpha-methyl tyrosine SPECT in non-parenchymal brain tumours.
AB  - PURPOSE: Scintigraphy using I-123-iodo-alpha-methyl tyrosine (IMT) is useful in
      the preoperative characterization of gliomas, in detecting recurrent glioma and
      in the biological re-evaluation of residual or recurrent tumours. A systematic
      evaluation of non-parenchymal brain tumours has not yet been performed. The aim
      of the present study was to evaluate IMT SPECT in the management of intracerebral
      metastases and lymphomas. PATIENTS AND METHODS: IMT uptake was analyzed in 31
      patients with 28 metastases of extracerebral solid tumours and 7 cerebral
      lymphomas. Histology revealed high grade lymphomas, melanomas, and carcinomas of
      the following origin: lung, unknown primary, breast, colon, renal cell, ovary,
      vagina, frontal sinus. IMT uptake was quantified as ratio between maximal tumour
      accumulation and average uptake in the contralateral hemisphere. RESULTS: All
      tumours except two renal cell and one small cell lung carcinoma metastases
      accumulated IMT (91%). The highest IMT uptake was found in a metastasis of lung
      carcinoma. IMT uptake was highly variable and was similar in primary and in
      recurrent tumours. CONCLUSION: Significant accumulation of IMT is seen in the
      majority of tumours, so that this technique might be helpful for the management
      of cerebral metastases and lymphomas.

PMID- 12224404
TI  - Distribution of 5HT2A receptors in the human brain: comparison of data in vivo
      and post mortem.
AB  - AIM: The study presented here firstly compares the distribution of the binding
      potential of the serotonin-5HT2A receptor as measured in vivo with data of
      receptor density taken from literature. Secondly, the sensitivity of the method
      to detect gradual differences in receptor densities is evaluated. METHODS:
      Positron emission tomography (PET) studies were carried out in 6 healthy
      volunteers using the selective serotonin-5HT2A ligand 18F-altanserin. The binding
      potential was quantified in 12 regions using Logan's graphical method and the
      equilibrium method. These data were compared to the distribution of receptor
      density as taken from literature. RESULTS: The binding data in vivo correlated to
      autoradiography data (post mortem) with r = 0.83 (Pearson regression coefficient;
      p < 0.0001). A difference in the receptor density between two regions could be
      detected with p < 0.05 when it amounted at least to 18%. CONCLUSION: This study
      demonstrates a good agreement between in vivo data obtained with 18F-altanserin
      and PET in healthy volunteers and the true autoradiographically determined
      distribution of 5HT2A receptors in human brains. The in vivo method seems to be
      sensitive enough to detect changes in receptor density of more than 18%.

PMID- 12224405
TI  - Ormond's disease: appearance in [F-18]FDG PET imaging.

PMID- 12224406
TI  - [Second generation pioneer of nuclear medicine: Professor (Doctor) Claus
      Schneider].

PMID- 12224407
TI  - [Highlights of the 40th anniversary of the German Society of Nuclear Medicine in
      Frreiburg].

PMID- 12224408
TI  - Infant mortality statistics from the 2000 period linked birth/infant death data
      set.
AB  - OBJECTIVES: This report presents the 2000 period infant mortality statistics from
      the linked birth/infant death data set (linked file) by a variety of maternal and
      infant characteristics. METHODS: Descriptive tabulations of data are presented
      and interpreted. RESULTS: Infant mortality rates ranged from 3.5 per 1,000 live
      births for Chinese mothers to 13.5 for black mothers. Among Hispanics, rates
      ranged from 4.5 for Cuban mothers to 8.2 for Puerto Rican mothers. Infant
      mortality rates were higher for those infants whose mothers had no prenatal care,
      were teenagers, had 9-11 years of education, were unmarried, or smoked during
      pregnancy. Infant mortality was also higher for male infants, multiple births,
      and infants born preterm or at low birthweight. The three leading causes of
      infant death--Congenital malformations, low birthweight, and Sudden infant death
      syndrome (SIDS)--taken together accounted for 45 percent of all infant deaths in
      the United States in 2000. Cause-specific mortality rates varied considerably by
      race and Hispanic origin. For infants of black mothers, the infant mortality rate
      for low birthweight was nearly four times that for white mothers. For infants of
      black and American Indian mothers, the SIDS rates were 2.4 and 2.3 times that for
      non-Hispanic white mothers.

PMID- 12224409
TI  - [Partial androgen deficiency in the aging male: diagnosis and therapy].
AB  - After the fourth decade, androgen serum level fall while the binding capacity for
      testosterone, the sex hormone binding globulin, raises. Clinical symptoms and
      hypogonadism define the syndrome of the partial androgen deficiency of the aging
      male (PADAM). Testosterone substitution may be performed by intramuscular
      injections, oral or transdermal testosterone application. Each patient should
      undergo urological evaluation before starting a testosterone replacement therapy.
      Life style drugs should not be used according the currently rational data. Well
      balanced nutrition, physical training and an active social and sexual life are
      important factors to achieve a healthy aging.

PMID- 12224410
TI  - [Assessment and sex counseling in libido disorders].
AB  - Individual problems, difficulties in the partnership, handicaps of the body and
      the influence of society contribute to sexual problems. In this article a
      definition of hypoactive sexual desire disorders (HSDD) is given. Then the author
      tries to show the many different reasons of disturbed sexual desire to help to
      see the problem from different points of view. Often it is very important for the
      patients to understand why they are unable to feel sexual wishes. In clarifying
      the personal reasons change begins and the couple can find out which next steps
      may be useful to solve the problem of not wanting to want.

PMID- 12224411
TI  - [Curriculum and structure of modern medical education].
AB  - The Medical Faculty of the University of Zurich compiles a fundamental
      restructuring of the Medical curriculum. Basic conditions represent the new Swiss
      Federal law for the education in medical professions (MedBG), heterogeneous
      implementation stages of curriculum reforms of other Swiss Medical Faculties of
      the medicine as well as efforts to improve mobility of students. The strategy of
      the curriculum reform is represented based on the principles decided by the
      Faculty. The authors demonstrate the corresponding organizational structures and
      give a future view focusing on aspects of the implementation and the dynamic
      adaptation of curriculum items.

PMID- 12224412
TI  - [Continuing education and quality assurance].
AB  - The goal of Continuous medical education is to increase knowledge and skills of
      medical doctors to guarantee a high standard of medical care. According to the
      published literature on the effect of Continuous medical education interactive
      didactic methods seems to be more effective to reach the mentioned goal compared
      to lectures. These results are in accordance with the constructivist learning
      theory. The assessment of the learning needs, one of the fundamental elements of
      this theory, is a complex issue. A potential method to evaluate the needs is
      presented in the following paper.

PMID- 12224413
TI  - [Role of radiotherapy in non-small cell lung cancer].
AB  - Lung cancer has the highest cancer mortality in Switzerland. 80% of all lung
      cancer patients are patients with non-small cell lung cancer. Despite advances in
      the pre-treatment evaluation and treatment strategies, cure for non-small cell
      lung cancer ist still rare. Multimodality approaches specifically for locally
      advanced non-small cell lung cancer are among the most promising strategies to
      improve long term tumour control. In this paper we discuss the role of radical
      primary and adjuvant radiotherapy for a stage one to four non-small cell lung
      cancer.

PMID- 12224415
TI  - Double freezing of cod fillets: influence on sensory, physical and chemical
      attributes of battered and breaded fillet portions.
AB  - Fillet samples were processed on board a research vessel from cod (Gadus morhua)
      in different states of rigor mortis. In addition, headed and gutted fish in
      different states of rigor were frozen and, after ten days of frozen storage, the
      fish were thawed, processed into fillets and refrozen. During subsequent frozen
      storage at -24 degrees C of breaded and battered portions processed from the
      different fillet batches several quality attributes were tested using sensory,
      physical, and chemical methods. The measurements indicated differences in the
      quality attributes depending on refreezing and rigor states. Especially the
      sensory texture attributes gumminess and, with some restrictions, firmness were
      found to be suitable for distinguishing single frozen (SF) from double frozen
      (DF) samples. This finding was supported by the outcome of the measurement of
      penetration force where generally a significantly (p < 0.05) higher force was
      necessary to penetrate the DF compared to SF samples. DF samples were generally
      lighter (higher L*) than SF samples. The colour difference delta E between both
      sample types was at least very clear and therefore visible. However, no clear
      differences between SF and DF samples were found when evaluating the flavour
      attributes and using instrumental texture profile analysis for texture
      characterisation. Also, all chemical parameters measured did not allow to clearly
      distinguish between single and double frozen samples. Therefore, it can be stated
      that, at least when using cod as raw material for processing battered and breaded
      portions, the different methods for preparing the fillet blocks will, if at all,
      only affect the textural quality of the final products.

PMID- 12224414
TI  - Effect of ice storage on the functional properties of proteins from shark
      (Scoliodon laticaudus) meat.
AB  - Ice storage characteristics of Scoliodon laticaudus with reference to
      physicochemical and functional properties have been assessed. Total nitrogen
      content reduced to a value of 3.90 g/100 g from an initial value of 4.27 g/100 g
      of meat. Moisture content did not show much variation. The initial nonprotein
      nitrogen content which was 1.09% w/w of meat reduced to 0.98% during ice storage.
      Urea content of shark meat reduced by 25% during 12 days of ice storage. The
      increase in total volatile base nitrogen of shark meat was more than twofold at
      the end of 12 days of ice storage. Solubility of proteins showed an initial
      increase reaching a value of 87.9%, further reduced with ice storage. Gel
      filtration profile and SDS-PAGE pattern indicated aggregation of protein
      fractions and also showed dissociation or cleavage to small molecular weight
      fractions. Slope of reduced viscosity curve as a function of protein
      concentration decreased with ice storage period. Emulsion capacity of proteins
      from shark meat reduced from a value of 0.18 mL oil/mg protein to 0.14 mL oil/mg
      protein after 12 days of ice storage. Gel forming ability of shark meat monitored
      by dynamic viscoelastic measurement, gel strength, expressible water content and
      folding test showed that shark meat has got excellent ability to form gel and
      this property was marginally reduced during ice storage.

PMID- 12224416
TI  - Effect of freezing and canning on the content of selected vitamins and pigments
      in seeds of two grass pea (Lathyrus sativus L.) cultivars at the not fully mature
      stage.
AB  - Seeds of the grass pea (Lathyrus sativus L.) cultivars Derek and Krab, with a dry
      matter content of about 33%, were used for freezing and for canning. The content
      of vitamins C, B1, and B2 and of carotenoids, beta-carotene, and chlorophylls was
      determined in raw and blanched material, in frozen products after 6-month storage
      before and after cooking to consumption consistency, and in canned products after
      6-month storage. In comparison with the cultivar Krab, raw seeds of Derek
      contained 45% more vitamin C, 14% more total chlorophylls, 13% less thiamine
      (vitamin B1), and 7% less riboflavin (vitamin B2). The level of carotenoids was
      similar. Blanching of seeds led to a statistically significant decrease only in
      the content of vitamin C. Freezing and frozen storage significantly lowered the
      level of vitamin C and chlorophylls. The cooking of frozen seeds and the
      production of canned products and their storage resulted in a statistically
      verified reduction in the content of components analysed in all the samples.
      Greater losses were found in products prepared from seeds of the cv. Krab. After
      cooking, frozen seeds contained more of all the analysed components than the
      canned products.

PMID- 12224417
TI  - Infrared analysis of Macedonian mushroom dietary fibre.
AB  - The existing confusion in the terminology and composition of the mushroom dietary
      fibre literature data induced us to analyze simultaneously the chemical
      constitution of various dietary fibre isolates obtained from numerous mushroom
      samples. For that purpose, in 53 kinds of edible Macedonian mushrooms total
      dietary fibre was isolated by two parallel methods intended for material of plant
      and animal origin. With the aid of infrared spectroscopy the chemical
      constitution of the both isolated components was also investigated. The infrared
      spectra of the total dietary fibre isolates, obtained according to both applied
      methods, were similar and close to chitin. In all spectra cellulose is missing.

PMID- 12224418
TI  - Characterization of phospholipid composition of black cumin (Nigella sativa L.)
      seed oil.
AB  - Black cumin (Nigella sativa L.) seed oil was extracted with two different
      solvents, n-hexane (H) and a mixture of chloroform/methanol (CM) (2:1, by
      volume). Amount of total lipid (TL) was higher in the CM miscelle (39.2% of seed
      fresh weight) than in the H extract (37.9%). Chemical characteristics as well as
      fatty acid profile of the TL extracts were compared and the analysis revealed
      that the major fatty acid was linoleic acid C18:2n-6 (ca. 57% of total fatty acid
      methyl esters (FAME)) followed by oleic acid C18:1n-9. Palmitic acid C16:0 was
      the major saturated fatty acid and detected in appreciable level. Chromatography
      on a silica column with solvent of increasing polarity yielded 96.1-97.2% neutral
      lipids (NL) and ca. 3% of polar lipids. Gas liquid chromatography with flame
      ionization detector (GLC/FID) showed that the major fatty acid present in all
      lipid classes was C18:2n-6 followed by C18:1n-9 and C16:0 acids, respectively.
      Phospholipid (PL) classes were separated via normal-phase HPLC. Separation was
      achieved on a silica column by gradient elution from isooctane/2-propanol (6:8,
      by volume) to isooctane/2-propanol/water (6:8:0.6, by volume) lasting 35 min with
      UV detection at 205 nm. The major individual PL classes were found to be
      phosphatidylcholine (PC; ca. 46-48% of total PL) followed by
      phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylinositol
      (PI), respectively. Phosphatidylglycerol (PG), lysophosphatidylethanolamine (LPE)
      and lysophosphatidylcholine (LPC) were isolated in smaller quantities. The level
      of saturated fatty acids, namely palmitic C16:0 and stearic C18:0 acids, was
      considerably higher in PL classes than in the corresponding triacylglycerols.
      Characterization of PL profile from Nigella sativa L. seed oil as well as the
      development of new source of PL was the primary aim of this study.

PMID- 12224419
TI  - Effect of macerate enzymes on the yield, quality, volatile compounds and
      rheological property of prickly pear juice.
AB  - Pectinase and cellulase enzymes were used to investigate efficacy for improving
      juice yield, stability and quality from prickly pear fruit. Pectinase improved
      the yield, stable color, color-assayed as release of anthocyanins or carotinoids
      and clarity of the juice. A significant increase in the effectiveness of
      pectinase was observed as the concentration was increased from 0.05 to 0.50% v/w.
      However, at concentration > 0.25% v/w they tended to impart a bitter flavor in
      the juice. Among three concentrations of pectinase and cellulase, pectinase at
      0.50% v/w produced higher yield, a sediment-free clear juice and high-quality
      juice. The results indicated that depectinated clarified prickly pear juice
      behaves as a Newtonian fluid. It was found that the activation energy (Ea) for
      viscous flow was in the range of 5.02 x 10(3)-20.06 x 10(3) kJ/mol depending on
      the concentrations of pectinase and cellulase enzyme treatment of prickly pear
      juice, in contrast to 22.15 x 10(3) kJ/mol in untreated juice. Volatile compound
      concentrations of twelve compounds were not affected by pectinase and cellulase
      treatment. Overall the quality of prickly pear juice was better in pectinase
      treated juice compared with untreated and cellulase-treated juice.

PMID- 12224420
TI  - Utilization of Lactobacillus sp. for steroid glycoalkaloids degradation by lactic
      acid fermentation.
AB  - The degradation fo steroid glycoalkaloids (SGAs) has been studied in model
      solutions. The number of colony forming units (CFU) was determined using a
      nondirect (cultivation) method during all stages of fermentation. The changes in
      SGAs content were observed by HPLC on the Supelcosil LC-NH2 column. The changes
      in alpha-tomatine concentration added to fermented Lactobacillus MRS broth have
      been studied. A mathematical model of steroid glycoalkaloids degradation during
      lactic fermentation was proposed. The mathematical model was based on the
      experimental data of SGA and glucose concentration and should be used for study
      and prediction of SGA concentration changes of fermented samples. The ratio of
      SGA degradation rate by fermentation and by lactic acid hydrolysis was
      calculated. The experimental data evaluated by proposed mathematical model for
      the selected strain of Lactobacillus plantarum 976H show real feasibility for SGA
      degradation by lactic acid fermentation.

PMID- 12224421
TI  - Effect of thiamine hydrochloride, pyridoxine hydrochloride and calcium-d
      pantothenate on the patulin content of apple juice concentrate.
AB  - Thiamine hydrochloride, pyridoxine hydrochloride and calcium-d-pantothenate were
      applied apple juice concentrates (AJC) at various doses in order to reduce the
      patulin content. AJC samples containing high levels of patulin were stored at 22
      +/- 2 degrees C and 4 degrees C for 6 months after vitamins were added. Patulin
      was fully degraded at the end of a 6-month period in samples stored at 22 +/- 2
      degrees C, on the other hand, other quality parameters diminished significantly.
      Without any considerable reduction on other quality parameters, applications of
      1000 and 2500 mg/kg calcium-d-pantothenate resulted in reduction of patulin of
      73.6 and 94.3%, respectively, however, 42.1% of patulin reduction was observed in
      the control sample of AJC stored for 1 month at 22 +/- 2 degrees C. Addition of
      thiamine hydrochloride (1000 mg/kg), pyrodoxine hydrochloride (625 or 875 mg/kg)
      and calcium-d-pantothenate (1000 or 2500 mg/kg) into the samples and storage at 4
      degrees C for 6 months yielded 55.5 to 67.7% of patulin reduction which was only
      35.8% for the control while the other quality parameters were protected
      adequately.

PMID- 12224422
TI  - Controlling organic chemical hazards in food manufacturing: a hazard analysis
      critical control points (HACCP) approach.
AB  - Hazard analysis by critical control points (HACCP) is a systematic approach to
      the identification, assessment and control of hazards. Effective HACCP requires
      the consideration of all hazards, i.e., chemical, microbiological and physical.
      However, to-date most 'in-place' HACCP procedures have tended to focus on the
      control of microbiological and physical food hazards. In general, the chemical
      component of HACCP procedures is either ignored or limited to applied chemicals,
      e.g., food additives and pesticides. In this paper we discuss the application of
      HACCP to a broader range of chemical hazards, using organic chemical contaminants
      as examples, and the problems that are likely to arise in the food manufacturing
      sector. Chemical HACCP procedures are likely to result in many of the advantages
      previously identified for microbiological HACCP procedures: more effective,
      efficient and economical than conventional end-point-testing methods. However,
      the high costs of analytical monitoring of chemical contaminants and a limited
      understanding of formulation and process optimisation as means of controlling
      chemical contamination of foods are likely to prevent chemical HACCP becoming as
      effective as microbiological HACCP.

PMID- 12224423
TI  - Effect of addition of grit made of crude and expanded amaranth seeds on the
      quality of canned meat.
AB  - Grit made of crude and expanded amaranth seeds was added to meat-fat batter in
      order to determine its effect on its quality. Amaranthus cruentus seeds were
      expanded by the nonpressure method and graded by density (degree of expansion)
      into three fractions: 341, 208 and 135 kg/m3; crude seed density was 800 kg/m3.
      Then the seeds were ground to a homogeneous mass with granulation of 0.8 mm. The
      water-holding capacity and viscosity of grit made of crude and expanded seeds
      were determined. Class II pork was used for the production of meat-fat batter.
      Cooking losses were determined in model meat-fat batter, pasteurized and
      sterilized cans. The texture and color parameters of canned meat were also
      determined, and a taste-panel evaluation was made. It was found that expanded
      seed grit was characterized by worse hydration and gelling properties than crude
      seed grit. Grit made of crude amaranth seeds had a positive effect on the water
      holding capacity of stuffing and allowed to reduce the cooking losses in cans.
      Better water-holding capacity resulted in an improvement in the tenderness,
      juiciness and taste of canned meat. Its quality deteriorated when large amounts
      of highly-expanded seed grit were used.

PMID- 12224424
TI  - The effect of different cooking procedures on microbiological and chemical
      quality characteristics of Tekirdag meatballs.
AB  - In this research, the effects of different cooking processes (grilling, oven, and
      microwave cooking) on microbial flora and chemical composition of the raw and
      cooked meatballs as consumed in Tekirdag were investigated. Microbial flora of
      the raw meatballs was as follows: total bacteria, 6.02 x 10(6) cfu/g;
      psychrophilic bacteria, 1.3 x 10(5) cfu/g; yeast and mould, 2.4 x 10(5) cfu/g;
      coliforms, 1.1 x 10(5) cfu/g; Escherichia coli, 1.0 x 10(2) cfu/g; total
      staphylococcae, 3.3 x 10(2) cfu/g; Staphylococcus aureus, 85 cfu/g. While
      Salmonella was found in only one sample, none of the samples contained
      Clostridium perfringens. The cooking processes clearly decreased the microbial
      flora (2-3 log cycles in grilling (71 degrees C) and oven-cooked (79 degrees C),
      3-4 log cycles in microwave (97 degrees C) heating) of the meatballs. However,
      because of the crust formation and high moisture losses from the meatball surface
      in microwave heating, some sensorial defects were observed in the final product.
      Also, fat and moisture losses were higher in microwave cooking compared to the
      other cooking processes. In conclusion, it is advised to use slightly higher
      temperatures than used in the grilling or conventinal cooking procedures to
      increase microbial quality of the meatballs studied in this research.

PMID- 12224425
TI  - Effect of the roasting method on the content of 5-hydroxytryptamides of
      carboxylic acids in roasted coffee beans.
AB  - Coffee beans of Coffea liberica (robusta) variety were roasted using convection
      and microwave heating. For roasting we used green coffee beans of 7.5% moisture
      content, and beans wetted to 10% moisture content and dried to 5% moisture
      content. The content of 5-hydroxytryptamides of carboxylic acids C-5-HT
      (determined by TLC) as the index of substances irritating alimentary canal was
      investigated in the roasted beans, depending on the bean treatment before
      roasting and applied roasting method. Analytical results show that predrying of
      the coffee beans caused 15-30% loss of C-5-HT, depending on the applied drying
      conditions. The content of C-5-HT in the roasted beans depended on the roasting
      method and preliminary treatment of the beans prior to roasting. A higher C-5-HT
      loss occurred in the case of beans subjected to two-stage processing, predrying
      and roasting. Convection roasting caused higher degradation of C-5-HT than
      microwave roasting.

PMID- 12224426
TI  - Thermal modifications of structure and co-denaturation of alpha-lactalbumin and
      beta-lactoglobulin induce changes of solubility and susceptibility to proteases.
AB  - Study of heat denaturation of major whey proteins (beta-lactoglobulin or alpha
      lactalbumin) either in separated purified forms, or in forms present in fresh
      industrial whey or in recomposed mixture respecting whey proportions, indicated
      significant differences in their denaturation depending on pH, temperature of
      heating, presence or absence of other codenaturation partner, and of existence of
      a previous thermal pretreatment (industrial whey). alpha-Lactalbumin, usually
      resistant to tryptic hydrolysis, aggregated after heating at > or = 85 degrees C.
      After its denaturation, alpha-lactalbumin was susceptible to tryptic hydrolysis
      probably because of exposure of its previously hidden tryptic cleavage sites (Lys
      X and Arg-X bonds). Heating over 85 degrees C of beta-lactoglobulin increased its
      aggregation and exposure of its peptic cleavage sites. The co-denaturation of
      alpha-lactalbumin with beta-lactoglobulin increased their aggregation and
      resulted in complete exposure of beta-lactoglobulin peptic cleavage sites and
      partial unveiling of alpha-lactalbumin tryptic cleavage sites. The exposure of
      alpha-lactalbumin tryptic cleavage sites was slightly enhanced when the alpha
      lactalbumin/beta-lactoglobulin mixture was heated at pH 7.5. Co-denaturation of
      fresh whey by heating at 95 degrees C and pH 4.5 and above produced aggregates
      stabilized mostly by covalent disulfide bonds easily reduced by beta
      mercaptoethanol. The aggregates stabilized by covalent bonds other than disulfide
      arose from a same thermal treatment but performed at pH 3.5. Thermal treatment of
      whey at pH 7.5 considerably enhanced tryptic and peptic hydrolysis of both major
      proteins.

PMID- 12224427
TI  - Antioxidant properties of differently processed spinach products.
AB  - The effect of variously processed spinach products (whole-leaf, minced and
      enzymatically liquefied spinach) on lipid oxidation was determined. In an
      autoxidative methyl linoleate (MeLo) system the inhibition of hydroperoxide
      formation, measured by HPLC after three days of oxidation, was in descending
      order: whole-leaf > liquefied > minced spinach. The inhibition of formation of
      thiobarbituric acid-reactive substances (TBARS) and hexanal by spinach was
      determined in cooked meatballs with added spinach after two days of storage at 4
      degrees C. The formation of TBARS was inhibited by liquefied spinach at 200 g/kg
      meat; all other spinach products tested at 100 and 200 g/kg were pro-oxidative.
      The formation of hexanal was inhibited by both minced and liquefied spinach at
      100 and 200 g/kg meat. The variously processed spinach products behaved
      differently when tested for their antioxidant activity (MeLo) or oxidative
      stability (meatballs). We conclude that the effect of spinach products on lipid
      oxidation is affected by processing.

PMID- 12224428
TI  - Influence of the emulsion components and preparation method on the laboratory
      scale preparation of o/w emulsions containing different types of dispersed phases
      and/or emulsifiers.
AB  - Emulsification is a complex process, strongly influenced by emulsion composition
      as well as by preparation procedure, and the characterisation of emulsions with
      regard to their structure and stability can be carried out with many different
      methods. To evaluate the influences of emulsion composition and preparation
      procedure on the structure and properties, oil-in-water emulsions were prepared
      using the model dispersed phase dodecane and the surfactant Tween on the one hand
      and the real food components sunflower oil (dispersed phase) and casein
      (emulsifier) on the other hand. The emulsions were prepared in a small laboratory
      scale with a turbo-mixer alone and in combination with ultrasonic treatment. The
      emulsion activity was measured by photometry, the emulsion stability was
      evaluated visually and the droplet size was determined by laser particle
      analysis. The results of the investigations made with the model substances agree
      only partly with those made with the real food substances. For the model
      emulsions strong correlation were found between the emulsion activity and the
      particle sizer data because of the high purity and the defined structure of the
      model substances. On the contrary, for the emulsions made with the real food
      components sunflower oil and sodium caseinate the correlation were much weaker.
      Therefore a proper characterisation of the structure and properties of food
      emulsions requires examinations with several methods which are independent from
      each other. Furthermore, for laboratory-scale emulsification the combination of
      turbo-mixer and ultrasonic treatment is suitable to obtain small droplets and a
      narrow droplet distribution also for very small emulsion volumes.

PMID- 12224429
TI  - [Retroperitoneal pathology].
AB  - The retroperitoneum is one of the most complex regions of human anatomy as it
      contains a variety organs and structures from different systems, in particular
      those belonging to the urinary and digestive tracts and the vascular systems. The
      emergence of different diagnostic imaging techniques has made easier to study the
      retroperitoneum. Thanks to ultrasonography, computerised tomography and magnetic
      resonance the assessment of retroperitoneal conditions has taken a great leap
      forwards permitting the anatomical connections and characteristics of the
      structures in this region to be reliably established. Owing to the location in
      the retroperitoneal space of the different organs of the digestive tract and the
      vascular system, a multidisciplinary approach is required involving the different
      surgical specialties. The urologist performs a large proportion of his surgical
      activity in this region and must, therefore, have a good knowledge of the
      different retroperitoneal organs belonging to the urinary tract and also the
      connections between these and other organs and structures of the retroperitoneal
      region.

PMID- 12224430
TI  - [Urinary diversions and bladder enlargements].
AB  - Overall review that offers an integrated insight of the importance and
      repercussions of urinary by-pass and bladder replacement. Over the last decades
      there has been a growing interest in the possibility of reconstructing the
      urinary system and there are now an almost infinite number of surgical solutions.
      The history of the development of using the intestine for by-passes and the
      reconstruction of the urinary system is described. The secondary metabolic
      alterations, the possibility of secondary intestinal tumours and the rudiments of
      ureterointestinal anastomosis are dealt with. Bladder substitution techniques are
      highlighted, and the vast experience of the Urology Department of Hospital Miguel
      Servet explained, including criteria and conclusions that help to choose from the
      many urological surgery alternatives headed by urinary by-pass and bladder
      complications.

PMID- 12224431
TI  - [Treatment of benign prostatic hypertrophy: present situation and future
      prospects].
AB  - Review article offering an up-to-date view and a forecast for the future
      evolution of a disease which over the last few years has been the subject of
      increasingly scientific thoroughness. It deals with the natural history of the
      disease and the application of basic knowledge from other fields. It establishes
      the importance of a therapeutic evaluation of the results obtained with
      alternative medical and surgical approaches in the management of this entity.
      This review of benign prostate hyperplasia analyses the present realities and the
      future perspectives of the disease. It includes the most important contributions
      from international consensus and recommendations, and evaluation of the impact of
      drug treatment, the discredit of alternative options, the contribution of basic
      sciences to the understanding of the development of prostate cancer and the
      future of surgical management (TUR) and its alternatives.

PMID- 12224432
TI  - [Renal injuries: diagnosis and current management].
AB  - Abdominal trauma is relatively frequent and around 5% of the cases correspond to
      renal trauma. At present, a large percentage of cases can be managed
      conservatively. Generalised use of CT and cumulative experience have defined the
      cases that can be treated with good prospects. The currently accepted indications
      for imaging techniques and the most frequent ratings used are described.
      Similarly, the indications for surgical renal examination are listed and the
      principles for renal reconstruction described in the most recent publications of
      the most experienced medical centres.

PMID- 12224433
TI  - [Basic sciences and urology].
AB  - Opinion article offering an up-to-date view and evolutionary prediction of the
      tremendous impact of the gradual but real permeation of the Basic Sciences into
      the field of Urology. The significance of the transition from
      anatomy/knowledge/surgical-technique to pathophysiological knowledge/basic
      science/medical therapy is emphasised. These criteria provide food for thought in
      many areas of urology including vesico-prostatic function, erectile dysfunction
      and, more comprehensively, uro-oncology.

PMID- 12224434
TI  - [Iatrogenic injury of the lumbar ureter and iliac vessels after lumbar
      discectomy: urologic treatment using kidney autotransplantation].
AB  - We report a case of a patient with a secondary injury of external iliac artery
      and vein in the L4-L5 laminectomy and discectomy course. An immediately vein
      suture and ilio-iliac by-pass with Dacron was made. In the postoperative a
      iatrogenic lumbar ureter section was discovered and treated with renal
      autotransplantation. We review the options described in the literature in the
      management of these complex ureteral injuries.

PMID- 12224435
TI  - [Carcinosarcoma of the renal pelvis: report of a case and review of the
      literature].
AB  - Carcinosarcomas arising in the renal pelvis are uncommon neoplasms. All
      previously reported cases are isolated reports and have shown to carry a poor
      prognosis. We report a new case of a 59-year-old man, describing the clinical,
      radiological and histopathological features.

PMID- 12224436
TI  - [Utility of prostate-specific antigen in pleural fluid for the diagnosis of
      metastatic effusion secondary to prostate cancer].
AB  - Pulmonary or pleural involvement from prostate cancer is an uncommon clinical
      finding. We report on a patient with prostate cancer and a diagnosis of malignant
      pleural effusion made by determination of pleural fluid prostate specific
      antigen.

PMID- 12224438
TI  - [Urachal actinomycosis: apropos of a case].
AB  - The report a new case of infected urachal cyst. The embryologic origin of the
      urachus, its anomalies, clinical features, diagnosis and treatment are discussed
      with the case of a 51 years old man who presented an hypogastric mass with the
      diagnosis of urachal actinomycosis.

PMID- 12224437
TI  - [Intra-sinusal renal angiomyolipoma. Differential diagnosis from renal artery
      aneurysm].
AB  - We report a case of atypical renal angiomyolipoma (AML) because of its clinic
      presentation like colic renal pain, its uncommon intrasinusal location, its low
      fatty content, and especially because of the diagnostic doubt with a renal artery
      aneurysm that could not be resolved before the surgery in spite of making Doppler
      ultrasound, renal one sided arteriography, computed tomography (CT) and magnetic
      resonance imaging (MRI). We gave up doing a percutaneous needle biopsy because of
      the location, the association with hematoma and the possibility of a vascular
      origin. It has been said that diagnostic images, mainly ultrasound and CT, have a
      high capacity to get a renal AML diagnosis before the surgery. However when there
      is an atypical characteristics association like we have talked about, dismissing
      other pathologies is necessary. We believe AML must be considered one of these
      because of its difficult differential diagnosis.

PMID- 12224439
TI  - Transforming growth factor-beta 1-induced collagen production in cultures of
      cardiac fibroblasts is the result of the appearance of myofibroblasts.
AB  - Transforming growth factor-beta 1 (TGF-beta 1), which appears in high
      concentrations in fibrotic cardiac tissue, is a potent inductor of tissue
      collagen deposition and of the differentiation of fibroblasts to myofibroblasts.
      It is accepted that TGF-beta 1 is a potent stimulator of collagen secretion by
      fibroblasts. The aim of the present study was to determine which type of cells,
      fibroblasts and/or myofibroblasts are stimulated, in terms of collagen
      production, by TGF-beta 1. Therefore, using cultures of second-passage rat
      cardiac fibroblasts, we investigated the dose- (0.003-15 ng/ml) and time
      dependence (2-48 h) of the TGF-beta 1-induced effects on collagen production and
      on the appearance of myofibroblasts, as estimated by the presence of alpha-smooth
      muscle actin (alpha-SMA; a marker of myofibroblasts). The reversibility of the
      TGF-beta 1-stimulated effects was also studied. The dose- and time-dependent
      stimulation of collagen production was closely associated with the induction of
      alpha-SMA. TGF-beta 1 did not change the cell phenotype or increase collagen
      production in rat cardiac fibroblasts cultures after a long incubation (24-28 h)
      at low concentrations (< 1 ng/ml), or after a short incubation (2-4 h) at high
      concentrations (1-15 ng/ml). However, after a long incubation at high
      concentrations, TGF-beta 1 changed the cell phenotype and increased collagen
      production in these cultures through the differentiation of fibroblasts to
      myofibroblasts. A maximal increase of collagen production (two-fold, p < 0.001)
      was observed after incubation of fibroblasts with 15 ng/ml TGF-beta 1 for 48 h.
      Under these conditions, alpha-SMA was increased by 3.5-fold (p < 0.001) and
      second-passage cultures of fibroblasts and their offspring in the next passage
      consisted mainly of myofibroblasts. The stimulation of collagen by 15 ng/ml TGF
      beta 1 for 48 h was irreversible. In fact, additional incubation of these second
      passage TGF-beta 1-stimulated cultures without TGF-beta 1 for 2 days did not
      decrease the high activity of collagen production. Moreover, the third-passage
      offspring of these TGF-beta 1-stimulated fibroblasts cultured without TGF-beta 1
      also showed a higher production of collagen compared with control fibroblasts.
      Furthermore, the increased collagen production in the third-passage fibroblast
      offspring of the second-passage TGF-beta 1-stimulated fibroblasts could not be
      further stimulated by TGF-beta 1. Thus, the activity of collagen production in
      TGF-beta 1-stimulated cultures and in their next passage offspring is not
      sensitive to TGF-beta 1. Our data suggest that TGF-beta 1-stimulated collagen
      production in cultures of adult rat cardiac ventricular fibroblasts cannot be
      explained by a direct stimulation of collagen production, either in fibroblasts
      or in myofibroblasts. Instead, TGF-beta 1 induces differentiation of fibroblasts
      to myofibroblasts, the latter having a higher activity for collagen production
      than the former.

PMID- 12224440
TI  - Effects of two newly synthesized 4-hydroxycoumarin derivatives (4-OHC) on
      isolated rat hepatocytes.
AB  - To clarify the hepatotoxicity of two newly synthesized derivatives of 4
      hydroxycoumarin (OX and AC) with proven anticoagulant activity in comparison with
      warfarin, we investigated freshly isolated rat hepatocytes. Hepatocyte damage
      after incubation with OX, AC and warfarin at a final concentration of 1 x 10(-8)
      M to 1 x 10(-3) M was assessed by measuring cell viability, lactatdehydrogenase
      (LDH) activity and glutathione (GSH) levels. The results of cell viability
      assessment showed that warfarin had the highest toxicity, followed by OX and AC.
      LDH activity of the tested compounds was mostly increased by warfarin. According
      to the average effective concentration of the compounds on this parameter,
      warfarin possessed the most significant toxic effect (EC50 = 1 x 10(-7) M),
      followed by AC (EC50 = 9.7 x 10(-5) M) and OX (EC50 = 5.0 x 10(-4) M). The
      observed cytotoxic effects were most pronounced in the highest concentration 1 x
      10(-3) M as follows: warfarin, AC and OX. The differences in the effects of OX
      and AC may be explained by the differences in the electronic structure of the
      novel compounds, as assessed by molecular modeling.

PMID- 12224442
TI  - Studies on the antilithic effect of Rotula aquatica lour in male Wistar rats.
AB  - The decoction of Rotula aquatica lour was screened for antilithic activity in
      male Wistar rats and the results were summarized based on the ionic changes in
      both urine and serum. Nephrolithiasis was induced in rats by feeding them 3%
      glycolic acid mixed feed for 45 days, which resulted in high urinary calcium,
      oxalate and high serum potassium. Simultaneous treatment with the decoction
      reduced calcium and oxalate ion concentration in urine, confirming the stone
      inhibitory effect. Histopathological studies of kidney tissue samples further
      substantiated the findings. The decoction was found to be nontoxic over the 45
      day treatment period.

PMID- 12224441
TI  - Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) as a tool for
      differentiation of P2Y2-receptor-mediated vasorelaxation in guinea pig aorta.
AB  - The action of the putative P2Y1-receptor antagonist pyridoxalphosphate-6
      azophenyl-2',4'-disulphonic acid (PPADS) was studied in guinea pig aorta for
      potential use in the differentiation between P2Y1 and P2Y2 purine receptors.
      Concentration-effect curves to 2-methylthioadenosine triphosphate (2MeSATP) and
      uridine triphosphate (UTP), agonists at P2Y1- and P2Y2-receptor sites,
      respectively, and the common agonist adenosine triphosphate (ATP) were
      constructed in guinea pig aortic ring preparations with the tone raised by 5
      microM of noradrenaline. A ranked order of agonist potency of 2MeSATP > ATP > UTP
      resulted from the construction of concentration response curves to vasorelaxation
      of the agonists. Deendothelialization virtually abolished vasorelaxation to UTP
      but made no significant difference to 2MeSATP-induced responses. PPADS exhibited
      noncompetitive inhibition at P2Y1-receptor sites by reducing the maximal response
      to 2MeSATP, although a trend towards a right shift of the concentration-effect
      curves was observed. In total contrast, PPADS enhanced P2Y2-mediated
      vasorelaxation to UTP by shifting the concentration-effect curves to the left and
      increasing maximal responses. Thus, PPADS is a noncompetitive antagonist at P2Y1
      receptors but enhances responses, at least to UTP, at P2Y2 receptors in guinea
      pig aorta via a hitherto unknown mechanism. Thus, PPADS is a potentially useful
      substance that may be used for differentiation between P2Y1 and P2Y2 receptors in
      the guinea pig aorta.

PMID- 12224443
TI  - Methods for assessing endothelin ETA-receptor antagonists in preclinical studies.
AB  - Endothelin-1 (ET-1) has been found to be one of the most potent vasoconstrictive
      peptides known, and is therefore considered to be an important factor in diseases
      such as hypertension, heart failure, pulmonary hypertension, renal diseases, etc.
      Thus, the development of ET-receptor antagonists may offer a new therapeutic
      strategy in these fields. In this article, we summarize the method for assessing
      our compound as a selective ETA-receptor antagonist. Binding assays and in vitro
      function assays (isolated vessels) were examined for the assessment of in vitro
      potency, selectivity of the ETA receptor against the ETB receptor, specificity
      for ET receptors, agonistic activities for ET receptors and the blocking manner
      of the compound on ET receptors. Chinese hamster ovary (CHO) cells expressing
      human ET receptors and tissue membrane preparations from both human and animals
      were used for the binding assays. The specificity of the compound against ET
      receptors was demonstrated using 116 and 9 receptor binding and enzyme assays,
      respectively. The agonistic activity and potency of the compound at tissue levels
      were examined using isolated vessels. We also demonstrated the effect of protein
      binding on the potency of the compound by adding a physiological concentration of
      serum albumin to the tissue baths. In vivo potency and features of the compound
      as a selective ETA-antagonist were confirmed using mice, rats and dogs
      exogenously treated with ET-1 or big ET-1. We also demonstrated the compound's
      duration of action and pharmacokinetics in animal models and intact animals,
      respectively. From these experiments, we found a nonpeptide, potent, orally
      active and long-lasting, highly selective ETA-receptor antagonist.

PMID- 12224444
TI  - Gateways to clinical trials.
AB  - Gateways to Clinical Trials is a guide to the most recent clinical trials in
      current literature and congresses. The data in the following tables has been
      retrieved from the Clinical Studies knowledge area of Prous Science Integrity,
      the drug discovery and development portal, http://integrity.prous.com. This issue
      focuses on the following selection of drugs: Aciclovir, alemtuzumab, alendronic
      acid sodium salt, alicaforsen sodium, alteplase, amifostine hydrate,
      antithymocyte globulin (equine), aspirin, atorvastatin calcium, azathioprine;
      Bacillus Calmette-Guerin, basiliximab, bicalutamide, bimatoprost, BMS-214662,
      brimonidine tartrate, buprenorphine hydrochloride; Cabergoline, carbamazepine,
      carboplatin, ciclosporine, cisplatin, cyclophosphamide; Daclizumab, desmopressin
      acetate, dihydroergotamine mesylate, dorzolamide hydrochloride, doxorubicin,
      dutasteride; Everolimus; Fluocinolone acetonide, frovatriptan, FTY-720,
      fulvestrant; Gabapentin, galantamine hydrobromide, ganciclovir, gemcitabine,
      glatiramer acetate; Hydrocodone bitartrate; Interferon beta, interferon beta-1a,
      interferon beta-1b, ipratropium bromide; Ketotifen; Lamivudine, latanoprost,
      levodopa, lidocaine hydrochloride, lonafarnib; Metformin hydrochloride,
      methylprednisolone, metoclopramide hydrochloride, mirtazapine, mitoxantrone
      hydrochloride, modafinil, muromonab-CD3, mycophenolate mofetil; NS-2330;
      Olopatadine hydrochloride, omalizumab, oxcarbazepine, oxycodone hydrochloride;
      Paclitaxel, paracetamol, piribedil, pramipexole hydrochloride, pravastatin
      sodium, prednisone; Quetiapine fumarate; Raloxifene hydrochloride, rituximab,
      rizatriptan sulfate, Ro-63-8695, ropinirole hydrochloride, rosiglitazone maleate;
      Simvastatin, siplizumab, sirolimus; Tacrolimus, tegaserod maleate, timolol
      maleate, tiotropium bromide, tipifarnib, tizanidine hydrochloride, tolterodine
      tartrate, topiramate, travoprost; Unoprostone isopropyl ester; Valganciclovir
      hydrochloride, visilizumab; Zidovudine.

PMID- 12224445
TI  - [New molecular biology detection methods for tick-borne infectious agents].
AB  - Tick-borne zoonotic pathogens are well known in many areas all over the world.
      Among the tick-borne transmitted diseases in Switzerland, Lyme disease caused by
      Borrelia burgdorferi, ehrlichiosis caused by various species of Ehrlichia and
      tick-borne encephalitis caused by the tick-borne encephalitis virus (TBEV) are
      the most important zoonotic diseases. Early diagnosis and treatment is necessary
      to prevent fatal infections and chronic damage to various tissues. Due to the
      variety of uncharacteristic clinical signs, tick-borne diseases are not easily
      recognized. Diagnosis is based on clinical findings, a record of tick exposure,
      and direct or indirect detection of the pathogen. Here we discuss briefly the
      most important tick-borne infections and their diagnosis with emphasis on a new
      molecular diagnostic tool--the real-time TaqMan PCR--and its importance for the
      diagnosis of tick-borne pathogens.

PMID- 12224446
TI  - [Horse breeding: genetic tests for the coat colors chestnut, bay and black.
      Results from a preliminary study in the Swiss Freiberger horse breed].
AB  - Coat color played an important role during domestication and formation of breeds.
      Livestock breeders often had special preferences for particular color phenotypes
      because they believed them to be associated with performance or fitness traits.
      Socio-cultural reasons might have had an influence on color selection as well.
      Recently genetic tests on DNA level got available to genotype in any individual
      horse for basic horse coat colors (chestnut, bay, black). In particular, hidden
      carriers of the recessive chestnut and black allele are recognizable with these
      tests. A sample of 162 Franches-Montagnes horses from Switzerland was genotyped
      for the alleles for chestnut and black. The analysis of allele frequencies
      revealed a high prevalence of the chestnut allele and a low frequency of the
      black allele in this population. Rare colors are in demand on the market. The
      statistical analysis of 1369 offspring from five stallions indicate, that darker
      shades of basic color phenotypes (dark chestnut, dark bay) follow a recessive
      mode of inheritance in the Franches-Montagnes horse breed.

PMID- 12224447
TI  - [Microsatellite analysis in a population of Baudet du Poitou donkeys].
AB  - A population of Baudet du Poitou donkeys was genetically characterized using
      microsatellites. The results were used to verify the pedigrees and to estimate
      the genetic variability. It could be confirmed that a equine parentage test kit
      works well for donkeys and that by using 13 microsatellites more than 99% of
      wrong pedigree informations would be detected. The genetic variability was
      comparable to a representative group of Baudet du Poitou donkeys in France.

PMID- 12224448
TI  - [Border disease in a flock of sheep].
AB  - This report describes border disease in a flock of sheep in Switzerland. In April
      2001, three ewes in a flock of 41 sheep gave birth to lambs that had generalized
      tremors and excessively hairy fleece. One of these, a three-week-old female lamb,
      was referred to our clinic for further diagnostic work-up. The lamb was very
      nervous, bleated constantly and had generalized muscle tremors, which were more
      pronounced in the head region. Hind end ataxia was observed, and the lamb was
      slow to correct its posture when the hind limbs were abducted, adducted or
      crossed. Blood samples were collected every six weeks to determine antibody
      titres to pestivirus and for virus isolation via cell culture. A skin biopsy
      sample was also collected and examined immunohistochemically for pestivirus
      antigen. Antibody titres in the first tests were suspicious and those of the
      second were negative. Pestivirus was identified in cell culture, and the skin
      biopsy sample was positive for pestivirus antigen. Blood samples were collected
      from all of the ewes and lambs and the buck for virus isolation via cell culture
      and determination of pestivirus antibody titres. Thirty-one animals were
      seropositive, six had borderline antibody titres and four were seronegative.
      Pestivirus was isolated from eight animals, which included the lamb described in
      this report. Of the virus-positive animals, three were seronegative, three others
      had borderline titres and two were seropositive. Six of the eight viruses
      isolated from cell culture were further characterized genetically via
      retrotranscription and polymerase chain reaction and subsequent sequencing. The
      phylogenetic analysis revealed that the causative agent was border disease virus.
      This is the first time that border disease virus has been isolated in
      Switzerland. The lamb referred to our clinic was observed for three months; it
      was then euthanatised and a postmortem examination was performed.
      Immunohistochemical examination of numerous organs revealed pestivirus antigen.
      The source of infection was though to be infected sheep from another flock, which
      shared a pasture. All antigen-positive animals were slaughtered.

PMID- 12224449
TI  - [Plant smoking materials].

PMID- 12224450
TI  - [Treatment of middle ear diseases].

PMID- 12224451
TI  - [Anemia in rheumatoid arthritis].

PMID- 12224452
TI  - [Kidney transplantation. Using living donors].

PMID- 12224453
TI  - [Can patent rights be an obstacle? Various views from clinical studies].

PMID- 12224454
TI  - [Ross procedure instead of heart transplantation. Recovery potential of the
      dysfunctional myocardium in heart failure caused by congenital aortic valve
      insufficiency].
AB  - The authors report a case of a child who presented in advanced valvular heart
      failure secondary to aortic regurgitation. Due to social circumstances heart
      transplantation was not a viable option, therefore a high risk pulmonary
      autograft aortic root replacement (Ross procedure) was performed. Following
      surgery a delayed but rather gratifying myocardial recovery was observed.
      CONCLUSION: This case represents the preserved recovery potential of the
      pediatric myocardium in end stage heart failure.

PMID- 12224455
TI  - [Percutaneous ethanol sclerotherapy of non-toxic nodular goiters--a clinical
      study of 76 patients].
AB  - INTRODUCTION: Ultrasonography-guided percutaneous ethanol injection (PEI) therapy
      is a new method for treating nodular goiters. PATIENTS AND METHODS: 76 patients
      with nontoxic nodular goiter (65 women, 11 men, mean age 49 years) underwent PEI
      in order to avoid surgery. In the first 14 patients with cystic nodule one
      session, while in the remaining 36 patients 3-8 sessions were performed. In each
      session after evacuation of the cysts half volume of absolute alcohol was
      injected into the nodule. In the cases of the 26 solid nodules each patient
      received a mean total dose of 0.98 ml (range 0.34-1.77 ml) ethanol per ml nodular
      volume. Ethanol was injected in a mean of 3.9 (range 2-8) sessions for solid
      nodules. Success was defined as shrinkage of the nodule to half or less compared
      to the pretreatment volume on 4.5 months and every later follow-up occasion.
      RESULTS: No serious side effects occurred. 2 previously operated patients became
      hypothyroid. In the case of cystic nodules treated on one session, in 4 of 14
      cases the therapy was unsuccessful. In patients treated on multiple occasions the
      success rate was significantly (p = 0.02, chi 2(1) = 5.06) higher; in 34 of 36
      cases. PEI was successful in 25 of 26 patients with solid nodules. A continuous
      shrinkage of the nodule was observed in those 25 patients who were followed for
      at least 2 years: the volume of the nodule was 35% at 1.5 month, 29% at 4.5
      month, 21% at 1 year and 17% of pretreatment volume at 2 years follow-up.
      CONCLUSIONS: PEI should be reserved for patients who cannot or will not undergo
      surgery. On the other hand, patients with recurrent nodular goiter requiring
      surgery form a subset where PEI can be proposed.

PMID- 12224456
TI  - [Dilemma in clinical practice: methods of tumor detection in patients with deep
      vein thrombosis].
AB  - Thrombosis being developed on the basis of acquired thrombophilia is a frequent
      and recognized complication of malignant diseases. Thrombosis may be presenting
      the first (and the only) symptom of cancers, therefore some kind of diagnostic
      procedure seems to be necessary for detecting malignancies. The occurrence of
      deep venous thrombosis with solid tumors had been studied, and the literature had
      been reviewed. The authors have discussed: 1. The epidemiology, 2. The prevalence
      and incidence of cancer with different types of thrombosis, 3. The most frequent
      malignancies, 4. The occult and undiagnosed tumors, 5. The cases at an early
      stage of cancer. Finally the authors tried to define a suitable diagnostic
      strategy. The point of this standard is that a detailed screening in patients at
      a high risk of cancer is reasonable even if there are no symptoms suggesting
      malignancy.

PMID- 12224457
TI  - [Visiting Hungarian medical homepages and portals].
AB  - INTRODUCTION: The Internet is a rapidly expanding network that handles
      miscellaneous data. Everyone or every organisation can join to it. The Internet
      covers more than 800 millions of documents and it is a hard task to find the
      relevant and up-to-date information among them. Search engines, portals and
      virtual catalogues back the retrieval of data. AIM: The aim of this study is to
      give insight into the presence of Hungarian health institutions on the Internet,
      and we try to find information about the quality of these Internet resources.
      SCOPE AND RESULT: Based upon the analysis of 72 Web Pages we drew the conclusion
      that the Hungarian medical homepages are not prepared well enough to supply
      content services. There are, however, some examples to very good solutions. The
      number of medical portals containing exact, up-to-date information is growing
      continuously.

PMID- 12224458
TI  - [Military surgeons in the Hungarian War of Independence, 1848-49].

PMID- 12224459
TI  - [Effects of BSE on consumer attitudes and behavior].
AB  - The extremely high media emphasis of the BSE issue during the period December
      2000 to February 2001 has caused considerable short term public concern. A
      significant amount of this concern was due to an intensive communication of
      pictures. Pictures are "fast shots into the brain" (Kroeber-Riel). Pictured
      stimuli run under the cognitive control of the recipients effecting the consumer
      below the threshold of consciousness. However, the issue has fallen into oblivion
      very soon. In summer 2001 the public concern was not higher than before the BSE
      crisis. The perception of product quality regained a "normal level". The public
      concern has caused a considerable decline of the demand for beef and an increase
      of demand for substitutes and organic meat. When the media emphasis of the BSE
      issue diminished, the beef demand recovered but did not reach the pre-crisis
      level again. However, the BSE crisis has intensified animal welfare concerns,
      polarized public opinion about food and agriculture and had big effects in the
      political sphere. Furthermore, the BSE crisis has led to additional--politically
      supported--activities of the organic food suppliers causing a further growth of
      this market segment.

PMID- 12224460
TI  - [Basic research on BSE transmission to people].
AB  - Prion diseases of animal and man belong to neurological diseases with amyloidal
      deposition of the respective proteins. As to prion disease, the cellular
      prionprotein is in its abnormal isoform(s) an essential component of prionprotein
      aggregates found in affected tissue. In contrast to all neurodegenerative
      diseases like Morbus Alzheimer or Huntington's disease, prion diseases are
      transmissible. Therefore, prion diseases were designated Transmissible Spongiform
      Encephalopathies (TSE). The diseases are well known since decades. Scrapie was
      first described around 1750, a BSE case was reported in the 1850, most likely a
      misdiagnosis, and in 1920/1930 the human Creutzfeldt-Jakob disease (CJD) had been
      described. Transmission of CJD i.e. Kuru had been suspected in the early 1950s
      and erronously classified as slow virus disease. The CJD transmission posed a
      problem to humans when transplants from CJD cases were used for treatment.
      Fortunately, these iatrogenic transmissions remained limited. But with the advent
      of BSE and appearance of variant CJD cases in the UK and some places in Europe
      scientists suspected that transmission from cattle to man could have happened.
      From animal models we know of successful transmission via several routes. Species
      barriers do not completely prevent transmission. Rather transmission barriers
      might exist controlling individual susceptibility against prions. Modes of
      transmission, susceptibility for transmission, identification of receptor
      molecules as well as molecular mechanisms of the transmission process are
      intensely investigated. Current knowledge let us to assume that inapparent stages
      of prion infection pretend a (not existing) species barrier. This inapparent
      infection preceeds overt disease and, thus, most re-search focuses on the
      development of highly sensitive assay systems for detection of minute amounts of
      pathological prionprotein in suspected cases. Inapparence also should warn us to
      underestimate BSE or human vCJD cases; at present, 124 in Europe and one probable
      case in Hongkong (7 March 2002). Whether BSE had spread to other parts of the
      world by animal nutrition components or meat can neither be excluded nor
      confirmed at this time. New data on transmission and consequences of BSE for the
      human population are summarized in this review.

PMID- 12224461
TI  - [Consequences of BSE/TSE for the clinical diagnostic in cattle and sheep].
AB  - The first case of Bovine Spongiform Encephalopathy (BSE) in Germany induced a
      profound irritation not only of the consumers but also of the farmers and the
      veterinarians in Germany. The following BSE-crisis accelerated the structural
      changes in Beef and Dairy industries. The analysis of the detected BSE-cases of
      the last years in Germany and Switzerland shows that the sensitivity of BSE-tests
      is much higher in clinically preselected BSE-suspected cases compared to BSE
      tests in normal slaughter cattle. Therefore it is necessary for an effective
      battle against BSE that clinical cases of CNS-diseases and disturbances of the
      locomotion especially in cows around partus should be clarified etiologically. If
      intra vitam the etiology of the disease can not be diagnosed by clinical and
      laboratory investigation of blood, urine and liquor samples and the therapy
      induces no improvement, the case has to be notified at the local veterinary
      officer. In the same way cases of Scrapie in sheep have to be handled. In sheep
      genotyping gives the opportunity to select for Scrapie resistance. In contrary to
      cattle with BSE Scrapie can be diagnosed intra vitam already before clinical
      symptoms occur by immunohistochemical investigations for Scrapie prion protein of
      tonsillar biopsies. These two diagnostic tools open new ways for fighting against
      Transmissible Spongiform Encephalopathies in sheep.

PMID- 12224462
TI  - [Meat and potential risks].
AB  - By the term "meat" the consumer understands muscle meat, that is skeletal muscle.
      The german regulations, the "Leitsatze fur Fleisch und Fleischerzeugnisse" as
      well as the Codex Alimentarius define meat in a much broader sense to include all
      edible parts of slaughtered or shot warm-blooded animals (skeletal muscles, fat,
      heart, gut, liver etc). Therefore, a differentiated procedure is required when
      the risk of BSE transmission by meat has to be estimated. This must be based on
      knowledge of occurrence, amount, and persistence of BSE agents in the organs of
      animals. The risk evaluation has to include further factors: differences between
      animal species, age of the animal at the time of slaughter, the possibility of
      contamination during the slaughtering and cutting process, and--as far as meat
      products are concerned--the processing technology. To date there are no
      indications for the existence of transmissible spongiform encephalopathy in pigs,
      poultry and fish, even though BSE has been transmitted to pigs experimentally by
      intracranial administration. Muscle meat of these species can be considered safe.
      Muscle meat of experimentally infected cattle in the preclinical stage and even
      of animals with clinically manifest BSE has not shown infectivity in homologous
      and autologous bioassays performed so far. This finding justifies the assumption
      that the risk of BSE exposure by the consumption of beef can be classified as
      extremely low. Nevertheless, the absence of a proof of infectivity can at present
      not be equated with absence of BSE agents. This is because of the limits of
      sensitivity of the bioassays and because muscle meat does contain non-muscle
      tissue such as connective tissue collagen, nerve and lymph tissue and blood
      vessels.

PMID- 12224463
TI  - [BSE: milk and risk potential?].
AB  - A potential BSE risk for milk and milk products has to be evaluated by means of
      risk analysis, especially risk assessment. The 3rd element of risk assessment-
      hazard exposition--is of decisive significance. In 1997, the Scientific Steering
      Committee of the European Commission has categorized risk materials in 4 classes.
      Colostrum, milk and tissues of the mammary gland have been classified in category
      4, i.e. "infectivity not detected". A secondary contamination of the milk can be
      excluded (living animals). However, the term "not detected" refers also to the
      low sensitivity of the mouse test, which has to be taken into consideration.
      Therefore, in 2000 investigations started in Great Britain to test milk
      fractions, especially the fraction of somatic cells, for the possible occurrence
      of prions, using newly developed and highly sensitive methods. Results can not be
      expected before 2003 at the earliest. In case prions would be detected, their
      biological activity has to be demonstrated in order to develop an appropriate
      risk assessment for the consumer. Investigations in Great Britain in the early
      nineties of the last century with suckling cows under practical conditions have
      shown no indications of a BSE transfer via the milk to the calves. Therefore, the
      statement of national and international organizations is still valid, that milk
      can be regarded safe according to the present state of scientific knowledge.

PMID- 12224464
TI  - [Disposal of animal byproducts, dead and slaughtered animals].
AB  - The current state of epidemiological knowledge about BSE clearly indicates that
      certain practices in carcass rendering had a significant impact on maintenance
      and spreading of BSE in the cattle population. This awareness did not come up
      spontaneously. As a reflection community legislation continuously developed and
      still does. The decisive move was done in the year 2000 by eliminating ruminant
      tissues with a high infectious potential with regard to BSE (specified risk
      material--SRM) from the human and animal feed chains. This step as well as the
      subsequent feed ban for all farm animals dramatically changed the logistical as
      well as the economical preconditions of the rendering industry. In fact the basic
      treatment (pressure cooking) remained almost unchanged. But instead of physically
      recycling the products they are nowadays predominantly used as an energy source
      in industry. In case of products that originate from the treatment of SRM burning
      is mandatory. These changes require a well adapted and intensified official
      supervision.

PMID- 12224465
TI  - [Economic consequences of BSE in Germany].
AB  - It is the objective of this article to elaborate selected economic consequences
      of BSE in Germany on economic as well as political markets. Strong effects
      arising from BSE on meat markets do exist, which have a short-run and a medium
      run component. Quantitative analyses of beef demand have shown for years that
      stark short-run effects of new BSE information occur and a significant medium-run
      change of preferences against red meats. The impacts of BSE on the political
      market were important, too. The German BSE crisis was utilized for a substantial
      change in the government's perception of agricultural and food policy, often
      called "Agrarwende". The concept includes altered instruments of agricultural
      protection, which imply new economic problems. The role of markets in providing
      incentives to produce food quality is generally underestimated within the new
      policy.

PMID- 12224466
TI  - [Animal feeding and feed legislation after the detection of the first indigenous
      BSE cases in Germany].
AB  - In Great Britain, even the earliest tangible signs indicating the epidemiologic
      significance of meat and bone meal in the spreading of BSE soon gave rise to
      increasingly rigorous legislative measures regulating animal feedstuffs. In 1994
      a ban on the feeding of animal proteins to ruminants was implemented throughout
      the entire EU. But until the first BSE cases were actually confirmed in locally
      raised cattle (November 2000), feeding practice and legislation more or less in
      Germany remained unaffected by the efforts undertaken in Great Britain. This
      situation was suddenly changed on 1 December, 2000, when the so-called
      "Verfutterungsverbot" was put into effect, a law which drastically extended bans
      regarding the feedstuffs (including fishmeal and animal fats) as well as the
      species concerned (all animals used in food production). In 2001 the
      "contamination" phenomenon (ingredients of animal origin were detected in mixed
      feeds) became a vital issue for the feed industry; through the media, the subject
      "feedstuff safety" gained a previously unseen level of public awareness. Those
      circles concerned with mixed feed production and animal husbandry were
      increasingly confronted with the consequences of the "Verfutterungsverbot"
      (availability and pricing of substitute ingredients; the demand for amino acids
      and inorganic sources of phosphorus; problems finding adequate substitutes for
      animal fats; poor digestibility of alternative components such as indigenous
      legumes or vegetable fats in calf diets; lower utilization rate of original
      phosphorus in mixed feeds with negative consequences for skeletal development).
      With the conditional approval of fishmeal (except in feeds for ruminants) the
      situation has eased again to a certain degree; on the EU level there are
      increasing signals pointing toward a political intention to reinstate the
      utilization of by-products of slaughtered animals qualified for human consumption
      (with the exception of fallen/dead animals and specific risk material) in poultry
      and swine feeding. In Germany, at least, the question of animal fat utilization
      for food-producing animals is still unsolved.

PMID- 12224467
TI  - [BSE--consequences for slaughtering, cutting and employer's protection].
AB  - The conventional slaughtering of cattle includes some critical process stages
      where a carry over of BSE-risk material (brain, spinal cord) on the meat can
      occur. These processes are captive bolt stunning, cut off the head and first of
      all sawing the spine lengthways. Alternative stunning methods like electrical
      stunning or concussion stunning are under investigation, nevertheless they are in
      the moment no useful alternatives for most of the slaughter houses. The most
      promising methods available at present for minimising the risk appear to be in
      manual cattle slaughtering boning the entire carcass, either still warm or
      refrigerated and in industrial beef cattle slaughtering extraction of the spinal
      cord by vacuum from the whole carcass followed by conventional sawing or
      completely sawing out the spine including spinal ganglia. Working processes,
      including the cutting or exposure of risk material, are a risk for the employer's
      too. Special protective measures must be taken.

PMID- 12224468
TI  - [BSE--present and future legal requirements].
AB  - After BSE had first been recorded in November 2000 in a bovine animal born in
      Germany, national measures had immediately been taken and a great number of
      decisions taken at Community level resulting in substantial risk minimization. On
      1 July 2001, Regulation No. 999/2001/EC came into force compiling all protection
      measures against BSE under Community law, including supplementary transitional
      measures. On the basis of the current legal situation, the evolving further
      development of key protection measures is described in the following.

PMID- 12224469
TI  - Frequency evolution during tonic-clonic seizures.
AB  - By using the Short Time Fourier Transform, we analyzed the EEG frequency
      evolution during tonic-clonic seizures on 18 scalp recordings corresponding to 7
      patients admitted for Video-EEG monitoring. This information was correlated with
      clinical findings observed in the video recordings. From the time-frequency
      plots, we recognized patterns related with brain activity even when embedded in a
      background of muscle artifacts. In 13/18 seizures we found a clear frequency
      dynamics characterized by an activity originally localized at about 8 Hz, later
      slowing down to about 1.5 Hz. In the remaining cases muscle artifacts hinder the
      disclosure of a clear frequency evolution. The clonic phases started when the
      main frequency slowed down to about 3 Hz. We conclude that the Short Time Fourier
      Transform is very useful for a quantitative analysis of epileptic seizures,
      especially when muscle artifacts contaminate the recordings. We further conclude
      that the clonic phase starts as a response to brain activity that can be only
      established when brain oscillations are slow enough to be followed by the
      muscles.

PMID- 12224470
TI  - Repetitive nerve stimulation and muscle membrane excitability: case report and
      review.
AB  - Few muscle disorders can be diagnosed by repetitive nerve stimulation (RNS).
      Decreasing compound muscle action potentials (CMAP) on high frequency RNS is
      recorded in muscle channelopathies, and particularly in sporadic and recessive
      congenital myotonia. In this myopathy, decreasing CMAP after exercise test and
      RNS are the most sensitive electrophysiological in detecting muscle membrane
      dysfunction and are considered highly informative even in mildly symptomatic
      patients. We report on a patient with excercise-induced diffuse muscle cramps and
      myalgia; muscle biopsy and laboratory investigations were normal. Decreasing CMAP
      on high frequency RNS suggested muscle membrane conduction anomalies and, though
      clinical and electrical myotonia was not detected, the neurophysiological finding
      raised the suspicion of congenital myotonia and addressed to molecular
      investigation.

PMID- 12224471
TI  - Mechanomyographic and electromyographic amplitude and frequency responses from
      the superficial quadriceps femoris muscles during maximal, eccentric isokinetic
      muscle actions.
AB  - The purposes of this study were to examine the effects of gender and muscle
      (vastus lateralis = VL, rectus femoris = RF, and vastus medialis = VM) on the
      velocity-related patterns for peak torque (PT), mean power output (MP),
      mechanomyographic (MMG) amplitude, electromyographic (EMG) amplitude, MMG mean
      power frequency (MPF), and EMG MPF during maximal, eccentric isokinetic muscle
      actions. Thirteen females (mean +/- SD age = 21 +/- 1 years) and eleven males
      (mean +/- SD age = 21 +/- 2 years) volunteered for this investigation. PT and MP
      were measured on a calibrated Cybex 6000 dynamometer at randomly ordered
      velocities of 60, 120, and 180 degrees.s-1, while MMG and EMG signals were
      recorded simultaneously from the VL, RF, and VM muscles. The results indicated no
      gender-related differences for the patterns of PT, MP, MMG amplitude, EMG
      amplitude, MMG MPF, or EMG MPF. Furthermore, no muscle-related differences were
      found for the patterns of MMG amplitude, EMG amplitude, or MMG MPF. The
      normalized values for MP and MMG amplitude increased from 60 to 180 degrees.s-1
      (60 degrees.s-1 < 120 degrees.s-1 < 180 degrees.s-1). PT and EMG MPF remained
      unchanged across velocity, while EMG amplitude remained unchanged from 60 to 120
      degrees.s-1, but decreased (approximately 10%) from 120 to 180 degrees.s-1. The
      findings indicated a close association between the patterns for MP and MMG
      amplitude, and a similarity between the patterns for PT, EMG amplitude, and EMG
      MPF across velocity. Therefore, the present findings suggested that motor unit
      recruitment (EMG amplitude), firing rate (MMG MPF), and muscle fiber action
      potential conduction velocity (EMG MPF) exhibited velocity-related patterns that
      were similar to PT production, while MMG amplitude was more closely associated
      with MP.

PMID- 12224472
TI  - Torque-EMG relationships in normal and spastic muscles.
AB  - The linearity of the relationship between torque and electromyographic (EMG)
      activation has been widely debated for years, yet remains unresolved. Despite
      limitations and possible inaccuracies, an assumption of linearity is often made
      to simplify the relationship between these variables for computational and
      descriptive purposes. Although typically derived from isometric test conditions,
      these relationships have also been extrapolated, perhaps invalidly, to conditions
      where joint velocity and length are changing. The purpose of this study was to
      examine the degree of linearity between hamstring and quadriceps torques and
      their respective EMG signals, and to compare the slopes of these relationships in
      normal and spastic muscles at varying muscle lengths and conditions. We
      hypothesized that relationships would be linear for all muscles tested in both
      subject groups; however, slopes would differ across the two muscles, the three
      muscle lengths tested, and the two subject groups. We further hypothesized that
      the degree of linearity during an isotonic task would be less than for the
      isometric one, particularly for patients with spasticity who may demonstrate
      abnormal responses to changes in muscle length. Results indicated that torque-
      EMG relationships were linear for all subjects during isometric contractions,
      regardless of group, muscle, or knee angle. However, the degree of linearity was
      significantly less in CP in both conditions; and within the CP group, was less
      during isotonic compared to isometric conditions. Slope values differed between
      muscles at some lengths, across muscle lengths in the quadriceps, and subjects
      with CP showed consistently lower slopes for all quadriceps values. These data in
      general support the robustness of the linear assumption in isometric conditions
      for the knee musculature, caution against extrapolation to isotonic conditions
      particularly for those with movement abnormalities, and suggest that slope
      differences may provide valuable insights into pathology and warrant further
      investigation.

PMID- 12224473
TI  - Neural mechanisms underlying the effect of transcutaneous electrical nerve
      stimulation in humans.
AB  - The aim of the present study was to observe the effect of transcutaneous
      electrical nerve stimulation (TENS) and to determine which group of afferent
      nerve fibers plays a role in this effect. The subjects were 43 healthy humans.
      The subjects received placebo intervention, TENS to the common peroneal nerve or
      to the cutaneous branches of the peroneal nerve. All TENS interventions decreased
      the Hmax/Mmax ratio. All the TENS interventions but the TENS below the motor
      threshold to the common peroneal nerve increased the H-reflex latency. The effect
      of TENS on Ia-mediated presynaptic inhibition varied according to the
      stimulation. Both group Ia and group II cutaneous afferent nerve fibers from the
      peroneal nerve are considered to mediate the inhibitory effect on the soleus
      motoneuron pool. Group II cutaneous afferent nerve fibers are considered to play
      an important role in increasing soleus H-reflex latency.

PMID- 12224474
TI  - Recovery from spinal cord injury achieved by 3 months of coordination dynamic
      therapy.
AB  - Coordination dynamic therapy was applied to 18 patients (average age 31 years)
      after a spinal cord injury between C4/5 and L4/5; the therapy was administered on
      average 5 years after the injury for a minimum of 3 months. All complete spinal
      cord lesions became incomplete, i.e. motor functions improved below the lesion
      level, including trunk stability and arm, hand and leg functions. The
      organization of the CNS, quantified by the coordination dynamics between arm and
      leg movements, improved by 42% for forward and by 49% for backward moving when
      exercising on a special coordination dynamic therapy device. The improvements of
      the coordination dynamics were 53%, 32% and 48% for lesions in the cervical,
      thoracic, and lumbar range, respectively. The plasticity for spinal cord lesions
      was thus higher when the intumescence was lesioned. Since the coordination
      dynamics did not change substantially prior to coordination dynamic therapy, did
      further improve with continued therapy, and worsened when the therapy was
      terminated, it is concluded that the improvement of CNS functioning above and
      below the spinal cord lesion level was due to the therapy. Since in stroke and
      traumatic brain lesion the CNS functioning further improved if the therapy was
      continued over longer time periods beyond 3 months, it is suggested that spinal
      cord lesions can partly be cured if coordination dynamic therapy is administered
      for 1 to 2 years.

PMID- 12224475
TI  - Role of the rectosigmoid pacemaker and electric activity in rectal motility:
      mechanism and clinical significance.
AB  - BACKGROUND: The rectum exhibits electric activity in the form of slow waves or
      pacesetter potentials (PPs) and action potentials (APs), which are suggested to
      be initiated from a rectosigmoid pacemaker (RSP). We hypothesized that the RSP
      and electric waves are responsible for rectal motility. This hypothesis was
      investigated. METHODS: The rectum of 13 mongrel dogs was exposed through an
      abdominal incision, and 3 electrodes were fixed serially to the rectal serosa.
      The rectal pressure was measured by a 6 F saline-perfused catheter and the rectal
      electromechanical response to rectal balloon distension in increments of 5 ml of
      air was registered. The test was repeated after rectosigmoid junction (RSJ)
      anesthetization by 20 minutes and 3 hours using xylocaine injection. It was done
      also after saline instead of xylocaine injection. RESULTS: PPs and APs were
      recorded and had the same frequency, amplitude and conduction velocity from the 3
      electrodes of the same animal. APs occurred randomly and were coupled with
      elevated rectal pressure. Rectal balloon distension produced increase of the
      rectal electric activity and pressure, which increased with the increase of the
      rectal distension until, at a mean volume of 31.2 +/- 5.4 ml, the balloon was
      expelled to the exterior. RSJ anesthetization abolished the rectal electric waves
      and effected no balloon expulsion with high volume rectal distension. The rectal
      waves appeared after waning of the anesthetic effect. Saline injection into the
      RSJ produced no significant effect on the rectal electromechanical activity.
      CONCLUSION: Rectal electric waves are suggested to be initiated from the RSP and
      to be responsible for the rectal motor activity. Incremental rectal balloon
      distension effected progressive increase of the rectal electromechanical activity
      until the balloon was expelled to the exterior RSJ anesthetization blocked the
      electric waves and the electromechanical response to rectal distension. These
      results have probably clinical significance when performing electrorectograms for
      various rectal pathologic conditions as well as when applying an artificial
      pacemaker to the non-contractile rectum.

PMID- 12224476
TI  - [The post-whiplash syndrome: don't treat, but unravel].
AB  - There are two phases in the postwhiplash syndrome. The first phase (following a
      sufficiently serious accident) is characterised by pain in the neck caused by
      soft tissue contusion. In this phase, an explanation and the advice to start
      moving the neck again gradually after a brief period of rest are sufficient. If
      this phase is followed by a transition to complaints that can no longer be
      explained by the physical consequences of the accident, we speak of a chronic
      postwhiplash syndrome. In such a case there are factors besides the trauma that
      either induce the complaints or cause them to persist. Unless these factors are
      eliminated (the biopsychosocial model), the chance of success of any form of
      treatment is slight. There are indications that therapies directed at aspects of
      behavioural psychology can make an important contribution to recovery.

PMID- 12224477
TI  - [Population screening for uterine cervix cancer: the negative effects of
      insufficient knowledge as to what is normal and abnormal].
AB  - Screening for asymptomatic disease seems attractive but has severe disadvantages
      if not evaluated properly. The side-effects may be greater than the benefits,
      especially in countries with a very low incidence of the disease. In 1997,
      invasive cervical cancer was diagnosed in approximately 700 women in the
      Netherlands. Knowledge about the effect of cervical cancer screening has been
      derived from observational studies since randomised trials are non-existent. For
      many findings in the cervical smear we do not know the natural course. As a
      result, a substantial number of women (10%) are advised to undergo repeated
      screening after a shorter interval than the regular screening interval of 3 years
      (since 1996 this is 5 years). In 1996, a new guideline was developed to limit the
      number of women in the repeat circuit. The percentage of women with a Pap 2 smear
      (mild dysplasia) decreased from 10% in 1992 to 2% in 1998. However, the follow-up
      with repeat smears was less rigorous: for 28% no repeat smear was performed after
      2 years and 3 months, compared to 10% in 1992. Incomplete follow-up will lead to
      a decreased cost-effectiveness of the programme, which already appears to be only
      marginally effective. The value of screening for cervical cancer should be
      reconsidered from time to time.

PMID- 12224478
TI  - [Possibilities and limitations of genetic research; an advisory report from the
      Advisory Council on Health Research].
AB  - The Raad voor Gezondheidsonderzoek [Advisory Council on Health Research] has
      issued a report entitled 'New applications of genetic information in health care:
      which knowledge is needed?' The report is limited to areas where research is
      likely to have consequences within the relatively short time-span of a few years.
      These include genetics in diagnostics and screening, pharmacogenetics, and
      certain inherited diseases in adult age. Complex diseases such as multifactorial
      ones are not addressed. The report provides a useful overview of the prospects
      and problems in genetic research and how it will be applied in the years to come.
      Societal consequences of genetic research are also discussed. To enhance the
      understanding of complex diseases, epidemiological studies with long-term follow
      up that combine genetic data with other data are essential. At the same time,
      potential privacy risks should be acknowledged and scientists should take extreme
      care in collecting, handling and analysing such data. The Netherlands Federation
      of Societies for Medical Research has produced guidelines which researchers
      should follow when carrying out their research.

PMID- 12224479
TI  - [Dermatoscopy: an asset in the clinical assessment of pigmented skin lesions].
AB  - Dermatoscopy is a non-invasive technique for the clinical diagnosis of pigmented
      skin lesions: a simple contact skin-surface microscope with a 10-fold
      magnification is used; the application of oil makes the horny layer translucent,
      as a result of which several additional criteria become available for the
      diagnosis of pigmented lesions. The evaluation is based on an algorithm involving
      asymmetry, border, colour and differential structure; another type of evaluation
      involves pattern analysis (global assessment, detailed assessment, assessment of
      the pigment network). The evaluation of these criteria requires formal training,
      after which the diagnostic skills of dermatologists have been found to increase;
      in non-dermatologists these skills decreased. Dermatoscopy has become an
      indispensible aid in clinical dermatology.

PMID- 12224480
TI  - [A repeat advice no longer applies for cervical smears without endocervical cells
      in population studies for cervical cancer].
AB  - Recent Dutch and non-Dutch studies have shown that the absence of endocervical
      cells (ecc-) in an adequate cervical smear does not present an increased risk for
      the presence or occurrence of cervical cancer or premalignant abnormalities in a
      later phase. Based on these findings, the Coordination Committee Cervical Cancer
      Screening of the Dutch Health Insurance Council had advised dropping the repeat
      advice for non-abnormal ecc- smears by January 1st 2002. The National Health
      Insurance Council has agreed to this advice. The following measures have been
      taken: (a) no repeat advice for ecc- smears; in the case of negative findings the
      woman waits until the next five-yearly invitation from the screening programme;
      (b) whether the portio cervicis was seen has to be stated on the national request
      form; (c) the reporting of an ecc- in the cytology report and periodical feedback
      to general practitioners remains unchanged; (d) in the case of a non-abnormal ecc
      smear with an uninspected portio or doubts as to whether the transformation zone
      was adequately scraped, either the smear will have to be repeated or the patient
      will have to be referred to the gynaecologist.

PMID- 12224481
TI  - [From gene to disease: from the ABCA4 gene to Stargardt disease, cone-rod
      dystrophy and retinitis pigmentosa].
AB  - Autosomal recessive Stargardt disease is caused by mutations in the ABCA4 gene.
      Mutations in ABCA4 are also found in two-thirds of cases with autosomal recessive
      cone-rod dystrophy, and a small fraction of patients with autosomal recessive
      retinitis pigmentosa. Patients with autosomal recessive retinitis pigmentosa, the
      most severe of these three phenotypes, invariably carry ABCA4 inactivating
      mutations; patients with autosomal recessive cone-rod dystrophy and Stargardt
      disease carry combinations of mutations that do not completely inactivate the
      retina specific 'ATP-binding cassette transporter' (ABCR) protein. DNA
      diagnostics is complicated by the high allelic heterogeneity and the uncertainty
      as to whether some ABCA4 variants are pathological. Nevertheless, ABCA4 mutation
      analysis is particularly important for patients with cone-rod dystrophy to
      confirm the autosomal recessive mode of inheritance.

PMID- 12224482
TI  - [Diagnostic image (102). A man with an itching foot. Larva migrans cutanea].
AB  - A 27-year-old man presented with larva migrans cutanea on his left foot after a
      journey to the Philippines.

PMID- 12224483
TI  - [Less pap-2 results ('minor abnormalities') in the population screening for
      cervical cancer since the introduction of new guidelines in 1996].
AB  - OBJECTIVE: To determine whether the 1996 implementation of new guidelines for the
      classification and management of cervical smears in the Dutch population
      screening programme for cervical cancer (i.e. inflammatory symptoms are no longer
      classified as moderate dysplasia and women with two smears with moderate
      dysplasia are referred directly to the gynaecologist) was followed by a reduction
      in both the number of women with repeat smears and the length of follow-up.
      METHODS: The results of all smears of women aged 35-54 years from 1990 onwards,
      were retrieved from the Dutch Network and National Database for Pathology
      (PALGA). The percentage of smears with moderate dysplasia was analysed with
      respect to time. The percentage of women with a histological examination during
      the follow-up phase of the population screening programme (1990 and 1991) was
      compared with that for the new screening programme (1996). RESULTS: Following the
      implementation of the new guidelines, the percentage of smears with moderate
      dysplasia was reduced from 10% to 2%. The percentage of women with a histological
      examination during the follow up of two smears with moderate dysplasia remained
      the same. The new recommendations for additional smears were not followed: for
      28% no repeat smear was available after 2.25 years versus 10% in 1992. There were
      indications that the referral of women with two cases of moderate dysplasia to a
      gynaecologist was not strictly adhered to either. Since the introduction of the
      new guidelines, the estimated percentage of women that should be referred to the
      gynaecologist following smears with moderate dysplasia has not changed.
      CONCLUSION: The new recommendations have lead to fewer smears being classified as
      moderate dysplasia. The long-term effects, such as a reduction in the length of
      the follow-up period, can only be analysed in a few years time.

PMID- 12224484
TI  - [Nephrotic syndrome as a paraneoplastic symptom of Hodgkin's disease in two
      children].
AB  - A 13-year-old girl and a 3-year-old boy presented with the clinical symptoms of
      nephrotic syndrome. Both patients developed a nodular mass in the cervical
      region, which appeared to be due to Hodgkin's disease. The renal disease was a
      paraneoplastic phenomenon of Hodgkin's disease. Chemotherapy given for Hodgkin's
      disease also cured the nephrotic syndrome. A few years later one of the patients
      experienced a recurrent episode of nephrotic syndrome in conjunction with a
      recurrence of Hodgkin's disease but this was once again treated successfully.
      Nephrotic syndrome is a known but rare paraneoplastic syndrome accompanying
      Hodgkin's disease. It is thought that T cell dysfunction leads to a secretion of
      cytokines which alters the permeability of the glomerular basement membrane. This
      dysfunction is not only apparent during the period of active disease and this
      could clarify why paraneoplastic syndrome can exist or recur outside the period
      in which the malignancy is overt. The clear recognition of a paraneoplastic
      syndrome is important, as it is often only necessary to treat the malignancy.

PMID- 12224485
TI  - [Recurrent attacks of angioedema ascribed to the use of estrogen preparations and
      a pregnancy (hereditary angioedema type 3)].
AB  - A woman experienced recurrent attacks of angioedema from the age of 17 to 21
      years and these appeared to be associated with the use of oestrogens. After
      stopping the medication her complaints disappeared, but they returned during her
      first pregnancy. Angioedema is a serious condition, which can lead to acute
      abdominal symptoms, oedema of the upper respiratory tract and death by
      asphyxiation. The most well-known cause is hereditary angioedema, an autosomal
      dominant disorder that is characterized by deficiency of C1 esterase inhibitor
      (C1-INH). Recently, a new type of hereditary angioedema (type 3) has been
      reported that occurs exclusively in women and is characterised by oestrogen
      dependency (both endogenous and exogenous), normal C1-INH concentrations and
      severe attacks of angioedema, which are clinically indistinguishable from the
      classic form.

PMID- 12224486
TI  - [Chemoradiotherapy in locally advanced cancers of the uterine neck. Retrospective
      study of 92 patients treated at the Institute Curie between 1986 and 1998]].
AB  - PURPOSE: The prognosis of locally advanced cervix cancers is poor with metastatic
      and local recurrence risks. Recent publications reported that concurrent
      chemotherapy and pelvic radiation increased local control compared to
      radiotherapy alone. Chemotherapy could also decrease metastatic recurrences. We
      report 92 cases of patients with locally advanced cervix cancer treated between
      1986 and 1998 at the Institut Curie. PATIENTS AND METHODS: Concurrent
      chemoradiation was exclusive in 51 cases and added to surgery in 41 cases.
      Chemotherapy with 5FU-Cisplatin-Mitomycin C-Vindesin (protocol A) was performed
      for 43% of patients and 57% of them received 5FU-Cisplatin alone (protocol B).
      RESULTS: Median follow-up was 64 months (6-149 months). Five-year disease-free
      survival rate was 47% and local control rate was 70%. Disease-free survival was
      correlated with therapeutic response. After exclusive chemoradiation, the good
      responsive patients had a better DFS (54% vs 26%, p = 0.018). In the surgery
      group, those patients with sterilized lymph nodes and tumours had also a higher
      DFS (76% vs 47%, p = 0.036). Toxicity was higher with protocol A. CONCLUSION:
      From our study, it appears that local control of advanced cervix cancers is
      better with combined chemoradiotherapy but disease-free survival stays low
      according to the metastatic evolution. Metastasis without local recurrence
      remained frequent in our study. 5FU-CDDP chemotherapy has a lower toxicity and is
      as effective as 5FU-CDDP-Mitomycin C-Vindesin protocol, in association with
      radiotherapy.

PMID- 12224487
TI  - [Biological variables and stratification of patients with inoperable non-small
      cell bronchial cancer: recommendations for future trials].
AB  - OBJECTIVE: To identify, through a review of the literature, the laboratory
      variables that would allow a more accurate stratification of unresected non small
      cell lung cancer patients who participate in clinical trials. METHOD: Systematic
      review, without meta-analysis, following the recommendations of the International
      Federation of Clinical Chemistry and Laboratory Medicine, and taking into account
      the Consolidated Standards of Reporting Trials statement. RESULTS: Of 1106
      publications retrieved, we were able to include only fourteen studies in our
      review. Available evidence would support the use of several laboratory variables
      as prognostic covariables to stratify non resected non small-cell lung cancer
      patients in clinical trials, but blood haemoglobin would be the only one that
      could be recommended on a routine basis, and only in patients treated with
      radiotherapy (three studies out of three). The possible consequences in terms of
      therapeutic decision of haemoglobin measurements remain however to be clarified.
      CONCLUSION: Until better designed studies are published, a number of arguments
      would support the pre-treatment measurements of the following variables in
      patients participating in clinical trials: blood haemoglobin, white blood cell
      count with differential, serum LDH, albumin, calcium, and NSE. Further studies
      would also be necessary to support the addition to this list, of other tumour
      markers (including Cyfra 21-1), and/or measurements during or after treatment.

PMID- 12224488
TI  - [Operable stage IB and II cancer of the uterine neck: retrospective comparison
      between preoperative utero-vaginal curietherapy and initial surgery followed by
      radiotherapy].
AB  - PURPOSE: To identify prognostic factors and treatment toxicity in a series of
      operable stages IB and II cervical carcinomas. PATIENTS AND METHODS: Between May
      1972 and January 1994, 414 patients (pts) with cervical carcinoma staged
      according to the 1995 FIGO staging system underwent radical hysterectomy with (n
      = 380) or without (n = 34) bilateral pelvic lymph node dissection. Lateral
      ovarian transposition to preserve ovarian function was performed on 12 pts. The
      methods of radiation therapy (RT) were not randomised and depended on the usual
      practices of the surgical teams. Group I: 168 pts received postoperative RT (64
      pts received vaginal brachytherapy alone [mean total dose (MD): 50 Gy], 93 pts
      had external beam pelvis RT (EBPRT) [MD: 45 Gy over 5 weeks] followed by vaginal
      brachytherapy [MD: 20 Gy], and 11 pts had EBPRT alone [MD: 50 Gy over 6 weeks].
      Group II: 246 pts received preoperative utero-vaginal brachytherapy [MD: 65 Gy],
      and 32 of theses 246 pts also received postoperative EBPRT [MD: 45 Gy over 5
      weeks] delivered to the parametric and the pelvic lymph nodes with a midline
      pelvic shield. The mean follow-up was 106 months. RESULTS: The 10-year disease
      free survival (DFS) rate was 80%. From 75 recurrences, 35 were isolated
      locoregional. Multivariate analysis showed that independent factors decreasing
      the probability of DFS were: both exo and endocervical tumour site (p = 0.047),
      lymph-vascular space invasion (p = 0.041), age < or = 51 yr (p = 0.013), 1995
      FIGO staging system (stage IB1 vs stage IIA, p = 0.004, stage IB1 vs stage IB2, p
      = 0.0009, and stage IB1 vs stage IIB with 1/3 proximal parametrical infiltration,
      p = 0.00002), and histological pelvic involved lymph nodes (p = 0.00009). Methods
      of adjuvant RT did not influence the probability of DFS (group I vs group II, p =
      0.10). The postoperative complication rate was 10.2% in group I and 8.9% in group
      II (p = 0.7) but the postoperative urethral complication rate necessitating
      surgical intervention with reimplantation was lower in group I than in group II
      (0.6% vs 2.3%, respectively, p = 0.03). The 10-year rate for grade 3 and 4 late
      radiation complications according to the LENT-SOMA scoring system was 10.4%. EPRT
      significantly increased the 10-year rate for grade 3 and 4 late radiation
      complications (yes vs no: 22% vs 7%, respectively, p = 0.0002). CONCLUSION: In
      our series, the methods of adjuvant RT (primary surgery vs preoperative
      uterovaginal brachytherapy) do not seem to influence the prognosis of the stage
      IB, IIA, and IIB (with 1/3 proximal parametrical involvement only) cervical
      carcinomas. The postoperative EPRT applied according to histopathological risk
      factors after surgical treatment increases the risk of late radiation
      complications.

PMID- 12224490
TI  - Race relations. A correct decision or a political one?

PMID- 12224489
TI  - ["Standards, Options and Recommendations 2001" for radiotherapy in patients with
      non-metastatic infiltrating breast cancer. Update. National Federation of Cancer
      Campaign Centers (FNCLCC)].
AB  - CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in
      1993, is a collaboration between the Federation of french cancer centers
      (FNCLCC), the 20 french cancer centers, and specialists from french public
      universities, general hospitals and private clinics. The main objective is the
      development of clinical practice guidelines to improve the quality of health care
      and the outcome of cancer patients. The methodology is based on a literature
      review and critical appraisal by a multidisciplinary group of experts, with
      feedback from specialists in cancer care delivery. OBJECTIVES: To develop
      clinical practice guidelines for non metastatic breast cancer patients according
      to the definitions of the Standards, Options and Recommendations project.
      METHODS: Data were identified by searching Medline, web sites, and using the
      personal reference lists of members of the expert groups. Once the guidelines
      were defined, the document was submitted for review to 148 independent reviewers.
      RESULTS: This article presents the chapter radiotherapy resulting from the 2001
      update of the version first published in 1996. The modified 2001 version of the
      standards, options and recommendations takes into account new information
      published. The main recommendations are: (1) Breast irradiation after
      conservative surgery significantly decrease the risk of local recurrence (level
      of evidence A) and the decrease in the risk of local recidive after chest wall
      irradiation is greater as the number of risk factors for local recurrence
      increases (level of evidence A). (2) After conservative surgery, a whole breast
      irradiation should be performed at a minimum dose of 50 Gy in 25 fractions
      (standard, level of evidence A). (3) A boost in the tumour bed should be
      performed in women under 50 years, even if the surgical margins are free
      (standard, level of evidence B). (4) Internal mammary chain irradiation is
      indicated for internal or central tumours in the absence of axillary lymph node
      involvement (expert agreement) and in the presence of lymph node involvement
      (standard, level of evidence B1). (5) Sub- and supra-claviculr lymph node
      irradiation is indicated in patients with axillary node involvement (standard,
      level of evidence B1).

PMID- 12224491
TI  - National Institute for Clinical Excellence. Eyeing up the experts.

PMID- 12224492
TI  - Cancer awareness. Dying of embarrassment.

PMID- 12224493
TI  - Should food adverts on children's television be banned?

PMID- 12224494
TI  - Cancer: the big picture.

PMID- 12224495
TI  - Gone, and all but forgotten.

PMID- 12224496
TI  - Caught in the crossfire.

PMID- 12224497
TI  - Setting standards for clinical care in Scotland.
AB  - The Clinical Standards Board for Scotland was set up to reassure the public that
      standards of care in the country's NHS were of the highest quality. This article
      describes the model adopted to write, assess and monitor national standards
      related to three key clinical priorities: cancer, coronary heart disease and
      mental health.

PMID- 12224498
TI  - Home chemotherapy: NHS and independent sector collaboration.
AB  - Current government health policy calls for increased collaboration between acute
      and primary care, and between the NHS and the independent sector. This article
      describes an initiative in which an NHS trust contracted an independent company
      to provide home chemotherapy for patients with cancer of the colon. Home-based
      therapy enables patients to choose the service that suits them most, and can
      reduce the stress associated with their disease and treatment. It has also been
      found to reduce the side-effects of treatment. This article includes a case study
      on a patient receiving home chemotherapy which illustrates some of the benefits
      of the service for patients.

PMID- 12224499
TI  - Giving students the confidence to take part.
AB  - This article discusses whether nursing students can gain confidence and become
      accepted as members of the team in their first clinical placement. The topic
      emerged from a study looking at the experiences of a cohort of diploma-level
      nursing students undertaking a general training programme. Six 45-minute
      interviews were conducted in a large teaching hospital in Dublin. The results
      indicated that by demonstrating procedures repeatedly nurses can accelerate a
      student's ability to become a productive member of the ward team.

PMID- 12224500
TI  - Improving care for people with learning disabilities.
AB  - In November 1998, a project group began a review of acute hospital service
      provision in Sheffield for people with learning disabilities and their carers.
      The aim was to produce recommendations for future development. Throughout the
      project, patients with learning disabilities and their carers were consulted
      along with professionals and focus groups representing people with learning
      disabilities. The project group identified the need for new audit tools and
      integrated care pathways, changes to documentation and working practices, as well
      as the need to develop training. The group presented its findings to the
      executive of the newly formed Sheffield Teaching Hospitals NHS Trust, which gave
      full support for the group's recommendations to be implemented throughout the
      trust.

PMID- 12224501
TI  - Special focus on. Chronic obstructive pulmonary disease.

PMID- 12224502
TI  - Day in the life.

PMID- 12224503
TI  - Strategies for the identification and analysis of viral immune-evasive genes-
      cytomegalovirus as an example.
AB  - Co-evolution of herpesviruses with their hosts has resulted in multiple
      interactions between viral genes and cellular functions. Some interactions
      control genomic maintenance and replication in specific tissues, other affect the
      immune control at various stages. Few immunomodulatory functions of genes can be
      predicted by sequence homology. The majority of genes with immunomodulatory
      properties only become apparent in functional assays. This chapter reviews
      procedures which have been used for successful identification of immunomodulatory
      genes in the past and deals with recent methods which may be applicable for the
      identification of additional immunomodulatory functions unknown so far.

PMID- 12224505
TI  - Viral evasion of natural killer cells during human cytomegalovirus infection.
AB  - Cytotoxic T cells are major players in the immune defence against human
      cytomegalovirus (HCMV). The virus has, however, developed several mechanisms to
      escape from this control. In particular, it down-regulates cell surface
      expression of HLA class I molecules. Because natural killer (NK) cells recognize
      and eliminate cells that lack HLA class I molecules, HCMV-infected cells could be
      more susceptible to NK lysis. In this review, we discuss the role played by NK
      cells in immune defence against HCMV and we describe potential strategies the
      virus has developed to escape from NK cell-mediated lysis. We focus in particular
      on a newly described protein, HCMV gpUL40, that induces cell surface expression
      of HLA-E, a non-classical class I molecule known to regulate NK cell functions.

PMID- 12224504
TI  - Inhibition of the MHC class II antigen presentation pathway by human
      cytomegalovirus.
AB  - Human cytomegalovirus (HCMV) causes serious disease in immunocompromised
      individuals. Normally, anti-HCMV immune response controls virus replication
      following reactivation from latency. However, HCMV, like other large
      herpesviruses, encodes immune evasion proteins that allow the virus to replicate,
      for a time or in specific tissues, and produce viral progeny in the face of
      robust host immunity. HCMV glycoproteins US2, US3, US6 and US11 all inhibit
      different stages of the MHC class I antigen presentation pathway and can reduce
      recognition by CD8+ T lymphocytes. Here, we discuss two novel inhibitors of the
      MHC class II antigen presentation pathway, HCMV glycoproteins US2 and US3. Both
      US2 and US3 can inhibit presentation of exogenous protein antigens to CD4+ T
      lymphocytes in in vitro assays. US2 causes degradation of MHC class II molecules:
      HLA-DR-alpha and HLA-DM-alpha, as well as class I heavy chain (HC), but does not
      affect DR-beta or DM-beta chains. Mutant forms of US2 have been constructed that
      can bind to DR-alpha and class I HC but do not cause their degradation,
      separating the binding step from other processes that precede degradation. We
      also found evidence that US2-induced degradation of class I and II proteins
      involves a cellular component, other than Sec61, that is limiting in quantity.
      Unlike US2, US3 binds newly synthesized class II alpha/beta complexes, reducing
      the association with the invariant chain (Ii) and causing mislocalization of
      class II complexes in cells. US3 expression reduces accumulation of class II
      complexes in peptide-loading compartments and loading of peptides. Since US2 and
      US3 are expressed solely within HCMV-infected cells, it appears that these viral
      proteins have evolved to inhibit presentation of endogenous, intracellular viral
      antigens to anti-HCMV CD4+ T cells. This is different from how the MHC class II
      pathway is normally viewed, as a pathway for presentation of exogenous,
      extracellular proteins. The existence of these proteins indicates the importance
      of class II-mediated presentation of endogenous antigens in signalling virus
      infection to CD4+ T cells.

PMID- 12224506
TI  - Function of CMV-encoded MHC class I homologues.
AB  - Homologues of MHC class I proteins have been identified in the genomes of human,
      murine and rat cytomegaloviruses (CMVs). Given the pivotal role of the MHC class
      I protein in cellular immunity, it has been postulated that the viral homologues
      subvert the normal antiviral immune response of the host, thus promoting virus
      replication and dissemination in an otherwise hostile environment. This review
      focuses on recent studies of the CMV MHC class I homologues at the molecular,
      cellular and whole animal level and presents current hypotheses for their roles
      in the CMV life cycle.

PMID- 12224507
TI  - Human cytomegalovirus inhibition of major histocompatibility complex
      transcription and interferon signal transduction.
AB  - Pathogens have evolved diverse mechanisms for escaping host innate and adaptive
      immunity. Viruses that maintain a persistent infection are particularly effective
      at disabling key arms of the host immune response. For example, the herpesviruses
      establish a persistent infection in human and animal hosts, in part through
      critical immunoevasive strategies. Cytomegalovirus, a beta-herpesvirus, impairs
      major histocompatibility complex (MHC) class I and class II antigen presentation
      by decreasing MHC expression on the surface of the infected cell, thus enabling
      infected cells to escape CD8+ and CD4+ T lymphocyte immunosurveillance. Moreover,
      cytomegalovirus blocks the interferon signal transduction pathway, thereby
      limiting the direct and indirect antiviral effects of the interferons. In this
      review, we focus on an emerging paradigm in which the effectiveness of viruses,
      particularly human cytomegalovirus, to escape antiviral immune responses is
      significantly enhanced by their ability to inhibit MHC transcription and
      interferon (IFN)-stimulated (JAK/STAT) signal transduction.

PMID- 12224508
TI  - Counteraction of interferon-induced antiviral responses by herpes simplex
      viruses.
AB  - The outcome of a viral infection of a host involves the complex interplay of
      viral determinants of virulence and host resistance factors. Among the first
      lines of defense for the host in attempts to control viral infection are the
      interferons (IFNs). A large body of work has now shown that the IFNs are a family
      of soluble proteins that serve to mediate antiviral effects, to regulate cell
      growth, and to modulate the activation of immune responses. The innate antiviral
      activities of IFNs are exceedingly potent and rapid. It is, therefore, not
      surprising that so many viruses have evolved ways to either preclude the
      synthesis of IFNs or evade downstream antiviral events. Such evasion allows for
      the virus to spread before the development of a specific adaptive immune response
      and likely represents a pivotal determinant of virulence for the invading virus.
      This review describes some of the research on herpes simplex virus (HSV) that has
      elucidated genes involved in evasion of the IFN response. In particular, the
      roles of specific viral genes in resistance to the antiviral effects of PKR and
      RNaseL are described, along with other HSV genes and loci associated with
      resistance to IFN for which mechanisms have yet to be described.

PMID- 12224509
TI  - Immune evasion strategies of Kaposi's sarcoma-associated herpesvirus.
AB  - To establish lifelong infection in the presence of an active host immune system,
      herpesviruses have acquired an impressive array of immune modulatory mechanisms
      that contribute to their success as long-term parasites. Kaposi's sarcoma
      associated herpesvirus (KSHV) is the most recently discovered human tumor virus
      and is associated with the pathogenesis of Kaposi's sarcoma, primary effusion
      lymphoma, and multicentric Castleman's disease. KSHV has acquired a battery of
      genes to assist in viral survival against the host immune response. These viral
      gene products target a variety of host immune surveillance mechanisms, including
      the cytokine-mediated immune response, apoptosis, natural killer (NK) cell
      killing and T cell-mediated responses. This review summarizes our understanding
      of the role of these viral proteins in the escape from host immune surveillance,
      which ultimately contributes to lifelong infection and pathogenesis of KSHV.

PMID- 12224510
TI  - Viral chemokine receptors and chemokines in human cytomegalovirus trafficking and
      interaction with the immune system. CMV chemokine receptors.
AB  - The ubiquitous, opportunistic pathogen human cytomegalovirus (CMV) encodes
      several proteins homologous to those of the host organism. Four different CMV
      genes encode chemokine receptor-like peptides. These genes, UL33, UL78, US27, and
      US28, are expressed at various stages of infection in vitro. Their functions
      remain largely unknown. To date, chemokine binding and signalling has only been
      demonstrated for the US28 gene product. Putative ligands for the other CMV
      encoded chemokine receptors are discussed on basis of phylogenetic analysis. The
      potential roles of these receptors in virus trafficking, persistence, and immune
      evasion are summarized. Similarly, modulation of expression of the host
      chemokines IL-8, MCP-1a and RANTES in relation to viral dissemination and
      persistence is reviewed.

PMID- 12224511
TI  - Avoiding proteasomal processing: the case of EBNA1.
AB  - Ubiquitin/proteasome-dependent proteolysis is involved in the regulation of a
      large variety of cellular processes including cell cycle progression, tissue
      development and atrophy, flux of substrates through metabolic pathways, selective
      elimination of abnormal proteins and processing of intracellular antigens for
      major histocompatibility complex (MHC) class I-restricted T-cell responses. Many
      viruses tamper with this proteolytic machinery by encoding proteins that interact
      with various components of the pathway. A particularly interesting example of a
      viral protein that interferes with proteasomal processing is the Epstein-Barr
      virus (EBV) nuclear antigen-1 (EBNA1). EBNA1 contains an internal repeat
      exclusively composed of glycines and alanines that inhibits in cis the
      presentation of MHC class I-restricted T-cell epitopes and prevents
      ubiquitin/proteasome-dependent proteolysis in vitro and in vivo. The glycine
      alanine repeat acts as a transferable element on a variety of proteasomal
      substrates and may therefore provide a new approach to the modification of
      cellular proteins for therapeutic purposes.

PMID- 12224512
TI  - Fatal attraction: cytomegalovirus-encoded chemokine homologs.
AB  - Members of the cytomegalovirus (CMV) subfamily of betaherpesviruses infecting
      primates and rodents encode divergent proteins with sequence characteristics and
      activities of chemokines, a class of small, secreted proteins that control
      leukocyte migration and trafficking behavior. Human CMV genes UL146 and UL147
      encode proteins with sequence characteristics of CXC chemokines, whereas, murine
      CMV encodes a CC chemokine homolog (MCK-2). Human CMV UL146 encodes a neutrophil
      attracting chemokine denoted viral CXC chemokine-1 (vCXCL1) that is as potent as
      host IL-8 and functions via the CXCR2 receptor, one of two human IL-8 receptors.
      Murine CMV MCK-2 is composed of a chemokine domain derived from open reading
      frame (ORF) m131 (and denoted MCK-1) as well as a domain derived from m129 that
      does not have sequence similarity to any known class of proteins. A synthetic
      version of murine CMV m131 (MCK-1) protein carries out many of the activities of
      a positive-acting chemokine, including transient release of intracellular calcium
      stores and cell adhesion of peritoneal macrophage populations. In the context of
      the viral genome and infection of the mouse host, the m131-m129 (MCK-2) gene
      product confers increased inflammation, higher levels of viremia, and higher
      titers of virus in salivary glands, consistent with a role in promoting
      dissemination by attracting an important mononuclear leukocyte population. Other
      characterized primate CMVs, but not other primate betaherpesviruses, encode gene
      products similar to human UL146 and UL147. Other characterized rodent CMVs encode
      a gene product similar to the murine CMV chemokine homolog, although not as a
      spliced gene product. Thus chemokines, like viral proteins that downmodulate MHC
      class I expression or have sequence homology to host MHC class I proteins, have
      evolved in primate and rodent CMVs to carry out an analogous set of
      immunomodulatory functions during infection of the host even though they arise
      from distinct origins.

PMID- 12224513
TI  - Herpesviral proteins regulating apoptosis.
AB  - The induction of apoptosis of virus-infected cells is an important defense
      mechanism of the host. Apoptosis of an infected cell can be induced cell
      autonomously as a consequence of viral replication or can be mediated by CTLs
      attacking the infected cells. Herpesviruses have developed different strategies
      to interfere with cell-autonomous apoptosis and to block CTL-induced apoptosis
      mediated by death receptors such as Fas and TRAIL. Herpesviruses, which establish
      a lifelong persistence in the infected host, can be found principally in two
      different conditions, episomal persistence with a limited number of genes
      expressed and lytic replication with expression of almost all genes. To meet the
      need of the virus to enhance survival of the infected cell, herpesviruses have
      evolved different strategies that function during both episomal persistence and
      lytic replication. Herpesviruses, which encode 70 to more than 200 genes have
      incorporated cell homologous antiapoptotic genes, they code for multifunctional
      genes that can also regulate apoptosis, and, finally, they modulate the
      expression of cellular apoptosis-regulating genes to favor survival of the
      infected cells. Viral interference with host cell apoptosis enhances viral
      replication, facilitates virus spread and persistence, and may promote the
      development of virus-induced cancer.

PMID- 12224514
TI  - Subversion of host defense mechanisms by adenoviruses.
AB  - Adenoviruses (Ads) cause acute and persistent infections. Alike the much more
      complex herpesviruses, Ads encode numerous immunomodulatory functions. About a
      third of the viral genome is devoted to counteract both the innate and the
      adaptive antiviral immune response. Immediately upon infection, E1A blocks
      interferon-induced gene expression and the VA-RNA inhibits interferon-induced PKR
      activity. At the same time, E1A reprograms the cell for DNA synthesis and induces
      the intrinsic cellular apoptosis program that is interrupted by E1B/19K and
      E1B/55K proteins, the latter inhibits p53-mediated apoptosis. Most other viral
      stealth functions are encoded by a separate transcription units, E3. Several E3
      products prevent death receptor-mediated apoptosis. E3/14.7K seems to interfere
      with the cytolytic and pro-inflammatory activities of TNF while E3/10.4K and
      14.5K proteins remove Fas and TRAIL receptors from the cell surface by inducing
      their degradation in lysosomes. These and other functions that may afect granule
      mediated cell death might drastically limit lysis by NK cells and cytotoxic T
      cells (CTL). Moreover, Ads interfere with recognition of infected cell by CTL.
      The paradigmatic E3/19K protein subverts antigen presentation by MHC class I
      molecules by inhibiting their transport to the cell surface. In concert, these
      viral countermeasures ensure prolonged survival in the infected host and, as a
      consequence, facilitate transmission. Elucidating the molecular mechanisms of Ad
      mediated immune evasion has stimulated corresponding research on other viruses.
      This knowledge will also be instrumental for designing better vectors for gene
      therapy and vaccination, and may lead to a more rational treatment of life
      threatening Ad infections, e.g. in transplantation patients.

PMID- 12224515
TI  - The HCMV gene products US2 and US11 target MHC class I molecules for degradation
      in the cytosol.
AB  - Over millions of years of coevolution with their hosts, viruses have developed
      highly effective strategies to elude the host immune system. The degradation of
      major histocompatibility complex (MHC) class I heavy chains by human
      cytomegalovirus (HCMV) is an example of this. Two HCMV proteins, US2 and US11,
      target newly synthesized MHC class I heavy chains for destruction via a pathway
      that involves ubiquitin-dependent retrograde transport, or "dislocation", of the
      heavy chains from the ER to the cytosol, where the proteins are degraded by
      proteasomes. In this review, US2- and US11-mediated degradation of MHC class I
      heavy chains is discussed in relation to data concerning the degradation of other
      ER luminal proteins. A new, unified model for translocon-facilitated dislocation
      and degradation of MHC class I heavy chains is presented.

PMID- 12224516
TI  - Corking the bottleneck: the transporter associated with antigen processing as a
      target for immune subversion by viruses.
AB  - In this chapter, mechanisms are reviewed that viruses use to inhibit the function
      of the peptide transporter associated with antigen processing (TAP), which
      translocates cytosolic peptides into the endoplasmic reticulum (ER) for binding
      to MHC class I molecules. Although some DNA viruses, such as adenovirus or EBV,
      downmodulate TAP expression on the transcriptional level, members of the alpha
      and beta subfamily of herpesviruses, such as herpes simplex virus (HSV) and human
      cytomegalovirus (HCMV), express proteins that bind to TAP and interfere with
      peptide translocation. The modes of action of the HSV-encoded cytosolic TAP
      inhibitor ICP47 and the HCMV-encoded ER-resident TAP inhibitor gpUS6 are
      discussed in detail. Viral interference with antigen presentation through TAP
      inhibition is not only relevant for the immunobiology of persistent viral
      infections but also contributes to the understanding of the translocation
      mechanism utilized by the ATP-binding cassette transporter TAP.

PMID- 12224517
TI  - Herpes viral proteins manipulating the peptide transporter TAP.
AB  - The peptide transporter associated with antigen processing (TAP) is crucial for
      class I-restricted antigen presentation because it transfers cytosolic peptides
      into the endoplasmic reticulum (ER) lumen for class I binding. It is therefore
      not surprising that TAP is targeted for inactivation by many viruses.
      Herpesviruses have been very successful in designing various proteins that
      inactivate TAP. We summarise current knowledge on the class I antigen
      presentation pathway and the function, structure and action of TAP and its viral
      inhibitors.

PMID- 12224518
TI  - Herpes viral proteins blocking the transporter associated with antigen processing
      TAP--from genes to function and structure.
AB  - In adaptation to the immune system, viruses have developed manifold mechanisms to
      evade the immune response, causing lifelong persistence in the host. Several
      members of the herpesvirus family are known to interfere with antigen
      presentation via MHC class I molecules. Here we compare the mechanistic and
      structural aspects of two unrelated herpesviral proteins, both of which have
      selected the transporter associated with antigen processing (TAP) as target for
      immune evasion. However, ICP47 (IE12) encoded by the herpes simplex virus and US6
      from human cytomegalovirus utilize entirely different strategies to block TAP
      function. Detailed knowledge of the function and structure of these viral factors
      will help to understand TAP function and to design novel immune suppressors or
      vectors for gene transfer.

PMID- 12224519
TI  - Introduction: anthrax history, disease and ecology.
AB  - The familiarity with the ancient disease anthrax from the second millennium B.C.
      through the second millennium A.D. is reviewed, providing the backdrop to the
      modern understanding of this disease as covered in the remainder of the volume.
      By means of an overview of the aetiology, ecology, epidemiology, clinical
      manifestations, pathology and bacteriology of the naturally acquired disease,
      this opening chapter also lays down the groundwork for the subsequent state-of
      the-art chapters.

PMID- 12224520
TI  - Macrophage interactions.
AB  - B. anthracis virulence is the sum of the contributions of factors involved in
      toxicity, growth and persistence in the host. Recent data has revealed that the
      interactions between B. anthracis and macrophage is central to the B. anthracis
      pathogenesis. This review presents and describes tactics by which B. anthracis
      not only overcomes and avoids macrophages but also perverts the host defense
      immune system and defense-related products to its advantage. The understanding of
      the complex network of such interactions is likely to allow new therapeutic and
      preventative strategies to be developed.

PMID- 12224521
TI  - Bacillus anthracis genetics and virulence gene regulation.
AB  - The Bacillus anthracis genome consists of an approximately 5.3-Mb chromosome and
      two plasmids, pXO1 (182 kb) and pXO2 (96 kb). Genetic analysis has focused
      primarily on the structural genes for the anthrax toxin proteins, pagA, lef, and
      cya, the biosynthetic genes for capsule synthesis, capB, capC, and capA, and a
      gene associated with depolymerization of capsule, dep. The three toxin genes are
      located at distinct loci on pXO1, while the cap and dep genes are arranged in an
      apparent operon on pXO2. Additional genes that may play a role in B. anthracis
      virulence include the germination operon gerX and the general stress
      transcription factor sigB. Host-related signals affecting transcription of the
      toxin and capsule genes include temperature (37 degrees C) and bicarbonate/CO2.
      The B. anthracis plasmids carry two regulatory genes that share little sequence
      similarity with regulators in other bacteria. The pXO1-encoded gene atxA
      positively controls expression of the toxin and capsule genes, and has been
      implicated in control of other genes of unknown function. atxA mutants are
      avirulent in mice, and mice infected with atxA-null strains show a decreased
      immunological response to the toxin proteins. The pXO2-encoded regulator, acpA,
      shares sequence similarity with atxA. Yet acpA function appears to be restricted
      to positive control of capsule gene expression. The chromosomal gene abrB, a
      homologue of a well-characterized B. subtilis transition state regulator,
      controls growth phase-specific transcription of the toxin genes. Genetic
      manipulation of B. anthracis can be achieved by using natural means of DNA
      transfer and by electroporation of recombinant DNAs into B. anthracis. Genetic
      exchange can occur between B. anthracis strains and between B. anthracis and
      closely-related species. Although pXO1 and pXO2 are not self-transmissible, these
      plasmids and others can be transferred by conjugative plasmids originating in B.
      thuringiensis. Generalized transducing phage that permit inter-species transfer
      of chromosomal and plasmid DNA have also been described.

PMID- 12224522
TI  - Bacillus anthracis evolution and epidemiology.
AB  - Bacillus anthracis is a pathogen that is widely distributed around the globe.
      However, this great distribution is not accompanied by great genetic diversity.
      Although subtle morphological and biochemical differences exist, the underlying
      genetic basis for this plasticity is not known. Indeed, very few single
      nucleotide differences have been detected among isolates and the only documented
      high variable sequences are associated with variable number tandem repeated
      (VNTR) sequences. The differences among the VNTRs has been used to suggest
      phylogenetic relationships among the worldwide isolates. There is one major
      clonal split in B. anthracis (A and B), with two minor clusters established
      within the B branch and four or more minor branches within the A group. The A
      branch is the most common worldwide, though the B branch is locally important in
      certain areas. The ecology and the evolution of B. anthracis have been greatly
      influenced by the spore phase of the lifecycle.

PMID- 12224524
TI  - Structure and function of anthrax toxin.
AB  - Anthrax toxin is a binary A-B toxin comprised of protective antigen (PA) and two
      enzymatic moieties, edema factor (EF) and lethal factor (LF). In the presence of
      a host cell-surface receptor, PA can mediate the delivery of EF and LF from the
      extracellular milieu into the host cell cytosol to effect toxicity. In this
      delivery, PA undergoes multiple structural changes--from a monomer to a
      heptameric prepore to a membrane-spanning heptameric pore. The catalytic factors
      also undergo dramatic structural changes as they unfold to allow for their
      translocation across the endosomal membrane and refold to preserve their
      catalytic activity within the cytosol. In addition to these gross structural
      changes, the intoxication mechanism depends on the ability of PA to form specific
      interactions with the host cell receptor, EF, and LF. This chapter presents a
      review of experiments probing these structural interactions and rearrangements in
      the hopes of gaining a molecular understanding of toxin action.

PMID- 12224523
TI  - Anthrax vaccines.
AB  - The only impetus for the development of new anthrax vaccines is to protect humans
      against the intentional use of Bacillus anthracis as a bioterrorist or warfare
      agent. Live attenuated vaccines against anthrax in domesticated animals were
      among the very first vaccines developed. This was followed by the development of
      nonliving component vaccines leading to the eventual licensure of protein-based
      vaccines for human use in the 1970s. This chapter will review the recent advances
      in developing protein, live attenuated, and genetic vaccines against anthrax.

PMID- 12224525
TI  - Bacillus anthracis cell envelope components.
AB  - Bacillus anthracis is a Gram-positive bacterium harboring a complex parietal
      architecture. The cytoplasmic membrane is surrounded by a thick peptidoglycan of
      the A1 gamma type. Only one associated polymer, a polysaccharide composed of
      galactose, N-acetylglucosamine, and N-acetylmannosamine, is covalently linked to
      the peptidoglycan. Outside the cell wall is an S-layer. Two proteins can each
      compose the S-layer. They are noncovalently anchored to the cell wall
      polysaccharide by their SLH N-terminal domain. The poly-gamma-D-glutamate
      capsule, which covers the S-layer, has an antiphagocytic role and its synthesis
      is dependent on environmental factors mimicking the mammalian host, such as
      bicarbonate and a temperature of 37 degrees C.

PMID- 12224526
TI  - Selenium-containing proteins in mammals and other forms of life.

PMID- 12224527
TI  - Chloroplast quest: a journey from the cytosol into the chloroplast and beyond.
AB  - Chloroplasts are characteristic organelles of plants and algae and the site of
      oxygenic photosynthesis. They are surrounded by a double membrane and possess an
      internal membrane system, the thylakoids, on which the photosynthetic machinery
      is located. They originated more than 1.2 billion years ago from an endosymbiotic
      event between an already photosynthetic ancestor of present day cyanobacteria and
      a mitochondriate host cell. During the transformation of the internalized
      cyanobacterium into a cell organelle most of the genetic information of the
      endosymbiot got lost or was transferred into the nucleus of the host. Chloroplast
      proteins encoded by nuclear genes are synthesized on cytoplasmic ribosomes and
      have to be relocated into the organelle. This is achieved by a proteinaceous
      import machinery in the outer and inner envelope of the chloroplasts. Proteins
      destined for the thylakoid membrane and the thylakoid lumen are further
      translocated by several different pathways into or across this membrane. The
      subject of this review is the quest of nuclear encoded chloroplast proteins into
      the organelle and to their final suborganellar location.

PMID- 12224528
TI  - Constitutively active and G-protein coupled inward rectifier K+ channels: Kir2.0
      and Kir3.0.

PMID- 12224529
TI  - Randomized clinical trial of Ligasure versus open haemorrhoidectomy.

PMID- 12224530
TI  - Immunohistochemical evidence of PTEN in oral squamous cell carcinoma and its
      correlation with the histological malignancy grading system.
AB  - PTEN is a tumor suppressor gene that encodes a dual phosphatase protein capable
      of modulating membrane receptors and interaction of the cell and extracellular
      stimuli. PTEN regulates cell physiology such as division,
      differentiation/apoptosis and also migration and adhesion. The expression of PTEN
      was evaluated by immunohistochemistry in OSCC and compared to a well-established
      histological malignancy grading system. The well-differentiated OSCC were 59.1%
      and poorly differentiated were 40.9%. According to PTEN expression, the cases
      were 45.5% positive (the entire tumor showed stained), 22.7% mixed (both negative
      and positive cells were present) and 31.8% negative (no staining was seen in the
      tumor cells). PTEN expression in OSCC was related to the malignancy grade (P <
      0.0005). Aggressive tumors with a high score of malignancy did not express PTEN,
      and clearly, the PTEN expression was present in the epithelium adjacent to the
      tumor. Negative cells were in the invasion border of the tumor. This result
      suggests that PTEN is related to histologic pattern and biological behavior of
      OSCC and may be a used as a prognostic marker in the future. The role of PTEN
      during carcinogenesis and as a biomarker should be further investigated.

PMID- 12224531
TI  - [ Sinusitis in children].

PMID- 12224532
TI  - Does warm weather climate affect eating disorder pathology?
AB  - OBJECTIVE: The aim of this study was to examine whether residing in a year-round
      warm weather climate is related to eating disorder pathology. METHOD: College
      females from a southeastern and a northeastern region of the United States were
      compared on body mass index, the Bulimia Test-Revised, the Body Shape
      Questionnaire, and the Body Image Avoidance Questionnaire. RESULTS: Females
      residing in the southeastern region were of significantly lower body weight,
      engaged in more frequent bulimic behaviors (e.g., bingeing and inappropriate
      compensatory behaviors), and displayed significantly greater concern regarding
      their body shape compared with the females residing in the northeastern region.
      DISCUSSION: Findings obtained in this study indicate that residing in a warm
      weather climate may produce a heightened risk for development of eating disorder
      pathology.

PMID- 12224533
TI  - Bibliography. Current world literature. Assessment of nutritional status and
      analytical methods.

PMID- 12224534
TI  - Bibliography. Current world literature. Carbohydrates.

PMID- 12224535
TI  - Commentary on: "Stereotyped activities produced by amphetamine in several animal
      species and man." Psychopharmacologia (1967) 11:300-310. A landmark publication
      from the early days of the dopamine hypothesis.

PMID- 12224536
TI  - On the anxiogenic and anxiolytic nature of long-term cerebral 5-HT depletion
      following MDMA.

PMID- 12224537
TI  - [Some thoughts].

PMID- 12224538
TI  - [Electric razors: avoid the risks!].

PMID- 12224542
TI  - [Microbial and immunological differences in patients using sharp versus cast
      dental bridges].

PMID- 12224543
TI  - Current awareness in NMR in biomedicine.

PMID- 12224544
TI  - JAMA patient page. Continuing medical education.

PMID- 12224545
TI  - Not such a featherbrain.

PMID- 12224546
TI  - SCHIP turns five: taking stock, moving ahead.
AB  - This issue brief notes the five-year anniversary of the effective date of Title
      XXI of the Social Security Act, the State Children's Health Insurance Program
      (SCHIP). It looks at the successes of the program, as well as some of the
      obstacles SCHIP will face as it moves from childhood into adolescence and
      attempts to maintain its effectiveness in providing health coverage to uninsured
      children and families. The paper explores the critical funding impasse created by
      the down turns in the economy and the financing structure of the SCHIP statute.
      It also highlights the emerging issue of program retention and the need to
      minimize unnecessary disenrollments. Finally, the issue brief considers the
      prospects for SCHIP's continued success-through bipartisan support in Congress
      and states' efforts to develop new and improved strategies to maintain and even
      expand their SCHIP programs in the coming years.

PMID- 12224547
TI  - Perikaryal surface specializations of neurons in sensory ganglia.
AB  - Slender projections, similar to microvilli, are the main specialization of the
      perikaryal surface of sensory ganglion neurons. The extent of these projections
      correlates closely with the volume of the corresponding nerve cell body. It is
      likely that the role of perikaryal projections of sensory ganglion neurons, which
      lack dendrites, is to maintain the surface-to-volume ratio of the nerve cell body
      above some critical level for adequate metabolic exchange. Satellite cells
      probably have the ability to promote, or provide a permissive environment for,
      the outgrowth of these projections. It is not yet known whether the effect of
      satellite cells is mediated by molecules associated with their plasma membrane or
      by diffusible factors. Furthermore, receptor molecules for numerous chemical
      agonists are located on the nerve cell body surface, but it is not known whether
      certain molecules are located exclusively on perikaryal projections or are also
      present on the smooth surface between these projections. Further study of the
      nerve cell body surface and of the influence that satellite cells exert on it
      will improve our understanding of the interactions between sensory ganglion
      neurons and satellite neuroglial cells.

PMID- 12224548
TI  - Biological aspects of signal transduction by cell adhesion receptors.
AB  - Cell adhesion receptors such as integrins, cadherins, selectins, and
      immunoglobulin family receptors profoundly modulate many signal transduction
      cascades. In this review we examine aspects of adhesion receptor signaling and
      how this impinges on key biological processes. We have chosen to focus on cell
      migration and on programmed cell death. We examine many of the cytoplasmic
      signaling molecules that interface with adhesion receptors, including focal
      adhesion kinase (FAK), phosphatidylinositol-3-kinase (PI3K), and elements of the
      Erk/MAP kinase pathway. In many cases these molecules impinge on both the
      regulation of cell movement and on control of apoptosis.

PMID- 12224549
TI  - Repressors of photomorphogenesis.
AB  - The internal programs of plant development are informed in a profound way by
      environmental light conditions. This review summarizes the contribution of
      repressor proteins to the light-signaling machinery during seedling development,
      and discusses the integration of repressors with other, positively acting, light
      signaling pathways and auxin and brassinosteroid hormone-signaling pathways. The
      main focus is placed on the mode of action of the COP/DET/FUS proteins, which
      were first identified in Arabidopsis but are now emerging in other plants. Their
      role in regulating protein turnover through ubiquitination is reviewed in light
      of parallel ongoing investigations of COP/DET/FUS homologues in metazoans and
      fungi.

PMID- 12224550
TI  - Vascular development in Arabidopsis.
AB  - Vascular tissues, xylem and phloem, form a continuous network throughout the
      plant body for transport of water, minerals, and food. Characterization of
      Arabidopsis mutants defective in various aspects of vascular formation has
      demonstrated that Arabidopsis is an ideal system for investigating the molecular
      mechanisms controlling vascular development. The processes affected in these
      mutants include initiation or division of procambium or vascular cambium,
      formation of continuous vascular cell files, differentiation of procambium or
      vascular cambium into vascular tissues, cell elongation, patterned secondary wall
      thickening, and biosynthesis of secondary walls. Identification of the genes
      affected by some of these mutations has revealed essential roles in vascular
      development for a cytokinin receptor and several factors mediating auxin
      transport or signaling. Mutational studies have also identified a number of
      Arabidopsis mutants defective in leaf venation pattern or vascular tissue
      organization in stems. Genetic evidence suggests that the vascular tissue
      organization is regulated by the same positional information that determines
      organ polarity.

PMID- 12224551
TI  - Acentrosomal microtubule nucleation in higher plants.
AB  - Higher plants have developed a unique pathway to control their cytoskeleton
      assembly and dynamics. In most other eukaryotes, microtubules are nucleated in
      vivo at the nucleation and organizing centers and are involved in the
      establishment of polarity. Although the major cytoskeletal components are common
      to plant and animal cells, which suggests conserved regulation mechanisms, plants
      do not possess centrosome-like organelles. Nevertheless, they are able to build
      spindles and have developed their own specific cytoskeletal arrays: the cortical
      arrays, the preprophase band, and the phragmoplast, which all participate in
      basic developmental processes, as shown by defective mutants. New approaches
      provide essential clues to understanding the fundamental mechanisms of
      microtubule nucleation. Gamma-tubulin, which is considered to be the universal
      nucleator, is the essential component of microtubule-nucleating complexes
      identified as gamma-tubulin ring complexes (gamma-TuRC) in centriolar cells. A
      gamma-tubulin small complex (gamma-TuSC) forms a minimal nucleating unit
      recruited at specific sites of activity. These components--gamma-tubulin, Spc98p,
      and Spc97p--are present in higher plants. They play a crucial role in microtubule
      nucleation at the nuclear surface, which is known as the main functional plant
      microtubule-organizing center, and also probably at the cell cortex and at the
      phragmoplast, where secondary nucleation sites may exist. Surprisingly, plant
      gamma-tubulin is distributed along the microtubule length. As it is not
      associated with Spc98p, it may not be involved in microtubule nucleation, but may
      preferably control microtubule dynamics. Understanding the mechanisms of
      microtubule nucleation is the major challenge of the current research.

PMID- 12224552
TI  - Interaction between endocrine and immune systems in fish.
AB  - Diseases in fish are serious problems for the development of aquaculture. The
      outbreak of fish disease is largely dependent on environmental and endogenous
      factors resulting in opportunistic infection. Recent studies, particularly on
      stress response, have revealed that bidirectional communication between the
      endocrine and immune systems via hormones and cytokines exists at the level of
      teleost fish. Recently information on such messengers and receptors has
      accumulated in fish research particularly at the molecular level. Furthermore, it
      has become apparent in fish that cells of the immune system produce or express
      hormones and their receptors and vice versa to exchange information between the
      two systems. This review summarizes and updates the knowledge on endocrine-immune
      interactions in fish with special emphasis on the roles of such mediators or
      receptors for their interactions.

PMID- 12224553
TI  - Endocytosis and the cytoskeleton.
AB  - In this review we describe the potential roles of the actin cytoskeleton in
      receptor-mediated endocytosis in mammalian cells and summarize the efforts of
      recent years in establishing a relationship between these two cellular functions.
      With molecules such as dynamin, syndapin, HIP1R, Abp1, synaptojanin, N-WASP,
      intersectin, and cortactin a set of molecular links is now available and it is
      likely that their further characterization will reveal the basic principles of a
      functional interconnection between the membrane cytoskeleton and the vesicle
      budding machinery. We will therefore discuss proteins involved in endocytic
      clathrin coat formation and accessory factors to control and regulate coated
      vesicle formation but we will also focus on actin cytoskeletal components such as
      the Arp2/3 complex, spectrin, profilin, and motor proteins involved in actin
      dynamics and organization. Additionally, we will discuss how phosphoinositides,
      such as PI(4,5)P2, small GTPases thought to control the actin cytoskeleton, such
      as Rho, Rac, and Cdc42, or membrane trafficking, such as Rab GTPases and ARF
      proteins, and different kinases may participate in the functional connection of
      actin and endocytosis. We will compare the concepts and different molecular
      mechanisms involved in mammalian cells with yeast as well as with specialized
      cells, such as epithelial cells and neurons, because different model organisms
      often offer complementary advantages for further studies in this thriving field
      of current cell biological research.

PMID- 12224554
TI  - [Effects of simulated body fluid flowing rate on bone-like apatite formation on
      porous calcium phosphate ceramics].
AB  - Objective. Bone-like apatite formation on the surface of calcium phosphate
      ceramics was believed to be the necessary step that new bone grows on the
      ceramics and to be relative to the osteoinductivity of the material. This study
      aimed at investigating the influence of the flow rate of simulated body fluid
      (SBF) (2 ml/min) in skeletal muscle upon the formation of bone-like apatite on
      porous calcium phosphate ceramics. Method. The dynamic condition was realized by
      controlling the SBF flowing in/out of the sample chamber of 100 ml. The flow rate
      of 2 ml/min is close to that in human muscle environment. The pH and inorganic
      ionic composition of SBF are close to those of human body fluid. Result. Bone
      like apatite formation was relatively easier to occur in static SBF than in
      dynamic SBF. Experiment with flowing SBF (dynamic SBF) is better in mimicking the
      living body fluid than static SBF. Conclusion. The results from dynamic SBF may
      more truly show the relation between apatite layer formation and osteoinduction
      in biomaterials than that from in vitro experiments before.

PMID- 12224555
TI  - Bed rail-related entrapment deaths.

PMID- 12224556
TI  - Disease management programs.

PMID- 12224557
TI  - A review of drinking-water-associated endotoxin, including potential routes of
      human exposure.
AB  - In the past decade efforts have been made to reduce the formation of harmful
      disinfection byproducts during the treatment and distribution of drinking water.
      This has been accomplished in part by the introduction of processes that involve
      the deliberate encouragement of indigenous biofilm growth in filters. In a
      controlled environment, such as a filter, these biofilms remove compounds that
      would otherwise be available as disinfection byproduct precursors or support
      uncontrolled biological activity in distribution systems. In the absence of
      exposure to chlorinated water, most biofilm bacteria are gram negative and have
      an outer layer that contains endotoxin. To date, outbreaks of waterborne
      endotoxin-related illness attributable to contamination of water used in
      hemodialysis procedures have been only infrequently documented, and occurrences
      linked to ingestion or through dermal abrasions could not be located. However, a
      less obvious conduit, that of inhalation, has been described in association with
      aerosolized water droplets. This review summarizes documented drinking-water
      associated incidents of endotoxin exposure attributable to hemodialysis and
      inhalation. Typical endotoxin levels in water and conditions under which
      substantial quantities can enter drinking water distribution systems are
      identified. It would appear that endotoxin originating in tap water can be
      inhaled but at present there is insufficient information available to quantify
      potential health risks.

PMID- 12224558
TI  - Survival of the rhizosphere-competent biocontrol strain Pseudomonas fluorescens
      NBRI2650 in the soil and phytosphere.
AB  - Pseudomonas fluorescens NBRI2650 was isolated after screening 360 bacterial
      strains from the rhizosphere of chickpea (Cicer arietinum L.) grown in fungal
      disease-suppressive field soil. The strain was selected because of its high
      rhizosphere competence and ability to inhibit the growth of Fusarium oxysporum
      f.sp. ciceri, Rhizoctonia bataticola, and Pythium sp. under in vitro conditions.
      Survival and colonization of NBRI2650 in the phytosphere of chickpea, cotton
      (Gossypium hirsutum L.), cucumber (Cucumis sativus L.), and tomato (Lycopersicon
      seculentum Mill.) were monitored using a chromosomally located rifampicin-marked
      mutant P. fluorescens NBRI2650R. The strain showed variable ability to invade and
      survive in the phytosphere of different plants. Chickpea was used as a tester
      plant for further work, as it was not invaded by NBRI2650R. The interaction
      between NBRI2650R and F oxysporum fsp. ciceri was studied by both light
      microscopy and scanning electron microscopy. The lysis of the fungal cell wall by
      NBRI2650R was clearly demonstrated. Treatment of the chickpea seeds with
      NBRI2650R in prerelease experiments in the greenhouse using disease-conducive
      field soils from Jhansi and Kanpur resulted in increased plant growth and did not
      result in any perturbation of the indigenous microbial community that inhabited
      the rhizosphere of chickpea compared with nonbacterized seeds. Direct
      fermentation of diluted NBRI2650R on vermiculite without the need of expensive
      fermentors offers a reliable process for manufacturing bacterial inoculants in
      developing countries. Under field conditions, the horizontal and vertical
      movement of NBRI2650R was restricted to 30 and 60 cm, respectively, and the
      strain could not survive in the field during the 7 months before the chickpea
      could be planted for next cropping season. Field trials conducted at Jhansi,
      Kanpur, and Pantnagar resulted in higher grain yield increase in the bacteria
      treated seed compared with the nonbacterized control. Seed and furrow treatment
      of the two chickpeas ('Radhey' and 'H-208') at Pantnagar resulted in
      significantly (P = 0.05) greater seedling mortality in nonbacterized seedlings
      compared with bacterized ones. The seed dry weight and yield for each variety
      were also significantly higher in bacterized seedlings than in nonbacterized
      ones. The population of NBRI2650R persisted throughout the growing season of
      chickpea in the range of 5.4-6.4 log10 CFU/g root.

PMID- 12224559
TI  - Actinobacillus actinomycetemcomitans genetic heterogeneity: amplification of JP2
      like ltx promoter pattern correlated with specific arbitrarily primed polymerase
      chain reaction (AP-PCR) genotypes from human but not marmoset Brazilian isolates.
AB  - Specific clonal types of Actinobacillus actinomycetemcomitans, a major human
      periodontal pathogen, may be responsible for clinical manifestations and the
      production of leukotoxin virulence factors. Leukotoxicity is associated with
      genetic polymorphism at the promoter region of the leukotoxin (lItx) gene. Here,
      we describe the use of arbitrarily primed polymerase chain reaction (AP-PCR) and
      ltx promoter PCR to molecularly characterise 35 A. actinomycetemcomitans
      Brazilian isolates: 21 of human origin and 14 from captive marmosets (Callitrix
      spp., primates commonly used as animal models for periodontal research). The
      discriminative capacity of each of 12 arbitrary primers was found to be variable,
      yielding between 3 and 24 PCR amplitypes. Combination of the results for all
      primers led to characterisation of 14 genotypes that grouped into four major
      clusters based on genetic similarity. Clusters 2, 3, and 4 were discriminative to
      host origin. A correlation with periodontal disease was suggested for strains
      belonging to clusters 3 and 4. The JP2-like PCR amplification pattern, associated
      with highly leukotoxic strains, was exclusive to human isolates and present in
      29% of human isolates where it occurred in close relationship with AP genotypes L
      and J (cluster 3).

PMID- 12224560
TI  - Bacterial diversity associated with subalpine fir (Abies lasiocarpa)
      ectomycorrhizae following wildfire and salvage-logging in central British
      Columbia.
AB  - To assess the effect of fire and salvage logging on the diversity of mycorrhizal
      bacterial communities, bacteria associated with Cenococcum, Thelephora,
      Tomentella, Russulaceae, and E-strain ectomycorrhizae (ECM) of Abies lasiocarpa
      seedlings were characterized using two approaches. First, bacteria were isolated
      and characterized by Biolog, gas chromatography fatty acid methyl ester (GC
      FAME), and amplified 16S rDNA restriction analysis (ARDRA). The bacterial
      communities retrieved from ECM from both sites were dominated by Proteobacteria
      (groups gamma and beta). Pseudomonas was the most common genus isolated, followed
      by Variovorax, Burkholderia, and Xanthomonas. Gram-positive isolates (mostly high
      G+C Gram-positive bacteria) were more frequently retrieved on the burned-salvaged
      site, many commonly associated with the two ascomycete ECM, Cenococcum and E
      strain. Pseudomonas species were retrieved more frequently from Thelephora.
      Although actinomycetes were isolated from all sites, almost no actinomycetes or
      other Gram-positive bacteria were isolated from either Thelephora or Tomentella.
      Second, amplified 16S rRNA gene sequences were amplified directly from root tips
      and then cloned into the plasmid vector pAMP1, followed by restriction analysis.
      This technique distinguished more genotypes than isolates retrieved by culturing
      methods, but generally, results were similar in that the largest proportion of
      the bacteria were putatively Gram-negative; putative Gram-positive bacteria were
      fewer and most were from the burned-salvaged site. Direct cloning resulted in
      many patterns that did not match any identified isolates, suggesting that a large
      proportion of clones were unique or not culturable by the methods used. Analysis
      for both protocols showed no significant difference in bacterial diversity
      between the burned-salvaged and unburned sites.

PMID- 12224561
TI  - The evaluation of mixtures of yeast and potato extracts in growth media for
      biomass production of lactic cultures.
AB  - The effectiveness of yeast extracts (YE) and potato extracts (PE) to promote
      growth of seven lactic cultures was evaluated by automated spectrophotometry
      (AS). Two aspects of the growth curve were analysed: (1) maximum biomass obtained
      (using ODmax) and (2) highest specific growth rate mu(max)) Eleven lots from the
      same PE-manufacturing process were examined for lot-to-lot variability. The ODmax
      values of three of the seven strains were significantly affected by lot source,
      but mu(max) was not significantly affected. The growth of bacteria was
      systematically lower in base medium containing 100% PE than in base medium
      containing 100% YE for both ODmax or mu(max) data, which could be related to the
      lower content in nitrogen-based compounds in PE. In AS assays, highest OD values
      for Lactobacillus casei EQ28, Lactobacillus rhamnosus R-011, Lactobacillus
      plantarum EQ12, and Streptococcus thermophilus R-083 were obtained with a mixture
      of PE and YE. Fermentations (2 L) were also carried out to determine the accuracy
      of AS to predict biomass levels obtained under fermentation trials. In these
      fermentations, replacement of 50% YE with PE was shown to enable good growth of
      S. thermophilus. With L. rhamnosus R-011, a high correlation (R2 = 0.95) was
      found between ODmax data obtained in the AS assays and that of the 2-L bioreactor
      when the same growth medium was used for both series of fermentations. However,
      AS was not as efficient when industrial media were used for the bioreactor
      assays. The relationship was still good for ODmax between AS data and that of the
      bioreactor data with L. rhamnosus R-011 in industrial LBS medium (R2 = 0.87), but
      was very poor with the S. thermophilus R-083 on Rosell #43 industrial medium (R2
      = 0.33). Since PE cost 40% less than YE, there are strong economic advantages in
      considering such a partial replacement of YE by PE.

PMID- 12224562
TI  - Regulation of indoleacetic acid production in Pseudomonas putida GR12-2 by
      tryptophan and the stationary-phase sigma factor RpoS.
AB  - The phytohormone indole-3-acetic acid (IAA) accumulates in the culture medium of
      the plant growth-promoting bacterium Pseudomonas putida GR12-2 only when grown in
      the presence of exogenous tryptophan, suggesting that expression of
      indolepyruvate decarboxylase, a key enzyme in the IAA biosynthesis pathway in
      this bacterium, may be regulated by tryptophan. To test this hypothesis, we
      isolated the promoter region for the ipdc gene encoding indolepyruvate
      decarboxylase by inverse polymerase chain reaction (PCR) and inserted it upstream
      of the bioluminescent reporter gene luxAB on a plasmid in P. putida GR12-2.
      Activity of the ipdc promoter, measured by quantifying light production,
      increased fivefold in the presence of L-tryptophan, confirming that ipdc
      expression is induced by tryptophan. In addition, transcription of ipdc is
      regulated by the stationary phase sigma factor RpoS: the ipdc promoter contains a
      sequence similar to the RpoS recognition sequence, and transformation of P.
      putida GR12-2 with a plasmid carrying rpoS under the control of a constitutive
      promoter induced promoter activity before the onset of stationary phase when RpoS
      is not normally produced and prolonged a higher level of transcription at the
      later stages of the cell cycle.

PMID- 12224563
TI  - Cultivation-dependent characterization of bacterial diversity from British
      Columbia forest soils subjected to disturbance.
AB  - Bacteria from forest surface organic matter and mineral soil horizons were
      cultivated using four methods and characterized by fatty acid methyl ester (FAME)
      analysis. Soil samples from a British Columbia Ministry of Forests Long-Term Soil
      Productivity (LTSP) installation were collected during winter and summer from two
      disturbance treatments (whole-tree harvesting with no soil compaction (plot N)
      and whole-tree harvesting plus complete surface organic matter removal with heavy
      soil compaction (plot S)) and from an unlogged reference plot (REF). Seventy-five
      percent of 1795 bacterial isolates were affiliated with 42 genera representing
      beta- and gamma-Proteobacteria, Actinobacteria, the Bacillus/Clostridium group,
      and the Cytophaga-Flexibacter-Bacteroides group. Approximately half of the
      culture collection represented genetic diversity confined to four bacterial
      genera: Pseudomonas, Bacillus, Paenibacillus, and Arthrobacter. A significantly
      higher proportion of bacterial isolates belonging to Actinobacteria, and the
      member genus Arthrobacter, were isolated from plot S soil samples compared with
      soil samples from plots N and REF. Twenty-five percent of bacterial isolates were
      not conclusively identified to genus with FAME analysis. Sherlock Tracker cluster
      analysis and partial 16S rRNA gene sequence analysis enabled classification of a
      subset of these isolates.

PMID- 12224564
TI  - Molecular characterization of bacterial diversity from British Columbia forest
      soils subjected to disturbance.
AB  - Bacteria from forest soils were characterized by DNA sequence analysis of cloned
      16S rRNA gene fragments (16S clones). Surface organic matter and mineral soil
      samples from a British Columbia Ministry of Forests Long-Term Soil Productivity
      (LTSP) installation were collected during winter and summer from two disturbance
      treatments: whole-tree harvesting with no soil compaction (plot N) and whole-tree
      harvesting plus complete surface organic matter removal with heavy soil
      compaction (plot S). Phylogenetic analyses revealed that 87% of 580 16S clones
      were classified as Proteobacteria, Actinobacteria, Acidobacterium,
      Verrucomicrobia, Bacillus/Clostridium group, Cytophaga-Flexibacter-Bacteroides
      group, green nonsulfur bacteria, Planctomyces, and candidate divisions TM6 and
      OP10. Seventy-five 16S clones could not be classified into known bacterial
      divisions, and five 16S clones were related to chloroplast DNA. Members of
      Proteobacteria represented 46% of the clone library. A higher proportion of 16S
      clones affiliated with y-Proteobacteria were from plot N compared with plot S.
      16S rRNA gene fragments amplified with Pseudomonas-specific primers and cloned
      (Ps clones) were examined from mineral-soil samples from plots N and S from three
      LTSP installations. A significantly greater proportion of sequenced Ps clones
      from plot N contained Pseudomonas 16S rRNA gene fragments compared with Ps clones
      from plot S.

PMID- 12224565
TI  - The stringent response genes relA and spoT are important for Escherichia coil
      biofilms under slow-growth conditions.
AB  - In order to see whether the stringent response was involved in biofilm formation,
      Escherichia coli DS291 (MG1655), and its isogenic relA spoT derivative were grown
      for 48 h in a chemostat at dilution rates of 0.025 and 0.25 h(-1) under serine
      limitation. The absence of the stringent response genes relA and spoT had little
      effect on the planktonic cell concentrations. However, a significant (P < 0.001)
      reduction in biofilm cell density of the relA spoT mutants was seen at a doubling
      time of 40 h. At a doubling time of 4 h, differences in biofilm cell density were
      not significant. Scanning confocal laser microscopy demonstrated the cell
      densities of microcolonies in the relA spoT mutant to be lower than those in the
      wild type. Using a microtiter plate assay, we found biofilm formation in relA
      spoT mutants to be similarly reduced in minimal media but to be enhanced in rich
      media (Luria-Bertani broth). No significant differences in biofilm formation were
      observed between wild type and isogenic relA mutants under any growth conditions.
      Overall, these results suggest that both stringent response genes relA and spoT
      are important in nutrient-limited biofilms.

PMID- 12224566
TI  - Asymptomatic Plasmodium parasitemia and the ecology of malaria transmission.

PMID- 12224567
TI  - High prevalence of asymptomatic Plasmodium vivax and Plasmodium falciparum
      infections in native Amazonian populations.
AB  - The epidemiology of malaria in 2 riverine localities in Rondjnia, Brazilian
      western Amazjnia, was assessed by a 1-year study at Portuchuelo, and a cross
      sectional survey at riverine communities at Rio Machado (= Ji-Parana). Plasmodium
      spp. infections were diagnosed by light microscopy and by polymerase chain
      reaction (PCR) amplification of ribosomal DNA. PCR was 6-7 times more efficient
      than microscopy for detecting plasmodial infections. Both Plasmodium vivax and
      Plasmodium falciparum infections occurred as asymptomatic and symptomatic forms
      of the disease. The relation between symptomatic and asymptomatic clinical forms
      was roughly similar for both species of Plasmodium. Symptomless patients were
      monitored for 2 months. The prevalence of symptomless infections was 4-5 times
      higher than the symptomatic ones--respectively, 20% and 4.6% for Portuchuelo and
      49.5% and 10% for Ji-Parana. Symptomatic malaria occurred mostly in patients in
      younger age groups. In contrast, there was a significant association of
      symptomless malaria with older age groups (medians of 26.5 and 21 years,
      respectively, for Portuchuelo and Ji-Parana), whereas the age medians for
      symptomatic malaria were 14 and 8 years, respectively, in the 2 regions.
      Symptomatic malaria also was more prevalent in groups living for shorter times in
      Amazjnia (13 and 4 years, respectively, for Portuchuelo and Ji-ParanA) as
      compared with symptomless malaria, which was more prevalent in groups living for
      longer periods in the region (medians of 25.5 and 18 years, respectively, for
      Portuchuelo and Ji-Parana). The high prevalence of symptomless malaria may pose
      new problems for the currently adopted strategy for the control of malaria in the
      Amazonian region, which is essentially based on the treatment of symptomatic
      patients.

PMID- 12224568
TI  - Assessing the Parasight-F test in northeastern Papua, Indonesia, an area of mixed
      Plasmodium falciparum and Plasmodium vivax transmission.
AB  - User-friendly, reliable, and inexpensive methods for diagnosing malaria are
      needed at the primary health care level. During a randomized treatment trial, the
      Parasight-F test was assessed on days 0, 3, 7, and 28 against standard light
      microscopy of Giemsa-stained thick blood smears for diagnosing Plasmodium
      falciparum parasitemia in patients with P. falciparum (n = 84) or P. vivax (n =
      59) malaria. The median P. falciparum parasite count on day 0 was 2,373/microL
      (range = 20-74,432/microL). At the start of treatment, the Parasight-F test had a
      sensitivity of 95.2% (80 of 84; 95% confidence interval [CI] = 88.2-98.7), and a
      specificity of 94.9% (56 of 59; 95% CI = 85.8-98.9). On day 7, this test showed
      false-positive results in 17 (16.3%) of 104 patients (95% CI = 9.8-24.9). The
      Parasight-F test performed well when compared with light microscopy in detecting
      P. falciparum parasitemia in patients presenting with clinical malaria. However,
      the high false-positive rate on day 7 limits its use for patient follow-up.

PMID- 12224569
TI  - New emerging Plasmodium falciparum genotypes in children during the transition
      phase from asymptomatic parasitemia to malaria.
AB  - Semi-immunity against Plasmodium falciparum occurs after many infections. In
      areas of high malaria transmission, the prevalence of asymptomatic parasite
      carriers increases with age. We investigated P. falciparum genotypes in a cohort
      of asymptomatic carriers who were followed until they became symptomatic. Blood
      spots on filter paper and blood smears were collected daily from 10 children in
      Lambarene, Gabon. The parasite genotypes present on successive days were
      determined by a polymerase chain reaction using the polymorphic region of the
      merozoite surface antigen-2 for typing. The same parasite genotypes persisted in
      eight out of ten children and parasite densities were low throughout the
      asymptomatic phase indicating inhibition of parasite growth. Appearance of
      symptoms was associated with an increase in parasitemia and appearance of novel
      parasite genotypes. The results suggest that the parasites causing a clinical
      episode are those against which a child has not yet mounted an efficient
      protective immune response.

PMID- 12224570
TI  - Short report: therapeutic efficacy of chloroquine combined with primaquine
      against Plasmodium falciparum in northeastern Papua, Indonesia.
AB  - Chloroquine combined with primaquine was evaluated for therapy of uncomplicated
      malaria caused by Plasmodium falciparum in nonimmune Javanese migrants to
      northeastern Papua, Indonesia. Subjects were randomized to treatment with
      standard chloroquine therapy (25 mg/kg in 3 doses over the course of 48 hours)
      with 30 mg primaquine administered daily for 28 days (n = 25) or a placebo of
      primaquine (n = 28). The 14-day cumulative incidence of therapeutic failure was
      56% with primaquine and 79% with placebo (odds ratio [OR], 0.35; 95% confidence
      interval [CI], 0.1-1.3; P = 0.08). Primaquine administered daily created a
      marginally significant improvement in therapeutic efficacy at day 14, but not at
      day 7 (20% versus 36%; OR, 0.2; 95% CI, 0.1-1.8; P = 0.2) or day 28 (82% versus
      93%; OR, 0.31; 95% Cl, 0.04-2.1; P = 0.23). This report corroborates studies
      suggesting that therapeutic doses of primaquine exert no discernible effect on
      parasitemia by P. falciparum.

PMID- 12224571
TI  - In vitro reversal of chloroquine resistance in Plasmodium falciparum with
      dihydroethanoanthracene derivatives.
AB  - The effects of combining four dihydroethanoanthracenic (DEA) derivatives and
      chloroquine were assessed in vitro against Plasmodium falciparum chloroquine
      resistant parasites W2, Palo Alto, FCR3, and Bres1. Like verapamil or
      promethazine, the four dihydroethanoanthracenic derivatives tested can be added
      to the growing list of agents that show capability in enhancing the activity of
      chloroquine against resistant parasites. The structurally related tricyclic
      antihistaminic compounds examined in this study exerted different intrinsic
      antimalarial activity, but the same chloroquine-potentiating activity as
      verapamil or promethazine. They may act both on the rate of chloroquine
      accumulation and on its access to ferriprotoporphyrin IX. The reversal mechanism
      would be assumed to result from competition between DEA derivatives and
      chloroquine for efflux translocation sites, thus causing an increase in steady
      state accumulation of chloroquine and a return to susceptibility. Restoration of
      therapeutic efficacy of chloroquine against resistant parasites by the
      administration of an additional drug available at relatively low cost may be a
      more effective strategy than the introduction of another antimalarial drug at the
      national level.

PMID- 12224572
TI  - Molecular epidemiology of malaria in Cameroon. X. Evaluation of PFMDR1 mutations
      as genetic markers for resistance to amino alcohols and artemisinin derivatives.
AB  - Mutations at five positions in the Plasmodium falciparum multidrug-resistance
      gene 1 (pfmdr1), initially thought to confer resistance to chloroquine, have been
      associated with in vitro resistance to amino alcohols and artemisinin derivatives
      in more recent studies. To assess the possible association between drug
      resistance phenotype and pfmdrl polymorphisms and establish the baseline pfmdr1
      sequence data in Yaounde, Cameroon, the in vitro drug sensitivity pattern was
      determined for 64 clinical isolates by isotopic microtest. The pfmdr1 alleles
      were determined by a polymerase chain reaction and automatic sequencing. A large
      majority of isolates carried Tyr-86 (88%) and Phe-184 (91%) alleles. With the
      exception of one isolate with mixed codon 1246, all isolates had wild-type
      alleles Ser-1034, Asn-1042, and Asp-1246. There was no statistical association
      between codons 86 and 184 and in vitro response to chloroquine, amino alcohols,
      and artemisinin derivatives (P > 0.05). Our data do not seem to support the
      hypothesis that mutations in codons 86 and 184 influence the in vitro response to
      these drugs. Further monitoring of both in vitro response and pfmdrl
      polymorphisms is required to evaluate the potential role played by other pfmdr1
      alleles in the determination of drug resistance in Africa.

PMID- 12224573
TI  - Anemia in parasite- and recombinant protein-immunized aotus monkeys infected with
      Plasmodium falciparum.
AB  - Plasmodium falciparum-induced anemia was characterized in Aotus monkeys
      repeatedly immunized by infection with P. falciparum (FVO strain) parasites, then
      cross-challenged with CAMP strain, or in monkeys receiving blood stage challenges
      as part of malaria vaccine trials. In 4 studies, 25 (30.5%) of 82 monkeys had at
      least a 50% reduction in hematocrit; mean day of maximum parasitemia was 12.5,
      whereas the mean day of minimum hematocrit was 18.8 (P < 0.0009). Decreased
      hematocrit levels were not associated with reticulocytosis until parasite
      densities decreased significantly from peak levels. Direct antibody tests to
      detect IgG and C3d on the surface of erythrocytes were negative.
      Nonantibody/noncomplement-mediated lysis of uninfected erythrocytes seems to be
      the principal cause of the anemia, and it also seems that bone marrow suppression
      and lysis of infected erythrocytes contributed to the anemia. Partial immunity
      whether induced by repeated immunization with whole parasites or with vaccine
      seems important to the development of anemia.

PMID- 12224574
TI  - A cost comparison of two malaria control methods in Kyunggi Province, Republic of
      Korea, using remote sensing and geographic information systems.
AB  - A cost-comparison of two methods for the control of malaria in the Republic of
      Korea was performed. The cost of larviciding with methoprene granules was
      estimated at $93.48/hectare. The annual cost of providing chemoprophylaxis was
      estimated at $37.53/person. Remote sensing and geographic information systems
      were used to obtain estimates of the size of vector larval habitats around two
      U.S. Army camps, allowing an estimate of the cost of larviciding around each of
      the camps. This estimate was compared to the cost of providing chloroquine and
      primaquine chemoprophylaxis for the camp populations. Costs on each of the camps
      differed by the size of the larval habitats and the size of the at-risk
      population. These tools allow extrapolation of larval surveillance data to a
      regional scale while simultaneously providing site-specific cost analysis, thus
      reducing the cost and labor associated with vector surveillance over large areas.

PMID- 12224575
TI  - Prognostic value of thrombocytopenia in African children with falciparum malaria.
AB  - Thrombocytopenia is a common finding in malaria, but its prognostic value has not
      been addressed in children. The relationship between thrombocytopenia (platelet
      count < 100,000/mm3 on admission) and severity and outcome was investigated
      prospectively in children hospitalized with falciparum malaria in Dakar, Senegal,
      an area that is hypoendemic for malaria. Of 288 falciparum cases, 215 matched the
      2000 World Health Organization definition of severe malaria. Median platelet
      counts were lower (98,000/mm3 versus 139,000/mm3; P < 0.02) among severe cases
      than in mild cases, and in children who died than among those who recovered
      (68,500/mm3 versus 109,000/mm3; P < 0.002). In severe cases, children presenting
      with a platelet count < 100,000/mm3 were more likely to die (odds ratio [OR] =
      6.31, 95% confidence interval [CI] = 2.0-26.0). Moreover, multivariate analysis
      identified thrombocytopenia as an independent predictor of death (OR = 13.3, 95%
      CI = 3.2-55.1). Our data show an association between thrombocytopenia and either
      severity or prognosis in childhood falciparum malaria.

PMID- 12224576
TI  - Nonimmune IgM, but not IgG binds to the surface of Plasmodium falciparum-infected
      erythrocytes and correlates with rosetting and severe malaria.
AB  - Recent work suggests that IgG and IgM from nonimmune human serum (natural
      antibodies) bind to the surface of Plasmodium falciparum-infected erythrocytes
      and contribute to rosette formation by stabilizing the interaction between
      infected and uninfected erythrocytes. Here we show, in both laboratory clones and
      field isolates, that only IgM but not IgG is detected on the surface of infected
      cells. In field isolates, there was a strong positive correlation between IgM
      binding and rosette formation (Spearman's rank correlation coefficient p = 0.804,
      P < 0.001). Both rosette formation and IgM binding were associated with severe
      malaria, although statistical analysis indicates that rosette formation is the
      more strongly associated variable. Rosette formation, but not IgM binding, was
      also associated with malarial anemia. We conclude that IgM is the predominant
      class of natural antibodies binding to the surface of infected erythrocytes.
      However, we could not confirm previous suggestions that infected erythrocytes are
      coated with nonimmune IgG, which could lead to their interaction with host
      Fcgamma receptors.

PMID- 12224577
TI  - Genetic complexity of Plasmodium falciparum gametocytes isolated from the
      peripheral blood of treated Gambian children.
AB  - The genetic complexity of Plasmodium falciparum gametocytes isolated from Gambian
      children participating in a controlled trial of anti-malarial therapy was
      investigated. RNA and DNA were prepared from gametocyte-positive blood, which was
      also used in transmission experiments with Anopheles gambiae mosquitoes.
      Amplification by a reverse transcriptase-polymerase chain reaction (RT-PCR) of
      transcripts from the genes for the ring-infected erythrocyte surface antigen and
      the 16-kD antigen, which exhibit asexual and sexual stage-specific expression,
      was used to identify 30 post-treatment gametocyte isolates in which trophozoites
      persisted below the threshold of detection by microscopy. These included isolates
      from children who received sulfadoxine/pyrimethamine plus artesunate. Twenty-nine
      gametocyte-positive isolates that were free of subpatent trophozoites were
      examined further by PCR amplification of polymorphic genomic loci. We estimate
      that an average minimum of 2.3 genotypes occurred in these gametocyte-only
      isolates, and many of these were shown to be infective to mosquitoes. Thus,
      meiotic recombination between different genotypes is predicted to be a common
      event in this study area.

PMID- 12224579
TI  - Andes virus associated with hantavirus pulmonary syndrome in northern Argentina
      and determination of the precise site of infection.
AB  - Hantavirus pulmonary syndrome (HPS) has been documented in the Salta and Jujuy
      provinces of northern Argentina since 1991 and 1997, respectively, accounting for
      almost 50% of the cases of HPS reported in this country. Andes (AND) virus,
      specifically the AND virus Nort lineage, was previously associated with human
      disease in this region. Genetic analysis of viral medium RNA segments obtained
      from 18 HPS cases showed the existence of three AND virus Nort sublineages co
      circulating in these two provinces. They showed a nucleotide sequence diversity
      of up to 11.1% between the sublineages. The putative site of infection of one of
      these cases (Sal3/97) was determined. A 100% nucleotide sequence identity was
      observed between the viral sequence found in patient Sal3/97 and in two virus
      positive Oligoryzomys chacoensis captured in the same place where the case lived
      and worked. These results indicated the putative site of infection and identified
      this rodent species as the source of infection.

PMID- 12224578
TI  - Progressive Chagas' cardiomyopathy is associated with low selenium levels.
AB  - Selenium (Se) deficiency is linked with some cardiomyopathies. Its status was
      determined in 170 patients with chronic Chagas' disease from 2 Brazilian regions
      (Rio de Janeiro and Belo Horizonte), clinically stratified into groups as
      follows: indeterminate or asymptomatic (IND); cardiac asymptomatic (CARDa);
      cardiac symptomatic with moderate to severe heart dysfunction (CARDb); and
      healthy adults (HA), used for comparison. In most HA, Se levels were normal,
      excluding an overall Se deficiency. Se was significantly lower in CARDb than in
      HA, IND, or CARDa patients. This was not associated with a concomitant decrease
      in activity of glutathione peroxidase. Thyrotropin was normal, excluding iodine
      deficiency. Se correlated positive and significantly with ventricular ejection
      fraction (assessed via echocardiography). Asymptomatic children with acute
      Chagas' disease had normal Se as well as 5 noninfectious cases of cardiomyopathy.
      Low Se was found in 6 of 10 chagasic patients with digestive megasyndromes. Thus,
      the decrease in Se in chagasic patients seems to be a biological marker for
      Trypanosoma cruzi infection and related to the progression of pathology.

PMID- 12224580
TI  - Hepatitis e virus infection in fulminant hepatitis patients and an apparently
      healthy population in Bangladesh.
AB  - This is the first study comparing hepatitis E virus (HEV) infection in Bangladesh
      in fulminant hepatitis (FH) patients presumed to have a viral cause and in the
      apparently healthy population. Sera from 22 FH patients were analyzed for
      antibodies to hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C and D
      viruses, and HEV and for hepatitis B surface antigen (HBsAg). Anti-HEV
      immunoglobulin M (IgM) was detected in the sera of 63.6% of patients, whereas
      35.7% were positive for HBsAg. A high prevalence of HEV infection (83.3%) was
      noted in the HBV carriers. Serum samples from 273 apparently healthy individuals
      were tested for antibodies to HAV and HEV. Anti-HEV IgM was detected in 7.3% of
      the samples. The seroprevalence of HAV differed from that of HEV in the same
      population because all samples were negative for anti-HAV IgM. These data
      indicate that HEV infection is highly endemic in Bangladesh.

PMID- 12224581
TI  - Randomized comparison of low-dose versus standard-dose praziquantel therapy in
      treatment of urinary tract morbidity due to Schistosoma haema tobium infection.
AB  - At present, anthelmintic therapy with praziquantel at a dose of 40 mg/kg of body
      weight is the recommended treatment for control of urinary tract morbidity caused
      by Schistosoma haematobium. Although this standard regimen is effective, drug
      cost may represent a significant barrier to implementation of large-scale
      schistosomiasis control programs in developing areas. Previous comparison trials
      have established that low-dose (20-30 mg/kg) praziquantel regimens can
      effectively suppress the intensity of S. haematobium infection in endemic
      settings. However, the efficacy of these low-dose regimens in controlling
      infection-related morbidity has not been determined in a randomized field trial.
      The present random allocation study examined the relative efficacy of a 20 mg/kg
      dose versus a 40 mg/kg dose of praziquantel in control of hematuria and bladder
      and renal abnormalities associated with S. haematobium infection in an endemic
      area of Coast Province, Kenya. After a nine-month observation period, the results
      indicated an advantage to the standard 40 mg/kg praziquantel dose in terms of
      reduction of infection prevalence and hematuria after therapy (P < 0.01 and P <
      0.005, respectively). However, the two treatment groups were equally effective in
      reducing structural urinary tract morbidity detected on ultrasound examination.
      We conclude that in certain settings, a 20 mg/kg dose of praziquantel may be
      sufficient in providing control of morbidity due to urinary schistosomiasis in
      population-based treatment programs.

PMID- 12224582
TI  - Differentiation of entamoeba histolytica/entamoeba dispar by PCR and their
      correlation with humoral and cellular immunity in individuals with clinical
      variants of amoebiasis.
AB  - To correlate a particular state of immunity with Entamoeba spp., we used
      colorimetric PCR to differentiate E. histolytica from E. dispar in individuals
      with amoebiasis and to associate its presence with the clinical profile,
      including humoral and cellular immune responses to E. histolytica. Our results
      showed high levels of antibody in acute amoebiasis and elevation of IL-4
      production, a cytokine related to Th2 profile, associated with E. histolytica. In
      chronic amoebiasis, even with anti-E. histolytica seropositivity, intestinal
      symptoms were associated with E. dispar in all the cases, without differences in
      level of antibodies, BTI, CD4+/CD8+ ratio, INF-gamma, and IL-4. Among
      asymptomatic carriers, E. dispar was more frequently found; however,
      identification of E. histolytica in two asymptomatic carriers associated with
      high levels of INF-gamma, a cytokine related to Th1 profile, demonstrate the
      importance of making specific diagnosis of Entamoeba spp., to establish the
      clinical and epidemiological behavior in both intestinal and extra-intestinal
      amoebiasis.

PMID- 12224583
TI  - Heterogeneity, geographic distribution, and pathogenicity of serodemes of
      Leishmania viannia in Colombia.
AB  - Leishmania Viannia strains from 1,092 patients who acquired dermal leishmaniasis
      in endemic regions of Colombia were analyzed for expression of species and
      subgenus specific epitopes. Eight monoclonal antibodies prepared against
      membranes of the major species of the Viannia subgenus and previously shown to
      distinguish these species, recognized low molecular mass (< 45kD) membrane
      components. Thirteen widely but non-uniformly distributed serodemes were
      identified: one unique to L. panamensis, four unique to L. braziliensis and eight
      that were common to L. braziliensis and L. guyanensis. Thirty-seven percent of
      Colombian L. braziliensis strains concomitantly typed by isoenzymes were null,
      i.e., not recognized by the corresponding species-specific B-16 or B-18
      antibodies. No Colombian L. guyanensis strains were recognized by the antibody
      specific for this species (B-19). In contrast, L. panamensis-specific B-4 and B11
      antibodies recognized > 98% of the L. panamensis strains. Null strains of L.
      braziliensis and L. panamensis were more frequently isolated from mucosal
      leishmaniasis than strains that expressed species specific epitopes, suggesting
      that these strains may be more pathogenic.

PMID- 12224584
TI  - Evaluation of two enzyme-linked immunosorbent assay methods for detection of
      immunoglobulin M antibodies in acute leptospirosis.
AB  - Leptospirosis is a common zoonosis of worldwide distribution. Diagnosis of
      leptospirosis is usually accomplished by serology, but the microscopic
      agglutination test (MAT) generally requires paired sera for detection of
      seroconversion and is considered too complex for routine use. A number of rapid
      assays have been developed in recent years. In the present study, 2
      immunoglobulin (Ig) M enzyme-linked immunosorbent assay (ELISA) methods were
      evaluated for the early diagnosis of acute leptospirosis in Barbados. A total of
      103 patients admitted to the Queen Elizabeth Hospital for diagnosis of suspected
      leptospirosis were investigated. A case of leptospirosis was confirmed by a 4
      fold rise in titer between 2 sera tested by MAT, an initial titer of > or = 800
      in the MAT, or by isolation of leptospires from blood or urine. A total of 48
      cases of leptospirosis were confirmed. In 33 cases, both commercial assays were
      positive in the first sample, taken at admission, a mean of 6.7 days after onset
      of symptoms, whereas seroconversion was detected in a further 9 cases. Both
      assays were negative in 5 cases, and the remaining case gave discordant results
      in the 2 assays. False-positive IgM results were detected in 4 patients without
      leptospirosis. The sensitivity of the 2 assays was 89.6 and 97.5%, respectively,
      and specificities were 92.7 and 96.4%, respectively. The positive predictive
      values were 87.8 and 95.5%, and the negative predictive values were 90.7 and
      89.5%, respectively. Either of these assays can be used for early diagnosis of
      leptospirosis, particularly in laboratories that cannot perform more specialized
      leptospiral serology.

PMID- 12224585
TI  - Serology and eosinophil count in the diagnosis and management of strongyloidiasis
      in a non-endemic area.
AB  - Strongyloidiasis is a chronic infection that may result in significant morbidity;
      however, diagnosis and management remain problematic. The objective of this study
      was to 1) evaluate the demographic, clinical, and laboratory features of 76
      consecutive individuals who had Strongyloides stercoralis larvae identified in
      their fecal specimens; 2) determine the sensitivity of the Centers for Disease
      Control and Prevention (CDC) enzyme immunoassay (EIA) for detecting antibodies to
      Strongyloides in those with confirmed infection; and 3) assess the serologic
      responses and changes in eosinophil counts following treatment. Most (96%) cases
      occurred in immigrants, but some patients had immigrated as long as 40 years
      earlier. The CDC Strongyloides EIA had a sensitivity of 94.6% (95% confidence
      interval = 92.0-97.2%) in this patient population with proven infection.
      Serologic and eosinophil counts decreased after therapy, suggesting that they may
      be useful markers of treatment success.

PMID- 12224586
TI  - The epidemiology of tick-borne relapsing fever in the United States.
AB  - Each year, many residents of and visitors to endemic regions of the western
      United States are exposed to the vector of tick-borne relapsing fever (TBRF), an
      underrecognized and underreported disease. Through review of report forms and
      literature review, we identified 450 cases of TBRF acquired in the United States
      in 11 western states (and in British Columbia by a U.S. resident) from January
      1977 to January 2000. Exposure sites were in forested areas, at varying
      elevations, in mountainous regions (Cascade, Rocky Mountain, San Bernardino, and
      Sierra Nevada ranges) of the United States and Canada and in limestone caves in
      central Texas. Only 13 counties accounted for approximately 50% of all cases.
      Forty percent of the cases were not residents of the state where TBRF exposure
      occurred, including 7% from 11 states where TBRF is not endemic. TBRF is endemic
      in the United States and is a disease affecting travelers, who may return home
      with the disease to areas where physicians are not familiar with it.

PMID- 12224587
TI  - Short report: a rapid method for the differentiation of Burkholderia pseudomallei
      and Burkholderia thailandensis.
AB  - A rapid method for the identification and differentiation of Burkholderia
      pseudomallei and Burkholderia thailandensis colonies is described. It consists of
      simultaneous use of 2 monoclonal antibody-based latex agglutination test systems.
      The anti-lipopolysaccharide test reacts with both species, whereas the anti
      exopolysaccharide reacts only with B. pseudomallei. Compared with classical
      biochemical tests, the method is highly reproducible and accurate. It is
      particularly useful for the identification of the organisms in environmental
      specimens, which may contain both of these Burkholderia species.

PMID- 12224588
TI  - Short report: increased level of serum nitric oxide in patients with dengue.
AB  - Nitric oxide (NO) has been involved in several infectious diseases. Virus dengue
      is capable of inducing increased levels of NO when cocultured with human Kupffer
      and spleen cells. However, no reports describe the levels of NO in patients with
      dengue infection. Increased levels of NO were found in patients with the classic
      form of the disease; however, in the hemorrhagic form of the disease, similar
      levels to those of healthy controls were found. In vitro studies showed no
      increased levels of NO when human platelets were incubated with the virus.
      Increased NO in classical dengue could be important in the evolution from the
      nonhemorrhagic to the hemorrhagic forms of dengue.

PMID- 12224589
TI  - Epidemiology of dengue in Sri Lanka before and after the emergence of epidemic
      dengue hemorrhagic fever.
AB  - Before 1989, dengue epidemiology in Sri Lanka was characterized by frequent
      transmission of all four dengue serotypes but a low incidence of dengue
      hemorrhagic fever (DHF). After 1989, cases of DHF dramatically increased. Here we
      present the results of epidemiologic studies conducted in Colombo, Sri Lanka
      before and after epidemic emergence of DHF in 1989. We compared the proportion of
      dengue cases among people with fever attending clinics from 1980 to 1984 and in
      1997 and 1998 to determine if an increase in dengue transmission was associated
      with more DHF cases being reported. We also compared the relative distribution of
      dengue virus serotypes circulating in Colombo before and after the emergence of
      DHF. We detected no significant differences in dengue as a proportion of fever
      cases or in serotype distribution between the pre and post-DHF periods. We
      conclude that an increase in virus transmission or a change in circulating
      serotypes does not explain the epidemic emergence of DHF in Sri Lanka.

PMID- 12224590
TI  - Hypereosinophilia and liver mass in an immigrant.
AB  - Human infection with the sheep liver fluke Fasciola hepatica is a global zoonosis
      that usually parallels the prevalence of infection in sheep and other ruminants.
      The disease is endemic in South and Central America, Puerto Rico, the Caribbean
      region, many parts of Africa, Asia, the Middle East, Australia, and China. There
      have been a number of focal outbreaks reported from Europe, including southern
      France and the Mediterranean region. Since acute fascioliasis has rarely been
      reported in the United States, physicians in this country frequently overlook the
      diagnosis. Therefore, we report a case of acute human fascioliasis and review the
      pathogenesis, diagnosis, and treatment of this disease in a recently arrived
      immigrant.

PMID- 12224591
TI  - Discrimination between active and inactive neurocysticercosis by metacestode
      excretory/secretory antigens of Taenia solium in an enzyme-linked immunosorbent
      assay.
AB  - To detect IgG antibodies to Taenia solium, a controlled double-blind study was
      conducted using 91 coded cerebrospinal fluid samples from patients with
      neurocysticercosis (NCC) and other neurologic disorders. Samples were tested in
      an enzyme-linked immunosorbent assay (ELISA) using metacestode
      excretion/secretion antigens. The results were correlated with data from medical
      records on the diagnosis of NCC (based on computed tomography and magnetic
      resonance imaging criteria) and other neurologic disorders. The ELISA results
      were positive in 22 of the 24 cases with active NCC. In contrast, six cases with
      calcified cysts (inactive NCC), as well as one case in a transitional stage, were
      negative. One case with a calcified granuloma and another with a granuloma plus
      calcifications (classified as inactive NCC) had positive results. The remaining
      negative results corresponded to other neurologic disorders (58 cases). The
      results of the ELISA showed a significant difference between active and inactive
      NCC (P = 0.0034).

PMID- 12224592
TI  - Survival and growth of Shigella flexneri, Salmonella enterica serovar
      enteritidis, and Vibrio cholerae O1 in reconstituted infant formula.
AB  - Formula feeding is an alternative method to prevent mother-to-child infection
      with human immunodeficiency virus through breast-feeding in developing countries.
      Growth of bacterial pathogens in reconstituted infant formula has become a health
      hazard when contaminated water is used for rehydration. This study was conducted
      to assess bacterial safety risk of using contaminated water to reconstitute
      infant formula. Survival and growth characteristics were determined for three
      bacterial pathogens, Vibrio cholerae O1, Shigella flexneri, and Salmonella
      enterica serovar Enteritidis, inoculated into sterile tap water (3.2-3.4 log10
      colony-forming units [CFU]/ml) and infant formula (1.5-1.7 and 3.2-3.4 log10
      CFU/ml) and incubated at 4 degrees C or 30 degrees C for up to 24 hours. Vibrio
      cholerae O1 was the most sensitive of the three pathogens when inoculated into
      water, with no viable cells detected within 2 hours at 4 degrees C or 30 degrees
      C. The rate of inactivation in water was greater at 30 degrees C than at 4
      degrees C. Vibrio cholerae O1, Shigella flexneri, and Salmonella enterica serovar
      Enteritidis grew rapidly in infant formula at 30 degrees C, reaching populations
      of 9.2, 8.7, and 9.2 log10 CFU/ml, respectively, at 24 hours. Populations of all
      three pathogens did not change significantly after incubating infant formula for
      24 hours at 4 degrees C, but continuously decreased in water throughout
      incubation for 24 hours, regardless of temperature. Results suggest that unless
      refrigerated, reconstituted infant formula should be consumed soon after
      preparation to avoid increased risk of illness associated with increases in
      populations of pathogenic bacteria that may be introduced by contaminated water.

PMID- 12224593
TI  - Intra-familial and extra-familial risk factors associated with Cryptosporidium
      parvum infection among children hospitalized for diarrhea in Goiania, Goias,
      Brazil.
AB  - A cross-sectional study was conducted for assessing the prevalence of and risk
      factors associated with Cryptosporidium parvum in diarrheic children who were
      hospitalized in Goiania, capital of Goias State in Brazil. A crude prevalence of
      14.4% (64 of 445) was observed using a direct immunfluorescent assay (DFA), but
      the true prevalence was 18.7% (83 of 445) when a gold standard of immunomagnetic
      separation was used in combination with the DFA. Infection was more predominant
      in children less than 24 months old (odds ratio [OR] = 0.50, 90% confidence
      interval [CI] = 0.36-0.68, P = 0.0001), and males were 2.2 times more at risk for
      infection when compared with females (OR = 2.2. 90% CI = 0.13-3.8, P = 0.01). The
      socioeconomic, intra-familial, and environmental factors associated with
      cryptosporidiosis were day care attendance, household children with diarrhea up
      to 30 days prior to the interview, contact with surface water within past 30 days
      prior to the interview, dwelling distance from a body of water, and the late
      rainy season (P < 0.10). C. parvum was not associated with the parent's
      occupation, household sleeping arrangements, number of caregivers, breast-fed
      children, diet and type of food hygiene, source and type of treatment of drinking
      water, presence of sewage, and animal exposure (P > 0.10). Although weight was
      not found to be associated with infection, children infected with C parvum
      weighed on average 2.0% less than children not infected with C. parvum (P >
      0.10). Thus, C. parvum is an important etiologic agent of childhood diarrhea and
      should be identified in routine parasitologic tests of diarrheal stool samples.

PMID- 12224594
TI  - Hyperendemic Cryptosporidium and Giardia in households lacking municipal sewer
      and water on the United States-Mexico border.
AB  - This study identified differences in the epidemiology of Giardia and
      Cryptosporidium infection for low-income populations residing on the United
      States-Mexico border. Participation included 77 households in three communities
      lacking adequate municipal water and sewage services. The household was the unit
      of analysis and sampling was from household biosolid waste from newly installed
      composting toilets. The proportion of households positive for Giardia and
      Cryptosporidium was high, 82% and 70%, respectively, and this was in contrast to
      the few households (14%) reporting at least one individual with diarrhea
      symptoms. This finding indicated that most of the participant families were
      chronically infected but asymptomatic. In the multivariate analysis, there was a
      statistically significant protective effect for Cryptosporidium in those
      households that purified drinking water but not for Giardia. Those households
      with children less than five years of age were 1.3 times at risk for Giardia
      infection. Our findings highlighted differences in the transmission mode of these
      two pathogens and underscore the need for interventions addressing hygiene, water
      supply, and sanitation.

PMID- 12224595
TI  - Seasonal prevalence of intestinal parasites in the United States during 2000.
AB  - One-third of 5,792 fecal specimens from 2,896 patients in 48 states and the
      District of Columbia tested positive for intestinal parasites during the year
      2000. Multiple infections with 2-4 parasitic species constituted 10% of 916
      infected cases. Blastocystis hominis infected 662 patients (23% or 72% of the 916
      cases). Its prevalence appears to be increasing in recent years. Eighteen other
      species of intestinal parasites were identified. Cryptosporidium parvum and
      Entamoeba histolytica/E. dispar ranked second and third in prevalence,
      respectively. Prevalence of infection was lowest (22-27%) in winter, gradually
      increased during the spring, reached peaks of 36-43% between July and October,
      and gradually decreased to 32% in December. A new superior method of parasite
      detection using the Proto-fix-CONSED system for fixing, transport, and processing
      of fecal specimens is described. In single infections, pathogenic protozoa caused
      asymptomatic subclinical infections in 0-31 % of the cases and non-pathogenic
      protozoa unexpectedly caused symptoms in 73-100% of the cases. The relationship
      between Charcot-Leyden crystals and infection with four species of intestinal
      parasites is examined and the list of provoking parasitic causes is expanded.

PMID- 12224596
TI  - A cocktail polymerase chain reaction assay to identify members of the Anopheles
      funestus (Diptera: Culicidae) group.
AB  - Anopheles funestus Giles is a major malaria vector in Africa belonging to a group
      of species with morphologically similar characteristics. Morphological
      identification of members of the A. funestus group is difficult because of
      overlap of distinguishing characteristics in adult or immature stages as well as
      the necessity to rear isofemale lines to examine larval and egg characters. A
      rapid rDNA polymerase chain reaction (PCR) method has been developed to
      accurately identify five members of the A. funestus group. This PCR is based on
      species-specific primers in the ITS2 region on the rDNA to identify A. funestus
      (approximately 505bp), Anopheles vaneedeni Gillies and Coetzee (approximately
      587bp), Anopheles rivulorum Leeson (approximately 411bp), Anopheles leesoni Evans
      (approximately 146bp), and Anopheles parensis Gillies (approximately 252bp).

PMID- 12224598
TI  - Absorption and metabolism of polyphenols in the gut and impact on health.
AB  - Polyphenols are the most abundant antioxidants in the human diet. They show a
      considerable structural diversity, which largely influences their
      bioavailability. Phenolic acids like caffeic acid are easily absorbed through the
      gut barrier, whereas large molecular weight polyphenols such as proanthocyanidins
      are very poorly absorbed. Once absorbed, polyphenols are conjugated to
      glucuronide, sulphate and methyl groups in the gut mucosa and inner tissues. Non
      conjugated polyphenols are virtually absent in plasma. Such reactions facilitate
      their excretion and limit their potential toxicity. The polyphenols reaching the
      colon are extensively metabolised by the microflora into a wide array of low
      molecular weight phenolic acids. The biological properties of both conjugated
      derivatives and microbial metabolites have rarely been examined. Their study will
      be essential to better assess the health effects of dietary polyphenols.
      Alternatively, some health effects of polyphenols may not require their
      absorption through the gut barrier. Their role as iron chelators in the gut lumen
      is briefly discussed.

PMID- 12224597
TI  - Baicalein inhibits DMBA-DNA adduct formation by modulating CYP1A1 and CYP1B1
      activities.
AB  - Flavonoids are phenolic compounds isolated from plants, and several of them like
      genistein and quercetin, have been documented to be effective in preventing
      cancer. Baicalein, a flavonoid extracted from the root of Scutellaria species, is
      widely used as a health supplement and herbal medicine in Asian countries. In
      this study, the chemopreventive effect of baicalein on 7,12
      dimethylbenz[a]anthracene (DMBA)-induced DNA damage was evaluated in an
      established cell culture model. In a preliminary screening, baicalein was
      identified to be a strong inhibitor to EROD activities induced by DMBA in MCF-7
      cells. Subsequent enzyme kinetic analysis revealed that baicalein was a
      competitive inhibitor to EROD, and CYP1A1 and CYP1B1 gene expressions were also
      determined. Baicalein could reduce the CYP1A1/1B1 mRNA expressions induced by
      DMBA, and the mRNA abundance of CYP1A1 appeared to be more responsive than that
      of CYP1B1. A XRE-luciferase gene reporter assay indicated that AhR
      transactivation was suppressed. Since CYP1A1/1B1 were responsible for the
      biotransformation of polycyclic aromatic hydrocarbons, baicalein also
      demonstrated its ability to reduce DMBA-DNA adduct formation in MCF-7 cells. This
      study suggested that the natural occurring baicalein could be an agent preventing
      carcinogen-DNA adduct formation.

PMID- 12224599
TI  - Randomized, controlled trial of phytoestrogen in the prophylactic treatment of
      menstrual migraine.
AB  - Approximately 30% of women afflicted with migraine have menstrually associated
      attacks. These migraines are often refractory to treatment. Evidence suggests
      estrogen and progestin fluctuations may influence menstrual migraine.
      Phytoestrogens have demonstrated estrogenic effects in some tissues, but are
      without stimulation of the endometrium, suggesting decreased risk with long-term
      use. This study was undertaken to assess the efficacy of a phytoestrogen
      combination in the prophylactic treatment of menstrual migraine. Forty-nine
      patients were randomized to receive either placebo, or a daily combination of 60
      mg soy isoflavones, 100 mg dong quai, and 50 mg black cohosh, with each component
      standardized to its primary alkaloid. Patients received study medication for 24
      weeks. Average frequency of menstrually associated migraine attacks during weeks
      9-24 was reduced from 10.3 +/- 2.4 (mean +/- s.e.m.) in placebo treated patients
      to 4.7 +/- 1.8 (P < 0.01) in patients treated with the phytoestrogen preparation.

PMID- 12224600
TI  - Difference in flavonoid and isoflavone profile between soybean and soy leaf.
AB  - The present study was to compare the flavonoid profile between soybean and soy
      leaves. Soybean was most abundant in malonyl-genistin followed by malonyl
      daidzin, genistin, daidzin, genistein and daidzein in a decreasing order. In
      contrast, soy leaves contained only trace amounts of malonyl-genistin and
      genistin, but they had the six unknown flavonoids that were absent in soybean.
      The six unknown compounds were isolated by using various chromatographic
      techniques and the structures were identified by studying their varying spectra
      of ultraviolet (UV), infrared (IR), Mass, 1H-NMR and 13C-NMR. It was found that
      the six unknown compounds were all kaempferol glycosides namely kaempferol-3-O
      alpha-L-rhamnopyranosyl (1-->2)-beta-D-glucopyranosyl (1-->6)-beta-D
      galactopyranoside, kaempferol-3-O-(2,6-di-O-alpha-rhamnopyranosyl)-beta
      galactopyranoside, kaempferol-3-O-alpha-L-rhamnopyranosyl (1-->6)-beta-D
      galactopyranoside, kaempferol-3-O-digalactopyranoside, kaempferol-3-O
      diglucopyranoside and kaempferol-3-O-rutinoside. It was concluded that the
      flavonoids in soy leaves were mainly kaempferol glycosides, whereas those in
      soybean were mainly isoflavone glycosides and derivatives.

PMID- 12224601
TI  - Cancer preventive effects of flavonoids--a review.
AB  - A cancer protective effect from plant-derived foods has been found with uncommon
      consistency in epidemiologic studies. However, it has been difficult to identify
      specific components responsible for this effect. Many phytochemicals have been
      shown to be biologically active and they may interact to protect against cancer.
      In recent years, experimental studies have provided growing evidence for the
      beneficial action of flavonoids on multiple cancer-related biological pathways
      (carcinogen bioactivation, cell-signaling, cell cycle regulation, angiogenesis,
      oxidative stress, inflammation). Although the epidemiologic data on flavonoids
      and cancer are still limited and conflicting, some protective associations have
      been suggested for flavonoid-rich foods (soy and premenopausal breast cancer;
      green tea and stomach cancer; onion and lung cancer). This review focuses on the
      biological effects of the main flavonoids, as well as the epidemiologic evidence
      that support their potential cancer protective properties.

PMID- 12224602
TI  - Isoflavones for prevention of cancer, cardiovascular diseases, gynecological
      problems and possible immune potentiation.
AB  - Japanese women show low incidence of and mortality from breast cancer,
      cardiovascular disease and climacteric symptoms compared to Caucasians. High soy
      bean intake is considered to attribute to that, but it is not clear whether soy
      protein itself or isoflavones (IFs) mixed in the soy protein has such effects.
      Presence of IFs in soy beans was varied by site, so we made IF-rich tablets from
      daidzein-rich soy germ (hypocotyl) for intervention studies. Our intervention
      study on young women by using the IF-rich tablet (20 and 40 mg/day) showed slight
      elongation of the menstrual cycle, but no adverse effects occurred. Intervention
      study on climacteric women showed improvement of bone density, hypertension and
      climacteric symptoms. Health effects of IFs on cancer occurrence, cardiovascular
      diseases, gynecological problems and possible immune potentiation are reviewed
      from functional aspects.

PMID- 12224603
TI  - A life course approach to veterinary science.

PMID- 12224605
TI  - Making the case for zoning.

PMID- 12224604
TI  - Keeping out of trouble: what you need to know about Withholding Periods.

PMID- 12224606
TI  - Testing Australia's preparedness for FMD.

PMID- 12224607
TI  - Re: the diffculty in enticing veterinarians into rural practice.

PMID- 12224608
TI  - Report on the number and distribution of vets.

PMID- 12224609
TI  - The main growth area in rural practice has been in the servicing of hobby farmers
      on the outskirts of cities and provincial towns.

PMID- 12224610
TI  - Are we as a profession becoming ruder and more ill-mannered amongst ourselves?

PMID- 12224612
TI  - The RSPCA of Papua New Guinea is in trouble.

PMID- 12224611
TI  - It is not always easy to find other practitioners with whom one can have an open
      and frank discussion.

PMID- 12224613
TI  - Regarding the international standing and quality of the AVJ.

PMID- 12224614
TI  - Longitudinal study of veterinarians from entry to the veterinary course to ten
      years after graduation: career paths.
AB  - OBJECTIVE: To map out the career paths of veterinarians during their first 10
      years after graduation, and to determine if this could have been predicted at
      entry to the veterinary course. DESIGN: Longitudinal study of students who
      started their course at The University of Queensland in 1985 and 1986, and who
      completed questionnaires in their first and fifth year as students, and in their
      second, sixth and eleventh year as veterinarians. METHODS: Data from 129 (96%)
      questionnaires completed during the eleventh year after graduation were coded
      numerically then analysed, together with data from previous questionnaires, with
      SAS System 7 for Windows 95. RESULTS: Ten years after they graduated, 80% were
      doing veterinary work, 60% were in private practice, 40% in small animal practice
      and 18% in mixed practice. The equivalent of 25% of the working time of all
      females was taken up by family duties. When part-time work was taken into
      account, veterinary work constituted the equivalent of 66% of the group working
      full-time. That 66% consisted of 52% on small animals, 7% on horses, 6% on
      cattle/sheep and 1% on pigs/poultry. Those who had grown up on farms with animals
      were twice as likely to be working with farm animals as were those from other
      backgrounds. Forecasts made on entry to the veterinary course were of no value in
      predicting who would remain in mixed practice. CONCLUSIONS: Fewer than one-fifth
      of graduates were in mixed practice after 10 years, but the number was higher for
      those who grew up on farms with animals. Forecasts that may be made at interview
      before entry to the course were of little value in predicting the likelihood of
      remaining in mixed veterinary practice.

PMID- 12224615
TI  - Longitudinal study of veterinarians from entry to the veterinary course to 10
      years after graduation: attitudes to work, career and profession.
AB  - OBJECTIVE: To describe the attitudes of veterinarians to their work, career and
      profession during the 10 years after graduation. DESIGN: Longitudinal study of
      students who started their course at The University of Queensland in 1985 and
      1986, and who completed questionnaires in their first and fifth year as students,
      and after one, five and 10 years as veterinarians. METHODS: Data from 129 (96%)
      questionnaires completed after 10 years as a veterinarian were coded numerically
      then analysed, together with data from previous questionnaires, with SAS System 7
      for Windows 95. RESULTS: After 10 years, almost all respondents were either very
      glad they had done the veterinary course (57%) or generally glad, though with
      some misgivings (37%). Despite this, only 55% would definitely become a
      veterinarian if they 'had to do it over again'. The responses for about one-third
      were different from those given five years earlier. The views of many were
      related to the level of support and encouragement received in their first job
      after graduation. There were 42% who were working less than half-time as
      veterinarians, and their main reasons were, in order, raising children, long
      hours of work, attitudes of bosses and clients, and poor pay. A majority was
      concerned about the ethics and competence of some colleagues, and almost all
      believed that consideration of costs must influence the type of treatment animals
      receive. CONCLUSIONS: Most veterinarians were glad to have done the veterinary
      course, but for about one-quarter their career had not lived up to expectations
      and almost half would not do it again in another incarnation. Stress, hours of
      work, difficulties in balancing personal life with career and low income were
      important concerns for many. Low income may contribute to the low number of males
      entering the veterinary profession.

PMID- 12224616
TI  - Treatment of an acromegalic cat with the dopamine agonist L-deprenyl.
AB  - Acromegaly was diagnosed in a 14-year-old domestic short hair cat presented for
      investigation and management of apparently insulin-resistant diabetes mellitus.
      Treatment with L-deprenyl and high doses of insulin was commenced. The L-deprenyl
      did not reduce the requirement for high doses of insulin and did not appear to
      reduce the clinical signs associated with the disease. The cat was euthanased one
      year after initial presentation.

PMID- 12224617
TI  - Prions in skeletal muscle.

PMID- 12224618
TI  - Synchronisation of oestrus and reproductive performance of dairy cows following
      administration of oestradiol benzoate or gonadotrophin releasing hormone during a
      synchronised pro-oestrus.
AB  - OBJECTIVE: To compare the use of gonadotrophin releasing hormone (GnRH) and
      oestradiol benzoate (ODB) administered following a synchronised pro-oestrus on
      reproductive performance of lactating dairy cows and the submission rates of non
      pregnant cows following resynchronisation. DESIGN: Cohort study. PROCEDURE:
      Lactating Holstein cows enrolled in a controlled breeding program were first
      treated with an intravaginal progesterone releasing insert (IVP4) for 8 days, 2.0
      mg of ODB intramuscular (i.m.) at device insertion (Day 0), an analogue of
      PGF2alpha at device removal and either 1.0 mg of ODB i.m., 24 h after device
      removal (ODB group, n = 242), or 0.25 mg of a GnRH agonist (GnRH group, n = 152)
      injected i.m. approximately 34 h after device removal. Every cow was artificially
      inseminated between 49 and 56 h after removal of its insert (Day 10). Cows
      detected in oestrus 1 day after artificial insemination (AI) that were not
      detected in oestrus on the previous day were re-inseminated on that day. All cows
      treated on Day 0 were resynchronised for reinsemination by insertion of a used
      IVP4 device on Day 23. Oestradiol benzoate at a dose of 1.0 mg was administered
      i.m. at the time of device insertion. Inserts were removed 8 days later (Day 31)
      and 1.0 mg of ODB was injected i.m. 24 h later. Those cows detected in oestrus
      between Days 31 and 35 were artificially inseminated. On Day 46 these cows were
      resynchronised for a third round of AI by insertion of an IVP4 device, used
      previously to synchronise cows for the first and second rounds of AI, and
      administration of 1.0 mg of ODB i.m.. Eight days later inserts were removed. Cows
      detected in oestrus between Days 54 and 58 were artificially inseminated. Bulls
      were run with the herd between rounds of AI and removed after 21 weeks of mating.
      RESULTS: Treatment with ODB or GnRH at the first synchronised pro-oestrus did not
      significantly alter the reproductive performance over three rounds of AI or over
      a 21-week breeding period. Treatment also did not alter submission rates at the
      second round of AI or the proportion of non-pregnant and non-return cows
      ('phantom' cows) detected and did not result in significant differences in
      concentrations of progesterone in plasma 10 and 18 days after removal of inserts
      at the first round of AI. Treatment with GnRH reduced the proportion of cows
      detected in oestrus at the first round of AI (36.2 vs 97.5%; P < 0.001).
      CONCLUSION: Administration of GnRH compared to ODB at a synchronised pro-oestrus
      results in similar reproductive performance. Treatment with GnRH reduced the
      proportion of cows detected in oestrus following treatment. This may offer
      advantages to the way AI is managed by enabling insemination at a fixed-time and
      removing the need for the detection of oestrus.

PMID- 12224619
TI  - Effect of the interval between shearing and dipping on the spread of
      Corynebacterium pseudotuberculosis infection in sheep.
AB  - OBJECTIVE: To determine whether the spread of Corynebacterium pseudotuberculosis
      infection to sheep in dips could be controlled by increasing the time between
      shearing and dipping. DESIGN: A controlled treatment trial where only the time
      between shearing and dipping was varied. ANIMALS AND PROCEDURE: One hundred and
      ninety-five sheep were found to be negative for C. pseudotuberculosis exposure by
      assay of CLA toxin antibody, were divided into four treatment groups. Each was
      shorn at either 0, 2, 4 or 8 weeks before dipping in a solution containing C.
      pseudotuberculosis. Blood samples were taken 6 weeks after dipping and sheep were
      slaughtered 12 weeks after dipping. A fifth smaller group of 14 sheep shorn 26
      weeks before dipping, was also exposed to C. pseudotuberculosis and was
      slaughtered with the other sheep. RESULTS: The occurrence of caseous
      lymphadenitis abscesses did not differ between groups or with sheep shorn 26
      weeks before dipping. The proportion of sheep that seroconverted to the C.
      pseudotuberculosis toxin and cell wall ELISA was larger in sheep dipped
      immediately after shearing than in sheep in the other groups. CONCLUSIONS:
      Delaying dipping until 8 weeks after shearing did not decrease the C.
      pseudotuberculosis infection rate due to dipping. Sheep dipped immediately after
      shearing developed higher concentrations of antibody to C. pseudotuberculosis
      than sheep when dipping occurred between 2 and 8 weeks and later after shearing.

PMID- 12224621
TI  - Confirmation of the prevention of vertical transmission of Neospora caninum in
      cattle by the use of embryo transfer.

PMID- 12224620
TI  - Concurrent spirochaetal infections of the feet and colon of cattle in Japan.
AB  - OBJECTIVE: To describe spirochaetal infections in the feet and colon of cattle
      affected with papillomatous digital dermatitis (PDD) and colitis respectively.
      PROCEDURE: Eighty-two slaughtered animals were macroscopically examined for the
      presence of PDD. Tissues of two cattle affected with PDD were examined by
      histology, immunohistochemistry, electron microscopy and bacteriology for
      spirochaetal infection. RESULTS: Two adult cattle (a 2-year-old beef bullock and
      7-year-old Holstein dairy cow) were affected with PDD. Histologically, numerous
      argyrophilic and gram-negative filamentous or spiral spirochaetes were found deep
      in the PDD lesions. Epithelial and goblet cell hyperplasia and oedema of the
      lamina propria mucosa with macrophage and lymphocyte infiltration were observed
      in the caecum and colon in the cattle. Numerous spirochaetes were present in the
      crypts and some had invaded epithelial and goblet cells, and caused their
      degeneration. Immunohistochemically the organisms stained positively with
      polyclonal antisera against Treponema pallidum and Brachyspira (Serpulina)
      hyodysenteriae. Ultrastructurally, the intestinal spirochaetes were similar to
      the spirochaetes in PDD. They were 6 to 14 pm long, 0.2 to 0.3 pm wide and had 4
      to 6 coils and 9 axial filaments per cell. Campylobacter species were isolated
      from the PDD and intestinal lesions, but spirochaetes were not. CONCLUSION:
      Concurrent infections with morphologically similar spirochaetal organisms may
      occur in the feet and colon of cattle in Japan.

PMID- 12224622
TI  - Genetic testing for progressive retinal atrophy in Irish Setters, an update.

PMID- 12224624
TI  - Eradication of feral pigs from Australia.

PMID- 12224623
TI  - Eradication of feral pigs from Australia.

PMID- 12224625
TI  - Growth-promoting activity of pyrazinoic acid, a putative active compound of
      antituberculosis drug pyrazinamide, in niacin-deficient rats through the
      inhibition of ACMSD activity.
AB  - We have recently reported that the antituberculosis drug, pyrazinamide (PZA),
      caused a significant increase in the conversion ratio of tryptophan to niacin in
      rats. In the present work, we investigated whether or not pyrazinoic acid (POA),
      a putative metabolite of PZA, increased the conversion ratio of tryptophan to
      niacin. Weaning rats were fed with a niacin-free and tryptophan-limited diet
      (negative control diet), or with the negative control diet supplemented with
      0.003% nicotinic acid (positive control diet) or 1% POA (test diet) for 27 days.
      The growth rate was almost same between the groups fed on the positive control
      diet and the test diet. Dietary POA significantly increased the conversion ratio
      of tryptophan to niacin. Although POA did not directly inhibit the activity of
      alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD), the
      rate-limiting enzyme in the tryptophan-niacin pathway, liver ACMSD activity was
      only not detected in the test diet group. These results suggest that a derivative
      of POA metabolized by rats inhibited the ACMSD activity.

PMID- 12224626
TI  - Thermal inactivation and product inhibition of Aspergillus terreus CECT 2663
      alpha-L-rhamnosidase and their role on hydrolysis of naringin solutions.
AB  - The kinetics of thermal inactivation of A. terreus alpha-rhamnosidase was studied
      using the substrate p-nitrophenyl alpha-L-rhamnoside between 50 degrees C and 70
      degrees C. Up to 60 degrees C the inactivation of the purified enzyme was
      completely reversible, but samples of crude or partially purified enzyme showed
      partial reversibility. The presence of the product rhamnose, the substrate
      naringin, and other additives reduced the reversible inactivation, maintaining in
      some cases full enzyme activity at 60 degrees C. A mechanism for the inactivation
      process, which permitted the reproduction of experimental results, was proposed.
      The products rhamnose (inhibition constant, 2.1 mM) and prunin (2.6 mM)
      competitively inhibited the enzyme reaction. The maximum hydrolysis of
      supersaturated naringin solution, without enzyme inactivation, was observed at 60
      degrees C. Hydrolysis of naringin reached 99% with 1% naringin solution, although
      the hydrolysis degree of naringin was only 40% due to products inhibition when
      the initial concentration of flavonoid was 10%. The experimental results fitted
      an equation based on the integrated Michaelis-Menten's, including competitive
      inhibition by products satisfactorily.

PMID- 12224627
TI  - 2-[3-(2-Thioxopyrrolidin-3-ylidene)methyll-tryptophan, a novel yellow pigment in
      salted radish roots.
AB  - The structure of the yellow pigment found in salted radish roots was studied. It
      was found that 1-(2-thioxopyrrolidin-3-yl)-1,2,3,4-tetrahydro-beta-carboline-3
      carboxylic acid (TPCC) was unstable under neutral pH, and was easily converted
      into the yellow pigment. The yellow pigment was isolated and identified as 2-[3
      (2-thioxopyrrolidin-3-ylidene)methyl]-tryptophan (TPMT) by IR, MS, 1H-, and 13C
      NMR spectroscopy. In addition, we proved that this compound was the main yellow
      pigment in salted radish roots. This compound induced no mutagenicity in
      Salmonella typhimurium TA98 and TA100, either with or without prior activation.

PMID- 12224628
TI  - Changes in activity coefficient gamma(w) of water and the foaming capacity of
      protein during hydrolysis.
AB  - The changes in the interaction between food proteins and water and in their
      surface functional property during enzymatic hydrolysis were investigated.
      Ovalbumin, a soy protein isolate (SPI), and casein were hydrolyzed with trypsin,
      and the degree of hydrolysis, water activity a(w), and foaming capacity of each
      hydrolysate were measured. Ovalbumin showed the minimum value for a(w), and the
      values for SPI and casein progressively decreased during hydrolysis. Therefore,
      the activity coefficient of water, gamma(w) (=a(w)/x(w), where x(w) is the mole
      fraction of water) was obtained to remove the influence of mole change and to
      examine the interaction of protein hydrolysates with water. In order to calculate
      x(w) in a sample during protein hydrolysis, a method for roughly estimating the
      number of moles of the protein hydrolysate in a solution was developed. The
      strategy was to modify the TNBS (2,4,6-trinitrobenzenesulfonic acid) method and
      to combine this method with the modified Ellman method and the determination of
      lysine by an amino acid analyzer. During enzymatic hydrolysis, each protein
      sample showed a minimum gamma(w) value and maximum foaming capacity.

PMID- 12224629
TI  - Isolation and characterization of dibenzofuran-degrading actinomycetes: analysis
      of multiple extradiol dioxygenase genes in dibenzofuran-degrading Rhodococcus
      species.
AB  - Sixteen actinomycetes capable of utilizing dibenzofuran as a sole source of
      carbon and energy were isolated, including Rhodococcus, Microbacterium, and
      Terrabacter genera. Heretofore, no dibenzofuran-utilizing strain belonging to the
      genus Microbacterium has been reported. Five extradiol dioxygenase genes (dfdB,
      and edil to 4) of the strain Rhodococcus sp. YK2 were cloned and analyzed. The
      nucleotide sequence of dfdB gene was almost identical to the bphC1 gene of
      Terrabacter sp. DPO360, which was involved in dibenzofuran metabolism in this
      strain. Southern and Northern hybridization analyses using these extradiol
      dioxygenase genes as probes suggest that the dfdB gene in YK2 was conserved in
      diverse dibenzofuran-utilizing actinomycetes; also, the dfdB gene was the only
      expressed gene among five extradiol dioxygenase genes in the medium containing DF
      as a sole carbon source. These results suggest that the dfdB gene is important
      for dibenzofuran metabolism not only in the strain YK2, but also in diverse
      dibenzofuran-degrading actinomycetes.

PMID- 12224630
TI  - Phenotype of hepatocyte spheroids in Arg-GLY-Asp (RGD) containing a thermo
      reversible extracellular matrix.
AB  - The spheroid of specific cells is often regarded as the better form in artificial
      organs and mammalian cell bioreactors for improved cell-specific functions. In
      this study, freshly harvested primary rat hepatocytes, which had been cultivated
      as spheroids and entrapped in a synthetic thermo-reversible extracellular matrix,
      were examined for differentiated morphology and enhanced liver-specific functions
      as compared to a control set (hepatocytes in single-cell form). A copolymer of N
      isopropylacrylamide (98 mole % in the feed) and acrylic acid (poly(NiPAAm-co
      AAc)), and the adhesion molecule, an Arg-Gly-Asp (RGD)-incorporated thermo
      reversible matrix, were used to entrap hepatocytes in the form of either
      spheroids or single cells. In a 28-day culture period, the spheroids in the RGD
      incorporated gel maintained higher viability and produced albumin and urea at
      constant rates, while there was lower cell viability and less albumin secretion
      by the spheroids in p(NiPAAm-co-AAc). Hepatocytes cultured as spheroids in the
      RGD-incorporated gel would constitute a potentially useful three-dimensional cell
      system for application in a bio-artificial liver device.

PMID- 12224631
TI  - Relationship between estrogen receptor-binding and estrogenic activities of
      environmental estrogens and suppression by flavonoids.
AB  - In this study, we investigated the estrogenic activity of environmental estrogens
      by a competition binding assay using a human recombinant estrogens receptor
      (hERbeta) and by a proliferation assay using MCF-7 cells and a sulforhodamine-B
      assay. In the binding assay, pharmaceuticals had a stronger binding activity to
      hERbeta than that of some phytoestrogens (coumestrol, daidzein, genistein,
      luteolin, chrysin, flavone, and naringenin) or industrial chemicals, but
      phytoestrogens such as coumestrol had a binding activity as strong as
      pharmaceuticals such as 17alpha-ethynylestradiol (EE), tamoxifen (Tam), and
      mestranol. In the proliferation assay, pharmaceuticals such as
      diethylstilbestrol, EE, Tam, and clomiphene, and industrial chemicals such as 4
      nonylphenol, bisphenol A, and 4-dihydroxybiphenyl had a proliferation-stimulating
      activity as strong as 17beta-estradiol (ES). In addition, we found that
      phytoestrogens such as coumestrol, daidzein, luteolin, and quercetin exerted a
      proliferation stimulating activity as strong as ES. Furthermore, we examined the
      suppression of proliferation-stimulating activity, induced by environmental
      estrogen, by flavonoids, such as daidzein, genistein, quercetin, and luteolin,
      and found that these flavonoids suppressed the induction of the proliferation
      stimulating activity of environmental estrogens. The suppressive effect of
      flavonoids suggests that these compounds have anti-estrogenic and anti-cancer
      activities.

PMID- 12224632
TI  - Foreign insect hormones stimulating the transcription of the ie-1 promoter of
      Bombyx mori nuclear polyhedrosis virus in vivo and in vitro.
AB  - Via a transient expression assay system, an experimental study was undertaken to
      characterize the effects of insect ecdysone and juvenile hormone analogue on the
      transient expression of the luciferase gene under the control of the immediate
      early gene (ie-1) promoter of Bombyx mori nuclear polyhedrosis virus. The results
      demonstrated that the transcriptional activity of the ie-1 promoter was increased
      to a certain extent by different insect hormone treatments in uninfected insect
      cells or fifth instar silkworm larvae transfected with a plasmid containing a
      luciferase gene driven by the ie-1 promoter. By ecdysone treatment alone, an
      increase of 5-7 fold was reached in Bm-N, or Bm-5 cells, or in the early
      developmental stage of fifth instar larvae. By treatment with juvenile hormone
      analogue alone, about 2-fold, in Bm-N, Bm-5, and Sf-21 cells, or about 5-fold
      increase in the middle developmental stage of larvae was given, respectively. By
      co-treatment with ecdysone and juvenile hormone analogue, the incease was given
      between that of ecdysone and juvenile hormone analogue treatment alone. In
      addition, the synergistic effects of foreign/endogenous hormones on the activity
      of ie-1 promoter are discussed.

PMID- 12224633
TI  - Synthesis of 1,2-oxygenated 6-arylfurofuran lignan: stereoselective synthesis of
      (1S,2S,5R,6S)-1-hydroxysamin.
AB  - (1S,2S,5R,6S)-6-(3,4-Methylenedioxyphenyl)-3,7-dioxabicyclo[3.3.0]octan-1,2-diol
      ((+)-1-hydroxysamin 1) was synthesized, starting from olefin 8. Stereoselective
      alpha-hydroxylation was achieved after converting 8 to aldehyde 13. Resulting
      unstable alpha-hydroxy aldehyde 14 was then transformed to (+)-1-hydroxysamin
      (1). This is a new efficient synthetic route to 1,2-oxygenated 6-arylfurofuran
      lignans.

PMID- 12224634
TI  - Recognition of a cysteine substrate by E. coli gamma-glutamylcysteine synthetase
      probed by sulfoximine-based transition-state analogue inhibitors.
AB  - A series of sulfoximine-based transition-state analogue inhibitors with a varying
      alkyl side chain was synthesized to probe the recognition of a Cys substrate by
      E. coli gamma-glutamylcysteine synthetase (gamma-GCS). The sulfoximines with a
      small alkyl group (H, methyl, ethyl, propyl, butyl and CH2OH) each served as a
      slow-binding inhibitor, the sulfoximine with an ethyl being by far the most
      potent inhibitor to cause facile and irreversible enzyme inhibition. As the size
      of the side chain changed from an ethyl, the inhibition potency markedly
      decreased to reduce the overall affinity with concomitant loss in the
      inactivation rate and with facile enzyme reactivation by dilution. The
      sulfoximine without a side chain inhibited the enzyme with almost the same
      potency as that of L-buthionine-(SR)-sulfoximine (BSO). The free energy
      difference calculated from the inhibition constants indicates that the side chain
      of Cys was recognized by its size through hydrophobic interaction and contributed
      almost equally or even more than the carboxy group to the overall binding of Cys
      in the transition state.

PMID- 12224635
TI  - Guanosine 5'-diphosphate 3'-diphosphate (ppGpp) synthetic activities on
      Escherichia coli SpoT domains.
AB  - Escherichia coli SpoT protein, with 702 amino acid residues, is a bifunctional
      enzyme catalyzing both guanosine 5'-diphosphate 3'-diphosphate (ppGpp)
      degradation and its synthesis. First, we investigated how many domains are
      included in SpoT protein, by limited hydrolysis of the protein with serine
      proteases, alpha-chymotrypsin, and elastase. Based on the results, we deduced
      that SpoT protein is composed of two major domains, an N-terminal half domain
      from Met1 to Phe373 and a C-terminal half domain from Glu374 to Asn702 (C
      terminal end). In addition, by a further alpha-chymotrypsin digestion, two
      cleaved sites were found at Arg196 in the N-terminal half domain (D12) and at
      Lys475 in the C-terminal half domain (D34), to produce four minor domains, D1,
      D2, D3, and D4. Next, plasmids expressing the two major domains (D12 and D34) and
      four minor domains (D1, D2, D3, and D4) were constructed. Consequently, the
      deduced SpoT minor domains as well as the major domains were expressed as stable
      protein units, except for D4. D4 may also be folded into a stable protein in E.
      coli cells, since high expression of D4 from a plasmid results in host cell
      lethality. E. coli relA -, spoT- double null strains expressing D1, D2, and D12
      recovered cell growth in M9 minimal medium, but the transformants of D3, D4, and
      D34 did not grow in the minimal medium. This indicates that ppGpp synthetic
      activities could be restricted in the N-terminal half domain (D12, D1, and D2).

PMID- 12224636
TI  - Structural analysis of an extracellular polysaccharide bioflocculant of
      Klebsiella pneumoniae.
AB  - The glycoside composition and sequence of an extracellular polysaccharide
      flocculant of Klebsiella pneumoniae H12 was analyzed. GC and HPLC analysis of the
      acid-hydrolysate identified its constituent monosaccharides as D-Glc, D-Man, D
      Gal, and D-GlcA in an approximate molar ratio of 3.9:1.0:2.3:3.6. To analyze the
      glycoside sequence, the polysaccharide was partially hydrolyzed by acid and
      enzyme treatment. GC, HPLC, TLC, MALDI-TOF/MS, and 1H- and 13C- NMR spectroscopy
      characterized the obtained oligosaccharides. The results clarified the partial
      structure of H12 polysaccharide as a linear polymer of a unit of pentasaccharide
      with a side chain of one D-GlcA to D-Glc moiety (see below). Although the
      existence of other sequences or other constituent glycosides could not be fully
      excluded, H12 polysaccharide must be a novel types as such a complicated unit for
      a polymer has not so far been reported. The partial structure of a H12
      polysaccharide flocculant is also discussed in this report. [structure: see text]

PMID- 12224637
TI  - Synthesis of (2S,2'R,3S,4R)-2-(2'-hydroxy-21'-methyidocosanoylamino)-1,3,4
      pentadecanetriol, the ceramide sex pheromone of the female hair crab, Erimacrus
      isenbeckii.
AB  - The ceramide sex pheromone [(2S,2'R,3S,4R)-2-(2'-hydroxy-21
      methyldocosanoylamino)-1,3,4-pentadecanetriol (1)] of the female hair crab
      (Erimacrus isenbeckii) was synthesized by starting from (S)-serine and 12-bromo-1
      dodecanol.

PMID- 12224638
TI  - Significance of the 20-kDa subunit of heterodimeric 2-deoxy-scyllo-inosose
      synthase for the biosynthesis of butirosin antibiotics in Bacillus circulans.
AB  - A gene (btrC2) encoding the 20-kDa subunit of 2-deoxy-scyllo-inosose (DOI)
      synthase, a key enzyme in the biosynthesis of 2-deoxystreptamine, was identified
      from the butirosin-producer Bacillus circulans by reverse genetics. The deduced
      amino acid sequence of BtrC2 closely resembled that of YaaE of B. subtilis, but
      the function of the latter has not been known to date. Instead, BtrC2 appeared to
      show sequence similarity to a certain extent with HisH of B. subtilis, an
      amidotransferase subunit of imidazole glycerol phosphate synthase. Disruption of
      btrC2 reduced the growth rate compared with the wild type, and simultaneously
      antibiotic producing activity was lost. Addition of NH4Cl to the medium
      complemented only the growth rate of the disruptant, and both the growth rate and
      antibiotic production were restored by addition of yeast extract. In addition, a
      heterologous co-expression system of btrC2 with btrC was constructed in
      Escherichia coli. The simultaneously over-expressed BtrC2 and BtrC constituted a
      heterodimer, the biochemical features of which resembled those of DOI synthase
      from B. circulans more than those of the recombinant homodimeric BtrC. Despite
      the similarity of BtrC2 to HisH the heterodimer showed neither aminotransfer nor
      amidotransfer activity for 2-deoxy-scyllo-inosose as a substrate. All the
      observations suggest that BtrC2 is involved not only in the secondary metabolism,
      but also in the primary metabolism in B. circulans. The function of BtrC2 in the
      butirosin biosynthesis appears to be indirect, and may be involved in
      stabilization of DOI synthase and in regulation of its enzyme activity.

PMID- 12224639
TI  - Structural analysis of the extracellular polysaccharide produced by Sphaerotilus
      natans.
AB  - An extracellular polysaccharide (EPS) was recovered and purified from the culture
      fluid of a sheathed bacterium, Sphaerotilus natans. Glucose, rhamnose, and
      aldobiouronic acid were detected in the acid hydrolysate of EPS by thin-layer
      chromatography (TLC). The aldobiouronic acid was found to be composed of
      glucuronic acid and rhamnose by TLC and gas-liquid chromatography analyses of the
      corresponding neutral disaccharide. The structure of EPS was identified by
      methylation linkage analysis and nuclear magnetic resonance. Additionally,
      partial acid hydrolysates of EPS were prepared and put through fast atom
      bombardment-mass spectrometry to determine the sugar sequence of EPS. The
      resulting data showed that EPS produced by S. natans is a new gellan-like
      polysaccharide constructed from a tetrasaccharide repeating unit, as shown below.
      -->4)-alpha-D-Glcp-(1-->2)-beta-D-GlcA p-(1-->2)-alpha-L-Rha p-(1-->3)-beta-L-Rha
      p-(1-->.

PMID- 12224640
TI  - Alpha-glucosidase inhibitory activity of a 70% methanol extract from ezoishige
      (Pelvetia babingtonii de Toni) and its effect on the elevation of blood glucose
      level in rats.
AB  - The 70% methanol extract from ezoishige (Pelvetia babingtonii de Toni) inhibited
      the rat-intestinal alpha-glucosidase, sucrase and maltase activities, with IC50
      values of 2.24 and 2.84 mg/ml. Sucrose was orally administered with or without
      the extract to rats at 1000 mg/kg. The postprandial elevation in the blood
      glucose level at 15 and 30 min after the administration of sucrose with the
      extract was significantly suppressed when compared with the control. These
      results suggest that the extract from ezoishige has potent alpha-glucosidase
      inhibitors and would be effective for suppressing postprandial hyperglycemia.

PMID- 12224641
TI  - Production of long-chain levan by a sacC insertional mutant from Bacillus
      subtilis 327UH.
AB  - A hyper extracellular protein producer, Bacillus subtilis 327UH, produced large
      amounts of levan in a medium containing 20% sucrose, and the yield of levan after
      10 hours was more than 60%, when based on the fructose amount of sucrose. After
      transformation of 327UH with a levanase-deficient 168SC (sacC::Cm(r)) chromosomal
      DNA, a Cm(r) transformant 327UHSC (sacC::Cm(r) degSU(Hy)) produced 3 times longer
      levan than that of the wild type.

PMID- 12224642
TI  - Effect of tea catechins on cellular lipid peroxidation and cytotoxicity in HepG2
      cells.
AB  - Tea catechins inhibited TBARS accumulation in HepG2 cells, the order of
      effectiveness being (-)-epigallocatechin gallate (EGCG) > (-)-epigallocatechin
      (EGC) > or = (-)-epicatechin gallate (ECG) > (-)-epicatechin (EC). EGCG and EGC
      protected the depletion of alpha-tocopherol in the cells, and the glutathione
      content was enhanced by all four catechins. Moreover, all four catechins
      suppressed the formation of glutathione disulfide and the activation of
      glutathione peroxidase induced by tert-butylated hydroperoxide.

PMID- 12224643
TI  - Total DNA preparation excluding extracellular acidic polysaccharide from
      Lipomyces yeasts and its application to taxonomic studies.
AB  - A preparation method of total DNA from Lipomyces yeasts was improved in order to
      exclude extracellular acidic polysaccharide thoroughly. The method combined an
      ultracentrifuge and polyethylene glycol precipitation with the usual method. The
      total DNAs obtained were analyzed for G + C content and by DNA-DNA hybridization.
      The results all agreed almost completely with literature data. All the DNA
      samples prepared using this method were pure enough for these taxonomic analyses
      and could also be used as templates of PCR for amplification of small subunit
      ribosomal DNA and the internal transcribed spacer region.

PMID- 12224644
TI  - Structure of genes for Hsp30 from the white-rot fungus Coriolus versicolor and
      the increase of their expression by heat shock and exposure to a hazardous
      chemical.
AB  - We isolated and analysed two genomic DNAs that encode the heat-shock protein
      Hsp30 from Coriolus versicolor. The amino acid sequences substitute only three
      amino acid substitutions. The promoter regions contain the consensus heat-shock
      element, a xenobiotic-response element, a stress-response element, and a metal
      response element. The levels of mRNAs for Hsp30 increased markedly after exposure
      of C. versicolor to pentachlorophenol and levels were higher than those after
      heat shock.

PMID- 12224645
TI  - Isolation and measurement of quercetin glucosides in flower buds of Japanese
      butterbur (Petasites japonicus subsp. gigantea Kitam.).
AB  - Three quercetin glucosides were isolated from flower buds of Japanese butterbur
      (Petasites japonicus subsp. gigantea Kitam.) together with caffeic acid as the
      ingredients that had DPPH radical scavenging activity, using the DPPH-HPLC method
      for measuring the radical scavenging activity. These quercetin glucosides were
      identified as quercetin 3-O-beta-D-glucoside, quercetin 3-O-beta-D-6''-O
      acetylglucoside, and rutin, and the amounts of the glucosides in flower buds were
      also examined by HPLC. The flower buds were harvested from four different sites,
      the total amount of quercetin glucosides in each site was 100-170 mg/100 g fr.
      wt., and there were no great differences of the amounts between growing fields.

PMID- 12224647
TI  - Microbial degradation of lipid by Acinetobacter sp. strain SOD-1.
AB  - Acinetobacter sp. strain SOD-1, capable of rapidly degrading salad oil, was
      isolated from soil. Strain SOD-1 showed good growth and degraded 68.7+/-2.7 and
      83.0% of an initial 3000 ppm salad oil suspension in 24 h at 20 degrees C and pH
      7.0 and at 35 degrees C and pH 8.0, respectively. The degradation rate depended
      on pH, temperature, phosphate concentration, and initial cell density.

PMID- 12224646
TI  - Alpha-glucosidase inhibitor from the seeds of balsam pear (Momordica charantia)
      and the fruit bodies of Grifola frondosa.
AB  - Alpha-glucosidase inhibitory activities were found in aqueous methanol extracts
      of the seeds of Momordica charantia and the fruit bodies of Grifola frondosa. An
      active principle against the enzyme prepared from rat small intestine acetone
      powders was isolated and characterized. The structure of the isolated compound
      was identified as D-(+)-trehalose by FDMS, 1H-, 13C-NMR, and [alpha]D
      measurements. The inhibitory activity of trehalose was compared with 1
      deoxynojirimycin. Trehalose showed 45% inhibitory activity at the concentration
      of 2 x 10(-3) m, but 1-deoxynojirimycin had 52% inhibitory activity at 1 x 10(-7)
      M.

PMID- 12224648
TI  - DnaK chaperone machine and trigger factor are only partially required for normal
      growth of Bacillus subtilis.
AB  - While dnaK and tig are the essential components for nascent polypeptide folding
      in E. coli, deletion did not confer synthetic lethality in B. subtilis,
      suggesting that under normal growth conditions, another system or mechanism with
      a specific role prevails. Likewise, survival at high temperature suffered
      dramatically, resulting from deletion of several sets of heat shock genes, thus
      during sudden stress various heat shock genes act synergistically to protect the
      proteins.

PMID- 12224649
TI  - Cloning and expression of the exo-beta-D-1,3-glucanase gene (exgS) from
      Aspergillus saitoi.
AB  - A gene of exo-1,3-beta-D-glucanase (exgS) was cloned from a koji mold,
      Aspergillus saitoi, genomic DNA using PCR. The exgS has an ORF comprising 2832
      bp, which contains one intron of 45 bp, and encodes 945 amino acids. The deduced
      amino acid sequences showed that the ExgS has a non-homologous linker region
      consisting of 180 amino acids, which encompassed highly conserved regions
      observed in Exg homologues from filamentous fungi. A recombinant protein (ExgS)
      has been recovered from the cultural filtrate of an Aspergillus oryzae strain
      that carried an expression vector containing full length of the exgS. The N
      terminal amino acid sequences of the recombinant exo-1,3-beta-D-glucanase (ExgS)
      were identical to that of native ExgS from A. saitoi.

PMID- 12224650
TI  - Synthesis of the (17R)- and (17S)-isomers of volicitin, an elicitor of plant
      volatiles contained in the oral secretion of the beet armyworm.
AB  - Both the (17R)- and (17S)-isomers of volicitin, which is contained in the oral
      secretion of the beet armyworm and induces corn seedlings to emit a blend of
      volatile compounds to attract the natural enemy of the herbivore, were
      synthesized via the semi-hydrogenation of an intermediary diyne and (Z)-selective
      olefination as the key steps. They were both obtained as crystalline compounds.

PMID- 12224651
TI  - Isolation of Enterococcus hirae mutant deficient in low-affinity potassium uptake
      at alkaline pH.
AB  - We here isolated an Enterococcus hirae mutant unable to grow well at pH 10. The
      influx rate calculated from steady-state 42K+/K+ exchange and the intracellular
      K+ concentration of the mutant were reduced to 53 and 55% of those of the wild
      type, respectively. The activities of two high-affinity K+ uptake systems, KtrI
      and KtrII, were normal in the mutant, but the kinetics of net K+ uptake at pH 10
      indicated that a low-affinity K+ uptake with a Km of about 20 mM (Kawano, M,
      Abuki, R, Igarashi, K, Kakinuma, Y. (2001) Arch. Microbiol. 175: 41-45), which
      were seen in the wild-type, was deficient in this mutant.

PMID- 12224652
TI  - A highly sensitive assay for proteases using staphylococcal protein A fused with
      enhanced green fluorescent protein.
AB  - Enhanced green fluorescent protein (EGFP) was fused with staphylococcal protein A
      (SpA) and used as a substrate for proteases. An SpA-EGFP assay was done in three
      steps: (i) digestion of SpA-EGFP by proteases, (ii) addition of rabbit IgG
      immobilized on Sepharose beads, and (iii) measurement of the fluorescence
      intensity of supernatant. The assay was sensitive enough to measure picogram
      levels of trypsin and chymotrypsin, and may be applicable to various other
      proteases as one of the most sensitive methods.

PMID- 12224654
TI  - Suppressive effect of polysaccharides from the edible and medicinal mushrooms,
      Lentinus edodes and Agaricus blazei, on the expression of cytochrome P450s in
      mice.
AB  - To investigate the effects of lentinan from Lentinas edodes and polysaccharides
      from Agaricus blazei (ABPS) on the expression of cytochrome P450s (CYPs),
      lentinan (10 mg/kg/day) or ABPS (200 mg/kg/day) was administered to female BALB/c
      mice four times every other day by intraperitoneal injection. Lentinan and ABPS
      suppressed both the constitutive and 3-methylcholanthrene-induced CYP1A
      expression and ethoxyresorufin-O-deethylation activity in the liver.

PMID- 12224653
TI  - Effects of dietary eritadenine on delta6-desaturase activity and fatty acid
      profiles of several lipids in rats fed different fats.
AB  - Effects of dietary eritadenine on liver microsomal delta6-desaturase activity and
      the fatty acid profile of phosphatidylcholine, cholesteryl esters, and
      triglycerides of liver microsomes or plasma were investigated in rats fed
      different fats (palm oil, olive oil, and safflower oil). The activity of delta6
      desaturase was influenced by both dietary fat types and eritadenine. In rats fed
      control diets, delta6-desaturase activity was higher in the order of the palm
      oil, olive oil, and safflower oil groups. In rats fed eritadenine-supplemented
      diets, the enzyme activity was markedly decreased to a constant level
      irrespective of dietary fat type. The 20:4n-6/18:2n-6 ratio of
      phosphatidylcholine and cholesteryl esters, as compared with triglycerides, was
      highly sensitive to eritadenine. The results suggest that the activity of delta6
      desaturase is regulated by dietary fats and eritadenine independently, and that
      the effect of eritadenine is stronger than that of dietary fats.

PMID- 12224655
TI  - Binding selectivity of conformationally restricted analogues of (-)-indolactam-V
      to the C1 domains of protein kinase C isozymes.
AB  - Two conformationally restricted analogues of (-)-indolactam-V (1) (cis and trans
      amides) were examined for their binding selectivity to the synthetic C1 peptides
      of all protein kinase C (PKC) isozymes. Although the binding constants of the cis
      amide-restricted analogue (2) were equal to those of 1, the trans amide
      restricted analogue (3) bound significantly only to the novel PKC (delta,
      epsilon, eta, theta) isozymes.

PMID- 12224656
TI  - Overweight children and adolescents: description, epidemiology, and demographics.
AB  - We describe prevalence and trends in overweight among children and adolescents (6
      to 17 years old) in the US population and variation in the prevalence by sex,
      age, race-ethnicity, income, and educational level. Height and weight were
      measured in nationally representative surveys conducted between 1963 and 1994:
      cycles II (1963 to 1965) and III (1966 to 1970) of the National Health
      Examination Survey (NHES) and the National Health and Nutrition Examination
      Surveys (NHANES I, 1971 to 1974; NHANES II, 1976 to 1980; and NHANES III, 1988 to
      1994). Overweight was defined by the age- and sex-specific 95th percentile of
      body mass index (BMI) from NHES II and III. BMI values between the 85th and 95th
      percentiles were considered an area of concern, because at this level there is
      increased risk for becoming overweight. Approximately 11% of children and
      adolescents were overweight in 1988 to 1994, and an additional 14% had a BMI
      between the 85th and 95th percentiles. The prevalence of overweight did not vary
      systematically with race-ethnicity, income, or education. Overweight prevalence
      increased over time, with the largest increase between NHANES II and NHANES III.
      Examination of the entire BMI distribution showed that the heaviest children were
      markedly heavier in NHANES III than in NHES, but the rest of the distribution of
      BMI showed little change. Data are limited for assessing the causes of the rapid
      change in the prevalence of overweight. The increased overweight prevalence in US
      children and adolescents may be one manifestation of a more general set of
      societal effects. Childhood overweight should be addressed from a public health
      perspective.

PMID- 12224657
TI  - Measurement issues related to studies of childhood obesity: assessment of body
      composition, body fat distribution, physical activity, and food intake.
AB  - This article reviews the current status of various methodologies used in obesity
      and nutrition research in children, with particular emphasis on identifying
      priorities for research needs. The focus of the article is 1) to review
      methodologic aspects involved with measurement of body composition, body-fat
      distribution, energy expenditure and substrate use, physical activity, and food
      intake in children; and 2) to present an inventory of research priorities.

PMID- 12224658
TI  - Health consequences of obesity in youth: childhood predictors of adult disease.
AB  - Obesity now affects one in five children in the United States. Discrimination
      against overweight children begins early in childhood and becomes progressively
      institutionalized. Because obese children tend to be taller than their
      nonoverweight peers, they are apt to be viewed as more mature. The inappropriate
      expectations that result may have an adverse effect on their socialization. Many
      of the cardiovascular consequences that characterize adult-onset obesity are
      preceded by abnormalities that begin in childhood. Hyperlipidemia, hypertension,
      and abnormal glucose tolerance occur with increased frequency in obese children
      and adolescents. The relationship of cardiovascular risk factors to visceral fat
      independent of total body fat remains unclear. Sleep apnea, pseudotumor cerebri,
      and Blount's disease represent major sources of morbidity for which rapid and
      sustained weight reduction is essential. Although several periods of increased
      risk appear in childhood, it is not clear whether obesity with onset early in
      childhood carries a greater risk of adult morbidity and mortality. Obesity is now
      the most prevalent nutritional disease of children and adolescents in the United
      States. Although obesity-associated morbidities occur more frequently in adults,
      significant consequences of obesity as well as the antecedents of adult disease
      occur in obese children and adolescents. In this review, I consider the adverse
      effects of obesity in children and adolescents and attempt to outline areas for
      future research. I refer to obesity as a body mass index greater than the 95th
      percentile for children of the same age and gender.

PMID- 12224659
TI  - The physiology of body weight regulation: relevance to the etiology of obesity in
      children.
AB  - The prevalence of obesity in children and adults in the United States has
      increased by more than 30% over the past decade. Recent studies of the physiology
      and molecular genetics of obesity in humans have provided evidence that body
      weight (fat) is regulated. Some of the genes encoding the molecular components of
      this regulatory system have been isolated from rodents. The increasing prevalence
      of obesity in the United States apparently represents the interaction of these
      genes with an environment that encourages a sedentary lifestyle and consumption
      of calories. The rapid increase in the prevalence of obesity emphasizes the role
      of environmental factors, because genetic changes could not occur at this rate.
      Thus, understanding of the relevant genes and how their effects are mediated by
      environment and development should lead to more effective prophylaxis and therapy
      of obesity. Although no clear environmental factors have been identified as
      causative of obesity, the rapid increases in the prevalence of obesity and the
      seeming voluntary immutability of adult body fatness can be taken as tacit
      evidence that the pediatric environment can be altered in a way that affects
      adult body weight.

PMID- 12224660
TI  - Development of eating behaviors among children and adolescents.
AB  - The prevalence of obesity among children is high and is increasing. We know that
      obesity runs in families, with children of obese parents at greater risk of
      developing obesity than children of thin parents. Research on genetic factors in
      obesity has provided us with estimates of the proportion of the variance in a
      population accounted for by genetic factors. However, this research does not
      provide information regarding individual development. To design effective
      preventive interventions, research is needed to delineate how genetics and
      environmental factors interact in the etiology of childhood obesity. Addressing
      this question is especially challenging because parents provide both genes and
      environment for children. An enormous amount of learning about food and eating
      occurs during the transition from the exclusive milk diet of infancy to the
      omnivore's diet consumed by early childhood. This early learning is constrained
      by children's genetic predispositions, which include the unlearned preference for
      sweet tastes, salty tastes, and the rejection of sour and bitter tastes. Children
      also are predisposed to reject new foods and to learn associations between foods'
      flavors and the postingestive consequences of eating. Evidence suggests that
      children can respond to the energy density of the diet and that although intake
      at individual meals is erratic, 24-hour energy intake is relatively well
      regulated. There are individual differences in the regulation of energy intake as
      early as the preschool period. These individual differences in self-regulation
      are associated with differences in child-feeding practices and with children's
      adiposity. This suggests that child-feeding practices have the potential to
      affect children's energy balance via altering patterns of intake. Initial
      evidence indicates that imposition of stringent parental controls can potentiate
      preferences for high-fat, energy-dense foods, limit children's acceptance of a
      variety of foods, and disrupt children's regulation of energy intake by altering
      children's responsiveness to internal cues of hunger and satiety. This can occur
      when well-intended but concerned parents assume that children need help in
      determining what, when, and how much to eat and when parents impose child-feeding
      practices that provide children with few opportunities for self-control.
      Implications of these findings for preventive interventions are discussed.

PMID- 12224661
TI  - Development of physical activity behaviors among children and adolescents.
AB  - Physical activity is a key component of energy balance and is promoted in
      children and adolescents as a lifelong positive health behavior. Understanding
      the potential behavioral determinants necessitates understanding influences from
      three fundamental areas: 1) physiologic and developmental factors, 2)
      environmental factors, and 3) psychological, social, and demographic factors. The
      literature to date has generally investigated potential predictors of physical
      activity in children and adolescents in each of these three general areas,
      although existing data rely largely on cross-sectional studies in which it is
      difficult to distinguish a determinant from a correlate. In all likelihood,
      aspects of each of these three areas interact in a multidimensional way to
      influence physical activity in youth. This article reviews evidence of potential
      determinants of physical activity in children and adolescents and provides
      recommendations for future work.

PMID- 12224662
TI  - Treatment of pediatric obesity.
AB  - The primary goal of childhood obesity interventions is regulation of body weight
      and fat with adequate nutrition for growth and development. Ideally, these
      interventions are associated with positive changes in the physiologic and
      psychological sequelae of obesity. To contribute to long-term weight maintenance,
      interventions should modify eating and exercise behaviors such that new,
      healthier behaviors develop and replace unhealthy behaviors, thereby allowing
      healthier behaviors to persist throughout development and into adulthood. This
      overview of pediatric obesity treatment, using predominantly randomized,
      controlled studies, highlights important contributions and developments in
      primarily dietary, activity, and behavior change interventions, and identifies
      characteristics of successful treatment and maintenance interventions. Potential
      positive (eg, reduction in blood pressure, serum lipids, and insulin resistance)
      and negative (eg, development of disordered eating patterns) side effects of
      treatment also are described. Recommendations for improving implementation of
      childhood obesity treatments, including application of behavioral choice theory,
      improving knowledge of response extinction and recovery in regards to behavior
      relapse, individualization of treatment, and integration of basic science with
      clinical outcome research, are discussed.

PMID- 12224663
TI  - Childhood obesity: future directions and research priorities.
AB  - The threat of obesity is greater than ever for US children and adolescents. All
      indications are that the current generation of children will grow into the most
      obese generation of adults in US history. Furthermore, there is every expectation
      that the next generation of children is likely to be fatter and less fit than the
      current generation. Despite the recognition of the severe health and psychosocial
      damage done by childhood obesity, it remains low on the public agenda of
      important issues facing policy makers. Perhaps this is because the most serious
      health effects of obesity in today's children will not be seen for several
      decades. Action must be taken now to stem the epidemic of childhood obesity. This
      action will require a prioritization of research into the etiology, treatment,
      and prevention of childhood obesity. It is unlikely that sufficient resources for
      such research will be available from public and private sources until the issue
      of childhood obesity is moved higher on the public agenda.

PMID- 12224664
TI  - Ipratropium bromide in acute asthma exacerbation.

PMID- 12224665
TI  - Cutaneous injections of sterile water for the relief of labor pain.

PMID- 12224666
TI  - Quality of life and therapy in type 2 diabetes.

PMID- 12224667
TI  - Zanamivir in the prevention of influenza among healthy adults.

PMID- 12224668
TI  - Aggressive lipid-lowering in stable patients with coronary artery disease.

PMID- 12224669
TI  - Effect of systemic glucocorticoids on exacerbations of chronic obstructive
      pulmonary disease.

PMID- 12224670
TI  - How important is mitral valve prolapse?

PMID- 12224671
TI  - Spironolactone for congestive heart failure.

PMID- 12224672
TI  - Treating heart failure in primary care.

PMID- 12224673
TI  - Does managed care restrictiveness affect the perceived quality of primary care? A
      report from ASPN. Ambulatory Sentinel Practice Network.
AB  - BACKGROUND: The competitive managed care marketplace is causing increased
      restrictiveness in the structure of health plans. The effect of plan
      restrictiveness on the delivery of primary care is unknown. Our purpose was to
      examine the association of the organizational and financial restrictiveness of
      managed care plans with important elements of primary care, the patient-clinician
      relationship, and patient satisfaction. METHODS: We conducted a cross-sectional
      study of 15 member practices of the Ambulatory Sentinel Practice Network selected
      to represent diverse health care markets. Each practice completed a Managed Care
      Survey to characterize the degree of organizational and financial restrictiveness
      for each individual health care plan. A total of 199 managed care plans were
      characterized. Then, 1475 consecutive outpatients completed a patient survey that
      included: the Components of Primary Care Instrument as a measure of attributes of
      primary care; a measure of the amount of inconvenience involved with using the
      health care plan; and the Medical Outcomes Study Visit Rating Form for assessing
      patient satisfaction. RESULTS: Clinicians' reports of inconvenience were
      significantly associated (P < .001) with the financial and organizational
      restrictiveness scores of the plan. There was no association between plan
      restrictiveness and patient report of multiple aspects of the delivery of primary
      care or patient satisfaction with the visit. CONCLUSIONS: Plan restrictiveness is
      associated with greater perceived hassle for clinicians but not for patients.
      Plan restrictiveness seems to be creating great pressures for clinicians, but is
      not affecting patients' reports of the quality of important attributes of primary
      care or satisfaction with the visit. Physicians and their staffs appear to be
      buffering patients from the potentially negative effects of plan restrictiveness.

PMID- 12224674
TI  - Does the severity of mood and anxiety symptoms predict health care utilization?
AB  - BACKGROUND: Traditional diagnostic criteria for depression and anxiety fail to
      account for symptom severity. We previously evaluated a severity-based
      classification system of mood and anxiety symptoms. This study examines whether
      those severity groups are predictive of differences in health care utilization.
      METHODS: We used a cohort design to compare the health care utilization of 1232
      subjects classified into 4 groups according to symptom severity. Health care
      billing data were evaluated for each subject for a 15-month period around the
      index visit. Multiple linear regression models were used to examine relative
      contributions of individual variables to differences in health care utilization.
      Analysis of variance procedures were used to compare charges among the severity
      groups after adjusting for demographic and medical comorbidity variables.
      RESULTS: After adjustment, significant differences in health care utilization
      between groups were seen in all but 3 of the 15 months studied. Also, after
      adjustment, the presence of a mood or anxiety disorder influenced utilization for
      only a 6-month period. At 9 to 12 months, subjects in the high-severity group
      showed a more than twofold difference in adjusted charges compared with the low
      severity group ($225.36 vs $94.37). CONCLUSIONS: Our severity-based
      classification predicts statistically and clinically significant differences in
      health care utilization over most of a 15-month period. Differences in
      utilization persist even after adjustment for medical comorbidity and significant
      demographic covariates. Our work lends additional evidence that beyond screening
      for the presence of mood and anxiety disorders, it is important to assess symptom
      severity in primary care patients. Further study directed toward developing
      effective methods of identifying patients with high levels of mood and anxiety
      symptom severity could result in significant cost savings.

PMID- 12224675
TI  - Is paracervical block safe and effective? A prospective study of its association
      with neonatal umbilical artery pH values.
AB  - BACKGROUND: Paracervical blocks (PCBs) relieve labor pain, but reports of
      associated complications have caused many physicians to question their safety.
      METHODS: We designed a prospective observational study to examine the association
      between PCBs and umbilical artery hydrogen ion concentration (pH) values. A total
      of 261 healthy women in labor were recruited from a community hospital.
      Physicians used 1% lidocaine for the PCBs. We used multivariate linear regression
      to model predictors of umbilical artery pH at birth. RESULTS: Of the women
      studied, 238 (91%) received analgesia during labor (nalbuphine, PCB, pudendal,
      caudal, or epidural). Of these, 126 (48%) received at least one PCB (191 were
      given), and 197 (76%) received at least one dose of nalbuphine (237 were given).
      Univariate analyses showed no significant differences in mean 1-minute Apgar
      scores, 5-minute Apgar scores, umbilical artery pH, resuscitation with oxygen by
      mask, or length of newborn stay according to either PCB or nalbuphine exposure.
      Factors significantly associated with lower umbilical artery pH in a linear
      regression analysis included longer second stage of labor (-0.032 pH units for
      each 1-hour increase; 95% confidence interval [CI], -.046 to -.018), pudendal
      block (-0.022; 95% CI, -.040 to -.004), intrauterine pressure catheter use (
      0.029; 95% CI, -0.053 to -.006), nuchal cord (-0.027; 95% CI, -.051 to -.004),
      and midforceps delivery (-0.080; 95% CI, -.159 to .000). Increasing maternal age
      and induction with either artificial rupture of membranes or gel were associated
      with higher umbilical artery pH values. CONCLUSIONS: After adjusting for other
      variables, neither PCB nor nalbuphine use were associated with umbilical artery
      pH at birth. PCBs using 1% lidocaine injected superficially should be considered
      a safe and effective form of obstetric analgesia. PCBs may be especially useful
      for women giving birth in hospitals where other obstetric anesthesia services are
      not readily available.

PMID- 12224676
TI  - The delivery of clinical preventive services: acute care intervention.
AB  - BACKGROUND: . Evidence-based clinical preventive services are underutilized. We
      explored the major factors associated with delivery of these services in a large
      physician-owned community-based group practice that provided care for both fee
      for-service (FFS) and health maintenance organization (HMO) patient populations.
      METHODS: We performed a cross-sectional audit of the computerized billing data of
      all adult outpatients seen at least once by any primary care provider in 1995 (N
      = 75,621). Delivery of preventive services was stratified by age, sex, visit
      frequency, insurance status (FFS or HMO), and visit type (acute care only or
      scheduled preventive visit). RESULTS: Insurance status and visit type were the
      strongest predictors of clinical preventive service delivery. Patients with FFS
      coverage received 6% to 13% (absolute difference) fewer of these services than
      HMO patients. Acute-care-only patients received 9% to 45% fewer services than
      patients who scheduled preventive visits. The combination of these factors was
      associated with profound differences. CONCLUSIONS: Having insurance to pay for
      preventive services is an important factor in the delivery of such care.
      Encouraging all patients to schedule preventive visits has been suggested as a
      strategy for increasing delivery, but that is not practical in this setting.
      Assessing the need for preventive services and offering them during acute care
      visits has equal potential for increasing delivery.

PMID- 12224678
TI  - Loneliness as a predictor of hospital emergency department use.
AB  - BACKGROUND: Recent studies indicate that loneliness is a significant risk factor
      for many ailments from colds to heart disease. If lonely patients are at greater
      risk for illness, then we might expect that they would use the emergency
      department (ED) more often and incur greater medical costs than those who are not
      lonely. Our goal was to determine the prevalence of loneliness in patients in an
      ED and to evaluate it as a predictor of ED use, hospital admission, and chronic
      illness. METHODS: We evaluated a convenience sample of 164 ED patients with the
      University of California-Los Angeles Loneliness Scale, Version 3 and a survey of
      patient characteristics. Using medical record review and patient self-report, we
      determined total ED visits, the presence of chronic illness, and discharge
      diagnoses during a 1-year retrospective period. We evaluated data with least mean
      square regression and a 2-tailed t test. RESULTS: We found a statistically
      significant correlation between loneliness score and total hospital ED visits (P
      <.001). The mean loneliness score (39) was equal to that of normal populations.
      Patients scoring higher than the mean used the ED 60% more per year than patients
      who scored lower (P = .008). There was no association between a patient's
      loneliness score and baseline chronic illness or severity of current illness (P =
      .56). Spanish-speaking patients had higher loneliness scores than English
      speaking patients (P = .001). CONCLUSION: Loneliness is a predictor of hospital
      ED use independent of chronic illness and is potentially very expensive to
      society. We recommend further studies be done to examine if allocating resources
      for preventing, diagnosing, and treating loneliness would be cost effective.

PMID- 12224677
TI  - Heart failure in primary care: measuring the quality of care.
AB  - BACKGROUND: Concerns exist about the quality of care provided to heart failure
      patients by primary care physicians. Using an evidence-based clinical guideline,
      we evaluated the care given to patients with systolic heart failure. METHODS: We
      retrospectively reviewed the medical records of 420 patients from 25 primary care
      practices in upstate New York who had received a diagnosis of heart failure.
      Chart documentation confirmed the diagnosis (n = 395). We excluded patients with
      noncardiogenic volume overload or correctable valvular disease (n = 338).
      Performance profiles measured use of diagnostic tests, left ventricular ejection
      fraction (LVEF) measurement, patient education, and prescription of angiotensin
      converting enzyme (ACE) inhibitors. For treatment recommendations, patients were
      classified according to LVEF status. RESULTS: Only 82% of the patients studied
      had an LVEF test result documented in their charts. Of these, 49% had an LVEF <
      or = 40%. ACE inhibitor use was greater among patients with low LVEF (91%) than
      among those with a normal LVEF (62%). Among patients with systolic heart failure
      taking ACE inhibitors, 87% were at target doses. Adherence measures were low for
      laboratory evaluation and patient-education criteria. CONCLUSIONS: Heart failure
      with normal LVEF was as prevalent as systolic heart failure in these primary care
      practices. Performance profiles for the physicians' prescriptions of ACE
      inhibitors exceeded those published in the literature. Patients who did not have
      a documented measure of LVEF, however, received lower quality of care as measured
      by this disease-specific guideline. This underscores the importance of measuring
      LVEF.

PMID- 12224679
TI  - Diagnostic yield of screening for type 2 diabetes in high-risk patients: a
      systematic review.
AB  - OBJECTIVE: To determine the value of using risk factors to decide which patients
      should undergo serum screening for type 2 diabetes. SEARCH STRATEGIES: The
      MEDLINE and EMBASE electronic databases were searched for original studies of
      screening for type 2 diabetes on the basis of risk factors. The reference lists
      of all reviews, letters, editorials, consensus statements, and guidelines for
      diabetes screening were searched for additional studies. The Cochrane database
      was also searched for relevant reviews. SELECTION CRITERIA: All original studies
      regarding selective serum screening for type 2 diabetes on the basis of risk
      factors were included. review. Three studies were cross-sectional in design; 3
      employed survey data to develop computerized statistical models that used risk
      factors to identify cases of type 2 diabetes; and 1 used a similar method, but
      the resulting model was field tested in a separate population. No study describes
      a risk-factor-based method or instrument that helps substantially in the
      diagnosis of type 2 diabetes. CONCLUSIONS: Selective screening for type 2
      diabetes on the basis of risk factors cannot be recommended. Serum screening can
      be offered to patients who present with typical symptoms of diabetes.

PMID- 12224680
TI  - Management of mental disorders in rural primary care: a proposal for integrated
      psychosocial services.
AB  - Mental health facilities and specialized providers are particularly lacking in
      rural areas. Even when these are available, poverty, negative attitudes toward
      mental health treatments, and traditional rural values of privacy and autonomy
      often result in low utilization rates. Consequently, most mental health care in
      rural America is provided by primary care physicians who are also faced with
      competing demands, including tensions among limited time and resources, the
      multiple and complex needs of patients, and economic forces determining
      reimbursements. We propose that in the best interest of physicians and their
      patients, fully integrated psychosocial services in rural primary care settings
      would reduce the burden of time-consuming mental health care, conform to patient
      preference for immediate on-site care, reduce nonproductive medical care use, and
      eliminate duplication of effort by physicians and mental health professionals.
      The treatment model we propose would provide multiple arenas for psychosocial
      intervention - with the individual, the family, and the community - based on the
      patient's self-identified needs. The integration of psychosocial services within
      primary rural care is readily available, economically feasible, and urgently
      needed, but physicians must take the lead to implement this collaborative
      treatment partnership.

PMID- 12224681
TI  - Improving cessation rates?

PMID- 12224682
TI  - 'Angela's ashes' (lupus vulgaris: from yesterday to the third millennium).

PMID- 12224683
TI  - Uncommon manifestations of pemphigus vulgaris.

PMID- 12224684
TI  - Intrahepatic cholestasis of pregnancy: what's new.

PMID- 12224685
TI  - Sebaceus naevi: a clinicopathologic study.
AB  - OBJECTIVE: To analyse sebaceus naevus (SN) incidence, associated malignancies,
      and developmental defects in a retrospective study. METHODS: We retrospectively
      analysed all cases of SN excised in our Department over a 20-year period. All
      cases of epidermal naevus syndrome (Schimmelpenning syndrome) associated with SN
      were recorded, as well as all patients with histological changes suggesting
      degeneration of the initial SN. RESULT: A total 226 patients with SN were
      included in the study. Stage II was the most common (65%), and the parietal area
      was the most common location of SN (42%), with only 7% located in non-scalp
      areas. Syringocystadenoma papilliferum and trichoblastoma were the most common
      tumours arising on SN. We only found five patients with basal cell carcinoma
      arising on previous SN. Epidermal naevus syndrome associated with SN was
      diagnosed in 16 patients, and this was the most common neurocutaneous
      association. CONCLUSION: The incidence of malignancy arising on SN was very low,
      indicating that prophylactic surgery of NS in children is not recommendable.
      Developmental defects should be investigated in order to evidence possible
      epidermal naevus syndrome associated with SN.

PMID- 12224686
TI  - The role of psychological factors in palmoplantar pustulosis.
AB  - OBJECTIVE: The aim of the present study was to find out whether emotional stress
      is related to palmoplantar pustulosis (PPP). SUBJECTS AND METHODS: Our 21
      patients with palmoplantar pustulosis and 21 age- and sex-matched controls were
      studied with the help of a psychological interview and two psychological tests:
      Eysenk's Personality Questionnaire for Adults (EPQ-A) and Inventory of Situations
      and Response of Anxiety (ISRA). RESULTS: Anxiety, ranging from moderate to severe
      was higher in PPP patients than in controls (P < 0.001). CONCLUSION: Our findings
      seem to indicate that stress may be related to exacerbation of the palmoplantar
      pustulosis.

PMID- 12224687
TI  - The link between Helicobacter pylori infection and rosacea.
AB  - BACKGROUND: Rosacea is a common condition of unknown aetiology that is usually
      accompanied by gastrointestinal symptoms and responds favourably to treatment
      with antibiotics. AIMS/METHODS: This study was designed to examine the prevalence
      of gastric Helicobacter pylori (Hp) infection verified by 13C-UBT, CLO-test, Hp
      culture and serology (IgG and IgA) and the presence of Hp in the oral cavity
      evidenced by CLO-test, Hp culture and saliva anti-Hp antibodies (IgG and IgA).
      During gastroduodenoscopy antral and fundic biopsy samples were taken for
      histological evaluation (the Sydney system). This study was performed on 60
      subjects 30-70 years old with visible cutaneous rosacea symptoms and 60 age- and
      gender-matched controls without skin diseases but with dyspeptic symptoms similar
      to those of rosacea and without endoscopic changes in gastroduodenal mucosa (non
      ulcer dyspepsia--NUD). RESULTS: The Hp prevalence in rosacea patients was about
      88%, compared to 65% in the NUD controls. A noticeable number of rosacea patients
      showed chronic active gastritis predominantly in antrum but also in the corpus
      while those with NUD showed only mild gastritis confined to the antrum only.
      Following the initial examination, a typical 1 week systemic anti-Hp therapy,
      induding omeprazole (2 x 30 mg), clarithromycin (2 x 500 mg) and metronidazole (2
      x 500 mg), plus gargling and application of metronidazole paste in the case of Hp
      oral cavity infection. After the application of the systemic and local therapy in
      the oral cavity, Hp was eradicated from the stomach in 97% and from the oral
      cavity in 73% of treated patients. Within 2-4 weeks, the symptoms of rosacea
      disappeared or decreased markedly in 51 subjects. SUMMARY: We conclude that: (1)
      rosacea is a disorder with various gastrointestinal symptoms closely related to
      gastritis, especially involving the antrum mucosa; (2) the eradication of Hp
      leads to improvement of symptoms of rosacea and reduction in related
      gastrointestinal symptoms; (3) the lack of improvement of cutaneous symptoms in
      rosacea after eradication of Hp from the gastric mucosa could depend on bacteria
      in the oral cavity; and (4) rosacea could be considered as one of the
      extragastric symptoms of Hp infection probably mediated by Hp-related cytotoxins
      and cytokines.

PMID- 12224688
TI  - Inpatient dermatology: characteristics of patients and admissions in a Spanish
      hospital.
AB  - BACKGROUND: Inpatient dermatology has not been properly described in many
      countries. National differences might be important in the evaluation of its
      usefulness and the applicability of politics of health expenditure restrictions.
      OBJECTIVE: To describe inpatient activity and readmission rates in a dermatology
      department in Spain. STUDY DESIGN: Cross-sectional prospective study in a single
      hospital. SETTING: Secondary care hospital of the National Health Service in
      Pontevedra (Spain). METHODS: From May 1997 to December 2000, all discharge sheets
      (1048) were included in the study, codified and described. RESULTS: Surgery was
      the reason for admission in 37% of the inpatients. The most frequent diagnosis
      were: neoplasm (36%), infection (15%), psoriasis (10%), other (10%), dermatitis
      (6%) and drug reaction (5%). Readmission rates were 1.8% within 30 days, and
      12.5% within 1 year. CONCLUSIONS: Inpatient dermatology is different in different
      countries. Compared with what has been described in the USA or UK, our data
      suggest an important surgical content of inpatient dermatology in Spain, not
      reported in those countries. Medical diagnoses also differ, consisting of more
      infections, and less psoriasis and dermatitis in our setting. Readmission rates
      are low when compared with previously published ones, a finding that supports a
      long-term benefit of hospitalization.

PMID- 12224689
TI  - Pre-operative diagnosis of pigmented skin lesions: in vivo dermoscopy performs
      better than dermoscopy on photographic images.
AB  - BACKGROUND: Epiluminescence microscopy (ELM) (dermoscopy, dermatoscopy) is a
      technique for non-invasive diagnosis of pigmented skin lesions that improves the
      diagnostic performance of dermatologists. Little is known about the possible
      influence of associated clinical features on the reliability of dermoscopic
      diagnosis during in vivo examination. OBJECTIVE: To compare diagnostic
      performance of in vivo dermoscopy (combined clinical and dermoscopic examination)
      with that of dermoscopy performed on photographic slides (pure dermoscopy).
      DESIGN: This case series comprised 256 pigmented skin lesions consecutively
      identified as suspicious or equivocal during examination in a general
      dermatological clinic. Clinical examination and in vivo dermoscopy were performed
      before excision by two trained dermatologists. The same observers carried out
      dermoscopy on photographic slides at a later time, and these three diagnostic
      classifications were reviewed together with the histological findings for the
      individual lesions. This was carried out in a university hospital. RESULTS: In
      vivo dermoscopy performed better than dermoscopy on photographic slides for
      classification of pigmented skin lesions compared with histological diagnosis,
      and both performed better than general clinical diagnosis. In vivo dermoscopic
      diagnosis of melanoma showed 98.1% sensitivity, 95.5% specificity and 96.1%
      diagnostic accuracy while dermoscopic diagnosis of melanoma on photographic
      slides was less reliable with 81.5% sensitivity, 86.7% specificity and 85.2%
      diagnostic accuracy. In particular, diagnosis of melanoma based on photographic
      slides led to nine false negative cases (three in situ, six invasive; thickness
      ranges 0.2-1.5 mm). CONCLUSIONS: In vivo dermoscopy, i.e. combined clinical and
      dermoscopic examination, is more reliable than dermoscopy on photographic slides.
      In clinical practice, therefore, in vivo dermoscopy cannot be considered
      independent from associated clinical characteristics of the lesions, which help
      the trained observer to reach a more precise classification. This may have
      implications on the reliability of ELM diagnosis made by an observer not fully
      trained in the clinical diagnosis of pigmented skin lesions or by a remote
      observer during digital ELM teleconsultation.

PMID- 12224690
TI  - Assessment of depression in subjects with psoriasis vulgaris and lichen planus.
AB  - AIM: The aim of this study was to investigate the frequency of depressive
      symptoms in psoriasis vulgaris and lichen planus and to evaluate the relationship
      between the Beck depression scores and the Psoriasis Area and Severity Index
      (PASI) scores of subjects with psoriasis vulgaris. SUBJECTS: The study involved
      120 subjects attending the dermatology clinic of Izmir Ataturk Training Hospital
      (Izmir, Turkey) and comprised 50 subjects with psoriasis vulgaris, 30 with lichen
      planus and 40 healthy control subjects. RESULTS: Subjects with psoriasis
      vulgaris, lichen planus and controls had depression scores of 58%, 53% and 20%,
      respectively. The Beck depression scores of patients with psoriasis vulgaris were
      significantly higher than those of the control group. The PASI scores showed a
      correlation with Beck depression scores. Smoking and drinking were very common in
      subjects with psoriasis vulgaris. There was no correlation between the duration
      of illness and depressive symptoms. CONCLUSIONS: This study confirms the
      importance of depressive symptoms in two common dermatological diseases. It is
      important to recognize this association as it affects both clinical outlook and
      response to treatment.

PMID- 12224691
TI  - Pemphigus vulgaris with oral involvement: evaluation of two different systemic
      corticosteroid therapeutic protocols.
AB  - BACKGROUND: Pemphigus vulgaris is a potentially life-threatening disease
      characterized by cutaneous and mucosal blistering. Systemic corticosteroids
      remain the mainstay of therapy, transforming an invariably fatal disease into one
      with a mortality that is now less than 10%. Nevertheless, oral lesions are often
      recalcitrant and corticosteroid therapy can provoke adverse effects. OBJECTIVE:
      To determine whether two different regimens of systemic corticosteroid therapy
      based on prednisone gave different benefits. METHOD: We examined two different
      regimens of systemic corticosteroid therapy based on prednisone in an open study.
      Ten patients (group A) were treated with systemic corticosteroids, in a
      therapeutic protocol made up of orally administered prednisone. Ten matched
      patients (group B) were treated with systemic corticosteroids alternating a pulse
      of intravenous betamethasone with orally administered prednisone. RESULTS AND
      CONCLUSIONS: The pulse protocol appeared to have some advantages both in a
      shorter time to resolution of symptoms and oral lesions, and in terms of minor
      adverse effects.

PMID- 12224692
TI  - Varicella zoster viraemia during herpes zoster is not associated with neoplasia.
AB  - BACKGROUND: Shingles are caused by an endogenous or exogenous reinfection with
      varicella zoster virus (VZV). Up to 50% of individuals with Hodgkin's disease
      develop herpes zoster; however, no association could be shown between the
      occurrence of herpes zoster and underlying subclinical malignancies. OBJECTIVE:
      This study was conducted to investigate whether VZV DNA could be detected by
      polymerase chain reaction (PCR) in the blood of herpes zoster patients and
      whether there was an association between VZV viraemia and previous or concurrent
      neoplasias. METHODS: At least five blood samples from 28 patients with herpes
      zoster were investigated by internally controlled PCR enzyme-linked immunosorbent
      assay prior to and during therapy with aciclovir. RESULTS: None of 13 patients,
      two with a history of neoplasia and two with a neoplasia at the time of the
      study, showed any signs of viraemia with VZV, and 14 patients had inconsistent
      viraemia, one with a history of neoplasia and two with neoplasia at the time of
      the study. In one patient VZV DNA was detected in the blood for 6 days. This
      patient died soon after from metastatic malignant melanoma. CONCLUSIONS: VZV
      viraemia may occur during herpes zoster episodes, even in patients without
      evidence of immunosuppression; however, this viraemia is, in most cases,
      inconsistent and does not provide any specific information concerning underlying
      unrecognized malignancies.

PMID- 12224693
TI  - Scleroderma 'en coup de sabre' and progressive facial hemiatrophy. Is it possible
      to differentiate them?
AB  - The aim was to be able to evaluate the diagnosis of two diseases by a consensus
      of clinical opinion used in the Department of Dermatology of the National
      Institute of Paediatrics in Mexico City. To differentiate between scleroderma 'en
      coup de sabre' (SCS) and progressive facial hemiatrophy (PFH), colour slides of
      13 patients diagnosed as SCS and nine as PFH were examined by two dermatologists
      and microscopic slides by two pathologists. In both cases, the slides were
      randomly presented and no clinical information was given. The clinical and
      histopathological findings were statistically compared with two-tailed tests and
      alpha = 0.05. Kappa coefficients were obtained to evaluate the concordance
      between dermatologists, pathologists, and in terms of the consensus diagnosis.
      The usefulness of photographic assessment is limited by the inability to palpate
      the consistency of lesions. The most important clinical feature that
      differentiated both conditions was cutaneous sclerosis present in eight of 13
      patients with SCS and in none of the PFH patients (P < 0.005). Other clinical
      features more frequently found in SCS were cutaneous hyperpigmentation and
      alopecia. The more frequent clinical features in PFH were total hemifacial
      involvement and ocular changes. Statistically significant histopathological
      features were: connective tissue fibrosis present in all cases with SCS and two
      of nine patients with PFH (P < 0.0002); adnexal atrophy present in 11 of 13
      patients with SCS, and in three of nine with PFH (P < 0.02), and mononuclear cell
      infiltrates in all patients with SCS cf. six with PFH (P < 0.05). Our results
      suggest that in most cases it is possible to differentiate SCS from PFH based on
      clinicopathological findings.

PMID- 12224694
TI  - The importance of accurate dosage of topical agents: a method of estimating
      involved area and application to calcipotriol treatment failures.
AB  - Little attention is given to accurate dosage of topical medication which is a
      potential source of side-effects and treatment failure. There are studies on the
      dosage for 'sparing' application relevant to topical steroids but not for
      'liberal' application. Though calcipotriol is a first line topical treatment for
      psoriasis, approximately one-third of patients do not respond adequately. The
      aims of the present study were to define liberal dosage, to develop a method of
      calculation of area of involved skin and to evaluate the efficacy of calcipotriol
      in optimized liberal dosages, based on preliminary studies, in calcipotriol
      treatment failures. Weight/unit area of ointment and cream base, constituting
      liberal application, was determined in six normal volunteers. The area of
      psoriatic involvement in 24 calcipotriol non-responders was estimated by a 'fill
      up' method and a modified 'hand' method. The results of the two methods were
      similar (Pearson correlation coefficient 0.68, P < 0.0001) but the 'hand' method
      proved easier in use and was the preferred method for the rest of the study. The
      patients applied calcipotriol at their accustomed rates for at least 2 weeks and
      then at the calculated liberal rates, using cream in the morning and ointment at
      night, for 4 weeks. The efficacy measures were Psoriasis Area and Severity Index
      (PASI) (primary measure), a four-point efficacy score and a visual analogue
      scale. As a result of the preliminary study and the actual amounts used by the
      patients in the psoriasis treatment study reported below, liberal application has
      been defined as 50 g/m2 per application for ointment base and 40 g/m2 per
      application for cream. At this dosage, an average individual would use
      approximately 100 g of medication/week to treat 10% of the body surface. During
      the 4-week treatment study, the psoriasis patients used an average of 39 g (SD 17
      g)/m2 per application of cream and 52 g (SD 13 g)/m2 per application of ointment.
      All efficacy measures showed marked improvement (P < 0.0001). The frequency
      distribution of the PASI reduction defined responsive (70% of patients) and
      poorly responsive groups (30%), with mean PASI reduction of 60% and 17%,
      respectively.

PMID- 12224695
TI  - Giant exophytic basal cell carcinoma treated with radiotherapy.
AB  - Basal cell carcinomas may attain giant proportions due primarily to recurrence or
      because the tumour is neglected. We report the case of a 66-year-old man who
      presented with a bleeding, polypoid, cutaneous tumour located on the left
      shoulder region of 13 years duration. The man had not received any previous
      treatment. The lesion was biopsied and histopathologically diagnosed as a solid
      type basal cell carcinoma with focal areas of squamous differentiation and
      keratinization. The man refused complete surgical removal and therefore was
      treated with roentgentherapy, with satisfactory results and no complications in
      the irradiated area. No recurrences had manifested after 1 year follow-up.

PMID- 12224696
TI  - Lipomatous melanocytic nevomatosis.
AB  - Giant congenital melanocytic nevi (GCMN) are rare and occur in about one out of
      every 200,000-500,000 births. Their importance resides in the aesthetic
      alteration they produce and in the possibility of malignant transformation or in
      their association with nevi in the central nervous system as a distinctive
      syndrome: neurocutaneous melanoblastosis or nevomatosis, due to the fact that
      nervous system lesions are produced by infiltration of nevus cells. We present
      here a patient with a combination of GCMN with an outstanding lipomatosis located
      on the same area.

PMID- 12224697
TI  - Pretibial myxedema as the initial manifestation of Graves' disease.
AB  - Pretibial myxedema (PM) is a localized thickening of the pretibial skin due to
      accumulation of acid mucopolysacharides (glycosaminoglycans). Its pathogenesis is
      still under investigation. Pretibial myxedema, exophthalmus and thyroid acropachy
      are the dassic extrathyroidal manifestations of Graves' disease. Almost
      invariably, PM follows the onset of ophthalmopathy, developing after the
      diagnosis and treatment of hyperthyroidism. Pretibial myxedema preceding Graves'
      ophthalmopathy is rare. We report the case of a 28-year-old Greek woman, who
      presented with multiple, asymptomatic nodules and plaques of the lower legs in
      the absence of other physical findings. Histopathologic examination revealed
      deposition of mucopolysacharides in the lower dermis. Laboratory investigation
      showed elevated serum T3 and T4 and depressed TSH levels. In our patient,
      pretibial myxedema was the earliest manifestation, leading to the diagnosis of
      Graves' disease.

PMID- 12224698
TI  - A case of giant congenital nevocytic nevus with neurotization and onset of
      vitiligo.
AB  - The authors report the case of a 21-year-old woman with a giant congenital
      nevocytic nevus (GCNN) who developed vitiligo at the age of 16 years on skin
      areas remote from the GCNN. This is the first reported case of GCNN developing
      neurotization combined with vitiliginous changes within the GCNN lesion.
      Treatment with PUVA achieved repigmentation of the vitiligo lesions, except for
      the hypochromic areas within the area of the nevus that were shielded from UVA
      radiation.

PMID- 12224699
TI  - Elastosis perforans serpiginosa in an adult with Down's syndrome: report of a
      case with symmetrical localized involvement.
AB  - Elastosis perforans serpiginosa (EPS) is a rare perforating dermatosis in which
      elastic fibers extrude from the papillary dermis producing umbilicated papules,
      characteristically arranged to form arciform or serpiginous patterns on the skin.
      It can be observed in patients with Down's syndrome, in whom in some cases the
      disease has been reported to be more widespread and to run a longer course. We
      present the case of a 20-year-old girl with Down's syndrome, hypothyroidism, acne
      and hypertrichosis, who had a 2-year history of multiple atrophic lesions with an
      arciform pattern on the distal extensor portions of both thighs, histologically
      showing the typical features of EPS.

PMID- 12224700
TI  - Malignant fibrous histiocytoma arising on chronic osteomyelitis.
AB  - We present a case of a primary malignant fibrous histiocytoma of the skin (MFH)
      arising on chronic osteomyelitis in a 67-year-old woman. Although this condition
      seems to be a predisposing factor for the onset of the malignancy, MFH
      complicating chronic osteomyelitis is generally localized at the level of the
      bone tissue. In the case we report the neoplasm was primitively localized at the
      dermal and subcutaneous level and presented as a rapidly growing mass.

PMID- 12224701
TI  - Mycosis fungoides presenting as Ofuji's papuloerythroderma.
AB  - We report three patients presented with clinical features of Ofuji's
      papuloerythroderma (pruritic erythematous papules and extensive erythema sparing
      all skin folds), however, showing histopathological findings of mycosis fungoides
      (Pautrier's microabscess, haloed lymphocytes, disproportionate epidermotropism,
      and wiry collagen bundles). One case was associated with plaque stage of mycosis
      fungoides and follicular mucinosis. T-cell receptor (TCR) gene rearrangement
      analysis in the lesional skin tissue demonstrated rearrangement of the gamma
      chain in all cases. HTLV-1 serology was negative for two patients who conducted
      HTLV-1 test. We think that Ofuji's papuloerythroderma might be a variant of early
      mycosis fungoides rather than secondary skin manifestations to certain cutaneous
      inflammatory diseases.

PMID- 12224702
TI  - Keratosis pilaris atrophicans in mother and daughter.
AB  - We report two cases of keratosis follicularis spinulosa decalvans in a Caucasian
      family involving a 28-year-old woman and her mother. This is an unusual family in
      that no male relatives are similarly affected. Secondly, both patients have no
      significant eye changes but quite extensive scarring alopecia. To the best of our
      knowledge this is the second reported family in the UK.

PMID- 12224703
TI  - Mycosis fungoides presenting with extensive pyoderma gangrenosum-like ulcers.
AB  - Mycosis fungoides (MF) may present with atypical clinical manifestations. Usually
      it mimics various chronic dermatoses, with the appearance of ulcers during the
      tumour stage. Infrequently, cutaneous ulcers are the main or initial sign of
      lymphoma. We report the case of a man who presented multiple skin lesions that
      clinically appeared to be pyoderma gangrenosum (PG). However, histological and
      immunohistochemical examination revealed MF. This case illustrates that PG-like
      ulcers maybe atypical cutaneous manifestations of MF and exceptionally the
      presenting sign of this disease.

PMID- 12224704
TI  - Development of oesophageal involvement in a subject with pemphigus vulgaris: a
      case report and review of the literature.
AB  - We present the case of a 50-year-old-man with pemphigus vulgaris involving the
      oropharyngolaryngeal mucosa and oesophagus. Oesophageal involvement of pemphigus
      vulgaris is relatively uncommon, especially in subjects in clinical remission,
      and has been rarely described in the literature. Endoscopic examination should be
      performed to avoid inappropriate therapy due to misdiagnosis of steroid-induced
      oesophagitis and peptic ulcers.

PMID- 12224705
TI  - Pseudoverrucous papules: an aspect of incontinence in children.
AB  - Pseudoverrucous papules and nodules can be observed on skin surrounding
      urostomies and colostomies. These lesions appear to be uncommon, and sometimes
      can be misdiagnosed, even leading to surgical removal. We report the case of a 12
      year-old boy whose lesions appeared in crops in an area subjected to urine
      leakage and spontaneously regressed in time. In this patient, anogenital warts
      had to be ruled out, but many skin diseases must be considered in the
      differential diagnosis of these misunderstood lesions. We stress the importance
      of a skin examination by a trained professional aware of these problems to avoid
      unnecessary investigations and treatments.

PMID- 12224706
TI  - Pulmonary tuberculosis with cutaneous aspects of sarcoidosis.

PMID- 12224707
TI  - Multiple linear lichen planus in HIV patient.

PMID- 12224708
TI  - Topotecan-induced celluitis-like fixed drug eruption.

PMID- 12224709
TI  - Ineffectiveness of imiquimod therapy for Alopecia Totalis/Universalis.

PMID- 12224710
TI  - Cyclosporin A and alopecia areata.

PMID- 12224711
TI  - Turn-over lining flaps to repair full-thickness alar defects.

PMID- 12224712
TI  - Generalized granuloma annulare associated with Plummer's disease.

PMID- 12224713
TI  - In vivo anti-inflammatory effects of fexofenadine in chronic idiopathic
      urticaria.

PMID- 12224714
TI  - Multiple minute digitate hyperkeratosis.

PMID- 12224715
TI  - Relaxing incision in cutaneous facial surgery in elderly subjects.

PMID- 12224716
TI  - Prurigo gestationis.

PMID- 12224717
TI  - Coexistence of psoriasis vulgaris, bullous pemphigoid and vitiligo: a case
      report.

PMID- 12224718
TI  - Cardiology's 10 greatest discoveries of the 20th century.
AB  - We present a brief summary of the 10 greatest cardiologic developments and
      discoveries of the 20th century Described are electrocardiography; preventive
      cardiology and the Framingham Study; "lipid hypotheses" and atherosclerosis;
      coronary care units; echocardiography; thrombolytic therapy; cardiac
      catheterization and coronary angiography; open-heart surgery; automatic
      implantable cardiac defibrillators; and coronary angioplasty. These topics are
      the personal choices of the authors.

PMID- 12224719
TI  - Predictive value of conventional computed tomography in determining proximal
      extent of abdominal aortic aneurysms and possibility of infrarenal clamping.
AB  - The present study aimed to evaluate the diagnostic reliability of computed
      tomography in determining the proximal extent of abdominal aortic aneurysms and
      the possibility of infrarenal clamping. Preoperative computed tomographic
      findings, together with the operative data for 95 patients, were retrospectively
      analyzed in light of the operative findings. Eighty-nine (93.68%) of the patients
      were men and 6 (6.32%) were women, with a mean age of 66.27 +/- 18.14 years.
      Diagnosis of infrarenal aneurysm by computed tomography was confirmed at the time
      of surgery in 91 (95.79%) of 95patients. The negative-predictive value of
      computed tomography in detecting supra-aneurysmal renal arteries was found to be
      95.79%. The specificity was 98.91%. Infrarenal cross-clamping was performed in 59
      (62.11%) of 95 patients, whose aortic segments between the renal artery orifices
      and the proximal borders of the aneurysms had a mean length of 26.4 +/- 7.11 mm
      by computed tomography Suprarenal clamping was required in 36 (37.89%) of the 95
      patients, whose aortic segments had a mean length of 12.7 +/- 3.48 mm. We
      conclude that conventional computed tomography is reasonably accurate in
      determining the proximal extent of abdominal aortic aneurysms. Although there is
      a high rate of error in determining the possibility of infrarenal clamping when
      no specific measurements are taken, infrarenal clamping can be planned when
      measurement by computed tomography shows a length of > or = 26 mm between the
      renal arteries and the proximal extent of the aneurysm. In patients with shorter
      aortic segments, suprarenal aortic clamping should be considered.

PMID- 12224720
TI  - Magnetic resonance imaging of myocardial fibrosis in hypertrophic cardiomyopathy.
AB  - Myocardial fibrosis can occur in patients who have hypertrophic cardiomyopathy in
      the absence of epicardial coronary disease. In such patients, myocardial fibrosis
      has been linked to a poorer prognosis than in those without fibrosis. Gadolinium
      DTPA delayed-enhancement magnetic resonance imaging (de-MRI) accurately
      identifies regions of myocardial fibrosis. We used de-MRI to screen for
      myocardial fibrosis in 8 patients with nonobstructive hypertrophic cardiomyopathy
      that had been diagnosed by 2-dimensional echocardiography. After localization of
      the heart and acquisition of electrocardiographically gated cine images,
      gadolinium-DTPA (0.2 mmol/kg) was administered to the patient. Fifteen minutes
      later, de-MRI images were obtained using a T1-weighted, inversion-recovery fast,
      low-angle shot sequence. Images were gated to end-diastole and obtained during a
      single breath-hold. The inversion time was modified iteratively to obtain maximal
      nulling of the signal from the ventricular myocardium. Regions of myocardium with
      abnormally high signals (>300% of remote normal myocardium) were designated as
      fibrotic. Eight patients with hypertrophic cardiomyopathy underwent de-MRI. The
      mean age was 52 years, the mean left ventricular mass was 201 grams, and the mean
      ejection fraction was 0.68. In the 6 patients with recent clinical deterioration,
      de-MRI showed clearly delineated areas of myocardial fibrosis; no such areas were
      seen in the 2 asymptomatic patients. We conclude that patients with symptomatic
      hypertrophic cardiomyopathy display regions of abnormal signal intensity on de
      MRI that likely represent fibrosis. This technique may provide useful information
      in the evaluation of such patients and warrants further study.

PMID- 12224721
TI  - W. Proctor Harvey: a master clinician-teacher's influence on the history of
      cardiovascular medicine.
AB  - Medicine has become driven by research and technology, both of which have yielded
      indisputable benefits. Yet we are now so dependent upon such advancements that
      many practitioners have lost the basic clinical skills that enable bedside
      diagnosis. In the 2nd half of the 20th century, W. Proctor Harvey helped to keep
      alive the classic art of medicine.

PMID- 12224722
TI  - Pituitary apoplexy presenting as Addisonian crisis after coronary artery bypass
      grafting.
AB  - Addisonian crisis, also commonly referred to as adrenal crisis, occurs when the
      cortisol produced by the adrenal glands is insufficient to meet the body's acute
      needs. The symptoms are nonspecific and can mimic other processes, such as
      sepsis. Hypotension, lethargy, and fever can all be presenting signs. Secondary
      addisonian crisis can also result from pituitary apoplexy. Pituitary apoplexy
      usually occurs as hemorrhagic or ischemic necrosis in the presence of a pre
      existing pituitary adenoma, and is a rare sequela of surgery. The symptoms of
      pituitary apoplexy are typically impressive and are relieved by urgent
      transsphenoidal decompression. Hypopituitarism resulting from pituitary apoplexy
      can be treated with exogenous hormones. The case presented herein illustrates
      occult pituitary apoplexy that occurred after on-pump coronary artery bypass
      grafting. In this patient, the initial signs of addisonian crisis were
      overlooked; however, once recognized, they were reduced dramatically with
      standard stress-dose cortisone. A suprasellar mass with a cystic component was
      found on magnetic resonance imaging. The hemorrhagic pituitary gland was treated
      by transsphenoidal decompression, which relieved the patient's bitemporal
      hemianopia and 6th-nerve palsy.

PMID- 12224723
TI  - Sinus node dysfunction associated with lithium therapy in a child.
AB  - Lithium salts have been used extensively in both adults and children during the
      last 30 years, for the treatment of a variety of psychiatric conditions,
      including bipolar disorder The cardiac side effects of lithium in adult patients
      have been well described. However, to the best of our knowledge, there are no
      reports of lithium-induced cardiac side effects in pediatric patients. We
      describe the case of a 9-year-old boy who developed cardiac toxicity while
      receiving long-term lithium therapy.

PMID- 12224724
TI  - Lung hernia as a sequela to limited-access mitral valve surgery.
AB  - We report a case of a 36-year-old man who developed a lung hernia after a
      minimally invasive mitral valve repair. Lung hernias are uncommon. Most are
      acquired and may be classified as traumatic, spontaneous, pathologic, or
      postoperative. In theory, minimal-access surgical techniques should decrease the
      likelihood of herniation, in comparison with open thoracotomy. Our review of the
      literature revealed only 2 reports of this sequela in association with this
      surgical procedure. Repair was performed due to persistent symptoms, including
      pleurisy and dyspnea, and interference with the patient's daily activities.
      Surgical repair led to complete resolution of these problems.

PMID- 12224725
TI  - Complete congenital sternal cleft associated with pectus excavatum.
AB  - We report herein a rare case of complete congenital sternal cleft (absent
      sternum) and anterior pericardial defect in association with pectus excavatum. In
      neonates with absent sternum, the sternal bars can be easily approximated by
      simple suture, due to the flexibility of the cartilaginous thorax. There is also
      little danger of cardiac compression when the repair is performed early in life.
      If reconstruction is delayed, the increased rigidity of the chest wall and the
      physiologic accommodation of the thoracic organs to the circumference of the
      chest render simple approximation impossible, without serious compromise of the
      heart and lungs. Our patient was a 13-year-old girl, whose case was particularly
      unusual because of the association of sternal cleft with pectus excavatum. After
      surgical correction of the pectus excavatum, we were able to construct a sternum
      by incising the lateral border of each sternal bar, thereby creating flaps that
      we sutured together at midline. The sternal bars were then approximated by loops
      of nonabsorbable suture around their circumference. The patient had an
      uncomplicated course, and at the 12-month follow-up visit, her sternal appearance
      was normal.

PMID- 12224726
TI  - Aortic thrombus after coil occlusion of a type E patent ductus arteriosus.
AB  - A 5-year-old girl was referred to our institution for closure of a silent patent
      ductus arteriosus. Cardiac catheterization revealed a tiny-to-small patent ductus
      arteriosus of the elongated, conical type (Type E). Coil occlusion was performed
      with a Gianturco coil, 0.035-4 cm(-3) mm. A follow-up echocardiogram showed a
      very small residual ductal shunt and a moderate-sized thrombus at the aortic end
      of the ductus arteriosus. The patient remained asymptomatic.

PMID- 12224727
TI  - Nontransplant cardiac surgery as a bridge to heart transplantation in pediatric
      dilated cardiomyopathy.
AB  - Partial left ventriculectomy and mitral valve repair, alone or in combination,
      have been used successfully to treat adult patients with end-stage dilated
      cardiomyopathy, yet the clinical results of this procedure in small children have
      been described only rarely. We report 2 cases of nontransplant cardiac surgery in
      small children with end-stage dilated cardiomyopathy The 1st patient received
      both a partial left ventriculectomy and mitral valve repair; the 2nd received
      only mitral valve repair. Subsequently, both underwent successful heart
      transplantation. We believe that nontransplant cardiac surgery can improve
      clinical status and act as a biological bridge, instead of a mechanical bridge,
      to heart transplantation in small children with end-stage dilated cardiomyopathy.

PMID- 12224728
TI  - Endoluminal stenting of the aorta as treatment of aortoesophageal fistula due to
      primary aortic disease.
AB  - A 78-year-old woman with severe chronic obstructive pulmonary disease was
      admitted to the emergency room with hematemesis. With use of esophagoscopy, chest
      computed tomographic scanning, and aortography, we found a large descending
      aortic aneurysm and a penetrating ulcer of the proximal descending aorta. We
      determined that the patient had an aortoesophageal fistula and pseudoaneurysm
      that had originated from a ruptured penetrating ulcer of the mid-descending
      aorta. We deployed two 100-mm stent grafts to seal the ruptured thoracic aorta.
      Six months later, the pseudoaneurysm was almost completely resolved, with no
      infection or endoleak. We advocate the use of endoluminal aortic stenting for
      aortoesophageal fistulas of aortic origin, particularly in patients with severe
      concomitant disease.

PMID- 12224729
TI  - Images in cardiovascular medicine. Superior vena cava syndrome with endovascular
      stenting.

PMID- 12224730
TI  - Images in cardiovascular medicine. Postoperative left ventricular pseudoaneurysm.

PMID- 12224731
TI  - Images in cardiovascular medicine. Right-sided double aortic arch in tetralogy of
      fallot.

PMID- 12224732
TI  - Images in cardiovascular medicine. Rheumatic stenosis of all four valves.

PMID- 12224733
TI  - Images in cardiovascular medicine. Multiple cardiac hydatid cysts: consistency of
      echocardiographic and surgical findings.

PMID- 12224734
TI  - Early clinical application of assisted circulation.

PMID- 12224735
TI  - Secondary cross-clamping and blood cardioplegia for refractory ventricular
      fibrillation after aortic cross-clamp removal.

PMID- 12224736
TI  - Transaortic double valve replacement.

PMID- 12224737
TI  - Anomalous origin of the right coronary artery from the left coronary sinus.

PMID- 12224738
TI  - Another indication for chest tube after pneumonectomy.

PMID- 12224739
TI  - Risk analysis and risk management in an uncertain world.
AB  - The tragic attacks of September 11 and the bioterrorist threats with respect to
      anthrax that followed have raised a set of issues regarding how we deal with
      events where there is considerable ambiguity and uncertainty about the likelihood
      of their occurrence and their potential consequences. This paper discusses how
      one can link the tools of risk assessment and our knowledge of risk perception to
      develop risk management options for dealing with extreme events. In particular,
      it suggests ways that the members of the Society for Risk Analysis can apply
      their expertise and talent to the risks associated with terrorism and discusses
      the changing roles of the public and private sectors in dealing with extreme
      events.

PMID- 12224740
TI  - Are received risk perception models alive and well?
AB  - Two recent papers on risk perception models are discussed. In these papers,
      quantitative analyses are presented of risk perception in relation to risk
      characteristics as specified in the Psychometric Model, and to cultural biases
      according to Cultural Theory. This comment points out that the data quality of
      these two studies is doubtful, with a very small convenience sample and a very
      low response rate. More importantly, the analyses show the same low levels of
      explained variance of risk perception as other researchers have found previously,
      but the authors still draw optimistic conclusions from their data. Such
      conclusions are unjustified.

PMID- 12224741
TI  - The role of risk analysis in understanding bioterrorism.
AB  - Recent events have made the domestic risk from bioterrorism more tangible. The
      risk management process so far, however, has not benefited from many of the
      contributions that analysts, communicators, and managers can make to the public
      discourse. Risk professionals can contribute much to the understanding of and
      solutions to bioterrorist events and threats. This article will provide an
      overview of the bioterrorism problem and outline a number of areas to which
      members of the Society for Risk Analysis, and other risk practitioners, could
      usefully contribute.

PMID- 12224742
TI  - What to do at low doses: a bounding approach for economic analysis.
AB  - To quantify the health benefits of environmental policies, economists generally
      require estimates of the reduced probability of illness or death. For policies
      that reduce exposure to carcinogenic substances, these estimates traditionally
      have been obtained through the linear extrapolation of experimental dose-response
      data to low-exposure scenarios as described in the U.S. Environmental Protection
      Agency's Guidelines for Carcinogen Risk Assessment (1986). In response to
      evolving scientific knowledge, EPA proposed revisions to the guidelines in 1996.
      Under the proposed revisions, dose-response relationships would not be estimated
      for carcinogens thought to exhibit nonlinear modes of action. Such a change in
      cancer-risk assessment methods and outputs will likely have serious consequences
      for how benefit-cost analyses of policies aimed at reducing cancer risks are
      conducted. Any tendency for reduced quantification of effects in environmental
      risk assessments, such as those contemplated in the revisions to EPA's cancer
      risk assessment guidelines, impedes the ability of economic analysts to respond
      to increasing calls for benefit-cost analysis. This article examines the
      implications for benefit-cost analysis of carcinogenic exposures of the proposed
      changes to the 1986 Guidelines and proposes an approach for bounding dose
      response relationships when no biologically based models are available. In spite
      of the more limited quantitative information provided in a carcinogen risk
      assessment under the proposed revisions to the guidelines, we argue that
      reasonable bounds on dose-response relationships can be estimated for low-level
      exposures to nonlinear carcinogens. This approach yields estimates of reduced
      illness for use in a benefit-cost analysis while incorporating evidence of
      nonlinearities in the dose-response relationship. As an illustration, the
      bounding approach is applied to the case of chloroform exposure.

PMID- 12224743
TI  - An exposure assessment for methylmercury from seafood for consumers in the United
      States.
AB  - An exposure model was developed to relate seafood consumption to levels of
      methylmercury (reported as mercury) in blood and hair in the U.S. population, and
      two subpopulations defined as children aged 2-5 and women aged 18-45. Seafood
      consumption was initially modeled using short-term (three-day) U.S.-consumption
      surveys that recorded the amount of fish eaten per meal. Since longer exposure
      periods include more eaters with a lower daily mean intake, the consumption
      distribution was adjusted by broadening the distribution to include more eaters
      and reducing the distribution mean to keep total population intake constant. The
      estimate for the total number of eaters was based on long-term purchase diaries.
      Levels of mercury in canned tuna, swordfish, and shark were based on FDA survey
      data. The distribution of mercury levels in other species was based on reported
      mean levels, with the frequency of consumption of each species based on market
      share. The shape distribution for the given mean was based on the range of
      variation encountered among shark, tuna, and swordfish. These distributions were
      integrated with a simulation that estimated average daily intake over a 360-day
      period, with 10,000 simulated individuals and 1,000 uncertainty iterations. The
      results of this simulation were then used as an input to a second simulation that
      modeled levels of mercury in blood and hair. The relationship between dietary
      intake and blood mercury in a population was modeled from data obtained from a 90
      day study with controlled seafood intake. The relationship between blood and hair
      mercury in a population was modeled from data obtained from several sources. The
      biomarker simulation employed 2,000 simulated individuals and 1,000 uncertainty
      iterations. These results were then compared to the recent National Health and
      Nutrition Examination Survey (NHANES) that tabulated blood and hair mercury
      levels in a cross-section of the U.S. population. The output of the model and
      NHANES results were similar for both children and adult women, with predicted
      mercury biomarker concentrations within a factor of two or less of NHANES
      biomarker results. However, the model tended to underpredict blood levels for
      women and overpredict blood and hair levels for children.

PMID- 12224744
TI  - The media and genetically modified foods: evidence in support of social
      amplification of risk.
AB  - Empirical examinations of the "social amplification of risk" framework are rare,
      partly because of the difficulties in predicting when conditions likely to result
      in amplification effects will occur. This means that it is difficult to examine
      changes in risk perception that are contemporaneous with increases and/or
      decreases in social or media discussion of the risks associated with a particular
      risk event. However, the collection of attitude data before, during, and after
      the increased reporting of the risks of genetically modified food in the United
      Kingdom (spring 1999) has demonstrated that people's risk perceptions do increase
      and decrease in line with what might be expected upon examination of the
      amplification and attenuation mechanisms integral to the framework. Perceptions
      of benefit, however, appeared to be permanently depressed by negative reporting
      about genetically modified food. Trust in regulatory institutions with
      responsibility for protecting the public was not affected. It was concluded that
      the social amplification of risk framework is a useful framework for beginning to
      explain the potential impact on risk perceptions of a risk event, particularly if
      that risk event is presented to the public as a new hazard occurring in a crisis
      context.

PMID- 12224745
TI  - What number is "fifty-fifty"?: redistributing excessive 50% responses in elicited
      probabilities.
AB  - Studies using open-ended response modes to elicit probabilistic beliefs have
      sometimes found an elevated frequency (or blip) at 50 in their response
      distributions. Our previous research suggests that this is caused by intrusion of
      the phrase "fifty-fifty," which represents epistemic uncertainty, rather than a
      true numeric probability of 50%. Such inappropriate responses pose a problem for
      decision analysts and others relying on probabilistic judgments. Using an
      explicit numeric probability scale (ranging from 0-100%) reduces thinking about
      uncertain events in verbal terms like "fifty-fifty," and, with it, exaggerated
      use of the 50 response. Here, we present two procedures for adjusting response
      distributions for data already collected with open-ended response modes and hence
      vulnerable to an exaggerated presence of 50%. Each procedure infers the
      prevalence of 50s had a numeric probability scale been used, then redistributes
      the excess. The two procedures are validated on some of our own existing data and
      then applied to judgments elicited from experts in groundwater pollution and
      bioremediation.

PMID- 12224746
TI  - Gender and race in beliefs about outdoor air pollution.
AB  - Universal need for, or reactions to, risk communications should not be assumed;
      potential differences across demographic groups in environmental risk beliefs,
      attitudes, and behaviors could affect risk levels or opportunities for risk
      reduction. This article reports relevant findings from a survey experiment
      involving 1,100 potential jurors in Philadelphia concerning public responses to
      outdoor air pollution and air quality information. Flynn et al. (1994) and
      Finucane et al. (2000) found significant differences in risk ratings for multiple
      hazards, and in generic risk beliefs, between white men (or a subset) and all
      others (white women, nonwhite men, and nonwhite women). This study examined
      whether white men had significantly different responses to air pollution and air
      pollution information. An opportunity sample of volunteers from those awaiting
      potential jury duty in city courts (matching census estimates for white versus
      nonwhite proportions, but more female than the city's adult population and more
      likely to have children) filled out questionnaires distributed quasi-randomly. On
      most measures there were no statistically significant differences among white men
      (N = 192), white women (N = 269), nonwhite men (N = 165), and nonwhite women (N =
      272). Nonwhites overall (particularly women) reported more concern about and
      sensitivity to air pollution than whites, and were more concerned by (even overly
      sensitive to) air pollution information provided as part of the experiment.
      Nonwhites also were more likely (within-gender comparisons) to report being
      active outdoors for at least four hours a day, a measure of potential exposure to
      air pollution, and to report intentions to reduce such outdoor activity after
      reading air pollution information. Differences between men and women were less
      frequent than between whites and nonwhites; the most distinctive group was
      nonwhite women, followed by white men. Flynn et al. (1994) and Finucane et al.
      (2000) found a far larger proportion of significant differences, with white men
      as most distinctive, probably due to use of different measures, study design, and
      population samples. However, all three studies broadly confirm the existence of
      gender and race interactions in risk beliefs and attitudes (particularly for
      white men and nonwhite women) that deserve more attention from researchers.

PMID- 12224747
TI  - The quality of stakeholder-based decisions.
AB  - The increased use of stakeholder processes in environmental decision making has
      raised concerns about the quality of decisions these processes produce. Some
      claim that stakeholders make inadequate use of scientific information and
      analysis and are all too ready to sacrifice technical quality for political
      expediency. This article looks to the case study record to examine the quality of
      the decisions from stakeholder-based processes. The data for the analysis come
      from a "case survey," in which researchers coded information from 239 published
      case studies of stakeholder involvement in environmental decision making. These
      cases reflect a diversity of planning, management, and implementation activities
      carried out by environmental and natural resource agencies at many levels of
      government. Overall, the case-study record suggests that there should be little
      concern that stakeholder processes are resulting in low-quality decisions. The
      majority of cases contain evidence of stakeholders improving decisions over the
      status quo; adding new information, ideas, and analysis; and having adequate
      access to technical and scientific resources. Indeed, data suggest that it is the
      more intensive stakeholder processes--precisely those that have aroused recent
      concern--that are more likely to result in higher-quality decisions.

PMID- 12224748
TI  - Risk perception and new age beliefs.
AB  - This is a study of risk perception in relation to New Age (NA) beliefs, including
      traditional folk superstition and belief in paranormal phenomena, as well as use
      of alternative healing practices. Data were also obtained on trust dimensions and
      on personality and psychopathology variables, as well as religious involvement.
      It was found that four factors accounted for the investigated NA beliefs, which
      were termed higher consciousness beliefs, denial of analytic knowledge,
      traditional superstition, and belief in the physical reality of the soul. NA
      beliefs were strongly and positively related to religious involvement, and
      negatively to educational level. These beliefs were also positively related to
      maladjustment and to concerns over tampering with nature. In regression analyses,
      it was found that NA beliefs explained about 15% of the variance of perceived
      risk, and that the most powerful explanatory factors were higher consciousness
      beliefs and beliefs in paranormal phenomena. Traditional superstition and use of
      healing practices did not contribute to explaining perceived risk.

PMID- 12224749
TI  - Priorities in information desire about unknown risks.
AB  - Research on risk perception aims to explain how people perceive risks in order to
      better communicate about them. Most of this research has tended to view people as
      passive risk perceivers. However, if confronted with an unknown risk, people can
      also actively seek information. The main purpose of this study was to investigate
      what kind of risk information people desire when confronted with an unknown risk
      and how this desire for information relates to the main dimensions underlying
      risk perception. Nine focus-group interviews were conducted. The main results of
      the focus groups were backed up by a paper-and-pencil questionnaire that was
      distributed among a random sample of 500 households in the Netherlands. Overall,
      people desire information with which they can determine the personal relevance of
      the risk confronting them. This pattern is similar to appraisal steps described
      by health behavior models. The focus-group results provide a dynamic picture of
      the way risk aspects might interact to create a final risk judgment.

PMID- 12224750
TI  - Stability and inoculation of risk comparisons' effects under conflict:
      replicating and extending the "asbestos jury" study by Slovic et al.
AB  - Promotion or criticism of risk comparisons in risk communication has far exceeded
      empirical tests of their effects. Slovic et al. (1990) experimented with a
      hypothetical jury trial in which an asbestos-installing firm was accused of
      subjecting school occupants to unreasonable risk. A risk comparison sharply
      reduced subjects' estimates of risk and judgments that the firm was guilty, but a
      critique of the risk comparison had risk estimates and guilt judgments rebounding
      to the original (without risk comparison) level. Slovic et al. concluded that
      risk comparisons' effects were highly unstable, at least in conflict-ridden
      situations such as a jury trial. The present study replicates and extends this
      important study, using the same stimuli and questions. The respective effects of
      the risk comparison and the critique recurred, although much less sharply than in
      Slovic et al. Moreover, judgments of guilt, risk, and other aspects of the case
      seemed shaped more by demographics and beliefs about risk generically (e.g.,
      about the likelihood of cancer after exposure to a carcinogen) than by either
      risk comparison or critique. A variant design, in which the defense's expert
      witness dismissed potential criticisms of the risk comparison, appeared to
      "inoculate" people against shifting their views after seeing the critique.
      Overall, these results show that risk comparisons might change some beliefs about
      risks in conflict and that "inoculation" can reduce vulnerability to criticism.
      However, the results also show strong limits on effects of both comparisons and
      their critiques: they shifted only a minority of judgments and had small effects
      relative to people's social locations and prior risk beliefs.

PMID- 12224751
TI  - Constructing scientific authorities: issue framing of chlorinated disinfection
      byproducts in public health.
AB  - The practice of chlorine disinfection of drinking water to reduce microbial risks
      provides substantial benefits to public health. However, increasing concern
      around potential risks of cancer associated with exposure to chlorinated
      disinfection byproducts confuses this issue. This article examines the science
      agenda regarding chlorinated disinfection byproducts (CDBP) and cancer in Canada
      and the United States, focusing on the social construction of scientific
      knowledge claims and evidence. Data for this analysis were obtained from
      published documents as well as from in-depth interviews with epidemiologists and
      toxicologists centrally involved with the issue in both countries. Results of the
      analysis suggest that toxicological scientists want to close the door on the
      "chloroform issue" due to increasing evidence that chloroform is safe at low
      doses, because epidemiological scientists can no longer move forward the cancer
      science until significant improvements can be made in assessing human exposures,
      and because the scientific foci of research on DBP have shifted accordingly.
      Further, a distinction emerges in terms of how scientific uncertainties are
      interpreted when they cross-cut disciplines in the context of human health risk
      assessment. We suggest this tension reflects a balance of how uncertainty and
      authorities are managed in a mandated science-policy domain. Sufficient evidence
      was provided to keep the DBP issue on the regulatory agenda and to generate
      additional research, yet authorities and concomitant interpretations of
      uncertainty were contested. Such science generation and contestation inevitably
      influences complex risk assessment processes with respect to what water-related
      health risks are addressed and how.

PMID- 12224752
TI  - Validating benefit and cost estimates: the case of airbag regulation.
AB  - Preregulation estimates of benefits and costs are rarely validated after
      regulations are implemented. This article performs such a validation for the
      mandatory automobile airbag requirement. We found that the original 1984 model
      used to estimate benefits became invalid when 1997 values were input into that
      1984 model. However, using a published 1997 cost-effectiveness model, we
      demonstrate, by replacing the model inputs with the values from 1984, that the
      1997 cost-effectiveness ratios, based on real-world crash data and tear-down cost
      data, are less attractive than what would have been originally anticipated. The
      three most important errors in the 1984 input values are identified: the
      overestimation of airbag effectiveness, the overestimation of baseline
      fatality/injury rates, and the underestimation of manual safety belt use. This
      case study, which suggests that airbags are a reasonable investment in safety,
      shows that the regulatory analysis tools do not always produce findings that are
      biased against health, safety, and environmental regulation. Future validation
      studies of health, safety, and environmental regulation should focus on
      validation of benefit and risk estimates, areas where we found significant error,
      as well as on cost estimates.

PMID- 12224753
TI  - Open issues from the 15th International Conference on Manganese.

PMID- 12224754
TI  - XANES spectroscopy: a promising tool for toxicology: a tutorial.
AB  - X-ray absorption near edge structure (XANES) spectroscopy can provide information
      on the oxidation state of metal ions within a biological sample and also the
      complexes in which it is found. This type of information could be of great use to
      toxicologists in understanding the mechanism of action of many toxic agents. The
      prospect of using a sophisticated physical technique such as XANES may be
      somewhat intimidating for those without a strong physical background. Here, we
      explain the concepts necessary to understand XANES spectroscopy at a level that
      can be easily understood by biological scientists without a strong physics
      background and describe useful sample preparation and data analysis techniques
      which can be adapted for a variety of applications. Examples are taken from an
      ongoing study of manganese in brain mitochondria and neuron-like cells.

PMID- 12224755
TI  - Mechanisms of manganese-induced rat pheochromocytoma (PC12) cell death and cell
      differentiation.
AB  - Mn is a neurotoxin that leads to a syndrome resembling Parkinson's disease after
      prolonged exposure to high concentrations. Our laboratory has been investigating
      the mechanism by which Mn induces neuronal cell death. To accomplish this, we
      have utilized rat pheochromocytoma (PC12) cells as a model since they possess
      much of the biochemical machinery associated with dopaminergic neurons. Mn, like
      nerve growth factor (NGF), can induce neuronal differentiation of PC12 cells but
      Mn-induced cell differentiation is dependent on its interaction with the cell
      surface integrin receptors and basement membrane proteins, vitronectin or
      fibronectin. Similar to NGF, Mn-induced neurite outgrowth is dependent on the
      phosphorylation and activation of the MAP kinases, ERK1 and 2 (p44/42). Unlike
      NGF, Mn is also cytotoxic having an IC50 value of approximately 600 microM.
      Although many apoptotic signals are turned on by Mn, cell death is caused
      ultimately by disruption of mitochondrial function leading to loss of ATP. RT-PCR
      and immunoblotting studies suggest that some uptake of Mn into PC12 cells depends
      on the divalent metal transporter 1 (DMT1). DMT1 exists in two isoforms resulting
      from alternate splicing of a single gene product with one of the two mRNA species
      containing an iron response element (IRE) motif downstream from the stop codon.
      The presence of the IRE provides a binding site for the iron response proteins
      (IRP1 and 2); binding of either of these proteins could stabilize DMT1 mRNA and
      would increase expression of the +IRE form of the transporter. Iron and Mn
      compete for transport into PC12 cells via DMT1, so removal of iron from the
      culture media enhances Mn toxicity. The two isoforms of DMT1 (+/-IRE) are
      distributed in different subcellular compartments with the -IRE species
      selectively present in the nucleus of neuronal and neuronal-like cells.

PMID- 12224756
TI  - Effects of manganese on oxidative stress in CATH.a cells.
AB  - The present study addressed the effects of Mn on oxidative stress in a
      catecholaminergic CATH.a cell line. Oxidative stress was measured with the
      fluorescent dye, 2',7'-dichlorofluoroscein (DCFH). In the diacetate form, the dye
      is taken up by the cells and cleaved by esterases, effectively trapping it within
      the intracellular space. DCFH is subsequently oxidized treatment in the presence
      of reactive oxygen species (ROS) to the fluorescent DCFH. The fluorescence was
      analyzed on an ACAS 470 Interactive Laser Cytometer. Treatment of CATH.a cells
      with MnCl2 (up to 10 mM) from 10 min up to 48 h was not associated with increased
      intracellular ROS formation. While manganese (Mn) treatment alone did not
      increase the rate of ROS formation, when short-term (10 min), Mn treatment was
      followed for the last 5 min with treatment with H2O2, Mn (at concentrations >5
      mM) significantly increased (P < 0.05) H2O2-induced ROS generation. Prolonged (24
      h) Mn treatment prior to exposure to H2O2 was associated with a statistically
      significant (P < 0.05) reduction in ROS generation compared with cells treated
      with H2O2 alone. This statistically significant decrease (P < 0.05) in ROS
      generation was preserved in CATH.a cells that were treated for 48 h with 10 and
      100 microM Mn followed by H2O2 exposure. Although the trend for diminished ROS
      generation was also apparent with 500 and 750 microM Mn (48 h), the decrease did
      not attain statistical significance. Combined these results suggest that Mn can
      act as both pro- and antioxidant, and that oxidative stress-related effects of Mn
      are dependent not only on the intracellular concentrations of the metal, but also
      the exposure duration, secondary oxidative challenges, and the overall oxidant
      "buffering" capacity of the cells.

PMID- 12224758
TI  - Effects of manganese (Mn) on the developing rat brain: oxidative-stress related
      endpoints.
AB  - We evaluated biochemical endpoints related to oxidative stress in brains of
      neonatal rats exposed to manganese (Mn). Oral Mn chloride (MnCl2) (0, 25, or 50
      mg Mn chloride kg(-1) body weight per day) was given daily to neonatal rats
      throughout lactation (i.e. from postnatal day (PND) 1 to 21). As previously
      reported by [J. Appl. Toxicol. 20 (2000) 179], this treatment paradigm results in
      increased cerebral cortex (CTX) Mn concentrations in PND 21 rats from both Mn
      treatment groups. High dose Mn exposure also results in increased cerebellar Mn
      concentrations. This preliminary study determined whether this exposure paradigm
      also affects cerebrocortical or cerebellar metallothionein (MT) mRNA levels,
      glutamine synthetase (GS) activity, GS protein levels, as well as total
      glutathione (GSH) levels. High dose Mn exposure significantly increased (P <
      0.05) total cerebrocortical GSH without accompanying changes in any of the other
      measured parameters. Therefore, it is unlikely that high dose Mn exposure is
      associated with oxidative stress in this experimental paradigm.

PMID- 12224759
TI  - The relationship of particle size to olfactory nerve uptake of a non-soluble form
      of manganese into brain.
AB  - The essential element, manganese, can produce chronic neuromotor impairment
      related to basal ganglia (BG) damage when it is presented in excessive
      quantities. The uptake and elimination patterns of manganese following ingestion
      have been well studied and, under normal conditions, excretion appears to keep
      manganese levels under tight control. Less is known about inhalation exposure,
      but it has been proposed that the lung might serve as a long-term reservoir for
      manganese transport into blood. Recent data suggest that a third route of
      exposure, transport by the olfactory nerve directly to the brain, might have
      importance in toxicology since such a route would bypass liver uptake and biliary
      excretion of manganese. In this study, we sought to determine how particle size
      and the use of a poorly soluble form of manganese might influence net systemic
      absorption of manganese dust and the potential role of the olfactory nerve in
      transport of manganese dioxide. Rats were exposed in nose-only exposure chambers
      to manganese dioxide (MnO2) aerosols of 1.3 and 18 microm mass median aerodynamic
      diameter (MMAD). The concentration of aerosols was kept constant at 3 mg/m3 as
      Mn. Following 15 days of exposure (five times per week for 3 weeks), rats were
      euthanized and tissues harvested for manganese determination carried out by
      graphite furnace atomic absorption spectroscopy. Small-particle MnO2 exposure
      resulted in an elevation in olfactory bulb manganese concentration, presumably
      through uptake by the olfactory nerve, but the effect was highly variable. While
      small increases in cortical and neostriatal manganese levels were also observed
      in these rats, they did not reach statistical significance. By contrast, there
      was no evidence of olfactory nerve MnO2 uptake in rats receiving the large
      particle exposure.

PMID- 12224757
TI  - The uptake of manganese in brain endothelial cultures.
AB  - The present study focused on central nervous system (CNS) transport kinetics of
      manganese phosphate and manganese sulfate; these findings were correlated with
      the transport kinetics of manganese chloride (MnCl2), a model Mn compound that
      has been previously studied. A series of studies was performed to address the
      transport of Mn salts in confluent cultured endothelial cells. The initial rate
      of uptake (5 min) of Mn salts (chloride, sulfate, and phosphate) in rat brain
      endothelial (RBE4) cell cultures is salt-dependent, with the highest rates of
      uptake for Mn chloride and Mn sulfate (as reflected by the greatest displacement
      of 54Mn compared with control). Mn phosphate had a lower rate of uptake than the
      other two Mn salts. These data show that brain endothelial cells efficiently
      transport Mn sulfate.

PMID- 12224760
TI  - Brain manganese concentrations in rats following manganese tetroxide inhalation
      are unaffected by dietary manganese intake.
AB  - Manganese-deficient individuals have decreased manganese elimination. This
      observation has prompted suggestions that relative manganese deficiency may
      increase the risk for manganese neurotoxicity following inhalation exposure. The
      objective of this study was to determine whether dietary manganese intake
      influences the pharmacokinetics of inhaled manganese tetroxide (Mn3O4). Postnatal
      day (PND) 10 rats were placed on either a low (2 ppm), sufficient (10 ppm), or
      high-normal (100 ppm) manganese diet for 2 months. Beginning on PND 77 +/- 2,
      male littermates were exposed 6 h per day for 14 consecutive days to 0, 0.042, or
      0.42 mg Mn3O4/m3. End-of-exposure tissue manganese concentrations and whole-body
      54Mn elimination rates were determined. Tissue manganese concentrations were
      dependent on the dietary intake of manganese, thus confirming that altered
      hepatic manganese disposition or metabolism occurred. Male rats given 100 ppm
      manganese diet developed increased manganese concentrations in the femur, liver,
      and bile and had elevated whole-body 54Mn clearance rates when compared to
      animals given 2 ppm manganese diet. Male rats exposed to 0.42 mg Mn3O4/m3 had
      increased manganese concentrations in the olfactory bulb, lung, liver, and bile
      when compared to air-exposed male rats. A significant interaction between the
      concentration of inhaled Mn3O4 and dietary manganese level was observed only with
      the end-of-exposure liver manganese concentration. Our results indicate that
      animals maintained on either a manganese-deficient or high manganese diet do not
      appear to be at increased risk for elevated brain manganese concentrations
      following inhalation exposure to high levels of Mn3O4.

PMID- 12224761
TI  - Effects of continuous low-dose exposure to organic and inorganic mercury during
      development on epileptogenicity in rats.
AB  - The effects of chronic, low-dose fetal and lactational organic (MeHgCl) and
      inorganic (HgCl2) mercury intoxication on epileptogenicity were investigated and
      compared in rats. The main observations after both mercury treatments were a
      facilitated seizure expression and propagation evoked by 4-aminopyridine (4-AP).
      The seizure susceptibility of the offspring seemed to be in a parallel relation
      to the mercury concentration in the cortical tissue, which was significantly
      higher in treated animals as compared to the controls. While MeHgCl enhanced the
      number of ictal periods, HgCl2 facilitated the duration of seizure discharges in
      younger animals. HgCl2 intoxication seemed to be more permanent than MeHgCl.
      Changes in the summated ictal activity--which is an indication of
      epileptogenicity--were observed in the opposite directions in the two treated
      groups with increasing age. The amplitudes of seizure discharges were smaller in
      both mercury-treated groups than in the controls, which could be a consequence of
      a depressed proliferation of neurons or enhanced cell death in the neocortex. In
      summary, we observed that adult rats exposed to organic or inorganic mercury
      chemicals during their embryonic life, are more prone to epilepsy than control
      rats given only 4-AP.

PMID- 12224762
TI  - Effects of oral cadmium exposure through puberty on plasma prolactin and
      gonadotropin levels and amino acid contents in various brain areas in pubertal
      male rats.
AB  - This work was undertaken to analyze if the effects of oral cadmium exposure
      through puberty, on plasma prolactin and gonadotropin levels are mediated by
      changes in amino acid contents in various brain areas in male rats. The contents
      of glutamate, glutamine, aspartate, GABA and taurine in the median eminence,
      anterior, mediobasal and posterior hypothalamus and prefrontal cortex in pubertal
      male rats exposed to 50 ppm of cadmium chloride (CdCl2) in the drinking waterfor
      1 month (through puberty) were measured by high performance liquid chromatography
      (HPLC). Plasma prolactin, LH and FSH levels were measured by specific RIA
      methodology. Plasma prolactin levels decreased after cadmium exposure, whereas
      plasma levels of LH and FSH were not changed by the metal administration. After
      cadmium exposure, both glutamine and glutamate contents decreased in the median
      eminence and in anterior and posterior hypothalamus. Metal exposure also
      decreased aspartate content in anterior and posterior hypothalamus, but increased
      it in prefrontal cortex. GABA content decreased in any studied brain region after
      cadmium administration. Besides, the metal decreased taurine content in the
      median eminence, anterior and posterior hypothalamus and in prefrontal cortex.
      The results suggest that cadmium effects on plasma prolactin levels may be
      partially explained by the changes in aspartate, glutamate or taurine contents,
      but not by the decrease in GABA content in the brain regions studied.

PMID- 12224763
TI  - Gene modulation in total brain induced by exposure to the bicyclic phosphorus
      ester trimethylolpropane phosphate (TMPP).
AB  - The effect of a single subconvulsive dose of the GABAergic convulsant
      trimethylolpropane phosphate (TMPP) on gene expression in total rat brain was
      examined using cDNA array analysis. Using threshold criteria that reduce the
      number of false positives to <1 gene per 3551 actively transcribed genes on the
      cDNA array, 41 genes/EST sequences were reproducibly modulated in response to
      0.25 mg/kg TMPP. Several genes that were consistent with epileptogenesis and/or
      neuronal damage and repair mechanisms, such as trkB, alphaB-crystallin, and
      decorin, were modulated by TMPP exposure in the absence of clinical convulsions.
      Previous research indicates that rats exposed to subconvulsive doses of TMPP
      exhibit both "absence-like" EEG paroxysms and persisting central nervous system
      (CNS) sensitization, as evidenced by increased susceptibility to audiogenic
      seizures (AGS). Results of this study suggest that cDNA arrays can be used to
      identify gene modulation events induced by low-level exposure to a chemical
      convulsant in a reproducible manner.

PMID- 12224764
TI  - Fast axonal transport: a site of acrylamide neurotoxicity?
AB  - The cellular and molecular site and mode of action of acrylamide (ACR) leading to
      neurotoxicity has been investigated for four decades, without resolution.
      Although fast axonal transport compromise has been the central theme for several
      hypotheses, the results of many studies appear contradictory. Our analysis of the
      literature suggests that differing experimental designs and parameters of
      measurement are responsible for these discrepancies. Further investigation has
      demonstrated consistent inhibition of the quantity of bi-directional fast
      transport following single ACR exposures. Repeated compromise in fast anterograde
      transport occurs with each exposure. Modification of neurofilaments,
      microtubules, energy-generating metabolic enzymes and motor proteins are
      evaluated as potential sites of action causing the changes in fast transport.
      Supportive and contradictory data to the hypothesis that deficient delivery of
      fast-transported proteins to the axon causes, or contributes to, neurotoxicity
      are critically summarized. A hypothesis of ACR action is presented as a framework
      for future investigations.

PMID- 12224765
TI  - The role of fast axonal transport in acrylamide pathophysiology: mechanism or
      epiphenomenon?

PMID- 12224766
TI  - How does acrylamide perturb axon transport and induce nerve fiber degeneration?
      Commentary on forum position paper.

PMID- 12224767
TI  - Polynomial-based optical true-time delay devices with microelectromechanical
      mirror arrays.
AB  - We previously reported optical true-time delay devices, based on the White cell,
      to support phased-array radars. In particular, we demonstrated a quadratic
      device, in which the number of delays obtainable was proportional to the square
      of the number of times the light beam bounced in the cell. Here we consider the
      possibilities when a microelectromechanical (MEM) tip/tilt mirror array with
      multiple stable states is used. We present and compare designs for quadratic,
      quartic, and octic cells using MEM mirror arrays with two, three, and five micro
      mirror tilt angles. An octic cell with a three-state MEM can produce 6,339
      different delays in just 17 bounces.

PMID- 12224768
TI  - Information hiding technique with double phase encoding.
AB  - We propose a technique for information hiding using double phase encoding. The
      proposed method uses a weighted double phase-encoded hidden image added to a host
      image referred to as the transmitted image. We develop an analytical presentation
      for the system performance using the statistical properties of double phase
      encoding. The peak signal-to-noise-ratio metric is used as a measure for the
      degradation in the quality of the host image and the recovered hidden image. We
      test, analytically, the distortion of the hidden image that is due to the host
      image and the effect of occlusion of the pixels of the transmitted image (that
      is, the host image containing the hidden image). Moreover, we discuss the effect
      of using only the real part of the transmitted image to recover the hidden image.
      Computer simulations are presented to test the system performance against these
      types of distortion. The simulations illustrate the system ability to recover the
      hidden image under distortions and the robustness of the hidden image against
      removal trials.

PMID- 12224769
TI  - Fringe pattern demodulation with a two-frame digital phase-locked loop algorithm.
AB  - A novel technique called a two-frame digital phase-locked loop for fringe pattern
      demodulation is presented. In this scheme, two fringe patterns with different
      spatial carrier frequencies are grabbed for an object. A digital phase-locked
      loop algorithm tracks and demodulates the phase difference between both fringe
      patterns by employing the wrapped phase components of one of the fringe patterns
      as a reference to demodulate the second fringe pattern. The desired phase
      information can be extracted from the demodulated phase difference. We tested the
      algorithm experimentally using real fringe patterns. The technique is shown to be
      suitable for noncontact measurement of objects with rapid surface variations, and
      it outperforms the Fourier fringe analysis technique in this aspect. Phase maps
      produced withthis algorithm are noisy in comparison with phase maps generated
      with the Fourier fringe analysis technique.

PMID- 12224770
TI  - Fringe pattern demodulation with a two-dimensional digital phase-locked loop
      algorithm.
AB  - A novel technique called a two-dimensional digital phase-locked loop (DPLL) for
      fringe pattern demodulation is presented. This algorithm is more suitable for
      demodulation of fringe patterns with varying phase in two directions than the
      existing DPLL techniques that assume that the phase of the fringe patterns varies
      only in one direction. The two-dimensional DPLL technique assumes that the phase
      of a fringe pattern is continuous in both directions and takes advantage of the
      phase continuity; consequently, the algorithm has better noise performance than
      the existing DPLL schemes. The two-dimensional DPLL algorithm is also suitable
      for demodulation of fringe patterns with low sampling rates, and it outperforms
      the Fourier fringe analysis technique in this aspect.

PMID- 12224771
TI  - Digital three-dimensional image correlation by use of computer-reconstructed
      integral imaging.
AB  - We use integral images of a three-dimensional (3D) scene to estimate the
      longitudinal depth of multiple objects present in the scene. With this
      information, we digitally reconstruct the objects in three dimensions and compute
      3D correlations of input objects. We investigate the use of nonlinear techniques
      for 3D correlations. We present experimental results for 3D reconstruction and
      correlation of 3D objects. We demonstrate that it is possible to perform 3D
      segmentation of 3D objects in a scene. We finally present experiments to
      demonstrate that the 3D correlation is more discriminant than the two-dimensional
      correlation.

PMID- 12224772
TI  - Wave-front sensing from defocused images by use of wave-front slopes.
AB  - We describe a novel technique for deriving wave-front aberrations from two
      defocused intensity measurements. The intensity defines a probability density
      function, and the method is based on the evolution of the cumulative density
      function of the intensity with light propagation. In one dimension, the problem
      is easily solved with a histogram specification procedure, with a linear
      relationship between the wave-front slope and the difference in the abscissas of
      the histograms. In two dimensions, the method requires use of a Radon transform.
      Simulation results demonstrate that good reconstructions can be attained down to
      100 photons in each detector. In addition, the method is insensitive to
      scintillation at the aperture.

PMID- 12224773
TI  - High-accuracy position and orientation measurement of extended two-dimensional
      surfaces by a phase-sensitive vision method.
AB  - We introduced recently phase measurements usually performed in interferometry to
      the domain of image processing and intelligent vision [IEEE Trans. Instrum. Meas.
      49, 867 (2000)]. Our purpose is to sense with a high accuracy the position,
      orientation, and displacement of two-dimensional (2D) surfaces observed by a
      static vision system. We report on significant improvements of the method.
      Experimental measurements reveal a peak-valley noise of approximately 10(-2) CCD
      pixel, corresponding approximately to a 10(-3) period of the phase reference
      pattern. Then the observation of 10 microm scaled features enables an accuracy of
      a few nm in the position sensing of the phase reference pattern for the extended
      2D measurement range.

PMID- 12224774
TI  - Amplitude and phase recovery of rotationally symmetric beams.
AB  - Two methods are presented for the amplitude and phase recovery of optical beams
      with rotational symmetry. These are the tomographic method based on the ambiguity
      function and the one-step wavefront recovery based on the measurement of a phase
      space distribution closely related to the Wigner distribution function. The
      results obtained from these two methods are compared, and the appropriateness of
      using either one of them for specific situations is discussed.

PMID- 12224775
TI  - Improvement of the regularized phase tracking technique for the processing of
      nonnormalized fringe patterns.
AB  - One of the powerful approaches to demodulate a single fringe pattern is the
      regularized phase tracking (RPT) technique. Here, a new improvement in the RPT
      technique is presented. This new improvement consists in the addition of one term
      that models the fringe-pattern modulation. With this new term, the RPT technique
      can be used for the demodulation of nonnormalized fringe patterns. The
      performance of the improved RPT technique is shown on examples of various fringe
      patterns.

PMID- 12224776
TI  - Optical on-line running reconstruction of MR-images in the phase-scrambling
      Fourier-imaging technique.
AB  - Recently, the use of magnetic-resonance-guided navigation to improve the safety
      and effectiveness of surgical procedures has shown great promise. The purpose of
      the present study was to develop and demonstrate an imaging strategy that allows
      surgeons to continue operating without delays caused by imaging. The phase
      scrambling Fourier-imaging technique has two prominent characteristics: localized
      image reconstruction and holographic image reconstruction. The combination of
      these characteristics allows images to be observed even during the data
      acquisition period, because the acquired signal is converted into a hologram and
      the image is reconstructed instantly in the coherent optical image-processing
      system. Experimental studies have shown that the phase-scrambling Fourier-imaging
      technique enables the motion of objects to be imaged more quickly than the
      standard fast imaging. The proposed running reconstruction strategy can be easily
      implemented in the well-established magnetic-resonance imaging equipment that is
      currently in use.

PMID- 12224777
TI  - Simple integration technique to realize parallel optical interconnects:
      implementation of a pluggable two-dimensional optical data link.
AB  - An assembly technique is presented to realize pluggable or fully integrated
      optoelectronic systems based on image relays. A method to visually align and
      assemble optoelectronic chips or fiber bundles to half of a relay is explained.
      To validate this technique, two-dimensional arrays of vertical-cavity surface
      emitting lasers and photodetectors and a fiber image guide have been integrated
      to gradient index lenses with simple optomechanical parts. Although the
      connection of these modules was realized with +/-0.5 mm lateral tolerances,
      parallel optical interconnects were successfully achieved at 10 MHz. The lateral
      misalignment between chips was on average 20 microm and at worst 60 microm.

PMID- 12224778
TI  - 512-channel vertical-cavity surface-emitting laser based free-space optical link.
AB  - A vertical-cavity surface-emitting laser based bidirectional free-space optical
      interconnect has been implemented to interconnect two printed circuit boards. A
      total of 512 clustered channels with a density of 2844 channels/cm2 are
      transmitted over a distance of 83 mm. The optical interconnect is a combination
      of refractive microlenses and diffractive minilens relays.

PMID- 12224779
TI  - Viewing-angle enhancement of speckle-reduced volume holographic three-dimensional
      display by use of integral imaging.
AB  - In a conventional integral imaging system the viewing angle is limited by the f
      number of the microlens. To overcome this limitation we employ a phase-conjugate
      beam to read out elemental images, which are stored in photorefractive volume
      holographic storage, while the rotating diffuser reduces the speckle noise. In
      the proposed system the viewing angle can be enhanced over the f-number
      limitation. Experimental results and discussions of viewing parameters are
      presented.

PMID- 12224780
TI  - Free-space wavelength-multiplexed optical scanner demonstration.
AB  - Experimental demonstration of a no-moving-parts free-space wavelength-multiplexed
      optical scanner (W-MOS) is presented. With fast tunable lasers or optical filters
      and planar wavelength dispersive elements such as diffraction gratings, this
      microsecond-speed scanner enables large several-centimeter apertures for
      subdegree angular scans. The proposed W-MOS design incorporates a unique optical
      amplifier and variable optical attenuator combination that enables the
      calibration and modulation of the scanner response, leading to any desired
      scanned laser beam power shaping. The experimental setup uses a tunable laser
      centered at 1560 nm and a 600-grooves/mm blazed reflection grating to accomplish
      an angular scan of 12.92 degrees as the source is tuned over an 80-nm bandwidth.
      The values for calculated maximum optical beam divergance, required wavelength
      resolution, beam-pointing accuracy, and measured scanner insertion loss are 1.076
      mrad, 0.172 nm, 0.06 mrad, and 4.88 dB, respectively.

PMID- 12224781
TI  - Tunable photonic crystal microcavities.
AB  - We present a method for tuning a photonic crystal microcavity by modulating the
      index of refraction of the lattice sites within and surrounding the microcavity.
      The index of refraction can be actively modulated after infiltrating anisotropic
      liquid crystals into a two-dimensional photonic crystal lattice of air cylinders
      in silicon. We analyze the Q-factors and resonance frequencies of a tunable
      photonic crystal microcavity by considering various methods of index modulation.
      These tunable cavities are incorporated in a channel drop filter to demonstrate
      their enhancement of wavelength division multiplexing photonic crystal
      applications.

PMID- 12224782
TI  - Association between passive cigarette smoking and the risk of developing acute
      coronary syndromes: the CARDIO2000 study.
AB  - Although the effect of smoking on human health has been established as a major
      risk factor, the effect of passive smoking is controversial. The purpose of this
      study was to investigate the association between passive smoking and the risk of
      acute coronary syndromes (ACS) among nonsmokers. Eight hundred and forty-eight
      patients with the first event of ACS and 1078 cardiovascular disease-free matched
      controls completed a detailed questionnaire regarding their exposure to
      environmental smoke. Two hundred and ninety-seven (35%) of the patients and 259
      (24%) of the controls were defined as nonsmokers and passive smokers,
      respectively. After controlling for several potential confounders, the results
      showed that nonsmokers exposed to cigarette smoke increased the risk of ACS by
      51% (odds ratio = 1.51, 95% confidence interval 1.21-2.99) compared with
      nonsmokers not exposed to smoke. It was estimated that 34 coronary events per 134
      subjects would occur as a result of passive smoking during their lifetime.
      Consequently, this study supports the hypothesis that passive smoking increases
      the risk of developing acute coronary syndromes. Given the high prevalence of
      cigarette smoking in many developing societies, the public health consequences of
      passive smoking with regard to coronary heart disease may be important.

PMID- 12224783
TI  - Detection of myocardial ischemia in the elderly versus the young by stress
      thallium-201 scintigraphy and its relation to important coronary artery disease.
AB  - The prevalence and severity of coronary atherosclerosis increase dramatically
      with age, so that more than half of all deaths in persons aged over 65 are due to
      coronary arterial disease (CAD) and about three fourths of all deaths from CAD
      occur in the elderly. The aims of our study were, first, to detect myocardial
      ischemia development in elderly versus younger patients undergoing treatment for
      known CAD through the use of both conventional treadmill testing and 201T1
      scintigraphy, and second, to determine the relationship between the above non
      invasive tests and angiographically confirmed important coronary artery disease
      (iCAD). A database of 606 patients (355 men and 251 women) who had undergone
      coronary angiography, exercise ECG testing (ETT) using the treadmill Bruce
      protocol, and 201T1 scintigraphy, was reviewed retrospectively. All patients had
      displayed clinical expression of CAD with or without the existence of an old
      myocardial infarction (MI). The patients were from both sexes (440 men and 252
      women) and divided into two groups, according to age. Group A was composed of 265
      patients aged over 65 (170 men, 95 women, mean age = 70.3 +/- 5.3 years). Group B
      was composed of 341 patients aged under 65 (185 men, 156 women, mean age 54.4 +/-
      9.1 years). Patients with uncontrolled arterial hypertension, hypertrophic
      cardiomyopathy, severe valve diseases, severe chronic obstructive lung diseases,
      severe anemia, peripheral atherosclerosis, orthopedic problems, or Parkinson's
      disease were excluded from the study. The term "important coronary artery
      disease" (iCAD) covers the following patterns of coronary anatomy: (a) left main
      stem stenosis > or = 50% with or without disease elsewhere, (b) proximal three
      vessel disease, (c) three-vessel disease including the proximal left anterior
      descending artery (LAD), (d) proximal two-vessel disease including LAD, and (e)
      two-vessel disease including the proximal LAD. Biostatistical characteristics
      such as sensitivity, specificity, and predictive values of ETT-201T1 were
      estimated. Analyzing our results we concluded that: the biostatistical parameters
      in predicting important CAD in elderly and younger patients by means of exercise
      test and thallium scintigraphy need to be redefined through more closely
      scheduled and prospective studies; in elderly coronary patients, the appearance
      of positive results in both parameters of ETT-201T1 indicates a significant
      possibility of iCAD existence; in coronary patients younger than 65 years, the
      appearance of negative results in both parameters of ETT-201T1 almost excludes
      iCAD, in contrast to elderly patients, who display a significant proportion of
      iCAD; in elderly coronary patients, the appearance of equivocal results in both
      tests indicates a significant possibility of the existence of iCAD, in contrast
      to younger patients.

PMID- 12224784
TI  - Chlamydia pneumoniae seropositivity predicts the risk of restenosis after
      percutaneous transluminal coronary angioplasty.
AB  - This study was done to evaluate whether anti-Chlamydia pneumoniae seropositivity
      can be a predictor of restenosis after coronary intervention. Recent studies
      indicate that latent infection with C. pneumoniae is associated with and could
      possibly cause atherosclerosis. However, it is unknown whether chronic infection
      with this microorganism is involved in the mechanism of restenosis after
      percutaneous transluminal coronary angioplasty. We prospectively studied 78
      consecutive patients (90 target lesions) with symptomatic coronary artery disease
      who underwent successful coronary intervention to a de novo lesion (conventional
      balloon angioplasty to 31 lesions and stent implantation to 59 lesions). At
      angioplasty, blood samples were collected to measure the serum level of anti-C.
      pneumoniae IgG to examine whether seropositive patients were prone to restenosis
      and whether the seropositivity could predict the risk of restenosis determined by
      follow-up coronary angiography performed within 6 months after the angioplasty.
      Restenosis, defined as more than 50% stenosis with an increase of 15% or more in
      the degree of stenosis from that measured on cineangiograms after angioplasty,
      developed in 36 of 62 seropositive patients and in 4 of 16 seronegative patients
      (58% vs 25%, P = 0.025). Lesions in the seropositive patients had a greater mean
      loss index (mean +/- SD 0.75 +/- 0.45 vs 0.35 +/- 0.41, P < 0.001), which was
      defined as late loss (luminal diameter reduction at follow-up angiography)
      divided by acute gain (luminal diameter gain by angioplasty), in late loss (1.07
      +/- 0.64mm vs 0.65 +/- 0.79mm, P = 0.019), in percentage of diameter stenosis
      (57% +/- 20% vs 41% +/- 21%, P = 0.003) and a lesser mean in minimal luminal
      diameter (1.18 +/- 0.58 mm vs 1.67 +/- 0.63 mm, P = 0.002) at follow-up
      angiography. In a multivariate logistic regression model, anti-C. pneumoniae IgG
      seropositivity was a strong independent predictor of restenosis compared to the
      other risk factors (odds ratio = 6.2, P = 0.01). C. pneumoniae could play an
      important role in the mechanism of restenosis and evaluation of the IgG
      seropositivity, and may help to identify patients at high risk for restenosis.

PMID- 12224785
TI  - The relationship of ST segment elevation shape with preserved myocardium and
      signal-averaged electrocardiography in acute anterior myocardial infarction.
AB  - Although a relation between magnitude of ST segment elevation and myocardial
      damage has been shown in the early period of acute myocardial infarction (AMI),
      such a relation between the shape of the ST segment elevation, myocardial damage,
      and the clinical course remains obscure. For this purpose 62 first anterior AMI
      patients admitted in the first 6h were enrolled for the study. On the basis of
      precordial V3 derivation prior to thrombolytic therapy, the shape of the ST
      elevation was separated into three groups: concave (n = 26), straight (n = 24),
      or convex types (n = 12). The relation between the shape of the ST elevation
      recorded on admission, and the results of pre-discharge low-dose dobutamine
      stress echocardiography (LDE) performed (n = 53) and signal-averaged ECG values
      were investigated. The basal wall motion score index (WMSI) and response to LDE
      in the concave group were better in the infarct zone. Additionally, the average
      akinetic segment number in the infarct zone was higher, and improvement in these
      segments was less in the convex and straight groups (concave 3.78 +/- 2 vs 2.17
      +/- 2.1, P < 0.01; straight 5.15 +/- 2.7 vs 4.45 +/- 2.8, not significant (NS);
      convex 5.4 +/- 2.3 vs 4.8 +/- 2.1, NS; basal vs LDE). While only 13% (3/23) of
      the patients did not respond to LDE (P < 0.05 vs group B and P < 0.01 vs group
      C), 35% (7/20) of group B and 60% (6/10) of group C patients did not respond to
      LDE. Although no relation was found between better left ventricular function
      (WMSI < 2) and shape of the ST elevation in basal evaluation by multiple logistic
      regression analysis (P = 0.06), an independent relation was found between them
      following LDE (P = 0.01, odds ratio (OR) 4.5, 95% Confidence Interval (CI) 1.3
      14.7). The incidence of ventricular late potential (LP) positivity was 11% (3/26)
      in the concave group, 16% (4/24) in the straight group, and 58% (7/12) in the
      convex group (P < 0.001 vs concave and P < 0.05 vs straight groups). We found
      that shape of the ST elevation could significantly predict the presence of late
      potentials in multiple logistic regression analysis (P = 0.003, OR 10.7, 95% CI
      2.2-51.7). There was no in-hospital death in the concave group, whereas five
      patients died in either the straight or the convex group. Furthermore, arrhythmia
      was lower in the concave group during this period (P < 0.05), and exercise
      capacity was lower. In conclusion, we determined that there was a higher viable
      myocardium, and lower LP(positivity) and in-hospital mortality in patients with
      concave ST elevation on admission.

PMID- 12224786
TI  - Amiodarone distribution in human tissues after long-term therapy: a case of
      arrhythmogenic right ventricular cardiomyopathy.
AB  - The tissue distribution of amiodarone and desethylamiodarone, its active
      metabolite, was examined in an autopsied case, an 85-year-old man, with
      arrhythmogenic right ventricular cardiomyopathy (ARVC) who had been receiving
      amiodarone for 4 years. High concentrations of amiodarone, a very highly
      lipophilic compound, were found in adipose and bone marrow tissues. Despite a low
      dose (100 mg daily), the concentrations of amiodarone were higher in the
      epicardial fat (570.4 microg/g) and in the right atrium (165.3 microg/g) than
      previously reported in patients with other cardiac diseases. The ratios of
      amiodarone/ desethylamiodarone concentrations in both tissues were >1. This
      unique distribution demonstrates the involvement of histological characteristics
      of ARVC, such as fatty replacement of myocardium. We anticipate that a low dose
      of amiodarone would be effective in preventing arrhythmia in some patients with
      ARVC.

PMID- 12224787
TI  - Primary systemic amyloidosis presenting as angina pectoris due to intramyocardial
      coronary artery involvement: a case report.
AB  - We describe a 76-year-old Japanese woman with primary systemic amyloidosis who
      presented with angina pectoris associated with ST-segment and T-wave
      abnormalities resulting from intramyocardial coronary artery amyloidosis. The
      patient was admitted to our hospital because of dyspnea and pretibial edema 7
      years after the diagnosis of variant angina. A diagnosis of primary systemic
      amyloidosis (AL amyloid protein) was made after examination of gastric and
      endomyocardial biopsy specimens. The patient died of progressive, uncontrolled
      heart failure 3 months later. An autopsy study demonstrated only mild-to-moderate
      atherosclerosis in the epicardial coronary arteries. However, histological
      examination of the heart revealed diffuse stenoses and obstructions in the
      intramural coronary arteries by amyloid deposits. This patient had small-vessel
      coronary disease with ST-segment changes and angina caused by cardiac
      amyloidosis. A correct diagnosis of ischemic heart disease due to primary
      amyloidosis is important for estimation of the prognosis and for appropriate
      management.

PMID- 12224789
TI  - Extracorporeal membrane oxygenation and left ventricular assist device: a case of
      double mechanical bridge.
AB  - A 14-year-old boy with dilated cardiomyopathy with cardiac arrest was
      successfully implanted with a left ventricular assist device (LVAD) after 6-day
      extracorporeal membrane oxygenation (ECMO). He had multiple organ failure at the
      initiation of ECMO, but the failed organs recovered during assisted circulation,
      leading to LVAD implantation. This case showed the advantages of the "double
      bridge" such as: (1) quick and easy installation for acute cardiogenic shock, (2)
      providing intervention time for complications refractory to LVAD implantation,
      and (3) providing evaluation time for potential LVAD implantation and transplant
      candidates.

PMID- 12224788
TI  - Single coronary artery with anomalous origin of the right coronary artery as a
      branch from the left anterior descending artery: a very rare coronary anomaly.
AB  - Anomalous origin of the right coronary artery arising from the left anterior
      descending artery (LAD) is a very rare coronary anomaly. It has previously been
      reported in only six adult cases. In this report, we present a patient with an
      anomalous origin of the right coronary artery from the LAD. The patient had
      anginal symptoms with exercise. Myocardial perfusion imaging with thallium-201
      revealed a reversible inferior perfusion defect. We suggest that this could cause
      myocardial ischemia.

PMID- 12224790
TI  - Detection of muftiple regurgitation during mitral valvuloplasty by multiangle
      four-dimensional color Doppler echocardiography.

PMID- 12224791
TI  - The hope for a self-healing brain.

PMID- 12224792
TI  - Molecular aspects of neurodegeneration in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a degenerative disease of the brain, and the most
      common form of dementia. It is estimated that more than 22 million individuals
      worldwide will have AD by 2025. The causes of the disease are still unknown and
      recent hypotheses suggest that an aberrant protein processing initiates the
      neurodegeneration. Several lines of research are centered on the study of
      proteins that are genetically associated with this syndrome, such as amyloid
      precursor protein (APP) and presenilins. This review focuses on recent advances
      in the processing of APP and on the neuropathological role of its amyloidogenic
      fragments, which have been shown to be directly involved in neurodegeneration and
      glial inflammation and which likely influence the development of AD.

PMID- 12224793
TI  - Complex distal movement in cortical-basal ganglionic degeneration. A functional
      evaluation.
AB  - We evaluated cortical activation during simple and complex learned movements in
      five patients diagnosed with cortical-basal ganglionic degeneration. Since the
      parietal area is one of the areas most involved in this degenerative pathology,
      we focused on the possible role of the parietal lobe, in learning and executing
      simple and complex motor sequences. We also attempted to describe the role of the
      parietal area in spatial and visual control, which is necessary to define and
      optimise movement execution in daily living. We discuss the results of our
      evaluation, and give an overview of the literature on the topic.

PMID- 12224794
TI  - Normal sympathetic nervous system response in reflex sympathetic dystrophy.
AB  - We evaluated sympathetic nervous system activity by sympathetic skin response
      (SSR) recording and we further investigated sympathetic and opioid outflow
      indirectly in patients with features of reflex sympathetic dystrophy by measuring
      concentrations of plasma catecholamines (CAs) and their metabolites and plasma
      metenkephalin (ME), before and after corticoid treatment. Six patients were
      studied. Basal SSR latencies, morphologies and amplitudes were normal in five
      patients. In one woman, latency and amplitude were also normal but the morphology
      was disturbed. Basal plasma ME, CA and metabolite levels were similar in the
      affected and non-affected limbs and a significant increase in plasma ME
      concentrations was observed in both affected and non-affected limbs after two
      weeks of steroid treatment. Altogether these results point to an adaptive
      supersensitivity rather than a sympathetic hyperactivity in this syndrome; also,
      they indicate that the therapeutic effect of steroids adds, to their known anti
      inflammatory action, a stimulatory action on the endogenous opioid system.

PMID- 12224795
TI  - Cognitive impairment and central motor conduction time in chronic alcoholics.
AB  - The non-invasive technique of transcranial magnetic stimulation (TMS) was used in
      62 chronic alcoholics to assess the functional status of descending motor
      pathways. The main aims of this study were: to investigate asymptomatic upper
      motor neuron dysfunction in alcoholics as well as to assess its relationship with
      parameters reflecting the intensity of exposure to alcohol; and to evaluate a
      possible relationship between central motor conduction time (CMCT) prolongation
      and neuropsychological measures of alcohol-related brain damage. Compared to
      control subjects, chronic alcoholics exhibited a significant prolongation of CMCT
      (23 out of 62 subjects). No significant correlation was found between CMCT
      prolongation and intensity and duration of abuse, presence of peripheral
      neuropathy, or brain atrophy on CT scans. Prolongation of CMCT from the upper
      limb correlated significantly with impairment of frontal skills on
      neuropsychological testing (p<0.01). These findings suggest that TMS may be a
      sensitive method for the detection in alcoholics of subtle neurological
      dysfunction, not confined to motor pathways.

PMID- 12224796
TI  - Visual acuity in the first two years of life in healthy term newborns: an
      experience with the teller acuity cards.
AB  - Teller Acuity Cards are a new "preferential looking" procedure for the evaluation
      of visual acuity in newborns and infants. We used this test to assess,
      longitudinally, visual acuity in 60 healthy term newborns followed up from birth
      to two years of age. In order to have a set of comparison parameters for use in
      studies of newborns at risk of developing visual system impairment, the relative
      maturational curve was plotted. The acuity values of our sample are in line with
      those reported by other authors in the literature and they represent the first
      set of such data referring to a group of healthy term newborns in Italy. This
      paper provides a visual acuity curve for the first two years of life obtained
      from healthy term newborns, a curve which could prove useful for reference when
      this technique is used on newborns at risk of developing neurological and
      especially visual problems.

PMID- 12224797
TI  - Is there a role for uridine and pyrimidine nucleosides in the treatment of
      vascular dementia?
AB  - In the 70s, the discovery of a constant loss of acetylcholine (Ach) in the brains
      of people suffering from dementia led to the development, in order to improve
      cognitive functions, of drugs that increased Ach levels. The possibility that
      loss of a given neurotransmitter might be associated with the onset of a specific
      neurological syndrome led to suggestions that, as had already been found in
      Parkinson's disease, replacement therapy might drastically improve the course of
      the syndrome. We are now aware of the limits of this therapeutic approach. In
      this review, we analyse potential factors contributing to the partial failure of
      Ach replacement therapy, contrasting common beliefs regarding the Ach synapse
      with the difficulties in restoring its activity through replacement drugs.
      Considering the search for alternative strategies, in the second part of the
      review, we overview progress of research into pyrimidine compounds, now emerging
      as a new modulatory system acting through specific pyrimidino-receptors involved
      in various steps of cell signalling. Pyrimidine nucleosides might be useful in
      the chronic treatment of cognitive deficits resulting from vascular dementia.

PMID- 12224798
TI  - Traumatic stress responses in earthquake survivors in Turkey.
AB  - This study examined the rates of posttraumatic stress disorder (PTSD) and
      depression and associated risk factors in earthquake survivors in Turkey. A group
      of 1,000 people from 3 camps and 2 prefabricated housing sites in the epicenter
      region was assessed using the Screening Instrument for Traumatic Stress in
      Earthquake Survivors. The estimated rates of PTSD and major depression were 43
      and 31 %, respectively. Traumatic stress symptoms related to more intense fear
      during the earthquake, female gender, having been trapped under rubble, death of
      a family member, past psychiatric illness, having participated in rescue work,
      and lower education. Avoidance of trauma reminders was the most common symptom
      and needs special attention in survivor care because of its mental health,
      social, and economic implications.

PMID- 12224799
TI  - Traumatic stress symptoms among women with recently diagnosed primary breast
      cancer.
AB  - This study examined the concurrent and longitudinal relationships between
      traumatic stress symptoms and demographic, medical, and psychosocial variables
      among women recently diagnosed with primary breast cancer. Participants were 117
      women drawn from a parent study for women recently diagnosed with primary breast
      cancer. At baseline, the Impact of Event Scale (IES) total score was related to
      intensity of postsurgical treatment and lower emotional self-efficacy. At the 6
      month follow-up, the IES total score was significantly related to younger age, to
      the increased impact of the illness on life, and to the baseline IES total score
      assessment. These results suggest that it is important to intervene for traumatic
      stress symptoms soon after the diagnosis of breast cancer. Furthermore, these
      results suggest women at greatest risk are those who are younger, who receive
      postsurgical cancer treatment, who are low in emotional self-efficacy and whose
      lives are most affected by having cancer.

PMID- 12224800
TI  - Emotional adjustment in survivors of sexual assault living with HIV-AIDS.
AB  - This study examined history of sexual assault in 357 men and women living with
      HIV-AIDS. Participants completed measures of demographic characteristics, sexual
      assault history, emotional distress and psychiatric symptoms, substance use, and
      sexual behaviors. Results showed that 68% of women and 35% of men living with HIV
      AIDS reported a history of sexual assault since age 15. History of sexual assault
      was related to history of substance use and mental health treatment. Sexual
      assault survivors reported greater anxiety, depression, and symptoms of
      borderline personality and were significantly more likely to report recent
      unprotected intercourse than persons who had not been sexually assaulted. Results
      suggest tailoring secondary prevention interventions to meet the needs of HIV
      positive survivors of sexual assault.

PMID- 12224801
TI  - Civilian-based posttraumatic stress disorder and physical complaints: evaluation
      of depression as a mediator.
AB  - This study examined the role of comorbid depression in the somatic complaints of
      32 individuals with civilian-based posttraumatic stress disorder (PTSD) while
      restricting the influence of detectable pathophysiology and additional
      psychiatric conditions. It was hypothesized that depressive symptomatology would
      mediate the relationship between PTSD and somatic symptom reporting. Participants
      were administered structured clinical interviews, a physical examination, and an
      electrocardiogram. Results of this study supported the hypothesis that depressive
      symptoms mediate the relationship between PTSD and physical complaints. These
      results add to a growing body of literature that suggests psychological factors
      play an influential role in the physical symptom reports of individuals with
      PTSD.

PMID- 12224802
TI  - Traumatic events and physical health in a New Zealand community sample.
AB  - Traumatic event exposure and physical health were examined in a community
      residing sample of 1,500 New Zealand adults. Half (51%) reported past traumatic
      event exposure, 9% reported recent (past 12 months) trauma exposure, and 40%
      reported no exposure. After adjusting for gender, ethnic, and age differences,
      those experiencing crime and accident trauma exhibited significantly deteriorated
      physical health, as measured by current physical symptoms, chronic medical
      conditions, and chronic limitations in daily functioning. Further research is
      required to assess the influence of traumatic events on the physical health among
      adults from other countries, and to evaluate the factors that may mediate or
      moderate this relationship for different subgroups of the New Zealand population.
      Limitations of this study are outlined.

PMID- 12224803
TI  - Supercyclone in Orissa: an assessment of psychological status of survivors.
AB  - The study assessed the impact of the Orissa supercyclone on survivors' locus of
      control, anxiety, depression, and posttraumatic stress. The study was conducted
      in structured interview sessions 3 months after the supercyclone. The affected
      people (n = 65) who were close to the epicenter of supercyclone and lost their
      family members, relatives, and property, experienced more anxiety, depression,
      and posttraumatic stress than the unaffected (n = 65) who were away from the
      epicenter of supercyclone and had not experienced any loss. Effects of exposure
      remained significant with the effects of sex and neuroticism controlled. External
      support reduced anxiety and depression, and the amount of loss experienced by the
      survivors significantly increased external locus of control and anxiety.

PMID- 12224804
TI  - A preliminary investigation of alcohol use during trauma and peritraumatic
      reactions in female sexual assault victims.
AB  - The purpose of these analyses was to investigate the association between reported
      alcohol use during a sexual assault and perceptions of assault severity and
      physical and emotional peritraumatic reactions. Self-report data were collected
      on 57 sexually assaulted college women. Multivariate regression analyses revealed
      that perception of assault severity mediated the relationship between alcohol use
      and peritraumatic physical reactions.

PMID- 12224805
TI  - An evaluation of patient satisfaction with an information leaflet for trauma
      survivors.
AB  - A new leaflet that provided information about posttraumatic reactions and how to
      deal with them was distributed within 14 days of attendance at the Accident and
      Emergency Department (ED), Aberdeen Royal Infirmary, to a heterogeneous sample of
      trauma patients (N = 222). An evaluation form to assess satisfaction with the
      leaflet was also mailed with the leaflet. A sample of 98 (44%) of the initial
      patient group responded, and 96% of them reported the leaflet as either very
      helpful or helpful. Satisfaction with the leaflet was not affected by age, by
      gender, or by the type of trauma encountered. Overall, the findings confirmed
      that such a leaflet is well received by trauma patients attending an ED.

PMID- 12224806
TI  - Motor vehicle crash versus accident: a change in terminology is necessary.
AB  - We assert that motor vehicle crash should replace motor vehicle accident in the
      clinical and research lexicon of traumatologists. Crash encompasses a wider range
      of potential causes for vehicular crashes than does the term accident. A majority
      of fatal crashes are caused by intoxicated, speeding, distracted, or careless
      drivers and, therefore, are not accidents. Most importantly, characterizing
      crashes as accidents, when a driver was intoxicated or negligent, may impede the
      recovery of crash victims by preventing them from assigning blame and working
      through the emotions related to their trauma.

PMID- 12224807
TI  - Memory for frequency of bizarre and common stimuli: limitations of the
      automaticity hypothesis.
AB  - In 2 experiments, the influence of intention to process frequency on accuracy of
      memory for frequency of bizarre and common sentences was investigated. The
      results from multiple regression analyses indicated that intentional processing
      increased the accuracy of frequency judgments when memory for frequency was
      tested after a 2-min (Experiment 1) and after a 48-hr (Experiment 2) retention
      interval. Furthermore, the results of Experiment 2 indicated that unintentional
      processors tended to overestimate frequencies of bizarre relative to common items
      after a delay. The implications of the results are discussed with regard to L.
      Hasher and R. T. Zacks's (1984) automaticity hypothesis, human performance, and
      the accuracy of judgments of frequency of occurrence of unusual events.

PMID- 12224808
TI  - Behavioral effects of chronic melatonin and pregnenolone injections in a myelin
      mutant rat (taiep).
AB  - The taiep (tremor, ataxia, immobility, epilepsy, and paralysis) myelin mutant
      displays a number of locomotor deficits. Taiep rat gait is characterized by
      shorter stride and step lengths as well as by larger stride widths. Thirty-day
      old taiep mutants were placed under a regimen of daily hormone injections for 60
      days. Animals in Condition 1 received melatonin, those in Condition 2 received
      pregnenolone sulfate, and those in a third control condition received injections
      of saline. Following the injections, each taiep mutant's gait was analyzed. The
      animals that received melatonin and pregnenolone displayed significantly larger
      stride and step lengths than did the controls. In addition, the animals that
      received hormones displayed shorter stride widths than did the controls. These
      experimental effects are consistent with a normalization of gait. Possible
      cellular mechanisms of this behavioral effect are discussed.

PMID- 12224809
TI  - The cognitive failures questionnaire revisited: dimensions and correlates.
AB  - The authors reexamined the factor structure of the Cognitive Failures
      Questionnaire (D. E. Broadbent, P. F. Cooper, P. Fitzgerald, & K. R. Parkes,
      1982) and its correlates. The Cognitive Failures Questionnaire was designed to
      assess a person's likelihood of committing an error in the completion of an
      everyday task. A principal components factor analysis with varimax rotation
      yielded 4 internally consistent, interpretable factors. These factors were
      labeled Memory, Distractibility, Blunders, and (memory for) Names. This study
      lends partial support for the factor analytic solution proposed by L. K. Pollina,
      A. L. Greene, R. H. Tunick, and J. M. Puckett (1992). In addition, it extends
      previous findings by providing initial evidence for the construct validity of the
      factors established by correlating factor scores with measures of other related
      constructs (i.e., boredom proneness, attention deficit/hyperactivity disorder,
      Type A behavior pattern).

PMID- 12224810
TI  - The role of individual differences in the accuracy of confidence judgments.
AB  - Generally, self-assessment of accuracy in the cognitive domain produces
      overconfidence, whereas self-assessment of visual perceptual judgments results in
      underconfidence. Despite contrary empirical evidence, in models attempting to
      explain those phenomena, individual differences have often been disregarded. The
      authors report on 2 studies in which that shortcoming was addressed. In
      Experiment 1, participants (N= 520) completed a large number of cognitive-ability
      tests. Results indicated that individual differences provide a meaningful source
      of overconfidence and that a metacognitive trait might mediate that effect. In
      further analysis, there was only a relatively small correlation between test
      accuracy and confidence bias. In Experiment 2 (N = 107 participants), both
      perceptual and cognitive ability tests were included, along with measures of
      personality. Results again indicated the presence of a confidence factor that
      transcended the nature of the testing vehicle. Furthermore, a small relationship
      was found between that factor and some self-reported personality measures. Thus,
      personality traits and cognitive ability appeared to play only a small role in
      determining the accuracy of self-assessment. Collectively, the present results
      suggest that there are multiple causes of miscalibration, which current models of
      over- and underconfidence fail to encompass.

PMID- 12224811
TI  - Entropy, visual diversity, and preference.
AB  - The author reports relationships between subjective impressions of visual
      diversity or pleasure with statistical entropies of stimuli. The stimuli were 34
      rows of houses that varied in color, scale, and shape, or in shape and
      articulation. Entropies ranged from 0.0 to 5.6 bits. Fifty-seven participants
      rated the stimuli on scales of pleasant/unpleasant and uniform/diverse. The
      relationship between rated diversity and entropy was strong and linear. The
      relationship between rated pleasure and entropy was either linear or asymptotic,
      but no evidence was found for an inverted U relationship.

PMID- 12224812
TI  - The Mikamo Lecture 2002. Therapeutic targets for the treatment of
      atherothrombosis in the new millennium--clinical frontiers in atherosclerosis
      research.

PMID- 12224813
TI  - Transcatheter closure of atrial septal defects with the Amplatzer septal occluder
      -a Japanese clinical trial.
AB  - This study reports the results of a Japanese clinical trial of transcatheter
      closure of atrial septal defects (ASD) using the Amplatzer septal occluder (ASO).
      Thirty-five patients with secundum ASD underwent transcatheter closure using the
      ASO at a median age of 12.9 years (range, 3.2-29.2 years) and a median weight of
      39.2kg (range, 11.6-65.1 kg). The ASO was successfully implanted in 34 patients.
      The mean ASD diameter of the 34 patients measured by transesophageal
      echocardiography was 11.7 +/- 4.2mm (range, 5.0-20.8mm) and the mean balloon
      stretched diameter was 16.8 +/- 4.2 mm (range, 9-25 mm). The mean ASO size was
      16.9 +/- 4.3 mm (range, 9-26mm). Complete closure rate at 1 day and 1 year after
      closure was 91% and 97%, respectively. One patient developed a transient second
      degree atrioventricular block during the implantation procedure. No other
      complications occurred. Transcatheter closure of ASD using the ASO is effective
      and safe.

PMID- 12224814
TI  - Perioperative advantages of off-pump coronary artery bypass grafting.
AB  - For the first time in Japan, off-pump coronary artery bypass grafting (OPCAB) was
      compared with the conventional on-pump technique, retrospectively examining the
      morbidity associated with coronary artery bypass grafting (CABG) and assessing
      the efficacy of OPCAB. In 2000, 158 patients underwent CABG: 95 patients (60%)
      had OPCAB (Group I) and 63 patients (40%) had conventional CABG (Group II). The
      operating time, length of intensive care unit (ICU) stay, ventilation time,
      postoperative bleeding, transfusion, postoperative renal function, occurrence of
      stroke, and early graft patency were examined in both groups. There were no
      hospital deaths in either group. The operating time, ICU stay, and ventilation
      time were significantly (p < 0.0001, p = 0.013, and p < 0.0001, respectively)
      shorter in Group I (351 +/- 85 min, 3.0 +/- 1.4 days, and 5.1 +/- 2.8h) than in
      Group II (449 +/- 112 min, 3.6 +/- 1.8 days, and 13.7 +/- 18.0 h). The
      postoperative blood loss within 12h and the transfusion volume were significantly
      (p = 0.0004 and p < 0.0001, respectively) smaller in Group I (480 +/- 210 ml and
      300 +/- 490ml) than in Group II (720 +/- 430ml and 1,230 +/- 1,180 ml). Peak
      serum blood urea nitrogen and creatinine concentrations (excluding patients with
      preoperative chronic renal failure, ie a preoperative serum creatinine > 1.5
      mg/dl) were significantly (p < 0.0001 and p < 0.0001, respectively) lower in
      Group I (16.2 +/- 15.2mg/dl and 0.81 +/- 0.72 mg/dl) than in Group II (19.2 +/-
      7.6 mg/dl and 0.92 +/- 0.28 mg/dl). There were no perioperative strokes in Group
      I, but 6.4% of Group II patients suffered a stroke. There was no significant
      difference in graft patency between the groups (95.6% vs 94.9%). OPCAB reduced
      the mortality and morbidity of coronary revascularization, with a shorter
      operating time and more rapid recovery from surgery.

PMID- 12224815
TI  - Influence of diabetes mellitus on outcome in the era of primary stenting for
      acute myocardial infarction.
AB  - The purpose of the present study was to examine the influence of diabetes
      mellitus (DM) on the clinical and angiographic outcomes in 62 diabetic and 152
      nondiabetic patients with acute myocardial infarction (AMI) treated with primary
      coronary stenting within 12 h of the onset of symptoms. The diabetic patients had
      a greater incidence of hyperlipidemia, prior myocardial infarction (MI) and
      multivessel disease. There were no statistically significant differences in other
      variables. Procedural success was similar in the 2 groups. At a mean follow-up of
      2.1 +/- 0.6 years, 13% of diabetic and 11% of nondiabetic patients had died (p =
      0.70). The percentage of target vessel revascularization (TVR) was 37% of
      diabetic and 20% of nondiabetic patients (p = 0.003). Rates of major adverse
      cardiac events (MACE: death, non-fatal MI, TVR) were 50% of diabetic and 32% of
      nondiabetic patients (p = 0.007). On multivariate analysis, DM was not a
      predictor of death. Independent predictors of death were age, multivessel
      disease, TIMI < or = 2 and cardiogenic shock. However, DM and age were
      independent predictors of MACE. In conclusion, DM is not an independent predictor
      of death in patients with AMI after stenting, but diabetic patients had a higher
      incidence of TVR, making DM an independent predictor of MACE.

PMID- 12224816
TI  - Prevalence of Helicobacter pylori infection and its link to coronary risk factors
      in Japanese patients with acute myocardial infarction.
AB  - The association between Helicobacter pylori (H. pylori) infection and coronary
      artery disease, as well as the association between H. pylori infection and
      classic coronary risk factors, is controversial in patients from Western
      countries. The high prevalence of H. pylori infection in Japanese subjects
      enables an examination of these associations in a large population, especially in
      young patients, because coronary risk factors may be more strongly associated
      with younger individuals than with older individuals. The IgG seropositivity to
      H. pylori was assessed in 618 cases with acute myocardial infarction (AMI) and in
      967 controls. The prevalence of seropositivity to H. pylori was similar between
      cases and controls, but in subjects younger than 55 years, the rate was
      significantly higher in cases than in controls (58.7% vs 43.3%, p = 0.009). After
      adjustment for age, gender, diabetes mellitus, hypertension, smoking, body mass
      index, total cholesterol, and high density lipoprotein cholesterol, the odds
      ratio for acute myocardial infarction was 2.97 (95% confidence interval, 1.37
      6.41; p = 0.006). Worsening of classic coronary risk factors was not associated
      with H. pylori infection in subjects younger than 55 years. These results suggest
      that in younger individuals in Japan, H. pylori infection is significantly
      associated with AMI independent of the classic coronary risk factors.

PMID- 12224817
TI  - Angiotensin-converting enzyme activity is involved in the mechanism of increased
      endogenous nitric oxide synthase inhibitor in patients with type 2 diabetes
      mellitus.
AB  - The renin-angiotensin system plays an important role in the elevation of
      asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide
      synthase, in hypertensive patients, so the present study was designed to examine
      whether angiotensin-converting enzyme (ACE) activity is also involved in the
      mechanism of ADMA elevation in type 2 diabetes mellitus (NIDDM). A crossover
      study was performed to determine if ACE inhibition with perindopril (4 mg/day)
      for 4 weeks decreases serum ADMA concentration and plasma von Willebrand factor
      (vWF) level (a marker of endothelial injury) in 11 patients with NIDDM. None of
      the patients was treated with insulin or oral hypoglycemic drugs, and none had
      major diabetic complications. Before the protocol began, serum ADMA and plasma
      vWF were significantly higher in the 11 NIDDM patients, when compared with 8
      control subjects without diabetes. Perindopril did not affect blood pressure or
      glucose metabolism, but did significantly decrease serum ADMA and plasma vWF.
      These results suggest that endothelial injury associated with ADMA elevation may
      be present even in patients with non-complicated NIDDM, and that increased
      activity of ACE may be involved in such endothelial dysfunction.

PMID- 12224818
TI  - Post radial artery harvest hand perception: postoperative 12-month follow-up
      results.
AB  - The 12-months' follow-up results for radial artery harvest in relation to
      complications are reported and compared with the postoperative 3-months' results.
      The postoperative wound problems of 155 patients who underwent coronary artery
      bypass grafting with radial artery harvesting were assessed using a questionnaire
      at 3 and 12 months after surgery. The questionnaire contained 9 statements
      concerning hand and forearm problems in daily life. The answers were graded in 7
      levels. An answer of higher than grade 3 (mild symptoms) was regarded as a
      significant symptom. No hand ischemic complications was observed. In the 12 month
      study, 152 patients (98.1%) were normal. Hand pain and numbness occurred in 25
      patients (16.1 %) and 33 patients (21.3%), respectively, at 3 months and were
      markedly improved at 12 months (pain: 13 (8.4%), p = 0.045, numbness: 20 (12.9%),
      p = 0.069). Total scores for all questions also significantly decreased at 12
      months (10.2 +/- 3.5) compared with 3 months (11.1 +/- 3.9) postoperatively (mean
      +/- SD, p = 0.0003). Radial artery harvest was quite acceptable from the
      patient's perception, although a few patients had numbness and pain in the 3
      months after surgery. Those complications significantly improve in the later
      postoperative phase.

PMID- 12224819
TI  - CD36 genotype and long-chain fatty acid uptake in the heart.
AB  - Homozygous or compound heterozygous mutation of the CD36 gene (CD36-/-) in humans
      results in severe defects of the uptake of long-chain fatty acids (LCFAs) in the
      heart. Because the effect of a single mutation of this gene (CD36+/-) on the LCFA
      uptake is not known, it was evaluated in 29 subjects with the CD36 wild-type gene
      (WT) (6 healthy subjects, 10 patients with heart disease), CD36+/- (4 healthy
      subjects, 5 patients) and CD36-/- (4 patients). The CD36 genotype was identified
      in the coding region of genomic DNA, and the expression of CD36 protein was
      examined by flow cytometry after staining with monoclonal anti-CD36 antibody. The
      LCFA uptake in the heart was assessed as the radioactivity accumulation ratio of
      heart to mediastinum after intravenous administration of iodine-123 15-(p
      iodophenyl)-3-R, S-methylpentadecanoic acid (H/M ratio). The H/M ratios in WT,
      CD36+/- and CD36-/- were 2.28 +/- 0.10, 1.90 +/- 0.06 and 1.40 +/- 0.11,
      respectively (p < 0.0001, among groups). The H/M ratio between healthy subjects
      and patients with heart disease for WT and CD36+/- did not differ significantly
      (ie, those of WT and CD36+/- in healthy subjects and patients were 2.29 +/- 0.08
      vs 2.27 +/- 0.12 and 1.90+/- 0.07 vs 1.89 +/- 0.05, respectively). Not only CD36
      /- but also CD36+/- resulted in a significant reduction of the LCFA uptake in the
      heart independent of heart disease, suggesting genotype dependency and that CD36
      might be a fundamental determinant of myocardial LCFA uptake.

PMID- 12224820
TI  - Intracoronary administration of a thromboxane A2 synthase inhibitor relieves
      acetylcholine-induced coronary spasm.
AB  - This study sought to clarify the effectiveness of intracoronary administration of
      a thromboxane (TX) A2 synthase inhibitor, Ozagrel Na, to relieve coronary spasms
      induced by intracoronary injection of acetylcholine (ACh). An ACh spasm
      provocation test was performed in 92 consecutive patients with coronary spastic
      angina using incremental doses of 20, 50, and 80 microg into the right coronary
      artery, and 20, 50, and 100 microg into the left coronary artery within 20s. A
      coronary spasm was defined as TIMI 0 or 1 flow and an intracoronary injection of
      20 mg Ozagrel Na was administered when it was provoked. Within 2 min of the
      administration of the TXA2 synthase inhibitor, ACh-induced coronary spasms were
      relieved (TIMI 3 flow) in 88.1% of procedures without complications. In only 4
      cases (4.3%), it took more than 3 min to relieve the coronary spasms.
      Intracoronary administration of 20mg Ozagrel Na when ACh-induced spasms occurred,
      shortened the spasm relief time in all 7 patients (200 +/- 59s vs 111 +/- 23s, p
      < 0.01), improved the maximal ST segment elevation in 5 of them (3.9 +/- 3.7 mm
      vs 0.7 +/- 1.5 mm, p < 0.05), and stopped chest pain in 4 patients. In 4 patients
      who had ACh-induced coronary spasm of the left anterior descending artery, the
      TXB2 concentration in the coronary sinus decreased after intracoronary
      administration of Ozagrel Na into the left coronary artery (463 +/- 562 vs 96 +/-
      45, p < 0.01). In conclusion, intracoronary administration of a TXA2 synthase
      inhibitor can relieve ACh-induced coronary spasms by inhibiting TXA2 synthesis in
      the local coronary circulation.

PMID- 12224821
TI  - Noninvasive differentiation of normal from pseudonormal/restrictive mitral flow
      using TEI index combining systolic and diastolic function.
AB  - Differentiation of normal from pseudonorma/restrictive mitral flow is not
      necessarily easy. Pseudonormal/restrictive flow is usually associated with left
      ventricular (LV) dysfunction, which can be detected using the TEI index,
      combining systolic and diastolic function. The purpose of this study was to test
      the feasibility of using the TEI index to differentiate pseudonormal/restrictive
      from normal mitral flow. In 33 patients with mitral flow E/A > or = 1 and LV mid
      diastolic pressure measured by catheterization, the LV volumes, mitral E and A
      velocity, deceleration time of the E velocity, and the TEI index, defined as the
      sum of the isovolumic contraction and relaxation time divided by ejection time,
      were evaluated using Doppler echocardiography. Pseudonormal/restrictive mitral
      flow was defined as mitral flow E/A > or = 1 associated with LV mid-diastolic
      pressure > 12 mmHg. There were 22 and 11 patients with normal and
      pseudonorma/restrictive mitral flow, respectively. Among the indices of LV
      function, the TEI index achieved the best correlation with LV mid-diastolic
      pressures (r2 = 0.63, p < 0.0001). By setting the TEI index > or = 0.65 as the
      criteria for pseudonormal/restrictive mitral flow, this diagnosis had
      sensitivity, specificity, and accuracy of 82%, 96%, and 91%, respectively. TEI
      index allows noninvasive differentiation of pseudonormal /restrictive from normal
      mitral flow.

PMID- 12224822
TI  - Coexistence of impairment of endothelium-derived nitric oxide and platelet
      derived nitric oxide in patients with coronary risk factors.
AB  - Impairment of endothelium-derived nitric oxide (EDNO) has been demonstrated in
      patients with coronary risk factors in some studies, as well as impaired platelet
      derived nitric oxide (PDNO) in other studies. However, no study has examined
      whether these impairments coexist. In 24 patients with coronary risk factors,
      femoral vascular endothelial function was assessed with acetylcholine (ACh: 50,
      100, 200 and 400 microg/min) and endothelium-independent vascular function with
      nitroglycerin (NTG; 50, 100, 200 microg/min) using a Doppler flow-wire technique,
      as well as ADP (5 micromol/L)-induced PDNO release with an NO-specific electrode.
      The ACh-mediated percent change in femoral vascular resistance index (% change of
      FVRI) and PDNO release had a significant correlation with the number of risk
      factors. The ACh-mediated % change of FVRI, but not that with NTG, significantly
      correlated with the PDNO release. Both EDNO and PDNO bioactivities are impaired
      in patients with coronary risk factors and there is a common mechanism.

PMID- 12224823
TI  - Acute effect of endothelin AB antagonist on sympathetic outflow in conscious rats
      with heart failure.
AB  - Although ET-1 antagonists have been beneficial in the treatment of heart failure
      (HF), their involvement in the effect on the sympathetic nervous system in HF
      remains unknown. The present study investigated the role of endogenous endothelin
      (ET) in the sympathetic nervous system in HF by observing the effect of ET AB
      antagonist (TAK-044) on renal sympathetic nerve activity (RSNA) in conscious rats
      with HF (n = 7). HF was induced by left coronary artery ligation and 6 weeks
      later, TAK-044 was intravenously administered in the conscious and freely moving
      rats. RSNA, mean arterial pressure (MAP) and heart rate were compared with rats
      with sham operations (sham; n = 7). MAP was significantly decreased in both
      groups; however, RSNA was significantly decreased only in the HF group at 5 min
      after administration, and this change continued until 10 min. There was also an
      effect of TAK-044 on the arterial baroreflex function indicated by the slope of
      RSNA to the changes in MAP during phenylephrine and nitroprusside injection in
      both groups. Compared with the sham group, the HF group showed impaired arterial
      baroreflex control of RSNA during phenylephrine injection, and intravenous
      administration of TAK-044 normalized this abnormality, whereas the function in
      the sham group was not changed. These data show that ET AB antagonist suppressed
      renal sympathetic activity in rats with HF, and improved arterial baroreflex
      function. The beneficial effect of endothelin antagonist on heart failure may
      involve improvement of the increased sympathoexcitation and impaired arterial
      baroreflex function in HF.

PMID- 12224824
TI  - L-cysteine prevents oxidation-induced block of the cardiac Na+ channel via
      interaction with heart-specific cysteinyl residues in the P-loop region.
AB  - The present study investigated the protective effects of L-cysteine on the
      oxidation-induced blockade of Na+ channel a-subunits, hH1 (cardiac) and hSkM1
      (skeletal), expressed in COS7 cells. Na+ currents were recorded by the whole-cell
      patch clamp technique (n = 3-7). L-cysteine alone blocked hH1 and hSkM1 in a dose
      dependent manner, with saturating L-cysteine block at 3,000 micromol/L. Hg2+, a
      potent sulfhydryl oxidizing agent, blocked hH1 with a time to 50% inhibition
      (Time50%) of 20s. Preperfusion of COS7 cells with 100 micromol/L L-cysteine
      significantly slowed the Hg2+ block of hH1 (Time50% = 179 s). L-cysteine did not
      prevent Hg2+ block of hSkM1 (Time50% = 37s) or the C373Y hH1 mutant (Time50% =
      43s). As for other sulfo-amino acids, homocysteine prevented the Hg2+ block of
      hH1, with the Time50% (70s) being significantly smaller than that of L-cysteine,
      whereas methionine did not prevent the Hg2+ block of hH1. L-cysteine did not
      prevent the Cd2+ block of hH1. These results indicate that L-cysteine selectively
      acts on heart-specific Cys373 in the P-loop region of hH1 to prevent Cys373 from
      the oxidation-induced sulfur-Hg-sulfur bridge formation.

PMID- 12224825
TI  - Overexpression of endothelial nitric oxide synthase attenuates cardiac
      hypertrophy induced by chronic isoproterenol infusion.
AB  - Endogenous nitric oxide (NO) inhibits the contractile response to beta-adrenergic
      stimulation, but its effect on cardiac hypertrophy mediated by beta-adrenoceptors
      remains unclear. The present study was designed to determine whether
      overproduction of endothelial NO synthase (eNOS) could inhibit cardiac
      hypertrophy induced by chronic isoproterenol (ISO) infusion (30mg/kg per day)
      using eNOS overexpressing (eNOS-Tg) mice and wild-type (WT) mice. In a separate
      group, WT mice were treated with ISO and hydralazine to decrease blood pressure
      to the same levels in eNOS-Tg mice. The eNOS expression, NOS activity, and cGMP
      levels in the heart were remarkably higher in eNOS-Tg mice than in WT mice. ISO
      increased both heart weight and the heart/body weight ratio, which were
      significantly attenuated in eNOS-Tg mice compared with WT or hydralazine-treated
      WT mice. Histological examination revealed that the extent of fibrosis was not
      significantly different among the 3 groups, and that the increase in myocyte size
      was more than 10% lower in eNOS-Tg than in the other groups. In addition, up
      regulated expression of atrial natriuretic peptide mRNA associated with cardiac
      hypertrophy was significantly inhibited in eNOS-Tg mice during ISO infusion.
      These results indicate that endogenous NO might act as a negative modulator for
      the hypertrophic response to beta-adrenergic stimulation.

PMID- 12224826
TI  - Effects of disopyramide and mexiletine on the terminal repolarization process of
      the in situ heart assessed using the halothane-anesthetized in vivo canine model.
AB  - This study was designed to assess the effects of typical class I drugs on the
      terminal repolarization process of the in situ heart, which is a useful marker of
      the potential of drug-induced long QT syndrome. Disopyramide (0.3 and 3.0 mg/kg
      per 10 min, n = 6) or mexiletine (0.3 and 3.0 mg/kg per 30s, n = 6) was
      intravenously administered to halothane-anesthetized beagle dogs under the
      monitoring of multiple cardiovascular parameters. Antiarrhythmic concentrations
      were obtained with the high dose of each drug. The low dose of disopyramide or
      mexiletine hardly affected any of the electrophysiological parameters assessed.
      The high dose of disopyramide prolonged the monophasic action potential duration
      (MAP90) and effective refractory period (ERP) to a similar extent, thus
      displacing the terminal repolarization period backward, which might provide a
      potential proarrhythmic substrate, particularly at a slow heart rate. On the
      other hand, the high dose of mexiletine shortened the MAP90, but prolonged the
      ERP, resulting in the disappearance of the terminal repolarization period, which
      could prevent premature excitation with its associated conduction slowing. These
      electrophysiological effects of disopyramide and mexiletine on the terminal
      repolarization phase may at least in part explain their clinically described
      antiarrhythmic and proarrhythmic properties.

PMID- 12224827
TI  - Peripartum cardiomyopathy and biventricular thrombi.
AB  - Peripartum cardiomyopathy is a rare cardiac disorder characterized by the
      development of heart failure in the last month of pregnancy or up to 5 months
      postpartum in women without other determinable causes of cardiac failure.
      Intracardiac thrombi have been found at autopsy in some patients with this
      condition and have been demonstrated in the left or right ventricles on 2
      dimensional echocardiography. A 23-year-old woman presented with peripartum
      cardiomyopathy and biventricular thrombi on echocardiography. The thrombi were
      spherical, pedunculate, shaggy and irregular in configuration, and freely mobile,
      suggesting that they were fresh. She was treated with conventional heart failure
      therapy and anticoagulants. Four days later, the apical thrombi within both
      ventricles had disappeared and there was no evidence of embolism on physical
      examination. The hypercoagulable state of the peripartum period and the severe
      biventricular dysfunction most likely led to the formation of biventricular
      thrombi.

PMID- 12224828
TI  - Neurally mediated syncope manifesting during atrial fibrillation: a case report.
AB  - A 64-year-old male was admitted to hospital because of repeated episodes of
      syncope and palpitation. Ambulatory monitoring revealed paroxysmal atrial
      fibrillation (AF) as the cause of palpitation; he did not have structural heart
      disease. The induction of AF by rapid pacing (50 Hz for 1 s) in an upright
      position provoked syncope with a vasodepressor response. Atropine sulfate blocked
      the induction of syncope. The possible etiology was neurally mediated syncope
      that manifested only during AF, which suggests that the abnormal vagal activity
      during AF in this case exaggerated the vasodepessor response while upright.

PMID- 12224829
TI  - Two cases of a free-floating ball thrombus in the left atrium.
AB  - A free-floating ball thrombus in the left atrium is an unusual occurrence that
      may cause fatal systemic emboli or left ventricular inflow obstruction, often
      resulting in sudden death. The first of 2 cases was a 59-year-old female with
      mitral stenosis and chronic atrial fibrillation who presented with severe
      dyspnea. Transthoracic echocardiography revealed a free-floating ball thrombus
      and emergency thrombectomy and mitral valve replacement were performed
      successfully. A second thrombus, which was not found at preoperative examination,
      was attached to the anterior mitral leaflet and may have been the source of the
      free-floating ball thrombus. The second case was a 79-year-old female with
      chronic renal failure who underwent mitral valve replacement 11 years prior to
      admission. She had been dependent on hemodialysis for 10 years, and had suffered
      several recent transient cerebral ischemic attacks. Computed tomography showed a
      ring-shaped, high-density area in the left atrium and transthoracic
      echocardiography revealed a floating ball thrombus in the left atrium.
      Thrombectomy was performed, but the patient died as a result of postoperative
      pneumonia 2 months later. Case 2 appears to be the first reported case of a ball
      thrombus in a hemodialysis patient who had previously undergone mitral valve
      replacement.

PMID- 12224830
TI  - Rupture of the anterolateral papillary muscle caused by a single diagonal branch
      obstruction.
AB  - This report presents the first case of anterolateral papillary muscle rupture
      caused by a diagonal branch occlusion only. Although the patient was in shock on
      admission, he was successfully treated by emergency surgery after hemodynamic
      stabilization by a percutaneous cardiopulmonary support system. This case implies
      that the anterolateral papillary muscle has a single blood supply and that it can
      rupture by an occlusion of only one diagonal branch even after balloon
      angioplasty.

PMID- 12224831
TI  - Rate-dependent changes in atrial action potential duration after short- duration
      rapid atrial pacing in humans.
AB  - The effect of rapid atrial pacing on the rate adaptation of the atrial action
      potential duration was studied in humans. The right atrial monophasic action
      potential (RAMAP) of 5 patients was recorded before and after 30 min of rapid
      atrial pacing. The pacing cycle length (CL) was 146 +/- 9 ms, the shortest
      duration at which 1:1 capture was possible. The RAMAP duration at 90%
      repolarization (RMAPD) was measured. CL-dependent changes in RAMAPD (CL 600 ms-CL
      300 ms) before and after rapid atrial pacing were 51.8 +/- 10.7 ms and 30.8 +/-
      7.6 ms (p < 0.05), respectively.

PMID- 12224832
TI  - Big elephants fighting whilst children's policy misses out?

PMID- 12224833
TI  - Reduction of chronic sorrow: a health promotion role for children's community
      nurses?
AB  - Families who have a child with a chronic illness face losses in their lives and
      react in a variety of ways. The theory of constuctivism is used to examine these
      losses. The ongoing nature of these losses can lead to ongoing grief rather than
      acceptance. This is discussed within the themes of time-limited grief and chronic
      sorrow. The role of children's community nurses in assisting families with
      resolving this sorrow is discussed, the main suggestions being the provision of
      an empathetic presence, time and the provision of accurate and specific
      information regarding the illness and the ways of managing it within the familys
      life.

PMID- 12224834
TI  - 'Kiss, cuddle, squeeze': the experiences and meaning of touch among parents of
      children with autism attending a Touch Therapy Programme.
AB  - The aim of this qualitative study was to explore the experiences and meaning of
      touch between parents and children with autism before and after attending a Touch
      Therapy Programme. The sample comprised 12 parents (1 father and 11 mothers) of
      children (1 female and 11 male) with autism. Parents were interviewed before and
      immediately after the 8-week programme. Pre-programme results suggested that
      children were controlling the experience of touch. Parents felt 'hurt' in
      response to the 'aloof nature of autism, and natural parenting instincts (e.g.
      spontaneous cuddles) were restricted. Post-programme results suggested that
      children appeared to tolerate touch. Parents reported that routine tasks (e.g.
      dressing) were accomplished more easily and that children appeared generally more
      relaxed. Parents reported feeling 'closer' to their children and felt that the
      touch therapy had opened a communication channel between themselves and their
      children.

PMID- 12224835
TI  - Exploitation of children and young people through prostitution.
AB  - The numbers of children in contemporary society involved in prostitution is still
      largely unknown. However, there are multiple factors which leave children
      vulnerable and involved in prostitution. This article aims to explore the
      historical context of child prostitution, factors which may predispose an
      adolescent engaging in prostitution, and the role that professionals within the
      healthcare settings can offer.

PMID- 12224836
TI  - Death education: what should student children's nurses be taught?
AB  - Children's nursing has developed rapidly over the last 50 years and continues to
      be a dynamic process. In many respects children's nursing educators, together
      with their practice colleagues, have been central to these developments. There is
      concordance that all children have the right to the highest standards of care and
      this especially applies to the small numbers who die; however, the management of
      dying children continues to challenge all involved. The reasons for this may
      relate in part to deficiencies in death education for student children's nurses.
      This paper reports on a qualitative study that explored delivery of death
      education by a small number of UK children's nursing lecturers. The results and
      recommendations presented here may help to inform death education, and ultimately
      help to facilitate high-quality care for dying and bereaved children and their
      families.

PMID- 12224837
TI  - Description of breastfeeding practices among poorer sections in Calcutta
      Metropolitan Area and its impact on postpartum infecundity.
AB  - Descriptions of breastfeeding practices among residents in slum areas of Kolkata
      and the influence of breastfeeding on postpartum amenorrhoea is the focus of this
      study. Three out of four women initiate breastfeeding after one hour of birth and
      three out of five women squeeze the first milk from the breast before
      breastfeeding. Though the median duration of breastfeeding is long, the duration
      of exclusive breastfeeding is much shorter. Breastfeeding during the first six
      months has a significant negative influence on the rate of return to menses.

PMID- 12224838
TI  - Pubertal changes in daytime sleepiness. 1980.

PMID- 12224839
TI  - Regulation of sleepiness in adolescents: update, insights, and speculation.

PMID- 12224840
TI  - Ketamine and MK-801 decrease acetylcholine release in the pontine reticular
      formation, slow breathing, and disrupt sleep.
AB  - STUDY OBJECTIVES: Ketamine induces a dissociated state of consciousness by
      binding to the phencyclidine binding site within the ion channel gated by the N
      methyl-D-aspartate (NMDA) receptor. The brain regions and neurotransmitter
      systems mediating ketamine-induced alterations in arousal remain incompletely
      understood. This study used in vivo microdialysis to test the hypothesis that
      ketamine alters acetylcholine (ACh) release in the medial pontine reticular
      formation (mPRF). DESIGN: Acetylcholine (ACh) release, sleep, and breathing were
      quantified following systemic ketamine administration. Microdialysis was used to
      deliver the NMDA-channel blocker dizocilpine maleate (MK-801) and the R(-)-isomer
      of ketamine into the mPRF while measuring ACh release. SETTING: N/A.
      PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Systemically
      administered ketamine disrupted normal sleep-cycle organization, reduced mPRF ACh
      release, and significantly slowed rate of breathing. Dialysis delivery of MK-801
      to the mPRF significantly decreased respiratory rate and mPRF ACh release.
      Dialysis delivery to the mPRF of the R(-)-ketamine isomer significantly decreased
      mPRF ACh release. CONCLUSIONS: Decreased mPRF ACh release caused by systemically
      administered ketamine was mimicked by mPRF dialysis delivery of MK-801 and the R(
      )-ketamine isomer. These data are consistent with the conclusion that
      systemically administered ketamine may alter arousal and breathing, in part, by
      altering cholinergic neurotransmission in the mPRF.

PMID- 12224841
TI  - Medical and socio-professional impact of insomnia.
AB  - STUDY OBJECTIVES: Insomnia, a highly prevalent disorder with direct and indirect
      economic and professional consequences, affects daytime functioning, behavior,
      and quality of life. Several studies have shown that insomnia affects the
      workforce and is associated with an increased risk of accidents. Insomnia may
      also play a role in other disorders. Our study attempted to evaluate the socio
      professional correlates of insomnia by comparing a group of insomniacs to a group
      of good sleepers. DESIGN: With a questionnaire focused on the socio-professional
      and medical consequences of insomnia, we surveyed a group of severe insomniacs
      and a group of good sleepers. Persons with psychiatric disorders according to the
      DSM-IV minimum criteria for anxiety and depression were eliminated from each
      group. After screening, 240 insomniacs and 391 good sleepers remained and were
      then compared. MEASUREMENTS AND RESULTS: Compared to good sleepers, severe
      insomniacs reported more medical problems, had more physician-office visits, were
      hospitalized twice as often, and used more medication. Severe insomniacs had a
      higher rate of absenteeism, missing work twice as often as did good sleepers.
      They also had more problems at work (including decreased concentration,
      difficulty performing duties, and more work-related accidents). CONCLUSIONS: Our
      study showed that insomnia has socio-professional consequences and is correlated
      with lower medical status.

PMID- 12224842
TI  - NREM sleep EEG frequency spectral correlates of sleep complaints in primary
      insomnia subtypes.
AB  - STUDY OBJECTIVES: To determine whether the frequency spectrum of the sleep EEG is
      a physiologic correlate of 1) the degree to which individuals with persistent
      primary insomnia (PPI) underestimate their sleep time compared with the
      traditionally scored polysomnogram (PSG) and 2) the sleep complaints in PPI
      subjects who have relatively long traditionally scored PSG sleep times and
      relatively greater underestimation of sleep time. DESIGN: We compared EEG
      frequency spectra from REM and NREM sleep in PPI subjects subtyped as subjective
      insomnia sufferers (those with relatively long total sleep time and relative
      underestimation of sleep time compared with PSG), and objective insomnia
      sufferers (those with relatively short PSG total sleep time) with EEG frequency
      spectra in normals. We also studied the correlation between these indices and the
      degree of underestimation of sleep. Further, we determined the degree to which
      sleep EEG indexes related to sleep complaints. SETTING: Duke University Medical
      Center Sleep Laboratory. PARTICIPANTS: Normal (N=20), subjective insomnia (N=12),
      and objective insomnia (N=18) subjects. INTERVENTIONS: N/A. MEASUREMENTS AND
      RESULTS: Lower delta and greater alpha, sigma, and beta NREM EEG activity were
      found in the patients with subjective insomnia but not those with objective
      insomnia, compared with the normal subjects. These results were robust to changes
      in the subtyping criteria. No effects were found for REM spectral indexes. Less
      delta non- REM EEG activity predicted greater deviation between subjective and
      PSG estimates of sleep time across all subjects. For the subjective insomnia
      subjects, diminished low-frequency and elevated higher frequency non- REM EEG
      activity was associated with their sleep complaints. CONCLUSIONS: NREM EEG
      frequency spectral indexes appear to be physiologic correlates of sleep
      complaints in patients with subjective insomnia and may reflect heightened
      arousal during sleep.

PMID- 12224843
TI  - Sleepiness and sleep disorders in shift workers: a study on a group of italian
      police officers.
AB  - STUDY OBJECTIVES: evaluation of shift-work effect on sleepiness, sleep disorders,
      and sleep-related accidents in a population of police officers. DESIGN:
      Aquestionnaire-based survey was used to gather information on age and physical
      characteristics, working conditions, sleep problems, and accidents. Sleepiness
      was measured by the Epworth Sleepiness Scale (ESS) while the presence of sleep
      disorders was evaluated by a score (SDS) drawn from indicators of insomnia,
      breathing disorders, periodic limb movements and restless legs syndrome, and
      hypersomnia. The effects of age, gender, body mass index, working conditions, and
      seniority on ESS, SD score, and accidents were analyzed by linear and logistic
      regression. SETTING: The self-administered questionnaires were filled in by
      police officers in the district of Genoa (Italy). PARTICIPANTS: 1,280 police
      officers: 611 shift workers (SW) and 669 non-shift workers (NSW). INTERVENTIONS:
      N/A. MEASUREMENTS AND RESULTS: The ESS score was not higher in SW than in NSW,
      while the SDS was significantly influenced by shift-work conditions and seniority
      in shift work. The occurrence of sleep-ascribed accidents was significantly
      increased in the SW group and related to the presence of indicators of sleep
      disorders. There was evidence for sleep disorders in 35.7% of SW and in 26.3% of
      NSW. CONCLUSIONS: Shift-work conditions and seniority may enhance sleep disorders
      and may favor sleep-related accidents, but they do not influence ESS score.
      Stressful conditions could cause sleepiness to be underestimated, or else they
      might overcome sleepiness. However, our data should alert occupational health
      physicians for the diagnosis and prevention of possible undetected intrinsic
      sleep disorders, which could possibly worsen shift workers' health and increase
      the risk of accidents.

PMID- 12224844
TI  - Health-related quality of life and sleep-disordered breathing in children.
AB  - STUDY OBJECTIVES: To assess the extent to which sleep-disordered breathing (SDB)
      is associated with impairment of health-related quality of life (HRQOL) in
      children DESIGN: Observational study of pediatric participants in a longitudinal
      genetic-epidemiologic cohort study of SDB. SETTING: Community-based; studies
      conducted at participants' homes PARTICIPANTS: 298 children, aged 11.1 years +/-
      3.5 SD; 54% females; 61% African-American or Other; 81% with a family member
      identified with laboratory-confirmed SDB. INTERVENTIONS: Not applicable
      MEASUREMENTS AND RESULTS: The HRQOL was assessed with the Child Health
      Questionnaire (CHQ-PF50), a 50-item parent-completed form that measures 14
      multidimensional health concepts. Sleep-disordered breathing (SDB) was assessed
      with ovemight in-home monitoring that recorded nasal-oral airflow, pulse
      oximetry, chest-wall impedance, and heart rate. Using logistic regression
      analyses, each CHQ scale outcome was analyzed independently for the effect of
      SDB, adjusting for other potential confounding variables and for family
      correlated data. Significant differences in overall physical health and
      complaints of bodily pain were observed in children with generally mild levels of
      SDB. Relationships persisted after adjustment for age, gender, ethnicity,
      obesity, and asthma. CONCLUSIONS: SDB in children is associated with measurably
      lower levels of specific dimensions of HRQOL in children. Decrements in HRQOL are
      measurable even for children with mild SDB, with increasing effects observed with
      more severe SDB.

PMID- 12224845
TI  - Epileptic nocturnal wanderings with a temporal lobe origin: a stereo
      electroencephalographic study.
AB  - To show the results of the exploration conducted with intracerebral electrodes in
      a patients affected by epileptic nocturnal wanderings (ENWs). METHOD: The patient
      was investigated with long-term video-stereo-electroencephalographic (SEEG)
      monitoring by means of stereotactically introduced intracerebral electrodes.
      RESULTS: We recorded four nocturnal seizures with typical features of ENWs. The
      SEEG ictal recordings demonstrated a well-localized initial discharge always
      confined to the right temporal structures with secondary spread to the cingulate
      regions. DISCUSSION: Together with paroxysmal arousals and nocturnal paroxysmal
      dystonia, ENWs has been considered as a manifestation of the nocturnal frontal
      lobe epilepsy. Our investigation and the result of surgical outcome in this
      patient indicate that in some cases such episodes could have a temporal-lobe
      origin.

PMID- 12224846
TI  - Excessive daytime somnolence and increased rapid eye movement pressure in
      myotonic dystrophy.
AB  - STUDY OBJECTIVES: Sleep studies at Duke University Medical Center were
      retrospectively reviewed to investigate causes of excessive daytime sleepiness
      (EDS) in our myotonic dystrophy1 (DM1) patient population, identified by an
      abnormal CTG expansion on chromosome 19. Excessive daytime sleepiness, an
      accentuated desire for sleep or the occurrence of sleep episodes that interfere
      with normal wakefulness, is common in patients with DM1. Sleep abnormalities,
      such as central and obstructive sleep apnea, have been extensively reported;
      however, many DM1 patients suffer from EDS in the absence of any identified
      respiratory dysrhythmia. DESIGN: Nineteen DM1 patients, with the clinical
      diagnosis and genetic confirmation in the proband or a related family member, had
      a sleep evaluation. Polysomnogram (PSG) and mean sleep latency test (MSLT)
      results were retrospectively reviewed. SETTING: N/A. PARTICIPANTS: N/A.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Most DM1 patients demonstrated
      grade 3 (distal weakness) or grade 4 (mild to moderate proximal weakness) on the
      myotonic dystrophy impairment rating scale. All patents had a PSG, with 13
      patients having an MSLT the following day. Clinically significant respiratory
      abnormalities on PSG, defined in this study as a respiratory disturbance index >
      15 and/or upper airway resistance syndrome, could not explain the EDS observed in
      14 of 19 patients. Decreased mean sleep latency was observed in 12 of 13 patients
      evaluated by MSLT, while sleep onset REM sleep was seen in 8 of 13 patients.
      Pathologic REM onset (2 or more SOREMs on MSLT) was seen in 5 of 13 patients,
      with 3 of those 5 patients having a PSG with RDI < or = 5. CONCLUSIONS: Most DM1
      patients did not have significant respiratory abnormalities on PSG to explain the
      manifested EDS. Objective sleepiness is common in DM1, and pathologic REM
      pressure can be commonly observed. These observations imply an intrinsic
      hypersomnolence sometimes accompanied by abnormal REM pressure may be an integral
      part of EDS in DM1 patients.

PMID- 12224847
TI  - The effects of mirtazapine on sleep: a placebo controlled, double-blind study in
      young healthy volunteers.
AB  - STUDY OBJECTIVES: Mirtazapine is classified as a noradrenergic and specific
      serotonergic antidepressant. This study aims at objectively investigating the
      effects of single-dose mirtazapine on sleep of healthy volunteers. DESIGN AND
      SETTING: We studied the effect of acute administration of mirtazapine (30 mg) on
      the sleep polysomnogram, using a double-blind, placebo-controlled design.
      Subjects spent 3 consecutive nights in the laboratory. First night allowed for
      adaptation to the laboratory and application of electroencephalogram electrodes,
      while the second and third nights were reserved for recording baseline sleep and
      studying the effects of drug treatment, respectively. PARTICIPANTS: Young healthy
      volunteers (n=20), with a mean age of 24 years, were randomly separated into two
      groups: placebo (n=10) and mirtazapine (n=10). INTERVENTIONS: On the third night,
      subjects received either placebo or mirtazapine. Comparisons were made between
      sleep variables from baseline values in both groups. Independent samples t-test
      was utilized to evaluate the differences between the two groups. MEASUREMENT AND
      RESULTS: Mirtazapine improved the variables related to sleep continuity when
      compared with placebo. It increased the sleep efficiency index, while decreasing
      the number of awakenings and their duration. The slow wave sleep time was
      increased, while the stage 1 sleep time was decreased significantly. There was no
      significant effect on rapid eye movement sleep variables. CONCLUSION: Our
      findings suggest that mirtazapine has considerable effects on slow wave sleep.
      Further studies are recommended to investigate the efficiency of antidepressants,
      in respect to the effects of 5-HT2 blockade on slow wave sleep.

PMID- 12224848
TI  - Movement during sleep: associations with posttraumatic stress disorder,
      nightmares, and comorbid panic disorder.
AB  - STUDY OBJECTIVES: To corroborate findings from the National Comorbidy study with
      objective sleep data. DESIGN: Retrospective data review. SETTING: Sleep
      Laboratory, National Center for Posttraumatic Stress Disorder PARTICIPANTS: Male
      Vietnam combat veteran. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: We
      reanalyzed laboratory sleep data obtained from subjects undergoing inpatient
      treatment for posttraumatic stress disorder. Comorbid panic disorder was not
      associated with a significant worsening of objective sleep in this sample.
      Posttraumatic stress disorder, comorbid panic disorder, and trauma-related
      nightmare complaint were all associated with significant and systematic
      reductions of sleep movement time. Analyses of potential "rescoring" artifacts
      provided further support for this effect. CONCLUSIONS: A curvilinear function may
      describe the relationship between anxiety symptom severity and sleep-movement
      time in both posttraumatic stress disorder and panic disorder. Evidence for
      movement suppression in association with pathologic levels of human anxiety is
      consistent with the suppression of movement ("freezing") exhibited by animals
      under conditions of perceived threat.

PMID- 12224850
TI  - Use of routine ventrodorsal radiographic views of the pelvis to assess
      inclination of the wings of the sacrum in dogs.
AB  - OBJECTIVE: To determine the ratio of ventral-to-dorsal transverse diameters
      between the wings of the sacrum on ventrodorsal radiographic views of the pelvis
      in large dogs and to validate the reliability of this morphometric analysis for
      functional interpretation. SAMPLE POPULATION: Pelvic specimens from 40 large
      breed dogs and radiographs of 113 large-breed dogs. PROCEDURE: In an anatomic and
      radiographic evaluation, the transverse dorsal diameter (TVDS) and transverse
      ventral diameter (TVV) between the wings of the sacrum were evaluated in sacrum
      specimens and on corresponding radiographs of the pelvis and sacrum. The ratio
      between TVV and TVDS (VD ratio) was calculated. Intraobserver reliability was
      determined by calculation of the coefficient of variation. In a retrospective
      radiographic evaluation, the VD ratio was determined in Rottweilers, Golden
      Retrievers, and German Shepherd Dogs. Correlations between VD ratio and breed,
      age, and sex were tested. RESULTS: The VD ratio was significantly higher in
      Rottweilers than in Golden Retrievers and German Shepherd Dogs, denoting an
      oblique alignment of the sacral wings in Rottweilers (ie, the dorsal aspects of
      the sacral wings were located more medially than the ventral aspects) and an
      almost sagittal alignment in the other breeds. The VD ratio was significantly
      associated with age but not with sex. CONCLUSIONS AND CLINICAL RELEVANCE:
      Sagittal alignment of the wings of the sacrum is considered to be biomechanically
      less efficient. These results provide a basis for further studies to evaluate
      radiographic assessment of the sacroiliac joints similar to the evaluation for
      hip dysplasia.

PMID- 12224849
TI  - Telemetric recording of sleep and home cage activity in mice.
AB  - STUDY OBJECTIVES: This study assessed differences in spontaneous sleep and
      locomotor activity in inbred and hybrid mouse strains and evaluated telemetry for
      recording sleep in mice. DESIGN: Uninterrupted recordings of sleep and home cage
      activity were obtained in four mouse strains. Pre-operative and post-operative
      home cage activity was obtained in two strains. SETTINGS: N/A PARTICIPANTS: The
      subjects were mice of three inbred (C57BL/6J (B6), n=25; BALB/cJ (C), n=24;
      DBA/2J (D2), n=30) strains and one hybrid (CB6F1/J (CB6: C x B6), n=19) strain.
      INTERVENTIONS: Electroencephalogram (EEG) and activity were recorded by
      telemetry, and behavioral states were visually scored based on EEG and activity
      records. Home cage activity was determined utilizing photobeam interruptions.
      MEASUREMENTS AND RESULTS: 1) Among the three inbred strains: C mice had the least
      sleep and the greatest amount of activity; D2 mice exhibited the least non-rapid
      eye-movement (NREM) sleep, the longest average NREM-bout length, and the greatest
      diurnal ratio of sleep and were the most inactive; B6 mice had the most sleep and
      an intermediate activity level; no differences among inbred strains were observed
      in total REM. The CB6 mice exhibited intermediate levels of total sleep and
      activity and had greater amounts of REM compared to its parental strains. 2)
      Total operative mortality was 9.3%, with all deaths occurring within 3 to 9 days
      after the operation; significant reductions in activity were observed after the
      operation. CONCLUSION: Differences in spontaneous sleep and activity exist among
      inbred and hybrid mouse strains. Accurate determination of sleep states in mice
      can be achieved with telemetrically recorded EEG and activity.

PMID- 12224851
TI  - Laparoscopic-assisted cystopexy in dogs.
AB  - OBJECTIVE: To develop a laparoscopic-assisted technique for cystopexy in dogs.
      ANIMALS: 8 healthy male dogs, 7 healthy female dogs, and 3 client-owned dogs with
      retroflexion of the urinary bladder secondary to perineal herniation. PROCEDURES:
      Dogs were anesthetized, and positive pressure ventilation was provided. In the
      healthy male dogs, the serosal surface of the bladder was sutured to the
      abdominal wall. In the healthy female dogs, the serosa and muscular layer of the
      bladder were incised and sutured to the aponeurosis of the external and internal
      abdominal oblique muscles. Dogs were monitored daily for 30 days after surgery.
      RESULTS: All dogs recovered rapidly after surgery and voided normally. In the
      female dogs, results of urodynamic (leak point pressure and urethral pressure
      profilometry) and contrast radiographic studies performed 30 days after surgery
      were similar to results obtained before surgery. Cystopexy was successful in all
      3 client-owned dogs, but 1 of these dogs was subsequently euthanatized because of
      leakage from a colopexy performed at the same time as the cystopexy. CONCLUSIONS
      AND CLINICAL RELEVANCE: The laparoscopic-assisted cystopexy technique was quick,
      easy to perform, and not associated with urinary tract infection or abnormalities
      of urination.

PMID- 12224852
TI  - Safety and efficacy of a technique for thoracoscopically guided pulmonary wedge
      resection in horses.
AB  - OBJECTIVE: To evaluate the safety and efficacy of thoracoscopically guided
      pulmonary wedge resection in horses. ANIMALS: 10 horses (5 control horses and 5
      horses affected with recurrent airway obstruction [ie, heaves]). PROCEDURE: Each
      horse underwent a thoracoscopically guided pulmonary wedge resection. Before,
      during, and after surgery, heart rate, respiratory rate, arterial blood gases,
      and systemic and pulmonary arterial pressures were measured. Physical
      examination, CBC, and thoracic radiography and ultrasonography were performed 24
      hours before and 2 and 48 hours after surgery. Pulmonary specimens were assessed
      by histologic examination. A second thoracoscopic procedure 14 days later was
      used to evaluate the resection site. RESULTS: The technique provided excellent
      specimens for histologic evaluation of the lung. Heart and respiratory rates
      decreased significantly after horses were administered sedatives. A significant
      transient decrease in Pao2 was detected immediately after pulmonary wedge
      resection, but we did not detect significant effects on arterial pH, Paco2, or
      mean arterial and pulmonary arterial pressures. All horses except 1 were
      clinically normal after thoracoscopic surgery; that horse developed hemothorax
      attributable to iatrogenic injury to the diaphragm. The second thoracoscopy
      revealed minimal inflammation, and there were no adhesions. CONCLUSIONS AND
      CLINICAL RELEVANCE: Thoracoscopically guided pulmonary wedge resection provides a
      minimally invasive method for use in obtaining specimens of lung tissues from
      healthy horses and those with lung disease. This technique may be useful for the
      diagnosis of diseases of the lungs and thoracic cavity.

PMID- 12224854
TI  - Comparison of corn gluten meal and meat meal as a protein source in dry foods
      formulated for cats.
AB  - OBJECTIVE: To compare the nutritional value of corn gluten meal (CGM) and meat
      meal (MM) as a dietary source of protein in dry food formulated for adult cats.
      ANIMALS: 8 healthy adult cats (4 males and 4 females). PROCEDURE: Diets
      containing CGM or MM as the main protein source were each fed for a 3-week period
      in a crossover study. Digestibility and nutritional balance experiments were
      conducted during the last 7 days of each period. Furthermore, freshly voided
      urine was obtained to measure urinary pH, struvite crystals, and sediment
      concentrations. RESULTS: Daily food intake and dry-matter digestibility were
      significantly higher for the MM diet. Fecal moisture content also was higher for
      the MM diet. Apparent nitrogen (N) absorption and N retention were higher for the
      MM diet, even when values were expressed as a percentage to account for
      differences in N intake. Urinary pH, struvite activity product, number of
      struvite crystals in urine, and urinary sediment concentrations were not
      different between diets. Retention of calcium, phosphorus, and magnesium was
      lower for the CGM diet, and cats lost body calcium and magnesium when fed the CGM
      diet. CONCLUSIONS AND CLINICAL RELEVANCE: Meat meal was superior to CGM as a
      protein source in dry foods formulated for cats, because dry-matter digestibility
      and N utilization were higher for the MM diet. In addition, net loss of body
      calcium and magnesium for the CGM diet suggests that mineral requirements
      increase when CGM is used as a protein source.

PMID- 12224853
TI  - Cardiovascular effects of a high dose of romifidine in propofol-anesthetized
      cats.
AB  - OBJECTIVE: To determine the hemodynamic effects of IM administration of
      romifidine hydrochloride in propofol-anesthetized cats. ANIMALS: 15 adult
      domestic shorthair cats. PROCEDURE: Cats were randomly assigned to receive
      romifidine (0, 400, or 2,000 microg/kg, IM). Cats were anesthetized with propofol
      and mechanically ventilated with oxygen. The right jugular vein, left carotid
      artery, and right femoral artery and vein were surgically isolated and
      catheterized. Heart rate; duration of the PR, QRS, and QT intervals; mean
      pulmonary artery pressure; mean right atrial pressure; systolic, diastolic, and
      mean arterial pressures; left ventricular systolic pressure; left ventricular end
      diastolic pressure; and cardiac output were monitored. Systemic vascular
      resistance, rate of change of left ventricular pressure, and rate pressure
      product were calculated. Arterial and venous blood samples were collected
      anaerobically for determination of pH and blood gas tensions (Po2 and Pco2).
      RESULTS: Administration of romifidine at 400 and 2,000 microg/kg, IM, decreased
      heart rate, cardiac output, rate of change of left ventricular pressure, rate
      pressure product, and pH. Arterial and pulmonary artery pressures, left
      ventricular pressure, left ventricular end-diastolic pressure, and right atrial
      pressure increased and then gradually returned to baseline values. Arterial blood
      gas values did not change, whereas venous Pco2 increased and venous Po2
      decreased. Significant differences between low and high dosages were rare,
      suggesting that the dosages investigated produced maximal hemodynamic effects.
      CONCLUSIONS AND CLINICAL RELEVANCE: Romifidine produces cardiovascular effects
      that are similar to those of other alpha2-agonists. High dosages of romifidine
      should be used with caution in cats with cardiovascular compromise.

PMID- 12224855
TI  - Direct measurement of intracranial pressure in adult horses.
AB  - OBJECTIVE: To develop a method for surgical placement of a commercial microsensor
      intracranial pressure (ICP) transducer and to characterize normal ICP and
      cerebral perfusion pressures (CPP) in conscious adult horses. ANIMALS: 6 healthy
      castrated male adult horses (1 Holsteiner, 1 Quarter Horse, and 4 Thoroughbreds).
      PROCEDURE: Anesthesia was induced and maintained by use of isoflurane as the sole
      agent. Catheters were inserted percutaneously into the jugular vein and carotid
      artery. A microsensor ICP transducer was inserted in the subarachnoid space by
      means of right parietal craniotomy. The burr hole was then sealed with bone wax,
      the surgical incision was sutured, and the transducer was secured in place.
      Measurements were collected 1 hour after horses were able to stand during
      recovery from anesthesia. RESULTS: Mean +/- SD values for ICP and CPP were 2 +/-
      4 and 102 +/- 26 mm Hg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: This
      report describes a relatively facile technique for obtaining direct and accurate
      ICP measurements for adult horses. The ICP values obtained in this study are
      within reference ranges established for other species and provide a point of
      reference for the diagnosis of abnormal ICP in adult horses.

PMID- 12224856
TI  - Evaluation of an intron deletion in the c-kit gene of canine mast cell tumors.
AB  - OBJECTIVE: To evaluate molecular abnormalities in the c-kit gene of canine mast
      cell tumors (MCT) with different grades of cellular differentiation. SAMPLE
      POPULATION: 31 normal tissue specimens from dogs and 45 canine MCT classified
      according to grade of cell differentiation. PROCEDURES: Genomic DNA extractions
      were made from canine MCT and normal tissues. Parts of exon 11, intron 11, and
      exon 12 of the c-kit gene were amplified by use of polymerase chain reaction.
      These regions were cloned, sequenced, and compared with GenBank sequences of the
      National Center for Biotechnology International. A statistical analysis was used
      to compare sequences from canine MCT and normal tissues. RESULTS: A significantly
      higher percentage of homozygous intron 11 deletion was found in canine MCT (49%)
      than in normal tissues (13%). This percentage was also higher in moderately and
      poorly differentiated MCT, compared with well-differentiated MCT Although no
      mutations were detected in any of the specimens, a polymorphism at amino acid
      position 606 of the canine c-kit sequence was found in all the studied sequences.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated a relationship between
      intron 11 deletion and MCT and the grade of MCT differentiation. We suggest that
      intron 11 deletion may be implicated in the pathogenesis of MCT and could be used
      as a marker for diagnosis and prognosis of canine MCT.

PMID- 12224857
TI  - F-wave latency and F-wave conduction velocity for the tibial nerve in clinically
      normal dogs.
AB  - OBJECTIVE: To establish a method of F-wave examinations and to determine values
      of F-wave conduction velocity (FWCV) and F-wave latency for the tibial nerve of
      clinically normal dogs. ANIMALS: 21 clinically normal dogs. PROCEDURE: The F
      waves were elicited from the interosseous muscles via stimulation of the tibial
      nerve. The FWCV was determined by using the F-wave shortest value and the surface
      distance corresponding to the tibial nerve length. Correlation between the
      smallest latency value of the F-wave and the length of the tibial nerve and
      between the FWCV and rectal temperature were closely examined. RESULTS: F-wave
      latency was proportional to the length of the tibial nerve (correlation
      coefficient, 0.929). Mean +/- SD FWCV was 77.98 +/- 8.62 m/s. Regression equation
      was as follows: F-wave latency = 2.799 + (0.029 X length of the tibial nerve).
      The FWCV was increased when the measured rectal temperature was high. Correlation
      coefficient between FWCV and rectal temperature was 0.665. CONCLUSIONS AND
      CLINICAL RELEVANCE: In the study reported here, we established a reliable method
      for clinical evaluation of the F-wave. When assessing nerve conduction velocity,
      it is essential to measure nerve length along the pathway that the nerve impulse
      travels. This method of F-wave examination is a useful diagnostic tool for the
      evaluation of suspected dysfunction of the peripheral nervous system.

PMID- 12224858
TI  - Detection of Salmonella spp in fecal specimens by use of real-time polymerase
      chain reaction assay.
AB  - OBJECTIVE: To use real-time polymerase chain reaction (PCR) technology to develop
      a highly sensitive and specific diagnostic assay for the detection of Salmonella
      spp in fecal specimens. SAMPLE POPULATION: 299 fecal specimens from cattle,
      horses, and dogs. PROCEDURE: Enrichment of fecal specimens was followed by
      genomic DNA extraction by use of commercially available isolation kits. Real-time
      PCR assay was performed to target a Salmonella spp-specific DNA segment. Results
      of real-time PCR assay were compared with bacterial culture results to determine
      relative sensitivity and specificity. RESULTS: Use of the spaQ primer-probe set
      resulted in a relative sensitivity of 100% and a specificity of 98.2%, compared
      with bacterial culture results when tested on 299 clinical fecal specimens.
      CONCLUSIONS AND CLINICAL RELEVANCE: A rapid, sensitive, and specific assay for
      the detection of Salmonella spp from enriched clinical fecal specimens was
      developed. This technique would be highly valuable in clinical settings to help
      avoid or mitigate the complications arising from an outbreak of salmonellosis in
      a herd or among patients of a veterinary hospital.

PMID- 12224859
TI  - Effects of hydrocortisone on substrates of energy metabolism in alpacas.
AB  - OBJECTIVE: To evaluate effects of hydrocortisone administration, with and without
      concurrent administration of insulin, on intermediary metabolism in alpacas.
      ANIMALS: 8 adult castrated male alpacas. PROCEDURE: On each of 2 consecutive
      days, food was withheld from alpacas for 8 hours. Alpacas then were administered
      1 mg of hydrocortisone sodium succinate/kg, IV (time 0). On 1 of the days,
      randomly assigned alpacas were also administered regular insulin (0.2 U/kg, IV)
      120 minutes after hydrocortisone administration. Blood samples were collected at
      0, 120, 135, 150, 165, 180, 210, 240, 300, and 360 minutes. Plasma concentrations
      of glucose and lactate and serum concentrations of triglycerides, cholesterol,
      nonesterified fatty acids, and beta-hydroxybutyrate were determined. Data were
      compared between days. Additionally, serum insulin concentrations before and
      after hydrocortisone administration were determined for selected samples.
      RESULTS: Hydrocortisone administration induced hyperglycemia, hyperinsulinemia, a
      reduction in concentrations of triglycerides and cholesterol, and a reduction in
      triglyceride-to-cholesterol ratio. Subsequent insulin administration temporarily
      negated the hyperglycemic effects of hydrocortisone, induced temporary
      hyperlactemia, and augmented the reduction in blood triglycerides. CONCLUSIONS
      AND CLINICAL RELEVANCE: A single dose of a short-acting corticosteroid does not
      increase blood lipid fractions in healthy alpacas, probably because of a
      competent endogenous insulin response. Corticosteroids may induce differing
      responses in camelids with depleted glycogen stores or an ineffective insulin
      response. Administration of insulin can effectively negate the hyperglycemic
      effects of hydrocortisone and augment lipoprotein clearance. Hence, insulin
      administration may be therapeutic for alpacas with hyperglycemia, hyperlipemia,
      or hyperketonemia.

PMID- 12224860
TI  - Effects of various diets on gastric tone in the proximal portion of the stomach
      of horses.
AB  - OBJECTIVE: To assess gastric tone in the proximal portion of the stomach in
      horses during and after ingestion of 4 diets (2 diets of grain and 2 diets of
      hay). ANIMALS: 6 adult horses. PROCEDURE: A polyester bag with a volume of
      approximately 1,600 ml was inserted through a gastric cannula into the proximal
      portion of the stomach of each horse. Internal pressure of the bag was maintained
      at 2 mm Hg by use of an electronic barostat, and changes in bag volume were
      recorded before, during, and after horses consumed diets of grain or hay. Each
      horse was fed 0.5 and 1.0 g of grain/kg and 0.5 and 1.0 g of hay/kg. Changes in
      bag volume measured by use of the barostat were indirectly related to changes in
      tone of the gastric wall. RESULTS: Food intake caused a distinctly significant
      biphasic increase in volume. The first phase was during active ingestion, which
      was followed shortly by a second, more prolonged postprandial phase. The
      ingestion-related phase of the response to intake of a diet of 1 g of hay/kg was
      significantly greater than that for the other diets. CONCLUSIONS AND CLINICAL
      RELEVANCE: ingestion of a solid meal induces a biphasic relaxation response in
      the proximal portion of the stomach of horses. Magnitude of the ingestion-related
      phase may be determined by size of the meal.

PMID- 12224861
TI  - Evaluation of tartrate-resistant acid phosphatase and cathepsin K in ruptured
      cranial cruciate ligaments in dogs.
AB  - OBJECTIVE: To determine localization of tartrate-resistant acid phosphatase
      (TRAP) and cathepsin K in ruptured and healthy cranial cruciate ligaments (CCL)
      in dogs. ANIMALS: 30 dogs with ruptured CCL, 8 aged dogs without ruptured CCL,
      and 9 young dogs without ruptured CCL. PROCEDURE: The CCL was examined
      histologically and cells containing TRAP and cathepsin K were identified
      histochemically and immunohistochemically, respectively. RESULTS: Cathepsin K and
      TRAP were detected within the same cells, principally within the epiligamentous
      region and to a lesser extent in the core region of ruptured CCL. Numbers of
      cells containing TRAP and cathepsin K were significantly greater in ruptured CCL,
      compared with CCL from young or aged dogs, and numbers of such cells were greater
      in CCL from aged dogs, compared with those of young dogs. In aged dogs, small
      numbers of cells containing TRAP and cathepsin K were seen in intact CCL
      associated with ligament fascicles in which there was chondroid transformation of
      ligament fibroblasts and disruption of the extracellular matrix. CONCLUSIONS AND
      CLINICAL RELEVANCE: Ruptured CCL contain greater numbers of cells with the
      proteinases TRAP and cathepsin K than CCL from healthy, young, or aged dogs.
      Results suggest that cell-signaling pathways that regulate expression of these
      proteinases may form part of the mechanism that leads to upregulation of
      collagenolytic ligament remodeling and progressive structural failure of the CCL
      over time.

PMID- 12224862
TI  - Immunohistochemical analysis of matrix metalloproteinase-1, -3, and -13 in
      naturally occurring cartilaginous tumors of dogs.
AB  - OBJECTIVE: To determine immunoreactivity of matrix metalloproteinase (MMP)-1, -3,
      and -13 in cartilaginous tumors of dogs, correlate expression of MMP with
      histologic grade of tumors and clinical outcome of dogs, and compare MMP
      immunoreactivity between chondrosarcomas and chondromas. SAMPLE POPULATION:
      Formalin-fixed, paraffin-embedded tissues obtained from samples of naturally
      occurring chondrosarcomas (n = 31) and chondromas (8) of dogs that were submitted
      to our veterinary medical diagnostic laboratory. PROCEDURE: Histologic sections
      from each sample were stained with H&E and monoclonal antibody to MMP-1, -3, and 
      13 by use of an avidin-peroxidase immunohistochemical technique. For each
      section, histologic grade (I, II, or III) and immunohistochemical expression (0,
      1, 2, or 3) were evaluated. Clinical outcome was obtained from medical records or
      interviews with referring veterinarians and scored as a good outcome, moderate
      outcome, or poor outcome. Correlations among variables and differences between
      chondrosarcomas and chondromas were analyzed. RESULTS: Samples from
      chondrosarcomas had significantly higher immunoreactivity of MMP-1 and -13,
      compared with immunoreactivity in samples from chondromas. In chondrosarcomas, a
      significant positive correlation (r, 0.386) was found between MMP-1 and -13
      immunoreactivities, and a significant negative correlation (r, -0.390) was
      detected between MMP-3 and -13 immunoreactivities. CONCLUSIONS AND CLINICAL
      RELEVANCE: A significant increase in expression of collagenases (MMP-1 and -13)
      in chondrosarcomas, compared with expression in chondromas, suggests that
      collagenases may play an important role in tumor progression, and possibly
      metastasis, in chondrosarcomas of dogs.

PMID- 12224863
TI  - Effect of intraluminal distention on microvascular perfusion in the equine small
      colon.
AB  - OBJECTIVE: To determine the effect of experimental intraluminal distention on
      microvascular perfusion of the small colon in horses. ANIMALS: 6 mixed-breed
      healthy horses (mean age [+/- SDI, 9.1 +/- 2 years). PROCEDURE: Under general
      anesthesia, the small colon was exposed by celiotomy and 3 segments were
      demarcated. In 1 of these segments, intraluminal obstruction was created by
      placement of a latex balloon inflated to a pressure of 40 mm Hg (obstructed
      segment). The other segments were the sham-operated segment and the control
      segment. Microvascular perfusion was evaluated in the mucosal, submucosal,
      muscular, and serosal layers by injection of 15 microm-diameter colored
      microspheres into branches of the caudal mesenteric artery. Recovery of
      microspheres was performed by tissue digestion, washing, and centrifugation.
      Distribution of microspheres in the intestinal layers was evaluated by direct
      observation of stained frozen sections by light microscopy. RESULTS: A
      significant reduction was observed in total microvascular perfusion of obstructed
      segments, which was 26.4% of that of control segments. This reduction was not
      evident in the mucosal layer. CONCLUSIONS AND CLINICAL RELEVANCE: Intraluminal
      distention of the equine small colon wall can promote ischemia by a reduction in
      microvascular perfusion in the intestinal wall. Intestinal layers do not seem to
      be affected to the same extent, because the absolute value for mucosal perfusion
      did not decrease in the obstructed segment.

PMID- 12224864
TI  - Polymerase chain reaction-restriction fragment length polymorphism analysis of
      the SzP gene of Streptococcus zooepidemicus isolated from the respiratory tract
      of horses.
AB  - OBJECTIVE: To develop polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) analysis for molecular typing of strains of Streptococcus
      zooepidemicus and to use the new typing method to analyze a collection of
      isolates from the respiratory tract of Thoroughbreds. SAMPLE POPULATION: 10
      strains of S zooepidemicus, 65 isolates from the respiratory tract of 9 yearlings
      following long distance transportation, and 89 isolates from tracheal aspirates
      of 20 foals with pneumonia. PROCEDURE: Phenotypic variations in the SzP protein
      were detected by western immunoblot analysis. Using PCR-RFLP analysis, genotypes
      were obtained with primer sets from the SzP gene, followed by restriction
      endonuclease digestion of the amplicons. RESULTS: Unique genotypic patterns were
      obtained with a primer set designed from both ends of the structural gene and the
      restriction endonuclease DdeI. Forty-five isolates from the lymphoid tissue
      within the pharyngeal recess (ie, pharyngeal tonsil) of yearlings included 10 SzP
      genotypes and SzP phenotypes. Isolates from the trachea of each yearling were of
      a single genotype that was also present among isolates from the pharyngeal tonsil
      of the same horses. Isolates from tracheal aspirates of foals belonged to 14
      genotypes. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of the SzP gene by use of
      PCR-RFLP was effective for molecular typing of strains of S zooepidemicus in the
      study of respiratory tract disease in horses. Results of PCR-RFLP analysis
      indicate that a single strain of S zooepidemicus can migrate from the pharyngeal
      tonsil to the trachea at a high rate in horses undergoing long distance
      transportation.

PMID- 12224865
TI  - Effect of inhaled endotoxin on cardiopulmonary function and E-selectin expression
      in pigs.
AB  - OBJECTIVE: To evaluate the effect of controlled exposure to inhaled
      lipopolysaccharides (LPS) on the pulmonary inflammatory response of anesthetized
      pigs. ANIMALS: Forty-seven 8- to 12-week-old domestic pigs. PROCEDURE: Pigs were
      anesthetized with pentobarbital, instrumented for measurement of cardiopulmonary
      function, and randomly assigned to receive saline (0.9% NaCI) solution or 0.25,
      0.5, or 1.0 microg of LPS/kg/h for 2 or 6 hours via nebulization through the
      endotracheal tube. Cardiopulmonary variables were measured, ex vivo neutrophil
      superoxide production determined, and postmortem assessment for pulmonary
      neutrophil influx and modulation of adhesion molecule (E-selectin) expression was
      done. RESULTS: Mild changes in cardiopulmonary function were observed in response
      to inhaled LPS in the 2-and 6-hour groups. In pigs inhaling LPS (0.5 or 1.0
      microg/kg/h) for 6 hours, there was significant pulmonary neutrophil influx
      observed postmortem. An increase in expression of E-selectin on pulmonary
      endothelial cells after 6 hours of LPS inhalation (0.5 microg/kg/h) was also
      observed. In contrast, there was no significant influx of neutrophils or
      expression of E-selectin in lungs from pigs inhaling LPS for 2 hours. CONCLUSIONS
      AND CLINICAL RELEVANCE: inhalation of LPS resulted in localized pulmonary
      inflammation characterized by neutrophil influx and increased expression of the
      endothelial cell adhesion molecule, E-selectin. It may be possible to relate our
      experimental findings to the clinical consequences of airborne LPS exposure in
      swine confinement facilities.

PMID- 12224866
TI  - Transdermal absorption of a liposome-encapsulated formulation of lidocaine
      following topical administration in cats.
AB  - OBJECTIVE: To determine plasma disposition after dermal application of a liposome
      encapsulated formulation of lidocaine in cats. ANIMALS: 6 healthy adult cats with
      a mean (+/- SD) body weight of 4.1 +/- 0.44 kg. PROCEDURE: CBC determination and
      biochemical analysis of blood samples were performed for all cats. Cats were
      anesthetized by use of isoflurane, and catheters were placed IV in a central
      vein. The next day, blood samples were obtained from the catheters before and 1,
      2, 3, 4, 6, 8, 10, 12, and 24 hours after applying a 4% liposome-encapsulated
      lidocaine cream (15 mg/kg) to a clipped area over the cephalic vein. Plasma
      concentrations of lidocaine were analyzed with a high-performance liquid
      chromatography assay. Results-Two cats had minimal transdermal absorption of
      lidocaine, with lidocaine concentrations below the sensitivity of the assay at
      all but 1 or 2 time points. In the other 4 cats, the median maximum plasma
      concentration was 149.5 ng/ml, the median time to maximum plasma concentration
      was 2 hours, and the median area under the concentration versus time curve from
      zero to infinity was 1014.5 ng.h/ml. CONCLUSIONS AND CLINICAL RELEVANCE: Maximum
      plasma concentrations of lidocaine remained substantially below toxic plasma
      concentrations for cats. On the basis of these data, topical administration of a
      liposome-encapsulated lidocaine formulation at a dose of 15 mg/kg appears to be
      safe for use in healthy adult cats.

PMID- 12224867
TI  - Laparoscopic-assisted enterostomy tube placement and full-thickness biopsy of the
      jejunum with serosal patching in dogs.
AB  - OBJECTIVE: To develop laparoscopic-assisted techniques for enterostomy feeding
      tube placement and full-thickness biopsy of the jejunum in dogs. ANIMALS: 15
      healthy dogs. PROCEDURE Dogs were anesthetized, and positive pressure ventilation
      was provided. A trocar cannula for the laparoscope was inserted on the ventral
      midline caudal to the umbilicus. For enterostomy tube placement, a second trocar
      cannula was placed lateral to the right rectus abdominis muscle, and a Babcock
      forceps was used to grasp the duodenum and elevate it to the incision made for
      the cannula. The duodenum was sutured to the abdominal wall, and a feeding tube
      was inserted. For jejunal biopsy, a third trocar cannula was placed lateral to
      the left rectus abdominis muscle. A portion of jejunum was elevated to the
      incision for the second or third cannula, and a full-thickness biopsy specimen
      was obtained. A second specimen was obtained from another portion of jejunum, and
      retention sutures for the 2 biopsy sites were tied so that serosal surfaces of
      the biopsy sites were apposed to each other. Dogs were euthanatized 30 days after
      surgery. RESULTS: The enterostomy tube was properly positioned and functional in
      all 8 dogs that underwent laparoscopic-assisted enterostomy tube placement, and
      sufficient samples for histologic examination were obtained from all 7 dogs that
      underwent laparoscopic-assisted jejunal biopsy. None of the dogs had any
      identifiable problems after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggest that in dogs, laparoscopic-assisted procedures for enterostomy tube
      placement and jejunal biopsy are an acceptable alternative to procedures
      performed during a laparotomy.

PMID- 12224868
TI  - Effects of theophylline on tracheal mucociliary clearance rates in healthy cats.
AB  - OBJECTIVE: To determine tracheal mucociliary clearance rate (TMCCR) by use of a
      standard protocol in healthy anesthetized cats and to determine the effect of
      theophylline on TMCCR in healthy anesthetized cats. ANIMALS: 6 healthy cats.
      PROCEDURE: Cats were anesthetized with propofol, and a droplet of the
      radiopharmaceutical technetium Tc 99m macroaggregated albumin was placed
      endoscopically at the carina. Dynamic acquisition scintigraphic imaging was
      performed, using the larynx as the end point. The TMCCR was determined by
      measuring the distance the droplet traveled by frame rate. Each cat was imaged 6
      times as follows: 3 times following placebo administration and 3 times following
      the administration of sustained release theophylline (25 mg/kg, PO). Serum
      theophylline concentrations were assessed during imaging to ensure therapeutic
      concentrations. RESULTS: The TMCCR in healthy adult cats anesthetized with
      propofol was 22.2 +/- 2.8 mm/min. Tracheal mucociliary clearance rate in cats
      receiving theophylline was 21.8 +/- 3.5 mm/min. Theophylline administration did
      not significantly alterTMCCR. CONCLUSIONS AND CLINICAL RELEVANCE: Theophylline
      has been shown to increase TMCCR in humans and dogs. In our study, we determined
      TMCCR in healthy anesthetized cats and found that it was not accelerated by the
      administration of theophylline.

PMID- 12224869
TI  - Influence of age and body size on intestinal permeability and absorption in
      healthy dogs.
AB  - OBJECTIVE: To evaluate effects of age and body size of dogs on intestinal
      permeability (unmediated diffusion) as measured by the ratio of urinary lactulose
      to L-rhamnose (L:R) and absorption (carrier-mediated transport) as measured by
      the ratio of urinary D-xylose to 3-O-methyl-D-glucose (X:MG) and to determine
      whether these variables correlated with fecal quality. ANIMALS: 6 Miniature
      Poodles, 6 Standard Schnauzers, 6 Giant Schnauzers, and 6 Great Danes. PROCEDURE:
      A solution that contained lactulose and rhamnose or xylose and 3-O-methyl-D
      glucose was administered orally to dogs that were 12, 22, 36, and 60 weeks old.
      Urine was collected 6 hours later, and urinary L:R and X:MG were calculated.
      Fecal moisture and scoring were recorded during the same periods. RESULTS: Age
      and breed did not affect intestinal absorption, and we did not detect a
      relationship between X:MG and fecal variables. In contrast, we detected
      significant effects of age and body size on intestinal permeability. Puppies (12
      weeks old) and large dogs had higher intestinal permeability than adult (60 weeks
      old) and small dogs. The increased intestinal permeability in large dogs was
      associated with lower fecal quality as indicated by the significant positive
      correlations between L:R and fecal moisture (r, 0.61) and L:R and fecal scores
      (r, 0.86) in adult dogs. CONCLUSIONS AND CLINICAL RELEVANCE: These results
      indicate that age and body size should be considered when assessing intestinal
      permeability by use of the L:R urinary excretion test in dogs. High intestinal
      permeability could be a possible cause of poor fecal quality in large dogs.

PMID- 12224870
TI  - Evaluation of the usefulness of sensitization to aeroallergens as a model for
      canine atopic dermatitis in genetically predisposed Beagles.
AB  - OBJECTIVE: To evaluate a model for atopic dermatitis (AD) and to measure the
      effect of sensitization in Beagles genetically predisposed to produce high serum
      concentrations of allergen specific IgE. ANIMALS: 22 laboratory Beagles.
      PROCEDURE: Seventeen dogs were sensitized from birth to 3 allergens (recombinant
      birch pollen, Dermatophagoides pteronyssinus, and D farinae). Five nonsensitized
      dogs from the same litters served as controls. Clinical scoring, regular
      intradermal testing, measurement of serum concentrations of allergen-specific
      IgE, and collection of biopsy specimens of skin at 23, 32, and 43 weeks of age
      were performed. Serial tissue sections were stained for identification of IgE+
      cells, mast cells and their subtypes, T-cells, Langerhans cells, and major
      histocompatibility complex class-II+ cells. At the age of 15 months, dogs were
      continuously exposed to 2 microg of mite allergen/g of dust. RESULTS: Sensitized
      dogs had positive intradermal test reactions and significantly higher serum
      concentrations of allergen specific IgE, compared with nonsensitized dogs. In
      sensitized and nonsensitized dogs, a significantly higher number of mast cells
      was found at predilection sites, compared with the control biopsy site. The
      number of mast cells at predilection sites increased with age. Sensitization
      significantly increased the number of epidermal Langerhans cells by 23 weeks of
      age. The number of epidermal Langerhans cells significantly increased in
      nonsensitized dogs by 32 weeks of age. Clinical scoring only revealed mild
      transient erythema in some dogs. CONCLUSIONS: increases in concentrations of
      serum allergen-specific IgE and exposure to allergens is not sufficient to induce
      clinical signs of AD in genetically predisposed dogs.

PMID- 12224871
TI  - General competencies and accreditation in graduate medical education.
AB  - Many have recommended changing the professional development of physicians.
      Concluding that further educational process specification was inadequate, the
      Accreditation Council for Graduate Medical Education (ACGME) decided to specify
      six general competencies of graduate medical education (GME): patient care;
      medical knowledge; practice-based learning and improvement; professionalism;
      interpersonal skills and communication; and systems-based practice. Coupling them
      with a developmental view of professional knowledge and skill acquisition, the
      ACGME invited further specification and development of desired learning from the
      extended medical specialty community, including the specialty boards. This
      collaborative process offers a model of the role accrediting agencies can play in
      fostering workforce developmental change.

PMID- 12224872
TI  - Time-capsule thinking: the health care workforce, past and future.
AB  - The size and shape of the U.S. health care workforce are in constant evolution.
      Using the metaphorical device of a time capsule, this essay examines the past and
      future of the workforce. It traces the growth, specialization, and
      diversification of health care workers during the twentieth century, emphasizing
      the particular expansion of the nonmedical aspects of the workforce. Looking
      ahead, the paper examines technology, informatics, nursing, provider
      distribution, and the global migration of health care workers as pivotal issues
      for the future of the workforce.

PMID- 12224873
TI  - Strengthening hospital nursing.
AB  - Hospitals, nurses, the media, Congress, and the private sector are increasingly
      concerned about shortages of registered nurses (RNs) and the impact on safety and
      quality of patient care. Findings from a growing number of studies provide
      evidence of a relationship between hospital nurse staffing and adverse outcomes
      experienced by medical and surgical patients. These findings have policy
      implications for strengthening the nursing profession, monitoring the quality of
      hospital care associated with nursing, and improving the relationship between
      hospitals and the nursing profession.

PMID- 12224874
TI  - Fighting hand to hand over physician workforce policy.
AB  - A vexing problem in health policy is getting the right number of physicians in
      the right specialties in the right locations at the right time. I examine market
      and public planning approaches to getting the number "right." After discussing
      the basic premises of the invisible hand of the market and the heavy hand of
      government regulation, I apply these concepts to a review of the past century of
      U.S. physician supply and workforce policy. I conclude by examining recent health
      system trends that make clear the need for a firm regulatory grasp on physician
      workforce policy.

PMID- 12224875
TI  - Can nurse practitioners and physicians beat parochialism into plowshares?
AB  - Nurse practitioners have evolved into a large and flexible workforce. Far too
      often, nurse practitioner and physician professional organizations do not work
      together but rather expend considerable effort jousting in policy arenas. Turf
      battles interfere with joint advocacy for needed health system change and delay
      development of interdisciplinary teams that could help patients. A combined,
      consistent effort is urgently needed for studying, training, and deploying a
      collaborative, integrated workforce aimed at improving the health care system of
      tomorrow. The country can ill afford doctors and nurses who ignore one another's
      capabilities and fail to maximize each other's contributions cost-effectively.

PMID- 12224876
TI  - Job-based health benefits in 2002: some important trends.
AB  - Based on a national survey of 2,014 randomly selected public and private firms
      with three or more workers, this paper reports changes in employer-based health
      insurance from spring 2001 to spring 2002. The cost of health insurance rose 12.7
      percent, the highest rate of growth since 1990. Employee contributions for health
      insurance rose in 2002, from $30 to $38 for single coverage and from $150 to $174
      for family coverage. Deductibles and copayments rose also, and employers adopted
      formularies and three-tier cost-sharing formulas to control prescription drug
      expenses. PPO and HMO enrollment rose, while the percentage of small employers
      offering health benefits fell. Because increasing claims expenses rather than the
      underwriting cycle are the major driver of rising premiums, double-digit growth
      appears likely to continue.

PMID- 12224877
TI  - Physician credentialing in a consumer-centric world.
AB  - As managed care responds to the rising tide of consumerism in medicine, it is
      necessary to reexamine the functions that health plans have performed. Chief
      among the activities that demand resources but return minimal value is the
      process of physician credentialing. As consumers are asked to assume more control
      in their health care decisions and to pay more for their care, the credentialing
      process must be changed if it is to add value for consumers. This paper discusses
      the role of credentialing and how it might be reconfigured to become more
      meaningful to consumers.

PMID- 12224878
TI  - Nursing shortage redux: turning the corner on an enduring problem.
AB  - Projections of a substantial nursing workforce imbalance in the coming decade
      have galvanized policymakers, providers, private foundations, nurses, and others
      to proffer aggressive and sustainable strategies to ameliorate the looming
      shortage. The solutions are largely ones that seek to increase supply. Analysis
      of the 1992-2000 National Sample Surveys of Registered Nurses shows that
      increasing losses from the active workforce, stagnant wages, and low levels of
      job satisfaction pose major impediments to bolstering supply. Strategies focused
      on working conditions and retention should occupy a central position in any
      nursing workforce revitalization plan.

PMID- 12224879
TI  - Trends in the physician workforce, 1980-2000.
AB  - Over the past twenty-five years the nation has struggled with a series of
      physician workforce issues: determining the appropriate number of physicians
      needed and the appropriate number to produce; the role of international medical
      school graduates; the mix of primary care and non-primary care physicians;
      efforts to increase the number of underrepresented minorities in medicine and the
      supply of physicians in rural areas; and the impact of the growing number of
      female physicians. This paper documents physician workforce trends over the past
      twenty years, especially as they relate to these issues.

PMID- 12224880
TI  - Trends in the supply of physician assistants and nurse practitioners in the
      United States.
AB  - In 2001 an estimated 103,612 nurse practitioners (NPs) and physician assistants
      (PAs) were in clinical employment in the United States. The roles of PAs and NPs
      in providing comparable physician services are similar; they differ in that NPs
      are predominantly in primary care, while PAs are divided between primary and
      specialty care. PA and NP education processes also differ in the student pool and
      trends in the output. The combined number of graduates totaled 11,585 in 2001.
      However, the annual number of NP graduates is declining, while the number of PA
      graduates is increasing. These observations have implications for the future in
      the types of patients they see and the degree of health care services they
      provide.

PMID- 12224881
TI  - Challenges to the pharmacist profession from escalating pharmaceutical demand.
AB  - Unexpected growth in medication use has escalated demand for pharmacists that has
      outpaced supply. Responses to the pharmacist shortage include larger workloads
      and greater use of pharmacist extenders and technology. As the profession has
      moved from a product orientation (dispensing medications) to a patient focus,
      clinical training requirements have expanded. However, structural and process
      barriers, particularly in community and retail pharmacies, must be addressed to
      improve the medication-use process. These issues merit greater attention from
      health care leaders and policymakers.

PMID- 12224882
TI  - Nursing workforce retention: challenging a bullying culture.
AB  - Discussions surrounding nursing shortages typically focus on recruitment, but
      retention is also a problem. Emerging research suggests that intimidation in the
      nursing workforce is a problem that planners need to deal with as part of an
      overall strategy aimed at maintaining a balance between supply and demand. This
      paper explores issues surrounding intimidation in the nursing workforce and looks
      at how one major teaching hospital in Australia attempted to address the problem.

PMID- 12224883
TI  - Obstacles to employers' pursuit of health care quality.
AB  - Large employers' roles in improving health care quality are shifting away from
      value-based purchasing toward direct efforts to improve health care delivery
      within local markets. Although most large employers adopted the tools required
      for value-based purchasing, inadequate information on quality has frustrated
      employers and limited their ability to make choices based on quality. More recent
      quality initiatives aimed at directly improving local health delivery systems may
      be limited to specific markets where the largest employers can exert substantial
      influence.

PMID- 12224884
TI  - Quality improvement by providers: market developments hinder progress.
AB  - Providers report maintaining, but not greatly enhancing, their quality
      improvement (QI) programs between 1999 and 2001. In addition, recent market
      developments are intensifying barriers to providers' QI efforts. A notable
      exception is the tremendous attention to medical errors, which is stimulating
      patient-safety activities in hospitals. It is too early to tell if the momentum
      from these activities can be sustained and provide a spark for revolutionary
      changes in QI more broadly.

PMID- 12224885
TI  - Back to the drawing board: new directions in health plans' care management
      strategies.
AB  - The backlash against managed care has pressured health plans to reexamine their
      approaches to controlling utilization and managing their members' health care
      needs, but how much has really changed? Interviews with health plans and others
      in twelve nationally representative markets suggest that the changes are
      significant. New and refined disease management programs are improving the care
      experience of participants with certain prevalent chronic illnesses, while
      utilization management changes are reducing the administrative burden for
      providers. Still, disease management programs will need to greatly expand in
      scope and scale if plans are to succeed in addressing the complex health care
      needs of aging populations and those with chronic diseases.

PMID- 12224886
TI  - Dolores.

PMID- 12224887
TI  - The benefits divide: health care purchasing in retail versus other sectors.
AB  - This paper is the first to compare health care purchasing in the retail versus
      other sectors of the Fortune 500. Employing millions of low-wage workers, the
      retail sector is the largest employer of uninsured workers in the economy. We
      found that retail companies are using the same competitive bidding process that
      other companies use to obtain a given level of coverage for the lowest possible
      cost. However, they are more price oriented than other Fortune 500 companies are.
      The most striking disparity lies in the nearly fivefold difference in offer rates
      for health care coverage. This shows that the economy's bifurcation in health
      benefits extends even to the nation's largest companies.

PMID- 12224888
TI  - Will volume-based referral strategies reduce costs or just save lives?
AB  - Although recent policy initiatives aimed at concentrating selected surgical
      procedures in high-volume hospitals may reduce mortality, their economic
      implications have not been considered fully. From the hospital perspective, the
      primary effect of these policies will be to redistribute surgical profits to
      bigger centers. From the payer perspective, prices paid for procedures will
      likely increase in some geographic areas. From the societal perspective, how
      these policies will affect the true cost of providing surgical care is uncertain,
      but use of discretionary procedures will likely increase. For these reasons, the
      primary argument for volume-based referral strategies should be improving
      quality, not reducing costs.

PMID- 12224889
TI  - Employing persons with serious mental illness.
AB  - Data from various national surveys find that approximately half the population
      with mental disorders is gainfully employed across the entire range of
      occupations; such persons have an employment rate of about two-thirds that of the
      general population. More than a third of persons with serious mental illness also
      work, and many hold high-status positions. Among those with schizophrenia, a
      diagnosis associated with high impairment, only slightly more than a fifth are at
      work, and 12 percent are working full time. Approximately two-thirds are enrolled
      in federal disability insurance programs. Our analyses indicate considerable
      diversity of jobs among persons with various mental disorders. Most persons with
      mental illness want to work, and some with even the most serious mental disorders
      hold jobs requiring high levels of functioning. Educational attainment is the
      strongest predictor of employment in high-ranking occupations among both the
      general population and persons with mental disorders.

PMID- 12224890
TI  - Access to postacute nursing home care before and after the BBA. Balanced Budget
      Act.
AB  - Anecdotal reports in the wake of the Balanced Budget Act (BBA) of 1997 raised
      concerns about restricted access to postacute nursing facility care for Medicare
      beneficiaries requiring costly, medically complex services. Using all Medicare
      Part A hospital and nursing facility claims for providers in the state of Ohio
      and a refined method of identifying hospitalized beneficiaries who were the most
      at risk, we observed only a small decrease in the proportion of the costliest
      patients discharged to nursing facilities in 1999 compared with pre-BBA years.
      Average hospital length-of-stay increased only slightly in 1999, and there were
      no changes in rehospitalization rates for the costliest patient types. However,
      reduced rates of admission were concentrated in specific types of nursing
      facilities, suggesting a need to closely monitor the effects of ongoing post-BBA
      policy updates.

PMID- 12224891
TI  - Health research philanthropy in a time of plenty: a strategic agenda.
AB  - Generous public investment in the National Institutes of Health (NIH) provides
      research foundations with a unique opportunity to more closely connect
      investments in basic research to a payoff in improved health. Foundations can
      support efforts to integrate what is known from the biological, behavioral, and
      social sciences to solve the nation's most pressing health problems. In doing so,
      they will help to build the scientific capacity to conduct high-quality
      integrative research in anticipation of a more robust public investment in
      translating what is known about health into what is done to improve and maintain
      it.

PMID- 12224892
TI  - Monitoring local safety-net providers: do they have adequate capacity?
AB  - The safety-net providers that serve the nation's thirty-nine million uninsured
      residents are vulnerable organizations even in good economic times, yet efforts
      to monitor their capacity have been limited at best. This study of the safety-net
      in five cities found that capacity was strained for specialty services and that
      access to pharmaceuticals was difficult, while primary care capacity was more
      often adequate to serve those who presented themselves for care. Also, free
      clinics grew during the 1990s, while many other safety-net providers focused on
      improving their efficiency and collecting more fees from patients.

PMID- 12224893
TI  - Dreaming the American dream: once more around on physician workforce policy.

PMID- 12224894
TI  - Promising practices: how leading safety-net plans are managing the care of
      Medicaid clients.
AB  - Health plans formed by safety-net providers serve large numbers of Medicaid
      beneficiaries. Through a series of case studies, we examined the care management
      tools used by leading safety-net plans. These plans do not rely on the coercive,
      command-style tools of managed care. They rely instead on tools that emphasize
      partnership with providers: sharing data about practice patterns, using provider
      profiles and financial bonuses to encourage particular practice patterns, and
      developing disease management programs that encourage patient compliance with
      treatment decisions that the plans make little effort to shape. The evidence
      suggests that these are promising practices but that even these leaders still
      have a long way to go.

PMID- 12224895
TI  - National health insurance.

PMID- 12224896
TI  - Putting money into effective treatments.

PMID- 12224897
TI  - Health investment costs and benefits.

PMID- 12224898
TI  - Economics and priority setting.

PMID- 12224899
TI  - Quality chasm factors.

PMID- 12224900
TI  - Hope for enhanced efficiency.

PMID- 12224901
TI  - The will and capacity to improve quality.

PMID- 12224902
TI  - HMO performance: the debate goes on.

PMID- 12224903
TI  - Protecting ambulatory surgery patients.

PMID- 12224904
TI  - Report card bias.

PMID- 12224905
TI  - Pharmacogenetic challenges.

PMID- 12224906
TI  - Interstate highway system for medical records.

PMID- 12224907
TI  - Effects of current and future information technologies on the health care
      workforce.
AB  - Information technologies have the potential to affect the types and distribution
      of jobs in the health care workforce. Against a background of an explosively
      growing body of knowledge in the health sciences, current models of clinical
      decision making by autonomous practitioners, relying upon their memory and
      personal experience, will be inadequate for effective twenty-first-century health
      care delivery. The growth of consumerism and the proliferation of Internet
      accessible sources of health-related information will modify the traditional
      roles of provider and patient and will provide opportunities for new kinds of
      employment in health-related professions.

PMID- 12224908
TI  - Arching the flood: how to bridge the gap between nursing schools and hospitals.
AB  - A gap persists between what nurses can do and what they are employed to do,
      between the education nurses obtain and the work design of hospitals. Despite
      agonizing over standardization, current nursing education reflects the
      pluralistic nursing workforce, and nurses hold accountability for it. But nurses
      have not been proportionately or effectively involved in restructuring the
      hospital workplace. The result is that nurses are both overworked and underused.
      Fortunately, this gap may be bridged with a number of short- and long-term policy
      solutions.

PMID- 12224909
TI  - Minimum nurse-to-patient ratios in acute care hospitals in California.
AB  - Many registered nurses believe that nurse staffing in acute care hospitals is
      inadequate. In 1999 California became the first state to mandate minimum nurse-to
      patient ratios in hospitals. State officials announced draft ratios in January
      2002 and expect to implement the legislation by July 2003. We estimate that the
      direct costs of compliance will be small. However, mandatory ratios could
      generate opportunity costs that are not easily measured and that may outweigh
      their benefits. Policymakers elsewhere should consider other strategies to
      address nurses' concerns, because other approaches may be less costly and produce
      greater benefits to nurses and patients.

PMID- 12224910
TI  - The growing challenge of providing oral health care services to all Americans.
AB  - By many measures, the practice of dentistry has improved for the dentist over the
      past decade. Hours of work are down, and compensation is increasing. However,
      there is a growing disconnect between the dominant pattern of practice of the
      profession and the oral health needs of the nation. To address these needs, the
      profession will need to take some radical steps toward redefinition, or the
      responsibility for many for these needs and special populations may shift to
      other providers and other institutions.

PMID- 12224911
TI  - Who cares for older adults? Workforce implications of an aging society.
AB  - There is a critical shortage of geriatrics-prepared health care professionals. In
      2002 more than thirty-five million people were age sixty-five and older, and 23
      percent of them reported poor or fair health. Older adults use 23 percent of
      ambulatory care visits and 48 percent of hospital days, and they represent 83
      percent of nursing facility residents. Yet 58 percent of baccalaureate nursing
      programs have no full-time faculty certified in geriatric nursing. Only three of
      the nation's 145 medical schools have geriatrics departments, and less than 10
      percent of these require a geriatrics course. We argue that every health care
      worker must have some education in geriatrics and access to geriatrics care
      experts.

PMID- 12224915
TI  - (15)N-(1)H bond length determination in natural abundance by inverse detection in
      fast-MAS solid-state NMR spectroscopy.
AB  - A solid-state 15N-1H correlation NMR experiment is presented, which provides a
      substantial gain in signal sensitivity by 1H inverse detection under fast MAS
      conditions and allows for the precise determination of NH bond lengths via
      heteronuclear 1H-15N dipole-dipole couplings on samples naturally abundant in
      15N. Pulsed-field gradients or, alternatively, radio frequency pulses ensure
      suppression of unwanted 1H signals. In this way, natural-abundance 15N-1H
      correlation NMR spectroscopy becomes feasible in the solid state with experiment
      times of a few hours. The dipole-dipole coupling constants are extracted from
      spinning sideband patterns generated by recently developed recoupling strategies.
      The information on 15N/1H chemical shifts and quantitative 15N-1H couplings can
      readily be combined in a single two-dimensional spectrum using a split-t1
      approach.

PMID- 12224912
TI  - The case for diversity in the health care workforce.
AB  - Increasing the racial and ethnic diversity of the health care workforce is
      essential for the adequate provision of culturally competent care to our nation's
      burgeoning minority communities. A diverse health care workforce will help to
      expand health care access for the underserved, foster research in neglected areas
      of societal need, and enrich the pool of managers and policymakers to meet the
      needs of a diverse populace. The long-term solution to achieving adequate
      diversity in the health professions depends upon fundamental reforms of our
      country's precollege education system. Until these reforms occur, affirmative
      action tools in health professions schools are critical to achieving a diverse
      health care workforce.

PMID- 12224917
TI  - Supramolecular structures of polyoxomolybdate-based giant molecules in aqueous
      solution.
AB  - A combination of static and dynamic laser light-scattering techniques was
      employed to study the supramolecular structures of polyoxomolybdate-based giant
      molecules in aqueous solution. Convincing evidences indicate that the spherical
      aggregates have unique vesicle-like structures. A model is built up based on
      solid experimental results. It is the first time that a clear explanation is
      presented for the long-time enigma in inorganic chemistry: the nature of the
      polyoxomolybdate aggregates in "molybdenum blue solution".

PMID- 12224916
TI  - The indole side chain of tryptophan as a versatile pi-donor.
AB  - Single-armed, 15- and 18-membered lariat ether receptor systems having
      indolylethyl side arms bind Na+ and K+ in the ring. The indole residue serves as
      a pi-donor to the ring-bound cation. Whether the five- or six-membered ring
      interacts most directly with Na+ or K+ depends on whether the sidearm is attached
      to indole's 3- or 5-position. This suggests that structural as well as electronic
      factors are important in pi-complexation of alkali metal cations.

PMID- 12224918
TI  - Single-crystal-to-single-crystal transformation of diolefin derivatives in
      nanocrystals.
AB  - Topochemical [2 + 2] cycloaddition polymerization of methyl p-phenylenediacrylate
      and 2,5-distyrylpyridine in nanocrystals, prepared by the reprecipitation method,
      were investigated in comparison with those in bulk crystals. The bulk single
      crystals, larger than 1 mum in size, broke into microcrystals with variety of
      size and shape in the course of polymerization. Interestingly, however, these
      nanocrystals show single-crystal-to-single-crystal transformation.

PMID- 12224919
TI  - An artificial guanine that binds cytidine through the cooperative interaction of
      metal coordination and hydrogen bonding.
AB  - Cd(II) complex of L binds selectively to cytidine in DMSO with an equilibrium
      constant of 117 M-1 (where LH is 2-aminomethyl-8-hydroxyquinoline). In contrast,
      the Zn(II) complex of L does not bind appreciably to any of the four nucleobases
      under the same condition used for the Cd(II) complex.

PMID- 12224920
TI  - Synergistic effect between metal coordination and hydrogen bonding in phosphate
      and halide recognition.
AB  - The equilibrium constant for binding of dimethyl phosphate to a Co(III) complex
      in water increases from 6.2 to 210 M-1 upon addition of a single hydrogen bond
      between the bound phosphate and the metal complex. Crystal structure reveals that
      the hydrogen bond distance is 1.96 A. The synergistic effect between metal
      coordination and hydrogen bonding can also be observed for fluoride binding but
      not for bromide binding.

PMID- 12224921
TI  - Control of the optical band structure of liquid crystal infiltrated inverse opal
      by a photoinduced nematic-isotropic phase transition.
AB  - Recently, photonic band gap (PBG) crystals with lattice parameters comparable to
      the wavelength of light have attracted much attention, because they offer unique
      ways in which to control the propagation of light. PBG crystals have applications
      in laser, quantum optical devices, and so on. For many of these applications, it
      is important to have the capability of tuning the photonic band structures. The
      fabrication of such tunable PBG crystals is still a challenge. In this paper, we
      proposed that switchable PBG crystals could be realized by taking advantage of
      the phase transition in liquid crystals induced by the photoisomerization of azo
      dyes. A dynamic change in the optical stop band was demonstrated. Such
      photoswitchable PBG crystals provide a method by which light can be routed using
      light.

PMID- 12224922
TI  - Structure of a de novo designed protein model of radical enzymes.
AB  - The use of side chains as catalytic cofactors for protein mediated redox
      chemistry raises significant mechanistic issues as to how these amino acids are
      activated toward radical chemistry in a controlled manner. De novo protein design
      has been used to examine the structural basis for the creation and maintenance of
      a tryptophanyl radical in a three-helix bundle protein maquette. Here we report
      the detailed structural analysis of the protein by multidimensional NMR methods.
      An interesting feature of the structure is an apparent pi-cation interaction
      involving the sole tryptophan and a lysine side chain. Hybrid density functional
      calculations support the notion that this interaction raises the reduction
      potential of the W degrees /WH redox pair and helps explain the redox
      characteristics of the protein. This model protein system therefore provides a
      powerful model for exploring the structural basis for controlled radical
      chemistry in protein.

PMID- 12224923
TI  - First thermally responsive supramolecular polymer based on glycosylated amino
      acid.
AB  - In materials science, a dynamic property sensitive to an environmental change
      (heat, light, electric current, pH, and other chemical or physical changes) is
      indispensable for intelligent materials. Such organic materials, however, are
      very limited even in conventional polymers. This paper clearly demonstrates that,
      regardless of the low molecular weight, a glycosylated amino acid derivative
      newly screened by a combinatorial method forms a macroscopic supramolecular
      hydrogel that reversibly swells or shrinks in response to the external
      temperature. Using the unique thermal response of the present hydrogel, we
      carried out the controlled release of DNA and the perfect removal of bisphenol A
      from the polluted water. Recently, advanced supramolecular polymers, in which
      monomers are noncovalently connected, are expected to be highly advantageous over
      traditional polymers because of their tunable and recyclable characteristics. The
      present result newly confers a dynamic feature on the supramolecular polymers,
      which is desirable for the sophisticated application in many fields.

PMID- 12224924
TI  - Oscillatory photochemical decomposition of tetrathionate ion.
AB  - When subject to illumination, tetrathionate ion decomposes in an oscillatory
      fashion with a period of about 1 h to yield products identified as colloidal
      sulfur and trithionate ion. This system represents the first experimental example
      of a stirred, batch photochemical oscillator. A simple model consisting of four
      reaction steps and four adjustable rate parameters gives good agreement with the
      observed oscillatory behavior.

PMID- 12224925
TI  - Iterative high-throughput polymorphism studies on acetaminophen and an
      experimentally derived structure for form III.
AB  - Three crystal forms of acetaminophen were prepared and characterized using a
      newly developed high-throughput crystallization platform, CrystalMax. The
      platform consists of design software, robotic sample dispensing and handling, and
      high-throughput microanalytics and is capable of running thousands of
      crystallizations in parallel using several different methods to drive
      supersaturation and subsequent crystallization. Additionally, structural models
      of the elusive third form of acetaminophen will be discussed on the basis of
      powder X-ray diffraction data. One structure suggested has a bilayer motif, held
      together by O-H...O(H) hydrogen bonds, and helps explain the difficulty
      associated with preparing this form from solution.

PMID- 12224926
TI  - New molecular perovskites: cubic C(4)N(2)H(12).NH(4)Cl(3).H(2)O and 2-H hexagonal
      C(6)N(2)H(14).NH(4)Cl(3).
AB  - The room-temperature syntheses and single-crystal structures of
      C(4)N(2)H(12).NH(4)Cl(3).H(2)O and C(6)N(2)H(14).NH(4)Cl(3) are reported. These
      novel molecular perovskites contain vertex-sharing octahedral (NH(4))Cl(6) arrays
      which replicate the octahedral packing in the cubic (SrTiO(3)) and 2-H hexagonal
      (BaNiO(3)) perovskite structures, respectively. The structures are completed by
      doubly protonated organic cations and, for the cubic phase, water molecules.
      Crystal data: C(4)N(2)H(12).NH(4)Cl(3).H(2)O, M(r) = 230.56, orthorhombic, Pbcm
      (No. 57), a = 6.5279(13) A, b = 12.935(3) A, c = 12.849(3) A, V = 1085.0(4) A(3),
      Z = 4; C(6)N(2)H(14).NH(4)Cl(3), M(r) = 238.59, trigonal, Pthremacr;c1 (No. 165),
      a = 16.1616(2) A, c = 22.3496(4) A, V = 5055.5(2) A(3), Z = 18.

PMID- 12224927
TI  - A polymerized calix[6]arene monolayer having gas permeation selectivity that
      exceeds Knudsen diffusion.
AB  - A polymerized monolayer of 5,11,17,23,29,35-hexamercaptomethyl-37,38,40,41,42
      hexakis-(1-n hexadecyloxy)calix[6]arene (1) has been synthesized on the surface
      of an ca. 15 mum-thick film derived from poly[1-(trimethylsilyl)-1-propyne]
      (PTMSP). This monolayer exhibits a permeation selectivity toward He and SF6 that
      exceeds Knudsen diffusion. Analogous membranes made from a calix[6]arene that
      contains amidoxime headgroups (i.e., 2) showed Knudsen diffusion characteristics.

PMID- 12224928
TI  - Evidence for direct attack by hydroxide in phosphodiester hydrolysis.
AB  - Phosphodiester hydrolysis has been the subject of intense study due to its
      importance in biology. Despite the numerous significant analyses of
      phosphodiester cleavage mechansim, comparatively little is known about the
      nucleophiles in these reactions. To determine whether hydroxide acts as a
      nucleophile or a general base in the hydrolysis of thymidine-5'-p-nitrophenyl
      phosphate,we determined solvent deuterium isotope effects (D2Ok), ionic strength
      effects, and 18O isotope effects on the solvent nucleophile (18knuc). The D2Ok
      for hydroxide-catalyzed phosphodiester hydrolysis is slightly inverse (0.9 +/-
      0.1), suggesting that a proton transfer does not occur in the transition state. A
      significant alpha effect is observed with hydroperoxide, demonstrating that
      oxyanions can act as nucleophiles in the reaction. Additionally, the ionic
      strength dependencies of hydroxide and hydroperoxide catalysis are
      indistinguishable, suggesting that they act by the same mechanism. Finally, the
      18knuc for the hydroxide-catalyzed reaction is 1.068 +/- 0.007, well in excess of
      the equilibrium 18O isotope effect between water and hydroxide (1.040 +/- 0.003).
      Together, the data are most consistent with direct nucleophilic attack by
      hydroxide. From the observed 18knuc and the known equilibrium component, the
      kinetic component of the isotope effect was calculated to be 1.027 +/- 0.010.
      This large kinetic component suggests that little bond order to the nucleophile
      occurs in the transition state.

PMID- 12224930
TI  - (Pi-allyl)palladium complexes bearing diphosphinidenecyclobutene ligands (DPCB):
      highly active catalysts for direct conversion of allylic alcohols.
AB  - The (pi-allyl)palladium complex bearing an sp2-hybridized phosphorus ligand (DPCB
      OMe: 1,2-bis(4-methoxyphenyl)-3,4-bis[(2,4,6-tri-tert
      butylphenyl)phosphinidene]cyclobutene) efficiently catalyzes direct conversion of
      allylic alcohols in the absence of activating agents of alcohols such as Lewis
      acids. N-Allylation of aniline proceeds at room temperature to afford
      monoallylated anilines in 90-97% yields. C-Allylation of active methylene
      compounds is also successful at 50 degrees C using a catalytic amount of pyridine
      as a base, giving monoallylation products in 85-95% yields. The catalytic
      mechanism involving hydrido- and (pi-allyl)palladium intermediates has been
      proposed on the basis of stoichiometric examinations using model compounds of
      presumed intermediates.

PMID- 12224929
TI  - Designed arginine-rich RNA-binding peptides with picomolar affinity.
AB  - Arginine-rich peptide motifs (ARMs) capable of binding unique RNA structures play
      critical roles in transcription, translation, RNA trafficking, and RNA packaging.
      Bacteriophage ARMs necessary for transcription antitermination bind to distinct
      boxB RNA hairpin sequences with a characteristic induced alpha-helical structure.
      Characterization of ARMs from lambdoid phages reveals that the dissociation
      constant of the P22 bacteriophage model-antitermination complex (P22(N21)
      P22boxB) is 200 +/- 56 pM in free solution at physiologic concentrations of
      monovalent cation, significantly stronger than previously determined by gel
      mobility shift and polyacrylamide gel coelectophoresis, and 2 orders of magnitude
      stronger than the tightest known native ARM-RNA interaction at physiological
      salt. Here, we use a reciprocal design approach to enhance the binding affinity
      of two separate alpha-helical ARM-RNA interactions; one derived from the native
      lambda phage antitermination complex and a second isolated using mRNA display
      selection experiments targeting boxB RNA.

PMID- 12224931
TI  - A practical catalytic asymmetric addition of alkyl groups to ketones.
AB  - Many catalysts will promote the asymmetric addition of alkylzinc reagents to
      aldehydes. In contrast, there are no reports of additions to ketones that are
      both general and highly enantioselective. We describe herein a practical
      catalytic asymmetric addition of ethyl groups to ketones. The catalyst is derived
      from reaction of camphor sulfonyl chloride and trans-1,2-diaminocyclohexane. The
      resulting diketone is reduced with NaBH4 to give the C2-symmetric exo
      diastereomer. Use of this ligand with titanium tetraisopropoxide and dialkylzinc
      at room temperature results in enantioselective addition of the alkyl group to
      the ketone. The resulting tertiary alcohols are isolated with high enantiomeric
      excess (all cases give greater than 87% ee, except one). The reaction has been
      run with 37 mmol (5 g) 3-methylacetophenone and 2 mol % catalyst to afford 73%
      yield of the resulting tertiary alcohol with 99% ee.

PMID- 12224932
TI  - A photochemical route for efficient cyclopeptide formation with a minimum of
      protection and activation chemistry.
AB  - An elaborated protocol is described which allows the efficient transformation of
      di-, tri-, and tetrapeptides into cyclopeptides with a minimum of protection and
      activation chemistry using the photoinduced electron transfer initiated
      decarboxylation of N-phthaloyl peptides resulting in C-C coupling between the
      initially formed carbon radicals.

PMID- 12224933
TI  - A negative temperature dependence of the electron self-exchange rates of zinc
      porphyrin pi radical cations.
AB  - The one-electron oxidation of ZnT(t-Bu)PP (T(t-Bu)PP2- = 5,10,15,20-tetrakis(3,5
      di-tert-butylphenyl)porphyrin dianion) by one equivalent of Ru(bpy)33+ (bpy =
      2,2'-bipyridine) results in quantitative formation of ZnT(t-Bu)PP*+ which is
      detected by ESR. In the presence of excess ZnT(t-Bu)PP, the ESR line width
      becomes broader with increasing ZnT(t-Bu)PP concentration due to the electron
      self-exchange between ZnT(t-Bu)PP*+ and ZnT(t-Bu)PP. The line width of the ESR
      signal of ZnT(t-Bu)PP*+ becomes broader as the temperature is decreased from 313
      to 233 K. This indicates that the electron self-exchange reaction becomes faster
      at a lower temperature. The substituent and solvent effects on such a negative
      temperature dependence of the electron self-exchange rates are reported.

PMID- 12224934
TI  - A metal-organic bilayer open framework with a dynamic component: single-crystal
      to-single-crystal transformations.
AB  - A metal-organic bilayered open framework, [Ni2(C26H52N10)]3[BTC]4.6C5H5N.36H2O
      (BOF-1, 1), has been prepared by the self-assembly of a new bismacrocyclic
      nickel(II) complex [Ni2(C26H52N10)(Cl)4].H2O (A) and sodium 1,3,5
      benzenetricarboxylate (Na3BTC) in the mixture of water/DMSO/pyridine. The X-ray
      crystal structure of 1 shows that 2D layers with the cavities of brick-wall
      motifs (22.6 x 14.3 A2) are formed by the coordination of the nickel(II) complex
      with BTC3- ions and that the two 2D layers are linked with the p-xylyl bridging
      groups of the bismacrocycles as pillars to generate 3D channels in the bilayered
      framework. The voids of the channels occupy 61% of the total volume, which are
      filled with pyridine and water guest molecules. When 1 was dried at 75 degrees C
      for 1.5 h, [Ni2(C26H52N10)]3[BTC]4.4H2O (2) resulted by maintaining the single
      crystallinity, which exhibited a dramatic decrease in the interlayer spacing as
      well as changes in the cell parameters. Solid 2 differentiates various alcohols
      such as MeOH, EtOH, isopropyl alcohol, and benzyl alcohol in toluene. When 1 was
      immersed in insoluble solvents such as pyridine and benzene, some guest molecules
      were exchanged with the aromatic molecules to give
      [Ni2(C26H52N10)]3[BTC]4.20pyridine.6H2O (3) and
      [Ni2(C26H52N10)]3[BTC]4.14benzene.19H2O (4), respectively. The guest-exchange
      processes also involve single-crystal-to-single-crystal transformation.

PMID- 12224935
TI  - A novel [2 + 2 + 1]/[2 + 1] tandem cycloaddition reaction of Fischer alkynyl
      carbenes with strained bicyclic olefins.
AB  - The reaction of strained bicyclic olefins with alkynyl carbenes and terminal
      olefins involves the creation of five new sigma C-C bonds with the concomitant
      formation of two new rings, thus creating a complex and densely functionalized
      structure in a single operation.

PMID- 12224936
TI  - Decreasing the ring size of a cyclic nonribosomal peptide antibiotic by in-frame
      module deletion in the biosynthetic genes.
AB  - Many natural products of therapeutical and biotechnological importance are
      nonribosomally synthesized peptides. Structural hallmarks of this class of
      compounds are the occurrence of unusual amino acids, mostly cyclic peptide
      backbones, and numerous further modifications such as acylation, heterocyclic
      ring formation, and glycosylation. Because of their structural complexity,
      chemical synthesis is usually an unattractive route to these molecules. In
      contrast, genetic engineering of the biosynthesis genes emerges as a potentially
      powerful approach to the combinatorial biosynthesis of useful analogues of the
      lead compounds. Nonribosomal peptide synthetases (NRPSs) carry out a sequential
      multistep assembly and modification of the peptides in a thiotemplate process
      described by the multiple carrier model. The modular architecture of NRPSs
      suggests straightforward methods for the reprogramming of these enzymes by
      exchange of catalytic subunits. However, many of the reported engineering
      attempts faced low product yields or even inactive hybrid enzymes. Using a new
      approach to obtain hybrid NRPSs, we show here that the deletion of an entire
      module in an NRPS assembly line caused the secretion of the predicted peptide
      antibiotic variant with a decreased ring size. Furthermore, a module exchange
      resulted in a significantly higher product yield than that observed in previous
      studies.

PMID- 12224937
TI  - Ethylene adsorption on platinum: kinetics, bonding, and relevance to catalysis.
AB  - Ethylene adsorption on platinum(111) single-crystal surfaces involves two states,
      a di-sigma species irreversibly bonded on the clean surface, and a second pi
      reversible adsorption which develops at high coverages. The two states display
      significantly different kinetic behavior, but they can slowly interchange. This
      suggests an adsorption mechanism at high coverages via an initial interaction
      with the few metal atoms left exposed by an imperfect monolayer followed by a
      collective rearrangement of the neighboring molecules into a new compressed
      layer.

PMID- 12224938
TI  - A new type of catalytic tandem 1,4-addition-aldol reaction which proceeds through
      an (oxa-pi-allyl)rhodium intermediate.
AB  - The reaction of 9-aryl-9-borabicyclo[3.3.1]nonanes (B-Ar-9BBN) with alpha,beta
      unsaturated ketones and aldehydes in the presence of 3 mol % [Rh(OMe)(cod)](2) in
      toluene at 20 degrees C for 2 h gave high yields of the tandem 1,4-addition-aldol
      reaction products with high syn selectivity. The reaction proceeds through the
      catalytic cycle consisting of 1,4-addition of an organorhodium species to an
      alpha,beta-unsaturated ketone and the aldol addition of the resulting (oxa-pi
      allyl)rhodium intermediate to an aldehyde.

PMID- 12224939
TI  - long-range charge transport in duplex DNA: anthraquinone sensitization results
      are independent of terminal ionic distribution.
AB  - Irradiation of an anthraquinone (AQ) derivative linked to a 5'-terminus of duplex
      DNA results in the formation of a base radical cation ("hole") that can migrate
      through the DNA. Reaction of the radical cation occurs primarily at the 5'-G of
      GG sequences. This reaction results in the formation of strand breaks when the
      irradiated DNA is treated with piperidine. The strand breaks are detected by
      polyacrylamide gel electrophoresis of samples that are labeled at the 3'- or 5'
      terminus with (32)P. In contrast to a previous report in which a linked rhodium
      metallointercalator is used as the sensitizer to oxidize the DNA (Williams, T.
      T.; Barton, J. K. J. Am. Chem. Soc. 2002, 124, 1840-1841), we find that the
      position of the label does not affect the relative reactivity of the GG steps
      when AQ is the sensitizer.

PMID- 12224940
TI  - Protease-catalyzed peptide synthesis on solid support.
AB  - The direct enzymatic synthesis of peptides from amino acids is widely used as a
      useful alternative to chemical synthesis. However, good yields of such enzyme
      catalyzed reactions require altered reaction conditions to overcome the bias for
      hydrolysis in aqueous medium. We argue that the synthesis/hydrolysis equilibrium
      can be shifted toward synthesis in aqueous medium by immobilizing the amine on
      solid support. In this report, we show the first examples of solid-phase peptide
      synthesis catalyzed by a protease in bulk aqueous buffer.

PMID- 12224941
TI  - [Ge(9)=Ge(9)=Ge(9)](6-): a linear trimer of 27 germanium atoms.
AB  - The title anion was synthesized by oxidation of nido-Ge94- with Ph3P or Ph3As in
      ethylenediamine solution. It was structurally characterized in the compound (Rb
      2,2,2-crypt)6[Ge9=Ge9=Ge9].3en (2,2,2-crypt = 4,7,13,16,21,24-hexaoxa-1,10
      diazabicyclo[8.8.8]hexacosane) crystallized from the solution. The anion is a
      linear trimer of nine-atom clusters with the shape of tricapped trigonal prisms
      elongated along two of the three prismatic edges. Each pair of clusters is
      connected by two exo-bonds.

PMID- 12224942
TI  - Resonance CARS study of the structure of "green" and "red" chromophores within
      the red fluorescent protein DsRed.
AB  - Vibrational spectra of red fluorescent protein DsRed have been studied for the
      first time by polarization-sensitive multiplex coherent anti-Stokes Raman
      scattering at two excitation wavelengths, 545 and 583 nm, in resonance with the
      absorption bands of the immature "green" and mature "red" protein chromophores.
      Overall vibrational patterns of both DsRed chromophores were found to be similar
      to each other and to differ from that of S65T-GFP at pH8. The combined analysis
      of our CARS data and published structural information suggest that both "green"
      and "red" DsRed species possess an extended chromophore structure. Consequently,
      our data suggest that pi-bonding system extension during isomerization around the
      cis peptide bond between Phe 65 and Gln 66 is a necessary but not sufficient step
      in DsRed chromophore maturation.

PMID- 12224943
TI  - Conformational memory in photodissociation of formic acid.
AB  - The trans and cis forms of formic acid (HCOOH) in solid argon favor essentially
      different photodissociation (193 nm) products, H2O + CO and H2 + CO2,
      respectively. The branching ratio of these channels differs between the two
      conformers by a factor of >10. The observed selective photodissociation features
      conformational memory when the transition state of a molecule is reached before
      torsional randomization. These data demonstrate that the photodissociation
      products can be efficiently steered with selective narrow-band infrared radiation
      promoting rotational isomerism, which makes a strong case of optically controlled
      chemical reactions

PMID- 12224944
TI  - Zwitterionic ring-borylated ansa-chromocene complexes.
AB  - Ring borylation of [Me4C2(eta5-C5H4)2CrCO] by B(C6F5)3 affords the zwitterionic
      complex {Me4(eta5-C5H4)(eta5-C4H3B(C6F5)3)}CrH(CO) (1), the first structurally
      characterized bent-metallocene complex of Cr(4+). This species decomposes
      thermally to the zwitterionic species {Me4(eta5-C5H4)(eta5-C4H3B(C6F5)3)}Cr (2)
      and the ionic species [Me4C2(eta5-C5H4)2CrCO][HB(C6F5)3] (3). The molecular
      structure of 2 is also described.

PMID- 12224945
TI  - Stereodivergent synthesis of all 15-F(2) isoprostanes.
AB  - Isoprostanes, lipid metabolites generated from free radical oxidation of membrane
      bound arachidonic acid, have been detected in organisms subjected to oxidative
      stress; however, the function and cellular targets of the isoprostanes are
      unclear. As an initial step toward studying the biological role of these
      molecules, we report the preparation of all known and anticipated 15-F2
      isoprostanes. The stereodivergent strategy to the complete isoprostane library
      features a ring-opening metathesis to introduce the cis-alkyl side chains that
      are characteristic of this class of molecules. Resolution to the individual
      stereoisomers can be accomplished by either a catalytic asymmetric reduction or
      an auxiliary-based separation protocol. In either case, the individual isomers
      can be converted to the corresponding 15-F2 isoprostanes through a
      straightforward functionalization of the carboxylic acid-containing side chain.
      The availability of this complete 15-F2 isoprostane library, containing both
      known and anticipated lipid metabolites, allows for the first time the side-by
      side evaluation of these compounds in a variety of biological assays.

PMID- 12224946
TI  - Crystal structure of a genomically encoded fosfomycin resistance protein (FosA)
      at 1.19 A resolution by MAD phasing off the L-III edge of Tl(+).
AB  - The fosfomycin resistance protein (FosA) catalyzes the Mn(II)- and K+-dependent
      addition of glutathione to the oxirane of the antibiotic fosfomycin. The crystal
      structure of FosA from Pseudomonas aeruginosa was solved at a resolution of 1.19
      A by multiwavelength anomalous diffraction at the L-III edge of a Tl+ derivative.
      The structure solution took advantage of the ability of Tl+ to substitute for K+.
      The existence of multiple Tl sites in the asymmetric unit suggests that this may
      be a generally useful technique for phasing protein crystal structures. A 1.35 A
      resolution structure with phosphate bound in the active site shows that the
      Mn(II) center has a rare four-coordinate geometry. The structure of the
      fosfomycin complex at 1.19 A resolution indicates that the Mn(II) center is close
      to five-coordinate with trigonal bipyramidal geometry and a ligand set consisting
      of two histidines (H7 and H64) and one phosphonate oxygen occupying the
      equatorial sites and the carboxylate of E110 at one of the apical sites. The
      oxirane oxygen of the substrate is located at the other apical site but is 0.2 A
      beyond the average Mn-O distance for five-coordinate Mn(II). The Mn(II) center is
      proposed to stabilize the alkoxide in the transition state, while the nearby
      hydroxyl group of T9 acts as a proton donor in the reaction. The K+ ion located
      6.5 A from the Mn(II) appears to help orient the substrate for nucleophilic
      attack.

PMID- 12224947
TI  - The active site of a zinc-dependent metalloproteinase influences the computed
      pK(a) of ligands coordinated to the catalytic zinc ion.
AB  - TNF-alpha converting enzyme (TACE) is a multidomain, membrane-anchored protein
      that includes a Zn-dependent protease domain. It releases the soluble form of
      cytokine tumor necrosis factor-alpha (TNF-alpha) from its membrane-bound
      precursor. TACE is a metalloprotease containing a catalytic glutamic acid, Glu
      406, and a Zn(2+) ion ligated to three imidazoles. The protonation states of the
      active site glutamic acid and inhibitors are important factors in understanding
      the potency of inhibitors with acidic zinc-ligating groups such as hydroxamic and
      carboxylic acids. Density functional methods were utilized to compute pK(a)
      values using a model of the catalytic site of TACE and to predict a concomitant
      mechanism of binding, consistent with lowering the pK(a) of the bound ligand and
      raising the pK(a) of the active site Glu-406. Weak acids, such as hydroxamic
      acids, bind in their neutral form and then transfer an acidic proton to Glu-406.
      Stronger acids, such as carboxylic acids, bind in their anionic form and require
      preprotonation of Glu-406. Similar binding events would be expected for other
      zinc-dependent proteases.

PMID- 12224948
TI  - FTIR spectra and normal-mode analysis of a tetranuclear manganese adamantane-like
      complex in two electrochemically prepared oxidation states: relevance to the
      oxygen-evolving complex of photosystem II.
AB  - The IR spectra and normal-mode analysis of the adamantane-like compound
      [Mn(4)O(6)(bpea)(4)](n+) (bpea = N,N-bis(2-pyridylmethyl)ethylamine) in two
      oxidation states, Mn(IV)(4) and Mn(III)Mn(IV)(3), that are relevant to the oxygen
      evolving complex of photosystem II are presented. Mn-O vibrational modes are
      identified with isotopic exchange, (16)O-->(18)O, of the mono-micro-oxo bridging
      atoms in the complex. IR spectra of the Mn(III)Mn(IV)(3) species are obtained by
      electrochemical reduction of the Mn(IV)(4) species using a spectroelectrochemical
      cell, based on attenuated total reflection [Visser, H.; et al. Anal. Chem. 2001,
      73, 4374-4378]. A novel method of subtraction is used to reduce background
      contributions from solvent and ligand modes, and the difference and double
      difference spectra are used in identifying Mn-O bridging modes that are sensitive
      to oxidation state change. Two strong IR bands are observed for the Mn(IV)(4)
      species at 745 and 707 cm(-1), and a weaker band is observed at 510 cm(-1). Upon
      reduction, the Mn(III)Mn(IV)(3) species exhibits two strong IR bands at 745 and
      680 cm(-1), and several weaker bands are observed in the 510-425 cm(-1) range. A
      normal-mode analysis is performed to assign all the relevant bridging modes in
      the oxidized Mn(IV)(4) and reduced Mn(III)Mn(IV)(3) species. The calculated force
      constants for the Mn(IV)(4) species are f(r)(IV)= 3.15 mdyn/A, f(rOr) = 0.55
      mdyn/A, and f(rMnr) = 0.20 mdyn/A. The force constants for the Mn(III)Mn(IV)(3)
      species are f(r)(IV)= 3.10 mdyn/A, f(r)(III)= 2.45 mdyn/A, f(rOr) = 0.40 mdyn/A,
      and f(rMnr) = 0.15 mdyn/A. This study provides insights for the identification of
      Mn-O modes in the IR spectra of the photosynthetic oxygen-evolving complex during
      its catalytic cycle.

PMID- 12224949
TI  - Structural characterization of a paramagnetic metal-ion-assembled three-stranded
      alpha-helical coiled coil.
AB  - A helical peptide designed to present an all-leucine core upon folding has been
      shown to exhibit concentration-dependent helicity and to exist as an ill-defined
      equilibrium population of oligomers. In marked contrast, an identical peptide
      covalently modified with a 2,2'-bipyridyl group at the N terminus forms a stable
      three-stranded parallel coiled coil in the presence of transition metal ions. We
      have employed paramagnetic Ni(2+) and Co(2+) ions to stabilize the trimeric
      assembly and to exploit their shift and relaxation properties in NMR structural
      studies. We find that metal-ion binding and helix-bundle folding are tightly
      coupled. Surprisingly, the three-helix bundle exhibits a dynamic N-terminal
      region, and a well-structured C-terminal half. The spectra indicate the presence
      of a dual conformation for the bundle extending from the N terminus to residue
      12. The structure of the two isomeric forms has been ascertained from
      interpretation of NOEs in the Ni(II) complex and (1)H pseudocontact shifts in the
      Co(II) complex. Two different facial isomers with distinct susceptibility tensors
      were identified. The bulky leucine side chain at position 3 in the peptide chain
      appears to play a role in the conformational variation at the N terminus.

PMID- 12224951
TI  - Long-range magnetization transfer between uncoupled nuclei by dipole-dipole cross
      correlated relaxation: a precise probe of beta-sheet geometry in proteins.
AB  - Interference between dipolar interactions in covalently linked (13)C-(1)H and
      nonlinked (1)H-(1)H pairs can be used to generate antiphase magnetization between
      noncoupled spins. The buildup rate of such antiphase terms is highly sensitive to
      local geometry, in particular the interproton distance and the (13)C-(1)H-(1)H
      internuclear angle. These rates have been measured for opposing C(alpha)H(alpha)
      pairs in antiparallel beta-sheets in the third Igg-binding domain of protein G
      (GB3) and in HIV protease, complexed with the inhibitor DMP323. For GB3, good
      agreement with the 1.1-A crystal structure is found. However, this agreement
      rapidly deteriorates with decreasing resolution of the corresponding X-ray
      structure. For HIV protease, two separate crystal structures that differ by less
      than 0.2 A from one another exhibit lower agreement in their predicted cross
      correlated relaxation rates relative to one another than is found between
      experimental rates and the average of the rates predicted for the two structures.
      These data indicate that quantitative measurement of these cross-correlated
      relaxation rates can provide highly accurate structural information in
      macromolecules.

PMID- 12224950
TI  - Influence of the distal his in imparting imidazolate character to the proximal
      his in heme peroxidase: (1)h NMR spectroscopic study of cyanide-inhibited his42-
      >ala horseradish peroxidase.
AB  - The functional higher oxidation states of heme peroxidases have been proposed to
      be stabilized by the significant imidazolate character of the proximal His. This
      is induced by a "push-pull" combination effect produced by the proximal Asp that
      abstracts ("pulls") the axial His ring N(delta)H, along with the distal
      protonated His that contributes ("pushes") a strong hydrogen bond to the distal
      ligand. The molecular and electronic structure of the distal His mutant of
      cyanide-inhibited horseradish peroxidase, H42A-HRPCN, has been investigated by
      NMR. This complex is a valid model for the active site hydrogen-bonding network
      of HRP compound II. The (1)H and (15)N NMR spectral parameters characterize the
      relative roles of the distal His42 and proximal Asp247 in imparting imidazolate
      character to the axial His. 1D/2D spectra reveal a heme pocket molecular
      structure that is highly conserved in the mutant, except for residues in the
      immediate proximity of the mutation. This conserved structure, together with the
      observed dipolar shifts of numerous active site residue protons, allowed a
      quantitative determination of the orientation and anisotropies of the
      paramagnetic susceptibility tensor, both of which are only minimally perturbed
      relative to wild-type HRPCN. The quantitated dipolar shifts allowed the factoring
      of the hyperfine shifts to reveal that the significant changes in hyperfine
      shifts for the axial His and ligated (15)N-cyanide result primarily from changes
      in contact shifts that reflect an approximately one-third reduction in the axial
      His imidazolate character upon abolishing the distal hydrogen-bond to the ligated
      cyanide. Significant changes in side chain orientation were found for the distal
      Arg38, whose terminus reorients to partially fill the void left by the
      substituted His42 side chain. It is concluded that 1D/2D NMR can quantitate both
      molecular and electronic structural changes in cyanide-inhibited heme peroxidase
      and that, while both residues contribute, the proximal Asp247 is more important
      than the distal His42 in imparting imidazole character to the axial His 170.

PMID- 12224952
TI  - A solid-phase approach to mouse melanocortin receptor agonists derived from a
      novel thioether cyclized peptidomimetic scaffold.
AB  - The solid-phase synthesis of a novel thioether cyclized peptidomimetic scaffold,
      displaying functionality at the i to i + 3 positions, is reported. The thioether
      bridge is formed on-bead by an intramolecular reaction between a chloroacetylated
      reduced peptide bond and the free thiol from a cysteine. The crude products were
      obtained in moderate to very high purity. A series of 19 compounds were prepared
      and tested for agonist activity at the mouse melanocortin receptors 1, 3, 4, and
      5 (mMC1-5R). From these results, several compounds were identified as having low
      micromolar agonist activity at the mMC1R and mMC4R. The former is involved in
      skin pigmentation and animal coat coloration. The latter is involved in the
      regulation of appetite and food intake and is currently a drug target for
      potential treatment of obesity. The most potent compound 1n with the
      pharmacophore motif "His-DPhe-Arg-Trp" was identified as having an EC(50) value
      of 165 nM at mMC1R, 7600 nM at mMC3R, 650 nM at mMC4R, and 335 nM at mMC5R. In
      addition, some of the compounds showed moderate selectivity for the mMC1R.

PMID- 12224953
TI  - A density functional study of O-O bond cleavage for a biomimetic non-heme iron
      complex demonstrating an Fe(v)-intermediate.
AB  - Density functional theory using the B3LYP hybrid functional has been employed to
      investigate the reactivity of Fe(TPA) complexes (TPA = tris(2
      pyridylmethyl)amine), which are known to catalyze stereospecific hydrocarbon
      oxidation when H(2)O(2) is used as oxidant. The reaction pathway leading to O-O
      bond heterolysis in the active catalytic species Fe(III)(TPA)-OOH has been
      explored, and it is shown that a high-valent iron-oxo intermediate is formed,
      where an Fe(V) oxidation state is attained, in agreement with previous
      suggestions based on experiments. In contrast to the analogous intermediate
      [(Por.)Fe(IV)=O](+1) in P450, the TPA ligand is not oxidized, and the electrons
      are extracted almost exclusively from the mononuclear iron center. The
      corresponding homolytic O-O bond cleavage, yielding the two oxidants Fe(IV)=O and
      the OH. radical, has also been considered, and it is shown that this pathway is
      inaccessible in the hydrocarbon oxidation reaction with Fe(TPA) and hydrogen
      peroxide. Investigations have also been performed for the O-O cleavage in the
      Fe(III)(TPA)-alkylperoxide species. In this case, the barrier for O-O homolysis
      is found to be slightly lower, leading to loss of stereospecificity and
      supporting the experimental conclusion that this is the preferred pathway for
      alkylperoxide oxidants. The difference between hydroperoxide and alkylperoxide as
      oxidant derives from the higher O-O bond strength for hydrogen peroxide (by 8.0
      kcal/mol).

PMID- 12224954
TI  - Helical rosette nanotubes with tunable chiroptical properties.
AB  - On the basis of transmission electron microscopy (TEM), dynamic light scattering
      (DLS), small-angle X-ray scattering (SAXS), and circular dichroism (CD) studies,
      compound 1 was shown to exist mainly in two states: (a) At high concentration (>
      or =1 mM, in methanol), 1 undergoes hierarchical self-assembly to generate
      rosette nanotubes with approximately 4 nm diameter and a concentration-dependent
      hydrodynamic radius in the range 10-100 nm. Under these conditions, addition of a
      chiral amino acid promoter (L-Ala), that binds to the crown ether moiety of 1 via
      electrostatic interactions, promotes a rapid transition (k(0) approximately equal
      0.48 s(-1), for [1] = 0.046 mM, [L-Ala] = 2.8 mM) from racemic to chiral rosette
      nanotubes with predefined helicities as indicated by the resulting induced
      circular dichroism (ICD). (b) At low concentration (< or =0.04 mM, in methanol),
      1 exists mainly in a nonassembled state as shown by TEM and DLS. Addition of L
      Ala in this case triggers a relatively slow (k(0) approximately equal 0.07 s(-1)
      for [1] = 0.04 mM, [L-Ala] = 2.4 mM) sequence of supramolecular reactions leading
      to the hierarchical self-assembly of rosette nanotubes with predefined
      helicities. Under both conditions a and b, the kinetic data unveiled the
      intrinsic ability of the rosette nanotubes to promote their own formation
      (autocatalysis). The degree of chiral induction was found to depend dramatically
      upon the chemical structure of the promoter. This process appears also to follow
      an all-or-none response, as the vast majority of the crown ether sites must be
      occupied with a promoter for a complete transition to chiral nanotubes to take
      place. Finally, both supramolecular pathways a and b offer an efficient approach
      for the preparation of helical rosette nanotubes with tunable chiroptical
      properties and may also be viewed as a process by which a predefined set of
      physical and chemical properties that characterizes a molecular promoter is
      expressed at the macromolecular level.

PMID- 12224955
TI  - Structure activity relationship by NMR and by computer: a comparative study.
AB  - There has recently been considerable interest in using NMR spectroscopy to
      identify ligand binding sites of macromolecules. In particular, a modular
      approach has been put forward by Fesik et al. (Shuker, S. B.; Hajduk, P. J.;
      Meadows, R. P.; Fesik, S. W. Science 1996, 274, 1531-1534) in which small ligands
      that bind to a particular target are identified in a first round of screening and
      subsequently linked together to form ligands of higher affinity. Similar
      strategies have also been proposed for in silico drug design, where the binding
      sites of small chemical groups are identified, and complete ligands are
      subsequently assembled from different groups that have favorable interactions
      with the macromolecular target. In this paper, we compare experimental and
      computational results on a selected target (FKBP12). The binding sites of three
      small ligands ((2S)1-acetylprolinemethylester, 1-formylpiperidine, 1
      piperidinecarboxamide) in FKBP12 were identified independently by NMR and by
      computational methods. The subsequent comparison of the experimental and
      computational data showed that the computational method identified and ranked
      favorably ligand positions that satisfy the experimental NOE constraints.

PMID- 12224956
TI  - Substituent effects on the bond dissociation enthalpies of aromatic amines.
AB  - Bond dissociation enthalpy differences, Z-X DeltaBDE = BDE(4-YC(6)H(4)Z-X) -
      BDE(C(6)H(5)Z-X), for Z = CH(2) and O are largely independent of X and are
      determined mainly by the stabilization/destabilization effect of Y on the 4
      YC(6)H(4)Z(*) radicals. The effects of Y are small (< or =2 kcal/mol for all Y)
      for Z = CH(2), but they are large for Z = O, where good correlations with
      sigma(p)(+)(Y) yield rho(+) = 6.5 kcal/mol. For Z = NH, two sets of
      electrochemically measured N-H DeltaBDEs correlate with sigma(p)(+)(Y), yielding
      rho(+) = 3.9 and 3.0 kcal/mol. However, in contrast to the situation with
      phenols, these data indicate that the strengthening effect on N-H BDEs of
      electron-withdrawing (EW) Y's is greater than the weakening effect of electron
      donating (ED) Y's. Attempts to measure N-H DeltaBDEs in anilines using two
      nonelectrochemical techniques were unsuccessful; therefore, we turned to density
      functional theory. Calculations on 15 4-YC(6)H(4)NH(2) gave N-H DeltaBDEs
      correlating with sigma(p)(+) (rho(+) = 4.6 kcal/mol) and indicated that EW and ED
      Y's had comparable strengthening and weakening effects, respectively, on the N-H
      bonds. To validate theory by connecting it to experiment, the N-H DeltaBDEs of
      four 4,4'-disubstituted diphenylamines and five 3,7-disubstituted phenothiazines
      were both calculated and measured by the radical equilibration EPR technique. For
      all compounds, theory and experiment agreed to better than 1 kcal/mol. Dissection
      of N-H DeltaBDEs in 4-substituted anilines and O-H DeltaBDEs in 4-substituted
      phenols into interaction enthalpies between Y and NH(2)/OH (molecule
      stabilization/destabilization enthalpy, MSE) and NH*/O* (radical
      stabilization/destabilization enthalpy, RSE) reveals that for both groups of
      compounds, ED Y's destabilize the molecule and stabilize the radical, while the
      opposite holds true for EW Y's. However, in the phenols the effects of
      substituents on the radical are roughly 3 times as great as those in the
      molecule, whereas in the anilines the two effects are of comparable magnitudes.
      These differences arise from the stronger ED character of NH(2) vs OH and the
      weaker EW character of NH* vs O*. The relatively large contributions to N-H BDEs
      in anilines arising from interactions in the molecules suggested that N-X
      DeltaBDEs in 4-YC(6)H(4)NH-X would depend on X, in contrast to the lack of effect
      of X on O-X and CH(2)-X DeltaBDEs in 4-YC(6)H(4)O-X and 4-YC(6)H(4)CH(2)-X. This
      suggestion was confirmed for X = CH(3), H, OH, and F, for which the calculated NH
      X DeltaBDEs yielded rho(+) = 5.0, 4.6, 4.0, and 3.0 kcal/mol, respectively.

PMID- 12224957
TI  - Syntheses of highly substituted enantiopure C6 and C7 enones(1).
AB  - Enantiopure epoxyvinyl sulfones SS-9a, SS-9b, produced from Jacobsen epoxidation
      of 2-phenylsulfonyl 1,3-cyclohexa- and cycloheptadiene, are used as a template
      for the construction of substituted cycloalkenones and as chiral synthetic
      equivalents of enones a and b. The addition of carbon nucleophiles to SS-9a, SS
      9b is high yielding and stereospecific. Enantiopure alpha,beta- and gamma
      substituted cycloalkenones are easily constructed using a variety of methods.

PMID- 12224958
TI  - Total syntheses of (+)-zampanolide and (+)-dactylolide exploiting a unified
      strategy.
AB  - The first total syntheses of (+)-zampanolide (1) and (+)-dactylolide (2), members
      of a new class of tumor cell growth inhibitory macrolides, have been achieved.
      Key features of the unified synthetic scheme included the stereocontrolled
      construction of the cis-2,6-disubstituted tetrahydropyran via a modified Petasis
      Ferrier rearrangement, a highly convergent assembly of the macrocyclic domain,
      and, in the case of zampanolide, a Curtius rearrangement/acylation tactic to
      install the N-acyl hemiaminal. The complete relative and absolute
      stereochemistries for both (+)-zampanolide and (+)-dactylolide were also
      assigned, albeit tentatively in the case of (+)-zampanolide (1).

PMID- 12224959
TI  - A high-throughput optical screening method for the optimization of colloidal
      water oxidation catalysts.
AB  - A high-throughput method has been developed for screening and optimization of
      colloidal water oxidation catalysts. The catalysts are irradiated in parallel by
      visible light from an overhead projector in solutions containing tris(2,2'
      bipyridyl)ruthenium(II) (Ru(bpy)(3)(2+)) and persulfate. The array of reaction
      solutions is held in a 96-well plate, and absorbance readings are taken
      intermittently using a bioassay plate reader. The absorbance at 430 nm is
      indicative of the amount of Ru(bpy)(3)(2+) remaining in solution. The best
      catalysts give the most persistent absorbance, because the oxygen evolution
      reaction is kinetically competitive with decomposition of Ru(bpy)(3)(3+). Reagent
      concentrations were varied using a factorial design-of-experiment approach in
      order to optimize reaction conditions for a IrO(2).xH(2)O colloidal catalyst. A
      higher colloid concentration, a lower Ru(bpy)(3)(2+) concentration, and a higher
      pH buffer doubled the number of turnovers relative to the original conditions.
      Metal oxide colloids consisting of IrO(2).xH(2)O doped with varying amounts of
      Pt, Ru, and Os were made using a parallel microwave synthesis technique and were
      tested both by the parallel screening method and by direct measurement of oxygen
      evolution. The correlation between the two methods was good, with Ir-Pt-Os oxide
      compositions showing the highest activity. The effect of adding small amounts of
      Pt and Os to IrO(2).xH(2)O appears to be predominantly to reduce the particle
      size of the colloids.

PMID- 12224960
TI  - Hybrid density functional theory studies on the magnetic interactions and the
      weak covalent bonding for the phenalenyl radical dimeric pair.
AB  - The phenalenyl radical (1) is a prototype of the hydrocarbon radical. Recently,
      the single crystal of 2,5,8-tri-tert-butylphenalenyl (2) was isolated and showed
      that the two phenalenyl radicals form a staggered dimeric pair, giving rise to
      strong antiferromagnetic interactions. The origin of the antiferromagnetic
      interactions and the nature of the chemical bond for the dimeric pair are
      challenging issues for chemists. First, spin-polarized hybrid DFT (Becke's half
      and half LYP (UB2LYP)) and CASSCF calculations were performed for 2 and its
      simplified model, the staggered-stacking phenalenyl radical dimeric pair (3a), to
      elucidate the origin of the strong antiferromagnetic coupling and the
      characteristics of the chemical bond. The calculated results showed that a SOMO
      SOMO overlap effect was responsible for the strong antiferromagnetic interactions
      and weak or intermediate covalent bonding between phenalenyl radicals. The tert
      butyl groups introduced at three beta-positions hardly affected the magnetic
      coupling, mainly causing steric hindrances in the crystalline state. Next, to
      obtain insight into ferromagnetic stacking, we investigated the stacking effect
      of staggered (3a)- and eclipsed (3b)-stacking phenalenyl radical dimeric pairs
      with a change of the SOMO-SOMO overlap on the basis of the extended McConnell
      model. We found that the stacking mode of the dimeric pair with both a small SOMO
      SOMO overlap and a ferromagnetic spin polarization effect provided a
      ferromagnetic coupling.

PMID- 12224961
TI  - Conformational analysis of a stereochemically complete set of cis-enediol peptide
      analogues.
AB  - A conformational analysis of a stereochemically complete set of peptide analogues
      based on a cis-enediol unit is presented. The cis-enediol unit, which can replace
      a two or a three amino acid segment of a peptide, contains two "side chains",
      four asymmetrical carbon atoms, and six free dihedral angles. To determine the
      accessible conformational space, the molecules are divided into three fragments,
      each containing two free dihedral angles. The energy surfaces are computed for
      all dihedral angle values, and the possible conformations of the cis-enediol unit
      analogues are built using all combinations of the surface minima. Such a "build
      up" procedure, which is very fast, is able to reproduce 75% of the minima
      obtained from a full dihedral angle exploration of the conformational space. The
      cis-enediol unit minima are compared with the corresponding di- and tripeptide
      minima; all peptide minima can be closely matched by a cis-enediol unit minimum
      of low energy (less than 2.2 kcal/mol above the lowest energy conformer).
      However, there are low energy minima of the cis-enediol unit that have no
      corresponding minima in peptides. The results are shown to depend strongly on the
      chirality of the analogues. The ability of each of the stereoisomers to mimic
      natural peptides, evaluated by the present approach, is correlated with its
      experimental activity in a renin inhibition assay.

PMID- 12224962
TI  - Proton-coupled electron transfer versus hydrogen atom transfer in benzyl/toluene,
      methoxyl/methanol, and phenoxyl/phenol self-exchange reactions.
AB  - Degenerate hydrogen atom exchange reactions have been studied using calculations,
      based on density functional theory (DFT), for (i) benzyl radical plus toluene,
      (ii) phenoxyl radical plus phenol, and (iii) methoxyl radical plus methanol. The
      first and third reactions occur via hydrogen atom transfer (HAT) mechanisms. The
      transition structure (TS) for benzyl/toluene hydrogen exchange has C(2)(h)()
      symmetry and corresponds to the approach of the 2p-pi orbital on the benzylic
      carbon of the radical to a benzylic hydrogen of toluene. In this TS, and in the
      similar C(2) TS for methoxyl/methanol hydrogen exchange, the SOMO has significant
      density in atomic orbitals that lie along the C-H vectors in the former reaction
      and nearly along the O-H vectors in the latter. In contrast, the SOMO at the
      phenoxyl/phenol TS is a pi symmetry orbital within each of the C(6)H(5)O units,
      involving 2p atomic orbitals on the oxygen atoms that are essentially orthogonal
      to the O.H.O vector. The transferring hydrogen in this reaction is a proton that
      is part of a typical hydrogen bond, involving a sigma lone pair on the oxygen of
      the phenoxyl radical and the O-H bond of phenol. Because the proton is
      transferred between oxygen sigma orbitals, and the electron is transferred
      between oxygen pi orbitals, this reaction should be described as a proton-coupled
      electron transfer (PCET). The PCET mechanism requires the formation of a hydrogen
      bond, and so is not available for benzyl/toluene exchange. The preference for
      phenoxyl/phenol to occur by PCET while methoxyl/methanol exchange occurs by HAT
      is traced to the greater pi donating ability of phenyl over methyl. This results
      in greater electron density on the oxygens in the PCET transition structure for
      phenoxyl/phenol, as compared to the PCET hilltop for methoxyl/methanol, and the
      greater electron density on the oxygens selectively stabilizes the
      phenoxyl/phenol TS by providing a larger binding energy of the transferring
      proton.

PMID- 12224963
TI  - The initial steps in the hydration of unsolvated peptides: water molecule
      adsorption on alanine-based helices and globules.
AB  - Equilibrium constants for the adsorption of the first water molecule onto a
      variety of unsolvated alanine-based peptides have been measured and Delta H
      degrees and DeltaS degrees have been determined. The studies were designed to
      examine the effects of conformation, charge, and composition on the propensity
      for peptides to bind water. In general, water adsorption occurs significantly
      more readily on the globular peptides than on helical ones: several of the singly
      charged helical peptides were not observed to adsorb a water molecule even at -50
      degrees C. These results place a limit on the free energy change for interaction
      between a water molecule and the helical peptide group. Molecular dynamics
      simulations reproduce most of the main features of the results. The ability to
      establish a network of hydrogen bonds to several different hydrogen-bonding
      partners emerges as a critical factor for strong binding of the water molecule.
      Whether the charge site is involved in water adsorption depends on how well it is
      shielded. Peptides containing a protonated histidine bind water much more
      strongly that those containing a protonated lysine because the delocalized charge
      on histidine is difficult to shield. The entropy change for adsorption of the
      first water molecule is correlated with the enthalpy change.

PMID- 12224964
TI  - Synthesis and properties of water-soluble asterisk molecules.
AB  - An asterisk is comprised of six semirigid arms projecting from a benzene nucleus.
      In the case at hand, asterisks were synthesized with one, two, or three aromatic
      rings (connected by sulfur atoms) in each of the six arms. A phosphomonoester at
      the termini of each arm solubilized the asterisks in water. The colloidal
      properties of these amphiphilic molecules were investigated by UV-vis and
      fluorescence spectroscopy, calorimetry, light scattering, surface tensiometry,
      and pulse-gradient spin-echo NMR. Solubility, solubilization, metal binding, and
      micelle "seeding" experiments were also carried out. Chain-conformation and
      supramolecular assembly into remarkable molecular "scrolls" were investigated by
      X-ray analysis and electron microscopy, respectively. One of the more interesting
      properties of the asterisks is that they remain monomeric in water despite having
      as many as 19 hydrophobic aromatic rings exposed to the water. The reasons for
      this behavior, and the possibility of exploiting it for constructing enzyme
      models free from aggregation equilibria, are discussed.

PMID- 12224965
TI  - Density functional theory study of redox pairs: 2. Influence of solvation and ion
      pair formation on the redox behavior of cyclooctatetraene and nitrobenzene.
AB  - A study of the electrochemical behavior of cyclooctatetraene (COT) and
      nitrobenzene with Density Functional Theory and the conductor like solvation
      model (COSMO) is reported. The two-electron reduction of the tub-shaped COT
      molecule is accompanied by a structural change to a planar structure of D(4)(h)()
      symmetry in the first electron addition step, and to a fully aromatic structure
      of D(8)(h)() symmetry in the second electron addition step. Theoretical models
      are examined that are aimed at understanding the electrolyte- and solvent
      dependent redox behavior of COT, in which a single 2e(-) redox wave is observed
      with KI electrolyte in liquid ammonia solution (DeltaDeltaE(disp) = [E(-2) - E(
      1)] - [E(-1) - E(0)] < 0, inverted potential), while two 1e(-) redox waves are
      observed (DeltaDeltaE(disp) > 0) with NR(4)(+)X(-) (R = butyl, propyl; X(-) =
      perchlorate) electrolyte in dimethylformamide solution. In all cases, the
      computed reaction energy profiles are in fair agreement with the experimental
      reduction potentials. A chemically intuitive theoretical square scheme method of
      energy partitioning is introduced to analyze in detail the effects of structural
      changes and ion-pair formation on the relative energies of the redox species. The
      structural relaxation energy for conversion of tub-COT to planar-COT is mainly
      apportioned to the first reduction step, and is therefore a positive contribution
      to DeltaDeltaE(disp). The effect of the structural change on the
      disproportionation energy for COT is counteracted by the substantially more
      positive reduction potential for planar-(COT)(-1) in comparison to tub-(COT)(-1).
      Ion pairing of alkali metal counterions with the anionic reduction products gives
      rise to a negative contribution to DeltaDeltaE(disp) because the second ion
      pairing step is more exothermic than the first, and the reduction of [KA] (A =
      COT, NB) is more exothermic than the reduction of A(-1). For COT, this negative
      energy differential term as a result of ion pairing predicts the experimentally
      observed inversion in the two 1e(-) potentials (DeltaDeltaE(disp) < 0).
      Nitrobenzene is treated with the same computational protocol to provide a system
      for comparison that is not complicated by the major structural change that
      influences the COT energy profile.

PMID- 12224966
TI  - "H/Vinyl" and "Alkyl/Vinyl" conical intersections leading to carbene formation
      from the excited states of cyclohexene and norbornene.
AB  - The photochemical [1,2]-shifts leading to carbene intermediates from cyclohexene
      and norbornene have been studied using CASSCF calculations and a 6-31G* basis
      set. In each case, a S(1)/S(0) conical intersection hyperline was identified that
      extends from the region of the reactant excited state to the carbene product. It
      is traditionally thought that the Rydberg R(pi,3s) state is responsible for
      carbene formation on photolysis of cyclic alkenes, but these new results indicate
      an efficient mechanism for carbene formation following excitation to the
      (1)(pipi*) state. This pathway is essentially barrierless and involves internal
      conversion to the ground-state surface via conical intersections between the
      excited zwitterionic valence state and the ground-state surface, similar to those
      responsible for cis-trans isomerization in ethene and other acyclic alkenes.
      These results are in excellent agreement with recent experimental data obtained
      using femtosecond spectroscopy.

PMID- 12224968
TI  - A novel approach for the sequential backbone assignment of larger proteins:
      selective intra-HNCA and DQ-HNCA.
AB  - Sequential assignment of backbone resonances in larger proteins can be achieved
      by recording two or more complementary triple-resonance NMR spectra of deuterated
      proteins. For such proteins, higher fields and experiments based on the TROSY
      method provide the needed resolution and sensitivity. However, increasingly rapid
      carbonyl relaxation at the high magnetic field strengths required by TROSY
      techniques renders assignment strategies that rely on sequential HN(CO)CA-type
      experiments much less efficient for proteins >40 kDa. Here we present two
      complementary new experiments, which allow backbone assignments with good
      sensitivity for larger deuterated proteins. A 3D intra-HNCA experiment provides
      uniquely the intraresidue connection, while a 3D DQ-HNCA experiment, which
      detects a (13)C(alpha)(i)()(13)C(alpha)(i-1)() double-quantum (DQ) coherence,
      contains the sequential information. The experiments work well at high magnetic
      fields, and their utility is demonstrated on a protein with a correlation time of
      28 ns ( approximately 60 kDa). For larger proteins the sensitivity is predicted
      through simulations which suggest that the approach should work for proteins with
      correlation times >50 ns.

PMID- 12224967
TI  - Factors affecting gas-phase deuterium scrambling in peptide ions and their
      implications for protein structure determination.
AB  - In this report, we evaluate the validity of using hydrogen/deuterium exchange in
      combination with collision-induced dissociation mass spectrometry (CID MS) for
      the detailed structural and conformational investigation of peptides and
      proteins. This methodology, in which partly deuterated peptide ions are subjected
      to collision-induced dissociation in the vacuum of a mass spectrometer, has
      emerged as a useful tool in structural biology. It may potentially provide
      quantitatively the extent of deuterium incorporation per individual amino acid in
      peptides and proteins, thus providing detailed structural information related to
      protein structure and folding. We report that this general methodology has
      limitations caused by the fact that the incorporated deuterium atoms migrate
      prior or during the CID MS analysis. Our data are focused on a variety of
      transmembrane peptides, incorporated in a lipid bilayer, in which the near
      terminal amino acids that anchor at the lipid-water interface are systematically
      varied. Our findings suggest that, under the experimental conditions we use, the
      extent of intramolecular hydrogen scrambling is strongly influenced by
      experimental factors, such as the exact amino acid sequence of the peptide, the
      nature of the charge carrier, and therefore most likely by the gas-phase
      structure of the peptide ion. Moreover, the observed scrambling seems to be
      independent of the nature of the peptide fragment ions (i.e., protonated B and Y'
      ' ions, and sodiated A and Y' ions). Our results strongly suggest that scrambling
      may be reduced by using alkali metal cationization instead of protonation in the
      ionization process.

PMID- 12224969
TI  - Relationships between carbocation stabilities and electrophilic reactivity
      parameters, E: quantum mechanical studies of benzhydryl cation structures and
      stabilities.
AB  - Quantum chemical calculations of the affinities of benzhydryl cations
      (XC(6)H(4))(2)CH(+) for the methyl anion, hydroxide, and hydride anion have been
      performed up to the B3LYP/6-311++G(3df,2pd)//B3LYP/6-31G(d,p) level and compared
      with rate and equilibrium constants in solution. An excellent linear correlation
      between the empirical electrophilicity parameter E (by log k = s(N + E); Mayr,
      H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.; Janker, B.; Kempf, B.; Loos,
      R.; Ofial, A. R.; Remennikov, R.; Schimmel, H. J. Am. Chem. Soc. 2001, 123, 9500
      9512) and the calculated methyl anion affinities ranging over 46.5 kcal mol(-1)
      is found that reproduces the electrophilicity parameters E which range from -10
      to +6 with a standard deviation of +/-0.26 (11 points). The calculated OH(-) and
      H(-) affinities correlate with the calculated CH(3)(-) affinities with a slope of
      1.00, indicating that the relative anion affinities of benzhydrylium ions are
      independent of the nature of the reference base. Linear correlations of the
      experimental pK((R)(+)) values and chloride ion affinities in solution with the
      calculated anion affinities in the gas phase indicate that solvation attenuates
      the differences of carbocation stabilization in the gas phase but does not affect
      the relative differences. Application of Marcus theory shows that only reaction
      series with alpha = partial differential DeltaG(++)/ partial differential
      Delta(r)G degrees = 0.5 corresponding to a slope parameter of s = 0.67 can have
      constant intrinsic barriers. The slope parameters s found for pi-nucleophiles and
      C-H hydride donors (s approximately equal 1) are interpreted by a decrease of the
      intrinsic barriers with increasing electrophilicities of the carbocations. On the
      other hand, a value of s < or = 0.67 as found for many n-nucleophiles as well as
      for Si-H, Ge-H, or Sn-H hydride donors is indicative of intrinsic barriers which
      are constant or slightly increase with increasing electrophilicity of the
      carbocation.

PMID- 12224970
TI  - Substituted polypyridine complexes of cobalt(II/III) as efficient electron
      transfer mediators in dye-sensitized solar cells.
AB  - A number of cobalt complexes of substituted polypyridine ligands were synthesized
      and investigated as possible alternatives to the volatile and corrosive
      iodide/triiodide redox couple commonly used as an electron-transfer mediator in
      dye-sensitized solar cells (DSSCs). The extinction coefficients in the visible
      spectrum are on the order of 10(2) M(-1) cm(-1) for the majority of these
      complexes, diminishing competition with the light-harvesting dye. Cyclic
      voltammetric studies revealed a dramatic surface dependence of the heterogeneous
      electron-transfer rate, which is surprisingly different for gold, carbon, and
      platinum electrodes. DSSCs were assembled using a mediator that consisted of a
      mixture of Co(II) and Co(III) complexes in a 10:1 ratio. DSSCs containing these
      mediators were used to characterize incident photon-to-current conversion
      efficiency and photoelectrochemical responses. The best performing of these
      mediators were identified and subjected to further study. As suggested by
      electrochemical results, gold and carbon are superior cathode materials to
      platinum, and no evidence of corrosion on any cathode material was observed.
      Addition of lithium salts to the mediator solution resulted in a dramatic
      improvement in cell performance. The observed Li(+) effect is explained in terms
      of the recombination of injected electrons in the photoanode with the oxidized
      mediator. The best mediator, based on tris(4,4'-di-tert-butyl-2,2'
      dipyridyl)cobalt(II/III) perchlorate, resulted in DSSCs exhibiting efficiencies
      within 80% of that of a comparable iodide/triiodide-mediated DSSC. Due to the
      commercial availability of the ligand and the simplicity with which the complex
      can be made, this new mediator represents a nonvolatile, noncorrosive, and
      practical alternative as an efficient electron-transfer mediator in DSSCs.

PMID- 12224973
TI  - Dermatitis factitia as a war weapon.

PMID- 12224972
TI  - Treatment of stage IA cutaneous T-Cell lymphoma with topical application of the
      immune response modifier imiquimod.

PMID- 12224974
TI  - Clindamycin for intraincisional antibiotic prophylaxis in dermatologic surgery.
AB  - OBJECTIVE: To assess the efficacy of intraincisional clindamycin therapy as an
      alternative to nafcillin treatment in decreasing the risk of postoperative wound
      infections in dermatologic surgery. DESIGN: Prospective, double-blinded,
      randomized, placebo-controlled trial conducted over a 7-month period. SETTING:
      Three private practice Mohs micrographic surgery referral centers. PATIENTS: A
      total of 1030 consecutive patients who underwent Mohs micrographic surgery with
      subsequent reconstruction. INTERVENTIONS: Prior to reconstruction, patients were
      randomly assigned to receive either intraincisional buffered lidocaine with
      epinephrine containing clindamycin or buffered lidocaine with epinephrine without
      clindamycin. Nurses and physicians who scored the wound at follow-up were blinded
      to the treatment conditions. MAIN OUTCOME MEASURES: Surgical wounds evaluated at
      the time of suture removal were scored according to a standardized assessment
      based on erythema, edema, and the presence of purulent discharge. Wounds scored 4
      or higher were considered to be infected. Bacterial cultures obtained when
      indicated were also compared. RESULTS: Of the 1172 surgical wounds included in
      the study, 29 had wound scores of 4 or higher, 6 in the study group and 23 in the
      control group (P =.001, Fisher exact test). Of these 29, 18 had culture-positive
      infections. Four of these occurred in the study group, and 14 occurred in the
      control group (P =.02, Fisher exact test). CONCLUSIONS: The results of this study
      further support the efficacy of single-dose preoperative intraincisional
      antibiotic treatment for dermatologic surgery. With the relatively high
      prevalence of patient-reported penicillin allergies, buffered lidocaine
      containing clindamycin offers an inexpensive, safe, convenient, and effective
      alternative.

PMID- 12224975
TI  - Treatment response of keloidal and hypertrophic sternotomy scars: comparison
      among intralesional corticosteroid, 5-fluorouracil, and 585-nm flashlamp-pumped
      pulsed-dye laser treatments.
AB  - OBJECTIVE: To compare the clinical response of keloidal and hypertrophic scars
      after treatment with intralesional corticosteroid alone or combined with 5
      fluorouracil (5-FU), 5-FU alone, and the 585-nm flashlamp-pumped pulsed-dye laser
      (PDL). DESIGN: Prospective, paired-comparison, randomized controlled trial.
      SETTING: A private ambulatory laser facility. PATIENTS: Ten patients with
      previously untreated keloidal or hypertrophic median sternotomy scars at least 6
      months after surgery that were considered problematic by the patients.
      INTERVENTIONS: Five segments were randomly treated with 4 different regimens: (1)
      laser radiation with a 585-nm PDL (5 J/cm(2)); (2) intralesional triamcinolone
      acetonide (TAC) (20 mg/mL); (3) intralesional 5-FU (50 mg/mL); and (4)
      intralesional TAC (1 mg/mL) mixed with 5-FU (45 mg/mL). One segment of each scar
      received no treatment and served as a control. MAIN OUTCOME MEASURES: Scar
      height, erythema, and pliability were evaluated before and every 8 weeks after
      treatment. Patients' subjective evaluations were tabulated. Histologic sections
      of segments were examined in 1 biopsy sample per segment at week 32. RESULTS:
      There was a statistically significant clinical improvement in all treated
      segments. No significant difference in treatment outcome vs method of treatment
      was noted. However, intralesional formulas resulted in faster resolution than the
      PDL: scar induration responded better to intralesional formulas, scar texture
      responded better to the PDL, and scar erythema responded the same as the control
      with all treatments. Adverse sequelae, including hypopigmentation,
      telangiectasia, and skin atrophy, were observed in 50% (5/10) of the segments
      that received corticosteroid intralesionally alone. No long-term adverse sequelae
      were demonstrated in the segments treated with other modalities. CONCLUSIONS:
      Clinical improvement of keloidal and hypertrophic scars after treatment with
      intralesional corticosteroid alone or combined with 5-FU, 5-FU alone, and PDL
      seemed comparable, with the exceptions of the incidence of adverse reactions,
      which were most common with intralesional corticosteroid. Intralesional 5-FU is
      comparable to the other therapies.

PMID- 12224976
TI  - Corticosteroid-sparing effect of intravenous immunoglobulin therapy in patients
      with pemphigus vulgaris.
AB  - BACKGROUND: Pemphigus vulgaris (PV) is a rare, potentially fatal autoimmune
      mucocutaneous blistering disease. The prolonged use of systemic corticosteroids,
      though clinically effective in high doses, can result in multiple debilitating
      adverse effects. Immunosuppressive agents, used as adjuvants and as
      corticosteroid-sparing agents, are not effective in all patients and are
      contraindicated in some. Therefore, alternative treatment modalities are needed
      to provide effective control of PV in such patients. OBJECTIVE: To demonstrate
      the corticosteroid-sparing effect of intravenous immunoglobulin (IVIg) therapy in
      patients with moderate to severe PV. DESIGN: A retrospective analysis in a cohort
      of 15 patients with moderate to severe PV who were treated with IVIg therapy. All
      15 patients were corticosteroid dependent, and the use of other systemic
      conventional immunosuppressive agents was contraindicated. The patients were
      followed up over a mean period of 6.2 years. SETTING: Ambulatory tertiary medical
      care facility of a university-affiliated hospital. INTERVENTION: All 15 patients
      received an IVIg dose of 1 to 2 mg/kg per cycle. MAIN OUTCOME MEASURES: The
      following information was documented in each of the 15 patients before and after
      the initiation of IVIg therapy: total dosage and total duration of prednisone
      therapy and number of relapses. Also, the highest dosage and adverse effects of
      prednisone therapy, as well as the total duration of observation, were recorded.
      RESULTS: All 15 patients had a satisfactory clinical response to IVIg therapy.
      The use of systemic prednisone was gradually discontinued over a mean period of
      4.3 months. A statistically significant difference was noted in the total dose of
      prednisone (P =.004), total duration of prednisone therapy (P =.003), and number
      of relapses (P<.001) before and after the initiation of IVIg therapy.
      CONCLUSIONS: Intravenous immunoglobulin therapy has a demonstrable corticosteroid
      sparing effect. It is a safe and effective alternative treatment modality in
      patients with PV who are dependent on systemic corticosteroids or who develop
      significant adverse effects as a result of their use.

PMID- 12224977
TI  - Efficacy of topical 5% imiquimod cream for the treatment of nodular basal cell
      carcinoma: comparison of dosing regimens.
AB  - OBJECTIVE: To establish a safe and efficacious dosing regimen for the treatment
      of primary nodular basal cell carcinoma (BCC) using 5% imiquimod cream. DESIGN:
      Two phase 2 studies were conducted: a 6-week, randomized, open-label, dose
      response study evaluating 4 dosing regimens and a 12-week, randomized, vehicle
      controlled, double-blind, dose-response study evaluating 4 dosing regimens.
      SETTING: Twenty-four public and private dermatology clinics in Australia and New
      Zealand (6-week study) and the United States (12-week study) participated.
      PATIENTS: The study populations comprised 99 patients enrolled in the 6-week
      study and 92 patients in the 12-week study. Patients were at least 18 years old
      and had a biopsy-confirmed diagnosis of nodular BCC. INTERVENTIONS: In the 6-week
      study, imiquimod was applied once daily for 3 or 7 days per week or twice daily
      for 3 or 7 days per week. In the 12-week study, imiquimod or placebo cream
      (vehicle) was applied once daily for 3, 5, or 7 days per week, or twice daily for
      7 days per week. The entire tumor area was excised 6 weeks after treatment and
      examined histologically for evidence of remaining BCC. MAIN OUTCOME MEASURE: The
      proportion of patients having no histologic evidence of BCC in the posttreatment
      excision specimen. RESULTS: Dosing once daily for 7 days per week resulted in the
      highest clearance rate, with 25 (71%) of 35 and 16 (76%) of 21 patients showing
      clearance of their tumor in the 6- and 12-week studies, respectively.
      CONCLUSIONS: Topical 5% imiquimod cream is well tolerated and most effective in
      treating nodular BCC when applied once daily for 7 days per week for either 12 or
      6 weeks.

PMID- 12224978
TI  - Frequency and severity of systemic disease in patients with subacute cutaneous
      lupus erythematosus.
AB  - OBJECTIVE: To compare the frequency and severity of systemic disease in patients
      with subacute cutaneous lupus erythematosus (SCLE) followed up in a dermatology
      practice vs patients with systemic lupus erythematosus (SLE) followed up in a
      rheumatology practice. DESIGN: Case-control comparison of patients matched for
      age, sex, and ethnicity. SETTING: University-affiliated dermatology and
      rheumatology practices. PATIENTS: Seventy-six patients with SCLE were compared
      with 24 patients with SLE. INTERVENTION: All medical records were reviewed and
      the patients were interviewed. MAIN OUTCOME MEASURES: Systemic and serologic
      findings were compared between patients with SCLE and those with SLE. RESULTS:
      Hematologic disorders were present in 6 patients (8%) with SCLE and in 13
      patients (54%) with SLE (P<.001). Serositis was present in 1 patient (1%) with
      SCLE and in 3 patients (12%) with SLE (P =.04). Renal involvement was present in
      12 patients (16%) with SCLE and in 6 patients (25%) with SLE (P =.36).
      Antinuclear antibodies were found in 52 patients (68%) with SCLE compared with 23
      patients (96%) with SLE (P =.006). Anti-Ro antibodies were found in 37 patients
      (49%) with SCLE compared with 10 patients (42%) with SLE (P =.64). Other
      serologic abnormalities (anti-native DNA, anti-Sm antibody, or anti-U(1)RNP) were
      present in 6 patients (8%) with SCLE compared with 15 patients (62%) with SLE
      (P<.001). Photosensitivity was present in 65 patients (86%) with SCLE, compared
      with 11 patients (46%) with SLE (P<.001). CONCLUSIONS: This analysis reveals a
      dissimilar frequency of internal organ involvement between patients with SCLE and
      SLE. Renal disease was similar in frequency and severity, and documented central
      nervous system involvement was rare in both groups.

PMID- 12224979
TI  - Botulinum a exotoxin for hyperfunctional facial lines: where not to inject.

PMID- 12224980
TI  - Analysis of cytokine expression in dermatology.
AB  - During the past decade, the detection of cytokines has been a focus of scientific
      interest, including in dermatology. Dysregulation of cytokine production seems to
      be involved in the pathogenesis of various diseases. The determination of
      cytokine levels is of increasing diagnostic importance, and cytokines are used as
      therapeutic agents too. Cytokines are polypeptides secreted by a wide variety of
      cells in response to diverse stimuli, and mediate autocrine, paracrine, or
      endocrine effects that are often pleiotropic and redundant. Their molecular
      weight lies between 6 and 70 kd. The cytokines of immunologic relevance are
      primarily those that are formed by immune cells (monokines and lymphokines)
      and/or influence their function. In principle, cytokines are detectable on 3
      levels: (1) By using polymerase chain reaction, the messenger RNA expression of
      cytokine genes can be detected and, with the newer techniques, even quantified.
      (2) Protein synthesis can be detected by using bioassays and enzyme immunoassays
      or immunocytologic or immunohistologic detection of intracellular cytokine
      production. (3) Finally, there are indirect methods for the detection of cytokine
      formation by analysis of products of cytokine activity. The immunobiological
      features of cytokines and the different approaches for cytokine determination are
      briefly discussed herein because basic knowledge of these biologically highly
      active messenger substances and the capabilities and limits of the individual
      detection methods are essential for a sensible interpretation of the relevant
      findings.

PMID- 12224981
TI  - Should the skin cancer examination be taught in medical school?
AB  - BACKGROUND: The fact that thin melanomas are associated with a greater than 95%
      survival rate, while later, more deeply invasive melanomas have a 5-year survival
      rate of less than 10%, demonstrates the potential personal and public health
      impact of early detection. The majority of patients with skin lesions are seen by
      nondermatologists who infrequently counsel patients about skin cancer prevention
      or perform a complete skin examination as part of routine care. We documented the
      antecedents of physician practice by evaluating medical students' observation,
      training, performance, and self-reported skill level for the skin cancer
      examination and sun protection counseling. METHODS: Surveys were administered and
      completed in classrooms and student workshops in each of the 4 medical school
      years during the spring of 1996 and 1997. We concentrate our analysis on the
      graduating fourth-year students. RESULTS: Of the 302 fourth-year students
      enrolled at Boston University School of Medicine, Boston, Mass, in 1996 and 1997,
      223 (74%) completed surveys. Among fourth-year students, 52% rated themselves as
      unskilled in skin cancer examinations. Twenty-eight percent of fourth-year
      students had never observed a skin cancer examination, 40% had received no
      training, and 35% had never practiced the examination. However, fourth-year
      students reporting at least 1 opportunity to observe, train, or practice an
      examination were 3 times as likely to report themselves as moderately to very
      skilled as students without such opportunities. CONCLUSION: If medical student
      training rates for the skin cancer examination are equally low elsewhere, as is
      likely, the present data suggest that even brief additions to the current
      curriculum, integrated into systems teaching, would augment student exposure and
      likely boost student skill levels.

PMID- 12224982
TI  - Cutaneous manifestations of hemophagocytic lymphohistiocytosis.
AB  - BACKGROUND: Hemophagocytic lymphohistiocytosis is a rare, rapidly progressive,
      and potentially fatal disorder of activated histiocytes. The initial clinical
      presentation commonly includes fever, hepatosplenomegaly, and pancytopenia. Skin
      eruptions are described in up to 65% of patients. Information regarding the
      morphological features, configuration, and distribution of these eruptions is
      lacking and is typically reported as nonspecific and "maculopapular." The aim of
      this report is to better delineate the cutaneous manifestations of the disorder
      to assist in differentiating the process from other systemic diseases.
      OBSERVATION: A case report of a neonate with hemophagocytic lymphohistiocytosis
      with generalized purpuric macules is described. The clinical features of 5 other
      patients with hemophagocytic lymphohistiocytosis at Children's Hospital of
      Wisconsin, Milwaukee, are summarized. Clinical images of 1 additional neonatal
      patient with hemophagocytic lymphohistiocytosis are presented as well. These
      observations demonstrate the varied cutaneous manifestations of hemophagocytic
      lymphohistiocytosis: erythroderma, generalized purpuric macules and papules, and
      morbilliform eruptions. CONCLUSION: Awareness of cutaneous involvement can assist
      in the initial diagnosis of hemophagocytic lymphohistiocytosis and potentially
      signify recurrences.

PMID- 12224983
TI  - Lentigo maligna with spread onto oral mucosa.
AB  - BACKGROUND: Lentigo maligna (LM) is a form of melanoma in situ most often seen in
      white patients on sun-exposed areas, primarily the head and neck. Spread of LM
      onto the conjunctiva has been reported. There have been no reports of LM
      extending onto oral mucosa. OBSERVATIONS: We report 4 cases of LM in white women
      with contiguous spread from perioral areas to oral mucosa. The locations of the
      primary lesions were the vermilion of the lip, vermilion and perioral skin,
      cheek, and cutaneous aspect of the lip. Three cases showed focal histopathologic
      evidence of invasion during the course of the disease. The lesions ran a
      prolonged course characterized by repeated recurrences after surgery. Three of
      the cases required a complicated reconstruction after surgical excision. Mohs
      surgery with rush permanent (paraffin-embedded) sections resulted in a long
      remission in 2 cases, while in 1 patient, treatment with carbon dioxide laser was
      unsuccessful. CONCLUSIONS: In a perioral distribution, LM can spread onto oral
      mucosa. This clinical presentation may cause significant long-term morbidity, as
      indicated by a high recurrence rate and/or progression to invasive melanoma. The
      oral mucosa should be examined in patients with atypical pigmented perioral
      lesions.

PMID- 12224984
TI  - The suitability of quality-of-life questionnaires for psoriasis research: a
      systematic literature review.
AB  - OBJECTIVE: To critically appraise the suitability of current quality-of-life
      (QOL) questionnaires for psoriasis research. DATA SOURCES: Computerized searches
      of 5 bibliographic databases. QUESTIONNAIRE SELECTION: Predefined criteria were
      used to identify QOL questionnaires in dermatologic studies. Two investigators
      independently assessed and agreed on multidimensional generic, dermatology
      specific, and psoriasis-specific QOL questionnaires for inclusion. DATA
      EXTRACTION: Data were extracted on the internal structure, reliability, and
      validity of the included questionnaires. DATA SYNTHESIS: Three generic, 3
      dermatology-specific, and none of the psoriasis-specific questionnaires met the
      inclusion criteria: the Nottingham Health Profile (NHP), the Medical Outcomes
      Study 36-Item Short Form Health Survey (SF-36), the Sickness Impact Profile
      (SIP), the Dermatology Quality of Life Scales (DQOLS), the Dermatology-Specific
      Quality of Life Instrument (DSQL), and the Skindex-29. The generic NHP, SF-36 and
      SIP are well established, reliable, and valid. Although the data are not
      conclusive, the SF-36 was useful to assess effects of psoriasis on its component
      scales. The dermatology-specific DQOLS, DSQL, and Skindex-29 are relatively new
      and, therefore, less widely tested. Available psychometric data demonstrated the
      reliability and validity of all 3 dermatology-specific questionnaires. The
      Skindex-29 was also useful to assess change. CONCLUSIONS: None of the identified
      psoriasis-specific questionnaires met the inclusion criteria. Data on the
      suitability of the included questionnaires for psoriasis research were relatively
      sparse. The included generic questionnaires allow comparisons with
      nondermatologic diseases but do not allow assessment of relevant dermatology
      specific aspects and are not sensitive to subtle effects of psoriasis on QOL. On
      the basis of the psychometric data of the present review, we find the Skindex-29
      to be the most valuable dermatology-specific questionnaire for psoriasis
      research. Combination of the Skindex-29 with the generic SF-36 combines the
      merits of both types of questionnaires and we therefore recommend this
      combination.

PMID- 12224986
TI  - Adverse cutaneous reactions to hydroxychloroquine are more common in patients
      with dermatomyositis than in patients with cutaneous lupus erythematosus.
AB  - BACKGROUND: Hydroxychloroquine sulfate and other antimalarial drugs have been
      used successfully as adjunctive therapy for patients with cutaneous lesions of
      dermatomyositis over the past 20 years. An increased incidence of cutaneous
      reactions to hydroxychloroquine has been postulated to occur in patients with
      dermatomyositis. OBJECTIVE: To determine if adverse cutaneous eruptions due to
      hydroxychloroquine are more common in patients with dermatomyositis than in those
      with cutaneous lupus erythematosus. DESIGN: Retrospective, age-, sex-, and race
      matched case-control study. SETTING: University-affiliated practice. PATIENTS:
      The study comprised 42 patients with dermatomyositis (39 adults) and 39 age-, sex
      , and race-matched adult patients with lupus erythematosus. MAIN OUTCOME
      MEASURES: Presence or absence of documented drug eruption due to
      hydroxychloroquine exposure. RESULTS: Of 39 patients, 12 (31%) with
      dermatomyositis developed a cutaneous reaction to hydroxychloroquine. Among age-,
      sex-, and race-matched patients with cutaneous lupus erythematosus, only 1
      developed a cutaneous reaction to hydroxychloroquine. None of the reactions
      observed in our patients resulted in serious morbidity or mortality.
      Additionally, 4 patients with dermatomyositis who reacted to hydroxychloroquine
      were treated with oral chloroquine phosphate, 2 of whom also reacted to
      chloroquine phosphate. CONCLUSIONS: When contemplating antimalarial therapy for
      dermatomyositis, both the physician and the patient should recognize that non
      life-threatening cutaneous reactions may occur in approximately one third of
      patients and that perhaps one half of those who react to hydroxychloroquine will
      also react to chloroquine.

PMID- 12224988
TI  - Adult vs childhood susceptibility to melanoma: is there a difference?

PMID- 12224989
TI  - Treatment of bullous pemphigoid with topical corticosteroids: review of a
      randomized controlled trial.

PMID- 12224990
TI  - Alefacept for psoriasis: promising drug, open questions.

PMID- 12224991
TI  - Caveat emptor (buyer beware).

PMID- 12224992
TI  - Giant tumor of the back.

PMID- 12224993
TI  - Vulvar lesion in a 45-year-old woman.

PMID- 12224994
TI  - Erythematous rash on the chest.

PMID- 12224995
TI  - Recurrent nodules on the feet of a child.

PMID- 12224997
TI  - Limitations in enzyme-linked immunosorbent assays for antibodies against
      desmogleins 1 and 3 in patients with pemphigus.

PMID- 12224996
TI  - The debate over diagnostic accuracy in melanoma: dermatologists or general
      practitioners?

PMID- 12224998
TI  - Darier sign: a historical note.

PMID- 12224999
TI  - Molecular and cellular pathogenesis of Spitz nevi.

PMID- 12225001
TI  - Treatment of bullous pemphigoid by low-dose methotrexate associated with short
      term potent topical steroids: an open prospective study of 18 cases.

PMID- 12225002
TI  - Pitfalls in clinical diagnosis of female carriers of X-linked hypohidrotic
      ectodermal dysplasia.

PMID- 12225003
TI  - Cutaneous drug eruption to infliximab: report of 4 cases with an interface
      dermatitis pattern.

PMID- 12225004
TI  - Significant systemic absorption of tacrolimus after topical application in a
      patient with lamellar ichthyosis.

PMID- 12225010
TI  - Phase transition in complex /psi/(4) theory.
AB  - Motivated by recent claims for rather unconventional first-order phase
      transitions in the two- and three-dimensional complex /psi/(4) theory in certain
      parameter ranges we performed Monte Carlo simulation studies of this model. From
      our results in two and three dimensions we can unambiguously conclude that there
      is no evidence for a first-order transition, provided the measure of field
      fluctuations is treated properly. The origin of the discrepancy is traced by
      comparative simulations reproducing the erroneous results and by a transfer
      matrix study of the one-dimensional case.

PMID- 12225011
TI  - Tuning the dipolar interaction in quantum gases.
AB  - We have studied the tunability of the interaction between permanent dipoles in
      Bose-Einstein condensates. Based on time-dependent control of the anisotropy of
      the dipolar interaction, we show that even the very weak magnetic dipole coupling
      in alkali gases can be used to excite collective modes. Furthermore, we discuss
      how the effective dipolar coupling in a Bose-Einstein condensate can be tuned
      from positive to negative values and even switched off completely by fast
      rotation of the orientation of the dipoles.

PMID- 12225012
TI  - BCS-BEC crossover in a gas of Fermi atoms with a Feshbach resonance.
AB  - We discuss the BCS-BEC crossover in a degenerate Fermi gas of two hyperfine
      states interacting close to a Feshbach resonance. We show that, by including
      fluctuation contributions to the free energy similar to that considered by
      Nozieres and Schmitt-Rink, the character of the superfluid phase transition
      continuously changes from the BCS-type to the BEC-type, as the threshold of the
      quasimolecular band is lowered. In the BEC regime, the superfluid phase
      transition is interpreted in terms of molecules associated with both the Feshbach
      resonance and Cooper pairing.

PMID- 12225013
TI  - High-sensitivity atomic magnetometer unaffected by spin-exchange relaxation.
AB  - Alkali-metal magnetometers compete with SQUID detectors as the most sensitive
      magnetic field sensors. Their sensitivity is limited by relaxation due to spin
      exchange collisions. We demonstrate a K magnetometer in which spin-exchange
      relaxation is completely eliminated by operating at high K density and low
      magnetic field. Direct measurements of the signal-to-noise ratio give a
      magnetometer sensitivity of 10 fT Hz(-1/2), limited by magnetic noise produced by
      Johnson currents in the magnetic shields. We extend a previous theoretical
      analysis of spin exchange in low magnetic fields to arbitrary spin polarizations
      and estimate the shot-noise limit of the magnetometer to be 2x10(-18) T Hz(-1/2).

PMID- 12225014
TI  - Thermal evolution and light curves of young bare strange stars.
AB  - We study numerically the cooling of a young bare strange star and show that its
      thermal luminosity, mostly due to e(+)e(-) pair production from the quark
      surface, may be much higher than the Eddington limit. The mean energy of photons
      far from the strange star is approximately 10(2) keV or even more. This differs
      both qualitatively and quantitatively from the thermal emission from neutron
      stars and provides a definite observational signature for bare strange stars. It
      is shown that the energy gap of superconducting quark matter may be estimated
      from the light curves if it is in the range from approximately 0.5 MeV to a few
      MeV.

PMID- 12225015
TI  - Three-wave interaction in a self-gravitating fluid.
AB  - Nonlinear three-wave interaction is investigated in rotating self-gravitating
      astrophysical fluids. Both direct and inverse cascades are found. The latter
      should be of importance for the formation of structures in rotating astrophysical
      objects like protogalaxies and galaxies. Linear gravitational instability is
      shown to be a process that develops on much longer time scales, compared to the
      nonlinear wave interaction, and the nonlinear precipitation of energy from the
      linearly unstable, slowly contracting mode towards smaller spatial and time
      scales is shown to be possible.

PMID- 12225016
TI  - High energy field theory in truncated anti-de Sitter space.
AB  - In this Letter we show that in five-dimensional anti-de Sitter (AdS) space
      truncated by boundary branes, effective field theory techniques are reliable at
      high energy (much higher than the scale suggested by the Kaluza-Klein mass gap),
      provided one computes suitable observables. We argue that in the model of Randall
      and Sundrum for generating the weak scale from the AdS warp factor, the high
      energy behavior of gauge fields can be calculated in a cutoff independent manner,
      provided one restricts Green's functions to external points on the Planck brane.
      Using the AdS/CFT (conformal field theory) correspondence, we calculate the one
      loop correction to the Planck brane gauge propagator due to charged bulk fields.
      These effects give rise to nonuniversal logarithmic energy dependence for a range
      of scales above the Kaluza-Klein gap.

PMID- 12225017
TI  - Resurrection of grand unified theory baryogenesis.
AB  - A "new" scenario is proposed for baryogenesis. We show that the delayed decay of
      colored Higgs particles in grand unified theories may generate an excess baryon
      number of the empirically desired amount, if the mass of the heaviest neutrino is
      in the range 0.02 eV<m(nu(3))<0.8 eV, provided that neutrinos are of the Majorana
      type. The scenario accommodates the case of degenerate neutrino masses, in
      contrast to the usual leptogenesis scenario, which does not work when three
      neutrino masses are degenerate.

PMID- 12225019
TI  - Large angle elastic alpha scattering on a N=Z nucleus above A=40.
AB  - Scattering of alpha particles from 44Ti, the lightest unstable alpha-particle
      nucleus above A=40, has been measured at backward angles. The "anomalous" order
      of-magnitude enhancement that is characteristic of 40Ca and other light alpha
      particle nuclei is not observed. Instead, the backward yield is similar to that
      observed for other nuclei heavier than 40Ca, and is well described with average
      optical model parameters.

PMID- 12225020
TI  - Enhancement of the electric dipole moment of the electron in PbO.
AB  - The a(1) state of PbO can be used to measure the electric dipole moment of the
      electron d(e). We discuss a semiempirical model for this state, which yields an
      estimate of the effective electric field on the valence electrons in PbO. Our
      final result is a lower limit on the measurable energy shift, which is
      significantly larger than was anticipated earlier: 2/W(d)/d(e)>or=2.4x10(25)
      Hz[d(e) divided by e cm].

PMID- 12225021
TI  - Ramsey-type spectroscopy with high-order harmonics.
AB  - We present an experiment where Ramsey-type spectroscopy is applied to
      autoionizing states of krypton by using the ninth harmonic (88 nm) of a
      femtosecond Ti:sapphire laser. The ionization process, detected by an electron
      energy spectrometer, shows the characteristic quantum interference pattern. The
      behavior of the fringe contrast compares favorably with a simple essential-state
      model, whose parameters have been taken from the literature. The experiment shows
      the feasibility of high-resolution spectroscopy in the extreme ultraviolet by
      using high-order laser harmonics.

PMID- 12225022
TI  - Orbital picture of ionization and its breakdown in nanoarrays of quantum dots.
AB  - We present exact numerical results indicating that ionization could be a useful
      tool to study electron correlations in artificial molecules and nanoarrays of
      metallic quantum dots. For nanorings consisting of Ag quantum dots of the type
      already fabricated, we demonstrate that the molecular orbital picture breaks down
      even for lowest energy ionization processes, in contrast to ordinary molecules.
      Our ionization results yield a transition point between localization and
      delocalization regimes in good agreement with various experimental data.

PMID- 12225023
TI  - Imaging and control of interfering wave packets in a dissociating molecule.
AB  - Using two identical 110 femtosecond (fs) optical pulses separated by 310 fs, we
      launch two dissociative wave packets in I2. We measure the square of the wave
      function as a function of both the internuclear separation, /Psi(R)/(2), and of
      the internuclear velocity, /Psi(v(R))/(2), by ionizing the dissociating molecule
      with an intense 20 fs probe pulse. Strong interference is observed in both
      /Psi(R)/(2) and in /Psi(v(R))/(2). The interference, and therefore the shape of
      the wave function, is controlled through the phase difference between the two
      dissociation pulses in good agreement with calculations.

PMID- 12225024
TI  - Observation of magnetoelectric directional anisotropy.
AB  - We report the first observation of a new optical phenomenon, magnetoelectric
      directional anisotropy (MEA). MEA is a polarization-independent anisotropy which
      occurs in crossed electric field E and magnetic field B perpendicular to the wave
      vector k of the light. It is described by a contribution to the refractive index
      of the form (delta)n=(gamma)k x E x B. Our experiment was performed on a
      Er(1.5)Y(1.5)Al(5)O(12) crystal, but MEA should exist in all media. The relation
      of this new effect with recently discovered magnetoelectric birefringence is
      discussed.

PMID- 12225025
TI  - Effect of a single quantum rotational excitation on state-to-state dynamics of
      the O(1D)+H2-->OH+H reaction.
AB  - Crossed molecular beams scattering experiments on the O(1D)+H2 reaction have been
      carried out in order to study the effect of the reagent (H2) rotational
      excitation on the detailed dynamics of this benchmark insertion reation.
      Experimental results indicate that a single quantum rotational excitation of H2
      has a significant impact on the product state distributions at the forward and
      backward scattering directions, while very little effect has been found in the
      sideway scattering direction. No clear patterns of this effect are found in the
      OH-product state distributions, indicating that the single quantum excitation on
      the dynamics is rather complicated.

PMID- 12225026
TI  - Capture and release of a conditional state of a cavity QED system by quantum
      feedback.
AB  - Detection of a single photon escaping an optical cavity QED system prepares a
      nonclassical state of the electromagnetic field. The evolution of the state can
      be modified by changing the drive of the cavity. For the appropriate feedback,
      the conditional state can be captured (stabilized) and then released. This is
      observed by a conditional intensity measurement that shows suppression of vacuum
      Rabi oscillations for the length of the feedback pulse and their subsequent
      return.

PMID- 12225018
TI  - Azimuthal anisotropy of K(0)(S) and Lambda+Lambda production at midrapidity from
      Au+Au collisions at sqrt[s(NN)]=130 GeV.
AB  - We report STAR results on the azimuthal anisotropy parameter v(2) for strange
      particles K(0)(S), Lambda, and Lambda at midrapidity in Au+Au collisions at
      sqrt[s(NN)]=130 GeV at the Relativistic Heavy Ion Collider. The value of v(2) as
      a function of transverse momentum, p(t), of the produced particle and collision
      centrality is presented for both particles up to p(t) approximately 3.0 GeV/c. A
      strong p(t) dependence in v(2) is observed up to 2.0 GeV/c. The v(2) measurement
      is compared with hydrodynamic model calculations. The physics implications of the
      p(t) integrated v(2) magnitude as a function of particle mass are also discussed.

PMID- 12225027
TI  - Adaptive homodyne measurement of optical phase.
AB  - We present an experimental demonstration of the power of feedback in quantum
      metrology, confirming the predicted [H. M. Wiseman, Phys. Rev. Lett. 75, 4587
      (1995)]] superior performance of an adaptive homodyne technique for single-shot
      measurement of optical phase. For measurements performed on weak coherent states
      with no prior knowledge of the signal phase, adaptive homodyne estimation
      approaches closer to the intrinsic quantum uncertainty than any previous
      technique. Our results underscore the importance of real-time feedback for
      reaching quantum limits in measurement and control.

PMID- 12225028
TI  - Collisions between optical spatial solitons propagating in opposite directions.
AB  - We formulate the theory describing the evolution and interactions between optical
      spatial solitons that propagate in opposite directions. We show that coherent
      collisions between counterpropagating solitons give rise to a new focusing
      mechanism resulting from the interference between the beams, and that
      interactions between such solitons are insensitive to the relative phase between
      the beams.

PMID- 12225029
TI  - Duality between the weak and strong interaction limits for randomly interacting
      fermions.
AB  - We establish the existence of a duality transformation for generic models of
      interacting fermions with two-body interactions. The eigenstates at weak and
      strong interaction U possess similar statistical properties when expressed in the
      U=0 and U= infinity eigenstates bases, respectively. This implies the existence
      of a duality point U(d) where the eigenstates have the same spreading in both
      bases. U(d) is surrounded by an interval of finite width which is characterized
      by a non-Lorentzian spreading of the strength function in both bases. Scaling
      arguments predict the survival of this intermediate regime as the number of
      particles is increased.

PMID- 12225030
TI  - Energy transmission in the forbidden band gap of a nonlinear chain.
AB  - A nonlinear chain driven by one end may propagate energy in the forbidden band
      gap by means of nonlinear modes. For harmonic driving at a given frequency, the
      process occurs at a threshold amplitude by sudden large energy flow that we call
      nonlinear supratransmission. The bifurcation of energy transmission is
      demonstrated numerically and experimentally on the chain of coupled pendula (sine
      Gordon and nonlinear Klein-Gordon equations) and sustained by an extremely simple
      theory.

PMID- 12225031
TI  - Dynamics of air avalanches in the access pit of an underground quarry.
AB  - Temperature measurements have been performed in the vertical access pit of an
      underground quarry. During autumn, air avalanches induce an initial thermal
      feedback and a stationary mixing state characterized by spatially coherent broad
      band fluctuations with a standard deviation of about 0.2 degrees C, linearly
      increasing with the inside-minus-outside temperature difference. Phase changes of
      water are shown to contribute to the onset condition, the feedback, and the
      stationary mixing state. This experiment may give insight on turbulent thermal
      and compositional convection with nonadiabatic boundaries.

PMID- 12225032
TI  - Topology of two-dimensional turbulence.
AB  - Velocity differences in the direct enstrophy cascade of two-dimensional
      turbulence are correlated with the underlying flow topology. The statistics of
      the transverse and longitudinal velocity differences are found to be governed by
      different structures. The wings of the transverse distribution are dominated by
      strong vortex centers, whereas the tails of the longitudinal differences are
      dominated by saddles. Viewed in the framework of earlier theoretical work, this
      result suggests that the transfer of enstrophy to smaller scales is accomplished
      in regions of the flow dominated by saddles.

PMID- 12225033
TI  - Uniqueness of reconstruction of multiphase morphologies from two-point
      correlation functions.
AB  - The restoration of the spatial structure of heterogeneous media, such as
      composites, porous materials, microemulsions, ceramics, or polymer blends from
      two-point correlation functions, is a problem of relevance to several areas of
      science. In this contribution we revisit the question of the uniqueness of the
      restoration problem. We present numerical evidence that periodic, piecewise
      uniform structures with smooth boundaries are completely specified by their two
      point correlation functions, up to a translation and, in some cases, inversion.
      We discuss the physical relevance of the results.

PMID- 12225034
TI  - Microscopic mechanisms of electric-field-induced alignment of block copolymer
      microdomains.
AB  - We investigate the microscopic mechanisms responsible for microdomain alignment
      in block copolymer solutions exposed to an electric field. Using time-resolved
      synchrotron small-angle x-ray scattering, we reveal two distinct processes, i.e.,
      grain boundary migration and rotation of entire grains, as the two dominant
      microscopic mechanisms. The former dominates in weakly segregating systems, while
      the latter is predominant in strongly segregated systems. The kinetics of the
      processes are followed as a function of polymer concentration and temperature and
      are correlated to the solution viscosity.

PMID- 12225035
TI  - Theory of diffusion controlled growth.
AB  - We present a new theoretical framework for diffusion limited aggregation and
      associated dielectric breakdown models in two dimensions. Key steps are
      understanding how these models interrelate when the ultraviolet cutoff strategy
      is changed, the analogy with turbulence and the use of logarithmic field
      variables. Within the simplest, Gaussian, truncation of mode-mode coupling, all
      properties can be calculated. The agreement with prior knowledge from simulations
      is encouraging, and a new superuniversality of the tip scaling exponent is both
      predicted and confirmed.

PMID- 12225036
TI  - Thermal contraction of au nanoparticles.
AB  - A fine Au powder, with a mean particle diameter of 4 nm, has been successfully
      fabricated. The crystalline structure of the 4 nm Au nanoparticles remains in fcc
      symmetry. No structural changes were found between 15 and 450 K. A crossover from
      a positive thermal expansion at low temperatures to a negative thermal expansion
      at high temperatures was observed in the fcc cell parameter at about 125 K.
      Anomalies associated with the crossover were also observed in the magnetic
      response and the heat capacity measurements. The observations can be reasonably
      well interpreted by accounting for the effects of the valence electron potential
      on the equilibrium lattice separations, with a weakly temperature dependent level
      spacing.

PMID- 12225037
TI  - Direct observation of tunneling in KDP using Neutron Compton scattering.
AB  - Neutron Compton scattering measurements presented here of the momentum
      distribution of hydrogen in KH2PO4 just above and well below the ferroelectric
      transition temperature are sufficiently sensitive to show clearly that the proton
      is coherent over both sites in the high temperature phase, a result that
      invalidates the commonly accepted order-disorder picture of the transition. The
      Born-Oppenheimer potential for the hydrogen, extracted directly from data for the
      first time, is consistent with neutron dif-fraction data, and the vibrational
      spectrum is in substantial agreement with infrared absorption measurements. The
      measurements are sensitive enough to detect the effect of surrounding ligands on
      the hydrogen bond, and can be used to study the systematic effect of the
      variation of these ligands in other hydrogen bonded systems.

PMID- 12225038
TI  - Highly extended image states around nanotubes.
AB  - We predict that freely suspended, linear molecular conductors or dielectrics,
      such as carbon nanotubes, can support electronic states that are localized far
      from the surface. These "tubular image states" are formed in extended potential
      wells resulting from the tug of war between the external electron's attraction to
      its image charge in the nanotube, and its repulsion from the tube due to its
      transverse angular momentum. The displacement of these states (>10 nm) away from
      the surface prevents their wave functions from collapsing, resulting in long
      lifetimes at low temperatures. We predict that tubular image states with binding
      energies of 1-10 meV can be formed via radiative recombination.

PMID- 12225039
TI  - Diffusion and reactions of hydrogen in F2-laser-irradiated SiO2 glass.
AB  - The diffusion and reactions of hydrogenous species generated by single-pulsed F2
      laser photolysis of SiO-H bond in SiO2 glass were studied in situ between 10 and
      330 K. Experimental evidence indicates that atomic hydrogen (H0) becomes mobile
      even at temperatures as low as approximately 30 K. A sizable number of H0
      dimerize by a diffusion-limited reaction into molecular hydrogen (H2) that may
      migrate above approximately 200 K. Activation energies for the diffusion,
      inherently scattered due to the structural disorder in glass, are separated into
      three bands centered at approximately 0.1 eV for free H0, approximately 0.2 eV
      presumably for shallow-trapped H0, and approximately 0.4 eV for H2.

PMID- 12225040
TI  - Liquid-liquid phase transition in elemental carbon: a first-principles
      investigation.
AB  - It has been recently suggested that elemental carbon may be a promising candidate
      to exhibit a liquid-liquid phase transition (LLPT). We report the results of
      first-principles molecular dynamics simulations showing no evidence of LLPT in
      carbon, in the same temperature and pressure range where such a transition was
      found using empirical calculations. Our simulations indicate a continuous
      evolution from a primarily sp-bonded liquid to an sp(2)-like and an sp(3)-like
      fluid, as a function of pressure, above the graphite melting line. The
      discrepancy between quantum and classical simulations is attributed to the
      inability of empirical potentials to describe complex electronic effects in
      condensed carbon phases.

PMID- 12225041
TI  - Nanostressors and the nanomechanical response of a thin silicon film on an
      insulator.
AB  - Pseudomorphic three-dimensional Ge nanocrystals (quantum dots) grown on thin
      silicon-on-insulator substrates can induce significant bending of the silicon
      template layer that is local on the nanometer scale. We use molecular dynamics
      simulations and analytical models to confirm the local bending of the Si template
      and to show that its magnitude approaches the maximum value for a freestanding
      membrane. The requisite greatly enhanced viscous flow of SiO2 underneath the Si
      layer is consistent with the dependence of the viscosity of SiO2 on shear stress.

PMID- 12225042
TI  - Experimental persistence probability for fluctuating steps.
AB  - The persistence behavior for fluctuating steps on the Si(111)
      (sqrt[3]xsqrt[3])R30 degrees -Al surface was determined by analyzing time
      dependent STM images for temperatures between 770 and 970 K. Using the standard
      persistence definition, the measured persistence probability displays power-law
      decay with an exponent of theta=0.77+/-0.03. This is consistent with the value of
      theta=3/4 predicted for attachment-detachment limited step kinetics. If the
      persistence analysis is carried out in terms of return to a fixed-reference
      position, the measured probability decays exponentially. Numerical studies of the
      Langevin equation used to model step motion corroborate the experimental
      observations.

PMID- 12225043
TI  - Contrasting friction and diffusion in molecularly thin confined films.
AB  - We study, using fluorescence correlation spectroscopy, translational diffusion in
      molecularly thin liquids confined within a surface forces apparatus. The
      diffusion coefficient decreases exponentially from the edges towards the center
      of the Hertzian contact and further suggests the presence of a small number of
      distinct diffusion processes. This holds alike a crystallizable fluid (OMCTS) and
      a glass-former (1,2-propane diol), both of which displayed static friction. We
      conclude that friction, the average of an ensemble of molecules, masked massively
      heterogeneous molecular mobility.

PMID- 12225044
TI  - Metallic mean-field stripes, incommensurability, and chemical potential in
      cuprates.
AB  - We perform a systematic slave-boson mean-field analysis of the three-band model
      for cuprates with first-principle parameters. Contrary to widespread belief based
      on earlier mean-field computations low doping stripes have a linear density close
      to 1/2 added hole per lattice constant. We find a dimensional crossover from 1D
      to 2D at doping approximately 0.1 followed by a breaking of particle-hole
      symmetry around doping 1/8 as doping increases. Our results explain in a simple
      way the behavior of the chemical potential, the magnetic incommensurability, and
      transport experiments as a function of doping. Bond centered and site-centered
      stripes become degenerate for small overdoping.

PMID- 12225045
TI  - Some generic aspects of bosonic excitations in disordered systems.
AB  - We consider noninteracting bosonic excitations in disordered systems, emphasizing
      generic features of quadratic Hamiltonians in the absence of Goldstone modes. We
      discuss relationships between such Hamiltonians and the symmetry classes
      established for fermionic systems. We examine the density rho(omega) of
      excitation frequencies omega, showing how the universal behavior rho(omega)
      approximately omega(4) for small omega can be obtained both from general
      arguments and by detailed calculations for one-dimensional models.

PMID- 12225046
TI  - Nonequilibrium transport through double quantum dots: Kondo effect versus
      antiferromagnetic coupling.
AB  - We theoretically study the nonequilibrium transport properties of double quantum
      dots, in both series and parallel configurations. Our results lead to novel
      experimental predictions that unambiguously signal the transition from a Kondo
      state to an antiferromagnetic spin-singlet state, directly reflecting the physics
      of the two-impurity Kondo problem. We prove that the nonlinear conductance
      through parallel dots directly measures the exchange constant J between the spins
      of the dots. In serial dots, the nonlinear conductance provides an upper bound on
      J.

PMID- 12225047
TI  - Wannier-Stark states in finite superlattices.
AB  - Individual Wannier-Stark states are resolved in a current experiment over a wide
      electric-field range for a 5 and 4 period finite superlattice utilizing a hot
      electron transistor. The observed field dependence of the tunneling transmission
      through the various states directly resembles the progressive localization of the
      wave functions. The basic transport through Wannier-Stark states in short-period
      superlattices is identified to be coherent. By tuning the Wannier-Stark state
      splitting with electric field into the optical phonon energy, the opening of new
      LO-phonon mediated transport paths is observed.

PMID- 12225048
TI  - Microwave resonance of the bubble phases in 1/4 and 3/4 filled high Landau
      levels.
AB  - We have measured the diagonal conductivity, sigma(xx), in the microwave regime of
      an ultrahigh mobility two dimensional electron system. We find a sharp resonance
      in Re[sigma(xx)] versus frequency when nu>4 and the partial filling of the
      highest Landau level, nu(*), is approximately 1/4 or 3/4 and temperatures <0.1 K.
      The resonance appears for a range of nu(*) from 0.20 to 0.38 and again from 0.64
      to 0.80. The peak frequency f(pk) changes from approximately 500 to approximately
      150 MHz as nu(*)=1/2 is approached. This range of f(pk) shows no dependence on nu
      where the resonance is observed. The quality factor, Q, of the resonance is
      maximum at about nu(*)=0.25 and 0.74. We interpret the resonance as due to a
      pinning mode of the bubble phase crystal.

PMID- 12225049
TI  - Finite-size effects in tunneling between parallel quantum wires.
AB  - We present theoretical calculations and experimental measurements which reveal
      finite-size effects in the tunneling between two parallel quantum wires,
      fabricated at the cleaved edge of a GaAs/AlGaAs bilayer heterostructure. Observed
      oscillations in the differential conductance, as a function of bias voltage and
      applied magnetic field, provide direct information on the shape of the confining
      potential. Superimposed modulations indicate the existence of two distinct
      excitation velocities, as expected from spin-charge separation.

PMID- 12225050
TI  - Direct comparison between potential landscape and local density of states in a
      disordered two-dimensional electron system.
AB  - The local density of states (LDOS) of the adsorbate-induced two-dimensional
      electron system (2DES) on n-InAs(110) is studied by scanning tunneling
      spectroscopy. In contrast to a similar 3DES, the 2DES LDOS exhibits 20 times
      stronger corrugations and rather irregular structures. Both results are
      interpreted as consequences of weak localization. Fourier transforms of the LDOS
      reveal that the k values of the unperturbed 2DES still dominate the 2DES, but
      additional lower k values contribute. To clarify the origin of the LDOS patterns,
      we measure the potential landscape of the 2DES area. We use it to calculate the
      expected LDOS and find reasonable agreement between calculation and experiment.

PMID- 12225051
TI  - Novel dynamical effects and persistent memory in phase separated manganites.
AB  - The time dependent response of the magnetic and transport properties of Fe-doped
      phase separated (PS) manganite La(0.5)Ca(0.5)MnO3 is reported. The nontrivial
      coexistence of ferromagnetic (FM) and non-FM regions induces a slow dynamics
      which leads to time relaxation and cooling rate dependence within the PS regime.
      This dynamics influences physical properties drastically. On one hand,
      metalliclike behavior, assumed to be a fingerprint of percolation, can be also
      observed before the FM phase percolates as a result of dynamical contributions.
      On the other hand, two novel effects for the manganites are reported, namely, the
      rejuvenation of the resistivity after aging and a persistent memory of low
      magnetic fields (<1 T), imprinted in the amount of the FM phase.

PMID- 12225052
TI  - First-order superconducting phase transition in CeCoIn5.
AB  - The superconducting phase transition in heavy fermion CeCoIn5 (T(c)=2.3 K in zero
      field) becomes first order when the magnetic field H parallel [001] is greater
      than 4.7 T, and the transition temperature is below T0 approximately 0.31T(c).
      The change from second order at lower fields is reflected in strong sharpening of
      both specific heat and thermal expansion anomalies associated with the phase
      transition, a strong magnetocaloric effect, and a steplike change in the sample
      volume. This effect is due to Pauli limiting in a type-II superconductor, and was
      predicted theoretically in the mid-1960s.

PMID- 12225053
TI  - Specific heat and thermal conductivity in the mixed state of MgB2.
AB  - The specific heat C and the electronic and phononic thermal conductivities
      kappa(e) and kappa(ph) are calculated in the mixed state for magnetic fields H
      near H(c2), including the effects of supercurrent flow and Andreev scattering.
      The resulting function C(H) is nearly linear while kappa(e)(H) exhibits an upward
      curvature near H(c2). The slopes decrease with impurity scattering which improves
      the agreement with the data on MgB2. The ratio of phonon relaxation times
      tau(n)/tau(s)=g(omega(0),H) for phonon energy omega(0) is smeared out around
      omega(0)=2Delta and tends to one for increasing H. This leads to a rapid
      reduction of kappa(ph)(H) in MgB2 for relatively small fields due to the rapid
      suppression of the smaller energy gap.

PMID- 12225054
TI  - Antiferromagnetism and hole pair checkerboard in the vortex state of high T(c)
      superconductors.
AB  - We propose a microscopic state for the vortex phase of BSCO superconductors.
      Around the vortex core or above H(c2), the d wave hole pairs form a checkerboard
      localized in the antiferromagnetic background. We discuss this theory in
      connection with recent STM experiments.

PMID- 12225055
TI  - Unstable flux flow due to heated electrons in superconducting films.
AB  - A flux instability occurs in superconductors at low temperatures, where e-e
      scattering is more rapid than e-ph, whereby the dissipation significantly
      elevates the electronic temperature while maintaining a thermal-like distribution
      function. The reduction in condensate and rise in resistivity produce a
      nonmonotonic current-voltage response. In contrast to the Larkin-Ovchinnikov
      instability where the vortex shrinks, in this scenario the vortex expands and the
      quasiparticle population rises. Measurements in Y(1)Ba(2)Cu(3)O(7-delta) agree
      quantitatively with the distinct predictions of this mechanism.

PMID- 12225056
TI  - Gap function with point nodes in borocarbide superconductor YNi2B2C.
AB  - To determine the superconducting gap function of YNi2B2C, the c-axis thermal
      conductivity kappa(zz) was measured in H rotated in various directions. The
      angular variation of kappa(zz) in H rotated within the ab plane shows a peculiar
      fourfold oscillation with narrow cusps. The amplitude of this fourfold
      oscillation becomes very small when H is rotated conically around the c axis with
      a tilt angle of 45 degrees. These results provide the first compelling evidence
      that the gap function has point nodes located along the a and b axes. This
      unprecedented gap structure challenges the current view on the pairing mechanism.

PMID- 12225057
TI  - Josephson junction through a thin ferromagnetic layer: negative coupling.
AB  - We investigate Josephson coupling through a ferromagnetic thin film using
      superconductor-insulator-ferromagnet-superconductor planar junctions. Damped
      oscillations of the critical current are observed as a function of the
      ferromagnetic layer thickness. We show that they result from the exchange energy
      gained or lost by a quasiparticle Andreev-reflected at the ferromagnet
      superconductor interface. The critical current cancels out at the transition from
      positive ("0") to negative ("pi") coupling, in agreement with theoretical
      calculations.

PMID- 12225058
TI  - Correlated defects, metal-insulator transition, and magnetic order in
      ferromagnetic semiconductors.
AB  - The effect of disorder on transport and magnetization in ferromagnetic III-V
      semiconductors, in particular (Ga,Mn)As, is studied theoretically. We show that
      Coulomb-induced correlations of the defect positions are crucial for the
      transport and magnetic properties of these highly compensated materials. We
      employ Monte Carlo simulations to obtain the correlated defect distributions.
      Exact diagonalization gives reasonable results for the spectrum of valence-band
      holes and the metal-insulator transition only for correlated disorder. Finally,
      we show that the mean-field magnetization also depends crucially on defect
      correlations.

PMID- 12225059
TI  - Quantum dimer model on the kagome lattice: solvable dimer-liquid and ising gauge
      theory.
AB  - We introduce quantum dimer models on lattices made of corner-sharing triangles.
      These lattices include the kagome lattice and can be defined in arbitrary
      geometry. They realize fully disordered and gapped dimer-liquid phase with
      topological degeneracy and deconfined fractional excitations, as well as solid
      phases. Using geometrical properties of the lattice, several results are obtained
      exactly, including the full spectrum of a dimer liquid. These models offer a very
      natural-and maybe the simplest possible-framework to illustrate general concepts
      such as fractionalization, topological order, and relation to Z2 gauge theories.

PMID- 12225060
TI  - Domain wall relaxation, creep, sliding, and switching in superferromagnetic
      discontinuous Co(80)Fe(20)/Al(2)O3 multilayers.
AB  - The ac susceptibility of a superferromagnetic discontinuous multilayer
      [Co(80)Fe20(1.4 nm)/Al(2)O3(3 nm)](10) is measured as a function of temperature,
      frequency, and field amplitude and compared to static and dynamic hysteresis
      loops. Its properties are successfully mapped onto the predicted [T. Nattermann,
      V. Pokrovsky, and V. M. Vinokur, Phys. Rev. Lett. 87, 197005 (2001)]] dynamical
      phase transitions, which link the relaxation, creep, sliding, and switching
      regimes of pinned domain walls.

PMID- 12225062
TI  - X-ray emission spectroscopy of hydrogen bonding and electronic structure of
      liquid water.
AB  - We use x-ray emission spectroscopy to examine the influence of the intermolecular
      interaction on the local electronic structure of liquid water. By comparing x-ray
      emission spectra of the water molecule and liquid water, we find a strong
      involvement of the a(1)-symmetry valence-orbital in the hydrogen bonding. The
      local electronic structure of water molecules, where one hydrogen bond is broken
      at the hydrogen site, is separately determined. Our results provide an
      illustration of the important potential of x-ray emission spectroscopy for
      elucidating basic features of liquids.

PMID- 12225061
TI  - Resonant electronic energy transfer from excitons confined in silicon
      nanocrystals to oxygen molecules.
AB  - We demonstrate efficient resonant energy transfer from excitons confined in
      silicon nanocrystals to molecular oxygen (MO). Quenching of photoluminescence
      (PL) of silicon nanocrystals by MO physisorbed on their surface is found to be
      most efficient when the energy of excitons coincides with triplet-singlet
      splitting energy of oxygen molecules. The dependence of PL quenching efficiency
      on nanocrystal surface termination is consistent with short-range resonant
      electron exchange mechanism of energy transfer. A highly developed surface of
      silicon nanocrystal assemblies and a long radiative lifetime of excitons are
      favorable for achieving a high efficiency of this process.

PMID- 12225063
TI  - High-fidelity quantum logic operations using linear optical elements.
AB  - Knill, Laflamme, and Milburn [Nature (London) 409, 46 ((2001))]] have shown that
      quantum logic operations can be performed using linear optical elements and
      additional ancilla photons. Their approach is probabilistic in the sense that the
      logic devices fail to produce an output with a failure rate that scales as 1/n,
      where n is the number of ancilla. Here we present an alternative approach in
      which the logic devices always produce an output with an intrinsic error rate
      that scales as 1/n(2), which may have several advantages in quantum computing
      applications.

PMID- 12225064
TI  - Quantum and classical correlations in quantum Brownian motion.
AB  - We investigate the entanglement properties of the joint state of a distinguished
      quantum system and its environment in the quantum Brownian motion model. This
      model is a frequent starting point for investigations of environment-induced
      superselection. Using recent methods from quantum information theory, we show
      that there exists a large class of initial states for which no entanglement will
      be created at all times between the system of salient interest and the
      environment. If the distinguished system has been initially prepared in a pure
      Gaussian state, then entanglement is created immediately, regardless of the
      temperature of the environment and the nonvanishing coupling.

PMID- 12225065
TI  - Distilling Gaussian states with Gaussian operations is impossible.
AB  - We show that no distillation protocol for Gaussian quantum states exists that
      relies on (i) arbitrary local unitary operations that preserve the Gaussian
      character of the state and (ii) homodyne detection together with classical
      communication and postprocessing by means of local Gaussian unitary operations on
      two symmetric identically prepared copies. This is in contrast to the finite
      dimensional case, where entanglement can be distilled in an iterative protocol
      using two copies at a time. The ramifications for the distribution of Gaussian
      states over large distances will be outlined. We also comment on the generality
      of the approach and sketch the most general form of a Gaussian local operation
      with classical communication in a bipartite setting.

PMID- 12225066
TI  - Gaussian transformations and distillation of entangled Gaussian states.
AB  - We prove that it is impossible to distill more entanglement from a single copy of
      a two-mode bipartite entangled Gaussian state via local Gaussian operations and
      classical communication. More generally, we show that any hypothetical
      distillation protocol for Gaussian states involving only Gaussian operations
      would be a deterministic protocol. Finally, we argue that the protocol considered
      by Eisert et al. [preceding Letter, Phys. Rev. Lett. 89, 137903 ()]] is the
      optimum Gaussian distillation protocol for two copies of entangled Gaussian
      states.

PMID- 12225068
TI  - Theory of rectification in tour wires: the role of electrode coupling.
AB  - We report first-principles studies of electronic transport and rectification in
      molecular wires attached to gold electrodes. Our ab initio calculation gives an
      accurate description of the voltage drop as well as the broadening and alignment
      of the molecular levels in the metal-molecule-metal complex. We find that the
      operation range and rectification in such strongly chemisorbed molecules is
      limited by the width of the transmission resonances and their proximity to the
      Fermi level.

PMID- 12225067
TI  - Period-doubling instability and memory in cardiac tissue.
AB  - Theoretical studies have indicated that alternans (period-doubling instability)
      of action potential duration is associated with a restitution relation with a
      slope >or=1. However, recent experimental findings suggest that the slope of the
      restitution relation is not necessarily predictive of alternans. Here, we
      compared a return map memory model to action potential data from an ionic model
      and found that the memory model reproduced dynamics that could not be explained
      by a unidimensional restitution relation. Using linear stability analysis, we
      determined the onset of the alternans in the memory model and confirmed that the
      slope of the restitution curve was not predictive.

PMID- 12225069
TI  - Comment on "Generation of electromagnetic pulses from plasma channels induced by
      femtosecond light strings".

PMID- 12225071
TI  - Comment on "Effect of hydrogen adsorption on the X-ray absorption spectra of
      small Pt clusters".

PMID- 12225073
TI  - Quantum hall states and boson triplet condensate for rotating spin-1 bosons.
AB  - We propose and analyze two series of clustered quantum Hall states for rotating
      systems of spin-1 bosons. The first series [labeled SU(4)(k)] includes the exact
      ground states of a model Hamiltonian at large angular momentum L, and also for
      N=3k particles at L=N. The latter is a spin-singlet boson-triplet condensate. The
      second series, labeled SO(5)(k), includes exact ground states at large L for
      different parameter values.

PMID- 12225074
TI  - Does a randall-sundrum scenario create the illusion of a torsion-free universe?
AB  - We consider spacetime with torsion in a Randall-Sundrum scenario where torsion,
      identified with the rank-2 Kalb-Ramond field, exists in the bulk together with
      gravity. While the interactions of both graviton and torsion in the bulk are
      controlled by the Planck mass, an additional exponential suppression comes for
      the torsion zero-mode on the visible brane. This may serve as a natural
      explanation of why the effect of torsion is so much weaker than that of curvature
      on the brane. The massive torsion modes, on the other hand, are correlated with
      the corresponding gravitonic modes and may be detectable in TeV-scale
      experiments.

PMID- 12225075
TI  - Positive mass from holographic causality.
AB  - For (n+1)-dimensional asymptotically anti-de Sitter (AdS) spacetimes which have
      holographic duals on their n-dimensional conformal boundaries, we show that the
      imposition of causality on the boundary theory is sufficient to prove positivity
      of mass for the spacetime when n> or =3, without the assumption of any local
      energy condition. We make crucial use of a time-delay formula relating the
      Ashtekar-Magnon mass of the spacetime to the time delay of a bulk null curve
      relative to that of a boundary null geodesic. We also discuss holographic
      causality for the negative mass AdS soliton and its implications for the positive
      energy conjecture of Horowitz and Myers.

PMID- 12225076
TI  - Additional stringy sources for electric dipole moments.
AB  - We show that string models with low energy supersymmetry which accommodate the
      fermion mass hierarchy generally give nonuniversal soft trilinear couplings (A
      terms). In conjunction with the apparently large Cabibbo-Kobayashi-Maskawa (CKM)
      phase, this results in large fermion electric dipole moments (EDMs) even in the
      absence of CP violating phases in the supersymmetry breaking auxiliary fields and
      the micro term. Nonobservation of the EDMs therefore implies that strings select
      special flavor and/or supersymmetry breaking patterns.

PMID- 12225078
TI  - Transverse-momentum fluctuations in pi(+)p and K(+)p Collisions at 250 GeV/c.
AB  - We report results on event-by-event fluctuations of transverse momentum,
      Phi(p(t)), in pi(+)p and K(+)p collisions at 250 GeV/c. For the first time, their
      dependence on rapidity region, transverse momentum acceptance, multiplicity, mean
      transverse momentum per event, and on the correlation between transverse momentum
      and multiplicity are systematically presented. The results are compared with
      those from the PYTHIA Monte Carlo generator. The fluctuations under the same
      acceptance cuts as used in current heavy-ion experiments are also presented.

PMID- 12225077
TI  - Dalitz plot analysis of the decay D(+)-->K(-)pi(+)pi(+) and indication of a low
      mass scalar Kpi resonance.
AB  - We study the Dalitz plot of the decay D(+)-->K(-)pi(+)pi(+) with a sample of
      15090 events from Fermilab experiment E791. Modeling the decay amplitude as the
      coherent sum of known Kpi resonances and a uniform nonresonant term, we do not
      obtain an acceptable fit. If we allow the mass and width of the K(*)(0)(1430) to
      float, we obtain values consistent with those from PDG but the chi(2) per degree
      of freedom of the fit is still unsatisfactory. A good fit is found when we allow
      for the presence of an additional scalar resonance, with mass 797+/-19+/-43
      MeV/c(2) and width 410+/-43+/-87 MeV/c(2). The mass and width of the
      K(*)(0)(1430) become 1459+/-7+/-5 MeV/c(2) and 175+/-12+/-12 MeV/c(2),
      respectively. Our results provide new information on the scalar sector in hadron
      spectroscopy.

PMID- 12225080
TI  - Leading-particle effect from heavy-quark recombination.
AB  - The leading particle effect in charm hadroproduction is an enhancement of the
      cross section for a charmed hadron D in the forward direction of the beam when
      the beam hadron has a valence parton in common with the D. The large D(+)/D(-)
      asymmetry observed by the E791 experiment is an example of this phenomenon. We
      show that the heavy-quark recombination mechanism provides an economical expla
      nation for this effect. In particular, the D(+)/D(-) asymmetry can be fit
      reasonably well using a single parameter whose value is consistent with a recent
      determination from charm photoproduction.

PMID- 12225081
TI  - Is there a significant excess in bottom hadroproduction at the tevatron?
AB  - We discuss the excess in the hadroproduction of B mesons at the Tevatron. We show
      that an accurate use of up-to-date information on the B fragmentation function
      reduces the observed excess to an acceptable level. Possible implications for
      experimental results reporting bottom quark cross sections, also showing an
      excess with respect to next-to-leading order theoretical predictions, are
      discussed.

PMID- 12225082
TI  - Strong coupling constant from the photon structure function.
AB  - We extract the value of the strong coupling constant alpha(s) from a single
      parameter pointlike fit to the photon structure function F(gamma)(2) at large x
      and Q(2) and from a first five-parameter full (pointlike and hadronic) fit to the
      complete F(gamma)(2)data set taken at PETRA, TRISTAN, and LEP. In next-to-leading
      order and the MS renormalization and factorization schemes, we obtain
      alpha(s)(m(Z))=0.1183+/-0.0050(expt)(+0.0029)(-0.0028)(theor) (pointlike) and
      alpha(s)(m(Z))=0.1198+/-0.0028(expt)(+0.0034)(-0.0046)(theor) (pointlike and
      hadronic). We demonstrate that the data taken at LEP have reduced the
      experimental error by about a factor of 2, so that a competitive determination of
      alpha(s) from F(gamma)(2) is now possible.

PMID- 12225083
TI  - Quantum theory of spontaneous emission by real moving atoms.
AB  - We outline the solution of a fundamental problem in quantum theory which has
      hitherto lacked a proper solution, namely, finding the requisite quantum
      theoretical framework guaranteeing that the calculated inverse spontaneous
      emission rate of a moving atom, as a composite system of charged particles
      interacting with the Maxwell field, is slowed down exactly as in time dilation.

PMID- 12225084
TI  - Unified treatment of positron annihilation and positronium formation.
AB  - The effects of the positron (e(+)) annihilation in e(+) scattering by the H atom
      are included directly in the Hamiltonian as an absorption potential, and hence
      the finite lifetimes Gamma(ns) of positronium (Ps) in states ns are automatically
      taken account of. The Schrodinger equation is solved using the hyperspherical
      close-coupling method. The annihilation and Ps formation are shown to be
      inseparable near the Ps(1s) threshold E(th); Ps formation constitutes just an
      indirect pathway to annihilation. The annihilation cross section, which would
      diverge near E(th) if Gamma(1s) were infinite, connects smoothly across E(th) to
      the cross section for Ps formation, which is meaningful only at energies well
      above E(th).

PMID- 12225079
TI  - Observation of the decay B(0)-->D(+/-)D(*-/+).
AB  - We report the first observation of the decay B(0)-->D(+/-)D(*-/+) with the Belle
      detector at the KEKB e(+)e(-) Collider operated at the Upsilon(4S) resonance. The
      sum of branching fractions B(B(0)-->D(+)D(*-))+B(B(0)-->D(-)D(*+)) is measured to
      be (1.17+/-0.26(+0.22)(-0.25))x10(-3) using the full reconstruction method where
      both charmed mesons from B0 decays are reconstructed. A consistent value [(1.48+/
      0.38(+0.28)(-0.31))x10(-3)] is obtained using a partial reconstruction technique
      that uses only the slow pion from the D(*-)-->D(-0)pi(-) decay and a fully
      reconstructed D(+) to reconstruct the B(0).

PMID- 12225085
TI  - Overcoming the diffraction limit in wave physics using a time-reversal mirror and
      a novel acoustic sink.
AB  - In recent years, time-reversal (TR) mirrors have been developed that create TR
      waves for ultrasonic transient fields propagating through complex media. A TR
      wave back propagates and refocuses exactly at its initial source. However,
      because of diffraction, even if the source is pointlike the wave refocuses on a
      spot size that cannot be smaller than half a wavelength. Here, by using a TR
      interpretation of this limit, we show that this latter limitation can be overcome
      if the source is replaced by its TR image. This new device acts as an acoustic
      sink that absorbs the TR wave. Here we report the first experimental result
      obtained with an acoustic sink where a focal spot size of less than 1/14th of one
      wavelength is recorded.

PMID- 12225086
TI  - Universal spectrum of two-dimensional turbulence on a rotating sphere and some
      basic features of atmospheric circulation on giant planets.
AB  - The Kolmogorov-Batchelor-Kraichnan (KBK) theory of two-dimensional turbulence is
      generalized for turbulence on the surface of a rotating sphere. The energy
      spectrum develops considerable anisotropy; a steep -5 slope emerges in the zonal
      direction, while in all others the classical KBK scaling prevails. This flow
      regime in robust steady state is reproduced in simulations with linear drag. The
      conditions favorable for this regime may be common for giant planets' atmospheric
      circulations; the same steep spectra are found in their observed zonal velocity
      profiles and utilized to explain their basic characteristics.

PMID- 12225087
TI  - Universality of small scale turbulence.
AB  - The proposed universality of small scale turbulence is investigated for a set of
      measurements in a cryogenic free jet with a variation of the Reynolds number (Re)
      from 8500 to 10(6) (max(R(lambda) approximately 1200). The traditional analysis
      of the statistics of velocity increments by means of structure functions or
      probability density functions is replaced by a new method which is based on the
      theory of Markov processes. It gives access to a more complete characterization
      by means of joint probabilities of finding velocity increments at several scales.
      Based on this more comprehensive method, our results are very far from a possible
      universal state, even for R(lambda) above 1000.

PMID- 12225088
TI  - Evolution of a dust void in a radio-frequency plasma sheath.
AB  - The onset and growth of a dust void are investigated in a radio-frequency (rf)
      sheath of a capacitively coupled argon plasma. A circularly symmetric void
      emerges and grows with increasing rf power and pressure in the central region of
      the dust cloud levitating in the sheath. Experimental measurements of the void
      diameter are compared with the predictions of a simple phenomenological theory,
      based on a balance of forces on dust grains.

PMID- 12225089
TI  - Dynamical overstability of radiative blast waves: the atomic physics of shock
      stability.
AB  - Atomic-physics calculations of radiative cooling are used to develop criteria for
      the overstability of radiating shocks. Our calculations explain the measurement
      of shock overstability by Grun et al. [Phys. Rev. Lett. 66, 2738 (1991)]] and
      explain why the overstability was not observed in other experiments. The
      methodology described here can be especially useful in astrophysical situations
      where the relevant properties leading to an overstability can be measured
      spectroscopically, but the effective adiabatic index is harder to determine.

PMID- 12225090
TI  - High-beta equilibria of drift-optimized compact stellarators.
AB  - Compact stellarator configurations have been obtained with good neoclassical
      confinement that are stable to both pressure- and current-driven modes for high
      values of beta. These configurations are drift-optimized tokamak-stellarator
      hybrids with a high-shear tokamak-like rotational transform profile and /B/ that
      is approximately poloidally symmetric. The bootstrap current is consistent with
      the required equilibrium current and, while larger than that in existing
      stellarators, is typically only a small fraction (1/3-1/5) of that in an
      equivalent tokamak. These configurations have strong magnetic wells and
      consequently high interchange stability beta limits up to beta=23%. Because of
      the reduced bootstrap current, these configurations are stable to low-n ideal MHD
      kink modes with no wall stabilization for values of beta ( approximately 7%-11%)
      significantly larger than in an equivalent advanced tokamak.

PMID- 12225091
TI  - Collective deceleration of relativistic electrons precisely in the core of an
      inertial-fusion target.
AB  - The energy deposition of a relativistic electron beam in a plasma can be managed
      through turning on or off fast beam-plasma instabilities in desirable regions.
      This management may enable new ways of realizing the fast-igniter scenario of
      inertial fusion. Collisional effects alone can decelerate electrons of at most a
      few MeV within the core of an inertial-fusion target. Beam-excited Langmuir
      turbulence, however, can decelerate even ultrarelativistic electrons in the core.

PMID- 12225092
TI  - Short wavelength temperature gradient driven modes in tokamak plasmas.
AB  - New unstable temperature gradient driven modes in an inhomogeneous tokamak plasma
      are identified. These modes represent temperature gradient (ion and electron)
      driven modes destabilized in the short wavelength regions with k( perpendicular
      )rho(i,e)>>1, respectively. The instability occurs due to a specific plasma
      response that significantly deviates from Boltzmann distribution in the regions
      k( perpendicular )rho(i,e)>>1.

PMID- 12225093
TI  - Dynamic critical behavior near the superfluid transition in 3He-4He mixtures in
      two loop order.
AB  - We calculated in two loop order the field theoretic renormalization group
      functions taking into account the decomposition of the dynamical vertex functions
      into the static vertex functions and genuine dynamical parts. The observation of
      this nonperturbative structure simplifies the theoretical expressions obtained by
      perturbation theory considerably and makes tractable a complete two loop
      calculation of the critical dynamics near the superfluid transition of 3He-4He
      mixtures (model F'). As a result, we obtain various transport coefficients, which
      govern the nonasymptotic and nonuniversal temperature dependence. We also correct
      long-standing results for the critical dynamics of the superfluid transition in
      pure 4He (model F) and for the dynamics of structural or magnetic phase
      transitions (model C).

PMID- 12225094
TI  - What do we learn from the local geometry of glass-forming liquids?
AB  - We examine the local geometry of a simulated glass-forming polymer melt. Using
      the Voronoi construction, we find that the distributions of Voronoi volume
      P(v(V)) and asphericity P(a) appear to be universal properties of dense liquids,
      supporting the use of packing approaches to understand liquid properties. We also
      calculate the average free volume <v(f)> along a path of constant density and
      find that <v(f)> extrapolates to zero at the same temperature T0 that the
      extrapolated relaxation time diverges. We relate <v(f)> to the Debye-Waller
      factor, which is measurable by neutron scattering.

PMID- 12225095
TI  - Pressure evolution of the high-frequency sound velocity in liquid water.
AB  - The high-frequency sound velocity v( infinity ) of liquid water has been
      determined to densities of 1.37 g/cm(3) by inelastic x-ray scattering. In
      comparison to the hydrodynamic sound velocity v(0), the increase of v( infinity )
      with density is substantially less pronounced, indicating that, at high density,
      the hydrogen-bond network is decreasingly relevant to the physical properties of
      liquid water. Furthermore, we observe an anomaly in v( infinity ) at densities
      around 1.12 g/cm(3), contrasting the smooth density evolution of v(0).

PMID- 12225096
TI  - Imaging delocalized electron clouds: photoionization of C(60) in Fourier
      reciprocal space.
AB  - The dynamics of the photoionization of the two outermost orbitals of C(60) has
      been studied in the oscillatory regime from threshold to the carbon K edge. We
      show that geometrical properties of the fullerene electronic hull, such as its
      diameter and thickness, are contained in the partial photoionization cross
      sections by examining ratios of partial cross sections as a function of the
      photon wave number in the Fourier conjugated space. Evaluated in this
      unconventional manner photoemission data reveal directly the desired spatial
      information.

PMID- 12225097
TI  - Ultrafast vibrational dynamics and stability of deuterated amorphous silicon.
AB  - Infrared four-wave mixing experiments performed upon deuterated amorphous silicon
      layers (a-Si:D) reveal profound differences in the dynamics of Si-D stretch
      vibrations compared to those of analogous Si-H vibrational modes in hydrogenated
      amorphous silicon (a-Si:H). Remarkably, transient-grating measurements of the
      population decay rate of the Si-D vibrations show single-exponential decay
      directly into collective modes of the a-Si host, bypassing the local bending
      modes of the defect into which the Si-H vibrations decay. Photon-echo
      measurements of the vibrational dephasing suggest at low temperature
      contributions from TO nonequilibrium phonons and at elevated temperatures elastic
      phonon scattering of TA phonons.

PMID- 12225098
TI  - Observation of an anomalous discontinuous liquid-structure change with
      temperature.
AB  - The nature of liquid structures with their changing behaviors remains an unsolved
      fundamental problem in many fields of science and technology. It has been widely
      accepted that liquid structures change gradually with temperature and/or
      pressure. With x-ray diffraction in the melt In-Sn80, however, we have confirmed
      that a temperature-dependent discontinuous structural change could occur in some
      binary liquids, which does not fall into any other up-to-date recognized liquid
      liquid changes. This finding, together with the recently recognized pressure
      induced liquid change, suggests that the conventional view on liquids should be
      revised.

PMID- 12225099
TI  - Density-fluctuation-induced swelling of polymer thin films in carbon dioxide.
AB  - We report an anomalous swelling of polymer thin films in carbon dioxide (CO(2))
      which is associated (in both locus and form) with the density fluctuation ridge
      that forms along the extension of the coexistence curve of gas and liquid in the
      P-T phase diagram. Neutron reflectivity results showed that CO(2) could be sorbed
      to a large extent ( approximately 60%) in thin polymer films even when the bulk
      miscibility of the polymer with CO(2) is very poor. The anomalous swelling is
      found to scale with the polymer radius of gyration (R(g)) and extends to a
      distance approximately 10 R(g).

PMID- 12225100
TI  - Homogeneity of a supersaturated solid solution.
AB  - Extended x-ray absorption fine structures, small-angle x-ray scattering, and
      atomistic model calculations have been employed to probe the homogeneity of the
      fcc solution created in Ag-Cu, a classical system demonstrating the extension of
      solubility across the entire miscibility gap through rapid quenching. Our results
      reveal that in many cases the supersaturated solutions formed have decomposition
      features on the scale of 1 nm. Conventional diffraction methods are inadequate in
      determining the level of supersaturation or the uniformity of such solid solution
      alloys.

PMID- 12225101
TI  - Re-entrant glass transition in a colloid-polymer mixture with depletion
      attractions.
AB  - Performing light scattering experiments we show that introducing short-ranged
      attraction to a colloid suspension of nearly hard spheres by addition of a free
      polymer produces new glass-transition phenomena. We observe a dramatic
      acceleration of the density fluctuations amounting to the melting of a colloidal
      glass. Upon increasing the strength of the attractions the system freezes into
      another nonergodic state sharing some qualitative features with gel states
      occurring at lower colloid packing fractions. This re-entrant glass transition is
      in qualitative agreement with recent theoretical predictions.

PMID- 12225102
TI  - Functional renormalization group at large N for disordered systems.
AB  - We introduce a method, based on an exact calculation of the effective action at
      large N, to bridge the gap between mean-field theory and renormalization in
      complex systems. We apply it to a d-dimensional manifold in a random potential
      for large embedding space dimension N. This yields a functional renormalization
      group equation valid for any d, which contains both the O(epsilon=4-d) results of
      Balents-Fisher and some of the nontrivial results of the Mezard-Parisi solution,
      thus shedding light on both. Corrections are computed at order O(1/N).
      Applications to the Kardar-Parisi-Zhang growth model, random field, and mode
      coupling in glasses are mentioned.

PMID- 12225103
TI  - Photo- and thermodesorption of helium on Pt(111).
AB  - In a detailed study of thermal desorption of monolayers of both 4He and 3He
      adsorbed on Pt(111) (binding energy about 9 meV), we have observed
      photodesorption induced by the blackbody radiation from a room temperature
      environment. This process proceeds independently of the thermal desorption.
      Theoretical treatments of both thermal and photodesorption are given and agree
      very well with the data in all important aspects. We conclude that the
      photodesorption is due to direct coupling of photons to the adsorbate.

PMID- 12225104
TI  - Mesoscopic relaxation in homoepitaxial metal growth.
AB  - We demonstrate that a size-dependent mesoscopic mismatch exists in homoepitaxy,
      which has a strong impact on the morphology of the islands and the substrate.
      Atomic scale calculations for double layer Cu islands on Cu(111) reveal that
      mesoscopic strain relaxations in both islands and the substrate strongly
      influence the shape of islands and can effect the details of atomic motion near
      the island.

PMID- 12225105
TI  - Reversible stress relaxation during precoalescence interruptions of volmer-weber
      thin film growth.
AB  - From in situ stress measurements, we have observed that a large component of the
      precoalescence compressive stress that develops during Volmer-Weber growth of
      polycrystalline Cu films relaxes reversibly. This phenomenon is similar to the
      reversible stress relaxation previously observed in the postcoalescence regime.
      We have also observed that less than a tenth of a monolayer of deposition leads
      to an instantaneous stress of order 1 GPa. The stress changes in both the
      precoalescence and postcoalescence regimes of growth are explained by changes in
      the adatom population during and after deposition.

PMID- 12225106
TI  - Single-molecule reaction and characterization by vibrational excitation.
AB  - Controlled chemical reaction of single trans-2-butene molecules on the Pd(110)
      surface was realized by dosing tunneling electrons from the tip of a scanning
      tunneling microscope at 4.7 K. The reaction product was identified as a 1,3
      butadiene molecule by inelastic electron tunneling spectroscopy. Threshold
      voltage for the reaction is approximately 365 mV, which coincides with the
      vibrational excitation of the C-H stretching mode. The reaction was ascertained
      to be caused by C-H bond dissociation by multiple vibrational excitations of the
      C-H stretching mode via inelastic electron tunneling process.

PMID- 12225107
TI  - Band-gap problem in semiconductors revisited: effects of core states and many
      body self-consistency.
AB  - A novel picture of the quasiparticle (QP) gap in prototype semiconductors Si and
      Ge emerges from an analysis based on all-electron, self-consistent, GW
      calculations. The deep-core electrons are shown to play a key role via the
      exchange diagram-if this effect is neglected, Si becomes a semimetal. Contrary to
      current lore, the Ge 3d semicore states (e.g., their polarization) have no impact
      on the GW gap. Self-consistency improves the calculated gaps-a first clear-cut
      success story for the Baym-Kadanoff method in the study of real-materials
      spectroscopy; it also has a significant impact on the QP lifetimes. Our results
      embody a new paradigm for ab initio QP theory.

PMID- 12225108
TI  - Self-consistent green function approach for calculation of electronic structure
      in transition metals.
AB  - We present an approach for self-consistent calculations of the many-body Green
      function in transition metals. The distinguishing feature of our approach is the
      use of one-site approximation and the self-consistent quasiparticle wave function
      basis set obtained from the solution of the Schrodinger equation with a nonlocal
      potential. We analyze several sets of skeleton diagrams as generating functionals
      for the Green function self-energy, including GW and fluctuating exchange sets.
      Calculations for Fe and Ni revealed stronger energy dependence of the effective
      interaction and self-energy of the d electrons near the Fermi level compared to s
      and p electron states.

PMID- 12225109
TI  - Calogero-Moser models with noncommutative spin interactions.
AB  - We construct integrable generalizations of the elliptic Calogero-Sutherland-Moser
      model of particles with spin, involving noncommutative spin interactions. The
      spin coupling potential is a modular function and, generically, breaks the global
      spin symmetry of the model down to a product of U(1) phase symmetries. Previously
      known models are recovered as special cases.

PMID- 12225110
TI  - Absolute and approximate calculations of electron-energy-loss spectroscopy edge
      thresholds.
AB  - Systematic studies of binding energies for the electron excitation of core levels
      for atoms, molecules, and solids have been calculated with various density
      functional theories. The generalized gradient approximation provides the most
      accurate description of the absolute binding energies when spin polarization is
      included. Relative core level shifts can be determined to within 0.5 eV without
      spin polarization. Core level shifts can be predicted from ground-state
      eigenvalue differences only when comparing environments of similar
      electronegativity. Such is the case for the O K edge, but not the Si L edge at
      Si/SiO(2) interfaces in nanotransistors.

PMID- 12225111
TI  - Crossover between universality classes in the statistics of rare events in
      disordered conductors.
AB  - The crossover from orthogonal to the unitary universality classes in the
      distribution of the anomalously localized states (ALS) in two-dimensional
      disordered conductors is traced as a function of magnetic field. We demonstrate
      that the microscopic origin of the crossover is the change in the symmetry of the
      underlying disorder configurations that are responsible for ALS. These disorder
      configurations are of weak magnitude (compared to the Fermi energy) and of small
      size (compared to the mean free path). We find their shape explicitly by means of
      the direct optimal fluctuation method.

PMID- 12225112
TI  - Field-modulated carrier transport in carbon nanotube transistors.
AB  - We have investigated the electrical transport properties of carbon nanotube field
      effect transistors as a function of channel length, gate dielectric film
      thickness, and dielectric material. Our experiments show that the bulk properties
      of the semiconducting carbon nanotubes do not limit the current flow through the
      metal/nanotube/metal system. Instead, our results can be understood in the
      framework of gate and source-drain field induced modulation of the nanotube band
      structure at the source contact. The existence of one-dimensional Schottky
      barriers at the metal/nanotube interface determines the device performance and
      results in an unexpected scaling behavior.

PMID- 12225113
TI  - Slow oscillations of magnetoresistance in quasi-two-dimensional metals.
AB  - Slow oscillations of the interlayer magnetoresistance observed in the layered
      organic metal beta-(BEDT-TTF)(2)IBr(2) are shown to originate from the slight
      warping of its Fermi surface rather than from independent small cyclotron orbits.
      Unlike the usual Shubnikov-de Haas effect, these oscillations are not affected by
      the temperature smearing of the Fermi distribution and can therefore become
      dominant at high enough temperatures. We suggest that the slow oscillations are a
      general feature of clean quasi-two-dimensional metals and discuss possible
      applications of the phenomenon.

PMID- 12225114
TI  - Disproportionation phenomena on free and strained Sn/Ge(111) and Sn/Si(111)
      surfaces.
AB  - Distortions of the sqrt[3]x sqrt[3] Sn/Ge(111) and Sn/Si(111) surfaces are shown
      to reflect a disproportionation of an integer pseudocharge, Q, related to the
      surface band occupancy. A novel understanding of the (3 x 3)-1U ("1 up, 2 down")
      and 2U ("2 up, 1 down") distortions of Sn/Ge(111) is obtained by a theoretical
      study of the phase diagram under strain. Positive strain keeps the unstrained
      value Q=3 but removes distortions. Negative strain attracts pseudocharge from the
      valence band causing first a (3 x 3)-2U distortion (Q=4) on both Sn/Ge and Sn/Si,
      and eventually a (sqrt[3] x sqrt[3])-3U ("all up") state with Q=6. The
      possibility of a fluctuating phase in unstrained Sn/Si(111) is discussed.

PMID- 12225115
TI  - Interactions and disorder in quantum dots: instabilities and phase transitions.
AB  - Using a fermionic renormalization group approach, we analyze a model where the
      electrons diffusing on a quantum dot interact via Fermi-liquid interactions.
      Describing the single-particle states by random matrix theory, we find that
      interactions can induce phase transitions (or crossovers for finite systems) to
      regimes where fluctuations and collective effects dominate at low energies.
      Implications for experiments and numerical work on quantum dots are discussed.

PMID- 12225116
TI  - Effect of spin-orbit scattering on the magnetic and superconducting properties of
      nearly ferromagnetic metals: application to granular Pt.
AB  - We calculate the effect of scattering on the static, exchange enhanced, spin
      susceptibility and show that, in particular, spin-orbit scattering leads to a
      reduction of the giant moments and spin glass freezing temperature due to dilute
      magnetic impurities. The harmful spin fluctuation contribution to the intragrain
      pairing interaction is strongly reduced opening the way for BCS
      superconductivity. We are thus able to explain the superconducting and magnetic
      properties recently observed in granular Pt as being due to scattering effects in
      single small grains.

PMID- 12225117
TI  - Origin of the enhanced copper spin echo decay rate in the pseudogap regime of the
      multilayer high-T(c) cuprates.
AB  - We report measurements of the anisotropy of the spin echo decay for the inner
      layer Cu site of the triple layer cuprate Hg(0.8)Re(0.2)Ba(2)Ca(2)Cu(3)O(8)
      (T(c)=126 K). The angular dependence of the second moment (T(-2)(2M) identical
      with <Deltaomega(2)>) deduced from the decay curves indicates that T(-2)(2M) for
      H0 parallel c is enhanced in the pseudogap regime below T(pg) approximately 170
      K, as seen in bilayer systems. Comparison of T(-2)(2M) between H0 parallel c and
      H0 perpendicular c indicates that this enhancement is caused by electron spin
      correlations between the inner and the outer CuO2 layers. The results provide the
      answer to the long-standing controversy regarding the opposite T dependences of
      (T1T)(-1) and T(-2)(2G) (T(2G): Gaussian component) in the pseudogap regime of
      multilayer systems.

PMID- 12225118
TI  - Magnetic field effect on the pseudogap temperature within precursor
      superconductivity.
AB  - We determine the magnetic-field dependence of the pseudogap closing temperature
      T* within a precursor superconductivity scenario. Detailed calculations with an
      anisotropic lattice model with d-wave superconductivity account for a recently
      determined experimental relation in BSCCO between the pseudogap closing field and
      the pseudogap temperature at zero field, as well as for the weak initial
      dependence of T* at low fields. Our results indicate that the available
      experimental data are fully compatible with a superconducting origin of the
      pseudogap in cuprate superconductors.

PMID- 12225119
TI  - Monitoring statistical magnetic fluctuations on the nanometer scale.
AB  - Statistical fluctuations of the magnetization are measured on the nanometer
      scale. As the experimental monitor we use the characteristic photoluminescence
      signal of a single electron-hole pair confined in one magnetic semiconductor
      quantum dot, which sensitively depends on the alignment of the magnetic ion
      spins. Quantitative access to statistical magnetic fluctuations is obtained by
      analyzing the linewidth broadening of the single dot emission. Our all-optical
      technique allows us to address a magnetic moment of only approximately equal 100
      micro(B) and to resolve statistical changes on the order of a few micro(B).

PMID- 12225120
TI  - Disorder induced quantum phase transition in random-exchange spin-1/2 chains.
AB  - We investigate the effect of quenched bond disorder on the anisotropic
      antiferromagnetic spin-1/2 (XXZ) chain as a model for disorder-induced quantum
      phase transitions. We find nonuniversal behavior of the average correlation
      functions for weak disorder, followed by a quantum phase transition into a
      strongly disordered phase with only short-range xy correlations. We find no
      evidence for the universal strong-disorder fixed point predicted by the real
      space renormalization group, suggesting a qualitatively different view of the
      relationship between quantum fluctuations and disorder.

PMID- 12225121
TI  - Spin flop transition in a finite antiferromagnetic superlattice: evolution of the
      magnetic structure.
AB  - An antiferromagnetic (AF) superlattice of Fe/Cr(211) is used as a model system to
      study magnetic transitions in a finite-size geometry. With polarization neutron
      reflectometry the magnetic structure at the surface spin-flop transition and its
      evolution with field is determined. A domain wall created near the surface
      penetrates the superlattice with increasing field, splitting it into two
      antiphase, AF domains. After reaching the center the spin-flopped phase spreads
      throughout the superlattice. The experimental results are in substantial
      agreement with theoretical and numerical predictions.

PMID- 12225122
TI  - Role of the carrier-envelope offset phase of few-cycle pulses in nonperturbative
      resonant nonlinear optics.
AB  - We study the influence of the carrier-envelope offset phase of few-cycle pulses
      on nonperturbative resonant extreme nonlinear optics in a semiconductor. If the
      Rabi frequency becomes comparable to the light frequency, the different Rabi
      sidebands interfere around twice the laser center frequency, giving rise to a
      signal which strongly depends on the carrier-envelope offset phase. This
      signature should be measurable in GaAs samples.

PMID- 12225123
TI  - Polarization-based adjustable memory behavior in relaxor ferroelectrics.
AB  - The irreversible decay of the spontaneous polarization above the phase-transition
      temperature is a limiting factor in any application of ferroelectric crystals.
      Here we show that electric fields applied at high temperatures induce a preferred
      direction in the crystal which is stable even after repeated heating and cooling
      through the phase transition. This preference in direction leads to a
      reorientation of domains in the ferroelectric phase. We use pyroelectric
      measurements to show that the directional preference originates from internal
      charge carriers interacting with domain walls.

PMID- 12225124
TI  - Efficient universal leakage elimination for physical and encoded qubits.
AB  - Decoherence-induced leakage errors can couple a physical or encoded qubit to
      other levels, thus potentially damaging the qubit. They can therefore be very
      detrimental in quantum information processing and require special attention. Here
      we present a general method for removing such errors by using simple decoupling
      and recoupling pulse sequences. The proposed gates are experimentally accessible
      in a variety of promising quantum-computing proposals.

PMID- 12225125
TI  - Method for direct detection of quantum entanglement.
AB  - Basing on positive maps separability criterion we propose the experimentally
      viable, direct detection of quantum entanglement. It is efficient and does not
      require any a priori knowledge about the state. For two qubits it provides a
      sharp (i.e., "if and only if") separability test and estimation of amount of
      entanglement. We view this method as a new form of quantum computation, namely,
      as a decision problem with quantum data structure.

PMID- 12225126
TI  - Kinetically locked-in colloidal transport in an array of optical tweezers.
AB  - We describe measurements of colloidal transport through arrays of micrometer
      scale potential wells created with holographic optical tweezers. Varying the
      orientation of the trap array relative to the external driving force results in a
      hierarchy of lock-in transitions analogous to symmetry-selecting processes in a
      wide variety of systems. Focusing on colloid as a model system provides the first
      opportunity to observe the microscopic mechanisms of kinetic lock-in transitions
      and reveals a new class of statistically locked-in states. This particular
      realization also has immediate applications for continuously fractionating
      particles, biological cells, and macromolecules.

PMID- 12225127
TI  - Influence of polymer-excluded volume on the phase-behavior of colloid-polymer
      mixtures.
AB  - We determine the depletion-induced phase-behavior of hard-sphere colloids and
      interacting polymers by large-scale Monte Carlo simulations using very accurate
      coarse-graining techniques. A comparison with standard Asakura-Oosawa model
      theories and simulations shows that including excluded-volume interactions
      between polymers leads to qualitative differences in the phase diagrams. These
      effects become increasingly important for larger relative polymer size. Our
      simulation results agree quantitatively with recent experiments.

PMID- 12225128
TI  - Stochastic resonance mechanism in aerosol index dynamics.
AB  - We consider satellite time series concerning the atmospheric aerosol content. We
      prove that these time series are well described by a stochastic dynamical model.
      The principal peak in the power spectrum of these signals can be explained by
      stochastic resonance, linking variable external factors, such as Sun-Earth
      radiation budget and local insolation, to fluctuations on smaller spatial and
      temporal scale due to internal weather and antrophic components.

PMID- 12225129
TI  - Comment on "weak anisotropy and disorder dependence of the in-plane
      magnetoresistance in high-mobility (100) si-inversion layers".

PMID- 12225131
TI  - Reflectance measurements and superconductivity in MgB2.

PMID- 12225133
TI  - Dynamics of dark solitons in elongated Bose-Einstein condensates.
AB  - We find two types of moving dark soliton textures in elongated condensates:
      nonstationary kinks and proper dark solitons. The latter have a flat notch region
      and we obtain the diagram of their dynamical stability. At finite temperatures
      the dynamically stable solitons decay due to the thermodynamic instability. We
      develop a theory of their dissipative dynamics and explain experimental data.

PMID- 12225134
TI  - Crossover from one to three dimensions for a gas of hard-core bosons.
AB  - We develop a variational theory of the crossover from the one-dimensional (1D)
      regime to the 3D regime for ultracold Bose gases in thin waveguides. Within the
      1D regime we map out the parameter space for fermionization, which may span the
      full 1D regime for suitable transverse confinement.

PMID- 12225135
TI  - Out-of-equilibrium states as statistical equilibria of an effective dynamics in a
      system with long-range interactions.
AB  - We study the formation of coherent structures in a system with long-range
      interactions where particles moving on a circle interact through a repulsive
      cosine potential. Nonequilibrium structures are shown to correspond to
      statistical equilibria of an effective dynamics, which is derived using averaging
      techniques. This simple behavior might be a prototype of others observed in more
      complicated systems with long-range interactions, such as two-dimensional
      incompressible fluids and wave-particle interaction in a plasma.

PMID- 12225137
TI  - Relativistic hydrodynamic scaling from the dynamics of quantum field theory.
AB  - Relativistic hydrodynamic scaling or boost invariance is a particularly important
      hydrodynamic regime, describing collective flows of relativistic many body
      systems and is used in the interpretation of experiments from high-energy cosmic
      rays to relativistic heavy-ion collisions. We show evidence for the emergence of
      hydrodynamic scaling from the dynamics of relativistic quantum field theory. We
      consider a scalar lambdaphi(4) model in 1+1 dimensions in the Hartree
      approximation and study the relativistic collisions of two kinks and the decay of
      a localized high-energy density region. We find that thermodynamic scalar
      isosurfaces show approximate boost invariance at high-energy densities.

PMID- 12225138
TI  - Slow-down collisions and nonsequential double ionization in classical
      simulations.
AB  - We use classical simulations to analyze the dynamics of nonsequential double
      electron short-pulse photoionization. We utilize a microcanonical ensemble of
      10(5) two-electron "trajectories," a number large enough to provide large
      subensembles and even sub-subensembles associated with double ionization. We
      focus on key events in the final doubly ionized subensemble and back-analyze the
      subensemble's history, revealing a classical slow-down scenario for nonsequential
      double ionization. We analyze the dynamics of these slow-down collisions and find
      that a good phase match between the motions of the electrons can lead to very
      effective energy transfer, followed by escape over a suppressed barrier.

PMID- 12225139
TI  - Direct and indirect pathways in strong field atomic ionization dynamics.
AB  - With the help of a suitably chosen momentum-space analysis, we study some of the
      basic mechanisms governing the physics of the processes occurring when atoms are
      submitted to intense infrared laser pulses, with peak intensities 10(14) W cm(
      2)</=I(max)</=10(15) W cm(-2). This intensity range is especially interesting
      because two highly nonlinear atomic processes, namely, above threshold ionization
      and high-order harmonic generation, take place with significant probabilities.
      Several issues regarding the dynamics of these processes are resolved, with
      special attention devoted to the mechanism leading to the ejection of the
      photoelectrons in this intensity range.

PMID- 12225136
TI  - First observation of the doubly charmed baryon Xi(+)(cc).
AB  - We observe a signal for the doubly charmed baryon Xi(+)(cc) in the charged decay
      mode Xi(+)(cc)-->Lambda(+)(c)K-pi(+) in data from SELEX, the charm
      hadroproduction experiment at Fermilab. We observe an excess of 15.9 events over
      an expected background of 6.1+/-0.5 events, a statistical significance of
      6.3sigma. The observed mass of this state is 3519+/-1 MeV/c(2). The Gaussian mass
      width of this state is 3 MeV/c(2), consistent with resolution; its lifetime is
      less than 33 fs at 90% confidence.

PMID- 12225140
TI  - "Two-Photon" coincidence imaging with a classical source.
AB  - Coincidence imaging is a technique that extracts an image of a test system from
      the statistics of photons transmitted by a reference system when the two systems
      are illuminated by a source possessing appropriate correlations. It has recently
      been argued that quantum entangled sources are necessary for the implementation
      of this technique. We show that this technique does not require entanglement, and
      we provide an experimental demonstration of coincidence imaging using a classical
      source. We further find that any kind of coincidence imaging technique which uses
      a "bucket" detector in the test arm is incapable of imaging phase-only objects,
      whether a classical or quantum source is employed.

PMID- 12225141
TI  - New relativistic effects in the dynamics of nonlinear hydrodynamical waves.
AB  - In Newtonian and relativistic hydrodynamics the Riemann problem determines the
      evolution of a fluid which is initially characterized by two states having
      different rest-mass density, pressure, and velocity. When the fluid is allowed to
      relax, one of three possible wave patterns is produced, corresponding to the
      propagation in opposite directions of two nonlinear hydrodynamical waves. New
      effects emerge in a relativistic Riemann problem when velocities tangential to
      the initial discontinuity are present. A smooth transition from one wave pattern
      to another can be produced by varying the initial tangential velocities while
      maintaining the initial states unmodified. These special relativistic effects are
      produced by the Lorentz factors and do not have a Newtonian counterpart.

PMID- 12225142
TI  - Ablation effects on weakly nonlinear Rayleigh-Taylor instability with a finite
      bandwidth.
AB  - A weakly nonlinear but numerically tractable model (to third order in amplitude
      and including bandwidth effects) has been developed for the ablative Rayleigh
      Taylor (RT) instability. Model results clearly show growth reduction from linear
      ablative RT values and even amplitude saturation in some realistic cases. For
      excitation of a band of wave numbers near the cutoff for growth, the behavior is
      dominated by the mode with the largest linear growth rate, and not by the mode
      with the largest initial amplitude. This type of model is likely to be important
      for the future assessment of the RT effects on specific target designs of the
      inertial confinement fusion.

PMID- 12225143
TI  - Interaction between small-scale zonal flows and large-scale turbulence: a theory
      for ion transport intermittency in Tokamak plasmas.
AB  - Interaction between small-scale zonal flows and large-scale turbulence is
      investigated. The key mechanism is identified as radially nonlocal mode coupling.
      Fluctuating energy can be nonlocally transferred from the unstable longer to the
      stable or damped shorter wavelength region, so that the turbulence spectrum is
      seriously deformed and deviates from the nonlinear power law structure. Three
      dimensional gyrofluid ion-temperature gradient (ITG) turbulence simulations show
      that an ion transport bursting behavior is consistently linked to the spectral
      deformity with the causal role of ITG-generated zonal flows in tokamak plasmas.

PMID- 12225144
TI  - Transparency of magnetized plasma at the cyclotron frequency.
AB  - Electromagnetic radiation is strongly absorbed by a magnetized plasma if the
      radiation frequency equals the cyclotron frequency of plasma electrons. It is
      demonstrated that absorption can be completely canceled in the presence of a
      magnetostatic field of an undulator, or a second radiation beam, resulting in
      plasma transparency at the cyclotron frequency. This effect is reminiscent of the
      electromagnetically induced transparency (EIT) of three-level atomic systems,
      except that it occurs in a completely classical plasma. Unlike the atomic
      systems, where all the excited levels required for EIT exist in each atom, this
      classical EIT requires the excitation of nonlocal plasma oscillation. A
      Lagrangian description was used to elucidate the physics of the plasma
      transparency and control of group and phase velocity. This control leads to
      applications for electromagnetic pulse compression and electron/ion acceleration.

PMID- 12225145
TI  - Controlling the profile of ion-cyclotron-resonant ions in JET with the wave
      induced pinch effect.
AB  - Experiments on the JET tokamak show that the wave-induced pinch in the presence
      of toroidally asymmetric waves can provide a tool for controlling the profile of
      ion-cyclotron-resonant 3He ions. Direct evidence for the wave-induced pinch has
      been obtained from the measured gamma-ray emission profiles. Concurrent
      differences in the excitation of Alfven eigenmodes (AEs), sawtooth stabilization,
      electron temperatures, and fast-ion stored energies are observed. The measured
      location of the AEs and gamma-ray emission profiles are consistent with the fast
      ion radial gradient providing the drive for AEs.

PMID- 12225146
TI  - Heat capacity of 3He in aerogel.
AB  - The heat capacity of pure 3He in low density aerogel is measured at 22.5 bars.
      The superfluid response is simultaneously monitored with a torsional oscillator.
      A slightly rounded heat capacity peak, 65 microK in width, is observed at the 3He
      aerogel superfluid transition, T(ca). Subtracting the bulk 3He contribution, the
      heat capacity shows a Fermi-liquid form above T(ca). We can fit the heat capacity
      attributed to superfluid within the aerogel with a rounded BCS form accounting
      for 0.30 of the nonbulk fluid in the aerogel, or by assuming a substantial
      reduction in the superfluid order parameter. Both approaches are consistent with
      earlier superfluid density measurements.

PMID- 12225147
TI  - Nodal effects in dislocation mobility.
AB  - We show that, contrary to the prevailing perception, dislocations can become more
      mobile by zipping together to form junctions. In a series of direct atomistic
      simulations, the critical stress to move a junction network in a [110] plane of
      bcc molybdenum is found to be always smaller ( approximately 50%) than that
      required to move isolated dislocations. Our data support a previously proposed
      hypothesis about the nature of anomalous slip in bcc transition metals, yet offer
      a different atomistic mechanism for conservative motion of screw dislocation
      networks. The same data suggest a hierarchy of motion mechanisms in which lower
      dimensional crystal imperfections control the rate of sliding along the low-angle
      twist boundaries.

PMID- 12225148
TI  - Planar defects and incommensurate phases in highly ordered perovskite solid
      solutions.
AB  - A first-principles-derived approach is used to study the effects of planar
      defects on structural properties of a rocksalt-ordered Pb(Sc0.5Nb0.5)O3 alloy.
      These defects lead to unusual features, including a less symmetrical ground state
      with respect to the perfectly ordered material. We also propose that a simple and
      original mechanism, involving these defects, may be responsible for the existence
      and anomalous characteristics of the incommensurate phases observed in insulating
      perovskites.

PMID- 12225149
TI  - First-principles study of the temperature-pressure phase diagram of BaTiO3.
AB  - We investigate the temperature-pressure phase diagram of BaTiO3 using a first
      principles effective-Hamiltonian approach. We find that the zero-point motion of
      the ions affects the form of the phase diagram dramatically. Specifically, when
      the zero-point fluctuations are included in the calculations, all the polar
      (tetragonal, orthorhombic, and rhombohedral) phases of BaTiO3 survive down to 0
      K, while only the rhombohedral phase does otherwise. This behavior results from a
      practical equivalence between thermal and quantum fluctuations. Our work confirms
      the essential correctness of the phase diagram proposed by Ishidate et al. [Phys.
      Rev. Lett. 78, 2397 (1997)]].

PMID- 12225150
TI  - Spontaneous decay of excited atomic states near a carbon nanotube.
AB  - The spontaneous decay process of an excited atom placed inside or outside a
      carbon nanotube is analyzed. Calculations have been performed for various achiral
      nanotubes. The effect of the nanotube surface is shown to increase the atomic
      spontaneous decay rate by up to 6 orders of magnitude compared with that of the
      same atom in vacuum. This increase is associated with nonradiative decay via
      surface excitations in the nanotube.

PMID- 12225151
TI  - Hydrogen-bond dynamics near a micellar surface: origin of the universal slow
      relaxation at complex aqueous interfaces.
AB  - The dynamics of hydrogen bonds among water molecules themselves and with the
      polar head groups (PHG) at a micellar surface have been investigated by long
      molecular dynamics simulations. The lifetime of the hydrogen bond between a PHG
      and a water molecule is found to be much longer than that between any two water
      molecules, and is likely to be a general feature of hydrophilic surfaces of
      organized assemblies. Analyses of individual water trajectories suggest that
      water molecules can remain bound to the micellar surface for more than 100 ps.
      The activation energy for such a transition from the bound to a free state for
      the water molecules is estimated to be about 3.5 kcal/mol.

PMID- 12225152
TI  - Observation of acoustical memory in LiNbO3.
AB  - A new physical effect is reported. In single crystals of lithium niobate
      (LiNbO3), we have observed an acoustical memory effect. An acoustical tone burst
      is stored inside the crystal and reemitted at a later time. This memory signal is
      related to the acousto-electrical properties of the ferroelectric medium.
      Futhermore, it is shown to be sensitive to both temperature and frequency.

PMID- 12225153
TI  - Exact solution of a drop-push model for percolation.
AB  - Motivated by a computer science algorithm known as "linear probing with hashing,"
      we study a new type of percolation model whose basic features include a
      sequential "dropping" of particles on a substrate followed by their transport via
      a "pushing" mechanism. Our exact solution in one dimension shows that, unlike the
      ordinary random percolation model, the drop-push model has nontrivial spatial
      correlations generated by the dynamics itself. The critical exponents in the drop
      push model are also different from those of the ordinary percolation. The
      relevance of our results to computer science is pointed out.

PMID- 12225154
TI  - Existence and nature of a freezing transition inside three-dimensional arrays of
      narrow channels.
AB  - The density functional for matter confined inside a three-dimensional array of
      narrow channels is constructed. It is shown that the effect of long range
      interactions amounts to a three-dimensional quadratic perturbation on an array of
      one-dimensional hard rods. Hence, it follows that the recently proposed freezing
      transition of atoms confined in nanotube arrays is continuous. This conclusion is
      validated beyond mean field theory by Monte Carlo simulations in the NPT
      ensemble.

PMID- 12225155
TI  - Role of long range interaction in oxygen superstructure formation on Cu(001) and
      Ni(001).
AB  - On the basis of electronic structure calculations, we show that the long range
      Coulomb interaction provides the driving mechanism for oxygen overlayer formation
      on Cu(001). We illustrate that this interaction in the precursor c(2 x 2) phase
      induces a missing row reconstruction of Cu(001), and leads to the (2sqrt[2] x
      sqrt[2])R45 degrees O structure, which has strong covalent pO-dCu coupling. For
      the c(2 x 2)O overlayer on Ni(001) and Cu(001), we show that pO-dNi bonding is
      larger than pO-dCu and serves to neutralize the perturbation of the Coulomb
      interaction induced by the O overlayer. Consequently, c(2 x 2)O/Ni(001)) is
      stable while c(2 x 2)O/Cu(001) exists only in limited environments.

PMID- 12225156
TI  - Arsenic flux dependence of island nucleation on InAs(001).
AB  - The initial stages of InAs(001) homoepitaxial growth are investigated using a
      combination of kinetic Monte Carlo simulations based on ab initio density
      functional theory and scanning tunneling microscopy. In the two dimensional
      island nucleation mode investigated, the island number density is found to
      decrease with increasing As. This behavior is explained by a suppression of the
      effective In-adatom density leading to a reduction in island nucleation. The
      relevant microscopic processes responsible for this reduction are identified.

PMID- 12225157
TI  - Resonating-valence-bond States and ferromagnetic correlations in the doped
      triangular Mott insulator.
AB  - The two-dimensional t-J model on a triangular lattice is studied using high
      temperature expansions. By studying the entropy and spin susceptibility, we find
      that the sign of the hopping integral t is very crucial. In the case of t>0, the
      peak of the spin susceptibility moves to the high-temperature region with hole
      doping, which indicates the appearance of the resonating-valence-bond state. In
      contrast, for t<0, the peak of the spin susceptibility disappears with hole
      doping and the entropy at low temperatures behaves as S=gammaT with large
      coefficient gamma, representing a large effective mass. This behavior is
      understood from the competition between Nagaoka's ferromagnetism and singlet
      formation.

PMID- 12225158
TI  - Berry-phase calculation of magnetic screening and rotational g factor in
      molecules and solids.
AB  - The orbital magnetic moment due to rotation or pseudorotation in a molecule or a
      solid and the corresponding rotational g factor are formulated using the Berry
      phase technique and standard density functional plane wave methods. Among the
      simplest molecules, H+2, H2, C2H2, CH4, and CF4, with known rotational g factors,
      are used as test cases with excellent results. Alternative, faster localized
      orbital calculations including the magnetic coupling through heuristic Peierls
      phase factors are also tested and found to be viable, though less accurate.
      Application to pseudorotations is exemplified in benzene. It is proposed that
      these methods will be suited for application to pseudorotations in solids.

PMID- 12225159
TI  - Semiclassical theory of spin-orbit interactions using spin coherent states.
AB  - We formulate a semiclassical theory for systems with spin-orbit interactions.
      Using spin coherent states, we start from the path integral in an extended phase
      space, formulate the classical dynamics of the coupled orbital and spin degrees
      of freedom, and calculate the ingredients of Gutzwiller's trace formula for the
      density of states. For a two-dimensional quantum dot with a spin-orbit
      interaction of Rashba type, we obtain satisfactory agreement with fully quantum
      mechanical calculations. The mode-conversion problem, which arose in an earlier
      semiclassical approach, has hereby been overcome.

PMID- 12225160
TI  - Reversible quantum brownian heat engines for electrons.
AB  - Brownian heat engines use local temperature gradients in asymmetric potentials to
      move particles against an external force. The energy efficiency of such machines
      is generally limited by irreversible heat flow carried by particles that make
      contact with different heat baths. Here we show that, by using a suitably chosen
      energy filter, electrons can be transferred reversibly between reservoirs that
      have different temperatures and electrochemical potentials. We apply this result
      to propose heat engines based on mesoscopic semiconductor ratchets, which can
      quasistatically operate arbitrarily close to Carnot efficiency.

PMID- 12225161
TI  - Phase diagram of interacting composite fermions in the bilayer nu=2/3 quantum
      hall effect.
AB  - We study the phase diagram of composite fermions (CFs) in the presence of spin
      and pseudospin degrees of freedom in the bilayer nu=2/3 quantum Hall (QH) state.
      Activation studies elucidate the existence of three different QH states with two
      different types of hysteresis in the magnetotransport. While a noninteracting CF
      model provides a qualitative account of the phase diagram, the observed
      renormalization of tunneling gap and a non-QH state at high densities are not
      explained in the noninteracting CF model, and are suggested to be manifestations
      of interactions between CFs.

PMID- 12225162
TI  - Non-fermi-liquid behavior in Sr2RuO4 with nonmagnetic impurities.
AB  - We report that the quasi-two-dimensional Fermi-liquid behavior of the spin
      triplet superconductor Sr2RuO4 breaks down in the vicinity of the critical
      impurity concentration for the onset of magnetic order induced by nonmagnetic
      Ti4+ impurities. The non-Fermi-liquid behavior is interpreted in terms of the two
      dimensional antiferromagnetic fluctuations, which arise mainly from the nesting
      within one of the Fermi-surface sheets. We argue against the main role of such
      magnetic fluctuations in the pairing mechanism.

PMID- 12225163
TI  - Integral equation generates high-temperature expansion of the Heisenberg chain.
AB  - Recently a new integral equation describing the thermodynamics of the 1D
      Heisenberg model was discovered by Takahashi. Using the integral equation we have
      succeeded in obtaining the high-temperature expansion of the specific heat and
      the magnetic susceptibility up to O[(J/T)(100)]. This is much higher than those
      obtained so far by the standard methods such as the linked-cluster algorithm. Our
      results will be useful to examine various approximation methods to extrapolate
      the high-temperature expansion to the low temperature region.

PMID- 12225164
TI  - Phase diagram of the random Heisenberg antiferromagnetic spin-1 chain.
AB  - We present a new perturbative real space renormalization group (RG) to study
      random quantum spin chains and other one-dimensional disordered quantum systems.
      The method overcomes problems of the original approach which fails for quantum
      random chains with spins larger than S=1/2. Since it works even for weak
      disorder, we are able to obtain the zero temperature phase diagram of the random
      antiferromagnetic Heisenberg spin-1 chain as a function of disorder. We find a
      random singlet phase for strong disorder. As the disorder decreases, the system
      shows a crossover from a Griffiths to a disordered Haldane phase.

PMID- 12225165
TI  - Mott domains of bosons confined on optical lattices.
AB  - In the absence of a confining potential, the boson-Hubbard model exhibits a
      superfluid to Mott insulator quantum phase transition at commensurate fillings
      and strong coupling. We use quantum Monte Carlo simulations to study the ground
      state of the one-dimensional bosonic Hubbard model in a trap. Some, but not all,
      aspects of the Mott insulating phase persist. Mott behavior occurs for a
      continuous range of incommensurate fillings, very different from the unconfined
      case, and the establishment of the Mott phase does not proceed via a traditional
      quantum phase transition. These results have important implications for
      interpreting experiments on ultracold atoms on optical lattices.

PMID- 12225166
TI  - Surface-enhanced emission from single semiconductor nanocrystals.
AB  - The fluorescence behavior of single CdSe(ZnS) core-shell nanocrystal (NC) quantum
      dots is dramatically affected by electromagnetic interactions with a rough metal
      film. Observed changes include a fivefold increase in the observed fluorescence
      intensity of single NCs, a striking reduction in their fluorescence blinking
      behavior, complete conversion of the emission polarization to linear, and single
      NC exciton lifetimes that are >10(3) times faster. The enhanced excited state
      decay process for NCs coupled to rough metal substrates effectively competes with
      the Auger relaxation process, allowing us to observe both charged and neutral
      exciton emission from these NC quantum dots.

PMID- 12225167
TI  - Time-resolved charge carrier generation from higher lying excited states in
      conjugated polymers.
AB  - Sub-ps three-pulse transient differential transmission spectroscopy using two
      excitation pulses is used to directly investigate the generation of charge
      carriers in ladder-type poly(para)phenyl in bulk film. The role of higher excited
      singlet states of both even and odd symmetry is examined and the dynamics of the
      major processes involved is described quantitatively. The charge generation
      efficiency is found to depend strongly on the delay between the two excitation
      pulses. This is explained by the interplay between internal conversion,
      excitation energy migration, and on-site vibronic relaxation.

PMID- 12225168
TI  - Dielectric constants of Zr silicates: a first-principles study.
AB  - Using density-functional theory, we compute the optical and static dielectric
      constants for a set of Zr silicates modeled by various SiO2 crystals, with Zr
      atoms substitutional to Si, and by an amorphous structure. We then derive a
      microscopic scheme that relates the dielectric constants to structural units
      centered on Si and Zr atoms through the definition of characteristic parameters.
      Applied to amorphous (ZrO2)(x)(SiO2)(1-x), these schemes describe the observed
      dependence of the dielectric constants on the Zr concentration and highlight the
      role of ZrO6 units.

PMID- 12225169
TI  - First-principles approach to insulators in finite electric fields.
AB  - We describe a method for computing the response of an insulator to a static,
      homogeneous electric field. It consists of iteratively minimizing an electric
      enthalpy functional expressed in terms of occupied Bloch-like states on a uniform
      grid of k points. The functional has equivalent local minima below a critical
      field E(c) that depends inversely on the density of k points; the disappearance
      of the minima at E(c) signals the onset of Zener breakdown. We illustrate the
      procedure by computing the piezoelectric and nonlinear dielectric susceptibility
      tensors of III-V semiconductors.

PMID- 12225170
TI  - Rabi oscillations in a large Josephson-junction qubit.
AB  - We have designed and operated a circuit based on a large-area current-biased
      Josephson junction whose two lowest energy quantum levels are used to implement a
      solid-state qubit. The circuit allows measurement of the qubit states with a
      fidelity of 85% while providing sufficient decoupling from external sources of
      relaxation and decoherence to allow coherent manipulation of the qubit state, as
      demonstrated by the observation of Rabi oscillations. This qubit circuit is the
      basis of a scalable quantum computer.

PMID- 12225171
TI  - Phase transitions and volunteering in spatial public goods games.
AB  - We present a simple yet effective mechanism promoting cooperation under full
      anonymity by allowing for voluntary participation in public goods games. This
      natural extension leads to "rock-scissors-paper"-type cyclic dominance of the
      three strategies, cooperate, defect, and loner. In spatial settings with players
      arranged on a regular lattice, this results in interesting dynamical properties
      and intriguing spatiotemporal patterns. In particular, variations of the value of
      the public good leads to transitions between one-, two-, and three-strategy
      states which either are in the class of directed percolation or show interesting
      analogies to Ising-type models. Although volunteering is incapable of stabilizing
      cooperation, it efficiently prevents successful spreading of selfish behavior.

PMID- 12225172
TI  - Periodic chirality transformations propagating on bacterial flagella.
AB  - When a helical bacterial flagellum, clamped at one end, is placed in an external
      flow, it has been observed that regions of the flagellum transform to the
      opposite chirality, and travel as pulses down the length of the filament, the
      process repeating periodically [H. Hotani, J. Mol. Biol. 156, 791 (1982)]]. We
      propose a theory for this phenomenon based on a treatment of the flagellum as an
      elastic object with multiple stable configurations. The simplest possible
      implementation of the model accurately reproduces key features seen in
      experiment.

PMID- 12225173
TI  - Comment on "Molecular dynamics study of melting and fcc-bcc transitions in Xe".

PMID- 12225175
TI  - Reaching fermi degeneracy in two-species optical dipole traps.
AB  - We propose the use of a combined optical dipole trap to achieve Fermi degeneracy
      by sympathetic cooling with a different bosonic species. Two far-detuned pairs of
      laser beams focused on the atomic clouds are used to confine the two atomic
      species with different trapping strengths. We show that a deep Fermi degeneracy
      regime can be potentially achieved earlier than Bose-Einstein condensation, as
      discussed in the favorable situation of a 6Li-23Na mixture. This opens up the
      possibility of experimentally investigating a mixture of superfluid Fermi and
      normal Bose gases.

PMID- 12225176
TI  - N-particle N-level singlet States: some properties and applications.
AB  - Three apparently unrelated problems which have no solution using classical tools
      are described: the "N-strangers," "secret sharing," and "liar detection"
      problems. A solution for each of them is proposed. Common to all three solutions
      is the use of quantum states of total spin zero of N spin-(N-1)/2 particles.

PMID- 12225177
TI  - Nonequilibrium effects of anisotropic compression applied to vortex lattices in
      bose-einstein condensates.
AB  - We have studied the dynamics of large vortex lattices in a dilute-gas Bose
      Einstein condensate. While undisturbed lattices have a regular hexagonal
      structure, large-amplitude quadrupolar shape oscillations of the condensate are
      shown to induce a wealth of nonequilibrium lattice dynamics. When exciting an m=
      2 mode, we observe shifting of lattice planes, changes of lattice structure, and
      sheetlike structures in which individual vortices appear to have merged.
      Excitation of an m=+2 mode dissolves the regular lattice, leading to randomly
      arranged but still strictly parallel vortex lines.

PMID- 12225178
TI  - Relation between anomalous and normal diffusion in systems with memory.
AB  - We present a simple criterion based on the Einstein relation for determining
      whether diffusion in systems governed by a generalized Langevin equation with
      long-range memory is normal, superdiffusive, or subdiffusive. We support our
      analysis with numerical simulations.

PMID- 12225179
TI  - Gravitational energy in quadratic-curvature gravities.
AB  - We define energy (E) and compute its values for gravitational systems involving
      terms quadratic in curvature. There are significant differences, both
      conceptually and concretely, from Einstein theory. For D=4, all purely quadratic
      models admit constant curvature vacua with arbitrary Lambda, and E is the
      "cosmological" Abbott-Deser (AD) expression; instead, E always vanishes in flat,
      Lambda=0, background. For combined Einstein-quadratic curvature systems without
      explicit Lambda-term vacuum must be flat space, and E has the usual Arnowitt
      Deser-Misner form. A Lambda-term forces unique de Sitter vacuum, with E the sum
      of contributions from Einstein and quadratic parts to the AD form. We also
      discuss the effects on energy definition of higher curvature terms and of higher
      dimension.

PMID- 12225180
TI  - Photon mass from inflation.
AB  - We consider vacuum polarization from massless scalar electrodynamics in de Sitter
      inflation. The theory exhibits a 3+1 dimensional analog of the Schwinger
      mechanism in which a photon mass is dynamically generated. The mechanism is
      generic for light scalar fields that couple minimally to gravity. The
      nonvanishing of the photon mass during inflation may result in magnetic fields on
      cosmological scales.

PMID- 12225181
TI  - Experimental identification of nonpointlike dark-matter candidates.
AB  - We show that direct dark-matter detection experiments can distinguish between
      pointlike and nonpointlike dark-matter candidates. The shape of the nuclear
      recoil-energy spectrum from pointlike dark-matter particles, e.g., neutralinos,
      is determined by the velocity distribution of dark matter in the galactic halo
      and by nuclear form factors. Typical cross sections of nonpointlike dark matter,
      for example, Q-balls, have a new form factor, which decreases rapidly with the
      recoil energy. A signal from nonpointlike dark matter is expected to peak near
      the experimental threshold and to fall off rapidly at higher energies.

PMID- 12225182
TI  - Electric dipole moments in the limit of heavy superpartners.
AB  - Supersymmetric loop corrections induce potentially large CP-violating couplings
      of the Higgs bosons to nucleons and electrons that do not vanish in the limit of
      heavy superpartners. The Higgs-mediated CP-odd four-fermion operators are
      enhanced by tan((3)beta and induce electric dipole moments of heavy atoms which
      exceed the current experimental bounds for the electroweak scale Higgs masses and
      tan(beta greater, similar 10. If only the first two sfermion generations are
      heavy, the Higgs-mediated contributions typically dominate over the Barr-Zee type
      two-loop diagrams at tan(beta>30.

PMID- 12225183
TI  - Observability of the neutrino charge radius.
AB  - It is shown that the probe-independent charge radius of the neutrino is a
      physical observable; as such, it may be extracted from experiment, at least in
      principle. This is accomplished by expressing a set of experimental nu(mu)-e
      cross sections in terms of the finite charge radius and two additional gauge- and
      renormalization-group-invariant quantities, corresponding to the electroweak
      effective charge and mixing angle.

PMID- 12225184
TI  - Determining the chirality of Yukawa couplings via single charged Higgs boson
      production in polarized photon collisions.
AB  - When the charged Higgs boson is too heavy to be produced in pairs, the
      predominant production mechanism at linear colliders is via the single charged
      Higgs boson production processes, such as e(-)e(+)-->bcH+,taunuH+ and gammagamma-
      >bcH+,taunuH+. We show that the yield of a heavy charged Higgs boson at a
      gammagamma collider is typically 1 or 2 orders of magnitude larger than that at
      an e(-)e(+) collider. Furthermore, a polarized gammagamma collider can determine
      the chirality of the Yukawa couplings of fermions with charged Higgs boson via
      single charged Higgs boson production and, thus, discriminate models of new
      physics.

PMID- 12225185
TI  - Measurement of the positive muon anomalous magnetic moment to 0.7 ppm.
AB  - A higher precision measurement of the anomalous g value, a(mu)=(g-2)/2, for the
      positive muon has been made at the Brookhaven Alternating Gradient Synchrotron,
      based on data collected in the year 2000. The result a(mu(+))=11 659
      204(7)(5)x10(-10) (0.7 ppm) is in good agreement with previous measurements and
      has an error about one-half that of the combined previous data. The present world
      average experimental value is a(mu)(expt)=11 659 203(8)x10(-10) (0.7 ppm).

PMID- 12225187
TI  - Two-proton radioactivity of 45Fe.
AB  - In an experiment at the SISSI-LISE3 facility of GANIL, the decay of the proton
      drip line nucleus 45Fe has been studied. Fragment-implantation events have been
      correlated with radioactive decay events in a 16x16 pixel silicon-strip detector.
      The decay-energy spectrum of 45Fe implants shows a distinct peak at (1.14+/-0.04)
      MeV with a half-life of T(1/2)=(4.7(+3.4)(-1.4)) ms. None of the events in this
      peak is in coincidence with beta particles. For a longer correlation interval,
      daughter decays of the two-proton daughter 43Cr can be observed after 45Fe
      implantation. The decay energy for 45Fe agrees nicely with several theoretical
      predictions for two-proton radioactivity.

PMID- 12225188
TI  - Coupling a single atomic quantum bit to a high finesse optical cavity.
AB  - The quadrupole S(1/2)-D(5/2) optical transition of a single trapped Ca+ ion, well
      suited for encoding a quantum bit of information, is coherently coupled to the
      standing wave field of a high finesse cavity. The coupling is verified by
      observing the ion's response to both spatial and temporal variations of the
      intracavity field. We also achieve deterministic coupling of the cavity mode to
      the ion's vibrational state by selectively exciting vibrational state-changing
      transitions and by controlling the position of the ion in the standing wave field
      with nanometer precision.

PMID- 12225189
TI  - Interference quenching of nu(")=1 vibrational line in resonant photoemission of
      N2: a possibility to obtain geometrical information on the core-excited state.
AB  - An interference quenching of the nu(")=1 vibrational line in the resonant Auger
      decay of N 1s-->pi(*) core-excited N2 is observed and analyzed. The intensity
      ratio between the nu(")=1 and nu(")=0 vibrational levels of the X2Sigma(+)(g)
      final state shows a surprising nonmonotonous variation as a function of frequency
      detuning, going through a minimum with a complete suppression of nu(")=1. We have
      developed a simple model which shows a linear relation between the value of the
      detuning frequency for this minimum and the equilibrium bond distance R(0)(c) of
      the core-excited state. A new way is thus established of determining the
      equilibrium bond distance for the core-excited state with a precision
      deltaR(0)(c)<10(-3) A.

PMID- 12225190
TI  - Breakdown of the spectator model for the OH bonds in studying the H+H2O reaction.
AB  - The time-dependent wave packet method is used to study the exchange and
      abstraction processes for the H+H2O reaction with both OH bonds in the H2O
      reactant treated as reactive bonds in full dimension. The calculation clearly
      shows that it is necessary to treat both OH bonds in this way in order to
      accurately investigate the exchange process. However, for the abstraction
      process, the spectator model works very well. Nonreactive treatment of one OH
      bond by using a few vibrational basis functions or even freezing the bond can
      yield very accurate abstraction reaction probability.

PMID- 12225191
TI  - Properties of small- to medium-sized mercury clusters from a combined ab initio,
      density-functional, and simulated-annealing study.
AB  - Relativistic coupled-cluster and second-order many-body perturbation theories
      were used to construct two- and three-body potentials for the interaction between
      mercury atoms. A subsequent combined simulated-annealing downhill simplex and
      conjugate gradient-optimization procedure gave global minima for mercury clusters
      with up to 30 atoms. The calculations reveal magic cluster numbers of 6, 13, 19,
      23, 26, and 29 atoms. At these cluster sizes, the static dipole polarizability
      obtained from density-functional theory has a minimum. The calculations also
      reveal a fast convergence of the polarizability towards the bulk limit in
      contrast to the singlet-triplet gap or the ionization potential.

PMID- 12225192
TI  - Four-wave mixing of optical and microwave fields.
AB  - We demonstrate degenerate four-wave mixing involving both optical and microwave
      fields. This four-wave mixing process, with fields that differ in frequency by 5
      orders of magnitude, results from stimulated Raman scattering of the optical
      field from an atomic ground-state Zeeman coherence in warm rubidium vapor, which
      is induced and maintained by the microwave field.

PMID- 12225193
TI  - Phase transition theory of many-mode ordering and pulse formation in lasers.
AB  - A novel theory for the ordering of many interacting modes in lasers is presented.
      By exactly solving a Fokker-Planck equation for the distribution of waveforms in
      the laser in steady state, equivalence of the system to a canonical ensemble is
      established, where the role of temperature is taken by amplifier noise. Passive
      mode locking is obtained as a phase transition of the first kind and threshold is
      calculated, employing mean field theory backed up by a numerical study. For zero
      noise, compliance with the existing noiseless theory is shown.

PMID- 12225194
TI  - Two- and three-dimensional oscillons in nonlinear faraday resonance.
AB  - We study 2D and 3D localized oscillating patterns in a simple model system
      exhibiting nonlinear Faraday resonance. The corresponding amplitude equation is
      shown to have exact soliton solutions which are found to be always unstable in
      3D. On the contrary, the 2D solitons are shown to be stable in a certain
      parameter range; hence the damping and parametric driving are capable of
      suppressing the nonlinear blowup and dispersive decay of solitons in two
      dimensions. The negative feedback loop occurs via the enslaving of the soliton's
      phase, coupled to the driver, to its amplitude and width.

PMID- 12225195
TI  - Axial segregation in a cylindrical centrifuge.
AB  - We propose a theory for axial segregation of suspensions of non-neutrally buoyant
      particles in a rotating cylinder. The cylinder is oriented in the horizontal
      plane, so that any axial forces must arise from interparticle interactions. We
      show that the hydrodynamic interaction between pairs of particles produces a
      relative motion in the axial direction, independent of the gravitational force.
      If the particles are denser than the suspending fluid, differential centrifuging
      between particles at different radial positions leads to an at-tractive
      interaction, inducing a rapid growth of axial density perturbations. We suggest
      that this mecha-nism can explain the origin of band formation in rotating
      suspensions of non-neutrally buoyant particles.

PMID- 12225186
TI  - Observation of the eta(c)(2S) in Exclusive B-->KK(S)K-pi(+) Decays.
AB  - We report the observation of a narrow peak in the K(S)K-pi(+) invariant mass
      distribution in a sample of exclusive B-->KK(S)K-pi(+) decays collected with the
      Belle detector at the KEKB asymmetric e(+)e(-) collider. The measured mass of the
      peak is M=3654+/-6(stat)+/-8(syst) MeV/c(2), and we place a 90% confidence level
      upper limit on the width of Gamma<55 MeV/c(2). The properties agree with heavy
      quark potential model expectations for the eta(c)(2S) meson, the n=2 singlet S
      charmonium state.

PMID- 12225196
TI  - Nuclear fusion in collapsing bubbles-is it there? An attempt to repeat the
      observation of nuclear emissions from sonoluminescence.
AB  - We have repeated the experiment of Taleyarkhan et al. [Science 295, 1868 (2002)]]
      in an attempt to detect the emission of neutrons from d-d fusion during bubble
      collapse in deuterated acetone. Using the same cavitation apparatus, a more
      sophisticated data acquisition system, and a larger scintillator detector, we
      find no evidence for 2.5-MeV neutron emission correlated with sonoluminescence
      form collapsing bubbles. Any neutron emission that might occur is at least 4
      orders of magnitude too small to explain the tritium production reported in
      Taleyarkhan et al. as being due to d-d fusion. We show that proper allowance for
      random coincidence rates in such experiments requires the simultaneous
      measurement of the count rates in the individual detectors.

PMID- 12225198
TI  - Levitation of iridium and liquid mercury by ultrasound.
AB  - Single-axis acoustic levitation of the heaviest solid (iridium, rho=22.6 g cm(
      3)) and liquid (mercury, rho=13.6 g cm(-3) on the Earth is achieved by greatly
      enhancing both the levitation force and stability through optimizing the
      geometric parameters of the levitator. The acoustically levitated Pb-Sn eutectic
      alloy melt (rho=8.5 g cm(-3)) is highly undercooled by up to 38 K, which results
      in a microstructural transition of "lamellae-broken lamellae-dendrites." The
      drastic enhancement of levitation capability indicates a broader application
      range of single-axis acoustic levitation.

PMID- 12225197
TI  - Generic sandpile models have directed percolation exponents.
AB  - We study sandpile models with stochastic toppling rules and having sticky grains
      so that with a nonzero probability no toppling occurs, even if the local height
      of pile exceeds the threshold value. Dissipation is introduced by adding a small
      probability of particle loss at each toppling. Generically for the models with a
      preferred direction, the avalanche exponents are those of critical directed
      percolation clusters. For undirected models, avalanche exponents are those of
      directed percolation clusters in one higher dimension.

PMID- 12225199
TI  - Poiseuille advection of chemical reaction fronts.
AB  - Poiseuille flow between parallel plates alters the shapes and velocities of
      chemical reaction fronts. In the narrow-gap limit, the cubic reaction-diffusion
      advection equation predicts a front-velocity correction equal to the gap-averaged
      fluid velocity epsilon. In the singular wide-gap limit, the correction equals the
      midgap fluid velocity 3epsilon/2 when the flow is in the direction of propagation
      of the reaction front, and equals zero for adverse flow of any amplitude for
      which the front has a midgap cusp. Stationary fronts are possible only for
      adverse flow and finite gaps. Experiments are suggested.

PMID- 12225200
TI  - Polymers in 2D turbulence: suppression of large scale fluctuations.
AB  - Small quantities of a long chain molecule or polymer affect two-dimensional
      turbulence in unexpected ways. Their presence inhibits the transfers of energy to
      large scales causing their suppression in the energy density spectrum. This also
      leads to the change of the spectral properties of a passive scalar which turns
      out to be highly sensitive to the presence of energy transfers.

PMID- 12225201
TI  - Nonlocal dynamics of spontaneous imbibition fronts.
AB  - We have studied spontaneous imbibition fronts generated by capillary rise between
      two roughened glass plates, the separation d of which varied between 10 and 50
      microm. Perfect agreement with Washburn's law was obtained. We have determined
      the roughness exponent chi of the fronts, and found chi=0.81+/-0.01 for small
      length scales. Above a certain crossover length xi, it reached chi=0.58+/-0.04,
      as predicted by the quenched noise Kardar-Parisi-Zhang equation. The crossover
      length is found to scale with the plate separation as sqrt[d], as predicted by
      recent models which properly include nonlocal dynamics effects on the front. We
      believe this to be the first clear identification of crossover from nonlocal to
      local dynamics.

PMID- 12225202
TI  - Observation of inverse ion-cyclotron damping induced by parallel-velocity shear.
AB  - The generation of broadband multiharmonic spectra of electrostatic ion-cyclotron
      waves is demonstrated in a magnetized laboratory plasma in which shear in the
      magnetic-field-aligned (parallel) ion flow and a relative parallel electron drift
      are present. Shear correlates with an increased number of harmonics and a
      decreased electron drift speed. Wave and particle measurements indicate that
      cyclotron damping is reduced and even becomes negative. The fluctuations in the
      time domain are spiky, similar to electric-field fluctuations observed both in
      Earth's auroral zone and in numerical simulations.

PMID- 12225203
TI  - Decay of the diocotron rotation and transport in a new low-density asymmetry
      dominated regime.
AB  - The decay of the diocotron rotation was studied in a new regime in which trap
      asymmetries dominate. Decay within a few diocotron periods was observed,
      sometimes orders of magnitude faster than predicted by the traditional
      "rotational pumping" theory. The decay does not conserve angular momentum, and is
      strongest for small, low-density columns. The new regime appears when "magnetron
      like" rotation from the end confinement fields becomes dominant, and appears to
      be associated with errors in these fields. Transition to decay dominated by
      rotational pumping was observed for larger and denser columns. The asymmetry
      dominated transport was also studied, and found to depend linearly on the line
      density (and not the density) over nearly 4 orders of magnitude.

PMID- 12225204
TI  - Can vacancies lubricate dislocation motion in aluminum?
AB  - The interaction of vacancy with dislocations in Al is studied using the
      semidiscrete variational Peierls-Nabarro model with ab initio determined gamma
      surface. For the first time, we confirm theoretically the so-called vacancy
      lubrication effect on dislocation motion in Al, a discovery that can settle a
      long-standing controversy in dislocation theory for fcc metals. We provide
      insights into the lubrication effect by exploring the connection between
      dislocation mobility and its core width. We predict an increased dislocation
      splitting in the presence of vacancy. We find that on average there is a weak
      repulsion between vacancies and dislocations which is independent of dislocation
      character.

PMID- 12225205
TI  - Luxemburg-gorky effect retooled for elastic waves: a mechanism and experimental
      evidence.
AB  - A new mechanism is proposed for the linear and amplitude-dependent dissipation
      due to elastic-wave-crack interaction. We have observed one of its strong
      manifestations in a direct elastic-wave analog of the Luxemburg-Gorky effect
      consisting of the cross modulation of radio waves at the dissipative nonlinearity
      of the ionosphere plasma. The counterpart acoustic mechanism implies, first, a
      drastic enhancement of the thermoelastic coupling at high-compliance
      microdefects, and, second, the high stress-sensitivity of the defects leads to a
      strong stress dependence of the resultant dissipation.

PMID- 12225206
TI  - Formation of quasi-one-dimensional Cu2O structures by in situ oxidation of
      Cu(100).
AB  - Epitaxial Cu2O islands on a Cu(100) surface formed through oxidizing Cu(100)
      films at 600 degrees C in an ultrahigh vacuum transmission electron microscope
      were observed to undergo a shape transition from initially square shaped islands
      to elongated islands at a critical size of approximately 110 nm. Our experimental
      data on the elongation of Cu2O islands agree with the energetic calculations
      based on the balance between surface and interface energies and the elastic
      stress relaxation in the three-dimensional islands. We developed a kinetic model
      based on oxygen surface diffusion that fits well with the observed volume
      evolution of the Cu2O islands.

PMID- 12225208
TI  - Resonant impurity states in the d-density-wave phase.
AB  - We study the electronic structure near impurities in the d-density-wave (DDW)
      state, a possible candidate phase for the pseudogap region of the high
      temperature superconductors. We show that the density of states near a
      nonmagnetic impurity in the DDW state is qualitatively different from that in a
      superconductor with dx(2)(-y(2)) symmetry. Thus, the electronic structure near
      impurities can provide insight into the nature of the two phases recently
      observed by scanning tunneling microscopy experiments in the superconducting
      state of underdoped Bi-2212 compounds.

PMID- 12225207
TI  - Initial stage of carbon incorporation into si(001) and one-dimensional ordering
      of embedded carbon.
AB  - We investigate the initial stage of the C incorporation into Si(001) using
      thermal dissociation of C2H2. The scanning tunneling microscopy shows that C
      induced dimer vacancies (DVs) with depressed adjacent dimers are generated on the
      surface and aligned in the dimer direction, forming the 2xn structure. The ab
      initio pseudopotential calculations reveal that, with the presence of a DV in the
      surface, the alpha site in the fourth subsurface layer directly below the DV is
      the most favorable for the incorporated C atoms. The embedded C atoms align one
      dimensionally due to the interaction which is attractive in neighboring dimer
      rows but repulsive in the same dimer row.

PMID- 12225209
TI  - Intersite coupling effects in a kondo lattice.
AB  - The La dilution of the Kondo lattice CeCoIn5 is studied. The scaling laws found
      for the magnetic susceptibility and the specific heat reveal two well-separated
      energy scales, corresponding to the single-impurity Kondo temperature T(K) and an
      intersite spin-liquid temperature T(*). The Ce-dilute alloy has the expected
      Fermi liquid ground state, while the specific heat and resistivity in the dense
      Kondo regime exhibit non-Fermi-liquid behavior, which scales with T(*). These
      observations indicate that the screening of the magnetic moments in the lattice
      involves antiferromagnetic intersite correlations with a larger energy scale in
      comparison with the Kondo impurity case.

PMID- 12225210
TI  - Violation of the minimum h-h separation "Rule" for metal hydrides.
AB  - Using gradient-corrected, full-potential, density-functional calculations,
      including structural relaxations, it is found that the metal hydrides RTInH1.333
      (R=La, Ce, Pr, or Nd; T= Ni, Pd, or Pt) possess unusually short H-H separations.
      The most extreme value (1.454 A) ever obtained for metal hydrides occurs for
      LaPtInH1.333. This finding violates the empirical rule for metal hydrides, which
      states that the minimum H-H separation is 2 A. The paired, localized, and bosonic
      nature of the electron distribution at the H site are polarized towards La and In
      which reduces the repulsive interaction between negatively charged H atoms. Also,
      R-R interactions contribute to shielding of the repulsive interactions between
      the H atoms.

PMID- 12225212
TI  - Coulomb drag for strongly localized electrons: a pumping mechanism.
AB  - The mutual influence of two layers with strongly localized electrons is exercised
      though the random Coulomb shifts of site energies in one layer caused by electron
      hops in the other layer. We trace how these shifts give rise to a voltage drop in
      the passive layer, when a current is passed through the active layer. We find
      that the microscopic origin of drag lies in the time correlations of the
      occupation numbers of the sites involved in a hop. These correlations are
      neglected within the conventional Miller-Abrahams scheme for calculating the
      hopping resistance.

PMID- 12225211
TI  - Motional ordering of a charge-density wave in the sliding state.
AB  - We have used high-resolution x-ray scattering, in the presence of an applied
      direct current, for studying the correlation lengths in the sliding charge
      density wave (CDW) state. Transport properties were simultaneously measured in
      situ during the experiment. We find that, while the transverse correlation is
      reduced when the CDW moves, the CDW becomes more ordered in the direction of
      motion. This is the first report of a motional ordering process in a periodic
      system other than a vortex lattice.

PMID- 12225213
TI  - Spin disorder scattering in magnetic metallic alloys.
AB  - Anomalous behavior of the resistivity at or just below the Neel temperature in
      antiferromagnetic metals is usually attributed to the formation of superzone
      gaps. However, we find that RMn12-xFex alloys which have no such gaps exhibit a
      similarly anomalous resistivity. We show that electron scattering by
      substitutional spin disorder can account for such behavior of itinerant magnets.
      This mechanism, which has not been studied before, leads to a relaxation rate
      that is proportional to x(12-x)m(2), where m is the staggered magnetization.
      Together with spin fluctuations, phonon, and impurity scattering, it accounts
      well for the resistivity data we obtain for HoMn12-xFex, for 0< or =x< or =9, in
      the temperature range of 4 to 400 K.

PMID- 12225214
TI  - Carbon nanotubes as schottky barrier transistors.
AB  - We show that carbon nanotube transistors operate as unconventional "Schottky
      barrier transistors," in which transistor action occurs primarily by varying the
      contact resistance rather than the channel conductance. Transistor
      characteristics are calculated for both idealized and realistic geometries, and
      scaling behavior is demonstrated. Our results explain a variety of experimental
      observations, including the quite different effects of doping and adsorbed gases.
      The electrode geometry is shown to be crucial for good device performance.

PMID- 12225215
TI  - Epitaxial strain and superconductivity in La2-xSrxCuO4 thin films.
AB  - The report that T(c) was doubled in underdoped La2-xSrxCuO4 films under
      compressive epitaxial strain has stirred great interest. We show that such films
      are extremely sensitive to oxygen intake, even at very low temperature, with
      startling consequences including colossal lattice expansion and a crossover from
      semiconductor to metallic behavior. We can bring T(c) up to 40 K in La2CuO4 films
      on SrTiO3 substrates-without any Sr doping and under tensile strain. On LaSrAlO4
      substrates, we reached T(c)=51.5 K, the highest so far in La2-xSrxCuO4.

PMID- 12225216
TI  - Superconductivity in MgB2: clean or dirty?
AB  - A large number of experimental facts and theoretical arguments favor a two-gap
      model for superconductivity in MgB2. However, this model predicts strong
      suppression of the critical temperature by interband impurity scattering and,
      presumably, a strong correlation between the critical temperature and the
      residual resistivity. No such correlation has been observed. We argue that this
      fact can be understood if the band disparity of the electronic structure is taken
      into account, not only in the superconducting state, but also in normal
      transport.

PMID- 12225217
TI  - Observation of an unconventional metal-insulator transition in overdoped CuO2
      compounds.
AB  - The electron dynamics in the normal state of Bi(2)Sr(2)CaCu(2)O(8+delta) is
      studied by inelastic light scattering over a wide range of doping. A strong
      anisotropy of the electron relaxation is found which cannot be explained by
      single-particle properties alone. The results strongly indicate the presence of
      an unconventional quantum-critical metal-insulator transition where "hot"
      (antinodal) quasiparticles become insulating while "cold" (nodal) quasiparticles
      remain metallic. A phenomenology is developed which allows a quantitative
      understanding of the Raman results and provides a scenario which links single-
      and many-particle properties.

PMID- 12225218
TI  - Dynamical crossover in an Ising spin glass above T(g): a muon-spin-relaxation
      investigation of Fe0.05TiS2.
AB  - We investigate the temperature dependence of the spin-spin dynamical
      autocorrelation function of the Ising spin glass Fe0.05TiS2 through field
      dependent muon-spin lattice relaxation measurements. We successfully analyze the
      results using the Ogielski function, namely, t(-x)exp((-[t/tau](y)) as employed
      in numerical simulations. The experimental estimates of x, y, and tau are
      compared with those from simulations. Our major finding is that in this system
      the correlation function changes its nature from Ogielski to a form
      indistinguishable from pure stretched exponential upon cooling close to T(g),
      indicating a dynamical crossover.

PMID- 12225219
TI  - YbRh2Si2: spin fluctuations in the vicinity of a quantum critical point at low
      magnetic field.
AB  - We report a 29Si NMR study on aligned single crystals of YbRh2Si2 which shows
      behavior characteristic of a quantum critical point (QCP: T(N)-->0). The Knight
      shift K and the nuclear spin-lattice relaxation rate 1/T(1) of Si show a strong
      dependence on the external field H, especially below 5 kOe. At the lowest H used
      in this measurement (H approximately 1.5 kOe), it was found that 1/T(1)T
      continues to increase down to 50 mK, whereas K stays constant with a large
      magnitude below 200 mK. This result strongly suggests the development of
      antiferromagnetic fluctuations with finite q vectors that compete with q=0 spin
      fluctuations in the vicinity of the QCP near H=0.5 kOe.

PMID- 12225220
TI  - Unconventional carrier-mediated ferromagnetism above room temperature in ion
      implanted (Ga, Mn)P:C.
AB  - Ion implantation of Mn ions into hole-doped GaP has been used to induce
      ferromagnetic behavior above room temperature for optimized Mn concentrations
      near 3 at. %. The magnetism is suppressed when the Mn dose is increased or
      decreased away from the 3 at. % value, or when n-type GaP substrates are used. At
      low temperatures the saturated moment is on the order of 1 Bohr magneton, and the
      spin wave stiffness inferred from the Bloch-law T(3/2) dependence of the
      magnetization provides an estimate T(c)=385 K of the Curie temperature that
      exceeds the experimental value, T(c)=270 K. The presence of ferromagnetic
      clusters and hysteresis to temperatures of at least 330 K is attributed to
      disorder and proximity to a metal-insulating transition.

PMID- 12225221
TI  - Unconventional metallic magnetism in LaCrSb3.
AB  - Neutron-diffraction measurements in LaCrSb3 show a coexistence of ferromagnetic
      and antiferromagnetic sublattices below T(C)=126 K, with ordered moments of
      1.65(4) and 0.49(4)mu(B)/formula unit, respectively (T=10 K), and a spin
      reorientation transition at approximately 95 K. No clear peak or step was
      observed in the specific heat at T(C). Coexisting localized and itinerant spins
      are suggested.

PMID- 12225222
TI  - Resonant enhancement of tunneling magnetoresistance in double-barrier magnetic
      heterostructures.
AB  - We show that spin-dependent resonant tunneling can dramatically enhance tunneling
      magnetoresistance. We consider double-barrier structures comprising a
      semiconductor quantum well between two insulating barriers and two ferromagnetic
      electrodes. By tuning the width of the quantum well, the lowest resonant level
      can be moved into the energy interval where the density of states for minority
      spins is zero. This leads to a great enhancement of the magnetoresistance, which
      exhibits a strong maximum as a function of the quantum well width. We demonstrate
      that magnetoresistance exceeding 800% is achievable in
      GaMnAs/AlAs/GaAs/AlAs/GaMnAs double-barrier structures.

PMID- 12225223
TI  - Interlayer magnetic coupling interactions of two ferromagnetic layers by spin
      polarized tunneling.
AB  - Magnetic interactions involving ferromagnetic layers separated by an insulating
      barrier have been studied experimentally on a fully epitaxial hard-soft magnetic
      tunnel junction: Fe/MgO/Fe/Co. For a barrier thickness below 1 nm, a clear
      antiferromagnetic interaction is observed. Moreover, when reducing the MgO
      thickness from 1 to 0.5 nm, the coupling strength increases up to J=-0.26 erg.cm(
      2). This behavior, well fitted by theoretical models, provides an unambiguous
      signature of the interlayer exchange coupling by spin-polarized quantum
      tunneling.

PMID- 12225224
TI  - Dynamics of the electric field-assisted charge carrier photogeneration in ladder
      type poly(para-phenylene) at a low excitation intensity.
AB  - Electric field-assisted charge carrier photogeneration in a ladder-type methyl
      substituted poly(paraphenylene) was investigated by ultrafast absorption
      spectroscopy at low excitation intensity. The dissociation of excitons into
      electron-hole pairs occurs from the vibrationally relaxed excited state
      throughout its lifetime and is caused by the applied electric field, rather than
      by existence of special "dissociation sites." These findings are of importance
      for material choice in device applications.

PMID- 12225225
TI  - Ultrafast dynamics of electron localization and solvation in ice layers on
      Cu(111).
AB  - The femtosecond dynamics of localization and solvation of photoinjected electrons
      in ultrathin layers of amorphous solid H2O and D2O have been studied by time- and
      angle-resolved two-photon-photoelectron spectroscopy. After electron transfer
      from the metal substrate into the conduction band of ice, the excess electron
      localizes within the first 100 fs in a state at 2.9 eV above E(F), which is
      further stabilized by 300 meV on a time scale of 0.5-1 ps due to molecular
      rearrangements in the adlayer. A pronounced change of the solvation dynamics at a
      coverage of approximately 2 bilayers is attributed to different rigidity of the
      solvation shell in the bulk and near the surface of ice.

PMID- 12225226
TI  - Controlling absorption of gamma radiation via nuclear level anticrossing.
AB  - A significant reduction of absorption for single gamma photons has been
      experimentally observed by studying Mossbauer spectra of 57Fe in a FeCO3 crystal.
      The experimental results have been explained in terms of a quantum interference
      effect involving nuclear level anticrossing due to the presence of a combined
      magnetic dipole and electric quadrupole interaction.

PMID- 12225227
TI  - Coulomb "Blockade" of nuclear spin relaxation in quantum dots.
AB  - We study the mechanism of nuclear spin relaxation in quantum dots due to the
      electron exchange with the 2D gas. We show that the nuclear spin relaxation rate
      1/T(1) is dramatically affected by the Coulomb blockade (CB) and can be
      controlled by gate voltage. In the case of strong spin-orbit (SO) coupling the
      relaxation rate is maximal in the CB valleys, whereas for the weak SO coupling
      the maximum of 1/T(1) is near the CB peaks.

PMID- 12225228
TI  - Quantum cloning with an optical fiber amplifier.
AB  - It has been shown theoretically that a light amplifier working on the physical
      principle of stimulated emission should achieve optimal quantum cloning of the
      polarization state of light. We demonstrate close-to-optimal universal quantum
      cloning of polarization in a standard fiber amplifier for telecom wavelengths.
      For cloning 1-->2 we find a fidelity of 0.82, the optimal value being 5 / 6=0.83.

PMID- 12225229
TI  - Peeling process in living cell movement under shear flow.
AB  - We present a direct optical observation of the behavior of the contact area
      between a living cell (Dictyostelium discoideum) and a solid substrate under
      shear flow. It is shown that the membrane is peeled off the substrate. The
      relationship between the peeling velocity and the applied force is obtained
      experimentally and explained from the behavior of individual adhesion bridges.
      The dissipation occurring during the peeling process is explicitly calculated in
      terms of out-of-equilibrium thermodynamics.

PMID- 12225231
TI  - Ultrafast solvent-induced spin-flip and nonadiabatic coupling: ClF in argon
      solids.
AB  - Femtosecond pump-probe spectra show direct evidence for ultrafast solvent-induced
      spin flip in photodissociation-recombination events of ClF, a light diatomic
      molecule, for which the spin-orbit coupling is weak. The bound triplet states
      ((3)Pi) of ClF are probed and the dynamics for excitation to the singlet state
      ((1)Pi(1)) is compared with excitation to the triplet state B((3)Pi(0)). The
      population initially excited to the singlet state (1)Pi(1) is transferred to the
      bound triplet states (3)Pi within tau(f)=0.5 ps. Oscillations in the spectra
      indicate wave packet dynamics with the triplet state period of 300 to 400 fs in
      both cases. According to simulations of F(2)/Ar, most of the initially excited
      singlet state population is converted to repulsive and weakly bound triplet
      states within approximately 60 fs. In the first ps, 40% of the triplet population
      accumulates in the weakly bound (3)Pi states, in good accord with the experiment.

PMID- 12225230
TI  - Electronic structure of wet DNA.
AB  - The electronic properties of a Z-DNA crystal synthesized in the laboratory are
      investigated by means of density-functional theory Car-Parrinello calculations.
      The electronic structure has a gap of only 1.28 eV. This separates a manifold of
      12 occupied states which came from the pi guanine orbitals from the lowest empty
      states in which the electron is transferred to the Na+ from PO-4 groups and water
      molecules. We have evaluated the anisotropic optical conductivity. At low
      frequency the conductivity is dominated by the pi-->Na+ transitions. Our
      calculation demonstrates that the cost of introducing electron holes in wet DNA
      strands could be lower than previously anticipated.

PMID- 12225232
TI  - Statistical mechanics of learning: a variational approach for real data.
AB  - Using a variational technique, we generalize the statistical physics approach of
      learning from random examples to make it applicable to real data. We demonstrate
      the validity and relevance of our method by computing approximate estimators for
      generalization errors that are based on training data alone.

PMID- 12225233
TI  - Light streak tracking of optically trapped thin microdisks.
AB  - Nonspherical particles can uniquely probe soft system dynamics. We show that
      laser tweezers stably trap thin coinlike microdisks in 3D with an edge-on
      orientation. Scattered light forms a streak that we track using a fast camera to
      measure the disk's angular displacement. Linearly polarized tweezers rotationally
      trap a birefringent disk, and we measure its harmonically bound Brownian rotation
      over 5 decades in time. Near a surface, the disk exhibits a translational
      orientational switchback oscillation. Circularly polarized tweezers rotate the
      disk and streak, yielding a colloidal lighthouse.

PMID- 12225234
TI  - Observation of chaotic dynamics in a powerful backward-wave oscillator.
AB  - Self-modulation regimes of generation in a powerful 10-micros X-band backward
      wave oscillator were studied theoretically and experimentally. The sequence of
      the self-modulation patterns and corresponding bifurcation values observed as the
      current was increased were in good agreement with the results of simulations. It
      was found that at a current of 120 A chaotic self-modulation set in at a power of
      2 MW and a relative spectral width of 4%.

PMID- 12225235
TI  - Epidemic threshold in structured scale-free networks.
AB  - We analyze the spreading of viruses in scale-free networks with high clustering
      and degree correlations, as found in the Internet graph. For the susceptible
      infected-susceptible model of epidemics the prevalence undergoes a phase
      transition at a finite threshold of the transmission probability. Comparing with
      the absence of a finite threshold in networks with purely random wiring, our
      result suggests that high clustering (modularity) and degree correlations protect
      scale-free networks against the spreading of viruses. We introduce and verify a
      quantitative description of the epidemic threshold based on the connectivity of
      the neighborhoods of the hubs.

PMID- 12225236
TI  - Comment on "Reaction imaging with interferometry".

PMID- 12225238
TI  - Comment on "Critical dynamics of a vortex-loop model for the superconducting
      transition".

PMID- 12225240
TI  - Comment on "Disorder and quantum fluctuations in superconducting films in strong
      magnetic fields".

PMID- 12225242
TI  - Anti-obesity drug development.
AB  - Obesity accelerates morbidity and mortality and has been described by the World
      Health Organization (WHO) as an epidemic in many industrialised nations
      [101,102]. Diet, exercise and lifestyle recommendations have proven to be mostly
      ineffective in adequately preventing or treating the progression of this public
      health disease. Existing drug treatment is limited by the scarce number of safe
      and well-tolerated drugs with proven long-term efficacy in maintaining weight
      loss. Numerous anti-obesity drugs in development have promise. Yet, despite that
      obesity is the single most common nutritional problem in many developed nations
      and despite the devastating health consequences of this unchecked epidemic,
      investigational anti-obesity drugs face unique and significant challenges due to
      past and current experiences with anti-obesity drugs. It is anticipated that new
      anti-obesity drugs for this serious, multifaceted metabolic disease will become
      as safe and effective and as medically accepted as the treatment of other
      metabolic disorders such as hypertension, dyslipidaemia or Type 2 diabetes
      mellitus. This may be particularly important, given that these metabolic
      disorders may be largely due to or exacerbated by obesity itself.

PMID- 12225243
TI  - Advanced glycation end products and diabetic complications.
AB  - Diabetic complications are major cause of morbidity and mortality in patients
      with diabetes. While the precise pathogenic mechanism(s) underlying conditions
      such as diabetic retinopathy, diabetic nephropathy and increased risk of
      atherosclerosis remain ill-defined, it is clear that hyperglycaemia is a primary
      factor that initiates and promotes complications. Formation of advanced glycation
      end products (AGEs) correlate with glycaemic control, and these reactive adducts
      form on DNA, lipids and proteins where they represent pathophysiological
      modifications that precipitate dysfunction at a cellular and molecular level.
      Many of these adducts form rapidly during diabetes and promote progression of a
      raft of diabetes-related complications. Recent evidence also suggests an
      important interaction with other pathogenic mechanisms activated within the
      diabetic milieu. This review outlines the nature of AGE formation in biological
      systems and highlights accumulative evidence that implicates these adducts in
      diabetic complications. As more therapeutic agents are developed to inhibit AGE
      formation or limit their pathogenic influence during chronic diabetes, it is
      becoming clear that these anti-AGE strategies have an important role to play in
      the treatment of diabetic patients.

PMID- 12225244
TI  - The development of contraceptive vaccines.
AB  - The use of vaccination as a means of controlling fertility was established during
      the last decade with the publication of a successful Phase II trial demonstrating
      the efficacy of this approach to family planning. However, only this one Phase II
      trial has been completed despite a plethora of hormonal and gamete antigens that
      have been proposed as candidate vaccines. Improvements in the design and
      formulation of contraceptive vaccines are underway and will be a necessary
      prelude to further clinical trials.

PMID- 12225245
TI  - New developments in contraceptive drugs for use by women.
AB  - Since the oral contraceptive pill was first marketed in 1959, advances in
      contraceptive drugs for women have been limited to variations on the theme of
      oestrogen in combination with progestogen or progestogen alone. Alterations to
      the pill regimen, new progestogens and new delivery systems have increased choice
      but while these advances significantly improve acceptability, side effects and
      risks remain essentially unchanged. New ideas are in short supply.
      Antiprogesterones offer a new approach with a variety of dose regimens but their
      development has been seriously hampered by the politics associated with their
      abortifacient action. Other hormone antagonists as contraceptives seem a long way
      off. Immunocontraception is still at a very early stage. Genes, whose products
      are uniquely concerned with reproductive processes, promise new targets but
      radically new contraceptive drugs for women appear distant.

PMID- 12225246
TI  - Therapeutic potential of GnRH antagonists in the treatment of precocious puberty.
AB  - Pituitary-gonadal axis activation depends upon pulsatile hypothalamic
      gonadotropin-releasing hormone (GnRH) secretion. This phenomenon has led to
      clinical use of GnRH agonists in the treatment of central precocious puberty.
      GnRH analogues contain substitutions of the native decapeptide. Depending upon
      the substitutions, the analogues have GnRH agonistic or antagonistic properties.
      The pharmacokinetics of GnRH agonists, the established treatment of precocious
      puberty, includes an initial 'flare-up' of the pituitary-gonadal axis, followed
      by a reduced luteinising hormone secretion by desensitisation of pituitary GnRH
      receptors. Antagonistic GnRH analogues act by competitive binding to the
      pituitary GnRH receptors, thereby preventing the action of endogenous GnRH -
      theoretically offering a more direct and dose-dependent treatment alternative.
      The antagonist available today in Germany is a concomitant in assisted
      reproduction with only 1 - 3 days duration. However, long-acting depot
      preparations of other GnRH antagonists are in primate-testing phase. Our animal
      tests indicate strong potential for the development and testing of long-acting
      depot preparations of GnRH antagonists in treating precocious puberty.

PMID- 12225247
TI  - Selenium-based pharmacological agents: an update.
AB  - The biochemistry and pharmacology of selenium is a subject of intense current
      interest, particularly from the viewpoint of public health. Selenium, long
      recognised as a dietary antioxidant, is now known to be an essential component of
      the active sites of several enzymes, including glutathione peroxidase and
      thioredoxin reductase, which catalyse reactions essential to the protection of
      cellular components against oxidative and free radical damage. A low
      concentration of selenium in plasma has been identified as a risk factor for
      several diseases, including cancer, cardiovascular disease, osteoarthritis and
      AIDS, and several large-scale selenium supplementation human trials are now
      underway. Evidence is emerging that, at least in the case of cancer, the
      antitumorigenic effect of selenium supplementation arises at least in part from
      enhanced production of specific selenium-containing metabolites, not just from
      maximal expression of selenoenzymes. Therefore a number of novel pharmaceutical
      agents which are selenium-based or which target specific aspects of selenium
      metabolism are under development. Among these are orally-active antihypertensive
      agents, anticancer, antiviral, immunosuppressive and antimicrobial agents, and
      organoselenium compounds which reduce oxidative tissue damage and edema. It can
      be anticipated that as our understanding of the basic biology and biochemistry of
      selenium increases, the coming years will bring further development of new
      selenium-based pharmaceutical agents with therapeutic potential toward a variety
      of human diseases.

PMID- 12225248
TI  - Novel therapeutics for the treatment of graft-versus-host disease.
AB  - Acute graft-versus-host disease (GVHD) and chronic GVHD remain the major barriers
      to successful haematopoietic cell transplantation. The induction of GVHD may be
      divided into three phases: recipient conditioning, donor T cell activation and
      effector cells mediating GVHD. This review examines GVHD prevention and treatment
      using this conceptual model as framework. The various pharmacological agents
      discussed impact on different phases of the GVHD cascade. For example,
      keratinocyte growth factor and IL-11 are cytokines that may be useful in
      disrupting Phase I of the GVHD cascade by blocking gastrointestinal tract damage
      and lowering serum levels of lipopolysaccharide and TNF-alpha. Cyclosporin, FK506
      and sirolimus are some of the main agents that disrupt Phase II (donor T cell
      activation). Mycophenolate mofetil likely acts on this phase as well. Other novel
      drugs that affect Phase II are tolerance-induction agents such as cytotoxic T
      lymphocyte antigen (CTLA)-4 Ig and anti-CD40 ligand, and preliminary results
      using CTLA-4 Ig in GVHD prevention are encouraging. Two exciting agents that
      appear to affect only activated lymphocytes are ABX-CBL and visilizumab. Examples
      of agents that disrupt Phase III are the IL-2 receptor antagonist daclizumab and
      the anti-TNF-alpha monoclonal antibody infliximab. These anticytokine antibodies
      have shown promising results in early studies. The most effective approach to
      GVHD prevention will likely be a combination regimen where the three phases of
      the GVHD cascade are disrupted. Once GVHD has occurred, all three phases of the
      cascade are activated. Developments of combination therapy for treatment of both
      acute and chronic GVHD will likely yield better results than monotherapy. The
      numerous new treatment modalities presented should improve the outlook for acute
      and chronic GVHD.

PMID- 12225249
TI  - Investigational pharmacologic treatment for liver disease.
AB  - Liver disease can cause significant morbidity and mortality. Few pharmacological
      options exist for these diseases, however, new agents are in development and
      older agents are being evaluated for new indications. Several new nucleoside and
      nucleotide analogues are being developed to treat hepatitis B virus infection.
      Pegylated interferons have been developed for hepatitis C infection.
      Ursodeoxycholic acid has recently been implicated in the treatment of liver
      disease, including non-alcoholic steatohepatitis and primary sclerosing
      cholangitis.

PMID- 12225250
TI  - Atazanavir: a novel HIV-1 protease inhibitor.
AB  - The introduction of HIV-1 protease inhibitors in 1995 ushered in the era of
      highly active antiretroviral therapy. For the first time, inhibition of two key
      enzymes responsible for HIV replication, reverse transcriptase and protease, was
      possible. The combination of two nucleoside reverse transcriptase inhibitors with
      a single protease inhibitor proved highly effective at reducing viral burden. In
      resource-rich countries where such combination therapy is readily available,
      dramatic reductions in HIV-related morbidity and mortality have been seen.
      However, long-term use of highly active antiretroviral therapy has led to several
      issues, including development of drug resistance and metabolic complications.
      Atazanavir (formerly BMS-232632), a novel azapeptide protease inhibitor, is a
      potent protease inhibitor that is not associated with significant dyslipidaemia
      as seen with other protease inhibitors. In this review, the current standard
      approach to the treatment of HIV in the US will be discussed as background to
      understand the potential utility of this new antiretroviral agent.

PMID- 12225251
TI  - Potential benefit and limitations of a broad access to potent antiretroviral
      therapy in developing countries.
AB  - In industrialised countries, highly active antiretroviral therapy (HAART) has
      drastically reduced HIV mortality. Only few developing countries have introduced
      HAART on a large scale, leaving millions of HIV-infected individuals without life
      saving therapy. Although HAART appears to be economically viable for middle
      income countries, it remains unaffordable for many of the poorest and worst
      affected nations. In response, significant discounts for antiretrovirals and debt
      relief have been granted. Apart from economic problems, other important issues
      need to be addressed before antiretroviral therapy can be optimally utilised,
      including the logistics of drug supply, HIV education for hospital staff and
      patients, and laboratory facilities that allow clinicians to assess the efficacy
      of HAART.

PMID- 12225252
TI  - Early childhood asthma.

PMID- 12225253
TI  - Definitions and early natural history.
AB  - What we know: Asthma is a disease of mucosal and immunological development. If a
      child's first episode of wheeze occurs in the first year of life, the child has
      about a 50% chance of developing asthma. If a child develops recurrent wheeze,
      the probability that it is related to asthma rises to about 80%. The presence of
      atopy, positive allergen skin-prick tests or elevated IgE antibody levels
      increases the probability of asthma to over 95%. Evidence of changes in lung
      function or of inflammation confirms a diagnosis of asthma. What we need to know:
      Can an algorithm be created for general practitioners to predict the likelihood
      of the development of asthma on the basis of presenting symptoms and relevant
      investigations? Is it feasible to use regular lung function testing or induced
      sputum samples to monitor the development of asthma in early childhood? How can
      we better understand in-utero programming for asthma? What characteristics of
      airway mucosal maturation are associated with the development of asthma? What
      deviations from normal immunological development are associated with the
      development of asthma?

PMID- 12225254
TI  - Risk factors and epidemiology.
AB  - What we know: No one gene is a major cause of asthma. Some racial groups are more
      at risk of asthma than others. Early exposure to domestic animals appears to
      reduce the chance of developing asthma. Good hygiene may increase the likelihood
      of asthma. Impaired early airway function predisposes to asthma. What we need to
      know: How do several minor genetic factors combine to increase the risk of asthma
      in individuals and in population groups? Does early exposure to allergens promote
      sensitisation or tolerance? How do viruses precipitate asthma? Can acute asthma
      be treated by treating viral respiratory infections? Does impaired early airway
      function predispose to asthma throughout childhood?

PMID- 12225255
TI  - Long-term outcome of childhood asthma.
AB  - What we know: The outcome of childhood asthma is dependent on the pattern of
      asthma through childhood. Episodic asthma in childhood tends to resolve in
      adolescence and through mid-adult years, with no impairment of lung function.
      Persistent asthma in childhood is more likely to persist into adult years, with
      modest impairment of lung function. The impairment of lung function occurs early
      in the disease process and is not progressive, despite continuing symptoms. What
      we need to know: Are there clearly identifiable phenotypes of childhood asthma
      that have different aetiologies, response to treatment, genotypes and natural
      history? Does early treatment with anti-inflammatory agents prevent impairment of
      lung function? Can an algorithm be developed to predict the likelihood of
      persistent asthma on first presentation?

PMID- 12225256
TI  - The contribution of airway structure to early childhood asthma.
AB  - What we know: Airway inflammation and remodelling of the airway wall play an
      important role in the pathophysiology of asthma in adults. There is a paucity of
      information regarding the pathology of asthma in early childhood. Postmortem and
      biopsy studies of children with asthma have consistently shown an increase in the
      size of mucous glands, but an increase in smooth muscle is seen only in some
      cases. Biopsy studies indicate that the airways of children with asthma are
      inflamed, although the infiltrate may be more lymphocytic than eosinophilic in
      nature. As children's lungs grow rapidly in the first few years, the impact of
      structural changes in the airways may have a more profound physiological impact
      at this time than later in life. What we need to know: Is the pathology of asthma
      the same in children and adults? Is it the same in mild, moderate and severe
      asthma? Can bronchoscopy and airway biopsy provide us with information about the
      pathology of early childhood asthma? Can the more advanced imaging techniques
      available today, such as spiral computed tomography and the use of inhaled gases
      of various densities, assist in elucidating the pathology of early childhood
      asthma? Can non-invasive techniques, such as measurement of exhaled gases,
      provide us with accurate information about inflammation and the pathology of
      early childhood asthma? What are the real ethical and practical limitations to
      studying the pathology of early childhood asthma?

PMID- 12225257
TI  - The immunobiology of early asthma.
AB  - What do we know? CD4+ T cells are strongly implicated in asthma pathogenesis. The
      "T(H)2 hypothesis" postulates two patterns of cytokine secretion by stimulated
      CD4+ T cells: a "T(H)1" response and a "T(H)2" response. T(H)2-type cytokines
      (interleukins IL-4, IL-5, IL-9, IL-13) regulate eosinophilia, mast cell growth,
      IgE and mucus production and have been proposed as key regulatory factors in
      asthma. T(H)1-type cytokines include interferon-gamma, IL-2, IL-12, IL-18, and
      tumour necrosis factor beta.T(H)2 responses are reciprocally inhibited by T(H)1
      responses in animal models, but this may not be so in asthma in humans. In
      humans, T(H)1- and T(H)2-type cytokines are often coexpressed in early asthma.
      What do we need to know? Is cross-regulation between T(H)1 and T(H)2 immune
      biases truly lost in in early asthma? Can induction of T(H)1-type responses
      actually protect against asthma, as predicted by the "hygiene hypothesis"? If so,
      how might this induction be achieved safely in infants? Can the in-utero
      environment be subtly manipulated to minimise asthma risk? Does early childhood
      treatment with current anti-asthma drugs lead to long-term immune changes?

PMID- 12225258
TI  - Respiratory infections and asthma.
AB  - What we know: Respiratory viral infections caused by rhinoviruses, coronaviruses,
      influenza, parainfluenza and respiratory syncytial viruses (RSVs) are important
      triggers of asthma attacks. Mycoplasma and Chlamydia infections can also provoke
      asthma attacks, although less commonly. RSV infections probably do not cause
      asthma, but are potent triggers of wheezing, with the result that RSV infection
      often reveals underlying asthma in children. RSV infection does not cause atopy.
      Bacterial respiratory infections in infancy appear to protect against later
      atopy. What we need to know: Does RSV infection in infancy alter a child's
      T(H)1/T(H)2 responses to later infections with other respiratory pathogens? What
      are the mechanisms (immunological or mechanical) by which respiratory pathogens
      cause wheezing? What is the role of respiratory infections in exacerbations of
      asthma? Can epidemiology shed light on this? Do viruses such as RSV cause asthma
      or uncover underlying asthma? Do children respond differently to RSV than to
      other viruses? Does atopy affect those responses? Do bacterial respiratory
      infections truly protect against future atopy?

PMID- 12225259
TI  - Do allergens play a role in early childhood asthma?
AB  - What we know: Sensitisation to indoor allergens (house-dust mite, cat) is related
      to the level of exposure to these allergens in early childhood. The prevalence of
      asthma in childhood is independent of allergen exposure in early life. Asthma
      occurs in a substantial number of young children in the absence of allergen
      sensitisation. Asthma and allergic sensitisation have increased in recent
      decades, but there is no conclusive evidence that this is due to changes in
      environmental allergens. What we need to know: Have changes in environmental
      allergens contributed to the increasing incidence of asthma in recent decades? Is
      early childhood asthma (or certain subtypes of asthma) an allergen-induced
      disease? Is it possible to modify asthma by environmental allergen manipulation
      in early childhood? Is it possible to modulate the immune response to allergens
      in a favourable direction in early childhood?

PMID- 12225260
TI  - Pulmonary physiology, airway responsiveness and asthma.
AB  - What we know: Tests that have allowed the measurement of lung function in infants
      have greatly enhanced our understanding of early pulmonary development and the
      pathophysiology of early respiratory disease. Airway responsiveness in infancy
      appears to be an independent determinant of symptoms and lung function later in
      childhood. New tests of airway responsiveness hold the promise of predicting,
      with increased specificity, infants at risk of developing asthma. What we need to
      know: What are the factors that determine airway responsiveness soon after birth?
      Why does airway responsiveness in the first weeks of life relate to lung function
      many years later? Do different challenge agents reflect different
      pathophysiological processes involved in the development of persistent asthma?

PMID- 12225261
TI  - Invasive monitoring of airway inflammation.
AB  - What we know: Ethical concerns have limited research involving invasive
      bronchoscopy techniques in young children. No longitudinal studies have been
      conducted to compare the findings of bronchial biopsy or bronchoalveolar lavage
      in young children with transient episodic wheeze versus asthma. Children with
      atopic asthma have more airway eosinophils and mast cells than children with
      viral-associated wheeze. Both neutrophilic and eosinophilic patterns of
      inflammation are present in asthma. What we need to know: Can we establish robust
      normal values for tissue and fluid samples obtained at bronchoscopy or
      bronchoalveolar lavage? Do biopsy specimens taken at the carina tell us about the
      pathological processes occurring in asthma? Can we use invasive procedures to
      predict which children with wheeze will continue to wheeze and develop a
      classical asthma phenotype? Can we use invasive procedures to guide asthma
      therapy? Can we expect airway inflammation to resolve with anti-inflammatory
      medication? Can we correlate invasive with non-invasive measures of inflammation?
      Can we use our understanding of pro- and anti-inflammatory pathways to develop
      new therapeutic interventions? Is there a presymptomatic phase of inflammation?

PMID- 12225262
TI  - Non-invasive monitoring of airway inflammation.
AB  - What we know: Various techniques are available that purport to measure aspects of
      airway inflammation non-invasively, including analysis of volatile molecules in
      exhaled breath and components of breath condensates. Adapting and validating
      these methods for use in young children and infants poses significant
      methodological problems, but progress has been made, particularly with regard to
      measurements of exhaled nitric oxide. Future studies to validate such tests are
      likely to require access to airway tissue for examination as a "gold standard".
      What we need to know: How can we obtain airway tissue from infants and young
      children to better characterise the early airway changes in asthma? How do non
      invasive tests of airway inflammation compare with a validated gold standard? How
      sensitive and specific are non-invasive tests of inflammation for predicting
      outcomes in asthma, including response to therapy?

PMID- 12225263
TI  - Exercise-induced asthma in children: a marker of airway inflammation.
AB  - What we know: Exercise-induced asthma (EIA) occurs in up to 23% of
      schoolchildren. In 40% of children with demonstrable EIA, no clinical diagnosis
      of asthma has been made. Children with asthma and EIA have eosinophils in their
      sputum, consistent with active asthma. EIA is well controlled in 50%-65% of
      children with moderate to severe asthma, so that only a minority will need
      prophylactic therapy immediately before exercise. Beta(2)-agonists are not the
      most suitable therapy for preventing EIA if they need to be used on a daily
      basis. The severity of EIA appears to be an indirect index of the severity of
      airway inflammation. What we need to know: Do non-symptomatic children with EIA
      require treatment for asthma? Does failure to identify and treat children unaware
      of their airways narrowing after exercise lead to airflow limitation in the long
      term, particularly in the small airways? Can exercise, or surrogate tests used to
      identify EIA, also be used to assess children with asthma? What is the minimum
      dose of steroid required to inhibit EIA, as high doses of steroids may be
      inappropriate in children? What is the best prophylactic treatment for EIA in
      children whose asthma is otherwise well controlled by inhaled steroids? What is
      the best prophylactic treatment for EIA in children with frequent episodic asthma
      or mild persistent asthma? Are leukotriene antagonists alone better than beta(2)
      agonists alone in preventing EIA throughout the day? How many children taking
      long-acting beta(2)-agonists twice daily, either alone or in combination with an
      inhaled steroid, experience breakthrough EIA during school and require rescue
      medication?

PMID- 12225264
TI  - Current drug therapies: relievers and preventers.
AB  - What we know: The different wheezing phenotypes in early childhood may influence
      the response to therapy. beta-Agonists are effective in acute asthma from the
      first year of life and anticholinergics have been shown to provide additional
      benefit from at least 18 months of age. Non-steroidal preventer medications
      provide some benefit in early childhood asthma, but response is variable and
      dependent on severity. Inhaled corticosteroids are the most effective preventer
      medication in children with persistent asthma, but have not been shown to be
      effective in children with episodic viral wheeze. There is no convincing evidence
      to suggest that inhaled corticosteroids influence long-term outcome in childhood
      asthma. What we need to know: Can we distinguish different wheezing phenotypes at
      presentation (using clinical features or other markers of airway inflammation or
      airway hyperresponsiveness) in order to target therapy? What are the relative
      benefits of reliever and preventer medications in treating different wheezing
      phenotypes, and do all wheezing phenotypes require treatment? What is the dose
      response curve for inhaled corticosteroids in infants and young children with
      asthma? Are infants and young children more susceptible than older children to
      growth suppression or other side effects from inhaled corticosteroids? Can early
      treatment with inhaled corticosteroids or non-steroidal medications influence
      long-term outcome in terms of asthma development and/or loss of lung function?

PMID- 12225265
TI  - Therapeutic prospects for early asthma.
AB  - What we know: There is strong evidence that T cells contribute to asthma
      pathogenesis. Immune-modulating drugs that dampen, turn off or redirect T cells,
      and adjuvants that trigger T(H)1 immune responses, are potential therapies for
      preventing asthma. Current T cell immune suppressors are too toxic to use in very
      young children with asthma. Immune-modulation research is identifying pathways
      that might lead to preventive therapy for asthma. Inhibitors of T cell cytokines
      do not reduce asthma in adults. What we need to know: Is immune deviation from a
      T(H)2-type response towards a T(H)1-type response a sound strategy given that
      mixed T(H)1/T(H)2 responses are already known to occur in asthma? What,
      specifically, triggers the development of armed effector lymphocytes that are
      thought to cause tissue damage in asthma? Are the changes in lung structure that
      are observed in chronic asthma really dependent on T cell mechanisms? Can
      abnormal lung structure be improved or normalised? Would any of these strategies
      be safer and more effective than current therapies?

PMID- 12225266
TI  - Drug delivery.
AB  - What we know: In preschool children, small-volume spacers perform better than
      large-volume spacers. Detergent is the best antistatic agent for spacers,
      increasing lung delivery two- to threefold, but it must not be rinsed off. A
      mouthpiece should be used in children aged 2-3 years or older, as lung delivery
      is two- to threefold higher for oral inhalation than nasal inhalation (ie, by
      mask). Inhaled drug doses do not generally need to be reduced in infants and
      young children owing to inefficiencies of delivery in younger patients.
      Nebulisers are "dinosaurs" and not needed for most children with asthma. What we
      need to know: What is the best inhalation technique for spacers? How long should
      children breathe, how many breaths should they take, and at what age should they
      breath-hold? How should children, parents and doctors be instructed to achieve
      optimal levels of electrostatic charge reduction for spacers? How much should
      inhaled steroid dose be reduced when a spacer is used optimally? What dosing
      instructions should be given for beta(2)-agonists delivered by spacer?

PMID- 12225267
TI  - Action plans, self-monitoring and adherence: changing behaviour to promote better
      self-management.
AB  - What we know: Patient self-management improves asthma outcomes. The key features
      of self-management are having a written asthma action plan, monitoring asthma
      symptoms and seeking regular review. Self-management is an important goal.
      Doctors can learn how to improve patient self-management. Multiple attitudinal
      barriers limit adherence to asthma preventers, especially inhaled corticosteroids
      in children. Appointment reminders improve clinic attendance. Poor adherence with
      the asthma treatment regimen is common. Simplification of the healthcare regimen
      is associated with better adherence. What we need to know: What is it about a
      written action plan that is the key to its effect? Is it mostly useful for
      managing acute asthma exacerbations or is it also useful for day-to-day
      management in the longer term? How can broader implementation of action plans be
      achieved in Australia? How can appointment reminders be incorporated into regular
      medical care? How can we modify patient attitudinal and knowledge barriers to
      preventer medication? How can we improve compliance with asthma preventer
      medication?

PMID- 12225268
TI  - Is prevention of childhood asthma possible? Allergens, infections and animals.
AB  - What we know: Epidemiological studies have identified a number of factors
      associated with increased incidence of asthma. These include allergen
      sensitisation and exposure, reduced exposure to infections and to farm animals in
      early childhood, and maternal smoking. These factors may represent "true" risk
      factors for asthma or may be merely associated factors that do not in themselves
      cause asthma. The "hygiene hypothesis" has been proposed as one mechanism by
      which infections may protect against asthma. Current recommendations for the
      primary prevention of asthma include exclusive breastfeeding for the first six
      months of life, avoidance of maternal smoking during pregnancy and infancy, and
      reducing the levels of house-dust mite in some environments. What we need to
      know: What are the mechanisms by which specific risk factors and prevention
      strategies lead to or protect from asthma? How do genetic and environmental
      factors interact to increase the risk of asthma?

PMID- 12225269
TI  - Is asthma prevention possible with dietary manipulation?
AB  - What we know: Primary prevention of asthma should be possible because the recent
      increase in asthma is due to environmental factors. The major modifiable dietary
      environmental risk factors for childhood asthma are lack of breastfeeding and low
      intake of omega-3 fatty acids. Randomised controlled trials (RCTs) have shown
      that interventions using probiotics, hydrolysed milk formulas, and combined
      dietary manipulation plus airborne allergen avoidance reduce asthma and/or atopy
      in newborns. Observational studies have shown a 30%-50% reduction in childhood
      asthma with exclusive breastfeeding for three months, and similar reductions in
      children who eat fish regularly (ie, have a high intake of omega-3 fatty acids).
      What we need to know: Will further RCTs using intervention with probiotics reveal
      identifiable subgroups of children who respond and children who do not respond?
      Will supplementation of the diet with omega-3 oil reduce the rate of significant
      clinical atopic disease, particularly asthma? If so, for how long will
      supplements need to be given? Will effective primary prevention require multiple
      intervention strategies? If so, how feasible are these as public health
      interventions? What are the benefits and harms of allergen-avoidance diets in
      high-risk women who are breastfeeding? Can protein hydrolysate formulas reduce
      rates of atopy and/or asthma?

PMID- 12225270
TI  - Surviving cardiac arrest.

PMID- 12225271
TI  - Drug advertising: truths, half-truths and few statistics.

PMID- 12225272
TI  - Broadening the focus of research into the health of Indigenous Australians.

PMID- 12225273
TI  - Inhaled steroids - too much of a good thing?

PMID- 12225274
TI  - Pharmaceutical advertisement claims in Australian medical publications.
AB  - OBJECTIVE: To determine the quality of claims in advertisements published in
      Australian medical publications, describe how benefits and harms are presented,
      and examine the level of underpinning evidence. DESIGN AND SETTING: Audit of a
      consecutive three-month sample of advertisements appearing in six popular
      Australian medical publications. MAIN OUTCOME MEASURES: Proportion of
      advertisements with quantitative information; proportion of claims conveying
      clinical outcomes; where retrievable, level of underpinning evidence. RESULTS: Of
      1504 claims, 855 could be substantiated quantitatively. Of these, 45% were
      supported by compelling evidence (randomised controlled trials or better). Of 13
      claims explicitly reporting quantitative outcomes, none provided the absolute
      risk reduction or the number needed to treat. CONCLUSIONS: Our audit invites
      greater diligence by pharmaceutical companies in substantiating their claims and
      greater vigilance among clinicians when reading them.

PMID- 12225275
TI  - Patients' views of the burden of asthma: a qualitative study.
AB  - OBJECTIVES: To explore the burden of asthma on the lives of people presenting to
      hospital emergency departments for asthma treatment. DESIGN: A qualitative study.
      Consenting individuals with asthma who presented to emergency departments were
      interviewed in-depth, and interviews were taped, transcribed and thematically
      analysed. Questionnaire data on medication use, respiratory health and asthma
      knowledge were also collected. Asthma severity was determined from the medical
      records. SETTING: A tertiary teaching hospital and a suburban hospital during
      March and April 2000, and a rural hospital during July and August 2000.
      PARTICIPANTS: Sixty-two participants (19 male and 43 female), aged 18-70 years.
      RESULTS: The burden of asthma was broad, affecting social life, personal
      relationships, employment and finances. The cost of asthma medication was an
      issue for nearly two-thirds of participants. Individuals performed their own
      "cost-benefit analysis" for medication use, weighing up expense, perceived side
      effects and potential benefits. As a consequence, several participants chose to
      alter their medication dose, or not to take prescribed medications. For some
      participants, asthma directly contributed to diminished employment opportunities.
      CONCLUSIONS: To achieve a therapeutic partnership, doctors need to be aware of
      the substantial social, personal and financial burden of asthma for their
      patients. They should also recognise that patients' perceptions of treatment cost
      may compromise treatment adherence.

PMID- 12225276
TI  - Assault-related admissions to hospital in Central Australia.
AB  - OBJECTIVE: To determine the number of assault-related admissions to hospital in
      the Central Australia region of the Northern Territory over a six-year period.
      DESIGN AND SETTING: Retrospective analysis of all patients admitted to Alice
      Springs Hospital (ASH) and Tennant Creek Hospital (TCH) from July 1995 to June
      2001, where the primary cause of injury was "assault". MAIN OUTCOME MEASURES:
      Frequency of assault-related admission to hospital; demographic characteristics
      of the victims. RESULTS: In the six years, there were 2449 assault-related
      admissions to ASH and 545 to TCH. Adults aged 25-34 years were most frequently
      hospitalised for assault, in a proportion greater than their proportion in the NT
      population. Females represented 59.7% of people admitted to ASH and 54.7% to TCH,
      greater than their proportion in the NT population. Aboriginals comprised 95.2%
      of ASH and 89.0% of TCH admissions, and were admitted in a significantly greater
      proportion than their proportion in the NT population (P < 0.001). The age
      adjusted hospital admission rate resulting from assault has increased (P = 0.002)
      at an average rate of 1.6 (SE, 0.2) per 10 000 people per year. The proportion of
      assault-related admissions associated with alcohol has also increased
      significantly (P < 0.001). CONCLUSION: The frequency of assault-related
      admissions to hospital, especially among the Aboriginal population, suggests that
      this major public health issue is escalating.

PMID- 12225277
TI  - Cardiac arrests treated by ambulance paramedics and fire fighters.
AB  - The Emergency Medical Response (EMR) program is a Victorian Government initiative
      in which fire fighters trained in cardiopulmonary resuscitation and equipped with
      automatic external defibrillators are dispatched to suspected cardiac arrests
      simultaneously with ambulance paramedics across metropolitan Melbourne. During
      the first 12 months (February 2000 to February 2001) of the expanded EMR program,
      2942 events involved simultaneous dispatch of ambulance paramedics and fire
      fighters. In 430 events, patients had suffered a cardiac arrest of presumed
      cardiac cause, and resuscitation was attempted by the emergency medical services.
      Fire fighters provided the initial defibrillation to 41 (26.5%) patients
      presenting in ventricular fibrillation. Survival to hospital discharge for
      bystander-witnessed ventricular fibrillation cardiac arrests was 21.8%. The mean
      emergency services (fire and ambulance) response time to cardiac arrest patients
      was 6.03 (SD, 1.65) minutes. The mean time to defibrillation for ventricular
      fibrillation patients was 8.75 (SD, 2.07) minutes.

PMID- 12225278
TI  - Reform of the Australian Health Care Agreements: progress or political ploy?

PMID- 12225279
TI  - Australian Health Care Agreements 2003-2008: a new dawn?

PMID- 12225280
TI  - Adult human neural stem cells for cell-replacement therapies in the central
      nervous system.
AB  - Human neural stem cells (HNSCs) can be isolated from both the developing and
      adult central nervous system (CNS). HNSCs can be successfully grown in culture,
      are self-renewable, and can generate mature neuronal and glial progeny. Embryonic
      HNSCs can be induced to differentiate into specific neuronal phenotypes. HNSCs
      successfully integrate into the host environment after transplantation into the
      developing or adult CNS. HNSCs transplanted into animal models of Parkinson's
      disease and spinal cord injury have induced functional recovery. The risks
      associated with stem cell transplantation trials are difficult to assess, but
      have not become overtly apparent throughout preclinical investigations. Major
      hurdles remain to be overcome before human clinical trials can be embarked upon.

PMID- 12225281
TI  - Humanistic medicine or values-based medicine. what's in a name?
AB  - "Humanistic medicine" is a term compounded, for therapeutic purposes, with the
      good intent of reminding clinicians of their need to be compassionate and
      empathic. Although the expression is arresting, and demands thought, it does not
      go far enough. "Values-based medicine" is a stronger term, reminding clinicians
      of the sustaining values that underpin the whole health endeavour. These values
      include an acceptance of the value of individual human life in quantity and
      quality, and of the importance to both individuals and communities of human
      security and flourishing. Values-based medicine can incorporate all the other
      paradigms of medicine, including scientific and evidence-based medicine, within
      it, because it can include anything that contributes to human security and
      flourishing. If we are to seek a new paradigm for a reconstructed view of
      healthcare, the term "values-based medicine" might have more power and relevance
      than "humanistic medicine".

PMID- 12225282
TI  - Diabetic muscle infarction.

PMID- 12225283
TI  - 11: Antibiotic resistance.
AB  - Antibiotic resistance is a consequence of antibiotic use - we need to use
      antibiotics less and to use them prudently. Plans to combat antibiotic resistance
      were recently proposed by the World Health Organization, a United States
      interagency taskforce and the Australian Joint Expert Technical Advisory
      Committee on Antibiotic Resistance. Prudent antibiotic use includes not using
      antibiotics when benefit is minimal (eg, in many respiratory tract infections),
      using narrow-spectrum antibiotics whenever possible and using optimal dosages and
      regimens. The need for antibiotic therapy can be reduced by preventing infections
      through vaccination, infection control measures and improved sanitation.
      Surveillance of antibiotic resistance is needed to target interventions for
      minimising antibiotic use. More research is needed into new antibiotics and
      regimens and into improving medical devices and protocols to prevent infection.
      Some simple changes to practice could reduce development and spread of antibiotic
      resistance

PMID- 12225284
TI  - Linezolid-induced neuropathy.

PMID- 12225285
TI  - Cervical screening: time to change the policy.

PMID- 12225286
TI  - Screening mammography and mortality.

PMID- 12225287
TI  - Communication loads on clinical staff in the emergency department.

PMID- 12225288
TI  - Parasite elimination programs: home and away.

PMID- 12225289
TI  - Differential targeting of the stress mitogen-activated protein kinases to the c
      Jun dimerization protein 2.
AB  - The mitogen-activated kinases are structurally related proline-directed
      serine/threonine kinases that phosphorylate similar phosphoacceptor sites and
      yet, in vivo, they exhibit stringent substrate specificity. Specific targeting
      domains (kinase docking domains) facilitate kinase-substrate interaction and play
      a major role in substrate specificity determination. The c-Jun N-terminal kinase
      (JNK) consensus docking domain comprises of a KXXK/RXXXXLXL motif located in the
      delta-domain of the c-Jun N-terminal to the phosphoacceptor site. The c-Jun
      dimerization protein 2 is phosphorylated by JNK on Thr-148. Activating
      transcription factor 3 (ATF3) is a basic leucine zipper protein which is highly
      homologous to c-Jun dimerization protein 2 (JDP2), especially within the
      threonine/proline phosphoacceptor site, Thr-148. Nevertheless, ATF3 does not
      serve as a JNK substrate in vitro or in vivo. Using ATF3 and JDP2 protein
      chimaeras, we mapped the JNK-docking domain within JDP2. Although a JNK consensus
      putative docking site is located within the JDP2 leucine zipper motif, this
      domain does not function to recruit JNK to JDP2. A novel putative docking domain
      located C-terminally to the JDP2 phosphoacceptor site was identified. This
      domain, when fused to the ATF3 heterologous phosphoacceptor site, can direct its
      phosphorylation by JNK. In addition, although the novel JNK-docking domain was
      found to be necessary for p38 phosphorylation of JDP2 on Thr-148, it was not
      sufficient to confer JDP2 phosphorylation by the p38 kinase.

PMID- 12225291
TI  - Regulation of intracellular glutathione levels in erythrocytes infected with
      chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum.
AB  - Malaria is one of the most devastating tropical diseases despite the availability
      of numerous drugs acting against the protozoan parasite Plasmodium in its human
      host. However, the development of drug resistance renders most of the existing
      drugs useless. In the malaria parasite the tripeptide glutathione is not only
      involved in maintaining an adequate intracellular redox environment and
      protecting the cell against oxidative stress, but it has also been shown that it
      degrades non-polymerized ferriprotoporphyrin IX (FP IX) and is thus implicated in
      the development of chloroquine resistance. Glutathione levels in Plasmodium 
      infected red blood cells are regulated by glutathione synthesis, glutathione
      reduction and glutathione efflux. Therefore the effects of drugs that interfere
      with these metabolic processes were studied to establish possible differences in
      the regulation of the glutathione metabolism of a chloroquine-sensitive and a
      chloroquine-resistant strain of Plasmodium falciparum. Growth inhibition of P.
      falciparum 3D7 by D,L-buthionine-( S, R )sulphoximine (BSO), an inhibitor of
      gamma-glutamylcysteine synthetase (gamma-GCS), and by Methylene Blue (MB), an
      inhibitor of gluta thione reductase (GR), was significantly more pronounced than
      inhibition of P. falciparum Dd2 growth by these drugs. These results correlate
      with the higher levels of total glutathione in P. falciparum Dd2. Short-term
      incubations of Percoll-enriched trophozoite-infected red blood cells in the
      presence of BSO, MB and N, N (1)-bis(2-chloroethyl)- N -nitrosourea and
      subsequent determinations of gamma-GCS activities, GR activities and glutathione
      disulphide efflux revealed that maintenance of intracellular glutathione in P.
      falciparum Dd2 is mainly dependent on glutathione synthesis whereas in P.
      falciparum 3D7 it is regulated via GR. Generally, P. falciparum Dd2 appears to be
      able to sustain its intracellular glutathione more efficiently than P. falciparum
      3D7. In agreement with these findings is the differential susceptibility to
      oxidative stress of both parasite strains elicited by the glucose/glucose oxidase
      system.

PMID- 12225290
TI  - The role of myosin in vesicle transport during bovine chromaffin cell secretion.
AB  - Bovine adrenomedullary cells in culture have been used to study the role of
      myosin in vesicle transport during exocytosis. Amperometric determination of
      calcium-dependent catecholamine release from individual digitonin-permeabilized
      cells treated with 3 microM wortmannin or 20 mM 2,3-butanedione monoxime (BDM)
      and stimulated by continuous as well as repetitive calcium pulses showed
      alteration of slow phases of secretion when compared with control untreated
      cells. The specificity of these drugs for myosin inhibition was further supported
      by the use of peptide-18, a potent peptide affecting myosin light-chain kinase
      activity. These results were supported also by studying the impact of these
      myosin inhibitors on chromaffin granule mobility using direct visualization by
      dynamic confocal microscopy. Wortmannin and BDM affect drastically vesicle
      transport throughout the cell cytoplasm, including the region beneath the plasma
      membrane. Immunocytochemical studies demonstrate the presence of myosin types II
      and V in the cell periphery. The capability of antibodies to myosin II in
      abrogating the secretory response from populations of digitonin-permeabilized
      cells compared with the modest effect caused by anti-myosin V suggests that
      myosin II plays a fundamental role in the active transport of vesicles occurring
      in the sub-plasmalemmal area during chromaffin cell secretory activity.

PMID- 12225293
TI  - Consequenses for HRT following the HERS II and WHI reports: the primum non nocere
      is important, but translation into quo vadis is even more essential.
AB  - In the Nordic countries the prevalence of hormonal replacement therapy (HRT) use
      in women from 50 to 70 years of age is slightly above 30% evaluated by sales
      figures and with some variation between the five countries. The premise for this
      commentary is to discuss the best clinical practice when prescribing HRT to post
      menopausal women following the publication of the most recent evidence from two
      well conducted randomized placebo controlled trials, namely the Heart and
      Estrogen/Progestin Replacement Study II (HERS II) and the Women's Health
      Initiative study (WHI ).

PMID- 12225294
TI  - Ultrasonographic endometrial thickness for diagnosing endometrial pathology in
      women with postmenopausal bleeding: a meta-analysis.
AB  - Our aim was to determine the diagnostic accuracy of endometrial thickness
      measurement by pelvic ultrasonography for predicting endometrial carcinoma and
      disease (hyperplasia and/or carcinoma) during an investigation of postmenopausal
      bleeding. We performed a systematic quantitative review of the available
      published literature, which consisted of online searching the MEDLINE and EMBASE
      databases (1966-2000) coupled with scanning of bibliography of known primary and
      review articles. The selection of studies, assessment of study quality, and
      extraction of data were performed in duplicate under masked conditions. Included
      in the analyses were 57 studies with 9031 patients. Accuracy data were summarized
      using likelihood ratios for various cut-off levels of abnormal endometrial
      thickness. The commonest cut-offs were 4 mm (9 studies) and 5 mm (21 studies),
      measuring both endometrial layers. None of the nine studies using the < or = 4 mm
      cut-off level were of good quality. Only four studies (out of the 21) used the <
      or = 5 mm cut-off level, which employed the best-quality criteria. Using the
      pooled estimates from these four studies only, a positive test result raised the
      probability of carcinoma from 14.0% (95% CI 13.3-14.7) to 31.3% (95% CI 26.1
      36.3), while a negative test reduced it to 2.5% (95% CI 0.9-6.4). In conclusion,
      ultrasound measurement of endometrial thickness alone, using the best-quality
      studies cannot be used to accurately rule. However, a negative result at < or = 5
      mm cut-off level measuring both endometrial layers in the presence of endometrial
      pathology rules out endometrial pathology with good certainty.

PMID- 12225292
TI  - A prothrombin activator from Bothrops erythromelas (jararaca-da-seca) snake
      venom: characterization and molecular cloning.
AB  - A novel prothrombin activator enzyme, which we have named 'berythractivase', was
      isolated from Bothrops erythromelas (jararaca-da-seca) snake venom.
      Berythractivase was purified by a single cation-exchange-chromatography step on a
      Resource S (Amersham Biosciences) column. The overall purification (31-fold)
      indicates that berythractivase comprises about 5% of the crude venom. It is a
      single-chain protein with a molecular mass of 78 kDa. SDS/PAGE of prothrombin
      after activation by berythractivase showed fragment patterns similar to those
      generated by group A prothrombin activators, which convert prothrombin into
      meizothrombin, independent of the prothrombinase complex. Chelating agents, such
      as EDTA and o -phenanthroline, rapidly inhibited the enzymic activity of
      berythractivase, like a typical metalloproteinase. Human fibrinogen A alpha-chain
      was slowly digested only after longer incubation with berythractivase, and no
      effect on the beta- or gamma-chains was observed. Berythractivase was also
      capable of triggering endothelial proinflammatory and procoagulant cell
      responses. von Willebrand factor was released, and the surface expression of both
      intracellular adhesion molecule-1 and E-selectin was up-regulated by
      berythractivase in cultured human umbilical-vein endothelial cells. The complete
      berythractivase cDNA was cloned from a B. erythromelas venom-gland cDNA library.
      The cDNA sequence possesses 2330 bp and encodes a preproprotein with significant
      sequence similarity to many other mature metalloproteinases reported from snake
      venoms. Berythractivase contains metalloproteinase, desintegrin-like and cysteine
      rich domains. However, berythractivase did not elicit any haemorrhagic response.
      These results show that, although the primary structure of berythractivase is
      related to that of snake-venom haemorrhagic metalloproteinases and functionally
      similar to group A prothrombin activators, it is a prothrombin activator devoid
      of haemorrhagic activity. This is a feature not observed for most of the snake
      venom metalloproteinases, including the group A prothrombin activators.

PMID- 12225295
TI  - Expression of the vascular endothelial growth factors B and C and their receptors
      in human endometrium during the menstrual cycle.
AB  - BACKGROUND: Endometrial angiogenesis is important for bleeding control and
      fertility, and is believed to be regulated by angiogenic growth factors under the
      influence of ovarian steroids. OBJECTIVE: To document the pattern of expression
      of the two angiogenic growth factors, vascular endothelial growth factor (VEGF)-B
      and VEGF-C, and of their receptors, VEGFR-1, VEGFR-2, and VEGFR-3, in order to
      investigate their possible role in the regulation of angiogenesis in normal
      cycling human endometrium. MATERIAL AND METHODS: Cryosections of endometrial
      biopsy specimens obtained from 17 healthy women before laparoscopic sterilization
      were examined by immunohistochemistry. RESULTS: Vascular endothelial growth
      factor and VEGF-C and their receptors were all expressed in and around
      endometrial blood vessels, with no obvious menstrual cycle-dependent changes in
      expression except for VEGFR-2, which showed stronger expression during the early
      secretary phase. Stromal blood vessel density did not change significantly during
      the menstrual cycle. CONCLUSION: The presence and pattern of expression of these
      angiogenic growth factors and their receptors suggest that they participate in
      the regulation of normal endometrial angiogenesis.

PMID- 12225296
TI  - Effect of magnesium sulfate, isradipine, and ritodrine on contractions of
      myometrium: pregnant human and rat.
AB  - BACKGROUND: Magnesium sulfate, isradipine, and ritodrine are smooth muscle
      relaxants used for treating preterm labor. The aim of this study is to
      investigate the action profile of these drugs on the amplitude and frequency of
      spontaneous contractions of isolated myometrial strips of pregnant human and rat.
      MATERIAL AND METHODS: Isolated myometrial strips were obtained from humans
      undergoing elective cesarean section at term pregnancy and Wistar albino rats on
      gestational days 19-21. These strips were mounted in organ baths for recording of
      isometric tensions. The effect of magnesium sulfate, isradipine, and ritodrine on
      the amplitude and frequency of spontaneous contractions was compared with the
      anova test. RESULTS: Ritodrine (10-8-10-5 M) concentration-dependently inhibited
      the frequency and amplitude of spontaneous contractions of myometrial strips. At
      10-4 M, tachyphylaxis of ritodrine occurred and contractions started again.
      Magnesium sulfate (10-7-10-4 M) inhibited the frequency but did not change the
      amplitude of the spontaneous contractions. Isradipine (10-7-10-4 M) had a
      concentration-related inhibitor effect on both the frequency and amplitude of the
      spontaneous contractions. The effects of magnesium sulfate, isradipine, and
      ritodrine were considerably similar in myometrium strips obtained from pregnant
      rats and humans. CONCLUSIONS: Because of tachyphylaxis, the effectiveness of
      ritodrine is limited for inhibition of myometrial contractions. Magnesium sulfate
      reduced the frequency of spontaneous contractions without affecting the
      amplitude. Isradipine may be an interesting therapeutic alternative in situations
      where inhibition of uterine activity is desirable.

PMID- 12225297
TI  - Validity of a rheumatic disease diagnosis in the Medical Birth Registry of
      Norway.
AB  - BACKGROUND: In our population-based study of pregnancy outcome in women with
      rheumatic disease we based our assessment on the Medical Birth Registry of Norway
      (MBRN). We evaluated the MBRN as a source of data for such epidemiologic research
      by assessing the validity of a diagnosis of rheumatic disease in the MBRN against
      a gold standard. The validity may also be interpreted as a quality indicator,
      reflecting an obstetrician's attention to rheumatic diseases in pregnancy.
      METHODS: Using the mother's national identification number the MBRN was linked
      with local hospital databases (gold standard), which contained data of mothers
      with rheumatic disease. The sensitivity of the MBRN was calculated as the
      proportion of all cases registered locally with a diagnosis of rheumatic disease
      notified to the MBRN. The correctness of type differentiation was calculated as
      the proportion of all cases notified to the MBRN that was correct with respect to
      the type of rheumatic disease. RESULTS: Among 169 mothers, 149 had a diagnosis in
      the MBRN, representing a sensitivity of 88.2%. Altogether, 97.3% of the diagnoses
      (145/149) were correct with respect to the type of rheumatic disease. CONCLUSION:
      Taken in to consideration the limitations of the study, namely the small numbers
      studied, we assume a rather high validity of rheumatic disease diagnoses in the
      MBRN, probably reflecting a high level of attention in the obstetric care for
      these patients.

PMID- 12225298
TI  - Insulin dose during glucocorticoid treatment for fetal lung maturation in
      diabetic pregnancy: test of an algorithm [correction of analgoritm].
AB  - OBJECTIVE: Poor glycemic control is often a serious clinical problem during
      glucocorticoid treatment for fetal lung maturation in pregnant women with
      diabetes. An algorithm for improved subcutaneous insulin treatment during
      glucocorticoid treatment in insulin-dependent diabetic women was developed and
      tested. STUDY DESIGN: The sample, divided into two cohorts, consisted of all
      insulin-dependent diabetic women (n=16) receiving glucocorticoid treatment
      (betamethasone 12 mg i.m., repeated after 24 h) from 1996 to 1999. In the first
      cohort the increments of insulin dose were based on the level of blood glucose
      obtained. Based on the first cohort an algorithm to determine increments of
      insulin dose was developed. In the second cohort (n = 8) the insulin dose was
      increased by up to 40%, according to the algorithm, starting immediately after
      glucocorticoid treatment; prior to a detectable increase in blood glucose.
      RESULTS: After betamethasone, the daily insulin dose for the following 5 days was
      increased by 6, 38, 36, 27 and 17% in the first cohort vs. 27, 45, 40, 31 and 11%
      in the second cohort. The algorithm was used in the second cohort. The median
      blood glucose was 6.7, 14.3, 12.3, 7.7 and 7.7 vs. 7.7, 8.2, 9.6, 7.0 and 7.4
      mmol/l (p<0.05 for day 2 and 3) in the two cohorts, respectively. None developed
      ketoacidosis or severe hypoglycemia. CONCLUSION: An algorithm with an increasing
      insulin dose of up to 40% shortly after glucocorticoid treatment for fetal lung
      maturation in diabetic women prevents severe dysregulation of metabolic control.

PMID- 12225299
TI  - Antithrombin III activity and platelet count are more likely to decrease in twin
      pregnancies than in singleton pregnancies.
AB  - BACKGROUND: It is not known whether antithrombin III activity and platelet count
      are more likely to decrease in women with twin pregnancies than singleton
      pregnancies. METHODS: We enrolled 56 consecutive women with twin pregnancies and
      692 consecutive women with singleton pregnancies. Antithrombin III activity and
      platelet count were determined at 26-31 weeks and again at 32-40 weeks of
      gestation. Thrombin-antithrombin complex, and plasmin-alpha2 plasmin inhibitor
      complex were measured simultaneously in some women. RESULTS: In twin pregnancies,
      both antithrombin III activity (111 +/- 8.2%) and platelet count (244 +/- 60 x
      109/l) at 28.6 +/- 1.0 weeks decreased over time to 91 +/- 12% and 205 +/- 59 x
      109/l, respectively, at 35.2 +/- 1.2 weeks; these decreases were significantly
      greater than in singleton pregnancies. However, a small number of women with
      singleton pregnancies had a significant decrease in antithrombin III activity in
      the absence of preeclampsia. The serum thrombin-antithrombin complex was
      significantly higher in twin pregnancies than in singleton pregnancies (9.7 +/-
      4.2 ng/ml vs. 6.7 +/- 4.4 ng/ml, respectively, p < 0.01), and this increase
      correlated significantly with the decrease in antithrombin III activity in twin
      pregnancies (r = -0.459, p < 0.001). CONCLUSIONS: Antithrombin III activity and
      platelet count show a greater decrease in twin than in singleton pregnancies,
      perhaps due to a greater increase in thrombin generation.

PMID- 12225300
TI  - Adverse obstetric outcome in fetuses that are smaller than expected at second
      trimester routine ultrasound examination.
AB  - BACKGROUND: Adverse obstetric outcome in fetuses that are smaller than expected
      at second trimester routine ultrasound examination. AIM: To assess the obstetric
      outcome when the interval between the estimated date of delivery by last
      menstrual period and the estimated date of delivery by second trimester
      ultrasound exceeds 14 days. MATERIALS AND METHODS: Population-based prospective
      cohort study. Included were all women (n = 16 302) with a singleton pregnancy, in
      one Norwegian county from 1989 to 1999, with a reliable menstrual history and
      whose second trimester ultrasound examination was conclusive with a 35-60-mm
      biparietal diameter. RESULTS: Adverse outcome was defined as preterm birth (< 37
      weeks), perinatal death, low birthweight (< 2500 g) and small-for-gestational age
      (< 2 standard deviation). The risk for perinatal death (odds ratio = 2.3),
      preterm birth (odds ratio = 1.7), low birth weight (odds ratio = 1.5), and small
      for-gestational age (odds ratio = 1.5) was highly significantly increased in
      deliveries where the discrepancy between the two terms was more than 14 days. The
      increased risk is not explained by differences in parity, maternal age, smoking,
      fetal malformations, or use of oral contraceptives before pregnancy. CONCLUSION:
      Fetuses that are smaller than expected at the mid-second trimester ultrasound
      corresponding to a discrepancy of more than 14 days have an increased risk for
      adverse obstetric outcome.

PMID- 12225301
TI  - Amniotic fluid index in low-risk pregnancy as an admission test to the labor
      ward.
AB  - BACKGROUND: Oligohydramnios has been shown to be a predictor of intrapartal fetal
      distress. In a selected group of low-risk pregnancies, however, it has not yet
      been established that oligohydramnios contributes to intrapartal fetal distress.
      METHODS: Ultrasonically estimated four-quadrant amniotic fluid index as a test
      for admission to the labor ward was evaluated as a predictive factor for fetal
      distress during labor in a prospective "blind" study comprising 600 low-risk
      pregnancies. Oligohydramnios was defined as an amniotic fluid index < or = 50 mm.
      The parturients were divided into two groups according to the status of the fetal
      membranes. The amniotic fluid index results were correlated to fetal outcome:
      Apgar score at 1 and 5 min, pH of blood in umbilical artery and vein, operative
      delivery because of fetal distress, cesarean delivery because of fetal distress,
      and number of babies referred to the neonatal intensive care unit. RESULTS: Two
      hundred and sixty-seven women had ruptured membranes. Among these a significant
      increase in operative delivery because of fetal distress was seen in cases of
      oligohydramnios compared with the normal amount of amniotic fluid (odds ratio
      3.86, confidence interval = 1.25-11.9). No significant differences were seen
      regarding other variables of perinatal outcome. The group with intact membranes
      comprised 333 parturients. Among these, no significant differences in perinatal
      outcome could be seen in relationship to the amniotic fluid index, although a 50%
      increase in emergency operations for fetal distress was seen in women with
      oligohydramnios. A significant correlation might have been evident even in that
      group if a larger sample had been studied. CONCLUSION: The results indicate that
      measurement of the amniotic fluid index in low-risk pregnant women admitted for
      labor might identify parturients with an increased risk of intrapartal fetal
      distress.

PMID- 12225302
TI  - Reference range for cervical length in twin pregnancies.
AB  - BACKGROUND: Twin pregnancies are at increased risk of preterm delivery, and
      cervical length measurement by transvaginal ultrasound examination has been shown
      to be an effective method of screening for this complication. The aim of the
      present study is to establish a reference range for cervical length measurement
      throughout gestation in twin pregnancies. METHODS: Prospective study involving
      144 nonselected twin pregnancies that delivered after 34 weeks and underwent
      ultrasound examination every 4 weeks for transvaginal measurement of cervical
      length. Mean cervical length measurements, 95% confidence intervals for the
      estimate and 95% prediction intervals were established throughout gestation by
      linear regression analysis. RESULTS: There was a significant correlation between
      cervical length measurements and gestational age [cervical length (mm) = - 0.758
      * gestation age (weeks) + 56.69, r=- 0.43, p < 0.0001], and mean cervical length
      shortened by approximately 0.8 mm per week, from 47 mm at 13 weeks to 32 mm at 32
      weeks. The corresponding lower limits for the 95% prediction intervals were 29
      and 15 mm, respectively. CONCLUSION: Cervical length shortens gradually
      throughout gestation in twin pregnancies.

PMID- 12225303
TI  - Arterial and ductus venosus Doppler in fetuses with absent or reverse end
      diastolic flow in the umbilical artery: correlation with short-term perinatal
      outcome.
AB  - BACKGROUND: High perinatal morbidity and mortality rates have been reported in
      association with absent or reverse end-diastolic flow velocities in the umbilical
      artery. Doppler of fetal venous blood flow might be a helpful instrument for
      predicting fetal outcome. However, clinical data addressing this issue are rare.
      Thus, the aim of this study was to evaluate arterial and ductus venosus blood
      flow velocities as a predictor of short-term outcome in fetuses with umbilical
      absent or reverse end-diastolic flow velocities. METHODS: Thirty-five high-risk
      single pregnancies complicated by umbilical absent or reverse end-diastolic flow
      velocities were monitored by serial measurement of the pulsatility index of the
      umbilical artery, middle cerebral artery, and ductus venosus waveforms over a
      period of 1-75 days. RESULTS: The mean observation period between first detection
      of an umbilical absent or reverse end-diastolic flow velocity and delivery was
      8.9 days. A significant correlation was found between parameters of short-term
      perinatal outcome (art. pH, art. base excess, development of intraventricular
      hemorrhage, mortality) and end-diastolic flow velocity waveform or pulsatility
      index of the ductus venosus waveform, but not with arterial Doppler parameters.
      Gestational age proved to be the best predictor for duration of assisted
      ventilation and development of respiratory distress syndrome. CONCLUSIONS: Our
      results indicate that in high-risk pregnancies with umbilical absent or reverse
      end-diastolic flow velocities, determination of blood flow velocities in the
      ductus venosus is a useful additional parameter for prediction of fetal outcome
      and for timing delivery.

PMID- 12225304
TI  - Induction to delivery time interval in patients with and without preeclampsia: a
      retrospective analysis.
AB  - BACKGROUND: Anecdotally, it is suggested that patients with preeclampsia have a
      shorter induction to delivery interval than patients without preeclampsia,
      despite there being no good objective evidence. METHODS: A retrospective analysis
      of 136 primiparous, singleton, cephalic, nonassisted vaginal deliveries between
      January 1997 and January 2000. Sixty-eight women had induction of labor for
      preeclampsia and 68 women without preeclampsia had induction of labor for other
      reasons. The two groups were already case-matched for maternal and gestational
      age. The following details were recorded from the case notes: maternal age,
      gestation at delivery, initial Bishop score, total dose of prostaglandin
      administered, induction to delivery interval, duration of second-stage labor,
      birthweight, and the percentage of Apgar scores < 7 at 5 min. Statistical
      analysis was carried out with a Mann-Whitney U-test, with the aid of SPSS version
      9, Microsoft Windows RESULTS: The women with preeclampsia had a statistically
      significant longer induction to delivery interval than those without
      preeclampsia. The mean induction to delivery interval of women with and without
      preeclampsia was 1049.5 min and 762.5 min, respectively (p < 0.001) CONCLUSION:
      Women with preeclampsia had a longer induction to delivery interval than patients
      without preeclampsia. This fact must be considered when deciding upon the mode of
      delivery in preeclamptic patients.

PMID- 12225305
TI  - Initiation of lactation in women after preterm delivery.
AB  - BACKGROUND: Lactogenesis II describes the onset of copious milk secretion, and
      the success of lactogenesis II has been determined in women by measuring the
      changes in the composition of mammary secretion in the immediate postpartum
      period. AIM AND METHODS: Therefore, the aim of this study was to determine the
      success of lactogenesis II at day 5 postpartum in women expressing milk for their
      preterm infants (n = 22) by measuring the lactogenesis II markers (milk citrate,
      lactose, sodium and total protein) and comparing them with women breastfeeding
      full-term infants (n = 16). RESULTS: There were no significant differences
      between the means (+/- SD) of the lactogenesis II markers for preterm (4.3 +/-
      0.7 mM; 147 +/- 10 mM; 12 +/- 6 mM; 14.0 +/- 1.5 g/l, respectively) and term (3.4
      +/- 1.4 mM; 126 +/- 17 mM; 30 +/- 13 mM; 15.3 +/- 2.5 g/l, respectively) women.
      However, variation about the mean was greater in preterm women (coefficient of
      variation for citrate, 40%; lactose, 14%; sodium, 42%; and total protein, 17%)
      compared with term women (17%, 7%, 33%, and 10%, respectively). All lactogenesis
      II markers were within 3 SD from the means for the term women and thus these
      women were considered to have successfully initiated their lactation. Only 18% of
      preterm women had all four lactogenesis II markers within 3 SD from the mean for
      term women. The remaining 82% of preterm women had at least one of the markers of
      lactogenesis II at pre-initiation concentrations (36% had 1 marker, 32% had 2
      markers, and 14% had 3 markers). Furthermore, these women had significantly lower
      24-hr milk production than those preterm women that had all four markers within 3
      SD from the mean of the term women. CONCLUSIONS: It was concluded that 82% of
      preterm women had a compromised initiation of lactation, and this was not uniform
      in all women.

PMID- 12225306
TI  - Hemorrhage risk during operative hysteroscopy.
AB  - BACKGROUND: To evaluate the risk of hemorrhage during hysteroscopic surgery.
      METHODS: Cases of hemorrhage during hysteroscopic surgery were assessed in a
      single center, observational, prospective study conducted from 1990 to 2000,
      including 2116 surgical hysteroscopies. Risk of hemorrhage was evaluated
      according to the hysteroscopic procedure. The management of this complication was
      also noted. RESULTS: Thirteen cases (0.61%) were reported. In six cases,
      hemorrhage stopped spontaneously. For six patients, a Foley (no. 10) probe was
      introduced into the uterine cavity and inflated for 24 h to stop hemorrhage. For
      one patient, immediately from the start of the procedure, the uterine arteries
      were ligatured through the vaginal route in order to stop bleeding. Haemorrhage
      risk was higher during hysteroscopic adhesiolysis compared with endometrial
      ablation (Relative risk [RR] 5.22 (1.26-21.64); p = 0.02), polyp [RR 5.3 (1.04
      27.09); p = 0.04], and fibroid resections [RR 6.55 (1.58-27.17); p = 0.01].
      Haemorrhage risk was however, comparable for endometrial ablation, uterus septa
      section, polyp, and fibroid resections (p = 0.92). CONCLUSIONS: Hemorrhage risk
      is higher during synechiolysis compared with other procedures. An inflated Foley
      probe may be an efficient means of stopping hemorrhage.

PMID- 12225307
TI  - Transvaginal hydrolaparoscopy: a new diagnostic tool in infertility
      investigation.
AB  - BACKGROUND: To establish the value of a new technique called transvaginal
      hydrolaparoscopy for exploration of the tubo-ovarian structures in the management
      of patients with unexplained infertility. METHODS: A total of 120 women with
      primary or secondary infertility, and without obvious pelvic pathology, were
      included in the study. The first 14 patients received general anesthesia and
      underwent transvaginal laparoscopy immediately before standard laparoscopy. The
      remaining 106 patients had transvaginal laparoscopy performed under local
      anesthesia, with standard laparoscopy performed only on those with pathology,
      which required operative intervention. Information on pathology, complications,
      and successful access to the pouch of Douglas were recorded. RESULTS: The
      successful rate of access was 93%. Pathology was found in 29 patients, of whom 15
      required operative laparoscopy. Also, out of 19 patients with adhesions, 11 (58%)
      had normal dye test bilateral, and only two (11%) had bilateral occlusion of the
      tubes. No complications were observed. CONCLUSION: Transvaginal hydrolaparoscopy
      is a safe and well-tolerated method for investigating the tubo-ovarian structures
      in unexplained infertility. It is superior to hysterosalpingography for diagnosis
      of adhesions.

PMID- 12225308
TI  - Reproductive tract infections and the risk of HIV among women in Moshi, Tanzania.
AB  - OBJECTIVES: The objectives of the study were to determine the prevalence of HIV
      and reproductive tract infections (RTIs); to compare the occurrence of RTIs among
      HIV-infected and non-infected women; and to assess the association of HIV with
      RTIs and behavioral factors among women aged 15-49 years. METHODS: A cross
      sectional study was conducted in late 1999 among 382 consenting women attending
      three primary healthcare clinics. They were interviewed and screened for HIV-1
      and RTIs. RESULTS: The prevalence of HIV-1 was 11.5%. Sixty-four percent of the
      women had one ongoing treatable RTI. Endogenous and sexually transmitted RTIs
      were higher in HIV-positive than negative women and 84% of the HIV seropositive
      women were co-infected with one treatable RTI. HIV was significantly associated
      with cervicitis (chlamydial or gonococcal) [OR = 3.2 (CI 1.1-13.2)], HSV-2 [OR =
      2.6 (CI 1.3-5.1)], bacterial vaginosis [OR = 1.9 (CI 1.1-4.1)], genital warts [OR
      = 4.8 (CI 1.1-22.2)], and presence of vaginal discharge [OR = 2.7 (CI 1.3-5.2)].
      Having more than one lifetime sexual partner, a history of infant mortality or a
      partner who had other wives or resided away from home > 6 months, were risk
      factors for HIV infection. CONCLUSION: HIV-1 and RTIs are a major public health
      problem among women in this population. Integration of routine screening and
      treatment of RTIs in the reproductive health clinics will be an important
      strategy to combat HIV in the area. Further, innovative behavior interventions
      targeting both men and women, preferably as couples are needed.

PMID- 12225309
TI  - Ectrodactyly ectodermal dysplasia-clefting syndrome with hematocolpometra
      presenting as acute urinary retention.

PMID- 12225310
TI  - Oligodendroglioma arising within a mature cystic ovarian teratoma: case report
      and review of the literature.

PMID- 12225311
TI  - Low-dose topiramate in adults with treatment-resistant partial-onset seizures.
AB  - OBJECTIVES: Based on dose predictions from animal and human volunteer studies,
      most patients enrolled in initial randomized controlled trials of topiramate as
      adjunctive therapy in adults with partial-onset seizures were randomized to >or=
      600 mg/day topiramate. Subsequent experience suggests that dosage needs were
      overestimated. This double-blind, placebo-controlled study evaluated 200 mg/day
      topiramate in adults with treatment-resistant partial-onset seizures receiving a
      concurrent enzyme-inducing antiepileptic agent (carbamazepine). MATERIALS AND
      METHODS: After a 4-week baseline, 263 adults receiving carbamazepine who had at
      least three partial-onset seizures during the baseline period were randomized to
      placebo or one of two topiramate 200 mg/day treatment arms: topiramate escalated
      weekly 25 mg/day(8-week escalation) or 50 mg/day(4-week escalation). Therapy was
      then maintained for the remainder of the 12-week double-blind study. RESULTS:
      Median percent reduction in seizure frequency from baseline to study end was 44%
      with topiramate and 20% with placebo (P <or= 0.001). A significant therapeutic
      effect was present at 2 weeks with a dose of 100 mg/day. The most common adverse
      events (>or=10% incidence in topiramate-treated patients) were somnolence,
      fatigue, paresthesia, nervousness and anorexia; 8% of topiramate-treated patients
      and 2% of placebo-treated patients discontinued because of adverse events. As a
      result of the low incidence of adverse events, differences between titration
      rates in terms of tolerability were not detected. CONCLUSION: Topiramate 200
      mg/day is an appropriate target dose as adjunctive therapy in adults with
      treatment-resistant partial-onset seizures, even when receiving an enzyme
      inducing agent; 100 mg/day also appears to be effective. A significant
      therapeutic effect may be seen in the second week of treatment with a dose of 100
      mg/day.

PMID- 12225312
TI  - Ictal onset localization of epileptic seizures by magnetoencephalography.
AB  - OBJECTIVES: The aim of this study was to localize the ictal onset zone of focal
      epileptic seizures by magnetoencephalography (MEG) and to compare the results
      with interictal MEG localizations, ictal and interictal electroencephalography
      (EEG) results and magnetic resonance imaging (MRI) in epilepsy surgery
      candidates. MATERIALS AND METHODS: Data of 13 patients with partial seizures
      during MEG recording were analysed. Measurements were performed with a Magnes II
      dual unit system. RESULTS: In six of 13 cases, the ictal onset zone could be
      localized by MEG, with all interictal MEG findings being confirmed by ictal MEG
      results. In four cases, the ictal MEG localization results were corresponding to
      the ictal EEG localization results. In two cases, EEG yielded no comparable
      information. CONCLUSION: Ictal onset localization is feasible with MEG. Both
      interical and ictal MEG contribute valuable information to the presurgical
      assessment of epilepsy patients.

PMID- 12225313
TI  - Prognostic implications of admission inflammatory profile in acute ischemic
      neurological events.
AB  - OBJECTIVE: To reveal the potential prognostic implications of admission
      inflammatory markers in patients with acute ischemic neurological events.
      PATIENTS AND METHODS: Sixty patients with an acute ischemic neurological event
      who were examined within 24 h from the appearance of symptomatology. We
      determined the high-sensitive C-reactive protein (hs-CRP) concentrations,
      erythrocyte sedimentation rate (ESR), fibrinogen concentrations and degree of
      erythrocyte adhesiveness/aggregation. RESULTS: A significant correlation was
      noted between baseline hs-CRP concentrations, ESR as well as
      adhesiveness/aggregation and the outcome of the ischemic neurological event as
      determined by the modified Rankin scale 8-12 months following the insult.
      CONCLUSION: Admission inflammatory markers have long-term prognostic implications
      in patients with acute ischemic neurological events. These findings are relevant
      in view of the new therapeutic interventions now available for reducing the
      inflammatory response.

PMID- 12225314
TI  - Dosing with ropinirole in a clinical setting.
AB  - OBJECTIVES: To determine the optimal dose of ropinirole (ReQuip) for treatment of
      early Parkinson's disease (PD). MATERIALS AND METHODS: Six-month data were
      gathered from three trials of monotherapy in patients with PD. RESULTS: Seventy
      five percent of patients who experienced a therapeutic response did so at <or=
      7.5 mg/day. Patients whose dose was increased by more than four titration levels
      from weeks 4-24 (mean total increase 14.8 mg/day) tended to show greater
      improvements than those whose dose increase was smaller (mean increase 3.4
      mg/day) (17.4% vs 10.8%, respectively). Mean doses continued to increase
      throughout the 3- and 5-year trials (3-year trial at endpoint, 10.4 mg/day; 5
      year trial at 3 years and at endpoint, 14.1 and 14.9 mg/day, respectively).
      CONCLUSION: Although a therapeutic response may be expected at <or= 7.5 mg/day,
      these data suggest a benefit for continued dose titration in most patients with
      early PD. For some patients, the maximum recommended dose (24 mg/day) may be
      necessary.

PMID- 12225315
TI  - Chronic symptoms are common in patients with neuroborreliosis -- a questionnaire
      follow-up study.
AB  - OBJECTIVES: The existence of chronic neuroborreliosis is controversial. The aim
      of our study was to investigate the existence and kind of persistent symptoms in
      patients previously treated because of neurological symptoms as a result of
      neuroborreliosis. MATERIALS AND METHODS: A total of 106 patients with
      neuroborreliosis, according to established criteria, and a control group of 123
      patients with Borrelia induced erythema migrans diagnosed in a general
      practitioner office were studied. A questionnaire was sent to patients and
      controls concerning their health situation. Time from onset of neurological
      symptoms to the questionnaire send out was 32 months (mean) for the patients with
      neuroborreliosis and 33 months (mean) for the controls. RESULTS: Fifty per cent
      of the individuals in the patient group compared with 16% of the individuals in
      the control group showed persistent complaints after their Borrelia infection (P
      < 0.0001). The most significant differences between the groups were the presence
      of neuropsychiatric symptoms such as headache, attention problems, memory
      difficulties and depression. Paresthesia, pain and persistent facial palsy was
      also significantly more common in patients treated because of neuroborreliosis.
      CONCLUSION: Our study shows that persisting neurological symptoms are common
      after a neuroborreliosis infection. The pathological mechanisms that lay behind
      the development of chronic symptoms, however, are still uncertain.

PMID- 12225316
TI  - Enlargements of somatosensory-evoked potentials in progressive supranuclear
      palsy.
AB  - OBJECTIVE: To evaluate the usefulness of the somatosensory-evoked potential (SEP)
      in differentiating progressive supranuclear palsy (PSP) from other movement
      disorders. MATERIALS AND METHODS: The median nerve SEPs were studied in patients
      with PSP, Parkinson's disease and essential tremor, and in healthy controls.
      RESULTS: The amplitudes of the median nerve SEPs were enlarged only in patients
      with PSP. In four of the 10 patients with PSP, giant SEPs were elicited either
      unilaterally or bilaterally. CONCLUSIONS: The enlargement of the SEP in PSP may
      be useful for early differentiation of PSP, and this enlargement suggest a
      disease-specific dysfunction in the sensory processing mechanism of PSP which
      distinguishes it from other movement disorders.

PMID- 12225317
TI  - Ambulatory blood pressure monitoring in patients with spinocerebellar
      degeneration.
AB  - OBJECTIVES: The aim of this study was to demonstrate circadian blood pressure
      trends and to evaluate autonomic function in patients with spinocerebellar
      degeneration (SCD). MATERIALS AND METHODS: We performed 24-h ambulatory blood
      pressure monitoring (ABPM) on 10 patients from seven Japanese families with
      spinocerebellar ataxia type 6 (SCA6), 10 patients with idiopathic cerebellar
      ataxia (ICA), eight patients with multiple system atrophy (MSA) suffering from
      cerebellar MSA (MSA-C), and 12 age- and gender-matched normal subjects. We also
      evaluated autonomic function in these patients. RESULTS: Three SCA6 patients
      (30%), six ICA patients (60%), eight MSA-C patients (100%) and four normal
      subjects (33%) were non-dippers. The nocturnal reduction rate of blood pressure
      in MSA patients was significantly less than those in normal subjects, SCA6
      patients and ICA patients. There were no abnormal findings in any patient with
      SCA6 in autonomic function tests. All dipper patients exhibited normal findings
      on autonomic function tests. This is the first report of ABPM in patients with
      SCD. CONCLUSIONS: Blunted reduction of nocturnal blood pressure may be associated
      with autonomic dysfunction in patients with SCD.

PMID- 12225318
TI  - Muscle force, motor nerve conduction velocity and compound muscle action
      potentials after parathyroidectomy for secondary hyperparathyroidism.
AB  - OBJECTIVE: We studied the motor nerve conduction velocity (MNCV) and the
      amplitude of compound muscle action potentials (CMAP) in patients with
      symptomatic secondary hyperparathyroidism at preoperative and 3 months post
      operative period, to find the factors affecting muscle force after
      parathyroidectomy. METHODS: Twenty-six patients with symptomatic secondary
      hyperparathyroidism with levels of intact parathyroid hormone (iPTH) over 6.8
      pmol/l who underwent total parathyroidectomy and autotransplantation of 60 mg of
      tissue were included in this research. Extension force of the quadriceps muscle
      was measured at 60 degrees of right knee flexion and expressed as Newtons (N) in
      peak force and average force. Nerve conduction studies of four limbs were checked
      and the MNCV and CMAP of right femoral and tibial nerves were analyzed and
      correlated with the muscle force. RESULTS: Three months after operation, the peak
      force increased from 272 +/-108 to 315 +/- 123 N (P=0.015) and the average force
      from 215 +/- 94 to 253 +/- 103 N (P=0.006). MNCV and latencies of femoral and
      tibial nerves did not show definite change, but the amplitude of CMAP increased
      significantly from 7.1 +/- 4.1 to 10.7 +/- 3.2 mV (P=0.005) at femoral
      stimulation and from 9.8 +/- 4.6 to 11.7 +/- 4.3 (P=0.007) and 13.2 +/- 5.9 to
      14.9 +/- 6.0 (P=0.011) at proximal and distal tibial stimulation. CONCLUSION: The
      improvement of muscle force after surgery was found to be parallel to the
      increment of the amplitude of CMAP but not to nerve conduction velocity or
      latency. We propose that the weakness of the patients with secondary
      hyperparathyroidism is probably related to alteration of muscle fiber
      contraction.

PMID- 12225319
TI  - Hereditary spastic paraplegia with thin corpus callosum and cataract: a clinical
      description of two siblings.
AB  - We report two siblings with autosomal recessive hereditary spastic paraplegia and
      thin corpus callosum. These patients had a similar history of progressive spastic
      gait, followed by mental impairment in the second decade. In addition to
      rigospasticity, ataxia, and foot deformity, both patients had congenital cataract
      on ophthalmologic examination. The association of cataract and thin corpus
      callosum suggests a distinct genetic disorder involving these structures in
      complicated spastic paraplegia.

PMID- 12225320
TI  - Secretion of natriuretic peptides caused by an epileptic attack.
AB  - OBJECTIVE: To describe clinical features of a patient with secretions of atrial
      natriuretic peptide (ANP) and brain natriuretic peptide (BNP) during an epileptic
      attack. PATIENT: A 65-year-old woman experienced frequent bouts of polyuria,
      pyrexia and general fatigue after several years of a cerebral contusion involving
      the left fronto-temporal lobe caused by a traffic accident. Her urine output and
      urinary sodium excretion increased, and plasma ANP and BNP concentrations were
      markedly high during each attack. Electroencephalography (EEG) showed serial
      seizure discharge in the left anterior temporal region during the attacks,
      indicative of epileptic focus. CONCLUSION: ANP and BNP secretions probably were
      triggered by epileptic stimulation on the diencephalon beyond the focus.

PMID- 12225321
TI  - Atrio-ventricular block: a possible explanation of sudden unexpected death in
      epilepsy.
AB  - INTRODUCTION: This is the third case report describing the occurrence of total
      atrio-ventricular (AV)-block as a life threatening cardiac arrhythmia
      complicating epileptic seizures. CASE REPORT: A 56-year-old right-handed man was
      admitted to our hospital for surgical assessment of his medically intractable
      epilepsy. During the hospitalization he was enrolled in a study investigating
      cardiac complication of epileptic seizures as the possible cause of sudden
      unexplained death among epileptics. DISCUSSION: To the best of our knowledge, we
      are the first to employ simultaneous video-electroencephalogram-, Holter- and
      pulse oximetry-recordings of our patients in the description of this
      complication. These recordings allowed us to discuss the evidence and
      consequences of this particular cardiac abnormality as an explanation of sudden
      unexplained death in epileptic seizures, especially those of temporal origin.

PMID- 12225322
TI  - Asymmetric pharyngeal-cervical-brachial weakness associated with anti-GT1a IgG
      antibody.
AB  - We report a case of markedly asymmetric pharyngeal-cervical-brachial weakness.
      Acute progression of symptoms, albuminocytologic dissociation in cerebrospinal
      fluid, electrophysiologic evidence of demyelination and elevation of IgG anti-GT1
      a antibody titer paralleled the clinical course, support the diagnosis of
      Guillain-Barre syndrome. Guillain-Barre syndrome should be considered in the
      differential diagnosis of cranial neuropathy, even in cases where there is marked
      asymmetry.

PMID- 12225323
TI  - Visual recovery in a man with the rare combination of mtDNA 11778 LHON mutation
      and a MS-like disease after mitoxantrone therapy.
AB  - We describe a young man with prognostic unfavourable homoplasmatic mitochondrial
      DNA(mt DNA) 11778 Leber's hereditary optic neuropathy (LHON) point mutation and
      confirmed multiple sclerosis (MS). This combination of LHON and MS-like disease
      is rare in both sexes, and in men has been described in only a few case reports.
      In a 4-year follow-up during immunosuppressive therapy with mitoxantrone, we
      found a remarkable time delayed visual recovery 12 months after acute onset of
      rapid sequential bilateral subtotal visual loss followed by episodes of isolated
      acute demyelinative optic neuropathy. Visual recovery to such extent after this
      latency is uncommon in both mtDNA 11778 LHON mutation and optic neuritis (ON) in
      MS. Relapses in visual deterioration must be considered as extremely rare in
      LHON. This case might support the hypothesis of an immunological pathogenetic
      factor in combined LHON and MS, and possibly in LHON alone. We suggest a search
      for the LHON mutation in MS patients with predominant visual impairment,
      independent of patients' gender.

PMID- 12225325
TI  - Regulatory elements of hepatitis B virus transcription.
AB  - The precise modulation of hepatitis B virus (HBV) gene expression is essential
      for replication of the virus. HBV sequences are transcribed under the control of
      the preC/pregenomic, S1, S2 and X promoters. With the exception of S1, all the
      HBV promoters lack the orthodox TATA box motifs required for the formation of the
      transcription initiation complex, and as such they represent a unique model of
      transcription initiation elements. The presence of two enhancer sequences and
      negative regulatory elements in the HBV genome further augments the controlled
      synthesis of HBV- RNA. All these transcription cis-elements are embedded within
      protein coding regions of the genome. This feature demonstrates the remarkable
      ability of the virus to maximize the function of its small genome. HBV
      transcription control elements also display a preference for liver-specific or
      liver-enriched trans-factors, which contributes to the liver tropism of the
      virus. This review outlines the major HBV transcription regulatory elements and
      highlights the reliance of accurate HBV gene modulation on the complex interplay
      between several trans-acting factors and their corresponding cis- motifs in the
      viral genome.

PMID- 12225326
TI  - First-phase parameters in hepatitis C viral kinetics.

PMID- 12225327
TI  - Induction therapy with consensus interferon (CIFN) does not improve sustained
      virologic response in chronic hepatitis C.
AB  - In patients infected with hepatitis C virus (HCV) genotype 1, sustained viral
      response (SVR) averages 10-40% depending on treatment regime. It has been
      proposed that high dose daily interferon (IFN) therapy early in therapy
      (induction dosing) may enhance SVR. In the present study we examined this issue
      and also assessed whether one could predict SVR and non-SVR, based on viral
      kinetics during the first month of induction therapy. End of treatment response
      and SVR was determined in 173 HCV infected patients who were treated with
      different induction doses of consensus interferon (CIFN) for one month followed
      by 11 months of standard 9 microg of CIFN thrice weekly (TIW). The second phase
      decline slope was calculated by log-linear regression on weekly measurements of
      serum HCV RNA during the first 7-28 days of treatment; rapid viral response (RVR)
      during the first month of induction dosing was defined as a decline of > 0.3 log
      copies/mL/week. Overall, SVR occurred in 11% of genotype 1 infected patients and
      41% of patients with nongenotype 1. High dose induction therapy did not increase
      the rate of SVR, in either genotype 1 or genotype 2/3 infected patients. No
      patient without a RVR during the first month had SVR, while SVR occurred in 55%
      of the patients with RVR. RVR was the best predictor of SVR using multivariate
      analysis. These results indicate that induction dosing with CIFN does not improve
      SVR rates. They also suggest that early viral kinetics during the first month of
      therapy can predict non-SVR and thus save a patient a year long treatment which
      is fraught with side-effects and significant cost.

PMID- 12225328
TI  - First phase viral kinetic parameters as predictors of treatment response and
      their influence on the second phase viral decline.
AB  - It has recently been shown that upon initiation of interferon (IFN) treatment
      there is a biphasic decline in hepatitis C virus (HCV) RNA levels. In preliminary
      results, the rate of second phase viral decline has been shown to be an excellent
      predictor of treatment response. In this analysis, we determined whether the
      first phase viral kinetic parameters affected the rate of second phase viral
      decline. We also assessed whether first phase viral kinetic parameters could be
      used to predict treatment response within 24 h of initiating treatment. This
      study is a retrospective analysis of two completed studies from which detailed
      kinetic data were obtained in patients infected with genotype 1 HCV. In both
      studies, viral levels were measured frequently over the first 24 h, allowing the
      determination of IFNs effectiveness in blocking viral production and the viral
      load at the end of the first phase (v1). The second phase decline slope was
      calculated by log-linear regression on measurements of serum HCV RNA during days
      2, 7 and 14. In study one, sustained viral response (SVR) rates were obtained,
      allowing the determination of the first phase's predictive power for SVR.
      Logistic regression and fisher exact tests were used to analyse data. In study
      one, no patient achieved SVR without an IFN effectiveness greater than 98% and a
      V1 less than 250 000 copies/mL. When V1 and IFN effectiveness were combined to
      predict SVR, a negative predictive value= 100%, positive predictive value=71% and
      accuracy of 95% was obtained after only 24 h of IFN treatment. Both studies
      illustrated strong correlations for both IFN effectiveness and V1 with the rate
      of 2nd phase slope (P < 0.001). V1 also correlated significantly with a
      calculation of infected cell loss (delta), which is a major determinant of the
      second phase viral decline. These results suggest that early viral kinetics may
      predict lack of response after only 24 h of treatment initiation and indicate a
      strong link between the degree of viral load reduction during the first phase,
      and the subsequent 2nd phase decline slope. This might be explained by a viral
      dynamics model assuming a jump-start of the immune response when viral loads are
      reduced below a threshold, subsequently giving rise to a faster 2nd phase decline
      slope.

PMID- 12225329
TI  - A multicentre, randomized study to evaluate the safety and efficacy of histamine
      dihydrochloride and interferon-alpha-2b for the treatment of chronic hepatitis C.
AB  - Interferon- (IFN-)alpha is currently the standard of care treatment for patients
      with chronic hepatitis C virus (HCV) infection. A significant part of the benefit
      of IFN-alpha in chronic hepatitis C is believed to be related to the activation
      of lymphocytes such as T cells and natural killer (NK) cells, which participate
      in the elimination of infected cells. Histamine dihydrochloride (HDC) has been
      shown to potentiate the IFN-alpha-induced activation of T cells and NK cells by a
      mechanism that involves the protection of these lymphocytes against oxygen
      radical-induced functional inhibition and apoptosis. This study was designed to
      examine the efficacy and safety of HDC in combination with IFN-alpha-2b in
      treatment-naive patients with chronic HCV infection. All patients received IFN
      alpha-2b, 3 MIU, three times weekly via subcutaneous injection, and were
      randomized to one of four HDC regimens (1 mg of either: once a day, three times a
      week; once a day, five times a week; twice a day, three times a week or; twice a
      day, five times a week). The doses of HDC in combination with IFN-alpha-2b
      resulted in sustained viral response rates ranging from 31% to 38%. Sustained
      biochemical response rates ranged from 28% to 41% across the four treatment
      groups. Patients infected with HCV genotype 1, and those with high baseline viral
      levels, which are characteristics associated with poor prognosis, had sustained
      virologic response rates ranging from 18% to 42% and 15% to 39%, respectively.
      Combination treatment was generally well tolerated. We propose that the potential
      benefit of HDC + IFN therapy for chronic HCV infection should be the focus of
      further investigation.

PMID- 12225330
TI  - Early viral clearance and sustained response in chronic hepatitis C: a controlled
      trial of interferon and ribavirin after high-dose interferon induction.
AB  - High-dose induction with alpha-interferon induces early viral clearance of
      hepatitis C and combined with ribavirin enhances sustained response. We assess
      whether adding ribavirin after viral clearance obtained by alpha-interferon
      induction increased the rate of viral eradication.Forty-one naive patients with
      chronic hepatitis C were randomised to receive, after 4 weeks of 10 mU daily of
      alpha-interferon (induction), 3 mU daily for 22 weeks and 3 mU thrice weekly for
      26 weeks of either interferon alone (monotherapy) or interferon plus 1000-1200 mg
      daily of ribavirin (combination therapy). At the end of the induction phase, 23
      (56%) subjects had cleared HCV-RNA. During therapy, breakthrough was observed in
      four patients on monotherapy, but never in patients on combination therapy. The
      rate of clearance of HCV-RNA was different between monotherapy and combination
      therapy at the end of treatment (40% vs. 76.1%, P=0.02) and at the end of follow
      up (5% vs. 57.1%, P=0.001). Twelve of the 23 patients who cleared HCV-RNA during
      induction, but only one of the 18 still HCV-RNA-positive after 4 weeks of
      therapy, had a sustained response (52.2% vs. 5.6%, P=0.001). Clearance of HCV-RNA
      at 1 week had a high positive predictive value for sustained response in
      combination therapy (PPV=0.75), but not in monotherapy (PPV=0.33). Induction with
      high daily doses of alpha-interferon obtains suppression of hepatitis C in more
      than half of patients, but ribavirin is needed to maintain a sustained response.
      The rate of sustained response is a function of the time to HCV-RNA clearance. In
      patients not responding to induction therapy addition of ribavirin does not
      obtain a sustained virological response.

PMID- 12225331
TI  - Is investigation of hepatitis C virus NS5A gene heterogeneity a tool for
      predicting long-lasting response to interferon therapy in patients with HCV-1b
      chronic hepatitis?
AB  - Nonstructural protein 5A (NS5A) of the hepatitis C virus (HCV) may repress the
      interferon (IFN)-induced protein kinase R (PKR). High variability of different
      regions in the carboxy-terminal half of NS5A implicated in the interaction with
      PKR (particularly the interferon sensitivity determining region (ISDR)) may be a
      predictor of response to IFN in patients infected with genotype 1b of HCV. We
      examined pretreatment serum samples from 17 HCV-1b infected patients included in
      the same schedule of IFN therapy. Seven patients were a rare series of sustained
      responders (SR) with a post-treatment follow-up of 5-7 years, while ten were
      nonresponders (NR). The carboxy-terminal half of the NS5A gene was amplified and
      directly sequenced in all 17 cases. In addition, the entire NS5A gene and the
      part of the HCV E2 gene coding for the hypervariable region 1 (HVR1) were
      amplified, cloned and sequenced in six cases (three NR and three SR). No
      difference in number and distribution of amino acid mutations was observed
      between isolates from SR and NR in any portion of the protein, including the ISDR
      region. Analysis of full length NS5A confirmed no difference between the two
      groups. The NS5A gene sequence was different among the six cases cloned although
      it appeared to be conserved in each individual patient independently of the
      quasispecies complexity evaluated through HVR1 examination. These data indicate
      that pretreatment analysis of theNS5A genomic variability has no value in
      predicting long-lasting response to IFN therapy in HCV-1b-infected patients, and
      that the HCV NS5A gene has high quasispecies homology.

PMID- 12225332
TI  - Interferon retreatment reduces or delays the incidence of hepatocellular
      carcinoma in patients with chronic hepatitis C.
AB  - Inhibition of hepatocarcinogenesis is a crucial issue in treating chronic
      hepatitis C patients, especially those who do not respond completely to
      interferon therapy. Interferon has been reported to reduce the incidence of
      hepatocellular carcinoma (HCC) not only in sustained virological responders but
      also in transient biochemical responders. However, the incidence of HCC increases
      in 5 years or more after interferon therapy in transient biochemical responders.
      The aim of this study is to assess whether interferon retreatment reduces the
      incidence of HCC in chronic hepatitis C patients in whom hepatitis C virus was
      not eradicated during initial interferon therapy. We enrolled 309 patients who
      were not sustained virological responders after initial interferon treatment
      consisting of a total dose of more than 250 megaunits of interferon and were
      followed for more than 2 years after treatment. Ninety-nine patients received
      interferon retreatment and 210 did not. Two courses of interferon therapy were
      administered in 84, three courses in 14 and five courses in one. The incidence of
      HCC was compared between patients with retreatment and those without. In the
      clinical characteristics, retreated patients were younger and followed up for a
      longer time period. The cumulative incidence of HCC was significantly lower in
      retreated patients. In multivariate analysis, patients' age (P=0.018) and the
      number of courses of interferon therapy (P=0.022) were independently associated
      with HCC incidence. These results suggest that interferon retreatment reduces or
      delays the incidence of HCC in chronic hepatitis C patients who did not
      completely respond to initial therapy.

PMID- 12225333
TI  - A single nucleotide polymorphism of the low molecular mass polypeptide 7 gene
      influences the interferon response in patients with chronic hepatitis C.
AB  - Transporter associated with antigen processing (TAP) and low molecular mass
      polypeptides (LMP) play crucial roles in the human leukocyte antigen (HLA) class
      I-restricted antigen presenting systems. This study was performed to elucidate
      whether these antigen-presenting gene polymorphisms could influence the response
      to interferon (IFN) treatment in patients with chronic hepatitis C. Polymorphisms
      of TAP and LMP genes in 175 hepatitis C virus (HCV) patients were determined by
      polymerase chain reaction-restriction fragment length polymorphism. The
      frequencies of these genes were compared between sustained-responders (n=49) and
      nonresponders (n=126), classified by biochemical and virological responses to
      IFN. The distributions of TAP1*, TAP2*, and LMP2 genes between sustained
      responders and nonresponders did not differ. However, LMP7-K gene frequency in
      sustained-responders was higher than that in nonresponders [odds ratio 2.3 (95%
      confidence interval 1.1-4.6); 16%vs 7.9%]. Multivariate analysis revealed that
      LMP7-K and HCV-RNA quantity were independent factors influencing the outcome of
      IFN therapy [4.5 (1.4-14); P=0.011, 0.40 (0.24-0.65); P=0.0003, respectively].
      Furthermore, among patients with a low viral load (< or = 2.0 Meq/mL), the LMP7-K
      positive patients had an even higher ratio of sustained response compared to
      those without LMP7-K [5.9 (1.6-22); 82%vs 44%; P=0.0062]. These findings suggest
      that a single nucleotide polymorphism of LMP7 gene is one of the important host
      factors which independently influence the response to IFN in patients with
      chronic hepatitis C.

PMID- 12225334
TI  - Performance of TRUGENE hepatitis C virus 5' noncoding genotyping kit, a new CLIP
      sequencing-based assay for hepatitis C virus genotype determination.
AB  - The performance of the recently developed, standardized direct sequencing assay
      for hepatitis C virus (HCV) genotyping [TRUGENE HCV 5'-NC (noncoding)] was
      assessed in comparison with the reverse hybridization-based assay INNO-LIPA HCV
      II. Both assays allow HCV genotyping starting from amplification products
      generated by the diagnostic Roche AMPLICOR HCV test. HCV amplicons from 205
      patients were used for this study: 34 were tested prospectively by both methods,
      while 171 had been stored at -20 degrees C for up to 2 years after LiPA
      genotyping. The TRUGENE procedure failed to determine a genotype in six low
      titered samples (3.5 +/- 0.3 log UI/mL vs. 5.2 +/- 0.5 UI/mL for typable
      samples). Type and subtype could be determined by sequencing for 199 samples
      (97%). Among them, five were considered as coinfections by the LiPA method. Three
      LiPA patterns suggesting type 1 and 4 coinfection were not supported by sequence
      analysis while one 1a/2b and one 1a/3a coinfection was backed up by direct
      sequencing. For the remaining 194 samples, type assignment was concordant in 100%
      of the cases. LiPA subtyping was available for 162 samples (83.5%). Sub-typing
      results concurred in 128 cases (79%). NS5B sequencing of discrepant samples
      underscored the limitation of the 5'-noncoding region (NCR) in correct subtype
      assignment. In conclusion, the TRUGENE HCV 5'-NC genotyping kit appeared to be a
      specific and reliable method that can be used in the current indication of HCV
      genotyping.

PMID- 12225335
TI  - Prevalence of hepatitis C virus infection in thalassemia and haemodialysis
      patients in north Iran-Rasht.
AB  - Hepatitis C virus (HCV) seroprevalence and risk factors in north Iran were
      investigated in 105 thalassemia sufferers, 93 haemodialysis patients and 5976
      blood donors by second generation ELISA. Our study showed that haemodialysis
      patients and thalassemia sufferers were at higher risk of having HCV infection;
      the prevalence being 55.9% and 63.8% respectively in comparison to the prevalence
      of blood donors (0.5%). A confirmatory immunoblotting was employed using HCV
      positive cases (54 thalassemia sufferers and 19 blood donors). The result showed
      that 92.6% of samples of the first group and 10.5% of the latter were positive.
      Thus, it can be suggested that ELISA in low-risk cases may produce considerable
      false positives. In HCV-positive patients with thalassemia, the incidence of HCV
      among different age groups and genders was similar but a strong correlation in
      respect to the number of blood transfusion (P=0.008) was observed. In HCV
      positive haemodialysis patients, it was found that there was no correlation with
      liver function tests (alanine aminotransferase and aspartate aminotransferase:
      ALT and AST), but a significant correlation was observed in respect to the
      duration of dialysis(P=0.000) and the number of units transfused (P=0.000).
      Consequently, it still seems blood transfusion is the main factor for increasing
      the incidence of HCV in thalassemia sufferers and haemodialysis patients.

PMID- 12225336
TI  - Effect of administration mode (patient vs physician) and patient's educational
      level on the Turkish version of the International Prostate Symptom Score.
AB  - OBJECTIVES: To compare the effectiveness of the International Prostate Symptom
      Score (IPSS) when administered by the physician to when self-administered by the
      patient. The effect of the patient's educational level on the IPSS was also
      evaluated. METHODS: One hundred and seven previously untreated patients with
      symptomatic benign prostatic hyperplasia (BPH) completed the Turkish version of
      the International Prostate Symptom Score (Turkish I-PSS) and quality of life
      (QOL) questionnaires during a single office visit, first on their own and then
      with an interviewing physician. The patients were categorized into three groups
      according to their educational levels. Paired t-tests were performed to compare
      the total IPSS (tIPSS) and QOL results between the two testing modes. IPSS and
      QOL scores resulting from both modes were compared using a kappa test.
      Differences between the physician-assisted and self-administered scores among the
      different educational groups were further compared using a one-way anova test and
      Post Hoc Multiple Comparisons. To compare the objective effectiveness of tIPSS
      and QOL between the two testing modes, we selected the positive actual state,
      which was maximum urine flow (Qmax) of 15 mL/s or less and constructed receiver
      operating characteristics (ROC) curves for all patients. This estimation was
      constructed for each educational level. RESULTS: There were no statistical
      differences in IPSS and QOL values obtained by the patients or physicians (P >
      0.05). The ROC areas for tIPSS were 0.94 and 0.93, and the ROC areas for QOL
      scores were 0.97 and 0.91 for information obtained by physicians and patients,
      respectively. When IPSS answers and QOL scores were evaluated separately,
      consistency was found across both modes of administration. However, there were
      lower levels of consistency in answers to IPSS questions 2, 5 and 6 (P =
      0.59;0.42; 0.52, respectively). There was no significant difference among the
      aforementioned data in the educational groups. CONCLUSION: Although the total
      IPSS and QOL scores were not affected by the different modes of administration,
      we recommend that the physicians should evaluate answers to questions 2, 5 and 6
      carefully. The present study demonstrates that the educational level did not
      affect the IPSS and QOL when administered either by the physician or the patient.

PMID- 12225337
TI  - Arterial blood gases in extraperitoneal laparoscopic urethrocystopexy.
AB  - BACKGROUND: The aim of this study was to investigate the effects of
      extraperitoneal laparoscopy and carbon dioxide insufflation on hemodynamic
      parameters, arterial blood gases and complications in urethrocystopexy
      operations. METHODS: Twenty-five female patients who underwent extraperitoneal
      laparoscopic mesh urethrocystopexy operation for the correction of urinary
      incontinence were allocated to the study. Hemodynamic parameters were noted and
      blood gas analyzes were performed before the induction of anesthesia, 10 min
      after induction, 5 and 10 min after the beginning of carbon dioxide insufflation,
      at the end of carbon dioxide insufflation and 30 min after exsufflation. RESULTS:
      There was no significant change in mean arterial pressure, peripheral oxygen
      saturation, arterial carbon dioxide pressure, and arterial oxygen saturation
      compared to preinsufflation and preinduction values. End-tidal carbon dioxide
      pressure did not increase above 45 mm/Hg during carbon dioxide insufflation.
      Arterial oxygen saturation and partial oxygen pressure did not decrease.
      Subcutaneous emphysema, pneumothorax, pneumomediastinum and pleural effusion were
      not noted in any patient. CONCLUSION: We conclude that, extraperitoneal
      laparoscopic urethrocystopexy is not associated with hemodynamic and respiratory
      impairment.

PMID- 12225338
TI  - Role of Doppler ultrasound and resistive index in benign prostatic hypertrophy.
AB  - BACKGROUND: The aim of the present study was to assess the resistive index in
      patients with benign prostatic hypertrophy (BPH) and the role of power Doppler
      ultrasonography. METHODS: From April 1996 to December 1997, a total of 214 men
      aged 48-86 years with symptoms of BPH were prospectively enrolled to participate
      in our study. All patients presented to our clinic with lower urinary tract
      symptoms. Transrectal ultrasonography was used to calculate the total prostate
      volume (TPV), transition zone (TZ) volume, transition zone index (TZI = TZ
      volume/TPV) and presumed circle area ratio (PCAR). Power Doppler imaging was used
      to identify the capsular and urethral arteries of the prostate and measure its
      resistive index (RI) value. RESULTS: The RI of capsular arteries significantly
      correlated with theTPV, TZ volume, TZI (r = 0.470; P < 0.0001) and PCAR (r =
      0.334; P < 0.0001). Correlations were found between the RI of capsular arteries
      and the International Prostatic Symptom Score (IPSS) (r = 0.389; P < 0.0001),
      peak flow rate of uroflowmetry (r = -0.393; P < 0.0001). CONCLUSION: We
      demonstrated that an increase of the RI of capsular arteries correlated with
      increases in the TZI and PCAR in BPH. The lower IPSS and peak flow rate
      correlated with the high RI of capsular arteries; however, no correlation between
      the RI of urethral arteries and prostatic parameters was found. The findings
      suggested that the RI of capsular arteries may become the index for measuring
      lower urinary obstruction in the future.

PMID- 12225339
TI  - Prospective randomised trial comparing diethylstilboestrol and flutamide in the
      treatment of hormone relapsed prostate cancer.
AB  - BACKGROUND: Patients with hormone relapsed prostate cancer (HRPC) are often
      treated with flutamide or diethylstilboestrol. However, which of these two
      options is the best treatment for HRPC remains unclear. METHODS: We carried out a
      prospective study to determine and compare the prostate-specific antigen (PSA)
      response and survival in patients with hormone relapsed prostate cancer (HRPC),
      all of whom had previously shown a good response to medical or surgical
      castration. The patients were randomised to treatment with diethylstilboestrol
      (DES) and aspirin, or the antiandrogen flutamide. In addition, quality of life
      was determined by interview and questionnaire. RESULTS: Twenty-eight patients
      were randomised for treatment options. There was a significantly greater fall in
      the PSA (65% vs 35%; P = 0.034) after treatment with diethylstilboestrol compared
      to treatment with flutamide. Median survival also rose after treatment with
      diethylstilboestrol (18 months) compared to flutamide (11 months), but this
      difference did not reach statistical significance. There was no difference in the
      quality of life parameters between the two groups. There were no cardiovascular
      complications in the stilboestrol group. CONCLUSIONS: In HRPC, treatment with
      stilboestrol is associated with a greater PSA fall and an increase in median
      survival when compared to flutamide treatment.

PMID- 12225340
TI  - Impact of arterial occlusion during partial nephrectomy on residual renal
      function: an evaluation with (99m)technetium-dimercaptosuccinic acid
      scintigraphy.
AB  - BACKGROUND: Partial nephrectomy (PNx) has been performed with temporary renal
      arterial occlusion and in situ renal hypothermia (conventional PNx). However, the
      impact of temporary renal arterial occlusion on residual renal function has not
      been well assessed. To address this question, we performed renal scintigraphy
      with (99m)technetium-dimercaptosuccinic acid (DMSA) for the quantitative
      measurement of postoperative residual renal function after conventional PNx and
      partial nephrectomy without arterial occlusion (non-clamping PNx). METHODS:
      Thirty-four patients underwent postoperative DMSA scintigraphy after PNx for
      renal cell carcinoma. No obvious difference in preoperative renal function
      between the diseased kidney and the contralateral kidney was found in any of the
      patients. Of these patients, 24 underwent conventional PNx, and 10 underwent non
      clamping PNx. Residual renal function was evaluated using the relative DMSA
      uptake of the operated kidney. RESULTS: The relative DMSA uptake of the operated
      kidney was 39.9 +/- 7.3% (25.1-58.8) after conventional PNx compared to 34.8 +/-
      8.9% (13.5-45.5) after non-clamping PNx. This difference was not statistically
      significant (P = 0.15). Total ischemic time during conventional PNx had no
      adverse influence on the residual renal function. In the analysis of the other
      determinant factors influencing residual renal function, tumor size was the only
      significant factor that inversely correlated with the relative DMSA uptake.
      CONCLUSION: Our results showed that arterial clamping during PNx has no negative
      impact on the functional residual capacity as long as insitu renal hypothermia is
      adequately performed.

PMID- 12225341
TI  - Ureteroscopy and pneumatic lithotripsy, followed by extracorporeal shock wave
      lithotripsy for the treatment of distal ureteral stones.
AB  - BACKGROUND: We retrospectively reviewed our experience with retrograde
      ureteroscopy (URS) and a pneumatic lithotriptor in 160 patients with distal
      ureteral stones to determine whether prior extracorporeal shock wave lithotripsy
      (ESWL) is a limiting factor in the ureteroscopic procedure. METHODS: From January
      1999 to September 2000, we performed URS and pneumatic lithotripsy in 160
      patients with distal ureteral stones. Seventy-four patients were treated with URS
      primarily (Group 1), while the remaining 86 patients received URS only after ESWL
      had failed (Group 2). For URS and lithotripsy, we used a 9.5 French rigid
      instrument and vibrolith (Elmed, Ankara, Turkey). RESULTS: In Group 1, 73 of 74
      patients (98.6%) were treated successfully by URS alone, as were 81 of 86
      patients (94.4%) in Group 2. Impacted stones were also observed in 17 patients
      from Group 2. In these patients, endoscopic observation revealed edematous
      inflammation above and below the calculus. Ureteral perforation occurred in one
      patient from Group 2, which required surgical repair. There was no significant
      difference in the stone-free rates of the two groups t = 1.4 < 1.96t(
      infinity,0.05). CONCLUSION: Our data demonstrate that when ESWL fails, URS and
      pneumatic lithotripsy is as safe and effective as primary URS. Pneumatic
      lithotripsy also seems to be an effective treatment modality for impacted stones.

PMID- 12225342
TI  - Survey of incidence of urological cancer in South Korea: a 15-year summary.
AB  - BACKGROUND: Although the pattern of cancer incidence in South Korea is not the
      same as that of western countries, urological cancer will become one of the major
      cancers in South Korea in the near future. The pattern of cancer in South Korea
      is becoming steadily similar to that in western countries. It is, therefore,
      important to understand the epidemiological features of cancer. Surveillance of
      cancer incidence and mortality trends provides clues to etiology and helps to
      assess the effects of improved diagnostic, screening and intervention measures.
      METHODS: The subjects of the study were 13,208 patients living in South Korea,
      newly diagnosed with urological cancer during the period of 1985-1999. The data
      were analyzed by age, sex, geography and period of diagnosis (1985-1989; 1990
      1994; 1995-1999). RESULTS: Bladder cancer was the most common urological cancer
      in South Korea (6,867 cases, 52.0%). The incidence of prostate cancer and renal
      cell carcinoma was similar. Male patients outnumbered female patients by a ratio
      of 5.4 : 1. In both sexes, the peak incidence of urological cancer in South Korea
      was noted in the 70+ age group. The geographic distribution of urological cancer
      across seven residential areas was similar. The incidence rate of all urological
      cancer (except urethral and penile cancer) had increased remarkably, especially
      in the last several years. The crude incidence rate of urological cancer among
      Koreans in South Korea was estimated to be 46.55 per 100,000 males, 8.64 per
      100,000 females and 27.67 per 100,000 across both sexes. CONCLUSION: Although
      this survey is not definitive, these data should be useful in showing general
      patterns or changes of incidence of urological cancer in South Korea. The
      elevated incidence of urological cancer noted in our survey also indicates the
      need for continued promotion of urological cancer screening programs. Moreover,
      these results may be useful in indicating directions for future research of
      urological cancer.

PMID- 12225343
TI  - Clinical study of varicocele: statistical analysis and the results of long-term
      follow-up.
AB  - BACKGROUND: The results of clinical examinations of varicocele and the clinical
      outcome of varicocelectomy conducted at Tsukuba University Hospital, Tsukuba
      City, Japan were analyzed. METHODS: The subjects of the present study were sixty
      four infertile male patients with varicocele who visited our hospital from 1991
      to 1999. A physical examination, semen analysis and hormonal evaluation were
      performed for each patient. Patients selected their preferred type of treatment
      (varicocelectomy or conservative treatment) after providing their informed
      consent. RESULTS: The age of the patients was 34.1 +/- 5.1(mean +/- standard
      deviation [s.d.]) years, and the infertile duration was 4.2 +/- 3.0 (mean +/-
      s.d.) years. Fifty-one cases were left-sided; 13 were bilateral. Mean sperm
      density ( yen 106/mL) was 37.2 for Grade I, 21.3 for Grade II and 9.4 for Grade
      III. Sperm density was significantly lower in the higher-graded patients (P =
      0.008). Varicocelectomy was performed in 31 cases; the postoperative/preoperative
      ratio of sperm density was significantly higher in the higher-graded varicocele
      (P = 0.04), and the peak/base ratio of follicle-stimulating hormone (FSH) after
      luteinizing hormone-releasing hormone (LH-RH) stimulation was significantly
      decreased after varicocelectomy (P = 0.007). The pregnancy rate in the partners
      of the varicocelectomized group (60%) was significantly higher than in the
      conservatively treated group (28%) P = 0.04; the mean follow-up duration was 76.2
      months. CONCLUSION: These results show that varicocele should influence
      spermatogenesis, therefore altered spermatogenesis could be effectively treated
      by varicocelectomy, and varicocelectomy should induce a higher probability of
      pregnancy.

PMID- 12225344
TI  - Advanced renal cell carcinoma treated with granulocyte-macrophage colony
      stimulating factor gene therapy: a clinical course of the first Japanese
      experience.
AB  - A phase I study of granulocyte-macrophage colony-stimulating factor (GM-CSF) gene
      transduced tumor vaccine for patients with metastatic renal cell carcinoma (RCC)
      was initiated in 1998, as the first cancer gene therapy in Japan. The study is
      still ongoing, but the first patient is presented here as a case report. The
      patient was a 60-year-old man with Stage IV CRC with multiple lung metastases.
      After surgical resection of the tumor, autologous tumor cells were transduced and
      cultured to produce GM-CSF. The patient received a total of 2.2 x 108 gene
      transduced autologous vaccine cells by subcutaneous injection. During the course
      of vaccination, growth of the largest metastatic mass slowed to some extent;
      however, multiple new lesions developed. About 1 month after the start of low
      dose IL-2 therapy, rapid and remarkable regression in a large lung hilar
      metastatic mass was noticed. The patient died of progressive disease 7 months
      after the start of GM-CSF gene therapy. Careful histological examination by
      autopsy revealed that the responding mass was infiltrated by CD8 positive
      dominant T lymphocytes, and did not exhibit vasculitis or any other changes
      associated with active autoimmune disease.

PMID- 12225345
TI  - Clear cell adenocarcinoma of the urinary bladder inducing acute renal failure.
AB  - We report a case of clear cell adenocarcinoma of the urinary bladder. A 59-year
      old male was referred to our hospital complaining of oliguria, left lower
      abdominal pain and loss of appetite. Ultrasonography revealed bilateral
      hydroureteronephrosis and obstructions at the ureterovesical junction. Magnetic
      resonance imaging demonstrated an invasive irregular tumor located in the
      posterior wall of the urinary bladder and urinary infiltration to the left
      retroperitoneal space. The clinical diagnosis was acute post renal failure due to
      bilateral ureteral obstructions from an invasive bladder tumor. After we
      performed bilateral percutaneous nephrostomy, the patient underwent trans
      urethral biopsy of the bladder tumor, which showed clear cell adenocarcinoma
      extending from the submucosa to the muscular layer, histopathologically. The
      patient died of metastatic disease 8 months after diagnosis. To our knowledge,
      the present case is the 23rd to be reported and demonstrates the shortest
      survival period in the related literature.

PMID- 12225346
TI  - Hyperbaric oxygen therapy for Wegener's granulomatosis with cyclophosphamide
      induced hemorrhagic cystitis.
AB  - A 49-year-old man with Wegener's granulomatosis, who had been treated with
      cyclophosphamide, was admitted to our hospital experiencing gross hematuria. The
      hemorrhage was refractory to multiple conventional treatments. It progressed but
      later was resolved after a course of hyperbaric oxygen therapy.

PMID- 12225348
TI  - The "competent" nurse?

PMID- 12225349
TI  - Congruence or conflict? Challenges in implementing problem-based learning across
      nursing cultures.
AB  - Using the "real-life" situation of delivering an Australian nursing curriculum in
      the Maldives, this paper argues that successful offshore delivery requires far
      more than simply implementing an existing programme on a different site. In
      health education, cultural and contextual circumstances necessitate a critical
      appraisal of the needs of the community and the corresponding attributes of those
      who provide health-care services. This means designing programmes that are
      process oriented and easily adapted to different circumstances, and a commitment
      to maintaining effective communication systems. Although it would seem that
      problem-based learning (PBL) provides the framework for a process-oriented,
      learner-centred curriculum, the paper raises questions about how universally
      relevant the processes embedded in PBL are and describes concerns about the
      intent and purpose of nominating PBL as the preferred instructional strategy for
      cross-cultural projects.

PMID- 12225350
TI  - Sociodemographic factors of families related to postnatal depressive symptoms of
      mothers.
AB  - Postnatal depression in mothers is commonplace as it affects 10-15% of recent
      mothers. Postnatal depression is still an under-diagnosed illness and if
      unidentified, is often left untreated. If left untreated, the depression can have
      an adverse effect not only on the mother, but also on the child's development and
      on the well-being of the whole family. The aim of this survey was to investigate
      the prevalence of postnatal depressive symptoms among Finnish mothers and to
      ascertain the relationship with sociodemographic factors in mothers. A sample of
      1000 families at 2 months postnatal was studied by mailing the Edinburgh
      Postnatal Depression Scale to mothers and a questionnaire on demographic
      characteristics to mothers and fathers. The response rate was 39%. The data were
      examined by means of frequency and percentage distributions. Connections were
      examined using Spearman correlation coefficient and analysis of variance. In all,
      373 mothers and 314 fathers took part in the study. Fifty-five (13%) mothers had
      depressive symptoms. Results show that the number of pregnancies, deliveries or
      children, the mode of delivery or the mother's age were not associated with
      depressive symptoms. However, mothers who had depressive symptoms had fewer years
      of education, shorter duration of breast-feeding and were more dissatisfied with
      family life compared with mothers who exhibited no depressive symptomatology. The
      families of mothers with depressive symptoms had also experienced more problems
      and changes having a profound impact on the family compared with other mothers.

PMID- 12225351
TI  - Relationship between technological influences and caring attributes of Korean
      nurses.
AB  - With many well-prepared nurse academics, a buoyant economy and an advanced health
      care system, it is timely that research addresses some of the features and
      characteristics of Korean nurses and communicates this to the English-speaking
      world. This study focuses on Korean registered nurses and their views of
      themselves as carers in a modern technological environment. By collecting data
      from a sample of 560 registered nurses and using an instrument previously
      administered in an international sample, comparisons to normative data are
      presented and contrasted to recent reports. The instrument uses Likert items to
      measure caring attributes and technological influences. The results show that
      older, more experienced and more qualified Korean nurses tend to report
      significantly higher scores for caring attributes, yet approximately 80% of the
      sample were aged less than 30, 70% were unmarried, 70% had less than 6 years
      experience and 60% were diploma prepared. These results are discussed in the
      light of normative findings from the international study and, in the context of
      this unique homogeneous cultural sample, concern is expressed about the lack of
      senior role models and the apparent drain of senior professionals.

PMID- 12225352
TI  - Evaluation of the extended role of the midwife: the voices of midwives.
AB  - It is not uncommon for midwives in Australian hospitals to order and interpret
      tests and initiate medications. The National Health and Medical Research Council
      only formally acknowledged these practices through recommendations in 1998.
      Successful extension of the midwife's role is assumed to be advantageous to the
      health-care system in its ability to satisfy consumer demand for a less
      medicalized experience and to be cost effective. This paper presents the results
      of the first phase of a three-phase fourth generation evaluation of the extended
      role of the midwife in two acute care settings in the Northern Territory,
      Australia. The results suggest that recognition of the extended role of the
      midwife has the potential to deliver high level continuous midwifery care to
      women, to increase work satisfaction for the midwives and to enhance professional
      autonomy and responsibility in the workplace. However, when compared with their
      counterparts in the United Kingdom and New Zealand, midwives in Australia
      continue to practice with considerable limitations placed on their autonomy.

PMID- 12225353
TI  - Relationship between psychosocial factors and health behaviours for women
      experiencing menopause.
AB  - This study investigated the psychosocial factors related to the health behaviours
      of women at menopause. These health behaviours included choice of intervention by
      women for menopause, particularly consultation of health professionals, use of
      hormone replacement therapy and preferred information sources. A postal
      questionnaire was distributed to a structured random population-based sample of
      400 women in the 45-54 years age group living in south-east Queensland,
      Australia. Explanatory variables were: attitudes to menopause, social
      functioning, mental health, vitality, preventive health practices and lifestyle
      factors. This study found that information, preventive health practices,
      attitudes towards menopause, exercise, number of children living at home, years
      of formal education and working in paid employment, were related to the health
      behaviours of women at menopause. The study concludes that a number of related
      psychosocial factors not associated with hormonal changes may influence the
      health behaviours of menopausal women. It will be important for nurses, other
      health professionals and counsellors to decide how best to respond to these
      findings in consultation with the women affected by their decisions.

PMID- 12225354
TI  - Analysis of sharps injury occurrences at a hospital in Singapore.
AB  - Relatively little attention has been directed to investigating the risks of
      sharps injuries in Singapore. This study examines the epidemiology and causes of
      sharps injuries at a university teaching hospital. The type of instruments, site
      of injuries and personnel involved in each sharps injury were determined
      retrospectively by reviewing the Incident Reports forms and Infection Control
      records between 1997 and 2000. Descriptive information on the forms and records
      were extracted and collected on standard charts. The data were then analysed
      using SPSS Windows software. The rates of sharps injuries were 11.0 per 100
      medical staff and 6.9 per 100 nursing staff. Medical staff yielded highest
      proportion of sharps injuries rendering 33 cases (40.2%), followed by 24 cases
      involving nursing staff (29.3%) and 12 cases of nursing students (14.6%). In
      total, 62.2% of injuries were caused by hollow bore needles (51 cases). Non
      hollow bore needle injuries only accounted for 17.1% of total injuries (14
      cases). Hollow bore needles accounted for the highest proportion of sharps
      injuries in this study, corresponding to findings in other studies. Rates of
      injuries were similar to the rates found at another local hospital. At the
      hospital studied, sharps with safety features had effectively produced no
      reported cases of sharps injuries.

PMID- 12225355
TI  - Nursing discharge summaries of deceased patients with respiratory diseases.
AB  - To explore how nurses feel about deceased patients and end-of-life care, the
      nursing discharge summaries of 115 sequential patients who died in the
      respiratory division of a Japanese university hospital were reviewed. When
      compared to discharge summaries of patients with non-malignant illness, a
      significantly higher percentage of discharge summaries of those with malignant
      illnesses documented support from family members (P = 0.0166), patient's hope for
      cure (P = 0.0206), and patient anxiety (P = 0.0258). As difficult situations stay
      with nurses as memories, it is important for both new graduates and skilled
      nurses to document their feelings in difficult clinical situations.

PMID- 12225356
TI  - A sense of tumour for the immune system.

PMID- 12225357
TI  - Regulation of tumour immunity by CD25+ T cells.

PMID- 12225358
TI  - Bugs as drugs for cancer.

PMID- 12225359
TI  - Immunological weapons against acute myeloid leukaemia.
AB  - A better understanding of the biology of malignant cells and of the host immune
      system together with dramatic advances in technology have led to the design of
      innovative immune-mediated approaches to control neoplastic clones, including
      various haematological malignancies. One of the major problems with conventional
      cancer therapies is their inability to eradicate residual cancer cells that are
      resistant to therapy, hence immune intervention might improve the clinical
      outcome of patients. This mini-review will focus mainly on immunological
      approaches to the therapy of acute myeloid leukaemia (AML), a subset of a much
      larger family of leukaemias. Immune-mediated approaches ranging from allogeneic
      lymphocyte transplants to cytokine therapy, immune-gene therapy and vaccination
      by dendritic-cell-based vaccines will be discussed.

PMID- 12225361
TI  - Insight into the potential for DNA idiotypic fusion vaccines designed for
      patients by analysing xenogeneic anti-idiotypic antibody responses.
AB  - DNA vaccines induce immune responses against encoded proteins, and have clear
      potential for cancer vaccines. For B-cell tumours, idiotypic (Id) immunoglobulin
      encoded by the variable region genes provides a target antigen. When assembled as
      single chain Fv (scFv), and fused to an immunoenhancing sequence from tetanus
      toxin (TT), DNA fusion vaccines induce anti-Id antibodies. In lymphoma models,
      these antibodies have a critical role in mediating protection. For application to
      patients with lymphoma, two questions arise: first, whether pre-existing antibody
      against TT affects induction of anti-scFv antibodies; second, whether individual
      human scFv fusion sequences are able to fold consistently to generate antibodies
      able to recognize private conformational Id determinants expressed by tumour
      cells. Using xenogeneic vaccination with scFv sequences from four patients, we
      have shown that pre-existing anti-TT immunity slows, but does not prevent, anti
      Id antibody responses. To determine folding, we have monitored the ability of
      nine DNAscFv-FrC patients' vaccines to induce xenogeneic anti-Id antibodies.
      Antibodies were induced in all cases, and were strikingly specific for each
      patient's immunoglobulin with little cross-reactivity between patients, even when
      similar VH or VL genes were involved. Blocking experiments with human serum
      confirmed reactivity against private determinants in 26-97% of total antibody.
      Both immunoglobulin G1 (IgG1) and IgG2a subclasses were present at 1.3 : 1-15 : 1
      consistent with a T helper 2-dominated response. Xenogeneic vaccination provides
      a simple route for testing individual patients' DNAscFv-FrC fusion vaccines, and
      offers a strategy for production of anti-Id antibodies. The findings underpin the
      approach of DNA idiotypic fusion vaccination for patients with B-cell tumours.

PMID- 12225360
TI  - All in the head: obstacles for immune rejection of brain tumours.

PMID- 12225362
TI  - Cytokines in Lyme borreliosis: lack of early tumour necrosis factor-alpha and
      transforming growth factor-beta1 responses are associated with chronic
      neuroborreliosis.
AB  - The clinical outcome of the tick born infection Lyme borreliosis seems to be
      influenced by the type of immune response mounted during the disease, as
      suggested by various animal models. Here we report the serum and cerebrospinal
      fluid levels of tumour necrosis factor-alpha (TNF-alpha), transforming growth
      factor beta1 (TGF-beta1) and interleukin-6 (IL-6) in samples drawn at different
      disease intervals during the course of non-chronic neuroborreliosis (n=10),
      chronic neuroborreliosis (n=15), erythema migrans (n=8, serum only) and controls
      (n=7). When comparing early neuroborreliosis cerebrospinal fluid samples,
      significantly higher levels of TNF-alpha were found in non-chronic patients than
      in chronic patients (P<0.05). Moreover, TGF-beta1 was increased in the early
      serum samples of non-chronic patients, as compared to chronic patients (P<0.01).
      Elevated serum levels of TGF-beta1 were also found in erythema migrans as
      compared to neuroborreliosis and controls (P<0.05). The high TNF-alpha levels
      noted in early cerebrospinal fluid samples of non-chronic patients only, possibly
      reflects an ongoing pro-inflammatory immune response in the central nervous
      system, which could be beneficial in eliminating disease. High serum levels of
      TGF-beta1 probably mirror an anti-inflammatory response, which might play a role
      in controlling the systemic immune response.

PMID- 12225363
TI  - Characterizing a soluble survival signal for activated lymphocytes from CD14+
      cells.
AB  - T-cell activation requires at least two signals: antigen and a costimulatory
      signal. As antigen-presenting cells play an important role in this area, the role
      of CD14+ cells in T-cell activation, proliferation and activation-induced cell
      death (AICD) was investigated. Using phytohaemagglutinin (PHA) activation, it was
      found that CD14+ cell depletion resulted in significantly greater AICD, decreased
      lymphocyte growth and up-regulated interleukin-2 (IL-2) secretion. However, T
      cell activation was delayed according to the expression of CD69 and CD25.
      Dynabeads conjugated with anti-CD14 monoclonal antibody (mAb) bound CD14+ cells
      and induced secretion of IL-1beta, tumour necrosis factor-alpha (TNF-alpha),
      transforming growth factor-beta (TGF-beta) and IL-6, but not IL-2, IL-12 or IL
      15. Supernatants were collected from Dynabeads-activated CD14+ cell cultures and
      designated as 'CD14 cocktails'. Addition of CD14 cocktails to CD14+ cell-depleted
      mononuclear cell cultures reversed the increased AICD, decreased lymphocyte
      growth and increased IL-2 secretion. Depletion of IL-1beta and TNF-alpha in the
      CD14 cocktails by panning followed by blocking with the corresponding mAbs had no
      effect on the active AICD protection. TGF-beta was determined not to be the
      active factor owing to the presence of >1.0 ng of TGF-beta in the media for
      culturing both CD14+ and CD14- peripheral blood mononuclear cells (PBMC). The
      CD14 cocktails did not contain IL-12 and IL-15. Depletion of IL-6 with panning
      followed by blocking residual IL-6 with anti-IL-6 mAb significantly reduced the
      protective effect of the CD14 cocktails. Human recombinant IL-6 also partially
      reversed the effects of CD14+ cell depletion on AICD, lymphocyte growth and IL-2
      secretion. The data suggest that IL-6 is one of the active factors in the
      survival signal from CD14+ cells.

PMID- 12225364
TI  - The haemopoietic growth factor, Flt3L, alters the immune response induced by
      transcutaneous immunization.
AB  - Topical application of antigen induces antigen-specific humoral and cellular
      immune responses. In this study we examined whether expansion of dendritic cells
      (DC) by Flt3 ligand (Flt3L) treatment influences the induction of immune
      responses following transcutaneous immunization. Mice were treated
      intraperitoneally with Flt3L or phosphate-buffered saline (PBS) and immunized
      transcutaneously with hen egg lysozyme (HEL). Flt3L-treated mice developed lower
      HEL-specific cellular and humoral immune responses than PBS-treated mice.
      However, in the presence of cholera toxin (CT), a potent adjuvant for mucosal and
      transcutaneous immunization, Flt3L-treated mice developed significantly higher
      cellular and humoral immune responses to HEL when compared to PBS-treated mice.
      We assessed whether the immunomodulatory effects of CT were a result of
      activation of epidermal dendritic cells (Langerhans' cells; LC). Our results
      indicate that within 8-12 hr of topical application of CT, epidermal LC cells
      lose their dendritic morphology and become rounder in appearance. In addition, we
      observed enhanced expression of major histocompatibility complex (MHC) class II,
      and of adhesion molecules CD11c and intracellular adhesion molecule-1 (ICAM-1).
      Our observations support the concept that the state of activation of DC in the
      skin is central to the regulation of immune responses. This information is
      relevant to the design of effective transcutaneous vaccination strategies.

PMID- 12225366
TI  - krox-20/egr-2 is up-regulated following non-specific and homophilic adhesion in
      rat macrophages.
AB  - Macrophages are known to adhere to a plastic dish via beta2 integrin (CR3) and
      scavenger receptors. Although their functions such as phagocytosis, endocytosis,
      and nitric oxide production have been investigated on adherent macrophages in
      vitro, very little is known about intracellular signals triggered by adhesion to
      a plastic dish. Recently we reported that the mRNA level of krox-20/egr-2 was
      significantly increased in rat alveolar macrophages following exposure to fibrous
      titanium dioxide particles. In the present study we report that up-regulation of
      krox-20/egr-2 gene expression following adhesion to a plastic dish and homophilic
      adhesion in rat alveolar macrophages and rat macrophage cell line, NR8383. The
      mRNA level of krox-20/egr-2 increased with a peak 1 hr after adhesion to a
      plastic dish in both cell types. Piceatannol inhibited tyrosine-phosphorylation
      of Syk and decreased both adhesion and krox-20/egr-2 mRNA level. In contrast
      staurosporine, a serine/threonine kinase inhibitor, increased adherence of
      macrophages and yet prohibited the adhesion-dependent increase in krox-20/egr-2
      gene expression. When NR8383 cells are cultured in suspension, the cells
      aggregated naturally and produced cell clumps. The mRNA level of krox-20/egr-2
      also increased in response to the homophilic intercellular adhesion. The
      increased mRNA level of krox-20/egr-2 was not caused by inflammatory stimuli,
      because lipopolysaccharide did not affect the aggregation-dependent up-regulation
      of krox-20/egr-2 gene. The up-regulation of krox-20/egr-2 gene due to the
      homophilic cell aggregation was also inhibited either by piceatannol or
      staurosporine. Those results suggest that krox-20/egr-2 gene expression is
      triggered by sensing non-specific and homophilic cellular adhesion and the
      following phosphorylation of signal transducing proteins including Syk and
      staurosporine-inhibitable kinases.

PMID- 12225365
TI  - Regulation of adhesion of AML14.3D10 cells by surface clustering of beta2
      integrin caused by ERK-independent activation of cPLA2.
AB  - We examined the role of cell surface clustering of beta2-integrin caused by
      protein kinase C (PKC)-activated-cPLA2 in adhesion of eosinophilic AML14.3D10
      (AML) cells. Phorbol 12-myristate 13-acetate (PMA) caused time- and concentration
      dependent adhesion of AML cells to plated bovine serum albumin (BSA), which was
      blocked by anti-CD11b or anti-CD18 monoclonal antibodies (mAb) directed against
      beta2-integrin. Inhibition of PKC with Ro-31-8220 or rottlerin blocked PMA
      induced cell adhesion in a concentration-dependent fashion. Inhibition of
      cytosolic phospholipase A2 (cPLA2) with trifluoromethyl ketone or methyl
      arachidonyl fluorophosphonate also blocked PMA-induced cell adhesion. PMA caused
      time-dependent p42/44 mitogen-activated protein kinase (MAPK) (ERK)
      phosphorylation in these cells. U0126, a MAPK/extracellular signal-regulated
      protein kinase kinase (MEK) inhibitor, at the concentrations that blocked PMA
      induced ERK phosphorylation, had no effect on PMA stimulated AML cell adhesion.
      Neither p38 MAPK nor c-Jun N-terminal kinase (JNK) was phosphorylated by PMA. PMA
      also caused increased cPLA2 activity, which was inhibited by Ro-31-8220, but not
      U0126. Confocal immunofluorescence microscopy showed that PMA caused clustering
      of CD11b on the cell surface, which was blocked by either PKC or cPLA2
      inhibition. PMA stimulation also caused up-regulation of CD11b on the AML cell
      surface. However, this up-regulation was not affected by cPLA2- or PKC
      inhibition. Using the mAb, CBRM1/5, we also demonstrated that PMA does not induce
      the active conformation of CD11b/CD18. Our data indicate that PMA causes AML cell
      adhesion through beta2-integrin by PKC activation of cPLA2. This pathway is
      independent of MEK/ERK and does not require change of CD11b/CD18 to its active
      conformation. We find that avidity caused by integrin surface clustering - rather
      than conformational change or up-regulation of CD11b/CD18 - causes PMA stimulated
      adhesion of AML cells.

PMID- 12225367
TI  - Mechanism of induction of complement susceptibility of erythrocytes by spider and
      bacterial sphingomyelinases.
AB  - We have recently shown that the sphingomyelinase toxins P1 and P2 from the venom
      of the spider Loxosceles intermedia induce complement (C)-dependent lysis of
      autologous erythrocytes by induction of the cleavage of cell surface glycophorins
      through activation of an endogenous metalloproteinase facilitating the activation
      of the alternative pathway of C. Phospholipase D (PLD) from Corynebacterium
      pseudotuberculosis shows some degree of homology with the spider
      sphingomyelinases and can induce similar clinical symptoms to those observed
      after spider envenomation. The aim of this study was to investigate if the
      bacterial PLD-induced haemolysis of human erythrocytes was C dependent and if
      cleavage of glycophorins occurred. We show here that haemolysis of both PLD- and
      P1-treated human erythrocytes was C dependent, but while PLD-mediated haemolysis
      was dependent on activation of the classical pathway of C, P1 induced lysis via
      both the classical and alternative pathways. P1, but not PLD, induced cleavage of
      glycophorins and no change in expression of complement regulators was induced by
      either of the toxins. In both cases, annexin V binding sites were exposed,
      suggesting that the membrane asymmetry had been disturbed causing exposure of
      phosphatidylserine to the cell surface. Our results suggest that C susceptibility
      induced by L. intermedia and C. pseudotuberculosis PLD is a result of exposure of
      phosphatidylserine, and the higher potency of P1 toxin can be explained by its
      additional effect of cleavage of glycophorins.

PMID- 12225368
TI  - Loxosceles spider venom induces metalloproteinase mediated cleavage of MCP/CD46
      and MHCI and induces protection against C-mediated lysis.
AB  - We have recently shown that sphingomyelinase D toxins from the spider Loxosceles
      intermedia induce Complement (C) -dependent haemolysis of autologous erythrocytes
      by the induction of cleavage of cell-surface glycophorins through activation of a
      membrane-bound metalloproteinase. The aim of this study was to investigate the
      effects of these toxins on C-regulator expression and the C-resistance of
      nucleated cells. Cells were incubated with Loxosceles venom/toxins and the
      expression of C-regulators was assessed by flow cytometry. A reduced expression
      of membrane co-factor protein (MCP) was observed, while expression of decay
      accelerating factor (DAF) and CD59 was not affected. Analysis of other cell
      surface molecules showed a reduced expression of major histocompatibility complex
      I (MHCI). Western blotting showed that a truncated form of MCP was released into
      the supernatant. Release could be prevented by inhibitors of metalloproteinases
      of the adamalysin family but not by inhibitors specific for matrix
      metalloproteinases. Cleavage of MCP was induced close to or within the membrane
      as demonstrated by the cleavage of transmembrane chimeras of CD59 and MCP.
      Although the venom/toxins induced a release of MCP, the C-susceptibility was
      decreased. The mechanism of this induction of resistance may involve a change in
      membrane fluidity induced by the sphingomyelinase activity of the toxin/venom
      and/or involvement of membrane-bound proteases. The soluble forms of MCP found in
      tissues and body under pathological conditions like cancer and autoimmune
      diseases may be released by a similar mechanism. The identity of the
      metalloproteinase(s) activated by the spider venom and the role in pathology of
      Loxoscelism remains to be established.

PMID- 12225369
TI  - Flavoxobin, a serine protease from Trimeresurus flavoviridis (habu snake) venom,
      independently cleaves Arg726-Ser727 of human C3 and acts as a novel, heterologous
      C3 convertase.
AB  - We have recently shown that crude Trimeresurus flavoviridis (habu snake) venom
      has a strong capability for activating the human alternative complement system.
      To identify the active component, the crude venom was fractionated and purified
      by serial chromatography using Sephadex G-100, CM-cellulose C-52,
      diethylaminoethyl-Toyopearl 650M, and Butyl-Toyopearl, and the active fractions
      were evaluated by the C3a-releasing and soluble membrane attack complex-forming
      activities. Two peak fractions with the highest activities were detected after
      gel filtration and ion exchange chromatography, and the first fraction was
      purified to homogeneity. The homogeneous protein was examined for its N-terminal
      amino acid sequence by Edman degradation. The determined sequence of 25 amino
      acids completely coincided with that of a previously reported serine protease
      with coagulant activity, flavoxobin, purified from the same snake venom. To
      elucidate the molecular mechanism of the complement activation, the reactive
      products of the mixture of the purified human C3 and flavoxobin were examined by
      sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The digesting pattern
      revealed that flavoxobin cleaves the alpha chain of the C3 molecule into two
      fragments. The N-terminal amino acid sequences for the remnant fragments of C3
      disclosed that flavoxobin severs the human C3 at the Arg726-Ser727 site to form
      C3b and C3a the way C3bBb, the human alternative C3 convertase, does. In
      conclusion, flavoxobin acts as a novel, heterologous C3 convertase that
      independently cleaves human C3 and kick-starts the complement cascade.

PMID- 12225370
TI  - Conjunctival macrophage-mediated influence of the local and systemic immune
      response after corneal herpes simplex virus-1 infection.
AB  - Recently it has been shown that selective subconjunctival macrophage depletion
      reduced the incidence and severity of stromal herpes simplex virus (HSV)
      keratitis in mice. In this study, we examined the effect of conjunctival
      macrophage depletion on the corneal and systemic T-cell-mediated immune response.
      BALB/c mice were treated with subconjunctival injections of dichloromethylene
      diphosphonate (Cl2MDP)-liposomes (Cl2MDP-LIP) or phosphate-buffered saline (PBS)
      7 and 2 days before corneal infection with 105 plaque-forming units (PFU) of HSV
      1 (KOS strain). Interferon (IFN)-gamma, interleukin (IL)-2, and IL-4 production
      in the cornea was analysed by enzyme-linked immunosorbent assay (ELISA), and
      cytokine mRNA levels (IFN-gamma, IL-4) were measured by semiquantitative reverse
      transcription-polymerase chain reaction (RT-PCR). Cell culture supernatants from
      submandibular lymph nodes were analysed by ELISA for expression of IFN-gamma, IL
      2, and IL-4 and by bioassay for IL-6. The HSV-1-specific proliferative response
      of lymphocytes from regional lymph nodes and the delayed-type hypersensitivity
      (DTH) response were tested after corneal infection. Virus-neutralizing antibody
      titres and HSV-1-specific immunoglobulin G (IgG)2a/IgG1-ratios were measured.
      Cytokine mRNA expression (IFN-gamma, IL-4) and secretion (IFN-gamma, IL-2, IL-4)
      in the corneas were decreased after HSV-1 corneal infection in the macrophage
      depleted mice. The secretion of IFN-gamma and IL-2 was decreased in the regional
      lymph nodes from Cl2MDP-LIP-treated animals (P<0.05). Furthermore, Cl2MDP-LIP
      treated mice had decreased HSV-1 specific proliferative responses (P<0.05) and
      DTH response after corneal HSV-1 infection (P<0.05). The virus-neutralizing serum
      antibody levels (P<0.05) increased while the HSV-1 specific IgG2a/IgG1-ratio was
      unaffected after macrophage depletion. Macrophage depletion did not induce a
      shift between the T helper 1 (Th1) and Th2 response in this HSK model. The data
      suggest that conjunctival macrophage functions are enhancing the T-cell-mediated
      immune response after corneal infection. This effect is at least in part
      responsible for the impaired course of herpetic keratitis after macrophage
      depletion.

PMID- 12225371
TI  - Glycoprotein B from strain 17 of herpes simplex virus type I contains an
      invariant chain homologous sequence that binds to MHC class II molecules.
AB  - Major histocompatibility complex class I (MHCI) molecules are major targets of
      virus evasion strategies because they introduce antigens from the biosynthesis
      pathway into the antigen-processing and presentation pathways for immune
      recognition by CD8+ T cells. Little is known about viral strategies that
      interfere with the MHC class II (MHCII) antigen presentation pathway. We
      identified a six amino acid sequence from type I herpes simplex virus (HSV-1)
      glycoprotein B (gB) that is identical to a sequence of human leucocyte antigen D
      (HLA-D) -associated invariant chain (Ii). In addition, this gB sequence is
      adjacent to a highly conserved HLA-DR1 binding motif. Both viral sequences
      together resemble the class II binding site of human Ii, consisting of a MHCII
      groove binding segment and a promiscuous binding site. We cloned gB from HSV-1
      strain 17 and demonstrate association of the virus envelope protein to three HLA
      DR allotypes. With chimeric Ii/gB fusion proteins we identified gB sequences that
      mediate promiscuous or allotype-specific binding to the HLA-DR peptide-binding
      domain. Mutation of two Lys residues in the viral segment of Ii/gB abolished
      promiscuous binding to HLA-DR heterodimers. The result indicates promiscuous
      binding of the virus sequence to HLA-DR molecules and suggests a potential for
      HSV-1 to manipulate antigen processing and presentation.

PMID- 12225372
TI  - Long-term kinetics of adult human antibody repertoires.
AB  - In healthy humans, antibody repertoires change during ontogeny and senescence.
      The dynamics of antibody repertoires among adults over a longer period of time in
      one and the same individual has, however, not been extensively studied. In this
      study we analysed peripheral blood samples from five healthy adults, taken over a
      period of 10 weeks and once 9 years later. A competitive, quantitative polymerase
      chain reaction (PCR) was developed to investigate short and long-term variations
      in VH gene family repertoires. Serum antibody levels to common self and non-self
      antigens were determined in samples taken at the same time-points as the cell
      samples to analyse possible correlations between molecular and serological
      expression profiles. We found a high degree of stability in the VH gene family
      repertoire over time as well as between individuals with a Caucasian background.
      A specific change in the usage of primarily the VH3 and VH5 gene families was
      observed in one individual at one time-point. The deviating pattern resembled the
      VH gene family utilization pattern observed in naturally activated B lymphocytes.
      The fluctuations in VH3 and VH5 gene family expression correlated with the
      presence of rheumatoid factor in serum. We discuss the possible influence of
      polyclonal, transient stimulation of B cells on VH gene repertoires, as measured
      in circulating B cells.

PMID- 12225373
TI  - Expression and regulation of the pattern recognition receptors Toll-like receptor
      2 and Toll-like receptor-4 in the human placenta.
AB  - The placenta constitutes a physical and immunological barrier against invading
      infectious agents and has been suggested to be a pregnancy-specific component of
      the innate immune system. The aim of this study was to investigate the presence
      and regulation of Toll-like receptors-2 and -4 (TLR2 and TLR4) in the human
      placenta, because these receptors are believed to be important for immune
      responses against pathogens. Twenty-eight placentas from normal term pregnancies
      were analysed with immunohistochemistry, which showed a strong immunoreactivity
      for TLR2 and TLR4 in the villous and the intermediate trophoblasts. The
      regulation of TLR2 and TLR4 by microbial stimulus was assessed by incubating
      explants of term chorionic villi with zymosan or lipopolysaccharide (LPS) and
      analysed with real-time reverse transcriptase-polymerase chain reaction.
      Stimulation with zymosan and LPS readily induced interleukin (IL)-6 and IL-8
      cytokine production in the placenta cultures, whereas TLR2 and TLR4 mRNA and
      protein expression remained at the same high level as in unstimulated explants.
      These data suggests a novel mechanism for the fetoplacental unit to interact with
      micro-organisms.

PMID- 12225376
TI  - Immunity to asexual blood stage malaria and vaccine approaches.
AB  - The development of a malaria vaccine seems to be a definite possibility despite
      the fact that even individuals with a life time of endemic exposure do not
      develop sterile immunity. An effective malaria vaccine would be invaluable in
      preventing malaria-associated deaths in endemic areas, especially amongst
      children less than 5 years of age and pregnant women. This review discusses our
      current understanding of immunity against the asexual blood stage of malaria -
      the stage that is responsible for the symptoms of the disease - and approaches to
      the design of an asexual blood stage vaccine.

PMID- 12225374
TI  - The modulatory effects of prostaglandin-E on cytokine production by human
      peripheral blood mononuclear cells are independent of the prostaglandin subtype.
AB  - The production of inflammatory mediators, relevant to (auto)immune diseases and
      chronic inflammatory conditions, can be modulated by dietary intake of n-3 and n
      6 long chain polyunsaturated fatty acids (PUFAs). It was suggested that these
      effects are related to the formation of different series of eicosanoids, in
      particular prostaglandin-E (PGE). In this study we investigated whether
      prostaglandin subtypes metabolized from arachidonic acid (PGE2), dihomo-gamma
      linolenic acid (PGE1) or eicosapentaenoic acid (PGE3) have different effects on T
      cell proliferation and cytokine production in vitro. Freshly isolated human
      peripheral blood mononuclear cells (PBMC) were stimulated with concanavalin A
      (ConA) or lipopolysaccharide (LPS) in the presence or absence of exogenous PGE1,
      PGE2 or PGE3. We found that tumour necrosis factor-alpha (TNF-alpha), interferon
      gamma (IFN-gamma) and to a lesser extent interleukin (IL)-10 production was
      inhibited by all PGE-subtypes in ConA-stimulated PBMC concomitant with unaffected
      IL-2 levels. The modulated cytokine production of ConA stimulated cells was
      independent of T-cell proliferation. PGE2 and PGE1 moderately stimulated
      proliferation, while PGE3 inhibited the proliferative response to some extent. In
      LPS-stimulated PBMC, TNF-alpha production was inhibited by all PGE-subtypes,
      whereas IL-6 remained unaffected and IL-10 production was increased. Time course
      experiments on the effects of PGE-subtypes on cytokine production after ConA or
      LPS stimulation showed these effects to be time dependent, but indifferent of the
      prostaglandin subtype added. Overall, the modulatory effects of PGE on cytokine
      production were irrespective of the subtype. This may implicate that the
      immunomodulatory effects of PUFAs, with respect to cytokine production, are not
      caused by a shift in the subtype of PGE.

PMID- 12225377
TI  - Interferon-gamma enhances cytotoxic T lymphocyte recognition of endogenous
      peptide in keratinocytes without lowering the requirement for surface peptide.
AB  - Keratinocytes expressing the human papillomavirus (HPV) type 16 E7 protein, as a
      transgene driven by the K14 promoter, form a murine model of HPV-mediated
      epithelial cancers in humans. Our previous studies have shown that K14E7
      transgenic skin grafts onto syngeneic mice are not susceptible to immune
      destruction despite the demonstrated presence of a strong, systemic CTL response
      directed against the E7 protein. Consistent with this finding, we now show that
      cultured, E7 transgenic keratinocytes (KC) express comparable endogenous levels
      of E7 protein to a range of CTL-sensitive E7-expressing cell lines but are not
      susceptible to CTL-mediated lysis in vitro. E7 transgenic and non-transgenic KC
      are susceptible to conventional mechanisms of CTL-mediated lysis, including
      perforin and Fas/FasL interaction when an excess of exogenous peptide is
      provided. The concentration of exogenous peptide required to render a cell
      susceptible to lysis was similar between KC and other conventional CTL targets
      (e.g. EL-4), despite large differences in H-2Db expression at the cell surface.
      Furthermore, exposure of KC to IFN-gamma increased H-2Db expression, but did not
      substantially alter the exogenous peptide concentration required to sensitize
      cells for half maximal lysis. In contrast, the lytic sensitivity of transgenic KC
      expressing endogenous E7 is modestly improved by exposure to IFN-gamma. Thus,
      failure of CTL to eliminate KC expressing endogenous E7, and by inference
      squamous tumours expressing E7, may reflect the need for a sustained, local
      inflammatory environment during the immune effector phase.

PMID- 12225378
TI  - Synergy of type I interferon-A6 and interferon-B naked DNA immunotherapy for
      cytomegalovirus infection.
AB  - Delivery of type I IFN transgenes by naked DNA immunization can protect against
      cytomegalovirus infection and myocarditis. Here, we investigate IFN transgene
      expression, antiviral efficacy, and immunomodulation of myocarditis using various
      treatment regimes in a mouse CMV model. In vivo expression of the IFN transgene
      was observed in the sera for 35 days post-DNA inoculation. Prophylactic IFN-A6
      and IFN-B DNA treatment for 14 days prior to murine cytomegalovirus (MCMV)
      infection was more efficacious in significantly reducing viral titres, than 2
      days prior to or 2 days post-virus infection. Similarly, IFN-A6 DNA treatment
      commencing 14 days prior to virus infection was superior in suppressing both
      acute and chronic myocarditis. Furthermore, reduction of autoantibody titres was
      more pronounced when IFN was administered 14 days prior to viral infection.
      Combinational IFN gene therapy was assessed for synergy between IFN subtypes.
      Combination treatment with either IFN-A6/A9 or IFN-A6/B greatly reduced spleen
      viral titres while IFN-A6/B and IFN-A9/B reduced virus replication in the liver.
      Only IFN-A6/A9 and IFN-A9/B reduced acute viral myocarditis, whereas IFNA6/B
      treatment was most efficacious for autoimmune chronic myocarditis. Finally,
      treatment with IFN-A6 DNA 2 weeks post-MCMV infection proved effective at
      inhibiting the development of chronic autoimmune myocarditis. These findings
      suggest that immunomodulation of both antiviral and autoimmune responses by IFN
      DNA immunization may be an avenue for improved viral immunotherapy.

PMID- 12225379
TI  - TNF contributes to the immunopathology of perforin/Fas ligand double deficiency.
AB  - Perforin (pfp)/Fas ligand (FasL) double-deficient mice have previously been shown
      to be infertile, lose weight and die prematurely due to tissue destruction caused
      by a significant inflammatory infiltrate of monocytes/macrophages and T cells.
      Herein we have compared disease progression in mice additionally deficient in the
      inflammatory mediator TNF. Unlike pfp/FasL double-deficient mice (TNF+/+ pfp-/-
      gld), mice lacking functional TNF, FasL and pfp (TNF-/- pfp-/- gld) were
      comparatively fertile, with the majority of mice not suffering severe
      pancreatitis or hysterosalphingitis in the first 5 months of life. The mean
      lifespan of TNF-/- pfp-/- gld mice was 217 +/- 79 days compared with 69 +/- 10
      days for TNF+/+ pfp-/- gld mice and the majority of moribund TNF-/- pfp-/- gld
      mice appeared to die as a result of severe pancreatitis, suggesting that loss of
      TNF was not completely protective. At 8 weeks of age, characteristics associated
      with the gld phenotype, such as expansion of B220+ CD4- CD8- T cells,
      lymphadenopathy and hypergammaglobulinemia were comparable between TNF+/+ pfp-/-
      gld and TNF-/- pfp-/- gld mice, although the lymphoid organs of TNF+/+ pfp-/- gld
      mice contained greater numbers of B220+ CD4- CD8- T cells, macrophages and T
      cells. We conclude that TNF is necessary for the full manifestation of immune
      dysregulation caused by pfp/FasL-deficiency, in particular in the early and
      overwhelming tissue infiltration and destruction caused by inflammatory cells.

PMID- 12225380
TI  - Embryonic macrophages of early rat yolk sac: Immunohistochemistry and
      ultrastructure with reference to endodermal cell layer.
AB  - Macrophages are multifunctional cells that participate in numerous biological
      processes; they actively phagocytose foreign particles and cell debris. Embryonic
      tissue macrophages are present at early stages of mammalian development; their
      ontogeny and function is still under investigation. Our study used
      immunohistochemistry and electron microscopy to investigate early rat yolk sac
      macrophages using mouse antirat macrophage monoclonal antibodies (mAb) Mar 1 and
      Mar 3 produced by our laboratory. Mar 3 mAb revealed the first emergence of
      immature macrophages in the rat yolk sac at fetal day nine coinciding with the
      beginning of yolk sac haemopoiesis that consisted mainly of erythropoiesis, while
      Mar 1 mAb detected specifically rat yolk sac macrophages at about the 13th to
      14th day of gestation. Immunoreactivity against Mar mAbs was mainly located in
      the yolk sac endodermal cell layer, which may signify endodermal origin of the
      yolk sac macrophages. Ultrastructurally mature yolk sac macrophages contained
      numerous endocytic vesicles or vacuoles, well-developed Golgi saccules and many
      electron dense granules in their cytoplasm and a number of microvillous
      projections from the cell surface. After establishment of the circulation between
      yolk sac and embryo, Mar 3 positive cells were also demonstrated inside fetal
      undifferentiated mesenchymal tissue at fetal day 12. The study demonstrated the
      first emergence of immature yolk sac macrophages being among the earliest
      haemopoietic cells formed in mammalian development. Thus, Mar mAbs managed to
      detect macrophage differentiation antigens through their development early in the
      rat yolk sac.

PMID- 12225381
TI  - Travellers in many guises: the origins and destinations of dendritic cells.
AB  - The migratory behaviour of dendritic cells (DC) is tightly linked to their
      differentiation state. Precursor DC constitutively repopulate normal tissues from
      the bloodstream, and are recruited in elevated numbers to sites of inflammation.
      Whilst maturing in response to antigenic stimulation, DC acquire the capability
      to enter lymph nodes via afferent lymphatic vessels, thus facilitating their
      presentation of antigen to naive T cells. Peripheral blood monocytes constitute a
      second DC precursor population, which during an inflammatory response are
      recruited to the affected site where some differentiate into functional DC. The
      availability of separate DC precursor populations is thought to be significant
      for the character, amplification and perpetuation of the resultant immune
      response. In addition, the balance between steady-state trafficking of
      incompletely activated DC bearing self-antigens from the periphery, and the
      migration of fully mature DC from inflammatory sites into lymph nodes might have
      profound effects upon tolerance induction and activation of T cells,
      respectively.

PMID- 12225382
TI  - The role of dendritic cell subsets in selection between tolerance and immunity.
AB  - Dendritic cells (DC) are considered nature's adjuvants. They are potent
      stimulators of naive T cells and key inducers of primary immune responses. In
      recent times it has become clear that they can also play a central role in the
      development of T cell tolerance. Further complicating our understanding of DC
      function is the realization that DC can no longer be viewed as a homogeneous cell
      type. Rather, they exist as a complex mixture of strikingly different cell
      populations. The mechanisms that drive the conflicting immunological outcomes of
      tolerance and immunity have been the subject of intense scrutiny in recent years,
      most recently in terms of how the various DC subsets are involved in these
      events. Here we review recent experiments that provide insights into how DC
      subsets control the outcome of T cell activation and in so doing select between
      immunity and tolerance induction.

PMID- 12225383
TI  - Experimental models linking dendritic cell lineage, phenotype and function.
AB  - One of the important issues in dendritic cell (DC) biology today is how DC
      control the fate of T cells. Our data suggest that an important branch point in
      determining T cell fate is the decision between deletion and memory. We have
      previously hypothesized that this binary decision is determined by contact with
      DC derived from lymphoid- versus myeloid-restricted progenitors. However, the
      false attribution of CD8alpha expression as a reliable marker of lymphoid origin
      has underpinned a number of studies in which DC expressing CD8alpha did not
      induce deletion, thereby clouding the issue of whether deletion is indeed a
      function of lymphoid DC. By returning to basics, that is, functional testing of
      the progeny of lymphoid- and myeloid-restricted progenitors in vivo, we hope to
      provide clear evidence of the in vivo roles of lymphoid and myeloid DC subsets,
      independent of assumptions about the surface phenotypes they can assume.

PMID- 12225384
TI  - Immature, but not inactive: the tolerogenic function of immature dendritic cells.
AB  - The induction of antigen-specific T cell tolerance and its maintenance in the
      periphery is critical for the prevention of autoimmunity. Recent evidence shows
      that dendritic cells (DC) not only initiate T cell responses, but are also
      involved in silencing of T cell immune responses. The functional activities of DC
      are mainly dependent on their state of activation and differentiation, that is,
      terminally differentiated mature DC can efficiently induce the development of T
      effector cells, whereas immature DC are involved in maintenance of peripheral
      tolerance. The means by which immature DC maintain peripheral tolerance are not
      entirely clear, however, their functions include the induction of anergic T
      cells, T cells with regulatory properties as well as the generation of T cells
      that secrete immunomodulatory cytokines. This review summarizes the current
      knowledge about the immunoregulatory role of immature DC that might act as
      guardians for the induction and maintenance of T cell tolerance in the periphery.

PMID- 12225385
TI  - The interplay of dendritic cell subsets in systemic lupus erythematosus.
AB  - Dendritic cells (DC) control immunity and tolerance. Hence, we surmised that
      systemic lupus erythematosus (SLE), a systemic autoimmune disease with
      autoreactive T and B cells, might be due to DC alterations. Based on our
      findings, we are proposing a model of SLE where autoimmune responses are driven
      by unabated activation of myeloid DC through IFN-alpha produced by plasmacytoid
      DC. Thus, interplay between DC subsets might represent a key component of SLE
      pathogenesis.

PMID- 12225386
TI  - Chemokines and dendritic cells: a crucial alliance.
AB  - Dendritic cells (DC) are bone marrow-derived professional antigen-presenting
      cells that function as sentinels of the immune system. Their importance in
      immunity resides in their unique ability to prime or tolerize T lymphocytes,
      thereby initiating or inhibiting immune responses. They reside in all tissues and
      organs and upon appropriate activation, migrate to secondary lymphoid organs to
      present antigen to T lymphocytes in the T cell zones. Because of this central
      role in T cell activation, there is a great deal of interest in using DC
      therapeutically to deliver positive or negative signals to the immune system. The
      DC system is critically dependent on the ability of DC at different stages of
      maturation to respond to a range of soluble and cell-bound signals, including
      members of the chemokine gene superfamily. This review will describe the
      interactions between DC and the chemokine system.

PMID- 12225389
TI  - Cutaneous microvascular blood flow and reactivity in patients with homozygous
      sickle cell anaemia.
AB  - Homozygous sickle cell anaemia (SS disease) involves a high prevalence of skin
      ulcerations, and background experience concerning the cutaneous microcirculatory
      flux and reactivity in this disease is very limited. We investigated, by laser
      Doppler velocimetry, the microcirculatory cutaneous blood flow and vasoreactivity
      in 17 patients with SS disease but no cutaneous trophic changes, vs. the
      corresponding values in 18 normal matched controls. The laser-Doppler probe was
      placed on the foot dorsum, and recordings were made in the supine and dependent
      positions, and after post-ischaemic hyperaemia. The venoarteriolar reflex was
      calculated as the difference between the fluxes in the supine and dependent
      positions. In both positions, patients with SS disease exhibited clear
      vasodilation, with larger cutaneous fluxes than those of the controls (P=0.024
      and 0.0009, respectively). The venoarteriolar reflex, expressed as a percentage
      of the resting supine flux, was lower in the patients (P=0.0004). These
      impairments of the microcirculatory fluxes, which combine a vasodilated state
      with abnormal vasoreactivity, resemble those observed in patients with chronic
      venous insufficiency and might be crucial in determining the pathogenesis of the
      skin ulcerations that occur in SS disease. Laser-Doppler velocimetry seems a
      suitable non-invasive technique for investigating such cutaneous microangiopathy.

PMID- 12225387
TI  - Dendritic cells, chemokine receptors and autoimmune inflammatory diseases.
AB  - Dendritic cells (DC) have been implicated in the induction of autoimmune diseases
      and have been identified in lesions associated with several autoimmune
      inflammatory diseases. Since DC are regarded as the professional antigen
      presenting cell (APC) of the immune system and the only APC capable of activating
      naive T cells, they are likely to play a significant role in breaking tolerance
      of self-reactive lymphocytes and in supporting autoimmune responses in these
      diseases. A number of studies have revealed that small molecular weight
      chemotactic proteins known as chemokines are present within the autoimmune
      lesions and may contribute to the recruitment not only of DC populations, but
      also of immune cells such as T cells, B cells, neutrophils and monocytes into the
      site, and to the formation of organized lymphoid tissue structures within the
      target organ. The focus of this review will be a discussion of the role of
      chemokines in the recruitment of DC in human autoimmune inflammatory disorders,
      specifically the trafficking of DC into the inflammatory sites and the subsequent
      migration of differentiated DC from the inflammatory sites into the draining
      lymph nodes. Once DC are properly positioned within the lymph nodes, circulating
      antigen specific naive T cells can interact with DC and become activated,
      clonally expanded and stimulated to undergo differentiation into antigen
      experienced memory T cells. Subsequent reactivation of memory T cells that enter
      the autoimmune lesions by DC present in the inflammatory lesion is thought to
      play a central role in tissue inflammation.

PMID- 12225391
TI  - Iron deficiency anaemia in young women.
AB  - OBJECTIVES: The expression density of GPIaIIa, the primary platelet collagen
      receptor (integrin alpha2beta1), is linked to two polymorphisms (GPIa-807C/T and
      HPA-5a/b). During evolution a gene shift from the genotypes GPIa-807CC-HPA-5bb to
      the genotypes GPIa-807CT-HPA-5aa has taken place. The aim of the study was to
      assess whether iron deficiency anaemia (e.g. increased blood loss) in young women
      could be associated with a specific genotype, indicating a role as potential
      evolutionary selection factor. STUDY DESIGN: Women between 18 and 40 yr of age
      presenting for their first blood donation were asked about alimentary habits and
      use of oral contraception. Haemoglobin and serum ferritin were measured and the
      GPIa-C807T and HPA-5 genotypes were determined. RESULTS: Two hundred women were
      included and grouped according to the WHO definition for iron deficiency anaemia
      (haemoglobin <121 g L(-1) and ferritin <15 microg L(-1)). Eight women fulfilled
      both WHO-criteria for iron deficiency anaemia, 145 women fulfilled none. No
      differences regarding age, use of oral contraceptives, alimentary habits, and HPA
      5 were found between the groups. The GPIa-807CC genotype was strongly over
      represented in the WHO-anaemic women as compared to the non-WHO-anaemic women
      (87.5% vs. 33.1%, P=0.003). CONCLUSION: Iron deficiency anaemia in young women
      might have been the evolutionary disadvantage causing the gene shift from GPIa
      807CC to 807CT.

PMID- 12225390
TI  - Iron status in Danish men 1984-94: a cohort comparison of changes in iron stores
      and the prevalence of iron deficiency and iron overload.
AB  - BACKGROUND AND OBJECTIVES: From 1954 to 1987, flour in Denmark was fortified with
      30 mg carbonyl iron per kg. This mandatory fortification was abolished in 1987.
      The aim of this study was to compare iron status in Danish men before and after
      abolition of iron fortification. METHODS: Iron status (serum ferritin,
      haemoglobin), was assessed in population surveys in Copenhagen County during 1983
      84 comprising 1324 Caucasian men (1024 non-blood-donors, 300 blood donors) and in
      1993-94 comprising 1288 Caucasian men (1103 non-blood-donors, 185 donors),
      equally distributed in age cohorts of 40, 50, 60 and 70 yr. RESULTS: In the 1984
      survey median serum ferritin values in the four age cohorts in non-blood-donors
      were 136, 141, 133 and 111 microg/L, and in the 1994 survey 177, 173, 186 and 148
      microg L(-1), respectively. The difference was significant in all age groups
      (P<0.001). There was no significant difference between the two surveys concerning
      the prevalence of small iron stores (ferritin 16-32 micro g L(-1)), depleted iron
      stores (ferritin <16 microg L(-1)) or iron-deficiency anaemia (ferritin <13
      microg L(-1) and Hb <5th percentile for iron-replete men). However, from 1984 to
      1994, the prevalence of iron overload (ferritin >300 microg L(-1)) increased from
      11.3% to 18.9% (P<0.0001). During the study period there was an increase in body
      mass index (P<0.0001), alcohol consumption (P<0.03) and use of non-steroid anti
      inflammatory drugs (NSAID) (P<0.0001), and a decrease in the use of vitamin
      mineral supplements (P<0.04) and in the prevalence of tobacco smoking (P<0.0001).
      In contrast, median ferritin in blood donors showed a significant fall from 1984
      to 1994 (103 vs. 74 micro g L(-1), P<0.02). CONCLUSION: Abolition of iron
      fortification reduced the iron content of the Danish diet by an average of 0.24
      mg MJ(-1), and the median dietary iron intake in men from 17 to 12 mg d(-1). From
      1984 to 1994, body iron stores and the prevalence of iron overload in Danish men
      increased significantly, despite the abolition of food iron fortification. The
      reason appears to be changes in dietary habits, with a lower consumption of dairy
      products and eggs, which inhibit iron absorption, and a higher consumption of
      alcohol, meat, and poultry, containing haem iron and enhancing iron absorption.
      The high prevalence of iron overload in men may constitute a health risk.

PMID- 12225392
TI  - Cytogenetic features of multiple myeloma: impact of gender, age, disease phase,
      culture time, and cytokine stimulation.
AB  - Relatively little is known about the cytogenetic features of multiple myeloma
      (MM) when compared to other hematologic malignancies. The reasons for this are
      most likely manifold, and include a low mitotic index of the malignant cells and
      the presence of cytogenetically cryptic abnormalities as well as of complex
      karyotypes with poor chromosome morphology. In the present study, we have
      investigated whether various culture conditions may influence the yield of
      abnormal metaphases in MM and, in the related plasma cell dyscrasias, monoclonal
      gammopathy of undetermined significance (MGUS) and plasmacytomas (PC). In
      addition, the possible impact of age, gender, and disease phase on the
      cytogenetic features has been analyzed. A total of 95 samples from 74 cases (68
      MM, three PC, and three MGUS patients) were obtained for cytogenetic analysis.
      The samples were cultured either in conventional medium or in medium containing
      IL-6 and GM-CSF, and the culture times varied from 24 to 120 h. In total, 186
      cultures were analyzed. Metaphase fluorescence in situ hybridization analysis
      using probes specific for 14q32, i.e. IGH rearrangements, could be performed in
      57 of the 74 cases, and revealed 14q32 aberrations in 10 cases not seen by
      conventional G-banding. Abnormal karyotypes were detected in 77 (41%) of the 186
      cultures, 46 (48%) of the 95 samples, and in 41 (55%) of the 74 patients,
      revealing a total of 20 chromosomal aberrations previously not reported in plasma
      cell dyscrasias. We found no evidence that gender, age, disease phase, culture
      time, or cytokine stimulation significantly influences the karyotypic features of
      MM.

PMID- 12225393
TI  - A prospective study of P-IMVP-16/CBDCA: a novel salvage chemotherapy for patients
      with aggressive non-Hodgkin's lymphoma who had previously received CHOP therapy
      as first-line chemotherapy.
AB  - The purpose of this study was to determine the efficacy of salvage chemotherapy
      with, P-IMVP-16/CBDCA, consisting of carboplatin (CBDCA), etoposide (VP-16),
      ifosfamide (IFM), and methotrexate (MTX), for patients with aggressive non
      Hodgkin's lymphoma (NHL) who had previously received CHOP [a regimen of
      cyclophosphamide, hydroxydaunomycin, Oncovin (vincristine), and prednisolone], as
      first-line chemotherapy. The 45 consecutively enrolled patients received
      methylprednisolone (mPSL) 1000 mg per body for 3 d (from day 1 to day 3), IFM
      1000 mg/m(2) for 5 d (from day 1 to day 5), MTX 30 mg/m(2) on day 3 and day 10,
      VP-16 80 mg/m(2) for 3 d (from day 1 to day 3), and CBDCA 300 mg/m(2) on day 1,
      with granulocyte colony-stimulating factor every 21 d. Patients 70 yr of age or
      older were given 75% of the standard dose. The response rate [complete response
      (CR) plus partial response (PR)] was 55.6% (25/45), including 12 (26.7%) CR and
      13 (28.9%) PR. The overall survival rate for the 45 patients was 31.1% at 1 yr
      and 17.3% at 2 yr. The failure-free survival rate for the 45 patients was 6.7% at
      1 yr and 4.4% at 2 yr. The survival rate for the 25 responders was 48.0% at 1 yr
      and 24.0% at 2 yr, and the survival rate for the 20 non-responders was 10.0% at 1
      yr (P<0.001). Multivariate analysis demonstrated that prior chemotherapy (reduced
      dose CHOP for age 70 yr or older) and the number of cases of extranodal
      involvement (>1) were significant unfavorable factors for overall survival.
      Although the major toxicity was neutropenia, no patient died of infection related
      to neutropenia. Non-hematological adverse effects were predominantly mild and
      tolerable. Unfortunately, the clinical outcome with P-IMVP-16/CBDCA was
      unfavorable, possibly because the study comprised consecutive patients who had
      received identified intensive chemotherapy, such as biweekly CHOP. Salvage
      chemotherapy with P-IMVP-16/CBDCA is not sufficient to cure relapsed or
      refractory aggressive NHL. Aggressive NHL should be cured by first-line
      chemotherapy with or without hematopoietic stem cell transplantation.

PMID- 12225394
TI  - Multiple gammac-receptor expression in adult T-cell leukemia.
AB  - Constitutive expression of the IL-2 receptor (IL-2R) on adult T-cell leukemia
      (ATL) cells and the presence of permanent IL-2-dependent ATL cell lines indicate
      that the signal transduction system via IL-2R is a key element for the
      development of this disease. IL-2R is a member of the common gamma-chain (gammac)
      receptor family and shares gamma with IL-4R, IL-7R, IL-9R, and IL-15R. In
      addition to IL-2R, ATL cells express IL-15R and respond to IL-15. In the present
      study, we examined other members of this receptor family. ATL cells showed
      various levels of IL-4Ralpha (CD124) and IL-7Ralpha (CD127) expression, and
      responded to these cytokines. In contrast, ATL cells hardly responded to IL-9. As
      primary samples were a mixed population and the results may have been modified by
      contaminating normal cells, we used ATL cell lines as pure ATL cell populations.
      Here, we report that IL-2-dependent ATL cell lines also express IL-4Ralpha and
      respond to IL-4, which was verified by the activation of cytoplasmic
      transcriptional activator Stat6 protein. Moreover, a novel ATL cell line that
      grows stably in an IL-7-dependent manner was established from one of the cell
      lines, and IL-7 induced Stat5 activation in this cell line. These results
      indicated that ATL cells have the potential to express all gammac-receptors
      except IL-9R. Overlapping and switching of cytokine receptors supported the idea
      that ATL cells can rapidly select the appropriate gammac-receptor according to
      conditions.

PMID- 12225395
TI  - Anthracyclines potentiate activity against murine leukemias L1210 and P388 in
      vivo and in vitro.
AB  - The interactions of 2-chlorodeoxyadenosine (2-CdA, cladribine) and three
      anthracyclines: doxorubicin (DOX), idarubicin (IDA) and mitoxantrone (MIT) were
      evaluated on murine leukemias P388 and L1210. Prolongation of survival time of
      animals receiving drugs in combination compared to mice treated with drugs in
      monotherapy was tested. We have also evaluated interactions of the cytostatics on
      murine leukemias in vitro by measuring their inhibitory effects on P388 and L1210
      cell proliferation. We have observed a synergistic effect of MIT and IDA in
      combination with 2-CdA on P388 leukemia resulting in an increase of life span
      (ILS)=226% in case of MIT+2-CdA and ILS=126% in the case of IDA+2-CdA, whereas 2
      CdA used as a sole drug resulted in an ILS=47%. The survival time of animals
      inoculated with P388 leukemic cells and treated with DOX+ 2-CdA was similar to
      ILS gained by DOX monotherapy (178% and 200% respectively). The mice bearing
      L1210 leukemia receiving combined chemotherapy lived significantly longer than
      the animals on single agent regimens. The animals treated with schedule 2-CdA+MIT
      lived significantly longer (P=0.004) as compared to the groups receiving drugs in
      monotherapy (ILS of 2-CdA+MIT group=60%, ILS of MIT group 33%, and 2-CdA group
      33%). Finally, combination of DOX or IDA with 2-CdA resulted in ILS =73% (2
      CdA+DOX regimen), and ILS=60% in case of 2-CdA+IDA regimen, which is
      significantly higher than ILS gained on monotherapy schedules. In vitro tests
      revealed that all tested anthracyclines enhance the antiproliferative activity of
      2-CdA against L1210 and P388 leukemic cells (P<0.05). Our study has shown that
      all anthracyclines potentiate 2-CdA antileukemic activity, both in vivo and in
      vitro. It failed however to point the best one to be combined with cladribine. We
      suggests that further clinical trials with such combinations are needed.

PMID- 12225396
TI  - Long-term follow-up of patients >or=60 yr old with acute myeloid leukaemia
      treated with intensive chemotherapy.
AB  - It is still controversial how to treat elderly patients with acute myeloid
      leukaemia (AML), and results have been poor with most regimens. We report the
      long-term results of a randomised study performed by the Leukaemia Group of
      Middle Sweden during 1984-88 comparing two intensive chemotherapeutic drug
      combinations. Ninety patients >or=60-yr old with untreated AML were randomly
      allocated to treatment with daunorubicin, cytosine arabinoside (ara-C), and
      thioguanine (TAD) (43 patients) or a combination in which aclarubicin was
      substituted for daunorubicin (TAA) (47 patients). Forty-four patients (49%)
      entered complete remission (CR), 22/43 (51%) in the TAD group and 22/47 (47%) in
      the TAA group (ns). The CR rate in patients <or=70 yr of age was 30/42 (71%) and
      in patients >70 yr 14/48 (29%) (P<0.0001). Early death within 30 d after
      treatment initiation was more often seen in patients >70 yr than in patients
      <or=70 yr of age, 40% and 12%, respectively (P<0.005). The median cause-specific
      survival time was 178 d in the total patient group, and the 2-, 5-, and 10-yr
      survivals were 22%, 11%, and 8%, respectively. The cause-specific survival was
      not significantly different between the two treatment arms. At long-term follow
      up >or=10 yr after inclusion of the last patient, 5/90 patients (one in the TAD
      group and four in the TAA group, respectively) were still alive, four in
      continuous complete remission and one in second complete remission. Thus, both
      treatment regimens appear to have similar efficacy, with a relatively high
      complete remission rate, and a reasonable survival as compared to other studies
      including some long-term survivors. However, early deaths are still numerous,
      particularly in patients above 70 yr of age, and the relapse rate is substantial.

PMID- 12225397
TI  - GM-CSF induces expression of gp91phox and stimulates retinoic acid-induced
      p47phox expression in human myeloblastic leukemia cells.
AB  - All-trans retinoic acid (ATRA) combined with granulocyte macrophage colony
      stimulating factor (GM-CSF) synergistically increases superoxide-generating
      activity in human myeloblastic leukemia ML-1 cells. ATRA is known to increase the
      expression of some NADPH components; however, little is known about the effect of
      GM-CSF on the expression of these components. We examined the expression of NADPH
      oxidase components in ML-1 cells treated with ATRA, GM-CSF, or a combination of
      ATRA and GM-CSF. Expression of p47phox and gp91phox proteins increased markedly
      after treatment with both reagents. p47phox expression was increased by ATRA
      alone, and the expression was increased synergistically by the combination of
      ATRA with GM-CSF. gp91phox was increased by ATRA or GM-CSF alone. The expression
      of p47phox and gp91phox mRNA underwent similar changes to those seen in protein
      level. These results indicate that GM-CSF induces expression of gp91phox and
      enhances ATRA-induced p47phox expression. We speculate that the remarkable
      induction of gp91phox and p47phox protein is associated with an increase in
      superoxide-generating activity due to the synergistic effect of ATRA plus GM-CSF.

PMID- 12225398
TI  - Aplastic anemia as a late complication of thymoma in remission.
AB  - Thymoma has many auto-immune associations, including aplastic anemia and
      myasthenia gravis. The pathophysiologic relationship between thymoma and its auto
      immune sequelae are yet to be fully elucidated, but are thought to be as a result
      of the production of auto-reactive T cell clones by the thymic epithelium. We
      report a case in which aplastic anemia did not develop until sometime after
      remission from thymoma had been induced. This observation suggests that auto
      reactive T cells may be produced by the thymoma but not induce clinical auto
      immune disease until a later time, even after eradication of thymoma has been
      achieved.

PMID- 12225399
TI  - Acute megakaryocytic leukemia presenting as hypercalcemia with skeletal lytic
      lesions.
AB  - Acute megakaryocytic leukemia (AML M7) is a rare type of acute myelogenous
      leukemia in adults, commonly presenting with myelofibrosis. This report describes
      a case of a 32-yr-old male who presented with hypercalcemia and bony lytic
      lesions, in the absence of myelofibrosis. The diagnosis of AML M7 should be
      considered in a patient with pancytopenia, lytic lesions and hypercalcemia.

PMID- 12225400
TI  - Acute myeloid leukaemia arising from a patient with untreated essential
      thrombocythaemia.
AB  - Acute myeloid leukaemia (AML) is an uncommon complication of patients with
      essential thrombocythaemia (ET). We report a patient with ET which progressed
      into AML and who had only received a few days of therapy with hydroxyurea (HU)
      when diagnosed with ET. This is extremely rare, as in large series no patients
      who were left untreated for their ET developed this complication. This case
      supports the theory that AML transformation can be part of the natural history of
      ET in some cases.

PMID- 12225401
TI  - Visceral leishmaniasis (kala-azar) in bone marrow aspirate.

PMID- 12225402
TI  - Abstracts of the 41st Annual Meeting of the British Society for Clinical
      Cytology. 22-24 September 2002. Cambridge, United Kingdom.

PMID- 12225405
TI  - Factors affecting thresholds in allergic contact dermatitis: safety and
      regulatory considerations.
AB  - Although it is now well understood that thresholds exist for both the induction
      and the elicitation of allergic responses, such as those of allergic contact
      dermatitis, it must also be appreciated that for any given allergen, these
      thresholds are not absolute values. They will vary between individuals, and
      according to the conditions of exposure to the allergen. Therefore, it is
      necessary for the purposes both of risk assessment and regulatory toxicology to
      appreciate the variables involved and to adopt strategies that incorporate this
      understanding. In this short article, the nature of thresholds in allergic
      contact dermatitis and the factors affecting them are reviewed. In particular,
      thresholds will vary according to whether skin exposure is transient or
      prolonged, open or occluded and single or repeated. The condition of the skin,
      the presence of inflammation and the matrix in which a chemical sensitizer comes
      into contact with the skin also are important. However, the scale of these
      variables frequently is quantifiable. Thus, recommendations can be made
      concerning how these considerations can be embraced by those responsible for
      safety evaluation and for the shaping of regulations for skin sensitizing
      chemicals/formulations.

PMID- 12225406
TI  - Clinical examinations to validate self-completion questionnaires: dermatitis in
      the UK printing industry.
AB  - A self-completion questionnaire sent to 2600 Nottinghamshire members of the
      Graphical Paper and Media Union elicited a 62% response. Forty one per cent of
      respondents reported suffering a skin complaint at some time and 11% had a
      current skin problem on the hand. This paper reports the validation stage of the
      study. Samples of 45 'cases' of self-reported dermatitis and 60 'controls', who
      reported they had never suffered a skin complaint, were clinically examined. All
      45 self-reported cases were clinically confirmed as dermatitis. Occupationally
      related irritant contact dermatitis (ICD) was diagnosed in 20 (44%); 26 (58%)
      complaints were thought to be induced or exacerbated by occupation. Of the
      controls, 21 (35%) were also diagnosed with a skin complaint, the majority being
      mild, with an occupational association in 17, the majority (15) being ICD.
      Sixteen ICD cases were patch tested resulting in positive reactions to colophony,
      neomycin, nickel and potassium dichromate (2 of each). Two cases of basal cell
      carcinoma on the face were also identified, of which the participants were
      unaware. Although there was no false positive self-reporting there was a
      considerable number of false negatives, demonstrating the importance of clinical
      validation of questionnaires relating to industrial skin disease. This study has
      highlighted the need for improvement in skin care provision in the printing
      industry.

PMID- 12225407
TI  - Do monoterpenes released from feverfew (Tanacetum parthenium) plants cause
      airborne Compositae dermatitis?
AB  - The Compositae plant feverfew (Tanacetum parthenium) is an important sensitizer
      in Europe and has been suspected of causing airborne Compositae dermatitis. A
      previous investigation of substances emitted from feverfew plants detected no
      sesquiterpene lactones, however, but mainly monoterpenes. The aims of this study
      were to test whether feverfew-allergic patients were also sensitive to some of
      the above-mentioned monoterpenes and, if so, to study associations between
      sensitization patterns, relevance of feverfew allergy and clinical features. 17
      patients with + +/+ + + reactions to feverfew and parthenolide were tested with
      15 selected monoterpenes and 2 sesquiterpenes. Of the 17 persons, 13 had positive
      and/or doubtful positive reactions to 1 or more monoterpenes. Only 1 person was
      allergic to several monoterpenes. Her history of gradually worsening Compositae
      dermatitis culminating in a probable airborne dermatitis, mimicking
      photosensitivity, and the disappearance of symptoms upon removal of feverfew
      plants suggest monoterpenes as a possible contributing factor. Similar
      associations between doubtful positive monoterpene reactions and clinical
      patterns, fragrance/colophonium allergy and relevance of feverfew allergy were
      not established with certainty. In conclusion, sensitization to the sesquiterpene
      lactones of feverfew is not invariably accompanied by sensitization to its
      volatile monoterpenes. The presence of monoterpene allergy, however, may
      contribute to airborne Compositae dermatitis.

PMID- 12225408
TI  - Contaminating resin acids have not caused the high rate of sensitivity to oak
      moss.
AB  - Commercially available oak moss absolute patch test material has recently been
      shown to contain resin acids of the type found in colophony (colophonium). We
      wished to assess whether the high frequency of positive patch tests to oak moss
      absolute at this institute was likely to reflect significant contamination by
      resin acids. The rate of positive reactions to colophony among our oak moss
      allergic patients patch tested during 1984-2000 was retrospectively investigated.
      25395 patients were tested to the European standard series during this period and
      1963 (7.7%) were allergic to the fragrance mix. 342 of these patients were
      allergic to oak moss absolute, of whom 73 (21.3%) were allergic to colophony. In
      comparison, 115 (13.4%) of 861 fragrance mix-positive but oak moss-negative
      patients were allergic to colophony (p = 0.0002, Fisher's exact test). This
      strongly statistically significant association between oak moss absolute and
      colophony shows only a small increase in rates of allergy to colophony in oak
      moss-positive patients. Thus we conclude that contaminating resin acids have not
      alone caused the high rate of sensitivity to oak moss.

PMID- 12225409
TI  - Combined effects of irritants and allergens. Synergistic effects of nickel and
      sodium lauryl sulfate in nickel- sensitized individuals.
AB  - Knowledge of the combined effects of irritants and allergens is of interest with
      respect to accurate risk assessment. The threshold for elicitation of allergic
      contact dermatitis in previously sensitized individuals may theoretically be
      markedly influenced by the simultaneous presence of irritants and allergens.
      Combined exposures have, however, only been studied infrequently. In the present
      study, the combined effect of an irritant and an allergen was evaluated in a dose
      response designed experimental study. 20 nickel-sensitized subjects were exposed
      to patch testing with varying concentrations of NiCl2 (nickel chloride) and
      sodium lauryl sulfate (SLS) alone and in combination. Evaluation of skin
      reactions was performed by colorimetry, measurement of transepidermal water loss
      and clinical evaluation, and the data were analyzed by logistic dose-response
      models. A synergistic effect was found of combined exposure to NiCl2 and SLS, as
      compared to each of the substances applied separately, as evaluated by
      colorimetry and clinical scoring. This means that the effect produced by the
      combined exposure was substantially greater than the effect produced by either of
      the substances alone. A synergistic effect of combined exposure on skin barrier
      impairment was not found, since the barrier function is significantly influenced
      by SLS-exposure only and not by NiCl2. Concentration limits are used by industry
      and government agencies to protect consumers. The present results clearly
      illustrate that elicitation thresholds and concentration limits may be influenced
      considerably by combined exposure to allergens and irritants.

PMID- 12225410
TI  - Patch test reactions to Biobans in metalworkers are often weak and not
      reproducible.
AB  - Contact allergy to the industrial preservative group of Biobans has been reported
      in individual cases. We have performed a prospective study on 408 metalworkers
      who were tested with 6 different Biobans, formaldehyde and 5 other preservatives.
      Furthermore, retesting was performed after a time interval of 6 months to 4
      years. The test results were also compared with those of the multicentric data
      provided by the Information Network of Departments of Dermatology in Germany and
      Austria (IVDK), particularly with regard to cross-reactivity between the various
      Biobans and formaldehyde. In 408 metalworkers 14 (3.4%) showed positive reactions
      to Biobans (2.2% P 1487, 2.0% CS 1246, 1.5% CS 1135), the majority being +
      reactions. On retesting 10 patients, the reactions were confirmed in only 2 cases
      (P 1487 and CS 1135). 4 patients showed positive reactions to 3 Biobans (P 1487,
      CS 1135, CS 1246), while 9 patients had only solitary sensitizations. Concomitant
      sensitization to formaldehyde was present in 5 out of 10 patients, being
      reproducible in 3 of them. In the IVDK data, sensitization prevalence in 3400
      patients ranged from 1.8% (P 1487) to 0.8% (CS 1246). A high proportion of
      doubtful or irritant reactions as well as weak + reactions was observed. Cross
      reactivity between the various Biobans was low, moderate agreement being
      calculated for CS 1135 and CS 1246 (kappa coefficient 0.43). The consensus
      pattern between formaldehyde and the tested Biobans was even lower. In
      conclusion, patch test reactions to Biobans are not rare among metalworkers but
      are often weak and not reproducible. Simultaneous reactivity to various Biobans
      and formaldehyde may be due to cross-reactivity or cosensitization from common
      exposure.

PMID- 12225411
TI  - Epidemiology of contact allergy: an estimation of morbidity employing the
      clinical epidemiology and drug-utilization research (CE-DUR) approach.
AB  - Clinical epidemiology (CE) is considered unable to estimate morbidity concerning
      either contact sensitization (CS) or allergic contact dermatitis (ACD) at the
      population level. Drug-utilization research (DUR) methods estimate the morbidity
      of suitable diseases based on prescription data for disease-specific drugs. Our
      objective was to estimate population figures for incidence and prevalence of ACD
      and CS based on sales data for patch test material in Germany and on patient data
      from the Information Network of Departments of Dermatology (IVDK). Approximately
      600000 standard series are sold per year in Germany, according to the 2 main
      manufacturers. This raw sales figure was corrected for certain effects (discarded
      preparations, proportion of formerly patch-tested patients, proportion of
      patients with ACD seeking medical advice) to obtain an estimate of the
      denominator of patients eligible for patch testing annually, and combined with
      patch test results from the Information Network of Departments of Dermatology
      (IVDK). In 17.8% (of 9266 IVDK patients) ACD was established. Extrapolated to the
      general population, an incidence of ACD of between 1.7 and 7 per 1000 per year
      was estimated, depending on whether conservative or more liberal assumptions
      concerning the above effects were made. Of 78067 IVDK patients tested between
      1992 and 2000, 46.8% had at least 1 positive reaction (+ to + + +), and 22.7% had
      at least 1 stronger positive reaction (+ + or + + +). The 9-year prevalence of CS
      was estimated to lie between 4.0% and 16.6% for the first outcome, and between
      2.0% and 8.1% for the second. Concerning single allergens, 1.9-4.5 million
      individuals are probably sensitized to nickel, and 1.4-3.4 million to fragrance
      mix among the German population of 82 million inhabitants. The morbidity data
      found in this study are in good accordance with data from population-based
      epidemiological studies. In comparison to these, the CE-DUR approach seems to be
      an economically feasible method to estimate continuously the population impact of
      ACD and CS.

PMID- 12225412
TI  - Sensitizing capacity of some trimers in p-tert-butylphenol-formaldehyde resin.
AB  - Contact allergy to p-tert-butylphenol formaldehyde resin (PTBP-F-R) is not rare.
      This resin consists of a large number of substances, most of which are still
      unknown. For diagnostic and preventive reasons the chemical identity of the
      sensitizers should be known, as well as their sensitizing capacities, cross
      reaction patterns and presence in the environment. The aims of this study were to
      investigate the sensitizing capacities and potential cross-reacting patterns for
      4-tert-butyl- 2,6-bis-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl)
      phenol (XIII), 4-tert-butyl-2- (5 - tert - butyl - 2 - hydroxy-benzyloxymethyl) -
      6 - (5 - tert - butyl - 2 - hydroxy - 3 - hydroxymethyl-benzyloxy methyl)-phenol
      (XIVa) and 7,15,23-tri-tert-butyl-25,26,27-trihydroxy-2,3,10,11,18,19-hexahomo
      3,11,19-trioxacalix(3)arene (XVIII) by the guinea pig maximization test. 4-tert
      Butyl-2,6-bis-hydroxymethyl-phenol, 4-tert-butylbenzene-1,2-diol, 4-tert-butyl-2
      hydroxymethyl-phenol, 4-tert-butyl-phenol, 4-tert-butyl-2-(5-tert-butyl-2-hydroxy
      3-hydroxymethyl-benzyloxymethyl)-6-hydroxymethyl-phenol, 4-tert-butyl-2-[5-tert
      butyl-3-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl) - 2 -hydroxy
      benzyloxymethyl] - 6 - (5 - tert-butyl- 2 -hydroxy- 3 -hydroxymethyl
      benzyloxymethyl)- phenol and were used as potential cross-reacting substances. In
      this study it is strongly indicated that the linear trimer XIII has a sensitizing
      capacity in the guinea pig which was significant when compared to the controls (p
      = 0.024). No cross-reactions were detected in animals induced with the linear
      trimer XIII. The linear trimer XIVa and the cyclic trimer XVIII failed to induce
      sensitization.

PMID- 12225413
TI  - Sensitization to clavulanic acid in Augmentin.

PMID- 12225414
TI  - Occupational contact dermatitis from a garlic and herb mixture.

PMID- 12225415
TI  - Allergic contact dermatitis from polyvinylpyrrolidone (PVP)/1-triacontene
      copolymer in a sunscreen.

PMID- 12225416
TI  - Allergic contact dermatitis caused by a mixture of sodium myristoyl sarcosinate
      and sodium myristoate in a cosmetic product.

PMID- 12225417
TI  - Oral lichen planus due to zinc in dental restorations.

PMID- 12225418
TI  - Occupational contact dermatitis from propolis.

PMID- 12225419
TI  - Photocontact dermatitis after gargling with a solution containing benzydamine.

PMID- 12225420
TI  - Contact urticaria from 2-phenoxyethanol.

PMID- 12225421
TI  - Contact dermatitis from a nickel-containing bindi.

PMID- 12225422
TI  - Contact allergy to green coffee bean dust in a coffee processing plant worker.

PMID- 12225423
TI  - Contact allergy from DMDM hydantoin, 1994-2000.

PMID- 12225424
TI  - Shoe dermatitis due to colophonium used as leather tanning or finishing agent in
      Portuguese shoes.

PMID- 12225425
TI  - Fragrance testing in the 21st century.

PMID- 12225426
TI  - Bone marrow transfusions in cadaver renal allografts: pilot trials with
      concurrent controls.
AB  - BACKGROUND: The safety and immune tolerance potential of donor marrow infusion
      with cadaveric source renal transplants was evaluated in a series of non
      randomized multicenter pilot trials by the NIH Cooperative Clinical Trials in
      Transplantation (CCTT) Group. PATIENTS AND METHODS: Three strategies were tested:
      (1) immunosuppression with cyclosporin, azathioprine and prednisone with a single
      post-transplant day 1 infusion of 5 x 107 viable cells/kg, (2) OKT3 induction
      with triple drug therapy and marrow transfusion on day 1, or (3) same therapy as
      (2) but with an additional marrow transfusion on day 10-12. RESULTS: Thirty-eight
      marrow recipients and 35 contemporaneous controls were entered with a mean follow
      up of over 5 yr. Graft survival was initially better in the marrow recipients
      than the controls but was similar after 5 yr. Microchimerism rates were similar
      for the marrow infusion and control groups throughout the follow-up period,
      regardless of the immunosuppression strategies. DISCUSSION: Bone marrow infusions
      were well tolerated by a group of cadaver renal allograft recipients. There were
      no complications from the infusion(s), no episodes of graft-vs.-host disease
      (GVHD) and no increase in infections or other complications. There was a trend
      toward early improved graft survival in marrow recipients. Decreased rejection
      rates were observed in black recipients.

PMID- 12225427
TI  - Magnesium depletion in chronic terminal liver cirrhosis.
AB  - Serum ionized magnesium represents less than 1% of the total body magnesium. The
      most reliable method to evaluate magnesium status is the magnesium loading test:
      In magnesium depletion its uptake is increased (20-50%) and is about 6% in normal
      magnesium status. There are no studies on magnesium status in chronic cirrhotics
      who may be in depletion. We performed magnesium loading test in 10 chronic
      cirrhotics listed for liver transplantation and in six healthy control patients.
      Magnesium sulphate 30 mmol was infused and urine magnesium was determined over 24
      h. Serum ionized magnesium increased similarly in all patients. The uptake of
      magnesium was 8 +/- 8% in control patients and 34 +/- 26% in cirrhotics (p <
      0.01). Chronic terminal cirrhotics are magnesium depleted which should be taken
      into account in case of liver transplantation and also in other interventions.
      Spot sampled serum ionized magnesium revealed magnesium depletion poorly.

PMID- 12225428
TI  - Report of recombinations between HLA loci within two families: utility of high
      resolution typing.
AB  - We have analysed two Caucasian families in which recombinant individuals have
      been identified. In both families, initial low resolution typing of class I and
      II antigens of possible patients referred for bone marrow transplantation and
      their respective potential donors (based on inherited haplotypes analysis)
      revealed them to be HLA identical and supposedly inheriting-non-recombinant
      haplotypes. The mothers were found to be DRB1*04 generic allele homozygous, but
      possessing two DRB1*04 specific alleles, DRB1*0403 and DRB1*0404 (family A) and
      DRB1*0401 and DRB1*0402 (family B). In both cases the patients inherited a
      maternal haplotype that is the result of a recombination event between the
      mother's HLA-DRB1 and -B genes on their chromosomes. Based on linkage
      disequilibrium it is likely that the recombinant haplotypes are present in the
      patients rather than their brothers. In both families, the results of the MLC in
      terms of relative response was positive. Thus, these cases illustrate the
      importance of high resolution DNA class II typing when assignment of MHC antigens
      is of extreme importance (i.e. bone marrow transplantation).

PMID- 12225429
TI  - Internal hernia of the small bowel around infrarenal arterial conduits after
      liver transplantation.
AB  - Internal hernia of the small bowel around infrarenal arterial conduits after
      liver Internal hernia of the small bowel is an uncommon but fatal complication of
      liver transplantation. The placement of infrarenal arterial conduits for arterial
      revascularization is an important technique for arterial reconstruction after
      liver transplantation. We report three cases of internal hernia with volvulus of
      the small bowel caused by the use of infrarenal arterial conduits. We reviewed
      the records of 1066 consecutive patients who underwent orthotopic liver
      transplantation between June 1994 and April 2000 at the University of Miami. In
      271 of these patients, grafts were revascularized by anastomosing the donor iliac
      artery to the infrarenal aorta (an infrarenal arterial conduit). Two patients
      died after the surgery. One patient died of multiple organ failure because of
      sepsis 1 month after the surgery that involved reduction of the internal hernia
      and biliary reconstruction. Another patient died of multiple organ failure
      because of sepsis 8 days after the surgery that involved reduction of the
      internal hernia and adhesiolysis. One patient survived after the surgery that
      involved thrombectomy of the arterial graft and reduction of the internal hernia.
      Although there was ischemic damage to the liver after the surgery, the patient
      recovered. However, he died of liver failure because of recurrent infection with
      the hepatitis C virus 18 months after the surgery. Transplant surgeons should be
      aware that this complication causes not only bowel obstruction but also hepatic
      arterial thrombosis and ischemic liver damage. In order to prevent this
      complication, the arterial conduit should be retroperitonealized at the time of
      transplantation.

PMID- 12225430
TI  - Psychosocial outcome of living donors after living donor liver transplantation: a
      pilot study.
AB  - In view of the scarcity of organ resources available for transplantation, living
      donor liver transplantation (LDLT) is gaining growing importance in the treatment
      of chronically terminal liver diseases. In the period between December 1999 and
      October 2000, 47 potential living liver donors were evaluated and 24 right
      hepatic lobes and two left lateral segments were transplanted at the Virchow
      Klinikum of the Charite Hospital in Berlin. The present study looks into
      biomedical and psychosocial parameters of 23 donors before and 6 months after
      LDLT. Our aims were to investigate the development of psychosocial parameters
      after donation and the relationship between psychosocial findings and post
      operative complications. Most donors showed an improved quality of life (QoL)
      after LDLT when compared with pre-operative results. Twenty-six percent of donors
      show high values for 'tiredness', 'fatigue' and 'limb pain' following donation.
      The post-operative complications had no influence on the psychosocial outcome. In
      this pilot study the resection of the right hepatic lobe amounts to a safe
      operation for donors and holds promise of a good psychosocial outcome for most
      donors, irrespective of donation-related complications. The pronounced complaints
      appears to indicate psychological tension and distress in some donors following
      donation.

PMID- 12225431
TI  - Duct-to-duct biliary reconstruction in adult-to-adult living donor liver
      transplantation.
AB  - In living donor liver transplantation (LDLT), Roux-en-Y hepaticojejunostomy has
      been a standard technique for biliary reconstruction because the majority had
      been pediatric patients with biliary atresia. Adult-to-adult LDLT using the right
      lobe graft has recently been developed and we introduced duct-to-duct biliary
      reconstruction (hepaticohepaticostomy) in such cases. The aim of this study is to
      evaluate the feasibility of this procedure in adult-to-adult LDLT. From August
      2000 to October 2001, five patients underwent adult-to-adult LDLT using the right
      hepatic lobe and were followed for more than 6 months at our institution. All
      patients underwent duct-to-duct biliary reconstruction (single
      hepaticohepaticostomy in one, multiple in four). For the grafts with multiple
      bile ducts, various techniques were used for reconstruction. In all patients,
      oral intake could be started early after the operation, and biliary leakage was
      not encountered. One patient developed two episodes of acute cholangitis who
      later developed biliary anastomosis stricture which required percutaneous
      dilatation at 11 months postop. However, otherwise, there were no infectious
      complications postoperatively. We conclude duct-to-duct biliary reconstruction is
      feasible and effective in adult-to-adult LDLT.

PMID- 12225432
TI  - De novo minimal change disease associated with reversible post-transplant
      nephrotic syndrome. A report of five cases and review of literature.
AB  - Nephrotic syndrome (NS) is frequent in renal transplant recipients and may be
      related to a large variety of glomerular lesions. In some of these cases, the
      transplant biopsy showed no significant glomerular changes and the NS was
      reversible, but the primary renal disease was not minimal change disease (MCD),
      suggesting that MCD may develop de novo in renal transplant setting. Knowledge of
      this entity, however, is limited. Among 67 cases of post-transplant NS
      encountered in a 12-yr period, five were found to be associated with de novo MCD.
      A critical review of the literature revealed nine additional cases of de novo
      MCD. The data from these 14 cases show that patients with de novo MCD had a large
      variety of primary renal diseases but MCD or focal segmental glomerulosclerosis
      was not among them. Eight of the 14 transplanted kidneys (60%) were from living
      related donors, suggesting this as a risk factor. Nephrotic range proteinuria (3
      76 g/d) developed immediately or shortly after transplantation (within 4 months
      for all reported cases, except for one at 24 months). The serum creatinine when
      NS was first diagnosed was normal or mildly elevated, but acute renal failure
      occurred in three patients. On biopsy, the glomeruli were normal or, more
      frequently, displayed mild, focal segmental mesangial sclerosis,
      hypercellularity, deposition of IgM/C3, or accumulation of mononuclear
      inflammatory cells in some glomerular capillaries. The tubulointerstitial
      compartment was normal in cases with normal renal function; displayed mild acute
      and/or chronic rejection that correlated with a mildly elevated serum creatinine;
      or showed acute changes including acute rejection, acute tubular necrosis, or
      acute cyclosporin A toxicity, which accounted for both acute renal failure at
      presentation and its subsequent reversibility. Under various treatments,
      including increased steroids, angiotensin converting enzyme inhibitors, calcium
      channel blockers and angiotensin receptor blockers, sustained remission of NS was
      achieved in 13 cases, within a year (0.5-12 months) in 10 and later (24, 34 and
      98 months, respectively) in three. In the remaining case, the patient died of
      septic shock 2 months after transplantation. After remission of the NS, the
      grafts functioned well without or with minimal proteinuria for several years. De
      novo MCD has characteristic clinical and pathologic features. It represents an
      important but hitherto underemphasized cause of post-transplant NS, which is
      potentially reversible and does not adversely affect the renal transplants.

PMID- 12225433
TI  - Role of anti-beta 2 glycoprotein 1 antibodies in ESRD patients with
      antiphospholipid antibody syndrome.
AB  - INTRODUCTION: End stage renal disorder (ESRD) patients with antiphospholipid
      antibody syndrome (APAS) are at high risk for the development of post-transplant
      renal thrombosis. Positive titre of anticardiolipin antibodies (ACA) is
      considered a major characteristic of APAS. However, several studies have
      suggested that ACA in patients with APAS do not bind to phospholipids alone. Beta
      2 glycoprotein 1 (beta 2gp1), a 40-kD plasma protein is required. In this study,
      we have tested a hypothesis that significant portions of our ESRD patients with
      APAS have antibodies only to beta 2gp1. METHODS: Serum samples from each of 169
      ESRD patients waiting for cadaver renal transplant in August 2000 were tested for
      ACA and anti-beta 2gp1 antibodies by enzyme-linked immunoabsorbent assay (ELISA)
      method. Twenty-four of these patients had clotting disorders that met the
      criteria established by the Eighth International Symposium on Antiphospholipid
      Antibodies. They included frequent arterio-venous (a-v) shunt thrombosis,
      cerebrovascular thrombosis, lupus, frequent abortions and microrenal angiopathy.
      RESULTS: Thirty-three of the patients (20%) had positive titre of either ACA or
      beta 2gp1 or both. Twenty-eight patients had ACA antibodies, of which eight had
      no evidence of clotting disorder while remaining 20 patients had various clotting
      disorders. Fourteen of these 20 patients with APAS had the positive titre of ACA
      only; the remaining six patients had both the antibodies, i.e. anti-beta 2gp1 as
      well as ACA. There were four patients with APAS that had positive titres of only
      beta 2gp1 antibodies. In total there were 11 patients with beta 2gp1 antibodies,
      10 of which had APAS, the remaining one did not. The sensitivity and the
      specificity of ACA test were 83 and 94%, respectively, and the sensitivity and
      specificity of beta 2gp1 antibody test were 71 and 99%, respectively. The chi
      square analysis demonstrated that there was statistically significant correlation
      between positive titres of both the antibodies and the presence of APAS.
      CONCLUSION: The APAS in the ESRD patients should be characterized by not only the
      positive titre of ACA but also the positive titres of anti-beta 2gp1 antibodies
      in association with history of clotting disorder.

PMID- 12225434
TI  - Renal failure after liver transplantation: outcome after calcineurin inhibitor
      withdrawal.
AB  - Chronic nephrotoxicity is one of the most serious side-effects of calcineurin
      inhibitor treatment and a factor in mortality and morbidity after liver
      transplantation. In our transplant centre, among patients who underwent a liver
      transplantation between January 1989 and December 2000, 14 liver graft recipients
      (6.86%) developed de novo severe renal dysfunction as defined by a serum
      creatinine concentration above 200 micromol/L. Renal biopsy was performed in nine
      cases and evidenced histological lesions compatible with chronic nephrotoxicity
      related to calcineurin inhibitor treatment. For nine patients, we report the
      results of a prospective non-randomized study consisting of cyclosporine or
      tacrolimus withdrawal associated with administration of mycophenolate mofetil or
      azathioprine. Despite this therapeutic modification, we did not observe a
      significant renal function improvement but on the other hand, there was no graft
      rejection.

PMID- 12225435
TI  - Effects of total body irradiation on the vascular endothelium.
AB  - Total body irradiation (TBI) is used as conditioning for stem cell
      transplantation. We studied its effects on the vascular endothelium in 55
      consecutive patients undergoing stem cell transplantation with TBI (TBI group
      n=35) or without TBI (non-TBI group: n=20). Fifty patients underwent bone marrow
      transplantation and five underwent peripheral blood stem cell transplantation.
      The levels of thrombomodulin, plasminogen activator inhibitor-1, and cyclic GMP
      were measured before and after TBI. At both times, the thrombomodulin and
      plasminogen activator inhibitor-1 levels were within the normal range in all
      patients from the two groups, without any significant differences between the
      groups. The cyclic GMP level was increased after TBI in six of 35 patients. Five
      of these six patients died as a result of complications of transplantation, while
      one patient survived in whom the cyclic GMP level rapidly returned to normal. In
      contrast, the cyclic GMP level remained normal in all patients not receiving TBI.
      These results suggest that conditioning with TBI stimulates vascular endothelial
      cells, even if it does not cause immediate direct injury. Such stimulation may be
      related to vascular endothelial dysfunction, the development of which may be
      mediated by nitric oxide.

PMID- 12225436
TI  - Two-hour post-dose cyclosporine level is a better predictor than trough level of
      acute rejection of renal allografts.
AB  - Cyclosporine (CyA) trough concentrations are poor predictors for acute rejection
      post-transplant. Patients were part of a randomized trial of basiliximab (n=70)
      vs. anti-thymocyte globulin (ATGAM) (n=65), both in combination with Neoral,
      mycophenolate mofetil, and steroids, undergoing first or second, cadaveric or
      live donor renal transplants. Whole blood samples were collected just before (C0)
      and at 2 h after CyA dosing on day 4 and at the end of weeks 1, 2, 4, and 8. The
      CyA was measured by fluorescence polarization immunoassay (TDx). Mean CyA C0 and
      C2 concentrations were calculated. Logistic regression analysis revealed that
      mean C2 level was the only predictor of acute rejection (P < or = 0.001). Higher
      mean C2 levels predicted lower rejection probabilities. Linear regression
      analysis revealed that higher mean C2 levels were not related to higher serum
      creatinine levels at either week 4 or 24 or to incidence of headache or tremor.
      The CyA C2 levels predict the frequency of rejection postrenal transplant. Target
      C2 levels are in the range of 1500 ng/dL.

PMID- 12225437
TI  - Initial report of bladder carcinoma following combined bladder-drained pancreas
      and kidney transplantation.
AB  - Although long-term survival of a functional allograft requiring long-term
      immunosuppressive therapy is responsible for higher incidence of non-urothelial
      cancers in renal allograft recipients than in normal population, the incidence of
      bladder cancer is uncommon and carcinoma of the bladder in the setting of
      combined kidney-pancreas transplantation has not been reported to date. We herein
      report a case of poorly differentiated invasive adeno-squamous cell carcinoma of
      the bladder following renal and bladder-drained pancreatic transplantation in a
      44-yr-old lady with long-standing insulin dependent diabetes mellitus, which
      necessitated radical extirpation. Management implications are reviewed.

PMID- 12225438
TI  - Enteric drainage of a pancreas allograft is safe for patients with celiac sprue.
AB  - Enteric drainage of exocrine secretions in whole organ pancreas transplantation
      is generally avoided in patients with pre-existing small bowel disease; however,
      bladder drainage is associated with a 20% rate of urinary tract-related
      complications. This is a case report of a type 1 diabetic patient with celiac
      sprue and renal failure. We performed a simultaneous cadaveric kidney pancreas
      transplant enterically draining the exocrine pancreas. There were no
      complications. The patient is now more than 6 months post-transplant with
      excellent function of both renal and pancreas allografts. We conclude that
      enteric drainage of pancreas allografts in patients with celiac sprue may be
      performed safely. Whole organ pancreas transplantation is being performed with
      greater success than ever before, mostly as a result of lessons learned from past
      experience (1). Enteric drainage of allograft exocrine secretions is preferred
      for simultaneous pancreas/kidney (SPK) recipients to avoid urinary tract
      complications associated with bladder drainage. However, most agree that
      diabetics with pre-existing bowel disease should have bladder drainage of
      allograft exocrine secretions, so as to prevent the devastating complication of a
      bowel leak. We describe here a successful case of enteric drainage of an SPK
      transplant in a patient with celiac sprue. We believe that, when carefully
      performed, enteric drainage of pancreas allografts is a safe approach for
      diabetic patients with celiac sprue, and may avert the serious complications
      associated with bladder drainage.

PMID- 12225439
TI  - "Best intentions" lives on: untoward health outcomes of some contemporary
      initiatives in Indigenous affairs.
AB  - OBJECTIVE: A shortened version of a presentation to the Australian Institute of
      Aboriginal and Torres Strait Islander Studies, this paper raises questions
      regarding policy and program directions in Indigenous affairs with consequences
      for Indigenous health. METHOD: The author notes the inadequate Indigenous mental
      health database, and describes contemporary conflicts in the arena of Indigenous
      mental health, drawing on personal experience in clinical service delivery,
      policy and programme development. RESULTS: Medicalized responses to the Stolen
      Generations report and constructions of suicide that accompanied the Royal
      Commission into Aboriginal Deaths in Custody are presented to demonstrate
      unforeseen health outcomes. Examples are also given of well-intentioned social
      interventions that, in the context of contemporary Indigenous society appear to
      be contributing to, rather than alleviating, harm. Problems of setting priorities
      that confront mental health service planners are considered in the light of past
      and continuing social disadvantage that informs the burden of mental disorder in
      Indigenous communities. CONCLUSIONS: The importance of acknowledging untoward
      outcomes of initiatives, even when motivated by concerns for social justice, is
      emphasized. The tension within mental health services of responding to the
      underpinning social issues versus providing equity in access to proven mental
      health services for Indigenous populations is considered.

PMID- 12225440
TI  - Psychiatrists as a moral community? Psychiatry under the Nazis and its
      contemporary relevance.
AB  - OBJECTIVE: In Nazi-occupied Europe, substantial numbers of psychiatrists murdered
      their patients while many other psychiatrists were complicit with their actions.
      This paper addresses their motivations and actions, and with particular reference
      to Australia, explores issues of contemporary relevance. METHODS: The events are
      reviewed in their historical context using mainly secondary sources. RESULTS: The
      assumption that the term "Nazi" denotes a closed and unrepeatable chapter is
      questioned. As with the Holocaust that followed, medical killing of psychiatric
      patients was an open secret with gradations of collective knowing. Perpetrators
      were impelled by pressure from peers and superiors, unquestioning obedience,
      racist ideology and careerism. Perpetrators and bystanders' denial was
      facilitated by use of deceptive language, bureaucratic and technical proficiency,
      and notions such as "a greater cause" or "sacred mission". Dissociation and
      numbing were common. Psychiatrists were the main medical specialty involved
      because Nazi race and eugenic ideology (accepted by many psychiatrists) targeted
      mentally ill people for sterilization and euthanasia, and because psychiatrists
      were state-controlled and tended to objectify patients. Few psychiatrists
      resisted. IMPLICATIONS: Nazi psychiatry raises questions about medical ethics,
      stigma and mental illness, scientific "fashions", psychiatry's relations with
      government, and psychiatrists' perceived core business. Psychiatric resistance to
      future similar threats should be based on commemoration, broad-based education
      and reflection on cultural values, strong partnerships between psychiatrists and
      patients, and willingness to question publicly policies and attitudes that
      disadvantage and stigmatize groups. The principle fundamental to all these
      practices is an orientation to people as subjects rather than objects.

PMID- 12225441
TI  - Project for a scientific psychiatry in the 21st century.
AB  - OBJECTIVE: To discuss potential advances in neuroscientific knowledge in the 21st
      century, enabling the realization of Freud's original vision of a basic
      biological science and an associated metapsychology. RESULTS: The Australian Twin
      Study of Attention Deficit Hyperactivity Disorder (ADHD) has demonstrated the
      high heritability of the core symptoms of ADHD, as well as showing important
      genetic and environmental influences on comorbid conditions. Brain mapping
      techniques suggest that working memory, as measured by an A-X Continuous
      Performance Task, is important in ADHD. METHODS: To outline the development of
      our own clinical research into ADHD, and the potential for future behaviour and
      molecular genetic approaches. CONCLUSIONS: The 21st century promises new and
      exciting developments in phenomenology, genetics, and neuroscientific
      understandings in Child Psychiatry.

PMID- 12225442
TI  - Mental health of adolescents in custody: the use of the "Adolescent
      Psychopathology Scale" in a Tasmanian context.
AB  - OBJECTIVE: To investigate the incidence of mental health problems based on the
      DSM-IV [1] among adolescents in custody in Tasmania, using the Adolescent
      Psychopathology Scale (APS) [2]. METHODS: The APS was administered to 50
      adolescents admitted consecutively to a youth detention centre in Tasmania,
      Australia, using a structured interview format. RESULTS: In this sample 46%
      scored positively for a mood disorder, 36% for posttraumatic stress disorder
      (PTSD), and 32% for an anxiety disorder excluding PTSD. CONCLUSIONS: Tasmania is
      no exception to the rule that adolescents in custody have a high proportion of
      mental health problems. This study confirmed findings of previous studies that
      detained adolescents had a roughly equivalent level of mental health problems as
      young people referred to mental health services and five times more than
      adolescents in the community. Therefore, all detained adolescents should be
      assessed for mental health problems as their risk is equivalent to that of young
      people referred to mental health services in the community. Youth detention
      centres are able to provide significant opportunities for individual therapy and
      group programmes for young people with mental health problems. However, to
      achieve a realization of this potential, detention facilities need to develop
      philosophies and procedures, which facilitate the development of therapeutic, as
      opposed to "punishing", environments.

PMID- 12225443
TI  - A cognitive remediation programme for adults with Attention Deficit Hyperactivity
      Disorder.
AB  - OBJECTIVE: This is the first systematic examination of the efficacy of a
      cognitive remediation programme (CRP) for management of adult Attention Deficit
      Hyperactivity Disorder (ADHD). The CRP was designed to target problems commonly
      associated with adult ADHD, namely, attention problems, poor motivation, poor
      organizational skills, impulsivity, reduced anger control and low self-esteem.
      METHOD: In a randomized, controlled trial, a representative sample of adults with
      ADHD (some medicated, some not) were assigned to either a CRP (n = 22) or a
      waiting list control (n = 21). The CRP was delivered in an intensive format with
      eight two-hour, weekly sessions with support people who acted as coaches, and
      participant workbooks with homework exercises. RESULTS: Participants who
      completed the CRP reported reduced ADHD symptomatology (effect size (d) = 1.4),
      improved organizational skills (d = 1.2) and reduced levels of anger (d = 0.5).
      Clinically significant improvements in ADHD symptomatology (d = 1.4) and
      organizational skills (d = 1.3) were maintained one year after the intervention.
      CONCLUSIONS: These findings suggest that the CRP provides a practical way of
      enhancing daily functioning for adults with ADHD.

PMID- 12225444
TI  - The Esperance primary prevention of suicide project.
AB  - BACKGROUND: Suicide has been a major community concern in Esperance, a
      geographically isolated port on the south coast of Western Australia. AIMS: To
      evaluate the effect of three evidence-based initiatives for the primary
      prevention of suicide: (i) providing suicide awareness sessions for staff members
      in health, education and social services; (ii) limiting the sale of over the
      counter analgesics (aspirin and paracetamol) to packets containing less than the
      minimum lethal dose; and (iii) implementing Commonwealth media guidelines in the
      reporting of suicides by media. METHODS: Changes in knowledge, awareness,
      attitudes, comfort and use, before and after each intervention were assessed
      using standardized instruments and pro forma derived from previous work, such as
      the Youth Suicide Prevention Training Manual and Suicide Intervention Beliefs
      Scale. Percentage changes in the number of retail outlets selling over the
      counter analgesics to less than potentially lethal quantities (less than 8 g of
      paracetamol or aspirin) were also measured. Media representatives were
      interviewed to gain their perceptions of Commonwealth Guidelines for the
      reporting of suicide, and encouraged to consult the project team before reporting
      suicide related issues. RESULTS: The baseline survey illustrated that mental
      health staff and general practitioners were more aware of suicide issues, risk
      factors for suicide and awareness of professional and ethical responses than
      staff from other services, and were more willing to raise the issue with a person
      at risk. Thirty-three subjects participated in suicide awareness training of whom
      21 (66%) returned questionnaires. There were significant increases in awareness
      of suicide-related issues and risk factors, as well as reported levels of
      knowledge of professional and ethical responses and comfort, competence and
      confidence levels when assisting a person at risk. Only three media
      representatives were aware of the Commonwealth Health Department Guidelines for
      reporting suicide and only one believed that the guidelines influenced their
      reporting. The local newspapers subsequently contacted the researchers to check
      that their reporting met the guidelines. As regards access to analgesics, one out
      of seven retailers agreed to implement the strategy (pending agreement from other
      retailers), another claimed increased awareness of the danger of analgesics, and
      three maintained that they would attempt to monitor excessive amounts sold to one
      individual. CONCLUSIONS: Local initiatives can improve the awareness and
      knowledge of staff in the assessment of suicide risk, as well as of local media.
      These need to be complemented by initiatives at State or Commonwealth level to
      produce change in statewide media, or sales of over the counter analgesics.

PMID- 12225445
TI  - Cognitive behavioural therapy combined with the relapse-prevention medication
      acamprosate: are short-term treatment outcomes for alcohol dependence improved?
AB  - OBJECTIVE: The relapse prevention medication acamprosate has been recently
      introduced to the Australian Pharmaceutical Benefits Scheme (PBS) for the
      treatment of alcohol dependence. Overseas clinical trials have demonstrated the
      efficacy of using acamprosate as an adjunct to existing psychotherapeutic
      approaches. Research has not examined treatment outcomes using a standardized
      clinical approach. The objective of this study is to investigate the impact of
      adding acamprosate to an established abstinence-based outpatient alcohol
      rehabilitation programme in an Australian population. METHODS: Fifty patients
      participated in an established 12-week, outpatient, "contract" based Cognitive
      Behavioural Therapy (CBT) alcohol abstinence programme and received acamprosate
      (CBT + acamprosate). Patients weighing > or = 60 kg were prescribed acamprosate
      calcium 333 mg tablets, two tablets three times daily (1998 mg/day) and those
      weighing < 60 kg received four tablets (1332 mg/day) daily. Outcomes were
      compared with 50 historical, matched controls, all of whom participated in the
      same program without a relapse prevention medication (CBT alone). All patients
      met DSM-IV criteria for alcohol dependence and the majority were socially
      disadvantaged. RESULTS: Programme attendance across the eight treatment sessions
      was similar in both the CBT + acamprosate and the CBT alone conditions (P =
      0.268). Relapse to alcohol use occurred sooner and more frequently in the CBT
      alone group (P = < 0.0005). Rehabilitation programme completion at 12 weeks was
      42% (CBT + acamprosate) compared with 32% for (CBT alone) (P = < 0.204). Alcohol
      abstinence at 12 weeks was 38% (CBT + acamprosate) compared with 14% (CBT alone)
      (P = < 0.006). CONCLUSION: Even within an alcohol dependent population
      characterized by poor prognostic indices, the addition of acamprosate to an
      established CBT outpatient programme significantly improved abstinence rates over
      a 12-week period. The use of acamprosate as an adjunctive treatment for alcohol
      dependence should be encouraged in Australia.

PMID- 12225446
TI  - Australian and US responses to electroconvulsive therapy dosage selection.
AB  - OBJECTIVE: The practice of electroconvulsive therapy (ECT) varies considerably
      across sites with a lack of certainty as to what constitutes seizure adequacy.
      The aim of this study was to trial a method to explore decision making and to
      describe any differences between Australian and US practitioners. METHOD: Two
      hundred and thirty-six consultant psychiatrists from Australia and US were asked
      what dosage of electrical energy they would prescribe after reading a
      standardized clinical vignette in which an unremarked upon change in seizure
      tracings followed the first two treatments. RESULTS: Considerable variability in
      the dosage was found with 17.3% decreasing, 46.8% maintaining and 30% increasing
      charge. Involvement in administration of ECT was unrelated to this decision.
      CONCLUSION: Standardized vignettes may be a useful method to assess clinicians'
      responses in dosage selection.

PMID- 12225447
TI  - Antipsychotic use in Australia: the patients' perspective.
AB  - OBJECTIVE: To describe patterns of self-reported medication use in a population
      based sample of people with psychotic disorders; to establish correlates with
      clinical variables; to determine perceived side-effect burden; and investigate
      patient perception of efficacy for different classes of antipsychotic agent.
      METHODS: Using the Australian Low Prevalence (Psychosis) Study database we
      analysed patterns of psychotropic medication and examined their clinical
      correlates. We also determined rates of reported side-effects and perceived
      benefit or otherwise associated with the different antipsychotic drugs. RESULTS:
      Of the 1126 persons interviewed, 88.6% were on psychotropic medication; 54.3%
      were using "typical" antipsychotics (24.8% in depot form), while 8.3% were on
      clozapine, 13.3% on risperidone, and 8.8% on olanzapine. Around 30% of women, and
      20% of men, were on mood stabilizers or antidepressants. Over half of respondents
      were on more than one agent. Of those on only one agent, nearly 80% reported at
      least one side-effect; the mean number of side-effects was 3.9 for typical
      antipsychotics, and 3.3 for atypicals. Atypicals, notably clozapine, tended to be
      rated by patients as more efficacious than typicals; depot preparations, in
      particular, tended to be seen as unhelpful, and were associated with a higher
      side-effect burden. CONCLUSIONS: This study presents an insight into patients'
      perception of efficacy and side-effects of antipsychotic medications. The
      findings have implications for clinicians, and can inform treatment options in
      people with psychotic disorders.

PMID- 12225448
TI  - Pro re nata medication for psychoses: the knowledge and beliefs of doctors and
      nurses.
AB  - OBJECTIVE: To examine the knowledge and beliefs of doctors and nurses in
      inpatient psychiatric units about pro re nata (PRN) (as needed) medications for
      psychotic disorders. METHODS: Medical (n = 44) and nursing (n = 80) staff in two
      metropolitan public hospital units completed a structured questionnaire about
      their use of PRN psychotropic medications on one occasion during the four months
      from March-June 1999. RESULTS: Nurses selected more indications for PRN
      antipsychotics than doctors (3.49 vs 2.72, p < 0.05), whereas doctors selected
      more indications for PRN benzodiazepines (3.77 vs 3.19, p < 0.05). The groups did
      not differ in the number of selected indications for using anticholinergics. For
      agitation, the majority of nurses viewed both benzodiazepines (56%) and
      antipsychotics (86%) as effective, with 60% preferring an antipsychotic. For the
      acute control of psychotic symptoms, 99% of nurses believed antipsychotics were
      effective and 58% benzodiazepines, with 87% preferring an antipsychotic. A large
      majority of doctors viewed both PRN benzodiazepines, 94%,and antipsychotics, 81%,
      as effective for agitation, and 55% preferred to use a benzodiazepine. For
      psychotic symptoms, 80% believed PRN antipsychotics were effective, but only 32%
      viewed benzodiazepines as effective, and 64% preferred to use an antipsychotic.
      Nursing staff identified more non-pharmacological techniques for managing both
      agitation and psychotic symptoms and reported using these more often than
      doctors. Junior staff, both nursing and medical, had less knowledge of non
      pharmacological alternatives to PRN medication than senior staff. CONCLUSIONS:
      Disparities existed between doctors and nurses views on the indications for PRN
      medication in the acute management of psychoses, thus it is important for doctors
      to specify indications when writing PRN prescriptions. Despite evidence for the
      safety and effectiveness of benzodiazepines, there was widespread reluctance to
      use them as PRN medication in acute psychoses. Beliefs of some staff about PRN
      medications were at odds with the known properties of these medicines.
      Educational interventions for both nurses and doctors are required to achieve
      best practice in PRN medication.

PMID- 12225449
TI  - Pro re nata medication for psychoses: an audit of practice in two metropolitan
      hospitals.
AB  - OBJECTIVE: To examine the use of pro re nata (PRN) (as needed) medication in
      hospitalized patients with psychotic disorders. METHODS: Retrospective chart
      reviews were conducted at two large public psychiatry units situated in inner
      city general hospitals. Pro re nata medication prescription, administration and
      outcomes were examined during inpatient episodes of care for 184 consecutive
      admissions of patients diagnosed with a psychotic disorder. Patient demographics,
      diagnoses, and regularly prescribed medication were also recorded. All admissions
      were drawn from a three-month period from December 1998-February 1999. RESULTS:
      The most prevalent diagnoses were schizophrenia related disorders (n = 111) and
      mania (n = 34). Substance use disorders (n = 49) were the most common comorbid
      dis-orders. Pro re nata medication was administered during the acute phase of 82%
      of admissions. Drugs prescribed Pro re nata were mostly typical antipsychotics,
      benzodiazepines and/or anti-cholinergics. Coprescription of typical
      antipsychotics PRN with regularly scheduled atypical antipsychotics was common
      (64%). Pro re nata medications accounted for 31% of the total antipsychotic dose
      and 28% of the total anxiolytic dose administered during acute treatment. Higher
      daily doses of PRN medication were given to manic patients, males, younger
      patients and those with substance use disorders. Pro re nata prescriptions
      usually specified a maximum daily dose (87%) but rarely gave indications for use
      (6%). Administration records frequently lacked a specified reason for use (48%)
      or a notation of outcome (64%). Unit staff noted medication-related morbidity in
      37% of patients receiving PRN medication, compared to 3% of patients receiving
      only regularly scheduled medication. Extrapyramidal symptoms (EPS) were most
      frequently associated with administration of PRN haloperidol (Relative Risk vs
      other PRN medications = 5.61, 95% CI = 2.36-13.73). CONCLUSIONS: Pro re nata
      medications comprised a significant part of the treatment which psychotic
      patients received. The common practice of coprescribing PRN typical
      antipsychotics with scheduled atypical antipsychotics is potentially
      problematical since administration of PRN medication is associated with
      significant medication related morbidity. Preferential use of benzodiazepines as
      PRN agents may minimize this morbidity and foster subsequent compliance with
      regularly prescribed antipsychotics.

PMID- 12225450
TI  - The neurobehavioural effects of kava.
AB  - OBJECTIVE: This review considers the context in which kava is used, together with
      its underlying psychopharmacological mechanisms, to investigate the
      neurobehavioural effects associated with kava use. METHOD: We conducted a
      systematic search using the computerized databases MEDLINE, OVID and PsychLIT for
      all articles containing any of the following words: kava, kavain, kawa and Piper
      methysticum. In the opinion of the authors, all articles from this collection
      containing data that could inform the neurological and cognitive sequelae of kava
      use were included for the purpose of this review. RESULTS: The use of kava occurs
      among indigenous populations in the South Pacific and in northern Australia,
      while also being used throughout the western world as a herbal medicine. Animal
      studies show that kava lactones alter neuronal excitation through direct
      interactions with voltage-dependent ion channels, giving rise to kava's muscle
      relaxant, anaesthetic, anxiolytic and anticonvulsive properties. Several isolated
      cases of psychotic and severe dystonic reactions following kava use suggest that
      kava also has psychoactive properties, yet there is no conclusive evidence that
      kava interferes with normal cognitive processes. CONCLUSIONS: Kava is effective
      in the treatment of tension and anxiety. There may be risk-factors for severe
      motor and psychiatric responses to kava use, although these are not well
      understood. Given the increasingly widespread use of kava, further investigation
      is necessary to gain an understanding of its immediate neuropsychiatric effects
      and long-term cognitive effects.

PMID- 12225451
TI  - Maternal bonding behaviour in schizophrenia and schizoaffective disorder,
      considering premorbid personality traits.
AB  - OBJECTIVE: Bonding between mother and child is described as a complex two-way
      process ensuring the needs of the child for nurture and protection. As such, it
      is dependent on the contribution of mother and child [1-3] whereby
      characteristics of personality of the child may have consequences on maternal
      bonding behaviour. In the current study the perception of maternal behaviour,
      premorbid personality traits and relationships between maternal behaviour and
      personality traits were investigated in schizophrenic and schizoaffective
      patients and their same-sex, healthy siblings. METHODS: We recruited 36
      schizophrenic and schizoaffective patients and their same-sex healthy siblings.
      Information about maternal bonding behaviour was assessed by the Parental Bonding
      Instrument, information about premorbid personality traits was obtained from
      their mothers using the "Giessen-Test". RESULTS: Compared to their siblings,
      patients showed less social resonance, more permeability, less social competence
      and a more depressed and anxious mood. Furthermore, patients described their
      mothers to be less caring and to be more overprotective than their siblings
      described them. But there were strong associations between maternal bonding
      behaviour and premorbid personality traits. These findings were supported by
      missing significant differences in maternal care behaviour between patients and
      siblings when using premorbid characteristics as covariates. Significant high
      maternal overprotection perceived by patients with schizophrenia and
      schizoaffective disorders still remained after correcting for the influence of
      premorbid personality traits. CONCLUSION: The results suggest that premorbid
      personality traits should be considered not only in analyses of maternal care
      behaviour in schizophrenic and schizoaffective patients but also when studying
      other psychiatric patient groups.

PMID- 12225452
TI  - Cortical excitability of psychiatric disorders: reduced post-exercise
      facilitation in depression compared to schizophrenia and controls.
AB  - OBJECTIVE: In normal subjects, motor evoked potentials (MEPs) produced by
      transcranial magnetic stimulation (TMS) from the motor cortex are increased after
      non-fatiguing exercise of hand muscles. This phenomenon is called post-exercise
      facilitation. This study aims to test the hypothesis that psychiatric syndromes
      (major depressive episode, schizophrenia) have different levels of post-exercise
      facilitation compared to controls. METHODS: Patients with DSM-IV major depressive
      episode (six female, four male), schizophrenia (two female, nine male) and a
      control group (nine female, four male) participated. MEPs were elicited pre- and
      post-exercise from the contralateral abductor pollicis brevis by TMS over the
      primary motor cortex. RESULTS: Post-exercise facilitation expressed as a
      percentage of baseline was 510% in controls, 110% in depression and 190% in
      schizophrenia. There were significant differences in patients with depression and
      schizophrenia compared to controls (p = 0.0001, p = 0.0008). CONCLUSIONS: Post
      exercise facilitation was reduced in depression and schizophrenia, suggesting
      impaired cortical excitability in these disorders. Further studies may
      discriminate between the two groups.

PMID- 12225453
TI  - The mental health status of Filipinas in Queensland.
AB  - OBJECTIVE: To determine the prevalence and investigate potential predictors of
      psychological distress in Filipino women living in Queensland, Australia.
      METHODS: The sample of n = 487 women (88% response rate) was drawn from Filipino
      organization membership lists and supplemented by snowball sampling. Participants
      were interviewed in their homes or at a community event in 1996/1997. Follow-up
      in 1997/1998 involved n = 346 women (71% response rate) who were interviewed
      either in their homes or by telephone. The two surveys included measurement of
      demographic, immigration, physical health, satisfaction with life in Australia
      and life event variables. The GHQ-28 was included in the follow-up survey as a
      measure of psychological distress. RESULTS: The proportion of women having an
      above threshold score (using the cut-off of 4/5) on the GHQ-28 was 23%. Women who
      were single, dissatisfied with life in Australia, had reported a major change in
      their financial situation, their relationship or their health in the year between
      surveys were significantly more likely to have an above threshold score.
      CONCLUSIONS: The level of mental distress among Filipinas in Queensland appears
      to be slightly higher than the levels reported in the general population but
      lower than other migrant groups. The determinants of mental distress in this
      population contrast with those in the general Australian population and other
      migrant groups. The social context of these determinants in Filipinas needs to be
      elicited for an understanding of these differences.

PMID- 12225454
TI  - The social and cultural context of the mental health of Filipinas in Queensland.
AB  - OBJECTIVE: To describe the social and cultural context of risk surrounding the
      mental health of Filipino women living in Queensland, Australia and elicit the
      meaning and experience of mental health and illness for these women. METHODS: One
      hundred and thirty-nine in-depth interviews and 7 focus group discussions (FGDs)
      were nested within the baseline survey of the Filipina cohort of the Australian
      Longitudinal Study on Women's Health. Seventy-four in-depth interviews and 8 FGDs
      were conducted at follow-up. A semi-structured interview guide that included
      sections on emotional health, social support and changes guided these. A subset
      of responses was fully transcribed and analysed for ethnographic content and
      themes. RESULTS: "Mental" problems are highly stigmatized, in comparison to
      "emotional" problems that are believed to result largely from the absence of
      close family ties. The loss of these ties and the transition from a collectivist
      to individualist society are key themes related to emotional distress in
      Filipinas. CONCLUSIONS: This understanding of meaning and context of mental
      health and its risk factors in migrants is important for informing public health
      and clinical practice and for the improvement of quantitative research
      instruments.

PMID- 12225455
TI  - Rural-urban differences in reasons for living.
AB  - OBJECTIVE: The suicide rate in Australia is cause for concern, especially the
      increase in attempted and completed suicides in rural and regional locations. The
      present study examined reasons for choosing not to commit suicide as a function
      of residential location. METHOD: The study involved 655 Victorian residents from
      four population-based strata; urban, regional city, regional town, and rural.
      RESULTS: Results from the Reasons for Living Inventory revealed significant
      differences as a function of residential location. Overall, residents in rural
      locations reported having significantly more to live for than their urban
      counterparts. Further analysis of six reasons for living (child, family, moral,
      social, coping and death-related concerns) showed a pattern whereby residents in
      rural locations reported having the most to live for, followed by regional
      residents, and urban residents who reported having the least to live for.
      CONCLUSIONS: These findings are in contrast to increase of suicide rates in rural
      areas, and highlight the need for a greater understanding of the mechanisms
      underlying suicidal behaviour.

PMID- 12225456
TI  - A profile of regional psychiatry publishing: home and away.
AB  - OBJECTIVE: Previous reports have profiled Australian psychiatry publishing in
      high-ranking international journals over the last two decades. An audit of
      selected high ranking and regional psychiatric journals was therefore undertaken
      to obtain a current profile of Australasian publishing. METHODS: Journals were
      selected on the basis of impact factors for the year 2000, with the top five
      regional, generalist and specialist journals being selected, and with publication
      numbers over a two-year period (1999-2000) compared with numbers from other major
      geographical regions. RESULTS: Of the 4573 papers identified in the 15 journals,
      Australasian authors contributed 269 to the regional journals (with two-thirds in
      the Australian and New Zealand Journal of Psychiatry), 47 to the generalist
      journals (with two-thirds in Psychological Medicine) and very few (23) to the
      specialist journals. Representation in the so-called "dominant four"
      international journals has increased since the 1986-1989 audit. When analysis was
      made of the "top nine" international journals, the Australasian representation
      rate was a low 1.8% and lower than most regions examined. CONCLUSIONS: If
      Australasian psychiatry is to advance its international presence, a greater
      representation rate in top-ranking international journals should be set as an
      objective.

PMID- 12225457
TI  - Depictions of mental illness in print media: a prospective national sample.
AB  - OBJECTIVE: Because there are no published reports of depictions of mental illness
      in print media based on national samples, we set out to prospectively collect and
      analyse a near complete New Zealand sample of print media. METHODS: A commercial
      clipping bureau was contracted to provide cuttings of all items with any mental
      health or illness aspect over a four week period. These items were analysed for
      potentially positive and negative depictions and how mental illness was
      represented within each item. An independent search for additional newspaper
      items concerning one prominently featured topic indicated that the rate of
      identification of relevant stories was at least 91%. RESULT: The collection
      consisted of six hundred print items which were most commonly news or editorial
      pieces (n = 562, 93.7%). Negative depictions predominated, with dangerousness to
      others (n = 368, 61.3%) and criminality (n = 284, 47.3%) being the most common.
      Positive depictions, including human rights themes, leadership and educational
      accomplishments occurred in 27% (n = 164) of all items. Generic mental illness
      terminology without reference to specific diagnostic categories was present in
      47% of all items (n = 284). CONCLUSIONS: Negative depictions that predominate
      confirm the stereotypic understanding of mental illness that is stigmatizing.
      These findings underscore the challenge facing us as mental health professionals
      attempting to change attitudes towards mental disorders when the stereotypes are
      so regularly reinforced.

PMID- 12225458
TI  - The myth of the biopsychosocial model.

PMID- 12225459
TI  - A UK perspective of case management.

PMID- 12225461
TI  - Comments on lithium toxicity.

PMID- 12225463
TI  - Cardiac risk of psychotropic drugs.

PMID- 12225464
TI  - Dermatoglyphics and schizophrenia: a Mexican study.

PMID- 12225473
TI  - MR imaging of cranial nerve lesions using six different high-resolution T1- and
      T2(*)-weighted 3D and 2D sequences.
AB  - PURPOSE: To find a suitable high-resolution MR protocol for the visualization of
      lesions of all 12 cranial nerves. MATERIAL AND METHODS: Thirty-eight
      pathologically changed cranial nerves (17 patients) were studied with MR imaging
      at 1.5 T using 3D T2*-weighted CISS, T1-weighted 3D MP-RAGE (without and with
      i.v. contrast medium), T2-weighted 3D TSE, T2-weighted 2D TSE and T1-weighted fat
      saturation 2D TSE sequences. Visibility of the 38 lesions of the 12 cranial
      nerves in each sequence was evaluated by consensus of two radiologists using an
      evaluation scale from 1 (excellently visible) to 4 (not visible). RESULTS: The 3D
      CISS sequence provided the best resolution of the cranial nerves and their
      lesions when surrounded by CSF. In nerves which were not surrounded by CSF, the
      2D T1-weighted contrast-enhanced fat suppression technique was the best sequence.
      CONCLUSIONS: A combination of 3D CISS, the 2D T1-weighted fat suppressed sequence
      and a 3D contrast-enhanced MP-RAGE proved to be the most useful sequence to
      visualize all lesions of the cranial nerves. For the determination of
      enhancement, an additional 3D MP-RAGE sequence without contrast medium is
      required. This sequence is also very sensitive for the detection of hemorrhage.

PMID- 12225474
TI  - Dynamic susceptibility contrast-enhanced echo-planar imaging of cerebral gliomas.
      Effect of contrast medium extravasation.
AB  - PURPOSE: To assess the influence of the degree of contrast medium extravasation
      on different DSC EPI MR sequences for perfusion MR imaging. MATERIAL AND METHODS:
      60 patients with cerebral gliomas were examined by either an FID EPI or an SE EPI
      DSC MR sequence. The acquired images were evaluated on a qualitative and
      quantitative basis. For qualitative assessment, the homogeneity of the signal
      time curve, image artifacts, the degree of signal drop and the degree of
      enhancement were evaluated. The quantitative assessment included the percentage
      of signal drop and the contrast-to-noise ratio of the different EPI sequences was
      analyzed. RESULTS: FID EPI presented a more homogeneous signal time curve and a
      more pronounced susceptibility effect than the SE EPI sequence. Due to the lesser
      susceptibility effect, the SE EPI sequence was not as sensitive to contrast media
      extravasation. The signal returned to baseline in all patients. In patients with
      strongly enhancing lesions, the FID EPI sequence suffered from considerable T1
      effects, causing problems in the quantification of perfusion data. CONCLUSION:
      FID EPI sequences were preferred for perfusion MR imaging in patients without
      strong enhancing lesions, e.g. in ischemia or tumors with intact blood-brain
      barrier. In patients with suspected strong enhancing lesions, an SE EPI sequence
      should be used.

PMID- 12225475
TI  - Reliability of perfusion MR imaging in symptomatic carotid occlusive disease.
      Cerebral blood volume, mean transit time and time-to-peak.
AB  - PURPOSE: Perfusion MR imaging offers an easy quantitative evaluation of relative
      regional cerebral blood volume (rrCBV), relative mean transit time (rMTT) and
      time-to-peak (TTP). The purpose of this study was to investigate the reliability
      of these parameters in assessing the hemodynamic disturbance of carotid occlusive
      disease in comparison with normative data. MATERIAL AND METHODS: Dynamic contrast
      enhanced T2*-weighted perfusion MR imaging was performed in 19 patients with
      symptomatic unilateral internal carotid artery occlusion and 20 control subjects.
      The three parameters were calculated from the concentration-time curve fitted by
      gamma-variate function. Lesion-to-contralateral ratios of each parameter were
      compared between patients and control subjects. RESULTS: Mean +/- SD of rrCBV,
      rMTT and TTP ratios of patients were 1.089 +/- 0.118, 1.054 +/- 0.031 and 1.062
      +/- 0.039, respectively, and those of control subjects were 1.002 +/- 0.045,
      1.000 +/- 0.006, 1.001 +/- 0.006, respectively. The rMTT and TTP ratios of all
      patients were greater than 2 SDs of control data, whereas in only 6 patients
      (32%), rrCBV ratios were greater than 2 SDs of control data. The three parameter
      ratios of the patients were significantly high compared with those of control
      subjects, respectively (p < 0.01 for rrCBV ratios, p < 0.0001 for rMTT ratios,
      and p < 0.0001 for TTP ratios). CONCLUSION: Our results indicate that rMTT and
      TTP of patients, in contrast to rrCBV, are distributed in narrow ranges minimally
      overlapped with control data. The rMTT and TTP could be more reliable parameters
      than rrCBV in assessing the hemodynamic disturbance in carotid occlusive disease.

PMID- 12225476
TI  - Comparative evaluation of cerebral blood volume and cerebral blood flow in acute
      ischemic stroke by using perfusion-weighted MR imaging and SPECT.
AB  - PURPOSE: To investigate the relationship between relative cerebral blood volume
      (CBV) measured with perfusion-weighted (PW) MR imaging and relative cerebral
      blood flow (CBF) measured with SPECT in acute ischemic stroke. MATERIAL AND
      METHODS: Fifteen patients who had acute unilateral middle cerebral artery
      occlusion underwent both PW MR imaging and 99mTc-HMPAO SPECT with an interval
      less than 20 min between the two examinations within 6 h after stroke onset.
      Lesion-to-contralateral relative CBV and CBF ratios measured in multiple regions
      of interest were compared to evaluate the relationship of the two parameters.
      RESULTS: An overall linear relationship was found between relative CBV and
      relative CBF ratios (R2 = 0.54, p < 0.0001). The two parameters correlated
      linearly to each other in regions with evolving infarction (R2 = 0.43, p<0.0001),
      but not in regions without evolving infarction (R2 = 0.001, p>0.05). Regions with
      evolving infarction had more severe hypoperfusion (mean relative CBF ratio, 0.38
      +/- 0.22) than regions without (mean relative CBF ratio, 0.70+/-0.13) (p<0.0001).
      CONCLUSION: A significant linear relationship existed between relative CBV and
      relative CBF in acute ischemic stroke, although relative CBV did not change
      linearly to relative CBF in mild hypoperfusion. Relative CBV can be used as an
      alternative to relative CBF within 6 h after stroke onset, particularly in
      regions with severe hypoperfusion proceeding to infarction.

PMID- 12225477
TI  - Subcutaneous chest ports via the internal jugular vein. A retrospective study of
      117 oncology patients.
AB  - PURPOSE: To review image-guided chest port insertion using the right internal
      jugular vein as the access site of choice. MATERIAL AND METHODS: One hundred and
      eighteen subcutaneous chest ports were placed via the internal jugular vein in
      117 patients with malignancies using both fluoroscopic and US guidance in
      interventional radiology suites. RESULTS: The technical success rate was 100%
      with no procedural complications. Follow-up was obtained in all patients with
      total access days of 40,450 days (mean, 342.8 days). Premature catheter removal
      was required in 8 patients (6.8%, 0.20 per 1,000 access days) due to non
      treatable complications: 2 catheter occlusions/malfunctions (1.7%, 0.05 per 1,000
      access days), 1 catheter-related skin erosion (0.85%, 0.024 per 1,000 access
      days), and 5 infections (4.2%, 0.15 per 1,000 access days). Two symptomatic right
      upper extremity venous thromboses also occurred (1.7%, 0.05 per 1,000 access
      days) that were treated successfully with anticoagulation. CONCLUSION: Image
      guided placement of internal jugular vein chest ports has a high success rate and
      low complication rate compared with reported series of unguided subclavian vein
      port insertion. The internal jugular vein should be used as the preferred venous
      access site compared to the subclavian vein.

PMID- 12225478
TI  - Contrast enhancement of round atelectases.
AB  - PURPOSE: To find out if round atelectases (RAs) of a lung enhance more than
      pulmonary malignant tumors. MATERIAL AND METHODS: Twelve patients with RA and 16
      patients with malignant lung tumor (MLT) evidenced on CT examination were
      selected (14 RAs and 16 MLTs). Two patients had 2 RAs. The examination data were
      reviewed on a work station and the attenuation values of RAs and tumors were
      measured. RESULTS: At enhanced CT the density of RAs varied from 88 to 190 HU
      whereas for MLTs the density varied from 30 to 71 HU. The difference between
      attenuation values of RAs and MLTs was statistically significant. CONCLUSION: The
      attenuation values of RAs after contrast enhancement seem to differ from those of
      MLTs, at least during the first minute after contrast injection, and thus serve
      as a useful aid in the differential diagnosis of these masses.

PMID- 12225479
TI  - Thymic lesions and myasthenia gravis. Diagnosis based on mediastinal imaging and
      pathological findings.
AB  - PURPOSE: To achieve a better understanding of the role of CT and MR imaging in
      the study of the mediastinum in patients with myasthenia gravis (MG). MATERIAL
      AND METHODS: Mediastinal CT and MR findings were correlated with the
      histopathological results in 104 thymectomized MG patients. RESULTS: CT was
      performed in 104 patients; in 11 of them, MR was also carried out. 44 patients
      had hyperplasia at histology. On CT, thymic hyperplasia was confirmed in 16
      cases, thymoma was diagnosed in 10 and a normal thymus in 18 (sensitivity 36%,
      specificity 95%). Of 52 patients with thymoma at histology, CT showed thymoma in
      46, hyperplasia in 1, and normal thymus in 5. CT showed 88.5% sensitivity and 77%
      specificity for thymoma. In 10 patients with invasive thymoma, CT was
      indiscriminate, while invasiveness was detected in 7 cases at MR (70%
      sensitivity) and at CT in 1 case. Both CT and MR detected tumor recurrence in 5
      cases, but the exact localization and degree of invasion were best defined by MR.
      CONCLUSION: In MG patients CT is a sensitive, specific and efficient modality for
      detecting thymoma, but is less so for detecting thymic hyperplasia. MR was shown
      to be accurate in detecting invasive thymoma both preoperatively and in
      postoperative follow-up.

PMID- 12225480
TI  - Comparison between high-resolution helical CT and pathology in breast
      examination.
AB  - PURPOSE: To determine whether high-resolution helical CT can show the
      architectural features of breast carcinomas of non-limited extent (non-BCLE) and
      to establish the CT characteristic morphology of non-BCLE. MATERIAL AND METHODS:
      We prospectively studied high-resolution helical CT of 136 invasive breast
      carcinomas before breast-conserving surgery. Non-BCLE were defined as ductal
      carcinomas in situ and invasive carcinomas beyond 1 cm from the edge of the
      dominant mass. Non-BCLE were defined as positive if enhanced beyond 1 cm from the
      edge of the focal enhancement on CT. After surgical resection, specimens were
      sliced in serial sections at 5-mm intervals, and the gross morphology and
      histology were correlated with the appearance of the preoperative CT lesion
      images. RESULTS: Non-BCLE were present in 47 invasive carcinomas. The sensitivity
      and specificity of non-BCLE evaluation by high-resolution helical CT were 70% and
      89%, respectively. The morphology of non-BCLE on CT agreed with histologic
      findings. The morphological pattern on CT significantly correlated with
      intraductal tumor density adjacent to invasive tumor. CONCLUSION: Comparison of
      high-resolution helical CT with histologic data suggests that demonstration of a
      non-BCLE morphology can make the CT breast carcinoma local staging more accurate.

PMID- 12225481
TI  - Selection of patients with infrainguinal arterial occlusive disease for
      percutaneous transluminal angioplasty with duplex scanning.
AB  - AIM: To evaluate the role of duplex scanning in the selection of patients with
      infrainguinal arterial occlusive disease for percutaneous transluminal
      angioplasty (PTA). MATERIAL AND METHODS: From January 1995 through May 2000, 702
      patients (952 limbs), with chronic lower extremity ischemia due to infrainguinal
      atherosclerotic disease diagnosed by duplex scanning, were retrospectively
      studied. Diagnostic angiography (130 limbs) or infrainguinal PTA (108 limbs) was
      performed in 238 limbs. Two investigators retrospectively analyzed the duplex
      examinations and angiographies in a blinded manner and used similar criteria for
      the interpretation of lesions suitable or not suitable for PTA. RESULTS: The
      superficial femoral, popliteal and crural artery lesions were correctly selected
      for PTA in 85%, 66% and 32%, respectively. The accuracy, sensitivity,
      specificity, negative predictive value and positive predictive value of duplex
      scanning to appropriately categorize femoropopliteal lesions as suitable or
      unsuitable for PTA were 89%, 83%, 92%, 94% and 78%, respectively. The accuracy of
      duplex scanning for predicting the performance of infrainguinal PTA was 83%.
      CONCLUSION: Duplex scanning has an important impact on the selection of treatment
      modalities in limbs with infrainguinal arterial occlusive disease.
      Femoropopliteal lesions can be reliably selected to PTA according to duplex scan
      findings.

PMID- 12225482
TI  - Treatment of femoral pseudoaneurysms. Percutaneous US-guided thrombin injection
      versus US-guided compression.
AB  - PURPOSE: Thrombin injection in femoral pseudoaneurysms has been suggested to be
      superior to traditional US-guided compression. Our aim was to evaluate results
      with compression therapy with special reference to use of thrombin in case of
      failure. We also studied 7 patients who underwent primary thrombin injection.
      MATERIAL AND METHODS: We retrospectively reviewed all (n=44) femoral artery
      pseudoaneurysms diagnosed at our department during October 1998-May 1999. US
      guided compression with the Femostop device or US-guided thrombin injection (100
      1000 IU) was the first choice according to the physicians' preference, followed
      by the other regime if the first choice was non-successful. RESULTS: Thirty-nine
      (89%) of the patients received anticoagulation treatment and/or concomitant
      antiplatelet drugs. Out of the 44 patients, 37 were treated with compression as
      the first choice. This regime was successful in 22 (59%). This group included 2
      lesions that resolved spontaneously after initially failed compression and 1 deep
      venous thrombosis after treatment. The persistent 15 pseudoaneurysms after failed
      compression received thrombin injection, and it was also the primary therapy in 7
      patients. Complete thrombosis within the pseudoaneurysm was immediately induced
      after treatment. One early recurrence required a second injection. No
      complication of thrombin was noted and no surgery was required. CONCLUSION: US
      guided thrombin injection is an effective treatment for embolisation of
      pseudoaneurysms. The technique is superior to compression therapy.

PMID- 12225483
TI  - On the appearance of bile in clinical MR cholangiopancreatography.
AB  - PURPOSE: To study the appearance of bile in clinical MR cholangiopancreatography
      (MRCP) with special reference to its chemical and physical properties. MATERIAL
      AND METHODS: Gallbladder bile was collected during surgery from 38 patients and
      studied with respect to chemical constituents. The relaxation rates 1/T1 and 1/T2
      of bile were also determined in vitro. In 16 of these 38 patients, abdominal
      imaging was performed using MRCP as well as T1-weighted GE sequences. RESULTS:
      For 9 of the 13 chemical parameters studied, a positive significant correlation
      with 1/T1 as well as 1/T2 was found. The median relaxation rates 1/T1 and 1/T2
      were 0.76 and 1.48 s-1, respectively. The corresponding ranges were 0.38-3.13 s-1
      and 0.70-5.75 s-1, respectively. On the MRCP images a few patients showed
      gallbladder of poor visibility due to low signal-to-noise ratio. This coincided
      with a high relaxation rate 1/T2 of bile. On the T1-weighted GE sequences a few
      patients showed hyperintense gallbladder relative to liver, coinciding with high
      relaxation rates 1/T1 of bile. CONCLUSION: Bile was found to show a large
      interindividual variation with respect to relaxation rates 1/T1 and 1/T2. The
      relaxation rates increased with increasing amounts of substances in the bile. For
      some patients (11%) MRCP imaging is unsuccessful due to high relaxation rate of
      bile.

PMID- 12225484
TI  - Intravenous contrast-enhanced Doppler sonography and intra-arterial carbon
      dioxide-enhanced sonography in the assessment of hepatocellular carcinoma
      vascularity before and after treatment.
AB  - PURPOSE: To compare i.v. contrast-enhanced sonography (CEUS), power Doppler
      sonography (PDUS) and i.a. carbon dioxide-enhanced sonography (CO2US) in
      assessing hepatocellular carcinoma (HCC) vascularities before and after
      treatment. Differences between PDUS and CEUS with the aid of CO2US were also
      observed. MATERIAL AND METHODS: In all, 43 patients with 67 histologically proved
      HCCs were examined with PDUS, CEUS, and CO2US. Among these tumors, 36 were HCCs
      before treatment and 31 were HCCs treated by transcatheter arterial
      chemoembolization or percutaneous ethanol injection or a combination of these two
      treatments. CO2US was used as the gold standard when comparing the PDUS and CEUS.
      RESULTS: Of the 36 untreated HCC tumors, 20 (55.6%) were hypervascular compared
      with the liver parenchyma at PDUS, 28 (77.8%) at CEUS, 31 (86.1%) at the early
      phase of CO2US and 32 (88.9%) at the late phase of CO2US. Of the 31 post
      treatment HCCs, 11 (35.5%) showed hypervascularity at PDUS, 25 (80.6%) at CEUS,
      25 (80.6%) at the early phase of CO2US and 26 (83.9%) at the late phase of CO2US.
      CONCLUSION: CO2US was superior to CEUS and CEUS was superior to PDUS for the
      detection of tumor vascularity in both untreated and treated HCCs. The duration
      of enhancement at CEUS was shorter than at CO2US. The ability of CO2US to detect
      additional small tumors was not possible with PDUS and CEUS.

PMID- 12225485
TI  - Non-Hodgkin's lymphoma in McKusick syndrome. A case report.
AB  - The McKusick syndrome in a female who developed highly malignant lymphoma at the
      age of 23, with multiple parenchymal lesions involving both kidneys, the lungs
      and the pancreas and also splenomegaly but without lymphadenopathy, is described
      together with diagnostic imaging findings. McKusick syndrome is associated with
      impaired cell-mediated immunity and might, like several other similar syndromes,
      harbor an increased risk of certain types of lymphoma. To our knowledge, there
      are no previous reports of non-Hodgkin's lymphoma in a patient with McKusick
      syndrome. The increased incidence of lymphoma in certain cases of congenital
      immunodeficiency raises the issue of a possible relationship between McKusick
      syndrome and lymphoma and could perhaps serve as one of the primary steps for a
      further characterization of this syndrome.

PMID- 12225486
TI  - Ganglion cysts of the cruciate ligaments.
AB  - PURPOSE: To evaluate the MR findings of ganglion cysts of the cruciate ligaments
      in correlation with clinical findings. MATERIAL AND METHODS: We reviewed 12
      patients with ganglion cysts of the cruciate ligaments obtained from a medical
      record of 4153 consecutive patients referred for knee MR examinations. All
      patients presented with chronic knee pain and 4 had restriction of knee motion.
      The MR imaging findings of the cysts were evaluated and correlated with clinical
      manifestations. RESULTS: Seven ganglion cysts were found in the posterior
      cruciate ligaments and 5 in the anterior cruciate ligaments. All cysts were
      lobulated (n=7) or fusiform (n=5) in shape, 1.8-4.5 cm in size, along the
      posterior surface in the proximal or distal end of the ligaments. Ten patients
      had arthroscopic resection or aspiration of their cysts, became symptom free and
      had no recurrence on follow-up MR examinations. Two cysts reduced in size
      spontaneously by conservative treatment. CONCLUSION: MR imaging can offer useful
      information in detection and diagnosis of patients with chronic knee pain due to
      ganglion cysts of the cruciate ligaments. The size and location of the ganglion
      cysts can attribute to the clinical manifestations.

PMID- 12225487
TI  - Fluoroscopy-guided intraarticular corticosteroid injection into the sacroiliac
      joints in patients with ankylosing spondylitis.
AB  - PURPOSE: Our goal was to prospectively study the therapeutic efficacy of CT
      marking and fluoroscopy-guided intraarticular corticosteroid instillation of
      inflamed sacroiliac joints in patients with ankylosing spondylitis. MATERIAL AND
      METHODS: A total of 22 fluoroscopy-guided intraarticular corticosteroid
      injections in the sacroiliac joints were performed in 17 patients with ankylosing
      spondylitis and severe low back pain. Needle puncture point, angle of
      intervention and distance of sacroiliac joint from the skin were determined by
      sacroiliac joint axial CT examination in prone position. 14 mg of betamethasone
      were instilled in each joint under fluoroscopy. RESULTS: Twenty of 22 joints
      (90.9%) reported good improvement during a month after corticosteroid injection
      of the sacroiliac joint. The remaining 2 joints reported fair improvement.
      CONCLUSION: CT-marking and fluoroscopy-guided intraarticular corticosteroid
      instillation in the sacroiliac joints may be regarded as an effective therapy.
      This technique was useful, rapid and safe.

PMID- 12225488
TI  - Primary muscular hydatidosis. US, CT and MR findings.
AB  - We present a rare case of primary muscular hydatidosis in the left thigh of a 40
      year-old female patient. US, CT and MR imaging showed a typical multilocular
      hydatid cyst deep in the vastus intermedius and vastus medialis muscles.
      Histopathological examination, which followed surgical excision, established the
      diagnosis of echinococcus cyst.

PMID- 12225489
TI  - Lymphoma of the cervix. Imaging and transcatheter arterial embolization.
AB  - A case of uterine cervix lymphoma with selective embolization after angiography
      is described. Chemotherapy and radiotherapy were carried out and surgery was
      avoided.

PMID- 12225490
TI  - Feasibility and assessment of non-invasive in vivo redox status using electron
      paramagnetic resonance imaging.
AB  - PURPOSE: To test the feasibility of electron paramagnetic resonance imaging
      (EPRI) to provide non-invasive images of tissue redox status using redox
      sensitive paramagnetic contrast agents. MATERIAL AND METHODS: Nitroxide free
      radicals were used as paramagnetic agents and a custom-built 300 MHz EPR
      spectrometer/imager was used for all studies. A phantom was constructed
      consisting of four tubes containing equal concentrations of a nitroxide. Varying
      concentrations of hypoxanthine/xanthine oxidase were added to each tube and
      reduction of the nitroxide was monitored by EPR as a function of time. Tumor
      bearing mice were intravenously infused with a nitroxide and the corresponding
      reduction rate was monitored on a pixel-by-pixel basis using 2D EPR of the tumor
      bearing leg and normal leg serving as control. For animal studies, nitroxides
      were injected intravenously (1.25 mmol/kg) and EPR projections were collected
      every 3 min after injection using a magnetic field gradient of 2.5 G/cm. The
      reduction rates of signal intensity on a pixel-by-pixel basis were calculated and
      plotted as a redox map. Redox maps were also collected from the mice treated with
      diethylmaleate (DEM), which depletes tissue thiols and alters the global redox
      status. RESULTS: Redox maps obtained from the phantoms were in agreement with the
      intensity change in each of the tubes where the signals were decreasing as a
      function of the enzymatic activity, validating the ability of EPRI to accurately
      access changes in nitroxide reduction. Redox imaging capability of EPR was next
      evaluated in vivo. EPR images of the nitroxide distribution and reduction rates
      in tumor-bearing leg of mice exhibited more heterogeneity than in the normal
      tissue. Reduction rates were found to be significantly decreased in tumors of
      mice treated with DEM, consistent with the depletion of thiols and the consequent
      alteration of the redox status. CONCLUSION: Using redox-sensitive paramagnetic
      contrast agents, EPRI can non-invasively discriminate redox status differences
      between normal tissue and tumors.

PMID- 12225491
TI  - Early psychosis reform: too fast or too slow?

PMID- 12225492
TI  - The Bech-Rafaelsen Melancholia Scale (MES) in clinical trials of therapies in
      depressive disorders: a 20-year review of its use as outcome measure.
AB  - OBJECTIVE: To evaluate the psychometric properties of the Bech-Rafaelsen
      Melancholia Scale (MES) by reviewing clinical trials in which it has been used as
      outcome measure. METHOD: The psychometric analysis included internal validity
      (total scores being a sufficient statistic), interobserver reliability, and
      external validity (responsiveness in short-term trials and relapse prevention in
      long-term trials). RESULTS: The results showed that the MES is a unidimensional
      scale, indicating that the total score is a sufficient statistic. The
      interobserver reliability of the MES has been found adequate both in unipolar and
      bipolar depression. External validity including both relapse, response and
      recurrence indicated that the MES has a high responsiveness and sensitivity.
      CONCLUSION: The MES has been found a valid and reliable scale for the measurement
      of changes in depressive states during short-term as well as long-term treatment.

PMID- 12225493
TI  - Duration of untreated psychosis and its correlates in first-episode psychosis in
      Finland and Spain.
AB  - OBJECTIVE: To examine the association of duration of untreated psychosis (DUP)
      with early course characteristics in first-episode psychosis in Finland and
      Spain. METHOD: Eighty-six patients from Finland (49) and Spain (37) were
      evaluated on various early course characteristics. RESULTS: The mean value of DUP
      was 4.0 months (median 2 months) for the Finnish patients and 9.9 months (median
      2 months) for the Spanish ones. In both groups, long DUP was associated with
      insidious onset, poor global functioning, and laboral incapability. Among the
      Finnish patients exclusively, long DUP correlated with a weak earlier social
      network, instability of professional identity, long duration of prodromal
      symptoms, psychological dependency on the family, and criticism by the parents of
      the patient. Among the Spanish patients only, longer DUP was associated with more
      severe positive symptoms at admission. CONCLUSION: There are universal
      psychosocial factors influencing DUP, but also cultural differences may have an
      impact on the treatment delay.

PMID- 12225494
TI  - One-year outcome in first episode psychosis patients in the Swedish Parachute
      project.
AB  - OBJECTIVE: Implementing a system designed to treat first episode psychotic (FEP)
      patients. METHOD: Every FEP patient (n=253) from a catchment area of 1.5 million
      inhabitants were asked to participate in this 5-year project. One historical
      (n=71) and one prospective (n=64) FEP group were used for comparisons. RESULTS: A
      total of 175 patients (69%) were followed up through the first year of treatment.
      Global Assessment of Functioning (GAF) values were significantly higher than in
      the historical comparison group but similar to the prospective group. Psychiatric
      in-patient care was lower as was prescription of neuroleptic medication.
      Satisfaction with care was generally high in the Parachute group. Access to a
      small overnight crisis home was associated with higher GAF. CONCLUSION: It is
      possible to successfully treat FEP patients with fewer in-patient days and less
      neuroleptic medication than is usually recommended, when combined with intensive
      psychosocial treatment and support.

PMID- 12225495
TI  - Medication adherence of individuals with a first episode of psychosis.
AB  - OBJECTIVE: To determine rates of adherence to antipsychotic medication in first
      episode patients and the correlates of adherence in this group. METHOD: Subjects
      were the first 200 admissions to an Early Psychosis Program. Adherence was
      determined on a three-point scale. Symptoms, medication side-effects, quality of
      life, substance use and family involvement were examined longitudinally. RESULTS:
      In their first year in the program 39% were non-adherent, 20% inadequately
      adherent, and 41% adherent. Non-adherent patients demonstrated more positive
      symptoms, more relapses, more alcohol and cannabis use, reduced insight, and
      poorer quality of life. They were younger, had an earlier age of onset and less
      likely to have a family member involved in treatment. CONCLUSION: Results for
      this group are similar to those reported in the literature. Correlates are often
      the consequence of non-adherence. Non-compliance has to be anticipated and
      relationships maintained with patients and families to intervene as soon as
      possible to minimize the consequence of non-compliance.

PMID- 12225496
TI  - The impact of professional and social network support on the burden of families
      of patients with schizophrenia in Italy.
AB  - OBJECTIVE: (a) To explore burden related to caregiving and support received from
      professionals and social network in relatives of patients with schizophrenia in
      Northern, Central and Southern Italy; and (b) to test whether a higher level of
      family burden is associated with a lower level of professional and social network
      support. METHOD: Seven hundred and nine patients with schizophrenia and their key
      relatives were consecutively recruited in 30 Italian mental health departments.
      Data were collected on: (a) patients' clinical status and levels of disability;
      (b) relatives' burden, social and professional support; (c) interventions
      received by patients and their families. RESULTS: Family burden was found lower
      in Northern Italy. However, after controlling for psychosocial interventions,
      differences in family burden among the three geographical areas disappeared.
      Family burden was associated with patients' levels of disability and
      manic/hostility symptoms, and with professional and social network support
      received by the family. CONCLUSION: Professional and social network support
      represent crucial resources to reduce family burden in schizophrenia.

PMID- 12225497
TI  - Seasonal distribution of suicide in alcoholism.
AB  - OBJECTIVE: To investigate the seasonal distribution of suicide in alcohol
      dependence and to make a comparison with unnatural death in alcoholism and
      suicide in other diagnostic groups. METHOD: Multiaxial ratings of all patients
      admitted to the Department of Psychiatry in Lund enabled the selection of
      patients with alcohol dependence (n=1312) during 1949-1969. When followed up to
      1997 a total of 102 (99 men) alcoholic patients had taken their own life.
      Reference groups were patients with severe depression and autopsy cases with
      other diagnoses. RESULTS: The alcoholic patients showed a peak during the second
      quarter of the year (34%, P < 0.05). Other diagnostic groups of suicide and
      unnatural death in alcoholism did not show any overrepresentation in the spring.
      CONCLUSION: Male alcoholics showed a spring peak of suicide as opposed to other
      diagnostic groups.

PMID- 12225498
TI  - Predictors of first incidence of DSM-III-R psychiatric disorders in the general
      population: findings from the Netherlands Mental Health Survey and Incidence
      Study.
AB  - OBJECTIVE: To investigate determinants of 12-month first incidence of DSM-III-R
      mood disorder (MD), anxiety disorder (AD) and substance use disorder (SUD) in the
      general population. METHOD: Data are from the Netherlands Mental Health Survey
      and Incidence Study (NEMESIS), a prospective epidemiologic study in which a
      representative sample of 7076 adults aged 18-64 years were interviewed with the
      Composite International Diagnostic Interview. New cases diagnosed 12 months after
      baseline were compared with never diagnosed controls on sociodemographic and
      psychosocial variables. RESULTS: Multivariate, the only demographic variable
      associated with incidence of MD was female gender. The strongest predictors were
      negative life events and ongoing difficulties. High level of neuroticism was also
      associated. Incidence of AD was likewise predicted by female gender. Negative
      life events and ongoing difficulties were also significant predictors, though
      weaker than for MD. Incidence of SUD was more common among males, young adults,
      people not living with a partner and those experiencing positive life events.
      CONCLUSION: Incident MD and AD were predicted more strongly by life events, and
      SUD more strongly by demographic factors.

PMID- 12225499
TI  - Addition of cognitive-behaviour therapy for obsessive-compulsive disorder
      patients non-responding to fluoxetine.
AB  - OBJECTIVE: Selective serotonin re-uptake inhibitors (SSRIs) and cognitive
      behaviour therapy (CBT) have both proven to be effective in the treatment of
      obsessive compulsive disorder (OCD). It is generally recommended that adequate
      but unsuccessful SSRI treatment is supplemented with CBT, although only one
      empirical study was conducted to verify this recommendation. The present study
      examined the effects of supplemental CBT to continued fluoxetine treatment in OCD
      patients non-responding to fluoxetine alone. METHOD: After 12 weeks of
      fluoxetine, 14 of 56 out-patients had a reduction rate less than 25% on the Yale
      Brown Obsessive Compulsive Scale (Y-BOCS) and were classified as non-responders.
      They subsequently received 12 sessions CBT additional to the continued fluoxetine
      treatment. RESULTS: The mean symptom reduction as rated by the Y-BOCS, for the
      patients who completed both treatment phases, was 8.5% in the first phase and 41%
      in the second phase. CONCLUSION: Supplemental CBT for OCD patients, after
      initial, unsuccessful fluoxetine treatment is shown to be effective.

PMID- 12225500
TI  - Editorial: The cardiovascular disease epidemic: global, regional, local.

PMID- 12225501
TI  - Clinical predictors of bacterial meningitis in infants and young children in The
      Gambia.
AB  - BACKGROUND: Bacterial meningitis is an important cause of childhood morbidity and
      mortality world-wide. In the developing world, where the burden of acute
      meningitis and its long-term sequelae are especially high, staff with limited
      training at primary health care facilities must be able to recognize the symptoms
      and signs of meningitis, so that suspected cases can be referred urgently to
      hospitals. METHODS: Children who presented with possible invasive bacterial
      infection to health facilities in The Gambia, West Africa, between 1993 and 1995
      were investigated in a standardized manner and clinical findings were documented.
      Bacterial meningitis was defined as the growth of bacteria from the cerebrospinal
      fluid. Clinical findings were compared between cases of meningitis and other
      children. RESULTS: Of 2097 children between 2 months and 3 years of age
      investigated, 51 had a confirmed diagnosis of bacterial meningitis. In
      multivariate analysis using a model adjusting for age but not including
      respiratory signs, the variables associated independently with meningitis were
      appearance of being very sick (odds ratio for meningitis vs. no meningitis or no
      lumbar puncture performed (OR) 4.1, 95% CI 1.5-11.1), being lethargic or
      unconscious (OR 5.2, 95% CI 2.1-13), a stiff neck (OR 29.3, 95% CI 12.2-70.3), a
      bulging fontanel (OR 3.2, 95% CI 1.2-8.5) and reduced feeding as a prompted
      complaint (OR 2.9, 95% CI 1.3-6.7). A combination model of a history of
      convulsions, or being lethargic or unconscious, or having a stiff neck, as used
      in the WHO-Integrated Management of Childhood Illness (IMCI) guidelines, had a
      sensitivity of 98% and a specificity of 72% to predict meningitis. CONCLUSIONS: A
      combination of a limited number of signs is sufficient to predict meningitis with
      high sensitivity, without a large number of children who do not have meningitis
      being unnecessarily referred.

PMID- 12225502
TI  - Malaria control by residual insecticide spraying in Chingola and Chililabombwe,
      Copperbelt Province, Zambia.
AB  - Malaria is endemic in the whole of Zambia and is the leading cause of morbidity
      and mortality. Prior to 1980, effective malaria control was achieved in the
      northern mining towns of Chingola and Chililabombwe by means of annual residual
      spraying programmes. In the 1970s, incidence rates were as low as 20/1000 p.a.,
      but by 2000 had increased to 68/1000 p.a. in Chingola and to 158/1000 p.a.in
      Chililabombwe. Konkola Copper Mines (KCM) initiated a malaria control programme
      in which all dwellings in the two towns and within a 10-km radius were sprayed
      with either dichlorodiphenyltrichloroethane or a synthetic pyrethroid (Icon by
      ZENECA or Deltamethrin by Aventis). Houses were sprayed in November and December
      2000, at the start of the peak transmission period. There was a statistically
      significant reduction in malaria incidence recorded at KCM health facilities in
      the two towns, representing a protective incidence rate ratio of 0.65 (95% CI
      0.44, 0.97) when comparing the post-spraying period with the corresponding period
      of the previous 2 years. This reduction followed a single round of house spraying
      during a year with higher rainfall than the preceding two and in an area where
      chloroquine was first-line treatment. This house-spraying programme is an example
      of private/public sector collaboration in malaria control.

PMID- 12225503
TI  - In vivo drug resistance of falciparum malaria in mining areas of Venezuela.
AB  - The Lot Quality Assurance Double-Sampling Plan (LQADSP) technique was used in
      three areas, Maripa, Kilometro 88 and Ikabaru, to assess the efficacy of
      antimalarials used routinely by the Venezuelan Malaria Programme. The use of
      chloroquine (25 mg/kg), chloroquine (40 mg/kg) and the combination of sulfadoxine
      (500 mg) and pyrimethamine (25 mg) registered treatment failures above the
      threshold level of 25% in Maripa and Kilomertro 88. In Ikabaru the use of
      chloroquine (40 mg/kg) did not surpass that quality level and could possibly be
      less than 10%. Quinine (30 mg/kg) was totally effective in curing patients in all
      three areas. The use of this technique seems adequate for rapid field evaluations
      and in this case for providing appropriate information to assist this health
      programme. However, whilst being an ideal technique for surveying areas in which
      considerable variation may exist among lots and particularly for Plasmodium
      falciparum infections in these areas, repeated surveys should be carried out in
      the same areas over time to monitor changes in the susceptibility of this
      parasite to first-, second- and third-line drugs. In that way, national drug
      policies can be modified adequately.

PMID- 12225504
TI  - Barriers to prompt and effective treatment of malaria in northern Sri Lanka.
AB  - BACKGROUND: For the past 18 years, northern Sri Lanka has been affected by armed
      ethnic conflict. This has had a heavy impact on displacement of civilians, health
      delivery services, number of health professionals in the area and infrastructure.
      The north of Sri Lanka has a severe malaria burden, with less than 5% of the
      national population suffering 34% of reported cases. Health care providers
      investigated treatment-seeking behaviour and levels of treatment failure believed
      to be the result of lack of adherence to treatment. METHODS: Pre- and post
      treatment interviews with patients seeking treatment in the outpatient department
      (OPD) and focus groups. RESULTS: A total of 271 persons completed interviews:
      54.4% sought treatment within 2 days of the onset of symptoms, and 91.9% self
      treated with drugs with prior to seeking treatment, mainly with paracetamol. Self
      treatment was associated with delaying treatment (RR 3.55, CI 1.23-10.24,
      P=0.002). In post-treatment interviews, self-reported default was 26.1%. The main
      reasons for not taking the entire regimen were side-effects (57.6%) and
      disappearance of symptoms (16.7%). Focus groups indicated some lack of confidence
      in chloroquine treatment and prophylaxis, and scant enthusiasm for prevention
      methods. CONCLUSIONS: A number of factors contribute to a lack of access and a
      lower quality of care for malaria: lack of medical staff and facilities because
      of the fighting; lack of confidence in treatment, and perception of malaria as a
      routine illness. Prevention efforts need to take into account certain beliefs and
      practices to be successful.

PMID- 12225505
TI  - Diarrhoea and effects of different water sources, sanitation and hygiene
      behaviour in East Africa.
AB  - Apart from "Drawers of Water (DOW I)" published in 1972, there have been only a
      handful of published studies on domestic water use and environmental health in
      East Africa, based on direct observations or other reliable research methods. The
      objective of this study was to carry out a repeat analysis of domestic water use
      and environmental health in East Africa based on DOW I. The study was conducted
      in the same sites as DOW I. Field assistants spent at least 1 day in each
      household observing and conducting semi-structured interviews. They measured the
      amount of water collected, recorded the amount of water used in the home, and
      noted household socio-demographic characteristics, prevalence of diarrhoea, state
      and use of latrines, sources of water and conditions of use. We surveyed 1015
      households in 33 sites in Uganda, Tanzania and Kenya in 1997. From 1967 to 1997,
      the prevalence of diarrhoea, in the week preceding the survey, increased from 6%
      to 18% in Kenya and from 16% to 21% in Uganda; it declined slightly in Tanzania
      (11-8%). Determinants of diarrhoea morbidity included poor hygiene (unsafe
      disposal of faeces and wastewater), education level of household head, obtaining
      water from surface sources or wells and per capita water used for cleaning.
      Hygiene practices are an important complement to improved water and sanitation in
      reducing diarrhoea morbidity.

PMID- 12225506
TI  - Dynamics of dengue virus circulation: a silent epidemic in a complex urban area.
AB  - Serotypes of dengue DEN-1 and DEN-2 have been reported in much of Brazil over the
      last 15 years, and DEN-3 serotype was only recently detected. This prospective
      study was conducted in Salvador, a large city in north-east Brazil, where two
      epidemics were previously recorded (DEN-1 and DEN-2). We obtained the
      seroprevalence and 1-year incidence of dengue infections in the population of 30
      sampling areas of Salvador and analysed the relationship between intensity of
      viral circulation, standard of living and vector density. High seroprevalence
      (68.7%) and annual incidence (70.6%) of infection for one or both circulating
      serotypes (DEN-1 and DEN-2) were found. High rates of transmission were observed
      in all studied areas, from the highest to the lowest socio-economic status. The
      mean PI (Premise Index) for Aedes aegypti was 7.4% (range 0.27-25.6%). Even in
      the areas with the lowest PI (</=3%) the observed seroincidence was 54.6%. These
      findings highlighted the existence of a silent epidemic during a period perceived
      by the Health Services as of low endemicity, indicating the strength and speed of
      dengue transmission in the city of Salvador.

PMID- 12225507
TI  - Efficacy and sustainability of a footcare programme in preventing acute attacks
      of adenolymphangitis in Brugian filariasis.
AB  - Lymphatic filariasis is associated with considerable disability related to the
      intensity and frequency of acute adenolymphangitis (ADL) attacks. The global
      programme for elimination of lymphatic filariasis emphasizes the need to combine
      transmission control with alleviation of disability. Footcare aimed at the
      prevention of secondary bacterial infections is the mainstay of disability
      alleviation programmes. We evaluated the efficacy and sustainability of an
      unsupervised, personal footcare programme by examining and interviewing 127
      patients who had previously participated in a trial that assessed the efficacy of
      diethylcarbamazine, penicillin and footcare in the prevention of ADL. During the
      trial period these patients had been educated in footcare and were supervised.
      During the unsupervised period, which lasted 1 year or longer, 47 patients
      developed no ADL, and ADL occurred less frequently in 72.5%. Most patients were
      practising footcare as originally advised, unsupervised and without cost, which
      proves that such a programme is sustainable and effective.

PMID- 12225508
TI  - The effect of six rounds of single dose mass treatment with diethylcarbamazine or
      ivermectin on Wuchereria bancrofti infection and its implications for lymphatic
      filariasis elimination.
AB  - Annual mass treatment with single-dose diethylcarbamazine (DEC) or ivermectin
      (IVM) in combination with albendazole (ALB) for 4-6 years is the principal tool
      of lymphatic filariasis (LF) elimination strategy. This placebo-controlled study
      examined the potential of six rounds of mass treatment with DEC or IVM to
      eliminate Wuchereria bancrofti infection in humans in rural areas in south India.
      A percentage of 54-75 of the eligible population (> or =15 kg body weight)
      received treatment during different rounds of treatment - 27.4% in the DEC arm
      and 30.7% in the IVM arm received all six treatments, 4.8% and 5.6% received
      none, and the remainder received one to five treatments. After six cycles of
      treatment, the microfilaria (Mf) prevalence in treated communities dropped by 86%
      in the DEC arm (P < 0.01) (n = 5 villages) and by 72% in the IVM arm (P < 0.01)
      (n = 5 villages), compared with 37% in the placebo arm (P < 0.05) (n = 5
      villages). The geometric mean intensity of Mf fell by 91% (t = 8.11, P < 0.05),
      84% (t = 6.91, P < 0.05) and 46% (t = 2.98, P < 0.05) in the DEC, IVM and placebo
      arms, respectively. The proportion of high-count Mf (>50 Mf per 60 mm(3) of
      blood) carriers was reduced by 94% (P < 0.01) in the DEC arm and by 90% (P <
      0.01) in the IVM arm. Among those who received all six treatments, 1.4% in the
      DEC arm and 2.4% in the IVM arm remained positive for Mf. Two of five villages in
      the DEC arm and one of five in the IVM arm showed zero Mf prevalence, but
      continued to have low levels of transmission of infection. The results also
      indicate that DEC is as effective as or slightly better than IVM against
      microfilaraemia. Results from this and other recent operational studies proved
      that single-dose treatment with antifilarials is very effective at community
      level, feasible, logistically easier and cheap and hence a highly appropriate
      strategy to control or eliminate LF. Higher treatment coverage than that observed
      in this study and a few more than six cycles of treatment and more effective
      treatment tools/strategies may be necessary to reduce microfilaraemia to zero
      level in all communities, which may lead to elimination of LF.

PMID- 12225509
TI  - Combination of eflornithine and melarsoprol for melarsoprol-resistant Gambian
      trypanosomiasis.
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of a combination of eflornithine
      and melarsoprol among relapsing cases of Gambian trypanosomiasis. METHODS: Forty
      two late-stage Trypanosoma brucei gambiense trypanosomiasis patients relapsing
      after initial treatment with melarsoprol were treated with a sequential
      combination of intravenous eflornithine (100 mg/kg every 6 h for 4 days) followed
      by three daily injections of melarsoprol (3.6 mg/kg, up to 180 mg). They were
      then followed-up for 24 months. RESULTS: Two (4.8%) patients died during
      treatment. Of the 40 surviving patients, two had a treatment failure, 13 and 19
      months after having received the combination therapy. By Kaplan-Meier analysis,
      the 2-year probability of cure was 93.3% (95% confidence interval: 84.3-100%).
      CONCLUSION: This sequential combination has an efficacy and a toxicity similar to
      a 7-day course of eflornithine monotherapy, but is easier to administer. Whether
      such therapeutic success corresponds tosynergism between eflornithine and
      melarsoprol, or merely means that 4 days of eflornithine monotherapy suffices for
      such patients, will need to be determined in a comparative trial.

PMID- 12225510
TI  - Epidemiology of leprosy on five isolated islands in the Flores Sea, Indonesia.
AB  - We conducted a population-based survey on five small islands in South Sulawesi
      Province (Indonesia) to collect baseline data previous to a chemoprophylactic
      intervention study aiming at interrupting the transmission of Mycobacterium
      leprae. Here we describe the present leprosy epidemiology on these geographically
      isolated islands. Of the 4774 inhabitants living in the study area 4140 were
      screened for leprosy (coverage: 87%). We identified 96 leprosy patients (85 new
      and 11 old patients), representing a new case detection rate (CDR) of 205/10 000
      and a prevalence rate of 195/10 000. CDRs were similar for males and females.
      Male patients were more often classified as multibacillary (MB) than women. Of
      the new patients, 33 (39%) were classified as MB, 16 (19%) as paucibacillary (PB)
      2-5 lesions and 36 (42%) as PB single lesion. In this area of high leprosy
      endemicity leprosy patients were extensively clustered, i.e. not equally
      distributed among the islands and within the islands among the houses.

PMID- 12225511
TI  - Epidemiological aspects of mycetoma from a retrospective study of 264 cases in
      West Bengal.
AB  - Between 1981 and 2000, 264 cases of mycetoma were diagnosed clinically and
      microbiologically at Calcutta School of Tropical Medicine. Retrospective analysis
      of the records revealed that the ratio of actinomycetomas and eumycetomas was 197
      : 67; the male to female ratio was 183 : 81. Ninety-four cases occurred in the
      1980s and 170 in 1990s, with significantly more infections of Actinomadura spp.
      (P < 0.01) and fewer with Nocardia caviae (P < 0.01) during the last decade.
      Pricking was the most common injury associated with eumycetomas (P < 0.01). A
      total of 196 infections were in exposed body parts and 68 in covered areas. The
      localization of mycetomas differed significantly (P < 0.01) according to sex,
      incidence of actinomycetomas or eumycetomas, and obvious history of trauma.
      Exposed area cases were more common among agricultural workers (P < 0.01), while
      covered area mycetomas were almost always actinomycetomas with a remarkably lower
      incidence of N. caviae, A. madurae and Madurella grisea infections. The peak age
      of onset was between 16 and 25 years. The delay of diagnosis for the 80th
      percentile of cases was around 6 years for cases caused by N. brasiliensis and
      Streptomyces spp.; 8 years for N. caviae and N. asteroides; and 10 years for M.
      grisea and Actinomadura spp. From the history of trauma in 130 patients, the 80th
      percentile incubation period (IP) was calculated for N. brasiliensis, N. caviae
      and N. asteroides as 3 years; for Actinomadura spp. 7 years and for M. grisea 9
      years. The minimum IP for all organisms was around 3 months.

PMID- 12225512
TI  - Socioeconomic status and risk of HIV infection in an urban population in Kenya.
AB  - OBJECTIVE: To examine the relationship between socioeconomic status (SES), risk
      factors for HIV infection and HIV status in an urban population with high
      prevalence of HIV infection in sub-Saharan Africa. METHODS: Cross-sectional
      population survey of adults from the city of Kisumu, Kenya, in 1996. Around 1000
      men and 1000 women aged 15-49 years were interviewed using a structured
      questionnaire, and most gave a venous blood sample for HIV testing. SES was
      represented by a composite variable of educational status, occupation and
      household utilities. Multiple regression was used to examine whether SES was
      associated with HIV infection or with risk factors for HIV infection. RESULTS:
      Human immunodeficiency virus prevalence was 19.8% in males and 30.2% in females.
      Higher SES was associated with a more mobile lifestyle, later sexual debut and
      marriage among both sexes, and with circumcision among men aged 25-49 and condom
      use among women aged 25-49. Higher levels of alcohol consumption were associated
      with an increased risk of HIV infection and were more common amongst those of
      higher SES. HSV-2 infection was strongly associated with an increased risk of HIV
      infection and was more common among those of lower SES. HIV was associated with a
      lower SES among females aged 15-24 whereas in males aged 15-24 and females aged
      25-49 there was some indication that it was associated with higher SES. Among
      males aged 25-49 there was no association between HIV infection and SES.
      CONCLUSIONS: Risk of infection was high among groups of all SES. Risk profiles
      suggested men and women of lower SES maybe at greater risk of newly acquired HIV
      infection. New infections may now be occurring fastest among young women of the
      lowest SES.

PMID- 12225513
TI  - Private pharmacies in Hanoi, Vietnam: a randomized trial of a 2-year multi
      component intervention on knowledge and stated practice regarding ARI, STD and
      antibiotic/steroid requests.
AB  - OBJECTIVES: To assess the effectiveness of a multi-component intervention on
      knowledge and reported practice amongst staff working in private pharmacies in
      Hanoi regarding four conditions: urethral discharge [sexually transmitted
      diseases (STD)], acute respiratory infection (ARI), and non-prescription requests
      for antibiotics and steroids. METHOD: Randomized controlled trial with staff
      working in 22 matched pair intervention and control private pharmacies who were
      administered a semistructured questionnaire on the four conditions before and 4
      months after the interventions. The interventions focused on the four conditions
      and were in sequence (i) regulations enforcement; (ii) face-to-face education and
      (iii) peer influence. Outcome measures were knowledge and reported change in
      practice for correct management of tracer conditions. RESULTS: The
      intervention/control-pairs (22 after drop-outs) were analysed pre- and post
      intervention using the Wilcoxon signed rank test. STD: More drug sellers stated
      they would ask about the health of the partner (P = 0.03) and more said they
      would advise condom use (P = 0.01) and partner notification (P = 0.04). ARI: More
      drug sellers stated they would ask questions regarding fever (P = 0.01), fewer
      would give antibiotics (P = 0.02) and more would give traditional medicines (P =
      0.03). Antibiotics request: Fewer said they would sell a few capsules of
      cefalexin without a prescription (P = 0.02). Steroid requests: No statistical
      difference was seen in the numbers who said they would sell steroids without a
      prescription as numbers declined in both intervention and control groups (P =
      0.12). CONCLUSION: The three interventions in series over 17 months were
      effective in changing the knowledge and reported practice of drug sellers in
      Hanoi.

PMID- 12225514
TI  - Abstracts of the XX Annual Scientific Meeting of the British Blood Transfusion
      Society. Edinburgh, United Kingdom, 4-8 September 2002.

PMID- 12225544
TI  - Current respiratory syncytial virus prevention strategies in high-risk infants.
AB  - Respiratory syncytial virus (RSV) was initially isolated in 1956. Since then it
      has become recognized as a major pathogen worldwide. It is a ubiquitous pathogen
      that produces seasonal epidemics. Primary infection occurs in children before 2
      years of age. In older children and adults, RSV usually manifests itself as an
      upper respiratory tract infection. In immunecompromised patients, those with
      underlying cardiopulmonary disorders, premature infants, and other vulnerable
      individuals, RSV infection can produce severe bronchiolitis or pneumonia. In
      recent years we have observed exciting new information about the prevention of
      serious RSV infection in high-risk infants including infection control practices,
      active immunity and passive immunity. Two immunoprophylaxis products (RSV i.v.
      immune globulin and palivzumab) have been developed for clinical use in the
      prevention of serious RSV infection. Many other agents including vaccines, super
      monoclonal antibodies, and antivirals are under development. Although clinicians
      now have the ability to provide their most vulnerable patients with meaningful
      prevention strategies, much more needs to be done before we can regard RSV as a
      preventable disease.

PMID- 12225546
TI  - Follow-up study of auditory brainstem responses in infants with high unbound
      bilirubin levels treated with albumin infusion therapy.
AB  - BACKGROUND: Several authors reported that there was a close relationship between
      unbound bilirubin concentrations and abnormal results of auditory brainstem
      responses. Full-term infants with high-unbound bilirubin concentrations who were
      treated with human albumin were followed to evaluate their hearing abilities by
      using auditory brainstem responses. METHODS: Fifty-eight infants (gestational
      age, 39.4 +/- 1.4 weeks; birthweight, 3,245 +/- 435 g) with high unbound
      bilirubin concentrations (> or = 0.9 micro g/dL) were treated with intensive
      phototherapy. Twenty infants (control group) received only phototherapy, while 38
      others (albumin-treated group) were also given i.v. human albumin administration
      (1 g/kg bodyweight) during the first 2 h of phototherapy. The follow-up study of
      auditory brainstem responses was carried out at 6 and 12 months of age.
      Development quotient tests were carried out at 18 months of age. RESULTS:
      Abnormalities of auditory brainstem response were detected in three infants in
      the albumin-treated group and six infants in the control group at 6 months. Two
      infants in the albumin-treated group and four infants in the control group had
      improved at 12 months. The results of the follow-up study at 18 months of age in
      the both groups were normal with development quotient >85. No patients with
      hearing disability and cerebral palsy were clinically detected at the age of 2
      years. CONCLUSION: The results suggest that albumin priming might be effective
      for decreasing the rate of auditory brainstem response abnormalities at 6 months.

PMID- 12225545
TI  - Response of anti-oxidant enzymes mRNA in the neonatal rat liver exposed to
      1,2,3,4-tetrachlorodibenzo-p-dioxin via lactation.
AB  - BACKGROUND: The aim of this study was to assess the response to dioxin-induced
      oxidative stress in neonates via lactation in the model we have described
      previously. METHODS: Maternal rats were treated with a single dose of 50 or 100
      micro mol/kg 1,2,3,4-tetrachlorodibenzo-p-dioxin (TCDD) on the first day
      postpartum (day 1). Messenger RNA levels of the key anti-oxidant enzymes (AOE),
      phospholipid hydroperoxide-glutathione peroxidase (PH-GPx), cellular-glutathione
      peroxidase (cell-GPx), copper-zinc superoxide dismutase (CuZn SOD), manganese
      superoxide dismutase (Mn SOD) and catalase (CAT) in the neonatal and maternal
      livers were determined by a competitive reverse transcription- polymerase chain
      reaction method. RESULTS: Lactational transfer of 1,2,3,4-TCDD induced an
      inhibition of PH-GPx and cell-GPx mRNA in the neonatal liver on day 2 to 68 (P <
      0.01) and 62% (P < 0.05) of the control at 100 micro mol/kg, respectively. Both
      GPx mRNA returned to control levels on day 6 and thereafter increased to levels
      higher than the controls on day 10. In the dam rat, 10 days after the treatment,
      no remarkable change of PH-GPx or cell-GPx mRNA was observed. Copper-zinc
      superoxide dismutase and CAT mRNA of neonates on day 2 were also suppressed at
      100 micro mol/kg and then slightly increased on day 10. However, Mn SOD mRNA was
      not suppressed, but increased to a 2.1-fold level of the control (P < 0.05) on
      day 10 with 100 micro mol/kg 1,2,3,4-TCDD. CONCLUSION: Quantitative analysis of
      AOE mRNA showed that PH-GPx and cell-GPx mRNA, as well as CuZn SOD and CAT mRNA
      in the neonatal liver were suppressed for a short period of time by 1,2,3,4-TCDD
      exposure via lactation. Dioxin induced oxidative stress by lactational transfer
      may alter pretranslation regulation of protective AOE in neonates.

PMID- 12225547
TI  - Development of chronic lung disease in preterm infants treated with surfactant.
AB  - BACKGROUND: Chronic lung disease (CLD) is generally known to develop among
      preterm infants who have severe respiratory distress syndrome (RDS) at birth.
      Many clinical trials have established the efficacy of surfactant replacement
      therapy to treat RDS at birth with differing doses. In this study, the preterm
      infants diagnosed to have RDS at birth and treated with one or two doses of
      surfactant, depending on the severity of the RDS, were studied to evaluate the
      effect of surfactant on the later development of CLD. METHODS: A retrospective
      examination of case records of preterm infants who were born at < or = 28 weeks
      gestation period were studied. The subjects received a natural surfactant product
      (survanta) between September 1994 and April 1996 at the Monash Medical Center,
      Australia. RESULTS: Despite less severe initial lung disease, the subsequent
      respiratory outcome of infants who received one dose of surfactant, showed a
      trend towards being poorer compared to those who were diagnosed as having severe
      RDS at birth and received two doses of surfactant. At the corrected gestational
      age of 36 weeks, 54% of those infants began with mild RDS required oxygen, while
      only 44% of those who started with a severe RDS required supplemental O2.
      CONCLUSION: This study reports the infants with severe RDS at birth had responded
      slightly better or equally, compared to those with mild RDS, in terms of later
      development of CLD under surfactant treatment proportional to the severity.

PMID- 12225548
TI  - Different expression of surfactant protein B mature peptide and proprotein at 21
      weeks' gestation in human fetal pulmonary epithelial cells.
AB  - AIM: The aim of this study is to evaluate the maturation of pulmonary epithelial
      cells in human fetal lungs at 21 weeks' gestation. METHODS: Eight fetuses at 21
      weeks' gestation were evaluated. The maturation of pulmonary epithelial cells was
      assessed by immunohistochemical examination for surfactant proteins and by
      electron microscopy. RESULTS: Surfactant protein B mature peptide was detected
      slightly in the epithelial lining of the bronchioles, but was totally absent in
      the terminal airways. Surfactant protein B proprotein was clearly detected in the
      epithelial lining of both bronchioles and terminal airways. Transmission electron
      microscopy of terminal airway cells showed abundant glycogen granules and few
      intracellular organelles. CONCLUSIONS: The production of mature surfactant
      protein B in terminal airways is scarce at 21 weeks' gestation, which is
      associated with the immature mechanism of proprotein processing in the cytoplasm.

PMID- 12225550
TI  - Prevalence of Mycoplasma pneumoniae in children in Diyarbakir, the south-east of
      Turkey.
AB  - BACKGROUND: Mycoplasma pneumoniae is a well known causative agent of infection in
      childhood but clinical presentation may be variable. History and physical
      examination may not be so helpful for the diagnosis. It is difficult to culture
      this infectious agent, with the culture technique for the multiplication of the
      organism for routine investigation hard to obtain. The determination of exposure
      and prevalence of the disease of any region should be helpful for clinical
      diagnosis. In this study, we aimed to determine the seroprevalence of M.
      pneumoniae in children aged 0-14 years in Diyarbakir and establish the
      distribution of infection prevalence of various age groups of children. METHODS:
      Thirty streets were determined according to the cluster method for the 0-6 years
      age group. In this age group, a total of 180 blood samples were collected; so
      that there were 30 samples for each age. For children aged 7-14 years, elementary
      school children were selected. There were 70 elementary schools in the city and
      14 schools were randomly selected according to the randomized numbers table with
      a 20% sample. Finally, 276 blood samples were collected. Mycoplasma pneumoniae
      was determined by using the enzyme immunoassay method. For this method MELOTEST
      Mycoplasma IgG reagent was used. RESULTS: The highest seropositivity rate was
      encountered at 10 years of age (65%) and lowest was at 2 years of age (0%). The
      overall M. pneumoniae seropositivity was 27% when all ages were considered
      together. The first 2 years of age excluded this rate and was 31.9%. A sudden
      increase of seropositivity was observed at 7 years of age. CONCLUSIONS:
      Increasing seroprevalence rates of M. pneumoniae after 2 years of age should
      alert clinicians to consider the organism in the differential diagnosis of
      infectious diseases in this age group. The low seroprevalence rates in the first
      2 years of age was thought to be due to low risk of community-based spread of the
      organism in this age group. The most prominent increase in seroprevalence was at
      10 years of age. This data indicated that M. pneumoniae should be kept in mind
      while making differential diagnosis of infections. The spreading of disease and
      community-based transmission is also important to consider. In our study,
      seroprevalence rates increased at 6 and 7 years of age, at the beginning of the
      school age as community-based transmission takes place most commonly in crowded
      circumstances. In conclusion, M. pneumoniae should be thought as an important
      infectious agent in childhood for all age groups.

PMID- 12225549
TI  - Randomized controlled trial of magnesium sulfate infusion for severe birth
      asphyxia.
AB  - OBJECTIVE: To determine whether postnatal MgSO(4) infusion (250 mg/kg per day)
      for 3 days is both safe and able to improve outcome in infants with severe birth
      asphyxia, as had been suggested by a small pilot study. METHODS: A multicenter
      randomized controlled trial was conducted. Entry criteria included 5-min Apgar
      score of seven or less and either failure to initiate spontaneous respiration at
      10 min after birth because of asphyxia, or occurrence of clinically apparent
      seizures within 24 h after birth. Number of subjects was calculated to detect a
      50% reduction in incidence of adverse outcomes. RESULTS: Distributions of
      perinatal factors, neonatal baseline characteristics and severity of hypoxic
      ischemic encephalopathy were similar in treated and control groups. No
      significant differences were observed in duration of clinical seizures, or need
      for assisted ventilation. Survival with normal results of cranial computed
      tomography, electroencephalography and establishment of oral feeding by 14 days
      of age, was significantly more frequent in the treated group than in the control
      group (12/17 vs 5/16, P = 0.04). No significant differences in blood pressure,
      heart rate or respiratory rate were observed between groups. CONCLUSION:
      Postnatal MgSO(4) infusion as above is safe and can improve short-term outcome in
      infants with severe birth asphyxia.

PMID- 12225551
TI  - Prevalence of gastro-esophageal reflux-related symptoms in Japanese infants.
AB  - BACKGROUND: To obtain precise information on the natural course of gastro
      esophageal reflux (GER)-related symptoms in Japanese children, we surveyed the
      prevalence of regurgitation or vomiting and other GER-related symptoms and
      complications in infants visiting for healthy baby check-ups. METHODS: We
      interviewed the mothers of 921 infants who had visited for baby check-ups at 1,
      4, 7 and 12 months after birth, about the number of regurgitation or vomiting
      episodes per day, other GER-related symptoms, milk volume, feeding interval, and
      the body position after feeding. RESULTS: Of 1-month-old infants, 47.1% had one
      or more regurgitation or vomiting episode per day. This proportion decreased to
      28.8% at 4 months old and 6.4% at 7 months old. The proportion of infants with
      three or more episodes of these symptoms per day showed a similar pattern. There
      was no significant difference in the prevalence of regurgitation or vomiting
      between breast-fed infants and formula-fed or mixed-feeding infants either at 1
      or 4 months of age. There was no significant difference in the bodyweight gain of
      3-month-old infants among those with various degrees of regurgitation. There was
      no significant difference in the frequency of regurgitation or vomiting episodes
      between infants placed in a vertical position and those placed in a horizontal
      position after feeding. No infant had a history of chronic coughing, wheezing,
      bleeding or other serious conditions. CONCLUSIONS: Regurgitation is a common
      symptom in Japanese infants and decreases spontaneously with age. The natural
      history of GER must be taken into consideration when deciding the treatment.

PMID- 12225552
TI  - Comparison of treatments of chronic hepatitis B in children with lamivudine and
      alpha-interferon combination and alpha-interferon alone.
AB  - BACKGROUND: The aim of this study was to compare the efficacy of the alpha
      interferon treatment with treatment using alpha-interferon and lamivudine in
      combination for cases of childhood chronic hepatitis B infection. METHODS:
      Patients were evaluated in two groups retrospectively. In group 1, 27 patients
      were simultaneously given alpha-interferon 2b 10 MU/m2, 3 days a week by s.c.
      injection plus lamivudine 4 mg/kg a day (maximum 100 mg) for 12 months. In group
      2, there were 13 patients who only received the same dosage of alpha-interferon
      and no lamivudine over the same period of time. RESULTS: In group 1 the initial
      mean value of alanine aminotransferase (ALT) was 121 +/- 66 IU/L and decreased to
      27.8 +/- 11.5 IU/L; in group 2, initial mean values of ALT was 129 +/- 46 IU/L
      and decreased to 60 +/- 6 IU/L at the end of the twelfth month of the therapy (P
      < 0.05). Hepatitis B virus DNA (HBV-DNA) clearance was obtained in all group 1
      patients and six of 13 patients in group 2 at the end of the therapy (P < 0.001).
      The rates of hepatitis B early (HBe) antigen clearance and anti-HBe
      seroconversion were 59 and 37% in group 1 and 46 and 30.7% in group 2 (P > 0.05).
      The number of patients with complete response was found to be 10 out of 27 (37%)
      in group 1 and four out of 13 cases (30.7%) in group 2, 6 months after the end of
      the therapy. There was no statistically significant difference between both
      groups (P > 0.05). CONCLUSION: alpha-Interferon and lamivudine combination
      therapy had a more beneficial effect than alpha-interferon monotherapy in
      normalization of ALT and clearance of HBV-DNA; however, the complete response
      rate at 6 months after the end of the therapy was not statistically significantly
      different between both groups.

PMID- 12225553
TI  - Aplastic anemia following hepatitis associated with echovirus 3.

PMID- 12225554
TI  - Intravenous prostacyclin combined with inhaled nitric oxide therapy for an infant
      with alveolar capillary dysplasia.

PMID- 12225555
TI  - Beraprost sodium for pulmonary hypertension with congenital heart disease.

PMID- 12225556
TI  - Case of insertion, inversion and deletion of chromosome 6.

PMID- 12225557
TI  - Inverted duplication/deletion of the short arm of chromosome 8 in two patients
      with tetralogy of Fallot.

PMID- 12225558
TI  - Crohn's disease in a child with Down syndrome.

PMID- 12225559
TI  - Infrequent voiding in nephrogenic diabetes insipidus as a cause of renal failure.

PMID- 12225560
TI  - Campylobacter coli bacteremia in an 11-year-old boy.

PMID- 12225561
TI  - Henoch-Schonlein purpura and pulmonary tuberculosis.

PMID- 12225562
TI  - Management of childhood diseases during the Byzantine period: V - hydrocephalus.
AB  - Hydrocephalus was a recognizable medical problem during the Byzantine period. In
      the medical texts of the time it was attributed to the pressure that was applied
      on the newborn's head during labour. The suggested treatments focused on the
      relief of the symptoms only and surgical methods were believed to be helpful in
      very rare cases.

PMID- 12225563
TI  - Management of childhood diseases during the Byzantine period: VI - ocular
      diseases.
AB  - Ocular manifestations were recognizable and are reported in the Byzantine medical
      treatises from the 4th to the 15th century AD. Herbal, mineral and chemical
      substances in the form of collyria were used by the Byzantine physicians for the
      treatment of ocular abnormalities and ophthalmic diseases of the childhood.
      Surgical intervention was not recommended at this age.

PMID- 12225564
TI  - Management of childhood diseases in the Byzantine period: VII - epilepsy.
AB  - Epilepsy was referred to as a serious medical problem with poor outcome by the
      Byzantine physicians. For the treatment they suggested herbal or animal
      substances in many different forms, but they stressed the importance of a proper
      diet. In their efforts to elucidate the mechanisms involved in the onset as well
      as the course of the disease they were influenced by the Hippocratic tradition of
      juices.

PMID- 12225567
TI  - Child protection for abused children: levels of response assessment, attachment
      relationships and systematic research synthesis.

PMID- 12225566
TI  - Child maltreatment 2002: recognition, reporting and risk.
AB  - BACKGROUND: Child abuse is a major cause of morbidity and mortality in the USA
      and in all other countries which have studied its incidence. It is the second
      leading cause of death of children in the USA. To decrease the incidence of child
      abuse and improve the welfare of children there must be international efforts to
      recognize, and report child abuse and to decrease those risk factors, which place
      children in jeopardy. In the USA, reports of child maltreatment have decreased
      each year since 1994 after nearly two decades of increase. The increase was
      associated with the passage of laws that mandated reporting child maltreatment
      and increased recognition of maltreatment. RESULTS: Several theories have been
      proposed to explain the decrease. These include: improved economy with decreased
      caretaker stress and more vulnerable children in day-care, imprisonment of
      offenders, treatment of victims to prevent reactive abuse, decreased use of
      corporal punishment, earlier recognition and reporting, prevention programs
      including home visitors and less corporal punishment in schools. If early
      recognition is to occur there must be clearly defined and uniform laws that
      define abuse and the significant consequences to mandated reporters for failure
      to report. The laws must be concise, understandable and contain medically based
      definitions of abuse. A bruise should be considered a significant injury. The use
      of an instrument on a child, for any reason should be reportable as abusive.
      Society must be taught that a child's head and its contents are particularly
      susceptible to trauma. Heads should not be slapped, shaken, or struck. The
      purpose of a report of suspect maltreatment should be to obtain services for
      families. Without proper services, abuse will reoccur and victims will become
      victimizers. Any sexual act, including pornography, involving a child who is
      unable to give consent constitutes reportable sexual abuse. Recognition of what
      constitutes abuse would be simplified if all countries adopted laws that forbid
      corporal punishment in schools and homes. Parenting education, which offers
      alternatives to the use of corporal punishment and anger and stress management
      skills, should be universal and begun in preschool. In the older child, topics
      would include conflict management tactics, mate selection, child development,
      child health, and pregnancy planning. DISCUSSION: Professional knowledge of child
      maltreatment is inadequate. This multidisciplinary topic must be incorporated
      into the undergraduate and graduate curricula in medicine and other professions
      dealing with children. Child victims are unable to represent themselves. In most
      other childhood diseases the parents rise up in arms to lobby for their
      children's rights and raise money for research, professional education and
      clinical services. In child maltreatment, government and private organizations
      must take on this task. The valuable resources of Federal Public Health Services
      become available when child maltreatment is declared to be a disease. Other
      countries should emulate countries that have eliminated corporal punishment of
      children. Countries that do not protect children from maltreatment including the
      ravages of war must be seen as perpetrators of child maltreatment and answerable
      to the international community. One may adhere to the adage that one is not one's
      brother's keeper. This should never be applied to children. As the world's most
      precious resource, we must be the keepers of all children.

PMID- 12225568
TI  - Protecting children's rights in a developing country.

PMID- 12225569
TI  - Child protection in the United Kingdom: pediatric perspective.

PMID- 12225570
TI  - Child abuse and neglect in Japan.

PMID- 12225574
TI  - Fish tale.
AB  - The draft sequence of the genome of the Japanese pufferfish has just been
      announced and the temptation to humor is great.

PMID- 12225577
TI  - Ranking genes with respect to differential expression.
AB  - BACKGROUND: In the pharmaceutical industry and in academia substantial efforts
      are made to make the best use of the promising microarray technology. The data
      generated by microarrays are more complex than most other biological data
      attracting much attention at this point. A method for finding an optimal test
      statistic with which to rank genes with respect to differential expression is
      outlined and tested. At the heart of the method lies an estimate of the false
      negative and false positive rates. Both investing in false positives and missing
      true positives lead to a waste of resources. The procedure sets out to minimise
      these errors. For calculation of the false positive and negative rates a
      simulation procedure is invoked. RESULTS: The method outperforms commonly used
      alternatives when applied to simulated data modelled after real cDNA array data
      as well as when applied to real oligonucleotide array data. In both cases the
      method comes out as the over-all winner. The simulated data are analysed both
      exponentiated and on the original scale, thus providing evidence of the ability
      to cope with normal and lognormal distributions. In the case of the real life
      data it is shown that the proposed method will tend to push the differentially
      expressed genes higher up on a test statistic based ranking list than the
      competitors. CONCLUSIONS: The approach of making use of information concerning
      both the false positive and false negative rates in the inference adds a useful
      tool to the toolbox available to scientists in functional genomics.

PMID- 12225576
TI  - Have microarrays failed to deliver for developmental biology?
AB  - Comprehensive microarrays covering large numbers of the predicted expressed
      transcripts for some invertebrates and vertebrates have been available for some
      time. Despite predictions that this technology will transform biology, to date
      there have been few published studies using microarrays to generate novel
      insights in developmental biology.

PMID- 12225578
TI  - Heart specific genes revealed by EST sampling.
AB  - BACKGROUND: Cardio-vascular diseases are the first cause of death worldwide,
      particularly in the developed countries; the identification of genes specifically
      expressed in the cardiac muscle is thus of major biomedical interest. In this
      study, we performed a comprehensive analysis of the expression profiles to
      identify genes over-expressed in the human adult heart using the public Expressed
      Sequence Tags (ESTs) database. The initial set of genes expressed in the heart
      was constructed by clustering and assembling ESTs from human adult heart cDNA
      libraries. Expression profiles were then generated for each of these genes by
      counting their cognate ESTs in all libraries. Differential expression was
      assessed by applying to these profiles a previously published statistical
      procedure. RESULTS: We identified 35 "cardiac specific" genes significantly over
      expressed in the heart, some of them exhibiting significant co-expressions. Some
      genes had clear functional association with the heart, and others had no
      previously recognized cardiac function. Of the 35 genes, 32 were mapped back onto
      the human genome sequence. According to OMIM, 5 genes were previously known as
      heart disease genes and one gene was located in the locus of a bleeding disorder.
      The analysis of the core promoter regions of our collection of "cardiac specific"
      genes provides the first list of putative regulatory elements associated with
      differential gene expression in the heart. CONCLUSION: This study shows that ESTs
      are still a powerful tool to identify differentially expressed genes: we
      presented a list of genes specifically expressed in the human heart, one of them
      being a candidate for a bleeding disorder. In addition, we provided the first set
      of putative regulatory elements, the combination of which appears correlated with
      heart-specific gene expression.

PMID- 12225579
TI  - Legume genomes and discoveries in symbiosis research.
AB  - A report on the First International Conference on Legume Genomics and Genetics:
      Translation to Crop Improvement, Minneapolis-St. Paul, USA, 2-6 June 2002.

PMID- 12225580
TI  - Sequence-based genomics.
AB  - A report on the Genome-Based Pathogen Biology meeting, Hinxton, UK, 7-10 July
      2002.

PMID- 12225581
TI  - When cell biology and neurobiology meet.
AB  - A report on the British Society for Cell Biology (BSCB) meeting on 'Cell Biology
      and Neurobiology: A Meeting for Martin Raff', London, UK, 3-5 July 2002.

PMID- 12225582
TI  - Human members of the eukaryotic protein kinase family.
AB  - BACKGROUND: Eukaryotic protein kinases (EPKs) constitute one of the largest
      recognized protein families represented in the human genome. EPKs, which are
      similar to each other in sequence, structure and biochemical properties, are
      important players in virtually every signaling pathway involved in normal
      development and disease. Near completion of projects to sequence the human genome
      and transcriptome provide an opportunity to identify and perform sequence
      analysis on a nearly complete set of human EPKs. RESULTS: Publicly available
      genetic sequence data were searched for human sequences that potentially
      represent EPK family members. After removal of duplicates, splice variants and
      pseudogenes, this search yielded 510 sequences with recognizable similarity to
      the EPK family. Protein sequences of putative EPK catalytic domains identified in
      the search were aligned, and a phonogram was constructed based on the alignment.
      Representative sequence records in GenBank were identified, and derived
      information about gene mapping and nomenclature was summarized. CONCLUSIONS: This
      work represents a nearly comprehensive census and early bioinformatics overview
      of the EPKs encoded in the human genome. Evaluation of the sequence relationships
      between these proteins contributes contextual information that enhances
      understanding of individual family members. This curation of human EPK sequences
      provides tools and a framework for the further characterization of this important
      class of enzymes.

PMID- 12225583
TI  - Computational discovery of sense-antisense transcription in the human and mouse
      genomes.
AB  - BACKGROUND: Overlapping but oppositely oriented transcripts have the potential to
      form sense-antisense perfect double-stranded (ds) RNA duplexes. Over recent
      years, the number and variety of examples of mammalian gene-regulatory phenomena
      in which endogenous dsRNA duplexes have been proposed or demonstrated to
      participate has greatly increased. These include genomic imprinting, RNA
      interference, translational regulation, alternative splicing, X-inactivation and
      RNA editing. We computationally mined public mouse and human expressed sequence
      tag (EST) databases to search for additional examples of bidirectionally
      transcribed genomic regions. RESULTS: Our bioinformatics approach identified over
      217 candidate overlapping transcriptional units, almost all of which are novel.
      From experimental validation of a subset of our predictions by orientation
      specific RT-PCR, we estimate that our methodology has a specificity of 84% or
      greater. In many cases, regions of sense-antisense overlap within the 5'- or 3'
      untranslated regions of a given transcript correlate with genomic patterns of
      mouse-human conservation. CONCLUSIONS: Our results, in conjunction with the
      literature, bring the total number of predicted and validated examples of
      overlapping but oppositely oriented transcripts to over 300. Several of these
      cases support the hypothesis that a subset of the instances of substantial mouse
      human conservation in the 5' and 3' UTRs of transcripts might be explained in
      part by functionality of an overlapping transcriptional unit.

PMID- 12225585
TI  - Design and implementation of microarray gene expression markup language (MAGE
      ML).
AB  - BACKGROUND: Meaningful exchange of microarray data is currently difficult because
      it is rare that published data provide sufficient information depth or are even
      in the same format from one publication to another. Only when data can be easily
      exchanged will the entire biological community be able to derive the full benefit
      from such microarray studies. RESULTS: To this end we have developed three key
      ingredients towards standardizing the storage and exchange of microarray data.
      First, we have created a minimal information for the annotation of a microarray
      experiment (MIAME)-compliant conceptualization of microarray experiments modeled
      using the unified modeling language (UML) named MAGE-OM (microarray gene
      expression object model). Second, we have translated MAGE-OM into an XML-based
      data format, MAGE-ML, to facilitate the exchange of data. Third, some of us are
      now using MAGE (or its progenitors) in data production settings. Finally, we have
      developed a freely available software tool kit (MAGE-STK) that eases the
      integration of MAGE-ML into end users' systems. CONCLUSIONS: MAGE will help
      microarray data producers and users to exchange information by providing a common
      platform for data exchange, and MAGE-STK will make the adoption of MAGE easier.

PMID- 12225584
TI  - Gene-expression profile comparisons distinguish seven organs of maize.
AB  - BACKGROUND: A maize array was fabricated with 5,376 unique expressed sequence tag
      (EST) clones sequenced from 4-day-old roots, immature ears and adult organ cDNA
      libraries. To elucidate organ relationships, relative mRNA levels were quantified
      by hybridization with embryos, three maize vegetative organs (leaf blades, leaf
      sheaths and roots) from multiple developmental stages, husk leaves and two types
      of floral organs (immature ears and silks). RESULTS: Clustering analyses of the
      hybridization data suggest that maize utilizes both the PEPCK and NADP-ME C(4)
      photosynthetic routes as genes in these pathways are co-regulated. Husk RNA has a
      gene-expression profile more similar to floral organs than to vegetative leaves.
      Only 7% of the genes were highly organ specific, showing over a fourfold
      difference in at least one of 12 comparisons and 37% showed a two- to fourfold
      difference. The majority of genes were expressed in diverse organs with little
      difference in transcript levels. Cross-hybridization among closely related genes
      within multigene families could obscure tissue specificity. As a first step in
      elucidating individual gene-expression patterns, we show that 45-nucleotide oligo
      probes produce signal intensities and signal ratios comparable to PCR probes on
      the same matrix. CONCLUSIONS: Gene-expression profile studies with cDNA
      microarrays provide a new molecular tool for defining plant organs and their
      relationships and for discovering new biological processes in silico. cDNA
      microarrays are insufficient for differentiating recently duplicated genes. Gene
      specific oligo probes printed along with cDNA probes can query individual gene
      expression profiles and gene families simultaneously.

PMID- 12225586
TI  - NEAT: a domain duplicated in genes near the components of a putative Fe3+
      siderophore transporter from Gram-positive pathogenic bacteria.
AB  - BACKGROUND: Iron uptake from the host is essential for bacteria that infect
      animals. To find potential targets for drugs active against pathogenic bacteria,
      we have searched all completely sequenced genomes of pathogenic bacteria for
      genes relevant for iron transport. RESULTS: We identified a protein domain that
      appears in variable copy number in bacterial genes that are usually in the
      vicinity of a putative Fe3+ siderophore transporter. Accordingly, we have denoted
      this domain NEAT for 'near transporter'. Most of the bacterial species containing
      this domain are pathogenic. Sequence features indicate that the domain is
      anchored to the extracellular side of the membrane. The domain seems to be under
      high selective pressure for rapid independent duplications that are typical of
      sequences involved in signaling and binding. CONCLUSIONS: The NEAT domain might
      be functionally related to iron transport. The taxonomic specificity of this
      domain and its predicted extracellular position could make it an interesting
      target for designing new drugs against some highly pathogenic bacteria.

PMID- 12225588
TI  - Fine mapping in tomato using microsynteny with the Arabidopsis genome: the
      Diageotropica (Dgt) locus.
AB  - BACKGROUND: The Arabidopsis thaliana genome sequence provides a catalog of
      reference genes applicable to comparative microsynteny analysis of other species,
      facilitating map-based cloning in economically important crops. We have applied
      such an analysis to the tomato expressed sequence tag (EST) database to expedite
      high-resolution mapping of the Diageotropica (Dgt) gene within the distal end of
      chromosome 1 in tomato (Lycopersicon esculentum). RESULTS: A BLAST search of the
      Arabidopsis database with nucleotide sequences of markers that flank the tomato
      dgt locus revealed regions of microsynteny between the distal end of chromosome 1
      in tomato, two regions of Arabidopsis chromosome 4, and one on chromosome 2.
      Tomato ESTs homeologous to Arabidopsis gene sequences within those regions were
      converted into co-dominant molecular markers via cleaved amplified polymorphic
      sequence (CAPS) analysis and scored against an informative backcross mapping
      population. Six new microsyntenic EST (MEST) markers were rapidly identified in
      the dgt region, two of which further defined the placement of the Dgt gene and
      permitted the selection of a candidate tomato bacterial artificial chromosome
      clone for sequence analysis. CONCLUSIONS: Microsynteny-based comparative mapping
      combined with CAPS analysis of recombinant plants rapidly and economically
      narrowed the dgt mapping region from 0.8 to 0.15 cM. This approach should
      contribute to developing high-density maps of molecular markers to target
      specific regions for positional cloning and marker-assisted selection in a
      variety of plants.

PMID- 12225587
TI  - A new non-linear normalization method for reducing variability in DNA microarray
      experiments.
AB  - BACKGROUND: Microarray data are subject to multiple sources of variation, of
      which biological sources are of interest whereas most others are only
      confounding. Recent work has identified systematic sources of variation that are
      intensity-dependent and non-linear in nature. Systematic sources of variation are
      not limited to the differing properties of the cyanine dyes Cy(5) and Cy(3) as
      observed in cDNA arrays, but are the general case for both oligonucleotide
      microarray (Affymetrix GeneChips) and cDNA microarray data. Current normalization
      techniques are most often linear and therefore not capable of fully correcting
      for these effects. RESULTS: We present here a simple and robust non-linear method
      for normalization using array signal distribution analysis and cubic splines.
      These methods compared favorably to normalization using robust local-linear
      regression (lowess). The application of these methods to oligonucleotide arrays
      reduced the relative error between replicates by 5-10% compared with a standard
      global normalization method. Application to cDNA arrays showed improvements over
      the standard method and over Cy(3)-Cy(5) normalization based on dye-swap
      replication. In addition, a set of known differentially regulated genes was
      ranked higher by the t-test. In either cDNA or Affymetrix technology, signal
      dependent bias was more than ten times greater than the observed print-tip or
      spatial effects. CONCLUSIONS: Intensity-dependent normalization is important for
      both high-density oligonucleotide array and cDNA array data. Both the regression
      and spline-based methods described here performed better than existing linear
      methods when assessed on the variability of replicate arrays. Dye-swap
      normalization was less effective at Cy(3)-Cy(5) normalization than either
      regression or spline-based methods alone.

PMID- 12225589
TI  - PRESTA: associating promoter sequences with information on gene expression.
AB  - BACKGROUND: Large sets of well-characterized promoter sequences are required to
      facilitate the understanding of promoter architecture. The major sequence
      databases are a prospective source of upstream regulatory regions, but suffer
      from inaccurate annotation. The software tool PRESTA (PRomoter EST Association)
      presented in this study is designed for efficient recovery of characterized and
      partially verified promoters from GenBank and EMBL libraries. RESULTS: The PRESTA
      algorithm examines the putative GenBank/EMBL promoters and automatically removes
      most of the poorly annotated entries. The remaining records are connected to
      expressed sequence tags (ESTs) through a high-stringency BLAST search. The
      frequency and source of recovered ESTs provide an estimate of the activity and
      expression pattern of the promoter, and the ESTs' 5' ends assist in transcription
      start-site verification. The PRESTA database provides easy access to non
      redundant upstream regulatory regions recently extracted by the PRESTA algorithm.
      The current size of this resource is 552 human and 241 mouse promoters.
      Surprisingly, no overlap between the PRESTA database and the Eukaryotic Promoter
      Database (EPD) was detected by sequence comparison. CONCLUSIONS: The PRESTA
      algorithm demonstrates the principle of promoter verification by mapping EST 5'
      ends. The publicly available PRESTA database collects hundreds of characterized
      and partially verified promoter sequences and is complementary to other promoter
      databases.

PMID- 12225591
TI  - Sushi gets serious: the draft genome sequence of the pufferfish Fugu rubripes.
AB  - The publication of the Fugu rubripes draft genome sequence will take this fish
      from culinary delicacy to potent tool in deciphering the mysteries of human
      genome function.

PMID- 12225590
TI  - Dynamic diversity of the tryptophan pathway in chlamydiae: reductive evolution
      and a novel operon for tryptophan recapture.
AB  - BACKGROUND: Complete genomic sequences of closely related organisms, such as the
      chlamydiae, afford the opportunity to assess significant strain differences
      against a background of many shared characteristics. The chlamydiae are
      ubiquitous intracellular parasites that are important pathogens of humans and
      other organisms. Tryptophan limitation caused by production of interferon-gamma
      by the host and subsequent induction of indoleamine dioxygenase is a key aspect
      of the host-parasite interaction. It appears that the chlamydiae have learned to
      recognize tryptophan depletion as a signal for developmental remodeling. The
      consequent non-cultivable state of persistence can be increasingly equated to
      chronic disease conditions. RESULTS: The genes encoding enzymes of tryptophan
      biosynthesis were the focal point of this study. Chlamydophila psittaci was found
      to possess a compact operon containing PRPP synthase, kynureninase, and genes
      encoding all but the first step of tryptophan biosynthesis. All but one of the
      genes exhibited translational coupling. Other chlamydiae (Chlamydia trachomatis,
      C. muridarum and Chlamydophila pneumoniae) lack genes encoding PRPP synthase,
      kynureninase, and either lack tryptophan-pathway genes altogether or exhibit
      various stages of reductive loss. The origin of the genes comprising the trp
      operon does not seem to have been from lateral gene transfer. CONCLUSIONS: The
      factors that accommodate the transition of different chlamydial species to the
      persistent (chronic) state of pathogenesis include marked differences in
      strategies deployed to obtain tryptophan from host resources. C. psittaci appears
      to have a novel mechanism for intercepting an early intermediate of tryptophan
      catabolism and recycling it back to tryptophan. In effect, a host-parasite
      metabolic mosaic has evolved for tryptophan recycling.

PMID- 12225592
TI  - Evolutionary origins of the endosperm in flowering plants.
AB  - The evolutionary origin of double fertilization and the resultant endosperm
      tissue in flowering plants remains a puzzle, despite over a century of research.
      The recent resurgence of approaches to evolutionary developmental biology
      combining comparative biology with phylogenetics provides new understanding of
      endosperm origins.

PMID- 12225594
TI  - The International Sepsis Forum's controversies in sepsis: how will sepsis be
      treated in 2051?

PMID- 12225595
TI  - Immunodepression in the surgical patient and increased susceptibility to
      infection.

PMID- 12225593
TI  - The retinoblastoma family: twins or distant cousins?
AB  - The destiny of a cell--whether it undergoes division, differentiation or death-
      results from an intricate balance of many regulators, including oncoproteins,
      tumor-suppressor proteins and cell-cycle-associated proteins. One of the better
      studied tumor suppressors is the retinoblastoma protein, known as pRb or p105.
      Two recently identified proteins, pRb2/p130 and p107, show structural and
      functional similarities to pRb, and these proteins and their orthologs make up
      the retinoblastoma (Rb) family. Members of the family have been found in animals
      and plants, and a related protein is known in the alga Chlamydomonas. Members of
      the Rb family are bound and inactivated by viral proteins and, in turn, bind
      cellular transcription factors and repress their function, and can also form
      complexes with cyclins and cyclin-dependent kinases and with histone
      deacetylases. They are found in the nucleus and their subnuclear localization
      depends on binding to the nuclear matrix. Members of the family form part of a
      signal-transduction pathway called the Rb pathway, which is important in cell
      cycle regulation and have roles in growth suppression, differentiation and
      apoptosis in different organisms and cell types.

PMID- 12225596
TI  - Gut oxygenation in sepsis: still a matter of controversy?

PMID- 12225597
TI  - Lactate: A key metabolite in the intercellular metabolic interplay.

PMID- 12225598
TI  - Pro/con clinical debate: do colloids have advantages over crystalloids in
      paediatric sepsis?

PMID- 12225599
TI  - Endotoxemia in critically ill patients: why a reliable test could be beneficial.

PMID- 12225600
TI  - ICU Cornerstone: changing our view of blood transfusions.

PMID- 12225601
TI  - Looking beyond 28-day all-cause mortality.

PMID- 12225602
TI  - Recently published papers: we are what we eat?

PMID- 12225603
TI  - Clinical review: immunodepression in the surgical patient and increased
      susceptibility to infection.
AB  - Several studies indicate that organ failure is the leading cause of death in
      surgical patients. An excessive inflammatory response followed by a dramatic
      paralysis of cell-mediated immunity following major surgery appears to be
      responsible for the increased susceptibility to subsequent sepsis. In view of
      this, most of the scientific and medical research has been directed towards
      measuring the progression and inter-relationship of mediators following major
      surgery. Furthermore, the effect of those mediators on cell-mediated immune
      responses has been studied. This article will focus on the effect of blood loss
      and surgical injury on cell-mediated immune responses in experimental studies
      utilizing models of trauma and hemorrhagic shock, which have defined effects on
      the immunoinflammatory response. Subsequently these findings will be correlated
      with data generated from surgical patients. The results of these studies may
      generate new approaches for the treatment of immunodepression following major
      surgery, thus reducing the susceptibility to infection and increasing the
      survival rate of the critical ill surgical patient.

PMID- 12225604
TI  - Clinical review: splanchnic ischaemia.
AB  - Inadequate splanchnic perfusion is associated with increased morbidity and
      mortality, particularly if liver dysfunction coexists. Heart failure, increased
      intra-abdominal pressure, haemodialysis and the presence of obstructive sleep
      apnoea are among the multiple clinical conditions that are associated with
      impaired splanchnic perfusion in critically ill patients. Total liver blood flow
      is believed to be relatively protected when gut blood flow decreases, because
      hepatic arterial flow increases when portal venous flow decreases (the hepatic
      arterial buffer response [HABR]). However, there is evidence that the HABR is
      diminished or even abolished during endotoxaemia and when gut blood flow becomes
      very low. Unfortunately, no drugs are yet available that increase total hepato
      splanchnic blood flow selectively and to a clinically relevant extent. The
      present review discusses old and new concepts of splanchnic vasoregulation from
      both experimental and clinical viewpoints. Recently published trials in this
      field are discussed.

PMID- 12225605
TI  - Clinical review: use of vancomycin in haemodialysis patients.
AB  - Following intravenous administration, vancomycin is poorly metabolized and is
      mainly excreted unchanged in urine. Total body clearance is thus dependent on the
      kidney, and is correlated with glomerular filtration rate and creatinine
      clearance. Accumulation of vancomycin in patients with renal insufficiency may
      therefore occur, and this may lead to toxic side effects if dosage is not
      modified according to the degree of renal failure. Furthermore, vancomycin easily
      diffuses through dialysis membranes. The aim of the present review is to
      establish guidelines for handling this drug in such patients. We indicate how and
      when plasma concentrations of vancomycin should be determined in dialysis
      patients.

PMID- 12225606
TI  - Bench-to-bedside review: glucose production from the kidney.
AB  - Data obtained from net organ balance studies of glucose production lead to the
      classic view according to which glucose homeostasis is mainly ensured by the
      liver, and renal glucose production only plays a significant role during acidosis
      and prolonged starvation. Renal glucose release and uptake, as well as the
      participation of gluconeogenic substrates in renal gluconeogenesis, were recently
      re-evaluated using systemic and renal arteriovenous balance of substrates in
      combination with deuterated glucose dilution. Data obtained using these methods
      lead one to reconsider the magnitude of renal glucose production as well as its
      role in various physiological and pathological circumstances. These findings now
      conduce one to consider that renal gluconeogenesis substantially participates in
      postabsorptive glucose production, and that its role in glucose homeostasis is of
      first importance.

PMID- 12225607
TI  - Bench-to-bedside review: lactate and the kidney.
AB  - The native kidney has a major role in lactate metabolism. The renal cortex
      appears to be the major lactate-consuming organ in the body after the liver.
      Under conditions of exogenous hyperlactatemia, the kidney is responsible for the
      removal of 25-30% of all infused lactate. Most of such removal is through lactate
      metabolism rather than excretion, although under conditions of marked
      hyperlactatemia such excretion can account for approximately 10-12% of renal
      lactate disposal. Indeed, nephrectomy results in an approximately 30% decrease in
      exogenous lactate removal. Importantly and differently from the liver, however,
      the kidney's ability to remove lactate is increased by acidosis. While acidosis
      inhibits hepatic lactate metabolism, it increases lactate uptake and utilization
      via gluconeogenesis by stimulating the activity of phospho-enolpyruvate
      carboxykinase. The kidney remains an effective lactate-removing organ even during
      endotoxemic shock. The artificial kidney also has a profound effect on lactate
      balance. If lactate-buffered fluids are used in patients who require continuous
      hemofiltration and who have pretreatment hyperlactatemia, the serum lactate
      levels can significantly increase. In some cases, this increase can result in an
      exacerbation of metabolic acidosis. If bicarbonate-buffered replacement fluids
      are used, a significant correction of the acidosis or acidemia can also be
      achieved. The clinician needs to be aware of these renal effects on lactate
      levels to understand the pathogenesis of hyperlactatemia in critically ill
      patients, and to avoid misinterpretations and unnecessary or inappropriate
      diagnostic or therapeutic activities.

PMID- 12225608
TI  - Bench-to-bedside review: lactate and the lung.
AB  - The ability of the isolated lung tissue to take up glucose and to release lactate
      is potentially similar to that of other body tissues. Nonetheless, when lung
      lactate exchange was assess in vivo in normal humans, no measurable lactate
      production could be detected. Lung lactate production may become clinically
      evident in disease states especially in the patients with acute lung injury or
      with acute respiratory distress syndrome. Potential mechanisms of lactate
      production by the injured lung may include not only the onset of anaerobic
      metabolism in hypoxic zones, but also direct cytokine effects on pulmonary cells
      and an accelerated glucose metabolism in both the parenchymal and the
      inflammatory cells infiltrating lung tissue. In addition, as skeletal muscle,
      lung tissue may show metabolic adaptations in response to systemic mediators and
      may contribute to the systemic metabolic response to severe illness even in the
      absence of direct tissue abnormalities.

PMID- 12225610
TI  - Statistics review 4: sample size calculations.
AB  - The present review introduces the notion of statistical power and the hazard of
      under-powered studies. The problem of how to calculate an ideal sample size is
      also discussed within the context of factors that affect power, and specific
      methods for the calculation of sample size are presented for two common
      scenarios, along with extensions to the simplest case.

PMID- 12225609
TI  - Bench-to-bedside review: a possible resolution of the glucose paradox of cerebral
      ischemia.
AB  - The glucose paradox of cerebral ischemia (namely, the aggravation of delayed
      ischemic neuronal damage by preischemic hyperglycemia) has been promoted as proof
      that lactic acidosis is a detrimental factor in this brain disorder. Recent
      studies, both in vitro and in vivo, have demonstrated lactate as an excellent
      aerobic energy substrate in the brain, and possibly a crucial one immediately
      postischemia. Moreover, evidence has been presented that refutes the lactic
      acidosis hypothesis of cerebral ischemia and thus has questioned the traditional
      explanation given for the glucose paradox. An alternative explanation for the
      aggravating effect of preischemic hyperglycemia on the postischemic outcome has
      consequently been offered, according to which glucose loading induces a short
      lived elevation in the release of glucocorticoids. When an episode of cerebral
      ischemia in the rat coincided with glucose-induced elevated levels of
      corticosterone (CT), the main rodent glucocorticoid, an aggravation of the
      ischemic outcome was observed. Both the blockade of CT elevation by chemical
      adrenalectomy with metyrapone or the blockade of CT receptors in the brain with
      mifepristone (RU486) negated the aggravating effect of preischemic hyperglycemia
      on the postischemic outcome.

PMID- 12225611
TI  - Measurement of endotoxin activity in critically ill patients using whole blood
      neutrophil dependent chemiluminescence.
AB  - BACKGROUND: Lipopolysaccharide (endotoxin) from the cell wall of Gram-negative
      bacteria is a potent trigger for the release of host-derived inflammatory
      mediators. The relationship between endotoxaemia, Gram-negative infection and the
      clinical syndrome of sepsis has been difficult to establish, in part because of
      the limitations of available endotoxin assays. METHODS: We performed an
      observational cohort study in critically ill patients in the medical/surgical
      intensive care unit (ICU) of a tertiary care hospital. Whole blood endotoxin
      levels on the day of ICU admission were measured using a novel chemiluminescent
      assay--the endotoxin activity assay (EAA)--and the chromogenic modification of
      the limulus amoebocyte lysate (LAL) assay. RESULTS: We studied 74 consecutive
      admissions. Endotoxin levels were higher in patients with a diagnosis of sepsis
      (470 +/- 57 pg/ml) than in patients admitted with a diagnosis other than sepsis
      (157 +/- 140 pg/ml; P < 0.001). Endotoxaemia was significantly associated with
      Gram-negative infection (P < 0.05); no patient with a Gram-negative infection had
      an endotoxin level below 50 pg/ml. White blood cell counts of patients with EAA
      detected endotoxaemia were significantly higher (15.7 +/- 9.1 x 10(9) cells/l for
      endotoxaemic patients versus 10.8 +/- 6.2 x 10(9) cells/l for patients without
      endotoxaemia; P < 0.05). CONCLUSION: Endotoxaemia is associated with Gram
      negative infection from any source, and with a diagnosis of sepsis and
      leukocytosis. These correlations were not apparent using the LAL method. The EAA
      may be a useful diagnostic tool for the investigation of invasive Gram-negative
      infection and incipient sepsis.

PMID- 12225612
TI  - Quality of life effects of antithrombin III in sepsis survivors: results from the
      KyberSept trial [ISRCTN22931023].
AB  - INTRODUCTION: Treatment of sepsis is aimed at increasing both the duration and
      quality of survival. A long-term focus on quality of life (QoL) in clinical trial
      evaluations of sepsis care should be a priority. METHOD: QoL data were used to
      evaluate the effects of intravenous antithrombin III treatment for severe sepsis
      measured for up to 90 days during the follow-up phase of the KyberSept phase III
      clinical trial. A visual analog scale and a Karnofsky scale were used to measure
      physical, psychologic, and social QoL at regular intervals. Changes from baseline
      between placebo and antithrombin III groups were assessed using Wilcoxon
      statistical tests, with additional analyses by severity of illness and admitting
      diagnosis. RESULTS: Among all sepsis survivors in the trial, there was a
      significant advantage on some attributes of QoL in the antithrombin III subgroup
      of patients who did not receive heparin as compared with the corresponding
      placebo group. DISCUSSION: The present study represents the first attempt to
      evaluate patient QoL over a relatively long period in a large, randomized,
      placebo-controlled sepsis trial. Over a 90-day period, survivors of severe sepsis
      receiving antithrombin III experienced significant improvements as compared with
      placebo on several attributes of QoL. In conclusion, the present study
      demonstrated that clinical improvements over an extended time period with
      antithrombin III were complemented by improvements in QoL, particularly in social
      and psychologic functioning, in many patients.

PMID- 12225613
TI  - The effects of IgM-enriched immunoglobulin preparations in patients with severe
      sepsis [ISRCTN28863830].
AB  - INTRODUCTION: In this prospective, randomized controlled study, we aimed to
      evaluate the effect of IgM-enriched immunoglobulin treatment on progression of
      organ failure and septic shock in patients with severe sepsis. MATERIALS AND
      METHODS: Forty-two patients with severe sepsis were enrolled in the study.
      Patients in the study group (n = 21) received an intravenous immunoglobulin
      preparation (Pentaglobin in addition to standard therapy. Pentaglobin therapy was
      commenced on the day of diagnosis of severe sepsis: 5 ml/kg per day Pentaglobin
      (38 g/l IgG, 6 g/l IgM, and 6 g/l IgA) was infused over 6 hours and repeated for
      3 consecutive days. Patients in the control group (n = 18) received standard
      sepsis therapy, but no immunoglobulin administration. Blood samples for
      procalcitonin (PCT) measurements were taken daily for 8 days. Severity of
      critical illness and development of organ failure were assessed by obtaining
      daily acute physiological and chronic health evaluation (APACHE) II and
      sequential organ failure assessment (SOFA) scores. RESULTS AND DISCUSSION:
      Procalcitonin levels showed a statistically significant decrease in the
      Pentaglobin group (P < 0.001); however, an improvement in SOFA scores could not
      be demonstrated. Procalcitonin levels and SOFA scores did not change
      significantly in the control group. Septic shock incidence (38% versus 57%) and
      28-day mortality rate (23.8% versus 33.3%) were found to be similar between the
      Pentaglobin and control groups. The evaluation of serial APACHE II scores did not
      demonstrate a difference between Pentaglobin and control groups either.
      CONCLUSION: Present data could not demonstrate any beneficial effects of
      polyclonal immunoglobulin preparation Pentaglobin on organ morbidity, septic
      shock incidence and mortality rate in patients with severe sepsis.

PMID- 12225614
TI  - Expression of the C5a receptor (CD88) on granulocytes and monocytes in patients
      with severe sepsis.
AB  - INTRODUCTION: Treatment of patients with severe sepsis with agents antagonising
      the effects of C5a has been proposed based on beneficial effects in animal
      experiments and in vitro studies demonstrating upregulation of the C5a receptor
      (CD88) on granulocytes by endotoxin. MATERIALS AND METHODS: CD88 expression on
      leukocytes from 12 patients with severe sepsis or septic shock was analysed by
      flow cytometer, and serum complement factors C3a and C5b-9 were measured by
      enzyme immunoassay techniques. RESULTS: The granulocyte CD88 expression on day 1
      was lowered (36; range, 2-59) in comparison with controls (63; range, 25-88) (P <
      0.001), despite complement activation, while the monocyte CD88 expression was
      unchanged. The receptor reduction correlated significantly to the APACHE II score
      (r2 = 0.35, P < 0.05). The recovery of CD88 expression was slow. DISCUSSION: In
      contrast to the findings in animals, it is concluded that granulocyte CD88
      expression is reduced at the time when the diagnosis of severe sepsis or septic
      shock can clinically be made. The reason for this needs further investigation but
      it may be due to a previous complement activation or to cytokine effects.

PMID- 12225615
TI  - Need for critical care in gynaecology: a population-based analysis.
AB  - INTRODUCTION: The purpose of this study was to note potential gynaecological risk
      factors leading to intensive care and to estimate the frequency, costs and
      outcome of management. MATERIALS AND METHODS: In a cross-sectional study of
      intensive care admissions in Kuopio from March 1993 to December 2000, 23
      consecutive gynaecological patients admitted to a mixed medical-surgical
      intensive care unit (ICU) were followed. We recorded demographics, admitting
      diagnoses, scores on the Acute Physiological and Chronic Health Evaluation
      (APACHE) II, clinical outcome and treatment costs. RESULTS: The overall need for
      intensive care was 2.3 per 1000 women undergoing major surgery during the study
      period. Patients were 55.4 +/- 16.9 (mean +/- SD) years old, with a mean APACHE
      II score of 14.07 (+/- 5.57). The most common diagnoses at admission were
      postoperative haemorrhage (43%), infection (39%) and cardiovascular disease
      (30%). The duration of stay in the ICU was 4.97 (+/- 9.28) (range 1-42) days and
      the mortality within 6 months was 26%, although the mortality in the ICU was 0%.
      The total cost of intensive care was approximately 7044 US dollars per patient.
      CONCLUSIONS: Very few gynaecological patients develop complications requiring
      intensive care. The presence of gynaecological malignancy and pre-existing
      medical disorders are clinically useful predictors of eventual outcome, but many
      cases occur in women with a low risk and this implies that the risk is relevant
      to all procedures. Further research is needed to determine effective preventive
      approaches.

PMID- 12225617
TI  - Patient attitudes toward using computers to improve health services delivery.
AB  - BACKGROUND: The aim of this study was to examine the acceptability of point of
      care computerized prompts to improve health services delivery among a sample of
      primary care patients. METHODS: Primary data collection. Cross-sectional survey.
      Patients were surveyed after their visit with a primary care provider. Data were
      obtained from patients of ten community-based primary care practices in the
      spring of 2001. RESULTS: Almost all patients reported that they would support
      using a computer before each visit to prompt their doctor to: "do health
      screening tests" (92%), "counsel about health behaviors (like diet and exercise)"
      (92%) and "change treatments for health conditions" (86%). In multivariate
      testing, the only variable that was associated with acceptability of the point of
      care computerized prompts was patient's confidence in their ability to answer
      questions about their health using a computer (beta = 0.39, p =.001). Concerns
      about data security were expressed by 36.3% of subjects, but were not related to
      acceptability of the prompts. CONCLUSIONS: Support for using computers to
      generate point of care prompts to improve quality-oriented processes of care was
      high in our sample, but may be contingent on patients feeling familiar with their
      personal medical history.

PMID- 12225618
TI  - Predictors of positive health in disability pensioners: a population-based
      questionnaire study using Positive Odds Ratio.
AB  - BACKGROUND: Determinants of ill-health have been studied far more than
      determinants of good and improving health. Health promotion measures are
      important even among individuals with chronic diseases. The aim of this study was
      to find predictors of positive subjective health among disability pensioners
      (DPs) with musculoskeletal disorders. METHODS: Two questionnaire surveys were
      performed among 352 DPs with musculoskeletal disorders. Two groups were defined:
      DPs with positive health and negative health, respectively. In consequence with
      the health perspective in this study the conception Positive Odds Ratio was
      defined and used in the logistic regression analyses instead of the commonly used
      odds ratio. RESULTS: Positive health was associated with age > or = 55 years, not
      being an immigrant, not having fibromyalgia as the main diagnosis for granting an
      early retirement, no regular use of analgesics, a high ADL capacity, a positive
      subjective health preceding the study period, and good quality of life.
      CONCLUSION: Positive odds ratio is a concept well adapted to theories of health
      promotion. It can be used in relation to positive outcomes instead of risks.
      Suggested health promotion and secondary prevention efforts among individuals
      with musculoskeletal disorders are 1) to avoid a disability pension for
      individuals <55 years of age; if necessary, to make sure rehabilitation actions
      continue, 2) to increase efforts to support immigrants to adjust to circumstances
      connected to ill-health and retirement, 3) to pay special attention to
      individuals with fibromyalgia and other general pain disorders, and 4) to
      strengthen ADL activities to support an independent active life among disability
      pensioners.

PMID- 12225619
TI  - Mutational analyses of the signals involved in the subcellular location of DSCR1.
AB  - BACKGROUND: Down syndrome is the most frequent genetic disorder in humans. Rare
      cases involving partial trisomy of chromosome 21 allowed a small chromosomal
      region common to all carriers, called Down Syndrome Critical Region (DSCR), to be
      determined. The DSCR1 gene was identified in this region and is expressed
      preferentially in the brain, heart and skeletal muscle. Recent studies have shown
      that DSCR1 belongs to a family of proteins that binds and inhibits calcineurin, a
      serine-threonine phosphatase. The work reported on herein consisted of a study of
      the subcellular location of DSCR1 and DSCR1-mutated forms by fusion with a green
      fluorescent protein, using various cell lines, including human. RESULTS: The
      protein's location was preferentially nuclear, independently of the isoform, cell
      line and insertion in the GFP's N- or C-terminal. A segment in the C-terminal,
      which is important in the location of the protein, was identified by deletion. On
      the other hand, site-directed mutational analyses have indicated the involvement
      of some serine and threonine residues in this event. CONCLUSION: In this paper,
      we discuss the identification of amino acids which can be important for
      subcellular location of DSCR1. The involvement of residues that are prone to
      phosphorylation suggests that the location and function of DSCR1 may be regulated
      by kinases and/or phosphatases.

PMID- 12225620
TI  - Prediction of MHC class I binding peptides, using SVMHC.
AB  - BACKGROUND: T-cells are key players in regulating a specific immune response.
      Activation of cytotoxic T-cells requires recognition of specific peptides bound
      to Major Histocompatibility Complex (MHC) class I molecules. MHC-peptide
      complexes are potential tools for diagnosis and treatment of pathogens and
      cancer, as well as for the development of peptide vaccines. Only one in 100 to
      200 potential binders actually binds to a certain MHC molecule, therefore a good
      prediction method for MHC class I binding peptides can reduce the number of
      candidate binders that need to be synthesized and tested. RESULTS: Here, we
      present a novel approach, SVMHC, based on support vector machines to predict the
      binding of peptides to MHC class I molecules. This method seems to perform
      slightly better than two profile based methods, SYFPEITHI and HLA_BIND. The
      implementation of SVMHC is quite simple and does not involve any manual steps,
      therefore as more data become available it is trivial to provide prediction for
      more MHC types. SVMHC currently contains prediction for 26 MHC class I types from
      the MHCPEP database or alternatively 6 MHC class I types from the higher quality
      SYFPEITHI database. The prediction models for these MHC types are implemented in
      a public web service available at http://www.sbc.su.se/svmhc/. CONCLUSIONS:
      Prediction of MHC class I binding peptides using Support Vector Machines, shows
      high performance and is easy to apply to a large number of MHC class I types. As
      more peptide data are put into MHC databases, SVMHC can easily be updated to give
      prediction for additional MHC class I types. We suggest that the number of
      binding peptides needed for SVM training is at least 20 sequences.

PMID- 12225621
TI  - Cervical cancer knowledge and screening in Accra, Ghana.

PMID- 12225623
TI  - Toward optimal health: the experts discuss antibiotic therapy in primary care.
      Interview by Jodi Godfrey Meisler.

PMID- 12225624
TI  - Interdisciplinary research is key to understanding sex differences: report from
      the Society for Women's Health Research Meeting on understanding the biology of
      sex differences.
AB  - Progress in sex-based biology, the study of biological and behavioral differences
      between males and females, and the impact of those differences on health and
      disease will require collaboration across research disciplines and medical
      specialties and among all research approaches, from molecular biology to
      epidemiology. The importance of sex-based biology to healthcare necessitates a
      bench-to-bedside approach that is built on integration of research findings from
      studies at the cellular level, in animals, and in human subjects. Barriers to
      interdisciplinary collaborations are being addressed in a variety of ways by
      public and private funders. The J.D. and C.T. MacArthur Foundation supports
      interdisciplinary research networks that address broad questions in health and
      behavior. The National Institute of Mental Health supports cross-disciplinary
      research networks investigating the hypothalamic-pituitary-adrenal network. The
      National Institute of Child Health and Human Development offers grants for
      Building Interdisciplinary Research Careers in Women's Health. The National
      Science Foundation Directorate for Biological Sciences sponsors Research
      Coordination Networks in Biological Sciences. Among the challenges faced by
      interdisciplinary research programs are appropriate peer review, career
      advancement for young investigators with interdisciplinary training, and
      acceptance of interdisciplinary research reports by high-quality scientific
      publications.

PMID- 12225625
TI  - Postmenopausal estrogen and increased risk of clinical osteoarthritis at the hip,
      hand, and knee in older women.
AB  - OBJECTIVE: We examined postmenopausal estrogen (PME) use and prevalence of
      clinical osteoarthritis (OA) at the hand, knee, and hip in 1001 community
      dwelling postmenopausal women aged 43-97 years (mean age 72). METHODS: OA at the
      hip, hand, and knee was defined by validated and standardized criteria based on
      pain history plus a clinical examination performed by a specially trained nurse.
      RESULTS: PME, validated by examination of pills and prescriptions, had been used
      for at least 1 year by 638 women (63.4%) for an average duration of 14.6 (+/
      10.6) years. OA prevalence was 34.5% among women who had used PME for at least 1
      year and 30.9% among women who did not use PME (age adjusted p = 0.02). Knee OA
      prevalence did not differ by PME use (p > 0.05). A significantly larger
      proportion of women who used PME for at least 1 year had hip and hand OA compared
      with women not using PME (4.1% vs. 1.1%, age-adjusted p = 0.002, and 15.8% vs.
      13.5%, age-adjusted p = 0.02, respectively). In analyses adjusted for the
      potential confounding effects of age, body mass index (BMI), smoking, exercise,
      and type of menopause, women who used PME still were more likely to have hip OA
      (odds ratio [OR] = 5.03, confidence interval [CI] = 1.70-14.84, p = 0.003) and
      hand OA ([OR] = 1.57, CI = 1.05-2.33, p = 0.03). Among estrogen users, duration
      of PME use was longer for women with OA than for women without OA (16 vs. 11
      median years, p = 0.01). CONCLUSIONS: PME is associated with a higher prevalence
      of clinical OA.

PMID- 12225626
TI  - Can obesity explain the racial difference in stage of breast cancer at diagnosis
      between black and white women?
AB  - OBJECTIVE: Black women are more likely to be diagnosed at a more advanced stage
      of breast cancer than are white women. Traditionally, this has been attributed in
      part to social or cultural factors. Given that black women are more likely to be
      obese than white women and that being obese is associated with a more advanced
      stage at diagnosis, this study aims to assess to what extent the racial
      difference in stage at diagnosis can be explained by racial differences in
      obesity. METHODS: Incident cases of breast cancer between 1991 and 1997 (white, n
      = 585; black, n = 381) were identified from hospitals in the Baltimore
      metropolitan area. Information, including age, race, weight, height, and
      pathology reports, was obtained from hospital medical records. RESULTS: Black
      women were more likely than white women to be diagnosed with breast cancer at
      tumor-node-metastasis (TNM) stage II or greater (age-adjusted odds ratio [OR] =
      1.51, 95% confidence interval [CI] 1.15-1.99). Further, black women were more
      likely than white women to be overweight or obese. A high body mass index (BMI)
      was significantly associated with an advanced stage of breast cancer at
      diagnosis. Adjustment for the higher prevalence of obesity in black women
      attenuated the risk estimate of more advanced stage of breast cancer at diagnosis
      in black women compared with white women by approximately 30%. CONCLUSIONS: Our
      results suggest that the higher prevalence of obesity among black women plays an
      important role in explaining their relative disadvantage in stage at diagnosis of
      breast cancer. Nonetheless, a racial difference in stage of breast cancer at
      diagnosis persists after adjustment for obesity.

PMID- 12225627
TI  - Breast cancer pathology practices among Medicare patients undergoing unilateral
      extended simple mastectomy.
AB  - OBJECTIVE: Information in pathology reports of breast cancer specimens is of
      critical importance to treating physicians for selection of local regional
      treatment and adjuvant therapy, evaluation of therapy, estimation of prognosis,
      and analysis of outcomes. This information is also of great importance to
      patients and their families. The Cancer Committee of the College of American
      Pathologists (CAP) and the Association of Directors of Anatomic and Surgical
      Pathology (ADASP) have published protocols for reporting the findings on breast
      cancer specimens to encourage adequate specimen examination and promote the
      reporting of findings in standardized formats and to provide treating physicians
      and their patients with vital information. METHODS: To assess the quality of
      breast cancer pathology practices and the degree to which they agree with
      published guidelines, we undertook a retrospective analysis among Medicare
      patients in New York State. Our random sample consisted of 748 (43.5%) of the
      1718 cases of unilateral extended simple mastectomy, also referred to as total
      mastectomy with lymph node dissection (ICD-9-CM procedure code 85.43), for
      calendar year 1999. Of these, 555 (74.2%) were available for study, whereas the
      rest did not satisfy inclusion criteria. Among the 555 cases, 545 (98.2%) were
      women, and 10 (1.8%) were men. The gender distribution was proportionately the
      same at 98.2% and 1.8% for all 1718 cases. RESULTS: We examined the 555 hospital
      records for 16 elements (quality indicators). Aggregate performance on 7 of these
      was > or =83.7%, and performance was < or = 69.4% on 9 others. There were
      significant interhospital disparities in performance levels for a number of
      quality indicators. Although some hospitals always recorded certain indicators,
      others never did. CONCLUSIONS: The issues with breast cancer pathology reports
      identified in this study are amenable to improvement to better serve patients,
      especially women, and their treating physicians in making adjuvant decisions,
      estimating prognosis, and evaluating outcomes.

PMID- 12225628
TI  - Behavior, heredity, and diabetes in college alumnae.
AB  - OBJECTIVE: Diabetes has been increasing in incidence and prevalence in the United
      States. Physical activity and exercise have been shown to lower the risk of
      noninsulin-dependent diabetes (NIDD), and family history and genetic factors are
      associated with both insulin-dependent diabetes (IDD) (type 1) and NIDD. The
      objective of this paper is to examine risk factors for diabetes in female college
      graduates as part of a study designed to determine the long-term health of former
      college athletes compared with nonathletes. The study was first conducted in 1981
      1982, and a follow-up study was conducted in 1996-1997. METHODS: The subjects for
      this paper are 3940 college alumnae (1945 former athletes and 1995 nonathletes),
      who participated in the follow-up study by responding to a self-administered
      questionnaire on medical history, health, family history, and behavioral
      practices. RESULTS: About 1.3% of the women reported physician-diagnosed
      diabetes, 0.9% of the former athletes, and 1.7% of the nonathletes. Former
      athletes had a significantly lower risk of NIDD, with an age-adjusted odds ratio
      (OR) of 0.41, 95% confidence level (CL) 0.2, 0.9. IDD was associated with a
      history of paternal diabetes (OR = 4.7, 95% CL 1.5, 14.9) and also with a history
      of diabetes in siblings (OR = 6.7, 95% CL 1.5, 30.1). NIDD was associated with a
      history of maternal diabetes (OR = 8.0, 95% CL 3.6, 17.8). Behavioral factors
      showed no association with IDD but were inversely associated with NIDD. The OR
      for being an athlete was 0.4, 95% CL 0.2, 0.9; for current regular exercise, OR =
      0.4, 95% CL 0.2, 0.9; low body mass index (BMI) compared to high BMI, OR = 0.2,
      95% CL 0.05, 0.60. CONCLUSIONS: The findings that IDD is associated with paternal
      diabetes and that NIDD may be maternally transmitted are not widely known,
      although the mode of transmission of diabetes is receiving increasing attention
      in the medical and genetic literature. This study confirms that modifiable
      behavioral practices, such as physical activity and weight control (i.e., optimal
      BMI), reduce the risk of NIDD.

PMID- 12225629
TI  - Preventive healthcare use, smoking, and alcohol use among Rhode Island women
      experiencing intimate partner violence.
AB  - OBJECTIVE: Intimate partner violence (IPV) poses major health threats to women,
      including increased risk for several chronic health conditions. The impact of IPV
      on use of preventive health services is not well understood. Although several
      studies indicate that female victims of IPV have higher rates of alcohol abuse,
      this has not been replicated in population-based studies. The association of IPV
      with smoking has not been a major research focus. The purpose of this study was
      to examine the association between physical and psychological IPV in the past 12
      months and preventive healthcare use, smoking, and alcohol use among women.
      METHODS: Data on 1643 women aged 18-54 from the 1999 Rhode Island Behavioral Risk
      Factor Surveillance System were analyzed. Logistic regression, controlling for
      age, race, marital status, education, insurance status, and functional
      disability, was used to model the associations of IPV with (1) checkups, (2)
      clinical breast examinations (CBEs), (3) Pap smear screening, (4) cigarette
      smoking, and (5) high-risk alcohol use. RESULTS: Prevalence of physical IPV was
      4.1%. The prevalence of psychological IPV, in the absence of physical IPV was
      4.5%. Physical IPV was associated with receiving regular Pap smears odds ratio
      ([OR] = 2.39, 95% confidence interval [CI] 1.01-5.70), current smoking (OR =
      2.07, 95% CI 1.03-4.18), and high-risk alcohol use (OR = 4.85, 95% CI 2.02
      11.60). Psychological IPV was associated with high-risk alcohol use (OR = 3.22,
      95% CI 1.46-7.09). CONCLUSIONS: Women experiencing IPV regularly access
      preventive healthcare, providing healthcare providers with opportunities to
      assess and counsel women for IPV in addition to smoking and high-risk alcohol
      use.

PMID- 12225632
TI  - Further evidence for a strong genetic influence on the development of autoimmune
      thyroid disease: the California twin study.
AB  - To determine the heritable component of Graves' disease (GD) more precisely, a
      disease survey questionnaire completed by 13,726 California-born twin pairs over
      the age of 37 years was used as the foundation of this study. On the basis of
      this survey, each member of pairs reporting a past diagnosis of GD was then
      sought for an extensive telephone interview to seek diagnostic confirmation.
      Successful diagnostic evaluation occurred in 108 cases, of which 99 affected twin
      pairs form the basis of this report. The results indicate that the estimated
      pairwise concordance for is 17% in monozygotic (MZ) twins, and 1.9% in dizygotic
      (DZ) twins, which are in close agreement with a recent report from a Danish twin
      population. Moreover, the reported 3.9% occurrence of GD found in the first
      degree relatives of affected twin pairs supports these findings. In contrast,
      only 0.45% of all twins, 0.27% of the spouses of twins, and approximately 0.16%
      of the first-degree relatives of unaffected twins were reported to have GD.
      Additionally, among the unaffected MZ twins of patients with GD, 17% reported
      having chronic thyroiditis and 10% other nonthyroid autoimmune conditions such as
      lupus erythematosus, pernicious anemia, or idiopathic thrombocytopenic purpura.
      Thus, a genetic predisposition appears to be shared for both thyroid and some
      nonthyroid autoimmune diseases. While it seems that GD is a strongly and
      nonspecifically heritable condition, the relatively low level of twin concordance
      indicates that this disease likely requires a nonheritable etiologic
      determinant(s) as well.

PMID- 12225634
TI  - Thyroid hormone gene targets in ROS 17/2.8 osteoblast-like cells identified by
      differential display analysis.
AB  - Thyroid hormone plays an important role in bone development and metabolism. We
      used a polymerase chain reaction (PCR)-based mRNA differential display (DD)
      analysis to obtain a profile of thyroid hormone-responsive genes in osteoblast
      like cells (ROS 17/2.8). ROS 17/2.8 cells were treated with 10(-8) M
      triiodothyronine (T(3)) for 2 and 24 hours. Total RNA was isolated, reverse
      transcribed, and amplified using a total of 72 combinations (2 hours) and 240
      combinations (24 hours) of 5' and 3' primers. At the 2-hour time point, 1 true
      positive novel clone was identified and shown to be the mitochondrial gene,
      subunit 6 of ATP synthase (ATPase-6). At the 24-hour time point, 3 differentially
      expressed (DE) mRNAs were confirmed as true-positives including; nonmuscle alkali
      myosin light chain (NM aMLC), ATPase-6, and one novel clone. T(3)-induction of
      ATPase-6 mRNA in ROS 17/2.8 cells was seen at 2 and 4 hours, but was maximal at
      24 hours (2.1-fold). T(3) induction of ATPase-6 mRNA was increased to fourfold in
      ROS 17/2.8 cells cultured at a low density. NM aMLC mRNA was modestly upregulated
      by T(3) in ROS 17/2.8 cells by 1.4-fold, and induction was augmented at low cell
      density to 1.7-fold. T(3) action on NM aMLC and on the mitochondrial gene ATPase
      6, represent novel targets and potential mediators of thyroid hormone action on
      bone. Cell type, and the extent of cell differentiation, influences T(3)
      regulation of genes in osteoblast-derived cells.

PMID- 12225633
TI  - Matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases and
      angiogenic cytokines in peripheral blood of patients with thyroid cancer.
AB  - Stimulation of growth of endothelial cells from preexisting blood vessels, i.e.,
      angiogenesis, is one of the essential elements necessary to create a permissive
      environment in which a tumor can grow. During angiogenesis, the matrix
      metalloproteinase (MMP) family of tissue enzymes contributes to normal
      (embriogenesis or wound repair) and pathologic tissue remodeling (chronic
      inflammation and tumor genesis). The proposed pathogenic roles of MMPs in cancer
      are tissue breakdown and remodeling during invasive tumor growth and tumor
      angiogenesis. Tissue inhibitors of metalloproteinases (TIMPs) form a complex with
      MMPs, which in turn inhibits active MMPs. Vascular endothelial growth factor
      (VEGF) and basic fibroblast growth factor (bFGF) are unique among mediators of
      angiogenesis with synergistic effect, and both can also be secreted by thyroid
      cancer cells. The goal of the study was to evaluate the plasma blood
      concentration of VEGF, bFGF, MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1, and TIMP
      2 in patients with cancer and in normal subjects. Twenty-two patients with
      thyroid cancers (papillary cancer, 11; partly papillary and partly follicular
      cancer, 3; anaplastic cancer, 5; medullary cancer, 3) and 16 healthy subjects
      (controls) were included in the study. VEGF, bFGF MMPs, and TIMPs were evaluated
      by enzyme-linked immunosorbent assay (ELISA). In patients with thyroid cancer,
      normal VEGF concentrations (74.29 +/- 13.38 vs. 84.85 +/- 21.71 pg/mL; p > 0.05)
      and increased bFGF (29.52 +/- 4.99 vs. 6.05 +/- 1.43 pg/mL; p < 0.001), MMP-2
      (605.95 +/- 81.83 vs. 148.75 +/- 43.53 ng/mL; p < 0.001), TIMP-2 (114.19 +/- 6.62
      vs. 60.75 +/- 9.18 ng/mL; p < 0.001), as well as lower MMP-1 (0.70 +/- 0.42 vs.
      3.87 +/- 0.53; p < 0.001) levels have been noted. Increased plasma levels of MMP
      3 and MMP-9 were also found in patients with medullary carcinoma. In conclusion,
      predominance of MMP-2 over TIMP-2 and TIMP-1 over MMP-1 as well as increased
      concentration of bFGF in peripheral blood are common features in patients with
      thyroid cancer.

PMID- 12225635
TI  - Cytotoxic T-lymphocyte antigen-4 gene polymorphisms and human T-cell
      lymphotrophic virus-1 infection: their associations with Hashimoto's thyroiditis
      in Japanese patients.
AB  - Cytotoxic T-lymphocyte antigen-4 (CTLA-4) decreases the immune response of T
      cells by inactivating the signal that occurs with interaction between CD28 on T
      cells and B7 on antigen-presenting cells. Gene polymorphisms involving CTLA-4
      promoter (-318 C/T), exon 1 (49 A/G), and exon 4 (microsatellite (AT)n) have been
      linked to Hashimoto's thyroiditis (HT) and other autoimmune diseases. HT also has
      a reported association with human T-cell lymphotrophic virus-1 (HTLV-1)
      infection. We investigated the occurrence of CTLA-4 polymorphisms in Japanese
      patients with HT with and without anti-HTLV-1 antibodies (HTLV-1 Ab). DNA samples
      from 143 patients with HT and 199 controls were subjected to polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) analysis using the
      restriction enzymes, Bbv 1, Tse 1, and Mse 1. In the HTLV-1 Ab-positive group the
      exon 1 G allele was more frequent in patients with HT than in controls (67% vs.
      53%, p = 0.0377), and in HTLV-1 Ab-negative group it was also frequent in
      patients with HT than in controls (68% vs. 53%, p = 0.0041). Frequency of the G
      allele in HT with HTLV-1 Ab was comparable to those without HTLV-1 Ab. Frequency
      of polymorphism in the promoter did not differ between patients with HT and
      controls, nor between controls with and without HTLV-1 Ab. HTLV-1 infection is
      not associated with CTLA-4 polymorphisms in either HT or controls. HTLV-1
      infection is not regulated by genetic factor such as CTLA-4, and may affect
      occurrence of HT as an independent purely environmental factor.

PMID- 12225636
TI  - Levels of soluble human leukocyte antigen class 1 are increased in Graves'
      disease and toxic multinodular goiter and correlate with the levels of
      triiodothyronine.
AB  - Soluble human leukocyte antigens class 1 (sHLA-1) are postulated to play a role
      in immunomodulation. Thyroid hormones and thyroid stimulating hormone influence
      expression of major histocompatibility complex (MHC) class 1 genes. We
      hypothesized similar changes in sHLA-1 with changes in the thyroid hormone. We
      measured serum levels of sHLA-1 in 140 normal controls, 11 patients with toxic
      multinodular goiter and 26 patients with active Graves' disease. On follow-up 1
      year after treatment for Graves' disease, we repeated the measurement of the
      levels of sHLA-1 in 21 patients. Levels of sHLA-1 were markedly elevated in the
      group of patients with active Graves' disease compared to the normal controls (p
      = 0.00016). The levels of sHLA-1 were also elevated significantly in patients
      with toxic multinodular goiter compared to normal controls (p = 0.034). There is
      no significant difference between genders and the two races tested among patients
      with Graves' disease in contrast to controls. Free triiodothyronine (T(3)) levels
      positively correlated with the levels of sHLA-1 (r = 0.61). On follow-up after
      treatment for Graves' disease, levels of sHLA-1 decreased by 62% with p = 0.0006
      (active Graves vs. follow-up). We conclude that there is a definite association
      between thyroid hormones and sHLA-1 levels.

PMID- 12225637
TI  - Current controversies in the management of pediatric patients with well
      differentiated nonmedullary thyroid cancer: a review.
AB  - Current treatment strategies for pediatric patients with nonmedullary, well
      differentiated thyroid carcinoma (WDTC) are derived from single-institution
      clinical cohorts, reports of extensive personal experience, and extrapolation of
      several common therapeutic practices for this tumor in adults. Because pediatric
      WDTC is an uncommon malignancy, the issues of its optimal initial and subsequent
      long-term treatment and follow-up remain controversial. Pediatric patients with
      WDTC can be divided into two groups: children younger than 10 years of age and
      teenagers/adolescents between 10 and 18 years of age because these groups have
      different recurrence and mortality rates. We hereby present our views and
      interpret them in the light of the pertinent literature. Our recommendations on
      treatment strategies are more relevant for younger children. After midpuberty,
      optimal treatment is adequately addressed in the relevant literature on adults.
      For the majority of patients, total/near-total thyroidectomy is currently
      recommended as the standard initial therapy for WDTC. This is commonly followed
      by administration of radioiodine (RAI; (131)I) therapy to destroy residual normal
      thyroid tissue (remnant). Routine (131)I remnant ablation has been shown to: (1).
      decrease the risk of local recurrences, (2) increase the sensitivity of
      subsequent diagnostic RAI whole-body scanning (WBS), and (3) render serum
      thyroglobulin (Tg) a highly sensitive marker for recurrent/residual disease
      during long-term follow-up. We recognize that the above practices are not
      universally adhered to in children and adolescents, because the risk
      stratification and intensity of applied therapeutic measures are influenced by
      institutional traditions and personal experience. In our view, aggressive initial
      management, followed by evaluations at regular intervals after thyroidectomy and
      (131)I remnant ablation, in conjunction with long-term thyroid hormone
      suppressive therapy (THST), result in decreased recurrence rates in pediatric
      patients with WDTC. Follow-up examinations should include a diagnostic RAI
      ((131)I or (123)I) WBS and measurement of serum Tg, both performed under
      conditions of TSH stimulation, as well as neck ultrasonography (US). Our strategy
      is corroborated by data from retrospective clinical cohort studies. In this
      malignancy, no evidence of disease (NED) status can be defined as the combination
      of a negative diagnostic WBS and the presence of undetectable or low serum Tg
      levels, both tested under TSH stimulation. These findings should be accompanied
      by the absence of anatomically definable disease by standard imaging modalities,
      e.g., neck US or chest computed tomography (CT). Although the long-term survival
      rates are good overall in this disease, selected patients may require further
      surgery or (131)I therapy for the eradication or clinical control of metastases.
      Finally, and importantly, because the duration of follow-up is lifelong, the care
      of children with prior diagnosis of WDTC should be transferred to an adult
      endocrinologist after they reach adulthood, even if they have achieved NED status
      by that time.

PMID- 12225638
TI  - Endoscopic thyroid surgery today: a diversity of surgical strategies.
AB  - The advancement of video-assisted minimally invasive surgery in this decade
      fostered the successful attempt at endoscopic thyroidectomy in 1997. This
      technically demanding surgery is now being evaluated in a small number of
      specialized centers. The procedure earned the most attention in Japan and is
      performed in more than 20 centers; a conference dedicated to the technique was
      held in Japan in 2001. By retrieving information from published or presented
      articles and direct personal communications, we report on the multitude of
      surgical strategies designed by different experts to enable relocalization of the
      surgical wounds to optimize cosmesis to the patient while complying with the gold
      standard of thyroid surgery.

PMID- 12225639
TI  - Relationship between tumor burden and serum thyroglobulin level in patients with
      papillary and follicular thyroid carcinoma.
AB  - Serum thyroglobulin (Tg) is a reliable marker for detecting recurrent and
      persistent disease during the follow-up of patients with papillary and follicular
      thyroid carcinoma. The goal of this study was to assess the relationship between
      the serum Tg level measured after thyroid hormone withdrawal and the tumor mass
      in thyroid cancer patients who underwent surgery with the use of an
      intraoperative probe for lymph node metastases with (131)I uptake. Patients were
      classified into one of three groups according to the Tg level: undetectable (n =
      18); 1-10 ng/mL (n = 21); and greater than 10 ng/mL (n = 33). The main clinical
      characteristics and the extent of the disease at the time of initial treatment
      were similar in these three groups. Lymph node metastases were found in 13 of the
      18 patients with undetectable Tg level. Eight patients had persistent foci of
      uptake after surgery that were located behind the sterno-clavicular joint in six
      patients. The number of metastatic lymph nodes and their total surface (in mm(2))
      or their total volume (in mm(3)) were significantly linked with serum
      Tg/thyrotropin [TSH] level (p = 0.002 and p < 0.0001, respectively). For a given
      metastatic surface or volume, the serum Tg/TSH value was no longer linked with
      the number of metastatic lymph nodes (p = 0.32), suggesting that the total
      surface or total volume is the characteristic that best summarizes the influence
      of the disease on the serum Tg/TSH level. In conclusion, patients with higher
      serum Tg levels tend to have more extensive disease and should undergo more
      aggressive treatment modalities. Nevertheless, undetectable serum Tg should not
      be considered as a reliable criteria to exclude a minimal tumor burden in
      patients who have already been treated with (131)I.

PMID- 12225640
TI  - Thyroid volume measurement in patients prior to radioiodine therapy: comparison
      between three-dimensional magnetic resonance imaging and ultrasonography.
AB  - Because of its cost effectiveness, wide availability, and technical ease of
      application, ultrasonography is the reference method for determining the thyroid
      volume prior to radioiodine therapy. The goal of the study is a prospective
      assessment of the deviation between volumetric ultrasonography measurements in
      comparison to those performed with three-dimensional magnetic resonance imaging
      (MRI). To that end, 60 consecutive patients with multinodular toxic goiter (n =
      28, 46.7%) or Graves' disease (n = 32, 53.3%) were included in the study.
      Ultrasonographic volumetry according to the well-known ellipsoid formula was
      performed by three different technicians. In addition, three-dimensional MRI
      scans of the neck area were acquired and evaluated by the ellipsoid formula as
      well as by a dedicated region-of-interest technique (MRI-ROI), which was used as
      standard of reference. While there was no significant difference between the
      ultrasonographic examinations of the three technicians, a highly significant mean
      deviation of 22.7% (10.4 mL) was found between the sonographic measurements and
      the MRI-ROI results (p < 0.01) that were underestimated in 80% of the cases.
      Correlation coefficients between the various volumetric approaches were highly
      significant, with values of at least 0.886 (p < 0.01). An additional analysis of
      volume-dependent subgroups revealed that thyroid volume had no significant
      influence on the results of ultrasonographic volumetry (p > 0.15). In conclusion,
      the study showed ultrasonography to be a reliable method of satisfactory accuracy
      that is appropriate for volumetric thyroid measurements. The findings indicate
      that the use of a correction factor higher than 0.52 in the ellipsoid formula is
      recommended to improve accuracy. However, further studies are necessary to
      confirm these findings.

PMID- 12225641
TI  - Influence of iodine intake on the diagnostic power of fine-needle aspiration
      cytology of the thyroid gland.
AB  - In order to determine whether the iodine intake influences the diagnostic power
      of ultrasound-guided fine-needle aspiration cytology (US-FNAC), patients with
      nontoxic nodular goiter from an area with sufficient iodine intake (IS) (n = 938,
      median iodine excretion [MIE] = 103 microg/L) and from an iodine-deficient (ID)
      area (n = 3,601, MIE = 75 microg/L) were investigated. Elevated rates of
      multinodularity (59.6% vs. 49.6%, p < 0.001), nonpalpable nodules (47.6% vs.
      37.3%, p < 0.001) and nondiagnostic US-FNACs (8.8% vs. 5.1%, p = 0.008), and a
      lower malignancy rate (1.2% vs. 2.3%, p = 0.006) were found in the ID area.
      Follicular tumors were encountered among positive findings. Cytohistologic
      comparison (ID, n = 416; IS, n = 97) revealed that the sensitivity, specificity,
      and diagnostic accuracy of US-FNAC were similar in the two areas (95.5% vs.
      92.3%, 78.3% vs. 71.1%, 82.4% vs. 80.6%, IS vs. ID area, respectively), while a
      lower malignancy rate and a higher ratio of benign to malignant tumors were
      observed in the ID than in the IS area (10.1% vs. 22.6%, p < 0.001, and 4.38 vs.
      1.50, p < 0.001, respectively). This resulted in a lower positive predictive
      value of US-FNAC in the ID (36/106) than in the IS area (21/36, p = 0.001),
      because the rate of false US-FNAC was higher in benign (67/184) than in malignant
      tumors (4/61, p < 0.001).

PMID- 12225642
TI  - Thyroid ultrasound versus antithyroid peroxidase antibody determination: a cohort
      study of four hundred fifty-one subjects.
AB  - Autoimmune thyroiditis is mirrored by a hypoechoic ultrasound pattern. We
      determined diagnostic precision of thyroid sonography compared to that of anti
      thyroid peroxidase antibody (TPOAb) concentration. Ambulatory patients with
      unknown thyroid status (n = 451; 407 female, ages 44 +/- 16 years; 45 male, ages
      50 +/- 14 years) excluding those with suspected hyperthyroidism or on drugs known
      to cause hypothyroidism were recruited consecutively. Subjects were recruited
      from a specialized thyroid outpatient unit with higher frequencies of thyroid
      disorders than in the general population. Before determination of thyroid
      function and TPOAb concentration thyroid volume (normal values: women < 12 mL,
      men < 14 mL) and echogenicity (grade 1 = normal: similar to submandibular gland,
      hyperechoic to neck muscles; grade 2: hypoechoic to submandibular gland,
      hyperechoic to neck muscles, grade 3: iso-/hypoechoic to neck muscles) were
      determined. Positive predictive value of grade 3 pattern for detection of
      autoimmune thyroiditis was 94% (with overt hypothyroidism) and 96% (with any
      degree of hypothyroidism), that of grade 2 or 3 85% and 87%, respectively.
      Negative predictive value of grade 1 pattern for detection of euthyroid TPOAb
      negative subjects was 91%. Goiter was present in 31% and 21% of TPOAb postive and
      negative subjects, respectively, while 11% and 15% had an atrophic thyroid gland
      (p = not significant [n.s.]). Given a high intraobserver and interobserver
      agreement abnormal thyroid ultrasound patterns were highly indicative of
      autoimmune thyroiditis and allowed the detection of thyroid dysfunction with 96%
      probability.

PMID- 12225643
TI  - Homocysteine: a risk factor for cardiovascular disease in subclinical
      hypothyroidism?
AB  - The role of homocysteine as a causal risk factor for cardiovascular disease
      remains controversial. Moderately elevated total plasma homocysteine levels have
      been reported in patients with overt hypothyroidism, a condition that is
      associated with an increased risk for cardiovascular disease. Recently,
      subclinical hypothyroidism has been identified as an independent risk factor for
      atherosclerosis and myocardial infarction in elderly women. Therefore, we
      measured prospectively total fasting plasma homocysteine levels in 37 consecutive
      subjects (6 males, 31 females, mean age 50 +/- 18 standard deviation [SD] years)
      with newly diagnosed subclinical hypothyroidism at baseline and after 3-4 months
      of levothyroxine supplementation. During levothyroxine treatment concentrations
      of thyrotropin (TSH) decreased from 10.1 +/- 5.8 (SD) to 1.5 +/- 1.8 mU/L.
      Fasting total plasma homocysteine levels were not elevated at baseline (9.9 +/-
      2.9 micromol/L) and remained unchanged (9.6 +/- 3.5 micromol/L) after
      levothyroxine treatment. Serum folate or vitamin B(12) levels also remained
      unchanged. We conclude that subclinical hypothyroidism is not associated with
      hyperhomocysteinemia. Levothyroxine supplementation has no influence on total
      plasma homocysteine levels in subclinical hypothyroidism. Hence, total plasma
      homocysteine does not appear to contribute to the increased risk for
      atherosclerotic disease and myocardial infarction in patients with subclinical
      hypothyroidism.

PMID- 12225644
TI  - Graves' ophthalmopathy associated with interferon-alpha treatment for hepatitis
      C.

PMID- 12225646
TI  - Perchlorate: low dose exposure and susceptible populations.

PMID- 12225647
TI  - To treat or not to treat? The unusual story of two unmarried sisters with goiter.

PMID- 12225648
TI  - Hyper or hypo?

PMID- 12225649
TI  - Memories from an interview.

PMID- 12225651
TI  - Partial return of motor function in paralyzed legs after surgical bypass of the
      lesion site by nerve autografts three years after spinal cord injury.
AB  - Spinal cord injuries often result in irreversible loss of motor and somatosensory
      functions below the lesion level. Treatment is limited to physiotherapy aimed at
      compensating disability. We previously showed that re-establishment of tissue
      continuity can be achieved in animal models through nerve autografts implanted
      between the rostral spinal ventral horn and the caudal ventral roots. Rostral
      motor neuron axons could thus reach peripheral targets, leading to some return of
      motor function. We used a similar approach in a paraplegic patient with
      stabilized clinical states three years after spinal cord traumatic damage at the
      T9 level. Three segments from autologous sural nerves were implanted into the
      right and left antero-lateral quadrant of the cord at T7-8 levels, then connected
      to homolateral L2-4 lumbar ventral roots, respectively. Eight months after
      surgery, voluntary contractions of bilateral adductors and of the left quadriceps
      were observed. Muscular activity was confirmed by motor unit potentials in
      response to attempted muscle contraction. Motor-evoked potentials from these
      muscles were recorded by transcranial magnetic stimulation. These data support
      the hypothesis that muscles have been re-connected to supra-spinal centers
      through motor neurons located in the rostral stump of the damaged cord. They
      suggest that delayed surgical reconstruction of motor pathways may contribute to
      partial functional recovery.

PMID- 12225652
TI  - NBQX treatment improves mitochondrial function and reduces oxidative events after
      spinal cord injury.
AB  - The purpose of this study was to examine the effects of inhibiting ionotropic
      glutamate receptor subtypes on measures of oxidative stress events at acute times
      following traumatic spinal cord injury (SCI). Rats received a moderate contusion
      injury and 15 min later were treated with one of two doses of 1,2,3,4-tetrahydro
      6-nitro-2,3-dioxo-benzol[f]quinoxaline-7-sulfonamide disodium (NBQX), MK-801, or
      the appropriate vehicle. At 4 h following injury, spinal cords were removed and a
      crude synaptosomal preparation obtained to examine mitochondrial function using
      the MTT assay, as well as measures of reactive oxygen species (ROS), lipid
      peroxidation, and glutamate and glucose uptake. We report here that intraspinal
      treatment with either 15 or 30 nmol of NBQX improves mitochondrial function and
      reduces the levels of ROS and lipid peroxidation products. In contrast, MK-801,
      given intravenously at doses of 1.0 or 5.0 mg/kg, was without effect on these
      same measures. Neither drug treatment had an effect on glutamate or glucose
      uptake, both of which are reduced at acute times following SCI. Previous studies
      have documented that drugs acting on non-N-methyl-D-aspartate (NMDA) receptors
      exhibit greater efficacy compared to NMDA receptor antagonists on recovery of
      function and tissue sparing following traumatic spinal cord injury. The results
      of this study provide a potential mechanism by which blockade of the non-NMDA
      ionotropic receptors exhibit positive effects following traumatic SCI.

PMID- 12225653
TI  - Association between cerebrospinal fluid interleukin-6 concentrations and outcome
      after severe human traumatic brain injury.
AB  - Acute inflammation plays a significant role in the pathophysiology of traumatic
      brain injury (TBI). However, the specific relationships between inflammatory
      mediators and patient outcome following TBI have not been fully established. In
      this study, we measured plasma and cerebrospinal fluid interleukin-1 (IL-1) and
      interleukin-6 (IL-6) concentrations in 36 patients, following severe TBI.
      Patients were monitored with continuous measurements of somatosensory-evoked
      potentials (SSEP) to derive an established surrogate outcome measurement, the 96
      h evoked potential (SSEP96). Clinical outcomes were assessed at 3 months using
      the Glasgow Outcome Scale (GOS). Peak cerebrospinal fluid (CSF) IL-1 and IL-6
      concentrations were significantly higher than those observed in the plasma
      [median 6.5 pg/mL (range 1.4-25.0) vs. 3.0 (0.8-7.6) for IL-1, and 650 (130
      7,214) vs. 253 (52-1,506) for IL-6, p < 0.001 for both]. Peak CSF IL-6 levels
      correlated with SSEP96 (r = 0.42; p = 0.0133), and peak CSF IL-6 levels were
      higher with improved GOS (p = 0.024). Multiple regression analysis identified
      that age (p = 0.0072), pupillary abnormality (p = 0.021), the presence of mass
      lesion (p = 0.023), and peak CSF IL-6 concentrations (p = 0.026) were all
      statistically significant predictors of clinical outcome following TBI. These
      results suggest that peak CSF IL-6 concentrations correlate with improved outcome
      following TBI. This finding helps to characterize the inflammatory reaction
      associated with TBI and may help to develop improved treatment strategies for
      patients with TBI.

PMID- 12225654
TI  - Improved recovery and delayed cytokine induction after closed head injury in mice
      with central overexpression of the secreted isoform of the interleukin-1 receptor
      antagonist.
AB  - The acute inflammatory response following traumatic brain injury (TBI) has been
      shown to play an important role in the development of secondary tissue damage.
      The proinflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor
      alpha (TNFalpha), are induced early after brain injury and have been implicated
      in the delayed damage. The IL-1 receptor antagonist (IL-1ra) has been shown to
      modulate the proinflammatory cytokine cascade by blocking the binding of IL-1 to
      its signaling receptor. In this study, we investigated the effect of transgenic
      overexpression of IL-1ra on the cytokine expression and neurological damage in a
      closed head injury (CHI) model of TBI. The neurological recovery, as analyzed by
      neurological severity score (NSS), was significantly higher in transgenic mice
      overexpressing the human secreted form of IL-1ra in astrocytes, directed by the
      murine glial fibrillary acidic protein promoter, as compared to wild-type mice.
      Analysis of tissue levels of cytokines by ELISA showed increased levels of
      TNFalpha in the cerebral cortex from the wild type mice 1 h after injury. After 4
      h significant increases in the levels of IL-1beta and IL-6 were observed in the
      wild type mice. In the transgenic mice, on the other hand, no effect on TNFalpha
      levels was observed and no significant increases in IL-1beta and IL-6 levels
      could be detected until 6 h after injury. Thus, it can be concluded that blockage
      of IL-1 signaling by elevated levels of IL-1ra has a neuroprotective effect, in
      agreement with previous reports, and that central overexpression of IL-1ra
      results in delayed proinflammatory cytokine induction and improved neurological
      recovery after traumatic brain injury.

PMID- 12225655
TI  - LF 16-0687 Ms, a bradykinin B2 receptor antagonist, reduces brain edema and
      improves long-term neurological function recovery after closed head trauma in
      rats.
AB  - Bradykinin is an endogenous inflammatory agent that enhances vascular
      permeability and produces tissue edema. We investigated whether LF 16-0687 Ms, a
      potent nonpeptide antagonist of bradykinin type-2 (B(2)) receptor, was able to
      reduce brain swelling and to improve the recovery of neurological function
      following closed head trauma (CHT) in rats. In dose-effect studies, LF 16-0687 Ms
      doses of 0.75-4.5 mg/kg given 1 h after trauma significantly reduced the
      development of edema in the injured hemisphere by a maximum of 70%. It had no
      effect on the brain water content of sham-operated rats. LF 16-0687 Ms also
      significantly improved neurological recovery evaluated by a Neurological Severity
      Score (NSS) based on motor, reflex, and behavioral tests. In time-window studies
      LF 16-0687 Ms (2.25 mg/kg) was given 1, 2, 4, and 10 h after CHT. The extent of
      edema was significantly reduced when LF 16-0687 Ms was given 1 h (-45%), 2 h (
      52%), and 4 h (-63%) but not 10 h (-24%) after CHT. Given at any time-point, LF
      16-0687 Ms significantly improved the recovery of the NSS at 24 h. In duration of
      treatment studies, rats tended to recover normal neurological function over 14
      days after CHT. However, time to recovery was longer in severely than in
      moderately injured animals, unless they were treated with LF 16-0687 Ms. This
      study provides further evidence that blockade of bradykinin B(2) receptors
      represents a potential effective approach to the treatment of focal cerebral
      contusions.

PMID- 12225656
TI  - Relationship between NOC/oFQ, dynorphin, and COX-2 activation in impaired NMDA
      cerebrovasodilation after brain injury.
AB  - Previous studies have observed that the recently described endogenous opioid,
      nociceptin/orphanin FQ (NOC/oFQ), contributes to impairment of N-methyl-D
      aspartate (NMDA)-induced cerebrovasodilation following fluid percussion brain
      injury (FPI) via a cyclooxygenase (COX)-dependent generation of superoxide anion
      (O(2)(-)). This study was designed to investigate the relationship between
      NOC/oFQ, another opioid, dynorphin, and activation of the COX-2 isoform of the
      enzyme in such impaired dilation to NMDA after FPI in piglets equipped with a
      closed cranial window. Superoxide dismutase (SOD)-inhibitable nitroblue
      tetrazolium (NBT) reduction was determined as an index of O(-)(2) generation.
      Under non-brain injury conditions, NOC/oFQ (10(-10) M), the CSF concentration
      observed after FPI, increased CSF dynorphin, while the NOC/oFQ antagonist [F/G]
      NOC/oFQ (1-13) NH(2) attenuated the stimulated release of dynorphin following FPI
      (34 +/- 3 and 97 +/- 6 vs. 36 +/- 3 and 68 +/- 8 pg/mol for CSF dynorphin before
      and after FPI in untreated and NOC/oFQ antagonist-pretreated animals). FPI
      increased SOD-inhibitable NBT reduction, but pretreatment with
      norbinaltorphimine, a dynorphin antagonist, or NS398, a COX-2 inhibitor, blunted
      such reduction (1 +/- 1 vs. 19 +/- 3 vs. 4 +/- 1 vs. 4 +/- 1 pmol/mm(2) for
      control, FPI, FPI-norbinaltorphimine and FPI-NS398, respectively). Under non
      brain injury conditions, dynorphin, in a concentration observed in CSF after FPI,
      also increased SOD-inhibitable NBT reduction, which was blunted by NS398. NMDA
      induced pial artery dilation was reversed to vasoconstriction following FPI, but
      pretreatment with norbinaltorphimine or NS398 partially protected such responses
      (9 +/- 1 and 16 +/- 1, control; - 8 +/- 1 and - 13 +/- 2, FPI; 6 +/- 1 and 12 +/-
      1% FPI-norbinaltorphimine for NMDA 10(-8), 10(-6) M, respectively). These data
      show that NOC/oFQ modulates the CSF release of dynorphin after FPI. These data
      also show that dynorphin contributes to O(2)(-) generation after FPI via COX-2
      activation. These data additionally indicate that dynorphin and COX-2 activation
      contribute to impairment of NMDA pial artery dilation after FPI. Finally, these
      data suggest that NOC/oFQ impairs NMDA dilation postinsult via the sequential
      release of dynorphin, activation of COX-2, and generation of O(2)(-).

PMID- 12225657
TI  - BetaIII tubulin-expressing neurons reveal enhanced neurogenesis in hippocampal
      and cortical structures after a contusion trauma in rats.
AB  - Neurogenesis is not only restricted to embryonic development, but also occurs in
      adult mammalian brains, including human. In this study, evidence is provided,
      that neurogenesis is involved in the repair of hippocampal and cortical
      structures after CNS injury. Cortical contusion was induced in 8-week-old Wistar
      rats. This trauma resulted in a primary cortical lesion and ipsilateral distant
      remote hippocampal damage, involving primarily CA3-pyramidal cells. The
      progression of injury was followed over a time course of 7 days, using Nissl
      staining and a monoclonal antibody against betaIII tubulin-a specific marker for
      neurogenic cells. Nissl staining showed a partial recovery of damaged cortical
      and hippocampal cells at day 7. This recovery was accompanied by an increase of
      neurogenic cells in these structures, particularly in the dentate gyrus and the
      neocortical areas. Taken together, these findings provide evidence for the
      involvement of neurogenesis in the repair processes after traumatic brain injury.

PMID- 12225658
TI  - Exposure to short-lasting impulse noise causes neuronal c-Jun expression and
      induction of apoptosis in the adult rat brain.
AB  - Exposure to impulse noise, above a certain intensity, is harmful to auditory
      function. Effects of impulse noise on the central nervous system (CNS) are
      largely unexplored, and there is little information on critical threshold values
      and time factors. We have recently shown that neurofilament proteins are affected
      in the cerebral cortex and the hippocampus. Now we show that impulse noise
      induces expression of the immediate early gene c-Jun products, proposed to play a
      role in the initiation of neuronal death, and apoptosis as revealed by TUNEL
      staining. Rat brains were investigated immunohistochemically 2 h to 21 days after
      exposure to impulse noise of 198 dB or 202 dB. c-Jun was expressed in neuronal
      perikarya in layers II-VI of the temporal cortex, the cingulate and the piriform
      cortices at 2 h to 21 days after both exposure levels. Granule neurons of the
      dentate gyrus and the CA1-3 in the hippocampus pyramidal neurons were similarly
      affected. The elevated expression of c-Jun products remained high at all
      postexposure times. TUNEL staining was positive among the same nerve cell
      populations 6 h after exposure and persisted even at 7 days at both exposure
      levels.

PMID- 12225659
TI  - Single burr hole evacuation for traumatic acute subdural hematoma of the
      posterior fossa in the emergency room.
AB  - A 57-year-old man and a 55-year-old man presented with acute subdural hematoma of
      the posterior cranial fossa due to trauma. Both were comatose preoperatively.
      Emergent single burr hole evacuation in the posterior cranial fossa was performed
      in the emergency room immediately after computed tomography. Neurological
      symptoms improved dramatically just after initiating the burr hole evacuation in
      both patients. A 57-year-old man became alert and could walk unassisted 1 month
      after surgery. The other could walk with assistance 4 months after surgery,
      although psychic disturbance resulting from cerebral contusion remained. Single
      burr hole evacuation in the emergency room is a useful treatment for acute
      subdural hematoma of the posterior cranial fossa because the procedure can be
      performed easily and rapidly, thus achieving reduction of intracranial pressure.
      Progressing neurological deterioration, reversibility of brainstem function by
      mannitol administration and the sign of brainstem compression and
      noncommunicating hydrocephalus are good indicators for this treatment.

PMID- 12225660
TI  - TOR deficiency in C. elegans causes developmental arrest and intestinal atrophy
      by inhibition of mRNA translation.
AB  - BACKGROUND: TOR is a phosphatidylinositol kinase (PIK)-related kinase that
      controls cell growth and proliferation in response to nutritional cues. We
      describe a C. elegans TOR homolog (CeTOR) and phenotypes associated with CeTOR
      deficiency. These phenotypes are compared with the response to starvation and the
      inactivation of a variety of putative TOR targets. RESULTS: Whether caused by
      mutation or RNA interference, TOR deficiency results in developmental arrest at
      mid-to-late L3, which is accompanied by marked gonadal degeneration and a
      pronounced intestinal cell phenotype. A population of refractile, autofluorescent
      intestinal vesicles, which take up the lysosomal dye Neutral Red, increases
      dramatically in size, while the number of normal intestinal vesicles and the
      intestinal cytoplasmic volume decrease progressively. This is accompanied by an
      increase in the gut lumen size and a compromise in the intestine's ability to
      digest and absorb nutrients. CeTOR-deficient larvae exhibit no significant dauer
      characteristics, but share some features with starved L3 larvae. Notably,
      however, starved larvae do not have severe intestinal atrophy. Inactivation of C.
      elegans p70S6K or TAP42 homologs does not reproduce CeTOR deficiency phenotypes,
      nor does inactivation of C. elegans TIP41, a putative negative regulator of CeTOR
      function, rescue CeTOR deficiency. In contrast, inactivating the C. elegans eIF
      4G homolog and eIF-2 subunits results in developmental arrest accompanied by the
      appearance of large, refractile intestinal vesicles and severe intestinal atrophy
      resembling that of CeTOR deficiency. CONCLUSIONS: The developmental arrest and
      intestinal phenotypes of CeTOR deficiency are due to an inhibition of global mRNA
      translation. Thus, TOR is a major upstream regulator of overall mRNA translation
      in C. elegans, as in yeast.

PMID- 12225661
TI  - De-etiolated 1 and damaged DNA binding protein 1 interact to regulate Arabidopsis
      photomorphogenesis.
AB  - BACKGROUND: Plant development is exquisitely sensitive to light. Seedlings grown
      in the dark have a developmentally arrested etiolated phenotype, whereas in the
      light they develop leaves and complete their life cycle. Arabidopsis de-etiolated
      1 (det1) mutants develop like light-grown seedlings even when grown in the dark.
      DET1 encodes a nuclear protein that appears to act downstream from multiple
      photoreceptors to regulate morphogenesis and gene expression in response to
      light. However, its function has remained unknown. RESULTS: We used microarrays
      to examine defects in transcription in dark-grown det1 seedlings. We found
      extensive changes in gene expression, including many of the transcriptional
      responses observed in light-treated wild-type seedlings. We used an epitope
      tagging approach to determine the basis of DET1 function. GFP-DET1 rescues the
      det1 phenotype, is localized to the nucleus, and forms an approximately 350 kDa
      complex, which is required for full DET1 activity. We affinity-purified the DET1
      complex and identified an approximately 120 kDa copurifying protein that is the
      plant homolog of UV-Damaged DNA Binding Protein 1 (DDB1), a protein implicated in
      the human disease xeroderma pigmentosa. A null mutation in Arabidopsis DDB1A
      results in no obvious phenotype on its own, yet it enhances the phenotype of a
      weak det1 allele. CONCLUSIONS: DET1 and DDB1 interact both biochemically and
      genetically. In animal cells, DDB1 interacts with histone acetyltransferase
      complexes. The DET1/DDB1 complex may regulate gene expression in response to
      light via recruitment of HAT activity. Thus, DET1, whose sequence is conserved in
      both animals and plants, may play a direct role in the regulation of many genes.

PMID- 12225662
TI  - The dynamics of homologous chromosome pairing during male Drosophila meiosis.
AB  - BACKGROUND: Meiotic pairing is essential for the proper orientation of
      chromosomes at the metaphase plate and their subsequent disjunction during
      anaphase I. In male Drosophila melanogaster, meiosis occurs in the absence of
      recombination or a recognizable synaptonemal complex (SC). Due to limitations in
      available cytological techniques, the early stages of homologous chromosome
      pairing in male Drosophila have not been observed, and the mechanisms involved
      are poorly understood. RESULTS: Chromosome tagging with GFP-Lac repressor protein
      allowed us to track, for the first time, the behavior of meiotic chromosomes at
      high resolution, live, at all stages of male Drosophila meiosis. Homologous
      chromosomes pair throughout the euchromatic regions in spermatogonia and during
      the early phases of spermatocyte development. Extensive separation of homologs
      and sister chromatids along the chromosome arms occurs in mid-G2, several hours
      before the first meiotic division, and before the G2/M transition. Centromeres,
      on the other hand, show complex association patterns, with specific homolog
      pairing taking place in mid-G2. These changes in chromosome pairing parallel
      changes in large-scale chromosome organization. CONCLUSIONS: Our results suggest
      that widespread interactions along the euchromatin are required for the
      initiation, but not the maintenance, of meiotic pairing of autosomes in male
      Drosophila. We propose that heterochromatic associations, or chromatid
      entanglement, may be responsible for the maintenance of homolog association
      during late G2. Our data also suggest that the formation of chromosome
      territories in the spermatocyte nucleus may play an active role in ensuring the
      specificity of meiotic pairing in late prophase by disrupting interactions
      between nonhomologous chromosomes.

PMID- 12225664
TI  - Rapid movement of microtubules in axons.
AB  - Cytoskeletal and cytosolic proteins are transported along axons in the slow
      components of axonal transport at average rates of about 0.002-0.1 microm/s. This
      movement is essential for axonal growth and survival, yet the mechanism is poorly
      understood. Many studies on slow axonal transport have focused on tubulin, the
      subunit protein of microtubules, but attempts to observe the movement of this
      protein in cultured nerve cells have been largely unsuccessful. Here, we report
      direct observations of the movement of microtubules in cultured nerve cells using
      a modified fluorescence photobleaching strategy combined with difference imaging.
      The movements are rapid, with average rates of 1 microm/s, but they are also
      infrequent and highly asynchronous. These observations indicate that microtubules
      are propelled along axons by fast motors. We propose that the overall rate of
      movement is slow because the microtubules spend only a small proportion of their
      time moving. The rapid, infrequent, and highly asynchronous nature of the
      movement may explain why the axonal transport of tubulin has eluded detection in
      so many other studies.

PMID- 12225665
TI  - A novel function for the Sm proteins in germ granule localization during C.
      elegans embryogenesis.
AB  - General mRNA processing factors are traditionally thought to function only in the
      control of global gene expression. Here we show that the Sm proteins, core
      components of the splicesome, also regulate germ granules during early C. elegans
      development. Germ granules are large cytoplasmic particles that localize to germ
      cells and their precursors during embryogenesis of diverse organisms. In C.
      elegans, germ granules, called P granules, are segregated to the germline
      precursor cells during embryogenesis by asymmetric cell division, and they remain
      in germ cells at all stages of development. We found that at least some Sm
      proteins are components of P granules. Moreover, disruption of Sm activity caused
      defects in P granule localization to the germ cell precursors during early
      embryogenesis. In contrast, loss of other splicing factor activities had no
      effect on germ granule control in the embryo. These observations suggest that the
      Sm proteins control germ granule integrity and localization in the early C.
      elegans embryo and that this role is independent of pre-mRNA splicing. Thus, a
      highly conserved splicing factor may have been adapted to control both snRNP
      biogenesis and the localization of components important for germ cell function.

PMID- 12225663
TI  - CARPEL FACTORY, a Dicer homolog, and HEN1, a novel protein, act in microRNA
      metabolism in Arabidopsis thaliana.
AB  - BACKGROUND: In metazoans, microRNAs, or miRNAs, constitute a growing family of
      small regulatory RNAs that are usually 19-25 nucleotides in length. They are
      processed from longer precursor RNAs that fold into stem-loop structures by the
      ribonuclease Dicer and are thought to regulate gene expression by base pairing
      with RNAs of protein-coding genes. In Arabidopsis thaliana, mutations in CARPEL
      FACTORY (CAF), a Dicer homolog, and those in a novel gene, HEN1, result in
      similar, multifaceted developmental defects, suggesting a similar function of the
      two genes, possibly in miRNA metabolism. RESULTS: To investigate the potential
      functions of CAF and HEN1 in miRNA metabolism, we aimed to isolate miRNAs from
      Arabidopsis and examine their accumulation during plant development in wild-type
      plants and in hen1-1 and caf-1 mutant plants. We have isolated 11 miRNAs, some of
      which have potential homologs in tobacco, rice, and maize. The putative
      precursors of these miRNAs have the capacity to form stable stem-loop structures.
      The accumulation of these miRNAs appears to be spatially or temporally controlled
      in plant development, and their abundance is greatly reduced in caf-1 and hen1-1
      mutants. HEN1 homologs are found in bacterial, fungal, and metazoan genomes.
      CONCLUSIONS: miRNAs are present in both plant and animal kingdoms. An
      evolutionarily conserved mechanism involving a protein, known as Dicer in animals
      and CAF in Arabidopsis, operates in miRNA metabolism. HEN1 is a new player in
      miRNA accumulation in Arabidopsis, and HEN1 homologs in metazoans may have a
      similar function. The developmental defects associated with caf-1 and hen1-1
      mutations and the patterns of miRNA accumulation suggest that miRNAs play
      fundamental roles in plant development.

PMID- 12225666
TI  - Conservation of intramembrane proteolytic activity and substrate specificity in
      prokaryotic and eukaryotic rhomboids.
AB  - Rhomboid is an intramembrane serine protease responsible for the proteolytic
      activation of Drosophila epidermal growth factor receptor (EGFR) ligands.
      Although nothing is known about the function of the approximately 100 currently
      known rhomboid genes conserved throughout evolution, a recent analysis suggests
      that a Rhomboid from the pathogenic bacterium Providencia stuartii is involved in
      the production of a quorum-sensing factor. This suggests that an intercellular
      signaling mechanism may have been conserved between prokaryotes and metazoans.
      However, the function of prokaryotic Rhomboids is unknown. We have examined the
      ability of eight prokaryotic Rhomboids to cleave the three Drosophila EGFR
      ligands. Despite their striking sequence divergence, Rhomboids from one Gram
      positive and four Gram-negative species, including Providencia, specifically
      cleaved Drosophila substrates, but not similar proteins such as Transforming
      Growth Factor alpha (TGFalpha) and Delta. Although the sequence similarity
      between these divergent Rhomboids is very limited, all contain the putative
      serine catalytic triad residues, and their specific mutation abolished protease
      activity. Therefore, despite low overall homology, the Rhomboids are a family of
      ancient, functionally conserved intramembrane serine proteases, some of which
      also have conserved substrate specificity. Moreover, a function for Rhomboids in
      activating intercellular signaling appears to have evolved early.

PMID- 12225667
TI  - Targeting of Nir2 to lipid droplets is regulated by a specific threonine residue
      within its PI-transfer domain.
AB  - Nir2, like its Drosophila homolog retinal degeneration B (RdgB), contains an N
      terminal phosphatidylinositol-transfer protein (PI-TP)-like domain. Previous
      studies have suggested that RdgB plays an important role in the fly
      phototransduction cascade and that its PI-transfer domain is critical for this
      function. In this domain, a specific mutation, T59E, induces a dominant retinal
      degeneration phenotype. Here we show that a similar mutation, T59E in the human
      Nir2 protein, targets Nir2 to spherical cytosolic structures identified as lipid
      droplets by the lipophilic dye Nile red. A truncated Nir2T59E mutant consisting
      of only the PI-transfer domain was also targeted to lipid droplets, whereas
      neither the wild-type Nir2 nor the Nir2T59A mutant was associated with lipid
      droplets under regular growth conditions. However, oleic-acid treatment caused
      translocation of wild-type Nir2, but not translocation of the T59A mutant, to
      lipid droplets. This treatment also induced partial targeting of endogenous Nir2,
      which is mainly associated with the Golgi apparatus, to lipid droplets. Targeting
      of Nir2 to lipid droplets was attributed to its enhanced threonine
      phosphorylation. These results suggest that a specific threonine within the PI
      transfer domain of Nir2 provides a regulatory site for targeting to lipid
      droplets. In conjunction with the role of PI-TPs in lipid transport, this
      targeting may affect intracellular lipid trafficking and distribution and may
      provide the molecular basis underlying the dominant effect of the RdgB-T59E
      mutant on retinal degeneration.

PMID- 12225668
TI  - Functional analysis of the tubulin-folding cofactor C in Arabidopsis thaliana.
AB  - The biogenesis of microtubules comprises several steps, including the correct
      folding of alpha- and beta-tubulin and heterodimer formation. In vitro studies
      and the genetic analysis in yeast revealed that, after translation, alpha- and
      beta-tubulin are processed by several chaperonins and microtubule-folding
      cofactors (TFCs) to produce assembly-competent alpha-/beta-tubulin heterodimers.
      One of the TFCs, TFC-C, does not exist in yeast, and a potential function of TFC
      C is thus based only on the biochemical analysis. In this study and in a very
      recently published study by Steinborn and coworkers, the analysis of the
      Arabidopsis porcino (por) mutant has shown that TFC-C is important for
      microtubule function in vivo. The predicted POR protein shares weak amino acid
      similarity with the human TFC-C (hTFC-C). Our finding that hTFC-C under the
      control of the ubiquitously expressed 35S promoter can rescue the por mutant
      phenotype shows that the POR gene encodes the Arabidopsis ortholog of hTFC-C. The
      analysis of plants carrying a GFP:POR fusion construct showed that POR protein is
      localized in the cytoplasm and is not associated with microtubules. While, in por
      mutants, microtubule density was indistinguishable from wild-type, their
      organization was affected.

PMID- 12225669
TI  - The fusome and microtubules enrich Par-1 in the oocyte, where it effects
      polarization in conjunction with Par-3, BicD, Egl, and dynein.
AB  - After its specification, the Drosophila oocyte undergoes a critical polarization
      event that involves a reorganization of the microtubules (MT) and relocalization
      of the determinant Orb within the oocyte. This polarization requires Par-1 kinase
      and the PDZ-containing Par-3 homolog, Bazooka (Baz). Par-1 has been observed on
      the fusome, which degenerates before the onset of oocyte polarization. How Par-1
      acts to polarize the oocyte has been unclear. Here we show that Par-1 becomes
      restricted to the oocyte in a MT-dependent fashion after disappearance of the
      fusome. At the time of polarization, the kinase itself and the determinant
      BicaudalD (BicD) are relocalized from the anterior to the posterior of the
      oocyte. Par-1 and BicD are interdependent and require MT and the minus end
      directed motor Dynein for their relocalization. We show that baz is required for
      Par-1 relocalization within the oocyte and that the distributions of Baz and Par
      1 in the Drosophila oocyte are complementary and strikingly reminiscent of the
      two PAR proteins in the C. elegans embryo. We propose that, through the combined
      actions of the fusome, MT, and Baz, Par-1 is selectively enriched and localized
      within the oocyte, where, in conjunction with BicD, Egalitarian (Egl), and
      Dynein, it acts on the MT cytoskeleton to effect polarization.

PMID- 12225670
TI  - The photomorphogenesis regulator DET1 binds the amino-terminal tail of histone
      H2B in a nucleosome context.
AB  - Light provides a major source of information from the environment during plant
      growth and development. Recent results suggest that the key events controlling
      light-regulated gene expression in plants are translocation of the phytochrome
      photoreceptors into the nucleus, followed by their binding to transcription
      factors such as PIF3. Coupled with this, the degradation of positively acting
      intermediates such as the transcription factor HY5 by COP1 and the COP9
      signalosome appears to be an important process whereby photomorphogenesis is
      repressed in darkness (e.g., ). Genetic analyses in Arabidopsis and tomato have
      revealed that the nuclear protein DET1 also plays a key role in the repression of
      photomorphogenesis. However, the function of this protein has remained a mystery.
      In a series of in vitro experiments, we provide persuasive evidence that DET1
      binds to nonacetylated amino-terminal tails of the core histone H2B in the
      context of the nucleosome. Furthermore, we have utilized FRET (fluorescence
      resonance energy transfer) imaging with GFP variants to demonstrate this
      interaction within the nucleus of living plant cells. Given the dramatic
      photomorphogenic phenotypes of det1 mutants, we propose that chromatin remodeling
      plays a heretofore unsuspected role in regulating gene expression during
      photomorphogenesis.

PMID- 12225671
TI  - PPW-1, a PAZ/PIWI protein required for efficient germline RNAi, is defective in a
      natural isolate of C. elegans.
AB  - One of the remarkable aspects about RNA interference (RNAi) in Caenorhabditis
      elegans is that the trigger molecules, dsRNA, can be administered via the
      animal's food. We assayed whether this feature is a universal property of the
      species by testing numerous strains that have been isolated from different parts
      of the globe. We found that one isolate from Hawaii had a defect in RNAi that was
      specific to the germline and was a result of multiple mutations in a PAZ/PIWI
      domain-containing protein, which we named PPW-1. Deleting ppw-1 in the canonical
      C. elegans strain Bristol N2 makes it resistant to feeding of dsRNA directed
      against germline-expressed genes. PPW-1 belongs to the Argonaute family of
      proteins, which act in posttranscriptional gene silencing and development, and is
      homologous to the RNAi gene rde-1. Our data indicate that at least two members of
      this family are required for complete and effective RNAi in C. elegans.

PMID- 12225673
TI  - New thinking on gene patents.
AB  - With the number of patent claims including DNA sequence booming, is there a way
      forward to help resolve disagreements over the many issues involved? One ethical
      body believes that there is and has produced a new study.

PMID- 12225672
TI  - Posterior localization of dynein and dorsal-ventral axis formation depend on
      kinesin in Drosophila oocytes.
AB  - To establish the major body axes, late Drosophila oocytes localize determinants
      to discrete cortical positions: bicoid mRNA to the anterior cortex, oskar mRNA to
      the posterior cortex, and gurken mRNA to the margin of the anterior cortex
      adjacent to the oocyte nucleus (the "anterodorsal corner"). These localizations
      depend on microtubules that are thought to be organized such that plus end
      directed motors can move cargoes, like oskar, away from the anterior/lateral
      surfaces and hence toward the posterior pole. Likewise, minus end-directed motors
      may move cargoes toward anterior destinations. Contradicting this, cytoplasmic
      dynein, a minus-end motor, accumulates at the posterior. Here, we report that
      disruption of the plus-end motor kinesin I causes a shift of dynein from
      posterior to anterior. This provides an explanation for the dynein paradox,
      suggesting that dynein is moved as a cargo toward the posterior pole by kinesin
      generated forces. However, other results present a new transport polarity puzzle.
      Disruption of kinesin I causes partial defects in anterior positioning of the
      nucleus and severe defects in anterodorsal localization of gurken mRNA. Kinesin
      may generate anterodorsal forces directly, despite the apparent preponderance of
      minus ends at the anterior cortex. Alternatively, kinesin I may facilitate
      cytoplasmic dynein-based anterodorsal forces by repositioning dynein toward
      microtubule plus ends.

PMID- 12225675
TI  - Chronostasis.

PMID- 12225674
TI  - Welsh I am.
AB  - With developments in genetics, researchers are increasingly able to address
      historical issues surrounding human migration and provenance by studying present
      populations. Nigel Williams reports on one of the latest studies looking at a
      crucial period of British history.

PMID- 12225676
TI  - Lethal moves.

PMID- 12225677
TI  - Visual neurophysiology: recordings from the human primate.
AB  - Neurophysiological studies in human patients, with experiments of the kind
      traditionally reserved for monkeys, are beginning to provide valuable insight
      into the workings of the brain. Taking center stage is the question of which
      neurons lie at the heart of perception itself.

PMID- 12225678
TI  - Cell division: MAST sails through mitosis.
AB  - Successful mitosis requires coordinated activities of microtubules and numerous
      associated proteins. A recent study implicates the microtubule-associated protein
      MAST/Orbit in a surprisingly wide array of mitotic activities, ranging from
      maintaining mitotic spindle bipolarity to tethering chromosomes to the ends of
      microtubules.

PMID- 12225679
TI  - Algal rhodopsins: phototaxis receptors found at last.
AB  - The discovery of two distinct Chlamydomonas sensory receptors responsible for
      phototaxis reveals additional diversity among the microbial rhodopsins. Sequence
      and architecture comparisons among this growing family highlight key components
      for light-responsive functions.

PMID- 12225680
TI  - Visual system: 'S' is not for saccades.
AB  - Coloured flashes that are visible only to the short-wavelength-sensitive S cones
      interfere with shifts of visual attention but not with shifts of gaze (saccades).
      Attention and gaze must therefore be directed by different visual sub-systems.

PMID- 12225681
TI  - Actin nucleation: cortactin caught in the act.
AB  - A variety of activators stimulate Arp2/3 complex to nucleate branched actin
      filament structures. New results provide important biochemical and structural
      information for activation by the proteins cortactin and N-WASP.

PMID- 12225682
TI  - Intermediate filaments: vimentin moves in.
AB  - Vimentin intermediate filaments move bi-directionally along microtubules in the
      cell. Recent work has identified the microtubule motor cytoplasmic dynein as the
      missing inward-directed motor that drives this movement.

PMID- 12225683
TI  - Visual attention: light enters the jungle.
AB  - Recent studies focusing on basic visual attributes, such as luminance, colour and
      motion, are providing a starting point for investigating the relationship between
      perceptual and neural manifestations of attention.

PMID- 12225684
TI  - Vertebrate sex determination: a new player in the field.
AB  - Sex-determining genes have been identified in flies, worms and mammals but not,
      until recently, in non-mammalian vertebrates. Now, a gene has been isolated from
      the Y chromosome of the teleost fish medaka that is functionally comparable to
      the mammalian testis-determining gene, Sry.

PMID- 12225686
TI  - Toward a systematic approach to understanding--and ultimately eliminating-
      African American women's health disparities.

PMID- 12225687
TI  - Race, ethnicity, and disparities in breast cancer: victories and challenges.

PMID- 12225688
TI  - Racial and ethnic disparities in coronary heart disease in women: prevention,
      treatment, and needed interventions.

PMID- 12225689
TI  - Public health addresses racial and ethnic disparities in coronary heart disease
      in women: perspectives from the Centers for Disease Control and Prevention.

PMID- 12225690
TI  - Enhancing the technology of clinical trials and the trials model to evaluate
      newly developed, targeted antidepressants.
AB  - Concern about disappointing results from recent multi-center trials of new
      antidepressants prompted several ACNP workshops on "improving the technology of
      clinical trials." The workshops focused on technical problems, such as patient
      screening, reliability of clinical ratings, and the role of the placebo control.
      They aimed to determine how to more effectively apply the current clinical trials
      model for evaluating antidepressant drugs. The problems confronting the field of
      clinical trials, however, extend beyond technology. They also included conceptual
      issues concerning changes in the understanding of depressive disorders and of the
      multiple actions of antidepressant drugs. Such problems have been further
      complicated by the rapidly changing field of drug development itself, which is
      continually refining the targeting of new antidepressant agents. Drugs are
      increasingly being developed to try to change specific behavioral facets more
      rapidly and may be less likely, therefore, to act initially on "whole" disorders.
      To address such issues, a symposium was held in Rhodes in 2000 that focused on
      such conceptual changes with the goal of developing recommendations to revise the
      clinical evaluation model. Its purpose was to integrate new knowledge on
      depression and the mechanisms of action of antidepressant drugs toward developing
      more efficient methods of drug development. Since the evaluation process will
      eventually require changes in governmental policy, senior staff from the National
      Institute of Mental Health (NIMH) , Unites States and Food and Drug
      Administration (FDA), Unites States participated as well as members of academia,
      industry and clinical practice. Recommendations for altering clinical trial
      methodology were made in four areas: patient selection, methodology of
      evaluation, measuring onset of action, and FDA and NIMH perspectives on current
      practice. This article discusses these four areas and presents the consensus of
      the panel participants.

PMID- 12225691
TI  - Neurokinins activate local glutamatergic inputs to serotonergic neurons of the
      dorsal raphe nucleus.
AB  - It has been proposed that antidepressant effects of neurokinin NK(1) receptor
      blockade may result from an increase in serotonin (5-HT) transmission. However,
      the mechanism by which neurokinins influence 5-HT neurons is not known. In this
      study, local NK(1) and NK(3) receptor-mediated responses in 5-HT neurons of the
      dorsal raphe nucleus (DRN) were studied using intracellular recording in rat
      brain slices. Bath application of the NK(1) receptor agonist substance P (SP) or
      the NK(3) receptor agonists senktide and NKB induced a robust increase in
      "spontaneous" excitatory postsynaptic currents (EPSCs) in 5-HT neurons. The EPSCs
      were blocked by the AMPA/kainate glutamate receptor antagonist CNQX and the fast
      Na(+) channel blocker tetrodotoxin (TTX), indicating that the increase in EPSCs
      resulted from an increase in impulse flow in local glutamatergic neuronal
      afferents. The neurokinins agonists had no direct excitatory effects on 5-HT
      neurons and no NK(1) or NK(3) receptor immunolabeling was found in 5-HT-labeled
      neurones. However, neurokinins, by increasing excitatory postsynaptic potentials
      (EPSPs), did increase the spiking of 5-HT neurons. The SP- and NKB-induced EPSCs
      were preferentially blocked by NK(1) and NK(3) antagonists, and there was minimal
      cross-desensitization between agonists at the two receptors. We conclude that
      neurokinins, via distinct NK(1) and NK(3) receptors, could promote 5-HT
      transmission, at least in part, by exciting a local population of glutamatergic
      inputs to 5-HT neurons in the DRN. However, these local excitatory effects,
      viewed within the context of the global effects of neurokinins on 5-HT neurons,
      reveal important differences between the functional role of NK(1) and NK(3)
      receptors.

PMID- 12225692
TI  - Galanin is a potent in vivo modulator of mesencephalic serotonergic
      neurotransmission.
AB  - Neurochemical, molecular, immunohistochemical and behavioral methods were used to
      examine the in vivo effects of the neuropeptide galanin on central 5-HT
      neurotransmission and on 5-HT(1A) receptor-mediated responses. Intraventricularly
      infused galanin caused a long-lasting and dose-dependent reduction of basal
      extracellular 5-HT levels in the ventral hippocampus of awake rats as measured by
      microdialysis. Infusion of galanin into the dorsal raphe nucleus (DRN), but not
      intra-hippocampally, reduced 5-HT release. The effect of i.c.v. galanin on 5-HT
      release was blocked by the galanin receptor antagonist M35, acting most likely
      via galanin receptors at the level of the DRN. Galanin also reduced the levels of
      tryptophanhydroxylase mRNA in the DRN. Therefore, the effects of galanin on 5
      HT(1A) receptor-mediated responses were further investigated. Surprisingly,
      galanin significantly attenuated the reduction of hippocampal 5-HT release
      induced by systemic injection of the 5-HT(1A) receptor agonist 8-OH-DPAT. Galanin
      also attenuated 8-OH-DPAT-induced hypothermia and locomotor activity in rats.
      These results indicate that galanin has important inhibitory actions on central 5
      HT neurotransmission and on 5-HT(1A) receptor-mediated events.

PMID- 12225693
TI  - The gerbil elevated plus-maze I: behavioral characterization and pharmacological
      validation.
AB  - Several neurokinin NK1 receptor antagonists currently being developed for anxiety
      and depression have reduced affinity for the rat and mouse NK1 receptor compared
      with human. Consequently, it has proven difficult to test these agents in
      traditional rat and mouse models of anxiety and depression. This issue has been
      overcome, in part, by using non-traditional lab species such as the guinea pig
      and gerbil, which have NK1 receptors closer in homology to human NK1 receptors.
      However, there are very few reports describing the behavior of gerbils in
      traditional models of anxiety. The aim of the present study was to determine if
      the elevated plus-maze, a commonly used anxiety model, could be adapted for the
      gerbil. Using a specially-designed elevated plus-maze, gerbils exhibited an
      'anxious' behavioral profile similar to that observed in rats and mice, i.e.,
      reduced entries into, and time spent exploring, an open, aversive arm. The
      anxiolytic drugs diazepam (0.03-3 mg/kg i.p.), chlordiazepoxide (0.3-10 mg/kg
      i.p.), and buspirone (0.3-30 mg/kg s.c.) increased open arm exploration and
      produced anxiolytic-like effects on risk-assessment behaviors (reduced stretch
      attend postures and increased head dips). Of particular interest, the
      antidepressant drugs imipramine (1-30 mg/kg p.o.), fluoxetine (1-30 mg/kg, p.o.)
      and paroxetine (0.3-10 mg/kg p.o.) each produced some acute anxiolytic-like
      activity, without affecting locomotor activity. The antipsychotic, haloperidol,
      and the psychostimulant, amphetamine, did not produce any anxiolytic-like effects
      (1-10 mg/kg s.c). The anxiogenic beta-carboline, FG-7142, reduced time spent in
      the open arm and head dips, and increased stretch-attend postures (1-30 mg/kg,
      i.p.). These studies have demonstrated that gerbils exhibit an anxiety-like
      profile on an elevated plus-maze, and that the gerbil elevated plus-maze may have
      predictive validity for anxiolytics, and antidepressants with potential
      anxiolytic-like effects.

PMID- 12225694
TI  - The gerbil elevated plus-maze II: anxiolytic-like effects of selective neurokinin
      NK1 receptor antagonists.
AB  - Neurokinin NK1 receptor antagonists may have therapeutic potential in the
      treatment of anxiety and depression. Species variants in the NK1 receptor result
      in reduced affinity of NK1 receptor antagonists at rat and mouse NK1 receptors,
      making it difficult to test NK1 antagonists in traditional preclinical models of
      anxiety and depression. Gerbil NK1 receptors are similar in homology to the human
      NK1 receptor. In a companion article, we described the anxiety-like behavioral
      profile of gerbils on an adapted elevated plus-maze, and the ability of
      anxiolytic drugs to produce anti-anxiety effects in the gerbil elevated plus
      maze. The aim of the present study was to determine whether oral (p.o.)
      administration of the NK1 receptor antagonists MK-869, L-742,694, L-733,060, CP
      99,994, and CP-122,721 produced anxiolytic-like effects in the gerbil elevated
      plus-maze. Upon testing, all five NK1 antagonists produced anxiolytic-like
      effects. MK-869 (0.01-3 mg/kg) was the most potent NK1 antagonist, producing
      anxiolytic-like effects on percentage of open arm time, percentage of open arm
      entries, stretch-attend postures, and head dips at 0.03-0.3 mg/kg doses. L
      742,694 (1-30 mg/kg) and L-733,060 (1-10 mg/kg) produced anxiolytic-like effects
      on percentage of open arm time and stretch-attend postures at 3-10 mg/kg doses.
      CP-99,994 (3-30 mg/kg) only produced an anxiolytic-like effect on stretch-attend
      postures. CP-122,721 (3-30 mg/kg) produced an anxiolytic-like effect on
      percentage of open arm time at 30 mg/kg. The order of potency of the NK1
      antagonists to increase percentage of open arm time was very similar to their
      potency to block NK1 agonist-induced foot-tapping. These studies demonstrate that
      neurokinin NK1 receptor antagonists produce anxiolytic-like effects in a novel
      gerbil elevated plus-maze, and suggest that this is an appropriate model to test
      NK1 antagonists for preclinical anxiolytic activity.

PMID- 12225695
TI  - Autonomic changes associated with enhanced anxiety in 5-HT(1A) receptor knockout
      mice.
AB  - 5-HT(1A) receptor knockout (KO) mice have been described as more anxious in
      various anxiety paradigms. Because anxiety is often associated with autonomic
      changes like elevated body temperature and tachycardia, radiotelemetry was used
      to study these parameters in wild type (WT) and KO mice in stress-/anxiety
      related paradigms. Basal body temperature (BT), heart rate (HR), and their
      diurnal rhythmicity did not differ between well-adapted WT and KO mice. In a
      simple stress-test, the Stress-induced Hyperthermia (SIH), injection-stress
      resulted in an exaggerated stress-response in KO mice. Furthermore, the 5-HT(1A)
      receptor agonist flesinoxan dose-dependently antagonized SIH and stress-induced
      tachycardia in WT, but not in KO, mice. In both genotypes, diazepam blocked SIH,
      but not stress-induced tachycardia. Finally, KO mice displayed an exaggerated
      stress response in HR and BT to novelty stress; this was supported by behavioral
      indications of enhanced anxiety. The present findings show that 5-HT(1A) receptor
      KO mice display a more "anxious-like" phenotype not only at a behavioral, but
      also at autonomic levels.

PMID- 12225696
TI  - Effect of selective blockade of mu(1) or delta opioid receptors on reinstatement
      of alcohol-seeking behavior by drug-associated stimuli in rats.
AB  - This study examined the effects of a nonselective opiate antagonist and
      antagonists selective for the mu(1) versus delta opioid receptor on ethanol
      seeking behavior induced by alcohol-related environmental stimuli in an animal
      model of relapse. Rats were trained to self-administer ethanol (10% w/v) or water
      on an FR 1 schedule in 30-min daily sessions. The availability of ethanol was
      signaled by an olfactory discriminative stimulus (S(+)). A different olfactory
      stimulus (S(-)) signaled water availability. In addition, each lever-response
      resulting in delivery of ethanol was paired with illumination of a visual cue for
      5 s (SC(+)), whereas a 5-s white noise (SC(-)) was associated with water. The
      rats were then subjected to a 20-day extinction phase where lever presses had no
      programmed consequences. Reexposure to the S(+)/CS(+) stimulus condition in the
      absence of further ethanol availability elicited strong recovery of responding.
      No effect was observed following presentation of S(-)/CS(-). Subsequently,
      ethanol-seeking behavior associated with the S(+)/CS(+) stimulus condition was
      studied in rats treated with the nonselective opiate antagonist naltrexone (0.25
      1 mg/kg, SC), the delta selective antagonist naltrindole (1-5 mg/kg, IP), and the
      mu(1) selective antagonist naloxonazine (1-15 mg/kg, IP). Naltrexone (1 mg/kg)
      and naltrindole (5 mg/kg) selectively inhibited alcohol-seeking behavior.
      Naloxonazine (15 mg/kg) also reduced ethanol-seeking behavior but produced some
      nonselective behavioral suppression as well. The results provide evidence that
      selective blockade of either mu(1) or delta opioid receptors inhibits ethanol
      seeking behavior elicited by drug-related environmental stimuli. Moreover, the
      data suggest that drugs aimed at the delta opioid receptor may offer advantages
      in the treatment and prevention of relapse compared with agents that also block
      the mu(1) receptor.

PMID- 12225697
TI  - Comparisons of behavioral and neurochemical characteristics between WKY, WKHA,
      and Wistar rat strains.
AB  - WKHA rats constitute a recombinant inbred rat strain derived by phenotypic
      selection of the progeny of hybrid F2 crosses between SHR and WKY rats. WKHA are
      normotensive and show some features of hyperactivity and of hyper-reactivity to
      stress, but their utility as model of attention deficit/hyperactivity disorder
      (ADHD) has not yet been settled. To address these questions, we performed
      behavioral and neurochemical evaluations of WKHA, and compared them to both WKY
      and Wistar (WIS) rats. In locomotor activity tests, the respective scores for
      each strain were WKY<WKHA<WIS. The relative amplitudes of the inhibition of the
      startle response by preexposure of the animals to a low-level acoustic cue
      (prepulse inhibition (PPI) stimulus filtering test) were WKY< WKHA = WIS. In
      nontreated rats, prepulse inhibition was significantly lower in WKY than in WIS
      and WKHA rats at low prepulse intensity. Methylphenidate did not decrease
      locomotor activity in any of the strains, but rather increased locomotion, with
      the effect being of higher amplitude in WKY. Methylphenidate also impaired
      prepulse inhibition in a dose-dependent manner. In situ hybridization for NGFI-B,
      a transcription factor related to the dopaminergic system, revealed that
      methylphenidate increased the expression of NGFI-B mRNA in the accumbens
      (core/shell) and striatum only in WKY rats. We conclude that: (1) the behavioral
      differences between WKY and WKHA can be more readily explained by deficits
      present in WKY than by unusual characteristics of WKHA, (2) the WKHA does not
      appear to represent a useful model of ADHD, and (3) the use of WKY rats as the
      only control for behavioral studies is potentially misleading, because they show
      a combination of behavioral and neurochemical (dopamine-related) characteristics
      that make them very different from other common rat strains. Although these
      characteristics may make them interesting models in their own right, it also
      follows that the conclusions of any study based on comparisons of one particular
      strain to just WKY should be interpreted very cautiously.

PMID- 12225698
TI  - Effects of long-term acetyl-L-carnitine administration in rats: I. increased
      dopamine output in mesocorticolimbic areas and protection toward acute stress
      exposure.
AB  - Acetyl-L-carnitine (ALCAR) is the acetyl ester of carnitine that has been
      reported to be beneficial in depressive disorders and Alzheimer's disease. A 7
      day administration of ALCAR in rats increased dopamine and serotonin output in
      the nucleus accumbens shell and it prevented the development of escape deficit
      produced by acute exposure to unavoidable stress. No tolerance developed to this
      protective effect, which appeared to be mediated by (1) the activation of 5
      HT(1A) receptors, as it was antagonized by the administration of WAY100635 30 min
      before stress exposure; and (2) a process of neuronal plasticity dependent on
      NMDA receptor activity, as subcutaneous dizocilpine infusion during ALCAR
      treatment prevented the development of the protective effect on stress. Chronic
      stress exposure maintains an escape deficit condition that is reverted by a long
      term treatment with antidepressants, but the same condition was not modified by
      long-term ALCAR administration. Thus, ALCAR cannot be defined as an
      antidepressant.

PMID- 12225699
TI  - Selective serotonin reuptake inhibitors decrease impulsive behavior as measured
      by an adjusting delay procedure in the pigeon.
AB  - The inability to delay gratification (reinforcement or reward) is one index of
      impulsive behavior. In order to measure the willingness of pigeons to delay
      reinforcement, an adjustable delay schedule was developed that allowed daily
      approximations of an indifference point between immediate brief access to
      reinforcer and delayed, longer access to reinforcer. Acute administration of the
      anxiolytic alprazolam (5 mg/kg) decreased the length of delay tolerated before a
      larger reinforcement. Likewise, acute administration of the anxiolytic
      chlordiazepoxide (10 mg/kg) produced a similar, although not significant, effect.
      Neither acute nor five daily injections of 8-OH-DPAT, a 5-HT(1A) agonist, or
      WAY100635, a 5-HT(1A) antagonist, affected the length of the delay period.
      Chronic (17 day), but not acute injections of the selective serotonin reuptake
      inhibitors (SSRIs) fluoxetine (10 mg/kg), citalopram (10 mg/kg) and paroxetine (3
      mg/kg) increased the delay period. When given in addition to 1 mg/kg of 8-OH
      DPAT, but not 1 mg/kg WAY100635, the effect of fluoxetine was accelerated in that
      the increase in delay was observed earlier in the treatment. These data support
      the use of SSRIs to decrease impulsive behavior. Addition of a 5-HT(1A) agonist,
      but not a 5-HT(1A) antagonist, to the SSRI may hasten the therapeutic activity of
      the SSRI in treating impulsivity.

PMID- 12225700
TI  - SR46349-B, a 5-HT(2A/2C) receptor antagonist, potentiates haloperidol-induced
      dopamine release in rat medial prefrontal cortex and nucleus accumbens.
AB  - The combination of M100907, a putative antipsychotic drug (APD) and serotonin (5
      HT)(2A) antagonist, and the typical APD haloperidol, can enhance dopamine (DA)
      release in rat medial prefrontal cortex (mPFC), an effect which has been
      postulated to be of value to improve cognition and negative symptoms. The present
      study demonstrated that another putative APD and 5-HT(2A/2C) antagonist, SR46349
      B (10 mg/kg, but not 1-3 mg/kg) alone, but not M100907 (0.1 and 3 mg/kg) alone,
      increased mPFC DA release, whereas neither drug alone affected nucleus accumbens
      (NAC) DA release. Neither SR46349-B nor M100907 alone affected nucleus accumbens
      (NAC) DA release. Neither SR46349-B nor M100907 alone affected nucleus accumbens
      (NAC) DA release. SR46349-B (3 mg/kg) potentiated haloperidol-induced DA release
      in both regions, whereas M100907 (0.1 mg/kg) potentiated haloperidol (0.1 mg/kg)
      induced mPFC DA release and inhibited it in the NAC. WAY100635 (0.2 mg/kg), a 5
      HT(1A) antagonist, abolished the effects of haloperidol plus M100907 as well as
      SR46349-B on DA release in the mPFC, but did not do so in the NAC. Thus, 5-HT(2A)
      and 5-HT(2A/2C) antagonism together with haloperidol-induced D(2) antagonism may
      potentiate mPFC DA release via 5-HT(1A) agonism, whereas the combined effects of
      these agents on NAC DA release is not dependent upon 5-HT(1A) receptor
      stimulation. Interestingly, similar to the effect of SR46349-B, high dose M100907
      (3 mg/kg), which might have antagonist activity at 5-HT(2C) receptors,
      potentiated 1 mg/kg haloperidol-induced DA release in the mPFC and NAC. These
      results suggest that 5-HT(2A/2C) antagonism may be more advantageous than
      selective 5-HT(2A) antagonism as an adjunct to D(2) antagonists to improve
      cognition and negative symptoms in schizophrenia.

PMID- 12225701
TI  - Response of the hypothalamic-pituitary-adrenal axis to stress in the absence and
      presence of ethanol in subjects at high and low risk of alcoholism.
AB  - Both genetic and environmental factors, such as stress, are important in
      determining alcohol consumption. Furthermore, both stress and alcohol influence
      the activity of the hypothalamic-pituitary-adrenal (HPA)-axis. Thus, the present
      studies investigated the response of the HPA axis to stress and the effect of
      ethanol on the stress response, in subjects at high (HR) and low (LR) risk of
      alcoholism as determined from their family history. Twenty HR and 20 LR subjects
      performed a stress-inducing task 30 min following the ingestion of either a
      placebo drink or a low dose of ethanol. The levels of plasma adrenal
      corticotropic hormone (ACTH) and cortisol were measured prior to and for four
      hours following initiation of the treatment. Changes with time in the plasma
      hormone levels following ingestion of either a placebo or an ethanol drink,
      without the performance of the stress task, served as controls to compare the
      stress-induced changes. Neither the placebo nor the ethanol drink altered the
      plasma ACTH and cortisol concentrations. High risk subjects presented lower basal
      ACTH, but not cortisol, levels and a lower stress-induced increase in plasma ACTH
      concentration than LR subjects. Furthermore, the HR subjects presented a delayed
      post-stress recovery of the plasma ACTH and cortisol levels. Ethanol consumption
      prior to the stress task attenuated (ACTH) or abolished (cortisol) the stress
      induced increase in the plasma hormone concentrations of both LR and HR subjects.
      Thus, there are quantitative differences on the response of the HPA-axis to
      stress between HR and LR subjects, while ingestion of low amounts of ethanol
      prior to the performance of the stress task had a similar effect on HR and LR
      individuals.

PMID- 12225702
TI  - Metabolite alterations in basal ganglia associated with methamphetamine-related
      psychiatric symptoms. A proton MRS study.
AB  - Following the chronic use of methamphetamine, some individuals experience
      psychosis and anxiety. One reason may be the persistence of metabolite
      abnormalities in the brain of currently abstinent former methamphetamine users.
      In this study, N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr+PCr),
      and choline-containing compound (Cho) levels were measured in the left and right
      basal ganglia using proton magnetic resonance spectroscopy (MRS) in 13 abstinent
      methamphetamine users and 11 healthy comparison subjects with no history of
      illicit drug use. The methamphetamine users showed a significantly reduced
      Cr+PCr/Cho ratio in the bilateral basal ganglia compared with the healthy
      comparison subjects. Furthermore, the reduction in the Cr+PCr/Cho ratio was
      significantly correlated with the duration of methamphetamine use and with the
      severity of residual psychiatric symptoms. NAA/Cho ratios in the bilateral basal
      ganglia did not significantly differ between methamphetamine users and comparison
      subjects. These findings suggest that protracted use of methamphetamine may cause
      metabolite alterations in the basal ganglia. Furthermore, residual psychiatric
      symptoms may be attributable to the metabolite alterations in the basal ganglia.

PMID- 12225703
TI  - Different effects of phenelzine treatment on EEG topography in waking and sleep
      in depressed patients.
AB  - A novel approach to investigate the relationship between depression and changes
      in sleep-wake regulatory mechanisms used the monoamine oxidase inhibitor (MAOI)
      phenelzine that is known to suppress rapid-eye-movement (REM) sleep. Sleep
      architecture and EEG topography during wakefulness and sleep were studied in
      eight depressed patients before and after five weeks of treatment with phenelzine
      (30-90 mg/day), which induced a significant alleviation of depressive symptoms.
      Theta power (4.75-7.5 Hz) during a 5-min wake EEG prior to sleep increased two
      fold during administration of phenelzine. REM sleep was almost completely
      eliminated. This latter effect was compensated by increased duration of stage 2,
      whereas total sleep time was not shortened. In non-REM sleep (stages 2, 3, and
      4), treatment slightly reduced EEG power between 2.0-6.25 Hz and 8.5-13.75 Hz;
      power in the 16.75-25.0 Hz band increased. Activity in the delta band (2.0-3.25
      Hz) tended to be reduced in the fronto-central derivation, but not in centro
      parietal and parieto-occipital derivations. However, the Treatment X Derivation
      interaction was not significant. These data indicate that in contrast to
      wakefulness the effects of phenelzine treatment on the EEG in non-REM sleep were
      small. Rank correlation analyses revealed no association between the
      antidepressant treatment response and the changes in sleep and EEG power spectra
      during administration of phenelzine.

PMID- 12225704
TI  - Lithium augmentation increases the ACTH and cortisol response in the combined
      DEX/CRH test in unipolar major depression.
AB  - Lithium augmentation is a well established strategy for treatment-resistant
      depression. The exact mode of its action is unknown, but an enhancement of
      serotonergic transmission is hypothesized. The authors investigated changes in
      the hypothalamic-pituitary-adrenocortical (HPA) system during lithium
      augmentation and their correlation to clinical response by means of the combined
      dexamethasone/CRH test (DEX/CRH test). Thirty patients with unipolar major
      depressive episodes (DSM IV) who had not responded to an adequate trial with an
      antidepressant were assessed on the day before lithium augmentation (baseline)
      with the DEX/CRH test (pretreatment with 1.5 mg dexamethasone p.o. at 11 P.M. and
      CRH stimulation at 3 P.M. on the next day). Twenty-four patients were re-assessed
      after response was determined or, in cases of non-response, four weeks after
      initiation of lithium augmentation. Response to lithium augmentation was measured
      by weekly ratings on the Hamilton Depression Rating Scale (HDRS 17-item version).
      Response was defined as a DeltaHDRS of > or =50% and an endpoint score of < 10.
      Patients had a significantly higher ACTH and cortisol response to CRH stimulation
      during lithium augmentation compared with the values at baseline. There was no
      difference in ACTH and cortisol reaction between responders and non-responders to
      lithium augmentation. This increase is in contrast to the known normalization of
      HPA-axis overdrive after treatment with a tricyclic antidepressant like
      amitriptyline. Because the effect was independent of response status we suggest
      that this increase reflects an effect of lithium that is independent from the
      psychopathological state or its change. This effect might be explained by the
      serotonergic effects of lithium.

PMID- 12225705
TI  - Effects of cigarette smoking and nicotine nasal spray on psychiatric symptoms and
      cognition in schizophrenia.
AB  - Schizophrenic patients have among the highest rates of smoking of any group of
      patients. Previous studies have identified psychophysiological and potential
      nicotinic receptor abnormalities which may be associated with this phenomenon.
      The effects of acute smoking or acute administration of nicotine nasal spray,
      after smoking abstinence, on negative symptoms and neurocognitive function have
      been less extensively studied in experimental designs. This study investigated
      the effects of smoking of high nicotine or denicotinized cigarettes, and
      receiving active or placebo nicotine nasal sprays, on positive and negative
      symptoms and cognitive functions in schizophrenic patients. The study utilized a
      placebo controlled crossover experimental design with pre- and post-drug
      evaluations on each experimental day. Smoking high nicotine cigarettes decreased
      negative symptoms more than denicotinized cigarettes, but smoking neither
      cigarette changed scores of positive symptoms, anxiety, or depression. Active
      nicotine nasal spray did not differentially decrease negative symptoms compared
      with placebo, but did improve performance on a spatial organization task, and
      tended to improve some measures of verbal memory and two-choice reaction time in
      schizophrenic patients. Both high and denicotinized cigarettes improved
      performance on the spatial processing task, but there was no statistically
      significant differential drug (Cigarette type) effect. These results suggest that
      acute smoking of cigarettes may transiently decrease negative symptoms in
      patients with schizophrenia, but it is unclear whether this effect is
      attributable to nicotine, other components of cigarettes, or the act of smoking.
      Nicotine nasal spray may modestly improve some selected aspects of cognitive
      function in schizophrenia.

PMID- 12225706
TI  - Pathophysiology and management of right heart ischemia.
AB  - Acute right coronary artery occlusion proximal to the right ventricular (RV)
      branches results in right ventricular free wall dysfunction, exerting
      mechanically disadvantageous effects on biventricular performance. Depressed RV
      systolic function decreases transpulmonary delivery of left ventricular (LV)
      preload, resulting in diminished cardiac output. The ischemic right ventricle is
      stiff, dilated, and volume dependent, resulting in pandiastolic RV dysfunction
      and septally mediated alterations in LV compliance, which are exacerbated by
      elevated intrapericardial pressure. Under these conditions, RV pressure
      generation and output are dependent on LV-septal contractile contributions,
      governed by both primary septal contraction and paradoxical septal motion. When
      the culprit coronary lesion is distal to the right atrial (RA) branches,
      augmented RA contractility enhances RV performance and optimizes cardiac output.
      Conversely, more proximal occlusions result in ischemic depression of RA
      contractility, which impairs RV filling and performance, resulting in more severe
      hemodynamic compromise. Bradyarrhythmias limit output generated by the rate
      dependent noncompliant ventricles. Hemodynamic compromise may respond to volume
      resuscitation and restoration of physiologic rhythm. Vasodilators and diuretics
      should generally be avoided. In some patients, parenteral inotropic stimulation
      may be required. The right ventricle appears to be relatively resistant to
      infarction and recovers even after prolonged occlusion. The term RV "infarction"
      appears to be somewhat of a misnomer, for in most patients acute RV dysfunction
      represents ischemic but predominantly viable myocardium. Although RV performance
      improves spontaneously even in the absence of reperfusion, recovery of function
      may be slow and associated with high in-hospital mortality. Reperfusion enhances
      recovery of RV performance and improves the clinical course and survival.

PMID- 12225707
TI  - Statin treatment following coronary artery stenting and one-year survival.
AB  - OBJECTIVES: We assessed the influence of statin therapy given after the procedure
      on one-year survival of patients treated with coronary artery stenting.
      BACKGROUND: Coronary artery stenting is currently a common treatment option for
      patients with symptomatic coronary artery disease (CAD). Although several
      secondary prevention trials have demonstrated improved survival achieved with
      statin therapy in conservatively treated patients with CAD, it is not known
      whether this benefit can also be expected in patients undergoing percutaneous
      coronary interventions with intraluminal stenting. METHODS: This study included
      4,520 patients younger than 80 years who underwent coronary artery stenting and
      were discharged from the hospital in the period October 1995 through September
      1999. We compared one-year mortality of 3,585 patients who received statins after
      stenting with that of 935 patients who did not. RESULTS: The mortality rate at
      one year was 2.6% among patients who received statins and 5.6% among those who
      did not. Thus, statin therapy at discharge was associated with an unadjusted odds
      ratio (OR) of 0.46 (95% confidence interval [CI], 0.33 to 0.65), indicating a 54%
      reduction in the risk of death at one year. After adjusting for other covariates,
      the risk reduction associated with statin therapy was 49%, OR 0.51 (95% CI, 0.36
      to 0.71). This reduction was observable in most of the subgroups of patients.
      CONCLUSIONS: The results of this nonrandomized study show that statin therapy
      improves survival after coronary artery stenting independent of patient
      characteristics recorded on the day of the intervention.

PMID- 12225708
TI  - Deoxyribonucleic acid damage in human lymphocytes after percutaneous transluminal
      coronary angioplasty.
AB  - OBJECTIVES; We investigated the presence of oxidative deoxyribonucleic acid (DNA)
      damage in the peripheral lymphocytes of patients undergoing percutaneous
      transluminal coronary angioplasty (PTCA) by using the micronucleus test and comet
      assay, which are sensitive biomarkers of DNA damage. BACKGROUND; Although it has
      recognized that ischemia-reperfusion can induce oxidative DNA damage, its
      occurrence in patients undergoing PTCA has not yet been demonstrated. METHODS:
      Three groups of patients were enrolled: 30 patients with documented coronary
      heart disease who underwent elective PTCA (group I); 25 patients who underwent
      elective coronary angiography for diagnostic purpose (group II); and 27 healthy,
      age- and gender-matched subjects (group III). For each subject, the frequency of
      micronucleated binucleated (MNBN) cells, DNA single-strand breaks (SSBs),
      endonuclease III-sensitive sites, and sites sensitive to formamidopyrimidine
      glycosylase (FPG) were analyzed before and after diagnostic procedures. RESULTS:
      The mean basal values of MNBN cells (p = 0.04), DNA-SSBs (p = 0.001),
      endonuclease III-sensitive sites (p = 0.002), and FPG sites (p < 0.0001) were
      significantly higher in groups I and II than in group III. A high significant
      increase of MNBN cell frequency was observed in group I after the PTCA procedure
      (11.0 +/- 1.3 vs. 19.8 +/- 1.6, p < 0.0001), whereas no significant difference
      was observed in group II (10.2 +/- 1.3 vs. 12.9 +/- 1.4, p = 0.18). A significant
      positive correlation was observed between the increase in the MNBN cell rate and
      total inflation time during PTCA (R = 0.549, p = 0.0017). The levels of DNA-SSBs
      (11.7 +/- 1.4 vs. 26.5 +/- 3.0, p = 0.0003) and FPG sites (13.8 +/- 1.8 vs. 22.5
      +/- 2.4, p = 0.01) were also higher after PTCA. CONCLUSIONS: Our results provide
      evidence for oxidative DNA damage after PTCA, likely related to ischemia
      reperfusion injury.

PMID- 12225709
TI  - Late intervention after anterior myocardial infarction: effects on left
      ventricular size, function, quality of life, and exercise tolerance: results of
      the Open Artery Trial (TOAT Study).
AB  - OBJECTIVE: We sought to conduct a randomized trial comparing late
      revascularization with conservative therapy in symptom-free patients after acute
      myocardial infarction (AMI). BACKGROUND: In the absence of ischemia, the benefits
      of reperfusion late after AMI remain controversial. However, the possibility
      exists that an open infarct related artery benefits healing post AMI. METHODS: Of
      223 patients enrolled with Q-wave anterior AMI, 66 with isolated persistent
      occlusion of the left anterior descending coronary artery (LAD) were randomized
      to the following treatments: 1) medical therapy (closed artery group; n = 34) or
      2) late intervention and stent to the LAD + medical therapy (open artery group; n
      = 32). The study was powered to compare left ventricular (LV) end-systolic volume
      between the two groups 12 months post AMI. RESULTS: Late intervention 26 +/- 18
      days post AMI resulted in significantly greater LV end-systolic and end-diastolic
      volumes at 12 months than medical therapy alone (106.6 +/- 37.5 ml vs. 79.7 +/-
      34.4 ml, p < 0.01 and 162.0 +/- 51.4 ml vs. 130.1 +/- 46.1 ml, p < 0.01,
      respectively). Exercise duration and peak workload significantly increased in
      both groups from 6 weeks to 12 months post AMI, although absolute values were
      greater in the open artery group. Quality of life scores tended to deteriorate
      during this time interval in the closed artery patients but remained unchanged in
      the open artery patients. Coronary angiography at 1 year documented a low
      incidence of intergroup cross-over (spontaneous recanalization in 19% and closure
      in 11%). CONCLUSIONS: In the present study, recanalization of occluded infarct
      related arteries in symptom-free patients approximately 1 month post AMI had an
      adverse effect on remodeling but tended to increase exercise tolerance and
      improve quality of life.

PMID- 12225710
TI  - Coronary vasodilator reserve: a clue to the explanation of (201)Tl redistribution
      patterns early after successful primary stenting for acute myocardial infarction.
AB  - OBJECTIVES: We sought to assess the mechanism and significance of different
      (201)Tl redistribution patterns after successful primary stenting following acute
      myocardial infarction (AMI). BACKGROUND: The mechanism of (201)Tl reverse
      redistribution and the impact of different redistribution patterns on the
      recovery of contractility after successful reperfusion therapy for AMI remain
      unclear. METHODS: We studied 41 consecutive patients with successful primary
      stenting for a first AMI. Patients underwent predischarge and six-month follow-up
      dipyridamole stress-reinjection single photon emission tomography (SPECT),
      coronary and left ventricular angiography. Intracoronary Doppler assessment of
      coronary flow reserve (CFR) was performed before discharge. RESULTS: Four patient
      groups were identified according to predischarge SPECT: patients with I:
      nonreversible defects (n = 8), II: redistribution (n = 7), III: reverse
      redistribution (n = 21), IV: no defect (n = 5). At follow-up contractility
      recovery increased in a stepwise fashion from groups I to IV (19 +/- 41%, 40 +/-
      53%, 70 +/- 28%, 78 +/- 33%, p = 0.01). Compared with patients with
      redistribution, those with reverse redistribution had lower infarct-related
      artery (IRA) CFR (2.2 +/- 0.5 vs. 2.8 +/- 0.9, p = 0.03) but higher contractility
      recovery. CONCLUSIONS: Variable (201)Tl redistribution patterns, early after
      successful stenting for AMI, may predict different degrees of late contractility
      recovery. The lower IRA CFR and the higher contractility recovery in areas with
      reverse redistribution suggest more severe microvascular dysfunction and less
      severe myocardial injury in such areas compared with those with redistribution.

PMID- 12225711
TI  - Predictive factors for early cardiac events and angiographic restenosis after
      coronary stent placement in small coronary arteries.
AB  - OBJECTIVES: The rationale of this study was to identify risk factors that predict
      early thrombotic events and angiographic restenosis after stenting in small
      coronary arteries. BACKGROUND: Rates of cardiac complications and restenosis
      after percutaneous coronary intervention are higher in patients with small versus
      large coronary arteries. Because of discordant results, randomized studies
      comparing stent placement with balloon angioplasty could not establish the best
      interventional approach to use in this high-risk subset of patients. This study
      of predictive factors, with special focus on stent design, may provide particular
      help in this regard. METHODS: Clinical, lesion-related, and procedural data of a
      large and unselected population of 3,156 consecutive patients were analyzed in a
      logistic regression model for both early and late complications. Repeat
      angiography at six months was performed in 80.8% of eligible patients. RESULTS:
      The strongest risk factors for early thrombotic events (cumulative incidence of
      4.2%) were the presence of an acute coronary syndrome and reduced left
      ventricular function. The stent design had no influence on early thrombotic
      complications. Restenosis (overall rate of 38.4%) was predominantly influenced by
      procedure-related variables, including the stent design and stented segment
      length. The incidence of restenosis varied from 29.6% to 55.8%, depending on the
      stent design used. CONCLUSIONS: Clinical factors known before the procedure are
      predominant risk factors for early thrombotic complications, underscoring the
      need for potent antiplatelet regimens in these patients. In contrast, our
      findings suggest a major impact of procedural factors, including the choice of
      stent type, on restenosis.

PMID- 12225712
TI  - Feasibility and efficacy of balloon-based neuroprotection during carotid artery
      stenting in a single-center setting.
AB  - We sought to prospectively assess the feasibility and in-hospital efficacy of the
      PercuSurge GuardWire temporary balloon-occlusive system for neuroprotection
      during carotid angioplasty and stenting (CAS).Carotid angioplasty and stenting
      harbors a risk of distal embolization. Cerebral protection devices are currently
      under clinical investigation.Ninety-six consecutive patients with carotid
      bifurcation disease underwent a total of 102 CAS procedures with the intention to
      use the GuardWire for neuroprotection. GuardWire deployment was achieved in 99
      procedures performed in 93 patients (97%). Device failure (n = 3) and severe
      neurologic responses to balloon occlusion of the targeted carotid artery (n = 2)
      accounted for five additional procedures that were essentially concluded without
      neuroprotection, for a total of 94 procedures completed as intended in 88
      patients (92% procedural feasibility rate). Carotid angioplasty and stenting was
      performed successfully in 94 patients (100 procedures). There were no in-hospital
      deaths; but three patients (3.1%) sustained strokes, and two patients experienced
      transient ischemic attacks, for a total periprocedural complication rate of 5.2%.
      One major stroke occurred with the GuardWire in place, whereas two minor strokes
      were observed in patients in whom the device could not be deployed. Thus,
      successful neuroprotected CAS without major neurologic events was achieved in 87
      patients (91%). The GuardWire temporary balloon-occlusive system is feasible as
      an adjunct to CAS in the majority of patients. It is associated with a 3.1% rate
      of major periprocedural neurologic complications. Adverse neurologic reactions to
      balloon occlusion may prohibit effective use of the system in about 2% of
      patients.

PMID- 12225713
TI  - Detection of coronary restenosis after coronary angioplasty by contrast-enhanced
      transthoracic echocardiographic Doppler assessment of coronary flow velocity
      reserve.
AB  - OBJECTIVES: This study sought to evaluate the diagnostic potential of contrast
      enhanced transthoracic echocardiography (CE-TTE) during adenosine infusion, a
      noninvasive method for evaluating coronary flow reserve (CFR), in detecting
      restenosis after successful percutaneous transluminal coronary angioplasty
      (PTCA). BACKGROUND: Restenosis is the most important limitation of PTCA, and CFR
      can be impaired in patients with angiographically documented significant coronary
      stenosis. METHODS: We performed 6 +/- 2 months of follow-up of 53 patients after
      successful elective PTCA in the left anterior descending coronary artery (LAD).
      Coronary angiography was performed at the end of the planned follow-up period or
      even before, if clinically indicated. Thus, of the 53 patients, a total of 63
      angiographic studies were performed; CE-TTE assessment of CFR was achieved before
      each of the 63 angiographic studies. RESULTS: Coronary angiography revealed the
      presence of restenosis (defined as >50% stenosis at a previous PTCA site) in 32
      angiographic examinations (group A) and no coronary restenosis in the remaining
      31 examinations (group B). Coronary flow reserve was significantly reduced in
      group A compared with group B (1.65 +/- 0.5 vs. 3.17 +/- 0.8, p < or = 0.001). A
      noninvasive CFR value < or = 2 was 93% specific and 78% sensitive for detecting
      significant restenosis, with positive and negative diagnostic accuracies of 92%
      and 80%, respectively. CONCLUSIONS: Noninvasive CFR assessment by CE-TTE is an
      accurate method of monitoring significant restenosis in the LAD when following up
      patients submitted to elective PTCA.

PMID- 12225714
TI  - Morphologic and angiographic features of coronary plaque rupture detected by
      intravascular ultrasound.
AB  - OBJECTIVES: This study was designed to report the clinical and angiographic
      correlates of plaque rupture detected by intravascular ultrasound (IVUS).
      BACKGROUND: Acute coronary syndromes result from spontaneous plaque rupture and
      thrombosis. METHODS: We report 300 plaque ruptures in 257 arteries in 254
      patients. Plaque ruptures were detected during pre-intervention IVUS. Standard
      clinical, angiographic, and IVUS parameters were collected and/or measured. One
      lesion per patient was analyzed. RESULTS: Multiple ruptures were observed in 39
      of 254 patients (15%), 36 in the same artery. Plaque rupture occurred not only in
      patients with unstable angina (46%) or myocardial infarction (MI, 33%), but also
      stable angina (11%) or no symptoms (11%). The tear in the fibrous cap could be
      identified in 157 of 254 patients; 63% occurred at the shoulder of the plaque and
      37% in the center of the plaque. Thrombi were more common in patients with
      unstable angina or MI (p = 0.02) and in multiple ruptures (p = 0.04). The plaque
      rupture site contained the minimum lumen area (MLA) site in only 28% of patients;
      rupture sites had larger arterial and lumen areas and more positive remodeling
      than MLA sites. Intravascular ultrasound plaque rupture strongly correlated with
      complex angiographic lesion morphology: ulceration in 81%, intimal flap in 40%,
      thrombus in 7%, and aneurysm in 7%. CONCLUSIONS: Plaque ruptures occur with
      varying clinical presentations, strongly correlate with angiographic complex
      lesion morphology, may be multiple, and usually do not cause lumen compromise.

PMID- 12225715
TI  - Exaggeration of nonculprit stenosis severity during acute myocardial infarction:
      implications for immediate multivessel revascularization.
AB  - OBJECTIVES: This study was designed to assess the prevalence and clinical
      significance of exaggerated nonculprit lesion stenosis in the setting of acute
      (<12 h) myocardial infarction (AMI). BACKGROUND: Although microvascular spasm may
      reduce nonculprit artery flow during AMI, it is unknown whether increased tone
      may exaggerate nonculprit lesion severity. METHODS: In patients with additional
      angiography within nine months of AMI, and significant nonculprit lesions imaged
      in matching views, stenosis severity was compared between studies in a random
      blinded fashion using validated quantitative coronary angiography software.
      Baseline demographics, medications, hemodynamics at each study, and clinical
      status at follow-up (infarct/unstable angina/stable angina) were used to
      determine the independent influence of the infarct presentation on stenosis
      exaggeration. RESULTS: From 548 patients with AMI (1/99 to 6/01, 321 with
      multivessel disease), 112 had additional angiography; of these 48 had 59 lesions
      suitable for analysis. Between infarct and noninfarct angiograms there was a
      significant change in minimal lumen diameter (1.53 +/- 0.51 mm vs. 1.78 +/- 0.65
      mm, p < 0.001) and percentage stenosis (49.3 +/- 14.5% vs. 40.4 +/- 16.6%, p <
      0.0001) of the nonculprit lesion without significant change in reference segment
      diameter, which was not predicted by changes in medication or hemodynamics.
      Twenty-one percent of patients had lesions >50% at AMI that were <50% at non-AMI
      angiography. Infarct versus noninfarct setting was the only significant
      independent predictor of change in nonculprit stenosis. CONCLUSIONS: Significant
      exaggeration of nonculprit lesion stenosis severity occurs at infarct
      angiography, which may affect revascularization decision making in an appreciable
      number of patients.

PMID- 12225717
TI  - Embolic complications of direct current cardioversion of atrial arrhythmias:
      association with low intensity of anticoagulation at the time of cardioversion.
AB  - OBJECTIVES: The goal of this study was to identify the factors responsible for
      embolic complications of direct current (DC) cardioversion of atrial arrhythmias.
      BACKGROUND: Direct current cardioversion of atrial fibrillation (AF) carries a
      risk of thromboembolism, which is reduced, but not eliminated, by
      anticoagulation. The risk of embolism after conversion of atrial flutter is
      believed to be lower. No series to date has included enough patients receiving
      anticoagulants or enough patients with atrial flutter to estimate the risk in
      these groups. METHODS: We reviewed the case records of 1,950 patients who
      underwent 2,639 attempts at DC cardioversion. RESULTS: Cardioversion was
      performed within two days of the apparent onset of the arrhythmia in 443
      episodes, 352 without subsequent prolonged anticoagulation with one embolic
      complication. Cardioversion was preceded by warfarin therapy for > or = 3 weeks
      in 1,932 instances. No embolic complication occurred in 779 attempts performed
      with an international normalized ratio (INR) of > or = 2.5 (95% confidence limits
      0% to 0.48%). Of 756 cases in which the INR was <2.5 or was not measured before
      conversion, nine were complicated by thromboembolism. Embolism was significantly
      more common at an INR of 1.5 to 2.4 than at an INR > or = 2.5 (0.93% vs. 0%, p =
      0.012). The incidence of embolism after conversion of atrial flutter or
      tachycardia was similar to that after cardioversion of AF (0.72% vs. 0.46%, p =
      NS). CONCLUSIONS: The INR should be > or = 2.5 at the time of cardioversion if
      the duration of AF is uncertain or >2 days. Cardioversion of atrial flutter
      presents similar risks and requires similar anticoagulation.

PMID- 12225716
TI  - Medical treatment of myocardial ischemia in coronary artery disease: effect of
      drug regime and irregular dosing in the CAPE II trial.
AB  - OBJECTIVES: The Circadian Anti-ischemia Program in Europe (CAPE II) compared the
      efficacy of amlodipine and diltiazem (Adizem XL) and the combination of
      amlodipine/atenolol and diltiazem (Adizem XL)/isosorbide 5-mononitrate on
      exercise and ambulatory myocardial ischemia during regular therapy and after
      omission of medication. BACKGROUND: The optimal medical therapy for ischemia
      suppression and the impact of irregular dosing using agents with different
      pharmacologic properties has not been established in patients with coronary
      disease. METHODS: Patients with > or = 4 ischemic episodes or > or = 20 min of ST
      segment depression on 72-h electrocardiogram were randomized to amlodipine 10 mg
      once daily or diltiazem (Adizem XL) 300 mg once daily in a 14-week double-blind
      randomized multicountry study. In the second phase, atenolol 100 mg was added to
      amlodipine and isosorbide 5-mononitrate 100 mg to diltiazem (Adizem XL).
      Ambulatory monitoring (72 h) and exercise testing were repeated after both
      phases, on treatment and after a 24-h drug-free interval. RESULTS: Both
      monotherapy with amlodipine and diltiazem (Adizem XL) were effective on symptoms
      and ambulatory and exercise ischemia. Combination therapy reduced ischemia
      further, with amlodipine/atenolol superior to diltiazem (Adizem XL)/isosorbide 5
      mononitrate. Amlodipine/atenolol was significantly superior during the drug-free
      interval with maintenance of ischemia reduction. CONCLUSIONS: Amlodipine, with
      its intrinsically long half-life alone or together with beta-blocker, is likely
      to produce superior ischemia reduction in clinical practice when patients
      frequently forget to take medication or dose irregularly.

PMID- 12225718
TI  - High intensity anticoagulation for cardioversion of atrial arrhythmias? The
      shocking truth.

PMID- 12225719
TI  - Relationship between obesity, insulin resistance, and coronary heart disease
      risk.
AB  - OBJECTIVES: The study goals were to: 1) define the relationship between body mass
      index (BMI) and insulin resistance in 314 nondiabetic, normotensive, healthy
      volunteers; and 2) determine the relationship between each of these two variables
      and coronary heart disease (CHD) risk factors. BACKGROUND: The importance of
      obesity as a risk factor for type 2 diabetes and hypertension is well-recognized,
      but its role as a CHD risk factor in nondiabetic, normotensive individuals is
      less well established. METHODS: Insulin resistance was quantified by determining
      the steady-state plasma glucose (SSPG) concentration during the last 30 min of a
      180-min infusion of octreotide, glucose, and insulin. In addition, nine CHD risk
      factors: age, systolic blood pressure, diastolic blood pressure (DBP), total
      cholesterol, triglycerides (TG), high-density lipoprotein (HDL) cholesterol and
      low-density lipoprotein cholesterol concentrations, and glucose and insulin
      responses to a 75-g oral glucose load were measured in the volunteers. RESULTS:
      The BMI and the SSPG concentration were significantly related (r = 0.465, p <
      0.001). The BMI and SSPG were both independently associated with each of the nine
      risk factors. In multiple regression analysis, SSPG concentration added modest to
      substantial power to BMI with regard to the prediction of DBP, HDL cholesterol
      and TG concentrations, and the glucose and insulin responses. CONCLUSIONS:
      Obesity and insulin resistance are both powerful predictors of CHD risk, and
      insulin resistance at any given degree of obesity accentuates the risk of CHD and
      type 2 diabetes.

PMID- 12225720
TI  - The big picture on obesity and insulin resistance.

PMID- 12225721
TI  - Coronary atherosclerosis in diabetes mellitus: a population-based autopsy study.
AB  - OBJECTIVES: The study was conducted to test the hypothesis that the prevalence of
      coronary atherosclerosis is greater among diabetic than among nondiabetic
      individuals and is similar for diabetic individuals without clinical coronary
      artery disease (CAD) and nondiabetics with clinical CAD. BACKGROUND: Persons with
      diabetes but without clinical CAD encounter cardiovascular mortality similar to
      nondiabetic individuals with clinical CAD. This excess mortality is not fully
      explained. We examined the association between diabetes and coronary
      atherosclerosis in a geographically defined autopsied population, while
      capitalizing on the autopsy rate and medical record linkage system available via
      the Rochester Epidemiology Project, which allows rigorous ascertainment of
      coronary atherosclerosis, clinical CAD, and diabetes. METHODS: Using two
      measures, namely a global coronary score and high-grade stenoses, the prevalence
      of atherosclerosis was analyzed in a cohort of autopsied residents of Rochester,
      Minnesota, age 30 years or older at death, while stratifying on diabetes,
      clinical CAD diagnosis, age, and gender. RESULTS: In this cohort, diabetes was
      associated with a higher prevalence of atherosclerosis. Among diabetic decedents
      without clinical CAD, almost three-fourths had high-grade coronary
      atherosclerosis and more than half had multivessel disease. Without diabetes,
      women had less atherosclerosis than men, but this female advantage was lost with
      diabetes. Among those without clinical CAD, diabetes was associated with a global
      coronary disease burden and a prevalence of high-grade atherosclerosis similar to
      that observed among nondiabetic subjects with clinical CAD. CONCLUSIONS: These
      findings provide mechanistic insights into the excess risk of clinical CAD among
      diabetic individuals, thereby supporting the need for aggressive prevention of
      atherosclerosis in all diabetic individuals, irrespective of clinical CAD
      symptoms.

PMID- 12225722
TI  - The impact of diabetes mellitus and prior myocardial infarction on mortality from
      all causes and from coronary heart disease in men.
AB  - OBJECTIVES: The goal of this study was to examine the impact of diabetes and
      prior myocardial infarction (MI) on mortality in men. BACKGROUND: Previous
      studies have suggested that a history of diabetes and a prior MI confer similar
      risk for subsequent fatal coronary heart disease (CHD). Few studies have examined
      duration of diabetes in relation to mortality. METHODS: We examined type 2
      diabetes and prior MI in relation to mortality among 51,316 men aged 40 to 75
      years in the Health Professionals Follow-up Study. RESULTS: During 10 years of
      follow-up, we documented 4,150 deaths from all causes, including 1,124 deaths
      from CHD. Compared with men without diabetes or prior MI at baseline, the
      multivariate relative risks (RRs) for fatal CHD were 3.84 (95% confidence
      interval [CI], 3.12 to 4.71) for those with diabetes only, 7.88 (95% CI, 6.86 to
      9.05) for those with MI only, and 13.41 (95% CI, 10.49 to 17.16) for those with
      both diabetes and MI. The corresponding RRs for total mortality were 1.91 (95%
      CI, 1.70 to 2.15), 2.23 (95% CI, 2.03 to 2.45), and 3.13 (95% CI, 2.56 to 3.84),
      respectively. Duration of diabetes was an independent risk factor for total as
      well as CHD mortality; the multivariate RRs of CHD mortality for increasing
      duration of diabetes (< or = 5 years, 6 to 10 years, 11 to 15 years, 16 to 25
      years, 26+ years) were 1.63, 1.93, 2.35, 2.31, and 3.87, respectively (p for
      trend <0.001), compared with nondiabetic participants. CONCLUSIONS: These
      findings support that both diabetes and MI are associated with elevated total and
      CHD mortality, and having both conditions is particularly hazardous. Longer
      duration of diabetes is a strong predictor of death among diabetic men.

PMID- 12225723
TI  - Marked bradykinin-induced tissue plasminogen activator release in patients with
      heart failure maintained on long-term angiotensin-converting enzyme inhibitor
      therapy.
AB  - OBJECTIVES: The aim of the present study was to assess the contribution of
      angiotensin-converting enzyme (ACE) inhibitor therapy to bradykinin-induced
      tissue-type plasminogen activator (t-PA) release in patients with heart failure
      (HF) secondary to ischemic heart disease. BACKGROUND: Bradykinin is a potent
      endothelial cell stimulant that causes vasodilatation and t-PA release. In large
      scale clinical trials, ACE inhibitor therapy prevents ischemic events. METHODS:
      Nine patients with symptomatic HF were evaluated on two occasions: during and
      following seven-day withdrawal of long-term ACE inhibitor therapy. Forearm blood
      flow was measured using bilateral venous occlusion plethysmography. Intrabrachial
      bradykinin (30 to 300 pmol/min), substance P (2 to 8 pmol/min), and sodium
      nitroprusside (1 to 4 pmol/min) were infused, and venous blood samples were
      withdrawn from both forearms for estimation of fibrinolytic variables. RESULTS:
      On both study days, bradykinin and substance P caused dose-dependent
      vasodilatation and release of t-PA from the infused forearm (p < 0.05 by analysis
      of variance [ANOVA]). Long-term ACE inhibitor therapy caused an increase in
      forearm vasodilatation (p < 0.05 by ANOVA) and t-PA release (p < 0.001 by ANOVA)
      during bradykinin, but not substance P, infusion. Maximal local plasma t-PA
      activity concentrations approached 100 IU/ml, and maximal forearm protein release
      was approximately 4.5 microg/min. CONCLUSIONS: Long-term ACE inhibitor therapy
      augments bradykinin-induced peripheral vasodilatation and local t-PA release in
      patients with HF due to ischemic heart disease. Local plasma t-PA activity
      concentrations approached those seen during systemic thrombolytic therapy for
      acute myocardial infarction. This may contribute to the primary mechanism of the
      anti-ischemic effects associated with long-term ACE inhibitor therapy.

PMID- 12225724
TI  - Tissue-type plasminogen activator release: new frontiers in endothelial function.

PMID- 12225725
TI  - Valsartan benefits left ventricular structure and function in heart failure: Val
      HeFT echocardiographic study.
AB  - OBJECTIVES: The objective of the study was to evaluate the effect of an
      angiotensin receptor blocker on left ventricular (LV) structure and function when
      added to prescribed heart failure therapy. BACKGROUND: The clinical benefit
      derived from heart failure therapy is attributed to the regression of LV
      remodeling. METHODS: At 302 multinational sites, 5,010 patients in New York Heart
      Association (NYHA) classification II to IV heart failure taking angiotensin
      converting enzyme inhibitor (ACEI) and/or beta-blocker (BB) were randomized into
      valsartan and placebo groups and followed for a mean of 22.4 months. Serial
      echocardiographic measurements of left ventricular internal diastolic diameter
      (LVIDd) and ejection fraction (EF) were recorded. Total study reproducibility
      calculated to 90% power at 5% significance defined detectable differences of 0.09
      cm for LVIDd and 0.86% for EF. RESULTS: Baseline LVIDd and EF for valsartan and
      placebo groups were similar: 3.6 +/- 0.5 versus 3.7 +/- 0.5 (cm/m(2)) and 26.6 +/
      7.3 versus 26.9 +/- 7.0 (%). Mean group changes from baseline over time were
      compared. Significant decrease in LVIDd and increase in EF began by four months,
      reached plateau by one year, and persisted to two years in valsartan compared
      with placebo patients, irrespective of age, gender, race, etiology, NYHA
      classification, and co-treatment therapy. Changes at 18 months were -0.12 +/- 0.4
      versus -0.05 +/- 0.4 (cm/m(2)), p < 0.00001 for LVIDd, and +4.5 +/- 8.9 versus
      +3.2 +/- 8.6 (%), p < 0.00001 for EF. The exception occurred in patients taking
      both ACEI and BB as co-treatment, in whom the decrease in LVIDd and increase in
      EF were no different between valsartan and placebo groups. CONCLUSIONS: The Val
      HeFT echocardiographic substudy of 5,010 patients with moderate heart failure
      demonstrated that valsartan therapy taken with either ACEI or BB reversed LV
      remodeling.

PMID- 12225726
TI  - Plasma brain natriuretic peptide concentration: impact of age and gender.
AB  - OBJECTIVES: We wished to examine the effects of age and gender on plasma brain
      natriuretic peptide (BNP) concentration in a population-based study. BACKGROUND:
      Measurement of BNP concentration is approved for use in the diagnosis of heart
      failure and may aid in the detection of left ventricular dysfunction. Although
      BNP is approved for clinical use, there are few data regarding the range of BNP
      observed in persons without cardiovascular disease or cardiac dysfunction. These
      data are essential for the interpretation of BNP. METHODS: In 2,042 randomly
      selected residents of Olmsted County, Minnesota, >44 years old, BNP (Shionogi and
      Biosite assays), Doppler echocardiography, and medical record review were
      performed. A normal subset of subjects (n = 767) in sinus rhythm without
      cardiovascular, renal, or pulmonary disease or diabetes; on no cardiovascular
      medications; and with normal systolic, diastolic, and valvular function was
      identified. RESULTS: Within the normal subset, the distribution of BNP differed
      by age, gender, and assay system. With both assays, BNP increased significantly
      with age and was significantly higher in women than men, leading to age-, gender
      , and assay-specific reference ranges. Receiver operating characteristic analysis
      for the ability of BNP to detect an ejection fraction < or = 40% was performed in
      each age/gender stratum in the entire cohort (n = 2,042) and confirmed that
      discriminatory values for BNP for detection of reduced ejection fraction were
      higher in women and older persons and were different between the two assays.
      CONCLUSIONS: Interpretation of BNP should include consideration of age-, gender-,
      and assay-specific partition values.

PMID- 12225727
TI  - Mechanisms of diastolic intraventricular regional pressure differences and flow
      in the inflow and outflow tracts.
AB  - OBJECTIVES: We sought to investigate the mechanisms of left ventricular (LV)
      intracavitary early diastolic flow during changes in contractility and loading.
      BACKGROUND: There is limited understanding of how intracavitary flow velocities
      relate to intraventricular driving pressures. METHODS: In 12 anesthetized dogs,
      we measured pressures in the left atrium (LA), LV at the mitral tip, apex, and
      subaortic region; intraventricular velocities by color M-mode Doppler
      echocardiography (CMD); and volume by sonomicrometry. We also investigated
      responses to isoprenaline, ischemic failure, and volume loading. RESULTS: During
      rapid, early filling, the mitral to apical pressure gradient (LVP(mitral-apex))
      correlated with the peak mitral to apical velocity (r = 0.92). The LVP(mitral
      apex) increased from 1.4 +/- 0.6 (SD) to 3.2 +/- 1.8 mm Hg during isoprenaline (p
      < 0.05) and decreased to 0.6 +/- 0.5 during ischemic failure (p < 0.01). The
      pressure gradient correlated positively with the time constant of isovolumic
      relaxation (tau) (r = 0.82) and negatively with LV end-systolic volume (ESV) (r =
      -0.77). Volume loading increased LA pressure, tau, and ESV, but caused no
      significant change in LVP(mitral-apex). At baseline and during isoprenaline, tau
      was shorter (p < 0.05) at the apex than at the base. When the mitral to apical
      gradient approached zero, filling velocities were directed toward the LV outflow
      tract, and a pressure gradient was established between the apex and subaortic
      region. CONCLUSIONS: Changes in LVP(mitral-apex) induced by inotropic stimuli,
      loading, and ischemia appeared to reflect dependency of the pressure gradient on
      the rate of relaxation, ESV, and LA pressure. Regional differences in the rate of
      relaxation may also contribute to intraventricular pressure gradients. These
      findings have implications for how to interpret intraventricular filling in a
      clinical context.

PMID- 12225728
TI  - Opening of the adenosine triphosphate-sensitive potassium channel attenuates
      cardiac remodeling induced by long-term inhibition of nitric oxide synthesis:
      role of 70-kDa S6 kinase and extracellular signal-regulated kinase.
AB  - OBJECTIVES: We examined whether the adenosine triphosphate (ATP)-sensitive
      potassium (K(ATP)) channel openers (KCOs) block myocardial hypertrophy and
      whether the 70-kDa S6 kinase (p70S6K) or extracellular signal-regulated kinase
      (ERK)-dependent pathway is involved. BACKGROUND: Long-term inhibition of nitric
      oxide (NO) synthesis induces cardiac hypertrophy independent of blood pressure,
      by increasing protein synthesis in vivo. The KCOs attenuate calcium overload and
      confer cardioprotection against ischemic stress, thereby preventing myocardial
      remodeling. METHODS: Twelve Wistar-Kyoto rat groups underwent eight weeks of the
      drug treatment in combination with the NO synthase inhibitor N(omega)-nitro-L
      arginine methyl ester (L-NAME), the inactive isomer D(omega)-nitro-L-arginine
      methyl ester, KCOs (nicorandil, 3 and 10 mg/kg per day, or JTV-506, 0.3 mg/kg per
      day), or the K(ATP) channel blocker glibenclamide. The L-NAME was also used with
      hydralazine, the p70S6K inhibitor rapamycin, or the mitogen-activated protein
      kinase inhibitor PD98059. Finally, the left ventricular weight (LVW) to body
      weight (BW) ratio was quantified, followed by histologic examination and kinase
      assay. RESULTS: The L-NAME increased blood pressure and LVW/BW, as compared with
      the control agent. The KCOs and hydralazine equally cancelled the increase in
      blood pressure, whereas only KCOs blocked the increase in LVW/BW and myocardial
      hypertrophy induced by L-NAME. The L-NAME group showed both p70S6K and ERK
      activation in the myocardium (2.3-fold and 2.0-fold increases, respectively), as
      compared with the control group, which was not reversed by hydralazine. Selective
      inhibition of either p70S6K or ERK blocked myocardial hypertrophy. The KCOs
      prevented the increase in activity only of p70S6K. Glibenclamide reversed the
      effect of nicorandil in the presence of L-NAME. CONCLUSIONS: The KCOs modulate
      p70S6K, not ERK, to attenuate myocardial hypertrophy induced by long-term
      inhibition of NO synthesis in vivo.

PMID- 12225729
TI  - Amelioration of ischemia- and reperfusion-induced myocardial injury by the
      selective estrogen receptor modulator, raloxifene, in the canine heart.
AB  - OBJECTIVES: We sought to investigate whether raloxifene reduces ischemia
      reperfusion injury and what mechanisms are involved in the cardioprotective
      effects. BACKGROUND: Estradiol-17-beta reduces myocardial infarct size in
      ischemia-reperfusion injury. Raloxifene, a selective estrogen receptor modulator,
      demonstrates immediate coronary artery vasorelaxing effects. METHODS: The
      myocardial ischemia-reperfusion model included anesthetized open-chest dogs after
      90-min occlusion of the left anterior descending coronary artery (LAD) and
      subsequent 6-h reperfusion. Raloxifene and/or other drugs were infused into the
      LAD from 10 min before coronary occlusion to 1 h after reperfusion without an
      occlusion period. RESULTS: Infarct size was reduced in the raloxifene (5
      microg/kg per min) group compared with the control group (7.2 +/- 2.5% vs. 40.9
      +/- 3.9% of the area at risk, p < 0.01). Either N(G)-nitro-L-arginine methyl
      ester (L-NAME), the inhibitor of nitric oxide (NO) synthase, or charybdotoxin,
      the blocker of Ca(2+)-activated K+ (K(Ca)) channels, partially attenuated the
      infarct size-limiting effect, and both of them completely abolished the effect.
      The incidence of ventricular fibrillation was also less in the raloxifene group
      than in the control group (11% vs. 44%, p < 0.05). Activity of p38 mitogen
      activated protein (MAP) kinase increased with 15-min ischemia, and raloxifene
      pretreatment inhibited the activity. Myeloperoxidase activity of the 6-h
      reperfused myocardium was also attenuated by raloxifene. CONCLUSIONS: These data
      demonstrate that raloxifene reduces myocardial ischemia-reperfusion injury by
      mechanisms dependent on NO and the opening of K(Ca) channels in canine hearts.
      Deactivation of p38 MAP kinase and myeloperoxidase by raloxifene may be involved
      in the cellular mechanisms of cardioprotection.

PMID- 12225731
TI  - Peer review: better than the alternatives.

PMID- 12225730
TI  - Pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase may
      represent a novel therapeutic approach in chronic heart failure.
AB  - OBJECTIVES: We investigated the effects of a novel ultrapotent poly(adenosine
      diphosphate-ribose) polymerase (PARP) inhibitor, PJ34, on cardiac and endothelial
      dysfunction in a rat model of chronic heart failure (CHF). BACKGROUND:
      Overactivation of the nuclear enzyme PARP importantly contributes to the
      development of cell dysfunction and tissue injury in various pathophysiologic
      conditions associated with oxidative stress, including myocardial reperfusion
      injury, heart transplantation, stroke, shock, and diabetes. METHODS: Chronic
      heart failure was induced in Wistar rats by chronic ligation of the left anterior
      descending coronary artery. Left ventricular (LV) function and ex vivo vascular
      contractility and relaxation were measured 10 weeks after the surgery.
      Nitrotyrosine (NT) formation and PARP activation were detected by
      immunohistochemistry. RESULTS: Chronic heart failure induced increased NT
      formation and PARP activation in the myocardium and intramural vasculature,
      depressed LV performance, and impaired vascular relaxation of aortic rings. PJ34
      significantly decreased myocardial PARP activation but not NT formation, and
      improved both cardiac dysfunction and vascular relaxation. CONCLUSIONS: Poly(ADP
      ribose) polymerase inhibition represents a novel approach for the experimental
      treatment of CHF.

PMID- 12225732
TI  - Family physicians and health care for adolescents.

PMID- 12225733
TI  - The relation between alcohol abuse or dependence and academic performance in
      first-year college students.
AB  - A large-scale study (N = 3,518) was designed to assess the academic performance
      of college freshmen in relationship to alcohol abuse or dependence. Alcohol abuse
      or dependence was identified in 501 (14%) students; of these, 128 (3.6%) were
      alcohol-dependent. Of the students who met criteria of alcohol dependence, 62.5%
      failed in their first year, compared to 50% among students who did not report
      these drinking problems.

PMID- 12225734
TI  - Psychosocial correlates of physical activity in white and African-American girls.
AB  - PURPOSE: To evaluate the relative utility of the Theory of Reasoned Action (TRA)
      and the Theory of Planned Behavior (TPB) in explaining intentions and physical
      activity behavior in white and African-American eighth-grade girls. METHODS: One
      thousand-thirty white and 1.114 African-American eighth-grade girls (mean age
      13.6 +/- 0.7 years) from 31 middle schools in South Carolina completed a 3-day
      physical activity recall and a questionnaire assessing attitudes, subjective
      norms, perceived behavioral control, self-efficacy, and intentions related to
      regular participation in moderate-to-vigorous physical activity (MVPA). RESULTS:
      Among Whites, 17% of the variance in intentions was contributed by subjective
      norms and attitude, with intentions accounting for 8% of the variance in MVPA.
      The addition of perceived behavioral control and self-efficacy to the TRA
      significantly improved the prediction of intentions and MVPA accounting for 40%
      and 10% of the variance, respectively. Among African-Americans, subjective norms
      and attitude accounted for 13% of the variance in intentions, with intentions
      accounting for only 3% of the variance in MVPA. The addition of perceived
      behavioral control and self-efficacy to the TRA significantly improved the
      prediction of intentions and MVPA accounting for 28% and 5% of the variance,
      respectively. CONCLUSIONS: The results provided limited empirical support for the
      TPB among white adolescent girls; however, our findings suggest that the planned
      behavior framework has limited utility among African-American adolescent girls.
      The relatively weak link between intentions and MVPA observed in both population
      groups suggest that constructs external to the TPB may be more important
      mediators of physical activity behavior in adolescent girls.

PMID- 12225735
TI  - HRQL and severity of brain ultrasound findings in a cohort of adolescents who
      were born preterm.
AB  - PURPOSE: To determine whether health-related quality of life (HRQL) in a cohort
      of adolescents who were born prematurely is related to the severity of brain
      ultrasound examination findings during the newborn period. METHODS: This study
      uses a historical, prospective methodology to investigate the 84 members of a
      cohort of infants born prematurely (<33 weeks gestation) at Thomas Jefferson
      University Hospital during a 25-month period, from 1979 to 1981. We extracted the
      following information from their neonatal intensive care unit (NICU) records:
      ultrasound examination findings (graded for intraventricular hemorrhage (IVH) and
      periventricular leukomalacia (PVL); and records of medical illness (respiratory,
      gastrointestinal, and other) during the NICU stay. We followed-up the members of
      this cohort 18-19 years later, obtaining data on 53 (63%). We correlated the NICU
      data with the following self-report outcome measures: HRQL, Disabilities
      Questionnaire [parental report indicating the severity of complications of
      prematurity (DISAB)] and psychological assessment tests [Beck Depression
      Inventory (BDI), Coopersmith Self-Esteem Inventory (CSEI), and Body Shape
      Questionnaire (BSQ)]. We used the method of multiple discriminant function
      analysis to determine statistical significance of differences between the two
      ultrasound groups, grades 0-2 IVH, no PVL vs. grades 3-4 IVH and/or PVL. RESULTS:
      A statistically significant difference was obtained between the two ultrasound
      groups (grades 0-2 IVH, no PVL vs. grades 3-4 IVH and/or PVL) among the HRQL
      variables (Wilks' lambda =.764, df = 5, p <.470). The relative contribution of
      dependent variables (HRQL1, HRQL2, HRQL3, HRQL4, DISAB) to the group separation
      was assessed through the interpretation of discriminant function-variable
      correlation. HRQL1 and DISAB made the largest discriminant between groups, which
      is supported by results from univariate Student's t-tests. Study subjects with
      grades 3-4 IVH and/or PVL ultrasound findings obtained much lower HRQL1 scores
      (better overall estimation of HRQL) and much higher DISAB scores than subjects
      with grades 0-2 IVH, no PVL ultrasound findings. CONCLUSIONS: It appears that the
      lower an adolescent's score on overall HRQL (HRQL1), (i.e., the better the self
      perceived overall quality of life), the more likely he or she displayed the
      higher severity of brain ultrasound examination findings during the NICU
      hospitalization. A larger study of premature infants who are followed into
      adolescence is required to better understand the factors that determine the
      association of IVH and PVL with HRQL.

PMID- 12225736
TI  - Association of adolescent risk behaviors with mental health symptoms in high
      school students.
AB  - PURPOSE: To examine the hypothesis that self-reported symptoms of depression and
      stress may be associated with other risk behaviors. METHODS: A secondary data
      analysis of the 1992 Massachusetts Adolescent Health Survey involving a
      representative sample of 2,224 ninth and twelfth grade students was performed.
      The dichotomous dependent variable was positive if the adolescent reported
      feeling depressed or stressed for 10 or more days in the past month. Potential
      independent variables examined were age, gender, race/ethnicity, and 14 risk or
      protective behaviors: each scored on a seven point scale representing increasing
      frequency of a behavior in the past month. A four-level sexual risk variable was
      constructed as well. Associations were assessed using Chi-square, and
      phi/contingency coefficients, and logistic regression analyses to predict the
      odds of reporting depression/stress. RESULTS: The mean age of the sample was 16.2
      +/- 1.6 years; 52% males; 78% were white, 9% black, 6% Latino, 2% Asian, and 4%
      other racial/ethnic heritage; 35% reported feeling depressed/stressed > or = 10
      days in the past month. A logistic regression model found that feelings of
      depression/stress were associated with increasing age (OR = 1.09 with each
      additional year [95% CI, 1.02-1.18]), female gender (3.28 [2.62-4.12]);
      increasing levels of tobacco use (1.07 [1.01-1.12]), physical fights (1.19 [1.11
      1.28]); and non-use of birth control compared with never having been sexually
      active (1.81 [1.31-2.49]). Independent variables of reporting depression/stress
      for males included increasing age (1.15 [1.03-1.28]), and physical fights (1.20
      [1.10-1.30]), and non-use of birth control compared with never sexually active
      (1.91 [1.28-2.92]). Independent risk and protective factors for females included
      tobacco use (1.10 [1.02-1.19]), healthy diet (0.89 [0.83- 0.96]), and always
      (1.49 [1.03-2.28]) or sometimes used birth control (1.56 [1.03-1.28]) compared
      with never sexually active. CONCLUSIONS: Female gender had greater than threefold
      increased odds of reporting depression/stress. Other associations, with some
      gender differences, include older age, physical fights, non-use of birth control,
      lack of a healthy diet, and use of tobacco.

PMID- 12225737
TI  - Reliability and validity of the youth asset survey (YAS).
AB  - PURPOSE: To describe the construction of a survey that was developed to measure
      youth assets. The paper details the ten youth developmental assets measures
      within the survey, including the psychometric properties of those measures
      derived from factor analysis and reliability testing. METHODS: Three studies were
      conducted, including a study of 1,350 randomly selected youth (mean age = 15.4
      years; 52% female; 47% white, 22% black, 19% Hispanic, 10% Native American),
      using in-person interviews, to develop an asset instrument tool. Factor analysis
      was performed on a correlation matrix, using principal axis factoring, and
      varimax rotation. The criteria were set to extract eight factors. RESULTS: The
      eight factors extracted represented six developmental assets as originally
      defined, including Family Communication, Peer Role Models, Future Aspirations,
      Responsible Choices, Community Involvement, and Non-Parental Role Models. One
      asset (Constructive Use of Time) was split into two specific assets:
      groups/sports and religious time. Two assets did not form factors (Good Health
      Practices [exercise/nutrition] and Cultural Respect) and were defined as one-item
      assets. All factor loading scores were.40 or higher and all Cronbach alphas
      were.60 or higher. CONCLUSIONS: Factor analyses suggest that the constructs are
      reliable measures of youth developmental assets. The psychometrically sound asset
      measures presented here will provide scientists with valid and reliable
      instruments to assess and compare the prevalence of youth assets across
      populations and to investigate potential relationships between youth assets and
      other outcomes, such as youth risk behaviors.

PMID- 12225738
TI  - Mothers' influence on the timing of first sex among 14- and 15-year-olds.
AB  - PURPOSE: To better understand maternal influence on the timing of first sex for
      adolescents. METHODS: Using data from the National Longitudinal Study of
      Adolescent Health, Cox proportional hazard models were used to assess the
      association between maternal characteristics and the timing of first sex. Matched
      dyads of mothers and their adolescent children were used. RESULTS: Of the 2,006
      adolescents aged 14 and 15 years who reported to be virgins, 95 males (10.8%) and
      162 females (15.8%) indicated they had initiated sex within the follow-up period,
      1 year later. For males, few variables beyond the controls used in the models
      were predictive of timing of first sexual intercourse. For females, mother's
      satisfaction with her relationship with her daughter (hazard ratio =.62),
      mother's strong disapproval of her daughter having sex (hazard ratio =.56), and
      frequency of communication with the parents of her daughter's friends were
      associated with later sexual debut (hazard ratio =.88). CONCLUSION: Based on the
      variables in the model, mothers' values and beliefs and relationship satisfaction
      have more influence on daughters than on sons.

PMID- 12225739
TI  - Young, disadvantaged fathers' involvement with their infants: an ecological
      perspective.
AB  - PURPOSE: To investigate fathers' involvement with their children using an
      ecological model, multiple respondents, and a comprehensive definition of
      fathers' involvement. The study's primary objectives were: (a) to describe the
      characteristics of fathers whose infants are born to low-income, urban, African
      American adolescent mothers; (b) to describe the ways in which fathers are
      involved with their children; and (c) to identify factors associated with
      fathers' involvement. METHODS: A total of 181 first-time mothers (aged <18 years)
      living in three-generation households (infant, mother, and grandmother) were
      recruited from three urban hospitals shortly after delivery and invited to
      participate in a longitudinal study of parenting. Mothers provided the name of
      their infant's father; 109 (60%) of the fathers also agreed to participate.
      Baseline interviews of mothers, fathers, and grandmothers addressed demographic
      characteristics, relationships, and the father's involvement with his child.
      RESULTS: Three multivariate regression models were used to identify factors
      associated with paternal involvement, explaining 35% to 51% of the variability in
      father involvement. Regardless of the respondent (mother, father, or
      grandmother), paternal involvement was predicted most strongly by the quality of
      the parents' romantic relationship. The father's employment status, the maternal
      grandmother's education, and the father's relationship with the baby's maternal
      grandmother were also associated with paternal involvement. CONCLUSIONS: The
      study confirmed the value of an ecological perspective that uses multiple
      informants and a comprehensive definition of father involvement that includes
      multiple role functions. Efforts to increase paternal involvement should help
      young parents separate the father's relationship with their child from the
      romantic relationship between the mother and father, address the roles played by
      maternal grandmothers, and assist fathers to complete their education, and obtain
      and keep jobs.

PMID- 12225740
TI  - Impact of an empowerment-based parent education program on the reduction of youth
      suicide risk factors.
AB  - PURPOSE: To evaluate the impact of parent education groups on youth suicide risk
      factors. The potential for informal transmission of intervention impacts within
      school communities was assessed. METHODS: Parent education groups were offered to
      volunteers from 14 high schools that were closely matched to 14 comparison
      schools. The professionally led groups aimed to empower parents to assist one
      another to improve communication skills and relationships with adolescents.
      Australian 8th-grade students (aged 14 years) responded to classroom surveys
      repeated at baseline and after 3 months. Logistic regression was used to test for
      intervention impacts on adolescent substance use, deliquency, self-harm behavior,
      and depression. There were no differences between the intervention (n = 305) and
      comparison (n = 272) samples at baseline on the measures of depression, health
      behavior, or family relationships. RESULTS: Students in the intervention schools
      demonstrated increased maternal care (adjusted odds ratio [AOR] 1.9), reductions
      in conflict with parents (AOR.5), reduced substance use (AOR.5 to.6), and less
      delinquency (AOR.2). Parent education group participants were more likely to be
      sole parents and their children reported higher rates of substance use at
      baseline. Intervention impacts revealed a dose-response with the largest impacts
      associated with directly participating parents, but significant impacts were also
      evident for others in the intervention schools. Where best friend dyads were
      identified, the best friend's positive family relationships reduced subsequent
      substance use among respondents. This and other social contagion processes were
      posited to explain the transfer of positive impacts beyond the minority of
      directly participating families. CONCLUSIONS: A whole-school parent education
      intervention demonstrated promising impacts on a range of risk behaviors and
      protective factors relevant to youth self-harm and suicide.

PMID- 12225741
TI  - Correlates of marijuana use in Colombian adolescents: a focus on the impact of
      the ecological/cultural domain.
AB  - To examine the influence of ecological/cultural factors and family, personality,
      and peer factors present during early adolescence that influence marijuana use in
      late adolescence. A community sample of 2,226 Colombian adolescents living in
      mixed urban-rural communities and their mothers were interviewed in their homes
      by trained Colombian interviewers, first in 1995-1996 and then again 2 years
      later. The scales used were based on item intercorrelations and grouped into the
      following categories: (a) adolescent personality, (b) family traits, (c) peer
      factors, (d) ecological/cultural variables, and (e) marijuana use. Data were
      examined using hierarchical regression modeling to determine the relationship
      between each of the domains and late adolescent marijuana use. The findings
      supported the family interactional theory of adolescent drug use behavior and
      found that factors in all of the domains had a direct effect on late adolescent
      marijuana use as well as indirect effects mediated through the more proximal
      domains in the model. Of particular interest was the strength of the influence of
      the ecological/cultural factors, which far exceeded that observed in similar
      studies done in the United States. Owing to the similarity with findings from
      studies conducted in the United States, interventions designed domestically could
      effectively be directly applied to adolescents in Colombia. The findings also
      suggest that prevention programs designed specifically to target ecological or
      cultural factors may have the most profound influence for reducing marijuana use
      in late adolescence.

PMID- 12225742
TI  - The apomyoglobin folding pathway revisited: structural heterogeneity in the
      kinetic burst phase intermediate.
AB  - Extensive analysis of accurate quench-flow hydrogen exchange results indicates
      that the burst phase kinetic intermediate in the folding of apomyoglobin (apoMb)
      from urea is structurally heterogeneous. The structural variability is associated
      with the partial folding of the E helix during the burst phase (<6.4ms) of the
      folding process. Analysis of the effects of exchange-out of amide proton labels
      during the labeling pulse ( approximately pH 10) of the quench-flow process
      indicates that three of the amide protons in the E helix are in fact largely
      protected in the burst phase of folding, while the remainder of the E helix has a
      substantial complement of amide protons that show biphasic kinetics, i.e. are
      protected partly during the burst phase and partly during the slow phase of
      folding. The locations of these amide protons can be used to map the sites of
      structural heterogeneity in the kinetic molten globule. These sites include,
      besides the E helix, the ends of the A and B helices and part of the C helix. Our
      results give significant support to the hypothesis that the kinetic molten
      globule intermediate of apoMb is native-like.

PMID- 12225743
TI  - Chirality-independent protein-protein recognition between transmembrane domains
      in vivo.
AB  - Stereospecificity in protein-protein recognition and docking is an unchallenged
      dogma. Soluble proteins provide the main source of evidence for
      stereospecificity. In contrast, within the membrane little is known about the
      role of stereospecificity in the recognition process. Here, we have reassessed
      the stereospecificity of protein-protein recognition by testing whether it holds
      true for the well-defined glycophorin A (GPA) transmembrane domain in vivo. We
      found that the all-D amino acid GPA transmembrane domain and two all-D mutants
      specifically associated with an all-L GPA transmembrane domain, within the
      membrane milieu of Escherichia coli. Molecular dynamics techniques reveal a
      possible structural explanation to the observed interaction between all-D and all
      L transmembrane domains. A very strong correlation was found between amino acid
      residues at the interface of both the all-L homodimer structure and the mixed L/D
      heterodimer structure, suggesting that the original interactions are conserved.
      The results suggest that GPA helix-helix recognition within the membrane is
      chirality-independent.

PMID- 12225744
TI  - Evaluation of C-H cdots, three dots, centered O hydrogen bonds in native and
      misfolded proteins.
AB  - Non-traditional C-H cdots, three dots, centered Y hydrogen bonds, in which a
      carbon atom acts as the hydrogen donor and an electronegative atom Y (Y=N, O or
      S) acts as the acceptor, have been reported in proteins, but their importance in
      protein structures is not well established. Here, we present the results of three
      computational tests that examine the significance of C-H cdots, three dots,
      centered Y bonds involving the C(alpha) in proteins. First, we compared the
      number of C(alpha)-H cdots, three dots, centered Y bonds in native structures
      with two sets of compact, energy-minimized decoy structures. The decoy structures
      contain about as many C(alpha)-H cdots, three dots, centered Y bonds as the
      native structures, indicating that the constraints of chain connectivity and
      compactness can lead to incidental formation of C(alpha)-H cdots, three dots,
      centered Y bonds. Secondly, we examined whether short C(alpha)-H cdots, three
      dots, centered Y bonds have a tendency to be linear, as is expected for a
      cohesive hydrogen-bonding interaction. The native structures do show this trend,
      but so does one of the decoy sets, suggesting that this criterion is also not
      sufficient to indicate a stabilizing interaction. Finally, we examined the
      preference for C(alpha)-H cdots, three dots, centered Y bond donors to be near to
      strong hydrogen bond acceptors. In the native proteins, the alpha protons attract
      strong acceptors like oxygen atoms more than weak acceptors. In contrast,
      hydrogen bond donors in the decoy structures do not distinguish between strong
      and weak acceptors. Thus, any individual C(alpha)-H cdots, three dots, centered Y
      bond may be fortuitous and occur due to the polypeptide connectivity and
      compactness. Taken collectively, however, C(alpha)-H cdots, three dots, centered
      Y bonds provide a weakly cohesive force that stabilizes proteins.

PMID- 12225745
TI  - Active Escherichia coli transcription elongation complexes are functionally
      homogeneous.
AB  - The elongation phase of RNA transcription represents a major target for the
      regulation of gene expression. Two general classes of models have been proposed
      to define the dynamic properties of transcription complexes in the elongation
      phase. Stable heterogeneity models posit that the ensemble of active elongation
      competent complexes consists of multiple distinct and stable forms that are
      specified early in the transcription cycle and isomerize to other forms slowly.
      In contrast, equilibrium or rapid interconversion models require that active
      elongation complexes interconvert rapidly on the time-scale of single nucleotide
      addition. Measurements of transcription termination efficiency (TE) can be used
      to distinguish between these models, because stable heterogeneity models predict
      that the termination-resistant fraction of an elongation complex population
      should be enriched after transcription through an upstream terminator, leading to
      a decreased TE at downstream terminators. In contrast, rapid interconversion
      models require that the population of active (elongation-competent) complexes
      equilibrate after transcription through each terminator and, therefore, that the
      value of TE observed at identical upstream and downstream terminators should be
      the same. We have constructed transcription templates containing multiple
      identical terminators and found no significant changes in TE with terminator
      position along the template. Various other forms of upstream treatment of
      elongation complex populations also were used to attempt to fractionate the
      complexes into functionally different forms. None of these treatments changed the
      apparent TE at downstream terminators. These results are consistent with a rapid
      interconversion model of transcript elongation. The consequences of these results
      for the regulation of gene expression are discussed.

PMID- 12225746
TI  - The TRTGn motif stabilizes the transcription initiation open complex.
AB  - The effect on transcription initiation by the extended -10 motif (5'-TRTG(n)-3'),
      positioned upstream of the -10 region, was investigated using a series of base
      substitution mutations in the alpha-amylase promoter (amyP). The extended -10
      motif, previously referred to as the -16 region, is found frequently in Gram
      positive bacterial promoters and several extended -10 promoters from Escherichia
      coli. The inhibitory effects of the non-productive promoter site (amyP2), which
      overlaps the upstream region of amyP, were eliminated by mutagenesis of the -35
      region and the TRTG motif of amyP2. Removal by mutagenesis of the competitive
      effects of amyP2 resulted in a reduced dependence of amyP on the TRTG motif. In
      the absence of the second promoter, mutations in the TRTG motif of amyP
      destabilized the open complex and prevented the maintenance of open complexes at
      low temperatures. The open complex half-life was up to 26-fold shorter in the
      mutant TRTG motif promoters than in the wild-type promoter. We demonstrate that
      the amyP TRTG motif dramatically stabilizes the open complex intermediate during
      transcription initiation. Even though the open complex is less stable in the
      mutant promoters, the region of melted DNA is the same in the wild-type and
      mutant promoters. However, upon addition of the first three nucleotides, which
      trap RNAP (RNA polymerase) in a stable initiating complex, the melted DNA region
      contracts at the 5'-end in a TRTG motif promoter mutant but not at the wild-type
      promoter, indicating that the motif contributes to maintaining DNA-strand
      separation.

PMID- 12225747
TI  - A functional role for correlated motion in the N-terminal RNA-binding domain of
      human U1A protein.
AB  - The N-terminal RNA-binding domain of the human U1A protein (RBD1) undergoes local
      conformational changes upon binding to its target RNA. Here, the wild-type RBD1
      and two mutants are examined with molecular dynamics simulations that are
      analyzed using the reorientational eigenmode dynamics (RED) formalism. The
      results reveal changes in the magnitude and extent of coupled intra-domain
      motions resulting from single amino acid substitutions. Interpretation of the
      novel RED results and corresponding NMR relaxation data suggests that the loss of
      collective motions in the mutants could account for their weak RNA-binding.

PMID- 12225748
TI  - Structure and stability of wild-type and mutant RNA internal loops from the SL-1
      domain of the HIV-1 packaging signal.
AB  - The packaging signal (Psi) of the human immunodeficiency virus type 1 (HIV-1)
      enables encapsidation of the full-length genomic RNA against a background of a
      vast excess of cellular mRNAs. The core HIV-1 Psi is approximately 109
      nucleotides and contains sequences critical for viral genomic dimerisation and
      splicing, in addition to the packaging signal. It consists of a series of stem
      loops (termed SL-1 to SL-4), which can be arranged in a cloverleaf secondary
      structure. Using a combination of NMR spectroscopy, UV melting experiments,
      molecular modeling and phylogenetic analyses, we have explored the structure of
      two conserved internal loops proximal to the palindromic sequence of SL-1.
      Internal loop A, composed of six purines, forms a flexible structure that is
      strikingly similar to the Rev responsive element motif when bound to Rev protein.
      This result suggests that it may function as a protein-binding site. The
      absolutely conserved four-purine internal loop B is instead conformationally and
      thermodynamically unstable, and exhibits multiple conformations in solution. By
      introducing a double AGG to GGA mutation within this loop, its conformation is
      stabilised to form a new intra-molecular G:A:G base-triplet. The structure of the
      GGA mutant explains the relative instability of the wild-type loop. In a manner
      analogous to SL-3, we propose that conformational flexibility at this site may
      facilitate melting of the structure during Gag protein capture or genomic RNA
      dimerisation.

PMID- 12225749
TI  - The crystal structure of human cathepsin F and its implications for the
      development of novel immunomodulators.
AB  - Cathepsin F is a lysosomal cysteine protease of the papain family, and likely
      plays a regulatory role in processing the invariant chain that is associated with
      the major histocompatibility complex (MHC) class II. Evidence suggests that
      inhibiting cathepsin F activity will block MHC class II processing in
      macrophages. Consequently, inhibitors of this enzyme may be useful in treating
      certain diseases that involve an inappropriate or excessive immune response. We
      have determined the 1.7A structure of the mature domain of human cathepsin F
      associated with an irreversible vinyl sulfone inhibitor. This structure provides
      a basis for understanding cathepsin F's substrate specificity, and suggests ways
      of identifying potent and selective inhibitors of this enzyme.

PMID- 12225750
TI  - Specific mode of interaction between components of model pulmonary surfactants
      using computer simulations.
AB  - Atomistic molecular dynamics simulations and structural bioinformatics tools
      enable the identification of the exact mode of interaction between model
      pulmonary surfactant components. Two nanosecond long simulations of the N
      terminal region of human surfactant protein-B (SP-B(1-25)) in
      dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG)
      monolayers of different lipid surface densities reveal the preferential affinity
      of SP-B(1-25) for anionic phospholipids. In particular, arginine 12 and lysine 24
      interact strongly and with high specificity with the phosphate group of the DPPG
      lipids, stabilizing the position, the orientation, and the secondary structure of
      the peptide in the monolayer. The peptide lies at an oblique angle to the
      interfacial plane, ranging between 47 degrees and 62 degrees, increasing with
      decreasing lipid surface density. In DPPC monolayers the interaction is largely
      determined by hydrophobic interactions. The non-specific nature of DPPC-SP-B(1
      25) interactions allows for significant flexibility in the topology of the
      peptide in the lipid matrix. Bioinformatics tools are employed to generalize the
      simulation results to the sequences of SP-B(1-25) in other organisms. The
      importance of specific residues, and the role of the largely helical and
      amphiphilic nature of the peptide in the functionality of SP-B(1-25) are
      established. The synergy of classical mechanics tools with bioinformatics methods
      greatly enhances the molecular-level interpretation of pulmonary surfactant
      action and facilitates the development of design rules for synthetic surfactant
      analogues.

PMID- 12225751
TI  - Oligomerization of a peptide derived from the transmembrane region of the sodium
      pump gamma subunit: effect of the pathological mutation G41R.
AB  - The Na,K-ATPase, or sodium pump, is a ubiquitously expressed membrane-bound
      enzyme that controls the transmembrane (TM) gradients of sodium and potassium
      ions in animal cells. The enzyme comprises two subunits, alpha and beta, and in
      the kidney, is also associated with a small single-spanning membrane protein, the
      gamma subunit. This 65 amino acid residues protein has been linked to a form of
      dominant renal hypomagnesaemia resulting from substitution of a highly conserved
      glycine residue (Gly41) to arginine residue. In order to characterize the
      quaternary structure of the gamma subunit, and effects of the G41R mutation
      thereupon, we synthesized a series of peptides (wild-type and mutant) that span
      the gamma subunit TM region. Using circular dichroism spectroscopy, we show that
      the 32-amino acid residue peptides are random coils in aqueous buffer but
      spontaneously adopt an alpha-helical conformation in the presence of detergent
      micelles (sodium dodecyl sulfate, SDS, and perfluorooctanoate, PFO). Furthermore,
      fluorescence resonance energy transfer experiments, combined with polyacrylamide
      gel electrophoresis, demonstrate that while gamma-TM does not self-associate in
      SDS, it forms oligomers in PFO, a detergent that tolerates relatively weak
      associations between membrane proteins. Importantly, oligomerization of gamma-TM
      is abrogated in a peptide that contains either the disease-causing mutation G41R,
      or the more conservative mutation G41L. On the other hand, a peptide that
      contains a Gly-to-Arg substitution on a different face of the helix, at position
      35, retains its ability to oligomerize. Our results provide evidence for a link
      between renal hypomagnesaemia and gamma subunit oligomerization.

PMID- 12225752
TI  - Crystal structures of uninhibited factor VIIa link its cofactor and substrate
      assisted activation to specific interactions.
AB  - Factor VIIa initiates the extrinsic coagulation cascade; this event requires a
      delicately balanced regulation that is implemented on different levels, including
      a sophisticated multi-step activation mechanism of factor VII. Its central role
      in hemostasis and thrombosis makes factor VIIa a key target of pharmaceutical
      research. We succeeded, for the first time, in recombinantly producing N
      terminally truncated factor VII (rf7) in an Escherichia coli expression system by
      employing an oxidative, in vitro, folding protocol, which depends critically on
      the presence of ethylene glycol. Activated recombinant factor VIIa (rf7a) was
      crystallised in the presence of the reversible S1-site inhibitor benzamidine.
      Comparison of this 1.69A crystal structure with that of an inhibitor-free and
      sulphate-free, but isomorphous crystal form identified structural details of
      factor VIIa stimulation. The stabilisation of Asp189-Ser190 by benzamidine and
      the capping of the intermediate helix by a sulphate ion appear to be sufficient
      to mimic the disorder-order transition conferred by the cofactor tissue factor
      (TF) and the substrate factor X. Factor VIIa shares with the homologous factor
      IXa, but not factor Xa, a bell-shaped activity modulation dependent on ethylene
      glycol. The ethylene glycol-binding site of rf7a was identified in the vicinity
      of the 60 loop. Ethylene glycol binding induces a significant conformational
      rearrangement of the 60 loop. This region serves as a recognition site of the
      physiologic substrate, factor X, which is common to both factor VIIa and factor
      IXa. These results provide a mechanistic framework of substrate-assisted
      catalysis of both factor VIIa and factor IXa.

PMID- 12225753
TI  - Side-chain dynamics of the SAP SH2 domain correlate with a binding hot spot and a
      region with conformational plasticity.
AB  - X-linked lymphoproliferative disease is caused by mutations in the protein SAP,
      which consists almost entirely of a single SH2 domain. SAP interacts with the
      Tyr281 site of the T<-->B cell signaling protein SLAM via its SH2 domain.
      Interestingly, binding is not dependent on phosphorylation but does involve
      interactions with residues N-terminal to the Tyr. We have used 15N and 2H NMR
      relaxation experiments to investigate the motional properties of the SAP SH2
      domain backbone amides and side-chain methyl groups in the free protein and
      complexes with phosphorylated and non-phosphorylated peptides derived from the
      Tyr281 site of SLAM. The most mobile methyl groups are in side-chains with large
      RMSD values between the three crystal structures of SAP, suggesting that fast
      time-scale dynamics in side-chains is associated with conformational plasticity.
      The backbone amides of two residues which interact with the C-terminal part of
      the peptides experience fast time-scale motions in the free SH2 domain that are
      quenched upon binding of either the phosphorylated or non-phosphorylated peptide.
      Of most importance, the mobility of methyl groups in and around the binding site
      for residues in the N-terminus of the peptide is significantly restricted in the
      complexes, underscoring the dominance of this interaction with SAP and
      demonstrating a correlation between changes in rapid side-chain motion upon
      binding with local binding energy.

PMID- 12225754
TI  - Solution structure of a luteoviral P1-P2 frameshifting mRNA pseudoknot.
AB  - A hairpin-type messenger RNA pseudoknot from pea enation mosaic virus RNA1 (PEMV
      1) regulates the efficiency of programmed -1 ribosomal frameshifting. The
      solution structure and 15N relaxation rates reveal that the PEMV-1 pseudoknot is
      a compact-folded structure composed almost entirely of RNA triple helix. A three
      nucleotide reverse turn in loop 1 positions a protonated cytidine, C(10), in the
      correct orientation to form an A((n-1)).C(+).G-C(n) major groove base quadruple,
      like that found in the beet western yellows virus pseudoknot and the hepatitis
      delta virus ribozyme, despite distinct structural contexts. A novel loop 2-loop 1
      A.U Hoogsteen base-pair stacks on the C(10)(+).G(28) base-pair of the
      A(12).C(10)(+).G(28)-C(13) quadruple and forms a wedge between the pseudoknot
      stems stabilizing a bent and over-rotated global conformation. Substitution of
      key nucleotides that stabilize the unique conformation of the PEMV-1 pseudoknot
      greatly reduces ribosomal frameshifting efficacy.

PMID- 12225755
TI  - L22 ribosomal protein and effect of its mutation on ribosome resistance to
      erythromycin.
AB  - The ribosomal protein L22 is a core protein of the large ribosomal subunit
      interacting with all domains of the 23S rRNA. The triplet Met82-Lys83-Arg84
      deletion in L22 from Escherichia coli renders cells resistant to erythromycin
      which is known as an inhibitor of the nascent peptide chain elongation. The
      crystal structure of the Thermus thermophilus L22 mutant with equivalent triplet
      Leu82-Lys83-Arg84 deletion has been determined at 1.8A resolution. The
      superpositions of the mutant and the wild-type L22 structures within the 50S
      subunits from Haloarcula marismortui and Deinococcus radiodurans show that the
      mutant beta-hairpin is bent inward the ribosome tunnel modifying the shape of its
      narrowest part and affecting the interaction between L22 and 23S rRNA. 23S rRNA
      nucleotides of domain V participating in erythromycin binding are located on the
      opposite sides of the tunnel and are brought to those positions by the
      interaction of the 23S rRNA with the L22 beta-hairpin. The mutation in the L22
      beta-hairpin affects the orientation and distances between those nucleotides.
      This destabilizes the erythromycin-binding "pocket" formed by 23S rRNA
      nucleotides exposed at the tunnel surface. It seems that erythromycin, while
      still being able to interact with one side of the tunnel but not reaching the
      other, is therefore unable to block the polypeptide growth in the drug-resistant
      ribosome.

PMID- 12225756
TI  - The backbone conformational entropy of protein folding: experimental measures
      from atomic force microscopy.
AB  - The energy dissipated during the atomic force microscopy-based mechanical
      unfolding and extension of proteins is typically an order of magnitude greater
      than their folding free energy. The vast majority of the "excess" energy
      dissipated is thought to arise due to backbone conformational entropy losses as
      the solvated, random-coil unfolded state is stretched into an extended, low
      entropy conformation. We have investigated this hypothesis in light of recent
      measurements of the energy dissipated during the mechanical unfolding of
      "polyproteins" comprised of multiple, homogeneous domains. Given the assumption
      that backbone conformational entropy losses account for the vast majority of the
      energy dissipated (an assumption supported by numerous lines of experimental
      evidence), we estimate that approximately 19(+/-2)J/(mol K residue) of entropy is
      lost during the extension of three mechanically stable beta-sheet polyproteins.
      If, as suggested by measured peak-to-peak extension distances, pulling proceeds
      to near completion, this estimate corresponds to the absolute backbone
      conformational entropy of the unfolded state. As such, it is exceedingly close to
      previous theoretical and semi-empirical estimates that place this value at
      approximately 20J/(mol K residue). The estimated backbone conformational entropy
      lost during the extension of two helical polyproteins, which, in contrast to the
      mechanically stable beta-sheet polyproteins, rupture at very low applied forces,
      is three- to sixfold less. Either previous estimates of the backbone
      conformational entropy are significantly in error, or the reduced mechanical
      strength of the helical proteins leads to the rupture of a subsequent domain
      before full extension (and thus complete entropy loss) is achieved.

PMID- 12225757
TI  - Children's strategies in computational estimation.
AB  - We investigated strategies used to estimate answers to addition problems. Two
      hundred and sixteen participants (72 adults, 72 sixth graders, and 72 fourth
      graders) had to provide estimates of three-by-three digit addition problems
      (e.g., 249 + 743). The choice/no-choice method was used to obtain unbiased
      estimates of the performance characteristics of strategies. Results showed that
      (a) at all ages, the most common strategy was to round both operands down to the
      closest smaller decades, (b) strategy use and execution were influenced by
      participants' age, problem features, and relative strategy performance, and (c)
      age-related changes in computational estimation include changes in relative
      strategy use and execution, as well as in the relative influences of problem and
      strategy characteristics on strategy choices. Implications of these findings for
      understanding age-related differences in strategic aspects of computational
      estimation performance are discussed.

PMID- 12225758
TI  - Relating print and speech: the effects of letter names and word position on
      reading and spelling performance.
AB  - From an early age, children can go beyond rote memorization to form links between
      print and speech that are based on letter names in the initial positions of words
      (Treiman & Rodriguez, 1999; Treiman, Sotak, & Bowman, 2001). For example,
      children's knowledge of the name of the letter t helps them learn that the novel
      word TM is pronounced as team. Four experiments were carried out to determine
      whether letter names at the ends of words are equally useful. Four- and five-year
      olds derived little benefit from such information in reading (Experiments 1 and
      3) or spelling (Experiment 2), although adults did (Experiment 4). For young
      children, word-final information appears to have less influence on reading and
      spelling performance than does word-initial information. The results help
      delineate the circumstances under which children can go beyond a logographic
      approach in learning about print.

PMID- 12225759
TI  - Knowledge is not everything: analysis of children's performance on a haptic
      comparison task.
AB  - The relative effects of developmental level and domain-specific knowledge on
      children's ability to identify and make similarity decisions about object
      concepts based only on haptic (touch) information were investigated. Children
      aged 4-9 years with varying levels of dinosaur knowledge completed a cross
      comparison task in which they haptically explored pairs of familiar (dinosaur)
      and unfamiliar (sea creature) models that varied in terms of their degree of
      differentiability. Older children explored models more exhaustively, found more
      differentiating features and consequently made fewer errors than younger children
      did. High knowledge enabled children to identify models correctly, but was also
      associated with the use of a hypothesis testing strategy, which led children to
      make greater numbers of "miss" errors on the cross-comparison task. Performance
      in the control domain illustrated that the hypothesis testing strategy was
      specific to the high knowledge domain. Potential explanations for the role of
      knowledge and development in haptic exploration are considered.

PMID- 12225760
TI  - Parts and wholes in person recognition: developmental trends.
AB  - This study's aim is the investigation of short-term visual person recognition in
      8- and 10-year-olds and adults, within the part-whole paradigm introduced by.
      Natural unfamiliar whole persons were contrasted with natural unfamiliar faces to
      test for differences between person processing and face processing. Two
      experiments showed advantages of whole face recognition over isolated face
      feature recognition. Also, these was a complete over part probe advantage (CPA, )
      for person recognition in all age groups. Thus, recognition became more accurate
      between 8 years and adulthood, but no developmental shift in visual information
      processing was observable with face and whole person recognition. I conclude that
      person recognition does not rely on processes completely different from those of
      face recognition and that this holds for 8- and 10-year-olds as well as for
      adults.

PMID- 12225761
TI  - Cloning of zebrafish ovarian carbonyl reductase-like 20 beta-hydroxysteroid
      dehydrogenase and characterization of its spatial and temporal expression.
AB  - 20 beta-Hydroxysteroid dehydrogenase (20 beta-HSD) is a crucial enzyme that
      converts 17 alpha-hydroxyprogesterone to 17 alpha,20 beta-dihydroxy-4-pregnen-3
      one (DHP), which triggers oocyte maturation in most teleost fish. A full-length
      cDNA for a carbonyl reductase-like 20 beta-HSD (CR/20 beta-HSD) has been cloned
      from the zebrafish ovary. Although the zebrafish CR/20 beta-HSD is expressed in
      all of the tissues tested, it is predominantly expressed in the ovary, testis,
      kidney, and gill. In the ovary, the enzyme was shown to be expressed in the
      follicle cells and its expression appeared to be constitutive. No significant
      difference was noticed in the level of CR/20 beta-HSD expression among follicles
      of different stages. Furthermore, analysis of the ovarian samples taken at
      different times before spawning showed no significant change of the enzyme
      expression. In agreement with these results, treatment of the cultured zebrafish
      ovarian follicle cells with gonadotropin and activin had little effect on the
      expression of the enzyme. Taken together, these results point to the possibility
      that the gonadotropin-induced DHP production and final oocyte maturation in the
      zebrafish may not involve significant change of CR/20 beta-HSD expression as
      evidenced in the salmonids, or that there might be other isoforms of 20 beta-HSD
      whose expression is tightly controlled by endocrine and paracrine factors.

PMID- 12225762
TI  - Effects of simulated environmental conditions on glucocorticoid metabolite
      measurements in white-tailed deer feces.
AB  - Environmental conditions may influence fecal glucocorticoid metabolite
      measurements if feces cannot be collected immediately after deposition. To
      evaluate the influence of environmental conditions on fecal glucocorticoid
      metabolite concentrations, we exposed fresh fecal samples to 1 of 5 simulated
      conditions: (1) room temperature (22 degrees C), (2) high heat (38 degrees C),
      (3) alternating high heat and room temperature cycle, (4) alternating freezing (
      20 degrees C) and room temperature cycle, and (5) simulated rainfall (0.85 cm
      every other day at 22 degrees C) for 7 days. We collected fresh white-tailed deer
      (Odocoileus virginianus) feces at various times pre- and post-adrenocorticotropin
      injection to provide samples with initially low (n=5), medium (n=5), and high
      (n=5) glucocorticoid concentrations. Feces were mixed thoroughly and then
      allocated into five 10-g samples. Also, a 5-g sub-sample was taken from each
      fecal mass prior to treatment and stored at -20 degrees C until assayed. We
      subsampled from all treatments once every 24-h for 7 days. Fecal samples were
      assayed using [125I]corticosterone radioimmunoassay kits. Fecal glucocorticoid
      metabolites in all three groups in the simulated rainfall treatment and the low
      group in the alternating freezing and room temperature treatment increased
      significantly over the 7-day period. We believe increased microbial metabolism of
      fecal glucocorticoids may partly explain these results. Other biochemical
      processes (e.g., cleavage of conjugate side groups from hormone metabolites by
      non-microbial action or release of glucocorticoids from lipid micelles) may also
      have increased fecal glucocorticoid measurements. Our findings suggest that fecal
      samples exposed to rainfall for one week may artificially inflate fecal
      glucocorticoid measurements. Thus, researchers should recognize the potential
      bias when collecting fecal samples exposed to rainfall. Non-fresh samples may
      prove useful when care is taken to address the elevation in immunoreactive
      glucocorticoid concentrations.

PMID- 12225763
TI  - Effects of insulin-like growth factors (IGF-I and -II) on growth hormone and
      prolactin release and gene expression in euryhaline tilapia, Oreochromis
      mossambicus.
AB  - We investigated in vitro effects of insulin-like growth factors (IGF-I and -II)
      on growth hormone (GH) and prolactin (PRL) release and gene expression in
      euryhaline tilapia, Oreochromis mossambicus. Pituitaries were removed from
      freshwater-acclimated adult males and incubated for 2-24h in the presence of
      human IGF-I or -II at doses ranging from 1-1000 ng/ml (0.13-130 nM). IGF-I at
      concentrations higher than 10 ng/ml and IGF-II higher than 100 ng/ml
      significantly inhibited GH release after 8, 16, and 24h. No effect of IGFs was
      seen during the first 4h of incubation. IGFs at the same concentrations also
      significantly attenuated GH gene expression after 24h, although no effect was
      seen at 2h. By contrast, PRL(188) release was stimulated significantly and in a
      dose-related manner by IGF-I at concentrations higher than 10 ng/ml and by IGF-II
      at concentrations higher than 100 ng/ml within 2h. No stimulation was observed
      after 4h. Similarly, both IGFs at concentrations higher than 10 ng/ml increased
      PRL(177) release within 2h. However, no significant effect of IGF-I or -II was
      observed on mRNA levels of both PRLs after 2 and 24h at all concentrations
      examined. These results clearly indicate differential regulation of GH and PRL
      release and synthesis by IGFs in the tilapia pituitary, i.e., rapid-acting,
      stimulatory effects of IGFs on PRL release and slow-acting, inhibitory effects on
      GH release and synthesis.

PMID- 12225764
TI  - The Dmrt1 expression in sex-reversed gonads of amphibians.
AB  - Gonadal differentiation in amphibians is sensitive to steroids. The phenotypic
      sex can be changed by hormonal treatments, but the molecular mechanism for
      gonadal differentiation is not known. Up to date, many genes involved in gonadal
      differentiation have been isolated in vertebrates. Dmrt1, a gene that contains
      the DM-domain (Doublesex/Mab-3 DNA-binding motif), is considered to be one of the
      essential genes involved in the testicular differentiation cascade in mammals,
      birds, reptiles, and fish. However, this gene has not been isolated in amphibians
      yet. To elucidate its role(s) for gonadal differentiation in vertebrates, a
      molecular cloning of Dmrt1 in amphibians is urgent. In this study, we have
      successfully isolated a Dmrt1 homolog from the frog Rana rugosa testes cDNA
      library and examined its expression during gonadal differentiation and in sex
      reversed gonads. The Dmrt1 mRNA was exclusively detected in testis among adult
      tissues by the RT-PCR analysis. The Dmrt1 was first expressed in the
      differentiating testis at stage XXV in which spermatogonia are only germ cells,
      and became stronger at later stages. Moreover, the Dmrt1 transcript was not
      detected during ovarian differentiation. However, this gene was clearly expressed
      in XX sex-reversed gonads caused by injection of testosterone into all-female
      tadpoles that have well-differentiated ovaries. Taken together, the results
      suggest that Dmrt1 is closely implicated in testicular, but not ovarian
      differentiation in amphibians.

PMID- 12225765
TI  - FSH- and LH-cells originate as separate cell populations and at different
      embryonic stages in the chicken embryo.
AB  - The histological distribution of gonadotrophs containing either LH or FSH, but
      not both gonadotropins, has been demonstrated before in the juvenile and adult
      chicken throughout the caudal and cephalic anterior pituitary lobes. In the
      present investigation, the distribution of FSH- and/or LH-containing gonadotrophs
      was further investigated in the chicken embryo by use of the same homologous
      antibodies as used in our earlier study. Fluorescent dual-labeling
      immunohistochemistry revealed that during embryogenesis LH and FSH reside
      exclusively in separate gonadotrophs, as has been described before in the post
      hatch bird. LH-immunoreactive cells were observed for the first time at day 9 of
      embryogenesis. This is as much as 4 days earlier than the FSH-immunoreactive
      cells, which appeared at day 13 of embryogenesis. Our results confirm that FSH-
      and LH-containing gonadotrophs are distributed throughout both lobes of the
      anterior pituitary. No conspicuous differences were observed between the sexes in
      any of the aspects investigated. The described situation is unique in that it
      seems to imply the existence of separate cell lineages for FSH- and LH-producing
      cells, as opposed to the single gonadotrope lineage described in all other
      species studied so far, with the exception of bovine. Our data indeed raise the
      question as to which signaling and/or transcription factors may cause the unique
      dichotomy observed in the chicken gonadotrophs.

PMID- 12225766
TI  - The possible role of prolactin in laying performance and steroid hormone
      secretion in domestic hen (Gallus domesticus).
AB  - The aim of this study was to investigate the basic physiological mechanism
      involved in taking pauses between the sequences of egg laying in domestic hen to
      improve egg production by extending the sequence length and decreasing the
      intersequence pause days by modulating the prolactin concentration in birds.
      Fifty healthy female white leghorn birds were administered anti-prolactin agent
      (2-bromo-alpha-ergocriptine, Sigma, USA) subcutaneously at 100 microg/kg body
      weight at weekly intervals from 17th to 36th week of age. Another group of fifty
      birds was given placebo in place of the modulating agent. The level of prolactin
      remained lower in the treated birds than in the control birds throughout the
      production cycle up to 72 weeks of age. The level of prolactin in the control
      group was found to decrease during the peak production period. The average
      percentage of egg production from 19 to 72 week period was 87.67 in the treatment
      group as compared to 83.56 in the control group. Oestradiol-17beta and
      progesterone concentrations in the treated birds were significantly (P<0.01)
      higher than those in control birds, during and after withdrawal of the treatment.
      Prolactin level was negatively correlated with egg production (r=-0.02; r=-0.12)
      and with oestradiol-17beta (r=-0.75; r=-0.38) and progesterone (r=-0.20; r=
      0.83), respectively, in control and treatment groups. The total number of pause
      days during the production period decreased significantly (P<0.01) in the
      treatment group, resulting in a 4.11% increase in egg production. It is concluded
      that there is a consistent relationship between plasma prolactin in the
      physiological range and laying performance in domestic hen.

PMID- 12225767
TI  - Ontogenic origin of salmon GnRH neurons in the ventral telencephalon and the
      preoptic area in masu salmon.
AB  - During the ontogeny of masu salmon Oncorhynchus masou, neurons producing the
      salmon type of gonadotropin-releasing hormone (sGnRH) were first detected in the
      olfactory epithelium of the eyed egg and, subsequently, in the brain, suggesting
      a migration of these cells. Among sGnRH neurons distributed from the olfactory
      nerve (ON) through the preoptic area (POA), those in the ventral telencephalon
      (VT) and the POA are indicated to regulate gonadotropin secretion. Thus, it is of
      interest to know whether all the sGnRH neurons originate from the olfactory
      epithelium. In the present study, we examined by in situ hybridization whether
      sGnRH neurons are present in the VT-POA of fish, whose olfactory epithelia
      including sGnRH clusters were cauterized just after hatching (44 days after
      fertilization). Fish were sampled in June (212 days after the operation). Neurons
      expressing sGnRH mRNA were detected in the VT-POA as well as in the ON, ventral
      olfactory bulb, and transitional area between the olfactory bulb and
      telencephalon (which is considered to correspond to the terminal nerve ganglion)
      in the control group. In contrast, neurons expressing sGnRH mRNA were not
      detected in the VT-POA in the olfactory epithelium lesioned (OEL) group.
      Furthermore, pituitary sGnRH content in the OEL group was just above the
      detectable limit and was significantly lower than that in the corresponding
      control group in both sexes. These results indicate that sGnRH neurons in the VT
      POA are derived from the olfactory epithelium in masu salmon, although the
      possibility cannot be ruled out that sGnRH neurons in the VT-POA arise from the
      VT-POA, but were delayed in expressing sGnRH because of the trauma of
      cauterization.

PMID- 12225768
TI  - The vitellogenin cDNA of Cherax quadricarinatus encodes a lipoprotein with
      calcium binding ability, and its expression is induced following the removal of
      the androgenic gland in a sexually plastic system.
AB  - Oocyte maturation in decapod crustaceans is a two step process. Primary
      vitellogenesis is followed by a variable hiatus that lasts up to the onset of
      secondary vitellogenesis, which is marked by the rapid accumulation of yolk
      proteins in the oocytes. We have cloned a complete Cherax quadricarinatus
      vitellogenin cDNA. The sequenced cDNA contains a 2584 aa open reading frame which
      shows sequence similarity to vitellogenins from other crustaceans. The mRNA
      encodes at least two of the previously identified vitellin components, indicating
      that the primary translation product is subject to post-translational
      modification, including proteolytic cleavage. The region close to the 3(') end of
      the mRNA encodes a previously characterized negatively charged protein
      (provisionally designated P(106)). We show here that the negative charge of
      P(106) could be due to its ability to bind calcium. Northern blot data show that
      this gene is expressed as a single 8000 nt transcript and is present in the
      hepatopancreas of secondary-vitellogenic females. Primary vitellogenic and other
      tissues examined in male and female animals were negative. In sexually plastic
      intersex animals, removal of the androgenic gland results in vitellogenin
      transcription, indicating that the gene is negatively regulated by the androgenic
      gland.

PMID- 12225769
TI  - Effects of functional peripheral sympathetic denervation induced by guanethidine
      on follicular development and ovulation of the adult female guinea pig.
AB  - The present study investigates the effects of functional sympathetic peripheral
      denervation induced by guanethidine sulphate (GTD) to adult female guinea pigs in
      the follicular (FPh) or luteal phases (LPh) on their oestrous cyclicity and
      ovulation. No differences were observed in oestrous cyclicity or the average
      number of corpora lutea present in the ovaries between the control and denervated
      animals. Guanethidine sulphate administration resulted in a significant decrease
      in ovarian norepinephrine content, higher for the left ovary than for the right
      one. Serum oestrogen and progesterone concentrations, the mean of follicles, and
      its diameter were different, depending on the oestral cycle in which the
      treatment was performed. These results suggest that in adult normal female guinea
      pigs, ovarian innervation participates in the regulation of follicular
      development in an inhibitory way.

PMID- 12225770
TI  - Effects of guanethidine administration on compensatory ovarian hypertrophy,
      compensatory ovulation and follicular development in the prepubertal female
      guinea pig.
AB  - We analyzed the participation of sympathetic ovarian innervation in the
      prepubertal female guinea pig on regulation of compensatory ovarian hypertrophy
      (COH) and compensatory ovulation at puberty. The COH of the left ovary was
      significantly higher that of the right one (left ovary: 41.5+/-5.2 vs. 27.5+/
      5.6%, p<0.05, Kruskal-Wallis test). The sympathetic denervation induced by
      guanethidine administration beginnings at birth or on day 10 resulted in a
      significant increase of the COH by each ovary (p<0.05, Kruskal-Wallis test). Only
      one of the six untreated control guinea pigs sacrificed at the follicular phase
      ovulate. All the hemiovariectomized animals with the left ovary in situ ovulated,
      while only two out of five with the right ovary in situ did (100 vs. 40%:
      p<0.001, Kruskal-Wallis test), unlike the denervated animals, which did not
      ovulate. The number of corpora lutea present in the ovaries was similar among all
      groups of animals. These results demonstrate differences in the follicular
      diameter in untreated female guinea pigs and add further support to the concept
      of asymmetrical response of the ovaries to denervation.

PMID- 12225771
TI  - Activation of the growth hormone/insulin-like growth factor axis by treatment
      with 17 alpha-methyltestosterone and seawater rearing in the tilapia, Oreochromis
      mossambicus.
AB  - Effects of 17 alpha-methyltestosterone (MT) treatment and environmental salinity
      on the growth hormone (GH)/insulin-like growth factor (IGF) axis were examined in
      the euryhaline tilapia, Oreochromis mossambicus. Yolk-sac fry were collected from
      brood stock in fresh water (FW). After yolk-sac absorption, they were assigned
      randomly to 1 of 4 groups: FW, MT treatment in FW, SW, and MT treatment in
      seawater (SW). After 147 days, FW controls had the lowest levels of GH mRNA
      followed by FW fish treated with MT and SW control fish. Seawater fish fed with a
      diet containing MT, which grew the fastest, had significantly higher levels of GH
      mRNA than all the other groups. A significant correlation was observed between GH
      mRNA and the size of the individual fish. By contrast, plasma GH levels did not
      vary significantly among the groups. Pituitary GH mRNA levels, plasma IGF-I
      levels, and fish size varied in a correlated pattern, i.e., SW+MT>FW+MT=SW
      control>FW control. The tilapia pituitary produces two prolactins (PRLs),
      PRL(177) and PRL(188). Prolactin(177), but not PRL(188), exhibits growth
      promoting actions in FW tilapia. Pituitary mRNA levels of both PRLs were
      significantly higher in fish reared in FW than those reared in SW. Treatment with
      MT significantly increased mRNA levels of both PRLs in FW, but had no effect on
      SW fish. No correlation was seen between plasma PRL levels and growth or between
      PRL mRNA levels and growth. These results indicate that SW rearing and MT
      treatment stimulate the GH/IGF-I axis, and suggest that pituitary GH mRNA at this
      stage of development is a better indicator of growth than plasma levels of GH and
      IGF-I.

PMID- 12225772
TI  - Hyper- or hypothyroidism: its association with the development of ascites
      syndrome in fast-growing chickens.
AB  - The ascites syndrome in broiler chickens is attributed to the progress in genetic
      selection for rapid growth, coupled with the metabolic burden imposed by exposure
      to a relatively low-ambient temperature (T(a)). The syndrome is mainly
      characterized by hematocrit elevation, decline in blood oxygen saturation,
      accumulation of fluid in the abdominal cavity, and finally, death. Ascitic
      chickens have demonstrated hypothyroidism coupled with a marked stress response
      (high corticosterone concentration) and reduction in the hemoglobin content. The
      objective of the present study was to examine the role of thyroid and
      corticosterone hormones in the development of the syndrome. Ascites was induced
      by exposure to a gradually declining T(a) and supplementation of a pellet-form
      diet. Exogenous thyroxin (T(4)) and propylthiouracil (PTU) (in Experiments 1 and
      2, respectively) were supplemented in drinking water to induce hyper- or
      hypothyroidism, respectively. Ascites syndrome was developed in 21.5% and 23% of
      the birds exposed to ascites-induced conditions (Exps. 1 and 2, respectively).
      Excess T(4) (Exp. 1) significantly reduced the percentage of ascites (down to
      7%), whereas PTU (Exp. 2) significantly increased the appearance of the syndrome
      (35%). In the T(4)-treated chickens, although the T(4) concentration reached
      pharmacological levels, the triiodothyronine (T(3)) concentration remained within
      physiological levels, whereas T(3) in the ascitic birds exhibited a reduction
      pattern similar to that observed in the ascitic non-supplemented ones. In the PTU
      treated chickens, however, both ascitic and non-ascitic birds demonstrated
      significant reductions in both T(4) and T(3) concentrations. In both experiments,
      ascitic chickens exhibited a considerable stress response, characterized by a
      significant and persisted elevation in plasma corticosterone concentration, which
      was in accordance with a similar elevation of hematocrit, and the PTU-treated non
      ascitic birds exhibited a similar stress response. At 5 weeks of age, ascitic
      birds and the PTU-treated non-ascitic ones exhibited significant reductions in
      the hemoglobin content of their red blood cells. It may be concluded that
      deficiency in the thyroid hormones and elevated corticosterone may play a key
      deleterious role in the development of the ascites syndrome.

PMID- 12225773
TI  - Cloning and characterisation of the GH gene from the common dolphin (Delphinus
      delphis).
AB  - The sequence of growth hormone (GH) is generally strongly conserved in mammals,
      but episodes of rapid change occurred during the evolution of primates and
      artiodactyls, when the rate of GH evolution apparently increased at least 50
      fold. As a result, the sequences of human and ruminant GHs differ substantially
      from those of other non-primate GHs. Recent molecular studies have suggested that
      cetaceans are closely related to artiodactyls and may be deeply nested within the
      artiodactyl phylogenetic tree. To extend the knowledge of GH in Cetartiodactyla
      (Artiodactyla plus Cetacea), we have cloned and characterised a single GH gene
      from the common dolphin (Delphinus delphis), using genomic DNA and a polymerase
      chain reaction technique. As in other mammals, the dolphin GH gene comprises five
      exons and four introns. The deduced sequence for the mature dolphin GH differs
      from that of pig at two residues only, showing that the apparent burst of rapid
      evolution of GH occurred largely after the separation of cetaceans and ruminants.

PMID- 12225774
TI  - Characterization of transactivation domain and developmental expression of
      pituitary specific transcription factor, Pit-1 of ayu (Plecoglossus altivelis).
AB  - Pit-1 is a pituitary-specific transcription factor, which regulates the
      expression of growth hormone, prolactin, and thyroid stimulating hormone-beta
      genes. We previously reported the expression of a Pit-1 gene from ayu
      (Plecoglossus altivelis), which is an important cultivated food fish in Taiwan
      and Japan. Comparison of ayu Pit-1 with that of salmon, turkey, and rodent,
      revealed that the Pit-1 structure is highly conserved through vertebrates,
      especially in POU-specific and POU-homeo domains. The variation among fish, bird,
      and mammal are mainly found in transactivation domain by alternative splicing and
      initiation. Three insertions were found. The gamma-insert in fish Pit-1 is
      homologous to the exon 2a of avian Pit-1, which is not found in mammals. The beta
      insert of fish Pit-1 is homologous to the 28 amino acids (a.a.) and 26 a.a.
      insert of avian Pit-1 beta(*) and mammalian Pit-1 beta, respectively. An
      additional similarity was noticed between fish and bird, as both of them contain
      7 a.a. insert that is not present in mammalian Pit-1. By site directed
      mutagenesis, we demonstrated that the beta, gamma, and the 7 a.a. inserts of ayu
      Pit-1 are critical for activation of zebrafish growth hormone promoter. The ayu
      Pit-1 protein was found to be expressed specifically in pituitary gland, and its
      mRNA was first detected at embryonic day 4, significantly increased at embryonic
      day 5, then sustained to time of hatching at day 8.

PMID- 12225775
TI  - Observing structure, function and assembly of single proteins by AFM.
AB  - Single molecule experiments provide insight into the individuality of biological
      macromolecules, their unique function, reaction pathways, trajectories and
      molecular interactions. The exceptional signal-to-noise ratio of the atomic force
      microscope allows individual proteins to be imaged under physiologically relevant
      conditions at a lateral resolution of 0.5-1nm and a vertical resolution of 0.1
      0.2nm. Recently, it has become possible to observe single molecule events using
      this technique. This capability is reviewed on various water-soluble and membrane
      proteins. Examples of the observation of function, variability, and assembly of
      single proteins are discussed. Statistical analysis is important to extend
      conclusions derived from single molecule experiments to protein species. Such
      approaches allow the classification of protein conformations and movements.
      Recent developments of probe microscopy techniques allow simultaneous measurement
      of multiple signals on individual macromolecules, and greatly extend the range of
      experiments possible for probing biological systems at the molecular level.
      Biologists exploring molecular mechanisms will benefit from a burgeoning of
      scanning probe microscopes and of their future combination with molecular
      biological experiments.

PMID- 12225776
TI  - Interactions between dihydropyridine receptors and ryanodine receptors in
      striated muscle.
AB  - Excitation-contraction coupling in both skeletal and cardiac muscle depends on
      structural and functional interactions between the voltage-sensing
      dihydropyridine receptor L-type Ca(2+) channels in the surface/transverse tubular
      membrane and ryanodine receptor Ca(2+) release channels in the sarcoplasmic
      reticulum membrane. The channels are targeted to either side of a narrow
      junctional gap that separates the external and internal membrane systems and are
      arranged so that bi-directional structural and functional coupling can occur
      between the proteins. There is strong evidence for a physical interaction between
      the two types of channel protein in skeletal muscle. This evidence is derived
      from studies of excitation-contraction coupling in intact myocytes and from
      experiments in isolated systems where fragments of the dihydropyridine receptor
      can bind to the ryanodine receptors in sarcoplasmic reticulum vesicles or in
      lipid bilayers and alter channel activity. Although micro-regions that
      participate in the functional interactions have been identified in each protein,
      the role of these regions and the molecular nature of the protein-protein
      interaction remain unknown. The trigger for Ca(2+) release through ryanodine
      receptors in cardiac muscle is a Ca(2+) influx through the L-type Ca(2+) channel.
      The Ca(2+) entering through the surface membrane Ca(2+) channels flows directly
      onto underlying ryanodine receptors and activates the channels. This was thought
      to be a relatively simple system compared with that in skeletal muscle. However,
      complexities are emerging and evidence has now been obtained for a bi-directional
      physical coupling between the proteins in cardiac as well as skeletal muscle. The
      molecular nature of this coupling remains to be elucidated.

PMID- 12225777
TI  - Molecular evolution before the origin of species.
AB  - Amino acids at conserved sites in the residue sequence of 10 ancient proteins,
      from 844 phylogenetically diverse sources, were used to specify their time of
      origin in the interval before species divergence from the last common ancestor
      (LCA). The order of amino acid addition to the genetic code, based on
      biosynthesis path length and other molecular evidence, provided a reference for
      evaluating the 'code age' of each residue profile examined. Significantly earlier
      estimates were obtained for conserved amino acid residues in these proteins than
      non-conserved residues. Evidence from the primary structure of 'fossil' proteins
      thus corroborated the biosynthetic order of amino acid addition to the code.Low
      potential ferredoxin (Fdxn) had the earliest residue profile among the proteins
      in this study. A phylogenetic tree for 82 prokaryote Fdxn sequences was rooted
      midway between bacteria and archaea branches. LCA Fdxn had a 23-residue
      antecedent whose residue profile matched mid-expansion phase codon assignments
      and included an amide residue. It contained a highly acidic N-terminal region and
      a non-charged C-terminal region, with all four cysteine residues. This small
      protein apparently anchored a [4Fe-4S] cluster, ligated by C-terminal cysteines,
      to a positively charged mineral surface, consistent with mediating e(-) transfer
      in a primordial surface system before cells appeared. Its negatively charged N
      terminal 'attachment site' was highly mutable during evolution of ancestral Fdxn
      for Bacteria and Archaea, consistent with a loss of function after cell
      formation. An initial glutamate to lysine substitution may link 'attachment site'
      removal to early post-expansion phase entry of basic amino acids to the code. As
      proteins evidently anchored non-charged amide residues initially, surface
      attachment of cofactors and other functional groups emerges as a general function
      of pre-cell proteins.A phylogenetic tree of 107 proteolipid (PL) helix-1
      sequences from H(+)-ATPase of bacteria, archaea and eukaryotes had its root
      between prokaryote branches. LCA PL h1 residue profile optimally fit a late
      expansion phase codon array. Sequence repeats in transmembrane PL helices h1 and
      h2 indicated formation of the archetypal PL hairpin structure involved successive
      tandem duplications, initiated within the gene for an 11-residue (or 4-residue)
      hydrophobic peptide. Ancestral PL h1 lacked acidic residues, in a fundamental
      departure from the prototype pre-cell protein. By this stage, proteins with a
      hydrophobic domain had evolved. Its non-polar, late expansion phase residue
      profile point to ancestral PL being a component of an early permeable cell
      membrane. Other indicators of cell formation about this stage of code evolution
      include phospholipid biosynthesis path length, FtsZ residue profile, and late
      entry of basic amino acids into the genetic code. Estimates based on conserved
      residues in prokaryote cell septation protein, FtsZ, and proteins involved with
      synthesis, transcription and replication of DNA revealed FtsZ, ribonucleotide
      reductase, RNA polymerase core subunits and 5'-->3' flap exonuclease, FEN-1,
      originated soon after cells putatively evolved. While reverse transcriptase and
      topoisomerase I, Topo I, appeared late in the pre-divergence era, when the
      genetic code was essentially complete. The transition from RNA genes to a DNA
      genome seemingly proceeded via formation of a DNA-RNA heteroduplex. These results
      suggest formation of DNA awaited evolution of a catalyst with a hydrophobic
      domain, capable of sequestering radical bearing intermediates in its synthesis
      from ribonucleotide precursors. Late formation of topology altering protein, Topo
      I, further suggests consolidation of genes into chromosomes followed synthesis of
      comparatively thermostable DNA strands.

PMID- 12225778
TI  - Life after LIFE. Cardiovascular benefits of angiotensin II receptor blockade in
      older people with essential hypertension, left ventricular hypertrophy and
      diabetes mellitus.

PMID- 12225779
TI  - Cytokines and anti-cytokine therapeutic approaches to chronic heart failure.
AB  - Recent investigations have shown that, in addition to neurohormonal system
      overactivation, another class of biologically active molecules, termed cytokines,
      is also overexpressed in the setting of chronic heart failure and participates
      actively in the progression of the syndrome. In this article, we present recent
      experimental and clinical data describing the pathophysiological role of
      cytokines in left ventricular remodeling, endothelial dysfunction, and peripheral
      myopathy characterizing the progression of chronic heart failure, as well as
      novel therapeutic approaches aimed at attenuating the deleterious effects of
      cytokines on the cardiovascular system.

PMID- 12225780
TI  - Microchimerism and autoimmune diseases.
AB  - Microchimerism is defined by the presence within an individual of a low level of
      cells derived from another individual. Systemic sclerosis is clinically similar
      to chronic graft-versus-host disease, a known condition of chimerism, which has
      led some authors to explore the hypothesis that microchimerism may contribute to
      the pathogenesis of systemic sclerosis and other autoimmune disorders. This
      article reviews early studies that lend support to this hypothesis.

PMID- 12225781
TI  - Hypertension is frequently present in patients with reflux esophagitis or
      Barrett's esophagus but not in those with non-ulcer dyspepsia.
AB  - BACKGROUND: Elevated mortality due to cardiovascular disease has been reported
      for patients with Barrett's esophagus (BE). We compared the prevalence of risk
      factors for cardiovascular disease in patients with BE, reflux esophagitis (RE),
      and non-ulcer dyspepsia (NUD) with that of the general population. METHODS:
      Patients with upper gastrointestinal complaints and BE, RE, or NUD were compared
      with a matched cohort from the general population using a questionnaire and blood
      pressure and cholesterol measurements. RESULTS: Hypertension occurred more
      frequently in patients with BE (odds ratio 5.1, P<0.0001) and RE (odds ratio 3.8,
      P<0.001), but not in those with NUD. Serum total cholesterol was higher in BE
      (P=0.02) and borderline in RE (P=0.06) but not in NUD. Mean HDL cholesterol
      levels, body mass index, and smoking did not differ. CONCLUSIONS: This study
      suggests that BE and RE found at diagnostic endoscopy are associated with an
      increased prevalence of hypertension and a higher total cholesterol level than in
      the general population. If so, this would explain the increased mortality during
      the follow-up of BE patients, and it should be taken into account when designing
      or evaluating follow-up studies of BE.

PMID- 12225782
TI  - Helicobacter pylori infection in diabetic patients: prevalence and endoscopic
      findings.
AB  - BACKGROUND: In patients with diabetes mellitus, chronic infections are frequent
      and severe, due to the impairment of their immune status. However, data on the
      prevalence of Helicobacter pylori (H. pylori) infection in diabetics are scanty
      and contradictory. The aim of our study was to assess the prevalence of H. pylori
      infection in diabetic patients and to evaluate the association between endoscopic
      features and H. pylori colonization of the gastric mucosa in diabetes mellitus.
      METHODS: A cross-sectional study of 172 dyspeptic patients (67 diabetics and 105
      nondiabetic subjects) was designed. In all cases, an upper gastrointestinal
      endoscopy was performed, gastroduodenal lesions were noted, and the presence of
      gastritis and H. pylori was assessed by histopathological examination.
      Differences between diabetic patients and nondiabetic subjects were evaluated.
      RESULTS: The difference of H. pylori prevalence between diabetics (37.3%) and
      nondiabetics (35.2%) was not significant (P=0.78). Nor did the prevalence of
      gastritis and peptic ulcer differ significantly between the two groups (59.7% vs.
      49.5%, P=0.19; and 32.8% vs. 40.9%, P=0.08, respectively). Studying only H.
      pylori-positive patients, we found no difference between diabetics and
      nondiabetics with regard to the prevalence of either gastritis (80% vs. 72.9%,
      P=0.71) or peptic ulcer (91.8% vs. 76%, P=0.09). CONCLUSIONS: Our data do not
      support an association between H. pylori infection and diabetes mellitus. This is
      confirmed by the lack of difference between diabetics and nondiabetics with
      regard to the prevalence of both H. pylori infection and H. pylori-related
      gastroduodenal disorders.

PMID- 12225783
TI  - Unnecessary peripheral intravenous catheterisation on an acute medical admissions
      unit: a preliminary study.
AB  - BACKGROUND: The ability to secure peripheral intravenous access is regarded as a
      basic medical skill that is often required for the management of patients
      admitted to acute medical admission wards. The decision to insert a peripheral
      intravenous catheter (PIC) is usually taken by relatively inexperienced members
      of the acute medical team and is primarily based on 'traditional' or 'routine'
      practice, rather than on an assessment of need. Furthermore, there appears to be
      little recognition of the potentially serious adverse events associated with PIC
      insertion. METHOD: We conducted a prospective study to evaluate unnecessary PIC
      insertion in a United Kingdom teaching hospital's acute medical admissions unit.
      RESULTS: Of the 338 patients included in the study, 272 (80.5%) received a PIC.
      Of these, 179 patients (66%) received a PIC that had been used by the post-on
      call ward round. Of the 93 patients (34%) with an unused PIC, 30 patients (11%)
      had been catheterised inappropriately by the study criteria. CONCLUSIONS: Despite
      our use of conservative criteria for PIC insertion, a notable level of
      inappropriate peripheral intravenous catheterisation was identified. A
      hypothetical cost-minimisation analysis is presented and a care pathway for best
      practice proposed.

PMID- 12225784
TI  - Pulmonary function abnormalities in respiratory asymptomatic patients with
      inflammatory bowel disease.
AB  - BACKGROUND: There is evidence that pulmonary function abnormalities are present
      in patients with inflammatory bowel disease (IBD). The aim of this crossover
      study was to assess the frequency of pulmonary dysfunction in patients with IBD
      and to define the importance of possible confounding factors. METHODS: We
      investigated a total of 44 patients with Crohn's disease or ulcerative colitis
      and no pulmonary symptoms or a history of respiratory diseases by means of
      pulmonary function testing and chest X-ray. As controls we examined 44 healthy
      subjects matched for gender, age, and smoking status. RESULTS: A total of 21% of
      the subjects with ulcerative colitis and 20% with Crohn's disease showed an
      obstructive and/or restrictive ventilatory defect. Pulmonary function
      abnormalities were significantly more frequent in patients with IBD than in the
      controls (5%, P<0.05). There was no correlation between pulmonary function
      abnormalities and site, activity, or duration of bowel disease, current
      medication, smoking habits, or history of atopy. CONCLUSIONS: Pulmonary
      involvement seems to be a more frequent extraintestinal manifestation of IBD than
      thus far supposed. The causes or confounding factors are uncertain.

PMID- 12225785
TI  - Successful treatment of fulminant pneumococcal sepsis with recombinant tissue
      plasminogen activator.
AB  - This case report describes a patient with a rapidly progressive pneumococcal
      septic shock and purpura fulminans. Despite maximal conventional treatment, the
      patient developed progressive multiple organ failure with imminent necrosis of
      the extremities. This extremely rare, but often fatal, disease responded
      dramatically to the infusion of recombinant tissue plasminogen activator.

PMID- 12225786
TI  - Retroperitoneal fibrosis and p-ANCA-associated polyarteritis nodosa: coincidental
      or common etiology?
AB  - We describe a 65-year-old female patient who presented with idiopathic
      retroperitoneal fibrosis and polyarteritis nodosa. In addition, antineutrophil
      cytoplasmatic antibodies were found with specificity for myeloperoxidase (p-ANCA;
      anti-MPO). Following immunosuppressive treatment, regression of signs and
      symptoms was observed, together with the disappearance of these specific
      antimyeloperoxidase antibodies. These findings, combined with data available in
      the literature, suggest a common pathogenesis of both disorders, possibly
      involving antineutrophil cytoplasmatic antibodies.

PMID- 12225787
TI  - An unusual case of gastric outlet obstruction.

PMID- 12225788
TI  - Current understanding of stem cell mobilization: the roles of chemokines,
      proteolytic enzymes, adhesion molecules, cytokines, and stromal cells.
AB  - Mobilization of hematopoietic stem and progenitor cells from the bone marrow into
      the circulation by repetitive, daily stimulations with G-CSF alone, or in
      combination with cyclophosphamide, is increasingly used clinically; however, the
      mechanism is not fully understood. Moreover, following mobilization stem cells
      also home back to the bone marrow, suggesting that stem cell release/mobilization
      and homing are sequential events with physiological roles. Previously, a role for
      cytokines such as G-CSF and SCF, and adhesion molecules such as VLA-4 and P/E
      selectins, was determined for stem cell mobilization. Recent results using
      experimental animal models and samples from clinical mobilization protocols
      demonstrate major involvement of chemokines such as stromal derived factor-1 (SDF
      1) and IL-8, as well as proteolytic enzymes such as elastase, cathepsin G, and
      various MMPs in the mobilization process. These results will be reviewed together
      with the central roles of SDF-1 and CXCR4 interactions in G-CSF or G-CSF in
      combination with cyclophosphamide-induced mobilization. Furthermore, the central
      role of this chemokine in stem cell homing to the bone marrow as well as
      retention of undifferentiated cells within this tissue will also be discussed.

PMID- 12225789
TI  - In situ activation of caspases and serine proteases during apoptosis detected by
      affinity labeling their enzyme active centers with fluorochrome-tagged
      inhibitors.
AB  - Activation of caspases is the key event of apoptosis. To detect this event in
      situ we applied fluorochrome-labeled inhibitors of caspases (FLICA) as affinity
      labels of active centers of these enzymes. The FLICA are fluorescein- or
      sulforhodamine-conjugated peptide-fluoromethyl ketones that covalently, with 1:1
      stoichiometry, bind to enzymatic centers of caspases; the specificity is provided
      by the peptide sequence of amino acids. Similarly, we applied fluorescent
      inhibitors of serine proteases (FLISP) to detect active sites of the latter
      enzymes. Exposure of live cells to FLICA of FLISP led to uptake of these ligands
      and their binding to activated caspases or active sites of serine proteases; the
      unbound reagents were removed by cell rinse. Only cells undergoing apoptosis were
      labeled with FLISP or FLICA. Intracellular binding sites of FLICA are consistent
      with known localization of caspases. Covalent binding of FLICA or FLISP allowed
      us to identify the labeled proteins by immunoblotting: the proteins that bound
      individual FLICAs had molecular weight between 17 and 22 kDa, which corresponds
      to large subunits of the caspases; two proteins reacting with FLISP were about 57
      and 60 kDa, which suggests that they are novel enzymes. Detection of caspases or
      serine proteases activation can be combined with other markers of apoptosis or
      cell cycle for multiparametric analysis by flow or laser scanning cytometry.
      Being caspase inhibitors, FLICA arrest the process of apoptosis and prevent cell
      disintegration. The stathmo-apoptotic assay was developed, therefore, to obtain
      cumulative apoptotic index over a long period of time and estimate a rate of cell
      entry into apoptosis for cell populations.

PMID- 12225790
TI  - Activation of phosphatidylinositol 3-kinase is important for erythropoietin
      induced erythropoiesis from CD34(+) hematopoietic progenitor cells.
AB  - OBJECTIVE: Several transducing molecules, including JAK2, STAT5, MAP kinases,
      phosphatidylinositol 3-kinase (PI3K), phospholipase C-gamma1, and PKC are
      activated by interaction between erythropoietin (EPO) and the EPO receptor. The
      aim of this was to examine the relative involvement of PI3K in the development of
      glycophorin A (GPA)(+) erythroid cells from normal hematopoietic progenitor
      cells. MATERIALS AND METHODS: CD34(+) hematopoietic progenitor cells or
      subpopulations obtained by FACS sorting were cultured in serum-free medium
      containing EPO with or without inhibitors for PI3K, p38, MEK, or PKC for various
      time periods before phenotypic analysis or detection of apoptosis by flow
      cytometry, cell cycle analysis, high-resolution tracking of cell division,
      Western blot analysis, or Akt kinase assay were performed. RESULTS: The PI3K
      inhibitor LY294002 completely counteracted the EPO-induced proliferation of
      CD34(+) progenitor cells and CD34(+)CD71(+)CD45RA(-) erythroid progenitors.
      LY294002 also highly suppressed the expanded erythropoiesis induced by the
      combined action of EPO and stem cell factor. The profound inhibitory effect of
      LY294002 on proliferation was caused by its induction of cell cycle arrest in the
      G(0)/G(1) phase of the cell cycle. Some cells acquired GPA expression before they
      went through cell division. This was completely blocked by LY294002, implying an
      inhibitory effect on maturation. In addition, LY294002 completely blocked the
      viability-enhancing effect of EPO in CD34(+)CD71(+)CD45RA(-) erythroid
      progenitors. LY294002 and various inhibitors of PKC completely suppressed the EPO
      induced increase in the activity of Akt kinase, a direct downstream target of
      PI3K. CONCLUSIONS: Our results point to an important role for PI3K in mediating
      EPO-induced survival, proliferation, and possibly maturation of early erythroid
      progenitors.

PMID- 12225791
TI  - Vasoactive intestinal peptide (VIP) inhibits the proliferation of bone marrow
      progenitors through the VPAC1 receptor.
AB  - OBJECTIVE: The cellular and molecular mechanisms of hematopoietic stimulation
      have been studied. However, an understanding of negative effects in the
      hematopoietic system remains elusive. To this end, we studied the effects of
      vasoactive intestinal peptide (VIP) on bone marrow (BM) progenitors. MATERIALS
      AND METHODS: Different BM cell subsets were used to perform clonogenic assay for
      granulocytic (CFU-GM) or erythroid (BFU-E and CFU-E) progenitors with 10(-7)-10(
      13) M VIP. The relevant receptor was verified with specific antagonists, or
      agonists, semi-quantitative RT-PCR, and chemical cross-linking studies with
      stromal membranes. RESULTS: Assays performed with unfractionated mononuclear
      cells and enriched CD34(+) cells showed dose-dependent inhibition on BM
      progenitors with significant inhibition up to 10(-10) M. Nylon wool separated
      cells, which depleted stroma, reversed the inhibitory effects of VIP between 10
      and 20%. Combined experimental evaluation indicated that the effects of VIP on BM
      functions are mediated through the type 1 receptor (VPAC1). VIP induced the
      production of TGF-beta and TNF-alpha in BM mononuclear cells and stroma. These
      cytokines are partly involved in reversing the suppressive effects of VIP on CFU
      GM. CONCLUSIONS: The effect of VIP on BM progenitors could be mediated through
      direct and indirect mechanism. Direct effects were evident by the suppressive
      effects of VIP on clonogenic assays with highly purified CD34(+) cells. Indirect
      effects were mediated through putative functions of the stromal cells and the
      production of TGF-beta and TNF-alpha.

PMID- 12225792
TI  - Roles of spleen and liver in development of the murine hematopoietic system.
AB  - OBJECTIVE: Hematopoietic stem cells (HSCs) and colony-forming progenitor cells
      (CFCs) are believed to migrate from liver to bone marrow (BM) around the time of
      birth, where they remain throughout the animal's life. Although in mice the
      spleen is also a hematopoietic organ, neither the origin nor the contribution of
      spleen HSCs to hematopoietic homeostasis has been assessed relative to that of BM
      HSCs. To investigate these issues we quantitated CFC and HSC activity in the
      spleen, BM, peripheral blood, and liver of the mouse during ontogeny. METHODS:
      CFCs were assessed by clonogenic colony formation, and HSCs by long-term
      reconstituting ability. RESULTS: CFCs gradually increased in the BM and decreased
      in the liver with age. Increased prevalence of CFCs in fetal and pup blood
      occurred at day (d) 12 postcoitus (pc) and during the period of d16 pc to 4d
      postbirth, corresponding to the times when hematopoietic cells migrate from the
      yolk sac and/or aorta-gonad-mesonephros (AGM) to the fetal liver and from the
      neonatal liver to the BM, respectively. In the spleen, CFCs displayed two peaks
      of activity at 2d and 14d-15d postbirth. Spleen HSCs also fluctuated during this
      time period. Neonatal splenectomy did not alter CFC or HSC frequencies in the BM,
      but CFCs increased in the livers of splenectomized mice. CONCLUSIONS: These data
      demonstrate that the liver may act as a site of extramedullary hematopoiesis in
      the neonate, especially in the absence of the spleen, and imply that the spleen,
      BM, and liver cooperatively contribute to hematopoietic homeostasis.

PMID- 12225794
TI  - Receptor for hyaluronan acid-mediated motility (RHAMM) is a new immunogenic
      leukemia-associated antigen in acute and chronic myeloid leukemia.
AB  - OBJECTIVE: Identification of leukemia-associated antigens (LAA) eliciting an
      immune response in patients is a prerequisite for specific immunotherapy of
      leukemias. To identify new LAA, we used the method of serologic screening of cDNA
      expression libraries (SEREX). MATERIALS AND METHODS: A SEREX library of the cell
      line K562 was subjected to allogeneic screening with sera from patients with
      acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) vs sera from
      healthy volunteers. RESULTS: The receptor for hyaluronan acid-mediated motility
      (RHAMM) involved in cell growth and metastasis was identified as a new LAA.
      Serologic responses to RHAMM were observed in patients with AML (42%), CML (31%),
      melanoma (83%), renal cell carcinoma (40%), breast cancer (67%), and ovarian
      carcinoma (50%), but not in HV or patients with autoimmune diseases. RHAMM mRNA
      was detectable in peripheral blood mononuclear cells (PBMN) of 60% of newly
      diagnosed AML patients. Western blotting stained positive for RHAMM protein in
      70% of AML patients. mRNA expression of RHAMM also was found in patients with CML
      (40%), renal cell carcinoma (73%), breast carcinoma (60%), and ovarian carcinoma
      (50%). In melanoma, RHAMM mRNA expression was detected in metastases (80%) but
      not in primary tumors. RHAMM is differentially expressed: significant mRNA
      expression was not found in normal tissues, except from testis, placenta, and
      thymus, or in PBMN- and CD34-separated cell samples of healthy volunteers.
      CONCLUSIONS: RHAMM is an immunogenic antigen in leukemias and solid tumors and
      might be a potential target structure for cellular immunotherapies and antibody
      therapies.

PMID- 12225793
TI  - Cyclopentenone prostaglandins induce caspase activation and apoptosis in
      dendritic cells by a PPAR-gamma-independent mechanism: regulation by inflammatory
      and T cell-derived stimuli.
AB  - OBJECTIVE: Dendritic cells (DC) are professional antigen-presenting cells playing
      a pivotal role in the induction of immunological responses. There is evidence
      that DC survival during ongoing immune responses is finite. However, little is
      known about the mechanisms regulating apoptosis in these cells. Here, we have
      investigated the effects of the anti-inflammatory cyclopentenone prostaglandins
      on human monocyte-derived DC. MATERIALS AND METHODS: Phenotype of DC was
      determined by flow cytometry and their allostimulatory potential in mixed
      leukocyte reaction. Induction of apoptosis in DC was monitored by staining with
      annexin-V-FITC and propidium iodide, propidium iodide staining of cell nuclei,
      and fluorimetric assay of caspase activity. Induction of maturation in DC was
      obtained by stimulation with TNF-alpha, LPS, IFN-gamma, CD40-ligand, or different
      combinations of these stimuli. PPAR-gamma expression in DC was determined by RT
      PCR. RESULTS: Exposure of immature DC to cyclopentenone prostaglandins blunted
      their allostimulatory capacity and skewed their phenotype by downregulating CD1a
      and costimulatory molecules. These effects were due to activation of caspases and
      induction of apoptotic cell death in DC by cyclopentenone prostaglandins. Mature
      DC showed enhanced susceptibility to apoptosis via cyclopentenone prostaglandins
      as compared with immature DC. Although DC express PPAR-gamma, the corresponding
      receptor for some of these metabolites, PPAR-gamma activation by a synthetic high
      affinity agonist failed to impair DC viability. CONCLUSIONS: Cyclopentenone
      prostaglandins induce apoptosis of human DC by a PPAR-gamma-independent
      mechanism. Since these compounds are released during an inflammatory event and
      show anti-inflammatory properties, they may contribute to the downregulation of
      DC function through apoptotic cell death.

PMID- 12225795
TI  - Reconstitution of functional human B lymphocytes in NOD/SCID mice engrafted with
      ex vivo expanded CD34(+) cord blood cells.
AB  - OBJECTIVE: Functional capacity of B cells developed from ex vivo expanded
      hematopoietic stem cells has not been fully evaluated. Therefore, we investigated
      the antigen-specific antibody production in human B cells maturated from ex vivo
      expanded cord blood (CB) CD34(+) cells in NOD/Shi-scid (NOD/SCID) mice. MATERIALS
      AND METHODS: CB CD34(+) cells were cultured for 5 days in the presence of human
      cytokines and the murine stromal cell line HESS-5, and transplanted into
      irradiated NOD/SCID mice. These mice, reconstituted with human hematopoietic
      cells, were challenged with T-cell-independent (TI) or T-cell-dependent (TD)
      antigens after CD19(+) cells appeared at 6 weeks. RESULTS: Three months later,
      anti-dinitrophenol (DNP)-specific antibody was detected in both mice immunized
      with DNP-Ficoll (TI) and those immunized with DNP-keyhole limpet hemocyanin or
      DNP-ovalbumin (TD). The anti-DNP antibody was mainly immunoglobulin M, but a
      small amount of immunoglobulin G also was detected. In the spleen, the majority
      of CD19(+) cells expressed mature B-cell markers such as CD40, immunoglobulin M,
      immunoglobulin D, cytoplasmic Cmu, and light chains kappa, and lambda.
      CONCLUSIONS: These results indicate that human B cells develop from CD34(+) cells
      in NOD/SCID mice to produce antigen-specific antibody with in vivo primary
      stimulation. This system provides a powerful and versatile tool for studying the
      entire process of human B-lymphocyte development and producing specific human
      monoclonal antibodies.

PMID- 12225796
TI  - The effects of pegylated recombinant human megakaryocyte growth and development
      factor (PEG-rHuMGDF) on platelet recovery in breast cancer patients undergoing
      autologous bone marrow transplantation.
AB  - OBJECTIVE: To assess the safety and efficacy of pegylated recombinant human
      megakaryocyte growth and development factor (PEG-rHuMGDF) administered after
      autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Two
      randomized, double-blind, placebo-controlled studies were done. In the phase 1/2
      study, 75 breast cancer patients underwent a bone marrow harvest and
      myeloablative STAMP V chemotherapy and were randomized to receive placebo or one
      of three doses of PEG-rHuMGDF. In the phase 3 study, 64 patients were randomized
      to receive placebo or the minimally effective dose of PEG-rHuMGDF. The study drug
      was administered daily starting on the day of bone marrow infusion until the
      platelet count was greater than or equal to 50 x 10(9)/L (without transfusion) or
      for a maximum of 28 days. All patients received 10 microg/kg/day filgrastim
      starting on day 2 until neutrophil count recovery. RESULTS: PEG-rHuMGDF appeared
      to be safe and well tolerated. No significant differences were noted in mortality
      or disease progression rates. Antibodies to MGDF were not observed. In the phase
      1/2 study, the time to platelet recovery to greater than or equal to 20 x 10(9)/L
      and platelet transfusion requirements were significantly reduced for patients
      treated with PEG-rHuMGDF compared with placebo (p < 0.05). In the phase 3 study,
      no significant differences in the kinetics of early thrombopoiesis or platelet
      transfusions after ABMT were observed. CONCLUSIONS: PEG-rHuMGDF was not
      consistently efficacious in reducing the duration of severe thrombocytopenia. The
      maximum platelet counts for PEG-rHuMGDF-treated patients occurred a median of 2
      weeks after the last dose of drug, suggesting that the biologic effects of this
      hematopoietic cytokine are delayed compared with other hematopoietic cytokines.

PMID- 12225797
TI  - Normal human bone marrow CD34(+)CD133(+) cells contain primitive cells able to
      produce different categories of colony-forming unit megakaryocytes in vitro.
AB  - OBJECTIVE: To evaluate the megakaryocyte potential of normal bone marrow (NBM)
      CD34(+)CD133(+) cells, a subset offering a possible alternative for clinical CD34
      immunoselection, we evaluated their colony-forming unit megakaryocyte (CFU-Mk)
      content and their ability to produce clonogenic Mk progenitors in comparison with
      the CD133(-) subset. MATERIALS AND METHODS: Sorted NBM CD34(+)CD133(+) and
      CD34(+)CD133(-) subsets were evaluated for Mk clonogenic capacity before and
      after in vitro proliferation in serum-free liquid culture containing kit ligand,
      Flt3 ligand, thrombopoietin, interleukin-3, and interleukin-6. The segregation of
      CFU-Mk according to the expression of CD34, CD133, and CD41 was compared between
      fresh BM cells and expanded cells. RESULTS: Although the fresh NBM CD133(
      )CD34(+) subset included two thirds CFU-Mk, only the CD133(+) subset contained
      primitive cells able to produce all categories of CFU-Mk in vitro.
      Immunophenotyping confirmed that CD41 antigen is nonspecific for Mk lineage and
      showed that the usual CD34(+)CD41(+) subset does not specifically define a CFU-Mk
      population. The segregation of CFU-Mk before and after expansion according to
      CD34, CD41, or CD133 was modified in relation with down-regulation of CD34 and
      CD133 antigens and up-regulation of CD41 antigen. CONCLUSIONS: The NBM CD133(+)
      subset contains primitive cells able to generate CFU-Mk, a subset probably
      relevant to platelet recovery after infusion. The alteration of antigen
      expression during in vitro proliferation calls for caution in the identification
      of the different categories of Mk subsets produced and in the assessment of their
      predictivity for in vivo platelet production.

PMID- 12225798
TI  - Treatment of circulating CD34(+) cells with SDF-1alpha or anti-CXCR4 antibody
      enhances migration and NOD/SCID repopulating potential.
AB  - OBJECTIVE: Stromal cell-derived factor-1alpha (SDF-1alpha) has been implicated in
      homing and engraftment of primitive hematopoietic progenitor cells (HPC) in
      studies demonstrating reduced NOD/SCID repopulating potential of HPC exposed to
      supra-physiologic concentrations of SDF-1alpha or anti-CXCR4. Outcome of CXCR4
      signaling in some cells has been shown to be dependent on the concentration of
      SDF-1alpha. We aimed to determine whether similar concentration-dependent
      responses to CXCR4 signaling are present in CD34(+)cells. MATERIALS AND METHODS:
      Human peripheral blood (PB), mobilized PB (MPB), or bone marrow (BM) CD34(+)
      cells were incubated for 30 minutes with different concentrations of SDF-1alpha
      or anti-CXCR4, washed, then assessed for in vitro hematopoietic potential,
      migration, and NOD/SCID repopulating potential. RESULTS: Exposure of MPB or PB
      CD34(+) cells to 100 ng/mL SDF-1alpha increased tyrosine phosphorylation without
      subsequent proliferation or apoptosis. Spontaneous and SDF-1alpha-directed
      migration also increased in pretreated cells, despite previous exposure to SDF
      1alpha. Cells exposed to 1 microg anti-CXCR4/10(6) cells displayed similar
      increases in activation and migration as cells exposed to SDF-1alpha,
      demonstrating the ability of anti-CXCR4 to activate the CXCR4 receptor.
      Interestingly, chimerism in NOD/SCID mice transplanted with MPB CD34(+) cells
      pretreated with SDF-1alpha or anti-CXCR4 was increased, while exposure of these
      cells to 10- to 100-fold higher concentrations of these proteins inhibited in
      vitro migration and NOD/SCID repopulating potential. Migration and NOD/SCID
      repopulating potential of BM CD34(+) cells remained unchanged after treatment
      with either protein. CONCLUSIONS: These results illustrate the ability of SDF
      1alpha and anti-CXCR4 to augment repopulating potential of CD34(+) cells, and
      suggest that HPC function can be favorably modulated through specific CXCR4
      signaling.

PMID- 12225799
TI  - Definitive hematopoietic commitment within the embryonic vascular endothelial
      cadherin(+) population.
AB  - OBJECTIVE: The aim of this study was to assess the potential of FLK1(+) and
      vascular endothelial (VE)-cadherin(+) populations from different stages of
      embryonic development to generate hematopoietic cells ex vivo and to contribute
      to the hematopoietic systems of recipient mice. MATERIALS AND METHODS: FLK1(+) of
      VE-cadherin(+) cells were isolated from 7.5- to 9.5-dpc concepti and cultured ex
      vivo on OP9 stromal cells and hematopoietic development examined. VE
      cadherin(+)CD45(-) cells from 8.5- and 9.5-dpc concepti were injected
      intrahepatically into newborn busulfan-treated SCID recipients and engraftment
      monitored. RESULTS: VE-cadherin(+) cells from 7.5- and 8.5-dpc concepti can
      readily generate hematopoi-etic cells ex vivo compared to FLK1(+) VE-cadherin(-)
      cells. Similar hematopoietic potential can be found in the VE-cadherin(+) cells
      from the 8.5-dpc yolk sac. When VE-cadherin(+)CD45(-) cells were injected into
      SCID recipients, long-term engraftment, particularly within the lymphoid system,
      was observed. This potential was observed in VE-cadherin(+)CD45(-) cells from 9.5
      dpc embryo or yolk sac but from tissues from younger concepti. CONCLUSIONS:
      FLK1(+)VE-cadherin(-) cells, possibly representing the lateral plate mesoderm,
      are not as effective at generating hematopoietic cells compared to similarly
      staged VE-cadherin(+) cells. VE-cadherin(+)CD45(-) cells can also contribute to
      the hematolymphoid system of intrahepatically injected newborn SCID recipients,
      suggesting that cells bearing an endothelial phenotype are capable of generating
      long-term hematopoietic precursors.

PMID- 12225800
TI  - Ex vivo expansion of megakaryocyte progenitors from cryopreserved umbilical cord
      blood. A potential source of megakaryocytes for transplantation.
AB  - OBJECTIVE: Umbilical cord blood (CB) provides an alternative source of
      hematopoietic progenitor cells for transplantation; however, prolonged
      thrombocytopenia remains a major obstacle due to the low numbers of megakaryocyte
      progenitor (Mk-prog) cells and their subsequent delayed engraftment. In this
      study, we improved techniques for enrichment, cryopreservation, and ex vivo
      expansion of Mk-prog cells from CB. MATERIALS AND METHODS: CB mononuclear cells
      (MNC) were isolated and Mk-prog enriched by sedimentation on gelatin followed by
      centrifugation with Ficoll-Hypaque and cryopreserved. The capacity of MNC to
      produce Mk-prog cells, assessment of CD34(+) and Mk-prog expansion in liquid
      culture, and analysis of the cell populations by flow cytometry were studied in
      cryopreserved separated CB and compared to whole CB and freshly separated
      samples. RESULTS: Excellent viability of greater than 85% was maintained after
      cryopreservation of separated CB. The number of colony-forming Mk-prog, myeloid,
      and erythroid progenitor cells did not decrease with cryopreservation. Flow
      cytometric analysis of cryopreserved cells revealed significant removal of the
      residual red blood cells while maintaining complete recovery of CD34(+), CD41(+)
      (Mk), myeloid, and T and B cells compared to noncryopreserved CB cells. There was
      no difference in the ability of separated cryopreserved MNC CB cells to be
      expanded in short-term liquid cultures. CONCLUSIONS: The conditions defined here
      for cryopreservation of gelatin/Ficoll-Hypaque separated CB, followed by ex vivo
      expansion of MNC, allowed complete recovery of proliferating CD41(+), CD34(+), Mk
      prog cells, and other hematopoietic progenitors. Mk-prog cell expansion just
      before the scheduled transplantation is easily applicable by this technically
      simple and economical procedure that requires only an aliquot of red cell cell
      depleted MNC to be separated from the CB unit before cryopreservation.

PMID- 12225801
TI  - Circulating gelatinase B (MMP-9)--the impact of the preanalytical step of blood
      collection.

PMID- 12225802
TI  - Isolation of ovocleidin-116 from chicken eggshells, correction of its amino acid
      sequence and identification of disulfide bonds and glycosylated Asn.
AB  - Fractionation of the soluble chicken eggshell matrix by chromatographic methods
      yielded 13 endogenous proteolytic fragments of the eggshell-specific proteoglycan
      core protein ovocleidin-116. The N-terminal amino acid sequences of these
      fragments in general confirmed the recently cDNA-deduced sequence of ovocleidin
      116, with one exception. One fragment yielded a completely new sequence and was
      instrumental in detecting a frame shift error in the nucleotide sequence. The
      correction yielded a new sequence which was 38 amino acids shorter than before
      and contained a 57-amino acid long novel C-terminal sequence. The predicted
      sequence of ovocleidin-116 contained two consensus N-glycosylation sites, only
      one of which (Asn62) was found to be fully modified. A disulfide bond was
      identified between Cys31 and 42 implying that Cys329 and 421 form a second
      disulfide bond. Finally, the yield of fragments indicated that ovocleidin-116 is
      a major component of the chicken eggshell matrix.

PMID- 12225803
TI  - Association of a polymorphism of the matrix metalloproteinase-1 gene with bone
      mineral density.
AB  - Matrix metalloproteinase-1 (MMP-1) is a key mediator of the degradation of
      collagen, which is abundant in bone matrix. A nucleotide polymorphism (G --> GG)
      at position -1607 in the promoter of the MMP-1 gene is associated with increased
      gene transcription. The possible relation of the -1607G --> GG polymorphism of
      the MMP-1 gene to bone mineral density (BMD) was examined in a population-based
      study with 1095 women and 1127 men. BMD for the distal radius was significantly
      lower in postmenopausal women with the GG/GG genotype than in those with the G/GG
      or those with the G/G or G/GG genotype; these differences were not apparent in
      premenopausal women. No significant differences in BMD at other sites were
      detected among MMP-1 genotypes for women. Men did not exhibit any significant
      differences in BMD among MMP-1 genotypes. The MMP-1 gene may thus be a
      susceptibility locus for reduced BMD at the distal radius in postmenopausal
      women.

PMID- 12225804
TI  - Specific immunological detection of the (V+C)(-) fibronectin isoform.
AB  - The population of fibronectins in adult mammalian cartilage includes high levels
      of a cartilage-specific (V+C)(-) isoform which lacks the V, III-15, and I-10
      segments and thus contains a novel junction between protein segments III-14 and I
      11. We report production of a monoclonal antibody specific for (V+C)(-)
      fibronectin without cross-recognition of V(+)C(+) and V(-)C(+) isoforms found in
      plasma and other tissues. Presentation of epitope to this antibody requires the
      III-14/I-11 junction, but the epitope itself extends beyond 14 amino acids
      immediately surrounding the junction site and involves a conformational change in
      III-14 and/or the N-terminal portion of I-11. The antibody, designated Mab 5D10
      anti (V+C)(-), displays specificity for (V+C)(-) fibronectin from multiple
      mammalian species including humans and utility in immunoblots,
      immunohistochemistry, and ELISA.

PMID- 12225805
TI  - Human fibronectin and MMP-2 collagen binding domains compete for collagen binding
      sites and modify cellular activation of MMP-2.
AB  - The region of fibronectin (FN) surrounding the two type II modules of FN binds
      type I collagen. However, little is known about interactions of this collagen
      binding domain with other collagen types or extracellular matrix molecules. Among
      several expressed recombinant (r) human FN fragments from the collagen binding
      region of FN, only rI6-I7, which included the two type II modules and both
      flanking type I modules, bound any of several tested collagens. The rI6-I7
      interacted specifically with both native and denatured forms of types I and III
      collagen as well as denatured types II, IV, V and X collagen with apparent K(d)
      values of 0.2-3.7 x 10(-7) M. Reduction with DTT disrupted the binding to gelatin
      verifying the functional requirement for intact disulfide bonds. The FN fragments
      showed a weak, but not physiologically important, binding to heparin, and did not
      bind elastin or laminin. The broad, but selective range of ligand interactions by
      rI6-I7 mirrored our prior observations for the collagen binding domain (rCBD)
      from matrix metalloproteinase-2 (MMP-2) [J. Biol. Chem. 270 (1995) 11555].
      Subsequent experiments showed competition between rI6-I7 and rCBD for binding to
      gelatin indicating that their binding sites on this extracellular matrix molecule
      are identical or closely positioned. Two collagen binding domain fragments
      supported cell attachment by a beta1-integrin-dependent mechanism although
      neither protein contains an Arg-Gly-Asp recognition sequence. Furthermore,
      activation of MMP-2 and MMP-9 was greatly reduced for HT1080 fibrosarcoma cells
      cultured on either of the fibronectin fragments compared to full-length FN. These
      observations imply that the biological activities of FN in the extracellular
      matrix may involve interactions with a broad range of collagen types, and that
      exposure to pathologically-generated FN fragments may substantially alter cell
      behavior and regulation.

PMID- 12225806
TI  - Collagen IV in the developing lens capsule.
AB  - The lens capsule is a specialized thickened basement membrane that completely
      surrounds the lens and provides anchoring sites for zonules, the filamentous
      bodies that suspend the lens. Like other basement membranes, the lens capsule
      contains collagen IV, which is a family of six polypeptides, subunits alpha1(IV)
      alpha6(IV), each of which is encoded by a distinct gene. We have investigated the
      presence of collagen IV subunits in the developing lens capsule by using confocal
      immunohistochemistry and antibodies against each of the six collagen IV subunits.
      In murine embryos, subunits alpha1(IV), alpha2(IV), alpha5(IV) and alpha6(IV)
      were detected in the basement membrane surrounding the lens vesicle, and they
      persisted in the capsule until adulthood. In contrast, neither collagen
      alpha3(IV) nor alpha4(IV) was detected in the lens capsule until 2 weeks
      postnatal. Similarly, we detected no collagen alpha3(IV) or alpha4(IV) in lens
      capsules of 54-day human embryos, while collagen alpha3(IV) and alpha4(IV) were
      detected in adult humans. Thus, in the lens capsule, there is a developmental
      shift in detectable collagen IV subunits; early in development we observed
      subunits alpha1(IV), alpha2(IV), alpha5(IV) and alpha6(IV), which is consistent
      with the presence of fibrillar [alpha1alpha1alpha2] and elastic
      [alpha5alpha5alpha6] protomers, but later in development components of the more
      cross-linked [alpha3alpha4alpha5] protomer appear. An elastic lens capsule may be
      necessary in order to accommodate rapid lens growth in early development, whereas
      later in development a stronger, more cross-linked capsule may be necessary in
      order to tolerate the stress caused by postnatal accommodation and
      disaccommodation of the lens.

PMID- 12225807
TI  - Matrix metalloproteinases are active following guanidine hydrochloride extraction
      of cartilage: generation of DIPEN neoepitope during dialysis.
AB  - We have recently observed marked increases in MMP-derived aggrecan fragments in
      extracts of cartilage stimulated with IL-1. The fragments were detected with an
      anti-DIPEN neoepitope antibody that is specific for fragments generated by MMP
      cleavage at the DIPEN(341) F(342)FGVG site. Because our results contrasted with
      another study, we systematically compared our methods with other published
      methods. We now report that DIPEN(341) neoepitope can be generated post-culture,
      by dialysing GuHCl(1)-denatured samples against unbuffered, deionized water at 4
      degrees C. We show that EDTA must be included in the GuHCl extractant, as well as
      the dialysis buffer, in order to block post-culture processing of aggrecan by
      MMPs.

PMID- 12225808
TI  - Highly sulfated glycosaminoglycans inhibit aggrecanase degradation of aggrecan by
      bovine articular cartilage explant cultures.
AB  - The catabolism of 35S-labeled aggrecan and loss of tissue glycosaminoglycans was
      investigated using bovine articular cartilage explant cultures maintained in
      medium containing 10(-6) M retinoic acid or 40 ng/ml recombinant human
      interleukin-1alpha (rHuIL-1alpha) and varying concentrations (1-1000 microg/ml)
      of sulfated glycosaminoglycans (heparin, heparan sulfate, chondroitin 4-sulfate,
      chondroitin 6-sulfate, dermatan sulfate and keratan sulfate) and calcium pentosan
      polysulfate (10 microg/ml). In addition, the effect of the sulfated
      glycosaminoglycans and calcium pentosan polysulfate on the degradation of
      aggrecan by soluble aggrecanase activity present in conditioned medium was
      investigated. The degradation of 35S-labeled aggrecan and reduction in tissue
      levels of aggrecan by articular cartilage explant cultures stimulated with
      retinoic acid or rHuIL-1alpha was inhibited by heparin and heparan sulfate in a
      dose-dependent manner and by calcium pentosan polysulfate. In contrast,
      chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate and keratan
      sulfate did not inhibit the degradation of 35S-labeled aggrecan nor suppress the
      reduction in tissue levels of aggrecan by explant cultures of articular
      cartilage. Heparin, heparan sulfate and calcium pentosan polysulfate did not
      adversely affect chondrocyte metabolism as measured by lactate production,
      incorporation of [35S]-sulfate or [3H]-serine into macromolecules by articular
      cartilage explant cultures. Furthermore, heparin, heparan sulfate and calcium
      pentosan polysulfate inhibited the proteolytic degradation of aggrecan by soluble
      aggrecanase activity. These results suggest that highly sulfated
      glycosaminoglycans have the potential to influence aggrecan catabolism in
      articular cartilage and this effect occurs in part through direct inhibition of
      aggrecanase activity.

PMID- 12225809
TI  - Opposite effects of thrombospondin-1 via CD36 and CD47 on homotypic aggregation
      of monocytic cells.
AB  - Thrombospondin-1 (TSP-1), an extracellular matrix protein, has a multimodular
      structure and each domain specifies a distinct biological function through
      interaction with a specific ligand. In this study we found that exogenously added
      TSP-1 inhibits phorbol myristate acetate (PMA)/LPS-induced homotypic aggregation
      of human monocytic U937 cells, whereas the 70-kDa fragment of TSP-1 generated by
      the proteolytic cleavage of the intact molecule promotes the homotypic
      aggregation. The aggregation was also inhibited by anti-CD47 mAb or the 4N1K
      peptide, of which sequence is derived from the CD47-binding site of TSP-1 and
      absent in the 70-kDa fragment. In contrast, the augmented cell aggregation by the
      70-kDa fragment was hampered by anti-CD36 mAb or antibody against the CD36
      binding site of TSP-1. The cell aggregation of U937 cells was completely blocked,
      even in the presence of the 70-kDa fragment, by mAb against leukocyte function
      associated antigen-1 (LFA-1) or intercellular adhesion molecule-1 (ICAM-1). We
      therefore propose that TSP-1 may regulate LFA-1/ICAM-1-mediated cell adhesion of
      monocytes/macrophages by either the inhibitory effect through CD47 or the
      promoting effect through CD36 depending on which domain/fragment is functional in
      a given biological setting.

PMID- 12225810
TI  - Response of young, aged and osteoarthritic human articular chondrocytes to
      inflammatory cytokines: molecular and cellular aspects.
AB  - The aim of this study was to investigate the metabolic properties of human
      articular chondrocytes derived from young, aged and osteoarthritic subjects and
      their genetic adaptation to a catabolic challenge (i.e. the inflammatory
      cytokines interleukin-1alpha and tumor necrosis factor-alpha), in the absence or
      presence of diacerein, a drug potentially useful in osteoarthritis. Chondrocytes
      in primary culture were analyzed for newly secreted proteins, metalloproteinase
      synthesis and activity, and production of nitric oxide by-products. Results show
      that chondrocytes from normal but aged subjects present biochemical properties
      closer to osteoarthritic-derived cartilage than to normal young cartilage, as
      indicated by cell morphology, cell proliferation rate and pattern of protein
      secretion (in particular stromelysin-1 and interstitial collagenase). According
      to patient age and cartilage physiopathology, chondrocytes secrete increasing
      amounts of a protein identified by micro-sequencing as chitinase-like protein.
      Upon exposure to the inflammatory cytokines, chondrocytes, regardless the age or
      the status of the donor, significantly enhance their production of stromelysin-1,
      interstitial collagenase, interleukin-6 and interleukin-8. By contrast, the
      chitinase-like protein is not modulated by the cytokines. The pattern of protein
      secretion and metalloproteinase activity in chondrocytes from aged subjects
      appeared to be different from that of young patients, but was highly expressed in
      osteoarthritic chondrocytes. Diacerein, at therapeutically useful concentrations,
      consistently counteracts the stimulatory effect of cytokines on newly secreted
      proteins, metalloproteinase activity and nitric oxide production, whereas a
      selective nitric oxide blocker alone is ineffective. These data demonstrate that
      a specific gene program is turned on in cytokine-stimulated chondrocytes, which
      involves production of proteins engaged in remodeling and destruction of
      cartilage matrix. Part of these mechanisms appears to be operative also in
      unstimulated aged chondrocytes. Diacerein largely prevents the metabolic
      alterations caused by cytokine exposure in human chondrocytes, possibly through
      its ability to block early intracellular mediators after cytokine stimulation,
      such as oxygen radicals.

PMID- 12225811
TI  - Matrix-matrix interaction of cartilage oligomeric matrix protein and fibronectin.
AB  - Recent work indicates that cartilage oligomeric matrix protein (COMP) plays an
      important role in extracellular matrix assembly and matrix-matrix protein
      interactions. In order to identify the proteins in extracellular matrix that
      interact with COMP, we used an ELISA-based solid-phase binding assay, which
      revealed a specific, high-affinity interaction between COMP and fibronectin. This
      interaction is concentration-dependent and saturable, and appears to occur under
      physiologically relevant conditions. Electron microscopy after negative staining
      and fragment binding analysis using the solid-phase assay revealed a predominant
      binding site for the COMP C-terminal globular domain to a molecular domain
      approximately 14 nm from the N-terminal domain of fibronectin, which can be
      inhibited by the presence of a polyclonal antibody specific for the C-terminal
      heptadecapeptide of COMP. This interaction is further demonstrated in vivo by
      colocalization of both COMP and fibronectin in the chondrocyte pericellular
      matrix by laser confocal microscopy of chondrocytes grown in agarose culture, and
      by appositional and colocalization of these proteins in the growth plate of
      primates by immunohistochemistry.

PMID- 12225812
TI  - High level of Fc epsilon receptor I-bindable immunoglobulin E in the tear fluid
      and increased immunoglobulin E-saturated cells in the giant papillae of vernal
      keratoconjunctivitis patients.
AB  - PURPOSE: To investigate the concentrations of Fc epsilon receptor I (Fc epsilon
      RI)-bindable immunoglobulin E (IgE) in the tear fluid and the proportion of IgE
      saturated cells among Fc epsilon RI-positive cells in giant papillae from vernal
      keratoconjunctivitis (VKC) patients. METHODS: The tear fluids and giant papillae
      were obtained from 8 VKC patients with their informed consent. To detect the
      quantitative difference between Fc epsilon RI-bindable IgE and total IgE in the
      tear fluid, we used a new enzyme-linked immunosorbent assay system we have
      developed. Next, to estimate the proportion of IgE-saturated cells among Fc
      epsilon RI-positive cells, we used two distinct monoclonal antibodies for Fc
      epsilon RI for the immunohistochemistry. One antibody recognizes all Fc epsilon
      RI regardless of whether it is with or without receptor-bound IgE. The other does
      not recognize IgE-bound Fc epsilon RI. RESULTS: The quantitative difference
      between Fc epsilon RI-bindable IgE and total IgE were detected in the tear fluid
      of VKC patients. Fc epsilon RI-positive cells were significantly increased in the
      giant papillae of VKC compared with normal conjunctivae. The proportion of IgE
      saturated cells among Fc epsilon RI-positive cells in giant papillae was higher
      than that in normal conjunctivae. CONCLUSION: These results suggest that F
      epsilon RI-bindable IgE may be a critical factor to estimate the severity of VKC.

PMID- 12225813
TI  - Histological study of conjunctiva-associated lymphoid tissue in mouse.
AB  - PURPOSE: To investigate conjunctiva-associated lymphoid tissue (CALT) in the
      mouse conjunctiva by histological methods. METHODS: The presumed follicular
      tissue in the conjunctiva of normal mice, age ranging from 4 to 6 weeks, was
      histologically investigated by the hematoxylin-eosin staining method. Next, we
      treated the mice with topical instillation of a combined solution of ovalbumin
      and cholera toxin B to investigate the morphological changes of conjunctival
      follicles to antigen challenge. The treated mice underwent sequential clinical
      examinations, and the conjunctival follicular tissue was examined by an
      immunohistochemical method using anti-CD4 antibody, anti-CD8 antibody, and anti-S
      100 antibody. RESULTS: Follicular tissue was present on the mouse nictitating
      membrane. Both size and number of follicular tissue areas increased with topical
      ovalbumin treatment. Immunohistochemical study revealed CD4, CD8, and S-100
      positive cells in the follicular tissue. The epithelial layer, corresponding to
      follicular tissue, demonstrated intra-epithelial pocket and the presence of CD4
      positive cells in the intra-epithelial pocket. CONCLUSION: Follicular tissue at
      the nictitating membrane is CALT in the mouse.

PMID- 12225814
TI  - The effect of immunization with herpes simplex virus glycoprotein D fused with
      interleukin-2 against murine herpetic keratitis.
AB  - PURPOSE: To evaluate the preventive effect of vaccination using fusion protein
      (gD-IL-2) consisting of herpes simplex virus type 1 (HSV-1) glycoprotein D (gD),
      and human interleukin-2 (IL-2), and plasmid DNA encoding gD-IL-2 against murine
      herpetic keratitis. METHODS: Plasmid containing gD-IL-2 (pHDLneo1) was
      constructed, and gD-IL-2 peptide was purified. BALB/c mice were injected
      hypodermally or subconjunctivally twice with 1 microg/0.1 mL of gD-IL-2 peptide,
      or subconjunctivally twice with 90 microg/0.05 mL of gD-IL-2 plasmid DNA.
      Neutralizing antibody titer and delayed-type hypersensitivity (DTH) against HSV-1
      were measured. Immunized mice were challenged with CHR3 strain of HSV-1 into the
      cornea. Clinical manifestations of the epithelial and stromal keratitis were
      scored. RESULTS: Stromal keratitis was inhibited in gD-IL-2 peptide- or DNA
      immunized mice; however, epithelial keratitis was not. It was confirmed that
      plasmid gD-IL-2 elicited significant virus neutralizing titer in sera and DTH
      response. CONCLUSION: Vaccination with gD-IL-2 was effective against murine
      herpetic keratitis.

PMID- 12225815
TI  - Development of novel corneal storage medium: first report. Examinations of rabbit
      cornea.
AB  - PURPOSE: To develop a new corneal storage medium with a simple formula and
      evaluate it by histological methods. METHODS: Two corneal storage media
      containing minimum essential medium and 2.5% chondroitin sulfate (pH 7.33), with
      osmolarity of 320 mOsm/kg, were compared to Optisol-GS. The differences in the
      two media were the molecular weight (MW) and the source of chondroitin sulfate.
      The MW of Medium I was 27,500 and the MW of Medium II was 33,700. Japanese albino
      rabbits were used in this study. A cornea with scleral rim obtained from a rabbit
      was stored in either Medium I or Medium II and the fellow cornea was stored in
      Optisol-GS for 7 or 14 days at 4 degrees C. Histological examination of corneal
      endothelial cells was performed both by scanning electron microscopy and by
      transmission electron microscopy. RESULTS: At day 7, there was no significant
      difference in histological findings among the rabbit corneas stored in Optisol
      GS, Medium I, or Medium II. At day 14, corneas stored in Optisol-GS or Medium I
      showed similar histological findings. In Medium II, endothelial cells showed
      marked degeneration. CONCLUSIONS: The results of experiments with rabbit cornea
      indicated that Optisol-GS and Medium I could preserve endothelial cellular
      structure better than Medium II. The difference between Medium I and Medium II
      was only the MW of the chondroitin sulfate used. The MW may be an important
      factor for determining suitable chondroitin sulfate for use in a corneal storage
      medium.

PMID- 12225816
TI  - General purpose antimicrobial ophthalmic solutions evaluated using new
      pharmacokinetic parameter of maximum drug concentration in aqueous.
AB  - PURPOSE: In order to determine whether the one-component method for calculating
      drug concentration in the aqueous (AQC(max)) is useful for selecting an
      appropriate ophthalmic solution, six general purpose antimicrobial ophthalmic
      solutions already on the market were investigated. METHODS: The drugs examined
      were levofloxacin (LVFX), chloramphenicol (CP), erythromycin lactobionate (EM),
      micronomicin sulfate (MCR), cefmenoxime hydrochloride (CMX), and disodium
      sulfobenzyl penicillin (SBPC). Fifty microliters of each solution was instilled
      into the cul-de-sac of New Zealand White rabbit eyes three times at 15-minute
      intervals. The drug concentrations in the aqueous humor 10, 30, 60, 120, and 240
      minutes after the final instillation were examined by high performance liquid
      chromatography (HPLC) and/or bioassay. The AQC(max) was calculated using the one
      compartment method. RESULTS: The calculated AQC(max) was 2.5 microg/mL (HPLC
      method) and 2.28 microg/mL (bioassay method) for LVFX, 2.17 microg/mL for CP, and
      0.45 microg/mL for EM. The AQC(max) for CMX, MCR, and SBPC could not be
      calculated by the one-compartment method. CONCLUSIONS: The AQC(max) of LVFX was
      higher than that of the two other general purpose antimicrobial ophthalmic
      solutions. The AQC(max) of these drugs might be a useful parameter for selecting
      an appropriate ophthalmic solution for the treatment of infected eyes.

PMID- 12225817
TI  - Response of the mouse lens to varying sizes of injured area.
AB  - PURPOSE: To examine the response of the lens to varying sizes of perforating
      injury. METHODS: Four-week-old mice were used. Injuries consisted of pricking in
      the central region of the lens by transcorneal insertion of needles of two
      different sizes. After injury, the eyeballs were removed sequentially at various
      intervals up to 30 days and examined morphologically. RESULTS: The mouse lens
      showed three patterns of reaction; retained transparency, posterior opacity, and
      anterior opacity. (1) When the lens remained clear, the injury was small in area.
      The damaged portion of the lens was repaired by epithelial proliferation. (2)
      When opacity occurred abruptly at the posterior cortical area, epithelial damage
      was mild and lens fiber damage was relatively severe. Evans blue dye moved toward
      the posterior polar region along the cortical fiber arrangement. (3) When opacity
      developed abruptly at the anterior cortex, the size of epithelial damage and the
      damage to lens fibers were extensive. The posterior cortex remained transparent.
      Evans blue dye remained in the anterior polar region just beneath the injured
      part. CONCLUSION: It was found that the size of the injured area is a determinant
      of repair or opacity, and the site of opacity is dependent on the severity of
      epithelial damage and the location of the liquefied area.

PMID- 12225818
TI  - Effect of latanoprost, prostaglandin F(2)alpha and nipradilol on isolated bovine
      ciliary muscle.
AB  - PURPOSE: Ciliary muscle tone is considered to be an important factor for control
      of uveoscleral outflow. In an attempt to clarify the functional roles of the
      ciliary muscle in uveoscleral outflow, the effects of latanoprost, prostaglandin
      (PG)F(2)alpha or nipradilol, all of which are known to increase uveoscleral
      outflow, were investigated, using the bovine ciliary muscle. METHODS: We isolated
      longitudinal ciliary muscle from bovine eyes and investigated the effects of
      these three agents on the mechanical properties of this muscle using isometric
      tension recording methods. RESULTS: Latanoprost and PGF(2)alpha evoked small but
      discrete contractions at a concentration of 0.1 microM even during the sustained
      contraction evoked by 10 mM acetylcholine (ACh). However, nipradilol did not
      evoke any response at concentrations up to 0.1 mM. None of these agents had an
      effect on the amplitude of the ciliary muscle twitch contraction evoked by
      electrical field stimulation. CONCLUSIONS: Our findings indicate that these three
      agents have no relaxant effect on isolated bovine ciliary muscle even during the
      sustained contraction evoked by ACh. Further, these agents had no effect on the
      contraction evoked by field stimulation, which indicates that the drugs have no
      presynaptic effects. These results are inconsistent with the hypothesis that
      drugs that increase uveoscleral outflow relax the ciliary muscle with a
      consequent increase in uveoscleral outflow. Further investigation of the role of
      ciliary muscle contractility on uveoscleral outflow is warranted.

PMID- 12225819
TI  - Relationship between glycoxidation and cytokines in the vitreous of eyes with
      diabetic retinopathy.
AB  - PURPOSE: To investigate the correlations among pentosidine, an advanced glycation
      end product, and related cytokines (vascular endothelial growth factor [VEGF],
      transforming growth factor [TGF]-beta(2), and monocyte chemotactic protein [MCP]
      1), and active oxygen in the vitreous of patients with diabetic retinopathy (DR).
      METHODS: Vitreous samples from 43 eyes that underwent vitrectomy to treat DR were
      divided into four subgroups and analyzed. Vitreous samples from 21 eyes of
      patients with no systemic conditions served as age- and sex-matched controls. The
      vitreous levels of pentosidine, cytokines, and hydrogen peroxide (H(2)O(2)) were
      determined by high-performance liquid chromatography, enzyme-linked immunosorbent
      assay, and the titanium-hydrogen peroxide colorimetric method, respectively.
      RESULTS: The levels of pentosidine, VEGF, total TGF-beta(2), and MCP-1 in the
      vitreous samples of eyes with DR were significantly higher than in the controls
      (P <.01). Significant correlations (P <.01) were found between pentosidine and
      VEGF, pentosidine and H(2)O(2), H(2)O(2) and VEGF, and total TGF-beta(2) and MCP
      1 (r = 0.62, 0.58, 0.65, and 0.59, respectively). CONCLUSIONS: These results
      suggest that elevated levels of pentosidine may cause increased levels of VEGF in
      the vitreous of patients with DR. Increased levels of total TGF-beta(2) and MCP-1
      together also might play an important role in the development of DR.

PMID- 12225821
TI  - Reliability and significance of measurements of a-wave latency in rats.
AB  - PURPOSE: To determine whether measurements of the a-wave latency of the
      electroretinogram (ERG) can be made as reliably as that of the implicit time (IT)
      in rats. In addition, to determine the relationship between the potential level
      selected for the latency and the baseline potential level. METHODS: ERGs,
      elicited by different stimulus intensities, were recorded from Long-Evans rats.
      The a-wave latency was determined by measuring the time between the stimulus
      onset and the beginning of the negative-going a-wave, and the IT was measured as
      the time between the stimulus onset and the peak of the a-wave. To test the
      reliability of the measurements of the latency, the a-wave latency and the IT
      were measured by three independent observers for the same 15 ERGs. RESULTS: The
      mean a-wave latency was approximately 14 milliseconds, and the mean a-wave
      implicit time was approximately 36 milliseconds. The mean of the a-wave latency
      and the IT, as measured by the three observers, were within 1 millisecond of each
      other. The coefficient of variation was as good for the latency as for the IT of
      the a-wave. The potential level selected for the latency was lower than the mean
      baseline potential level by 1 to 2 standard deviations. CONCLUSIONS: Selection of
      the a-wave latencies can be made as reliably as that for the IT. Because the a
      wave latency is not affected by the activity of the second order neurons, the
      latency is a better measure than the IT of the time course of the a-wave.

PMID- 12225820
TI  - Retinal glial cells stimulate microvascular pericyte proliferation via fibroblast
      growth factor and platelet-derived growth factor in vitro.
AB  - PURPOSE: To investigate whether retinal glial cells (RGCs), which are believed to
      play an important role in the development and maintenance of microvessels,
      stimulate the proliferation of retinal bovine microvascular pericytes, an
      essential component of the vessels. METHODS: Conditioned medium (CM) was
      collected from a primary culture of RGC obtained from chick embryonic retina. The
      cell number was assayed after stimulation by RGC-CM. Also, by neutralizing
      antibody and reverse transcription polymerase chain reaction (RT-PCR), we tried
      to identify which factor of the RGCs contributes to the pericyte stimulation.
      RESULTS: Pericyte proliferation was stimulated by RGC-CM in a dose-dependent
      manner. Platelet-derived growth factor-BB (PDGF-BB), acidic fibroblast growth
      factor (aFGF), and basic fibroblast growth factor (bFGF) stimulated pericyte
      proliferation; however, PDGF-AA, transforming growth factor-beta2 (TGF-beta2),
      and vascular endothelial growth factor (VEGF) did not. The RGC-CM-dependent
      stimulative effect was blocked, in part, by the neutralizing antibodies for aFGF,
      bFGF, and PDGF. A mixture of these three antibodies completely blocked the
      stimulation. RT-PCR revealed that RNA for aFGF, bFGF, and TGF-beta2 were
      expressed in RGCs. CONCLUSIONS: Pericyte growth is stimulated in vitro by RGC-CM
      through aFGF, bFGF, PDGF-BB, at least in part. This finding suggests that RGCs
      may modulate in vivo pericyte cell growth through these three growth factors.

PMID- 12225822
TI  - Evidence that a-wave latency of the electroretinogram is determined solely by
      photoreceptors.
AB  - PURPOSE: To identify the retinal cells that determine the a-wave latency of rats.
      METHODS: Electroretinograms (ERGs) were recorded from the rod-dominated (0.85%
      cones) retinas of Long-Evans rats following an intravitreal injection of 1 microL
      of 40 mM 2-amino-4-phosphonobutyric acid to block the activity of the ON pathway
      of the second order retinal neurons. ERGs were also recorded following an
      intraperitoneal injection of sodium iodate to destroy the retinal pigment
      epithelial (RPE) cells. Damage to a large area of the retina was produced by
      constant light exposure, and focal damage to the retina was induced by argon
      laser photocoagulation. The effects of age and anesthesia level on the a-wave
      latency were also determined. RESULTS: Blocking the activity of the ON pathway of
      the second order retinal neurons did not alter the a-wave latency, and destroying
      the RPE cells also did not alter the a-wave latency. Damage to a large area of
      the retina resulted in prolonging the latency but focal retinal damage did not
      alter the a-wave latency. The a-wave latency was longer in young rat pups but was
      adult-like by 18 days. The level of anesthesia had no effect on the latency
      except at very deep stages. CONCLUSIONS: The a-wave latency is determined solely
      by the activity of the photoreceptors. A prolonged latency would indicate that
      the photoreceptors are damaged over a large area of the retina.

PMID- 12225823
TI  - The a-wave latency in control subjects and patients with retinal diseases.
AB  - PURPOSE: To determine the a-wave latency of the electroretinograms (ERGs)
      recorded from control subjects and patients with retinal diseases. METHODS: The a
      wave latency and implicit time (IT) were measured retrospectively from the ERGs
      of 40 control subjects and 99 patients. The patients included 9 with complete
      congenital stationary night blindness (cCSNB), 13 with achromatopsia or cone
      dystrophy, 5 with supernormal and delayed rod ERG syndrome, and 72 with retinitis
      pigmentosa (RP). To assess whether latency measurements can be obtained reliably
      by different observers from patients with smaller a-wave amplitudes and noisier
      baselines, the a-wave latency and IT of the ERG of the right eye of 10 control
      subjects and 10 patients with RP were measured by three observers. RESULTS: The
      mean a-wave latency measured for the same 10 control ERGs by three observers
      differed by less than 1 millisecond while the mean IT differed by 1.7
      milliseconds. For 10 ERGs from RP patients, the mean for the a-wave latency
      measured by the three observers differed by less than 2.0 milliseconds and by 1.1
      millisecond for the IT. The coefficient of variation varied from 24.8% to 36.7%
      for the latency and from 11.5% to 16.0% for the IT. The a-wave latencies elicited
      by the 0-dB stimulus under scotopic and photopic conditions from the 40 control
      subjects were not statistically different. The a-wave latency in patients with
      cCSNB did not differ significantly from that in control subjects. The longer a
      wave latency in patients with achromatopsia suggested that the rods have a longer
      latency than cones. The scotopic and photopic a-wave latencies were significantly
      longer in RP patients. The longer latency in RP patients was not due to smaller a
      or b-wave amplitudes. CONCLUSIONS: The a-wave latency can be measured as
      reliably as the IT in control subjects but the reliability is not as good for the
      latency as for the IT in RP patients. The larger coefficients of variation in RP
      patients were most likely due to the measurements being made from RP patients at
      different stages of their disease. Our results suggest that the a-wave latency in
      control subjects is determined by cones under both scotopic and photopic
      conditions. The longer a-wave latency in RP patients suggests that the rods and
      cones are altered over a significant area of the retina.

PMID- 12225824
TI  - Multifocal electroretinograms in early primary open-angle glaucoma.
AB  - PURPOSE: To determine the utility of multifocal electroretinograms (mfERGs) in
      patients with early primary open-angle glaucoma (POAG) with unilateral visual
      field abnormalities. METHODS: mfERGs were recorded from 24 eyes of 12 cases of
      early POAG (stage I for 1 eye and stage II for the other eye on the Kosaki
      scale). The implicit times and amplitudes of the second-order kernel summed for
      the whole visual field, for the superior and inferior hemi-fields, and for
      quadrantic fields of the stage I and stage II eyes were compared. RESULTS:
      Neither the first- nor the second-order kernels of the mfERGs showed any changes
      reflecting glaucomatous visual field abnormalities. The implicit times and
      amplitudes of the second-order kernel summed for the whole visual field, the
      superior and inferior hemi-visual fields, and quadrantic visual fields of the
      stage I and stage II eyes were also not significantly different. CONCLUSIONS: We
      conclude that because the second-order kernel of the mfERG does not correlate
      with the visual field abnormality in early POAG, the second-order kernel of the
      mfERG that can be recorded at present is highly unlikely to reflect the function
      of the ganglion cells in the inner retinal layers.

PMID- 12225825
TI  - Ultrasound biomicroscopic findings in hallerman-streiff syndrome.
AB  - PURPOSE: To demonstrate the usefulness of ultrasound biomicroscopy in detecting
      the morphological changes in the lens caused by the spontaneous absorption of
      lens material and to detect fundus abnormalities in a patient with Hallermann
      Streiff syndrome. METHODS: Case report of an infant diagnosed at the age of 2
      months as having Hallermann-Streiff syndrome. RESULTS: Spontaneous lens
      absorption occurred during the course of follow-up and was detected only by
      ultrasound biomicroscopy after the patient was prepared for cataract surgery. The
      changes in the anterior chamber depth and lens shapes were documented by
      ultrasound biomicroscopy. Retinal folds that were barely observable by
      conventional ophthalmoscopy because of a dense cataract were clearly shown by
      ultrasound biomicroscopy. CONCLUSIONS: Ultrasound biomicroscopy can be used to
      examine the lenses of eyes that are not observable with conventional optical
      instruments. Ultrasound biomicroscopy can also be used to study the posterior
      segment of microphthalmic eyes. We recommend preoperative ultrasound
      biomicroscopy to prevent unnecessary anesthesia and surgical preparation.

PMID- 12225826
TI  - Vitrectomy combined with phacoemulsification and intraocular lens implantation
      for diabetic macular edema.
AB  - PURPOSE: The outcome of vitrectomy combined with phacoemulsification and
      intraocular lens implantation (PEA+IOL) for diabetic macular edema was evaluated.
      METHODS: Included in this study were 31 patients (42 eyes) with clinically
      significant diabetic macular edema, in whom posterior vitreous detachment was not
      observed. Pars plana vitrectomy combined with PEA+IOL was performed on 15 eyes.
      Sixteen phakic eyes and 11 pseudophakic eyes were followed up without vitrectomy
      as controls. Visual acuity and the state of macular edema were evaluated.
      RESULTS: After follow-up of 18 +/- 7 (mean +/- SD) months, clinically significant
      macular edema remained in 3 eyes (20%) of the vitrectomy group, in 11 eyes (69%)
      of the phakic control group, and in 9 eyes (82%) of the pseudophakic control
      group. The logarithm of the minimal angle of resolution (Log(MAR)) of the best
      corrected visual acuity of the vitrectomy group eyes significantly improved from
      1.09 +/- 0.27 to 0.80 +/- 0.35 (P <.01), while that of pseudophakic control eyes
      significantly decreased from 0.59 +/- 0.17 to 0.86 +/- 0.28 (P <.05). The
      Log(MAR) of phakic control eyes also decreased from 0.82 +/- 0.36 to 0.93 +/-
      0.30, but there was no significant difference (P =.19). CONCLUSION: Vitrectomy
      combined with PEA+IOL is an effective surgical modality to improve visual acuity
      in eyes with clinically significant diabetic macular edema.

PMID- 12225827
TI  - Retinal dystrophy in a Japanese boy harboring the mitochondrial DNA T8993G
      mutation.
AB  - BACKGROUND: Patients with the mitochondrial (mt) DNA T8993G mutation reportedly
      have variable neurologic manifestations. In these patients, retinal dystrophies
      progress from salt-and-pepper appearance to severe diffuse pigmentary
      retinopathy. CASE: A Japanese boy harboring the mtDNA T8993G mutation had
      hypotonia, ataxia, and developmental delay. His lactate values in serum and
      cerebrospinal fluid were elevated. Magnetic resonance imaging showed symmetrical
      areas of T2-weighted hyperintensity in the putamen and caudate. OBSERVATIONS: In
      ophthalmological examinations, his pupils reacted sluggishly to light. The
      patient had mottling of the retina without pigmentation and subnormal
      electroretinographic responses in both fundi. No ophthalmoparesis or nystagmus
      was observed. CONCLUSION: Retinal dystrophy without pigmentation was found in a
      Japanese boy diagnosed with the mtDNA T8993G mutation. This is believed to be the
      first report of retinal manifestations in Japanese patients with this mutation.

PMID- 12225828
TI  - Presumed choroidal atypical tuberculosis superinfected with cytomegalovirus
      retinitis in an acquired immunodeficiency syndrome patient: a case report.
AB  - BACKGROUND: To report an unusual case of multifocal choroidopathy with uveitis
      and cytomegalovirus (CMV) retinitis in a patient with acquired immunodeficiency
      syndrome (AIDS) after initially presenting with pulmonary tuberculosis
      (Mycobacterium kansasii). CASE: Slit-lamp biomicroscopy and indirect
      ophthalmoscopic examination were done. Vitreous biopsy, pars plana vitrectomy,
      and retinal biopsy were performed. Computer tomography scan, magnetic resonance
      imaging and biopsy of the brain were also carried out. OBSERVATIONS: Multiple
      yellowish-white, round, slightly elevated subretinal pigment epithelium lesions
      were noted in areas devoid of the atrophic retina of previous CMV infection.
      Anterior uveitis and vitritis were also noted. Vitreous, retina, and brain biopsy
      did not offer any clue for diagnosis. The visual acuity improved later, along
      with recovered immunity under the anti-tuberculosis medications and the cocktail
      therapy for AIDS. CONCLUSIONS: Combined CMV retinitis and atypical tuberculosis
      chorioretinitis, although rare, can develop in the patients with AIDS. Systemic
      dissemination of atypical tuberculosis infection should be responsible for the
      choroidopathy in this patient.

PMID- 12225829
TI  - An analysis of BIGH3 mutations in patients with corneal dystrophies in the Kyushu
      district of Japan.
AB  - PURPOSE: To assess the involvement of BIGH3 in corneal dystrophies (CD) with an
      autosomal dominant trait, in patients referred to a hospital in the Kyushu
      district of Japan. METHODS: Forty-five CD patients from 44 families were studied.
      Genomic DNA was extracted from peripheral blood, and exons 4 and 12 of the BIGH3
      gene were amplified by polymerase chain reaction followed by direct sequencing.
      RESULTS: In exon 4, an R124H mutation associated with Avellino corneal dystrophy
      (ACD) was found in 39/44 families (86.4%) and an R124C mutation associated with
      lattice corneal dystrophy type 1 (LCD1) was detected in 2/44 families (4.5%). In
      exon 12, an R555W mutation associated with granular corneal dystrophy (GCD) was
      detected in 4/44 families (9.1%). CONCLUSIONS: Codons R124 and R555 of the BIGH3
      gene represent mutational hotspots in the genomes of Japanese patients with
      autosomal-dominant CD.

PMID- 12225846
TI  - Highly efficient over-production in E. coli of YvcC, a multidrug-like ATP-binding
      cassette transporter from Bacillus subtilis.
AB  - ATP-binding cassette (ABC) transporters have often been refractory to over
      expression. Using the C41(DE3) E. coli as a host strain, membrane vesicles highly
      enriched (>50%) in YvcC, a previously uncharacterized ABC transporter from
      Bacillus subtilis homologous to P-glycoprotein multidrug transporters, were
      obtained. The functionality of YvcC was assessed by its high vanadate-sensitive
      ATPase activity and its ability to transport a fluorescent drug, the Hoechst
      33342.

PMID- 12225847
TI  - Use of peptide antibodies to probe for the mitoxantrone resistance-associated
      protein MXR/BCRP/ABCP/ABCG2.
AB  - Recent studies have characterized the ABC half-transporter associated with
      mitoxantrone resistance in human cancer cell lines. Encoded by the ABCG2 gene,
      overexpression confers resistance to camptothecins, as well as to mitoxantrone.
      We developed four polyclonal antibodies against peptides corresponding to four
      different epitopes on the mitoxantrone resistance-associated protein, ABCG2.
      Three epitopes localized on the cytoplasmic region of ABCG2 gave rise to high
      affinity antibodies, which were demonstrated to be specific for ABCG2. Western
      blot analysis of cells with high levels of ABCG2 showed a single major band of
      the expected 72-kDa molecular size of ABCG2 under denaturing conditions.
      Immunoblot analysis performed under non-reducing conditions and after treatment
      with cross-linking reagents demonstrated a molecular weight shift from 72 kDa to
      several bands of 180 kDa and higher molecular weight, suggesting detection of
      dimerization products of ABCG2. Evidence of N-linked glycosylation was also
      obtained using tunicamycin and N-glycosidase F. Finally, both by light,
      fluorescence and electron microscopic immunohistochemical staining, we
      demonstrate cytoplasmic and predominantly plasma membrane localization of ABCG2
      in cell lines with high levels of expression. Plasma membrane staining was
      observed on the surface of the chorionic villi in placenta. These results support
      the hypothesis that ABCG2 is an ABC half-transporter that forms dimers in the
      plasma membrane, functioning as an ATP-dependent outward pump for substrate
      transport.

PMID- 12225848
TI  - No evidence for inhibition of ENaC through CFTR-mediated release of ATP.
AB  - Both purinergic stimulation and activation of cystic fibrosis transmembrane
      conductance regulator (CFTR) increases Cl(-) secretion and inhibit amiloride
      sensitive Na(+) transport. CFTR has been suggested to conduct adenosine 5'
      triphosphate (ATP) or to control ATP release to the luminal side of epithelial
      tissues. Therefore, a possible mechanism on how CFTR controls the activity of
      epithelial Na(+) channels (ENaC) could be by release of ATP or uridine 5'
      triphosphate (UTP), which would then bind to P2Y receptors and inhibit ENaC. We
      examined this question in native tissues from airways and colon and in Xenopus
      oocytes. Inhibition of amiloride-sensitive transport by both CFTR and
      extracellular nucleotides was observed in colon and trachea. However, nucleotides
      did not inhibit ENaC in Xenopus oocytes, even after coexpression of P2Y(2)
      receptors. Using different tools such as hexokinase, the P2Y inhibitor suramin or
      the Cl(-) channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid
      (DIDS), we did not detect any role of a putative ATP secretion in activation of
      Cl(-) transport or inhibition of amiloride sensitive short circuit currents by
      CFTR. In addition, N(2),2'-O-dibutyrylguanosine 3',5'-cyclic monophosphate (cGMP)
      and protein kinase G (PKG)-dependent phosphorylation or the nucleoside
      diphosphate kinase (NDPK) do not seem to play a role for the inhibition of ENaC
      by CFTR, which, however, requires the presence of extracellular Cl(-).

PMID- 12225849
TI  - Brownian dynamics simulation of the unsaturated lipidic molecules oleic and
      docosahexaenoic acid confined in a cellular membrane.
AB  - A Brownian dynamics (BD) simulation of two unsaturated molecules, oleic and
      docosahexaenoic acid, in an environment that reproduces a cellular membrane, is
      presented. The results of the simulations, performed using mean-field potentials,
      were calibrated with experimental results obtained for oleic acid in a cellular
      membrane. The agreement between simulation and experimental results is excellent
      which validates subsequent simulation outcome for docosahexaenoic acid. This
      molecule is a major component of several cellular membranes thought to be
      involved in specific biological functions that require conformational changes of
      membrane components. The results for docosahexaenoic acid indicate that it is
      minimally influenced by temperature changes and that it presents great
      conformational variability.

PMID- 12225850
TI  - The yeast SR protein kinase Sky1p modulates salt tolerance, membrane potential
      and the Trk1,2 potassium transporter.
AB  - Protein kinases dedicated to the phosphorylation of SR proteins have been
      implicated in the processing and nuclear export of mRNAs. Here we demonstrate in
      Saccharomyces cerevisiae their participation in cation homeostasis. A null mutant
      of the single yeast SR protein kinase Sky1p is viable but exhibits increased
      tolerance to diverse toxic cations such as Na(+), Li(+), spermine,
      tetramethylammonium, hygromycin B and Mn(2+). This pleiotropic phenotype
      correlates with reduced accumulation of cations, suggesting a decrease in
      membrane electrical potential. Genetic analysis and Rb(+) uptake measurements
      indicate that Sky1p modulates Trk1,2, the high-affinity K(+) uptake system of
      yeast and a major determinant of membrane potential.

PMID- 12225851
TI  - Formation of transition metal-doxorubicin complexes inside liposomes.
AB  - Doxorubicin complexation with the transition metal manganese (Mn(2+)) has been
      characterized, differentiating between the formation of a doxorubicin-metal
      complex and doxorubicin fibrous-bundle aggregates typically generated following
      ion gradient-based loading procedures that rely on liposome encapsulated citrate
      or sulfate salts. The physical and chemical characteristics of the encapsulated
      drug were assessed using cryo-electron microscopy, circular dichroism (CD) and
      absorbance spectrophotometric analysis. In addition, in vitro and in vivo drug
      loading and release characteristics of the liposomal formulations were
      investigated. Finally, the internal pH after drug loading was measured with the
      aim of linking formation of the Mn(2+) complex to the presence or absence of a
      transmembrane pH gradient. Doxorubicin was encapsulated into either 1,2
      dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/cholesterol (Chol) or 1,2
      distearoyl-sn-glycero-3-phosphocholine (DSPC)/Chol liposomes, where the entrapped
      salts were citrate, MnSO(4) or MnCl(2). In response to a pH gradient or a Mn(2+)
      ion gradient, doxorubicin accumulated inside to achieve a drug-to-lipid ratio of
      approximately 0.2:1 (wt/wt). Absorbance and CD spectra of doxorubicin in the
      presence of Mn(2+) suggested that there are two distinct structures captured
      within the liposomes. In the absence of added ionophore A23187, drug loading is
      initiated on the basis of an established pH gradient; however, efficient drug
      uptake is not dependent on maintenance of the pH gradient. Drug release from
      DMPC/Chol is comparable regardless of whether doxorubicin is entrapped as a
      citrate-based aggregate or a Mn(2+) complex. However, in vivo drug release from
      DSPC/Chol liposomes indicate less than 5% or greater than 50% drug loss over a 24
      h time course when the drug was encapsulated as an aggregate or a Mn(2+) complex,
      respectively. These studies define a method for entrapping drugs possessing
      coordination sites capable of complexing transition metals and suggest that drug
      release is dependent on lipid composition, internal pH, as well as the nature of
      the crystalline precipitate, which forms following encapsulation.

PMID- 12225852
TI  - Permeability properties of apical and basolateral membranes of the guinea pig
      caecal and colonic epithelia for short-chain fatty acids.
AB  - Unidirectional fluxes of short-chain fatty acids (SCFA) indicated marked
      segmental differences in the permeability of apical and basolateral membranes.
      The aim of our study was to prove these differences in membrane permeability for
      a lipid-soluble substance and to understand the factors affecting these
      differences. Apical and basolateral membrane fractions from guinea pig caecal and
      colonic epithelia were isolated. Membrane compositions were determined and the
      permeability of membrane vesicles for the protonated SCFA was measured in a
      stopped-flow device. Native vesicles from apical membranes of the caecum and
      proximal colon have a much lower permeability than the corresponding vesicles
      from the basolateral membranes. For the distal colon, membrane permeabilities of
      native apical and basolateral vesicles are similar. In vesicles prepared from
      lipid extracts, the permeabilities for the protonated SCFA are negatively
      correlated to cholesterol content, whereas no such correlation was observed in
      native vesicles. Our findings confirm that the apical membrane in the caecum and
      proximal colon of guinea pig is an effective barrier against a rapid diffusion of
      small lipid-soluble substances such as SCFAH. Besides cholesterol and membrane
      proteins, there are further factors that contribute to this barrier property.

PMID- 12225853
TI  - Large-scale purification, dissociation and functional reassembly of the maltose
      ATP-binding cassette transporter (MalFGK(2)) of Salmonella typhimurium.
AB  - The maltose ATP-binding cassette (ABC) transporter of Salmonella typhimurium is
      composed of a membrane-associated complex (MalFGK(2)) and a periplasmic substrate
      binding protein. To further elucidate protein-protein interactions between the
      subunits, we have studied the dissociation and reassembly of the MalFGK(2)
      complex at the level of purified components in proteoliposomes. First, we
      optimized the yield in purified complex protein by taking advantage of a newly
      constructed expression plasmid that carries the malK, malF and malG genes in
      tandem orientation. Incorporated in proteoliposomes, the complex exhibited
      maltose binding protein/maltose-dependent ATPase activity with a V(max) of 1.25
      micromol P(i)/min/mg and a K(m) of 0.1 mM. ATPase activity was sensitive to
      vanadate and enzyme IIA(Glc), a component of the enterobacterial glucose
      transport system. The proteoliposomes displayed maltose transport activity with
      an initial rate of 61 nmol/min/mg. Treatment of proteoliposomes with 6.6 M urea
      resulted in the release of medium-exposed MalK subunits concomitant with the
      complete loss of ATPase activity. By adding increasing amounts of purified MalK
      to urea-treated proteoliposomes, about 50% of vanadate-sensitive ATPase activity
      relative to the control could be recovered. Furthermore, the phenotype of
      MalKQ140K that exhibits ATPase activity in solution but not when associated with
      MalFG was confirmed by reassembly with MalK-depleted proteoliposomes.

PMID- 12225854
TI  - Cloning and characterization of an aromatic amino acid and leucine permease of
      Penicillium chrysogenum.
AB  - The gene encoding the amino acid permease ArlP (Aromatic and leucine Permease)
      was isolated from the filamentous fungus Penicillium chrysogenum after PCR using
      degenerated oligonucleotides based on conserved regions of fungal amino acid
      permeases. The cDNA clone was used for expression of the permease in
      Saccharomyces cerevisiae M4054, which is defective in the general amino acid
      permease Gap1. Upon overexpression, an increase in the uptake of L-tyrosine, L
      phenylalanine, L-tryptophan and L-leucine was observed. Further competition
      experiments indicate that ArlP recognizes neutral and aromatic amino acids with
      an unbranched beta-carbon atom.

PMID- 12225855
TI  - Long-range effects on the binding of the influenza HA to receptors are mediated
      by changes in the stability of a metastable HA conformation.
AB  - X-ray studies show that influenza hemagglutinin (HA) forms an elongated structure
      connecting the influenza virus at one end to cell-surface receptors at the other.
      At neutral pH, the 20 N-terminal residues of HA2-referred to as the fusion
      peptide-are buried in a hydrophobic pocket, about 100 A away from the receptor
      binding site, and thus seem unlikely to affect HA binding to the receptor. To
      test this assumption, we mutated residues in the fusion peptide, heterologically
      expressed the mutated proteins in COS7 cells, and examined their ability to bind
      fluorescently labeled red blood cells (RBCs). Surprisingly, a significantly
      reduced binding was recorded for some of the mutants. Ample experimental data
      indicate that HA has at least two forms: the native structure at neutral pH (N)
      that is metastable and the fusogenic form (F), observed at low pH, which is
      stable. Thus, a simple interpretation of our data is that HA can bind to its
      receptors at the RBC surface in the N form much more effectively than in the F
      (or in any other stable) form and that the altered binding properties are due to
      destabilizing effects of the mutations on the N form. That is, some of the
      mutations involve reduction in the free energy barrier between the N and F forms.
      This, in turn, leads to reduction in the population of the N form, which is the
      only form capable of binding to the cell-surface receptors. To explore this
      possibility, we estimated the stability free energy difference between HA wild
      type (wt) and mutants in the N form using an empirical surface tension
      coefficient. The calculated stability differences correlated well with the
      measured binding, supporting the above interpretation. Our results are examined
      taking into account the available experimental data on the affinity of different
      soluble and membrane-attached forms of HA to its receptors.

PMID- 12225856
TI  - Unique assignment of inter-subunit association in GABA(A) alpha 1 beta 3 gamma 2
      receptors determined by molecular modeling.
AB  - Recent publications defined requirements for inter-subunit contacts in a
      benzodiazepine-sensitive GABA(A) receptor (GABA(A)R alpha 1 beta 3 gamma 2).
      There is strong evidence that the heteropentameric receptor contains two alpha 1,
      two beta 3, and one gamma 2 subunit. However, the available data do not
      distinguish two possibilities: When viewed clockwise from an extracellular
      viewpoint the subunits could be arranged in either gamma 2 beta 3 alpha 1 beta 3
      alpha 1 or gamma 2 alpha 1 beta 3 alpha 1 beta 3 configurations. Here we use
      molecular modeling to thread the relevant GABA(A)R subunit sequences onto a
      template of homopentameric subunits in the crystal structure of the acetylcholine
      binding protein (AChBP). The GABA(A) sequences are known to have 15-18% identity
      with the acetylcholine binding protein and nearly all residues that are conserved
      within the nAChR family are present in AChBP. The correctly aligned GABA(A)
      sequences were threaded onto the AChBP template in the gamma 2 beta 3 alpha 1
      beta 3 alpha 1 or gamma 2 alpha 1 beta 3 alpha 1 beta 3 arrangements. Only the
      gamma 2 alpha 1 beta 3 alpha 1 beta 3 arrangement satisfied three known criteria:
      (1) alpha 1 His(102) binds at the gamma 2 subunit interface in proximity to gamma
      2 residues Thr(142), Phe(77), and Met(130); (2) alpha 1 residues 80-100 bind near
      gamma 2 residues 91-104; and (3) alpha 1 residues 58-67 bind near the beta 3
      subunit interface. In addition to predicting the most likely inter-subunit
      arrangement, the model predicts which residues form the GABA and benzodiazepine
      binding sites.

PMID- 12225857
TI  - Residue-specific millisecond to microsecond fluctuations in bacteriorhodopsin
      induced by disrupted or disorganized two-dimensional crystalline lattice, through
      modified lipid-helix and helix-helix interactions, as revealed by 13C NMR.
AB  - We have recorded 13C NMR spectra of [3-13C]-, [1-13C]Ala-, and [1-13C]Val-labeled
      bacteriorhodopsin (bR), W80L and W12L mutants and bacterio-opsin (bO) from
      retinal-deficient E1001 strain, in order to examine the possibility of their
      millisecond to microsecond local fluctuations with correlation time in the order
      of 10(-4) to 10(-5) s, induced or prevented by disruption or assembly of two
      dimensional (2D) crystalline lattice, respectively, at ambient temperature. The
      presence of disrupted or disorganized 2D lattice for W12L, W80L and bO from E1001
      strain was readily visualized by increased relative proportions of surrounding
      lipids per protein, together with their broadened 13C NMR signals of
      transmembrane alpha-helices and loops in [3-13C]Ala-labeled proteins, with
      reference to those of wild-type. In contrast, 13C CP-MAS NMR spectra of [1
      13C]Ala- and Val-labeled these mutants were almost completely suppressed, owing
      to the presence of fluctuations with time scale of 10(-4) s interfered with magic
      angle spinning. In particular, 13C NMR signals of [1-13C]Ala-labeled
      transmembrane alpha-helices of wild-type were almost completely suppressed at the
      interface between the surface and inner part (up to 8.7 A deep from the surface)
      with reference to those of the similarly suppressed peaks by Mn(2+)-induced
      accelerated spin-spin relaxation rate. Such fluctuation-induced suppression of
      13C NMR peaks from the interfacial regions, however, was less significant for [1
      13C]Val-labeled proteins, because fluctuation motions in Val residues with bulky
      side-chains at the C(alpha) moiety were modified to those of longer correlation
      time (>10(-4) s), if any, by residue-specific manner. To support this view, we
      found that such suppressed 13C NMR signals of [1-13C]Ala-labeled peaks in the
      wild-type were recovered for D85N and bO in which correlation times of
      fluctuations were shifted to the order of 10(-5) s due to modified helix-helix
      interactions as previously pointed out [Biochemistry, 39 (2000) 14472; J.
      Biochem. (Tokyo) 127 (2000) 861].

PMID- 12225858
TI  - Electric field-induced orientation of L- and DL-phosphatidylcholine bilayers.
AB  - Membrane orientation induced by an alternating electric field has been examined
      for the L-enantiomer and racemic dipalmitoylphosphatidylcholine (DPPC) bilayers.
      The orientation effect was measured by bending curvature of hairpin-like
      deformation of the multilamellar cylindrical tubes with varying field-strength,
      frequency and tube size. It has been observed that both L- and DL-DPPC tubes are
      similar in the profiles of field-strength dependence and frequency dependence on
      the curvature deformation, but different in the deformed curvatures. DL-DPPC
      tubes deform largely as compared with L-DPPC tubes. The square of the deformed
      curvature of DL-DPPC tubes is larger than that of L-DPPC by about 37% on average.
      The result indicates that the racemic membrane is responsive to the electric
      field as compared with the L-enantiomer membrane. This suggests that a hybrid
      arrangement of head groups of the racemic lipid leads an effective response of
      the membrane due to the head group orientation.

PMID- 12225859
TI  - Characterization of the system L amino acid transporter in T24 human bladder
      carcinoma cells.
AB  - System L is a major nutrient transport system responsible for the Na(+)
      independent transport of large neutral amino acids including several essential
      amino acids. In malignant tumors, a system L transporter L-type amino acid
      transporter 1 (LAT1) is up-regulated to support tumor cell growth. LAT1 is also
      essential for the permeation of amino acids and amino acid-related drugs through
      the blood-brain barrier. To search for in vitro assay systems to examine the
      interaction of chemical compounds with LAT1, we have investigated the expression
      of system L transporters and the properties of [14C]L-leucine transport in T24
      human bladder carcinoma cells. Northern blot, real-time quantitative PCR and
      immunofluorescence analyses have reveled that T24 cells express LAT1 in the
      plasma membrane together with its associating protein 4F2hc, whereas T24 cells do
      not express the other system L isoform LAT2. The uptake of [14C]L-leucine by T24
      cells is Na(+)-independent and almost completely inhibited by system L selective
      inhibitor BCH. The profiles of the inhibition of [14C]L-leucine uptake by amino
      acids and amino acid-related compounds in T24 cells are comparable with those for
      the LAT1 expressed in Xenopus oocytes. The majority of [14C]L-leucine uptake is,
      therefore, mediated by LAT1 in T24 cells. Consistent with LAT1 in Xenopus
      oocytes, the efflux of preloaded [14C]L-leucine is induced by extracellularly
      applied substrates of LAT1 in T24 cells. This efflux measurement has been proven
      to be more sensitive than that in Xenopus oocytes, because triiodothyronine,
      thyroxine and melphalan were able to induce the efflux of preloaded [14C]L
      leucine in T24 cells, which was not detected for Xenopus oocyte expression
      system. T24 cell is, therefore, proposed to be an excellent tool to examine the
      interaction of chemical compounds with LAT1.

PMID- 12225860
TI  - Use of laurdan fluorescence intensity and polarization to distinguish between
      changes in membrane fluidity and phospholipid order.
AB  - Laurdan is a fluorescent probe that detects changes in membrane phase properties
      through its sensitivity to the polarity of its environment in the bilayer.
      Variations in membrane water content cause shifts in the laurdan emission
      spectrum, which are quantified by calculating the generalized polarization (GP).
      We tested whether laurdan fluorescence could be used to distinguish differences
      in phospholipid order from changes in membrane fluidity by examining the
      temperature dependence of laurdan GP and fluorescence anisotropy in
      dipalmitoylphosphatidylcholine (DPPC) vesicles. The phase transition from the
      solid ordered phase to the liquid disordered phase was observed as a decrease in
      laurdan GP values from 0.7 to -0.14 and a reduction in anisotropy from 0.25 to
      0.12. Inclusion of various amounts of cholesterol in the membranes to generate a
      liquid ordered phase caused an increase in the apparent melting temperature
      detected by laurdan GP. In contrast, cholesterol decreased the apparent melting
      temperature estimated from anisotropy measurements. Based on these results, it
      appeared that laurdan anisotropy detected changes in membrane fluidity while
      laurdan GP sensed changes in phospholipid order. Thus, the same fluorescent probe
      can be used to distinguish effects of perturbations on membrane order and
      fluidity by comparing the results of fluorescence emission and anisotropy
      measurements.

PMID- 12225861
TI  - Triggered release of doxorubicin following mixing of cationic and anionic
      liposomes.
AB  - In many applications, an ability of liposomes to retain drug and then rapidly
      release it at some later time would be of benefit. In this work, we investigate
      the ability of cationic large unilamellar vesicles (LUV) to promote rapid release
      of doxorubicin from anionic LUV. It is shown that the addition of cationic
      liposomes containing cholesterol, dioleoylphosphatidylethanolamine (DOPE),
      distearoylphosphatidylcholine (DSPC) and the cationic lipid N,N-dioleyl-N,N
      dimethylammonium chloride (DODAC) to doxorubicin-containing LUV composed of
      cholesterol, DOPE, DSPC and the anionic lipid dioleoyphosphatidylglycerol (DOPG)
      can result in release of more than 90% of the drug in times of 30 s or less.
      Further, it is shown that these release characteristics are exquisitely dependent
      on the presence of DOPE and cholesterol. In the absence of DOPE, much slower
      release rates are observed, with maximum release levels of 50% after a 2-h
      incubation at 20 degrees C. Remarkably, threshold levels of more than 10 mol%
      cholesterol are required before any appreciable release is observed. [31P]NMR
      spectroscopy and freeze-fracture electron microscopy studies reveal that systems
      giving rise to rapid release of doxorubicin exhibit limited formation of inverted
      hexagonal (H(II)) phase, suggesting that these lipids facilitate drug release by
      formation of local regions of non-bilayer structure. It is concluded that drug
      release triggered by mixing anionic and cationic liposomes could be of utility in
      drug delivery applications.

PMID- 12225862
TI  - Complete replacement of basic amino acid residues with cysteines in Rickettsia
      prowazekii ATP/ADP translocase.
AB  - The ATP/ADP translocase (Tlc) of Rickettsia prowazekii is a basic protein with
      isoelectric point (pI)=9.84. It is conceivable, therefore, that basic residues in
      this protein are involved in electrostatic interactions with negatively charged
      substrates. We tested this hypothesis by individually mutating all basic residues
      in Tlc to Cys. Unexpectedly, mutations of only 20 out of 51 basic residues
      resulted in greater than 80% inhibition of transport activity. Moreover, 12 of
      51Cys-substitution mutants exhibited higher than wild-type (WT) activity. At
      least in one case this up-effect was additive and the double mutant Lys422Cys
      Lys427Cys transported ATP five-fold better than WT protein. Since in these two
      single mutants and in the corresponding double mutant K(m)'s were similar to that
      of WT protein, we conclude that Tlc may have evolved a mechanism that limits the
      transporter's exchange rate and that at least these two basic residues play a key
      role in that mechanism. Based on the alignment of 16 Tlc homologs, the loss of
      activity in the mutants poorly correlates with charge conservation within the Tlc
      family. Also, despite the presence of three positively charged and one negatively
      charged intramembrane residues, we have failed to identify potential charge pairs
      (salt bridges) by either charge reversal or charge neutralization approaches.

PMID- 12225863
TI  - Expression of Nogo protein by growing axons in the developing nervous system.
AB  - We produced monoclonal antibody NG1 that strongly binds growing axons in the
      developing nervous system of mice. This antibody intensely labeled the growth
      cone of cultured neurons. Although these immunostaining patterns suggested the
      association of growing axons with the antigen recognized by this antibody, the
      antigen was identified as Nogo protein, an axonal repulsive factor isolated from
      the myelin. On the basis of this unexpected finding, we discuss the possible
      functions of Nogo in the developing nervous system.

PMID- 12225864
TI  - Expression of glutamate transporters and ionotropic glutamate receptors in GLAST
      knockout mice.
AB  - In order to investigate the molecular mechanism underlying high seizure
      susceptibility of GLAST knockout mice, we carried out Western blotting for the
      expression of GLT-1, EAAC-1, and several kinds of glutamate receptors in the
      hippocampus and the cortex. Although no significant difference was observed
      between GLAST (+/+) and (-/-) mice in terms of expression of GLT-1 and EAAC-1 in
      the hippocampus, these proteins were over-expressed in the frontal cortex in
      GLAST (-/-) mice (GLT-1, about 210% increase; EAAC-1, about 180% increase).
      Expression of hippocampal Glu-R1 and Glu-R2 in GLAST (-/-) mice was remarkably
      increased (Glu-R1, about 140% increase; Glu-R2, about 160% increase), while Glu
      R3 and NMDA receptors levels (NMDA-R1, 2A and 2B) were equal to those in control.
      Cortical levels of Glu-R1, -R2 and -R3 receptors in GLAST (-/-) mice were
      remarkably decreased (Glu-R1, about 60% decrease; Glu-R2, about 60% decrease; Glu
      R3, about 70% decrease), while NMDA receptors were remarkably increased in
      comparison to those in GLAST (+/+) mice (N-R1, about 150% increase; N-R2A, about
      150% increase; N-R2B, about 140% increase). These data suggest that the increased
      susceptibility to seizures in GLAST (-/-) mice might be derived from increased
      expression of Glu-R1 in the hippocampus coupled with decreased cortical
      expression of Glu-R2 and increased NMDA-R1 and -2A, -2B expression.

PMID- 12225865
TI  - The 3' untranslated region of the new rat synaptic vesicle protein 2B mRNA
      transcript inhibits translational efficiency.
AB  - Post-transcriptional regulatory mechanisms have been shown to play a major role
      in gene expression in eukaryotic cells. Sequences within the 3'-untranslated
      region (3'UTR) of mRNAs have been described as being important for enhancing or
      inhibiting message translation. Using fluorescence microscopy, Western blotting
      and the reverse transcription-polymerase chain reaction (RT-PCR) method, we
      demonstrate that the 3'UTR of the new rat transcript of synaptic vesicle protein
      2B (SV2Bb) mRNA is involved in post-transcriptional regulation of SV2Bb
      translation. When fused to a reporter gene, this 3'UTR markedly inhibited protein
      synthesis in transiently transfected cells and this decreased translational
      efficiency did not occur through changes in mRNA stability. In conclusion, our
      study gives new insights into unraveling the molecular mechanisms involved in the
      post-transcriptional regulation of the SV2B gene.

PMID- 12225866
TI  - Diurnal changes in arginine vasopressin gene transcription in the rat
      suprachiasmatic nucleus.
AB  - The diurnal changes in arginine vasopressin (AVP) mRNA and heteronuclear (hn)
      RNA, an indicator for gene transcription, were examined in the hypothalamus of
      Sprague-Dawley rats using in situ hybridization. AVP hnRNA levels in the
      suprachiasmatic nucleus (SCN) varied during a 24-h cycle and showed a peak at day
      time [Zeitgeber time (ZT) 5], which preceded the peak in AVP mRNA levels by 4 h.
      AVP hnRNA was undetectable at ZT 13 and 17, indicating that the gene
      transcription was almost shut down at these time points. AVP mRNA levels in the
      SCN continued to decrease at night (ZT 13, 17 and 21) when there were minimal
      changes in transcription, suggesting rapid turnover of mRNA. Similar diurnal
      changes in AVP hnRNA levels were observed without photic cues. On the other hand,
      AVP hnRNA or mRNA levels in the supraoptic nucleus, where AVP is synthesized in
      response to plasma osmolarity and/or volume, did not show any circadian rhythm.
      These data suggest that both dynamic changes in AVP gene transcription and rapid
      turnover of mRNA contribute to the diurnal variation in AVP mRNA levels in the
      SCN.

PMID- 12225867
TI  - Expression of VPAC2 receptor and PAC1 receptor splice variants in the trigeminal
      ganglion of the adult rat.
AB  - PACAP and VIP are members of the VIP/secretin/glucagon family of peptides with
      neurotransmitter, neuroprotective, and neurotrophic functions. PACAP and VIP are
      known to be upregulated in primary sensory neurons following nerve injury,
      implying that these neuropeptides could be mediators of sensory transmission in
      neuropathic pain states. Nerve injury at the level of the trigeminal root is
      thought to be the prime cause of trigeminal neuralgia. Since cross-excitation (a
      chemically-mediated form of nonsynaptic transmission) within the TG is postulated
      to play a central role in trigeminal neuralgia, we studied the expression of
      PACAP and VIP receptors in the TG by RT PCR and immunocytochemistry. Of the three
      known receptors (PAC1, VPAC1 and VPAC2), RT PCR revealed the presence of mRNA for
      VPAC2 and several splice variants of the PAC1 receptor. Immunocytochemistry
      showed PAC1 and VPAC2 to be present in small-diameter TG neurons. Thus, PACAP and
      VIP are potential mediators of cross-excitation in the TG.

PMID- 12225868
TI  - Mild stress sensitizes the brain's response to morphine.
AB  - Behavioral experiments demonstrate that stress alters the individual's attitude
      towards opiates. In search for the underlying neuronal mechanisms we investigated
      the influence of stress on morphine-induced c-fos expression in the brain, and,
      vice versa, the influence of morphine application on the brain's c-fos response
      to stress. In our experiments, mild stress was induced either by brief
      immobilization (1 min) or by exposing the rats to a noisy and unfamiliar
      environment. These kinds of stress, unlike severe stress, did not elicit c-fos
      expression in the paraventricular nucleus of the hypothalamus. However, c-fos
      expression was observed in the lateral septum, medial striatum, claustrum and in
      the cingulate and piriform cortices under these conditions. The stress-induced c
      fos induction was markedly decreased by a moderate (10 mg/kg) dose of morphine.
      On the other hand, morphine alone (50 mg/kg) caused only a weak c-fos expression
      in nai;ve animals despite of the rather high dose. If, however, this morphine
      dose was applied in the presence of a stressful stimulus, a pronounced c-fos
      expression in the dorsal striatum resulted. This c-fos signal was comparable with
      the signal seen in morphine-sensitized animals. Thus, distressing conditions seem
      to alter the brain's response to morphine at the level of gene expression, and
      this could be important for initiating voluntary opiate intake.

PMID- 12225869
TI  - Altered expression of novel genes in the cerebral cortex following experimental
      brain injury.
AB  - Damage to the cerebral cortex results in neurological impairments such as motor,
      attention, memory and executive dysfunctions. To examine the molecular mechanisms
      contributing to these deficits, mRNA expression was profiled using high-density
      cDNA microarray hybridization after experimental cortical impact injury in mice.
      The mRNA levels at 2 h, 6 h, 24 h, 3 days and 14 days after injury were compared
      with those of control animals. This revealed 86 annotated genes and 24 expression
      sequence tags (ESTs) as being differentially expressed with a 1.5-fold or greater
      change. Quantitative real-time PCR analysis was used to independently verify
      these results for selected genes. Seven functional classes of genes were found to
      be altered following injury, including transcription factors, signal transduction
      genes and inflammatory proteins. While a few of these genes have been previously
      reported to be differentially regulated following injury, the most of the genes
      have not been previously implicated in traumatic brain injury (TBI)
      pathophysiology. For example, consistent with previous reports, the transcription
      factor c-jun and the neurotrophic factor bdnf mRNA levels were altered as a
      result of TBI. Among the novel genes, the mRNA levels for the high mobility group
      protein 1 (hmg-1), the regulator of G-protein signaling 2 (rgs-2), the
      transforming growth factor beta inducible early growth response (tieg), the
      inhibitor of DNA binding 3 (id3), and the heterogeneous nuclear ribonucleoprotein
      H (hnrnp h) were changed following injury. The functional significance of these
      genes in neurite outgrowth, neuronal regeneration, and plasticity following
      injury are discussed.

PMID- 12225870
TI  - Cyclooxygenase-2 modulates brain inflammation-related gene expression in central
      nervous system radiation injury.
AB  - Although the contribution of cyclooxygenase-2 (COX-2) to peripheral inflammation
      is well documented, little is known about its role in brain inflammation. For
      this purpose we studied COX-2 expression in the mouse brain following ionizing
      radiation in vivo, as well as in murine glial cell cultures in vitro. The
      possible role of COX-2 in modulating brain inflammation was examined utilizing NS
      398, a COX-2 selective inhibitor. Our results indicate that COX-2 is
      significantly induced in astrocyte and microglial cultures by radiation injury as
      well as in brain. Increased levels of prostaglandin E(2) in irradiated brain were
      reduced by NS-398. Moreover, NS-398 administration significantly attenuated
      levels of induction for the majority of inflammatory mediators examined,
      including TNFalpha, IL-1beta, IL-6, iNOS, ICAM-1, and MMP-9. In contrast, the
      chemokines MIP-2 and MCP-1 showed enhanced levels of induction following NS-398
      administration. These results indicate that COX-2 modulates the inflammatory
      response in brain following radiation injury, and suggest the use of COX-2
      selective inhibitors for the management of CNS inflammation.

PMID- 12225871
TI  - Plasminogen mRNA induction in the mouse brain after kainate excitation:
      codistribution with plasminogen activator inhibitor-2 (PAI-2) mRNA.
AB  - Plasminogen (Plg), which can be converted to the active protease plasmin by
      plasminogen activators, has been previously implicated in brain plasticity and in
      toxicity inflicted in hippocampal pyramidal neurons by kainate. Here we have
      localized Plg. mRNA through in situ hybridization in brain cryosections derived
      from normal adult mice or after kainate injection (i.p.). The results indicated
      that Plg mRNA was undetectable in the normal brain, but after kainate injection
      it was induced in neuronal cells in multiple, but specific areas, including
      layers II-III of the neocortex; the olfactory bulb, anterior olfactory nucleus,
      and the piriform cortex; the caudate/putamen and accumbens nucleus shell;
      throughout the amygdaloid complex; and in the CAI/CA3 subfields of the
      hippocampus. Interestingly, this distribution pattern coincided with what we have
      recently described for the plasminogen activator inhibitor-2 (PAI-2) mRNA,
      however differing from that of the plasminogen activator inhibitor-1 (PAI-1)
      mRNA, as also shown here. These results suggest that enhanced Plg gene expression
      could be involved in events associated with olfactory, striatal, and limbic
      structures. Furthermore, because PAI-2 is thought to intracellularly counteract
      cytotoxic events, our results raise the possibility that PAI-2 can act in the
      brain as an intracellular neuroprotector against potential plasmin-mediated
      toxicity.

PMID- 12225872
TI  - Synexpression analysis of ESTs in the rat brain reveals distinct patterns and
      potential drug targets.
AB  - The gene expression profiles of 146 novel ESTs were characterized in newborn and
      adult rat brains via radioactive in situ hybridization. Using Euclidean metrics
      and hierarchical clustering tools the brain expression profiles obtained
      clustered into seven synexpression groups. The groups were: I, non-detectable
      expression (68 ESTs); II, low expression in hippocampus (40 ESTs); III, low
      expression in adult, high expression in newborn (two ESTs); IV, medium expression
      throughout brain (31 ESTs); V, high expression throughout brain (three ESTs); VI,
      selective high expression in hippocampus, caudate and putamen (one EST); VII,
      selective high expression in hippocampus (one EST). Five ESTs were expressed in
      the striatum and three responded transcriptionally to neuroleptic and
      neuroprotective drug treatments, suggesting that this approach could be used to
      detect novel drug targets. These results provide a useful starting point to
      explore the functional genomics of genes without known functions forthcoming from
      various genome projects.

PMID- 12225873
TI  - Differential promoter usage of mouse mu-opioid receptor gene during development.
AB  - Previously, we demonstrated that mouse mu-opioid receptor (MOR) gene expression
      is regulated by both distal and proximal promoters, with the latter playing a
      major role in controlling MOR transcription in the adult mouse brain. Here, we
      report studies of the relative usages of the mouse MOR dual promoters during
      murine development. We used the reverse transcription-polymerase chain reaction
      (RT-PCR) method, which gave results similar to those using binding assays or in
      situ hybridization. However, due to the greater sensitivity of RT-PCR method, we
      were able to detect the emergence of MOR as early as at embryonic day 8.5 (E8.5).
      We found that both proximal and distal promoters were active at E8.5. The
      proximal promoter initiated approximately two-thirds of total MOR transcripts at
      E8.5, with the distal promoter directing transcription of the remaining one
      third. This is the greatest relative contribution of the distal promoter to MOR
      transcription we have observed during any time in development. Thereafter, the
      percentage of transcripts directed by the distal promoter gradually declined, and
      remained at a low but detectable level (approximately 5% of total MOR
      transcripts) throughout development and adulthood. Conversely, a progressive
      increase of the contribution of the proximal promoter to MOR transcription was
      observed during development, reaching its maximum in the adult. In summary, our
      results demonstrated the pivotal role of the proximal promoter in directing MOR
      transcription during murine development.

PMID- 12225874
TI  - JunB and Bcl-2 overexpression results in protection against cell death of nigral
      neurons following axotomy.
AB  - Transection of the medial forebrain bundle is a well established approach to
      investigate neuronal cell body response in the derived neuronal populations of
      the substantia nigra pars compacta (SNC). This model of central axotomy leads in
      mouse within 50 days post transection to degeneration of up to 70% of the
      affected SNC neurons. A central component of the axotomy induced alterations
      leading to neuronal degeneration is the rapid induction, lasting expression and
      activation of the c-Jun transcription factor. However, the role of c-Jun in the
      process of neuronal degeneration is not fully understood. Since null mutations of
      c-Jun cause embryonic lethality, this study was designed to investigate the
      impact of two c-Jun modulating proteins on neuronal survival after axotomy in
      transgenic mice: JunB, a Jun family member affecting c-Jun expression, and Bcl-2,
      an antiapoptotic protooncogene interacting among others with the c-Jun N-terminal
      kinases. In JunB as well as in Bcl-2 transgenic mice the long term survival rate
      of transected SNC neurons was remarkably increased when compared to wildtype
      controls. These effects were obviously achieved by cellular modulations directly
      following axotomy: Whereas JunB overexpression attenuated c-Jun induction and
      simultaneously led to a higher phosphorylation rate of c-Jun in SNC neurons, Bcl
      2 overexpression did not influence c-Jun expression, but resulted in a reduced
      phosphorylation state of c-Jun in transected SNC neurons. We therefore conclude
      that the early phosphorylation rate of c-Jun might play an important role for the
      long term fate of transected neurons.

PMID- 12225875
TI  - The heterogeneity of central benzodiazepine receptor subtypes in the human
      hippocampal formation, frontal cortex and cerebellum using [3H]flumazenil and
      zolpidem.
AB  - The ability of clonazepam and zolpidem to displace [3H]flumazenil binding was
      measured in the human hippocampal formation, frontal cortex (BA9) and the
      cerebellum using in situ radioligand binding and autoradiography. The use of high
      resolution phosphorimaging in all regions indicated the displacement of
      [3H]flumazenil by clonazepam was monophasic with K(i) values ranging from 2.73+/
      0.17 to 6.49+/-0.21 nM. [3H]flumazenil binding that was not displaced by
      clonazepam ranged from 3.39+/-0.86 to 7.15+/-1.11%. The ability of zolpidem to
      displace [3H]flumazenil was also monophasic in the frontal cortex and cerebellum
      with K(i) values of 37.53+/-1.79 and 31.80+/-1.68 nM, respectively. In contrast,
      within all hippocampal regions, zolpidem displacement of [3H]flumazenil was
      biphasic, with K(i) values for the high affinity site ranging from 0.13+/-0.04 to
      0.54+/-0.03 nM, whereas the low affinity site was between 84.98+/-1.58 and
      98.84+/-1.89 nM. In addition, zolpidem insensitive [3H]flumazenil binding was
      observed to vary markedly between brain regions, ranging between 37.85+/-1.60 and
      6.13+/-0.83%. In conclusion, the present results indicate that in situ
      radioligand binding and high-resolution phosphorimaging techniques can be
      utilized to measure the differential displacement of [3H]flumazenil by zolpidem
      and clonazepam. Moreover, our data suggests that the differential distribution of
      the zolpidem insensitive component of [3H]flumazenil binding is an indicator of
      GABA/BZ receptors assembled by different subunits within the human brain.

PMID- 12225876
TI  - Expression patterns of tau mRNA isoforms correlate with susceptible lesions in
      progressive supranuclear palsy and corticobasal degeneration.
AB  - Deposition of hyperphosphorylated tau (p-tau) has been observed in several
      neurodegenerative diseases. The six isoforms of tau are divided into two main
      groups including three repeat (3R) and four repeat (4R) microtubule-binding
      domains. Using quantitative RT-PCR method and immunohistochemistry with
      phosphorylation dependent anti-tau antibody (AT8), we investigated the expression
      level of tau mRNA isoforms in the frontal cortex and globus pallidus of patients
      with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) to
      determine whether altered expression patterns of tau mRNA isoforms correlate with
      p-tau accumulation. The 4R/3R ratios in frontal cortices of CBD and globus
      pallidus of PSP and CBD were significantly higher than the control (P<0.05).
      There was no correlation between the expression patterns of tau mRNA isoforms and
      p-tau accumulation. Our findings suggest that neurodegeneration of PSP and CBD
      could be regulated by alternative splicing of tau mRNA to yield high 4R/3R ratio.
      In addition, the lack of correlation between the expression pattern of tau mRNA
      isoforms and p-tau accumulation suggests that not only alternative splicing of
      tau mRNA, but also other factors such as post-transcriptional or translational
      modifications may play a role in the pathogenesis of specific neurodegeneration
      in PSP and CBD.

PMID- 12225877
TI  - Sex differences in the regulation of tyrosine hydroxylase gene transcription by
      estrogen in the locus coeruleus of TH9-LacZ transgenic mice.
AB  - Although estrogen is recognized increasingly as having an important role in
      modulating extrahypothalamic brain function, the mechanisms through which this
      occur are not well established. The norepinephrine (NE) neurons of the locus
      coeruleus provide an important neuromodulatory influence upon multiple neural
      networks throughout the brain and estrogen has been implicated in their
      regulation. Using a tyrosine hydroxylase (TH) promoter-LacZ transgenic mouse
      model, which enables rates of TH gene transcription to be examined in vivo, we
      have examined here whether estrogen regulates expression of the TH gene in the
      locus coeruleus of males and females. Optical area measurements of Xgal reaction
      product in the locus coeruleus revealed that gonadectomy exerted opposite effects
      on TH gene transcription in males and females; transgene expression was increased
      in males (P<0.01) but reduced in females (P<0.05). Estrogen reversed these
      effects in both sexes by suppressing gene expression in males (P<0.05) but
      elevating it in the female (P<0.05). These studies reveal a marked and unexpected
      sex difference in the regulation of TH gene activity in the mouse. While estrogen
      in the male, synthesized from circulating testosterone, suppresses TH gene
      transcription, estrogen in the female enhances TH promoter activity. The present
      results indicate that estrogen may exert very different sex-dependent effects
      upon the biosynthesis of NE within the locus coeruleus.

PMID- 12225878
TI  - Genes associated with pro-apoptotic and protective mechanisms are affected
      differently on exposure of neuronal cell cultures to arsenite. No indication for
      endoplasmic reticulum stress despite activation of grp78 and gadd153 expression.
AB  - The effect of arsenite exposure on cell viability, protein synthesis, energy
      metabolism and the expression of genes coding for cytoplasmic (hsp70) and
      endoplasmic reticulum (ER; gadd153, grp78, grp94) stress proteins was
      investigated in primary neuronal cell cultures. Furthermore, signs of ER stress
      were evaluated by investigating xbp1 mRNA processing. Arsenite levels of 30 and
      100 microM induced severe cell injury. Protein synthesis was reduced to below 20%
      of control in cultures exposed to 30 and 100 microM arsenite for 1 h, and it
      remained markedly suppressed until 24 h of exposure. Arsenite induced a transient
      inhibition of energy metabolism after 1 h of exposure, but energy state recovered
      completely after 3 h. Arsenite exposure affected the expression and translation
      of genes coding for HSP70 and GRP78, GRP94, GADD153 to different extents. While
      hsp70 mRNA levels rose drastically, approximally 550-fold after 6 h exposure,
      HSP70 protein levels did not change over the first 6 h. On the other hand,
      gadd153 mRNA levels rose only approximately 14-fold after 6 h exposure, while
      GADD153 protein levels were markedly increased after 3 and 6 h exposure. HSP70
      protein levels were markedly increased and GADD153 protein levels decreased to
      almost control levels in cultures left in arsenite solution for 24 h, i.e. when
      only a small fraction of cells had escaped arsenite toxicity. Arsenite exposure
      of neurons thus induced an imbalance between pro-apoptotic and survival
      activating pathways. Despite the marked increase in gadd153 mRNA levels, we did
      not observe signs of xbp1 processing in arsenite exposed cultures, indicating
      that arsenite did not produce ER stress.

PMID- 12225879
TI  - Effect of Brn-3a deficiency on nociceptors and low-threshold mechanoreceptors in
      the trigeminal ganglion.
AB  - Immunohistochemistry for protein gene product 9.5 (PGP 9.5, a neuron specific
      protein) and vanilloid receptor 1-like receptor (VRL-1, a marker for medium-sized
      to large primary nociceptors) were used to assess the effects of Brn-3a
      deficiency on neuronal innervation of oral tissues and neurons of the trigeminal
      ganglion (TG). In the knockout mouse, the number of PGP 9.5-immunoreactive (-ir)
      nerve fibers decreased in the facial cutaneous and oral mucous epithelia, as well
      as the incisor and molar tooth germs. The reduction of PGP 9.5-ir Merkel endings
      was also observed in some vibrissae. No obvious change was detected in other
      tissues. Cell size analysis demonstrated that the proportion of small neurons
      markedly increased while that of medium-sized and large neurons significantly
      decreased in the TG of the mutant. Moreover, Brn-3a deficiency caused the
      disappearance of TG neurons which were immunoreactive for VRL-1. Together, our
      data suggest that nociceptors and low-threshold mechanoreceptors with medium
      sized to large cell bodies may be sensitive to the loss of Brn-3a.

PMID- 12225880
TI  - Involvement of the calcium-independent receptor for alpha-latrotoxin in brain
      ischemia.
AB  - Cerebral ischemia is caused by a reduced blood supply to neurons, and
      vulnerability to neurodegeneration varies considerably among neuronal types. In
      hippocampus, neurons in the CA1 region are more susceptible to ischemia-induced
      neuronal death than neurons in the CA3 region, and in response to transient
      forebrain ischemia a family of calcium-dependent receptors for alpha-latrotoxin
      is differentially expressed in the two regions. Here, we report that an ischemic
      insult up-regulated a family of calcium-independent receptors for alpha
      latrotoxin (CIRL) mRNAs in CA1 neurons and down-regulated their mRNAs in CA3
      neurons. Furthermore, antisense oligonucleotides complementary to CIRL-1 mRNA or
      CIRL-3 mRNA suppressed neuronal death associated with hypoxia in hippocampal and
      cortical cell cultures. The observed region-specific CIRL mRNA expression in
      hippocampus and an in vitro rescue experiment by antisense oligonucleotides
      against CIRL mRNAs suggest a functional importance of CIRL in neurodegeneration.

PMID- 12225881
TI  - Presence of claudins mRNA in the brain. Selective modulation of expression by
      kindling epilepsy.
AB  - In the central nervous system, the junctional types that establish and maintain
      tissue architecture include gap junctions, for cytoplasmic connectivity, and
      tight junctions, for paracellular and/or cell polarity barriers. Connexins are
      the integral membrane proteins of gap junctions, whereas occludin and members of
      the multigene family of claudins form tight junctions. In the brain, there are no
      transendothelial pathways, as continuous tight junctions are present between the
      endothelial cells. Thus, they provide a continuous cellular barrier between the
      blood and the insterstitial fluid. However, several brain pathologies, including
      epilepsy, are known to alter the permeability of the blood-brain barrier and to
      cause edema. Therefore, since claudins, as constitutive proteins of tight
      junctions are likely candidates for modulation under pathological states, we
      explored their normal pattern of expression in the brain and its modulation by
      seizures. We found that several members of this family are normally expressed in
      the hippocampus and cortex. Interestingly, claudin-7 is expressed in the
      hippocampus but not in the cortex. On the other hand, the expression of claudin-8
      is selectively down-regulated in the hippocampus as kindling evolves. These
      results link for the first time the modulation of expression of a tight junction
      protein to abnormal neuronal synchronization that could probably be reflected in
      permeability changes of the blood-brain barrier or edema.

PMID- 12225882
TI  - Cell-type-specific expression of protein tyrosine kinase-related receptor RYK in
      the central nervous system of the rat.
AB  - The mammalian RYK is an orphan receptor that contains a catalytically inactive
      tyrosine-kinase-related domain. Its Drosophila homolog, Lio/Drl, is required for
      axon pathfinding in developing brain. Our previous study suggested that RYK mRNA
      is expressed in nestin-positive progenitor cells and neurons. In the present
      study, immunohistochemistry has been used to further localize RYK in the central
      nervous system of rats to identify the lineage of the RYK-expressing cells. In
      the embryonic forebrain, RYK colocalized with nestin in the ventricular zone and
      with MAP2 in the cortical plate, suggesting that RYK is expressed in neural
      progenitor cells and neurons. Localization of RYK in embryonic spinal cord also
      suggested its expression in both cell types. In primary cultures of rat cerebrum,
      RYK expression was observed in all neurons, as well as in a significant
      population of oligodendrocytes, O-2A progenitor cells, and type-2 astrocytes.
      However, no RYK expression was detected in type-1 astrocytes or microglia.
      Multipotent neural stem cell line MNS-70 was also analyzed for expression of RYK,
      and most of the cells were positive for both RYK and nestin in the
      undifferentiated stage. In the differentiated stage, expression of RYK was
      detected in the neurons, but not in type-1 astrocytes. In conclusion, RYK is
      expressed in nestin-positive progenitor cells and neurons, and in a certain
      population of oligodendrocytes, O-2A progenitor cells, and type-2 astrocytes in
      developing CNS. These findings show that expression of RYK in rat CNS is tightly
      regulated in a cell-type-specific manner.

PMID- 12225883
TI  - Phagocytotic removal of apoptotic, inflammatory lymphocytes in the central
      nervous system by microglia and its functional implications.
AB  - Apoptotic cell death of inflammatory T cells is an established mechanism to
      terminate an autoimmune inflammatory response in the rodent and human central
      nervous system (CNS). The efficient clearance of apoptotic cells protects the
      tissue from leakage of potentially harmful substances from secondary necrotic
      cells. As the resident phagocyte, the microglial cell is the primary candidate
      for the clearance of apoptotic lymphocytes. Furthermore, the phagocytosis of
      apoptotic cells is accompanied by a spectrum of anti-inflammatory effects. In
      this review, we focus on the mechanisms for removal of apoptotic inflammatory
      cells by microglia in the central nervous system and their functional
      consequences.

PMID- 12225884
TI  - Induction of macrophage-derived chemokine/CCL22 expression in experimental
      autoimmune encephalomyelitis and cultured microglia: implications for disease
      regulation.
AB  - Macrophage-derived chemokine (MDC/CCL22) and its receptor CCR4 have been
      implicated in chronic inflammatory processes and in the homing of monocytes, Th2
      cells and regulatory T-cell subsets. Here, we demonstrate that MDC and CCR4 mRNAs
      are expressed in the central nervous system (CNS) of mice developing relapsing
      remitting and chronic-relapsing forms of experimental autoimmune
      encephalomyelitis (EAE). By immunohistochemistry, we show that MDC is produced by
      CNS-infiltrating leukocytes and intraparenchymal microglia, whereas CCR4 is
      expressed on some invading leukocytes. Upon in vitro activation, mouse microglia
      express MDC transcripts and secrete bioactive MDC that induces chemotaxis of Th2,
      but not Th1 cells. We suggest that MDC produced by microglia could regulate Th1
      mediated CNS inflammation by facilitating the homing of Th2 and, possibly,
      regulatory T cells into the lesion site.

PMID- 12225885
TI  - Borrelia burgdorferi induces inflammatory mediator production by murine
      microglia.
AB  - Lyme disease has been associated with damaging inflammation within the central
      nervous system. In the present study, we demonstrate that Borrelia burgdorferi is
      a significant stimulus for the production of IL-6, TNF-alpha, and PGE(2) by
      microglia. This effect is associated with induction of NF-kappaB, and increased
      expression of Toll-like receptor 2 and CD14, receptors known to underlie
      spirochete activation of other immune cell types. These studies identify
      microglia as a previously unappreciated source of inflammatory mediator
      production following challenge with B. burgdorferi. Such production may play an
      important role during the development of Lyme neuroborreliosis.

PMID- 12225886
TI  - Peripheral macrophage recruitment in cuprizone-induced CNS demyelination despite
      an intact blood-brain barrier.
AB  - The contribution of peripheral macrophage was assessed in cuprizone intoxication,
      a model of demyelination and remyelination in which the blood-brain barrier
      remains intact. Flow cytometry of brain cells isolated from cuprizone-treated
      mice revealed an increase in the percentage of Mac-1(+)/CD45(hi) peripheral
      macrophage. To confirm these results in situ, C57BL/6 mice were lethally
      irradiated, transplanted with bone marrow from GFP-transgenic mice, and exposed
      to cuprizone. GFP(+) peripheral macrophages were seen in the CNS after 2 weeks of
      treatment, and infiltration continued through 6 weeks. While the peripheral
      macrophages were far outnumbered by the resident microglia, their recruitment
      across the blood-brain barrier alludes to a potentially important role.

PMID- 12225887
TI  - Vgamma9Vdelta2 T cells recovered from eyes of patients with Behcet's disease
      recognize non-peptide prenyl pyrophosphate antigens.
AB  - The phenotype and antigen-specificity of T cells expanded by mitogenic
      stimulation from intra-ocular fluid (IOF) samples of affected eyes of six
      Behcet's disease (BD) patients, and seven patients with other uveitis entities,
      were determined. High numbers of gammadelta T cells, predominantly Vgamma9Vdelta2
      T cells, were only detected in the IOF-derived TCL of three BD patients. Whereas
      no TCL responded to heat shock protein (HSP) 65 kDa, reactivity to isopentyl
      pyrophosphate (IPP) and related non-peptide prenyl pyrophosphates (PPP) was
      restricted to the gammadelta T cell containing TCL. Upon IPP stimulation, these
      TCL secreted IFN-gamma but no IL-4. By single-cell analysis of intracellular IFN
      gamma production and CD69 expression the IOF-derived IPP-specific T cells were
      identified as CD4(-)CD8(-) gammadelta T cells. The data presented suggest the
      infiltration of PPP-specific Vgamma9Vdelta2 Th1-like cells into the eye of BD
      patients with uveitis.

PMID- 12225888
TI  - Effects of D2-dopamine and alpha-adrenoceptor antagonists in stress induced
      changes on immune responsiveness of mice.
AB  - The involvement of catecholamine receptors (alpha-adrenergic, D2-dopamine (DA))
      was investigated in restraint stress influenced immune responses with concomitant
      changes of G-protein signal transduction. Impairment of the spleen morphology,
      TH1/TH2 cytokine network and natural killer (NK) cell function was observed. In
      vivo administration of specific antagonists prior to restraint stress reversed
      the immunosuppression. These findings demonstrate that D2-type dopaminergic
      mechanism represents the dominant component in regulation of
      Galphas/Galphai(1,2)/Galphaq/11-protein signal transduction and contribute to
      cell responses at postreceptor level of both, central nervous and immune systems.
      G-protein-coupled receptors (GPCRs) can modulate cytokine production and may play
      a regulatory role in immune effector mechanisms.

PMID- 12225889
TI  - Down-regulation of experimental allergic encephalomyelitis in DA rats by
      tiazofurin.
AB  - The immunomodulatory potential of tiazofurin (TR) on experimental autoimmune
      encephalomyelitis (EAE) was investigated. Given continuously, TR dose-dependently
      suppressed the development of EAE in Dark Agouti (DA) rats immunized with either
      rat spinal cord homogenate (SCH) or myelin oligodendrocyte glycoprotein (MOG).
      Amelioration of clinical signs was also obtained when the drug was administered
      during the inductive phase only (day 0 to 8), or during the effector phase (day
      10 to 20) of the disease. Efficacy of TR was further evaluated by adoptive
      transfer of the disease with myelin basic protein (MBP)-sensitized draining lymph
      node cells (DLNC). Cells from TR-protected rats failed to transfer the disease
      into naive syngeneic recipients; in addition, TR treatment of recipient rats that
      had received MBP-sensitized lymphoid cells diminished the adoptively transferred
      EAE. A reduction of clinical EAE in TR-treated rats was accompanied with the
      absence of mononuclear infiltration in the spinal cord and defective adhesive
      cell-cell interactions. The anti-MOG autoAb production was also decreased.
      Importantly, no evidence for a generalized impairment of the T cell activity, nor
      decreased in vitro proliferative antigen specific response of LNC from TR-treated
      animals was found. These results suggest that TR exerts its EAE protective and
      suppressive effects by limiting adhesive interactions involved in the autoimmune
      pathogenic process, and due to the lack of general immunosuppressive activity, it
      should be considered as a candidate drug for the treatment of neuroinflammatory
      diseases like multiple sclerosis (MS).

PMID- 12225890
TI  - Myelin specific Th1 cells are necessary for post-traumatic protective
      autoimmunity.
AB  - Myelin-specific encephalitogenic T cells, when passively transferred into rats or
      mice, cause an experimental autoimmune disease. Previous studies by our group
      have shown that (a) the same cells also significantly reduce post-traumatic
      degeneration in these animals after injury to the central nervous system, (b)
      this beneficial autoimmunity is a physiological response, and (c) animals differ
      in their ability to resist injurious conditions, and the ability to resist post
      traumatic degeneration correlates with resistance to the development of an
      autoimmune disease. Here we show that optic nerve neurons in both resistant and
      susceptible rat strains can be protected from secondary degeneration after crush
      injury by immunization with myelin basic protein emulsified in complete or
      incomplete Freund's adjuvant. We provide evidence that potentially destructive
      autoimmunity (causing autoimmune disease) and beneficial autoimmunity (causing
      improved neuronal survival) both result from activity of the same myelin
      specific, proinflammatory Th1 cells. We further show that following passive
      transfer of such Th1 cells, the expression of their beneficial potential depends
      on the activity of an additional T cell (CD4(+)) population. By identifying the
      additional cellular component of autoimmune neuroprotection, we may be able to
      take meaningful steps toward achieving neuroprotection without risk of
      accompanying autoimmune disease.

PMID- 12225891
TI  - Characterization of microglial responses to Staphylococcus aureus: effects on
      cytokine, costimulatory molecule, and Toll-like receptor expression.
AB  - Microglia participate in innate immune responses in the central nervous system
      (CNS). This work demonstrates that microglia can recognize heat-inactivated
      Staphylococcus aureus and its cell wall product peptidoglycan (PGN) through the
      elaboration of numerous proinflammatory cytokines and chemokines. Microglia also
      exhibited S. aureus bactericidal activity. Microglia constitutively expressed low
      levels of Toll-like receptor 1 (TLR1), TLR2, TLR6, and CD14, all of which were
      enhanced following S. aureus exposure. Activation of resident microglia by S.
      aureus may serve to amplify the CNS antibacterial immune response through the
      release of cytokines, chemokines, and induction of bactericidal activity.

PMID- 12225892
TI  - Novel orphanin FQ/nociceptin transcripts are expressed in human immune cells.
AB  - The opioid-like receptor (NOP) is widely expressed throughout the human immune
      system. Here, we report that human peripheral blood lymphocytes (PBLs) express
      transcripts encoding the NOP receptor agonist, orphanin FQ/nociceptin (OFQ/N).
      OFQ/N transcripts in resting PBLs were restricted to CD19+B cells and contained a
      novel 5' exon (ImEx2b), replacing exons 1 and 2 found in neuronal transcripts.
      Translation of ImEx2b-containing transcripts resulted in truncated OFQ/N
      precursors lacking a classical signal peptide. Mitogen activation of PBLs
      dramatically up-regulated neuronal-like transcripts, predominantly in CD3+T
      cells. Overall, this suggests different promoters direct specific OFQ/N
      transcript expression in immune cells.

PMID- 12225893
TI  - Nitric oxide synthase I and VIP-activated signaling are affected in salivary
      glands of NOD mice.
AB  - The autoimmune sialadenitis developed by non-obese diabetic (NOD) mice is
      considered a suitable model to study the ethiopathogenic mechanisms leading to
      sicca symptoms in Sjogren's syndrome (SS). Evidence supporting a neural rather
      than immune origin of the secretory dysfunction has been provided. As both nitric
      oxide and vasoactive intestinal peptide (VIP) are common messengers to nervous
      and immune systems mediating secretory and inflammatory responses, we examined
      nitric oxide synthase (NOS) activity with special focus on VIP-mediated effects
      in salivary glands of NOD mice. We found a decreased NOS activity and expression
      in major salivary glands of NOD mice with respect to control mice. In addition,
      there was a deficient VIP-activated signaling associated with a reduced saliva
      and amylase secretion in response to VIP. Our results support the hypothesis of
      an impaired balance of neuroimmune interactions in salivary glands as early
      events to take place in the progressive loss of secretory function of NOD mice.

PMID- 12225894
TI  - Infiltration of T-lymphocytes in the brain after anterior chamber inoculation of
      a neurovirulent and neuroinvasive strain of HSV-1.
AB  - Following anterior chamber (AC) inoculation of BALB/c mice with the KOS strain of
      herpes simplex virus type 1 (HSV-1), or with H129, a neuroinvasive and
      neurovirulent strain of HSV-1, both strains of virus spread from the injected eye
      through the brain to cause retinitis. However, KOS-infected mice develop
      retinitis in the uninoculated eye only, whereas H129-infected mice develop
      bilateral retinitis. Previous studies have shown that infiltrating T-cells in the
      suprachiasmatic nuclei (SCN) of the hypothalamus of KOS-infected mice concomitant
      with or before virus protect KOS-infected mice from ipsilateral retinitis. To
      determine the timing of T cell infiltration and cytokine production in the brain
      of H129-infected mice, adjacent, frozen sections of the brain were immunostained
      for virus, T-cells, IL-2, TNF-alpha or IFN-gamma. T-cells infiltrated the brains
      of H129-infected mice and cytokines were produced in infected tissues. However,
      virus spread to the optic nerve and retina of both the inoculated and
      uninoculated eye before T-cells and cytokines were detected in the SCN of H129
      infected mice. These results suggest that infiltrating T-cells in the SCN of H129
      infected mice may arrive too late to prevent the spread of virus into the optic
      nerves and retinas and thus prevent development of bilateral retinitis in
      infected mice.

PMID- 12225895
TI  - A synthetic androstene derivative and a natural androstene metabolite inhibit
      relapsing-remitting EAE.
AB  - Experimental allergic encephalomyelitis (EAE), a Th1 polarized demyelinating
      disease of the central nervous system (CNS), shares many pathological and
      clinical similarities with multiple sclerosis (MS), and thus represents an
      attractive animal model for this disease. The goal of this study was to evaluate
      the suppressive effects of fluasterone (HE2500), a synthetic androstene
      derivative, and androstenetriol (HE2200), a natural androstene hormone on EAE.
      SJL mice were immunized with proteolipid protein (PLP) 139-151 peptide/CFA to
      induce EAE. Starting on day -7, animals were given daily injections (s.c.) of
      derivatives (3.0 mg) in vehicle, or vehicle alone for 33 days. Both HE2500 and
      HE2200 significantly delayed the onset, reduced the peak clinical score and
      cumulative disease index of EAE, and prevented or significantly attenuated
      relapses. Lower doses or other routes of administration were less effective.
      Moreover, T cells from treated mice had significantly reduced PLP 139-151
      specific T cell proliferation responses and reduced numbers of TNF-alpha- and IFN
      gamma-producing cells in the CNS. Daily treatment of B10.PL mice with HE2500,
      starting on day 0, completely prevented the development of disease in these
      animals. Finally, SJL mice treated with HE2500 at EAE onset showed significantly
      reduced mean clinical scores. Thus, these compounds, which have been reported to
      have a few androgenic or estrogenic side effects, appear to have a potent
      inhibitory activity in EAE. These observations suggest that HE2500 and/or HE2200
      limit the production of autoimmune Th1 associated cytokines, and ultimately may
      be beneficial for patients with MS or other autoimmune diseases.

PMID- 12225896
TI  - Differential expression of nicotinic acetylcholine receptor subunits in fetal and
      neonatal mouse thymus.
AB  - Studies were initiated to identify nicotinic acetylcholine receptor (nAChR)
      subunits and subtypes expressed in the developing immune system and cell types on
      which nAChR are expressed. Reported here are reverse transcription-polymerase
      chain reactions (RT-PCR) studies of nAChR alpha2-alpha7 and beta2-beta4 subunit
      gene expression using fetal or neonatal regular or scid/scid C57BL/6 mouse
      thymus. Findings are augmented with studies of murine fetal thymic organ cultures
      (FOTC) and of human peripheral lymphocytes. Novel partial cDNA sequences were
      derived for mouse nAChR alpha2, alpha3, beta3 and beta4 subunits, polymorphisms
      were identified in mouse nAChR alpha4, alpha7 and beta2 subunits, and recently
      derived sequences for mouse nAChR alpha5 and alpha6 subunits were confirmed.
      Thymic stromal cells appear to express nAChR alpha2, alpha3, alpha4, alpha7 and
      beta4 subunits, perhaps in addition to alpha5 and beta2 subunits, in a pattern
      reminiscent of expression in the developing brain. Immature T cells appear to
      express alpha3, alpha5, alpha7, beta2 and beta4 subunits, just as do neural crest
      derived cells targeted by cholinergic innervation. Peripheral T cells seem to
      express an unusual profile of alpha2, alpha5 and alpha7 subunits, perhaps
      indicating that their nAChR express yet-to-be-identified assembly partners or
      that T cell nicotinic responsiveness occurs through homomeric nAChR composed of
      alpha7 subunits. Our findings are consistent with published work but show a much
      wider array of nAChR subunit gene expression in mouse thymic stromal and/or
      lymphoid cells and evidence for developmental regulation of nAChR subunit
      expression. These studies suggest important roles for nAChR in immune system
      development and function and in the neuroimmune network.

PMID- 12225897
TI  - Production and secretion of calcitonin gene-related peptide from human
      lymphocytes.
AB  - Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide, which is
      mainly present in primary sensory nerves. Although our previous study has shown
      that rat lymphocytes can synthesize beta-CGRP, there is no evidence demonstrating
      whether CGRP can be synthesized by human lymphocytes. In this study, the
      production of CGRP from human lymphocytes from spleen and blood were investigated
      by using CGRP-specific radioimmunoassay (RIA), and RNase protection assay (RPA).
      The results showed that human T lymphocyte mitogen, such as phytohemagglutinin
      (PHA), could time- and dose-dependently induce hCGRP secretion; rhIL-2 alone did
      not effect hCGRP secretion, but it could potentiate PHA-evoked hCGRP secretion
      from human spleen lymphocytes. RPA showed that alpha- and beta-CGRP mRNA were
      both constitutively expressed in unstimulated human peripheral blood mononuclear
      cells (PBMC). PHA could cause beta-hCGRP but not alpha-hCGRP mRNA increase in a
      time-dependent manner. In addition, hCGRP(8-37), a CGRP(1) receptor antagonist,
      enhanced PHA or human interleukin-2 (rhIL-2), induced the proliferation of
      splenocytes and PBMC. These results suggest that hCGRP is produced and secreted
      by human lymphocyte. Lymphocyte mitogen can induce the elevation of beta-CGRP
      synthesis and secretion. The lymphocyte-derived beta-CGRP may inhibit, at least
      in part, lymphocytes proliferation, which are then involved in the modulation of
      human T lymphocyte function in response to immune stimulation.

PMID- 12225898
TI  - The new orally active immunoregulator laquinimod (ABR-215062) effectively
      inhibits development and relapses of experimental autoimmune encephalomyelitis.
AB  - A new orally active drug, laquinimod (ABR-215062), was shown to completely
      inhibit the development of murine acute experimental autoimmune encephalomyelitis
      (EAE). Furthermore, leukocyte infiltration into the central nervous system (CNS)
      was abolished in the laquinimod-treated animals. By direct comparison based on
      dose and total exposure, laquinimod was approximately 20 times more potent than
      the immunomodulator roquinimex. Laquinimod also had clear therapeutic effect when
      given after clinical onset in a chronic relapsing EAE model. It therefore
      represents a new orally active immunoregulatory drug without general
      immunosuppressive properties for the treatment of the autoimmune disease multiple
      sclerosis.

PMID- 12225899
TI  - Interferon-gamma production to inner ear antigens by T cells from patients with
      autoimmune sensorineural hearing loss.
AB  - Autoimmune sensorineural hearing loss (ASNHL) typically produces bilateral
      rapidly progressive loss of hearing over a few days or weeks, but may also
      produce sudden loss over a few hours. The diagnosis is made by excluding
      ototoxicity, systemic disease, and other factors that mimic ASNHL and by showing
      a therapeutic response to corticosteroid treatment. Antibody production and T
      cell proliferative responses to inner ear antigens have been implicated in the
      etiopathogenesis of ASNHL. In the current study, we have extended these
      autoimmune investigations by determining the frequencies of inner ear specific
      IFN-gamma producing T cells in peripheral blood mononuclear cells (PBMC) from
      ASNHL patients and from age- and sex-matched control subjects. ELISPOT analysis
      showed that 25% of ASNHL patients have significant increased frequencies of inner
      ear specific IFN-gamma producing T cells in their PBMC. All control subjects were
      relatively unresponsive. Our results implicate inner ear specific IFN-gamma
      producing proinflammatory T cells in the pathogenesis of ASNHL.

PMID- 12225900
TI  - Cross-reactive anti-galactocerebroside antibodies and Mycoplasma pneumoniae
      infections in Guillain-Barre syndrome.
AB  - Anti-galactocerebroside (GalC) antibodies are reported to be present in GBS
      patients with preceding Mycoplasma pneumoniae (MP) infection. We investigated the
      presence of anti-GalC reactivity in serum of a large group of GBS patients using
      ELISA and compared this with healthy controls and individuals with an
      uncomplicated MP infection. Anti-GalC antibody reactivity was present in 12% of
      the GBS patients. Furthermore, anti-GalC antibodies were associated with MP
      infections, a relatively mild form of the disease and demyelinating features.
      Anti-GalC antibodies cross-reacted with MP antigen. In conclusion, anti-GalC
      antibodies in GBS patients may be induced by molecular mimicry with MP.

PMID- 12225901
TI  - Stiff-man syndrome: identification of 17 beta-hydroxysteroid dehydrogenase type 4
      as a novel 80-kDa antineuronal antigen.
AB  - Stiff-man syndrome (SMS) is a rare autoimmune disorder of the central nervous
      system associated with autoantibodies to glutamate decarboxylase (GAD). We
      isolated five brain-reactive human monoclonal antibodies, with reactivity
      distinct from GAD, from peripheral blood of a patient newly diagnosed with SMS.
      Two antibodies reacted with both Purkinje cells and ependymal cells, and
      precipitated an 80-kDa protein from rat neuronal primary cultures, which was also
      recognized by 12% (3/25) of SMS sera and 13% (2/15) of SMS cerebrospinal fluid
      (CSF) samples. The corresponding antigen was identified as 17 beta-hydroxysteroid
      dehydrogenase type 4 and may represent a possible novel target of autoimmunity in
      SMS.

PMID- 12225902
TI  - The HLA locus and multiple sclerosis in Spain. Role in disease susceptibility,
      clinical course and response to interferon-beta.
AB  - The HLA-DR2 haplotype (DRB1*1501, DQB1*0602) on chromosome 6p21 has consistently
      demonstrated both association and linkage with multiple sclerosis (MS) in case
      control and family studies, particularly in Caucasians of Northern European
      descent. However, the role of a gene within this region in determining clinical
      features or response to immunotherapy remains largely unknown. A new familial MS
      data set from the Mediterranean Spanish Basin was collected according to rigorous
      ascertainment criteria. We confirm, primarily in the cohort originating from
      Continental Spain, that similar to other high-risk groups, there was a
      significant association with HLA-DR2. No other DR or DQ alleles were found to be
      associated with disease susceptibility nor were alleles at the class I A and B
      loci. Overall, the effect of HLA appears to be less substantial than that
      observed in a reference US population with a higher disease incidence. No effect
      of the HLA-DR2 haplotype on age of onset, initial clinical symptoms and disease
      course was observed. Similarly, no difference in the distribution of responders
      and nonresponders to interferon-beta (IFNB) therapy, as defined by primary and
      secondary end points, was observed when individuals were stratified according to
      HLA-DR2 status.

PMID- 12225903
TI  - The expression of apoptosis-regulatory proteins in B lymphocytes from patients
      with multiple sclerosis.
AB  - The pathogenesis of multiple sclerosis (MS) is thought to involve T- and B
      lymphocyte-mediated autoimmunity. However, the mechanisms that regulate
      lymphocyte activity in MS are poorly understood. In normal circumstances,
      programmed cell death (apoptosis) contributes to the maintenance of lymphocytes
      homeostasis and the deletion of autoreactive cells. Cellular commitment to
      apoptosis is partly regulated by the cell death receptor Fas, and the anti
      apoptosis proteins Bcl-2 and FLIP. Although there is emerging evidence that
      dysregulations of apoptotic pathways play a role in T-cell autoimmunity in MS,
      the expression of apoptosis-regulatory proteins in B cells from MS patients is
      largely unknown. In this study, we analyzed the expression profiles of Fas, Bcl
      2, and FLIP proteins in peripheral B lymphocytes from patients with relapsing
      remitting and progressive MS, and from appropriate controls. We observed a
      significant up-regulation of Bcl-2 and FLIP proteins in B cells from relapsing
      remitting MS when compared to corresponding expression in progressive MS, or in
      noninflammatory neurologic controls and healthy individuals. This cellular
      overexpression of Bcl-2 and FLIP proteins was not affected by treatment with
      interferon-beta, but was also observed in B cells from patients with systemic
      inflammatory diseases. Our findings suggest that cellular overexpression of the
      apoptosis-inhibitory proteins in patients with relapsing MS may promote apoptotic
      resistance of potentially pathogenic, autoreactive B lymphocytes and
      consequently, may allow for continuing autoimmune tissue destruction.

PMID- 12225904
TI  - Sex differences in cytokine responses to myelin peptides in multiple sclerosis.
AB  - Many autoimmune diseases preferentially affect women; however, the underlying
      mechanisms for the sex differences are poorly understood. We examined sex
      dependent differences in the immunologic response to myelin proteins in 22
      multiple sclerosis (MS) patients and 22 healthy controls. Using ELISA spot assay
      (ELISPOT) methodology, interferon (IFN) gamma and IL-5 secretions were examined
      at the single cell level in response to overlapping proteolipid protein (PLP)
      peptides. As previously reported, we observed an overall disease effect in the
      IFNgamma response, such that MS patients were significantly higher than controls.
      With respect to PLP-induced IFNgamma secretion, both MS and control females
      responded higher than their corresponding males. Female MS patients demonstrated
      the highest responses compared to MS males or healthy controls of either sex.
      Although MS females had high IFNgamma responses to PLP, they had no IL-5
      responses at all, suggesting strong Th1 skewing. In contrast, MS males had more
      IL-5 than control males, who lacked IL-5 responses. These IL-5 responses
      suggested that disease and gender are not independent, but rather interact to
      influence the cytokine response to myelin. The data suggest a gender bias towards
      Th1 responses in MS, which may contribute to the female predominance in this
      disease.

PMID- 12225905
TI  - Abnormal expression of CTLA-4 by T cells from patients with myasthenia gravis:
      effect of an AT-rich gene sequence.
AB  - Cytolytic T lymphocyte-associated antigen-4 (CTLA-4) plays a critical role in the
      down-regulation of antigen-activated immune responses. The aberrant CTLA-4
      expression is characterized by low surface and intracellular levels of CTLA-4
      protein, impaired up-regulation of CTLA-4 in T cells in response to ConA
      stimulation and high levels of soluble CTLA-4 (sCTLA-4) in serum. The serum
      levels of sCTLA-4 are positively correlated with the serum concentration of
      antibodies against the acetylcholine receptor. The (AT)(n) polymorphism in the 3'
      untranslated region contributes to decreased mRNA stability and, hence, to
      reduced expression of CTLA-4.

PMID- 12225906
TI  - T cell response to 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in
      multiple sclerosis patients.
AB  - T cell responses targeting myelin antigens are possibly involved in the
      pathogenesis of demyelinating diseases, such as multiple sclerosis (MS). Little
      is known about human T cell responses to 2',3'-cyclic nucleotide 3'
      phosphodiesterase (CNPase), the third most abundant myelin protein. We examined
      the primary peripheral T cell response to CNPase and characterized CNPase
      specific CD4+ long-term T cell lines (TCL) from MS patients and healthy donors.
      The strongest primary responses were found in two MS patients with very active
      disease and were directed against CNP(343-373). We identified immunodominant
      epitope clusters in the regions CNP(343-373) and (356-388) that were recognized
      in the context of MS-associated HLA-DR2 and DR4 molecules. These data provide the
      immunological basis for further investigation of CNPase as a potential target
      self-antigen in MS.

PMID- 12225907
TI  - Maternal antibody-mediated dyslexia? Evidence for a pathogenic serum factor in a
      mother of two dyslexic children shown by transfer to mice using behavioural
      studies and magnetic resonance spectroscopy.
AB  - The causes of dyslexia are unknown, but previous studies have suggested an
      immunological basis in some cases. We hypothesised that maternal antibodies,
      which cross the placenta and bind to fetal antigens, could be responsible,
      particularly when the dyslexia recurs in consecutive pregnancies. We injected
      serum samples from five mothers of two or more children with dyslexia into
      pregnant mice, and tested the offspring for behavioural abnormalities and
      cerebellar metabolites by magnetic resonance spectroscopy (MRS). Mice exposed in
      utero to serum factors from one woman with two dyslexic children, who had also
      had three spontaneous fetal losses, showed deficits in motor tests which
      correlated with cerebellar choline (Cho) and creatine (Cr) levels. These
      preliminary results are consistent with a role for maternal serum factors,
      probably antibodies, in causing some of the features of dyslexia, and possibly in
      other neurodevelopmental disorders.

PMID- 12225909
TI  - Genetic Transformation in Insects. Proceedings of a meeting. Taos, New Mexico,
      USA. February 2001.

PMID- 12225910
TI  - Culicine genomics.

PMID- 12225911
TI  - High-throughput approaches to study salivary proteins and genes from vectors of
      disease.
AB  - Blood-feeding arthropods have in their saliva a variety of molecules that affect
      the vertebrate host's hemostatic, inflammatory, and immune systems. The saliva of
      blood feeders also helps to facilitate infection of the pathogens they carry to
      the host, making vector saliva an attractive target to control pathogen
      transmission. The isolation and identification of salivary molecules from vectors
      of disease has been slow and difficult. Emerging technologies and new approaches
      in the fields of molecular biology and protein chemistry are facilitating this
      work. Massive sequencing of high quality, full-length cDNA libraries, coupled
      with proteomics and functional genomic approaches has led to the discovery of
      novel proteins, transcription products (genes), and biologic activities from the
      salivary glands of blood-feeding arthropods. This review focuses on the biologic
      activities identified in the saliva of various vectors of disease using classic
      biochemical and molecular biology approaches and new types of molecules and
      activities identified with high-throughput strategies.

PMID- 12225912
TI  - Use of the piggyBac transposon for germ-line transformation of insects.
AB  - Germ-line transformation of insects is now possible with four independent
      transposable element vector systems. Among these, the TTAA-insertion site
      specific transposon, piggyBac, discovered in Trichoplusia ni, is one of the most
      widely used. Transformations have been achieved in a wide variety of dipterans,
      lepidopterans, and a coleopteran, and for many species, piggyBac transposition
      was first tested by plasmid-based mobility assays in cell lines and embryos. All
      plasmid and genomic insertions are consistent with the duplication of a TTAA
      insertion site, and most germ-line integrations appear to be stable, though this
      is largely based on stable marker phenotypes. Of the vector systems presently in
      use for non-drosophilids, piggyBac is the only one not currently associated with
      a superfamily of transposable elements, though other elements exist that share
      its TTAA insertion site specificity. While functional piggyBac elements have only
      been isolated from T. ni, nearly identical elements have been discovered in a
      dipteran species, Bactrocera dorsalis, and closely related elements exist in
      another moth species, Spodoptera frugiperda. It appears that piggyBac has
      recently traversed insect orders by horizontal transmission, possibly mediated by
      a baculovirus or other viral system. This interspecies movement has important
      implications for the practical use of piggyBac to create transgenic insect
      strains for field release.

PMID- 12225913
TI  - Fluorescent transformation markers for insect transgenesis.
AB  - The first effectively achieved germ-line transformations of non-drosophilid
      insects were based on mutant rescue of eye color phenotypes. However, for most
      insect species neither visible mutants nor corresponding cloned genes are
      available. Therefore, the development of broadly applicable and reliable
      transformation markers will be of great importance to fully exploit the enormous
      potential transgenic insect technology has to offer. Here we review transposon
      mediated germ-line transformation approaches that employ green fluorescent
      protein (GFP) variants to identify successful gene transfer. Furthermore, we
      provide novel data on the use of DsRed as an additional red fluorescent
      transformation marker for insect transgenesis. In conclusion, fluorescent
      proteins controlled by suitable strong promoters possess ideal characteristics to
      serve as transformation markers for a wide range of insect species.

PMID- 12225914
TI  - Genetic engineering in insects of agricultural importance.
AB  - The past five years have witnessed the extension of genetic transformation
      techniques into 11 insect species covering four orders within the Insecta. While
      the robustness of these transformation systems can be improved, there is now a
      highly likely probability that transformation of a given insect species will
      ensue, provided transposable element-containing plasmid DNA can be effectively
      delivered to the embryo or some other life stage. These developments have shifted
      emphasis to concerns of transgene stability and the regulation of the rearing and
      release of these transgenic insects. They have also led to some elegant
      demonstrations of genetic sexing mechanisms in Drosophila melanogaster with the
      expectation that similar systems be extended into pest insect species. These
      developments and issues are discussed in this short review.

PMID- 12225915
TI  - Re-engineering the sterile insect technique.
AB  - The mass release of sterile insects (the Sterile Insect Technique, SIT) is a
      highly effective area-wide method of pest control with a low environmental
      impact. SIT relies on the sterilization by irradiation of large numbers of
      insects. This has unavoidable costs in terms of the fitness of the irradiated
      insects and the financial requirements of constructing and operating the
      radiation facility. In many cases it is considered important to release only
      males, but large-scale sex-separation is also problematic. I have proposed that
      both of these difficulties can be overcome by using engineered strains of insects
      carrying a dominant, repressible, lethal gene or genetic system. As a proof of
      principle, my group and others have constructed strains of Drosophila
      melanogaster with the required genetic properties.

PMID- 12225917
TI  - Design and function of transcriptional switches in Drosophila.
AB  - Extensive genetic and biochemical analysis of Drosophila melanogaster has made
      this system an important model for characterization of transcriptional regulatory
      elements and factors. Given the striking conservation of transcriptional controls
      in metazoans, general principles derived from studies of Drosophila are expected
      to continue to illuminate transcriptional regulation in other systems, including
      vertebrates. With improvement in technologies for genetic manipulation of
      insects, research in Drosophila will also aid the design of systems for
      controlled expression of genes in other hosts. This review focuses on recent
      advances from Drosophila in analysis of the functional components of
      transcriptional switches, including basal promoters, enhancers, boundary
      elements, and maintenance elements.

PMID- 12225916
TI  - Drosophila germline invasion by the endogenous retrovirus gypsy: involvement of
      the viral env gene.
AB  - The endogenous retrovirus gypsy is expressed at high levels in mutant flamenco
      female flies. Gypsy viral particles extracted from such flies can infect naive
      flamenco individuals raised in the presence of these extracts mixed into their
      food. This results in the integration of new proviruses into the germline genome.
      These proviruses can then increase their copy number by (1) expression in the
      flamenco female somatic cells, (2) transfer into the oocyte and (3) integration
      into the genome of the progeny. Surprisingly, unlike the infection observed in
      the feeding experiments, this strategy of endogenous proviral multiplication does
      not seem to involve the expression of the viral env gene.

PMID- 12225918
TI  - Molecular biology of mosquito vitellogenesis: from basic studies to genetic
      engineering of antipathogen immunity.
AB  - Elucidation of molecular mechanisms underlying stage- and tissue-specific
      expression of genes activated by a blood meal is of great importance for current
      efforts directed towards utilizing molecular genetics to develop novel strategies
      of mosquito and pathogen control. Regulatory regions of such genes can be used to
      express anti-pathogen effector molecules in engineered vectors in a precise
      temporal and spatial manner, designed to maximally affect a pathogen. The fat
      body is a particularly important target for engineering anti-pathogen properties
      because in insects, it is a potent secretory tissue releasing its products to the
      hemolymph, an environment or a crossroad for most pathogens. Recently, we have
      provided proof of this concept by engineering stable transformant lines of Aedes
      aegypti mosquito, in which the regulatory region A. aegypti vitellogenin (Vg)
      gene activates high-level fat body-specific expression of a potent anti-bacterial
      factor, defensin, in response to a blood meal. Further study of the Vg gene
      utilizing Drosophila and Aedes transformation identified cis-regulatory sites
      responsible for state- and fat body-specific activation of this gene via a blood
      meal-triggered cascade. These analyses revealed three regulatory regions in the
      2.1-kb upstream portion of the Vg gene. The proximal region, containing binding
      sites to EcR/USP, GATA, C/EBP and HNF3/fkh, is required for the correct tissue-
      and stage-specific expression at a low level. The median region, carrying sites
      for early ecdysone response factors E74 and E75, is responsible for a stage
      specific hormonal enhancement of the Vg expression. Finally, the distal GATA-rich
      region is necessary for extremely high expression levels characteristic to the Vg
      gene. Furthermore, our study showed that several transcription factors involved
      in controlling the Vg gene expression, are themselves targets of the blood meal
      mediated regulatory cascade, thus greatly amplifying the effect of this cascade
      on the Vg gene. This research serves as the foundation for the future design of
      mosquito-specific expression cassettes with predicted stage- and tissue
      specificity at the desired levels of transgene expression.

PMID- 12225919
TI  - Pattern recognition proteins in Manduca sexta plasma.
AB  - Recognition of nonself is the first step in mounting immune responses. In the
      innate immune systems of both vertebrates and arthropods, such recognition,
      termed pattern recognition, is mediated by a group of proteins, known as pattern
      recognition proteins or receptors. Different pattern recognition proteins
      recognize and bind to molecules (molecular patterns) present on the surface of
      microorganisms but absent from animals. These molecular patterns include
      microbial cell wall components such as bacterial lipopolysaccharide, lipoteichoic
      acid and peptidoglycan, and fungal beta-1,3-glucans. Binding of pattern
      recognition proteins to these molecular patterns triggers responses such as
      phagocytosis, nodule formation, encapsulation, activation of proteinase cascades,
      and synthesis of antimicrobial peptides. In this article, we describe four
      classes of pattern recognition proteins, hemolin, peptidoglycan recognition
      protein, beta-1,3-glucan recognition proteins, and immulectins (C-type lectins)
      involved in immune responses of the tobacco hornworm, Manduca sexta.

PMID- 12225920
TI  - Insect hemocytes and their role in immunity.
AB  - The innate immune system of insects is divided into humoral and cellular defense
      responses. Humoral defenses include antimicrobial peptides, the cascades that
      regulate coagulation and melanization of hemolymph, and the production of
      reactive intermediates of oxygen and nitrogen. Cellular defenses refer to
      hemocyte-mediated responses like phagocytosis and encapsulation. In this review,
      we discuss the cellular immune responses of insects with emphasis on studies in
      Lepidoptera and Diptera. Insect hemocytes originate from mesodermally derived
      stem cells that differentiate into specific lineages identified by morphology,
      function, and molecular markers. In Lepidoptera, most cellular defense responses
      involve granular cells and plasmatocytes, whereas in Drosophila they involve
      primarily plasmatocytes and lamellocytes. Insect hemocytes recognize a variety of
      foreign targets as well as alterations to self. Both humoral and cell surface
      receptors are involved in these recognition events. Once a target is recognized
      as foreign, hemocyte-mediated defense responses are regulated by signaling
      factors and effector molecules that control cell adhesion and cytotoxicity.
      Several lines of evidence indicate that humoral and cellular defense responses
      are well-coordinated with one another. Cross-talk between the immune and nervous
      system may also play a role in regulating inflammation-like responses in insects
      during infection.

PMID- 12225921
TI  - Implications of Time Bomb model of ookinete invasion of midgut cells.
AB  - In this review, we describe the experimental observations that led us to propose
      the Time Bomb model of ookinete midgut invasion and discuss potential
      implications of this model when considering malaria transmission-blocking
      strategies aimed at arresting parasite development within midgut cells. A
      detailed analysis of the molecular interactions between Anopheles stephensi
      midgut epithelial cells and Plasmodium berghei parasites, as they migrate through
      midgut cells, revealed that ookinetes induce nitric oxide synthase (NOS)
      expression, remodeling of the actin cytoskeleton and characteristic morphological
      changes in the invaded epithelial cells. Parasites inflict extensive damage that
      ultimately leads to genome fragmentation and cell death. During their migration
      through the cytoplasm, ookinetes release a subtilisin-like protease (PbSub2) and
      the surface protein (Pbs21). The model proposes that ookinetes must escape
      rapidly from the invaded cells, as the responses mediating cell death could be
      potentially lethal to the parasites. In other words, the physical and/or chemical
      damage triggered by the parasite can be thought of as a 'lethal bomb'. Once this
      cascade of events is initiated, the parasite must leave the cellular compartment
      within a limited time to escape unharmed from the 'bomb' it has activated. The
      midgut epithelium has the ability to heal rapidly by 'budding off' the damaged
      cells to the midgut lumen without losing its integrity.

PMID- 12225922
TI  - Engineering mosquito resistance to malaria parasites: the avian malaria model.
AB  - Genetic approaches to controlling the transmission of mosquito-borne diseases are
      being developed to augment the available chemical control practices and
      environmental manipulation methods. Much progress has been made in laboratory
      based research that seeks to develop antipathogen or antivector effector genes
      and methods for genetically manipulating host vector strains. Research is
      summarized here in the development of a malaria-resistant phenotype using as a
      model system the avian parasite, Plasmodium gallinaceum, and the mosquito, Aedes
      aegypti. Robust transformation technology based on a number of transposable
      elements, the identification of promoter regions derived from endogenous mosquito
      genes, and the development of single-chain antibodies as effector genes have made
      it possible to produce malaria-resistant mosquitoes. Future challenges include
      discovery of methods for spreading antiparasite genes through mosquito
      populations, determining the threshold levels below which parasite intensities of
      infection must be held, and defining the circumstances in which a genetic control
      strategy would be employed in the field.

PMID- 12225923
TI  - Plasmodium-mosquito interactions, phage display libraries and transgenic
      mosquitoes impaired for malaria transmission.
AB  - Malaria continues to kill millions of people every year and new strategies to
      combat this disease are urgently needed. Recent advances in the study of the
      mosquito vector and its interactions with the malaria parasite suggest that it
      may be possible to genetically manipulate the mosquito in order to reduce its
      vectorial capacity. Here we review the advances made to date in four areas: (1)
      the introduction of foreign genes into the mosquito germ line; (2) the
      characterization of tissue-specific promoters; (3) the identification of gene
      products that block development of the parasite in the mosquito; and (4) the
      generation of transgenic mosquitoes impaired for malaria transmission. While
      initial results show great promise, the problem of how to spread the blocking
      genes through wild mosquito populations remains to be solved.

PMID- 12225924
TI  - Developing arbovirus resistance in mosquitoes.
AB  - Diseases caused by arthropod-borne viruses are increasingly significant public
      health problems, and novel methods are needed to control pathogen transmission.
      The hypothesis underlying the research described here is that genetic
      manipulation of Aedes aegypti mosquitoes can profoundly and permanently reduce
      their competence to transmit dengue viruses to human hosts. Recent key findings
      now allow us to test the genetic control hypothesis. We have identified viral
      genome-derived RNA segments that can be expressed in mosquito midguts and
      salivary glands to ablate homologous virus replication and transmission. We have
      demonstrated that both transient and heritable expression of virus-derived
      effector RNAs in cultured mosquito cells can silence virus replication, and have
      characterized the mechanism of RNA-mediated resistance. We are now developing
      virus-resistant mosquito lines by transformation with transposable elements that
      express effector RNAs from mosquito-active promoters.

PMID- 12225925
TI  - Can insecticide resistance status affect parasite transmission in mosquitoes?

PMID- 12225926
TI  - Introduction to occupational medical ethics.
AB  - Most bioethical advice has focused on the individual physician-patient
      relationship. But the ethical dilemmas confronting occupational medicine are more
      complex, because of the influence of institutional and organizational structure.
      For example, consider conflicts of interest in managed care: Concerns about costs
      to employers are not just economic, to be outweighed by commitments to employee
      health, but also legitimate ethical concerns about fair allocation of resources
      among all employees. Furthermore, in occupational health research, rather than
      thinking of employees as a "vulnerable population" it may be more useful to
      regard them as a distinct community and apply the 23 specified protections of
      communities.

PMID- 12225927
TI  - Codes of ethics (conduct).
AB  - Some international organizations and many societies of health and safety
      professionals have codes of ethics (conduct). The intent is to promote ethical
      behavior, though compliance is voluntary and enforcement is generally not
      possible. It is important that all occupational health and safety professionals
      adopt and live up to the same code. It also is important that the same code of
      conduct apply to industrializing countries just as it applies to developed
      countries. A new International Code of Conduct (Ethics) for Occupational Health
      and Safety Professionals, developed by 40 international health and safety
      professionals and set forth in this article, addresses professional obligations
      and responsibilities and introduces a higher standard of ethical conduct than
      formerly existed.

PMID- 12225928
TI  - Ethical concerns in international occupational health and safety.
AB  - The number of preventable occupational health and safety (OHS) tragedies that
      occur yearly requires a deeper examination of the ethics that inform health and
      safety policies and practices. This article selects a few industrial sectors for
      closer examination to illustrate challenges and opportunities. Topics addressed
      include: equitable distribution of resources, ethically acceptable global
      standards for OHS for all workers, and international use of pesticides and the
      export of banned chemicals. The authors focus on the relationship between less
      developed and developed countries and attempt to identify areas of collaboration
      and potentially positive channels for addressing shortcomings. The agricultural
      sector is examined in particular because of the major role this sector plays in
      developing countries. Finally, the authors examine the impact of globalization on
      the international ethical practice of OHS, especially in relation to vulnerable
      and marginalized groups such as women, children, and informal sector workers, and
      conclude with recommendations for working towards more equitable global ethical
      standards in international OHS.

PMID- 12225930
TI  - Patient advocacy versus employer protection.
AB  - In a departure from the usual Occupational Medicine: State of the Art Reviews
      article, this piece comprises responses from two occupational physicians to the
      question of how balance is achieved between employer and patient interests in
      occupational medicine. The authors discuss the ethical dilemmas that may arise in
      such relationships, negotiation of confrontations, physician responsibilities,
      and conflict resolution.

PMID- 12225929
TI  - Providing employer-arranged occupational medical care: conflicting interests.
AB  - It is said that ethics comprise principles of good conduct or standards governing
      the conduct of the members of a profession. These standards are unbending and
      strict, yet the reality is that occupational health professionals are subject to
      many conflicting pressures. Most of these stresses arise from the fact that
      employers and insurance companies, not worker-patients, fund OH services, and
      these two entities have overlapping, yet distinct, interests. OH professionals
      must consider the health and safety of individual workers as their top priority,
      while also addressing myriad other concerns. This is the moral challenge
      confronting practitioners.

PMID- 12225931
TI  - Confidentiality in occupational medicine.
AB  - Confidentiality of personal medical information is a serious concern in
      occupational medicine. New regulations issued under the Health Insurance
      Portability and Accountablility Act (HIPAA) significantly alter procedures for
      protecting and managing confidential medical information. There are still
      questions about how much the new regulations will affect occupational medicine
      practices, but there will be significant changes in the collection, storage, and
      dissemination of personal medical information in the near future. The
      implications of increased confidentiality concerns on research are also
      considered.

PMID- 12225932
TI  - Legal issues confronting the occupational physician.
AB  - Occupational physicians are frequently participants in a legal arena in which the
      interests of the patient are in conflict with those of the patient's employer.
      What is best for the patient may be viewed as financially burdensome or damaging
      to the employer. Pressures may be brought to bear upon the doctor, who is also
      concerned with furthering business relationships with the employer, to take
      action that is inimical to the patient's well-being. This article addresses legal
      liability and ethical responsibility in three situations: (1) when limitations or
      constraints are placed upon the physician's professional judgment in treating the
      patient; (2) when demands are made upon the physician to release medical
      information regarding a patient; and (3) when the physician is asked to perform a
      medical evaluation for purposes of litigation.

PMID- 12225933
TI  - Ethical issues in occupational health research.
AB  - This is an overview of ethical issues in occupational health research involving
      human subjects. Research that requires human subjects review must be
      distinguished from surveillance or public health practice. Confidentiality and
      privacy concerns are particularly important in an occupational setting because
      individual participants may be identifiable through job title or other
      characteristics, and because there may be concerns about employment
      discrimination associated with participation status or results. Additional issues
      include notification of individual test results to the study participants,
      including whether the results have clinical significance and/or provide other
      potentially relevant information to the study subjects; consent for banking of
      biological specimens for future research (e.g., uses of the specimens, plans for
      anonymization, notification of future results); and the higher level of
      sensitivity of workplace studies involving genetic modifiers of risk. Many
      occupational studies involve no more than minimal risk. Studies that involve
      greater than minimal risk require the investigator to document the potential
      risks and attempt to minimize them.

PMID- 12225934
TI  - Ethical issues in occupational disease outbreak investigations.
AB  - Occupational disease outbreak investigations usually involve rapid, small-scale
      analysis of reports of diseases with a suspected occupational etiology, usually
      in a single workplace or among workers of a single employer. Ethical issues are
      similar to those encountered in epidemiologic studies in the workplace, with the
      added constraints of the need to respond rapidly, limited numbers of subjects,
      low statistical power, and the mandate to issue results even when the ability to
      generalize them is limited. Informed consent, voluntary participation, fairness,
      and confidentiality are major ethical issues in workplace outbreak
      investigations. The obligation to publicly report a workplace hazard when a non
      disclosure statement has been signed can also present an ethical dilemma for
      outbreak investigators.

PMID- 12225935
TI  - Genetic testing: ethical implications in the workplace.
AB  - The human genome project has led to impressive scientific advances in
      understanding the genetic basis of disease. To date, genetic risks associated
      with occupational illnesses are not well understood. Recent research, however,
      has uncovered an allele that appears directly related to the risk of contracting
      chronic beryllium disease; other chromosomal abnormalities have been identified
      in association with cancer. Progress from the human genome project has potential
      implications for predicting, screening, and diagnosing occupational diseases.
      Ethical issues associated with the use of genetic testing in the workplace will
      present employers, insurers, and physicians with challenging decisions related to
      promoting health in the workplace while avoiding potential misuse of sensitive
      genetic information.

PMID- 12225936
TI  - Protecting posterity: the occupational physician's ethical and legal obligations
      to pregnant workers.
AB  - This article describes Federal and international codes and laws that relate to
      protection from reproductive hazards in the workplace. Occupational health
      practitioners are advised to shift their approach from managing the technical
      aspects needed to protect individual workers to the more global approach of
      effecting policy and supporting enforcement in the realm of reproductive health.
      This broader view will not only better protect women and children but will better
      serve the interest of society in replacing all existing workers and perpetuating
      civilization for posterity.

PMID- 12225937
TI  - Ethical issues in worker productivity.
AB  - Occupational health has always operated at the intersection of corporate economic
      concerns and worker health. Conflicting demands on the loyalty of occupational
      health professionals by the interests of labor and industry have made negotiating
      this minefield an essential part of the practice of occupational medicine. In
      recent years, occupational health professionals have found themselves
      increasingly required to rationalize worker health measures with economic
      arguments. This has led to physician engagement in the realm of defining and
      measuring worker productivity. Ethical guidelines that hold worker health as a
      top priority are critical in preserving the responsibility of occupational
      physicians to their patients.

PMID- 12225938
TI  - Ethics in the locker room: the challenges for team physicians.
AB  - Team physicians act as occupational physicians in many traditional ways. However,
      they face unique ethical challenges when caring for athletes. Sports physicians
      must be cognizant of special aspects of the doctor-patient relationship, as well
      as issues related to informed consent, autonomy, and confidentiality. Conflicts
      of interest with players themselves, as well as with team management, are common.
      Team physicians must act professionally and maintain ethical principles, even in
      the high-pressure, high-performance world of athletics.

PMID- 12225939
TI  - Mental health issues: ethical considerations.
AB  - Employer-initiated psychiatric evaluations raise a number of ethical issues
      particular to mental health in the workplace. This article addresses the ethical
      concerns and potential legal implications of psychiatrist and employee role
      ambiguity (e.g., "mutual deception"); describes the elements common to
      psychiatric examinations in this setting; offers one way to provide information
      and documentation of a confidentiality waiver; reviews some differences between
      psychiatric and general medical IME evaluations; discusses interview and report
      record "ownership"; reviews dangerousness assessment strengths and limitations;
      and addresses treatment and restoration to fitness issues.

PMID- 12225940
TI  - Role of gap junctions in CO(2) chemoreception and respiratory control.
AB  - Gap junctions are composed of connexins, which are organized into intercellular
      channels that form transmembrane pathways between neurons (cell-cell coupling),
      and in some cases, neurons and glia, for exchange of ions and small molecules
      (metabolic coupling) and ionic current (electrical coupling). Cell-cell coupling
      via gap junctions has been identified in brain stem neurons that function in
      CO(2)/H(+) chemoreception and respiratory rhythmogenesis; however, the exact
      roles of gap junctions in respiratory control are undetermined. Here we review
      the methods commonly used to study gap junctions in the mammalian brain stem
      under in vitro and in vivo conditions and briefly summarize the anatomical,
      pharmacological, and electrophysiological evidence to date supporting roles for
      cell-cell coupling in respiratory rhythmogenesis and central chemoreception.
      Specific research questions related to the role of gap junctions in respiratory
      control are suggested for future research.

PMID- 12225941
TI  - Oxygen-dependent signaling in pulmonary vascular smooth muscle.
AB  - The pulmonary circulation constricts in response to acute hypoxia, which is
      reversible on reexposure to oxygen. On exposure to chronic hypoxia, in addition
      to vasoconstriction, the pulmonary vasculature undergoes remodeling, resulting in
      a sustained increase in pulmonary vascular resistance that is not immediately
      reversible. Hypoxic pulmonary vasoconstriction is physiological in the fetus, and
      there are many mechanisms by which the pulmonary vasculature relaxes at birth,
      principal among which is the acute increase in oxygen. Oxygen-induced signaling
      mechanisms, which result in pulmonary vascular relaxation at birth, and the
      mechanisms by which chronic hypoxia results in pulmonary vascular remodeling in
      the fetus and adult, are being investigated. Here, the roles of cGMP-dependent
      protein kinase in oxygen-mediated signaling in fetal pulmonary vascular smooth
      muscle and the effects of chronic hypoxia on ion channel activity and smooth
      muscle function such as contraction, growth, and gene expression were discussed.

PMID- 12225942
TI  - Ventilator-induced lung injury: in vivo and in vitro mechanisms.
AB  - A lung-protective ventilator strategy significantly reduces mortality in patients
      with acute lung injury. Substantial progress has been made in understanding how
      mechanical stress can injure the lung, both in terms of alterations in barrier
      properties of the pulmonary endothelium and epithelium as well as in stimulating
      proinflammatory responses of macrophages and neutrophils.

PMID- 12225943
TI  - EB2002 Comroe lecture. Whole animal physiology redux.

PMID- 12225944
TI  - Interleukin-8: a very important chemokine of the human airway epithelium.

PMID- 12225945
TI  - Regulation of human airway epithelial cell IL-8 expression by MAP kinases.
AB  - Recent studies indicate that maximal IL-8 protein expression requires activation
      of NF-kappaB as well as activation of the MAP kinases ERK, JNK, and p38. However,
      the precise relationship between NF-kappaB transactivation and MAP kinase
      activation remains unclear. We examined the requirements of NF-kappaB, ERK, JNK,
      and p38 for TNF-alpha-induced transcription from the IL-8 promoter in a human
      bronchial epithelial cell line. Treatment with TNF-alpha induced activation of
      all three MAP kinases. Using a combination of chemical and dominant-negative
      inhibitors, we found that inhibition of NF-kappaB, ERK, and JNK, but not p38,
      each decreased TNF-alpha-induced transcription from the IL-8 promoter. Inhibition
      of JNK signaling also substantially reduced TNF-alpha-induced NF-kappaB
      transactivation, whereas inhibition of ERK and p38 had no effect. On the other
      hand, ERK was required and sufficient for TNF-alpha-induced activation of
      activator protein (AP)-1 promoter sequences, which together function as a basal
      level enhancer. JNK activation was also required for AP-1 transactivation.
      Finally, inhibition of p38 attenuated IL-8 protein abundance, suggesting that p38
      regulates IL-8 expression in a posttranscriptional manner. We conclude that, in
      human airway epithelial cells, MAP kinases may regulate IL-8 promoter activity by
      NF-kappaB-dependent (in the case of JNK) and -independent (ERK) processes, as
      well as by posttranscriptional mechanisms (p38).

PMID- 12225946
TI  - mSprouty2 inhibits FGF10-activated MAP kinase by differentially binding to
      upstream target proteins.
AB  - Murine Sprouty2 (mSpry2) is a conserved ortholog of Drosophila Sprouty, a gene
      that inhibits several tyrosine kinase receptor pathways, resulting in net
      reduction of mitogen-activated protein (MAP) kinase activation. However, the
      precise mechanism mediating mSpry2 function as a negative regulator in tyrosine
      kinase growth factor pathways that regulate diverse biological functions remains
      incompletely characterized. Fibroblast growth factor 10 (FGF10) is a key positive
      regulator of lung branching morphogenesis and induces epithelial expression of
      mSpry2 adjacent to mesenchymal sites of FGF10. Herein, we demonstrate that FGF10
      stimulation of mouse lung epithelial cells (MLE15) overexpressing mSpry2 results
      in both mSpry2 tyrosine phosphorylation and differential binding of mSpry2 to
      several key upstream target proteins in the MAP kinase-activating pathway. Thus
      FGF receptor (FGFR) activation results in increased association of mSpry2 with
      growth factor receptor-binding protein 2, suc-1-associated nuerotrophic factor
      target 2, and Raf but decreased binding to protein tyrosine phosphatase 2 and
      GTPase-activating protein 1, resulting in a net reduction of MAP kinase
      activation. mSpry2 also spatially translocates to the plasma membrane and
      intracellular membrane structures in response to FGF10 stimulation. Our data
      demonstrate novel intracellular mechanisms mediating mSpry2 function as a
      negative regulator of uncontrolled FGF-induced MAP kinase signaling.

PMID- 12225947
TI  - Activation of multiple signaling modules is critical in angiotensin IV-induced
      lung endothelial cell proliferation.
AB  - Signaling events involving angiotensin IV (ANG IV)-mediated pulmonary artery
      endothelial cell (PAEC) proliferation were examined. ANG IV significantly
      increased upstream phosphatidylinositide (PI) 3-kinase (PI3K), PI-dependent
      kinase-1 (PDK-1), extracellular signal-related kinases (ERK1/2), and protein
      kinase B-alpha/Akt (PKB-alpha) activities, as well as downstream p70 ribosomal S6
      kinase (p70S6K) activities and/or phosphorylation of these proteins. ANG IV also
      significantly increased 5-bromo-2'-deoxy-uridine incorporation into newly
      synthesized DNA in a concentration- and time-dependent manner. Pretreatment of
      cells with wortmannin and LY-294002, inhibitors of PI3K, or rapamycin, an
      inhibitor of the mammalian target of rapamycin kinase and p70S6K, diminished the
      ANG IV-mediated activation of PDK-1 and PKB-alpha as well as phosphorylation of
      p70S6K. Although an inhibitor of mitogen-activated protein kinase kinase, PD
      98059, but not rapamycin, blocked ANG IV-induced phosphorylation of ERK1/2, both
      PD-98059 and rapamycin independently caused partial reduction in ANG IV-mediated
      cell proliferation. However, simultaneous treatment with PD-98059 and rapamycin
      resulted in total inhibition of ANG IV-induced cell proliferation. These results
      demonstrate that ANG IV-induced DNA synthesis is regulated in a coordinated
      fashion involving multiple signaling modules in PAEC.

PMID- 12225948
TI  - Effect of bradykinin, TGF-beta1, IL-1beta, and hypoxia on COX-2 expression in
      pulmonary artery smooth muscle cells.
AB  - Prostanoids are major regulators of smooth muscle function that are generated by
      cyclooxygenase (COX). Here we hypothesized that cytokines and mediators that
      regulate the pulmonary circulation would alter COX expression and prostanoid
      generation in pulmonary artery smooth muscle cells. Bradykinin, transforming
      growth factor-beta1 (TGF-beta1), and interleukin-1beta (IL-1beta) increased
      inducible COX-2 expression and prostaglandin E(2) (PGE(2)) release. Transfection
      studies using a COX-2 promoter construct demonstrated that all three agents acted
      transcriptionally. Constitutive COX-1 protein expression was unchanged. The COX
      inhibitor indomethacin, the COX-2 inhibitor NS-398, the protein synthesis
      inhibitor cycloheximide, and the glucocorticoid dexamethasone abrogated the
      increased PGE(2) levels. Dexamethasone and cycloheximide prevented COX-2
      induction. Hypoxia (3% O(2)-5% CO(2)-92% N(2)) for 24 h selectively augmented TGF
      beta1-stimulated PGE(2) production and COX-2 induction but had no effect alone.
      Prolonged hypoxic culture alone for 48 and 72 h enhanced COX-2 induction and
      increased PGE(2). These studies show that a number of stimuli are capable of
      inducing COX-2 in pulmonary artery smooth muscle cells. The interaction between
      hypoxia and TGF-beta1 may be particularly relevant to pulmonary hypertension.

PMID- 12225949
TI  - A549 subclones demonstrate heterogeneity in toxicological sensitivity and
      antioxidant profile.
AB  - In A549 cell culture, significant variability was found in sensitivity to
      actinomycin D. Using limiting dilution, actinomycin D-susceptible (G4S) and 
      resistant (D3R) subclones were isolated. G4S cells were also susceptible to
      protein synthesis inhibitors, a redox cycling quinone, and an electrophile with
      concomitant activation of caspases 3 and 9. D3R cells were resistant to these
      agents without caspase activation. Antioxidant profiles revealed that D3R cells
      had significantly higher glutathione and glutathione reductase activity but
      markedly lower catalase, glutathione peroxidase, and aldehyde reductase
      activities than G4S cells. Thus A549 cells contain at least two distinct
      subpopulations with respect to predisposition to cell death and antioxidant
      profile. Because sensitivities to agents and the antioxidant profile were
      inconsistent, mechanisms independent of antioxidants, including the apparent
      inability to activate caspases in D3R cells, may play an important role.
      Regardless, the results suggest that antioxidant profiles of asymmetrical cell
      populations cannot predict sensitivity to oxidants and warn that the use of
      single subclones is advisable for mechanistic studies using A549 or other
      unstable cell lines.

PMID- 12225950
TI  - Na(+)-K(+)-ATPase activity in alveolar epithelial cells increases with cyclic
      stretch.
AB  - Na(+)-K(+)-ATPase pumps (Na(+) pumps) in the alveolar epithelium create a
      transepithelial Na(+) gradient crucial to keeping fluid from the pulmonary air
      space. We hypothesized that alveolar epithelial stretch stimulates Na(+) pump
      trafficking to the basolateral membrane (BLM) and, thereby, increases overall
      Na(+) pump activity. Alveolar type II cells were isolated from Sprague-Dawley
      rats and seeded onto elastic membranes coated with fibronectin or 5-day
      conditioned extracellular matrix. After 2 days in culture, cells were uniformly
      stretched for 1 h in a custom-made device. Na(+) pump activity was subsequently
      assessed by ouabain-inhibitable uptake of (86)Rb(+), a K(+) tracer, and BLM Na(+)
      pump abundance was measured. In support of our hypothesis, cells increased Na(+)
      pump activity in a "dose-dependent" manner when stretched to 12, 25, or 37%
      change in surface area (DeltaSA), and cells stretched to 25% DeltaSA more than
      doubled Na(+) pump abundance in the BLM. Cells on 5-day matrix tolerated higher
      strain than cells on fibronectin before the onset of Na(+) pump upregulation.
      Treatment with Gd(3+), a stretch-activated channel blocker, amiloride, a Na(+)
      channel blocker, or both reduced but did not abolish stretch-induced effects.
      Sustained tonic stretch, unlike cyclic stretch, elicited no significant Na(+)
      pump response.

PMID- 12225951
TI  - Dynamics of metalloproteinase-2 and -9, TGF-beta, and uPA activities during
      normoxic vs. hyperoxic alveolarization.
AB  - The final stage of lung development, alveolarization, continues after birth in
      humans and rodents. Clinical interventions, such as oxygen therapy, in the first
      week of life can adversely impact alveolar formation. We compared alveolarization
      in the rat neonate under normal vs. hyperoxic conditions, examining gelatinase,
      transforming growth factor (TGF)-beta, and the protease urokinase-type
      plasminogen activator (uPA) activities in whole lung and cultured type II
      alveolar epithelial cells (AEC2). The dynamic induction of gelatinase, TGF-beta,
      and uPA activities seen in neonatal lungs during the first days of life was
      significantly impacted by hyperoxia. In whole lung, gelatinase and TGF-beta
      activities were increased, while uPA activity was decreased. At the level of the
      epithelium, AEC2 isolated from hyperoxic rat pups early in life secreted less
      active TGF-beta, less active gelatinases, and less active uPA than control
      neonatal AEC2. AEC2 from hyperoxic pups also expressed increased levels of
      proliferating cell nuclear antigen early in life compared with control neonatal
      AEC2, suggesting that oxygen-induced proliferation and/or repair were occurring.
      The developmental profile of neonatal lung was perturbed within a day of
      initiating oxygen treatment, suggesting that putative palliative treatments
      should be coadministered with oxygen therapy.

PMID- 12225952
TI  - The late asthmatic response is linked with increased surface tension and reduced
      surfactant protein B in mice.
AB  - Pulmonary surfactant dysfunction may significantly contribute to small airway
      obstruction during the asthmatic response, but neither its exact role nor its
      regulation is clear. Surfactant function and composition was studied in an
      Aspergillus fumigatus (Af)-induced late-phase allergic airway response in
      sensitized BALB/c mice. The peak of Af-induced airway hyperresponsiveness in
      sensitized and challenged mice 24 h after allergen provocation coincided with a
      significant fall in surface activity of the pulmonary surfactant. The underlying
      changes included time-dependent elaboration of eotaxin and IL-5 followed by
      eosinophil influx into the airways. The height of airway inflammation and
      hyperresponsiveness was preceded by release of IL-4 and marked reductions in
      surfactant protein (SP)-B, a hydrophobic surfactant protein responsible for
      maintaining low surface tension of the lining fluid of distal air spaces.
      Furthermore, intratracheal administration of IL-4 significantly inhibited SP-B,
      indicating a regulatory role of this cytokine in the surfactant biophysical
      changes. Thus surfactant dysfunction induced by an IL-4-driven SP-B deficiency
      after allergen provocation may be an important part of the late asthmatic airway
      response.

PMID- 12225953
TI  - Gamma-glutamyl transferase deficiency results in lung oxidant stress in normoxia.
AB  - gamma-Glutamyl transferase (GGT) is critical to glutathione homeostasis by
      providing substrates for glutathione synthesis. We hypothesized that loss of GGT
      would cause oxidant stress in the lung. We compared the lungs of GGT(enu1) mice,
      a genetic model of GGT deficiency, with normal mice in normoxia to study this
      hypothesis. We found GGT promoter 3 (P3) alone expressed in normal lung but GGT
      P3 plus P1, an oxidant-inducible GGT promoter, in GGT(enu1) lung. Glutathione
      content was barely decreased in GGT(enu1) lung homogenate and elevated nearly
      twofold in epithelial lining fluid, but the fraction of oxidized glutathione was
      increased three- and fourfold, respectively. Glutathione content in GGT(enu1)
      alveolar macrophages was decreased nearly sixfold, and the oxidized glutathione
      fraction was increased sevenfold. Immunohistochemical studies showed glutathione
      deficiency together with an intense signal for 3-nitrotyrosine in nonciliated
      bronchiolar epithelial (Clara) cells and expression of heme oxygenase-1 in the
      vasculature only in GGT(enu1) lung. When GGT(enu1) mice were exposed to
      hyperoxia, survival was decreased by 25% from control because of accelerated
      formation of vascular pulmonary edema, widespread oxidant stress in the
      epithelium, diffuse depletion of glutathione, and severe bronchiolar cellular
      injury. These data indicate a critical role for GGT in lung glutathione
      homeostasis and antioxidant defense in normoxia and hyperoxia.

PMID- 12225954
TI  - Depletion of pulmonary EC-SOD after exposure to hyperoxia.
AB  - Extracellular superoxide dismutase (EC-SOD) is highly expressed in lung tissue.
      EC-SOD contains a heparin-binding domain that is sensitive to proteolysis. This
      heparin-binding domain is important in allowing EC-SOD to exist in relatively
      high concentrations in specific regions of the extracellular matrix and on cell
      surfaces. EC-SOD has been shown to protect the lung against hyperoxia in
      transgenic and knockout studies. This study tests the hypothesis that proteolytic
      clearance of EC-SOD from the lung during hyperoxia contributes to the oxidant
      antioxidant imbalance that is associated with this injury. Exposure to 100%
      oxygen for 72 h resulted in a significant decrease in EC-SOD levels in the lungs
      and bronchoalveolar lavage fluid of mice. This correlated with a significant
      depletion of EC-SOD from the alveolar parenchyma as determined by
      immunofluorescence and immunohistochemistry. EC-SOD mRNA was unaffected by
      hyperoxia; however, there was an increase in the ratio of proteolyzed to uncut EC
      SOD after hyperoxia, which suggests that hyperoxia depletes EC-SOD from the
      alveolar parenchyma by cutting the heparin-binding domain. This may enhance
      hyperoxic pulmonary injury by altering the oxidant-antioxidant balance in
      alveolar spaces.

PMID- 12225955
TI  - Meconium aspiration produces airway hyperresponsiveness and eosinophilic
      inflammation in a murine model.
AB  - Meconium aspiration syndrome is a cause of significant morbidity and mortality in
      the perinatal period and has been implicated in the pathogenesis of airway
      dysfunction. In this study, we developed a murine model to evaluate the effects
      of meconium aspiration on airway physiology and lung cellular responses. Under
      light anesthesia, BALB/c mice received a single intratracheal instillation of
      meconium or physiological saline. Respiratory mechanics were measured in
      unrestrained animals and expressed as percent increase in enhanced pause to
      increasing concentrations of methacholine (MCh). Furthermore, we assessed the
      changes in cells and cytokines into the bronchoalveolar lavage fluid (BALF). We
      found meconium aspiration produced increased airway responsiveness to MCh at 7
      days. These functional changes were associated with lymphocytic/eosinophilic
      inflammation, goblet cell metaplasia, and increased concentrations of IL-5 and IL
      13 in the BALF. Our findings suggest meconium aspiration leads to alterations of
      airway function, lung eosinophilia, goblet cell metaplasia, and cytokine
      imbalance, thus providing the first evidence of meconium-induced airway
      dysfunction in a mouse model.

PMID- 12225956
TI  - Oxidative stress activates anion exchange protein 2 and AP-1 in airway epithelial
      cells.
AB  - Anion exchange protein 2 (AE2) is a membrane-bound protein that mediates chloride
      bicarbonate exchange. In addition to regulating intracellular pH and cell volume,
      AE2 exports superoxide (O.) to the extracellular matrix in an HCO-dependent
      process. Given this ability to export O., we hypothesized that expression of AE2
      in the lung is regulated by oxidative stress. AE2 mRNA and protein expression was
      measured by RT-PCR and Western blot analysis, respectively, in differentiated
      human bronchial epithelial cells exposed to H(2)O(2) (100 microM). Alterations in
      in vivo AE2 protein expression were evaluated in lung tissue of rats exposed to
      70% O(2). The role of transcription factor activator protein (AP)-1 in oxidant
      regulation of AE2 was evaluated by EMSA and by immunoblotting of nuclear phospho
      c-jun. Results show increased AE2 mRNA and protein expression after oxidant
      exposure. This was preceded by transient increases in DNA binding of AE2-specific
      AP-1 and phosphorylation of c-jun. This study demonstrates that AE2 expression is
      regulated by oxidative stress in airway epithelial cells and that this regulation
      correlates with activation of AP-1.

PMID- 12225957
TI  - Alveolar macrophage activation after trauma-hemorrhage and sepsis is dependent on
      NF-kappaB and MAPK/ERK mechanisms.
AB  - The acute respiratory distress syndrome (ARDS) is a major cause of morbidity
      after injury. We hypothesized that alveolar macrophage (AMPhi) chemokine and
      cytokine release after hemorrhage and sepsis is regulated by NF-kappaB and MAPK.
      Adult male rats underwent soft tissue trauma and hemorrhagic shock (~90 min)
      followed by crystalloid resuscitation. Sepsis was induced by cecal ligation and
      puncture (CLP) 20 h after resuscitation. AMPhi were harvested, and TNF-alpha, IL
      6, and macrophage inflammatory protein (MIP)-2 release and serum IL-6 and TNF
      alpha levels were measured at 5 h after HCLP. Lung tissues were analyzed for
      activation of NF-kappaB, myeloperoxidase activity, and wet/dry weight ratio. In
      control animals, AMPhi were stimulated with LPS with or without inhibitors of NF
      kappaB and MAPK. Serum TNF-alpha and IL-6 levels and spontaneous AMPhi TNF-alpha
      and MIP-2 release were elevated (P < 0.05) after HCLP, concomitantly with the
      development of lung edema and leukocyte activation. Activation of NF-kappaB
      increased in lungs from the hemorrhage and CLP group compared with shams.
      Inhibition of NF-kappaB or the upstream MAPK significantly decreased LPS
      stimulated AMPhi activation. Because enhanced release of inflammatory mediators
      by AMPhi may contribute to ARDS after severe trauma, inhibition of intracellular
      signaling pathways represents a target to attenuate organ injury under those
      conditions.

PMID- 12225958
TI  - Proteoglycan expression in bleomycin lung fibroblasts: role of transforming
      growth factor-beta(1) and interferon-gamma.
AB  - Bleomycin (BM)-induced pulmonary fibrosis involves excess production of
      proteoglycans (PGs). Because transforming growth factor-beta(1) (TGF-beta(1))
      promotes fibrosis, and interferon-gamma (IFN-gamma) inhibits it, we hypothesized
      that TGF-beta(1) treatment would upregulate PG production in fibrotic lung
      fibroblasts, and IFN-gamma would abrogate this effect. Primary lung fibroblast
      cultures were established from rats 14 days after intratracheal instillation of
      saline (control) or BM (1.5 units). PGs were extracted and subjected to Western
      blot analysis. Bleomycin-exposed lung fibroblasts (BLF) exhibited increased
      production of versican (VS), heparan sulfate proteoglycan (HSPG), and biglycan
      (BG) compared with normal lung fibroblasts (NLF). Compared with NLF, BLF released
      significantly increased amounts of TGF-beta(1). TGF-beta(1) (5 ng/ml for 48 h)
      upregulated PG expression in both BLF and NLF. Incubation of BLF with anti-TGF
      beta antibody (1, 5, and 10 microg/ml) inhibited PG expression in a dose
      dependent manner. Treatment of BLF with IFN-gamma (500 U. ml(-1) x 48 h) reduced
      VS, HSPG, and BG expression. Furthermore, IFN-gamma inhibited TGF-beta(1)-induced
      increases in PG expression by these fibroblasts. Activation of fibroblasts by TGF
      beta(1) promotes abnormal deposition of PGs in fibrotic lungs; downregulation of
      TGF-beta(1) by IFN-gamma may have potential therapeutic benefits in this disease.

PMID- 12225959
TI  - Mitogen-activated protein kinases regulate HO-1 gene transcription after ischemia
      reperfusion lung injury.
AB  - Lung ischemia-reperfusion (I-R) is an important model of oxidant-mediated acute
      lung and vascular injury. Heme oxygenase-1 (HO-1) is a cytoprotective gene that
      is markedly induced by lung I-R injury. HO-1 mRNA is increased in mouse lung
      after 30 min of lung hilar clamping (ischemia) followed by 2-6 h of unclamping
      (reperfusion) compared with control mice. In a variety of vascular cell types, HO
      1 mRNA is induced after 24 h of anoxia followed by 30 min-1 h of reoxygenation (A
      R). Transfection studies reveal that the promoter and 5'-distal enhancer E1 are
      necessary and sufficient for increased HO-1 gene transcription after A-R.
      Immunoblotting studies show all three subfamilies of MAPKs (ERK, JNK, and p38)
      are activated by 15 min of reperfusion. We also demonstrate that HO-1 gene
      transcription after A-R involves ERK, JNK, and p38 MAPK pathways. Together, our
      data show that I-R not only induces HO-1 gene expression in mouse lungs and
      vascular cells but that gene transcription occurs via the promoter and E1
      enhancer and involves upstream MAPK pathways.

PMID- 12225960
TI  - Rho protein inactivation induced apoptosis of cultured human endothelial cells.
AB  - Small GTP-binding Rho GTPases regulate important signaling pathways in
      endothelial cells, but little is known about their role in endothelial cell
      apoptosis. Clostridial cytotoxins specifically inactivate GTPases by
      glucosylation [Clostridium difficile toxin B-10463 (TcdB-10463), C. difficile
      toxin B-1470 (TcdB-1470)] or ADP ribosylation (C. botulinum C3 toxin). Exposure
      of human umbilical cord vein endothelial cells (HUVEC) to TcdB-10463, which
      inhibits RhoA/Rac1/Cdc42, or to C3 toxin, which inhibits RhoA, -B, -C, resulted
      in apoptosis, whereas inactivation of Rac1/Cdc42 with TcdB-1470 was without
      effect, suggesting that Rho inhibition was responsible for endothelial apoptosis.
      Disruption of endothelial microfilaments as well as inhibition of p160ROCK did
      not induce endothelial apoptosis. Exposure to TcdB-10463 resulted in activation
      of caspase-9 and -3 but not caspase-8 in HUVEC. Moreover, Rho inhibition reduced
      expression of antiapoptotic Bcl-2 and Mcl-1 and increased proapoptotic Bid but
      had no effect on Bax or FLIP protein levels. Caspase-3 activity and apoptosis
      induced by TcdB-10463 were abolished by cAMP elevation. In summary, inhibition of
      Rho in endothelial cells activates caspase-9- and -3-dependent apoptosis, which
      can be antagonized by cAMP elevation.

PMID- 12225961
TI  - Postnatal maturation in nitric oxide-induced pulmonary artery relaxation
      involving cyclooxygenase-1 activity.
AB  - The maturation in the vasodilator response to nitric oxide (NO) in isolated
      intrapulmonary arteries was analyzed in newborns and 15- to 20-day-old piglets.
      The vasodilator responses to NO gas but not to the NO donor sodium nitroprusside
      increased with age. The inhibitory effects of the superoxide dismutase inhibitor
      diethyldithiocarbamate and xanthine oxidase plus hypoxanthine and the
      potentiation induced by superoxide dismutase and MnCl(2) of NO-induced
      vasodilatation were similar in the two age groups. Diphenyleneiodonium (NADPH
      oxidase inhibitor) potentiated the response to NO, and this effect was more
      pronounced in the older animals. The nonselective cyclooxygenase inhibitors
      indomethacin and meclofenamate and the preferential cyclooxygenase-1 inhibitor
      aspirin augmented NO-induced relaxation specifically in newborns, whereas the
      selective cycloxygenase-2 inhibitor NS-398 had no effect. The expressions of
      alpha-actin, cycloxygenase-1, and cycloxygenase-2 proteins were similar, whereas
      Cu,Zn-superoxide dismutase decreased with age. Therefore, the present data
      suggest that the maturational increase in the vasodilatation of NO in the
      pulmonary arteries during the first days of extrauterine life involves a
      cycloxygenase-dependent inhibition of neonatal NO activity.

PMID- 12225962
TI  - Inhibition of proteasome activity is involved in cobalt-induced apoptosis of
      human alveolar macrophages.
AB  - Inhalation of particulate cobalt has been known to induce interstitial lung
      disease. There is growing evidence that apoptosis plays a crucial role in
      physiological and pathological settings and that the ubiquitin-proteasome system
      is involved in the regulation of apoptosis. Cadmium, the same transitional heavy
      metal as cobalt, has been reported to accumulate ubiquitinated proteins in
      neuronal cells. On the basis of these findings, we hypothesized that cobalt would
      induce apoptosis in the lung by disturbance of the ubiquitin-proteasome pathway.
      To evaluate this, we exposed U-937 cells and human alveolar macrophages (AMs) to
      cobalt chloride (CoCl(2)) and examined their apoptosis by DNA fragmentation
      assay, 4',6-diamidino-2'-phenylindol dihydrochloride staining, and Western blot
      analysis. CoCl(2) induced apoptosis and accumulated ubiquitinated proteins.
      Exposure to CoCl(2) inhibited proteasome activity in U-937 cells. Cobalt-induced
      apoptosis was mediated via mitochondrial pathway because CoCl(2) released
      cytochrome c from mitochondria. These results suggest that cobalt-induced
      apoptosis of AMs may be one of the mechanisms for cobalt-induced lung injury and
      that the accumulation of ubiquitinated proteins might be involved in this
      apoptotic process.

PMID- 12225963
TI  - Evidence for the role of p38 MAP kinase in hypoxia-induced pulmonary
      vasoconstriction.
AB  - Mitogen-activated protein (MAP) kinases regulate smooth muscle cell contraction.
      Hypoxia contracts pulmonary arteries by mechanisms that are incompletely
      understood. We hypothesized that hypoxic contraction of pulmonary arteries
      involves activation of the MAP kinases. To test this hypothesis, we studied the
      effects of SB-202190, a p38 MAP kinase inhibitor, PD-98059 and UO-126, two
      structurally different MEKK inhibitors, and anisomycin, a stimulator of p38 MAP
      kinase on acute hypoxia-induced contraction in rat conduit pulmonary artery rings
      precontracted with phenylephrine or KCl. Hypoxia induced a transient contraction,
      followed by a relaxation, and then a slowly developing sustained contraction.
      Hypoxia also significantly increased phosphorylation of p38 MAP kinase. SB-202190
      did not affect the transient phase but abrogated the sustained phase of hypoxic
      contraction, whereas anisomycin enhanced both phases of contraction. SB-202190
      also attenuated and anisomycin enhanced the phenylephrine-induced contraction. In
      contrast, PD-98059 and UO-126 had minimal effects on either hypoxic or
      phenylephrine-induced contraction. None of the treatments modified KCl-induced
      contraction. We conclude that p38, but not the ERK1/ERK2 MAP kinase pathway,
      mediates the sustained phase of hypoxic contraction in isolated rat pulmonary
      arteries.

PMID- 12225965
TI  - Fish oil slows S phase progression and may cause upstream shift of DHFR
      replication origin ori-beta in CHO cells.
AB  - Fish oils (FOs) have been noted to reduce growth and proliferation of certain
      tumor cells, effects usually attributed to the content of polyunsaturated fatty
      acids of the n-3 family, which are thought to modulate cellular signaling
      pathways. We investigated the influence of FO on cell cycle kinetics of cultured
      Chinese hamster ovary cells. Exponentially growing cells were labeled with 5
      bromo-2'-deoxyuridine (BrdU) and analyzed by flow cytometry after 5-day treatment
      with exogenous fat. Bivariate BrdU-DNA analysis indicated slower progression
      through S phase and thus longer S phase duration time in FO- but not corn oil
      treated or control cells. We hypothesize that FO treatment might interfere with
      spatial/temporal organization of replication origins. Therefore, we mapped the
      well-characterized replication origin ori-beta downstream of the dihydrofolate
      reductase gene with the nascent strand length assay. Three DNA marker segments
      with known positions relative to this origin were amplified by PCR. By
      quantitatively assessing DNA length of the fragments in all fractions containing
      these markers, the location of ori-beta was established. In control or corn oil
      treated cells, the location of ori-beta was consistent with previous studies.
      However, in FO-treated cells, DNA replication appears to start from a new site
      located farther upstream from ori-beta, suggesting a different replication
      initiation pattern. This study suggests novel mechanism(s) by which fats affect
      cell proliferation and DNA replication in mammalian cells.

PMID- 12225964
TI  - Alveolar macrophage-mediated elastolysis: roles of matrix metalloproteinases,
      cysteine, and serine proteases.
AB  - Chronic obstructive pulmonary disease (COPD) is a common lung disease with
      cigarette smoking as the major etiological factor, but only 15% of smokers
      develop COPD. Destruction of lung elastin observed in COPD is mediated by many
      enzymes, including cysteine, serine, and matrix metalloproteinases (MMP). The
      contribution of these enzymes to the lung elastolytic load, released from
      alveolar macrophages collected from nonsmokers, healthy smokers, and COPD
      patients, was examined by radiolabeled elastin as substrate in the presence of
      specific enzyme inhibitors. The activity of MMP was further examined by
      zymography and Western blotting. COPD macrophages degraded more elastin than
      either of the other groups. Elastolysis was greatest in the initial 24 h. Through
      the 72-h culture period, the contribution to elastolysis of serine elastases
      decreased, MMP increased, and cysteine elastases remained constant. The increased
      release of elastolytic enzymes in COPD subjects may explain why some smokers
      develop COPD. This difference may be due to unknown susceptibility factors.
      Serine proteases play a significant role; however, other enzymes, particularly
      the MMP, deserve further investigation.

PMID- 12225966
TI  - Duality of G protein-coupled mechanisms for beta-adrenergic activation of NKCC
      activity in skeletal muscle.
AB  - Skeletal muscle Na(+)-K(+)-2Cl(-) cotransporter (NKCC) activity provides a
      potential mechanism for regulated K(+) uptake. beta-Adrenergic receptor (beta-AR)
      activation stimulates skeletal muscle NKCC activity in a MAPK pathway-dependent
      manner. We examined potential G protein-coupled pathways for beta-AR-stimulated
      NKCC activity. Inhibition of G(s)-coupled PKA blocked isoproterenol-stimulated
      NKCC activity in both the slow-twitch soleus muscle and the fast-twitch plantaris
      muscle. However, the PKA-activating agents cholera toxin, forskolin, and 8-bromo
      cAMP (8-BrcAMP) were not sufficient to activate NKCC in the plantaris and
      partially stimulated NKCC activity in the soleus. Isoproterenol-stimulated NKCC
      activity in the soleus was abolished by pretreatment with pertussis toxin (PTX),
      indicating a G(i)-coupled mechanism. PTX did not affect the 8-BrcAMP-stimulated
      NKCC activity. PTX treatment also precluded the isoproterenol-mediated ERK1/2
      MAPK phosphorylation in the soleus, consistent with NKCC's MAPK dependency.
      Inhibition of isoproterenol-stimulated ERK activity by PTX treatment was
      associated with an increase in Akt activation and phosphorylation of Raf-1 on the
      inhibitory residue Ser(259). These results demonstrate a novel, muscle phenotype
      dependent mechanism for beta-AR-mediated NKCC activation that involves both G(s)
      and G(i) protein-coupled mechanisms.

PMID- 12225967
TI  - Functional and molecular evidence for Na(+)-HCO cotransporter in porcine vas
      deferens epithelia.
AB  - This study focused on the role of sodium-bicarbonate cotransporter (NBC1) in cAMP
      stimulated ion transport in porcine vas deferens epithelium. Ion substitution
      experiments in modified Ussing chambers revealed that cAMP-mediated stimulation
      was dependent on the presence of Na(+), HCO, and Cl(-) for a full response. HCO
      dependent current was unaffected by acetazolamide, bumetanide, or amiloride but
      was inhibited by basolateral 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid.
      Na(+)-driven, HCO-dependent, stilbene-inhibitable anion flux was observed across
      the basolateral membrane of selectively permeabilized monolayers. Results of
      radiotracer flux studies suggest a 4,4'-dinitrostilbene-2,2'-disulfonate
      sensitive stoichiometry of 2 base equivalents per Na(+). Antibodies raised
      against rat kidney NBC epitopes (rkNBC; amino acids 338-391 and 928-1035)
      identified a single band of ~145 kDa. RT-PCR detected NBC1 message in porcine vas
      deferens epithelia. These results demonstrate that vas deferens epithelial cells
      possess the proteins necessary for the vectoral transport of HCO and that these
      mechanisms are maintained in primary culture. Taken together, the results
      indicate that vas deferens epithelia play an active role in male fertility and
      have implications for our understanding of the relationship between cystic
      fibrosis and congenital bilateral absence of the vas deferens.

PMID- 12225968
TI  - Characterization of a voltage-dependent Na(+) current in human esophageal smooth
      muscle.
AB  - Smooth muscle contraction is critical to peristalsis in the human esophagus, yet
      the nature of the channels mediating excitation remains to be elucidated. The
      objective of this study was to characterize the inward currents in human
      esophageal smooth muscle cells (HESMCs). Esophageal tissue was isolated from
      patients undergoing surgery for cancer and grown in primary culture, and currents
      were recorded using patch-clamp electrophysiology. Depolarization elicited inward
      current activating positive to -40 mV and peaking at 0 mV and consisting of
      transient and sustained components. The transient current was half activated at 
      16 mV and half inactivated at -67 mV. The transient current was abolished by
      removal of bath Na(+) or application of TTX (IC(50) ~20 nM), whereas it persisted
      in the absence of bath Ca(2+) or the presence of Cd(2+). These data provide
      evidence that cultured HESMCs express voltage-dependent Na(+) channels. RT-PCR
      revealed mRNA transcripts for Na(x), the "atypical" Na(+) channel isoform, as
      well as Na(v)1.4. These studies provide the first evidence of Na(v)1.4 in smooth
      muscle and contribute to a model of excitation in HESMCs.

PMID- 12225969
TI  - TSH signaling and cell survival in 3T3-L1 preadipocytes.
AB  - Thyroid-stimulating hormone (TSH) action in adipose tissue remains largely
      unknown. Our previous work indicates that human preadipocytes express functional
      TSH receptor (TSHR) protein, demonstrated by TSH activation of p70 S6 kinase (p70
      S6K). We have now studied murine 3T3-L1 preadipocytes to further characterize TSH
      signaling and cellular action. Western blot analysis of 3T3-L1 preadipocyte
      lysate revealed the 100-kDa mature processed form of TSHR. TSH activated p70 S6K
      and protein kinase B (PKB/Akt), as measured by immunoblot analysis. Preincubation
      with wortmannin or LY-294002 completely blocked TSH activation of p70 S6K and
      PKB/Akt, implicating phosphoinositide 3-kinase (PI3K) in their regulation. TSH
      increased phosphotyrosine protein(s) in the 125-kDa region and augmented the
      associated PI3K activity fourfold. TSH had no effect on cAMP levels in 3T3-L1
      preadipocytes, suggesting that adenylyl cyclase is not involved in TSH activation
      of the PI3K-PKB/Akt-p70 S6K pathway. 3T3-L1 preadipocyte cell death was reduced
      by 29-76% in serum-deprived (6 h) preadipocytes treated with 1-20 microM TSH. In
      the presence of 20 microM TSH, an 88% reduction in terminal deoxynucleotidyl
      transferase (TdT)-mediated dUTP nick end labeling (TUNEL)-positive cells was
      observed in serum-starved (3 h) 3T3-L1 preadipocytes as well as a 93% reduction
      in the level of cleaved activated caspase 3. In summary, TSH acts as a survival
      factor in 3T3-L1 preadipocytes. TSH does not stimulate cAMP accumulation in these
      cells but instead activates a PI3K-PKB/Akt-p70 S6K pathway.

PMID- 12225970
TI  - USF-1 and USF-2 trans-repress IL-1beta-induced iNOS transcription in mesangial
      cells.
AB  - Transcriptional activation of the inducible nitric oxide synthase (iNOS) gene
      requires multiple interactions of cis elements and trans-acting factors. Previous
      in vivo footprinting studies (Goldring CE, Reveneau S, Algarte M, and Jeannin JF.
      Nucleic Acids Res 24: 1682-1687, 1996) of the murine iNOS gene demonstrated
      lipopolysaccharide-inducible protection of guanines in the region -904/-883,
      which includes an E-box motif. In this report, by using site-directed mutagenesis
      of the -893/-888 E-box and correlating functional assays of the mutated iNOS
      promoter with upstream stimulatory factor (USF) DNA-binding activities, we
      demonstrate that the -893/-888 E-box motif is functionally required for iNOS
      regulation in murine mesangial cells and that USFs are in vivo components of the
      iNOS transcriptional response complex. Mutation of the E-box sequence augmented
      the iNOS response to interleukin-1beta (IL-1beta) in transiently transfected
      mesangial cells. Gel mobility shift assays demonstrated that USFs cannot bind to
      the -893/-888 E-box promoter region when the E-box is mutated. Cotransfection of
      USF-1 and USF-2 expression vectors with iNOS promoter-luciferase reporter
      constructs suppressed IL-1beta-simulated iNOS promoter activity. Cotransfection
      of dominant-negative USF-2 mutants lacking the DNA binding domain or cis-element
      decoys containing concatamers of the -904/-883 region augmented IL-1beta
      stimulation of iNOS promoter activity. Gel mobility shift assays showed that only
      USF-1 and USF-2 supershifted the USF protein-DNA complexes. These results
      demonstrated that USF binding to the E-box at -893/-888 serves to trans-repress
      basal expression and IL-1beta induction of the iNOS promoter.

PMID- 12225971
TI  - Peroxisome proliferators compete and ameliorate Hcy-mediated endocardial
      endothelial cell activation.
AB  - To determine whether homocysteine (Hcy)-mediated activation of endocardial
      endothelial (EE) cells is ameliorated by peroxisome proliferator-activated
      receptor (PPAR), we isolated EE cells from mouse endocardium. Matrix
      metalloproteinase (MMP) activity and intercellular adhesion molecule (ICAM)-1 in
      EE cells were measured in the presence and absence of Hcy, and ciprofibrate (CF;
      PPAR-alpha agonist) or 15-deoxy-Delta(12,14)-prostaglandin J(2) (PGJ(2); PPAR
      gamma agonist) by zymography and Western blot analyses, respectively. Results
      suggest that Hcy-mediated MMP activation and ICAM-1 expression are ameliorated by
      CF and PGJ(2). To test the hypothesis that Hcy competes with other ligands for
      binding to PPARalpha and -gamma, we prepared cardiac nuclear extracts. Extracts
      were loaded onto an Hcy-cellulose affinity column. Bound proteins were eluted
      with CF and PGJ(2). To determine conformational changes in PPAR upon binding to
      Hcy, we measured PPAR fluorescence at 334 nm. Dose-dependent increase in PPAR
      fluorescence demonstrated a primary binding affinity of 0.32 +/- 0.06 microM.
      There was dose-dependent quenching of PPAR fluorescence by fluorescamine
      homocysteine (F-Hcy). PPAR-alpha fluorescence quenching was abrogated by the
      addition of CF but not by PGJ(2). PPAR-gamma fluorescence quenching was abrogated
      by the addition of PGJ(2) but not by CF. These results suggest that Hcy competes
      with CF and PGJ(2) for binding to PPAR-alpha and -gamma, respectively, indicating
      a role of PPAR in amelioration of Hcy-mediated EE dysfunction.

PMID- 12225972
TI  - NO upregulation of a cyclic nucleotide-gated channel contributes to calcium
      elevation in endothelial cells.
AB  - We investigated whether nitric oxide (NO) upregulates a cyclic nucleotide-gated
      (CNG) channel and whether this contributes to sustained elevation of
      intracellular calcium levels ([Ca(2+)](i)) in porcine pulmonary artery
      endothelial cells (PAEC). Exposure of PAEC to an NO donor, NOC-18 (1 mM), for 18
      h increased the protein and mRNA levels of CNGA2 40 and 50%, respectively (P <
      0.05). [Ca(2+)](i) in NO-treated cells was increased 50%, and this increase was
      maintained for up to 12 h after removal of NOC-18 from medium. Extracellular
      calcium is required for the increase in [Ca(2+)](i) in NO-treated cells.
      Thapsigargin induced a rapid cytosolic calcium rise, whereas both a CNG and a
      nonselective cation channel blocker caused a faster decline in [Ca(2+)](i),
      suggesting that capacitive calcium entry contributes to the elevated calcium
      levels. Antisense inhibition of CNGA2 expression attenuated the NO-induced
      increases in CNGA2 expression and [Ca(2+)](i) and in capacitive calcium entry.
      Our results demonstrate that exogenous NO upregulates CNGA2 expression and that
      this is associated with elevated [Ca(2+)](i) and capacitive calcium entry in
      porcine PAEC.

PMID- 12225973
TI  - Fast-twitch skeletal muscles of dystrophic mouse pups are resistant to injury
      from acute mechanical stress.
AB  - Loss of the dystrophin-glycoprotein complex from muscle sarcolemma in Duchenne's
      muscular dystrophy (DMD) renders the membrane susceptible to mechanical injury,
      leaky to Ca(2+), and disrupts signaling, but the precise mechanism(s) leading to
      the onset of DMD remain unclear. To assess the role of mechanical injury in the
      onset of DMD, extensor digitorum longus (EDL) muscles from C57 (control), mdx,
      and mdx-utrophin-deficient [mdx:utrn(-/-); dystrophic] pups aged 9-12 days were
      subjected to an acute stretch-injury or no-stretch protocol in vitro. Before the
      stretches, isometric stress was attenuated for mdx:utrn(-/-) compared with
      control muscles at all stimulation frequencies (P < 0.05). During the stretches,
      EDL muscles for each genotype demonstrated similar mean stiffness values. After
      the stretches, isometric stress during a tetanus was decreased significantly for
      both mdx and mdx:utrn(-/-) muscles compared with control muscles (P < 0.05).
      Membrane injury assessed by uptake of procion orange dye was greater for
      dystrophic compared with control EDL (P < 0.05), but, within each genotype, the
      percentage of total cells taking up dye was not different for the no-stretch vs.
      stretch condition. These data suggest that the sarcolemma of maturing dystrophic
      EDL muscles are resistant to acute mechanical injury.

PMID- 12225974
TI  - Presence of the M-type sPLA(2) receptor on neutrophils and its role in elastase
      release and adhesion.
AB  - Secretory phospholipase A(2) (sPLA(2)) produces lipids that stimulate
      polymorphonuclear neutrophils (PMNs). With the discovery of sPLA(2) receptors
      (sPLA(2)-R), we hypothesize that sPLA(2) stimulates PMNs through a receptor.
      Scatchard analysis was used to determine the presence of a sPLA(2) ligand.
      Lysates were probed with an antibody to the M-type sPLA(2)-R, and the
      immunoreactivity was localized. PMNs were treated with active and inactive
      (+EGTA) sPLA(2) (1-100 units of enzyme activity/ml, types IA, IB, and IIA), and
      elastase release and PMN adhesion were measured. PMNs incubated with inactive,
      FITC-linked sPLA(2)-IB, but not sPLA(2)-IA, demonstrated the presence of a
      sPLA(2)-R with saturation at 2.77 fM and a K(d) of 167 pM. sPLA(2)-R
      immunoreactivity was present at 185 kDa and localized to the membrane. Inactive
      sPLA(2)-IB activated p38 MAPK, and p38 MAPK inhibition attenuated elastase
      release. Active sPLA(2)-IA caused elastase release, but inactive type IA did not.
      sPLA(2)-IB stimulated elastase release independent of activity; inactive sPLA(2)
      IIA partially stimulated PMNs. sPLA(2)-IB and sPLA(2)-IIA caused PMN adhesion. We
      conclude that PMNs contain a membrane M-type sPLA(2)-R that activates p38 MAPK.

PMID- 12225975
TI  - Two pore residues mediate acidosis-induced enhancement of C-type inactivation of
      the Kv1.4 K(+) channel.
AB  - Acidosis inhibits current through the Kv1.4 K(+) channel, perhaps as a result of
      enhancement of C-type inactivation. The mechanism of action of acidosis on C-type
      inactivation has been studied. A mutant Kv1.4 channel that lacks N-type
      inactivation (fKv1.4 Delta2-146) was expressed in Xenopus oocytes, and currents
      were recorded using two-microelectrode voltage clamp. Acidosis increased fKv1.4
      Delta2-146 C-type inactivation. Replacement of a pore histidine with cysteine
      (H508C) abolished the increase. Application of positively charged thiol-specific
      methanethiosulfonate to fKv1.4 Delta2-146 H508C increased C-type inactivation,
      mimicking the effect of acidosis. Replacement of a pore lysine with cysteine
      (K532C) abolished the acidosis-induced increase of C-type inactivation. A model
      of the Kv1.4 pore, based on the crystal structure of KcsA, shows that H508 and
      K532 lie close together. It is suggested that the acidosis-induced increase of C
      type inactivation involves the charge on H508 and K532.

PMID- 12225976
TI  - Role of PKCalpha in feedback regulation of Na(+) transport in an electrically
      tight epithelium.
AB  - It has long been known that Na(+) channels in electrically tight epithelia are
      regulated by homeostatic mechanisms that maintain a steady state and allow new
      levels of transport to be sustained in hormonally challenged cells. Little is
      known about the potential pathways involved in these processes. In addition to
      short-term effect, recent evidence also indicates the involvement of PKC in the
      long-term regulation of the epithelial Na(+) channel (ENaC) at the protein level
      (40). To determine whether stimulation of ENaC involves feedback regulation of
      PKC levels, we utilized Western blot analysis to determine the distribution of
      PKC isoforms in polarized A6 epithelia. We found the presence of PKC isoforms in
      the conventional (alpha and gamma), novel (delta, eta, and epsilon), and atypical
      (iota, lambda, and zeta) groups. Steady-state stimulation of Na(+) transport with
      aldosterone was accompanied by a specific decrease of PKCalpha protein levels in
      both the cytoplasmic and membrane fractions. Similarly, overnight treatment with
      an uncharged amiloride analog (CDPC), a procedure that through feedback
      regulation causes a stimulation of Na(+) transport, also decreased PKCalpha
      levels. These effects were additive, indicating separate mechanisms that converge
      at the level of PKCalpha. These effects were not accompanied by changes of
      PKCalpha mRNA levels as determined by Northern blot analysis. We propose that
      this may represent a novel regulatory feedback mechanism necessary for sustaining
      an increase of Na(+) transport.

PMID- 12225977
TI  - Fluid shear- and time-dependent modulation of molecular interactions between PMNs
      and colon carcinomas.
AB  - This study compares the effects of fluid shear on the kinetics, adhesion
      efficiency, stability, and molecular requirements of polymorphonuclear leukocyte
      (PMN) binding to two colon adenocarcinoma cell-lines, the CD54-negative/sLe(x)
      bearing LS174T cells and the CD54-expressing/sLe(x)-low HCT-8 cells. The
      efficiency of PMN-colon carcinoma heteroaggregation decreases with increasing
      shear, with PMNs binding HCT-8 more efficiently than LS174T cells at low shear
      (50-200 s(-1)). In the low shear regime, CD11b is sufficient to mediate PMN
      binding to LS174T cells. In contrast, both CD11a and CD11b contribute to PMN-HCT
      8 heteroaggregation, with CD54 on HCT-8 cells acting as a CD11a ligand at early
      time points. At high shear, only PMN-LS174T heteroaggregation occurs, which is
      initiated by PMN L-selectin binding to a sialylated, O-linked, protease-sensitive
      ligand on LS174T cells. PMN-LS174T heteroaggregation is primarily dependent on
      the intercellular contact duration (or shear rate), whereas PMN-HCT-8 binding is
      a function of both the intercellular contact duration and the applied force (or
      shear stress). Cumulatively, these studies suggest that fluid shear modulates the
      kinetics and molecular mechanisms of PMN-colon carcinoma cell aggregation.

PMID- 12225978
TI  - Urate/alpha-ketoglutarate exchange in avian basolateral membrane vesicles.
AB  - Membrane transport pathways for transcellular secretion of urate across the
      proximal tubule were investigated in avian kidney. The presence of coupled
      urate/alpha-ketoglutarate exchange was investigated in basolateral membrane
      vesicles (BLMV) by [(14)C]urate and [alpha-(3)H]ketoglutarate flux measurements.
      An inward Na gradient induced accumulation of alpha-ketoglutarate of sufficient
      magnitude to suggest a Na-dicarboxylate cotransporter. An inward Na gradient also
      induced concentrative accumulation of urate in the presence of alpha
      ketoglutarate but not in its absence, suggesting urate/alpha-ketoglutarate
      exchange. alpha-Ketoglutarate-dependent stimulation of urate uptake was not
      observed in brush-border membrane vesicles. An outward urate gradient induced
      concentrative accumulation of alpha-ketoglutarate. alpha-Ketoglutarate-coupled
      urate uptake was specific for alpha-ketoglutarate, Cl dependent, and insensitive
      to membrane potential. alpha-Ketoglutarate-coupled urate uptake was inhibited by
      increasing p-aminohippurate (PAH) concentrations, and alpha-ketoglutarate-coupled
      PAH uptake was observed. alpha-Ketoglutarate-coupled PAH uptake was inhibited by
      increasing urate concentrations, and an outward urate gradient induced
      concentrative accumulation of PAH. These results suggest a Cl-dependent, alpha
      ketoglutarate-coupled anion exchange mechanism as a pathway for active urate
      uptake across the basolateral membrane of urate-secreting proximal tubule cells.

PMID- 12225979
TI  - Facilitated diffusion of urate in avian brush-border membrane vesicles.
AB  - Membrane transport pathways mediating transcellular secretion of urate across the
      proximal tubule were investigated in brush-border membrane vesicles (BBMV)
      isolated from avian kidney. An inside-positive K diffusion potential induced a
      conductive uptake of urate to levels exceeding equilibrium. Protonophore-induced
      dissipation of membrane potential significantly reduced voltage-driven urate
      uptake. Conductive uptake of urate was inhibitor sensitive, substrate specific,
      and a saturable function of urate concentration. Urate uptake was trans
      stimulated by urate and cis-inhibited by p-aminohippurate (PAH). Conductive
      uptake of PAH was cis-inhibited by urate. Urate uptake was unaffected by an
      outward alpha-ketoglutarate gradient. In the absence of a membrane potential,
      urate uptake was similar in the presence and absence of an imposed inside
      alkaline pH gradient or an outward Cl gradient. These observations suggest a
      uniporter-mediated facilitated diffusion of urate as a pathway for passive efflux
      across the brush border membrane of urate-secreting proximal tubule cells.

PMID- 12225980
TI  - Potassium depletion increases potassium clearance capacity in skeletal muscles in
      vivo during acute repletion.
AB  - Muscular K uptake depends on skeletal muscle Na-K-ATPase concentration and
      activity. Reduced K uptake is observed in vitro in K-depleted rats. We evaluated
      skeletal muscle K clearance capacity in vivo in rats K depleted for 14 days.
      [(3)H]ouabain binding, alpha(1) and alpha(2) Na-K-ATPase isoform abundance, and
      K, Na, and Mg content were measured in skeletal muscles. Skeletal muscle K, Na,
      and Mg and plasma K were measured in relation to intravenous KCl infusion that
      continued until animals died, i.e., maximum KCl dose was administered. In soleus,
      extensor digitorum longus (EDL), and gastrocnemius muscles K depletion
      significantly reduced K content by 18%, 15%, and 19%, [(3)H]ouabain binding by
      36%, 41%, and 68%, and alpha(2) isoform abundance by 34%, 44%, and 70%,
      respectively. No significant change was observed in alpha(1) isoform abundance.
      In EDL and gastrocnemius muscles K depletion significantly increased Na (48% and
      59%) and Mg (10% and 17%) content, but only tendencies to increase were observed
      in soleus muscle. K-depleted rats tolerated up to a fourfold higher KCl dose.
      This was associated with a reduced rate of increase in plasma K and increases in
      soleus, EDL, and gastrocnemius muscle K of 56%, 42%, and 41%, respectively, but
      only tendencies to increase in controls. However, whereas K uptake was highest in
      K-depleted animals, the K uptake rate was highest in controls. In vivo K
      depletion is associated with markedly increased K tolerance and K clearance
      despite significantly reduced skeletal muscle Na-K-ATPase concentration. The
      concern of an increased risk for K intoxication during K repletion seems
      unwarranted.

PMID- 12225981
TI  - Amiloride-sensitive sodium current in everted Ambystoma initial collecting
      tubule: short-term insulin effects.
AB  - Whole cell patch-clamp techniques were used to investigate amiloride-sensitive
      sodium conductance (G(Na)) in the everted initial collecting tubule of Ambystoma.
      Accessibility to both the apical and basolateral membranes made this preparation
      ideal for studying the regulation of sodium transport by insulin. G(Na) accounted
      for 20% of total cell conductance (G(T)) under control conditions. A resting
      membrane potential of -75 +/- 2 mV (n = 7) together with the fact that G(T) is
      stable with time suggested that the cells studied were viable. Measurements of
      capacitance and use of a known uncoupling agent, heptanol, suggested that cells
      were not electrically coupled. Thus the values of G(T) and G(Na) represented
      individual principal cells. Exposure of the basolateral membrane to insulin (1
      mU/ml) for 10-60 min significantly (P < 0.05) increased the normalized G(Na) [1.2
      +/- 0.3 nS (n = 6) vs. 2.0 +/- 0.4 nS (n = 6)]. Cell-attached patch-clamp
      techniques were used to further elucidate the mechanism by which insulin
      increases amiloride-sensitive epithelial sodium channel (ENaC) activity. In the
      presence of insulin there was no apparent change in either the number of active
      levels/patch or the conductance of ENaC. The open probability increased
      significantly (P < 0.01) from 0.21 +/- 0.04 (n = 6) to 0.46 +/- 0.07 (n = 6).
      Thus application of insulin enhanced sodium reabsorption by increasing the
      fraction of time the channel spent in the open state.

PMID- 12225982
TI  - Cellular and molecular responses to increased skeletal muscle loading after
      irradiation.
AB  - Irradiation of rat skeletal muscles before increased loading has been shown to
      prevent compensatory hypertrophy for periods of up to 4 wk, possibly by
      preventing satellite cells from proliferating and providing new myonuclei. Recent
      work suggested that stem cell populations exist that might allow irradiated
      muscles to eventually hypertrophy over time. We report that irradiation
      essentially prevented hypertrophy in rat muscles subjected to 3 mo of functional
      overload (OL-Ir). The time course and magnitude of changes in cellular and
      molecular markers of anabolic and myogenic responses were similar in the OL-Ir
      and the contralateral nonirradiated, overloaded (OL) muscles for the first 3-7
      days. These markers then returned to control levels in OL-Ir muscles while
      remaining elevated in OL muscles. The number of myonuclei and amount of DNA were
      increased markedly in OL but not OL-Ir muscles. Thus it appears that stem cells
      were not added to the irradiated muscles in this time period. These data are
      consistent with the theory that the addition of new myonuclei may be required for
      compensatory hypertrophy in the rat.

PMID- 12225983
TI  - Role of alpha(v)beta(3)-integrin in TNF-alpha-induced endothelial cell migration.
AB  - Tumor necrosis factor-alpha (TNF-alpha), one of the major inflammatory cytokines,
      is known to influence endothelial cell migration. In this study, we demonstrate
      that exposure of calf pulmonary artery endothelial cells to TNF-alpha caused an
      increase in the formation of membrane protrusions and cell migration.
      Fluorescence microscopy revealed an increase in alpha(v)beta(3) focal contacts
      but a decrease in alpha(5)beta(1) focal contacts in TNF-alpha-treated cells. In
      addition, both cell-surface and total cellular expression of alpha(v)beta(3)
      integrins increased significantly, whereas the expression of alpha(5)beta(1)
      integrins was unaltered. Only focal contacts containing alpha(v)beta(3)- but not
      alpha(5)beta(1)-integrins were present in membrane protrusions of cells at the
      migration front. In contrast, robust focal contacts containing alpha(5)beta(1)
      integrins were present in cells behind the migration front. A blocking antibody
      to alpha(v)beta(3), but not a blocking antibody to alpha(5)-integrins,
      significantly inhibited TNF-alpha-induced cell migration. These results indicate
      that in response to TNF-alpha, endothelial cells may increase the activation and
      ligation of alpha(v)beta(3) while decreasing the activation and ligation of
      alpha(5)beta(1)-integrins to facilitate cell migration, a process essential for
      vascular wound healing and angiogenesis.

PMID- 12225984
TI  - AE4 is a DIDS-sensitive Cl(-)/HCO(-)(3) exchanger in the basolateral membrane of
      the renal CCD and the SMG duct.
AB  - The renal cortical collecting duct (CCD) plays an important role in systemic acid
      base homeostasis. The beta-intercalated cells secrete most of the HCO(-)(3),
      which is mediated by a luminal, DIDS-insensitive, Cl(-)/HCO(-)(3) exchange. The
      identity of the luminal exchanger is a matter of debate. Anion exchanger isoform
      4 (AE4) cloned from the rabbit kidney was proposed to perform this function
      (Tsuganezawa H et al. J Biol Chem 276: 8180-8189, 2001). By contrast, it was
      proposed (Royaux IE et al. Proc Natl Acad Sci USA 98: 4221-4226, 2001) that
      pendrin accomplishes this function in the mouse CCD. In the present work, we
      cloned, localized, and characterized the function of the rat AE4. Northern blot
      and RT-PCR showed high levels of AE4 mRNA in the CCD. Expression in HEK-293 and
      LLC-PK(1) cells showed that AE4 is targeted to the plasma membrane. Measurement
      of intracellular pH (pH(i)) revealed that AE4 indeed functions as a Cl(-)/HCO(
      )(3) exchanger. However, AE4 activity was inhibited by DIDS. Immunolocalization
      revealed species-specific expression of AE4. In the rat and mouse CCD and the
      mouse SMG duct AE4 was in the basolateral membrane. By contrast, in the rabbit,
      AE4 was in the luminal and lateral membranes. In both, the rat and rabbit CCD AE4
      was in alpha-intercalated cells. Importantly, localization of AE4 was not
      affected by the systemic acid-base status of the rats. Therefore, we conclude
      that expression and possibly function of AE4 is species specific. In the rat and
      mouse AE4 functions as a Cl(-)/HCO(-)(3) exchanger in the basolateral membrane of
      alpha-intercalated cells and may participate in HCO(-)(3) absorption. In the
      rabbit AE4 may contribute to HCO(-)(3) secretion.

PMID- 12225985
TI  - Apparent elastic modulus and hysteresis of skeletal muscle cells throughout
      differentiation.
AB  - The effect of differentiation on the transverse mechanical properties of
      mammalian myocytes was determined by using atomic force microscopy. The apparent
      elastic modulus increased from 11.5 +/- 1.3 kPa for undifferentiated myoblasts to
      45.3 +/- 4.0 kPa after 8 days of differentiation (P < 0.05). The relative
      contribution of viscosity, as determined from the normalized hysteresis area,
      ranged from 0.13 +/- 0.02 to 0.21 +/- 0.03 and did not change throughout
      differentiation. Myosin expression correlated with the apparent elastic modulus,
      but neither myosin nor beta-tubulin were associated with hysteresis. Microtubules
      did not affect mechanical properties because treatment with colchicine did not
      alter the apparent elastic modulus or hysteresis. Treatment with cytochalasin D
      or 2,3-butanedione 2-monoxime led to a significant reduction in the apparent
      elastic modulus but no change in hysteresis. In summary, skeletal muscle cells
      exhibited viscoelastic behavior that changed during differentiation, yielding an
      increase in the transverse elastic modulus. Major contributors to changes in the
      transverse elastic modulus during differentiation were actin and myosin.

PMID- 12225986
TI  - Aging-related satellite cell differentiation defect occurs prematurely after Ski
      induced muscle hypertrophy.
AB  - To investigate the cause of skeletal muscle weakening during aging we examined
      the sequence of cellular changes in murine muscles. Satellite cells isolated from
      single muscle fibers terminally differentiate progressively less well with
      increasing age of donor. This change is detected before decline in satellite cell
      numbers and all histological changes examined here. In MSVski transgenic mice,
      which show type IIb fiber hypertrophy, initial muscle weakness is followed by
      muscle degeneration in the first year of life. This degeneration is accompanied
      by a spectrum of changes typical of normal muscle aging and a more marked decline
      in satellite cell differentiation efficiency. On a myoD-null genetic background,
      in which satellite cell differentiation is defective, the MSVski muscle phenotype
      is aggravated. This suggests that, on a wild-type genetic background, satellite
      cells are capable of repairing MSVski fibers and preserving muscle integrity in
      early life. We propose that decline in myogenic cell differentiation efficiency
      is an early event in aging-related loss of muscle function, both in normal aging
      and in some late-onset muscle degenerative conditions.

PMID- 12225987
TI  - Inhibition of muscle carbonic anhydrase slows the Ca(2+) transient in rat
      skeletal muscle fibers.
AB  - A countertransport of H(+) is coupled to Ca(2+) transport across the sarcoplasmic
      reticulum (SR) membrane. We propose that SR carbonic anhydrase (CA) accelerates
      the CO(2)-HCO reaction so that H(+) ions, which are exchanged for Ca(2+) ions,
      are produced or buffered in the SR at sufficient rates. Inhibition of this SR-CA
      is expected to reduce the rate of H(+) fluxes, which then will retard the
      kinetics of Ca(2+) transport. Fura 2 signals and isometric force were
      simultaneously recorded in fiber bundles of the soleus (SOL) and extensor
      digitorum longus (EDL) from rats in the absence and presence of the lipophilic CA
      inhibitors L-645151, chlorzolamide (CLZ), and ethoxzolamide (ETZ), as well as the
      hydrophilic inhibitor acetazolamide (ACTZ). Fura 2 and force signals were
      analyzed for time to peak (TTP), 50% decay time (t(50)), and their amplitudes. L
      645151, CLZ, and ETZ significantly increased TTP of fura 2 by 10-25 ms in SOL and
      by 5-7 ms in EDL and TTP of force by 6-30 ms in both muscles. L-645151 and ETZ
      significantly prolonged t(50) of fura 2 and force by 20-55 and 40-160 ms,
      respectively, in SOL and EDL. L-645151, CLZ, and ETZ also increased peak force of
      single twitches and amplitudes of fura fluorescence ratio (R(340/380)) at an
      excitation wavelength of 340 to 380 nm. All effects of CA inhibitors on fura 2
      and force signals could be reversed. ACTZ did not affect TTP, t(50), and
      amplitudes of fura 2 signals or force. L-645151, CLZ, and ETZ had no effects on
      myosin-, Ca(2+)-, and Na(+)-K(+)-ATPase activities, nor did they affect the
      amplitude and half-width of action potentials. We conclude that inhibition of SR
      CA by impairing H(+) countertransport is responsible for deceleration of
      intracellular Ca(2+) transients and contraction times.

PMID- 12225988
TI  - Spatial and temporal traction response in human airway smooth muscle cells.
AB  - Tractions that cells exert on their substrates are essential in cell spreading,
      migration, and contraction. These tractions can be determined by plating the
      cells on a flexible gel and measuring the deformation of the gel by using
      fluorescent beads embedded just below the surface of the gel. In this article we
      describe the image correlation method (ICM) optimized for determining the
      displacement field of the gel under a contracting cell. For the calculation of
      the traction field from the displacement field we use the recently developed
      method of Fourier transform traction cytometry (FTTC). The ICM and FTTC methods
      are applied to human airway smooth muscle cells during stimulation with the
      contractile agonist histamine or the relaxing agonist isoproterenol. The overall
      intensity of the cell contraction (the median traction magnitude, the energy
      transferred from the cell to the gel, and the net contractile moment) increased
      after activation with histamine, and decreased after treatment with
      isoproterenol. Cells exhibited regional differences in the time course of
      traction during the treatment. Both temporal evolution and magnitude of traction
      increase induced by histamine varied markedly among different cell protrusions,
      whereas the nuclear region showed the smallest response. These results suggest
      that intracellular mediators of cell adhesion and contraction respond to
      contractile stimuli with different rates and intensities in different regions of
      the cell.

PMID- 12225989
TI  - Induction of cyclooxygenase-2 by heat shock protein 60 in macrophages and
      endothelial cells.
AB  - The 60-kDa heat shock protein (HSP60), an endogenous ligand for the toll-like 4
      receptor, is generated in response to inflammation, tissue injury, and/or stress
      and stimulates macrophages to produce cytotoxic and proinflammatory mediators
      including nitric oxide, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6,
      and IL-12. In the present studies we report that HSP60 is an effective inducer of
      cyclooxygenase-2 (COX-2) in macrophages, as well as endothelial cells. In both
      cell types, the synthesis of COX-2 was coordinate with induction of nitric oxide
      synthase (NOS)-2 and with nitric oxide production. With the use of promoter
      constructs in transient transfection assays, optimal expression of COX-2 in
      macrophages was found to require nuclear factor (NF)-kappaB, the cAMP-response
      element (CRE), and NF-IL-6, but not the E-box. Mobility shift assays revealed
      that HSP60 induced NF-kappaB and CRE binding activity, while CCAAT/enhancer
      binding protein (C/EBP), which binds to NF-IL-6, was constitutively active in the
      cells. Both c-Jun and CRE binding protein (CREB) bound to the CRE, while C/EBP
      beta bound to NF-IL-6. These data indicate that NF-kappaB, C/EBP-beta, c-Jun, and
      CREB are important in HSP60-induced expression of COX-2. The c-Jun-NH(2)-terminal
      kinase (JNK), p44/42 mitogen-activated protein (MAP) kinase [extracellular signal
      regulated kinase 1/2 (ERK1/2)], and p38 MAP kinase were rapidly activated by
      HSP60 in the macrophages. PD-98059, an inhibitor of phosphorylation of ERK1/2,
      caused a marked inhibition of HSP60-induced COX-2 and NOS-2 expression.
      Unexpectedly, SB-203580, a p38 kinase antagonist, was found to block HSP60
      induced expression of COX-2, but not NOS-2. These data indicate that both ERK1/2
      kinase and p38 kinase play a role in regulating HSP60-induced expression of COX
      2.

PMID- 12225990
TI  - Differentiation in C(2)C(12) myoblasts depends on the expression of endogenous
      IGFs and not serum depletion.
AB  - Myogenic differentiation in vitro has been usually viewed as being negatively
      controlled by serum mitogens. A depletion of critical serum components from
      medium has been considered to be essential for permanent withdrawal from the cell
      cycle and terminal differentiation of myoblasts. Removal of serum mitogens
      induces the expression of insulin-like growth factors (IGFs), whereas it inhibits
      that of basic fibroblast growth factor (bFGF) and transforming growth factor
      (TGF)-beta in myoblasts. These responses of growth factors to medium conditioning
      seem to be well matched to their functions in proliferation/differentiation. In
      the present study, we showed that C(2)C(12) myoblasts differentiated actively,
      even in mitogen-rich medium, and that this medium offered an advantage over
      mitogen-poor medium in terms of increasing differentiation. Our attention focused
      on endogenous growth factors, as described above, especially IGFs in mitogen-rich
      medium. During differentiation, IGF-I and IGF-II mRNA levels increased, but bFGF
      and TGF-beta(1) mRNAs decreased. Differentiation was commensurable with IGF mRNA
      levels and suppressed by antisense oligodeoxynucleotides and neutralizing
      monoclonal antibodies against IGFs. These results suggest that an
      autocrine/paracrine loop of IGFs, bFGF, and TGF-beta(1) is active in
      proliferating and differentiating C(2)C(12) cells without a depletion of serum
      and that endogenous IGFs actively override the negative control of
      differentiation by serum mitogens.

PMID- 12225991
TI  - Phosphorous metabolites and steady-state energetics of transformed fibroblasts
      during three-dimensional growth.
AB  - Rat1-T1 and MR1 spheroids represent separate transformed phenotypes originated
      from the same rat fibroblasts that differ in three-dimensional (3D) growth
      kinetics, histological structure, and oxygenation status. In the present study,
      (31)P-NMR spectroscopy of perfused spheroid suspensions was used to investigate
      cellular energetics relative to 3D growth, development of necrosis, and cell
      cycle distribution. Both spheroid types were characterized by a remarkably low
      amount of free (inorganic) phosphate (P(i)) and a low phosphocreatine peak. The
      ratio of nucleoside triphosphate (NTP) to P(i) ranged between 1.5 and 2.0.
      Intracellular pH, NTP-to-P(i) ratio, and NTP/cell remained constant throughout
      spheroid growth, being unaffected by the emergence of oxygen deficiency, cell
      quiescence, and necrosis. However, a 50% decrease in the ratio of the lipid
      precursors phosphorylcholine and phosphorylethanolamine (PC/PE) was observed with
      increasing spheroid size and was correlated with an increased G(1)/G(0) phase
      cell fraction. In addition, the ratio of the phospholipid degradation products
      glycerophosphorylcholine and glycerophosphorylethanolamine (GPC/GPE) increased
      with spheroid diameter in Rat1-T1 aggregates. We conclude that changes in
      phospholipid metabolism, rather than alterations in energy-rich phosphates,
      reflect cell quiescence in spheroid cultures, because cells in the inner oxygen
      deficient zones seem to adapt their energy metabolism to the environmental
      conditions before necrotic cell destruction.

PMID- 12225992
TI  - Cytochrome c activates K+ channels before inducing apoptosis.
AB  - Cell shrinkage is an early prerequisite for apoptosis. The apoptotic volume
      decrease is due primarily to loss of cytoplasmic ions. Increased outward K+
      currents have indeed been implicated in the early stage of apoptosis in many cell
      types. We found that cytoplasmic dialysis of cytochrome c (cyt-c), a mitochondria
      dependent apoptotic inducer, increases K+ currents before inducing nuclear
      condensation and breakage in pulmonary vascular smooth muscle cells. The cyt-c
      mediated increase in K+ currents took place rapidly and was not affected by
      treatment with a specific inhibitor of caspase-9. Cytoplasmic dialysis of
      recombinant (active) caspase-9 negligibly affected the K+ currents. Furthermore,
      treatment of the cells with staurosporine (ST), an apoptosis inducer that
      mediates translocation of cyt-c from mitochondria to the cytosol, also increased
      K+ currents, caused cell shrinkage, and induced apoptosis (determined by
      apoptotic nuclear morphology and TdT-UTP nick end labeling assay). The
      staurosporine-induced increase in K+ currents concurred to the volume decrease
      but preceded the activation of apoptosis (nuclear condensation and breakage).
      These results suggest that the cyt-c-induced activation of K+ channels and the
      resultant K+ loss play an important role in initiating the apoptotic volume
      decrease when cells undergo apoptosis.

PMID- 12225993
TI  - Lack of both oxygen and glucose contributes to I/R-induced changes in cardiac SR
      function.
AB  - Although ischemia-reperfusion (I/R) has been shown to depress cardiac performance
      and sarcoplasmic reticulum (SR) function, the mechanisms underlying these
      alterations are poorly understood. Because lack of oxygen and substrate
      deprivation are known to occur during the ischemic phase, we examined the effects
      of reperfusion on cardiac performance and SR function in hearts subjected to
      hypoxia and substrate lack. For this purpose, isolated rat hearts were perfused
      with hypoxic and/or glucose-free medium for 30 min and then reperfused with
      normal medium for 1 h; the SR vesicles were isolated for studying the Ca(2+)
      transport activities. Reperfusion with normal medium of hearts deprived of oxygen
      or glucose showed no changes in cardiac performance and SR function. However,
      reperfusion of hearts perfused with hypoxic glucose-free medium showed ~45%
      decrease in cardiac contractile activities as well as 23 and 64% reduction in SR
      Ca(2+)-uptake and Ca(2+)-release activities, respectively, without any change in
      the level of SR Ca(2+)-cycling proteins. Depressed SR function in these hearts
      was associated with a reduction in Ca(2+)/calmodulin-dependent protein kinase
      (CaMK) phosphorylation of the SR Ca(2+)-cycling proteins and 34% decrease in SR
      CaMK activity. These changes in cardiac performance, SR function, and SR CaMK
      activity in the hypoxic, glucose-deprived, reperfused hearts were similar to
      those observed in hearts subjected to 30 min of global ischemia and 60 min of
      reperfusion. The results therefore suggest that the lack of both oxygen and
      substrate during the ischemic phase may contribute to the I/R-induced alterations
      in cardiac performance and SR function. Furthermore, these abnormalities were
      associated with reduced SR CaMK activity.

PMID- 12225994
TI  - Cell cycle-dependent expression of volume-activated chloride currents in
      nasopharyngeal carcinoma cells.
AB  - Patch-clamping and cell image analysis techniques were used to study the
      expression of the volume-activated Cl(-) current, I(Cl(vol)), and regulatory
      volume decrease (RVD) capacity in the cell cycle in nasopharyngeal carcinoma
      cells (CNE-2Z). Hypotonic challenge caused CNE-2Z cells to swell and activated a
      Cl(-) current with a linear conductance, negligible time-dependent inactivation,
      and a reversal potential close to the Cl(-) equilibrium potential. The sequence
      of anion permeability was I(-) > Br(-) > Cl(-) > gluconate. The Cl(-) channel
      blockers tamoxifen, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), and ATP
      inhibited I(Cl(vol)). Synchronous cultures of cells were obtained by the mitotic
      shake-off technique and by a double chemical-block (thymidine and hydroxyurea)
      technique. The expression of I(Cl(vol)) was cell cycle dependent, being high in
      G(1) phase, downregulated in S phase, but increasing again in M phase. Hypotonic
      solution activated RVD, which was cell cycle dependent and inhibited by the Cl(-)
      channel blockers NPPB, tamoxifen, and ATP. The expression of I(Cl(vol)) was
      closely correlated with the RVD capacity in the cell cycle, suggesting a
      functional relationship. Inhibition of I(Cl(vol)) by NPPB (100 microM) arrested
      cells in G(0)/G(1). The data also suggest that expression of I(Cl(vol)) and RVD
      capacity are actively modulated during the cell cycle. The volume-activated Cl(-)
      current associated with RVD may therefore play an important role during the cell
      cycle progress.

PMID- 12225995
TI  - Expression of glucocorticoid receptor alpha- and beta-isoforms in human cells and
      tissues.
AB  - Alternative splicing of the human glucocorticoid receptor (GR) primary transcript
      generates two protein isoforms: GR-alpha and GR-beta. We investigated the
      expression of both GR isoforms in healthy human cells and tissues. GR-alpha mRNA
      abundance (x10(6) cDNA copies/microg total RNA) was as follows: brain (3.83 +/-
      0.80) > skeletal muscle > macrophages > lung > kidney > liver > heart >
      eosinophils > peripheral blood mononuclear cells (PBMCs) > nasal mucosa >
      neutrophils > colon (0.33 +/- 0.04). GR-beta mRNA was much less expressed than GR
      alpha mRNA. Its abundance (x10(3) cDNA copies/microg total RNA) was as follows:
      eosinophils (1.55 +/- 0.58) > PBMCs > liver > or = skeletal muscle > kidney >
      macrophages > lung > neutrophils > brain > or = nasal mucosa > heart (0.15 +/-
      0.08). GR-beta mRNA was not found in colon. While GR-alpha protein was detected
      in all cells and tissues, GR-beta was not detected in any specimen. Our results
      suggest that, in physiological conditions, the default splicing pathway is the
      one leading to GR-alpha. The alternative splicing event leading to GR-beta is
      minimally activated.

PMID- 12225996
TI  - Analysis of perinatal mortality and its components: time for a change?
AB  - Since the midtwentieth century, stillbirths (late fetal deaths) and early
      neonatal deaths have often been combined into a single category of "perinatal"
      deaths. In the past, such a combination was justified by the fact that asphyxia
      was a common cause of death during labor (intrapartum stillbirth) and shortly
      after birth and by geographic and temporal differences in classification of
      livebirths versus stillbirths. In more recent years, however, the etiologic
      determinants have diverged sharply, with many fewer early neonatal deaths caused
      by asphyxia and relatively many more caused by congenital anomalies. Moreover,
      the increasingly common stratification of pregnancy outcome measures by
      gestational age or birth weight leads to the use of an inappropriate denominator
      (total livebirths plus stillbirths within each gestational age or birth weight
      category) for denoting risk for the stillbirth component, because all unborn
      fetuses (including the majority of those not born within the specified
      gestational age or birth weight range) are at risk of being stillborn in that
      range. The authors suggest that, whenever possible, stillbirths and early
      neonatal deaths should be reported separately, with gestational age-specific
      risks of stillbirth based on all fetuses at risk, and that antepartum and
      intrapartum stillbirths be reported separately.

PMID- 12225997
TI  - Influence of maternal glucose level on ethnic differences in birth weight and
      pregnancy outcome.
AB  - Minority ethnicity increases the risk of a poor pregnancy outcome in the United
      States. The mechanism(s) whereby this occurs is unknown. One possibility is
      physiologic variation in levels of maternal glucose, the major substrate for
      fetal growth, which is metabolized from the maternal diet and endogenous
      gluconeogenic sources. The authors examined whether postload glucose
      concentration at week 28 was associated with maternal ethnicity or altered the
      ethnic difference in birth weight after adjustment for duration of gestation (to
      index fetal growth) and pregnancy outcome (large- and small-for-gestational-age
      births) among 2,072 diabetes-free gravidas in Camden, New Jersey (1990-2001).
      After data were controlled for potentially confounding factors, maternal glucose
      level was significantly lower for African Americans than for Hispanics (mainly
      Puerto Ricans) or Whites. Maternal glucose was associated with infant birth
      weight to a similar extent within each ethnic group (1.5-2.0 g of birth weight
      per mg/dl of maternal glucose). A comparison of regression coefficients from
      models with and without glucose indicated small but statistically significant
      effects of glucose on the ethnic difference in birth weight and the risk of large
      for-gestational-age birth between African Americans and Whites. Maternal glucose
      concentration did not differ between Hispanics and Whites; consequently, glucose
      did not influence this ethnic difference in birth weight and pregnancy outcome.

PMID- 12225998
TI  - Risk of breast cancer classified by joint estrogen receptor and progesterone
      receptor status among women 20-44 years of age.
AB  - To gain insight into whether breast cancer tumors jointly classified by estrogen
      receptor (ER) and progesterone receptor (PR) status represent diseases with
      differing etiologies, data from a population-based case-control study of US women
      20-44 years of age were analyzed. Cases included 1,556 women diagnosed between
      1990 and 1992. Age- and geographic-frequency-matched controls included 1,397
      women identified by random digit dialing. Heterogeneity between ER+PR+ and ER-PR-
      tumors was most pronounced in relation to age, race, and recreational exercise at
      12-13 years of age. Multivariate-adjusted odds ratios for ER+PR+ tumors were 0.64
      (95% confidence interval (CI): 0.47, 0.89) for 30-34 versus 40-44 years of age,
      0.89 (95% CI: 0.63, 1.25) for Black versus White race, and 0.84 (95% CI: 0.68,
      1.03) for exercise at 12-13 years of age above versus at or below the median.
      Corresponding odds ratios for ER-PR- tumors were 1.24 (95% CI: 0.86, 1.77), 1.51
      (95% CI: 1.07, 2.14), and 1.15 (95% CI: 0.90, 1.48). Risk of ER-PR- cancer in
      relation to menstrual and reproductive (parity and lactation) characteristics,
      alcohol consumption, and family history of breast cancer was similar to that
      observed for ER+PR+ tumors. These findings only modestly support the hypothesis
      that hormonally related risk factors have differing relations with ER+PR+ versus
      ER-PR- tumors among younger women.

PMID- 12225999
TI  - Family history of cancer and incidence of acute leukemia in adults.
AB  - Family history of cancer may represent shared genetic and environmental risk
      factors for leukemia. The authors examined associations of first-degree family
      history of cancer with adult acute leukemia incidence by using data on 811
      patients (or their proxies) identified at diagnosis and 637 population-based
      controls in the United States and Canada during 1986-1990. For proxy-interviewed
      patients, relative risks were elevated for family history of any cancer (relative
      risk = 1.7, 95% confidence interval (CI): 1.3, 2.4), hematopoietic cancer
      (relative risk = 1.8, 95% CI: 1.1, 3.0), leukemia (relative risk = 2.4, 95% CI:
      1.3, 4.6), and breast cancer (relative risk = 1.7, 95% CI: 1.0, 3.0) but not for
      colorectal, prostate, or lung cancer. For self-interviewed patients, family
      history of hematopoietic cancer was inversely associated with leukemia incidence
      (relative risk = 0.6, 95% CI: 0.4, 1.1). Regardless of patient interview type,
      history of breast cancer in sisters was positively associated with adult acute
      leukemia, whereas history of breast cancer in mothers was not. The role of family
      history of cancer in leukemia etiology is unclear because of differential
      reporting by patients and proxies. Specifically, self-interviewed patients may
      underreport cancer in their first-degree relatives. Associations between family
      history of breast cancer and leukemia incidence may be the result of unmeasured,
      shared etiologies specific to these cancers.

PMID- 12226000
TI  - Anthropometric characteristics, physical activity, and risk of non-Hodgkin's
      lymphoma subtypes and B-cell chronic lymphocytic leukemia: a prospective study.
AB  - Anthropometric characteristics, physical activity, and risk of non-Hodgkin's
      lymphoma, its subtypes, and B-cell chronic lymphocytic leukemia (B-CLL) were
      evaluated in a prospective cohort study of 37,931 Iowa women who were aged 55-69
      years at baseline in 1986. Through 1998, 261 cases of non-Hodgkin's lymphoma (137
      diffuse, 58 follicular, and 32 small lymphocytic lymphomas) and 63 cases of B-CLL
      were identified by linkage to the Iowa Cancer Registry. Height, weight, body mass
      index, waist/hip ratio, and physical activity were not associated with risk of
      non-Hodgkin's lymphoma overall or with diffuse or follicular lymphoma in
      particular. After adjustment for other non-Hodgkin's lymphoma risk factors, there
      was an inverse association of baseline body mass index (relative risks (RRs)
      across quartiles: 1, 0.4, 0.4, 0.3; p trend = 0.03) with risk of small
      lymphocytic lymphoma. In contrast, for B-CLL there were suggestive positive
      associations with body mass index at age 50 years (RRs across quartiles: 1, 1.9,
      1.5, 2.7; p trend = 0.03) and (more weakly) baseline body mass index (RRs across
      quartiles: 1, 1.1, 1.6, 1.3; p trend = 0.3). In summary, we found no evidence
      that height, weight, body mass, or physical activity plays an important role in
      non-Hodgkin's lymphoma overall or in diffuse or follicular lymphoma in
      particular. The opposite associations of body mass index with small lymphocytic
      lymphoma versus B-CLL may be a chance finding but, if confirmed, would suggest
      different etiologies for these malignancies.

PMID- 12226001
TI  - Dietary carotenoids, serum beta-carotene, and retinol and risk of lung cancer in
      the alpha-tocopherol, beta-carotene cohort study.
AB  - Findings from several beta-carotene supplementation trials were unexpected and
      conflicted with most observational studies. Carotenoids other than beta-carotene
      are found in a variety of fruits and vegetables and may play a role in this
      important malignancy, but previous findings regarding the five major carotenoids
      are inconsistent. The authors analyzed the associations between dietary beta
      carotene, beta-carotene, lutein/zeaxanthin, lycopene, beta-cryptoxanthin, vitamin
      A, serum beta-carotene, and serum retinol and the lung cancer risk in the Alpha
      Tocopherol, Beta-Carotene Cancer Prevention Study cohort of male smokers
      conducted in southwestern Finland between 1985 and 1993. Of the 27,084 male
      smokers aged 50-69 years who completed the 276-food item dietary questionnaire at
      baseline, 1,644 developed lung cancer during up to 14 years of follow-up. Cox
      proportional hazards models were used to estimate relative risks and 95%
      confidence intervals. Consumption of fruits and vegetables was associated with a
      lower lung cancer risk (relative risk = 0.73, 95% confidence interval: 0.62,
      0.86, highest vs. lowest quintile). Lower risks of lung cancer were observed for
      the highest versus the lowest quintiles of lycopene (28%), lutein/zeaxanthin
      (17%), beta-cryptoxanthin (15%), total carotenoids (16%), serum beta-carotene
      (19%), and serum retinol (27%). These findings suggest that high fruit and
      vegetable consumption, particularly a diet rich in carotenoids, tomatoes, and
      tomato-based products, may reduce the risk of lung cancer.

PMID- 12226002
TI  - Exposure to residential radon and lung cancer in Spain: a population-based case
      control study.
AB  - Although high radon concentrations have been linked to increased risk of lung
      cancer by both experimental studies and investigations of underground miners,
      epidemiologic studies of residential radon exposure display inconsistencies. The
      authors therefore decided to conduct a population-based case-control study in
      northwest Spain to determine the risk of lung cancer associated with exposure to
      residential radon. The study covered a total of 163 subjects with incident lung
      cancer and a population sample of 241 cancer-free subjects since 1992-1994. Odds
      ratios for radon were estimated using logistic regression adjusted for sex, age,
      lifetime tobacco use, family history, and habitat. The adjusted odds ratios for
      the second, third, and fourth quartiles of radon (breakpoints: 37.0, 55.2, and
      148.0 Bq/m(3)) were 2.73 (95% confidence interval (CI): 1.12, 5.48), 2.48 (95%
      CI: 1.29, 6.79), and 2.96 (95% CI: 1.29, 6.79), respectively. An additive
      synergic effect between radon and tobacco was found. The results from this study
      suggest that, even at concentrations far below official guideline levels, radon
      may lead to a 2.5-fold rise in the risk of lung cancer. Furthermore, the synergy
      found between smoking and radon may prove useful when it comes to drafting public
      health recommendations.

PMID- 12226003
TI  - Mortality from cancer and other causes among airline cabin attendants in Germany,
      1960-1997.
AB  - Airline cabin attendants are exposed to several potential occupational hazards,
      including cosmic radiation. Little is known about the mortality pattern and
      cancer risk of these persons. The authors conducted a historical cohort study
      among cabin attendants who had been employed by two German airlines in 1953 or
      later. Mortality follow-up was completed through December 31, 1997. The authors
      computed standardized mortality ratios (SMRs) for specific causes of death using
      German population rates. The effect of duration of employment was evaluated with
      Poisson regression. The cohort included 16,014 women and 4,537 men (approximately
      250,000 person-years of follow-up). Among women, the total number of deaths (n =
      141) was lower than expected (SMR = 0.79, 95% confidence interval (CI): 0.67,
      0.94). The SMR for all cancers (n = 44) was 0.79 (95% CI: 0.54, 1.17), and the
      SMR for breast cancer (n = 19) was 1.28 (95% CI: 0.72, 2.20). The SMR did not
      increase with duration of employment. Among men, 170 deaths were observed (SMR =
      1.10, 95% CI: 0.94, 1.28). The SMR for all cancers (n = 21) was 0.71 (95% CI:
      0.41, 1.18). The authors found a high number of deaths from acquired
      immunodeficiency syndrome (SMR = 40; 95% CI: 28.9, 55.8) and from aircraft
      accidents among the men. In this cohort, ionizing radiation probably contributed
      less to the small excess in breast cancer mortality than reproductive risk
      factors. Occupational causes seem not to contribute strongly to the mortality of
      airline cabin attendants.

PMID- 12226004
TI  - Advanced detection of time trends in long-term cancer patient survival:
      experience from 50 years of cancer registration in Finland.
AB  - Timely monitoring of trends in long-term patient survival is an important task of
      cancer registries. Recently, a new method, denoted period analysis, has been
      proposed to enhance up-to-date monitoring of survival. The authors assessed the
      use of period analysis for advanced detection of time trends in long-term cancer
      patient survival based on data from the nationwide Finnish Cancer Registry by
      comparing estimates of 10-, 15-, and 20-year relative survival rates obtained by
      period analysis and by traditional (cohort) analysis of survival at various
      points of time between 1953 and 1997. Time trends are graphically displayed for
      the 15 most common forms of cancer. Long-term survival rates strongly improved
      over time for most forms of cancer. The slope and shape of trend curves obtained
      by period analysis are very similar to those obtained by traditional survival
      analysis. However, detection of progress in 10-, 15-, and 20-year survival rates
      of newly diagnosed patients could have been advanced by 5-10 years, 10-15 years,
      and 15-20 years, respectively, with the use of period analysis rather than
      traditional cohort survival analysis. The authors conclude that period analysis
      should be routinely used to advance detection of progress in long-term cancer
      patient survival.

PMID- 12226005
TI  - Factor analysis of Gulf War illness: what does it add to our understanding of
      possible health effects of deployment?
AB  - The authors conducted factor analysis on survey data from 1,779 Persian Gulf War
      veterans. Their purposes were to: 1) determine whether factor analysis identified
      a unique "Gulf War syndrome" among veterans potentially exposed to chemical
      warfare agents; 2) compare the findings of factor analysis with those from an
      epidemiologic analysis of symptom prevalence; and 3) observe the behavior of
      factor analysis when performed on dichotomous data. The factor analysis
      identified three factors, but they were not unique to any particular deployment
      group. A unique pattern of illness was not found for the larger group of veterans
      potentially exposed to chemical warfare agents; however, veterans who had
      witnessed the demolition of chemical warfare agents at the Khamisiyah site in
      Iraq had a greater prevalence of dysesthesia. An analysis of the performance of
      dichotomous variables in factor analysis showed that the standard criteria used
      to determine the number of relevant factors and the dominant variables within
      them may be inappropriate. While Gulf War veterans appear to suffer an increased
      burden of illness, there is insufficient evidence to identify a unique syndrome
      in this population of deployed servicemen and women. Furthermore, the results
      provide evidence that factor analysis may make a limited contribution in this
      area of research.

PMID- 12226006
TI  - From anti-inflammatory drugs through antifibrotic agents to lung transplantation:
      a long road of research, clinical attempts, and failures in the treatment of
      idiopathic pulmonary fibrosis.

PMID- 12226007
TI  - Neutrophils or eosinophils in young children with wheezing: which comes first?

PMID- 12226008
TI  - Beta(2)-agonists: deja vu all over again: the second-generation controversy.

PMID- 12226009
TI  - Cephalometric measurements and sleep apnea hypopnea syndrome.

PMID- 12226010
TI  - The changing landscape of HIV-related lung disease in the era of highly active
      antiretroviral therapy.

PMID- 12226011
TI  - What is the best way to measure cardiac output? Who cares, anyway?

PMID- 12226012
TI  - A waist is a terrible thing to mind: central obesity, the metabolic syndrome, and
      sleep apnea hypopnea syndrome.

PMID- 12226013
TI  - Predicting survival of lung transplantation candidates with idiopathic
      interstitial pneumonia: does PaO(2) predict survival?
AB  - OBJECTIVE: To find a parameter that would discriminate between the patients with
      idiopathic interstitial pneumonia who survived to undergo transplantation and
      those who died while waiting to undergo transplantation. METHODS: A retrospective
      review was performed of all lung transplant referrals for idiopathic interstitial
      pneumonia that were listed with United Network for Organ Sharing at the
      University of California San Diego from January 1990 to February 1999. Of the 331
      patients who were listed, 48 met the eligibility criteria. Patient demographics,
      radiographic studies, pathology reports, and the results of resting and exercise
      cardiopulmonary function tests were recorded from each patient's chart. Patients
      were divided into the following two groups: those patients who survived until
      transplantation and those still waiting were classified as "alive"; and those
      patients who died before undergoing transplantation were classified as
      "deceased." RESULTS: Forty-three of 48 patients had a pathologic diagnosis. The
      cohort included 25 patients with usual interstitial pneumonitis, 3 patients with
      nonspecific interstitial pneumonitis, 1 patient with desquamative interstitial
      pneumonitis, and 14 patients with interstitial lung disease of unknown etiology.
      The only significant difference between the two groups was resting PaO(2) (p =
      0.035). A stepwise multivariate analysis demonstrated that PaO(2) and FEV(1)/FVC
      ratio were significantly associated with survival (hazards ratio, 1.06;
      confidence interval, 0.99 to 1.13; p = 0.019). CONCLUSIONS: A survival analysis
      using PaO(2) and FEV(1)/FVC ratio values proved to be statistically significant,
      but a prospective trial is needed to determine the clinical relevance of these
      parameters for predicting survival in patients with idiopathic interstitial
      pneumonia.

PMID- 12226014
TI  - Fludarabine-related pulmonary toxicity: a distinct clinical entity in chronic
      lymphoproliferative syndromes.
AB  - BACKGROUND: Little is known about lung injury caused by fludarabine therapy.
      OBJECTIVES: To establish a case definition, to describe management, and to
      identify risk factors for fludarabine-related pulmonary toxicity. DESIGN: Case
      control study. SETTING: Tertiary-care US Army teaching hospital. PATIENTS:
      Individuals treated with fludarabine at our institution between January 1989 and
      June 2000. MEASUREMENTS: Cases of fludarabine-related pulmonary toxicity were
      defined as follows: dyspnea, fever, hypoxemia, and radiographic infiltrates seen
      in a patient treated with fludarabine; cases were excluded if there was evidence
      of pulmonary infection or progression of underlying lymphoproliferative disease
      affecting the lungs. For each case, demographic data, medical history,
      radiographic information, available bronchoscopy and pathology data, and details
      of treatment were reviewed. Cases were compared with fludarabine-treated control
      subjects to identify potential risk factors. Comparisons were made with regard to
      age, gender, history of underlying lung disease, lymphoproliferative diagnosis,
      prior chemotherapy, fludarabine treatment regimen, and pretreatment chest
      radiograph. RESULTS: During the study period, 105 patients were treated with
      fludarabine. The incidence of fludarabine-related pulmonary toxicity using our
      definition was 8.6% (95% confidence interval [CI], 3.2 to 13.9%). One patient
      died before this entity was suspected; the remainder of the patients underwent
      bronchoscopy to exclude infection. Patients were treated with corticosteroids
      with subjective and objective benefits. One patient later died of apparent
      infection during steroid therapy. One patient was retreated with fludarabine and
      symptoms of lung toxicity developed again. Patients (n = 9) were similar to
      control subjects (n = 96) with respect to age, gender, history of underlying lung
      disease, previous chemotherapy, and fludarabine regimen. Patients with chronic
      lymphocytic leukemia were 13.3 (95% CI, 1.6 to 300.6) times more likely to have
      toxicity develop than patients treated with fludarabine for other diagnoses.
      There was a trend toward an increased incidence in patients with interstitial
      infiltrates apparent on prefludarabine chest radiographs. CONCLUSIONS: A variety
      of lung conditions arise in patients treated with fludarabine; however, this
      agent seems to cause direct pulmonary toxicity. After performing an appropriate
      evaluation to exclude infection, corticosteroids are an effective therapy. The
      relative frequency of this condition and potential for mortality underscore the
      need for increased clinician awareness of fludarabine-related pulmonary toxicity
      and its risk factors.

PMID- 12226015
TI  - Bronchoalveolar cells in children < 3 years old with severe recurrent wheezing.
AB  - STUDY OBJECTIVE: To determine the cell profile of BAL from infants with severe
      recurrent wheezing who were not acutely ill at the time of investigation,
      suggesting an ongoing inflammation. DESIGN AND PATIENTS: In a retrospective
      study, we determined BAL cell profiles for 83 children with wheezing aged 4 to 32
      months (mean +/- SD, 11.3 +/- 5.5 months). Fiberoptic bronchoscopy was performed
      in children with severe recurrent wheezy bronchitis unresponsive to inhaled
      steroids. These children were compared with 17 children aged 6 to 36 months
      (mean, 15.1 +/- 7.5 months) with various nonwheezing pulmonary diseases. Children
      were included as control subjects if they had no endobronchial inflammation and
      no atopy. RESULTS: The BAL cell profile of young children with wheezing typically
      includes a significantly higher cell count (mean, 644.4 +/- 956.8 x 10(3)/mL vs
      313 +/- 203.2 x 10(3)/mL, p = 0.008), a significantly higher percentage of
      neutrophils (mean, 9 +/- 12.1% vs 2.1 +/- 2.2%, p = 0.003), and a higher
      neutrophil count (mean, 43.2 +/- 81.6 x 10(3)/mL vs 7.9 +/- 11.8 x 10(3)/mL, p =
      0.003), as compared with control subjects. The larger number of neutrophils in
      children with wheezing was not correlated with bacterial or viral infection, or
      with age, sex, or atopic status. In contrast to the situation in asthmatic
      adults, eosinophil levels were not higher in children with wheezing than in
      control subjects (mean, 0.09 +/- 0.27% vs 0.08 +/- 0.25%). CONCLUSION: Neutrophil
      mediated inflammation in the airways appears to better characterize severe
      recurrent wheezing in children < 3 years old.

PMID- 12226016
TI  - Effect of salmeterol on seasonal changes in airway responsiveness and exhaled
      nitric oxide in pollen-sensitive asthmatic subjects.
AB  - OBJECTIVE: Using a model of natural allergen exposure, we examined the effect of
      regular treatment with salmeterol on allergen-induced changes in airway
      responsiveness and exhaled nitric oxide (ENO). DESIGN: Double-blind, randomized,
      parallel-group study. SETTING: Specialist allergy unit in a university hospital.
      PATIENTS: Asthmatic patients sensitized to pollen allergens were randomly
      allocated to monotherapy with salmeterol (n = 14) or placebo (n = 13).
      INTERVENTIONS: Salmeterol, 25 micro g, and placebo inhalers, two puffs bid, for 6
      weeks. MEASUREMENTS: Spirometry, the level of a provocative concentration of a
      substance (methacholine) causing a 20% fall in FEV(1) (PC(20)), the PC(20) level
      for adenosine 5'-monophosphate (AMP), and ENO were measured before the pollen
      season and were repeated at the height of the pollen season after 6 weeks of
      treatment with salmeterol or placebo. RESULTS: The decrease in FEV(1) during the
      pollen season was significantly larger in the placebo group than in the
      salmeterol group, the mean difference in the change between the groups being 0.20
      L (95% confidence interval, 0.03 to 0.35; p = 0.047). Changes in PC(20) for
      methacholine, PC(20) for AMP, and ENO levels were not significantly different
      between treatment groups. However, a mean (+/- SEM) decrease in the PC(20) for
      methacholine of -1.0 +/- 0.4 doubling concentrations was observed within the
      placebo group (p = 0.03), whereas no significant changes were observed within the
      salmeterol group. A significant decrease in PC(20) for AMP (doubling
      concentrations) was observed within the placebo group (-2.1 +/- 0.6; p = 0.003)
      and the salmeterol group (-1.5 +/- 0.4; p = 0.003). ENO concentrations increased
      significantly among the placebo and the salmeterol groups during natural pollen
      exposure. CONCLUSION: These observations indicate that natural allergen exposure
      and the regular use of salmeterol are not associated with a greater increase in
      ENO and airway responsiveness than allergen exposure alone.

PMID- 12226017
TI  - Fluticasone propionate via the Diskhaler or hydrofluoroalkane-134a metered-dose
      inhaler on methacholine-induced airway hyperresponsiveness.
AB  - STUDY OBJECTIVE: s: To compare the effect of 4 weeks of treatment with
      fluticasone propionate (FP), 100 micro g bid, delivered either via the Diskhaler
      (GlaxoSmithKline; Middlesex, UK) or a hydrofluoroalkane (HFA)-134a pressurized
      metered-dose inhaler (pMDI) on airway responsiveness. DESIGN: A single-center,
      randomized, double-blind, double-dummy, placebo-controlled crossover study.
      SETTING: Outpatients. PATIENTS: Patients with mild asthma who had not received
      corticosteroids for 4 weeks prior to the study. INTERVENTIONS: FP, 100 micro g
      bid, via the Diskhaler, HFA-134a pMDI, or placebo for periods of 4 weeks.
      MEASUREMENTS AND RESULTS: The primary efficacy variable was the provocative dose
      of methacholine causing a 20% fall in FEV(1) (PD(20)) at the end of each 4-week
      treatment period. The FP formulations were defined as equivalent if the treatment
      difference was within +/- 1 doubling dose of methacholine. Forty-seven patients
      were included in the per-protocol population. The baseline PD(20) geometric mean
      was 0.21 mg, which increased to 0.55 mg with FP via the HFA-134a pMDI and to 0.68
      mg with FP via the Diskhaler. The treatment difference between adjusted means was
      - 0.16 doubling doses (95% confidence interval, - 0.62 to 0.31 doubling doses; p
      = 0.503). Both significantly decreased airway responsiveness compared to placebo
      (p < 0.001), and also significantly increased lung function with no difference
      between the two active groups. FP was well tolerated with few adverse events and
      no effect on serum cortisol levels. CONCLUSIONS: FP delivered via the HFA-134a
      pMDI is equivalent to FP via the Diskhaler in reducing airway responsiveness.

PMID- 12226018
TI  - Predictors of methacholine responsiveness in a general population.
AB  - OBJECTIVE: Methacholine responsiveness is an end point widely used in
      epidemiologic studies of asthma. This study aims to quantify the relative
      importance of different predictors of responsiveness such as age, sex, airway
      caliber, smoking and atopic status, and potential interactions deserving further
      investigation. METHODS: Methacholine challenge was performed in 7,126
      participants (aged 18 to 60 years) of the Swiss Study on Air Pollution and Lung
      Diseases in Adults according to the European Respiratory Health Survey protocol.
      Responsiveness was quantified by the slope between percentage decrements in
      FEV(1) and cumulative methacholine dose. Variation of slopes according to sex,
      smoking, and atopy was then examined separately by multivariate regression models
      that controlled for baseline FEV(1). RESULTS: We found a nonlinear relationship
      between methacholine slope and baseline FEV(1) for both sexes, which could be
      well described by a quadratic function. The corresponding curves were almost
      identical in the region of overlap for male and female neversmokers. Methacholine
      responsiveness declined with age. The slope of this decline was less steep among
      nonatopic persons and nonsmokers compared with atopic neversmokers. Methacholine
      responsiveness increased with the number of cigarettes smoked per day and with
      the number of positive skin-prick test results (except among heavy smokers).
      CONCLUSIONS: Our multiple regression results show that bronchial responsiveness
      (BR) varies with age, FEV(1), and smoking and atopic status. They suggest that
      there is a physiologic basis for the univariate sex difference in BR. Secondly,
      they show that while smaller airways are more responsive than larger ones, the
      reduction of responsiveness diminishes with each increase of lung size. The
      quantification of the relative influence of the different factors examined should
      help in the interpretation of BR.

PMID- 12226019
TI  - Value of a negative aeroallergen skin-prick test result in the diagnosis of
      asthma in young adults: correlative study with methacholine challenge testing.
AB  - BACKGROUND: None of the existing tests for the diagnosis of asthma are considered
      to be definitive. Certain circumstances require prompt diagnosis, and a test able
      to predict the absence of asthma would be very useful. OBJECTIVE: To evaluate the
      contribution of a skin-prick test (SPT) to the diagnostic workup of subjects with
      suspected asthma. PATIENTS AND METHODS: The study included three groups of
      subjects aged 18 to 24 years: group A, asthmatic patients (n = 175); group B,
      control subjects (n = 100); and group C, subjects with suspected asthma (n = 150)
      with normal spirometry findings and a negative exercise challenge test result.
      All underwent an SPT to a battery of common aeroallergens, and group C underwent
      a methacholine challenge test (MCT) in addition. The sensitivity, specificity,
      positive predictive value, and negative predictive values (NPV) of the SPT were
      calculated using provocative concentrations of methacholine causing a 20% fall in
      FEV(1) (PC(20)) of < 4 mg/mL and < 8 mg/mL as diagnostic cutoff values for asthma
      in the MCT. Bayes' formula was used to determine posttest probabilities of having
      asthma, both for positive and negative SPT results. RESULTS: A positive SPT
      result to at least one allergen was found in 95.5%, 54%, and 69% of patients in
      the three groups, respectively. The sensitivity, specificity, and NPV of the SPT
      were 90.7%, 52.0%, and 84.8%, respectively, with a cutoff value of PC(20) < 8
      mg/mL. The lower cutoff, PC(20) < 4 mg/mL, increased the sensitivity and NPV to
      98.2% and 97.8%, respectively. A negative SPT result decreased the probability of
      having asthma by 10-fold to 20-fold in subjects whose pretest probability was low
      to moderate. CONCLUSIONS: Incorporating an SPT into the workup of subjects with
      suspected asthma can reduce the cost of this process significantly. The SPT may
      be used as a simple, fast, safe, inexpensive, and reliable method to predict the
      absence of asthma in young adults.

PMID- 12226020
TI  - Environmental tobacco smoke exposure during travel among adults with asthma.
AB  - OBJECTIVES: In California, state law now prohibits smoking in most public places.
      We examined the prevalence and short-term health impact of environmental tobacco
      smoke (ETS) exposure during travel among adults with asthma. DESIGN, SETTING, AND
      PARTICIPANTS: A cohort of 374 nonsmoking adults with asthma recruited from a
      random sample of allergy, pulmonary, and family practice physicians in northern
      California underwent structured telephone interviews. MEASUREMENTS AND RESULTS:
      The prevalence of self-reported ETS exposure during travel in the past 12 months
      was substantial (30%; 95% confidence interval, 25 to 35%). Of the exposed
      subjects, approximately one third (34%) indicated no other regular source of ETS
      exposure. ETS-related cough, wheezing, or chest tightness during travel was the
      most common complaint (66%), followed by eye irritation (46%) and nose irritation
      (43%). After ETS exposure, many subjects indicated extra inhaled asthma
      medication use (55%). Subjects with no other regular ETS exposure reported a
      greater likelihood of eye irritation (58% vs 40%; p = 0.068) and nose irritation
      (58% vs 36%; p = 0.025) than persons with regular exposure. In contrast, there
      were no differences in respiratory symptoms, asthma medication use, or asthma
      exacerbation by regular ETS exposure status. CONCLUSIONS: In adults with asthma,
      ETS exposure is common during travel. For many subjects, travel is their
      principal source of exposure.

PMID- 12226021
TI  - Body fat distribution, serum leptin, and cardiovascular risk factors in men with
      obstructive sleep apnea.
AB  - STUDY OBJECTIVE: s: To determine whether traditional risk factors for
      cardiovascular disease (CVD) and regional fat distribution, especially the
      central obesity type and increased parapharyngeal fat pads, are associated with
      the degree of obstructive sleep apnea (OSA). To determine whether there are
      interrelationships between body fat, serum leptin levels, and the degree of OSA.
      DESIGN AND SETTING: Prospective mono-center cross-sectional study in a university
      hospital in Germany. PATIENTS: Eighty-five consecutive male patients who were
      referred for evaluation of suspected OSA. MEASUREMENTS AND RESULTS: The major
      dependent outcome variable was the apnea-hypopnea index (AHI), the average number
      of apneas and hypopneas per hour of sleep, determined by overnight
      polysomnography. Independent measures were anthropometric data, body composition
      analysis (bioelectrical impedance analysis [BIA]), cardiovascular risk factor
      evaluation (smoking, hypertension, serum lipoproteins, diabetes or impaired
      glucose tolerance, uric acid, fibrinogen), and leptin. Adipose tissue
      quantification of the abdominal and neck regions was performed by nuclear MRI
      (NMR). Significant linear relationships of AHI with fasting blood glucose, uric
      acid, fibrinogen, body weight, body mass index (BMI), sum of fat skin folds, and
      percentage of body fat could be established, whereas there was no correlation
      with age. The presence of OSA was independent of smoking, hypertension, and
      lipoproteins. NMR scans showed that AHI was significantly correlated with intra
      abdominal fat and subcutaneous abdominal fat, whereas subcutaneous fat in the
      neck region and parapharyngeal fat in the airway vicinity were not correlated.
      Leptin concentrations correlated with AHI and with biochemical markers of the
      metabolic syndrome (lipoproteins, glucose) but were not dependent on AHI.
      Logistic regression analysis found percentage of body fat (BIA) and BMI as good
      predictors of AHI > 10 with a sensitivity of 95.5% but a low specificity (46.2%).
      Multiple regression analysis identified the sum of fat skin folds, body weight,
      and BMI as good predictors for the degree of OSA. CONCLUSIONS: We conclude that
      OSA is independent from most traditional risk factors for CVD. Regional body fat
      distribution predicts the presence and degree of OSA, but fat accumulation in the
      neck and parapharyngeal region are of minor importance. Leptin concentrations
      when controlled for body fat are not related to the degree of OSA.

PMID- 12226022
TI  - Anatomic determinants of sleep-disordered breathing across the spectrum of
      clinical and nonclinical male subjects.
AB  - OBJECTIVES: We wished to determine the independent contribution of craniofacial
      dimensions of the upper airway to sleep-disordered breathing (SDB) in subjects
      who spanned the entire continuum of SDB. We also determined the interactive
      effects of body mass index (BMI) and age on the relationship between airway
      dimensions and SDB. DESIGN AND SUBJECTS: We studied 142 nonclinical male subjects
      in a working community population (average age, 47 years; average BMI, 29;
      average +/- SD apnea/hypopnea index [AHI], 20 +/- 20/h), and 62 patients with
      obstructive sleep apnea (average age, 47 years; average BMI, 32; average +/- SD
      AHI, 48 +/- 35/h. We determined the AHI from overnight polysomnography and the
      number of oxygen desaturations (> or = 2%) per hour of sleep. We used lateral
      facial cephalometric radiographs to measure 41 anatomic landmarks and 55
      dimensions in the upper airway. SETTING: A university hospital and a sleep
      disorders clinic. DATA ANALYSIS: We used stepwise regression analysis to
      determine the independent contributions of measured variables to SDB.
      MEASUREMENTS AND RESULTS: In the entire study population (n = 204), variations in
      BMI and six measures of craniofacial morphology accounted equally for one half of
      the total variance in AHI, and their interactive effects accounted for an
      additional 15%. Membership in the clinical or nonclinical group per se had no
      significant influence on these relationships. The single most important
      cephalometric variable in predicting AHI severity was the horizontal dimension of
      the maxilla (ie, porion vertical to supradentale [PV-A] distance). When the PV-A
      distance was relatively narrow (< 97 mm) the probability of having mild (AHI, 15
      to 30/h) to severe (AHI > 30/h) SDB increased fivefold to sevenfold in nonobese
      subjects and threefold in obese subjects. Thus, in nonobese subjects (average
      BMI, 25 +/- 2) and in subjects with narrow upper airway dimensions, four
      cephalometric dimensions were the dominant predictors of AHI, accounting for 50%
      of the variance. However, in subjects with a large anteroposterior facial
      dimension, BMI was the major predictor of AHI and a BMI > 28 increased the
      probability of moderate-to-severe sleep apnea by approximately fivefold. Finally,
      the combination of cephalometric dimensions and BMI accounted for an increasing
      amount of the variance in AHI as the severity of AHI increased. CONCLUSIONS:
      Across the population spectrum of SDB, four cephalometric dimensions of the upper
      airway in combination with BMI accounted independently for up to two thirds of
      the variation in AHI; and the relative contribution of these two sets of
      determinants of AHI varied depending on airway size, obesity, and the amount of
      SDB.

PMID- 12226023
TI  - Prevalence of sleep-disordered breathing and continuous positive airway pressure
      compliance: results in chinese patients with first-ever ischemic stroke.
AB  - OBJECTIVE: To assess the prevalence of sleep-disordered breathing (SDB),
      continuous positive airway pressure (CPAP) acceptance, and CPAP compliance in
      patients who have experienced ischemic stroke. DESIGN: A case-controlled study.
      SETTING: A university hospital. MEASUREMENTS AND RESULTS: We recruited 23 women
      and 28 men, who were admitted to the hospital within 4 days of stroke onset, with
      a mean (+/- SD) age of 64.2 +/- 13.0 years and a body mass index (BMI) of 24.3 +/
      4.4 kg/m(2) for this study. Twenty-seven patients (53%) and 9 patients (17.6%),
      respectively, reported a history of snoring and severe daytime sleepiness prior
      to experiencing a stroke, while the mean Epworth sleepiness scale score was 6.8
      +/- 3.6. Polysomnography revealed 34 patients (67%) with an apnea-hypopnea index
      (AHI) of > or = 10 events per hour, 31 patients (61%) with an AHI of > or = 15
      events per hour, and 25 patients (49%) with an AHI of > or = 20 events per hour.
      Significant obstructive SDB, defined as an AHI of > or = 20/h, was more prevalent
      in ischemic stroke patients than in control subjects (49% vs 24%, respectively; p
      = 0.04) and was associated with a higher BMI (p = 0.046). Among the 34 patients
      with an AHI of > or = 10/h, CPAP titration was tolerated by 16 patients, but only
      4 patients who had typical sleep apnea features proceeded to home CPAP treatment
      with objective compliance over a period of 3 months of 2.5 +/- 0.6 h per night. A
      subgroup of 20 patients not receiving CPAP showed partial spontaneous improvement
      of SDB at 1 month (baseline AHI, 32.3 +/- 17.6 events per hour; AHI at 1 month,
      23.0 +/- 18.8 events per hour; p = 0.01) with a trend toward improvement for the
      obstructive but no significant change for the central events, whereas no
      improvement in AHI was noted for the four patients receiving CPAP. CONCLUSION:
      There is a high prevalence of obstructive SDB in patients who have experienced
      acute ischemic stroke, which, in many cases, is different from classic
      obstructive sleep apnea syndrome, and this is reflected by the lack of
      significant sleepiness, poor CPAP acceptance, and partial spontaneous improvement
      at 1 month.

PMID- 12226024
TI  - Relationship between quality of life and mood or depression in patients with
      severe obstructive sleep apnea syndrome.
AB  - STUDY OBJECTIVES: To assess the quality of life (QOL) in patients with severe
      obstructive sleep apnea (OSAS), and the relationship between the QOL and severity
      of OSAS, excessive daytime sleepiness (EDS), and mood. METHODS: Sixty patients
      with OSAS and 34 normal control subjects were assessed for QOL using the Medical
      Outcomes Study Short-Form 36 Health Survey questionnaire (SF-36), for EDS using
      the Epworth sleepiness scale (ESS), and for mood using the Zung self-rated
      depression scale (SDS). The associations between each domain and the total score
      on the SF-36 and the baseline characteristics, polysomnographic parameters, ESS
      score, and SDS score were examined by simple regression analysis and stepwise
      multiple regression analysis. RESULTS: Six of eight domains and the total score
      on the SF-36 were significantly lower than those in the control subjects. The ESS
      and SDS scores were also more impaired in the patients than in the control
      subjects. There was no relationship between each domain on the SF-36 and the
      severity of OSAS and ESS score. Five of eight domains and the total score on the
      SF-36 were significantly correlated with the SDS score. Stepwise multiple
      regression analysis selected three variables, the SDS score (partial R(2) =
      0.505), the lowest arterial oxygen saturation during sleep (partial R(2) =
      0.064), and ESS score (partial R(2) = 0.053), as independent factors for
      predicting the total score on the SF-36. These three variables accounted for
      62.2% of the total variance in the total score on SF-36 (R(2) = 0.622, p <
      0.0001) CONCLUSIONS: The QOL of patients with severe OSAS was decreased compared
      with normal control subjects. The QOL of patients was strongly correlated with
      the depression scale on simple regression analysis. However, EDS score and oxygen
      desaturation during sleep also affected the QOL, although the magnitude of its
      effect was small.

PMID- 12226025
TI  - Two-point palatal discrimination in patients with upper airway resistance
      syndrome, obstructive sleep apnea syndrome, and normal control subjects.
AB  - STUDY OBJECTIVE: To compare the results of a two-point palatal discrimination
      response in normal subjects (n = 15), patients with obstructive sleep apnea
      syndrome (OSAS) [n = 15], and patients with upper airway resistance syndrome
      (UARS) [n = 15] matched for age, sex, and body mass index. DESIGN: Comparison
      study of three subject groups. SETTING: A sleep-disorders clinic. SUBJECTS:
      Participants were selected based on clinical questionnaire, clinical evaluation,
      and polysomnography. INTERVENTION: Polysomnography involving measurement of flow
      limitation with a nasal cannula pressure transducer system and of respiratory
      effort with esophageal pressure was performed in order to recognize the presence,
      absence, and types of sleep-disordered breathing. The 45 subjects were submitted
      to a two-point palatal discrimination study during wakefulness performed by an
      investigator blinded to the polysomnogram results. RESULTS: Patients with OSAS
      had a clear impairment of their palatal sensory input with a significant
      decrement in two-point discrimination, but patients with UARS and normal control
      subjects had similar responses. Patients with UARS exhibited at least
      intermittent snoring in most cases. CONCLUSION: The normal responses seen in
      patients with UARS indicate that these patients are more capable of transmitting
      sensory inputs than patients with OSAS. This may be one element explaining the
      difference in arousal response previously documented in UARS compared to OSAS.

PMID- 12226026
TI  - Occlusal and skeletal effects of an oral appliance in the treatment of
      obstructive sleep apnea.
AB  - STUDY OBJECTIVE: s: Oral appliances (OAs) are considered to be a treatment option
      for patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). Although the
      effectiveness of these appliances has been evaluated in a number of clinical
      trials, there are few follow-up studies concerning the dental and skeletal side
      effects that, theoretically, could be caused by OAs. We sought to examine the
      long-term skeletal and occlusal effects of a nocturnally worn activator in adult
      patients treated for OSAHS. DESIGN: We analyzed the dental casts and lateral
      radiographs of 34 patients (mean age, 52.9 years; SD, 9.6 years; range, 27.1 to
      64.6 years) before initiating treatment and after at least 24 months of treatment
      (mean length of treatment, 29.6 months; range, 24.1 to 43.5 months; SD, 5.1
      months). The OA was worn by each patient 6 to 8 h nightly for > 5 days per week.
      SETTING: Department of Orthodontics, Dental Medical School, Freiburg, Germany.
      MEASUREMENTS AND RESULTS: Follow-up polysomnography studies confirmed improved
      breathing parameters with the use of OAs. A statistically significant alteration
      in the occlusion was found. The anteroposterior position of the molars and the
      inclination of the upper and lower incisors were changed. No skeletal changes in
      the position of the mandible were noted. CONCLUSIONS: The data suggest that in
      addition to control polysomnographic examinations, regular dental follow-up
      visits are mandatory when lifelong OSAHS treatment with an OA is being considered
      for patients with obstructive sleep apnea/hypopnea.

PMID- 12226027
TI  - The changing pattern of bronchoscopy in an HIV-infected population.
AB  - STUDY OBJECTIVE: s: Little information exists on the impact of antiretroviral
      therapies (ARTs) on HIV-related bronchoscopic activity. This study was performed
      to identify any changes to our pattern of use of bronchoscopy over the last
      decade, and how this might relate to the introduction of more effective ARTs to
      our center in 1996. DESIGN: Retrospective data analysis. SETTING: Academic
      medical center. PATIENTS: HIV-positive patients attending the clinic. METHODS:
      Basic demographic details and bronchoscopy status were collected and compared for
      all patients with HIV attending our center between 1989 and 1998. Poisson
      regression analysis was performed to more formally identify the risk factors for
      bronchoscopy. Individual case notes and bronchoscopic findings were also examined
      for all patients undergoing bronchoscopy in 1990, 1995, and 1998. RESULTS: From
      1996 to 1998, bronchoscopic rates fell dramatically by 60% (p < 0.0001) despite a
      linear increase in patients receiving follow-up. Prior use of protease inhibitor
      (PI)/nonnucleoside reverse transcriptase inhibitor (NNRTI) combinations was
      significantly associated with a decreased risk of bronchoscopy even after
      adjusting for CD4 counts. Indications for bronchoscopy and diagnostic yield
      remained relatively stable in 1990, 1995, and 1998, although rates of pulmonary
      infection (Pneumocystis carinii pneumonia, bacteria, and virus) requiring
      bronchoscopy among our HIV population fell significantly from 1990 to 1998.
      CONCLUSION: Improvements in HIV health care are having a dramatic impact on the
      rates of certain pulmonary infections requiring bronchoscopy. Of these, the
      introduction of more effective ARTs to our service in 1996 seems most closely
      related to the temporal decline in bronchoscopy. PI/NNRTI combinations may have
      additional protective effects to their recognized action on CD4 counts.

PMID- 12226028
TI  - Clinical presentation of pulmonary mycetoma in HIV-infected patients.
AB  - STUDY OBJECTIVE: s: Although pulmonary mycetoma has been well-described in
      immunocompetent hosts, the only description in HIV-infected patients has been of
      10 patients from our institution, from 1992 to 1995. To further investigate the
      impact of HIV status on the presentation and course of pulmonary mycetoma, we
      conducted a follow-up study. DESIGN: Retrospective review of all cases of
      pulmonary mycetoma at Bellevue Hospital from 1992 to 1999. SETTING: Patients were
      evaluated on the inpatient chest service and in the outpatient chest and HIV
      clinics of Bellevue Hospital in New York City. PATIENTS: We identified 74
      patients with pulmonary mycetoma; 20 of them were HIV-infected (27%).
      INTERVENTIONS: The 20 HIV-infected patients were treated with antiretroviral
      and/or antifungal therapy. MEASUREMENTS AND RESULTS: Predisposing diseases were
      pulmonary tuberculosis (TB), Pneumocystis carinii pneumonia (PCP), or both TB and
      PCP. Seventeen patients had a CD4+ cell count of < 100 cells/ micro L at
      presentation. Hemoptysis was present in 13 patients, but was massive in only 1
      patient. Cough was common. Of the 18 patients for whom follow-up was available,
      11 received antifungal treatment and 7 were observed without therapy. Six
      patients received both antiretroviral and antifungal therapy. Disease progression
      occurred in 50%. Only five patients exhibited radiographic or clinical
      improvement. All five were treated with both antiretroviral and antifungal
      therapy. CONCLUSIONS: PCP is a risk factor for pulmonary mycetoma in the HIV
      infected individual. HIV-infected patients with mycetomas have a significant rate
      of disease progression, although they rarely have life-threatening hemoptysis. A
      combination of antifungal and antiretroviral therapy may improve the clinical
      outcome in HIV-infected patients with pulmonary mycetoma.

PMID- 12226029
TI  - Technical and prognostic outcomes of double-balloon pericardiotomy for large
      malignancy-related pericardial effusions.
AB  - OBJECTIVE: To investigate both the use of immediate or elective double-balloon
      pericardiotomy (DBP) in patients with a large amount of malignancy-related
      pericardial effusion, and the prognosis of this subgroup. DESIGN: Observational
      study after DBP intervention. SETTING: Tertiary referral center. PATIENTS AND
      INTERVENTIONS: Fifty patients with malignancy, mainly lung and breast cancer, who
      were admitted to our critical care unit with a large amount of pericardial
      effusion. All received echocardiographic-guided pericardiocentesis. Group 1
      consisted of 12 patients (24%) who received immediate DBP, and group 2 consisted
      of 38 patients (76%) who received delayed DBP 2.5 +/- 1.7 days later (mean +/-
      SD) after emergency pericardiocentesis with pigtail catheter drainage.
      MEASUREMENTS: After the procedure, and at 1 month, 3 months, and 6 months,
      echocardiography and chest radiography were performed to check for pneumothorax,
      pericardial effusion reaccumulation, or the appearance of pleural effusion after
      pigtail catheter removal. MAIN RESULTS: The procedure was successful and without
      recurrence in 44 patients (88%). Procedural complications were fever in 4
      patients (33%) and 10 patients (26%) in group 1 and group 2, respectively (p =
      0.72), and mild pneumothorax in 2 patients (17%) and 1 patient (3%) in group 1
      and group 2, respectively (p = 0.14). Fifty percent of the patients died within 4
      months, while 25% survived to 11 months. High serum calcium, a low
      albumin/globulin ratio, and positive results on pericardial effusion cytology
      were poor prognostic factors for long-term survival. CONCLUSION: Both immediate
      and delayed DBP are a safe and effective method of relieving large pericardial
      effusions in patients with cancer. Successful DBP without recurrence of
      pericardial effusion was achieved in 88% of all patients. Survival was related to
      the extent of the disease.

PMID- 12226030
TI  - The use of adenosine deaminase and interferon-gamma as diagnostic tools for
      tuberculous pericarditis.
AB  - BACKGROUND: Traditional diagnostic tests for pericardial tuberculosis (TB) are
      insensitive and often require long culture periods, and this has led to more
      emphasis being placed on biochemical tests such as the pericardial adenosine
      deaminase (ADA) test. However, controversy exists as to its diagnostic utility.
      In addition, the use of interferon (IFN)-gamma, which is a reliable indicator of
      pleural and peritoneal TB, has not been explored in pericardial effusions. We
      investigated ADA and IFN-gamma levels in pericardial effusions of different
      etiologies. METHODS AND RESULTS: A prospective study was carried out from
      February 1995 to February 1998 at Tygerberg Hospital (South Africa), with
      pericardial taps being performed under echocardiographic guidance. During this
      period, 110 consecutive patients presenting with large pericardial effusions were
      included in the study. Diagnoses were made according to predetermined criteria,
      and they included TB (n = 64), malignancy (n = 12), nontuberculous infections (n
      = 5), other effusions (n = 19), and effusions of uncertain origin (n = 10). The
      median ADA level in the tuberculous group was 71.7 U/L (range, 10.3 to 303.6
      U/L), which was significantly higher than that in any other group (p < 0.05).
      With a cutoff level for ADA activity of 30 U/L, sensitivity was 94%, specificity
      was 68%, and positive predictive value was 80%. IFN-gamma levels were determined
      in 30 subjects. The median IFN-gamma concentration in the tuberculous group was >
      1,000 pg/L, which was significantly higher than in any other diagnostic group (p
      < 0.0005). A cutoff value of 200 pg/L for IFN-gamma resulted in a sensitivity and
      specificity of 100% for the diagnosis of pericardial TB. CONCLUSION: Pericardial
      fluid levels of ADA and IFN-gamma are useful in the diagnosis of tuberculous
      pericarditis.

PMID- 12226031
TI  - Improving care for patients with chronic heart failure in the community: the
      importance of a disease management program.
AB  - STUDY OBJECTIVE: Utilizing a comparison group of patients with congestive heart
      failure (CHF) discharged to their primary care physicians, we sought to determine
      if disease management in a short-term, aggressive-intervention heart failure
      clinic (HFC) following hospital discharge is associated with improved outcomes.
      DESIGN: Chart review. SETTING: An integrated health-care center serving a
      tristate area. PATIENTS: Inclusion criteria were discharge from the hospital with
      a primary diagnosis of CHF, outpatient follow-up within the hospital system, and
      the presence of left ventricular systolic dysfunction as the basis for CHF.
      Patients were categorized into group 1 if they were referred to the HFC after
      hospital discharge, and into group 2 if follow-up care was provided by their
      primary care physician. MEASUREMENTS AND RESULTS: There were 38 patients in group
      1 and 63 patients in group 2. There was a trend toward a shorter time to the
      first outpatient visit following discharge (11 days vs 15 days, p = 0.09), more
      outpatient visits within 90 days (10 visits vs 2 visits, p < 0.001), and more
      patient-initiated contacts (four contacts vs one contact, p = < 0.001) in group 1
      compared to group 2, respectively. The combined hospital readmission and
      mortality rate at 90 days (10% vs 30%, p < 0.018) and 1 year (21% vs 43%, p <
      0.02) was lower in group 1. There was a 77% relative risk reduction for 30-day
      hospital readmission in favor of group 1, and a statistically lower rate of
      readmissions at 90 days and 1 year. Utilization and maintenance of standardized
      CHF medications were significantly higher in patients who attended the HFC.
      CONCLUSIONS: A comprehensive disease management program for patients discharged
      with a diagnosis of CHF resulted in fewer rehospitalizations and improved event
      free survival compared to patients followed up by their primary care physicians.

PMID- 12226032
TI  - An intervention to improve antibiotic delivery and sputum procurement in patients
      hospitalized with community-acquired pneumonia.
AB  - STUDY OBJECTIVES: To determine if an educational intervention targeting emergency
      department (ED) and medicine staff could successfully decrease the time to
      antibiotic delivery (door-to-drug delivery time [DDD]) for patients admitted
      through the ED with community-acquired pneumonia (CAP). DESIGN: Prospective,
      multidisciplinary team-based educational project. Demographics, outcomes, and
      processes of care including DDD and sputum procurement for patients with CAP were
      determined during a baseline period and compared to the same parameters for
      patients with CAP presenting after the educational intervention was administered
      to ED and medicine staff. SETTING: Barnes-Jewish Hospital, a large Midwest
      teaching institution affiliated with the Washington University School of
      Medicine. PATIENTS: Consecutive adult patients admitted through the ED with CAP.
      INTERVENTION: Multidisciplinary in-service education administered to ED
      physicians and nurses, and medicine housestaff, which emphasized the importance
      of rapid antibiotic delivery and procurement of preantibiotic expectorated
      sputum. RESULTS: Mean DDD improved from 413 to 291 min (p = 0.02), with more
      patients receiving antibiotics in the ED (46% vs 69%; adjusted odds ratio [OR],
      2.3; 95% confidence interval [CI], 1.0 to 4.9). Sputum procurement improved from
      11.5 to 25.4% (adjusted OR, 3.3; 95% CI, 1.1 to 9.9). There were no observed
      differences for inpatient mortality or length of stay. CONCLUSION: This
      multidisciplinary team intervention significantly improved the time to initiation
      of antibiotics and procurement of sputum for patients with CAP.

PMID- 12226033
TI  - The community-acquired pneumonia symptom questionnaire: a new, patient-based
      outcome measure to evaluate symptoms in patients with community-acquired
      pneumonia.
AB  - STUDY OBJECTIVE: s: To develop and validate a patient-based outcome measure to
      evaluate symptoms in patients with community-acquired pneumonia (CAP). DESIGN: A
      psychometric study within an international, prospective, randomized, double-blind
      study. The CAP-symptom questionnaire (CAP-Sym) is a new, 18-item, patient
      reported outcome measure that evaluates the bothersomeness of CAP-related
      symptoms during the past 24 h using a 6-point Likert scale. We used "gold
      standard" psychometric methods to comprehensively evaluate the acceptability,
      reliability, validity, and responsiveness of the CAP-Sym. SETTING: Sixty-four
      centers in 13 countries (France, Germany, Hungary, Israel, Italy, Norway, Poland,
      Portugal, South Africa, Spain, Sweden, Switzerland, United Kingdom). PATIENTS:
      Five hundred fifty-six patients with CAP, recruited from outpatient clinics,
      general practice, and hospital centers. INTERVENTIONS: Randomization 1:1 to
      moxifloxacin (400 mg once daily), oral or standard oral treatment (amoxicillin, 1
      g tid, or clarithromycin, 500 mg bid), alone or in combination, for up to 14
      days. RESULTS: Standard psychometric tests confirmed the acceptability (item
      nonresponse, item-endorsement frequencies, item/scale floor and ceiling effects),
      reliability (internal consistency, item-total and inter-item correlations, test
      retest reliability), validity (content, construct, convergent, discriminant,
      known groups), and responsiveness of the CAP-Sym. CONCLUSIONS: The CAP-Sym is a
      practical and scientifically sound patient-based outcome measure of CAP-related
      symptoms that has been developed using "gold standard" methods. As the only fully
      validated measure of symptoms in patients with CAP, which is quick and easy to
      administer and is more responsive than the generic Medical Outcomes Study 36-Item
      Short-Form Health Survey, the CAP-Sym provides a practical and rigorous method
      for improving the evaluation of outcomes in clinical trials and audit.

PMID- 12226034
TI  - Evaluation of bronchial constriction in children with cystic fibrosis after
      inhaling two different preparations of tobramycin.
AB  - OBJECTIVES: This randomized, double-blind, cross-over study evaluated the risk of
      bronchoconstriction with two preparations of inhaled tobramycin in children with
      cystic fibrosis (CF) infected with Pseudomonas aeruginosa with and without airway
      hyperreactivity. DESIGN: Of 19 children with CF (age range, 7 to 16 years) with
      mild-to-moderate pulmonary disease, 10 children were at high risk (HR) for
      bronchospasm (family history of asthma and previous response to bronchodilators)
      and 9 children were at low risk (LR) for bronchospasm (no family history of
      asthma or previous response to bronchodilators). Two solutions of tobramycin were
      administered: (1) 80 mg in a 2-mL vial diluted with 2 mL of saline solution
      containing the preservatives phenol and bisulfites (IV preparation); and (2) 300
      mg in a preservative-free preparation in a 5-mL solution. Following a
      bronchodilator-free period of 12 h, the patients inhaled either one or the other
      preparation in random order on two different occasions, 2 weeks apart. RESULTS:
      Prechallenge and postchallenge results for the LR group showed a percentage of
      fall in FEV(1) (DeltaFEV(1)) of 12 +/- 9% (mean +/- SD) for the IV preparation,
      compared to 4 +/- 5% for the preservative-free preparation (p = 0.046). An
      DeltaFEV(1) of > 10% was seen in six of nine patients for the IV preparation and
      in one of nine patients for preservative-free preparation. For the HR group, the
      DeltaFEV(1) was 17 +/- 13% for the IV-preparation group, compared to 16 +/- 12%
      for the preservative-free group (p = 0.4). In this group, equal numbers of
      patients (8 of 10 patients) had an DeltaFEV(1) > 10% after inhaling each
      preparation. The largest DeltaFEV(1) was 44% (HR group with the preservative-free
      preparation that forced the early termination of inhalation). CONCLUSIONS: Both
      preparations caused significant bronchoconstriction in the HR group, and the
      preservative-containing IV preparation caused more bronchospasm in LR group than
      the preservative-free solution. Heightened airway reactivity in children with CF
      places them at risk of bronchospasm from inhalation therapy.

PMID- 12226035
TI  - Early ribavarin treatment of bronchiolitis: effect on long-term respiratory
      morbidity.
AB  - BACKGROUND: The mortality rate from respiratory syncytial virus (RSV)
      bronchiolitis has significantly reduced over the last decade. A major concern now
      is the long-term respiratory morbidity following RSV bronchiolitis. METHODS: In
      this prospective study, we randomly assigned 49 previously healthy infants with
      severe RSV bronchiolitis, early in the course of illness (< 5 days duration), to
      receive either conservative treatment (n = 21) or additional ribavirin treatment
      (n = 24). Both groups were closely matched for age and clinical characteristics.
      RESULTS: During a prospective, closely monitored, 1-year follow-up period, the
      group treated with ribavirin had significantly fewer episodes (2.7 +/- 2.3
      episodes vs 6.4 +/- 4.2 episodes per patient per year) and reduced severity of
      reactive airway disease (0.08 episodes vs 1.09 episodes of moderate-to-severe
      illness per patient per year) and respiratory illness-related hospitalization (25
      hospital days vs 90 hospital days per 100 patients per year). CONCLUSIONS: Early
      ribavirin treatment of RSV bronchiolitis in previously healthy infants resulted
      in reduction of incidence and severity of reactive airway disease as well as
      respiratory illness-related hospitalization.

PMID- 12226036
TI  - Modifications of airway responsiveness to adenosine 5'-monophosphate and exhaled
      nitric oxide concentrations after the pollen season in subjects with pollen
      induced rhinitis.
AB  - STUDY OBJECTIVE: s: To determine the effect of cessation of exposure to pollen on
      airway responsiveness to adenosine 5'-monophosphate (AMP) in subjects with pollen
      induced rhinitis, and to explore the relationship between changes in airway
      responsiveness and changes in exhaled nitric oxide (ENO) levels. STUDY DESIGN:
      Subjects were studied during the pollen season and out of season. SETTING:
      Specialist allergy unit in a university hospital. PATIENTS: Fourteen subjects
      without asthma with pollen-induced rhinitis who showed bronchoconstriction in
      response to methacholine and AMP during the pollen season and 10 healthy
      nonatopic control subjects. MEASUREMENTS AND RESULTS: In subjects with pollen
      induced rhinitis, ENO concentrations, provocative concentration of agonist
      causing a 20% fall in FEV(1) (PC(20)) methacholine, and PC(20) AMP were
      determined during the pollen season and out of season. Healthy control subjects
      were studied during the pollen season. In subjects with allergic rhinitis, PC(20)
      AMP increased from a geometric mean of 79.4 mg/mL (95% confidence interval [CI],
      31.6 to 199.5 mg/mL) during the pollen season to 316.2 mg/mL (95% CI, 158.5 to
      400.0 mg/mL) out of season (p = 0.004). The ENO concentrations decreased from
      63.1 parts per billion (ppb) [95% CI, 50.1 to 79.4 ppb] during the pollen season
      to 30.2 ppb (95% CI, 23.4 to 38.0 ppb) out of season (p < 0.001). The ENO
      concentrations out of pollen season were still significantly increased in
      subjects with pollen-induced rhinitis when compared with healthy control
      subjects. There was no relationship between individual changes in ENO levels and
      changes in either PC(20) methacholine or PC(20) AMP. CONCLUSIONS: In pollen
      sensitive subjects with allergic rhinitis, the cessation of exposure to pollen is
      associated with a significant reduction of airway responsiveness to inhaled AMP.
      However, no association was found between allergen-induced changes in ENO values
      and in airway responsiveness to either direct or indirect bronchoconstrictors.
      These findings suggest that modifications in ENO and in airway responsiveness are
      the consequence of different alterations induced by allergen exposure on the
      lower airways.

PMID- 12226037
TI  - Exercise maintenance following pulmonary rehabilitation: effect of distractive
      stimuli.
AB  - STUDY OBJECTIVE: To determine if distractive auditory stimuli (DAS) in the form
      of music would promote adherence to a walking regimen following completion of a
      pulmonary rehabilitation program (PRP) and, thereby, maintenance of gains
      achieved during the program. DESIGN: Experimental, randomized, two-group design
      with testing at baseline, 4 weeks, and 8 weeks. SETTING: Outpatient. PATIENTS:
      Twenty-four patients (4 men and 20 women) with moderate-to-severe COPD (FEV(1)
      41.3 +/- 13% predicted [mean +/- SD]). INTERVENTION: Experimental group subjects
      (n = 12) were instructed to walk at their own pace for 20 to 45 min, two to five
      times a week, using DAS with a portable audiocassette player. The control group
      (n = 12) received the same instructions, but no DAS. MEASUREMENTS AND RESULTS:
      Primary outcome measures were perceived dyspnea during activities of daily living
      (ADL) and 6-min walk (6MW) distance. Secondary outcome measures were anxiety,
      depressive symptoms, health-related quality of life (QoL), global QoL, and
      breathlessness and fatigue at completion of the 6MW. In addition, all subjects
      recorded the distance and time walked using self-report (pedometers and daily
      logs). There was a significant decrease in perceived dyspnea during ADL (p =
      0.0004) and a significant increase in 6MW distance (p = 0.0004) over time in the
      DAS group compared to the control group. DAS subjects increased 6MW distance 445
      +/- 264 feet (mean +/- SD) from baseline to 8 weeks, whereas control subjects
      decreased 6MW distance to 169 +/- 154 feet. No significant differences were noted
      for the remaining variables. The cumulative distance walked by the DAS group was
      19.1 +/- 16.7 miles compared to 15.4 +/- 8.0 miles for the control group, a 24%
      difference (p = 0.49). Despite this difference, self-report exercise log data
      were similar for the two groups. CONCLUSION: Subjects who used DAS while walking
      had improved functional performance and decreased perceptions of dyspnea, whereas
      control subjects could not maintain post-PRP gains. DAS is a simple, cost
      effective strategy that may have the potential to augment the effectiveness of
      post-PRP maintenance training.

PMID- 12226038
TI  - Comparison of sputum induction using high-output and low-output ultrasonic
      nebulizers in normal subjects and patients with COPD.
AB  - STUDY OBJECTIVE: s: Induced sputum is used to investigate pulmonary diseases. Low
      output ultrasonic nebulizers have become available and have potential advantages
      over high-output nebulizers. We hypothesized that a low-output nebulizer would
      give comparable results to a high-output nebulizer, with an acceptable safety
      profile. DESIGN: Randomized, crossover study. SETTING: University teaching
      hospital. PARTICIPANTS: Ten normal subjects and 10 patients with COPD.
      INTERVENTIONS: Participants attended for sputum induction on two occasions in
      random order using low-output and high-output nebulizers. MEASUREMENTS AND
      RESULTS: Lung function and oxygen saturation were measured during sputum
      induction, and tolerability of the procedure was assessed. Cell counts,
      interleukin 8, and neutrophil elastase were measured in sputum. Use of the high
      output nebulizer resulted in a greater FEV(1) (mean +/- SEM, 0.29 +/- 0.04 L vs
      0.21 +/- 0.04 L; p = 0.04) and percentage drop in FEV(1) (25.8 +/- 2.6% vs 19.5
      +/- 2.9%, respectively; p = 0.02) compared with the low-output nebulizer in
      patients with COPD. There was a shorter tolerated nebulization time with the high
      output nebulizer compared with the low-output nebulizer: 12.7 +/- 2.0 min vs 16.5
      +/- 1.8 min, respectively (p = 0.02). Modified Borg scores were lower with the
      low-output nebulizer than the high-output nebulizer in normal subjects: median, 0
      (interquartile range [IQR], 0 to 1) vs median, 1.5 (IQR, 0 to 2), respectively (p
      = 0.05). There were no differences in cell counts and soluble markers of
      inflammation. CONCLUSIONS: The low-output ultrasonic nebulizer is comparable to
      high-output nebulizer for cellular and soluble markers of inflammation, results
      in a smaller reduction in FEV(1), is better tolerated, and is a suitable tool for
      investigating airway inflammation in patients with COPD.

PMID- 12226039
TI  - Deep venous thrombosis in a general hospital.
AB  - PURPOSE: To determine the prevalence of proximal deep venous thrombosis (DVT) in
      a general hospital. BACKGROUND: In spite of the importance of proximal DVT, its
      prevalence in hospitalized patients has been only sparsely studied. METHODS:
      Patients hospitalized with DVT between July 1998 and June 2000 were identified by
      a computer search of discharge diagnoses. The discharge diagnosis was confirmed
      by a review of the records for positive findings on compression ultrasound or
      venogram of the lower extremities. In addition, records of all compression
      ultrasound examinations and venograms during that period were examined. RESULTS:
      The prevalence of proximal DVT in adults > or = 20 years old was 271 of 34,567
      patients (0.78%). DVT was associated with pulmonary embolism in 57 of 271
      patients (21.0%). The prevalence of DVT in adult men was 117 of 13,722 patients
      (0.85%), and in adult women was 154 of 20,845 patients (0.74%) [not significant].
      The prevalence of DVT among men aged 20 to 49 years was higher than in women the
      same age: 19 of 3,982 patients (0.48%) vs 22 of 9,442 patients (0.23%),
      respectively (p < 0.02). The prevalence of DVT, however, was comparable among men
      and women > or = 50 years old. The prevalence of DVT was also comparable in black
      adults (30 of 4,344 patients; 0.69%) and in white adults (240 of 28,615 patients;
      0.84%) [not significant]. CONCLUSION: Proximal DVT continues to be a frequent
      illness among hospitalized patients.

PMID- 12226040
TI  - Medical literature and vena cava filters: so far so weak.
AB  - STUDY OBJECTIVE: With the development of percutaneous inferior vena cava (IVC)
      filters, IVC interruption has become a widely used procedure in patients with or
      at risk for venous thromboembolism. In an attempt at clarifying the indications
      for filter placement, a systematic literature review was undertaken. DESIGN:
      Bibliographic search and analysis. MEASUREMENTS AND RESULTS: A systematic MEDLINE
      search about vena cava filters produced a total of 568 references with abstracts
      between 1975 and 2000 inclusively. Each reference was analyzed according to
      predetermined criteria. Nearly two thirds (65.0%) of these publications were
      retrospective studies or case reports (33.3 and 31.7%, respectively), 12.9% were
      animal or in vitro studies, 7.4% were prospective studies, 6.7% were reviews, and
      8.1% reported on miscellaneous related topics. Among the prospective studies,
      only 16 studies included > or = 100 patients, only 1 study was a randomized
      controlled trial (0.02% of 568 references), and heterogeneity among series
      precluded any relevant comparison. In a similar search about heparin and venous
      thromboembolism, 47.4% of 531 references were randomized controlled trials.
      CONCLUSIONS: Until more relevant data become available, literature reviews about
      vena cava filters will remain narrative, and many if not most indications for
      filter placement will remain a matter of opinion.

PMID- 12226041
TI  - Acute pulmonary thromboembolism: comparison of the diagnostic capabilities of
      conventional film-screen and digital angiography.
AB  - STUDY OBJECTIVE: To compare digital to conventional film-screen pulmonary
      angiography for the diagnosis of acute pulmonary embolism (PE) in a clinical
      population. DESIGN: Retrospective review of patient data, ventilation/perfusion
      (V/Q) lung scintigraphy reports, and pulmonary angiographic reports. SETTING:
      University hospital, division of interventional radiology. PATIENTS AND METHODS:
      Patient data from 307 film-screen and 266 digital angiograms were analyzed for
      demographics, V/Q lung scintigraphy findings, and pulmonary artery pressures to
      define patient populations. The interpretations of film-screen pulmonary
      angiography were then compared with digital angiography interpretations for the
      entire group of interventional radiologists as well as the two interventionists
      who practiced throughout the study interval to determine any difference in rates
      of diagnosis of acute PE between the two techniques. RESULTS: There was no
      significant difference between the patient populations studied by film-screen or
      digital techniques for the data reviewed. Digital angiography utilized
      significantly more contrast material (digital, 173 mL; film-screen, 145 mL; p <
      0.01) and a greater number of angiographic views (digital, 3.6 views per patient;
      film-screen, 3.4 views per patient; p = 0.04) when compared with film-screen
      angiography. There was no difference between the two techniques in the rates of
      diagnosis of acute PE, for individual radiologists or overall. CONCLUSIONS:
      Digital and film-screen pulmonary angiography possess equivalent diagnostic
      capabilities for acute PE as used in a clinical setting.

PMID- 12226042
TI  - Impact of morphologic characteristics of central pulmonary thromboemboli in
      massive pulmonary embolism.
AB  - STUDY OBJECTIVE: To assess the impact of morphologically different central
      pulmonary artery thromboemboli in patients with massive pulmonary emboli (MPEs)
      on short-term outcome. DESIGN: A prospective registry of consecutive patients.
      SETTING: An 11-bed closed medical ICU at a 860-bed community general hospital
      PATIENTS: Forty-seven patients with shock or hypotension due to MPE and central
      pulmonary thromboemboli detected by transesophageal echocardiography who were
      treated with thrombolysis between January 1994 and April 2000. PROCEDURES:
      Patients were divided into two groups according to the following characteristics
      of the detected thromboemboli: group 1, thrombi with one or more long, mobile
      parts; and group 2, immobile thrombi. Right heart catheterization was performed.
      RESULTS: The incidence of both types of thromboemboli was comparable. Groups 1
      and 2 showed no differences in demographic data, risk factors for pulmonary
      embolism, length of preceding clinical symptoms, percentage of patients in shock,
      hemodynamic variables, serum lactate levels on hospital admission, and treatment.
      Seven fatal cases due to obstructive shock and right heart failure were present
      in group 2, but none were present in group 1 (7 of 23 patients vs 0 of 24
      patients, respectively; p < 0.05). At 12 h, the cardiac index was lower in group
      2 than in group 1 (2.6 +/- 1.0 vs 3.1 +/- 0.9 L/min/m(2), respectively; p <
      0.05), and the central venous pressure (15.0 +/- 6.2 vs 12.5 +/- 3.7 mm Hg,
      respectively; p < 0.05) and total pulmonary resistance (12.9 +/- 5.9 vs 8.6 +/-
      2.7 mm Hg/L/min/m(2), respectively; p < 0.001) were higher in group 2 compared to
      group 1. On hospital admission, inclusion in group 2 (p < 0.03; hazard ratio,
      9.53; 95% confidence interval [CI], 1.19 to 76.47) and preexisting chronic
      medical or neurologic disease (p < 0.01; hazard ratio, 16.4; 95% CI, 1.97 to
      136.3) were independent predictors of 30-day mortality. CONCLUSION: On hospital
      admission, morphology of the thromboemboli and the presence of pre-existing
      chronic medical or neurologic disease are independent predictors of 30-day
      mortality. Patients with immobile central pulmonary thromboemboli have a worse
      short-term outcome than those with mobile central pulmonary thromboemboli.

PMID- 12226043
TI  - Automatic tube compensation-assisted respiratory rate to tidal volume ratio
      improves the prediction of weaning outcome.
AB  - OBJECTIVE: To assess whether the respiratory rate to tidal volume ratio (RVR)
      measured while receiving automatic tube compensation (ATC) [RVRATC] would have a
      better predictive value as a weaning measure than unassisted RVR. DESIGN:
      Prospective cohort study. SETTING: General ICU of a tertiary-care university
      hospital. PATIENTS: Forty-three patients who received mechanical ventilation for
      > 24 h and were considered ready for weaning. INTERVENTIONS: All patients
      underwent a 60-min spontaneous breathing trial (SBT) [positive end-expiratory
      pressure of 5 cm H(2)O; ATC, 100%]. Patients tolerating the trial (n = 35) were
      extubated immediately. The following parameters were measured at the onset and
      end of the SBT: RVR, RVRATC, peak airway pressure (Paw), airway occlusion
      pressure, and minute ventilation. The outcome measure was successful extubation
      (ability to maintain spontaneous breathing for > 48 h). MEASUREMENTS AND RESULTS:
      Median age was 55 years (range, 25 to 88 years), median APACHE (acute physiology
      and chronic health evaluation) II score was 15.5 (range, 3 to 29), and median
      duration of mechanical ventilation prior to the SBT was 7 days (range, 1 to 40
      days). Extubation was successful in 25 patients (72%). There were no significant
      differences in baseline characteristics between patients successfully extubated
      (group 1) and those requiring reintubation. On multivariate analysis, RVRATC
      measured at 60 min (RVR(60)ATC) was most predictive of successful extubation (p =
      0.03). The area under the receiver operator characteristic curve was also highest
      for RVR(60)ATC (0.81 +/- 0.03) as compared to RVR (0.77 +/- 0.03), RVRATC (0.75
      +/- 0.04), and RVR measured at 60 min (0.69 +/- 0.05). The ratio of RVR(60)ATC to
      Paw was the best predictor (0.84 +/- 0.02). CONCLUSIONS: RVRATC measured at the
      end of the SBT was the best predictor of successful extubation. A new ratio
      (ratio of RVRATC to Paw) was most predictive and deserves further study.

PMID- 12226044
TI  - Role of transbronchial needle aspiration in patients receiving mechanical
      ventilation.
AB  - STUDY OBJECTIVE: s: To evaluate the diagnostic accuracy and safety of
      transbronchial needle aspiration (TBNA) in patients receiving mechanical
      ventilation in the ICU. METHODS: Retrospective review of all patients in the
      medical and surgical ICUs from February 1999 to July 2001 who underwent TBNA
      while receiving mechanical ventilation. RESULTS: A total of eight histology (19
      gauge) and eight cytology (22 gauge) TBNAs were performed on eight patients (four
      men and four women). TBNA yielded a definitive pathologic diagnosis in five of
      eight patients (62.5%). Diagnoses were posttransplantation lymphoproliferative
      disorder, large cell carcinoma, poorly differentiated non-small cell carcinoma,
      squamous cell carcinoma, and adenocarcinoma. Among patients with negative TBNA
      results (n = 3), two patients underwent mediastinoscopy. Results of
      mediastinoscopy were non-small cell carcinoma and inflamed tissue. TBNA led to
      management changes in five of these patients. Excluding one patient in whom a
      negative TBNA result could not be further confirmed, TBNA yielded a sensitivity
      of 83%, a specificity of 100%, a positive predictive value of 100%, and a
      negative predictive value of 50%. The overall accuracy of the procedure was 75%.
      There were no complications following any of the TBNAs. CONCLUSIONS: In this
      small group of patients, TBNA was safe and had a high diagnostic accuracy in
      selected patients receiving mechanical ventilation in the ICU.

PMID- 12226045
TI  - Lack of agreement between thermodilution and fick cardiac output in critically
      ill patients.
AB  - STUDY OBJECTIVE: s: Individual comparison of cardiac output via intermittent
      thermodilution and Fick technique over a wide range of cardiac outputs. DESIGN:
      Prospective clinical investigation. SETTING: Multidisciplinary ICUs of two
      teaching hospitals in Vancouver, British Columbia. PARTICIPANTS: Eighteen
      critically ill patients who had pulmonary and systemic arterial catheters and in
      whom active support was being withdrawn. INTERVENTIONS: Measurement of
      thermodilution cardiac output and calculation of Fick cardiac output while
      support was withdrawn. Active support was withdrawn in a three-step process:
      removal of vasopressors followed by decrease in fraction of inspired oxygen to
      0.21, and finally removal of mechanical ventilation. MEASUREMENTS AND RESULTS:
      Simultaneous Fick and thermodilution cardiac outputs were obtained over a wide
      range. Fick calculated cardiac outputs were obtained using the Fick equation with
      oxygen uptake (O(2)) being measured with indirect calorimetry. O(2)
      determinations were made using five measurements over 5 min, with the mean being
      used for subsequent analysis. Thermodilution cardiac outputs were determined by
      the mean of five measurements, with the first being discarded. Coefficient of
      variation was calculated for the O(2) and thermodilution cardiac outputs. One
      hundred thirty-six simultaneous cardiac outputs were obtained in 18 patients with
      a mean APACHE (acute physiology and chronic health evaluation) II score of 25.5.
      The range of cardiac outputs was 1.39 to 16.95 L/min. Linear regression analysis
      found a good correlation of the data sets, with an R of 0.85. Bias and precision
      calculations found a bias of - 0.17 L/min with the upper and lower limits of
      agreement being 2.96 L/min and - 3.30 L/min, respectively. In patients with high
      cardiac outputs (> 7 L/min), the bias was - 1.90 with the limits of agreement
      being 1.87 L/min and - 5.67 L/min. The coefficient of variation for O(2) was 4.6%
      and for thermodilution cardiac output was 7.75%. CONCLUSIONS: There was good
      consistency of each of the measurements with a low coefficient of variation. The
      bias for the whole group was small, but the limits of agreement extended into a
      clinically relevant area, resulting in a lack of agreement. In patients with high
      cardiac outputs, the Fick tended to consistently produce higher cardiac outputs
      compared to thermodilution, suggesting a systematic error.

PMID- 12226046
TI  - Effects of positive end-expiratory pressure and body position on pulmonary blood
      flow redistribution in mechanically ventilated normal pigs.
AB  - STUDY OBJECTIVES: To assess the respective effects of position and positive end
      expiratory pressure (PEEP) on the distribution of regional pulmonary blood flow
      (PBF). DESIGN: Prospective randomized animal study. SETTING: Animal research
      facility in a university hospital. PARTICIPANTS: Normal pigs that were
      tracheostomized, anesthetized, and mechanically ventilated. INTERVENTIONS: PBF
      was measured in seven pigs in the supine position (SP) and the prone position
      (PP) at both zero end-expiratory pressure (ZEEP) and 10 cm H(2)O of PEEP. The
      regional PBF was assessed by the radioactive microsphere method. The lungs from
      each pig were sliced into 90 samples. The heterogeneity of PBF was estimated from
      its coefficient of variation. MEASUREMENTS AND RESULTS: The lung samples had a
      mean (+/- SD) weight of 1.60 +/- 0.39 g. Changing position from SP to PP at ZEEP
      redistributed PBF toward the anterior, superior, and peripheral regions and did
      not significantly reduce the coefficient of variation for regional PBF
      (reduction, 44.7 +/- 7% to 42.2 +/- 8%). Changing from the SP to PP position at
      PEEP induced a similar, but more marked, redistribution of PBF and a significant
      reduction in the coefficient of variation from 53 +/- 13% to 30.4 +/- 7% (p <
      0.001). In the SP, PEEP redistributed PBF toward the posterior, inferior, and
      central regions without changing the heterogeneity of PBF. In the PP, PEEP had
      little effect on the PBF redistribution but significantly reduced the coefficient
      of variation of PBF from 42.2 +/- 8% to 30.4 +/- 7% (p < 0.05). CONCLUSIONS: Pigs
      in the PP had altered gravitational dependence of PBF compared to that observed
      when pigs were in the SP. This effect was enhanced by using a PEEP of 10 cm
      H(2)O.

PMID- 12226047
TI  - Evolution of the stone heart after prolonged cardiac arrest.
AB  - OBJECTIVES: We hypothesized that progressive impairment in diastolic function
      during cardiopulmonary resuscitation (CPR) precedes evolution of the "stone
      heart" after failure of CPR. We therefore measured sequential changes in left
      ventricular (LV) volumes and free-wall thickness of the heart during CPR in an
      experimental model. DESIGN: Prospective, observational animal study. SETTING:
      Medical research laboratory in an university-affiliated research and educational
      institute. SUBJECTS: Domestic pigs. METHODS: Ventricular fibrillation (VF) was
      induced in 40 anesthetized male domestic pigs weighing between 38 kg and 43 kg.
      After 4 min, 7 min, or 10 min of untreated VF, electrical defibrillation was
      attempted. Failing to reverse VF in each instance, precordial compression at a
      rate of 80/min was begun coincident with mechanical ventilation. Coronary
      perfusion pressures (CPPs) were computed from the differences in time-coincident
      diastolic aortic and right atrial pressures. Left ventricular (LV) systolic and
      diastolic ventricular volumes and thickness of the LV free wall were estimated
      with transesophageal echocardiography. The stroke volumes (SVs) were computed
      from the differences in decompression diastolic and compression systolic volumes.
      Free-wall thickness was measured on the hearts at autopsy. RESULTS: Significantly
      greater CPPs were generated with the 4 min of untreated cardiac arrest.
      Progressive reductions in LV diastolic and SV and increases in LV free-wall
      thickness were documented with increasing duration of untreated VF. A stone heart
      was confirmed at autopsy in each animal that failed resuscitative efforts.
      Correlations with indicator dilution method and physical measurements at autopsy
      corresponded closely with the echocardiographic measurements. CONCLUSION:
      Progressive impairment in diastolic function terminates in a stone heart after
      prolonged intervals of cardiac arrest.

PMID- 12226048
TI  - Effects of chronic episodic hypoxia on rat upper airway muscle contractile
      properties and fiber-type distribution.
AB  - OBJECTIVE: Contraction of upper airway (UA) muscles such as the geniohyoids and
      sternohyoids dilates and/or stabilizes the UA, thereby maintaining its patency.
      Obstructive sleep apnea (OSA) is caused by episodes of UA collapse, and this
      results in chronic episodic hypoxia. Chronic continuous hypoxia affects skeletal
      muscle structure and function, but the effects of chronic episodic hypoxia on UA
      muscle structure and function are unknown. DESIGN: Rats were exposed to
      alternating periods of hypoxia and normoxia twice per minute for 8 h/d for 5
      weeks in order to mimic the intermittent hypoxia of OSA in humans. Isometric
      contractile properties were determined using strips of isolated geniohyoid and
      sternohyoid muscles in physiologic saline solution at 30 degrees C. Fiber-type
      distribution was determined using adenosine triphosphatase staining. RESULTS:
      Chronic episodic hypoxia had no significant effect on twitch or tetanic tension,
      twitch/tetanic tension ratio, contractile kinetics, tension-frequency
      relationship, or fiber-type distribution for either the sternohyoid or geniohyoid
      muscle. However, chronic episodic hypoxia did significantly increase sternohyoid
      and geniohyoid fatigue and reduced recovery from fatigue. CONCLUSIONS: Chronic
      episodic hypoxia increases UA muscle fatigue, an effect that may compromise the
      maintenance of UA patency.

PMID- 12226049
TI  - Influence of particle size on extrapleural talc dissemination after talc slurry
      pleurodesis.
AB  - BACKGROUND: Cases of acute respiratory failure reported after talc pleurodesis
      have raised concerns about its safety. It has been speculated that this pulmonary
      inflammatory syndrome is secondary to the extrapleural dissemination of the talc
      particles. STUDY OBJECTIVES: To test the hypothesis that particle size influences
      extrapleural talc deposition and pleural inflammation after talc slurry
      pleurodesis. DESIGN: Thirty rabbits underwent pleurodesis as follows: 10 rabbits
      received 200 mg/kg of the talc used for human pleurodesis, normal talc (NT); 10
      rabbits received 200 mg/kg of talc with particles of larger size, large talc
      (LT); and 10 rabbits received saline solution. Samples from the ipsilateral lung,
      chest wall, diaphragm, mediastinal pleura, heart, liver, spleen, and right kidney
      were obtained at 24 h and 7 days and processed for optic and electron microscopy
      and energy-dispersive x-ray analysis. RESULTS: Visceral pleural thickening was
      greater with NT than with LT, but no differences were observed in the macroscopic
      score of adhesions. There was more talc in the lungs of the rabbits that received
      NT than in those that received LT. Talc particles were detected in mediastinum
      (100%) and pericardium (20%), irrespective of the talc used. Three animals, all
      receiving NT, had talc particles in the liver. CONCLUSIONS: Our study shows that
      while both talcs were equally effective in achieving pleurodesis, the
      intrapleural injection of NT elicits greater pulmonary and systemic talc particle
      deposition than LT. Moreover, pleural inflammation was greater with NT than with
      LT.

PMID- 12226050
TI  - Caring for the dying patient with lung cancer.

PMID- 12226051
TI  - Prognostic factors in non-small cell lung cancer: a decade of progress.
AB  - STUDY OBJECTIVES: To provide a systematic overview of the literature
      investigating patient and tumor factors that are predictive of survival for
      patients with non-small cell lung cancer (NSCLC), and to analyze patterns in the
      design of these studies in order to highlight problematic aspects of their design
      and to advocate for appropriate directions of future studies. DESIGN: A
      systematic search of the MEDLINE database and a synthesis of the identified
      literature. MEASUREMENTS AND RESULTS: The database search (January 1990 to July
      2001) was carried out combining the MeSH terms prognosis and carcinoma, nonsmall
      cell lung. Eight hundred eighty-seven articles met the search criteria. These
      studies identified 169 prognostic factors relating either to the tumor or the
      host. One hundred seventy-six studies reported multivariate analyses. Concerning
      153 studies reporting a multivariate analysis of prognostic factors in patients
      with early-stage NSCLC, the median number of patients enrolled per study was 120
      (range, 31 to 1,281 patients). The median number of factors reported to be
      significant in univariate analyses was 4 (range, 2 to 14 factors). The median
      number of factors reported to be significant in multivariate analyses per study
      was 2 (range, 0 to 6 factors). The median number of studies examining each
      prognostic factor was 1 (range, 1 to 105 studies). Only 6% of studies addressed
      clinical outcomes other than patient survival. CONCLUSIONS: While the breadth of
      prognostic factors studied in the literature is extensive, the scope of factors
      evaluated in individual studies is inappropriately narrow. Individual studies are
      typically statistically underpowered and are remarkably heterogeneous with regard
      to their conclusions. Larger studies with clinically relevant modeling are
      required to address the usefulness of newly available prognostic factors in
      defining the management of patients with NSCLC.

PMID- 12226052
TI  - The origins of a concept: the protease-antiprotease imbalance hypothesis.

PMID- 12226053
TI  - Catastrophic cardiovascular adverse reactions to protamine are nitric
      oxide/cyclic guanosine monophosphate dependent and endothelium mediated: should
      methylene blue be the treatment of choice?
AB  - Clinical and experimental observations prove that heparin-neutralizing doses of
      protamine increase pulmonary artery pressures and decrease systemic BP. Protamine
      also increases myocardial oxygen consumption, cardiac output, and heart rate, and
      decreases systemic vascular resistance. These cardiovascular effects have
      clinical consequences that have justified studies in this area. Protamine adverse
      reactions usually have three different categories: systemic hypotension,
      anaphylactoid reactions, and catastrophic pulmonary vasoconstriction. The precise
      mechanism that explains protamine-mediated systemic hypotension is unknown. Four
      experimental protocols performed at Mayo Clinic, Rochester, MN, studied the
      intrinsic mechanism of protamine vasodilation. The first study reported in vitro
      systemic and coronary vasodilation after protamine infusion. The second in vitro
      study suggested that the pulmonary circulation is extensively involved in the
      protamine-mediated effects on endothelial function. The third study, carried out
      in anesthetized dogs, reported the methylene blue and nitric oxide synthase
      blockers neutralization of the protamine vasodilatatory effects. The fourth study
      suggested that protamine also causes endothelium-dependent vasodilation in heart
      microvessels and conductance arteries by different mechanisms including
      hyperpolarization. Reviewing these experimental results and our clinical
      experience, we suggest methylene blue as a novel approach to prevent and treat
      hemodynamic complications caused by the use of protamine after cardiopulmonary
      bypass. In the absence of prospective clinical trials, a growing body of
      cumulative clinical evidence suggests that methylene blue may be strongly
      considered as a therapeutic approach in the treatment of distributive shock.

PMID- 12226054
TI  - The inadvisability of thoracoscopic lung biopsy on patients with pulmonary
      hypertension.
AB  - The use of video-assisted thoracoscopic surgery (VATS) sometimes leads to
      additional and unnecessary risks compared with thoracotomy. We report a troubling
      case of VATS lung biopsy in a 43-year-old woman with mild pulmonary hypertension.
      A progressive elevation of pulmonary artery pressure (PAP) was noted after the
      commencement of right unilateral ventilation. When the systolic PAP reached 90 mm
      Hg (390 min after induction of anesthesia), a massive blood discharge through the
      chest drain occurred. At repeat thoracotomy, continuous blood spouting was seen
      from > 10 of the surgical sites. It was supposed that the endoscopic staplers
      were unable to maintain hemostasis with such a high PAP.

PMID- 12226055
TI  - Rigid bronchoscopy and stenting for esophageal cancer causing airway obstruction.
AB  - BACKGROUND: Thirty percent of patients with esophageal cancer have malignant
      involvement of the major airways, leading to respiratory distress and life
      threatening major airway obstruction. Tracheobronchial stenting has been reported
      to be effective in providing sustained relief from obstruction. METHODS: We
      conducted a chart review of all patients with advanced inoperable esophageal
      cancer who had malignant tracheobronchial obstruction requiring rigid
      bronchoscopy and airway stenting at our institution between June 1998 and July
      2001. Outcome measures, which included survival, efficacy, and complications,
      were recorded. RESULTS: There were 11 patients (4 women) with a mean age of 61
      years. Five patients had distant metastases at the time they underwent rigid
      bronchoscopy. Four patients who required mechanical ventilation for respiratory
      failure were successfully weaned off mechanical ventilation after the stenting
      procedure. All patients with dyspnea had immediate relief of respiratory
      symptoms, which was sustained for seven patients (64%). The mean duration of
      survival was 61 days. Two patients required repeat procedures, one for stent
      dislodgment on extubation and the other for stent migration. CONCLUSION: Stenting
      in patients with malignant tracheobronchial obstructions due to advanced
      esophageal cancer achieves immediate, dramatic, and sustainable relief in
      respiratory symptoms, conferring a survival benefit in patients whose conditions
      are otherwise deemed to be terminal.

PMID- 12226056
TI  - An unresponsive biochemistry professor in the bathtub.

PMID- 12226057
TI  - An unusual nosocomial pneumonia.

PMID- 12226058
TI  - Workplace-related chronic cough on a mushroom farm.
AB  - BACKGROUND: Mushroom spores have frequently been associated with respiratory
      allergy. The aims of this study were to elucidate the incidence and causes of
      chronic cough in a mushroom farm. METHODS: Participants were 69 mushroom workers
      who produce Hypsizigus marmoreus (Bunashimeji) and 35 control subjects. We
      excluded six workers because they had had asthma or allergic rhinitis before
      working. Participants completed a cross-sectional health survey 2 years after
      starting work at the mushroom farm. RESULTS: The mean airborne endotoxin levels
      in the harvesting and packing rooms were approximately 60-fold higher than those
      in the offices. Of 63 workers, 42 workers (67%) reported chronic cough after
      working on this farm, 19 workers had no cough, while 2 workers had
      hypersensitivity pneumonitis develop to the spore, which has been previously
      reported by us. Of the 42 workers with cough, 6 workers had organic dust toxic
      syndrome (ODTS), 18 workers had postnasal drip syndrome, 15 workers had cough
      variant asthma, and 3 workers had eosinophilic bronchitis. Seventy-one percent of
      the workers noticed the cough in the first 3 months, and the mean latent period
      in ODTS workers was the shortest. The cough had a trend to improve or disappear
      after weekend holidays. Bronchial hyperresponsiveness but not FEV(1)/FVC% in the
      42 workers with cough was significantly (p < 0.001) increased as compared with
      the control subjects. CONCLUSIONS: Working on a mushroom farm carries a
      significant risk for chronic cough from inhalation of mushroom spores, and we
      suggest that elevated airborne endotoxin on this farm is the cause.

PMID- 12226059
TI  - Passive smoking exposure: a risk factor for chronic bronchitis and asthma in
      adults?
AB  - OBJECTIVE: The effects of passive smoke exposure on respiratory health are still
      under debate. Therefore, we examined the risk of respiratory symptoms related to
      passive smoke exposure among German adults within the European Community
      Respiratory Health Survey. METHODS: The questionnaire data of the population
      based sample (n = 1,890) were analyzed. Multiple logistic regression models were
      carried out for current asthma (asthma symptoms or medication), chronic
      bronchitis (cough with phlegm for > or = 3 months per year), and wheezing as
      dependent variables, and self-reported exposure to passive smoke at home and at
      the workplace as independent variables after adjusting for city, age, gender,
      active smoking, and socioeconomic status as well as occupational exposure to
      dusts and/or gases. RESULTS: The relative odds for chronic bronchitis were
      significantly higher in subjects reporting involuntary tobacco smoke exposure in
      the workplace (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.16 to
      3.11). Likewise, the adjusted OR for asthma was slightly elevated (OR, 1.51; 95%
      CI, 0.99 to 2.32). The risk of chronic bronchitis (OR, 3.07; 95% CI, 1.56 to
      6.06), asthma (OR, 2.06; 95% CI, 1.07 to 3.97), and wheezing (OR, 2.12; 95% CI,
      1.25 to 3.58) increased significantly with a daily exposure of > 8 h. CONCLUSION:
      The control of passive smoke exposure in the workplace might reduce the risk of
      respiratory symptoms independently of exposure to other airborne contaminants.

PMID- 12226060
TI  - Endoscopic ultrasound/fine-needle aspiration diagnosis of a malignant subcarinal
      lymph node in a patient with lung cancer and a negative positron emission
      tomography scan.
AB  - Transesophageal, endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA)
      and positron emission tomography (PET) scanning are new modalities for staging
      non-small cell lung cancer (NSCLC), the roles of which are still being defined. A
      78-year-old man with a right lower lobe (RLL) mass and mediastinal adenopathy
      seen on CT scan had a PET scan that revealed only a RLL hypermetabolic area.
      EUS/FNA cytology of a subcarinal lymph node (LN) revealed the presence of NSCLC.
      This is a case of a false-negative PET scan for nodal involvement in NSCLC that
      was diagnosed with EUS/FNA. Patients with NSCLC and suspicious lymphadenopathy
      may benefit from EUS/FNA of enlarged posterior mediastinal LNs, even with
      negative findings of PET scanning.

PMID- 12226061
TI  - Clinical response of rheumatoid arthritis-associated pulmonary fibrosis to tumor
      necrosis factor-alpha inhibition.
AB  - Treatment options for patients with pulmonary fibrosis associated with rheumatoid
      disease are limited. We report a case of a 71-year-old man with a 3-year history
      of seropositive rheumatoid arthritis (RA) referred to the pulmonary clinic
      because of progressive pulmonary symptoms associated with radiographic fibrosis
      that was progressive in spite of corticosteroid treatment. In an attempt to
      control his articular symptoms and alter the course of his pulmonary fibrosis,
      treatment with IV infusion of the tumor necrosis factor (TNF)-alpha inhibitor
      infliximab was initiated. Following 1 year of therapy with this agent, the
      patient reported sustained improvement in dyspnea, cough, and exercise tolerance,
      in addition to improvement in joint symptoms. Stabilization of pulmonary function
      was indicated by repeat pulmonary function test findings. This report suggests
      that inhibition of TNF-alpha may be of significant benefit to patients with
      fibrosing lung conditions in the setting of RA.

PMID- 12226062
TI  - Effects of continuous IV prostacyclin in a patient with pulmonary veno-occlusive
      disease.
AB  - Pulmonary veno-occlusive disease (PVOD) is a rare but life-threatening disease.
      Although prostacyclin (PGI(2)) attenuates pulmonary hypertension and improves the
      prognosis in patients with primary pulmonary hypertension, little information is
      available regarding the effect of PGI(2) on patients with PVOD. This report
      describes a patient with severe PVOD who showed marked improvement in exercise
      capacity and pulmonary hemodynamics with continuous IV PGI(2) treatment.
      Furthermore, he experienced no clinical events for 12 months and survived for 25
      months after the initiation of PGI(2) therapy. These results suggest that
      continuous IV PGI(2) therapy may serve as a bridge to transplantation in some
      cases of PVOD.

PMID- 12226063
TI  - Myocardial infarction in the very young.

PMID- 12226064
TI  - Diurnal hypercapnia in patients with obstructive sleep apnea syndrome.

PMID- 12226065
TI  - Fluoroquinolones for respiratory infection: too valuable to overuse (and too
      valuable to misuse!).

PMID- 12226066
TI  - Adrenal suppression related to inhaled corticosteroids revisited.

PMID- 12226067
TI  - Altered Swallowing Physiology and Aspiration in COPD.

PMID- 12226068
TI  - Complete interatrial block revisited.

PMID- 12226069
TI  - Mediastinal hematoma following transbronchial needle aspiration.

PMID- 12226070
TI  - Medical literature implies continuous positive airway pressure might be
      appropriate treatment for irritable bowel syndrome.

PMID- 12226073
TI  - The MCM3 acetylase MCM3AP inhibits initiation, but not elongation, of DNA
      replication via interaction with MCM3.
AB  - Minichromosome maintenance (MCM) proteins are essential components of pre
      replication complexes, which limit DNA replication to once per cell cycle. MCM3
      acetylating protein, MCM3AP, binds and acetylates MCM3 and inhibits cell cycle
      progression. In the present study, we examined inhibition of the cell cycle by
      MCM3AP in a cell-free system. We show here that wild type MCM3AP, but not the
      acetylase-deficient mutant, inhibits initiation of DNA replication, but not
      elongation. Both wild type and acetylase-deficient mutant MCM3AP, however, can
      bind to chromatin through interaction with MCM3. These results indicate that MCM3
      acetylase activity of MCM3AP is required to inhibit initiation of DNA replication
      and that association of MCM3AP to chromatin alone is not sufficient for the
      inhibition. We also show that interaction between MCM3 and MCM3AP is essential
      for nuclear localization and chromatin binding of MCM3AP. Furthermore, the
      chromatin binding of MCM3AP is temporally correlated with that of endogenous MCM3
      when cells were released from mitosis. Hence, MCM3AP is a potent natural
      inhibitor of the initiation of DNA replication whose action is mediated by
      interaction with MCM3.

PMID- 12226074
TI  - The "LSGGQ" motif in each nucleotide-binding domain of human P-glycoprotein is
      adjacent to the opposing walker A sequence.
AB  - The human multidrug resistance P-glycoprotein (P-gp, ABCB1), a member of the ATP
      binding cassette (ABC) family of transport proteins, actively transports many
      cytotoxic compounds out of the cell. ABC transporters have two nucleotide-binding
      domains (NBD) and two transmembrane domains. The presence of the conserved
      "signature" sequence (LSGGQ) in each NBD is a unique feature in these
      transporters. The function of the signature sequences is unknown. In this study,
      we tested whether the signature sequences ((531)LSGGQ(535) in NBD1;
      (1176)LSGGQ(1180) in NBD2) in P-gp are in close proximity to the opposing Walker
      A consensus nucleotide-binding sequences ((1070)GSSGCGKS(1077) in NBD2;
      (427)GNSGCGKS(434) in NBD1). Pairs of cysteines were introduced into a Cys-less P
      gp at the signature and "Walker A" sites and the mutant P-gps were subjected to
      oxidative cross-linking. At 4 degrees C, when thermal motion is low, P-gp mutants
      (L531C(Signature)/C1074(Walker A) and C431(Walker A)/L1176C(Signature) were cross
      linked. Cross-linking inhibited the drug-stimulated ATPase activities of these
      two mutants. Their activities were restored, however, after addition of the
      reducing agent, dithiothreitol. Vanadate trapping of nucleotide at the ATP
      binding sites prevented cross-linking of the mutants. These results indicate that
      the signature sequences are adjacent to the opposing Walker A site. They likely
      participate in forming the ATP-binding sites and are displaced upon ATP
      hydrolysis. The resulting conformational change may be the signal responsible for
      coupling ATP hydrolysis to drug transport by inducing conformational changes in
      the transmembrane segments.

PMID- 12226075
TI  - Identification of a tyrosine in the agonist binding site of the homomeric rho1
      gamma-aminobutyric acid (GABA) receptor that, when mutated, produces spontaneous
      opening.
AB  - Mutagenesis of recombinant rho1 gamma-aminobutyric acid (GABA) receptors has
      previously identified five residues in the amino terminal extracellular domain
      that play an important role in GABA binding. Here, we present evidence that the
      tyrosine at position 102 of the rho1 receptor is also associated with the agonist
      binding site. Wild-type and mutant rho1 receptors were expressed in Xenopus
      laevis oocytes and examined using the two-electrode voltage clamp. When Tyr-102
      was mutated to cysteine, serine, tryptophan, or glycine the EC(50) increased 31-,
      214-, 664-, and 8752-fold, respectively. An increase in the IC(50) was also
      observed for the competitive antagonist 3-APMPA, but not for the non-competitive
      antagonist picrotoxin. Y102C was accessible to modification by
      methanethiosulfonate, and this modification was prevented by both GABA and 3
      APMPA. An interesting characteristic of the Y102S mutant receptor was that, in
      the absence of GABA, there was an unusually high oocyte resting conductance that
      was blocked by both 3-APMPA and picrotoxin, indicating spontaneously opening GABA
      receptors. It appears that mutation of Tyr-102 perturbs the binding site and
      gates the pore. We conclude that Tyr-102 is a component of the GABA binding
      domain and speculate that Tyr-102 might be important for coupling agonist binding
      to channel opening.

PMID- 12226076
TI  - Characterization of the structure and dynamics of a near-native equilibrium
      intermediate in the unfolding pathway of an all beta-barrel protein.
AB  - The structure and dynamics of equilibrium intermediate in the unfolding pathway
      of the human acidic fibroblast growth factor (hFGF-1) are investigated using a
      variety of biophysical techniques including multidimensional NMR spectroscopy.
      Guanidinium hydrochloride (GdnHCl)-induced unfolding of hFGF-1 proceeds with the
      accumulation of a stable intermediate state. The transition from the intermediate
      state to the unfolded state(s) is cooperative without the accumulation of
      additional intermediate(s). The intermediate state induced maximally in 0.96 m
      GdnHCl is found to be obligatory in the folding/unfolding pathway of hFGF-1. Most
      of the native tertiary structure interactions are preserved in the intermediate
      state. (1)H-(15)N chemical shift perturbation data suggest that the residues in
      the C-terminal segment including those located in the beta-strands IX, X, and XI
      undergo the most discernible structural change(s) in the intermediate state in
      0.96 m GdnHCl. hFGF-1 in the intermediate state (0.96 m GdnHCl) does not bind to
      its ligand, sucrose octasulfate. Limited proteolytic digestion experiments and
      hydrogen-deuterium exchange monitored by (15)N heteronuclear single quantum
      coherence (HSQC) spectra show that the conformational flexibility of the protein
      in the intermediate state is significantly higher than in the native
      conformation. (15)N spin relaxation experiments show that many residues located
      in beta-strands IX, X, and XI exhibit conformational motions in the micro- to
      millisecond time scale. Analysis of (15)N relaxation data in conjunction with the
      amide proton exchange kinetics suggests that residues in the beta-strands II,
      VIII, and XII possibly constitute the stability core of the protein in the near
      native intermediate state.

PMID- 12226077
TI  - Phosphorylation of p85 beta PIX, a Rac/Cdc42-specific guanine nucleotide exchange
      factor, via the Ras/ERK/PAK2 pathway is required for basic fibroblast growth
      factor-induced neurite outgrowth.
AB  - Guanine nucleotide exchange factors (GEFs) have been implicated in growth factor
      induced neuronal differentiation through the activation of small GTPases.
      Although phosphorylation of these GEFs is considered an activation mechanism,
      little is known about the upstream of PAK-interacting exchange factor (PIX), a
      member of the Dbl family of GEFs. We report here that phosphorylation of p85
      betaPIX/Cool/p85SPR is mediated via the Ras/ERK/PAK2 pathway. To understand the
      role of p85 betaPIX in basic fibroblast growth factor (bFGF)-induced neurite
      outgrowth, we established PC12 cell lines that overexpress the fibroblast growth
      factor receptor-1 in a tetracycline-inducible manner. Treatment with bFGF induces
      the phosphorylation of p85 betaPIX, as determined by metabolic labeling and
      mobility shift upon gel electrophoresis. Interestingly, phosphorylation of p85
      betaPIX is inhibited by PD98059, a specific MEK inhibitor, suggesting the
      involvement of the ERK cascade. PAK2, a major PAK isoform in PC12 cells as well
      as a binding partner of p85 betaPIX, also functions upstream of p85 betaPIX
      phosphorylation. Surprisingly, PAK2 directly binds to ERK, and its activation is
      dependent on ERK. p85 betaPIX specifically localizes to the lamellipodia at
      neuronal growth cones in response to bFGF. A mutant form of p85 betaPIX
      (S525A/T526A), in which the major phosphorylation sites are replaced by alanine,
      shows significant defect in targeting. Moreover, expression of the mutant p85
      betaPIX efficiently blocks PC12 cell neurite outgrowth. Our study defines a novel
      signaling pathway for bFGF-induced neurite outgrowth that involves activation of
      the PAK2-p85 betaPIX complex via the ERK cascade and subsequent translocation of
      this complex.

PMID- 12226078
TI  - Transactivation of vascular endothelial growth factor (VEGF) receptor Flk-1/KDR
      is involved in sphingosine 1-phosphate-stimulated phosphorylation of Akt and
      endothelial nitric-oxide synthase (eNOS).
AB  - Sphingosine 1-phosphate (S1P) and vascular endothelial growth factor (VEGF)
      elicit numerous biological responses including cell survival, growth, migration,
      and differentiation in endothelial cells mediated by the endothelial
      differentiation gene, a family of G-protein-coupled receptors, and fetal liver
      kinase-1/kinase-insert domain-containing receptor (Flk-1/KDR), one of VEGF
      receptors, respectively. Recently, it was reported that S1P or VEGF treatment of
      endothelial cells leads to phosphorylation at Ser-1179 in bovine endothelial
      nitric oxide synthase (eNOS), and this phosphorylation is critical for eNOS
      activation. S1P stimulation of eNOS phosphorylation was shown to involve G(i)
      protein, phosphoinositide 3-kinase, and Akt. VEGF also activates eNOS through Flk
      1/KDR, phosphoinositide 3-kinase, and Akt, which suggested that S1P and VEGF may
      share upstream signaling mediators. We now report that S1P treatment of bovine
      aortic endothelial cells acutely increases the tyrosine phosphorylation of Flk
      1/KDR, similar to VEGF treatment. S1P-mediated phosphorylation of Flk-1/KDR, Akt,
      and eNOS were all inhibited by VEGF receptor tyrosine kinase inhibitors and by
      antisense Flk-1/KDR oligonucleotides. Our study suggests that S1P activation of
      eNOS involves G(i), calcium, and Src family kinase-dependent transactivation of
      Flk-1/KDR. These data are the first to establish a critical role of Flk-1/KDR in
      S1P-stimulated eNOS phosphorylation and activation.

PMID- 12226079
TI  - Nitric oxide-dependent processing of heparan sulfate in recycling S-nitrosylated
      glypican-1 takes place in caveolin-1-containing endosomes.
AB  - We have previously demonstrated intracellular degradation of the heparan sulfate
      side chains in recycling glypican-1 by heparanase and by deaminative cleavage at
      N-unsubstituted glucosamine with nitric oxide derived from intrinsic
      nitrosothiols (see Ding, K., Mani, K., Cheng, F., Belting, M. and Fransson, L.-A.
      (2002) J. Biol. Chem. 277, 33353-33360). To determine where and in what order
      events take place, we have visualized, by using confocal laser-scanning
      immunofluorescence microscopy, glypican-1 variants in unperturbed cells or
      arrested at various stages of processing. In unperturbed proliferating cells,
      glypican-1 was partly S-nitrosylated. Intracellular glypican-1 was enriched in
      endosomes, colocalized significantly with GM-1 ganglioside, caveolin-1, and Rab9
      positive endosomes, and carried side chains rich in N-unsubstituted glucosamine
      residues. However, such residues were scarce in cell surface glypican-1.
      Brefeldin A-arrested glypican-1, which was non-S-nitrosylated and carried side
      chains rich in N-unsubstituted glucosamines, colocalized extensively with
      caveolin-1 but not with Rab9. Suramin, which inhibits heparanase, induced the
      appearance of S-nitrosylated glypican-1 in caveolin-1-rich compartments.
      Inhibition of deaminative cleavage did not prevent heparanase from generating
      heparan sulfate oligosaccharides that colocalized strongly with caveolin-1.
      Growth-quiescent cells displayed extensive NO-dependent deaminative cleavage of
      heparan sulfate-generating anhydromannose-terminating fragments that were partly
      associated with acidic vesicles. Proliferating cells generated such fragments
      during polyamine uptake. We conclude that recycling glypican-1 that is associated
      with caveolin-1-containing endosomes undergoes sequential N-desulfation/N
      deacetylation, heparanase cleavage, S-nitrosylation, NO release, and deaminative
      cleavage of its side chains in conjunction with polyamine uptake.

PMID- 12226080
TI  - Differential modulation of androgen receptor-mediated transactivation by Smad3
      and tumor suppressor Smad4.
AB  - Smad proteins have been demonstrated to be key components in the transforming
      growth factor beta signaling cascade. Here we demonstrate that Smad4, together
      with Smad3, can interact with the androgen receptor (AR) in the DNA-binding and
      ligand-binding domains, which may result in the modulation of 5alpha
      dihydrotestosterone-induced AR transactivation. Interestingly, in the prostate
      PC3 and LNCaP cells, addition of Smad3 can enhance AR transactivation, and co
      transfection of Smad3 and Smad4 can then repress AR transactivation in various
      androgen response element-promoter reporter assays as well as Northern blot and
      reverse transcription-PCR quantitation assays with prostate-specific antigen mRNA
      expression. In contrast, in the SW480.C7 cells, lacking endogenous functional
      Smad4, the influence of Smad3 on AR transactivation is dependent on the various
      androgen response element-promoters. The influence of Smad3/Smad4 on the AR
      transactivation may involve the acetylation since the treatment of trichostatin A
      or sodium butyrate can reverse Smad3/Smad4-repressed AR transactivation and
      Smad3/Smad4 complex can also decrease the acetylation level of AR. Together,
      these results suggest that the interactions between AR, Smad3, and Smad4 may
      result in the differential regulation of the AR transactivation, which further
      strengthens their roles in the prostate cancer progression.

PMID- 12226081
TI  - Functional cross-talk among Rad51, Rad54, and replication protein A in
      heteroduplex DNA joint formation.
AB  - Saccharomyces cerevisiae Rad51, Rad54, and replication protein A (RPA) proteins
      work in concert to make heteroduplex DNA joints during homologous recombination.
      With plasmid length DNA substrates, maximal DNA joint formation is observed with
      amounts of Rad51 substantially below what is needed to saturate the initiating
      single-stranded DNA template, and, relative to Rad51, Rad54 is needed in only
      catalytic quantities. RPA is still indispensable for optimal reaction efficiency,
      but its role in this instance is to sequester free single-stranded DNA, which
      otherwise inhibits Rad51 and Rad54 functions. We also demonstrate that Rad54
      helps overcome various reaction constraints in DNA joint formation. These results
      thus shed light on the function of Rad54 in the Rad51-mediated homologous DNA
      pairing reaction and also reveal a novel role of RPA in the presynaptic stage of
      this reaction.

PMID- 12226082
TI  - NF-kappa B activation mediates the cross-talk between extracellular matrix and
      interferon-gamma (IFN-gamma) leading to enhanced monokine induced by IFN-gamma
      (MIG) expression in macrophages.
AB  - In intact tissue, the extracellular matrix (ECM) provides support and helps
      maintain homeostasis but is considered biologically inert. In the setting of
      inflammation, not only is the ECM the target of inflammation, but its breakdown
      products modulate the magnitude and quality of an immune response. Fragments of
      the ECM component hyaluronan (HA) induce macrophage expression of chemokines,
      cytokines, and growth factors as well greatly enhance IFN-gamma-induced MIG
      expression. In this report, we demonstrate that the synergistic induction of MIG
      by HA and IFN-gamma occurs at the level of transcription via NF-kappaB. Using
      electrophoretic mobility shift assays and reporter assays, we have identified two
      NF-kappaB sites proximal to the IFN-gamma-responsive element-1 (gammaRE-1) that
      mediate this effect. Interestingly, our experiments also revealed a critical role
      for NF-kappaB in mediating IFN-gamma-induced MIG expression independent of HA.
      These data emphasize the ability of "degraded self" to activate/modify immune
      responses through the NF-kappaB pathway.

PMID- 12226083
TI  - GABA(A) receptor M2-M3 loop secondary structure and changes in accessibility
      during channel gating.
AB  - The gamma-aminobutyric acid type A (GABA(A)) receptor M2-M3 loop structure and
      its role in gating were investigated using the substituted cysteine accessibility
      method. Residues from alpha(1)Arg-273 to alpha(1)Ile-289 were mutated to
      cysteine, one at a time. MTSET(+) or MTSES(-) reacted with all mutants from
      alpha(1)R273C to alpha(1)Y281C, except alpha(1)P277C, in the absence and presence
      of GABA. The MTSET(+) closed-state reaction rate was >1000 liters/mol-s at
      alpha(1)N274C, alpha(1)S275C, alpha(1)K278C, and alpha(1)Y281C and was <300
      liters/mol-s at alpha(1)R273C, alpha(1)L276C, alpha(1)V279C, alpha(1)A280C, and
      alpha(1)A284C. These two groups of residues lie on opposite sides of an alpha
      helix. The fast reacting group lies on a continuation of the M2 segment channel
      lining helix face. This suggests that the M2 segment alpha-helix extends about
      two helical turns beyond alpha(1)N274 (20'), aligned with the extracellular ring
      of charge. At alpha(1)S275C, alpha(1)V279C, alpha(1)A280C, and alpha(1)A284C the
      reaction rate was faster in the presence of GABA. The reagents had no functional
      effect on the mutants from alpha(1)A282C to alpha(1)I289C, except alpha(1)A284C.
      Access may be sterically hindered possibly by close interaction with the
      extracellular domain. We suggest that the M2 segment alpha-helix extends beyond
      the predicted extracellular end of the M2 segment and that gating induces a
      conformational change in and/or around the N-terminal half of the M2-M3 loop.
      Implications for coupling ligand-evoked conformational changes in the
      extracellular domain to channel gating in the membrane-spanning domain are
      discussed.

PMID- 12226084
TI  - The metabolic architecture of plant cells. Stability of central metabolism and
      flexibility of anabolic pathways during the growth cycle of tomato cells.
AB  - The changes in the intermediary metabolism of plant cells were quantified
      according to growth conditions at three different stages of the growth cycle of
      tomato cell suspension. Eighteen fluxes of central metabolism were calculated
      from (13)C enrichments after near steady-state labeling by a metabolic model
      similar to that described in Dieuaide-Noubhani et al. (Dieuaide-Noubhani, M.,
      Raffard, G., Canioni, P., Pradet, A., and Raymond, P. (1995) J. Biol. Chem. 270,
      13147-13159), and 10 net fluxes were obtained directly from end-product
      accumulation rates. The absolute flux values of central metabolic pathways
      gradually slowed down with the decrease of glucose influx into the cells.
      However, the relative fluxes of glycolysis, the pentose-P pathway, and the
      tricarboxylic acid cycle remained unchanged during the culture cycle at 70, 28,
      and 40% of glucose influx, respectively, and the futile cycle of sucrose remained
      high at about 6-fold the glucose influx, independently from carbon nutritional
      conditions. This natural resistance to flux alterations is referred to as
      metabolic stability. The numerous anabolic pathways, including starch synthesis,
      hexose accumulation, biosynthesis of wall polysaccharides, and amino and organic
      acid biosynthesis were comparatively low and variable. The phosphoenolpyruvate
      carboxylase flux decreased 5-fold in absolute terms and 2-fold in relation to the
      glucose influx rate during the culture cycle. We conclude that anabolic fluxes
      constitute the flexible part of plant cell metabolism that can fluctuate in
      relation to cell demands for growth.

PMID- 12226085
TI  - Interaction between two ubiquitin-protein isopeptide ligases of different
      classes, CBLC and AIP4/ITCH.
AB  - In metazoans, CBL proteins are RING finger type ubiquitin-protein isopeptide (E3)
      ligases involved in the down-regulation of epidermal growth factor tyrosine
      kinase receptors (EGFR). Among the three CBL proteins described in humans, CBLC
      (CBL3) remains poorly studied. By screening in parallel a human and a
      Caenorhabditis elegans library using the two-hybrid procedure in yeast, we found
      a novel interaction between Hsa-CBLC and Hsa-AIP4 or its C. elegans counterpart
      Cel-WWP1. Hsa-AIP4 and Cel-WWP1 are also ubiquitin E3 ligases. They contain a
      HECT (homologous to E6-AP C terminus) catalytic domain and four WW domains known
      to bind proline-rich regions. We confirmed the interaction between Hsa-CBLC and
      Hsa-AIP4 by a combination of glutathione S-transferase pull-down, co
      immunoprecipitation, and colocalization experiments. We show that these two E3
      ligases are involved in EGFR signaling because both become phosphorylated on
      tyrosine following epidermal growth factor stimulation. In addition, we observed
      that CBLC increases the ubiquitination of EGFR, and that coexpressing the WW
      domains of AIP4 exerts a dominant negative effect on EGFR ubiquitination.
      Finally, coexpressing CBLC and AIP4 induces a down-regulation of EGFR signaling.
      In conclusion, our data demonstrate that two E3 ligases of different classes can
      interact and cooperate to down-regulate EGFR signaling.

PMID- 12226086
TI  - Requirement of nuclear factor of activated T-cells in calcineurin-mediated
      cardiomyocyte hypertrophy.
AB  - The calcium-activated phosphatase calcineurin has been implicated as a critical
      intracellular signal transducer of cardiomyocyte hypertrophy. Although previous
      data suggested the nuclear factor of activated T-cells (NFAT) as its sole
      transcriptional effector, the absolute requirement of NFAT as a mediator of
      calcineurin signaling has not been examined in the heart. We therefore
      investigated the expression and activation profile of NFAT genes in the heart.
      Four members (NFATc1-c4) are expressed in cardiomyocytes, elicit nuclear
      translocation upon calcineurin activation, and are able to drive transactivation
      of cardiac promoter luciferase constructs. To define the necessary function of
      NFAT factors as hypertrophic transducers, a dominant negative NFAT construct was
      created, encompassing part of the N-terminal region of NFATc4 containing a
      conserved calcineurin-binding motif. Cotransfection of this construct dose
      dependently abrogated promoter activation, irrespective of the NFAT isoform used,
      whereas a control construct with the calcineurin-binding motif mutated displayed
      no such effects. Adenoviral gene transfer of dominant negative NFAT rendered
      cardiomyocytes resistant toward all aspects of calcineurin or agonist-induced
      cardiomyocyte hypertrophy, whereas adenoviral gene transfer of the control
      construct had no discernable effect on these parameters. These results indicate
      that multiple NFAT isoforms are expressed in cardiomyocytes where they function
      as necessary transducers of calcineurin in facilitating cardiomyocyte
      hypertrophy.

PMID- 12226087
TI  - Identification of Hsp90 as a stimulatory host factor involved in influenza virus
      RNA synthesis.
AB  - Efficient transcription and replication of the influenza virus genome are
      dependent upon host-derived factors. Using an in vitro RNA synthesis system, we
      have purified and identified Hsp90 as one of the host factors that stimulate
      viral RNA polymerase activity. Hsp90 interacted with the PB2 subunit of the viral
      RNA polymerase through the amino-terminal chaperone domain and the middle region
      containing a highly acidic domain. The acidic middle region was also responsible
      for its stimulatory activity. We found that a portion of Hsp90 is re-localized to
      the cell nucleus after viral infection. A PB2 fragment containing a Hsp90 binding
      domain inhibited viral gene expression in a dominant-negative manner. These
      results suggest that Hsp90 is a host factor for the influenza virus RNA
      polymerase.

PMID- 12226088
TI  - Binding of the concave surface of the Sds22 superhelix to the alpha 4/alpha
      5/alpha 6-triangle of protein phosphatase-1.
AB  - Functional studies of the protein phosphatase-1 (PP1) regulator Sds22 suggest
      that it is indirectly and/or directly involved in one of the most ancient
      functions of PP1, i.e. reversing phosphorylation by the Aurora-related protein
      kinases. We predict that the conserved portion of Sds22 folds into a curved
      superhelix and demonstrate that mutation to alanine of any of eight residues
      (Asp(148), Phe(170), Glu(192), Phe(214), Asp(280), Glu(300), Trp(302), or
      Tyr(327)) at the concave surface of this superhelix thwarts the interaction with
      PP1. Furthermore, we show that all mammalian isoforms of PP1 have the potential
      to bind Sds22. Interaction studies with truncated versions of PP1 and with
      chimeric proteins comprising fragments of PP1 and the yeast PP1-like protein
      phosphatase Ppz1 suggest that the site(s) required for the binding of Sds22
      reside between residues 43 and 173 of PP1gamma(1). Within this region, a major
      interaction site was mapped to a triangular region delineated by the alpha4-,
      alpha5-, and alpha6-helices. Our data also show that well known regulatory
      binding sites of PP1, such as the RVXF-binding channel, the beta12/beta13-loop,
      and the acidic groove, are not essential for the interaction with Sds22.

PMID- 12226089
TI  - Protein tyrosine phosphatases are up-regulated and participate in cell death
      induced by polyglutamine expansion.
AB  - Polyglutamine expansion is the cause of several neurodegenerative diseases. An in
      vitro model of polyglutamine-induced neuronal cell death was developed using
      truncated mutant huntingtin (Htt) and PC12 cells. Cell death was specifically
      observed in cells expressing a truncated mutant huntingtin-green fluorescence
      protein (GFP) fusion protein with 118 glutamine repeats (Gln(118)), as
      demonstrated by the release of lactate dehydrogenase (LDH). To gain further
      insights into the mechanisms of polyglutamine expansion-induced cell death, the
      Affymetrix rat genome array U34A was used to investigate gene expression changes
      associated with polyglutamine-mediated protein aggregation and cell death. Among
      the up-regulated genes, the increase of four protein tyrosine phosphatases (PTPs)
      was further confirmed by real-time quantitative reverse transcription PCR.
      Protein expression of mitogen activated protein (MAP) kinase phosphatase 1 (MKP1)
      was also increased as demonstrated by Western blot. Furthermore, phosphorylation
      of MAP kinase extracellular signal-regulated kinase 1/2 (ERK1/2) was
      substantially reduced in association with protein aggregation, and two general
      PTP inhibitors, sodium orthovanadate and bpV(pic), dramatically rescued the cells
      from polyglutamine-induced cell death. These results suggest that one or more of
      the PTPs are involved in the polyglutamine-induced cell death.

PMID- 12226090
TI  - Matrix metalloproteinase-dependent activation of latent transforming growth
      factor-beta controls the conversion of osteoblasts into osteocytes by blocking
      osteoblast apoptosis.
AB  - Upon termination of bone matrix synthesis, osteoblasts either undergo apoptosis
      or differentiate into osteocytes or bone lining cells. In this study, we
      investigated the role of matrix metalloproteinases (MMPs) and growth factors in
      the differentiation of osteoblasts into osteocytes and in osteoblast apoptosis.
      The mouse osteoblast cell line MC3T3-E1 and primary mouse calvarial osteoblasts
      were either grown on two-dimensional (2-D) collagen-coated surfaces, where they
      morphologically resemble flattened, cuboidal bone lining cells, or embedded in
      three-dimensional (3-D) collagen gels, where they resemble dendritic osteocytes
      constituting a network of cells. When MC3T3-E1 osteoblasts were grown in a 3-D
      matrix in the presence of an MMP inhibitor (GM6001), the cell number was dose
      dependently reduced by approximately 50%, whereas no effect was observed on a 2-D
      substratum. In contrast, the murine mature osteocyte cell line, MLO-Y4, was
      unaffected by GM6001 under all culture conditions. According to TUNEL assay, the
      osteoblast apoptosis was increased 2.5-fold by 10 microm GM6001. To investigate
      the mechanism by which MMPs mediate the survival of osteoblasts, we examined the
      effect of GM6001 on MC3T3-E1 osteoblasts in the presence of extracellular matrix
      components and growth factors, including tenascin, fibronectin, laminin,
      collagenase-cleaved collagen, gelatin, parathyroid hormone, basic fibroblast
      growth factor, vascular epidermal growth factor, insulin-like growth factor,
      interleukin-1, and latent and active transforming growth factor-beta (TGF-beta).
      Only active TGF-beta, but not latent TGF-beta or other agents tested, restored
      cell number and apoptosis to control levels. Furthermore, we found that the
      membrane type MMP, MT1-MMP, which is produced by osteoblasts, could activate
      latent TGF-beta and that antibodies neutralizing endogenous TGF-beta led to a
      similar decrease in cell number as GM6001. Whereas inhibitors of other protease
      families did not induce osteoblast apoptosis, an inhibitor of the p44/42 mitogen
      activated protein kinase showed the same but non-synergetic effect as GM6001.
      These findings suggest that MMP-activated TGF-beta maintains osteoblast survival
      during trans-differentiation into osteocytes by a p44/42-dependent pathway.

PMID- 12226091
TI  - The TSC1 tumor suppressor hamartin interacts with neurofilament-L and possibly
      functions as a novel integrator of the neuronal cytoskeleton.
AB  - Tuberous sclerosis complex, an autosomal dominant disease caused by mutations in
      either TSC1 or TSC2, is characterized by the development of hamartomas in a
      variety of organs. The proteins encoded by TSC1 and TSC2, hamartin and tuberin,
      respectively, associate with each other forming a tight complex. Here we show
      that hamartin binds the neurofilament light chain and it is possible to recover
      the hamartin-tuberin complex over the neurofilament light chain rod domain
      spanning amino acids 93-156 by affinity precipitation. Homologous rod domains in
      other intermediate filaments such as neurofilament medium chain, alpha
      internexin, vimentin, and desmin are not able to bind hamartin. In cultured
      cortical neurons, hamartin and tuberin co-localize with neurofilament light chain
      preferentially in the proximal to central growth cone region. Interestingly, in
      the distal part of the growth cone hamartin overlaps with the ezrin-radixin
      moesin family of actin binding proteins, and we have validated the interaction of
      hamartin with moesin. These results demonstrate that hamartin may anchor neuronal
      intermediate filaments to the actin cytoskeleton, which may be critical for some
      of the CNS functions of the hamartin-tuberin complex, and abolishing this through
      mutations in TSC1 or TSC2 may lead to certain neurological manifestations
      associated with the disease.

PMID- 12226092
TI  - Correlation of biochemical properties with the oligomeric state of human rad52
      protein.
AB  - The human Rad52 protein self-associates to form ring-shaped oligomers, as well as
      higher order complexes of these rings. We have shown previously that there are
      two experimentally separable self-association domains in HsRad52, one in the N
      terminus (residues 1-192) responsible for assembly of individual subunits into
      rings, and one in the C terminus (residues 218-418) responsible for higher order
      oligomerization of rings. Earlier studies suggest that the higher order complexes
      promote DNA end-joining, and others suggest that these complexes are relevant to
      in vivo Rad52 function. In this study we demonstrate that although inherent
      binding to single-stranded DNA depends on neither higher order complexes of Rad52
      rings nor the ring-shaped oligomers themselves, higher order complexes are
      important for activities involving simultaneous interaction with more than one
      DNA molecule. This provides biochemical support for what may be an important in
      vivo function of Rad52.

PMID- 12226093
TI  - Truncation of CDK5 activator p35 induces intensive phosphorylation of
      Ser202/Thr205 of human tau.
AB  - Hyperphosphorylated tau is a major component of neurofibrillary tangles, one of
      the hallmarks of Alzheimer's disease. CDK5 is a kinase that phosphorylates the
      tau protein, and its endogenous activator, p35, regulates its activity. Recently,
      calpain was found to digest p35 to its truncated product, p25. Several lines of
      evidence suggest that p25-CDK5 has much more powerful kinase activity and that it
      may cause abnormal hyperphosphorylation of tau. In this study, we have examined
      the kinetic characteristics of in vitro phosphorylation of the longest isoform of
      human tau by CDK5 and its activators using recombinant proteins. Although the
      kinase activity of CDK5 in phosphorylating tau was significantly higher in the
      presence of p25, the affinity of CDK5 for tau was not different. Phosphopeptide
      mapping revealed enhanced phosphorylation of Ser(202)/Thr(205) residues by p25
      CDK5 (amino acid residues of tau are numbered according to the longest isoform of
      human tau). These results suggest that cleavage of p35 to p25 greatly enhances
      the kinase activity of CDK5 and increases the phosphorylation of
      Ser(202)/Thr(205). Considering the fact that phosphorylation of Ser(202)/Thr(205)
      antagonizes the tau-mediated nucleation of tubulin, p25-CDK5 may play a pivotal
      role in neuronal cell death in Alzheimer's disease.

PMID- 12226094
TI  - Proteinase-mediated release of epithelial cell-associated CD44. Extracellular
      CD44 complexes with components of cellular matrices.
AB  - CD44 is a receptor for the matrix glycosaminoglycan hyaluronan. Proteoglycan
      forms of CD44 also exhibit affinity for fibronectin and collagen as well as
      chemokines and growth factors. CD44 plays a role in autoimmunity, inflammation,
      and tumor progression. Soluble CD44 (sCD44) is found in plasma, and the levels of
      sCD44 correlate with immune function and some malignancies. The mechanisms by
      which sCD44 is generated and its function are unknown. We demonstrate here that
      normal bronchial epithelial cells spontaneously release sCD44. Exposure to
      phagocyte- and bacterium-derived proteinases markedly increased the release of
      sCD44 from epithelial cells. The spontaneously released sCD44 was incorporated
      into high molecular mass complexes derived from the matrix that also contained
      chondroitin sulfate, fibronectin, hyaluronan, and collagens I and IV. Enzymatic
      digestion with proteinases liberated sCD44 from the high molecular mass complex.
      Consistent with the homology of CD44 to proteoglycan core and link proteins,
      these data suggest that CD44 spontaneously released from normal bronchial
      epithelial cells can accumulate as an integral component of the matrix, where it
      may play a role in the organization of matrices and in anchoring growth factors
      and chemokines to the matrix. Increases in plasma CD44 during immune activation
      and tumor progression therefore may be a manifestation of the matrix remodeling
      that occurs in the face of the enhanced proteolytic activity associated with
      infection, inflammation, and tumor metastasis, leading to alterations in cell
      matrix interactions.

PMID- 12226095
TI  - Modulation of heat-shock protein 27 (Hsp27) anti-apoptotic activity by
      methylglyoxal modification.
AB  - Methylglyoxal (MG) is one of the side-products in glycolysis, and it reacts with
      proteins under physiological conditions. Here, we identified heat-shock protein
      27 (Hsp27) as a major MG-modified protein in cells. MG modification of Hsp27
      selectively occurs at Arg-188 to form argpyrimidine, and mutation in the residue
      represses the formation of a large oligomer. This modification process is
      essential to its repressing activity for cytochrome c-mediated caspase
      activation. Inhibition of MG modification of Hsp27 causes sensitization of the
      cells to anti-tumor drug-induced apoptosis. Thus, MG is a novel modulator of cell
      survival by directly incorporating with the specific protein residue.

PMID- 12226096
TI  - Subcloning, expression, purification, and characterization of recombinant human
      leptin-binding domain.
AB  - A subdomain of the human leptin receptor encoding part of the extracellular
      domain (amino acids 428 to 635) was subcloned, expressed in a prokaryotic host,
      and purified to homogeneity, as evidenced by SDS-PAGE, with over 95% monomeric
      protein. The purified leptin-binding domain (LBD) exhibited the predicted beta
      structure, was capable of binding human, ovine, and chicken leptins, and formed a
      stable 1:1 complex with all mammalian leptins. The binding kinetics, assayed by
      surface plasmon resonance methodology, showed respective k(on) and k(off) values
      (mean +/- S.E.) of 1.20 +/- 0.23 x 10(-5) mol(-1) s(-1) and 1.85 +/- 0.30 x 10(
      3) s(-1) and a K(d) value of 1.54 x 10(-8) m. Similar results were achieved with
      conventional binding experiments. LBD blocked leptin-induced, but not interleukin
      3-induced, proliferation of BAF/3 cells stably transfected with the long form of
      human leptin receptor. The modeled LBD structure and the known three-dimensional
      structure of human leptin were used to construct a model of 1:1 LBD.human leptin
      complex. Two main residues, Phe-500, located in loop L3, and Tyr-441, located in
      L1, are suggested to contribute to leptin binding.

PMID- 12226097
TI  - Glutathione influences c-Myc-induced apoptosis in M14 human melanoma cells.
AB  - The objective of this article is to dissect the mechanisms by which the down
      regulation of c-Myc induces programmed cell death in melanoma cells. In stable
      and doxycycline-inducible M14 melanoma cells, down-regulation of c-Myc induced
      apoptosis subsequent to a decrease in the intracellular reduced glutathione
      content and a concomitant accumulation of its oxidized form. This redox
      alteration was associated with a decrease of the enzyme activities of gamma
      glutamyl-cysteine synthetase and NADPH-dependent GSSG reductase, as well as a
      consequent glutathione release in the extracellular medium. Cytochrome c was
      released into the cytosol at very early stages of apoptosis induction, long
      before detectable production of reactive oxygen species and activation of caspase
      9 and -3. Macroarray analysis revealed that down-regulation of c-Myc produced
      striking changes in gene expression in the section related to metabolism, where
      the expression of gamma-glutamyl-cysteine synthetase and GSSG reductase was found
      to be significantly reduced. The addition of N-acetyl-l-cysteine or glutathione
      ethyl ester inhibited the apoptotic process, thus confirming the key role of
      glutathione in programmed cell death induced by c-Myc.

PMID- 12226098
TI  - Osmotic shrinkage of human cervical cancer cells induces an extracellular Cl- 
      dependent nonselective cation channel, which requires p38 MAPK.
AB  - This study is to integrate a functional role of nonselective cation (NSC)
      channels into a model of volume regulation on osmotic shrinkage for human
      cervical cancer cells. Application of a hypertonic solution (400 mosm kg(-1))
      induced cell shrinkage, which was accompanied by a 7-fold increase of inward
      currents at -80 mV from -4.1 +/- 0.4 pA pF(-1) to -29 +/- 1.1 pA pF(-1) (n = 36,
      p < 0.001). There is a good correlation of channel activity and cell volume
      changes. Replacement of bath Na(+) by K(+), Cs(+), Li(+), or Rb(+) did not affect
      the stimulated inward current significantly, but replacement by Ca(2+), Ba(2+),
      or the impermeable cation N-methyl-d-glucamine abolished the inward current; this
      demonstrates that the shrinkage-induced currents discriminate poorly between
      monovalent cations but are not carried by divalent cations. Replacement of
      extracellular Cl(-) by gluconate abolished the shrinkage-induced currents in a
      concentration-dependent manner without changing the reversal potential.
      Gadolinium (Gd(3+)) inhibited the stimulated current, whereas bumetanide and
      amiloride had no inhibitory effect. Cell shrinkage triggered mitogen-activated
      protein (MAP) kinase cascades leading to the activation of MAP/extracellular
      signal-regulated kinase 1/2 (ERK1/2) kinase (MEK1/2), and p38 kinase.
      Interference with p38 MAPK by either the specific inhibitor (SB202190), or a
      dominant-negative mutant profoundly suppressed the activation of the shrinkage
      induced NSC channels. In contrast, the regulatory mechanism of shrinkage-induced
      NSC channels was independent of the volume-responsive MEK1/2 signaling pathway.
      More importantly, the cell volume response to hypertonicity was inhibited
      significantly in p38 dominant-negative mutant or by SB202190. Therefore, p38 MAPK
      is critically involved in the activation of a shrinkage-induced NSC channel,
      which plays an important role in the volume regulation of human cervical cancer
      cells.

PMID- 12226099
TI  - DNA interstrand cross-links of the novel antitumor trinuclear platinum complex
      BBR3464. Conformation, recognition by high mobility group domain proteins, and
      nucleotide excision repair.
AB  - The novel phase II antitumor polynuclear platinum drug BBR3464 ([(trans
      PtCl(NH(3))(2))(2)(mu-trans-Pt(NH(3))(2)(NH(2)(CH(2))(6)NH(2))(2))](NO(3))(4))
      forms intra- and interstrand cross-links (CLs) on DNA (which is the
      pharmacological target of platinum drugs). We examined first in our recent work
      how various intrastrand CLs of BBR3464 affect the conformation of DNA and its
      recognition by cellular components (Zehnulova, J., Kasparkova, J., Farrell, N.,
      and Brabec, V. (2001) J. Biol. Chem. 276, 22191-22199). In the present work, we
      have extended the studies on the DNA interstrand CLs of this drug. The results
      have revealed that the interstrand CLs are preferentially formed between guanine
      residues separated by 2 base pairs in both the 3' --> 3' and 5' --> 5'
      directions. The major 1,4-interstrand CLs distort DNA, inducing a directional
      bending of the helix axis and local unwinding of the duplex. Although such
      distortions represent a potential structural motif for recognition by high
      mobility group proteins, these proteins do not recognize 1,4-interstrand CLs of
      BBR3464. On the other hand, in contrast to intrastrand adducts of BBR3464, 1,4
      interstrand CLs are not removed from DNA by nucleotide excision repair. It has
      been suggested that interstrand CLs of BBR3464 could persist considerably longer
      in cells compared with intrastrand adducts, which would potentiate the toxicity
      of the interstrand lesions to tumors sensitive to this polynuclear drug.

PMID- 12226100
TI  - Saccharomyces cerevisiae RAD5 influences the excision repair of DNA minor groove
      adducts.
AB  - Nucleotide excision repair (NER) is the primary pathway for the removal of DNA
      adducts that distort the double helix. In the yeast Saccharomyces cerevisiae the
      RAD6 epistasis group defines a more poorly characterized set of DNA damage
      response pathways, believed to be distinct from NER. Here we show that the
      elimination of the DNA minor groove adducts formed by an important class of
      anticancer antibiotic (CC-1065 family) requires NER factors in S. cerevisiae. We
      also demonstrate that the elimination of this class of minor groove adduct from
      the active MFA2 gene depends upon functional Rad18 and Rad6. This is most clear
      for the repair of adducts on the transcribed strand, where an absolute
      requirement for Rad6 and Rad18 was seen. Further experiments revealed that a
      specific RAD6-RAD18-controlled subpathway, the RAD5 branch, mediates these
      events. Cells disrupted for rad5 are highly sensitive to this minor groove
      binding agent, and rad5 cells exhibit an in vivo adduct elimination defect
      indistinguishable from that seen in rad6 and rad18 cells as well as in NER
      defective cells. Our results indicate that the RAD5 subpathway may interact with
      NER factors during the repair of certain DNA adducts.

PMID- 12226101
TI  - Expression of calcineurin B homologous protein 2 protects serum deprivation
      induced cell death by serum-independent activation of Na+/H+ exchanger.
AB  - The calcineurin B homologous protein (designated CHP1) has been shown to be a
      common essential cofactor for the plasma membrane Na(+)/H(+) exchangers (NHEs)
      (Pang, T., Su, X., Wakabayashi, S., and Shigekawa, M. (2001) J. Biol. Chem. 276,
      17367-17372). In this study, we characterized the function of another isoform of
      CHP (designated CHP2) that has a 61% amino acid identity with CHP1. CHP2, like
      CHP1, conferred the ability to NHEs 1-3 to express a high exchange activity by
      binding to the juxtamembrane region of the cytoplasmic domain of the exchanger,
      but it interacts more strongly (approximately 5-fold) with NHE1 than does CHP1.
      Although CHP1 is expressed ubiquitously at relatively high levels, CHP2
      expression was extremely low in most human tissues but was higher in tumor cells.
      We produced stable cell clones overexpressing either CHP1 or CHP2 in which one of
      them is predominantly bound to NHE1. Serum (10%) induced a significant
      cytoplasmic alkalinization (0.1-0.2 pH unit) in cells co-expressing CHP1 and NHE1
      but not in cells co-expressing CHP2 and NHE1. In the latter, pH(i) was high (7.4
      7.5) even in the absence of serum, suggesting that NHE1 was already activated.
      Surprisingly, most (>80%) of CHP2/NHE1 cells unlike CHP1/NHE1 cells were viable
      even after long serum starvation (>7 days). Thus, the expression of CHP2 appears
      to protect cells from serum deprivation-induced death by increasing pH(i). These
      properties of CHP2/NHE1 cells are similar to those of malignantly transformed
      cells. We propose that serum-independent activation of NHE1 by bound CHP2 is one
      of the key mechanisms for the maintenance of high pH(i) and the resistance to
      serum deprivation-induced cell death in malignantly transformed cells.

PMID- 12226104
TI  - Kinetic analysis of the translocation of fluorescent precursor proteins into
      Escherichia coli membrane vesicles.
AB  - Protein secretion in Escherichia coli is mediated by translocase, a multi-subunit
      membrane protein complex with SecA as ATP-driven motor protein and the SecYEG
      complex as translocation pore. A fluorescent assay was developed to facilitate
      kinetic studies of protein translocation. Single cysteine mutants of proOmpA were
      site-specific labeled with fluorescent dyes, and the SecA and ATP-dependent
      translocation into inner membrane vesicles and SecYEG proteoliposomes was
      monitored by means of protease accessibility and in gel fluorescent imaging. The
      translocation of fluorescently labeled proOmpA was largely independent on the
      position and the size of the fluorescent label (up to a size of 13-16 A). A
      fluorophore at the +4 position blocked translocation, but inhibition was
      completely relieved in the PrlA4 mutant. The kinetics of translocation of the
      fluorescently labeled proOmpA could be directly monitored by means of
      fluorescence quenching. Inner membrane vesicles containing wild-type SecYEG were
      found to translocate proOmpA with a turnover of 4.5 molecules proOmpA/SecYEG
      complex/min and an apparent K(m) of 180 nm, whereas the PrlA4 mutant showed an
      almost 10-fold increase in turnover rate and a 3-fold increase of the apparent
      K(m) for proOmpA translocation.

PMID- 12226102
TI  - Ligand-independent trans-activation of the platelet-derived growth factor
      receptor by reactive oxygen species requires protein kinase C-delta and c-Src.
AB  - Reactive oxygen species are involved in the mitogenic signal transduction
      cascades initiated by several growth factors and play a critical role in
      mediating cardiovascular diseases. Interestingly, H(2)O(2) induces tyrosine
      phosphorylation and trans-activation of the platelet-derived growth factor
      receptor and the epidermal growth factor receptor in many cell lines including
      vascular smooth muscle cells. To investigate the molecular mechanism by which
      reactive oxygen species contribute to vascular diseases, we have examined a
      signal transduction cascade involved in H(2)O(2)-induced platelet-derived growth
      factor receptor activation in vascular smooth muscle cells. We found that
      H(2)O(2) induced a ligand-independent phosphorylation of the platelet-derived
      growth factor-beta receptor at Tyr(1021), a phospholipase C-gamma binding site,
      involving the requirement of protein kinase C-delta and c-Src that is distinct
      from a ligand-dependent autophosphorylation. Also, H(2)O(2) induced the
      association of protein kinase C-delta with the platelet-derived growth factor
      beta receptor and c-Src in vascular smooth muscle cells. These findings will
      provide new mechanistic insights by which enhanced reactive oxygen species
      production in vascular smooth muscle cells induces unique alleys of signal
      transduction distinct from those induced by endogenous ligands leading to an
      abnormal vascular remodeling process.

PMID- 12226103
TI  - The extracellular N terminus of the endothelin B (ETB) receptor is cleaved by a
      metalloprotease in an agonist-dependent process.
AB  - The extracellular N terminus of the endothelin B (ET(B)) receptor is susceptible
      to limited proteolysis (cleavage at R64 downward arrow S65), but the regulation
      and the functional consequences of the proteolysis remain elusive. We analyzed
      the ET(B) receptor or an ET(B)-GFP fusion protein stably or transiently expressed
      in HEK293 cells. After incubation of cells at 4 degrees C, only the full-length
      ET(B) receptor was detected at the cell surface. However, when cells were
      incubated at 37 degrees C, N-terminal cleavage was observed, provided endothelin
      1 was present during the incubation. Cleavage was not inhibited by
      internalization inhibitors (sucrose, phenylarsine oxide). However, in cells
      incubated with both internalization inhibitors and metalloprotease inhibitors
      (batimastat, inhibitor of TNFalpha-convertase) or metal chelators (EDTA,
      phenanthroline), the cleavage was blocked, indicating that metalloproteases
      cleave the agonist-occupied ET(B) receptor at the cell surface. Functional
      analysis of a mutant ET(B) receptor lacking the first 64 amino acids ([Delta2
      64]ET(B) receptor) revealed normal functional properties, but a 15-fold reduced
      cell surface expression. The results suggest a role of the N-terminal proteolysis
      in the regulation of cell surface expression of the ET(B) receptor. This is the
      first example of a multispanning membrane protein, which is cleaved by a
      metalloprotease, but retains its functional activity and overall structure.

PMID- 12226105
TI  - Kinetic pathway of dTTP hydrolysis by hexameric T7 helicase-primase in the
      absence of DNA.
AB  - Bacteriophage T7 gp4A' protein is a hexameric helicase-primase protein that
      separates the strands of a duplex DNA in a reaction coupled to dTTP hydrolysis.
      Here we reexamine in more detail the kinetic mechanism of dTTP hydrolysis by a
      preassembled T7 helicase hexamer in the absence of DNA. Pre-steady state dTTP
      hydrolysis kinetics showed a distinct burst whose amplitude indicated that a
      preformed hexamer of T7 helicase hydrolyzes on an average one dTTP per hexamer.
      The pre-steady state chase-time experiments provided evidence for sequential
      hydrolysis of two dTTPs. The medium [(18)O]P(i) exchange experiments failed to
      detect dTTP synthesis, indicating that the less than six-site hydrolysis observed
      is not due to reversible dTTP hydrolysis on the helicase active site. The P(i)
      release rate was measured directly using a stopped-flow fluorescence assay, and
      it was found that the rate of dTTP hydrolysis on the helicase active site is
      eight times faster than the P(i)-release rate, which in turn is three times
      faster than the dTDP release rate. Thus, the rate-limiting step in the pathway of
      helicase-catalyzed deoxythymidine triphosphatase (dTTPase) reaction is the
      release of dTDP. Chase-time dTTPase kinetics in the steady state phase provided
      evidence for two to three slowly hydrolyzing dTTPase sites on the hexamer. The
      results of this study are therefore consistent with those reported earlier
      (Hingorani, M. M., Washington, M. T., Moore, K. C., and Patel, S. S. (1997) Proc.
      Natl. Acad. Sci. U.S.A. 94, 5012-5017), and they support a model of dTTP
      hydrolysis by T7 helicase hexamer that is similar to the binding change mechanism
      of F(1)-ATPase with dTTP hydrolysis occurring sequentially at the catalytic
      sites.

PMID- 12226106
TI  - Multiple mechanisms of transcription inhibition by ppGpp at the lambdap(R)
      promoter.
AB  - General stress conditions in bacterial cells cause a global cellular response
      called the stringent response. The first event in this control is production of
      large amounts of a regulatory nucleotide, guanosine-3',5'-(bis)pyrophospahte
      (ppGpp). It was proposed recently that ppGpp acts by decreasing stability of open
      complexes at promoters that make short-lived open complexes, e.g. the rRNA
      promoters. However, here we report that the bacteriophage lambdap(R) promoter,
      which forms long-lived open complexes, is inhibited by ppGpp in vitro as observed
      in vivo. We performed a systematic investigation of the ppGpp-specific inhibition
      of transcription initiation at lambdap(R) and found that ppGpp does decrease
      stability of open complexes at lambdap(R), but only slightly. Likewise the
      equilbrium binding constant and rate of open complex formation by RNA polymerase
      at lambdap(R) are only slightly affected by ppGpp. The major effect of ppGpp
      mediated inhibition is to decrease the rate of promoter escape. We conclude that
      ppGpp-mediated inhibition of transcription initiation is not restricted to
      promoters that make short-lived open complexes. Rather we conclude that the
      initial catalytic step of transcript formation is affected by ppGpp, specifically
      formation of the first phosphodiester bond is inhibited by ppGpp at lambdap(R).

PMID- 12226108
TI  - Tumor suppressor activity of AP2alpha mediated through a direct interaction with
      p53.
AB  - The AP2 transcription factor family is a set of developmentally regulated,
      retinoic acid inducible genes composed of four related factors, AP2alpha,
      AP2beta, AP2gamma, and AP2delta. AP2 factors orchestrate a variety of cell
      processes including apoptosis, cell growth, and tissue differentiation during
      embryogenesis. In studies of primary malignancies, AP2alpha has been shown to
      function as a tumor suppressor in breast cancer, colon cancer, and malignant
      melanoma. In cell culture models, overexpression of AP2alpha inhibits cell
      division and stable colony formation, whereas, a dominant-negative AP2alpha
      mutant increases invasiveness and tumorigenicity. Here we show that AP2alpha
      targets the p53 tumor suppressor protein. Studies with chromatin
      immunoprecipitation demonstrate that AP2alpha is brought to p53 binding sites in
      p53-regulated promoters. The interaction between AP2alpha and p53 augments p53
      mediated transcriptional activation, which results in up-regulation of the cyclin
      dependent kinase inhibitor p21(WAF1/CIP1). AP2alpha is able to induce G(1) and
      G(2) cell cycle arrest only in the presence of wild-type p53. Thus, we conclude
      that the tumor suppressor activity of AP2alpha is mediated through a direct
      interaction with p53. These results also provide a mechanism to explain patterns
      of gene expression in cancers where AP2alpha is known to function as a tumor
      suppressor.

PMID- 12226107
TI  - Dual-substrate specificity short chain retinol dehydrogenases from the vertebrate
      retina.
AB  - Retinoids are chromophores involved in vision, transcriptional regulation, and
      cellular differentiation. Members of the short chain alcohol
      dehydrogenase/reductase superfamily catalyze the transformation of retinol to
      retinal. Here, we describe the identification and properties of three enzymes
      from a novel subfamily of four retinol dehydrogenases (RDH11-14) that display
      dual-substrate specificity, uniquely metabolizing all-trans- and cis-retinols
      with C(15) pro-R specificity. RDH11-14 could be involved in the first step of all
      trans- and 9-cis-retinoic acid production in many tissues. RDH11-14 fill the gap
      in our understanding of 11-cis-retinal and all-trans-retinal transformations in
      photoreceptor (RDH12) and retinal pigment epithelial cells (RDH11). The dual
      substrate specificity of RDH11 explains the minor phenotype associated with
      mutations in 11-cis-retinol dehydrogenase (RDH5) causing fundus albipunctatus in
      humans and engineered mice lacking RDH5. Furthermore, photoreceptor RDH12 could
      be involved in the production of 11-cis-retinal from 11-cis-retinol during
      regeneration of the cone visual pigments. These newly identified enzymes add new
      elements to important retinoid metabolic pathways that have not been explained by
      previous genetic and biochemical studies.

PMID- 12226110
TI  - Keys to success: WHO's world report on violence and health, Montreal declaration,
      motor vehicle injuries.

PMID- 12226109
TI  - Molecular and biochemical characterization of two plant inositol polyphosphate 6
      /3-/5-kinases.
AB  - Despite the high deposition of inositol hexakisphosphate (IP(6)), also known as
      phytate or phytin, in certain plant tissues little is known at the molecular
      level about the pathway(s) involved in its production. In budding yeast, IP(6)
      synthesis occurs through the sequential phosphorylation of I(1,4,5)P(3) by two
      gene products, Ipk2 and Ipk1, a IP(3)/IP(4) dual-specificity 6-/3-kinase and an
      inositol 1,3,4,5,6-pentakisphosphate 2-kinase, respectively. Here we report the
      identification and characterization of two inositol polyphosphate kinases from
      Arabidopsis thaliana, designated AtIpk2alpha and AtIpk2beta that are encoded by
      distinct genes on chromosome 5 and that are ubiquitously expressed in mature
      tissue. The primary structures of AtIpk2alpha and AtIpk2beta are 70% identical to
      each other and 12-18% identical to Ipk2s from yeast and mammals. Similar to yeast
      Ipk2, purified recombinant AtIpk2alpha and AtIpk2beta have 6-/3-kinase activities
      that sequentially phosphorylate I(1,4,5)P(3) to generate I(1,3,4,5,6)P(5)
      predominantly via an I(1,4,5,6)P(4) intermediate. While I(1,3,4,5)P(4) is a
      substrate for the plant Ipk2s, it does not appear to be a detectable product of
      the IP(3) reaction. Additionally, we report that the plant and yeast Ipk2 have a
      novel 5-kinase activity toward I(1,3,4,6)P(4) and I(1,2,3,4,6)P(5), which would
      allow these proteins to participate in at least two proposed pathways in the
      synthesis of IP(6). Heterologous expression of either plant isoform in an ipk2
      mutant yeast strain restores IP(4) and IP(5) production in vivo and rescues its
      temperature-sensitive growth defects. Collectively our results provide a
      molecular basis for the synthesis of higher inositol polyphosphates in plants
      through multiple routes and indicate that the 6-/3-/5-kinase activities found in
      plant extracts may be encoded by the IPK2 gene class.

PMID- 12226112
TI  - Guns in the world: old news and new news.

PMID- 12226111
TI  - Injury prevention and indigenous peoples.

PMID- 12226113
TI  - Trends in BB/pellet gun injuries in children and teenagers in the United States,
      1985-99.
AB  - OBJECTIVE: To characterize national trends in non-fatal BB/pellet gun related
      injury rates for persons aged 19 years or younger in relation to trends in non
      fatal and fatal firearm related injury rates and discuss these trends in light of
      injury prevention and violence prevention efforts. SETTING: The National
      Electronic Injury Surveillance System (NEISS) includes approximately 100
      hospitals with at least six beds that provide emergency services. These hospitals
      comprise a stratified probability sample of all US hospitals with emergency
      departments. The National Vital Statistics System (NVSS) is a complete census of
      all death certificates filed by states and is compiled annually. METHODS:
      National data on BB/pellet gun related injuries and injury rates were examined
      along with fatal and non-fatal firearm related injuries and injury rates. Non
      fatal injury data for all BB/pellet gun related injury cases from 1985 through
      1999, and firearm related injury cases from 1993 through 1999 were obtained from
      hospital emergency department records using the NEISS. Firearm related deaths
      from 1985 through 1999 were obtained from the NVSS. RESULTS: BB/pellet gun
      related injury rates increased from age 3 years to a peak at age 13 years and
      declined thereafter. In contrast, firearm related injury and death rates
      increased gradually until age 13 and then increased sharply until age 18 years.
      For persons aged 19 years and younger, BB/pellet gun related injury rates
      increased from the late 1980s until the early 1990s and then declined until 1999;
      these injury rates per 100 000 population were 24.0 in 1988, 32.8 in 1992, and
      18.3 in 1999. This trend was similar to those for fatal and non-fatal firearm
      related injury rates per 100 000 which were 4.5 in 1985, 7.8 in 1993, and 4.3 in
      1999 (fatal) and 38.6 in 1993 and 16.3 in 1999 (non-fatal). In 1999, an estimated
      14 313 (95% confidence interval (CI) 12 025 to 16 601) cases with non-fatal
      BB/pellet gun injuries and an estimated 12 748 (95% CI 7881-17 615) cases with
      non-fatal firearm related injuries among persons aged 19 years and younger were
      treated in US hospital emergency departments. CONCLUSIONS: BB/pellet gun related
      and firearm related injury rates show similar declines since the early 1990s.
      These declines coincide with a growing number of prevention efforts aimed at
      reducing injuries to children from unsupervised access to guns and from youth
      violence. Evaluations at the state and local level are needed to determine true
      associations.

PMID- 12226114
TI  - Study of the effectiveness of the US safety standard for child resistant
      cigarette lighters.
AB  - OBJECTIVE: The purpose of this research is to evaluate the effectiveness of the
      US Consumer Product Safety Commission's (CPSC) Safety Standard for Cigarette
      Lighters, which requires that disposable cigarette lighters be resistant to
      operation by children younger than age 5. METHODS: Fire data on children playing
      with lighters were solicited from selected US fire departments for incidents
      occurring from 1997-99, to identify the proportion of such fires caused by
      children younger than age 5 playing with cigarette lighters. These data were
      compared with similar data from 1985-87. An odds ratio was used to determine if
      there was a significant decrease in cigarette lighter fires caused by children
      younger than age 5 compared to children ages 5 and older. To estimate fires that
      would have occurred without the standard, the odds ratio, adjusted for
      population, was applied to 1998 national estimates of fires occurring. National
      estimates of 1998 fire losses were based on data from the National Fire Incident
      Reporting System and the National Fire Protection Association to which the 1997
      99 age and lighter type distributions were applied. The difference between the
      fire losses that would have occurred and those that did occur represented fire
      losses prevented. RESULTS: In the post-standard study, 48% of the cigarette
      lighter fires were started by children younger than age 5, compared with 71% in
      the pre-standard study. The odds ratio of 0.42 was statistically significant
      (p<0.01). This represented a 58% reduction in fires caused by the younger age
      group compared to the older age group. When applied to national fire loss data,
      an estimated 3300 fires, 100 deaths, 660 injuries, and $52.5 million in property
      loss were prevented by the standard in 1998, totaling $566.8 million in 1998
      societal savings. CONCLUSIONS: The CPSC standard requiring child resistant
      cigarette lighters has reduced fire deaths, injuries, and property loss caused by
      children playing with cigarette lighters and can be expected to prevent
      additional fire losses in subsequent years.

PMID- 12226115
TI  - What distinguishes unintentional injuries from injuries due to intimate partner
      violence: a study in Greek ambulatory care settings.
AB  - OBJECTIVES: Intimate partner violence (IPV) is an important sociocultural and
      public health problem. This study aims to assess sociodemographic and injury
      characteristics of IPV victims among adults in a traditional southern European
      population. SETTING: Accident and emergency departments of three sentinel
      hospitals in Greece participating in the Emergency Department Injury Surveillance
      System (EDISS). METHODS: Data on sociodemographic variables, as well as event and
      injury characteristics were retrieved from the EDISS database during the three
      year period 1996-98. Out of a total of 27 319 injured women aged 19 years or
      more, 312 (1.1%) were reported as IPV related and were compared with 26 466 women
      with unintentional injuries. Among the 35 174 men with injuries 39 (0.1%) were
      reported as IPV related and were compared with 34 049 men with unintentional
      injuries. The data were analyzed through simple cross tabulations and multiple
      logistic regression. Positive predicted values for selected injury
      characteristics were also calculated. RESULTS: IPV is more common in rural than
      in urban areas of Greece. Women are 10 times more frequently IPV victims but men
      are also IPV victims; younger women and older men are disproportionately affected
      by IPV. The relative frequency of the phenomenon increases during the late
      evening and night hours. Certain types of injuries, notably multiple facial
      injuries, and presentation of the injured person on his/her own at the emergency
      department or combinations of predictive characteristics are strongly indicative
      of IPV. CONCLUSIONS: Injuries due to IPV are not uncommon in Greece, not
      withstanding the traditional structure of the society and the tendency of under
      reporting. Certain injury characteristics have high positive predictive values
      and could be used in screening protocols aiming at the correct identification of
      the underlying external cause in injuries that may be caused by IPV.

PMID- 12226116
TI  - Hip protector compliance among older people living in residential care homes.
AB  - OBJECTIVES: To estimate the compliance rates for the use of hip protectors among
      people living in residential care homes. Population/setting: People aged 65 years
      and over living in residential care homes with 20 or more beds in East Kent,
      south east England. METHODS: Seventeen homes with the highest historical
      frequency of hip fractures were selected. All residents were offered SAFEHIP hip
      protectors. Care staff recorded daily hip protector compliance on diary cards
      over six months. Compliance rates were estimated from the number of sessions
      (morning, afternoon, evening, night) that a person wore hip protectors. RESULTS:
      A total of 153 (51%) out of 299 residents agreed to wear hip protectors The 24
      hour compliance rate for those who were issued with hip protectors and wore them
      at least once was 29%: 37% in the daytime and 3% at night. Daytime compliance
      rates reduced from 47% for the first month, to around 30% for months 5 and 6.
      CONCLUSION: This study highlights the problems of persuading older people living
      in residential care homes to wear hip protectors. They have been shown to prevent
      hip fracture in nursing home (high risk) populations, and a recent trial showed
      their effectiveness in a mixed geriatric population. People living in residential
      care homes are also at greater risk of falling and fracturing than their
      counterparts living in the community. Initiatives to prevent hip fracture within
      residential care homes are also justified.

PMID- 12226117
TI  - Characteristics of pregnant women in motor vehicle crashes.
AB  - OBJECTIVES: Motor vehicle crashes are the leading cause of hospitalized trauma
      during pregnancy. Maternal injury puts the fetus at great risk, yet little is
      known about the incidence, risks, and characteristics of pregnant women in
      crashes. SETTING AND METHODS: Police reported crashes were analyzed from the
      National Automotive Sampling System Crashworthiness Data System. Since 1995, this
      system recorded pregnancy/trimester status. Pregnant and non-pregnant women 15-39
      years of age were compared by age, driver status, seat belt use, and treatment.
      Belt use and seating position were examined by trimester. RESULTS: There were 427
      pregnant occupants identified (weighted n=32 810, 2.6%, SE 12 585, rate 13/1000
      person years). The mean age was 24.9 compared with 24.8 years (pregnant v non
      pregnant). Cases were distributed by trimester as follows: first 29.8%, second
      36.4%, and third 33.8%. Pregnant women were drivers 70% of the time compared with
      71% for non-pregnant women. No belt use was 14% compared with 13% (pregnant v non
      pregnant). Mean injury severity was lower for pregnant women but they were more
      likely to transported or hospitalized. Improper belt use decreased after the
      first trimester and there was little change in driver proportion by trimester.
      Third trimester hospitalization rates increased. CONCLUSIONS: Pregnant occupants
      in crashes have similar profiles of restraint use, driver status, and seat
      position but different treatment indicators compared to non-pregnant occupants.
      Trimester status has relatively little impact on crash risk, seating position or
      restraint use. Undercounting of pregnant cases was possible, even so, 1% of all
      births were reported to be involved in utero in crashes. Little research has
      focused on developmental outcomes to infants and children previously involved in
      exposure to these crashes.

PMID- 12226118
TI  - Trends in road injury hospitalisation rates for Aboriginal and non-Aboriginal
      people in Western Australia, 1971-97.
AB  - OBJECTIVE: To examine trends in road injury hospitalisation rates for Aboriginal
      and non-Aboriginal people in Western Australia. METHODS: Data from the Western
      Australian Hospital Morbidity Data System for the years between 1971 and 1997
      were analysed. Poisson regression models were fitted to determine whether the
      trends were significant. RESULTS: The rate of hospitalisation due to road injury
      for Aboriginal people (719.1 per 100 000 population per year) over the time
      period examined was almost twice as high as that for non-Aboriginal people (363.4
      per 100 000 population per year). Overall, the results showed that while
      hospitalisations from road injury involving non-Aboriginal people have been
      decreasing by 6.7% per three year period since 1971, the rates of hospitalisation
      for Aboriginal people have been increasing by 2.6% per three year period. Both of
      these trends were statistically significant. The alarming increasing trend
      observed for Aboriginal people was more pronounced in males, those aged 0-14
      years and over 45 years, and for those living in rural areas. CONCLUSIONS: As the
      rates of road injury for Aboriginal people are higher than for non-Aboriginal
      people, and are also following an increasing trend, road safety issues involving
      Aboriginal people need to be addressed urgently by health and transport
      authorities.

PMID- 12226119
TI  - Pediatric motor vehicle related injuries in the Navajo Nation: the impact of the
      1988 child occupant restraint laws.
AB  - BACKGROUND: Navajo motor vehicle mortality is the highest among the 12 Indian
      Health Service (IHS) administrative areas. In July 1988, the Navajo Nation
      enacted a primary enforcement safety belt use and a child restraint law.
      OBJECTIVE: Assess the impact of the laws on the rate and severity of pediatric (0
      19 years) motor vehicle injury resulting in hospitalizations in the Navajo
      Nation. METHODS: Hospitalizations associated with motor vehicle related injury
      discharges were identified by International Classification of Diseases, 9th
      revision, CM E codes, 810-825 (.0,.1) from the Navajo IHS hospital discharge
      database. Age specific rates for the period before the law, 1983-88, were
      compared with those after enactment and enforcement, 1991-95. Severity of injury,
      measured by the abbreviated injury scale (AIS) score and new injury severity
      score (NISS), was determined with ICDMAP-90 software. Wilcoxon rank sum and
      chi(2) tests were used for analysis. RESULTS: Discharge rates (SE) for motor
      vehicle injury (per 100 000) decreased significantly in all age groups: 0-4 years
      (62 (7) to 28 (4)), 5-11 years (55.3 (6) to 26 (4)), and 15-19 years (139 (14) to
      68 (7)); p=0.0001. In children 0-4 years, the median AIS score decreased from 1.5
      (1,3) (25th, 75th centile) to 1 (1,2), p=0.06, and the median NISS decreased from
      3.5 (1,9) to 2 (1,5), p=0.07. The proportion of children with NISS scores >4
      decreased significantly for the 0-4 year age group (p=0.03). CONCLUSIONS:
      Concurrent with enactment of the Navajo Nation occupant and child restraint laws
      there was a reduction in the rate of motor vehicle related hospital discharges
      for children. Severity of injury declined in very young Navajo children. The
      effect of enactment and enforcement of this Native American child occupant
      restraint law may serve as an example of an effective injury control effort
      directed at Native American children.

PMID- 12226120
TI  - Drinking histories of fatally injured drivers.
AB  - CONTEXT: About 30% of drivers killed in crashes have high blood alcohol
      concentrations (BACs) of 0.10+ g/dl. There is a question about whether these
      drivers primarily are problem drinkers who chronically drink and drive-the so
      called hard core drinking drivers. OBJECTIVE: To investigate drinking histories
      of fatally injured drivers in relation to their BACs. DESIGN AND PARTICIPANTS:
      Retrospective cohort study of 818 fatally injured drivers who were included in
      the 1993 National Mortality Followback Survey (a national sample of US deaths in
      which next of kin were interviewed) and whose BACs were recorded by the Fatality
      Analysis Reporting System, a census of US traffic deaths. MAIN OUTCOME MEASURE:
      Problem drinking indicators. RESULTS: At least one indicator of potential problem
      drinking, primarily heavy drinking, was reported for 68% of drivers with very
      high BACs (0.15+ g/dl), 41% with BACs of 0.10-0.14 g/dl, 32% with BACs of 0.01
      0.09 g/dl, and 7% with zero BACs. Spouses provided more credible responses than
      other relatives: they were more likely to report at least occasional drinking and
      driving among deceased drivers with high BACs. For the most direct signs of
      problem drinking (described as a problem drinker during the last month of life or
      frequently driving after having five or more drinks), spousal reports suggested
      the prevalence of problem drinking among drivers with very high BACs was 22%
      (having both indicators), 32% (frequently driving after having five or more
      drinks), 44% (described as problem drinker), or 57% (having either indicator).
      CONCLUSIONS: Drivers with BACs of 0.10+ g/dl were far more likely than sober
      drivers to be described as having markers of problem drinking. However, many did
      not have indicators suggestive of problem drinking. In addition to programs
      focused on repeat offenders or problem drinkers, countermeasures such as sobriety
      checkpoints that target a broader spectrum of drinking drivers are appropriate.

PMID- 12226121
TI  - Prevalence of youth access to alcohol or a gun in the home.
AB  - OBJECTIVES: To estimate the national prevalence of youth access to alcohol, a
      gun, or both alcohol and a gun, in their home and to describe the demographic
      characteristics associated with access to either alcohol or a gun. METHODS: Cross
      sectional data from the 1995 in-home survey of the National Longitudinal Study of
      Adolescent Health, which used a nationally representative randomly selected
      school based sample (n=18 924) of adolescents in grades 7-12, were analyzed. The
      current analyses were restricted to those adolescents 12-18 years of age (n=18
      454). Crude logistic regression analyses was used to determine the demographic
      characteristics associated with access to alcohol or a gun in the home. RESULTS:
      Overall, 28.7% of US adolescents reported having easy access to alcohol in the
      home. Availability of alcohol was associated with race/ethnicity, mother's
      education, family structure, and welfare status. Similarly, 24.3% of US
      adolescents reported easy access to a gun in the home. Availability of a gun in
      the home was associated with gender, race/ethnicity, mother's education, family
      structure, and welfare status. Among those that reported that a gun was available
      in their home, most reported availability of a shotgun (63.0%) followed by a
      rifle (61.3%), handgun (57.3%), and other gun (16.4%). Ten per cent of
      adolescents reported availability of both alcohol and a gun in their home.
      CONCLUSIONS: One quarter of US adolescents reported easy access to either alcohol
      or a gun in their home. Given the risks associated with the misuse of alcohol and
      guns among adolescents, efforts to increase public awareness of the availability
      of alcohol and guns in the home are needed.

PMID- 12226122
TI  - Exposure to traffic among urban children injured as pedestrians.
AB  - OBJECTIVES: To explore the immediate pre-crash activities and the routine traffic
      exposure (street crossing and play) in a sample of urban children struck by
      automobiles. In particular, the traffic exposure of children who were struck
      while playing was compared with that of those struck while crossing streets.
      DESIGN: Cross sectional survey. SETTING: Urban pediatric emergency department.
      PATIENTS: A total of 139 children ages 4-15 years evaluated for acute injuries
      resulting from pedestrian-motor vehicle collisions during a 14 month period. MAIN
      OUTCOME MEASURES: Sites of outdoor play, daily time in outdoor play, weekly
      number of street crossings, pre-crash circumstance (play v walking). RESULTS:
      Altogether 39% of the children routinely used the street and 64% routinely used
      the sidewalks as play areas. The median number of street crossings per week per
      child was 27. There were no differences in exposures for the 29% who were hit
      while playing compared with the 71% who were hit while walking. Although 84% of
      the children walked to or from school at least one day per week, only 15% of the
      children were struck while on the school walking trip. The remainder were injured
      either while playing outdoors or while walking to other places. CONCLUSIONS:
      Urban children who are victims of pedestrian crashes have a high level of traffic
      exposure from a variety of circumstances related to their routine outdoor playing
      and street crossing activities. The distributions of traffic exposures were
      similar across the sample, indicating that the sample as a whole had high traffic
      exposure, regardless of the children's activity preceding the crash. Future
      pedestrian injury programs should address the pervasive nature of children's
      exposure to traffic during their routine outdoor activities.

PMID- 12226123
TI  - Do criminals go to the hospital when they are shot?
AB  - OBJECTIVES: To determine whether criminals go to the hospital when they are shot.
      Such information is needed to check on the accuracy of using hospital emergency
      room data to estimate non-fatal gunshot wounds. SETTING: Five jails across the
      US. METHODS: A survey of inmates being booked into jail, administered by in-house
      health care staff. RESULTS: Over 90% of over 300 criminals who had been wounded
      sometime before their incarceration reported going to a hospital for treatment
      after being shot. These results are consistent with previous findings from one
      jail. CONCLUSIONS: Jail inmates who had previously been shot were likely to have
      been treated in a hospital. This limited finding is consistent with the
      proposition that hospital/emergency department data may miss only a small
      percentage of gunshot wounds to criminals.

PMID- 12226124
TI  - Are squash players protecting their eyes?
AB  - OBJECTIVE: To determine factors associated with adult squash players' protective
      eyewear behaviours. METHODS: A survey of 303 players (aged >or =18 years) was
      conducted at three squash venues in Melbourne, Australia over a three week period
      in June 2000 to obtain information about protective eyewear use. RESULTS: Of 303
      participants the response rate was 98.1%; 66.1% were males, with a mean age of
      40.5 years. The majority (68.4%) had played squash for 10 years or more. Although
      18.8% of players reported using protective eyewear, only 8.9% reported wearing
      approved eyewear. Both age group (p<0.05) and years of squash experience (p<0.01)
      were significantly associated with any eyewear use. The two main influences were
      personal experience of eye injuries (50.0%) and knowledge of eye injury risk
      (33.9%). A commonly reported barrier was restriction of vision (34.2%).
      CONCLUSION: These findings demonstrate a low prevalence of voluntary use of
      appropriate protective eyewear. Future prevention strategies incorporating
      education campaigns should focus on increasing players' knowledge of risks. The
      barriers to use and misconceptions about which types of eyewear is most
      protective need to be addressed as a priority.

PMID- 12226125
TI  - Association between the inception of a SAFE KIDS Coalition and changes in
      pediatric unintentional injury rates.
AB  - OBJECTIVE: To assess the relationship between the implementation of a SAFE KIDS
      Coalition and pediatric unintentional injury rates. SETTING: Shelby County,
      Tennessee. DESIGN: Retrospective observational analysis. PATIENTS: County
      residents nine years of age or younger presenting to the children's medical
      center, its emergency department, or its outpatient clinics from 1990-97.
      INTERVENTION: Implementation of a SAFE KIDS Coalition. MAIN OUTCOME MEASURES:
      Rates of unintentional injuries targeted by the SAFE KIDS Coalition that resulted
      in hospitalization or in death. Rates of motor vehicle occupant injuries that
      resulted in hospitalization or in death. Rates of non-targeted unintentional
      injuries, namely injuries secondary to animals and by exposure to toxic plants.
      Rates of severe injuries (defined as those targeted injuries that required
      hospitalization or resulted in death), and specifically, severe motor vehicle
      occupant injuries were compared before and after the inception of the coalition
      using Poisson regression analysis. RESULTS: The relative risk of targeted severe
      injury rates decreased after implementation of the coalition even after
      controlling for changes in hospital admission rates. Specifically, severe motor
      vehicle occupant injury rates decreased 30% (relative risk 0.70; 95% confidence
      interval 0.54 to 0.89) after initiation of the coalition. CONCLUSIONS: The
      implementation of a SAFE KIDS Coalition was associated with a decrease in severe
      targeted injuries, most notably, severe motor vehicle occupant injuries. Although
      causality cannot be determined, these data suggest that the presence of a
      coalition may be associated with decreased severe unintentional injury rates.

PMID- 12226126
TI  - Recording of community violence by medical and police services.
AB  - OBJECTIVES: To determine the extent to which community violence that results in
      injury treated in emergency departments appears in official police records and to
      identify age/gender groups at particular risk of under-recording by the police.
      METHODS: Non-confidential data for patients with assault related injury treated
      in the emergency departments of two hospitals in one South Wales city (Swansea)
      during a six month period were compared with data relating to all recorded crimes
      in the category "Violence against the person" in the police area where the
      hospitals were located. RESULTS: Over the six month period a total of 1513
      assaults were recorded by Swansea emergency departments and the police (1019,
      67.3% injured males and 494, 32.7% injured females). The majority of these
      assaults (993, 65.6%) were recorded exclusively by emergency departments; 357
      (23.6%) were recorded only by the police and 163 (10.8%) were recorded by both
      emergency departments and the police. Equal proportions of males (67.3%) and
      females (67.5%) injured in assaults were recorded by both emergency departments
      and the police, but men were more likely to have their assault recorded
      exclusively in emergency departments (odds ratio (OR) 2.1, 95% confidence
      interval (CI) 1.7 to 2.7) while women were more likely to have their assault
      recorded exclusively by the police (OR 2.5, 95% CI 2.0 to 3.2). There were no
      significant relationships between exclusive emergency department recording and
      increasing age (OR 1.0, 95% CI 0.9 to 1.2), exclusive police recording and
      increasing age (OR 1.1, 95% CI 1.0 to 1.2), or between age and dual recording (OR
      0.9, 95% CI 0.8 to 1.0). CONCLUSIONS: Most assaults leading to emergency
      department treatment, particularly in which males were injured, were not recorded
      by the police. Assaults on the youngest group (0-10, particularly boys) were
      those least likely to be recorded by police and females over age 45, the most
      likely. Emergency department derived assault data provide unique perspectives of
      community violence and police detection.

PMID- 12226127
TI  - How old is that child? Validating the accuracy of age assignments in
      observational surveys of vehicle restraint use.
AB  - OBJECTIVES: Many large scale observational studies of child restraint usage
      require observers to estimate the ages of the vehicle occupants. The accuracy of
      age assignments were assessed and possible methods to improve observational
      accuracy in research and field studies of child restraint use were identified.
      METHODS: The validation study was performed at fast food restaurants in a
      metropolitan area. Three, two person teams observed 449 occupants of vehicles
      with at least one child passenger. The drivers were then interviewed to obtain
      the actual ages of the vehicle occupants. The primary outcome measure was the per
      cent of age assignments that were correct by age category (infant, toddler,
      school age, teen, adult). The observers had previously conducted a statewide
      child restraint observation study and were trained in estimating age categories.
      RESULTS: A total of 391 (87%) of the 449 occupants were assigned to their correct
      age categories. Incorrect assignments were more common among infants (22%
      incorrect), but few infants (nine) were observed. The most frequent error was
      classifying adults (19 years and older) as teenagers (13-18 years). CONCLUSION:
      Trained, experienced observers approached 90% accuracy in their assignment of
      children to specific age categories. Additional study is required to determine
      whether these results are applicable to different age categories and observers.
      It is recommended that the National Highway Traffic Safety Administration, the
      Centers for Disease Control and Prevention, state and local agencies, and other
      sponsors of observational surveys consider observer competence as an important
      variable. The validity of age assignments can be assessed by randomly
      interviewing a sample of drivers. More accurate age estimates will improve
      decisions regarding prevention programs, funding, and policies.

PMID- 12226128
TI  - Underestimates of unintentional firearm fatalities: comparing Supplementary
      Homicide Report data with the National Vital Statistics System.
AB  - OBJECTIVE: A growing body of evidence suggests that the nation's vital statistics
      system undercounts unintentional firearm deaths that are not self inflicted. This
      issue was examined by comparing how unintentional firearm injuries identified in
      police Supplementary Homicide Report (SHR) data were coded in the National Vital
      Statistics System. METHODS: National Vital Statistics System data are based on
      death certificates and divide firearm fatalities into six subcategories:
      homicide, suicide, accident, legal intervention, war operations, and
      undetermined. SHRs are completed by local police departments as part of the FBI's
      Uniform Crime Reports program. The SHR divides homicides into two categories:
      "murder and non-negligent manslaughter" (type A) and "negligent manslaughter"
      (type B). Type B shooting deaths are those that are inflicted by another person
      and that a police investigation determined were inflicted unintentionally, as in
      a child killing a playmate after mistaking a gun for a toy. In 1997, the SHR
      classified 168 shooting victims this way. Using probabilistic matching, 140 of
      these victims were linked to their death certificate records. RESULTS: Among the
      140 linked cases, 75% were recorded on the death certificate as homicides and
      only 23% as accidents. CONCLUSION: Official data from the National Vital
      Statistics System almost certainly undercount firearm accidents when the victim
      is shot by another person.

PMID- 12226129
TI  - Evaluation of the THINK FIRST For KIDS injury prevention curriculum for primary
      students.
AB  - THINK FIRST is a national non-profit organization whose mission is to educate
      young people about the prevention of brain and spinal cord injuries. This paper
      describes a study conducted by THINK FIRST of Oregon on one of its injury
      prevention curricula, THINK FIRST for KIDS.

PMID- 12226130
TI  - Visual impairment and risk of falls and fracture.

PMID- 12226131
TI  - The Barell matrix.

PMID- 12226133
TI  - Liver-fat accumulation and insulin resistance in obese women with previous
      gestational diabetes.
AB  - OBJECTIVE: We determined whether fat accumulation in the liver is associated with
      features of insulin resistance independent of obesity. RESEARCH METHODS AND
      PROCEDURES: We recruited 27 obese nondiabetic women in whom liver fat (LFAT)
      content was determined by proton spectroscopy, intra-abdominal and subcutaneous
      fat by magnetic resonance imaging, and insulin sensitivity by the euglycemic
      insulin clamp technique. The women were divided based on their median LFAT
      content (5%) to groups with low (3.2 +/- 0.3%) and high (9.8 +/- 1.5%) liver fat.
      The groups were almost identical with respect to age (36 +/- 1 vs. 38 +/- 1 years
      in low vs. high-LFAT), body mass index (32.2 +/- 0.6 vs. 32.8 +/- 0.5 kg/m(2)),
      waist-to-hip ratio, intra-abdominal, subcutaneous, and total fat content.
      RESULTS: Women with high LFAT had features of insulin resistance including higher
      fasting serum triglyceride (1.93 +/- 0.21 vs. 1.11 +/- 0.09 mM, p < 0.01) and
      insulin (14 +/- 3 vs. 10 +/- 1 mU/L, p < 0.05) concentrations than women with low
      LFAT. The group with high LFAT also had higher 24-hour blood pressures, and lower
      whole-body insulin sensitivity compared with the low-LFAT group. DISCUSSION: In
      obese women with previous gestational diabetes, LFAT, rather than any measure of
      body composition, is associated with features of insulin resistance.

PMID- 12226134
TI  - Visceral adipose tissue in women: longitudinal study of the effects of fat gain,
      time, and race.
AB  - OBJECTIVE: To determine the effects of fat gain, time, and race on the
      accumulation of visceral adipose tissue (VAT) in a group of normal-weight
      premenopausal women. RESEARCH METHODS AND PROCEDURES: Sixty-five women
      participated in the study (32 African American and 33 white). The mean age of
      subjects was 34 +/- 6 years (range, 22 to 47 years). Eligible subjects were women
      who had body mass indices <25 kg/m(2) at baseline and who had completed
      evaluations at baseline and at follow-up year 1, without intervention. A subset
      of subjects was reevaluated annually for up to 4 years. Body composition was
      assessed by DXA, and VAT was determined from a single computed tomography scan. A
      linear mixed model was used to examine changes in VAT over time, with total body
      fat as a covariate RESULTS: Total fat mass was not significantly different
      between races at baseline and increased significantly in both groups over time (p
      < 0.001). Time-related increases in total body fat were greater in African
      American women (p < 0.01). VAT was significantly higher in white women at
      baseline (p < 0.01) and increased significantly over time in both races (p <
      0.01), but remained higher in white women (p < 0.001). Increases in VAT, relative
      to total body fat, were greater than the increases in total body fat over time,
      independent of age and race (p < 0.001). DISCUSSION: Gaining total body-fat mass
      results in a higher increase in VAT, relative to total body fat, regardless of
      race and age, although African-American women maintain a lower VAT levels across
      time.

PMID- 12226135
TI  - Genetic and environmental influences on the tracking of body size from birth to
      early adulthood.
AB  - OBJECTIVE: This study identified genetic and environmental influences on the
      tracking of body size from birth to 16 to 18.5 years of age. RESEARCH METHODS AND
      PROCEDURES: Longitudinal information was collected from a nationally
      representative sample of Finnish twin adolescents (birth cohorts 1975 to 1979)
      and their parents through questionnaires mailed when the twins were ages 16 and
      18.5 years old. The sample included 702 monozygotic, 724 same-sex dizygotic, and
      762 opposite-sex dizygotic sets of twins. The measures used were length, weight,
      ponderal index (kilograms per cubic meters), and gestational age at birth, and
      height, weight, and body mass index (kilograms per square meters) at 16 to 18.5
      years of age. The changes in genetic and environmental influences on body size
      from birth to early adulthood were analyzed by quantitative genetic modeling.
      RESULTS: The twins who had a higher weight or ponderal index at birth were taller
      and heavier in early adulthood, whereas those who were longer at birth were
      taller, but not heavier, later in life. Adult height was affected more by the
      birth size than body mass index. In the genetic modeling analyses, the genetic
      factors accounting for the variation of body size became more apparent with age,
      and both genetic and environmental influences on stature had a sizable carry-over
      effect from birth to late adolescence, whereas for relative weight, the
      influences were more age-specific. DISCUSSION: The genetic and environmental
      architecture of body size changes from birth to adulthood. Even in monozygotic
      twins who share their genetic background, the initially larger twin tended to
      remain larger, demonstrating the long-lasting effects of fetal environment on
      final body size.

PMID- 12226136
TI  - Regional subcutaneous-fat loss induced by caloric restriction in obese women.
AB  - OBJECTIVE: With anthropometric models using skinfolds and circumferences, we
      studied changes in the percentage of subcutaneous fat in the total cross
      sectional area (SF%) at four body sites in obese women, before and after weight
      loss induced by 6 months of caloric restriction. RESEARCH METHODS AND PROCEDURES:
      In 61 obese women [31 African Americans and 30 whites; ages, 24 to 68 years; body
      mass index (BMI), > or =28 kg/m(2)], we measured SF% at the midpoint of the upper
      arm and thigh and the waistline and hipline, and we measured the percentage of
      total body fat by DXA before (Obs#1) and after (Obs#2) a 6-month nonintervention
      control period and then after 6 months on a 1200 kcal/d diet (Obs#3). RESULTS:
      The mean body weight and BMI increased (1.8 kg and 0.61 kg/m(2); p = 0.0001), but
      there were no significant changes in any other body composition measurements from
      Obs#1 to Obs#2. The means of Obs#3 for weight and BMI decreased by 11%, and the
      percentage of total body fat decreased by 13% of Obs#2 mean values (p = 0.0001).
      The mean SF% at each site decreased 7.6% to 18.0% of the Obs#2 mean values (p <
      0.001). The SF% decreases were greater at mid-arm and mid-thigh than in the cross
      sectional regions at the waistline and hipline (p = 0.05). There was no
      interaction between age or ethnicity (p > 0.2). CONCLUSIONS: In obese women,
      caloric restriction alone reduces anthropometrically measured subcutaneous fat
      proportionally more in peripheral than in central regions.

PMID- 12226137
TI  - Effect of smoking on the paradox of high waist-to-hip ratio and low body mass
      index.
AB  - OBJECTIVE: Research on diabetes mellitus (DM) indicates that people with a low
      body mass index (BMI) but a high waist-to-hip ratio (WHR) are in a particularly
      high-risk group. The purpose of this study was to investigate the prevalence of
      and the effect of smoking on this paradoxical relationship. RESEARCH METHODS AND
      PROCEDURES: Our study sample consisted of 3450 men and 4250 women who had
      participated in the Korean Nationwide Health Examination Survey. We divided the
      study sample into tertiles (low, medium, and high), according to the level of WHR
      and of BMI, which yielded nine different combinations. Individuals exhibiting so
      called paradox A had the highest WHR and the lowest BMI. RESULTS: The prevalence
      of paradox A was 4.7% for men and 3.8% for women. The overall agreement of WHR
      and BMI groups was poor [for men: kappa = 0.31 and 95% confidence interval (CI) =
      0.29 to 0.34; for women: kappa = 0.39 and 95% CI = 0.37 to 0.42 for women]. The
      odds ratios for subjects having paradox A were estimated using a logistic
      regression model after adjusting for age, age(2), height, education, smoking, use
      of alcohol, and exercise. The risk for paradox A among current smokers was 2.1
      fold (95% CI, 1.5 to 3.0) higher for men and 2.5-fold (95% CI, 1.6 to 3.9) higher
      for women than for nonsmokers, after adjusting for age and covariates.
      DISCUSSION: Cigarette smoking may increase the risk of paradox A. The findings of
      this study should be crossvalidated to different populations.

PMID- 12226138
TI  - Impact of weight-cycling history on bone density in obese women.
AB  - OBJECTIVE: The purpose of this study was to examine the effect of weight cycling
      (as defined by the frequency and magnitude of intentional weight loss) on bone
      mineral density and bone mineral content in obese sedentary women. RESEARCH
      METHODS AND PROCEDURES: Bone mineral content and density measured by DXA,
      submaximal physical fitness assessment, nutrient intake, oral contraceptive use,
      and weight-cycling history were assessed in 195 healthy, overweight sedentary
      women (age, 21 to 45 years; body mass index, 27 to 40 kg/m(2)) before beginning a
      behavioral weight-loss intervention. RESULTS: After controlling for body weight,
      multivitamin use, oral contraceptive/estrogen use, and calcium and magnesium
      intake, women who had a history of weight cycling did not have significantly
      lower total-body bone mineral content or density or total femur bone mineral
      density. In addition, 99% of subjects were above or within one SD of age and
      gender normative data for total femur bone mineral density. DISCUSSION: It does
      not seem that a history of weight cycling has an adverse affect on total femur
      and total-body bone mineral density in overweight sedentary premenopausal women.

PMID- 12226139
TI  - Lipid profile in the severely obese: changes with weight loss after lap-band
      surgery.
AB  - OBJECTIVE: To characterize dyslipidemia before and after weight loss in the
      severely obese. RESEARCH METHODS AND PROCEDURES: Five hundred fifteen subjects
      who had Lap-Band surgery were followed with yearly conventional lipid profiles
      for up to 4 years. Preoperative data were collected from the most recent 381
      subjects, and predictors of dyslipidemia were sought. One hundred seventy-one
      subjects completed a 1-year review, providing data to assess predictors of change
      in lipids. RESULTS: Favorable changes in fasting triglycerides (TG), high-density
      lipoprotein-cholesterol (HDL-C), and total cholesterol (TC):HDL-C ratio occurred
      within 1 year. All improvements were maintained up to 4 years. Male gender,
      central obesity, elevated fasting glucose, and insulin resistance were associated
      with less favorable lipid levels. Fasting plasma glucose best predicted TG (r =
      0.46, p < 0.001), whereas insulin sensitivity using the homeostatic model
      assessment (HOMA %S) correlated best with the HDL-C (r =0.34, p < 0.001). Higher
      preoperative fasting glucose best predicted the decrease in TG; improved HOMA %S
      with weight loss correlated best with HDL-C. The extent of weight loss had
      limited influence on lipid changes. However, low preoperative HOMA %S was
      associated with lower weight loss. Greater weight loss was associated with more
      favorable lipid measures after controlling for preoperative HOMA %S. DISCUSSION:
      Dyslipidemia of obesity is related to weight distribution, insulin sensitivity,
      and impaired glucose tolerance. Improvement with weight loss is related to the
      decrease in fasting glucose, improvement in insulin sensitivity, and the extent
      of weight lost. Improvement in dyslipidemia is sustained with long-term weight
      loss.

PMID- 12226140
TI  - An observational study of slimming behavior in Denmark in 1992 and 1998.
AB  - OBJECTIVE: To elucidate how frequent weight-loss attempts are made, the methods
      used to achieve weight loss, and the extent to which the outcome is positive.
      RESEARCH METHODS AND PROCEDURES: Two independent interviews were conducted in
      1992 and in 1998, each with 1200 randomly selected adult subjects. Each survey
      was designed to ensure an equal distribution of age, gender, and geographical
      regions in Denmark. RESULTS: The proportion of subjects having attempted weight
      loss did not change from 1992 to 1998, although the prevalence of overweight and
      obesity increased from 1992 (overweight, 30%; obesity, 6%) to 1998 (overweight,
      35%; obesity, 8%). Almost twice as many women (61%) than men (32%) had attempted
      weight loss (p < 0.0001). Slimming occurred more often in subjects <50 years
      (51%) than >50 years (39%) (p < 0.0001), although overweight and obesity were
      more frequent in the elderly. Over-the-counter diet pills or meal replacements
      were associated with a negative outcome of slimming treatment (p < 0.0001).
      DISCUSSION: Approximately half of all adult Danes have attempted weight loss,
      particularly women and individuals <50 years. This finding is inconsistent with
      the fact that overweight and obesity are more prevalent in men and in individuals
      >50 years. Changes in habitual diet and increased physical activity are the most
      prevalent modes of slimming, whereas the use of over-the-counter diet pills or
      meal replacements has decreased from 1992 to 1998. This development may have a
      positive impact on future body- weight-management strategies.

PMID- 12226141
TI  - Analysis of obesity and hyperinsulinemia in the development of metabolic
      syndrome: San Antonio Heart Study.
AB  - OBJECTIVE: To use standardized cut-offs of body mass index (BMI), waist
      circumference, waist-to-hip ratio, and fasting insulin levels to predict the
      development of metabolic disorders and metabolic syndrome. RESEARCH METHODS AND
      PROCEDURES: We performed an 8-year follow-up study of 628 non-Hispanic whites and
      1340 Mexican Americans, ages 25 to 64 years, from the second cohort of the San
      Antonio Heart Study. We defined metabolic disorders as dyslipidemia
      (triglycerides > or =2.26 mM or high-density lipoprotein <0.91 mM in men and
      <1.17 mM in women), hypertension (blood pressure > or =140 or >=90 mm Hg, or
      receiving antihypertensive medications), and type 2 diabetes (fasting glucose >
      or =7.0 mM, 2-hour test glucose > or =11.1 mM, or receiving anti-diabetic
      medications). People with at least two metabolic disorders were defined as having
      metabolic syndrome. RESULTS: High waist-to-hip ratio and fasting insulin levels
      were significant predictors of developing metabolic syndrome. High anthropometric
      indices remained significant predictors of metabolic syndrome after adjusting for
      fasting insulin. Waist circumference, BMI, and insulin had similar areas under
      the receiver operating characteristic curves (0.74 to 0.76). Further multivariate
      analyses combining these indices showed minimal increase in prediction. Of
      subjects who had a combination of high BMI (> or =30 kg/m(2)) and high waist
      circumference (above "Action Level 2"), 32% developed metabolic syndrome,
      compared with 10% of subjects with both low BMI and low waist circumference.
      DISCUSSION: These findings support the National Institutes of Health
      recommendations for reducing the risk of metabolic syndrome. Adjustment for
      baseline fasting insulin levels had only a small effect on the ability of
      anthropometric indices to predict the metabolic syndrome.

PMID- 12226142
TI  - Leptin production by the stomach is up-regulated in obese (fa/fa) Zucker rats.
AB  - OBJECTIVE: Genetically obese (fa/fa) Zucker rats display markedly elevated
      circulating leptin levels compared with their lean counterparts; this is expected
      because of the lack of a LepR-mediated feedback inhibition. The aim of this study
      was to determine the effect of the leptin receptor mutation in the Zucker rat on
      gastric leptin production and on the response to 14 hours of starvation. The
      response to a short-term period of food intake (20 minutes) on gastric leptin
      release was also analyzed. RESEARCH METHODS AND PROCEDURES: Leptin mRNA
      expression in the gastric mucosa and in adipose tissue depots (epididymal,
      retroperitoneal, mesenteric, and inguinal) was assessed by reverse transcriptase
      polymerase chain reaction and serum and stomach leptin content by enzyme-linked
      immunosorbent assay. RESULTS: Obese Zucker rats overexpressed leptin in the
      stomach. They overexpress leptin in the inguinal adipose tissue but not in
      visceral adipose tissue depots, indicating tissue-specific obesity-dependent
      differences. Gastric leptin expression is regulated by feeding conditions in lean
      but not in obese (fa/fa) rats. In lean animals, leptin mRNA levels decrease in
      fasting conditions and increase rapidly with a short period of food intake. Obese
      Zucker rats also overdisplay stomach leptin levels. Feeding acutely stimulates
      leptin secretion by the stomach in lean, and to a lesser extent, in obese rats.
      DISCUSSION: These results indicate impaired regulation of leptin expression in
      the stomach of obese (fa/fa) Zucker rats. However, there is still an effect of
      the nutritional status on gastric leptin levels despite the lack of a functional
      leptin receptor.

PMID- 12226143
TI  - Human leptin stimulates systemic nitric oxide production in the rat.
AB  - OBJECTIVE: Apart from having an effect on energy balance, leptin is also involved
      in cardiovascular regulation and in the pathogenesis of obesity-associated
      hypertension. We investigated the effect of leptin on nitric oxide (NO)
      production. RESEARCH METHODS AND PROCEDURES: Wistar rats were placed in metabolic
      cages, and urine was collected in 2-hour periods. After the control period,
      leptin (1 mg/kg intraperitoneal) was administered, and urine collection was
      continued for up to 6 hours. Blood was obtained 0.5, 1, 2, 4, and 6 hours after
      hormone injection. RESULTS: Leptin increased plasma concentrations of NO
      metabolites (nitrates + nitrites, NO(x)) by 32.5%, 58.0%, and 29.7% at 1, 2, and
      4 hours, respectively. Urinary NO(x) excretion increased by 28.8% in the first
      and by 20.1% in the second 2-hour period after injection. The plasma
      concentration of the NO second messenger, cyclic guanosine 3',5'-monophosphate
      (cGMP), increased by 83% and 50.6% at 2 and 4 hours after leptin administration,
      respectively. Urinary excretion of cyclic GMP increased by 36.1% in the first and
      by 43.1% in the second 2-hour period. Leptin had no effect on the plasma
      concentration of atrial natriuretic peptide (ANP). The effect of leptin on plasma
      and urinary NO(x) was abolished by the NO synthase inhibitor, N(G)-nitro-L
      arginine methyl ester (L-NAME) (30 mg/kg intraperitoneal) administered 15 minutes
      before leptin injection. L-NAME alone caused a 32.2% increase in systolic blood
      pressure, but this increase was not observed in rats receiving L-NAME and leptin.
      DISCUSSION: The results indicate that leptin stimulates systemic NO production;
      leptin prevents blood pressure elevation induced by acute NO blockade, suggesting
      that leptin also triggers additional hypotensive mechanisms; and ANP is not
      involved in renal and vascular effects of leptin.

PMID- 12226144
TI  - Effects of dietary fatty acids and exercise on body-weight regulation and
      metabolism in rats.
AB  - OBJECTIVE: To assess the interaction of high-fat diets (HF) made with different
      dietary fatty acids and exercise on body-weight regulation, adiposity, and
      metabolism. RESEARCH METHODS AND PROCEDURES: Male Wistar rats born to dams fed HF
      diets (40% w/w) made with either fish oil (FO), soybean oil (SO), or palm oil
      (PO) were fed diets similar to their dams and divided randomly into exercise (EX,
      swimming) or sedentary control (SD) groups when they were 9 weeks old. EX lasted
      for 6 weeks. Twenty-four hours after the last EX bout, fasted rats were killed by
      decapitation. Chemical analyses and body composition analysis were conducted.
      RESULTS: The results demonstrated that different fatty acids had different
      effects on body weight, composition, and metabolism. SO-fed rats gained the most
      weight and fat. EX reduced body weight of FO- and PO-fed rats, but SO-fed rats
      were still heavier and fatter than other rats. Data from SO- and PO-fed rats
      suggested that they are insulin resistant and that EX normalized this
      abnormality. Of the three HF diets used, FO produced the least adverse effects
      compared with PO and SO. DISCUSSION: Not only the quantity of dietary fat, but
      also the type of fat used, will produce different effects on body weight and
      metabolism. EX ameliorates the suggested insulin resistance induced in rats fed
      either highly saturated or n-6 polyunsaturated fatty acids. Long-chain n-3
      polyunsaturated fatty acids, as found in fish oil, are more beneficial than n-6
      polyunsaturated fatty acids when fed in high amounts to rats.

PMID- 12226145
TI  - Fat intake affects adiposity, comorbidity factors, and energy metabolism of
      sprague-dawley rats.
AB  - OBJECTIVE: Childhood obesity is an emerging health problem. This study assesses
      the effects of three levels of dietary fat (10%, 32%, and 45% measured by
      kilocalories) on weight gain, body composition, energy metabolism, and
      comorbidity factors in rats from weaning through maturation. RESEARCH METHODS AND
      PROCEDURES: The role of dietary fat on the susceptibility to obesity was assessed
      by feeding diets containing three levels of dietary fat to rats from weaning
      through 7 months of age. Body composition was analyzed by DXA after 6 and 12
      weeks of dietary treatment. Energy metabolism was measured by indirect
      calorimetry. RESULTS: Energy intake, weight gain, fat mass, and plasma glucose,
      cholesterol, triglyceride, free fatty acid, leptin, and insulin levels increased
      dose-dependently with increased dietary fat. No difference in absolute lean mass
      among the three groups was observed. Therefore, the differences in weight gain
      are accounted for primarily by increased fat accretion. Compared with rats that
      were relatively resistant to obesity when on a 45% fat diet, diet-induced obesity
      prone rats were in positive energy balance and had an elevated respiratory
      quotient, indicating a switch in energy substrate use from fat to carbohydrate,
      which promotes body-fat accretion. DISCUSSION: Our data support the hypothesis
      that administration of increasing amount of dietary fat to very young rats
      enhances susceptibility to diet-induced obesity and its comorbidities.

PMID- 12226146
TI  - Obesity, aerobic exercise, and vascular disease: the role of oxidant stress.
AB  - Oxidant formation in the vasculature contributes to vascular disease and
      dysfunction associated with obesity. In contrast, exercise-dependent production
      of oxidants may stimulate adaptive responses that protect against the development
      of such diseases. In this review, we discuss current concepts in the biology of
      reactive oxygen and nitrogen species and how their function is modulated in the
      context of vascular disease, obesity, and aerobic exercise.

PMID- 12226147
TI  - Ambulatory blood-pressure monitoring as a predictive tool.

PMID- 12226148
TI  - A randomized trial comparing radical prostatectomy with watchful waiting in early
      prostate cancer.
AB  - BACKGROUND: Radical prostatectomy is widely used in the treatment of early
      prostate cancer. The possible survival benefit of this treatment, however, is
      unclear. We conducted a randomized trial to address this question. METHODS: From
      October 1989 through February 1999, 695 men with newly diagnosed prostate cancer
      in International Union against Cancer clinical stage T1b, T1c, or T2 were
      randomly assigned to watchful waiting or radical prostatectomy. We achieved
      complete follow-up through the year 2000 with blinded evaluation of causes of
      death. The primary end point was death due to prostate cancer, and the secondary
      end points were overall mortality, metastasis-free survival, and local
      progression. RESULTS: During a median of 6.2 years of follow-up, 62 men in the
      watchful-waiting group and 53 in the radical-prostatectomy group died (P=0.31).
      Death due to prostate cancer occurred in 31 of 348 of those assigned to watchful
      waiting (8.9 percent) and in 16 of 347 of those assigned to radical prostatectomy
      (4.6 percent) (relative hazard, 0.50; 95 percent confidence interval, 0.27 to
      0.91; P=0.02). Death due to other causes occurred in 31 of 348 men in the
      watchful-waiting group (8.9 percent) and in 37 of 347 men in the radical
      prostatectomy group (10.6 percent). The men assigned to surgery had a lower
      relative risk of distant metastases than the men assigned to watchful waiting
      (relative hazard, 0.63; 95 percent confidence interval, 0.41 to 0.96).
      CONCLUSIONS: In this randomized trial, radical prostatectomy significantly
      reduced disease-specific mortality, but there was no significant difference
      between surgery and watchful waiting in terms of overall survival.

PMID- 12226149
TI  - Quality of life after radical prostatectomy or watchful waiting.
AB  - BACKGROUND: We evaluated symptoms and self-assessments of quality of life in men
      with localized prostate cancer who participated in a randomized comparison
      between radical prostatectomy and watchful waiting. METHODS: Between 1989 and
      1999, a group of Swedish urologists randomly assigned men with localized prostate
      cancer to radical prostatectomy or watchful waiting. In this follow-up study, we
      obtained information from 326 of 376 eligible men (87 percent) concerning certain
      symptoms, symptom-induced distress, well-being, and the subjective assessment of
      quality of life by means of a mailed questionnaire. RESULTS: Erectile dysfunction
      (80 percent vs. 45 percent) and urinary leakage (49 percent vs. 21 percent) were
      more common after radical prostatectomy, whereas urinary obstruction (e.g., 28
      percent vs. 44 percent for weak urinary stream) was less common. Bowel function,
      the prevalence of anxiety, the prevalence of depression, well-being, and the
      subjective quality of life were similar in the two groups. CONCLUSIONS: The
      assignment of patients to watchful waiting or radical prostatectomy entails
      different risks of erectile dysfunction, urinary leakage, and urinary
      obstruction, but on average, the choice has little if any influence on well-being
      or the subjective quality of life after a mean follow-up of four years.

PMID- 12226151
TI  - Cough and bronchial responsiveness in firefighters at the World Trade Center
      site.
AB  - BACKGROUND: Workers from the Fire Department of New York City were exposed to a
      variety of inhaled materials during and after the collapse of the World Trade
      Center. We evaluated clinical features in a series of 332 firefighters in whom
      severe cough developed after exposure and the prevalence and severity of
      bronchial hyperreactivity in firefighters without severe cough classified
      according to the level of exposure. METHODS: "World Trade Center cough" was
      defined as a persistent cough that developed after exposure to the site and was
      accompanied by respiratory symptoms severe enough to require medical leave for at
      least four weeks. Evaluation of exposed firefighters included completion of a
      standard questionnaire, spirometry, airway-responsiveness testing, and chest
      imaging. RESULTS: In the first six months after September 11, 2001, World Trade
      Center cough occurred in 128 of 1636 firefighters with a high level of exposure
      (8 percent), 187 of 6958 with a moderate level of exposure (3 percent), and 17 of
      1320 with a low level of exposure (1 percent). In addition, 95 percent had
      symptoms of dyspnea, 87 percent had gastroesophageal reflux disease, and 54
      percent had nasal congestion. Of those tested before treatment of World Trade
      Center cough, 63 percent of firefighters (149 of 237) had a response to a
      bronchodilator and 24 percent (9 of 37) had bronchial hyperreactivity. Chest
      radiographs were unchanged from precollapse findings in 319 of the 332 with World
      Trade Center cough. Among the cohort without severe cough, bronchial
      hyperreactivity was present in 77 firefighters with a high level of exposure (23
      percent) and 26 with a moderate level of exposure (8 percent). CONCLUSIONS:
      Intense, short-term exposure to materials generated during the collapse of the
      World Trade Center was associated with bronchial responsiveness and the
      development of cough. Clinical and physiological severity was related to the
      intensity of exposure.

PMID- 12226150
TI  - Increase in nocturnal blood pressure and progression to microalbuminuria in type
      1 diabetes.
AB  - BACKGROUND: Patients with type 1 diabetes mellitus and microalbuminuria often
      have elevated blood pressure while they are asleep, but it is not known whether
      the elevation develops concomitantly with microalbuminuria or precedes it.
      METHODS: We monitored 75 adolescents and young adults who had had type 1 diabetes
      with normal urinary albumin excretion and blood pressure for more than five
      years. Ambulatory blood-pressure monitoring was used to assess blood pressure at
      the initial evaluation and about two years later, at which time all subjects had
      normal urinary albumin excretion. Subsequently, subjects were monitored for the
      development of microalbuminuria. RESULTS: Microalbuminuria developed in 14
      subjects, whereas the other 61 continued to have normal urinary albumin
      excretion. The mean (+/-SD) systolic pressure during sleep increased
      significantly in the subjects who ultimately had microalbuminuria (from 109.9+/
      11.3 to 114.9+/-11.7 mm Hg, P=0.01) but not in the subjects with normal albumin
      excretion (from 106.0+/-8.8 to 106.4+/-14.8 mm Hg). The risk of progression to
      microalbuminuria was examined in relation to the ratio of systolic pressure
      during sleep to systolic pressure in the daytime. A ratio of 0.9 or lower, used
      to define a normal fall in nocturnal pressure, had a negative predictive value of
      91 percent for the development of microalbuminuria. Moreover, the risk of
      microalbuminuria was 70 percent lower (95 percent confidence interval, 44 to 110
      percent) in subjects with a ratio of 0.9 or less than in those with a ratio
      higher than 0.9 (P=0.01). CONCLUSIONS: In persons with type 1 diabetes, an
      increase in systolic blood pressure during sleep precedes the development of
      microalbuminuria. In those whose blood pressure during sleep decreases normally,
      the progression from normal albumin excretion to microalbuminuria appears to be
      less likely.

PMID- 12226152
TI  - Images in clinical medicine. Septic peripheral embolization from Haemophilus
      aphrophilus endocarditis.

PMID- 12226153
TI  - Clinical practice. Office-based treatment of opioid-dependent patients.

PMID- 12226154
TI  - Respiratory protection.

PMID- 12226155
TI  - Case records of the Massachusetts General Hospital. Weekly Clinicopathological
      exercises. Case 28-2002. A 35-year-old long-term traveler with a rapidly
      progressive soft-tissue infection.

PMID- 12226156
TI  - Surgery and the reduction of mortality from prostate cancer.

PMID- 12226157
TI  - World Trade Center cough--a lingering legacy and a cautionary tale.

PMID- 12226158
TI  - Restoring the addicted brain.

PMID- 12226159
TI  - Switching emergency contraception to over-the-counter status.

PMID- 12226160
TI  - Pulmonary dead space and survival.

PMID- 12226161
TI  - Neuroblastoma screening in early life.

PMID- 12226162
TI  - Germ-line mutations in nonsyndromic pheochromocytoma.

PMID- 12226163
TI  - Case 9-2002: orbital mucormycosis.

PMID- 12226164
TI  - Bioterrorism and civil liberties.

PMID- 12226165
TI  - Hyperosmolar metabolic acidosis and intravenous Lorazepam.

PMID- 12226166
TI  - Medical mystery--the answer.

PMID- 12226167
TI  - Gastrointestinal angiodysplasia and aortic stenosis.

PMID- 12226168
TI  - The Cyanide-Resistant Oxidase: To Inhibit or Not to Inhibit, That Is the
      Question.

PMID- 12226169
TI  - Variation in Lignin Content and Composition (Mechanisms of Control and
      Implications for the Genetic Improvement of Plants).

PMID- 12226170
TI  - Nuclear Matrix Attachment Regions and Transgene Expression in Plants.

PMID- 12226171
TI  - Photosystem II Excitation Pressure and Development of Resistance to
      Photoinhibition (II. Adjustment of Photosynthetic Capacity in Winter Wheat and
      Winter Rye).
AB  - Winter wheat (Triticum aestivum L. cv Monopol), spring wheat (Triticum aestivum
      L. cv Katepwa), and winter rye (Secale cereale L. cv Musketeer) grown at 5[deg]C
      and moderate irradiance (250 [mu]mol m-2 s-1) (5/250) exhibit an increased
      tolerance to photoinhibition at low temperature in comparison to plants grown at
      20[deg]C and 250 [mu]mol m-2 s-1 (20/250). However, 5/250 plants exhibited a
      higher photosystem II (PSII) excitation pressure (0.32-0.63) than 20/250 plants
      (0.18-0.21), measured as 1 - qP, the coefficient of photochemical quenching.
      Plants grown at 20[deg]C and a high irradiance (800 [mu]mol m-2 s-1) (20/800)
      also exhibited a high PSII excitation pressure (0.32-0.48). Similarly, plants
      grown at 20/800 exhibited a comparable tolerance to photoinhibition relative to
      plants grown at 5/250. In contrast to a recent report for Chlorella vulgaris
      (D.P. Maxwell, S. Falk, N.P.A. Huner [1995] Plant Physiol 107: 687-694), this
      tolerance to photoinhibition occurs in winter rye with minimal adjustment to
      polypeptides of the PSII light-harvesting complex, chlorophyll a/b ratios, or
      xanthophyll cycle carotenoids. However, Monopol winter wheat exhibited a 2.5-fold
      stimulation of sucrosephosphate synthase activity upon growth at 5/250, in
      comparison to Katepwa spring wheat. We demonstrate that low-temperature-induced
      tolerance to photoinhibition is not a low-temperature-growth effect per se but,
      instead, reflects increased photosynthetic capacity in response to elevated PSII
      excitation pressure, which may be modulated by either temperature or irradiance.

PMID- 12226172
TI  - Coordinated Regulation of the Genes Participating in Starch Biosynthesis by the
      Rice Floury-2 Locus.
AB  - The recessive floury-2 (flo-2) locus of rice (Oryza sativa L.), which is located
      on chromosome 4, causes a strong reduction in expression of the gene encoding an
      isoform of branching enzyme RBE1 in immature seeds 10 d after flowering. Mapping
      of the RBE1 gene demonstrated the localization on rice chromosome 6, suggesting
      that the wild-type Floury-2 (Flo-2) gene regulates RBE1 gene expression in trans.
      However, reduced expression of the genes encoding some other starch-synthesizing
      enzymes, including another isoform of branching enzyme RBE3 and granule-bound
      starch synthase, was also found in the flo-2 seeds. In spite of the low level of
      RBE1 gene expression in the immature seeds of the flo-2 mutants, the RBE1 gene
      was equally expressed in the leaves of the wild type and flo-2 mutants. Thus,
      these results imply that the Flo-2 gene may co-regulate expression of some of the
      genes participating in starch synthesis possibly in a developing seed-specific
      manner.

PMID- 12226174
TI  - The Fungicide Phosphonate Disrupts the Phosphate-Starvation Response in Brassica
      nigra Seedlings.
AB  - The development of Brassica nigra seedlings over 20 d of growth was disrupted by
      the fungicide phosphonate (Phi) in a manner inversely correlated with nutritional
      inorganic phosphate (Pi) levels. The growth of Pi-sufficient (1.25 mM Pi)
      seedlings was suppressed when 10, but not 5, mM Phi was added to the nutrient
      medium. In contrast, the fresh weights and root:shoot ratios of Pi-limited (0.15
      mM) seedlings were significantly reduced at 1.5 mM Phi, and they progressively
      declined to about 40% of control values as medium Phi concentration was increased
      to 10 mM. Intracellular Pi levels generally decreased in Phi-treated seedlings,
      and Phi accumulated in leaves and roots to levels up to 6- and 16-fold that of Pi
      in Pi-sufficient and Pi-limited plants, respectively. Extractable activities of
      the Pi-starvation-inducible enzymes phosphoenolpyruvate phosphatase and inorganic
      pyrophosphate-dependent phosphofructokinase were unaltered in Pi-sufficient
      seedlings grown on 5 or 10 mM Phi. However, when Pi-limited seedlings were grown
      on 1.5 to 10 mM Phi (a) the induction of phosphoenolpyruvate phosphatase and
      inorganic pyrophosphate-dependent phosphofructokinase activities by Pi limitation
      was reduced by 40 to 90%, whereas (b) soluble protein concentrations and the
      activities of the ATP-dependent phosphofructokinase and pyruvate kinase were
      unaffacted. It is concluded that Phi specifically interrupts processes involved
      in regulation of the Pi-starvation response in B. nigra.

PMID- 12226173
TI  - The Kinetics of N-Ethylmaleimide Inhibition of a Vacuolar H+-ATPase and
      Determination of Nucleotide Dissociation Constants.
AB  - All eukaryotic vacuolar (V-type) ATPases share the property of being inhibited by
      low concentrations (1-2 [mu]M) if N-ethylmaleimide (NEM). This distinguishes them
      from P-type ATPases, which are inhibited by higher concentrations of NEM (0.1-1
      mM), and F-type ATPases, which are virtually resistant to inhibition by NEM.
      Using tonoplast vesicles from Beta vulgaris we have determined the kinetics of
      NEM inactivation of the V-type ATPase to be pseudo-first order. The concentration
      dependence of the reaction indicates interaction with a single class of
      inhibitory site with a rate constant of 4.1 x 104 M-1 min-1. Nucleotides protect
      against inactivation with an efficacy that agrees with their capacity to act as
      enzyme substrates. The dissociation constant for MgATP has been determined from
      protection experiments to be 0.44 mM, which is close to the observed Km for
      hydrolysis (0.39 mM). Likewise, the dissociation constant for protection by MgADP
      (127 [mu]M) is close to its inhibition constant as a competitive inhibitor (110
      [mu]M). Taken together, these findings suggest that NEM inactivation is
      associated with nucleotide protectable exposure of a single cysteine residue on
      the catalytic subunit and confirm the utility of this residue for the
      determination of ligand dissociation constants through protection of maleimide
      inhibition.

PMID- 12226175
TI  - The pH Requirement for in Vivo Activity of the Iron-Deficiency-Induced "Turbo"
      Ferric Chelate Reductase (A Comparison of the Iron-Deficiency-Induced Iron
      Reductase Activities of Intact Plants and Isolated Plasma Membrane Fractions in
      Sugar Beet).
AB  - The characteristics of the Fe reduction mechanisms induced by Fe deficiency have
      been studied in intact plants of Beta vulgaris and in purified plasma membrane
      vesicles from the same plants. In Fe-deficient plants the in vivo Fe(III)
      ethylenediaminetetraacetic complex [Fe(III)-EDTA] reductase activity increased
      over the control values 10 to 20 times when assayed at a pH of 6.0 or below
      ("turbo" reductase) but increased only 2 to 4 times when assayed at a pH of 6.5
      or above. The Fe(III)-EDTA reductase activity of root plasma membrane
      preparations increased 2 and 3.5 times over the controls, irrespective of the
      assay pH. The Km for Fe(III)-EDTA of the in vivo ferric chelate reductase in Fe
      deficient plants was approximately 510 and 240 [mu]M in the pH ranges 4.5 to 6.0
      and 6.5 to 8.0, respectively. The Km for Fe(III)-EDTA of the ferric chelate
      reductase in intact control plants and in plasma membrane preparations isolated
      from Fe-deficient and control plants was approximately 200 to 240 [mu]M.
      Therefore, the turbo ferric chelate reductase activity of Fe-deficient plants at
      low pH appears to be different from the constitutive ferric chelate reductase.

PMID- 12226176
TI  - The Complexity of Enzymic Control of Hydrogen Peroxide Concentration May Affect
      the Regeneration Potential of Plant Protoplasts.
AB  - Total peroxidase, NADH-peroxidase, ascorbate peroxidase, superoxide dismutase,
      and catalase activities were measured in tobacco (Nicotiana tabacum) leaves and
      in regenerating and nonregenerating protoplasts isolated from the same tissue and
      cultured for 2 weeks. The specific ranges of H2O2 concentration at which the
      enzymes scavenging the active forms of oxygen may efficiently operate and the
      activities of those enzymes were determined in an extract from tobacco leaves and
      in dividing and nondividing tobacco mesophyll protoplasts. The overall H2O2
      scavenging enzyme activities were similar in both protoplast populations during
      the 2 to 3 d of culture. After 3 d, the regenerating protoplasts started to
      divide and both the antioxidant enzyme activities and the total peroxidase
      activity increased; in contrast, the viability and the H2O2-scavenging enzyme
      activities in nonregenerating protoplasts dramatically decreased. Surprisingly,
      the regenerative potentiality in dividing protoplasts was specifically correlated
      with a higher NADH-peroxidase activity, which resulted in a net H2O2 accumulation
      in the cells. Light, which causes the accumulation of active forms of oxygen in
      photosynthetic organelles, also stimulated catalase and ascorbate peroxidase
      activities in dividing protoplasts. We suggest that the localization of H2O2
      rather than its absolute concentration might be responsible for oxidative stress
      and that controlled amounts of H2O2 are necessary to allow proper cell-wall
      reconstitution and the consequent cell division.

PMID- 12226177
TI  - Biochemistry of Short-Chain Alkanes (Tissue-Specific Biosynthesis of n-Heptane in
      Pinus jeffreyi).
AB  - Short-chain (C7-C11) alkanes accumulate as the volatile component of oleoresin
      (pitch) in several pine species native to western North America. To establish the
      tissue most amenable for use in detailed studies of short-chain alkane
      biosynthesis, we examined the tissue specificity of alkane accumulation and
      biosynthesis in Pinus jeffreyi Grev. & Balf. Short-chain alkane accumulation was
      highly tissue specific in both 2-year-old saplings and mature trees; heart-wood
      xylem accumulated alkanes up to 7.1 mg g-1 dry weight, whereas needles and other
      young green tissue contained oleoresin with monoterpenoid, rather than
      paraffinic, volatiles. These tissue-specific differences in oleoresin composition
      appear to be a result of tissue-specific rates of alkane and monoterpene
      biosynthesis; incubation of xylem tissue with [14C]sucrose resulted in
      accumulation of radiolabel in alkanes but not monoterpenes, whereas incubation of
      foliar tissue with 14CO2 resulted in the accumulation of radiolabel in
      monoterpenes but not alkanes. Furthermore, incubation of xylem sections with
      [14C]acetate resulted in incorporation of radiolabel into alkanes at rates up to
      1.7 nmol h-1 g-1 fresh weight, a rate that exceeds most biosynthetic rates
      reported with other plant systems for the incorporation of this basic precursor
      into natural products. This suggests that P. jeffreyi may provide a suitable
      model for elucidating the enzymology and molecular biology of short-chain alkane
      biosynthesis.

PMID- 12226178
TI  - In Vitro Cyclic Electron Transport in Barley Thylakoids follows Two Independent
      Pathways.
AB  - In vitro cyclic electron transport around PSI was studied in thylakoids isolated
      from barley (Hordeum vulgare L.). Redox poising was obtained by using anaerobic
      conditions, preillumination, and the addition of 3-(3,4-dichlorophenyl)-1,1
      dimethylurea. Postillumination rates of P700+ re-reduction of 1 to 5 electrons s
      1 were observed, depending on the conditions. The thylakoids supported two
      parallel paths of cyclic electron transport that were distinguishable by
      differences in antimycin sensitivity, saturation characteristics, and substrate
      specificity. The pathway most sensitive to antimycin was not saturated at
      ferredoxin concentrations up to 50 [mu]M, whereas the more insensitive pathway
      was saturated at 5 [mu]M ferredoxin. At the lower concentration of reduced
      ferredoxin, the antimycin-sensitive rate of P700+ re-reduction was lower than the
      antimycin-insensitive rate. The lower range of reduced ferredoxin concentrations
      are closer to in vivo conditions. Flavodoxin is shown to mediate cyclic electron
      transport. Flavodoxin was less efficient in mediating the antimycin-sensitive
      pathway but mediated the antimycin-insensitive pathway as efficiently as
      ferredoxin. Antibodies raised against ferredoxin:NADP+ oxidoreductase had no
      effect on either pathway for re-reduction of P700+. However, the ferredoxin:
      NADP+ oxidoreductase inhibitor 2[prime]-monophosphoadenosine-5[prime]
      diphosphoribose was able to inhibit the antimycin-sensitive as well as the
      antimycin-insensitive pathway.

PMID- 12226179
TI  - Formation of Root Epidermal Transfer Cells in Plantago.
AB  - The root ultrastructure and transmembrane electron transport activities of two
      Plantago species have been examined with respect to alterations in response to Fe
      deficiency, exogenously supplied auxin, and the presence of chromium in the
      external medium. Both species showed increased ferric reductase activity upon Fe
      starvation, but they differed in the maximum rates. The addition of chromium to
      the nutrient solution led to a further enhancement in Fe
      ethylenediaminetetraacetate reduction by Fe-deficient plants. In roots of
      Plantago lanceolata, the enhanced redox activity is associated with the formation
      of transfer cells in the epidermis. Similar characteristics of rhizodermal cells
      were observed in Fe-sufficient roots 3 d after application of the auxin analog
      2,4-dichlorophenoxy-acetic acid. No structural adaptations occurred in roots of
      Plantago maritima. A quantitative estimation of the frequencies of transfer cells
      in root segments of Fe-deficient plants that differ in reduction activity
      revealed no correlation between the two phenomena. It is concluded that the area
      of plasmalemma infoldings is not specialized for the enhanced reduction of
      extracytoplasmatic Fe in response to Fe deficiency. The role of transfer cells in
      the adaptation to suboptimal Fe availability and the mechanisms triggering their
      formation are discussed.

PMID- 12226180
TI  - Induction and Regulation of Heat-Shock Gene Expression by an Amino Acid Analog in
      Soybean Seedlings.
AB  - The effect of the proline analog azetidine-2-carboxylic acid (Aze) on the
      induction and the regulation of heat-shock (HS) mRNA accumulation and heat-shock
      protein (HSP) synthesis in soybean (Glycine max) seedlings was studied. Treatment
      with Aze elicited an HS-like response at the normal growth temperature, 28[deg]C,
      with seven of nine HS cDNA clones tested. Two cDNA clones, Gm-Hsp22.5 and
      pFS2033, share 78% identity; however, transcripts hybridizing to GmHsp22.5 but
      not pFS2033 accumulated with Aze treatment at 28[deg]C. Substantial incorporation
      of radioactive amino acid into high molecular weight HSPs but not low molecular
      weight HSPs was observed in vivo during Aze treatment at 28[deg]C. Low molecular
      weight HSPs were detected using antibodies raised against an abundant member of
      low molecular weight class I HSPs, indicating that low molecular weight HSPs were
      synthesized at normal growth temperatures during Aze treatment despite a lack of
      substantial in vivo radioactive amino acid incorporation. In summary, Aze
      treatment induced accumulation of most but not all HS mRNAs and HSPs in soybean
      seedlings; the observations presented here suggest differential regulation among
      various HS genes at the transcriptional and posttranscriptional levels.

PMID- 12226181
TI  - Expression of a Late Embryogenesis Abundant Protein Gene, HVA1, from Barley
      Confers Tolerance to Water Deficit and Salt Stress in Transgenic Rice.
AB  - A late embryogenesis abundant (LEA) protein gene, HVA1, from barley (Hordeum
      vulgare L.) was introduced into rice suspension cells using the Biolistic
      mediated transformation method, and a large number of independent transgenic rice
      (Oryza sativa L.) plants were generated. Expression of the barley HVA1 gene
      regulated by the rice actin 1 gene promoter led to high-level, constitutive
      accumulation of the HVA1 protein in both leaves and roots of transgenic rice
      plants. Second-generation transgenic rice plants showed significantly increased
      tolerance to water deficit and salinity. Transgenic rice plants maintained higher
      growth rates than nontransformed control plants under stress conditions. The
      increased tolerance was also reflected by delayed development of damage symptoms
      caused by stress and by improved recovery upon the removal of stress conditions.
      We also found that the extent of increased stress tolerance correlated with the
      level of the HVA1 protein accumulated in the transgenic rice plants. Using a
      transgenic approach, this study provides direct evidence supporting the
      hypothesis that LEA proteins play an important role in the protection of plants
      under water-or salt-stress conditions. Thus, LEA genes hold considerable
      potential for use as molecular tools for genetic crop improvement toward stress
      tolerance.

PMID- 12226182
TI  - Influence of Environmental Factors and Air Composition on the Emission of [alpha]
      Pinene from Quercus ilex Leaves.
AB  - We studied the emission of [alpha]-pinene from Quercus ilex leaves. Only the
      abaxial side of the hypostomatous Q. ilex leaf emits [alpha]-pinene. Light
      induced photosynthesis and [alpha]-pinene emission. However, the response of
      photosynthesis to dark-to-light transitions was faster than that of [alpha]
      pinene, suggesting that ATP controls the emission. The emission was higher at 30
      than at 20[deg]C, whereas photosynthesis did not change. Therefore, the
      relationship between photosynthesis and [alpha]-pinene emission does not always
      hold. When CO2 was removed from the air, transpiration was stimulated but
      photosynthesis and [alpha]-pinene emission were inhibited. [alpha]-Pinene
      inhibition was more rapid under low O2. When CO2 in the air was increased,
      photosynthesis was stimulated and transpiration was reduced, but [alpha]-pinene
      emission was unaffected. Therefore, the emission depends on the availability of
      photosynthetic carbon, is not saturated at ambient CO2, and is not dependent on
      stomatal opening. The pattern of [alpha]-pinene emission from Q. ilex is
      different from that of plants having specialized structures for storage and
      emission of terpenes. We suggest that [alpha]-pinene emitted by Q. ilex leaves is
      synthesized in the chloroplasts and shares the same biochemical pathway with
      isoprene emitted by isoprene-emitting oak species.

PMID- 12226183
TI  - Photosynthesis in Salt-Adapted Heterotrophic Tobacco Cells and Regenerated
      Plants.
AB  - Tobacco (Nicotiana tabacum L.) cells growing heterotrophically in the light on
      supplied sucrose (S0) have previously been adapted to grow in 428 mM NaCl (S25).
      Among the changes occurring in salinity-adapted cell cultures are (a) elevated
      levels of chlorophyll compared to unadapted cells; (b) decreased levels of
      starch; (c) alterations in chloroplast ultrastructure, including loss of starch
      grains, increased thylakoid membrane structure, and the presence of
      plastoglobules; and (d) increased rates of O2 evolution, CO2 fixation, and
      photophosphorylation relative to S0 cells. These latter changes apparently derive
      from the fact that thylakoid membranes in S25 cells contain higher levels of
      photosystem I- and II-associated proteins as well as thylakoid ATPase components.
      S25 chloroplasts contain immunologically detectable levels of ribulose-1,5
      bisphosphate carboxylase/oxygenase, whereas S0 completely lack the enzyme. These
      changes taken together suggest that even in the presence of sucrose, S25 cells
      have acquired a significant degree of salt-tolerant photosynthetic competence.
      This salt-tolerant photoysynthetic capability manifests itself in plants
      backcrossed with normal plants for three generations. These plants contain
      chloroplasts that demonstrate in vitro more salt-tolerant CO2 fixation, O2
      evolution, and photophosphorylation than do backcross progeny of plants
      regenerated from S0 cultures.

PMID- 12226184
TI  - Shoot-to-Root Signal Transmission Regulates Root Fe(III) Reductase Activity in
      the dgl Mutant of Pea.
AB  - To understand the root, shoot, and Fe-nutritional factors that regulate root Fe
      acquisition processes in dicotyledonous plants, Fe(III) reduction and net proton
      efflux were quantified in root systems of an Fe-hyperaccumulating mutant (dgl)
      and a parental (cv Dippes Gelbe Viktoria [DGV]) genotype of pea (Pisum sativum).
      Plants were grown with (+Fe treated) or without (-Fe treated) added Fe(III)-N,N'
      ethylenebis[2-(2-hydroxyphenyl)-glycine] (2 [mu]M); root Fe(III) reduction was
      measured in solutions containing growth nutrients, 0.1 mM Fe(III)
      ethylenediaminetetraacetic acid, and 0.1 mM Na2-bathophenanthrolinedisulfonic
      acid. Daily measurements of Fe(III) reduction (d 10-20) revealed initially low
      rates in +Fe-treated and -Fe-treated dgl, followed by a nearly 5-fold stimulation
      in rates by d 15 for both growth types. In DGV, root Fe(III) reductase activity
      increased only minimally by d 20 in +Fe-treated plants and about 3-fold in -Fe
      treated plants, beginning on d 15. Net proton efflux was enhanced in roots of -Fe
      treated DGV and both dgl growth types, relative to +Fe-treated DGV. In dgl, the
      enhanced proton efflux occurred prior to the increase in root Fe(III) reductase
      activity. Reductase studies using plants with reciprocal shoot:root grafts
      demonstrated that shoot expression of the dgl gene leads to the generation of a
      transmissible signal that enhances Fe(III) reductase activity in roots. The dgl
      gene product may alter or interfere with a normal component of a signal
      transduction mechanism regulating Fe homeostasis in plants.

PMID- 12226185
TI  - Carbon Dioxide Diffusion inside Leaves.

PMID- 12226186
TI  - Competence for Elicitation of H2O2 in Hypocotyls of Cucumber Is Induced by
      Breaching the Cuticle and Is Enhanced by Salicylic Acid.
AB  - To study H2O2 production, the epidermal surfaces of hypocotyl segments from
      etiolated seedlings of cucumber (Cucumis sativus L.) were gently abraded. Freshly
      abraded segments were not constitutively competent for rapid H2O2 elicitation.
      This capacity developed subsequent to abrasion in a time-dependent process that
      was greatly enhanced in segments exhibiting an acquired resistance to penetration
      of their epidermal cell walls by Colletotrichum lagenarium, because of root
      pretreatment of the respective seedlings with 2,6-dichloroisonicotinic acid. When
      this compound or salicylic acid was applied to abraded segments, it also greatly
      enhanced the induction of competence for H2O2 elicitation. This process was fully
      inhibited by 5 [mu]M cycloheximide or 200 [mu]M puromycin, suggesting a
      requirement for translational protein synthesis. Both a crude elicitor
      preparation and a partially purified oligoglucan mixture from Phytophthora sojae
      also induced, in addition to H2O2 production, a refractory state, which explains
      the transient nature of H2O2 elicitation. Taken together, these results suggest
      that the cucumber hypocotyl epidermis becomes conditioned for competence to
      produce H2O2 in response to elicitors by a stimulus resulting from breaching the
      cuticle and/or cutting segments. This conditioning process is associated with
      protein synthesis and is greatly enhanced when substances able to induce systemic
      acquired resistance are present in the tissue.

PMID- 12226187
TI  - Fructan Accumulation and Sucrose Metabolism in Transgenic Maize Endosperm
      Expressing a Bacillus amyloliquefaciens SacB Gene.
AB  - Over 40,000 species of plants accumulate fructan, [beta]-2-1- and [beta]-2-6
      linked polymers of fructose as a storage reserve. Due to their high fructose
      content, several commercial applications for fructans have been proposed.
      However, plants that accumulate these polymers are not agronomically suited for
      large-scale cultivation or processing. This study describes the transformation of
      a Bacillus amyloliquefaciens SacB gene into maize (Zea mays L.) callus by
      particle bombardment. Tissue-specific expression and targeting of the SacB
      protein to endosperm vacuoles resulted in stable accumulation of high-molecular
      weight fructan in mature seeds. Accumulation of fructan in the vacuole had no
      detectable effect on kernel development or germination. Fructan levels were found
      to be approximately 9-fold higher in sh2 mutants compared to wild-type maize
      kernels. In contrast to vacuole-targeted expression, starch synthesis and
      endosperm development in mature seeds containing a cytosolically expressed SacB
      gene were severely affected. The data demonstrate that hexose resulting from
      cytosolic SacB activity was not utilized for starch synthesis. Transgenic seeds
      containing a chimeric SacB gene provide further evidence that the dominant
      pathway for starch synthesis in maize endosperm is through uridine
      diphosphoglucose catalyzed by the enzyme sucrose synthase.

PMID- 12226188
TI  - Physiological and Molecular Characteristics of Elicitin-Induced Systemic Acquired
      Resistance in Tobacco.
AB  - Elicitins are low molecular weight proteins secreted by all Phytophthora species
      analyzed so far. Application of the purified proteins to tobacco Nicotiana
      tabacum leads to the induction of resistance to subsequent inoculations with the
      black shank-causing agent, Phytophthora parasitica var nicotianae. In this paper,
      we describe the systemic characteristics of elicitin-induced acquired resistance
      in tobacco. Elicitin application is followed by the rapid translocation of the
      protein in the plant. The basic elicitin, cryptogein, induces necrosis formation
      in the leaves, which results from accumulation of the protein in these organs.
      Necrosis does not seem to be essential for the establishment of systemic acquired
      resistance (SAR), since resistance induced by the acidic elicitin, capsicein, is
      not accompanied by the development of visible symptoms on the leaves. Both
      elicitins trigger the coordinate accumulation of transcripts from nine genes,
      previously described to be expressed during establishment of SAR. Additionally,
      elicitin treatment leads to the activation of the multiple response gene str 246.
      In leaves, transcript accumulation was found to be higher in all cases in
      response to cryptogein compared to capsicein treatment. These results, along with
      northern hybridization analysis following infiltration of leaves with cryptogein,
      indicate that SAR genes appear to be expressed locally, corresponding to necrosis
      formation as well as systemically during induction of resistance. To our
      knowledge, elicitins are the only well-characterized, pathogen-derived molecules
      that trigger SAR in a plant.

PMID- 12226189
TI  - Mutants in Arabidopsis thaliana Altered in Epicuticular Wax and Leaf Morphology.
AB  - We report eight new mutants in Arabidopsis thaliana possessing altered leaf
      morphology and epicuticular wax. These were isolated from a T-DNA-mutagenized
      population using a visual screen for altered leaf reflectance, i.e. increased
      glaucousness or glossiness. The mutants were placed into three distinct classes
      based on alterations in overall plant morphology: knobhead (knb), bicentifolia
      (bcf), and wax. The four knb mutants formed callus-like growths in the axillary
      region of the rosette leaves and apical meristem, the two bcf mutants produced
      hundreds of narrow leaves, and the two wax mutants had leaves and stems that were
      more glossy than wild type and organs that fused during early development. Leaves
      of knb and bcf were more glaucous and abnormally shaped than wild type.
      Epicuticular wax crystals over knb and bcf leaf surfaces (where none were present
      on wild type) likely contributed to their more glaucous appearance. In contrast,
      the glossy appearance of the wax mutants was associated with a reduced
      epicuticular wax load on both leaves and stems. One representative from each
      phenotypic class was selected for detailed analyses of epicuticular wax
      chemistry. All three lines, knb1, bcf1, and wax1, had dramatic alterations in the
      total amounts and relative proportions of their leaf epicuticular wax
      constituents.

PMID- 12226190
TI  - Involvement of Jasmonic Acid in Elicitor-Induced Phytoalexin Production in
      Suspension-Cultured Rice Cells.
AB  - It has been suggested that jasmonic acid (JA) could be an integral part of a
      general signal transduction system regulating inducible defense genes in plants.
      It was reported that treatment with an elicitor (N-acetylchitoheptaose) induced
      production of phytoalexin in suspension-cultured rice (Oryza sativa L.) cells. In
      this study, the role of JA in the induction of phytoalexin production by N
      acetylchitoheptaose was investigated. Exogenously applied ([plus or minus])-JA
      (10-4 M) clearly induced the production of momilactone A, a major phytoalexin, in
      suspension-cultured rice cells. On the other hand, in rice cells treated with N
      acetylchitoheptaose, endogenous JA was rapidly and transiently accumulated prior
      to accumulation of momilactone A. Treatment with ibuprofen, an inhibitor of JA
      biosynthesis, reduced production of momilactone A in the cells treated with N
      acetylchitoheptaose, but the addition of ([plus or minus])-JA increased
      production of momilactone A to levels higher than those in the elicited rice
      cells. These results strongly suggest that JA functions as a signal transducer in
      the induction of biosynthesis of momilactone A by N-acetylchitoheptaose in
      suspension-cultured rice cells.

PMID- 12226191
TI  - Responses of Antioxidative Systems to Drought Stress in Pendunculate Oak and
      Maritime Pine as Modulated by Elevated CO2.
AB  - The aim of the present study was to investigate the effects of an enhanced CO2
      concentration alone or in combination with drought stress on antioxidative
      systems of a deciduous (oak; Quercus robur) and an evergreen (pine; Pinus
      pinaster) tree species. The seedlings were grown for one season in a greenhouse
      in tunnels supplied with 350 or 700 [mu]L L-1 CO2. The experiment was repeated in
      a second year. Antioxidants, protective enzymes, soluble protein, and pigments
      showed considerable fluctuations in different years. Elevated CO2 caused
      significant reductions in the activities of superoxide dismutases in both oak and
      pine. The activities of ascorbate peroxidase and catalase were also reduced in
      most cases. The activities of dehydroascorbate reductase, monodehydroascorbate
      radical reductase, glutathione reductase, and guaiacol peroxidase were affected
      little or not at all by elevated CO2. When the trees were subjected to drought
      stress by withholding water, the activities of antioxidative enzymes decreased in
      leaves of pine and oak grown at ambient CO2 and increased in plants grown at
      elevated CO2 concentrations. The present results suggest that growth in elevated
      CO2 might reduce oxidative stress to which leaf tissues are normally exposed and
      enhance metabolic flexibility to encounter increased stress by increases in
      antioxidative capacity.

PMID- 12226192
TI  - Changing the Dimensions of Suberin Lamellae of Green Cotton Fibers with a
      Specific Inhibitor of the Endoplasmic Reticulum-Associated Fatty Acid Elongases.
AB  - The fibers of the green lint mutant of cotton (Gossypium hirsutum L.) contain
      large amounts of wax and are suberized. More than 96% of the bifunctional
      aliphatic suberin monomers ([alpha],[omega]-alkanedioic acids and [omega]
      hydroxyalkanoic acids) have chain lengths of C22 and C24 in green cotton fiber
      suberin. In fibers grown in the presence of S-ethyl-N,N-dipropylthiocarbamate
      (EPTC), a specific inhibitor of the endoplasmic reticulum-associated fatty acid
      elongases, the aliphatic suberin monomers were shortened to chain lengths of C16
      and C18. Whereas the amounts of most suberin monomers were not negatively
      affected by the inhibitor treatment, the amounts of [alpha],[omega]-alkanedioic
      acids and of glycerol were reduced by more than 80%. Analysis in the transmission
      electron microscope showed a reduction in suberin content after EPTC treatment.
      The suberin layers were discontinuous and consisted of fewer lamellae than in the
      controls. A small proportion (up to 22%) of the electron-translucent suberin
      lamellae were thinner after EPTC treatment, probably because of the shortening of
      the aliphatic suberin monomers. A larger proportion of the electron-translucent
      lamellae were thicker than the lamellae in the controls. Possible explanations
      for this observation are discussed.

PMID- 12226193
TI  - Gibberellin Metabolism in Maize (The Stepwise Conversion of Gibberellin A12
      Aldehyde to Gibberellin A20.
AB  - The stepwise metabolism of gibberellin A12-aldehyde (GA12-aldehyde) to GA20 is
      demonstrated from seedling shoots of maize (Zea mays L.). The labeled substrates
      [13C,3H]GA12-aldehyde, [13C,3H]GA12, [14C4]GA53, [14C4/2H2]GA44, and
      [14C4/2H2]GA19 were fed individually to dwarf-5 vegetative shoots. Both
      [13C,3H]GA12-aldehyde and [13C,3H]GA12 were also added individually to normal
      shoots. The labeled metabolites were identified by full-scan gas chromatography
      mass spectrometry and Kovats retention indices. GA12-aldehyde was metabolized to
      GA53-aldehyde, GA12, GA53, GA44, and GA19; GA12 was metabolized to 2[beta]
      hydroxy-GA12, GA53, 2[beta]-hydroxyGA53, GA44, 2[beta]-hydroxyGA44, and GA19;
      GA53 was metabolized to GA44, GA19, GA20, and GA1; GA44 was metabolized to GA19;
      and GA19 was metabolized to GA20. These results, together with previously
      published data from this laboratory, document the most completely defined
      gibberellin pathway for the vegetative tissues of higher plants.

PMID- 12226194
TI  - Transfer RNA Is the Source of Extracellular Isopentenyladenine in a Ti
      Plasmidless Strain of Agrobacterium tumefaciens.
AB  - Even in the absence of the classical Ti plasmid-encoded cytokinin biosynthetic
      genes ipt and tzs, Agrobacterium tumefaciens strains still release significant
      amounts of the cytokinin isopentenyladenine (iP) into the culture medium (R.W.
      Kaiss-Chapman and R.O. Morris [1977] Biochem Biophys Res Commun 76: 453-459). A
      potential source of the iP is isopentenylated transfer RNA (tRNA), which, in
      turn, is synthesized by the activity of tRNA:isopentenyltransferase encoded by
      the bacterial miaA gene. To determine whether secreted iP had its origin in
      isopentenylated tRNA, a miaA- deletion/insertion mutant was prepared and
      reconstructed in Agrobacterium tumefaciens in vivo. The mutant no longer
      possessed tRNA:isopentenylation activity and no longer released iP into the
      extracellular medium. Transfer RNA therefore makes a small but significant
      contribution to the total amount of cytokinin normally secreted by Agrobacterium
      strains. tRNA-mediated synthesis may also account for cytokinin production by
      other plant-associated bacteria, such as Rhizobia, that have been reported to
      secrete similarly low levels of nonhydroxylated cytokinins.

PMID- 12226195
TI  - Phytochrome A Mediates the Promotion of Seed Germination by Very Low Fluences of
      Light and Canopy Shade Light in Arabidopsis.
AB  - Seeds of the wild type (WT) and of the phyA and phyB mutants of Arabidopsis
      thaliana were exposed to single red light (R)/far-red light (FR) pulses predicted
      to establish a series of calculated phytochrome photoequilibria (Pfr/P). WT and
      phyB seeds showed biphasic responses to Pfr/P. The first phase, i.e. the very-low
      fluence response (VLFR), occurred below Pfr/P = 10-1%. The second phase, i.e. the
      low-fluence response, occurred above Pfr/P = 3%. The VLFR was similarly induced
      by either a FR pulse saturating photoconversion or a subsaturating R pulse
      predicted to establish the same Pfr/P. The VLFR was absent in phyA seeds, which
      showed a strong low-fluence response. In the field, even brief exposures to the
      very low fluences of canopy shade light (R/FR ratio < 0.05) promoted germination
      above dark controls in WT and phyB seeds but not in the phyA mutant. Seeds of the
      phyA mutant germinated normally under canopies providing higher R/FR ratios or
      under deep canopy shade light supplemented with R from light-emitting diodes. We
      propose that phytochrome A mediates VLFR of A. thaliana seeds.

PMID- 12226196
TI  - Envelope Membranes from Spinach Chloroplasts Are a Site of Metabolism of Fatty
      Acid Hydroperoxides.
AB  - Enzymes in envelope membranes from spinach (Spinacia oleracea L.) chloroplasts
      were found to catalyze the rapid breakdown of fatty acid hydroperoxides. In
      contrast, no such activities were detected in the stroma or in thylakoids. In
      preparations of envelope membranes, 9S-hydroperoxy-10(E),12(Z)-octadecadienoic
      acid, 13S-hydroperoxy-9(Z),11(E)-octadecadienoic acid, or 13S-hydroperoxy
      9(Z),11(E),15(Z)-octadecatrienoic acid were transformed at almost the same rates
      (1-2 [mu]mol min-1 mg-1 protein). The products formed were separated by reversed
      phase high-pressure liquid chromatography and further characterized by gas
      chromatography-mass spectrometry. Fatty acid hydroperoxides were cleaved (a) into
      aldehydes and oxoacid fragments, corresponding to the functioning of a
      hydroperoxide lyase, (b) into ketols that were spontaneously formed from allene
      oxide synthesized by a hydroperoxide dehydratase, (c) into hydroxy compounds
      synthesized enzymatically by a system that has not yet been characterized, and
      (d) into oxoenes resulting from the hydroperoxidase activity of a lipoxygenase.
      Chloroplast envelope membranes therefore contain a whole set of enzymes that
      catalyze the synthesis of a variety of fatty acid derivatives, some of which may
      act as regulatory molecules. The results presented demonstrate a new role for the
      plastid envelope within the plant cell.

PMID- 12226197
TI  - Sucrose Represses the Developmentally Controlled Transient Activation of the
      Plastocyanin Gene in Arabidopsis thaliana Seedlings.
AB  - The plastocyanin (PC) gene of Arabidopsis thaliana is activated independently of
      light during early seedling development. In etiolated seedlings, PC mRNA levels
      increase transiently and a maximum dark level is reached after 2 d of growth in
      darkness. In etiolated transgenic seedlings carrying a chimeric PC-promoter:
      luciferase fusion gene, luciferase activity is similarly increased after 2 d of
      growth. The transient increase in PC mRNA and luciferase activity levels can be
      repressed by sucrose. Nonmetabolizable sugars and polyethylene glycol do not have
      a major effect on PC gene expression. Also, light-grown seedlings show a similar
      transient and sucrose-sensitive increase in PC mRNA levels and luciferase
      activity, as in dark-grown seedlings, but here expression levels are 15- fold
      higher. These findings suggest the presence of a sucrose-sensitive,
      developmentally controlled expression mechanism that operates independently of
      light.

PMID- 12226198
TI  - Diauxic Growth in Rice Suspension Cells Grown on Mixed Carbon Sources of Acetate
      and Glucose.
AB  - Diauxic growth was observed in rice (Oryza sativa L.) suspension cells growing on
      acetate (10 mM) and glucose (10 mM). Cells used acetate during the first growth
      phase and the acetate level in the medium was rapidly decreased, whereas the
      level of glucose remained essentially unchanged. After acetate was depleted from
      the medium, cells started to use glucose, forming the second growth phase. It
      appears that uptake of [14C]glucose was repressed during the first growth phase
      and became active during the second growth phase. In contrast, uptake of
      [14C]acetate occurred actively throughout the diauxic growth. By further
      demonstrating the specific induction of isocitrate lyase (EC 4.1.3.1), a
      glyoxylate cycle enzyme, and hexokinase (EC 2.7.1.1), a glycolysis enzyme, during
      the first and second growth phases, respectively, it was clearly shown that rice
      cells use acetate first and do not use both carbon sources simultaneously. This
      kind of diauxic growth pattern has been observed in bacteria. To our knowledege,
      this study is the first report demonstrating the presence of diauxic growth in
      plant cells.

PMID- 12226199
TI  - Kinetic Studies on the Xanthophyll Cycle in Barley Leaves (Influence of Antenna
      Size and Relations to Nonphotochemical Chlorophyll Fluorescence Quenching).
AB  - Xanthophyll-cycle kinetics as well as the relationship between the xanthophyll de
      epoxidation state and Stern-Volmer type nonphotochemical chlorophyll (Chl)
      fluorescence quenching (qN) were investigated in barley (Hordeum vulgare L.)
      leaves comprising a stepwise reduced antenna system. For this purpose plants of
      the wild type (WT) and the Chl b-less mutant chlorina 3613 were cultivated under
      either continuous (CL) or intermittent light (IML). Violaxanthin (V) availability
      varied from about 70% in the WT up to 97 to 98% in the mutant and IML-grown
      plants. In CL-grown mutant leaves, de-epoxidation rates were strongly accelerated
      compared to the WT. This is ascribed to a different accessibility of V to the de
      epoxidase due to the existence of two V pools: one bound to light-harvesting Chl
      a/b-binding complexes (LHC) and the other one not bound. Epoxidation rates (k)
      were decreased with reduction in LHC protein contents: kWT > kmutant >> kIML
      plants. This supports the idea that the epoxidase activity resides on certain LHC
      proteins. Irrespective of huge zeaxanthin and antheraxanthin accumulation, the
      capacity to develop qN was reduced stepwise with antenna size. The qN level
      obtained in dithiothreitol-treated CL- and IML-grown plants was almost identical
      with that in untreated IML-grown plants. The findings provide evidence that
      structural changes within the LHC proteins, mediated by xanthophyll-cycle
      operation, render the basis for the development of a major proportion of qN.

PMID- 12226200
TI  - The Auxin Transport Inhibitor N-(1-Naphthyl)phthalamic Acid Elicits Pseudonodules
      on Nonnodulating Mutants of White Sweetclover.
AB  - The collection of symbiotic (sym) mutants of white sweetclover (Melilotus alba
      Desr.) provides a developmental sequence of mutants blocked early in infection or
      nodule organogenesis. Mutant phenotypes include non-nodulating mutants that
      exhibit root-hair deformations in response to Rhizobium meliloti, mutants that
      form ineffective nodules lacking infection threads, and mutants that form
      infection threads and ineffective nodules. Mutant alleles from both the sym-1 and
      the sym-3 loci exhibited a non-nodulating phenotype in response to R. meliloti,
      although one allele in the sym-1 locus formed ineffective nodules at a low
      frequency. Spot-inoculation experiments on a non-nodulating allele in the sym-3
      locus indicated that this mutant lacked cortical cell divisions following
      inoculation with R. meliloti. The auxin transport inhibitor N-(1
      naphthyl)phthalamic acid elicited development of pseudonodules at a high
      frequency on all of the sweetclover sym mutants, including the non-nodulating
      mutants, in which the early nodulin ENOD2 was expressed. This suggests that N-(1
      naphthyl)phthalamic acid activates cortical cell divisions by circumventing a
      secondary signal transduction event that is lacking in the non-nodulating
      sweetclover mutants. The sym-3 locus and possibly the sym-1 locus appear to be
      essential to early host plant responses essential to nodule organogenesis.

PMID- 12226201
TI  - Isolation of Intact Protein Storage Vacuoles from Barley Aleurone (Identification
      of Aspartic and Cysteine Proteases).
AB  - Within the cereal aleurone reserve proteins are stored in specialized organelles,
      the protein storage vacuoles (PSV). We developed an aqueous method for the
      isolation of intact PSV. Barley (Hordeum vulgare L. cv Himalaya) aleurone
      protoplasts were gently lysed by passing them through a syringe needle. PSV were
      separated from cytoplasmic components by microfiltration and low-speed
      centrifugation. Isolated PSV appeared by light microscopy to be identical with
      those within barley aleurone protoplasts. Luminal contents were retained
      throughout the isolation procedure. We used isolated PSV to identify and
      characterize PSV-associated proteolytic activities. Isolated PSV contained
      cysteine proteases and aspartic proteases (APs). Gibberellic acid treatment of
      protoplasts increased cysteine protease activity. Protein blots probed with anti
      H. vulgare aspartic proteinase (HvAP) indicated that one PSV-AP was HvAP.
      Immunocytochemical localization by electron microscopy confirmed the presence of
      HvAP within the lumen of PSV. We conclude that isolated barley aleurone PSV will
      be useful in further characterizing this organelle.

PMID- 12226202
TI  - Whole-Nodule Carbon Metabolites Are Not Involved in the Regulation of the Oxygen
      Permeability and Nitrogenase Activity in White Clover Nodules.
AB  - To test the hypothesis of an indirect or direct involvement of carbon metabolites
      in the short-term regulation of nitrogenase activity, nodule O2 permeability was
      manipulated either by defoliation or by varying rhizosphere O2 partial pressure.
      In contrast to defoliation, a 50% reduction of the nodule O2 permeability, due to
      adapting nodules to 40 kPa O2, had no effect on nodule sucrose concentration.
      Likewise, total concentrations of other carbon metabolites such as fructose,
      starch, L-malate, and succinate tended to be differentially affected by the two
      treatments. Upon defoliation, carbon metabolites in roots responded in a manner
      similar to those in nodules. Sucrose concentration in nodules decreased
      significantly after the removal of 40% of the leaf area, which is known to have
      no effect on nitrogenase activity and O2 permeability. During regrowth after a
      100% defoliation, nitrogenase activity could be increased at any time by
      elevating rhizospheric O2 partial pressure. Thus, during the entire growing cycle
      nitrogenase activity seems primarily oxygen limited. Changes in whole nodule
      sucrose pools after defoliation have to be viewed as secondary effects not
      necessarily linked to nodule activity. Whole-nodule carbon metabolites appear not
      to be determinants of nodule activity, either through direct metabolic
      involvement or through indirect effects such as triggering O2 permeability.

PMID- 12226203
TI  - An Endo-[beta]-Mannanase Develops Exclusively in the Micropylar Endosperm of
      Tomato Seeds Prior to Radicle Emergence.
AB  - A galactomannan-hydrolyzing enzyme that develops pregerminatively in the
      micropylar region of the endosperm of the tomato (Lycopersicon esculentum [L.]
      Mill.) seed was characterized. The enzyme was endo-[beta]-mannanase (EC
      3.2.1.78), since it hydrolyzed galactomannan into oligosaccharides with no
      release of galactose and mannose. The mobility of this pregerminative enzyme in
      sodium dodecyl sulfate and native polyacrylamide gel electrophoresis was not
      identical to that of any of the three endo-[beta]-mannanases that develop in the
      same tissue (endosperm) after germination (H. Nonogaki, M. Nomaguchi, Y.
      Morohashi [1995] Physiol Plant 94: 328-334). There were also some differences in
      the products of galactomannan hydrolysis between the pregerminative and the
      postgerminative enzymes, indicating that the action pattern is different between
      the two types of enzymes. The pregerminative enzyme began to develop in the
      micropylar region of the endosperm at about 18 h postimbibition and increased up
      to the time immediately before radicle protrusion (24 h postimbibition). This
      enzyme was not present in the lateral part of the endosperm at any stage before
      or after germination. It is proposed that the enzyme develops prior to
      germination specifically at the micropylar region of the endosperm.

PMID- 12226204
TI  - Aluminum Interactions with Voltage-Dependent Calcium Transport in Plasma Membrane
      Vesicles Isolated from Roots of Aluminum-Sensitive and -Resistant Wheat
      Cultivars.
AB  - The role of Al interactions with root-cell plasma membrane (PM) Ca2+ channels in
      Al toxicity and resistance was studied. The experimental approach involved the
      imposition of a transmembrane electrical potential (via K+ diffusion) in right
      side-out PM vesicles derived from roots of two wheat (Triticum aestivum L.)
      cultivars (Al-sensitive Scout 66 and Al-resistant Atlas 66). We previously used
      this technique to characterize a voltage-dependent Ca2+ channel in the wheat root
      PM (J.W. Huang, D.L. Grunes, L.V. Kochian [1994] Proc Natl Acad Sci USA 91: 3473
      3477). We found that Al3+ effectively blocked this PM Ca2+ channel; however, Al3+
      blocked this Ca2+ channel equally well in both the Al-sensitive and -resistant
      cultivars. It was found that the differential genotypic sensitivity of this Ca2+
      transport system to Al in intact roots versus isolated PM vesicles was due to Al
      induced malate exudation localized to the root apex in Al-resistant Atlas but not
      in Al-sensitive Scout. Because malate can effectively chelate Al3+ in the
      rhizosphere and exclude it from the root apex, the differential sensitivity of
      Ca2+ influx to Al in intact roots of Al-resistant versus Al-sensitive wheat
      cultivars is probably due to the maintenance of lower Al3+ activities in the root
      apical rhizosphere of the resistant cultivar.

PMID- 12226205
TI  - Effect of Gibberellin and Heat Shock on the Lipid Composition of Endoplasmic
      Reticulum in Barley Aleurone Layers.
AB  - The heat-shock responses of barley (Hordeum vulgare L. cv Hi- malaya) aleurone
      layers incubated with or without gibberellic acid (GA3) were compared. Sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis revealed that heat shock
      blocked the synthesis and secretion of secretory proteins from GA3-treated layers
      but not untreated layers. This suppression of secretory protein synthesis has
      been correlated with changes in endoplasmic reticulum (ER) membranes (F.C.
      Belanger, M. R. Brodl, T.-h.D. Ho [1986] Proc Natl Acad Sci USA 83: 1354-1358; L.
      Sticher, A.K. Biswas, D.S. Bush, R.L. Jones [1990] Plant Physiol 92: 506-513).
      Our secretion data suggested that the ER membranes of aleurone layers incubated
      without GA3 may be more heat shock tolerant. To investigate this, the lipid
      profiles of membrane extracts in aleurone layers labeled with [14C]glycerol were
      examined. Heat shock markedly increased [14C]glycerol incorporation into
      phosphatidylcholine (PC), and gas chromatography revealed an increase in the
      amount of saturated fatty acids associated with thin layer chromatography
      purified PC in GA3-treated layers. In contrast, aleurone layers incubated without
      GA3 at normal temperature contained PC-associated fatty acids with a greater
      degree of saturation than GA3-treated layers. Heat shock modestly increased the
      degree of fatty acid saturation in untreated aleurone layers. This same trend was
      noted in fatty acids isolated from ER membranes purified by continuous sucrose
      density centrifugation. We propose that increased fatty acid saturation may help
      sustain ER membrane function in heat-shocked aleurone layers incubated in the
      absence of GA3.

PMID- 12226206
TI  - Overexpression of Copper/Zinc Superoxide Dismutase in the Cytosol of Transgenic
      Tobacco Confers Partial Resistance to Ozone-Induced Foliar Necrosis.
AB  - Ozone damage to plants has been attributed to the action of oxygen free-radicals
      and other ozone degradation products against which cellular antioxidant systems
      have been considered to be a front-line defense. The activity of superoxide
      dismutase (SOD), one such antioxidant, has been shown to increase in ozonated
      plants. Past work with pea (Pisum sativum L.) in our laboratory showed that the
      cytosolic Cu/Zn-SOD isoform and its transcript were most responsive to ozone,
      compared to chloroplastic Cu/Zn-SOD. In the current work we tested the hypothesis
      that plants that constitutively overexpress cytosolic SOD are more tolerant of
      ozone. Pea cytosolic Cu/Zn-SOD was overproduced in the cytosol of two cultivars
      of transformed tobacco (Nicotiana tabacum), Bel W3 and Wisconsin 38. Young and
      recently expanded leaves of transgenic plants of both cultivars showed less
      foliar necrosis than nontransformed controls when exposed to acute doses of
      ozone. We suggest that this may demonstrate the importance of Cu/Zn-SOD in the
      cytosol as a protector of the integrity of the plasma membrane and possibly other
      cellular constituents.

PMID- 12226207
TI  - Allelic Analysis of the Maize amylose-extender Locus Suggests That Independent
      Genes Encode Starch-Branching Enzymes IIa and IIb.
AB  - Starch branching enzymes (SBE) catalyze the formation of [alpha]-1,6-glucan
      linkages in the biosynthesis of starch. Three distinct SBE isoforms have been
      identified in maize (Zea mays L.) endosperm, SBEI, IIa, and IIb. Independent
      genes have been identified that encode maize SBEI and IIb; however, it has
      remained controversial as to whether SBEIIa and IIb result from
      posttranscriptional processes acting on the product of a single gene or whether
      they are encoded by separate genes. To investigate this question, we analyzed 16
      isogenic lines carrying independent alleles of the maize amylose-extender (ae)
      locus, the structural gene for SBEIIb. We show that 22 d after pollination ae-B1
      endosperm expressed little Sbe2b (ae)-hybridizing transcript, and as expected, ae
      B1 endosperm also lacked detectable SBEIIb enzymatic activity. Significantly, we
      show that ae-B1 endosperm contained SBEIIa enzymatic activity, strongly
      supporting the hypothesis that endosperm SBEIIa and IIb are encoded by separate
      genes. Furthermore, we show that in addition to encoding the predominant Sbe2b
      hybridizing message expressed in endosperm, the ae gene also encodes the major
      Sbe2b-like transcript expressed in developing embryos and tassels.

PMID- 12226208
TI  - The Superoxide Synthases of Plasma Membrane Preparations from Cultured Rose
      Cells.
AB  - Preparations of plasma membranes isolated from cultured rose (Rosa damascena
      Mill. cv Gloire de Guilan) cells synthesized O2- when incubated with either NADH
      or NADPH, as measured by an O2--specific assay based on the chemiluminescence of
      lucigenin. The activities were strongly dependent on the presence of Triton X
      100. The Km for NADH was 159 [mu]M; that for NADPH was 19 [mu]M. Neither NADH-
      nor NADPH-dependent activity was inhibited by azide, an inhibitor of peroxidase,
      nor by antimycin A, an inhibitor of mitochondrial electron transport; both
      activities were inhibited by 30 to 100 nM diphenylene iodonium, an inhibitor of
      the mammalian NADPH oxidase. The NADH- and NADPH-dependent activities could be
      distinguished by detergent solubilization and ultracentrifugation: the NADH
      dependent activity sedimented more easily, whereas the NADPH-dependent activity
      remained in suspension. One or both of these enzymes may provide the O2- seen
      when plant cells are exposed to pathogens or pathogen-associated elicitors;
      however, plasma membranes from rose cells treated with a Phytophthora elicitor
      had the same activity as control cells.

PMID- 12226209
TI  - Cell-Free Transfer of Phosphatidylinositol between Membrane Fractions Isolated
      from Soybean.
AB  - Transfer of phosphatidylinositol (PI) between membranes was reconstituted in a
      cell-free system using membrane fractions isolated from dark-grown soybean
      (Glycine max [L.] Merr.). Donor membrane vesicles contained [3H]myo-inositol
      labeled PI. A fraction enriched in endoplasmic reticulum was a more efficient
      donor than its parent microsomal membrane fraction. As acceptor, cytoplasmic side
      out plasma membrane vesicles were more efficient than cytoplasmic side-in plasma
      membrane vesicles. Endoplasmic reticulum was also an efficient acceptor,
      suggesting that transfer occurred to cytoplasmic membrane leaflets. PI transfer
      was time and temperature dependent but did not require cytosolic proteins, ATP,
      GTP, cytosol, and acyl-coenzyme A. These results suggest that neither lipid
      transfer proteins nor transition vesicles, similar to those involved in vesicle
      trafficking from endoplasmic reticulum to the Golgi apparatus, were involved. In
      the presence of Mg2+ and ATP, endoplasmic reticulum PI was not metabolized,
      whereas PI transferred to the plasma membrane was metabolized into
      phosphatidylinositol monophosphate and phosphatidylinositol bisphosphate. To
      summarize, the cell-free transfer of endoplasmic reticulum-derived PI was
      distinct from, for example, vesicle transport from endoplasmic reticulum to Golgi
      apparatus, not only in its regulation but also in its acceptor unspecificity.

PMID- 12226210
TI  - Defense-Related Transcript Accumulation in Phaseolus vulgaris L. Colonized by the
      Arbuscular Mycorrhizal Fungus Glomus intraradices Schenck Smith.
AB  - Accumulation of mRNAs for the defense-related genes phenylalanine ammonia-lyase
      (PAL), chalcone synthase, chitinase (CHT), glucanase, and hydroxyproline-rich
      glycoprotein were examined in roots of dark red kidney bean (Phaseolus vulgaris
      L. cv Moncalm) colonized by the arbuscular mycorrhizal fungus Glomus intraradices
      Schenck & Smith. In three separate experiments the root length colonized ranged
      from 28 to 55% by 28 d after planting and inoculation. RNA blot analysis revealed
      little change in the accumulations of PAL, chalcone synthase, CHT, glucanase, and
      hydroxyproline-rich glycoprotein transcripts from the 28-d mycorrhizal roots
      compared to the uninoculated controls. Normalizing the ratios of defense-related
      transcript accumulation against RNA pools regarded as being constitutively
      expressed, actin mRNA, 25S rRNA, and 18S rRNA, indicated that changes in the
      ratios of up to 20% occur according to the RNA pool used for normalization. In
      situ hybridizations of colonized roots using probes for PAL and CHT showed that
      accumulations of both transcripts occurred only in arbusculated cells. Both
      young, finely branched arbuscules and older, clumped arbuscules displayed PAL and
      CHT message accumulations. The PAL and CHT mRNA accumulations were greater in
      cortical cells containing young arbuscules than in cells containing clumped
      arbuscules. Intercellular hyphae and vesicles elicited no response.

PMID- 12226211
TI  - Differential Effects of Nitrogen Limitation on Photosynthetic Efficiency of
      Photosystems I and II in Microalgae.
AB  - The effects of nitrogen starvation on photosynthetic efficiency were examined in
      three unicellular algae by measuring changes in the quantum yield of fluorescence
      with a pump-and-probe method and thermal efficiency (i.e. the percentage of
      trapped energy stored photochemically) with a pulsed photoacoustic method
      together with the inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea to
      distinguish photosystems I and II (PSI and PSII). Measured at 620 nm, maximum
      thermal efficiency for both photosystems was 32% for the diatom Thalassiosira
      weissflogii (PSII:PSI ratio of 2:1), 39% for the green alga Dunaliella
      tertiolecta (PSII:PSI ratio of 1:1), and 29% for the cyanobacterium Synechococcus
      sp. PCC 7002 (PSII:PSI ratio of 1:2). Nitrogen starvation decreased total thermal
      efficiency by 56% for T. weissflogii and by 26% for D. tertiolecta but caused no
      change in Synechococcus. Decreases in the number of active PSII reaction centers
      (inferred from changes in variable fluorescence) were larger: 86% (T.
      weissflogii), 65% (D. tertiolecta), and 65% (Synechococcus). The selective
      inactivation of PSII under nitrogen starvation was confirmed by independent
      measurements of active PSII using oxygen flash yields and active PSI using P700
      reduction. Relatively high thermal efficiencies were measured in all three
      species in the presence of the PSII inhibitor 3-(3,4-dichlorophenyl)-1,1
      dimethylurea, suggesting the potential for significant cyclic electron flow
      around PSI. Fluorescence or photoacoustic data agreed well; in T. weissflogii,
      the functional cross-sectional area of PSII at 620 nm was estimated to be the
      same using both methods (approximately 1.8 x 102 A2). The effects of nitrogen
      starvation occur mainly in PSII and are well represented by variable fluorescence
      measurements.

PMID- 12226212
TI  - Na+-K+ Exchange at the Xylem/Symplast Boundary (Its Significance in the Salt
      Sensitivity of Soybean).
AB  - We investigated the mechanism of Na+ reabsorption in exchange for K+ at the
      xylem/symplast boundary of soybean roots (Glycine max var Hodgson). The xylem
      vessels of excised roots were perfused with solutions of defined composition to
      discriminate between entry of ions into or reabsorption from the xylem vessels.
      In the presence of NaCl, the transport systems released K+ into the xylem sap and
      reabsorbed Na+. The Na+-K+ exchange was energized by proton-translocating
      ATPases, enhanced by external K+ concentration, and dependent on the anion
      permeability. Evidence was presented for the operation of H+/Na+ and H+/K+
      antiporters at the xylem/symplast interface.

PMID- 12226213
TI  - Promises and Prospects of Phytoremediation.

PMID- 12226214
TI  - Cell-Wall Polysaccharides of Developing Flax Plants.
AB  - Flax (Linum usitatissimum L.) fibers originate from procambial cells of the
      protophloem and develop in cortical bundles that encircle the vascular cylinder.
      We determined the polysaccharide composition of the cell walls from various
      organs of the developing flax plant, from fiber-rich strips peeled from the stem,
      and from the xylem. Ammonium oxalate-soluble polysaccharides from all tissues
      contained 5-linked arabinans with low degrees of branching, rhamnogalacturonans,
      and polygalacturonic acid. The fiber-rich peels contained, in addition,
      substantial amounts of a buffer-soluble, 4-linked galactan branched at the 0-2
      and 0-3 positions with nonreducing terminal-galactosyl units. The cross-linking
      glycans from all tissues were (fucogalacto)xyloglucan, typical of type-I cell
      walls, xylans containing (1->)-[beta]-D-xylosyl units branched exclusively at the
      xylosyl O-2 with t-(4-O-methyl)-glucosyluronic acid units, and
      (galacto)glucomannans. Tissues containing predominantly primary cell wall
      contained a larger proportion of xyloglucan. The xylem cells were composed of
      about 60% 4-xylans, 32% cellulose, and small amounts of pectin and the other
      cross-linking polysaccharides. The noncellulosic polysaccharides of flax exhibit
      an uncommonly low degree of branching compared to similar polysaccharides from
      other flowering plants. Although the relative abundance of the various
      noncellulosic polysaccharides varies widely among the different cell types, the
      linkage structure and degree of branching of several of the noncellulosic
      polysaccharides are invariant.

PMID- 12226215
TI  - The Active Oxygen Response of Cell Suspensions to Incompatible Bacteria Is Not
      Sufficient to Cause Hypersensitive Cell Death.
AB  - The inoculation of tobacco (Nicotiana tabacum L.) suspension cells with bacterial
      pathogens that elicit the hypersensitive response (HR) in leaves has been shown
      to elicit production of active oxygen. This response occurs in two phases, the
      second of which occurs 1 to 3 h after bacterial addition and is unique to HR
      causing interactions. The relationship between the phase II active oxygen
      response and the HR was characterized using Pseudomonas syringae pv syringae and
      P. fluorescens (pHIR11), which contains a cosmid clone of the hrp/hrm region from
      P. syringae pv syringae. TnphoA mutations in complementation groups II through
      XIII of the hrp cluster blocked the phase II active oxygen response, whereas
      mutations in the group I hrmA locus did not affect phase II. Despite the normal
      active oxygen response, bacteria with mutations in the hrmA region did not cause
      the HR in intact tobacco leaves nor did they induce hypersensitive cell death in
      cell suspensions. The data indicate that the bacteria do not require the hrmA
      region to elicit active oxygen production, but a full and intact hrp/hrm region
      is required to elicit hypersensitive cell death. Therefore, the phase II active
      oxygen response does not directly cause hypersensitive cell death nor is the
      response itself sufficient to trigger the HR.

PMID- 12226216
TI  - Purification and Characterization of the Bifunctional Enzyme Lysine-Ketoglutarate
      Reductase-Saccharopine Dehydrogenase from Maize.
AB  - The first enzyme of the lysine degradation pathway in maize (Zea mays L.), lysine
      ketoglutarate reductase, condenses lysine and [alpha]-ketoglutarate into
      saccharopine using NADPH as a cofactor, whereas the second, saccharopine
      dehydrogenase, converts saccharopine to [alpha]-aminoadipic-[delta]-semialdehyde
      and glutamic acid using NAD+ or NADP+ as a cofactor. The reductase and
      dehydrogenase activities are optimal at pH 7.0 and 9.0, respectively. Both enzyme
      activities, co-purified on diethylaminoethyl-cellulose and gel filtration
      columns, were detected on nondenaturing polyacrylamide gels as single bands with
      identical electrophoretic mobilities and share tissue specificity for the
      endosperm. The highly purified preparation containing the reductase and
      dehydrogenase activities showed a single polypeptide band of 125 kD on sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. The native form of the enzyme
      is a dimer of 260 kD. Limited proteolysis with elastase indicated that lysine
      ketoglutarate reductase and saccharopine dehydrogenase from maize endosperm are
      located in two functionally independent domains of a bifunctional polypeptide.

PMID- 12226217
TI  - Kinetics of NH4+ Influx in Spruce.
AB  - Influxes of 13NH4+ across the root plasmalemma were measured in intact seedlings
      of Picea glauca (Moench) Voss. Two kinetically distinct uptake systems for NH4+
      were identified. In N-deprived plants, a Michaelis-Menten-type high-affinity
      transport system (HATS) operated in a 2.5 to 350 [mu]M range of external NH4+
      concentration ([NH4 +]o). The Vmax of this HATS was 1.9 to 2.4 [mu]mol g-1 h-1,
      and the Km was 20 to40 [mu]M. At [NH4+]o from 500 [mu]M to 50 mM, a linear low
      affinity system (LATS) was apparent. Both HATS and LATS were constitutive. A time
      dependence study of NH4+ influx in previously N-deprived seedlings revealed a
      small transient increase of NH4+ influx after 24 h of exposure to 100 [mu]M
      [NH4+]o. This was followed by a decline of influx to a steady-state value after 4
      d. In seedlings exposed to 100 [mu]M external NO3- concentration for 3 d, the
      Vmax for NH4+ uptake by HATS was increased approximately 30% compared to that
      found in N-deprived seedlings, whereas LATS was down-regulated. The present study
      defines the much higher uptake capacity for NH4+ than for N03- in seedlings of
      this species.

PMID- 12226218
TI  - Purification and Properties of Flavin- and Molybdenum-Containing Aldehyde Oxidase
      from Coleoptiles of Maize.
AB  - Aldehyde oxidase (AO; EC 1.2.3.1) that could oxidize indole-3-acetaldehyde into
      indole-3-acetic acid was purified approximately 2000-fold from coleoptiles of 3-d
      old maize (Zea mays L.) seedlings. The apparent molecular mass of the native
      enzyme was about 300 kD as estimated by gel-filtration column chromatography.
      Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the
      enzyme was composed of 150-kD subunits. It contained flavin adenine dinucleotide,
      iron, and molybdenum as prosthetic groups and had absorption peaks in the visible
      region (300-600 nm). To our knowledge, this is the first demonstration of the
      presence of flavin adenine dinucleotide and metals in plant AO. Other aromatic
      aldehydes such as indole-3-aldehyde and benzaldehyde also served as good
      substrates, but N-methylnicotinamide, a good substrate for animal AO, was not
      oxidized. 2-Mercaptoethanol, p-chloromercu-ribenzoate, and iodoacetate partially
      inhibited the activity, but well-known inhibitors of animal AO, such as menadione
      and estradiol, caused no reduction in activity. These results indicate that,
      although maize AO is similar to animal enzymes in molecular mass and cofactor
      components, it differs in substrate specificity and susceptibility to inhibitors.
      Immunoblotting analysis with mouse polyclonal antibodies raised against the
      purified maize AO showed that the enzyme was relatively rich in the apical region
      of maize coleoptiles. The possible role of this enzyme is discussed in relation
      to phytohormone biosynthesis in plants.

PMID- 12226219
TI  - Aromatic Polyketide Synthases (Purification, Characterization, and Antibody
      Development to Benzalacetone Synthase from Raspberry Fruits).
AB  - p-Hydroxyphenylbutan-2-one, the characteristic aroma compound of raspberries
      (Rubus idaeus L.), is synthesized from p-coumaryl-coenzyme A and malonyl-coenzyme
      A in a two-step reaction sequence that is catalyzed by benzalacetone synthase and
      benzalacetone reductase (W. Borejsza-Wysocki and G. Hrazdina [1994]
      Phytochemistry 35: 623-628). Benzalacetone synthase condenses one malonate with p
      coumarate to form the pathway intermediate p-hydroxyphenylbut-3-ene-2-one (p
      hydroxybenzalacetone) in a reaction that is similar to those catalyzed by
      chalcone and stilbene synthases. We have obtained an enzyme preparation from ripe
      raspberries that was preferentially enriched in benzalacetone synthase
      (approximately 170-fold) over chalcone synthase (approximately 14-fold) activity.
      This preparation was used to characterize benzalacetone synthase and to develop
      polyclonal antibodies in rabbits. Benzalacetone synthase showed similarity in its
      molecular properties to chalcone synthase but differed distinctly in its
      substrate specificity, response to 2-mercaptoethanol and ethylene glycol, and
      induction in cell-suspension cultures. The product of the enzyme, p
      hydroxybenzalacetone, inhibited mycelial growth of the raspberry pathogen
      Phytophthora fragariae var rubi at 250 [mu]M. We do not know whether the dual
      activity in the benzalacetone synthase preparation is the result of a
      bifunctional enzyme or is caused by contamination with chalcone synthase that was
      also present. The rapid induction of the enzyme in cell-suspension cultures upon
      addition of yeast extract and the toxicity of its product, p
      hydroxybenzalacetone, to phytopathogenic fungi also suggest that the pathway may
      be part of a plant defense response.

PMID- 12226220
TI  - Peroxygenase-Catalyzed Fatty Acid Epoxidation in Cereal Seeds (Sequential
      Oxidation of Linoleic Acid into 9(S),12(S),13(S)-Trihydroxy-10(E)-Octadecenoic
      Acid).
AB  - Peroxygenase-catalyzed epoxidation of oleic acid in preparations of cereal seeds
      was investigated. The 105,000g particle fraction of oat (Avena sativa) seed
      homogenate showed high peroxygenase activity, i.e. 3034 [plus or minus] 288 and
      2441 [plus or minus] 168 nmol (10 min)-1 mg-1 protein in two cultivars, whereas
      the corresponding fraction obtained from barley (Hordeum vulgare and Hordeum
      distichum), rye (Secale cereale), and wheat (Triticum aestivum) showed only weak
      activity, i.e. 13 to 138 nmol (10 min)-1 mg-1 protein. In subcellular fractions
      of oat seed homogenate, peroxygenase specific activity was highest in the
      105,000g particle fraction, whereas lipoxygenase activity was more evenly
      distributed and highest in the 105,000g supernatant fraction. Incubation of [1
      14C]linoleic acid with the 105,000g supernatant of oat seed homogenate led to the
      formation of several metabolites, i.e. in order of decreasing abundance, 9(S)
      hydroxy-10(E),12(Z)-octadecadienoic acid, 9(S),12(S),13(S)-trihydroxy-10(E)
      octadecenoic acid, cis-9,10-epoxy-12(Z)-octadecenoic acid [mainly the 9(R),10(S)
      enantiomer], cis-12,13-epoxy-9(Z)-octadecenoic acid [mainly the 12(R),13(S)
      enantiomer], threo-12,13-dihydroxy-9(Z)-octadecenoic acid, and 12(R),13(S)-epoxy
      9(S)-hydroxy-10(E)-octadecenoic acid. Incubation of linoleic acid with the
      105,000g particle fraction gave a similar, but not identical, pattern of
      metabolites. Conversion of linoleic acid into 9(S),12(S),13(S)-trihydroxy-10(E)
      octadecenoic acid, a naturally occurring oxylipin with antifungal properties,
      took place by a pathway involving sequential catalysis by lipoxygenase,
      peroxygenase, and epoxide hydrolase.

PMID- 12226221
TI  - Polyamine Binding to Plasma Membrane Vesicles Isolated from Zucchini Hypocotyls.
AB  - The general features of [14C]spermidine binding to plasmalemma vesicles isolated
      from zucchini (Cucurbita pepo L.) etiolated hypocotyls are reported in the
      present paper. The specific interaction of the polyamine with the plasma
      membranes was reversible and thermolabile, since it decreased by about 50% in the
      assay performed at 40[deg]C compared to that carried out on ice. On the contrary,
      nonspecific binding was unaffected by temperature. Specific spermidine binding
      showed a pH dependence with a maximum at pH 8.0 and it reached saturation between
      0.75 and 1 mM external spermidine concentration. The value of the dissociation
      constant calculated from Scatchard analysis was 4.4 x 10-5 M. Specific spermidine
      interaction appeared to be sensitive to detergents and was markedly reduced by
      the presence of divalent cations, such as Mg2+ and Ca2+, whereas it was
      stimulated by monovalent cations. Polyamine binding sites were highly sensitive
      to pronase treatment. Competition experiments, performed using a series of
      compounds structurally related to spermidine, may provide some indication of the
      characteristics of spermidine binding sites. The results presented here suggest
      that specific spermidine binding occurs mainly with the protein component of the
      plasma membrane.

PMID- 12226222
TI  - Nucleotides and Nucleotide Sugars in Developing Maize Endosperms (Synthesis of
      ADP-Glucose in brittle-1).
AB  - As part of an in vivo study of carbohydrate metabolism during development of Zea
      mays L. kernels, quantities of nucleotides and nucleotide sugars were measured in
      endosperm extracts from normal, the single-mutant genotypes shrunken-1 (sh1),
      shrunken-2 (sh2), and brittle-1 (btl}, and the multiple-mutant genotypes sh1bt1,
      sh2bt1, and sh1sh2bt1. Results showed that bt1 kernels accumulated more than 13
      times as much adenosine 5[prime] diphospho-glucose (ADP-Glc) as normal kernels.
      Activity of starch synthase in bt1 endosperm was equal to that in endosperm
      extracts from normal kernels. Thus the ADP-Glc accumulation in bt1 endosperm
      cells was not due to a deficiency in starch synthase. ADP-Glc content in extracts
      of sh1bt1 endosperms was similar to that in bt1, but in extracts of the sh2bt1
      mutant kernels ADP-Glc content was much reduced compared to bt1 (about 3 times
      higher than that in normal). Endosperm extracts from sh1sh2bt1, kernels that are
      deficient in both ADP-Glc pyrophosphorylase (AGPase) and sucrose synthase, had
      quantities of ADP-Glc much lower than in normal kernels. These results clearly
      indicate that AGPase is the predominant enzyme responsible for the in vivo
      synthesis of ADP-Glc in bt1 mutant kernels, but Suc synthase may also contribute
      to the synthesis of ADP-Glc in kernels deficient in AGPase.

PMID- 12226223
TI  - Immunolocalization of Antifreeze Proteins in Winter Rye Leaves, Crowns, and Roots
      by Tissue Printing.
AB  - During cold acclimation, antifreeze proteins (AFPs) that are similar to
      pathogenesis-related proteins accumulate in the apoplast of winter rye (Secale
      cereale L. cv Musketeer) leaves. AFPs have the ability to modify the growth of
      ice. To elucidate the role of AFPs in the freezing process, they were assayed and
      immunolocalized in winter rye leaves, crowns, and roots. Each of the total
      soluble protein extracts from cold-acclimated rye leaves, crowns, and roots
      exhibited antifreeze activity, whereas no antifreeze activity was observed in
      extracts from nonacclimated rye plants. Antibodies raised against three
      apoplastic rye AFPs, corresponding to a glucanase-like protein (GLP, 32 kD), a
      chitinase-like protein (CLP, 35 kD), and a thaumatin-like protein (TLP, 25 kD),
      were used in tissue printing to show that the AFPs are localized in the epidermis
      and in cells surrounding intercellular spaces in cold-acclimated plants. Although
      GLPs, CLPs, and TLPs were present in nonacclimated plants, they were found in
      different locations and did not exhibit antifreeze activity, which suggests that
      different isoforms of pathogenesis-related proteins are produced at low
      temperature. The location of rye AFPs may prevent secondary nucleation of cells
      by epiphytic ice or by ice propagating through the xylem. The distributions of
      pathogenesis-induced and cold-accumulated GLPs, CLPs, and TLPs are similar and
      may reflect the common pathways by which both pathogens and ice enter and
      propagate through plant tissues.

PMID- 12226224
TI  - Branching in Pea (Action of Genes Rms3 and Rms4).
AB  - The nonallelic ramosus mutations rms3-2 and rms4 of pea (Pisum sativum L.) cause
      extensive release of vegetative axillary buds and lateral growth in comparison
      with wild-type (cv Torsdag) plants, in which axillary buds are not normally
      released under the conditions utilized. Grafting studies showed that the
      expression of the rms4 mutation in the shoot is independent of the genotype of
      the root-stock. In contrast, the length of the branches at certain nodes of rms3
      2 plants was reduced by grafting to wild-type stocks, indicating that the wild
      type Rms3 gene may control the level of a mobile substance produced in the root.
      This substance also appears to be produced in the shoot because Rms3 shoots did
      not branch when grafted to mutant rms3-2 rootstocks. However, the end product of
      the Rms3 gene appears to differ from that of the Rms2 gene (C.A. Beveridge, J.J.
      Ross, and I.C. Murfet [1994] Plant Physiol 104: 953-959) because reciprocal
      grafts between rms3-2 and rms2 seedlings produced mature shoots with apical
      dominance similar to that of rms3-2 and rms2 shoots grafted to wild-type stocks.
      Indole-3-acetic acid levels were not reduced in apical or nodal portions of rms4
      plants and were actually elevated (up to 2-fold) in rms3-2 plants. It is
      suggested that further studies with these branching mutants may enable
      significant progress in understanding the normal control of apical dominance and
      the related communication between the root and shoot.

PMID- 12226225
TI  - Identification and Preliminary Characterization of a Ca2+- Dependent High
      Affinity Binding Site for Inositol-1,4,5-Trisphosphate from Chenopodium rubrum.
AB  - Using a radioligand-binding assay we have identified a Ca2+- dependent high
      affinity D-myo-inositol-1,4,5-trisphosphate (InsP3) binding site in a membrane
      vesicle preparation from Chenopodium rubrum. Millimolar concentrations of Ca2+
      were required to observe specific binding of [3H]InsP3. A stable equilibrium
      between bound and free ligand was established within 5 min and bound [3H]InsP3
      could be completely displaced by InsP3 in a time- and concentration-dependent
      manner. Displacement assays indicated a single class of binding sites with an
      estimated dissociation constant of 142 [plus or minus] 17 nM. Other inositol
      phosphates bound to the receptor with much lower affinity. The glycosaminoglycan
      heparin was an effective competitor for the binding site (inhibitor concentration
      for 50% displacement = 534 nM). ATP at higher, although physiologically relevant,
      concentrations (inhibitor concentration for 50% displacement = 241 [mu]M) also
      displaced [3H]InsP3 from the receptor. Recent studies in animals have highlighted
      the importance of Ca2+ regulation of InsP3-induced Ca2+ release. The potential
      for the operation of similar regulatory mechanisms in plants is discussed.

PMID- 12226226
TI  - Isolation and Identification of Ripening-Related Tomato Fruit Carboxypeptidase.
AB  - Tomato (Lycopersicon esculentum) fruit carboxypeptidase active on N-carbobenzoxy
      Z-L-phenylalanine-L-alanine was found to constitute a family of isoforms whose
      abundance changed differentially during ripening. A specific polyclonal antibody
      against the fruit carboxypeptidase was raised in rabbits and used to purify and
      identify the protein. The data from immunoaffinity chromatography,
      immunoinhibition studies, immunoprecipitation of the in vivo- and in vitro
      labeled proteins, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      analysis of native isoforms strongly suggest that the fruit carboxypeptidases are
      monomers or oligomers of 68- and/or 43-kD subunits.

PMID- 12226227
TI  - Tomato Fruit Carboxypeptidase (Properties, Induction upon Wounding, and
      Immunocytochemical Localization).
AB  - Carboxypeptidase activity was characterized during ripening and wounding of
      tomato (Lycopersicon esculentum) fruit. The fruit enzyme shares substrate
      specificity and susceptibility to the inhibitors diisopropyl fluorophosphate and
      phenylmethylsulfonyl fluoride with other plant carboxypeptidases. The abundance
      and stability of wound-induced carboxypeptidase were developmentally regulated.
      Oxidative stress caused by cupric ions impaired the membrane permeability in the
      slices from pink fruit, resulting in leakage of the carboxypeptidase into the
      medium and in its redistribution in the cell. The patterns of carboxypeptidase
      activity did not parallel the cupric ion effect on ethylene levels. Immunogold
      electron microscopy studies indicated that the fruit carboxypeptidase is
      associated with electron-dense inclusions in the vacuole.

PMID- 12226228
TI  - Doubling the CO2 Concentration Enhanced the Activity of Carbohydrate-Metabolism
      Enzymes, Source Carbohydrate Production, Photoassimilate Transport, and Sink
      Strength for Opuntia ficus-indica.
AB  - After exposure to a doubled CO2 concentration of 750 [mu]mol mol-1 air for about
      3 months glucose and starch in the chlorenchyma of basal cladodes of Opuntia
      ficus-indica increased 175 and 57%, respectively, compared with the current CO2
      concentration of 370 [mu]mol mol-1, but sucrose content was virtually unaffected.
      Doubling the CO2 concentration increased the nocturnal malate production in basal
      cladodes by 75%, inorganic phosphate (Pi) by 32%, soluble starch synthase
      activity by 30%, and sucrose-Pi synthase activity by 146%, but did not affect the
      activity of hexokinase. Doubling CO2 accelerated phloem transport of sucrose out
      of the basal cladodes, resulting in a 73% higher dry weight for the daughter
      cladodes. Doubling CO2 increased the glucose content in 14-d-old daughter
      cladodes by 167%, increased nocturnal malate production by 22%, decreased total
      amino acid content by 61%, and increased soluble starch synthase activity by 30%
      and sucrose synthase activity by 62%. No downward acclimation of photosynthesis
      during long-term exposure to elevated CO2 concentrations occurs for O. ficus
      indica (M. Cui, P.M. Miller, P.S. Nobel [1993] Plant Physiol 103: 519-524; P.S.
      Nobel, A.A. Israel [1994] J Exp Bot 45: 295-303), consistent with its higher
      source capacity and sink strength than under current CO2. These changes
      apparently do not result in Pi limitation of photosynthesis or suppression of
      genes governing photosynthesis for this perennial Crassulacean acid metabolism
      species, as occur for some annual crops.

PMID- 12226229
TI  - Determining Photosynthetic Parameters from Leaf CO2 Exchange and Chlorophyll
      Fluorescence (Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase Specificity Factor,
      Dark Respiration in the Light, Excitation Distribution between Photosystems,
      Alternative Electron Transport Rate, and Mesophyll Diffusion Resistance.
AB  - Using simultaneous measurements of leaf gas exchange and chlorophyll
      fluorescence, we determined the excitation partitioning to photosystem II (PSII),
      the CO2/O2 specificity of ribulose-1,5-bisphosphate carboxylase/oxygenase, the
      dark respiration in the light, and the alternative electron transport rate to
      acceptors other than bisphosphoglycerate, and the transport resistance for CO2 in
      the mesophyll cells for individual leaves of herbaceous and tree species. The
      specificity of ribulose-1,5-bisphosphate carboxylase/oxygenase for CO2 was
      determined from the slope of the O2 dependence of the CO2 compensation point
      between 1.5 and 21% O2. Its value, on the basis of dissolved CO2 and O2
      concentrations at 25.5[deg]C, varied between 86 and 89. Dark respiration in the
      light, estimated from the difference between the CO2 compensation point and the
      CO2 photocompensation point, was about 20 to 50% of the respiration rate in the
      dark. The excitation distribution to PSII was estimated from the extrapolation of
      the dependence of the PSII quantum yield on F/Fm to F = 0, where F is steady
      state and Fm is pulse-satuarated fluorescence, and varied between 0.45 and 0.6.
      The alternative electron transport rate was found as the difference between the
      electron transport rates calculated from fluorescence and from gas exchange, and
      at low CO2 concentrations and 10 to 21% O2, it was 25 to 30% of the maximum
      electron transport. The calculated mesophyll diffusion resistance accounted for
      about 20 to 30% of the total mesophyll resistance, which also includes
      carboxylation resistance. Whole-leaf photosynthesis is limited by gas phase,
      mesophyll diffusion, and carboxylation resistances in nearly the same proportion
      in both herbaceous species and trees.

PMID- 12226230
TI  - Modulation of an Intracellular Calmodulin-Stimulated Ca2+-Pumping ATPase in
      Cauliflower by Trypsin (The Use of Calcium Green-5N to Measure Ca2+ Transport in
      Membrane Vesicles).
AB  - The effect of controlled trypsin digestion of a calmodulin-stimulated Ca2+-ATPase
      in low-density intracellular membranes from cauliflower (Brassica oleracea L.)
      inflorescences was investigated. Ca2+ uptake into vesicles was measured either
      continuously with the fluorescent Ca2+ indicator Calcium Green-5N or with a radio
      active filter technique. Trypsin treatment of vesicles resulted in a 3-fold
      activation of Ca2+ uptake and loss of calmodulin sensitivity. Immunoblotting
      experiments with an antiserum raised against the Ca2+-ATPase showed that the
      trypsin activation was accompanied by a decrease in the amount of intact Ca2+
      ATPase (111 kD) and by successive appearances of polypeptides of 102 and 99 to 84
      kD. 125I-Calmodulin overlays showed that only the intact Ca2+-ATPase bound
      calmodulin. Removal of the calmodulin-binding domain (about 9 kD) was not enough
      to obtain full activation. Trypsin proteolysis resulted in a Ca2+ concentration
      necessary for half-maximal activity of 0.5 [mu]M, whereas a value of about 2
      [mu]M was obtained with untreated membranes in the presence of calmodulin.
      Without trypsin treatment or calmodulin the activity was not saturated even at 57
      [mu]M free Ca2+. The data suggest that trypsin digestion and calmodulin activate
      the cauliflower Ca2+-ATPase by at least partly different mechanisms.

PMID- 12226231
TI  - Cholinephosphotransferase and Diacylglycerol Acyltransferase (Substrate
      Specificities at a Key Branch Point in Seed Lipid Metabolism).
AB  - Many oilseed plants accumulate triacylglycerols that contain unusual fatty acyl
      structures rather than the common 16- and 18-carbon fatty acids found in membrane
      lipids of these plants. In vitro experiments demonstrate that triacylglycerols
      are synthesized via diacylglycerols in microsomal preparations and that this same
      sub-cellular fraction is the site for the synthesis of phosphatidylcholine, which
      in seeds is synthesized from diacylglycerol by CDP-choline: diacylglycerol
      cholinephosphotransferase. In microsomes from Cuphea lanceolata, a plant that
      accumulates fatty acids with 10 carbons and no double bonds (10:0) in its oil,
      the diacylglycerol acyltransferase exhibited 4-fold higher activity with
      10:0/10:0 molecular species of diacylglycerol than with molecular species
      containing 18-carbon fatty acids. In castor bean (Ricinus communis), which
      accumulates oil containing ricinoleic acid, diricinoleoyldiacylglycerol was the
      favored substrate for triacylglycerol synthesis. In contrast to these modest
      specificities of the diacylglycerol acyltransferases, the
      cholinephosphotransferases from these plants and from safflower (Carthamus
      tinctorius) and rapeseed (Brassica napus) showed little or no specificity across
      a range of different diacylglycerol substrates. Consideration of these results
      and other data suggests that the targeting of unusual fatty acids to
      triacylglycerol synthesis and their exclusion from membrane lipids are not
      achieved on the basis of the diacylglycerol substrate specificities of the
      enzymes involved and may instead require the spatial separation of two different
      diacylglycerol pools.

PMID- 12226232
TI  - Fusicoccin Binding to Its Plasma Membrane Receptor and the Activation of the
      Plasma Membrane H+-ATPase (III. Is There a Direct Interaction between the
      Fusicoccin Receptor and the Plasma Membrane H+-ATPase?).
AB  - A radioimmunoassay using antibodies raised against bovine serum albumin
      conjugated fusicoccin (FC) was applied to measure FC bound to the plasma membrane
      (PM) isolated from seedlings of radish (Raphanus sativus L.) and of Arabidopsis
      thaliana treated in vivo plus or minus the toxin. FC bound to the PM from
      seedlings treated with 5 [mu]M FC was 2-fold (radish) to 7-fold (A. thaliana)
      higher than the binding capacity of control PM. FC binding depended on the
      duration of the in vivo treatment but was unaffected by cycloheximide. When FC
      binding and the PM H+-ATPase activity were compared under different conditions
      (in vivo or in vitro treatment of different lengths or with different
      concentrations of FC), a strict linear relation between FC binding and the
      activation of the PM H+-ATPase was observed in both plant materials under all the
      conditions tested. Comparison between the maximum binding capacity and the amount
      of H+-ATPase observed in PM from the two plant materials suggest a one-to-one
      stoichiometry between the FC receptor and the PM H+-ATPase.

PMID- 12226233
TI  - Auxins and Cytokinins as Antipodal Modulators of Elasticity within the Actin
      Network of Plant Cells.
AB  - The cytoskeleton of plant and animal cells serves as a transmitter, transducer,
      and effector of cell signaling mechanisms. In plants, pathways for proliferation,
      differentiation, intracellular vesicular transport, cell-wall biosynthesis,
      symbiosis, secretion, and membrane recycling depend on the organization and
      dynamic properties of actin- and tubulin-based structures that are either
      associated with the plasma membrane or traverse the cytoplasm. Recently, a new in
      vivo cytoskeletal assay (cell optical displacement assay) was introduced to
      measure the tension within subdomains (cortical, transvacuolar, and perinuclear)
      of the actin network in living plant cells. Cell optical displacement assay
      measurements within soybean (Glycine max [L.]) root cells previously demonstrated
      that lipophilic signals, e.g. linoleic acid and arachidonic acid or changes in
      cytoplasmic pH gradients, could induce significant reductions in the tension
      within the actin network of transvacuolar strands. In contrast, enhancement of
      cytoplasmic free Ca2+ resulted in an increase in tension. In the present
      communication we have used these measurements to show that a similar antipodal
      pattern of activity exists for auxins and cytokinins (in their ability to modify
      the tension within the actin network of plant cells). It is suggested that these
      growth substances exert their effect on the cytoskeleton through the activation
      of signaling cascades, which result in the production of lipophilic and ionic
      second messengers, both of which have been demonstrated to directly effect the
      tension within the actin network of soybean root cells.

PMID- 12226234
TI  - Effect of Salt Stress on Germin Gene Expression in Barley Roots.
AB  - Germin gene expression in barley (Hordeum vulgare L.) seedlings responds to
      developmental and environmental cues. During seed germination, germin mRNA levels
      were maximal 2 d after the start of imbibition in control seedlings and declined
      to low levels by 6 d. When seeds were sown in the presence of 200 mM NaCl, germin
      mRNA levels were also maximal after 2 d, but NaCl treatment, which slowed
      seedling growth, prolonged germin gene expression for an additional 1 d. In 4-d
      old seedlings, germin mRNA levels were highest in roots and higher in the
      vascular transition region than in shoots. In roots of 6-d-old seedlings, germin
      gene expression was regulated by salt shock and plant growth regulators. Induced
      germin mRNA levels were maximal 8 h after treatment with NaCl, salicylate, methyl
      salicylate, or methyl jasmonate and 4 h after treatment with abscisic acid and
      indoleacetic acid. Like germin mRNA, dehydrin mRNA levels were maximal 8 h after
      NaCl treatment. In contrast, peroxidase mRNA levels declined to less than control
      levels within 30 min of treatment. Germin gene expression is regulated
      developmentally by salt stress and by treatments with plant hormones. Since
      germin is an oxalate oxidase, these result imply that oxalate has important roles
      in plant development and homeostasis.

PMID- 12226235
TI  - Activation of Phospholipase A by Plant Defense Elicitors.
AB  - Participation of phospholipase A (PLase A) in plant signal transduction has been
      documented for auxin stimulation of growth but not for elicitation of any plant
      defense response. In this paper, we report two independent assays for monitoring
      PLase A induction in plant cells and have used these assays to evaluate whether
      transduction of defense-related signals might require PLase A activation.
      Oligogalacturonic acid, a potent elicitor of the soybean (Glycine max) H2O2
      burst, was unable to stimulate endogenous PLase A, suggesting that PLase A
      activation is not an obligate intermediate in the oligogalacturonic acid-induced
      burst pathway. In contrast, harpin and an extract from the pathogenic fungus
      Verticillium dahliae both stimulated the oxidative burst and promoted a rapid
      increase in PLase A activity. To evaluate the possible role of this inducible
      PLase A activity in transducing the oxidative burst, we tested the effect of
      chlorpromazine-HCl, a PLase A inhibitor on elicitor-stimulated burst activity.
      Pretreatment with chloropromazine was found to inhibit the H2O2 burst triggered
      by V. dahliae extract at the same concentration at which it blocked PLase A
      activation. In contrast, neither the harpin- nor oligogalacturonic acid-induced
      burst was altered by addition of chlorpromazine. These data suggest that PLase A
      stimulation may be important in certain elicitor-induced oxidative bursts (e.g.
      V. dahliae) and that other elicitors such as oligogalacturonic acid and harpin
      must operate through independent signaling intermediates to activate the same
      defense response.

PMID- 12226236
TI  - Abscisic Acid-Induced Phosphoinositide Turnover in Guard Cell Protoplasts of
      Vicia faba.
AB  - Guard cell protoplasts of Vicia faba treated with 10 [mu]M (+)abscisic acid (ABA)
      in the light exhibited a 20% decrease in diameter within 1.5 h, from 24.1 to 19.6
      [mu]m. Within 10 s of administration of ABA, a 90% increase in levels of inositol
      1,4,5-trisphosphate was observed, provided that cells were treated with Li+, an
      inhibitor of inositol phosphatase activity, prior to incubation. Concomitantly,
      levels of 32P-labeled phosphatidylinositol 4,5-bisphosphate and
      phosphatidylinositol 4-phosphate decreased 20% compared to levels in control
      cells; levels of label in the membrane lipids phosphatidylcholine,
      phosphatidylethanolamine, and phosphatidylglycerol did not change significantly
      in response to ABA treatment. These results show that phosphoinositide turnover
      is activated in response to ABA in guard cells. We conclude that phosphoinositide
      signaling is likely to be a step in the biochemical cascade that couples ABA to
      guard cell shrinking and stomatal closure.

PMID- 12226237
TI  - Osmoregulation by Oat Coleoptile Protoplasts (Effect of Auxin).
AB  - The effect of auxin on the physiology of protoplasts from growing oat (Avena
      sativa L.) coleoptiles was investigated. Protoplasts, isolated iso-osmotically
      from peeled oat coleoptile segments, were found to swell steadily over many
      hours. Incubated in 1 mM CaCl2, 10 mM KCl, 10 mM 2-(morpholino)ethanesulfonic
      acid/1,3-bis-[tris(hydroxymethyl)methylamino]propane, pH 6.5, and mannitol to 300
      milliosmolal, protoplasts swelled 28.9% [plus or minus] 2.0 (standard error)
      after 6 h. Addition of 10 [mu]M indoleacetic acid (IAA) increased swelling to
      41.1% [plus or minus] 2.1 (standard error) after 6 h. Swelling (in the absence of
      IAA) was partially dependent on K+ in the bath medium, whereas auxin-induced
      swelling was entirely dependent on K+. Replacement of mannitol in the bath by Glc
      increased swelling (in the absence of IAA) and eliminated auxin-induced swelling.
      Swelling with or without IAA was inhibited by osmotic shock and was completely
      reversed by 0.1 mM NaN3. Sodium orthovanadate, applied at 0.5 mM, only gradually
      inhibited swelling under various conditions but was most effective with
      protoplasts prepared from tissue preincubated in vanadate. Our data are
      interpreted to suggest that IAA increases the conductance of the plasma membrane
      to K+.

PMID- 12226238
TI  - Two Chains of Rhamnogalacturonan II Are Cross-Linked by Borate-Diol Ester Bonds
      in Higher Plant Cell Walls.
AB  - Polysaccharide moiety of the boron-polysaccharide complex (T. Matoh, K. Ishigaki,
      K. Ohno, J. Azuma [1993] Plant Cell Physiol 34: 639-642) isolated from radish
      (Raphanus sativus) roots has been shown to be rhamnogalacturonan II by glycosyl
      linkage analysis and the presence of diagnostic monosaccharides, including
      apiose, aceric acid, 2-O-methylfucose, and 3-deoxy-D-manno-2-octulosonic acid.
      Removal of boron from the complex reduced the molecular weight by one-half
      without causing a significant increase in the number of reducing end groups,
      indicating that boron, as boric acid, links two rhamnogalacturonan II chains
      together to form the boron-polysaccharide complex.

PMID- 12226239
TI  - Genetic Dissection of the Relative Roles of Auxin and Gibberellin in the
      Regulation of Stem Elongation in Intact Light-Grown Peas.
AB  - Exogenous gibberellin (GA) and auxin (indoleacetic acid [IAA]) strongly
      stimulated stem elongation in dwarf GA1-deficient le mutants of light-grown pea
      (Pisum sativum L.): IAA elicited a sharp increase in growth rate after 20 min
      followed by a slow decline; the GA response had a longer lag (3 h) and growth
      increased gradually with time. These responses were additive. The effect of GA
      was mainly in internodes less than 25% expanded, whereas that of IAA was in the
      older, elongating internodes. IAA stimulated growth by cell extension; GA
      stimulated growth by an increase in cell length and cell number. Dwarf lkb GA
      response-mutant plants elongated poorly in response to GA (accounted for by an
      increase in cell number) but were very responsive to IAA. GA produced a
      substantial elongation in lkb plants only in the presence of IAA. Because lkb
      plants contain low levels of IAA, growth suppression in dwarf lkb mutants seems
      to be due to a deficiency in endogenous auxin. GA may enhance the auxin induction
      of cell elongation but cannot promote elongation in the absence of auxin. The
      effect of GA may, in part, be mediated by auxin. Auxin and GA control separate
      processes that together contribute to stem elongation. A deficiency in either
      leads to a dwarfed phenotype.

PMID- 12226240
TI  - Genetically Engineered Plants Resistant to Soil Drying and Salt Stress: How to
      Interpret Osmotic Relations?

PMID- 12226242
TI  - The Tissue-Specific Expression of a Tobacco Phytochrome B Gene.
AB  - We have isolated a genomic clone from Nicotiana tabacum, designated Nt-PHYB-1,
      encoding a type-II, "green tissue" phytochrome apoprotein. Recombinant genes,
      consisting of the 3319-bp promoter of the Nt-PHYB-1 gene (including the entire
      5[prime] untranslated sequence but not the ATG) or its deletion derivatives and
      the bacterial [beta]-glucuronidase reporter gene, were constructed and
      transferred into tobacco. The expression patterns and levels of the endogenous Nt
      PHYB-1, as well as those of the transgenes, were determined by RNase protection
      assays and by [beta]-glucuronidase histochemical staining. We show that (a) the
      PHYB-1 gene has three transcription start sites, (b) the abundance of the three
      PHYB-1-specific mRNAs is different, and that (c) it is not regulated by light.
      However, we do demonstrate that transcription of the endogenous PHYB-1 gene and
      that of the recombinant genes exhibit a well-defined organ and tissue
      specificity. This tobacco PHYB gene is relatively highly expressed in leaf, stem,
      and different floral organs but not in root. Deletion analysis of the Nt-PHYB-1
      promoter indicates that a 382-bp region, located between -1472 and -1089, is
      required for high-level expression of this gene.

PMID- 12226243
TI  - Subcellular Visualization of Gene Transcripts Encoding Key Proteins of the
      Chlorophyll Accumulation Process in Developing Chloroplasts.
AB  - The coordination of the synthesis of chlorophyll (Chl) and light-harvesting Chl
      proteins was determined by observing the sequence of appearance of the specific
      mRNAs for the nuclear genes CHLH, Por, and Lhcb1*2 (AB180). CHLH encodes a
      magnesium protoporphyrin chelatase subunit that is involved in the first
      committed step in Chl biosynthesis; Por encodes protochlorophyllide
      oxidoreductase, which catalyzes the penultimate and only light-dependent step in
      Chl biosynthesis; and Lhcb1*2 encodes light-harvesting Chl a/b binding protein of
      the type-1 light-harvesting complex of photosystem II. Using digoxigenin-labeled
      antisense and sense RNA probes and a highly sensitive in situ hybridization
      technique, we have visualized the first appearance of the specific mRNAs in
      postmitotic mesophyll cells of developing 7-d-old wheat leaves (Triticum aestivum
      cv Maris dove). The transcripts for CHLH and POR are detectable in the youngest
      (18 h postmitotic) leaf tissue containing dividing cells; light-harvesting
      complex of photosystem II transcripts appear 12 h later. This is consistent with
      a requirement for accumulation of Chl before synthesis of Chl a/b binding protein
      can proceed at a high rate. All of the transcripts are most abundant in mesophyll
      cells. In the first leaf the POR message is initially restricted to the palisade,
      but 12 h later it is also present in the spongy mesophyll cells. All three
      transcripts aggregated around the surface of the chloroplasts, suggesting that
      translation may occur preferentially in the vicinity of the target organelle for
      the primary translation products.

PMID- 12226244
TI  - The Competence of Maize Shoot Meristems for Integrative Transformation and
      Inherited Expression of Transgenes.
AB  - We have developed a novel and reproducible system for recovery of fertile
      transgenic maize (Zea mays L.) plants. The transformation was performed using
      microprojectile bombardment of cultured shoot apices of maize with a plasmid
      carrying two linked genes, the Streptomyces hygroscopicus phosphinothricin
      acetyltransferase gene (bar) and the potato proteinase inhibitor II gene, either
      alone or in combination with another plasmid containing the 5[prime] region of
      the rice actin 1 gene fused to the Escherichia coli [beta]-glucuronidase gene
      (gus). Bombarded shoot apices were subsequently multiplied and selected under 3
      to 5 mg/L glufosinate ammonium. Co-transformation frequency was 100% (146/146)
      for linked genes and 80% (41/51) for unlinked genes. Co-expression frequency of
      the bar and gus genes was 57% (29/51). The co-integration, co-inheritance, and co
      expression of bar, the potato proteinase inhibitor II gene, and gus in transgenic
      R0, R1, and R2 plants were confirmed. Localized expression of the actin 1-GUS
      protein in the R0 and R1 plants was extensively analyzed by histochemical and
      fluorometric assays.

PMID- 12226245
TI  - Hormonal Studies of fass, an Arabidopsis Mutant That Is Altered in Organ
      Elongation.
AB  - We have isolated an allele of fass, an Arabidopsis thaliana mutation that
      separates plant development and organ differentiation from plant elongation, and
      studied its hormonal regulation. Micro-surgically isolated fass roots elongate
      2.5 times as much as the roots on intact mutant plants. Wild-type heart embryos,
      when cultured with a strong auxin, naphthaleneacetic acid, phenocopy fass
      embryos. fass seedlings contain variable levels of free auxin, which average 2.5
      times higher than wild-type seedling levels, and fass seedlings evolve 3 times as
      much ethylene as wild-type seedlings on a per-plant basis over a 24-h period. The
      length-to-width ratios of fass seedlings can be changed by several compounds that
      affect their endogenous ethylene levels, but fass is epistatic to etr1, an
      ethylene-insensitive mutant. fass's high levels of free auxin may be inducing its
      high levels of ethylene, which may, in turn, result in the fass phenotype. We
      postulate that FASS may be acting as a negative regulator to maintain wild-type
      auxin levels and that the mutation may be in an auxin-conjugating enzyme.

PMID- 12226246
TI  - Signaling in Soybean Phenylpropanoid Responses (Dissection of Primary, Secondary,
      and Conditioning Effects of Light, Wounding, and Elicitor Treatments).
AB  - The spatial and temporal deployment of plant defense responses involves a complex
      interplay of signal events, often resulting in superimposition of signaling
      processes. We have employed a minimal-wound protocol to clearly separate and
      characterize the specific contributions of light, wounding, and a wall glucan
      elicitor preparation (PWG) from Phytophthora sojae (Kauf. and Gerde.) to the
      regulation of phenylpropanoid defense responses in soybean (Glycine max L.
      [Merr.]) cotyledon tissues. The assay also allowed us to clearly reconstitute
      responses to combinations of these primary signals and to examine the effects of
      other pathogenesis-related molecules on the responses in a defined manner. Light
      specifically triggers accumulation of malonylglucosyl conjugates of the 5-hydroxy
      isoflavone, genistein, which is normally found in epidermal cells. PWG
      selectively induces accumulation of conjugates of the 5-deoxy-isoflavone
      daidzein, the first committed precursor of the phytoalexin glyceollin. Wounding
      initiates phenolic polymer deposition, a process greatly potentiated by PWG and
      light. Whereas glutathione selectively enhances light induction of genistein
      conjugates, methyl jasmonate enhances both light and PWG-induced isoflavone
      conjugate accumulations. Wound exudate fully activates the cell's capacity
      (competency) for the phenolic polymer and glyceollin responses to PWG, whereas
      glutathione partially restores competency, favoring coumestrol and phenolic
      polymer responses to PWG. Abscisic acid inhibits all induced phenylpropanoid
      responses.

PMID- 12226247
TI  - Vicilin and Napin Storage-Protein Gene Promoters Are Responsive to Abscisic Acid
      in Developing Transgenic Tobacco Seed but Lose Sensitivity following Premature
      Desiccation.
AB  - In transgenic tobacco (Nicotiana tabacum L.) seed, expression of chimeric [beta]
      glucuronidase (GUS) genes containing the vicilin or napin storage-protein gene
      promoters is responsive to premature drying and declines upon rehydration (L.
      Jiang, W.L. Downing, C.L. Baszczynski, A.R. Kermode [1995] Plant Physiol 107:
      1439-1449). Desiccation may cause changes in the content of or sensitivity to
      abscisic acid (ABA), partially or wholly removing the effects of this "modulator"
      of developmental gene expression. We studied the enhancement of GUS reporter
      enzyme activities in transgenic tobacco by exogenous ABA before and after drying.
      A racemic mixture of ABA at 10 [mu]M caused a 2- to 3-fold increase in GUS
      activity in developing transgenic seed expressing chimeric genes containing the
      vicilin or napin gene promoters. However, when these seeds were prematurely dried
      prior to their culture on ABA medium, enhancement of GUS activity was virtually
      abolished. Use of optically pure ABAs revealed that the enhancement in GUS
      activity in developing fresh seed was due largely to the natural (+) form of ABA.
      Chimeric constructs containing a viral 35S promoter did not respond to ABA
      whether or not premature drying was applied. Thus, vicilin and napin chimeric
      genes, initially sensitive to ABA, become relatively insensitive to the hormone
      following drying. A decline in ABA sensitivity may be an important factor in the
      cessation of storage-protein gene expression.

PMID- 12226248
TI  - The Composition of Metals Bound to Class III Metallothionein (Phytochelatin and
      Its Desglycyl Peptide) Induced by Various Metals in Root Cultures of Rubia
      tinctorum.
AB  - The induction of phytochelatins (PCs) and their desglycyl peptides (both are
      referred to as class III metallothionein [CIIIMT]) by exposure to various metals
      (Ag+, As3+, As5+, Cd2+, Cu2+, Ga3+, Hg2+, In3+, Ni2+, Pb2+, Pd2+, Se4+, and Zn2+)
      and the metal composition in the CIIIMTs were investigated in root cultures of
      Rubia tinctorum L. All of these metal species induced PCs to various degrees when
      analyzed by the postcolumn derivatization high-performance liquid chromatography
      method. The desglycyl peptides of PCs often were also present. However, only Ag,
      Cd, and Cu were bound to the CIIIMTs that they induced when analyzed by the high
      performance liquid chromatography-inductively coupled plasma-atomic emission
      spectrometry method. Cu was also bound to the CIIIMTs induced by Ag+, As3+, and
      Cd2+. After Ag+ exposure, an Fe peak that may be of Fe-CIIIMT was also observed.
      However, most of the metal species studied were not bound to the CIIIMTs that
      they induced.

PMID- 12226249
TI  - Distribution and Redistribution of Sulfur Supplied as [35S]Sulfate to Roots
      during Vegetative Growth of Soybean.
AB  - Soybean (Glycine max L.) plants were grown in nutrient solution containing 10
      [mu]M sulfate and were treated at various times with [35S]sulfate for 48 h.
      Growth was then continued in unlabeled solution. The sulfur content of each leaf
      increased rapidly until it was about 40% expanded; small, additional increases
      occurred until the leaf was about 70% expanded after which the sulfur content
      decreased by about 50%. Leaves that were about 60 to 70% expanded during the
      pulse were strongly labeled but then underwent a significant loss of 35S label.
      Leaves that were in the early stages of expansion imported little 35S label
      during the pulse but acquired 35S label during the chase period as they expanded
      (i.e. redistribution). Most of the redistributed 35S label was derived from other
      leaves. The rates of both sulfur import and sulfur export by a leaf were greatest
      at about 70% expansion. Leaves that acquired 35S label during early development
      retained a much higher proportion of their label than leaves that were more
      developed, suggesting that the sulfur acquired by leaves during early development
      is preferentially incorporated into a pool that is less mobile than the sulfur
      acquired in the later stages of leaf growth.

PMID- 12226250
TI  - Purification and Characterization of the Enzymes of Fructan Biosynthesis in
      Tubers of Helianthus tuberosus Colombia (II. Purification of Sucrose:Sucrose 1
      Fructosyltransferase and Reconstitution of Fructan Synthesis in Vitro with
      Purified Sucrose:Sucrose 1-Fructosyltransferase and Fructan:Fructan 1
      Fructosyltransferase).
AB  - Sucrose:sucrose 1-fructosyltransferase (1-SST), an enzyme involved in fructan
      biosynthesis, was purified to homogeneity from tubers of Helianthus tuberosus
      that were harvested in the accumulation phase. Gel filtration under native
      conditions predicted a molecular mass of about 67 kD. Electrophoresis or gel
      filtration under denaturing conditions yielded a 27- and a 55-kD fragment. 1-SST
      preferentially catalyzed the conversion of sucrose into the trisaccharide 1
      kestose (GF2). Other reactions catalyzed by 1-SST at a lower rate were self
      transfructosylations with GF2 and 1,1-nystose (GF3) as substrates yielding GF3
      and 1,1,1-fructosylnystose, respectively, as products. 1-SST also catalyzed the
      removal of the terminal fructosyl unit from both GF2 and GF3, which resulted in
      the release of sucrose and GF2, respectively, and free Fru. The purified enzyme
      did not display [beta]-fructosidase activity. An enzyme mixture of purified 1-SST
      and fructan:fructan 1-fructosyltransferase, both isolated from tubers, was able
      to synthesize fructans up to a degree of polymerization of at least 13 with
      sucrose as a sole substrate.

PMID- 12226251
TI  - N4-Hexanoylspermidine, a New Polyamine-Related Compound That Accumulates during
      Ovary and Petal Senescence in Pea.
AB  - A previously unknown polyamine conjugate that accumulates in senescing ovaries of
      pea (Pisum sativum L.) was shown by mass spectrometry, nuclear magnetic
      resonance, and chemical synthesis to be N4-hexanoylspermidine (hexanoyl-spd) This
      structure was indicated by analysis of the dansylated polyamine using fast atom
      bombardment mass spectrometry, following purification by high-performance liquid
      chromatography. Furthermore, acid hydrolysis of the compound yielded spermidine
      and hexanoic acid. 1H-nuclear magnetic resonance suggested that spermidine was
      substituted at N4 in the conjugate. Hexanoyl-spd was synthesized, and its
      didansyl derivative was shown to have an identical mass spectrum and high
      performance liquid chromatography retention time as the derivatized natural
      compound. Further confirmation of its structure was obtained by comparison of the
      synthetic and natural polyamines as trifluoroacetyl derivatives using gas
      chromatography-mass spectrometry. This new polyamine conjugate is present in pea
      ovaries at low levels at anthesis and its concentration remains low in developing
      seeded fruit or in parthenocarpic fruit that have been induced by application of
      growth regulators to emasculated flowers or by topping the plant. Conjugate
      levels are also low in parthenocarpic fruit induced naturally in the slender (la
      crys) mutant. However, levels of hexanoyl-spd increase progressively in senescing
      petals and ovaries, beginning at anthesis or 2 d later, respectively.

PMID- 12226252
TI  - Involvement of Activated Oxygen in Nitrate-Induced Senescence of Pea Root
      Nodules.
AB  - The effect of short-term nitrate application (10 mM, 0-4 d) on nitrogenase
      (N2ase) activity, antioxidant defenses, and related parameters was investigated
      in pea (Pisum sativum L. cv Frilene) nodules. The response of nodules to nitrate
      comprised two stages. In the first stage (0-2 d), there were major decreases in
      N2ase activity and N2ase-linked respiration and concomitant increases in carbon
      cost of N2ase and oxygen diffusion resistance of nodules. There was no apparent
      oxidative damage, and the decline in N2ase activity was, to a certain extent,
      reversible. The second stage (>2 d) was typical of a senescent, essentially
      irreversible process. It was characterized by moderate increases in oxidized
      proteins and catalytic Fe and by major decreases in antioxidant enzymes and
      metabolites. The restriction in oxygen supply to bacteroids may explain the
      initial decline in N2ase activity. The decrease in antioxidant protection is not
      involved in this process and is not specifically caused by nitrate, since it also
      occurs with drought stress. However, comparison of nitrate- and drought-induced
      senescence shows an important difference: there is no lipid degradation or lipid
      peroxide accumulation with nitrate, indicating that lipid peroxidation is not
      necessarily involved in nodule senescence.

PMID- 12226253
TI  - Reversible Inhibition of Tomato Fruit Gene Expression at High Temperature
      (Effects on Tomato Fruit Ripening).
AB  - The reversible inhibition of three ripening-related processes by high-temperature
      treatment (38[deg]C) was examined in tomato (Lycopersicon esculentum L. cv
      Daniella) fruit. Ethylene production, color development, and softening were
      inhibited during heating and recovered afterward, whether recovery took place at
      20[deg]C or fruit were first held at chilling temperature (2[deg]C) after heating
      and then placed at 20[deg]C. Ethylene production and color development proceeded
      normally in heated fruit after 14 d of chilling, whereas the unheated fruit had
      delayed ethylene production and uneven color development. Levels of mRNA for 1
      aminocyclopropane-1-carboxylic acid oxidase, phytoene synthase, and
      polygalacturonase decreased dramatically during the heat treatment but recovered
      afterward, whereas the mRNA for HSP17 increased during the high-temperature
      treatment and then decreased when fruit were removed from heat. As monitored by
      western blots, the HSP17 protein disappeared from fruit tissue after 3 d at
      20[deg]C but remained when fruit were held at 2[deg]C. The persistence of heat
      shock proteins at low temperature may be relevant to the protection against
      chilling injury provided by the heat treatment. Protein levels of 1
      aminocyclopropane-1-carboxylic acid oxidase and polygalacturonase also did not
      closely follow the changes in their respective mRNAs. This implied both
      differences in relative stability and turnover rates of mRNA compared to protein
      and nontranslation of the message that accumulated in low temperature. The
      results suggest that high temperature inhibits ripening by inhibiting the
      accumulation of ripening-related mRNAs. Ripening processes that depend on
      continuous protein synthesis including ethylene production, lycopene
      accumulation, and cell-wall dissolution are thereby diminished.

PMID- 12226254
TI  - Characterization of a Mutant of Chlamydomonas reinhardtii That Uses L-Methionine
      S-Sulfoximine and Phosphinothricin as Nitrogen Sources for Growth.
AB  - A strain of Chlamydomonas reinhardtii, named ARF-1, which grows with the
      glutamine synthetase (GS) inhibitor L-methionine-S-sulfoximine (MSX), has been
      isolated and characterized. Mutant ARF-1 is affected at a single and dominant
      gene, tentatively assigned to the allele msr-1-2. Neither the uptake of ammonia
      nor the two GS isoenzyme activities of the mutant were affected by MSX in vivo.
      GS activities, however, were fully abolished in vitro, thus suggesting that
      neither GS isoform was an altered enzyme resistant to the inhibitor. Resistance
      to MSX does not seem to be due to either a defect in a permease responsible for
      the transport of MSX or over-expression of GS activity, nor did we find an
      alternative enzymatic pathway for the assimilation of ammonium. Resistance was
      independent of the nitrogen source used and was strongly enhanced by the addition
      of acetate. Unlike the parental strain, mutant ARF-1 can degrade and utilize MSX
      as the sole nitrogen source for growth, which could account for the observed
      resistance. Thus, this mutant can be classified as a novel type of MSX-resistant
      mutant. This mutant can also use phosphinothricin, methionine sulfone, or
      methionine sulfoxide as the sole sources of nitrogen. This capability
      cosegregated in the genetic crosses and was also observed in all the diploids
      isolated. An MSX/[alpha]-ketoglutarate aminotransferase activity, not present in
      the parental strain 305, was detected in mutant ARF-1 cells. Therefore, we
      propose that the locus msr-1-2 either codes for this transaminase activity or its
      product gene is necessary to express this transaminase activity.

PMID- 12226255
TI  - Evidence That Isolated Chloroplasts Contain an Integrated Lipid-Synthesizing
      Assembly That Channels Acetate into Long-Chain Fatty Acids.
AB  - High rates of light-dependent fatty acid synthesis from acetate were measured in
      isolated chloroplasts that were permeabilized to varying extents by resuspension
      in hypotonic reaction medium. The reactions in hypotonic medium unsupplemented
      with cofactors were linear with time and were directly proportional to
      chlorophyll concentration, suggesting that the enzymes and cofactors of fatty
      acid synthesis remained tightly integrated and thylakoid associated within
      disrupted chloroplasts. Permeabilized chloroplasts expanded to at least twice the
      volume of intact chloroplasts, lost about 50% of their stromal proteins in the
      medium, and metabolized exogenous nucleotides. However, neither acetyl-coenzyme A
      (CoA) nor malonyl-CoA inhibited fatty acid synthesis from acetate; nor were [1
      14C]acetyl-CoA and [14C]malonyl-CoA significantly incorporated into fatty acids.
      Fatty acid synthesis from acetate was independent of added cofactors but was
      totally light dependent. Changes in the products of fatty acid synthesis were
      consistent with the loss of endogenous glycerol-3-phosphate from permeabilized
      chloroplasts. However, in appropriately supplemented medium, the products of
      acetate incorporation by spinach (Spinacia oleracea) chloroplasts were similar
      when reactions were carried out in either isotonic or hypotonic medium. Taken
      together, the results of this study suggest that the enzymes of fatty acid
      synthesis with chloroplasts are organized into a multienzyme assembly that
      channels acetate into long-chain fatty acids, glycerides, and CoA esters.

PMID- 12226256
TI  - Effects of Boron on Rhizobium-Legume Cell-Surface Interactions and Nodule
      Development.
AB  - Boron (B) is an essential micronutrient for the development of nitrogen-fixing
      root nodules in pea (Pisum sativum). By using monoclonal antibodies that
      recognize specific glycoconjugate components implicated in legume root-nodule
      development, we investigated the effects of low B on the formation of infection
      threads and the colonization of pea nodules by Rhizobium leguminosarum bv viciae.
      In B-deficient nodules the proportion of infected host cells was much lower than
      in nodules from plants supplied with normal quantities of B. Moreover, the host
      cells often developed enlarged and abnormally shaped infection threads that
      frequently burst, releasing bacteria into damaged host cells. There was also an
      over-production of plant matrix material in which the rhizobial cells were
      embedded during their progression through the infection thread. Furthermore, in a
      series of in vitro binding studies, we demonstrated that the presence of B can
      change the affinity with which the bacterial cell surface interacts with the
      peribacteroid membrane glycocalyx relative to its interaction with intercellular
      plant matrix glycoprotein. From these observations we suggest that B plays an
      important role in mediating cell-surface interactions that lead to endocytosis of
      rhizobia by host cells and hence to the correct establishment of the symbiosis
      between pea and Rhizobium.

PMID- 12226258
TI  - Transcriptional and Posttranscriptional Regulation of Dormancy-Associated Gene
      Expression by Afterripening in Wild Oat.
AB  - To investigate whether the afterripening-induced changes in gene expression are
      at the transcriptional or posttranscriptional level in wild oat (Avena fatua)
      seeds, we chose four dormancy-associated genes to estimate their relative
      transcription activities and the stability of their corresponding transcripts in
      afterripened and dormant embryos. The transcription activities for those genes
      were 1.5 to 7 times higher in dormant embryos than in afterripened embryos 24 h
      after incubation, as determined by nuclear run-on assays. The half-lives of the
      transcripts in afterripened and dormant embryos were estimated by the use of
      actinomycin D. The application of actinomycin D resulted in the stabilization of
      the transcripts. Nevertheless, the results indicated that the half-lives of the
      transcripts were much greater in dormant embryos than in afterripened embryos.
      Considering the great differences in the steady-state levels and the half-lives
      of the mRNAs, and the relatively small differences in transcription activities of
      the genes between afterripened and dormant embryos, we conclude that
      afterripening regulates the expression of dormancy-associated genes in excised
      embryos mainly at the posttranscriptional level and that transcriptional control
      plays a minor role.

PMID- 12226257
TI  - A Complex Array of Proteins Related to the Multimeric Leucine Aminopeptidase of
      Tomato.
AB  - Leucine aminopeptidase (LAP) mRNAs are induced in response to mechanical
      wounding, pathogen infection, and insect infestation (V. Pautot, F.M. Holzer, B.
      Reisch, L.L. Walling [1993] Proc Natl Acad Sci USA 90: 9906-9910). Polyclonal
      antibodies to a glutathione S-transferase-LAP fusion protein and affinity
      purified antibodies recognizing LAP antigenic determinants detected four classes
      of polypeptides in tomato (Lycopersicon esculentum) leaves. All four classes had
      multiple polypeptides in two-dimensional polyacrylamide gel electrophoresis
      immunoblots. Although antigenically related to the wound-induced tomato LAP
      proteins, the 77- and 66-kD LAP-like proteins accumulated in both healthy and
      wounded leaves. Two classes of 55-kD polypeptides with distinctive isoelectric
      points were designated as plant LAPs; only the acidic LAP proteins accumulated to
      high levels after mechanical wounding or Pseudomonas syringae pv tomato infection
      of tomato leaves. The temporal accumulation of LAP mRNAs was correlated with the
      increase in acidic LAP protein subunits. A slow-migrating LAP activity was
      detected using a native gel assay after wounding. The molecular mass of the
      native wound-induced LAP enzyme was 353 kD. The 55-kD acidic LAP proteins were
      associated with induced LAP activity, whereas the neutral LAPs and the LAP-like
      proteins were not associated with this exopeptidase. A second, fast-migrating
      aminopeptidase was detected in both healthy and wounded tomato leaves. Cell
      fractionation experiments revealed that wound-induced LAP is a soluble enzyme.

PMID- 12226259
TI  - Leaf-Mediated Light Responses in Petunia Flowers.
AB  - In the present work we studied the role of light in the regulation of flavonoid
      gene expression and anthocyanin synthesis in petunia (Petunia hybrida) corollas.
      We found that light is required for chalcone synthase gene (chs) expression,
      anthocyanin synthesis, and growth of detached and attached petunia corollas.
      Although direct illumination induced chs expression, pigmentation, and elongation
      of the detached corollas, irradiation of green leaves or sepals played the main
      role in the attached corollas. The duration, intensity, and spectrum of the light
      reaction suggest that phytochrome-mediated high-irradiance reactions are involved
      in the regulation of corolla development. Using the photosynthesis inhibitor 3
      (3,4-dichlorophenyl)-1,1-dimethylurea, we showed that photosynthesis does not
      significantly contribute to the leaf-mediated light responses. When sepals were
      removed or covered. [14C]sucrose up-take by the corolla of detached intact
      flowers was inhibited. The results of this study suggest that light is perceived
      by leaves and sepals and enhances corolla sink activity, elongation,
      pigmentation, and chs expression. The role of leaves and sepals in the light
      regulation of petunia corolla development is discussed.

PMID- 12226260
TI  - A New Screening Method for Algal Photosynthetic Mutants (CO2-Insensitive Mutants
      of the Green Alga Chlorella ellipsoidea).
AB  - A new method has been developed for screening algal photosynthetic mutants. This
      method uses autoradiography to assess gross photosynthetic 14C fixation by green
      algal colonies on agar plates and allows the identification of clones that differ
      in photosynthetic characteristics from wild-type cells. Three wild-type cells,
      high-CO2-grown Chlorella ellipsoidea, air-grown C. ellipsoidea, and air-grown
      Chlorella saccharophila, had K0.5 values for dissolved inorganic carbon (DIC) of
      1083, 250, and 50 [mu]M, respectively, and as plaques on agar plates at Chl
      densities greater than 25 [mu]g cm-2 exhibited relative amounts of 14C fixation
      of 15, 55, and 100%, respectively. Cells of C. ellipsoidea were mutagenized with
      x-rays and screened by this method. Growth of C. ellipsoidea in high CO2
      represses DIC transport and thus lowers its affinity for DIC. Five of the mutants
      detected by this method showed high-affinity photosynthesis similar to air-grown
      wild-type cells even when grown in high CO2. Seven other mutants when grown in
      high CO2 showed affinities for DIC intermediate between air-grown and high-CO2
      grown wild-type cells. The affinities of high-CO2-grown mutants were reflected
      precisely in their capacities to accumulate DIC intracellularly. These results
      indicate that the mutants are fully or partially insensitive to the repressive
      effect of ambient CO2 concentration on DIC transport.

PMID- 12226261
TI  - Chlorate as a Transport Analog for Nitrate Absorption by Roots of Tomato.
AB  - Several studies have indicated that chlorate (ClO3-) and nitrate (NO3-) may share
      a common transport system in higher plants. Here, we compared the interactions
      between ClO3- and NO3-uptake by roots of intact tomato (Lycopersicon esculentum
      cv T5) plants. Exposure to ClO3- for more than 2 h inhibited both net ClO3- and
      K+ uptake, presumably because of ClO3- toxicity; consequently, subsequent
      measurements were conducted after short exposures to ClO3-. The apparent affinity
      and apparent maximum rate of absorption for net ClO3- and NO3- uptake were very
      similar. Interactions between ClO3- and NO3- transport were complex; 50 [mu]M NO3
      acted as a mixed inhibitor of net ClO3- uptake, but 50 [mu]M ClO3- had no
      significant effect on net NO3- uptake, and 500 [mu]M ClO3- had no significant
      effect on 15NO3- influx. If the two ions share a single common high-affinity
      transport system, it is much more selective for NO3- than would be suggested by
      the similarity of net NO3- and ClO3- uptake kinetics. Our results indicate that,
      although NO3- may interfere with root ClO3- uptake, ClO3- is not a useful analog
      for the root high-affinity NO3- transport system.

PMID- 12226262
TI  - A Study of the Stationary Volumetric Elastic Modulus during Dehydration and
      Rehydration of Stems of Pea Seedlings.
AB  - The relationship between cortical-cell turgor pressure (P) and tissue water mass
      (W) was determined for stem segments of pea (Pisum sativum L.) seedlings
      subjected to hydration and dehydration. This allowed a test for elastic
      hysteresis in the cortical cells. The P-W curves for dehydration and hydration
      were not coincident. In some experiments, the P-W curves exhibited a "roll-off"
      at high P, similar to the "plateau effect" sometimes observed in pressure-chamber
      studies. When hydration was followed by a 4-h dehydration, the tissue water mass
      (W0) at minimum turgor was reduced. This might reflect a reduction in apoplastic
      water mass and/or a contraction of the symplast during dehydration. Neglecting
      the decrease in W0 leads to underestimates of the stationary volumetric elastic
      modulus ([epsilon]stat). The result of an analysis that assumes W0 was constant
      during hydration suggests that there was no significant difference in
      [epsilon]stat between dehydration and hydration and, hence, no significant
      elastic hysteresis. However, a 16-h dehydration increased [epsilon]stat; this
      might be a response to water stress.

PMID- 12226263
TI  - Evidence of the Photosynthetic Origin of Monoterpenes Emitted by Quercus ilex L.
      Leaves by 13C Labeling.
AB  - The carbon of the four main monoterpenes emitted by Quercus ilex L. leaves was
      completely labeled with 13C after a 20-min feeding with 99% 13CO2. This labeling
      time course is comparable with the labeling time course of isoprene, the
      terpenoid emitted by other Quercus species and synthesized in leaf chloroplasts.
      It is also comparable with that of phosphoglyceric acid. Our experiment therefore
      provides evidence that monoterpenes emitted by Q. ilex are formed from
      photosynthesis intermediates and may share the same synthetic pathway with
      isoprene. By analyzing the rate and the distribution of labeling in the different
      fragments, we looked for evidence of differential carbon labeling in the [alpha]
      pinene emitted. However, the labeling pattern was quite uniform in the different
      fragments, suggesting that the carbon skeleton of the emitted monoterpenes comes
      from a unique carbon source.

PMID- 12226264
TI  - Alternative Oxidase Activity and the Ubiquinone Redox Level in Soybean Cotyledon
      and Arum Spadix Mitochondria during NADH and Succinate Oxidation.
AB  - In Arum and soybean (Glycine max L.) mitochondria, the dependence of the
      alternative oxidase activity on the redox level of ubiquinone, with NADH and
      succinate as substrates, was studied, using a voltametric procedure to measure
      the ubiquinone redox poise in the mitochondrial membrane. The results showed that
      when the enzyme was activated by pyruvate the relationship between the
      alternative oxidase rate and the redox state of the ubiquinone pool was the same
      for both NADH and succinate oxidations. In the absence of pyruvate the
      alternative oxidase had an apparent lower affinity for ubiquinol. This was more
      marked with NADH than with succinate and was possibly due to pyruvate production
      during succinate oxidation or to an activation of the alternative oxidase by
      succinate itself. In Arum spadix (unlike soybean cotyledon) mitochondria,
      succinate oxidation via the alternative oxidase maintained the ubiquinone pool in
      a partially reduced state (60%), whereas NADH oxidation kept it almost completely
      reduced. Previous data comparing mitochondria from thermogenic and nonthermogenic
      tissues have not examined the full range of ubiquinone redox levels in both
      tissues, leading to the suggestion that the activity of alternative oxidase for
      Arum was different from nonthermogenic tissues. When the complete range of redox
      states of ubiquinone is used and the oxidase is fully activated, the alternative
      oxidase from thermogenic tissue (Arum) behaves similarly to that of
      nonthermogenic tissue (soybean).

PMID- 12226265
TI  - Specific Prenylation of Tomato Rab Proteins by Geranylgeranyl Type-II Transferase
      Requires a Conserved Cysteine-Cysteine Motif.
AB  - Posttranslational isoprenylation of some small GTP-binding proteins is required
      for their biological activity. Rab geranylgeranyl transferase (Rab GGTase) uses
      geranylgeranyl pyrophosphate to modify Rab proteins, its only known substrates.
      Geranylgeranylation of Rabs is believed to promote their association with target
      membranes and interaction with other proteins. Plants, like other eukaryotes,
      contain Rab-like proteins that are associated with intracellular membranes.
      However, to our knowledge, the geranylgeranylation of Rab proteins has not yet
      been characterized from any plant source. This report presents an activity assay
      that allows the characterization of prenylation of Rab-like proteins in vitro, by
      protein extracts prepared from plants. Tomato Rab1 proteins and mammalian Rab1a
      were modified by geranylgeranyl pyrophosphate but not by farnesyl pyrophosphate.
      This modification required a conserved cysteine-cysteine motif. A mutant form
      lacking the cysteine-cysteine motif could not be modified, but inhibited the
      geranylgeranylation of its wild-type homolog. The tomato Rab proteins were
      modified in vitro by protein extract prepared from yeast, but failed to become
      modified when the protein extract was prepared from a yeast strain containing a
      mutant allele for the [alpha] subunit of yeast Rab GGTase (bet4 ts). These
      results demonstrate that plant cells, like other eukaryotes, contain Rab GGTase
      like activity.

PMID- 12226266
TI  - Photosynthesis and Carbohydrate Partitioning for the C3 Desert Shrub Encelia
      farinosa under Current and Doubled CO2 Concentrations.
AB  - Changes in photosynthesis (A) and carbohydrate partitioning were studied for
      Encelia farinosa, a common C3 desert shrub in the southwestern United States,
      after a 3-month exposure to the current or a doubled CO2 concentration (750 [mu]L
      L-1). A remained unchanged under the current CO2 concentration but decreased
      during the day under the doubled CO2 concentration, resulting in a 46%
      enhancement in the early morning, 26% at midday, and 15% in the late afternoon by
      the elevated CO2. The decrease during the day under the doubled CO2 concentration
      may represent end-product inhibition, because the sucrose and the starch contents
      increased during the day proportionally more than under the current CO2
      concentration. The 14CO2 activity in sink leaves was maximal 3 h after labeling
      under the doubled and at 5 h under the current CO2 concentration, indicating
      faster movement of photosynthate out of source leaves and into sink tissues under
      the doubled CO2 concentration, which may have been responsible for the sustained
      enhancement in A under the doubled CO2 concentration.

PMID- 12226267
TI  - Involvement of Reactive Oxygen Species, Glutathione Metabolism, and Lipid
      Peroxidation in the Cf-Gene-Dependent Defense Response of Tomato Cotyledons
      Induced by Race-Specific Elicitors of Cladosporium fulvum.
AB  - The chronological order of responses to Cladosporium fulvum (Cooke) (Cf) race
      specific elicitors was assessed in cotyledons of three near-isogenic tomato
      (Lycopersicon esculentum Mill.) lines carrying either Cf-9 or Cf-2 or no Cf gene.
      The responses observed were dependent on the presence of a Cf gene, Avr-gene
      product dose injected, and the relative humidity (RH) of the growth chamber. At
      ambient RH, superoxide formation and lipid peroxidation occurred after 2 h (Cf9)
      and 4 h (Cf2). At elevated RH (98%) and at lower avirulence elicitor dose, Cf-Avr
      dependent lipid peroxidation was considerably attenuated. Significant electrolyte
      leakage occurred by 18 h but only at the lower RH. Total glutathione levels began
      to increase 2 to 4 h and 4 to 8 h after challenge of Cf9 and Cf2 cells,
      respectively, and by 48 h reached 665 and 570% of initial levels. A large
      proportion of this accumulation (87%) was as oxidized glutathione. When the RH
      was increased to 98%, increases in glutathione levels were strongly attenuated.
      Increased lipoxygenase enzyme activity was detected 8 h postchallenge in either
      incompatible interaction. These results indicate that the activation of the Cf
      Avr-mediated defense response results in severe oxidative stress.

PMID- 12226268
TI  - Race-Specific Elicitors of Cladosporium fulvum Induce Changes in Cell Morphology
      and the Synthesis of Ethylene and Salicylic Acid in Tomato Plants Carrying the
      Corresponding Cf Disease Resistance Gene.
AB  - Defense responses mediated by the genetically unlinked Cf-9 and Cf-2 genes were
      compared with those involving no Cf gene (Cf0). Compatible tomato (Lycopersicon
      esculentum)-Cladosporium fulvum intercellular washing fluids were injected into
      tomato cotyledons, and the kinetics of responses was monitored under conditions
      of 70 and 98% relative humidity. The latter conditions suppressed the normal
      macroscopic responses. For the Cf-9-Avr9 interaction, stomatal opening was
      induced within 3 to 4 h and after 9 h mesophyll cell death commenced. A burst of
      ethylene production occurred between 9 and 12.5 h and remained elevated. Free
      salicylic acid levels increased after 12 h, peaked at 24 h, and thereafter
      declined. For the Cf-2-Avr2 interaction, stomata became plugged after 8 h, and
      salicylic acid and ethylene levels increased by 12 and 18 h, respectively, and
      thereafter declined. Host cell death commenced around vascular tissue by 24 h.
      Cell death in both incompatible interactions was frequently preceded by cell
      enlargement. For Cf0-injected plants, no significant responses were detected.
      High humidity delayed and reduced the Cf-Avr-gene-dependent cell death and
      ethylene synthesis, whereas induced salicylic acid levels were unaffected for Cf
      2-Avr2 and reduced in magnitude only for Cf-9-Avr9.

PMID- 12226269
TI  - Possible Role of Cbr, an Algal Early-Light-Induced Protein, in Nonphotochemical
      Quenching of Chlorophyll Fluorescence.
AB  - The unicellular green alga Dunaliella bardawil exhibits typical responses to
      excessive light when starved for sulfate under normal light (60 [mu]E m-2 s-1)
      but not under low light (14 [mu]E m-2 s-1). Algae were analyzed during several
      days of sulfate starvation for nonphotochemical quenching of chlorophyll
      fluorescence in the absence or presence of the uncouplers SF-6847 (SF) or
      carbonyl cyanide p- trifluoromethoxyphenyl hydrazone. Parallel analyses followed
      two light-stress responses: (a) violaxanthin conversion to zeaxanthin and (b)
      accumulation of Cbr, a protein analogous to plant early-light-induced proteins
      and implicated in zeaxanthin binding. In cells starved under normal light SF
      inhibited nonphotochemical quenching during the first 24 h, but not from 40 h
      onward. In cells starved under low light SF inhibited nonphotochemical quenching
      throughout the starvation period. Under normal light accumulation of zeaxanthin
      was nearly maximal by 24 h, but Cbr was fully induced only by 40h. Under low
      light zeaxanthin accumulated slowly but no Cbr was evident. These results suggest
      that during exposure to excessive light, the initial pH gradient-dependent, Cbr
      independent mode of nonphotochemical quenching is modified to become less
      dependent on pH gradient and requires Cbr.

PMID- 12226270
TI  - Developmental and Tissue-Specific Structural Alterations of the Cell-Wall
      Polysaccharides of Arabidopsis thaliana Roots.
AB  - The plant cell wall is a dynamic structure that plays important roles in growth
      and development and in the interactions of plants with their environment and
      other organisms. We have used monoclonal antibodies that recognize different
      carbohydrate epitopes present in plant cell-wall polysaccharides to locate these
      epitopes in roots of developing Arabidopsis thaliana seedlings. An epitope in the
      pectic polysaccharide rhamnogalacturonan I is observed in the walls of epidermal
      and cortical cells in mature parts of the root. This epitope is inserted into the
      walls in a developmentally regulated manner. Initially, the epitope is observed
      in atrichoblasts and later appears in trichoblasts and simultaneously in cortical
      cells. A terminal [alpha]-fucosyl-containing epitope is present in almost all of
      the cell walls in the root. An arabinosylated (1->6)-[beta]-galactan epitope is
      also found in all of the cell walls of the root with the exception of lateral
      root-cap cell walls. It is striking that these three polysaccharide epitopes are
      not uniformly distributed (or accessible) within the walls of a given cell, nor
      are these epitopes distributed equally across the two walls laid down by adjacent
      cells. Our results further suggest that the biosynthesis and differentiation of
      primary cell walls in plants are precisely regulated in a temporal, spatial, and
      developmental manner.

PMID- 12226271
TI  - Appearance of Novel Glucose-6-Phosphate Dehydrogenase Isoforms in Chlamydomonas
      reinhardtii during Growth on Nitrate.
AB  - Extractable glucose-6-phosphate dehydrogenase activity is higher from N-limited
      Chlamydomonas reinhardtii cells than from N-sufficient cells. Native gels reveal
      that the isoform complexity varies depending on the form of N supplied. The
      isoforms associated with NO3- growth appear within 2 h of switching cells from
      NH4+ to NO3-.

PMID- 12226272
TI  - Regulation of Chlorophyll Biosynthesis in Angiosperms.

PMID- 12226273
TI  - Little or No Repair of Cyclobutyl Pyrimidine Dimers Is Observed in the Organellar
      Genomes of the Young Arabidopsis Seedling.
AB  - A Southern-blot-based, site-specific assay for ultraviolet (UV)-induced
      cyclobutyl pyrimidine dimers (CPDs), employing the CPD-specific enzyme T4
      endonuclease V, was used to follow the repair of this lesion in particular DNA
      sequences in 5- to 6-d-old Arabidopsis thaliana seedlings. CPDs, measured as
      enzyme-sensitive sites, in nuclear sequences were removed rapidly in the light
      but were repaired slowly, if at all, in the dark. This result was identical to
      that obtained in prior analyses of CPDs in total cellular DNA. Assay of
      representative chloroplast and mitochondrial sequences in the same DNA
      preparations revealed that, in contrast to nuclear sequences, enzyme-sensitive
      sites are inefficiently eliminated in both the presence and absence of visible
      light. These observations suggest that Arabidopsis seedlings possess little or no
      capacity for the repair of CPDs in the organellar genomes. Given the fact that
      the UV dose employed only marginally affected the growth of the seedlings, we
      suggest that Arabidopsis seedlings must possess very efficient mechanism(s) for
      the tolerance of UV-induced DNA damage.

PMID- 12226274
TI  - Highly Branched Phenotype of the Petunia dad1-1 Mutant Is Reversed by Grafting.
AB  - The recessive dad1-1 allele conditions a highly branched growth habit resulting
      from a proliferation of first- and second-order branches. Unlike the wild-type
      parent, which has lateral branching delayed until the third or fourth leaf node
      distal to the cotyledons, dad1-1 initiates lateral branching from each cotyledon
      axil. In addition to initiating lateral branching sooner than the wild type, dad1
      1 sustains branching through more nodes on the main shoot axis than the wild
      type. In keeping with a propensity for branching at basal nodes, dad1-1 produces
      second-order branches at the proximal-most nodes on first-order branches and
      small shoots from accessory buds at basal nodes on the main shoot axis.
      Additional traits associated with the mutation are late flowering, adventitious
      root formation, shortened internodes, and mild leaf chlorosis. Graft studies show
      that a dad1-1 scion, when grafted onto wild-type stock, is converted to a
      phenotype resembling the wild type. Furthermore, a small wild-type interstock
      fragment inserted between a mutant root stock and a mutant scion is sufficient to
      convert the dad1-1 scion from mutant to a near wild-type appearance. The
      recessive dad1-1 phenotype combines traits associated with cytokinin
      overexpression, auxin overexpression, and gibberellin limitation, which suggests
      a complex interaction of hormones in establishing the mutant phenotype.

PMID- 12226275
TI  - The Refined Three-Dimensional Structure of Pectate Lyase E from Erwinia
      chrysanthemi at 2.2 A Resolution.
AB  - The crystal structure of pectate lyase E (PelE; EC 4.2.2.2) from the
      enterobacteria Erwinia chrysanthemi has been refined by molecular dynamics
      techniques to a resolution of 2.2 A and an R factor (an agreement factor between
      observed structure factor amplitudes) of 16.1%. The final model consists of all
      355 amino acids and 157 water molecules. The root-mean-square deviation from
      ideality is 0.009 A for bond lengths and 1.721[deg] for bond angles. The
      structure of PelE bound to a lanthanum ion, which inhibits the enzymatic
      activity, has also been refined and compared to the metal-free protein. In
      addition, the structures of pectate lyase C (PelC) in the presence and absence of
      a lutetium ion have been refined further using an improved algorithm for
      identifying waters and other solvent molecules. The two putative active site
      regions of PelE have been compared to those in the refined structure of PelC. The
      analysis of the atomic details of PelE and PelC in the presence and absence of
      lanthanide ions provides insight into the enzymatic mechanism of pectate lyases.

PMID- 12226276
TI  - Direct Measurement of 59Fe-Labeled Fe2+ Influx in Roots of Pea Using a Chelator
      Buffer System to Control Free Fe2+ in Solution.
AB  - Fe2+ transport in plants has been difficult to quantify because of the inability
      to control Fe2+ activity in aerated solutions and non-specific binding of Fe to
      cell walls. In this study, a Fe(II)-3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine
      4[prime]4"-disulfonic acid buffer system was used to control free Fe2+ in uptake
      solutions. Additionally, desorption methodologies were developed to adequately
      remove nonspecifically bound Fe from the root apoplasm. This enabled us to
      quantify unidirectional Fe2+ influx via radiotracer (59Fe) uptake in roots of pea
      (Pisum sativum cv Sparkle) and its single gene mutant brz, an Fe
      hyperaccumulator. Fe influx into roots was dramatically inhibited by low
      temperature, indicating that the measured Fe accumulation in these roots was due
      to true influx across the plasma membrane rather than nonspecific binding to the
      root apoplasm. Both Fe2+ influx and Fe translocation to the shoots were
      stimulated by Fe deficiency in Sparkle. Additionally, brz, a mutant that
      constitutively exhibits high ferric reductase activity, exhibited higher Fe2+
      influx rates than +Fe-grown Sparkle. These results suggest that either Fe
      deficiency triggers the induction of the Fe2+ transporter or that the enhanced
      ferric reductase activity somehow stimulates the activity of the existing Fe2+
      transport protein.

PMID- 12226277
TI  - Intracellular Localization of Phospholipase D in Leaves and Seedling Tissues of
      Castor Bean.
AB  - The intracellular distribution of phospholipase D (PLD; EC 3.1.4.4) in castor
      bean (Ricinus communis L.) tissues was investigated by subcellular fractionation
      and by immuno-electron microscopy. Centrifugal fractionation revealed that most
      PLD in young leaves was soluble, whereas in mature leaves a majority of PLD was
      associated with microsomal membranes. Further separation of microsomal membranes
      by a two-phase partitioning system indicated that PLD was associated with both
      plasma and intracellular membranes. Sucrose gradient separation of intracellular
      membranes showed PLD present in the endoplasmic reticulum, a submicrosomal band,
      and in soluble fractions but not in mitochondria and glyoxysomes of
      postgermination endosperm. Immunocytochemical studies found high gold labeling in
      vacuoles in young leaves, suggesting that the high level of soluble PLD in young
      leaves is due to release of PLD from vacuoles during tissue disruption. In
      addition to the labeling in vacuoles, gold particles were also found in the
      cytoplasmic matrices and plasma membrane in leaves and in 2-d postgermination
      seedlings. Collectively, these results show that PLD in castor bean leaf and
      seedling tissues is localized in the vacuole and is associated with the
      endoplasmic reticulum and plasma membrane and that the relative distribution
      between the soluble and membrane compartments changes during castor bean leaf
      development.

PMID- 12226278
TI  - Water Deficit-Induced Changes in Concentrations in Proline and Some Other Amino
      Acids in the Phloem Sap of Alfalfa.
AB  - Changes in amino acid composition of alfalfa (Medicago sativa L.) phloem sap were
      studies in response to a water deficit. Sap was collected by stylectomy. As the
      leaf water potential ([psi]) decreased from -0.4 to -2.0 MPa, there was
      significant increase of the total amino acid concentration, due to that of some
      amino acids: proline, valine, isoleucine, leucine, glutamic acid, aspartic acid,
      and threonine. Asparagine concentration, which is the main amino acid assayed in
      the phloem sap of alfalfa (it accounts for 70% of the total content), did not
      vary with the plant water status. The other amino acid concentrations remained
      stable as [psi] varied; in particular, [gamma]-amino butyric acid concentration
      remained unchanged, whereas it varied in response to wounding. The more striking
      change in the sieve tubes was the accumulation of proline, which was observed
      below a [psi] threshold value of about -0.9 MPa (concentration x60 for a decrease
      of [psi] from -0.9 to -2.0 MPa). The role of such changes in phloem sap amino
      acid concentration in osmotic adjustment of growing tissues is discussed.

PMID- 12226279
TI  - Photosystem II Excitation Pressure and Photosynthetic Carbon Metabolism in
      Chlorella vulgaris.
AB  - Chlorella vulgaris grown at 5[deg]C/150 [mu]mol m-2 s-1 mimics cells grown under
      high irradiance (27[deg]C/2200 [mu]mol m-2 s-1). This has been rationalized
      through the suggestion that both populations of cells were exposed to comparable
      photosystem II (PSII) excitation pressures measured as the chlorophyll a
      fluorescence quenching parameter, 1 - qP (D.P. Maxwell, S. Falk, N.P.A. Huner
      [1995] Plant Physiol 107: 687-694). To assess the possible role(s) of feed-back
      mechanisms on PSII excitation pressure, stromal and cytosolic carbon metabolism
      were examined. Sucrose phosphate synthase and fructose-1,6-bisphosphatase
      activities as well as the ratios of fructose-1,6-bisphosphate/fructose-6
      phosphate and sucrose/starch indicated that cells grown at 27[deg]C/2200 [mu]mol
      m-2 s-1 appeared to exhibit a restriction in starch metabolism. In contrast,
      cells grown at 5[deg]C/150 [mu]mol m-2 s-1 appeared to exhibit a restriction in
      the sucrose metabolism based on decreased cytosolic fructose-1,6- bisphosphatase
      and sucrose phosphate synthase activities as well as a low sucrose/starch ratio.
      These metabolic restrictions may feed-back on photosynthetic electron transport
      and, thus, contribute to the observed PSII excitation pressure. We conclude that,
      although PSII excitation pressure may reflect redox regulation of photosynthetic
      acclimation to light and temperature in C. vulgaris, it cannot be considered the
      primary redox signal. Alternative metabolic sensing/signaling mechanisms are
      discussed.

PMID- 12226280
TI  - Induction of Male Sterility in Wheat by Meiotic-Stage Water Deficit Is Preceded
      by a Decline in Invertase Activity and Changes in Carbohydrate Metabolism in
      Anthers.
AB  - Water deficit during meiosis in pollen mother cells of wheat (Triticum aestivum
      L.) induces male sterility, which can reduce grain set by 40 to 50%. In plants
      stressed during meiosis and then rewatered, division of pollen mother cells
      proceeds normally but subsequent pollen development is arrested 3 or 4 d later.
      An inhibition of starch accumulation within the pollen grain suggested that an
      alteration in carbohydrate metabolism or assimilate supply may be involved in
      pollen abortion. We measured levels of various carbohydrates and activities of
      key enzymes of Suc metabolism and starch synthesis at different stages of pollen
      development in anthers collected from well-watered and water-stressed plants.
      Compared to controls, soluble sugars increased in anthers stressed during
      meiosis, then decreased at later poststress stages. Sucrose and myoinositol
      accounted for part of the sugar accumulation. The activity of soluble acid
      invertase declined 4-fold during the stress period and never recovered
      thereafter. Sucrose synthase activity during starch accumulation in pollen was
      also lower in the anthers of plants stressed at meiosis. Stress had little
      negative effect on the activities of ADP-glucose pyrophosphorylase or soluble and
      granule-bound starch synthase during starch accumulation in pollen, although at
      the earlier stages, ADP-glucose pyrophosphorylase activity in stressed anthers
      was slightly lower compared to controls. The results suggest that carbohydrate
      starvation per se and inhibition of the enzymes of starch synthesis probably were
      not responsible for the stress-induced pollen abortion. Instead, an inability to
      metabolize incoming sucrose to hexoses may be involved in this developmental
      lesion.

PMID- 12226281
TI  - Demand-Driven Control of Root ATP Sulfurylase Activity and SO42- Uptake in Intact
      Canola (The Role of Phloem-Translocated Glutathione).
AB  - The activity of ATP sulfurylase extracted from roots of intact canola (Brassica
      napus L. cv Drakkar) increased after withdrawal of the S source from the nutrient
      solution and declined after refeeding SO42- to S-starved plants. The rate of SO42
      uptake by the roots was similarly influenced. Identical responses were obtained
      in SO42- -fed roots when one-half of the root system was starved for S. The
      internal levels of SO42- and glutathione (GSH) declined after S starvation of the
      whole root system, but only GSH concentration declined in +S roots of plants from
      split root experiments. The concentration of GSH in phloem exudates decreased
      upon transfer of plants to S-free solution. Supplying GSH or cysteine to roots,
      either exogenously or internally via phloem sap, inhibited both ATP sulfurylase
      activity and SO42- uptake. Buthionine sulfoximine, an inhibitor of GSH synthesis,
      reversed the inhibitory effect of cysteine on ATP sulfurylase. It is hypothesized
      that GSH is responsible for mediating the responses to S availability. ATP
      sulfurylase activity and the SO42- uptake rate are regulated by similar demand
      driven processes that involve the translocation of a phloem-transported message
      (possibly GSH) to the roots that provides information concerning the nutritional
      status of the leaves.

PMID- 12226282
TI  - The Effect of Leaf Temperature and Photorespiratory Conditions on Export of
      Sugars during Steady-State Photosynthesis in Salvia splendens.
AB  - Export and photosynthesis in leaves of Salvia splendens were measured
      concurrently during steady-state 14CO2 labeling conditions. Under ambient CO2 and
      O2 conditions, photosynthesis and export rates were similar at 15 and 25[deg]C,
      but both declined as leaf temperature was raised from 25 to 40[deg]C. Suppressing
      photorespiration between 15 and 40[deg]C by manipulating CO2 and O2 levels
      resulted in higher rates of leaf photosynthesis, total sugar synthesis, and
      export. There was a linear relationship between the rate of photosynthesis and
      the rate of export between 15 and 35[deg]C. At these temperatures, 60 to 80% of
      the carbon fixed was readily exported with sucrose, raffinose, and stachyose,
      which together constituted over 90% of phloem mobile assimilates. Above 35[deg]C,
      however, export during photosynthesis was inhibited both in photorespiratory
      conditions, which inhibited photosynthesis, and in nonphotorespiratory
      conditions, which did not inhibit photosynthesis. Sucrose and raffinose but not
      stachyose accumulated in the leaf at 40[deg]C. When leaves were preincubated at
      40[deg]C and then cooled to 35[deg]C, export recovered more slowly than
      photosynthesis. These data are consistent with the view that impairment of export
      processes, rather than photosynthetic processes associated with light trapping,
      carbon reduction, and sucrose synthesis, accounted for the marked reduction in
      export between 35 and 40[deg]C. Taken together, the data indicated that
      temperature changes between 15 and 40[deg]C had two effects on photosynthesis and
      concurrent export. At all temperatures, suppressing photorespiration increased
      both photosynthesis and export, but above 35[deg]C, export processes were more
      directly inhibited independent of changes in photorespiration and photosynthesis.

PMID- 12226283
TI  - Dynamics of Changing Intercellular CO2 Concentration (ci) during Drought and
      Determination of Minimum Functional ci.
AB  - Nine conifer species with narrow (<5 mm), single-veined leaves were selected for
      the purpose of examining changes in intercellular CO2 concentration (ci) during
      drought. Due to the leaf morphology of the study plants, the confounding effects
      of nonhomogenous photosynthesis common to most reticulate-veined angiosperms were
      largely avoided, giving a clear picture of ci dynamics under increasing drought.
      A characteristic biphasic response was observed in all species, with an initial
      stomatal control phase resulting in a substantial reduction in ci as stomatal
      conductance (gs) decreased. As gs reached low levels, a strong nonstomatal
      limitation phase was observed, causing ci to increase as gs approached a minimum.
      This nonstomatal phase was linked to a concomitant rapid decrease in the
      fluorescence parameter quantum efficiency, indicating the onset of nonreversible
      photoinhibition. The ratio of internal to atmospheric CO2 concentration (ci/ca)
      decreased from values of between 0.68 and 0.57 in undroughted plants to a
      minimum, (ci/ca)min, which was well defined in each species, ranging from 0.10 in
      Actinostrobus acuminatus to 0.36 in Acmopyle pancheri. A high correlation was
      found to exist between (ci/ca)min and leaf water potential measured at
      (ci/ca)min. Species developing high maximum intrinsic water use efficiencies (low
      [ci/ca]min), such as A. acuminatus, did so at lower leaf water potentials (-4.5
      MPa) than more mesic species (-1.75 MPa for A. pancheri). It is concluded that in
      the absence of patchy stomatal closure, (ci/ca)min gives a good representation of
      the drought tolerance of foliage.

PMID- 12226284
TI  - Glycolytic Flux and Hexokinase Activities in Anoxic Maize Root Tips Acclimated by
      Hypoxic Pretreatment.
AB  - Several enzyme activities were measured in extracts from acclimated and
      nonacclimated maize (Zea mays) root tips at pH 6.5 and 7.5, corresponding to
      cytoplasmic pH in anaerobiosis or aerobiosis, respectively, to determine what
      causes the decline of the glycolytic flux observed in anoxia in nonacclimated
      tips. We found that phosphorylation of hexoses by kinases was a major limiting
      step of glycolysis in anoxia. When fructose was substituted for glucose,
      glycolysis was slightly enhanced and survival improved, but neither matched that
      of acclimated tips. Decrease of kinase activities was not the result of
      proteolytic degradation but was more likely the result of inhibition by internal
      factors (low pH and low ATP). There was no evidence of induction during the
      hypoxic pretreatment of isoenzymes better adapted to the anoxic cellular
      environment. Maintenance of the glycolytic flux in acclimated tissues is
      explained by a combination of a rise in kinase activities and decreased
      inhibition resulting from a higher cytoplasmic pH and ATP content. The behavior
      of intact root tips is discussed in comparison with the behavior of excised root
      tips.

PMID- 12226285
TI  - The Role of Magnesium, Pyrophosphate, and Their Complexes as Substrates and
      Activators of the Vacuolar H+-Pumping Inorganic Pyrophosphatase (Studies Using
      Ligand Protection from Covalent Inhibitors).
AB  - Inhibitors preferentially and covalently reactive with cysteine, arginine,
      histidine, and carboxyl-containing residues were inhibitory to the plant vacuolar
      H+-transporting inorganic pyrophosphatase (H+-PPase) from Vigna radiata (mung
      bean) and Beta vulgaris (red beet), but hydrophobic compounds and those reactive
      with tyrosine and lysine were less effective. Inhibition by 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide, phenylglyoxal, and N-ethylmaleimide was
      decreased in the presence of Mg2+ or mixtures of Mg2+ and inorganic pyrophosphate
      (PPi) but not by PPi alone. None of these ligands affected inhibition by reagents
      reactive with histidine. The Mg2+ dependence of protection from 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide inhibition followed first-order kinetics and
      yielded a Km for free Mg2+ of 20 to 23 [mu]M. Protection from inhibition by N
      ethylmaleimide and phenylglyoxal varied as a function of Mg2PPi concentration,
      suggesting that this is the substrate for the H+-PPase. Protection by Mg2PPi
      followed Michaelis-Menten kinetics with a Km of approximately 2 [mu]M. These
      results are consistent with the predictions of a kinetic model for the H+-PPase
      (R.A. Leigh, A.J. Pope, I.R. Jennings, D. Sanders [1992] Plant Physiol 100: 1698
      1750), which identified free Mg2+ as an allosteric activator (Km = 25 [mu]M) and
      Mg2PPi as the substrate (Km = 2.5-5 [mu]M).

PMID- 12226286
TI  - Differential Localization of Carbohydrate Epitopes in Plant Cell Walls in the
      Presence and Absence of Arbuscular Mycorrhizal Fungi.
AB  - Two monoclonal antibodies (McAbs) generated against rhamnogalacturonan I and
      characterized as specific for a terminal [alpha]-(1->2)-linked fucosyl-containing
      epitope (CCRC-M1) and for an arabinosylated [beta]-(1,6)-galactan epitope (CCRC
      M7) were used in immunogold experiments to determine the distribution of the
      epitopes in four plants. Allium porrum, Zea mays, Trifolium repens, and Nicotiana
      tabacum plants were chosen as representatives of monocots and dicots with
      different wall structures. Analyses were performed on root tissues in the
      presence and absence of arbuscular mycorrhizal fungi. A differential localization
      of the two cell wall epitopes was found between tissues and between species: for
      example, in leek, CCRC-M1 labeled epidermal and hypodermal cells, whereas CCRC-M7
      labeled cortical cells only. Clover walls were labeled by both McAbs, whereas
      maize and tobacco were only labeled by CCRC-M7. In the presence of the arbuscular
      mycorrhizal fungi, labeling was additionally found in an apoplastic compartment
      typical of the symbiosis (the interface) occurring around the intracellular
      hyphae. Epitopes binding both McAbs were found in the interfacial material, and
      their distribution mirrored the pattern found in the host cell wall. These
      findings demonstrate that the composition of the interface zone in a fungus-plant
      symbiosis reflects the composition of the wall of the host cell.

PMID- 12226287
TI  - Purification and Characterization of a Cryoprotective Protein (Cryoprotectin)
      from the Leaves of Cold-Acclimated Cabbage.
AB  - We have purified a protein (cryoprotectin) from the leaves of cold-acclimated
      cabbage (Brassica oleracea L.) that protects thylakoids from nonacclimated
      spinach (Spinacia oleracea L.) against freeze-thaw damage. The procedure involves
      precipitations by heat, ammonium sulfate, and the glycosaminoglycan heparin and
      column chromatography on Polyamide 6 and a C18 reverse-phase matrix. After
      reverse-phase chromatography we obtained a single band of an apparent molecular
      mass of 7 kD when fractions that showed cryoprotective activity were analyzed by
      sodium dodecyl sulfate gel electrophoresis and silver staining. Gel-filtration
      experiments confirmed that the active protein is a monomer of 7 kD native
      molecular mass. This 7-kD protein could be purified only from cold-acclimated
      cabbage, but not from plants grown under nonacclimating conditions. Using
      peroxidase-labeled lectins, we show that cryoprotectin is a glycoprotein and that
      the saccharide moiety contains [alpha]1-3-linked fucose.

PMID- 12226288
TI  - Regulation of H+ Extrusion and Cytoplasmic pH in Maize Root Tips Acclimated to a
      Low-Oxygen Environment.
AB  - We tested the hypothesis that H+ extrusion contributes to cytoplasmic pH
      regulation and tolerance of anoxia in maize (Zea mays) root tips. We studied root
      tips of whole seedlings that were acclimated to a low-oxygen environment by
      pretreatment in 3% (v/v) O2. Acclimated root tips characteristically regulate
      cytoplasmic pH near neutrality and survive prolonged anoxia, whereas
      nonacclimated tips undergo severe cytoplasmic acidosis and die much more quickly.
      We show that the plasma membrane H+-ATPase can operate under anoxia and that net
      H+ extrusion increases when cytoplasmic pH falls. However, at an external pH near
      6.0, H+ extrusion contributes little to cytoplasmic pH regulation. At more acidic
      external pH values, net H+ flux into root tips increases dramatically, leading to
      a decrease in cytoplasmic pH and reduced tolerance of anoxia. We present evidence
      that, under these conditions, H+ pumps are activated to partly offset acidosis
      due to H+ influx and, thereby, contribute to cytoplasmic pH regulation and
      tolerance of anoxia. The regulation of H+ extrusion under anoxia is discussed
      with respect to the acclimation response and mechanisms of intracellular pH
      regulation in aerobic plant cells.

PMID- 12226289
TI  - Calorimetric Properties of Dehydrating Pollen (Analysis of a Desiccation-Tolerant
      and an Intolerant Species).
AB  - The physical state of water in the desiccation-tolerant pollen of Typha latifolia
      L. and the desiccation-sensitive pollen of Zea mays L. was studied using
      differential scanning calorimetry in an attempt to further unravel the complex
      mechanisms of desiccation tolerance. Melting transitions of water were not
      observed at water content (wc) values less than 0.21 (T. latifolia) and 0.26 (Z.
      mays) g H2O/g dry weight. At moisture levels at which melting transitions were
      not observable, water properties could be characterized by changes in heat
      capacity. Three hydration regions could be distinguished with the defining wc
      values changing as a function of temperature. Shifts in baseline power resembling
      second-order transitions were observed in both species and were interpreted as
      glass-to-liquid transitions, the glass-transition temperatures being dependent on
      wc. Irrespective of the extent of desiccation tolerance, both pollens exhibited
      similar state diagrams. The viability of maize pollen at room temperature
      decreased gradually with the removal of the unfrozen water fraction. In maize,
      viability was completely lost before grains were sufficiently dried to enter into
      a glassy state. Apparently, the glassy state per se cannot provide desiccation
      tolerance. From the existing data, we conclude that, although no major
      differences in the physical behavior of water could be distinguished between
      desiccation-tolerant and -intolerant pollens, the physiological response to the
      loss of water varies between the two pollen types.

PMID- 12226290
TI  - Attenuation of the Phenotype Caused by the Root-Inducing, Left-Hand, Transferred
      DNA and Its rolA Gene (Correlations with Changes in Polyamine Metabolism and DNA
      Methylation).
AB  - We present four examples of attenuation of the transformed phenotype caused by
      the root-inducing, left-hand, transferred DNA from Agrobacterium rhizogenes in
      tobacco (Nicotiana tabacum). The first was associated with a genetic variable
      (homozygosity for the T-DNA), and the second was induced at the physiological
      level by putrescine and tyramine, suggesting that the transformed phenotype
      depends on defective polyamine metabolism. Physiological attenuation is further
      illustrated in the third example, in which the inhibition of flowering caused by
      P35S-rolA, a gene from the root-inducing, left-hand, transferred DNA driven by a
      strong viral promoter, was attenuated by grafting the transformed shoot onto non
      transformed rootstock that had been induced to flower. Infertility in the
      resulting flowers was corrected by a mixture of putrescine and tyramine,
      indicating that P35S-rolA inhibited flowering through interference with polyamine
      conjugation and that tyramine was essential to fertility. A fourth example of
      attenuation of the transformed phenotype occurred in lateral branches of plants
      expressing rolA under the control of its native promoter. In these branches,
      reduction in the accumulation of rolA transcripts was correlated with the
      methylation of a site 3[prime] to the rolA coding sequence; thus, the transformed
      plant seems capable of recognizing and repressing a gene that interferes with
      flowering.

PMID- 12226291
TI  - Sucrolytic Enzyme Activities in Cotyledons of the Faba Bean (Developmental
      Changes and Purification of Alkaline Invertase).
AB  - In terms of maximum extractable catalytic activity, sucrose synthase is the
      predominant sucrolytic enzyme in developing cotyledons of faba bean (Vicia faba
      L.). Although acid invertase activity is extremely low, there is significant
      activity of alkaline invertase, the majority of which is extractable only with
      high concentrations of NaCl. Calculations of potential activity in vivo indicate
      that alkaline invertase is the predominant sucrolytic enzyme from 50 days after
      anthesis onward. However, at almost all stages of cotyledon development analyzed,
      the maximum extractable catalytic activities of both enzymes is in excess of the
      actual rate of starch deposition. Two forms of alkaline invertase were identified
      in developing cotyledons. The major form has been purified to homogeneity, and
      antibodies have been raised against it. The native protein has a molecular mass
      of about 238 [plus or minus] 4.5 kD. It is apparently a homotetramer (subunit
      molecular mass 53.4 [plus or minus] 0.9 kD). The enzyme has a pH optimum of 7.4,
      an isoelectric point of 5.2, and a Km[sucrose] of 10 mM and is inhibited by Tris
      (50% inhibition at 5 mM) and fructose (30% inhibition at 10 mM). Bean alkaline
      invertase is a [beta]-fructofuranosidase with no significant activity against
      raffinose, stachyose, trehalose, maltose, or lactose.

PMID- 12226292
TI  - Old Enzymes for a New Job (Herbicide Detoxification in Plants).

PMID- 12226293
TI  - Nitrate Reductase Biochemistry Comes of Age.

PMID- 12226294
TI  - Modulation of Calmodulin mRNA and Protein Levels in Barley Aleurone.
AB  - Changes in calmodulin (CaM) mRNA and protein were investigated in aleurone layers
      of barley (Hordeum vulgare L. cv Himalaya) incubated in the presence and absence
      of calcium, gibberellic acid (GA3), and abscisic acid (ABA). CaM mRNA levels
      increased rapidly and transiently following incubation of aleurone layers in H2O,
      CaCl2, or GA3. The increase in CaM mRNA was prevented by ABA. This increase in
      CaM mRNA was brought about by physical stimulation during removal of the starchy
      endosperm from the aleurone layer. CaM protein levels did not increase in
      response to physical stimulation. Only incubation in GA3 plus CaCl2 brought about
      a rapid increase in CaM protein levels in the aleurone cell. ABA reduced the
      level of CaM protein below that found at the beginning of the incubation period.
      The rise in CaM protein preceded increases in the synthesis and secretion of
      [alpha]-amylase. Immunocytochemistry with monoclonal antibodies to carrot and
      mung bean CaM was used to localize CaM in aleurone protoplasts. Monoclonal
      antibodies to tubulin and polyclonal antibodies to tonoplast intrinsic protein
      and malate synthase were used as controls. CaM was localized to the nucleus, the
      vacuolar membrane, and the cytosol, but was not associated with microtubules.

PMID- 12226295
TI  - Characterization of Membrane Properties in Desiccation-Tolerant and -Intolerant
      Carrot Somatic Embryos.
AB  - In previous studies, we have shown that carrot (Daucus carota L.) somatic embryos
      acquire complete desiccation tolerance when they are treated with abscisic acid
      during culture and subsequently dried slowly. With this manipulable system at
      hand, we have assessed damage associated with desiccation intolerance. Fast
      drying caused loss of viability, and all K+ and carbohydrates leached from the
      somatic embryos within 5 min of imbibition. The phospholipid content decreased by
      about 20%, and the free fatty acid content increased, which was not observed
      after slow drying. However, the extent of acyl chain unsaturation was unaltered,
      irrespective of the drying rate. These results indicate that, during rapid
      drying, irreversible changes occur in the membranes that are associated with
      extensive leakage and loss of germinability. The status of membranes after 2 h of
      imbibition was analyzed in a freeze-fracture study and by Fourier transform
      infrared spectroscopy. Rapidly dried somatic embryos had clusters of
      intramembraneous particles in their plasma membranes, and the transition
      temperature of isolated membranes was above room temperature. Membrane proteins
      were irreversibly aggregated in an extended [beta]-sheet conformation and had a
      reduced proportion of [alpha]-helical structures. In contrast, the slowly dried
      somatic embryos had irregularly distributed, but non-clustered, intramembraneous
      particles, the transition temperature was below room temperature, and the
      membrane proteins were not aggregated in a [beta]-sheet conformation. We suggest
      that desiccation sensitivity of rapidly dried carrot somatic embryos is
      indirectly caused by an irreversible phase separation in the membranes due to de
      esterification of phospholipids and accumulation of free fatty acids.

PMID- 12226296
TI  - Drought-Induced Xylem Dysfunction in Petioles, Branches, and Roots of Populus
      balsamifera L. and Alnus glutinosa (L.) Gaertn.
AB  - Variation in vulnerability to xylem cavitation was measured within individual
      organs of Populus balsamifera L. and Alnus glutinosa (L.) Gaertn. Cavitation was
      quantified by three different techniques: (a) measuring acoustic emissions, (b)
      measuring loss of hydraulic conductance while air-dehydrating a branch, and (c)
      measuring loss of hydraulic conductance as a function of positive air pressure
      injected into the xylem. All of these techniques gave similar results. In
      Populus, petioles were more resistant than branches, and branches were more
      resistant than roots. This corresponded to the pattern of vessel width: maximum
      vessel diameter in 1- to 2-year-old roots was 140 [mu]m, compared to 65 and 45
      [mu]m in rapidly growing 1-year-old shoots and petioles, respectively. Cavitation
      in Populus petioles started at a threshold water potential of -1.1 MPa. The
      lowest leaf water potential observed was -0.9 MPa. In Alnus, there was no
      relationship between vessel diameter and the cavitation response of a plant
      organ. Although conduits were narrower in petioles than in branches, petioles
      were more vulnerable to cavitation. Cavitation in petioles was detected when
      water potential fell below -1.2 MPa. This value equaled midday leaf water
      potential in late June. As in Populus, roots were the most vulnerable organ. The
      significance of different cavitation thresholds in individual plant organs is
      discussed.

PMID- 12226297
TI  - Chloroplast Distribution in Arabidopsis thaliana (L.) Depends on Light Conditions
      during Growth.
AB  - Chloroplasts of Arabidopsis thaliana move in response to blue light. Sensitivity
      to light and the range of fluence rates to which the chloroplasts respond were
      found to be comparable to those of other higher plants studied. We investigated
      typical chloroplast distributions in Arabidopsis grown under three different
      light conditions:standard-light conditions, similar to natural light intensities;
      weak-light intensities, close to the compensation point of photosynthesis; and
      strong-light intensities, close to the saturation of the light-response curve of
      photosynthesis. We observed a striking difference in chloroplast arrangement in
      darkness between plants grown under weak- and strong-light conditions. There was
      a slight difference after weak-light pretreatment, and the arrangements of
      chloroplasts after strong-light pretreatment in both plant groups were very
      similar. These results support the ecological significance of chloroplast
      movements.

PMID- 12226298
TI  - The N-1-Naphthylphthalamic Acid-Binding Protein Is an Integral Membrane Protein.
AB  - N-1-Naphthylphthalmic acid (NPA)-binding protein is a plasmalemma (PM) protein
      involved in the control of cellular auxin efflux. We re-evaluated the spatial
      relationship of this protein with the PM of zucchini (Cucurbita pepo L.)
      hypocotyls. First, Triton X-114 partitioning indicated that the NPA-binding
      protein was more hydrophobic than most PM proteins. Second, the NPA-binding
      activity was found to be resistant to proteolytic digestion in membranes. Maximum
      concentrations of binding sites for NPA were virtually identical in untreated and
      proteinase K-treated PMs: 19.2 and 20.6 pmol [3H]NPA bound/mg protein,
      respectively. The insensitivity of the NPA-binding protein was not due to its
      presence inside tightly sealed vesicles or due to lack of protease activity in
      the conditions tested. This protein could be made sensitive to proteolytic
      degradation upon solubilization by 3-[(3-cholamidopropyl)dimethylammonio]-1
      propanesulfonate in the presence of sodium molybdate. Proteinase K treatment
      decreased the concentration of binding sites to 0.84 pmol [3H]NPA bound/mg
      protein from 9.2 for untreated, solubilized PM. Third, this activity could not be
      solubilized by chaotropic agents or sodium carbonate treatment of intact PM. This
      study indicates that the NPA-binding protein may be an integral membrane protein
      and contradicts previously reported findings that suggested that this protein was
      peripheral to the PM.

PMID- 12226299
TI  - Inhibition of Blue Light-Dependent H+ Pumping by Abscisic Acid in Vicia Guard
      Cell Protoplasts.
AB  - Blue-light (BL)-dependent H+ pumping in guard-cell protoplasts (GCPs) from Vicia
      faba was inhibited by 65% in the presence of abscisic acid (ABA). The inhibition
      increased with the time after application of ABA and was concentration dependent
      with a saturating concentration of 1 [mu]M at pH 6.2. The inhibition was nearly
      independent of the pH of the medium in the range 5.4 to 7.2 when ABA was applied
      at 10 [mu]M, whereas it was dependent on pH when the ABA concentration was
      decreased. The protonated form of ABA was saturating at 40 nM in inhibiting BL
      dependent H+ pumping under various experimental conditions, whereas the
      dissociated form at 500 nM had no inhibitory effect on the pumping, suggesting
      that the protonated form of ABA is the form active in inhibiting the pumping.
      Fusicoccin (10 [mu]M), an activator of plasma membrane H+-ATPase, induced H+
      pumping from GCPs, and the rate of H+ pumping was decreased to 70% by ABA. In
      contrast, ABA did not inhibit H+ pumping in isolated microsome vesicles from
      GCPs. These results suggest that the inhibition of BL-dependent H+ pumping by ABA
      in GCPs may be due to indirect inactivation of plasma membrane H+-ATPase and/or
      inhibition of the BL-signaling pathway. The pump inhibition by ABA causes
      membrane depolarization and can be an initial step to induce stomatal closure and
      reduces the transpirational water loss under drought stress in the daytime.

PMID- 12226300
TI  - Isolation of a Protein Containing Covalently Linked Large and Small Subunits of
      Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase from Botryococcus braunii.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and a 66-kD protein
      were co-purified from solubilized microsomal preparations of the green alga
      Botryococcus braunii by Green A agarose, sucrose density gradient, MonoQ, and gel
      filtration. The 66-kD protein remained intact after 6 M urea treatment and sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. It could be detected in the
      soluble fraction of the cell-free extract but appeared to be more abundant in the
      microsomal preparations. It cross-reacted with antibodies raised against Rubisco
      holoenzyme, large and small subunits, indicating that the 66-kD protein contains
      both the large and the small subunits of Rubisco. The N-terminal amino acid
      sequence of this protein and that of a proteolytic fragment showed high homology
      with the mature Rubisco small subunits, and the sequence of another proteolytic
      fragment showed high homology with that of the Rubisco large subunit. It is
      concluded that the 66-kD protein is produced by cross-linking of large and small
      sub-units of Rubisco in the cell.

PMID- 12226301
TI  - Alterations in Structural Polysaccharides during Liquefaction of Tomato Locule
      Tissue.
AB  - The locule tissue of tomato (Lycopersicon esculentum, Mill.) undergoes extensive
      liquefaction during ripening. In this study, the solubility, molecular mass, and
      glycosyl composition of locule pectic and alkali-soluble polysaccharides were
      examined with the aim of identifying features contributing to the unique
      properties of this tissue. Ethanol-insoluble solids were prepared from de-seeded
      locule tissue from tomato fruit at the immature green (IMG), mature green, and
      breaker stages of development. Ethanol-insoluble pectins were extracted
      sequentially in H2O, 50 mM trans-1,2-diaminocyclohexane-N,N,N[prime],N[prime]
      tetraacetic acid, 50 mM Na2CO3, and 4 M KOH. At the IMG stage, nearly 85% of the
      locule pectins were solubilized by water, trans-1,2-diaminocyclohexane
      N,N,N[prime],N[prime]-tetraacetic acid, and Na2CO3 solutions. Solubility
      increased only slightly with further locule development. The noncovalently
      associated polymers were of high molecular mass throughout liquefaction. Polymers
      extracted in mild alkali were of considerably lower molecular mass. Locule
      pectins in IMG fruit were heavily glycosylated with galactose, arabinose, and
      xylose. All pectin classes exhibited similar deglycosylation trends during
      liquefaction. Locule hemicelluloses were rich in glucose, xylose, and arabinose.
      These polymers collectively showed molecular mass downshifts with minimal
      compositional changes during liquefaction. The KOH-soluble material also included
      xylose-rich acidic polymers not matching the neutral sugar profile of the
      noncovalently associated pectic polymers.

PMID- 12226302
TI  - Mastoparan-Induced Intracellular Ca2+ Fluxes May Regulate Cell-to-Cell
      Communication in Plants.
AB  - The relationship of Ca2+ and plasmodesmatal closure was examined in staminal
      hairs of Setcreasea purpurea by microinjecting cells with active mastoparan (Mas
      7), inactive mastoparan (Mas-17), active inositol-1,4,5-trisphosphate (IP3), or
      inactive IP3. Calcium green dextran 10,000 was used to study cellular free Ca2+,
      and carboxyfluorescein was used to monitor plasmodesmatal closure. When Mas-7 was
      microinjected into the cytoplasm of cell 1 (the tip cell of a chain of cells), a
      rapid increase in calcium green dextran-10,000 fluorescence was observed in the
      cytoplasmic areas on both sides of the plasmodesmata connecting cells 1 and 2
      during the same time that the diffusion of carboxyfluorescein through them was
      blocked. The inhibition of cell-to-cell diffusion was transient, and the closed
      plasmodesmata reopened within 30 s. The elevated Ca2+ level near plasmodesmata
      was also transient and returned to base level in about 1.5 min. The transient
      increase in Ca2+, once initiated in cell 1, repeated with an oscillatory period
      of 3 min. Elevated Ca2+ and oscillations of Ca2+ were also observed near
      interconnecting cell walls throughout the chain of cells, indicating that the
      signal had been transmitted. Previously, we reported that IP3 closed
      plasmodesmata; now we report that it stimulated Ca2+ and oscillations similar to
      Mas-7. The effect was specific for similar concentrations of Mas-7 over Mas-17
      and active IP3 over inactive IP3. It is important that the Ca2+ channel blocker
      La3+ eliminated the responses from Mas-7 and IP3, indicating that an influx of
      Ca2+ was required. These results support the contention that plasmodesmata
      functioning is regulated via Ca2+ and that IP3 may be an intermediary between the
      stimulus and Ca2+ elevations.

PMID- 12226303
TI  - Solid-State 13C Nuclear Magnetic Resonance Characterization of Cellulose in the
      Cell Walls of Arabidopsis thaliana Leaves.
AB  - Solid-state 13C nuclear magnetic resonance was used to characterize the molecular
      ordering of cellulose in a cell-wall preparation containing mostly primary walls
      obtained from the leaves of Arabidopsis thaliana. Proton and 13C spin relaxation
      time constants showed that the cellulose was in a crystalline rather than a
      paracrystalline state or amorphous state. Cellulose chains were distributed
      between the interiors (40%) and surfaces (60%) of crystallites, which is
      consistent with crystallite cross-sectional dimensions of about 3 nm. Digital
      resolution enhancement revealed signals indicative of triclinic and monoclinic
      crystalline forms of cellulose mixed in similar proportions. Of the five nuclear
      spin relaxation processes used, proton rotating-frame relaxation provided the
      clearest distinction between cellulose and other cell-wall components for
      purposes of editing solid-state 13C nuclear magnetic resonance spectra.

PMID- 12226304
TI  - Volatile Semiochemicals Released from Undamaged Cotton Leaves (A Systemic
      Response of Living Plants to Caterpillar Damage).
AB  - Cotton plants (Gossypium hirsutum L.), attacked by herbivorous insects release
      volatile semiochemicals (chemical signals) that attract natural enemies of the
      herbivores to the damaged plants. We found chemical evidence that volatiles are
      released not only at the damaged site but from the entire cotton plant. The
      release of volatiles was detected from upper, undamaged leaves after 2 to 3 d of
      continuous larval damage on lower leaves of the same plant. Compounds released
      systemically were (Z)-3-hexenyl acetate, (E)-[beta]-ocimene, linalool, (E)-4,8
      dimethyl-1,3,7-nonatriene, (E)-[beta]-farnesene, (E,E)-[alpha]-farnesene, and
      (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene. All systemically released
      compounds are known to be induced by caterpillar damage and are not released in
      significant amounts by undamaged plants. Other compounds, specifically indole,
      isomeric hexenyl butyrates, and 2-methylbutyrates, known to be released by cotton
      in response to caterpillar damage, were not released systemically. However, when
      upper, undamaged leaves of a caterpillar-damaged plant were damaged with a razor
      blade, they released isomeric hexenyl butyrates, 2-methylbutyrates, and large
      amounts of constitutive compounds in addition to the previously detected induced
      compounds. Control plants, damaged with a razor blade in the same way, did not
      release isomeric hexenyl butyrates or 2-methylbutyrates and released
      significantly smaller amounts of constitutive compounds. Indole was not released
      systemically, even after artificial damage.

PMID- 12226305
TI  - Phosphoenolpyruvate Carboxylase Kinase in Tobacco Leaves Is Activated by Light in
      a Similar but Not Identical Way as in Maize.
AB  - We have previously reported the partial purification of a Ca2+- independent
      phosphoenolpyruvate carboxylase (PEPC) protein-serine/threonine kinase (PEPC-PK)
      from illuminated leaves of N-sufficient tobacco (Nicotiana tabacum L.) plants (Y.
      H. Wang, R. Chollet [1993] FEBS Lett 328: 215-218). We now report that this C3
      PEPC-kinase is reversibly light activated in vivo in a time-dependent manner. As
      the kinase becomes light activated, the activity and L-malate sensitivity of its
      target protein increases and decreases, respectively. The light activation of
      tobacco PEPC-PK is prevented by pretreatment of detached leaves with various
      photosynthesis and cytosolic protein-synthesis inhibitors. Similarly, specific
      inhibitors of glutamine synthetase block the light activation of tobacco leaf
      PEPC-kinase under both photorespiratory and nonphotorespiratory conditions. This
      striking effect is partially and specifically reversed by exogenous glutamine,
      whereas it has no apparent effect on the light activation of the maize (Zea mays
      L.) leaf kinase. Using an in situ "activity-gel" phosphorylation assay, we have
      identified two major Ca2+-independent PEPC-kinase catalytic polypeptides in
      illuminated tobacco leaves that have the same molecular masses (approximately 30
      and 37 kD) as found in illuminated maize leaves. Collectively, these results
      indicate that the phosphorylation of PEPC in N-sufficient leaves of tobacco (C3)
      and maize (C4) is regulated through similar but not identical light-signal
      transduction pathways.

PMID- 12226306
TI  - Heat-Shock Response in Heat-Tolerant and Nontolerant Variants of Agrostis
      palustris Huds.
AB  - The heat-shock response in heat-tolerant variants (SB) and non-tolerant variants
      (NSB) of creeping bentgrass (Agrostis palustris Huds.) was investigated. Both
      variants were derived from callus initiated from a single seed of the cultivar
      Penncross. SB and NSB synthesized heat-shock proteins (HSPs) of 97, 83, 70, 40,
      25, and 18 kD. There were no major differences between SB and NSB in the time or
      temperature required to induce the heat-shock response. When the HSPs synthesized
      by SB and NSB were analyzed by two-dimensional gel electrophoresis, it was
      apparent that SB synthesized two to three additional members of the HSP27 family,
      which were smaller (25 kD) and more basic than those synthesized by NSB. Analysis
      of F1 progeny of NSB x SB indicated that 7 of the 20 progeny did not synthesize
      the additional HSP25 polypeptides. These progeny were significantly less heat
      tolerant than progeny that did synthesize the additional HSP25 polypeptides. The
      X2 test of independence (X2 = 22.45, P < 0.001) indicated that heat tolerance and
      the presence of the additional HSP25 polypeptides are linked traits.

PMID- 12226307
TI  - Two Methyl Jasmonate-Insensitive Mutants Show Altered Expression of AtVsp in
      Response to Methyl Jasmonate and Wounding.
AB  - Jasmonates are plant signal molecules that are derived from lipids through the
      action of lipoxygenase. Jasmonates regulate gene expression during plant
      development and in response to water deficit, wounding, and pathogen elicitors.
      The signal transduction chain that mediates jasmonate action was investigated by
      isolating and studying two methyl jasmonate (MeJA)-insensitive mutants of
      Arabidopsis thaliana. The recessive mutants, jin1 and jin4, are nonallelic and
      neither corresponds to coi1, a previously identified MeJA-insensitive mutant.
      Both mutants showed reduced sensitivity to MeJA-mediated root growth inhibition
      as well as reduced MeJA induction of AtVsp in leaves. Expression of AtVsp in
      flowers was not altered in the mutants. Furthermore, MeJA modulation of the
      jasmonate-responsive lipoxygenase and phenylalanine ammonia lyase genes was not
      altered in the mutants. jin4 plants exhibited increased sensitivity to abscisic
      acid in seed germination assays, whereas jin1 plants showed wild-type
      sensitivity. Neither mutant showed altered sensitivity to ethylene in hypocotyl
      growth inhibition assays. jin1 and jin4 identify genes that modulate the response
      of AtVsp to MeJA in leaves of A. thaliana.

PMID- 12226308
TI  - Tissue-Specific Expression of the Tobacco Mosaic Virus Movement Protein in
      Transgenic Potato Plants Alters Plasmodesmal Function and Carbohydrate
      Partitioning.
AB  - Transgenic potato (Solanum tuberosum) plants expressing the movement protein (MP)
      of tobacco mosaic virus (TMV) under the control of the promoters from the class I
      patatin gene (B33) or the nuclear photosynthesis gene (ST-LS1) were employed to
      further explore the mode by which this viral protein interacts with cellular
      metabolism to change carbohydrate allocation. Dye-coupling experiments
      established that expression of the TMV-MP alters plasmodesmal function in both
      potato leaves and tubers when expressed in the respective tissues. However,
      whereas the size-exclusion limit of mesophyll plasmodesmata was increased to a
      value greater than 9.4 kD, this size limit was smaller for plasmodesmata
      interconnecting tuber parenchyma cells. Starch and sugars accumulated in potato
      leaves to significantly lower levels in plants expressing the TMV-MP under the ST
      LS1 promoter, and rate of sucrose efflux from petioles of the latter was higher
      compared to controls. It is interesting that this effect was expressed only in
      mature plants after tuber initiation. No effect on carbohydrate levels was found
      in plants expressing this protein under the B33 promoter. These results are
      discussed in terms of the mode by which the TMV-MP exerts its influence over
      carbon metabolism and photoassimilate translocation, and the possible role of
      plasmodesmal function in controlling these processes.

PMID- 12226309
TI  - In Vivo and in Vitro Phosphorylation of the Phosphoenolpyruvate Carboxylase from
      Wheat Seeds during Germination.
AB  - Phosphoenolpyruvate carboxylase (PEPC) activity was detected in the aleurone
      endosperm of wheat (Triticum aestivum cv Chinese Spring) seeds, and specific anti
      Sorghum C4 PEPC polyclonal anti-bodies cross-reacted with 103- and 100-kD
      polypeptides present in dry seeds and seeds that had imbibed; in addition, a new,
      108-kD polypeptide was detected 6 h after imbibition. The use of specific anti
      phosphorylation-site immunoglobulin G (APS-IgG) identified the presence of a
      phosphorylation motif equivalent to that found in other plant PEPCs studied so
      far. The binding of this APS-IgG to the target protein promoted changes in the
      properties of seed PEPC similar to those produced by phosphorylation, as
      previously shown for the recombinant Sorghum leaf C4 PEPC. In desalted seed
      extracts, an endogenous PEPC kinase activity catalyzed a bona fide
      phosphorylation of the target protein, as deduced from the immunoinhibition of
      the in vitro phosphorylation reaction by the APS- IgG. In addition, the major,
      103-kD PEPC polypeptide was also shown to be radiolabeled in situ 48 h after
      imbibition in [32P]orthophosphate. The ratio between optimal (pH 8) and
      suboptimal (pH 7.3 or 7.1) PEPC activity decreased during germination, thereby
      suggesting a change in catalytic rate related to an in vivo phosphorylation
      process. These collective data document that the components needed for the
      regulatory phosphorylation of PEPC are present and functional during germination
      of wheat seeds.

PMID- 12226310
TI  - Association of Plant p40 Protein with Ribosomes Is Enhanced When Polyribosomes
      Form during Periods of Active Tissue Growth.
AB  - p40s are acidic proteins of eukaryotic cells occurring either free in the
      cytoplasm or in association with ribosomes, the latter occurring in both
      monosomes and polysomes. p40s may play a role in the regulation of protein
      synthesis, although the exact mechanism is not known. Leaves of all 10 plant
      species examined here, including both monocots and dicots, contained proteins
      detected on immunoblots with Arabidopsis thaliana p40 antiserum. The number and
      apparent size of the protein bands were variable even among closely related
      species. Abundance of p40 relative to ribosomal content during soybean (Glycine
      max L.) seed germination and during seed and leaf development was examined. p40
      abundance correlated with periods of active tissue growth and high polysome
      content. The plant growth regulator indole acetic acid caused an increase in
      polysome formation in etiolated pea (Pisum sativum L.) plants and a concomitant
      recruitment of p40 into polysomes. Subcellular localization at the microscopy
      level indicated that the pattern of p40 staining is very similar to that for RNA,
      except that p40 is excluded from the nucleus. These data suggest that p40 is an
      accessory protein of the ribosome that might play a role in plant growth and
      development.

PMID- 12226311
TI  - Differential Expression of Lipoxygenase Isoenzymes in Embryos of Germinating
      Barley.
AB  - Expression of lipoxygenase was studied in barley (Hordeum distichum L.) embryos
      during germination. Total lipoxygenase activity was high in quiescent grains,
      dropped during the 1st d of germination, and subsequently increased to a level
      similar to that in quiescent grains. The contribution of two isoenzymes,
      lipoxygenases 1 (LOX-1) and 2 (LOX-2), was studied at the activity, protein, and
      mRNA levels. Activity ratios of the two isoforms were determined via the ratio of
      9- and 13-hydroperoxides, which are formed from linoleic acid. Isoenzyme protein
      levels were determined using specific monoclonal antibodies. mRNA levels were
      studied using the specific cDNA probes LoxA and LoxC, which correspond to LOX-1
      and LOX-2, respectively. The major difference in temporal expression of LOX-1 and
      LOX-2 was observed in quiescent grains. At this stage, LOX-1 contributed almost
      exclusively to total lipoxygenase activity. LOX-2 activity rapidly increased
      until d 2 of germination. From this time point onward, LOX-1 and LOX-2 showed
      similar patterns at both activity and protein levels. The tissue distribution of
      the two isoenzymes in the germinating embryo was closely similar, with the
      highest expression levels in leaves and roots. The levels of LOX-1 and LOX-2 may
      be regulated mainly pretranslationally, as suggested by the similarity of the
      protein and mRNA patterns corresponding to the two isoforms.

PMID- 12226313
TI  - Freezing Characteristics of Rigid Plant Tissues (Development of Cell Tension
      during Extracellular Freezing).
AB  - The freezing characteristics and development of cell tension during extracellular
      freezing were examined in supercooling stem tissues of riverbank grapes (Vitis
      riparia) and cold-hardened leaves of live oak (Quercus virginiana) and mountain
      cranberry (Vaccinium vitis-idaea). Dormant stem xylem and pith tissues of river
      bank grapes were resistant to freeze-induced dehydration above the homogeneous
      nucleation temperature, and they developed cell tension reaching a maximum of 27
      MPa. Similarly, extracellular freezing induced cell tension in the leaves of live
      oak and mountain cranberry. Maximum cell tension in the leaves of live oak was
      16.8 MPa and 8.3 MPa in the leaves of mountain cranberry. Following peak tensions
      in the leaves, a decline in the pressure was observed with progressive freezing.
      The results suggest that resistance to cell deformation during extracellular
      freezing due to cell-wall rigidity can lead to reduced cell dehydration and
      increased cell tension. A relationship to predict freezing behavior in plant
      tissues based on cell rigidity is presented. Based on cell-water relations and
      ice nucleation rates, cell-wall rigidity has been shown to effect the freezing
      characteristics of plant tissues, including freeze-induced dehydration,
      supercooling, and homogeneous nucleation temperatures.

PMID- 12226312
TI  - Signals Regulating the Expression of the Nuclear Gene Encoding Alternative
      Oxidase of Plant Mitochondria.
AB  - Suspension cells of tobacco (Nicotiana tabacum L. cv Bright Yellow) were used to
      investigate signals regulating the expression of the nuclear gene Aox1 encoding
      the mitochondrial alternative oxidase (AOX) protein responsible for cyanide
      resistant respiration in plants. We found that an increase in the tricarboxylic
      acid cycle intermediate citrate (either after its exogenous supply to cells or
      after inhibition of aconitase by monofluoroacetate) caused a rapid and dramatic
      increase in the steady-state level of Aox1 mRNA and AOX protein. This led to a
      large increase in the capacity for AOX respiration, defined as the amount of
      salicylhydroxamic acid-sensitive O2 uptake by cells in the presence of potassium
      cyanide. The results indicate that citrate may be an important signal metabolite
      regulating Aox1 gene expression. A number of other treatments were also
      identified that rapidly induced the level of Aox1 mRNA and AOX capacity. These
      included short-term incubation of cells with 10 mM acetate, 2 [mu]M antimycin A,
      5 mM H2O2, or 1 mM cysteine. For some of these treatments, induction of AOX
      occurred without an increase in cellular citrate level, indicating that other
      signals (possibly related to oxidative stress conditions) are also important in
      regulating Aox1 gene expression. The signals influencing Aox1 gene expression are
      discussed with regard to the potential function(s) of AOX to modulate
      tricarboxylic acid cycle metabolism and/or to prevent the generation of active
      oxygen species by the mitochondrial electron transport chain.

PMID- 12226314
TI  - Cell-Wall Changes and Cell Tension in Response to Cold Acclimation and Exogenous
      Abscisic Acid in Leaves and Cell Cultures.
AB  - Freeze-induced cell tensions were determined by cell water relations in leaves of
      broadleaf evergreen species and cell cultures of grapes (Vitis spp.) and apple
      (Malus domestica). Cell tensions increased in response to cold acclimation in
      leaves of broadleaf evergreen species during extracellular freezing, indicating a
      higher resistance to cell volume changes during freezing in cold-hardened leaves
      than in unhardened leaves. Unhardened leaves, typically, did not develop tension
      greater than 3.67 MPa, whereas cold-hardened leaves attained tensions up to 12
      MPa. With further freezing there was a rapid decline and a loss of tension in
      unhardened leaves of all the broadleaf evergreen species studied. Also, similar
      results were observed in cold-hardened leaves of all of the species except in
      those of inkberry (Ilex glabra) and Euonymus fortunei, in which negative
      pressures persisted below -40[deg]C. Abscisic acid treatment of inkberry and
      Euonymus kiautschovica resulted in increases in freeze-induced tensions in
      leaves, suggesting that both cold acclimation and abscisic acid have similar
      effects on freezing behavior[mdash] specifically on the ability of cell walls to
      undergo deformation. Decreases in peak tensions were generally associated with
      lethal freezing injury and may suggest cavitation of cellular water. However, in
      suspension-cultured cells of grapes and apple, no cell tension was observed
      during freezing. Cold acclimation of these cells resulted in an increase in the
      cell-wall strength and a decrease in the limiting cell-wall pore size from 35 to
      22 A in grape cells and from 29 to 22 A in apple cells.

PMID- 12226315
TI  - Specificity of the Organic Acid Activation of Alternative Oxidase in Plant
      Mitochondria.
AB  - The claim that succinate and malate can directly stimulate the activity of the
      alternative oxidase in plant mitochondria (A.M. Wagner, C.W.M. van den Bergen, H.
      Wincencjusz [1995] Plant Physiol 108: 1035-1042) was reinvestigated using sweet
      potato (Ipomoea batatas L.) mitochondria. In whole mitochondria, succinate (in
      the presence of malonate) and both L- and D-malate stimulated respiration via
      alternative oxidase in a pH- (and NAD+)-dependent manner. Solubilized malic
      enzyme catalyzed the oxidation of both L- and D-malate, although the latter at
      only a low rate and only at acid pH. In submitochondrial particle preparations
      with negligible malic enzyme activity, neither L- nor D-malate stimulated
      alternative oxidase activity. However, even in the presence of high malonate
      concentrations, some succinate oxidation was observed via the alternative
      oxidase, giving the impression of stimulation of the oxidase. Neither L-malate
      nor succinate (in the presence of malonate) changed the dependence of alternative
      oxidase activity on ubiquinone reduction state in submitochondrial particles. In
      contrast, a large change in this dependence was observed upon addition of
      pyruvate. Half-maximal stimulation of alternative oxidase by pyruvate occurred at
      less than 5 [mu]M in submitochondrial particles, one-twentieth of that reported
      for whole mitochondria, suggesting that pyruvate acts on the inside of the
      mitochondrion. We suggest that malate and succinate do not directly stimulate
      alternative oxidase, and that reports to the contrary reflect intra-mitochondrial
      generation of pyruvate via malic enzyme.

PMID- 12226316
TI  - The Loss of Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase Caused by 24-Hour
      Rain Treatment Fully Explains the Decrease in the Photosynthetic Rate in Bean
      Leaves.
AB  - Recently, we have found that simulated rainfall causes a chronic inhibition of
      leaf photosynthesis in Phaseolus vulgaris (M. Ishibashi and I. Terashima [1995]
      Plant Cell Environ 18: 431-438). Mechanisms of this inhibition were examined in
      the present study. After the plants were treated with continuous mist for 24 h
      and then dried to unwet conditions, light-saturated photosynthetic rates of the
      leaves measured at 35 Pa ambient CO2 decreased to one-half of the control level.
      The extractable activity of ribulose-1,5-bisphosphate carboxylase/oxygenase
      (Rubisco) also decreased to the same extent. Unexpectedly, this decline was due
      not to the lowered activation state but to the decrease in the amount of Rubisco.
      Before or after the "rain" treatment, the relationship between the net
      photosynthetic rate and the amount of Rubisco was expressed as a unique linear
      function with a small intercept (r2 = 0.84). From these it was inferred that the
      main cause of the rain-induced decline in photo-synthetic rate was the loss in
      amount of Rubisco.

PMID- 12226317
TI  - Ecotype-Specific Expression of a Flowering Mutant Phenotype in Arabidopsis
      thaliana.
AB  - The majority of mutations that delay flowering in Arabidopsis thaliana have been
      identified in studies of the Landsberg erecta (Ler) ecotype. In this report we
      describe a gene (referred to as FLD) that, when mutated, delays flowering in the
      Columbia ecotype but has a minimal phenotype in the Ler genetic background. The
      late-flowering phenotype of fld mutants requires a non-Ler allele of another gene
      involved in the control of flowering time, Flowering Locus C. fld mutants retain
      a photoperiod response, and the flowering time of fld mutants can be reduced by
      cold treatment and low red/far-red light ratios.

PMID- 12226319
TI  - The Electronic Plant Gene Register.

PMID- 12226318
TI  - PIP1 Aquaporins Are Concentrated in Plasmalemmasomes of Arabidopsis thaliana
      Mesophyll.
AB  - The PIP1 subfamily of water channel proteins (aquaporins) constitute about 1% of
      the plasma membrane (PM) proteins from Arabidopsis thaliana leaves. Immunogold
      electron microscopy has confirmed their localization at the PM of mesophyll
      cells. Very high labeling density at PM invaginations known as plasmalemmasomes
      was observed. Therefore, we suggest that these subcellular structures are
      involved in water transport between the apoplast and the vacuole.

PMID- 12226320
TI  - The Mechanism of Ethylene Perception.

PMID- 12226321
TI  - NaCl-Induced Alterations in Both Cell Structure and Tissue-Specific Plasma
      Membrane H+ -ATPase Gene Expression.
AB  - NaCl-induced plasma membrane H+-ATPase gene expression, which occurs in roots and
      fully expanded leaves of the halophyte Atriplex nummularia L. (X. Niu, M.L.
      Narasimhan, R.A. Salzman, R.A. Bressan, P.M. Hasegawa [1993] Plant Physiol 103:
      713-718), has been differentially localized to specific tissues using in situ RNA
      hybridization techniques. Twenty-four-hour exposure of plants to 400 mM NaCl
      resulted in substantial accumulation of H+ pump message in the epidermis of the
      root tip and the endodermis of the root elongation/differentiation zone. In
      expanded leaves, NaCl induction of plasma membrane H+-ATPase message accumulation
      was localized to bundle-sheath cells. Ultrastructural analyses indicated that
      significant cytological adaptations in root cells included plasmolysis that is
      accompanied by plasma membrane invaginations, formation of Hechtian strands and
      vesiculation, and vacuolation. These results identify specific tissues that are
      involved in the regulation of Na+ and Cl- uptake into different organs of the
      halophyte A. nummularia and provide evidence of the intercellular and interorgan
      coordination that occurs in the mediation of NaCl adaptation.

PMID- 12226322
TI  - Effect of Cold Hardening on the Components of Respiratory Decarboxylation in the
      Light and in the Dark in Leaves of Winter Rye.
AB  - In the dark, all decarboxylation reactions are associated with the oxidase
      reactions of mitochondrial electron transport. In the light, photorespiration is
      also active in photosynthetic cells. In winter rye (Secale cereale L.), cold
      hardening resulted in a 2-fold increase in the rate of dark respiratory CO2
      release from leaves compared with nonhardened (NH) controls. However, in the
      light, NH and cold-hardened (CH) leaves had comparable rates of oxidase
      decarboxylation and total intracellular decarboxylation. Furthermore, whereas CH
      leaves showed similar rates of total oxidase decarboxylation in the dark and
      light, NH leaves showed a 2-fold increase in total oxidase activity in the light
      compared with the dark. Light suppressed oxidase decarboxylation of end products
      of photosynthesis 2-fold in NH leaves and 3-fold in CH leaves in air. However, in
      high-CO2, light did not suppress the oxidase decarboxylation of end products.
      Thus, the decrease in oxidase decarboxylation of end products observed in the
      light and in air reflected glycolate-cycle-related inhibition of tricarboxylic
      acid cycle activity. We also showed that the glycolate cycle was involved in the
      decarboxylation of the end products of photosynthesis in both NH and CH leaves,
      suggesting a flow of fixed carbon out of the starch pool in the light.

PMID- 12226323
TI  - Growth Inhibition in Suspension-Cultured Rice Cells under Phosphate Deprivation
      Is Mediated through Putrescine Accumulation.
AB  - The effects of phosphate deprivation on the growth and polyamine levels of
      suspension-cultured rice (Oryza sativa) cells were investigated. When rice
      suspension cells were deprived of phosphate, cell growth was markedly inhibited.
      Phosphate deprivation resulted in a higher putrescine level and lower spermidine
      and spermine levels in rice suspension cells. The growth of rice cells cultured
      in the absence of phosphate did not recover as a result of spermidine and
      spermine addition. D-Arginine and [alpha]-methylornithine, inhibitors of
      putrescine biosynthesis, caused a reduced level of putrescine in rice suspension
      cells cultured under phosphate deprivation. The growth of rice cells cultured in
      the absence of phosphate was completely recovered after the addition of D
      arginine but not [alpha]-methylornithine. Our results indicate that putrescine
      accumulation is a factor causing growth inhibition of suspension-cultured rice
      cells under phosphate deprivation.

PMID- 12226324
TI  - Antisense RNA Inhibition of RbcS Gene Expression Reduces Rubisco Level and
      Photosynthesis in the C4 Plant Flaveria bidentis.
AB  - The C4 dicot Flaveria bidentis was genetically transformed with an antisense RNA
      construct targeted to the nuclear-encoded gene for the small subunit of ribulose
      1,5-bisphosphate carboxylase/oxygenase (Rubisco; RbcS). RbcS mRNA levels in
      leaves of transformants were reduced by as much as 80% compared to wild-type
      levels, and extractable enzyme activity was reduced by up to 85%. There was no
      significant effect of transformation with the gene construct on levels of other
      photosynthetic enzymes. Antisense transformants with reduced Rubisco activity
      exhibited a stunted phenotype. Rates of photosynthesis were reduced in air at
      high light and over a range of CO2 concentrations but were unaffected at low
      light. From these results we conclude that, as is the case in C3 plants, Rubisco
      activity is a major determinant of photosynthetic flux in C4 plants under high
      light intensities and air levels of CO2.

PMID- 12226325
TI  - Germin Gene Expression Is Induced in Wheat Leaves by Powdery Mildew Infection.
AB  - Germin gene expression is induced in wheat (Triticum aestivum L.) leaves by
      powdery mildew (Erysiphe graminis f. sp. tritici) infection. Germin is a protein
      marker for early cereal development and is an oxalate oxidase, an enzyme that
      catalyzes the conversion of oxalate to CO2 and H2O2. The induction of germin gene
      expression by powdery mildew infection is consistent with the importance of H2O2
      to plant defense and identifies a mechanism for the elevation of H2O2 levels in
      wheat leaves. Germin mRNA levels increased 2 d after inoculation of seedlings
      with powdery mildew and continued to increase throughout an 8-d time course. The
      increase in accumulation of germin mRNA was accompanied by an increase in the
      germin oligomer, which reached maximal levels by d 6. An increase in oxalate
      oxidase activity paralleled germin oligomer accumulation. Germin gene expression
      was induced in a relatively resistant cultivar (Bobwhite) as well as in a
      susceptible cultivar (Cheyenne), suggesting that the induction of germin gene
      expression is an indicator of powdery mildew infection rather than cultivar
      resistance.

PMID- 12226326
TI  - Identification of Antheridiogens in Lygodium circinnatum and Lygodium flexuosum.
AB  - Antheridiogens in two species of Schizaeaceous ferns, Lygodium circinnatum and
      Lygodium flexuosum, were analyzed by gas chromatography-mass spectrometry. In L.
      circinnatum, gibberellin A73 (GA73) methyl ester (GA73-Me), which had originally
      been identified in L. japonicum, was identified as a principal antheridiogen, and
      the methyl esters of five known GAs (GA9, GA20, GA70, GA88, and 3-epi-GA88) were
      also identified as minor antheridiogens. In addition, four compounds
      corresponding to isomers of monohydroxy-GA73-Me were detected. One of these was
      shown to be 12[beta]-hydroxy-GA73-Me, the parent acid of which has been allocated
      the GA assignment GA96. The other three compounds, tentatively named X1, X2, and
      X3, have not been fully characterized. In L. flexuosum, GA73-Me was also
      identified as a major antheridiogen, with X2 being detected as a minor one. The
      total antheridium-formation activity in the culture medium of 7-week-old
      prothallia of L. circinnatum and L. flexuosum was more than 1000 times higher
      than that of L. japonicum. On the other hand, the response of gametophytes of the
      former two Lygodium ferns to GA73-Me was more than 100 times lower than that of
      L. japonicum.

PMID- 12226327
TI  - Biosynthesis of Caffeine in Leaves of Coffee.
AB  - The levels of endogenous caffeine and theobromine were much higher in buds and
      young leaves of Coffea arabica L. cv Kent than in fully developed leaves.
      Biosynthesis of caffeine from 14C-labeled adenine, guanine, xanthosine, and
      theobromine was observed, whereas other studies (H. Ashihara, A.M. Monteiro, T.
      Moritz, F.M. Gillies, A. Crozier [1996] Planta 198: 334-339) have indicated that
      there is no detectable incorporation of label into caffeine when theophylline and
      xanthine are used as substrates for in vivo feeds with leaves of C. arabica. The
      capacity for caffeine biosynthesis, especially from guanine and xanthosine, was
      reduced markedly in both fully developed mature and aged leaves. Data obtained in
      pulse-chase experiments with young leaves indicate the operation of an AMP -> IMP
      -> xanthosine 5[prime]-monophosphate (or GMP -> guanosine) -> xanthosine -> 7
      methylxanthosine -> 7-methylxanthine -> theobromine -> caffeine pathway. The data
      obtained provide strong evidence against proposals by G.M. Nazario and C.J.
      Lovatt ([1993] Plant Physiol 103: 1203-1210) concerning the independence of
      caffeine and theobromine biosynthesis pathways and the role of xanthine as a key
      intermediate in caffeine biosynthesis.

PMID- 12226328
TI  - Influence of Salicylic Acid on the Induction of Competence for H2O2 Elicitation
      (Comparison of Ergosterol with Other Elicitors).
AB  - Hypocotyls from etiolated cucumber (Cucumis sativus L.) seedlings were gently
      abraded at their epidermal surface, and cut segments were used to study the rapid
      and transient elicitation of H2O2 by ergosterol, chitosan, mastoparan, and a
      polymeric fungal elicitor. Freshly abraded segments were only barely competent
      for any H2O2 production, but they developed this competence subsequent to
      abrasion. This process was enhanced by 2,6-dichloroisonicotinic acid and
      salicylic acid, which induced acquired resistance to fungal penetration in the
      epidermal cells. Enhancement of competence induction by salicylic acid was also
      evident for spontaneous H2O2 production and differed in degree for the various
      elicitors, indicating that mainly the enzyme complex producing H2O2, but also
      other components of the elicitation system, improved. Ergosterol, chitosan, and
      fungal elicitor also rendered the segments refractory to a second stimulation by
      the same compound, whereas mastoparan was inactive in this respect. The four
      elicitors also differed markedly in their ability to diminish or enhance H2O2
      production by a second treatment with a different elicitor, indicating that
      several sites of the H2O2 elicitation system are subject to short-term
      regulation.

PMID- 12226329
TI  - Cercospora beticola Toxins (X. Inhibition of Plasma Membrane H+-ATPase by
      Beticolin-1).
AB  - Beticolin-1 is a toxin produced by the fungus Cercospora beticola. The chemical
      structure of this toxin was previously elucidated. The effects of beticolin-1 on
      purified corn root plasma membrane H+-ATPase were studied in a solubilized form
      or were reconstituted into liposome membranes. The ATP hydrolysis activity of the
      purified solubilized enzyme was inhibited by micromolar concentrations of
      beticolin-1, and this inhibition was noncompetitive with respect to ATP. When
      this purified enzyme was inserted into liposome membranes, a competitive
      inhibition of the H+-ATPase hydrolysis activity by beticolin-1 was observed. The
      effect of beticolin-1 on the formation of H+-ATPase-phosphorylated intermediate
      was also studied. With the purified enzyme in its solubilized form, the level of
      phosphorylated intermediate was not affected by the presence of beticolin-1,
      whereas micromolar concentrations of the toxin led to a marked inhibition of its
      formation when the enzyme was reconstituted into liposomes. These data suggest
      that (a) the plasma membrane H+-ATPase is a direct target for beticolin-1, and
      (b) the kinetics of inhibition and the effect on the phosphorylated intermediate
      are linked and both depend on the lipid environment of the enzyme.

PMID- 12226330
TI  - Oxidative Stress Induces Partial Degradation of the Large Subunit of Ribulose-1,5
      Bisphosphate Carboxylase/Oxygenase in Isolated Chloroplasts of Barley.
AB  - The effects of oxidative stress on the degradation of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco; EC 4.1.1.39) were studied in isolated
      chloroplasts from barley (Hordeum vulgare L. cv Angora). Active oxygen (AO) was
      generated by varying the light intensity, the oxygen concentration, or the
      addition of herbicides or ADP-FeCl3-ascorbate to the medium. Oxidative treatments
      stimulated association of Rubisco with the insoluble fraction of chloroplasts and
      partial proteolysis of the large subunit (LSU). The most prominent degradation
      product of the LSU of Rubisco showed an apparent molecular mass of 36 kD. The
      data suggest that an increase in the amount of AO photogenerated by O2 reduction
      at photosystem I triggers Rubisco degradation. A possible relationship between AO
      mediated denaturation of Rubisco and proteolysis of the LSU is discussed.

PMID- 12226331
TI  - Intracellular Levels of Free Linolenic and Linoleic Acids Increase in Tomato
      Leaves in Response to Wounding.
AB  - An intracellular signaling pathway for activating plant defense genes against
      attacking herbivores and pathogens is mediated by a lipid-based signal
      transduction cascade. In this pathway, linolenic acid (18:3) is proposed to be
      liberated from cell membranes and is converted to cyclopentanones that are
      involved in transcriptional regulation of defense genes, analogously to
      prostaglandin synthesis and function in animals. Levels of 18:3 and linoleic acid
      in tomato (Lycopersicon esculentum) leaves increased within 1 h when the leaves
      were wounded with a hemostat across the main vein to simulate herbivore attacks.
      The increase correlated with the time course of accumulation of jasmonic acid, a
      cyclopentanone product of 18:3, that had previously been shown to increase in
      leaves in response both to wounding and to elicitors of plant defense genes. One
      hour after wounding, at least a 15-fold excess of 18:3 was found over that
      required to account for the levels of newly synthesized jasmonic acid. The free
      fatty acids in both control and wounded leaves accounted for less than 0.25% of
      the total fatty acids. However, the total lipid contents of the leaves remained
      relatively unchanged up to 8 h after wounding, indicating that extensive loss of
      lipids did not occur, although a gradual decrease in polar lipids was observed,
      mainly in monogalactosyl diacylglycerol of chloroplast lipids. The data support a
      role for lipid release as a key step in the signaling events that activate
      defense genes in tomato leaves in response to wounding by attacking herbivores.

PMID- 12226333
TI  - Chloroplast Movement in the Shade Plant Tradescantia albiflora Helps Protect
      Photosystem II against Light Stress.
AB  - The role of high-light-induced chloroplast movement in the photoprotection of the
      facultative shade plant Tradescantia albiflora was investigated by comparison
      with pea (Pisum sativum L.) leaves, both grown in 50 [mu]mol photons m-2 s-1.
      Photoinactivation of photosystem II (PSII) in vivo was induced in 1.1% CO2 by
      varying either duration (0-2 h) of illumination (fixed at 1800 [mu]mol m-2 s-1)
      or irradiance (0-3000 [mu]mol m-2 s-1) at a fixed duration (1 h) after
      infiltration of leaves with water or lincomycin (an inhibitor of chloroplast
      encoded protein synthesis). At all photon exposures, PSII of T. albiflora leaves
      showed a greater resistance to light stress than pea leaves, although both
      utilization of absorbed light by photosynthesis and psbA gene product synthesis
      were smaller than for pea leaves. This greater tolerance was not due to
      differences in PSII antenna size or the index of susceptibility of PSII to light
      stress, because these two parameters were comparable in both plants. However, the
      transmittance increase mediated by chloroplast movement was greater in T.
      albiflora than pea, resulting in a 10% decrease of absorbed light at high light.
      We suggest that the greater tolerance of PSII against light stress in T.
      albiflora may be partly ascribed to its light-induced chloroplast rearrangement.

PMID- 12226332
TI  - Isolation of a Microsomal Enzyme System Involved in Glucosinolate Biosynthesis
      from Seedlings of Tropaeolum majus L.
AB  - An in vitro system that converts phenylalanine to phenylacetaldoxime in the
      biosynthesis of the glucosinolate glucotropaeolin has been established in
      seedlings of Tropaeolum majus L. exposed to the combined treatment of jasmonic
      acid, ethanol, and light. The treatment resulted in a 9-fold induction, compared
      with untreated, dark-grown seedlings, of de novo biosynthesis measured as
      incorporation of radioactively labeled phenylalanine into glucotropaeolin.
      Formation of the inhibitory degradation product benzylisothiocyanate during
      tissue homogenization was prevented by inactivation of the thioglucosidase
      myrosinase by addition of 100 mM ascorbic acid to the isolation buffer. This
      allowed the isolation of a biosynthetically active microsomal preparation from
      the induced T. majus plant material. The enzyme, which catalyzes the conversion
      of phenylalanine to the corresponding oxime, was sensitive to cytochrome P450
      inhibitors, indicating the involvement of a cytochrome P450 in the biosynthetic
      pathway. It has previously been shown that the oxime-producing enzyme in the
      biosynthesis of p-hydroxybenzylglucosinolate in Sinapis alba L. is dependent on
      cytochrome P450, whereas the oxime-producing enzymes in Brassica species have
      been suggested to be flavin monooxygenases or peroxidase-type enzymes. The result
      with T. majus provides additional experimental documentation for a similarity
      between the enzymes converting amino acids into the corresponding oximes in the
      biosynthesis of glucosinolates and cyanogenic glucosides.

PMID- 12226334
TI  - Relationship between Active Oxygen Species, Lipid Peroxidation, Necrosis, and
      Phytoalexin Production Induced by Elicitins in Nicotiana.
AB  - Excised leaves of Nicotiana tabacum var Xanthi and Nicotiana rustica were treated
      with cryptogein and capsicein, basic and acidic elicitins, respectively. Both
      compounds induced leaf necrosis, the intensity of which depended on concentration
      and duration of treatment. N. tabacum var Xanthi was the most sensitive species
      and cryptogein was the most active elicitin. Lipid peroxidation in elicitin
      treated Nicotiana leaves was closely correlated with the appearance of necrosis.
      Elicitin treatments induced a rapid and transient burst of active oxygen species
      (AOS) in cell cultures of both Nicotiana species, with the production by Xanthi
      cells being 6-fold greater than that by N. rustica. Similar maximum AOS
      production levels were observed with both elicitins, but capsicein required 10
      fold higher concentrations than those of cryptogein. Phytoalexin production was
      lower in response to both elicitins in N. tabacum var Xanthi cells than in N.
      rustica cells, and capsicein was the most efficient elicitor of this response. In
      cryptogein-treated cell suspensions, phytoalexin synthesis was unaffected by
      diphenyleneiodonium, which inhibited AOS generation, nor was it affected by tiron
      or catalase, which suppressed AOS accumulation in the extracellular medium. These
      results suggest that AOS production, lipid peroxidation, and necrosis are
      directly related, whereas phytoalexin production depends on neither the presence
      nor the intensity of these responses.

PMID- 12226335
TI  - Iron Uptake by Symbiosomes from Soybean Root Nodules.
AB  - To identify possible iron sources for bacteroids in planta, soybean (Glycine max
      L. Merr.) symbiosomes (consisting of the bacteroid-containing peribacteroid space
      enclosed by the peribacteroid membrane [PBM]) and bacteroids were assayed for the
      ability to transport iron supplied as various ferric [Fe(III)]-chelates. Iron
      presented as a number of Fe(III)-chelates was transported at much higher rates
      across the PBM than across the bacteroid membranes, suggesting the presence of an
      iron storage pool in the peribacteroid space. Pulse-chase experiments confirmed
      the presence of such an iron storage pool. Because the PBM is derived from the
      plant plasma membrane, we reasoned that it may possess a ferric-chelate reductase
      activity similar to that present in plant plasma membrane. We detected ferric
      chelate reductase activity associated with the PBM and suggest that reduction of
      Fe(III) to ferrous [Fe(II)] plays a role in the movement of iron into soybean
      symbiosomes.

PMID- 12226336
TI  - Potamogeton pectinatus Is Constitutively Incapable of Synthesizing Ethylene and
      Lacks 1-Aminocyclopropane-1-Carboxylic Acid Oxidase.
AB  - A highly sensitive laser-driven photoacoustic detector responsive to [less than
      or equal to]2.1 nmol m-3 ethylene (50 parts per trillion [v/v]) was used for
      ethylene analysis. Dark-grown plants of Potamogeton pectinatus L. growing from
      small tubers made no ethylene. Exposure of shoots to white light, wounding,
      submergence in water followed by desubmergence, partial oxygen shortage, indole
      acetic acid, or carbon dioxide failed to induce ethylene production, although
      clear effects were observed in Pisum sativum L. Some ethylene was released after
      applying high concentrations of the ethylene precursor 1-aminocyclopropane-1
      carboxylic acid (ACC; 10 mol m-3) to P. pectinatus, but the amount was trivial
      compared with that released by P. sativum. More endogenous ACC was found in P.
      pectinatus than in P. sativum. Considerable ACC oxidase activity was present in
      tissue extracts of P. sativum. However, no ACC oxidase activity was found in P.
      pectinatus, indicating that this is where ethylene production is arrested.

PMID- 12226337
TI  - The Effect of Elevated [CO2] on Growth and Photosynthesis of Two Eucalyptus
      Species Exposed to High Temperatures and Water Deficits.
AB  - Two species of eucalyptus (Eucalyptus macrorhyncha and Eucalyptus rossii) were
      grown for 8 weeks in either ambient (350 [mu]L L-1) or elevated (700 [mu]L L-1)
      CO2 concentrations, either well watered or without water additions, and subjected
      to a daily, 3-h high-temperature (45[deg]C, maximum) and high-light (1250 [mu]mol
      photons m-2 s-1, maximum) stress period. Water-stressed seedlings of E.
      macrorhyncha had higher leaf water potentials when grown in elevated [CO2].
      Growth analysis indicated that increased [CO2] may allow eucalyptus species to
      perform better during conditions of low soil moisture. A down-regulation of
      photosynthetic capacity was observed for seedlings grown in elevated [CO2] when
      well watered but not when water stressed. Well-watered seedlings grown in
      elevated [CO2] had lower quantum efficiencies as measured by chlorophyll
      fluorescence (the ratio of variable to maximal chlorophyll fluorescence [Fv/Fm])
      than seedlings grown in ambient [CO2] during the high-temperature stress period.
      However, no significant differences in Fv/Fm were observed between CO2 treatments
      when water was withheld. The reductions in dark-adapted Fv/Fm for plants grown in
      elevated [CO2] were not well correlated with increased xanthophyll cycle
      photoprotection. However, reductions in the Fv/Fm were correlated with increased
      levels of nonstructural carbohydrates. The reduction in quantum efficiencies for
      plants grown in elevated [CO2] is discussed in the context of feedback inhibition
      of electron transport associated with starch accumulation and variation in sink
      strength.

PMID- 12226338
TI  - Synthesis and Turnover of Cell-Wall Polysaccharides and Starch in Photosynthetic
      Soybean Suspension Cultures.
AB  - Soybean (Glycine max [L.] Merr.) suspension cultures grown under photoautotrophic
      and photomixotrophic (1% sucrose) culture conditions were used in 14CO2 pulse
      chase experiments to follow cell-wall polysaccharide and starch biosynthesis and
      turnover. Following a 30-min pulse with 14CO2, about one-fourth of the 14C of the
      photoautotrophic cells was incorporated into the cell wall; this increased to
      about 80% during a 96-h chase in unlabeled CO2. Cells early in the cell culture
      cycle (3 d) incorporated more 14C per sample and also exhibited greater turnover
      of the pectin and hemicellulose fractions as shown by loss of 14C during the 96-h
      chase than did 10- and 16-d cells. When the chase occurred in the dark, less 14C
      was incorporated into the cell wall because of the cessation of growth and higher
      respiratory loss. The dark effect was much less pronounced with the
      photomixotrophic cells. Even though the cell starch levels were much lower than
      in leaves, high 14C incorporation was found during the pulse, especially in older
      cells. The label was largely lost during the chase, indicating that starch is
      involved in the short-term storage of photosynthate. Thus, these easily labeled
      and manipulated photosynthetic cells demonstrated extensive turnover of the cell
      wall pectin and hemicellulose fractions and starch during the normal growth
      process.

PMID- 12226339
TI  - Changes in Dehydrodiferulic Acids and Peroxidase Activity against Ferulic Acid
      Associated with Cell Walls during Growth of Pinus pinaster Hypocotyl.
AB  - Hydroxycinnamic acids associated with hypocotyl cell walls of dark-grown
      seedlings of Pinus pinaster Aiton were extracted with 1 N NaOH and identified by
      gas chromatography-mass spectrometry. The main hydroxycinnamic acid found was
      ferulic acid. Diferulic acid dehydrodimers were also found, with the 8,8-coupled
      isomer (compound 11) being the dehydrodiferulate present in the highest amount.
      However, the 5,5-coupled isomer, commonly referred to referred to as diferulic
      acid, was not detected. Two truxillic acids, 4-4[prime]-dihydroxy-3-3[prime]
      dimethoxy-[alpha]-truxillic acids I and II, were tentatively identified. The 8,8
      coupled dehydrodiferulic acid (compound 11) was the phenolic acid that showed the
      most conspicuous changes with hypocotyl age as well as along the hypocotyl axis.
      Peroxidase activity against ferulic acid was found in the apoplastic fluid as
      well as being ionically and covalently bound to the cell walls. The peroxidase
      activity increased with hypocotyl age as well as from the subapical toward the
      basal region of the hypocotyls. A key role in the cell-wall stiffening of 8,8 but
      not 5,5 dimerization of ferulic acid catalyzed by cell-wall peroxidases is
      proposed.

PMID- 12226340
TI  - Roots Redefined: Anatomical and Genetic Analysis of Root Development.

PMID- 12226341
TI  - Evidence That the Pathway of Dimethylsulfoniopropionate Biosynthesis Begins in
      the Cytosol and Ends in the Chloroplast.
AB  - In the flowering plant Wollastonia biflora (L.) DC. the first step in 3
      dimethylsulfoniopropionate (DMSP) synthesis is conversion of methionine to S
      methylmethionine (SMM) and the last is oxidation of 3
      dimethylsulfoniopropionaldehyde (DMSP-ald) (F. James, L. Paquet, S.A. Sparace,
      D.A. Gage, A.D. Hanson [1995] Plant Physiol 108: 1439-1448). DMSP-ald was shown
      to undergo rapid, spontaneous decomposition to dimethylsulfide and acrolein.
      However, it was stable enough (half-life [greater than or equal to] 1 h) in
      tertiary amine buffers to use as a substrate for enzyme assays. A dehydrogenase
      catalyzing DMSP-ald oxidation was detected in extracts of W. biflora mesophyll
      protoplasts. This enzyme had a high affinity for DMSP-ald (Km = 1.5 [mu]M), was
      subject to substrate inhibition, preferred NAD to NADP, and was immunologically
      related to plant betaine aldehyde dehydrogenases. After fractionation of
      protoplast lysates, [greater than or equal to]90% of DMSP-ald dehydrogenase
      activity was recovered from the chloroplast stromal fraction, whereas the enzyme
      that mediates SMM synthesis, S-adenosylmethionine:methionine S-methyltransferase,
      was found exclusively in the cytosolic fraction. Immunohistochemical analysis
      confirmed that the S-methyltransferase was cytosolic. Intact W. biflora
      chloroplasts were able to metabolize supplied [35S]SMM to [35S]DMSP. These
      findings indicate that SMM is made in the cytosol, imported into the chloroplast,
      and there converted successively to DMSP-ald and DMSP.

PMID- 12226342
TI  - A Spatial Analysis of Physiological Changes Associated with Infection of
      Cotyledons of Marrow Plants with Cucumber Mosaic Virus.
AB  - Changes in host primary metabolism associated with the compatible interaction
      between cucumber mosaic virus and cotyledons of the marrow plant (Cucurbita pepo
      L.) have been localized, first by measuring activities of key enzymes in infected
      and uninfected regions of the cotyledon, and second by histochemical techniques
      applied to tissue prints of the infected region. A series of progressive
      metabolic changes occurs within the expanding infected lesion. Virus replication
      and the synthesis of viral protein at the periphery creates a strong sink demand
      associated with increased activities of anaplerotic enzymes, increased
      photosynthesis, and starch accumulation. Inside the lesion, when the synthesis of
      virus has declined, photosynthesis is reduced, starch is mobilized, and the
      emphasis of metabolism is shifted toward glycolysis and mitochondrial
      respiration. These changes are associated spatially with the onset of chlorosis.
      A decrease in total protein synthesis in this inner zone could be instrumental in
      some or all of these changes, leading to symptoms of viral infection.

PMID- 12226343
TI  - Photosynthetic Gene Expression in Meristems and during Initial Leaf Development
      in a C4 Dicotyledonous Plant.
AB  - Immunolocalization and fluorescent in situ hybridization were used with confocal
      microscopy to examine patterns of photosynthetic gene expression during initial
      stages of leaf development in the C4 dicot Amaranthus hypochondriacus. mRNAs
      encoding the large and small subunit of ribulose-1,5-bisphosphate carboxylase
      were present in the apical dome and in all cells of the leaf primordia. In
      contrast, these polypeptides were detected only in cells of the ground meristem,
      with no accumulation detected in the apical dome or in other leaf primordia
      cells. The ribulose-1,5-bisphosphate carboxylase transcripts showed very little
      cell-type specificity as leaf structures began to differentiate, whereas their
      polypeptides accumulated primarily in bundle-sheath precursor cells.
      Phosphoenolpyruvate carboxylase and pyruvate orthophosphate dikinase mRNAs were
      abundant in meristems and leaf primordia, although their corresponding
      polypeptides did not accumulate in leaves until the leaf vascular system began to
      differentiate. These polypeptides were mostly restricted to premesophyll cells
      from their earliest detection, whereas their transcripts remained present in
      nearly all leaf cells. These findings indicate that individual C4 genes are
      independently regulated as they become initially localized to their appropriate
      cell types. Furthermore, posttranscriptional regulation plays a major role in
      determining early patterns of C4 gene expression.

PMID- 12226344
TI  - Sucrose Phosphate Synthase Expression at the Cell and Tissue Level Is Coordinated
      with Sucrose Sink-to-Source Transitions in Maize Leaf.
AB  - Immunohistological analyses for sucrose phosphate synthase (SPS) show that the
      protein is localized in both bundle-sheath cells (BS) and mesophyll cells (M) in
      maize (Zea mays) leaves. In young leaves, SPS protein was predominantly in the
      BS, whereas mature leaves showed nearly equal levels of signal in both BS and M.
      A cell-type-specific response was also seen in light and dark treatments. Dark
      treatments led to reduced signal in M; however, little or no change was detected
      in BS. We suggest that SPS in BS is engaged in sucrose biosynthesis by both
      photoassimilatory and starch turnover reactions in maize leaves. In addition, we
      suggest that the enzyme in BS may play a major role in the early biosynthesis of
      sucrose in young leaves. These cell-specific changes in expression in situ were
      in agreement with the estimates of extractable enzyme activity from isolated BS
      and M of mature leaves (R. Ohsugi, S.C. Huber [1987] Plant Physiol 84: 1096
      1101). In contrast, western blot analyses did not show any significant changes in
      the levels of SPS protein in either young or mature leaves subsequent to similar
      dark treatments. It is interesting that the northern blot analyses indicate that
      the steady-state levels of SPS transcripts were markedly reduced after dark
      treatments of > 12 h. Overall, our results indicate that Sps gene expression in
      maize leaf is modulated at multiple levels of controls by both developmental and
      environmental factors.

PMID- 12226345
TI  - Changes in Stomatal Behavior and Guard Cell Cytosolic Free Calcium in Response to
      Oxidative Stress.
AB  - We have investigated the cellular basis for the effects of oxidative stress on
      stomatal behavior using stomatal bioassay and ratio photometric techniques. Two
      oxidative treatments were employed in this study: (a) methyl viologen, which
      generates superoxide radicals, and (b) H2O2. Both methyl viologen and H2O2
      inhibited stomatal opening and promoted stomatal closure. At concentrations [less
      than or equal to]10-5 M, the effects of methyl viologen and H2O2 on stomatal
      behavior were reversible and were abolished by 2 mM EGTA or 10 [mu]M verapamil.
      In addition, at 10-5 M, i.e. the maximum concentration at which the effects of
      the treatments were prevented by EGTA or verapamil, methyl viologen and H2O2
      caused an increase in guard cell cytosolic free Ca2+ ([Ca2+]i), which was
      abolished in the presence of EGTA. Therefore, at low concentrations of methyl
      viologen and H2O2, removal of extracellular Ca2+ prevented both the oxidative
      stress-induced changes in stomatal aperture and the associated increases in
      [Ca2+]i. This suggests that in this concentration range the effects of the
      treatments are Ca2+-dependent and are mediated by changes in [Ca2+]i. In
      contrast, at concentrations of methyl viologan and H2O2 > 10-5 M, EGTA and
      verapamil had no effect. However, in this concentration range the effects of the
      treatments were irreversible and correlated with a marked reduction in membrane
      integrity and guard cell viability. This suggests that at high concentrations the
      effects of methyl viologen and H2O2 may be due to changes in membrane integrity.
      The implications of oxidative stress-induced increases in [Ca2+]i and the
      possible disruption of guard-cell Ca2+ homeostasis are discussed in relation to
      the processes of Ca2+-based signal transduction in stomatal guard cells and the
      control of stomatal aperture.

PMID- 12226346
TI  - Molecular Characterization of the Rehydration Process in the Resurrection Plant
      Craterostigma plantagineum.
AB  - The resurrection plant Craterostigma plantagineum is unique among higher plants
      because it is able to survive a desiccation treatment. For this reason it has
      been used as a model system for the analysis of the molecular mechanisms of
      desiccation tolerance. Many transcripts and proteins are expressed de novo during
      dehydration. This paper describes the molecular events that occur during the
      rehydration process of dried C. plantagineum plants. Changes in gene expression
      patterns were first analyzed by in vivo labeling and in vitro translation
      experiments. In a second set of experiments steady-state mRNA levels were
      monitored using specific cDNA clones. The experiments indicated three major
      changes on the molecular level during rehydration: the dehydration-specific gene
      products disappeared during an early phase of rehydration, a small number of
      rehydration-specific transcripts were synthesized around 12 to 15 h after the
      onset of rewatering, and hydration-related gene products appeared concomitantly.
      The gene expression patterns during rehydration are discussed with respect to the
      possible roles of the gene products.

PMID- 12226347
TI  - Central Roles for Potassium and Sucrose in Guard-Cell Osmoregulation.
AB  - Osmoregulation in guard cells of intact, attached Vicia faba leaves grown under
      growth chamber and greenhouse conditions was studied over a daily light cycle of
      stomatal movements. Under both growth conditions guard cells had two distinct
      osmoregulatory phases. In the first (morning) phase, opening was correlated with
      K+ uptake and, to a lesser extent, sucrose accumulation. In the second
      (afternoon) phase, in which apertures were maximal, K+ content declined and
      sucrose became the dominant osmoticum. Reopening of the stomata after a CO2
      induced closure was accompanied by accumulation of either K+ or sucrose,
      depending on the time of day, indicating that a single environmental signal may
      use multiple osmoregulatory pathways. Malate accumulation, correlated with K+
      uptake, was detected under growth chamber but not greenhouse conditions, whereas
      Cl- was the main K+ counterion in the greenhouse. These results indicate that
      guard-cell osmoregulation in the intact leaf depends on at least two different
      osmoregulatory pathways, K+ transport and sucrose metabolism. Furthermore, the
      relative importance of the K+ counterions malate and Cl- appears to be
      environment-dependent.

PMID- 12226348
TI  - Analysis of the Expression of Anthocyanin Pathway Genes in Developing Vitis
      vinifera L. cv Shiraz Grape Berries and the Implications for Pathway Regulation.
AB  - Anthocyanin synthesis in Vitis vinifera L. cv Shiraz grape berries began 10 weeks
      postflowering and continued throughout berry ripening. Expression of seven genes
      of the anthocyanin biosynthetic pathway (phenylalanine ammonia lyase [PAL],
      chalcone synthase [CHS], chalcone isomerase [CHI], flavanone-3-hydroxylase [F3H],
      dihydroflavonol 4-reductase [DFR], leucoanthocyanidin dioxygen-ase [LDOX], and
      UDP glucose-flavonoid 3-o-glucosyl transferase [UFGT]) was determined. In flowers
      and grape berry skins, expression of all of the genes, except UFGT, was detected
      up to 4 weeks postflowering, followed by a reduction in this expression 6 to 8
      weeks postflowering. Expression of CHS, CHI, F3H, DFR, LDOX, and UFGT then
      increased 10 weeks postflowering, coinciding with the onset of anthocyanin
      synthesis. In grape berry flesh, no PAL or UFGT expression was detected at any
      stage of development, but CHS, CHI, F3H, DFR, and LDOX were expressed up to 4
      weeks postflowering. These results indicate that the onset of anthocyanin
      synthesis in ripening grape berry skins coincides with a coordinated increase in
      expression of a number of genes in the anthocyanin biosynthetic pathway,
      suggesting the involvement of regulatory genes. UFGT is regulated independently
      of the other genes, suggesting that in grapes the major control point in this
      pathway is later than that observed in maize, petunia, and snapdragon.

PMID- 12226349
TI  - Complexity and Genetic Variability of Heat-Shock Protein Expression in Isolated
      Maize Microspores.
AB  - The expression of heat-shock proteins (HSPs) in isolated maize (Zea mays L.)
      microspores has been investigated using high-resolution two-dimensional
      electrophoresis coupled to immunodetection and fluorography of in vivo
      synthesized proteins. To this end, homogeneous and viable populations of
      microspores have been purified in sufficient amounts for molecular analysis from
      plants grown in controlled conditions. Appropriate conditions for thermal stress
      application have been defined. The analysis revealed that isolated microspores
      from maize display a classical heat-shock response characterized by the
      repression of the normal protein synthesis and the expression of a set of HSPs. A
      high complexity of the response was demonstrated, with numerous different HSPs
      being resolved in each known major HSP molecular weight class. However, the
      extent of this heat-shock response is limited in that some of these HSPs do not
      accumulate at high levels following temperature elevation. Comparative analysis
      of the heat-shock responses of microspores isolated from five genotypes
      demonstrated high levels of genetic variability. Furthermore, many HSPs were
      detected in microspores at control temperature, indicating a possible involvement
      of these proteins in pollen development at stages close to first pollen mitosis.

PMID- 12226350
TI  - The Effect of Nitrogen Nutrition on the Cellular Localization of Glutamine
      Synthetase Isoforms in Barley Roots.
AB  - Glutamine synthetase (GS) was detected by immunogold localization in the cytosol
      and plastids of roots of 7-d-old barley (Hordeum vulgare L. cv Klaxon) seedlings
      grown in the presence or absence of NO3- (15 mM) or NH4+ (30 mM). The number of
      GS polypeptides changed during root development, and this was affected by N
      nutrition. There was no evidence of a NO3--inducible root plastid GS.In apical 5-
      to 10-mm regions of the root the concentration of immunogold labeling of
      cytosolic GS was higher in the cortical parenchyma than in the vascular cells of
      the stele, irrespective of N nutrition. This labeling was at least 50% higher in
      both cell types in N-free compared with N-grown (either NO3- or NH4+) seedlings.
      In contrast, GS specific activity was highest in roots of NO3--grown seedlings.
      It is suggested that this indicates the presence of inactive GS in roots grown
      without N. This study has identified both cell- and development-specific
      responses of GS to N nutrition.

PMID- 12226351
TI  - Roots of Iron-Efficient Maize also Absorb Phytosiderophore-Chelated Zinc.
AB  - To investigate the recognition of Zn-phytosiderophores by the putative Fe
      phytosiderophore transporter in maize (Zea mays L.) roots, short-term uptake of
      65Zn-labeled phytosiderophores was compared in the Fe-efficient maize cultivar
      Alice and the maize mutant ys1 carrying a defect in Fe-phytosiderophore uptake.
      In ys1, uptake and translocation rates of Zn from Zn-phytosiderophores were one
      half of those in Alice, but no genotypical difference was found in Zn uptake and
      translocation from other Zn-binding forms. In ys1 and in tendency also in Alice,
      Zn uptake decreased with increasing stability constant of the chelate in the
      order: ZnSO4 [greater than or equal to] Zn-desferrioxamine > Zn-phytosiderophores
      > Zn-EDTA. Adding a 500-fold excess of free phytosiderophores over Zn to the
      uptake solution depressed Zn uptake in ys1 almost completely. In uptake studies
      with double-labeled 65Zn-14C-phytosiderophores, ys1 absorbed the phytosiderophore
      at similar rates when supplied as a Zn-chelate or the free ligand. By contrast,
      in Alice 14C-phytosiderophore uptake from the Zn-chelate was 2.8-fold higher than
      from the free ligand, suggesting that Alice absorbed the complete Zn
      phytosiderophore complex via the putative plasma membrane transporter for Fe
      phytosiderophores. We propose two pathways for the uptake of Zn from Zn
      phytosiderophores in grasses, one via the transport of the free Zn cation and the
      other via the uptake of nondissociated Zn-phytosiderophores.

PMID- 12226352
TI  - Rapid Germination of a Barley Mutant Is Correlated with a Rapid Turnover of
      Abscisic Acid Outside the Embryo.
AB  - In our study of the role of abscisic acid (ABA) in controlling the germination of
      barley grains, we tested a barley mutant line with a gigantum appearance (Hordeum
      distichum cv Quantum) for an ABA-insensitive phenotype by assaying germination in
      the presence of 10-4 M ABA. Dissected embryos of the mutant germinated at least
      10 h earlier than did those of the wild type. The half-maximal concentrations of
      ABA inhibitory for germination were determined to be 5 x 10-4 M for the mutant
      and 10-6 M for the wild type. Expression of an ABA-induced Rab gene was studied
      to determine ABA responsiveness. The ABA concentration required for a half
      maximal induction of Rab gene expression was 4 x 10-6 M in isolated embryos of
      both the mutant and wild type. This result suggests that ABA signal transduction
      pathways were not affected in the mutant. When isolated embryos were allowed to
      imbibe in water, ABA was released from the mutant and wild-type embryos at the
      same rate. However, the free ABA level in the incubation medium of the mutant
      showed a much faster decrease than that of the wild type, as demonstrated by two
      independent ABA assay methods (high-performance liquid chromatography and enzyme
      linked immunosorbent assay). Our results suggest that turnover of ABA outside the
      embryo is a determining factor in the germination of barley seeds.

PMID- 12226353
TI  - Characterization of Glutathione Uptake in Broad Bean Leaf Protoplasts.
AB  - Transport of reduced glutathione (GSH) and oxidized glutathione (GSSG) was
      studied with broad bean (Vicia faba L.) leaf tissues and protoplasts. Protoplasts
      and leaf discs took up GSSG at a rate about twice the uptake rate of GSH.
      Detailed studies with protoplasts indicated that GSH and GSSG uptake exhibited
      the same sensitivity to the external pH and to various chemical reagents. GSH
      uptake was inhibited by GSSG and glutathione conjugates. GSSG uptake was
      inhibited by GSH and GS conjugates, and the uptake of metolachlor-GS was
      inhibited by GSSG. Various amino acids (L-glutamic acid, L-glutamine, L-cysteine,
      L-glycine, L-methionine) and peptides (glycine-glycine, glycine-glycine-glycine)
      affected neither the transport of GSH nor GSSG. Uptake kinetics indicate that GSH
      is taken up by a single saturable transporter, with an apparent Km of 0.4 mM,
      whereas GSSG uptake exhibits two saturable phases, with an apparent Km of 7 [mu]M
      and 3.7 mM. It is concluded that the plasma membrane of leaf cells contains a
      specific transport system for glutathione, which takes up GSSG and GS conjugates
      preferentially over GSH. Proton flux measurements and electrophysiological
      measurements indicate that GSH and GSSG are taken up with proton symport.
      However, a detailed analysis of these measurements suggests that the ion
      movements induced by GSSG differ from those induced by GSH.

PMID- 12226354
TI  - Hydroxycinnamoyltransferases Involved in the Accumulation of Caffeic Acid Esters
      in Gametophytes and Sporophytes of Equisetum arvense.
AB  - Four hydroxycinnamoyltransferases from Equisetum arvense L. were studied that
      catalyze the formation of mono-O-caffeoyl-meso-tartrate, di-O-caffeoyl-meso
      tartrate, 5-O-caffeoylshikimate (dactylifrate), and 5-O-caffeoylquinate
      (chlorogenate). The enzymes were classified as coenzyme A (CoA)-ester-dependent
      acyltransferases (EC 2.3.1), i.e. hydroxycinnamoyl-CoA:meso-tartrate
      hydroxycinnamoyltransferase (CTT), hydroxycinnamoyl-CoA:caf-feoyl-meso-tartrate
      hydroxycinnamoyltransferase (CCT), hydroxycinnamoyl-CoA:shikimate
      hydroxycinnamoyltransferase (CST), and hydroxycinnamoyl-CoA:quinate
      hydroxycinnamoyltransferase. The CTT, CCT, and CST were partially purified and
      separated from E. arvense gametophytes by hydrophobic interaction chromatography
      on Fractogel TSK Butyl-650 followed by molecular exclusion on fast protein liquid
      chromatography-Superdex-75 with 87-, 62-, and 130- fold enrichments and 12, 8,
      and 11% yields, respectively. The enzyme activities obtained with caffeoyl-CoA
      were 95 (CTT), 74 (CCT), and 200 [mu]kat (CST) kg-1 protein. The apparent native
      relative molecular weight values were found to be approximately 45,000 (CTT),
      52,000 (CCT), and 50,000 (CST). Each enzyme showed highest activities at pH 7.5,
      the CCT and CST in Tris-HCl (1.2 and 1.0 M) and the CTT in imidazole-HCl (1.25
      M). Enzyme activities were stimulated more than 3-fold by 100 mM ascorbate. The
      apparent energies of activation (kilojoules mol-1) were calculated to be 56
      (CTT), 69 (CST), and 76 (CCT). The enzymes accepted cinnamoyl-CoA and various
      hydroxycinnamoyl-CoAs. The time course of the transferase activities along with
      that of a fourth one, hydroxycinnamoyl-CoA:quinate hydroxycinnamoyltransferase,
      and the pattern of product accumulation were determined during a 1-year growth
      period of the E. arvense sporophytes.

PMID- 12226355
TI  - Water-Deficit Tolerance and Field Performance of Transgenic Alfalfa
      Overexpressing Superoxide Dismutase.
AB  - Transgenic alfalfa (Medicago sativa) expressing Mn-superoxide dismutase cDNA
      tended to have reduced injury from water-deficit stress as determined by
      chlorophyll fluorescence, electrolyte leakage, and regrowth from crowns. A 3-year
      field trial indicated that yield and survival of transgenic plants were
      significantly improved, supporting the hypothesis that tolerance of oxidative
      stress is important in adaptation to field environments.

PMID- 12226356
TI  - Plasma Membrane Na+ Transport in a Salt-Tolerant Charophyte (Isotopic Fluxes,
      Electrophysiology, and Thermodynamics in Plants Adapted to Saltwater and
      Freshwater).
AB  - In salt-tolerant Chara longifolia, enhanced Na+ efflux plays an important role in
      maintaining low cytoplasmic Na+. When it is cultured in fresh water (FW), C.
      longifolia has a higher Na+ efflux than the obligate FW Chara corallina, although
      pH dependence and inhibitor profiles are similar for both species (J. Whittington
      and M.A. Bisson [1994] J Exp Bot 45: 657-665). When it is cultured in saltwater,
      C. longifolia has a Na+ efflux of 264 [plus or minus] 14 nmol m-2 s-1 at pH 7, 13
      times higher than FW-adapted cultures and 31 times higher than C. corallina. As
      in FW-adapted plants, efflux is highest at pH 5, but pH dependence is less steep
      and more linear in cells adapted to saltwater. In plants of both species from FW
      cultures, Na+ efflux is inhibited by Li+ at pH 5 but not at pH 7 or 9, whereas in
      the salt-adapted C. longifolia, Li+ inhibits Na+ efflux at pH 7 and 9 but not at
      pH 5. Amiloride inhibits Na+ efflux in salt-adapted cells but not in FW cells. We
      conclude that a new type of Na+ efflux system is induced in salt-adapted plants,
      although both systems have characteristics suggestive of a Na+/H+ antiport. In
      all cases, a 1:1 Na+/H+ antiport would have sufficient energy to maintain the
      cytoplasmic Na+ activities measured at pH 5 and 7 but not at pH 9, which suggests
      that another efflux system must be operating at pH 9.

PMID- 12226357
TI  - Role of the Plasma Membrane H+-ATPase in K+ Transport.
AB  - The role of the plant plasma membrane H+-ATPase in K+ uptake was examined using
      red beet (Beta vulgaris L.) plasma membrane vesicles and a partially purified
      preparation of the red beet plasma membrane H+-ATPase reconstituted in
      proteoliposomes and planar bilayers. For plasma membrane vesicles, ATP-dependent
      K+ efflux was only partially inhibited by 100 [mu]M vanadate or 10 [mu]M carbonyl
      cyanide-p-trifluoromethoxyphenylhydrazone. However, full inhibition of ATP
      dependent K+ efflux by these reagents occurred when the red beet plasma membrane
      H+-ATPase was partially purified and reconstituted in proteoliposomes. When
      reconstituted in a planar bilayer membrane, the current/voltage relationship for
      the plasma membrane H+-ATPase showed little effect of K+ gradients imposed across
      the bilayer membrane. When taken together, the results of this study demonstrate
      that the plant plasma membrane H+-ATPase does not mediate direct K+ transport
      chemically linked to ATP hydrolysis. Rather, this enzyme provides a driving force
      for cellular K+ uptake by secondary mechanisms, such as K+ channels or H+/K+
      symporters. Although the presence of a small, protonophore-insensitive component
      of ATP-dependent K+ transport in a plasma membrane fraction might be mediated by
      an ATP-activated K+ channel, the possibility of direct K+ transport by other
      ATPases (i.e. K+-ATPases) associated with either the plasma membrane or other
      cellular membranes cannot be ruled out.

PMID- 12226358
TI  - Autophagy in Tobacco Suspension-Cultured Cells in Response to Sucrose Starvation.
AB  - The response of tobacco (Nicotiana tabacum) suspension-cultured cells (BY-2) to
      nutrient starvation was investigated. When the cells that were grown in Murashige
      Skoog medium containing 3% (w/v) sucrose were transferred to the same medium
      without sucrose, 30 to 45% of the intracellular proteins were degraded in 2 d. An
      analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed
      that proteins were degraded nonselectively. With the same treatment, protease
      activity in the cell, which was measured at pH 5.0 using fluorescein
      thiocarbamoyl-casein as a substrate, increased 3- to 7-fold after 1 d. When the
      cysteine protease inhibitor (2S,3S)-trans-epoxysuccinyl-L-leucylamido-3-methyl
      butane (10 [mu]M) was present in the starvation medium, both the protein
      degradation and the increase in the protease activity were effectively inhibited.
      Light microscopy analysis showed that many small spherical bodies accumulated in
      the perinuclear region of the cytosol 8 h after the start of the inhibitor
      treatment. These bodies were shown to be membrane-bound vesicles of 1 to 6 [mu]m
      in diameter that contained several particles. Quinacrine stained these vesicles
      and the central vacuole; thus, both organelles are acidic compartments.
      Cytochemical enzyme analysis using 1-naphthylphosphate and [beta]
      glycerophosphate as substrates showed that these vesicles contained an acid
      phosphatase(s). We suggest that these vesicles contribute to cellular protein
      degradation stimulated under sucrose starvation conditions.

PMID- 12226359
TI  - Competence for Regeneration during Tobacco Internodal Development (Involvement of
      Plant Age, Cell Elongation Stage, and Degree of Polysomaty).
AB  - This study deals with internodal development in vegetative plants of Nicotiana
      tabacum cv Samsun NN and its reflection in changes of the cellular competence for
      regeneration. During elongation of the internodes, the cells of the epidermis,
      subepidermis, and cortex exclusively expanded and increased their DNA content
      cell type specifically, generally from 2C to 4C. Cells with the 8C DNA content
      were found mainly among the cortex cells of mature internodes. The frequency of
      shoot regeneration (directly from subepidermal and epidermal cells together) on
      thin cell layer explants increased to an optimum along with elongation of the
      internodes and decreased in mature internodes along with aging. The frequencies
      of diploid shoots among the regenerants from elongating and mature internodes
      were high (88 and 75% on the average, respectively), indicating that most cells
      that had achieved the 4C DNA content generally retained the G2 phase of the
      diploid cell cycle. Shoots regenerated from explants of young plant material
      mainly had a vitrified appearance. The occurrence of this type of malformed
      growth was already determined by the physiological state of the cells in the
      internode and did not interfere with their acquisition of competence.
      Vitrification was unrelated to the degree of polysomaty of the internodal tissue.
      Using the occurrence of tetraploid root regenerants (from intermediate cortex
      derived callus), up to a frequency of 50%, we show that the position in the plant
      where a majority of the 4C cortex cells switched to the G1 phase of the
      tetraploid cell cycle was at the transition from the elongation phase to the
      mature phase.

PMID- 12226360
TI  - Evidence for an Elongation/Reduction/C1-Elimination Pathway in the Biosynthesis
      of n-Heptane in Xylem of Jeffrey Pine.
AB  - The biosynthetic pathway to n-heptane was investigated by examining the effect of
      the [beta]-keto acyl-acyl carrier protein synthase inhibitor (2R,3S)-2,3-epoxy-4
      oxo-7E,10E-dodecadienamide (cerulenin), a thiol reagent ([beta]-mercaptoethanol),
      and an aldehydetrapping reagent (hydroxylamine) on the biosynthesis of n
      [14C]heptane and putative intermediates in xylem sections of Jeffrey pine (Pinus
      jeffreyi Grev.& Balf.) incubated with [14C]acetate. Cerulenin inhibited C18 fatty
      acid biosynthesis but had relatively little effect on radiolabel incorporation
      into C8 fatty acyl groups and n-heptane. [beta]-Mercaptoethanol inhibited n
      heptane biosynthesis, with a corresponding accumulation of radiolabel into both
      octanal and 1-octanol, whereas hydroxylamine inhibited both n-heptane and 1
      octanol biosynthesis, with radiolabel accumulation in octyl oximes. [14C]Octanal
      was converted to both n-heptane and 1-octanol when incubated with xylem sections,
      whereas [14C]1-octanol was converted to octanal and n-heptane in a hydroxylamine
      sensitive reaction. These results suggest a pathway for the biosynthesis of n
      heptane whereby acetate is polymerized via a typical fatty acid synthase reaction
      sequence to yield a C8 thioester, which subsequently undergoes a two-electron
      reduction to generate a free thiol and octanal, the latter of which alternately
      undergoes an additional, reversible reduction to form 1-octanol or loss of C1 to
      generate n-heptane.

PMID- 12226361
TI  - Membrane-Delimited Phosphorylation Enables the Activation of the Outward
      Rectifying K Channels in Motor Cell Protoplasts of Samanea saman.
AB  - Outward-rectifying K channels activated by membrane depolarization (Kout or KD
      channels) control K+ efflux from plant cells. To find out to what extent
      phosphorylation is required for the activity of these channels, the patch-clamp
      method was applied to protoplasts from the legume Samanea saman in both whole
      cell and isolated-patch configurations. In the absence of either Mg2+ or ATP in
      the "cytosolic" solution, the KD channel activity declined completely within 15
      min. This decline could be reversed in excised, inside-out patches by restoring
      MgATP (1 mM) to the cytoplasmic side of the membrane. Mg2+ (1 mM) plus 5[prime]
      adenylylimidodiphosphate (1 mM), a nonhydrolyzable ATP analog, did not substitute
      for ATP. Mg2+ (1 mM) plus adenosine 5[prime]-O-(3-thiotriphosphate) (25 to <100
      [mu]M), an irreversibly thiophosphorylating ATP analog, sustained channel
      activity irreversibly. 1-(5-IsoquinolinesulphonyI)-2- methylpiperazine (100
      [mu]M), a broad-range kinase inhibitor, blocked the activity of KD channels in
      the presence of MgATP. These results strongly suggest that the activation of the
      outward-rectifying K channels by depolarization depends critically on
      phosphorylation by a kinase tightly associated with the KD channel.

PMID- 12226362
TI  - Predicting Light Acclimation in Cyanobacteria from Nonphotochemical Quenching of
      Photosystem II Fluorescence, Which Reflects State Transitions in These Organisms.
AB  - An important factor in photosynthetic ecophysiology is the light regime that a
      photobiont is acclimated to exploit. In a wide range of cyanobacteria and cyano
      lichens, the easily measured fluorescence parameters, coefficient of
      nonphotochemical quenching of photosystem II variable fluorescence (qN) and
      nonphotochemical quenching, decline to a minimum near the acclimated growth light
      intensity. This characteristic pattern predicts the integrated light regime to
      which populations are acclimated, information that is particularly useful for
      cyanobacteria or cyano-lichens from habitats with highly variable light
      intensities. qN reflects processes that compete with photosystem II
      photochemistry for absorbed excitation energy. In cyanobacteria, we find no
      evidence for energy-dependent quenching mechanisms, which are the predominant
      components of qN in higher plants. Instead, in cyanobacteria, qN correlates
      closely with the excitation flow from the phycobilisome to photosystem I,
      indicating that qN reflects the state transition mechanism for equilibration of
      excitation from the phycobilisome to the two photosystems.

PMID- 12226364
TI  - Differential Expression of Two Endo-1,4-[beta]-Glucanase Genes in Pericarp and
      Locules of Wild-Type and Mutant Tomato Fruit.
AB  - The mRNA accumulation of two endo-1,4-[beta]-D-glucanase genes, Cel1 and Cel2,
      was examined in the pericarp and locules throughout the development of normal
      tomato (Lycopersicon esculentum) fruit and the ripening-impaired mutants rin and
      Nr. Both Cel1 and Cel2 were expressed transiently at the earliest stages of fruit
      development during a period corresponding to cell division and early cell
      expansion. In the pericarp, the mRNA abundance of both genes increased markedly
      at the breaker stage; the level of Cel1 mRNA decreased later in ripening, and
      that of Cel2 increased progressively. Cel2 mRNA levels also increased at the
      breaker stage in locules but after initial locule liquefaction was already
      complete. In rin fruit mRNA abundance of Cel1 was reduced and Cel2 was virtually
      absent, whereas in Nr Cel1 was expressed at wild-type levels and Cel2 was
      reduced. In wild-type fruit ethylene treatment slightly promoted the mRNA
      accumulation of both genes. In rin fruit ethylene treatment strongly increased
      the mRNA abundance of Cel1 to an extent greater than in wild-type fruit, but Cel2
      mRNA was absent even after ethylene treatment. These two endo-1,4-[beta]-D
      glucanase genes, therefore, do not show coordinated expression during fruit
      development and are subject to distinct regulatory control. These results suggest
      that the product of the Cel2 gene contributes to ripening-associated cell-wall
      changes.

PMID- 12226365
TI  - Analysis of the Import of Carboxyl-Terminal Truncations of the 23-Kilodalton
      Subunit of the Oxygen-Evolving Complex Suggests That Its Structure Is an
      Important Determinant for Thylakoid Transport.
AB  - A series of deletions from the carboxyl terminus of the 23-kD subunit of the
      photosynthetic oxygen-evolving complex OE23 revealed that these truncations
      result in various degrees of inhibition of translocation across thylakoid
      membranes and their subsequent assembly to the oxygen-evolving complex. Import of
      in vitro translated precursors across the chloroplast envelopes was not inhibited
      by these truncations. Time-course studies of the import of truncated OE23
      precursors into intact chloroplasts revealed that the stromal intermediate was
      subsequently translocated into the thylakoid lumen, where it was processed to a
      smaller size and rapidly degraded. In contrast to the full-length OE23
      intermediate, the truncated intermediate forms that accumulated in the stroma as
      a result of de-energization of thylakoid membranes could be found associated with
      the membrane rather than free in the stroma. Protease digestion experiments
      revealed that the deletions evidently altered the folded conformation of the
      protein. These results suggest that the carboxyl-terminal portion of the OE23
      precursor is important for the maintenance of an optimal structure for import
      into thylakoids, implying that the efficient translocation of OE23 requires the
      protein to be correctly folded. In addition, the rapid degradation of the
      truncated forms of the processed OE23 within the lumen indicates that a protease
      (or proteases) active in the lumen can recognize and remove misfolded
      polypeptides.

PMID- 12226366
TI  - Molecular and Structural Changes in Chlamydomonas under Limiting CO2 (A Possible
      Mitochondrial Role in Adaptation).
AB  - When Chlamydomonas reinhardtii cells are transferred to limiting CO2, one
      response is the induction of a CO2-concentrating mechanism (CCM) with components
      that remain to be identified. Characterization of membrane-associated proteins
      induced by this transfer revealed that synthesis of the 21-kD protein (LIP-21)
      was regulated at the level of translatable message abundance and correlated well
      with the induction of CCM activity. Phase partitioning of LIP-21 and the
      previously characterized LIP-36 showed that both appeared to be peripherally
      associated with membranes, which limits their potential to function as
      transporters of inorganic carbon. Ultrastructural changes that occur when cells
      are transferred to limiting CO2 were also examined to help form a model for the
      CCM or other aspects of adaptation to limiting CO2. Changes were observed in
      vacuolization, starch distribution, and mitochondrial location. The mitochondria
      relocated from within the cup of the chloroplast to between the chloroplast
      envelope and the plasma membrane. In addition, immunogold labeling demonstrated
      that LIP-21 was localized specifically to the peripheral mitochondria. These data
      suggest that mitochondria, although not previously incorporated into models for
      the CCM, may play an important role in the cell's adaptation to limiting CO2.

PMID- 12226367
TI  - Rapid [gamma]-Aminobutyric Acid Synthesis and the Inhibition of the Growth and
      Development of Oblique-Banded Leaf-Roller Larvae.
AB  - The hypothesis that rapid [gamma]-aminobutyrate (GABA) accumulation is a plant
      defense against phytophagous insects was investigated. Increasing GABA levels in
      a synthetic diet from 1.6 to 2.6 [mu]mol g-1 fresh weight reduced the growth
      rates, developmental rates, and survival rates of cultured Choristoneura
      rosaceana cv Harris larvae. Simulation of the mechanical damage resulting from
      phytophagous activity increased soybean (Glycine max L.) leaf GABA 10- to 25-fold
      within 1 to 4 min. Pulverizing leaf tissue resulted in a value of 2.15 ([plus or
      minus]0.11 SE) [mu]mol GABA g-1 fresh weight.

PMID- 12226368
TI  - Plant Physiology Has Become Plant Biology, A Cross-Disciplinary Science.

PMID- 12226369
TI  - Sizing Up the Floral Meristem.

PMID- 12226370
TI  - Genetic Analysis of Gibberellin Signal Transduction.

PMID- 12226371
TI  - Root Carbon Dioxide Fixation by Phosphorus-Deficient Lupinus albus (Contribution
      to Organic Acid Exudation by Proteoid Roots).
AB  - When white lupin (Lupinus albus L.) is subjected to P deficiency lateral root
      development is altered and densely clustered, tertiary lateral roots (proteoid
      roots) are initiated. These proteoid roots exude large amounts of citrate, which
      increases P solubilization. In the current study plants were grown with either 1
      mM P (+P-treated) or without P (-P-treated). Shoots or roots of intact plants
      from both P treatments were labeled independently with 14CO2 to compare the
      relative contribution of C fixed in each with the C exuded from roots as citrate
      and other organic acids. About 25-fold more acid-stable 14C, primarily in citrate
      and malate, was recovered in exudates from the roots of -P-treated plants
      compared with +P-treated plants. The rate of in vivo C fixation in roots was
      about 4-fold higher in -P-treated plants than in +P-treated plants. Evidence from
      labeling intact shoots or roots indicates that synthesis of citrate exuded by -P
      treated roots is directly related to nonphotosynthetic C fixation in roots. C
      fixed in roots of -P-treated plants contributed about 25 and 34% of the C exuded
      as citrate and malate, respectively. Nonphotosynthetic C fixation in white lupin
      roots is an integral component in the exudation of large amounts of citrate and
      malate, thus increasing the P available to the plant.

PMID- 12226372
TI  - Influence of Auxin and Gibberellin on in Vivo Protein Synthesis during Early Pea
      Fruit Growth.
AB  - Developing pea fruits (Pisum sativum L.) offer a unique opportunity to study
      growth and development in a tissue that is responsive to both gibberellins (GAs)
      and auxin (4-chloroindole-3-acetic acid[4-CI-IAA]). To begin a molecular analysis
      of the interaction of GAs and auxins in pea fruit development, in vivo labeling
      with [35S]methionine coupled with two-dimensional gel electrophoresis were used
      to characterize de novo synthesis of proteins during gibberellic acid (GA3)-, 4
      CI-indoleacetic acid-, and seed-induced pea pericarp growth. The most significant
      and reproducible polypeptide changes were observed between molecular weights of
      20 and 60. Comparing about 250 de novo synthesized proteins revealed that seed
      removal changed the pattern substantially. We identified one class of
      polypeptides that was uniquely seed induced and five classes that were affected
      by hormone treatment. The latter included 4-CI-IAA-induced, GA3-induced, GA3- and
      4-CI-IAA-induced, 4-CI-IAA-repressed, and GA3- and 4-CI-IAA-repressed
      polypeptides. Similar patterns of protein expression were associated with both
      hormone treatments; however, changes unique to GA3 or 4-CI-IAA treatment also
      indicate that the effects of GA3 and 4-CI-IAA on this process are not equivalent.
      In general, application of 4-CI-IAA plus GA3 replaced the seed effects on
      pericarp protein synthesis, supporting our hypothesis that both hormones are
      involved in pea pericarp development.

PMID- 12226373
TI  - The Gibberellin Status of lip1, a Mutant of Pea That Exhibits Light-Independent
      Photomorphogenesis.
AB  - Dark-grown seedlings of the lip1 (light independent photomorphogenesis) mutant of
      Pisum sativum L. display many features of de-etiolated growth and are similar in
      many respects to wild-type (WT) seedlings grown in the light. The involvement of
      gibberellins (GAs) with the mutant phenotype was examined by applying GA1 and
      GA20 to the mutant and WT, and by quantifying endogenous GA1, GA8, GA19, GA20,
      and GA29 levels in the two genotypes. These experiments were conducted in both
      the light and the dark. In neither environment could GA application restore
      elongation in the mutant to that in GA-treated WT plants. Quantification of GAs
      provided further evidence that the mutant phenotype is not attributable to a
      deficiency in endogenous GA1. However, dark-grown lip1 seedlings contained lower
      levels of GA19 and higher levels of GA20 than dark-grown WT plants, whereas in
      the light, the effect of the mutation on the ratio of GA19 to GA20 was reversed.
      Thus, there appears to be a complex interaction between the lip1 mutation, the
      light regime, and the step GA19 to GA20.

PMID- 12226374
TI  - Ammonia Flux between Oilseed Rape Plants and the Atmosphere in Response to
      Changes in Leaf Temperature, Light Intensity, and Air Humidity (Interactions with
      Leaf Conductance and Apoplastic NH4+ and H+ Concentrations).
AB  - NH3 exchange between oilseed rape (Brassica napus) plants and the atmosphere was
      examined at realistic ambient NH3 levels under controlled environmental
      conditions. Different leaf conductances to NH3 diffusion were obtained by
      changing leaf temperature (10 to 40[deg]C), light intensity (0 to 600 [mu]mol m-2
      s-1), and air humidity (20 to 80%), respectively. NH3 adsorption to the cuticle
      with subsequent NH3 transport through the epidermis had no significant effect on
      the uptake of atmospheric NH3, even at 80% relative air humidity. NH3 fluxes
      increased linearly with leaf conductance when light intensities were increased
      from 0 to 600 [mu]mol m-2 s-1. Increasing leaf temperatures from 10 to 35[deg]C
      caused an exponential increase in NH3 emission from plants exposed to low ambient
      NH3 concentrations, indicating that leaf conductance was not the only factor
      responding to the temperature increase. The exponential relationship between NH3
      emission and temperature was closely matched by the temperature dependence of the
      mole fraction of gaseous NH3 above the leaf apoplast (NH3 compensation point), as
      calculated on the basis of NH4+ and H+ concentrations in the leaf apoplast at the
      different leaf temperatures. NH3 fumigation experiments showed that an increase
      in leaf temperature may cause a plant to switch from being a strong sink for
      atmospheric NH3 to being a significant NH3 source. In addition to leaf
      temperature, the size of the NH3 compensation point depended on plant N status
      and was related to plant ontogeny.

PMID- 12226375
TI  - Ubiquinone-1 Induces External Deamino-NADH Oxidation in Potato Tuber
      Mitochondria.
AB  - The addition of ubiquinone-1 (UQ-1) induced Ca2+-independent oxidation of deamino
      NADH and NADH by intact potato (Solanum tuberosum L. cv Bintje) tuber
      mitochondria. The induced oxidation was coupled to the generation of a membrane
      potential. Measurements of NAD+-malate dehydrogenase activity indicated that the
      permeability of the inner mitochondrial membrane to NADH and deamino-NADH was not
      altered by the addition of UQ-1. We conclude that UQ-1-induced external deamino
      NADH oxidation is due to a change in specificity of the external rotenone
      insensitive NADH dehydrogenase. The addition of UQ-1 also induced rotenone
      insensitive oxidation of deamino-NADH by inside-out submitochondrial particles,
      but whether this was due to a change in the specificity of the internal rotenone
      insensitive NAD(P)H dehydrogenase or to a bypass in complex I could not be
      determined.

PMID- 12226376
TI  - Ethoxyzolamide Differentially Inhibits CO2 Uptake and Na+-Independent and Na+
      Dependent HCO3- Uptake in the Cyanobacterium Synechococcus sp. UTEX 625.
AB  - The effects of ethoxyzolamide (EZ), a carbonic anhydrase inhibitor, on the active
      CO2 and Na+-independent and Na+-dependent HCO3- transport systems of the
      unicellular cyanobacterium Synechococcus sp. UTEX 625 were examined. Measurements
      of transport and accumulation using radiochemical, fluorometric, and mass
      spectrometric assays indicated that active CO2 transport and active Na+
      independent HCO3- transport were inhibited by EZ. However, Na+-independent HCO3-
      transport was about 1 order of magnitude more sensitive to EZ inhibition than was
      CO2 transport (50% inhibition = 12 [mu]M versus 80 [mu]M). The data suggest that
      both the active CO2 (G.D. Price, M.R. Badger [1989] Plant Physiol 89: 37-43) and
      the Na+ -independent HCO3 - transport systems possessed carbonic anhydrase-like
      activity as part of their mechanism of action. In contrast, Na+-dependent HCO3-
      transport was only partially (50% inhibition = 230 [mu]M) and noncompetitively
      inhibited by EZ. The collective evidence suggested that EZ inhibition of Na+ 
      dependent HCO3- transport was an indirect consequence of the action of EZ on the
      CO2 transport system, rather than a direct effect on HCO3- transport. A model is
      presented in which the core of the inorganic carbon translocating system is
      formed by Na+-dependent HCO3- transport and the CO2 transport system. It is
      argued that the Na+-independent HCO3 - utilizing system was not directly involved
      in translocation, but converted HCO3- to CO2 for use in CO2 transport.

PMID- 12226377
TI  - Salt-Sensitive Mutants of Chlamydomonas reinhardtii Isolated after Insertional
      Tagging.
AB  - We describe the isolation of salt-sensitive Chlamydomonas reinhardtii mutants by
      insertional mutagenesis using the nitrate reductase (Nit1) gene. The plasmid
      pMN24, containing Nit1, was used for transformation of 305CW15 (nit1 cw15 mt+),
      and transformants were selected for complementation of the nit- phenotype. From
      6875 nit+ colonies, four transformants (S4, S18, S46, and S66) were isolated that
      exhibited both Na+ and Li+ sensitivity (sod-), and another transformant (S33) was
      selected that exhibited sensitivity to Li+ but not Na+ (lit-) based on relative
      growth comparisons with the wild-type strain. S33, S46, and S66 were no more
      growth inhibited by sorbitol than was 305CW15. In comparison, S4 and S18
      exhibited substantial growth inhibition in medium supplemented with sorbitol.
      Genetic analyses indicated that the salt-sensitive mutants were each defective in
      a single recessive gene. The mutant genes in S4 (sod1), S33 (lit1), and S66
      (sod3) are linked to a functional copy of Nit1 and are presumably tagged with a
      pMN24 insertion.

PMID- 12226378
TI  - The Chlorophyll Biosynthetic Enzyme Mg-Protoporphyrin IX Monomethyl Ester
      (Oxidative) Cyclase (Characterization and Partial Purification from Chlamydomonas
      reinhardtii and Synechocystis sp. PCC 6803).
AB  - A universal structural feature of chlorophyll molecules is the isocyclic ring.
      This ring is formed by the action of the enzyme Mg-protoporphyrin IX monomethyl
      ester (oxidative) cyclase, which catalyzes a complex reaction in which Mg
      protoporphyrin IX monomethyl ester is converted to divinyl protochlorophyllide
      (also called Mg-2,4-divinylpheoporphyrin a5), with the participation of NADPH and
      O2. Cyclase activity was demonstrated in lysed Chlamydomonas reinhardtii
      chloroplasts and extracts of Synechocystis sp. PCC 6803. The yield of the
      reaction product was increased by the addition of catalase and ascorbate or
      isoascorbate to the incubation mixture. These compounds may act by preventing
      degradation of the tetrapyrroles by reactive oxygen species. Cyclase activity
      from C. reinhardtii was not inhibited by the flavoprotein inhibitor quinacrine or
      by the hemoprotein inhibitors CO, KCN, or NaN3. In contrast, cyclase activity in
      extracts of C. reinhardtii and Synechocystis sp. PCC 6803 was inhibited by
      chelators of Fe, suggesting that nonheme Fe is involved in the reaction. Cyclase
      in lysed C. reinhardtii chloroplasts was associated with the membranes, and
      attempts to further fractionate or solubilize the activity were unsuccessful. In
      contrast, cyclase in Synechocystis sp. PCC 6803 extracts could be separated into
      soluble and membrane components, both of which were required for reconstitution
      of activity. The membrane component retained activity after it was solubilized by
      the detergent n-octyl-[beta]-D-glucopyranoside in the presence of glycerol and
      Mg2+. The solubilized membrane component was purified further by dye-affinity and
      ion-exchange chromatography.

PMID- 12226379
TI  - Insect Control and Dosage Effects in Transgenic Canola Containing a Synthetic
      Bacillus thuringiensis cryIAc Gene.
AB  - Zygotic hypocotyls of canola (Brassica napus L.) cv Oscar, cv Westar, and the
      breeding line UGA188-20B were transformed with a truncated synthetic Bacillus
      thuringiensis insecticidal crystal protein gene (Bt cryIAc) under the control of
      the cauliflower mosaic virus 35S promoter using Agrobacterium tumefaciens
      mediated transformation. Fifty-seven independently transformed lines were
      produced, containing 1 to 12 copies of the transgenes. A range of cry expressors
      was produced from 0 to 0.4% Cry as a percentage of total extractable protein. The
      Brassica specialists, the diamondback month (Plutella xylostella L.) and the
      cabbage looper (Trichoplusia ni Hubner), were completely controlled by low-,
      medium-, and high-expressing lines. Whereas control of the generalist
      lepidopteran, the corn earworm (Helicoverpa zea Boddie), was nearly complete, the
      other generalist caterpillar tested, the beet armyworm (Spodoptera exigua
      Hubner), showed a dose response that had a negative association between
      defoliation and cry expression. These plants were produced as models for an
      ecological research assessment of the risk involved in the field release of
      naturalized transgenic plants harboring a gene (Bt) that confers higher relative
      fitness under herbivore-feeding pressure.

PMID- 12226380
TI  - Biphasic Temporal and Spatial Induction Patterns of Defense-Related mRNAs and
      Proteins in Fungus-Infected Parsley Leaves.
AB  - Previous experiments using in situ RNA hybridization have shown that the mRNAs
      encoding phenylalanine ammonia-lyase, 4-coumarate:coenzyme A ligase, and
      pathogenesis-related protein 1 accumulated transiently around fungal infection
      sites in parsley (Petroselinum crispum) leaf buds. These studies have now been
      extended by (a) analyzing different stages of the infection process and (b)
      monitoring the timing of appearance and the spatial distribution of the proteins
      as well as the corresponding mRNAs. An early and short period of mRNA induction
      throughout a large portion of the infected leaf was followed by a longer period,
      during which the mRNA levels remained high in a more localized area around the
      site of fungal penetration with sharp borders toward the surrounding tissue. This
      biphasic pattern of mRNA accumulation was followed after some delay by the same
      pattern of protein accumulation.

PMID- 12226381
TI  - Analysis of Cytokinin Metabolism in ipt Transgenic Tobacco by Liquid
      Chromatography-Tandem Mass Spectrometry.
AB  - The endogenous levels of the major, naturally occurring cytokinins in Pisum
      sativum ribulose-1,5-bisphosphate carboxylase small subunit promoter-isopentenyl
      transferase gene (Pssu-ipt)-transformed tobacco (Nicotiana tabacum L.) callus
      were quantified using electrospray-liquid chromatography-tandem mass spectrometry
      during a 6-week subcultivation period. An ipt gene was expressed under control of
      a tetracycline-inducible promoter for a more detailed study of cytokinin
      accumulation and metabolism. Activation of the ipt in both expression systems
      resulted in the production of mainly zeatin-type cytokinins. No accumulation of
      isopentenyladenine or isopentenyladenosine was observed. In Pssu-ipt-transformed
      calli, as well as in the tetracycline-inducible ipt leaves, metabolic
      inactivation occurred through O-glucoside conjugation. No significant elevation
      of cytokinin N-glucosides levels was observed. Side-chain reduction to
      dihydrozeatin-type cytokinins was observed in both systems. The levels of the
      endogenous cytokinins varied in time and were subject to homeostatic regulatory
      mechanisms. Feeding experiments of ipt transgenic callus with
      [3H]isopentenyladenine and [3H]isopentenyladenosine mainly led to labeled adenine
      like compounds, which are degradation products from cytokininoxidase activity.
      Incorporation of radioactivity in zeatin riboside was observed, although to a
      much lesser extent.

PMID- 12226382
TI  - Solar Ultraviolet-B Radiation Affects Seedling Emergence, DNA Integrity, Plant
      Morphology, Growth Rate, and Attractiveness to Herbivore Insects in Datura ferox.
AB  - To study functional relationships between the effects of solar ultraviolet-B
      radiation (UV-B) on different aspects of the physiology of a wild plant, we
      carried out exclusion experiments in the field with the summer annual Datura
      ferox L. Solar UV-B incident over Buenos Aires reduced daytime seedling
      emergence, inhibited stem elongation and leaf expansion, and tended to reduce
      biomass accumulation during early growth. However, UV-B had no effect on
      calculated net assimilation rate. Using a monoclonal antibody specific to the
      cyclobutane-pyrimidine dimer (CPD), we found that plants receiving full sunlight
      had more CPDs per unit of DNA than plants shielded from solar UV-B, but the
      positive correlation between UV-B and CPD burden tended to level off at high
      (near solar) UV-B levels. At our field site, Datura plants were consumed by leaf
      beetles (Coleoptera), and the proportion of plants attacked by insects declined
      with the amount of UV-B received during growth. Field experiments showed that
      plant exposure to solar UV-B reduced the likelihood of leaf beetle attack by one
      half. Our results highlight the complexities associated with scaling plant
      responses to solar UV-B, because they show: (a) a lack of correspondence between
      UV-B effects on net assimilation rate and whole-plant growth rate, (b) nonlinear
      UV-B dose-response curves, and (c) UV-B effects of plant attractiveness to
      natural herbivores.

PMID- 12226383
TI  - Light-Dependent Isoprene Emission (Characterization of a Thylakoid-Bound Isoprene
      Synthase in Salix discolor Chloroplasts).
AB  - Isoprene synthase is an enzyme that is responsible for the production of the
      volatile C5 hydrocarbon, isoprene, in plant leaves. Isoprene formation in
      numerous C3 plants is interesting because (a) large quantities of isoprene are
      emitted, 5 x 1014 g of C annually, (b) a plant may release 1 to 8% of its fixed C
      as isoprene, and (c) the function of plant isoprene production is unknown.
      Because of the dependence of foliar isoprene emission on light, the existence of
      a plastidic isoprene synthase has been postulated. To pursue this idea, a method
      to isolate chloroplasts from Salix discolor was developed and shows a plastidic
      isoprene synthase that is tightly bound to the thylakoid membrane and accessible
      to trypsin inactivation. The thylakoid-bound isoprene synthase has catalytic
      properties similar to known soluble isoprene synthases; however, the relationship
      between these enzymes is unknown. The discovery of a thylakoid-bound isoprene
      synthase with a stromal-facing domain places it in the chloroplast, where it may
      be subject to numerous direct and indirect light-mediated effects. Implications
      for the light-dependent regulation of foliar isoprene production and its function
      are presented.

PMID- 12226384
TI  - Role of Jasmonates in the Elicitor- and Wound-Inducible Expression of Defense
      Genes in Parsley and Transgenic Tobacco.
AB  - Jasmonates have been proposed to be signaling intermediates in the wound and/or
      elicitor-activated expression of plant defense genes. We used parsley
      (Petroselinum crispum) cell cultures and transgenic tobacco (Nicotiana tabacum)
      plants expressing 4CL1-GUS gene fusions to investigate the potential role played
      by jasmonates in mediating the wound and/or elicitor activation of
      phenylpropanoid and other defense-related genes. Jasmonates and [alpha]-linolenic
      acid strongly induced the expression of 4CL in a dose-dependent manner in parsley
      cells; methyl jasmonate also activated the coordinate expression of other
      phenylpropanoid genes and the accumulation of furanocoumarin phytoalexins.
      However, the response of the cells to optimal methyl jasmonate concentrations was
      distinct quantitatively and qualitatively from the response of elicitor-treated
      cells. In transgenic tobacco wound-inducible tobacco 4CL genes and a 4CL1
      promoter-GUS transgene were responsive to jasmonates and [alpha]-linolenic acid
      in a dose-dependent manner. Pre-treatment of parsley cells or tobacco leaves with
      a lipoxygenase inhibitor reduced their responsiveness to the elicitor and to
      wounding. These results show that the elicitor response in parsley cells can be
      partially mimicked by jasmonate treatment, which supports a role for jasmonates
      in mediating wound-induced expression of 4CL and other phenylpropanoid genes.

PMID- 12226386
TI  - Ethylene Biosynthesis and Accumulation under Drained and Submerged Conditions (A
      Comparative Study of Two Rumex Species).
AB  - A model is presented of the regulation of ethylene biosynthesis in relation to
      submergence and flooding resistance. It is based on time-course measurements of
      ethylene production, ethylene accumulation, and concentrations of free and
      conjugated 1-aminocyclo-propane-1-carboxylic acid (ACC) in submerged and drained
      flooding-resistant Rumex palustris Sm. and flooding-sensitive Rumex acetosella L.
      plants. From these data, in vivo reaction rates of the final steps in the
      ethylene biosynthetic pathway were calculated. According to our model,
      submergence stimulates ACC formation and inhibits conversion of ACC to ethylene
      in both Rumex species, and as a result, ACC accumulates. This may explain the
      stimulated ACC conjugation observed in submerged plants. Although submergence
      inhibited ethylene production, physical entrapment increased endogenous ethylene
      concentrations in both flooding-resistant R. palustris and flooding-sensitive R.
      acetosella plants. However, R. palustris plants controlled their internal
      ethylene levels in the long term by a negative regulation of ACC synthase induced
      by ethylene. In flooding-sensitive R. acetosella plants, absence of negative
      regulation increased internal ethylene levels to more than 20 [mu]L L-1 after 6 d
      of submergence. This may accelerate the process of senescence and contribute to
      their low level of flooding resistance.

PMID- 12226385
TI  - Aluminum Tolerance Acquired during Phosphate Starvation in Cultured Tobacco
      Cells.
AB  - Al toxicity in cultured tobacco cells (Nicotiana tabacum L. cv Samsun;
      nonchlorophyllic cell line SL) has been investigated in nutrient medium. In this
      system, Al and Fe(II) (ferrous ion) in the medium synergistically result in the
      accumulation of both Al and Fe, the peroxidation of lipids, and eventually death
      in cells at the logarithmic phase of growth (+P cells). A lipophilic antioxidant,
      N,N[prime]-diphenyl-p-phenylenediamine, protected +P cells from the peroxidation
      of lipids and from cell death, suggesting that a relationship exists between the
      two. Compared with +P cells, cells that had been starved of Pi (-P cells) were
      more tolerant to Al, accumulated 30 to 40% less Al and 70 to 90% less Fe, and did
      not show any evidence of the peroxidation of lipids during Al treatment. These
      results suggest that -P cells exhibit Al tolerance because their plasma membranes
      are protected from the peroxidation of lipids caused by the combination of Al and
      Fe(II). It seems likely that the exclusion of Fe from -P cells might suppress
      directly Fe-mediated peroxidation of lipids. Furthermore, since -P cells
      accumulated [beta]-carotene, it is proposed that this carotenoid pigment might
      function as a radical-trapping antioxidant in the plasma membrane of cells
      starved of Pi.

PMID- 12226387
TI  - Stomatal Closure in Flooded Tomato Plants Involves Abscisic Acid and a Chemically
      Unidentified Anti-Transpirant in Xylem Sap.
AB  - We address the question of how soil flooding closes stomata of tomato
      (Lycopersicon esculentum Mill. cv Ailsa Craig) plants within a few hours in the
      absence of leaf water deficits. Three hypotheses to explain this were tested,
      namely that (a) flooding increases abscisic acid (ABA) export in xylem sap from
      roots, (b) flooding increases ABA synthesis and export from older to younger
      leaves, and (c) flooding promotes accumulation of ABA within foliage because of
      reduced export. Hypothesis a was rejected because delivery of ABA from flooded
      roots in xylem sap decreased. Hypothesis b was rejected because older leaves
      neither supplied younger leaves with ABA nor influenced their stomata. Limited
      support was obtained for hypothesis c. Heat girdling of petioles inhibited phloem
      export and mimicked flooding by decreasing export of [14C]sucrose, increasing
      bulk ABA, and closing stomata without leaf water deficits. However, in flooded
      plants bulk leaf ABA did not increase until after stomata began to close. Later,
      ABA declined, even though stomata remained closed. Commelina communis L.
      epidermal strip bioassays showed that xylem sap from roots of flooded tomato
      plants contained an unknown factor that promoted stomatal closure, but it was not
      ABA. This may be a root-sourced positive message that closes stomata in flooded
      tomato plants.

PMID- 12226388
TI  - NAD(P)H:(Quinone-Acceptor) Oxidoreductase of Tobacco Leaves Is a Flavin
      Mononucleotide-Containing Flavoenzyme.
AB  - The soluble NAD(P)H:(quinone-acceptor) oxidoreductase [NAD(P)H-QR, EC 1.6.99.2]
      of Nicotiana tabacum L. leaves and roots has been purified. NAD(P)H-QR contains
      noncovalently bound flavin mononucleotide. Pairs of subunits of 21.4 kD are
      linked together by disulfide bridges, but the active enzyme is a homotetramer of
      94 to 100 kD showing an isoelectric point of 5.1. NAD(P)H-QR is a B
      stereospecific dehydrogenase. NADH and NADPH are electron donors of similar
      efficiency with Kcat:Km ratios (with duroquinone) of 6.2 x 107 and 8.0 x 107 m-1
      s-1, respectively. Hydrophilic quinones are good electron acceptors, although
      ferricyanide and dichlorophenolindophenol are also reduced. The quinones are
      converted to hydroquinones by an obligatory two-electron transfer. No spectral
      evidence for a flavin semiquinone was detected following anaerobic
      photoreduction. Cibacron blue and 7-iodo-acridone-4-carboxylic acid are
      inhibitory. Tobacco NAD(P)H-QR resembles animal DT-diaphorase in some respects
      (identical reaction mechanism with a two-electron transfer to quinones, unusually
      high catalytic capability, and donor and acceptor substrate specificity), but it
      differs from DT-diaphorase in molecular structure, flavin cofactor,
      stereospecificity, and sensitivity to inhibitors. As in the case with DT
      diaphorase in animals, the main NAD(P)H-QR function in plant cells may be the
      reduction of quinones to quinols, which prevents the production of semiquinones
      and oxygen radicals. The enzyme appears to belong to a widespread group of plant
      and fungal flavoproteins found in different cell compartments that are able to
      reduce quinones.

PMID- 12226389
TI  - Regulation of De-N-Glycosylation Enzymes in Germinating Radish Seeds.
AB  - The activities of the de-N-glycosylation enzymes endo-N-acetyl- [beta]-D
      glucosaminidase (ENGase; EC 3.2.1.96) and peptide-N4- (N-acetyl-[beta]-D
      glucosaminyl) asparagine amidase (PNGase; EC 3.5.1.52) were monitored during
      germination and postgerminative development in radish (Raphanus sativus L. cv
      Flamboyant). The ENGase activity was detected only during postgermination,
      whereas the PNGase activity was present at high levels in both stages. When
      germination was inhibited with abscisic acid or cycloheximide, PNGase activity
      was detected at a basic level and ENGase activity was not detected at all. PNGase
      is present as an active protein in dry seeds and is apparently synthesized during
      seed formation. Conversely, the absence of ENGase in dry seeds suggests that its
      activity is dependent on the protein synthesis that occurs during and after
      germination. Treatment with gibberellic acid confirmed the production of both de
      N-glycosylation enzymes after germination, and demonstrated a temporal delay
      between the production of the two enzymes during this period. Our results suggest
      that the two de-N-glycosylation enzymes are differentially regulated during plant
      development.

PMID- 12226390
TI  - Evidence for the Contribution of the Mehler-Peroxidase Reaction in Dissipating
      Excess Electrons in Drought-Stressed Wheat.
AB  - Gross O2 evolution and uptake by attached, drought-stressed leaves of wheat
      (Triticum aestivum) were measured using a 16O2/ 18O2 isotope technique and mass
      spectrometry. The activity of photosystem II, determined from the rate of 16O2
      evolution, is only slightly affected under drought conditions. During drought
      stress, net CO2 uptake decreases due to stomatal closure, whereas the uptake of
      18O2 is stimulated. The main O2-consuming reactions in the light are the Mehler
      peroxidase (MP) reaction and the photorespiratory pathway. From measurements of
      the rate of carbon flux through the photorespiratory pathway, estimated by the
      analysis of the specific radioactivities of glycolate, we conclude that the rate
      of photorespiration is decreased with drought stress. Therefore, the O2 taken up
      in the light appears to be preferentially used by the MP reaction. In stressed
      leaves, 29.1% of the photosynthetic electrons are consumed in the MP reaction and
      18.4% drive the photorespiratory pathway. Thus, overreduction of the electron
      transport chain is avoided preferably by the MP reaction when drought stress
      restricts CO2 reduction.

PMID- 12226391
TI  - Nitrogen and Carbon Flows Estimated by 15N and 13C Pulse-Chase Labeling during
      Regrowth of Alfalfa.
AB  - The flow of 15N and 13C from storage compounds in organs remaining after
      defoliation (sources) to regrowing tissue (sinks), and 13C losses through root or
      shoot respiration were assessed by pulse-chase labeling during regrowth of
      alfalfa (Medicago sativa L.) following shoot removal. A total of 73% of labeled C
      and 34% of labeled N were mobilized in source organs within 30 d. Although all of
      the 15N from source organs was recovered in the regrowing tissue, much of the 13C
      was lost, mainly as CO2 respired from the root (61%) or shoot (8%), and was found
      to a lesser extent in sink tissue (5%). After 3, 10, or 30 d of regrowth, 87, 66,
      and 52% of shoot N, respectively, was derived from source tissue storage
      compounds; the rest resulted from translocation of fixed N2. Overall results
      suggest that most shoot C was linked to photosynthetic activity rather than being
      derived from mobilization of stored C in source organs. Furthermore, isotopic
      analysis of different chemical fractions of plant tissue suggests that between 14
      and 58% of the shoot C derived from source tissues was linked to the mobilization
      of N compounds, not carbohydrates.

PMID- 12226392
TI  - Syringolide 1 Triggers Ca2+ Influx, K+ Efflux, and Extracellular Alkalization in
      Soybean Cells Carrying the Disease-Resistance Gene Rpg4.
AB  - Alleles of avirulence gene D (avrD) specify the production by bacteria of
      syringolides that elicit the hypersensitive response in soybean (Glycine max)
      plants carrying the disease-resistance gene Rpg4, but not rpg4 plants.
      Syringolide 1 caused extracellular alkalization, K+ efflux, and Ca2+ influx about
      30 min after addition to suspension-cultured cells of two Rpg4 cultivars, Harosoy
      and Flambeau, but not in two rpg4 cultivars, Acme and Merit. All responses were
      sustained for at least 1.5 h and were inhibited by La3+, which blocks certain
      Ca2+ channels. These results suggest that syringolide 1 activates a Ca2+ influx
      dependent signaling pathway only in Rpg4 soybean cells.

PMID- 12226393
TI  - Dissection of the Blue-Light-Dependent Signal-Transduction Pathway Involved in
      Gametic Differentiation of Chlamydomonas reinhardtii.
AB  - Gametogenesis of the green alga Chlamydomonas reinhardtii may be viewed as a two
      step process that is controlled by the environmental cues of nitrogen deprivation
      and blue light. Initiation of gametogenesis is induced by nitrogen deprivation,
      resulting in mating-incompetent pregametes, when cells are kept in the dark. For
      the completion of gametic differentiation light is required. Pregametes were
      treated with pharmacological compounds to influence the light-dependent
      conversion to mature gametes. Dibutyryl-cyclic 3[prime]5[prime]
      adenosinemonophosphate, papaverine, and genistein were found to inhibit the
      progression of gametogenesis in the light. Treatment of pregametes in the dark
      with either staurosporine or papaverine resulted in their conversion to mature
      gametes. Apparently, papaverine has different effects in the dark and in the
      light; the effect of staurosporine suggested that a protein kinase C-like
      component inhibits the conversion of pregametes to gametes, a block that normally
      is relieved by illumination. This hypothesis was corroborated by the observation
      that activators of protein kinase C, N-heptyl-5-chloro-1-naphthalenesulfonamide,
      N- (6-phenylhexyl)-5-chloro-1-naphthalenesulfonamide, and the phorbolester
      phorbol-12-myristate 13-acetate inhibited gametogenesis in the light. Genistein
      and dibutyryl-cyclic 3[prime]5[prime] adenosinemonophosphate were able to inhibit
      the dark activation caused by staurosporine treatment, suggesting that their
      targets work downstream from the "protein kinase C-like" kinase. Surprisingly,
      staurosporine and papaverine worked synergystically on the activation of
      pregametes in the dark.

PMID- 12226394
TI  - Characterization of Novel Sesquiterpenoid Biosynthesis in Tobacco Expressing a
      Fungal Sesquiterpene Synthase.
AB  - The gene encoding trichodiene synthase (Tri5), a sesquiterpene synthase from the
      fungus Fusarium sporotrichioides, was used to transform tobacco (Nicotiana
      tabacum). Trichodiene was the sole sesquiterpene synthase product in enzyme
      reaction mixtures derived from unelicited transformant cell-suspension cultures,
      and both trichodiene and 5-epi-aristolochene were observed as reaction products
      following elicitor treatment. Immunoblot analysis of protein extracts revealed
      the presence of trichodiene synthase only in transformant cell lines producing
      trichodiene. In vivo labeling with [3H]mevalonate revealed the presence of a
      novel trichodiene metabolite, 15-hydroxytrichodiene, that accumulated in the
      transformant cell-suspension cultures. In a trichodiene-producing transformant,
      the level of 15-hydroxytrichodiene accumulation increased after elicitor
      treatment. In vivo labeling with [14C]acetate showed that the biosynthetic rate
      of trichodiene and 15-hydroxytrichodiene also increased after elicitor treatment.
      Incorporation of radioactivity from [14C]acetate into capsidiol was reduced
      following elicitor treatment of a trichodiene-producing transformant as compared
      with wild type. These results demonstrate that sesquiterpenoid accumulation
      resulting from the constitutive expression of a foreign sesquiterpene synthase is
      responsive to elicitation and that the farnesyl pyrophosphate present in elicited
      cells can be utilized by a foreign sesquiterpene synthase to produce high levels
      of novel sesquiterpenoids.

PMID- 12226395
TI  - Photosynthetic Gas Exchange and Discrimination against 13CO2 and C18O16O in
      Tobacco Plants Modified by an Antisense Construct to Have Low Chloroplastic
      Carbonic Anhydrase.
AB  - The physiological role of chloroplastic carbonic anhydrase (CA) was examined by
      antisense suppression of chloroplastic CA (on average 8% of wild type) in
      Nicotiana tabacum. Photosynthetic gas-exchange characteristics of low-CA and wild
      type plants were measured concurrently with short-term, on-line stable isotope
      discrimination at varying vapor pressure deficit (VPD) and light intensity. Low
      CA and wild-type plants were indistinguishable in the responses of assimilation,
      transpiration, stomatal conductance, and intercellular CO2 concentration to
      changing VPD or light intensity. At saturating light intensity, low-CA plants had
      lower discrimination against 13CO2 than wild-type plants by 1.2 to 1.8[per mille
      (thousand) sign]. Consequently, tissue of the low-CA plants was higher in 13C
      than the control plants. It was calculated that low-CA plants had chloroplast CO2
      concentrations 13 to 22 [mu]mol mol-1 lower than wild-type plants. Discrimination
      against C18O16O in low-CA plants was 20% of that of the wild type, confirming a
      role of chloroplastic CA in the mechanism of discrimination against C18O16O
      ([delta]C18O16O). As VPD increased, stomatal closure caused a reduction in
      chloroplastic C02 concentration, and since VPD and chloroplastic CO2
      concentration act in opposing directions on [delta]C18O16O, no effect of VPD was
      seen on [delta]C18O16O.

PMID- 12226396
TI  - NaCI Reduces Indole-3-Acetic Acid Levels in the Roots of Tomato Plants
      Independent of Stress-Induced Abscisic Acid.
AB  - Indole-3-acetic acid (IAA) was measured in leaves and roots of tomato
      (Lycopersicon esculentum) genotypes subjected to salt stress. An abscisic acid
      (ABA)-deficient mutant of tomato (sitiens), the genetic parent (Rheinlands Ruhm,
      RR), and a commercial variety (Large Cherry Red, LCR) of tomato were treated with
      50 to 300 mM NaCl in nutrient culture. Both LCR and RR had significantly higher
      levels of IAA in the roots compared with that in sitiens prior to treatment. The
      initial levels of IAA in the roots of LCR and RR declined by nearly 75% after
      exposure to NaCl, whereas those in roots from the sitiens mutant remained
      unchanged. IAA levels in the leaves of all genotypes remained unchanged or
      increased slightly in response to NaCl. ABA was highest in leaves from the normal
      genotypes after exposure to NaCl. ABA levels in the roots of sitiens were similar
      to the levels in the normal genotypes, whereas levels in the leaves were only 10%
      of the levels found in normal genotypes regardless of the salt treatment.
      Treatment of LCR and sitiens with exogenous ABA increased the ABA levels in
      leaves and roots, but there were no measurable changes in endogenous IAA.
      Therefore, the reduction in IAA appears to result from an ABA-independent effect
      of NaCl on IAA metabolism in the roots of stressed plants.

PMID- 12226397
TI  - Patterns of Carbon Partitioning in Leaves of Crassulacean Acid Metabolism Species
      during Deacidification.
AB  - Carbohydrates stored during deacidification in the light were examined in 11
      Crassulacean acid metabolism (CAM) species from widely separated taxa grown under
      uniform conditions. The hypothesis that NAD(P) malic enzyme CAM species store
      chloroplastic starch and glucans, and phosphoenolpyruvate carboxykinase species
      store extrachloroplastic sugars or polymers was disproved. Of the six malic
      enzyme species examined, Kalanchoe tubiflora, Kalanchoe pinnata, Kalanchoe
      daigremontiana, and Vanilla planifolia stored mainly starch. Sansevieria hahnii
      stored sucrose and Agave guadalajarana did not store starch, glucose, fructose,
      or sucrose. Of the five phosphoenolpyruvate carboxykinase species investigated,
      Ananus comosus stored extrachloroplastic carbohydrate, but Stapelia gigantea,
      Hoya carnosa, and Portea petropolitana stored starch, whereas Aloe vera stored
      both starch and glucose. Within families, the major decarboxylase was common for
      all species examined, whereas storage carbohydrate could differ both between and
      within genera. In the Bromeliaceae, A. comosus stored mainly fructose, but P.
      petropolitana stored starch. In the genus Aloe, A. vera stored starch and
      glucose, but A. arborescens is known to store a galactomannan polymer. We
      postulate that the observed variation in carbohydrate partitioning between CAM
      species is the result of two principal components: (a) constraints imposed by the
      CAM syndrome itself, and (b) diversity in biochemistry resulting from different
      evolutionary histories.

PMID- 12226398
TI  - Leaf Abscission Induced by Ethylene in Water-Stressed Intact Seedlings of
      Cleopatra Mandarin Requires Previous Abscisic Acid Accumulation in Roots.
AB  - The involvement of abscisic acid (ABA) in the process of leaf abscission induced
      by 1-aminocyclopropane-1-carboxylic acid (ACC) transported from roots to shoots
      in Cleopatra mandarin (Citrus reshni Hort. ex Tan.) seedlings grown under water
      stress was studied using norflurazon (NF). Water stress induced both ABA (24
      fold) and ACC (16-fold) accumulation in roots and arrested xylem flow. Leaf bulk
      ABA also increased (8-fold), although leaf abscission did not occur. Shortly
      after rehydration, root ABA and ACC returned to their prestress levels, whereas
      sharp and transitory increases of ACC (17-fold) and ethylene (10-fold) in leaves
      and high percentages of abscission (up to 47%) were observed. NF suppressed the
      ABA and ACC accumulation induced by water stress in roots and the sharp increases
      of ACC and ethylene observed after rewatering in leaves. NF also reduced leaf
      abscission (7-10%). These results indicate that water stress induces root ABA
      accumulation and that this is required for the process of leaf abscission to
      occur. It was also shown that exogenous ABA increases ACC levels in roots but not
      in leaves. Collectively, the data suggest that ABA, the primary sensitive signal
      to water stress, modulates the levels of ethylene, which is the hormonal
      activator of leaf abscission. This assumption implies that root ACC levels are
      correlated with root ABA amounts in a dependent way, which eventually links water
      status to an adequate, protective response such as leaf abscission.

PMID- 12226399
TI  - Cytoplasmic Orientation of the Naphthylphthalamic Acid-Binding Protein in
      Zucchini Plasma Membrane Vesicles.
AB  - Polar transport of the plant hormone auxin is blocked by substances such as N-1
      naphthylphthalamic acid (NPA), which inhibit auxin efflux and block polar auxin
      transport. To understand how auxin transport is regulated in vivo, it is
      necessary to discern whether auxin transport inhibitors act at the intra- or
      extracellular side of the plasma membrane. Populations of predominantly in-side
      in plasma membrane vesicles were subjected to treatments that reverse the
      orientation. These treatments, which included osmotic shock, cycles of freezing
      and thawing, and incubation with 0.05% Brij-58, all increased NPA-binding
      activity and the accessibility of the binding protein to protease digestion.
      Marker activities for inside-out vesicles also increased, indicating that these
      treatments act by altering the membrane orientation. Finally, binding data were
      analyzed by multiple analyses and indicated that neither the affinity nor
      abundance of binding sites changed. Kinetic analyses indicated that the change in
      NPA-binding activity by Brij-58 treatment was due to an increase in the initial
      rates of both association and dissociation of this ligand. These experiments
      indicated that the NPA-binding site is on the cytoplasmic face of the plasma
      membrane in zucchini (Cucurbita pepo L. cv Burpee Fordhook).

PMID- 12226401
TI  - The Electronic Plant Gene Register.

PMID- 12226400
TI  - Correlation of Rapid Cell Death with Metabolic Changes in Fungus-Infected,
      Cultured Parsley Cells.
AB  - To study in detail the hypersensitive reaction, one of the major defense
      responses of plants against microbial infection, we used a model system of
      reduced complexity with cultured parsley (Petroselinum crispum) cells infected
      with the phytopathogenic fungus Phytophthora infestans. Experimental conditions
      were established to maintain maximal viability of the cultured cells during co
      cultivation with fungal germlings, and a large proportion of the infected parsley
      cells responded to fungal infection with rapid cell death, thereby exhibiting
      major features of the hypersensitive reaction in whole-plant-pathogen
      interactions. Rapid cell death clearly correlated with termination of further
      growth and development of the fungal pathogen. Thus, the system fulfilled
      important prerequisites for investigating cell-death-related metabolic changes in
      individual infected cells. Using cytochemical methods, we monitored the increase
      of mitochondrial activity in single infected cells and the intracellular
      accumulation of reactive oxygen species prior to the occurrence of rapid cell
      death. We obtained strong correlative evidence for the involvement of these
      intracellularly accumulating reactive oxygen species in membrane damage and in
      the resulting abrupt collapse of the cell.

PMID- 12226402
TI  - Behavior of Microtubules in Living Plant Cells.

PMID- 12226403
TI  - Transduction of an Ethylene Signal Is Required for Cell Death and Lysis in the
      Root Cortex of Maize during Aerenchyma Formation Induced by Hypoxia.
AB  - Ethylene has been implicated in signaling cell death in the lysigenous formation
      of gas spaces (aerenchyma) in the cortex of adventitious roots of maize (Zea
      mays) subjected to hypoxia. Various antagonists that are known to modify
      particular steps in signal transduction in other plant systems were applied at
      low concentrations to normoxic and hypoxic roots of maize, and the effect on cell
      death (aerenchyma formation) and the increase in cellulase activity that precedes
      the appearance of cell degeneration were measured. Both cellulase activity and
      cell death were inhibited in hypoxic roots in the presence of antagonists of
      inositol phospholipids, Ca2+- calmodulin, and protein kinases. By contrast, there
      was a parallel promotion of cellulase activity and cell death in hypoxic and
      normoxic roots by contact with reagents that activate G-proteins, increase
      cytosolic Ca2+, or inhibit protein phosphatases. Most of these reagents had no
      effect on ethylene biosynthesis and did not arrest root extension. These results
      indicate that the transduction of an ethylene signal leading to an increase in
      intracellular Ca2+ is necessary for cell death and the resulting aerenchyma
      development in roots of maize subjected to hypoxia.

PMID- 12226404
TI  - Tissue-Specific and Light-Mediated Expression of the C4 Photosynthetic NAD
      Dependent Malic Enzyme of Amaranth Mitochondria.
AB  - In the C4 dicotyledonous grain plant amaranth (Amaranthus hypochondriacus), a
      mitochondrial NAD-dependent malic enzyme (NAD-ME; EC 1.1.1.39) serves a
      specialized and essential role in photosynthetic carbon fixation. In this study
      we have examined specialized photosynthetic gene expression patterns for the NAD
      ME [alpha] subunit. We show here that the [alpha] subunit gene is preferentially
      expressed in leaves and cotyledons (the most photosynthetically active tissues),
      and this expression is specific to the bundle-sheath cells of these tissues from
      the earliest stages of development. Synthesis of the [alpha] subunit polypeptide
      and accumulation of its corresponding mRNA are strongly light-dependent, but this
      regulation is also influenced by seedling development. In addition, light
      dependent accumulation of the [alpha] subunit mRNA is regulated at
      transcriptional as well as posttranscriptional levels. Our findings demonstrate
      that the NAD-ME of amaranth has acquired numerous complex tissue-specific and
      light-mediated regulation patterns that define its specialized function as a key
      enzyme in the C4 photosynthetic pathway.

PMID- 12226405
TI  - Expression of the Agrobacterium rhizogenes rolC Gene in a Deciduous Forest Tree
      Alters Growth and Development and Leads to Stem Fasciation.
AB  - We have altered the growth and development of a deciduous forest tree by
      transforming hybrid aspen (Populus tremula x Populus tremuloides) with the
      Agrobacterium rhizogenes rolC gene expressed under the strong cauliflower mosaic
      virus 35S promoter. We demonstrate that the genetically manipulated perennial
      plants, after a period of dormancy, maintain the induced phenotypical changes
      during the second growing period. Furthermore, mass-spectrometrical
      quantifications of the free and conjugated forms of indole-3-acetic acid and
      cytokinins and several gibberellins on one transgenic line correlate the induced
      developmental alterations such as stem fasciation to changes in plant hormone
      metabolism. We also show that the presence of the RolC protein increases the
      levels of the free cytokinins, but not by a process involving hydrolysis of the
      inactive cytokinin conjugates.

PMID- 12226406
TI  - Temporal and Spatial Expression of 1-Aminocyclopropane-1-Carboxylate Oxidase mRNA
      following Pollination of Immature and Mature Petunia Flowers.
AB  - Pollination of petunia (Petunia hybrida) flowers induces a rapid increase in
      ethylene production by styles, which subsequently leads to increased ethylene
      production by the corolla, inducing senescence. We have investigated the temporal
      and spatial expression of 1-aminocyclopropane-1-carboxylate (ACC) oxidase
      transcripts in petunia styles in an attempt to elucidate its role in increased
      ethylene biosynthesis following pollination. Previously, we reported that the
      development of petunia flowers was associated with increased ACC oxidase mRNA
      localized specifically in the stigmatic regions of the style (X. Tang, A.M.T.
      Gomes, A. Bhatia, W.R. Woodson [1994] Plant Cell 6: 1227-1239). The rapid
      increase in ethylene production by styles within the 1st h following pollination
      was correlated with the expression of ACC oxidase mRNAs during development.
      Pollination of petunia flowers prior to anthesis and the expression of ACC
      oxidase mRNA led to a substantial increase in ethylene production, but this was
      delayed by several hours in comparison with flowers at anthesis. This delayed
      increase in ethylene production by pollinated styles from immature flowers was
      associated with an increased ACC oxidase transcript abundance. Treatment with the
      ethylene action inhibitor 2,5-norbornadiene did not affect the early increase in
      ethylene production or the expression of ACC oxidase mRNAs. No differences in the
      rate of pollen germination or tube growth were detected when applied to stigmas
      from immature or mature flowers, indicating that the delay in ethylene production
      was likely the result of limited ACC oxidase activity. Localization of ACC
      oxidase mRNAs following pollination by in situ hybridization revealed an
      abundance of transcripts in transmitting tract tissue within 4 h of pollination
      of both immature and mature styles, in contrast to their localization in
      stigmatic cells during development.

PMID- 12226407
TI  - The Tomato E8 Gene Influences Ethylene Biosynthesis in Fruit but Not in Flowers.
AB  - We investigated the function of the tomato (Lycopersicon esculentum) E8 gene.
      Previous experiments in which antisense suppression of E8 was used suggested that
      the E8 protein has a negative effect on ethylene evolution in fruit. E8 is
      expressed in flowers as well as in fruit, and its expression is high in anthers.
      We introduced a cauliflower mosaic virus 35S-E8 gene into tomato plants and
      obtained plants with overexpression of E8 and plants in which E8 expression was
      suppressed due to co-suppression. Overexpression of E8 in unripe fruit did not
      affect the level of ethylene evolution during fruit ripening; however, reduction
      of E8 protein by cosuppression did lead to elevated levels during ripening.
      Levels for ethylene, 1-aminocyclopropane-1-carboxylic acid (ACC), and ACC oxidase
      mRNA were increased approximately 7-fold in fruit of plants with reduced E8
      protein. Levels of ACC synthase 2 mRNA were increased 2.5-fold, and ACC synthase
      4 mRNA was not affected. Reduction of E8 protein in anthers did not affect the
      accumulation of ACC or of mRNAs encoding enzymes involved in ethylene
      biosynthesis. Our results suggest that the product of the E8 reaction
      participates in feedback regulation of ethylene biosynthesis during fruit
      ripening.

PMID- 12226408
TI  - The Effects of Exogenous Auxins on Endogenous Indole-3-Acetic Acid Metabolism
      (The Implications for Carrot Somatic Embryogenesis).
AB  - The effect of auxin application on auxin metabolism was investigated in excised
      hypocotyl cultures of carrot (Daucus carota). Concentrations of both free and
      conjugated indole-3-acetic acid (IAA), [2H4]IAA, 2,4-dichlorophenoxyacetic acid,
      and naphthaleneacetic acid (NAA) were measured by mass spectroscopy using stable
      isotope-labeled internal standards. [13C1]NAA was synthesized for this purpose,
      thus extending the range of auxins that can be assayed by stable-isotope
      techniques. 2,4-Dichlorophenoxyacetic acid promoted callus proliferation of the
      excised hypocotyls, accumulated as the free form in large quantities, and had
      minor effects on endogenous IAA concentrations. NAA promoted callus proliferation
      and the resulting callus became organogenic, producing both roots and shoots. NAA
      was found mostly in the conjugated form and had minor effects on endogenous IAA
      concentrations. [2H4]IAA had no visible effect on the growth pattern of cultured
      hypocotyls, possibly because it was rapidly metabolized to form inactive
      conjugates or possibly because it mediated a decrease in endogenous IAA
      concentrations by an apparent feedback mechanism. The presence of exogenous
      auxins did not affect tryptophan labeling of either the endogenous tryptophan or
      IAA pools. This suggested that exogenous auxins did not alter the IAA
      biosynthetic pathway, but that synthetic auxins did appear to be necessary to
      induce callus proliferation, which was essential for excised hypocotyls to gain
      the competence to form somatic embryos.

PMID- 12226409
TI  - Posttranscriptional Regulation of the Sesbania rostrata Early Nodulin Gene
      SrEnod2 by Cytokinin.
AB  - The mRNA from the Sesbania rostrata early nodulin gene SrEnod2 accumulates in
      response to cytokinin application. Nuclear run-on assays using isolated root
      nuclei have shown that this accumulation occurs posttranscriptionally, and
      northern blot analysis of nuclear and total RNA levels revealed that it occurs
      primarily in the cytoplasm and not in the nucleus. After cytokinin enhancement of
      SrEnod2 mRNA accumulation and the subsequent removal of cytokinin, the levels of
      SrEnod2 mRNA did not return to basal levels, but oscillated over a 36-h time
      course. Application of the translational inhibitor cycloheximide was found to
      inhibit the enhancement of SrEnod2 mRNA accumulation by cytokinin and to cause
      its rapid decay. Okadaic acid and staurosporine, inhibitors of protein
      phosphatases and kinases, respectively, also inhibited cytokinin enhancement of
      SrEnod2 mRNA accumulation. In addition, okadaic acid was found to cause a
      decrease in SrEnod2 mRNA levels. These results provide evidence for a
      posttranscriptional mechanism of cytokinin enhancement of SrEnod2 mRNA
      accumulation, which appears to require concurrent protein synthesis, to involve
      protein phosphatases and kinases, and to occur primarily in the cytoplasm of the
      plant cell.

PMID- 12226410
TI  - Effect of CO2 Concentration on Carbonic Anhydrase and Ribulose-1,5-Bisphosphate
      Carboxylase/Oxygenase Expression in Pea.
AB  - The effect of external CO2 concentration on the expression of carbonic anhydrase
      (CA) and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) was examined
      in pea (Pisum sativum cv Little Marvel) leaves. Enzyme activities and their
      transcript levels were reduced in plants grown at 1000 [mu]L/L CO2 compared with
      plants grown in ambient air. Growth at 160 [mu]L/L CO2 also appeared to reduce
      steady-state transcript levels for rbcS, the gene encoding the small subunit of
      Rubisco, and for ca, the gene encoding CA; however, rbcS transcripts were reduced
      to a greater extent at this concentration. Rubisco activity was slightly lower in
      plants grown at 160 [mu]L/L CO2, and CA activity was significantly higher than
      that observed in air-grown plants. Transfer of plants from 1000 [mu]L/L to air
      levels of CO2 resulted in a rapid increase in both ca and rbcS transcript
      abundance in fully expanded leaves, followed by an increase in enzyme activity.
      Plants transferred from air to high-CO2 concentrations appeared to modulate
      transcript abundance and enzyme activity less quickly. Foliar carbohydrate levels
      were also examined in plants grown continuously at high and ambient CO2, and
      following changes in growth conditions that rapidly altered ca and rbcS
      transcript abundance and enzyme activities.

PMID- 12226411
TI  - Stimulation of Symbiotic N2 Fixation in Trifolium repens L. under Elevated
      Atmospheric pCO2 in a Grassland Ecosystem.
AB  - Symbiotic N2 fixation is one of the main processes that introduces N into
      terrestrial ecosystems. As such, it may be crucial for the sequestration of the
      extra C available in a world of continuously increasing atmospheric CO2 partial
      pressure (pCO2). The effect of elevated pCO2 (60 Pa) on symbiotic N2 fixation
      (15N-isotope dilution method) was investigated using Free-Air-CO2-Enrichment
      technology over a period of 3 years. Trifolium repens was cultivated either alone
      or together with Lolium perenne (a nonfixing reference crop) in mixed swards. Two
      different N fertilization levels and defoliation frequencies were applied. The
      total N yield increased consistently and the percentage of plant N derived from
      symbiotic N2 fixation increased significantly in T. repens under elevated pCO2.
      All additionally assimilated N was derived from symbiotic N2 fixation, not from
      the soil. In the mixtures exposed to elevated pCO2, an increased amount of
      symbiotically fixed N (+7.8, 8.2, and 6.2 g m-2 a-1 in 1993, 1994, and 1995,
      respectively) was introduced into the system. Increased N2 fixation is a
      competitive advantage for T. repens in mixed swards with pasture grasses and may
      be a crucial factor in maintaining the C:N ratio in the ecosystem as a whole.

PMID- 12226412
TI  - Cool Temperature-Induced Chlorosis in Rice Plants (II. Effects of Cool
      Temperature on the Expression of Plastid-Encoded Genes during Shoot Growth in
      Darkness).
AB  - It has been proposed that cool temperature-induced chlorosis (CTIC) in Indica
      cultivars of rice (Oryza sativa L.) is caused by cell growth and plastid
      development being impeded at cool temperatures. Since it is well known that the
      overall rate of transcription of plastid-encoded genes changes dramatically
      during the early phases of plastid development, in this study we focused on the
      patterns of expression of these genes. Northern blot analysis revealed that the
      level of 16S rRNA is decreased in a CTIC-sensitive rice cultivar grown at a cool
      temperature. The expression of the gene for the [beta] subunit of plasmid RNA
      polymerase (rpoB) was shown to be somewhat disturbed, particularly in terms of
      its resuppression under cool conditions. The level of transcripts or proteins of
      plastid-encoded photosynthetic genes was also decreased in a CTIC-sensitive
      cultivar at a cool temperature. These results suggest that the temperature
      dependent inhibition of the onset of gene expression encoding the
      transcription/translation apparatus may be primarily involved in the mechanism
      causing CTIC.

PMID- 12226413
TI  - Multiple Aluminum-Resistance Mechanisms in Wheat (Roles of Root Apical Phosphate
      and Malate Exudation).
AB  - Although it is well known that aluminum (Al) resistance in wheat (Triticum
      aestivum) is multigenic, physiological evidence for multiple mechanisms of Al
      resistance has not yet been documented. The role of root apical phosphate and
      malate exudation in Al resistance was investigated in two wheat cultivars (Al
      resistant Atlas and Al-sensitive Scout) and two near-isogenic lines (Al-resistant
      ET3 and Al-sensitive ES3). In Atlas Al resistance is multigenic, whereas in ET3
      resistance is conditioned by the single Alt1 locus. Based on root- growth
      experiments, Atlas was found to be 3-fold more resistant in 20 [mu]M Al than ET3.
      Root-exudation experiments were conducted under sterile conditions; a large
      malate efflux localized to the root apex was observed only in Atlas and in ET3
      and only in the presence of Al (5 and 20 [mu]M). Furthermore, the more Al
      resistant Atlas exhibited a constitutive phosphate release localized to the root
      apex. As predicted from the formation constants for the Al-malate and Al
      phosphate complexes, the addition of either ligand to the root bathing solution
      alleviated Al inhibition of root growth in Al-sensitive Scout. These results
      provide physiological evidence that Al resistance in Atlas is conditioned by at
      least two genes. In addition to the alt locus that controls Al-induced malate
      release from the root apex, other genetic loci appear to control constitutive
      phosphate release from the apex. We suggest that both exudation processes act in
      concert to enhance Al exclusion and Al resistance in Atlas.

PMID- 12226414
TI  - Expression of the Cucumber Hydroxypyruvate Reductase Gene Is Down-Regulated by
      Elevated CO2.
AB  - We examined the effects of CO2 concentration on the white-light-stimulated
      expression of the cucumber (Cucumis sativus L.) Hpr gene. Hpr encodes
      hydroxypyruvate reductase, an enzyme important in the photorespiratory glycolate
      pathway, which plays an integral role in carbon allocation in C3 plants. Because
      CO2 is an end product of this pathway and because increased CO2 concentrations
      lessen the need for photorespiration, we tested whether exposure of plants to
      elevated CO2 would affect white-light-stimulated Hpr gene expression. Exposure of
      dark-adapted cucumber seedlings to elevated CO2 (2 to 3 times ambient) during a 4
      h white-light irradiation significantly inhibited the accumulation of Hpr mRNA.
      Increasing the CO2 concentration during irradiation to 6 or 9 times ambient did
      not further inhibit Hpr mRNA accumulation. The depressing effect of high CO2 on
      Hpr mRNA accumulation was seen in both high and low light, but was more
      pronounced in higher light. These results suggest that maximum sensitivity to CO2
      occurs in conditions near those normally encountered by the plant (high light,
      CO2 concentration near ambient) and support a model in which white-light
      regulated Hpr expression is modulated in part by environmental CO2 concentration.

PMID- 12226415
TI  - Identification and Characterization of an Inducible NAD(P)H Dehydrogenase from
      Red Beetroot Mitochondria.
AB  - Exogenous NADH oxidation of mitochondria isolated from red beetroots (Beta
      vulgaris L.) increased dramatically upon slicing and aging the tissue. Anion
      exchange chromatography of soluble fractions derived by sonication from fresh and
      aged beetroot mitochondria yielded three NADH dehydrogenase activity peaks. The
      third peak from aged beetroot mitochondria was separated into two activities by
      blue-affinity chromatography. One of these (the unbound peak) readily oxidized
      dihydrolipoamide, whereas the other (the bound peak) did not. The latter was an
      NAD(P)H dehydrogenase with high quinone and ferricyanide reductase activity and
      was absent from fresh beet mitochondria. Further affinity chromatography of the
      NAD(P)H dehydrogenase indicated enrichment of a 58-kD polypeptide on sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. We propose that this 58-kD
      protein is the inducible, external NADH dehydrogenase.

PMID- 12226416
TI  - Effect of Sulfur Nutrition on the Redistribution of Sulfur in Vegetative Soybean
      Plants.
AB  - Soybean (Glycine max L.) plants were grown with sulfate at 2 (S2) or 20 [mu]M
      (S20) and treated with [35S]sulfate between d 36 and 38. Growth was continued
      with or without 20 [mu]M sulfate (i.e. S2 -> S0, S2 -> S20, etc.). When the
      leaves of S20 -> S20 plants were 70% expanded, they exported S and 35S label from
      the soluble fraction, largely as sulfate, to new expanding leaves. However, 35S
      label in the insoluble fraction was not remobilized. Very little of the 35S label
      in the soluble fraction of the leaves of S20 -> S0 plants was redistributed; most
      was incorporated into the insoluble fraction. The low levels of S remobilization
      from the insoluble fraction were attributed to the high level of N in the
      nutrient solution (15 mM). Most of the 35S label in S2 plants at d 38 occurred in
      the soluble fraction of the roots. In S2 -> S0 plants the 35S label was
      incorporated into the insoluble fraction of the roots, but in S2 -> S20 plants
      35S label was rapidly exported to leaves 3 to 6. It was concluded that the
      soluble fraction of roots contains a small metabolically active pool of S and
      another larger pool that is in slow equilibrium with the small pool.

PMID- 12226417
TI  - Cryopreservation of Chlorophyll Synthesis and Apoprotein Stabilization in Barley
      Etioplasts.
AB  - Methods for the cryopreservation of protein import and integration in pea
      chloroplasts and of protein import or protein synthesis in tobacco mitochondria
      were modified to yield enzymatically active cryopreserved etioplasts from barley
      (Hordeum vulgare L.). The cryoprotectants ethylene glycol and dimethy sulfoxide
      were about 64 and 77% effective, respectively, for the cryopreservation of
      etioplast intactness. Phototransformation of protochlorophyllide a,
      esterification of chlorophyllide a or zinc-pheophorbide a, and stabilization of
      the de novo synthesized plastid-encoded chlorophyll-apoproteins P700, CP47, CP43,
      D2, and D1 were successfully preserved in liquid nitrogen. Cryopreservation of
      freshly prepared intact etioplasts completely retained enzymatic activities for
      accumulation of chlorophyll a or resulted in a slightly decreased yield of zinc
      pheophytin a.

PMID- 12226418
TI  - Coarse and Fine Control and Annual Changes of Sucrose-Phosphate Synthase in
      Norway Spruce Needles.
AB  - Annual changes of activity of sucrose-phosphate synthase (SPS) from spruce (Picea
      abies [L.] Karst.) needles were studied with respect to three regulatory levels:
      metabolic fine control, covalent modification (phosphorylation), and protein
      amount. Glucose-6-phosphate served as an allosteric activator of spruce SPS by
      shifting the Michaelis constant for the substrate fructose-6-phosphate from 4.2
      to 0.59 mM, whereas inorganic phosphate competitively inhibited this activation.
      The affinity for the other substrate, UDP-glucose, was unaffected. Incubation of
      the crude extract with ATP resulted in a time- and concentration-dependent
      decrease of the maximal velocity of SPS. This inactivation was sensitive to
      staurosporine, a potent protein kinase inhibitor, indicating the participation of
      a protein kinase. Probing SPS protein with heterologous antibodies showed that
      the subunit of spruce SPS is an approximately 139-kD protein and that changes in
      the extractable activity during the course of a year were correlated with the
      amount of SPS protein. High SPS activities in winter were paralleled by increased
      levels of the activator glucose-6-phosphate and the substrate fructose-6
      phosphate, indicating a high capacity for sucrose synthesis that may be necessary
      to maintain photosynthetic CO2 fixation in cold-hardened spruce needles.

PMID- 12226419
TI  - Subcellular Location of O-Acetylserine Sulfhydrylase Isoenzymes in Cell Cultures
      and Plant Tissues of Datura innoxia Mill.
AB  - O-Acetylserine sulfhydrylase (OASS; EC 4.2.99.8) catalyzes the formation of L
      cysteine from O-acetylserine and inorganic sulfide. Three OASS isoenzymes that
      differ in molecular mass and subunit structure are present in shoot and root
      tissues and in cadmium-resistant and cadmium-susceptible cell cultures of Datura
      innoxia Mill. Different OASS forms predominate in leaves, roots, and suspension
      cell cultures. To determine the subcellular location of the OASS isoenzymes,
      purified mitochondria, chloroplasts, and cytosolic fractions from protoplasts
      were obtained. The isoenzymes are compartmentalized in D. innoxia cells, with a
      different isoenzyme predominant in the chloroplast, cytosol, and mitochondria,
      suggesting that they serve different functions in the plant cell. The chloroplast
      form is most abundant in green leaves and leaf protoplasts. The cytosolic form is
      most abundant in roots and cell cultures. A mitochondrial form is abundant in
      cell cultures, but is a minor form in leaves or roots. Cadmium-tolerant cell
      cultures contain 1.8 times as much constitutive OASS activity as the wild-type
      cell line, and 2.9 times more than the cadmium-hypersensitive cell line. This may
      facilitate rapid production of glutathione and metal-binding phytochelatins when
      these cultures are exposed to cadmium.

PMID- 12226420
TI  - Stress Responses in Alfalfa (XXI. Activation of Caffeic Acid 3-O
      Methyltransferase and Caffeoyl Coenzyme A 3-O-Methyltransferase Genes Does Not
      Contribute to Changes in Metabolite Accumulation in Elicitor-Treated Cell
      Suspension Cultures).
AB  - Transcription of genes encoding L-phenylalanine ammonia-lyase (PAL), the first
      enzyme of the phenylpropanoid pathway, and caffeic acid 3-O-methyltransferase
      (COMT) and caffeoyl CoA 3-O-methyltransferase (CCOMT), enzymes involved in the
      synthesis of lignin and wall-esterified phenolic compounds, was strongly
      activated in elicitor-treated cell-suspension cultures of alfalfa (Medicago
      sativa L.). However, consequent changes in the extractable activities of COMT and
      CCOMT were small to nonexistent compared with a 15- to 16-fold increase in PAL
      activity. Only low levels of COMT and CCOMT transcripts were reflected in the
      total and polysomal RNA fractions compared with PAL transcripts. Elicited cell
      cultures did not accumulate lignin or the products of COMT and CCOMT in the
      soluble and wall-esterified phenolic fractions. In one alfalfa cell line in which
      elicitation resulted in very high PAL activity and increased deposition of
      methoxyl groups in the insoluble wall fraction, there was still no change in COMT
      and CCOMT activities. Overall, these results indicate that the initial gene
      transcription events in elicited cells may be less selective than the subsequent
      metabolic changes, highlighting the importance of posttranscriptional events in
      the control of phenylpropanoid biosynthesis.

PMID- 12226421
TI  - Transport of Salicylic Acid in Tobacco Necrosis Virus-Infected Cucumber Plants.
AB  - The transport of salicylic acid (SA) was studied in cucumber (Cucumis sativus L.)
      using 14C-labeled benzoic acid that was injected in the cotyledons at the time of
      inoculation. Primary inoculation with tobacco necrosis virus (TNV) on the
      cotyledons led to an induction of systemic resistance of the first primary leaf
      above the cotyledon against Colletotrichum lagenarium as early as 3 d after
      inoculation. [14C]SA was detected in the phloem or in the first leaf 2 d after
      TNV inoculation, whereas [14C]benzoic acid was not detected in the phloem during
      the first 3 d after TNV inoculation of the cotyledons, indicating phloem
      transport of [14C]SA from cotyledon. In leaf 1, the specific activity of [14C]SA
      decreased between 1.7 and 8.6 times compared with the cotyledons, indicating
      that, in addition to transport, leaf 1 also produced more SA. The amount of SA
      transported after TNV infection of the cotyledon was 9 to 160 times higher than
      in uninfected control plants. Thus, SA can be transported to leaf 1 before the
      development of systemic acquired resistance, and SA accumulation in leaf 1
      results both from transport from the cotyledon and from synthesis in leaf 1.

PMID- 12226422
TI  - Antioxidant Response to NaCl Stress in a Control and an NaCl-Tolerant Cotton Cell
      Line Grown in the Presence of Paraquat, Buthionine Sulfoximine, and Exogenous
      Glutathione.
AB  - A cotton (Gossypium hirsutum L.) control and NaCl-tolerant cell line (cv Coker
      312) were grown on media with or without NaCl in the presence or absence of
      paraquat, buthionine sulfoximine, and oxidized glutathione. On medium with 150 mM
      NaCl the NaCl-tolerant cell line exhibited no reduction in growth, whereas a 96%
      reduction was observed in the control line. The NaCl-tolerant cell line that was
      grown on 150 mM NaCl exhibited significantly greater catalase (341%), peroxidase
      (319%), glutathione reductase (287%), ascorbate peroxidase (450%), [gamma]
      glutamylcysteine synthetase (224%), and glutathione S-transferase (500%)
      activities than the intolerant control. The NaCl-tolerant cell line had a
      significantly lower dehydroascorbic acid/ascorbic acid ratio. Paraquat reduced
      growth by 20 and 53.7%, respectively, in the NaCl-tolerant and control cell line.
      The NaCl-tolerant cell line also showed a slight tolerance to buthionine
      sulfoximine. In the buthionine sulfoximine experiments reduced glutathione
      restored growth in both cell lines, whereas oxidized glutathione restored growth
      only in the NaCl-tolerant cell line. These data indicate that the NaCl-tolerant
      cell line exhibited a cross-tolerance to a variety of stress variables and had a
      more active ascorbate-glutathione cycle.

PMID- 12226423
TI  - Localized Wounding by Heat Initiates the Accumulation of Proteinase Inhibitor II
      in Abscisic Acid-Deficient Plants by Triggering Jasmonic Acid Biosynthesis.
AB  - To test whether the response to electrical current and heat treatment is due to
      the same signaling pathway that mediates mechanical wounding, we analyzed the
      effect of electric-current application and localized burning on proteinase
      inhibitor II (Pin2) gene expression in both wild-type and abscisic acid (ABA)
      deficient tomato (Lycopersicon esculentum Mill.) and potato (Solanum phureja)
      plants. Electric-current application and localized burning led to the
      accumulation of Pin2 mRNA in potato and tomato wild-type plants. Among the
      treatments tested, only localized burning of the leaves led to an accumulation of
      Pin2 mRNA in the ABA-deficient plants. Electric-current application, like
      mechanical injury, was able to initiate ABA and jasmonic acid (JA) accumulation
      in wild-type but not in ABA-deficient plants. In contrast, heat treatment led to
      an accumulation of JA in both wild-type and ABA-deficient plants. Inhibition of
      JA biosynthesis by aspirin blocked the heat-induced Pin2 gene expression in
      tomato wild-type leaves. These results suggest that electric current, similar to
      mechanical wounding, requires the presence of ABA to induce Pin2 gene expression.
      Conversely, burning of the leaves activates Pin2 gene expression by directly
      triggering the biosynthesis of JA by an alternative pathway that is independent
      of endogenous ABA levels.

PMID- 12226424
TI  - Elicitation of Plant Hypersensitive Response by Bacteria.

PMID- 12226425
TI  - Effects of Epidermal Cell Shape and Pigmentation on Optical Properties of
      Antirrhinum Petals at Visible and Ultraviolet Wavelengths.
AB  - We used the Mixta+ and mixta- lines of Antirrhinum majus as a model system to
      investigate the effects of epidermal cell shape and pigmentation on tissue
      optical properties in the visible and ultraviolet (UV) spectral regions. Adaxial
      epidermal cells of Mixta+ flowers have a conical-papillate shape; in the mixta-
      line the cells are slightly domed. Mixta+ cells contained significantly more
      anthocyanin and other flavonoids than mixta- cells when plants were grown under
      either high- or low-UV conditions. Mixta+ cells focused light (3.5-4.7 times
      incident) within their pigmented interiors, whereas mixta- cells focused light
      (2.1-2.7 times incident) in the unpigmented mesophyll. UV light penetrated the
      epidermis (commonly 20-50% transmittance at 312 nm) mainly through the
      unpigmented peripheral regions of the cells that were similar for the two lines,
      so that overall penetration through Mixta+ and mixta- epidermises was equal.
      However, maximum UV absorption in the central region of epidermal cells was
      slightly greater in Mixta+ than mixta-, and intact Mixta+ flowers reflected less
      light in the spectral regions with intermediate flavonoid absorbance. In both
      cases, about 50 to 75% of the difference could be attributed to cell shape and
      resulting changes in the optical pathlength or focusing.

PMID- 12226426
TI  - Stomatal Guard Cells Are Totipotent.
AB  - It has been successfully demonstrated, using epidermis explants of sugar beet
      (Beta vulgaris L.), that stomatal guard cells retain full totipotent capacity.
      Despite having one of the highest degrees of morphological adaptation and a
      unique physiological specialization, it is possible to induce a re-expression of
      full (embryogenic) genetic potential in these cells in situ by reversing their
      highly differentiated nature to produce regenerated plants via a callus stage.
      The importance of these findings both to stomatal research and to our
      understanding of cytodifferentiation in plants is discussed.

PMID- 12226427
TI  - Induction of Defense-Related Ultrastructural Modifications in Pea Root Tissues
      Inoculated with Endophytic Bacteria.
AB  - The stimulation exerted by the endophytic bacterium Bacillus pumilus strain SE34
      in plant defense reactions was investigated at the ultrastructural level using an
      in vitro system in which root-inducing T-DNA pea (Pisum sativum L.) roots were
      infected with the pea root-rotting fungus Fusarium oxysporum f. sp. pisi. In
      nonbacterized roots, the pathogen multiplied abundantly through much of the
      tissue including the vascular stele, whereas in prebacterized roots, pathogen
      growth was restricted to the epidermis and the outer cortex In these
      prebacterized roots, typical host reactions included strengthening the epidermal
      and cortical cell walls and deposition of newly formed barriers beyond the
      infection sites. Wall appositions were found to contain large amounts of callose
      in addition to being infiltrated with phenolic compounds. The labeling pattern
      obtained with the gold-complexed laccase showed that phenolics were widely
      distributed in Fusarium-challenged, bacterized roots. Such compounds accumulated
      in the host cell walls and the intercellular spaces as well as at the surface or
      even inside of the invading hyphae of the pathogen. The wall-bound chitin
      component in Fusarium hyphae colonizing bacterized roots was preserved even when
      hyphae had undergone substantial degradation. These observations confirm that
      endophytic bacteria may function as potential inducers of plant disease
      resistance.

PMID- 12226428
TI  - Lhcb Transcription Is Coordinated with Cell Size and Chlorophyll Accumulation
      (Studies on Fluorescence-Activated, Cell-Sorter-Purified Single Cells from Wild
      Type and immutans Arabidopsis thaliana).
AB  - To study the mechanisms that integrate pigment and chlorophyll a/b-binding
      apoprotein biosynthesis during light-harvesting complex II assembly, we have
      examined [beta]-glucuronidase (GUS) enzyme activities, chlorophyll contents, and
      cell sizes in fluorescence-activated, cell-sorting-separated single cells from
      transgenic Arabidopsis thaliana wild-type and immutans variegation mutant plants
      that express an Lhcb (photosystem II chlorophyll a/b-binding polypeptide
      gene)/GUS promoter fusion. We found that GUS activities are positively correlated
      with chlorophyll content and cell size in green cells from the control and
      immutans plants, indicating that Lhcb gene transcription is coordinated with cell
      size in this species. Compared with the control plants, however, chlorophyll
      production is enhanced in the green cells of immutans; this may represent part of
      a strategy to maximize photosynthesis in the green sectors to compensate for a
      lack of photosynthesis in the white sectors of the mutant. Lhcb transcription is
      significantly higher in pure-white cells of the transgenic immutans plants than
      in pure-white cells from norflurazon-treated, photooxidized A. thaliana leaves.
      This suggests that immutans partially uncouples Lhcb transcription from its
      normal dependence on chlorophyll accumulation and chloroplast development. We
      conclude that immutans may play a role in regulating Lhcb transcription, and may
      be a key component in the signal transduction pathways that control chloroplast
      biogenesis.

PMID- 12226429
TI  - Interactions between Photosynthesis and Respiration in the Green Alga
      Chlamydomonas reinhardtii (Characterization of Light-Enhanced Dark Respiration).
AB  - The rate of respiratory O2 consumption by Chlamydomonas reinhardtii cell
      suspensions was greater after a period of photosynthesis than in the preceding
      dark period. This "light-enhanced dark respiration" (LEDR) was a function of both
      the duration of illumination and the photon fluence rate. Mass spectrometric
      measurements of gas exchange indicated that the rate of gross respiratory O2
      consumption increased during photosynthesis, whereas gross respiratory CO2
      production decreased in a photon fluence rate-dependent manner. The rate of
      postillumination O2 consumption provided a good measure of the O2 consumption
      rate in the light. LEDR was substantially decreased by the presence of 3-(3,4
      dichlorophenyl)-1,1-dimethylurea or glycolaldehyde, suggesting that LEDR was
      photosynthesis-dependent. The onset of photosynthesis resulted in an increase in
      the cellular levels of phosphoglycerate, malate, and phosphoenolpyruvate, and a
      decrease in whole-cell ATP and citrate levels; all of these changes were rapidly
      reversed upon darkening. These results are consistent with a decrease in the rate
      of respiratory carbon flow during photosynthesis, whereas the increase in
      respiratory O2 consumption during photosynthesis may be mediated by the export of
      photogenerated reductant from the chloroplast. We suggest that photosynthesis
      interacts with respiration at more than one level, simultaneously decreasing the
      rate of respiratory carbon flow while increasing the rate of respiratory O2
      consumption.

PMID- 12226430
TI  - Characterization of Hypoxically Inducible Lactate Dehydrogenase in Maize.
AB  - Oxygen deprivation induces a wide variety of genes, but the most extensively
      studied are those encoding enzymes of the glycolytic pathway. Lactate
      dehydrogenase (LDH, EC 1.1.1.27) activity increases up to 3.5-fold in maize (Zea
      mays L.) roots during several days of hypoxic induction. This increase in
      activity is accompanied by a decrease in in vitro enzyme stability. LDH activity
      in aerobic root extracts has an in vitro half-life of 240 min, decreasing to 100
      min in 72-h hypoxically induced plant root extracts. The increase in enzyme
      activity during hypoxic induction is the result of increased protein levels,
      which correlate with increased transcript levels. Two ldh transcripts of 1.3 and
      1.7 kb are induced, with maximum levels reached by 8 and 24 h, respectively. This
      suggests that the two ldh genes are differentially regulated. Treatment with the
      protein synthesis inhibitor cycloheximide does not preclude ldh induction during
      the first few hours of hypoxic stress, suggesting that new protein synthesis may
      not be essential for elevation of ldh transcript levels under hypoxic conditions.
      The rapid and substantial increase in ldh mRNA levels under hypoxic conditions
      and in the presence of cycloheximide suggests that the ldh gene may be valuable
      in analyzing the hypoxic signal transduction pathway.

PMID- 12226431
TI  - Changes in Cytokinin Content and Cytokinin Oxidase Activity in Response to
      Derepression of ipt Gene Transcription in Transgenic Tobacco Calli and Plants.
AB  - Metabolic control of cytokinin oxidase by its substrate was investigated in
      planta using wild-type (WT) and conditionally ipt gene-expressing transgenic
      (IPT) tobacco (Nicotiana tabacum L.) callus cultures and plants. The derepression
      of the tetracycline (Tc)-dependent ipt gene transcription was followed by a
      progressive, more than 100-fold increase in total cytokinin content in IPT calli.
      The activity of cytokinin oxidase extracted from these calli began to increase 16
      to 20 h after gene derepression, and after 13 d it was 10-fold higher than from
      Tc-treated WT calli. An increase in cytokinin oxidase activity, as a consequence
      of elevated cytokinin levels, was found in detached leaves (8-fold after 4 d) and
      in roots of intact plants (4-fold after 3 d). The partially purified cytokinin
      oxidase from WT, repressed IPT, and Tc-derepressed IPT tobacco calli exhibited
      similar characteristics. It had the same broad pH optimum (pH 6.5-8.5), its
      activity in vitro was enhanced 4-fold in the presence of copper-imidazole, and
      the apparent Km(N6-[[delta]2iso-pentenyl]adenine) values were in the range of 3.1
      to 4.9 [mu]M. The increase in cytokinin oxidase activity in cytokinin
      overproducing tissue was associated with the accumulation of a glycosylated form
      of the enzyme. The present data indicate the substrate induction of cytokinin
      oxidase activity in different tobacco tissues, which may contribute to hormone
      homeostasis.

PMID- 12226432
TI  - Analyzing the Light Energy Distribution in the Photosynthetic Apparatus of C4
      Plants Using Highly Purified Mesophyll and Bundle-Sheath Thylakoids.
AB  - The chlorophyll fluorescence characteristics of mesophyll and bundle-sheath
      thylakoids from plant species with the C4 dicarboxylic acid pathway of
      photosynthesis were investigated using flow cytometry. Ten species with the NADP
      malic enzyme (NADP-ME) biochemical type of C4 photosynthesis were tested:
      Digitaria sanguinalis (L.) Scop., Euphorbia maculata L., Portulaca grandiflora
      Hooker, Saccharum officinarum L., Setaria viridis (L.) Beauv., Zea mays L., and
      four species of the genus Flaveria. This study also included three species with
      NAD-ME biochemistry (Atriplex rosea L., Atriplex spongiosa F. Muell., and
      Portulaca oleracea L.). Two C4 species of unknown biochemical type were
      investigated: Cyperus papyrus L. and Atriplex tatarica L. Pure mesophyll and
      bundle-sheath thylakoids were prepared by flow cytometry and characterized by low
      temperature fluorescence spectroscopy. In pure bundle-sheath thylakoids from many
      species with C4 photosynthesis of the NADP-ME type, significant amounts of
      photosystem II (PSII) emission can be detected by fluorescence spectroscopy.
      Simulation of fluorescence excitation spectra of these thylakoids showed that
      PSII light absorption contributes significantly to the apparent excitation
      spectrum of photosystem I. Model calculations indicated that the excitation
      energy of PSII is efficiently transferred to photosystem I in bundle-sheath
      thylakoids of many NADP-ME species.

PMID- 12226433
TI  - Synthesis of Glutathione in Leaves of Transgenic Poplar Overexpressing [gamma]
      Glutamylcysteine Synthetase.
AB  - Internode stem fragments of the poplar hybrid Populus tremula x Populus alba were
      transformed with a bacterial gene (gshl) for [gamma]-glutamylcysteine synthetase
      ([gamma]-ECS) targeted to the cytosol. Lines overexpressing [gamma]-ECS were
      identified by northern analysis, and the transformant with the highest enzyme
      activity was used to investigate the control of glutathione synthesis. Whereas
      foliar [gamma]-ECS activity was below the limit of detection in untransformed
      plants, activities of up to 8.7 nmol mg-1 protein min-1 were found in the
      transformant, in which the foliar contents of [gamma]-glutamylcysteine ([gamma]
      EC) and glutathione were increased approximately 10- and 3-fold, respectively,
      without affecting either the reduction state of the glutathione pool or the
      foliar cysteine content. A supply of exogenous cysteine to leaf discs increased
      the glutathione content from both transformed and untransformed poplars, and
      caused the [gamma]-EC content of the transformant discs to increase still
      further. The following conclusions are drawn: (a) the native [gamma]-ECS of
      untransformed poplars exists in quantities that are limiting for foliar
      glutathione synthesis; (b) foliar glutathione synthesis in untransformed poplars
      is limited by cysteine availability; (c) in the transformant interactions between
      glutathione synthesis and cysteine synthesis operate to sustain the increased
      formation of [gamma]-EC and glutathione; and (d) the foliar glutathione content
      of the transformant is restricted by cysteine availability and by the activity of
      glutathione synthetase.

PMID- 12226434
TI  - Evidence for Opposing Effects of Calmodulin on Cortical Microtubules.
AB  - Microtubule integrity within the cortical array was visualized in detergent-lysed
      carrot (Daucus carota L.) protoplasts that were exposed to various exogenous
      levels of Ca2+ and calmodulin (CaM). CaM appears to help stabilize cortical
      microtubules against the destabilizing action of Ca2+/CaM complexes at low Ca2+
      concentrations, but not at higher Ca2+ concentrations. The hypothesis that CaM
      interacts with microtubules at two different sites, determined by the
      concentration of Ca2+, is supported by the effects of the CaM antagonists N-(6
      aminohexyl)-1-naphthalene-sulfonamide and N-(6-aminohexyl)-5-chloro-1
      naphthalenesulfanamide (20 [mu]M) and by affinity chromatography. Two classes of
      proteins were identified that interact with tubulin and bind to CaM. One class
      required Ca2+ for CaM binding, whereas the second class bound only when Ca2+
      concentrations were low (<320 nM). Thus, CaM's ability to have two opposing
      effects upon microtubules may be regulated by the concentration of intracellular
      Ca2+ and its differential interactions with microtubule-associated proteins.
      Experimental manipulation of intracellular Ca2+ concentrations, as monitored by
      Indo-1, revealed that the effect of Ca2+ is specific to the cortical microtubules
      and does not affect actin microfilaments in these cells.

PMID- 12226435
TI  - Induction of a Pea Cell-Wall Invertase Gene by Wounding and Its Localized
      Expression in Phloem.
AB  - A full-length cell-wall invertase cDNA obtained from pea (Pisum sativum L.)
      seedlings was cloned previously. The gene exhibits tissue-specific expression,
      and both its transcript and enzyme activities are abundant only in root tissues.
      Mechanical wounding dramatically induced the accumulation of the cell-wall
      invertase mRNA in detached or intact leaves, stems, and roots. In both detached
      and intact tissues mRNA started to accumulate 3 h after wounding and in detached
      tissues (except root tissues) was much stronger and lasted longer compared with
      that in intact pea plants. The induction of cell-wall invertase by wounding was
      not systemic, since no significant increase of transcript was found in the
      unwounded tissues remote from the site of wounding. Accumulation of this cell
      wall invertase was induced by abscisic or jasmonic acid, and in situ
      hybridization studies show that this invertase mRNA is differentially localized
      in wounded plant tissue, being most abundant in the phloem. mRNA accumulation was
      limited mainly to the wounded area; no significant increase was detected in the
      unwounded portions of the wounded stem segments. The results suggest that, as
      part of the wounding response, this cell-wall invertase may provide energy
      through hexose availability to companion cells in the phloem.

PMID- 12226436
TI  - Role of Apoplastic and Cell-Wall Peroxidases on the Stimulation of Root
      Elongation by Ascorbate.
AB  - Elongation of onion (Allium cepa L.) roots was highly stimulated by ascorbate
      (ASC) and its natural precursor I-galactone-[gamma]-lactone (GL). When incubation
      media were supplemented with lycorine (Lyc), an inhibitor of the ASC
      biosynthesis, root growth was negligible even in the presence of ASC or GL. ASC
      completely inhibited in vitro guaiacol peroxidase activities that were isolated
      from both the apoplast and the cell wall. However, ferulic-acid-dependent
      peroxidase from the cell wall was partially inhibited by ASC, whereas ferulic
      acid peroxidase activity from the apoplastic fluid was completely inhibited by
      ASC as long as ASC was present in the assay medium. ASC content in cells was
      increased by preincubations with ASC or GL, whereas Lyc reduced it. On the other
      hand, ASC or GL treatments decreased both apoplast and cell-wall-bound peroxidase
      activities, whereas Lyc had a slight stimulating effect. These results are
      discussed on the basis of a possible control of root elongation by ASC via its
      action on peroxidases that are involved in the regulation of cell-wall
      extensibility.

PMID- 12226437
TI  - Root Growth Inhibition in Boron-Deficient or Aluminum-Stressed Squash May Be a
      Result of Impaired Ascorbate Metabolism.
AB  - Although cessation of growth is the most apparent symptom of boron deficiency,
      the biochemical function of boron in growth processes is not well understood. We
      propose that the action of boron in root meristems is associated with ascorbate
      metabolism. Total inhibition of root growth in squash (Cucurbita pepo L.) plants
      transferred to boron-free medium coincided with a major decrease (up to 98%) in
      the ascorbate concentration of root apices. Under low-boron conditions, in which
      root growth was partially inhibited, ascorbate concentration declined in
      proportion to growth rate. The decline in ascorbate concentration in boron
      deficient root tips was not related to ascorbate oxidation. Ascorbate added to
      the medium improved root growth in plants supplied with insufficient boron.
      Increasing concentrations of aluminum in the nutrient medium caused progressive
      inhibition of root growth and a parallel reduction in ascorbate concentration of
      root apices. Elevated boron levels improved root growth under toxic aluminum
      conditions and produced root apices with higher ascorbate concentrations. To our
      knowledge, this is the first report of a correlation between boron nutrition,
      ascorbate concentration in root apices, and growth. These findings show that root
      growth inhibition resulting from either boron deficiency or aluminum toxicity may
      be a consequence of disrupted ascorbate metabolism.

PMID- 12226438
TI  - Evidence for Substrate Induction of a Nitrate Efflux System in Barley Roots.
AB  - Induction of an NO3- efflux system in intact barley (Hordeum vulgare L.) roots
      was demonstrated. Since the measurement of NO3- efflux is dependent on its
      accumulation, experiments were devised to facilitate accumulation under
      noninducing conditions. This was accomplished by incubating seedlings in 10 mM
      NO3- in the presence of RNA and protein synthesis inhibitors. Under these
      conditions NO3- uptake is mediated by constitutive high- and low-affinity
      transport systems. Control roots were incubated with 1.0 mM NO3-. This resulted
      in the accumulation of similar levels of NO3- in both treated and control roots;
      however, cytoplasmic NO3- efflux from inhibitor-treated roots was much lower than
      from control roots. Following a brief lag period, efflux rates increased rapidly
      in the presence of NO3- for 8 to 12 h. The NO3- efflux system was also induced by
      ambient NO2-. After induction the efflux system was relatively stable in the
      presence of RNA and protein synthesis inhibitors as long as NO3- or NO2- was
      present. These results suggest that NO3- efflux may be an inducible system
      requiring both RNA and protein synthesis, as does induction of the uptake system.
      The efflux system, however, has a much slower turnover rate than the uptake
      system.

PMID- 12226439
TI  - An Inducible Glutathione S-Transferase in Soybean Hypocotyl Is Localized in the
      Apoplast.
AB  - Glutathione S-transferases (GSTs) with additional activities as fatty acid
      hydroperoxidases were investigated in soybean (Glycine max L.) hypocotyls. Aside
      from the GSTs present in total soluble tissue extracts, enzyme activities and
      distinct immunoreactive GST polypeptides were also detected in the intercellular
      washing fluid. Whereas the intracellular isoenzymes were both constitutive and
      inducible, apoplastic GST and glutathione peroxidase was detectable only in
      tissues treated with the known GST inducer 2,3,5-triiodobenzoic acid. Monensin
      inhibited the induced accumulation of apoplastic GST but did not affect the
      intracellular isoforms. The discovery of apoplastic inducible GST will be
      discussed in light of the putative function of these enzymes in plants.

PMID- 12226440
TI  - Characterization of the Endoproteases Appearing during Wheat Grain Development.
AB  - The pattern of endoproteolytic activities occurring during wheat (Triticum
      aestivum, cultivar Chinese Spring) grain development was investigated. Total
      endoprotease activity, assayed in solution with azocasein as a substrate,
      increased during the early stages of grain development to reach a maximum at 15 d
      postanthesis that was maintained until the grain was mature. Endoprotease
      activity was also assayed in gradient polyacrylamide gels co-polymerized with
      gelatin. The increase in endoproteolytic activity was due to the appearance of up
      to 18 endoproteolytic bands that were arbitrarily classified into five groups (A,
      B, C, D, and E). The presence of serine, aspartic, metallo, and, to a lesser
      extent, thiol proteases in developing wheat grains was demonstrated by the use of
      class-specific protease inhibitors. The appearance of the different classes of
      endoproteases during seed development was subject to temporal control; serine
      proteases were more abundant at early stages and aspartic and metallo proteases
      were more abundant at later stages. At intermediate stages of development (15-20
      d postanthesis), most of the endoproteases were localized in the aleurone, testa,
      and embryo. The content of acidic thiol proteases was low in the developing
      starchy endosperm.

PMID- 12226441
TI  - Arginase, Arginine Decarboxylase, Ornithine Decarboxylase, and Polyamines in
      Tomato Ovaries (Changes in Unpollinated Ovaries and Parthenocarpic Fruits Induced
      by Auxin or Gibberellin).
AB  - Arginase (EC 3.5.3.1) activity has been found in the ovaries and Young fruits of
      tomato (Lycopersicon esculentum Mill. cv Rutgers).Changes in arginase, arginine
      decarboxylase (EC 4.1.1.19), and ornithine decarboxylase activity (EC 4.1.1.17)
      and levels of free and conjugated putrescine, spermidine, and spermine were
      determined in unpollinated ovaries and in parthenocarpic fruits during the early
      stages of development induced by 2,4-dichlorophenoxyacetic acid (2,4-D) or
      gibberellic acid (GA3). Levels of arginase, free spermine, and conjugates of the
      three polyamines were constant in unpollinated ovaries and characteristic of a
      presenescent step. A marked decrease in arginase activity, free spermine, and
      polyamine conjugates was associated with the initiation of fruit growth due to
      cell division, and when cell expansion was initiated, the absence of arginase
      indicated a redirection of nitrogen metabolism to the synthesis of arginine. A
      transient increase in arginine decarboxylase and ornithine decarboxylase was also
      observed in 2,4-D-induced fruits. In general, 2,4-D treatments produced faster
      changes than GA3, and without treatment, unpollinated ovaries developed only
      slightly and senescence was hardly visible. Sensitivity to 2,4-D and GA3
      treatment remained for at least 2 weeks postanthesis.

PMID- 12226442
TI  - Effect of High Temperature on Photosynthesis in Beans (I. Oxygen Evolution and
      Chlorophyll Fluorescence).
AB  - We studied the effect of increasing temperature on photosynthesis in two bean
      (Phaseolus vulgaris L.) varieties known to differ in their resistance to extreme
      high temperatures, Blue Lake (BL), commercially available in the United Kingdom,
      and Barbucho (BA), noncommercially bred in Chile. We paid particular attention to
      the energy-transducing mechanisms and structural responses inferred from
      fluorescence kinetics. The study was conducted in non-photorespiratory
      conditions. Increases in temperature resulted in changes in the fluorescence
      parameters nonphotochemical quenching (qN) and photochemical quenching (qP) in
      both varieties, but to a different extent. In BL and BA the increase in qP and
      the decrease in qN were either completed at 30[deg]C or slightly changed
      following increases from 30 to 35[deg]C. No indication of photoinhibition was
      detected at any temperature, and the ratio of the quantum efficiencies of
      photosystem II (PSII) and O2 evolution remained constant from 20 to 35[deg]C.
      Measurements of 77-K fluorescence showed an increase in the photosystem I
      (PSI)/PSII ratio with temperature, suggesting an increase in the state
      transitions. In addition, measurements of fast-induction fluorescence revealed
      that the proportion of PSII[beta] centers increased with increasing temperatures.
      The extent of both changes were maximum at 30 to 35[deg]C, coinciding with the
      ratio of rates at temperatures differing by 10[deg]C for oxygen evolution.

PMID- 12226443
TI  - Effect of High Temperature on Photosynthesis in Beans (II. CO2 Assimilation and
      Metabolite Contents).
AB  - The effect of high temperatures on CO2 assimilation, metabolite content, and
      capacity for reducing power production in non-photorespiratory conditions has
      been assessed in two different bean (Phaseolus vulgarus L.) varieties, Blue Lake
      (commercially available in the United Kingdom) and Barbucho (a noncommercially
      bred Chilean variety), which are known to differ in their resistance to extreme
      high temperatures. Barbucho maintains its photosynthetic functions for a longer
      period of time under extreme heat compared with Blue Lake. The CO2 assimilation
      rate was increased by increases in temperature, with a decrease in ratio of rates
      of temperatures differing by 10[deg]C. It is suggested that limitations to CO2
      assimilation are caused by metabolic restrictions that can be differentiated
      between those occurring in the range of 20 to 30[deg]C and 30 to 35[deg]C. It is
      likely that changes in the capacity for Calvin cycle regeneration and starch
      synthesis affect photosynthesis in the range of 20 to 30[deg]C. But following an
      increase in temperature from 30 to 35[deg]C, the supply of reducing power becomes
      limiting. From analysis of adenylate concentration, transthylakoid energization,
      and, indirectly, NADPH/NADP+ ratio, it was concluded that the limitation in the
      assimilatory power was due to an oxidation of the NADPH/NADP+ pool. In the range
      of 30 to 35[deg]C, the photosystem I quantum yield increased and photosystem II
      maintained its value. We conclude that the reorganization of thylakoids observed
      at 30 to 35[deg]C increased the excitation of photosystem I, inducing an increase
      in cyclic electron transport and a decrease in the supply of NADPH, limiting
      carbon assimilation.

PMID- 12226444
TI  - Heterogeneity of Arabinogalactan-Proteins on the Plasma Membrane of Rose Cells.
AB  - Arabinogalactan-proteins (AGPs) have been purified from the plasma membrane of
      suspension-cultured Paul's Scarlet rose (Rosa sp.) cells. The two most abundant
      and homogeneous plasma membrane AGP fractions were named plasma membrane AGP1 (PM
      AGP1) and plasma membrane AGP2 (PM-AGP2) and had apparent molecular masses of 140
      and 217 kD, respectively. Both PM-AGP1 and PM-AGP2 had [beta]-(1-3)-, [beta]
      (1,6)-, and [beta]-(1,3,6)-galactopyranosyl residues, predominantly terminal
      [alpha]-arabinofuranosyl residues, and (1,4)- and terminal glucuronopyranosyl
      residues. The protein moieties of PM-AGP1 and PM-AGP2 were both rich in
      hydroxyproline, alanine, and serine, but differed in the abundance of
      hydroxyproline, which was 1.6 times higher in PM-AGP2 than in PM-AGP1. Another
      difference was the overall protein content, which was 3.7% (w/w) in PM-AGP1 and
      15% in PM-AGP2. As judged by their behavior on reverse-phase chromatography, PM
      AGP1 and PM-AGP2 were not more hydrophobic than AGPs from the cell wall or
      culture medium. In contrast, a minor plasma membrane AGP fraction eluted later on
      reverse-phase chromatography and was more negatively charged at pH 5 than either
      PM-AGP1 or PM-AGP2. The more negatively charged fraction contained molecules with
      a glycosyl composition characteristic of AGPs and included at least two different
      macromolecules. The results of this investigation indicate that Rosa plasma
      membrane contains at least four distinct AGPs or AGP-like molecules. These
      molecules differed from each other in size, charge, hydrophobicity, amino-acyl
      composition, and/or protein content.

PMID- 12226445
TI  - The Role of Ligand Exchange in the Uptake of Iron from Microbial Siderophores by
      Gramineous Plants.
AB  - The siderophore rhizoferrin, produced by the fungus Rhizopus arrhizus, was
      previously found to be as an efficient Fe source as Fe-ethylenediamine-di(o
      hydroxphenylacetic acid) to strategy I plants. The role of this microbial
      siderophore in Fe uptake by strategy II plants is the focus of this research. Fe
      rhizoferrin was found to be an efficient Fe source for barley (Hordeum vulgare
      L.) and corn (Zea mays L.). The mechanisms by which these Gramineae utilize Fe
      from Fe-rhizoferrin and from other chelators were studied. Fe uptake from 59Fe
      rhizoferrin, 59Fe-ferrioxamine B, 59Fe-ethylenediaminetetraacetic acid, and 59Fe
      2[prime]-deoxymugineic acid by barley plants grown in nutrient solution at pH 6.0
      was examined during periods of high (morning) and low (evening) phytosiderophore
      release. Uptake and translocation rates from Fe chelates paralleled the diurnal
      rhythm of phytosiderophore release. In corn, however, similar uptake and
      translocation rates were observed both in the morning and in the evening. A
      constant rate of the phytosiderophore's release during 14 h of light was found in
      the corn cv Alice. The results presented support the hypothesis that Fe from Fe
      rhizoferrin is taken up by strategy II plants via an indirect mechanism that
      involves ligand exchange between the ferrated microbial siderophore and
      phytosiderophores, which are then taken up by the plant. This hypothesis was
      verified by in vitro ligand-exchange experiments.

PMID- 12226446
TI  - Partial Purification and Characterization of an Inducible Indole-3-Acetyl-L
      Aspartic Acid Hydrolase from Enterobacter agglomerans.
AB  - Indole-3-acetyl-amino acid conjugate hydrolases are believed to be important in
      the regulation of indole-3-acetic acid (IAA) metabolism in plants and therefore
      have potential uses for the alteration of plant IAA metabolism. To isolate
      bacterial strains exhibiting significant indole-3-acetyl-aspartate (IAA-Asp)
      hydrolase activity, a sewage sludge inoculation was cultured under conditions in
      which IAA-Asp served as the sole source of carbon and nitrogen. One isolate,
      Enterobacter agglomerans, showed hydrolase activity inducible by IAA-L-Asp or N
      acetyl-L-Asp but not by IAA, (NH4)2SO4, urea, or indoleacetamide. Among a total
      of 17 IAA conjugates tested as potential substrates, the enzyme had an
      exclusively high substrate specificity for IAA-L-Asp. Substrate concentration
      curves and Lineweaver-Burk plots of the kinetic data showed a Michaelis constant
      value for IAA-L-Asp of 13.5 mM. The optimal pH for this enzyme was between 8.0
      and 8.5. In extraction buffer containing 0.8 mM Mg2+ the hydrolase activity was
      inhibited to 80% by 1 mM dithiothreitol and to 60% by 1 mm CuSO4; the activity
      was increased by 40% with 1 mM MnSO4. However, in extraction buffer with no trace
      elements, the hydrolase activity was inhibited to 50% by either 1 mM
      dithiothreitol or 1% Triton X-100 (Sigma). These results suggest that disulfide
      bonding might be essential for enzyme activity. Purification of the hydrolase by
      hydroxyapatite and TSK-phenyl (HP-Genenchem, South San Francisco, CA) preparative
      high-performance liquid chromatography yielded a major 45-kD polypeptide as shown
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

PMID- 12226447
TI  - The Early Entry of Al into Cells of Intact Soybean Roots (A Comparison of Three
      Developmental Root Regions Using Secondary Ion Mass Spectrometry Imaging).
AB  - Al localization was compared in three developmental regions of primary root of an
      Al-sensitive soybean (Glycine max) genotype using secondary ion mass
      spectrometry. In cryosections obtained after a 4-h exposure to 38 [mu]M [Al3+],
      Al had penetrated across the root and into the stele in all three regions.
      Although the greatest localized Al concentration was consistently at the root
      periphery, the majority of the Al in each region had accumulated in cortical
      cells. It was apparent that the secondary ion mass spectrometry 27Al+ mass signal
      was spread throughout the intracellular area and was not particularly intense in
      the cell wall. Inclusion of some cell wall in determinations of the Al levels
      across the root radius necessitated that these serve as minimal estimates for
      intracellular Al. Total accumulation of intracellular Al for each region was 60,
      73, and 210 nmol g-1 fresh weight after 4 h, increasing with root development.
      Early metabolic responses to external Al, including those that have been reported
      deep inside the root and in mature regions, might result directly from
      intracellular Al. These responses might include ion transport events at the
      endodermis of mature roots or events associated with lateral root emergence, as
      well as events within the root tip.

PMID- 12226448
TI  - Oxidative Stress Results in Increased Sinks for Metabolic Energy during Aging and
      Sprouting of Potato Seed-Tubers.
AB  - Glutathione-mediated free-radical-scavenging and plasma membrane ATPase
      activities increase as sinks for metabolic energy with advancing tuber age.
      Plasma membrane ATPase activity from 19-month-old tubers was 77% higher than that
      from 7-month-old tubers throughout sprouting. The higher activity was not
      attended by an increase in the amount of ATPase per unit plasma membrane protein.
      Concentrations of oxidized (GSSG) and reduced glutathione more than doubled as
      tuber age advanced from 6 to 30 months, but the proportion of GSSG to total
      glutathione remained constant with age. The activity of glutathione transferase,
      an enzyme that catabolizes lipid-hydroperoxides, increased by 44 and 205% on a
      fresh weight and protein basis, respectively, as tubers aged from 6 to 30 months.
      Glutathione reductase activity also increased with advancing age, by 90% on a
      fresh weight basis and 305% on a protein basis. Older tubers had more glutathione
      reductase per unit of soluble and mitochondrial protein. The age-induced increase
      in cytosolic glutathione transferase activity was likely due to increased
      availability of lipid-hydroperoxides and/or a positive effector. Synthesis of
      glutathione requires ATP, and the increased reduction of GSSG resulting from
      catalysis of lipid-hydroperoxides is NADPH-dependent. Thus, increased plasma
      membrane ATPase and glutathione-mediated free-radical-scavenging activities
      likely constitute substantial sinks for ATP in older tubers prior to and during
      sprouting. Increased oxidative stress and loss in membrane integrity and central
      features of aging that undoubtedly contribute to the enhanced respiration of
      sprouting older tubers.

PMID- 12226449
TI  - Polyamine Accumulation and Near Loss of Morphogenesis in Long-Term Callus
      Cultures of Rice (Restoration of Plant Regeneration by Manipulation of Cellular
      Polyamine Levels).
AB  - We have shown (S. Bajaj and M.V. Rajam [1995] Plant Cell Rep 14: 717-720) that a
      significant reduction in morphogenetic potential occurs in callus cultures of
      rice (Oryza sativa L. cv TN-1) (up to 1 year old), and that plant regeneration
      could be improved in such cultures with spermidine treatment. We now show a near
      loss in plant regeneration capacity, concomitant with massive polyamine
      accumulation (primarily the diamine putrescine), due to the increase in arginine
      decarboxylase activity and an altered putrescine-to-spermidine ratio in 20- and
      36-month-old rice callus cultures. The blockage of polyamine accumulation due to
      the reduction in arginine decarboxylase activity by a putrescine synthesis
      inhibitor, [alpha]-difluoromethylarginine, completely restored plant regeneration
      capacity in these long-term cultures. Additionally, spermidine treatment of long
      term cultures caused an increase in cellular spermidine content and a reduction
      in putrescine content and arginine decarboxylase activity, leading to an
      adjustment in putrescine-to-spermidine ratio and the restoration of plant
      regeneration ability.

PMID- 12226450
TI  - Direct Inhibition of Plant Mitochondrial Respiration by Elevated CO2.
AB  - Doubling the concentration of atmospheric CO2 often inhibits plant respiration,
      but the mechanistic basis of this effect is unknown. We investigated the direct
      effects of increasing the concentration of CO2 by 360 [mu]L L-1 above ambient on
      O2 uptake in isolated mitochondria from soybean (Glycine max L. cv Ransom)
      cotyledons. Increasing the CO2 concentration inhibited the oxidation of
      succinate, external NADH, and succinate and external NADH combined. The
      inhibition was greater when mitochondria were preincubated for 10 min in the
      presence of the elevated CO2 concentration prior to the measurement of O2 uptake.
      Elevated CO2 concentration inhibited the salicylhydroxamic acid-resistant
      cytochrome pathway, but had no direct effect on the cyanide-resistant alternative
      pathway. We also investigated the direct effects of elevated CO2 concentration on
      the activities of cytochrome c oxidase and succinate dehydrogenase (SDH) and
      found that the activity of both enzymes was inhibited. The kinetics of inhibition
      of cytochrome c oxidase were time-dependent. The level of SDH inhibition depended
      on the concentration of succinate in the reaction mixture. Direct inhibition of
      respiration by elevated CO2 in plants and intact tissues may be due at least in
      part to the inhibition of cytochrome c oxidase and SDH.

PMID- 12226451
TI  - Purification of Mitochondrial Glutamate Dehydrogenase from Dark-Grown Soybean
      Seedlings.
AB  - Proteins in extracts from cotyledons, hypocotyls, and roots of 5-d-old, dark
      grown soybean (Glycine max L. Merr. cv Williams) seedlings were separated by
      polyacrylamide gel electrophoresis. Three isoforms of glutamate dehydrogenase
      (GDH) were resolved and visualized in gels stained for GDH activity. Two isoforms
      with high electrophoretic mobility, GDH1 and GDH2, were in protein extracts from
      cotyledons and a third isoform with the lowest electrophoretic mobility, GDH3,
      was identified in protein extracts from root and hypocotyls. Subcellular
      fractionation of dark-grown soybean tissues demonstrated that GDH3 was associated
      with intact mitochondria. GDH3 was purified to homogeneity, as determined by
      native and sodium dodecyl sulfate-polyacrylamide gels. The isoenzyme was composed
      of a single 42-kD subunit. The pH optima for the reductive amination and the
      oxidative deamination reactions were 8.0 and 9.3, respectively. At any given pH,
      GDH activity was 12- to 50-fold higher in the direction of reductive amination
      than in the direction of the oxidative deamination reaction. GDH3 had a cofactor
      preference for NAD(H) over NADP(H). The apparent Michaelis constant values for
      [alpha]-ketoglutarate, ammonium, and NADH at pH 8.0 were 3.6, 35.5, and 0.07 mM,
      respectively. The apparent Michaelis constant values for glutamate and NAD were
      15.8 and 0.10 mM at pH 9.3, respectively. To our knowledge, this is the first
      biochemical and physical characterization of a purified mitochondrial NAD(H)
      dependent GDH isoenzyme from soybean.

PMID- 12226452
TI  - Nitrite Transport in Chloroplast Inner Envelope Vesicles (I. Direct Measurement
      of Proton-Linked Transport).
AB  - Chloroplast inner envelope membrane vesicles that are loaded with the pH
      sensitive fluorophore, pyranine, show rapid internal acidification when nitrite
      is added. Acidification is dependent upon [delta]pH, with the inside of vesicles
      being alkaline with respect to the outside. The rate of vesicle acidification was
      directly proportional to the concentration of nitrite that was added and the
      imposed pH difference across the membrane. In contrast, added nitrate had no
      effect on vesicle acidification. Nitrite also caused acidification of asolectin
      vesicles. The extent of vesicle acidification is dependent on the internal volume
      of vesicles. Inner envelope and asolectin vesicles that were prepared by
      extrusion were approximately the same size, allowing them to be compared when the
      final extent of acidification, measured after the pH gradient had collapsed, was
      similar. The rate of nitrite-dependent acidification was similar in these two
      preparations at any single nitrite concentration. These results indicate that
      nitrite movement occurs by rapid diffusion across membranes as nitrous acid, and
      this movement is dependent on a proton gradient across the lipid bilayer. Under
      conditions approximating those in vivo, the rate of diffusion of nitrous acid far
      exceeds that of nitrite reduction within chloroplasts.

PMID- 12226453
TI  - 3,7-Dichloroquinolinecarboxylic Acid Inhibits Cell-Wall Biosynthesis in Maize
      Roots.
AB  - The mode of action of the herbicide 3,7-dichloroquinolinecar-boxylic acid
      (quinclorac) was examined by measuring incorporation of [14C]glucose,
      [14C]acetate, [3H]thymidine, and [3H]uridine into maize (Zea mays) root cell
      walls, fatty acids, DNA, and RNA, respectively. Among the precursors examined, 10
      [mu]M quinclorac inhibited [14C]glucose incorporation into the cell wall within 3
      h. Fatty acid and DNA biosynthesis were subsequently inhibited, whereas RNA
      biosynthesis was unaffected. In contrast to the cellulose synthesis inhibitor 2,6
      dichlorobenzonitrile, quinclorac strongly inhibited cellulose and a hemicellulose
      fraction presumed to be glucuronoarabinoxylan. However, the synthesis of (1
      >3),(1->4)-[beta]-D-glucans was only slightly inhibited. The degree of inhibition
      was time- and dose-dependent. By 4 h after treatment, the concentration that
      inhibited [14C]glucose incorporation into the cell wall, cellulose, and the
      sensitive hemicellulose fraction by 50% was about 15, 5, and 20 [mu]M,
      respectively. Concomitant with an inhibition of [14C]glucose incorporation into
      the cell wall, quinclorac treatment led to a marked accumulation of radioactivity
      in the cytosol. The increased radioactivity was found mostly in glucose and
      fructose. However, total levels of glucose, fructose, and uridine diphosphate
      glucose were not changed greatly by quinclorac. These data suggest that
      quinclorac acts primarily as a cell-wall biosynthesis inhibitor in a susceptible
      grass by a mechanism that is different from that of 2,6-dichlorobenzonitrile.

PMID- 12226454
TI  - Fucoid Zygotes Germinate from Their Darkest Regions, Not Their Brightest Ones.

PMID- 12226455
TI  - Chlorophyll Breakdown in Senescent Leaves.

PMID- 12226456
TI  - Maize Root Phytase (Purification, Characterization, and Localization of Enzyme
      Activity and Its Putative Substrate).
AB  - Three phytase (EC 3.1.3.26) isoforms from the roots of 8-d-old maize (Zea mays L.
      var Consul) seedlings were separated from phosphatases and purified to near
      homogeneity. The molecular mass of the native protein was 71 kD, and the
      isoelectric points of the three isoforms were pH 5.0, 4.9, and 4.8. Each of the
      three isoforms consisted of two subunits with a molecular mass of 38 kD. The
      temperature and pH optima (40[deg]C, pH 5.0) of these three isoforms, as well as
      the apparent Michaelis constants for sodium inositol hexakisphosphate (phytate)
      (43, 25, and 24 [mu]M) as determined by the release of inorganic phosphate, were
      only slightly different. Phytate concentrations higher than 300 [mu]M were
      inhibitory to all three isoforms. In contrast, the dephosphorylation of 4
      nitrophenyl phosphate was not inhibited by any substrate concentration, but the
      Michaelis constants for this substrate were considerably higher (137-157 [mu]M).
      Hydrolysis of phytate by the phytase isoforms is a nonrandom reaction. D/L
      Inositol-1,2,3,4,5- pentakisphosphate was identified as the first and D/L
      inositol-1,2,5,6-tetrakisphosphate as the second intermediate in phytate
      hydrolysis. Phytase activity was localized in root slices. Although phosphatase
      activity was present in the stele and the cortex of the primary root, phytase
      activity was confined to the endodermis. Phytate was identified as the putative
      native substrate in maize roots (45 [mu]g P g-1 dry matter). It was readily
      labeled upon supplying [32P]phosphate to the roots.

PMID- 12226457
TI  - Frequencies, Timing, and Spatial Patterns of Co-Suppression of Nitrate Reductase
      and Nitrite Reductase in Transgenic Tobacco Plants.
AB  - Frequencies, timing, and spatial patterns of co-suppression of the nitrate (Nia)
      and nitrite (Nii) genes were analyzed in transgenic tobacco (Nicotiana tabacum)
      plants carrying either Nia or Nii cDNAs under the control of the 35S promoter, or
      a Nii gene with its own regulatory signals (promoter, introns, and terminator)
      cloned downstream of two copies of the enhancer of the 35S promoter. We show that
      (a) the frequencies of transgenic lines affected by co- suppression are similar
      for the three constructs, ranging from 19 to 25%; (b) Nia and Nii co-suppression
      are triggered stochastically during a phenocritical period of 2 weeks between
      germination and flowering; (c) the timing of co-suppression (i.e. the percentage
      of isogenic plants affected by co-suppression reported as a function of the
      number of days of culture) differs from one transgenic line to another; (d) the
      percentage of isogenic plants affected by co-suppression is increased by growing
      the plants in vitro prior to their transfer to the greenhouse and to the field;
      and (e) at the end of the culture period, plants are either unaffected,
      completely co-suppressed, or variegated. Suppressed and nonsuppressed parts of
      these variegated plants are separated by a vertical plane through the stem in Nia
      co-suppression, and separated by a horizontal plane in Nii co-suppression.

PMID- 12226458
TI  - Accumulation of Al in Root Mucilage of an Al-Resistant and an Al-Sensitive
      Cultivar of Wheat.
AB  - To estimate rates of Al accumulation within the symplasm, all apoplastic pools of
      Al need to be eliminated or accounted for. We have developed a revised kinetic
      protocol that allows us to estimate the contribution of mucilage-bound Al to
      total, nonexchangeable Al, and to eliminate the mucilage as an apoplastic pool of
      Al. By comparing the Al content of excised root tips (2 cm) of wheat (Triticum
      aestivum L.) with and without the removal of the mucilage (using a 10-min wash in
      1 M NH4Cl), we found that Al bound to the mucilage accounted for approximately 25
      to 35% of Al remaining after desorption in citric acid. The kinetics of Al uptake
      into mucilage were biphasic, with a rapid phase occurring in the first 30 min of
      uptake, followed by a linear phase occurring in the remainder of the experimental
      period (180 min). By adopting a step for removal of mucilage into our existing
      kinetic protocol, we have been able to isolate a linear phase of uptake with only
      a slight deviation from linearity in the first 5 min. Although we cannot
      unambiguously identify this phase of uptake as uptake into the symplasm, we
      believe this new protocol provides us with the most accurate quantitative
      estimate of symplastic Al yet available.

PMID- 12226459
TI  - Red Xylem and Higher Lignin Extractability by Down-Regulating a Cinnamyl Alcohol
      Dehydrogenase in Poplar.
AB  - Cinnamyl alcohol dehydrogenase (CAD) catalyzes the last step in the biosynthesis
      of the lignin precursors, the monolignols. We have down-regulated CAD in
      transgenic poplar (Populus tremula X Populus alba) by both antisense and co
      suppression strategies. Several antisense and sense CAD transgenic poplars had an
      approximately 70% reduced CAD activity that was associated with a red coloration
      of the xylem tissue. Neither the lignin amount nor the lignin monomeric
      composition (syringyl/guaiacyl) were significantly modified. However,
      phloroglucinol-HCl staining was different in the down-regulated CAD plants,
      suggesting changes in the number of aldehyde units in the lignin. Furthermore,
      the reactivity of the cell wall toward alkali treatment was altered: a lower
      amount of lignin was found in the insoluble, saponified residue and more lignin
      could be precipitated from the soluble alkali fraction. Moreover, large amounts
      of phenolic compounds, vanillin and especially syringaldehyde, were detected in
      the soluble alkali fraction of the CAD down-regulated poplars. Alkaline pulping
      experiments on 3-month-old trees showed a reduction of the kappa number without
      affecting the degree of cellulose degradation. These results indicate that
      reducing the CAD activity in trees might be a valuable strategy to optimize
      certain processes of the wood industry, especially those of the pulp and paper
      industry.

PMID- 12226460
TI  - In Vitro Prenylation of the Small GTPase Rac13 of Cotton.
AB  - Previous work (D.P. Delmer, J. Pear, A. Andrawis, D. Stalker [1995] Mol Gen Genet
      248: 43-51) has identified a gene in cotton (Gossypium hirsutum), Rac13, that
      encodes a small, signal-transducing GTPase and shows high expression in the fiber
      at the time of transition from primary to secondary wall synthesis. Since Rac13
      may be important in signal transduction pathway(s), regulating the onset of fiber
      secondary wall synthesis, we continue to characterize Rac13 by determining its
      ability to undergo posttranslational modification. In animals Rac proteins
      contain the C-terminal consensus sequence CaaL (where "a" can be any aliphatic
      residue), which is a site for geranylgeranylation (B.T. Kinsella, R.A. Erdman,
      W.A. Maltese [1994] J Biol Chem 266: 9786-9794). We have identified activities in
      developing cotton fibers that resemble in specificity the geranylgeranyl- and
      farnesyltransferases of animals and yeast. In addition, using prenyltransferases
      from rabbit reticulocytes, we show that Rac13, having a C-terminal sequence of
      CAFL, can serve as an in vitro substrate for geranylgeranylation but not
      farnesylation. However, the presence of the uncommon penultimate F residue
      appears to slow the rate of prenylation considerably compared with other
      acceptors.

PMID- 12226461
TI  - Stimulation of Photophosphorylation by Ascorbate as a Function of Light
      Intensity.
AB  - When isolated, stroma-free thylakoids are illuminated in the presence of ADP and
      orthophosphate in the absence of any electron acceptor except O2, the addition of
      ascorbate stimulates electron transport through the formation of the radical
      monodehydroascorbate and the coupled synthesis of ATP (G. Forti and G. Elli
      [1995] Plant Physiol 109: 1207-1211). The stimulation is shown here to be higher
      at low light intensity. These observations are explained in terms of the increase
      of the electron transport rate by ascorbate, which established a higher value of
      the steady-state pH gradient, causing activation of ATP synthase, which is known
      to be dependent on the level of the H+-electrochemical potential difference, and
      a higher rate of proton flux across the membranes available for utilization by
      ATP synthesis.

PMID- 12226462
TI  - Regulation of the Expression of the Glycine Decarboxylase Complex during Pea Leaf
      Development.
AB  - The expression of the genes encoding the four proteins (P, H, T, and L) of
      glycine decarboxylase, a multienzymatic complex involved in the mitochondrial
      step of the photorespiration pathway, was examined during pea (Pisum sativum)
      leaf development in comparison with ribulose-1,5-bisphosphate
      carboxylase/oxygenase. Mitochondria from the primary leaf were isolated at
      several well-defined stages of development. Their capacity to oxidize glycine was
      negligible during the earlier stages but increased dramatically once the leaflet
      opened. This was correlated with the accumulation of the glycine decarboxylase
      complex (GDC) proteins, which was shown to occur in preexisting mitochondria,
      producing an increase in their density. The transcription of the GDC genes was
      coordinated and occurred early, with a peak at 7 d, a stage at which mitochondria
      are unable to oxidize glycine. This implies the existence of posttranscriptional
      control of gene expression. The comparison of the expression patterns of the
      genes encoding specific proteins of GDC with that of rbcS genes suggests a common
      regulation scheme that is related to light induction. However, ribulose-1,5
      bisphosphate carboxylase/oxygenase is present in the chloroplast well before GDC
      fills the mitochondria, suggesting that the setup of photorespiration occurs in
      cells already engaged in active photosynthesis.

PMID- 12226463
TI  - Changes in Calcium-Dependent Protein Kinase Activity during in Vitro Tuberization
      in Potato.
AB  - A soluble Ca2+-dependent protein kinase (CDPK) was purified to homogeneity in
      potato (Solanum tuberosum L.) plants. Potato CDPK was strictly dependent on Ca2+
      (one-half maximal activation 0.6 [mu]M) and phosphorylated a wide diversity of
      substrates, in which Syntide 2 was the best phosphate acceptor (Michaelis
      constant = 30 [mu]M). The kinase was inhibited by Ca2+-chelating agents,
      phenotiazine derivatives, and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide
      (one-half maximal inhibition = 0.25 mM). Polyclonal antibodies directed against
      the regulatory region of the soybean CDPK recognized a 53-kD polypeptide. In an
      autophosphorylation assay, this same band was strongly labeled with [[gamma]
      32P]ATP in the presence of Ca2+. CDPK activity was high in nontuberized plants,
      but increased 2.5-fold at the onset of tuber development and was reduced to one
      half of its original activity when the tuber had completed formation. In the
      early stages of tuberization, Ca2+-dependent phosphorylation of endogenous
      targets (specific bands of 68, 51, and 46 kD) was observed. These polypeptides
      were not labeled in nontuberizing plants or in completely formed tubers,
      indicating that this phosphorylation is a stage-specific event. In addition,
      dephosphorylation of specific polypeptides was detected in tuberizing plants,
      suggesting the involvement of a phosphatase. Preincubation of crude extracts with
      phosphatase inhibitors rendered a 100% increase in CDPK activity.

PMID- 12226464
TI  - Driving Forces for Bicarbonate Transport in the Cyanobacterium Synechococcus R-2
      (PCC 7942).
AB  - Air-grown Synechococcus R-2 (PCC 7942) cultures grown in BG-11 medium are very
      alkaline (outside pH is 10.0) and use HCO3- as their inorganic carbon source. The
      cells showed a dependence on Na+ for photosynthesis, but low Na+ conditions (1
      mol m-3) were sufficient to support saturating photosynthesis. The intracellular
      dissolved inorganic carbon in the light was greater than 20 mol m-3 in both low
      Na+ conditions and in BG-11 medium containing the usual [Na+] (24 mol m-3,
      designated high-Na+ conditions). The electrochemical potential for HCO3- in the
      light was in excess of 25 kJ mol-1, even in high-Na+ conditions. The Na+-motive
      force was greater than -12 kJ mol-1 under both Na+ conditions. On thermodynamic
      grounds, an Na+-driven co-port process would need to have a stoichiometry of 2 or
      greater ([greater than or equal to]2Na+ in/HCO3-1 in), but we show that Na+ or K+
      fluxes cannot be linked to HCO3- transport. Na+ and K+ fluxes were unaffected by
      the presence or absence of dissolved inorganic carbon. In low-Na+ conditions, Na+
      fluxes are too low to support the observed net 14C-carbon fixation rate. Active
      transport of HCO3- hyperpolarizes (not depolarizes) the membrane potential.

PMID- 12226465
TI  - Evidence for a UDP-Glucose Transporter in Golgi Apparatus-Derived Vesicles from
      Pea and Its Possible Role in Polysaccharide Biosynthesis.
AB  - The Golgi apparatus in plant cells is involved in hemicellulose and pectin
      biosynthesis. While it is known that glucan synthase I is responsible for the
      formation of [beta]-l-4-linked glucose (Glc) polymers and uses UDP-Glc as a
      substrate, very little is known about the topography of reactions leading to the
      biosynthesis of polysaccharides in this organelle. We isolated from pea (Pisum
      sativum) stems a fraction highly enriched in Golgi apparatus-derived vesicles
      that are sealed and have the same topographical orientation that the membranes
      have in vivo. Using these vesicles and UDP-Glc, we reconstituted polysaccharide
      biosynthesis in vitro and found evidence for a luminal location of the active
      site of glucan synthase I. In addition, we identified a UDP-Glc transport
      activity, which is likely to be involved in supplying substrate for glucan
      synthase I. We found that UDP-Glc transport is protein mediated. Moreover, our
      results suggest that UDP-Glc transport is coupled to the exit of a luminal
      uridine-containing nucleotide via an antiporter mechanism. We suggest that UDP
      Glc is transported into the lumen of Golgi and that Glc is transferred to a
      polysaccharide chain, whereas the nucleotide moiety leaves the vesicle by an
      antiporter mechanism.

PMID- 12226466
TI  - Characterization of Glutathione S-Transferase Isoforms in Three Maize Inbred
      Lines Exhibiting Differential Sensitivity to Alachlor.
AB  - Glutathione S-transferases (GSTs) are a family of isozymes that catalyze the
      conjugation of glutathione to several xenobiotics, including a number of
      important herbicides. Several GST isoforms have been identified in maize (Zea
      mays L.). In this study we focused on three isoforms, GST I, II, and IV, derived
      from homo-or heterodimerization of two subunits GST-29 and GST-27, which have
      been shown to be responsible for reactivity to alachlor. The expression of these
      isoforms was examined in three inbred lines of maize that showed tolerance,
      susceptibility, and intermediate resistance to alachlor (2-Cl-N-[2,6
      diethylphenyl]-N-[methoxymethyl]acetamide) treatment. The different isoforms were
      separated by anion-exchange chromatography and subunits were quantified by
      western blot analysis. GST assays were performed against both 1-Cl-2,4
      dinitrobenzene and alachlor. This analysis showed that the susceptible and
      intermediate lines exhibit impaired function in the GST-27 and GST-29 subunits,
      respectively. In addition, this study suggests that GST IV is the principal,
      detoxifying enzyme for alachlor, although GST I and II are required to achieve
      tolerance to high rates of the herbicide.

PMID- 12226467
TI  - The Physiological Relevance of Na+-Coupled K+-Transport.
AB  - Plant roots utilize at least two distinct pathways with high and low affinities
      to accumulate K+. The system for high-affinity K+ uptake, which takes place
      against the electrochemical K+ gradient, requires direct energization.
      Energization of K+ uptake via Na+ coupling has been observed in algae and was
      recently proposed as a mechanism for K+ uptake in wheat (Triticum aestivum L.).
      To investigate whether Na+ coupling has general physiological relevance in
      energizing K+ transport, we screened a number of species, including Arabidopsis
      thaliana L. Heynh. ecotype Columbia, wheat, and barley (Hordeum vulgare L.), for
      the presence of Na+-coupled K+ uptake. Rb+-flux analysis and electrophysiological
      K+-transport assays were performed in the presence and absence of Na+ and
      provided evidence for a coupling between K+ and Na+ transport in several aquatic
      species. However, all investigated terrestrial species were able to sustain
      growth and K+ uptake in the absence of Na+. Furthermore, the addition of Na+ was
      either without effect or inhibited K+ absorption. The latter characteristic was
      independent of growth conditions with respect to Na+ status and pH. Our results
      suggest that in terrestrial species Na+-coupled K+ transport has no or limited
      physiological relevance, whereas in certain aquatic angiosperms and algae this
      type of secondary transport energization plays a significant role.

PMID- 12226468
TI  - Overexpression of L-Phenylalanine Ammonia-Lyase in Transgenic Tobacco Plants
      Reveals Control Points for Flux into Phenylpropanoid Biosynthesis.
AB  - Transgenic tobacco (Nicotiana tabacum L.) plants overexpressing the enzyme L
      phenylalanine ammonia-lyase (PAL; EC 4.3.1.5) were grown from seeds of a primary
      transformant containing the bean PAL2 gene, which had shown homology-dependent
      silencing of the endogenous tobacco PAL genes. Analysis of endogenous and
      transgene-encoded PAL transcripts and protein in the primary transformant (T0)
      and first-generation (T1) overexpressor plants indicated that the transgene
      encoded PAL is the cause of the greater than wild-type levels of PAL activity (up
      to 5- and 2-fold greater in leaf and stem tissue, respectively) in the T1 plants.
      Leaves of PAL-overexpressing plants contained increased levels of the
      hydroxycinnamic acid ester chlorogenic acid but not of the flavonoid rutin,
      indicating that PAL is the key control point for flux into chlorogenic acid. In
      addition, levels of the glucoside of 4-coumaric acid increased in the
      overexpressing plants, suggesting that the 4-coumarate:coenzyme A ligase or
      coumarate hydroxylase reactions might have become limiting. These results help to
      define the regulatory architecture of the phenylpropanoid pathway and indicate
      the possibility of engineering-selective changes in this complex metabolic
      pathway by overexpression of a single early pathway gene.

PMID- 12226469
TI  - Acclimation of Foliar Antioxidant Systems to Growth Irradiance in Three Broad
      Leaved Evergreen Species.
AB  - The protective role of leaf antioxidant systems in the mechanism of plant
      acclimation to growth irradiance was studied in Vinca major, Schefflera
      arboricola, and Mahonia repens, which were grown for several months at 20, 100,
      and 1200 [mu]mol photons m-2 s-1. As growth irradiance increased, several
      constituents of the "Mehler-peroxidase" pathway also increased: superoxide
      dismutase, ascorbate peroxidase, glutathione reductase, ascorbate, and
      glutathione. This occurred concomitantly with increases in the xanthophyll cycle
      pool size and in the rate of nonphotochemical energy dissipation under steady
      state conditions. There was no evidence for photosystem II overreduction in
      plants grown at high irradiance, although the reduction state of the stromal NADP
      pool, estimated from measurements of NADP-malate dehydrogenase activity, was
      greater than 60% in V. major and S. arboricola. Ascorbate, which removes reactive
      O2 species generated by O2 photoreduction in the chloroplast and serves as a
      reductant for the conversion of the xanthophyll cycle pigments to the de
      epoxidized forms A plus Z, generally exhibited the most dramatic increases in
      response to growth irradiance. We conclude from these results that O2
      photoreduction occurs at higher rates in leaves acclimated to high irradiance,
      despite increases in xanthophyll cycle-dependent energy dissipation, and that
      increases in leaf antioxidants protect against this potential oxidative stress.

PMID- 12226470
TI  - Solubilization, Partial Purification, and Characterization of a Binding Site for
      a Glycopeptide Elicitor from Microsomal Membranes of Tomato Cells.
AB  - Purified glycopeptides derived from yeast invertase act as highly potent
      elicitors in suspension-cultured tomato (Lycopersicon esculentum [L.] Mill)
      cells, inducing ethylene biosynthesis and phenylalanine ammonia lyase half
      maximally at concentrations of 1 to 5 nM. We previously demonstrated the presence
      of a high-affinity binding site that specifically recognized these glycopeptides
      in cells and microsomal membranes of tomato (C.W. Basse, A. Fath, T. Boller
      [1993] J Biol Chem 268: 14724-14731). This elicitor-binding site was solubilized
      in an active form from the microsomal membranes using the neutral detergents n
      dodecylmaltoside and n-dodecanoylsucrose and purified 67-fold in a single step by
      anion-exchange chromatography. Ligand saturation studies and competition
      experiments with unlabeled glycopeptides and glycans demonstrated that the
      detergent-solubilized elicitor-binding site retained the high affinity (Kd
      approximately 1-4 nM) and selectivity of the membrane-bound form. The binding
      site was found to have a high affinity for N-linked glycans with nine mannosyl
      residues from fungal glycoproteins, whereas it did not recognize the typical
      mammalian glycans with nine mannosyl residues, demonstrating further its high
      selectivity.

PMID- 12226471
TI  - Ethylene Biosynthesis during Aerenchyma Formation in Roots of Maize Subjected to
      Mechanical Impedance and Hypoxia.
AB  - Germinated maize (Zea mays L.) seedlings were enclosed in modified triaxial cells
      in an artificial substrate and exposed to oxygen deficiency stress (4% oxygen,
      hypoxia) or to mechanical resistance to elongation growth (mechanical impedance)
      achieved by external pressure on the artificial substrate, or to both hypoxia and
      impedance simultaneously. Compared with controls, seedlings that received either
      hypoxia or mechanical impedance exhibited increased rates of ethylene evolution,
      greater activities of 1-aminocyclopropane-1-carboxylic acid (ACC) synthase, ACC
      oxidase, and cellulase, and more cell death and aerenchyma formation in the root
      cortex. Effects of hypoxia plus mechanical impedance were strongly synergistic on
      ethylene evolution and ACC synthase activity; cellulase activity, ACC oxidase
      activity, or aerenchyma formation did not exhibit this synergism. In addition,
      the lag between the onset of stress and increases in both ACC synthase activity
      and ethylene production was shortened by 2 to 3 h when mechanical impedance or
      impedance plus hypoxia was applied compared with hypoxia alone. The synergistic
      effects of hypoxia and mechanical impedance and the earlier responses to
      mechanical impedance than to hypoxia suggest that different mechanisms are
      involved in the promotive effects of these stresses on maize root ethylene
      biosynthesis.

PMID- 12226472
TI  - An Ethylene-Mediated Increase in Sensitivity to Auxin Induces Adventitious Root
      Formation in Flooded Rumex palustris Sm.
AB  - The hormonal regulation of adventitious root formation induced by flooding of the
      root system was investigated in the wetland species Rumex palustris Sm.
      Adventitious root development at the base of the shoot is an important adaptation
      to flooded conditions and takes place soon after the onset of flooding. Decreases
      in either endogenous auxin or ethylene concentrations induced by application of
      inhibitors of either auxin transport or ethylene biosynthesis reduced the number
      of adventitious roots formed by flooded plants, suggesting an involvement of
      these hormones in the rooting process. The rooting response during flooding was
      preceded by increased endogenous ethylene concentrations in the root system. The
      endogenous auxin concentration did not change during flooding-induced rooting,
      but a continuous basipetal transport of auxin from the shoot to the rooting zone
      appeared to be essential in maintaining stable auxin concentrations. These
      results suggest that the higher ethylene concentration in soil-flooded plants
      increases the sensitivity of the root-forming tissues to endogenous indoleacetic
      acid, thus initiating the formation of adventitious roots.

PMID- 12226473
TI  - Physiological Characterization of Root Zn2+ Absorption and Translocation to
      Shoots in Zn Hyperaccumulator and Nonaccumulator Species of Thlaspi.
AB  - Radiotracer techniques were employed to characterize 65Zn2+ influx into the root
      symplasm and translocation to the shoot in Thlaspi caerulescens, a Zn
      hyperaccumulator, and Thlaspi arvense, a nonaccumulator. A protocol was developed
      that allowed us to quantify unidirectional 65Zn2+ influx across the root-cell
      plasma membrane (20 min of radioactive uptake followed by 15 min of desorption in
      a 100 [mu]M ZnCl2 + 5 mM CaCl2 solution). Concentration-dependent Zn2+ influx in
      both Thlaspi species yielded nonsaturating kinetic curves that could be resolved
      into linear and saturable components. The linear kinetic component was shown to
      be cell-wall-bound Zn2+ remaining in the root after desorption, and the saturable
      component was due to Zn2+ influx across the root-cell plasma membrane. This
      saturable component followed Michaelis-Menten kinetics, with similar apparent
      Michaelis constant values for T. caerulescens and T. arvense (8 and 6 [mu]M,
      respectively). However, the maximum initial velocity for Zn2+ influx in T.
      caerulescens root cells was 4.5-fold higher than for T. arvense, indicating that
      enhanced absorption into the root is one of the mechanisms involved in Zn
      hyperaccumulation. After 96 h 10-fold more 65Zn was translocated to the shoot of
      T. caerulescens compared with T. arvense. This indicates that transport sites
      other than entry into the root symplasm are also stimulated in T. caerulescens.
      We suggest that although increased root Zn2+ influx is a significant component,
      transport across the plasma membrane and tonoplast of leaf cells must also be
      critical sites for Zn hyperaccumulation in T. caerulescens.

PMID- 12226474
TI  - Total Glutamine Synthetase Activity during Soybean Nodule Development Is
      Controlled at the Level of Transcription and Holoprotein Turnover.
AB  - Gln synthetase (GS) catalyzes the ATP-dependent condensation of ammonia with
      glutamate to yield Gln. In higher plants GS is an octameric enzyme and the
      subunits are encoded by members of a small multigene family. In soybeans (Glycine
      max), following the onset of N2 fixation there is a dramatic increase in GS
      activity in the root nodules. GS activity staining of native polyacrylamide gels
      containing nodule and root extracts showed a common band of activity (GSrs). The
      nodules also contained a slower-migrating, broad band of enzyme activity (GSns).
      The GSns activity band is a complex of many isozymes made up of different
      proportions of two kinds of GS subunits: GSr and GSn. Root nodules formed
      following inoculation with an Nif- strain of Bradyrhizobium japonicum showed the
      presence of GS isoenzymes (GSns1) with low enzyme activity, which migrated more
      slowly than GSns. Gsns1 is most likely made up predominantly of GSn subunits. Our
      data suggest that, whereas the class I GS genes encoding the GSr subunits are
      regulated by the availability of NH3, the class II GS genes coding for the GSn
      subunits are developmentally regulated. Furthermore, we have demonstrated that
      the GSns1 isozymes in the Nif- nodules are relatively more labile. Our overall
      conclusion is that GSns activity in soybean nodules is regulated by N2 fixation
      both at the level of transcription and at the level of holoprotein stability.

PMID- 12226478
TI  - Protein nitration is mediated by heme and free metals through Fenton-type
      chemistry: an alternative to the NO/O2- reaction.
AB  - The chemical origins of nitrated tyrosine residues (NT) formed in proteins during
      a variety of pathophysiological conditions remain controversial. Although
      numerous studies have concluded that NT is a signature for peroxynitrite (ONOO(
      )) formation, other works suggest the primary involvement of peroxidases. Because
      metal homeostasis is often disrupted in conditions bearing NT, the role of metals
      as catalysts for protein nitration was examined. Cogeneration of nitric oxide
      (NO) and superoxide (O(2)(-)), from spermine/NO (2.7 microM/min) and xanthine
      oxidase (1-28 microM O(2)(-)/min), respectively, resulted in protein nitration
      only when these species were produced at approximately equivalent rates. Addition
      of ferriprotoporphyrin IX (hemin) to this system increased nitration over a broad
      range of O(2)(-) concentrations with respect to NO. Nitration in the presence of
      superoxide dismutase but not catalase suggested that ONOO(-) might not be
      obligatory to this process. Hemin-mediated NT formation required only the
      presence of NO(2)(-) and H(2)O(2), which are stable end-products of NO and O(2)(
      ) degradation. Ferrous, ferric, and cupric ions were also effective catalysts,
      indicating that nitration is mediated by species capable of Fenton-type
      chemistry. Although ONOO(-) can nitrate proteins, there are severe spatial and
      temporal constraints on this reaction. In contrast, accumulation of metals and
      NO(2)(-) subsequent to NO synthase activity can result in far less discriminate
      nitration in the presence of an H(2)O(2) source. Metal catalyzed nitration may
      account for the observed specificity of protein nitration seen under pathological
      conditions, suggesting a major role for translocated metals and the labilization
      of heme in NT formation.

PMID- 12226481
TI  - Short RNAs can identify new candidate transposable element families in
      Arabidopsis.

PMID- 12226482
TI  - Evidence for a plastid origin of plant ethylene receptor genes.

PMID- 12226479
TI  - Hypoxia and acidosis activate cardiac myocyte death through the Bcl-2 family
      protein BNIP3.
AB  - Coronary artery disease leads to injury and loss of myocardial tissue by
      deprivation of blood flow (ischemia) and is a major underlying cause of heart
      failure. Prolonged ischemia causes necrosis and apoptosis of cardiac myocytes and
      vascular cells; however, the mechanisms of ischemia-mediated cell death are
      poorly understood. Ischemia is associated with both hypoxia and acidosis due to
      increased glycolysis and lactic acid production. We recently reported that
      hypoxia does not induce cardiac myocyte apoptosis in the absence of acidosis. We
      now report that hypoxia-acidosis-associated cell death is mediated by BNIP3, a
      member of the Bcl-2 family of apoptosis-regulating proteins. Chronic hypoxia
      induced the expression and accumulation of BNIP3 mRNA and protein in cardiac
      myocytes, but acidosis was required to activate the death pathway. Acidosis
      stabilized BNIP3 protein and increased the association with mitochondria. Cell
      death by hypoxia-acidosis was blocked by pretreatment with antisense BNIP3
      oligonucleotides. The pathway included extensive DNA fragmentation and opening of
      the mitochondrial permeability transition pore, but no apparent caspase
      activation. Overexpression of wild-type BNIP3, but not a translocation-defective
      mutant, activated cardiac myocyte death only when the myocytes were acidic. This
      pathway may figure significantly in muscle loss during myocardial ischemia.

PMID- 12226483
TI  - Plant lipoxygenases. Physiological and molecular features.

PMID- 12226475
TI  - A molecular profile of a hematopoietic stem cell niche.
AB  - The hematopoietic microenvironment provides a complex molecular milieu that
      regulates the self-renewal and differentiation activities of stem cells. We have
      characterized a stem cell supportive stromal cell line, AFT024, that was derived
      from murine fetal liver. Highly purified in vivo transplantable mouse stem cells
      are maintained in AFT024 cultures at input levels, whereas other primitive
      progenitors are expanded. In addition, human stem cells are very effectively
      supported by AFT024. We suggest that the AFT024 cell line represents a component
      of an in vivo stem cell niche. To determine the molecular signals elaborated in
      this niche, we undertook a functional genomics approach that combines extensive
      sequence mining of a subtracted cDNA library, high-density array hybridization
      and in-depth bioinformatic analyses. The data have been assembled into a
      biological process oriented database, and represent a molecular profile of a
      candidate stem cell niche.

PMID- 12226484
TI  - Inositol phospholipid metabolism in Arabidopsis. Characterized and putative
      isoforms of inositol phospholipid kinase and phosphoinositide-specific
      phospholipase C.
AB  - Phosphoinositides (PIs) constitute a minor fraction of total cellular lipids in
      all eukaryotic cells. They fulfill many important functions through interaction
      with a wide range of cellular proteins. Members of distinct inositol lipid kinase
      families catalyze the synthesis of these phospholipids from phosphatidylinositol.
      The hydrolysis of PIs involves phosphatases and isoforms of PI-specific
      phospholipase C. Although our knowledge of the roles played by plant PIs is
      clearly limited at present, there is no doubt that they are involved in many
      physiological processes during plant growth and development. In this review, we
      concentrate on inositol lipid-metabolizing enzymes from the model plant
      Arabidopsis for which biochemical characterization data are available, namely the
      inositol lipid kinases and PI-specific phospholipase Cs. The biochemical
      properties and structure of characterized and genome-predicted isoforms are
      presented and compared with those of the animal enzymes to show that the plant
      enzymes have some features clearly unique to this kingdom.

PMID- 12226485
TI  - Cell-specific expression of homospermidine synthase, the entry enzyme of the
      pyrrolizidine alkaloid pathway in Senecio vernalis, in comparison with its
      ancestor, deoxyhypusine synthase.
AB  - Pyrrolizidine alkaloids (PAs) are constitutive plant defense compounds with a
      sporadic taxonomic occurrence. The first committed step in PA biosynthesis is
      catalyzed by homospermidine synthase (HSS). Recent evidence confirmed that HSS
      evolved by gene duplication from deoxyhypusine synthase (DHS), an enzyme involved
      in the posttranslational activation of the eukaryotic translation initiation
      factor 5A. To better understand the evolutionary relationship between these two
      enzymes, which are involved in completely different biological processes, we
      studied their tissue-specific expression. RNA-blot analysis, reverse
      transcriptase-PCR, and immunolocalization techniques demonstrated that DHS is
      constitutively expressed in shoots and roots of Senecio vernalis (Asteraceae),
      whereas HSS expression is root specific and restricted to distinct groups of
      endodermis and neighboring cortex cells located opposite to the phloem. All
      efforts to detect DHS by immunolocalization failed, but studies with promoter
      beta-glucuronidase fusions confirmed a general expression pattern, at least in
      young seedlings of tobacco (Nicotiana tabacum). The expression pattern for HSS
      differs completely from its ancestor DHS due to the adaptation of HSS to the
      specific requirements of PA biosynthesis.

PMID- 12226486
TI  - Differential expression of a metallothionein gene during the presymbiotic versus
      the symbiotic phase of an arbuscular mycorrhizal fungus.
AB  - A full-length cDNA encoding a metallothionein (MT)-like polypeptide, designated
      GmarMT1, was identified in an expressed sequence tag collection from germinated
      spores of the arbuscular mycorrhizal fungus Gigaspora margarita (BEG34). The
      GmarMT1 gene is composed of two exons separated by an 81-bp intron. It codes for
      a 65-amino acid polypeptide comprising a plant type 1 MT-like N-terminal domain
      and a C-terminal domain that is most closely related to an as-yet-uncharacterized
      fungal MT. As revealed by heterologous complementation assays in yeast, GmarMT1
      encodes a functional polypeptide capable of conferring increased tolerance
      against Cd and Cu. The GmarMT1 RNA is expressed in both presymbiotic spores and
      symbiotic mycelia, even in the absence of metal exposure, but is significantly
      less abundant in the latter stage. An opposite pattern was observed upon Cu
      exposure, which up-regulated GmarMT1 expression in symbiotic mycelia but not in
      germinated spores. Together, these data provide the first evidence, to our
      knowledge, for the occurrence in an arbuscular mycorrhizal fungus of a
      structurally novel MT that is modulated in a metal and life cycle stage-dependent
      manner and may afford protection against heavy metals (and other types of stress)
      to both partners of the endomycorrhizal symbiosis.

PMID- 12226487
TI  - VFL, the grapevine FLORICAULA/LEAFY ortholog, is expressed in meristematic
      regions independently of their fate.
AB  - The flowering process in grapevine (Vitis vinifera) takes place in buds and
      extends for two consecutive growing seasons. To understand the genetic and
      molecular mechanisms underlying this process, we have characterized grapevine bud
      development, cloned the grapevine FLORICAULA/LEAFY (FLO/LFY) ortholog, VFL, and
      analyzed its expression patterns during vegetative and reproductive development.
      Flowering induction takes place during the first season. Upon induction, the
      shoot apical meristem begins to produce lateral meristems that will give rise to
      either inflorescences or tendrils. During the second season, after a winter
      dormancy period, buds reactivate and inflorescence meristems give rise to flower
      meristems. VFL is expressed in lateral meristems that give rise to inflorescence
      and flower meristems, consistent with a role in reproductive development.
      Furthermore, VFL is also detected in other meristematic regions such as the
      vegetative shoot apical meristem and the lateral meristems that will give rise to
      tendrils. VFL is also expressed in leaf primordia and in growing leaf margins
      until later stages of development. Accumulation of VFL transcripts in cell
      proliferating regions suggests a role for VFL not only in flower meristem
      specification, but also in the maintenance of indeterminacy before the
      differentiation of derivatives of the apical meristem: flowers, leaves, or
      tendrils.

PMID- 12226488
TI  - Effect of regulated overexpression of the MADS domain factor AGL15 on flower
      senescence and fruit maturation.
AB  - We have examined the effect of regulated overexpression of AGL15, a member of the
      MADS domain family of regulatory factors, on reproductive tissues. Using
      molecular and physiological markers, we show that constitutive overexpression of
      AGL15 in Arabidopsis leads to delay and down-regulation of senescence programs in
      perianth organs and developing fruits and alters the process of seed desiccation.
      Through genetic crosses, we show that the rate of water loss in the maturing
      seeds is dictated by the genetic composition and physiological state of the
      maternal tissue, rather than the embryo. To define the developmental time and/or
      place when senescence programs are most affected by elevated AGL15 levels, we
      expressed AGL15 under the control of various promoters. Expression during
      senescence or in abscission zone cells did not produce delays in floral organ
      senescence or abscission. Using a glucocorticoid-inducible expression system, we
      show that an increase in AGL15 levels around the time of flower opening is
      necessary to delay senescence and increase floral organ longevity.

PMID- 12226489
TI  - Molecular identification of cytosolic, patatin-related phospholipases A from
      Arabidopsis with potential functions in plant signal transduction.
AB  - Rapid activation of phospholipase A (PLA) by auxin or plant-pathogen interaction
      suggests a function in signal transduction for this enzyme, but the molecular
      identification of a cytosolic PLA carrying out this function remains open. We
      isolated four cDNA sequences from Arabidopsis (ecotype Columbia), AtPLA I, AtPLA
      IIA, AtPLA IVA, and AtPLA IVC, which are members of the patatin-related PLA gene
      family in plants and which are homologous to the animal Ca(2+)-independent PLA(2)
      gene family. Expression was measured by reverse transcriptase-polymerase chain
      reaction, and AtPLA I transcripts were found preferentially in shoots, AtPLA IIA
      and AtPLA IVA in roots, and AtPLA IVC in flowers. Transient expression of the
      four PLA-green fluorescent protein fusion proteins in tobacco (Nicotiana tabacum)
      leaves showed they were located in the cytosol and not in the vacuoles.
      Surprisingly, AtPLA::green fluorescent protein was also localized to
      chloroplasts. The enzymatic activity of the purified recombinant AtPLA IVA toward
      phosphatidylcholine was dependent on Ca(2+), saturated at 0.5 mM, and had a pH
      optimum of about 7.0. It had both PLA(1) and PLA(2) specificity. The enzyme
      showed in vitro highest sensitivity toward the PLA(2) inhibitors
      palmitoyltrifluoromethyl ketone (PACOCF(3), K(i) approximately 30 nM),
      arachidonyltrifluoromethyl ketone (AACOCF(3), K(i) approximately 25 microM), and
      tetrahydro-3-(1-naphtalenyl)-2H-pyran-2-one (K(i) approximately 200 nM) and was
      also sensitive to other previously used inhibitors 5,8,11,14-eicosatetraynoic
      acid (K(i) approximately 3 microM) and nordihydroguajaretic acid (K(i)
      approximately 15 microM). The influence of these PLA(2) inhibitors on elongation
      in etiolated Arabidopsis seedlings was tested, and tetrahydro-3-(1-naphtalenyl)
      2H-pyran-2-one and 5,8,11,14-eicosatetraynoic acid inhibited hypocotyl elongation
      maximally at concentrations close to their K(i) in vitro.

PMID- 12226490
TI  - The circadian clock that controls gene expression in Arabidopsis is tissue
      specific.
AB  - The expression of CHALCONE SYNTHASE (CHS) expression is an important control step
      in the biosynthesis of flavonoids, which are major photoprotectants in plants.
      CHS transcription is regulated by endogenous programs and in response to
      environmental signals. Luciferase reporter gene fusions showed that the CHS
      promoter is controlled by the circadian clock both in roots and in aerial organs
      of transgenic Arabidopsis plants. The period of rhythmic CHS expression differs
      from the previously described rhythm of chlorophyll a/b-binding protein (CAB)
      gene expression, indicating that CHS is controlled by a distinct circadian clock.
      The difference in period is maintained in the wild-type Arabidopsis accessions
      tested and in the de-etiolated 1 and timing of CAB expression 1 mutants. These
      clock-affecting mutations alter the rhythms of both CAB and CHS markers,
      indicating that a similar (if not identical) circadian clock mechanism controls
      these rhythms. The distinct tissue distribution of CAB and CHS expression
      suggests that the properties of the circadian clock differ among plant tissues.
      Several animal organs also exhibit heterogeneous circadian properties in culture
      but are believed to be synchronized in vivo. The fact that differing periods are
      manifest in intact plants supports our proposal that spatially separated copies
      of the plant circadian clock are at most weakly coupled, if not functionally
      independent. This autonomy has apparently permitted tissue-specific
      specialization of circadian timing.

PMID- 12226491
TI  - A role for the DOF transcription factor BPBF in the regulation of gibberellin
      responsive genes in barley aleurone.
AB  - Functional analyses of a number of hydrolase gene promoters, induced by
      gibberellin (GA) in aleurone cells following germination, have identified a GA
      responsive complex as a tripartite element containing a pyrimidine box motif 5'
      CCTTTT-3'. We describe here that BPBF, a barley (Hordeum vulgare) transcription
      factor of the DOF (DNA-Binding with One Finger) class, previously shown to be an
      activator of reserve protein encoding genes during development, also has a role
      in the control of hydrolase genes following seed germination. Northern-blot,
      reverse transcriptase-polymerase chain reaction, and in situ hybridization
      analyses evidenced that the transcripts of the BPBF-encoding gene (Pbf), besides
      being present during endosperm development, are also expressed in aleurone cells
      of germinated seeds where they are induced by GA, an effect counteracted by
      abscisic acid. Electrophoretic mobility shift assays have shown that the BPBF
      protein binds specifically to the pyrimidine box motif in vitro within the
      different sequence contexts that naturally occur in the promoters of genes
      encoding a cathepsin B-like protease (Al21) and a low-isoelectric point alpha
      amylase (Amy2/32b), both induced in the aleurone layers in response to GA. In
      transient expression experiments, BPBF repressed transcription of the Al21
      promoter in GA-treated barley aleurone layers and reverted the GAMYB-mediated
      activation of this protease promoter.

PMID- 12226492
TI  - A strobilurin fungicide enhances the resistance of tobacco against tobacco mosaic
      virus and Pseudomonas syringae pv tabaci.
AB  - The strobilurin class of fungicides comprises a variety of synthetic plant
      protecting compounds with broad-spectrum antifungal activity. In the present
      study, we demonstrate that a strobilurin fungicide, F 500 (Pyraclostrobin),
      enhances the resistance of tobacco (Nicotiana tabacum cv Xanthi nc) against
      infection by either tobacco mosaic virus (TMV) or the wildfire pathogen
      Pseudomonas syringae pv tabaci. F 500 was also active at enhancing TMV resistance
      in NahG transgenic tobacco plants unable to accumulate significant amounts of the
      endogenous inducer of enhanced disease resistance, salicylic acid (SA). This
      finding suggests that F 500 enhances TMV resistance in tobacco either by acting
      downstream of SA in the SA signaling mechanism or by functioning independently of
      SA. The latter assumption is the more likely because in infiltrated leaves, F 500
      did not cause the accumulation of SA-inducible pathogenesis-related (PR)-1
      proteins that often are used as conventional molecular markers for SA-induced
      disease resistance. However, accumulation of PR-1 proteins and the associated
      activation of the PR-1 genes were elicited upon TMV infection of tobacco leaves
      and both these responses were induced more rapidly in F 500-pretreated plants
      than in the water-pretreated controls. Taken together, our results suggest that F
      500, in addition to exerting direct antifungal activity, may also protect plants
      by priming them for potentiated activation of subsequently pathogen-induced
      cellular defense responses.

PMID- 12226493
TI  - An endoplasmic reticulum-bound Ca(2+)/Mn(2+) pump, ECA1, supports plant growth
      and confers tolerance to Mn(2+) stress.
AB  - Plants can grow in soils containing highly variable amounts of mineral nutrients,
      like Ca(2+) and Mn(2+), though the mechanisms of adaptation are poorly
      understood. Here, we report the first genetic study to determine in vivo
      functions of a Ca(2+) pump in plants. Homozygous mutants of Arabidopsis harboring
      a T-DNA disruption in ECA1 showed a 4-fold reduction in endoplasmic reticulum
      type calcium pump activity. Surprisingly, the phenotype of mutant plants was
      indistinguishable from wild type when grown on standard nutrient medium
      containing 1.5 mM Ca(2+) and 50 microM Mn(2+). However, mutants grew poorly on
      medium with low Ca(2+) (0.2 mM) or high Mn(2+) (0.5 mM). On high Mn(2+), the
      mutants failed to elongate their root hairs, suggesting impairment in tip growth
      processes. Expression of the wild-type gene (CAMV35S::ECA1) reversed these
      conditional phenotypes. The activity of ECA1 was examined by expression in a
      yeast (Saccharomyces cerevisiae) mutant, K616, which harbors a deletion of its
      endogenous calcium pumps. In vitro assays demonstrated that Ca(2+), Mn(2+), and
      Zn(2+) stimulated formation of a phosphoenzyme intermediate, consistent with the
      translocation of these ions by the pump. ECA1 provided increased tolerance of
      yeast mutant to toxic levels of Mn(2+) (1 mM) and Zn(2+)(3 mM), consistent with
      removal of these ions from the cytoplasm. These results show that despite the
      potential redundancy of multiple Ca(2+) pumps and Ca(2+)/H(+) antiporters in
      Arabidopsis, pumping of Ca(2+) and Mn(2+) by ECA1 into the endoplasmic reticulum
      is required to support plant growth under conditions of Ca(2+) deficiency or
      Mn(2+) toxicity.

PMID- 12226494
TI  - Movement of potato spindle tuber viroid reveals regulatory points of phloem
      mediated RNA traffic.
AB  - Increasing evidence indicates that the phloem mediates traffic of selective RNAs
      within a plant. How an RNA enters, moves in, and exits the phloem is poorly
      understood. Potato spindle tuber viroid (PSTVd) is a pathogenic RNA that does not
      encode proteins and is not encapsidated, and yet it replicates autonomously and
      traffics systemically within an infected plant. The viroid RNA genome must
      interact directly with cellular factors to accomplish these functions and is,
      therefore, an excellent probe to study mechanisms that regulate RNA traffic. Our
      analyses of PSTVd traffic in Nicotiana benthamiana yielded evidence that PSTVd
      movement within sieve tubes does not simply follow mass flow from source to sink
      organs. Rather, this RNA is transported into selective sink organs. Furthermore,
      two PSTVd mutants can enter the phloem to spread systemically but cannot exit the
      phloem in systemic leaves of tobacco (Nicotiana tabacum). A viroid most likely
      has evolved structural motifs that mimic endogenous plant RNA motifs so that they
      are recognized by cellular factors for traffic. Thus, analysis of PSTVd traffic
      functions may provide insights about endogenous mechanisms that control phloem
      entry, transport, and exit of RNAs.

PMID- 12226495
TI  - The bifunctional LKR/SDH locus of plants also encodes a highly active
      monofunctional lysine-ketoglutarate reductase using a polyadenylation signal
      located within an intron.
AB  - Both plants and animals catabolize lysine (Lys) via two consecutive enzymes, Lys
      ketoglutarate reductase (LKR) and saccharopine dehydrogenase (SDH), which are
      linked on a single polypeptide encoded by a single LKR/SDH gene. We have
      previously shown that the Arabidopsis LKR/SDH gene also encodes a monofunctional
      SDH that is transcribed from an internal promoter. In the present report, we have
      identified two cDNAs derived from cotton (Gossypium hirsutum) boll abscission
      zone that encode a novel enzymatic form of Lys catabolism, i.e. a catabolic
      monofunctional LKR. The monofunctional LKR mRNA is also encoded by the LKR/SDH
      gene, using two weak polyadenylation sites located within an intron. In situ mRNA
      hybridization and quantitative reverse transcriptase-polymerase chain reaction
      analyses also suggest that the cotton monofunctional LKR is relatively abundantly
      expressed in parenchyma cells of the abscission zone. DNA sequence analysis of
      the LKR/SDH genes of Arabidopsis, maize (Zea mays), and tomato (Lycopersicon
      esculentum) suggests that these genes can also encode a monofunctional LKR mRNA
      by a similar mechanism. To test whether the LKR/SDH and monofunctional LKR
      enzymes possess different biochemical properties, we used recombinant Arabidopsis
      LKR/SDH and monofunctional LKR enzymes expressed in yeast (Saccharomyces
      cerevisiae) cells. The K(m) of the monofunctional LKR to Lys was nearly 10-fold
      lower than its counterpart that is linked to SDH. Taken together, our results
      suggest that the LKR/SDH locus of plants is a super-composite locus that can
      encode three related but distinct enzymes of Lys catabolism. These three enzymes
      apparently operate in concert to finely regulate Lys catabolism during plant
      development.

PMID- 12226496
TI  - Elongated mesocotyl1, a phytochrome-deficient mutant of maize.
AB  - To begin the functional dissection of light signal transduction pathways of maize
      (Zea mays), we have identified and characterized the light-sensing mutant elm1
      (elongated mesocotyl1). Seedlings homozygous for elm1 are pale green, show
      pronounced elongation of the mesocotyl, and fail to de-etiolate under red or far
      red light. Etiolated elm1 mutants contain no spectrally active phytochrome and do
      not deplete levels of phytochrome A after red-light treatment. High-performance
      liquid chromatography analyses show that elm1 mutants are unable to convert
      biliverdin IX alpha to 3Z-phytochromobilin, preventing synthesis of the
      phytochrome chromophore. Despite the impairment of the phytochrome
      photoreceptors, elm1 mutants can be grown to maturity in the field. Mature plants
      retain aspects of the seedling phenotype and flower earlier than wild-type plants
      under long days. Thus, the elm1 mutant of maize provides the first direct
      evidence for phytochrome-mediated modulation of flowering time in this
      agronomically important species.

PMID- 12226497
TI  - Isolation and characterization of a novel ribosome-inactivating protein from root
      cultures of pokeweed and its mechanism of secretion from roots.
AB  - Ribosome-inactivating proteins are N-glycosidases that remove a specific adenine
      from the sarcin/ricin loop of the large rRNA, thus arresting protein synthesis at
      the translocation step. In the present study, a novel type I ribosome
      inactivating protein, termed PAP-H, was purified from Agrobacterium rhizogenes
      transformed hairy roots of pokeweed (Phytolacca americana). The protein was
      purified by anion- and cation-exchange chromatography. PAP-H has a molecular mass
      of 29.5 kD as detected by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, and its isoelectric point was determined to be 7.8. Yeast
      (Saccharomyces cerevisiae) ribosomes incubated with PAP-H released the 360
      nucleotide diagnostic fragment from the 26S rRNA upon aniline treatment, an
      indication of its ribosome-inactivating activity. Using immunofluorescence
      microscopy, PAP-H was found to be located in the cell walls of hairy roots and
      root border cells. PAP-H was determined to be constitutively secreted as part of
      the root exudates, with its secretion enhanced by a mechanism mediated by
      ethylene induction. Purified PAP-H did not show in vitro antifungal activity
      against soil-borne fungi. In contrast, root exudates containing PAP-H as well as
      additional chitinase, beta-1,3-glucanase, and protease activities did inhibit the
      growth of soil-borne fungi. We found that PAP-H depurinates fungal ribosomes in
      vitro and in vivo, suggesting an additive mechanism that enables PAP-H to
      penetrate fungal cells.

PMID- 12226498
TI  - Engineering herbicide metabolism in tobacco and Arabidopsis with CYP76B1, a
      cytochrome P450 enzyme from Jerusalem artichoke.
AB  - The Jerusalem artichoke (Helianthus tuberosus) xenobiotic inducible cytochrome
      P450, CYP76B1, catalyzes rapid oxidative dealkylation of various phenylurea
      herbicides to yield nonphytotoxic metabolites. We have found that increased
      herbicide metabolism and tolerance can be achieved by ectopic constitutive
      expression of CYP76B1 in tobacco (Nicotiana tabacum) and Arabidopsis.
      Transformation with CYP76B1 conferred on tobacco and Arabidopsis a 20-fold
      increase in tolerance to linuron, a compound detoxified by a single dealkylation,
      and a 10-fold increase in tolerance to isoproturon or chlortoluron, which need
      successive catalytic steps for detoxification. Two constructs for expression of
      translational fusions of CYP76B1 with P450 reductase were prepared to test if
      they would yield even greater herbicide tolerance. Plants expressing these
      constructs had lower herbicide tolerance than CYP76B1 alone, which is apparently
      a consequence of reduced stability of the fusion proteins. In all cases,
      increased herbicide tolerance results from more extensive metabolism, as
      demonstrated with exogenously fed phenylurea. Beside increased herbicide
      tolerance, expression of CYP76B1 has no other visible phenotype in the transgenic
      plants. Our data indicate that CYP76B1 can function as a selectable marker for
      plant transformation, allowing efficient selection in vitro and in soil-grown
      plants. Plants expressing CYP76B1 may also be a potential tool for
      phytoremediation of contaminated sites.

PMID- 12226499
TI  - The altered pattern of amylose accumulation in the endosperm of low-amylose
      barley cultivars is attributable to a single mutant allele of granule-bound
      starch synthase I with a deletion in the 5'-non-coding region.
AB  - Reasons for the variable amylose content of endosperm starch from waxy cultivars
      of barley (Hordeum vulgare) were investigated. The mature grains of most such
      cultivars contain some amylose, although amounts are much lower than in wild-type
      cultivars. In these low-amylose cultivars, amylose synthesis starts relatively
      late in grain development. Starch granules in the outer cell layers of the
      endosperm contain more amylose than those in the center. This distribution
      corresponds to that of granule-bound starch synthase I (GBSSI), which is more
      severely reduced in amount in the center of the endosperm than in the outer cell
      layers, relative to wild-type cultivars. A second GBSSI in the barley plant,
      GBSSIb, is not detectable in the endosperm and cannot account for amylose
      synthesis in the low-amylose cultivars. The change in the expression of GBSSI in
      the endosperm of the low-amylose cultivars appears to be due to a 413-bp deletion
      of part of the promoter and 5'-untranslated region of the gene. Although these
      cultivars are of diverse geographical origin, all carry this same deletion,
      suggesting that the low-amylose cultivars have a common waxy ancestor. Records
      suggest a probable source in China, first recorded in the 16th century. Two
      further families of waxy cultivars have no detectable amylose in the endosperm
      starch. These amylose-free cultivars were selected in the 20th century from
      chemically mutagenized populations of wild-type barley. In both cases, 1-bp
      alterations in the GBSSI gene completely eliminate GBSSI activity.

PMID- 12226500
TI  - Indole acetic acid distribution coincides with vascular differentiation pattern
      during Arabidopsis leaf ontogeny.
AB  - We used an anti-indole acetic acid (IAA or auxin) monoclonal antibody-based
      immunocytochemical procedure to monitor IAA level in Arabidopsis tissues. Using
      immunocytochemistry and the IAA-driven beta-glucuronidase (GUS) activity of
      Aux/IAA promoter::GUS constructs to detect IAA distribution, we investigated the
      role of polar auxin transport in vascular differentiation during leaf development
      in Arabidopsis. We found that shoot apical cells contain high levels of IAA and
      that IAA decreases as leaf primordia expand. However, seedlings grown in the
      presence of IAA transport inhibitors showed very low IAA signal in the shoot
      apical meristem (SAM) and the youngest pair of leaf primordia. Older leaf
      primordia accumulate IAA in the leaf tip in the presence or absence of IAA
      transport inhibition. We propose that the IAA in the SAM and the youngest pair of
      leaf primordia is transported from outside sources, perhaps the cotyledons, which
      accumulate more IAA in the presence than in the absence of transport inhibition.
      The temporal and spatial pattern of IAA localization in the shoot apex indicates
      a change in IAA source during leaf ontogeny that would influence flow direction
      and, consequently, the direction of vascular differentiation. The IAA production
      and transport pattern suggested by our results could explain the venation
      pattern, and the vascular hypertrophy caused by IAA transport inhibition. An
      outside IAA source for the SAM supports the notion that IAA transport and
      procambium differentiation dictate phyllotaxy and organogenesis.

PMID- 12226501
TI  - Arabidopsis CYP98A3 mediating aromatic 3-hydroxylation. Developmental regulation
      of the gene, and expression in yeast.
AB  - The general phenylpropanoid pathways generate a wide array of aromatic secondary
      metabolites that range from monolignols, which are ubiquitous in all plants, to
      sinapine, which is confined to crucifer seeds. The biosynthesis of these
      compounds involves hydroxylated and methoxylated cinnamyl acid, aldehyde, or
      alcohol intermediates. Of the three enzymes originally proposed to hydroxylate
      the 4-, 3-, and 5-positions of the aromatic ring, cinnamate 4-hydroxylase (C4H),
      which converts trans-cinnamic acid to p-coumaric acid, is the best characterized
      and is also the archetypal plant P450 monooxygenase. Ferulic acid 5-hydroxylase
      (F5H), a P450 that catalyzes 5-hydroxylation, has also been studied, but the
      presumptive 3-hydroxylase converting p-coumarate to caffeate has been elusive. We
      have found that Arabidopsis CYP98A3, also a P450, could hydroxylate p-coumaric
      acid to caffeic acid in vivo when expressed in yeast (Saccharomyces cerevisiae)
      cells, albeit very slowly. CYP98A3 transcript was found in Arabidopsis stem and
      silique, resembling both C4H and F5H in this respect. CYP98A3 showed further
      resemblance to C4H in being highly active in root, but differed from F5H in this
      regard. In transgenic Arabidopsis, the promoters of CYP98A3 and C4H showed wound
      inducibility and a comparable developmental regulation throughout the life cycle,
      except in seeds, where the CYP98A3 promoter construct was inactive while
      remaining active in silique walls. Within stem and root tissue, the gene product
      and the promoter activity of CYP98A3 were most abundant in lignifying cells.
      Collectively, these studies show involvement of CYP98A3 in the general
      phenylpropanoid metabolism, and suggest a downstream function for CYP98A3
      relative to the broader and upstream role of C4H.

PMID- 12226502
TI  - Regulated expression of Arabidopsis phosphate transporters.
AB  - Phosphorus deficiency is one of the major abiotic stresses affecting plant
      growth. Plants respond to the persistent deficiency of phosphate (Pi) by
      coordinating the expression of genes involved in alleviation of the stress. The
      high-affinity Pi transporters are among the major molecular determinants that are
      activated during Pi stress. In this study, using three reporter genes (green
      fluorescent protein, luciferase, and beta-glucuronidase) regulated by two Pi
      transporter promoters, we have carried out an extensive analysis of
      transcriptional and spatial regulation of gene expression. Activation of the
      genes was rapid, repressible, and specific in response to changes in Pi
      availability. The phytohormones auxin and cytokinin suppressed the expression of
      the reporter gene driven by the AtPT1 promoter, and that of the native gene,
      suggesting that hormones may be involved in regulation of some component(s) of Pi
      starvation response pathway. These studies also provide molecular evidence for a
      potential role of high-affinity Pi transporters in mobilizing Pi into
      reproductive organs. The results suggest that members of the Pi transporter
      family may have similar but nonredundant functions in plants.

PMID- 12226503
TI  - Arabidopsis UVR8 regulates ultraviolet-B signal transduction and tolerance and
      contains sequence similarity to human regulator of chromatin condensation 1.
AB  - To further our understanding of how plants defend against the harmful effects of
      ultraviolet (UV) light, we characterized an Arabidopsis mutant hypersensitive to
      UV-B. This mutant, UV resistance locus 8-1 (uvr8-1), contains a single recessive
      mutation at the bottom of chromosome 5. Fine-scale mapping localized uvr8-1 to a
      21-kb locus containing five predicted open reading frames. Sequencing of this
      entire region revealed that the uvr8-1 allele contains a 15-nucleotide deletion
      in a gene similar to the human guanine nucleotide exchange factor regulator of
      chromatin condensation 1. This mutation reduces the UV-B-mediated induction of
      flavonoids and blocks chalcone synthase mRNA and protein induction. In contrast,
      uvr8-1 has enhanced induction of PR1 and PR5 proteins in response to UV-B, an
      indication of increased UV-B injury. These results suggest that UVR8 acts in a UV
      B signal transduction pathway leading to induction of flavonoid biosynthesis.

PMID- 12226504
TI  - Glycerophosphocholine metabolism in higher plant cells. Evidence of a new
      glyceryl-phosphodiester phosphodiesterase.
AB  - Glycerophosphocholine (GroPCho) is a diester that accumulates in different
      physiological processes leading to phospholipid remodeling. However, very little
      is known about its metabolism in higher plant cells. (31)P-Nuclear magnetic
      resonance spectroscopy and biochemical analyses performed on carrot (Daucus
      carota) cells fed with GroPCho revealed the existence of an extracellular GroPCho
      phosphodiesterase. This enzymatic activity splits GroPCho into sn-glycerol-3
      phosphate and free choline. In vivo, sn-glycerol-3-phosphate is further
      hydrolyzed into glycerol and inorganic phosphate by acid phosphatase. We
      visualized the incorporation and the compartmentation of choline and observed
      that the major choline pool was phosphorylated and accumulated in the cytosol,
      whereas a minor fraction was incorporated in the vacuole as free choline.
      Isolation of plasma membranes, culture medium, and cell wall proteins enabled us
      to localize this phosphodiesterase activity on the cell wall. We also report the
      existence of an intracellular glycerophosphodiesterase. This second activity is
      localized in the vacuole and hydrolyzes GroPCho in a similar fashion to the cell
      wall phosphodiesterase. Both extra- and intracellular phosphodiesterases are
      widespread among different plant species and are often enhanced during phosphate
      deprivation. Finally, competition experiments on the extracellular
      phosphodiesterase suggested a specificity for glycerophosphodiesters (apparent
      K(m) of 50 microM), which distinguishes it from other phosphodiesterases
      previously described in the literature.

PMID- 12226505
TI  - Biochemical characterization of the Arabidopsis protein kinase SOS2 that
      functions in salt tolerance.
AB  - The Arabidopsis Salt Overly Sensitive 2 (SOS2) gene encodes a serine/threonine
      (Thr) protein kinase that has been shown to be a critical component of the salt
      stress signaling pathway. SOS2 contains a sucrose-non-fermenting protein kinase
      1/AMP-activated protein kinase-like N-terminal catalytic domain with an
      activation loop and a unique C-terminal regulatory domain with an FISL motif that
      binds to the calcium sensor Salt Overly Sensitive 3. In this study, we examined
      some of the biochemical properties of the SOS2 in vitro. To determine its
      biochemical properties, we expressed and isolated a number of active and inactive
      SOS2 mutants as glutathione S-transferase fusion proteins in Escherichia coli.
      Three constitutively active mutants, SOS2T168D, SOS2T168D Delta F, and SOS2T168D
      Delta 308, were obtained previously, which contain either the Thr-168 to aspartic
      acid (Asp) mutation in the activation loop or combine the activation loop
      mutation with removal of the FISL motif or the entire regulatory domain. These
      active mutants exhibited a preference for Mn(2+) relative to Mg(2+) and could not
      use GTP as phosphate donor for either substrate phosphorylation or
      autophosphorylation. The three enzymes had similar peptide substrate specificity
      and catalytic efficiency. Salt overly sensitive 3 had little effect on the
      activity of the activation loop mutant SOS2T168D, either in the presence or
      absence of calcium. The active mutant SOS2T168D Delta 308 could not
      transphosphorylate an inactive protein (SOS2K40N), which indicates an
      intramolecular reaction mechanism of SOS2 autophosphorylation. Interestingly,
      SOS2 could be activated not only by the Thr-168 to Asp mutation but also by a
      serine-156 or tyrosine-175 to Asp mutation within the activation loop. Our
      results provide insights into the regulation and biochemical properties of SOS2
      and the SOS2 subfamily of protein kinases.

PMID- 12226506
TI  - Plasmalemma abscisic acid perception leads to RAB18 expression via phospholipase
      D activation in Arabidopsis suspension cells.
AB  - Abscisic acid (ABA) plays a key role in the control of stomatal aperture by
      regulating ion channel activities and water exchanges across the plasma membrane
      of guard cells. Changes in cytoplasmic calcium content and activation of anion
      and outward-rectifying K(+) channels are among the earliest cellular responses to
      ABA in guard cells. In Arabidopsis suspension cells, we have demonstrated that
      outer plasmalemma perception of ABA triggered similar early events. Furthermore,
      a Ca(2+) influx and the activation of anion channels are part of the ABA
      signaling pathway leading to the specific expression of RAB18. Here, we determine
      whether phospholipases are involved in ABA-induced RAB18 expression.
      Phospholipase C is not implicated in this ABA pathway. Using a
      transphosphatidylation reaction, we show that ABA plasmalemma perception results
      in a transient stimulation of phospholipase D (PLD) activity, which is necessary
      for RAB18 expression. Further experiments showed that PLD activation was unlikely
      to be regulated by heterotrimeric G proteins. We also observed that ABA-dependent
      stimulation of PLD was necessary for the activation of plasma anion current.
      However, when ABA activation of plasma anion channels was inhibited, the ABA
      dependent activation of PLD was unchanged. Thus, we conclude that in Arabidopsis
      suspension cells, ABA stimulation of PLD acts upstream from anion channels in the
      transduction pathway leading to RAB18 expression.

PMID- 12226507
TI  - Characterization of a novel lipoxygenase-independent senescence mechanism in
      Alstroemeria peruviana floral tissue.
AB  - The role of lipoxygenase (lox) in senescence of Alstroemeria peruviana flowers
      was investigated using a combination of in vitro assays and chemical profiling of
      the lipid oxidation products generated. Phospholipids and galactolipids were
      extensively degraded during senescence in both sepals and petals and the ratio of
      saturated/unsaturated fatty acids increased. Lox protein levels and enzymatic
      activity declined markedly after flower opening. Stereochemical analysis of lox
      products showed that 13-lox was the major activity present in both floral tissues
      and high levels of 13-keto fatty acids were also synthesized. Lipid
      hydroperoxides accumulated in sepals, but not in petals, and sepals also had a
      higher chlorophyll to carotenoid ratio that favors photooxidation of lipids. Loss
      of membrane semipermeability was coincident for both tissue types and was
      chronologically separated from lox activity that had declined by over 80% at the
      onset of electrolyte leakage. Thus, loss of membrane function was not related to
      lox activity or accumulation of lipid hydroperoxides per se and differs in these
      respects from other ethylene-insensitive floral tissues representing a novel
      pattern of flower senescence.

PMID- 12226508
TI  - Mitochondrial-driven bicarbonate transport supports photosynthesis in a marine
      microalga.
AB  - The CO(2)-concentrating mechanism (CCM) of the marine eustigmatophycean microalga
      Nannochloropsis gaditana consists of an active HCO(3)(-) transport system and an
      internal carbonic anhydrase to facilitate accumulation and conversion of HCO(3)(
      ) to CO(2) for photosynthetic fixation. Aqueous inlet mass spectrometry revealed
      that a portion of the CO(2) generated within the cells leaked to the medium,
      resulting in a significant rise in the extracellular CO(2) concentration to a
      level above its chemical equilibrium that was diagnostic for active HCO(3)(-)
      transport. The transient rise in extracellular CO(2) occurred in the light and
      the dark and was resolved from concurrent respiratory CO(2) efflux using
      H(13)CO(3)(-) stable isotope techniques. H(13)CO(3)(-) pump-(13)CO(2) leak
      activity of the CCM was unaffected by 10 microM 3(3,4-dichlorophenyl)-1,1
      dimethylurea, an inhibitor of chloroplast linear electron transport, although
      photosynthetic O(2) evolution was reduced by 90%. However, low concentrations of
      cyanide, azide, and rotenone along with anoxia significantly reduced or abolished
      (13)CO(2) efflux in the dark and light. These results indicate that H(13)CO(3)(-)
      transport was supported by mitochondrial energy production in contrast to other
      algae and cyanobacteria in which it is supported by photosynthetic electron
      transport. This is the first report of a direct role for mitochondria in the
      energization and functioning of the CCM in a photosynthetic organism.

PMID- 12226509
TI  - Early embryo development in Fucus distichus is auxin sensitive.
AB  - Auxin and polar auxin transport have been implicated in controlling embryo
      development in land plants. The goal of these studies was to determine if auxin
      and auxin transport are also important during the earliest stages of development
      in embryos of the brown alga Fucus distichus. Indole-3-acetic acid (IAA) was
      identified in F. distichus embryos and mature tissues by gas chromatography-mass
      spectroscopy. F. distichus embryos accumulate [(3)H]IAA and an inhibitor of IAA
      efflux, naphthylphthalamic acid (NPA), elevates IAA accumulation, suggesting the
      presence of an auxin efflux protein complex similar to that found in land plants.
      F. distichus embryos normally develop with a single unbranched rhizoid, but
      growth on IAA leads to formation of multiple rhizoids and growth on NPA leads to
      formation of embryos with branched rhizoids, at concentrations that are active in
      auxin accumulation assays. The effects of IAA and NPA are complete before 6 h
      after fertilization (AF), which is before rhizoid germination and cell division.
      The maximal effects of IAA and NPA are between 3.5 and 5 h AF and 4 and 5.5 h AF,
      respectively. Although, the location of the planes of cell division was
      significantly altered in NPA- and IAA-treated embryos, these abnormal divisions
      occurred after abnormal rhizoid initiation and branching was observed. The
      results of this study suggest that auxin acts in the formation of apical basal
      patterns in F. distichus embryo development.

PMID- 12226510
TI  - Sterol C-24 methyltransferase type 1 controls the flux of carbon into sterol
      biosynthesis in tobacco seed.
AB  - The first committed step in the conversion of cycloartenol into Delta(5) C24
      alkyl sterols in plants is catalyzed by an S-adenosyl-methionine-dependent sterol
      C24-methyltransferase type 1 (SMT1). We report the consequences of overexpressing
      SMT1 in tobacco (Nicotiana tabacum), under control of either the constitutive
      carnation etched ring virus promoter or the seed-specific Brassica napus acyl
      carrier protein promoter, on sterol biosynthesis in seed tissue. Overexpression
      of SMT1 with either promoter increased the amount of total sterols in seed tissue
      by up to 44%. The sterol composition was also perturbed with levels of sitosterol
      increased by up to 50% and levels of isofucosterol and campesterol increased by
      up to 80%, whereas levels of cycloartenol and cholesterol were decreased by up to
      53% and 34%, respectively. Concomitant with the enhanced SMT1 activity was an
      increase in endogenous 3-hydroxy-3-methylglutaryl coenzyme A reductase activity,
      from which one can speculate that reduced levels of cycloartenol feed back to up
      regulate 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and thereby
      control the carbon flux into sterol biosynthesis. This potential regulatory role
      of SMT1 in seed sterol biosynthesis is discussed.

PMID- 12226511
TI  - Two new loci, PLEIADE and HYADE, implicate organ-specific regulation of
      cytokinesis in Arabidopsis.
AB  - In screens for regulators of root morphogenesis in Arabidopsis we isolated six
      new recessive mutants with irregular cell expansion. Complementation analyses
      placed the mutations in two loci, PLEIADE (PLE) and HYADE (HYA). Phenotypic
      analyses revealed multinucleated cells, cell wall stubs, and synchronized cell
      divisions in incompletely separated cells that are all characteristics of
      defective cytokinesis. These defects were pronounced in roots and undetectable in
      aerial organs. In addition, fertility and germination were not affected by the
      mutations. Thus, the alleles that we have isolated of PLE and HYA suggest that
      the genes may encode organ-specific components needed primarily during root
      development. Analysis of microtubule arrays during cell cycle in ple and hya
      roots indicates that the presence of several synchronized nuclei influences the
      position of preprophase band, mitotic spindles, and phragmoplasts. The enhanced
      and synergistic phenotype of PLE/ple.hya/hya seedlings and double mutants point
      to a role of PLE and HYA in the same process. These mutants provide tools to
      elucidate the regulation of nuclear cytoskeletal interactions during cell
      division and cytokinesis.

PMID- 12226512
TI  - Light-intensity-dependent expression of Lhc gene family encoding light-harvesting
      chlorophyll-a/b proteins of photosystem II in Chlamydomonas reinhardtii.
AB  - Excessive light conditions repressed the levels of mRNAs accumulation of multiple
      Lhc genes encoding light-harvesting chlorophyll-a/b (LHC) proteins of photosystem
      (PS)II in the unicellular green alga, Chlamydomonas reinhardtii. The light
      intensity required for the repression tended to decrease with lowering
      temperature or CO(2) concentration. The responses of six LhcII genes encoding the
      major LHC (LHCII) proteins and two genes (Lhcb4 and Lhcb5) encoding the minor LHC
      proteins of PSII (CP29 and CP26) were similar. The results indicate that the
      expression of these Lhc genes is coordinately repressed when the energy input
      through the antenna systems exceeds the requirement for CO(2) assimilation. The
      Lhc mRNA level repressed under high-light conditions was partially recovered by
      adding the electron transport inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea,
      suggesting that redox signaling via photosynthetic electron carriers is involved
      in the gene regulation. However, the mRNA level was still considerably lower
      under high-light than under low-light conditions even in the presence of 3-(3,4
      dichlorophenyl)-1,1-dimethylurea. Repression of the Lhc genes by high light was
      prominent even in the mutants deficient in the reaction center(s) of PSII or both
      PSI and PSII. The results indicate that two alternative processes are involved in
      the repression of Lhc genes under high-light conditions, one of which is
      independent of the photosynthetic reaction centers and electron transport events.

PMID- 12226513
TI  - Inhibition of squalene synthase and squalene epoxidase in tobacco cells triggers
      an up-regulation of 3-hydroxy-3-methylglutaryl coenzyme a reductase.
AB  - To get some insight into the regulatory mechanisms controlling the sterol branch
      of the mevalonate pathway, tobacco (Nicotiana tabacum cv Bright Yellow-2) cell
      suspensions were treated with squalestatin-1 and terbinafine, two specific
      inhibitors of squalene synthase (SQS) and squalene epoxidase, respectively. These
      two enzymes catalyze the first two steps involved in sterol biosynthesis. In
      highly dividing cells, SQS was actively expressed concomitantly with 3-hydroxy-3
      methylglutaryl coenzyme A reductase and both sterol methyltransferases. At
      nanomolar concentrations, squalestatin was found to inhibit efficiently sterol
      biosynthesis as attested by the rapid decrease in SQS activity and
      [(14)C]radioactivity from acetate incorporated into sterols. A parallel dose
      dependent accumulation of farnesol, the dephosphorylated form of the SQS
      substrate, was observed without affecting farnesyl diphosphate synthase steady
      state mRNA levels. Treatment of tobacco cells with terbinafine is also shown to
      inhibit sterol synthesis. In addition, this inhibitor induced an impressive
      accumulation of squalene and a dose-dependent stimulation of the triacylglycerol
      content and synthesis, suggesting the occurrence of regulatory relationships
      between sterol and triacylglycerol biosynthetic pathways. We demonstrate that
      squalene was stored in cytosolic lipid particles, but could be redirected toward
      sterol synthesis if required. Inhibition of either SQS or squalene epoxidase was
      found to trigger a severalfold increase in enzyme activity of 3-hydroxy-3
      methylglutaryl coenzyme A reductase, giving first evidence for a positive
      feedback regulation of this key enzyme in response to a selective depletion of
      endogenous sterols. At the same time, no compensatory responses mediated by SQS
      were observed, in sharp contrast to the situation in mammalian cells.

PMID- 12226514
TI  - Probing in vivo metabolism by stable isotope labeling of storage lipids and
      proteins in developing Brassica napus embryos.
AB  - Developing embryos of Brassica napus accumulate both triacylglycerols and
      proteins as major storage reserves. To evaluate metabolic fluxes during embryo
      development, we have established conditions for stable isotope labeling of
      cultured embryos under steady-state conditions. Sucrose supplied via the
      endosperm is considered to be the main carbon and energy source for seed
      metabolism. However, in addition to 220 to 270 mM carbohydrates (sucrose,
      glucose, and fructose), analysis of endosperm liquid revealed up to 70 mM amino
      acids as well as 6 to 15 mM malic acid. Therefore, a labeling approach with
      multiple carbon sources is a precondition to quantitatively reflect fluxes of
      central carbon metabolism in developing embryos. Mid-cotyledon stage B. napus
      embryos were dissected from plants and cultured for 15 d on a complex liquid
      medium containing (13)C-labeled carbohydrates. The (13)C enrichment of fatty
      acids and amino acids (after hydrolysis of the seed proteins) was determined by
      gas chromatography/mass spectrometry. Analysis of (13)C isotope isomers of
      labeled fatty acids and plastid-derived amino acids indicated that direct
      glycolysis provides at least 90% of precursors of plastid acetyl-coenzyme A
      (CoA). Unlabeled amino acids, when added to the growth medium, did not reduce
      incorporation of (13)C label into plastid-formed fatty acids, but substantially
      diluted (13)C label in seed protein. Approximately 30% of carbon in seed protein
      was derived from exogenous amino acids and as a consequence, the use of amino
      acids as a carbon source may have significant influence on the total carbon and
      energy balance in seed metabolism. (13)C label in the terminal acetate units of
      C(20) and C(22) fatty acids that derive from cytosolic acetyl-CoA was also
      significantly diluted by unlabeled amino acids. We conclude that cytosolic acetyl
      CoA has a more complex biogenetic origin than plastidic acetyl-CoA. Malic acid in
      the growth medium did not dilute (13)C label incorporation into fatty acids or
      proteins and can be ruled out as a source of carbon for the major storage
      components of B. napus embryos.

PMID- 12226515
TI  - Tandemly duplicated Safener-induced glutathione S-transferase genes from Triticum
      tauschii contribute to genome- and organ-specific expression in hexaploid wheat.
AB  - Glutathione S-transferase (GST) gene expression was examined in several Triticum
      species, differing in genome constitution and ploidy level, to determine genome
      contribution to GST expression in cultivated, hexaploid bread wheat (Triticum
      aestivum). Two tandemly duplicated tau class GST genes (TtGSTU1 and TtGSTU2) were
      isolated from a single bacterial artificial chromosome clone in a library
      constructed from the diploid wheat and D genome progenitor to cultivated wheat,
      Triticum tauschii. The genes are very similar in genomic structure and their
      encoded proteins are 95% identical. Gene-specific reverse transcriptase
      polymerase chain reaction analysis revealed differential transcript accumulation
      of TtGSTU1 and TtGSTU2 in roots and shoots. Expression of both genes was induced
      by herbicide safeners, 2,4-dichlorophenoxyacetic acid and abscisic acid, in the
      shoots of T. tauschii; however, expression of TtGSTU1 was always higher than
      TtGSTU2. In untreated seedlings, TtGSTU1 was expressed in both shoots and roots,
      whereas TtGSTU2 expression was only detected in roots. RNA gel-blot analysis of
      ditelosomic, aneuploid lines that are deficient for 6AS, 6BS, or 6DS chromosome
      arms of cultivated, hexaploid bread wheat showed differential genome contribution
      to safener-induced GST expression in shoots compared with roots. The GST genes
      from the D genome of hexaploid wheat contribute most to safener-induced
      expression in the shoots, whereas GSTs from the B and D genomes contribute to
      safener-induced expression in the roots.

PMID- 12226516
TI  - Successive glycosyltransfer activity and enzymatic characterization of pectic
      polygalacturonate 4-alpha-galacturonosyltransferase solubilized from pollen tubes
      of Petunia axillaris using pyridylaminated oligogalacturonates as substrates.
AB  - Polygalacturonate 4-alpha-galacturonosyltransferase (pectin synthase) was
      solubilized from pollen tubes of Petunia axillaris and characterized. To
      accomplish this, an assay method using fluorogenic pyridylaminated
      oligogalacturonic acids (PA-OGAs) as acceptor substrates was developed. When the
      pollen tube enzyme was solubilized with 0.5% (v/v) Triton X-100 and was incubated
      with PA-OGA and UDP-galacturonic acid (UDP-GalUA), successive transfer activity
      of more than 10 GalUAs from UDP-GalUA to the nonreducing end of PA-OGA was
      observed by diethylaminoethyl high-performance liquid chromatography. This
      activity was time- and enzyme concentration-dependent. The optimum enzyme
      activity was observed at pH 7.0 and 30 degrees C. Among the PA-OGAs investigated,
      those with a degree of polymerization of more than 10 were preferred as
      substrates. The crude pollen tube enzyme had an apparent K(m) value of 13 microM
      for the PA-OGA with a degree of polymerization 11 and 170 microM for UDP-GalUA.
      The characteristics of the P. axillaris pollen tube enzyme and the usefulness of
      fluorogenic PA-OGAs for the assay of this enzyme are discussed.

PMID- 12226517
TI  - Developmentally regulated dual-specificity kinase from peanut that is induced by
      abiotic stresses.
AB  - Tyrosine (Tyr) phosphorylation represents an important biochemical mechanism to
      regulate many cellular processes. No Tyr kinase has been cloned so far in plants.
      Dual-specificity kinases are reported in plants and the function of these kinases
      remains unknown. A 1.7-kb cDNA that encodes serine/threonine/Tyr (STY) kinase was
      isolated by screening peanut (Arachis hypogaea) expression library using the anti
      phospho-Tyr antibody. The histidine-tagged recombinant kinase histidine-6-STY
      predominantly autophosphorylated on Tyr and phosphorylated the histone primarily
      on threonine. Genomic DNA gel-blot analysis revealed that STY kinase is a member
      of a small multigene family. The transcript of STY kinase is accumulated in the
      mid-maturation stage of seed development, suggesting a role in the signaling of
      storage of seed reserves. The STY kinase mRNA expression, as well as kinase
      activity, markedly increased in response to cold and salt treatments; however, no
      change in the protein level was observed, suggesting a posttranslational
      activation mechanism. The activation of the STY kinase is detected after 12 to 48
      h of cold and salt treatments, which indicates that the kinase may not
      participate in the initial response to abiotic stresses, but may play a possible
      role in the adaptive process to adverse conditions. The transcript levels and
      kinase activity were unaltered with abscisic acid treatment, suggesting an
      abscisic acid-independent cold and salt signaling pathway. Here, we report the
      first identification of a non-MAP kinase cascade dual-specificity kinase involved
      in abiotic stress and seed development.

PMID- 12226518
TI  - N-acylethanolamines are metabolized by lipoxygenase and amidohydrolase in
      competing pathways during cottonseed imbibition.
AB  - Saturated and unsaturated N-acylethanolamines (NAEs) occur in desiccated seeds
      primarily as 16C and 18C species with N-palmitoylethanolamine and N
      linoleoylethanolamine (NAE 18:2) being most abundant. Here, we examined the
      metabolic fate of NAEs in vitro and in vivo in imbibed cotton (Gossypium
      hirsutum) seeds. When synthetic [1-(14)C]N-palmitoylethanolamine was used as a
      substrate, free fatty acids (FFA) were produced by extracts of imbibed
      cottonseeds. When synthetic [1-(14)C]NAE 18:2 was used as a substrate, FFA and an
      additional lipid product(s) were formed. On the basis of polarity, we presumed
      that the unidentified lipid was a product of the lipoxygenase (LOX) pathway and
      that inclusion of the characteristic LOX inhibitors nordihydroguaiaretic acid and
      eicosatetraynoic acid reduced its formation in vitro and in vivo. The conversion
      of NAE 18:2 in imbibed cottonseed extracts to 12-oxo-13-hydroxy-N-(9Z)
      octadecanoylethanolamine was confirmed by gas chromatography-mass spectrometry,
      indicating the presence of 13-LOX and 13-allene oxide synthase, which metabolized
      NAE 18:2. Cell fractionation studies showed that the NAE amidohydrolase,
      responsible for FFA production, was associated mostly with microsomes, whereas
      LOX, responsible for NAE 18:2-oxylipin production, was distributed in cytosol
      enriched fractions and microsomes. The highest activity toward NAE by
      amidohydrolase was observed 4 to 8 h after imbibition and by LOX 8 h after
      imbibition. Our results collectively indicate that two pathways exist for NAE
      metabolism during seed imbibition: one to hydrolyze NAEs in a manner similar to
      the inactivation of endocannabinoid mediators in animal systems and the other to
      form novel NAE-derived oxylipins. The rapid depletion of NAEs by these pathways
      continues to point to a role for NAE metabolites in seed germination.

PMID- 12226519
TI  - Loss of nuclear gene expression during the phytochrome A-mediated far-red block
      of greening response.
AB  - We have examined the expression of the HEMA1 gene, which encodes the key
      chlorophyll synthesis enzyme glutamyl-tRNA reductase, during the phytochrome A
      mediated far-red light (FR) block of greening response in Arabidopsis. Our
      results demonstrate that the FR block of greening comprises two separate
      responses: a white light (WL) intensity-independent response that requires 3 d of
      FR and is associated with a loss of expression of the nuclear genes HEMA1 and
      Lhcb following the transfer to WL (transcriptionally coupled response) and a WL
      intensity-dependent response that is induced by 1 d of FR and is
      transcriptionally uncoupled. Both responses required phytochrome A. The
      transcriptionally uncoupled response correlated with a deregulation of
      tetrapyrrole synthesis and potential photooxidative damage and was inhibited by
      cytokinin. The transcriptionally coupled FR response was additive with the loss
      of expression following Norflurazon-induced photobleaching and was absent in the
      presence of sucrose or after lower fluence rate (1 micromol m(-2) s(-1)) FR
      treatments. Both pathways leading to the loss of nuclear gene expression were
      inhibited by overexpression of NADPH:protochlorophyllide oxidoreductase,
      indicating a role for plastid signaling in the FR-mediated pathway. The
      significance of identifying a distinct phytochrome A-mediated plastid signaling
      pathway is discussed.

PMID- 12226520
TI  - Short-term boron deprivation inhibits endocytosis of cell wall pectins in
      meristematic cells of maize and wheat root apices.
AB  - By using immunofluorescence microscopy, we observed rapidly altered distribution
      patterns of cell wall pectins in meristematic cells of maize (Zea mays) and wheat
      (Triticum aestivum) root apices. This response was shown for homogalacturonan
      pectins characterized by a low level (up to 40%) of methylesterification and for
      rhamnogalacturonan II pectins cross-linked by a borate diol diester. Under boron
      deprivation, abundance of these pectins rapidly increased in cell walls, whereas
      their internalization was inhibited, as evidenced by a reduced and even blocked
      accumulation of these cell wall pectins within brefeldin A-induced compartments.
      In contrast, root cells of species sensitive to the boron deprivation, like
      zucchini (Cucurbita pepo) and alfalfa (Medicago sativa), do not internalize cell
      wall pectins into brefeldin A compartments and do not show accumulation of
      pectins in their cell walls under boron deprivation. For maize and wheat root
      apices, we favor an apoplastic target for the primary action of boron
      deprivation, which signals deeper into the cell via endocytosis-mediated pectin
      signaling along putative cell wall-plasma membrane-cytoskeleton continuum.

PMID- 12226521
TI  - F-actin-dependent endocytosis of cell wall pectins in meristematic root cells.
      Insights from brefeldin A-induced compartments.
AB  - Brefeldin A (BFA) inhibits exocytosis but allows endocytosis, making it a
      valuable agent to identify molecules that recycle at cell peripheries. In plants,
      formation of large intracellular compartments in response to BFA treatment is a
      unique feature of some, but not all, cells. Here, we have analyzed assembly and
      distribution of BFA compartments in development- and tissue-specific contexts of
      growing maize (Zea mays) root apices. Surprisingly, these unique compartments
      formed only in meristematic cells of the root body. On the other hand, BFA
      compartments were absent from secretory cells of root cap periphery, metaxylem
      cells, and most elongating cells, all of which are active in exocytosis. We
      report that cell wall pectin epitopes counting rhamnogalacturonan II dimers cross
      linked by borate diol diester, partially esterified (up to 40%) homogalacturonan
      pectins, and (1-->4)-beta-D-galactan side chains of rhamnogalacturonan I were
      internalized into BFA compartments. In contrast, Golgi-derived secretory
      (esterified up to 80%) homogalacturonan pectins localized to the cytoplasm in
      control cells and did not accumulate within characteristic BFA compartments.
      Latrunculin B-mediated depolymerization of F-actin inhibited internalization and
      accumulation of cell wall pectins within intracellular BFA compartments.
      Importantly, cold treatment and protoplasting prevented internalization of wall
      pectins into root cells upon BFA treatment. These observations suggest that cell
      wall pectins of meristematic maize root cells undergo rapid endocytosis in an F
      actin-dependent manner.

PMID- 12226522
TI  - Arabinoxylan biosynthesis in wheat. Characterization of arabinosyltransferase
      activity in Golgi membranes.
AB  - Arabinoxylan arabinosyltransferase (AX-AraT) activity was investigated using
      microsomes and Golgi vesicles isolated from wheat (Triticum aestivum) seedlings.
      Incubation of microsomes with UDP-[(14)C]-beta-L-arabinopyranose resulted in
      incorporation of radioactivity into two different products, although most of the
      radioactivity was present in xylose (Xyl), indicating a high degree of UDP
      arabinose (Ara) epimerization. In isolated Golgi vesicles, the epimerization was
      negligible, and incubation with UDP-[(14)C]Ara resulted in formation of a product
      that could be solubilized with proteinase K. In contrast, when Golgi vesicles
      were incubated with UDP-[(14)C]Ara in the presence of unlabeled UDP-Xyl, the
      product obtained could be solubilized with xylanase, whereas proteinase K had no
      effect. Thus, the AX-AraT is dependent on the synthesis of unsubstituted xylan
      acting as acceptor. Further analysis of the radiolabeled product formed in the
      presence of unlabeled UDP-Xyl revealed that it had an apparent molecular mass of
      approximately 500 kD. Furthermore, the total incorporation of [(14)C]Ara was
      dependent on the time of incubation and the amount of Golgi protein used. AX-AraT
      activity had a pH optimum at 6, and required the presence of divalent cations,
      Mn(2+) being the most efficient. In the absence of UDP-Xyl, a single
      arabinosylated protein with an apparent molecular mass of 40 kD was radiolabeled.
      The [(14)C]Ara labeling became reversible by adding unlabeled UDP-Xyl to the
      reaction medium. The possible role of this protein in arabinoxylan biosynthesis
      is discussed.

PMID- 12226523
TI  - Patterns of expression and normalized levels of the five Arabidopsis
      phytochromes.
AB  - Using monoclonal antibodies specific for each apoprotein and full-length purified
      apoprotein standards, the levels of the five Arabidopsis phytochromes and their
      patterns of expression in seedlings and mature plants and under different light
      conditions have been characterized. Phytochrome levels are normalized to the DNA
      content of the various tissue extracts to approximate normalization to the number
      of cells in the tissue. One phytochrome, phytochrome A, is highly light labile.
      The other four phytochromes are much more light stable, although among these,
      phytochromes B and C are reduced 4- to 5-fold in red- or white-light-grown
      seedlings compared with dark-grown seedlings. The total amount of extractable
      phytochrome is 23-fold lower in light-grown than dark-grown tissues, and the
      percent ratios of the five phytochromes, A:B:C:D:E, are measured as
      85:10:2:1.5:1.5 in etiolated seedlings and 5:40:15:15:25 in seedlings grown in
      continuous white light. The four light-stable phytochromes are present at nearly
      unchanging levels throughout the course of development of mature rosette and
      reproductive-stage plants and are present in leaves, stems, roots, and flowers.
      Phytochrome protein expression patterns over the course of seed germination and
      under diurnal and circadian light cycles are also characterized. Little cycling
      in response to photoperiod is observed, and this very low amplitude cycling of
      some phytochrome proteins is out of phase with previously reported cycling of PHY
      mRNA levels. These studies indicate that, with the exception of phytochrome A,
      the family of phytochrome photoreceptors in Arabidopsis constitutes a quite
      stable and very broadly distributed array of sensory molecules.

PMID- 12226524
TI  - Characterization of a strong dominant phytochrome A mutation unique to
      phytochrome A signal propagation.
AB  - Here, we report the isolation and characterization of a strong dominant-negative
      phytochrome A (phyA) mutation (phyA-300D) in Arabidopsis. This mutation carries a
      single amino acid substitution at residue 631, from valine to methionine (V631M),
      in the core region within the C-terminal half of PHYA. This PHYA core region
      contains two protein-interactive motifs, PAS1 and PAS2. Val-631 is located within
      the PAS1 motif. The phyA-V631M mutant protein is photochemically active and
      accumulates to a level similar to wild type in dark-grown seedlings.
      Overexpression of PHYA-V631M in a wild-type background results in a dominant
      negative interference with endogenous wild-type phyA, whereas PHYA-V631M in a
      phyA null mutant background is inactive. To investigate the specificity of this
      mutation within the phytochrome family, the corresponding amino acid substitution
      (V664M) was created in the PHYTOCHROME B (PHYB) polypeptide. We found that the
      phyB-V664M mutant protein is physiologically active in phyB mutant and causes no
      interfering effect in a wild-type background. Together, our results reveal a
      unique feature in phyA signal propagation through the C-terminal core region.

PMID- 12226525
TI  - Characterization of an acyltransferase capable of synthesizing benzylbenzoate and
      other volatile esters in flowers and damaged leaves of Clarkia breweri.
AB  - A cDNA encoding a protein with 456 amino acids whose sequence shows considerable
      similarity to plant acyltransferases was identified among 750 Clarkia breweri
      flower expressed sequence tags. The cDNA was expressed in Escherichia coli, and
      the protein produced was shown to encode the enzyme benzoyl-coenzyme A
      (CoA):benzyl alcohol benzoyl transferase (BEBT). BEBT catalyzes the formation of
      benzylbenzoate, a minor constituent of the C. breweri floral aroma, but it also
      has activity with a number of other alcohols and acyl CoAs. The BEBT gene is
      expressed in different parts of the flowers with maximal RNA transcript levels in
      the stigma, and no expression was observed in the leaves under normal conditions.
      However, BEBT expression was induced in damaged leaves, reaching a maximum 6 h
      after damage occurred. We also show here that a closely related tobacco
      (Nicotiana tabacum) gene previously shown to be induced in leaves after being
      challenged by phytopathogenic bacteria also has BEBT activity, whereas the most
      similar protein to BEBT in the Arabidopsis proteome does not use benzoyl CoA as a
      substrate and instead can use acetyl CoA to catalyze the formation of cis-3-hexen
      1-yl acetate, a green-leaf volatile.

PMID- 12226526
TI  - Cloning and functional characterization of a beta-pinene synthase from Artemisia
      annua that shows a circadian pattern of expression.
AB  - Artemisia annua plants produce a broad range of volatile compounds, including
      monoterpenes, which contribute to the characteristic fragrance of this medicinal
      species. A cDNA clone, QH6, contained an open reading frame encoding a 582-amino
      acid protein that showed high sequence identity to plant monoterpene synthases.
      The prokaryotically expressed QH6 fusion protein converted geranyl diphosphate to
      (-)-beta-pinene and (-)-alpha-pinene in a 94:6 ratio. QH6 was predominantly
      expressed in juvenile leaves 2 weeks postsprouting. QH6 transcript levels were
      transiently reduced following mechanical wounding or fungal elicitor treatment,
      suggesting that this gene is not directly involved in defense reaction induced by
      either of these treatments. Under a photoperiod of 12 h/12 h (light/dark), the
      abundance of QH6 transcripts fluctuated in a diurnal pattern that ebbed around 3
      h before daybreak (9th h in the dark phase) and peaked after 9 h in light (9th h
      in the light phase). The contents of (-)-beta-pinene in juvenile leaves and in
      emitted volatiles also varied in a diurnal rhythm, correlating strongly with mRNA
      accumulation. When A. annua was entrained by constant light or constant dark
      conditions, QH6 transcript accumulation continued to fluctuate with circadian
      rhythms. Under constant light, advanced cycles of fluctuation of QH6 transcript
      levels were observed, and under constant dark, the cycle was delayed. However,
      the original diurnal pattern could be regained when the plants were returned to
      the normal light/dark (12 h/12 h) photoperiod. This is the first report that
      monoterpene biosynthesis is transcriptionally regulated in a circadian pattern.

PMID- 12226527
TI  - Nitric oxide negatively modulates wound signaling in tomato plants.
AB  - Synthesis of proteinase inhibitor I protein in response to wounding in leaves of
      excised tomato (Lycopersicon esculentum) plants was inhibited by NO donors sodium
      nitroprusside and S-nitroso-N-acetyl-penicillamine. The inhibition was reversed
      by supplying the plants with the NO scavenger 2-(4-carboxiphenyl)-4,4,5,5
      tetramethylimidazoline-1-oxyl-3-oxide. NO also blocked the hydrogen peroxide
      (H(2)O(2)) production and proteinase inhibitor synthesis that was induced by
      systemin, oligouronides, and jasmonic acid (JA). However, H(2)O(2) generated by
      glucose oxidase and glucose was not blocked by NO, nor was H(2)O(2)-induced
      proteinase inhibitor synthesis. Although the expression of proteinase inhibitor
      genes in response to JA was inhibited by NO, the expression of wound signaling
      associated genes was not. The inhibition of wound-inducible H(2)O(2) generation
      and proteinase inhibitor gene expression by NO was not due to an increase in
      salicylic acid, which is known to inhibit the octadecanoid pathway. Instead, NO
      appears to be interacting directly with the signaling pathway downstream from JA
      synthesis, upstream of H(2)O(2) synthesis. The results suggest that NO may have a
      role in down-regulating the expression of wound-inducible defense genes during
      pathogenesis.

PMID- 12226528
TI  - Resistance of cultivated tomato to cell content-feeding herbivores is regulated
      by the octadecanoid-signaling pathway.
AB  - The octadecanoid signaling pathway has been shown to play an important role in
      plant defense against various chewing insects and some pathogenic fungi. Here, we
      examined the interaction of a cell-content feeding arachnid herbivore, the two
      spotted spider mite (Tetranychus urticae Koch), with cultivated tomato
      (Lycopersicon esculentum) and an isogenic mutant line (defenseless-1 [def-1])
      that is deficient in the biosynthesis of the octadecanoid pathway-derived signal,
      jasmonic acid (JA). Spider mite feeding and fecundity on def-1 plants was
      significantly greater than on wild-type plants. Decreased resistance of def-1
      plants was correlated with reduced JA accumulation and expression of defensive
      proteinase inhibitor (PI) genes, which were induced in mite-damaged wild-type
      leaves. Treatment of def-1 plants with methyl-JA restored resistance to spider
      mite feeding and reduced the fecundity of female mites. Plants expressing a
      35S::prosystemin transgene that constitutively activates the octadecanoid pathway
      in a Def-1-dependent manner were highly resistant to attack by spider mites and
      western flower thrips (Frankliniella occidentalis), another cell-content feeder
      of economic importance. These findings indicate that activation of the
      octadecanoid signaling pathway promotes resistance of tomato to a broad spectrum
      of herbivores. The techniques of amplified fragment length polymorphism (AFLP)
      and bulk segregant analysis were used to map the Def-1 gene to a region on the
      long arm of chromosome 3 that is genetically separable from the map position of
      known JA biosynthetic genes. Tight linkage of Def-1 to a T-DNA insertion
      harboring the maize (Zea mays) Dissociation transposable element suggests a
      strategy for directed transposon tagging of the gene.

PMID- 12226531
TI  - Abeta deposition is essential to AD neuropathology.

PMID- 12226529
TI  - Regulation of transcript levels of the Arabidopsis cytochrome p450 genes involved
      in brassinosteroid biosynthesis.
AB  - Cytochrome P450 enzymes of the closely related CYP90 and CYP85 families catalyze
      essential oxidative reactions in the biosynthesis of brassinosteroid (BR)
      hormones. Arabidopsis CYP90B1/DWF4 and CYP90A1/CPD are responsible for respective
      C-22 and C-23 hydroxylation of the steroid side chain and CYP85A1 catalyzes C-6
      oxidation of 6-deoxo intermediates, whereas the functions of CYP90C1/ROT3,
      CYP90D1, and CYP85A2 are still unknown. Semiquantitative reverse transcriptase
      polymerase chain reaction analyses show that transcript levels of CYP85 and CYP90
      genes are down-regulated by brassinolide, the end product of the BR biosynthesis
      pathway. Feedback control of the CYP90C1, CYP90D1, and CYP85A2 genes by
      brassinolide suggests that the corresponding enzymes might also participate in BR
      synthesis. CYP85 and CYP90 mRNAs show strong and transient accumulation during
      the 1st week of seedling development, as well as characteristic organ-specific
      distribution. Transcripts of CYP90A1 and CYP85A2 are preferentially represented
      in shoots and CYP90C1, CYP90D1, and CYP85A1 mRNAs are more abundant in roots,
      whereas CYP90B1 is ubiquitously expressed. Remarkably, the spatial pattern of
      CYP90A1 expression is maintained in the BR-insensitive cbb2 mutant, indicating
      the independence of organ-specific and BR-dependent regulation. Quantitative gas
      chromatography-mass spectrometry analysis of endogenous BRs in shoots and roots
      of Arabidopsis, pea (Pisum sativum), and tomato (Lycopersicon esculentum) reveal
      similar partitioning patterns of BR intermediates in these species. Inverse
      correlation between CYP90A1/CPD transcript levels and the amounts of the CYP90A1
      substrate 6-deoxocathasterone in shoots and roots suggests that transcriptional
      regulation plays an important role in controlling BR biosynthesis.

PMID- 12226532
TI  - ApoE4: is it the absence of good or the presence of bad?

PMID- 12226533
TI  - Apolipoprotein E and Alzheimer's disease: the protective effects of ApoE2 and E3.

PMID- 12226534
TI  - The presence of apoE4, not the absence of apoE3, contributes to AD pathology.

PMID- 12226535
TI  - You can take the genome out of the organism, but can you take the organism out of
      the environment?

PMID- 12226536
TI  - Non-familial Alzheimer's disease is mainly due to genetic factors.
AB  - This team takes the position that what is commonly referred to as non-familial
      Alzheimer's disease (AD) is predominantly due to genetic factors. Population
      based studies suggest that genetic factors cause the majority of cases that begin
      after age 60. There are several lines of evidence supporting this position: Data
      from the Nun Study suggest that the risk for AD is largely established by early
      adulthood, implying that later adult exposures likely play only a small role in
      causation. Family studies show that first-degree blood relatives of persons with
      non-familial AD have a substantially increased risk of AD relative to controls.
      Twin studies suggest that the heritability of AD exceeds 60%. Environmental
      factors, such as socioeconomic status, education, and head injury, are strong
      risk factors for AD only in individuals with a genetic predisposition. The APOE
      genotype is a powerful risk factor for AD and accounts for as much as 50%. There
      are numerous other candidate genes with strong associations with AD that
      presumably explain the remaining population risk. This paper further reviews the
      mechanisms associated with AD causation for APOE and other candidate genes and
      implications for the development of prevention strategies.

PMID- 12226537
TI  - The significance of environmental factors in the etiology of Alzheimer's disease.
AB  - The proposition that environmental agents, such as diet, aluminum, and viruses,
      are as important as genetic factors in the etiology of Alzheimer's disease (AD)
      was advanced by the authors at the Challenging Views of Alzheimer's Disease
      meeting held in Cincinnati on July 28 and 29, 2001. Diet, dietary fat, and to a
      lesser extent, total energy (caloric intake), were found to be significant risk
      factors for the development of AD in a dozen countries, while fish consumption
      was found to be a significant risk reduction factor. An acid-forming diet, such
      as one high in dietary fat or total energy, can lead to increased serum and brain
      concentrations of aluminum and transition metal ions, which are implicated in
      oxidative stress potentially leading to the neurological damage characteristic of
      AD. Many of the risk factors for AD, such as cholesterol and fat, and risk
      reduction factors, such as whole grain cereals and vegetables, are shared with
      ischemic heart disease. Aluminum may cause neurological damage and a number of
      studies have linked aluminum to an increased risk for developing AD. The evidence
      for viral agents playing a role in AD is the strong association between the
      presence of HSV1 in brain and carriage of an apoE-epsilon4 allele in the case of
      AD patients but not of controls; statistical analysis shows the association is
      causal. Diet, aluminum, and viral infections may increase the prevalence of AD by
      eliciting inflammation, which may cause the neurological damage that results in
      AD.

PMID- 12226538
TI  - Amyloid beta-peptide and amyloid pathology are central to the oxidative stress
      and inflammatory cascades under which Alzheimer's disease brain exists.
AB  - Alzheimer's disease (AD) brain is characterized by excess deposition of amyloid
      beta-peptide (Abeta), particularly the 42-amino acid peptide [Abeta(1-42)] and by
      extensive oxidative stress. Several sources of the oxidative stress and
      inflammatory cascades are likely, including that induced by advanced glycation
      end products, microglial activation, and by Abeta(1-42) and its sequelae. This
      review briefly examines each of these sources of oxidative stress and
      inflammation in AD brain and discusses their potential roles in the clinical
      progression of AD dementia.

PMID- 12226539
TI  - Amyloid-beta: redox-metal chelator and antioxidant.

PMID- 12226540
TI  - The cerebromicrovasculature: a key player in the pathogenesis of Alzheimer's
      disease.
AB  - Neuronal cell death is the primary underlying pathogenic lesion in Alzheimer's
      disease (AD). Despite intense research efforts, the mechanisms that contribute to
      neuronal cell death have not been clarified. In this debate we address the
      question, Is AD a vascular or metabolic disorder? Here we defend the hypothesis
      that the cerebromicrovasculature is a key player in the pathogenesis of AD.
      Evidence is presented that vascular amyloid beta (Abeta) is more closely
      associated with tau pathology than the distribution of diffuse or neuritic plaque
      Abeta. Furthermore, brain endothelial cells are identified as important
      regulators of the neuronal microenvironment, including Abeta levels. Finally,
      evidence is presented that brain endothelial cells undergo cellular and
      biochemical changes in AD and that the release of neurotoxic factors from these
      dysfunctional cells contributes to the neuronal cell loss characteristic of AD.

PMID- 12226541
TI  - The role of the metabolic lesion in Alzheimer's disease.
AB  - This paper discusses the hypothesis that the cerebrometabolic deficiency in
      Alzheimer's disease(AD) is the proximate cause of the clinical disability.
      Several sets of observations support this hypothesis. (1) Impaired brain
      metabolism essentially always occurs in clinically significant AD, and the degree
      of clinical disability is proportional to the degree of metabolic impairment. The
      earliest, mildest changes in brain metabolism occur even before the onset of
      measurable cognitive impairment or atrophy. This observation disproves the now
      outdated assumption that the decreased metabolism is simply a consequence of
      decreased mental function or of atrophy. One of the important mechanisms reducing
      brain metabolism in AD appears to be damage to key mitochondrial components.
      Another appears to relate to inappropriate responses to insulin, i.e. to diabetes
      of the brain. (2) Inducing impairments of brain metabolism causes changes in
      mentation that mimic the clinical disabilities in AD, in both humans and
      experimental animals. (3) Preliminary results from several units suggest that
      treatment directed at the impairment of brain metabolism can improve
      neuropsychological functions in AD patients. The hypothesis presented here in no
      way negates the importance of other mechanisms in AD, such as amyloid
      accumulation, vascular compromise, and free radical action. However, those other
      abnormalities including amyloidosis can occur in people whose mentation is still
      clinically unimpaired. In contrast, once significant decrease in the rate of
      brain metabolism occurs, mentation becomes defective.

PMID- 12226543
TI  - Cyclin towards, or away from, dementia?

PMID- 12226542
TI  - Neurofibrillary pathology leads to synaptic loss and not the other way around in
      Alzheimer disease.

PMID- 12226544
TI  - Re-expression of cell cycle proteins induces neuronal cell death during
      Alzheimer's disease.

PMID- 12226545
TI  - Cell cycle proteins in Alzheimer's disease: plenty of wheels but no cycle.

PMID- 12226546
TI  - What evidence would prove the amyloid hypothesis? Towards rational drug
      treatments for Alzheimer's disease.

PMID- 12226547
TI  - Association between preheparin serum lipoprotein lipase mass and acute myocardial
      infarction in Japanese men.
AB  - A sensitive immunoassay system using a specific monoclonal antibody against
      lipoprotein lipase (LPL) recently demonstrated the presence of an LPL mass in
      preheparin serum. We reported that a preheparin serum LPL mass (pre-LPL mass)
      reflected the level of functioning LPL activity in the whole body and could be
      deeply involved in the progression of coronary atherosclerosis of stable organic
      angina pectoris. We examined the relation between the pre-LPL mass and acute
      myocardial infarction (AMI). We studied 44 males with AMI (AMI group) and 16
      males with a normal coronary artery (NCA group), and measured the pre-LPL mass by
      enzyme-linked immunosorbent assay. Coronary risk factors including the pre-LPL
      mass were compared between the two groups and multiple regression analysis was
      performed for AMI. There were no significant differences in the lipid data, but
      the pre-LPL mass level was significantly low in the AMI group (52 +/- 16 vs 41 +/
      14 ng/ml, p = 0.01), and a low pre-LPL mass concentration was observed in the
      small sized LDL group and/or the Midband positive group. Multiple regression
      analysis revealed that a low pre-LPL mass and hypertriglyceridemia were
      independent risk factors for AMI (t value = 2.1, 2.4). The result indicates that
      a low pre-LPL mass may be an important risk factor for AMI and stable organic
      angina pectoris.

PMID- 12226548
TI  - Changes in aspects such as the collagenous fiber density and foam cell size of
      atherosclerotic lesions composed of foam cells, smooth muscle cells and fibrous
      components in rabbits caused by all-cis-5, 8, 11, 14, 17-icosapentaenoic acid.
AB  - Atherosclerotic plaques composed of foamed macrophages, smooth muscle cells and
      fibrous components in the twice-injured carotid artery from 1% cholesterol diet
      (HCD)-fed rabbits were prepared and the effects of all-cis-5, 8, 11, 14, 17
      icosapentaenoic acid (EPA) on the histopathological properties of atherosclerotic
      lesions were examined. During the test period, there was no significant
      difference between the control and the EPA-treated groups in serum lipid levels.
      In the control group, atherosclerotic lesions were composed of foamed
      macrophages, smooth muscle cells and fibrous components. Some of the lesions had
      a large core of foamed macrophages covered with a thin cap of smooth muscle cells
      and fibrous components, and were morphologically similar to human vulnerable
      plaques. The classification of plaques, composing atherosclerotic lesions based
      on collagenous fiber density and foam cell size indicated that over 70% of
      plaques in the control group were poor in collagenous fiber, while about 20% of
      plaques contained only large foam cells. In contrast to the control group, over
      70% of plaques in the EPA-treated group were rich in collagenous fiber and only
      3% consisted of large foam cells. These results suggest that EPA changes certain
      aspects of pre-existing atherosclerotic lesions.

PMID- 12226549
TI  - The effect of statins on mRNA levels of genes related to inflammation,
      coagulation, and vascular constriction in HUVEC. Human umbilical vein endothelial
      cells.
AB  - Large-scale clinical trials have demonstrated significant reductions in
      cardiovascular events following statin therapy. The observed benefit of statin
      therapy, however, may be greater in these trials than is to be expected from
      lowering lipid levels alone. In order to clarify the mechanism by which statins
      prevent cardiovascular events in vascular wall cells, we investigated the changes
      in gene expression profiles after incubation with atorvastatin or pitavastatin in
      cultured human umbilical vein endothelial cells using DNA microarrays. Statins
      affected the expression levels of genes involved in inflammation, coagulation,
      and vascular constriction. The mRNA levels for interleukin-8 (IL-8) and monocyte
      chemoattractant protein-1 (MCP-1) decreased after statin treatment. Statins
      reduced mRNA levels of plasminogen activator inhibitor-1 (PAI-1) and increased
      the mRNA levels of thrombomodulin. Statins reduced the mRNA levels of endothelin
      1 and increased the mRNA levels of nitric oxide synthase-3 (eNOS). These results
      show that, statins are clinically effective because of their ability to change
      the gene expression profile of endothelial cells thereby preventing vascular
      events.

PMID- 12226550
TI  - Expressional changes of the vascular antioxidant system in atherosclerotic
      coronary arteries.
AB  - Oxidative stress induced by reactive oxygen species (ROS) plays an important role
      in atherogenesis, and the redox state is determined by the balance between
      antioxidants and the ROS generating system. To defend against enhanced ROS,
      mammalian cells have a complex network of antioxidant enzymes such as superoxide
      dismutase (SOD), glutathione peroxidase (GPx) and catalase. To clarify the role
      of the vascular antioxidant system, we investigated by immunohistochemistry the
      expressional changes of antioxidative enzymes in coronary arteries obtained from
      autopsied cases. In nonatherosclerotic coronary arteries, Cu/Zn SOD and Mn SOD
      were expressed in medial smooth muscle cells (SMC), whereas cytosolic GPx (GPx-1)
      was expressed mainly in endothelium and weakly in medial SMC. Catalase was
      expressed in medial SMC and endothelium. Progression of atherosclerosis did not
      result in an additional increase in the expression of antioxidative enzymes in
      SMC in the media or endothelium. However, migrating SMC and macrophages in
      atheromatous plaques expressed these four antioxidative enzymes intensively.
      Double staining with cell markers confirmed the cell-specific expression of the
      antioxidative enzymes. Thus, the expressional pattern showed regional
      heterogeneity. In response to oxidative stress, the vascular antioxidant system
      was upregulated in atherosclerotic lesions. The imbalance between vascular
      antioxidant and oxidant systems might play an important role in coronary
      atherogenesis.

PMID- 12226551
TI  - Risk factors for coronary heart disease in the Japanese--comparison of the
      background of patients with acute coronary syndrome in the ASPAC study with data
      obtained from the general population. Asia-Pacific Collaboration on CHD Risk
      Factor Intervention study.
AB  - The relative importance of metabolic risk factors for coronary heart disease
      (CHD) in the Japanese is assessed by comparing their prevalence in patients with
      acute coronary syndrome (ACS) enrolled in the Asia-Pacific Collaboration on CHD
      Risk Factor Intervention (ASPAC) study to that obtained by a serum lipid survey
      carried out in 1990 and also by comparing them to the ASPAC data from other
      countries and regions in this area. Hypertension was the most prevalent risk
      factor among Japanese patients with ACS as in the other countries and regions.
      The prevalence of obesity with a body mass index (BMI) of 30 or more was several
      times higher than that in the general population, although the rate was still
      much lower than in New Zealand and Singapore. In addition to
      hypercholesterolemia, hypertriglyceridemia and diabetes mellitus were frequently
      found in Japanese patients with ACS. When the prevalence of metabolic risk
      factors was compared between people with and without hypertension in the general
      population, the most remarkable difference was seen in BMI, followed by
      triglyceride and total cholesterol. These results indicate that
      hypertriglyceridemia and diabetes mellitus may be more important CHD risk factors
      in the Japanese population than LDL-cholesterol.

PMID- 12226552
TI  - NAD (P) H oxidase p22 phox C242T polymorphism affects LDL particle size and
      insulin resistance in Japanese subjects.
AB  - Elevated cardiovascular risk is associated with an increased number of small,
      dense low-density lipoprotein (LDL) particles, which exhibit increased
      susceptibility to lipid oxidation, however, the mechanism determining LDL
      particle size has never been fully elucidated. We have examined the association
      between the C242T polymorphism of the p22 phox gene, which is a small subunit of
      vascular NAD(P)H oxidase, and both LDL particle size and clinical characteristics
      in 260 healthy subjects. Peak LDL particle diameter (LDL-PPD) was measured by
      continuous disk polyacrylamide gel electrophoresis. Twenty-one of the 217
      subjects with the CC genotype showed pattern B (median LDL-PPD under 25.5 nm),
      whereas, none of the 43 subjects with TC + TT genotypes showed pattern B. The
      pattern B fraction was significantly larger in the CC group than in the TC + TT
      group (p = 0.030). The subjects with the CC genotype also showed a significantly
      higher fasting glucose level, plasma insulin level, and insulin resistance index
      of homeostasis model assessment (HOMA-R) than those with the TC + TT genotype.
      Our data demonstrate that variation in the small NAD(P)H oxidase subunit p22 phox
      gene substantially influences LDL particle size and may also reflect differences
      in the insulin sensitivity of non-diabetic subjects.

PMID- 12226553
TI  - Waist-to-height ratio is the best predictor of cardiovascular disease risk
      factors in Japanese schoolchildren.
AB  - In adults, visceral fat accumulation is an important indicator for cardiovascular
      disease risk. This relationship is not fully understood in children. To determine
      the best predictor of cardiovascular disease risk factors among anthropometric
      indices such as body mass index (BMI), percent body fat (%Fat), waist-to-hip
      ratio (WHR), waist circumference, and waist-to-height ratio (W/Ht ratio) in
      Japanese schoolchildren. This study included 880 children (447 boys and 433
      girls), 9-13y of age. Dependent variables were total cholesterol (TC),
      triglycerides (TG), high-density lipoprotein cholesterol (HDLC), low-density
      lipoprotein cholesterol (LDLC), atherogenic index (AI), life style related
      disease prevention score, and systolic (SBP) and diastolic (DBP) blood pressure.
      The strongest correlation was found between W/Ht ratio and the score by Pearson's
      correlation analysis. Multiple regression analysis showed that significant
      independent correlates for the score included W/Ht ratio and %Fat. Among the
      anthropometric indices, W/Ht ratio was the most significant predictor for TC, TG,
      LDLC, AI, and the score. W/Ht ratio is the best predictor of cardiovascular risk
      factors in Japanese schoolchildren. We propose using W/Ht ratio for detecting
      cardiovascular disease risk in children.

PMID- 12226554
TI  - Serum paraoxonase (PON1) concentration in patients undergoing hemodialysis.
AB  - Cardiac death from atherosclerosis is common in patients undergoing hemodialysis.
      Although the enzymic activity of human serum paraoxonase (PON1) has been reported
      to be decreased in such patients, serum PON1 concentrations have not been
      measured. We investigated serum PON1 concentrations in 81 patients undergoing
      hemodialysis and 103 age-matched healthy subjects using an enzyme immunoassay.
      The PON1 concentration was significantly lower in the patient group than the
      control group (mean +/- SD: 6.78 +/- 3.56 vs 18.01 +/- 4.55 U/ml, respectively. p
      < 0.0001). There were no significant relationships between serum PON1
      concentrations and the PON1 genetic polymorphisms, 55Leu/Met (L/M) and 192Gln/Arg
      (Q/R). The concentration adjusted for HDL-cholesterol or apolipoprotein A-I was
      also lower in the patient group. However, the specific activities (enzyme
      activity divided by the PON1 concentration) of paraoxonase and arylesterase were
      increased in the patient group compared with the control group. In the male
      patients, but not the female patients, PON1 concentrations were significantly
      lower in subjects with than without coronary heart disease (CHD) (mean +/- SD:
      4.48 +/- 2.77 vs 7.34 +/- 3.22 U/ml, respectively. p < 0.01). In conclusion, the
      serum PON1 concentration in hemodialyzed patients was significantly decreased,
      resulting in an attenuation of PON1 enzymic activity. This decrease may be in
      part involved in the development of cardiovascular disease.

PMID- 12226555
TI  - Oxidized LDL antibodies (OLAB) in patients with beta-thalassemia major.
AB  - Thalassemic (TM) patients are subjected to peroxidative tissue injury because of
      continuous blood transfusions. It has been documented that circulating LDL from
      TM patients show marked oxidative modification, that could represent an event
      leading to atherogenesis. We investigated in 75 beta-TM patients the levels of
      oxidized LDL antibody (OLAB) to asses their correlation with total cholesterol,
      LDL and HDL cholesterol, triglycerides Apo A-1 and Apo B. OLAB/mg chol-LDL is
      greater in TM patients than healthy controls (p<0.001). No correlation was found
      between OLAB and age, sex of patients, mean blood consumption, mean serum
      ferritin, mean transaminases, PT, PTT, and fibrinogen. A significant positive
      correlation was found between OLAB and triglycerides in TM patients (p<0.001).
      Also a significant correlation was found between OLAB/mg chol-LDL and level of
      triglycerides in TM patients, but not with total cholesterol, LDL and HDL chols,
      Apo A-1 and Apo B. On the contrary in the healthy controls this correlation
      between OLAB and OLAB/mg chol-LDL versus triglycerides was negative and not
      significant. High levels of OLAB/mg chol-LDL in patients with beta-thalassemia,
      in absence of evident signs of atherosclerosis, suggest some regulatory
      mechanisms on the lipid peroxidation which modulate the deposition of ox-LDL in
      the macrophages and support the hypothesis that both serum iron and triglycerides
      are involved in the pathogenesis of LDL oxidation.

PMID- 12226556
TI  - A rapid PCR method of genotyping LDL receptor mutations in WHHL rabbits.
AB  - WHHL rabbits are a valuable model for the study of human familial
      hypercholesterolemia and atherosclerosis. To use this animal model, it is often
      necessary to confirm LDL receptor status in WHHL rabbits. Here, we described a
      simple and rapid PCR method to detect LDL mutations in WHHL rabbits.

PMID- 12226557
TI  - Effects of Lentinus edodes mycelia on dietary-induced atherosclerotic involvement
      in rabbit aorta.
AB  - Lentinus edodes mycelia lowers cholesterol levels and acts as an immunomodulator
      and tumor-inhibitor in animal models. Lentinus edodes mycelia contains
      eritadenine (C(9)H(11)O(4)N(5)) and glucans among other biological compounds.
      However, whether or not Lentinus edodes mycelia is anti-atherogenic remains
      unknown. We examined the effect of Lentinus edodes mycelia (L.E.M) on
      atherosclerosis in a rabbit model. Thirty-two Japanese white male rabbits were
      fed with 1.0% cholesterol for 8 weeks, then divided into groups and given 1) 1.0%
      cholesterol for over 8 weeks (control), 2) 1.0% cholesterol and 1.0% L.E.M for
      over 8 weeks, 3) 1.0% cholesterol and 2.0% L.E.M for over 8 weeks, and 4) 1.0%
      cholesterol and 4.0% L.E.M for over 8 weeks (n=8 each group). Total cholesterol
      (TC) was measured periodically throughout the experiment. After the experimental
      periods, the aortas were removed and atherosclerotic lesions were examined
      histologically, immunohistochemically and morphometrically to determine surface
      involvement (SI) and an atherosclerotic index (AI). Body weight and TC did not
      significantly differ among the four groups. Decreases in SI were significant in
      the 1% L.E.M (26.2+/-10.8%) and 2% L.E.M (29.3+/-15.7%) groups compared with the
      control (48.7+/-15.3%; p < 0.05). The AI was significantly decreased in the 1%
      L.E.M (6.62+/-4.31) and 2% L.E.M (7.49+/-3.49) groups compared with the control
      (16.96+/-9.21; p < 0.05). Foam cells aggregated in thickened intima of dietary
      induced atherosclerotic lesions in the rabbit aorta. In contrast, the numbers of
      foam cells in the intima decreased in the experimental group. No-cholesterol
      lowering action or dose-dependant effects of L.E.M were determined in this study,
      but atherosclerotic development was significantly inhibited, indicating that
      L.E.M had anti-atherogenic properties. L.E.M may inhibit atherosclerotic
      development in rabbit aorta and be beneficial as a nutritional supplement.

PMID- 12226558
TI  - Influence of polyunsaturated fatty acid on gene expression in HepG2 cells.

PMID- 12226559
TI  - Spike-based synaptic plasticity and the emergence of direction selective simple
      cells: simulation results.
AB  - Direction selectivity (DS) of simple cells in the primary visual cortex was
      recently suggested to arise from short-term synaptic depression in
      thalamocortical afferents (Chance F, Nelson S, Abbott L (1998), J. Neuroscience
      18(12): 4785-4799). In the model, two groups of afferents with spatially
      displaced receptive fields project through either depressing and non-depressing
      synapses onto the V1 cell. The degree of synaptic depression determines the
      temporal phase advance of the response to drifting gratings. We show that the
      spatial displacement and the appropriate degree of synaptic depression required
      for DS can develop within an unbiased input scenario by means of temporally
      asymmetric spike-timing dependent plasticity (STDP) which modifies both the
      synaptic strength and the degree of synaptic depression. Moving stimuli of random
      velocities and directions break any initial receptive field symmetry and produce
      DS. Frequency tuning curves and subthreshold membrane potentials akin to those
      measured for non-directional simple cells are thereby changed into those measured
      for directional cells. If STDP is such that down-regulation dominates up
      regulation the overall synaptic strength adapts in a self-organizing way such
      that eventually the postsynaptic response for the non-preferred direction becomes
      subthreshold. To prevent unlearning of the acquired DS by randomly changing
      stimulus directions an additional learning threshold is necessary. To further
      protect the development of the simple cell properties against noise in the
      stimulus, asynchronous and irregular synaptic inputs are required.

PMID- 12226560
TI  - The mystery of structure and function of sensory processing areas of the
      neocortex: a resolution.
AB  - Many different neural models have been proposed to account for major
      characteristics of the memory phenomenon family in primates. However, in spite of
      the large body of neurophysiological, anatomical and behavioral data, there is no
      direct evidence for supporting one model while falsifying the others. And yet, we
      can discriminate models based on their complexity and/or their predictive power.
      In this paper we present a computational framework with our basic assumption that
      neural information processing is performed by generative networks. A complex
      architecture is 'derived' by using information-theoretic principles. We find that
      our approach seems to uncover possible relations among the functional memory
      units (declarative and implicit memory) and the process of information encoding
      in primates. The architecture can also be related to the entorhinal-hippocampal
      loop. An effort is made to form a prototype of this computational architecture
      and to map it onto the functional units of the neocortex. This mapping leads us
      to claim that one may gain a better understanding by considering that anatomical
      and functional layers of the cortex differ. Philosophical consequences regarding
      the homunculus fallacy are also considered.

PMID- 12226561
TI  - Assessing the encoding of stimulus attributes with rapid sequences of stimulus
      events.
AB  - In a preceding paper (M. Eger and R. Eckhorn, J. Comput. Neurosci., 2002) we have
      published a three step method for the quantification of transinformation in multi
      input and -output neuronal systems. Here we present an extension that applies to
      rapid series of transient stimuli and thus, fills the gap between the discrete
      and continuous stimulation paradigm. While the three step method potentially
      captures all stimulus aspects, the present approach quantifies the
      discriminability of selected attributes of discrete stimuli and thus, assesses
      their encoding. Based on simulated and recorded data we investigate the
      performance of the implemented algorithm. Our approach is illustrated by analyses
      of neuronal population activity from the visual cortex of the cat, evoked by
      electrical stimuli of the retina.

PMID- 12226563
TI  - Modality-specific spike identification in simultaneous
      magnetoencephalography/electroencephalography: a methodological approach.
AB  - Epileptiform spikes may have a different morphology and signal-to-noise ratio in
      simultaneously recorded EEGs and magnetoencephalograms (MEGs) that may lead to
      differences in the identification of spikes if both the modalities are presented
      separately. Moreover, there are no criteria for MEG spikes. It is unknown to
      which extent the visual assessment of MEG data yields consistent and meaningful
      results. Nineteen patients were selected with mesial temporal lobe epilepsy who
      underwent whole-head simultaneous MEG/EEG. These data were split into MEG and EEG
      files and were assessed independently by three observers for the occurrence of
      spikes. Interobserver kappa values were calculated. A mean kappa value greater
      than 0.5 was taken as a criterion for the presence of unequivocal spikes. Index
      cases from the resulting four subgroups were studied further. One patient had
      unequivocal spikes in both modalities, one in EEG only, one in MEG only, and one
      did not show any unequivocal spike. Spikes on which at least two observers agreed
      were then subjected to a template match algorithm to test for equal morphology
      and distribution. Equal spikes were averaged and electrical and magnetic field
      maps were plotted. Unequivocal spikes were found in both MEG and EEG in one
      patient, in MEG only in two patients, in EEG only in two patients, and no spikes
      in either modality were seen in 14 patients. In the four index patients, MEG
      showed 50 to 80% more spikes than EEG. After averaging identical consensus
      spikes, MEG spikes revealed a concomitant spike in the EEG, but the reverse was
      not always true. Even in the patient with MEG and EEG spikes that met all
      selection criteria, simultaneous field maps showed unexpected inconsistencies. In
      most patients with mesial temporal lobe epilepsy, there are no unequivocal spikes
      during MEG/EEG. In some cases, however, experienced electroencephalographers can
      identify MEG spikes reliably. Because of a better signal-to-noise ratio, more
      spikes could be identified in MEG than in EEG. Simultaneous MEG/EEG recordings do
      not simply ensure the best of both, but one modality may improve the
      identification of spikes in the other. In addition, different aspects of a
      complex source can be revealed. Our three-step approach to combined data ensures
      a reproducible selection of spikes for source modeling.

PMID- 12226562
TI  - Modulatory effects of parallel fiber and molecular layer interneuron synaptic
      activity on purkinje cell responses to ascending segment input: a modeling study.
AB  - Based on anatomical, physiological, and model-based studies, it has been proposed
      that synapses associated with the ascending segment of granule cell axons provide
      the principle excitatory drive on Purkinje cells which is then modulated by the
      more numerous parallel fiber synapses. In this study we have evaluated this idea
      using a detailed compartmental model of a cerebellar Purkinje cell by providing
      identical ascending segment synaptic inputs during different levels of random
      parallel fiber and molecular interneuron input. Results suggest that background
      inputs from parallel fibers and molecular layer interneurons can have a
      substantial effect on the response of Purkinje cells to ascending segment inputs.
      Interestingly, these effects are not reflected in the average firing rate of the
      Purkinje cell and are thus entirely dendritic in effect. These results are
      considered in the context of the known segregated spatial distribution of the
      parallel fibers and ascending segment synapses and a new hypothesis concerning
      the functional organization of cerebellar cortical circuitry.

PMID- 12226564
TI  - Continuous potential display of ictal electrocorticography.
AB  - The objective of this study was to determine whether the animation of electrical
      activity recorded on ictal electrocorticograms (ECoGs) can demonstrate the
      propagation of seizure discharges from the epileptogenic zone (EZ) to the
      surrounding cortical area. A computer program, continuous potential display
      (CPD), was designed to animate the color-coded potential changes in 5-msec
      intervals at each recorded site. This program was used to analyze 35 ictal ECoGs
      recorded by subdural grid electrodes from 11 subjects who underwent epilepsy
      surgery for intractable partial seizures. Continuous potential display
      demonstrated recurrent cycles of seizure propagation from the EZ to the
      surrounding cortical area even when seizure discharges appeared widespread on
      ECoG. Hence, the EZ could be mapped at any time during the seizure course. The EZ
      mapped by analyzing a small fraction of ECoG during widespread seizure discharges
      using CPD only overlapped 69 +/- 24% (mean +/- standard deviation) of the
      surgical area. The EZ mapped by CPD had 34 +/- 22% false positives and 35 +/- 27%
      false negatives. Animation of potential changes recorded by ictal ECoG can assist
      in studying the temporal and spatial patterns of seizure propagation and in
      mapping the EZ for surgical resection.

PMID- 12226565
TI  - Daytime outpatient versus inpatient video-EEG monitoring for presurgical
      evaluation in temporal lobe epilepsy.
AB  - Video-EEG monitoring documentation of seizure localization is one of the most
      important aspects of a presurgical investigation in refractory temporal lobe
      epilepsy (TLE) patients. The objective of this study was to evaluate the efficacy
      of inpatient versus daytime outpatient telemetry. The authors evaluated
      prospectively 73 patients with medically intractable TLE. Ninety-one telemetry
      sessions were performed: 35 as inpatients and 56 as outpatients. Outpatient
      monitoring was performed in the EEG laboratory. They used 18-channel digital EEG.
      Medications were not changed in the outpatient group. For analysis of the data,
      time was counted in periods (12 hours = 1 period). Statistical analyses were
      performed using Student's t-test and the chi2 test. There were no differences
      between the two groups (outpatient versus inpatient) with respect to age and mean
      seizure frequency before monitoring, mean time to record the first seizure (1.1
      versus 1.4 periods), mean number of seizures per period (0.6 for both groups),
      lateralization by interictal spiking (46% versus 57%), and lateralization by
      ictal EEG (59% versus 77%). Daytime outpatient video-EEG monitoring for
      presurgical evaluation is efficient and comparable with inpatient monitoring.
      Therefore, the improved cost benefit of outpatient monitoring may increase the
      access to surgery for individuals with intractable TLE.

PMID- 12226566
TI  - Modification of the average reference montage: dynamic average reference.
AB  - The common average reference (CAR) is influenced strongly by high-amplitude
      artifacts at the recording electrodes. The authors suggest an algorithm for
      average reference modification that allows application of the average reference
      montage in the presence of high-amplitude artifacts at one or several EEG data
      channels. This dynamic average reference (DAR) method is based on analysis of
      kurtosis (DARkurt) or kurtosis and standard deviation (DARSD) of amplitude
      distribution at a single time point and elimination of outliers before
      calculating the average reference. This procedure can be performed on-line. The
      DAR improves visual EEG representation considerably in the presence of high
      amplitude artifacts. The DAR also influences artifact-free EEG, increasing
      slightly the amplitude of high-amplitude waveforms. The modeling of the dipole
      source in the spherical conductor has shown that the DAR compared with the CAR
      can both decrease and increase the average reference bias depending on position
      and orientation of the source. In practice, the influence of the DAR with tested
      parameters on the artifact-free EEG was low and never exceeded 12% of the
      amplitude of the CAR-referenced signal. The DAR method can be useful for routine
      analysis of EEG contaminated by high-amplitude artifacts and for long-term EEG
      monitoring.

PMID- 12226567
TI  - Dynamic changes in area 1 somatosensory cortex during transient sensory
      deprivation: a preliminary study.
AB  - To investigate the neural plasticity in the somatosensory cortex, changes in
      somatosensory evoked potentials (SSEPs) during finger ischemia were evaluated and
      compared with those affected by touch or movement interference. Somatosensory
      evoked potentials were recorded in the vicinity of the central sulcus in four
      patients with intractable epilepsy. During electrical stimulation to a selected
      finger, ischemic anesthesia was induced in another finger. Effects of tactile or
      movement interference were examined during electrical stimulation to the selected
      finger by applying tactile stimulation to or inducing voluntary movement of the
      other finger. Dynamic SSEPs were recorded during varying levels of sensory
      deprivation and different types of interference, and the dynamic nature of the
      SSEP changes within an individual was studied in detail. Somatosensory evoked
      potential changes appeared during finger ischemia and tended to persist during
      the postischemic stage, which is indicative of sensory plasticity and the
      maintenance of new conditioning. Amplitudes of the early and late cortical
      components increased when complete finger anesthesia was induced-a sign of the
      unmasking phenomenon. Amplitudes of early cortical SSEPs decreased when ischemic
      anesthesia was incomplete, similar to the findings when tactile or movement
      interference was applied. Surrounding inhibition, therefore, may become dominant
      before the unmasking phenomenon appears in early cortical SSEPs.

PMID- 12226568
TI  - Impaired sensorimotor integration in cervical dystonia: a study using
      transcranial magnetic stimulation and muscle vibration.
AB  - The authors studied the effects of sensorimotor integration (corticocortical
      inhibition and facilitation during muscle vibration [MV]) in dystonic patients.
      Eleven patients with cervical dystonia and 11 age-matched healthy control
      subjects were enrolled in the study. They were examined using transcranial
      magnetic stimulation (TMS) and tonic proprioceptive input (MV). Paired-pulse
      transcranial magnetic stimulation was done at interstimulus intervals of 3 msec
      (intracortical inhibition) and 13 msec, the intensity of the conditioning
      stimulus was 70% of the motor threshold, and the test stimulus was 120%. Motor
      evoked potentials were recorded from the vibrated extensor carpi radialis muscle
      and its antagonist, the flexor carpi radialis. Duration of MV trains (80 Hz;
      amplitude, 0.5 mm) was 4 seconds. The authors found differences between patients
      and healthy control subjects during MV only. Intracortical inhibition was
      pronounced significantly only in control subjects, whereas intracortical
      facilitation was significant in patients only (P < 0.05). Furthermore, the
      significant reduction of motor evoked potentials at 13-msec interstimulus
      intervals, which can be found in healthy subjects frequently, was observed in one
      dystonia patient only. The results of the current study suggest that sensorimotor
      integration is impaired in cervical dystonia, probably by an altered control of
      proprioceptive (vibratory) input.

PMID- 12226569
TI  - Effect of exercise on motor evoked potentials elicited by transcranial magnetic
      stimulation in psychiatric patients.
AB  - SUMMARY: Under normal conditions, motor evoked potentials (MEPs) elicited by
      transcranial magnetic stimulation increase in amplitude if the subject exercises
      the examined muscle immediately before recording. The authors examined the effect
      of nonfatiguing exercise on the amplitude of MEPs on 42 psychiatric, medicated
      inpatients (14 with depression, 14 with schizophrenia, and 14 with mania)
      compared with 14 healthy control subjects. For each subject, a total of 50
      baseline and 50 postexercise MEPs were recorded. The mean (+/- standard
      deviation) postexercise MEP facilitation, expressed as a percentage of mean
      baseline values, was significantly lower (p </= 0.02) in all three patient groups
      (148 +/- 91% in the depressed, 107 +/- 43% in the schizophrenic, and 143 +/- 63%
      in the manic patients) compared with the control subjects (268 +/- 223%). There
      was no clear evidence that psychotropic medication could be fully responsible for
      the modified MEP response to exercise, but the degree to which they were
      responsible is impossible to assess. These findings indicate that the reduced
      postexercise MEP facilitation is not related to any particular psychiatric
      illness, but rather that it represents a suppressed reaction of cortical
      excitability shared by patients with either depression, mania, or schizophrenia.
      The authors propose that, despite the lack of specificity, the study of
      postexercise MEP alterations could be useful in the neurophysiologic evaluation
      of motor cortex excitability in some psychiatric illnesses, except in those
      patients who may have diminished somatosensory input associated with voluntary
      muscle contraction resulting in decreased cortical excitability.

PMID- 12226570
TI  - H-reflex recovery curves differentiate essential tremor, Parkinson's disease, and
      the combination of essential tremor and Parkinson's disease.
AB  - The purpose of this study was to examine H-reflex parameters among the
      pathophysiologic conditions of essential tremor (ET), Parkinson's disease (PD),
      combined essential tremor with Parkinson's disease (ETPD), and a control group. H
      reflex latencies, amplitude of maximum H-reflex to maximum M-response ratio
      (H:M), vibration H-reflex to control H-reflex (Hv:Hc), and H-reflex recovery
      curves (HRRCs) were recorded and compared between a control group and patient
      groups with ET, early-stage PD, and with ETPD. No statistically or clinically
      significant differences were found between the patient groups and the control
      group for latency, H:M ratio, or Hv:Hc ratio. Significantly greater ratio values
      were observed for the PD group over the other groups for the HRRC tests at each
      interstimulus interval between 200 and 300 msec (p < 0.05), but values were not
      different between PD and ETPD patients for intervals between 350 and 1,000 msec.
      Patients with ET, PD, and ETPD apparently have different underlying pathologies.
      HRRC tests do not distinguish ET patients from normal, but differentiates
      specifically between PD and ETPD, and normal individuals. HRRC testing may be a
      useful method for evaluating pathologies between ET, PD, and ETPD patients.

PMID- 12226579
TI  - Making informed consent meaningful: a state-of-the-art conference.

PMID- 12226580
TI  - Enhancing protections for human participants in clinical and health services
      research: a continuing process.
AB  - The authors provide brief information about the Department of Veterans Affairs
      (VA) and the Veterans Health Administration, to establish an understanding of
      this large, multifaceted organization. They then offer an overview of the VA's
      Office of Research and Development, with particular emphasis on recent and
      ongoing efforts to enhance protection of the rights of human participants in
      clinical research. The authors discuss various policies and regulations intended
      to protect human participants in any type of VA research. The protection of human
      research participants must be a major concern for all researchers. Patients
      should be well informed about the scope of the research and what their
      participation entails, and there should be no question as to the voluntariness of
      their consent. Making sure that these standards are met for each and every
      veteran who participates in VA research is of the utmost importance.

PMID- 12226581
TI  - How changes in health care practices, systems, and research challenge the
      practice of informed consent.
AB  - Informed consent has been the central model for ethical decision making in
      clinical care and research. The goal of informed consent is to protect the right
      of a competent person to make his or her own health care decisions based on
      personal values and goals. But changes in health care practices, systems, and
      research have challenged this well-established goal. This paper examines these
      changes to show that decisions about care and research directed to individual
      patients rely more and more upon a population perspective. As a result, efforts
      to promote patient choice should attend to the ethical decision-making processes
      of institutions that create and sustain this perspective.

PMID- 12226582
TI  - Enrolling decisionally impaired adults in clinical research.
AB  - Progress in diagnosing, treating, and preventing medical conditions that impair
      decision-making abilities depends on clinical research involving individuals who
      may be either unable to or have diminished ability to give informed consent. Such
      research, however, raises ethical concern and controversy about the potential
      exploitation of these vulnerable individuals. This article addresses a range of
      ethical and practical issues concerning the enrollment of adults who are
      decisionally impaired, and those at risk of becoming so, in clinical research.
      These include (1) the relationship of decision-making capacity to competence, and
      the framework for determining competence in adults receiving clinical care and
      making treatment decisions for those who lack competence; (2) the differences
      between clinical practice and clinical research that influence the criteria for
      permissible research involving incompetent adults and the applicability of the
      framework guiding treatment decisions to clinical research decisions; and (3) the
      regulatory framework developed to guide the ethical participation of children in
      research and its applicability to determining the scope and limits of research
      with incompetent adults.

PMID- 12226584
TI  - Is information always a good thing? Helping patients make "good" decisions.
AB  - In most cases, patient preferences are crucial in making good health care
      decisions. For example, choices between chemotherapy and radiation treatment
      usually hinge on trade-offs that only patients can decide about. In recognition
      of the importance of patient preferences in clinical decisions, health services
      researchers have begun developing decision aids to help patients understand
      complex medical information. But these decision aids might lead to "bad choices"
      choices that are inconsistent with people's stated preferences. In this paper,
      the author provides examples of how people make inconsistent medical decisions,
      and briefly discusses future directions for exploring ways of structuring
      information so that patients are less likely to make inconsistent choices.

PMID- 12226583
TI  - Improving informed consent: insights from behavioral decision research.
AB  - BACKGROUND: With publication of The Belmont Report concerning ethical principles,
      informed consent gained explicit guidelines for the protection of human subjects
      of research. However, there is still little evidence about how well informed
      consent works to assist patients to reach informed decisions about research
      participation. OBJECTIVE: To review behavioral decision theory and research to
      identify implications for informed consent. RESEARCH DESIGN: Traditional
      literature review and hand search of literature were used. RESULTS: Psychological
      research on biases and heuristics identifies cognitive biases in information
      processing (selection and interpretation of risks and benefits) that have
      implications for improving the informing process. A growing literature on patient
      decision aids provides evidence for the feasibility of more fully informing
      patients, and includes examples of "debiasing" procedures (to improve information
      comprehension and consent). CONCLUSIONS: Informing and consenting involve
      conceptually different challenges concerning effectiveness versus values.
      Debiasing techniques need to be developed and empirically tested to determine
      their effectiveness in informing patients. Consenting involves both social and
      individual values. Appealing to altruism when summarizing the goals of research
      may increase research participation and does not necessarily violate
      voluntariness of informed consent. Additional research is needed to determine
      when information-processing biases occur problematically in health-related
      informed consent, and whether appealing to altruism increases research
      participation.

PMID- 12226585
TI  - The decision dynamics of clinical research: the context and process of informed
      consent.
AB  - This article explores the neglected dimensions of informed consent. In such
      documents as the that govern clinical research, it is explicitly stated that
      informed consent is a process, not a form to be signed. However, virtually all
      research on informed consent has proceeded as if informed consent is an event
      similar to a Miranda warning. The authors review what is known about the process
      of informed consent and ask what questions must be explored if the dynamics of
      the clinical decision-making process are to be better understood. Their
      investigation takes place in two parts. First, the authors survey what is known
      or not known about the effect and influence of two major parties to the decision
      making process (ie, support groups in which the subject participates and the
      subject's primary care physician). Second, they focus on the cultural and
      demographic factors that contribute to the subject's identity. Although they do
      not propose that informed consent must become a complicated and burdensome
      process, they stress that understanding the process in any meaningful way will
      mean that one must understand these various influences to get beyond the
      voluminous, but often facile, research that has characterized work on informed
      consent.

PMID- 12226586
TI  - The therapeutic misconception: problems and solutions.
AB  - BACKGROUND: The therapeutic misconception occurs when a research subject fails to
      appreciate the distinction between the imperatives of clinical research and of
      ordinary treatment, and therefore inaccurately attributes therapeutic intent to
      research procedures. The therapeutic misconception is a serious problem for
      informed consent in clinical research. OBJECTIVES: This paper analyzes the nature
      and origins of the therapeutic misconception and suggests some ways in which
      researchers can overcome this problem when obtaining a subject's consent to
      participation in research. RESEARCH DESIGN: A conceptual analysis of informed
      consent to research and a review of the empirical literature are undertaken.
      RESULTS: Research and clinical care involve different standards for how the
      patient/subject is to be treated. The confusion of the two often leads to
      profound misunderstandings on the part of the patient/subject. DISCUSSION: A
      method for describing to patients/subjects the differences between research and
      treatment is proposed as a potential solution to the therapeutic misconception.
      Research is needed to determine whether this or any other change in the nature of
      the disclosure is effective in reducing the therapeutic misconception.

PMID- 12226587
TI  - Obtaining voluntary consent for research in desperately ill patients.
AB  - Voluntary informed consent is a hard problem--one that inheres in the domain of
      research. The standard definition requires four criteria for consent to be
      morally valid: disclosure, understanding, voluntariness, and competence. These
      standards apply across the continuum of activities that comprise research. This
      paper concentrates on consent for the desperately sick, for whom enrollment in a
      research trial represents the last best hope of rescue. The literature indicates
      that many of these subjects enroll in research on the basis of feelings of hope
      or trust. This finding bypasses the careful weighing of risks and benefits that
      the model of informed consent is based upon. This paper explores how the
      requirements of candor need to be balanced with those of kindness.

PMID- 12226588
TI  - Voluntariness of consent for research: an empirical and conceptual review.
AB  - This article explores the vulnerability of research subjects either to undue
      influence or to coercion. The authors present a brief review of the requirement
      for voluntariness in research, and what is known about research participation.
      They then examine characteristics of potential subjects, researchers, researcher
      actions, and the research setting that can influence the voluntariness of
      subject's decisions to participate. Throughout the paper, empirical work that
      relates to voluntariness is used to illustrate the conceptual material.
      Voluntariness is viewed as an issue of self-control. Threats to voluntariness can
      arise from vulnerabilities of potential subjects as well as from characteristics
      of the researcher, the researcher's acts, and the research setting. Moral
      concerns about potential influences may be assessed by the likelihood that they
      will control or dominate a potential subject's decision to participate in
      research. Policy responses may be appropriate where the probability of control is
      too high.

PMID- 12226589
TI  - Disaster preparedness--the courage to respond.

PMID- 12226590
TI  - Attack on America: children's reactions and parents' responses.
AB  - INTRODUCTION: When disaster strikes, as it did September 11, 2001, children react
      to both the actual event and their parents' distress. The purpose of this study
      was to find out how children were affected by these recent events and how parents
      responded to their children's concerns. This study is a sequel to a previous
      study on parents' and children's perceptions to the President Clinton situation
      and the Starr Report. METHOD: Eighty-eight school-aged children and 51 parents
      were recruited for this descriptive, qualitative study that used community-based
      snowball sampling. Parents and children were asked a series of questions about
      the attacks on the World Trade Center and Pentagon, including how they heard
      about it and how it made them feel. RESULTS: Children's responses indicated
      feelings of fear about their safety and their future; wanting to take revenge;
      feeling sad and disappointed; and empathy for the victims. Parents realized they
      had to comfort their children in spite of their own feelings of dismay. Many
      parents reported difficulty in reacting to their child's concerns regarding
      fairness and justice. DISCUSSION: Pediatric nurse practitioners need to
      understand parents' and children's responses to such events in order to provide
      optimal health care, support, and counseling within the context of normal growth
      and development.

PMID- 12226591
TI  - Mental health worries, communication, and needs in the year of the U.S. terrorist
      attack: national KySS survey findings.
AB  - INTRODUCTION: To reduce the escalating rate of mental health/psychosocial
      morbidities in children and adolescents, NAPNAP initiated a new national campaign
      entitled Keep your children/yourself Safe and Secure (KySS). The objective of the
      first phase of this campaign was to conduct a national survey to assess the
      mental health knowledge, attitudes, worries, communication, and needs for
      intervention of children/teens, parents, and pediatric health care providers.
      This first report from the KySS survey describes the child/teen and parental
      findings. METHODS: A cross-section of 621 children/teens and 603 of their parents
      from 24 states completed the KySS survey during visits to their primary health
      care providers. RESULTS: The five greatest worries of both children/teens and
      their parents included knowing how to cope with stressful things in their lives,
      anxiety, depression, parent-child relationships, and problems with self-esteem.
      The majority of children/teens and their parents reported that they do not talk
      to their primary care providers about these issues. Participants expressed a
      multitude of needs and suggestions regarding how to better recognize, prevent,
      and deal with mental health problems. CONCLUSION: Opportunities must be created
      for children/teens and their parents to communicate their mental health worries
      and needs to each other and to their pediatric primary care providers to
      facilitate earlier diagnosis and treatment of mental health problems.
      Interventions are urgently needed to assist children and teens in coping with the
      multitude of stressors related to growing up in today's society.

PMID- 12226592
TI  - The aftermath of violence: children, disaster, and posttraumatic stress disorder.
AB  - Terrorist attacks, situations of armed conflict, and all forms of catastrophe tax
      our abilities to cope, understand, and respond. Because of their developmental
      status, children are even more emotionally vulnerable to the devastating effects
      of a disaster. When tragedy strikes a family, community, or the nation, helping
      children cope and regain a sense of safety is critical. A child with
      posttraumatic stress disorder (PTSD) develops symptoms such as intense fear,
      disorganized and agitated behavior, emotional numbness, anxiety, or depression
      after being directly exposed to or witnessing an extreme traumatic situation
      involving threatened death or serious injury. Victims of repeated abuse or
      children who live in violent neighborhoods or war zones, or who have witnessed
      extensive media coverage of violent events, may experience PTSD.

PMID- 12226593
TI  - Impact of the threat of war on children in military families.
AB  - The potential for war is a pervasive threat to the security and family structure
      of children in military families. This study compared children of active-duty,
      reserve, and civilian families with respect to their perceptions of war, origin
      of fears related to war, levels of manifest anxiety, coping strategies, and
      projection of emotional problems in human figure drawings.

PMID- 12226594
TI  - Anxiety disorders in children: intervention strategies for the primary care
      setting.

PMID- 12226595
TI  - Management of patients exposed to biologic weapons.

PMID- 12226596
TI  - Research on the impact of the threat of war on children in military families:
      where do we go from here?

PMID- 12226597
TI  - Bioterrorism, children, and the United States' health and security.

PMID- 12226598
TI  - Handling children's grief at the first anniversary.

PMID- 12226599
TI  - When terrible things happen: a parent's guide to talking with their children.

PMID- 12226600
TI  - Ask us. Cold nickel-titanium archwire.

PMID- 12226602
TI  - ADA research arm provides model for specialty.

PMID- 12226603
TI  - Polymerization of orthodontic resin cement with light-emitting diode curing
      units.
AB  - Commercially available light-emitting diode (LED) light-curing units recently
      have been introduced to the dental products market. No published studies have
      evaluated the adequacy of cure of commercially available LEDs. The purpose of
      this study was to compare the shear bond strength of orthodontic brackets bonded
      to teeth with conventional halogen-based light-curing units and commercially
      available LED curing units. Two LED light-curing units (LumaCure and VersaLux)
      and 2 halogen-based light-curing units (Optilux 501 and ProLite) were tested. One
      hundred standard metal orthodontic brackets were bonded to extracted human third
      molars with a light-cured adhesive system. The specimens were divided into 4
      groups of 25 teeth each. In each group, the brackets were cured for 40 seconds
      with a different light-curing unit. The specimens were stored in water at 37
      degrees C for 24 hours and then tested in shear with an Instron universal testing
      machine at a crosshead speed of 1 mm/min until the brackets debonded. One-way
      analysis of variance detected no differences in bond strength between the 4
      groups (P =.78). Chi-square analysis detected no difference in the adhesive
      remnant index scores of the 4 groups (P =.89). Under the conditions of this
      study, the LED light-curing units bonded brackets to etched tooth enamel as well
      as the halogen-based light-curing units. Additional clinical studies are
      necessary before routine use of commercial LED light-curing units can be
      recommended.

PMID- 12226604
TI  - Comparative bond strength of brackets cured using a pulsed xenon curing light
      with 2 different light-guide sizes.
AB  - Light curing of composite resin material beneath orthodontic brackets is common
      in clinical orthodontics. Experiences with composite resins and high-intensity
      lights indicate some advantages to staged curing of the composite. In this study,
      the shear/peel bond strength of orthodontic brackets bonded to bovine enamel and
      cured with a pulsed xenon plasma arc light was compared with that of bonds cured
      with a conventional tungsten-quartz-halogen light and a nonpulsed xenon plasma
      arc light. The pulsed light provided less light energy than the nonpulsed lights.
      A small and a larger light-guide tip were used with the pulsed xenon plasma arc
      light. Three different orthodontic composite resin adhesives were tested with
      each light. The pulsed xenon plasma arc light resulted in either the same or
      decreased shear/peel bond strength when compared with the nonpulsed lights. There
      appeared to be no advantage to the use of a pulsed xenon plasma arc light in
      bonding orthodontic brackets. Results from using either a small or a large light
      guide tip varied with the adhesive tested.

PMID- 12226606
TI  - Comparison of bond strength between simple foil mesh and laser-structured base
      retention brackets.
AB  - The aims of the current study were to evaluate the bond strength of a new
      metallic orthodontic bracket with a laser structured base (Discovery, Dentaurum,
      Ispringen, Germany), and its effects on the site of bond failure and on the
      behavior of the enamel after debonding. One hundred and twenty recently extracted
      human premolars were bonded with 1 of 2 types of mechanical interlock base metal
      brackets: a standard system with a simple foil mesh pad (Minitrim, Dentaurum) and
      the Discovery bracket. A resin-based, chemically activated bonding system, No-mix
      (Dentaurum), was used as the adhesive system in this trial. The teeth were
      immersed in normal saline solution at 37 degrees C for 7 days before debonding
      and were randomly assigned to different subgroups. A testing machine was used to
      evaluate tensile and fatigue bond strengths for both brackets. After debonding,
      the amount of residual adhesive on the bracket and enamel detachment were
      assessed according to the adhesive remnant index (ARI) and the enamel detachment
      index (EDI) with a scanning electron microscope and an energy dispersive X-ray
      spectrometer. The scores obtained from the ARI and the EDI showed that the laser
      structured base brackets had a significantly higher bond strength (mean +/- SD:
      17.1 +/- 0.7 MPa) that was 2 times higher than that observed with the simple foil
      mesh brackets (mean +/- SD: 8.7 +/- 1.4 MPa) (P <.001). Bond failure with the
      laser structured base was at the enamel-adhesive interface with an ARI score of 3
      in 80% of the teeth, and bond failure with the simple foil mesh base was at the
      bracket-adhesive interface with an ARI score of 0 in 75% of the teeth. A small
      area, with less than 10% of the enamel damaged (1 on the EDI) and 1.5 microm in
      thickness, was observed for both brackets. The laser structured base bracket's
      bond strength was double that of the simple foil mesh bracket but was equally
      safe and did not induce significant enamel detachment.

PMID- 12226605
TI  - The effects of argon laser irradiation on enamel decalcification: An in vivo
      study.
AB  - Enamel decalcification is a significant problem in orthodontic patients. The
      argon laser has been shown to reduce decalcification during an acidic challenge
      in vitro. The purpose of this study was to investigate the in vivo effects of
      argon laser irradiation on enamel decalcification during orthodontic treatment.
      Nine volunteers whose treatment plans included 4 first premolar extractions were
      enrolled in the study. The 36 extracted premolars were assigned to 1 of the
      following 4 groups: group 1, control group with no treatment; group 2 (pumice
      laser), teeth were pumiced for 3 seconds and treated with a 325 mW, 5-mm diameter
      laser beam for 60 seconds; group 3 (pumice-etch-laser), teeth were pumiced for 3
      seconds, acid-etched with 30% phosphoric acid for 30 seconds, and treated for 60
      seconds with laser; and group 4 (laser only), teeth were treated for 60 seconds
      with laser. A specially designed (oversized) orthodontic band was fitted on each
      of the premolars to create a pocket for decalcification. The bands were cemented
      in place for 5 weeks. After extraction, the teeth were sectioned and examined
      under polarized light microscopy. Images of lesions were digitally analyzed and
      measured. Average lesion depths were calculated from 3 depth measurements
      recorded 10 microm apart. Average lesion area was calculated with the aid of
      imaging analysis software. Data were analyzed with analysis of variance (P <.05)
      and Student t tests. Significant differences were found in lesion depth (P <.001)
      and lesion area (P <.01) among the 4 test groups. The average lesion depths were
      15.93 +/- 9.31 microm (control), 6.45 +/- 8.70 microm (pumice-laser), 1.71 +/-
      4.82 microm (pumice-etch-laser), and 1.34 +/- 3.80 microm (laser only). The
      average lesion areas were 1028.67 +/- 725.68 microm (2) (control), 555.49 +/-
      948.20 microm (2) (pumice-laser), 79.91 +/- 226.03 microm (2) (pumice-etch
      laser), and 55.71 +/- 157.59 microm (2) (laser only). The average lesion depth in
      the laser-only group was reduced by 94.1% and the average lesion area was reduced
      by 94.4% when compared with the control group. In the pumice-etch-laser group,
      the average lesion depth was reduced by 89.1% and the average lesion area was
      reduced by 92.2% when compared with the control group. There were no significant
      differences in lesion depth and lesion area between maxillary and mandibular
      teeth (P <.06 and P <.08, respectively) and between the teeth on the right and
      left sides (P <.68 and P <.55, respectively). These results show that argon laser
      irradiation is effective in reducing enamel decalcification during orthodontic
      treatment. Pumicing and etching do not appear to reduce the effect of laser on
      enamel solubility.

PMID- 12226607
TI  - Bond strength comparison of moisture-insensitive primers.
AB  - The objective of this in vitro bonding study was to evaluate the effectiveness of
      2 moisture-insensitive primers, Assure (Reliance Orthodontic Products, Itasca,
      Ill) and MIP (3M Unitek, Monrovia, Calif) compared with a control hydrophobic
      primer, Transbond XT (3M Unitek). Six groups of 40 premolars were acid etched and
      bonded using metal orthodontic brackets with the following in vitro protocols:
      (1) Transbond XT primer and adhesive applied to a noncontaminated surface; (2)
      Assure primer applied after saliva contamination; (3) MIP primer applied after
      saliva contamination; (4) Assure primer reapplied after saliva contamination; (5)
      MIP reapplied after saliva contamination; and (6) Assure adhesive applied after
      saliva contamination of the primer. All bonded specimens were stored in deionized
      water at 37 degrees C for 30 days and thermocycled for 24 hours before debonding.
      Brackets were debonded using a shear-peel load on a testing machine, bond
      strength was measured in megapascals, and bond failure was analyzed by using the
      adhesive remnant index. In vitro shear-peel bond strengths were acceptable for
      all groups, and the bond strengths for Assure and MIP were not significantly
      affected by saliva contamination. The mean shear-peel bond strength of the
      control (14.82 MPa) was significantly higher (P <.001) than the contaminated
      groups with the exception of MIP group 5 (14.02 MPa). The values of the Assure
      primer and adhesive were less than the MIP primer and its respective adhesive;
      however, the hydrophilic Assure adhesive resin applied to a saliva-contaminated
      surface had acceptable bond strength. Bond failure analysis (adhesive remnant
      index) mainly showed adhesive bond failures. An increased frequency of enamel
      fractures at debond was noted, with the control group (1) and the MIP groups (3
      and 5) having 22.5%, 12.5%, and 15%, respectively. The Assure groups had no
      enamel fractures.

PMID- 12226608
TI  - Bonding of stainless steel brackets to enamel with a new self-etching primer.
AB  - The purpose of this study was to measure the shear bond strength of stainless
      steel brackets bonded to enamel in vitro with a recently developed self-etching
      primer (Transbond Plus Self Etching Primer, 3M Unitek, Monrovia, Calif). Forty
      eight extracted human teeth were obtained and randomly divided into 4 groups of
      12: (1) control group with a conventional etchant and separate primer, (2)
      experimental group with the self-etching primer, left for 15 seconds before
      bonding, (3) same as group 2, but with the primer left for 2 minutes before
      bonding, (4) same as group 2, but with the primer left for 10 minutes before
      bonding. For each group, stainless steel brackets were mounted onto the prepared
      enamel, stored for 24 hours at 37 degrees C, and tested in a testing machine with
      a crosshead speed of 1 mm/min. There was no significant difference in the bond
      strength between the 4 groups as determined by analysis of variance (ANOVA) (P
      <.05). Under the conditions of these experiments, a 10-minute delay in bonding
      after application of the self-etching primer might not be deleterious to
      adhesion.

PMID- 12226609
TI  - Bond failure of a no-mix adhesive during orthodontic treatment.
AB  - Bond failure of a no-mix adhesive was evaluated in 320 patients followed
      longitudinally during orthodontic treatment. Factors evaluated were the patient's
      gender, the complexity of the appliance, the bond site location, initial
      crowding, and caries development. The overall bond failure rate was 7.2%. Bond
      failures were significantly higher in the mandible, with the second premolars
      showing the highest prevalence (23%) (P <.001). There were significantly higher
      bond failure rates in boys than in girls (P <.05). There was a significant
      negative correlation between initial crowding and bond failure. Increased white
      spot lesions during treatment and complex appliance design were significantly
      correlated with high bond failure rates.

PMID- 12226611
TI  - Evaluation of antimicrobial properties of orthodontic composite resins combined
      with benzalkonium chloride.
AB  - An antimicrobial agent, benzalkonium chloride (BAC), was added to a chemically
      cured composite resin, and the antimicrobial benefits and physical properties of
      the modified composite were evaluated. BAC was added to Reliance Phase II
      composite to create modified composites with BAC concentrations ranging from 0.25
      to 2.50 wt%. Specimen disks of the modified composite were incubated with
      Streptococcus mutans for 48 hours, and an agar disk diffusion assay was used to
      measure zones of bacterial inhibition. Larger disks were suspended in brain-heart
      infusion medium containing 2 x 10(4) colony-forming units/mL Streptococcus
      sobrinus (10 mL, 2 wt% sucrose, 24 hours) to measure bacterial adherence to the
      adhesive; adherent cells were removed from the surface with 1 N NaOH, and the
      optical density of the cells was measured at 550 nanometers. Traction hooks were
      bonded to bovine teeth with the modified composite, and tensile bond strength was
      evaluated with a universal testing machine. Diametral tensile stress was also
      measured. The modified composite samples showed that antimicrobial activity
      increased with higher BAC content; no antimicrobial activity was measured for the
      original compound in either the disk diffusion or the bacterial adherence test.
      There were no significant differences (P <.05) in either tensile bond strength or
      diametral tensile stress among the modified composite groups and the original
      product. The incorporation of BAC in composite material added antimicrobial
      properties to the original compound without altering its mechanical properties.

PMID- 12226610
TI  - Shear bond strength of rebonded mechanically retentive ceramic brackets.
AB  - The purpose of this study was to evaluate the bond strength of rebonded
      mechanically retentive ceramic brackets. Twenty new and 100 sandblasted rebonded
      ceramic brackets (Clarity, 3M Unitek, Monrovia, Calif) were bonded to 120
      extracted human premolars with composite resin and divided into 6 equal groups
      according to how the bracket bases were treated: (1) new brackets, (2)
      rebonded/sandblasted, (3) rebonded/sandblasted/sealant, (4)
      rebonded/sandblasted/hydrofluoric acid (HF), (5) rebonded/sandblasted/HF/sealant
      on bracket base, and (6) rebonded/sandblasted/silane. Shear bond strength of each
      sample was tested with a testing machine. Results showed that the new brackets
      group had the highest mean strength (15.66 +/- 7.05 megapascals [MPa]), followed
      by the rebonded/sandblasted/sealant group (7.65 +/- 5.62 MPa), the
      rebonded/sandblasted/silane group (5.94 +/- 5.33 MPa), the rebonded/sandblasted
      group (2.97 +/- 2.29 MPa), the rebonded/sandblasted/HF group (1.22 +/- 1.66 MPa),
      and the rebonded/sandblasted/HF/sealant group (0.82 +/- 1.16 MPa). Statistical
      analysis showed that only the rebonded/sandblasted/sealant group was comparable
      with the new brackets group in bond strength (P >.05). It was concluded that in
      the process of rebonding mechanically retentive ceramic brackets, (1) new
      brackets have the highest mean bond strength when compared with rebonded
      brackets, (2) the bond strength of sandblasted rebonded brackets with sealant is
      not significantly different from new brackets, (3) silane does not increase bond
      strength of rebonded brackets significantly, and (4) HF treatment on sandblasted
      rebonded brackets significantly decreases bond strength.

PMID- 12226612
TI  - Effect of archwire size and material on the resistance to sliding of self
      ligating brackets with second-order angulation in the dry state.
AB  - When paired with a particular self-ligating bracket design, the material and the
      geometric characteristics of an archwire influence its resistance to sliding.
      Four designs of self-ligating brackets (1 with a slide, 3 with clips) were
      coupled with 5 types of archwires: 14-mil round austenitic nickel-titanium, 16 x
      22-mil rectangular austenitic nickel-titanium, 19 x 25-mil rectangular austenitic
      nickel-titanium, 19 x 25-mil rectangular martensitic nickel-titanium, and 19 x 25
      mil rectangular stainless steel. The resistance to sliding (RS) of each archwire
      bracket couple was measured at second-order angles between -9 degrees and 9
      degrees. Interbracket distances of 8 and 18 mm between the test bracket and the
      adjacent brackets mimicked closure of a premolar extraction. When clearance
      exists, the RS is negligible for self-ligating brackets with slides coupled to
      any size of wire as well as for those with clips when coupled to wires that do
      not contact the clip. Once the wire attains a certain size and contacts the clip,
      the RS depends on the archwire size, the bracket design, and the materials of the
      couple. When coupled with the 16 x 22-mil wire, the brackets with clips applied
      normal forces ranging from a low of 5.6 centi-Newtons (cN) (1 cN = 1 g) to a high
      of 230 cN. When clearance disappears, the RS increased proportionally with the
      second-order angle. The 19 x 25-mil stainless steel wires, which were the most
      stiff, increased at rates between 75 and 84 cN/degree; the 14-mil austenitic
      nickel-titanium wires, which were the least stiff, increased at rates from 2.6 to
      5.4 cN/degree. The treatment objectives for a particular patient at a specific
      stage should determine the appropriate archwire-bracket combination.

PMID- 12226613
TI  - Involvement of nitric oxide in orthodontic tooth movement in rats.
AB  - Nitric oxide (NO) is an important regulatory molecule in bone formation and
      resorption. The purpose of this study was to examine the role of NO in
      orthodontic tooth movement in rats. We used specific inhibitors of NO synthases
      (NOS). Upper first molars of 9-week-old male Wistar rats were moved buccally for
      21 days. The local administration of N(G)-nitro-L-arginine methyl ester. HCl (L
      NAME), a general inhibitor of NOS activity, significantly reduced tooth movement.
      On the other hand, N(6)-(1-iminoethyl)-L-lysine. 2HCl (L-NIL), a selective
      inhibitor of the inducible isoform of NOS, had no effect. These results suggest
      that NO is an important biochemical mediator in the response of periodontal
      tissue to orthodontic force and is produced primarily through the activity of
      constitutive NOS.

PMID- 12226614
TI  - A new approach to correction of crowding.

PMID- 12226615
TI  - Treatment of an adult patient with severely crowded bimaxillary protrusive Class
      II malocclusion with atypical extractions.

PMID- 12226616
TI  - In search of anatomic truth: 3-dimensional digital modeling and the future of
      orthodontics.

PMID- 12226617
TI  - Litigation, legislation, and ethics: punitive damages.

PMID- 12226619
TI  - The physics imbalance.

PMID- 12226620
TI  - Chemistry plans a structural overhaul.

PMID- 12226621
TI  - A unified political trajectory.

PMID- 12226622
TI  - Arrest of AIDS activist underlines China's impending HIV crisis.

PMID- 12226623
TI  - Security worries stifle report on agricultural bioterror.

PMID- 12226624
TI  - India's scientists agonize over fall in publication rate.

PMID- 12226625
TI  - Patent office plan to beat its backlog elicits cool response.

PMID- 12226626
TI  - EU ponders joint action on cancer.

PMID- 12226627
TI  - NIH pledges cash for global protein database.

PMID- 12226628
TI  - Blood banks call for calm over virus scare.

PMID- 12226629
TI  - Universities urged to get with IT for biology.

PMID- 12226630
TI  - Looting and vandalism threaten Afghanistan's seed distribution.

PMID- 12226631
TI  - Early Einstein manuscript set to make a relative fortune.

PMID- 12226632
TI  - Fruitful meeting between the Pope and Montagnier.

PMID- 12226633
TI  - An out of body experience.

PMID- 12226634
TI  - A window of opportunity.

PMID- 12226635
TI  - Can commercial protection be good for research?

PMID- 12226636
TI  - Industry scientists look for benefits, not risks.

PMID- 12226637
TI  - Public-access group supports PubMed Central.

PMID- 12226643
TI  - Matter all in the mind.

PMID- 12226644
TI  - Casimir force changes sign.

PMID- 12226645
TI  - DNA repair: right on target with ubiquitin.

PMID- 12226646
TI  - The missing link.

PMID- 12226647
TI  - Global change: oceanic action at a distance.

PMID- 12226649
TI  - Optics: the light fantastic.

PMID- 12226650
TI  - Cancer: stuck at first base.

PMID- 12226652
TI  - Baked Alaska.

PMID- 12226651
TI  - Ecology: oceans under the macroscope.

PMID- 12226653
TI  - Mexican waves in an excitable medium.
AB  - The Mexican wave, or La Ola, which rose to fame during the 1986 World Cup in
      Mexico, surges through the rows of spectators in a stadium as those in one
      section leap to their feet with their arms up, and then sit down again as the
      next section rises to repeat the motion. To interpret and quantify this
      collective human behaviour, we have used a variant of models that were originally
      developed to describe excitable media such as cardiac tissue. Modelling the
      reaction of the crowd to attempts to trigger the wave reveals how this phenomenon
      is stimulated, and may prove useful in controlling events that involve groups of
      excited people.

PMID- 12226654
TI  - Biological pacemaker created by gene transfer.
AB  - The pacemaker cells of the heart initiate the heartbeat, sustain the circulation,
      and dictate the rate and rhythm of cardiac contraction. Circulatory collapse
      ensues when these specialized cells are damaged by disease, a situation that
      currently necessitates the implantation of an electronic pacemaker. Here we
      report the use of viral gene transfer to convert quiescent heart-muscle cells
      into pacemaker cells, and the successful generation of spontaneous, rhythmic
      electrical activity in the ventricle in vivo. Our results indicate that
      genetically engineered pacemakers could be developed as a possible alternative to
      implantable electronic devices.

PMID- 12226655
TI  - Metallurgy: high nickel release from 1- and 2-euro coins.
AB  - The amount of nickel is regulated in European products that come into direct and
      prolonged contact with human skin because this metal may cause contact allergy,
      particularly hand eczema. Here we show that 1- and 2-euro coins induce positive
      skin-test reactions in sensitized individuals and release 240-320-fold more
      nickel than is allowed under the European Union Nickel Directive. A factor
      contributing to this high release of nickel is corrosion due to the bimetallic
      structure of these coins, which generates a galvanic potential of 30-40 mV in
      human sweat.

PMID- 12226656
TI  - Nanometre-size products of uranium bioreduction.
AB  - One strategy that is being pursued to tackle the international problem of
      actinide contamination of soils, sediments and water is to use microbial activity
      to 'fix' these radionuclides into an insoluble form that cannot be readily
      dispersed. Here we show that uraninite (UO(2)) particles formed from uranium in
      sediments by bacterial reduction are typically less than 2 nanometres across and
      that the small size has important implications for uraninite reactivity and fate.
      Because these tiny particles may still be transported in an aqueous environment,
      precipitation of uranium as insoluble uraninite cannot be presumed to immobilize
      it.

PMID- 12226657
TI  - RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and
      SUMO.
AB  - The RAD6 pathway is central to post-replicative DNA repair in eukaryotic cells;
      however, the machinery and its regulation remain poorly understood. Two principal
      elements of this pathway are the ubiquitin-conjugating enzymes RAD6 and the MMS2
      UBC13 heterodimer, which are recruited to chromatin by the RING-finger proteins
      RAD18 and RAD5, respectively. Here we show that UBC9, a small ubiquitin-related
      modifier (SUMO)-conjugating enzyme, is also affiliated with this pathway and that
      proliferating cell nuclear antigen (PCNA) -- a DNA-polymerase sliding clamp
      involved in DNA synthesis and repair -- is a substrate. PCNA is mono
      ubiquitinated through RAD6 and RAD18, modified by lysine-63-linked multi
      ubiquitination--which additionally requires MMS2, UBC13 and RAD5--and is
      conjugated to SUMO by UBC9. All three modifications affect the same lysine
      residue of PCNA, suggesting that they label PCNA for alternative functions. We
      demonstrate that these modifications differentially affect resistance to DNA
      damage, and that damage-induced PCNA ubiquitination is elementary for DNA repair
      and occurs at the same conserved residue in yeast and humans.

PMID- 12226658
TI  - Magnetar-like X-ray bursts from an anomalous X-ray pulsar.
AB  - Anomalous X-ray pulsars (AXPs) are a class of rare X-ray emitting pulsars whose
      energy source has been perplexing for some 20 years. Unlike other X-ray emitting
      pulsars, AXPs cannot be powered by rotational energy or by accretion of matter
      from a binary companion star, hence the designation 'anomalous'. Many of the
      rotational and radiative properties of the AXPs are strikingly similar to those
      of another class of exotic objects, the soft-gamma-ray repeaters (SGRs). But the
      defining property of the SGRs--their low-energy-gamma-ray and X-ray bursts--has
      not hitherto been observed for AXPs. Soft-gamma-ray repeaters are thought to be
      'magnetars', which are young neutron stars whose emission is powered by the decay
      of an ultra-high magnetic field; the suggestion that AXPs might also be magnetars
      has been controversial. Here we report two X-ray bursts, with properties similar
      to those of SGRs, from the direction of the anomalous X-ray pulsar 1E1048.1 -
      5937. These events imply a close relationship (perhaps evolutionary) between AXPs
      and SGRs, with both being magnetars.

PMID- 12226659
TI  - Simultaneous micromanipulation in multiple planes using a self-reconstructing
      light beam.
AB  - Optical tweezers are commonly used for manipulating microscopic particles, with
      applications in cell manipulation, colloid research, manipulation of
      micromachines and studies of the properties of light beams. Such tweezers work by
      the transfer of momentum from a tightly focused laser to the particle, which
      refracts and scatters the light and distorts the profile of the beam. The forces
      produced by this process cause the particle to be trapped near the beam focus.
      Conventional tweezers use gaussian light beams, which cannot trap particles in
      multiple locations more than a few micrometres apart in the axial direction,
      because of beam distortion by the particle and subsequent strong divergence from
      the focal plane. Bessel beams, however, do not diverge and, furthermore, if part
      of the beam is obstructed or distorted the beam reconstructs itself after a
      characteristic propagation distance. Here we show how this reconstructive
      property may be utilized within optical tweezers to trap particles in multiple,
      spatially separated sample cells with a single beam. Owing to the diffractionless
      nature of the Bessel beam, secondary trapped particles can reside in a second
      sample cell far removed ( approximately 3 mm) from the first cell. Such tweezers
      could be used for the simultaneous study of identically prepared ensembles of
      colloids and biological matter, and potentially offer enhanced control of 'lab-on
      a-chip' and optically driven microstructures.

PMID- 12226660
TI  - Mechanical milling assisted by electrical discharge.
AB  - Mechanical milling is an effective technique for the preparation of fine metallic
      and ceramic powders and can also be used to drive a wide range of chemical
      reactions. Milling devices include planetary machines, attritors and vibrational
      mills; products include amorphous, nanocrystalline and quasicrystalline
      materials, supersaturated solid solutions, reduced minerals, high-surface-area
      catalysts and reactive chemicals. During milling, solid-solid, solid-liquid and
      solid-gas reactions are initiated through repeated deformation and fracture of
      powder particles. A separate materials synthesis and processing technique
      involves reacting a material in a gas atmosphere under an electrical discharge.
      Here we show that the application of low-current, high-voltage electrical
      impulses during milling can result in both faster reactions and new synthesis and
      processing routes. We demonstrate the effects of glow (cold) and spark (hot)
      discharge milling on particle fracture for brittle, low-conductivity materials
      and ductile metals. Glow discharge milling was found to promote solid-gas
      reactions whereas spark discharge milling promotes fast fracturing,
      recrystallization, mineral reduction and solid-solid reactions.

PMID- 12226661
TI  - Acceleration of rain initiation by cloud turbulence.
AB  - Vapour condensation in cloud cores produces small droplets that are close to one
      another in size. Droplets are believed to grow to raindrop size by coalescence
      due to collision. Air turbulence is thought to be the main cause for collisions
      of similar-sized droplets exceeding radii of a few micrometres, and therefore
      rain prediction requires a quantitative description of droplet collision in
      turbulence. Turbulent vortices act as small centrifuges that spin heavy droplets
      out, creating concentration inhomogeneities and jets of droplets, both of which
      increase the mean collision rate. Here we derive a formula for the collision rate
      of small heavy particles in a turbulent flow, using a recently developed
      formalism for tracing random trajectories. We describe an enhancement of inertial
      effects by turbulence intermittency and an interplay between turbulence and
      gravity that determines the collision rate. We present a new mechanism, the
      'sling effect', for collisions due to jets of droplets that become detached from
      the air flow. We conclude that air turbulence can substantially accelerate the
      appearance of large droplets that trigger rain.

PMID- 12226662
TI  - Macroecological patterns of phytoplankton in the northwestern North Atlantic
      Ocean.
AB  - Many issues in biological oceanography are regional or global in scope; however,
      there are not many data sets of extensive areal coverage for marine plankton. In
      microbial ecology, a fruitful approach to large-scale questions is comparative
      analysis wherein statistical data patterns are sought from different ecosystems,
      frequently assembled from unrelated studies. A more recent approach termed
      macroecology characterizes phenomena emerging from large numbers of biological
      units by emphasizing the shapes and boundaries of statistical distributions,
      because these reflect the constraints on variation. Here, I use a set of flow
      cytometric measurements to provide macroecological perspectives on North Atlantic
      phytoplankton communities. Distinct trends of abundance in picophytoplankton and
      both small and large nanophytoplankton underlaid two patterns. First, total
      abundance of the three groups was related to assemblage mean-cell size according
      to the 3/4 power law of allometric scaling in biology. Second, cytometric
      diversity (an ataxonomic measure of assemblage entropy) was maximal at
      intermediate levels of water column stratification. Here, intermediate
      disturbance shapes diversity through an equitable distribution of cells in size
      classes, from which arises a high overall biomass. By subsuming local
      fluctuations, macroecology reveals meaningful patterns of phytoplankton at large
      scales.

PMID- 12226663
TI  - Coding of smooth eye movements in three-dimensional space by frontal cortex.
AB  - Through the development of a high-acuity fovea, primates with frontal eyes have
      acquired the ability to use binocular eye movements to track small objects moving
      in space. The smooth-pursuit system moves both eyes in the same direction to
      track movement in the frontal plane (frontal pursuit), whereas the vergence
      system moves left and right eyes in opposite directions to track targets moving
      towards or away from the observer (vergence tracking). In the cerebral cortex and
      brainstem, signals related to vergence eye movements--and the retinal disparity
      and blur signals that elicit them--are coded independently of signals related to
      frontal pursuit. Here we show that these types of signal are represented in a
      completely different way in the smooth-pursuit region of the frontal eye fields.
      Neurons of the frontal eye field modulate strongly during both frontal pursuit
      and vergence tracking, which results in three-dimensional cartesian
      representations of eye movements. We propose that the brain creates this
      distinctly different intermediate representation to allow these neurons to
      function as part of a system that enables primates to track and manipulate
      objects moving in three-dimensional space.

PMID- 12226664
TI  - Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance
      to transformation.
AB  - Germline mutations in LKB1 (also known as STK11) are associated with Peutz
      Jeghers syndrome (PJS), a disorder with predisposition to gastrointestinal
      polyposis and cancer. PJS polyps are unusual neoplasms characterized by marked
      epithelial and stromal overgrowth but have limited malignant potential. Here we
      show that Lkb1(+/-) mice develop intestinal polyps identical to those seen in
      individuals affected with PJS. Consistent with this in vivo tumour suppressor
      function, Lkb1 deficiency prevents culture-induced senescence without loss of
      Ink4a/Arf or p53. Despite compromised mortality, Lkb1(-/-) mouse embryonic
      fibroblasts show resistance to transformation by activated Ha-Ras either alone or
      with immortalizing oncogenes. This phenotype is in agreement with the paucity of
      mutations in Ras seen in PJS polyps and suggests that loss of Lkb1 function as an
      early neoplastic event renders cells resistant to subsequent oncogene-induced
      transformation. In addition, the Lkb1 transcriptome shows modulation of factors
      linked to angiogenesis, extracellular matrix remodelling, cell adhesion and
      inhibition of Ras transformation. Together, our data rationalize several features
      of PJS polyposis--notably its peculiar histopathological presentation and limited
      malignant potential--and place Lkb1 in a distinct class of tumour suppressors.

PMID- 12226665
TI  - SINAT5 promotes ubiquitin-related degradation of NAC1 to attenuate auxin signals.
AB  - The plant hormone indole-3 acetic acid (IAA or auxin) controls many aspects of
      plant development, including the production of lateral roots. Ubiquitin-mediated
      proteolysis has a central role in this process. The genes AXR1 and TIR1 aid the
      assembly of an active SCF (Skp1/Cullin/F-box) complex that probably promotes
      degradation of the AUX/IAA transcriptional repressors in response to auxin. The
      transcription activator NAC1, a member of the NAM/CUC family of transcription
      factors, functions downstream of TIR1 to transduce the auxin signal for lateral
      root development. Here we show that SINAT5, an Arabidopsis homologue of the RING
      finger Drosophila protein SINA, has ubiquitin protein ligase activity and can
      ubiquitinate NAC1. This activity is abolished by mutations in the RING motif of
      SINAT5. Overexpressing SINAT5 produces fewer lateral roots, whereas
      overexpression of a dominant-negative Cys49 --> Ser mutant of SINAT5 develops
      more lateral roots. These lateral root phenotypes correlate with the expression
      of NAC1 observed in vivo. Low expression of NAC1 in roots can be increased by
      treatment with a proteasome inhibitor, which indicates that SINAT5 targets NAC1
      for ubiquitin-mediated proteolysis to downregulate auxin signals in plant cells.

PMID- 12226666
TI  - L23 protein functions as a chaperone docking site on the ribosome.
AB  - During translation, the first encounter of nascent polypeptides is with the
      ribosome-associated chaperones that assist the folding process--a principle that
      seems to be conserved in evolution. In Escherichia coli, the ribosome-bound
      Trigger Factor chaperones the folding of cytosolic proteins by interacting with
      nascent polypeptides. Here we identify a ribosome-binding motif in the amino
      terminal domain of Trigger Factor. We also show the formation of crosslinked
      products between Trigger Factor and two adjacent ribosomal proteins, L23 and L29,
      which are located at the exit of the peptide tunnel in the ribosome. L23 is
      essential for the growth of E. coli and the association of Trigger Factor with
      the ribosome, whereas L29 is dispensable in both processes. Mutation of an
      exposed glutamate in L23 prevents Trigger Factor from interacting with ribosomes
      and nascent chains, and causes protein aggregation and conditional lethality in
      cells that lack the protein repair function of the DnaK chaperone. Purified L23
      also interacts specifically with Trigger Factor in vitro. We conclude that
      essential L23 provides a chaperone docking site on ribosomes that directly links
      protein biosynthesis with chaperone-assisted protein folding.

PMID- 12226667
TI  - Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base
      damage.
AB  - Methylating agents generate cytotoxic and mutagenic DNA damage. Cells use 3
      methyladenine-DNA glycosylases to excise some methylated bases from DNA, and
      suicidal O(6)-methylguanine-DNA methyltransferases to transfer alkyl groups from
      other lesions onto a cysteine residue. Here we report that the highly conserved
      AlkB protein repairs DNA alkylation damage by means of an unprecedented
      mechanism. AlkB has no detectable nuclease, DNA glycosylase or methyltransferase
      activity; however, Escherichia coli alkB mutants are defective in processing
      methylation damage generated in single-stranded DNA. Theoretical protein fold
      recognition had suggested that AlkB resembles the Fe(ii)- and alpha-ketoglutarate
      dependent dioxygenases, which use iron-oxo intermediates to oxidize chemically
      inert compounds. We show here that purified AlkB repairs the cytotoxic lesions 1
      methyladenine and 3-methylcytosine in single- and double-stranded DNA in a
      reaction that is dependent on oxygen, alpha-ketoglutarate and Fe(ii). The AlkB
      enzyme couples oxidative decarboxylation of alpha-ketoglutarate to the
      hydroxylation of these methylated bases in DNA, resulting in direct reversion to
      the unmodified base and the release of formaldehyde.

PMID- 12226668
TI  - AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli.
AB  - The bacterial AlkB protein is known to be involved in cellular recovery from
      alkylation damage; however, the function of this protein remains unknown. AlkB
      homologues have been identified in several organisms, including humans, and a
      recent sequence alignment study has suggested that these proteins may belong to a
      superfamily of 2-oxoglutarate-dependent and iron-dependent oxygenases (2OG-Fe(ii)
      oxygenases). Here we show that AlkB from Escherichia coli is indeed a 2
      oxoglutarate-dependent and iron-dependent DNA repair enzyme that releases
      replication blocks in alkylated DNA by a mechanism involving oxidative
      demethylation of 1-methyladenine residues. This mechanism represents a new
      pathway for DNA repair and the third type of DNA damage reversal mechanism so far
      discovered.

PMID- 12226669
TI  - Comprehensive proteomic analysis of the human spliceosome.
AB  - The precise excision of introns from pre-messenger RNA is performed by the
      spliceosome, a macromolecular machine containing five small nuclear RNAs and
      numerous proteins. Much has been learned about the protein components of the
      spliceosome from analysis of individual purified small nuclear ribonucleoproteins
      and salt-stable spliceosome 'core' particles. However, the complete set of
      proteins that constitutes intact functional spliceosomes has yet to be
      identified. Here we use maltose-binding protein affinity chromatography to
      isolate spliceosomes in highly purified and functional form. Using nanoscale
      microcapillary liquid chromatography tandem mass spectrometry, we identify
      approximately 145 distinct spliceosomal proteins, making the spliceosome the most
      complex cellular machine so far characterized. Our spliceosomes comprise all
      previously known splicing factors and 58 newly identified components. The
      spliceosome contains at least 30 proteins with known or putative roles in gene
      expression steps other than splicing. This complexity may be required not only
      for splicing multi-intronic metazoan pre-messenger RNAs, but also for mediating
      the extensive coupling between splicing and other steps in gene expression.

PMID- 12226672
TI  - Reducing uncertainty about carbon dioxide as a climate driver.
AB  - The lack of an adequate ancient analogue for future climates means that we
      ultimately must use and trust climate models, evaluated against modern
      observation and our best geologic records of warm and cold climates of the past.
      Armed with an elevated confidence in the models, we will then be able to make
      reliable predictions of the Earth's response to our risky experiment with the
      climate system.

PMID- 12226673
TI  - The hydrologic cycle in deep-time climate problems.
AB  - Hydrology refers to the whole panoply of effects the water molecule has on
      climate and on the land surface during its journey there and back again between
      ocean and atmosphere. On its way, it is cycled through vapour, cloud water, snow,
      sea ice and glacier ice, as well as acting as a catalyst for silicate-carbonate
      weathering reactions governing atmospheric carbon dioxide. Because carbon dioxide
      affects the hydrologic cycle through temperature, climate is a pas des deux
      between carbon dioxide and water, with important guest appearances by surface ice
      cover.

PMID- 12226674
TI  - Links between climate and sea levels for the past three million years.
AB  - The oscillations between glacial and interglacial climate conditions over the
      past three million years have been characterized by a transfer of immense amounts
      of water between two of its largest reservoirs on Earth -- the ice sheets and the
      oceans. Since the latest of these oscillations, the Last Glacial Maximum (between
      about 30,000 and 19,000 years ago), approximately 50 million cubic kilometres of
      ice has melted from the land-based ice sheets, raising global sea level by
      approximately 130 metres. Such rapid changes in sea level are part of a complex
      pattern of interactions between the atmosphere, oceans, ice sheets and solid
      earth, all of which have different response timescales. The trigger for the sea
      level fluctuations most probably lies with changes in insolation, caused by
      astronomical forcing, but internal feedback cycles complicate the simple model of
      causes and effects.

PMID- 12226675
TI  - Ocean circulation and climate during the past 120,000 years.
AB  - Oceans cover more than two-thirds of our blue planet. The waters move in a global
      circulation system, driven by subtle density differences and transporting huge
      amounts of heat. Ocean circulation is thus an active and highly nonlinear player
      in the global climate game. Increasingly clear evidence implicates ocean
      circulation in abrupt and dramatic climate shifts, such as sudden temperature
      changes in Greenland on the order of 5-10 degrees C and massive surges of
      icebergs into the North Atlantic Ocean --events that have occurred repeatedly
      during the last glacial cycle.

PMID- 12226676
TI  - A satellite view of aerosols in the climate system.
AB  - Anthropogenic aerosols are intricately linked to the climate system and to the
      hydrologic cycle. The net effect of aerosols is to cool the climate system by
      reflecting sunlight. Depending on their composition, aerosols can also absorb
      sunlight in the atmosphere, further cooling the surface but warming the
      atmosphere in the process. These effects of aerosols on the temperature profile,
      along with the role of aerosols as cloud condensation nuclei, impact the
      hydrologic cycle, through changes in cloud cover, cloud properties and
      precipitation. Unravelling these feedbacks is particularly difficult because
      aerosols take a multitude of shapes and forms, ranging from desert dust to urban
      pollution, and because aerosol concentrations vary strongly over time and space.
      To accurately study aerosol distribution and composition therefore requires
      continuous observations from satellites, networks of ground-based instruments and
      dedicated field experiments. Increases in aerosol concentration and changes in
      their composition, driven by industrialization and an expanding population, may
      adversely affect the Earth's climate and water supply.

PMID- 12226677
TI  - Constraints on future changes in climate and the hydrologic cycle.
AB  - What can we say about changes in the hydrologic cycle on 50-year timescales when
      we cannot predict rainfall next week? Eventually, perhaps, a great deal: the
      overall climate response to increasing atmospheric concentrations of greenhouse
      gases may prove much simpler and more predictable than the chaos of short-term
      weather. Quantifying the diversity of possible responses is essential for any
      objective, probability-based climate forecast, and this task will require a new
      generation of climate modelling experiments, systematically exploring the range
      of model behaviour that is consistent with observations. It will be substantially
      harder to quantify the range of possible changes in the hydrologic cycle than in
      global-mean temperature, both because the observations are less complete and
      because the physical constraints are weaker.

PMID- 12226678
TI  - Towards objective probabalistic climate forecasting.

PMID- 12226679
TI  - Self-reported awareness and use of the International Classification of Diseases
      coding of inflammatory bowel disease services by Ontario physicians.
AB  - RATIONALE: Population and health services research can be performed by linkage
      analysis of administrative data. However, the robustness of study results is
      determined by the accuracy of the diagnostic coding. OBJECTIVES: To estimate the
      awareness, use and accuracy of the International Classification of Diseases,
      Ninth Revision (ICD-9) coding by physicians providing services for patients with
      Crohn's disease (CD) and ulcerative colitis (UC). METHODS: All Ontario
      gastroenterologists and a 10% random sample of internists, pediatricians,
      pediatric or general surgeons, and family physicians were surveyed by postal
      questionnaire to estimate the frequency and 95% CI of using codes 555 or 556 when
      billing for CD- and UC-related services, respectively. c2 tests were used for
      between-group comparisons. RESULTS: Of the physicians who were surveyed, 67.7%
      (416 of 614) responded; 258 of 391 (66%) who were still practising in Ontario saw
      patients with inflammatory bowel disease (IBD), and 54% had more than 10 IBD
      patients; 86.5% (95% CI 82.4% to 90.6%) were familiar with ICD-9 codes, and 91.4%
      (95% CI 88.1% to 95.6%) used the codes 555 (CD) or 556 (UC) for billing. Rates of
      ICD-9 use did not differ by sex but were used more frequently by those graduating
      after 1981 (P<0.02). Gastroenterologists used ICD-9 IBD codes 555 or 556
      significantly more often than all other physicians (P=0.001). Most (more than
      75%) Ontario physicians used ICD-9 IBD codes always or frequently when billing
      for IBD-related services. Few (10%) used these codes to bill for non-IBD-related
      problems. CONCLUSIONS: These data suggest that there is acceptable use and
      accuracy of ICD-9 diagnostic coding for CD and UC services - comparable with
      results from studies of other diseases. Administrative data may thus be used to
      undertake epidemiological studies in IBD in Ontario.

PMID- 12226680
TI  - Helicobacter pylori anti-CagA antibodies: prevalence in symptomatic and
      asymptomatic subjects in Turkey.
AB  - BACKGROUND: Several reports have shown the prevalence of anti-CagA antibodies to
      be associated with the development of peptic ulcer diseases, while others have
      indicated that there is no such association. AIM: To examine the prevalence of
      antibodies to CagA and other Helicobacter pylori antigens in symptomatic and
      asymptomatic subjects in Turkey. subjects and METHODS: Sixty-six symptomatic
      subjects, 16 to 74 years of age, were examined for H pylori by biopsy-based tests
      and ELISA. One hundred nineteen asymptomatic subjects, 20 to 65 years of age,
      were also tested serologically for the presence of H pylori. Samples from both
      groups that were found to be positive for H pylori by ELISA were then tested by
      immunoblotting. RESULTS: Fifty-four (82%) symptomatic subjects and 76 (64%)
      asymptomatic subjects were found to be H pylori-positive by ELISA. Samples from
      30 symptomatic subjects who were found to be H pylori-positive by ELISA were
      analyzed by immunoblotting. Antibodies to CagA (116 kDa) antigen were detected in
      immunoblots of 11 of 14 (79%) with chronic gastritis, 12 of 13 (92%) with
      duodenal ulcer and three of three (100%) with gastric cancer. Antigens of the
      following molecular weights were also detected in these 30 subjects: 89 kDa
      (VacA) in 21 (70%), 37 kDa in 21 (70%), 35 kDa in 19 (63%), 30 kDa in 27 (90%)
      and 19.5 kDa in 19 (63%). Immunoblots of 40 ELISA-positive asymptomatic subjects
      showed that 33 (83%) had antibodies to CagA antigen, 26 (65%) to VacA antigen, 30
      (75%) to a 37 kDa antigen, 30 (75%) to a 35 kDa antigen, 39 (98%) to a 30 kDa
      antigen and 36 (90%) to a 19.5 kDa antigen. CONCLUSIONS: Antibodies to CagA
      antigen were prevalent in both groups, regardless of the presence of
      gastroduodenal disease.

PMID- 12226681
TI  - The tyranny of the scope.

PMID- 12226682
TI  - Motion - Screening and surveillance of Barrett's epithelium is practical and cost
      effective: arguments against the motion.
AB  - The issue of whether to screen individuals for Barrett's esophagus (BE) to
      prevent esophageal adenocarcinoma (EAC) is highly controversial. Important
      considerations are that BE is not highly prevalent in the general population and
      that not many patients with BE develop or die from EAC. Studies that suggest an
      improved prognosis from surveillance programs are susceptible to lead-time bias.
      Most of the principles for effective screening, as outlined by the World Health
      Organization, are not met by endoscopic screening and surveillance protocols. The
      diagnosis of BE (and dysplasia) is often unclear. Most patients with BE are not
      identified by screening, and few deaths would be prevented by surveillance. A
      decision analysis found that the most cost effective screening protocol would be
      every five years, but the costs associated with prolongation of life are very
      high, even if a group at high risk for EAC could be identified.

PMID- 12226683
TI  - Motion - All patients with GERD should be offered once in a lifetime endoscopy:
      arguments for the motion.
AB  - Proton pump inhibitor therapy is so successful at relieving reflux-related
      symptoms and healing esophageal erosions that it has supplanted formal diagnostic
      techniques, such as endoscopy and esophageal pH monitoring, for the initial
      management of gastroesophageal reflux disease. The response to antisecretory
      therapy is not indicative, however, of Barrett's esophagus or esophageal
      adenocarcinoma. Patients with prolonged and severe reflux symptoms, especially if
      they are over the age of 60 years, are at risk of these complications. For them,
      endoscopy is the only appropriate investigation for detecting Barrett's esophagus
      and dysplasia or cancer. Because of the difficulty in distinguishing dysplasia
      from inflammatory and regenerative changes, endoscopy should be undertaken while
      the patient is on effective antisecretory therapy. Endoscopy should be offered
      only to patients who are suitable for further therapy (especially esophagectomy),
      and only if they understand the implications of abnormal findings. The published
      evidence suggests that the application of clear guidelines would not overwhelm
      health care resources, and that fewer than 20% of patients with Barrett's
      esophagus would eventually undergo endoscopic surveillance.

PMID- 12226684
TI  - Motion - All patients with GERD should be offered once in a lifetime endoscopy:
      arguments against the motion.
AB  - The evidence for the recommendation that patients with gastroesophageal reflux
      disease (GERD) be offered once in a lifetime endoscopy is weak and is not
      supported by any clinical trials. GERD is a very prevalent condition, yet only
      10% of patients with GERD have Barrett's esophagus (BE). Esophageal
      adenocarcinoma (EAC) is a rare condition and is uncommon even among patients with
      BE. A decision analysis found that surveillance of BE patients is performed
      because of inflated estimates of the rate of progression from BE to EAC.
      Dysplasia more often regresses to more benign histological findings than to
      cancer, and transient dysplasia can also lead to a high rate of unnecessary
      endoscopy. Even though practice guidelines about endoscopic surveillance have
      been published, there is no consensus among gastroenterologists about appropriate
      protocols, and many physicians are more aggressive than the guidelines. It has
      not been proved that surveillance saves lives, in part because BE rarely leads to
      death from EAC. The favourable results from some specialized centres may not be
      widely applicable. The recommendation for 'once in a lifetime' endoscopy for GERD
      patients is premature.

PMID- 12226685
TI  - Two decades of Helicobacter pylori: a review of the Fourth Western Pacific
      Helicobacter Congress.
AB  - From March 3 to 6, 2002, Helicobacter enthusiasts gathered in Perth, Australia
      for the Fourth Western Pacific Helicobacter Congress to celebrate the 20th
      anniversary of the modern discovery of this organism by Barry Marshall and Robin
      Warren. The meeting included state-of-the-art lectures highlighting the
      breakthroughs that have occurred since the discovery of this bacterium. As well,
      advances from the forefront of current Helicobacter pylori research were
      presented, particularly in the realm of genomics and molecular biology. A
      symposium about vaccines and trends for future H pylori research completed this
      congress. The purpose of the present review is to summarize the highlights from
      this conference, emphasizing new advances.

PMID- 12226686
TI  - The CAG Research Committee report: investment in excellence.

PMID- 12226688
TI  - Cost analysis in a clinical microbiology laboratory.
AB  - The use of models for business management and cost control in public hospitals
      has led to a need for microbiology laboratories to know the real cost of the
      different products they offer. For this reason, a catalogue of microbiological
      products was prepared, and the costs (direct and indirect) for each product were
      analysed, along with estimated profitability. All tests performed in the
      microbiology laboratory of the "Virgen de la Concha" Hospital in Zamora over a 2
      year period (73192 tests) were studied. The microbiological product catalogue was
      designed using homogeneity criteria with respect to procedures used, workloads
      and costs. For each product, the direct personnel costs (estimated from workloads
      following the method of the College of American Pathologists, 1992 version), the
      indirect personnel costs, the direct and indirect material costs and the portion
      of costs corresponding to the remaining laboratory costs (capital and structural
      costs) were calculated. The average product cost was 16.05 euros. The average
      cost of a urine culture (considered, for purposes of this study, as a relative
      value unit) reached 13.59 euros, with a significant difference observed between
      positive and negative cultures (negative urine culture, 10.72 euros; positive
      culture, 29.65 euros). Significant heterogeneity exists, both in the costs of
      different products and especially in the cost per positive test. The application
      of a detailed methodology of cost analysis facilitates the calculation of the
      real cost of microbiological products. This information provides a basic tool for
      establishing clinical management strategies.

PMID- 12226687
TI  - Impact of previous use of antibiotics on development of resistance to extended
      spectrum cephalosporins in patients with enterobacter bacteremia.
AB  - This retrospective study was conducted to determine the risk factors for
      resistance to extended-spectrum cephalosporins (ESCs) and to examine the
      influence of previous use of an aminoglycoside with an ESC on resistance to ESCs
      in patients with Enterobacter bacteremia from January 1991 through December 2000.
      A total of 423 episodes of Enterobacter bacteremia among 414 patients were
      documented during the 10-year study period. Three hundred thirty-two (78%)
      isolates were Enterobacter cloacae, 72 (17%) Enterobacter aerogenes, and 19 (4%)
      other Enterobacter species. Causative isolates exhibited resistance to ESCs in
      225 episodes and susceptibility in 198 episodes. Nosocomial acquisition was an
      independent risk factor for resistance to ESCs (odds ratio [OR], 3.4; 95%
      confidence interval [95%CI], 1.7-6.8). The median number of antibiotics used was
      significantly greater in cases caused by resistant isolates than in cases caused
      by susceptible isolates (OR, 1.8; 95%CI, 1.2-2.6). Resistance to ESCs was
      associated with previous use of any ESC (OR, 5.0; 95%CI, 2.5-10.2). The
      proportion of resistant episodes in patients treated previously with an
      aminoglycoside plus an ESC was not different from that in patients treated with
      an ESC alone. In conclusion, previous use of ESCs was associated with resistance
      to ESCs in patients with Enterobacter bacteremia; moreover, previous use of an
      aminoglycoside with an ESC did not significantly decrease the risk of resistance
      to ESCs.

PMID- 12226689
TI  - Clonal relationships among isolates of erythromycin-resistant Streptococcus
      pyogenes of different geographical origin.
AB  - The clonal relationships among 261 erythromycin-resistant Streptococcus pyogenes
      isolates collected in 1986-1997 from nine countries in Europe and North and South
      America were studied by using two molecular typing methods: Vir typing and random
      amplified polymorphic DNA (RAPD) analysis. A total of 49 different Vir genotypes
      (VTs) and 33 different RAPD patterns were noted among the 261 isolates. Isolates
      that shared the same VT and RAPD pattern were considered to belong to the same
      clone. Although as many as 60 different clones were found among the isolates
      studied, only seven clones, comprising 157 of the 261 (60%) isolates, were found
      in more than one country. Five of these seven clones expressed the M phenotype
      known to be associated with the drug efflux mechanism, and only two clones
      expressed the macrolide-lincosamide-streptogramin B-resistance phenotype. The
      results indicate a polyclonal spread of erythromycin-resistant Streptococcus
      pyogenes. Furthermore, predominance of the seven clones indicates that
      erythromycin-resistant Streptococcus pyogenes of the same clonal origin may be
      widely distributed and found in several different countries.

PMID- 12226690
TI  - Nosocomial outbreak of multidrug-resistant tuberculosis caused by a strain of
      Mycobacterium tuberculosis W-Beijing family in St. Petersburg, Russia.
AB  - A molecular epidemiologic study of 35 Mycobacterium tuberculosis isolates from 19
      patients was conducted to define a nosocomial outbreak of multidrug-resistant
      tuberculosis in St. Petersburg, Russia. IS 6110-restriction fragment length
      polymorphism (RFLP) fingerprinting, together with investigations to detect
      mutations conferring drug resistance, revealed relationships between the isolates
      and links between the cases. Three patients and a nurse exposed to active
      tuberculosis were proved to be involved in the outbreak; the source case was
      identified. The outbreak strain possessed a 17-band RFLP pattern and a
      spoligoprofile (signals 35-43) characteristic of the W-Beijing family as well as
      distinctive mutations in katG315, rpoB531, embB306 and rpsL43. This specific RFLP
      pattern has previously been identified among Mycobacterium tuberculosis W-Beijing
      strains isolated across the former Soviet Union and in the St. Petersburg area of
      Russia. The spread of multidrug-resistant strains of W-Beijing genotype in the
      general population and in hospital settings presents a serious threat for public
      health in Russia. Specific pathogenic properties of W-Beijing genotype strains,
      such as enhanced transmissibility and the ability to cause reinfection and to
      readily acquire drug resistance to major antituberculosis drugs, along with
      special features of host response, have yet to be investigated.

PMID- 12226691
TI  - Crimean-Congo hemorrhagic fever in Albania, 2001.
AB  - During the spring and summer of 2001, an outbreak of eight cases of Crimean-Congo
      hemorrhagic fever (CCHF) occurred in Albania. The epidemiological investigation,
      the clinical presentation of the cases, and the course of the disease are
      described. Seven of the cases were laboratory confirmed. A nosocomial infection
      and a cluster of cases within a family were observed. Genetic analysis of the
      CCHF virus strain that caused the outbreak showed that it was clustered together
      with other European CCHF virus strains except the Greek one (strain AP92). The
      Greek strain, which forms an independent clade, differed from the causative
      strain by 25.3% at the nucleotide level.

PMID- 12226692
TI  - Emerging role of Mycoplasma pneumoniae in children with acute pharyngitis.
AB  - In order to define the role, the risk factors, and the clinical and laboratory
      characteristics of Mycoplasma pneumoniae infection in children with pharyngitis,
      184 patients with acute non-streptococcal pharyngitis (102 males; median age,
      5.33 years) were studied. Acute Mycoplasma pneumoniae infection was demonstrated
      in 44 (23.9%) patients. A history of recurrent episodes of pharyngitis (defined
      as at least 3 acute episodes of pharyngitis in the 6 months preceding enrollment)
      appeared to be the more useful parameter for differentiating Mycoplasma
      pneumoniae pharyngitis from non-streptococcal non- Mycoplasma pneumoniae
      pharyngitis ( P<0.05 in multivariate analysis). These data, which highlight the
      emerging role of Mycoplasma pneumoniae in acute pharyngitis, must be taken into
      account in the diagnosis and treatment of this clinical manifestation in
      children.

PMID- 12226693
TI  - Rare presentation of Streptococcus pneumoniae pneumonia with bacteremia and
      multiple subcutaneous abscesses.
AB  - Reported here is the case of an apparently immunocompetent patient with
      Streptococcus pneumoniae pneumonia and bacteremia who presented with abscesses in
      multiple soft tissue sites. This unusual presentation provided a purulent
      aspirate for presumptive etiologic diagnosis by a Gram-stained smear.

PMID- 12226694
TI  - Cluster of neonatal infections in Jerusalem due to unusual biochemical variant of
      Enterobacter sakazakii.
AB  - Reported here is a cluster of infections due to a nitrate-negative variant of
      Enterobacter sakazakii, which occurred among premature neonates at the Hadassah
      Hospital, Mount Scopus, Jerusalem, in December 1999-January 2000. Pulsed-field
      gel electrophoresis showed cluster isolates to be identical but unrelated to
      previous systemic isolates recovered in 1993 and 1998. The organism was not
      isolated from infant formula powder, but it was recovered from prepared formula
      and from a kitchen blender. Elimination of the environmental focus, a change to
      factory-prepared infant formula, and isolation of affected infants terminated the
      event. Faecal carriage of Enterobacter sakazakii was observed for up to 18 weeks,
      emphasising the potential for cross-infection.

PMID- 12226695
TI  - Two cases of imported gnathostomiasis in Spanish women.
AB  - Reported here are two new cases of imported cutaneous gnathostomiasis that
      occurred in two Spanish women. The first patient acquired the helminth infection
      while travelling in Southeast Asia and the second in Mexico. Although the highest
      prevalence of gnathostomiasis infection is in Southeast Asia, the disease is now
      an emerging public health problem in some countries of Latin America. The cases
      reported here demonstrate the increasing frequency with which human
      gnathostomiasis is being diagnosed in nonendemic countries as a result of more
      extensive international travel and migration.

PMID- 12226696
TI  - Selection of oxacillin resistance in oxacillin-sensitive Staphylococcus aureus
      through exposure to ciprofloxacin but not piperacillin/tazobactam.
AB  - Ten oxacillin-sensitive Staphylococcus aureus strains were grown on agar
      containing four times their ciprofloxacin MIC to determine if exposure to
      ciprofloxacin would increase their resistance to oxacillin. All strains grew on
      the ciprofloxacin-containing agar and subsequently grew on oxacillin-salt agar.
      The geometric mean MICs for oxacillin increased one- to sixteen-fold and remained
      elevated after ten passages on antibiotic-free agar. The mecA gene was not
      detected in any strain. There was no increase in oxacillin MICs when the bacteria
      were passaged on agar containing four times their MIC of piperacillin/tazobactam.
      Exposure of oxacillin-sensitive strains of Staphylococcus aureus to ciprofloxacin
      may increase their MICs to oxacillin.

PMID- 12226697
TI  - Evaluation of an immunochromatographic dip-strip test for the detection of
      Cryptosporidium oocysts in stool specimens.
AB  - The study presented here examined the efficacy of a commercially available
      qualitative immunochromatographic assay for detecting Cryptosporidium oocysts in
      stool samples. A total of 75 samples were tested, including 50 positive for
      Cryptosporidium spp. by acid-fast stain, 20 positive for other parasites (
      Blastocystis hominis, Endolimax nana, Entamoeba coli, Giardia lamblia, Ascaris
      lumbricoides, Strongyloides stercoralis and Trichuris trichiura), and five
      negative samples. The observed sensitivity was 98%, while specificity was 100%;
      the detection threshold was near 1000 oocysts/ml. Correctly diagnosed positive
      samples included Cryptosporidium parvum genotypes 1 and 2, whereas the single
      false-negative sample corresponded to a Cryptosporidium meleagridis infection.

PMID- 12226698
TI  - Hantavirus infections in Latvia.
AB  - In order to investigate the presence of hantavirus infections in Latvia, 333
      randomly selected human serum samples were screened using an enzyme-linked
      immunoassay. Fifteen samples were positive for hantavirus-specific IgG and were
      subsequently serotyped using a focus reduction neutralization test. Fourteen of
      these samples neutralized at least one of the hantaviruses included in the test,
      indicating a 4.2% overall seroprevalence in Latvia. Among 14 focus reduction
      neutralization test-positive sera, specific reactivity (at least 4-fold higher
      endpoint titer) of neutralizing antibodies was as follows: six sera were specific
      for Saaremaa hantavirus, three showed equal titers to Saaremaa and Dobrava
      hantaviruses, and five showed the highest endpoint titers to Puumala hantavirus.
      Hantavirus infections were confirmed in individuals residing in 11 of 26
      investigated counties. The sex ratio was 1:2.5 (M:F), and the antibody prevalence
      increased with age. This is the first report on the presence of hantavirus
      infections in Latvia, and the results indicate that two hantaviruses pathogenic
      to man, Saaremaa virus and Puumala virus, are widely distributed in this country.

PMID- 12226699
TI  - First report of urinary tract infection due to Pichia ohmeri.

PMID- 12226700
TI  - Combined antifungal treatment of visceral mucormycosis with caspofungin and
      liposomal amphotericin B.

PMID- 12226701
TI  - Candida dubliniensis bloodstream infection in patients with gynaecological
      malignancy.

PMID- 12226702
TI  - A case of Cryptosporidiosis in pregnancy.

PMID- 12226703
TI  - Extended pathogenicity of recombinant polioviruses.

PMID- 12226704
TI  - Emerging links between initiation of translation and human diseases.
AB  - Some diseases are caused by mutations that perturb the initiation step of
      translation by changing the context around the AUG(START) codon or introducing
      upstream AUG codons. The scanning mechanism provides a framework for
      understanding the effects of these and other structural changes in mRNAs derived
      from oncogenes, tumor suppressor genes, and other key regulatory genes. In mRNAs
      from mutated as well as normal genes, translation sometimes initiates from an
      internal AUG codon. Sanctioned mechanisms that allow this, including leaky
      scanning and reinitiation, are discussed. Thrombopoietin mRNA is an example in
      which translation normally initiates from an internal position via an inefficient
      reinitiation mechanism. Mutations that restructure this mRNA in ways that elevate
      production of thrombopoietin cause hereditary thrombocythemia, demonstrating that
      some mRNAs are designed deliberately with upstream AUG codons to preclude
      efficient translation and thus to prevent harmful overproduction of potent
      proteins. While upstream AUG codons in certain mRNAs thus play an important
      regulatory role, the frequency of upstream AUG codons tends to be exaggerated
      when cDNA sequences are compiled and analyzed. Because the discovery of mutations
      that perturb translation usually begins with cDNA analysis, some
      misunderstandings vis-a-vis the interpretation of cDNA sequences are discussed.

PMID- 12226705
TI  - QTL analyses of spontaneous activity by using mouse strains from Mishima battery.
AB  - We reported previously that spontaneous activity in the home cage is highly
      variable among the Mishima battery of mouse strains. In that study, NJL and KJR
      were found to be hyperactive strains in contrast to BLG2, which showed one of the
      lowest activity levels. To unravel the genetic loci involved in this behavioral
      phenotype, we conducted QTL analyses on backcross populations of crosses between
      either NJL or KJR and BLG2 strains. In the backcross of NJL to BLG2, no single
      locus was associated with increased spontaneous activity. In the backcross of KJR
      to BLG2, linkage analysis showed that a locus on the most telomeric region of
      Chromosome (Chr) 3 was involved in the spontaneous activity, thus named Loco1.
      Further linkage analysis using selected progeny carrying the allele from KJR at
      the Loco1 locus suggested the presence of another locus, Loco2, on Chr 17. An
      analysis showed that Loco1 and Loco2 interacted epistatically.

PMID- 12226706
TI  - A chromosomal translocation causing multiple abnormalities including open eyelids
      at birth and glomerulonephritis.
AB  - We have characterized the phenotype of a mouse with a t(2;13) reciprocal
      translocation induced by chlorambucil. It results in abnormal eyelid formation as
      well as a series of neurological, physiological, and immunological abnormalities.
      This mutant has been termed T(2;13)1Fla/+. T(2;13)1Fla/+ mice exhibit open
      eyelids at birth, a dilute coat color, hyperactivity, and occasional circling and
      stargazing activity. At 1-6 months, T(2;13)1Fla/+ mice show signs of immune
      complex-mediated glomerulonephritis and die prematurely. Additionally, double
      stranded DNA autoantibodies have been found in sera of T(2;13)1Fla/+ mice.
      Cytogenetic analysis situated the translocation breakpoint at the proximal end of
      Chromosome (chr) 2 at band A2, and on Chr 13 at band A4. The mutant phenotype
      completely correlated with the presence of the translocation. Additional genetic
      studies have mapped the mutation and translocation breakpoint to Chr 13 between
      D13Mit16 and D13Mit64, and to Chr 2 proximal to D2Mit5. By fluorescent in situ
      hybridization (FISH), the position of this mutation/translocation on Chr 13 has
      been mapped to a region less than 1cM from D13Mit61.

PMID- 12226707
TI  - Insertional polymorphisms of ETn retrotransposons include a disruption of the wiz
      gene in C57BL/6 mice.
AB  - ETn (early transposon) elements are moderate repetitive sequences present in
      hundreds of copies in the mouse genome. Their length ranges from 4.4 to 7.1 kb,
      and, like transposons, they contain long terminal repeats (LTRs) on both sides
      and are flanked by target site duplications (Kaghad et al. 1985). ETn-related
      elements can be grouped into three distinct families. Members of the ETn I and
      ETn II families mainly contain sequences of unknown origin in their core region.
      Only very short stretches of retrovirus-like sequences are present, and there are
      no ORFs. ETn I and ETn II elements differ primarily in the 3- half of both the 5-
      and 3- LTR, and in the 5- end of the core region (see Fig. 1). As a consequence,
      only ETn II elements contain a primer binding site for tRNALys. In contrast to
      ETn I and ETn II, members of the recently described MusD family (Mager and
      Freeman 2000) contain ORFs for (at least parts of) D-type virus Gag, Pro, and Pol
      proteins. However, in other regions they are structurally similar to ETn II
      elements and contain an intact primer binding site. It has been shown that MusD
      sequences are evolutionarily older than ETn II elements, suggesting that the
      latter might have arisen by recombinatory replacement of the MusD gene-coding
      sequences with sequences of unknown origin (Mager and Freeman 2000). ETn elements
      are still active as retrotransposons. In the past years, several germ line and
      somatic mutations caused by fresh ETn integrations have been found (Table 1).
      From 19 mutations, sufficient sequence is available in seven cases to show that
      the insertion was an ETn II element. In eight cases, the sequence data available
      indicate either an ETn II or a MusD element. ETn I has not been found to be the
      cause of any mutations, prompting the suggestion that ETn II is the "mobile"
      family, whereas ETn I elements have lost the capacity to retrotranspose.

PMID- 12226708
TI  - Inbred strain variation in lung function.
AB  - The purpose of the present study was to determine the strain-specific phenotype
      variance of lung function parameters among common inbred laboratory mouse
      strains. In accordance with the "Mouse Phenome Project" run by The Jackson
      Laboratory (http://www.jax.org/phenome), lung volumes, lung mechanics, and
      diffusing capacity of 16 males and 16 females of the strains C3H/HeJ, BALB/cByJ,
      C57B1/6J, A/J, FVB/J, 129SV/ImJ, and SWR/J were determined in a standardized
      manner. The defined respiratory maneuvers for lung function testing were
      performed with a custom-made, computer-controlled servo-ventilator in
      anesthetized animals. Sex differences within the strains were found in most (83%)
      of the absolute lung function parameters. Usually, normalization to body or lung
      size completely compensates for the observed gender differences. There was great
      diversity between strains for all of the lung function parameters studied; for
      example, the total lung capacity as well as the pulmonary diffusing capacity for
      carbon monoxide varied by 50% and the static lung compliance by a factor of
      almost two among the strains. Little, but statistically significant variability
      was detectable for the dead space volume and the respiratory system resistance.
      There was no clear-cut evidence for any strain exhibiting either the smallest or
      the largest values for all parameters studied, suggesting that there were no
      simple allometric relationships of lung size between the strains. Well
      established genealogical relationships among strains were not constantly
      reflected in phenotype similarities of pulmonary function. Therefore, these data
      strongly support heritable genetic traits for pulmonary function. Moreover, it
      constitutes a basis for further genetic lung function-related studies.

PMID- 12226709
TI  - Pattern of segmental recombination in the distal inversion of mouse t haplotypes.
AB  - To examine genetic exchange between t haplotypes and their wild-type homologs,
      four previously identified mouse Chromosome (Chr) 17 variants termed mosaic
      haplotypes were analyzed in detail. Three of these haplotypes-one from a Mus
      musculus population in Bulgaria, one from a Mus domesticus population in Chile,
      and one from a M. domesticus population in Germany-display properties indicative
      of the t complex. All four haplotypes are exceptional because they are
      characterized by the presence of a few wild-type DNA markers in the distal
      inversion [In(17)4] of a t haplotype chromosome: thus, they are classified as
      mosaic t haplotypes. The mosaic pattern for each haplotype is distinct, however.
      We compared the mosaic haplotypes with each other, and with several well
      characterized laboratory t haplotypes, by analyzing several DNA markers in the
      In(17)4 region of the t complex, where all of the mosaicism occurs. We used a
      combination of high-resolution restriction mapping, DNA sequencing, and analysis
      of new DNA markers to classify the haplotypes. This analysis shows that segmental
      exchange, either by gene conversion or double crossing-over, has occurred at
      molecular markers in the vicinity of a gene, Dnahc8, that is a candidate for the
      t complex distorter locus Tcd2. While it is unclear whether segmental exchanges
      have included the Tcd2 gene, it is apparent that several independent
      recombination events have occurred in In(17)4 during the recent evolution of t
      haplotypes.

PMID- 12226710
TI  - Identification and characterization of a novel murine beta-defensin-related gene.
AB  - Beta-defensins comprise a family of cationic peptides, which are predominately
      expressed at epithelial surfaces and have a broad-range antimicrobial activity.
      We have assembled two BAC-based contigs from the chromosomal region 8A4 that
      contain the murine defensins, and we have mapped six reported beta-defensin
      genes. In addition, we have isolated and functionally characterized a novel beta
      defensin gene that deviates from the canonical six cysteine motif present in the
      mature functional peptide of all other beta-defensins. This defensin-related gene
      (Defr1) is most highly expressed in testis and heart. The genomic organization is
      highly similar to Defb3, 4, 5, and 6, and the exon 1 sequence is very highly
      conserved. A synthetic Defr1 peptide displayed antimicrobial activity against
      Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Burkholderia
      cepacia. The antimicrobial activity of Defr1 against S. aureus, E.coli, and B.
      cepacia was found to be reduced in raised concentration of NaCl, but its action
      against P. aeruginosa was independent of NaCl concentration. This is the first
      report of a functional beta defensin that lacks one of the conserved cysteine
      residues in its predicted mature peptide. This study has major implications for
      the structure and functions of these important host defense molecules.

PMID- 12226711
TI  - V76D mutation in a conserved gD-crystallin region leads to dominant cataracts in
      mice.
AB  - During a large-scale ENU mutagenesis screen, a mouse mutant with a dominant
      cataract was detected and referred to as Aey4. Aim of this study was the
      morphological description of the mutant, the mapping of the mutation, and the
      characterization of the underlying molecular lesion. The slit-lamp examination
      revealed a strong nuclear cataract surrounded by a homogeneous milky opacity in
      the inner cortex. The histological analysis demonstrated remnants of cell nuclei
      throughout the entire lens. The mutation was mapped to Chromosome 1 by a genome
      wide linkage making the six gamma-crystallin encoding genes and the closely
      linked betaA2-crystallin encoding gene to relevant candidate genes. Finally, a T-
      >A exchange in exon 2 of the gammaD-crystallin encoding gene (symbol: Crygd) was
      demonstrated to be causative for the cataract phenotype; this particular mutation
      is, therefore, referred to Crygo(Aey4). The alteration in codon 76 leads to an
      amino acid exchange of Val-->Asp. Val at this position is highly conserved; it is
      found in all mouse and rat gammaD/E/F-crystallins as well as in the human gammaA-
      and gammaD-crystallins. It may be replaced solely by Ile, which is present in all
      bovine gamma-crystallins, in the rat and mouse gammaA/B/C-crystallins, as well as
      in the human gammaB/C-crystallins. It is predicted that the exchange of a
      hydrophobic side chain by a polar and acidic one might influence the
      microenvironment by a dramatic decrease of the isoelectric point by 1.5 pH units
      in the 10 amino acids surrounding position 76. The Crygd(Aey4) additionally
      demonstrates the importance of the integrity of the Cryg gene cluster for lens
      transparency.

PMID- 12226712
TI  - Segmental paralogy in the human genome: a large-scale triplication on 1p, 6p, and
      21q.
AB  - Few cases of large-scale segmental paralogy have been reported in the human
      genome. We have identified a large (approximately 500 kb) segment on human
      chromosome (HC) 21 (21q22) that is triplicated on HC 1 (1p35) and HC 6 (6p12-21).
      We also identified a new member of CLIC (Chloride Intracellular Channel) family
      on 21q, namely CLIC6. All three segments appear to include three functional
      members of three different gene families: DSCR1-like (Down Syndrome Candidate
      Region 1-like), CLIC, and AML/Runt (Acute Myeloid Leukemia/Runt). Molecular
      evolution analysis shows a common evolutionary origin for the triplicated
      regions. This finding of a further large-scale genomic triplication that went
      undetected at previously systematic automated searches provides a new model for
      gene divergence study and underlines the need for new tools to effectively detect
      inter-chromosomal similarity. An algorithm to overcome current limitations is
      proposed.

PMID- 12226713
TI  - The human-specific Yp11.2/Xq21.3 homology block encodes a potentially functional
      testis-specific TGIF-like retroposon.
AB  - Yp11.2/Xq21.3 is a human-specific homology block that constitutes the largest
      shared region among the sex chromosomes, spanning some 3.5 Mb. Only two
      transcribed sequences have been mapped to this segment: the protocadherin genes
      PCDHX/Y, and the X-linked poly(A)-binding protein PABPC5 gene, whose Y-homolog
      has been lost during human evolution. This paper reports the genomic structure,
      expression, and evolutionary conservation of a third (X-Y homologous) transcribed
      sequence, TGIFLX/Y (TGIF-like X/Y), mapping to this region. TGIFLX/Y has a 2666
      bp mRNA encoded by two exons separated by a 96-bp intron. TGIFLX/Y are
      homeodomain-containing genes related to the TALE superclass gene family.
      Comparative DNA analysis indicates that TGIFLX originated from retrotransposition
      of TGIF2, located on 20q11.2-12, onto the X Chromosome. RT-PCR analysis reveals
      that both X- and Y-linked genes are specifically expressed in adult testis.
      Cloning and sequencing of TGIFLX homologs in hominoids and Old World monkeys
      provides evidence for an open reading frame in the eight species studied.
      Interestingly, a single base pair deletion in the human TGIFLY (as compared with
      TGIFLX) creates a different reading frame where the C-terminal residues shared by
      TGIFLX and other TGIF proteins are missing. The conservation, similarity to
      protein-encoding transcription factors, and specific expression in testis points
      to a transcriptional role for TGIFLX/Y in this tissue.

PMID- 12226714
TI  - A bovine whole-genome radiation hybrid panel and outline map.
AB  - A 3000-rad radiation hybrid panel was constructed for cattle and used to build
      outline RH maps for all 29 autosomes and the X and Y chromosomes. These outline
      maps contain about 1200 markers, most of which are anonymous microsatellite loci.
      Comparisons between the RH chromosome maps, other published RH maps, and linkage
      maps allow regions of chromosomes that are poorly mapped or that have sparse
      marker coverage to be identified. In some cases, mapping ambiguities can be
      resolved. The RH maps presented here are the starting point for mapping
      additional loci, in particular genes and ESTs that will allow detailed
      comparative maps between cattle and other species to be constructed. Radiation
      hybrid cell panels allow high-density genetic maps to be constructed, with the
      advantage over linkage mapping that markers do not need to be polymorphic. A
      large quantity of DNA has been prepared from the cells forming the RH panel
      reported here and is publicly available for mapping large numbers of loci.

PMID- 12226715
TI  - Porcine gene discovery by normalized cDNA-library sequencing and EST cluster
      assembly.
AB  - Genetic and environmental factors affect the efficiency of pork production by
      influencing gene expression during porcine reproduction, tissue development, and
      growth. The identification and functional analysis of gene products important to
      these processes would be greatly enhanced by the development of a database of
      expressed porcine gene sequence. Two normalized porcine cDNA libraries (MARC 1PIG
      and MARC 2PIG), derived respectively from embryonic and reproductive tissues,
      were constructed, sequenced, and analyzed. A total of 66,245 clones from these
      two libraries were 5?-end sequenced and deposited in GenBank. Cluster analysis
      revealed that within-library redundancy is low, and comparison of all porcine
      ESTs with the human database suggests that the sequences from these two libraries
      represent portions of a significant number of independent pig genes. A Porcine
      Gene Index (PGI), comprising 15,616 tentative consensus sequences and 31,466
      singletons, includes all sequences in public repositories and has been developed
      to facilitate further comparative map development and characterization of porcine
      genes (http://www.tigr.org/tdb/ssgi/). The clones and sequences from these
      libraries provide a catalog of expressed porcine genes and a resource for
      development of high-density hybridization arrays for transcriptional profiling of
      porcine tissues. In addition, comparison of porcine ESTs with sequences from
      other species serves as a valuable resource for comparative map development. Both
      arrayed cDNA libraries are available for unrestricted public use.

PMID- 12226716
TI  - Enzymatic production of cyclodextrins.
AB  - Cyclodextrins (CD) are enzymatically modified starches with a wide range of
      applications in food, pharmaceutical and chemical industries, agriculture and
      environmental engineering. They are produced from starch via enzymatic conversion
      using cyclodextrin glycosyl transferases (CGTases) and partly alpha-amylases. Due
      to its low solubility in water, separation and purification of beta-CD is
      relatively easy compared to alpha- and gamma-CD. In recent years more economic
      processes for gamma-CD and especially alpha-CD production have been developed
      using improved CGTases and downstream processing. New purification steps, e.g.
      affinity adsorption, may reduce the use of complexing agents. The implementation
      of thermostable CGTases can simplify the production process and increase the
      selectivity of the reaction. A tabular overview of alpha-CD production processes
      is presented.

PMID- 12226717
TI  - A review of the production of ethanol from softwood.
AB  - Ethanol produced from various lignocellulosic materials such as wood,
      agricultural and forest residues has the potential to be a valuable substitute
      for, or complement to, gasoline. One of the major resources in the Northern
      hemisphere is softwood. This paper reviews the current status of the technology
      for ethanol production from softwood, with focus on hemicellulose and cellulose
      hydrolysis, which is the major problem in the overall process. Other issues of
      importance, e.g. overall process configurations and process economics are also
      considered.

PMID- 12226718
TI  - Biofouling in water systems--cases, causes and countermeasures.
AB  - Biofouling is referred to as the unwanted deposition and growth of biofilms. This
      phenomenon can occur in an extremely wide range of situations, from the
      colonisation of medical devices to the production of ultra-pure, drinking and
      process water and the fouling of ship hulls, pipelines and reservoirs. Although
      biofouling occurs in such different areas, it has a common cause, which is the
      biofilm. Biofilms are the most successful form of life on Earth and tolerate high
      amounts of biocides. For a sustainable anti-fouling strategy, an integrated
      approach is suggested which includes the analysis of the fouling situation, a
      selection of suitable components from the anti-fouling menu and an effective and
      representative monitoring of biofilm development.

PMID- 12226719
TI  - An improved stereoselective reduction of a bicyclic diketone by Saccharomyces
      cerevisiae combining process optimization and strain engineering.
AB  - The stereoselective reduction of the bicyclic diketone bicyclo[2.2.2]octane-2,6
      dione, to the ketoalcohol (1R,4S,6S)-6-hydroxybicyclo[2.2.2]octane-2-one, was
      used as a model reduction to optimize parameters involved in NADPH-dependent
      reductions in Saccharomyces cerevisiae with glucose as co-substrate. The co
      substrate yield (ketoalcohol formed/glucose consumed) was affected by the initial
      concentration of bicyclic diketone, the ratio of yeast to glucose, the medium
      composition, and the pH. The reduction of 5 g l(-1) bicyclic diketone was
      completed in less than 20 h in complex medium (pH 5.5) under oxygen limitation
      with an initial concentration of 200 g l(-1) glucose and 5 g l(-1) yeast. The co
      substrate yield was further enhanced by genetically engineered strains with
      reduced phosphoglucose isomerase activity and with the gene encoding alcohol
      dehydrogenase deleted. Co-substrate yields were increased 2.3-fold and 2.4-fold,
      respectively, in these strains.

PMID- 12226720
TI  - Flavin reductase coupling with two monooxygenases involved in dibenzothiophene
      desulfurization: purification and characterization from a non-desulfurizing
      bacterium, Paenibacillus polymyxa A-1.
AB  - The dibenzothiophene (DBT) desulfurizing bacterium metabolizes DBT to form 2
      hydroxybiphenyl without breaking the carbon skeleton. Of the DBT desulfurization
      enzymes, DszC and DszA catalyze monooxygenation reactions, both requiring flavin
      reductase. We searched for non-DBT-desulfurizing microorganisms producing a
      flavin reductase that couples more efficiently with DszC than that produced by
      the DBT desulfurizing bacterium Rhodococcus erythropolis D-1, and found
      Paenibacillus polymyxa A-1 to be a promising strain. The enzyme was purified to
      complete homogeneity. K(m) values for FMN and NADH were 2.1 microM and 0.57 mM,
      respectively. Flavin compounds were good substrates, some nitroaromatic compounds
      were also active, and regarding the electron donor, the activity for NADPH was
      about 1.5 times that for NADH. In the coupling assay with DszC, only FMN or
      riboflavin acted as the electron acceptor. The coupling reactions of P. polymyxa
      A-1 flavin reductase with DszC and DszA proceeded more efficiently (3.5- and 5
      fold, respectively) than those of R. erythropolis D-1 flavin reductase when
      identical enzyme activities of each flavin reductase were added to the reaction
      mixture. The result of the coupling reaction suggested that, in the microbial DBT
      desulfurization, flavin reductase from the non-DBT-desulfurizing bacterium was
      superior to that from the DBT-desulfurizing bacterium.

PMID- 12226721
TI  - Identification and heterologous expression of the cytochrome P450 oxidoreductase
      from the white-rot basidiomycete Coriolus versicolor.
AB  - A cDNA encoding cytochrome P450 oxidoreductase (CPR) from the lignin-degrading
      basidiomycete Coriolus versicolor was identified using RT-PCR. The full-length
      cDNA consisted of 2,484 nucleotides with a poly(A) tail, and contained an open
      reading frame. The G+C content of the cDNA isolated was 60%. A deduced protein
      contained 730 amino acid residues with a calculated molecular weight of 80.7 kDa.
      The conserved amino acid residues involved in functional domains such as FAD-,
      FMN-, and NADPH-binding domains, were all found in the deduced protein. A
      phylogenetic analysis demonstrated that C. versicolor CPR is significantly
      similar to CPR of the basidiomycete Phanerochaete chrysosporium and that they
      share the same major branch in the fungal cluster. A recombinant CPR protein was
      expressed using a pET/ Escherichia coli system. The recombinant CPR protein
      migrated at 81 kDa on SDS polyacrylamide gel electrophoresis. It exhibited an
      NADPH-dependent cytochrome c reducing activity.

PMID- 12226722
TI  - The mannitol dehydrogenase gene (mdh) from Leuconostoc mesenteroides is distinct
      from other known bacterial mdh genes.
AB  - The N-terminal amino acid sequences of the intact protein and three tryptic
      peptides from a 41 kDa protein purified from a commercial mannitol dehydrogenase
      (MDH) enzyme preparation of Leuconostoc mesenteroides ATCC-9135 were determined.
      Oligonucleotides deduced from these peptide sequences were used to isolate the
      putative mdh gene from L. mesenteroides using the Vectorette system. Nucleotide
      sequence analysis revealed an open reading frame (ORF1) of 1,014 bp encoding a
      putative MDH protein of 338 amino acids, and another open reading frame (ORF2)
      encoding an unknown protein of 245 amino acids. In Northern blots, a transcript
      of approximately 2.2-kb was detected with an mdh-specific probe. Mapping of the
      5'-end of the 2.2-kb transcript indicated that mdh was the first gene of the
      operon. After fusion of six histidine codons to the 3'-end of the mdh gene and
      expression in Escherichia coli M15, active MDH was isolated using HisTrap
      purification. The overexpressed enzyme showed high specificity for mannitol and
      fructose. In dot blot hybridisation, the L. mesenteroides mdh-specific probe
      bound strongly to chromosomal DNA of Leuconostoc pseudomesenteroides and weakly
      to DNA of some heterofermentative Lactobacillus strains, whereas no hybridisation
      signals were obtained with DNA derived from strains carrying characterised mdh
      genes. Furthermore, the amino acid sequence similarity between L. mesenteroides
      MDH and other known MDHs was very low, suggesting that MDHs from
      heterofermentative lactic acid bacteria form a structurally and functionally
      separate enzyme group. Interestingly, L. mesenteroides MDH shared significant
      sequence similarity with the medium-chain dehydrogenase/reductase protein family.

PMID- 12226723
TI  - Redox-mediated decolorization of synthetic dyes by fungal laccases.
AB  - Laccases from the lignin-degrading basidiomycetes Trametes versicolor, Polyporus
      pinisitus and the ascomycete Myceliophthora thermophila were found to decolorize
      synthetic dyes to different extents. Differences were attributed to the specific
      catalytic properties of the individual enzymes and to the structure of the dyes.
      Due to their higher oxidative capacities, the laccases from the two
      basidiomycetes decolorized dyes more efficiently than that of the ascomycete. The
      azo dye Direct Red 28, the indigoid Acid Blue 74 and anthraquinonic dyes were
      directly enzymatically decolorized within 16 h. The addition of 2 mM of the redox
      mediator 1-hydroxybenzotriazole further improved and facilitated the
      decolorization of all nine dyes investigated. Laccases decolorized dyes both
      individually and in complex mixtures in the presence of bentonite or immobilized
      in alginate beads. Our data suggest that laccase/mediator systems are effective
      biocatalysts for the treatment of effluents from textile, dye or printing
      industries.

PMID- 12226724
TI  - Biotransformation of p-xylene and 2,6-dimethylnaphthalene by xylene monooxygenase
      cloned from a Sphingomonas isolate.
AB  - Sphingomonas strain ASU1 was isolated from an industrial wastewater bioreactor
      and grew on 2,6-dimethylnaphthalene (2,6-DMN) as the sole carbon/energy source.
      The genes for a xylene monooxygenase were cloned from strain ASU1. Expression of
      the ASU1 xylene monooxygenase was compared to expression of the pWWO xylene
      monooxygenase in Escherichia coli. Both monooxygenases transformed p-xylene and
      2,6-DMN by initially hydroxylating one methyl group. In addition, the ASU1
      monooxygenase also hydroxylated the second methyl group on p-xylene and 2,6-DMN
      whereas the pWWO monooxygenase hydroxylated the second methyl group only on p
      xylene. Endogenous E. coli enzymes contributed to further oxidation of the
      resulting aromatic alcohols to form aromatic carboxylates.

PMID- 12226725
TI  - Overexpression of the phytase from Escherichia coli and its extracellular
      production in bioreactors.
AB  - The gene for phytase from Escherichia coli was sequenced and compared with the
      appA gene. It was found to be a mutant derivative of the appA gene. After fusion
      with a C-terminal His-tag, phytase was purified by affinity chromatography and
      the enzymatic properties were analyzed. To develop a system for overexpression
      and extracellular production of phytase in E. coli, factors affecting the
      expression and secretion such as promoter type, host strain and selection
      pressure were analyzed. Using a secretion system based on the controlled
      expression of the kil gene, the expression of phytase was improved and the enzyme
      was released into the culture medium at a high level. An effective fermentation
      strategy based on fed-batch operation was developed.

PMID- 12226726
TI  - A polymerase chain reaction-based test for Verticillium fungicola causing dry
      bubble disease on the cultivated mushroom, Agaricus bisporus.
AB  - A polymerase chain reaction (PCR)-based test is described for the specific
      detection of Verticillium fungicola var. aleophilum (Vfa), the fungal pathogen
      causing dry bubble disease on the cultivated button mushroom, Agaricus bisporus.
      PCR primers were tailored to target a 162-bp arbitrary sequence in the Vfa
      genome. In PCR amplifications using the primer pair, all of 20 isolates of Vfa
      that had been collected during a 29-year period at commercial mushroom operations
      located primarily in North America were found to generate the diagnostic 162-bp
      DNA product. Conversely, the primers failed to produce the specific amplicon with
      DNA from isolates representing 5 other species of Verticillium, the pathogenic
      subspecies V. fungicola var. fungicola from Europe, and 12 other fungal species
      commonly inhabiting mushroom compost. A protocol was designed enabling a
      confirmed diagnosis of dry bubble disease in less than 3 h. The PCR-based test
      should find application for the rapid diagnosis and detection of the fungal
      pathogen in disease management programs and, potentially, in screening for on-the
      farm sources of infection.

PMID- 12226728
TI  - Monitoring of morphological development of the arachidonic-acid-producing
      filamentous microorganism Mortierella alpina.
AB  - Morphological parameters, such as hyphal growth rate, tip formation rate, tip
      extension rate and branch formation rate, of Mortierella alpina have been
      measured using a flow-through chamber under 25 different combinations of carbon
      and nitrogen concentrations. Morphological parameters were influenced not by C/N
      ratio but by carbon concentration in the medium. Specific rates of hyphal growth
      and tip formation both remained constant at a low carbon concentration of 5 g/l.
      Tip extension rate from one tip was 60 microm tip(-1) h(-1) at a carbon
      concentration below 15 g/l, and the branching formation rate was independent of
      carbon concentration. Tip extension rate was a function of specific hyphal growth
      rate, which in turn was linearly proportional to the specific tip formation rate,
      demonstrating that tip extension rate was exponentially proportional to the
      specific tip formation rate. Branch formation rate per hyphal element remained
      unchanged even at tip extension rates lower than 60 microm tip(-1) h(-1) and at
      specific hyphal growth rates lower than 0.83 h(-1), but decreased drastically at
      higher rates of tip extension and hyphal growth.

PMID- 12226727
TI  - Use of the pAL5000 replicon in PAH-degrading mycobacteria: application for strain
      labelling and promoter probing.
AB  - Three environmental Mycobacterium strains (LB501T, LB307T and VM552) able to
      degrade anthracene, phenanthrene or pyrene, respectively, were successfully
      electroporated with pAL5000-based plasmids containing the green fluorescent
      protein (gfp) gene of Aequoria victoria under the control of the hsp60 promoter
      of Mycobacterium bovis following a slightly modified standard procedure.
      Transformants showed irregular gfp expression profiles. Four plasmid derivatives
      were constructed that contained gene promoters isolated from, and adapted to,
      gene expression in polycyclic aromatic hydrocarbon (PAH)-degrading mycobacteria.
      One derivative directed strong and homogeneous expression of GFP, allowing dual
      analysis of both GFP- and PAH-derived fluorescence as assessed by confocal laser
      scanning microscopy. The results reported here demonstrate the suitability of the
      pAL5000 replicon for the development of recombinant DNA-based studies in PAH
      degrading Mycobacterium spp.

PMID- 12226729
TI  - Optimization of medium and cultivation conditions for capsular polysaccharide
      production by Streptococcus pneumoniae serotype 23F.
AB  - The influence of medium composition and culture conditions on Streptococcus
      pneumoniae serotype 23F cultivation was investigated in order to develop an
      industrial method for polysaccharide (PS) production. Acid-hydrolyzed casein
      (AHC) and dialyzed enzymatically hydrolyzed soybean meal (EHS) were investigated
      as nitrogen sources, and the vitamin solution of Hoeprich's medium and dialyzed
      yeast extract as vitamin sources. The influence of initial glucose concentration
      was also evaluated. In flask experiments, the best nitrogen source for PS
      production was AHC; EHS yielded small amounts of PS without interfering with
      bacterial growth. Dialyzed yeast extract provided an approximately 2-fold
      increase in PS production when compared to Hoeprich's vitamin solution. In a 5-l
      bioreactor, it was observed that the pneumococcus did not grow under aerobic
      conditions, CO(2) did not increase PS yield, glucose was inhibitory above 30 g l(
      1), and the main glucose catabolism product was lactate, which had an inhibitory
      effect on cell growth. When anaerobic cultivation was performed under N(2) flow
      using the optimized medium, 240 mg l(-1) of soluble PS was obtained, which
      represents a 3-fold increase in yield as compared to that described in the
      published patent [Yavordios and Cousin (1983) European Patent 0 071515 A1].
      Application of these results would considerably simplify upstream and downstream
      processes for PS production.

PMID- 12226730
TI  - Role of electrostatic interactions in cohesion of bacterial biofilms.
AB  - Significant decreases in the apparent viscosity of a bacterial biofilm suspension
      were measured following addition of sodium, potassium, magnesium, or calcium
      salts, whereas iron salts increased the viscosity. Electrostatic interactions
      contribute to biofilm cohesion and iron cations are potent crosslinkers of the
      biofilm matrix.

PMID- 12226731
TI  - Isolation and characterization of a Trichodermastrain capable of fermenting
      cellulose to ethanol.
AB  - The direct fermentation of cellulosic biomass to ethanol has long been a desired
      goal. To this end, we screened the environment for fungal strains capable of this
      conversion when grown on minimal medium. One strain, identified as a member of
      the genus Trichoderma and designated strain A10, was isolated from cow dung and
      initially produced about 0.4 g ethanol l(-1). This strain cannot grow on any
      substrate under anaerobic conditions, but can ferment microcrystalline cellulose
      or several sugars to ethanol. Ethanol accumulation was eventually increased, by
      selection and the use of a vented fermentation flask, to 2 g l(-1) when the
      fermentation was carried out in submerged culture in minimal medium. The highest
      levels of ethanol, >5.0 g l(-1), were obtained by the fermentation of glucose.
      Little ethanol was produced by the fermentation of xylose, although other
      fermentation products such as succinate and acetate were observed. Strain A10 was
      also found to utilize (aerobically) a wide range of carbon sources. In addition,
      auxotrophic mutants were generated and used to demonstrate parasexuality by
      complementation between auxotrophs and between morphological mutants. The ability
      of this strain to use a wide variety of carbohydrates (including crystalline
      cellulose) combined with its minimal nutrient requirements and the availability
      of a genetic system suggests that the strain merits further investigation of its
      ability to convert biomass to ethanol.

PMID- 12226732
TI  - Saccharomyces bayanus var. uvarum in Tokaj wine-making of Slovakia and Hungary.
AB  - Using genetic hybridisation analysis and molecular karyotyping we revealed an
      association of Saccharomyces bayanus var. uvarum species with Tokaj wine-making.
      Along with identification of Saccharomyces strains isolated by E. Minarik in
      Slovakia, the composition of Tokaj populations in Hungary was studied. Twenty
      eight Hungarian Saccharomyces strains were analysed in terms of karyotype. The
      majority of strains belong to S. bayanus var. uvarum. Two non-identified
      Saccharomyces strains were found to be polyploid according to their complex
      karyotype patterns.

PMID- 12226733
TI  - Quantitative and rapid detection of the trichloroethylene-degrading bacterium
      Methylocystis sp. M in groundwater by real-time PCR.
AB  - We developed a method based on real-time PCR for the specific and rapid
      enumeration of a trichloroethylene-degrading methanotroph, Methylocystis sp. M,
      with the aim of monitoring the strain in groundwater. A primer set designed from
      the nucleotide sequence of the mmoC gene of a soluble methane monooxygenase
      (sMMO) gene cluster from Methylocystis sp. M was specific to amplify the DNA
      region from the strain and no PCR products were amplified with the sMMO gene
      clusters from six other methanotroph strains. The real-time PCR reliably
      quantified Methylocystis sp. M over at least five orders of magnitude (5x10(6) to
      5x10(2 )cells/PCR tube, or 2x10(8) to 2x10(4 )cells/ml). Five cells of
      Methylocystis sp. M per PCR tube (2x10(2 )cells/ml) were detectable when the
      cells were suspended in distilled water. The concomitant presence of other
      methanotrophs in samples did not affect the reliability of enumeration; and
      recovery of the cells with a membrane filter enabled us to quantify cells of the
      strain in groundwater. This quantification procedure was completed within 3 h,
      including preparation time of environmental samples. We conclude that real-time
      PCR using the mmoC primer set can be used practically to analyze the behavior of
      Methylocystis sp. M at bioremediation sites.

PMID- 12226734
TI  - Isolation and characterization of a moderate thermophile, Mycobacterium phlei
      GTIS10, capable of dibenzothiophene desulfurization.
AB  - An organism, identified as Mycobacterium phlei GTIS10, was isolated based on its
      ability to use dibenzothiophene (DBT) as a sole source of sulfur for growth at 30
      52 degrees C. Similar to other biodesulfurization-competent organisms, M. phlei
      GTIS10 converts DBT to 2-hydroxybiphenyl (2-HBP), as detected by HPLC. The
      specific desulfurization activity of the 50 degrees C M. phlei GTIS10 culture was
      determined to be 1.1+/-0.07 micromol 2-HBP min(-1) (g dry cell)(-1). M. phlei
      GTIS10 can also utilize benzothiophene and thiophene as sulfur sources for
      growth. The dszABC operon of M. phlei GTIS10 was cloned and sequenced and was
      found to be identical to that of Rhodococcus erythropolis IGTS8. The presence of
      the R. erythropolis IGTS8 120-kb plasmid pSOX, which encodes the dszABC operon,
      has been demonstrated in M. phlei GTIS10. Even though identical dsz genes are
      contained in both cultures, the temperature at which resting cells of R.
      erythropolisIGTS8 reach the highest rate of DBT metabolism is near 30 degrees C
      whereas the temperature that shows the highest activity in resting cell cultures
      of M. phlei GTIS10 is near 50 degrees C, and activity is detectable at
      temperatures as high as 57 degrees C. In M. phlei GTIS10, the rate-limiting step
      in vivo appears to be the conversion of DBT to dibenzothiophene sulfone catalyzed
      by the product of the dszC gene, DBT monooxygenase. The thermostability of
      individual desulfurization enzymes was determined and 2-hydroxybiphenyl-2
      sulfinate sulfinolyase, encoded by dszB, was found to be the most thermolabile.
      These results demonstrate that the thermostability of individual enzymes
      determined in vitro is not necessarily a good predictor of the functional
      temperature range of enzymes in vivo.

PMID- 12226735
TI  - Gentamicin as gene therapy.

PMID- 12226736
TI  - JMM---past and present. Chromosomes and cancer: Theodor Boveri's predictions 100
      years later.

PMID- 12226737
TI  - Cathelicidins, essential gene-encoded mammalian antibiotics.
AB  - Cathelicidins are a class of gene-encoded antibiotics found exclusively in
      mammals. In vitro and in vivo studies indicate they are effector molecules of
      mammalian innate immunity that can provide a first line of defense against an
      array of micro-organisms. Additional functions are described for some members of
      this class of antimicrobial peptides including chemotactic activity, mitogenesis,
      and angiogenesis. Therefore these peptides are considered to be multifunctional
      effector molecules. This review discusses recent progress in cathelicidin
      research and the functional properties of cathelicidins. Current work in this
      field suggests that understanding this component of the mammalian innate immune
      system and related natural antibiotic peptides offer an opportunity for the
      development of novel therapeutic agents with which to battle the continued
      problem of antimicrobial resistance.

PMID- 12226738
TI  - A role for hypoxia and hypoxia-inducible transcription factors in tumor
      physiology.
AB  - Cumulative acquisition of genetic alterations affecting oncogenes or tumor
      suppressor genes may select for tumor cell clones with enhanced proliferation and
      survival potential. As a result oxygen and nutrient consumption increases,
      leading to a tumor microenvironment characterized by low oxygen tension, low
      glucose levels, and an acidic pH. Hypoxia-inducible transcription factors (HIF)
      are activated in response to hypoxia, apparently via reduced activity of the
      recently identified class of 2-oxoglutarate dependent oxygenases, as well as
      various tumor specific genetic alterations. A widespread HIF activation can be
      observed in a variety of malignant tumors. The HIF system induces adaptive
      responses including angiogenesis, glycolysis, and pH regulation which confer
      increased resistance towards the hostile tumor microenvironment. Apart from
      protumorigenic the wide-ranging HIF pathway may also have antitumorigenic
      components, which might, however, be counteracted by specific genetic mechanisms.
      Thus mounting evidence suggests that the HIF system plays a decisive role in
      tumor physiology and progression. Moreover, recent insight into this pathway has
      opened novel and potentially selective therapeutic approaches.

PMID- 12226739
TI  - Endothelial-derived lipoprotein lipase is bound to postprandial triglyceride-rich
      lipoproteins and mediates their hepatic clearance in vivo.
AB  - Lipoprotein lipase (LPL) is the key enzyme in the intravascular hydrolysis of
      triglyceride-rich lipoproteins (TRL). Furthermore, it has been shown that
      inactive LPL can mediate cellular binding and uptake of TRL in vitro. This study
      investigated whether LPL is bound to postprandial human TRL in vivo, and whether
      it plays a role in the hepatic clearance of these particles independent of its
      catalytic activity. LPL was found to bind to postprandial TRL in preheparin
      plasma of healthy young men. To study the effect of inactive LPL on particle
      uptake, TRL isolated from patients with inactive LPL (LPL or apoC-II mutations)
      were used before and after heparin administration. These model particles allow
      one to study the bridging effect of LPL independent of its enzymatic activity.
      Organ uptake studies with these particles in mice revealed that inactive LPL
      increases the hepatic clearance of TRL significantly while uptake into other
      organs remains largely unaffected. Further evidence that endothelial-derived LPL
      directs TRL to the liver in vivo was gained with transgenic mice that express
      inactive LPL exclusively in muscle, revealing greater hepatic uptake than in wild
      type mice. In conclusion, these data demonstrate for the first time that LPL is a
      structural component of postprandial TRL which facilitates hepatic TRL clearance
      from the circulation independent of its catalytic function.

PMID- 12226740
TI  - Adenovirus-mediated intratumoral lymphotactin gene transfer potentiates the
      antibody-targeted superantigen therapy of cancer.
AB  - Bacterial superantigens are extremely potent activators of murine and human T
      lymphocytes. To engineer superantigens for cancer immunotherapy, staphylococcal
      enterotoxin A (SEA) was genetically fused to the Fab region of the human colon
      carcinoma-reactive monoclonal antibody (mAb) C215. Fusion protein C215Fab-SEA can
      trigger cytotoxic T cells against C215 antigen positive tumor cells and induce
      tumor-suppressive cytokines. However, the antitumor effect of C215Fab-SEA is
      often not satisfactory because of T cell deletion after activation and failure to
      induce potent CTL activity after repeated administration. Lymphotactin (Lptn) is
      a potent chemoattractant for T cells and NK cells. To improve the therapeutic
      efficacy of fusion protein C215Fab-SEA we investigated in this study the
      antitumor responses elicited by combination of C215Fab-SEA and adenovirus
      mediated intratumoral Lptn gene transfer in the preestablished C215 antigen
      expressing B16 melanoma murine model. More significant inhibition of tumor growth
      and prolonged survival time were observed in tumor-bearing mice that received
      combined therapy of C215Fab-SEA and Ad-Lptn than those of mice treated with
      C215Fab-SEA or Ad-Lptn alone. The highest CTL activity of tumor-bearing mice was
      induced after combined therapy. Intratumoral coadministration of C215Fab-SEA and
      Ad-Lptn augmented splenic NK activity of tumor-bearing mice most markedly. Our
      data demonstrate that the in vivo antitumor effect of C215Fab-SEA immunotherapy
      is potentiated significantly by combination with intratumoral Lptn gene transfer
      through more efficient induction of specific and nonspecific antitumor immune
      responses.

PMID- 12226741
TI  - Aminoglycoside suppression of a premature stop mutation in a Cftr-/- mouse
      carrying a human CFTR-G542X transgene.
AB  - Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic
      fibrosis transmembrane conductance regulator (CFTR) protein. Since approximately
      5% of all mutant CF alleles are stop mutations, it can be calculated that
      approximately 10% of CF patients carry a premature stop mutation in at least one
      copy of the CFTR gene. Certain ethnic groups, such as the Ashkenazi Jewish
      population, carry a much higher percentage of CF stop mutations. Consequently, a
      therapeutic strategy aimed at suppressing this class of mutation would be highly
      desirable for the treatment of this common genetic disease. We have shown
      previously that aminoglycoside antibiotics can suppress premature stop mutations
      in the CFTR gene in a bronchial epithelial cell line [Nat Med (1997) 3:1280]. To
      address whether aminoglycosides can suppress a CFTR premature stop mutation in an
      animal model, we constructed a transgenic mouse with a null mutation in the
      endogenous CFTR locus (Cftr-/-) that also expressed a human CFTR-G542X cDNA under
      control of the intestinal fatty acid binding protein promoter. We then
      investigated whether the daily administration of the aminoglycoside antibiotics
      gentamicin or tobramycin could restore the expression of a detectable level of
      CFTR protein. Immunofluorescence staining of intestinal tissues from Cftr-/-
      hCFTR-G542X mice revealed that gentamicin treatment resulted in the appearance of
      hCFTR protein at the apical surface of the glands of treated mice. Weaker
      staining was also observed in the intestinal glands following tobramycin
      treatment. Short-circuit current measurements made on intestinal tissues from
      these mice demonstrated that a significant number of positive cAMP-stimulated
      transepithelial chloride current measurements could be observed following
      gentamicin treatment (P=0.008) and a near significant number following tobramycin
      treatment (P=0.052). When taken together, these results indicate that gentamicin,
      and to a lesser extent tobramycin, can restore the synthesis of functional hCFTR
      protein by suppressing the hCFTR-G542X premature stop mutation in vivo.

PMID- 12226742
TI  - Association of the endothelial nitric oxide synthase gene polymorphism with risk
      of coronary artery disease and myocardial infarction in middle-aged men.
AB  - Nitric oxide (NO), formed by endothelial constitutive nitric oxide synthase
      (eNOS) maintains endothelium-dependent vasodilatation and also mediates
      antithrombotic actions. The eNOS gene harbours a common polymorphism in intron 4
      (4a/b), and some clinical studies have suggested an association of the rare a
      allele with coronary artery disease (CAD) and myocardial infarction (MI).
      However, contradictory results have also been reported. We studied associations
      of eNOS polymorphism with CAD and MI in two prospective autopsy series comprising
      altogether 700 Caucasian Finnish men, who died suddenly. In ANCOVA, no
      significant differences in areas of atherosclerotic lesions and coronary stenosis
      percentages were found between men carrying the a-allele (ba+aa) compared with
      those homozygous for the b-allele. Subjects with the a-allele had significantly
      lower risk of MI (odds ratio 0.44, 95% confidence interval 0.25-0.77, P=0.004)
      compared with those carrying the bb genotype. Men with the a-allele also tended
      to have coronary thrombosis less often (odds ratio 0.43, 95% confidence interval
      0.18-1.01, P=0.055). The eNOS gene 4a/b polymorphism was not associated with the
      extent of coronary atherosclerosis, but the a-allele of the variant seems to
      protect to some degree against the development of MI.

PMID- 12226744
TI  - A key role of the hSNF5/INI1 tumour suppressor in the control of the G1-S
      transition of the cell cycle.
AB  - The hSNF5/INI1 gene encodes a member of the SWI/SNF chromatin remodelling
      complexes. It was recently identified as a tumour suppressor gene mutated in
      sporadic and hereditary Malignant Rhabdoid Tumours (MRT). However, the role of
      hSNF5/INI1 loss-of-function in tumour development is still unknown. Here, we show
      that the ectopic expression of wild-type hSNF5/INI1, but not that of truncated
      versions, leads to a cell cycle arrest by inhibiting the entry into S phase of
      MRT cells. This G1 arrest is associated with down-regulation of a subset of E2F
      targets including cyclin A, E2F1 and CDC6. This arrest can be reverted by
      coexpression of cyclin D1, cyclin E or viral E1A, whereas it cannot be
      counteracted by pRB-binding deficient E1A mutants. Moreover, hSNF5/INI1 is not
      able to arrest cells lacking a functional pRB. These observations suggest that
      the hSNF5/INI1-induced G1 arrest is dependent upon the presence of a functional
      pRB. However, the observation that a constitutively active pRB can efficiently
      arrest MRT cells indicates that hSNF5/INI1, at the difference of the ATPase
      subunits of the SWI/SNF complex, is dispensable for pRB function. Altogether,
      these data show that hSNF5/INI1 is a potent regulator of the entry into S phase,
      an effect that may account for its tumour suppressor role.

PMID- 12226743
TI  - A clinical protocol for treatment of canine mammary tumors using encapsulated,
      cytochrome P450 synthesizing cells activating cyclophosphamide: a phase I/II
      study.

PMID- 12226745
TI  - p42/p44 MAPKs are intracellular targets of the CDK inhibitor purvalanol.
AB  - Chemical inhibitors of cyclin-dependent kinases (CDKs) have a great therapeutic
      potential against various proliferative and neurodegenerative disorders.
      Intensive screening of a combinatorial chemistry library of 2,6,9-trisubstituted
      purines has led to the identification of purvalanol, one of the most potent and
      selective CDK inhibitors to date. In preliminary studies, this compound
      demonstrates definite anti-mitotic properties, consistent with its nanomolar
      range efficiency towards purified CDK1 and CDK2. However, the actual
      intracellular targets of purvalanol remain to be identified, and a method for the
      determination of its in vivo selectivity was developed. In this technique, cell
      extracts were screened for purvalanol-interacting proteins by affinity
      chromatography on immobilized inhibitor. In addition to CDK1, p42/p44 MAPK were
      found to be two major purvalanol-interacting proteins in five different mammalian
      cell lines (CCL39, PC12, HBL100, MCF-7 and Jurkat cells), suggesting the
      generality of the purvalanol/p42/p44 MAPK interaction. The Chinese hamster lung
      fibroblast cell line CCL39 was used as a model to investigate the anti
      proliferative properties of purvalanol. The compound inhibited cell growth with a
      GI(50) value of 2.5 microM and induced a G2/M block when added to exponentially
      growing cells. It did not appear to trigger massive activation of caspase. We
      next tested whether CDKs and p42/p44 MAPK were actually targeted by the compound
      in vivo. p42/p44 MAPK activity was visualized using an Elk-Gal4 luciferase
      reporter system and CDK1 activity was detected by the phosphonucleolin level.
      When cells were treated with purvalanol, p42/p44 MAPK and CDK1 activities were
      inhibited in a dose-dependent manner. Furthermore, purvalanol inhibited the
      nuclear accumulation of p42/p44 MAPK, an event dependent on the catalytic
      activity of these kinases. We conclude that the anti-proliferative properties of
      purvalanol are mediated by inhibition of both p42/p44 MAPK and CDKs. These
      observations highlight the potency of moderate selectivity compounds and
      encourage the search for new therapeutics which simultaneously target distinct
      but relevant pathways of cell proliferation.

PMID- 12226746
TI  - Xenopus H-RasV12 promotes entry into meiotic M phase and cdc2 activation
      independently of Mos and p42(MAPK).
AB  - In the Xenopus oocyte, progesterone triggers M phase Promoting Factor (MPF)
      activation in a protein synthesis dependent manner. Although the synthesis of the
      p42(MAPK) activator Mos appears to be required for MPF activation, p42(MAPK)
      activity has been shown to be dispensable. To clarify this paradox, we attempted
      to activate the p42(MAPK) pathway independently of Mos synthesis by cloning and
      using Xenopus H-Ras in the oocyte. We demonstrate that the injection of the
      constitutively active Xe H-RasV12 mutant induces p42(MAPK) and MPF activation
      through two independent pathways. Xe H-RasV12 induces only a partial activation
      of p42(MAPK) when protein synthesis and MPF activation are prevented. A full
      level of p42(MAPK) activation is reached when MPF is activated and Mos is
      present. In contrast, MPF activation induced by Xe H-RasV12 is achieved
      independently of Mos synthesis and p42(MAPK) activation but still depends on
      protein synthesis. Therefore, the amphibian oocyte represents a new model system
      to analyse an original H-Ras pathway ending to MPF activation and distinct from
      the p42(MAPK) pathway. The identification of the proteins synthesized in response
      to Xe H-RasV12 and required for MPF activation, represents an important clue in
      understanding the mechanism of progesterone action.

PMID- 12226747
TI  - Menin uncouples Elk-1, JunD and c-Jun phosphorylation from MAP kinase activation.
AB  - Menin, a nuclear protein encoded by the tumor suppressor gene MEN1, interacts
      with the AP-1 transcription factor JunD and inhibits its transcriptional
      activity. In addition, overexpression of Menin counteracts Ras-induced
      tumorigenesis. We show that Menin inhibits ERK-dependent phosphorylation and
      activation of both JunD and the Ets-domain transcription factor Elk-1. We also
      show that Menin represses the inducible activity of the c-fos promoter.
      Furthermore, Menin expression inhibits Jun N-terminal kinase (JNK)-mediated
      phosphorylation of both JunD and c-Jun. Kinase assays show that Menin
      overexpression does not interfere with activation of either ERK2 or JNK1,
      suggesting that Menin acts at a level downstream of MAPK activation. An N
      terminal deletion mutant of Menin that cannot inhibit JunD phosphorylation by
      JNK, can still repress JunD phosphorylation by ERK2, suggesting that Menin
      interferes with ERK and JNK pathways through two distinct inhibitory mechanisms.
      Taken together, our data suggest that Menin uncouples ERK and JNK activation from
      phosphorylation of their nuclear targets Elk-1, JunD and c-Jun, hence inhibiting
      accumulation of active Fos/Jun heterodimers. This study provides new molecular
      insights into the tumor suppressor function of Menin and suggests a mechanism by
      which Menin may interfere with Ras-dependent cell transformation and oncogenesis.

PMID- 12226748
TI  - Inactivation of Apc perturbs mammary development, but only directly results in
      acanthoma in the context of Tcf-1 deficiency.
AB  - Apc (adenomatous polyposis coli) encodes a tumour suppressor gene that is mutated
      in the majority of colorectal cancers. Recent evidence has also implicated Apc
      mutations in the aetiology of breast tumours. Apc is a component of the canonical
      Wnt signal transduction pathway, of which one target is Tcf-1. In the mouse,
      mutations of both Apc and Tcf-1 have been implicated in mammary tumorigenesis. We
      have conditionally inactivated Apc in both the presence and absence of Tcf-1 to
      examine the function of these genes in both normal and neoplastic development.
      Mice harbouring mammary-specific mutations in Apc show markedly delayed
      development of the mammary ductal network. During lactation, the mice develop
      multiple metaplastic growths which, surprisingly, do not spontaneously progress
      to neoplasia up to a year following their induction. However, additional
      deficiency of Tcf-1 completely blocks normal mammary development and results in
      acanthoma.

PMID- 12226749
TI  - reaper and bax initiate two different apoptotic pathways affecting mitochondria
      and antagonized by bcl-2 in Drosophila.
AB  - bcl-2 was the first regulator of apoptosis shown to be involved in oncogenesis.
      Subsequent studies in mammals, in the nematode and in Drosophila revealed wide
      evolutionary conservation of the regulation of apoptosis. Although dbok/debcl, a
      member of the bcl-2 gene family described in Drosophila, shows pro-apoptotic
      activities, no anti-apoptotic bcl-2 family gene has been studied in Drosophila.
      We have previously reported that the human anti-apoptotic gene bcl-2 is
      functional in Drosophila, suggesting that the fruit fly shares regulatory
      mechanisms with vertebrates and the nematode, involving anti-apoptotic members of
      the bcl-2 family. We now report that bcl-2 suppresses rpr-induced apoptosis in
      Drosophila. Additionally, we have compared features of bax- and rpr-induced
      apoptosis. Flow cytometry analysis of wing disc cells demonstrate that both
      killers trigger mitochondrial defects. Interestingly, bcl-2 suppresses both bax-
      and rpr-induced mitochondrial defects while the caspase-inhibitor p35 is specific
      to the rpr pathway. Finally, we show that the inhibition of apoptosis by bcl-2 is
      associated with the down-regulation of rpr expression.

PMID- 12226750
TI  - The radioprotective effect of the 24 kDa FGF-2 isoform in HeLa cells is related
      to an increased expression and activity of the DNA dependent protein kinase (DNA
      PK) catalytic subunit.
AB  - We previously reported that overexpression of the 24 kDa basic fibroblast factor
      (or FGF-2) isoform provides protection from the cytotoxic effect of ionizing
      radiation (IR). DNA double-strand breaks (DSB), the IR-induced lethal lesions,
      are mainly repaired in human cells by non-homologous end joining system (NHEJ).
      NHEJ reaction is dependent on the DNA-PK holoenzyme (composed of a regulatory sub
      unit, Ku, and a catalytic sub-unit, DNA-PKcs) that assembles at sites of DNA
      damage. We demonstrated here that the activity of DNA-PK was increased by twofold
      in two independent radioresistant cell lines, HeLa 3A and CAPAN A3, over
      expressing the 24 kDa FGF-2. This increase was associated with an overexpression
      of the DNA-PKcs without modification of Ku expression or activity. This
      overexpression was due to an up-regulation of the DNA-PKcs gene transcription by
      the 24 kDa FGF-2 isoform. Finally, HeLa 3A cells exhibited the hallmarks of
      phenotypic changes associated with the overexpression of an active DNA-PKcs.
      Indeed, a faster repair rate of DSB and sensitization to IR by wortmannin was
      observed in these cells. Our results represent the characterization of a new
      mechanism of control of DNA repair and radioresistance in human tumor cells
      dependent on the overproduction of the 24 kDa FGF-2 isoform.

PMID- 12226751
TI  - Quantitative real-time PCR identifies a critical region of deletion on 22q13
      related to prognosis in oral cancer.
AB  - Quantitative real time PCR was performed on genomic DNA from 40 primary oral
      carcinomas and the normal adjacent tissues. The target genes ECGFB, DIA1, BIK,
      and PDGFB and the microsatellite markers D22S274 and D22S277, mapped on 22q13,
      were selected according to our previous loss of heterozygosity findings in head
      and neck tumors. Quantitative PCR relies on the comparison of the amount of
      product generated from a target gene and that generated from a disomic reference
      gene (GAPDH-housekeeping gene). Reactions have been performed with normal control
      in triplicates, using the 7700 Sequence Detection System (PE Applied Biosystems).
      Losses in the sequences D22S274 (22q13.31) and in the DIA1 (22q13.2-13.31) gene
      were detected in 10 out of 40 cases (25%) each. Statistically significant
      correlations were observed for patients with relative copy number loss of the
      marker D22S274 and stages T3-T4 of disease (P=0.025), family history of cancer
      (P=0.001), and death (P=0.021). Relative copy number loss involving the DIA1 gene
      was correlated to family history of cancer (P<0.001), death (P=0.002), and
      consumption of alcohol (P=0.026). Log-rank test revealed a significant decrease
      in survival (P=0.0018) for patients with DIA1 gene loss. Relative copy number
      losses detected in these sequences may be related to disease progression and a
      worse prognosis in patients with oral cancer.

PMID- 12226752
TI  - A scaffold protein in the c-Jun N-terminal kinase signaling pathway is associated
      with focal adhesion kinase and tyrosine-phosphorylated.
AB  - Focal adhesion kinase (FAK) becomes activated and tyrosine-phosphorylated in
      response to cell adhesion to extracellular matrix proteins in a variety of cell
      types, and associates with a number of signaling molecules, structural proteins,
      and beta integrin cytoplasmic domains. Here we demonstrated that c-Jun N-terminal
      kinase (JNK)/stress activated protein kinase-associated protein 1 (JSAP1), a
      scaffold factor in the mitogen-activated protein kinase (MAPK) cascades, forms a
      complex with the N-terminus of FAK. The complex formation was further stimulated
      by c-Src, in which JSAP1 was tyrosine-phosphorylated and other FAK/Src signaling
      molecules were recruited. Fibronectin (FN) stimulation of cells expressing JSAP1
      induced its tyrosine phosphorylation concomitant with association with FAK.
      Expression of JSAP1 in Hela cells facilitated formation of well-organized focal
      contacts and actin stress fibers, and promoted cell spreading onto FN. Taken
      together, these results suggest that JSAP1 is involved an integrin-mediated
      signaling pathway through FAK/Src by recruiting other signaling molecules,
      resulting in promotion of cell spreading onto FN.

PMID- 12226753
TI  - E2F activity is essential for survival of Myc-overexpressing human cancer cells.
AB  - Effective cell cycle completion requires both Myc and E2F activities. However,
      whether these two activities interact to regulate cell survival remains to be
      tested. Here we have analysed survival of inducible c-Myc-overexpressing cell
      lines derived from U2OS human osteosarcoma cells, which carry wild-type pRb and
      p53 and are deficient for p16 and ARF expression. Induced U2OS-Myc cells neither
      underwent apoptosis spontaneously nor upon reconstitution of the ARF-p53 axis
      and/or serum-starvation. However, they died massively when concomitantly exposed
      to inhibitors of E2F activity, including a constitutively active pRb (RbDeltacdk)
      mutant, p16, a stable p27 (p27T187A) mutant, a dominant-negative (dn) CDK2, or
      dnDP-1. Similar apoptotic effect was observed upon down-modulation of endogenous
      E2Fs through overexpression of E2F binding site oligonucleotides in U2OS-Myc
      cells, upon expression of RbDeltacdk or dnDP-1 in the Myc-amplified HL-60 (ARF-;
      p53-) human leukemia cells, and upon co-transfection of Myc and RbDeltacdk in
      SAOS-2 (ARF+; p53-) human osteosarcoma cells but not in human primary
      fibroblasts. Consistent with these results, a dnp53 mutant did not abrogate the
      Myc-induced apoptotic phenotype, which instead strictly depended on caspase-3
      like proteases and on Myc transcriptional activity. Our data indicate that in
      contrast to normal cells, Myc-overexpressing human cancer cells need E2F activity
      for their survival, regardless of their ARF and p53 status, a notion that may
      have important implications for antineoplastic treatment strategies.

PMID- 12226754
TI  - The function of multiple IkappaB : NF-kappaB complexes in the resistance of
      cancer cells to Taxol-induced apoptosis.
AB  - The Rel/NF-kappaB transcription factors play a key role in the regulation of
      apoptosis and in tumorigenesis by controlling the expressions of specific genes.
      To determine the role of the constitutive activity of RelA in tumorigenesis, we
      generated pancreatic tumor cell lines that express a dominant negative mutant of
      IkappaBalpha (IkappaBalphaM). In this report, we show that the inhibition of
      constitutive NF-kappaB activity, either by ectopic expression of IkappaBalphaM or
      by treating the cells with a proteasome inhibitor PS-341 which blocks
      intracellular degradation of IkappaBalpha proteins, downregulates the expression
      of bcl-xl. We identified two putative NF-kappaB binding sites (kappaB/A and B) in
      the bcl-xl promoter and found that these two sites interact with different NF
      kappaB proteins. p65/p50 heterodimer interacts with kappaB/A site whereas p50/p50
      homodimer interacts with kappaB/B. The bcl-xl promoter reporter gene assays
      reveal that NF-kappaB dependent transcriptional activation is mainly mediated by
      kappaB/A site, indicating that bcl-xl is one of the downstream target genes
      regulated by RelA/p50. Both IkappaBalphaM and PS-341 completely abolish NF-kappaB
      DNA binding activity; however, PS-341, but not ectopic expression of
      IkappaBalphaM, sensitized cells to apoptosis induced by Taxol. This is due to the
      Taxol-mediated reactivation of RelA through phosphorylation and degradation of
      IkappaBbeta and the re-expression of NF-kappaB regulated bcl-xl gene in these
      cancer cells as ectopic expression of the bcl-xl gene confers resistance to Taxol
      induced apoptosis in PS-341 sensitized cells. These results demonstrate the
      important function of various NF-kappaB/IkappaB complexes in regulating anti
      apoptotic genes in response to apoptotic stimuli, and they raise the possibility
      that NF-kappaB : IkappaBalpha and NF-kappaB : IkappaBbeta complexes are regulated
      by different upstream activators, and that NF-kappaB plays a key role in
      pancreatic tumorigenesis.

PMID- 12226755
TI  - The mechanism involved in the regulation of phospholipase Cgamma1 activity in
      cell migration.
AB  - Activation of the enzyme phospholipase C (PLC) leads to the formation of second
      messengers inositol 1,4,5-trisphosphate and diacylglycerol. Tyrosine kinase
      receptors activate this reaction through PLCgamma isoenzymes. PLCgamma activity
      involves its activation with, and phosphorylation by, receptor tyrosine kinases.
      Recently, it has been shown that phosphoinositide 3-kinase (PI 3-K) may regulate
      PLCgamma activity through the interaction of the PI 3-K product
      phosphatidylinositol 3,4,5-trisphosphate (PtdIns-3,4,5-P(3)) and the PLCgamma
      pleckstrin homology (PH) domain. In an effort to understand the signalling
      pathway that involves PI 3-K regulation of PLCgamma, we found that EGF induces a
      PI 3-K-dependent translocation of PLCgamma1 at the leading edge of migrating
      cells in a wound healing assay. Similarly, the isolated PH, but not the Src
      homology (SH) domains, N-SH2 or SH3, of PLCgamma1, translocates at the leading
      edge. Our experiments also showed that stable PH PLCgamma1 expression blocks
      epidermal growth factor (EGF)- and serum-induced cell motility and increases cell
      adhesion in MDA-MB-231 cells. This may suggest that influence of PI 3-K on
      PLCgamma1 could be relevant in cell migration, where PLCgamma1 seems to play a
      key role by modulating a series of events involved in actin polymerization.

PMID- 12226756
TI  - Expression of RALT, a feedback inhibitor of ErbB receptors, is subjected to an
      integrated transcriptional and post-translational control.
AB  - Over-expression studies have demonstrated that RALT (receptor associated late
      transducer) is a feedback inhibitor of ErbB-2 mitogenic and transforming signals.
      In growth-arrested cells, expression of endogenous RALT is induced by mitogenic
      stimuli, is high throughout mid to late G1 and returns to baseline as cells move
      into S phase. Here, we show that physiological levels of RALT effectively
      suppress ErbB-2 mitogenic signals. We also investigate the regulatory mechanisms
      that preside to the control of RALT expression. We demonstrate that
      pharmacological ablation of extracellular signal-regulated kinase (ERK)
      activation leads to blockade of RALT expression, unlike genetic and/or
      pharmacological interference with the activities of PKC, Src family kinases, p38
      SAPK and PI-3K. Tamoxifen-dependent activation of an inducible Raf : ER chimera
      was sufficient to induce RALT expression. Thus, activation of the Ras-Raf-ERK
      pathway is necessary and sufficient to drive RALT expression. The RALT protein is
      labile and was found to accumulate robustly upon pharmacological inhibition of
      the proteasome. We were able to detect ubiquitin-conjugated RALT species in
      living cells, suggesting that ubiquitinylation targets RALT for proteasome
      dependent degradation. Such an integrated transcriptional and post-translational
      control is likely to provide RALT with the ability to fluctuate timely in order
      to tune ErbB signals.

PMID- 12226757
TI  - Cell transformation by v-Jun deactivates ERK MAP kinase signalling.
AB  - Previous studies have shown that v-Jun accelerates G1 progression and enables
      cells to sustain S phase entry in the absence of serum growth factors. Since
      growth factor-dependent ERK MAP kinase signalling plays an important role in
      regulating the G1/S transition, we investigated whether aberrant ERK regulation
      might contribute to cell cycle deregulation by v-Jun. Contrary to expectation, we
      find that cells transformed by v-Jun exhibit a profound reduction in the basal
      level of active, dual-phosphorylated ERK. In addition, ERK becomes refractory to
      stimulation by a subset of agonists including serum, LPA, and EGF, but remains
      partially responsive to the phorbol ester, TPA. Biochemical analysis indicates
      that these defects are attributable to a combination of inefficient signal
      propagation between Ras and Raf within the ERK pathway and increased tonic
      deactivation by MAP kinase phosphatases. Taken together, these results
      demonstrate that cell transformation by v-Jun induces alterations in cell
      physiology which antagonize ERK signalling at multiple levels. The potential
      significance of this phenotype for oncogenesis by v-Jun is discussed.

PMID- 12226758
TI  - Comprehensive analysis of the gene expression profiles in human gastric cancer
      cell lines.
AB  - Gastric adenocarcinoma is one of the major malignancies worldwide. Gastric cell
      lines have been widely used as the model to study the genetics, pharmacology and
      biochemistry of gastric cancers. Here we describe a comprehensive survey of the
      gene expression profiles of 12 gastric carcinoma cell lines, using cDNA
      microarray with 43 000 clones. For comparison, we also explored the gene
      expression patterns of 15 cell lines derived from lymphoid, endothelial, stromal
      and other epithelial cancers. Expression levels of specific genes were validated
      through comparison to protein expression by immunohistochemistry using cell block
      arrays. We found sets of genes whose expression corresponds to the molecular
      signature of each cell type. In the gastric cancer cell lines, apart from genes
      that are highly expressed corresponding to their common epithelial origin from
      the gastrointestinal tract, we found marked heterogeneity among the gene
      expression patterns of these cell lines. Some of the heterogeneity may reflect
      their underlying molecular characteristics or specific differentiation program.
      Two putative gastric carcinoma cell lines were found to be B-cell lymphoma, and
      another one had no epithelial specific gene expression and hence was of doubtful
      epithelial origin. These cell lines should no longer be used in gastric carcinoma
      research. In conclusion, our gene expression database can serve as a powerful
      resource for the study of gastric cancer using these cell lines.

PMID- 12226760
TI  - [Gas: "Acoustic key" to the diagnosis].
AB  - Sonography is frequently used as the first-line technology to evaluate patients
      with acute abdominal disorders as well as for the exploration of abnormalities of
      superficial structures. However, gas often interferes with sonographic
      examination. This illustrated article describes the spectrum of sonographic
      appearances of various abnormal location of gas collections as a key for definite
      diagnosis.

PMID- 12226761
TI  - [Epiploic appendagitis: sonographic findings in 28 cases].
AB  - AIM: To investigate the sonographic signs of epiploic appendagitis in a larger
      number of patients and to add new details. PATIENTS AND METHODS: Over a period of
      approximately 8 years 28 patients were sonographically diagnosed to have epiploic
      appendagitis. The following sonographic signs were investigated: echogenicity of
      the lesion; compressibility; shape of the lesion; adherence to the anterior
      abdominal wall; peripheral rim; central hypoechoic line; thickening of the
      colonic wall. In 11 of these patients colour Doppler sonography was performed. In
      addition all 28 patients underwent CT. RESULTS: In 28/28 cases (100 %) a
      moderately hyperechoic, ovoid, non-compressible mass adjacent to the colon was
      demonstrated. The mass was surrounded by a hypoechoic rim in 20 cases (71 %) and
      was fixed to the abdominal wall in 26/28 cases (93 %). Five cases (18 %) revealed
      a central hypoechoic line, and slight thickening of the colonic wall was visible
      in 2 cases (7 %). In those cases where colour Doppler sonography was performed,
      colour flow was absent in the central part of the lesion. In the peripheral zone
      slightly increased colour flow was demonstrable in 9/11 cases. CONCLUSION:
      Epiploic appendagitis has a characteristic sonographic appearance with a
      moderately hyperechoic, ovoid, non-compressible lesion adjacent to the colon and
      adherent to the abdominal wall. The mass is frequently surrounded by a hypoechoic
      rim. Colour Doppler sonography shows a central avascular area and slightly
      increased colour flow in the peripheral zone.

PMID- 12226762
TI  - Comparison of B-mode and conventional colour/power Doppler ultrasound, contrast
      enhanced Doppler ultrasound and spiral CT in the diagnosis of focal lesions of
      the liver: Results of a multicentre study.
AB  - AIM: In patients with lesions of the liver we compared diagnoses based on
      different methods of ultrasound as well as spiral CT with the final diagnosis
      reached at the time of the patient's discharge from hospital. METHOD: From
      records of a prospective multicentre study including 90 liver lesions
      investigated with B-mode baseline and conventional colour/power Doppler
      ultrasound, contrast-enhanced colour/power Doppler ultrasound and spiral-CT, we
      evaluated only those where diagnoses for all modalities were available, and where
      the diagnosis at discharge comprising all clinical, laboratory and imaging data
      as well as histologic proof was at least "highly probable". RESULTS: 60 lesions
      met the inclusion criteria. 20 lesions were ultimately diagnosed as benign, and
      40 as malignant. With respect to the diagnosis of malignancy, sensitivity was
      92.5 % (37/40) with B-mode and unenhanced conventional colour/power Doppler US
      ultrasound, 97.5 % (39/40) with contrast-enhanced colour/ power Doppler
      ultrasound, and 100 % with CT; the corresponding specificities were 65 % (13/20),
      85 % (17/20) and 80 % (16/20). 4 of 7 false positive, and 2 of 3 false negative
      results in the unenhanced technique were diagnosed correctly with contrast
      enhanced Doppler ultrasound. CONCLUSION: Compared to conventional ultrasound,
      contrast-enhanced Doppler ultrasound improved the diagnostic accuracy in 10 % of
      the cases. Its accuracy in our study was equal to that of CT.

PMID- 12226763
TI  - [Endobronchial ultrasound for local tumour and lymph node staging in patients
      with centrally growing lung cancer].
AB  - AIM: Lung cancer is a common disease and exact staging is of extreme importance
      in order to plan therapy. A frequent problem in assessing the extent of tumour
      spread is the question of infiltration versus compression of central airways by
      central tumours and a correct lymph node staging. Chest CT as the general imaging
      procedure of choice is often not helpful with these questions. Endobronchial
      ultrasound (EBUS) has been available for several years, and we were interested to
      find out if the addition of EBUS to regular bronchoscopy can help to
      differentiate between airway infiltration and external compression and improves
      the yield of transbronchial needle aspiration (TBNA). METHOD: Patients with
      central tumour growth and enlarged lymph nodes were examined with EBUS and CT,
      classified according to local tumour invasion, and a needle biopsy of the lymph
      nodes was performed after EBUS detection. RESULTS: 50 patients were examined and
      subsequently operated. Relative to the local T-staging EBUS resulted in a
      sensitivity of 89 % and a specificity of 100 %. The results were highly improved
      statistically compared to the CT results (sensitivity 25 %, specificity 80 %).
      With EBUS-guided TBNA the results of correct N-staging could be improved to 86 %.
      CONCLUSION: Our study suggests that EBUS, if performed by experienced
      endoscopists for the detection of airway wall infiltration or compression is
      highly accurate and superior to chest CT in assessing potential airway
      infiltration by a malignant tumour. Furthermore, the results of the lymph node
      staging could be improved through the additional use of EBUS. It is easily
      performed within the context of a standard bronchoscopy and may spare many
      patients unnecessary surgical biopsies.

PMID- 12226764
TI  - [Sonographic measurement of endometrium thickness as a predictive value for
      pregnancy through IVF].
AB  - AIM: This prospective study was performed to evaluate the predictive value of
      endometrium thickness in patients undergoing IVF-ET. METHOD: Measurements of
      endometrium thickness as well as pattern assessments were performed in 936 cycles
      (722 patients) on the day of administering human chronic gonadotropin (HCG).
      RESULTS: The overall pregnancy rate was 31.1 % (291/936). The age of non pregnant
      patient was significantly higher (p < 0.029). There was a significant influence
      of oestradiol (p < 0.029), number of transferred embryos (p < 0.004), and embryo
      quality (p < 0.002) on the pregnancy rate. Overall, the mean (+/- SD) endometrium
      thickness was 11.16 mm (+/- 2.13). The mean (+/- SD) endometrium thickness of
      pregnant patients was 11.25 mm (+/- 2.19). The mean (+/- SD) endometrium
      thickness of non-pregnant patients was 11.12 mm (+/- 2.10). A stepwise logistic
      regression analysis showed no statistically significant correlation between
      endometrium thickness and pregnancy rate (p < 0.23). CONCLUSION: Sonographic
      measurement of endometrium thickness on the day of human chorionic treatment with
      gonadotropin is not useful in predicting IVF outcome.

PMID- 12226765
TI  - [Retrograde flow in the left internal jugular vein caused by compression of the
      left brachiocephalic vein while supine during moderate tidal volume ventilation:
      case report, evaluation by colour coded duplex sonography and review of
      literature].
AB  - This report describes a 67-year-old healthy woman with retrograde flow in the
      left jugular vein in the supine position during moderate tidal ventilation
      detected by colour coded duplexsonography. In the upright position, an
      alternating flow could be found with antegrade direction during inspiration and
      retrograde flow during expiration. CT scan showed no abnormality in the
      mediastinum. CT-angiography in full inspiration demonstrated a normal contrast
      enhanced left brachiocephalic vein. This finding suggests respiration-dependent
      compression of the left brachiocephalic vein between the aortic arch and the
      sternum in the supine position. The clinical relevance for patients with morning
      headaches is discussed. In cases of this phenomenon it is not advisable to use
      veins of the left arm for contrast media injection in CT- or MR-angiography.

PMID- 12226766
TI  - [Sonographic detection of a "VIPoma" in a small child with intractable
      gastroenteritis].
AB  - As case report we describe a rare cause of intractable "gastroenteritis" detected
      by ultrasonography. The 14 months-old boy was admitted to hospital because of
      intensive dehydration due to massive vomiting and diarrhoea. A salmonella
      enteritis with intractable hyponatraemia and hypokalaemia was thought to be the
      cause. After a dramatic relapse during oral treatment measures, further extensive
      laboratory tests finally disclosed an elevated serum level of vasoactive
      intestinal polypeptide ("VIP"). The VIP secreting tumor ("VIPoma") was detected
      ultrasonographically in a retroperitoneal localization mediocaudally of the right
      kidney. Diffuse distinct calcifications and an increased perfusion could be
      demonstrated. Intraspinal tumour spread was excluded by magnetic resonance
      imaging. After complete surgical removal of the tumour the clinical
      symptomatology normalized promptly and permanently. A VIP-excreting
      ganglioneuroblastoma with low grade growth fraction ("VIPoma") was diagnosed
      histologically. Common gastroenteritis in childhood represents no indication for
      ultrasound. In cases of unclear and therapy-resistant symptomatology, however,
      diagnostic work-up should include ultrasonography to search for retroperitoneal
      or pancreatic VIP-excreting tumours.

PMID- 12226767
TI  - [Didactic training of ultrasound instructors].

PMID- 12226768
TI  - [Guidelines for the diagnostics of deep pelvic/lower limb vein thrombosis].
AB  - As a result of availability and failing invasiveness the technique of compression
      sonography led to a change in the indication of thrombosis examination - from the
      proof of thrombosis shown by phlebography to exclusion of thrombosis by
      ultrasound. Compression sonography showed the same sensitivity and specificity as
      phlebography for proximal limb thrombosis and reaches high safety due to actual
      treatment studies in the diagnosis of deep vein thrombosis. For the distal limb
      the compression sonography has provided > 90 % specificity, with an examinator
      dependent sensitivity of 50 to 95 %, and hence examination of the distal limb
      must be recommended. These guidelines for the diagnosis of deep vein thrombosis
      are recommendations by the Section of Vascular Ultrasound of DEGUM for
      examination technique and documentation. It also contains an algorithm of
      diagnosis for thrombosis as a result of the actual treatment studies.

PMID- 12226770
TI  - [Disc replacement with the SB Charite endoposthesis - experience, preliminary
      results and comments after 35 prospectively performed operations].
AB  - Aim of this prospective study was an investigation concerning the indication for
      the implantation of an artificial disc endoprosthesis and the rating of this
      operation. METHOD: 35 patients with 11 bi- and 24 monosegmental implanted disc
      endoprosthesis were observed over an average follow-up of 14.7 months.
      Indications for the operation were: unsuccessful, orthopedic conservative
      treatment > 6 months, segmental pain, age < 45 years, evidence of a radiologic
      (MRI) demonstrable mono- or bisegmental disc degeneration with or without disc
      prolabation, exclusion of psychogenic disease and positive preoperative,
      diagnostic measures. RESULTS: The average stay in the hospital was 16.8 days
      (preoperative: 4.3 days), the average operation time 85.5 minutes, the average
      blood loss was 125 ccm. 23 patients were operated in L 5 / S 1, 20 in L 4 / 5 and
      2 in L 3 / 4. NSAR was given in 33 patients preoperatively, opiates in 2 further
      patients, postoperatively NSAR was necessary in 5 patients, opiates in 2
      patients. The preoperative angle of lordosis (L 1 - S 1, n = 25) was changed from
      35.6 degrees to 42.6 degrees (20,2 %), the segmental angle from 19 degrees to 30
      degrees (57.5 %). CONCLUSION: The implantation of the artificial disc was
      followed by a good pain relief in patients suffering from a mono- or bisegmental
      disc degeneration. In patients with a facett joint arthrosis and elderly patients
      > 45 years this method cannot be used, the indication in patients with failed
      back surgery syndrome cannot be estimated yet. Improvements of the
      instrumentation and the discussion in the case of revisional operations are
      mandatory.

PMID- 12226771
TI  - [Long-term results of quality of life in patients with idiopathic scoliosis after
      Harrington instrumentation and their relevance for expert evidence].
AB  - AIM: The expert evidence of operated patients with idiopathic scoliosis is
      determined by functional and pulmonary restriction. The degree of deformity and
      the extent of fusion is crucial for grading disability. In a retrospective study
      on the quality of life (SF-36) and low back pain (Roland-Morris Score) of 82
      patients (22 - 40 years) with idiopathic scoliosis treated with Harrington
      instrumentation the grading was registered. METHOD: An average of 16.7 years
      after the surgery, these data were correlated with the type and size of curve and
      to the extension of fusion. RESULTS: Compared to the age-matched healthy
      population, there was no significant difference in the physical SF-36 scale (P =
      0.98). Surgically treated patients showed significantly lower scores than at
      baseline in the psychological SF-36 scale (P = 0.005). Sixty-five (79.3 %) of the
      eighty-two patients reported no or occasional back pain in the Roland Index. Five
      patients (6.1 %) complained of chronic back pain. 33 patients (40 %) were legally
      defined in their rate of disability as severely handicapped patients. The grading
      disability was associated with the physical SF-36 scale (P < 0.001) and the low
      back pain (P = 0.02). A significant correlation between the grading disability
      and the extent of fusion (P = 0.53) or the size of curve (p = 0.4) could not be
      proven. CONCLUSION: Despite good long-term outcomes, 40 % of operated treated
      patients with idiopathic scoliosis were legally defined as severely handicapped
      persons. The additional measurements of quality of life and low-back pain can
      improve legal assessment in orthopaedics.

PMID- 12226772
TI  - [A systemic review of the value of physical therapy in whiplash neck injury].
AB  - AIM: A systematic review is performed to evaluate the clinical effects of initial
      immobilisation by a neck collar and physiotherapy in whiplash neck injury.
      METHOD: A computer aided Medline research (1985 - 2002) of randomised clinical
      trials concerning both rehabilitation concepts was conducted. A rating system was
      used to assess the methodological score of each study. Their results were
      analysed and a final statement for evidence according to three main parameters
      (neck pain, range of motion, and patients comfort) was postulated. RESULTS: Eight
      randomised clinical trials were identified. Six studies were determined as high
      quality trials. For the neck, back immobilisation do not appear to improve the
      patients' conditions sufficiently. In comparison, for physiotherapy there is
      strong benefit for pain, range of motion and patients' comfort in comparison to
      no treatment and a soft collar. CONCLUSION: Principally, am early active
      rehabilitation with physiotherapy without initial immobilisation is highly
      recommended in whiplash neck injury.

PMID- 12226773
TI  - [The Efficacy of homeopathy in the treatment of chronic low back pain compared to
      standardized physiotherapy].
AB  - AIM: The aim of this pilot project was to evaluate the efficacy of treatment of
      chronic low back pain during two months either by homeopathy or by standardised
      physiotherapy. METHOD: 43 patients suffering from chronic low back pain were
      included in this controlled, randomised prospective study. They were divided in
      two treatment groups: homeopathy and standardised physiotherapy. Based on the
      initial and final clinical investigations, the Oswestry questionnaire and the
      visual analogue scale, that were assessed at the beginning, at the end and 18.5
      months after therapy, the results were statistically evaluated. A further
      questionnaire documented the acceptance of treatment. RESULTS: A comparison of
      the groups from the beginning to the end of treatment reveals a significant
      decrease of the Oswestry score in patients treated by homeopathy. This tendency
      could not be confirmed 18.5 months later. Homeopathy was well accepted by most of
      the patients. CONCLUSIONS: Based on these results, nothing can be said against
      attempting treatment of chronic low back pain by means of homeopathy. Further
      research is recommended to confirm the results of our investigation, using a
      larger number of patients, a third treatment group, homeopathy double blinded.

PMID- 12226774
TI  - [Rare differential diagnosis of disk prolapse with foot-lifting pareses:
      Spontaneous intramedullary hemorrhage].
AB  - We report on a case of spontaneous intramedullary hemorrhage initially
      misdiagnosed as a lumbar nucleus pulposus prolapse due to the clinical appearance
      and findings on CT-scan.

PMID- 12226775
TI  - [Is lumbar disk disease an occupational disease? Scientific background,
      radiological findings, and medical legal interpretations].
AB  - AIM: It should be cleared whether or not the interpretation of lumbar disk
      disease as an occupational disease is justifiable. Which disc changes follow
      whole-body vibration and can they be distinguished from those which occur
      constitutionally while aging? METHOD: Orthopedic meta-analysis of epidemiological
      and occupational studies concerning the influence of whole- body vibration.
      RESULTS: Reliable studies are rare. Severe methodological problems limit the
      interpretation of difficult relationships. The role of age when working
      influences begin as well as the stress and behaviour of exposed persons away from
      the work-place before and while working with whole-body vibration is not known.
      There is no study which could be called exact according orthopedic criteria. It
      is therefore not evident that whole-body vibration causes lumbar disc disease.
      CONCLUSIONS: After whole-body vibration similar to long term heavy lifting an
      earlier beginning of disk degeneration in X-ray-studies can be observed. This
      leads to prevalence differences, which diminish with increasing age. Deviation to
      the left of the prevalence curve lasts for five to ten years. Whole-body
      vibration leads to a topographic modification of disk degeneration of the lumbar
      spine. After long duration exposition an increased amount of spondylotic changes
      at the thoracolumbar junction and the middle half of lumbar spine can be observed
      (up to the upper plate of the fourth vertebral body). This can be explained by
      biomechanic means: whole-body vibration caused by tractor driving and similar
      long-term exposures leads to traction of the disks of the lower thoracic spine
      and the upper and middle parts of lumbar spine.

PMID- 12226776
TI  - [Occupational diseases of the spine].
AB  - Since 1993 occupational influences of the spine are included into the German
      workman's compensation law (Berufskrankheitenverordnung). Because it is difficult
      to differentiate degenerative from occupational disc diseases only 3 % of the
      proposals have been accepted in the last years. Unfortunately most of the
      epidemiologic studies only consider morphologic changes of the spine but not
      discogenic diseases. More efforts have to be made to prevent spine diseases in
      the working place by exercises and back training. Our results of medical opinions
      in 256 cases of occupational spine diseases are presented and analysed.

PMID- 12226777
TI  - [Clinical and radiological short- and mid-term results of triple pelvic osteotomy
      according to Tonnis in adolescents and adults].
AB  - AIM: We report our clinical and radiological results after triple pelvic
      osteotomy according to Tonnis and accompanying femoral osteotomies in selected
      cases. METHOD: 48 patients were evaluated in a retrospective study with an
      average follow-up to 2 years and 9 months. RESULTS: In 68 % of our patients
      excellent to good results in the Harris Hip Score were achieved. We could
      significantly decrease pain awareness. The CE angle improved significantly from
      10.6 degrees to 32.2 degrees and the acetabular angle of the weight-bearing zone
      according to Bombelli from 20.8 degrees to 3.8 degrees at the last follow-up. The
      VCA angle according to Lequesne and de Seze improved from 18.6 degrees to 33.5
      degrees. Non-union of the ischial or the pubic bone developed in 7 cases as a
      relevant complication. CONCLUSION: On the basis of our results and the
      literature, the triple pelvic osteotomy according to Tonnis can be recommended
      for the treatment of acetabular dysplasia in adolescents and adults.

PMID- 12226778
TI  - [Changes of biomechanical parameters in dysplasia of the hip by total hip
      replacement].
AB  - AIM: Dysplastic hips or dislocated hips lead to loss of muscle strength
      claudication, and finally to coxarthrosis. This study analytically compares the
      hip joint forces in normal, dysplastic hips and hips after implantation of a hip
      prosthesis for several positions. METHOD: The results of 173 total hip
      replacements in 153 cases of either severe congenital dysplasia or dislocation
      were analyzed. A 2 dimensional mathematical model of the hip was developed to
      evaluate the effects of surgically achievable mechanical alterations such as
      acetabular placement, femoral shaft-prosthetic neck angle, and neck length of the
      femoral prosthesis. RESULTS: 63 % of the hip prosthesis were implanted on the
      right, 72 % on the left. Before implantation, the femoral shaft-prosthetic neck
      angle in mean was 146 degrees +/- 10 degrees, after implantation it was 135
      degrees. The hip centre was displaced on in average 10 mm distally.
      Postoperatively hip joint force was increased 21 %. CONCLUSION: Minimum joint
      contact forces occurred when the femoral shaft prosthetic neck angles were small.
      The loads on the hip were lowered significantly by placing the centre of the
      acetabulum as far inferiorly and medially as possible. Another important finding
      is that displacement of the hip centre distally has a great effect on muscle
      performance and hip joint force.

PMID- 12226780
TI  - [Electrical fields in the knee joint induced by external magnetic fields: results
      of an experimental study].
AB  - AIM: Magnetic fields are used in the treatment of osteoarthritis. So far the
      efficiency has not been scientifically proven. The comparability of induced
      electrical fields with those produced endogenously within the cartilage tissue is
      unknown. METHOD: The study was performed on a knee joint model which was exposed
      to magnetic fields (2mT and 4.9 mT, 50 Hz). The measurements were performed using
      small spherical electrodes within the knee joint located at positions defined by
      three cartesian coordinates. The electrical potentials were amplified 100-fold
      and plotted on an oscilloscope. The results were checked by post-mortem
      examinations on a human knee joint. RESULTS: In relation to the magnetic flux
      density and the steric orientation of the electrodes, we found electric field
      strengths between 60 and 410 micro V/cm. When performing the procedure on the
      human knee joint, field strengths of up to 400 micro V/cm were measured.
      CONCLUSIONS: Electrical fields in the knee joint which are induced by external
      magnetic fields can be verified. When compared with the endogenous electrical
      potentials, the measured values were about 30 times smaller. Given these results,
      we can make no conclusions about therapeutic efficiency.

PMID- 12226779
TI  - [Medical-legal aspects in fractured ceramic liners after implantation of a hip
      endoprosthesis].
AB  - We report the case of a male patient after implantation of a thrust plate
      endoprosthesis to discuss reliable questions concerning the insurance and
      liability fields. The indication for implantation of this type of endoprosthesis
      should be decided critically. To prevent an early implant failure, both
      articulating ceramic partners - the liner and the femoral head - should be
      exchanged in any case of doubt during a hip revision surgery. In case of an
      implant failure, a surface analysis of the broken fragments can show signs of
      material insufficiencies. A detailed preoperative consent of the patient combined
      with an exact documentation is necessary to prevent potential medical claims by
      the patient, and also increases the compliance and reduces the costs for the
      health system.

PMID- 12226781
TI  - [Diagnosis and differential diagnosis of extraskeletal, para-articular chondroma
      of the knee].
AB  - AIM: Extraskeletal chondromas in the region of the knee joint are very rare
      tumors which may cause diagnostic problems and have concomitant therapeutic
      consequences. METHOD: In a case report we present the clinical, radiological and
      histological features of an a extraskeletal chondroma. RESULTS: A 47-year-old
      female patient presented with an infrapatellar, painless tumor of the knee joint.
      The clinical features were unspecific. On plain X-ray images, calcifications were
      visabled within Hoffa's fat pad. An important preoperative imaging procedure was
      MRI, which showed a well defined mass of 2.5 cm in diameter with a hyperintense
      signal on fat suppressed images. Subsequent operative therapy involved marginal
      resection of the tumor. CONCLUSION: The differentiation of this entity especially
      from myxoid chondrosacroma and synovial chondroamatosis was crucial with respect
      to an adequate therapy. Further differential diagnoses included heterotopic
      ossifications, synovial sarcoma, mesenchymoma and soft-tissue osteosarcoma.

PMID- 12226782
TI  - [Shock wave therapy for recalcitrant plantar fasciitis with heel spur: a
      prospective randomized placebo-controlled double-blind study].
AB  - AIM: Efficacy of low-energy shock wave therapy for recalcitrant plantar
      fasciitis. METHOD: 32 patients were randomly assigned into real and placebo ESWT
      groups, treatment comprised 1000 impulses of 0,08 mJ/mm 2 at 14 kV (OssaTron OSA
      120, HMT AG, Switzerland) in 12 cases repeated after six weeks or placebo (energy
      absorbing foil). Follow-up evaluation (19, 32 and 48 wks.) included specific
      questionnaire, clinical-functional examination and measurement of plantar
      pressure while walking (Emed AT-4. pedograph, Novel GmbH, Munich). Examiner and
      patients were blinded. RESULTS: 88 % of the treatment group were pain free or had
      good results. None of the placebo group were pain free, 33.3 % had good results
      (Roles and Maudsley Score). The treatment group showed significantly better
      outcome for morning and resting pain, pressure stamp-tolerance and walking
      ability. Pedography did not show a clear correlation between pain relief and load
      pattern. CONCLUSION: The results of this study corroborate the value of ESWT for
      recalcitrant plantar fascitis. As a non invasive technique with low side effects,
      it can complement the row of conservative treatments.

PMID- 12226783
TI  - [Infections of the musculoskeletal system with chronic polyarthritis during a
      combination therapy with Methotrexate and Leflunomide].
AB  - AIM: The long-term results of rheumatoid arthritis are unsatisfactory despite the
      mono or combination therapy of conventional "disease-modifying antirheumatic
      drugs". Therefore in the recent past the administration of a combination of
      Methotrexate with Leflunomide takes place more frequently. To what extent the
      perioperative infection rate is influenced by the individual immune-modulating
      drugs, is still disputed and should quantified on the basis the rheumatism
      orthopaedic patient collective of an orthopaedic university clinic. METHOD: The
      clinical progresses of patients after operative treatment in the orthopaedic
      hospital, since introduction of the Leflunomide, were evaluated with regard to
      perioperative infection. RESULTS: Of 16 patients, who were observed during a
      period of 1,5 years under a combination therapy by MTX/Leflunomide, three
      exhibited a heavy infection of the musculoskeletal system. CONCLUSION: The
      combination of the two above mentioned drugs affects different pathophysiological
      processes. Synergistic effects in therapy but also with regard to side effects
      must be expected. First available reports on this combination therapy do not
      refer to a increased infection/risk. The observation of three serious infections
      under the combination MTX/Leflunomide prompted us to call attention to this risk.
      In particular with infection-susceptible bone-surgical operations such a
      combination of immune-modulating medicines should be employed with caution. The
      recent literature is discussed.

PMID- 12226784
TI  - [Gait disorders - assessment and rehabilitation supported by movement analysis].
AB  - AIM: The present paper validates the use of two-dimensional pelvis and thorax
      translation data for the assessment of gait disturbances and evaluates the
      effects of a real-time visual feedback system based on thoracic spine kinematics
      for gait rehabilitation. METHODS: To validate the use of two-dimensional gait
      kinematics, vertical and horizontal displacements of pelvis (S1) and thorax (T12)
      markers of the twelve healthy individuals (25.9 +/- 2.7 years) were recorded
      during two gait perturbations: a brace constraining the knee to 30 degrees of
      flexure and a shoe lift of 3 cm. To investigate the effects of verbal
      instructions and additional real-time visual feedback on vertical and medial
      lateral pelvis and trunk movements, gait kinematics were recorded during three
      randomized trials (verbal instruction, real-time visual kinematic feedback, free
      walking). RESULTS: Gait deviations did result in significant (p < 0.05) increases
      of horizontal and vertical trunk pelvis movements. Significant (p < 0.05)
      reductions in oscillation amplitudes were noted when verbal cues and visual
      information were received. However, the major decrease occurred during real-time
      visual feedback. CONCLUSION: Asymmetric limping, similar to gait disorders of
      individuals with hip pathologies, could be detected and described by two
      dimensional thorax and pelvis translation data. It could be speculated that gait
      disorders may be addressed by real-time kinematic feedback training.

PMID- 12226785
TI  - Peripheral arterial disease (PAD): secondary prevention.
AB  - SUMMARY: The prevalence of PAD rises as the population becomes increasingly
      older. At present, about 4.5 million citizens in Germany are estimated to be
      affected. In only one third of the patients intermittent claudication is found as
      a classical PAD marker. The course is thus predominantly asymptomatic.
      Consequently, careful evaluation of patients, including case history and pulse
      status as well as detailed recording of risk factors of atherosclerosis (chiefly
      smoking and diabetes mellitus), are important. When noninvasive methods of
      investigation is taken into account, the prevalence rises two- to three-fold.
      Duplex sonography with measurement of the ankle-brachial index (ABI) is a method
      which has so far not been used widely although it is highly accurate. Life
      expectancy of patients with PAD is shortened by about ten years. The prognosis is
      determined by the natural course of the disease in only a few patients (ischemia
      syndrome and/or ABI < 0.4). Patients are at much greater risk for cardiovascular
      and cerebrovascular incidents than of a systemic disease. Mortality is raised up
      to six fold by concomitant coronary heart disease. Therapy should therefore not
      only be designed to treat the peripheral, as well as the atherosclerosis. Like
      walk training under supervision, no smoking, optimal glycemic control in diabetic
      patients and restoration of the lipid status to normal are treatment measures
      that have proved to be effective. As for pharmacotherapy, the efficacy of
      thrombocyte aggregation inhibitors is regarded as proved, whereas many drugs
      targeting symptoms have yielded disappointing results in patients with
      intermittent claudication.

PMID- 12226786
TI  - [Rheumatology on the move].

PMID- 12226787
TI  - [Thrombotic thrombocytopenic purpura - a rare cause of thrombocytopenia in
      systemic lupus erythematosus].
AB  - HISTORY AND ADMISSION FINDINGS: An 18-year old woman with a systemic lupus
      erythematosus was referred to our hospital with anaemia, thrombocytopenia and
      neurological symptoms. Skin haemorrhages had occurred some weeks before. The
      patient also noticed cardiac palpitations. After the primary care doctor had
      increased the dosage of prednisolone from 7.5 mg per day to 20 mg per day the
      symptoms didn't substantially change and that the patient was referred to
      hospital. An acute lupus flare was assumed. INVESTIGATIONS: Laboratory
      examinations showed a Coombs-negative haemolytic anaemia with schistocytes. Von
      Willebrand factor(vWF)-cleaving protease was decreased. The presence of an
      inhibitor of the enzyme was proved. Further test results as anti-ds-DNA, anti-Sm,
      C 3, ESR, CRP were normal. C 4 was slightly decreased. Cerebral MRI, cerebral
      SPECT and Duplex sonography of the extracranial arteries didn't show any
      pathologic findings. The performed MRI of the heart revealed signs of myocardial
      damage. DIAGNOSIS, TREATMENT AND COURSE: As cause of the recent symptoms a
      thrombotic-thrombocytopenic purpura (TTP) was diagnosed. This obviously was due
      to an auto-antibody against the vWF-cleaving protease. After intensive
      immunosuppressive therapy with prednisolone and cyclosporin the clinical and
      laboratory findings normalised. An acute therapy with fresh frozen plasma and
      plasmapheresis was not necessary, as the symptoms were moderate. Because of the
      transient cerebral deficits for a short time we administered a low dose of
      aspirin. The MRI signs of myocardial affection didn't change after 3 months of
      immunosuppressive treatment so that we started an ACE inhibitor treatment.
      CONCLUSION: Thrombocytopenia in systemic lupus erythematosus demands an
      individual differential diagnosis. Rare causes as TTP have to be excluded. This
      disorder has to be diagnosed quickly and the adequate therapy has to be started
      early.

PMID- 12226788
TI  - [Chronic reactive arthritis associated with Calmette-Guerin bacillus].
AB  - HISTORY AND ADMISSION FINDINGS: After successful transurethral resection of a
      superficial bladder cancer a 59-year old patient was treated with intravesical
      instillation of bacillus Calmette-Guerin (BCG) six times to prevent tumor
      recurrence. Four weeks later the patient was admitted to our department
      presenting with symmetrical polyarthritis accompanied by pain and stiffness and
      conjunctivitis. INVESTIGATIONS: Laboratory tests showed evidence of severe
      inflammation, but cultures of blood, urine and joint fluid specimens were
      negative, as were tests for autoantibodies and serologic tests for organisms
      known to cause reactive arthritis. DIAGNOSIS: In this patient, the history,
      admission findings and laboratory tests led to the diagnosis of BCG-immunotherapy
      associated reactive arthritis. TREATMENT AND COURSE: Nonsteroidal
      antiinflammatory therapy was ineffective but glucocorticoid therapy resulted in a
      partial response. With additional administration of the antituberculosis agent
      isoniazid for 3 months, all symptoms resolved. CONCLUSION: Reactive arthritis can
      be induced by BCG-immunotherapy. The treatment with nonsteroidal antiinflammatory
      drugs and steroids is sufficient in many patients. In case of unresponsiveness,
      however, antituberculosis therapy is indicated.

PMID- 12226789
TI  - [Diagnosis and antibiotic treatment of reactive arthritis].

PMID- 12226790
TI  - [Treatment of defects of joint cartilage].

PMID- 12226791
TI  - [How long should cyclophosphamide therapy of Wegener's granulomatosis continue?].

PMID- 12226792
TI  - [Corticosteroid saving-up in giant cell arteritis?].

PMID- 12226793
TI  - Elevated minisatellite mutation rate in the post-chernobyl families from ukraine.
AB  - Germline mutation at eight human minisatellite loci has been studied among
      families from rural areas of the Kiev and Zhitomir regions of Ukraine, which were
      heavily contaminated by radionuclides after the Chernobyl accident. The control
      and exposed groups were composed of families containing children conceived before
      and after the Chernobyl accident, respectively. The groups were matched by
      ethnicity, maternal age, parental occupation, and smoking habits, and they
      differed only slightly by paternal age. A statistically significant 1.6-fold
      increase in mutation rate was found in the germline of exposed fathers, whereas
      the maternal germline mutation rate in the exposed families was not elevated.
      These data, together with the results of our previous analysis of the exposed
      families from Belarus, suggest that the elevated minisatellite mutation rate can
      be attributed to post-Chernobyl radioactive exposure. The mechanisms of mutation
      induction at human minisatellite loci are discussed.

PMID- 12226797
TI  - Resistance mechanisms.
AB  - During the past decade, there has been extensive investigation of bacterial
      resistance mechanisms. The interplay of genetic and antibiotic factors on
      antibiotic resistance are multiple and complex. Antibiotic resistance is the
      clinical expression of these factors. This article reviews the most studied and
      understood mechanisms of resistance in bacterial species in which resistance
      problems have clinical significance. Besides plasmid mediated resistance some
      resistance problems among respiratory pathogens are clonal resistance. The
      precise cause of this actual genetic event causing bacterial mutation
      recombination and selection is not always clear. Although resistance mechanisms
      may be identical within an antibiotic class, expression of resistance often
      varies among antibiotics of the same class.

PMID- 12226795
TI  - Gene expression phenotype in heterozygous carriers of ataxia telangiectasia.
AB  - The defining characteristic of recessive diseases is the absence of a phenotype
      in the heterozygous carriers. Nonetheless, subtle manifestations may be
      detectable by new methods, such as expression profiling. Ataxia telangiectasia
      (AT) is a typical recessive disease, and individual carriers cannot be reliably
      identified. As a group, however, carriers of an AT disease allele have been
      reported to have a phenotype that distinguishes them from normal control
      individuals: increased radiosensitivity and risk of cancer. We show here that the
      phenotype is also detectable, in lymphoblastoid cells from AT carriers, as
      changes in expression level of many genes. The differences are manifested both in
      baseline expression levels and in response to ionizing radiation. Our findings
      show that carriers of a recessive disease may have an "expression phenotype." In
      the particular case of AT, this suggests a new approach to the identification of
      carriers and enhances understanding of their increased cancer risk. More
      generally, we demonstrate that genomic technologies offer the opportunity to
      identify and study unaffected carriers, who are hundreds of times more common
      than affected patients.

PMID- 12226794
TI  - Genetic sophistication of human complement components C4A and C4B and RP-C4-CYP21
      TNX (RCCX) modules in the major histocompatibility complex.
AB  - Human populations are endowed with a sophisticated genetic diversity of
      complement C4 and its flanking genes RP, CYP21, and TNX in the RCCX modules of
      the major histocompatibility complex class III region. We applied definitive
      techniques to elucidate (a) the complement C4 polymorphisms in gene sizes, gene
      numbers, and protein isotypes and (b) their gene orders. Several intriguing
      features are unraveled, including (1) a trimodular RCCX haplotype with three long
      C4 genes expressing C4A protein only, (2) two trimodular haplotypes with two long
      (L) and one short (S) C4 genes organized in LSL configurations, (3) a
      quadrimodular haplotype with four C4 genes organized in a SLSL configuration, and
      (4) another quadrimodular structure, with four long C4 genes (LLLL), that has the
      human leukocyte antigen haplotype that is identical to ancestral haplotype 7.2 in
      the Japanese population. Long-range PCR and PshAI-RFLP analyses conclusively
      revealed that the short genes from the LSL and SLSL haplotypes are C4A. In four
      informative families, an astonishingly complex pattern of genetic diversity for
      RCCX haplotypes with one, two, three and four C4 genes is demonstrated; each C4
      gene may be long or short, encoding a C4A or C4B protein. Such diversity may be
      related to different intrinsic strengths among humans to defend against
      infections and susceptibilities to autoimmune diseases.

PMID- 12226798
TI  - Extended-spectrum beta-lactamases.
AB  - Extended-spectrum beta-lactamases (ESBLs) were discovered in Europe in the early
      1980s after widespread use of broad-spectrum antibiotics. They are largely
      derivatives of 3 progenitor beta-lactamases that confer resistance to ampicillin
      in gram-negative bacteria and are now carried on plasmids. Substitutions at the
      active enzyme site of these progenitor enzymes at single or multiple amino sites
      have resulted in altered substrate affinities for ESBLs. Depending on the
      location of the substitution, susceptibility to broad-spectrum antibiotics is
      variably diminished. ESBLs are most commonly found in Klebsiella species and
      Escherichia coli, but also in other bacteria including Pseudomonas, Salmonella,
      Proteus, and Enterobacter species. The discovery of ESBLs in hospital and nursing
      home outbreaks and their ability to be transferred to other bacterial species
      makes management and treatment of ESBLs of great medical concern.This article
      provides a review of ESBLs and their impact on patient care.

PMID- 12226799
TI  - Antibiotic resistance of oral anaerobic bacteria and their effect on the
      management of upper respiratory tract and head and neck infections.
AB  - Anaerobes of oral origin are common in chronic upper respiratory tract and other
      head and neck infections. Anaerobes are the predominant components of the normal
      human oropharyngeal flora, and are therefore a common cause of bacterial
      infections of the upper respiratory tract that are of endogenous origin. These
      bacteria can be isolated in chronic otitis media, sinusitis, and tonsillitis, and
      their complications. Anaerobes also predominate in deep oral and neck infections
      and abscesses. Their isolation requires appropriate methods of collection,
      transportation, and cultivation of specimens. In addition to their active
      pathogenic role in these infections, many anaerobes express an indirect effect
      through their ability to produce the enzyme beta-lactamase. This enables these
      organisms to shield non-beta-lactamase-producing bacteria (BLPB) from
      penicillins. Inadequate therapy against BLPB may lead to clinical failures.
      Treatment of anaerobic infection is complicated by their slow growth, their
      polymicrobial nature, and the growing resistance of anaerobic bacteria to
      antimicrobials. Antimicrobial therapy is often the only form of therapy needed,
      whereas in other instances it is an important adjunct to a surgical approach.
      Because anaerobes generally are isolated mixed with aerobic organisms, therapy
      should provide for adequate coverage of both types of pathogens.

PMID- 12226800
TI  - Clinical relevance of penicillin-resistant Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is the most important respiratory tract pathogen in
      otitis, sinusitis, bronchitis, and community-acquired pneumonia. Over the past
      decades, there has been an increase in minimum inhibitory concentrations (MICs)
      to penicillin. Decreased susceptibility to penicillin is not the same as
      penicillin resistance. Decreased susceptibility to penicillin has occurred
      worldwide from dissemination of several resistant pneumococcal clones, and, to a
      lesser extent, from excessive use of ciprofloxacin, macrolides, and trimethoprim
      sulfamethoxazole (TMP-SMX). Currently, penicillin resistance is defined by using
      a breakpoint of 2 microg/mL or more. Intermediately resistant strains (MIC 1-2
      microg/mL) are also relatively sensitive depending on antibiotic concentration.
      Intermediate antibiotic susceptibility is concentration dependent. Antibiotic
      concentration at various body sites is determined by pharmacokinetic
      considerations. Except for very highly resistant strains, the treatment of
      penicillin-resistant S. pneumoniae causing bacteremia, sinusitis, otitis,
      bronchitis, or community-acquired pneumonia remains penicillin or any beta
      lactam. Only in pneumococcal meningitis caused by penicillin-resistant
      pneumococci does the clinician have to use care in selecting an antipneumococcal
      antibiotic with adequate cerebrospinal fluid penetration and favorable kill
      ratios. Clinicians should be selective in antibiotic selection to minimize
      further decreases in penicillin susceptibility to S. pneumoniae. This is best
      achieved by using low-resistance potential antibiotics oral/intravenous mono
      therapy at the full recommended dose. Therapeutic failure may occur in using
      lower doses at certain body sites. Macro-lides as monotherapy or as part of
      combination therapy should be minimized. Optimal therapy for non-central nervous
      system pneumococcal infection is with a respiratory quinolone (eg, levofloxacin,
      gatifloxacin, moxifloxacin), clindamycin, doxycycline, third-generation
      cephalosporins. For highly resistant pneumococci, levofloxacin, gatifloxacin,
      moxifloxacin, cefepime, meropenem, vancomycin, or linezolid may be used.

PMID- 12226801
TI  - Klebsiella and enterobacter: antibiotic resistance and treatment implications.
AB  - KLEBSIELLA: spp. and Enterobacter spp. are widespread throughout the environment
      and also carried by humans. Both genera are well-recognized community and
      nosocomial pathogens and cause significant infections. They are a common cause of
      respiratory and nonrespiratory infections. Klebsiella spp. is responsible for 1%
      to 5% of all cases of community-acquired pneumonia and between 0% to 23% of those
      acquired in the hospital, and its frequency is greater in alcoholic patients. The
      majority of cases are unilateral in the posterior segment of the right upper
      lobe. Lung abscess can occur after a pneumonic process or secondarily to
      Klebsiella spp. infections and have high rates of morbidity and mortality. K.
      pneumoniae is one of the most common microorganisms responsible for empyema.
      Klebsiella spp. and Enterobacter spp. rank fourth and third, respectively, as
      causes of hospital-acquired pneumonia mainly in patients during the early period
      of mechanical ventilation. Klebsiella spp. are intrinsically resistant to
      penicillins and can acquire resistance to third- and fourth-generation
      cephalosporins owing to the production of plasmid-mediated extended-spectrum beta
      lactamases (ESBLs). These plasmids frequently carry aminoglycoside-modifying
      enzymes. Enterobacter spp. are intrinsically resistant to ampicillin,
      amoxicillin, amoxicillin-clavulanate, first-generation cephalosporins, and
      cefoxitin owing to the production of constitutive AmpC beta-lactamase. The
      derepression of this enzyme is increasingly frequent among clinical isolates and
      confers resistance to third-generation cephalosporins, and ureido- and
      carboxypenicillins; fourth-generation cephalosporins retain reasonable activity
      against depressed strains. Most isolates of Klebsiella spp. and Enterobacter spp.
      are susceptible to fluoroquinolones, trimethoprimsulfamethoxazole,
      aminoglycosides, and carbapenems. In some instances, treatment of severe
      infections caused by these microorganisms may benefit from the combination of
      beta-lactams (or fluoroquinolones) with aminoglycosides. Because of the high risk
      for developing resistance during treatment, all severe infections should be
      carefully watched during therapy.

PMID- 12226802
TI  - Pseudomonas aeruginosa: resistance and therapy.
AB  - Pseudomonas aeruginosa resistance to antimicrobials is an important therapeutic
      consideration. Antibiotic resistance to P. aeruginosa may be chromosomally or
      plasmid mediated. Resistance to P. aeruginosa may also be affected by changes in
      the cellular membrane or intracellular environment. P. aeruginosa is primarily a
      nosocomial organism that most commonly colonizes respiratory secretions and
      urine. The selection of an antipseudomonal antibiotic depends on its inherent in
      vitro activity and its resistance potential. Anti-P. aeruginosa antibiotics with
      a high-resistance potential include gentamicin, tobramycin, ciprofloxacin,
      ceftazidime, and imipenem. Anti-P. aeruginosa antibiotics with a low-resistance
      potential include amikacin, piperacillin, cefoperazone, cefepime, meropenem, and
      polymyxin B.

PMID- 12226803
TI  - Effect of antibiotic pretreatment on resistance.
AB  - The emergence of bacterial resistance to antibiotics limits the efficacy of
      technical developments in the field of infectious diseases. This is particularly
      true for respiratory tract infections, which are by far the main reason for
      antibiotic use in developed countries. Antimicrobial resistance among respiratory
      pathogens involves both gram-positive (primarily Streptococcus pneumoniae) and
      gram-negative (Haemophilus influenzae, Moraxella catarrhalis, and the more rare
      enterobacteriaceae) microorganisms. A number of epidemiologic studies show a
      relationship between antibiotic use and antibiotic resistance, and how antibiotic
      pretreatment can reduce the range of effective drugs for optimal therapy of
      infections in general and of respiratory tract infections in particular. An
      appropriate use of antimicrobials is of crucial importance to limit the emergence
      and spread of bacterial resistance to antibiotics. This can be achieved by
      avoiding usage in nonspecific, probably viral, infections that are unlikely to be
      influenced by antibiotic therapy, and by using narrow-spectrum drugs to minimize
      selective pressure.

PMID- 12226804
TI  - The environment as a significant cofactor for multiply resistant nosocomial
      infections.
AB  - The role of antimicrobial agent control in the war against the development of
      resistance is not the only issue in this conflict. In this article, the role the
      environment plays in the spread of pathogens is discussed.

PMID- 12226805
TI  - Strategies to control antibiotic resistance.
AB  - Antibiotic resistance is becoming a worldwide concern. Antibiotic resistance may
      be caused by sporadic mutations, which are not important unless spread clonally.
      Clonal resistance may disseminate a highly resistant clone to widespread
      geographic areas. The most effective interventions to limit the clonal spread of
      resistant organisms are effective infection control measures. Hospital antibiotic
      formulary restriction is the only control measure with proven effectiveness to
      control resistance related to antibiotic use. Hospital formularies should
      eliminate or restrict antibiotics with a high-resistance potential (eg,
      ceftazidime, ciprofloxacin, and imipenem), and should be replaced with equivalent
      antibiotics with a low-resistance potential (eg, cefe-pime, levofloxacin, and
      meropenem). Such low-resistance-potential antibiotics can either prevent or
      eliminate resistance problems associated with Klebsiella pneumoniae, Enterobacter
      species, or Pseudomonas aeruginosa. High-resistance-potential antibiotics,
      particularly ciprofloxacin and ceftazidime, also may indirectly increase the
      prevalence of highly resistant organisms (eg, methicillin-resistant
      Staphylococcus aureus [MRSA], vancomycin-resistant enterococci [VRE]). Vancomycin
      use should be restricted, not because it increases enterococcal resistance per
      se, but because it selects out naturally resistant enterococcal strains (eg,
      Enterococcus faecium that are vancomycin resistant). Linezolid does not increase
      the prevalence of VRE. Clinicians in the outpatient setting should also
      preferentially use oral antibiotics with a low-resistance potential (eg,
      clindamycin, metronidazole, doxycycline, minocycline, fluoroquinolones except
      ciprofloxacin, linezolid, and oral cephalosporins) in preference to their high
      resistance-potential counterparts. For antibiotic resistance control
      interventions to be effective, they must be applied simultaneously to all
      antibiotics with activity against the specific resistance pathogen at the
      hospital formulary level. Multiple antibiotic substitutions are usually necessary
      to eradicate resistance problems caused by a particular pathogen. Multiple drugs
      of the same spectrum and low-resistance potential are necessary to eliminate
      resistance problems; single antibiotic substitutions are not effective.

PMID- 12226806
TI  - Histology and histochemistry of heart muscle: toward function with structure in
      mind.

PMID- 12226807
TI  - Natriuretic peptides in relation to the cardiac innervation and conduction
      system.
AB  - During the past two decades, the heart has been known to undergo endocrine
      action, harbouring peptides with hormonal activities. These, termed "atrial
      natriuretic peptide (ANP)," "brain natriuretic peptide (BNP)," and "C-type
      natriuretic peptide (CNP)," are polypeptides mainly produced in the cardiac
      myocardium, where they are released into the circulation, producing profound
      hypotensive effects due to their diuretic, natriuretic, and vascular dilatory
      properties. It is, furthermore, well established that cardiac disorders such as
      congestive heart failure and different forms of cardiomyopathy are combined with
      increased expression of ANP and BNP, leading to elevated levels of these peptides
      in the plasma. Besides the occurrence of natriuretic peptides (NPs) in the
      ordinary myocardium, the presence of ANP in the cardiac conduction system has
      been described. There is also evidence of ANP gene expression in nervous tissue
      such as the nodose ganglion and the superior cervical ganglion of the rat,
      ganglia known to be involved in the neuronal regulation of the heart.
      Furthermore, in the mammalian heart, ANP appears to affect the cardiac autonomic
      nervous system by sympathoinhibitory and vagoexcitatory actions. This article
      provides an overview of the relationship between the cardiac conduction system,
      the cardiac innervation and NPs in the mammalian heart and provides data for the
      concept that ANP is also involved in neuronal cardiac regulation.

PMID- 12226808
TI  - Non-radioactive in situ detection of mRNA in ES cell-derived cardiomyocytes and
      in the developing heart.
AB  - Non-radioactive in situ hybridisation is an excellent method to visualise mRNA
      molecules within their topographical context. Recently we have reported a new non
      radioactive in situ hybridisation procedure on tissue sections that is
      essentially based on the whole mount in situ hybridisation procedure. This method
      is superior in spatial resolution and sensitivity compared to the radioactive in
      situ hybridisation procedure. Generally, low levels of gene expression, such as
      found with the developmental onset of gene expression and in differentiating
      embryonic stem cells, are difficult to detect by in situ hybridisation. Here an
      application of the protocol is presented which is based on tyramide signal
      amplification, which enables the detection of very low abundant mRNAs. The
      significance of this method is two-fold: (1) the molecular phenotype of embryonic
      stem cell-derived cardiomyocytes can be examined at the cellular level with high
      sensitivity, and (2) the number of cells that express the gene of interest can be
      assessed.

PMID- 12226809
TI  - Cell death and differentiation in the development of the endocardial cushion of
      the embryonic heart.
AB  - The transformation of the endocardial cushion into valves and septa is a critical
      step in cardiac morphogenesis as it initiates the development of the four
      chambered heart. This transformation results from a region-specific balance
      between cellular proliferation, apoptosis, and differentiation. The development
      of the form and structure of the endocardial cushion is accompanied by precise
      patterns of abundant cell death having the morphological features of programmed
      cell death (apoptosis), which plays an important role in the elimination of
      redundant cells and in changes of phenotypic composition during histogenesis.
      Apoptosis is an essential process in morphogenesis as it balances mitosis in
      renewing tissues. It is controlled by one or more genetic programs that kill the
      targeted cell. However, the causes, role, and regulation of apoptosis in the
      developing endocardial cushion still remain to be determined. The clarification
      of the role of the apoptosis regulatory genes constitutes a major task in future
      studies of cell death in the developing heart. This new molecular histology of
      heart development awaits further experiments to clarify the interactive
      mechanisms that act to ensure the sculpting of the endocardial cushion into
      valves and septa by determining the size of the cushion cell populations. The
      relation between the expression of different factors and the modifications of the
      cushion region during cardiac development are reviewed. In addition, we review
      and summarize information on molecules identified in our experiments that imply
      the activity of a number of essential genes coinciding with the key steps in
      generating the overall architecture of the heart. We correlate their temporal and
      spatial expression with their proposed roles.

PMID- 12226810
TI  - Myotonic dystrophy protein kinase of the cardiac muscle: evaluation using an
      immunochemical approach.
AB  - Myotonic dystrophy (DM) is an inherited multisystem disorder characterized by the
      presence of a high polymorphic expansion of trinucleotide (CTG) repeat in the 3'
      untranslated region of the DM protein kinase (DMPK) gene. However, the role of
      myotonic dystrophy protein kinase (DMPK) has yet to be elucidated. Studies aimed
      to discover possible physiological targets of DMPK indicated several subcellular
      localization sites, such as neuromuscular junctions, myotendinous junctions, and
      terminal cisternae of the sarcoplasmic reticulum in the skeletal muscle and
      intercalated discs in the cardiac muscle. Here, we extend our previous
      observations on the localization of DMPK at gap junction (GJ) level in the heart,
      taking advantage of the polyclonal peptide-specific anti-DMPK antibodies raised
      against two different domains of the protein. DMPK was detected by
      immunofluorescence at the intercalated disc level by both antibodies. Double
      immunofluorescence staining experiments performed with each anti-DMPK and anti
      connexin43 showed colocalization of the two antigens. Immunoblot analysis of
      partially purified GJs showed co-sedimentation of DMPK and connexin43. We
      conclude that GJs are a genuine localization site of DMPK. Given the known
      regulation exerted by protein kinases on assembly, trafficking, gating, and
      disassembly of connexins, such a localization may be relevant to the functional
      role of connexins. DM is the most common muscular dystrophy in adults, and is
      known by the cardiac involvement that is a common feature in DM patients.
      Localization of DMPK at GJ in relation to DM is also briefly discussed.

PMID- 12226811
TI  - Calibrated histochemistry applied to oxygen supply and demand in hypertrophied
      rat myocardium.
AB  - Oxygen supply and demand of individual cardiomyocytes during the development of
      myocardial hypertrophy is studied using calibrated histochemical methods. An
      oxygen diffusion model is used to calculate the critical extracellular oxygen
      tension (PO(2,crit)) required by cardiomyocytes to prevent hypoxia during
      hypertrophic growth, and determinants of PO(2,crit) are estimated using
      calibrated histochemical methods for succinate dehydrogenase activity,
      cardiomyocyte cross-sectional area, and myoglobin concentration. The model
      calculation demonstrates that it is essential to calibrate the histochemical
      methods, so that absolute values for the relevant parameters are obtained. The
      succinate dehydrogenase activity, which is proportional to the maximum rate of
      oxygen consumption, and the myoglobin concentration hardly change while the
      cardiomyocytes grow. The cross-sectional area of the cardiomyocytes, which
      increases up to threefold in the right ventricular wall due to pulmonary
      hypertension in monocrotaline-treated rats, is the most important determinant of
      PO(2,crit) in this model of myocardial hypertrophy. The relationship between
      oxygen supply and demand at the level of the cardiomyocyte can be investigated
      using paired determinations of spatially integrated succinate dehydrogenase
      activity and capillary density. Hypoxia-inducible factor 1alpha can be
      demonstrated by immunohistochemistry in cardiomyocytes with high PO(2,crit) and
      increased spatially integrated succinate dehydrogenase activity, indicating that
      limited oxygen supply affects gene expression in these cells. We conclude that a
      mismatch of oxygen supply and demand may develop during hypertrophic growth,
      which can play a role in the transition from myocardial hypertrophy to heart
      failure.

PMID- 12226812
TI  - Lipopolysaccharide administration increases acid and alkaline phosphatase
      reactivity in the cardiac muscle.
AB  - The effect of lipopolysaccharide (LPS) administration on the in situ distribution
      of the reaction product of acid phosphatase (AcPase) and alkaline phosphatase
      (AlPase) activity was examined in the rat cardiac muscle using catalytical
      cytochemistry. Tissues of the heart were fixed and then incubated in reaction
      media for detection of AcPase and AlPase reactivity. In normal hearts, reaction
      product of AcPase activity was observed in lysosomes. AlPase reactivity was
      detected at the extracellular surface of the capillary endothelilal cells and in
      their caveolae. Following LPS administration, the number and the size of
      lysosomes possessing AcPase reactivity as well as their electron density
      significantly increased. Furthermore, they tended to form groups consisting of
      three to five lysosomes. Cytochemical reaction 2 and 24 hours after injection was
      similar. One week later, the reaction returned to its normal pattern. As in the
      case with AcPase, the first changes of the distribution of the reaction product
      of AlPase activity were detected 2 hours after injection. The changes included a
      remarkable increase of the number of enzymatically positive capillaries,
      intensified cytochemical reaction in endothelial cells, and an increased number
      of caveolae. Again, no noticeable differences in reactivity were observed 2 and
      24 hours after injection and the reaction returned to normal one week later.
      Collectively, our data indicate that both cardiac AcPase and AlPase are affected
      early after injection of LPS. Although the pattern of cytochemical reaction of
      both phosphatases was restored one week later, it is believed that the altered
      distribution of their reactivity in early periods after LPS administration may be
      a factor contributing to the development of pathological changes in this organ at
      a later stage.

PMID- 12226813
TI  - Combined biochemistry and histocytochemistry as a tool to investigate Ecto-ATPase
      in the cardiac muscle.
AB  - Ecto-ATPase (ecto-adenosine triphosphatase), a key enzyme of cardiac metabolism,
      is responsible for modulation of the concentration of extracellular nucleotides
      in the heart. We present methodology consisting of the combined use of
      biochemical and histocytochemical techniques to study its properties. Using
      samples from essentially the same preparation, we applied biochemistry and
      histocytochemistry to determine biochemical characteristics of ecto-ATPase and an
      in situ localization of its reactivity. Our results indicated that detected
      enzyme resists fixation, depends on divalent ions, and hydrolyzes ATP, but not
      AMP or ADP-beta-S. Reaction product of the enzyme activity was found confined to
      the extracellular surface of the plasma membrane of cardiac myocytes and
      endothelial cells due to the corresponding orientation of the enzyme active
      sites. Experiments using an inhibitor justified specificity of the reaction. When
      used together with molecular biological and immunocytochemical techniques, the
      present methodological approach should be capable of yielding important
      information about the actual ability of ecto-ATPase to operate.

PMID- 12226814
TI  - Antiretroviral drug resistance among HIV-1 infected children failing treatment.
AB  - High levels of HIV-1 replication occur following perinatal infection and
      antiretroviral drugs may not fully suppress viral load during the early years of
      childhood. Adherence to treatment may also be difficult among children. These two
      factors will contribute to development of drug resistance but limited paediatric
      data are available. This study has, therefore, evaluated the prevalence of drug
      resistance among children and assessed the contribution of adherence to failing
      therapy. Samples from 26 children who had experienced virological failure to
      antiretroviral therapy were tested for drug resistance using the Visible Genetics
      TRUGENE trade mark HIV-1 genotyping assay. HIV-1 subtype was determined using a
      peptide-based EIA and drug adherence determined by physician assessment. Twenty
      four children were black African, 23 of whom were infected with a non-B subtype.
      HIV RNA sequence data was obtained for 21 of the 26 children; at treatment
      failure resistance mutations were detected in the protease gene of 7 (33%) and
      the reverse transcriptase gene of 19 (90%). A lower proportion of children had
      evidence of drug resistance at nadir and no resistance mutations were detected
      prior to treatment. Genotypic resistance was common in those treated with
      lamivudine (10/11, 91%), nevirapine (6/8, 75%), and zidovudine (7/11, 64%). The
      prevalence of mutations was lower among those receiving other nucleoside reverse
      transcriptase inhibitors and protease inhibitors. In 50% of children, drug
      adherence was >90%. Antiretroviral drug resistance was common among this group of
      children failing therapy, the majority of whom were infected with non-B subtypes
      of HIV-1. As adherence to treatment was low in 50%, this was likely to be an
      important contributory factor.

PMID- 12226815
TI  - Virological and immunological effects of salvage therapy following treatment
      interruption and a shift in HIV-1 resistance genotype.
AB  - The circulating human immunodeficiency virus type 1 (HIV-1) population of
      patients in whom many prior therapy regimens have failed often undergo a shift
      from a drug-resistant virus to a wild-type virus following interruption of
      treatment. This study analyses the virological and immunological effects of
      salvage therapy following treatment interruption and a shift from a drug
      resistance genotype. Twenty-one HIV-1 infected patients who had genotype
      reversion by population-based sequencing after 3 months of treatment interruption
      were given a new salvage regimen consisting of 3-5 drugs selected according to
      their treatment history. Seven (33%) of 21 patients who had fewer than 200 HIV-1
      RNA copies/ml until month 12 were defined as virological responders. Four
      patients were transient responders and 10 were nonresponders. The virological
      responders were more frequently CDC group A and had higher CD4 + T lymphocyte
      counts at the time of treatment resumption. The peripheral blood T CD4 + and T
      CD8 + lymphocyte populations of the patients declined significantly during
      treatment interruption. Only virological responders showed significant increases
      in their CD4 + T lymphocyte count 12 months after treatment resumption and these
      counts rapidly returned to pre-interruption baseline values in most of these
      patients. Treatment interruption could be useful for optimising salvage therapy
      for patients previously given many failing regimens. However, controlled trials
      are needed to assess the clinical benefit of this strategy.

PMID- 12226816
TI  - Prevalence and profile of mutations associated with lamivudine therapy in Indian
      patients with chronic hepatitis B in the surface and polymerase genes of
      hepatitis B virus.
AB  - Lamivudine results in the selection of resistant hepatitis B virus (HBV)
      variants. Because the surface gene of HBV overlaps completely the polymerase
      gene, the incidence and profile of surface and polymerase gene mutations were
      investigated prospectively in chronic HBV patients who were on lamivudine
      therapy. Twenty-six patients with chronic liver disease confirmed histologically
      were included in this study. Extracted HBV DNA from sera samples were subjected
      to PCR amplification for the mutation prone regions of the surface and polymerase
      genes of the HBV genome. The emergence of mutant forms and biochemical
      derangements were studied carefully during the course of the therapy. In six of
      26 (23%) patients, mutations emerged on lamivudine therapy. YM552I/VDD resistant
      mutants were observed in one (6%) and five (29%) patients at Month 12 and 18,
      respectively, out of 17 patients, who had completed more than 9 months of
      therapy. The mean time of emergence of resistance was 16.4 +/- 6.8 months. In
      three of the five patients, emergence of YM552I/VDD mutation was accompanied with
      a rise in HBV DNA levels. In two patients, mutations were noticed at the end of
      the viral breakthrough; when the DNA level went down to undetectable levels (<0.5
      pg/mL). In two patients, normal ALT levels were found at the time of emergence of
      the YMDD mutation. YM552I/VDD mutations were observed in 43% of HBeAg positive
      and 20% of anti-HBe positive patients (P = ns). Although the 'a'-determinant
      region was found to be unaffected; in one patient, a novel pattern due to
      emergence of YIDD mutant was observed; the corresponding aa in the S-ORF turned
      to a stop codon. In summary, the frequency of emergence of YM552I/VDD mutations
      was 29% at Month 18 in the Indian patients. The presence of normal ALT and low
      levels of HBV DNA do not exclude the existence of resistant mutants. Novel
      mutations in the S-ORF, which lead to premature surface gene termination might
      affect the production of HBsAg and need further study.

PMID- 12226817
TI  - Genetic variation of hepatitis B surface antigen coding region among infants with
      chronic hepatitis B virus infection.
AB  - Variants in the amino acid composition of the primary antibody-binding site of
      hepatitis B surface antigen (HBsAg) have been identified in a number of
      populations with chronic hepatitis B virus (HBV) infection. Direct sequencing of
      amplified or cloned PCR products, solid phase detection of sequence-specific PCR
      products (SP-PCR), and limiting dilution cloning PCR (LDC-PCR) were compared to
      determine their sensitivity in detecting differing concentrations of HBsAg
      variants. LDC-PCR had the greatest sensitivity and could detect HBsAg variants at
      a concentration of 0.1% of the total viral population. HBsAg variants were
      detected in 51% of infants with chronic HBV infection acquired after postexposure
      prophylaxis, and more than half of the variants were detected only by the most
      sensitive methods.

PMID- 12226818
TI  - Two distinct types of hepatitis B virus core promoter variants in Yemeni blood
      donors.
AB  - Genetic variations in the basic core promoter (BCP) region of hepatitis B virus
      (HBV) occur during the natural history of chronic HBV infection. This study
      investigates the presence of basic core promoter variations in 28 asymptomatic
      Yemeni blood donors, correlating variations with HBeAg phenotype and viral load.
      The core promoter/precore and surface gene region of HBV DNA were amplified using
      nested PCRs and the PCR products were sequenced either directly or after cloning.
      HBeAg and viral load were measured when HBV DNA was detectable. Sequencing of 18
      surface PCR products indicated that all were of genotype D. Two distinct types of
      variants were identified in the basic core promoter: substitution only (N = 14)
      and major deletion (N = 9). The commonest substitutions were located at
      nucleotide positions 1753, 1762, and 1764; 10/14 (71.4%) were associated with the
      precore 1896A substitution resulting in the premature stop of the precore reading
      frame and 6/14 (42.9%) had viral loads above 400 copies/ml. Two forms of deletion
      variants were found: 8 bp deletion (1763-1770) (N = 2) and a novel 12 (1746-1757)
      + 8 bp (1763-1770) deletion (N = 7). The deletion sequences were never associated
      with the precore 1896A substitution and all had viral load below 400 copies/ml
      with negative HBeAg phenotype. The polymorphism 1773C was found in 9/14 (64.3%)
      substitution sequences whereas all deletion sequences had 1773T. Two donors had
      mixed sequences of basic core promoter substitution and major deletions (both 8
      bp and 12 + 8 bp). While the deletion variants in these two donors were similar
      to others found in isolation, the substitutions were of a different pattern.
      Further studies are required to understand the selection process behind these
      variants.

PMID- 12226819
TI  - Hepatitis C virus particles of different density in the blood of chronically
      infected immunocompetent and immunodeficient patients: Implications for virus
      clearance by antibody.
AB  - The purpose of this study was to analyse the influence of the humoral immune
      response on the generation and clearance of hepatitis C virus (HCV) RNA
      containing particles in the blood of chronically infected patients. Blood samples
      were fractionated by sequential flotation ultracentrifugation and HCV RNA was
      recovered in three fractions: low density of < 1.063 g/ml, intermediate density
      of 1.063-1.21 g/ml, and high density of > 1.21 g/ml. Serum low-density
      lipoproteins co-fractionated with the low-density particles, and high-density
      lipoproteins co-fractionated with the intermediate-density particles.
      Immunoglobulins were found exclusively in the high-density fractions. In patients
      with congenital immunodeficiencies, with no or low serum antibodies to the virus,
      mean HCV RNA titres were equal in each fraction, at approximately 10(5) IU/ml. In
      antibody-positive, immunocompetent patients, however, virus titres in the low
      density fraction and those in the high-density fraction were reduced or absent in
      most patients, suggesting that virus particles in these fractions are subject to
      antibody-mediated clearance. Particles of intermediate density were approximately
      equal in titre in both patient groups, suggesting that these particles are
      neither generated by, nor cleared, as a result of the humoral immune response.
      Immunoprecipitation experiments indicated that particles of intermediate density
      were not complexed with either high-density lipoprotein or immunoglobulins.
      Elucidation of the mechanisms by which these particles are generated and
      maintained in the blood may provide valuable insight into the mechanism of virus
      persistence.

PMID- 12226821
TI  - Changing molecular epidemiology of hepatitis C virus infection in Northeast
      Italy.
AB  - To assess HCV genotype distribution and its determinants, 318 consecutive HCV RNA
      positive patients were examined. Subtype 1b infection was the most prevalent
      (35.5%), followed by subtype 1a (22%), 3a (21.4%) and 2 genotype (21.3%).
      Subtypes 1a, 1b and 3a had a comparable prevalence (30-35%) in the 0-15-, 16-30-
      and 31-45-year age groups. In subjects older than 45 years, genotype 2 prevalence
      increased, whereas subtype 1a and 3a infections decreased markedly. In this age
      group types 1b and 2 accounted for a prevalence of more than 90% in a comparable
      proportion. Genotype prevalence rates according to different risk factors were
      different statistically (P < 0.001): subtype 1a and 3a infections were
      predominant in injection drug users (42.9% and 37.7%, respectively), whereas
      community acquired infections and infections in patients with a history of
      transfusion were caused mainly by subtype 1b (38.5% and 66.6%, respectively).
      Logistic regression showed that age and injection drug use are independent
      determinants of genotype distribution.

PMID- 12226820
TI  - Evaluation of the clinical usefulness of COBAS AMPLICOR HCV MONITOR assay
      (ver2.0): Comparison with AMPLICOR HCV MONITOR assay (ver1.0) and HCV core
      protein level.
AB  - The quantitation of serum levels of hepatitis C virus (HCV) RNA in chronic
      hepatitis C has been regarded as one of the most important indicators for the
      outcome of interferon (IFN) therapy. The AMPLICOR HCV MONITOR version 1.0
      (AMPLICOR v1.0) assay is widely used for the evaluation of the HCV level. A new
      generation assay called the COBAS AMPLICOR HCV MONITOR version 2.0 (COBAS v2.0)
      assay, which is semiautomated and modified to amplify all genotypes equally, has
      been developed. The aim of this study was to evaluate the clinical relevance of
      the COBAS v2.0 assay in comparison with the AMPLICOR v1.0 assay and HCV core
      protein assay in patients with chronic hepatitis C before IFN therapy. HCV RNA
      was detectable in 230 cases (97.5%) and undetectable in 6 cases (2.5%) by the
      COBAS v2.0 assay. The RNA levels measured by the AMPLICOR v1.0 assay correlated
      significantly with those measured by the COBAS v2.0 assay, and the sensitivity of
      the new version 2.0 assay was better than that of version 1.0, especially in
      serotype 2. In relation to the outcome of IFN therapy, HCV RNA levels from
      virologically sustained responders by the AMPLICOR v1.0 assay were 82.3 +/- 22.9
      kcopies/ml in serotype 1 and 36.9 +/- 13.4 kcopies/ml in serotype 2, and those
      from virologically nonsustained responders were 525.2 +/- 48.6 kcopies/ml in
      serotype 1 and 76.7 +/- 19.5 kcopies/ml in serotype 2. The rates of sustained
      response to <100 kcopies/ml were 34/63 (54.0%) in serotype 1 and 24/48 (50.0%) in
      serotype 2. A statistically significant virological response was seen in serotype
      1 (P < 0.0001), but not in serotype 2. In contrast, the levels in virologically
      sustained responders by the COBAS v2.0 assay were 88.2 +/- 20.5 KIU/ml in
      serotype 1 and 136.8 +/- 40.1 KIU/ml in serotype 2, and those in virologically
      nonsustained responders were 608.8 +/- 48.4 KIU/ml in serotype 1 and 328.3 +/-
      62.8 KIU/ml in serotype 2. The rates of sustained response to <100 KIU/ml were
      33/60 (55.0%) in serotype 1 and 21/35 (60.0%) in serotype 2. Statistical
      significance in virological response was seen in both serotype 1 (P < 0.0001) and
      serotype 2 (P < 0.05). Although the sensitivity of the HCV core protein assay was
      lower than that with the COBAS v2.0 assay, the HCV core protein levels also
      correlated well with the results of the COBAS v2.0 assay. The HCV core protein
      levels of virologically sustained responders were 37.6 +/- 12.0 pg/ml in serotype
      1, 81.3 +/- 37.0 pg/ml in serotype 2, and those of virologically nonsustained
      responders were 289.9 +/- 23.5 pg/ml in serotype 1, 191.4 +/- 32.1 pg/ml in
      serotype 2. This assay could predict the outcome of IFN therapy in both serotype
      1 (P < 0.0001) and serotype 2 (P < 0.05). Thus, both the COBAS v2.0 assay and the
      HCV core protein assay showed that the viral load was an indicator of
      virologically sustained response in serotype 2 and in serotype 1.

PMID- 12226822
TI  - High prevalence of GB virus C/hepatitis G virus genotype 3 among autochthonous
      Venezuelan populations.
AB  - GB virus C or hepatitis G virus (GBV-C/HGV) is highly prevalent among population
      groups at risk of parenterally transmitted viral agents, but it has also a
      worldwide distribution in other non-risk population groups. GBV-C/HGV RNA and
      antibodies against its envelope protein (anti-E2 Abs) were found in 3/86 (3%) and
      7/89 (8%) of biomedical science personnel (BSP), in 31/453 (7%) and 37/200 (19%)
      of blood donors (BD), and in 6/64 (9%) and 26/59 (44%) of hemodialysis patients
      (HD) from Caracas, Venezuela. A significant gradient of GBV-C/HGV exposure (anti
      E2 Abs and/or GBV-C/HGV RNA) was found between BSP (lowest prevalence), BD, and
      HD (P < 0.001). GBV-C/HGV RNA and anti-E2 Abs were also found in 2/69 (2.9%) and
      2/44 (4.5%) of individuals from a rural community, in 9/162 (5.5%) and 2/40 (5%)
      of West Amerindians, and in 14/56 (25%) and 4/53 (7.5%) of South Amerindians.
      Socioeconomic and cultural factors may have contributed to the relatively high
      risk of exposure to GBV-C/HGV in BD and Amerindians. Whereas GBV-C/HGV genotypes
      1 (n = 1), 2 (n = 6), and 3 (n = 22) were present in Venezuela, only the Asiatic
      genotype 3 was found infecting Amerindians and rural populations (n = 16).
      Genotype assignment based on the 5' noncoding region of the GBV- C/HGV genome was
      corroborated in some isolates by genetic analysis of the E2 region. This report
      confirms the circulation of the Asiatic genotype of GBV-C/HGV among Amerindians,
      suggesting an old origin of GBV-C/HGV. This might be associated with the
      apparently low pathogenesis of this virus.

PMID- 12226823
TI  - Detection of cytomegalovirus DNA in human placenta.
AB  - Although human cytomegalovirus (CMV) is one of the most common causes of viral
      intrauterine and perinatal infection, its distribution in the placenta is poorly
      understood. The purpose of this study was to determine the frequency of CMV DNA
      positivity in placentas, to demonstrate the localization of the viral genome, and
      to identify the clinical features related to placental CMV. A total of 254
      placentas from 231 mothers were investigated, and the maternal serum CMV
      immunoglobulin antibodies were measured. Specimens from both the placental
      parenchyma and the placental membrane close to the ruptured site in each placenta
      were examined for the presence of CMV DNA using dot blot hybridization after PCR
      amplification. None of 57 placentas from seronegative mothers was positive for
      CMV DNA. Of 197 placentas from seropositive mothers, 60 (30.5%) had CMV DNA in
      either the parenchyma or the membrane by dot blot analysis. In situ hybridization
      was carried out on these 60 placentas, and the localization of the viral genome
      was established in 19; CMV DNA was localized mostly to the villi, including the
      mesenchyme and trophoblasts, extravillous trophoblasts, and decidual cells. The
      mean gestational age at delivery was significantly later in the CMV DNA-positive
      placentas than in the negative placentas (36.9 +/- 5.1 vs 34.7 +/- 6.2 weeks, P =
      0.0059). CMV DNA was detected in only 6 of 33 placentas delivered in the second
      trimester, and all six were associated with either severe maternal nephritis or
      severe chorioamnionitis. These results suggest that the CMV genome is common in
      placentas at later gestational ages and in those of earlier gestational ages with
      certain maternal complications.

PMID- 12226824
TI  - Antibody responses to Epstein-Barr virus-encoded latent membrane protein-1 (LMP1)
      and expression of LMP1 in juvenile Hodgkin's disease.
AB  - A large group of juvenile Hodgkin's disease patients (n = 242, mean age 11.7
      years, 75% [n = 181] seropositive) was evaluated for anti-Epstein-Barr virus
      (EBV) antibody responses and the presence of EBV-encoded EBER-RNA and latent
      membrane protein-1 (LMP1)-protein expression in the tumor. The molecular
      diversity of anti-EBV antibody responses in Hodgkin's disease patients with EBV
      positive and-negative tumors was studied by enzyme-linked immunosorbent assay
      (ELISA) and immunoblot. Using purified recombinant LMP1 protein as antigen, the
      presence of antibodies to LMP1 was related to expression of LMP1 in the tumor
      cells and specific EBV-serological patterns. Antibodies to LMP1 were detected in
      30% of the EBV-seropositive Hodgkin's disease patients. The presence of
      antibodies to LMP1 was not associated with a distinct anti-EBV antibody diversity
      profile (ELISA), but a significantly higher percentage of patients with
      antibodies to LMP1 had antibodies to ZEBRA and viral capsid antigen (VCA)-p18
      (Immunoblot). Significantly more patients with an EBV-positive tumor had
      detectable antibody responses to LMP1, but the presence of antibodies to LMP1 did
      not reflect the expression of LMP1 protein in the tumor cells. Interestingly, all
      patients with the strongest antibody responses to LMP1 had EBV-negative tumors,
      suggesting immunological selection in vivo.

PMID- 12226825
TI  - Epstein-Barr virus (types 1 and 2) in the tear film in Sjogren's syndrome and HIV
      infection.
AB  - Evidence of Epstein-Barr virus (EBV) shedding in the saliva and tear film has
      been sought to explain the pathogenesis of the oral and ocular features of
      Sjogren's syndrome. Patients with human immunodeficiency virus (HIV) infection
      are purported to have a higher incidence of keratoconjunctivitis sicca. Twenty
      patients with definite Sjogren's syndrome (primary and secondary), 19 with HIV
      infection, and 15 normal controls were recruited and studied. Human herpes
      viruses (EBV 1 and 2, CMV, HZV, and HSV-1) in tear film were detected by
      polymerase chain reaction of DNA extracted from Schirmer strips. HSV-1, VZV, and
      CMV were not detected in any tear samples. EBV-1 DNA was found in the tear film
      of 4 patients with Sjogren's syndrome, which was not significantly different from
      the control group (P = 0.18). Twelve patients with HIV infection had evidence of
      EBV-1 in their tears, which was significantly different from controls (P =
      0.0002) and patients with Sjogren's syndrome (P = 0.014). EBV-2 was found in 3
      patients with HIV and in 1 patient with secondary Sjogren's syndrome, and was
      always found as a co-infection with EBV-1 (P = 0.01). This represents the first
      report examining EBV types 1 and 2 in the tear film and also EBV in the tear film
      of patients with HIV. Shedding of EBV in the tear film was not related to the
      presence of keratoconjunctivitis sicca in Sjogren's syndrome. EBV-2 co-infection
      with EBV-1 has not been previously reported in the tear film. EBV infection is
      abnormally regulated in Sjogren's syndrome and HIV, and it is likely that the
      presence of EBV in the tear film is related to the patients' altered immune
      status.

PMID- 12226826
TI  - Epstein-Barr virus-associated gastric carcinoma in southern India: A comparison
      with a large-scale Japanese series.
AB  - Epidemiological and clinicopathological features of Epstein-Barr virus (EBV)
      associated gastric carcinoma was compared in India and Japan, two countries
      differing markedly in gastric cancer incidence. Using in situ hybridization
      assay, the presence of EBV-encoded small RNA (EBER) was examined in 215, and
      2,011 gastric cancer cases in Kerala, India, and Japan, respectively. Ten cases
      (5%), all males, in the Indian series were EBER-positive. This frequency was
      similar to that in the Japanese series (6.2%). As was the case with Japanese
      series, the EBV-associated gastric carcinoma in the Indian series was observed
      most frequently in the middle part of the stomach (1 in antrum, 4 in middle part,
      2 in cardia, and 3 unknown), and, histologically, the diffuse type Lauren's
      classification (8 cases) was more common than the intestinal type (2 cases).
      Virus subtyping by PCR-RFLP revealed that all of the 10 EBV strains isolated from
      the EBER-positive Indian cases were subtype A, and wild-type F for Bam HI F
      region. In Bam HI I region, 8 cases were type C and the remaining 2 cases were
      type D. In either series, there was no significant difference in the frequency of
      tumors with p53 overexpression between EBER-positive and -negative cases.
      However, the proportion of cells with p53 overexpression in EBER-negative tumors
      was significantly higher than that in EBER-positive tumors regardless of
      histological type in both series. In conclusion, the frequency and major
      clinicopathological features of EBV-associated gastric carcinoma in south India
      were similar to those observed in Japanese series although gastric cancer
      incidence in these two countries differs markedly.

PMID- 12226827
TI  - Molecular epidemiology of human calicivirus gastroenteritis outbreaks in Hungary,
      1998 to 2000.
AB  - Between November 1998 and November 2000, 196 stool specimens from 21 outbreaks of
      acute nonbacterial gastroenteritis occurring in 11 of the 19 counties of Hungary
      were collected and tested for human caliciviruses. Human caliciviruses were
      detected and characterized by a type-common enzyme-linked immunosorbent assay
      (EIA) and reverse transcription-polymerase chain reaction (RT-PCR) followed by
      cloning and sequencing. Twenty (95%) and 14 (67%) outbreaks were positive by EIA
      and RT-PCR, respectively, and 12 RT-PCR-positive outbreaks were also confirmed by
      sequencing. Comparative sequence analysis revealed 13 Norwalk-like virus
      sequences in the 12 outbreaks, including 11 Norwalk-like virus genogroup II
      (seven in Hawaii-like, two Lordsdale-like, one Melksham-like, and one Hillingdon
      like) and two Norwalk-like virus genogroup I (related to Southampton-like and
      Desert Shield-like clusters) viruses. Multiple Norwalk-like virus clusters, with
      a predominance of Hawaii-like viruses, played an important role in nonbacterial
      gastroenteritis outbreaks during the study period. This is the first country-wide
      molecular epidemiological investigation of human calicivirus-associated,
      gastroenteritis outbreaks in Hungary and Central-Eastern Europe.

PMID- 12226828
TI  - Quantification of human herpesvirus 8 by real-time PCR in blood fractions of AIDS
      patients with Kaposi's sarcoma and multicentric Castleman's disease.
AB  - Few studies have assessed human herpesvirus 8 (HHV8) viremia levels in different
      HHV8-related pathologies, using sensitive and reproducible molecular assays. Our
      objective was to compare the HHV8 DNA load in serial blood samples (collected
      every 3 months for 1 year) from acquired immunodeficiency syndrome (AIDS)
      patients with Kaposi's sarcoma (KS) and multicentric Castleman's disease (MCD).
      The HHV8 viral load was determined in both peripheral blood mononuclear cells
      (PBMC) and plasma fractions, using a competitive real-time polymerase chain
      reaction (PCR) assay developed in a LightCycler instrument (Roche Diagnostics).
      In six subjects with limited or extensive KS while on highly active
      antiretroviral therapy, the HHV8 DNA load was either undetectable (<50
      copies/10(5) cells) or low (</=135 copies) in all PBMC samples. In contrast, the
      cellular HHV8 load was >1,000 copies in at least one of the samples from the two
      subjects with both KS and MCD. HHV8 DNA was detected in plasma only when the
      cellular viral load was >10,000 copies/10(5) cells. After chemotherapy, the HHV8
      DNA load became undetectable in the MCD patients despite no changes in CD4 T-cell
      counts or highly active antiretroviral therapy (HAART) regimens. These results
      suggest that the pathogenesis of the two HHV8-associated diseases (i.e., KS and
      MCD) might be different, as only the latter was associated with important viremia
      in our patients.

PMID- 12226829
TI  - Human interleukin-6 induces human herpesvirus-8 replication in a body cavity
      based lymphoma cell line.
AB  - Human herpesvirus-8 (HHV-8) is etiologically associated with Kaposi's sarcoma
      (KS), body cavity-based lymphoma (BCBL), and multicentric Castleman's disease
      (MCD). These HHV-8-associated diseases arise predominantly in acquired
      immunodeficiency syndrome (AIDS) patients. Human interleukin-6 (huIL-6) elevated
      in the serum of AIDS patients is suggested to stimulate the growth of KS and BCBL
      and to augment the symptoms of MCD. To determine whether huIL-6 stimulates HHV-8
      replication directly, expression of the HHV-8 ORF-50 immediate-early gene
      (transcription activator) and ORF-26 late lytic gene (a capsid protein) was
      assessed in a BCBL-1 cell line stimulated by huIL-6 by means of real-time reverse
      transcription-polymerase chain reaction. huIL-6 induced both ORF-50 and ORF-26
      expression, and the maximal ORF-50 expression appeared earlier than that of ORF
      26. The data indicate that huIL-6 reactivates HHV-8 in BCBL-1 cells through
      inducing ORF-50. We also confirmed the previously reported activities of HHV-8
      encoded huIL-6 homologue (viral interleukin-6 [vIL-6]) on human immunodeficiency
      virus (HIV) replication in U1 cell line and huIL-6 production by MT-4 T cells,
      and utilizing monoclonal antibodies to the huIL-6 receptor components, we
      elucidated that gp130 is the signaling molecule necessary for these vIL-6
      activities. These data suggest the possible existence of interaction between HIV
      and HHV-8 via IL-6, and that the blockade of IL-6 signal by anti-IL-6R antibody
      or anti-gp130 antibody can constitute a strategy to treat HIV/HHV-8 dually
      infected patients.

PMID- 12226830
TI  - Detection of human papillomavirus in esophageal carcinoma.
AB  - The aim of the study was to assess the prevalence of human papillomavirus (HPV)
      in the esophagus in the coastal region of Eastern Guangdong, Southern China, an
      area with a high incidence of esophageal carcinoma. Fresh surgical resection
      esophageal specimens were obtained from 176 esophageal carcinoma patients
      admitted to the Tumor Hospital of Shantou University Medical College. The samples
      were subjected to polymerase chain reaction (PCR) to detect HPV infection using
      consensus and type-specific primers for HPV type 6, 11, 16, and 18. The incidence
      rate was 65.5%, 69.1%, and 60% in tissues of cancerous, paracancerous and normal
      mucosa, respectively. Further analysis of the distribution of HPV types in the
      three sections of tissues showed that the high-risk HPV types 16 and 18 were
      found mainly in the cancer cells (43.2%), whereas the low-risk HPV types 6 and 11
      were seen mainly in the normal mucosa (52.3%). The total infection rate of the
      high-risk HPV types 16 and HPV 18 was the highest in cancerous tissues (54.5%),
      followed by paracancerous tissues (19.5%), and the lowest in normal mucosa
      (11.7%). There was high incidence of HPV infection in the esophageal epithelium
      in Eastern Guangdong, Southern China, where esophageal carcinoma is prevalent.
      HPV was seen in the normal, paracancerous and cancerous tissues, with the high
      risk HPV type 16 and 18 more common in cancerous tissues. The results indicate
      that the high incidence of esophageal carcinoma in this area is associated with
      HPV infection.

PMID- 12226831
TI  - Comparisons of HPV DNA detection by MY09/11 PCR methods.
AB  - Two modifications to the original L1 consensus primer human papillomavirus (HPV)
      PCR method, MY09-MY011, using AmpliTaq DNA polymerase (MY-Taq), were evaluated
      for HPV DNA detection on clinical specimens from a cohort study of cervical
      cancer in Costa Rica. First, HPV DNA testing of 2978 clinical specimens by MY09
      MY011 primer set, using AmpliTaq Gold DNA polymerase (MY-Gold) were compared with
      MY-Taq testing. There was 86.8% total agreement (kappa = 0.72, 95%CI = 0.70-75)
      and 69.6% agreement among positives between MY-Gold and MY-Taq. MY-Gold detected
      38% more HPV infections (P < 0.0001) and 45% more cancer-associated (high-risk)
      HPV types (P < 0.0001) than MY-Taq, including 12 of the 13 high-risk HPV types.
      Analyses of discordant results using cytologic diagnoses and detection of HPV DNA
      by the Hybrid Capture 2 Test suggested that MY-Gold preferentially detected DNA
      positive specimens with lower HPV viral loads compared with MY-Taq. In a separate
      analysis, PGMY09-PGMY11 (PGMY-Gold), a redesigned MY09/11 primer set, was
      compared with MY-Gold for HPV DNA detection (n = 439). There was very good
      agreement between the two methods (kappa = 0.83; 95%CI = 0.77-0.88) and
      surprisingly no significant differences in HPV detection (P = 0.41). In
      conclusion, we found MY-Gold to be a more sensitive assay for the detection of
      HPV DNA than MY-Taq. Our data also suggest that studies reporting HPV DNA
      detection by PCR need to report the type of polymerase used, as well as other
      assay specifics, and underscore the need for worldwide standards of testing.

PMID- 12226832
TI  - The woodchuck interferon-alpha system: Cloning, family description, and biologic
      activity.
AB  - Interferon-alpha (IFN-alpha) is a key element in the defense against viral
      infection because, in addition to a direct antiviral effect, it exhibits potent
      immunostimulatory activity. To investigate the function of this cytokine in the
      woodchuck model of chronic hepatitis B, the woodchuck IFN-alpha gene (IFNA)
      family was cloned and examined. The data indicate that this is a multigenic
      family from which 12 IFNA functional sequences and four pseudogene sequences were
      isolated. The overall identity of the amino acid sequence among the members of
      the woodchuck IFN-alpha family is 85%, and the identity with the IFN-alpha family
      from other species such as mice and humans is 50%. The analysis of hepatic
      expression of IFNA genes showed that wIFNA5a was the subtype transcribed
      preferentially in the woodchuck liver. The wIFNA genes transcribed in the liver
      were tested in an eukaryotic expression system and were found to enhance 2-5
      oligoadenylate synthetase (2-5-OAS) mRNA levels and to posses a potent antiviral
      activity. Cloning of woodchuck IFNA genes will allow testing diverse forms of IFN
      alpha delivery as well as different combination therapies in woodchuck hepatitis
      virus infection, thus providing useful information for the design of new
      strategies for the treatment of patients with chronic hepatitis B.

PMID- 12226833
TI  - Measles virus strains circulating in Central and West Africa: Geographical
      distribution of two B3 genotypes.
AB  - Africa remains one of the major reservoirs of measles infection. Molecular
      epidemiological studies have permitted different measles virus isolates to be
      grouped into clades and genotypes; the major group, which has been identified as
      indigenous to Africa, is clade B. The viruses from epidemics in the Gambia (1993)
      and in the Cameroon (2001) were examined. In both studies, the homogeneity of the
      virus isolates within the epidemic as shown by sequence analysis revealed less
      than 0.2% variation of nucleotides between isolates. The measles viruses isolated
      in 1983 in Yaounde, Cameroon, were designated as the B1 genotype. However, in
      2001 only viruses belonging to the B3 genotype were found in this city. The
      viruses in the Gambia (1993) were also of the B3 genotype. However, these viruses
      could be distinguished from each other at the antigenic level and by comparative
      sequence analysis. The B3 Cameroon (2001) viruses were related to the proposed
      B3.1 subgroup, whereas the Gambian (1993) isolates corresponded to the B3.2
      subgroup. The geographical distribution for the period 1993-2001 of these two
      viruses shows that B3.1 is found from the Sudan to Nigeria and Ghana extending
      south to the Cameroon, whereas the B3.2 genotype is found in West Africa. In
      Nigeria and Ghana, the viruses co-circulate. The identification of these viruses
      will permit more meaningful epidemiological studies after the proposed increase
      in measles vaccination coverage.

PMID- 12226835
TI  - Isolation of vaccine-derived type 1 polioviruses displaying similar properties to
      virulent wild strain Mahoney from sewage in Japan.
AB  - Type 1, 2, and 3 vaccine-derived polioviruses were isolated from a sewage
      disposal plant located downstream of the Oyabe River in Toyama Prefecture, Japan,
      between October 1993 and September 1995. Neurovirulence was analyzed in 13 type 1
      vaccine-derived strains, using mutant analysis by polymerase chain reaction and
      restriction enzyme cleavage (MAPREC). Nine strains (69%) were estimated to have
      marked neurovirulence. Some of the neutralizing antigenic sites, temperature
      sensitivity, and plaque-forming ability of two virulent vaccine-derived
      poliovirus strains were similar to Mahoney strain. The neutralizing activity of
      human sera obtained after oral poliomyelitis vaccine (OPV) administration against
      one of the virulent vaccine-derived polioviruses was examined. Although all human
      sera showed sufficient neutralizing activity for the prevention of poliomyelitis
      by vaccine-derived poliovirus strains, a lower titer than that against Sabin type
      1 strain was observed. Vaccination against virulent vaccine-derived poliovirus
      will be effective. However, the environmental presence of viruses that have
      properties similar to those Mahoney strain is a threat. The introduction of
      inactivated poliovirus vaccine (IPV), and well-maintained herd immunity, together
      with reinforced environmental surveillance is important for the final phase of
      the polio eradication program by the World Health Organization (WHO).

PMID- 12226834
TI  - Genetic analysis of measles viruses isolated in Morocco.
AB  - Sequence analysis was conducted on the hemagglutinin (H) and nucleoprotein (N)
      genes from nine wild-type measles viruses (MV) isolated during an outbreak that
      occurred in Morocco during 1998 and 1999. The sequence data showed that all the
      viruses were closely related to each other and were members of genotype C2.
      Genotype C2 has been shown to be circulating in Europe, and the sequences of the
      Moroccan isolates were most closely related to the sequences of recent viral
      isolates from western Europe. This report presents the first molecular
      epidemiological study of circulating wild-type measles viruses in Morocco.
      Knowledge of the indigenous strain of measles virus circulating in Morocco will
      help to describe viral transmission pathways and should contribute to efforts to
      evaluate the effectiveness of future vaccination campaigns.

PMID- 12226836
TI  - Molecular epidemiological analysis of community circulating respiratory syncytial
      virus in rural South Africa: Comparison of viruses and genotypes responsible for
      different disease manifestations.
AB  - Human respiratory syncytial virus (RSV) is a major cause of severe lower
      respiratory tract infection in children in both the industrialized and developing
      world. Most molecular epidemiological studies have, until now, focused on
      isolates from hospitalized infants in industrialized countries. Limited data have
      been available with regard to community circulating RSV, especially from Africa.
      The present study compares RSV isolates from infants attending rural community
      clinics in the Northern province of South Africa, with isolates from hospitalized
      infants in Soweto, near Johannesburg, South Africa, during the same period. A
      multiplex nested polymerase chain reaction was developed for analyzing the
      clinical specimens, a technique that permits subtyping and nucleotide sequence
      analysis of the second variable region of the G-protein gene. Community- and
      hospital-based isolates from young children in South Africa, as well as isolates
      from Mozambique were compared phylogenetically. One subgroup B community isolate
      was identified that had a G-protein truncated by approximately 35 amino acids,
      however, the other community isolates were not significantly different from
      hospital isolates. Evidence was found that the same RSV genotypes and viruses
      could cause mild upper respiratory tract infections or lower respiratory tract
      infections or severe RSV in young infants.

PMID- 12226837
TI  - A review of the terms agglomerate and aggregate with a recommendation for
      nomenclature used in powder and particle characterization.
AB  - The terms "agglomerate" and "aggregate" are widely used by powder technologists
      to describe assemblages of particles that are found in dry powders and powders in
      liquid suspensions. Each term has a specific meaning but, unfortunately, they are
      frequently interchanged at will and this has resulted in universal confusion.
      This confusion is perpetuated by conflicting definitions in national and
      international standards and this presents problems when describing powder
      properties or communicating results in reports and research papers. This paper
      reviews the current status of the definitions, with particular emphasis on their
      use in the pharmaceutical industry. It is proposed that just one term,
      agglomerate, should be used to describe an assemblage of particles in a powder
      and that the term aggregate should be confined to pre-nucleation structures.

PMID- 12226838
TI  - Effect of interferons on P-glycoprotein-mediated rhodamine-123 efflux in cultured
      rat hepatocytes.
AB  - The effect of interferon (IFN)-beta and IFN-gamma on P-glycoprotein (P-gp)
      mediated efflux of rhodamin-123(Rho-123), a typical substrate of P-gp, was
      studied in rat hepatocytes in primary culture. After treatment with IFN-beta, IFN
      gamma, or both for 3 days, steady-state levels of Rho-123, incorporated into the
      hepatocytes, were measured to evaluate the P-gp activity. Whereas IFN-beta did
      not affect the intracellular level of Rho-123, IFN-gamma treatment caused a
      significant increase of the level, suggesting that IFN-gamma treatment suppresses
      the expression of P-gp or its activity. A combination of the two types of IFN
      exhibited a similar effect to that of IFN-gamma alone. The effect of IFN-gamma
      was still observed in the presence of H(2)O(2), which enhances the expression and
      activity of P-gp. Immunoblot analysis using a monoclonal antibody C219 revealed,
      however, that P-gp expression was increased after treatment with IFN-gamma, but
      only slightly by IFN-beta treatment. These results suggest that the enhanced Rho
      123 uptake of rat primary hepatocytes induced by IFN-gamma does not result from
      reduced expression of P-gp but, rather, from impaired maturation or dysfunction
      of the efflux transporter.

PMID- 12226839
TI  - Alkaline hydrolysis of oxaliplatin--isolation and identification of the oxalato
      monodentate intermediate.
AB  - The alkaline degradation of the chemotherapeutic agent oxaliplatin has been
      studied using liquid chromatography. The oxalato ligand is lost in two
      consecutive steps. First, the oxalato ring is opened, forming an oxalato
      monodentate intermediate, as identified by electrospray ionization mass
      spectrometry. Subsequently, the oxalato ligand is lost and the dihydrated
      oxaliplatin complex is formed. The observed rate constants for the first step
      (k(1)) and the second step (k(2)) follow the equation k(1) or k(2) = k(0) + k(OH(
      ) )[OH(-)], where k(0) is the rate constant for the degradation catalyzed by
      water and k(OH(-) ) represents the second-order rate constant for the degradation
      catalyzed by the hydroxide ion. At 37 degrees C the rate constants for the first
      step are k(OH(-) ) = 5.5 x 10(-2) min(-1) M(-1) [95% confidence interval (CI),
      2.7 x 10(-2) to 8.4 x 10(-2) min(-1) M(-1)] and k(0) = 4.3 x 10(-2) min(-1) (95%
      CI, 4.0 x 10(-2) to 4.7 x 10(-2) min(-1)). For the second step the rate constants
      are k(OH(-) ) = 1.1 x 10(-3) min(-1) M(-1) (95% CI, -1.1 x 10(-3) to 3.3 x 10(
      3)) min(-1) M(-1) and k(0) = 7.5 x 10(-3) min(-1) (95% CI, 7.2 x 10(-3) to 7.8 x
      10(-3) min(-1)). Thus, the ring-opening step is nearly six times faster than the
      step involving the loss of the oxalato ligand.

PMID- 12226840
TI  - Spray-freeze-drying for protein powder preparation: particle characterization and
      a case study with trypsinogen stability.
AB  - This work investigates the use of spray freeze-drying (SFD) to produce protein
      loaded particles suitable for epidermal delivery. In the first part of the study,
      the effects of formulation and process conditions on particle properties are
      examined. Aqueous solutions of trehalose produce SFD particles in the size range
      20-80 microm, with a smooth, textured surface, but having high internal porosity.
      The latter was visualized using SEM and a novel particle embedding and sectioning
      technique. Use of an annealing step during the freeze-drying cycle caused the
      particles to shrink, reducing hereby porosity and also the measured rate of
      moisture uptake into these amorphous particles. SFD pure mannitol was
      approximately 40% amorphous, but not hygroscopic. Incorporation of dextran 37,500
      into a combined amorphous trehalose/mannitol formulation led to increased
      particle shrinkage and lower particle porosity on annealing. The model protein
      trypsinogen lost approximately 15% activity during SFD of solutions containing 50
      mg/mL protein, but was only marginally aggregated (1.4%). It is suggested that
      trypsinogen forms an irreversible partially unfolded state or molten globule on
      SFD/rehydration. The pure protein was also partially inactivated without
      aggregation during atomization into air. Surprisingly, neither activity loss nor
      aggregation were detected on atomization of the protein solution into liquid
      nitrogen. Quench-freezing of small droplets may reverse the partial unfolding of
      trypsinogen occurring on atomization into air. The origin of the trypsinogen
      inactivation during SFD must therefore be the subsequent freeze-drying step of
      this multistep process. Isolated freeze drying of trypsinogen produces strong
      aggregation and equivalent inactivation. This result suggests that trypsinogen
      behaves differently during freeze drying from frozen droplets and from bulk
      solution in a vial. In the former case the protein forms an irreversible
      partially unfolded state, whereas in the latter case aggregates are formed.
      Trypsinogen inactivation during SFD could be completely prevented by the presence
      of trehalose in the formulation. Electron Spectroscopy for Chemical Analysis
      (ESCA) showed a high surface excess of the protein in the SFD particles, which
      was reduced on inclusion of Polysorbate 80, but not trehalose. Taken together,
      these results help to elucidate the complex destabilization behavior of
      trypsinogen during SFD.

PMID- 12226841
TI  - Effect of guanidino modification and proline substitution on the in vitro
      stability and blood-brain barrier permeability of endomorphin II.
AB  - Endomorphin II (ENDII), an endogenous ligand for the mu-opioid receptor, was
      investigated as a possible analgesic with fewer side effects than morphine. To
      improve CNS entry of END II, structural modification was also examined to
      determine whether Pro(4) substitution and cationization affected physico-chemical
      characteristics, blood-brain barrier (BBB) transport, and analgesic profile. END
      II and its Pro(4)-substituted analog, Morphiceptin (MOR), were cationized by
      guanidino (GU)-addition. MOR was seven times less lipophilic than END II, whereas
      GU-addition decreased lipophilicity of both peptides. MOR did not affect in vitro
      BBB permeability; however, GU-addition increased permeability of MOR by 31%. MOR
      decreased protein binding by 23% compared to END II, whereas GU-addition
      increased protein binding of both peptides by 71 and 113%, respectively. MOR
      increased brain t(1/2) compared to END II. GU-addition significantly increased
      t(1/2) of MOR and END II in both brain (sixfold and 10-fold, respectively) and
      serum (over 10-fold). Pro(4)-substitution and GU-addition enhanced the in vivo
      analgesia profiles of i.v. administered END II and MOR, but decreased i.c.v.
      analgesia profiles. This study demonstrates Pro(4)-substitution decreases protein
      binding and enhances brain stability while cationization enhances both brain and
      serum stability with variable effects on BBB permeability. The analgesic profiles
      show that both Pro(4)-substitution and cationization enhance i.v. analgesia and
      thus, are promising structural modifications for the development of successful
      opioid drugs.

PMID- 12226842
TI  - Water vapor absorption into amorphous hydrophobic drug/poly(vinylpyrrolidone)
      dispersions.
AB  - Water vapor absorption isotherms were measured for three amorphous hydrophobic
      drug/poly(vinylpyrrolidone) (PVP) dispersions in the concentration range 10-90%
      w/w PVP. Experimental isotherms were compared to predicted isotherms calculated
      using each individual component isotherm multiplied by its weight fraction.
      Indomethacin (IMC)/PVP, ursodeoxycholic acid (UDCA)/PVP and indapamide (IDP)/PVP
      amorphous dispersions all exhibited experimental isotherms reduced relative to
      predicted isotherms indicating that dispersion formation altered the water vapor
      absorption properties of the individual components. For all three drug/PVP
      systems, deviation from predicted water uptake was greatest close to the 1:1
      drug:PVP monomer composition, indicating that intermolecular interaction in
      amorphous dispersions affects the water uptake properties of the individual
      components. Using dry glass transition temperature (T(g)) data, the extent of
      drug/PVP interaction was shown to be greatest in the IDP/PVP system, which could
      explain why the largest reduction in water vapor absorption was found in this
      system. The plasticizing effect of absorbed water varied according to dry
      dispersion PVP content in all systems and the resulting nonideal changes in free
      volume, calculated using the Vrentas model, were greatest close to the 1:1
      drug:PVP monomer composition. A three-component Flory-Huggins model successfully
      predicted isotherms for IMC/PVP compositions from 60 to 90% w/w PVP and
      identified an IMC-PVP interaction parameter chi in the range 1.27-1.49, values
      that suggest poor homogeneity of mixing in the dry system. These data indicate
      that amorphous dispersion formation causes both chemical and physical changes in
      the individual amorphous components that can have a significant effect on their
      water vapor absorption properties.

PMID- 12226843
TI  - Dissolution kinetics of single crystals of alpha-lactose monohydrate.
AB  - The dissolution kinetics of alpha-lactose monohydrate (alphaLM) single crystals
      were studied by a flow-cell method at different undersaturations. Linear
      dissolution profiles were obtained as a function of time for all the faces except
      the (010) face. The dissolution rates, obtained from these profiles, were
      anisotropic and varied considerably with undersaturation. At low undersaturations
      (0-2%), the order of dissolution rate was (110) > (100) > (011) = (110) > (010).
      This order changed with increasing undersaturation (>5%) to (011) >> (100) >
      (110) > (110) > (010). In alphaLM crystals in which lattice strain was induced by
      synchrotron X-irradiation, the rates of dissolution of all faces increased with
      increasing strain. The increase was less significant for the (011) faces than for
      the remainder. Under this constraint, the (010) face became the fastest
      dissolving one and the [011]face became the slowest one. The results of all
      experiments are explained on the basis that although dislocations may act as
      initiating dissolution centers at very low undersaturations, these sources
      rapidly give way to two-dimensional nucleation of randomly distributed
      dissolution sites as the undersaturation is increased. Under these conditions,
      which better reflect the normal dissolution processes of materials, bulk lattice
      strain plays the most significant role in defining the dissolution rate. The
      results show a potential route to the controlled engineering of the dissolution
      behavior of crystalline materials.

PMID- 12226844
TI  - Water sorption and glass transition behaviors of freeze-dried sucrose-dextran
      mixtures.
AB  - The water sorption and glass transition behaviors of freeze-dried disaccharide
      polysaccharide mixtures at various contents were investigated at relative
      humidities (RHs) of 0, 11, 23, and 33%. Sucrose and three types of dextrans,
      which differ in molecular weight, were used as model di- and polysaccharides,
      respectively. The relationship between the dextran and water contents of the
      sucrose-dextran mixture at different constant RHs indicated that a mixture of
      sucrose and dextran was lower than that calculated by the Lang and Steinberg mass
      balance equation. In the RH range of 0-23%, the glass transition temperature,
      T(g), increased to a considerable extent when the dextran content was equal to or
      higher than 50%, while the increase in T(g) at dextran contents lower than 50%
      was small. A marked increase in T(g) was observed at RH 33% for dextran contents
      of 0-25% as well as in the range above 50%. This suggests that the physical
      stability of the highly hydrated amorphous disaccharide is effectively
      strengthened by the addition of a small amount of polysaccharide. These
      tendencies were similar for the three dextrans of different molecular weights.
      Furthermore, it was demonstrated that the addition of a small amount of dextran
      is quite effective in preventing the collapse of amorphous sugar during freeze
      drying.

PMID- 12226845
TI  - Soft contact lenses capable of sustained delivery of timolol.
AB  - The aim of this work was to evaluate the influence of the composition and the
      application of an imprinting technique on the loading capability of weakly
      crosslinked hydroxyethyl methacrylate (HEMA) hydrogels, with a view to their use
      as reloadable soft contact lenses for administration of timolol. Hydrogels were
      prepared by dissolution of ethylene glycol dimethacrylate (EGDMA, 10 mM) in HEMA
      with or without methacrylic acid (MAA) or methyl methacrylate (MMA; 100-400 mM)
      and with or without timolol maleate (10 mg/mL), initiation of polymerization by
      addition of 2,2'-azo-bis(isobutyronitrile) (AIBN, 10 mM), injection in molds, and
      curing in an oven at 50-70 degrees C. Unreacted reagents were removed by boiling.
      The dry hydrogels were clear and fully polymerized with smooth, poreless surfaces
      and presented optimal mechanical properties. The hydrogels were then
      characterized by determination of their swelling and timolol release kinetics in
      0.9% NaCl, phosphate buffer (pH 7.4) and artificial lacrimal fluid, and of the
      timolol loading capacity of both nonimprinted hydrogels and de-timololized
      imprinted hydrogels at various pHs. Both water uptake and timolol release
      exhibited Fickian kinetics, except in the case of hydrogels made with 400 mM MAA.
      Timolol diffusion into 0.9% NaCl from HEMA or HEMA/MMA was slow; release from
      HEMA/MAA into phosphate buffer or lacrimal fluid was faster and increased with
      the MAA content of the polymer. Timolol loading was significant for HEMA/MAA
      hydrogels (imprinted or not) at pH 5.5-7.5, and specially for imprinted hydrogels
      containing 100 mM MAA, which absorb 12 mg timolol/g dry hydrogel. The results
      indicate that the incorporation of MAA as comonomer increases the timolol loading
      capacity to therapeutically useful levels while retaining appropriate release
      characteristics.

PMID- 12226846
TI  - Solid state characterization of E2101, a novel antispastic drug.
AB  - E2101, a novel antispastic drug, was found to exist in at least two polymorphs
      that were confirmed by X-ray powder diffraction (XRD). These two species are
      designated forms I and II. The physicochemical and thermodynamic properties of
      these polymorphs were characterized by variable temperature XRD, thermal
      analysis, hygroscopicity measurements, and dissolution studies. The transition
      temperature was also estimated from the solubilities determined at various
      temperatures. The E2101 polymorphs were anhydrous and adsorbed little moisture
      under high humidity conditions. The melting onsets and heats of fusion for form I
      were 148.1 +/- 0.2 degrees C and 38.2 +/- 1.0 kJ/mol, respectively, and for form
      II were 139.8 +/- 0.4 degrees C and 35.2 +/- 0.5 kJ/mol, respectively. The
      intrinsic dissolution rate of form II in JP 2 medium was 1.5-fold faster than
      that of form I, corresponding to the rank order of the aqueous solubility and the
      enthalpy of fusion. Accordingly, form I was thought to be thermodynamically more
      stable than form II and thus suitable for further development. According to the
      thermal analysis and variable temperature XRD results, the recrystallization of
      form I occurred at approximately 145 degrees C after form II melted, however, no
      crystal transition behavior was observed below the lower melting point. The DSC
      thermograms at various heating rates and van't Hoff plots from the solubility
      studies indicated that the polymorphic pair would be monotropic.

PMID- 12226847
TI  - Different molecular motions in lyophilized protein formulations as determined by
      laboratory and rotating frame spin-lattice relaxation times.
AB  - The spin-lattice relaxation times in the laboratory and rotating frame (T(1) and
      T(1rho)) of protons and carbons in lyophilized bovine serum gamma-globulin
      formulation containing dextran were determined by (1)H solid-state pulsed nuclear
      magnetic resonance (NMR) and high-resolution (13)C solid-state NMR. The
      temperature dependence of T(1) and T(1rho) of dextran protons in the lyophilized
      formulation suggests that the correlation time, tau(c), of the methylene protons
      in dextran is approximately 10(-6) s at -100 degrees C and 60% relative humidity,
      and decreases to 10(-7) s at 0 degrees C. When temperature is increased from 0
      degrees C, the increased motion of the methylene groups is reflected in T(1), but
      is too fast to be observed by changes in T(1rho). Thus, the motion of the methine
      groups rather than the methylene groups begins to be reflected in T(1rho). The
      correlation time of the methine protons as determined by T(1rho) was of the same
      order as that of the methine carbons as determined by T(1rho). As the temperature
      is increased past the glass/rubber transition temperature, both the methylene and
      methine motions are greatly enhanced, resulting in much shorter T(1) and T(1rho)
      relaxation times.

PMID- 12226848
TI  - Cyclodextrin complexes of sulfonamide carbonic anhydrase inhibitors as long
      lasting topically acting antiglaucoma agents.
AB  - Complexes of several 1,3,4-thiadiazole-2-sulfonamide derivatives possessing
      strong carbonic anhydrase (CA) inhibitory properties with beta-cyclodextrin and
      hydroxypropyl-beta-cyclodextrin were obtained and characterized. Although the
      investigated CA inhibitors possessed very powerful inhibitory properties against
      the two CA isozymes involved in aqueous humor production within the eye, i.e., CA
      II and CA IV, these compounds were topically ineffective as intraocular pressure
      (IOP) lowering agents in normotensive/hypertensive rabbits, due to their very low
      water solubility. On the contrary, the cyclodextrin-sulfonamide complexes proved
      to be effective and long-lasting IOP lowering agents in the two animal models of
      glaucoma mentioned above.

PMID- 12226849
TI  - Stabilization of proteins by low molecular weight multi-ions.
AB  - A method is described to identify small molecule ligands that stabilize proteins.
      The procedure is based on the hypothesis that molecules of various sizes
      containing two to four charges should occasionally bind to unpaired charged sites
      on the surface of proteins and by crosslinking such residues stabilize the native
      state of the liganded protein. A simple turbidity assay is employed that detects
      inhibition of protein aggregation under selected sets of conditions. Eight test
      proteins were screened and in all cases specific ligands were identified that
      inhibited protein aggregation at millimolar to micromolar concentrations. Only
      small effects of these stabilizers on protein biological activities were found.
      In some, but not all cases, circular dichroism and fluorescence studies provided
      direct evidence of the binding of stabilizing ligands to the proteins suggesting
      multiple mechanisms of stabilization. This approach should be applicable to the
      development of excipients for the stabilization of pharmaceutical proteins and
      industrial enzymes as well as serve as starting points for second-generation
      inhibitors of increased affinity and specificity.

PMID- 12226850
TI  - Quantitative structure/property relationship analysis of Caco-2 permeability
      using a genetic algorithm-based partial least squares method.
AB  - Caco-2 cell monolayers are widely used systems for predicting human intestinal
      absorption. This study was carried out to develop a quantitative structure
      property relationship (QSPR) model of Caco-2 permeability using a novel genetic
      algorithm-based partial least squares (GA-PLS) method. The Caco-2 permeability
      data for 73 compounds were taken from the literature. Molconn-Z descriptors of
      these compounds were calculated as molecular descriptors, and the optimal subset
      of the descriptors was explored by GA-PLS analysis. A fitness function
      considering both goodness-of-fit to the training data and predictability of the
      testing data was adopted throughout the genetic algorithm-driven optimization
      procedure. The final PLS model consisting of 24 descriptors gave a correlation
      coefficient (r) of 0.886 for the entire dataset and a predictive correlation
      coefficient (r(pred)) of 0.825 that was evaluated by a leave-some-out cross
      validation procedure. Thus, the GA-PLS analysis proved to be a reasonable QSPR
      modeling approach for predicting Caco-2 permeability.

PMID- 12226851
TI  - Solid phases of tenoxicam.
AB  - In this report we describe the preparation and characterization of four
      polymorphic forms of tenoxicam; they are, three 1:1 stoichiometric solvates with
      acetonitrile, dioxane, and N,N-dimethylformamide, and an amorphous phase obtained
      by recrystallization in various solvents. Polymorph IV and solvates with dioxane
      and N,N-dimethylformamide are reported for the first time in this paper. In
      addition, three solvates were crystallized in acetone, ethyl acetate, and
      isopropyl alcohol. These solid forms were characterized by X-ray powder
      diffraction, differential scanning calorimetry, infrared spectroscopy,
      thermogravimetry, optical microscopy, and elemental analysis. Solid-state
      properties, intrinsic dissolution rate, and dissolution kinetics from formulated
      tablets are also provided.

PMID- 12226853
TI  - A diffusion-ordered NMR spectroscopy study of the solubilization of artemisinin
      by octanoyl-6-O-ascorbic acid micelles.
AB  - Artemisinin (QHS) is a natural drug with a very low solubility in water. To
      improve its availability in hydrophilic media, it was solubilized in micellar
      dispersions of octanoyl-6-O-ascorbic acid (ASC8), a relatively novel surfactant
      that combines surface activity with powerful performance as radical scavenger. In
      this article we report a study based on diffusion-ordered NMR spectroscopy (DOSY)
      measurements carried out on QHS/ASC8 micellar dispersions. QHS is efficiently
      solubilized by ASC8 micelles, with no significant perturbation of the
      micellisation.

PMID- 12226852
TI  - Peroxide formation in polysorbate 80 and protein stability.
AB  - Nonionic surfactants are widely used in the development of protein
      pharmaceuticals. However, the low level of residual peroxides in surfactants can
      potentially affect the stability of oxidation-sensitive proteins. In this report,
      we examined the peroxide formation in polysorbate 80 under a variety of storage
      conditions and tested the potential of peroxides in polysorbate 80 to oxidize a
      model protein, IL-2 mutein. For the first time, we demonstrated that peroxides
      can be easily generated in neat polysorbate 80 in the presence of air during
      incubation at elevated temperatures. Polysorbate 80 in aqueous solution exhibited
      a faster rate of peroxide formation and a greater amount of peroxides during
      incubation, which is further promoted/catalyzed by light. Peroxide formation can
      be greatly inhibited by preventing any contact with air/oxygen during storage. IL
      2 mutein can be easily oxidized both in liquid and solid states. A lower level of
      peroxides in polysorbate 80 did not change the rate of IL-2 mutein oxidation in
      liquid state but significantly accelerated its oxidation in solid state under
      air. A higher level of peroxides in polysorbate 80 caused a significant increase
      in IL-2 mutein oxidation both in liquid and solid states, and glutathione can
      significantly inhibit the peroxide-induced oxidation of IL-2 mutein in a
      lyophilized formulation. In addition, a higher level of peroxides in polysorbate
      80 caused immediate IL-2 mutein oxidation during annealing in lyophilization,
      suggesting that implementation of an annealing step needs to be carefully
      evaluated in the development of a lyophilization process for oxidation-sensitive
      proteins in the presence of polysorbate.

PMID- 12226854
TI  - Effect of a basic organic excipient on the dissolution of diclofenac salts.
AB  - Dissolution of diclofenac from compressed discs containing mixtures of a
      diclofenac salt and a basic excipient, in various w/w ratios, was examined. Two
      diclofenac salts, diclofenac deanol (DDNL) and diclofenac tert-butylamine, and
      the basic excipient 2-amino-2-methyl-1,3-propanediol (AMPD) were examined.
      Inclusion of the soluble basic excipient at high loadings enhanced the
      dissolution rate of diclofenac tert-butylamine fivefold; however, it retarded
      dissolution of the DDNL salt 40-fold in the weight fraction range 40-80% AMPD,
      despite the fact that AMPD is more than four times more soluble than DDNL. These
      findings were attributed to the solubilities of salts formed between diclofenac
      and the basic excipient used. The "salt conversion model" was developed to
      predict dissolution from mixtures of a salt of an ionizable drug and an ionizable
      excipient capable of forming a salt with the drug. Deviations from the model at
      high weight fractions of base and, in the case of the systems containing the more
      soluble drug, at low weight fractions of base were attributed to carrier
      controlled dissolution. The present work illustrates that the solubility of
      potential salts, which may form between the drug and ionizable excipients present
      has an important influence on the dissolution of the drug from such compressed
      mixtures.

PMID- 12226855
TI  - Application of multi-parameter flow cytometry using fluorescent probes to study
      substrate toxicity in the indene bioconversion.
AB  - The bioconversion of indene to cis-(1S,2R) indandiol, a potential key
      intermediate in the synthesis of Merck's HIV protease inhibitor, CRIXIVAN trade
      mark, can be achieved using a Rhodococcus strain. This study using Rhodococcus
      I24 reports on the application of multiparameter flow cytometry for the
      measurement of cell physiological properties based on cytoplasmic membrane (CM)
      integrity and membrane depolarization as indicators of toxic effects of the
      substrate, indene. Quantification of intact polarized CM, intact depolarized CM
      and permeabilized CM of a large population of bacterial cells has been conducted
      using specific intracellular and membrane-binding fluorescent stains.
      Measurements of oxygen uptake rate (OUR) and optical density (OD) as indicators
      of metabolic activity and biomass growth, respectively, were also made. Indene
      concentrations of up to 0.25 g/L (0.037 g indene/g dry cell weight) did not
      significantly (<5% compared to control) affect cell light-scattering properties,
      intact CM, membrane polarization, respiratory activity, or biomass growth.
      Between this value and 1.5 g/L (0.221 g indene/g dry cell weight), the changes in
      intact CM, respiratory activity and biomass growth were relatively insignificant
      (<5% compared to control), although dissipation of the membrane potential of a
      significant proportion of the cell population occurred at 0.50 g/L (0.074 g
      indene/g dry cell weight). At 2.5 g/L (0.368 g indene/g dry cell weight) there
      was a significant increase in the dead cell population, accompanied by changes in
      the extracellular cationic concentrations and substantial decrease in respiratory
      activity. The primary effect of indene toxicity was the disruption of the proton
      motive force across the cytoplasmic membrane which drives the formation of ATP.
      The disruption of the proton motive force may have been due to the measured
      changes in proton permeability across the membrane. In addition, indene may have
      directly inhibited the membrane-bound enzymes related to respiratory activity.
      The overall consequence of this was reduced respiratory activity and biomass
      growth. The cell physiological properties measured via flow cytometry are
      important for understanding the effects of toxicity at the cellular level which
      neither measurements of biomass growth or indandiol formation rates can provide
      since both are cell averaged measurements. The technique described here can also
      be used as a generic tool for measuring cell membrane properties in response to
      toxicity of other indene-resistant strains that may be possible to use as
      recombinant hosts to perform the biotransformation of indene. This study has
      demonstrated that flow cytometry is a powerful tool for the measurement of cell
      physiological properties to assess solvent toxicity on whole cell biocatalysts.

PMID- 12226856
TI  - Enhanced kinetic extraction of parvovirus B19 structural proteins.
AB  - Recombinant structural proteins (VP1 and VP2) of the human parvovirus B19 have
      been expressed simultaneously using the baculovirus expression system to form
      virus-like particles (VLPs) that have potential use as vaccines. In this study,
      we report optimization of extraction conditions to recover these VLPs from cell
      paste. Under hypotonic conditions with neutral pH these VLPs were poorly
      extracted (up to 3% extraction). Addition of reducing agents, detergents, salts,
      and sonication did not improve the extractability. While screening for conditions
      to improve the extractability of the VLPs, we discovered that a combination of
      higher pH and elevated processing temperature significantly increased the
      extraction. Whereas increasing pH alone increased extractability from 3% to 6%
      (pH increased from 8.0 to 9.5), the effect of elevated temperature was much more
      substantial. At 50 degrees C, we observed the extraction to be more than fivefold
      higher than that at room temperature (up to 25% extracted at pH 9.0). The
      kinetics of extraction at elevated temperatures showed a rapid initial rate of
      extraction (on the order of minutes) followed by a plateau. In addition, we
      compared the extraction of VP1 expressed alone. VP1 expressed alone is incapable
      of forming VLPs. We observed that non-VLP VP1 was easily extractable (up to 60%
      extracted) under conditions in which the VP1 + VP2 VLPs were not extractable.
      From these studies we conclude that parvovirus B19 structural proteins expressed
      to form VLPs have a hindered extractability as compared with non-VLP protein.
      This hindrance to extraction can be significantly reduced by processing at
      elevated temperatures and an increased pH, possibly due to the enhanced rates of
      solubilization and diffusion.

PMID- 12226857
TI  - Impact of cell culture process changes on endogenous retrovirus expression.
AB  - Cell culture process changes (e.g., changes in scale, medium formulation,
      operational conditions) and cell line changes are common during the development
      life cycle of a therapeutic protein. To ensure that the impact of such process
      changes on product quality and safety is minimal, it is standard practice to
      compare critical product quality and safety attributes before and after the
      changes. One potential concern introduced by cell culture process improvements is
      the possibility of increased endogenous retrovirus expression to a level above
      the clearance capability of the subsequent purification process. To address this,
      retrovirus expression was measured in scaled down and full production scaled
      Chinese hamster ovary (CHO) cell cultures of four monoclonal antibodies and one
      recombinant protein before and after process changes. Two highly sensitive,
      quantitative (Q)-PCR-based assays were used to measure endogenous retroviruses.
      It is shown that cell culture process changes that primarily alter media
      components, nutrient feed volume, seed density, cell bank source (i.e., master
      cell bank vs. working cell bank), and vial size, or culture scale, singly or in
      combination, do not impact the rate of retrovirus expression to an extent greater
      than the variability of the Q-PCR assays (0.2-0.5 log(10)). Cell culture changes
      that significantly alter the metabolic state of the cells and/or rates of protein
      expression (e.g., pH and temperature shifts, NaButyrate addition) measurably
      impact the rate of retrovirus synthesis (up to 2 log(10)). The greatest degree of
      variation in endogenous retrovirus expression was observed between individual
      cell lines (up to 3 log(10)). These data support the practice of measuring
      endogenous retrovirus output for each new cell line introduced into manufacturing
      or after process changes that significantly increase product-specific
      productivity or alter the metabolic state, but suggest that reassessment of
      retrovirus expression after other process changes may be unnecessary.

PMID- 12226858
TI  - Recombinant aprotinin produced in transgenic corn seed: extraction and
      purification studies.
AB  - Expression in transgenic plants is potentially one of the most economical systems
      for large-scale production of valuable peptide and protein products. However, the
      downstream processing of recombinant proteins produced in plants has not been
      extensively studied. In this work, we studied the extraction and purification of
      recombinant aprotinin, a protease inhibitor used as a therapeutic compound,
      produced in transgenic corn seed. Conditions for extraction from transgenic corn
      meal that maximize aprotinin concentration and its fraction of the total soluble
      protein in the extract were found: pH 3.0 and 200 mM NaCl. Aprotinin, together
      with a native corn trypsin inhibitor (CTI), was captured using a tryspin-agarose
      column. These two inhibitors were separated using an agarose-IDA-Cu2+ column that
      proved to efficiently absorb the CTI while the recombinant aprotinin was
      collected in the flowthrough with purity of at least 79%. The high purity of the
      recombinant aprotinin was verified by SDS-PAGE and N-terminal sequencing. The
      overall recombinant aprotinin recovery yield and purification factor were 49% and
      280, respectively. Because CTI was also purified, the recovery and purification
      process studied has the advantage of possible CTI co-production. Finally, the
      work presented here introduces additional information on the recovery and
      purification of recombinant proteins produced in plants and corroborates with
      past research on the potential use of plants as biorreactors.

PMID- 12226859
TI  - Proposed modifications to metabolic model for glycogen-accumulating organisms
      under anaerobic conditions.
AB  - Filipe et al. (2001) proposed an anaerobic metabolic model for glycogen
      accumulating organisms (GAO) in which the succinate-propionate pathway was used
      to describe the production of propionyl-CoA. However, propionyl-CoA is only an
      intermediate product in the above pathway. Stopping at propionyl-CoA instead of
      propionate (the end product of the pathway) results in the consumption of one ATP
      from succinate to succinyl-CoA, which was not accounted for in the model of
      Filipe et al. (2001). This resulted in significant errors in the stoichiometric
      coefficients in the final metabolic model. A modified model is presented in this
      communication and is shown to fit the experimental data significantly better than
      the original model.

PMID- 12226860
TI  - Novel electrochemical-enzymatic model which quantifies the effect of the solution
      Eh on the kinetics of ferrous iron oxidation with Acidithiobacillus ferrooxidans.
AB  - The influence of solution Eh on the rate of ferrous iron oxidation by
      Acidithiobacillus ferrooxidans is characterized. The experimental approach was
      based on the use of a two-chamber bioelectrochemical cell, which can determine
      the ferrous iron oxidation rate at controlled potential. Results enabled the
      formulation of a novel kinetic model, which incorporates the effect of solution
      Eh in an explicit form but still integrates the effect of ferrous iron
      concentration and ferric inhibition. The results showed that at Eh values below
      650 mV (standard hydrogen electrode, SHE) the bacterial oxidative activity is
      mainly dependent on ferrous iron concentration. At Eh values between 650 and 820
      mV (SHE) the oxidation rate is mainly controlled by ferric inhibition. Over 820
      mV (SHE) the bacterial oxidative activity is strongly inhibited by the Eh
      increase, being completely inhibited at Eh = 840 mV (SHE).

PMID- 12226861
TI  - Viscoelastic fluid description of bacterial biofilm material properties.
AB  - A mathematical model describing the constitutive properties of biofilms is
      required for predicting biofilm deformation, failure, and detachment in response
      to mechanical forces. Laboratory observations indicate that biofilms are
      viscoelastic materials. Likewise, current knowledge of biofilm internal structure
      suggests modeling biofilms as associated polymer viscoelastic systems. Supporting
      experimental results and a system of viscoelastic fluid equations with a linear
      Jeffreys viscoelastic stress-strain law are presented here. This system of
      equations is based on elements of associated polymer physics and is also
      consistent with presented and previous experimental results. A number of
      predictions can be made. One particularly interesting result is the prediction of
      an elastic relaxation time on the order of a few minutes-biofilm disturbances on
      shorter time scales produce an elastic response, biofilm disturbances on longer
      time scales result in viscous flow, i.e., nonreversible biofilm deformation.
      Although not previously recognized, evidence of this phenomenon is in fact
      present in recent experimental results.

PMID- 12226862
TI  - Modified model for the regulation of the tryptophan operon in Escherichia coli.
AB  - This article proposes a modification of the model developed by Sinha (1988) and
      Sen and Liu (1990) for the regulation dynamics of the tryptophan operon in E.
      coli based on a consistent overall balance of the agent repressing the mRNA
      transcription. The dynamics of the model are analyzed by means of continuation
      techniques and the influence of periodic fluctuations in the intracellular demand
      for tryptophan is addressed. The analysis provides deeper insight into the
      dynamics of this operon system and the results obtained may be a useful starting
      point for the optimization of tryptophan yield in bacterial cultures.

PMID- 12226863
TI  - Optimization of cardiac cell seeding and distribution in 3D porous alginate
      scaffolds.
AB  - Cardiac tissue engineering has evolved as a potential therapeutic approach to
      assist in cardiac regeneration. We have recently shown that tissue-engineered
      cardiac graft, constructed from cardiomyocytes seeded within an alginate
      scaffold, is capable of preventing the deterioration in cardiac function after
      myocardial infarction in rats. The present article addresses cell seeding within
      porous alginate scaffolds in an attempt to achieve 3D high-density cardiac
      constructs with a uniform cell distribution. Due to the hydrophilic nature of the
      alginate scaffold, its >90% porosity and interconnected pore structure, cell
      seeding onto the scaffold was efficient and short, up to 30 min. Application of a
      moderate centrifugal force during cell seeding resulted in a uniform cell
      distribution throughout the alginate scaffolds, consequently enabling the loading
      of a large number of cells onto the 3D scaffolds. The percent cell yield in the
      alginate scaffolds ranged between 60-90%, depending on cell density at seeding;
      it was 90% at seeding densities of up to 1 x 10(8) cells/cm(3) scaffold and
      decreased to 60% at higher densities. The highly dense cardiac constructs
      maintained high metabolic activity in culture. Scanning electron microscopy
      revealed that the cells aggregated within the scaffold pores. Some of the
      aggregates were contracting spontaneously within the matrix pores. Throughout the
      culture there was no indication of cardiomyocyte proliferation within the
      scaffolds, nor was it found in 3D cultures of cardiofibroblasts. This may enable
      the development of cardiac cocultures, without domination of cardiofibroblasts
      with time.

PMID- 12226864
TI  - Metabolic adaptation of Escherichia coli during temperature-induced recombinant
      protein production: 1. Readjustment of metabolic enzyme synthesis.
AB  - The metabolic burden and the stress load resulting from temperature-induced
      production of human basic fibroblast growth factor is connected to an increase in
      the respiratory activity of recombinant Escherichia coli, thereby reducing the
      biomass yield. To study the underlying changes in metabolic enzyme synthesis
      rates, the radiolabeled proteom was subjected to two-dimen- sional gel
      electrophoresis. After temperature-induction, the cAMP-CRP controlled
      dehydrogenases of the pyruvate dehydrogenase complex and the tricarboxylic acid
      cycle (LpdA and SdhA) were induced four times, reaching a maximum 1 h after the
      temperature upshift. The more abundant tricarboxylic acid cycle dehydrogenases
      (Icd and Mdh) were initially produced at reduced rates but regained preshift
      rates within 30 min. The adenylate energy charge dropped immediately after the
      temperature upshift but recovered within 1 h. Similar profiles in dehydrogenase
      synthesis rates and adenylate energy charge were found in a control cultivation
      of a strain carrying the "empty" parental expression vector. Although both
      strains exhibited significant differences in growth pattern and respiration rates
      after the temperature upshift, the adaptation of the energetic state of the cells
      and the synthesis of enzymes from the energy-generating catabolic pathway did not
      seem to be affected by the strong overproduction of the recombinant growth
      factor. In contrast, the synthesis rates of enzymes belonging to the biosynthetic
      machinery, e.g., translational elongation factors, decreased more strongly in the
      culture synthesizing the recombinant protein. In control and producing culture,
      synthesis rates of elongation factors paralleled the respective growth rate
      profiles. Thus, cells seem to readjust their metabolic activities according to
      their energetic requirements and, if necessary, at the cost of their biosynthetic
      capabilities.

PMID- 12226865
TI  - Metabolic adaptation of Escherichia coli during temperature-induced recombinant
      protein production: 2. Redirection of metabolic fluxes.
AB  - The impact of temperature-induced synthesis of human basic fibroblast growth
      factor (hFGF-2) in high-cell-density cultures of recombinant Escherichia coli was
      studied by estimating metabolic flux variations. Metabolic flux distributions in
      E. coli were calculated by means of a stoichiometric network and linear
      programming. After the temperature upshift, a substantially elevated energy
      demand for synthesis of hFGF-2 and heat shock proteins resulted in a redirection
      of metabolic fluxes. Catabolic pathways like the Embden-Meyerhof-Parnas pathway
      and the tricarboxylic acid (TCA) cycle showed significantly enhanced activities,
      leading to reduced flux to growth-associated pathways like the pentose phosphate
      pathway and other anabolic pathways. Upon temperature upshift, an excess of NADPH
      was produced in the TCA cycle by isocitrate dehydrogenase. The metabolic model
      predicted the involvement of a transhydrogenase generating additional NADH from
      NADPH, thereby increasing ATP regeneration in the respiratory chain. The
      influence of the temperature upshift on the host's metabolism was investigated by
      means of a control strain harboring the "empty" parental expression vector. The
      metabolic fluxes after the temperature upshift were redirected similarly to the
      production strain; the effects, however, were observed to a lesser extent and
      with different time profiles.

PMID- 12226866
TI  - Modelling of the enzymatic kinetically controlled synthesis of cephalexin:
      influence of diffusion limitation.
AB  - In this study the influence of diffusion limitation on enzymatic kinetically
      controlled cephalexin synthesis from phenylglycine amide and 7
      aminodeacetoxycephalosporinic acid (7-ADCA) was investigated systematically. It
      was found that if diffusion limitation occurred, both the synthesis/hydrolysis
      ratio (S/H ratio) and the yield decreased, resulting in lower product and higher
      by-product concentrations. The effect of pH, enzyme loading, and temperature was
      investigated, their influence on the course of the reaction was evaluated, and
      eventually diffusion limitation was minimised. It was found that at pH >or=7 the
      effect of diffusion limitation was eminent; the difference in S/H ratio and yield
      between free and immobilised enzyme was considerable. At lower pH, the influence
      of diffusion limitation was minimal. At low temperature, high yields and S/H
      ratios were found for all enzymes tested because the hydrolysis reactions were
      suppressed and the synthesis reaction was hardly influenced by temperature. The
      enzyme loading influenced the S/H ratio and yield, as expected for diffusion
      limited particles. For Assemblase 3750 (the number refers to the degree of enzyme
      loading), it was proven that both cephalexin synthesis and hydrolysis were
      diffusion limited. For Assemblase 7500, which carries double the enzyme load of
      Assemblase 3750, these reactions were also proven to be diffusion limited,
      together with the binding-step of the substrate phenylglycine amide to the
      enzyme. For an actual process, the effects of diffusion limitation should
      preferably be minimised. This can be achieved at low temperature, low pH, and
      high substrate concentrations. An optimum in S/H ratio and yield was found at pH
      7.5 and low temperature, where a relatively low reaction pH can be combined with
      a relatively high solubility of 7-ADCA. When comparing the different enzymes at
      these conditions, the free enzyme gave slightly better results than both
      immobilised biocatalysts, but the effect of diffusion limitation was minimal.

PMID- 12226867
TI  - Versatile method for production and controlled polymer-immobilization of
      biologically active recombinant proteins.
AB  - The immobilization of a protein by covalent attachment to a support matrix should
      involve only functional groups of the protein that are not essential for its
      biological activity. A general strategy for obtaining recombinant proteins
      designed for oriented covalent grafting onto copolymers was investigated. The
      rationale involves the definition of seven p24-derived recombinant proteins as
      fused to either distant or adjacent tags comprising primary amine rich tag
      consisting of six contiguous lysines suitable for oriented covalent
      immobilization and a hexa-histidine tag suitable for metal chelate affinity
      purification. High-level expression, efficient affinity purification, and
      coupling yields onto maleic anhydride-alt-methyl vinyl ether copolymers higher
      than 95% were obtained for all proteins. Afterwards, an investigation of the
      biological features of the immobilized vs. nonimmobilized protein onto the
      copolymer allowed us to select one bioconjugate which was used in a diagnostic
      context, i.e., as a capture antigen in an ELISA format test. Sera from 107 HIV
      seropositive individuals at various stages of HIV infection, including two
      seroconversion panels and 104 healthy HIV-seronegative controls, were tested
      using either RH24 or RK24H-copolymer coated onto the microtiter plate. These
      assays showed that the use of such a protein-copolymer bioconjugate allowed
      detection of lower antibody titers than the RH24 protein, illustrating the
      potential of applications of such doubly tagged proteins. Thus, a set of
      expression vectors was designed containing four different combinations of hexa
      lysine and hexa-histidine tags and a multiple cloning site, allowing the
      production of different recombinant fusion proteins suitable for biological
      reactivity conservation after immobilization.

PMID- 12226868
TI  - Effect of particle-particle shearing on the bioleaching of sulfide minerals.
AB  - The biological leaching of sulfide minerals, used for the production of gold,
      copper, zinc, cobalt, and other metals, is very often carried out in slurry
      bioreactors, where the shearing between sulfide particles is intensive. In order
      to be able to improve the efficiency of the bioleaching, it is of significant
      importance to know the effect of particle shearing on the rate of leaching. The
      recently proposed concept of ore immobilization allowed us to study the effect of
      particle shearing on the rate of sulfide (pyrite) leaching by Thiobacillus
      ferrooxidans. Using this concept, we designed two very similar bioreactors, the
      main difference between which was the presence and absence of particle-particle
      shearing. It was shown that when the oxygen mass transfer was not the rate
      limiting step, the rate of bioleaching in the frictionless bioreactor was 2.5
      times higher than that in a bioreactor with particle friction (shearing). The
      concentration of free suspended cells in the frictionless bioreactor was by
      orders of magnitude lower than that in the frictional bioreactor, which showed
      that particle friction strongly reduces the microbial attachment to sulfide
      surface, which, in turn, reduces the rate of bioleaching. Surprisingly, it was
      found that formation of a layer of insoluble iron salts on the surface of sulfide
      particles is much slower under shearless conditions than in the presence of
      particle-particle shearing. This was explained by the effect of particle friction
      on liquid-solid mass transfer rate. The results of this study show that reduction
      of the particle friction during bioleaching of sulfide minerals can bring
      important advantages not only by increasing significantly the bioleaching rate,
      but also by increasing the rate of gas-liquid oxygen mass transfer, reducing the
      formation of iron precipitates and reducing the energy consumption. One of the
      efficient methods for reduction of particle friction is ore immobilization in a
      porous matrix.

PMID- 12226869
TI  - How to turn change into opportunity for leadership.

PMID- 12226870
TI  - Patient education and the Web: what you see on the computer screen isn't always
      what you get in print.

PMID- 12226871
TI  - Quantum age: new rules for leaders.

PMID- 12226872
TI  - We can never look back.

PMID- 12226873
TI  - The power of fractals.

PMID- 12226874
TI  - Workshops help relieve caregivers of their cares.

PMID- 12226876
TI  - Turns around the clock.

PMID- 12226875
TI  - Essential skills.

PMID- 12226877
TI  - Lines of defence.

PMID- 12226878
TI  - Birth rights.

PMID- 12226879
TI  - Out in the cold.

PMID- 12226880
TI  - Open your mind.

PMID- 12226881
TI  - Stress-beating strategies.

PMID- 12226882
TI  - Male identity in mental health nursing.
AB  - AIM: To explore the cultural meaning associated with male mental health nurses.
      METHOD: An ethnographic approach was used to discover the meaning informants
      attach to the cultural norms, values and rules that govern their behaviour. Data
      were collected through participant observation and in-depth interviews with
      informants. RESULTS: Data were analysed using emerging domains and taxonomies
      regarding male nurse issues. This involved grouping terms, words and everyday
      reflections collected from the male mental health nurses. These lists of data
      (taxonomies) enabled the researcher to identify in-depth cultural themes about
      the attitudes, behaviours and symbolism typically associated with male nurses.
      CONCLUSION: A number of cultural themes emerged, including the notion of 'soft
      masculinity', which provided some insight into male nurses' experiences of
      working in a female-dominated workplace. A recurring theme was the need for male
      nurses to demonstrate gentleness and caring while maintaining a balanced sense of
      masculine identity.

PMID- 12226883
TI  - Providing culturally competent health services for ethnic minorities.
AB  - This article discusses the findings of a scholarship project aimed at gaining an
      understanding of the health needs of African and Caribbean older people and
      determining how these service-users perceive their needs are being met. It found
      that while practitioners were generally keen to provide a culturally appropriate
      service, some users thought their knowledge, attitudes and skills, particularly
      in communication, were a major source of concern.

PMID- 12226884
TI  - Feeding patients after abdominal surgery.
AB  - Nutrition in hospital has been the focus of negative attention in recent years.
      Apart from the issues surrounding older people and nutrition (Odlund-Olin et al
      1996), patients undergoing surgery might still be subject to inappropriate
      nutritional care and practice. Many are still fasted for long periods of time
      before surgery, and experience inappropriate regimes designed to wean them back
      onto normal eating and drinking patterns. This can lead to malnourishment and
      delayed healing. The author examines good practice in perioperative nutritional
      practice, designed to ensure that the patient recovers as quickly and as well as
      possible following abdominal surgery.

PMID- 12226885
TI  - The management of obesity.
AB  - With the ever increasing prevalence of obesity, it is a major priority in primary
      health care that effective strategies are implemented to curb this trend. This
      article aims to provide nurses with evidence-based guidelines for the treatment
      and prevention of obesity.

PMID- 12226886
TI  - Beneath the surface.

PMID- 12226888
TI  - How I get home in time for dinner.

PMID- 12226887
TI  - How a secret malpractice deal unraveled.

PMID- 12226889
TI  - Don't let lunch money bandits steal you blind.

PMID- 12226890
TI  - Sometimes we do things right.

PMID- 12226891
TI  - Tracy should still have her gallbladder.

PMID- 12226892
TI  - The changing face of hospital practice.

PMID- 12226893
TI  - Liability for peer review.

PMID- 12226894
TI  - Radiologic diagnosis and management of hyperacute stroke.

PMID- 12226895
TI  - Introduction to acute stroke imaging and intervention.

PMID- 12226896
TI  - Case of the season. Fournier's gangrene.

PMID- 12226897
TI  - Noncontrast conventional computed tomography in the evaluation of acute stroke.
AB  - The advantages of CT scanning in the assessment of hyperacute stroke patients
      include convenience, accuracy, speed, and low cost. CT scanning is presently
      considered to be the standard of care for the detection of acute extra-axial and
      parenchymal hemorrhage, although newer MRI techniques are challenging this claim.
      The accuracy of CT scanning for stroke detection can be optimized by the use of
      appropriate scanning technique, as well as interactive image review at a picture
      archiving and communication system workstation using narrow window and level
      settings. More importantly, CT scanning has prognostic value for patients
      receiving thrombolytic treatment by helping to predict both responses to
      treatment and hemorrhage risk. Finally, as will be discussed in other articles in
      this issue, CT angiography can be performed in the same imaging session as
      noncontrast CT scanning without substantially increasing the time required for
      patient evaluation. This provides data regarding vascular patency and tissue
      perfusion, which are valuable in the triage of stroke patients.

PMID- 12226898
TI  - Dynamic contrast-enhanced computed tomography of acute ischemic stroke: CTA and
      CTP.

PMID- 12226899
TI  - Conventional magnetic resonance imaging of acute stroke.

PMID- 12226900
TI  - Magnetic resonance angiography in acute stroke.

PMID- 12226901
TI  - Diffusion magnetic resonance imaging of acute ischemic stroke.

PMID- 12226902
TI  - Perfusion magnetic resonance imaging of acute ischemic stroke.

PMID- 12226903
TI  - Image-guided vascular recanalization in acute stroke.

PMID- 12226904
TI  - Up too late. Hectic lives rob kids of sleep and health.

PMID- 12226905
TI  - Releases of hazardous substances in schools: data from the Hazardous Substances
      Emergency Events Surveillance system, 1993-1998.
AB  - This report describes the adverse public-health effects resulting from releases
      of hazardous substances in schools. Data were analyzed from emergency events
      reported to the Hazardous Substances Emergency Events Surveillance (HSEES) system
      by 14 participating states during 1993-1998. Compared with all other types of
      events, a higher proportion of school-related events resulted in victims
      (relative risk [RR] = 3.94, 95 percent confidence interval [CI] = 3.37-4.60) and
      in evacuation (RR = 5.76, 95 percent CI = 5.16-6.43). The most common cause of
      these events was operator error, followed in frequency by equipment failure,
      improper mixing, and deliberate releases. The majority of victims were exposed to
      spills emitting noxious gases, and their resulting symptoms were primarily
      associated with the respiratory tract.

PMID- 12226906
TI  - Where we are in retail food safety, how we got to where we are, and how do we get
      there?
AB  - Food safety has not yet been attained. This is evident from reported foodborne
      disease outbreaks, laboratory-confirmed cases of diseases that can be foodborne,
      estimates of foodborne illness based on surveillance data, and out-of-compliance
      risk factors. Several activities have had an impact on food safety, but there are
      limitations in the way each of those activities has been or is being conducted.
      The activities include foodborne-disease surveillance; food sampling and testing;
      swabbing and testing of utensils; inspection and enforcement of regulations; use
      of the Food Code; on-site hazard analyses, on-site monitoring of critical control
      points and prompt corrective actions; applied research and challenge testing;
      training of public-health and food regulatory personnel; training of food
      workers, supervisors, and managers; and education of the public. To attain food
      safety, we must use common (microbiological) sense and understand the principles
      of transmission of foodborne-disease etiological agents and their control. A
      change of attitudes and program focus is necessary.

PMID- 12226907
TI  - More liability cases.

PMID- 12226908
TI  - An IR calibrator (a tool for the office) and a garage door safety stop pressure
      gauge (a tool for public relations).

PMID- 12226909
TI  - New research links poor air quality to increase in asthma cases.

PMID- 12226910
TI  - Urban air pollution linked to birth defects.

PMID- 12226911
TI  - School-related food poisonings rising 10 percent annually.

PMID- 12226912
TI  - An exposure assessment of PM10 from a major highway interchange: are children in
      nearby schools at risk?
AB  - In urban areas, elementary schools may be in close proximity to major roadways.
      Major roadways have been shown to be a significant source of particulate (PM10)
      air pollution. In several recent studies, particulate air pollution has been
      demonstrated to be an important factor associated with negative respiratory
      health effects, especially in minority children. In response to community
      concerns, during April 2000 the Office of Environmental Health and Safety of the
      Los Angeles Unified School District conducted an exposure assessment study in the
      East Los Angeles area, a region populated predominantly by ethnic minorities
      (predominantly Hispanic). The purpose of this study was to determine if children
      attending some of these schools are exposed to PM10 at sufficient levels to cause
      negative respiratory health effects. Results of this study show that students in
      close proximity to major roadways receive a dose of PM10 at levels approaching 10
      15 micrograms per cubic meter, an exposure predicted to cause negative health
      effects.

PMID- 12226913
TI  - [Interventional methods in the treatment of malignant conditions of the liver].
AB  - The article overviews vascular and percutaneous interventional methods used in
      the locoregional chemotherapy of liver tumors. It is based on experience from the
      treatment of 248 patients on the Radiodiagnostic clinic of the Teaching hospital
      in Brno (Bohunice department). Chemoembolization includes precisely aimed
      administration of cytostatics and a total ischaemization of the malignant tissue.
      Another method of locoregional chemotherapy is the administration of high doses
      of cytostatics into the afferent artery. Positive effect can be achieved only
      when the cytostatic perfuses all liver segments. Preoperative embolization of the
      portal vein represents an effective preliminary treatment of patients before the
      liver ablation. Percutaneous thermal ablation and the use of percutaneous ethanol
      injections are limited by the costs of treatment, by the number, size and
      location of tumors. Percutaneous ethanol injections are indicated in the
      treatment of hepatocellular carcinoma in the cirrhotic tissue. Percutaneous
      thermal ablation can effectively destroy foci in the liver up to the size of 5 cm
      without impairment of the surrounding tissue. Locoregional and percutaneous
      therapy of malignant liver processes represent alternative methods and individual
      approaches should be combined. Indication has to be carefully thought about by an
      interdisciplinary committee. It is necessary to realise that the aim is not to
      perform "technically precise operation" gut the lengths and quality of the
      patient's life.

PMID- 12226914
TI  - [Transitional elements and free radicals].
AB  - Iron and copper are essential trace elements, which in certain conditions, namely
      in the ionised form or in low-molecular complexes, can participate in single
      electron reactions and catalyse formation of free radicals, including the
      dangerous hydroxyl radical. Similar behavior have also some other transitive
      metals. Our overview is aimed on the role of transitive elements in the formation
      of free radicals and on the mechanisms that organisms have to prevent it. The
      highest attendance is given to the metabolism of iron and cooper. Consistent
      protection against free transitive metals (by binding with proteins, by oxidation
      or sequestration in a special compartment) enables organism to use their
      beneficial and required features without impairment of cell. Knowledge of these
      mechanisms provides the means to predict and effectively prevent the brake down
      of such defend systems in situations of the intravascular hemolysis,
      hemodialysis, administration of iron, impairments of the iron and copper
      metabolism, intoxication by oxidising substances etc.

PMID- 12226915
TI  - [Analysis of the inflammation reaction and selected indicators of immunity in
      patients with an infected diabetic ulcer].
AB  - BACKGROUND: Patients with diabetes represent 50 to 70% of patients who undergo
      nontraumatic foot or leg amputation, caused mostly by infection and necrosis of
      soft tissues accompanied with osteomyelitis. Signs and symptoms of infections may
      often be absent in patients with infected foot ulcers--the syndrome of "diabetic
      foot" (DF). The course and consequences of the infection may be influenced by the
      immune system dysfunction. The aim of our study was to assess presence of the
      chronic inflammation and specific immune responses, both humoral and cellular in
      patients with diabetic foot infection. METHODS AND RESULTS: 34 patients treated
      over one month for an infected DF in our foot clinic (mean age 54 +/- 8 years,
      mean duration of diabetes 20 +/- 9 years, mean HbAlc 8.8 +/- 1.5%), were matched
      with 27 healthy subjects. All patients were without clinical signs of acute deep
      foot infection and without critical leg ischemia. The inflammatory response was
      assessed by white blood cells count and C-reactive protein (CRP), humoral immune
      response was assessed by immunoglobulins (Ig) and cellular immunity was evaluated
      by T lymphocytes subpopulations. Patients with DF compared with healthy controls
      exhibited the laboratory signs of infection--significantly increased white blood
      cells count (7.6 +/- 2.1 vs. 6.4 +/- 1.3.10(9)/l, p < 0.01) and neutrophil count
      (4.6 +/- 1.8 vs. 3.8 +/- 0.9.10(9)/l, p < 0.05) and significantly increased CRP
      (7 +/- 12 vs. 2 +/- 6 mg/l, p < 0.01). Patients with DF had also significantly
      higher IgA levels (3.5 +/- 1.6 vs. 2.7 +/- 1.1 g/l, p < 0.05) and significantly
      more CD3+ T cells (76 +/- 8 vs. 71 +/- 10%, p < 0.05) and suppressor/cytotoxic
      CD8+ T cells (32 +/- 11 vs. 26 +/- 10%, p < 0.05). Other followed parameters IgG,
      IgM and serum monocyte and lymphocyte counts, CD4+ helper T cells and CD4+/CD8+ T
      cell ratio did not differ between patients with DF and healthy controls.
      CONCLUSIONS: We did not anticipate a severe secondary immunodeficiency in
      followed cellular and humoral immune parameters in patients with chronic
      bacterial foot infection. It is necessary to assess the sufficiency of immune
      system activation with respect to chronic inflammation in next research.

PMID- 12226916
TI  - [Importance of determining serologic markers in patients with celiac disease].
AB  - BACKGROUND: Coeliac disease is presently considered to be an autoimmune disorder.
      Basis for the diagnosis is the invasive histochemical examination of the
      intestinal biopsy. Pathologic changes are classified into three grades according
      to the villous atrophy. Due to the autoimmune process, the patients serum levels
      of the specific and nonspecific antibodies, more which easily accessible to
      investigation, are increase. METHODS AND RESULTS: One hundred thirty six probands
      (32 with coeliakia, 72 with other gastrointestinal disorders and 32 healthy ones)
      were included into the study. The antiendomysial, antireticular and antigliadin
      antibodies were examined. Results were compared with the histological finding in
      the gut sample. The highest sensitivity was found for antigliadin IgA antibodies
      (81%) and antiendomysial antibodies (75%). High specificity of the reaction in
      healthy subjects as well as in those with other gastrointestinal disorders (up to
      100%), was found for antiendomysial and antireticular antibodies. CONCLUSIONS:
      The most appropriate screening test the diagnosis of coeliac disease, appears to
      be the examination of the antigliadin antibodies of the class IgA and that of
      antiendomysial antibodies. On the basis of serology, today's high rate of
      underdiagnosing the disease can be prevented. However, the tests cannot
      differentiate between different degrees of the histological damage of the gut.

PMID- 12226917
TI  - [Exercise cardiorespiratory parameters in children motivated to physical activity
      after treatment for acute lymphoblastic leukemia].
AB  - BACKGROUND: Children treated for acute lymphoblastic leukemia (ALL) with
      anthracycline antibiotic agents must be followed up for the danger of late
      cardiotoxic effects of the treatment. Another threat represents the consequence
      of the protective upbringing and inactive lifestyle. The aim of present study was
      to assess the exercise cardiorespiratory indexes and anthropometric variables in
      previously treated children without clinical, ECG and echocardiographic signs of
      cardiotoxicity, who had been motivated to physical activity. METHODS AND RESULTS:
      29 children (12.3 +/- 2.7 years old) previously treated for ALL with
      anthracyclines were examined. The cumulative dosis of anthracyclines was 224 +/-
      39.4 mg/m2. The treatment was finished before 4.8 +/- 2.1 years and after this
      period no signs of the late cardiotoxicity were detectable. Both children and
      their parents were encouraged to the regular physical activity of submaximal
      intensity. 29 age- and sex-matched control subjects were healthy children, never
      limited in their activities, but without special physical training. As soon as
      the basic anthropometric data had been verified, both groups completed a
      progressive exercise test with the assessment of submaximal and maximal
      spiroergometric indexes. In all parameters followed we failed to prove any
      significant differences between the two groups. The treated children exhibited
      only slightly lower body height, higher body weight and higher percentage of body
      fat. They reached lower respiratory exchange ratio (R), with higher oxygen uptake
      on both submaximal and maximal load levels. CONCLUSIONS: When sufficiently
      motivated, children surviving five years after the treatment with anthracycline
      for ALL, who have no signs of cardiotoxic effects, have their functional
      cardiorespiratory capacity approximately comparable to that of healthy children.

PMID- 12226918
TI  - [Immunology at the Institute of Clinical and Experimental Medicine (IKEM)].

PMID- 12226919
TI  - [Correlation between gaseous exchange rate, body temperature, and mitochondrial
      protein content in the liver of mice].
AB  - Correlative and regressive relations between the gaseous exchange,
      thermoregulation and mitochondrial protein content were analyzed by two- and
      three-dimensional statistics in mice. It has been shown that the pair wise linear
      methods of analysis did not reveal any significant correlation between the
      parameters under exploration. However, it became evident at three-dimensional and
      non-linear plotting for which the coefficients of multivariable correlation
      reached and even exceeded 0.7-0.8. The calculations based on partial
      differentiation of the multivariable regression equations allow to conclude that
      at certain values of VO2, VCO2 and body temperature negative relations between
      the systems of gaseous exchange and thermoregulation become dominating.

PMID- 12226920
TI  - [The influence of extracellular pH on volume-activated chloride current in the
      prostate cancer epithelial cells].
AB  - The influence of extracellular pH on characteristics of volume-activated chloride
      current, ICl,swell, in the human prostate cancer epithelial cell line, LNCaP, was
      studied using the patch-clamp technique. Acidification of the extracellular
      hypotonic solution used to develop the current shortened the temporal parameters
      of ICl,swell development and reduced its maximal density. Sudden shifts of the pH
      towards acidification caused fast, transient potentiation of the current followed
      by its sustained inhibition. Voltage-dependent inactivation of ICl,swell was the
      most pronounced in the narrow range of pH = 6-7. Based on the analysis of our
      data we hypothesize that volume-regulated anion channels underlying ICl,swell
      possess in their structure at least two pH-sensitive molecular groups with
      similar pK = 6, titration of which modulates the current amplitude and two
      additional proton-sensitive groups that determine channel's inactivation.

PMID- 12226921
TI  - [Comparative analysis of calcium accumulation in tissues of the brain and the
      liver in alimentary hypercholesteremia].
AB  - Some mechanisms of changing calcium content in brain and liver at alimentary
      hypercholesteremia were studied. Dynamics of calcium accumulation in tissues of
      the organs under exploration has proved its contribution to an adaptive reaction
      of the organism at alimentary stress and reflected peculiarities of its different
      stages. Similar and simultaneous dynamic changes in calcium accumulation in both
      organs (liver and brain) seem to be induced by stereotypical pathogenic
      mechanisms. The results contribute much to the current ideas of the pathogenesis
      of alimentar hypercholesteremia.

PMID- 12226922
TI  - [Endothelium-dependent contractile reactions of vascular smooth muscles and
      content of oxygen free radicals in aging rats].
AB  - Endothelium-dependent and endothelium-independent reactions of vascular smooth
      muscles were studied in isolated preparations of thoracic part of aorta and
      portal vein of rats of two age groups--6.8 mo. (control) and 24-26 mo. (old
      animals). In old rats the disturbances occurred primarily in endothelium
      dependent vascular reactions. This age-related dysfunction of endothelium
      resulted in inhibition of NO-dependent regulation of vascular tone. Age-related
      changes in the state of plasmic membranes of erythrocytes were established using
      a method of acid hemolysis. Age-related changes in the levels of active forms of
      oxygen (.O2-, H2O2, .OH-) and nitrogen (NO2-, NO3-) were determined in the
      myocardium, aorta, blood plasma and erythrocytes of adult and old animals.

PMID- 12226923
TI  - [Characteristics of cardiohemodynamics and endothelium-dependent vascular
      reactivity in highlanders].
AB  - The present investigation was designed to study cardiohemodynamics and
      endothelium-dependent vascular reactivity estimated by the reactive hyperemia-
      one of the endothelium-dependent vascular responses--in 55 healthy highlanders
      (2,200 m a.s.l.) compared to 55 healthy lowlanders matched by sex, age, body
      weight and height. Among the basic parameters of the central hemodynamics and
      myocardium contractility, there was revealed statistically significant increase
      in diastolic blood pressure, stroke volume and blood flow rate in the
      highlanders. The stroke volume increment was stipulated by rising in myocardial
      contractile activity. A mild hypertrophy of the myocardial ventricles and signs
      of pulmonary hypertension were observed in the highlanders much more often than
      in the residents of sea level. The endothelium-dependent reactive hyperemia
      simulation revealed more pronounced vasodilator responses in the highlanders. The
      peak values of the forearm blood flow, both absolute and relative, were
      significantly higher compared to those in the lowlanders. The obtained results
      allow to make a conclusion that continuous action of moderate hypoxia causes
      strengthening in cardiac pump and contractile functions, increase in endothelium
      dependent vascular reactivity and widening the vasodilator reserve due to
      increasing the production and/or release of vasodilator agents, in particular
      nitric oxide. Such widening of the vasodilator reserve might be considered as one
      of the adaptive mechanisms of cardiovascular regulation in extreme conditions.

PMID- 12226924
TI  - [Effects of ethanol on the pulmonary artery endothelium in rats].
AB  - Effects of ethanol on membrane potential and intracellular calcium concentration
      in intact endothelium of isolated pulmonary arteries were investigated. Ethanol
      evoked hyperpolarization and biphasic increase in [Ca2+]i in the endothelium due
      to both Ca2+ release from intracellular stores and Ca2+ entry from extracellular
      solution. These data allow endothelium-dependent dilation of pulmonary artery
      evoked by ethanol to be explained.

PMID- 12226925
TI  - [Effects of thermal injury on the reactivity of the neuroendocrine system].
AB  - To study reactivity of hypothalamo-hypophyseal-adrenal system to stress in
      patients with thermal skin burns we determined the content of cortisol in blood,
      chemosensitivity of glucocorticoid receptors on thrombocytes and effects of
      dexamethasone infusions on these parameters. In patients with normal reactivity
      of the organism and increased initial level of cortisol its content was shown to
      be increased by 34.1% in 2-3 hours after infusion of dexamethasone, but it
      decreased in 5-6 hours and subsequently. In patients with low initial level of
      cortisol dexamethasone caused prolongation of the hormonal response (the level of
      cortisol increased by 57.9% in 2-3 hours; by 27.1% in 5-6 hours, and by 16.9% in
      24 hours as compared to the initial level), which is a manifestation of its
      modifying effect on the reactivity of the system to stress. In these patients
      decrease in chemosensitivity of glucocorticoid receptors should be taken into
      consideration at analysis of the inflammatory reaction owing to modifying effects
      of steroid hormones on the cytokine production.

PMID- 12226926
TI  - [Changes in the activity of elastase and its inhibitors in the aorta tissue and
      blood serum of rats with streptozocin-induced diabetes].
AB  - On the model of streptozocin-induced diabetes mellitus in rats an imbalance
      between elastase and its inhibitors--alpha 1-inhibitor of proteinase and alpha 2
      macroglobulin in blood serum and aortic tissues has been established. The results
      obtained evidenced for significant imbalance of proteoclastic system towards
      enhancing the activity of proteinase and decreasing the content of its
      inhibitors. A decrease in anti-elastase activity of inhibitors in blood serum and
      aorta was due to alpha 2-macroglobulin as the most important anti-elastase
      protein in aortic tissue. Disturbances in the proteolytic system increased
      progressively at prolonging the experiment. An imbalance between elastase and its
      inhibitors at early stages of diabetes may be considered as an important
      pathogenic mechanism of such macroangiopathies as atherosclerosis and Menkeber's
      arteriosclerosis.

PMID- 12226927
TI  - [Prooxidant-antioxidant condition under increased convulsive activity].
AB  - During the clinical-biochemical research it was found that the trand's manner of
      epileptic disease in general is determined by the oxidative-antioxidant balance
      condition in the sick organism. The experimental research, made on rats, which
      were under bemegrid kindling confirmed the supposition that the pro-antioxidant
      brain balance disruption is one of the major factors in the increased convulsive
      activity development and probably plays the key role in the genesis and clinical
      revelation of epilepsy.

PMID- 12226928
TI  - [Ultrastructure of the ovaries of patients with polycystic ovarian syndrome].
AB  - Using electron microscopic techniques, we investigated bioptats of the ovaries of
      patients with polycystic ovarian syndrome after treatment with clostilbegit,
      which exerted only insignificant effects. We observed an increases in the
      intensify of proliferation of the connective tissue elements in the ovaries with
      the involvement of immunopathological processes against the background of tissue
      and circulatory hypoxia.

PMID- 12226929
TI  - [Effect of progesterone and 17beta-estradiol on proinflammatory cytokine
      costimulatory proliferative activity].
AB  - The lymphocyte proliferation is multicomponent mechanism of immune system
      reactivity. Many costimulatory factors take part in this process. Proinflammatory
      cytokines (TNF, IL-1 alpha and beta) enhance proliferation of activated
      lymphocytes. Female steroid hormones inhibit proliferation of mitogen and
      alloantigen-activated lymphocytes. The aim of this study was to investigate the
      effect of progesterone and 17 beta-estradiol on the costimulatory proliferative
      activity of proinflammatory cytokines in vitro. Female steroid hormones inhibit
      lymphocyte response to antiCD3 antibody. Progesterone had a stronger effect than
      17 beta-estradiol (64 and 13% of inhibition respectively). 17 beta-estradiol
      enhanced the TNF costimulatory effect on the lymphocyte proliferation.
      Progesterone neutralized this TNF-induced effect and reverted it (inhibition of
      lymphocyte proliferation was enhanced in the presence of TNF). We found dominant
      inhibitory effect of progesterone on the TNF costimulatory activity when
      progesterone and estrogen were added simultaneously. Progesterone and 17 beta
      estradiol downregulated costimulatory proliferative activity of IL-1 alpha or
      beta. Thus female steroid hormones had suppressive effect on the antiCD3
      stimulated lymphocyte proliferation. They downregulated costimulatory
      proliferative activity of IL-1 alpha/beta and had opposite effect on TNF
      costimulatory activity. Our results suggest possible roles female steroid
      hormones as regulators on activity of proinflammatory cytokines and their
      functions in lymphocyte proliferation.

PMID- 12226930
TI  - [Comparative analysis of various parameters of nervous system activity in
      humans].
AB  - It was established that the showing and coefficient of the nervous system power
      were connected with each other only in the conditions of determining them during
      working up of complex sensomotor information. The coefficient of the nervous
      system power determined in the conditions of working up of complex sensomotor
      information is not connected with showings of the nervous system power and that
      is why it can't be an objective showing for characteristic of the individual
      typological peculiarities of the high nervous activity.

PMID- 12226931
TI  - [Electrical responses of aortic endothelium in spontaneously hypertensive rats].
AB  - Endothelium-dependent relaxation is known to be depressed in arteries of SHR. We
      studied acetylcholine (Ach)-induced electrical responses of intact aortic
      endothelial cells from WKY rats and SHR using perforated patch-clamp method.
      Resting Em averaged--44.3 +/- 1.1 mV and -35.2 +/- 1.2 mV for WKY and SHR,
      respectively. Application of K+ free solution depolarized endothelium by 11.0 +/-
      0.7 mV and 7.5 +/- 1.3 mV (p < 0.05) for WKY and SHR, respectively, showing
      inhibition of endothelial electrogenic Na+/K+ pump in SHR. The amplitude of Ach
      induced hyperpolarization for WKY and SHR was 19 +/- 1 mV and 25 +/- 1 mV,
      respectively. However, the rate of its recovery was different within particular
      preparation taken from SHR whereas it was very similar within particular
      preparation from WKY rats, showing alterations in intercellular signaling in
      endothelium of SHR.

PMID- 12226932
TI  - Chinese cultural dimensions of death, dying, and bereavement: focus group
      findings.
AB  - The purpose of this qualitative study is to describe Chinese immigrants and
      Chinese Americans' attitudes and practices about death, dying, and bereavement.
      To this end, three focus groups were conducted with social work graduate
      students, pastors and religious leaders, and service providers working in the
      Chinese American community in New York City. The United States is becoming
      increasingly multicultural, and Chinese Americans are the most rapidly growing
      Asian American group. Findings from this study revealed that many Chinese
      attitudes and practices about death and dying are rooted in Asian cultural values
      such as filial piety, centrality of the family, and emphasis of hierarchy. In
      addition, strains of Confucianism, Buddhism, Taoism, and local folklore are
      embedded in these death attitudes and practices. Based on themes extrapolated
      from the focus groups, recommendations are delineated for service providers in
      order to implement culturally-sensitive bereavement practices.

PMID- 12226933
TI  - Ethnic similarities and differences in early elementary teachers' responses to
      tobacco prevention.
AB  - To explore ethnic differences in teachers' responses to tobacco prevention, 604
      teachers, 26.6% of whom were African American (AA), attended an initial workshop,
      and 502 completed a four-week follow-up. Class sizes were equivalent, but AA
      teachers reported teaching relatively more AA students and fewer White students.
      On initial and follow-up questionnaires, AA teachers less often reported that
      their school had a tobacco-free policy. At follow-up, both groups reported using
      tobacco prevention materials and thought that they helped students. Despite less
      organizational support, AA teachers were as positive as White teachers about
      tobacco prevention for their K-3 students.

PMID- 12226934
TI  - Health beliefs and self breast examination in black women.
AB  - The relationship between health beliefs and practice of breast self examination
      (BSE) in a sample of 179 black women, 20 to 49 years of age, was investigated.
      Health beliefs were operationalized by employing Champion's revised Health Belief
      Model Scale (1993) to collect data. Data analyses included multiple regression
      analysis to examine BSE behavior in relation to selected demographic attributes
      and health beliefs. Results indicated that health beliefs were much stronger in
      determining BSE performance for a given individual than were demographic
      characteristics. The frequency of BSE was related to increased perceived
      seriousness of breast cancer, benefits of BSE, and health motivation. Frequency
      of BSE was inversely related to perceived barriers.

PMID- 12226935
TI  - The pain locus of control orientation in a healthy sample of the Italian
      population: sociodemographic modulating factors.
AB  - We studied the pain locus of control orientation of the Italian population and
      the possible influence of the ethnocultural background and sociodemographic
      characteristics on this attributional style. An Italian version of the Pain Locus
      of Control (PLOC-It) scale was administered to 144 healthy subjects, divided into
      two ethnocultural areas (North vs South) and stratified by age (per decade 21
      60), gender (female and male) and educational level (3). The Powerful Other
      subscale had the highest mean score, followed by the Internality and Chance
      subscales. ANOVA revealed significant effects of ethnocultural area and
      educational level on Internality (F = 724, p < 0.001; F = 5.05, p < 0.05) and of
      age on Chance (F = 13.6, p < 0.001). There was a significant three-way
      interaction between area, gender and educational level on Powerful Other (F =
      3.67, p < 0.05). Further studies should be performed in populations of various
      countries to better identify the attributional styles related to the different
      cultures and the absolute sociodemographic determinants of the pain locus of
      control orientation.

PMID- 12226936
TI  - [Where does history of nursing in our countries find scientific asylum?].

PMID- 12226937
TI  - [Quality and quantitative comparison of health status during nursing care before
      and after basic kinesthesis training in a nuclear and radiotherapy clinic].
AB  - Immediately before and half a year after an introductory course into the
      principles of kinesthetic nursing the nursing team of the Clinic for Nuclear
      Medicine and Radiotherapy, City Hospital Triemli (Zurich, Switzerland), was asked
      to attend a semi-structured interview and nonverbal rating of a selection of
      important aspects of their physical and mental state during nursing. Eighteen
      persons had two interviews. The main differences in the second interview compared
      to the first one are the following: With respect to personal aims at work caring
      for the patients' well-being had fewer mentions; instead nursing was more often
      considered a process to which both sides do contribute significantly.
      Considerable improvements were found regarding to the physical contact to
      patients while caring, the team, and the nurses' general mental well-being.
      Physical benefits from the new nursing method were experienced only by part of
      the team, probably due to unplanned cancelling of kinesthetic supervision.
      Pressure due to the nurses' compassion for their patients' suffering and dying
      also was much less mentioned in the second interview, when pressure from outside,
      and lack of interdisciplinary communication and cooperation weighted more
      heavily. INTERPRETATION: Competence was already high in the team at the time of
      the first interview, but even improved by the time of the second interview. This
      is expressed by the resource-oriented patient-nurse partnership in the process of
      nursing, by team communication, as well as the heavily weighing discrepancy
      between knowledge and limited authorisation.

PMID- 12226938
TI  - [Quality of nursing diagnosis and patient satisfaction. A study of the
      correlation].
AB  - The research question was whether there exists a relationship between quality of
      nursing diagnoses in nursing documentations and patient's satisfaction with
      nursing diagnoses. The hypotheses stated that a positive relationship between
      nursing diagnosis and patient satisfaction exists; high quality of nursing
      diagnoses in the nursing documentation goes along with high patient satisfaction
      with nursing diagnoses. The sample consisted of 57 patients, their nursing
      documentations and nurses of three dermatological units of a university hospital
      in Switzerland. Nursing diagnosis was analysed from two points of view: the
      professional nursing focus and patients' focus. For this purpose, two measurement
      instruments have been developed. Three subconcepts of quality of nursing
      diagnoses and patient satisfaction were derived: interaction/personal dimension,
      patient participation and knowledge of nurses. Content validity of both
      instruments was established and the reliability coefficents of both instruments
      were rather high (.91 and .95). To test assessment objectivity, twelve raters
      analysed three nursing documentations. The tree Kappas were significant at a 5%
      level. The hypothesis was analysed by a correlational design. The main findings
      showed a significant relationship between quality of nursing diagnoses in
      documentations and patient satisfaction (tau = .18, p < or = .03). The evaluation
      of nursing diagnoses indicated effective communication between nurses and
      patients and that nurses assessed patients' situations appropriately. Patients
      satisfaction with nursing diagnoses was rather high. One of three subscales in
      both instruments yielded a significant correlation. The statistically
      significant, but low relationship suggests the need for further study.

PMID- 12226939
TI  - [At home in a strange world? Study of reality perception of a demented elderly
      patient in a nursing home: an interpretation of various viewpoints].
AB  - Only little is known about the personal experiences and feelings of demented
      elderly persons in geriatric care institutions. We conducted an intense
      qualitative case study with a 75-year old woman with Alzheimer dementia (Mrs.
      R.). Our main research method was participating observation during a period of
      almost four weeks. Information concerning the nursing staff's point of view was
      gathered by semi-structured interviews. The results indicated two different
      frames of reference. The past formed the basis for the present experience of Mrs.
      R. Her behaviour revealed a lot of signs of normality. This was especially
      evident during her daily stays in a corner seating unit of the living area. Mrs.
      R. behaved like feeling at home in that particular place. The behaviour and
      attitudes of the nursing staff were mainly determined by their perception of Mrs.
      R. as a frail and ill person. It seemed that the staff had only little knowledge
      of Mrs. R.'s biography that could have broadened their syndrome-oriented point of
      view.

PMID- 12226940
TI  - [How reliable is the Functional Independence Measure (FMI)?].
AB  - The Functional Independence Measure (FIM) is an internationally well-known
      instrument to assess patient autonomy in Activities of Daily Life. In this
      article the reliability of the instrument will be discussed by the analysis of
      data gathered on a rehabilitation ward in a Berlin hospital. The sample consists
      of 154 patients. Each patient was observed by two nurses. In the first phase of
      the project only one of these two nurses knew the patient well. In the second
      phase both nurses knew the patient. As expected, the interrater reliability
      during the second phase was higher than during the first phase of the research.
      Furthermore high correlations between the items could be computed. The internal
      consistence of the scale showed values similar to those known from literature.
      The data proved a high reliability of the instrument.

PMID- 12226941
TI  - [What measures are described in the literature for treatment of mouth problems?
      An analysis of German and English publications between 1990 and 2001].
AB  - The "mucous membrane, altered" is a frequently observed nursing diagnosis. It
      manifests itself in varying and extremely unpleasant forms of strain on the
      patient, even life-threatening complications are possible. The publications on
      mouth changes originate in the field of nursing care, however there is an
      increasing number in the medical fields of dentistry, oncology and microbiology
      as well as hygiene. A variety of remedies and instruments are suggested for
      nursing and treating patients with mouth problems. The purpose of the literary
      study was to summarize the mouth alterations to be dealt with according to each
      fundamental problem area as well as to systematize the available remedies and
      methods--which almost defy an orderly overview--according to the problem areas.

PMID- 12226943
TI  - What traits do you admire in nurse managers?

PMID- 12226942
TI  - Oncology nurse leaders identify keys to success in management.

PMID- 12226944
TI  - Critical care outreach: short-term measure or long-term solution?

PMID- 12226945
TI  - Critical care competencies.
AB  - In the absence of nationally accepted critical care competencies, each
      educational institution providing critical care programmes is forced to define
      the essential competencies necessary for practice, leading to variations in
      expected practice and the emergence of 'postcode' competencies. This research
      report aims to build upon competency activity for all areas of nursing practice
      within critical care levels 1, 2 and 3. A functional analysis to elicit core
      critical care competency statements was conducted and a modified Delphi technique
      was used to generate consensus opinion from a pan-London purposive sample of
      nurses working in critical care. The functional analysis group identified four
      competency statements and elements of competencies. Consensus agreement of 80%
      was achieved with mean agreement scores that exceed 97%. A core critical care
      competency framework was refined and developed by expert nurses drawing on their
      own experience and knowledge of critical care nursing. The framework could be
      useful to: educationalists designing competency-based curricula; critical care
      managers as a tool for recruitment and retention and for education and training
      of staff; individual critical care nurses to facilitate continuous professional
      development.

PMID- 12226946
TI  - Developing critical care skills for nurses in the ward environment: a work-based
      learning approach.
AB  - An account of collaborative working between an NHS trust and university in
      responding to the critical care agenda. An 'Introduction to Critical Care Skills'
      course initiative, which addresses the needs of nurses caring for level 1 and 2
      patients in ward areas, is discussed. Work-based learning forms the focus of
      skills development using core competencies related to a holistic approach to
      caring for patients with complex needs. A dynamic evolving process of course
      development is promoting quality care for patients and closely reflects the needs
      of those caring for acutely ill patients outside the designated critical care
      environment.

PMID- 12226947
TI  - Supporting ward staff in acute care areas: the past, the present and the future?
AB  - Clinical education for acute ward staff caring for critically ill patients has
      continued to be a strong focus for practice development. Adopting a work-based
      learning approach to empower ward staff has led to the development of a five-day
      competency-based high dependency skills course. Developing leadership potential
      and enhancing networking opportunities for nurses from within critical care and
      ward areas is essential for the realisation of the aims of Comprehensive Critical
      Care.

PMID- 12226948
TI  - The critical care outreach service and the early warning system on surgical
      wards.
AB  - The implementation and evaluation of a modified early warning system (MEWS) on
      surgical wards are described. The MEWS was found to be a useful adjunct to the
      outreach service. Early data have shown that MEWS can help direct critical
      intervention. Ward staff have benefit from both the MEWS and the outreach
      service.

PMID- 12226949
TI  - Measuring respiratory function to wean patients from non-invasive ventilation in
      a ward environment.
AB  - Non-invasive ventilation (NIV) is increasingly being introduced into various ward
      environments. NIV is usually used on wards to treat acute exacerbations of
      chronic obstructive pulmonary disease (COPD). In patients with COPD, carbon
      dioxide removal will be impaired. In critical care, arterial blood gas sampling
      remains the 'gold standard' for assessing carbon dioxide levels. Obtaining
      arterial blood gas samples in a ward environment is problematic, and potentially
      dangerous. There is currently no reliable substitute for arterial sampling to
      monitor for hypercapnia in ward areas.

PMID- 12226950
TI  - Nurses' views on withdrawing ECMO: a grounded theory study.
AB  - It was observed in practice that the withdrawal of extracorporeal membrane
      oxygenation (ECMO) was the cause of much ethical and moral discussion amongst
      nurses within the ITU where the study took place. No previous literature was
      located addressing the withdrawal of ECMO, from either a medical or nursing
      perspective. A grounded theory study was conducted to explore the experiences of
      nurses involved with the withdrawal of ECMO, focusing specifically on the
      withdrawal of this treatment from adult patients. Three major themes emerged:
      justification for withdrawal of treatment. the role of the nurse in decision
      making. the involvement of others in decision-making. The core category that
      links the three categories is 'facilitating the decision making process'
      Recommendations for future practice included, the introduction of regular formal
      meetings and debriefing, and for further research to be conducted to explore
      'corporeal anxiety' and the involvement of relatives in decision making.

PMID- 12226951
TI  - Recognized standards and recommended guidelines for the swab, instrument and
      needle count.

PMID- 12226952
TI  - Prediction of difficult intubation. A pre-assessment nurses' guide.
AB  - This article summarises a literature review which examined the best ways of
      predetermining difficult intubations for elective surgery. At Central Middlesex
      Hospital, patients are pre-assessed by nurses before intervention to ensure that
      they are fit for their operation. In the Ambulatory Care and Diagnostic Centre
      (ACAD), concern was expressed about the lack of a standardised protocol for
      nurses' assessment of the airway.

PMID- 12226953
TI  - The rise and withdrawal of droperidol.
AB  - Predicting which patients will experience postoperative nausea and vomiting is
      difficult. Prophylactic antiemetic administration has been shown to reduce
      unplanned admission after day case surgery. In published comparative studies of
      antiemetic efficacy, droperidol has been considered to be the 'gold standard'
      against which other agents are measured. The recent withdrawal of droperidol due
      to reports of cardiac arrhythmias and the potential for sudden death has left a
      vacancy for a safe and effective antiemetic. This article explores the published
      literature for alternatives to droperidol as a single dose or prophylaxis in
      patient controlled analgesia devices.

PMID- 12226954
TI  - Critical care for the surgical patient.
AB  - Dr Chris Aps has been involved, since the early 1980s, with the impact of the
      surgical patient on critical care provision. At that time, he established
      clinical techniques to lower patient dependency after cardiac surgery. This
      allowed for the postoperative management of such patients in a general recovery
      facility rather than in the formal Intensive Care Unit (ICU). This became known
      as cardiac fast-tracking and led to the development of the Overnight Intensive
      Recovery (OIR) concept.

PMID- 12226955
TI  - Using vignettes to explore how parents approach end-of-life decision making for
      terminally ill infants.
AB  - With the complexity of technologies in medical centers today, family members are
      frequently confronted with situations that require decision making on behalf of a
      loved one. Some researchers have studied the needs of decision makers directly;
      however, the reality of asking opinions at the bedside of a dying patient makes
      it a difficult issue to research directly. The vignette method has been used to
      extrapolate data by asking study participants how they would act under certain
      circumstances. This vignette-based study explores potential decision-making
      processes collected from volunteers about how family members might make decisions
      for a loved one. Ninety-four students were asked to read vignettes as if they
      were caregivers. Students were randomly assigned to one of three clinical
      scenarios describing a family member at a critical decision point. The age of the
      family member, relationship, and medical condition were manipulated in the three
      otherwise identical scenarios. The results indicated that the ranked responses to
      the categories were different in the three age-group scenarios. In the group
      simulating parent decision making for the terminally ill infant, the participants
      reported "quality of life" and "chance of survival" most frequently as to
      compared to "pain/comfort" or "family relationships" for older patients. When
      making decisions in the infant scenario, participants were twice as likely to
      express religious or spiritual criteria for their decisions and half as likely to
      express cost concerns. Among the three scenarios, participants simulating family
      decisions for infants indicated that different caregiving values may apply. They
      were even more likely than the others to choose mechanical ventilation as an
      option when the prognosis is extremely poor. All family members making decisions
      for a loved one, regardless of age or relationship, need supportive assistance
      from nurses; however, pediatric nurses who develop relationships with parents of
      terminally ill infants especially need to understand their values in making
      decisions.

PMID- 12226956
TI  - Greek nurse and physician grief as a result of caring for children dying of
      cancer.
AB  - This descriptive study explored and compared the grief responses and experiences
      of Greek physicians and nurses who provide care to children dying of cancer.
      Interviews were conducted with 14 oncologists and 16 pediatric oncology nurses.
      Data were subjected to a combination of qualitative and quantitative methods of
      analysis. For both groups, the dying process and death of children were highly
      stressful experiences and triggered a grieving process. Differences, however,
      were observed in terms of the way these two groups (a) perceived the loss of the
      child and (b) expressed or avoided their grief. It became apparent that health
      professionals' grieving process was affected by how they perceived their role,
      interventions, and contribution in the care of the dying child, which in turn was
      influenced by the social and cultural context in which care is provided to
      children with cancer. Findings suggest that despite the distress caused by
      children's death, both nurses and physicians identified specific rewards they
      reaped from caring for children who are terminally ill.

PMID- 12226958
TI  - The changing dynamics of pediatric pre-licensure education.
AB  - Pediatric nursing educators in both academic and practice settings have expressed
      significant concerns regarding the decreased amount of pediatric content and
      clinical experiences within pre-licensure educational programs. In addition, data
      gathered at a national conference of pediatric staff nurses, researchers,
      educators and administrators indicated there are concerns about the quality and
      quantity of future pediatric-nurse educators, the availability of acute care
      learning experiences, as well as the changing nature of today's nursing students
      and children's families.

PMID- 12226957
TI  - ART is the heART: a palette of possibilities for hospice care.
AB  - Comprehensive hospice care for children who are dying or dealing with the death
      of a parent, sibling, or other family member must include psychologic, emotional,
      and spiritual support. Increasingly, the arts are being recognized as a powerful
      tool for this support. In 1999, WVSA arts connection, a community-based, arts and
      education, non-profit organization in Washington, DC, developed and launched a
      unique arts-in-health care program, ART is the heART. The program trains and
      brings artists to children and families in home or hospice care. Through ART is
      the heART, children learn to use the arts as a healthy and effective coping
      strategy. The program is now being replicated in other communities across
      America.

PMID- 12226959
TI  - A systems approach to delivering clinical preventive services.

PMID- 12226960
TI  - Promoting positive parenting: an annotated bibliography.
AB  - Positive parenting is built on respect for children and helps develop self
      esteem, inner discipline, self-confidence, responsibility, and resourcefulness.
      Positive parenting is also good for parents: parents feel good about parenting
      well. It builds a sense of dignity. Positive parenting can be learned.
      Understanding normal development is a first step, so that parents can distinguish
      common behaviors in a stage of development from "problems." Central to positive
      parenting is developing thoughtful approaches to child guidance that can be used
      in place of anger, manipulation, punishment, and rewards. Support for developing
      creative and loving approaches to meet special parenting challenges, such as
      temperament, disabilities, separation and loss, and adoption, is sometimes
      necessary as well. This annotated bibliography offers resources to professionals
      helping parents and to parents wishing to develop positive parenting skills.

PMID- 12226961
TI  - A wheeze by any other name?

PMID- 12226962
TI  - Pediatric management problems.

PMID- 12226963
TI  - Early predictors of poor coping outcomes in children following intensive care
      hospitalization and stressful medical encounters.

PMID- 12226964
TI  - School nurses: what it was and what it is.

PMID- 12226965
TI  - Children's adherence to recommended asthma self-management.
AB  - PURPOSE: Adherence to peak expiratory flow rate monitoring by children with
      asthma was evaluated, and a behavioral strategy to enhance adherence to daily
      monitoring was tested. DESIGN AND METHODS: Forty-two 7- through 11-year-old
      children with persistent asthma were recruited into a 5-week randomized,
      controlled clinical trial. Adherence data were collected electronically by
      PeakLog and the self-report Asthma Diary. RESULTS: Adherence declined over time.
      At week 5, intervention group adherence (Median = 79%) was higher than the usual
      care group adherence (Median = 64%), but the difference was not statistically
      significant. The effect size did suggest that differences between groups were
      present. CONCLUSIONS: Even small improvements in adherence to asthma treatment
      may be clinically significant in light of the alarming increases in asthma
      morbidity and mortality. Contingency management shows promise for improving
      adherence outcomes. Future research should engage larger sample sizes and
      increase the number and intensity of sessions to teach behavioral strategies.

PMID- 12226966
TI  - The Health Insurance Portability and Accountability Act and adolescents.
AB  - Adolescents are one of the most at-risk and underinsured age groups (Centers for
      Disease Control and Prevention [CDC], 2000). The new Health Insurance Portability
      and Accountability Act (HIPAA) regulations will affect all aspects of the health
      care delivery system and are designed to protect consumers. The adolescent
      consumer, however, may not fare so well with the new regulations. Providers
      delivering care to adolescents have often been involved with regulations that
      hampered their ability to deliver care to this age group.

PMID- 12226968
TI  - [Results of Nd-YAG laser effects in manifest exudative reaction after
      implantation of intraocular lens].
AB  - Thirteen patients (16 eyes) with artiphakia developed exudative reaction with
      formation of fibrinous conglomeration occupying up to 2/3 of the anterior chamber
      volume. Noninvasive YAG laser exposure was carried out to destroy the
      conglomeration. Complete cleansing of the anterior chamber and IOL was attained
      in 2-7 sessions (energy 0.8-8.0 mJ, up to 100 pulses). The difference in the
      periods between relapses and the number of relapses decreased after each
      exacerbation. YAG laser exposure destroyed the exudative conglomeration and
      stimulated its lysis with the minimum complications. Hence, Nd:YAG laser exposure
      is a promising method of choice.

PMID- 12226967
TI  - [Surgical strategy of treatment of severe and extremely severe eye burns. I].
AB  - A total of 112 patients with severe and extremely severe burns of the eyes were
      treated. The author proves that one of the main causes of unsatisfactory results
      is the absence of clearly defined criteria for the choice of surgical strategy
      during the early period. Based on the classification of interventions, the author
      suggests an algorithm of early surgical treatment of eye burns.

PMID- 12226969
TI  - [Laser magnetotherapy after cataract extraction with implantation of intraocular
      lens].
AB  - Effects of low-intensive laser and alternating magnetic field on the course of
      the postoperative period were studied in patients with exudative reaction after
      extracapsular cataract extraction with implantation of intraocular lens (IOL).
      The results are analyzed for 148 eyes with early exudative reaction after IOL
      implantation (136 patients aged 42-75 years). The patients were observed for up
      to 6 months. The treatment efficiency was evaluated by the clinical picture of
      inflammatory reaction, visual acuity, and results of biochemical analysis of the
      lacrimal fluid (the ratio of lipid peroxidation products to antioxidants in cell
      membrane). The course of the postoperative period was more benign and recovery
      sooner in patients of the main group in comparison with the control.

PMID- 12226971
TI  - [Relationship between constitutional type of systemic hemodynamics and formation
      of peripheral vitreo-chorioretinal dystrophies during pregnancy].
AB  - Dynamic observations of 86 pregnant women with peripheral vitreochorioretinal
      dystrophies (PVCRD) (121 eyes) showed that the condition progressed during
      pregnancy in 33.8% cases. Decrease of ocular hemodynamics and scleral rigidity
      were characteristic of pregnancy, being particularly pronounced in OPH gestosis.
      The highest incidence of PVCRD progress was observed in pregnant women with the
      hypokinetic type of systemic hemodynamics, being 30% in normal pregnancy and
      reaching 48% in OPH gestosis vs. 8.3 and 16.6 and 16.6 and 22.7% in the hyper-
      and eukinetic types, respectively.

PMID- 12226970
TI  - [Epithelial complications of sub-flap intrastromal photo-kerato ablation for
      correction of ametropia: causes, therapy, prophylaxis].
AB  - The causes of epithelial complications are evaluated from clinical viewpoint and
      approaches to their elimination in laser operations are developed. The study
      included analysis of 3227 intrastromal ablation operations performed by the LASIK
      and REIK methods in 1725 patients with myopia (spheroequivalent -6.47 +/- 2.23
      diopters) and hypermetropia (spheroequivalent +4.57 +/- 1.88 diopters). Laser
      keratoablation was carried out on an EC 5000 device (Nidek, Japan). Lamellar
      keratomileusis was carried out with a Hansatome Chiron Vision 230 HT-TM
      microkeratotome (USA). The incidence of epithelial complications was 5.2%.
      Intraoperative complications occurred in 3.2% cases. Corneal erosions of 1 x 3 mm
      were responsible for 51.2% complications, extensive erosions for 18.4%,
      horizontal ruptures of the epithelium for 22.4%, and stretching of epithelial
      plast for 9.8% complications. Other complications were epitheliopathy (6 cases),
      growth of epithelium under corneal flap (0.7%), and "dry islets" in the
      epithelium (22%). The probable causes of epithelial complications were
      microkeratotome design, toxic effects of anesthetics, congenital desmosomopathy,
      and insufficient adaptation of corneal flap. Prevention of complications should
      consist in additional protection of the epithelium before and after the
      operation. The protection can be realized by using low-toxic antibiotics,
      viscoelastic liquids during performance of the lamellar section of the cornea,
      soft contact lenses, tear substitutes, and lacrimal film stabilizers during the
      early postoperative period.

PMID- 12226972
TI  - [Electroencephalography in the diagnosis and prognosis of post-traumatic
      uveitis].
AB  - Changes in the brain biopotentials during early and remote periods after
      perforating wounds of the eyes were for the first time investigated in 55
      patients with posttraumatic uveitis (PTU). Increased alpha-rhythmic activity of
      the brain was detected, its location and intensity depending on the severity of
      injury and PTU and course of PTU. The possibility of predicting the outcome of
      uveitis was demonstrated and diagnostic value of the method in evaluation of its
      severity was proven. In favorable outcomes of PTU, alpha-rhythm intensified in
      the anterior compartments of the brain. In severe uveitis and risk of sympathetic
      inflammation, brain activity increased in the posterior compartments presenting
      as sharp waves, being pronounced in both hemispheres or on the intact eye side.

PMID- 12226973
TI  - [Theoretical validation of local express auto-cytokine therapy].
AB  - Theoretical validation for local express autocytokine therapy (LEACKT), used in
      recent years with good results for the treatment of viral and nonviral diseases
      of the eyes, is provided. In vitro experiments showed that autologous cytokine
      complex appearing after stimulation of patient's peripheral whole blood with
      poludan (polyA:polyY complex, 200 micrograms) includes all three interferon types
      (alpha, beta, and gamma) and interleukin-8 (IL-8) and tumor necrosis factor
      (TNF). It was shown for the first time that poludan stimulated the production of
      IL-8, the main chemotactic cytokine inducing chemotaxis, neutrophil activation,
      angiogenesis stimulation, and regeneration. This was not paralleled by an
      increase in the production of TNF, the key mediator of inflammation, whose level
      in whole blood did not increase. Addition of poludan to cell culture led to a 2
      fold decrease of lymphocyte apoptosis in comparison with that after treatment
      with dexamethasone alone. The results of experiments indicate that LEACKT with
      poludan is characterized by pronounced antiinflammatory, interferonogenic,
      regeneratory, and antiapoptosis effects in various diseases of the anterior
      segment of the eye and is a simple and safe method.

PMID- 12226974
TI  - [Clinical and pathogenetic significance of Proteus mirabilis antibodies in
      uveitis associated with joint lesions in children and adolescents].
AB  - Immunological studies in 95 children with uveitis associated with juvenile
      chronic arthritis revealed infection with Proteus mirabilis in 14.7% cases,
      mainly in cases with reactive arthritis and juvenile rheumatoid arthritis (JRA).
      A clear-cut relationship between P. mirabilis infection and severity of the
      disease was detected. In 85% children infected with P. mirabilis uveitis was
      associated with a rapid decrease of ocular functions and development of
      complications, one of the most frequent of which was vitreous fibrosis, generally
      not typical of classical rheumatoid uveitis. Antibodies to P. mirabilis were
      detected in 72.2% children with positive antinuclear factor, a marker of
      ophthalmoarticular rheumatic diseases. The pathogenetic significance of P.
      mirabilis in uveitis associated with articular involvement deserves further
      investigation, but even now the detection of P. mirabilis can be used as a marker
      of uveitis exacerbations and severity.

PMID- 12226975
TI  - [Revascularization decompression of the optic nerve: a new surgery of the optic
      nerve in progressive glaucomatous optic neuropathy].
AB  - A new operation on the optic nerve scleral canal, revascularization compression
      of the optic nerve, was carried out in 21 patients (21 eyes) in order to improve
      the visual functions and stabilize the glaucomatous process. The operation
      combines the advantages of decompression of the optic nerve by dissection of the
      posterior scleral ring with creation of an additional source of blood supply to
      the optic nerve from the myovascular bundle of the internal rectal muscle. Good
      functional effect and notable improvement of hemoperfusion of the optic nerve and
      retina were attained (period of observation up to 2 years). The degree of visual
      field extension correlated with the degree of increase in hemoperfusion values.
      Comparative analysis showed a higher functional efficiency of revascularization
      decompression of the optic nerve in comparison with optic nerve decompression,
      which is due to a more essential improvement of ocular hemoperfusion.

PMID- 12226976
TI  - [Changes in oxidative processes in the anterior segment of the eye in patients
      with keratoconus].
AB  - Biochemical parameters of the tears, reflecting oxidative processes in the eyes,
      were analyzed in 79 patients (146 eyes) aged 19-42 years with progressive and
      acute keratocone and with long remission of the disease. The data indicate
      disorders in oxidative processes with predominance of aerobic oxidation over
      anaerobic in the anterior segment of the eye. Evaluation of lipid peroxidation
      and antioxidant enzymes showed predominance of prooxidant processes over oxidant.
      These disorders are related in keratocone and differ in progressive, acute
      condition, and remission. The greatest changes in the lacrimal oxidative
      processes are observed during the disease progress and even more so in acute
      disease. The detected changes in the lacrimal biochemistry in patients with
      keratocone can be regarded as an important mechanism underlying the dystrophic
      processes in the cornea.

PMID- 12226978
TI  - [Effects of immunization on proteinase-inhibitor balance in the lacrimal fluid
      and blood serum in alkaline burns of the cornea (an experimental study)].
AB  - Proteinase-inhibitor balance in the lacrimal fluid in eye burns was studied in
      rabbits with modified and intact immune status. Stimulation of the immune system
      was induced by complete Freund's adjuvant. Clinical picture of the disease was
      studied in parallel. Immunization accelerated the local adaptive and defense
      reaction of the proteolytic enzymes and their inhibitors, which was paralleled by
      a more benign course of burn disease of the eyes, in comparison with that in non
      immunized animals.

PMID- 12226977
TI  - [Characteristics of pharmacodynamics of drugs after excimer laser surgery (an
      experimental study)].
AB  - Pharmacodynamics of dexamethasone, fluoromethanol, sodium diclofenak, and
      tobramicin after photorefraction keratectomy (PRK) and intrastromal laser
      keratectomy (ILK) was studied in rabbits. Eximer laser operations modulated the
      barrier functions of the cornea. The highest concentrations of drugs in anterior
      chamber humor during the first 20 min after instillations was observed after ILK
      in comparison with the control (intact cornea). The highest coefficient of
      effective drug diffusion through the cornea was observed after PRK in comparison
      with ILK. The drug efficiency was higher after ILK than after PRK, which is seen
      from the maximum concentrations of drugs entering the cornea immediately after
      instillation and prolongation of the drug effect due to its decelerated diffusion
      through the cornea.

PMID- 12226979
TI  - [Psychological characteristics of patients with primary open-angle glaucoma].
AB  - Psychological disorders of different severity are observed in 89.7% patients with
      primary open-angle glaucoma. They can be detected both clinically and by
      psychological tests. The psychological status and personality characteristics of
      patients with glaucoma were evaluated by SMOL method and Cattel's 16 Personality
      Factors. Signs of psychological disadaptation are more pronounced in patients
      with the initial and well-developed stages of the disease and in those not
      treated surgically. The duration of the disease does not affect the psychological
      characteristics of patients with primary open-angle glaucoma. Consideration for
      the psychological factor is obligatory in combined therapy of patients with
      glaucoma.

PMID- 12226980
TI  - [Possibilities of improving vision of poorly sighted patients by means of a
      diaphragm].
AB  - The possibility of using diaphragming means for improving the vision of poorly
      sighted patients is discussed. A total of 279 patients (514 eyes) aged 6-82 years
      were examined, 118 (42.3%) of these with ocular diseases. Comparative analysis of
      the time course of visual acuity was carried out in patients using diaphragming
      means, optimal eyeglasses, and both. Eyeglasses are preferable for the majority
      of patients with poor vision, as they allow a higher visual acuity than
      diaphragming eyeglasses. Diaphragming means are more effective in patients with
      opaque optic media of the eyes with slight refraction disorders. A diaphragming
      racket is suggested for utilization of the useful characteristics of the
      diaphragm; it can be combined with eyeglass correction of ametropia. A group of
      patients was distinguished, for whom the combination of these two types of
      correction is the most effective: patients with corneal dystrophy, involution
      cataract, retinopathy neonatorum, aphakia, high complicated myopia, and diabetic
      retinopathy. In addition, the diaphragming racket is recommended for use during
      consultations for more accurate evaluation of the correction of ametropia and the
      intactness of the retinal macular zone in patients with opaque optic media of the
      eye.

PMID- 12226981
TI  - [A case with spontaneous adhesion of the retina in the cicatricial stage of
      retinopathy of prematurity].

PMID- 12226982
TI  - [Clinical picture of eye involvement in opisthorchiasis].

PMID- 12226983
TI  - [Secondary bacterial infection of the cornea in intensive care unit].

PMID- 12226984
TI  - [Congenital corneal opacities: current problems in differential diagnosis and
      treatment strategy].

PMID- 12226985
TI  - [Arterial pressure in the orbital artery and eye perfusion in patients with
      different stages of primary open-angle glaucoma].
AB  - A total of 902 patients aged 40-82 years (1804 eyes) with primary open-angle
      glaucoma (POAG) with different stages of the disease and different intraocular
      pressure (IOP) and systemic arterial pressure (AP) 105-170 mm Hg were examined.
      Control group consisted of 340 age-matched normal subjects (680 eyes) with the
      same values of AP. Systemic AP affected the mean dynamic and perfusion pressure
      (Pm.ophth. and Pperf.) in both normal subjects and patients with POAG. In
      addition, both parameters in POAG patients depended on IOP and duration of the
      glaucomatous process. An increase of IOP was paralleled by a compensatory
      increase of Pm.ophth., but the higher IOP (an increase within the b-c interval),
      the less pronounced the increase of Pm.ophth., particularly in patients with well
      developed and advanced stages. A progressive decrease of Pperf. was observed,
      which was related to high IOP and duration of the glaucomatous process.

PMID- 12226986
TI  - [Current concepts of the etiology and pathogenesis of keratoconus].

PMID- 12226987
TI  - [Para-aminobenzoic acid and prospects of its use in ophthalmology].

PMID- 12226988
TI  - [Lipid peroxidation and antioxidant defense in eye diseases].

PMID- 12226989
TI  - [Visocontrastometry as one of diagnostic criteria for early detection of glaucoma
      and evaluation of stabilization of glaucomatous process].
AB  - The relationship between contrast-frequency characteristics of the eye, on the
      one hand, and visual acuity and peripheral field, photosensitivity in the central
      visual field, ophthalmic tone, and area of the optic disk neuroretinal zonule, on
      the other, was for the first time evaluated by regression-correlation analysis.
      Videograms averaged for groups with consideration for glaucoma stage and changes
      in visual acuity in each group were compared. The sensitivity and specificity of
      visocontrastometry for early detection of glaucoma and evaluation of
      stabilization of the glaucomatous process were assessed. Based on the results,
      the author formulated her suggestions supplementing the classification of primary
      glaucoma currently used in Russia.

PMID- 12226990
TI  - [Drug correction of hypoxia aftereffects in patients with toxic coma caused by
      acute neurotropic poisoning].
AB  - Seventy-eight patients with acute neurotropic poisoning (soporifics,
      neuroleptics, antidepressants, ethanol and its surrogates, narcotics) were
      examined and treated. Study of the pathogenesis of hypoxic injuries in acute
      neurotropic poisoning demonstrated the efficiency of using Perfluorane, an
      infusion solution with oxygen transporting functions, and Cytoflavine, a
      substrate antihypoxant, for correction of the detected disorders.

PMID- 12226991
TI  - [Time course of toxic hypoxic encephalopathy during combined therapy including
      hyperbaric oxygenation].
AB  - The mechanisms of action of hyperbaric oxygenation (HBO) in toxic hypoxic
      encephalopathy (THE) were studied using clinical psychopathological examinations,
      functional and laboratory tests in 268 patients with THE treated by a therapeutic
      complex including HBO and 75 patients with THE treated routinely (controls). The
      earliest possible addition of HBO to a complex of treatment of THE patients led
      to involution of signs of brain edema shown by computer tomography (CT) and
      improvement of its functional activity, while in patients exposed to HBO later
      the psychoorganic symptoms and CT signs of cerebral ischemia did not disappear.
      Detoxifying, neuroimmunomodulating, and neuroimmunostimulating effects of HBO in
      THE were demonstrated. Early HBO treatment decreased the dysfunction of various
      compartments of the brain characteristic of THE. The technology of HBO developed
      by the authors prevented the development of socially dysadapting
      psychoneurological disorders and reduced the mortality of THE patients.

PMID- 12226992
TI  - [Disorders of lipid peroxidation processes and blood antioxidant system in acute
      poisoning with psychotropic drugs].
AB  - Study of lipid peroxidation (LPO) processes and antioxidant defense (AOD) system
      of the blood in 96 patients with psychotropic drug poisoning of different
      severity showed disorders in the LPO/AOD system irrespective of the initial level
      of chemical injury. These disorders are characterized by imbalance in the ratio
      of LPO and AOD components. The severity and direction of these disorders depend
      on the severity of intoxication and poison exposure in the body before treatment
      measures, which dictates correction of these disorders with consideration for
      individual LPO and AOD parameters.

PMID- 12226993
TI  - [Possibilities of fiber bronchoscopy in complex diagnosis and treatment of
      inhalation injuries of the tracheobronchial tree].
AB  - The treatment of patients with burn injuries of the tracheobronchial tree is a
      pressing problem today, because of rather high prevalence of this injury and high
      mortality (90%). Clinical signs during the first 24 h do not allow evaluating the
      severity of the injury. Based on analysis of case histories of 24 patients, the
      authors sum up results of complex examinations including fibrobronchoscopy,
      microbiological, and histological studies. Fibrobronchoscopy precisely showed the
      degree and extension of airway involvement in burn injuries, while accessory
      microbiological and histological studies help timely predict the development of
      pyoseptic complications. Endoscopic methods of therapy promote a more rapid
      reduction of inflammation and healing of erosive ulcerative involvement of the
      tracheobronchial mucosa.

PMID- 12226994
TI  - [Role of abnormalities of the lung surfactant system in the development of
      respiratory failure in critical states caused by acute neurotoxic poisoning].
AB  - Clinical data on the surfactant system of the lungs during poisoning with
      neurotoxic toxins are presented and approaches to drug correction of lung system
      disorders in severe intoxication with neurotoxic agents are offered.

PMID- 12226995
TI  - [Toxicity of mushrooms Paxillus involutus and Paxillus atrotomentosus].
AB  - Thirty-eight patients with mushroom (Paxillus involutus and Paxillus
      atrotomentosus) poisoning were treated. Slight poisoning (acute gastroenteritis)
      was diagnosed in 17 patients, medium-severe in 13, severe in 6, and extremely
      severe in 2 patients. Changes in the LPO-AOD system correlated with the severity
      of hepatorenal involvement. The treatment included hepatotropic therapy; patients
      with acute renal failure were treated by hemodialysis. Paxillus mushrooms induced
      functional evacuatory disorders in the small intestine. Eleven patients with
      adhesions in the abdominal cavity developed ileus. Two patients died: a man aged
      26 years after eating fried (not boiled) mushrooms and a woman aged 76 years with
      ileus with symptoms of multiple organ dysfunction. The rest patients were
      discharged from hospital in satisfactory condition. Clinical course of poisoning
      with Paxillus mushrooms is discussed.

PMID- 12226996
TI  - [Effect of sodium hypochlorite on neuroregulatory systems in acute psychotropic
      drug poisoning].
AB  - The effect of sodium hypochlorite (SHC) on neuroregulatory systems was studied in
      patients with acute poisoning with psychotropic drugs infused intravenously as
      components of infusion therapy. Infusion therapy alone or in complex with SHC
      does not affect the cholinergic system of the organism. The corrective effect of
      SHC on the sympathetic, serotonin- and histaminergic systems was more pronounced
      in comparison with infusion therapy and was the most expressed on day 2 after the
      treatment.

PMID- 12226997
TI  - [Morphological aspects of diagnosis of acute opiate poisoning].
AB  - Clinical anatomical analysis, forensic chemical, morphological, bacteriological,
      and immunological investigations of material from 62 subjects dead from acute
      poisoning with opiates before hospitalization (31 cases) and in hospital (31
      cases) were carried out. Organ and tissue lesions typical of opiate poisoning
      were detected. The outcome of acute poisoning with opiates is largely determined
      by severe dystrophic and inflammatory processes in organs and tissues, typical of
      narcomaniacs.

PMID- 12226998
TI  - [Information stress of the anesthesiologist and intensive care specialist].
AB  - This paper discusses the results of examinations of 87 anesthesiologists and
      intensive care specialists, aimed at elucidation of the effects of stress factors
      on their work, analyzes various aspects of stress in these specialists. The
      resistance of a physician to psychological (information) stress is determined by
      biological, social, and psychological factors. The desirability of creating a
      universal system of psychological monitoring of anesthesiologists and intensive
      care specialists is validated.

PMID- 12226999
TI  - [Peritoneal dialysis in the newborn and infants after radical correction of
      complex congenital heart defects].
AB  - The efficiency of peritoneal dialysis (PD) was evaluated in newborns and infants
      with multiple organ dysfunction (MOD) after cardiosurgery. In 1996-2001 at A. N.
      Bakulev Cardiovascular Surgery Center, Russian Academy of Medical Sciences, PD
      was used as permanent renal replacement therapy (RRT) in 19 newborns and infants
      aged under 1 year after radical correction of congenital heart diseases. The mean
      age of infants was 6.2 +/- 4.3 months, body weight 6.1 +/- 1.7 kg. Radical
      correction of congenital heart diseases was carried out in all patients. The
      immediate postoperative period was complicated by MOD in all patients. Pronounced
      cardiac, respiratory, and renal insufficiency was observed in all cases. The main
      indication for the beginning of PD was oligouria, hypervolemia, edematous
      syndrome with progressive cardiorespiratory insufficiency. Multiple-modality
      intensive care including PD resulted in positive changes in the clinical status
      of infants by days 4-5 of PD: hemodynamic values, gaseous exchange function of
      the lungs, and laboratory values improved. Hence, PD as an RRT method in newborns
      and infants subjected to radical cardiosurgery proved to be effective in the
      complex of intensive care measures for MOD. This sufficiently simple method,
      requiring no expensive equipment, adequately corrects hyperhydration and
      hypervolemia, metabolic and electrolyte disorders, and other MOD symptoms in
      newborns and infants.

PMID- 12227000
TI  - [A present-day variant of intermitttent replacement renal therapy in patients
      with multiple organ failure after cardiovascular surgery].
AB  - The efficiency of "semi-prolonged" replacement renal therapy (RRT) was assessed
      in patients with multiple organ dysfunction (MOD) after cardiovascular surgery.
      The results of semiprolonged RRT are analyzed in 65 patients (36-69 years, mean
      age 52.4 +/- 15.7 years, body weight 57-105 kg, mean 79.4 +/- 21.6 kg) operated
      on at A. N. Bakulev Cardiovascular Surgery Center, Russian Academy of Medical
      Sciences. Bicarbonate hemodialysis (BHD) was carried out in 50 patients, on-line
      hemodiafiltration (HDF) in the rest patients. Interventions on the heart and
      vessels of different complexity were carried out. The results indicate that
      semiprolonged SRT in complex with intensive care measures notably reduced the
      mortality of patients with MOD and improved the survival rate in this category of
      patients. Semiprolonged RRT is an effective method, which can and should be used
      in critical patients. This method meets all the requirements to modern RRT and
      ensures adequate filtration of nitrous metabolism products, corrects water
      electrolyte and acid base balance, allows infusion/transfusion therapy and
      parenteral nutrition, and has no negative impact on the hemodynamic values, which
      is particularly important after cardiovascular interventions.

PMID- 12227001
TI  - [Effectiveness of plasmapheresis and its modifications in the treatment of
      cardiosurgical patients].
AB  - The efficiency of plasmapheresis in the treatment of infectious complications and
      multiple organ dysfunctions was evaluated in 66 patients after heart surgery.
      Early plasmapheresis attenuated the cytokine-related systemic inflammatory
      response and organ damage. The optimal use of plasmapheresis modifications
      (membrane plasma filtration, plasma carboperfusion, cryoapheresis) improved the
      clinical outcomes.

PMID- 12227002
TI  - [Renal replacement therapy in acute infectious renal insufficiency].
AB  - A modern view on renal failure in patients with infectious diseases is presented
      and possibilities of various methods of renal replacement therapy are evaluated.
      The authors emphasize the obligatory combination of etiotropic and pathogenetic
      therapy. A clinical case is presented: a patient with tropical and 3-day malaria
      was effectively treated by high-flow intermittent hemofiltration.

PMID- 12227003
TI  - [Integrated hemodynamic response to hemofiltration and peritoneal dialysis in
      patients with acute renal failure].
AB  - Central hemodynamics was studied by integral polyrheography in 24 patients with
      acute renal failure (ARF) during hemofiltration (HF) and in 18 patients with ARF
      during peritoneal dialysis. All central hemodynamic parameters improved by the
      end of HF. However stroke volume decreased by 26.6%, stroke index by 24.4%,
      minute volume by 25.7%, and cardiac index by 24.8% as early as at the moment of
      extracorporeal contour filling. This was paralleled by an increase of total
      peripheral vascular resistance from 1321 +/- 124 to 1586 +/- 106 din/(cm*c-5) (by
      16.7%). Hence, clear-cut signs of centralization of circulation were seen during
      the initial period of HF in patients with ARF. Peritoneal dialysis did not lead
      to centralization of circulation in patients with ARF; moreover, minute heart
      volume increased by 9% during some stages of the procedure, stroke volume
      increased significantly (p < 0.05), other parameters increased, but total
      peripheral vascular resistance was virtually unchanged. After removal of dialysis
      solution from the abdominal cavity all hemodynamic parameters returned to the
      initial values. Hence, both hemofiltration and peritoneal dialysis ameliorate the
      central hemodynamics. However peritoneal dialysis does not involve even temporary
      centralization of circulation, which has a positive impact on the course of acute
      tubular necrosis.

PMID- 12227004
TI  - [Systemic hemodynamics in constant hemofiltration in patients with septic shock].
AB  - Hemodiafiltration (HDF) is a method of pathogenetic therapy for the systemic
      inflammatory response syndrome in patients with sepsis and shock irrespective of
      renal failure. Systemic hemodynamics was examined in 18 patients with septic
      shock treated by HDF (2 groups). HDF was associated with stabilization of
      systemic hemodynamics in 50% patients (cardiac index, total peripheral
      resistance, index of the left heart work increased and the number of heart beats,
      central venous pressure, mean pressure in the pulmonary artery, pulmonary
      capillary wedging pressure decreased, oxygen consumption index increased, etc.),
      which allowed a reduction of the initial dopamine and norepinephrine doses 3-fold
      and lower by the end of days 3-4 of HDF treatment. An opposite tendency was
      observed in group 2 (refractory shock). Despite high (72.2%) mortality which was
      mainly caused by the progress of multiple organ dysfunction or untimely surgical
      intervention, it is obvious that HDF created conditions for surviving the
      critical period of disease in patients with progressive sepsis.

PMID- 12227006
TI  - [Comparative evaluation of enoxaparin and non-fractionated heparin in patients
      with pancreonecrosis].
AB  - Hemostasis dysfunction plays an important role in the pathogenesis of
      pancreonecrosis. Platelet and clotting factor activation in the presence of
      hyperfibrinogenemia and suppressed fibrinolysis develop during the stage of
      pyonecrotic complications, which provokes microcirculatory disorders, the main
      cause of pancreonecrosis progress. Treatment with nonfractionated heparin (NFH)
      for prevention of blood clotting does not prevent the development of the DIC
      syndrome, as, despite its anticoagulation activity, the drug possesses
      proaggregation effects and is devoid of the profibrinolytic effect. Laboratory
      signs of the DIC syndrome were detected in the majority of patients treated with
      NFH (decreased level of antithrombin III, prothrombin index, and fibrinolysis
      suppression). Blood clotting prevention with clexane (enoxaparin) was effective,
      as this drug did not stimulate platelet aggregation and promoted the maximum
      realization of fibrinolysis, the defense function of the hemostasis system. The
      absence of microclots in capillaries of patients treated with clexane manifested
      by intensification of tissue perfusion and hence, more effective draining of
      destruction zone. Increase of tissue perfusion outside the destruction zone
      prevented the dissemination of necrosis and disease progress, i.e. promoted the
      elimination of one of the most important mechanisms of pancreonecrosis
      pathogenesis.

PMID- 12227005
TI  - [Extracorporeal detoxication in combined therapy of pancreonecrosis].
AB  - Extracorporeal detoxication methods (hemofiltration, discrete exchange and
      filtration plasmapheresis) were added to intensive care complexes for 53 patients
      with pancreonecrosis. Peritonitis with multiple organ dysfunction was diagnosed
      in all patients. The severity of intoxication, central hemodynamic parameters,
      blood gaseous composition were evaluated in the monitoring regimen. Oxygen
      transport and consumption were estimated. Pancreonecrosis was paralleled by
      severe endogenous intoxication. Hemofiltration led to a stable decrease in the
      level of pancreatogenic toxicosis in the majority of patients. Combination of
      hemofiltration and plasmapheresis led to a more rapid and effective elimination
      of creatinine, bilirubin, and amylase without essential changes in the
      electrolyte composition. Clinical symptoms of acute respiratory and cardiac
      insufficiency decreased, central hemodynamics and oxygen transporting function of
      the blood improved. Combination of hemofiltration and plasmapheresis mutually
      potentiated the positive effects of both methods and extended the potentialities
      of filtration methods in replacement of organ dysfunctions in multiple organ
      dysfunction.

PMID- 12227007
TI  - [Selective detoxication of the portal vein blood in toxic hepatopathy in patients
      with peritonitis].
AB  - Selective detoxication of the blood from the portal vein was carried out in 31
      patients with peritonitis complicated by multiple organ dysfunction including
      toxic hepatopathy. Selective extracorporeal detoxication of the blood from the
      portal vein possesses notable regional hemodynamic advantages in comparison with
      other variants of vascular approaches and essentially improves the transhepatic
      bloodflow. The authors emphasize that bifiltration cascade exchange
      portoplasmapheresis is a method of choice in severe toxic hepatopathy in patients
      with peritonitis. They recommend alternating bifiltration cascade exchange
      portoplasmapheresis with portohemofiltration in patients with toxic
      hepatonephropathy.

PMID- 12227008
TI  - [Blood purification in sepsis: a reasonable hypothesis or waste of time?].

PMID- 12227009
TI  - [Features of diagnosis and treatment of endotoxicosis syndrome in acute chemical
      poisoning].
AB  - Experience gained in the treatment of more than 750 patients with acute poisoning
      complicated by endotoxicosis showed that the entire complex of typical changes in
      endotoxicosis markers and homeostasis parameters (hematological, immunological,
      hemorheological, LPO/AOD) should be taken into consideration during the
      diagnostic studies. These shifts should be timely corrected by the basic efferent
      methods of artificial detoxication (hemosorption, hemodiafiltration,
      hemofiltration) with obligatory physio- and chemohemotherapy (laser-UV
      hemotherapy, infusion of sodium hypochlorite).

PMID- 12227010
TI  - [Vegetarian diet in treating elderly patients with ischemic heart disease
      (clinico-hemodynamic, biochemical, and hemorheological effects)].
AB  - The inclusion of balanced antiatherogenis of vegetarian diet in a complex of
      therapeutical means of the patients of ischemic heart disease in elderly age
      (average age 72.3 years) promotes normalization of clinical and biochemical
      parameters, correction of lipid metabolism and parameters plasma hemostasis.
      Vegetarian antiatherogenis the diet is perspective means in treatment of the
      patients ischemic heart disease of elderly age.

PMID- 12227011
TI  - [Nutrition mixes in the complex rehabilitation of young men with constitutional
      deficit of body weight].
AB  - It was investigated peculiarities of the constitutional malnutrition in 94 young
      men. The influence of oral supplementation by enteral nutrition on recovering 54
      young men with constitutional malnutrition was examined. The results of
      investigation indicated a high efficacy of using oral supplementation in the
      complex treatment of malnourished young men. It results in improvement of
      patient's rehabilitation and reduce the time of hospitalization.

PMID- 12227012
TI  - [Use of a new sugar substitute, erithritol, in the diet therapy of type 2
      diabetes patients].
AB  - It was investigated the influence of a diet supplemented with erithritol on
      dynamic of basal and postprandial glycemia, lipid levels, blood pressure, body
      weight in 30 patients with type 2 diabetes. The results indicated that
      supplementation of erithritol (30 g/day) in traditional hypocaloric diet did not
      decrease the efficacy of dietary therapy in patients with type 2 diabetes. After
      ingestion 30 g erithritol dissolved in 300 ml of water, blood glucose did not
      show a marked increase in compared with 30 g isomalt (control).

PMID- 12227013
TI  - [Medical-biological evaluation of genetically-modified sugar beet line 77
      (chemical composition and toxicologico-biochemical studies)].
AB  - The rats were fed with the Genetically Modified Sugar Beet line 77 (Monsanto Ko,
      USA) 10 g/rat/day for 1 month. Their blood, urea and liver were investigated to
      measure total protein and glucose levels, aminotransferase and alkaline
      phosphatase activities, pH, creatinine level as well as hepatic enzyme activity
      of the I and II phases of xenobiotic metabolism and whole and non-sedimentated
      lysosomal enzyme activities and activity of antioxidant system.

PMID- 12227014
TI  - [Medico-genetic evaluation of sugar sand, obtained from genetically-modified
      sugar beet line 77 (toxicologico-biochemical studies)].
AB  - The rats were fed with the Suger from the Genetically Modified Suger Beet line 77
      (Monsanto Ko, USA) 3 g/rat/day for 3 months. Their blood, urea and liver were
      investigated to measure total protein and glucose levels, aminotransferase and
      alkaline phosphatase activities, pH, creatinine level as well as hepatic enzyme
      activity of the I and II phases of henobiotic metabolism and whole and non
      sedimentated lysosomal enzyme activities and activity of antioxidant system.

PMID- 12227015
TI  - [Vitamin sufficiency to preschool and young school age children from a group at
      risk for emergence of bone mineralization disorders].
AB  - Vitamin status of 36 children 5-8 years old (Moscow) from the decreased bone
      mineral density risk group has been evaluated. Only 6-14 per cent of children had
      deep vitamin deficit. Vitamin B1 and B2 insufficiency has been observed 1.6 fold
      rarely among children additionally receiving vitamin supplement. The relation
      between urinary calcium and vitamins B1, B2 and B6 excretion has been shown. No
      difference was found in calcium excretion rate irrespective of additional vitamin
      intake. Although no correlation between urinary calcium/creatinine excretion and
      urinary vitamins C, B1, B2 and B6 excretion has been found children with
      increased calcium/creatinine index are insufficiently supplied with four vitamins
      more often. The data obtained could not be regarded as negation of the vitamin
      sufficiency importance for calcium metabolism and osteogenesis disturbance
      prevention.

PMID- 12227017
TI  - [Effect of erithriol on intestinal microflora and morphology of rat internal
      organs].
AB  - In experiences on rats is shown, that 22 daily upkeeping of animals on a diet
      including eritrit in a dose 1 g/weight of a body, do not cause any changes from
      the party intestinal microflora and morphological structure of internal bodies.
      However, the specified doze eritrit causes statistically authentic increase of
      levels conditionally-pathogenic anaerobius of the representatives microflora,
      first of all staphylococcus and citratessimilation enterobacteria.

PMID- 12227016
TI  - [Limiting the allowable concentration of zearalenone in processed grain
      products].
AB  - The distribution zearalenon (ZL) in products of processing of contaminated wheat,
      barley and maize grains was is investigated. Results of the data analysis on the
      investigation of an actual nutrition of the population in Russia is presented;
      the share of products of processing of contaminated wheat, barley and maize
      grains as part of the total ration was determined Varied values of Maximum
      Acceptable Concentration (MAC) of ZL based on the obtained results are offered: 1
      mg/kg--for wheat, barley and maize grains; 0.2 mg/kg--for main products of grain
      processing, viz flour and groats. The application of these MAC-values for ZL
      ensures the conformity between the ones for raw materials and for products of
      processing of raw materials, as well as the limitation of the maximum possible ZL
      -intake within the bounds of Acceptable Daily Intake (ADI) for a man.

PMID- 12227018
TI  - [Features of the effect of saturated and unsaturated fatty acids on lipid
      metabolism, lipoproteins, and development of ischemic heart disease].
AB  - The effect of saturated, mono- and polyunsaturated fatty acid on lipid,
      lipoprotein metabolism and ischaemic heart disease is reviewed. Optimal effect on
      lipid and lipoprotein metabolism and prevention of ischemic heart disease exert
      only physiologically correlated amount of saturated and unsaturated fatty acid.
      Especially negative metabolic action is noted by use of heated oils contained
      polyunsaturated fatty acids.

PMID- 12227019
TI  - [Zinc in human nutrition: physiological needs and bioavailability].
AB  - The zinc is one of basic essential trace-elements in human nutrition. The problem
      of the determination of zinc requirements in man is discussed in view of an
      appearance of adaptation to various levels of this trace element in a diet and
      degree of its bioavailability in basic kinds of foodstuff. The problem of
      evaluation of zinc bioavailability is highlighted from the positions of zinc
      absorption mechanisms based on the research data which have been obtained in
      model systems and in vivo in human and laboratory animals.

PMID- 12227020
TI  - [Effect of an anti-atherogenic diet, including soy protein products with various
      levels of phytoestrogens, on indicators of humoral immunity in patients with
      hypertension and ischemic heart disease].
AB  - The dynamic of level of natural antibodies to factors of blood coagulation system
      (thrombin, antithrombin III, alpha 2-macroglobulin), to angiothensinogen and to
      noradrenaline in 95 patients with ischemic heart disease and hypertension was
      studied in antiatherosclerotic diet and diet with soy-protein (soy protein
      isolate and soybean flour). Universal normalizing effect of the diet with soy
      protein consist in increase of levels of natural antibodies to thrombin,
      antithrombin III, alpha 2-macroglobulin, angiothensinogen and to noradrenaline.

PMID- 12227021
TI  - [Epidemiology and laser correction of chronic diseases observed in snoring and
      obstructive sleep apnea].
AB  - Investigations of snoring have been initiated because snoring is associated with
      obstructive sleep apnea syndrome (OSAS) and some chronic diseases eventuating in
      invalidity. Questionnaire survey provided evidence on snoring and OSAS incidence
      among different age groups of male and female population of St-Petersburg.
      Associated chronic diseases were also evaluated. Snoring and OSAS were corrected
      by laser uvulopalatoplasty. The correction was conducted in the contact regimen
      by Nd-YAG laser. As a result of the treatment, snoring and apnea in mild OSAS
      ceased in all the patients and decreased by at least 60% in severe OSAS. This
      effect was confirmed by polysomnographic findings.

PMID- 12227022
TI  - [Clinical features of neurohumoral regulation of the vascular tonus in patients
      with recurrent nasal bleedings].
AB  - Norepinephrine (NE), dopamine, histamine and serotonin levels in the blood were
      measured fluorometrically in 54 patients with nasal bleedings (NB) aged 15 to 23
      years. Of them, 18 patients suffered from habitual NB, 36 had NB because of
      hypertension. Biogenic amines were studied before and after graded exercise (GE).
      Low basal levels of serotonin, NE and dopamine were found in all the examinees.
      Patients with habitual NB had also high basal level of histamine. Such
      correlation of biogenic amines points to abnormal relations between
      vasoconstrictive and vasodilating mechanisms of neurohumoral vascular regulation
      disturbing microcirculation in nasal mucosa, suppresses tonicity of the
      capacitive vessels, leads to their overfilling, progression of circulatory
      hypoxia and metabolic acidosis, makes bleedings recurrent. Similarity of
      neurohumoral adaptation reactions to GE in patients with habitual and
      hypertensive NB suggests the presence of the same mechanisms of NB onset and
      their recurrences in various primary causes.

PMID- 12227023
TI  - [Characteristics of psychoemotional sphere in children with chronic laryngeal
      obstruction].
AB  - 45 children from 10 to 14 years of age with chronic laryngeal obstruction were
      examined psychologically. 29 of them had recurrent respiratory papillomatosis, 16
      ones had cicatrical laryngostenosis. The majority of the examinees (65%) showed
      symptoms of posttraumatic stress syndrome (PTSS). The children develop PTSS one
      two years after onset of laryngeal obstruction. Later, the children underwent
      persistent specific maladaptation personality disorders. Thus, children with
      recurrent laryngeal papillomatosis, especially with cicatrical laryngostenosis,
      should undergo psychological correction.

PMID- 12227024
TI  - [Equilibrium function in patients with acute sensorineural hearing loss].
AB  - Equilibrium function was investigated with computer-assisted stabilography (CS)
      in patients with acute neurosensory hypoacusis. This new diagnostic tool was
      employed in combination with extended vestibulometric and audiologic
      examinations. Correlations were found between stabilographic and vestibulometric
      findings. CS is recommended as a method of screening diagnosis in examination of
      patients with imbalanced equilibrium.

PMID- 12227025
TI  - [Spiral computed contrast tomography in diagnosis of juvenile angiofibroma of the
      base of the skull].
AB  - The authors present their experience in surgical and combined treatment of
      juvenile angiofibroma of the base of the skull (JABS). A total of 180 children
      were treated, 93.8% of them had advanced tumor and were operated through external
      approach by Moore. Computed and MR tomographies were made preoperatively and
      postoperatively in all the patients. Benefits and drawbacks of the above
      tomographies are analysed. A technique of spiral computed contrast tomography in
      JABS is described. This tomography has the following advantages: volume
      visualization of the studied area without artefacts induced by movements; sharper
      visualization of the vessels; possibility of retrospective reconstruction of the
      sections with varying interval after the end of the procedure; improved quality
      of multi-plane reconstructions; reduced radiation dose and time of exposure.

PMID- 12227026
TI  - [Anti-leukotriene therapy of patients with allergic rhinosinusitis and bronchial
      asthma].
AB  - The authors review current knowledge on pathogenesis of allergic rhinosinusitis
      and bronchial asthma and their relations, show the role of leukotriens in
      development of respiratory allergy, characterize antileukotrienic medicines.
      Eleven patients with allergic rhinosinusitis and bronchial asthma received
      monotherapy with zafirlucast (acolapt) which is a blocker of leukotrienic
      receptors. Eight patients benefited from the treatment. The positive effect
      consisted in improvement of nasal respiration, reduction of rhinorrhea, edema of
      nasal mucosa, size of polyps.

PMID- 12227027
TI  - [Clinical aspects of a virtual operating room for the prediction of operative
      interventions in some disease of the middle ear].
AB  - Clinical aspects of creating a software system for simulation and prediction of
      operative interventions and hearing function changes are considered. The system
      will make simulation and prediction transparent and convenient for the user. The
      technical challenge is to create mediation languages which enforce rigorous
      mathematical computation while supporting intuitive behaviour. The prevalent
      textual interface of command lines and pull-down menus is replaced by physical
      behaviour within an environment. The system is based on new possibilities of
      computer-integrated environments for problem solving such as virtual environments
      and it will be presented in a form of a virtual operating room. The following
      aspects are taken into consideration: a model of the middle ear, database for
      existing methods of operative interventions, x-ray and computed tomography
      imaging of the temporal bone, determination and localization of otosclerosis
      foci, modeling and determination of acoustic parameters for transplantation
      materials, simulation and prognosis of potential complications.

PMID- 12227028
TI  - [Correction of autonomic sensory disorders in middle ear diseases].

PMID- 12227029
TI  - [Remote postoperative results of various surgical methodologies and the postop
      status of maxillary sinuses].
AB  - The paper presents a comparative analysis of surgical outcomes in chronic
      maxillary ethmoiditis for radical and endonasal endoscopic operations in 85
      patients. Objective control was performed with morphological, endoscopic and
      functional methods.

PMID- 12227030
TI  - [Effectiveness of the treatment of frontal sinus inflammation and its
      prevention].
AB  - The analysis of intraoperative data obtained at correction of ethmoid bone
      structure in 130 patients with frontal sinusitis including the removed tissue
      histology shows that the severity of ostiomeatal complex deformation correlates
      with actual advance of the destructive alterations in the ethmoid labyrinth by
      the frontal sinus. Removal of necrobiotic tissues adjacent to the frontal sinus
      is pathogenetically valid and the most effective treatment of frontal sinusitis
      which has reduced the number of recurrences to 3.5%.

PMID- 12227031
TI  - [Immunotherapy of patients with acute and chronic sinusitis with preparation IRS
      19].

PMID- 12227032
TI  - [Medicines against cold. Notes by the medical director of a Russian department of
      one of the Western pharmaceutical companies, working in Russia in the
      prescription-free medication market].

PMID- 12227033
TI  - [Hearing and speech therapeutical services to the population of the Moscow region
      (contribution of Prof. M. A. Shuster in its organization].

PMID- 12227034
TI  - [Otogenic tetanus in children].

PMID- 12227035
TI  - [A case of an accessory tongue].

PMID- 12227036
TI  - [Invasive vascular tumor of the oropharynx].

PMID- 12227037
TI  - [Local treatment of patients with chronic purulent otitis media].

PMID- 12227038
TI  - [High-energy laser radiation in otorhinolaryngology: past and future].

PMID- 12227039
TI  - [V. I. Voiachek and Russian otorhinolaryngology (125 years since his birth)].

PMID- 12227040
TI  - [Characteristics of autonomic dystonia in children with vasomotor rhinitis].
AB  - Data obtained at analysis of tables of screening diagnosis, cardiointervalograms,
      tilt tests used in examination of 57 children with neurovegetative vasomotor
      rhinitis point to disorders in the autonomic nervous system (by initial
      vegetative tone), vegetative reactivity. Parasympathetic prevalence in the
      initial vegetative tone and cardiointervalograms stems from sympathetic
      hypoactivity in the majority of the patients. The above vegetative shifts dictate
      the necessity of vegetotropic medication inclusion into combined therapy of
      vasomotor rhinitis.

PMID- 12227041
TI  - [Awareness of patients of tuberculosis dispensaries and their attitude to
      therapeutical process].
AB  - The awareness of tuberculosis was studied among patients of tuberculosis
      dispensaries. A survey indicated that as high as 2.3% of the patients with
      tuberculosis gave right answers to all the questions of a questionnaire. 61.8% of
      the respondents answered the bulk of the questions. The latter can be arbitrarily
      considered to be aware of their disease. The persons who are unaware of
      tuberculosis are more commonly males with a below-secondary educational level,
      patients above 50 years, the unemployed, and low class. More than half of such
      patients are not sure that they will be able to recover, which makes them refuse
      treating. Better awareness can enhance the results of treatment and the outcomes
      of the disease.

PMID- 12227042
TI  - [Results of introduction of extended WHO program for detection and treatment of
      patients with tuberculosis of the respiratory organs].
AB  - Data on 283 new cases of tuberculosis receiving an intensive course of
      controlled, short-term, and WHO-standardized chemotherapy were studied.
      Mycobacteria tuberculosis were detected in 71.4% of patients by bacterioscopy,
      predominantly in tuberculosis dispensaries. In the general health care
      facilities, fluorography remains to be the method of choice in detecting
      tuberculosis. The factors increasing a risk for tuberculosis were established in
      most (71.7%) patients, social disorientation being most common. After the
      intensive stage of treatment, sputum smear conversion was achieved in 87.2% of
      the patients. Before the end of treatment, the majority of patients (72%)
      subsequently quitted a follow-up for these and those reasons. After completion of
      maintenance therapy, recovery was achieved in 81% without taking into account the
      patients with sputum smear conversion but with remaining decay cavity. The poor
      course and recurrences were encountered mainly in socially disoriented persons or
      in the presence of other risk factors, in compliance, and preserved caverns after
      termination of chemotherapy. A number of recommendations are made.

PMID- 12227043
TI  - [Work of the tuberculosis control service in the Ryazan Region under changing
      socioeconomic and epidemic conditions].

PMID- 12227045
TI  - [Effectiveness of the use of ultrasound irradiation of the spleen in patients
      with acutely progressive pulmonary tuberculosis].
AB  - Sixty-three patients with acute progressive tuberculosis (APPT) underwent splenic
      ultrasound radiation (SUSR) (Group 1) for evaluation of the efficiency of the
      procedure. A hundred and twenty five patients with APPT were treated without SUSR
      (Group 2, controls). An experimental study was also conducted on 290 mice. SUSR
      was also used in the late first month of antituberculous chemotherapy. A
      procedure for SUSR is described in the paper. There were most favourable clinical
      and X-ray changes in Group 1 than in Group 2 just after SUSR and at the end of
      the treatment course. After the procedure (first control) all biochemical
      inflammation indices (medium molecular-weight molecules, adenosine deaminase,
      fibrinogen, sialic acids) were significantly decreased in Group 1. Immunological
      indices were insignificantly changed between groups and primary investigations. A
      study after two months of SUSR showed no differences in biochemical indices in
      the groups and in this period as compared to the control one. At the same time,
      the levels of CD cells, especially CD8+, were found to be lower in Group 2. In
      Group 1, the count of CD cells and their functional activity by the blast
      transforming reaction on PHA were stable and significantly higher than in Group
      2. The experimental study demonstrated that the levels of medium molecular-weight
      molecules and the index of lung damage reduced after SUSR. The decrease in the
      count of MBT colonies and a positive response in the murine paw test, which is
      indicative of T-cell immunodeficiency, were detected one month following the
      procedure (distant control). So SUSR should be proposed as a new effective
      pathogenetic treatment for APPT.

PMID- 12227044
TI  - [Clinical value of microchip technology in determination of drug resistance of
      Mycobacterium tuberculosis].
AB  - The patients with multiresistant tuberculosis were divided into 2 groups: the
      sensitivity of Mycobacteria tuberculosis to antituberculous drugs was evaluated
      in Group 1 by the methods of absolute concentrations and in Group 2 by biological
      microchips determining mutations in the rpo3 gene responsible for rifampicin
      resistance. The results of the drug sensitivity test were obtained after 3 months
      of treatment in Group 1 and several days prior treatment in Group 2. By taking
      into account the test results, reserve drugs was used in Group 2 patients.
      Subsequently, the results of the drug sensitivity tests carried out by the
      bacteriological method in Group 2 patients showed that isoniazid resistance was
      simultaneously noted if there were mutations in the rpo-B gene. Timely treatment
      with reserve drugs exhibited higher efficiency of treatment with its shorter
      duration in Group 2 than in Group 1.

PMID- 12227046
TI  - [Tuberculosis in patients with HIV infection: clinico-morphological and
      epidemiological aspects].
AB  - A contingent of patients with pulmonary tuberculosis concurrent with HIV
      infection in 1997 and 1999 is analyzed. The first analysis covers all cases of
      this combined pathology occurring in Russia throughout the notification of HIV
      infection in the country. The specific features of the course of tuberculosis
      have been defined in relation to the stage of HIV infection. The second analysis
      involved the data on such patients in 59 subjects of the Russian Federation in
      1999. It has shown that there are changes in the composition of the contingent
      that has combined pathology, which is associated with the HIV transmission route
      that is new for Russia. This in turn resulted in that patients with HIV infection
      were much more frequently detected at the tuberculosis facilities. The altered
      HIV-infection epidemic situation enhances the topicality of this problem for
      phthiologists.

PMID- 12227047
TI  - [Migration of CD4+ and CD8+ lymphocytes into the internal lining of tuberculous
      pleural empyema and tuberculous caverns during their local sanitation].
AB  - Cytological, immunological, and microbiological findings after sanitation of
      pulmonary caverns and pleural empyemas were analyzed in 13 patients: 7 with
      empyemas of residual pleural cavities after surgery for pulmonary tuberculosis
      and 6 with fibrocavernous pulmonary tuberculosis. It has been found that target
      sanitation of the intrapulmonary and intrapleural cavities enhances lymphocytic
      penetration into the internal part of the cavitary wall, infiltrating lymphocytes
      represent mainly CD4+ cells whose count progressively increases with successful
      sanitation, as appeared as a significant rise in both the so-called
      immunoregulatory index (CD4+/CD8+ ratios of 3.4 to 6.1). A study of the
      populational composition of lymphocytes promotes an objective evaluation of the
      magnitude of a specific tuberculous inflammatory process in the wall of the
      cavity of empyemas and caverns.

PMID- 12227048
TI  - [Removing of the remaining parts of the lung by the pulmonectomy type in
      tuberculosis reactivation after partial resect ions].
AB  - The outcomes of reoperation--removal of the remaining parts of the lung by the
      pulmonectomy type--for tuberculosis reactivation after partial lung resections
      were studied in 51 patients. A 3-5-month comprehensive preoperative preparation
      promoted stabilization of a tuberculous process in the lung in 31 (60.8%)
      patients, partial stabilization in 13 (25.5%). A progressive clinical course was
      observed in 7 (13.7%) patients receiving antibiotic therapy. The good immediate
      efficiency of pulmonectomy (76.9%) and postoperative clinical recovery (84.1%)
      show that this treatment is justifiable and expedient for critically ill
      patients.

PMID- 12227049
TI  - [Low-intensity laser irradiation in the treatment of patients with tuberculosis
      of the urinary system].

PMID- 12227050
TI  - [New stage of tuberculosis control in Russia].

PMID- 12227051
TI  - [Clinical picture of genital tuberculosis in different forms of its pathogen].
AB  - Improvement of bacteriological diagnosis is of great value for the clinical
      picture of genital tuberculosis. The purpose of the study is to reveal the
      clinical features of genital tuberculosis in L-forms of Mycobacterium
      tuberculosis (MBT) versus traditional bacteriological methods and polymerase
      chain reaction (PCR) test with MBT DNA. A hundred and fourteen patients with
      verified active genital tuberculosis were examined. They were divided into 3
      groups: 1) 36 patients with L-forms of MBT in the endometrial scrapes; 2) 32 with
      bacteriologically verified GT; 3) 46 with positive PCR test. A control group
      (Group 4) comprised 120 patients with NGD. Among the patients with L-forms there
      were prevalent females aged 21-40 years (83.4%). These patients had a history of
      spontaneous abortions more frequently than patients from other groups, in a third
      was found to have MBT with their L-variants. Signs of intoxication were observed
      in 47.2%. Oviductal obliteration and specific changes typical of tuberculosis
      were revealed on a hysterogram in 63.9%, other forms of prior and current
      extragenital tuberculosis were detected in a half of cases, traces of prior
      pulmonary tuberculosis were observed in 15%, 63.9% of the patients with L-forms
      and in 87% of those with positive PCR test were found to have pathological
      changes in the endometrium, which is indirectly indicative of its lesion. Thus,
      detection of L-forms of MBT in the endometrial scrapes leads to the conclusion
      that this is an active sluggish hematogenic tuberculous process, which is
      evidenced by a complex clinical and laboratory study.

PMID- 12227052
TI  - [A case of isolated hepatic tuberculosis].

PMID- 12227053
TI  - [Goodpasture syndrome].

PMID- 12227055
TI  - [Tuberculosis in migrants and its impact on the epidemic situation in a large
      megalopolis].

PMID- 12227058
TI  - [Diagnosis of postvaccinal complications after administration of BCG vaccine.
      (Methodical recommendations No. 99/219].

PMID- 12227059
TI  - [Digital fluorographs for early detection and diagnosis of pulmonary
      tuberculosis].
AB  - Under the conditions of out health care system it is best to install first small
      dose digital fluorographs at urban polyclinics and use as movable plants. The
      basis of a diagnostic study of pulmonary tuberculosis is to monitor X-ray changes
      in the process by a series of X-ray images and tomographic scans. At the same
      time paper imprints obtained by printers (including laser ones) lose as much as
      30% of image details so computer images rather than hard paper copies should be
      used for comparison in practice of the X-ray units of dispensaries. Computers are
      required for dispensaries: for each X-ray specialist, the head of a unit, deputy
      head physician in therapeutics so that the use of a digital fluorographic plant
      should be as much as effective.

PMID- 12227060
TI  - [ERBB2/HER2: from molecular to clinical oncology].

PMID- 12227061
TI  - [Results, failures and perspectives in therapy of multiple myeloma].

PMID- 12227062
TI  - [Apoptosis: role in normal ontogenesis and in pathologic conditions].

PMID- 12227063
TI  - [Regulation and manifestations of apoptosis in normal tissues and in neoplasms].

PMID- 12227064
TI  - [Biological response modifiers in the treatment disseminated melanoma].

PMID- 12227065
TI  - [Cytogenetic and molecular genetic investigation of melanoma].

PMID- 12227066
TI  - [The role of immunotherapy in the treatment of patients with hematologic
      neoplasms].

PMID- 12227067
TI  - [Role of radionuclide imaging of bone marrow and spleen in choice of therapy and
      topometric preparation for radiotherapy of patients with Hodgkin disease].
AB  - Use of radionuclide methods of bone marrow (BM) and spleen visualization was
      assessed in 176 patients with primary Hodgkin's disease and 116 relapsing cases.
      The study was intended to help design treatment modality and carry out topometric
      measurements for exposure to radiation. Stage of tumor was revised in 19 primary
      patients as a result of BM scintigraphy, and this factor was responsible for
      major changes in the treatment modality in 11 patients (6.2%). This factor played
      a similar role in designing irradiation field boundaries in another 18 primary
      patients (10.2%). Similarly, the choice of treatment modality was revised in 33
      relapsing patients (27.5%). The standard roentgenometric data on the anatomical
      reference points of the spleen and those of radionuclide-assisted visualization
      were compared in 37 patients. In 17 (45.9%), part of the spleen was shown by
      scintigraphy to be outside the irradiation boundaries delineated by the
      roentgenometric procedure. Roentgenometry located the spleen well inside the
      irradiation fields in 8 patients (21.6%). However, due to scintigraphy, their
      boundaries were altered to cut down the exposure of the left kidney (5) or the
      left lung (3). Complete agreement between roentgenometric and scintigraphic
      measurements were reported in 12 patients (32.4%) only.

PMID- 12227068
TI  - [Characteristics and immunologic changes in patients with malignant brain
      tumors].
AB  - The investigation was concerned with assaying immunity and evaluating the role
      played by monocytes and tumor cells in the formation of T-cell dysfunction in
      malignant glioma (MG). The study group included 28 patients with anaplastic
      astrocytomas (n = 18) and glioblastomas (n = 10). MG patients showed significant
      changes in the numbers of CD16+ NK-cells and HLA-DR monocytes as well as lowered
      levels of HLA-DR expression on monocytes and proliferative response of T
      lymphocytes as compared with both standard and alternative pathways of
      activation. Monocytes and macrophages suppressed T-cell activity due to
      production of prostaglandins E2 in such patients. Enhanced immunosuppression was
      also reported in 24-hour supernatants of tumor cells. Immune disorders were shown
      to involve apoptosis-independent mechanisms. Hence, despite the immune privilege
      of the brain, immunocompetent cells crossed blood-brain barrier and counteracted
      with tumor cells. As a consequence, monocyte function and cellular cooperation
      dropped while production of immunosuppressive factors rose, and T-cell
      dysfunction was brought about through apoptosis-independent mechanisms.

PMID- 12227069
TI  - [Effect of new chemotherapeutic methods on the biologic tissue environment and on
      the immune status of patients with breast cancer].
AB  - Standard (SCT), autoplasmochemotherapy using cytostatics preincubation with
      autoplasma (APCT) and autoblood (autohemochemotherapy--AHCT) were compared to
      evaluate their effects on locally advanced breast tumors. SCT showed marked
      immunosuppressor effect while APCT and, particularly, AHCT--a sparing one. The
      use of the latter modalities involved significantly higher levels of active T-,
      NK- and cytotoxic CD+ 8 cells. A comparison of the latter methods also showed
      ABCT to yield a better subset balance between T- and B-cells and a higher level
      of their mitogen response.

PMID- 12227070
TI  - [Non-specific changes in the complement system in neoplastic processes].
AB  - The study using immunochemical and biological methods was concerned with assaying
      complement components C1q, C3, C4, and C5, C3 derivatives--C3a and, C3(H2O),
      C1ing control protein, hemolytic activity (CH50), total proteolytic activity and
      regulatory immune complexes in sera from patients with cancer of the stomach,
      breast and ovary, subjects at risk of cancer and healthy donors. Neoplasia was
      associated with lowered levels of intact C3 and C1ing matched by high
      concentrations of C3a, C1q and C4. Hemolytic activity (CH50) was increased
      against the background of relatively higher total proteolytic activity both in
      healthy subjects and cancer patients. Significant decrease in C1ing concentration
      may be used as an additional biochemical prognosticator in breast cancer.

PMID- 12227071
TI  - [Apoptosis-inducing and anti-tumor effect of cyclophosphamide, cisplatin and
      adriamycin used separately or combined in murine lymphosarcoma LS].
AB  - The investigation deals with antitumor effect of cyclophosphamide, platin and
      adriamycin on transplantable mouse lymphosarcoma LS. It was found that the effect
      of the most potent drug cyclophosphamide is mediated mostly by apoptosis, while
      those of platin and adriamycin--by apoptosis and necrosis of tumor cells. When a
      combination of two or three drugs was used the necrotic effect increased
      proportionally, while the apoptotic one decreased. However, the overall antitumor
      effect did not exceed that of the one drug which induced apoptosis most
      effectively.

PMID- 12227072
TI  - [Role of the antioxidant system of the brain in the antineoplastic mechanism of
      ultra-low frequency magnetic fields].
AB  - The study deals with the possible effects of ultra low frequency magnetic fields
      (ULF MF) on carcinogenesis in the brain and oxidative metabolism disorders
      associated with it. Animals were exposed to modulated ULF MF at pathogenetically
      sensitive stages of the "biochemical restructuring" of the body. This allowed to
      adjust carcinogenic development by extending latent period of tumor and life span
      of tumor-bearing animals. To counter carcinogenesis, ULF MF were used to help
      build stable antioxidative links, both enzymatic and non-enzymatic, and stimulate
      their performance at early stages of tumorigenesis.

PMID- 12227074
TI  - [Diagnostic errors in primary multiple synchronous malignant neoplasms].

PMID- 12227073
TI  - [Antitumor cross-resistance of trichinosis].
AB  - Our experiments were concerned with formation of antitumor cross-resistance by
      Trichinella spiralis infection in rats. Prophylactic infection was followed by an
      insignificant decrease in the number of 3,4-benzpyrene-induced malignant fibrous
      histiocytoma. It also inhibited mammary gland cancer induced by 7,12
      dimethylbenzo(a)anthracene. No significant influence on the formation of
      fibroadenomas as a side effect was reported.

PMID- 12227075
TI  - [Cytologic differential diagnosis of various peripheral lung cancers].
AB  - The data on 25 cases of histologically verified bronchioloalveolar carcinoma and
      papillary adenocarcinoma are discussed. Reliable differential diagnostic
      cytological features of both diseases were established using a statistical,
      program and fine-needle biopsy findings. Statistical analysis data pointed to the
      sets of cytological features: "serial pattern--clear cell boundaries" and "serial
      pattern--presence of macrovacuoles" as a major factor of accuracy of bronchiolo
      alveolar carcinoma and papillary adenocarcinoma diagnosis. These cytological
      features may be used for reliable diagnosis of the diseases.

PMID- 12227076
TI  - [Doppler investigation of blood flow in uterine vessels of patients with
      endometrial cancer].
AB  - 125 suspects for endometrial pathology were examined to evaluate clinical
      significance of color Doppler sonography for comprehensive diagnosis of
      endometrial carcinoma. This pathology was identified in 114; atypical hyperplasia
      -11. The data on combined application of traditional ultrasound and color Doppler
      sonography were compared with those on clinical and postoperative histological
      examinations. The combined method proved the most informative both in primary
      diagnosis of endometrial carcinoma and assessment of invasion into the
      myometrium. The specific features of blood supply to carcinoma are discussed.

PMID- 12227078
TI  - [Economic aspects of specialized preventive screening for breast cancer].
AB  - Economic problems involved in specialized mammographic screenings carried out
      among the workers of the City of Perm and the region were studied. The
      investigation was funded on a contract basis and no budget money was used. During
      9 years, 61,276 women aged 17-72 (up to 20 years old--2.3%; 21-31--16.9%; 31-40-
      34.5%; 41-50--29.4%; 51-60--14.2%, and older than 60 years--2.7%) were examined.
      The costs of examination of all the patients by mammologist ran up to
      Rbl.464,251; mammography (MG)--Rbl.13,374; ultrasound (US)--Rbl.26,880, and
      aspiration biopsy--Rbl.14,852. The total cost was Rbl.716,490, or Rbl.11.7 ($0.4)
      per screenee. Cancer was diagnosed in 62 (stage I-II--90.3%). Each detection cost
      Rbl.11,556 ($398), or less by 33% (Rbl.7,727; $266) if the costs of MG and US,
      which failed to make any significant contribution, are subtracted. Also, 1,638
      precancerous benign tumors were identified (each case--Rbl.437; $15). It is
      suggested that the actual costs of tumor detection make a case for further
      application of mass screenings.

PMID- 12227077
TI  - [Role of interventional radiography in the treatment of the hepato-pancreato
      duodenal area, complicated by obstructive jaundice].
AB  - We assessed the role of interventional radiological procedures used in the
      treatment of patients with hepatopancreatobiliary cancer complicated by
      obstructive jaundice. Between 1990 and 2000, 71 patients underwent percutaneous
      transhepatic biliary drainage (PTBD): external drainage--18 (group A); external
      internal drainage or stenting (group B), and external-internal drainage or
      stenting plus chemoinfusion or chemoembolization of the hepatic artery--15 (group
      C). Mean survival (M(SD) calculated for patients who died was 2.1(0.5 mo for
      group A; (pb,c(0.01), 7.9(6.7 mo (group B), and 16.6(14.8 mo for group C (NS with
      B). The actual one-year survival was 10, 25, and 45%, respectively. External
      internal PTBD and stenting are safe effective palliative procedures for patients
      with malignant obstructive jaundice. Survival in patients with
      hepatopancreatobiliary cancer doubled after chemoinfusion or chemoembolization,
      without grave complications or lethality.

PMID- 12227079
TI  - [Diagnostic potential of fiberoptic cervico-hysteroscopy with morphologic
      examination of biopsied tissues in endometrial and cervical malignancies].
AB  - Fibrocervicohysteroscopy (FCHS) is a highly informative method of visual
      diagnosis of various endometrial and cervical pathologies (benign and malignant
      polyps, hyperplasia including atypical glandular one) and endometrial carcinoma
      (including involvement of the cervical canal). The accuracy of FCHS will be
      further increased if it is used in conjunction with morphological (cytologic and
      histologic) examination of hysterobioptates.

PMID- 12227080
TI  - [Frequency of infertility in endometrial cancer].
AB  - A retrospective study included 1,559 patients with endometrial carcinoma who had
      received surgical and combined treatment (1968-1995). It was found that
      infertility was at the background of practically all cases under the age of 30
      (92.3%). Moreover, high rates of infertility were discovered in the histories of
      patients with light-cell (mesonephroid) carcinoma which developed in menopause.

PMID- 12227081
TI  - [Alexander Ivanovich Rakov (birthday centenary)].

PMID- 12227082
TI  - Continuum of care: stabilizing the acutely agitated patient.
AB  - The safety and efficacy of i.m. ziprasidone and olanzapine for treating acute
      agitation in patients with schizophrenia are described, along with factors to
      consider when evaluating the cost-effectiveness of these agents. Agitation is
      defined as excessive motor and verbal activity. Acute agitation has traditionally
      been treated with the combination of haloperidol 5 mg and lorazepam 2 mg i.m.
      Controlled trials have shown, however, that combination therapy of haloperidol or
      droperidol plus lorazepam i.m. is better than single-drug treatment at one hour
      but not earlier. Phase II and III clinical trials showed that both i.m.
      ziprasidone mesylate 10 mg and 20 mg and olanzapine 2.5 mg-10 mg controlled
      agitation faster in patients with schizophrenia than p.o. ziprasidone 2 mg and
      placebo. In addition, i.m. olanzapine 10 mg controlled agitation faster in
      patients with schizophrenia faster than haloperidol in 15 minutes. Olanzapine
      i.m. was also superior to placebo in patients with dementia and in patients with
      bipolar disorder with and without psychotic symptoms, suggesting that agitation
      may be a syndrome that is similar across a multitude of disease states. Dystonic
      reactions occurred in 2.6% of patients taking ziprasidone, compared with 9.2% of
      patients taking haloperidol. No patients receiving olanzapine experienced a
      dystonic reaction. Ziprasidone has been associated with prolonged QTc Intervals.
      Pharmaco-economic evaluations should include costs associated with repeat i.m.
      injections for agitated patients, increased time in the emergency room, case of
      switching from i.m. to oral therapy, adverse effects, and relapse, as well as
      medication costs. I.m. olanzapine and ziprasidone show promise for treating acute
      agitation in patients with schizophrenia, especially because of their safer
      adverse effect profile and faster onset of effectiveness compared with
      haloperidol.

PMID- 12227083
TI  - Clinical issues associated with maintenance treatment of patients with
      schizophrenia.
AB  - Issues to consider when evaluating maintenance drug therapy for patients with
      schizophrenia are discussed; these include potential adverse effects of
      antipsychotic therapy, such as weight gain, diabetes mellitus, extrapyramidal
      symptoms, sexual dysfunction, cognitive dysfunction, and cardiac effects, as well
      as quality of life. Patients with schizophrenia are more likely to be overweight
      than the general population. Olanzapine and clozapine have been associated with
      the greatest weight gain of the newer antipsychotics. While patients with
      schizophrenia are at increased risk of developing diabetes mellitus independent
      of antipsychotic therapy, diabetes may be more prevalent in patients taking the
      newer agents. Acute extrapyramidal symptoms occur in 75-90% of patients receiving
      first-generation antipsychotics like thioridazine and haloperidol. The
      probability of tardive dyskinesia (TD) occurring with second- and third
      generation agents is less than 1% per year, compared with about 5% per year for
      the traditional antipsychotics. When patients are switched from a traditional
      antipsychotic to clozapine or olanzapine, TDs usually abate somewhat.
      Thioridazine causes a pronounced prolongation of the QTc interval, which can lead
      to ventricular arrhythmias. The slight increase in QTc interval caused by
      ziprasidone most likely will not be a problem in healthy individuals. Newer
      antipsychotics are associated with improved neurocognitive functioning and most
      cause less prolactin elevation, compared with traditional agents. The newer
      antipsychotic agents are not devoid of adverse effects, but those that do occur
      can be managed. Once issues related to adherence are resolved, rehabilitation of
      patients with schizophrenia will be a high priority.

PMID- 12227084
TI  - Comprehensive understanding of schizophrenia and its treatment.
AB  - An overview of schizophrenia is presented, including diagnostic criteria,
      etiology, neurologic findings, pharmacotherapy options, quality-of-life issues,
      and the financial impact of the disease. Schizophrenia is a chronic disease
      characterized by positive symptoms, negative symptoms, mood symptoms, and
      cognitive deficits. Often comorbid substance abuse is present. Schizophrenia
      accounts for 20% of all hospital bed-days and over 50% of all psychiatric beds in
      the United States. There is a strong genetic component to schizophrenia, and
      other possible contributing factors are explored. The diagnostic workup should
      include a detailed longitudinal history, mental status exam, physical and
      neurologic exams, and laboratory tests. A magnetic resonance imaging scan can
      rule out structural causes of psychosis and should be considered at the time of
      diagnosis. Treatment is based on a biopsychosocial model including
      pharmacotherapy in combination with individual, group, and family therapies.
      Rather than classifying antipsychotics as typical or atypical, a new
      classification scheme has been proposed based on risk of causing extrapyramidal
      symptoms and tardive dyskinesia (TD), effect on prolactin level, and efficacy
      profile: first-generation or traditional agents (e.g., chlorpromazine and
      haloperidol); second-generation agents (e.g., risperidone and ziprasidone); and
      third-generation agents (e.g., clozapine, olanzapine, and quetiapine). The
      binding affinities of antipsychotics in the brain help explain the mechanisms by
      which different antipsychotics alleviate specific symptoms of schizophrenia, as
      well as cause specific adverse effects. Improved cognition, fewer depressive and
      mood symptoms, and decreased risk of TD associated with third-generation
      antipsychotics have improved the quality of life for patients with schizophrenia.

PMID- 12227085
TI  - [Effect of a nibentan derivative LKhT53-91 on the heart electrophysiological
      parameters].
AB  - The compound LKhT5391 (a derivative of nibentan) affects the electrophysiological
      cardiac parameters to a lower extent than does nibentan. Administered in an
      effective antiarrhythmogenic dose (comparable with the effective dose of
      nibentan), LKhT5391 produces a less pronounced and shorter negative chronotropic
      action than does nibentan. The negative dromotropic effect of the compound
      studied is manifested only in the atrioventricular node, while not influencing
      conductivity through the atria and ventricles.

PMID- 12227086
TI  - [Effect of emoxypine on myocardial electrical instability and homeostasis
      parameters in patients with acute disturbance of cerebrovascular circulation].
AB  - The frequency of myocardial ischemia onsets, QT interval dispersion, homeostasis
      characteristics, and lipid peroxidation parameters were studied in a group of 49
      patients with acute disturbance of cerebral circulation (ADCC). The Holter ECG
      monitoring revealed myocardial ischemia episodes in 42% of patients, and
      myocardial instability manifested by the QT interval variance in 82% of patients.
      The control group (30 patients) received standard complex therapy, while the test
      group (19 patients) additionally received emoxypine. The administration of
      emoxypine reduced the incidence of myocardial ischemia and positively influenced
      the QT interval variance and the main parameters of homeostasis.

PMID- 12227087
TI  - [Potential gastroprotective effect of a CysLT1 receptor blocker sodium
      montelukast in aspirin-induced lesions of the rat stomach mucosa].
AB  - Montelukast sodium, a specific leukotriene receptor (CysLT1) blocker administered
      orally in a dose of 40 mg/kg prevented the stomach mucosa in rats from acute
      erosive gastritis model induced by acetylsalicylic acid (150 mg/kg, p.o.) in male
      albino Wistar rats. The potential role of a "5-lipooxygenase shunting" of the
      arachidonic acid metabolism in the gastrointestinal toxicity of non-selective
      cyclooxygenase inhibitors is discussed.

PMID- 12227088
TI  - [Gastroprotective effect of lycopene in acute gastritis induced by
      hydrocortisone].
AB  - Lycopine in a daily dose of 0.2 mg/kg produced a gastroprotector effect on the
      model of hydrocortisone-induced gastritis in rats. A change in the dosage (toward
      significant increase or decrease) significantly reduces the gastroprotector
      effect.

PMID- 12227089
TI  - [Effect of furosemide on the intrarenal hemodynamics and excretory renal function
      depending on salt regime].
AB  - The experiments on rats showed that the dietary mineral composition influences
      renal circulation and saluretic function and modifies the related effects of
      furosemide. In particular, a high NaCl intake reduces the blood perfusion in the
      renal cortex and increased that in the renal medulla, thus increasing sodium
      excretion with urine. The use of hyposol, a table salt substituent, enhances the
      blood flow in the renal medulla and leads to a significant increase in the
      diuresis, natriuresis, and kaliuresis. Furosemide (10 mg/kg) sharply increases
      the medullar circulation and electrolyte excretion on the background of standard
      diet. However, these effects were much less pronounced on the background of
      hypersodium diet or hyposol administration.

PMID- 12227090
TI  - [Comparative evaluation of the antiradical and antioxidant activity of estrogens
      and their nitro derivatives].
AB  - Estradiol, ethynylestradiol, and estradiol acetate possess antiradical activity
      (K7 = (1.8-2.0) x 10(-4) liter/mole sec). Nistranol exhibits antiradical
      properties only upon acid hydrolysis. The results of experiments with egg yolk
      liposomes showed evidence of a pronounced antioxidant activity of estradiol,
      ethynylestradiol, and estradiol nitrate, and the absence of such activity in
      nistranol. In the experiments on rat heart homogenates, nitroestrogens in a
      concentration of about 10(-4) M reduced the level of TBA-active products.

PMID- 12227091
TI  - [Effect of bemethyl on the glutathione system in the rat liver in acute hypoxia].
AB  - The effect of bemithyl on the state of liver glutathione system was studied in
      rats under acute hypoxic hypoxia conditions modeled by "elevating" animals in a
      pressure chamber up to an altitude of 8000-11,000 m for 30 min. Bemithyl (25
      mg/kg, i.p.) administered 30 min before the hypoxia onset, prevents a decrease in
      the content of reduced glutathione and SH groups and impedes a drop in the
      activity of glutathione reductase and glutathione peroxidase. By means of the
      inhibition analysis using actinomycin D (a protein synthesis inhibitor), it was
      established that the protective action of bemithyl is related to the ability of
      enhancing the synthesis of antioxidant enzymes in the liver glutathione system.

PMID- 12227092
TI  - [Effect of a drug composition containing pyroglutamic acid and pyrrolidone on the
      cerebral circulation].
AB  - A drug composition containing pyroglutamic acid and pyrrolidone produces a
      significant effect on the cerebral circulation in rats and cats, which is
      manifested by increased cerebral blood flow and by a dose-independent improvement
      of the microcirculation. The cerebrovascular effects were similarly pronounced in
      both rats and cats which indicates that the drug action is independent of the
      animal species. The drug combination studied did not exhibit antiserotonin
      activity. The data obtained show evidence of a substantial contribution of the
      cerebrovascular component to the neuroprotector action of the drug composition
      studied.

PMID- 12227093
TI  - [Effect of bemethyl on cytochrome P-450-dependent monoxygenases in the human
      liver and lymphocytes].
AB  - Effects of the actoprotector bemithyl (50 mg/kg, p.o.) upon a single or five-fold
      administration on the cytochrome P-450 and b5 content and the isoform-specific
      and nonspecific monooxygenase activity [aminopyrine-N-demethylase, aniline-p
      hydroxylase, 4-nitroanisole-o-demethylase,2,5-diphenyloxazole-p-hydroxylase, 7
      ethoxyresorufin-o-deethylase (EROD), benzyloxyresorufin-o-debenzylase (BROD)] in
      rat liver were evaluated. In addition, the influence of bemithyl (0.(1)-100
      microM) on the development of EROD and BROD activity was studied on the mitogen
      stimulated human lymphocytes in vitro. Administered in rats, bemithyl exhibited
      the properties of a cytochrome P-450 inductor of the mixed type, which was
      manifested by an increase in the total cytochrome P-450 content in liver
      microsomes and in the monooxygenase activity related to both Ah-receptor
      dependent and -independent isoforms (except for the aniline-p-hydroxylase
      activity). The induction of the monooxygenase activity realized by Ah-receptor
      dependent isoforms (4-nitroanisole-o-demethylase, 2,5-diphenyloxazole-p
      hydroxylase, and EROD activity) was more pronounced, reaching maximum upon a
      single drug administration. Acting upon the human lymphocytes in vitro, high
      concentrations of bemithyl increased expression of the EROD activity, while low
      drug concentrations stimulated the BROD activity.

PMID- 12227094
TI  - [Immune and metabolic effects of carnitine and biotin in hemolytic anemia].
AB  - Single (80 mg/kg) or multiple (3 mg/kg) intramuscular introduction of
      phenylhydrazine decreases the functional activity of mononuclear blood cells and
      the immunological reactivity of the organism. Carnitine and biotin do not
      significantly influence the immunological response to a single administration of
      phenylhydrazine but noticeably reduce the expression of changes produced by
      repeated injections of the hemolytic toxin.

PMID- 12227095
TI  - [Xymedon decreases phosphatidylserine membrane expression induced by
      proapoptogenic deficit of serum growth factors in Jurkat T-cells].
AB  - The effect of xymedone, a non-glucoside analog of pyridine nucleosides, on the
      apoptosis of human CD4+ T cells of the Jurkat line was studied by laser flow
      cytometry method. Xymedone decreased the membrane expression of
      phosphatidylserine and suppressed the increase in permeability of the cytoplasmic
      membrane, thus inhibiting the onset of a degradation stage of the apoptotic
      cascade. Possible mechanisms of the antiapoptogenic effect of xymedone within the
      framework of a (cytochrome C/caspase 3)-dependent signal pathway of the apoptosis
      are discussed.

PMID- 12227096
TI  - [Immune mechanisms of hepatoprotector effects of etomersol and thymogen].
AB  - The reparation-regeneration effects of the actoprotector etomerzol and the
      immunomodulant thymogen can be mediated by certain units of the immune system, in
      particular, by thymus. Both thymogen and etomerzol loss the hepatoprotector
      activity on the background of thymectomy, but still produce an immunomodulant
      effect by stimulating the production of antibody-forming cells in the spleen in
      response to changes in the immune system induced by various stressor factors
      (thymectomy, hepatectomy, or their combination). This property of etomerzol,
      together with the absence of influence upon the immune state of intact
      experimental animals, is evidence of a dominating immunomodulant activity of this
      drug.

PMID- 12227097
TI  - [Effects of complexes of alpha-fetoprotein and amphiphilic docosaenoic acid
      derivatives on the humoral immune response in C57BL/6 mice].
AB  - The immunotropic activity of three derivatives of docosahexaenic acid (N
      docosahexaenoyl-L-serine phosphate, N-docosahexaenoyl-L-threonine phosphate, and
      N-docosahexaenoyl-L-tyrosine phosphate) in complexes with high-purity human alpha
      fetoprotein was evaluated. The polyene compounds stimulate the humoral immunity
      in mice immunized with T-dependent antigen (ram red blood cells). The
      immunotropic activity of the alpha-fetoprotein-ligand complexes studied depends
      on the structure and the content of polyene ligands.

PMID- 12227098
TI  - [Immunomodulating effects of carbohydrate and lipid metabolism activators in
      acute cold stress].
AB  - Joint injection of the activators of carbohydrate (thiamine, riboxin) and lipid
      (carnitin, biotin) metabolism in pairs reduces the expression of the decrease of
      the functional-metabolic activity of blood leukocytes and the inhibition of the
      immunological reactivity of organism, caused by air and immersion cooling. The
      most expressed immunomodulative effect is caused by the joint injection of
      thiamine and biotin.

PMID- 12227099
TI  - [Antimutagenic hypoxen activity in vivo].
AB  - The antimutagen effect of the drug hypoxen, representing poly(2,5
      dihydroxyphenylene)-4-thiosulfonic acid sodium salt, was studied by chromosome
      aberration assay in the bone marrow cells of C57BL/6 mice. Hypoxen (20 mg/kg,
      i.p.) administered simultaneously with dioxidine (300 mg/kg, i.p.) reduced
      genotoxicity of the latter compound by 35% over a time period of 24 h.
      Preliminary five-day administration of hypoxen (70 mg/kg, p.o.) did not decrease
      the dioxidine damage. The genoprotector activity of hypoxen upon interaperitoneal
      injection is more pronounced as compared to that of the reference drug sladex
      (aspartam).

PMID- 12227100
TI  - [Pharmacokinetic properties of rithmidazole upon single intravenous
      introduction].
AB  - The kinetics of rithmidazole (an imidazobenzimiodazole derivative possessing the
      properties of I, III, and IV class antiarrhythmics) was studied upon a single
      intravenous introduction in rats (in a dose of 10 mg/kg) and in healthy male
      volunteers (300 mg/kg). The drug pharmacokinetics in rat blood plasma was
      characterized by rapid elimination from the systemic blood flow (drug detected by
      HPLC only within 6 h); the total plasma clearance was 1.43 liter/(h kg), the
      terminal half-elimination time was 1.76 h, and the equilibrium distribution
      volume (2.42 liter/kg) exceeded the total volume of water in the animal organism,
      which is indicative of a high level of absorption in tissues. The drug is
      characterized by a low level of binding to blood proteins and erythrocytes.
      Investigation of the drug distribution between tissues showed evidence of
      extensive, blood-flow-dependent penetration, with the drug concentration in most
      tissues exceeding that in the blood plasma. The maximum amounts of rithmidazole
      were found in the lungs, spleen, liver, and kidneys. The major excretion route
      for the unchanged drug is via urine and bile, amounting to 10% and approximately
      1% of the dose introduced, respectively, determined within 72 h. The results are
      indicative of a low probability of the hepatoduodenal circulation of the
      unchanged substance: about 90% of the drug undergo metabolic transformation. The
      pharmacokinetics of rithmidazole in volunteers was also characterized by rapid
      elimination from the systemic blood flow; the total plasma clearance was 0.89
      liter/(h kg), the terminal half-elimination time was 2.12 h, and the equilibrium
      distribution volume was 1.66 liter/kg. The obtained results show that the
      pharmacokinetic profiles of rithmidazole in rats and humans exhibit a similar
      character, with a high intensity of distribution and elimination processes.

PMID- 12227101
TI  - [Anandamide and R-(+)-methanandamide prevent development of ischemic and
      reperfusion arrhythmia in rats by stimulation of CB2-receptors].
AB  - It has been found that prior intravenous administration of the endocannabinoid
      anandamide (10 mg/kg) or its synthetic analogue R-(+)-methanadamide (5 mg/kg)
      prevents a development of ischemic and reperfusion arrhythmias in rats. The prior
      injection of the CB1 receptor antagonist, SR 141716A (3 mg/kg), did no affect the
      antiarrhythmic action of both cannabinoids. Pretreatment with the CB2 receptor
      antagonist, SR 144528 (1 mg/kg), completely abolished antiarrhythmic effect of
      anandamide and R-(+)-methanandamide. Both CB antagonist had no effect on the
      arrhythmias itself. Pretreatment with the NO-synthase inhibitor, L-NAME (50
      mg/kg), had no effect on the antiarrhythmic action of cannabinoids. We therefore
      conclude that CB2 receptor stimulation increases the heart tolerance to ischemic
      and reperfusion arrhythmias.

PMID- 12227102
TI  - [Preclinical toxicologic study of a Baikal aconite tincture (bayacon)].
AB  - The safety of bayacon, a new drug based on Baikal aconite intended for the
      treatment of inflammation-proliferative dermatitis (psoriasis), was studied on a
      preclinical level. With respect to a single introduction in rats and mice, the
      drug is classified as a low-toxicity substance. However, a 3-month oral
      administration of bayacon (0.25, 0.5, and 2.5 mg/kg) in rats showed a number of
      dose-dependent functional and morphological changes. A dose of 2.5 mg/kg induced
      weak hyporegenerative anemia, neutrophile leukocytosis, and dystrophic changes in
      the stomach mucosa, heart, liver, and kidneys. All these symptoms disappeared
      within two weeks after abolition of the drug. Oral administration of bayacon (0.1
      and 0.5 mg/kg) in rabbits produced no pathological morphofunctional changes in
      the organs and tissues studied. In rats, bayacon 2.5, 0.5, and 0.25 mg/kg doses
      of bayacon led to dose-dependent changes in some characteristics of the
      reproduction system. The drug did not influence the expression of allergic
      reactions and showed no immunotoxicity and mutagenicity manifestations.

PMID- 12227103
TI  - [Pharmacological properties od steroid glycosides from Ruscus ponticus].
AB  - Some pharmacological properties of the sum of steroidal glycosides (ruscoponin
      preparation) extracted from underground parts of Ruscus ponticus were studied.
      The drug exhibits a pronounced antiexudative effect (related to the alpha 1
      adrenergic activity) on the models of formalin edema and pouch granuloma in rats
      and a thermal rectum inflammation in mice. The drug exhibited no hepato-, nephro
      , and gastrotoxicity.

PMID- 12227104
TI  - [Laboratory and clinical study of therapeutic efficacy of medicinal films for
      surgical procedures].
AB  - An analysis of the experimental data showed that anesthetic medicinal films
      (AMFs) offer an effective medicinal form for the treatment of suppurative
      inflammatory disorders(SIDs) of soft tissues. The results of preclinical
      experiments with AMFs showed evidence of anesthetic, antimicrobial, and
      hemostatic effects. The therapeutic effect was established in the course of
      clinical investigations and confirmed by the results of cytological,
      histological, morphological, and bacteriological testing. The experimental data
      indicate that AMF application offers a promising means of SID treatment. Further
      development of this medicinal form must lead to an increase in the therapeutic
      efficacy, decrease the drug dose, and reduce the probability of side effects
      during the treatment of SIDs in soft tissues of various localization.

PMID- 12227105
TI  - [Chronic alcoholization and GABA-ergic system].

PMID- 12227106
TI  - [September 11 from the viewpoint of a Swiss trauma fellow in New York].
AB  - This is the report of the events of September 11th seen through the eyes of a
      Swiss Trauma Fellow. This ill-fated day is described by someone who went down to
      ground zero with other doctors to help and save lives and came back frustrated
      because there was so little to be done.

PMID- 12227108
TI  - Intracranial subdural empyema and its management. A review of the literature with
      comment.
AB  - Intracranial subdural empyema is a rare form of suppuration in Europe and North
      America, and is a potentially dangerous but treatable disease. The clinician must
      be aware that this complication requires prompt diagnosis and urgent
      neurosurgical intervention. The etiology, pathology, bacteriology, clinical
      features, diagnostic procedures and the different surgical approaches to this
      disease are reviewed. It seems that there is no single best surgical approach for
      treating subdural empyema, however, multiple burr holes drainage and craniotomy
      remain the most frequently used approaches.

PMID- 12227107
TI  - [Craniocerebral trauma--new pathophysiological and therapeutic viewpoints].
AB  - AIM: The prognosis has markedly improved during the last years after mild and
      moderate head injuries. After severe head trauma, this evolution could not be
      observed so far. This requires a better understanding of pathophysiological
      interaction, especially in the subacute and late phase of trauma. METHODS: Review
      article. DISCUSSION: Causes for the development of secondary brain damage are the
      intracranial space demand after traumatic injury and edema formation which max
      result in ischemia, as well as inflammatory processes. Both isolated severe head
      trauma and polytrauma with or without brain damage may result in a systemic
      inflammatory response syndrome due to the synthesis of cytokines and other
      inflammatory mediators which may cause a single or multiple organ failure. The
      hypermetabolism after severe head trauma is often regarded as an interaction
      between the central nervous system and the whole organism by the activation of
      the neuroendocrine axis. Moreover, coagulation, metabolism and fracture healing
      are influenced by the onset of SIRS as well. CONCLUSION: Our knowledge about the
      bidirectional inflammatory interaction between brain and whole organism is still
      limited. It is generally accepted that extracranial complications are highly
      influential in determining the outcome from severe head injury.

PMID- 12227109
TI  - The matrix metalloproteinase inhibitor batimastat inhibits the lung colonisation
      of orthotopically implanted malignant pancreatic tumor cells in SCID mice.
AB  - AIM OF STUDY: In this study, we investigated the effect of the matrix
      metalloproteinase inhibitor batimastat on the lung colonisation of orthotopically
      implanted malignant pancreatic tumor cells in SCID mice. MATERIAL AND METHODS:
      Following intraperitoneal anaesthesia, 10(6) Panc-TU-1 cells were orthotopically
      implanted in the head of the pancreas in 20 SCID mice. Seven days later,
      treatment of 10 of these mice with an intraperitoneal injection of batimastat (30
      mg/kg body weight) was begun and continued for 14 days. Of the mice in the
      untreated control group, 3 were sacrificed and examined after 7 days, a further 3
      after 14 days and the remainder together with the group that had been treated
      after 21 days. RESULTS: Tumor growth was clearly visible between the 14th. and
      the 21st. postoperative day. The orthotopically implanted tumor cells
      metastasized between the 2nd. and 3rd. postoperative week in the lung. In the
      control group, a diffuse metastasis of the lung was observed, but in the group of
      treated mice no lung metastases were found. CONCLUSION: In this mouse model, a
      clear reduction and inhibition of lung metastases from orthotopically implanted
      pancreatic tumor cells was achieved by treatment with the matrix
      metalloproteinase inhibitor batimastat.

PMID- 12227110
TI  - Present status of infrainguinal arterial bypass procedures following an all
      autogenous policy--long-term results of a single center.
AB  - OBJECTIVES: The direction of vein grafts for infrainguinal arterial
      reconstruction is controversial. Long-term results of a single center following
      an all autogenous tissue policy in infrainguinal arterial reconstruction are
      reported with special attention to possible advantages for the in situ and non
      reversed bypass using angioscopy. METHODS: From 10/88 until 12/00 540 bypasses
      with autogenous veins were performed on 497 patients. Veins were used in a non
      reversed or in-situ direction, valve disruption was performed under angioscopic
      control. All grafts were prospectively included in our data base and follow-up
      was scheduled in our vascular lab before discharge and after 3, 6, 9, 12, 24 etc.
      months. RESULTS: Primary patency of all bypasses after 108 months was 55.2%,
      primary assisted 76.9% (SE +/- 9.87), survival 58.4% (SE +/- 8.88) and limb
      salvage 81.3% (SE +/- 9.75). Perioperative mortality was 0.9% (5 pat). Patency
      rates (primary assisted patency) after 72 months were 81.7% (98.2%) for
      supragenicular, 61.5% (79.4%) for infragenicular and 56.6% (78.1%) for tibial
      anastomoses and for pedal reconstructions after 48 months 49.3% (68.6%).
      CONCLUSION: Reviewing the literature neither the in situ and non-reversed nor the
      reversed grafts yielded better long-term results. Absence of size mismatch may be
      an advantage in smaller veins. Angioscopy may detect unsuspected vein disease.

PMID- 12227111
TI  - [Effect of extracorporeal shockwave therapy on vascular regulation. Infrared
      thermography in epicondylitis humeri radialis].
AB  - BACKGROUND: Extracorporeal shockwave therapy (ESWT) is recommended as an
      alternative treatment for lateral epicondylitis (LE). An influence on the blood
      perfusion is considered to be one possible effect. Infrared thermography is used
      in this trial to measure effects of ESWT on the thermal regulation in the target
      area. METHODS: 33 patients with chronic LE were examined in a prospective,
      placebo-controlled single blind study with an independent observer. 3 x 2000
      impulses of an energy flux density ED+ 0.22 mJ/mm2 were applied under local
      anaesthesia as verum-ESWT. Placebo-ESWT was performed under the same conditions.
      One elbow was treated, the other served as control. Before and after each
      shockwave application and after 12 weeks skin temperature was measured on both
      elbows at three predefined points by infrared thermography. RESULTS: While a
      significant decrease in the skin temperature was found on the treated and sham
      treated sides opposed to the contralateral side, there was no difference between
      the real shockwave treatment and placebo therapy. Responder and Non-responder to
      the treatment could not be distinguished during the therapy. DISCUSSION: Infrared
      thermography was proved to be a valuable additional technical instrument for
      diagnosis of LE, but is not an appropriate instrument to predict the clinical
      outcome in patients treated with ESWT. A noted reduction of skin temperature on
      the treated side is not due to specific effects of the shockwaves. It is unlikely
      that ESWT as applied has an influence on thermal regulation in the target area.
      These findings are supported by negative results of experimental and clinical
      trials.

PMID- 12227112
TI  - [Experiences with endoscopic carpal tunnel release].
AB  - Between 1994 and 2000 122 open and endoscopic carpal tunnel releases were
      performed. 82 of them were analysed retrospectively with major interest in
      security and results of the endoscopic technique. 39 patients were treated with
      an open, 41 patients with an endoscopic carpal tunnel release (26 using the two
      portal technique, 17 using the single portal technique). No major irreversible
      complications were reported, regarding the outcome their were no significant
      differences. From the 39 patients with open carpal tunnel release nine had
      persistent complaints and one of them was reoperated because of an injury of the
      motoric branch of the median nerve. Eight patients out of 26 treated with the two
      portal technique still had complaints and one needed to be reoperated because of
      excessive fibrosis around the median nerve. From the 17 patients operated with
      the single portal technique five had persistent complaints but no reoperation was
      necessary. Our study showed similar findings regarding security and results using
      the three different operation methods. But there were no advantages for the
      endoscopic carpal tunnel release because of the more atraumatic procedure.

PMID- 12227113
TI  - [Treatment of proximal ulnar comminuted fractures--a challenge].
AB  - INTRODUCTION: Comminuted fractures of the proximal ulna are severe injuries often
      complicated by involvement of the elbow joint and damaged soft tissues. The
      treatment of these fractures is very demanding and the results often mediocre due
      to of ancillary injuries (Dislocation in the humero-ulnar joint and associated
      radial head fractures). We analyzed the results of the treatment of these
      fractures and investigated whether other factors than the severity of fracture
      type influenced the final outcome. METHOD: Retrospective analysis of 18 patients
      with comminuted proximal ulna fractures. These comminuted ulna fractures included
      not only C-fractures according the the AO classification but also A1, A3, B1 and
      B3 fractures. Postoperative clinical and radiological examinations were routinely
      performed at 1/2-1 year intervals following treatment according to bone healing
      and work begin. This was done up to 48 months following treatment. Elbow function
      was recorded one year after the accident using the Morrey score. RESULTS:
      According the the AO classification, of the total of 18 patients, four suffered
      from an A-fracture, four from a B-fracture and 10 from a C-fracture. Eight of the
      18 patients had an open fracture. 10/18 of the patients also had a fractured
      radial head and 9/18 of the cases had a dislocation of the humero-ulnar joint.
      The average range of motion based on a postoperative examination after one year
      was extension/flexion 0 degree/20 degrees/120 degrees and pronation/supination 70
      degrees/0 degree/70 degrees. The assessment based on the Morrey-score indicated
      excellent to good results for 10 patients, average results for four patients and
      poor results for four patients. CONCLUSION: Despite correct diagnosis of the
      severity of injury and adequate treatment the results are only mediocre due to
      associated injuries (dislocation, radial head fractures). The goal is a stable
      anatomic reconstruction to allow early functional treatment.

PMID- 12227114
TI  - [Hemilithotomy position for intramedullary nailing of the femur and compartment
      syndrome of the healthy leg].
AB  - The well leg compartment Syndrome following long procedures in the dorsal
      lithotomy or hemi-lithotomy position is a rare complication. Its diagnosis is
      usually late and the neurological deficit are often permanent. We report two
      cases of femoral nailing complicated by Compartment Syndrome of the contralateral
      leg. We review the published literature on 40 cases which suggests a clear
      relationship between these positions, the duration of the intervention and the
      degree of leg elevation. Given the potentially severe sequel, prevention is a
      must and a high degree of suspicion is the key to an early diagnosis. A modified
      hemi-lithotomy position is proposed. That avoids extreme elevation of the leg and
      diminishes the hip and knee flexion required while allowing adequate fluoroscopy.

PMID- 12227115
TI  - [Apparent pseudarthrosis of the thumb].
AB  - Pseudarthrosis in the hand are defined as a non-union of a fracture after 6
      month. Reasons might be biological disorders, mechanical instability or infection
      after fracture treatment. Pseudoarthrotic bone demands stable osteosynthesis and
      often bone grafting. The presented case is about a dislocated osseous fragment
      attached to the Aponeurosis dorsalis mimicking clinical and radiological a
      Pseudarthrosis of the proximal phalanx of the thumb. We would like to draw
      attention that osseous fragments may present very similarly to a pseudoarthrosis
      of a phalanx.

PMID- 12227116
TI  - What is evidence-based medicine?
AB  - Evidence-based practice requires clinical expertise, common sense, understanding
      of the circumstances and values of the patient, and judicious application of the
      best available evidence. This article discusses evidence-based medicine as an
      explicit and formal problem-solving strategy.

PMID- 12227117
TI  - Evidence-based endocrinology. Finding the current best research evidence for
      practice in endocrinology.
AB  - New medical information is accumulating at an astonishing rate. It is available
      in many forms and flavors, and information seekers benefit from being
      discriminating in searches for answers to clinical problems. Few problems can be
      addressed satisfactorily simply by entering some relevant content terms into
      Medline. Such a search, unless the problem is rare, usually results in a flood of
      citations with no arrangement according to quality, and the user must determine
      painstakingly which citations are relevant and clinically useful. Fortunately,
      evidence-based information services are catching up with the growth of the
      medical literature. Such services organize and provide access to the current best
      evidence at the point of need. We have described a "4 S" hierarchy of evidence
      based resources to help focus a practitioner's information seeking strategies,
      with systems at the highest level of organization, followed by synopses,
      syntheses, and studies. Practitioners should become familiar with the best access
      routes for regularly updated services of relevance to their interests and direct
      their inquiries initially to the highest level of organization of information
      that exists for their interests. Evidence-based resources continue to be created
      and evolve, so keeping an eye out for new resources and examining their pedigrees
      according to the "4 S" approach permit practitioners to assemble and organize an
      ever-improving personal evidence-based library for endocrinology.

PMID- 12227118
TI  - Epidemiologic analyses of risk factors, risk indicators, risk markers, and causal
      factors. The example of albuminuria and the risk of cardiovascular disease in
      diabetes.
AB  - Much of the practice of modern medicine deals with prevention of the consequences
      of chronic conditions, including diabetes, hypertension, obesity, asthma, chronic
      bronchitis, and inflammatory bowel diseases. To achieve this end, identifying
      people at risk for these consequences and then initiating the appropriate,
      evidence-based preventive therapies are key. Characterization and study of risk
      factors are at the core of this effort and represent the only way that high-risk
      individuals can be identified. These risk factors can be any imagined variable,
      ranging from a genetic mutation to a blood result, a previous disease, exposure
      to an infectious agent or toxin, a socioeconomic state, ethnicity, birth weight,
      or country of origin. All causal factors for an outcome are risk factors for that
      outcome; reducing these risk factors almost certainly reduces the outcome. The
      converse is usually not true, however: identification of a risk factor reveals
      little about its causal connection to the outcome in question, and reducing this
      risk factor may or may not reduce the outcome. Once high-risk individuals are
      identified on the basis of their risk factor profile, the relevant clinical
      question relates to which therapies have been identified clearly that will reduce
      the risk or the outcome. If modification of the level of the risk factor is
      considered therapeutically, the question of whether the risk factor is also a
      good surrogate outcome must be answered. Information regarding whether the risk
      factor causes the disease is highly desirable; however, it is often unavailable
      and is not required before making therapeutic decisions.

PMID- 12227119
TI  - Establishing the role of gene-environment interactions in the etiology of type 2
      diabetes.
AB  - The descriptive epidemiology of type 2 diabetes and findings from cohort studies
      suggest that this disorder originates in large part from a complex interaction
      between genetic and environmental factors. Determining the details of these
      interactions using the nested case-control design may be optimal, but is a long
      term and expensive strategy. Quicker and cheaper results may be obtained by
      studying interaction on the quantitative traits that underlie diabetes; however,
      the power of such studies to detect interaction is highly dependent on the
      precision with which non-genetic exposures are measured. Unraveling these
      interactions will undoubtedly shed light on the etiology of diabetes and will, we
      hope, lead to opportunities for targeted prevention. Recent studies in high-risk
      groups such as people with impaired glucose tolerance suggest that the incidence
      of diabetes can be reduced by more than 50% by interventions aimed at changing
      dietary and physical activity behavior [39,40]; however, it may be that
      individuals with a particular genotype are particularly susceptible to the
      negative metabolic consequences of sedentary living, and that they conversely,
      therefore, would have most to gain from a targeted preventive intervention
      program. Understanding how to detect these individuals and which environmental
      factors a program should attempt to manipulate is a major goal of studies that
      attempt to unravel gene-environment interaction.

PMID- 12227120
TI  - Evidence-based diagnosis in endocrinology.
AB  - In this article we present factors that determine whether one can trust the
      results of studies that describe the properties of diagnostic tests. We review
      the ways in which the results of such studies could be presented to the readers
      and consider factors that determine the value of such reports in one's own
      clinical practice.

PMID- 12227121
TI  - Integrating qualitative research into evidence based practice.
AB  - This article attempts to provide an overview of qualitative tools and methods
      using mainly examples from diabetes research. The other articles in this issue of
      the Endocrinology and Metabolism Clinics of North America have demonstrated the
      enormous contribution made in the past 15 years or so by rigorous quantitative
      studies of prevalence, diagnosis, prognosis, and therapy to clinical decision
      making in endocrinology. In the early 21st century, the state of qualitative
      research into such topics as the illness experience of diabetes; the barriers to
      effective self care and positive health choices; the design of complex
      educational interventions; the design of appropriate, acceptable and responsive
      health services; and the decision-making behavior of health professionals, is
      such that there remain many more questions than answers. But qualitative research
      is increasingly recognized as an important, legitimate and expanding dimension of
      evidence-based health care (18;19). It is highly likely that the major landmark
      studies in diabetes care over the next decade will build on an exploratory
      qualitative study or incorporate an explanatory or evaluative dimension based on
      qualitative methods.

PMID- 12227122
TI  - Using evidence in practice. Foot care in diabetes.
AB  - Foot ulceration and amputation remain all too common complications for people
      with diabetes mellitus. Overcoming this, however, requires considerable effort.
      Improved implementation of patient education programs is essential, along with
      increased access to resources to support optimal foot care and the acquisition of
      optimal footwear for patients at highest risk of these complications. Well
      coordinated screening programs are likely to be highly beneficial.
      Multidisciplinary care must be available for patients with established lower
      extremity disease. Equally important, further research into foot ulcer prevention
      and management is critical. The total number of studies completed to date in the
      field remains low, especially considering the frequency and devastating nature of
      lower extremity complications.

PMID- 12227123
TI  - Systematic reviews in endocrinology. The Cochrane Metabolism and Endocrine
      Disorders Review Group.
AB  - The Cochrane Collaboration is an international nonprofit organization that aims
      to make up-to-date accurate information about the effects of health care readily
      available worldwide by preparing, maintaining, and disseminating systematic
      reviews of the effects of health care. The Cochrane Metabolism, Endocrinology,
      and Diabetes Review Group's primary concern is the evaluation of randomized
      controlled trials and other controlled comparisons of health care interventions
      relevant to the prevention, treatment or management, and rehabilitation of
      metabolic, nutritional, and endocrine disorders. This article discusses the role
      of systematic reviews and metaanalyses and invites interested parties to get
      involved and contribute.

PMID- 12227124
TI  - Use of plasma aldosterone concentration-to-plasma renin activity ratio as a
      screening test for primary aldosteronism. A systematic review of the literature.
AB  - The aldosterone-renin ratio is widely used to screen for primary aldosteronism.
      We conducted a systematic review of the literature to establish the test
      characteristics (sensitivity, specificity, likelihood ratios at different cutoff
      values) of the aldosterone-renin ratio used in screening for primary
      aldosteronism in subjects with presumed essential hypertension. We searched
      Medline, EMBASE, and Current Contents databases, bibliographies of retrieved
      papers, and personal files for all reports published from January 1966 to October
      2001. We consulted experts to identify additional published and unpublished
      reports. We included prospective studies of the ratio as a screening test for
      primary aldosteronism, without applying language or data availability
      restrictions. We excluded retrospective studies, case reports, and duplicate or
      preliminary reports. Working independently, we selected the articles, assessed
      their quality, and extracted their data. Data extracted included sample size and
      care setting, description of the testing conditions, description of the
      confirmatory tests, and the test characteristics of the ratio (sensitivity,
      specificity, likelihood ratios at different cutoff values). This review includes
      16 studies with 3136 participants. None of the studies evaluated the aldosterone
      renin ratio and the reference standard independently of each other; only two
      studies evaluated patients who had a "negative" ratio with the reference
      standard. Only 16.7% of the subjects had both the ratio and the confirmatory test
      performed. Ratio cutoff values ranged from 200 to 2774 pmol/L per ng/mL per hour.
      None of the studies provided valid estimates of the aldosterone-renin ratio test
      characteristics. There are no published valid estimates of the test
      characteristics of the aldosterone-renin ratio when used as a screening test for
      primary aldosteronism in patients with presumed essential hypertension.

PMID- 12227125
TI  - Patient education for preventing diabetic foot ulceration. A systematic review.
AB  - OBJECTIVE: Ulceration of the feet, which can result in loss of limbs and death,
      is a major health problem for people with diabetes mellitus. The objective of
      this review is to assess the effectiveness of patient education to prevent
      diabetic foot ulcers. RESEARCH DESIGN AND METHODS: We conducted a systematic
      review of randomized controlled trials (RCTs) that evaluated educational
      programmes for the prevention of foot ulcers in people with diabetes mellitus. We
      used standard search methods of the Cochrane "Wounds Groups". Two reviewers
      working independently extracted data and assessed study quality. RESULTS: The
      methodologic quality of the 8 included RCTs was poor. The internal validity score
      (range 0-10) of individual RCTs ranged from 2 to 4. Four trials compared the
      effect of intensive with brief educational interventions; 2 of these reported
      clinical endpoints. One study involving high-risk patients reported a reduction
      in ulcer incidence (OR 0.28, 95% confidence interval [CI] 0.13-0.59) and
      amputation rate (OR 0.32, 95% CI 0.14-0.71) after 1 year. The other RCT did not
      find an effect after 7 years of follow-up. Two trials showed that participants'
      foot care knowledge significantly improved with education. In one trial, foot
      care knowledge was significantly worse at 6 months, although foot care behavior
      improved significantly. One RCT, that compared patient foot care education as
      part of a general diabetes education program to usual care, showed no reduction
      in the risk of foot ulceration. In one RCT, patient education as part of a
      complex intervention targeted at both people with diabetes and doctors reduced
      the prevalence of serious foot lesions at 1 year (OR 0.41, 95% CI 0.16-1.00) and
      improved foot care behavior. Evidence from two RCTs comparing the effect of
      patient-tailored education in addition to usual care was conflicting. SUMMARY:
      Evidence, limited by poor methodologic quality and conflicting results, suggests
      that patient education may have positive but short-lived effects on foot care
      knowledge and behavior of patients and may reduce foot ulceration and
      amputations, especially in high-risk patients. High-quality randomized controlled
      trials are needed to establish the efficacy of patient education to prevent
      diabetic foot ulcerations.

PMID- 12227126
TI  - Summary of meta-analyses of therapies for postmenopausal osteoporosis and the
      relationship between bone density and fractures.
AB  - We review the methodologic quality of the individual randomized trials and
      summarize the impact of different treatments on the risk of fractures and bone
      density. We present an estimate of the expected impact of anti-osteoporosis
      interventions on fracture incidence in prevention and treatment populations using
      numbers needed to treat. We also examine the relationship between changes in bone
      density and the relative risk reduction for vertebral and nonvertebral fractures
      using regression analyses drawn from the results of the systematic reviews. We
      also outline other important facets of the decision-making process regarding
      osteoporosis therapy, including attitudes toward uncertainty, circumstances, and
      patients' and societal preferences.

PMID- 12227127
TI  - Iodized salt for iodine deficiency disorders. A systematic review.
AB  - The results suggest that iodized salt is an effective means of improving iodine
      status, and support the current endeavors to achieve universal salt iodization.
      Variations in the iodine levels in the salt suggest that particular care must be
      taken to ensure the quality of the production and storage of iodized salt. It
      appears that in small children salt intake may not be high enough to guarantee
      adequate iodine levels through the use of iodized salt. While the studies
      provided no information about unwanted side effects with the use of iodized salt,
      most studies did not specifically consider adverse effects. so inferences about
      side effects remain weak. In conclusion, health policymakers and other decision
      makers require high-quality studies to measure the effect of iodized salt in
      comparison with other forms of iodine supplementation. These should be large
      studies lasting at least two years. Investigators should not retstrict their
      outcomes to goiter rates and urinary iodine excretion, but should include the
      other outcome measures specified above, such as mental and physical development
      in children, mortality, and others. Investigators should pay special attention to
      adverse effects and their report in primary studies, and should assess children
      (including very young children who may have a relatively low salt consumption)
      separately from adults.

PMID- 12227128
TI  - Pharmacotherapy for thyroid nodules. A systematic review and meta-analysis.
AB  - The review highlights the uncertainty in the management of nodular thyroid
      disease. Thyroxine suppressive treatment is given in the hope that nodules might
      decrease in size, sometimes assuming that dependency on TSH is different in
      benign and malignant nodular disease. Follow-up of benign nodules over 10 years
      suggested that most remain the same, shrink, or disappear [14]. TSH suppression
      may lead to hyperthyroidism, reduced bone density [37.39], and atrial
      fibrilation; however, apart from reduction of nodule size or arrest in nodule
      growth, thyroxine therapy may benefit patients by reducing perinodular volume.
      Consequently, both pressure symptoms and cosmetic complaints could improve.
      Unfortunately, no information concerning symptoms or well-being is available from
      published randomized trials. In conclusion, more high quality studies of
      sufficient duration with adequate power estimation are needed. Uncertainty about
      predictors of response or the impact on outcomes that are important to patients
      leaves considerable doubt about the wisdom of applying suppressive therapy.
      Future studies shoudl include patient-important outcomes including thyroid cancer
      incidence, health-related quality of life and costs.

PMID- 12227129
TI  - Human versus animal insulin in people with diabetes mellitus. A systematic
      review.
AB  - This review is in accordance with the findings of the systematic review of Airey
      et al [18] with respect to the absence of a differential effect on hypoglycemia
      between human and animal insulin. For the first time, however, the review
      compares the relative efficacies of human and animal insulin, which indicates
      that human insulin was introduced without proof of being superior to animal
      insulin. Studies have not assessed patient-centered outcomes [41,42], such as
      patient satisfaction, health-related quality of life, and diabetes-related
      morbidity. Randomized trials did not report on qualitative assessments of
      patients' experiences when using different insulin species. Because history tends
      to repeat itself, we probably will be faced with other "innovations" (e.g.,
      insulin analogs) evaluated in clinical trials tht focus on surrogate outcomes
      followed by marketing of insulins "proved" to be effective in short-term,
      underpowered, and badly executed studies.

PMID- 12227130
TI  - Glucocorticoid withdrawal schemes in chronic medical disorders. A systematic
      review.
AB  - This systematic review highlights the uncertainty about the safety and efficacy
      of glucocorticoid withdrawal in many chronic diseases, elucidating the need for
      further research in this area. The problem of glucocorticoid withdrawal seems to
      be good example for wide variation in physicians' approaches to weaning patients
      off glucocorticoids. This practice variation appears justified, given the well
      known extraordinary array of individual reactions to systemic glucocorticoid
      therapy [44], the obligation to individualize treatment, and scientific
      uncertainty. Moreover, only sparse information concerning health-related quality
      of life, well-being and symptoms, and socioeconomic sequelae after glucocorticoid
      withdrawal is available from published randomized trials. In conclusion,
      clinicians and patients need many more--and in a number of conditions, initial-
      high quality studies to assess the safety and efficacy of systemic glucocorticoid
      withdrawal schedules in chronic diseases.

PMID- 12227131
TI  - Aspirin in diabetic retinopathy. A systematic review.
AB  - Diabetes mellitus is a risk factor for eye disease that can lead to blindness.
      There have been both concerns that aspirin use might worsen diabetic retinopathy,
      as well as hopes that aspirin might be beneficial in treating it. We investigated
      whether there are beneficial effects of aspirin alone and in combination with
      other antiplatelet agents in the treatment of diabetic retinopathy, and the
      relative hazards for the development of high-risk proliferative retinopathy
      following aspirin treatment. We conducted a sensitive search for randomized
      controlled trials combined with index terms for identifying studies on aspirin
      treatment in diabetic retinopathy in the Cochrane Library (issue 4, 2001) and
      Medline (1966 to October, 2001). We examined randomized controlled clinical
      trials in diabetic patients with (non) proliferative diabetic retinopathy and
      aspirin treatment alone or in combination with dipyramidole versus placebo
      administration. Two independent reviewers judged trial eligibility, collected
      details of study population, interventions, and outcomes using a standard data
      extraction form. One reviewer assessed the quality of trial reporting. We
      identified six publications pertinent to our objective. Aspirin dosages ranged
      from 650 mg to 990 mg daily, the dose of dipyridamole, used in only one trial,
      was 225 mg per day. Studies lasted 8 weeks to 5 years. All trials showed that
      aspirin alone or in combination with dipyridamole neither lowered nor increased
      the risk of the development of diabetic retinopathy. The results suggest that
      there are no ocular contraindications to taking aspirin if required as part of a
      treatment for cardiovascular diseases or other medical indications.

PMID- 12227132
TI  - Development and use of evidence-based clinical practice guidelines for thyroid
      disease.
AB  - Clinical practice guidelines offer recommendations for optimizing health care.
      Guideline panels can rely on several methods for gathering information about
      current practice and synthesizing evidence that addresses specific questions.
      Clinical practice guidelines, including many that address thyroid disease, often
      rely on conventional narrative literature reviews and expert opinion rather than
      systematic evaluation of the published literature as the basis for their
      recommendations. This undermines the authority of practice guidelines and
      potentially results in disparate, invalid, or misleading recommendations. In
      contrast, incorporation of rigorous systematic reviews of literature and guidance
      by groups with multidisciplinary expertise decreases bias in evidence selection
      and increases precision of treatment effect estimates. Improved reliability and
      accuracy of evidence assessment, in turn, strengthens ultimate guideline
      recommendations. Cost-effective analyses further contribute to useful clinical
      practice guidelines and may encourage the explicit acknowledgment of values and
      preferences. Valid recommendations, however, prove futile in the absence of
      implementation. Adherence to guidelines may be improved with integration of user
      friendly computer applications into clinical practice. By overcoming barriers to
      implementation and addressing the limitations of current guidelines,
      endocrinologists can play an essential role in improving the quality, efficiency,
      and cost-effectiveness of clinical practice related to thyroid disorders.

PMID- 12227134
TI  - ELI's coming!

PMID- 12227133
TI  - Adherence of published diabetes mellitus practice guidelines to methodologic
      standards of guideline development.
AB  - There are multiple practice guidelines published pertaining to diabetes care.
      Experts have formulated methodologic standards of guideline formulation. To
      determine whether practice guidelines pertaining to diabetes and published in
      peer-reviewed publications and the Internet adhered to established methodologic
      standards of guideline development. We identified all guidelines pertaining to
      diabetes care published between 1980 and 2000 using a computerized search of
      Medline, the Practice Guidelines Clearinghouse, the Institute for Clinical
      Systems Improvement Web site, and a global internet search engine. We used a
      previously validated 25-item assessment tool to determine guideline adherence to
      methodologic standards in three categories: guideline development and format,
      identification and summary of evidence, and formulation of recommendations. We
      conducted a multivariable regression analysis to determine the influence of
      guideline author, publishing medium, year of publication, and guidelines length
      on adherence to methodologic standards of guideline development. We evaluated 43
      guidelines: 33% published on the Internet, 66% in peer-reviewed journals; 51%
      published by organizations, and 49% by individual experts. Of a maximum of 25
      methodologic standards, the number of standards adhered by a guideline was 9
      (range, 2 to 19). Mean proportion (SD) of guidelines that adhered to methodologic
      standards on guideline development and format was 48% (28); on identification and
      summary of evidence, 21% (22); and on the formulation of recommendations, 36%
      (27). Longer guidelines had greater adherence to methodologic standards (P <
      0.0001). Guidelines pertaining to diabetes care published on the internet and in
      peer-reviewed publications do not meet most methodologic standards of guideline
      development.

PMID- 12227135
TI  - OPL--small blessings.

PMID- 12227136
TI  - Considerations for EFTS. Members maintaining a routing table in DOCLINE 1.3.

PMID- 12227137
TI  - Benchmarking implementation task force. Conference report.

PMID- 12227138
TI  - Library exposure via HIPAA.

PMID- 12227139
TI  - Volunteers: even more valuable now.

PMID- 12227140
TI  - Is it legal?

PMID- 12227141
TI  - Death by a thousand cuts.

PMID- 12227142
TI  - Spoon-feeding the masses. Dishing it out a la librarian.

PMID- 12227143
TI  - What makes great boards great.
AB  - In the wake of meltdowns at WorldCom, Tyco, and Enron, enormous attention has
      been focused on the companies' boards. It seems inconceivable that business
      disasters of such magnitude could happen without gross or even criminal
      negligence on the part of board members. And yet a close examination of those
      boards reveals no broad pattern of incompetence or corruption. In fact, they
      followed most of the accepted standards for board operations: Members showed up
      for meetings; they had money invested in the company; audit committees,
      compensation committees, and codes of ethics were in place; the boards weren't
      too small or too big, nor were they dominated by insiders. In other words, they
      passed the tests that would normally be applied to determine whether a board of
      directors was likely to do a good job. And that's precisely what's so scary,
      according to corporate governance expert Jeffrey Sonnenfeld, who suggests that
      it's time for some new thinking about how corporate boards operate and are
      evaluated. He proposes thinking not only about how to structure the board's work
      but also about how to manage it as a social system. Good boards are, very simply,
      high-functioning work groups. They're distinguished by a climate of respect,
      trust, and candor among board members and between the board and management.
      Information is shared openly and on time; emergent political factions are quickly
      eliminated. Members feel free to challenge one another's assumptions and
      conclusions, and management encourages lively discussion of strategic issues.
      Directors feel a responsibility to contribute meaningfully to the board's
      performance. In addition, good boards assess their own performance, both
      collectively and individually.

PMID- 12227144
TI  - A better way to deliver bad news.
AB  - In an ideal world, a subordinate would accept critical feedback from a manager
      with an open mind. He or she would ask a few clarifying questions, promise to
      work on certain performance areas, and show signs of improvement over time. But
      things don't always turn out that way. Such conversations can be unpleasant.
      Emotions can run high; tempers can flare. Fearing that the employee will become
      angry and defensive, the boss all too often inadvertently sabotages the meeting
      by preparing for it in a way that stifles honest discussion. This unintentional-
      indeed, unconscious--stress-induced habit makes it difficult to deliver
      corrective feedback effectively. Insead professor Jean-Francois Manzoni says that
      by changing the mind-set with which they develop and deliver negative feedback,
      managers can increase their odds of having productive conversations without
      damaging relationships. Manzoni describes two behavioral phenomena that color the
      feedback process--the fundamental attribution error and the false consensus
      effect--and uses real-world examples to demonstrate how bosses' critiques can go
      astray. Managers tend to frame difficult situations and decisions in a way that
      is narrow (alternatives aren't considered) and binary (there are only two
      possible outcomes--win or lose). And during the feedback discussion, managers'
      framing of the issues often remains frozen, regardless of the direction the
      conversation takes. Manzoni advises managers not to just settle on the first
      acceptable explanation for a behavior or situation they've witnessed. Bosses also
      need to consider an employee's circumstances rather than just attributing weak
      performance to a person's disposition. In short, delivering more effective
      feedback requires an open-minded approach, one that will convince employees that
      the process is fair and that the boss is ready for an honest conversation.

PMID- 12227145
TI  - Crucibles of leadership.
AB  - What makes a great leader? Why do some people appear to know instinctively how to
      inspire employees--bringing out their confidence, loyalty, and dedication--while
      others flounder again and again? No simple formula can explain how great leaders
      come to be, but Bennis and Thomas believe it has something to do with the ways
      people handle adversity. The authors' recent research suggests that one of the
      most reliable indicators and predictors of true leadership is the ability to
      learn from even the most negative experiences. An extraordinary leader is a kind
      of phoenix rising from the ashes of adversity stronger and more committed than
      ever. In interviewing more than 40 leaders in business and the public sector over
      the past three years, the authors discovered that all of them--young and old
      alike--had endured intense, often traumatic, experiences that transformed them
      and became the source of their distinctive leadership abilities. Bennis and
      Thomas call these shaping experiences "crucibles," after the vessels medieval
      alchemists used in their attempts to turn base metals into gold. For the
      interviewees, their crucibles were the points at which they were forced to
      question who they were and what was important to them. These experiences made
      them stronger and more confident and changed their sense of purpose in some
      fundamental way. Through a variety of examples, the authors explore the idea of
      the crucible in detail. They also reveal that great leaders possess four
      essential skills, the most critical of which is "adaptive capacity"--an almost
      magical ability to transcend adversity and emerge stronger than before.

PMID- 12227146
TI  - Serving the world's poor, profitably.
AB  - By stimulating commerce and development at the bottom of the economic pyramid,
      multi-nationals could radically improve the lives of billions of people and help
      create a more stable, less dangerous world. Achieving this goal does not require
      MNCs to spearhead global social-development initiatives for charitable purposes.
      They need only act in their own self-interest. How? The authors lay out the
      business case for entering the world's poorest markets. Fully 65% of the world's
      population earns less than $2,000 per year--that's 4 billion people. But despite
      the vastness of this market, it remains largely untapped. The reluctance to
      invest is easy to understand, but it is, by and large, based on outdated
      assumptions of the developing world. While individual incomes may be low, the
      aggregate buying power of poor communities is actually quite large, representing
      a substantial market in many countries for what some might consider luxury goods
      like satellite television and phone services. Prices, and margins, are often much
      higher in poor neighborhoods than in their middle-class counterparts. And new
      technologies are already steadily reducing the effects of corruption, illiteracy,
      inadequate infrastructure, and other such barriers. Because these markets are in
      the earliest stages of economic development, revenue growth for multi-nationals
      entering them can be extremely rapid. MNCs can also lower costs, not only through
      low-cost labor but by transferring operating efficiencies and innovations
      developed to serve their existing operations. Certainly, succeeding in such
      markets requires MNCs to think creatively. The biggest change, though, has to
      come from executives: Unless business leaders confront their own preconceptions-
      particularly about the value of high-volume, low-margin businesses--companies are
      unlikely to master the challenges or reap the rewards of these developing
      markets.

PMID- 12227147
TI  - The curse of the superstar CEO.
AB  - When struggling companies look for a new chief executive today, the one quality
      they prize above all others is charisma. But once they've recruited a larger-than
      life leader, they often find that their troubles only get worse. Indeed, as the
      author's new research painfully reveals, the widespread belief in the powers of
      charismatic CEOs can be problematic. Why? First, Khurana says, there's no
      conclusive evidence that charismatic leadership affects an organization's
      performance. And yet--as Kodak's story over the past decade reveals--when a
      company is faltering, boards feel compelled to oust the incumbent chief executive
      and bring in a corporate savior. Second, the insistence on finding a charismatic
      leader, combined with the undefinable nature of charisma, results in selection
      processes that are overly conservative and even irrational. Boards end up
      considering only candidates who have already achieved the rank of CEO or
      president at a high-performing, high-profile company, even if they are not right
      for the job. Third, charismatic leaders deliberately destabilize organizations.
      This can result in a more vibrant company, as it did at General Electric during
      Jack Welch's tenure, but it can also leave a troubled legacy for the organization
      to overcome, as GE, Ford, and Enron have all found. Faith in a company, a
      product, or an idea can unleash tremendous innovation and productivity. But the
      extravagant hopes invested in charismatic CEOs resemble not mature faith but a
      belief in magic. If we are willing to reconsider our notion of leadership, this
      age of faith can be followed by an era of faith and reason.

PMID- 12227148
TI  - Three questions you need to ask about your brand.
AB  - Traditionally, the people responsible for positioning brands have concentrated on
      the differences that set each brand apart from the competition. But emphasizing
      differences isn't enough to sustain a brand against competitors. Managers should
      also consider the frame of reference within which the brand works and the
      features the brand shares with other products. Asking three questions about your
      brand can help: HAVE WE ESTABLISHED A FRAME?: A frame of reference--for Coke, it
      might be as narrow as other colas or as broad as all thirst-quenching drinks-
      signals to consumers the goal they can expect to achieve by using a brand. Brand
      managers need to pay close attention to this issue, in some cases expanding their
      focus in order to preempt the competition. ARE WE LEVERAGING OUR POINTS OF
      PARITY?: Certain points of parity must be met if consumers are to perceive your
      product as a legitimate player within its frame of reference. For instance,
      consumers might not consider a bank truly a bank unless it offers checking and
      savings plans. ARE THE POINTS OF DIFFERENCE COMPELLING?: A distinguishing
      characteristic that consumers find both relevant and believable can become a
      strong, favorable, unique brand association, capable of distinguishing the brand
      from others in the same frame of reference. Frames of reference, points of
      parity, and points of difference are moving targets. Maytag isn't the only
      dependable brand of appliance, Tide isn't the only detergent with whitening
      power, and BMWs aren't the only cars on the road with superior handling. The key
      questions you need to ask about your brand may not change, but their context
      certainly will. The saviest brand positioners are also the most vigilant.

PMID- 12227149
TI  - Pricing and the psychology of consumption.
AB  - Most executives know how pricing influences the demand for a product, but few of
      them realize how it affects the consumption of a product. In fact, most companies
      don't even believe they can have an effect on whether customers use products they
      have already paid for. In this article, the authors argue that the relationship
      between pricing and consumption lies at the core of customer strategy. The extent
      to which a customer uses a product during a certain time period often determines
      whether he or she will buy the product again. So pricing tactics that encourage
      people to use the products they've paid for help companies build long-term
      relationships with customers. The link between pricing and consumption is clear:
      People are more likely to consume a product when they are aware of its cost. But
      for many executives, the idea that they should draw consumers' attention to the
      price that was paid for a product or service is counterintuitive. Companies have
      long sought to mask the costs of their goods and services in order to boost
      sales. And rightly so--if a company fails to make the initial sale, it won't have
      to worry about consumption. So to promote sales, health club managers encourage
      members to get the payment out of the way early; HMOs encourage automatic payroll
      deductions; and cruise lines bundle small, specific costs into a single, all
      inclusive fee. The problem is, by masking how much a buyer has spent on a given
      product, these pricing tactics decrease the likelihood that the buyer will
      actually use it. This article offers some new approaches to pricing--how and when
      to charge for goods and services--that may boost consumption.

PMID- 12227150
TI  - Laser assisted myringotomy for otitis media with effusion in children.
AB  - Otitis media with effusion (OME) is a common childhood illness/disease and a
      major health care priority in the United States. This article describes a
      minimally invasive, office-based procedure, effectively used to treat OME.

PMID- 12227151
TI  - Highlights from the hill: Medicare--insuring health care for the elderly.

PMID- 12227153
TI  - Practice management: understanding when to obtain a waiver for payment.

PMID- 12227155
TI  - Presidential perspectives: where have all the nurses gone?

PMID- 12227156
TI  - [Picornaviruses].

PMID- 12227157
TI  - [HTLV-1: multistep leukemogenesis of adult T-cell leukemia].

PMID- 12227158
TI  - [Topics on herpes simplex virus pathogenesis--roles of viral 'non-essential'
      genes and host immune status].

PMID- 12227159
TI  - [Common features of human beta-herpesviruses].

PMID- 12227160
TI  - [Epstein-Barr virus (1)--Establishment of the infection and dynamics of virus-
      specific T cell responses].

PMID- 12227161
TI  - [Epstein-barr virus gene expression in latent infection and B-lymphocyte growth
      transformation].

PMID- 12227162
TI  - [Cytomegalovirus: strategy for conquering host cells].

PMID- 12227163
TI  - [Reovirus diversity of rotavirus and protection against rotavirus infection].

PMID- 12227164
TI  - [Papovavirus: short- and long-term evolution of human polyomavirus JC virus].

PMID- 12227165
TI  - [Development in the analysis of the pathogenesis of dengue hemorrhagic fever, and
      current status of dengue vaccine].

PMID- 12227166
TI  - [Anti-viral immune responses against hepatitis C virus].

PMID- 12227167
TI  - [Hepatitis virus--the approach to clarification of the mechanisms of virus
      proliferation and the development of its control means].

PMID- 12227168
TI  - [Prion].

PMID- 12227169
TI  - [Measles virus entry as examined by a recombinant virus expressing green
      fluorescent protein].

PMID- 12227170
TI  - [Functional aspects of HIV-1 integrase: from uncoating to integration of viral
      genome].

PMID- 12227171
TI  - [Infection mechanisms of hepatitis C virus].

PMID- 12227172
TI  - [Molecular mechanism of Epstein-barr virus DNA replication].

PMID- 12227173
TI  - [The packaging of influenza viral genome].

PMID- 12227174
TI  - [Functional analyses of regulatory proteins of herpesviruses].

PMID- 12227175
TI  - [Rhabdovirus--the possibility of rabies reemergence in rabies free Japan].

PMID- 12227176
TI  - [The impact of B95a cells on measles virus research].

PMID- 12227177
TI  - [Paramyxovirus (2)--Molecular view of offensive and defensive activities between
      viruses and their hosts].

PMID- 12227178
TI  - [Borna disease virus: its broad host range and neuropathogenesis].

PMID- 12227179
TI  - [A revolutionary change in the diagnosis and treatment of influenza].

PMID- 12227180
TI  - [Research for the infection and replication of influenza virus].

PMID- 12227181
TI  - [Bunyavirus--virus and host relationship: the coevolution between hantavirus and
      rodent].

PMID- 12227182
TI  - [Regulation of retroviral replication and pathogenesis by host factors].

PMID- 12227183
TI  - [Calicivirus].

PMID- 12227184
TI  - [Immune control of HIV-infection and replication].

PMID- 12227185
TI  - [History of HIV diagnostic technology and treatment].

PMID- 12227186
TI  - [Regulatory mechanisms of virus infectivity by HIV accessory genes].

PMID- 12227187
TI  - [Structure and function of HIV virion].

PMID- 12227188
TI  - New 3-[4-(3-substituted phenyl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propanol
      derivatives with dual action at 5-HT1A serotonin receptors and serotonin
      transporter as a new class of antidepressants.
AB  - In this paper a series of new 3-[4-(3-substituted phenyl)piperazin-1-yl]-1
      (benzo[b]thiophen-3-yl)propanol derivatives is presented as a new class of
      antidepressant drugs with dual activity at 5-HT1A serotonin receptors and
      serotonin transporter. The 5-HT1A receptor and 5-HT transporter binding
      affinities of hydroxylic compounds 4 a-e have been determined. The new compounds
      present nanomolar affinity for both activities, and 1-(benzo[b]thiophen-3-yl)-3
      [4-(3-methoxyphenyl)piperazin-1-yl]propan-1-ol (4d) shows values (nM) of Ki = 86
      for 5-HT1A receptors and Ki = 76 for the serotonin transporter, respectively.

PMID- 12227189
TI  - Synthesis of some 3- and 4-substituted 1,5-diphenylpyrrolidine-2,4-diones as
      potential antimicrobial and antineoplastic agents. Reactions with tetramic acid,
      Part 5.
AB  - The condensation of 1,5-diphenylpyrrolidine-2,4-dione (1) with the carboxyl
      compounds 2a-f afforded the corresponding 3-arylidene-1,5-diphenylpyrrolidine-2,4
      diones 3a-f. Reaction of the parent compound 1 with isatin (4) yielded the
      condensation product 5 in an acidic medium, whereas compound 6 was obtained in an
      alkaline medium. The condensation of the primary amines 7a-f with compound 1
      afforded the corresponding 4-substituted amino-1,5-diphenyl-delta 3-pyrrolin-2
      ones 8a-f. All the compounds synthesized were screened for their antimicrobial
      activity, and four compounds were selected for screening for their antineoplastic
      activity. The compounds tested showed both antimicrobial and antineoplastic
      activities.

PMID- 12227190
TI  - [Synthesis, structure and stability of 4-aryl-4H-pyran-3,5-dicarboxylic acid
      esters].
AB  - Eight new 4-aryl-2,6-dimethyl-4H-pyrane-3,5-dicarboxylic acid esters 2 and a new
      2-amino-2-nor derivative 7 are synthesized using known methods, whose limitations
      are shown. In contrast to the isoelectronic 4-aryl-1,4-dihydro-pyridines (DHP) 1
      the compounds 2e, g possess a nearly planar heterocycle, as found by X-ray
      crystal structure analysis. The 4H-pyrane-3,5-dicarboxylic acid ester 2e with m
      substitution exhibits s-cis/s-cis-conformation, while compound 2g with o
      substitution of the aromatic ring represents s-cis/s-trans-conformation. The half
      wave potentials (E1/2) show that 4H-pyranes are more stable than the DHP 1. The
      substitution of the 4-phenyl ring with an electron donating group decreases the
      potential considerably, whereas an electron acceptor group slightly increases the
      potential. Replacement of the 2-methyl group by the amino function causes a
      dramatic loss of stability.

PMID- 12227191
TI  - [Reactions between dialkylamine drugs, 2,3-dichloro-1,4-naphthoquinone and
      acetaldehyde].
AB  - Dialkylamine drugs desipramine, propanolol, pindolol, alprenolol and metoprolol
      4a-e react with 2,3-dichloro-1,4-naphthoquinone (2) and acetaldehyde to give red
      coloured 2-dialkylamino-3-chloro-1,4-naphthoquinones 5a, b, d, e, blue coloured 2
      dialkylamino-vinyl-3-chloro-1,4-naphtho-quinones 1a-e and bluish green coloured 2
      dialkylamino-butadienyl-3-chloro-1,4-naphthoquinones 6b-e. The colour products
      are isolated by column chromatography.

PMID- 12227192
TI  - Validated HPLC method for the determination of tinidazole in human serum and its
      application in a clinical pharmacokinetic study.
AB  - A high performance liquid chromatographic (HPLC) method for the determination of
      tinidazole in human serum using metronidazole as internal standard (IS) is
      described. Protein precipitation is used for the preparation of sample. Mobile
      phase consisting of 0.002 M phosphate buffer, methanol and acetonitrile mixture
      (85:7.5:7.5/v/v/v) was used at a flow rate of 1 ml/min on a C18 column. The
      eluate was monitored using an UV/Vis detector set at 320 nm. Ratio of peak area
      of analyte to IS was used for quantification of serum samples. The absolute
      recovery was greater than 95% over a concentration range of 0.5 to 30
      micrograms/ml and the limit of quantitation was 0.05 microgram/ml. The intra-day
      relative standard deviation (RSD) measured at 0.5, 5, 15 and 30 micrograms/ml
      ranged from 0.36 to 6.14%. The inter-day RSD ranged from 1.14 to 4.21%. The
      method is simple, sensitive and has been successfully used in a pharmacokinetic
      study conducted in healthy human volunteers.

PMID- 12227194
TI  - Solubility of hypericin in methanol and methanol-pyridine.
AB  - The solubility of hypericin in methanol and methanol-pyridine (99:1, v/v) was
      determined. The addition of pyridine turned out to enhance the solubility of
      hypericin. In pure methanol only 37.17 micrograms/ml could be dissolved. In
      comparison, 320.91 micrograms hypericin were soluble in one ml methanol-pyridine
      (99:1, v/v).

PMID- 12227193
TI  - Determination of iodine values using 1,3-dibromo-5,5-dimethylhydantoin (DBH)
      without the employment of chlorinated hydrocarbons. Analytical methods of
      pharmacopoeias with DBH in respect to environmental and economical concern. Part
      17.
AB  - Low and medium iodine values of fixed oils and fats can be determined in glacial
      acetic acid within reduced waiting times of only 5 min. Highly unsaturated
      compounds such as those of linseed oil, cod-liver oil, sunflower oil, soybean
      oil, wheat germ oil and the emulsifier sorbitan trioleate result too low values
      in comparison to PH. EUR. 2002 [2] and USP 2000 [3]. Cocoa butter with a low
      iodine number is insoluble in glacial acetic acid. The iodine values of
      nonionogenic emulsifiers such as ceteareth-30 (Macrogol cetostearyl ether PH.
      EUR. 2002), oleth-10 resp. 20 (Macrogol oleyl ether PH. EUR. 2002) and
      polysorbate-80 PH. EUR. 2002 are obtained in aqueous solutions. Oleth-2 (Macrogol
      oleyl ether PH. EUR. 2002), polyoxyl-40 castor oil (Macrolglycerol ricinoleate
      PH. EUR. 2002), polysorbate-60 PH. EUR. 2002 and sorbitan trioleate PH. EUR. 2002
      need the addition of ethyl acetate. Fixed oils even with high iodine values can
      be determined in an o/w emulsion with a reaction time of 5 min in most cases,
      when nonionogenic emulsifiers such as ceteareth-30, polyoxyl-30 glycerol
      monolaurate or polyoxyl-60 hydrogenated castor oil (Macrolglycerol
      hydroxystearate PH. EUR. 2002) are used.

PMID- 12227195
TI  - In vitro deposition of the respirable fraction of dry powder inhalations
      determined by laser diffractometry and inertial impaction.
AB  - Particle size analysis of drug and excipient is of particular interest for dry
      powder inhalation (DPI) formulations development and quality control. In this
      work, the deposition in the upper, the medium and the lower (i.e. the respirable
      fraction) Twin Impinger compartments of sodium cromoglycate (SCG), lactose (as
      excipient) and a 1:1 mixture thereof was determined by chemical analysis using a
      DPI device--the Micro-hale--and compared with the results obtained by laser
      diffractometry for the same fractions. The analytical method for the SCG
      determination consisted of ultraviolet spectrophotometry and, for the lactose,
      high performance liquid chromatography with refractive index detection was used.
      Laser diffractometry as a quickly operating routine method can substitute the
      chemical analysis in order to evaluate the respirable fraction, under the
      conditions of the present work and therefore making formulation development
      easier and quicker.

PMID- 12227197
TI  - Induction of neutral endopeptidase and angiotensin-converting enzyme activity of
      SK-N-SH cells in vitro by quercetin and resveratrol.
AB  - Quercetin and resveratrol are weak inhibitors of neutral endopeptidase (NEP) and
      angiotensin-converting enzyme (ACE) activity of the neuroblastoma cell line SK-N
      SH. The long term incubation of the cells for 4 days with quercetin, resveratrol
      and a combination of both substances in concentrations lower than necessary for
      inhibition of NEP and ACE activity induced the cellular enzyme activity of NEP
      and ACE associated with an inhibition of cellular proliferation. The long term
      treatment of neuroblastoma cells with quercetin and resveratrol enhanced the
      differentiation state of the cells. Taking into account the significance of NEP
      and ACE for the degradation of amyloid beta peptides, the effect of quercetin and
      resveratrol as constituents of red wine for a neuroprotective activity is
      discussed.

PMID- 12227196
TI  - Oligoethylene ester derivatives of ketoprofen, naproxen and diclofenac as oral
      prodrugs: a pharmacological evaluation.
AB  - Polyoxyethylene esters of ketoprofen (1a-e), naproxen (2a-e) and diclofenac (3a
      e) were tested in vitro to determine their stability in pH 7.4 phosphate buffer
      and in simulated gastric fluid (pH 2.0 buffer) and their susceptibility in
      undergoing enzymatic cleavage in human plasma. Furthermore their in vivo
      antiinflammatory and analgesic activity and GI toxicity were evaluated in
      rodents. All the prodrugs showed a good stability both in pH 7.4 phosphate buffer
      and in pH 2.0 buffer. They were readily hydrolyzed by human plasma and, for each
      group of prodrugs, no significant difference in hydrolysis rate was observed as
      the length of the oligoethylene chain increased. Esters 1a-e, 2a-e and 3a-e
      showed an anti-inflammatory activity (expressed as inhibition percent of
      carrageenan-induced edema in the rat) similar to that of their respective parent
      drug although at higher doses. The results obtained in the writhing test in mice
      demonstrated that all the prodrugs tested exhibited, following acute
      administration, a good analgesic effect. Furthermore these esters were
      significantly less irritating to the gastric mucosa, although administered at
      doses higher than the respective parent drug.

PMID- 12227198
TI  - Sedative, anticonvulsant and behaviour modifying effects of Centranthus
      longiflorus ssp. longiflorus: a study of comparison to diazepam.
AB  - The aqueous extract of Centranthus longiflorus ssp. longiflorus (CLE) was
      investigated for sedative, anticonvulsant and behaviour modifying activity using
      thiopental sleeping, caffeine induced convulsion and forced swimming depression
      tests. When the effects of the aqueous extract of CLE (100 mg/kg) was compared to
      diazepam, it showed similar sedative and anticonvulsant effects to those produced
      by diazepam (5 mg/kg).

PMID- 12227199
TI  - New steroidal saponins from Agave lophantha Schiede and their pharmacological
      evaluation.
AB  - The structures of one new monodesmosidic spirostanoside and one new bisdesmosidic
      furanostanol glycoside isolated from leaves of Agave lophantha Schiede have been
      determined by means of spectroscopic and chemical methods as (25R)-5 beta
      spirostan-3 beta-ol-3-O-(beta-D-apiofuranosyl(1-->4)beta-D -glucopyranosyl(1-
      >3)[beta-D-glucopyranosyl(1-->2)]beta-D -galactopyranoside) and 26-O-beta-D
      glucopyranosyl(25R)-5 beta-furost-20(22)-ene-3 beta, 26-diol-3-O-(beta-D
      xylopyranosyl(1-->3)-[beta-D-glucopyranosyl(1--2)] beta-D-galactopyranoside),
      respectively. The 1H and 13C NMR resonances of the two compounds were assigned by
      NMR (1H, 13C, HOHAHA, 1H-1H COSY, HMQC, HMBC, NOE difference) studies. The
      pharmacological activities of the saponin containing fraction are discussed.

PMID- 12227201
TI  - Bioactive saponins from Dioscorea futschauensis.
AB  - A new anti-neoplastic spirostanol saponin, (25S)-spirost-5-en-3 beta, 27-diol-3O
      [alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl (1-->3)]-beta-D
      glucopyranoside and three known compounds viz. prosapogenin A of dioscin, dioscin
      and gracilin were isolated from Dioscorea futschauensis by bioactivity-guided
      fractionation. Their structures were elucidated mainly by means of spectroscopic
      analysis. Their bioactivity against Pyricularia oryzae and cytotoxic activity on
      ts-FT210 cell line was evaluated.

PMID- 12227200
TI  - Terpenoid constituents of Aster subspicatus and A. ageratoides.
AB  - Chemical investigation of the aerial parts of Aster subspicatus afforded a new
      sesquiterpene lactone, 8 alpha-acetoxy-1 alpha-hydroxy-3 alpha,4 alpha-epoxy-5
      alpha,7 alpha H-9,11(13)-guaiadien-12,6 alpha-olide (1), in addition to the known
      compounds arteglasin-B (2), diversoside (3), and 2-phenylethyl beta-D
      glucopyranoside. Re-investigation of Aster ageratoides afforded the known
      compounds crotocorylifuran, and oplopanone. The structure of the new compound was
      determined by spectroscopic methods particularly high resolution 1H, 13C NMR,
      DEPT, 2D 1H-1H and 1H-13C COSY NMR and HMBC analysis.

PMID- 12227202
TI  - Lunamarin C, a new terpenoid coumarin from Clausena heptaphylla.
AB  - The petroleum ether extract of the leaves of Clausena heptaphylla afforded a new
      coumarin, lunamarin C (1). Its structure was determined by extensive analysis of
      spectral data, including 2D NMR and by comparison with structurally related
      compounds, lunamarins A (2) and B (3).

PMID- 12227203
TI  - [Professor Dr. phil. Hans Wojahn (1902-1965)].
AB  - The pharmacist Hans Wojahn obtained his PhD under the supervision of Karl W.
      Rosenmund from the university of Kiel. There he also received his habilitation
      for pharmaceutical chemistry. From 1942-1945 he was lecturer and associate
      professor at the institute of pharmacy and food chemistry of the university of
      Jena. After functions in the pharmaceutical industry and the research institute
      of tuberculosis in Borstel he assumed the direction of the pharmaceutical
      laboratories of the Max-von-Pettenkofer institute in Berlin. He has been
      appointed honorary professor at the Free University of Berlin. Professor Wojahn
      influenced decisive the edition of the 3. addendum of the DAB 6 and has been
      regarded father of the DAB 7 of the Federal Republic of Germany. With regard to
      the pharmacopoeia the bromometric assay of drugs and especially those of
      sulfonamides is placed in the foreground of his scientific work. A complete
      chronological arranged list of publications has been established.

PMID- 12227205
TI  - Pulse polarographic determination of levofloxacin in tablets.

PMID- 12227204
TI  - Synthesis of d-tryptanthrin.

PMID- 12227206
TI  - Separation of racemic drugs on chiral resorcinarene-bonded HPLC-columns.

PMID- 12227207
TI  - Managing during times of uncertainty. Part II--Long-term strategies.
AB  - It could be argued that uncertainty is currently part and parcel of most
      businesses. The degree of uncertainty may vary at times, but many occupational
      health nurse managers learn to live with a degree of insecurity in their jobs,
      and with the service they manage. The strategies discussed in this column can
      help occupational health nurses manage their departments more efficiently under
      the best of circumstances, and help identify strategies to use in times of
      increased uncertainty.

PMID- 12227208
TI  - Cardiovascular health--a workplace priority.

PMID- 12227209
TI  - Stroke. Risks, recognition, and return to work.
AB  - 1. The two major classifications of stroke are ischemic and hemorrhagic. Ischemic
      strokes account for 75% of all strokes and result from the complete occlusion of
      an artery. Hemorrhagic strokes, often caused by aneurysm or hypertension, are
      caused by the rupture of a cerebral blood vessel and bleeding into the
      surrounding tissue. 2. The signs and symptoms of stroke may include unilateral
      weakness or paralysis, a sagging of one side of the face, double or blurred
      vision, vertigo, numbness or tingling, and language disturbances. 3. Management
      of ischemic stroke may include thrombolytic agents (e.g., heparin, warfarin) if
      the individual is treated within 6 hours after the onset of symptoms. Diagnostic
      tests may include, computed tomography scan, transesophageal echocardiagraphy,
      Doppler ultrasonography, and electrocordiography. 4. Occupational health nurses
      can be actively involved in helping workers modify their risks for stroke,
      developing and implementing an action plan if an individual is experiencing a
      stroke, and facilitating the individual's reentry into the worksite after
      rehabilitation is completed.

PMID- 12227210
TI  - Update on managing hypercholesterolemia. The new NCEP guidelines.
AB  - 1. The Third Report of the National Cholesterol Education Program Expert Panel on
      Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATPIII)
      will significantly increase the number of Americans treated for
      hypercholesterolemia. 2. The ATPIII focuses on lowering low density lipoprotein
      cholesterol as a primary initiative and using exercise, diet, and pharmacotherapy
      as a means for lowering coronary heart disease and risks. 3. The new guidelines
      list low density lipoprotein cholesterol levels of less than 100 mg/dL as optimal
      for all clients. 4. The ATPIII places increased attention on high triglyceride
      levels (> 200 mg/dL) and on early detection and appropriate aggressive treatment
      for clients at risk for coronary heart disease and events.

PMID- 12227211
TI  - The Lucent-Takes-Heart cardiovascular health management program. Successful
      workplace screening.
AB  - This prospective, pre- and post-evaluation of a worksite cardiovascular health
      management program consisted of employee education, measurement of cardiovascular
      risk factors, and onsite individual counseling for all employees, along with
      follow up screening for high risk participants. Of 1,099 employees (16.4% of
      those eligible) who participated in the initial screening, 596 (54.2%) were
      classified as high risk. A total of 167 (28.0%) high risk participants completed
      the 6 month follow up screening. Most high risk participants in the 6 month
      follow up screening reported they had increased their exercise (64.7%), improved
      their diet (71.3%), and visited a physician (61.7%). A minority of the
      participants (16.8%) began new cardiovascular medications, and 2.4% were
      diagnosed with diabetes. In addition, there were statistically significant
      decreases in the percentages of participants with elevated systolic blood
      pressure, diastolic blood pressure, low density lipoprotein cholesterol, and
      total cholesterol to high density lipoprotein ratio. Almost all (99.7%) of the
      909 participants (82.7% of all participants) who completed the satisfaction
      survey were satisfied or very satisfied with the overall program. Screening in
      the workplace can identify individuals at high risk for cardiovascular disease.
      In this study, more than half of the participants were classified as high risk.
      Most high risk individuals who attended the 6 month follow up screening had
      improved their cardiovascular health, but attrition remains a challenge for
      worksite programs.

PMID- 12227212
TI  - Tularemia. A pathogen in nature and a biological weapon.
AB  - Tularemia as a potential biological weapon is of great concern because F.
      tularensis is a hardy organism that can be spread with a small inoculum. In
      addition, tularemia can be contracted through nature, predominately in rural
      areas. This disease can be spread by a wide variety of animals and can range from
      skin lesions to multi-organ involvement. The severity varies with amount of
      inocula, the virulence of the bacterium, and the port of entry. Exposure to
      aerosolized forms of F. tularensis, the major concern with bioterroism, can
      rapidly lead to respiratory failure and death. Untreated, other forms of
      tularemia can spread through the blood stream to other organs, leading to sepsis
      and death. Early recognition and treatment is tantamount to treatment and
      prevention of morbidity and mortality. Occupational health nurses are on the
      front line and must be assertive in identifying risk factors associated with
      exposure. Furthermore, education of the general population about exposure through
      nature can potentially decrease the incidence of tularemia. Occupational health
      nurses, as one of the largest health specialties in the workplace, may be the
      first contact for the exposed individual. Tularemia is treatable with knowledge
      of prevention, astute assessment, prompt identification, and treatment. Combined,
      they are powerful nursing tools in achieving optimal outcomes.

PMID- 12227213
TI  - Inspection tips.

PMID- 12227214
TI  - Update on the management of chronic hepatitis B.
AB  - Chronic hepatitis B virus infection is common and may cause significant disease
      morbidity, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
      Hepatitis B surface antigen-positive patients should have a detailed serologic
      evaluation including determination of the level of replication. Patients with
      high levels of virus replication and those with co-infection should be considered
      for treatment. Interferon was the first approved therapy for chronic hepatitis B
      and remains one of the most effective options. Newer agents, such as lamivudine
      and adefovir dipivoxil, offer excellent antiviral activity and ease of
      administration, although drug resistance is common with lamivudine.

PMID- 12227215
TI  - Valdecoxib.
AB  - Valdecoxib is a selective COX-2 inhibitor that is similar in anti-inflammatory
      activity to the other selective COX-2 inhibitors (e.g., celecoxib and rofecoxib).
      Valdecoxib is at least equally as effective as ibuprofen, naproxen, and
      diclofenac in the treatment of osteoarthritis and rheumatoid arthritis, but is
      safer in terms of gastrointestinal toxicity. Valdecoxib is also indicated for
      treatment of dysmenorrhea and useful in other pain conditions. There have been no
      head-to-head comparisons of valdecoxib and celecoxib or rofecoxib in the
      treatment of osteoarthritis, rheumatoid arthritis, or various pain conditions.

PMID- 12227216
TI  - Best of DDW 2002. Highlights from the 2002 Digestive Disease Week. May 19-22,
      2002, San Francisco, CA.

PMID- 12227217
TI  - Considering virtual colonoscopy.
AB  - Virtual colonoscopy continues to show promise as a colorectal cancer screening
      test and is technically evolving rapidly. It has particular advantages with
      regard to acceptability by both radiologists and patients. Important steps to
      achieve implementation include clear delineation of all of the technical
      components necessary to produce consistent high performance and development of
      clear-cut recommendations for interpretation and management of polyps of various
      sizes and the range of extracolonic findings identified. Development of an
      effective methodology to perform the test without bowel preparation or
      demonstration of cost-effectiveness for identification and treatment of one or
      more significant extracolonic diseases would be major breakthroughs, provided
      they are still accompanied by effective detection of significant colon neoplasms.
      Issues regarding general effectiveness and cost-effectiveness must be resolved
      before virtual colonoscopy is endorsed for widespread colorectal cancer screening
      or utilized for that purpose.

PMID- 12227218
TI  - [Attention deficit hyperkinetic syndrome (ADHS) and stimulants].

PMID- 12227220
TI  - [Selective serotonin reuptake inhibitors and newer antidepressive substances in
      child and adolescent psychiatry].
AB  - OBJECTIVES: Since the first report on a selective serotonin reuptake inhibitor
      (SSRI) in 1974, not only have new substances in the group of the SSRI been
      developed, but also completely new groups of antidepressants. Among these newer
      groups, characterised by their pharmacological properties, are the serotonin2
      antagonists/serotonin reuptake inhibitors (SARI), the noradrenergic and specific
      serotonergic antidepressants (NaSSA), the noradrenaline and dopamine reuptake
      inhibitors (NDRI) and the serotonin and noradrenaline reuptake inhibitors (SNRI).
      This review describes the properties and side effects of the newer
      antidepressants and compares them to those of the older substance groups like
      tricyclic antidepressants (TCA), MAO inhibitors (MAOI) and SSRI. Studies of
      antidepressants in children and adolescents with depression are presented and
      compared for differences between the older and newer substances. METHODS: A
      Medline search was performed up to and including January 2002. RESULTS: Three
      double-blind, placebo-controlled studies of SSRI and one double-blind, placebo
      controlled study of the newer antidepressant venlafaxine in children and
      adolescents with depression have been conducted. However, there is a great number
      of prospective and retrospective studies. Furthermore, seven double-blind,
      placebo-controlled studies of SSRI, as well as several prospective and
      retrospective of the newer antidepressants have been carried out in children and
      adolescents with other psychiatric disorders. CONCLUSIONS: The studies of the
      SSRI and the newer antidepressants conducted to date are promising. Nonetheless,
      further double-blind, placebo-controlled studies are necessary.

PMID- 12227219
TI  - [Thrombocytic serotonin concentration in depressed children and adolescents].
AB  - OBJECTIVES: This study pursued the question to what extent a correlation exists
      between the platelet serotonin concentration and depressive and/or suicidal
      behaviour in children and adolescents. METHODS: Within a 16-month period, the
      platelet serotonin concentration was determined in all admitted inpatients (n =
      145, age: 4 to 19 years) by means of fluorescent spectroscopy according to a
      standardised protocol. The severity of depressive symptoms was assessed by
      administration of the DIKJ to a subset of patients. The different diagnostic
      groups were formed according to the criteria of the ICD-10. RESULTS: A decrease
      in the platelet serotonin concentration was found with increasing age. While
      platelet serotonin concentrations were higher in male patients than in females,
      the girls showed higher depression scores on the DIKJ. A negative correlation
      existed between the platelet serotonin concentration and the degree of depression
      measured on the DIKJ in all diagnostic groups. Independent of the clinical
      diagnosis significantly lower concentrations of platelet serotonin were found in
      children and adolescents who had attempted suicide immediately before admission
      to hospital. The same is true for the group of depressive disorders, with a
      subgroup of patients who had attempted suicide shortly before also showing
      significantly lower concentrations of platelet serotonin. CONCLUSIONS: The
      present investigation supports the contention that depression in childhood and
      adolescence is related to a lack of serotonin in platelets, respectively,
      analogous to the platelet model, to a lack of serotonin in central structures,
      and that a relative serotonin deficiency could thus be an indicator of suicidal
      ideation.

PMID- 12227221
TI  - [Sleep disorders and child and adolescent psychiatric illnesses].
AB  - As a symptom of many psychiatric disorders of childhood and adolescence, sleep
      disturbances often complicate the course and treatment of the underlying
      disorder. A somatic aetiology, e.g., as in Kleine-Levin syndrome or narcolepsy,
      may lead to diagnostic misinterpretations. It is not clear whether specific
      alterations of sleep architecture already exist in this age group and are thus
      trait markers for psychiatric disorders. Although it is well-known that sleep
      problems in adults, especially insomnia, are important in the later development
      of depressive syndromes, it is not clear whether persistent sleep problems during
      childhood constitute markers of vulnerability for psychiatric disorders. This
      review demonstrates interactions between sleep disturbances and psychiatric
      disorders of childhood and adolescence and their importance for assessment and
      therapy.

PMID- 12227222
TI  - [Psychogenic paralysis in childhood and adolescence].
AB  - OBJECTIVES: This article presents the characteristics of psychogenic paralysis in
      children and adolescents. The overview covers the changes in its diagnostic
      classification from ICD-6 to ICD-10. METHODS: Characteristics of this diagnostic
      entity are presented and epidemiological data discussed on the basis of clinical
      studies from the literature. Among the dissociative disorders in children and
      adolescents, psychogenic paralysis shows a characteristic distribution according
      to sex and age. Furthermore the literature indicates a better prognosis for
      patients with this symptomatology than for children and adolescents with
      pseudoseizures and psychogenic vision disorders. RESULTS: Iatrogenic invasive
      diagnostic and therapeutic procedures, somatic injuries, infections and a model
      for the symptoms play an important role in the pathogenesis of gait disorders.

PMID- 12227223
TI  - [Early childhood autism: age at onset and early regression].
AB  - OBJECTIVES: The age at onset of autistic symptoms and an early setback in the
      social or language development of children with early infantile autism has been
      discussed in the literature as a possible marker for a special subgroup.
      Information on the number of children with these symptoms varies widely in
      different reports. The purpose of this study is to analyse how often a late onset
      or a regression in social or language behaviour are reported in a clinical sample
      and how they are related to other abnormalities found in these children. METHODS:
      The files on 101 children seen in a specialised outpatient department since 1993
      and diagnosed with early infantile autism were analysed. Information on the six
      axes of the multiaxial classification, the age at onset of symptoms and at
      setback in social or language development was extracted. RESULTS: Of these 101
      children, 75% were described as being different from other children from the
      beginning. Fourteen showed a regression in social behaviour and 21 a regression
      in language development. These symptoms did not correlate with intelligence or
      the status of language development at the time of the assessment. Children with a
      setback more frequently had epileptic seizures than did children without a
      setback. CONCLUSIONS: The accumulated data permit the hypothesis that children
      with a late onset of autistic symptoms or a regression constitute a special
      subgroup within the group of children with early infantile autism. These symptoms
      should lead to an intensive diagnostic process in order to exclude epileptic
      abnormalities.

PMID- 12227224
TI  - LSD-induced Hallucinogen Persisting Perception Disorder with depressive features
      treated with reboxetine: case report.
AB  - We would like to present the case of a patient who had a prior history of
      cannabis, ecstasy (MDMA) and LSD abuse and who developed both Hallucinogen
      Persisting Perception Disorder (HPPD) and a major depressive episode. Following
      two unsuccessful SSRIs trials, reboxetine was prescribed. During a six-month
      follow-up period on reboxetine 6 mg./day, no exacerbation of the visual
      disturbance or recurrence of the depressive features were reported. Reboxetine
      may have an alpha 2 adrenoreceptor modulating effect on both noradrenaline and
      serotonin release, thus reboxetine's alpha 2 adrenoreceptor modulating effect on
      noradrenaline release may affect sympathetic activity and be involved in the
      recovery process.

PMID- 12227225
TI  - Benzodiazepine abuse in a methadone maintenance treatment clinic in Israel:
      characteristics and a pharmacotherapeutic approach.
AB  - OBJECTIVE: 1) To study the prevalence, course and correlates of benzodiazepine
      (BZD) abuse in an Israeli methadone maintenance treatment (MMT) clinic; and 2) to
      present preliminary results of an open clinical study on the treatment of BZD
      addiction in MMT patients using BZD maintenance. METHODS: Study 1 was carried out
      on 196 patients who were in MMT for at least one year. Objective information on
      drug use (urine testing) was recorded, and the one-year retention rate was
      measured. Demographic data and history of abuse were obtained, and a self-rated
      psychopathology and psychological distress questionnaire was administered. The
      second study was an open one. Twenty BZD-addicted patients were given clonazepam
      maintenance treatment (CMT) and were started on a daily regimen of 6 mg. followed
      by a gradual tapering until an individual dose was reached. This maintenance dose
      was the lowest level at which the patient still expressed satisfaction with the
      BZD dose without reporting craving or overdose. Failure was defined by three
      daily consecutive BZD uses above the permitted dose. RESULTS: BZD abuse was
      significantly reduced during the first year of MMT (from 55 to 43%, P < .000),
      although a number of patients started to abuse BZDs during this period. BZD
      abusers (BAs) were found more often to be polydrug abusers, their methadone
      dosage was higher than non-abusers (NBAs), they started to abuse drugs in general
      and heroin in particular earlier than NBA, and they had higher self-rated
      psychopathology and psychological distress scores. The second study showed that
      CMT was successful in 75% of the patients over a period of six months and that it
      is, therefore, a promising mode of treatment for BZD-dependent MMT patients.
      CONCLUSIONS: MMT patients who abuse BZDs are at an increased risk for continuing
      polydrug abuse. Although our results are to be taken cautiously due to the
      inherent limitation of a non-controlled non-randomized pilot study, ongoing
      maintenance with clonazepam seems to be well tolerated and a stabilizing and
      satisfying pharmacotherapy for BZD dependent MMT patients.

PMID- 12227226
TI  - Heroin detoxification with a single high dose of buprenorphine.
AB  - Twenty street-heroin dependent subjects were given 32 mg of sublingual
      buprenorphine, following heroin abstinence of 24 hours. Withdrawal symptoms were
      monitored during the first few hours, and followed for six days after
      buprenorphine administration, after which naltrexone 50 mg was introduced to
      prevent future heroin use. All 20 subjects completed the seven-day trial with
      negligible withdrawal symptoms, and smooth transition to naltrexone. These
      results strongly demonstrate that symptom-free detoxification from heroin can be
      obtained by a single high dose of buprenorphine.

PMID- 12227227
TI  - The effects of alcohol and illicit drugs on the human embryo and fetus.
AB  - Women at childbearing age often use alcohol and various illicit drugs such as
      cocaine and heroin. These agents pass through the human placenta and may affect
      the developing embryo and fetus. Indeed, large amounts of alcohol ingested by the
      pregnant woman may produce a specific syndrome manifested by prenatal and
      postnatal growth retardation, a variety of facial dysmorphic features and mental
      retardation. Ingestion of smaller amounts of alcohol will produce the fetal
      alcohol effects with only few and minor dysmorphic features but with
      developmental delay and some degree of intellectual impairment. Cocaine use
      during pregnancy may apparently result in an increase in the rate of congenital
      anomalies, of stillbirth and of intrauterine growth retardation. The use of
      heroin and opiates does not seem to increase the rate of major congenital
      anomalies, but it reduces fetal growth and increases the rate of intrauterine
      fetal death. Studies on the developmental outcome of children born to cocaine or
      heroin dependent mothers seem all to show psychomotor developmental delay at a
      young age. At school age these children have intellectual impairment and a very
      high rate of inattention and/or hyperactivity. We should therefore address our
      efforts in improving the environment of these children and in treating the early
      symptoms of inattention and hyperactivity, even before the child reaches school.

PMID- 12227228
TI  - Drug and alcohol-related emergency department visits: results of a pilot survey
      in two hospitals in Israel.
AB  - There is no system for reporting drug and alcohol-related emergency department
      (ED) visits in Israel. This pilot survey was aimed at examining the feasibility
      of establishing an ED surveillance system in a general hospital and a psychiatric
      hospital. We describe the design and preliminary results of a pilot-survey
      conducted in the emergency departments of two hospitals in Northern Israel.
      Active and passive case identification was conducted in Rambam Hospital and Tirat
      Carmel Psychiatric Hospital, from August, 1999-January, 2000. A total of 160 ED
      patients were identified, 64% as drug-related, with heroin being the most common
      drug. The majority of cases were identified through self-reports. Overdose and
      IVDU complications accounted for 20% of drug cases identified at Rambam Hospital,
      and injury and motor vehicle accidents accounted for 12% of all visits at this
      hospital. We did not attempt to estimate the proportion of all ED visits that are
      associated with drugs and/or alcohol. Under-ascertainment of cases and incomplete
      data recording remain major concerns for a survey of this nature. Results of this
      pilot survey indicate that with proper training of ED nurses a national ED
      surveillance system can be successfully and efficiently established in general
      hospitals and psychiatric hospitals in Israel.

PMID- 12227229
TI  - An integration of three approaches to addiction and methadone maintenance
      treatment: the self-medication hypothesis, the disease model and social
      criticism.
AB  - The two models which have most affected theory and practice of addiction medicine
      have been the disease model and the self-medication hypothesis. The disease
      model's fundamental concept is that the addicted individual is sick and suffers
      from a disease. The self-medication hypothesis proposes that drug and alcohol
      users are attempting to cope with an underlying psychological or social disorder
      by means of self-medication. These two viewpoints are presented in the light of a
      number of specific methadone maintenance treatment and drug abuse related issues
      such as the question whether drug abuse is an illness of the body, the mind or
      society; whether the disease model really de-stigmatized drug abuse; what the
      correct methadone dosing policy should be; the place of psychotherapy in
      methadone maintenance treatment and drug abuse and how polydrug abuse should be
      treated. These issues are discussed and an integrated approach is suggested
      stressing the need for social criticism and a renewed social policy towards drug
      abuse in general and its treatment in particular.

PMID- 12227230
TI  - Changes in psychoactive drug use in Israel from 1990 until 2001.

PMID- 12227231
TI  - Science-based views of drug abuse and addiction.

PMID- 12227232
TI  - Challenge paradigms in psychiatric research: what do they contribute and are they
      ethical?

PMID- 12227233
TI  - Commentary: first, do no harm. Then, do some good: ethics and human experimental
      psychopharmacology.

PMID- 12227234
TI  - Flashback and Hallucinogen Persisting Perception Disorder: clinical aspects and
      pharmacological treatment approach.
AB  - One unique characteristic of lysergic acid diethylamide (LSD) and LSD-like
      substances is the recurrence of some of the symptoms which appeared during the
      intoxication after the immediate effect of the hallucinogen has worn off. This
      recurring syndrome, mainly visual, has not been clearly understood, appreciated
      or distinguished from other clinical entities by clinicians. The terms Flashback
      and Hallucinogen Persisting Perception Disorder (HPPD) are used interchangeably
      in the professional literature. Flashback is a usually short-term, non
      distressing, spontaneous, recurrent, reversible and benign condition accompanied
      by a pleasant affect. In contrast, HPPD is a generally long-term, distressing,
      spontaneous, recurrent, pervasive, either slowly reversible or irreversible, non
      benign condition accompanied by an unpleasant dysphoric affect. Flashback and
      HPPD appear to be part of a vast and broad spectrum of non-psychopathological and
      psychopathological states reported by hallucinogen users. Pharmacological agents
      such as clonidine, perphenazine and clonazepan have been shown to ameliorate this
      syndrome in some of the individuals seeking treatment.

PMID- 12227235
TI  - Role of experience and context in learning to diagnose Lyme disease.
AB  - INTRODUCTION: A recent review of research in continuing medical education
      suggests that scholarship should be integrated with practice so that practical
      problems can be addressed with theoretically derived yet applicable solutions.
      This project develops a theory describing how physicians learn and formulate
      decisions in the context of diagnosing Lyme disease in order that educational
      programs can be designed to improve accuracy in diagnosis of this disease.
      METHODS: A qualitative study using grounded theory methodology was performed to
      explore the learning process of physicians when diagnosing Lyme disease. Nine
      physicians were interviewed, and the interview transcripts were coded into
      categories to form a theory about how physicians learn in practice. RESULTS:
      Patient-physician interactions initiate the learning process by setting a context
      for which physicians frame a problem according to familiarity. Repetitive,
      similar, and counter-experiences, combined with cognitive knowledge, contribute
      to that framework and influence how the problem is framed along a continuum of
      familiarity. Furthermore, these experiences serve as information that influences
      diagnostic decisions and physicians' behaviors. DISCUSSION: For teaching and
      learning, cases and examples should include sufficient variety, repetition, and
      counterexperiences that allow a physician to appropriately recognize and
      categorize a patient's signs and symptoms into a disease category. Resources for
      information should be readily available and current. Preceptors and physician
      colleagues should provide timely feedback on diagnostic accuracy, and case
      studies should be presented with contextual elements that facilitate the
      diagnosis of Lyme disease.

PMID- 12227236
TI  - Does patient partnership in continuing medical education (CME) improve the
      outcome in osteoporosis management?
AB  - INTRODUCTION: There is an apparent gap between physicians' knowledge and their
      practical application of such knowledge. Educating patients to educate physicians
      toward improved care has been shown to be effective in selected settings. This
      study describes the influence of an active community education program on
      changing physician behavior. METHODS: A total of 672 schoolteachers were
      interviewed and screened for detection of osteoporosis risk factors. The teachers
      were educated about osteoporosis and the significance of bone mass densitometry
      (BMD) in its management and returned to their physicians with the results of
      their screening. One group of their physicians received didactic lectures on the
      results of the screening and the impact of appropriate management on the outcome
      of osteoporosis. The second group of physicians did not. Six months after the
      initial interview and screening, patients received a mailed survey. RESULTS:
      After 6 months, 258 of the teachers who had visited their physicians were
      resurveyed. The percentage of BMD tests ordered by physicians rose from 8.6% to
      33% in both the intervention and control physician groups. Findings at the 6
      month survey indicated that physicians initiated the osteoporosis discussion an
      average of 18% of the visits and patients did an average of 60%, prompting the
      physician to order a BMD test. DISCUSSION: In this study, there was no evidence
      that didactic lectures affect physician behavior in ordering BMD. There were,
      however, compelling indications that patient education, which included written
      screening results, enhanced physician-patient dialogue, resulting in more BMD
      orders.

PMID- 12227237
TI  - Helping family physicians improve their cardiac auscultation skills with an
      interactive CD-ROM.
AB  - INTRODUCTION: There have been few studies of the cardiac auscultation skills of
      residents and family physicians. This study assessed a group of family
      physicians' cardiac auscultation skills and use of a computerized self
      instructional program to improve these skills. METHODS: Forty-two volunteer
      family physicians participated in an initial assessment of cardiac auscultation
      skills using test recordings of 12 common heart sounds. They were provided with a
      CD-ROM instructional program and were asked to devote 15 hours of self-study to
      the program and to return in 9 months for reassessment. RESULTS: The 42 family
      physicians in the initial assessment identified 39% of the heart sounds. Twenty
      one returned for reassessment and showed significant improvement. Their initial
      mean score was 4.3 of 12 (35%), and their final mean score was 8.0 of 12 (67%).
      They found the CD-ROM program to be a valuable resource. The feature most liked
      was the unlimited opportunity to review sounds, cases, and tutorials. Most
      frequent problems related to computer access or skills. Eleven respondents
      reported using the program to resolve patient problems in their clinical
      practices. DISCUSSION: The cardiac auscultation skills of a group of volunteer
      family physicians showed low initial scores that improved significantly after
      self-study with a CD-ROM instructional program. The program was a valuable self
      instructional aid, and physicians used it as a resource in clinical practice.
      However, only 50% of the initial group completed the self-study and returned for
      final assessment. Providing more support and assistance in the initial phase,
      especially with computer use, may enable completion of similar computerized self
      study programs.

PMID- 12227238
TI  - Educationally influential physicians: the need for construct validation.
AB  - INTRODUCTION: Educationally influential physicians may be a valuable resource in
      continuing medical education. Although the idea driving this research--informal
      learning--converges with research in adult education, organizational learning,
      marketing, and knowledge diffusion, the results of interventions have proven
      inconclusive. To actualize the promise of the educationally influential physician
      (EIP) construct, it is argued that researchers must return to the "classic"
      studies in this area and resume the process of validating the meaning of the
      construct. METHODS: A literature review and the occasion of an educationally
      influential physician identification survey provided an opportunity to contribute
      to development of this construct. We compared three identification rules used to
      study 212 physicians. RESULTS: Each rule may identify different people as EIPs.
      DISCUSSION: To improve the use of educational influentials, research must be
      completed to validate their role in informal learning.

PMID- 12227239
TI  - How rehabilitation therapists gather, evaluate, and implement new knowledge.
AB  - INTRODUCTION: Rehabilitation therapists are strongly encouraged to apply research
      to their practices, but relatively little is known about the processes therapists
      use for continuing their education. This study examines the strategies used by a
      sample of therapists to gather new knowledge, evaluate its appropriateness to
      their clinical problems, and implement new learning into their practices.
      METHODS: Twenty-four randomly selected occupational therapists and physical
      therapists from a large metropolitan area participated in in-depth interviews.
      Descriptive codes within interview transcripts described participants' individual
      approaches to continuing education (CE). Themes derived from comparative analysis
      across interviews were interpreted, building on prior understandings and
      suggesting strategies for CE research and programs. RESULTS: Participants valued
      formal CE highly and expressed frustration concerning its limited availability.
      Most participants relied on informal consultations with peers as their first
      educational resource. Peers also supported participants' evaluation and
      implementation of new knowledge. Although seven participants reported use of
      systematic methods to access, evaluate, and implement new knowledge, others
      described more haphazard approaches toward evaluation and application of their
      learning. Participants identified economic, administrative, and interprofessional
      barriers to integration of new knowledge into their practices. DISCUSSION: There
      is a need to develop and incorporate guidelines for evaluating and implementing
      learning within formal and informal CE programs. The appeal of formal CE suggests
      that more efficient strategies for continuing rehabilitation are required.
      Therapists' heavy reliance on peers suggests that educationally influential
      therapists may be effective media for informal CE interventions. CE targeted to
      policy makers should focus on promoting organizational change to enhance
      therapists' translation of research into practice.

PMID- 12227240
TI  - Establishing priorities for hospital education.
AB  - INTRODUCTION: Integrating the emerging evidence base for medicine, measuring
      quality of care, reducing medical errors, and understanding the managed care
      environment all present new challenges to the processes and outcomes of hospital
      education. Establishing priorities for hospital-based education is critical as
      cost containment measures influence education budgets. This article examines the
      learning modalities preferred by health care educators in their own educational
      experiences and the implications of preferences for newly emerging roles in
      hospital education. METHODS: To determine if a typology based on learning
      modalities has utility for helping health care educators establish priorities, a
      pilot study was conducted using three groups of health care educators. Subjects
      in the pilot study completed a questionnaire that asked them to list three
      examples of their most important recent learning experiences. RESULTS: Sixty-six
      subjects reported 181 learning experiences. These 181 learning experiences were
      divided into four learning modalities displayed in a 2 x 2 matrix based on
      "motivation" and "management" of learning as follows: 97 in problem solving, 52
      in training, 16 in schooling, and 16 in hobbying. DISCUSSION: From this study, it
      appears that problem solving is the prime learning modality of adults in health
      care, and departments of hospital education would be well advised to focus on
      practical learning and problem solving when developing their educational
      activities. This finding supports the use of selected modalities of education in
      meeting the new challenges of hospital education.

PMID- 12227241
TI  - At your service.

PMID- 12227242
TI  - Somewhat more than a splinter.

PMID- 12227243
TI  - Discussing basic principles for a coding system of drug-related problems: the
      case of PI-Doc.
AB  - Coding systems are important tools for the documentation of drug-related problems
      and following interventions. They should be suitable not only for scientific
      studies but for the broader implementation of Pharmaceutical Care in the
      pharmacy. A suitable coding system must be easy to use in daily routine. To
      facilitate later computer aided use, it should be preferably structured like a
      decision tree and consist of three parts: 1. the classification of drug-related
      problems 2. the intervention taken to solve to problem 3. the degree to which the
      problem was solved. PI-Doc considers other classification systems used by Hepler
      and Strand the PAS-Coding System and draws empirical experience from a study in
      1995 and 1998 in Germany. The main groups comprise the following: unsuitable drug
      choice unsuitable use by the patient, incl. compliance unsuitable dosage drug
      drug interactions adverse drug reactions other drug-related problems patient
      related communication-related technical and logistic problems. The article
      discusses basic principles of the development of a coding system and the
      prerequisites for its application. In addition, it tries to give guidance for the
      classification process itself. It is also recommended to collect further
      information while documenting drug-related problems, in order to allow additional
      statistical evaluation.

PMID- 12227244
TI  - Exploring the domains of appropriateness of drug therapy, using the Nominal Group
      Technique.
AB  - OBJECTIVE: To explore the domains encompassed within the assessment of the
      appropriateness of prescribing for an individual patient. METHOD: The Nominal
      Group Technique was used to address the question "How can we assess inappropriate
      drug therapy of individual patients that is responsive to pharmaceutical care?"
      The group participants were a self-selected group of nine pharmacists and one
      pharmacologist attending an international working conference on the Outcomes of
      Pharmaceutical Care. Item generation was followed by discussion for clarification
      and operationalization. Voting achieved a consensus, defined as > or = 70%,
      agreement on the importance of items for inclusion in an instrument to assess
      appropriateness. RESULTS: Sixty-seven items were initially generated. During
      discussion, similar items were combined and items were grouped into domains.
      Items that considered the patient's perspective were commonly suggested, but many
      were discarded after discussing their operationalization. Consensus was obtained
      that eighteen items, in seven domains, should be included in the instrument. The
      domains were indication and drug choice (5 items), effectiveness (2), risks and
      safety (2), dosage (3), interactions (1), practical use (4), and monitoring (1).
      CONCLUSION: It is hoped that, with adequate testing, these indicators of
      appropriateness of prescribing can be used by pharmacists to begin to routinely
      assess the impact of pharmaceutical care on the quality of prescribing for
      patients under their care.

PMID- 12227245
TI  - A systematic review of the clinical and economic impact of drug information
      services on patient outcome.
AB  - AIM: To establish what is known about the clinical and economic impact of drug
      information (DI) services on patient outcome. METHOD: A systematic review and
      critical appraisal of world literature on work conducted by Drug Information
      Centres and UK Schools of Pharmacy. RESULTS: Six relevant published articles were
      recovered--three from the UK; two from the US and one from Canada; just one was
      prospective in design. Four were single-centre and two were multi-centre studies.
      Four studies relied heavily on questionnaire surveys of the enquirer to establish
      an effect; only one monitored patient outcome independently and used peer review
      to assess impact. CONCLUSION: The clinical and economic impact of drug
      information consultation and provision on patient care has not been investigated
      rigorously. A research methodology for such an investigation is suggested.

PMID- 12227246
TI  - Pharmacy representatives: a non-pharmacy outlet of prescribed medicines in
      Sweden.
AB  - OBJECTIVE: To characterise patients who collect their prescribed medicines from
      pharmacy representatives and compare them with those using regular pharmacies.
      METHOD: Data were collected from the prescriptions delivered via pharmacy
      representatives and by questionnaires to the patients. Data for pharmacies were
      obtained from the Swedish drug statistics. The data were used to determine gender
      and age of the patients and the types of drugs delivered from the pharmacies and
      from the pharmacy representatives. SETTING: Pharmacy representatives connected to
      20 randomly selected pharmacies in Sweden. KEY FINDINGS: Prescriptions were
      analysed with respect to the patients' gender, age and prescribed medicine(s).
      The proportion of elderly patients (> or = 75 years) as greater among users of
      pharmacy representatives than among pharmacy users (40% compared to 24%), but in
      most other respects the two patient groups were similar. Patients used pharmacy
      representatives because it was more convenient, and only 5% of patients using
      pharmacy representatives had called the pharmacy to ask how their medicine should
      be used. CONCLUSIONS: Patients using the pharmacy representatives may serve as
      reference groups in studies of the effect of pharmaceutical care interventions.
      Only a small number of these patients receive any advice from the pharmacists and
      this may have a negative effect on adherence and therapy outcome.

PMID- 12227247
TI  - Evaluation of patient outcomes in an area where prescribing of anticholinergic
      antidepressants was influenced by academic detailing.
AB  - OBJECTIVE: To evaluate, on a patient level, the effect of a "physician-level
      intervention" that successfully reduced the incidence of anticholinergic
      antidepressant prescribing. DESIGN: Cross-sectional surveys with questionnaires
      sent before and after intervention. SETTING: Additional study in an RCT to reduce
      the prescribing of highly anticholinergic antidepressants in the elderly in the
      South Holland Islands. PARTICIPANTS: Elderly patients (age 60-95 years) who used
      antidepressants in 1995 and 1996 in our research area according to a health
      insurance prescription database. MAIN OUTCOME MEASURES: Prevalence of adverse
      events related to antidepressant use, severity of depression and quality of life
      were compared in users living in the intervention and control areas. RESULTS:
      Prior to our intervention we sent 2,359 questionnaires of which we could use 827
      (35%) for analysis. At baseline, there were no statistically significant
      differences between the intervention and control areas. After the intervention
      3,375 questionnaires were sent, of which 939 (28%) could be used. The occurrence
      of "dry mouth" and "coughing" and the "amount of pain" were lower in the
      intervention area compared to the control area (p < 0.05). CONCLUSION: We found
      no indications that adverse events, severity of depression or quality of life
      were changed in an unfavourable direction, when comparing patients inside and
      outside the intervention area.

PMID- 12227248
TI  - Purchasing restricted medicines in New Zealand pharmacies: results from a
      "mystery shopper" study.
AB  - OBJECTIVE: New Zealand has a class of drugs (Restricted Medicines) which are
      available over the counter in pharmacies, but must be sold by qualified
      pharmacists. Patient names must be recorded for each sale. Many restricted
      medicines have recently been reclassified from prescription only, with the
      expectation that pharmacists provide professional input into their sale. The
      study described here explored whether pharmacists do fulfill this expectation.
      METHOD: In late 1999, 12 mystery shoppers made 360 visits to 180 pharmacies
      around New Zealand. Shoppers were of different ages, genders, ethnic and socio
      economic backgrounds. Two kinds of products were purchased: diclofenac 25 mg,
      which was requested for "back pain" and vaginal anti-fungals requested for
      "thrush". MAIN OUTCOME MEASURE: The main outcome measure described here is
      whether the shoppers received specified items of counselling. These included
      questions about the shopper's health status, contraindications to medicine use,
      advice about the use of the product and the health problem presented. Other
      outcome measures are whether sales of restricted medicines were carried out by
      pharmacists or other staff, and whether sales were recorded. RESULTS: In spite of
      the requirement that pharmacists sell restricted medicines, shoppers often found
      it difficult to distinguish pharmacists from other pharmacy staff. Shoppers were
      able to confirm that a pharmacist was definitely involved in only 46% of visits.
      In 8.8% of the diclofenac visits, and 10.8% of the visits for vaginal anti
      fungals, no counselling was provided. The vaginal anti-fungal visits tended to be
      more product-focussed than the diclofenac visits. When they purchased diclofenac,
      most pharmacists asked shoppers if they had, or had had, stomach problems (74.6%)
      or asthma (65.4%). A minority asked about the symptoms of the vaginal fungal
      infection which the female shoppers presented with. While most pharmacies
      recorded patient names, many did so in a way which compromised patient
      confidentiality. CONCLUSION: Pharmacies varied widely in the amount of
      counselling they provided to people purchasing restricted medicines.

PMID- 12227249
TI  - Patient oriented activities in Dutch community pharmacy: diffusion of
      innovations.
AB  - OBJECTIVES: To explore the implementation of patient oriented activities, the
      perception of an innovation aimed at implementation of patient education and the
      preconditions for implementation of this innovation among Dutch pharmacists.
      METHOD: A survey, based on Roger's theory of diffusion of innovations, was
      carried out among a random sample (n = 300) of Dutch managing pharmacists. MAIN
      OUTCOME MEASURES: Reported activities regarding patient education, medication
      surveillance and drug therapy meetings, as well as perception of the innovation
      and its perceived compatibility with pharmacy practice. RESULTS: The response
      rate was 49.3%. Hundred (84.7%) respondents reported to provide extra written and
      verbal information with first prescription medication. Medication surveillance
      (100% check by computer, and check of the lists by the pharmacist) was reported
      by 43 (36.4%), and complete participation in drug therapy meetings was reported
      by 57 (48.3%) respondents. Observability (or results to others) of the new
      strategy was perceived as important by 90 (77.6%), compatibility (perceived
      consistency with existing values, past experiences and needs of potential
      adopters) by 87 (76.4%) and trialability (degree to which an innovation may be
      experimented with) by 81 (69.8%) respondents. Relative advantages (perception of
      the innovation as being better) and complexity (relatively difficult to
      understand and use) of the innovation were perceived as important by less
      respondents. The preconditions that were met by most pharmacists were 'financial
      resources' (n = 70; 59.8%), 'enough workspace' (n = 61; 53.1%) and 'enough time'
      (n = 58; 50%). Fifty-eight (49.2%) respondents intend to adopt the innovation,
      but this intention would be higher when more time and money and technicians are
      available, as well as less situations that are experienced as barriers (rush
      hours, lack of support, illness of employees). CONCLUSION: Based on the
      definitions used, we conclude that the implementation of medication surveillance
      and drug therapy meetings is relatively low compared to patient education. The
      development of an implementation tool is justified, but should deal with the
      experienced preconditions, barriers and needs of pharmacists. Combined,
      comprehensive pharmacy interventions promise to be a good way to change pharmacy
      practice.

PMID- 12227250
TI  - Anti-asthmatic drugs and dosage forms in children: a cross-sectional study.
AB  - OBJECTIVE: To describe the choice of drugs as well as the dosage forms of anti
      asthmatic drugs in children with regard to different age groups. METHODS: Cross
      sectional study based on computerized pharmacy dispensing records of 1999 for
      children aged 0-16 years in the north of the Netherlands. All children were
      selected and divided in the following age groups: 0-1, 2-5, 6-11 and 12-16-year
      olds. RESULTS: Inhaled beta 2-agonists and inhaled corticosteroids were the most
      widely used anti-asthmatic drugs in all age groups (respectively 59 and 58 users
      per 100 anti-asthmatic using 0-16 year-olds). Cromones were rarely used. Up to
      four years of age the use of treatment with aerosol inhalers increased
      simultaneously with a decrease of oral dosage forms. The use of dry powder
      inhalers started at the age of approximately 4 years old and increased to about
      85% of the users at the age of 11, with the strongest increase around the age of
      6 and 7. CONCLUSION: The choice of drugs and dosage forms corresponds with what
      might be expected based on guidelines for the treatment of asthma in children,
      except for the high use of deptropine in the youngest age group. Anti-asthmatic
      drugs for preventive treatment are used so frequently without beta 2-agonists
      that questions about possible overtreatment need to be raised.

PMID- 12227251
TI  - [How does one explain the very good performance of Spanish nephrology].
AB  - Spain is a highly performing country in nephrology with 2000 kidney grafts a year
      (50 pmp); 42% of end stage renal disease patients have a functioning kidney graft
      (338 pmp); the highest level worldwide of organ donors (33.9 pmp) and very few
      living donors and finally one of the lowest level in Europe of "late referral to
      nephrologists" (18%). Amongst various explanations emerge the fact that the
      number of nephrologist is high in this 40 millions inhabitants country (more than
      one thousand) when they are less than the thousand for 60 millions inhabitants in
      France.

PMID- 12227252
TI  - [Oxidative stress, hemo-incompatibility and complications of long-term dialysis].
AB  - Oxidative stress which results from an imbalance between oxidant production and
      antioxidant defense mechanisms is now a well recognized pathogenesis factor that
      could be implicated in the hemodialysis (HD)-related pathology. This review
      focuses on: 1) factors that may be responsible for oxidative stress in HD
      patients (hemoincompatibility of the dialysis system--hemoreactivity of the
      membrane and trace amounts of endotoxins- and uremia per se); 2) implication of
      such phenomenon in long term complications including anemia, amyloidosis,
      accelerated atherosclerosis and malnutrition and finally and 3) prevention ways
      consisting in improving the hemocompatibility of the dialysis system and
      supplementing the deficiency patients with antioxidants.

PMID- 12227253
TI  - [Role of the Na(+)-K+(NH4+)-2Cl cotransporter of the medullary ascending limb in
      the regulation of renal acid-base equilibrium].
AB  - NH4+ absorption by the medullary thick ascending limb (MTAL) of Henle's loop,
      which causes the accumulation of NH4+/NH3 in the medullary interstitium, is a key
      step in the renal handling of ammonia. Accumulation of NH4+/NH3 in the medullary
      interstitium is necessary to the secretion of ammonia in the medullary collecting
      ducts and then to NH4+ excretion in the urine. The MTAL apical Na(+)-K+(NH4+)-2Cl
      cotransporter BSC1/NKCC2 is responsible for the majority of the MTAL luminal
      NH4+ uptake. Stimulation of BSC1 expression by metabolic acidosis accounts for
      the increase of the MTAL ability to absorb NH4+ during this condition. Metabolic
      acidosis increases the mRNA and protein abudance and the transport activity of
      BSC1. Two factors have been demonstrated to mediate the effects of acidosis, an
      acid pH and glucocorticoids whose production augments during metabolic acidosis.
      These two factors thus control in a coordinated manner ammoniagenesis in the
      proximal tubule and MTAL NH4+ transport to ensure urinary acid excretion rates
      appropriate to the acid-base status.

PMID- 12227254
TI  - [Renal amyloidosis secondary to hydatid cyst of the liver. Clinical remission
      after surgical excision].
AB  - Revelation or risk of aggravation of renal amyloidosis after surgery has been
      published, particularly after pneumonectomy for tuberculosis. A few cases of
      improvement of renal amyloidosis following treatment of amylogenic focus have
      been published. We report the case of a 57 year-old woman who presented with
      nephrotic syndrome occurred twenty days after surgical resection of an hydatid
      cyst of the liver secondary to echinococcus granulosus. The renal biopsy showed
      deposits of amyloidosis. Amyloidosis typing (using anti AA sera) revealed an AA
      type. The patient received colchicine during nine years. A complete clinical
      remission of nephrotic syndrome was obtained four years after the surgical act.
      We discuss the association of hydatidosis and amyloidosis, surgery and
      amyloidosis, and remission of renal amyloid and colchicine therapy.

PMID- 12227255
TI  - [Regulation of the luminal Na+/H+ exchanger NHE3 by intracellular protein
      trafficking].
AB  - The article summarizes some of the recent developments in the understanding of
      the mechanisms of regulation of the proximal tubule apical membrane Na+/H+
      antiporter NHE3. NHE3 antiporter has a major role in HCO3- and NaCl reabsorption
      in the proximal tubule. NHE3 protein is associated with the regulatory factor
      NHERF which interacts with ezrin, an actin-binding protein. This multi-protein
      complex constitutes a link between a membrane protein, NHE3, and actin
      cytoskeleton. Cytoskeleton organization has a key role to control NHE3 activity
      under normal conditions. Pharmacological perturbations of actin polymerization
      interfere with NHE3 activity. Parathyroid hormone-induced NHE3 activity
      inhibition results first, from a protein kinase A-mediated phosphorylation
      without protein trafficking, and then from endocytosis involving dynamin. The
      stimulatory effect of systemic angiotensin II concentrations on NHE3 activity is
      protein kinase C-dependent and results, at least in part, from exocytic insertion
      of the protein in luminal membranes. It requires cytoskeleton integrity.

PMID- 12227256
TI  - Progress towards poliomyelitis eradication. Angola, January 1998-June 2002.

PMID- 12227257
TI  - "She drank his money": survival sex and the problem of violence in taverns in
      Gauteng province, South Africa.
AB  - This article examines the practice of "survival sex" in the taverns of Soweto and
      Hammanskraal area, South Africa. Women who engage in survival sex do not self
      identify as commercial sex workers, and the community does not identify them as
      such. Those who structure HIV prevention programs should not confound such women
      with commercial sex workers, because effective intervention may vary between the
      two groups. Violence against women who engage in survival sex in taverns is
      common, as it is argued that, when a woman accepts beer from a man, she is
      obliged to exchange sex (because she has "drunk his money"). The South African
      government should prioritize the reduction of violence as a way to reduce HIV
      transmission, as, in the context of violence, women do not have the option of
      negotiating safer sex.

PMID- 12227258
TI  - Kunyenga, "real sex," and survival: assessing the risk of HIV infection among
      urban street boys in Tanzania.
AB  - This article examines possible avenues of HIV infection among urban street boys
      in Tanzania. In doing so, it questions the ways that AIDS researchers have
      defined and approached the phenomenon of "survival sex" in East and Central
      Africa. The article specifically examines the boys' sexual networks, sexual
      practices, and attitudes regarding their own sexual behavior, including their
      perceived risk of HIV/AIDS infection. Seventy-five street boys aged eight to 20
      from the city of Mwanza were interviewed. Results suggest that almost all street
      boys are involved in a sexual network in which homosexual and heterosexual
      behavior occurs. Homosexual practices are rooted in a complex set of behaviors
      and ideologies known as kunyenga, which is a situated aspect of life on the
      streets and helps maintain the boys' strong dependence on one another. A key
      aspect of the boys' sexual careers involves a decrease in kunyenga activity as
      they approach the age of 18 and an increase in heterosexual encounters after the
      age of 11. There appears to be a critical period between these ages in which
      heterosexual and kunyenga activities overlap. It is suggested that boys between
      these ages represent a potential bridge for HIV/AIDS infection between the
      general population and the relatively enclosed sexual network of street boys.

PMID- 12227259
TI  - Pain as a counterpoint to culture: toward an analysis of pain associated with
      infibulation among Somali immigrants in Norway.
AB  - This article focuses on how some Somali women experience and reflect on the pain
      of infibulation as a lived bodily experience within shifting social and cultural
      frameworks. Women interviewed for this study describe such pain as intolerable,
      as an experience that has made them question the cultural values in which the
      operation is embedded. Whereas this view has gone largely unvoiced in their natal
      communities, the Norwegian exile situation in which the present study's
      informants live has brought about dramatic changes. In Norway, where female
      circumcision is both condemned and illegal, most of the women have come to
      reconsider the practice--not merely as a theoretical topic or as a "cultural
      tradition" to be maintained or abolished but, rather, as part of their embodied
      and lived experience.

PMID- 12227260
TI  - Narrative mediation of conventional and new "mental health" paradigms: reading
      the stories of immigrant Iranian women.
AB  - The potential of storytelling to effect change and produce new knowledge is being
      recognized across disciplines. Two conditions are necessary to realize these
      goals: first, reading of stories must be contextualized to include larger social
      and political landscapes; and second, how stories are read and toward what end
      must be closely examined. This article explores these issues with reference to
      the subject of the "mental health" or emotional well-being of a cohort of
      postrevolution Iranian women from metropolitan Vancouver, British Columbia.
      Reading their stories at a particular moment in time shows that well-being is
      essentially grounded in spaces and places where we live, work, and engage in
      social interactions. This commonplace knowledge, which is subdued in medical
      discourse, is retrieved through Iranian women's stories of life and living told
      at a time when their experiences, histories, and viewpoints on health are subject
      to erasure.

PMID- 12227261
TI  - The role and meaning of susto in Mexican Americans' explanatory model of type 2
      diabetes.
AB  - This article examines the role and meaning of susto (fright) in Mexican
      Americans' explanatory model (EM) of type 2 diabetes. This analysis is based on a
      study of the health beliefs about type 2 diabetes mellitus among Mexican
      Americans living in El Paso County, Texas, on the U.S.-Mexico border. Susto was
      described as an event that could change the bodily state, causing a susceptible
      person to be more vulnerable to the onset of type 2 diabetes after some
      unspecified time. The study results illustrate the integration of multiple
      etiologies into Mexican Americans' EMs of diabetes and illustrate how the
      environment affects the way in which these explanations are manifested.
      Acculturation of biomedical system beliefs into the traditional Mexican health
      belief system has resulted in a synthesis of both systems and a blending of the
      participants' explanation of type 2 diabetes.

PMID- 12227262
TI  - Congressional earmarks and pork barrel politics.

PMID- 12227263
TI  - Prevalence and determinants of burnout among physical and occupational
      therapists.
AB  - It is generally speculated that the ongoing changes in the health care system may
      increase the incidence of burnout among health care providers. The purposes of
      this cross-sectional study were to determine (1) the prevalence of burnout among
      physical therapists (PTs) and occupational therapists (OTs), (2) sociodemographic
      and work-related factors associated with emotional exhaustion (EE),
      depersonalization (DP), and personal achievement (PA) traits of PTs and OTs. In
      fall 1998, 169 PTs and 138 OTs employed in various clinical settings in New York
      City completed the survey. Part I of the research questionnaire solicited
      sociodemographic and work-related information such as age, marital status, number
      of children (NC), religious affiliation (RA), exercise habits, level of support
      from supervisor (LSS), and level of support from colleagues (LSC). Part II of the
      questionnaire contained the Maslach Burnout Inventory (MBI). From the MBI, each
      subject's EE, DP, and PA scores were obtained. The data were analyzed with oneway
      analysis of variance and linear, multiple, and stepwise regression models to
      determine the relative and combined contributions of the independent
      (sociodemographic and work-related) variables toward predicting EE, DP, and PA.
      Overall the MBI scores revealed high (28.9 +/- 6.8) EE, high (18.3 +/- 4.7) DP,
      and low (18.0 +/- 7.0) PA. The contribution of sociodemographic and work-related
      variables toward the prediction of EE (26.7%), DP (12.8%) and PA (19.8%) was
      minimal. Of the 20 independent variables examined in this study, only 3 (LSS, NC
      and RA) were viable predictors of EE. The only viable predictor of PA trait was
      LSC. None of the variables examined accurately predicted DP trait. The EE, DP,
      and PA scores of the PTs and OTs in this study were higher than the norms
      reported in previous studies for the general population and other human service
      professionals, including PTs and OTs. The findings suggest the need for
      reorganization of the work environment to address the stressors responsible for
      burnout in this cohort of therapists.

PMID- 12227264
TI  - Depression and associated characteristics among community-based elderly people.
AB  - Depression is a major health problem, particularly among the elderly. It is
      important that allied health professionals, especially those working with the
      elderly, understand this often serious condition. The data for this article were
      collected as part of an interdisciplinary geriatric health care team project,
      which included allied health professionals working in rural and urban clinics.
      The primary purpose of this study was to determine the association of depression
      with various demographic, medical, mental, physical functionality, and social
      factors among community-based elderly people. A logistic regression (backward
      selection) indicated that elderly people living alone were 3.3 times more likely
      to be depressed than elderly residing in a household with others. As assistance
      with instrumental activities of daily living increased, the likelihood of
      depression also increased. Most significantly, urban residents were 3.8 times
      more likely to be depressed than their rural counterparts. Additional research
      into the differences in the prevalence of depression between urban and rural
      elderly would provide a more in-depth understanding of this problem and help to
      identify more effective treatment plans for different elderly populations. Other
      independent variables, including demographic, medical, and social characteristics
      were not found to be significantly predictive of depression in this study.

PMID- 12227265
TI  - Chaos theory as a planning tool for community-based educational experiences for
      health students.
AB  - Educational and community health systems are social systems composed of a group
      or collection of entities for which there is a unifying principle. The purpose of
      this paper is to briefly explain chaos theory and to apply it to the
      Interdisciplinary Rural Health Training Program (IRHTP) as a case study. The
      IRHTP is an existing rural, community based educational program for baccalaureate
      and graduate health care students. Chaos theory attempts to understand the
      underlying order in processes that appear to not have any guidelines or
      principles. These processes typically involve the interaction of several elements
      over time. Chaos theory provided the university with a method of anticipating the
      natural flux between order and chaos to allow the system to function at its
      highest level. To thrive in such a complex dynamic environment the authors
      recommend application of Ockerman's Five Factors.

PMID- 12227266
TI  - Assessment outcomes: computerized instruction in a human gross anatomy course.
AB  - New and traditional educational media were used to study alternative methods of
      instruction in a human gross anatomy course. Three consecutive entry-level
      physical therapy (PT) classes (55 students total) participated in this study. No
      other anatomy course was available to these students during this time. During the
      first year, all entering PT students (n = 18) completed a traditional cadaver
      anatomy course. This traditional group attended weekly lectures and dissection
      laboratories for 15 weeks. During the second year, the next entering class of PT
      students (n = 17) completed a self-study, computerized noncadaver anatomy course.
      This self-study group attended an introductory session to receive course
      objectives and instruction in using the computer package chosen for the study.
      After the introductory session, this group worked independently for the remainder
      of their 15-week course. During the third year, the entering class of PT students
      (n = 20) attended weekly lectures and completed a self-study, computerized non
      cadaver laboratory course. This lecture and self-study group attended an
      introductory session to review course objectives and receive instruction in using
      the computer package. For the remainder of their 15-week course, this group
      attended a weekly lecture and worked independently on the computer for the
      laboratory portion of their course. All groups kept time logs, recording class
      and study time for each day of the course. The time logs were collected on the
      last day of each course. Each group's performance in anatomy-based system courses
      was followed through the remainder of the PT curricula, including clinical
      rotations, and through the completion of the state board licensure examination.
      Data were analyzed using a multivariate analysis of variance and a Kruskal-Wallis
      analysis of variance. There was no significant difference in anatomy course class
      means, class study times, performance throughout the remainder of the PT
      curricula, and performance on the state board licensure examination. The results
      of this study suggest that computerized self-study techniques may be a viable
      alternative to traditional cadaver laboratory and instruction in human gross
      anatomy courses. Plans for future study include the continued use of lecture and
      computerized study and the use of a supplemental bone and radiology laboratory.

PMID- 12227267
TI  - Effective patient education in medical imaging: public perceptions of radiation
      exposure risk.
AB  - Patients perceptions of risk for harm influence their decisions concerning
      medical procedures and feelings of satisfaction with medical care choices.
      Radiologic technologists, dental hygienists, and other allied health
      professionals frequently are asked by patients to explain the radiation exposure
      dose and health risk associated with an imaging procedure. The purpose of this
      study was to evaluate the radiation risk perceptions within the community to
      develop an effective patient education strategy for health professionals based on
      the responses of 200 participants in a cross-sectional survey. Less than half of
      the adults responding to the survey agreed with experts regarding the risk of
      radiation exposure from various sources, and 75% to 90% of the responders thought
      that imaging providers should be highly educated and highly regulated. With
      efficacious patient education, appropriate risk comparisons can be made in simple
      terminology by addressing the public's knowledge, beliefs, and attitudes toward
      sources of radiation exposure.

PMID- 12227268
TI  - International allied health education and cross-cultural perspectives.
AB  - International partnerships develop long-lasting friendships among colleagues.
      This is a dividend that is of immense value in this otherwise terribly divided
      globe with health care issues being a major concern. The framework and lessons
      learned proposed herein should be of value to individuals in colleges and
      universities to promote a true learning experience for both partners that are
      enduring and replicable models of international cooperation.

PMID- 12227269
TI  - Family mentoring: a life experience.
AB  - The purpose of this study was to determine the effectiveness of a preservice
      education family mentor experience on the development of family-centered
      attitudes expressed by 84 nursing, occupational therapy, physical therapy, and
      social work students from a private Midwestern university. The instrument, Issues
      in Early Intervention, was administered to students before and after
      participation in a field experience that included a minimum of 8 hours with
      assigned families. The instrument measured changes in attitude regarding family
      centered care expressed by students in response to 24 statements reflective of
      family-centered concepts and approaches. A Wilcoxon signed rank test was used to
      analyze data from pretests and posttests using the Issues in Early Intervention
      instrument. Eight items reflected significant positive changes in family-centered
      attitudes. When total scores were examined using a paired t-test, students
      demonstrated a significant increase (p < or = 0.001) in family centered attitudes
      after the family mentor experience according to the instrument. The family mentor
      experience evaluation of outcome objectives was administered to students at the
      conclusion of the project. Results from student feedback on the family mentor
      experience evaluation of experience outcomes also indicated a positive impact in
      family-centered attitudes as a result of the family mentor experience.

PMID- 12227270
TI  - [To peel or not to peel... ...and further questions on the management of macular
      holes].

PMID- 12227271
TI  - [Macular holes. Review of the current status of knowledge of pathogenesis and
      treatment methods].
AB  - This article is based on the author's personal views and clinical experience and
      offers an overview of the current state of knowledge on the pathogenesis of
      macular holes including currently available therapy strategies. Special attention
      is paid to the prevailing controversial issues regarding treatment concepts for
      macular holes.

PMID- 12227272
TI  - [Macular holes. A treatable disease picture with unsolved problems].
AB  - Macular holes have a special position in the paradigmatic change of vitreoretinal
      surgery during the past 10 years. While the rationale for existence of retinal
      and vitreal surgery is based largely on invasive mechanical intervention in cases
      of large-surface epiretinal tractions, e.g., in diabetic traction amotio or
      detached retina with PVR, the intention of surgical treatment for macular holes
      is to employ a minimally invasive method, using less direct mechanical
      manipulation and taking into consideration physical and cell biological aspects
      to induce local repair processes. Whereas the classification according to Gass is
      still completely based on the perspective of epiretinal traction via retracted
      vitreal material, newer theories, relying on more subtle diagnostic examination
      techniques, assume a complex interaction of tractive and proliferative effects.

PMID- 12227273
TI  - [The relationship between retrobulbar blood flow velocity and glaucoma damage. An
      intraindividual comparison].
AB  - BACKGROUND: Glaucomatous optic nerve damage is thought to be influenced by ocular
      perfusion. The aim was to investigate if a difference in visual field and
      Heidelberg retinal tomography (HRT) between two eyes of an individual glaucoma
      patient is reflected in different blood flow velocities in retrobulbar vessels.
      METHODS: Data from 53 patients including 26 normal tension glaucoma patients
      (NTG) and 27 high tension glaucoma patients (HTG) were evaluated retrospectively.
      In 38 patients asymmetric glaucomatous damage (AGD) could be demonstrated by both
      structural (HRT) and functional measures (static or Goldmann perimetry). In 15
      patients there was symmetric glaucomatous damage (SGD). To discriminate between
      AGD and SGD we used a score for HRT and visual field. Color Doppler imaging (CDI)
      was performed with a Siemens Quantum 2000. RESULTS: No significant differences
      were found when comparing group means of intraindividual deviation of CDI in
      patients with AGD vs. SGD. Overall analysis of CDI values in NTG vs. HTG eyes
      also showed no significant differences. Nevertheless we measured decreased blood
      flow velocities for NTG compared to HTG eyes especially in short posterior
      ciliary arteries, peak systolic and end diastolic velocities. CONCLUSIONS: A
      simple correlation between retrobulbar blood flow velocities and glaucomatous
      damage could not be found. However, color Doppler images can give important
      additional information in the diagnosis of glaucoma, especially normal tension
      glaucoma.

PMID- 12227274
TI  - [Indocyanine green angiography in choroid metastases].
AB  - BACKGROUND: Up to now the diagnosis of choroidal tumors was mainly based on
      ophthalmoscopy and ultrasound examination. Indocyanine green angiography allows
      the identification of vascular patterns in these tumors, which could be helpful
      in the differential diagnosis. The aim of the study was to characterize the
      staining patterns of choroidal metastases. METHODS: In the years 1996-2000 we
      performed ICG-A of 15 choroidal metastasis using the scanning laser
      ophthalmoscope from Rodenstock. The mean tumor height was 3.7 mm (2.0-9.0). These
      angiographies were compared to the angiographies of 38 choroidal malignant
      melanomas with a mean height of 3.6 mm (1.4-6-6). RESULTS: All metastases showed
      a blockage of the background staining and a patchy staining of the tumor surface.
      Intratumoral vessels could be detected in 13% of all cases of metastases. The
      choroidal melanomas examined showed a blockage of the background staining in all
      cases and tumor vessels in 89%. CONCLUSION: The angiographic picture of the
      metastatic lesions was characteristic. Intratumoral vessels could not be detected
      using ICG-A. Most of the metastases showed a patchy staining of the tumor
      surface.

PMID- 12227275
TI  - [Photodynamic therapy of subfoveal choroid neovascularization. Analysis of
      fixation behavior].
AB  - BACKGROUND: In a prospective, randomized, placebo-controlled clinical trial, we
      have analyzed the pattern of fixation in patients with subfoveal choroidal
      neovascularization in age-related maculopathy, who have been treated with
      photodynamic therapy (Verteporfin). MATERIALS AND METHODS: The patients in this
      study were participating in the TAP trial at a study center (Lubeck). The TAP
      study inclusion criteria have been applied and photodynamic therapy was carried
      out by the TAP study standard protocol. For microperimetric analysis we used the
      Scanning Laser Ophthalmoscope 101 (Rodenstock). Fixation was classified into
      foveal and excentric fixation. In addition we quantified the area of fixation
      (mm2). All patients had a follow-up of 2 years. RESULTS: Out of 33 patients in
      the Verteporfin group, 29 showed central fixation at baseline and only 11 out of
      33 had foveal fixation after 24 months. The area of fixation in this group was
      measured at baseline at 0.44 mm2, at 1.76 mm2 after 6 months and at 2.4 mm2 after
      12, 18 and 24 months, respectively. In the placebo group 11 out of 13 patients
      had foveal fixation at baseline and after 24 months 2 out of 13 demonstrated
      central fixation. The area of fixation increased from 0.76 mm2 at baseline up to
      2.4 mm2 after 6 months, to 4.9 mm2 after 12 months, to 7.1 mm2 after 18 months
      and finally after 24 months up to 9.61 mm2. CONCLUSIONS: Photodynamic therapy
      with Verteporfin does not prevent loss of central fixation in patients with
      subfoveal choroidal neovascularization in age-related maculopathy, however PDT
      has a significant stabilizing effect on the development of the area of fixation.

PMID- 12227276
TI  - [HLA class I antigen expression correlates with histological cell type in uveal
      melanoma].
AB  - PURPOSE: The prognosis of uveal melanoma is correlated with its histologic cell
      type. The epithelioid cell type is associated with a higher metastatic rate than
      the spindle cell type. The Human Leucocyte Antigen Class I (HLA-I) expression of
      the melanoma also correlates with the prognosis. In this study, we analyzed HLA-I
      antigen expression of uveal melanomas to determine whether a relationship exist
      between antigenic expression and melanoma cell type. METHODS: Formalin-fixed,
      paraffin-embedded spindle cell type (n = 11) and epithelioid cell type (n = 11)
      uveal melanomas were immunostained with the HC10 antibody (1:80) for HLA-I
      antigen expression with appropriate positive and negative controls. Sections were
      assessed semiquantitatively according to the percentage of stained cells.
      RESULTS: Among the spindle cell type melanomas, 2 out of 11 (18%) stained with
      HC10 antibodies. The staining intensity was less than 25% of the cells in these
      two melanomas. Among the epithelioid cell type melanomas, 9 out of 11 (82%)
      stained with HC10. The staining intensity was more than 25% of the cells in 5 of
      these 9 melanomas. CONCLUSIONS: It is unknown why spindle and epithelioid cell
      type uveal melanomas have different prognoses. Human uveal melanoma cell lines
      with low HLA-I expression are susceptible to NK cell-mediated lysis in vitro and
      in murine studies. The prognostically more favorable spindle cell type melanoma
      expresses less HLA-I than the epithelioid cell type melanoma. These results
      stress the role of NK cells in the rejection of uveal melanoma.

PMID- 12227277
TI  - [Scientific evaluation and quality assurance in refractive surgical
      interventions. Evaluation of the Datagraph med computer program].
AB  - BACKGROUND: During recent years refractive surgical procedures have been
      increasingly used to correct refractive errors. Exact saving and assessment of
      pre-, intra- and postoperative results for scientific evaluation are desired and
      are necessary for quality management. The purpose of this investigation was to
      evaluate the database program Datagraph med (version 2.5) which has been
      developed for data processing and assessment in refractive surgery. MATERIAL AND
      METHODS: Pre-, intra- and postoperative data of 169 eyes treated with different
      refractive surgical methods (laser in situ keratomileusis, photorefractive
      keratectomy, laser thermal keratoplasty, phacic IOL) were collected, entered in
      the database and then evaluated by the above-mentioned program (with a follow-up
      of up to 12 months). The exactness of the Datagraph results was compared by means
      of manual recalculation. RESULTS: Datagraph med was able to precisely process the
      patient data and save them in a database. Statistics and graphs presented by
      Datagraph were as data has been entered. Furthermore all standard graphs
      requested by the international consensus for evaluation of refractive surgical
      data (stability, predictability, efficacy, safety and complications) could be
      imaged. CONCLUSIONS: Datagraph med is a helpful and precisely functioning program
      for processing and evaluation of refractive surgical data. It can be used for
      both scientific studies and for quality control. A continuous development and
      improvement of the program as well as the addition of statistical functions will
      be necessary due to the on-going progress in refractive surgery.

PMID- 12227280
TI  - [Striae in the flap after laser in situ keratomileusis. Etiology, diagnosis and
      treatment].
AB  - OBJECTIVE: Laser in situ keratomileusis (LASIK) has become the leading refractive
      option to correct myopia, hyperopia and astigmatism. In addition to the relative
      rapid visual recovery and the lack of postoperative pain, new flap-related
      complications are being added. The formation of striae can lead to a significant
      loss of corrected visual acuity if the central pupil zone is affected. Awareness
      of possible complications is important not only for the surgeon, but also for the
      ophthalmologist in practice for a rapid diagnosis and prompt management. CLINICAL
      COURSE AND THERAPY: Striae have a variety of appearances and are caused by
      misalignment/displacement of the corneal flap after replacement or are results of
      a slippage effect of the flap over the stromal bed after LASIK. Symptomatic
      striae ideally are treated on the first or second day after surgery by refloating
      the flap, irrigation with balanced salt solution or hypotonic saline solution,
      stroking and stretching the surface with moist and dry sponges. In more severe
      cases scraping away the epithelium and antitorque or interrupted sutures can be
      performed to treat persistent striae. CONCLUSION: Symptomatic deep striae should
      be diagnosed early and managed promptly within the first days. Any later
      intervention decreases the chance of successful elimination and visual outcome.
      Hints to prevent the development of striae formation are provided.

PMID- 12227278
TI  - [Genetic studies of age related macular degeneration].
AB  - While during the 1980s epidemiological studies searched for possible associations
      of environmental factors, factors of lifestyle, and cardiovascular diseases with
      age-related macular degeneration (ARMD), this is now perceived as a
      multifactorial disorder with predisposing genetic constellations and with
      environmental factors contributing to disease progression. The evidence which
      supports a genetic background of ARMD comes from population-based studies as well
      as from familial aggregation and twin studies. Meanwhile, the knowledge about the
      genetics of ARMD has increased, however, the search for the genetic basis faces
      challenges and due to the late onset there is usually only one generation
      available for studies. Moreover, uncertainty surrounds the diagnosis in previous
      generations but nonetheless, ARMD is clinically heterogeneous and some ambiguity
      exists concerning the earliest signs. In this article, the current state of
      genetic research into ARMD as well as the techniques to approach this complex
      disorder will be discussed.

PMID- 12227279
TI  - [Follow-up of proliferation of juxtapapillary retinal pigment epithelium].
AB  - PURPOSE: Bengin proliferation of the juxtapapillary retinal pigment epithelium is
      a rare but important tumor because it may be mistaken for  a malignant lesion
      such as choroidal melanoma. CASE REPORT: A 9-year-old male patient consulted our
      clinic first  in 1991 because of a reduction in visual acuity due to a tumor of
      the optic nerve head in the left eye. Visual acuity was 1.0 in the right eye and
      0.2 in the left eye. Slit lamp examination and intraocular pressure were regular
      in both eyes. Kinetic perimetry showed a enlarged blind spot besides regular
      isopters. Funduscopy revealed a pigmented, ill-defined  prominence of the optic
      nerve head with a mossy surface. In annual examinations were found a slowly
      progredient reduction in visual acuity up to 0.04 durning the last visit in
      January 2000 as well  as a enlargement of the blind spot due to an increasing
      prominence and pigmentation of the optic nerve head. Because of the clincal
      aspect, the slowly progressive course, the enlargement of the blind spot with
      deterioration of vision and especially the florescein angiography, which revealed
      peripapillary capillary alterations with leakage, we diagnosed a proliferation of
      the juxtapapillary retinal pigment epithelium. CONCLUSION: The proliferation of  
      the juxtapapillary retinal pigment epithelium can be differentiated from other
      pigmented tumors of the optic nerve head by its typical clinical aspect and
      course and especially by using flourescein angiography.

PMID- 12227281
TI  - [Increased lens opacity, retinal pigment epithelium degeneration and spontaneous
      retinal detachment in a family. Wagner syndrome].

PMID- 12227282
TI  - [Subjective refraction assessment. II: Monocular fine adjustment].

PMID- 12227283
TI  - The power of influence.

PMID- 12227284
TI  - The essence of our future--capturing polarity and balance.

PMID- 12227285
TI  - Medical device reprocessing--an alternative.

PMID- 12227286
TI  - Revision total hip arthroplasty.
AB  - Endoscopic visualization and pneumatically-powered ballistic chisels that can be
      used to remove cement and cementless prostheses are recent developmental
      improvements for revision total hip arthroplasty (THA). Use of these new tools
      facilitates the revision procedure, reduces tissue trauma, and may reduce
      surgical time. Understanding the anatomy of the hip joint, pathophysiology that
      leads to the need for joint replacement, and the implant selection process can
      assist perioperative nurses in caring for and teaching patients who require
      revision THA and their family members. This article describes implant choices
      based on the type of bone deformity present and the use of the ballistic
      chiseling system during revision THA. Potential postoperative complications also
      are described.

PMID- 12227288
TI  - Designing and implementing a patient safety program for the OR.
AB  - Surgery has a high potential for adverse outcomes. An error involving a retained
      retractor caused perioperative nurses at the University of Washington Medical
      Center, Seattle, to take another look at their department's patient safety
      practices and risk management procedures. Using another department's successful
      program as a model, the nurses considered the frameworks of risk management,
      quality improvement, and OR culture to develop a new patient safety quality
      improvement program for the OR. This article details the process of designing and
      implementing the program, which has energized staff members, enhanced teamwork,
      and resulted in improved patient outcomes.

PMID- 12227287
TI  - Bioterrorism--are you ready for the silent killer?
AB  - Current biological threats to the United States have generated fear and panic
      among many, but nursing professionals who are educated about bioterrorism and its
      effects can answer questions confidently and calm fears when peers, family
      members, and friends ask about this issue. Perioperative nurses can become
      ambassadors of confidence via their ability to project calm and thus stem the
      tide of panic and fear. This article explains the definition of bioterrorism, its
      history, biological agents and their transmission, treatment options, and what
      nurses can do to facilitate preventive measures and help avert panic.

PMID- 12227289
TI  - Obstructive sleep apnea syndrome in ambulatory surgical patients.
AB  - Obstructive sleep apnea in the ambulatory surgery setting has become a more
      significant concern in recent years because its Identification and recognition
      are a critical part of preoperative patients' risk assessment. The types of
      surgeries that can be performed on an outpatient basis have increased and include
      many specialty procedures that previously were performed on an inpatient basis
      only. Ambulatory surgery has proven to be a cost-effective alternative for
      patients and physicians; however, patients in this setting often have complex
      surgical histories. Perioperative nurses must provide a more integrated approach
      to patient assessment to recognize, identify, plan, and implement a course of
      safe care for patients with obstructive sleep apnea. Reviewing patients'
      histories can help nurses identify symptoms of obstructive sleep apnea, allowing
      them to alert the surgical team of special requirements. Ambulatory patients with
      identified obstructive sleep apnea will require a planned course of care.
      Ambulatory care facilities should have a policy in place to ensure that safe care
      will be provided to patients for the entire perioperative course.

PMID- 12227290
TI  - Monitoring bladder temperatures in the OR.
AB  - Temperature monitoring via the urinary bladder has become common in the OR, often
      replacing monitoring at the rectal site. A systematic, integrated review and
      synthesis of the literature was undertaken to assess the validity of using the
      urinary bladder as a site for temperature measurement in the OR. During steady
      thermal states, bladder temperature performed well, providing temperatures
      similar to those of core sites. In contrast, poor performance was demonstrated
      during rapid thermal changes, such as during the rapid cooling and rewarming
      phases of cardiopulmonary bypass. At such times, a significant lag in response
      rate at the bladder site was noted by multiple investigators. This delayed
      responsiveness during thermally dynamic states, however, may provide information
      regarding the adequacy of rewarming during bypass at sites intermediate between
      the core and periphery. Limited research indicates that urinary bladder
      temperature may be influenced by urine flow rate, and additional research is
      required in this area. The cost effectiveness of this method of temperature
      measurement requires investigation as well.

PMID- 12227291
TI  - Ethics in perioperative practice--duty to foster an ethical environment.
AB  - Though often difficult, ethical decision making is necessary when caring for
      surgical patients. Perioperative nurses have to recognize ethical dilemmas and be
      prepared to take action based on the ethical code outlined in the American Nurses
      Association's (ANA's) Code of Ethics for Nurses with Interpretive Statements. In
      this sixth of a nine-part series that will help perioperative nurses relate the
      ANA code to their own area of practice, the author looks at the sixth statement,
      which emphasizes the nurse's duty to promote a working environment that enhances
      quality patient care and fosters the values and behaviors that form the
      foundation of ethical practice.

PMID- 12227292
TI  - Good grief--dealing with ordinary people experiencing the extraordinary.

PMID- 12227293
TI  - Systems that reduce the potential for patient identification errors.

PMID- 12227294
TI  - Correct site verification and consent--two separate legal issues.

PMID- 12227295
TI  - Current federal legislation on patient safety.

PMID- 12227297
TI  - Population and development in Southeast Asia: a fertility model.

PMID- 12227298
TI  - Emerging infections and the skin. Proceedings of the 49th Montagna Annual
      Symposium on the Biology of Skin. Snowmass, Colorado, USA. August 12-16, 2000.

PMID- 12227299
TI  - Proceedings of the Second International Novo Nordisk Symposium on Diabetes in
      Childhood and Adolescence. Copenhagen, Denmark. May 31-June 2, 2001.

PMID- 12227300
TI  - [Medical treatment of acute diarrhea in children].

PMID- 12227301
TI  - [Ophthalmology history].

PMID- 12227302
TI  - In memoriam: John M. Eisenberg, MD, MBA.

PMID- 12227303
TI  - Liposomes. From models to application. Proceedings and abstracts of the W.
      Mejbaum-Katzenellenbogen's Molecular Biological Seminar. May 26-29, 2002.
      Wroclaw, Poland.

PMID- 12227304
TI  - Proceedings of the International Conference on Life Sciences - 2001. September 22
      26, 2001, Gozd Martuljek, Slovenia.

PMID- 12227305
TI  - Neural control of breathing. Proceedings of a satellite meeting following the
      IUSP Congress. September 1-4, 2001, Christchurch, New Zealand.

PMID- 12227306
TI  - Proceedings of the Sixth International Conference on Molecular and Basic
      Mechanisms of Anesthesia. June 28-30, 2001. Bonn, Germany.

PMID- 12227307
TI  - Papers of the Northeastern Society of Plastic Surgeons annual meeting.
      Philadelphia, Pennsylvania, USA. October 4-6, 2001.

PMID- 12227311
TI  - Young women and labor: in-school labor force status and early postschool labor
      market outcomes.

PMID- 12227315
TI  - Why economic-demographic models have not been used in the Philippines.

PMID- 12227316
TI  - Optimal city size and population density for the 21st century.

PMID- 12227323
TI  - Current status of research and development of vaginal contraceptive rings as a
      fertility control method in the female.

PMID- 12227327
TI  - New approaches to vaccine development. Proceedings of a meeting organized by the
      World Health Organization. Book review.

PMID- 12227328
TI  - Childlessness patterns in Taiwan.

PMID- 12227329
TI  - Expression of the endothelial receptor tyrosine kinase Tie2 in lobular capillary
      hemangioma of the oral mucosa: an immunohistochemical study.
AB  - BACKGROUND: Lobular capillary hemangioma (LCH) usually occurs in the skin or
      mucous membranes as a rapidly growing red nodule. LCH is one of the most common
      vascular lesions in the oral mucosa. Tie2 is a novel, human endothelial receptor
      tyrosine kinase which may play an important role in blood vessel formation. In
      this study, we investigated its immunohistochemical expression in LCH of the oral
      mucosa. METHODS: Double immunostaining with anti-CD34 and antialpha smooth muscle
      actin (SMA) antibodies was performed to characterize the cellular expression of
      Tie2 in 15 cases of this condition. RESULTS: We found Tie2 immunoreactivity in
      the ovoid cells only, which were frequently intermingled with alphaSMA-positive
      cells, especially in the hypercellular portion of LCH. CONCLUSIONS: These results
      suggest that the expression of Tie2 in ovoid cells and the interaction between
      ovoid cells and alphaSMA-positive cells play an important part in the development
      and progression of LCH.

PMID- 12227330
TI  - Quadrennial reviews and working party reports from the World Congress in
      Gastroenterology. February 24-March 1, 2002. Bangkok, Thailand.

PMID- 12227332
TI  - Hard lessons from a randomised controlled trial.

PMID- 12227333
TI  - The demise of a planned randomised controlled trial in an urban Aboriginal
      medical service.

PMID- 12227334
TI  - Theoretical considerations regarding the study "Alpha-B crystallin gene (CRYAB)
      mutation causes dominant congenital posterior polar cataract in humans".

PMID- 12227335
TI  - Vascular adaptation to microgravity: extending the hypothesis.

PMID- 12227336
TI  - Current awareness in prenatal diagnosis.

PMID- 12227337
TI  - Nurse recruitment. Going places.
AB  - Overseas nurses account for 40 per cent of all new registrations in the UK and
      this may be rising to 50 per cent. This upward trend is likely to continue.
      International recruitment is to be part of the NHS's long-term strategy and is
      becoming the focus of increasing policy attention. The international labour
      market will become tighter: the US needs to recruit an extra million nurses of
      its own.

PMID- 12227338
TI  - Can reflux prevention prevent esophageal adenocarcinoma?

PMID- 12227339
TI  - Chlororespiration.
AB  - Chlororespiration has been defined as a respiratory electron transport chain
      (ETC) in interaction with the photosynthetic ETC in thylakoid membranes of
      chloroplasts. The existence of chlororespiration has been disputed during the
      last decade, with the initial evidence mainly obtained with intact algal cells
      being possibly explained by redox interactions between chloroplasts and
      mitochondria. The discovery in higher-plant chloroplasts of a plastid-encoded
      NAD(P)H-dehydrogenase (Ndh) complex, homologous to the bacterial complex I, and
      of a nuclear-encoded plastid terminal oxidase (PTOX), homologous to the plant
      mitochondrial alternative oxidase, brought molecular support to the concept of
      chlororespiration. The functionality of these proteins in non-photochemical
      reduction and oxidation of plastoquinones (PQs), respectively, has recently been
      demonstrated. In thylakoids of mature chloroplasts, chlororespiration appears to
      be a relatively minor pathway compared to linear photosynthetic electron flow
      from H2O to NADP+. However, chlororespiration might play a role in the regulation
      of photosynthesis by modulating the activity of cyclic electron flow around
      photosystem I (PS I). In non-photosynthetic plastids, chlororespiratory electron
      carriers are more abundant and may play a significant bioenergetic role.

PMID- 12227340
TI  - Acrophialophora fusispora misidentified as Scedosporium prolificans.

PMID- 12227341
TI  - [Contribution of phenomenological studies to nursing care].
AB  - This essay reflects the contributions of phenomenological studies to nursing
      care, as exemplified in the knowledge concerning the adhesion of persons
      suffering from coronary diseases to daily idle talk. It considers that the
      understanding of human manifestations allows one to interpret attitudes and
      behaviors and that the contributions of phenomenological studies can facilitate
      the reach of excellence in nursing care.

PMID- 12227342
TI  - [Historical retrospective of the Brazilian Nurses Association--The Goias
      chapter].
AB  - The present work presents a brief retrospective of the main facts that were part
      of the creation of the Brazilian Association of Nursing in Goias Federal State.
      It identifies meaningful accomplishments of its administrations from 1948 up to
      2001, pointing out its concerns, struggles and achievements based on documents
      such as book-proceedings, written documents, publications and reports of people
      who were involved with the association. It was concluded that this is an
      appropriate time for proposals which aim at the historical, political and social
      rescue of this association.

PMID- 12227343
TI  - [Newborn birth weight, maternal age group and delivery method].
AB  - This article has as its objective the study of the weight of the newly born, the
      age group of the mother and the kind of deliveries which took place in the
      maternity wards in Rio Branco--Acre Federal State--Brazil, in the period between
      1994 and 1996. It was observed that 73.8% of the deliveries were regular and
      25.5% were cesareans. Adolescents, between 10 to 14 years old represented 5.4% of
      the total of the deliveries. In relation to the weight of the newly born, 84.6%
      met the expectations, 7.4% were underweight and 6.6% were overweight. The present
      study also found that the data related to weight, age and gender was ignored in
      many cases, which shows flaws on the registration system of the institutions
      analyzed. As a conclusion, we would like to stress the importance of prenatal
      assistance both for the mother and the child, and also the effort on the part of
      the Maternity and Nursing management regarding the production and analysis of
      data.

PMID- 12227344
TI  - [Sexually transmitted diseases and HIV/AIDS: Nursing discussion about dangerous
      relations for women].
AB  - The present article has as its main objective the discussion of the risky
      relationship between sexually transmitted diseases (STDs) and the HIV/AIDS under
      the perspective of gender and sexuality. It presents the increase of AIDS among
      women as a consequence of social, political, cultural and economic relations. The
      study uses an exploratory methodology of qualitative nature. It focuses on women
      who are HIV positive and acquired the disease through sexual relationships with a
      stable partner. The study concluded that nursing care is a very important
      opportunity for nurses to make an early diagnosis, treatment and prevention of
      the STDs and AIDS.

PMID- 12227345
TI  - [Pain in the newborn and the infant].
AB  - The present study analyses the representations of nurses, who were either
      students of a Pediatric Health or a Neonatal Nursing specialization courses in
      different universities in the city of Rio de Janeiro. This work was based on the
      theoretical framework of Social Representations. The methods used were dynamics
      of creativity and sensibility, as well as semi-structured interviews. Results
      showed that nurses have a subjective representation of the pain, and that these
      representations are influenced by their own life experiences. It also concluded
      that the nurse's personal experiences interfere in their professional attitudes
      and sensitivity towards the reaction of children and newborns who undergo painful
      treatments.

PMID- 12227346
TI  - [Oral health: a challenge for the health care team].
AB  - The objective of this study is to reveal the knowledge of nursing and medicine
      students from a university in Rio Grande do Sul regarding the importance of
      promoting dental health. A questionnaire with three semi-structured questions was
      answered by 26 students from the nursing school, and by 32 students from the
      medical school. Through the method of triangulation it was concluded that these
      students had deficient knowledge regarding dental health. Since a small number of
      the population in Brazil has access to dental clinics, we consider important that
      nursing and medicine professionals know how to promote dental care among
      children.

PMID- 12227347
TI  - [Graduate nursing education as the locus of the nurse training: curriculum
      guidelines and pedagogic project].

PMID- 12227348
TI  - [About homeopathy. 1930].

PMID- 12227349
TI  - Cautionary notes on interpreting the efficacy of treatment programs for children
      who stutter.

PMID- 12227351
TI  - 2003 HOPPS includes cuts for nuclear medicine.

PMID- 12227352
TI  - A comparison of the effects of broadband masking noise on the auditory brainstem
      response in young and older adults.
AB  - We examined the effects of ipsilateral-direct, continuous, broadband noise on
      auditory brainstem response (ABR) wave I and V latencies and amplitudes in young
      adult versus older adult humans. It was hypothesized that age might influence the
      effects of masking noise on ABR peak latencies and/or amplitudes, given the
      frequent complaint of older persons' ability to process speech in background
      noise. Young adults had hearing thresholds of 20 dB HL or better for the octave
      frequencies from 250 to 8,000 Hz. A subset of older study participants had
      thresholds of 20 dB HL or better across frequency, but others had thresholds up
      to 45 dB HL. All data were collected and analyzed with a Nicolet Bravo. An
      electrode was placed on the tympanic membrane (as well as on high forehead and
      contralateral mastoid), and a click level of 115 dB pSPL was used to maximize
      wave I amplitude. Masker conditions included a no-noise control and noise levels
      ranging from 20 to 70 dB effective masking, in 10 dB steps. With increasing noise
      level, both age groups showed minimal changes in wave I latency, but substantial
      increases in wave V latency and I-V interval. Peak amplitudes decreased with
      increasing noise level. Mean amplitudes were smaller for the older group, most
      notably for wave I. Mean peak latencies were greater in the older group, but the
      I-V interval was similar across age groups, as was the change in peak latencies
      and I-V interval across noise level. ABR parameters for the older adults with
      hearing meeting the 20-dB HL criterion at all frequencies (older-better) were
      compared to those who didn't meet this criterion (older-worse). Mean wave I
      latency was greater and wave V latency and I-V interval were smaller for the
      older-worse group at all noise levels. Mean wave I and V amplitudes were similar
      for the older-better and older-worse groups. In participants with normal or near
      normal hearing, ABR changes with increasing age included small latency increases
      and a substantial reduction in wave I amplitude. The effects of ipsilateral
      direct masking noise on the click-evoked ABR are similar for young and older
      adults.

PMID- 12227353
TI  - Is the tail wagging the dog?

PMID- 12227354
TI  - Digit speech recognition thresholds (SRT) for non-native speakers of English.
AB  - Although Central Institute for the Deaf (CID) W-1 stimuli are routinely used for
      speech recognition threshold (SRT) testing, they are not always familiar to new
      learners of English and often lead to erroneous assessments. To improve test
      accuracy, alternative stimuli were constructed by pairing familiar English
      digits. These digit pairs were used to measure SRT for 12 non-native speakers of
      English and 12 native speakers of English. Results indicate that digit pairs
      effectively measure SRT for both participant groups; and more importantly, for
      non-native speakers of English, digit pairs are more accurate than CID W-1 words
      in measuring the hearing threshold for speech. Digit-pairs have cross-linguistic
      appeal and should greatly facilitate accurate SRT testing for listeners with
      minimal exposure to English.

PMID- 12227355
TI  - Low-frequency gain compensation in directional hearing aids.
AB  - Hearing aids currently available on the market with both omnidirectional and
      directional microphone modes often have reduced amplification in the low
      frequencies when in directional microphone mode due to better phase matching. The
      effects of this low-frequency gain reduction for individuals with hearing loss in
      the low frequencies was of primary interest. Changes in sound quality for quiet
      listening environments following gain compensation in the low frequencies was of
      secondary interest. Thirty participants were fit with bilateral in-the-ear
      hearing aids, which were programmed in three ways while in directional microphone
      mode: no-gain compensation, adaptive-gain compensation, and full-gain
      compensation. All participants were tested with speech in noise tasks.
      Participants also made sound quality judgments based on monaural recordings made
      from the hearing aid. Results support a need for gain compensation for
      individuals with low-frequency hearing loss of greater than 40 dB HL.

PMID- 12227356
TI  - Educating audiologists: diversity or homogeneity?

PMID- 12227357
TI  - An electrophysiological measure of temporal resolution in normal subjects using
      frequency modulated signals.
AB  - This investigation was conducted to determine whether an exogenous event-related
      potential called the mismatch negativity (MMN) would change systematically in
      response to frequency-modulated signals with varying temporal properties. Both N1
      and P2 waveforms were recorded for 50-ms frequency-modulated signals from normal
      hearing listeners. The standard stimuli for this investigation were continuous
      sweep tones with center frequencies of 1000 Hz that traversed a frequency range
      of 200 Hz in a single step. The rare stimuli were signals that traversed the same
      frequency range in two, four, six, or eight discrete steps. Results suggest that
      for the 10 participants, 1) the mean MMN peak-to-peak amplitude and mean area
      decreased significantly with decreases in step duration, 2) MMN area amplitude
      was the best indicator of psychophysical performance for the two magnitude
      measures, and 3) MMN onsets and peak latencies did not show either a significant
      increase or decrease in latency as step duration decreased.

PMID- 12227358
TI  - Factor analysis in CAPD and the "unimodal" test battery: do we have a model that
      will satisfy?

PMID- 12227359
TI  - Microcalcification in a core or needle localized biopsy in which it is the
      radiologic target are a "totally inconsequential and inappropriate function" for
      a pathologist.

PMID- 12227360
TI  - Erectile dysfunction and symptoms of sleep disorders.
AB  - STUDY OBJECTIVES: Sleep apnea often is associated with impotence and/or erectile
      dysfunction (ED). The purpose of this study was to test whether a presentation
      for ED confers a pretest probability for obstructive sleep apnea hypopnea
      syndrome (OSAHS). DESIGN: A self-report survey for sleep complaints was conducted
      in consecutive male patients (>16 years of age) presenting to a urologic practice
      site. SETTING: The survey was provided to new and follow-up out-patients over a 2
      month period of time. Other information collected included the presenting
      complaint, the clinical diagnosis for ED, and history of preexisting medical
      conditions. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: 285
      males [91% of the sample: 50 years old (range 16-82) and body mass index, 27.3
      (range 16.8-52.5)] completed the survey. 181 (63%) had complaints of ED; of
      those, 76% had a final diagnosis of organic and 8.2%, psychogenic or both
      psychogenic and organic ED. Of all respondents, 35.4% reported persistent
      snoring, 14% reported persistent waketime sleepiness or fatigue, and 26.8% were
      at "high risk" (Netzer et al., 1999) for OSAHS. Some were high risk for insomnia
      (13.6%) and restless legs syndrome or for narcolepsy (2% each). There was a
      correlation between those with ED complaints (p<0.014) or those with a final
      diagnosis of organic ED (p<0.029) and snoring. In a logistic model that included
      age, snoring, and preexisting conditions, only age, depression, and history of
      hypercholesterolemia, were found to vary significantly among those with and
      without ED. CONCLUSIONS: Urology patients will report a variety of sleep
      problems, but neither persistent snoring nor suspected OSAHS is correlated
      uniquely to ED.

PMID- 12227361
TI  - The Portsmouth Voluntary Hospitals Database: using PERL to achieve automatic
      linkage of scanned text files to an existing database.

PMID- 12227362
TI  - Medical films, ethics and euthanasia in Nazi Germany: the history of medical
      research and teaching films of the Reich Office for Educational Films, Reich
      Institute for Films in Science and Education, 1933-1945.

PMID- 12227363
TI  - [Werner Villinger (1887-1961): the continuity of the concept of inferiority in
      youth and social psychiatry].

PMID- 12227364
TI  - [The search for reform of medical education in nineteenth-century Spain].

PMID- 12227365
TI  - Pulmonary dead space and survival.

PMID- 12227366
TI  - Pulmonary dead space and survival.

PMID- 12227367
TI  - Pulmonary dead space and survival.

PMID- 12227368
TI  - Pulmonary dead space and survival.

PMID- 12227369
TI  - Neuroblastoma screening in early life.

PMID- 12227370
TI  - Neuroblastoma screening in early life.

PMID- 12227371
TI  - Neuroblastoma screening in early life.

PMID- 12227372
TI  - Case 9-2002: orbital mucormycosis.

PMID- 12227373
TI  - Case 9-2002: orbital mucormycosis.

PMID- 12227374
TI  - An experimental study and mathematical simulation of adrenergic control of
      hindlimb vessels in rats after 3-week tail suspension.
AB  - Adrenoreactivity of rat hindlimb vessels was studied in experiments with constant
      pressure saline perfusion. An original mathematical model was applied to evaluate
      the mechanism of changes in vascular tone regulation. A 3-week suspension
      resulted in decreased responses to sympathetic nerve stimulation, as well as to
      exogenous noradrenaline, the latter effect being registered when the pressure
      level was close to normal. Mathematical simulation indicated that long-term
      suspension induces both structural and functional changes in the vascular bed of
      the hind limbs, one of which is a disorder in the myogenic mechanisms of vascular
      tone regulation. In suspended rats, suppression of the myogenic response can be
      one of the reasons for decreased vessel reactivity to constrictor stimuli and,
      consequently, for disturbances in blood flow regulation in skeletal muscles of
      the hind limbs.

PMID- 12227375
TI  - Culture in vector-averaged gravity environment in a clinostat results in
      detachment of osteoblastic ROS 17/2.8 cells.
AB  - Studies carried out in space flights and in altered gravitational environments
      have shown that exposure to altered gravity conditions results in alterations in
      cellular structure and function. In the present study, we used a clinostat to
      generate a vector-averaged gravity environment, and evaluated the responses of
      osteoblast-like ROS 17/2.8 cells subsequent to rotation at 50 r.p.m from 24 to 72
      hr. We found that the cells started to detach during the first 24 hr of culture
      in clinostat, but not in stationary and horizontal rotation (the latter serving
      as a control for turbulence, shear forces and vibrations). At 24 hr, there was a
      significant decrease in the number of adherent cells under clino-rotation (2.75
      +/- 0.5 x 10(5) in stationary culture versus 2.02 +/- 0.27 x 10(5) under clino
      rotation), and 19.8% of adherent cells were trypan-blue positive when cultured in
      2% fetal bovine serum. All the detached cells were trypan-blue positive. At 72
      hr, the cells became confluent in all three groups. These results suggest that
      vector-averaged gravity could cause the death of osteoblasts during the first 24
      hr of clino-rotation. We hypothesize that this cell death might play a role in
      the pathogenesis of osteoporotic bone loss as observed in actual space flight.

PMID- 12227376
TI  - Effects of vector-averaged gravity on NF-kappa B activation in human osteoblast
      like cells.
AB  - We have recently demonstrated that a transcription factor, nuclear factor kappa B
      (NF-kappa B), plays a key role in the production of cytokine and cell adhesion
      molecules in osteoblastic cells. In the present study, we investigated the
      effects of vector-averaged gravity (clinostat rotation) on tumor necrosis factor
      (TNF)-alpha-induced activation of NF-kappa B in human osteoblastic HOS-TE85
      cells. After a 72-hr clinostat culture, the cells were treated with TNF-alpha for
      30 min. Electrophoretic mobility shift assay using the nuclear extracts revealed
      that the DNA-binding activity of NF-kappa B was substantially reduced in
      clinostat-cultured cells compared with the stationary control. Concomitantly, the
      transactivation of NF-kappa B was examined by a transfection study. The cells
      were transfected with a plasmid expressing a luciferase reporter gene driven by
      multimerized NF-kappa B sites. They were cultured in the clinostat for 48-hr,
      followed by a 4-hr treatment with TNF-alpha. Clinostat culture resulted in a
      significant decrease in the luciferase activities, being consistent with the
      decreased binding of NF-kappa B. These results indicate that exposure of HOS-TE85
      cells to vector-averaged gravity impairs NF-kappa B activation by TNF-alpha.

PMID- 12227377
TI  - A comparison of effects between accelerated heavy ion irradiation and X
      irradiation on the development of rat cerebellum.
AB  - The purpose of this experiment is to compare the effects of 290 MeV/u carbon-ion
      irradiation and X-irradiation on the development of rat cerebellum. Pregnant rats
      were exposed to carbon-ion beams at a single dose of 1.5 Gy on day 19.0 of
      gestation. Other groups of pregnant rats were exposed to X-rays on day 19.0 at
      single doses of 1.5, 2.0 and 2.5 Gy. Their fetuses were removed 8 hr after
      exposure, and an acute effect examined microscopically for cell death in the
      external granular layer of the cerebellum. Other dams were allowed to give birth
      and rear their litters. The offspring were sacrificed at 6 weeks of age, and
      their cerebella were examined for foliar malformation. The results showed that
      the effect of 1.5 Gy carbon-ion irradiation on the development of cerebellum was
      stronger than that of 1.5 Gy X-irradiation and similar to 2.0-2.5 Gy X
      irradiation.

PMID- 12227378
TI  - Influence of postural changes on nystagmic elicitation induced by linear
      acceleration.
AB  - Functional nystagmic eye movements are compensatory responses meant to stabilize
      the gaze during head movement. Niven et al. (1966) have reported that otolithic
      nystagmus can be elicited by linear acceleration in humans only along interaural
      (Y-axis) acceleration (Gy), but not along occipitonasal (X-axis) or head-to-foot
      (Z-axis) acceleration. This result was reexamined in the present study in normal
      subjects who elicited lateral (Gy) nystagmus frequently. The nystagmic
      elicitation was examined by EOG in 4 healthy subjects who were fastened tightly
      in the chair of a linear accelerator and instructed to look straight ahead at an
      imaginary target in the dark. The stimulation was five oscillations of a constant
      10-m stroke at two different acceleration levels of 0.3 and 0.5 G in a step mode.
      The X- and Z-axis accelerations did not induce any horizontal or vertical
      nystagmus, while the Y-axis acceleration did, in agreement with the above report.
      However, it was found that nystagmic elicitation due to Gy loading tended to be
      lower in the supine than in the upright sitting position. The present finding
      that nystagmic slow-phase velocity (SPV) increased with an increase in the G-load
      also contradicted the above report. Upright subjects who showed G-directional
      preponderance (DP) in nystagmic elicitation did not always maintain DP when
      supine. No relation could be seen between DP and SPV, suggesting that DP might be
      generated by a central mechanism different from SPV control.

PMID- 12227379
TI  - Toothpaste:  only recently has it started doing more good than harm.

PMID- 12227380
TI  - Paracelsus, Paracelsianism, and the secularization of the worldview.
AB  - This paper examines Paracelsus and Paracelsianism in the light of the ideas of
      Max Weber concerning the social consequences of the Reformation, with special
      reference to his theories of Entzauberung and secularization. He linked these
      tendencies both to the rise of capitalism and the growth of experimental science.
      The detailed case study of Paracelsus' account of diseases linked with saints, in
      common with his interpretation of many other conditions, demonstrates that he
      self-consciously extended the boundaries of medicine and eroded the role of magic
      and witchcraft associated with the church. On the other hand, Paracelsus adopted
      the Neoplatonic worldview, was immersed in popular magic, and evolved a system of
      medicine that self-consciously revolved around magic. These factors seem to place
      a distinct limit on his role in the demystification of knowledge. However, the
      magic of Paracelsus entailed a decisive break with the entrenched elitist and
      esoteric tradition of the occultists and hermeticists. It is argued that this
      reconstructed magic re-establishes the credentials of Paracelsus as a significant
      contributor to the disenchantment and secularization of the worldview.

PMID- 12227381
TI  - [Johann Peter Philipp Poppert (1860 - 1933): advocate of surgery in Giessen from
      1900 to 1933].

PMID- 12227382
TI  - Revisiting the relationships among gender, marital status, and mental health.
AB  - Three decades ago, Grove introduced his sex-role theory of mental illness, which
      attributes women's higher rates of psychological distress to their roles in
      society. Central to his hypothesis is that marriage is emotionally advantageous
      for men and disadvantageous for women. This article revisits this topic with data
      from the National Survey of Families and Households. The analyses indicate that
      the emotional benefits of marriage apply equally to men and women, but that men
      and women respond to marital transitions with different types of emotional
      problems. The implications of these findings for future research on gender and
      mental health are discussed.

PMID- 12227383
TI  - Effects of bisphosphonate on bone metabolism in tail-suspended rats.
AB  - Our previous studies demonstrated that tail suspension causes early, transient
      increases in osteoclastic activity, followed by a decrease in osteoblastic
      activity in the hind limbs of rats. To assess whether this early increase in bone
      resorption is important in the development of disuse atrophy, the effect of
      YH529, a third generation bisphosphonate, was studied on hind limb atrophy in
      rats subjected to tail suspension. YH529 (YH group) or PBS (control group) were
      administered subcutaneously in 5-week-old male Wistar rats suspended for 7 days.
      In the control group, wet weight, calcium and phosphorus contents decreased
      significantly in the femur but they did not change in the humerus. In the YH
      group, however, these parameters did not change significantly in the femur, but
      both calcium and phosphorus increased significantly in the humerus. These results
      indicate that the inhibition of bone resorption by YH529 prevents the development
      of disuse atrophy induced by tail suspension. It is thus suggested that early
      increases in bone resorption are important for the development of disuse bone
      atrophy.

PMID- 12227384
TI  - Changes in serum concentrations of calcium and its regulating hormones during
      tail suspension in rats.
AB  - To study the effects of mechanical unloading on systemic calcium homeostasis, we
      determined the changes in serum concentration of calcium, 1,25-dihydroxyvitamin
      D3 and parathyroid hormone (PTH) during tail-suspension experiments in rats. The
      serum concentration of ionized calcium significantly increased during the 14 days
      of the suspension, reflecting increased bone resorption in the hind limbs. This
      hypercalcemic condition should cause suppression in PTH secretion. Indeed, serum
      PTH levels decreased on Day 3 of the suspension. This decrease was associated
      with lower serum levels of 1,25-dihydroxyvitamin [correction of dihyroxyvitamin]
      D3 probably due to a decrease in the activity of 1 alpha-hydroxylase in the
      kidneys resulting from a decrease in PTH secretion. Since it is known that 1,25
      dihydroxyvitamin D3 stimulates osteoblastic function, it is suggested that
      endocrine responses evoked by tail suspension aggravate disuse atrophy of the
      hind limbs.

PMID- 12227385
TI  - L-2-oxothiazolidine-4-carboxylate: an agent that modulates lipopolysaccharide
      induced peritonitis in rats.
AB  - OBJECTIVE: L-2-Oxothiazolidine-4-carboxylate (OTZ), a cysteine precursor, is a
      substrate for intracellular glutathione synthesis. As shown previously, OTZ
      prevents free-radical induced cellular damage during in vitro simulation of
      peritoneal dialysis. In the present study, we examined the effect of adding OTZ
      to peritoneal dialysis solution on peritoneal function and structure during
      lipopolysaccharide (LPS)-induced peritonitis in rats. In addition, we studied the
      effects of pretreatment with OTZ (given orally) on the effects of LPS-induced
      peritonitis in rats. METHODS: Peritonitis was induced in rats by adding LPS (5
      microg/mL) to the dialysis fluid. For acute experiments, rats were exposed to a
      single infusion of dialysis solution containing LPS or to LPS plus 5 mmol/L OTZ;
      peritoneal cell counts and permeability were determined after 4 hours.
      Alternatively, rats were pretreated with OTZ added to the drinking water (0.1%)
      for 10 days prior to infusion of LPS. For chronic experiments, peritoneal
      dialysis was performed over a 3-week period in rats with implanted peritoneal
      catheters. On days 8, 9, and 10 of the experiment, the rats were infused
      intraperitoneally with solution containing LPS (5 micro/mL), or LPS plus 5 mmol/L
      OTZ, to induce acute peritonitis. At the end of dialysis (10 days after the
      episodes of peritonitis), peritoneal function was assessed using a peritoneal
      equilibration test (PET), and peritoneal biopsies were taken to assess effects on
      peritoneal morphology. RESULTS: In the acute experiments, exposure to LPS led to
      increased peritoneal cell counts (+61% vs control, p < 0.05) and enhanced
      permeability of the peritoneum, leading to a loss in ultrafiltration (-63%, p <
      0.0005). The glutathione concentration in peritoneal leukocytes also decreased
      during acute peritonitis (-31%, p < 0.05). During LPS-induced peritonitis, OTZ
      prevented the increase in dialysate cell count and the decrease in cellular
      glutathione content. Simultaneous administration of OTZ did not prevent the
      increased peritoneal permeability induced by LPS. However, in rats pretreated
      with OTZ, LPS-induced permeability to protein was significantly lower than in the
      nontreated animals (0.049 +/- 0.011 vs 0.087 +/- 0.034, p < 0.05). In the chronic
      experiments, LPS-induced peritonitis did not lead to any functional differences
      in peritoneal transport at the end of 3 weeks of dialysis. However, LPS-induced
      peritonitis led to increased thickness of the peritoneum and neovascularization
      within peritoneal interstitium compared to peritonitis-free animals. In contrast
      to the LPS-treated animals, the peritoneum of the rats exposed to LPS in the
      presence of OTZ was of a thickness similar to that in the control rats.
      CONCLUSION: Supplementation of dialysis fluid with OTZ prevented changes in
      cellular glutathione levels and dialysate cell counts during acute peritonitis in
      rats. During chronic dialysis in rats exposed to intermittent peritonitis
      episodes, OTZ prevented increased thickening and neovascularization of the
      peritoneum. Our results suggest this may help to protect the peritoneal membrane
      during episodes of peritonitis.

PMID- 12227386
TI  - By reducing production of vascular endothelial growth factor octreotide improves
      the peritoneal vascular alterations induced by hypertonic peritoneal dialysis
      solution.
AB  - OBJECTIVE: Chronic peritoneal dialysis (PD) may eventually result in vascular
      alterations of varying degree, which lead to progressive reduction in dialytic
      efficacy. Although the pathogenesis has not been elucidated yet, vascular
      endothelial growth factor (VEGF) has been proposed to play a central role in the
      process leading to vascular alterations. DESIGN: Rats were allocated to three
      groups: no treatment, intraperitoneal introduction of hypertonic PD solution
      alone, and intraperitoneal introduction of hypertonic PD solution plus
      octreotide. After 4 weeks, a 1-hour peritoneal equilibration test (PET) was
      performed. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0
      glucose), ultrafiltration volume (UF), and levels of dialysate protein and VEGF
      were determined. Peritoneal membrane histology was evaluated by light microscopy.
      RESULTS: Compared with the control group, rats treated with hypertonic PD
      solution showed dramatically deranged peritoneal function tests (UF: 5.8 +/- 0.9
      mL vs 1.3 +/- 0.6 mL; D/P urea: 0.49 +/- 0.1 vs 0.74 +/- 0.04; D1/D0 glucose:
      0.55 +/- 0.05 vs 0.34 +/- 0.06) and morphology (thickness: 4.6 +/- 0.4 mu vs 62
      +/- 12 mu; neovascularisation: 0.1 +/- 0.3 vessels per field vs 2.2 +/- 0.3
      vessels per field). Similarly, a higher level of VEGF was found in the rats
      treated with hypertonic PD solution. In rats treated with hypertonic solution
      plus octreotide, peritoneal thickness was not completely reduced (25 +/- 5 mu),
      but peritoneal functions were protected (UF: 4.0 +/- 0.5 mL; D/P urea: 0.58 +/-
      0.02; D1/D0 glucose: 0.51 +/- 0.02). Moreover, VEGF level and neoangiogenesis
      were significantly less in the octreotide group than in the group treated with
      hypertonic dextrose alone. CONCLUSION: Our data document that, by increasing the
      production of VEGF, a high glucose concentration can cause vascular alterations
      within the peritoneal membrane. Octreotide can protect against the vascular
      alterations and preserve peritoneal function by inhibiting overexpression of VEGF
      and regulating the inflammatory response in the peritoneum.

PMID- 12227387
TI  - Expression of aquaporin-1 in the peritoneal tissues: localization and regulation
      by hyperosmolality.
AB  - OBJECTIVE: The purpose of this study was to determine the localization of the
      aquaporin-1 (AQP1) water channel in peritoneal tissues and the effect of
      hyperosmolality on the peritoneal expression and function of AQP1. METHODS:
      Immunohistochemical localization of AQP1 was identified in rat peritoneal
      tissues. Cultured rat peritoneal mesothelial cells (RPMCs) were exposed to
      hyperosmolality by adding 4% glucose to the culture medium. After 1 hour, 4
      hours, 24 hours, and 48 hours, AQP1 was identified by semiquantitative immunoblot
      and immunocytochemistry. Osmotic water permeability was measured using a light
      scattering method. RESULTS: Immunohistochemistry of rat peritoneal tissues showed
      the presence of AQP1 in mesothelial cells, venular endothelial cells, and
      capillary endothelial cells, but not in arteriole and interstitial cells.
      Semiquantitative immunoblot revealed that exposure to hyperosmolality
      significantly increased AQP1 expression after 24 hours in whole RPMC lysates (3.3
      fold at 24 hours and 3.9-fold at 48 hours). Consistent with the immunoblot,
      osmotic water permeability of RPMC was augmented 1.7-fold and 2.7-fold after 1
      hour and 24 hours, respectively, in a hyperosmotic environment. In RPMC membrane
      fractions, AQP1 expression was significantly increased after 1 hour of exposure
      to hyperosmolality (3.9-fold at 1 hour, 7.1-fold at 4 hours, and 8.7-fold at 24
      hours). Immunocytochemistry of RPMCs showed that AQP1 was gradually redistributed
      from the perinuclear area to the peripheral cytoplasm, and then to the plasma
      membrane after a 1-hour hyperosmotic challenge, suggesting hyperosmolality
      induced translocation of AQP1. Upregulation of AQP1 was also observed in the
      omentum of rats loaded intraperitoneally with hyperosmotic dialysate every day
      for 10 weeks. CONCLUSION: AQP1 is widely distributed in the peritoneal cavity and
      may provide the major aqueous pathway across the peritoneal barrier. In addition,
      our findings suggested that hyperosmolality increases AQP1-dependent water
      permeability in peritoneal tissues by regulatIng the translocation and synthesis
      of AQP1 protein.

PMID- 12227388
TI  - Comparison of the radioiodinated serum albumin (RISA) dilution technique with
      direct volumetric measurements in animal models of peritoneal dialysis.
AB  - BACKGROUND: Rat models of peritoneal dialysis (PD) are useful for studying the
      physiology of peritoneal transport and evaluating new osmotic agents.
      Intraperitoneal (IP) solute concentrations and their evolution over time are easy
      to measure, but IP volume (IPV) is not. Direct volumetric measurements are the
      "gold standard:" but they are expensive and do not allow for repetitive
      measurements in the same animal. The Indicator dilution technique is therefore
      used as an alternative. However, that technique is based on assumptions that are
      not always valid. The present study compares direct volume measurement with the
      Indicator dilution technique [radioiodinated serum albumin (RISA)] to determine
      the IPV over time curves In a rat model of PD. METHODS: In series 1, 17 Sprague
      Dawley rats were instilled IP with 25 mL 1.36% glucose dialysate through a Teflon
      catheter. In 9 animals, 0.35 mL dialysate was sampled and discarded at time
      points 0, 3,15, 30, 60, 180, and 240 minutes. In the other 8 animals, no sampling
      was performed. At 240 minutes, all 12 animals were humanely killed, and direct
      volumetric measurements of IPV were performed. In series 2, rats were instilled
      IP with 25 mL 1.36% glucose dialysate containing 18.5 kBq 1311 RISA. In 9
      animals, dialysate was sampled at 0, 3, 15, 30, 60, 90, 120,180, and 240 minutes
      for the construction of the RISA concentration-over-time curve, and to calculate
      the elimination constant Ke. At 30, 60, 180, and 240 minutes, dialysate was
      sampled in 6 different animals (total n = 24) to calculate IPV using the RISA
      dilution technique. Immediately afterward, the animals were humanely killed, and
      direct volumetric measurements of IPV were performed. RESULTS: In series 1, after
      240 minutes' dwell time, the IPV was lower in the sampled animals as compared
      with the non sampled animals (27.11 +/- 1.85 mL vs 30.75 +/- 0.59 mL, p = 0.001).
      In series 2, the evolution of RISA activity in the dialysate over time was
      described by piecewise linear regression, yielding 3,288--8.2T counts (cts) for T
      < 52.72 minutes and 2,973--1.99T counts for T > 52.72 minutes. The IPV was better
      predicted with a Ke that took into account the disappearance of RISA by sampling
      than with a Ke that took into account disappearance of RISA only by absorption.
      CONCLUSIONS: If indicator dilution techniques are used to measure IPV, attention
      must be paid to the disappearance of the osmotic agent and the marker by multiple
      sampling. The best way to meet that goal is to use micropipettes to avoid large
      sample volumes.

PMID- 12227389
TI  - Abdominal catastrophe revisited: the risk and outcome of enteric peritoneal
      contamination.
AB  - OBJECTIVE: Peritonitis from a visceral source is associated with striking
      morbidity and mortality in patients treated with peritoneal dialysis (PD).
      Surgical intervention for both diagnosis and repair is definitive. However,
      because the antecedents of enteric injury leading to peritonitis are
      unpredictable, no preventive strategy has been proposed or adopted. The goal of
      this study was to examine risk factors influencing the occurrence and outcome of
      anatomically documented peritonitis of enteric origin. DESIGN: Retrospective
      chart and database review. SETTING: Peritoneal dialysis unit in tertiary-care
      referral hospital. PATIENTS: 330 patients treated with PD for end-stage renal
      disease between 1988 and 2000. MAIN OUTCOME MEASURES: Prevalence of peritonitis
      of anatomically documented enteric origin over two consecutive time periods
      within the study interval: period 1, from 1 January 1988 through 30 June 1996;
      period 2, from 1 July 1996 through 30 June 2000. RESULTS: At least 1 episode of
      peritonitis occurred in 202 of 330 patients during the entire study period of
      12.5 years (600.74 patient-years of care). There were 543 episodes of
      peritonitis. Anatomically documented visceral Injury caused bacterial peritonitis
      in 41 patients with a total of 63 discrete episodes, an incidence rate of 0.1048
      per patient-year. Peritonitis-free survival was compared between the two periods
      using Kaplan-Meier analysis. The curve representing risk distribution for
      anatomically documented visceral peritonitis remained constant over the two
      periods, in contrast to improvements found in all other types of peritonitis,
      taken as a group (p= 0.044). Logistic regression modeling showed that the only
      risk factor associated with development of anatomically documented visceral
      peritonitis was older age. There was no influence of race, sex, time on PD, and
      underlying disease etiology. 31 deaths were attributed to peritonitis during the
      study period. The mortality rate from enteric peritonitis due to visceral injury
      was 46.3% (19/41 cases), compared to 7.5% for all other peritonitis taken as a
      group (12/161 cases, p < 0.0001). CONCLUSIONS: The experience at University
      Hospitals of Cleveland suggests that abdominal catastrophe occurs in
      approximately 10% of all patients treated with PD, and is associated with high
      mortality, which has not changed over time. Therefore, peritonitis due to
      spontaneous visceral injury presents a great diagnostic and therapeutic
      challenge. It is important to develop a research strategy to understand this
      devastating complication.

PMID- 12227390
TI  - Challenging the current treatment paradigm for methicillin-resistant
      Staphylococcus epidermidis peritonitis in peritoneal dialysis patients.
AB  - OBJECTIVES: To analyze clinical outcomes of Staphylococcus epidermidis peritoneal
      dialysis peritonitis before and after an interventional switch from a vancomycin/
      tobramycin to a cefazolin/tobramycin regimen for empiric treatment. To examine
      risk factors associated with clinical failure. DESIGN: A retrospective study.
      SETTING: A peritoneal dialysis program within a university-affiliated tertiary
      care hospital. PATIENTS: 93 episodes of S. epidermidis peritonitis over a 6-year
      period. INTERVENTIONS: Clinical responses were compared between treatments using
      chi-square or Fisher's exact test. Univariate and multivariate analyses were used
      to identify significant risk factors for clinical failure. MEASUREMENTS AND MAIN
      RESULTS: There was no difference in the overall response rates observed with
      vancomycin (40/49; 81.6%) and cefazolin (23/29; 79.3%) regimens for episodes of
      S. epidermidis peritonitis. Furthermore, the presence of methicillin resistance
      in 63 of 93 cases (67.7%) had no influence on clinical outcome, with response
      rates of 83.9% (26/31) and 82.4% (14/17) for empiric vancomycin and cefazolin
      regimens, respectively. Tobramycin therapy of less than 2 days was an independent
      risk factor for clinical failure in multivariate logistic regression analysis
      (odds ratio 4.44, 95% confidence interval 1.28 - 15.48; p = 0.02). CONCLUSIONS:
      Empiric treatment with intraperitoneal cefazolin was as effective as vancomycin
      for S. epiderimidis peritonitis despite a high prevalence of methicillin
      resistance. Tobramycin therapy of less than 2 days was strongly associated with
      treatment failure.

PMID- 12227391
TI  - Comparison of vancomycin versus cefazolin as initial therapy for peritonitis in
      peritoneal dialysis patients.
AB  - The incidence of peritonitis ranges from 1 episode every 24 patient treatment
      months to 1 episode every 60 patient treatment months [Keane WF, et al. ISPD
      Guidelines/Recommendations. Adult peritoneal dialysis-related peritonitis
      treatment recommendations: 2000 update. Perit Dial Int 2000; 20:396-411.]. Gram
      positive organisms account for over 80% of continuous ambulatory peritoneal
      dialysis (PD)-associated peritonitis. Recent fear of vancomycin-resistant
      enterococci (VRE) has prompted suggestions of limiting vancomycin use. Fifty-one
      episodes of peritonitis in 30 patients studied over 2 years were evaluated.
      Cloudiness of the PD fluid and/or abdominal pain were considered suggestive of
      peritonitis and were confirmed by cell count and culture. Baseline cell count,
      Gram stain, and cultures were obtained, with periodic follow-up. Patients were
      randomized to receive either vancomycin 1 g/L intraperitoneally (IP) as loading
      dose, repeated on day 5 or day 8, depending on residual renal function, for 2
      weeks, or cefazolin 1 g in the first PD bag and continued with 125 mg/L every
      exchange for 2 or 3 weeks, depending on culture results. All patients also
      received gentamicin 40 mg IP every day until the culture results were available.
      A similar randomized trial comparing vancomycin and cefazolin in the past used a
      lower concentration of cefazolin 50 mg/L [Flanigan MJ, Lim VS. Initial treatment
      of dialysis associated peritonitis: a controlled trial of vancomycin versus
      cefazolin. Perit Dial /nt 1991; 11:31-7.]. Peritoneal dialysate fluid cultures
      revealed 31(60.7%) gram-positive organisms, 7(13.7%) gram-negative organisms, and
      2 (3.9%) cultured yeast; 11 (21.5%) cultures yielded no growth. The incidence of
      peritonitis at our center was 1 episode every 42 patient treatment months. No
      case of VRE was noted. There was no statistical difference in clinical response
      or relapse rate for the two protocols. It was the authors' and nurses'
      observation that patient compliance and satisfaction was better with vancomycin,
      and the cost per treatment was 23% less than cefazolin. Based on these data we
      believe vancomycin should still be considered for first-line treatment of PD
      associated peritonitis.

PMID- 12227392
TI  - Treatment and outcome of peritonitis in automated peritoneal dialysis, using a
      once-daily cefazolin-based regimen.
AB  - OBJECTIVE: We determined the effectiveness of a once-daily cefazolin-based
      regimen in treating automated peritoneal dialysis (APD) peritonitis. DESIGN: We
      carried out a retrospective analysis of all APD peritonitis episodes treated with
      a once-daily cefazolin protocol. SETTING: The study was performed in a peritoneal
      dialysis unit in a tertiary care hospital. PATIENTS AND METHODS: We studied 60
      episodes of primary peritonitis in 40 patients on APD. Each patient was treated
      with a vancomycin-free regimen consisting of intraperitoneal cefazolin (1.5 g IP)
      with gentamicin IP administered in the daytime exchange. The main outcome
      measures were successful treatment of peritonitis, removal of peritoneal
      catheter, relapse of peritonitis, and patient death. RESULTS: Gram-positive
      infections occurred in 35 episodes (58.3%), gram-negative Infections in 10
      episodes (16.7%), culture-negative infections in 14 episodes (23.3%), and a yeast
      infection in 1 episode (1.7%). Of the 60 episodes, 47 (78.3%) were successfully
      treated. In 10 episodes (16.7%), catheters were removed (9 for treatment failure,
      1 for yeast infection). Four patients (8%) had a relapse of infection within 4
      weeks of completing antibiotic therapy. One patient (1.7%) died. CONCLUSIONS: Our
      results demonstrate that once-daily cefazolin with gentamicin IP is an effective
      treatment for APD peritonitis, with the advantage of being easy to administer and
      enabling patients to remain on APD during treatment.

PMID- 12227393
TI  - How to reduce 3-deoxyglucosone and acetaldehyde in peritoneal dialysis fluids.
AB  - OBJECTIVE: 3-Deoxyglucosone (3-DG) and acetaldehyde were found to be the major
      reactive carbonyl compounds in conventional heat-sterilized peritoneal dialysis
      fluids (PDFs). The aim of this study was to identify factors in the production of
      PDFs promoting or inhibiting the formation of acetaldehyde and 3-DG. DESIGN:
      Single-chamber bag PDFs with different buffer systems and pH values were analyzed
      for acetaldehyde. 3-Deoxyglucosone was determined in double-chamber bag PDFs with
      different pH values, in commercially available samples, and in double-chamber
      products stored under defined conditions. RESULTS: Acetaldehyde was found in the
      presence of lactate and malate, whereas in 2-hydroxybutanoate-buffered solution
      propionaldehyde was detected instead. Between pH 5.0 and 6.0 the acetaldehyde
      content in lactate-buffered solutions increased strongly. The concentration of 3
      DG in the chamber containing glucose In double-chamber bags increased between pH
      3.0 and 5.0 by a factor of 6. 3-Deoxyglucosone concentrations in commercially
      available products vary greatly, reflecting the different pH values of these
      products. A time- and temperature-dependent reaction leads to a reduction in 3-DG
      and an increase in 5-hydroxymethyl-furan-2-carbaldehyde during storage.
      CONCLUSION: Acetaldehyde is produced by a reaction that requires both lactate and
      glucose. Thus, its formation can be prevented by a separation of the reaction
      partners, glucose and lactate, in a double-chamber bag. In double-chamber bags,
      pH greatly influences the formation of 3-DG. Minimal formation is observed in the
      region of pH 3.0. This finding should be taken into account for the development
      of new double-chamber bag PDFs.

PMID- 12227394
TI  - Results of peritoneal equilibration test during treatment with polyglucose
      dialysis solution.
AB  - BACKGROUND: Results of peritoneal equilibration test (PET) suggest prolonged
      effect of polyglucose dialysis solution (PG-DS) on peritoneal permeability.
      OBJECTIVES: An evaluation of dialysate-to-plasma ratio (D/P) of urea, DIP
      creatinine, and D/D0 glucose (ratio of dialysate glucose at designated dwell time
      to dialysate glucose at 0 dwell time), and mass transfer area coefficients (KBD)
      of these solutes in PET before introduction, during administration, and after
      discontinuation of PG-DS hi patients treated with continuous ambulatory
      peritoneal dialysis (CAPD). DESIGN: Single-center prospective study with PG-DS;
      retrospective selection of the control group. SETTING: Peritoneal dialysis unit
      in a university hospital. PATIENTS: Fourteen patients (11 males; age 45.1 +/- 8.5
      years) treated with CAPD for 17.5 +/- 9.9 months. 7.5% PG-DS was used for the
      overnight exchange. After discontinuation of the PG-DS, standard dialysis
      solutions, as previously used, were reintroduced. The control group was selected
      to match both CAPO duration and peritoneal permeability of the patients in the PG
      DS group at the start of the study. METHODS: Standard PET was carried out at 1.6
      +/- 0.8 months before the introduction of PG-DS (study period I, n = 14), after
      1.2 +/- 0.6 months' use of PG-DS (study period II, n = 14), after 4.4 +/- 0.8
      months' use of PG-DS (study period Ill, n = 11), after 8.8 +/- 2.2 months' use of
      PG-DS (study period IV, n = 9), and at 2.0 +/- 0.6 months after PG-DS
      discontinuation (study period V, n = 11). Patients in the control group underwent
      PET at similar time intervals (control periods I-V). RESULTS: In the PG-DS group,
      a tendency toward increased peritoneal permeability for urea and creatinine was
      shown during the consecutive study periods. D/D0 glucose was significantly higher
      only in the PET performed during use of PG-DS (periods II-IV) compared to results
      obtained in period I. In the control group, both D/P and KBD of both urea and
      creatinine remained unchanged, but K90 glucose was higher in the first 2 hours of
      the PET in control period V compared to respective values in control period III.
      CONCLUSION: Changes in peritoneal permeability are observed In CAPD patients
      treated with PG-DS. These changes may be at least partially related to the
      administration of polyglucose.

PMID- 12227395
TI  - Comparison of a 2.5% and a 4.25% dextrose peritoneal equilibration test.
AB  - BACKGROUND: Ultrafiltration (UF) failure develops over time in some patients on
      peritoneal dialysis. The workup of UF failure can be difficult and the 4.25%
      peritoneal equilibration test (PET) has been suggested to be more useful than the
      2.5% PET for the workup of UF failure. It is unknown how a 4.25% PET compares to
      a 2.5% PET in individual patients. OBJECTIVES: To assess the differences in drain
      volumes and sodium sieving using a 4.25% PET compared to a 2.5% PET, and to
      determine whether peritoneal transport rates, in terms of dialysate-to-plasma
      (D/P) ratios, are comparable between the two. DESIGN: Pilot study with each
      patient serving as his or her own control. SETTING: Outpatient dialysis facility
      of Wake Forest University Baptist Medical Center. PATIENTS: 47 patients, all of
      whom had a 2.5% PET and a 4.25% PET performed within 1 week of each other.
      OUTCOME MEASURES: Dialysate-to-plasma ratios of urea and creatinine, dialysate
      total protein, and dialysate glucose compared to time zero (D/D0) at 0, 2, and 4
      hours. Four-hour drain volumes and sodium sieving at 2 hours were also measured.
      RESULTS: There was reproducibility between the 2.5% and 4.25% PET for D/P ratios
      of urea and creatinine and for dialysate total protein. There were expected
      differences in drain volume, sodium sieving, and D/D0 glucose between the two
      methods. CONCLUSIONS: The use of a 4.25% PET may be more useful for the workup of
      UF failure because of the accentuation of drain volume and sodium sieving, while
      remaining useful for prescription management.

PMID- 12227397
TI  - Semipermeability imparted by surface-active phospholipid in peritoneal dialysis.
AB  - OBJECTIVE: It has previously been demonstrated that a lining of surface-active
      phospholipid (SAPL) is reversibly bound (adsorbed) to normal peritoneal
      mesothelium. The lining acts as a boundary lubricant and release (anti-stick)
      agent preserving mechanical Integrity of the epithelial surface. In a review of
      clinical trials on the use of SAPL (akin to "surfactant") to restore
      ultrafiltration (UF) in patients on peritoneal dialysis (PD), speculation is
      that, by adsorption, the SAPL lining might also be Imparting the semipermeability
      vital for UF. DESIGN: To evaluate the hypothesis, SAPL harvested from the spent
      dialysate of 5 patients with normal UF was deposited onto a porous, inert medium,
      and the resulting 7 "membranes" were clamped in an Ussing chamber used as an
      osmometer. RESULTS: With every "membrane," a clinical concentration of glucose
      (2.5%) was able to induce a statistically significant osmotic pressure when
      dialyzed against saline. We also demonstrated how synthetic SAPL--in the form of
      dipalmitoyl phosphatidylcholine (DPPC) and an admixture of DPPC with
      phosphatidylglycerol (PG) called artificial lung-expanding compound (ALEC)-
      imparts greater osmotic pressure In proportion to an Increasing glucose gradient.
      Our findings prove that human peritoneal SAPL has the physical capability to
      Impart semipermeability when adsorbed to a surface. COMMENT: As a lipid lining,
      adsorbed SAPL could also explain the high permeability of the natural membrane to
      lipophilic substances in PD. Administered as a very fine powder or as a solution
      in a lipid solvent, ALEC offers a potential treatment for restoring UF, if
      applied during the interdialytic Interval. In various physical forms, ALEC and
      DPPC have both been widely used for two decades with complete safety in the
      treatment of respiratory distress syndrome in newborns. The question of
      formulation of exogenous SAPL In restoring UF Is discussed as a complex
      physicochemical compromise between the higher surface activity of saturated
      phosphatidylcholine and its lower solubility in water.

PMID- 12227396
TI  - Risk factors for early mortality in U.S. peritoneal dialysis patients: impact of
      residual renal function.
AB  - BACKGROUND: Potential risk factors for 1-year mortality, including the peritoneal
      component of dialysis dose, residual renal function, demographic data,
      hematocrit, serum albumin, dialysate-to-plasma creatinine ratio, and blood
      pressure, were examined in a national cohort of peritoneal dialysis patients
      randomly selected for the Centers for Medicare and Medicaid Services End-Stage
      Renal Disease (ESRD) Core Indicators Project. METHODS: The study involved
      retrospective analysis of a cohort of 1,219 patients receiving chronic peritoneal
      dialysis who were alive on December 31, 1996. RESULTS: During the 1-year follow
      up period, 275 patients were censored and 200 non censored patients died. Among
      the 763 patients who had at least one calculable adequacy measure, the mean [+/-
      standard deviation (SD)] weekly Kt/V urea was 2.16 +/- 0.61 and the mean weekly
      creatinine clearance was 66.1 +/- 24.4 L/1.73 m2. Excluding the 365 patients who
      were anuric, the mean (+/- SD) urinary weekly Kt/V urea was 0.64 +/- 0.52
      (median: 0.51) and the mean (+/- SD) urinary weekly creatinine clearance was 31.0
      +/- 23.3 L/1.73 m2 (median: 26.3 L/1.73 m2). By Cox proportional hazard modeling,
      lower quartiles of renal Kt/V urea were predictive of 1-year mortality; lower
      quartiles of renal creatinine clearance were of borderline significance for
      predicting 1-year mortality. The dialysate component of neither the weekly
      creatinine clearance nor the weekly Kt/V urea were predictive of 1-year
      mortality. Other predictors of 1-year mortality (p < 0.01) included lower serum
      albumin level, older age, and the presence of diabetes mellitus as the cause of
      ESRD, and, for the creatinine clearance model only, lower diastolic blood
      pressure. CONCLUSION: Residual renal function is an important predictor of 1-year
      mortality in chronic peritoneal dialysis patients.

PMID- 12227398
TI  - Peritoneal function and adequacy calculations: current programs versus PD
      Adequest 2.0.
AB  - OBJECTIVE: Our current programs (CPs) were compared to PD Adequest 2.0 (PD-A) for
      calculations of peritoneal membrane transport and dialysis adequacy. DESIGN:
      Thirty peritoneal equilibration tests (PETs) and 24-hour balances (24hBs) were
      conducted and calculated using our CPs and PD-A. PATIENTS AND METHODS: Thirty
      hospital-controlled peritoneal dialysis (PD) patients were studied. The inclusion
      of correction factors (for glucose or plasmatic water) and of residual volume,
      and the use of 3 or 6 peritoneal samples were analyzed to discover the
      differences between programs. The main outcome measures were peritoneal
      permeability and adequacy parameters, evaluated by Student t-test (mean and
      paired comparisons) and linear regression for correlation. RESULTS: No
      significant differences were found in D/P values for small solutes. At the first
      step, mass transfer area coefficient (MTAC) urea and MTAC creatinine were
      significantly higher in DP-A than in CP, but MTAC glucose did not differ. The
      causes of differences were: (1) inclusion of a correction factor for aqueous
      plasmatic concentration of small solutes in CP; (2) lack of Inclusion of residual
      volume in peritoneal volumes in CP; and (3) use of 6 peritoneal samples in CP
      versus 3 in PD-A. At the second step, when the input data were made equivalent
      for both programs, the differences disappeared for MTAC urea, creatinine, and
      glucose (mean comparison), but creatinine and glucose remained different by
      paired comparison. Similar results were obtained when a correction for plasmatic
      aqueous concentration was applied to the data in both programs [MTAC urea: 22.60
      +/- 4.27 ml/min (CP) vs 22.43 +/- 4.61 mL/min (PD-A), nonsignificant, r= 0.97;
      MTAC creatinine: 9.76 +/- 3.83 mL/min (CP) vs 10.61 +/- 3.07 mL/min (PD-A),
      nonsignificant, r = 0.98; MTAC glucose: 13.30 +/- 3.12 mL/min (CP) vs 11.87 +/-
      3.41 m/min (PD-A), nonsignificant, r= 0.92]. Creatinine and glucose were
      different by paired t-test. No significant differences were found in Kt/V and
      urea generation rate. Weekly creatinine clearance [WCCr: 70.71 +/- 16.71 L (CP)
      versus 79.33 +/- 18.73 L (PD-A), p < 0.001] and creatinine generation rate [CrGR:
      0.56 +/- 0.18 mg/min (CP) versus 0.61 +/- 0.19 mg/min (PD-A), p < 0.001) were
      significantly higher in PD-A than In CP owing to the lack of creatinine
      correction according to glucose concentration In the PD-A adequacy program.
      Finally, normalized protein nitrogen appearance according to Bergstrom [1.09 +/-
      0.20 g/kg/d (CP) versus 1.03 +/- 0.21 g/kg/d (PD-A), p = 0.01] was different
      owing to the different algorithms and normalization method: standardized body
      weight in CP and actual body weight in PD-A. CONCLUSIONS: Provided that
      equivalent data are used, PD-A and CP yield similar results. The PD-A program
      needs external correction of data input: (1) for plasmatic water concentration in
      MTAC calculations, and (2) for peritoneal glucose interference with creatinine
      analysis (Jaffe method) In WCCr and CrGR calculations; otherwise, It may give
      falsely optimistic results.

PMID- 12227399
TI  - Association of anion gap with thyroid dysfunction and nodular goiter in CAPD
      patients.
AB  - OBJECTIVE: To investigate the association of clinical parameters and serum anion
      gap with thyroid dysfunction and nodular goiter in continuous ambulatory
      peritoneal dialysis (CAPD) patients. DESIGN: Cross-sectional study. SETTING:
      Single dialysis unit and outpatient clinic. PATIENTS: This study Included 89
      uremic patients on CAPD. Gender ratio was 50 males to 39 females (M/F = 1.28);
      mean age was 54.8 years. MAIN OUTCOME MEASURES: We investigated the prevalence of
      nodular goiter and thyroid dysfunction with a 10-MHz high-frequency ultrasound
      scanner and immunoassay kits. RESULTS: Nodular goiter was detected in 52.8%
      (47/89) of the CAPD patients. Patients with nodular goiter were older than those
      without goiter (57.7 vs 51.5 years, p < 0.05). Nodular goiter was found more
      frequently in females than in males (66.7% vs 44.0%, p < 0.05). Patients with
      nodular goiter had longer duration of CAPD than patients without goiter (51.6 +/-
      42.9 vs 31.0 +/- 28.1 months, p < 0.02). In addition, CAPD patients with goiter
      had a higher serum anion gap (AG) (16.8 +/- 3.3 vs 14.0 +/- 4.5 mEq/L, p < 0.02)
      and a lower weekly creatinine clearance (55.9 +/- 12.6 vs 64.6 +/- 21.1
      L/week/1.73 m2, p < 0.05) than patients without goiter. As serum AG gradually
      Increased, significant alteration of thyroid parameters developed In the
      following sequence: (1) reduction of total T3 level at an AG level of 15, (2)
      elevation of thyrotropin (TSH) and Increased prevalence of goiter at an AG of 18,
      and (3) reduction of free T4 and total T4 levels and elevation of TSH, with
      further increased frequency of goiter at an AG of 20 mEq/L. CONCLUSION: According
      to this study, age, gender, dialysis duration, serum AG, and weekly creatinine
      clearance are correlated with prevalence of goiter in CAPD patients. Sequential
      alteration of thyroid function and Increasing frequency of nodular goiter
      correlated with higher serum AG. There are two explanations for this correlation:
      the level of serum AG may be an indirect index of the level of serum goitrogens,
      and higher serum AG and Increased frequency of nodular goiters might be a
      reflection of loss of residual renal function. Therefore, thyroid function
      screening and goiter detection using ultrasound should be considered when
      examining CAPD patients with progressively elevating serum anion gap.

PMID- 12227400
TI  - Selenium metabolism in patients on continuous ambulatory peritoneal dialysis.
AB  - BACKGROUND: Selenium is an essential trace element for living organisms. In many
      publications, researchers express concern about a possible Se deficiency in
      patients with end-stage chronic renal failure (ESCRF) undergoing continuous
      ambulatory peritoneal dialysis (CAPD). However, in a number of published
      articles, the data provide no evidence that patients under CAPD develop Se
      deficiency. OBJECTIVE: We investigated Se metabolism in ESCRF patients on CAPD.
      SETTING: The study was carried out at the Department of Propaedeutic Surgery,
      Athens University; the Laboratory for Material Analysis of the Nuclear Physics
      Institute; and the State General Hospital, Athens, Greece. PATIENTS AND METHODS:
      The study group included 24 patients on CAPD treatment, 14 ESCRF patients, and 17
      healthy controls. We measured the Se and Fe content of serum, blood, and
      erythrocytes. We also measured hematocrit, serum total proteins and albumins, and
      Se in dialysate effluent. RESULTS: As compared with healthy subjects, the ESCRF
      and CAPD patients exhibited reduced serum concentrations of Se. However,
      considering the difference in hematocrit values, the total serum-transported Se
      per liter of blood was close to normal. Erythrocyte Se proved normal for both
      groups. The measured Se in the spent effluent indicates that patients under CAPD
      receive approximately 100 microg Se from their daily diet, as normal subjects do.
      The Se measurement data from the effluent indicate that 90% of the Se carried by
      the serum is bound to albumins and that only the remaining 10% is in the form of
      low molecular weight selenate, free to pass the peritoneal membrane. Of the 24
      CAPD patients studied, 4 patients (all women) showed extremely low Se serum
      levels. Data suggest that those low levels are more likely due to the
      significantly lower serum albumin levels in the 4 patients than to an
      insufficient dietary intake. CONCLUSIONS: Data from the present experimental work
      suggest that patients undergoing CAPD receive the necessary quantities of Se from
      their regular diet. The data contradict statements in the relevant literature
      that CAPD patients develop Se deficiency.

PMID- 12227401
TI  - Epidemiology of GB virus c/hepatitis g virus infection in patients on peritoneal
      dialysis.
AB  - BACKGROUND: A new genus in the family Flaviviridae has recently been discovered;
      it has provisionally been designated GBV-C/HGV. As determined by virologic
      techniques [reverse-transcription polymerase chain reaction (RT-PCR)], infection
      with GBV-C/HGV is frequent in renal transplant (RT) recipients and in patients on
      chronic hemodialysis (HD). The epidemiology of GBV-C/HGV infection in patients on
      peritoneal dialysis is scarce and mostly based on RT-PCR technology. PURPOSE: We
      report on the prevalence (as detected by serologic and virologic techniques) and
      the risk factors for GBV-C/HGV infection in a cohort of patients on continuous
      ambulatory peritoneal dialysis (CAPD). We also tested a control group of blood
      donors. METHODS: Infection by GBV-C/HGV was assessed by serologic and virologic
      techniques. Cases of GBV-C/HGV viremia (GBV-C/HGV RNA) were detected by RT-PCR.
      Antibodies to the envelope protein of GBV-C/HGV (anti-E2 GBV-C/HGV antibody) were
      analyzed by serologic methods. RESULTS: We found a high frequency [17/85 (20%)]
      of GBV-C/HGV. The rates of GBV-C/HGV viremia and anti-E2 GBV-C/HGV positivity
      were 10.5% (9/85) and 10.5% (9/85) respectively. In most patients [17/18 (94%)],
      the presence of anti-E2 GBV-C/HGV antibody was associated with clearance of GBV
      C/HGV from serum. No relationship was noted between anti-E2 GBV-C/HGV antibody
      (or GBV-C/ HGV viremia) and age, sex, race, time on dialysis, anti-HCV antibody,
      HBsAg status, and anti-HIV positivity. The frequency of GBV-C/HGV infection in
      CAPD patients was much higher than that in blood donors, even if the difference
      did not approach statistical significance. No associations between GBV-C/HGV
      positivity and biochemical liver tests [aminotransferase and gamma glutamyl
      transpeptidase (GGT)] were apparent. CONCLUSIONS: Infection by GBV-C/HGV as
      detected by RT-PCR and anti-E2 antibody was common in patients on CAPD and in
      controls alike. No association was seen between GBV-C/HGV and various demographic
      or clinical factors. The clinical significance of GBV-C/HGV in CAPD remains
      unclear. Larger investigations are in progress.

PMID- 12227402
TI  - Multicenter survey on hydration status and control of blood pressure in Japanese
      CAPD patients.

PMID- 12227403
TI  - Predictors of loss of residual renal function in peritoneal dialysis patients.

PMID- 12227404
TI  - Severe hemoperitoneum caused by spontaneous liver rupture: a case report.

PMID- 12227405
TI  - Linezolid stability in peritoneal dialysis solutions.

PMID- 12227406
TI  - Ureaplasma urealyticum CAPD peritonitis following insertion of an intrauterine
      device: diagnosis by eubacterial polymerase chain reaction.

PMID- 12227407
TI  - Relapsing Bacillus cereus peritonitis in two patients on peritoneal dialysis.

PMID- 12227408
TI  - Hyperlipidemia in children on peritoneal dialysis: effect of energy intake on
      serum triglyceride.

PMID- 12227409
TI  - CAPD as treatment of chronic debilitating hemodialysis hypotension.

PMID- 12227410
TI  - Peritonitis and pancreatic abscess in a CAPD patient.

PMID- 12227411
TI  - Small bowel obstruction due to localized Tenckhoff catheter-related adhesions.

PMID- 12227412
TI  - Aortoduodenal fistula in a patient undergoing peritoneal dialysis.

PMID- 12227413
TI  - Literature: May-June 2002.

PMID- 12227414
TI  - ELISA inhibition assay for the quantitation of antigenic protein in natural
      rubber latex.
AB  - Evaluating allergenicity of natural rubber latex (NRL) products is essential for
      the successful reduction of the consumer's exposure to potentially allergenic NRL
      proteins. We have developed an ELISA Inhibition method for the quantitation of
      extractable proteins from NRL products which has good sensitivity and
      specificity. The method utilizes rabbit anti-NRL protein serum as a detection
      mechanism. The source of NRL proteins for immunization and as a reference protein
      in the assay is ammoniated raw latex (AL). By comparison with the Western blot
      analysis of the rabbit sera, it appears that the ELISA detects most of the latex
      proteins present in extracts. To investigate, further, this assumption, we
      compared the ELISA Inhibition test with two other methods for total protein
      measurement. We also compared the values generated by the ELISA Inhibition test
      with other immunological methods for quantitation of antigenic and allergenic
      proteins. Comparisons were performed with 15 extracts from randomly selected
      surgical and examination gloves. The samples were coded separately for each test
      to insure the objectivity of evaluation. The antigenic protein values obtained by
      the ELISA Inhibition test correlated best with the HPLC amino acid analysis
      (correlation coefficient (cc) = 0.79) and with the LEAP assay (cc = 0.97). The
      antigenic protein levels obtained by the ELISA test were 3-10 times lower than
      those obtained by the HPLC analysis. A lesser correlation was observed with the
      Modified Lowry assay (cc = 0.45), which is likely due to chemical interference
      bias in the Lowry method. Our findings suggest that the antigenic proteins
      measured by the ELISA Inhibition test described here more closely represent the
      measure of the total protein content in the extracts. It is important to note
      that the relative values obtained by this method are lower than the values
      obtained by other total protein methods, possibly due to a large number of small
      peptides present in NRL products, that would only be measured by the chemical
      method.

PMID- 12227415
TI  - A new model ELISA, based on two monoclonal antibodies, for quantification of
      fatty acid synthase.
AB  - A new model ELISA, based on two monoclonal antibodies, was developed for the
      quantification of fatty acid synthase (FAS). In this sandwich assay, a monoclonal
      antibody M6 was used as a capture on Nunc MaxiSorp ELISA/EIA Modules and another
      monoclonal antibody M3, labeled with biotin, was used as a detection antibody.
      More than 10 molecules of biotin were labeled on the anti-FAS monoclonal antibody
      using modified biotinylation conditions. The within- and between-run CVs were
      less than 10%, and the detection limit was 3.22 ng/mL. Recoveries were 98.54
      121.95%, averaging 106.05%. The average FAS concentration obtained from the total
      55 healthy volunteers blood was 4.07 +/- 1.81 ng/mL, 4.25 +/- 2.14 ng/mL in women
      (n = 37) and 3.70 +/- 0.74 ng/mL in men (n = 18). When compared with the
      previously developed polyclonal-monoclonal ELISA, a different pattern of FAS
      levels was observed in the supernatant of two cultured breast cancer cell lines
      in a time course study and there was no linear correlation between the two assays
      using 215 human blood samples. Thus, this new model FAS-ELISA could be used as an
      independent assay in measuring clinical samples. In summary, this monoclonal
      monoclonal FAS-ELISA is sensitive, accurate, and precise in quantification of
      fatty acid synthase and has potential as a complementary tool in testing clinical
      samples.

PMID- 12227416
TI  - ELISA for quantitation of serum C-erbB-2 oncoprotein in breast cancer patients.
AB  - C-erbB-2 is a protooncogene that is overexpressed in various cancers, either due
      to its amplification and/or increased transcription, and has been associated with
      more aggressive disease and a poor clinical prognosis in 20-30% of patients with
      breast cancer. Besides the prognostic factors such as tumor size, tumor grade,
      lymph node status, etc., which are significant in the management of breast
      cancer, C-erbB-2 level might also serve as an additional factor.
      Immunohistochemistry is the most frequently used method to study the expression
      of C-erbB-2 in breast cancer. We have generated a panel of monoclonal antibodies
      against C-erbB-2 oncoprotein with a view to evaluate their application for the
      diagnosis and therapy of breast cancer. In the present study, a simple,
      quantitative sandwich ELISA has been developed that uses two monoclonal
      antibodies directed against the extracellular domain of C-erbB-2 product,
      designated as CIBCgp185 as the capture antibody and CIBCHER-2 as the detector
      antibody. C-erbB-2 protein, isolated from BT474 cells, a human breast carcinoma
      cell line with high expression of C-erbB-2 and purified by Concanavalin A
      Sepharose 4B affinity chromatography and HPLC has been used to develop the ELISA
      procedure. Sera samples of 150 healthy women donors and of 300 breast cancer
      patients with different histological types of malignancies have been analysed.
      The control women had serum C-erbB-2 in the range of 4.0-13.2 ng/mL, whereas the
      300 breast cancer patients studied had a range of 4.8-75.2 ng/mL with a cut off
      value of 13.8 ng/mL. Our study showed that 18.6% of breast cancer patients had
      elevated levels of circulating C-erbB-2. These results might suggest that the
      serum C-erbB-2 level can be used as a potential tumor marker for breast cancer
      and that the Sandwich ELISA procedure might serve as an excellent alternative to
      immunohistochemistry in the near future.

PMID- 12227417
TI  - Field trial of the brucellosis fluorescence polarization assay.
AB  - Fluorescence polarization assay (FPA) is a homogeneous technique which was
      applied to the serological diagnosis of bovine brucellosis. Because of its
      simplicity and because it may be performed very rapidly, it was an ideal test to
      adapt to field use. The FPA was used to test cattle on six dairy farms in Baja
      California, Mexico. Anticoagulated blood, serum, and milk were collected from
      each animal. The anticoagulated blood was tested immediately on the farm while
      serum and milk were tested subsequently in the laboratory. Cattle on one farm (n
      = 140) were thought not to be infected with Brucella abortus and the other farms
      were thought to have high prevalence of the infection. The whole blood FPA
      (FPA(bld)) did not detect antibody in any of the cattle on the first premise.
      This finding was confirmed using a number of other serological tests, including
      the buffered antigen plate agglutination test, the complement fixation test, the
      indirect and competitive enzyme immunoassays, and the FPA using serum and milk.
      Cattle on the other premises (n = 1122) were tested in a similar fashion. The
      sensitivity of the FPA(bld), relative to the serum FPA (considered the definitive
      test), was 99.1% and the relative specificity of the FPA(bld) was 99.6%. These
      results compared favourably with those obtained using the other serological
      tests.

PMID- 12227418
TI  - Establishment of a highly sensitive leptin radioimmunoassay and detection of
      increased leptin levels in hyperlipidemia and pregnancy.
AB  - The highly effective antibody has been obtained by immunizing rabbits with
      recombinant leptin many times. The leptin is iodinated with the chloramine-T
      method and purified with a Sephadex-G25 chromatography column. The reaction
      between antigen and antibody is carried out by a one-step balance method and
      cultured at 4 degrees C for 24 h; the binding and free antigen was then separated
      by PR reagent. The determining range of this method is about 0.5-24 ng/mL;
      limited detection level is 0.45 ng/mL, relative standard deviation in a group,
      and among groups, are less than 5.4% and 8%, respectively. The level of blood
      leptin in 277 samples of normal persons, in 112 samples of overweight persons
      (weight/hieght m2 > or = 25) and 224 samples of hyperlipidemic patients have been
      measured by this method. It is demonstrated that the level of blood leptin in
      males is much lower than that of the females, and becomes elevated with increased
      age. Serum leptin level in overweight persons and hyperlipidemic patients is also
      much higher than that of normal groups (P < 0.01). Serum leptin of 21 workers in
      our lab at 8:00 AM and 4:00 PM has been tested. It was found that there are no
      differences between the two time points. The same results are obtained within age
      groups. Leptin levels of pregnant women's serum is higher than those of the
      control group (P < 0.001). Leptin in newborn's serum is significantly lower than
      those of mothers (P < 0.01). There is no obvious correlation between leptin level
      of mother and newborns by correlation analysis (r = 0.19, P > 0.05). The body
      weight and body weight index of pregnant women are well correlated with their
      serum leptin levels (r = 0.33 and 0.35, P < 0.05). The body weight and body
      weight index of newborns are well correlated with their serum leptin levels (r =
      0.54 and 0.49, P < 0.001). The serum leptin level of pregnant women is not
      correlated with newborn's body weight (r = 0.10). These results have shown that
      the proposed method is stable, simple, and specific, being sensitive enough to
      determine leptin levels in human serum or plasma.

PMID- 12227419
TI  - Thermostable alpha-amylase conjugated antibodies as probes for immunodetection in
      ELISA.
AB  - Thermostable alpha-amylase from B. licheniformis has been conjugated with high
      efficiency to goat antibodies against human, mouse, and rabbit immunoglobulins to
      prepare second-step reagents which can be used in Enzyme Linked Immunosorbent
      Assays (ELISA). Various conjugation methods, such as one- and two-step
      glutaraldehyde coupling and cross-linking, using heterobifunctional reagents such
      as sulfosuccinimidyl-4-(N-maleimidomethyl)-cyclohexane-1-carbonate (sulfo-SMCC)
      and N-succinimidyl-S-acetylthioacetate (SATA), yielded active alpha-amylase
      labeled second antibodies. Such conjugates had molecular sizes ranging between
      200-300 kDa. Filter sterilized solutions of conjugates, when stored at 37 degrees
      C for two weeks, retained 32% of their biological activity and were thermostable
      even after keeping for 1 h at 90 degrees C.

PMID- 12227420
TI  - Kinetics and equilibrium in the immunoradiometric assay (IRMA) of thyroglobuline.
AB  - This paper studies the kinetics of the thyroglobuline reaction with its specific
      antibody immobilised on the inner wall of the reaction tube, and the subsequent
      binding of the immunocomplex formed with a second 125I-labelled antibody. These
      reactions are used in the immunoradiometric determination of thyroglobuline.
      Independent variables were analyte and labelled antibody, temperature, viscosity,
      and the medium's ionic strength. For the global process, mono-exponential
      kinetics were found to be dependent on the concentrations, such dependence
      fitting with the models discussed in the paper. Viscosity results clearly
      indicate its negative influence on the direct reaction rate. Ionic strength shows
      noticeable, but not too relevant, effects, which suggests that the variation
      caused by the glycerol addition is not due to the influence of the dielectric
      constant of the solutions used. The effect of temperature shows activation
      parameters similar to the viscous flow energy of water, which suggests diffusion
      control for the global process.

PMID- 12227421
TI  - Identification of antigenic and allergenic natural rubber latex proteins by
      immunoblotting.
AB  - Quantitation of proteins in finished natural rubber latex (NRL) products is
      essential in predicting their allergenic potential. The ASTM standard Modified
      Lowry method for measuring total protein content has been used for several years.
      Most recently, ASTM published a standard for more sensitive and more specific
      enzyme immunoassay for quantitation of antigenic NRL proteins. It is an ELISA
      inhibition assay, using rabbit anti NRL sera. Since the measurement of proteins
      in this method depends on recognition capacity of rabbit antibodies, the
      selection of an appropriate protein source for rabbit immunization is crucial for
      the accuracy of such test. In this study, we evaluated the composition of NRL
      proteins from ammoniated (AL) and nonammoniated (NAL) raw latex and from finished
      NRL products, and compared the effectiveness of sera from rabbits immunized with
      NRL proteins, to react with those extracts. Immune rabbit sera were analyzed by
      immunoblotting against extracts of several samples of AL, NAL, and glove
      proteins. In the NAL extracts, we identified 26-28 protein bands by SDS-PAGE. AL
      samples had between 6 and 9 bands with a great variation in the band positions
      among the samples. The Western blot analysis showed that anti-AL rabbit serum
      reacted with 4-9 protein bands in various AL extracts. The highest intensity of
      reaction was observed with the extract used to immunize the rabbits. Similar
      reaction was observed with anti-NAL serum. However, when the antisera were
      blotted against NAL extracts, anti-NAL serum reacted more strongly and with a
      larger number of proteins than anti-AL serum. In summary, anti-NAL serum
      recognized an equal number of proteins in AL extract as anti-AL serum. However,
      anti-AL serum recognized fewer protein molecules in NAL extract than anti-NAL
      serum. Our findings suggest that NAL extract contains more individual proteins
      than other extracts, and sera from rabbits immunized with this antigen have a
      greater capacity to react with a wide spectrum of NRL proteins. This finding may
      be helpful in selecting the representative reference antigen and antiserum for
      further efforts in NRL protein quantitation.

PMID- 12227422
TI  - Stabilization of penicillinase-hapten conjugate for enzyme immunoassay.
AB  - The influence of various additives, such as organic solvents, polyhydric
      alcohols, salts, polymers, and cross-linker, on the stability and storage ability
      of penicillinase-morphine conjugate was studied in liquid and solid (freeze
      dried) states. The results of these experiments showed that using low
      concentrations of CaCl2 (0.1-0.2%) could stabilize enzyme activity in both states
      for more than seven months. The immunoreactivity of antigen toward the antibody
      did not change significantly. However, a cross-linker such as glutaraldehyde and
      various additives such as dimethylsulfoxide, glycerol, polyethylene glycol,
      gelatin, dextran, ammonium sulfate, lactose, and sucrose did not have any effect
      on stability. In addition, it was found that the presence of lactose and sucrose
      in the lyophilization procedure gives a significant amount of protection to the
      enzyme, which could last for a period of seven months and preserve almost 95% of
      the enzyme activity, as well as immunoreactivity of the tracer molecule.

PMID- 12227423
TI  - Preparation and sensitization of polystyrene latex beads by some antigens and
      antibodies. Factors affecting sensitivity and specificity of latex agglutination
      tests.
AB  - Polystyrene latex beads were polymerized at two different pH (7.3 and 9.5) and
      their ability to create latex agglutination systems were studied. Sensitization
      of these latexes by DNA, antibodies to C-reactive protein, myoglobin, and human
      IgG. was conducted. Sensitivity and specificity of these systems were compared.
      Practical recommendations are given for preparation of such systems.

PMID- 12227424
TI  - The cold origin of life: A. Implications based on the hydrolytic stabilities of
      hydrogen cyanide and formamide.
AB  - It has been suggested that hydrogen cyanide (HCN) would not have been present in
      sufficient concentration to polymerize in the primitive ocean to produce nucleic
      acid bases and amino acids. We have measured the hydrolysis rates of HCN and
      formamide over the range of 30-150 degrees C and pH 0-14, and estimated the
      steady state concentrations in the primitive ocean. At 100 degrees C and pH 8,
      the steady state concentration of HCN and formamide were calculated to be 7 x 10(
      13) M and 1 x 10(-15) M, respectively. Thus, it seems unlikely that HCN could
      have polymerized in a warm primitive ocean. It is suggested that eutectic
      freezing might have been required to have concentrated HCN sufficiantly for it to
      polymerize. If the HCN polymerization was important for the origin of life, some
      regions of the primitive earth might have been frozen.

PMID- 12227426
TI  - Phosphorylation of adenosine with trimetaphosphate under simulated prebiotic
      conditions.
AB  - The phosphorylation of adenosine with trimetaphosphate in solution, in solid
      phase and using wet-dry cycles was carried out and it was found that wet-dry
      cycles were the most efficient. The catalytic effects of some metal ions on the
      phosphorylation were also studied and it was discovered that Ni(II) is the most
      effective. The combination of wet-dry cycles (4 cycles) and catalysis by Ni(II)
      led to an unprecedented high conversion of adenosine to phosphorylated products
      (30%) near neutral pH. The main phosphorylated products were 2',3'-cyclic AMP
      (10.4%) and 5'-ATP (13.0%).

PMID- 12227425
TI  - The cold origin of life: B. Implications based on pyrimidines and purines
      produced from frozen ammonium cyanide solutions.
AB  - A wide variety of pyrimidines and purines were identified as products of a dilute
      frozen ammonium cyanide solution that had been held at -78 degrees C for 27
      years. This demonstrates that both pyrimidines and purines could have been
      produced on the primitive earth in a short time by eutectic concentration of HCN,
      even though the concentration of HCN in the primitive ocean may have been low. We
      suggest that eutectic freezing is the most plausible demonstrated mechanism by
      which HCN polymerizations could have produced biologically important prebiotic
      compounds.

PMID- 12227427
TI  - Glycine and diglycine as possible catalytic factors in the prebiotic evolution of
      peptides.
AB  - Mutual catalytic effects within the Salt-Induced Peptide Formation (SIPF)
      Reaction might be one little puzzle piece in the complicated process of the
      formation of complex peptidic systems and their chemical evolution on the
      prebiotic earth. The catalytic effects of glycine and diglycine on the formation
      of dipeptides from mixed amino acid systems in the SIPF Reaction was investigated
      for systems with leucine, proline, valine and aspartic acid and showed to result
      in a significant increase of the yield of the majority of the produced
      dipeptides. The results of the experiments strongly confirm previous theories on
      the catalytic mechanism and show the ability of the SIPF Reaction to produce a
      very diverse set of peptide products with relevance to the formation of a
      biosphere.

PMID- 12227428
TI  - The asymmetry of organic aerosol fission and prebiotic chemistry.
AB  - We examine the prebiotic applicability of our recent analysis of the fission of
      an atmospheric aerosol particle coated with an organic film. The fission is made
      possible by the free energy change upon compression of the exterior monolayer
      film on the parent particle, which overcomes the increase in surface area
      associated with the production of two spherical daughter particles. Asymmetric
      division into a larger and a smaller particle becomes possible following
      surfactant film collapse. The size of the airborne parent particle is determined
      by the balance between aerodynamics and gravity, while the ratio of the radii of
      the daughters is determined by the compression characteristics of the amphiphilic
      molecules comprising the parent film. For an Earth atmosphere of one bar surface
      pressure, the larger and smaller daughters have the sizes of a single-celled
      bacterium and of a virus respectively. Chemical differentiation between the
      daughters is possible.

PMID- 12227429
TI  - Possible impact of a primordial oil slick on atmospheric and chemical evolution.
AB  - Low molecular weight liquid hydrocarbons from various sources, could have formed
      an oil layer covering the primeval ocean (present already 4.0-4.4 x 10(9) yr
      ago), preventing water from evaporating into the atmosphere. Water from other
      sources, precipitated by cold traps at higher altitude in the atmosphere, becomes
      trapped in the ocean. In a thereby more dry and presumably reducing atmosphere
      (before 3.9 x 10(9) yr ago) even more hydrocarbons, as well as reactive molecules
      will form. An oil layer can possibly act as a dry solvent for reactions, where
      the reactive molecules can produce monomers and condensing agents. Monomers and
      eventual polymers formed could become strongly concentrated at the oil-water
      interface, favouring molecular interactions at high mobility and low dilution,
      without exposure to the destructive action of UV-light. Increased water leakiness
      of the oil layer due to accumulation of polar molecules within, would lead to
      photooxidation of liquid hydrocarbons, and subsequent emulsification at the oil
      water interface, forming cellular structures. The atmosphere would then have lost
      its reducing character.

PMID- 12227430
TI  - On the plausibility of a UV transparent biochemistry.
AB  - Some molecules, particularly aromatics, have high molar extinction coefficients
      at wavelengths in the damaging ultraviolet radiation region of the spectrum
      between 200 and 400 nm. Thus, under a UV radiation flux in which these
      wavelengths are represented, it could be argued that a selection pressure would
      exist for a UV transparent biochemistry in which they were not represented. This
      hypothesis is explored using data made available from proteomics, focusing
      particularly on tryptophan, against which a selection pressure could exist on
      present-day Earth as a result of its absorbance shoulder at wavelengths greater
      than 290 nm. The abundance of tryptophan in whole proteomes is lower than
      expected from the degeneracy of the genetic code. A lower usage of tryptophan is
      found in the cytochrome c oxidase polypeptide I of UV-exposed organisms compared
      to nocturnal and subterranean organisms, but not in ATP synthase chain A.
      Examination of the amino acid composition of photolyase, an enzyme that requires
      exposure to light to function, shows that the tryptophan abundances exceed those
      of the total proteome of most organisms and the abundances expected from the
      degeneracy of the genetic code. This is also true for cytochrome c oxidase,
      another enzyme that makes extensive use of the electron transfer properties of
      tryptophan. We suggest that the selection pressure for the use of tryptophan
      caused, among other factors, by the uses of delocalised pi-electrons that this
      aromatic provides in active sites and binding motifs outweighs the selection
      pressure for UV transparency. This trade-off explains the lack of conclusive
      evidence for a UV transparent selection pressure. We suggest that this trade-off
      applies to the stacked pi-electrons of DNA. It offers a solution to the long
      standing paradox of why the macromolecule responsible for the faithful
      replication of information has high absorbance in the damaging UV radiation
      region of the spectrum.

PMID- 12227431
TI  - Comments on 'concentration by evaporation and the prebiotic synthesis of
      cytosine'.
AB  - The claim by Nelson et al. (2001) that the reaction of cyanoacetaldehyde and urea
      provides 'an efficient prebiotic synthesis' of cytosine is disputed. The authors
      have not dealt with the important points presented in a criticism of this
      reaction (Shapiro, 1999): (1) The reactants undergo side reactions with common
      nucleophiles that appear to proceed more rapidly than cytosine formation, and (2)
      No reactions have been described thus far that would produce cytosine at a rate
      sufficient to compensate for its decomposition by deamination, and permit
      accumulation over extended periods of time. Instead, Nelson et al. have conducted
      'drying-down' experiments, in an effort to simulate evaporations on the early
      Earth, but the design of these experiments is flawed. The initial reactant
      concentrations are much higher than might be expected in a natural setting, and
      potentially interfering substances such as glycine, cyanide and thiols have been
      excluded. 'Drying beaches and drying lagoons' have been invoked as sites for such
      a reaction but no effort has been made to describe the characteristics of such
      sites or to estimate their frequency with reference to the present Earth. In the
      absence of contradictory data, the conclusion put forward in Shapiro (1999)
      remains valid: 'It was quite unlikely that cytosine played a role in the origin
      of life'.

PMID- 12227432
TI  - Is cyanoacetylene prebiotic?
AB  - Cyanoacetylene is an earlier intermediate in a proposed prebiotic synthesis of
      cytosine, while cyanoacetaldehyde is a later intermediate. There is no scientific
      basis for the claim that cyanoacetaldehyde is more plausibly prebiotic than
      cyanoacetylene in this context.

PMID- 12227433
TI  - Reduced response readiness delays stop signal inhibition.
AB  - This study examines the effect of response readiness on the stopping of motor
      responses. Thirteen subjects performed a primary task requiring a speeded choice
      reaction on go trials and response inhibition on nogo trials. An occasional cue
      informed subjects that a nogo trial was imminent but left them uncertain about
      the number of go trials separating the cue and the upcoming nogo trial. This
      setup was meant to create test episodes of reduced response readiness (i.e.,
      trial sequences initiated by the cue and terminated by the nogo signal) and
      control episodes, in which subjects were ready to execute a speeded choice
      reaction (i.e., trial sequences consisting only of go trials). During both
      episodes, a visual stop signal could occasionally and unpredictably follow go
      signal onset, instructing subjects to withhold their response to the go signal.
      Choice reactions on go trials were delayed during test episodes relative to
      control episodes. Most importantly, stop reactions were delayed, not facilitated,
      during test episodes compared to control episodes. These findings were taken to
      suggest that reduced readiness gives rise to more forceful responses that are
      then more difficult to inhibit.

PMID- 12227434
TI  - Reduced or increased influence of non-pertinent information in patients with
      schizophrenia?
AB  - We tested the ability of 18 patients with schizophrenia and 18 matched controls
      to filter non-pertinent information in orientation matching tasks. The non
      pertinent information consisted of pictures conveying semantic information. The
      pertinent information consisted of oriented line-segments drawn inside pictures
      or was represented by the overall orientation of the picture itself. The results
      showed that non-pertinent information interfered with performance of control
      subjects in all tasks. In contrast, non-pertinent information interfered with the
      performance of patients with schizophrenia to the same extent as that of matched
      controls only when non-pertinent and pertinent information was physically
      mingled, but not when they were separated. Yet, patients processed non-pertinent
      information in all experiments, as shown by reversed interference effects when
      non-pertinent and pertinent information was physically separated. These results
      suggest a deficit at linking physically distinct visual information in patients
      with schizophrenia. Additionally, performance was more impaired in patients with
      schizophrenia than in control subjects when the amount of displayed information
      increased. The results suggest the coexistence, and a possible relationship
      between attentional deficits and impairments at linking distinct visual
      information in patients with schizophrenia.

PMID- 12227435
TI  - The unbearable lightness of priming.
AB  - Repetition priming from text to isolated words has been difficult to observe. One
      explanation for this difficulty is that previous attempts to observe this type of
      priming have utilised conditions that normally reduce priming. Two experiments
      were conducted to evaluate this hypothesis. Experiment 1 involved participants
      being presented with words in isolation and in text passages. The words were then
      presented again in a lexical decision test. Results indicated that priming
      occurred as a result of exposure to both isolated words and words in text,
      although priming was greater in the word-word condition. Experiment 2
      investigated whether priming occurred in a lexical decision test on words that
      had been read prior to the test in Milan Kundera's novel "The Unbearable
      Lightness of Being." There was some evidence that participants who had read the
      book recently were faster at lexical decision to words from the book than
      participants who had not read the book. The two experiments therefore indicate
      that priming can occur from text to isolated words, although it is smaller in
      magnitude to that observed from word to word. Reasons for this difference, as
      suggested by Kirsner and Speelman (J. Exp. Psychol.: Learn. Mem. Cogn. 22 (1996)
      563) model of repetition priming, are discussed.

PMID- 12227436
TI  - Parametric coupling and generalized decoupling revealed by concurrent and
      successive isometric contractions of distal muscles.
AB  - In two experiments we examined the hypothesis of transient parametric coupling
      during the specification of peak forces of isometric contractions produced by the
      left and right hand. In the first experiment participants had to produce bimanual
      contractions with same and different target forces as rapidly as possible in
      response to an auditory signal; target forces were cued visually with variable
      cueing intervals. At short cueing intervals reaction times were longer when
      different peak forces had to be specified than when same peak forces were cued,
      and this reaction-time difference declined as the cueing interval was increased.
      Independent of the cueing interval intermanual correlations of peak forces, rise
      times, and reaction times were smaller in conditions with different peak forces
      than in those with same peak forces. In the second experiment imperative signals
      for left-hand and right-hand contractions were separated in time. Target forces
      for the first response were cued with variable cueing intervals, while for the
      second response the cues were presented simultaneously with the second imperative
      signal. Reaction time of the second response was longer when target forces for
      the two successive responses were different rather than same, and this reaction
      time difference declined when the delay of the second signal was increased as
      well as when the cueing interval for the first response became longer. These
      results are consistent with the hypothesis of a transient cross-talk between
      concurrent processes of peak-force specifications; in addition they indicate
      generalization of the decoupling required to specify different peak forces
      concurrently to the specification of temporal response characteristics and to
      processes of response initiation.

PMID- 12227437
TI  - Expectancy, controlled attention and automatic attention in prospective temporal
      judgments.
AB  - Two experiments indicate that prospective judgments of a temporal target are
      influenced by nontarget temporal features. The basic task was to reproduce a
      target interval marked by visual events. In addition, visual or auditory
      interfering events were delivered. Experiment 1 showed that temporal reproduction
      is shorter when the interfering events occupy a late rather than early position
      during the target interval, a result explained in terms of expectancy, which
      causes attention shifts. This study also revealed that similar trends are
      obtained whether the interfering event involves a specific task or is irrelevant.
      Experiment 2 confirmed the position effect, and showed that the duration of an
      irrelevant cue can influence judgment of the target interval, as if it were also
      timed without appropriate control.

PMID- 12227438
TI  - Self-reported increase in asthma severity after the September 11 attacks on the
      World Trade Center--Manhattaan, New York, 2001.
AB  - Asthma is a chronic condition that affects approximately 14 million persons in
      the United States and is characterized by airway inflammation, reversible airway
      obstruction, and airway hyperresponsiveness to a variety of triggers. Both
      environmental and psychological factors can trigger asthma exacerbations, and a
      seasonal increase in asthma morbidity occurs in the fall. This report summarizes
      the results of a telephone survey conducted among Manhattan residents 5-9 weeks
      following the September 11, 2001, terrorist attacks on the World Trade Center
      (WTC) in lower Manhattan in New York City. The findings indicate that among the
      13% of adult respondents with asthma, 27% reported experiencing more severe
      asthma symptoms after September 11. Although a normal seasonal increase in asthma
      severity was expected, increased severity was reported more commonly among
      asthmatics reporting psychological distress associated with the attacks and/or
      difficulty breathing because of smoke and debris during the attacks. Persons with
      asthma and their clinicians should be aware of the role environmental and
      psychological factors might play in worsening asthma after disasters.

PMID- 12227439
TI  - Psychological and emotional effects of the September 11 attacks on the World
      Trade Center--Connecticut, New Jersey, and New York, 2001.
AB  - To measure the psychological and emotional effects of the September 11, 2001,
      terrorist attacks on the World Trade Center (WTC), Connecticut, New Jersey, and
      New York added a terrorism module to their ongoing Behavioral Risk Factor
      Surveillance System (BRFSS). This report summarizes the results of the survey,
      which suggest widespread psychological and emotional effects in all segments of
      the three states' populations. The findings underscore the importance of
      collaboration among public health professionals to address the physical and
      emotional needs of persons affected by the September 11 attacks.

PMID- 12227440
TI  - Occupational health guidelines for remediation workers at Bacillus anthracis
      contaminated sites--United States, 2001-2002.
AB  - Despite the apparently low disease rate from exposure, protection for remediation
      workers at B. anthracis-contaminated sites is warranted because inhalational
      anthrax is rapidly progressive and highly fatal, PPE does not guarantee 100%
      protection, and the risk for developing disease cannot be characterized
      adequately. The guidelines described here go beyond HAZWOPER requirements and
      include recommendations for treating inhalation exposure to B. anthracis spores
      as a medical emergency, medical follow-up as long as the risk for anthrax
      persists or a worker is receiving antibiotic prophylaxis, accommodation of a
      mobile workforce, and assurance that workers understand the need for immediate
      medical attention should symptoms of anthrax occur. Completion of the 6-dose
      series of anthrax vaccine followed by annual booster doses will decrease the
      reliance on antibiotics for the prevention of anthrax. Measures to protect
      workers must include both medical measures (i.e., vaccination, antibiotic
      prophylaxis, or a combination of both) and measures to prevent exposure (e.g.,
      PPE and environmental controls).

PMID- 12227441
TI  - Protecting building environments from airborne chemical, biologic, or radiologic
      attacks.
AB  - In November 2001, following the discovery that letters containing Bacillus
      anthracis had been mailed to targeted locations in the United States, the
      Secretary of the U.S. Department of Health and Human Services requested site
      assessments of an array of public- and private-sector buildings by a team of
      engineers and scientists from CDC's National Institute for Occupational Safety
      and Health (NIOSH). In November 2001, this team assessed six buildings, including
      a large hospital and medical research facility, a museum, a transportation
      building, two large office buildings, and an office/laboratory building. In
      January 2002, additional building assessments were conducted at CDC campuses in
      Atlanta and, in April 2002, at a large, urban transportation facility. A total of
      59 buildings were evaluated during this 5-month period.

PMID- 12227442
TI  - West Nile virus infection in organ donor and transplant recipients--Georgia and
      Florida, 2002.
AB  - On August 23, 2002, the Georgia Division of Public Health (GDPH) and CDC were
      notified of two cases of unexplained fever and encephalitis in recipients of
      organ transplants from a common donor. An investigation has identified illness in
      two other recipients from the same donor: one with encephalopathy and the other
      with febrile illness. CDC, the Food and Drug Administration, GDPH, and the
      Florida Department of Health are conducting the investigation. This duster could
      possibly represent the first recognized transmission of West Nile virus (WNV) by
      organ donation.

PMID- 12227444
TI  - Kinematic and kinetic gait analysis in the sagittal plane of trans-femoral
      amputees before and after special gait re-education.
AB  - A special gait-training programme, combining a psychological therapeutic approach
      with methods in physiotherapy and body awareness, was used to re-educate nine
      unilateral trans-femoral amputees. All were rehabilitated trauma or tumour
      amputees with an age of 16-60 years. They had worn prostheses for more than 18
      months. The re-education aimed at integrating the prosthesis in normal movements
      and increasing body awareness. Gait was measured before and after treatment and
      at 6 months follow-up with a three-dimensional motion analysis system. Results
      showed almost normalised gait speed and increased symmetry in the hip joints with
      increased muscle work on the amputated side both immediately and at follow-up. At
      follow-up there were significant differences in almost all parameters between the
      two legs of the subjects and when compared to a reference group of 18 healthy
      volunteers of similar age. Thus, the intact leg compensates for loss of function
      in the amputated leg and thereby works differently compared to the reference
      group. For example, during shock absorption the extension moment in the intact
      knee increased from 0.6 Nm/kg before to 1.0 Nm/kg after treatment and at follow
      up compared to 0.4 Nm/kg in the reference group. The eccentric power of
      quadriceps increased from 0.6 w/kg before to 1.8 w/kg after treatment and 1.7
      w/kg at follow-up compared to 0.4 w/kg in the reference group. The limp of
      amputees is usually observed in the frontal plane, but the authors' special focus
      on the sagittal plane here illustrates gait propulsion influences. The positive
      training results remained after six months.

PMID- 12227445
TI  - A post-discharge functional outcome measure for lower limb amputees: test-retest
      reliability with trans-tibial amputees.
AB  - There are approximately 700 lower limb amputations performed throughout Scotland
      each year. A national system of survey and analysis conducted by the Scottish
      Physiotherapy Amputee Research Group (SPARG) provides information on these
      patients up until discharge from hospital. However, there has been no method of
      collecting long-term functional and prosthetic use information following
      discharge. The Functional Measure for Amputees (FMA) has, therefore, been
      developed from the Prosthetic Profile of the Amputee (PPA) questionnaire,
      designed by Gauthier-Gagnon and colleagues in Canada (Grise et al, 1993).
      Modifications to the PPA were carried out to make it more appropriate for the
      Scottish amputee population; these changes were approved by the original authors.
      The test-retest reliability of the 14-question FMA was assessed using a repeat
      postal questionnaire study. One hundred and thirty-three (133) from a possible
      390 trans-tibial amputees were returned. Comparing sociodemographic and clinical
      variables between consenters and non-consenters showed no evidence to support
      sample bias. Continuous data items on the FMA analysed using an intraclass
      correlation coefficient showed ICC values of 0.74, 0.85, 0.96 and 0.64.
      Categorical data items analysed using percentage agreements showed reliability of
      over 70% for seven items, between 40% and 70% for three items and between 20% and
      40% for the remaining three items. The FMA questionnaire was found to be reliable
      on the majority of its questions and moderately reliable on the remaining
      questions during successive follow-up postal administrations.

PMID- 12227446
TI  - Nottingham Health Profile: reliability in a sample of 542 subjects with major
      amputation of one or several limbs.
AB  - The reliability of a generic health-related quality of life measure was assessed
      for subjects with major amputation of one or several limbs. The Nottingham Health
      Profile was sent a first time to 1011 limb amputees, and a second time to the 542
      respondents to the first inquiry. The intraclass correlation coefficient (ICC)
      between the answers to each survey was highest for the categories of distress
      caused by pain (ICC = 0.83), emotional reactions (ICC = 0.83) and mobility (ICC =
      0.81). It was found satisfactory for energy level (ICC = 0.75), sleep (ICC =
      0.75) and social isolation (ICC = 0.64). It is concluded that the NHP is a
      reliable health related quality of life measure for amputees.

PMID- 12227447
TI  - Colourfast pigments in silicone hand and maxillofacial prostheses.
AB  - This study addresses the clinical problem of long-term discolouration of silicone
      hand and maxillofacial prostheses. Seven (7) pigment hues, considered essential
      for achieving a suitable tissue colour-matched prosthesis, were compared for
      their colourfast property, across three selected proprietary formulations. In
      all, a series of 21 pigments, were tested for colourfastness. The pigments,
      presenting as suspensions (PS), pastes (PP) and dry pigments (PD), were exposed,
      over nine months, to ultraviolet light, elevated temperatures and varying
      concentrations of salinity. Colour change of the pigments was measured and
      expressed as Commission International de l'Eclairage (CIE) (L*, a*, b*) units.
      Pigment discoloration was significantly attributed to ultraviolet light.
      Pigmented and clear silicone samples showed a "yellowing" (+delta b*) effect.
      Lighter pigments became darker (-delta L*) in shade. Pigment samples at the
      elevated temperature of 50 degrees C showed significant but small colour change
      (delta E, 0.77 to 3.63). Only the master blue pigment (PS-4) recorded a higher
      delta E, 6.26 at 50 degrees C. At a moderate temperature of 35 degrees C, both
      pigmented and clear silicone test samples remained relatively colourfast.
      Comparison was made to control samples, stored in darkness, at 26 degrees C. The
      pigments were generally colourfast (deltaE<6 units) to saline solutions of 0.15 M
      and 5.0 M concentrations. Only the monastral red (PD-3) pigment recorded a delta
      E of 9.33, in 0.15 M normal saline, simulating the vulnerability of this pigment
      to the salinity of human sweat. Pigment hues were systematically ranked according
      to colourfastness. Pigment suspensions were more colourfast than pigment pastes.

PMID- 12227448
TI  - Throwing down the gauntlet: 'iron hands' and the sixteenth century armourer.
AB  - The work of sixteenth century 'medical armourers' in the manufacture of iron
      hands based on skills developed in the manufacture of armoured gauntlets is
      briefly explored. In order to illustrate their form and function, reference is
      made to an iron hand in the collection of the British Museum and a comparison is
      made with another example manufactured around the same period.

PMID- 12227449
TI  - Effect of using prismatic eye lenses on the posture of patients with adolescent
      idiopathic scoliosis measured by 3-d motion analysis.
AB  - This is a preliminary investigation to detect the body sway and postural changes
      of patients with AIS under different spatial images. Two pairs of low-power
      prismatic eye lenses (Fresnel prisms) with 5 dioptre and 10 dioptre were used. In
      the experiment, the apices of the prisms were orientated randomly at every 22.5
      degrees from 0 degrees to 360 degrees to test changes. Four patients with mean
      age of 11 and Cobb's angle of 30 degrees were recruited and the results showed
      that the low-power prisms at specific orientations (157.5 degrees and 180
      degrees) could cause positive postural changes (2.1 degrees-2.7 degrees reduction
      of angle of trunk mis-alignment) measured by 3-D motion analysis. This might be
      used for controlling their scoliotic curves by induced visual bio-feedback. Apart
      from this laboratory test, a longitudinal study is necessary to investigate the
      long-term effect of the prisms at different powers and orientations (under both
      static and dynamic situations) on the patient's posture, spinal muscular
      activities, vision, eye-hand coordination, psychological state and other daily
      activities before it becomes an alternative management of AIS.

PMID- 12227450
TI  - Using NetMeeting for remote configuration of the Otto Bock C-Leg: technical
      considerations.
AB  - Telehealth has the potential to be a valuable tool for technical and clinical
      support of computer controlled prosthetic devices. This pilot study examined the
      use of Internet-based, desktop video conferencing for remote configuration of the
      Otto Bock C-Leg. Laboratory tests involved connecting two computers running
      Microsoft NetMeeting over a local area network (IP protocol). Over 56 Kbs(-1),
      DSL/Cable, and 10 Mbs(-1) LAN speeds, a prosthetist remotely configured a user's
      C-Leg by using Application Sharing, Live Video, and Live Audio. A similar test
      between sites in Ottawa and Toronto, Canada was limited by the notebook
      computer's 28 Kbs(-1) modem. At the 28 Kbs(-1) Internet-connection speed,
      NetMeeting's application sharing feature was not able to update the remote
      Sliders window fast enough to display peak toe loads and peak knee angles. These
      results support the use of NetMeeting as an accessible and cost-effective tool
      for remote C-Leg configuration, provided that sufficient Internet data transfer
      speed is available.

PMID- 12227451
TI  - A new trim line concept for trans-tibial amputation prosthetic sockets.

PMID- 12227452
TI  - Evaluation of safety and reliability in an infant reciprocal walking orthosis.
AB  - In response to new demands for infant walking orthoses consideration was given to
      the development of a device for this category of patient. A specially developed
      hip joint with the required structural properties (Woollam et al., 2001) provided
      an opportunity for this development. Earlier structural assessment, and limited
      cyclic load testing of key elements of the orthosis (primarily the body brace),
      confirmed that a safe device for evaluation with patients could, theoretically,
      be produced. A provisional prototype was therefore designed and manufactured for
      initial structural testing of the complete infant orthosis (Stallard et al.,
      2001). Efficiency of walking is strongly influenced by the lateral rigidity of
      the orthosis. Monitoring the structural performance of the provisional infant
      design indicated it would equal or improve on the stiffness of that achieved in
      the adult specification. Additionally, relative strength was comparable with the
      adult version, which has proven to be safe and reliable in many years of routine
      prescription. This, together with the limited cyclic testing of the complete
      orthosis (Stallard et al., 2001), gave confidence that it was safe to proceed
      with controlled field evaluation of the infant design when supplied as a
      rehabilitation engineering device within the provisions of an ISO9001 and EN46001
      QA System. This additional study of controlled patient use, and further
      representative cyclic load testing in parallel with the field evaluation, had
      established the long-term structural safety of the orthosis. Wider application is
      now to be introduced through completion of the EC (European Community) Medical
      Devices Directive formalities.

PMID- 12227453
TI  - The ISPO system for cerebral palsy treatment recording (SCePTRe).

PMID- 12227454
TI  - Clinical field-testing of ATLAS prosthetic system for trans-tibial amputees.
AB  - The ATLAS prosthetic system was tested on 81 trans-tibial amputees in two
      tropical areas and followed for about two years. At the conclusion 19% (15/81)
      had given up its use; mostly because of unsatisfactory socket fit, but in 7%
      (6/81) system related failures were the cause of non-compliance; mostly because
      of a shrieking noise from the shin-foot piece during use. System related failures
      were encountered in 62% (41/66) of users; the most serious threat to patient
      safety was fractures of the shank in 39% (26/66) and badly worn feet in 12%
      (8/66). With a failure rate of about 41% after one and a half years the ATLAS
      system is considered unacceptable for general use in trans-tibial amputees.

PMID- 12227455
TI  - Experience in prosthetic supply of patients with lower limb amputations in
      Croatia.
AB  - This study analyses some demographic characteristics of the amputees in Croatia,
      reason and level of amputation, care the amputees receive, the first prosthetic
      supply and functional level after rehabilitation. Anonymised data on all amputees
      in the Clinical Institute for Rehabilitation and Orthopaedic Aids in Zagreb (a
      national centre) were collected during the year 2000. Follow-up was undertaken
      for one year. As a result, the authors analysed 221 patients, classified into 3
      groups according to the level of amputations: trans-tibial, except foot (TT),
      trans-femoral (TF) and bilateral amputations (bilateral). Among the population
      there were: 76% men and 24% women with average age of about 62 years (the average
      age of women was 8 years more than men). The most common diseases that resulted
      in amputation were: diabetes mellitus (DM) 48.9%; obstructive vascular diseases
      (OD): occlusive peripheral arterial disease, Buerger's disease and
      atherosclerosis 27.1%; trauma 11.3%; both OD and DM 7.2%; osteomyelitis (OM) 3.2%
      and tumours (TM) 2.3%. Average period from the amputation to admission for
      prosthetic supply was over 190 days but the average period from admission to
      discharge from the Institute was about 40 days. Prosthetic supply was accompanied
      by certain complications: flexion contractures of neighbouring joints, knee 37.9%
      and hip 35.2%; local complications of soft tissues: necrosis, wound dehiscence,
      soft tissue surplus, ischaemic tissue damage (the most frequent in TT amputation
      35.9%) and phantom pain (55.7% of patients). Hours of daily use of the prosthesis
      at discharge was about 5 hours. Greater independence in fitting and removing the
      prosthesis was observed in patients with TT amputation (86.4%). In conclusion, it
      can be said that the time between the amputation and the beginning of the
      prosthetic supply, mobility at the time of admission, frequency of general and
      local complications and number of days in prosthetic supply, are very important
      for the result of rehabilitation.

PMID- 12227456
TI  - Intestinal function in glycogen storage disease type I.
AB  - Glycogen storage disease type I (GSD I) (McKusick 232200) is caused by inherited
      defects of the glucose-6-phosphatase complex. Patients with GSD Ia as well as
      patients with GSD lb may suffer from intermittent diarrhoea, which seems to
      worsen with age. The cause of this diarrhoea is unknown. This study describes the
      results of investigations of intestinal functions and morphology in patients with
      GSD Ia and GSD lb, which were performed to detect a common cause for chronic
      diarrhoea in GSD I. The following were investigated: faecal fat excretion, faecal
      alpha1-antitrypsin and faecal chymotrypsin, expiratory H2 concentrations,
      persorption of cornstarch in urine and colonic biopsies. With the investigations
      presented in this study, no common cause for diarrhoea in GSD I was found. In GSD
      lb loss of mucosal barrier function due to inflammation, documented by increased
      faecal alpha1-antitrypsin excretion (3.5-9.6 mg/g dry faeces) and inflammation in
      the colonic biopsies, seems to be the main cause. The inflammation is most likely
      related to disturbed neutrophil function, which is often found in GSD lb. Whether
      another cause is involved in GSD Ia and in GSD Ib, related to the disturbed
      function of glucose-6-phosphatase in the enterocyte, remains to be investigated.

PMID- 12227457
TI  - Cardiac involvement in Wilson disease.
AB  - BACKGROUND: Wilson disease is an inherited autosomal recessive disorder of copper
      metabolism resulting in pathological accumulation of copper in the liver, brain
      and other tissues. One of the reported manifestations is cardiac involvement.
      METHODS: We studied 42 patients with Wilson disease (19 men and 23 women, mean
      age 34 +/- 10 y) and 42 age- and sex-matched healthy volunteers. All subjects
      underwent complete echocardiographic examination; 24 h ECG Holter monitoring was
      performed in 23 Wilson disease patients. RESULTS: In comparison to healthy
      subjects, patients with Wilson disease had increased thickness of the
      interventricular septum (9.5 +/- 1.4 vs 8.6+/-1.1 mm, p < 0.01) and left
      ventriclular (LV) posterior wall (9.1 +/- 1.3 vs 8.2 +/- 1.0 mm, p < 0.01). While
      the two groups did not differ in LV mass index, relative LV wall thickness was
      significantly increased in Wilson disease patients compared to control subjects
      (0.39 +/- 0.06 vs 0.34 +/- 0.04 p < 0.001). Concentric LV remodelling was present
      in 9 patients (21%) and LV hypertrophy in one patient. Systolic LV function
      showed a nonsignificant trend towards lower values in Wilson disease patients (EF
      62 +/- 5% vs 64 +/- 50%, p = 0.06). Diastolic filling and the frequency of
      valvular abnormalities were comparable in both groups. The established
      echocardiographic abnormalities did not correlate with the type of Wilson disease
      manifestation, the presence of the His1069Gln mutation, laboratory parameters or
      the duration and type of therapy. Twenty-four-hour ECG Holter monitoring detected
      ECG abnormalities in 10 patients (42%), the most frequent findings being runs of
      supraventricular tachycardias and frequent supraventricular ectopic beats.
      CONCLUSIONS: Cardiac involvement in Wilson disease patients was mild,
      characterized by LV parietal thickening with an increased prevalence of
      concentric LV remodelling and a relatively high frequency of benign
      supraventricular tachycardias and extrasystolic beats.

PMID- 12227458
TI  - A molecular, enzymatic and clinical study in a family with hereditary
      coproporphyria.
AB  - A 30-year-old woman suffered from acute crises with abdominal, neurological and
      psychiatric complaints. Urinary haem precursors and faecal porphyrins were
      excessively elevated compared to the upper level of the normal range. Urinary
      coproporphyrin isomer III was increased and faecal coproporphyrin isomers I and
      III showed a complete inversion of the normal ratio. Thus, hereditary
      coproporphyria was diagnosed in this woman. The father, one brother and a sister
      were shown to be gene carriers of hereditary coproporphyria by their urinary and
      faecal excretory constellations. The excretory patterns of the mother and a
      second brother were normal. Coproporphyrinogen oxidase activity was decreased to
      49% and 58%, in the patient and her father, respectively. The mother's enzyme
      activity was normal (98%). Coproporphyrinogen oxidase concentration was enhanced
      1.8-fold and 2.7-fold in the patient and her father, respectively. Mutation
      analysis revealed the insertion of an adenine at position 857 in exon 4 of the
      coproporphyrinogen oxidase gene. The gene defect was confirmed by denaturing
      gradient gel electrophoresis in the patient and her father. The patient was
      treated by intravenous interval therapy with haem arginate for 10 months, with
      good clinical and metabolic response.

PMID- 12227459
TI  - Neurotransmitter metabolites in CSF: an external quality control scheme.
AB  - We report an international external quality control scheme on neurotransmitter
      metabolites in cerebrospinal fluid (CSF). The neurotransmitter metabolites
      homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4
      hydroxyphenylglycol (MHPG) are analysed to diagnose inborn errors of
      neurotransmitter metabolism. HVA is the catabolite of dopamine; 5-HIAA is the
      catabolite of serotonin; and MHPG is the catabolite of noradrenaline. In the
      first phase, 12 laboratories from six countries participated in this special
      quality control scheme to define the present state of the art and achieve
      harmonization in analytical outcome and interpretation. In the second part,
      recoveries, dilutions and methods for sample preparation were compared. The
      results of 3 of 12 laboratories were excluded because of unacceptable
      intralaboratory coefficients of variations (CV) for HVA and/or 5-HIAA. The inter-
      and intralaboratory CVs, the linearity and the recovery were acceptable for the
      other laboratories for both parameters. Unacceptable differences in the reference
      ranges between laboratories, leading to differences in interpretation of the
      results, became obvious. There was a significant improvement of the
      interlaboratory CV for HVA after standardization with a calibrator. The
      reproducibility of MHPG measurement appeared to be adequately established in only
      two laboratories and recovery was low in all five measuring this metabolite. The
      quality control scheme is an invaluable tool for controlling the analytical
      outcome and providing support to laboratories to improve their quality.

PMID- 12227460
TI  - Reproductive fitness in maternal homocystinuria due to cystathionine beta
      synthase deficiency.
AB  - Early diagnosis and improved treatment are leading to the potential for increased
      reproductive capability in homocystinuria due to cystathionine beta-synthase
      (CbetaS) deficiency, but information about reproductive outcome and risk of
      thromboembolism in pregnancy is limited. To provide further information, clinical
      and biochemical information was obtained on women with maternal homocystinuria,
      on their pregnancies and on the offspring. This information included blood
      sulphur amino acids and total homocysteine, CbetaS gene mutations and
      developmental and cognitive scores in the offspring. The study involved 15
      pregnancies in 11 women, of whom 5 were pyridoxine-nonresponsive and 6 were
      pyridoxine-responsive. Complications of pregnancy included pre-eclampsia at term
      in two pregnancies and superficial venous thrombosis of the leg in a third
      pregnancy. One pregnancy was terminated and two pregnancies resulted in first
      trimester spontaneous abortions. The remaining 12 pregnancies produced live-born
      infants with normal or above-normal birth measurements. One offspring has
      multiple congenital anomalies that include colobomas of the iris and choroid,
      neural tube defect and undescended testes. He is also mentally retarded and
      autistic. A second offspring has Beckwith-Wiedemann syndrome. The remaining 10
      offspring were normal at birth and have remained normal. There was no
      relationship between the severity of the biochemical abnormalities or the
      therapies during pregnancy to either the pregnancy complications or the offspring
      outcomes. The infrequent occurrences of pregnancy complications, offspring
      abnormalities and maternal thromboembolic events in this series suggest that
      pregnancy and outcome in maternal homocystinuria are usually normal.
      Nevertheless, a cautious approach would include careful monitoring of these
      pregnancies with attention to metabolic therapy and possibly anticoagulation.

PMID- 12227461
TI  - Very long-chain acyl-CoA dehydrogenase deficiency in an infant presenting with
      massive hepatomegaly.
AB  - A 9-month-old boy with presented generalised hypotonia, severe cardiomyopathy,
      and massive liver enlargement following 10 days of viral gastroenteritis. He was
      diagnosed with very long-chain acyl-CoA dehydrogenase deficiency and has been
      successfully treated.

PMID- 12227462
TI  - Pregnancy and tyrosinaemia type II.
AB  - A female patient with tyrosinaemia type II is reported having undergone two
      untreated pregnancies. During pregnancies, plasma tyrosine was raised. The
      outcomes of both offspring show that maternal tyrosinaemia may have an adverse
      effect on the developing fetus.

PMID- 12227463
TI  - Sandhoff disease in a golden retriever dog.
AB  - A golden retriever dog is described with total hexosaminidase deficiency and
      raised GM2-ganglioside in CSF. The animal represents a model for human Sandhoff
      disease.

PMID- 12227464
TI  - Tetrahydrobiopterin responsiveness in a large series of phenylketonuria patients.
AB  - In a group of 87 consecutive patients with hyperphenylalaninaemia born since
      1990, only 3 patients showed a (temporary) decrease of serum phenylalanine levels
      after tetrahydrobiopterin (BH4) loading in usual doses (20 mg/kg body weight).

PMID- 12227465
TI  - Sequence analysis of Hungarian LHON patients not carrying the common primary
      mutations.
AB  - We describe sequence analysis of the mitochondrial DNA of five Hungarian patients
      diagnosed with probable LHON, who do not carry any of the three primary point
      mutations. We report three novel mutations, one of which might have a pathogenic
      role.

PMID- 12227466
TI  - A novel Y243S mutation in the pyruvate dehydrogenase El alpha gene subunit:
      correlation with thiamine pyrophosphate interaction.
AB  - We identified a new Y243S mutation in the X-linked E1 alpha-PDH gene in a patient
      with pyruvate dehydrogenase complex (PDHc) deficiency. The activity in cultured
      fibroblasts was very low even in the presence of high thiamine pyrophosphate
      (TPP) concentrations, indicating that the defect could be due to decreased
      affinity of PDHc for TPP.

PMID- 12227467
TI  - Two new mutations in children affected by partial biotinidase deficiency
      ascertained by newborn screening.
AB  - Mutation analysis performed on DNA from 6 Italian patients with partial
      biotinidase deficiency ascertained by newborn screening allowed the
      identification of two new mutations, c1211C > T (T404I) and a single base
      deletion c594delC. All patients were compound heterozygous for the D444H amino
      acid substitution showing that this mutation is also common in Italian patients
      affected by partial biotinidase deficiency.

PMID- 12227468
TI  - Effect of medetomidine-butorphanol-ketamine anaesthesia and atipamezole on heart
      and respiratory rate and cloacal temperature of domestic pigeons.
AB  - The purpose of this study was to evaluate the sedative-anaesthetic effects of a
      combination of medetomidine (M, 50 microg per pigeon), butorphanol (B, 50 microg
      per pigeon) and ketamine (K, 25 mg per pigeon) in domestic pigeons. Eight
      domestic pigeons (four male and four female, 8-15 months old) were used. The
      combination of Medetomidine and butorphanol injectable solutions were used to
      produce sedation. Ten minutes after M + B administration, K was injected. The
      anaesthetic effects of the drugs were reversed by administration of Atipamazole
      (AT) at 60 min after K administration. All drugs were injected into the pectoral
      muscles. The sedative-anaesthetic effects of the M + B-K combination and,
      alterations in respiratory rate (RR), heart rate (HR), electrocardiographic (ECG)
      findings and cloacal temperature (CT) were investigated before and 10 min after
      pre-medication with M + B, at 5, 15, 30, 45 and 60 min during the onset of K
      anaesthesia and at 1, 5, 10, 20, 30 and 60 min following the administration of
      AT. The HR and RR of pigeons decreased within 10 min following M + B
      administration and remained lower until 1st and 5 min of AT injection,
      respectively. In ECG, no significant alterations in P, Q, R and S-values were
      observed, however, arhythmia was recorded for three pigeons, which returned to
      normal values following AT administration throughout the measurement. Cloacal
      temperature decreased gradually during the anaesthesia from 41.0 to 32.7 degrees
      C. The drug combination used in this study produced a satisfactory general
      anaesthesia for seven of the eight pigeons. All pigeons were unconscious within 5
      min after K administration as indicated by disappearance of the palpebral and
      corneal reflexes and lack of reaction to the pain stimuli during the study. The
      effect of AT administration was observed within 10 min as all pigeons responded
      partly against stimuli and all reflexes. It is concluded that M + B-K anaesthesia
      in pigeons is a safe and reliable anaesthetic protocol for surgery.

PMID- 12227469
TI  - Effect of short-term hypothermia on lipid peroxidation and antioxidant enzyme
      activity in rats.
AB  - This experiment was carried out to determine the effect of short-term hypothermia
      on blood malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px) and glucose-6-phosphate dehydrogenase (G-6-PD)
      concentrations in rats. Twenty Sprague-Dawley rats were used weighing 180-200 g
      and on average 3.5 months old. They were randomly divided into two experimental
      groups: control (without cooling) and hypothermic (with cooling). The rats of the
      hypothermic group were cooled by immersion into cold water (10-12 degrees C), and
      the control rats were immersed into water of body temperature (37 degrees C) up
      to the neck without using any anaesthetic or tranquilizer for 3 min Rectal body
      temperatures of both groups were measured and blood samples to analyse MDA, GSH,
      SOD, GSH, GSH-Px and G-6-PD were collected immediately after the treatment. It
      was found that the MDA level was higher and the GSH and G-6-PD levels were lower
      in the hypothermic group than those in the controls. There was no difference
      between the control or hypothermic group regarding SOD or GSH-Px levels. It is
      concluded that acute hypothermia increased the lipid peroxidation and decreased
      the GSH and G-6-PD levels in rats.

PMID- 12227470
TI  - A direct StyI polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) test for the myophosphorylase mutation in cattle.
AB  - Myophosphorylase deficiency in cattle is a muscle disease induced by a C-->T
      point mutation in codon 489 of the myophosphorylase gene, which until now has
      only been diagnosed in the Charolais breed. The disease seems to be inherited in
      an autosomal monogenic recessive manner. A calf of double muscled phenotype was
      suspected of suffering from myophosphorylase deficiency based on typical
      symptoms, i.e. brown-coloured, transparent urine, occurring after exercise;
      exercise intolerance; symptoms of pain; and an elevated level of plasma creatine
      kinase. The presence of the previously described mutation was excluded using a
      newly developed, improved polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) procedure to identify easily heterozygous carriers and
      homozygous affected animals.

PMID- 12227471
TI  - Flow cytometric testing of immunological effects of a phytomedicinal combination
      (equimun) and its compounds on bovine leucocytes.
AB  - One of the major goals of this study was to establish fast, reliable and
      sensitive assays for the quality control of immunomodulating phytopreparations
      and to determine whether pharmacological compounds or phytopreparations have
      effects on bovine immune cells. Flow cytometric methods were chosen because they
      are very sensitive in the detection of even subtle effects on cells. In this
      study, we addressed the question of whether these methods are useful in
      monitoring the effects of EquiMun and its compounds on bovine leucocytes in
      vitro. EquiMun is a fixed combination of Echinacea purpurea (Ec), Thuja
      occidentalis (Th) and elemental phosphorus (Ph) in different starting
      concentrations. Separated blood mononuclear cells (MNC) and polymorphonuclear
      cells (PMN, mainly neutrophils) were cultured for up to 44 h in vitro in the
      presence or absence of the tested substances. Whereas MNC were not affected by
      any of the compounds, EquiMun, Ec, Th and Ph significantly reduced the forward
      scatter (size) of cultured PMN without affecting their side scatter
      (granularity). The size effects were paralleled by a significantly enhanced
      viability of PMN after 20 h in culture. The observed effects were constant over
      wide concentration ranges and indicate a very similar reaction of leucocytes from
      individual cows. Whereas spontaneous generation of reactive oxygen species (ROS)
      by neutrophils was up-regulated by Ph and EquiMun, EquiMun down-regulated the
      phorbol ester-stimulated ROS production. However, ROS generation by neutrophils
      displayed a large inter-individual variation with less apparent, down-regulatory
      effects of EquiMun. The ability of PMN to kill target cells via antibody
      independent cellular cytotoxicity showed small inter-individual variations and
      was enhanced by Ec and Th but not by Ph and EquiMun, probably due to dose
      dependent effects. In summary, the flow cytometric characterization of cellular
      viability and shape changes of neutrophils seem to be a suitable and reliable
      approach for the quality test of immunomodulating phytomedicines based on
      bioassays.

PMID- 12227472
TI  - Ultrasonographic evaluation of reticular motility in cows after administration of
      atropine, scopolamine and xylazine.
AB  - The goal of this study was to evaluate the effect of various dosages and routes
      of administration of atropine, scopolamine and xylazine on reticular motility in
      cows. Groups of five cows received atropine, scopolamine or xylazine at dosages
      varying from 0.01 to 0.20 mg/kg. The drugs were administered intramuscularly and
      intravenously; atropine was also given subcutaneously. A total of 17 trials, each
      using five cows, were carried out. Reticular motility was assessed for 3 min
      immediately prior to the administration of a drug and for 21 min after
      administration, and the latter period was divided into seven 3-min intervals. The
      motility was further assessed during 3-min periods every 10 min starting 28 min
      and ending 141 min after administration of a drug. During each 3-min interval,
      the number of reticular contractions or the occurrence of reticular atony was
      determined. Onset and duration of reticular atony were assessed. All three drugs
      inhibited reticular motility but onset varied with route of administration and
      dosage. As expected, the onset of reticular atony occurred most rapidly after
      intravenous administration of each drug, followed by intramuscular and
      subcutaneous administration. Reticular atony occurred 0-3.0 min after the
      intravenous administration of each drug and at all dosages except the lowest
      dosage of atropine. Atony lasted for 3-111 min. Reticular atony occurred 3-18 min
      and 9-15 min after intramuscular and subcutaneous administration, respectively.
      It lasted 32-108 min and 39-122 min for the intramuscular and subcutaneous
      routes, respectively. For each drug, higher dosages resulted in a more rapid
      onset and longer duration of reticular atony than did lower dosages. This study
      demonstrated that administration of atropine, scopolamine and xylazine results in
      reticular atony. Whether this has clinical relevance requires further
      investigation.

PMID- 12227473
TI  - Cytometric evaluation of peripheral blood lymphocytes in dogs with lymphoma
      during chemotherapy.
AB  - Twenty dogs with clinically diagnosed multicentric lymphoma were evaluated for
      percentages of peripheral blood lymphocyte subpopulations. Cytometric analysis
      was performed before and during chemotherapy. The results were compared to those
      obtained from a control group of healthy dogs. The percentages of CD5+, CD4+ and
      CD8+ cells were markedly decreased and CD21-like+ cells markedly increased in
      dogs with lymphoma in comparison with the control group. During the course of
      chemotherapy these values returned to ranges observed in healthy animals.

PMID- 12227474
TI  - Clinico-pathological aspects of canine cutaneous and mucocutaneous plasmacytomas.
AB  - In this study the clinico-pathological aspects of cutaneous and mucocutaneous
      plasmacytomas were investigated in 63 dogs (one dog with two tumours). The
      tumours were most commonly observed in the skin of the trunk and legs. Yorkshire
      Terrier (n = 8) was the most commonly affected breed and males were affected more
      commonly than females (36 versus 23, respectively). Plasmacytomas were
      histologically classified into mature, hyaline, cleaved, asynchronous,
      monomorphous blastic and polymorphous blastic cell types. Monomorphous blastic
      cell type was the most frequent type (n = 21), followed by cleaved (n = 19) and
      asynchronous (n = 11) cell types. Secondary amyloid depositions were observed in
      eight cases. Immunohistochemical staining showed monoclonal lambda light chain
      positivity in all cases. In the immunohistochemical staining for cyclin D1, which
      is a prognostic marker in human plasma cell tumours, moderate numbers of positive
      tumour cells were observed in only one case of (muco)cutaneous plasmacytoma. All
      other cases were negative or contained few positive tumour cells. On the other
      hand, high numbers of tumorous plasma cells reacted positively with cyclin D1 in
      three out of six cases of canine multiple myelomas. Prognosis of the
      (muco)cutaneous plasmacytomas was good, except in one dog which developed a
      lymphoma afterwards. No significant correlations were observed between the cell
      type and the location of the tumour, presence of amyloid or prognosis.

PMID- 12227475
TI  - Characteristics and cholinergic control of the 'minute rhythm' in ovine antrum,
      small bowel and gallbladder.
AB  - Eight adult conscious rams were used to characterize further the minute rhythm
      and to determine the role of cholinergic receptors in nervous control of this
      event. In chronic experiments, the myoelectrical and motor activity of the
      gastrointestinal tract and gallbladder were recorded. Physiological experiments
      were performed in fasted or non-fasted rams before, during and after feeding, and
      the occurrence of minute rhythm during various phases of the migrating motor
      myoelectric complex was observed. The pattern occurred most frequently in the
      small intestine, where it exhibited mostly the propagating character. It was also
      detectable in the ileum. In the gallbladder, the minute rhythm arrived
      systematically and its character was irregular, propagating, retropropagating or
      stationary. In all episodes observed, it was well correlated with that in the
      small intestine. In the pyloric antrum, the minute rhythm was identified
      occasionally. During pharmacological experiments, 0.15 M NaCl or graded doses of
      hexamethonium, atropine and pirenzepine were administered intravenously during
      various phases of the migrating motor myoelectric complex, in fasted and non
      fasted animals, before and during feeding. The drugs inhibited the minute rhythm
      in the small bowel for a longer period than in the gallbladder. However, the
      smallest dose of pirenzepine (0.02 mg/kg) exerted a non-significant effect both
      in the small intestine and in the gallbladder. It is concluded, that in normal
      conditions the minute rhythm occurs regularly in the entire small intestine and
      in the gallbladder. In the small intestine the pattern is organized more
      precisely. The minute rhythm is controlled by nicotinic receptors and by
      muscarinic receptor subtypes.

PMID- 12227476
TI  - A preliminary study on the effect of ultrasound therapy on the healing of
      surgically severed achilles tendons in five dogs.
AB  - This study was conducted on the left Achilles tendon in five clinically normal
      dogs. The Achilles tendon was surgically exposed and severed 3-4 cm proximal to
      the point of its insertion. Tenorrhaphy was undertaken by the application of
      three sutures on the various tendon units of the Achilles tendon using single
      locking-loop sutures with polyamide no. 1-0. The superficial digital flexor
      tendon was sutured with catgut using two horizontal mattress sutures. No
      ultrasound therapy was used in the animals of group I (control). Ultrasound
      therapy was given to the animals of group II (treated) starting from the third
      day post-operatively at 0.5 W/cm2 for 10 min daily for 10 days. A cortical screw
      was used for immobilization of the tibiotarsal joint which was removed 4 weeks
      after tenorrhaphy. Post-operatively, healing of the Achilles tendon was monitored
      using clinical observations, ultrasonography, gross and histomorphological
      observations at various intervals up to 120 days in both groups. Clinically, the
      dogs showed significant lameness for the first 4-5 days, which disappeared
      earlier in the ultrasound-treated (group II) animals than the controls (group I).
      Extension and flexion of the hock joint were found to be near normal at 6 weeks
      after the repair of the Achilles tendon. Ultrasonography showed anechoic to hypo
      echoic echo-texture on days 3 and 7 after repair. By day 40, the echo-texture
      started to improve to hypo-echoic in group II, but in group I anechoic areas were
      still observed. However, the tendon showed near normal mottled hypo- to hyper
      echoic texture in both groups by day 120. Gross observations suggested that the
      Achilles tendon in group II showed comparatively fewer adhesions than in group I
      animals. Histologically, in group II (treated), on day 40, the union was
      comparatively better without any inflammatory reaction. Bundle formation had
      begun in the ultrasound-treated animals which was not observed in the control
      animals. By day 90, more compact parallel bundle formation had taken place with
      minimum cellularity. Bundle formation was in its advanced stage in the treated
      animals. By day 120, the tendon tissue was comparatively acellular and looking
      like a normal tendon. The use of the cortical screw provided good immobilization
      and ultrasound therapy at 0.5 W/cm2 enhanced the Achilles tendon healing in dogs.

PMID- 12227477
TI  - Digoxin- and monensin-induced changes of intracellular Ca2+ concentration in
      isolated guinea-pig ventricular myocyte.
AB  - This study was undertaken to determine the possible mechanisms of actions of
      monensin and digoxin by using isolated guinea-pig ventricular myocytes. Since
      Ca2+ is the major signal for triggering contraction of cardiac muscle, the
      objective of this study was to determine whether monensin and digoxin affect the
      [Ca2+]i of cardiac myocytes and if so is this effect due to an increase in
      [Na+]i. Three different concentrations of digoxin (0.3, 1 and 3 micromol/l) and
      three different concentrations of monensin (0.3, 1 and 3 micromol/l) were used.
      Each treatment was monitored for two hours by using computerized fluoroscopy.
      Both digoxin and monensin increased the [Ca2+]i and accelerated the onset time of
      [Ca2+]i increase in a dose-dependent manner. Normal myocytes (loaded with fura-2
      for 30 min before the treatment) were also compared with 'weakened' myocytes
      (loaded with fura-2 for 3 h before the treatment to create a 'weakened'
      condition). It was found that although 0.3 micromol/l monensin and digoxin did
      not change the [Ca2+]i in normal myocytes, they increased the [Ca2 +]i in
      'weakened' myocytes. Finally, a Na+-free medium was used to demonstrate the
      effect of [Na+]o on both monensin- and digoxin-induced increases in [Ca2+]i. It
      was found that digoxin did not increase the [Ca2+]i in the Na+-free medium.
      Although monensin increased the [Ca2+]i in the Na+-free solution, this increase
      was not as large as in the Na+-containing medium. The results of the study led to
      the conclusion that the positive inotropic effect of digoxin depends on [Na+]o.
      However, monensin increases [Ca2+]i in Na+-dependent and -independent ways. An
      addition conclusion was that 'weakened' myocytes are more sensitive to the
      monensin and digoxin treatment than normal myocytes.

PMID- 12227479
TI  - Immediate and delayed-type reactions in caterpillar dermatitis.
AB  - The mechanism of dermatitis induced by Euproctis caterpillars has not been fully
      clarified, although mechanical stimulation by the spicules as well as chemical
      irritation by venomous components from spicules have been suggested to be
      involved. In this study, skin tests using venomous spicules and the venomous
      extract from the caterpillar of E. pseudoconspersa were carried out on a subject.
      The test site developed both immediate and delayed-type reactions. Next, the
      crude extract was separated into 8 fractions (No. 1-8) using gel filtration HPLC,
      and a skin test using each fraction was performed in the same subject. The result
      showed that only fraction No. 3 caused reactions similar to those in crude venom
      extract. Then skin tests using the crude venom and fraction No. 3 were performed
      in 10 healthy volunteers. The skin reaction caused by crude venom was similar to
      that caused by fraction No. 3 in each subject. Two volunteers showed neither
      immediate nor delayed-type reactions, 4 volunteers showed a delayed-type
      reaction, and the other 4 showed both immediate and delayed-type reactions. These
      results indicate that allergic reactions against venom released by the spicules
      play a role in the induction of dermatitis by E. pseudoconspersa caterpillars.
      Variations in the clinical course of individual patients may be attributable to
      differences in the state of sensitization to the venomous components.

PMID- 12227478
TI  - Transferring and distributing profiles of p,p'-(DDT) in egg-forming tissues and
      eggs of laying hens following a single oral administration.
AB  - Laying hens were administered orally with a single dose of p,p'-(DDT) (1 mg/kg
      bodyweight). The concentrations (microg/g) of DDT or its metabolites, p,p'-(DDE)
      and p,p'-(DDD), in the main tissues involved in egg formation (blood, liver,
      ovary, and oviducts) and egg yolk, collected 1 day after DDT dosing, were
      determined by normal-phase high-performance liquid chromatography. The limits of
      detection were 0.04 microg/g for DDT, 0.07 microg/g for DDE and 0.06 microg/g for
      DDD. In extractable fats from the above tissues and egg yolk, DDT and DDE were
      transferred/distributed throughout the tissues and egg yolk. DDD was detected
      only in the liver. The findings indicate that DDT is metabolized instantaneously
      to DDE/ DDD in the hen's body and they are transferred rapidly into the egg
      forming tissues and egg yolk. Among the four tissues and yolk fats examined, the
      DDT levels were high in the ovary, oviduct and egg yolk; the DDE levels were high
      in the liver, ovary and oviduct and lowest in the yolk (P < 0.01).

PMID- 12227480
TI  - Clinical manifestations of hand eczema compared by etiologic classification and
      irritation reactivity to SLS.
AB  - Hand eczema is a common skin disease. Because of its variable etiologies and
      clinical manifestations, it is difficult to determine the etiology from the
      clinical manifestation. Among the contact allergens, nickel is the most common.
      Patients with hand eczema and a nickel allergy have a poorer prognosis than
      patients without a nickel allergy. The reason is still uncertain; suggestions
      include persistent exposure to nickel or a weak skin barrier. The purpose of our
      study was to identify the characteristic clinical manifestations by etiology and
      to compare the skin barrier state between patients with nickel allergies and
      those without them. Ninety-three patients were classified into 4 types;
      irritation contact type, allergic contact type, atopic type and mixed type. After
      the sodium lauryl sulfate (SLS) test to compare the skin barrier state, visual
      score and transepidermal water loss (TEWL) were measured and analyzed
      statistically. From this study, it was not possible to ascertain a statistical
      difference, however a few characteristic clinical manifestations according to
      etiology can be stated. There was no difference in the visual scoring system or
      the TEWL after the SLS irritation test between the nickel-allergy group and the
      non-allergy group. Therefore, we believe that the poor prognosis of hand eczema
      with nickel allergy may be due to the nickel allergy itself rather than skin
      barrier state.

PMID- 12227481
TI  - Seasonal variation in acne vulgaris--myth or reality.
AB  - A traditional opinion proposed by Western dermatologists is that acne improves in
      summer and worsens in winter. We studied 452 patiens with acne vulgaris and asked
      them about seasonal variation in their acne. A total of 229 patients (50.67%)
      complained of a seasonal variation; a significant proportion (56.33%) noticed an
      aggravation in summer, while 16.16% improved in summer and only 11.35% worsened
      in winter. Apparently winters did not affect the severity of acne in a majority
      of patients (64.20%). Significantly, a majority (80.62%) of patients noticed a
      summer aggravation due to sweating and increased humidity. Thus our study is at
      variance with the existing literature, with summer aggravation being the
      predominant complaint. We would like to propose that the increased temperature,
      marked humidity, and sweating might explain the results seen in our region.

PMID- 12227482
TI  - Comparative efficacy of various treatment regimens for androgenetic alopecia in
      men.
AB  - Our understanding of the aetiology of androgenetic alopecia (AGA) has
      substantially increased in recent years. As a result, several treatment
      modalities have been tried with promising results especially in early stages of
      AGA. However, as far as has been ascertained, there is no comprehensive study
      comparing the efficacy of these agents alone and in combination with each other.
      One hundered male patients with AGA of Hamilton grades II to IV were enrolled in
      an open, randomized, parallel-group study, designed to evaluate and compare the
      efficacy of oral finasteride (1 mg per day), topical 2% minoxidil solution and
      topical 2% ketoconazole shampoo alone and in combination. They were randomized
      into four groups. Group I (30 patients) was administered oral finasteride, Group
      II (36 patients) was given a combination of finasteride and topical minoxidil,
      Group III (24 patients) applied minoxidil alone and Group IV (10 patients) was
      administered finasteride with topical ketoconazole. Treatment efficacy was
      assessed on the basis of patient and physician assessment scores and global
      photographic review during the study period of one year. At the end of one year,
      hair growth was observed in all the groups with best results recorded with a
      combination of finasteride and minoxidil (Group II) followed by groups IV, I and
      III. Subjects receiving finasteride alone or in combination with minoxidil or
      ketoconazole showed statistically significant improvement (p<0.05) over minoxidil
      only recipients. No signifcant side-effects related to the drugs were observed.
      In conclusion, it is inferred that the therapeutic efficacy is enhanced by
      combining the two drugs acting on different aetiological aspects of AGA.

PMID- 12227483
TI  - KID syndrome: response to acitretin.
AB  - KID syndrome is rare. We report a 17-year-old girl who presented with universally
      ichthyotic red hue on the face, trunk, and extremities along with deafness and
      keratitis since childhood. She was diagnosed with KID syndrome. Treatment with
      acitretin cleared the hyperkeratotic ichthyotic lesions with little effect on the
      cornea or hearing. Acitretin seems to be a promising new treatment in KID
      syndrome.

PMID- 12227484
TI  - Lupus erythematosus associated with C1 inhibitor deficiency.
AB  - We report here a patient with skin lesions of lupus erythematosus (LE) associated
      with a type 1 hereditary C1 inhibitor deficiency. She had not experienced any
      episodes of angioedema. A histological examination of the affected skin lesions
      demonstrated liquefaction of the basal cell layer in the perifollicule. Direct
      immunofluorescence staining revealed the granular deposition of IgM along the
      dermo-epidermal junction. Blood laboratory examinations revealed low levels of
      CH50, C1q, C4, C2 and C1 inhibitor, but the C3 and C5 levels were within normal
      limits. Similar reductions in the C1 inhibitor levels were observed in 2 out of 3
      sisters. Although one sister has been asymptomatic until now, the other has
      suffered from SLE. The antinuclear antibody titer was negative initially, but has
      changed to positive. The skin lesions became pigmented following topical
      corticosteroid therapy, but the deficient complement component levels remained
      unchanged. We also reviewed 23 cases in the literature of hereditary C1 inhibitor
      deficiency associated with SLE, DLE, LE-like eruption, and SCLE and discussed
      several common characteristics such as a female predominance, a high incidence of
      antinuclear antibodies, cutaneous manifestations, and photosensitivity.

PMID- 12227485
TI  - Isolated plantar collagenoma: a case report.
AB  - Collagenoma is a hamartomatous lesion consisting of proliferation of normal
      collagen tissue. We describe a 19-year-old girl with a firm, elastic 3 x 2 cm
      nodule located on her right plantar fossa. Histopathologically, dense, coarse,
      thick collagen fibers were located in the dermis. In addition, the number of
      elastic fibers was slightly decreased. Based on these findings, the case was
      diagnosed as isolated plantar collagenoma.

PMID- 12227486
TI  - A case of hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber's disease)
      with dystrophic calcinosis cutis and retinal lesions.
AB  - A 65-year-old Japanese female developed a nodule on the distal
      interphalangealjoint of her right thumb. She also had multiple telangiectasias on
      her face, oral mucosa, tongue, nasal mucosa and upper extremities. A lip biopsy
      showed irregularly dilated capillaries and venules lined by flat endothelial
      cells. The nodule in the right thumb was resected. Histopathology revealed
      calcium deposits in the dermis. This case was diagnosed as dystrophic calcinosis
      cutis within hereditary hemorrhagic telangiectasia. Ophthalmologic examination
      showed bilateral retinal vascular lesions with dilated and tortuous retinal
      venules.

PMID- 12227487
TI  - A case of multiple Bowen's disease with squamous cell carcinoma of the larynx and
      adenocarcionoma of the prostate.
AB  - Bowen's disease, or cutaneous squamous cell carcinoma in situ, has been regarded
      as a cutaneous marker for internal malignancy. However, the relationship of
      Bowen's disease to visceral cancers remains controversial. We present a 76-year
      old male with multiple lesions of Bowen's disease, who later developed laryngeal
      cancer and subsequent prostate cancer with distant metastases. Efforts to detect
      possible common etiologic agents including human papillomavirus and chronic
      arsenicism revealed no association between Bowen's disease and the internal
      malignancies. Despite the controversy, we suggest that a conservative cancer
      workup is ethically indicated in patients with multiple Bowen's disease.

PMID- 12227488
TI  - Cutaneous hyalohyphomycosis and onychomycosis caused by Onychocola canadensis:
      report of the first case from Turkey.
AB  - We present the first Turkish case of skin and nail infection due to Onychocola
      canadensis in an otherwise healthy farmer who frequently worked barefoot on soil.
      Cutaneous involvement consisted of scaly and hyperkeratotic lesions resembling
      tinea pedis, erythematous plaques, and dermal papulonodules of various sizes
      simulating Majocchi's granuloma. Repeated cultures from nail plates, skin
      scrapings and needle aspiration materials from papules or nodules all yielded the
      same mold on Sabouroud dextrose media with and without cycloheximide,
      trichophyton agar, and potato dextrose agar at 26 degrees C. The causal isolate
      was identified as Onychocola canadensis Sigler gen. et sp. nov., a slow-growing
      arthroconidial hyphomycete, on the basis of its colonial and microscopic
      morphology. While skin lesions were responsive to daily itraconazole in a dose of
      200 mg for three months, the onychomycosis was resistant to therapy. To our
      knowledge, this is the first presentation of O. canadensis as the cause of
      cutaneous hyalohyphomycosis to date.

PMID- 12227490
TI  - Benign neonatal hemangiomatosis in a pre-term infant.
AB  - Benign neonatal hemangiomatosis (BNH) is a condition of multiple neonatal
      strawberry hemangiomas limited to the skin. Characteristically, a rapid
      proliferative growth phase is followed by a prolonged involutional phase.
      Regression of cutaneous lesions usually starts in the fourth month, but
      variations until complete involution are high for individial lesions.
      Disseminated neonatal hemangiomatosis (DNH) represents a serious multisystemic
      disorder with hemangiomas in different organs and the skin. Early evaluation of
      the patients and treatment of visceral hemangiomas is of crucial importance.
      While solitary hemangiomas have been reported to occur more commonly in pre-term
      infants, prematurity has rarely been described in the literature as being
      associated with BNH.

PMID- 12227489
TI  - A novelliposomal formulation of dithranol for psoriasis: preliminary results.
AB  - We have prepared a novel, aqueous gel-based, liposome-entrapped formulation of
      dithranol. Herein, we report preliminary observations on its efficacy,
      tolerability, and cosmetic acceptability in treating stable plaque psoriasis.
      Nineteen plaques of psoriasis in nine adult patients were treated for six weeks
      in a prospective, open-label trial. In five patients, there was total clearance
      of lesions, with more than 50% subsidence in a further two patients.
      Significantly, there were no reports of lesional or perilesional irritation, and
      only one patient showed faint brown staining of the skin, which was completely
      and rapidly reversible. These preliminary results indicate that our liposomal
      dithranol gel has potential advantages over presently available preparations of
      dithranol; these may translate into enhanced acceptance of this useful drug by
      patients and physicians.

PMID- 12227491
TI  - Solitary mastocytoma improved by intralesional injections of steroid.
AB  - Solitary mastocytoma is an uncommon disease characterized by monotonous
      infiltrations of mast cells that extend from papillary dermis to subcutaneous
      fat. They usually resolve by adulthood, and there is no satisfactory treatment
      other than waiting. A two-month-old Korean male infant with deep solitary
      mastocytoma was treated intralesionally with triamcinolone acetonide. His
      mastocytoma in medial malleolus was very distressing because it was very
      sensitive to friction, and he was just reaching the crawling stage. After three
      injections, his skin lesion flattened with marked decrease of erythema and
      subjective symptoms. His skin lesion has continued to have a good clinical
      response for 9 months after the last treatment.

PMID- 12227492
TI  - Adapalene in the treatment of melasma: a preliminary report.

PMID- 12227493
TI  - Response to article "Plantar verrucous carcinoma: report of a case treated with
      Boyd amputation followed by reconstruction with a free foream flap (J Dermatol,
      28,226-230,2001)".

PMID- 12227494
TI  - Behavior of HO-1-N-1, buccal mucosa carcinoma derived cells, on [Ca2+]i responses
      to stimulants.
AB  - Buccal mucosa carcinoma-derived cell line, HO-1-N-1, epithelial-like cells, was
      obtained in order to investigate the characteristics of oral cancer cells and
      examine the [Ca2+]i responses to stimulants, such as bradykinin (BK), histamine
      (HIST), thapsigargin (TG), epidermal growth factor (EGF) and transforming growth
      factor alpha (TGF alpha ). Intracellular Ca2+ influx was observed by all
      stimulants that enhanced the [Ca2+]i response. However, intracellular Ca2+
      release was not observed in response to growth factors. The [Ca2+]i response of
      BK (100 nM) was inhibited by 10 micro M of the BKB2 antagonist, D-Arg-[Hyp3,
      Thi5,8, D-Phe7]-BK, and HIST (1 mM) was completely inhibited by 100 nM of the H1
      antagonist, (+)-chlorpheniramine, in the presence and absence of extracellular
      Ca2+ (1.5 mM).

PMID- 12227495
TI  - Malignant potential of the reticular form of oral lichen planus over a 25-year
      observation period in 55 patients from Slovenia.
AB  - A retrospective evaluation of the reticular form of oral lichen planus was made
      on the basis of clinical and histopathological observations in 55 patients.
      Patients were re-examined once every six months over a 25-year period. Biopsies
      were taken from all lesions. No cases of complete remission and no cases of
      malignant transformation were recorded. Our findings suggest that the reticular
      form of oral lichen planus is not a precancerous lesion.

PMID- 12227496
TI  - Compound odontoma with granular cells.
AB  - The authors present an interesting and unusual histology of compound odontoma
      from an 18-year-old female. Part of the subepithelial connective tissue beneath
      the enamel organ epithelium was replaced by a granular cell nodule, of a probable
      histiocytic nature. This case represents the first published report of odontoma
      accompanied by granular cells.

PMID- 12227497
TI  - Malignancy in oral lichen planus: a review of a group from the Malaysian
      population.
AB  - The objective of this study was to determine the socio-demography (age, race and
      gender) of a group of Malaysian patients who were diagnosed as suffering from
      oral lichen planus (OLP). The occurrence of malignancy was also investigated. A
      total of 77 clinical and biopsy records of patients with OLP were studied.
      Females were affected more than males, with the female to male ratio being 2:1.
      Middle-aged Indian and Chinese females tend to be affected by OLP when compared
      with the rest of the population. Only 19 patients returned for further follow-up.
      One adult Indian female with a six-year history of lichenoid reaction showed the
      presence of malignancy.

PMID- 12227498
TI  - Oral self-care behavior among dental school students in Greece.
AB  - The purpose of this study was to determine the oral health attitudes/behavior of
      Greek dental students. The subjects (n = 539) were officially registered students
      at the University of Athens Dental School. Their oral health behavior was
      assessed with the use of a 12-graded-item questionnaire. A significant increase
      per year of study was observed in the number of students reporting careful
      brushing of the teeth [OR: 1.1 (1.0-1.3)] and being able to clean their teeth
      well without the use of toothpaste [OR: 2.5 (2.0-3.1)]. Each year of education
      significantly increased the probability of disagreement with statements such as:
      "I think my teeth are getting worse despite my daily brushing" [OR: 1.5 (1.2
      1.9)], "It is impossible to prevent gum disease with tooth-brushing alone" [OR:
      1.3 (1.1-1.5)], and "I put off going to the dentist until I have a toothache"
      [OR: 1.3 (1.2-1.6)]. Examination of the summary questionnaire score revealed that
      females presented significantly higher total scores. All scores increased
      significantly in the fourth and fifth years of dental studies. During the years
      of university study, the score variation and favorable attitudes/ behavior toward
      oral health appear to reflect the variation in the students' educational training
      experience.

PMID- 12227499
TI  - Finite element analysis of forces created by root separation and resection
      modelling.
AB  - Natural teeth with a healthy periodontal support exhibit stress transfer when
      functional forces are applied to them. These stress patterns show considerable
      variations during differing treatment modalities, which may influence both the
      tooth and supporting alveolar bone. The purpose of this study was to evaluate
      variations in the stress transfer under functional loads on first molars with
      periodontal furcation involvement, which were treated either with by root
      resection or root separation. This study used a two dimensional mathematical
      model of a mandibular first molar that was subjected to either a root separation
      or a root resection procedure. An evenly distributed dynamic load (600 N) was
      applied on two buccal cusps and distal fossae of the molar in centric occlusion.
      The analysis was performed using an IBM-compatible computer running standard
      analysis software. It was found that in the root resection model the stress
      values were maximum on the centre of rotation, and compressive stresses increased
      towards the middle of the cervical line. For the root separation model, the
      maximum shear stress values were observed in the distal portion, and a uniform
      stress distribution was observed in the mesial portion. Shear stress values for
      bone increased towards the centre in the bifurcation area. The outcomes of this
      study may be useful as a guide in clinical restorative procedures.

PMID- 12227500
TI  - Effects of selenium on the structure of the mandible in experimental diabetics.
AB  - In the treatment of diabetes-induced pathologies, beneficial results have been
      obtained with administration of antioxidants. Selenium is an antioxidant and
      essential trace element in living organisms. The aim of this study was to
      investigate the possible effects of selenium on the structural alterations of the
      mandible due to diabetes. In this study thirty-nine Wistar rats were used and a
      control, a selenium given control, a diabetic and a selenium given diabetes
      groups were formed. Experimental diabetes was induced by a single i.p. injection
      (50 mg/kg) of streptozotocin (STZ). The diabetic + selenium and the control +
      selenium groups were injected with a daily dose of 5 micro mol/kg/day sodium
      selenite (i.p.) for 4 weeks while the diabetic and the control groups were
      injected with distilled water. Mandibles of all the animals were excised and
      examined at the 5th week. High blood glucose level and low body weight in the
      diabetic group were not significantly affected by selenium administration.
      Furthermore, a negligible increase in blood glucose level was observed in the
      selenium given control group. Densitometric analysis revealed a significant
      reduction in bone density and presence of resorption in the diabetic and the
      selenium given control groups as compared to the selenium given diabetes and the
      control groups. In X-ray diffraction analysis, the reduction in peak intensity of
      the reflected light in both the diabetic and the selenium given control groups
      indicated a possible alteration in the crystallinity or a poor crystalline
      substance. Histological investigation showed that there was progressive
      resorption, trabecular and cortical irregularity and vascular proliferation in
      the diabetic and the selenium given control groups, whereas a more healthy
      appearance was detected in the selenium given diabetes group. The results of this
      study suggest the positive effects of selenium on diabetes-induced structural
      alterations in the mandible. However, the unexpected results in the selenium
      given control group necessitate further studies on the mechanism of selenium
      effects in organisms.

PMID- 12227501
TI  - The accuracy of three different electronic root canal measuring devices: an in
      vitro evaluation.
AB  - The main objective of this in vitro study was to evaluate the effects of the
      operator's experience level and pre-flaring on the accuracy of the results of
      three different brands of a new generation of root canal measuring devices, as
      well as the comparison among them. Extracted human teeth were prepared and then
      actual length and electronic length measurements were made by three different
      operators according to a double-blind technique. Three different operators
      performed electronic measurements on each specimen separately with three
      different electronic root canal measuring devices using in vitro models.
      Measurements were repeated by all operators after the pre-flaring. Taking the
      clinical tolerance of +/- 0.5 mm into account, there was no statistically
      significant difference between the accuracy of the instruments (P > 0.01).
      However, the results obtained from the Bingo electronic apex locator in pre
      flared canals by the beginner operator were statistically significant (P < 0.01).
      All of the instruments had a clinically acceptable result at the tolerance of +/-
      0.5 mm. If the instruments are used in accordance with the manufacturer's
      instructions, experience with electronic root canal measurement is not essential.
      However, the operator has to be more careful when working on pre-flared canals.

PMID- 12227502
TI  - Imprint cytology of ameloblastoma.
AB  - To reveal the characteristic features of the imprint cytology of ameloblastomas,
      we compared these features with the histopathological features of the same
      specimens. Twenty-five cases, histopathologically diagnosed as ameloblastoma,
      were used. Three cell types were recognized: small squamous epithelial cells
      which were polyhedral or spindle-shaped with some projections; naked cells with
      poorly defined cytoplasm showing tubular and palisade patterns in some areas; and
      large squamous epithelial cells with extensive wrinkled cytoplasm. Naked cells
      and small squamous epithelial cells were thought to correspond to the
      histopathological classifications of cuboidal to columnar cells, and polyhedral
      or spindle cells respectively. Large squamous epithelial cells were thought to be
      acanthomatous cells showing squamous metaplasia. Imprint cytology had
      characteristic advantages compared to fine needle aspiration cytology, and
      clearly reflected the histopathology of the lesions. Knowledge of the
      characteristic features of the cells observed in imprint cytology is important
      when undertaking cytodiagnosis using fine needle aspiration.

PMID- 12227504
TI  - Establishment and characterization of a lymphoepithelial-like carcinoma cell line
      (HUUCLEC) derived from the human uterine cervix.
AB  - A cell line designated HUUCLEC was established from a human uterine cervical
      lymphoepithelial carcinoma obtained from a 61-year-old Japanese woman. The cell
      line has grown slowly without interruption and serial passages were successively
      carried out 60 times within 3 years. The cultured cells were spindle or round in
      shape, showing anaplastic and pleomorphic features, a pavement cell arrangement
      and multilayering without contact inhibition. The population doubling time of the
      HUUCLEC line was 72 hours while the chromosomal number varied widely and showed
      aneuploidy. The modal chromosomal number was stable at the triploid range and
      marker chromosomes were present; the Ebstein-Barr virus was absent in the
      cultured cells.

PMID- 12227505
TI  - Retention of arsenic on hydrous ferric oxides generated by electrochemical
      peroxidation.
AB  - Electrochemical peroxidation (ECP), an emerging remediation technology, with
      direct electric current applied to steel electrode and small addition of H2O2,
      was used to remove As(III) from contaminated aqueous solutions. Bench scale
      experiments were conducted to evaluate the sorption and distribution of arsenic
      between the soluble and solid state hydrous ferric oxides (HFO) formed as part of
      the ECP process. ECP was effective in removing arsenic from the aqueous solution,
      with >98% of the applied As(III) adsorbed on HFO. Removal was complete within 3
      min of ECP treatment and apparently independent of the initial pH of the water
      (3.5-9.5). In the absence of H2O2 more As(III) was adsorbed by solid state iron
      at pH 9.5 than at 3.5 (2600 vs. 1750 microg l(-1)). Thus H2O2 was crucial to
      oxidize As(III) to As(V) which is more strongly retained by HFO. Removal of As
      was not significantly affected by the concentration of H2O2 or by current
      processing time. The optimal operating conditions were pH < 6.5, H2O2
      concentration of 10 mg l(-1) and current process time not exceeding 3 min. X-ray
      diffraction (XRD), diffuse-reflectance infrared Fourier transform (DRIFT)
      spectroscopy and transmission electron microscopy (TEM) were applied to study the
      HFO deposits. The XRD data indicated the prevalence of poorly ordered Fe minerals
      in the suspended ECP solids with a dominance of 5 line ferrihydrite in the
      absence of H2O2. At pH 3.5 and with 100 mg H2O2 l(-1), akaganeite was formed,
      whereas an incipient hematitic phase, reflection at 0.39 nm, occurred at pH 6.5.
      DRIFT data indicate that both As(III) and As(V) were specifically adsorbed onto
      HFO at acid and neutral pH. TEM observations indicated the presence of spherical
      shape ferrihydrite and provided evidence for possible formation of subrounded
      hematite and acicular shape goethite.

PMID- 12227503
TI  - HEC-1 cells.
AB  - HEC-1 cell line was the first in vitro cell line of a human endometrial
      adenocarcinoma which enabled us to perform research work on the endometrium and
      endometrial carcinoma at a simplified cellular system, contributing cell and
      molecular biological studies on endometrial carcinoma. Once a cell line is
      established, it provides a stable experimental system that facilitates and
      progresses in the study of the tissues and/or neoplasias from which they are
      derived. In this article we report how HEC-1 cells have been established and
      cleared the proposed requirements to characterize the established cell line. Also
      to show the usefulness of the cell line for research work, once it was
      established, we illustrate these concepts by recalling results obtained with HEC
      1 cells and reviewing the literature on what has been achieved by using these
      cells.

PMID- 12227506
TI  - Reductive dechlorination of chlorinated methanes in cement slurries containing
      Fe(II).
AB  - Degradative solidification/stabilization (DS/S) is a novel remediation technology
      that combines chemical degradation with conventional
      solidification/stabilization. The applicability of the Fe(II)-based DS/S to
      treating chlorinated alkanes was tested by characterizing degradation reactions
      of carbon tetrachloride (CT) and its daughter products in cement slurries
      containing Fe(II). Degradation kinetics of CT and chloroform (CF) were generally
      very rapid with reaction rates comparable to rates that can be obtained with zero
      valent iron. Dechlorination reactions of CT proceeded primarily via a
      hydrogenolysis pathway, which yielded CF and methylene chloride (MC) as major
      products and chloromethane and methane as minor products. However, reaction
      pathways other than hydrogenolysis also appeared to be important at very high pH
      conditions. MC apparently was resistant to dechlorination reactions over a period
      of about two months. Kinetics of CT and CF transformation were strongly dependent
      on pH with an optimal value around 13, which was higher than found previously for
      PCE. When the initial CF concentration varied between 0.01 and 1 mM, and the
      Fe(II) dose was 104 mM, pseudo-first-order kinetics generally described the
      degradation reactions of CF. However, there was also some indication of substrate
      saturation kinetics in these experiments. This suggests that a saturation model
      would better describe the kinetics in systems with higher concentration of
      substrates or lower concentration of the reactive surfaces.

PMID- 12227507
TI  - Effects of solution conditions on the precipitation of phosphate for recovery. A
      thermodynamic evaluation.
AB  - To understand the effects of solution conditions on the precipitation of calcium
      phosphates from wastewater for recovery, a computer programme PHREEQC was
      employed to calculate the speciation and saturation-index (SI) with respect to
      hydroxyapatite of a chemically defined precipitation system, which contains
      phosphate of 1-200 mg P/l, with Ca/P molar ratios of one to 10 times of the
      stoichiometric calcium to phosphorus molar ratio of hydroxyapatite, at a pH range
      of 7.0-11.0. The results show that the SI is respectively the logarithmic
      function of the phosphate concentration and the calcium concentration, increasing
      with the increase of either of them; the SI is a polynomial function of the
      solution pH value and increases with its increase, and the effect of solution pH
      value is due to its influence on base uptake of the precipitation reaction and
      the speciation of phosphate and calcium ions; the SI is also a logarithmic
      function of the solution ionic strength but decreases with its increase; at the
      temperature range of 5-30 degrees C the SI increases linearly with solution
      temperature and the effect of temperature is also due to its influence on the
      speciation of phosphate and calcium ions.

PMID- 12227508
TI  - Using stochastic risk assessment in setting information priorities for managing
      dioxin impact from a municipal waste incinerator.
AB  - The objectives of this study were to assess site-specific carcinogenic risk of
      incinerator-emitted dioxins in a manner reflecting pollutant transfer across
      multimedia and multi-pathways. The study used site-specific environmental and
      exposure information and combined the Monte Carlo method with multimedia modeling
      to produce probability distributions of risk estimates. The risk estimates were
      further categorized by contaminated environmental media and exposure pathways
      that are experienced by human receptors in order to pinpoint significant sources
      of risk. Rank correlation coefficients were also calculated along with the Monte
      Carlo sampling to identify key factors that influenced estimation of risk. The
      results showed that ingestion accounted for more than 90% of the total risk and
      that risk control on ingestion of eggs, aboveground vegetables, and poultry
      should receive priority. It was also found that variation of parameters with
      variability accounted for around 35% of the total risk variance, while
      uncertainty contributed to the remaining 65%. Intake rates of aboveground
      vegetables, eggs, and poultry were the key parameters with the largest
      contribution to variance. In addition, sufficient sampling and analysis of dioxin
      contents in eggs, aboveground vegetables, poultry, soil, and fruit should be
      performed to improve risk estimation because the variation in concentrations in
      these media accounted for the largest overall risk variance. Finally, focus
      should be placed on reduction of uncertainty associated with the risk estimation
      through ingestion of aboveground vegetables, eggs, poultry, fruit, and soil
      because the risk estimates associated with these exposure pathways had the
      largest variance.

PMID- 12227509
TI  - Preparation of agricultural residue anion exchangers and its nitrate maximum
      adsorption capacity.
AB  - Anion exchangers were prepared from different agricultural residues (AR) after
      reaction with epichlorohydrin and dimethylamine in the presence of pyridine and
      N,N-dimethylformamide (EDM method). Agricultural residues anion exchangers (AR
      AE) produced by the EDM method were inexpensive and showed almost the same NO3-
      removal capacities as Amberlite IRA-900. AR-AE produced from AR with higher
      hemicelluloses, lignin, ash and extractive contents resulted in the lower yields.
      Sugarcane bagasse with the highest alpha-cellulose contents of 51.2% had the
      highest yield (225%) and lowest preparation cost. The highest maximum adsorption
      capacity (Qmax) for nitrate was obtained from rice hull (1.21 mmol g(-1)) and
      pine bark natural exchangers (1.06 mmol g(-1)). No correlation was found between
      Qmax and alpha-cellulose content in the original AR. AR-AE produced from
      different AR demonstrated comparable Qmax due to the removal of non-active
      compounds such as extractives, lignin and hemicelluloses from AR during the
      preparation process. Similar preparation from pure cellulose and pure alkaline
      lignin demonstrated that the EDM method could not produce anion exchangers from
      pure lignin due to its solubilization after the reaction with epichlorohydrin.

PMID- 12227510
TI  - Heterogeneous water phase catalysis as an environmental application: a review.
AB  - Catalytic water phase processes as an environmental application is a relatively
      novel subject with tremendous potential in the near future. This review of 120
      references presents the wide scale of heterogeneous water phase applications
      studied mainly within past five years. Both oxidation and hydrogenation processes
      are included as well as TiO2 assisted photocatalysis. According to the
      references, heterogeneous catalysis is developing rapidly. New bimetallic
      catalysts and supports with higher surface area have improved catalytic
      efficiency in both oxidation and hydrogenation processes. It also seems that
      study on use of some waste materials such as red mud as catalyst is a very
      progressive field. On the whole, the chemical aspects are pretty well known, but
      the catalyst durability, and in many cases activity as well, has to be improved.

PMID- 12227511
TI  - Profiles of PAH emission from steel and iron industries.
AB  - In order to characterize the polycyclic aromatic hydrocarbons (PAHs) emission
      from steel and iron industries, this study measured the stack emission of twelve
      steel and iron plants in southern Taiwan to construct a set of source
      fingerprints. The study sampled the emissions by the USEPA's sampling method 5
      with the modification of Graseby for the gas and particulate phase PAH and, then,
      used Hewlett-Packard 5890 gas chromatograph equipped with mass spectrometer
      detector to analyze the samples. The steel and iron industries are classified
      into three categories on the basis of auxiliary energy source: Category I uses
      coal as fuel, Category II uses heavy oil as fuel and Category III uses electric
      arc furnace. The pollution source profiles are obtained by averaging the ratios
      of individual PAH concentrations to the total concentration of 21 PAHs and total
      particulate matter measured in this study. Results of the study show that low
      molecular weight PAHs are predominant in gas plus particulate phase for all three
      categories. For particulate phase PAHs, however, the contribution of large
      molecular weight compounds increases. Two-ring PAHs account for the majority of
      the mass, varying from 84% to 92% with an average of 89%. The mass fractions of 3
      , 4-, 5-, 6-ring PAHs in Category I are found to be more than those of the other
      two categories. The mass of Category III is dominated by 7-ring PAHs. Large (or
      heavy) molecular weight PAHs (HMW PAHs) are carcinogenic. Over all categories,
      these compounds are less than 1% of the total-PAH mass on the average. The
      indicatory PAHs are benz[a]anthracene, benzo[k]fluoranthene, benzo[ghi]perylene
      for Category I, benzo[a]pyrene, acenaphthene, acenaphthylene for Category II and
      coronene, pyrene, benzo[b]chrycene for Category III. The indicatory PAHs among
      categories are very different. Thus, dividing steel and iron industry into
      categories by auxiliary fuel is to increase the precision of estimation by a
      receptor model. Average total-PAH emission factors for coal, heavy oil and
      electric arc furnace were 4050 microg/kg-coal, 5750 microg/l-oil, 2620 microg/kW
      h, respectively. Carcinogenic benzo[a]pyrene for gas plus particulate phase was
      2.0 g/kg-coal, 2.4 microg/l-oil and 1.4 microg/kW h for Category I, II and III,
      respectively.

PMID- 12227512
TI  - Estimation of surface area of montmorillonite by ethylene oxide chain adsorption.
AB  - This study investigates the feasibility of using ethylene oxide chain adsorption
      to determine the surface area of an expandable clay, montmorillonite.
      Experimental results indicate that high molecular weight poly(ethylene oxide) or
      nonionic surfactant with long ethylene oxide chain should be used to provide
      reasonable estimations for monolayer capacity. The method has advantages over
      Brunauer, Emmett, and Teller method in that it is readily applicable to a wide
      range of areas, particularly to 2:1 layer silicates under aqueous conditions.

PMID- 12227513
TI  - Enhancement of copper and cadmium adsorption on kaolin by the presence of humic
      acids.
AB  - The competitive adsorption equilibrium isotherms of Cu2+ and Cd2+ on kaolin have
      been measured at 298 K, in the presence and the absence of humic acids (HAs). HAs
      were found to enhance the metal adsorption capacity of mineral surfaces, in
      particular kaolin. This enhancement was also observed in the competitive
      adsorption of copper and cadmium on kaolin and kaolin-HA complex. This
      competitive adsorption shows that the presence of Cd2+ has not an important
      effect on Cu2+ adsorption, whereas a dramatic decrease is observed on the
      adsorption of Cd2+ in the presence of Cu2+. The Freundlich isotherm equation was
      found to provide an excellent fit to the experimental data. These results were
      compared with the independent adsorption of both heavy metals.

PMID- 12227514
TI  - Synergetic effects of anodic-cathodic electrocatalysis for phenol degradation in
      the presence of iron(II).
AB  - A novel electrocatalysis method for phenol degradation was described using a beta
      PbO2 anode modified with fluorine resin and a Ni-Cr-Ti alloy cathode. In case of
      air sparging at the cathodic zone, the techniques of anodic-cathodic
      electrocatalysis (ACEC) and ferrous ion catalyzed anodic-cathodic
      electrocatalysis (FACEC) in the presence of iron(II) were developed. Both of ACEC
      and FACEC were more effective than anodic electrocatalysis (AEC). The percentage
      of phenol eliminated by FACEC could increase by nearly 30% compared with that of
      AEC, and the current efficiency could reach to 70%. Important operating factors
      such as ferrous ion concentration, air-sparging rate and applied current were
      investigated and it was found that such beneficial effects could be achieved at a
      suitable current and ratio of the concentration of ferrous ion to the air
      sparged. The mechanism of phenol degradation is proposed to be the generation of
      hydroxyl radicals concerned with the two electrodes. Results also indicated that
      the process provided an efficient way to regenerate ferrous ion compared with the
      conventional Fenton's system.

PMID- 12227515
TI  - Hydrogenolysis of chlorobenzene, dichlorobenzenes and chlorotoluenes by in situ
      generated and gaseous hydrogen in alkaline media and the presence of Pd/C
      catalyst.
AB  - A method for dechlorination of chloroaromatic compounds at room temperature and
      atmospheric pressure by an in situ generated--in reaction of Al particles with
      water--or gaseous hydrogen in alkaline media and the presence of Pd/C catalyst
      was thoroughly investigated, having in mind its possible application in
      utilization of organochlorine waste. Conversion degree to dechlorinated compounds
      depended on the constitution of substrates and ranged between 88% and 96% when in
      situ hydrogen was used (at substrate (chlorine) to catalyst molar ratio 550:1 and
      over twofold stoichiometric excess of Al relative to substrate (chlorine); the
      process lasted ca. 26 h until all Al was consumed), or 90-97% if gaseous hydrogen
      was purged. Effectiveness of dechlorination was markedly affected by stirring,
      i.e. size of the stirrer and speed of revolution. Prospects for application of
      the method described were briefly outlined.

PMID- 12227516
TI  - The enhancement of photodegradation efficiency using Pt-TiO2 catalyst.
AB  - This study investigates the mechanism of photosensitization and the recombination
      of excited electron-hole pairs affected by depositing platinum (Pt) on the
      surface of titanium dioxide (TiO2). A new catalyst of Pt-TiO2 was prepared by a
      photoreduction process. Being model reactions, the photocatalytic oxidation of
      methylene blue (MB) and methyl orange (MO) in aqueous solutions using the Pt-TiO2
      catalyst was carried out under either UV or visible light irradiation. The
      experimental results indicate that an optimal content of 0.75%Pt-TiO2 achieves
      the best photocatalytic performance of MB and MO degradation and that the Pt-TiO2
      catalyst can be sensitized by visible light. The interaction of Pt and TiO2 was
      investigated by means of UV-Vis absorption spectra, photoluminescence emission
      spectra, and X-ray photoelectron emission spectroscopy. The Pt0, Pt2+ and Pt4+
      species existing on the surface of Pt-TiO2, and the Ti3+ species existing in its
      lattice may form a defect energy level. The Pt impurities, including Pt, Pt(OH)2,
      and PtO2, and the defect energy level absorb visible light more efficiently in
      comparison with the pure TiO2 and hinder the recombination rate of excited
      electron-hole pairs.

PMID- 12227517
TI  - Polychlorinated biphenyls in different trophic levels from a shallow lake in
      Argentina.
AB  - Polychlorinated biphenyls (PCBs) were determined in a aquatic community from Los
      Padres Lake, Argentina. Twenty four PCB congeners from tri- to octa-chlorinated
      isomers were detected and quantified using conventional gas chromatography with
      electron capture detector (GC-ECD). The aim of this study was to investigate the
      concentrations of PCBs in freshwater organisms from a shallow lake of Argentina.
      Stems of bulrush (Schoenoplectus californicus), whole tissues of false
      loosestrife (Ludwigia sp.) and grass shrimp (Palaemonetes argentinus), and liver,
      gonads, muscle and mesenteric fat (if present) of fish species (Rhamdia sapo) and
      (Oligosarcus jenynsi) were analyzed. Two areas were selected to macrophytes
      sampling: the input area, main PCB source of the lake (Station 1), and the output
      area, a potential anoxic zone (Station 2). Macrophytes from Station I
      bioconcentrated higher total PCB levels than Station 2, showing that the former
      have received PCBs washed down from upstream areas. Penta- and hexa-congeners
      were enriched relative to other congeners in animal biota and macrophytes from
      Station 1, consistent with commercial mixture of Aroclor 1254 used in this
      region. In bulrush from Station 2 a predominance of tri- and tetra-chlorinated
      congeners was observed. Grass shrimp showed the lowest PCB values among animal
      biota. PCB concentrations in fish tissues varied with the species and the gonadal
      development. Mesenteric fat, only present in post-spawning organisms of R. sapo,
      had the highest values of PCBs relative to other tissues. A clearance of total
      PCBs in ovaries of post-spawning females of R. sapo was observed, but not in
      testes. O. jenynsil P. argentinus biomagnification factor (BMF) had a mean value
      of 18.7. Congeners 44, 52 and 151, showed the highest BMF values, being 64, 66
      and 62, respectively. These values would be a consequence of the low depuration
      rate of 44 and 52 congeners with orthochlorine substitution conducted by O.
      jenynsi and the high depuration rate of congener 151, which lacks 4 4'- chlorine
      substitution, carried out by grass shrimp. Although the most of congeners have
      been biomagnified, they did not clearly displayed a concomitantly increasing with
      log K(ow).

PMID- 12227518
TI  - The biology of impact craters--a review.
AB  - Impact craters contain ecosystems that are often very different from the
      ecosystems that surround them. On Earth over 150 impact craters have been
      identified in a wide diversity of biomes. All natural events that can cause
      localized disruption of ecosystems have quite distinct patterns of rccovery.
      Impact events are unique in that they are the only extraterrestrial mechanism
      capable of disrupting an ecosystem locally in space and time. Thus, elucidating
      the chronological sequence of change at the sites of impacts is of ecological
      interest. In this synthetic review we use the existing literature, coupled with
      our own observations at the Haughton impact structure, Devon Island, Nunavut,
      Canada to consider the patterns of biological recovery at the site of impact
      craters and the ecological characteristics of impact craters. Three phases of
      recovery are suggested. The Phase of Thermal Biology, a phase associated with the
      localized, ephemeral thermal anomaly generated by an impact event. The Phase of
      Impact Succession and Climax, a phase marked by multiple primary and secondary
      succession events both in the aquatic realm (impact crater-lakes) and terrestrial
      realm (colonization of paleolacustrine deposits and impact-generated substrata)
      that are followed by periods of climax ecology. In the case of large-scale impact
      events (> 10(4) Mt), this latter phase may also be influenced by successional
      changes in the global environment. Finally, during the Phase of Ecological
      Assimilation, the disappearance of the surface geological expression of an impact
      structure results in a concomitant loss of ecological distinctiveness. In extreme
      cases, the impact structure is buried. Impact succession displays similarities
      and differences to succession following other agents of ecological disturbance,
      particularly volcanism.

PMID- 12227519
TI  - Occupancy frequency distributions: patterns, artefacts and mechanisms.
AB  - Numerous hypotheses have been proposed to explain the shape of occupancy
      frequency distributions (distributions of the numbers of species occupying
      different numbers of areas). Artefactual effects include sampling
      characteristics, whereas biological mechanisms include organismal, niche-based
      and meta-population models. To date, there has been little testing of these
      models. In addition, although empirically derived occupancy distributions
      encompass an array of taxa and spatial scales, comparisons between them are often
      not possible because of differences in sampling protocol and method of
      construction. In this paper, the effects of sampling protocol (grain, sample
      number, extent, sampling coverage and intensity) on the shape of occupancy
      distributions are examined, and approaches for minimising artefactual effects
      recommended. Evidence for proposed biological determinants of the shape of
      occupancy distributions is then examined. Good support exists for some mechanisms
      (habitat and environmental heterogeneity), little for others (dispersal ability),
      while some hypotheses remain untested (landscape productivity, position in
      geographic range, range size frequency distributions), or are unlikely to be
      useful explanations for the shape of occupancy distributions 'species specificity
      and adaptation to habitat, extinction-colonization dynamics). The presence of a
      core (class containing species with the highest occupancy) mode in occupancy
      distributions is most likely to be associated with larger sample units, and small
      homogenous sampling areas positioned well within and towards the range centers of
      a sufficient proportion of the species in the assemblage. Satellite (class with
      species with the lowest occupancy) modes are associated with sampling large,
      heterogeneous areas that incorporate a large proportion of the assemblage range.
      However, satellite modes commonly also occur in the presence of a core mode, and
      rare species effects are likely to contribute to the presence of a satellite mode
      at most sampling scales. In most proposed hypotheses, spatial scale is an
      important determinant of the shape of the observed occupancy distribution.
      Because the attributes of the mechanisms associated with these hypotheses change
      with spatial scale, their predictions for the shape of occupancy distributions
      also change. To understand occupancy distributions and the mechanisms underlying
      them, a synthesis of pattern documentation and model testing across scales is
      thus needed. The development of null models, comparisons of occupancy
      distributions across spatial scales and taxa, documentation of the movement of
      individual species between occupancy classes with changes in spatial scale, as
      well as further testing of biological mechanisms are all necessary for an
      improved understanding of the distribution of species and assemblages within
      their geographic ranges.

PMID- 12227520
TI  - Snake phylogeny based on osteology, soft anatomy and ecology.
AB  - Relationships between the major lineages of snakes are assessed based on a
      phylogenetic analysis of the most extensive phenotypic data set to date (212
      osteological, 48 soft anatomical, and three ecological characters). The marine,
      limbed Cretaceous snakes Pachyrhachis and Haasiophis emerge as the most primitive
      snakes: characters proposed to unite them with advanced snakes (macrostomatans)
      are based on unlikely interpretations of contentious elements or are highly
      variable within snakes. Other basal snakes include madtsoiids and Dinilysia--both
      large, presumably non-burrowing forms. The inferred relationships within extant
      snakes are broadly similar to currently accepted views, with scolecophidians
      (blindsnakes) being the most basal living forms, followed by anilioids
      (pipesnakes), booids and booid-like groups, acrochordids (filesnakes), and
      finally colubroids. Important new conclusions include strong support for the
      monophyly of large constricting snakes (erycines, boines. pythonines), and
      moderate support for the non-monophyly of the trophidophiids' (dwarf boas). These
      phylogenetic results are obtained whether varanoid lizards, or amphisbaenians and
      dibamids, are assumed to be the nearest relatives (outgroups) of snakes, and
      whether multistate characters are treated as ordered or unordered. Identification
      of large marine forms, and large surface-active terrestrial forms, as the most
      primitive snakes contradicts with the widespread view that snakes arose via
      minute, burrowing ancestors. Furthermore, these basal fossil snakes all have long
      flexible jaw elements adapted for ingesting large prey ('macrostomy'), suggesting
      that large gape was primitive for snakes and secondarily reduced in the most
      basal living foms (scolecophidians and anilioids) in connection with burrowing.
      This challenges the widespread view that snake evolution has involved
      progressive, directional elaboration of the jaw apparatus to feed on larger prey.

PMID- 12227521
TI  - Roles of synorganisation, zygomorphy and heterotopy in floral evolution: the
      gynostemium and labellum of orchids and other lilioid monocots.
AB  - A gynostemium, comprising stamen filaments adnate to a syncarpous style, occurs
      in only threc groups of monocots: the large family Orchidaceae (Asparagales) and
      two small genera Pauridia (Hypoxidaceae: Asparagales) and Corsia (Corsiaceae,
      probably in Liliales), all epigynous taxa. Pauridia has actinomorphic
      (polysymmetric) flowers, whereas those of Corsia and most orchids are strongly
      zygomorphic (monosymmetric) with a well-differentiated labellum. In Corsia the
      labellum is formed from the outer median tepal (sepal), whereas in orchids it is
      formed from the inner median tepal (petal) and is developmentally adaxial (but
      positionally abaxial in orchids with resupinate flowers). Furthermore, in orchids
      zygomorphy is also expressed in the stamen whorls, in contrast to Corsia. In
      Pauridia a complete stamen whorl is suppressed, but the 'lost' outer whorl is
      fused to the style. The evolution of adnation and zygomorphy are discussed in the
      context of the existing phylogenetic framework in monocotyledons. An arguably
      typological classification of floral terata is presented, focusing on three
      contrasting modes each of peloria and pseudopeloria. Dynamic evolutionary
      transitions in floral morphology are assigned to recently revised concepts of
      heterotopy (including homeosis) and heterochrony, seeking patterns that delimit
      developmental constraints and allow inferences regarding underlying genetic
      controls. Current evidence suggests that lateral heterotopy is more frequent than
      acropetal heterotopy, and that full basipetal heterotopy does not occur.
      Pseudopeloria is more likely to generate a radically altered yet functional
      perianth, but is also more likely to cause acropetal modification of the
      gynostemium. These comparisons indicate that there are at least two key genes or
      sets of genes controlling adnation, adaxial stamen suppression and labellum
      development in lilioid monocots; at least one is responsible for stamen adnation
      to the style (i.e. gynostemium formation), and another controls adaxial stamen
      suppression and adaxial labellum formation in orchids. Stamen adnation to the
      style may be a product of over-expression of the genes related to epigyny (i.e. a
      form of hyper-epigyny). If, as seems likely, stamen-style adnation preceded
      zygomorphy in orchid evolution, then the flowers of Pauridia may closely resemble
      those of the immediate ancestors of Orchidaceae, although existing molecular
      phylogenetic data indicate that a sister-group relationship is unlikely. The
      initial radiation in Orchidaceae can be attributed to the combination of hyper
      epigyny, zygomorphy and resupination, but later radiations at lower taxonomic
      levels that generated the remarkable species richness of subfamilies Orchidoideae
      and Epidendroideae are more likely to reflect more subtle innovations that
      directly influence pollinator specificity, such as the development of stalked
      pollinaria and heavily marked and/or spur-bearing labella.

PMID- 12227522
TI  - Carbohydrates: a limit on bacterial diversity within the colon.
AB  - The human large intestine is recognised as a physiologically important organ
      responsible for the conservation of water and salts. Through its resident
      bacteria, it is also capable of complex, enzyme catalysed, hydrolytic-digestive
      functions that have a high biological impact on the host. These microorganisms
      metabolise dietary components, principally complex carbohydrates that are not
      hydrolysed or absorbed in the upper gastrointestinal tract, and in this way,
      sequester energy for the host, through fermentation. This process involves a
      series of anaerobic, energy-yielding, catabolic reactions which complete
      digestive processes in the gut, resulting in end products that in turn influence
      the distribution of microbial species present as well as having some systemic
      effects. Some of the bacteria are thought to possess important health-promoting
      activities, especially with respect to their influence on mucosal and systemic
      immune responses to disease. These bioactivities can be modulated by substrates
      that support and influence microbial development, growth and survival. For these
      reasons, it is necessary to review dietary factors that may delimit bacterial
      diversity, to be able to predict responses and sensitivities to various
      environmental pressures and manipulations that occur in this area of human
      microbiology.

PMID- 12227523
TI  - Sirolimus-eluting stents: the novel application of basic science to coronary
      artery disease.

PMID- 12227524
TI  - New advances in the management of acute severe asthma.

PMID- 12227525
TI  - Attitudes of general practitioners to their interactions with pharmaceutical
      companies: a qualitative study.
AB  - OBJECTIVES: To obtain the attitudes of a sample of General Practitioners to their
      interactions with pharmaceutical companies. DESIGN: Semi-structured face to face
      interviews. SETTING: General Practices in the north-west of Ireland. RESULTS:
      General Practitioners do not value their interactions with pharmaceutical
      representatives. They regard it as promotional, not educational activity and
      believe they are presented with biased information. Positive aspects (social, and
      receiving information) do not compensate. The content of educational meetings
      should be decided by G.Ps. alone. More directly promotional meetings are valued
      less, except when fairly lavish, in which case they are harder to resist.
      Material received through the post is not valued at all by G.Ps. CONCLUSIONS:
      Pharmaceutical companies in Ireland have a good relationship with G.Ps. It is in
      jeopardy. To rescue it, companies need to provide G.Ps. with assistance
      (information and other types) which is directly helpful to G.Ps. caring for their
      patients. Companies need to row back on the deluge of promotional material that
      G.Ps. are faced with. G.Ps. need to be trained to learn how to demand more
      helpful material from companies, and to refuse the promotional tidal wave.

PMID- 12227527
TI  - Incidence of cervical dyskaryosis in Ireland: report of a five-year audit.
AB  - The implementation of a national cervical screening programme in Ireland will
      require agreement on achievable standards in reporting cervical cytology similar
      to those published by the NHS cervical screening programme. Due to the
      opportunistic nature of screening in the Republic of Ireland, national incidence
      figures for uterine cervical disease are not available. An audit of our practice
      was performed to find the incidence of human papilloma virus related cervical
      disease in our population. Our laboratory reported 158,066 cases from 1996-2000.
      The overall rate of dyskaryosis increased from 3.6% to 7.9%, mostly due to
      increased low grade dyskaryosis (up from 2.3% to 6.0%). High grade dyskaryosis
      also increased (from 1.3% to 1.9%), particularly in the under-25 year age group
      who account for a growing proportion of high grade dyskaryosis (from 15.4% of all
      high grade diagnoses in 1996 to 23.0% in 2000). The positive predictive value of
      a diagnosis of high grade dyskaryosis remained stable between 76.0 and 79.5%.
      While opportunistic screening data may not be directly applicable to the entire
      screening population it is hoped that these data may form a foundation on which
      to estimate national incidence figures and define achievable standards for
      cervical screening cytology in Ireland.

PMID- 12227526
TI  - Bronchitis symptoms in young teenagers who actively or passively smoke
      cigarettes.
AB  - This study was undertaken to examine the prevalence of bronchitis (cough with
      phlegm) symptoms in teenagers who either smoked cigarettes on a regular basis
      (active smokers) or were non-smokers but who are exposed to passive smoking
      (passive smokers) in the home. The study was undertaken in 1995 and repeated in
      1998. The 1995 study was a cross sectional questionnaire survey of smoking habits
      in secondary school children aged 13-14 years and was undertaken as part of the
      ISAAC questionnaire survey. Thirty representative and randomly selected schools
      from throughout the Republic of Ireland took part in the study. In the 1995
      study, 3066 students completed a questionnaire on their current smoking habits
      and symptoms of cough and phlegm. We found that 634 (20.7%) of these young
      teenagers actively smoked cigarettes with significantly more females smoking than
      males with 23.3% of girls compared to 17.6% boys (p = 0.0001). We found that
      46.3% of non-smoking children were exposed to smoking in the home (passive
      smokers) with parental smoking accounting for most of the passive smoking.
      Bronchitis symptoms were more commonly reported in active smokers compared to non
      smokers with an odds ratio of 3.02 (95% CI 2.34-3.88) (p < 0.0001) or in passive
      smokers compared to those not exposed to smoking with odds ratio of 1.82 (95% CI
      1.32-2.52) (p < 0.0001). The 1998 study showed similar results for smoking
      habits, passive smoking and prevalence of bronchitis symptoms as with the 1995
      study. These results document that increased bronchitis symptoms occur in
      teenagers exposed to active or passive smoking.

PMID- 12227528
TI  - "Why are we working so hard?" A cross-sectional survey of factors influencing GP
      workload in the Eastern Regional Health Authority area.
AB  - There is increasing evidence to suggest that the subjective workload of GPs in
      Ireland is too heavy. The aims of this study, therefore, were to identify the
      social and demographic issues that GPs perceive as being implicated in
      determining their workload. A self-administered questionnaire, inviting GPs to
      score a series of factors according to the degree to which it increased their
      workload, was sent to one-quarter of GPs practising in the Eastern Regional
      Health Authority (ERHA) area. The response rate was 71%. Seventy-nine (60%) felt
      their workload was 'too heavy,' while 109 (85%) felt they could improve the
      quality of care they provide, if their workload was reduced. Access to OPD
      services (mean score = 7.31), access to other hospital services (mean score =
      7.16), and the number of elderly patients (mean score = 6.28) were considered to
      be the most important factors in determining workload. This paper describes the
      factors that impact on self-perceived workload for GPs, factors which need to be
      considered when planning and funding future developments in primary care.

PMID- 12227529
TI  - Ireland, the UK and Europe: a review of undergraduate medical education in
      palliative care.
AB  - Palliative Care is an important and emerging medical speciality, formally
      recognised by the Irish Medical Council in June 1995. Three years previously, in
      1992, the Association of Palliative Medicine for Great Britain and Ireland
      published an official curriculum for undergraduate medical education in
      palliative care. The European Association of Palliative Care held a workshop the
      following year and reported that, with the exception of the UK, education for
      medical students is incomplete. This review examines the evidence that European
      undergraduate medical education in palliative care is underdeveloped. Key
      elements of effective undergraduate teaching programmes in this discipline are
      identified. Finally, it is noted that little has been written about undergraduate
      palliative care education in Irish medical schools; the situation in this country
      is thus unknown. A study to determine current education in palliative care in
      Irish medical schools is required.

PMID- 12227531
TI  - Small bowel phytobezoar--a rare delayed complication of radiotherapy.

PMID- 12227530
TI  - Troponin.

PMID- 12227533
TI  - Production and characterization of pyrolysis liquids from sunflower-pressed
      bagasse.
AB  - Pyrolysis experiments on sunflower (Helianthus annus L.)-pressed bagasse were
      performed in a fixed-bed tubular reactor. The effects of nitrogen flow rate and
      final pyrolysis temperature on the pyrolysis product yields and chemical
      compositions were investigated. The maximum bio-oil yield of 52.10 wt.% was
      obtained in a nitrogen atmosphere with flow rate of 50 ml min(-1) and at a
      pyrolysis temperature of 550 degrees C with a heating rate of 5 degrees C s(-1).
      The chemical characterization results showed that the oil obtained from sunflower
      pressed bagasse may be a potentially valuable source as fuel or chemical
      feedstocks.

PMID- 12227532
TI  - Composting of a crop residue through treatment with microorganisms and subsequent
      vermicomposting.
AB  - Preliminary studies were conducted on wheat straw to test the technical viability
      of an integrated system of composting, with bioinoculants and subsequent
      vermicomposting, to overcome the problem of lignocellulosic waste degradation,
      especially during the winter season. Wheat straw was pre-decomposed for 40 days
      by inoculating it with Pleurotus sajor-caju, Trichoderma harzianum, Aspergillus
      niger and Azotobacter chroococcum in different combinations. This was followed by
      vermicomposting for 30 days. Chemical analysis of the samples showed a
      significant decrease in cellulose, hemicellulose and lignin contents during pre
      decomposition and vermicomposting. The N, P, K content increased significantly
      during pre-decomposition with bioinoculants. The best quality compost, based on
      chemical analysis, was prepared where the substrate was treated with all the four
      bioinoculants together followed by vermicomposting. Results indicated that the
      combination of both the systems reduced the overall time required for composting
      and accelerated the composting of ligno-cellulosic waste during the winter season
      besides producing a nutrient-enriched compost product.

PMID- 12227534
TI  - Effect of pretreatments of three waste residues, wheat straw, corncobs and barley
      husks on dye adsorption.
AB  - The removal of dyes (Cibacron Yellow C-2R, Cibacron Red C-2G, Cibacron Blue C-R,
      Remazol Black B and Remazol Red RB) from an aqueous solution has been discussed
      by adsorption which was examined on three different low cost pretreated
      agricultural residues viz., wheat straw, corncob and barley husk. The
      pretreatments were carried out in order to delignify, or to increase the surface
      area of the sorbents, and to study their effect on the rate and effective
      adsorption of dyes. Steam, alkali, ammonia steeping and milling were the
      pretreatments employed and compared with the untreated sorbents. A higher
      percentage of dye removal was achieved at a faster rate by the milled samples
      proving milling to be a better and more cost effective treatment, except for
      barley husk which had a higher percentage removal for the control.

PMID- 12227535
TI  - Single-cell protein production from ram horn hydrolysate by bacteria.
AB  - Ram horns obtained from the slaughterhouse of Erzurum, Turkey were hydrolyzed by
      treating with acid (6N-HCl) and ram horn hydrolysate (RHH) was obtained. The
      hydrolysate was used as substrate to grow Bacillus cereus NRRL B-3711, Bacillus
      subtilis NRRL NRS-744 and Escherichia coli in batch system at 30 degrees C; air
      1.5 v/v/min; stirring 150 rpm. Both RHH and biomass samples were analyzed. The
      bacterial cells produced in this hydrolysate were found to be rich in total
      protein (66%, 68% and 71% for E. coli, B. cereus and B. subtilis, respectively).
      The chemical oxygen demand and biological oxygen demand were reduced
      significantly by the growth of bacteria. The protein produced contained all
      essential amino acids for ruminant feed.

PMID- 12227536
TI  - Freundlich adsorption isotherms of agricultural by-product-based powdered
      activated carbons in a geosmin-water system.
AB  - The present study was designed to model the adsorption of geosmin from water
      under laboratory conditions using the Freundlich isotherm model. This model was
      used to compare the efficiency of sugarcane bagasse and pecan shell-based
      powdered activated carbon to the efficiency of a coal-based commercial activated
      carbon (Calgon Filtrasorb 400). When data were generated from Freundlich
      isotherms, Calgon Filtrasorb 400 had greater geosmin adsorption at all geosmin
      concentrations studied than the laboratory produced steam-activated pecan shell
      carbon, steam-activated bagasse carbon, and the CO2-activated pecan shell carbon.
      At geosmin concentrations < 0.07 microg/l for the phosphoric acid-activated pecan
      shell carbon and below 0.08 microg/l for a commercially produced steam-activated
      pecan shell carbon obtained from Scientific Carbons, these two carbons had a
      higher calculated geosmin adsorption than Filtrasorb 400. While the commercial
      carbon was more efficient than some laboratory prepared carbons at most geosmin
      concentrations, the results indicate that when the amount of geosmin was below
      the threshold level of human taste (about 0.10 microg/l), the phosphoric acid
      activated pecan shell carbon and the Scientific Carbons sample were more
      efficient than Filtrasorb 400 at geosmin removal.

PMID- 12227537
TI  - Growth and yield functions for irrigated plantations of Eucalyptus camaldulensis
      in the hot desert of India.
AB  - Eucalyptus camaldulensis forms a major portion of irrigated plantations in the
      hot desert of India and for effective management of these plantations, growth and
      yield functions are necessary. This paper describes the development of height,
      diameter and volume growth functions based on the analysis of the data collected
      from the permanent sample plots laid out in the study area. The Chapman-Richards
      equation could be used for the prediction of diameter growth while the Schumacher
      model could be considered for predicting volume growth. Some base-age variant and
      invariant site-index models, already reported in the literature, were compared in
      terms of relative accuracy and it was found that the Payandeh and Wang model
      performed the best among the four models tried.

PMID- 12227538
TI  - Nitrogen transformations during aerobic/anoxic sludge digestion.
AB  - Laboratory experiments were conducted to study and compare nitrogen
      transformations occurring under both aerobic digestion and aerobic/anoxic (A/A)
      digestion. The process performance was examined at different sludge residence
      times (SRTs), temperatures and anoxic cycles. Both modes of operation gave
      comparable solids reduction results. However, introduction of anoxic periods to
      aerobic sludge digestion appears to be a promising alternative to control pH
      during digestion through endogenous nitrate respiration (ENR). Operating an
      aerobic digester with an anoxic phase to achieve complete denitrification would
      also improve supernatant quality over that achieved solely by aerobic digestion.
      Alternating A/A operation can conserve most of the influent alkalinity and
      maintain near neutral pH condition over prolonged periods. The A/A digestion of
      mixed primary/waste-activated sludge achieved up to 43.7% reductions in volatile
      suspended solids, 33.7% removal of total nitrogen, and a specific ENR rate of
      5.75 x 10(-2) mg NO3-N/mg VSSd. Optimum results were obtained at 10 d SRT, 30
      degrees C temperature, and 50% anoxic cycle length.

PMID- 12227539
TI  - Biosorption of chromium(VI) from aqueous solution by cone biomass of Pinus
      sylvestris.
AB  - Biosorption of chromium(VI) on to cone biomass of Pinus sylvestris was studied
      with variation in the parameters of pH, initial metal ion concentration and
      agitation speed. The biosorption of Cr(VI) was increased when pH of the solution
      was decreased from 7.0 to 1.0. The maximum chromium biosorption occurred at 150
      rpm agitation. An increase in chromium/biomass ratio caused a decrease in the
      biosorption efficiency. The adsorption constants were found from the Freundlich
      isotherm at 25 degrees C. The cone biomass, which is a readily available
      biosorbent, was found suitable for removing chromium from aqueous solution.

PMID- 12227540
TI  - Utilization of the coconut shell of babacu (Orbignya sp.) to produce cement
      bonded particleboard.
AB  - This experiment evaluated the use of the material of the outer coconut shell of
      babacu (Orbignya sp.), a palm tree from Brazil, for the manufacture of
      particleboards bonded with Portland cement. Four treatments were analyzed at two
      target densities (1.2 g/cm3 and 1.4 g/cm3) and two levels (0% and 4%) of addition
      of calcium chloride. The lignocellulosic material from babacu presented a low
      cement inhibition index according to the hydration test. Testing of manufactured
      panels showed that good physical and mechanical properties were achieved at the
      treatment levels tested.

PMID- 12227541
TI  - Biosorption of phenol from an aqueous solution by Aspergillus niger biomass.
AB  - Phenols in trace quantities are usually present in the treated effluent of many
      wastewater-treatment plants. Phenol contamination of drinking water even at 1
      microg/l concentration can cause significant taste and odor problems. This study
      investigates the use of non-viable pretreated cells of Aspergillus niger to
      remove phenol from an aqueous solution. Five types of non-viable pretreated A.
      niger biomass powders were used as a biosorbent to remove phenol present in an
      aqueous solution at a concentration of 1,000 microg/l. Sulfuric acid-treated non
      viable biomass powder, which was the most effective, was used as a biosorbent in
      a further study. The maximum removal of phenol was observed at an initial pH of
      5.1 for the sulfuric acid-treated biomass. The adsorption of phenol by pretreated
      A. niger biomass was best described by the Brunauer Emmet Teller model.
      Desorption of phenol using distilled deionized water was found to be
      approximately 5% suggesting a strong biosorption by the biomass. Sulfuric acid
      treated biomass beads developed through immobilization in polysulphone were used
      in a column study. Approximately 66% of phenol was removed in the column operated
      at an initial pH of 5.1 and an initial concentration of 1,000 microg/l of phenol.

PMID- 12227542
TI  - Effect of some pulverised plant materials on the developmental stages of fish
      beetle, Dermestes maculatus Degeer in smoked catfish (Clarias gariepinus) during
      storage.
AB  - The effectiveness of pulverised plant materials; Tithonium diversifolia,
      Afromomum melegueta, Nicotiana tabacum, Monodora myristica and Piper guineense as
      ovicidal, larvicidal and adult deterents of fish beetle (Dermestes maculatus) in
      smoked catfish (Clarias gariepinus) during storage were evaluated. Leaves of T.
      diversifolia, N. tabacum and seeds of A. melegueta, M. myristica and P. guineese
      were dried and pulverised into powder. Adults and larvae of third generation (F3)
      of D. maculatus were introduced into Kilner jars containing disinfested fish
      samples. Pulverised plant materials were applied to the surface of the fish
      samples at 10% (w/w) and monitored for 40 days, while egg hatchability of the
      insects was monitored for seven days. The result showed that all the plant
      materials had varying degree of insecticidal activities. Pulverised powder of P.
      guineense and A. melegueta were the most effective and significantly (P < 0.05)
      inhibited egg hatchability and adult emergence of D. maculatus in smoked catfish.
      N. tabacum gave the lowest insecticidal effect on adults, larvae and eggs of D.
      maculatus. However, the larvae of D. maculatus were not significantly (P > 0.05)
      affected by the plant materials. The percentage weight loss in fish treated with
      P. guineense and A. melegueta were minimal compared with the untreated fish
      sample. The result of this study showed that pulverised plant materials obtained
      from P. guineense and A. melegueta could be used to deter egg hatchability and
      adult emergence of D. maculatus in smoked catfish during storage. This could also
      reduce percentage losses due to insect infestation on smoked fish during storage.

PMID- 12227544
TI  - Separation efficiency and particle size distribution in relation to manure type
      and storage conditions.
AB  - Mechanical separation of liquid animal manure can be an effective technique for
      production of a liquid and a nutrient-rich solid fraction. The efficiency of
      separators depends on the physical and chemical composition of the animal manure.
      Therefore, the particle size composition was measured for different types of
      manure before treatment with a decanting centrifuge and a screw press. Storage of
      pig manure reduces the total dry matter content, and the content of small
      particles (< 0.0016 mm) is reduced more than the content of large particles. In
      consequence, the proportion of large particles will increase, while the portion
      of small particles will decrease. The separation efficiency of the screw press
      was found to be low, as this separator only retains particles > 1 mm. The
      decanter centrifuge retained all the particles > 0.02 mm and was therefore much
      more efficient than the screw press. Separation efficiency was also found to be
      highly dependent on the type of manure used.

PMID- 12227543
TI  - Characteristics, and carbon and nitrogen dynamics in soil irrigated with
      wastewater for different lengths of time.
AB  - Irrigation of agricultural land with wastewater will increase crop production,
      but also heavy metal concentrations and the rate of infection of farmers with
      pathogens. The risks associated with the use of wastewater are reduced by
      treating the wastewater, but treatment also reduces organic material, phosphorus
      and inorganic N for crops. We investigated characteristics, e.g. heavy metal
      concentrations, of soils of the valley of the Mezquital (Mexico) irrigated with
      waste from Mexico City water since 1912, 1925, 1965, 1976, 1996 or 1997, or not
      irrigated at all, and dynamics of C and N when soil was amended with wastewater
      or drainage water. Concentrations of total Mg, Hg, Mo, Ca, Cu and Cr, available
      concentrations of Pb, Cd and Cu increased significantly with length of irrigation
      (P < 0.05), but were not at hazardous concentrations. Although organic C, total
      N, microbial biomass C and N, and microbial activity, as witnessed by CO2
      production, increased with length of irrigation, N mineralization did not.
      Oxidation of NO2- was inhibited and could be due to increases in salinity, toxic
      compounds or heavy metals. We found that N mineralization was low or absent so it
      will not compensate for the loss of N when the wastewater is treated and
      application of N fertilizer will be required to maintain the same level of crop
      production. The characteristics of the soils appear not to have deteriorated
      after years of application of wastewater, but further irrigation even with
      treated wastewater might increase sodicity and salinity and pose a threat to
      future crop production.

PMID- 12227545
TI  - Effect of the application of water hyacinth compost/vermicompost on the growth
      and flowering of Crossandra undulaefolia, and on several vegetables.
AB  - The impact of the application of compost/vermicompost obtained from water
      hyacinth (Eichhornia crassipes, Mart. Solms) on plants was assessed in terms of
      growth and flowering of the angiosperm crossandra (Crossandra undulaefolia).
      Overall nine morphological, size, and yield attributes were studied in crossandra
      saplings raised on water hyacinth compost or vermicompost as compared to the
      untreated saplings. Application of vermicompost led to statistically significant
      improvement in the growth and flowering of crossandra compared to the untreated
      plants. The impact of compost was also beneficial but a little less distinct than
      the positive impact of vermicompost. Qualitative studies were simultaneously
      conducted in five kitchen gardens owned by farmers near Pondicherry. In three of
      these locations water hyacinth vermicompost was applied-and no other fertilizer
      for months to different species of vegetables. Water hyacinth compost was
      similarly applied in another two locations. In all the locations no adverse
      effect on any of the plant species was observed. We believe these studies would
      help in dispelling the apprehension of farmers that compost/vermicompost obtained
      form a pernicious weed like water hyacinth may have deleterious effect on other
      plants.

PMID- 12227546
TI  - Moisture excluding efficiency and dimensional stability of wood improved by
      acylation.
AB  - The dimensional stability and moisture excluding efficiencies (MEEs) of wood
      after acetylation, butyrylation, and hexanoylation, were evaluated in this study.
      After three acylation treatments, an excellent antiswelling efficiency of
      modified wood specimens was obtained. All the equilibrium moisture contents of
      acylated wood at three relative humidities (RHs) (33% RH, 65% RH, and 93% RH)
      were significantly reduced, as compared to those of untreated wood in the same
      RH, and the MEEs of acylated wood were greatly improved. Acylated wood has
      consistent MEE at each of the different RHs. With the same percentage of
      substituted hydroxyl groups, the decreasing order of the MEE of modified wood was
      hexanoylation > butyrylation > acetylation. This indicates that the molecular
      volume or hydrophobic property of the substituted acyl groups also has the
      influence on the MEE of modified wood, in addition to the degree of substitution
      of the hydroxyl groups.

PMID- 12227547
TI  - Activated parthenium carbon as an adsorbent for the removal of dyes and heavy
      metal ions from aqueous solution.
AB  - Parthenium hysterophorous (L) is a perennial weed distributed all over the
      country. Carbonized parthenium activated with conc. H2SO4 and ammonium
      persulphate was effective in the removal of dyes, heavy metals and phenols.
      Variation in the percentage removal of adsorbates was observed with increase in
      the contact time. Among the adsorbates tested, the affinity of the activated
      parthenium carbon was highest for Hg2+, Methylene Blue and Malachite Green.

PMID- 12227548
TI  - Optimisation of a culture medium containing fish silage for L-lysine production
      by Corynebacterium glutamicum.
AB  - In a first step the effects of 10 components of a culture medium designed for L
      lysine production were evaluated with a 2(10-6) factorial design. Among them,
      glucose, fish silage, and ammonium sulphate showed a significant effect. In a
      second step, an orthogonal-central composite experimental design and response
      surface methodology was performed with five from the 10 initial compounds. The
      determination coefficient (R2) of the fitted second-order model was 0.990. L
      lysine production with the optimised medium increased 2.6 times as compared with
      the original medium.

PMID- 12227550
TI  - Origins of material contrast in scanning ion microscope images.
AB  - A Monte Carlo simulation of ion-induced kinetic electron emission (KE) was
      carried out to study the material contrast in scanning ion microscope (SIM)
      images, i.e. secondary electron (SE) yields decreasing with atomic number Z2 of
      the target, which is opposite to that for scanning electron microscope (SEM)
      images. The simulations show that SE yields decrease with increasing Z2 for the
      targets of Al (Z2 = 13), Cu (Z2 = 29) and Au (Z2 = 79) bombarded by 10
      approximately 40 keV gallium (Ga) ions. Details of the SE yield according to the
      collision partners (i.e. Ga ion, recoiled target-atom and excited electron)
      clarify the origins of material (or Z2) contrast in the Ga-SIM images. Cause and
      effect on the material contrast are as follows: the heavier (or slower) collision
      partner transfers less energy to the excited electrons and leads to a poorer
      multiplication of other excited electrons in the cascade process. The simulation
      also predicts that the Ga-SIM images are more sensitive to the outermost target
      surface than the SEM images. material contrast, atomic number contrast, secondary
      electrons, secondary electron yield, scanning ion microscope, scanning electron
      microscope

PMID- 12227549
TI  - Effects of root-dip treatment with certain phosphate solubilizing microorganisms
      on the fusarial wilt of tomato.
AB  - Root-dip application of Bacillus subtilis, Pseudomonas fluorescens, Aspergillus
      awamori, Aspergillus niger and Penicillium digitatum resulted in significant
      decline in the rhizosphere population of Fusarium oxysporum f. sp. lycopersici. A
      significant decrease in the severity of wilt occurred with A. awamori (37.1%) and
      P. digitatum (21.3%) compared to the control. Root-dip treatment with the
      phosphate solubilizing microorganisms tested resulted in significant increase in
      the yield of tomato, being greatest with A. awamori and P. digitatum in pathogen
      inoculated (36% and 33%) and uninoculated plants (19% and 23%). A chemical
      fungicide gave 24% better yield.

PMID- 12227551
TI  - New characterization method for pore and packing structure in powder compacts
      using confocal laser scanning microscope.
AB  - The internal structure of powder assemble was observed by a confocal laser
      scanning microscope and the results were compared with those of other
      conventional methods. Two kinds of specimens were examined in this paper: powder
      compacts from alumina granules and set plaster of gypsum. The structure was
      sensitive to humidity during pressing of the granule compact of alumina
      containing polyvinyl alcohol as a binder. Narrow interstices were noted along the
      boundaries of granules in low humidity. However, uniform internal structure was
      noted in high humidity. The origin of the difference of packing structure was
      attributed to the change of binder characteristics with humidity. Interstices
      were formed in low humidity due to poor adhesion of binder and spring back after
      pressure removal. The superior capability of the present characterization
      technique can distinguish a minor difference of internal structure successfully.

PMID- 12227552
TI  - Observation of magnetic domain structure in phase-separated manganites by lorentz
      electron microscopy.
AB  - Magnetic domain structure in manganites was investigated by Lorentz electron
      microscopy, in order to understand some unusual physical properties, such as a
      colossal magnetoresistance (CMR) effect and a metal-to-insulator (MI) transition.
      In particular, we examined the spatial distribution of the charge/orbital ordered
      (CO/OO) insulator state and the ferromagnetic (FM) metallic state in phase
      separated manganites, (La5/8-xPrx)Ca3/8MnO3 for x = 0.375, by obtaining both the
      dark-field and Lorentz images. We found an unusual coexistence of the CO/OO and
      FM metallic states with micrometer size below a MI transition temperature of 60
      K. Our experimental findings provide direct evidence of the phase separation
      found in CMR manganites.

PMID- 12227553
TI  - Combination of electron microscopic in situ hybridization and anti-DNA antibody
      labelling reveals a peculiar arrangement of ribosomal DNA in the fibrillar
      centres of the plant cell nucleolus.
AB  - The fibrillar centres (FCs) in the nucleoli of Allium cepa usually contained
      compact dense chromatin, which was always surrounded with light fibrous material
      (LFM). Distribution of 18S ribosomal DNA (rDNA) in the FCs was examined by in
      situ hybridization at the light and electron microscopic levels and the results
      were compared with those obtained by immunogold labelling with anti-DNA
      antibodies. Anti-DNA antibodies heavily labelled the dense chromatin of the FCs
      but scarcely labelled the LFM. However, electron microscopic in situ
      hybridization using the 18S rDNA probe showed that the label in the dense
      chromatin was extremely weak compared with that obtained by the anti-DNA antibody
      labelling: the specific label with anti-DNA antibodies of the dense chromatin was
      about 15 times as much as that of the LFM, whereas the specific label with in
      situ hybridization in the dense chromatin was only about 1.7 times higher than in
      the LFM. These results suggest that the rDNA encoding rRNA is preferentially
      released from the dense chromatin and that non-transcribed intergenic spacers
      remain in the dense chromatin as the anchoring sites of rDNA.

PMID- 12227554
TI  - Imaging saponin-induced structural changes in neural processes with atomic force
      microscopy.
AB  - Temporal changes in the structure of neuronal processes in the presence of
      saponin were studied by atomic force microscopy in a fluid medium. After saponin
      treatment, concavities were formed on the surface of some neurites and fibrous
      structures in other neurites were splayed. The vertical height of these splayed
      fibrils or fibrillar bundles ranged from 13 to 370 nm, and the horizontal width
      was less than 500 nm. These findings suggest that formation of concavities and
      separation of bundled fibrils occurred simultaneously in saponin-treated
      neurites.

PMID- 12227555
TI  - Morphological changes of Candida albicans induced by micafungin (FK463), a water
      soluble echinocandin-like lipopeptide.
AB  - Micafungin (FK463), a novel water-soluble echinocandin-like lipopeptide, exerted
      fungicidal action toward growing cells of Candida albicans at concentrations of
      0.1 microg ml(-1) or above. The drug at these levels induced osmotically fragile
      cells and the resulting fungicidal effect was partially reversed when cultures
      were grown in the presence of an osmotic stabilizer. Candida cells incubated with
      fungicidal concentrations of micafungin gradually increased in size and/or became
      deformed. An electron microscopic study of such micafungin-treated cells revealed
      morphological alterations in the cell wall; deformation in contour, abnormal
      septum formation and decrease in thickness of the intermediate layer of the cell
      wall were prominent. In addition, the structure of cell membranes as well as of
      membranous cytoplasmic organelles was slightly impaired. These data suggest that
      micafungin principally affects the normal formation of the cell wall in growing
      Candida cells.

PMID- 12227556
TI  - How to make mapping images of biological specimens--data collection and image
      processing.
AB  - To make high-quality elemental mapping images of biological specimens, the
      conditions of data collection were optimized, and image-processing methods were
      examined. The most important step was to obtain a sufficient number of electrons
      to make the images. The exposure time was limited by the characteristics of the
      CCD camera. Obtaining a long exposure time exceeded the limitations of the
      camera, so exposures of the same area were performed many times and recorded in
      many images. The divided images were merged after observation. To merge images, a
      new software, 'Rotate & Merge' (R&M), was developed. Because of the
      characteristics of biological specimens, R&M must have several functions. Picture
      zoom and image rotation are necessary because of shrinkage of the specimens due
      to irradiation during exposure, since even cryo techniques, including low-dose
      techniques, do not prevent shrinkage of specimens. Merged phosphorus-mapping
      images of ultra-thin slices of yeast cells were made. In these images, ribosome
      particles and DNA in the nucleus were observed clearly. The merging was very
      useful for improving the quality of mapping images.

PMID- 12227557
TI  - Detection of aluminium by energy dispersive X-ray microanalysis at high
      accelerating voltages with semi-thin sections of biological sample.
AB  - Aluminium (Al) was detected in semi-thin sections of three organs, the duodenum,
      liver and kidney, of ddY strain mouse by energy dispersive X-ray microanalysis at
      high accelerating voltages around 300 kV. Firstly, to determine the conditions
      best for detecting Al, several adult ddY mice were injected intraperitoneally
      with aluminium chloride (AlCl3) and the duodenums were fixed, embedded and
      sectioned at various thicknesses and subjected to energy dispersive X-ray
      microanalysis at various accelerating voltages from 100 to 400 kV. From the
      results obtained, 1.0 microm-thick sections observed at 300 kV resulted in the
      highest peak-counts/background ratios and were shown to be the most suitable for
      X-ray microanalysis. Secondly, ddY mice aged four weeks were administered orally
      with 2% AlCl3 at pH 2.5 for two weeks and the three organs (duodenum, liver and
      kidney) were subjected to X-ray microanalysis under the same condition found
      above. The results were compared with light microscopic Al staining of the same
      tissues. Aluminium was detected in lysosomes of the three kinds of tissues with
      higher sensitivity by energy dispersive X-ray microanalysis by light microscopic
      observation. From the results, it was suggested that Al dissolved in acidic water
      was absorbed in the duodenum and accumulated in the liver and kidney.

PMID- 12227558
TI  - Glomerular podocyte endocytosis of the diabetic rat.
AB  - We used immunoelectron microscopy to examine whether glomerular podocytes have
      the endocytotic function of macromolecular proteins in the early stage of
      diabetic nephropathy. Diabetes was induced by injecting streptozocin 60 mg kg wt(
      1) into rats. Creatinine clearance but not urinary protein excretion was
      increased after four weeks of diabetes. The kidneys were morphologically studied
      1 h after goat serum injection. In conventional electron microscopy, lysosomes
      were conspicuous in the podocytes of diabetic rats. Immunoelectron microscopy
      revealed that endogenous rat IgG and exogenous goat IgG were present in the
      lysosomes of podocytes from diabetic rats. The results indicated that the
      podocytes had an increased capacity for endocytosis in the early stage of
      diabetic nephropathy without increased urinary protein excretion.

PMID- 12227559
TI  - Breastfeeding: reasons for starting, reasons for stopping and problems along the
      way.
AB  - The objective of this study was to describe the problems experienced by mothers
      when breastfeeding and the impact that these problems have on breastfeeding
      duration. A cohort of 556 mothers who birthed in Perth, Western Australia were
      recruited to study their infant feeding practices. The mothers were interviewed
      in hospital and again at 2, 6, 10, 14, 18 and 24 weeks postpartum, or until they
      ceased to breastfeed. The results showed that most mothers were not prepared to
      experience any difficulties or problems with breastfeeding. Twelve percent of the
      mothers left hospital without having attempted to breastfeed. The most common
      reasons given for infant-formula-feeding related to previous problems with
      breastfeeding, the ability of husbands to assist with feeding and perceived ease
      of bottle-feeding. While in hospital 83% of breastfeeding women stated that they
      had experienced one or more problems related to breastfeeding. Two weeks after
      leaving hospital 29% of breastfeeding mothers were experiencing problems and the
      prevalence of problems continued to decline, reaching 13% at six months. In this
      study the most common reason cited by mothers for stopping breastfeeding before
      the baby was two weeks old, was that their baby was unsettled, a behaviour often
      interpreted by mothers as indicating an insufficient milk supply. Levels of
      anxiety over milk supply reached 23% in the early stages of breastfeeding, and a
      number of mothers were still experiencing anxiety through to six months. Anxiety
      over the sufficiency of breastmilk supply was the most serious problem, in that
      it often resulted in the cessation of breastfeeding Most mothers experience some
      problems during breastfeeding, especially in the early stages. Proper advice and
      management is required to ensure that the problems do not lead to cessation of
      breastfeeding.

PMID- 12227560
TI  - Using pacifiers: what are breastfeeding mothers doing?
AB  - The objective of this study was to identify the impact of pacifier use on the
      duration of breastfeeding amongst Australian women. A cohort of 556 mothers who
      delivered in Perth, Western Australia was recruited to study their infant feeding
      practices. The mothers were interviewed in hospital and again at 2, 6, 10, 14, 18
      and 24 weeks postpartum, or until they ceased to breastfeed. At two weeks 62% of
      breastfed babies were using a pacifier, increasing to a peak of 78% at six weeks.
      Infants who were using a pacifier had slightly fewer feeds each day at every age
      period (for example 6.9 versus 7.4 feeds at six weeks of age), but there was no
      difference in the number of night feeds. A recent study suggested that the
      mothers resorted to the use of pacifiers when they were having problems
      breastfeeding, and any impact of pacifiers on breastfeeding duration was due to
      confounding factors. However in this longitudinal study, after adjusting for the
      presence of breastfeeding problems, the use of a pacifier at two weeks was
      associated with reduced likelihood of breastfeeding to six months (odds ratio
      0.40; 95%CI 0.25-0.63). Based on the results of this study we concluded that the
      use of a pacifier at two weeks of age reduced the likely duration of
      breastfeeding to six months. A possible mechanism of action was the reduced
      number of daily feeds in breastfed infants that would reduce breast stimulation.
      If mothers choose to use a pacifier they should introduce it later and use it
      infrequently.

PMID- 12227561
TI  - Initial infant feeding decisions and duration of breastfeeding in women from
      English, Arabic and Chinese-speaking backgrounds in Australia.
AB  - Anecdotally, concerns are often expressed about the varying infant feeding
      decisions among women from different cultural groups. This paper reports the
      early infant feeding decisions and duration of breastfeeding in 986 women from
      English, Chinese and Arabic-speaking backgrounds in Sydney during 1997 and 1998.
      Data were collectedfrom an audit of medical records and through a questionnaire
      at eight weeks postpartum. Chinese-speaking women were less likely to express an
      intention to breastfeed and fewer initiated breastfeeding compared with other
      women. Arabic-speaking women had significantly longer duration rates compared
      with other women. A greater proportion of the Chinese-speaking women who
      initiated breastfeeding were still breastfeeding at eight weeks compared with
      English-speaking women. This study suggests that there are differences in the
      infant feeding decisions between English, Arabic and Chinese-speaking women.
      Clinicians need to further understand cultural differences when providing care,
      education and support in a multicultural context.

PMID- 12227562
TI  - The path of determination: exploring the lived experience of breastfeeding
      difficulties.
AB  - Breastfeeding is the method of choice for infants and most women support the
      statement that 'breast is best'. Although the majority of Australian women do
      initiate breastfeeding, many also encounter difficulties in what they assume to
      be an easy, natural process. Additionally, a number of women face difficulties
      significant enough to warrant additional support from resources such as the
      Breastfeeding Centre of Western Australia. Managing these difficulties influences
      mothers' perceptions of their breastfeeding experiences. However, the stories of
      these women have not been addressed in the literature. This phenomenological
      study explored the lived experiences of mothers with breastfeeding difficulties,
      who presented to the Breastfeeding Centre of Western Australia. In-depth
      interviews with ten women revealed three main themes: 'path of determination,
      'staying on the path; and 'coming off the path'. The study contributes to the
      body of knowledge on infant feeding and provides insight to health care
      professionals working with breastfeeding women.

PMID- 12227563
TI  - Spiers memorial lecture dynamics of surface reactions.
AB  - The dynamics of electrode processes is discussed in the framework of the general
      hierarchy of dynamic processes underlying interface reactions. On the quantum
      level, the energy transfer between the various degrees of freedom of a reacting
      system may now be studied by ultrafast (femtosecond) laser techniques. On the
      atomic level the mechanism of surface reactions may be investigated by STM and
      spectroscopic methods. Frequently a surface reaction will affect the structure of
      the substrate on the mesoscopic scale. The kinetics of such phase transformations
      proceeds either by a nucleation and growth mechanism or by spinodal
      decomposition. The latter can be studied in electrodissolution by combining STM
      with very short potential pulses. In this context, a novel technique for
      electrochemical micromachining is presented. Finally, some aspects of nonlinear
      kinetics on the macroscopic level associated with spatio-temporal pattern
      formation are briefly discussed.

PMID- 12227564
TI  - Cadmium underpotential deposition on Cu(111) in situ scanning tunneling
      microscopy.
AB  - Atomically resolved in situ STM images are presented for an underpotentially
      deposited (upd) cadmium layer on a Cu(111) electrode from a 10(-4) M CdCl2/10(-2)
      M HCl solution. The observed moire-like structure seen in the images is analysed
      by means of an algebraic model for this long-range superstructure. A structure
      model for the upd layer is developed which reflects all features of the observed
      moire pattern. Furthermore the height modulation was simulated by a hard-sphere
      model for the Cd overlayer and shows remarkable agreement with the detailed
      tunneling current density distribution of the measured STM images. The existence
      of translational and rotational domains is demonstrated. The results are also
      compared and shown to be fully consistent with previous (ex situ) low-energy
      electron diffraction (LEED) observations of this system. The mechanism of Cd upd
      involves a dynamic site exchange between preadsorbed Cl- anions and adsorbing
      Cd2+ cations as previously concluded from ex situ X-ray photoelectron (XPS) and
      low-energy ion scattering (LEIS) measurements.

PMID- 12227565
TI  - Waveguide surface plasmon resonance studies of surface reactions on gold
      electrodes.
AB  - We describe the fabrication and characterisation of gold-coated graded index
      channel waveguide sensors designed for simultaneous electrochemical and surface
      plasmon resonance studies. The active sensing electrode area is a thin gold film
      between 0.5 and 5 mm in length and 200 microm wide deposited on top of a 3 microm
      wide waveguide which forms one arm of a Y-junction while the other arm of the Y
      junction serves as a reference. Using these devices we have measured
      simultaneously the changes in transmittance through the device whilst carrying
      out cyclic voltammetry in either sulfuric or perchloric acid solution or during
      the deposition of an UPD layer of copper at the gold surface. In all cases we
      obtain stable and reproducible results which demonstrate the very high
      sensitivity of the devices to sub-monolayer changes occurring at the gold
      electrode surface. The response of these integrated optoelectrochemical devices
      is discussed in terms of a numerical model for the propagation of light within
      the waveguide structure.

PMID- 12227566
TI  - Organic compound adsorption on Au(111): simultaneous SHG/electrochemical studies.
AB  - Camphor has attracted considerable attention in electrochemical research because
      it adsorbs strongly on metal surfaces. Due to its surface activity it is able to
      inhibit surface reactions. Recently, camphor has been used in investigations of
      nonlinear surface dynamics and pattern formation. Details regarding its influence
      on the morphology of the metal surface, the significance of surface
      reconstruction, structural changes in the camphor adlayer and oxide formation
      remain unclear. We employ second harmonic generation (SHG) to elucidate the
      structural and electronic behaviour of Au(111) surfaces during camphor adsorption
      and desorption processes. Our technique allows measurement of the anisotropy of
      the SHG intensity while simultaneously performing cyclic voltammetry (CV) using
      the hanging meniscus configuration. The anisotropy data can be refined, yielding
      the symmetry components of the second order susceptibility tensor chi2 which are
      analysed as a function of external potential and related to the system's
      electrochemical behaviour. Results of SHG measurements are presented together
      with corresponding CV data and discussed with respect to the open questions
      mentioned above.

PMID- 12227567
TI  - An FTIR study of the surface chemistry of the dynamic Si(100) surface during
      etching in alkaline solution.
AB  - In situ FTIR spectroscopy has been used in the attenuated total reflectance (ATR)
      mode to investigate the surface chemistry of etching Si(100) surfaces in aqueous
      KOH. The effect of solution concentration and electrode potential on the Si-H
      vibrations has been explored and the experimental results compared with density
      functional theory calculations. In addition. the kinetics of surface passivation
      of n-Si(100) has been investigated using FTIR spectroscopy.

PMID- 12227568
TI  - Effect of local environment on nanoscale dynamics at electrochemical interfaces:
      anisotropic growth and dissolution in the presence of a step providing evidence
      for a schwoebel-ehrlich barrier at solid/liquid interfaces.
AB  - The dynamics of nanoscale islands in the vicinity of a monoatomic step on a metal
      electrode surface under potential control have been investigated by potential
      pulse perturbation time-resolved scanning tunneling microscopy (P3 TR-STM). As
      the metastable islands decay, a clear anisotropy develops in the spatial
      distribution of islands, relative to the monoatomic step. Islands appear to be
      stabilized above the step, while a denuded region develops below the step over a
      distance of about 100 nm. Vacancy islands are observed to be more stable than
      adatom islands. These results provide evidence for an electrochemical Schwoebel
      Ehrlich barrier to diffusion of atoms across the step.

PMID- 12227569
TI  - Structure and dynamics of the interface between a Ag single crystal electrode and
      an aqueous electrolyte.
AB  - The aim of this work is to elucidate the initial steps of the electrochemical
      oxidation of Ag(111) in alkaline electrolytes. We use electrochemical as well as
      ex situ (XPS) and in situ (SHG) spectroscopic techniques to reconstruct the
      Ag(111)/electrolyte interface as a complex dynamic entity. Moving in the
      direction from negative to positive potentials we first observe specific
      adsorption of hydroxide ions, which starts at ca. -1.1 V vs. Ag/Ag2O in 0.1 M
      NaOH. SHG data prove that hydroxide retains its negative charge. At -0.3 V
      oxidation of the surface sets in with the formation of negatively charged
      adsorbed oxygen species and Ag+ ions, which give rise to peaks at 528.2 +/- 0.2
      eV and at 367.7 eV in the O 1s and the Ag 3d(5/2) XP spectra, respectively.
      Around -0.1 V the adlayer is transformed into an ordered surface oxide phase
      which grows via a nucleation and growth mechanism. Above the reversible Ag/Ag2O
      potential the 2D Ag(I) oxide transforms into a 3D Ag(I) oxide. The
      electrochemical oxidation is compared with the previously studied gas-phase
      process, demonstrating both remarkable similarities as well as some differences.

PMID- 12227570
TI  - Visualization and characterization of electroactive defects in the native oxide
      film on aluminium.
AB  - Spatial!y localized electrochemical activity at Al/Al2O3 electrodes has been
      investigated using scanning electrochemical microscopy (SECM) in order to
      establish the relationship between localized corrosion of Al (and Al alloys) with
      the defect structure of the native Al2O3 film. Local electron transfer at
      microscopic defects (2 to 50 microm radius) was visualized in acetonitrile
      solutions using the nitrobenzene/nitrobenzene radical anion (Eo approximately 
      1.6 V vs. Ag/Ag+) and tetracyanoquinodimethane/tetracyanoquinodimethane radical
      anion couples (Eo approximately -0.3 V) as redox mediators for imaging. SECM
      investigations revealed no significant differences in electrochemical activity at
      Al/AI203 electrodes in the two mediator solutions, indicating that electrical
      conduction at the defect sites is weakly dependent on interfacial potential and
      the electric field across the Al2O3 film. The density of electroactive defects
      observed by SECM varied by 2 to 3 orders of magnitude between electrodes prepared
      from the same source of Al (either 99.450% and 99.9995%) suggesting that
      electrical conduction in the native oxide is very sensitive to surface
      preparation. Defect densities as low as approximately 3 sites cm(-2) were readily
      measured by SECM.

PMID- 12227571
TI  - Single crystal experiments on grains of polycrystalline materials: oxide
      formation on Zr and Ta.
AB  - Passivation on polycrystalline Zr (hcp) and Ta (bcc) depends on the
      crystallographic orientation of the individual grains, determined by electron
      back scattering diffraction (EBSD). Microelectrochemical experiments yield
      characteristic data, such as oxide formation potentials, formation factors,
      capacities, and thicknesses, of local oxide formation on single grains. Strong
      differences occur on Zr, for Ta only a small influence of crystallographic
      orientation is observed. The rate of oxide formation, determined from
      potentiodynamic and capacitive measurements, and EBSD pattern quality, increases
      with decreasing surface atom density. The dominating influence can be described
      by the Euler angle phi, the second angle phi2 has a smaller influence. The
      differences in surface atom density lead to a specific current-dependent
      potential drop during oxide growth and therefore to a shift in the oxide
      formation potential. Furthermore the crystallinity and epitaxy of the oxides can
      depend on the orientation of the base metal causing a variation in ion
      conductivity.

PMID- 12227572
TI  - The influence of anions and kink structure on the enantioselective electro
      oxidation of glucose.
AB  - The electro-oxidation of glucose in sulfuric acid using well-defined chiral
      platinum single crystal electrodes has been demonstrated previously to be an
      enantioselective reaction with the degree of enantioselectivity being dependent
      on the surface density of kink sites. The chirality of the surface originates
      from the microstructure of the kink site whereby the sequence of the three
      fundamental adsorption sites [111], [100] and [110] constituting the kink may be
      viewed from the electrolyte phase either in a clockwise (R-enantiomer) or anti
      clockwise (S-enantiomer) fashion. In the present study, this work is extended to
      examine the role of both kink structure and specifically adsorbed anions on the
      mechanism of chiral discrimination. Kinked surfaces based on [111] terraces
      (Pt[976],Pt[643] and Pt[531]),[100] terraces (Pt[721]) and [110] terraces
      (Pt[11,7,1] and Pt[841]) have been investigated and both the magnitude and
      potential dependence of the enantioselective electro-oxidation of glucose
      characterised. Additionally, the changes engendered by interchanging the
      character of the two steps whose confluence form the kink whilst maintaining the
      symmetry of the terrace has also been examined via a comparison of Pt[643] and
      Pt[431]. Low energy electron diffraction (LEED) was used to confirm that all
      surfaces when clean and thermally annealed were in their (1 x 1) state. Cyclic
      voltammetry (CV) confirmed this finding for flame-annealed electrodes after
      cooling in hydrogen. Three general points emerge from the electro-oxidation
      studies: (i) The highest degree of enantioselectivity is exhibited by kink sites
      adjacent to [111] and [110] terraces in sulfuric acid. (ii) The adsorption of
      specifically adsorbed anions like bisulfate/sulfate influences strongly the
      chiral discriminatory behaviour of all surfaces. (iii) No electro-oxidation takes
      place at [110] sites, as evidenced by complete overlap of the [110] step hydrogen
      underpotential deposition (UPD) charge in glucose and glucose-free solutions.
      Nonetheless it is deduced that [110] sites must play some part in the initial
      orienting of the glucose molecule prior to reaction. Ideas based on these
      findings are developed in order to rationalise in particular the influence of
      anion adsorption on the initial enantioselective interaction of the glucose
      molecule with the chiral surface.

PMID- 12227573
TI  - In situ FTIR studies on the effect of temperature on the electro-oxidation of
      small organic molecules at the Ru(0001) electrode.
AB  - The adsorption and electro-oxidation of formaldehyde, formic acid and methanol at
      the Ru(0001) electrode in perchloric acid solution have been studied as a
      function of temperature, potential and time using in situ FTIR spectroscopy, and
      the results interpreted in terms of the surface chemistry of the Ru(000 1)
      electrode and compared to those obtained during our previous studies on the
      adsorption of CO under the same conditions. It was found that no dissociative
      adsorption or electro-oxidation of methanol takes place at Ru(0001) at potentials
      < 900 mV vs. Ag/AgCl, and at all three temperatures employed, 10, 25 and 50
      degrees C. However, both formaldehyde and formic acid did undergo dissociative
      adsorption, even at -200 mV, to form linear (CO(L)) and 3-fold-hollow (COH)
      binding CO adsorbates. In contrast to the adsorption of CO, it was found that
      increasing the temperature to 50 degrees C markedly increased the amount of CO
      adsorbates formed on the Ru(0001) surface from the adsorption of both
      formaldehyde and formic acid. On increasing the potential, the electro-oxidation
      of the CO adsorbates to CO2 took place via reaction with the active (1 x 1)-O
      oxide. Formic acid was detected as a partial oxidation product during
      formaldehyde electro-oxidation. At all three temperatures employed, it was found
      that adsorbed CO species were formed from the adsorption of both formic acid and
      formaldehyde, and were oxidised to CO2 faster than was observed in the
      experiments involving CO adsorbed from CO(g), suggesting a higher mobility of the
      CO adsorbates formed from the adsorption of the HCOOH and HCHO. At potentials >
      1000 mV, both the oxidation of formic acid to CO2 and the oxidation of
      formaldehyde to both CO2 and formic acid were significantly increased, and the
      oxidation of methanol to CO2 and methyl formate was observed, all of which were
      attributed to the formation of an active RuO2 phase on the Ru(0001) surface.

PMID- 12227574
TI  - Potential dependence of step and kink energies on Au(100) electrodes in sulfuric
      acid.
AB  - Using electrochemical STM we studied monolayer high Au islands on Au(100)
      electrodes in sulfuric acid as a function of the electrode potential. We made use
      of theoretical and experimental methods recently developed for UHV experiments on
      metal islands. It is demonstrated that these models are likewise applicable to
      islands on metal electrodes in a liquid environment. From a quantitative analysis
      of the equilibrium island shape and of the island shape fluctuations we
      determined the step free energy (line tension) as a function of orientation and
      the kink energy, and the dependence of these quantities on the electrode
      potential. In a first approach to a theoretical understanding the electrostatic
      contributions to the line tension are considered. It is concluded that these
      contributions should add significantly to the observed variation with the
      potential. This fails however to provide essential features of the experimental
      result.

PMID- 12227575
TI  - What can we learn about electrode-chemisorbate bonding energetics from
      vibrational spectroscopy? An assessment from density functional theory.
AB  - An analysis is presented of the manner and extent to which the metal surface
      chemisorbate bond energetics and geometries as functions of the metal and the
      applied field can be correlated with vibrational frequencies, with specific
      reference to electrochemical systems. Emphasis is placed on metal-adsorbate
      stretching frequencies, vM-A, using oxygen and carbon monoxide chemisorption as
      illustrative examples; the intramolecular stretch (vCO) of the latter adsorbate
      is also examined in view of the extensive experimental utilization of this
      vibrational mode. Results based on Density Functional Theory (DFT) are presented
      for finite-cluster models of Pt-group and coinage-metal (111) surfaces. The DFT
      calculations enable a separation between steric repulsion and orbital
      contributions to the potential-energy surface (PES), and additionally, in the
      case of CO chemisorption, between the 5sigma and 27pi* orbital components. While
      rough metal-dependent correlations between vM-A and the surface binding energy, 
      Eb, are observed, such a relationship is not expected in general. Thus for CO
      chemisorption, the variations in -Eb are affected more by changes in the 5sigma
      rather than 2pi* orbital energies, whereas these components influence the M-CO
      stretching frequency, vM-CO, to a comparable extent. Moreover, the metal
      dependent vCO frequencies do not correlate even qualitatively with -Eb; this is
      because the former are dominated by 2pi*, rather than 5sigma, interactions. The
      factors influencing the field (F) (and hence electrode potential) dependence of
      Eb versus VM-CO and vCO mirror somewhat this pattern. While the field-dependent
      influence of the 5sigma and 2pi* interactions are offsetting, the latter affects
      the vM CO-F, and especially the vCO-F, behavior to a greater extent than the -Eb
      F dependence. Generally, then, the lack of broad-based correlations between
      chemisorbate vibrational frequencies and binding energetics can be understood in
      terms of the differing influence of the individual interaction components on the
      PES well shape and depth. The description of such bonding contributions in terms
      of dipole-moment parameters is illustrated. Also considered are relations between
      vibrational frequencies and bond lengths.

PMID- 12227576
TI  - Dynamics of CO at the solid/liquid interface studied by modeling and simulation
      of CO electro-oxidation on Pt and PtRu electrodes.
AB  - We consider theoretical models for CO monolayer oxidation on stepped Pt single
      crystal electrodes and Ru-modified Pt(111) electrodes. For both systems, our aim
      is to assess the importance of CO surface diffusion in reproducing the
      experimental chronoamperometry or voltammetry. By comparing the simulations with
      the experimental chronoamperometric transients for CO oxidation on a series of
      stepped Pt surfaces, it was concluded that mixing of CO on the Pt(111) terrace is
      good, implying rapid diffusion (N. P. Lebedeva, M. T. M. Koper, J. M. Feliu and
      R. A. van Santen, J. Phys. Chem. B, submitted). We discuss here a more detailed
      model in which the CO adsorbed on steps is converted into CO adsorbed on terraces
      as the oxygen-containing species occupy the steps (as observed experimentally on
      stepped Pt in UHV), followed by a subsequent oxidation of the latter, to
      reproduce the observed chronoamperometry on stepped surfaces with a higher step
      density. On Ru-modified Pt(111), the experimentally observed splitting of the CO
      stripping voltammetry into two stripping peaks, may suggest a slow diffusion of
      CO on Pt(111). This apparent contradiction with the conclusions of the
      experiments on stepped surfaces, is resolved by assuming a weaker CO binding to a
      Pt atom which has Ru neighbors than to "bulk" Pt(111), in agreement with recent
      quantum-chemical calculations. This makes the effective diffusion from the
      uncovered Pt(111) surface to the perimeter of the Ru islands, which are
      considered to be the active sites in CO oxidation electrocatalysis on PtRu
      surfaces, very slow. Different models for the reaction are considered, and
      discussed in terms of their ability to explain experimental observations.

PMID- 12227577
TI  - The electrochemical oxidation of carbon monoxide adsorbed on Pt(111) in aqueous
      electrolytes as monitored by in situ potential step-second harmonic generation.
AB  - The dynamics of electrooxidation of adsorbed CO on Pt(111) microfacets was
      examined in CO-saturated 0.1 M HClO4 aqueous solutions by in situ time resolved
      second harmonic generation (SHG). Analysis of the temporal dependence of the
      intensity of the SHG signals recorded for experiments in which the potential was
      stepped to values high enough for adsorbed CO oxidation to ensue, was found to be
      consistent with the mean field theory model, yielding rate constants somewhat
      higher than those reported by Lebedeva et al. (N. P. Lebedeva, M. T. M. Koper, J.
      M. Feliu and R. A. v. Santen, J. Electroanal. Chem., 2002, 524-525, 242-251) in
      sulfuric acid solutions. The smaller rates observed by these authors may be
      ascribed to the presence of anions, ie. in all likelihood bisulfate, which are
      capable of competing effectively for Pt sites thereby blocking formation of
      oxygenated species on the surface. Also discussed in this work are the virtues
      and limitations of in situ SHG for monitoring fast surface processes.

PMID- 12227578
TI  - Diffusion on a nanoparticle surface as revealed by electrochemical NMR.
AB  - Surface diffusion of chemisorbed CO (from MeOH electrochemisorption) on pure and
      Ru-modified nanoscale Pt electrocatalyst surfaces has been investigated by solid
      state electrochemical NMR (EC-NMR) in the presence of supporting electrolyte.
      Temperature-dependent nuclear spin-spin and spin-lattice relaxation measurements
      enable the diffusion activation energy, E, to be deduced. It is shown that the
      activation energy E correlates with the steady state current for MeOH electro
      oxidation. A simple two-dimensional collision theory model is proposed to explain
      this intriguing observation, which may provide new mechanistic insights into the
      promotion of CO-tolerance in Pt/Ru fuel cell catalysts.

PMID- 12227579
TI  - Novel method for the investigation of single nanoparticle reactivity.
AB  - The reactivity of planar surfaces has been well investigated but there are many
      new unexplored aspects involved in the reactivity of nanoparticle surfaces. Most
      investigative methods only measure the average properties of the particles
      present on the surface. In order to investigate the local reactivity of
      nanoparticles, the STM tip electrode can be used as a local sensor. The
      feasibility of this approach is demonstrated by detecting some of the hydrogen
      (through the hydrogen oxidation reaction current at the tip) which is evolved at
      a single Pd particle on the Au(111) substrate at a constant distance from the
      tip. In principle, it is thereby possible to determine the reactivities of
      surfaces on a nanometre scale. To avoid interference from different reactive
      particles it is essential to use electrodes with a very low particle density.
      Hence, in this investigation electrodes with single Pd particles which were
      deposited from the STM tip onto the substrate are used. Results of potential
      dependent measurements at single metal nanoparticles will be shown and the
      possibilities and limitations of the approach will also be discussed.

PMID- 12227580
TI  - Electron and ion transfer through multilayers of gold nanoclusters covered by
      self-assembled monolayers of alkylthiols with various functional groups.
AB  - The electrochemical characteristics of various kinds of multilayers of gold
      nanoclusters (GNCs) were investigated. Two types of gold nanoclusters, one
      covered by self-assembled monolayers (SAMs) of mercaptoundecanoic acid (MUA),
      hexanethiol (C6SH), and ferrocenylhexanethiol (FcC6SH), MHF-GNC, and the other
      with MUA and C6SH, MH-GNC, were used. The multilayers were constructed on a
      Au(111) surface based on a carboxylate/metal cation (Cu++)/carboxylate or
      carboxylate/cationic polymer (poly(allylamine hydrochloride):PAH)/carboxylate
      electrostatic interaction. While the multilayers constructed by the former method
      were stable only in nonaqueous solutions, those constructed by the latter method
      were stable even in aqueous solutions. Electrochemical measurements of the
      multilayers of MHF-GNCs showed a pair of waves corresponding to the redox of the
      ferrocene group around 350-480 mV and the charge of these peaks, i.e., the amount
      of adsorbed GNC, increased linearly with the construction cycle up to 6 cycles in
      the former and to 18 cycles in the latter. A rather reversible redox response of
      the ferrocene moiety was observed even at the gold electrodes with five GNC
      layers of two different sequences in which MHF-GNC exists as the layer closest to
      the gold electrode, ie., the first layer, or as the outermost layer with MH-GNC
      in the other layers. These results show the facile transfer of electrons and ions
      through the multilayers of the SAM-covered GNCs and electron transfer between the
      ferrocene moiety and the Au(111) electrode takes place through the GNC cores by
      hopping.

PMID- 12227581
TI  - Ground vs. excited state electron transfer: adsorbed monolayers and trimers in
      solution.
AB  - Transient emission spectroscopy has been used to probe the rate of photoinduced
      electron transfer between metal centres within a novel trimeric complex
      [[Os(bpy)2(bpe)2][Os(bpy)2Cl]2]4+, where bpy is 2,2'-bipyridyl and bpe is trans
      1,2-bis-(4-pyridyl)ethylene. Transient emission experiments on the trimer, and on
      [Os(bpy)2 (bpe)2]2+ in which the [Os(bpy)2 Cl]+ quenching moieties are absent,
      reveal that the rate of photoinduced electron transfer (PET) across the bpe
      bridge is 1.3 +/- 0.1 x 10(8) s(-1). Investigations into the driving forces for
      oxidation and reduction of the electronically excited state within the trimer
      indicate that quenching of the [Os(bpy)2 (bpe)2]2+ centre within the trimer
      involves electron transfer from the [bpe Os(bpy)2 Cl]+ centres to the
      electronically excited state with a driving force of -0.3 eV. Monolayers of the
      complex, [Os(bpy)2 bpe pyridine]2+, have been formed by spontaneous adsorption
      onto platinum microelectrodes and used to probe the dynamics of electron transfer
      across the trans-1,2-bis-(4-pyridyl)ethylene bridge in the ground state. These
      monolayers are stable and exhibit well defined voltammetric responses for the
      Os2+/3+ redox reaction. Cyclic voltammograms recorded at high scan rates can be
      accurately modelled according to a non-adiabatic electron transfer model based on
      the Marcus theory using a standard heterogeneous electron transfer rate constant,
      k(o), of 3.1 +/- 0.2 x 10(4) s(-1) and a reorganization energy of 0.4 +/- 0.1 eV.
      This rate constant is a factor of approximately two orders of magnitude smaller
      than that found for photoinduced electron transfer across the same bpe bridge for
      identical driving forces. This significant difference is interpreted in terms of
      both the nature of the orbitals involved in electrochemically and optically
      driven electron transfer, as well as the strength of electronic coupling between
      two molecular components as opposed to a molecular component and a metal
      electrode.

PMID- 12227582
TI  - Electrochemical and PM-IRRAS studies of potential controlled transformations of
      phospholipid layers on Au(111) electrodes.
AB  - Chronocoulometry and photon polarisation modulation infrared reflection
      absorption spectroscopy (PM-IRRAS) have been employed to study the fusion of
      dimyristoylphosphatidylcholine (DMPC) vesicles onto a Au(111) electrode surface.
      The results show that fusion of the vesicles is controlled by the electrode
      potential or charge at the electrode surface (sigmaM). At charge densities of -15
      microC cm(-2) < sigmaM < 0 microC cm(-2), DMPC vesicles fuse to form a condensed
      film. When sigmaM < -15 microC cm(-2), de-wetting of the film from the electrode
      surface occurs. The film is detached from the electrode surface; however,
      phospholipid molecules remain in its close proximity in an ad-vesicle state. The
      state of the film can be conveniently changed by adjustment of the potential
      applied to the gold electrode. PM-IRRAS experiments demonstrated that the
      potential-controlled transitions between various DMPC states proceed without
      conformational changes and changes in the packing of the acyl chains of DMPC
      molecules. However, a remarkable change in the tilt angle of the acyl chains with
      respect to the surface normal occurs when ad-vesicles spread to form a film at
      the gold surface. When the bilayer is formed at the gold surface, the acyl chains
      of DMPC molecules are significantly tilted. The IR spectra have also demonstrated
      a pronounced change in the hydration of the polar head region that accompanies
      the spreading of ad-vesicles into the film. For the film deposited at the
      electrode surface, the infrared results showed that the temperature-controlled
      phase transition from the gel state to the liquid crystalline state occurs within
      the same temperature range as that observed for aqueous solutions of vesicles.
      The results presented in this work show that PM-FTIR spectroscopy, in combination
      with electrochemical techniques, is an extremely powerful tool for the study of
      the structure of model membrane systems at electrode surfaces.

PMID- 12227583
TI  - Dynamics of regioregular conducting polymer electrodes in response to
      electrochemical stimuli.
AB  - We report thickness shear mode resonator acoustic wave data for films of
      regioregular poly(3-hexylthiophene) films exposed to acetonitrile solutions of
      LiClO4. Both the current- and acoustic wave-responses to constant (or slowly
      swept) potential show different regimes, whose characteristics, which are quite
      different to those of regiorandom electropolymerized films, can be interpreted in
      terms of crystalline and non-crystalline material. Oxidation of crystalline
      material, which occurs at low potentials, is dominated by anion transfer; as a
      result of the associated electrostatic effects, the film stiffens. Oxidation of
      non-crystalline material, which occurs at more positive potentials, involves
      significant solvent transfer; the solvent softens the film. We have been able to
      determine film thickness changes and shear modulus components (based on a
      homogeneous film model) (i) as functions of potential (ie. charge state) and of
      temperature at fixed potential, and (ii) as a function of time following a
      potential step. In each case, we have been able to rationalise the
      electrochemical and viscoelastic phenomena in terms of electrochemically
      controlled film composition, of which the most significant component is solvation
      state.

PMID- 12227584
TI  - In situ video-STM studies of dynamic processes at electrochemical interfaces.
AB  - Atomic-scale dynamic processes during Cu(100) dissolution/deposition in pure and
      Cu-containing 0.01 M HCl solution were studied in situ by high-speed
      electrochemical STM (video-STM). Direct observations of the equilibrium
      fluctuations at atomic kinks in the steps on the crystal surface due to the local
      removal/addition of atoms reveal the same anisotropic behavior found previously
      in Cu-free electrolytes, caused by the influence of the ordered (2 x 2) Cl
      adlayer on the kink structure. A first quantitative analysis of these
      fluctuations and interpretation in terms of a local current exchange density was
      attempted. In addition, observations on the nucleation of vacancy- or ad-rows at
      terrace corners and within the Cu steps are presented and the relevance of these
      processes for the macroscopic current density is discussed.

PMID- 12227585
TI  - Concluding remarks: towards fourth generation electrochemistry.

PMID- 12227586
TI  - Halide adsorption on single-crystal silver substrates: dynamic simulations and ab
      initio density functional theory.
AB  - We investigate the static and dynamic behaviors of a Br adlayer electrochemically
      deposited onto single-crystal Ag(100) using an off-lattice model of the adlayer.
      Unlike previous studies using a lattice-gas model, the off-lattice model allows
      adparticles to be located at any position within a two-dimensional approximation
      to the substrate. Interactions with the substrate are approximated by a
      corrugation potential. Using density functional theory (DFT) to calculate surface
      binding energies, a sinusoidal approximation to the corrugation potential is
      constructed. A variety of techniques, including Monte Carlo and Langevin
      simulations, are used to study the behavior of the adlayer. The lateral root-mean
      square (rms) deviation of the adparticles from the binding sites is presented
      along with equilibrium coverage isotherms, and the thermally activated Arrhenius
      barrier-hopping model used in previous dynamic Monte Carlo simulations is tested.

PMID- 12227587
TI  - Hydration processes of electrolyte anions and cations on pt(111), Ir(111),
      Ru(001) and Au(111) surfaces: coadsorption of water molecules with electrolyte
      ions.
AB  - Water adsorption on Pt( 111) and Ru(001) treated with oxygen, hydrogen chloride
      and sodium atom at 20 K has been studied by Fourier transform infrared
      spectroscopy, scanning tunneling microscopy and surface X-ray diffraction. Water
      molecules chemisorb predominantly on the sites of the electronegative additives,
      forming hydrogen bonds. Three types of hydration water molecules coordinate to an
      adsorbed Na atom through an oxygen lone pair. In contrast, water molecules adsorb
      on electrode surfaces in a simple way in solution. In 1 mM CuSO4 + 0.5 M H2SO4
      solution on an Au(111) electrode surface, water molecules coadsorb not only with
      sulfuric acid anions through hydrogen bonding but also with copper, over wide
      potential ranges. In the first stage of underpotential deposition (UPD), each
      anion is accommodated by six copper hexagon (honeycomb) atoms on which water
      molecules dominate. At any UPD stage water molecules interact with both the
      copper atom and sulfuric acid anions on the Au(111) surface. Water molecules also
      coadsorb with CO molecules on the surface of 2 x 2-2CO-Ru(001). All of the
      hydration water molecules chemisorb weakly on the surfaces. There appears to be a
      correlation between the orientation of hydrogen bonding water molecules and the
      electrode potential.

PMID- 12227588
TI  - Self consistent direct dynamics studies of interfaces.
AB  - To reach the goal of prediction of electrochemical behavior from first
      principles, it appears increasingly evident that an intermediate stage, between
      ab initio calculation and Monte Carlo or classical molecular dynamics, will be
      required. Here we report progress on the development of such an intermediate
      computational method, using a self consistent tight binding approach, and report
      some preliminary results on the structure and dynamics of water on the 110 face
      of rutile titanium dioxide.

PMID- 12227589
TI  - Being good at doing good? Quality and accountability of humanitarian NGOs.
AB  - Quality enhancement of humanitarian assistance is far from a technical task. It
      is interwoven with debates on politics of principles and people are intensely
      committed to the various outcomes these debates might have. It is a field of
      strongly competing truths, each with their own rationale and appeal. The last few
      years have seen a rapid increase in discussions, policy paper and organisational
      initiatives regarding the quality of humanitarian assistance. This paper takes
      stock of the present initiatives and of the questions raised with regard to the
      quality of humanitarian assistance.

PMID- 12227590
TI  - Destocking as a drought-mitigation strategy: clarifying rationales and answering
      critiques.
AB  - The idea of externally assisted emergency destocking of pastoralists has gained
      currency in recent years: increasing the incentives for pastoralists to sell
      animals, or removing the constraints to selling animals in the early stages of
      drought. We identify two separate rationales put forward by proponents of
      destocking: environmental benefits and purchasing power/welfare benefits. We
      consider whether specific recent critiques of 'new range ecology' and
      specifically of 'tracking policies' do in fact provide arguments against
      emergency destocking in pastoralist areas. We illustrate some of these themes
      with a case study of a successful destocking exercise in northern Kenya where a
      very specific form of support was requested and received by pastoralists
      themselves. The sorts of destocking that work are likely to have significant
      effects on pastoralist purchasing power at key points of the drought cycle, but
      minimal effects on the environment. Clarifying these points will make it easier
      to promote destocking as a drought-mitigation policy.

PMID- 12227591
TI  - Nutritional response to the 1998 Bangladesh flood disaster: Sphere minimum
      standards in disaster response.
AB  - In this study we use a cross-sectional survey to evaluate the nutritional
      response to the 1998 Bangladesh Flood Disaster by 15 relief agencies using
      standards developed by the Sphere Project. The Sphere Project is a recent attempt
      by agencies around the world to establish universal minimum standards for the
      purpose of ensuring quality and accountability in disaster response. The main
      outcomes measured were resources allocated to disaster relief types of relief
      activities and percentage of agencies meeting selected Sphere food aid and
      nutrition indicators. Although the process of nutritional response was measured,
      specific nutritional and health outcomes were not assessed. This review found
      that self-reported disaster and nutritional resources varied widely between
      implementing agencies, ranging from US $58,947 to $15,908,712. The percentage of
      resources these agencies allocated to food aid and nutritional response also
      varied, ranging from approximately 6 to 99 per cent of total resources. Agencies
      met between 8 and 83 per cent of the specific Sphere indicators which were
      assessed Areas in which performance was poor included preliminary nutritional
      analysis; beneficiary participation and feedback; disaster preparedness during
      non-emergency times; monitoring of local markets and impact assessment. Agencies
      were generally successful in areas of core humanitarian response, such as
      targeting the vulnerable (83 per cent) and monitoring and evaluating the process
      of disaster response (75 per cent). The results here identify both strengths and
      gaps in the quality of humanitarian response in developing nations such as
      Bangladesh. However, they also raise the question of implementing a rights-based
      approach to disaster response in nations without a commitment to meeting positive
      human rights in non-disaster times.

PMID- 12227592
TI  - Zimbabwe's Child Supplementary Feeding Programme: a re-assessment using household
      survey data.
AB  - In 1992-3 and 1995-6, Zimbabwe used a Child Supplementary Feeding Programme
      (CSFP) to combat child malnutrition during drought-induced emergencies. Previous
      evaluations of the CSFP relied on routine administrative data and key informant
      interviews and made only cursory use of available household survey data. These
      evaluations concluded that the CSFP was effective in preventing an increase in
      malnutrition among children under five, especially in 1992-3. The more-detailed
      analysis of household surveys provided in this article suggests that CSFP
      coverage was generally patchy and disappointingly low, especially in 1995-6.
      There is little evidence that children from poor or nutritionally vulnerable
      households got preferential access to supplementary feeding. The CSFP failed to
      feed many malnourished and nutritionally vulnerable children even in areas where
      the programme was operating. Household survey evidence suggests that the CSFP's
      impact on nutritional status was likely marginal, especially in 1995-6.

PMID- 12227593
TI  - The Ethiopian crisis of 1999-2000: lessons learned, questions unanswered.
AB  - During 1999-2000, Ethiopia was brought to the edge of a major disaster, with some
      10 million people estimated to be in need offood assistance at the height of the
      crisis. A repeat of the catastrophic famine of 1984-5 was avoided, but the
      numbers of people affected, the loss of life and the destruction of livelihoods
      made this one of the most serious crises in the Horn of Africa in the past 15
      years. The humanitarian community has been slow to recognise the lessons of 1999
      2000, and there have been surprisingly few attempts to conduct a serious, post
      event evaluation of the overall crisis and response. The label famine averted'
      seems to summarise the crisis to the satisfaction of most parties involved. This
      paper reviews the crisis, the events that led up to it and the response effort.
      It examines thefactors that contributed to making this crisis so serious, in
      order to draw conclusions and note issues that are relevant to current thinking
      about disaster preparedness and response - in Ethiopia and elsewhere. Some of the
      lessons learned from the 1999-2000 crisis are not new. However, the veryfact that
      mistakes have been repeated should be a lesson to the humanitarian community.

PMID- 12227594
TI  - Detection of the most optimal measuring points for water quality variables:
      application to the river water quality model of the River Dender in ESWAT.
AB  - This paper presents a methodology for the definition of an optimal set of
      sampling data for the calibration of a river water quality model. Starting with
      an extensive set of measurements, it is the aim to reduce those data to obtain
      just as much data as necessary for a calibration with an acceptable uncertainty
      in the parameters. The method requires a model for the river under examination
      and the availability of samples for a first calibration of the model. With the
      model, synthetic time series are generated, which can be used as virtual
      observations. In the next step, the method of D-optimal design is applied. The
      amount, frequency, period, place and kind of variables measured of the water
      samples that gives the most reliable estimates of the parameters of the model are
      considered to be the best observations that can be made for that river. Also, the
      percentage of improvement of the reliability can be defined, as a function of the
      observations. The method is applied to the river Dender.

PMID- 12227595
TI  - Estimation of pharmaceutical residues in primary and secondary sewage sludge
      based on quantities of use and fugacity modelling.
AB  - A general procedure was developed for estimating the concentrations of
      pharmaceutical residues in fresh primary and secondary sewage sludge. Prescribed
      quantities coupled with information on the various excretion ratios of 20
      pharmaceuticals and 2 of their metabolites enabled prediction of the overall
      rates of excretion into Australian sewage. Fugacity modelling was applied to
      predict concentrations of these residues in fresh primary and secondary sludge.
      Predicted concentrations ranged from 10(-3)-884 microg/L in primary sludge and
      10(-4)-36 microg/L in secondary sludge. Overall rates of removal to sludges
      ranged from 1-39%. The accuracy of the model was verified by comparison to
      analytical data.

PMID- 12227596
TI  - Surface and subsurface irrigation with effluents of different qualities and
      presence of Cryptosporidium oocysts in soil and on crops.
AB  - A large variety of human pathogens are excreted in wastewater including bacteria,
      viruses, protozoan cysts and helminth eggs. In raw sewage, human pathogens reach
      high numbers, thereafter decreasing successively at each treatment step. However,
      the final effluents still contain a large fraction of these pathogens that may
      pose a serious public health. Among the various crops irrigated with effluents,
      vegetables are the most vulnerable to contamination. Vegetables, usually eaten
      raw (uncooked) or with rich dressings (causing regrowth of some pathogenic
      bacteria) pose the main threat to humans. The importance of microbiological and
      parasitological criteria for reused water has been repeatedly emphasized. Some
      microbiological recommendations based on epidemiological data have been
      established for untreated wastewater, there is still a need to define the
      criteria for effluent quality required for unrestricted crop irrigation. This
      paper presents a field study comparison of two irrigation methods: surface and
      subsurface of field crops (mainly vineyard) and follow-up of Cryptosporidium
      oocysts in soil at different depths (0 to 90 cm). Oocysts were isolated at all
      depths without a clear pattern of distribution (0 to 640 oocysts/g). In addition
      different vegetables irrigated with different effluent qualities were tested for
      the presence of Cryptosporidium oocysts and Giardia cysts. The highest prevalence
      of oocysts was found on zucchini that has a sticky and hairy outer surface (80 to
      10,000 oocysts/0.5 kg).

PMID- 12227598
TI  - Particle transport in a karst aquifer: natural and artificial tracer experiments
      with bacteria, bacteriophages and microspheres.
AB  - Fast changes in spring water quality in karst areas are a major concern for
      production of drinking water and require detailed knowledge of the complex
      interaction between karst aquifer, transport behavior of microorganisms and water
      treatment. We have conducted artificial and natural particle transport
      experiments at a karst spring with bacteria, bacteriophages, microspheres, and
      pathogens. Transport of the investigated microorganisms, turbid matter and
      chemical pullutants as well as increase in discharge are strongly related to
      precipitation and the heterogeneity of the aquifer. The indicator bacteria E.
      coli revealed a significant correlation to verotoxin-producing E coli and
      Cryptosporidium spp. We conclude that artificial particle tracers can help
      identify 'hot spots' for microbial recharge and that system parameters in spring
      water such as turbidity, UV-extinction and increase in discharge can be key
      parameters for efficient raw water management.

PMID- 12227597
TI  - Virus removal by soil passage at field scale and groundwater protection of sandy
      aquifers.
AB  - Virus removal from groundwater by soil passage often appears to be much higher
      during the first few metres due to the presence of more favorable sites for
      attachment than thereafter. A model is presented which interprets virus removal
      as a function of collision efficiencies alpha(beta) and alpha(lambda),
      inactivation rate coefficient mu(t) and rate parameter gamma. Initial high
      removal is determined by ab, which decreases exponentially at a rate g to a
      constant base removal rate that is determined by alpha(lambda) and mu(t). A
      hypothetical worst case was simulated to calculate the travel distance and time
      required for 9 log10 protection against virus contamination of groundwater wells
      in anoxic sandy aquifers. Unfavorable conditions for attachment were assumed.
      Virus was constantly leaking from a sewage pipe lying at the groundwater table.
      Mixing reduced virus concentration by 3.1 to 4.0 log10. For an additional 5.0 to
      5.9 l log10 protection against virus contamination by attachment and
      inactivation, residence times of about three to seven times longer than the
      current guideline of 60 days are needed, depending on abstraction rates, aquifer
      thickness and grain size of the sand.

PMID- 12227599
TI  - River Pollution Diagnostic System (RPDS)--computer-based analysis and
      visualisation for bio-monitoring data.
AB  - The importance of biological monitoring for the assessment of river quality is
      well established. Bio-monitoring programmes, in particular the recording of
      benthic macroinvertebrate assemblages, produce an abundance of data to support
      the process of river quality assessment. However, current data analysis
      techniques are largely based on subjective score systems that do not fully
      realise the potential information value of such complex multivariate data sets.
      More advanced techniques of data analysis and visualisation can help to maximise
      the value of biological data, and hence to more efficiently and effectively
      direct resources, funding and research. A River Pollution Diagnostic System
      (RPDS) is described. RPDS was recently developed by the authors for the
      Environment Agency in England and Wales; it aims to maximise information
      retrieval from biological and environmental data.

PMID- 12227601
TI  - Management of sensible water uses with real-time measurements.
AB  - For the protection of bankside wells and a groundwater recharge an early warning
      system had to be developed. The monitoring network design is based on sensor
      measurements only. For this purpose a new submersible spectrometer has been
      successfully tested for multi-parameter measurements directly in the medium. The
      developed system can easily be upgraded with other new sensors. Only calibration
      and validation data are supplied by conventional grab sampling and laboratory
      analysis.. A conventional testfilter improved by on-line monitoring at 5 sampling
      sites serves as a reference system. The whole system is equipped with remote
      control and the internet serves as the control centre of the network. All
      measurement data from all 9 sites are available in real time on the internet.

PMID- 12227600
TI  - Monitoring faecal contamination of the Thames estuary using a semiautomated early
      warning system.
AB  - The Colifast Early Warning System, based on measuring beta-galactosidase activity
      (2 h method), was evaluated for monitoring the level of faecal contamination in
      the upper tidal Thames. Two trials were performed, one following heavy rain in
      November 2000, the next during a dry and sunny period in July 2001. In general
      the beta-galactosidase activity and the two coliform reference methods (recovery
      following membrane filtration with membrane lauryl sulphate broth (MLSB) and
      Colilert Quantitray) were comparable. However, in several samples in July the
      beta-galactosidase activity seemed to overestimate the number of culturable
      coliforms, suggesting that the rapid enzymatic method detected beta-galactosidase
      produced by other bacterial sources, such as Aeromonas spp. or Vibrio spp., or
      nonculturable coliforms. The later could be attributed to sunlight-induced
      injury. Nevertheless, the rapid method based on beta-galactosidase activity gave
      an estimate of the level of culturable coliforms, which did not differ from both
      coliform reference methods by more than one log. Monitoring of beta-galactosidase
      activity in river water samples using the Colifast Analyser may therefore be
      useful as an early warning indicator of faecal contamination.

PMID- 12227602
TI  - Risk-based modeling of early warning systems for pollution accidents.
AB  - An early warning system is a mechanism for detecting, characterizing and
      providing notification of a source water contamination event (spill event) in
      order to mitigate the impact of contamination. Spill events are highly
      probabilistic occurrences with major spills, which can have very significant
      impacts on raw water sources of drinking water, being relatively rare. A
      systematic method for designing and operating early warning systems that
      considers the highly variable, probabilistic nature of many aspects of the system
      is described. The methodology accounts for the probability of spills, behavior of
      monitoring equipment, variable hydrology, and the probability of obtaining
      information about spills independent of a monitoring system. Spill Risk, a risk
      based model using Monte Carlo simulation techniques has been developed and its
      utility has been demonstrated as part of an AWWA Research Foundation sponsored
      project. The model has been applied to several hypothetical river situations and
      to an actual section of the Ohio River. Additionally, the model has been
      systematically applied to a wide range of conditions in order to develop general
      guidance on design of early warning systems.

PMID- 12227603
TI  - Application of recombinant fluorescent mammalian cells as a toxicity biosensor.
AB  - With respect to developing a more sensitive biosensor, a recombinant fluorescent
      Chinese Hamster Ovary cell line was used for the monitoring of various toxicants.
      Both cell lines, EFC-500 and KFC-A10, were able to detect toxicants sensitively.
      They were characterized with mitomycin C and gamma-ray as genotoxicants and
      bisphenol A, nonylphenol, ziram and methyl bromide as possible and known EDCs.
      When compared to each other, the response of KFC-A10 was generally more
      informative and sensitive. Compared to typical bacterial biosensor systems, these
      cell lines offered a sensitivity of 2- to 50-fold greater for the tested
      chemicals. Based on these results, the use of mammalian cells offers a sensitive
      biosensor system that is not only fast, cheap and reproducible but also capable
      of monitoring the endocrine-like characteristics of environmental toxicants.

PMID- 12227604
TI  - Mass spectrometric monitoring of the degradation and elimination efficiency for
      hardly eliminable and hardly biodegradable polar compounds by membrane
      bioreactors.
AB  - Wastewaters containing or spiked with polar compounds--alkylphenolethoxylates
      (APEOs) and drugs--were treated in membrane-assisted and conventional biological
      pilot plants to eliminate these pollutants. Elimination resulting in
      metabolization or ultimate degradation was pursued by substance-specific analysis
      applying atmospheric pressure chemical ionization (APCI) in combination with mass
      and tandem mass spectrometric detection (MS and MS-MS) either in the flow
      injection (FIA) or liquid chromatographic separation (LC) mode. APEOs were
      diminished by successive cleavage of polyether chain links resulting in short
      chain APEOs or alkylphenols (AP), if the biocoenosis was adapted to the
      compounds. Lipid regulating agents (LRA) were either eliminated completely
      (etofibrate), metabolized to fenofibratic acid (fenofibrate) or diminished to a
      minimal extent (bezafibrate). Compared to the membrane microfiltration process
      the conventional activated sludge process was less successful in both APEO and
      LRA elimination.

PMID- 12227605
TI  - A kinetic model of N-nitrosodimethylamine (NDMA) formation during water
      chlorination/chloramination.
AB  - Experiments were conducted to investigate the hypothesis that N
      nitrosodimethylamine (NDMA) is a potential disinfection by-product. NDMA was
      formed by the reaction of dimethylamine (DMA) with monochloramine and also with
      free chlorine in the presence of ammonia. We proposed a mechanism for NDMA
      formation which does not require the presence of nitrite as in N-nitrosation. The
      critical NDMA formation reactions consist of i) the formation of monochloramine
      by combination of free chlorine with ammonia, ii) the formation of 1,1
      dimethylhydrazine (UDMH) intermediate from the reaction of DMA with
      monochloramine followed by, iii) the oxidation of UDMH by monochloramine to NDMA,
      and iv) the reversible chlorine transfer reaction between free
      chlorine/monochloramine and DMA which is parallel with i) and ii). A kinetic
      model was developed to validate the proposed mechanism.

PMID- 12227606
TI  - Fate of pharmaceuticals during indirect potable reuse.
AB  - The scope of this study was directed to examine different wastewater treatment
      technologies (activated sludge, trickling filter, nanofiltration, reverse
      osmosis) at full-scale facilities in Arizona and California leading to indirect
      potable reuse and their capability to remove pharmaceuticals. Additionally, the
      fate of selected pharmaceuticals was studied during soil-aquifer treatment (SAT)
      at sites where secondary and tertiary treated effluents are used for subsequent
      groundwater recharge. Facilities employing longer detention times during
      treatment (nitrifying and denitrifying plants) showed significant lower effluent
      concentration for analgesic drugs as compared to trickling filter or activated
      sludge facilities applying shorter detention times. A similar trend was observed
      for the lipid regulator gemfibrozil, which was significantly removed in
      denitrified effluents, whereas a trickling filter treated effluent exhibited
      concentration of 1,235 ng/L. Antiepileptic drugs, such as carbamazepine and
      primidone, showed no dependency on the wastewater treatment applied. None of the
      investigated drugs was detected in tertiary treated effluents after
      nanofiltration or reverse osmosis. After SAT, analgesic/anti-inflammatory drugs
      were efficiently removed after retention times of less than 6 months and
      remaining concentrations were near or below the detection limit of the analytical
      method. A high potential for biodegradation was also observed for anti
      inflammatory drugs in groundwater recharge systems. The antiepileptics
      carbamazepine and primidone represented the most dominant of all investigated
      drugs in well treated domestic effluents (nitrifying/denitrifying plants).
      Removal of carbamazepine and primidone did not seem to occur during travel times
      of more than 6 years in the subsurface.

PMID- 12227607
TI  - From municipal sewage to drinking water: fate and removal of pharmaceutical
      residues in the aquatic environment in urban areas.
AB  - Recently, the occurrence and fate of pharmaceutically active compounds (PhACs) in
      the aquatic environment was recognized as one of the emerging issues in
      environmental chemistry and as a matter of public concern. Residues of PhACs have
      been found as contaminants in sewage, surface, and ground- and drinking water
      samples. Since June 2000, a new long-term monitoring program of sewage, surface,
      ground- and drinking water has been carried out in Berlin, Germany. Samples,
      collected periodically from selected sites in the Berlin area, are investigated
      for residues of PhACs and related contaminants. The purpose of this monitoring is
      to investigate these compounds over a long time period to get more reliable data
      on their occurrence and fate in the different aquatic compartments. Moreover, the
      surface water investigations allow the calculation of season-dependent
      contaminant loads in the Berlin waters. In the course of the monitoring program,
      PhACs and some other polar compounds were detected at concentrations up to the
      microg/L-level in all compartments of the Berlin water cycle. The monitoring is
      accompanied and supported by several other investigations such as laboratory
      column experiments and studies on bank filtration and drinking water treatment
      using conventional or membrane filtration techniques.

PMID- 12227608
TI  - PCB sources and degradation in sediments of Ashtabula River, Ohio, USA,
      determined from receptor models.
AB  - The PCB pollution in Ashtabula River sediments was evaluated using a factor
      analysis (FA) model with non-negative constraints, and a chemical mass balance
      (CMB) model. The FA model identified Aroclor 1248 as the major PCB source, and
      also a congener pattern significantly different from that of any Aroclor. The CMB
      model that uses linear combinations of Aroclors, failed to reproduce the sample
      congener profiles with good statistical fit. The findings from both models
      indicate that the PCBs in Ashtabula River sediments have undergone significant
      alterations changing their profiles from those of the original sources. These
      alterations may be explained by the anaerobic dechlorination of highly
      chlorinated congeners, according to dechlorination activities H/H'.

PMID- 12227609
TI  - Identification of the source of faecal pollution in contaminated rivers.
AB  - Identifying the source of faecal pollution is important to enable appropriate
      management of faecal pollution of water. Four independent assays for faecal
      source discrimination have been developed and implemented in our lab. These
      assays detect fluorescent whitening agents, faecal sterols, Bifidobacterium
      adolescentis and Rhodococcus coprophilus. The combination of these indicators is
      able to identify human derived faecal pollution in rivers containing inputs from
      septic tanks, municipal oxidation ponds, farmed animals and feral animals.

PMID- 12227610
TI  - A broad spectrum analytical scheme for the screening of endocrine disruptors
      (EDs), pharmaceuticals and personal care products in wastewaters and natural
      waters.
AB  - This paper describes the implementation of a broad-spectrum analytical scheme
      which was used at three wastewater plants for the screening of organic
      micropollutants. The more than 200 compounds identified comprised a variety of
      endocrine disrupters, pharmaceutical compounds and personal care products. Glycol
      ethers which have well established effects on the development of the embryo were
      outstanding in all plants investigated. The first plant, which was investigated
      at various stages of treatment, was quite efficient at removing undesirable
      compounds. The second plant, which received 50% of effluents from pharmaceutical
      industries, released low but significant levels of drugs. An antibiotic,
      cyclamidomycine, was identified in the effluent from the third plant.

PMID- 12227611
TI  - Disclosure.

PMID- 12227612
TI  - Familial dyslexia: neurocognitive and genetic correlation in a large Finnish
      family.
AB  - Neuropsychological findings of individuals with dyslexia (n=24) from a large,
      three-generation Finnish family are presented. We have previously performed whole
      genome linkage scanning in this family and found that dyslexia in this kindred
      segregates with a single locus in the pericentromeric area of chromosome 3. Those
      included in the analyses were carefully evaluated for general cognitive ability,
      reading and spelling skills, and reading-related neurocognitive skills. The
      neurocognitive type of dyslexia segregating in this family consisted of deficits
      in phonological awareness, verbal short-term memory, and rapid naming. Severe
      dyslexia also seemed to be connected with a general language difficulty and was
      most common in the eldest generation.

PMID- 12227613
TI  - Cervical accelerometry in preterm infants.
AB  - The objective of this study was to develop a method to use digital signal
      processing (DSP) technology to describe quantitatively and statistically swallow
      associated sounds in preterm infants and to use this method to analyze changes as
      infants mature. Twelve recordings of accelerometric and physiological data on
      bottle-feeding preterm infants between 32 and 39 weeks' postmenstrual age (PMA)
      were analyzed. Cervical auscultation was performed using an accelerometer
      attached over the larynx. Acoustic data were recorded and graphically displayed
      using DSP software. Initial discrete sounds (IDSs) were identified and used to
      construct an average waveform from which a 'variance index' (VI) was calculated
      for each infant. The shape of the IDS waveforms became progressively more uniform
      with advancing PMA, as indicated by a significant inverse correlation between VI
      and PMA (r=0.739; p=0.006). DSP technology facilitated the development of a new
      method to quantitatively analyze feeding in preterm infants. This method provides
      an elegant tool to track maturation of infant feeding and assessing feeding
      readiness. This technique makes the interpretation of cervical auscultation data
      less subjective by replacing the verbal description of the sounds of feeding with
      quantitative numeric values. It is anticipated that this method can be automated
      to facilitate further the analysis of cervical accelerometry data.

PMID- 12227614
TI  - Qualitative analysis of therapeutic motor intervention programmes for children
      with cerebral palsy: an update.
AB  - This study presents a comprehensive evaluation of therapeutic motor interventions
      for children with or at risk for cerebral palsy (CP), examining 50 studies
      covering the period from 1990 to 2001. The purpose was to review noticeable
      changes in the scientific quality of the studies and to highlight trends and
      changes in the nature of the evaluated programmes. Our results were compared with
      those of Vermeer and Bakx (1990) who reviewed the period from 1980 to 1989. It
      was concluded that fundamental research with adequate methodology was applied
      more often in the study period than in the period reviewed by Vermeer and Bakx.
      However, these developments did not lead to a substantial improvement in the
      scientific foundation of the interventions under study. Single case studies,
      combined with efforts to develop measures specifically for children with CP and
      with high sensitivity, might make more valuable contributions to the scientific
      justification of therapeutic interventions.

PMID- 12227615
TI  - Comparing tests of tactile sensibility: aspects relevant to testing children with
      spastic hemiplegia.
AB  - Children with hemiplegic cerebral palsy (OP) commonly exhibit tactile sensory
      deficiencies in their hands in addition to their motor problems. The aim of this
      study was to compare and evaluate the usefulness of some common tests of tactile
      sensibility for use with children with hemiplegic CP. Twenty-five children with
      hemiplegia aged between 5 and 18 years, and 19 control individuals participated.
      All children were examined with Semmes-Weinstein monofilaments, two-point
      discrimination (2PD), stereognosis of familiar objects, stereognosis of forms,
      and functional sensibility. Dexterity, spasticity, and bimanual task performance
      were also assessed. Results from the different sensory tests deviated greatly. We
      found three tests to be useful: 2PD of 3 mm spacing, which was the most sensitive
      test, stereognosis of familiar objects, and functional sensibility assessed
      through the Pick-up test (comparing performance with and without the influence of
      vision). Stereognosis of forms and threshold values of touch (Semmes-Weinstein
      monofilaments) are seemingly less useful tests for children with CNS impairments.
      Deficient sensibility was strongly related to dexterity. Aspects concerning the
      testing methodology are discussed.

PMID- 12227616
TI  - Developmental outcome, including setback, in young children with severe visual
      impairment.
AB  - This study retrospectively investigated the developmental perspective of 69
      children (40 males, 29 females) with 'potentially simple' congenital disorders of
      the peripheral visual system: development was examined in the context of degree
      of visual impairment. Developmental and visual assessments were carried out at 10
      to 16 months (Time 1) and 27 to 54 months of age (Time 2). Participants were
      grouped according to (1) visual status: profound visual impairment (PVI), severe
      visual impairment (SVI); (2) developmental status on the Reynell-Zinkin scales. A
      majority of the sample showed normal development on all subscales (62% Time 1,
      57% Time 2). Those with PVI were more developmentally vulnerable than SVI with a
      greater incidence of (1) uneven developmental profile at Time 1 (48% PVI, 16%
      SVI); (2) global learning difficulties at Time 2 (37% PVI, 0% SVI); (3) delay on
      individual subscales at Time 2 (p<0.02 PVI versus SVI); (4) deceleration (verbal
      comprehension 74% PVI, 24% SVI, sensorimotor understanding 70% PVI, 27% SVI); and
      (5) severe developmental setback (33% PVI, 7% SVI). Risk factors of visual level,
      age, and sex for poor developmental outcome in infants with visual impairment
      were established.

PMID- 12227617
TI  - Physical capacity in non-ambulatory people with Duchenne muscular dystrophy or
      spinal muscular atrophy: a longitudinal study.
AB  - The purpose of this study was to describe functional ability, muscle strength,
      forced vital capacity, and clinical events in participants with Duchenne muscular
      dystrophy (DMD) or spinal muscular atrophy (SMA) in the non-ambulatory stages of
      the diseases. Nineteen non-ambulatory participants with DMD (all males; 13 to 24
      years) and 13 with SMA (six males, seven females; 11 to 57 years) were assessed
      once a year over 5 years. The assessments comprised functional ability measured
      with the EK scale and upper extremity grade, muscle strength measured with the
      manual muscle test, and forced vital capacity defined as a percentage of normal
      values (FVC%). In the DMD group all variables measured deteriorated and there was
      a direct correlation between them. In the SMA group only muscle strength and FVC%
      deteriorated and there was no close relation between the variables measured. In
      the DMD group, 16 participants had cardiorespiratory clinical events leading to
      death in five cases. In the SMA group only four participants had respiratory
      clinical events, none leading to death. Although the participants with SMA had
      been extremely weak and non-ambulatory since early childhood they were older and
      less exposed to life-threatening events than the participants with DMD.

PMID- 12227618
TI  - Prevalence and characteristics of children with cerebral palsy in Europe.
AB  - Following agreement on definitions and classification, a central database was set
      up to include information on over 6000 children with cerebral palsy (CP) from 13
      geographically defined populations in Europe. The overall rate for the period
      1980 to 1990 was 2.08/1000 live births (95% CI 2.02 to 2.14). One in five
      children with CP (20.2%) was found to have a severe intellectual deficit and was
      unable to walk. Among babies born weighing less than 1500 g, the rate of CP was
      more than 70 times higher compared with those weighing 2500 g or more at birth.
      The rate of CP rose during the 1970s, but remained constant during the late
      1980s. Future analyses will include data from children born in the 1990s. This
      collaborative work provides a powerful means of monitoring trends in birthweight
      specific rates of CP and an infrastructure for research and service planning.

PMID- 12227619
TI  - Intracranial hypertension in neuroborreliosis.
AB  - Neuroborreliosis is an infection of the nervous system caused by the spirochete
      Borrelia burgdorferi, from which patients most commonly develop lymphocytic
      meningitis, radiculoneuritis, or cranial neuropathy. In this report a 9-year-old
      male with an unusual neurological complication of neuroborreliosis--benign
      intracranial hypertension (BIH)--is described. Clinical symptoms of BIH, which
      consist of increased CSF pressure in the absence of an intracranial mass or
      obstruction to the circulation of CSF, resolved completely after antibiotic
      therapy with ceftriaxone.

PMID- 12227620
TI  - Head growth and cranial assessment at neurological examination in infancy.

PMID- 12227621
TI  - Hip stress reduction after Chiari osteotomy.
AB  - A mathematical model was developed to study the effect of the Chiari osteotomy on
      the distribution of contact hip stress over the weight-bearing area. It was shown
      that Chiari osteotomy can increase the weight-bearing area directly (on the
      lateral side), owing to the additional area formed by the ala ossis ilii segment,
      and indirectly (on the medial side), owing to the shift of the stress pole in the
      medial direction. As a consequence, the contact hip stress is reduced after
      Chiari osteotomy. The indirect effect is important and often larger than the
      direct one. Using the proposed mathematical model and standard anteroposterior
      roentgenographs from archives, the average peak stress on the weight-bearing
      area, normalised with respect to the body weight (pmax/ W(B)), was determined
      before and after Chiari osteotomy (8,310m(-2) and 4,480 m(-2), respectively) on a
      population of 29 dysplastic hips. The difference was statistically significant (p
      < 0.005). Based on the results presented, it can be concluded that the hip joint
      contact stress in dysplastic hips considerably decreases after Chiari osteotomy,
      indicating a favourable biomechanical effect of this operation.

PMID- 12227622
TI  - Instrumented rod rotator system for spinal surgery.
AB  - An electronically instrumented rod rotator has been developed to monitor forces
      and moments applied by surgeons during the derotation manoeuver to correct spinal
      curvature. This instrumented rod rotator consisted of an inclinometer and two
      pairs of strain gauges, with all the support circuitry. The strain gauge and the
      inclinometer data were sampled with a data-acquisition system, and the results
      were displayed in real time. The device was calibrated in the laboratory and used
      on seven subjects. The precision of the load measurement of this device was +/- 5
      N in the range of 5-65N. The distance between the middle of the rod rotator
      handle to the rod position was 0.21 m. The maximum loads applied by the surgeon
      during seven surgeries were from 22 to 57N, with a torque (force x distance) from
      4.6 to 12 Nm.

PMID- 12227623
TI  - Impedance spectroscopy: an accurate method of differentiating between viable and
      ischaemic or infarcted muscle tissue.
AB  - The object of the paper is to present results that show that impedance
      spectroscopy is an accurate method of assessing the condition of muscle tissue.
      Specimens of muscle tissue were excised from 36 Atlantic salmon and subjected to
      impedance spectroscopy measurements made at intervals during an 8h period of
      ischaemia and necrosis. These measurements were conducted for three different
      temperatures and for both the longitudinal and the transverse orientations of the
      muscle fibres. The specimens were also subjected to ATP, pH and visco-elastic
      measurement and analysis to establish the degree of correlation between changes
      in these quantities and impedance spectroscopy parameters due to ischaemia. It
      was concluded that the mean relaxation time, tau(c) was the impedance
      spectroscopy parameter that best described the changes taking place in the muscle
      tissue during the post-mortem period, decreasing by 60-76% during the 8h. This
      was the case for all three temperatures and for both orientations. Furthermore,
      the muscle tissue changes due to ischaemia, as reflected in the decrease in the
      mean relaxation time tau(c), were highly correlated with changes in the tissue
      ATP, pH and dynamic shear storage modulus G'.

PMID- 12227624
TI  - Neonatal lungs--can absolute lung resistivity be determined non-invasively?
AB  - The electrical resistivity of lung tissue can be related to the structure and
      composition of the tissue and also to the air content. Conditions such as
      pulmonary oedema and emphysema have been shown to change lung resistivity.
      However, direct access to the lungs to enable resistivity to be measured is very
      difficult. We have developed a new method of using electrical impedance
      tomographic (EIT) measurements on a group of 142 normal neonates to determine the
      absolute resistivity of lung tissue. The methodology involves comparing the
      measured EIT data with that from a finite difference model of the thorax in which
      lung tissue resistivity can be changed. A mean value of 5.7 +/- 1.7 omega(m) was
      found over the frequency range 4 kHz to 813 kHz. This value is lower than that
      usually given for adult lung tissue but consistent with the literature on the
      composition of the neonatal lung and with structural modelling.

PMID- 12227625
TI  - Modelling the response of scalp sensory receptors to transcranial electrical
      stimulation.
AB  - Transcranial electrical stimulation of the brain causes considerable discomfort
      to the patient. The purpose of the study was to find out whether this could be
      affected by the choice of stimulation parameters. A spherical volume conductor
      model of the head and active compartmental models of a pyramidal motor nerve and
      scalp nociceptor were used in combination to simulate the scalp nociception to
      transcranial electrical stimulation. Scalp nociceptors were excited at distances
      of several centimetres from the electrodes. The size of the excited scalp area
      correlated with the length of the stimulation pulse. The area was 12.3, 20.4 and
      26.0 cm2, for a 10 micros, 100 micros and 1 ms constant current pulse,
      respectively. With a 100 micros constant current pulse, the threshold for motor
      excitation was 205mA and, for nociception, it was 51 mA. There was no significant
      difference between constant current and capacitor discharge pulses or between
      electrodes of different sizes. The results imply that the use of very short
      stimulation pulses can reduce the pain. If a topical anaesthesia is used to
      reduce the pain, it has to be applied on a large area around the electrodes.

PMID- 12227626
TI  - Systematic comparison of different algorithms for apnoea detection based on
      electrocardiogram recordings.
AB  - Sleep apnoea is a common disorder that is usually diagnosed through expensive
      studies conducted in sleep laboratories. Sleep apnoea is accompanied by a
      characteristic cyclic variation in heart rate or other changes in the waveform of
      the electrocardiogram (ECG). If sleep apnoea could be diagnosed using only the
      ECG, it could be possible to diagnose sleep apnoea automatically and
      inexpensively from ECG recordings acquired in the patient's home. This study had
      two parts. The first was to assess the ability of an overnight ECG recording to
      distinguish between patients with and without apnoea. The second was to assess
      whether the ECG could detect apnoea during each minute of the recording. An
      expert, who used additional physiological signals, assessed each of the
      recordings for apnoea. Research groups were invited to access data via the world
      wide web and submit algorithm results to an international challenge linked to a
      conference. A training set of 35 recordings was made available for algorithm
      development, and results from a test set of 35 different recordings were made
      available for independent scoring. Thirteen algorithms were compared. The best
      algorithms made use of frequency-domain features to estimate changes in heart
      rate and the effect of respiration on the ECG waveform. Four of these algorithms
      achieved perfect scores of 100% in the first part of the study, and two achieved
      an accuracy of over 90% in the second part of the study.

PMID- 12227627
TI  - Comparison of heart rate variability analysis methods in patients with
      Parkinson's disease.
AB  - The aim of the present study was to evaluate different analysis methods for
      revealing heart rate variability (HRV) differences between untreated patients
      with Parkinson's disease and healthy controls. HRV in standard cardiovascular
      reflex tests and during a 10 min rest period were measured by time- and frequency
      domain and geometrical and non-linear analysis methods. Both frequency- and time
      domain measures revealed abnormal HRV in the patients, whereas non-linear and
      geometrical measures did not. The absolute high-frequency spectral power of HRV
      was the strongest independent predictor to separate the patients from the
      controls (p = 0.001), when the main time-domain and absolute frequency-domain
      measures were compared with each other. When the corresponding normalised
      spectral units, instead of the absolute units, were used in the comparison, the
      two best single measures for separating the groups were the 30/15 ratio of the
      tilting test (p = 0.003) and the max/min ratio during deep breathing (p = 0.024).
      When the correlations between the different measures were estimated, the time
      domain measures, fractal dimension and absolute spectral powers correlated with
      each other. The frequency- and time-domain analysis techniques of stationary
      short-term HRV recordings revealed significant differences in cardiovascular
      regulation between untreated patients with Parkinson's disease and the controls.
      This confirms cardiovascular regulation failure before treatment in the early
      stages of Parkinson's disease. The HRV spectral powers, in absolute units, were
      the most effective single parameters in segregating the two groups, emphasising
      the role of spectral analysis in the evaluation of HRV in Parkinson's disease.

PMID- 12227628
TI  - Development and in vitro validation of a device for measuring non-shunt cardiac
      output by nitrous oxide throughflow.
AB  - A system has been developed for measuring non-shunt cardiac output by the
      throughflow technique, using nitrous oxide in patients undergoing general
      anaesthesia. The throughflow measurement technique is a non-invasive method based
      on inert gas throughflow theory. In vitro validation of the measurement system
      was performed using a lung gas exchange simulator. The accuracy and precision of
      the throughflow measurement system was assessed by comparing measured and target
      values for five simulated values of non-shunt cardiac output, from 2.88 to 9.86 l
      min(-1). This showed an overall mean bias of -0.031 min(-1) (range -0.00 to 
      0.101 min(-1)), with a mean coefficient of variation of the difference of 1.39%
      (1.20-1.93%). These results indicate that the measurement system is suitable for
      monitoring the non-shunt cardiac output in patients undergoing general
      anaesthesia using nitrous oxide throughflow.

PMID- 12227629
TI  - Circulatory effects of internal jugular vein compression: a computer simulation
      study.
AB  - The effects of compression of the internal jugular veins and the inferior vena
      cava are simulated using an equivalent electronic circuit, which included
      simulation of cardiocirculatory phenomena and special features of the cerebral
      circulation. Compression of the inferior vena cava resulted in a profound
      decrease in cardiac output (from 4.5 to 1.51min(-1)) and arterial pressure (from
      140/85 to 50/35 mmHg). Compression of the internal jugular veins resulted in a
      negligible decrease in cardiac output and arterial pressure, with a cerebral
      blood flow that was slightly decreased. Cerebral capillary and internal jugular
      pressures were considerably increased, leading to obstruction of cerebral veins
      and increased pressure (from 9 to 22 mmHg) and volume (from 120 to 145 ml) of the
      cerebrospinal fluid (CSF). Increased cerebral capsule compliance resulted in
      decreased CSF pressure (from 9 to 8.5 mmHg), but CSF volume increased (from 120
      to 190 ml). A small increase in brain volume (from 1,000 ml to 1,060 ml, 6%
      volume increase) was compensated for by an equal decrease in the volume of CSF.
      When brain volume was above 1,080 ml, the absorption of CSF was reduced, and its
      pressure increased.

PMID- 12227630
TI  - Statistical processing for gastric slow-wave identification.
AB  - Successful identification of gastric slow waves in canine gastric electrical
      activity (GEA) data was achieved using a statistical data-processing procedure
      based on the multiple linear regression (MLR) curve fitting technique. Both
      distal and proximal waveforms were identified, first by construction of separate
      orthonormal bases from pre-selected sets of representative distal and proximal
      gastric slow waves (GSWs). Respective basis matrices were used to fit proximal
      and distal data to an MLR data model. Residual waveforms were computed from the
      original and 'fitted' waveforms and used in identifying GSWs in the data. Canine
      GEA data were split into 1,800-point blocks, and each 245-point data segment in a
      block was processed to identify the GSWs. Gastric slow waves were located in the
      data using a residual mean-squared error (MSE) threshold and, for distal GEA
      data, the minimum value of the main distal waveform peak. All threshold values
      were determined empirically and were set to detect GSWs while limiting false
      matches. Identification rates of 95% and 99% for proximal and distal GSWs,
      respectively, represent a significant improvement over those obtained in a
      previous study in which the same data were analysed using linear signal
      processing methods. The use of the method presented in this paper for real-time
      identification of GSWs in conjunction with an implantable gastric pacer unit
      appears promising. Because the technique is inherently customisable, results
      obtained in this study should also be applicable to human subjects.

PMID- 12227631
TI  - Use of abdominal percussion for pneumoperitoneum detection.
AB  - Pneumoperitoneum refers to free air within the abdominal cavity that typically
      signifies serious abdominal pathology such as a perforated gut. The principal
      hypothesis of the study was that abdominal structure alterations due to
      pneumoperitoneum cause diagnostic changes in the sounds induced by abdominal
      percussion. The current pilot study investigated these changes in a mongrel dog
      model. Abdominal percussion was performed at baseline and after creation of
      pneumoperitoneum states. The resulting acoustic events were acquired, digitised
      and analysed. The event attack and decay rates and dominant frequencies during
      decay decreased with pneumoperitoneum (p = 0.084, 0.014 and 0.004, respectively;
      Wilcoxon signed-rank test). Simple theoretical models were constructed and
      predicted the observed decrease in resonant frequencies with increasing air
      pocket size. The results suggested that the normal and the 1,000 ml
      pneumoperitoneum states can be separated using thresholds of the attack and decay
      rates and resonant frequency (specificity = 80%, 100% and 100%, and sensitivity =
      100%, 100% and 100%, respectively). Separating the control and the 500 ml
      pneumoperitoneum cases may be also possible (specificity = 80%, 100%, 100% and
      sensitivity = 50%, 70% and 90%, respectively), but separating the two levels of
      pneumoperitoneum was not feasible using the current approach. Therefore analysis
      of abdominal percussion sounds may prove useful for pneumoperitoneum detection,
      but not for distinguishing different levels of that condition.

PMID- 12227632
TI  - Linear and non-linear methods for automatic seizure detection in scalp electro
      encephalogram recordings.
AB  - The electro-encephalogram is a time-varying signal that measures electrical
      activity in the brain. A conceptually intuitive non-linear technique, multi
      dimensional probability evolution (MDPE), is introduced. It is based on the time
      evolution of the probability density function within a multi-dimensional state
      space. A synthetic recording is employed to illustrate why MDPE is capable of
      detecting changes in the underlying dynamics that are invisible to linear
      statistics. If a non-linear statistic cannot outperform a simple linear statistic
      such as variance, then there is no reason to advocate its use. Both variance and
      MDPE were able to detect the seizure in each of the ten scalp EEG recordings
      investigated. Although MDPE produced fewer false positives, there is no firm
      evidence to suggest that MDPE, or any other non-linear statistic considered,
      outperforms variance-based methods at identifying seizures.

PMID- 12227633
TI  - Statistical test for peri-stimulus time histograms in assessing motor neuron
      activity.
AB  - The peri-stimulus time histogram is a valuable tool for evaluating neural
      connections in humans. To detect the degree to which a conditioning stimulus to a
      sensory nerve modulates motor neuron activity, a histogram of motor unit spike
      intervals after a conditioning stimulus is measured. This histogram allows the
      effect of the conditioning stimulus to be visualised. By comparison with a
      reference histogram of motor unit spike intervals after a sham stimulus, the
      noise caused by spontaneous firing sway can be removed. However, no valid
      statistical test has yet been developed to separate the physiological effect from
      the spontaneous sway and statistical noise. A computational method has been
      proposed to detect modulation caused by a conditioning stimulus. To clarify the
      effect of a conditioning stimulus, this new method used reference histograms to
      calculate a confidence interval. A simulated experiment demonstrated that about
      2000 re-samplings were sufficient to estimate a confidence interval for a
      histogram with 1 ms bin width constructed from 300 triggers. Testing of the
      experimental data, measured from the tibialis anterior muscles during the
      elicitation of the excitatory spinal reflex, confirmed that significant peaks
      were produced at 30, 34, 35 and 38ms after the conditioning stimulus. These
      correspond appropriately to the delay of the spinal reflex.

PMID- 12227634
TI  - Piezoelectric film transducer for recording of oculography in electro
      encephalogram-polygraphy.
AB  - Oculography is important during clinical electroencephalography (EEG). Routinely,
      silver-silver plate/cup electrodes have been used. However, the electrical
      activity of the anterior parts of the brain can be mixed with the effect of
      eye/eyelid movements. This can result in artifacts disturbing or making it
      impossible to differentiate the frontal activity of the brain from eye movement
      artifacts. Therefore, crystal piezoelectric materials have been used for
      oculography, but they are relatively fragile in practice. In this study we
      present a new type of piezoelectric transducer for the recording of oculography,
      a piezoelectric polyvinylidenefluoride (PVDF) film transducer. Our preliminary
      material consists of routine EEG recordings of 15 subjects performed by means of
      this method. All recordings were of good quality and corresponded well with the
      routine electro-oculography recordings.

PMID- 12227635
TI  - Identification of appropriate primitive polynomials to avoid cross-contamination
      in multifocal electroretinogram responses.
AB  - Abstract-The basis of the multifocal/electroretinogram is the use of a decimated
      m-sequence for simultaneous and independent stimulation of many areas of the
      visual pathway. The purpose of this study was to investigate the effects of cross
      contamination from higher orders of the response. A series of primitive
      polynomials were found by construction of finite fields. The first-order ERG
      response was formed by cross-correlation of m-sequence with the physiological
      response. A second-order response was formed by investigation of particular flash
      sequences of the stimulation sequence and cross-correlation of a second-order m
      sequence with the physiological response. Zech logarithms were used to identify
      cross-contamination between the various first and second-order sequences. Tables
      of good and bad primitive polynomials were constructed for degrees 12-16, and the
      effects of window length and decimation length were examined. When the sequence
      was decimated into 128 areas, and a window of length 16 was examined, cross
      contamination occurred in all sequences generated from primitive polynomials of
      degree less than or equal to 12, but in only 26% of degree 14, and 5.6% of degree
      16. A photodiode (artificial eye) was used in an experiment to construct trace
      arrays showing responses from 61 individual areas. Additional waveforms were
      present on the trace array when the experiment was carried out with a bad
      primitive polynomial. The use of finite field theory to generate primitive
      polynomials and Zech logarithm analysis allowed prediction of which primitive
      polynomials were suitable for m-sequence generation for multifocal
      electroretinography. Practical investigations supported the theoretical analysis.
      This has important implications for developers of multifocal electrophysiology
      systems.

PMID- 12227636
TI  - Inter-chromosome texture as a feature for automatic identification of metaphase
      spreads.
AB  - This paper reports results for a new measure of texture coarseness, as a step
      towards automation of metaphase finding in cell-proliferation studies. This
      measure is highly specific to grey-level inter-chromosome coarseness features in
      microscopic images of metaphase spreads and allows the texture quantification of
      cytological objects, analysing the intensity profile between chromosome-extrema
      samples. Chromosome fragments produce patterns of pixels at low resolution, and
      the local neighbourhood of their individual extrema presents a characteristic
      coarseness along intensity profiles, on randomly oriented test lines. Results of
      the use of this new measure on microscope images of fields of metaphases and
      artifacts are compared with some representative texture measures and the
      performance of reported metaphase finders. This new measure outperforms the
      latter, when applied in metaphase detection and elimination of artifacts. This
      coarseness feature provides a specific metaphase signature that can be used in
      conjunction with other morphological and textural parameters for automated
      metaphase discrimination.

PMID- 12227637
TI  - Human platelet supernatant promotes proliferation but not differentiation of
      articular chondrocytes.
AB  - The objective of the study was to evaluate the growth-promoting activity of human
      platelet supernatant on primary chondrocytes in comparison with fetal calf serum
      (FCS) supplemented cell culture medium. Furthermore, the differentiation
      potential of platelet supernatant was determined in three-dimensional artificial
      cartilage tissues of bovine articular chondrocytes. Proliferation of articular
      and nasal septal chondrocytes was assayed by incorporation of BrdU upon
      stimulation with ten different batches of human platelet supernatant. On bovine
      articular chondrocytes, all these batches were at least as growth-promoting as
      FCS. On nasal septal chondrocytes, nine out of ten batches revealed increased or
      equivalent mitogenic stimulation compared with medium supplemented with FCS.
      Three-dimensional culture and subsequent histological analysis of matrix
      formation were used to determine the differentiation properties of platelet
      supernatant on articular chondrocytes. Human platelet supernatant failed to
      induce the deposition of typical cartilage matrix components, whereas
      differentiation and matrix formation were apparent upon cultivation of articular
      chondrocytes with FCS. Proliferation assays demonstrated that human platelet
      supernatant stimulates growth of articular and nasal septal chondrocytes;
      however, platelet supernatant failed to stimulate articular chondrocytes to
      redifferentiate in three-dimensional chondrocyte cultures. Therefore platelet
      lysate may be suitable for chondrocyte expansion, but not for maturation of
      tissue-engineered cartilage.

PMID- 12227638
TI  - Capsule-substrate contact deformation: determination of adhesion energy.
AB  - A study is reported of a cellular entity (liquid-filled microcapsule) adhered on
      a flat glass substrate in response to changes in osmotic pressure and
      temperature. High-resolution reflection interference contrast microscopy (HR
      RICM) and phase-contrast microscopy were developed for probing the adhesion
      contact area, capsule-substrate separation profile and adhesion energy of the
      adhering microcapsule. The new technique increased the detection limit of the
      measured capsule wall-substrate separation in the cohesive zone from 1 to 4.5
      microm and improved the spatial resolution of the heterogeneous contact zones. A
      theoretical model was applied to correlate quantitatively the adhesion energy to
      the area of the contact zone. The work demonstrated the possibility of
      ascertaining the quantitative interfacial adhesion energy of a liquid-filled
      microcapsule using the present technique and represents the first step in
      extending this novel approach to study more complicated systems, such as cell
      substrate interactions, in the future.

PMID- 12227639
TI  - Approach to the control of entero-haemorrhagic Escherichia coli (EHEC).

PMID- 12227640
TI  - Antimicrobial effect of natural preservatives in a cooked and acidified chicken
      meat model.
AB  - The inhibitory effect of Microgard 100, Microgard 300, nisin, Alta 2002, Perlac
      1902, sodium lactate and essential oil of mustard on microorganisms
      experimentally inoculated was screened in an acidified chicken meat model (pH =
      5.0) and stored for 2 weeks at a none restrictive growth temperature of 22
      degrees C. All antimicrobials tested were used at the highest concentration
      recommended by their manufacturer. Sausage batter made with mechanically deboned
      chicken was inoculated with a mixed culture of Escherichia coli ATCC 25922,
      Brochothrix thermosphacta CRDAV452, and a protective culture Lactobacillus
      alimentarius BJ33 (FloraCan L-2). A final cell concentration of 3-4 log CFU g (
      1) was targeted after cooking at a core temperature of 55 degrees C for each
      microorganism in order to assess cell count variation effectively. Composition,
      water activity (a(w)), pH and redox potential of the sausage model was also
      evaluated. The E. coli population decreased steadily during storage and was close
      or below detection level (< 1 log CFU g (-1)) for all treatments, including the
      control, after 14 days. Sodium lactate was most effective against B.
      thermosphacta; population was 4 log lower than the control after 14 days of
      storage. When essential oil of mustard was used, aerobic mesophilic bacteria and
      lactic acid bacteria were significantly lower than the control after 2 days of
      storage (P < or = 0.05). The other antimicrobial agents tested had no significant
      effect on the aerobic mesophilic bacteria, E. coli, B. thermosphacta and lactic
      acid bacteria counts, when compared to the control.

PMID- 12227641
TI  - PCR amplification of the Salmonella typhimurium fimY gene sequence to detect the
      Salmonella species.
AB  - This study evaluated the suitability of fimY gene amplification by PCR as an
      effective means of detecting Salmonella species. Although fimY gene of Salmonella
      typhimurium is involved in regulating type 1 fimbrial expression, the amino acid
      sequence of FimY shares very little homology with other known prokaryotic
      proteins in the GenBank database. Therefore, fimY is a promising target gene to
      detect the presence of Salmonella species. Herein, two primers internal to the
      fimY gene of S. typhimurium are used to investigate the distribution of the fimY
      homologous sequence among 45 Salmonella serovars and 20 non-Salmonella species by
      using PCR. Experimental results indicated that only Salmonella species possessed
      the fimY homologous sequence, subsequently generating the specific 526-bp DNA
      fragments. The sensitivity of the fmY-specific primer set was demonstrated on a
      Salmonella-free swab sample from a pork carcass surface, which was then
      artificially contaminated with different concentrations of S. typhimurium. A
      combining of pre-enrichment step in buffered peptone water and PCR amplification
      of fimY allowed the detection of S. typhimurium at the concentration of 3.4 x
      10(0) CFU/ml from the swab sample. With an additional enrichment step in
      Rappaport-Vassiliadis (RV) broth, this procedure can also detect pork carcass
      surface naturally contaminated with Salmonella species in a slaughterhouse.
      Results in this study demonstrate that fimY is unique to Salmonella species and
      is an appropriate PCR target for detecting these microorganisms.

PMID- 12227642
TI  - A predictive model that evaluates the effect of growth conditions on the thermal
      resistance of Listeria monocytogenes.
AB  - A predictive model for Listeria monocytogenes was developed using cells grown in
      different pH and milkfat levels before subsequent thermal inactivation in
      identical pH and milkfat conditions. Inactivation of the cells used combinations
      of temperature (55, 60, 65 degrees C), pH (5.0, 6.0, 7.0), and milkfat (0%, 2.5%,
      5.0%) in a complete 3 x 3 x 3 factorial design with each test done in triplicate.
      A modified Gompertz equation was used to model nonlinear survival curves with the
      following three parameter estimates: A for the shouldering region, B for the
      maximum death rate, and C for the tailing region. All treatment sets were
      analyzed together in a regression model using the modified Gompertz equation.
      There was good confidence in the overall model when it was used to predict values
      for the entire data set. The correlation of determination, R2, between the
      observed log surviving fraction (LSF) of cells from each of the conditions
      studied in the experiment, for the overall model was 0.811. For the A and B
      parameter estimates, temperature or milkfat alone, and the interaction of
      temperature and milkfat significantly (p < 0.05) affected the shouldering region
      and maximum death rate of a survival curve, respectively. These results were
      compared to a previously published predictive model, generated for cells grown
      under optimum conditions (pH 7.0, 0% milkfat), where pH was the only significant
      (p < 0.05) factor affecting the shoulder region. These results suggested that the
      conditions of the growth environment had an important impact on survival curve
      shape and the estimates of the predictive model. Specifically, there were more
      factor interactions involving temperature and milkfat level. These growth factors
      affected the shoulder region and maximum rate of death of the survival curve when
      cells were grown in identical medium conditions to which they were heated.
      Differences related to shouldering and inactivation rates for cells grown in
      different conditions may have important and practical importance for estimating
      inactivation of L. monocytogenes. This study provides some evidence on the
      importance of growing conditions when evaluating microbial heat resistance.

PMID- 12227643
TI  - Monte Carlo simulation of the risk of contamination of apples with Escherichia
      coli O157:H7.
AB  - Quantitative descriptions of the frequency and extent of contamination of apple
      cider with pathogenic bacteria were obtained using literature data and computer
      simulation. Probability distributions were chosen to describe the risk of apple
      contamination by each suspected pathway. Tree-picked apples may be contaminated
      by birds infected with Escherichia coli O157:H7 when orchards were located near a
      sewage source (ocean or landfill). Dropped apples could become contaminated from
      either infected animal droppings or from contaminated manure if used as
      fertilizer. A risk assessment model was created in Analytica. The results of
      worst-case simulations revealed that 6-9 log CFU E. coli O157:H7 might be found
      on a harvest of 1000 dropped apples, while 3-4 log CFU contamination could be
      present on 1000 tree-picked apples. This model confirms that practices such as
      using dropped apples and using animal waste as fertilizer increase risk in the
      production of apple cider, and that pasteurization may not eliminate all
      contamination in juice from heavily contaminated fruit. Recently published FDA
      regulations for juices requiring a 5-log CFU/ml reduction of pathogenic bacteria
      in fresh juices should be a fail-safe measure for apples harvested in all but the
      worst-case scenarios.

PMID- 12227644
TI  - Bibliography of food microbiology.

PMID- 12227645
TI  - Study on a novel strategy to treatment of phenylketonuria.
AB  - To replace the low phenylalanine (phe) diet treatment and to improve the quality
      of life of the phenylketonuria (PKU) patients, A phenylalanine ammonia-lyase
      (PAL) cDNA from petroselinum crispum was subcloned into expression vectors,
      pMG36e and pNZ8048, and transformed L. lactis by electroporation. The pMG36e
      PAL/L. lactis and pNZ8048 PAL/L.L. were screened and characterized by using PCR
      and HPLC, and prepared as a liquid type preparation that were given orally to
      treat hyperphenylalaninemia-rats. The phe levels of the rat plasma sample were
      determined by HPLC. The data showed that the plasma phe levels in
      hyperphenylalanemia (HPA) rats receiving preparations made from the engineered L.
      lactis were significantly reduced compared with non-treated HPA rats. The effect
      of the pNZ8048PAL/L.L. showed a higher expression of PAL and better cure results
      than pMG36ePAL/L.L. These results point a potential way for PKU treatment.

PMID- 12227647
TI  - Cellulose amphiphilic adsorbent for the removal of low density lipoprotein.
AB  - Cellulose adsorbent with amphiphilic ligands for adsorption of low density
      lipoprotein (LDL) was prepared by the following procedures: Cellulose beads were
      reacted with cholesterol N-(6-isocyanatohexyl) carbamate in the presence of
      pyridine in DMSO at 80 degrees C in order to introduce the hydrophilic moiety, it
      was then reacted with chlorosulfonic acid in dimethyl formamide, which introduced
      the sulfonic group. Adsorption capacity of adsorbent was studied, which showed
      the removal of LDL, TC, TG to be 0.857 mg/ml, 1.317 mg/ml, 1.002 mg/ml
      respectively without significantly affecting total protein levels in the plasma.
      Moreover, it has a better selectivity in removing LDL, TC, TG compared with
      cellulose adsorbent with only hydrophobic or hydrophilic ligand.

PMID- 12227646
TI  - Effect of diaspirin crosslinked hemoglobin (DCLHb HemAssist) during high blood
      loss surgery on selected indices of organ function.
AB  - BACKGROUND: The safety of the hemoglobin based oxygen carrier diaspirin
      crosslinked hemoglobin (DCLHb) has been reported only in the low (50-200 mg/kg)
      dose range [Przybelski. R.J.; Daily, E.K.; Kisicki, J.C.; Mattia-Goldberg, C.;
      Bounds, M.J.; Colburn, W.A. Phase I study of the safety and pharmacologic effects
      of diaspirin crosslinked hemoglobin solution. Crit. Care Med. 1996, 24 (12), 1993
      2000, Bloomfield, E.; Rady, M.; Popovich, M.; Esfandiari, S.; Bedocs, N. The use
      of diaspirin crosslinked hemoglobin (DCLHb 1996, 95, (3A), A220.]. We conducted a
      randomized prospective open-label trial of DCLHb and packed red blood cells
      (PRBCs) in high-blood loss surgical patients to show the effect of 750 ml DCLHb
      (approximately 1000 mg/kg) on selected indices of organ function. METHOD: After
      institutional approval, 24 patients scheduled to undergo elective orthopedic or
      abdominal surgery, were randomized to receive either PRBCs or 10% DCLHb within 12
      hours after the start of surgery. Patients with renal insufficiency, abnormal
      liver function, severe coronary artery disease (CAD) and ASA physical status > or
      = IV were excluded. The anesthetic technique was left to the judgment of the
      anesthesiologist. Autologous predonation and intraoperative blood conservation
      techniques were utilized as appropriate. The indications for blood transfusion
      were individualized on disease state, stage of surgery, and plasma Hb
      concentration. Laboratory studies were obtained preoperatively and up to 28 days
      postoperatively. Patients were observed daily for development of jaundice,
      hematuria, nausea, vomiting, gastrointestinal discomfort, cardiac, respiratory,
      and infectious complications. Organ effects were assessed with urinalysis,
      creatinine clearance, electrocardiogram (ECG), and a panel of blood and serum
      laboratory tests. RESULTS: The dose of DCLHb administered ranged from 680-1500
      mg/kg (mean = 999 mg/kg). Estimated blood loss was 27 +/- 13 ml/kg and 31 +/- 15
      ml/kg in the control and DCLHb groups, respectively. Fewer PRBCs (1.9 +/- 1.2 vs.
      3.4 +/- 2.4 units. P = 0.06) were transfused to DCLHb patients on the operative
      day although this difference was no longer apparent later on. In the DCLHb group,
      4/12 patients avoided any allogeneic PRBC transfusion vs. none in the control
      group (P = 0.09). Systolic, diastolic and mean blood pressure increased
      moderately after DCLHb for a period of 24-30 hours. There were no occurrences of
      cardiac ischemia. myocardial infarction, stroke, or pulmonary edema, by clinical
      or laboratory parameters up to the 28th postoperative day (POD). Seven of 12
      (58%) DCLHb patients had yellow skin discoloration vs. none in the PRBC group (P
      < 0.01). Two of four non-urologic surgery patients developed asymptomatic
      postoperative hemoglobinuria after DCLHb. Creatinine clearance was unchanged
      postoperatively. Because of hemoglobin interference, bilirubin, gamma-glutamyl
      transferase (GGT), and amylase could not be measured reliably on POD1; on POD2.
      amylase was transiently elevated to 3 times ULN along with mild elevations of
      bilirubin, transaminases and BUN. Mean total creatine phoshokinase (CPK) peaked
      at 8 times the upper limit of normal (ULN) in the DCLHb group, compared with less
      than twice ULN for controls. Three DCLHb patients had prolonged ileus. Two of
      these patients had postoperative hyperamylasemia, one of whom developed mild
      pancreatitis. DCLHb did not affect white blood cell count or coagulation tests.
      CONCLUSION: Administration of approximately 1000 mg/kg DCLHb was associated with
      transient arterial hypertension, gastrointestinal side effects, laboratory
      abnormalities, yellow skin discoloration, and hemoglobinuria. These observations
      point to opportunities for improvement in future synthetic hemoglobin design.

PMID- 12227648
TI  - Immobilization of Spirulina subsalsa for removal of triphenyltin from water.
AB  - Spirulina subsalsa is immobilized with alginate, which increases the growth rate,
      chlorophyll content, phycocyanin content and nitrate reductase activity.
      Immobilized Spirulina subsalsa with alginate increases absorption of triphenyltin
      chloride (TPT). The phycocyanin of immobilized Spirulina subsalsa is more
      sensitive to TPT then free alga. The immobilization enhances the toxic effect of
      TPT on nitrate reductase activity of Spirulina subsalsa. Experimental results
      demonstrate that the immobilization of Spirulina subsalsa is feasible. Removal of
      TPT by immobilized Spirulina subsalsa reaches 68%. Biosorption mechanism of TPT
      by Spirulina subsalsa should be further studied.

PMID- 12227649
TI  - Bioconversion of domestic wastewater sludge by immobilized mixed culture of
      penicillum Corylophilum WWZA1003 and Aspergillus niger SCahmA103.
AB  - The bioconversion of domestic wastewater sludge by immobilized mixed culture of
      filamentous fungi was investigated in a laboratory. The potential mixed culture
      of Penicillium corylophilum WWZA1003 and Aspergillus niger SCahmA103 was isolated
      from its local habitats (wastewater and sludge cake) and optimized on the basis
      of biodegradability and dewaterability of treated sludge. The observed results in
      this study showed that the sludge treatment was highly influenced by the effect
      of immobilized mixed fungi using liquid state bioconversion (LSB) process. The
      maximum production of dry filter cake (DFC) was enriched with fungal biomass to
      about 20.05 g/kg containing 23.47 g/kg of soluble protein after 4 days of fungal
      treatment. The reduction of COD, TSS, turbidity (optical density against
      distilled water, 660 nm), reducing sugar and protein in supernatant and
      filtration rate of treated sludge were influenced by the fungal mixed culture as
      compared to control (uninnoculated). After these processes, 99.4% of TSS, 98.05%
      of turbidity, 76.2% of soluble protein, 98% of reducing sugar and 92.4% of COD in
      supernatant of treated sludge were removed. Filtration time was decreased
      tremendously by the microbial treatment after 2 days of incubation. The effect of
      fungal strain on pH was also studied and presented. Effective bioconversion was
      observed after 4 days of fungal treatment.

PMID- 12227650
TI  - The modification of scaffold material in building artificial dermis.
AB  - Type X collagen is principal extracellular matrix (ECM) in natural dermis. To
      prepare artificial dermis, collagen is traditional, and most superior
      biomaterial. But beside collagen, the dermis also contains many other ECM. Among
      them, glycosaminoglycan (GAG) is another important substance. To imitate the
      natural dermis, and modificate the scaffold materials, two types of scaffolds
      were prepared: one is traditional type X collagen spongy scaffold, the other is
      collagen-chondroitin sulfate (CS) spongy scaffold. Collagen was blended with CS,
      one kind of GAG, and cross-linked by 1-ethyl-3-(3-dimethyl aminopropyl)
      carbodiimide (EDC). Dermis fibroblast was isolated from neonate prepuce, and
      dermis fibroblasts were cultured on the scaffolds. The physical and chemical
      properties of the scaffolds were tested, including SEM, DSC, H&E staining,
      immunohistochemical staining and CS content analysis and so on. The results
      indicated that EDC is an effective and non-cytotoxic cross-link reagent, and
      attaching CS into collagen scaffold could improve the stability and
      histocompatibility of scaffold.

PMID- 12227651
TI  - New insights into gastrointestinal and liver diseases based on molecular aspects
      of transport physiology.

PMID- 12227652
TI  - Not all absent serum ceruloplasmin is Wilson disease: a review of
      aceruloplasminemia.

PMID- 12227653
TI  - Iron transport and hemochromatosis.

PMID- 12227655
TI  - NIH postdoubling budgets represent a challenge, Zerhouni says.

PMID- 12227656
TI  - Bush administration quietly approves fetal stem cell work: funding allowed
      despite federal limits on embryo use.

PMID- 12227654
TI  - Idiopathic pancreatitis related to CFTR: complex inheritance and identification
      of a modifier gene.
AB  - Idiopathic chronic pancreatitis (ICP) is the leading cause of nonalcoholic
      chronic pancreatitis. This study examined a series of patients with ICP to
      determine the prevalence and role of mutations of the cystic fibrosis gene (CFTR)
      and of a trypsin inhibitor gene (PSTI). Genetic testing was done in 39 patients
      with ICP. In this series, 17 patients had CFTR mutations and 9 had PSTI
      mutations. Pancreatitis risk was increased 14-fold by having the N34S PST1
      mutation, 40-fold by having two abnormal copies of CFTR, and 600-fold by having
      both. In patients with two CFTR mutations, extrapancreatic clinical findings and
      nasal bioelectric responses suggested reduced residual CFTR protein function.
      Thus, pancreatitis risk showed complex inheritance and was highest in individuals
      who have abnormalities in both the pancreatic ducts (CFTR) and acini (PSTI).
      These findings indicate that PSTI is a modifier gene for CFTR-related ICP and
      have implications for the classification, diagnosis, and pathogenesis of
      pancreatitis.

PMID- 12227657
TI  - Scientists petition president's bioethics panel on stem cell nuclear transfer
      research moratorium recommendation.

PMID- 12227658
TI  - Top biotechnology regions entrenched: more than good research is needed to
      succeed, Brokings study finds.

PMID- 12227659
TI  - The nocturnal serum thyrotropin surge is inhibited in patients with adrenal
      incidentaloma.
AB  - BACKGROUND: Alterations in hypothalamic-pituitary function have been described in
      patients with incidentally discovered adrenal adenomas and have been attributed
      to their subtle hypercortisolemic status. METHODS: To establish whether the
      central control of the hypothalamic-pituitary-thyroid axis is altered in these
      endocrine conditions, the nocturnal (10:30 PM-2:00 AM) serum thyroid-stimulating
      hormone (TSH) surge (measured by dividing the difference between nighttime and
      morning TSH values by the morning TSH value and then multiplying by 100), the TSH
      response to thyrotropin-releasing hormone (200 microg as an intravenous bolus)
      and serum free thyroid hormone levels were evaluated in patients with adrenal
      incidentaloma (experimental group) and in normal controls (control group).
      Urinary free cortisol concentrations were also measured. RESULTS: The nocturnal
      TSH surge was observed in the normal controls, whereas it was inhibited in the
      patients of the experimental group. Serum free triiodothyronine levels were
      similar in the two groups, whereas the TSH response to thyrotropin-releasing
      hormone was significantly lower in the experimental than in the control group.
      Urinary free cortisol levels were significantly higher in the experimental group.
      CONCLUSION: These data indicate that even conditions of slight glucocorticoid
      excess may exert inhibitory effects on TSH secretion, which suggests the presence
      of a slight central hypothyroidism in patients with adrenal incidentaloma.

PMID- 12227660
TI  - Streamlining the clinical research enterprise.

PMID- 12227661
TI  - Over half a century of playing with inkblots and other wondrous pursuits.
AB  - This invited autobiography focuses on the highlights in the career of a
      psychologist who has devoted over a half century to personality assessment, among
      other lifetime pursuits. Beginning with an introduction to my early years growing
      up in Chicago, the story continues through World War II when, as a naval officer,
      I developed a late-blooming interest in coping behavior and reactions to stress.
      As with many other post-war graduate students, inkblots held a particular
      fascination for me as an indirect means of assessing personality and
      psychopathology through perception. A successful dissertation followed by
      fellowships and grants over several decades made possible the development of the
      Holtzman Inkblot Technique (HIT). Published in 1961 by the Psychological
      Corporation, the HIT consists of two parallel forms containing 45 test blots
      each. It has been used in hundreds of research studies and in clinical practice
      as an alternative to the Rorschach throughout the world. In addition to work on
      the HIT, I describe my efforts to expand personality assessment and psychological
      research into the international arena and provide a summary of activities in
      administration and public service.

PMID- 12227662
TI  - A taxometric analysis of the MMPI-2 Depression scales.
AB  - The MMPI (Hathaway & McKinley, 1943) and MMPI-2 (Butcher et al., 2001) have long
      been used as measures of psychopathology. Both clinicians and researchers have
      noted the widespread existence of negative affectivity on the MMPI and MMPI-2
      that may elevate scale scores and eclipse the tests' ability to differentiate
      depression from other clinical disorders. Using taxometric analyses, in this
      study we sought to test directly whether the MMPI-2 depression scales could
      differentiate patients with depressive symptoms from patients with other
      disorders. A large psychiatric sample (N = 2,000) was utilized and analyses were
      run separately for men and women. Taxometric analyses did not find a MMPI-2
      Depression scale cut point that categorizes patients with depressive symptoms
      from other patients. Rather, these findings support previous studies finding an
      underlying dimensionality of depression. We discuss implications for MMPI-2 scale
      use and depression nosology in light of these findings.

PMID- 12227663
TI  - Rorschach variables related to blood glucose control in insulin-dependent
      diabetes patients.
AB  - In this article, we explored relations between selected Rorschach variables and
      blood glucose control in Insulin-Dependent Diabetes Mellitus (IDDM) patients.
      Three domains of psychological functioning are taken into consideration:
      emotional distress, coping and problem solving, and cognitive efficiency. Seventy
      one IDDM patients (38 men, 33 women; mean age 42.2 +/- 14.9 years) from an
      outpatient unit took the Rorschach Comprehensive System (Exner, 1986). Nine
      variables were selected as independent variables. Blood glucose, a dependent
      variable, was measured by the proportion of glycated hemoglobin. Results of 2
      regression analyses show that Y and C' correlate to higher blood glucose. WSum C
      and the absence of texture related to lower levels of blood glucose. A
      confounding effect of complications was observed. The findings suggest that
      emotional factors should be accorded greater attention in behavioral self
      regulations in diabetes.

PMID- 12227664
TI  - A Rorschach study of oral dependence in alcoholics and depressives.
AB  - Despite the strong association between alcoholism and orality in psychoanalytic
      theory, use of the Rorschach Inkblot Test to provide empirical support for such a
      link has yielded decidedly mixed results. However, Masling's Rorschach Oral
      Dependency (ROD) scale has shown twice that people with alcoholism give more oral
      dependent responses on the Rorschach than matched comparison groups (Bertrand &
      Masling, 1969; Weiss & Masling, 1970), which is supportive of classical analytic
      theory. In this study, we investigated alcohol groups, depression groups, and
      "normal" undergraduates with the ROD scale and found that the 2 clinical groups
      produced higher ROD scores than the undergraduates. In addition, recent studies
      by Duberstein and Talbot (1993) and Fowler, Hilsenroth, and Handler (1996)
      provide evidence for an object relations model of dependency that suggests that a
      balance between anaclitic dependence and complete independence, in which
      dependency needs are acknowledged but are not overwhelming, is most adaptive.
      This model of dependency was evaluated; it was found that a simple difference in
      group means provided a better fit with the data, although some evidence of an
      object relations model also was found. Finally, Rorschach and MMPI-2 (Butcher,
      Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) levels of general defensiveness and
      primary process manifestations in Rorschach content were investigated to assess
      whether participants were responding defensively to the testing and whether there
      were any differences in the nature of oral-dependent responses between the
      clinical groups.

PMID- 12227665
TI  - The incremental validity of passive-aggressive personality symptoms rivals or
      exceeds that of other personality symptoms in suicidal outpatients.
AB  - We examined the incremental validity of passive-aggressive and other personality
      symptoms, by determining personality syndromes' ability to account for unique
      variance in distress and impairment as indexed by several Axis I-related
      symptoms. Two hundred fifty young adults, referred for suicidal behavior or
      ideation, completed the Millon Clinical Multiaxial Inventory (Millon, 1983) as
      well as several other symptom measures. The personality syndromes varied
      considerably in their ability to account for unique variance in Axis I-related
      symptoms. Several syndromes, including schizoid, schizotypal, and compulsive
      symptoms, showed relatively low incremental validity, whereas the incremental
      validity of passive-aggressive symptoms exceeded all others. The criterion of
      incremental validity represents an inclusive and persuasive means to evaluate
      personality disorder validity. On this criterion, passive-aggressive symptoms
      display high validity, and passive-aggressive personality disorder, in some form,
      may deserve inclusion on Axis II of future editions of Diagnostic and Statistical
      Manual of Mental Disorders (American Psychiatric Association).

PMID- 12227666
TI  - Elaboration of some sequence analysis strategies: examples and guidelines for
      level of confidence.
AB  - Although not the only way to approach the interpretation of Rorschach test data,
      the Comprehensive System (Exner, 1991) search strategy is the most systematized
      and empirically informed to date. Within that search strategy, a role for
      sequence analysis remains (Weiner, 1998). Sequence analysis adds a specificity of
      nuance useful in bringing personal meaning to, answering more difficult test
      questions about, or explaining apparent incongruities in the data. In this
      article, I elaborate a few aspects of some particular sequence analysis
      strategies as a way of supplementing Weiner's (1998) description. I discuss and
      expand the following ideas: (a) conjoint (configurational) examination of
      individual responses, (b) specifics about patient concerns, (c) specifics about
      response deterioration and their treatment implications, (d) specifics about
      response recovery and their treatment implications, (e) contribution of attitude
      toward the response, (f) minisequence and configurational analysis strategies for
      particular test questions, and (g) guidelines for establishing level of
      confidence in sequence analysis inferences.

PMID- 12227667
TI  - Rorschach training: doctoral students' experiences and preferences.
AB  - American Psychological Association graduate student affiliates (500) were sent
      surveys regarding their Rorschach training experiences and interests. From 254
      valid surveys, 87% of students reported that they were offered an introductory
      course that included the Rorschach; only about one fourth of the students were
      offered an advanced course. Of the students (212) who had some Rorschach
      training, the majority (78%) indicated they would like to obtain more. Most
      students viewed the Rorschach as helpful for understanding a client's
      personality. More training is needed, however, in applying this understanding to
      treatment planning and client feedback. Students were more satisfied with their
      training when they (a) had more Rorschach experience (didactic, practical, and
      research familiarity), (b) were in a psychodynamic or eclectic versus cognitive
      behavioral program, (c) were pursuing a clinical PsyD versus clinical PhD, and
      (d) perceived a more positive attitude toward the Rorschach in their training
      program. All of these variables (including training satisfaction) also were
      related to students' expected likelihood of using the Rorschach in their
      professional careers.

PMID- 12227668
TI  - Positive and negative symptoms of schizotypy and the Five-factor model: a domain
      and facet level analysis.
AB  - In this study, we investigated the Five-factor model in the concurrent prediction
      of positive symptom schizotypy as measured by the Magical Ideation (Eckblad &
      Chapman, 1983) and Perceptual Aberration (Chapman, Chapman, & Raulin, 1978)
      scales and negative symptom schizotypy as measured by the Physical Anhedonia
      (Chapman, Chapman, & Raulin, 1976) and Revised Social Anhedonia (Eckblad,
      Chapman, Chapman, & Mishlove, 1982; Mishlove & Chapman, 1985) scales. Previous
      studies suggest that these measures reflect the core symptoms found in
      schizotypal and schizoid personality disorder (Bailey, West, Widiger, & Freiman,
      1993). Negative symptoms were significantly predicted by Neuroticism (+),
      Extraversion (-), Openness (-), and Agreeableness (-) domains of the Revised NEO
      Personality Inventory (NEO-PI-R; Costa & McCrae, 1992). Additionally, positive
      symptoms were significantly predicted by Neuroticism (+), Openness (+), and
      Agreeableness (-). In addition, we examined the validity of lower order traits in
      de- scribing these symptoms of character pathology. These findings lend further
      support for the use of domain and facet scales of the NEO-PI-R in the
      identification of personality pathology.

PMID- 12227669
TI  - The Personality Assessment Inventory Drug Problems Scale: a validity analysis.
AB  - An analysis of the relationship among the Personality Assessment Inventory (PAI;
      Morey, 1991, 1996) Drug Problems (DRG) scale scores, the Addiction Severity Index
      (ASI; McLellan et al., 1992) scores, and urine toxicology reports revealed that
      the PAI Drug Problem scale scores of 100 substance-using and substance-abusing
      men and women were distributed in a manner that was in agreement with the
      guidelines suggested by Morey (1991, 1996) in the PAI manual. There were
      significant correlations among the PAI DRG scale and the ASI scales related to
      frequency of use, negative consequences of use, and need and desire for
      treatment. Overall, higher scores did reflect both more serious involvements with
      drug use and more serious problems as a consequence of their involvement.

PMID- 12227670
TI  - Narcissism and depression: MMPI-2 evidence for the continuum hypothesis in
      clinical samples.
AB  - According to one hypothesis, self-report measures of narcissism help describe a
      psychological continuum related to self-esteem. Most of the previous support for
      this idea appeared in studies of undergraduates responding to the Narcissistic
      Personality Inventory (NPI; Raskin & Hall, 1981) along with other self-report
      instruments. In this project, results consistent with the continuum hypothesis
      were obtained when Minnesota Multiphasic Personality Inventory-2 (MMPI-2;
      Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) narcissism scales were
      correlated with depression in adults receiving treatment for alcoholism.
      Essentially identical outcomes emerged in a second sample of state psychiatric
      hospital patients. A third study upheld the hypothesis when narcissism scales
      were correlated with clinical assessments rather than self-reports of depression.
      None of these findings were easily explained in terms of alternative
      interpretations of self-reported narcissism, and these data demonstrate that
      empirical support for the continuum hypothesis was not limited to the NPI,
      undergraduates, or self-report measures.

PMID- 12227671
TI  - Workers as research subjects: a vulnerable population.
AB  - Workers should be considered as a vulnerable human subjects research population
      since they require special protections. The Code of Federal Regulations "Common
      Rule for the Protection of Human Subjects in Research" does not offer adequate
      definition of this issue. Currently there is no formal ethical framework that
      addresses the unique vulnerability of workers (or former workers) who participate
      in research studies. This article addresses this concern and is based on a larger
      report published by the U.S. Department of Energy. Further, even though workers
      may be study subjects for legitimate political, social, and scientific reasons,
      meritorious science and adherence to the Common Rule must be the expectation.

PMID- 12227672
TI  - Audiometric findings in workers exposed to low levels of styrene and noise.
AB  - Audiometry and exposure measurements were conducted on workers from fiberglass
      and metal products manufacturing plants and a mail distribution terminal (N =
      313). Workers exposed to noise and styrene had significantly worse pure-tone
      thresholds at 2, 3, 4, and 6 kHz when compared with noise-exposed or nonexposed
      workers. Age, noise exposure, and urinary mandelic acid (a biologic marker for
      styrene) were the variables that met the significance level criterion in the
      multiple logistic regression. The odds ratios for hearing loss were 1.19 for each
      increment of 1 year of age (95% confidence interval [CI], 1.11-1.28), 1.18 for
      every decibel >85 dB(A) of noise exposure (95% CI, 1.01-1.34), and 2.44 for each
      millimole of mandelic acid per gram of creatinine in urine (95% CI, 1.01-5.89).
      Our findings suggest that exposure to styrene even below recommended values had a
      toxic effect on the auditory system.

PMID- 12227673
TI  - Does standing at work during pregnancy result in reduced infant birth weight?
AB  - The purpose of this study was to investigate the association between infant birth
      weight and standing at work during pregnancy. A total of 1222 pregnant women
      employed in a large petrochemical corporation in Beijing, China, were enrolled in
      the study, after receiving permission from the government to have a child. The
      subjects were followed up from that time through their entire pregnancy, for a
      total of up to 12 months. All subjects delivered at the company staff hospital
      between 1996 and 1998. Various work-related physical activities during pregnancy
      were assessed using a structured questionnaire, and generalized additive models
      (GAMs) were performed to examine their association with birth weight. Of the
      assessed activities, only standing was significantly associated with birth
      weight. After adjusting for potential confounders, maternal standing hours per
      day at work was found to be significantly associated with reduced birth weight (
      17.7 g, P = 0.03).

PMID- 12227674
TI  - Productivity losses related to the common cold.
AB  - Health-related productivity assessments typically focus on chronic conditions;
      however, acute conditions, particularly colds, have the potential to cause
      substantial health-related productivity losses because of their high prevalence
      in working-age groups. This article presents the findings of a study conducted to
      estimate productivity loss due to cold by using a telephone-administered survey
      that measured three sources of loss: absenteeism, on-the-job productivity, and
      caregiver absenteeism. Each cold experienced by a working adult caused an average
      of 8.7 lost work hours (2.8 absenteeism hours; 5.9 hours of on-the-job loss), and
      1.2 work hours were lost because of attending to children under the age of 13 who
      were suffering from colds. We conclude that the economic cost of lost
      productivity due to the common cold approaches $25 billion, of which $16.6
      billion is attributed to on-the-job productivity loss, $8 billion is attributed
      to absenteeism, and $230 million is attributed to caregiver absenteeism.

PMID- 12227675
TI  - Impact of the coronary health improvement project (CHIP) on several employee
      populations.
AB  - The greatest potential to improve public health lies in the ability of
      individuals to adopt healthful behaviors. The purpose of this study was to
      determine whether participation in a facilitator-based video version of the
      Coronary Health Improvement Project (CHIP) would improve health behaviors and
      significantly reduce employee health risks. Employees (n = 442) from six
      worksites in metropolitan Rockford, Illinois, were used in a pretest/posttest
      design. Employees self-selected to participate in a facilitator-based, CHIP video
      program. Participants received instruction twice a week, for 8 weeks, via 15
      videos shown at each participating worksite. Demographic and biometric data (body
      weight, body mass index, blood lipids, blood pressure, and fasting blood glucose)
      were evaluated at baseline and at 8 weeks. All sites individually and
      collectively demonstrated significant and meaningful reductions in body weight,
      body mass index, total cholesterol, low-density lipoprotein cholesterol,
      triglycerides, and fasting blood glucose. Men demonstrated greater improvement
      than women, and individuals with higher baseline health risks experienced the
      greatest reductions in risk. The CHIP video program appears to be an effective
      method of lowering employee health risks. Future research is needed to determine
      how long these reductions may persist.

PMID- 12227676
TI  - Lipid profile of firefighters over time: opportunities for prevention.
AB  - Heart disease is the primary cause of on-duty deaths in firefighters, but little
      is known about their lipid profile. We evaluated the lipid profile in relation to
      other cardiovascular disease risk factors in 321 firefighters at a baseline
      examination. Prospective comparisons were performed for 285 firefighters, who
      were enrolled in a statewide medical surveillance program, and had complete
      follow-up data for 4 years. The average cholesterol level in firefighters
      declined from 224 mg/dL at baseline (1996-1997) to 214 mg/dL at the follow-up
      examination (P < 0.0001). Conversely, both obesity (body mass index > or = 30;
      34% versus 40%, P = 0.008) and triglycerides (> or = 200 mg/dL; 27% versus 35%, P
      = 0.047) increased over time. The proportion of firefighters taking lipid
      lowering medications increased from 3% at baseline to 12% at follow-up (P <
      0.0001). Cholesterol levels declined significantly, and treatment rates for
      elevated cholesterol increased over time. Despite repeated examinations, a
      considerable number of firefighters had persistently elevated cholesterol, and
      only a minority were receiving adequate treatment.

PMID- 12227677
TI  - Sun-related behaviors of outdoor working men with a history of non-melanoma skin
      cancer.
AB  - The present study describes sun exposure and sun protection behaviors of northern
      Australian outdoor workers with previous non-melanoma skin cancer (NMSC). In 1999
      a cross-sectional study of northern Australian men with previous NMSC was
      conducted by self-administered questionnaire. Compared to other men, outdoor
      workers spent more time in the sun on average working days and days off (P <
      0.0001, respectively), and outdoor workers with sun-sensitive skin reported that
      more skin lesions had been removed (P = 0.0461). The workplace did not reinforce
      sun-safe practices of 36.8% of workers who spent half their time or more
      outdoors. Sun-protective behaviors were not different between in- and outdoor
      workers. Outdoor workers experienced high levels of sun exposure, however, sun
      protective behavior was similar to other workers. Workplaces should be targeted
      to reinforce sun-safe policies.

PMID- 12227678
TI  - Brainstem neural conduction biomarkers in lead-exposed children of Andean lead
      glaze workers.
AB  - Pediatric lead (Pb) intoxication remains a major medical challenge in some
      developing countries where Pb is used in glazing industries. Pb exposure is
      reported to induce neurophysiological and neurocognitive impairment in children.
      However, the threshold and level of Pb intoxication necessary to induce
      neuropathology have not been established. Brainstem auditory evoked responses
      (BAERs) have been used widely as a sensitive biomarker for Pb-induced
      neurotoxicity. In this field study, BAER neural conduction time was used as a
      biomarker for central nervous system impairment in Andean children living in
      areas of high Pb contamination from Pb-glazing cottage industries. The mean Pb
      level in blood (PbB) for 112 Pb-exposed children was 49.25 microg/dL (SD, 270
      microg/dL range, 4.4-119.1 microg/dL). Although BAERs in some children showed
      prolongations in neural conduction times, regression analyses revealed no
      significant correlation between PbB levels and BAER interpeak conduction times
      for 112 replicate recordings (I-III, r = 0.008, P = 0.93; II-V, r = 0.13, P =
      0.16; I-V, r = 0.09, P = 0.35; and I-VI, r = 0.14, P = 0.27). A subgroup of 69
      children in the study area with PbB levels in the United States Centers for
      Disease Control and Prevention (CDC) medical intervention-emergency
      classifications (CDC IV and V; mean, 67.0 microg/dL, SD, 15.8 microg/dL; range,
      45.1-119.1 microg/dL) showed no significant correlation between PbB and BAER
      interpeak interval and no significant differences in BAER than a normal subgroup
      (t test, P > 0.05). The results demonstrate some evidence of abnormal possibly Pb
      induced neural conduction delays in some individual children but a remarkable
      overall neurobiological functioning in severe, chronic pediatric Pb intoxication
      without measurable impairment of brainstem auditory nuclei and tracts, as
      evidenced by neurophysiological conduction times. The findings also demonstrate
      the variability in the threshold level and duration of Pb exposure necessary to
      induce brainstem neuropathology.

PMID- 12227679
TI  - Development of an agricultural job-exposure matrix for British Columbia, Canada.
AB  - Farmers in British Columbia (BC), Canada have been shown to have unexplained
      elevated proportional mortality rates for several cancers. Because agricultural
      exposures have never been documented systematically in BC, a quantitative
      agricultural Job-exposure matrix (JEM) was developed containing exposure
      assessments from 1950 to 1998. This JEM was developed to document historical
      exposures and to facilitate future epidemiological studies. Available information
      regarding BC farming practices was compiled and checklists of potential exposures
      were produced for each crop. Exposures identified included chemical, biological,
      and physical agents. Interviews with farmers and agricultural experts were
      conducted using the checklists as a starting point. This allowed the creation of
      an initial or 'potential' JEM based on three axes: exposure agent, 'type of work'
      and time. The 'type of work' axis was determined by combining several variables:
      region, crop, job title and task. This allowed for a complete description of
      exposures. Exposure assessments were made quantitatively, where data allowed, or
      by a dichotomous variable (exposed/unexposed). Quantitative calculations were
      divided into re-entry and application scenarios. 'Re-entry' exposures were
      quantified using a standard exposure model with some modification while
      application exposure estimates were derived using data from the North American
      Pesticide Handlers Exposure Database (PHED). As expected, exposures differed
      between crops and job titles both quantitatively and qualitatively. Of the 290
      agents included in the exposure axis; 180 were pesticides. Over 3000 estimates of
      exposure were conducted; 50% of these were quantitative. Each quantitative
      estimate was at the daily absorbed dose level. Exposure estimates were then rated
      as high, medium, or low based on comparing them with their respective oral
      chemical reference dose (RfD) or Acceptable Daily Intake (ADI). This data was
      mainly obtained from the US Environmental Protection Agency (EPA) Integrated Risk
      Information System database. Of the quantitative estimates, 74% were rated as low
      (< 100%) and only 10% were rated as high (>500%). The JEM resulting from this
      study fills a void concerning exposures for BC farmers and farm workers. While
      only limited validation of assessments were possible, this JEM can serve as a
      benchmark for future studies. Preliminary analysis at the BC Cancer Agency (BCCA)
      using the JEM with prostate cancer records from a large cancer and occupation
      study/survey has already shown promising results. Development of this JEM
      provides a useful model for developing historical quantitative exposure estimates
      where is very little documented information available.

PMID- 12227680
TI  - Non-Hodgkin's lymphomas and organic solvents.
AB  - Organic solvents have been suggested as a possible risk factor for non-Hodgkin's
      lymphomas (NHL). We studied 109 NHL incident cases and 276 controls with other
      cancers (1990/1996) in the city of Salvador, Brazil. Occupational exposure to
      organic solvents was evaluated through standardized questionnaires and defined by
      industrial hygienists, taking into account individuals' lifetime history. An
      association between occupational exposure to organic solvents and NHL was
      observed, OR = 1.67 (95% CI, 0.97 to 2.87), especially among individuals less
      than 64 years, OR = 1.91 (95% CI, 0.99 to 3.67), and among those who used
      domestic insecticides, OR = 2.24 (95% CI, 1.01 to 3.97). Odds ratios were similar
      for nodal and diffuse NHL. These results suggest that organic solvents may
      contribute to the causation of NHL, especially among young individuals, and that
      synergism may play a role in the process of lymphomagenesis.

PMID- 12227682
TI  - Contrast-enhanced MR urography in the evaluation of renal transplants with
      urological complications.
AB  - AIM: The diagnostic work-up of renal transplants with impaired function due to
      urological problems can be difficult. This study was performed to assess
      sensitivity and specificity of non-invasive contrast-enhanced MR urography (MRU).
      METHODS AND MATERIALS: Thirty-five patients with renal transplants (25 - 71
      years, mean: 53.4 years) with sonographically diagnosed hydronephrosis or
      perirenal fluid collections were assessed by MR urography. MR examinations were
      carried out at a 1.5 T clinical scanner (Vision, Siemens, Erlangen, Germany) with
      a 512 matrix contrast-enhanced fat-suppressed T1-weighted FLASH 3D sequence in
      breath-hold technique. MIP reconstructions were used to produce MR urography. MRU
      diagnoses were compared to operative results. RESULTS: In all patients, images
      with sufficient contrast in the renal collecting system were obtained.
      Hydronephrosis was confirmed in 20 patients, 8 patients showed a different
      pathology while 7 had normal findings. Compared to operative results, sensitivity
      of MRU was 100% with a specificity of 78%, respectively. One ureteral stone was
      misdiagnosed as a stricture, and 2 suspected ureteral stenoses could not be found
      upon operation. CONCLUSIONS: Contrast-enhanced MR urography is a highly sensitive
      and specific non-invasive method to evaluate patients suspected of having typical
      post-transplant urological complications. It may replace invasive procedures such
      as antegrade pyelography in the pre-operative work-up.

PMID- 12227683
TI  - Simultaneous bilateral quadriceps tendon rupture in renal patients.
AB  - AIMS: Simultaneous bilateral quadriceps tendon rupture occurs in patients with
      renal disease. It has been hypothesized that the length of renal disease and the
      length of dialysis may correlate with the development of tendon ruptures. This
      study aims to characterize the factors involved in patients with renal disease
      and simultaneous bilateral quadriceps tendon rupture. METHODS: All reported cases
      of simultaneous bilateral quadriceps tendon rupture were identified using
      MEDLINE. Each case was reviewed for information regarding this injury. RESULTS:
      Of the 65 cases reviewed, 24 cases involved patients with renal disease. Males
      were more often affected than females, almost a 2 : 1 ratio. The mean age of
      injury was 36 years. Most patients (63%) had signs of secondary
      hyperparathyroidism. The average length of renal disease was 13 years while the
      average length on dialysis was 6.5 years. Age, gender, mechanism of injury, time
      before diagnosis, location of rupture, method of repair, presence of
      hyperparathyroidism, length of renal disease or length on dialysis were not
      related to functional outcome. However, length on dialysis was related to
      mechanism of injury. CONCLUSIONS: Most patients with renal disease and
      simultaneous bilateral quadriceps tendon rupture have good functional recovery.
      Duration of dialysis is related to spontaneous tendon rupture and should be
      considered a complication of chronic renal failure.

PMID- 12227681
TI  - Oxidative stress and TGFbeta in kidney-transplanted patients with cyclosporin
      induced hypertension. Effect of carvedilol and nifedipine.
AB  - Cyclosporin is a powerful stimulator of oxidative stress signaling, leading to
      TGFbeta production, NO degradation, endothelial dysfunction, hypertension and
      post-transplant nephropathy. Carvedilol, alpha1-beta-blocker with strong
      antioxidant activity, may interfere with this chain of events. Therefore, we
      measured monocyte ecNOS, TGFbeta and heme oxygenase-1 (HO-1) mRNA level and
      plasma nitrite/nitrate, 3-nitrotyrosine, an estimate of peroxynitrite, and total
      plasma antioxidant power in kidney-transplanted patients with post-transplant
      hypertension, before and after treatment with carvedilol, 25 - 50 mg o.d. orally
      for 4 months (n = 15). The dihydropyridine calcium channel blocker nifedipine (n
      = 10) was used as comparator antihypertensive drug. Blood pressure fell to a
      similar extent with both drugs. Carvedilol increased plasma antioxidant power and
      HO-1 mRNA and reduced 3-nitrotyrosine and TGFbeta mRNA levels, while the same was
      not observed with nifedipine. Monocyte ec NOS mRNA levels and plasma
      nitrite/nitrate were higher in the patients than in a normotensive healthy
      control group and were unaffected by either treatment. In conclusion, carvedilol
      reduces the oxidative stress and corrects the altered cellular signaling mediated
      by oxidative stress in CsA-induced post-transplant hypertension. Therefore, it
      may prevent long-term complications, such as endothelial dysfunction,
      fibrogenesis and post-transplant nephropathy by decreasing NO degradation and
      production of TGFbeta, a key fibrogenic cytokine, and by activating HO-1
      production.

PMID- 12227684
TI  - Utility of ultrasonographic venous assessment prior to forearm arteriovenous
      fistula creation.
AB  - AIM: The purpose of this study was to evaluate the clinical utility of Doppler
      ultrasound (US) prior to native forearm arteriovenous fistula (AVF) creation.
      MATERIALS AND METHODS: US mapping was carried out pre-operatively to evaluate the
      major veins and arteries in the appropriate arm. One hundred and 6 patients were
      identified retrospectively over 2 years with complete clinical and US data. A
      failed fistula was defined as an inability to provide blood flow to meet adequacy
      targets by 6 months (urea reduction ratio > or = 65%). RESULTS: Twenty-nine
      patients (27.4%) had successful forearm AVFs. The mean minimum forearm cephalic
      vein diameter (CVD) was 2.51 +/- 0.14 and 2.23 +/- 0.06 mm in successful and
      failed fistulae, respectively (p = 0.04). This result was primarily due to
      differences observed in women. A receiver operator curve analysis showed that a
      cutpoint of 2.6 mm for minimum forearm CVD had the greatest predictive value with
      a likelihood ratio of 3.94 (95% CI: 1.97 - 7.84) for fistula failure.
      Multivariate logistic regression analysis determined that male gender and minimum
      forearm CVD were the only significant predictors for fistula success with odds
      ratios of 3.90 (95% CI: 1.30 - 11.68) and 2.31 (95% CI: 1.00 - 5.43),
      respectively. The study is limited by the possibility that US results in patients
      may have lead to an alternative type of access being attempted. CONCLUSIONS: US
      mapping prior to forearm AVF creation is of modest benefit. Only male gender and
      minimum forearm CVD were predictive of AVF success.

PMID- 12227685
TI  - Use of the Tesio catheter for hemodialysis in patients with end-stage renal
      failure: a 2-year prospective study.
AB  - BACKGROUND: The Tesio catheter system has been proposed to be a reliable source
      of vascular access for the dialysis patient with low rates of infection and other
      complications. Whether such catheters provide reliable short- and long-term
      access remains undetermined. METHODS: This study prospectively examined all Tesio
      lines inserted over a 2-year period in patients with end-stage failure with
      careful recording of all catheter complications and reasons for catheter loss.
      RESULTS: 100 catheters were inserted in 82 patients giving a total experience of
      13,749 catheter days; 74 catheters were inserted into the jugular veins, the
      remainder into the femoral veins; 82 insertions were covered with antibiotics. At
      the end of the study, 29 catheters remained in situ. Of the remaining 71
      catheters, 27 catheters were removed because of fashioning of definitive access.
      Nine catheters were lost due to infection and 10 were lost due to non-function;
      19 patients died with a functioning catheter. Episodes ofnon-function were the
      major complications, although catheter patency was restored in 90% of cases
      utilizing urokinase and warfarin. Overall 80% of femoral and 16% of jugular
      catheters required anticoagulation. CONCLUSIONS: Tesio catheters inserted into
      the jugular or femoral veins can provide excellent access whilst awaiting
      definitive dialysis access. They are well-tolerated with a low complication rate
      compared to standard temporary central venous catheters. Non-function remains a
      significant problem, especially in femoral catheters, which should be
      anticoagulated following insertion. Because of our results we suggest that these
      catheters be used as part of the co-ordinated approach to the management of
      vascular access in end-stage renal failure patients without definitive access.

PMID- 12227686
TI  - Impact of iron dextran on polymorphonuclear cell function among hemodialysis
      patients.
AB  - BACKGROUND: Polymorphonuclear cell (PMN) dysfunction and the increased use of
      parenteral iron may be important contributory factors to bacterial infections
      among patients with end-stage renal disease (ESRD) on maintenance hemodialysis
      (HD). We compared the in vitro impact of a commonly used parenteral iron
      preparation, iron dextran, on PMN function and viability between a group of HD
      patients with normal iron indices and healthy subjects. METHODS: Eleven patients
      with ESRD on HD and 10 healthy subjects were studied. PMN harvested from
      heparinized blood were incubated with iron dextran (0 - 20 mM) in culture medium
      (RPMI) for 24 hours at 37 degrees C with 5% CO2 following which function and
      viability were assessed by flow cytometry using appropriate fluorescent labels.
      RESULTS: Unstimulated, S. aureus and N-formyl-methionyl-leucyl-phenylalanine
      (fMLP)-stimulated hydrogen peroxide (H2O2) production was significantly higher in
      PMN unexposed to iron dextran from HD patients compared to those from healthy
      subjects. Iron dextran had no impact on unstimulated PMN H2O2 production in
      either group. In the healthy group, the only significant change occurred with 4
      beta-phorbol 12-beta-myristate 13-alpha-acetate (PMA) stimulation, where cells
      exposed to 0.2 and 2.0 mM iron dextran produced less H2O2 relative to PMN
      unexposed to iron dextran (p < 0.05). In the HD group, all concentrations of iron
      dextran significantly attenuated H2O2 production stimulated by S. aureus, fMLP
      and PMA compared to PMN unexposed to iron dextran. Although PMN phagocytosis
      decreased with exposure to increasing concentration of iron dextran in both
      healthy subjects and HD patients, these changes did not achieve statistical
      significance. No significant changes in PMN viability or apoptosis were seen in
      either group after exposure to iron dextran. CONCLUSIONS: These results indicate
      that iron dextran, a standard parenteral iron preparation, attenuates PMN
      function in HD patients with normal iron indices at clinically relevant
      concentrations. Further studies are required to evaluate and compare the impact
      of newer preparations of parenteral iron, such as iron sucrose and ferric
      gluconate, on PMN function.

PMID- 12227687
TI  - Natural history of acute HCV infection in hemodialysis patients.
AB  - AIMS: Chronic liver disease develops in the majority of non-uremic patients with
      hepatitis C virus (HCV) infection. The aim of this study was to analyze the
      evolution towards chronic hepatopathy in 19 cases of acute hepatitis C observed
      in hemodialysis patients from 1990 to 2001. METHODS: A prospective follow-up
      study on HCV infection was conducted in 3 HD units from April 1990 to June 2001
      to study clinical outcomes after acute hepatitis C. A total of 781 patients were
      tested monthly for alanine aminotransferase and anti-HCV in serum. In this
      period, 19 patients suffered from acute hepatitis C. Evolution to chronic liver
      disease in the follow-up was evaluated by means of biochemical (increased ALT)
      and virological criteria (HCV-RNA+). The transmission mechanism, the apparition
      of anti-HCV, clinical manifestations and mortality were also investigated.
      RESULTS: In 15 (78.9%) of the 19 patients, the viremia remained positive (chronic
      viremia) and 11 patients (57.8%) evolved to chronic liver disease (chronic
      viremia and high transaminase levels) with a median follow-up of 3 years (range 1
      - 6). Five of them who underwent liver biopsies had histologic signs of chronic
      active hepatitis. One of them (5.2%) evolved to liver cirrhosis in the follow-up.
      In 4 out of 19 patients (21%) the HCV infection resolved. Although 7 (36.8%) of
      them died in the follow-up, acute hepatitis C infection was not a short-term
      independent risk factor of death. CONCLUSIONS: Three years after acute hepatitis
      C, 87.5% of the hemodialysis patients remained HCV-RNA positive and 56.2% evolved
      to chronic liver disease. It is important to stress that HCV infection
      spontaneously cleared in 4 out of 19 patients (21%).

PMID- 12227688
TI  - Acute interstitial nephritis secondary to infectious mononucleosis.
AB  - Renal involvement in infectious mononucleosis (IM) is infrequent. In most cases
      it is self-limited and is rarely associated with loss of renal function. The
      purpose of this case report is to document a case of acute interstitial nephritis
      (AIN) leading to acute renal failure (ARF) in a patient with Epstein-Barr virus
      (EBV) infection and to review literature of EBV infection and its renal
      manifestation. The patient was managed with hemodialysis and steroids and made an
      uneventful recovery. Renal involvement in IM may be more common than generally
      appreciated and may occasionally lead to ARF. Therapy with corticosteroids may
      have role in the management of IM-induced ARF and may shorten the duration of
      renal failure.

PMID- 12227689
TI  - Oral doxercalciferol therapy for secondary hyperparathyroidism in a peritoneal
      dialysis patient.
AB  - Control of hyperphosphatemia and the administration of vitamin D are the primary
      treatment modalities for the prevention and management of secondary
      hyperparathyroidism. Vitamin D therapy for secondary hyperparathyroidism has been
      limited by the development of hypercalcemia and/or hyperphosphatemia due to
      increased intestinal absorption of these minerals. Recently, selective vitamin D
      analogs specifically designed to suppress parathyroid hormone (PTH) without
      causing hypercalcemia or hyperphosphatemia have shown promise for the treatment
      of secondary hyperparathyroidism in uremia. This case report describes the
      successful use of doxercalciferol to treat severe secondary hyperparathyroidism
      in an adult male patient undergoing chronic peritoneal dialysis, with a follow-up
      period of 9 months. During this period, the patient's hyperparathyroidism was
      rapidly and easily controlled. Treatment was complicated by a single incident of
      over suppression of PTH, with concomitant hypercalcemia. This quickly resolved
      upon temporary discontinuation of doxercalciferol therapy, after which therapy
      was resumed without further incident.

PMID- 12227691
TI  - A benign outcome of nephritis despite C-ANCA/PR3 positivity.

PMID- 12227690
TI  - A case of lupus nephritis with alteration of the glomerular basement membrane
      associated with Takayasu's arteritis.
AB  - A 47-year-old Japanese woman with both Takayasu's arteritis (TA) and systemic
      lupus erythematosus (SLE) presented with unequal pulses in the upper extremities,
      diarrhea and proteinuria. In 1986, when she was 38 years old, angiography
      revealed stenosis of the left subclavian artery. In 1994, SLE was diagnosed on
      the basis of clinical and laboratory findings, including renal dysfunction,
      hematologic and immunologic abnormalities, a high titer of antinuclear antibody
      and a positive lupus band test on the skin. Renal biopsy showed lupus nephritis
      and glomerular lesions with a bubble-like appearance of the glomerular capillary
      wall with TA. Lupus nephritis coexisting with glomerulonephropathy associated
      with TA has rarely been reported.

PMID- 12227692
TI  - Valacyclovir neurotoxicity in a patient with end-stage renal disease treated with
      continuous ambulatory peritoneal dialysis.

PMID- 12227693
TI  - Factors associated with progression of IgA nephropathy are related to renal
      function--a model for estimating risk of progression in mild disease.
AB  - BACKGROUND: A number of factors are linked to the outcome of IgA nephropathy
      (IgAN). However, it has been difficult to compare results of studies since
      patient populations have varied greatly. There were 3 aims in the study reported
      here, namely to compare factors associated with renal outcome in IgAN patients
      with different levels of renal function on diagnosis; to determine factors which
      were independently associated with progression of renal disease in initially mild
      IgAN; and to create a model for the estimation of the risk of progression in
      individual IgAN patients with normal renal function on diagnosis. METHODS: Two
      hundred and fifty-nine IgAN patients who had been followed on average for 9.1 (SD
      4.5) after diagnosis were divided into 2 groups on the basis of renal function on
      diagnosis. In group 1 (98 patients), Ccr (creatinine clearance, estimated by the
      Cockcroft-Gault formula) was < 85 ml/min, in group 2 (161 patients) > or = 85
      ml/min. Univariate analyses were used to find significant differences between
      progressors and non-progressors in both groups. Logistic regression analysis was
      used to determine factors independently associated with progression in group 2.
      RESULTS: Several factors were found to be associated with outcome in both groups,
      such as hypertension, level of Ccr, serum cholesterol, proteinuria, and also
      histopathological changes. Factors associated with progression in patients with
      initially decreased renal function (group 1), were predictable, such as male sex,
      absence of episodes of macroscopic hematuria, serum urate level and degree of
      tubular atrophy. Surprisingly, in patients with initially normal renal function
      (group 2), numbers of urinary erythrocytes were associated with outcome. The
      factors independently associated with progression in this group were number of
      urinary erythrocytes, existence of hypertension and in histopathology
      arteriolosclerosis and the level of glomerular score. A model for estimating risk
      of progression on the basis of various combinations of factors found to be
      independently associated with outcome is presented. CONCLUSIONS: We concluded
      that association between variable and outcome in IgAN depends partly on renal
      function at the time of assessment of the factor. Since there are factors which
      are independently associated with the outcome of early and apparently mild
      disease, early diagnosis of IgAN is desirable: outcome in mild IgAN can be
      predicted reliably on the basis of factors found to be independently associated
      with outcome.

PMID- 12227694
TI  - Nephropathy of cyanotic congenital heart disease: clinical characteristics and
      effectiveness of an angiotensin-converting enzyme inhibitor.
AB  - AIMS: Nephropathy has long been recognized as a potential complication of
      cyanotic congenital heart disease (CCHD). There have been few large-scale studies
      or clinical reports on renal impairment in patients with CCHD; similarly, very
      few studies have examined the drug treatment of nephropathy in CCHD. We examined
      the clinical characteristics and effectiveness of enalapril, an angiotensin
      converting enzyme inhibitor (ACE-I), in patients with CCHD complicated with
      significant proteinuria. MATERIALS AND METHODS: The clinical records of 37
      patients with CCHD were evaluated; all were older than 10 years of age (median
      19, range from 10 to 27) and had regular check-ups, including urinalysis. The
      treatment criteria for enalapril administration included significant proteinuria
      (urinary excretion > 1.0 g/24 h), stable cardiac condition and blood pressure
      within the normal range. RESULTS: Eleven patients (29.7%) had persistent
      proteinuria, 6 patients met the enalapril treatment criteria and 5 patients were
      treated for more than 12 months. Enalapril apparently reduced the urinary protein
      excretion in 4 of the 5 patients (80%). No consistent improvement of renal
      function, as evidenced in the glomerular filtration rate (GFR), renal plasma flow
      (RPF) or filtration fraction (FF) was found in these patients, but neither were
      any significant adverse effects noted. CONCLUSION: The incidence of nephropathy
      among patients with CCHD was about 30%, which was consistent with previous
      studies. It is worth considering the use of ACE-I when nephropathy accompanies
      CCHD.

PMID- 12227695
TI  - Oxidative stress correlates with left ventricular volume after acute myocardial
      infarction.
AB  - It has been suggested that oxidative stress may play a role in the
      pathophysiology of heart failure. However, little is known about the clinical
      relationship between oxidative stress and left ventricular dilatation after acute
      myocardial infarction (AMI). We prospectively studied 28 consecutive patients,
      successfully treated with primary coronary angioplasty, after their first AMI. To
      evaluate oxidative stress, plasma oxidized low-density LDL levels (U/mL) were
      measured serially 1 day, 7 days, 14 days, 30 days, and 90 days after the onset of
      AMI using a specific sandwich enzyme-linked immunosorbent assay. Left
      ventriculography and coronary angiography were obtained in all patients 3 months
      after the AMI and infarct-related arteries were all patent. Peak plasma oxidized
      LDL levels were seen 7 days after AMI (after 1 day: 14.7+/-1.5, 7 days: 21.0+/
      2.8, 14 days: 20.2+/-2.8, 30 days: 18.3+/-2.5, 90 days: 16.5+/-2.3 U/mL). Plasma
      oxidized LDL levels 7 days after AMI were significantly correlated with left
      ventricular end-diastolic volume (115+/-7 mL; r=0.54, P=0.0025) and end-systolic
      volume (58+/-5 mL; r=0.49, P=0.008) 3 months after the AMI. Moreover, they were
      also correlated with end-diastolic volume index (68+/-4 mL/m2, r=0.40, P<0.05).
      However, no correlation was seen between peak plasma oxidized LDL levels and
      ejection fraction. These findings suggest that oxidative stress may play an
      important role in the development and progression of left ventricular remodeling
      after AMI.

PMID- 12227696
TI  - Development of C-reactive protein and fibronectin levels in coronary surgery
      patients: a comparison of on-pump, off-pump sternotomy and off-pump left anterior
      small thoracotomy groups.
AB  - In this prospective study, we monitored two laboratory parameters, C-reactive
      protein (CRP) and fibronectin (FIN) levels, in 30 patients undergoing elective
      surgery for ischemic heart disease. These patients were divided into three groups
      according to the surgical procedure used: group A, approach through a median
      sternotomy with the use of extracorporeal circulation; group B, approach through
      a median sternotomy without the use of extracorporeal circulation; and group C,
      approach through a left anterior small thoracotomy (LAST) without the use of
      extracorporeal circulation. Peak CRP levels were found in all three groups on the
      second postoperative day, with the mean levels being statistically significantly
      higher in group C. This group also showed the highest mean CRP levels on the
      third and fourth postoperative days, with the difference being statistically
      nonsignificant. These findings can be explained by an enhanced production of
      cytokines, which in turn trigger CRP synthesis, induced by postoperative pain due
      to the LAST procedure. No statistically significant correlation between
      preoperative CRP levels and their postoperative development was found. None of
      the groups studied showed any statistically significant decrease in FIN plasma
      levels, either prior to adjustment for hemodilution or after adjustment for
      hematocrit and serum albumin.

PMID- 12227697
TI  - Color Doppler tissue imaging in assessing the elastic properties of the aorta and
      in predicting coronary artery disease.
AB  - We hypothesized that the change in aortic elastic properties could directly be
      shown with color Doppler tissue imaging (CDTI), that these findings could be
      related to aortic stiffness and distensibility and that, through these, coronary
      artery disease (CAD) could be predicted. One hundred and twenty six patients
      (group I: 83 with CAD, mean age 54+/-10 years, 18 female, 65 male; group II: 43
      without CAD, mean age 53+/-10 years, 27 female, 16 male) having been evaluated
      for coronary artery disease by angiography were examined by echocardiography.
      Arterial pressure was measured immediately before echocardiographic evaluation.
      Internal aortic systolic and diastolic diameters by M-mode echocardiography and
      aortic upper wall tissue velocities (Aortic S, E, A, m/sec) by CDTI were measured
      3 cm above the aortic valve. Lateral mitral annulus tissue velocities (Annulus S,
      E, A, m/sec) were also recorded. Aortic distensibility (cm2 x dynes(-1)) and
      aortic stiffness index were calculated using formulas. In the statistical
      analyses, CAD risk factors and left ventricular ejection fraction were used for
      adjustment. Aortic stiffness (2.79+/-3.49 vs 1.62+/-1.31, P=0.03), distensibility
      (1.55+/-1.46 vs 2.37+/-3.08, P=0.04), and aortic S velocity (0.057+/-0.016 vs
      0.064+/-0.015, P=0.02) differed significantly between groups I and II. After
      adjustment, while aortic stiffness and S velocity were still statistically
      different (P=0.04; P=0.03 respectively), the significance of the difference in
      aortic distensibility disappeared (P=0.051). Aortic stiffness and aortic S
      velocity (0.06 m/sec<) were important CAD determinants (Odds ratio=1.4 P=0.03;
      Odds ratio=3.6 P=0.01, respectively), but aortic distensibility was not. Aortic
      stiffness was correlated only with aortic S velocity (r=-0.28, P=0.01), and
      aortic distensibility had a significantly positive correlation with aortic S
      velocity (r=0.20, P=0.02). The interobserver and intraobserver correlation
      coefficients for aortic S velocities were 0.65 and 0.71, respectively (P<0.05).
      Elastic properties of the aorta can directly be assessed by reproducibly
      measuring the movements in the upper wall of the aorta by CDTI. Reduced aortic S
      velocity is associated with increased aortic stiffness. Increased aortic
      stiffness and reduced aortic S velocity are important predictors of CAD.

PMID- 12227698
TI  - Atrial electrophysiological properties evaluated by right and left atrial pacing
      in patients with or without atrial fibrillation.
AB  - Coronary sinus (CS) pacing has been shown to prevent induction of atrial
      fibrillation (AF) by suppression of the propensity of atrial premature beats at
      high right atrium (HRA) to induce local conduction delay at the posterior
      triangle of Koch. However, other mechanisms of CS pacing in preventing induction
      of AF have not been explored. This study investigated whether a differential
      conduction delay exists between the HRA and distal CS pacing in patients with
      paroxysmal AF but not in patients without AF. Nine patients with atrioventricular
      reentrant tachycardia utilizing a left accessory pathway undergoing catheter
      ablation were included in this study. Group 1 consisted of 5 patients with
      clinically documented paroxysmal AF and group 2 4 patients without a history of
      AF. The effective refractory periods (ERPs) of HRA, distal CS, and four different
      left atrial sites were determined. The interatrial conduction time and conduction
      delay between the HRA and distal CS during HRA or distal CS pacing were measured.
      The interatrial conduction delay (ICD) from the HRA to the distal CS during HRA
      pacing was significantly longer than that from the distal CS to the HRA during
      distal CS pacing in patients of group 1. However, the ICD from the HRA to the
      distal CS during HRA pacing was not significantly longer than that from the
      distal CS to the HRA during distal CS pacing in group 2 patients. A differential
      conduction delay between the HRA and the distal CS pacing is present in this
      specific population of patients with paroxysmal AF but not in patients without
      AF. The shorter conduction delay during DCS pacing may contribute to the
      prevention of induction of AF.

PMID- 12227699
TI  - Left atrial maximum volume is a recurrence predictor in lone atrial fibrillation:
      an acoustic quantification study.
AB  - Predictors of recurrence in lone atrial fibrillation have not been clearly
      identified. Acoustic quantification (AQ) is a promising method in the assessment
      of left atrial (LA) volumes. The purpose of the present study was to investigate
      the potential of LA volumes obtained by standard manual tracing and AQ methods in
      predicting AF-recurrence after restoring the sinus rhythm in patients with lone
      AF, and to test the agreement between the two approaches. Standard
      echocardiography combined with AQ was performed in 28 patients with lone AF one
      hour after the sinus rhythm was regained, and in 10 controls. LA volumes were
      determined by conventional manual tracing and AQ methods. AQ waveforms of LA were
      obtained by drawing a region of interest around the LA border. The agreement of
      the two methods was tested by Bland-Altman analysis. Patients were followed up
      for 6 months for the occurrence of AF recurrence. A good correlation was observed
      between AQ and manual tracing methods in determining both minimal (r=0.59) and
      maximal (r=0.88) LA volumes. Patients with AF recurrence had a significantly
      larger maximum LA volume as assessed with both methods (P<0.05 for both). M-mode
      derived LA dimension and isovolumic relaxation time were additional predictors of
      recurrence in patients with lone AF. In lone AF, patients prone to recurrence
      could be predicted by determining LA maximum volume assessed either by AQ or
      manual tracing methods. AQ provides on-line, accurate estimation of LA volumes.

PMID- 12227700
TI  - Left ventricular diastolic dysfunction induced by cyclophosphamide in blood stem
      cell transplantation.
AB  - Cardiac complications are major limiting factors regarding the success of high
      dose chemotherapy supported by blood stem cell transplantation (BSCT). The
      cardiotoxicity of cyclophosphamide remains obscure relative to that of
      anthracyclines. The aim of this study was to estimate noninvasively the
      cardiotoxicity of cyclophosphamide administered during the pretransplant
      conditioning of BSCT for patients with various hematological diseases. A total of
      27 consecutive patients were divided into two groups depending on the
      conditioning regimen, ie, group A (n=15) which received cyclophosphamide (median
      dose of 120 mg/kg; range 100 to 200 mg/kg) and group B (n=12) which did not.
      Ultrasound cardiograms (UCG) and signal-averaged electrocardiograms (SAECG) were
      recorded in the two groups both preceding and following the BSCT. There were no
      statistical intergroup or intragroup differences in left ventricular (LV)
      dimensions or contractile function. Significant (P<0.01) posttransplant increases
      in interventricular septal wall thickness and Ap/Ep ratio were noted in group A.
      Moreover, the filtered QRS duration as estimated by SAECG was prolonged (P<0.05)
      whereas the summated LV voltage (S(V1)+R(V5)) was reduced in the posttransplant
      period only in group A. These results suggest that early cyclophosphamide
      cardiotoxicity was characterized by LV diastolic rather than systolic
      dysfunction. These findings may contribute to acute hemodynamic deterioration
      observed after cyclophosphamide-containing conditioning chemotherapy.

PMID- 12227701
TI  - Surgical treatment of malignant tumors of the right heart.
AB  - Seven patients with malignant cardiac tumors were treated surgically in the
      Department of Cardiothoracic Surgery of the University of Tokyo between 1981 and
      2000. Their treatments and outcomes are summarized and discussed. The ages of the
      patients ranged from 21 to 70 years old (mean: 49.5+/-15) and there were three
      males and four females. The histopathological diagnoses were hepatocellular
      carcinoma (HCC), spindle cell sarcoma, round cell sarcoma, osteosarcoma, renal
      cell carcinoma, and leiomyosarcoma. In four of the cases, the tumor extended or
      metastasized from other organs, while in the other three cases it originated in
      the heart. Before the cardiac operation, an above-knee amputation, left
      nephrectomy, transarterial embolization, or extended right hepatic lobectomy had
      been performed to treat the primary site of the tumor. Tumor resection using
      cardiopulmonary bypass was performed in every case. The NYHA classification of
      heart failure was significantly improved (preop: 3.3+/-0.8, postop: 1.9+/-0.7
      [P<0.001]). The mean survival period of the patients who died was 8.8+/-7.0
      months. A patient with renal cell carcinoma is still alive after 87 months of
      follow-up. In summary, surgical treatment of malignant tumors of the right heart
      can improve the QOL in patients with cardiac failure. However, its effectiveness
      was temporary in all cases except one case of renal cell carcinoma.

PMID- 12227702
TI  - Decreased expression of Na+/H+ exchanger isoform 1 (NHE1) in non-infarcted
      myocardium after acute myocardial infarction.
AB  - Although cardiac NHE1 is activated during myocardial ischemia and reperfusion
      injury, little is known about changes in expression in non-infarcted myocardium
      after acute myocardial infarction (AMI). The purpose of this study was to examine
      left ventricular function and region dependent NHE1 expression after myocardial
      infarction. Therefore, we produced two AMI models in rats, a small infarction
      model which was continuously ligated at the branches of the left coronary artery,
      and an extensive infarction model continuously ligated at the root of the artery.
      We examined NHE1 mRNA expression using RNase protection assay and protein levels
      using Western blot analysis in non-infarcted myocardium during the 24 hour period
      after AMI. The level of NHE1 mRNA and protein expression in the whole heart
      including the infarcted myocardium did not change after a small infarction. On
      the other hand, in the case of an extensive infarction, the levels of NHE1 mRNA
      and protein expression decreased significantly by 21.5% (P<0.05) and by 22.0%
      (P<0.05), respectively, in non-infarcted myocardium. Left ventricular systolic
      pressure (LVSP) decreased significantly by 13% and 38% with the branch and root
      ligation, respectively. However, left ventricular end-diastolic pressure (LVEDP)
      only increased with the root ligation. These results indicate that NHE1
      expression decreased in response to extensive myocardial infarction only in non
      infarcted myocardium. The present study may be important in furthering the
      understanding of NHE1 in myocardial infarction and suggests that decreased
      expression of NHE1 in non-infarcted myocardium may decrease the extent of cardiac
      cell injury.

PMID- 12227703
TI  - Idiopathic ventricular fibrillation in a patient with Wolff-Parkinson-White
      syndrome.
AB  - Ventricular fibrillation in a patient with ventricular preexcitation is usually
      due to atrial fibrillation with an extremely rapid ventricular rate from which it
      degenerates. We present a case with Wolff-Parkinson-White syndrome and coexistent
      idiopathic ventricular fibrillation. The patient, a 23-year-old male, had had a
      cardiac arrest four years earlier. In electrophysiological study, the accessory
      pathway was located in the left posteroseptal region and successfully eliminated
      with radiofrequency catheter ablation. After the ablation procedure, ventricular
      fibrillation was induced with programmed ventricular stimulation. A dual chamber
      implantable cardioverter defibrillator was implanted in the patient.

PMID- 12227704
TI  - A subacute left ventricular free wall rupture after thrombolytic and glycoprotein
      IIb/IIIa inhibitor treatment: an overlooked finding of left ventriculography.
AB  - Subacute left ventricular free wall rupture is a rare complication in acute
      myocardial infarction. With the increasing use of thrombolytic agents and
      glycoprotein IIb/IIIa inhibitors, this complication has been increasing recently.
      We report a case of subacute cardiac rupture with frank pericardial effusion
      receiving thrombolytic and glycoprotein IIb/IIIa inhibitor therapies.

PMID- 12227705
TI  - Nonsurgical percutaneous retrieval of dislodged Port-A catheters from pulmonary
      artery in children.
AB  - A total of 110 central venous access procedures using Port-A catheters were
      performed in our center for pediatric patients with oncologic or hematologic
      diseases over a period of 6 years from November 1994 to June 2000. Spontaneous
      dislodgement of the outlet catheters was noted in two cases. Both dislodged
      catheters were located in the left pulmonary artery and were successfully
      retrieved via the right femoral vein by nonsurgical transvenous snares. Awareness
      of the possibility of spontaneous catheter dislodgement and embolization of Port
      A catheters is important as prompt retrieval will prevent further serious
      complications. When the procedure is performed by an open surgical method, to
      reduce the possibility of spontaneous catheter dislodgement, the use of a
      guidewire is recommended while a Port-A catheter is being inserted into the
      subclavian vein.

PMID- 12227706
TI  - Unusual petal-like fibromuscular dysplasia as a cause of acute abdomen and
      circulatory shock.
AB  - Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory segmental
      arterial occlusive disorder that involves primarily the renal and carotid
      arteries, and less often the coronary, iliac, and visceral arteries. We report
      the case of 78-year-old Japanese woman who presented with acute abdomen
      complicated by shock. Autopsy revealed hemorrhagic necrosis of the small
      intestine due to severe narrowing of the mesenteric arteries. Histologically,
      smooth muscles showed in-bundle hyperplasia surrounding the adventitia together
      with medial and perimedial fibrodysplasia of these arteries, forming the
      characteristic petal-like appearance of FMD. No occlusive thrombus was observed.
      Further, another medial fibrodysplasia type of FMD was also seen in the renal and
      left circumflex coronary arteries. Unusual proliferation of smooth muscles
      resulted in the petal-like atypical FMD at the superior mesenteric artery.

PMID- 12227707
TI  - New protocol to detect coronary spastic angina without fixed stenosis.
AB  - A new combined test, accelerated exercise following mild hyperventilation (HV),
      was examined to determine whether it is effective at detecting a positive
      response in patients with pharmacologically-induced coronary vasospasm and near
      normal coronary arteries. Fifty-eight consecutive patients who underwent both
      triple non-invasive spasm provocation tests and diagnostic coronary angiography
      were enrolled. They all had pharmacologically-induced coronary vasospasms and no
      significant organic stenosis. In these patients, an HV test was performed first,
      followed by a treadmill exercise test (TET), and finally the new combined test
      under no medication within 3 days. Of the 58 patients, positive responses were
      observed in 9 patients to the HV, in 15 to the TET, and in 35 to the newly
      combined test. The remaining 21 patients had negative responses although the
      triple sequential tests were perfomed. Thus, the sensitivities of the HV test,
      TET, and newly combined test were 16% (9/58), 26% (15/58), and 63% (35/56),
      respectively. Forty-six subjects with near normal coronary arteries and no ACh
      provoked spasm served as controls. None of these subjects had positive responses
      to any of these three tests, and thus their specificity was all 100%. No serious
      or irreversible complications were seen in this study. We recommend this newly
      combined protocol for the induction of coronary artery spasm in patients with
      vasospastic angina pectoris and without significant stenosis as a diagnostic
      tool.

PMID- 12227708
TI  - Angioscopic evaluation of stabilizing effects of an antilipemic agent,
      bezafibrate, on coronary plaques in patients with coronary artery disease: a
      multicenter prospective study.
AB  - To evaluate the stabilizing effects of an antilipemic agent, bezafibrate, on
      coronary plaques, we carried out a prospective angioscopic and angiographic open
      trial. From April 1997 to December 1998, 24 patients underwent coronary
      angioscopy of plaques in non-targeted vessels during coronary interventions and
      then again 6 months later. The patients were divided into control (10 patients,
      14 plaques) and bezafibrate (14 patients, 21 plaques) groups. Oral administration
      of bezafibrate (400 mg/day) was started immediately after the intervention and
      was continued for 6 months. The vulnerability score was determined based on the
      angioscopic characteristics of plaques and compared before and 6 months later.
      Six months later, the vulnerability score was reduced (from 1.6 to 0.8; P<0.05)
      in the bezafibrate group and unchanged (from 1.4 to 1.3; NS) in the control
      group. In the bezafibrate group, the changes in the vulnerability score were not
      correlated with those in % stenosis or minimal lumen diameter. The plasma total
      cholesterol level (T-C) was unchanged, triglyceride level (TG) was decreased, and
      high density lipoprotein cholesterol level (HDL-C) was increased in the
      bezafibrate group, but were unchanged in the control group. In the bezafibrate
      group, T-C and TG were decreased and HDL-C was increased in patients with a
      reduced vulnerability score but were unchanged in those with an unchanged score.
      These results indicate that 6 month administration of bezafibrate stabilizes
      coronary plaques and that the stabilization is not correlated with angiographic
      changes.

PMID- 12227709
TI  - Effects of anti-vasospastic agents in Japanese patients with dilated
      cardiomyopathy and coronary vasospasm.
AB  - The pathogenesis of dilated cardiomyopathy (DCM) is unknown, but clinical
      evidence suggests that coronary vasospasm is associated with the development of
      DCM in some cases. In the present study, we aimed to clarify the prevalence of
      coronary vasospasm in patients with DCM, the characteristics of patients with DCM
      and coronary vasospasm, and the effects of anti-vasospastic agents on patients
      with DCM and coronary vasospasm. This study included 18 consecutive patients with
      DCM who underwent cardiac catheterization with ergonovine provocation testing.
      The patient was diagnosed as having coronary vasospasm if ergonovine induced
      coronary vasoconstriction > or = 75% diameter narrowing was observed compared to
      the diameter after nitroglycerin administration. Six (33%) patients were found to
      have coronary vasospasm and anti-vasospastic agents were added after the cardiac
      catheterization. The prevalence of atrial fibrillation in the patients with DCM
      and coronary vasospasm was greater than that in DCM without coronary vasospasm
      [67% vs 8% (P<0.05)]. The left ventricular end-diastolic dimension decreased from
      61 mm (56/64) to 55 mm (53/56) (median, 25th/75th percentile, P<0.05) and the
      left ventricular ejection fraction increased from 36% (32/40) to 47% (46/48)
      (median, 25th/ 75th percentile, P<0.05) after the administration of anti
      vasospastic agents and 4 of the 6 patients improved symptomatically. Therefore,
      ergonovine provocation testing is useful in identifying patients with DCM and
      coronary vasospasm, in whom cardiac performance is expected to be improved with
      anti-vasospastic agent therapy. DCM patients with atrial fibrillation may be a
      clue for identifying patients with coronary vasospasm.

PMID- 12227710
TI  - Coronary artery bypass grafting in patients with poor left ventricular function.
AB  - Coronary artery bypass grafting (CABG) in patients with poor left ventricular
      function remains a surgical challenge and is still controversial. The purposes of
      this study were to evaluate the effectiveness of CABG in such patients when
      performed without case selection on the basis of preoperative viability tests and
      to determine the predictors of postperative outcome. The preoperative,
      perioperative, and postoperative early and mid-term follow-up data of 273
      patients with < or = 30% left ventricular ejection fraction (LVEF) who underwent
      isolated CABG between January 1995 and November 2000 were evaluated. Preoperative
      echocardiography and cardiac catheterization, and postoperative control
      echocardiography were performed in all patients. Follow-up was achieved via
      monthly periodical examinations in the first 6 months, and thereafter by either
      regular visits or phone contact. Preoperatively, 242 (88.65%) patients were in
      NYHA class III or IV, and the mean LVEF was 26.51 +/- 3.64%. The overall hospital
      mortality total was 14 (5.13%) patients. There were 44 (16.12%) late mortalities.
      Postoperative morbidities were observed in 74 (27.1%) patients. Two-hundred and
      two (93.95%) of the surviving 215 (78.75%) patients were in NYHA class I or II at
      49.55 +/- 14.84 months of follow-up. Postoperative follow-up echocardiographic
      examinations revealed a mean LVEF of 39.66% +/- 5.43%. The improvements in
      functional capacity and LVEF were significant. Advanced age, diabetes,
      hypertension, cross-clamp time >60 min, bypass time>120 min, and severity of
      functional class (class III-IV of NYHA) were found to be the determinants of
      mortality. However, multivariate analyses revealed only older age and class III
      IV of NYHA and CCS were predictors of mortality. The low mortality and morbidity
      rates as well as satisfactory postoperative improvements in functional capacity
      and LVEF measurements support the use of CABG without the need for any viability
      assessment in patients with left ventricular dysfunction.

PMID- 12227711
TI  - Simultaneous catheter mapping of the pulmonary veins in focal atrial
      fibrillation: significance of rapid focal activation, effectiveness for catheter
      ablation.
AB  - Most focal atrial fibrillation (AF) is initiated by premature beats from the
      pulmonary veins (PV), and ablation of these foci can effectively cure AF. We
      investigated the efficacy of focal ablation and the role of rapid focal
      activation (RFA) in the maintenance of AF using simultaneous multisite catheter
      mapping in four PVs. Forty-two patients with frequent attacks of paroxysmal AF
      were included in the study population. Bipolar electrograms were simultaneously
      recorded from all four PVs. RFA was determined at AF onset, during sustained AF,
      or just before the spontaneous termination of AF. RFA was continuously observed
      not only at a triggered PV, but also at all sites including an opposite non
      triggered PV, coronary sinus and high right atrium in sustained AF (>10 minutes),
      whereas RFA was observed only in the triggered PV and not at the other sites in
      nonsustained AF. Once RFA ceased, AF terminated immediately. After a mean follow
      up of 21 months, focal ablation had eliminated AF without drugs in 24 patients
      (57%). The technique of simultaneous mapping of the PV using microcatheters is a
      feasible and effective method for mapping and ablation of focal AF originating
      from the PV. RFA arising from PVs is important not only as a trigger of onset,
      but also in the maintenance of AF.

PMID- 12227712
TI  - Role of signal-averaged electrocardiograms for predicting the inducibility of
      ventricular fibrillation in the syndrome consisting of right bundle branch block
      and ST segment elevation in leads V1-V3.
AB  - Right bundle branch block and ST segment elevation (RBBB-STE) in the right
      precordial leads have been reported as a distinct clinical and
      electrocardiographic syndrome in patients prone to ventricular fibrillation (VF)
      in the absence of structural heart disease (Brugada syndrome). The purpose of the
      study was to investigate the role of signal averaged electrocardiogram (SAECG) in
      identifying patients at high risk among asymptomatic RBBB-STE patients. Thirteen
      patients with the RBBB-STE ECG were identified. Symptoms were: syncope (n=3,
      cases 1, 3, and 11), atypical chest pain (n=3, cases 4, 10, and 12) and
      palpitations (n=2, cases 6, and 7). The other 5 patients were asymptomatic. SAECG
      and programmed electrical stimulation (PES) were conducted in all patients. Body
      surface late potentials (LPs) were present in 7 of 13 patients before PES. Vf was
      induced in 6 of 7 LP positive patients. Vf was induced in 3 of 6 LP negative
      patients, but LP became positive in 2 of 3 patients in whom Vf was induced. One
      patient with syncope due to VF (case 1), 1 patient without symptoms who died
      suddenly during follow up (case 2), and 1 asymptomatic patient (case 9) showed
      reproducibly positive LP. In a patient (case 9) with positive LP at baseline, LP
      transiently became negative during follow up. In RBBB-STE patients, reproducibly
      positive LP is at risk for malignant ventricular arrhythmias and sudden death.
      Repeated SAECG recording may be useful for screening high-risk patients who
      should receive electrophysiological study among asymptomatic RBBB-STE patients.

PMID- 12227713
TI  - Short and long term survival of surgical treatment of left ventricular aneurysms:
      ten years experience.
AB  - Although surgical treatment of left ventricular aneurysms has been performed for
      a long time, it is still a point of debate. In this study, we investigated 159
      patients who had undergone surgery for a left ventricular aneurysm in our clinic
      between 1985 and 1994. Perioperative mortality, long term survival rates, and
      parameters which probably affect these ratios were evaluated. All of the patients
      except one were followed by clinical records, mail or phone. Classic linear
      repair (111 cases), plication (46 cases), and Dor plasty (2 cases) were
      performed. Revascularisation procedure was also performed in 140 (88%) cases. The
      average number of distal anastomosis was 2.6. Twenty cases (12.6%) died in the
      perioperative period. The most important parameter which affected early mortality
      was the requirement for an intra-aortic balloon pump in the postoperative period.
      Mean follow-up duration was 47 +/- 35 months. Forty-two late deaths occurred in
      this period. The overall 5-year survival rate was 71%. Predictors for long term
      mortality were related to preoperative left ventricular function, presence of
      congestive heart failure, and poor functional capacity. The type of surgery did
      not affect short and long term survival. The functional capacity of the survivors
      was improved. In conclusion, surgical treatment of left ventricular aneurysms
      with classic linear repair and plication had acceptable short and long term
      survival rates and improved functional capacity. The most important predictor of
      survival in either the early or late postoperative period was preoperative left
      ventricular function.

PMID- 12227714
TI  - Cardiovascular involvement in Behcet's disease.
AB  - The incidence and nature of cardiac involvement in Behcet's disease are not yet
      clearly documented. We first used transesophageal echocardiography in combination
      with resting and signal averaged electrocardiography to define cardiac
      involvement in Behcet's patients. Transthoracic and multiplane transesophageal
      echocardiography, and resting and signal averaged electrocardiography were
      performed in 35 Behcet's disease patients (9 women and 26 men, mean age: 38 +/-
      12 years) and 30 normal subjects. Higher incidences of interatrial septum
      aneurysm (31% to 6%), mitral valve prolapse (25% to 3%), mitral regurgitation
      (40% to 6%) and aneurysmal dilatations of sinus valsalva and ascendan aorta were
      observed in the Behcet's disease patients than in the normal subjects. Mean QT
      dispersion and mean corrected QT dispersion values were significantly greater in
      the patients with Behcet's disease. Patients with interatrial septum aneurysm
      (and/or PFO), valvular dysfunction or proximal aorta dilatation had greater QT
      dispersion values than thase without these pathologies in the Behcet's group (63
      +/- 11 vs 44 +/- 19 ms, 58 +/- 23 vs 41 +/- 24 and 60 +/- 27 vs 42 +/- 23 ms
      respectively, P<0.05). Positive signal averaged electrocardiography parameters
      were detected in 18 (51%) Behcet's disease patients compared with one (3%) in
      controls (P<0.001). Dilatation of the proximal aorta, interatrial septal
      aneurysm, mitral valve prolapse, and mitral regurgitation are the common findings
      of cardiac involvement in Behcet's disease. Increased dispersion of ventricular
      repolarisation and positive late potentials are also detected. QT dispersion is
      significantly higher in patients with these cardiac abnormalities. These findings
      suggest that cardiac involvement in this disorder is a diffuse process which
      involves both cardiac structure and vascular elements.

PMID- 12227715
TI  - The Na+-Ca2+ exchanger contributes to beta-adrenoceptor mediated positive
      inotropy in mouse heart.
AB  - The L-type Ca2+ current (I(Ca,L)) plays an important role in the regulation of
      cardiac contractility. However, there is little data with regard to the
      significance of the I(Ca,L)-independent mechanism of beta-adrenoceptor mediated
      positive inotropy. The effects of isoproterenol (ISO) on I(Ca,L) and
      contractility in the presence of Ca2+ channel blockers (nifedipine, verapamil)
      were examined in adult mouse ventricular myocytes. ISO increased contractility
      over the level before the administration of Ca2+ channel blocker, although it had
      a very limited effect on I(Ca,L). The positive inotropy of ISO disappeared after
      administration of Ni2+, an inhibitor of the Na+-Ca2+ exchanger. The addition of
      ISO after nifedipine pretreatment also increased the [Ca2+]i transient over the
      control level and the application of Ni2+ or KB-R7943, a selective Na+-Ca2+
      exchange inhibitor (reverse mode), abolished the increase in [Ca2+]i transient.
      Therefore, an I(Ca,L)-independent mechanism plays a significant role in beta
      adrenoceptor mediated positive inotropy. The Na+-Ca2+ exchanger is necessary for
      the development of this action.

PMID- 12227717
TI  - Spinal epidural hematoma following tissue plasminogen activator and
      heparinization for acute myocardial infarction.
AB  - The case of a 43-year-old Taiwanese man who presented with spinal epidural
      hematoma following intravenous administration of recombinant tissue plasminogen
      activator (rTPA) and heparin therapy for acute myocardial infarction (AMI) is
      reported. Upper back pain and progressive neurological dysfunction ensued,
      secondary to spinal epidural hematoma with spinal cord compression. The patient
      did not recover neurologic function postsurgically, possibly because the
      operation was delayed. In conclusion, cardiologists should be alert to this rare,
      severe complication of rTPA and should perform early laminectomy (in < or = 36
      hours for those with complete deficit and in < or = 48 hours for those with
      incomplete deficit) if possible.

PMID- 12227716
TI  - Lysophosphatidylcholine potentiates the mitogenic effect of various vasoactive
      compounds on rabbit aortic smooth muscle cells.
AB  - We examined the mechanism of action of lysophosphatidylcholine (lyso-PC), which
      is suggested to be involved in the pathogenesis of atherosclerosis and
      inflamatory disorders, and its interaction with well-known vasoactive compounds
      such as hydrogen peroxide (H2O2), thromboxane A2 (TX-A2), serotonin (5-HT),
      angiotensin II (Ang-II), endothelin-1 (ET-1), or urotensin II (U-II) on VSMC
      proliferation. Growth-arrested rabbit VSMCs were incubated with given
      concentrations of lyso-PC with H202, TX-A2, 5-HT, Ang-II, ET-1, or U-II.
      [3H]Thymidine incorporation into DNA was measured as an index of VSMC
      proliferation. Lyso-PC induced a maximal effect on [3H]thymidine incorporation at
      a concentration of 15 microM (156%), and its effect was significantly inhibited
      by the phospholipase C inhibitor U73122 (10 microM), the intracellular
      antioxidant NAC (400 microM), and the NADPH oxidase inhibitor diphenylene
      iodonium (1 microM), but not by the MAPK kinase inhibitor (10 microM). H2O2, TX
      A2, 5-HT, Ang-II, ET-1, or U-II also stimulated [3H]thymidine incorporation in a
      dose-dependent manner. A non-mitogenic concentration of lyso-PC (5 microM)
      significantly potentiated the effect of low concentrations of H2O2 (0.1 microM,
      110 to 222%), TX-A2 (5 microM, 120 to 202%), 5-HT (5 microM, 182 to 259%), Ang-II
      (0.5 microM, 167 to 304%), ET-1 (0.01 microM, 139 to 297%), or U-II (0.025
      microM, 120 to 332%) on [3H]thymidine incorporation. The results suggest that
      lyso-PC acts synergistically with the vasoactive compounds H2O2, TX-A2, 5-HT, Ang
      II, ET-1, or U-II in inducing VSMC proliferation, which may play an important
      role in the progression of atherosclerosis.

PMID- 12227718
TI  - Left circumflex coronary artery bridging.
AB  - Myocardial bridging most frequently occurs on the left anterior descending
      coronary artery and may cause ischemia and related complications. Right coronary
      artery myocardial bridges (MB) are rare. We report a patient with an unusual
      coronary bridge, a left circumflex coronary artery bridge, who presented with
      exercise-induced angina pectoris that was relieved with medical therapy.

PMID- 12227719
TI  - Subclavian and pulmonary steal phenomenon in isolated left subclavian artery with
      left lung agenesis.
AB  - Isolated left subclavian artery has been documented to be associated with several
      congenital cardiac defects, including tetralogy of Fallot and transposition of
      the great arteries. In some cases subclavian or pulmonary artery steal phenomenon
      may occur when the isolated left subclavian artery connects to the main pulmonary
      artery via a ductus arteriosus. The isolated left subclavian artery may be part
      of the cardiac manifestations in multiple congenital anomalies, such as VACTERL
      association. We describe subclavian and pulmonary steal phenomenon in a neonate
      with complex congenital heart disease, including an isolated left subclavian
      artery, and left lung agenesis. An isolated left subclavian artery is rare and
      its association with agenesis of the left lung has not been reported previously.

PMID- 12227720
TI  - Oxidative stress in chronic renal failure as a cardiovascular risk factor.
AB  - Myocardial injury has been shown to be the most critical factor influencing
      quality of life and mortality in patients with chronic renal failure. Oxidative
      stress has been postulated to be an important risk factor for cardiovascular
      disorders. One reason for oxidative stress in patients with renal failure is the
      underlying disease itself. Renal toxicity, ischemia/reperfusion and immunological
      disorders of the kidney result in an elevated formation of reactive oxygen
      species active in the pathogenesis of kidney disease. However, treatment
      procedures were also shown to induce oxidative stress. Increased formation of
      free radicals leads to an accelerated lipid peroxidation (LPO). Furthermore,
      secondary aldehydic LPO products, e.g. malondialdehyde (MDA) and 4-hydroxynonenal
      (HNE), are formed which were shown to deplete antioxidants, inhibit protein
      syntheses, mitochondrial respiration, and enzyme functions. F2-isoprostanes, also
      metabolites of polyunsaturated fatty acids, represent an additional in vivo
      marker of oxidative stress. Both isoprostanes and aldehydic LPO products can be
      removed by hemodialysis, however, this suggests only in part their binding to
      other molecules which cause tissue damage. Protein carbonyls are end-products of
      such interventions. Oxysterols, another form of free-radical initiated oxidation
      products, were shown to initiate atherosclerosis and plaque formation increasing
      dramatically the risk of coronary heart disease. Today there is no doubt that the
      correction of the oxidant/antioxidant imbalance in patients with chronic renal
      failure is an important approach for the reduction of the risk of those patients
      to develop cardiovascular disorders. The complete correction of renal anemia
      represents an effective means of strengthening antioxidant capacity and,
      therefore, of reducting cardiovascular risk potential.

PMID- 12227721
TI  - Pharmacotherapeutic strategy in heart failure.
AB  - Chronic pharmacotherapy of congestive heart failure deals with its special
      pathophysiology and acts on different sites of the cardiorenal axis. The standard
      therapy consists of diuretics, ACE-inhibitors and beta-blockers and can be
      supplemented by cardiac glycosides, if heart failure worsens. Cardiac glycosides
      are also administered if tachycardic arrhythmias occur. Aldosterone-antagonists
      are combined with standard therapy in NYHA III - IV to counteract cardiac
      remodelling. AT1-antagonists are indicated when ACE-inhibitors are
      contraindicated or cannot be administered because of side-effects. Combination
      with ACE-inhibitors and AT1-antagonists may be of benefit for the patient since
      morbidity and hospitalization decrease.

PMID- 12227722
TI  - Elevated serum concentration of cardiotoxic lipid peroxidation products in
      chronic renal failure in relation to severity of renal anemia.
AB  - Patients with end-stage renal disease undergoing hemodialysis (HD) are exposed to
      oxidative stress. Increased levels of malondialdehyde (MDA) and 4-hydroxylnonenal
      (HNE) were found in plasma of uremic patients indicating accelerated lipid
      peroxidation (LPO) as a consequence of multiple pathogenetic factors. The
      catabolism and action of those products was already intensively studied. As
      highly reactive metabolites they are able to bind to proteins, nucleic acids, and
      other molecules. Doing so, they exert molecular signal effects in cells and are
      able to exacerbate tissue and organ damage, e.g. cardiotoxic effects. Since renal
      anemia was shown to promote oxidative stress as well, the aim of our
      investigation was to examine its role in HD patients. Therefore, two groups of HD
      patients were investigated (group I Hb < 10 g/dl, group II Hb > 10 g/dl) and
      serum concentrations of MDA, HNE, and of protein carbonyls, a marker for protein
      oxidation, were determined. All HD patients had significantly higher levels of
      the LPO products MDA and HNE compared with controls. However, group I patients
      showed higher MDA and HNE concentrations compared to group II patients. The same
      result could be seen for protein carbonyls. During HD concentration of both LPO
      products decreased. However, this was not the case for protein carbonyls. These
      results lead to the conclusion that optimized correction of the renal anemia may
      result in a significant reduction of oxidative stress and therefore in the
      reduction of organ tissue damage. In this way correction of renal anemia will
      reduce the cardiovascular risk and comorbidity of HD patients improving their
      prognosis.

PMID- 12227723
TI  - Homocysteine in chronic renal failure in relation to renal anemia and to
      oxidative stress parameters 4-hydroxynonenal and malondialdehyde.
AB  - Homocysteine serum levels were measured in patients with end-stage renal disease
      in relation to severity of renal anemia and oxidative stress parameters such as 4
      hydroxynonenal (HNE) and malondialdehyde (MDA). The predialytic homocysteine
      serum levels of the patients are five times as high as in healthy controls. It
      was found that homocysteine does not correlate to hemoglobin concentration and to
      oxidative stress, but rather to parameters of nutrition status such as albumine
      concentration and protein catabolic rate. The homocysteine accumulation
      represents a cardiovascular risk factor which is statistically independent of
      oxidative stress, but dependent on nutrition or energy status in patients with
      chronic renal failure.

PMID- 12227724
TI  - Adaptation of glutathion-peroxidase activity to oxidative stress occurs in
      children but not in adult patients with end-stage renal failure undergoing
      hemodialysis.
AB  - Lipid peroxidation (LPO) products formed after reaction of free radicals with
      membrane lipids are involved in the pathogenesis of cardiac diseases. Also in
      patients with end-stage renal disease (ESRD) LPO was shown to be accelerated and
      concentrations of non-enzymatic antioxidants were measured lower than in control
      subjects. However, up to now only limited knowledge about the role of antioxidant
      enzymes was available. Whether or not activity of those antioxidants might be
      induced due to oxidative stress in ESRD patients is not known. To answer the
      question the activity of 3 enzymatic antioxidants, superoxide dismutase (SOD),
      catalase (CAT), and glutathion peroxidase (GPx), was measured in red blood cells
      of the ESRD patients undergoing hemodialysis (2 groups: children and adults) and
      matching controls. LPO in these subjects was determined by measurement of the LPO
      product 4-hydroxynonenal (HNE) in blood plasma. Plasma HNE was significantly
      increased by factor 3 in both patient groups children and adults compared to the
      control groups. The activity of the enzymatic antioxidants was measured
      differently. While SOD was significantly lower in patients (children and adults)
      than in the matching controls this was not the case for catalase and GPx. While
      GPx activity in adult patients was comparable to that in the control groups
      (childrens and adults), the GPx in children with ESRD was almost twice as high
      than in the other groups. Since children were shown to have higher levels of
      glutathion, activated GPx might be a sign of adaptation of these children to the
      increased rate of oxidation.

PMID- 12227725
TI  - The correction of anemia in severe resistant heart failure with erythropoietin
      and intravenous iron prevents the progression of both the heart and the renal
      failure and markedly reduces hospitalization.
AB  - Both Congestive Heart Failure (CHF) and Chronic Renal Failure (CRF) are
      increasing steadily in the community. We propose that there is a vicious circle
      established whereby CHF and CRF both cause anemia and the anemia then worsens
      both the CHF and CRF causing more anemia and so on. We call this the Cardio Renal
      Anemia (CRA) syndrome. By the combination of active treatment of the CHF and
      control of the anemia with subcutaneous erythropoietin and intravenous iron, the
      progression of both the CHF and the CRF can be slowed or stopped in most cases,
      the quality of life improved and the need for recurrent hospitalization reduced.
      This will involve cooperation between internists, cardiologists, and
      nephrologists to allow early and maximal therapy of both the CHF and the anemia.

PMID- 12227726
TI  - Arterial hypertension and left ventricular hypertrophy in hemodialysis patients.
AB  - The high prevalence of left ventricular hypertrophy (LVH) among hemodialysis
      patients may be a consequence of inadequate diagnosis and treatment of arterial
      hypertension (AH). AH is not adaquately controlled in hemodialysis patients
      probably due to an underestimation of the effective BP load due to the
      unreliability of clinical BP readings in this population. Furthermore, BP
      reduction induced by dialysis ultrafiltration is not an acceptable criterion for
      discontinuing antihypertensive therapy, particularly when LVH coexists. Indeed,
      the few available interventional studies have demonstrated that strict BP
      control, together with anemia correction and dialysis adequacy improvement, can
      induce significant regression of the LVH of hemodialysis patients. Moreover, the
      decrease of SBP, particularly as a result of ACE-inhibitor therapy, is the most
      important predictor of LVH regression. Finally the use of ABPM and of
      echocardiography are recommended for correctly detecting an underlying AH and for
      tailoring and monitoring the effectiveness of antihypertensive therapy in
      dialysis patients with LVH.

PMID- 12227727
TI  - Renal anemia and its hemodynamic response--findings invasively determined over a
      period of 20 years.
AB  - Among the uremia-associated risk factor, which can be influenced today, anemia is
      considered most relevant because it induces functional and organic alterations of
      cardiac/circulatory function. Research concerning influence of the anemia on the
      pulmonary hemodynamic and cardiac output (CO) in pre-uremic patients are not
      available up to now. Cardiac and circulatory function of 52 patients were
      examined before initiation of dialysis therapy using a Swan-Ganz thermodilution
      catheter. After excluding patients with impaired cardiac pump function the
      results of 31 of the 52 patients could be analyzed. They were divided into two
      groups (Hb > resp. < 7.0 g/dl): in patients with severe anemia (Hb 5.7 +/- 0.6
      g/dl; n = 7) cardiac index was higher (4.8 +/- 0.4 1/min/m2 < 0.01) compared with
      the other group (Hb 9.8 +/- 1.7 g/dl; n = 24; CI 3.9 +/- 1.1 1min/m2). The
      increase of cardiac index caused by anemia correlated with increased stroke
      volume and heart rate and lowered pulmonary and peripheral resistance. Patients
      with severe anemia showed a tendency to an impaired cardiac index below Hb < 5-6
      g/dl. The hypercirculation did not cause an increase of the pulmonary arterial
      and pulmonary wedge pressure. Particularly in the case of already existing
      myocardial damage and coronary arteriosclerosis the presence of anemia and renal
      insufficiency leads to a highly increased morbidity and mortality. This "cardio
      renal anemia-syndrom" is responsible for frequent refractory heart failure.
      Disturbances of cardiac/circulatory function are observed in pre-uremic patients
      three times more frequently than in patients after myocardial infarction. Early
      correction of anemia seems to reduce the risk of fatal cardial complications and
      to improve the quality of life and the prognosis of pre-uremic patients.

PMID- 12227728
TI  - Should hemoglobin be normalized in uremic patients?
AB  - Cardiovascular disease is virtually a sine qua non of chronic kidney disease, as
      is poor quality of life. Dialysis patient for example, have cardiovascular death
      rates 10 - 20 times those of the general population. Recent estimates indicate
      that at least half of all patients starting dialysis therapy will have an
      admission for a major cardiovascular event within 5 years, of which cardiac
      failure is the most common. Both experimental and clinical studies suggest that
      the cardiovascular system in uremia is in a state of premature senescence, one
      which is poorly suited to the supraphysiological hemodynamic demands to which it
      is subjected. Most patients develop cardiomyopathy, which clearly predisposes to
      cardiac decompensation. Anemia and hypertension are the most obvious modifiable
      overload parameters in uremic patients. Several prospective observational studies
      have demonstrated anemia to be an independent risk factor for each step in the
      process leading from hemodynamic overload, through maladpative left ventricular
      enlargement to left ventricular failure and death. This process starts with
      declining renal function, long before end-stage renal disease, the traditional
      time at which intervention has started to be seriously considered. The case for
      normal hemoglobin in patients with chronic kidney disease is still greatly
      disputed. Observational studies, which examine left ventricular size, quality of
      life, functional status, hospitalization and survival, are overwhelmingly
      supportive. Intervention trials, to date, suggest clear benefits of a
      physiological approach to anemia management in terms of quality of life, and
      likely benefits in terms of left ventricular stress minimisation and associated
      remodelling. Whether these translate into a reduction in outcomes like cardiac
      failure or death remains an unanswered question.

PMID- 12227729
TI  - Cardiovascular changes in chronic renal failure--pathogenesis and therapy.
AB  - Cardial death caused by ischemia, which is not necessarily connected with
      coronary arterial changes, represents the main death cause in chronic renal
      failure patients. The present overview article compiles the latest findings on
      structural and functional changes of the heart and vessels in uremia, which have
      a potential effect on the ischemia tolerance of the myocardium and thus help to
      explain the high cardiovascular mortality in chronic renal failure. The
      cardiovascular structural changes comprise: 1. A left ventricular myocardium
      hypertrophy, 2. an interstitial myocardium fibrosis and 3. changes in the
      myocardial microcirculation like, above all, a rarefaction of the intramyocardial
      capillaries with increase in the intercapillary oxygen diffusion passage and a
      vascular wall thickening of intramyocardial arteries. In addition, characteristic
      metabolic changes, like for instance a decrease of phosphates rich in energy,
      which contribute likewise to a heightened ischemia sensitivity of the myocardium.
      At the same time an involvement of extra-myocardial vascular changes is also
      probable in the development of the prognostically unfavorable myocardium
      hypertrophy in chronic renal failure. These extracardial vascular changes
      consist, above all, of a wall thickening of the aorta, of the peripheral arteries
      and veins with reduction of the share of elastic fiber, of an increase in the
      extracellular matrix and of a diffuse media calcification and lead to an increase
      in vascular stiffness and to reduction of aortal compliance.

PMID- 12227730
TI  - Clinical studies on the therapy of heart failure using ACE-inhibitors and AT1
      receptor blockers--does combination treatment make sense?
AB  - In all industrial nations the number of patients with heart hailure is
      increasing. Pharmacological treatment with Angiotensin-converting enzyme (ACE)
      inhibitors and beta blockers improve survival and reduce hospitalization in these
      patients. Inspite of these therapies, morbidity and mortality remains
      problematic. Possibly phenomena like the genetic induced Angiotensin-II-escape
      are responsible for the individual response in patients. Regarding their
      different pharmacological effects the new group of Angiotensin-II type 1 receptor
      (AT1) blockers seem to be promising for the treatment of heart failure. In trials
      like ELITE 1, ELITE 2 and Val-HeFT it could be demonstrated that AT1-blockers and
      ACE-inhibitors have a comparable effect in improving survival of heart failure
      patients. In the Val-HeFT study the combination of an ACE-inhibitor and an AT1
      blocker reduce hospitalization and improve quality of life of heart failure
      patients compared with single treatment using an ACE-inhibitor or AT1-blocker.
      Mortality showed no significant difference. Before a final assessment of the
      combination treatment with ACE-inhibitors and AT1- blockers in heart failure
      patients we need more studies like the present CHARM-study.

PMID- 12227731
TI  - Regression of left ventricular hypertrophy in hemodialysis patients is possible.
AB  - Regression of left ventricular hypertrophy in hemodialysis patients is possible.
      Left ventricular hypertrophy represents the major risk factor for cardiac
      morbidity and mortality. Therefore, their regression is mandatory. Since the
      causes of uremia-associated left ventricular hypertrophy are multifactorial,
      various therapeutic options can be considered: optimal control of arterial
      hypertension and volume status, optimal correction of metabolic acidosis, best
      possible correction of hypoalbuminemia and severe secondary hyperparathyroidism,
      modern pharmacotherapeutic strategy for the treatment of heart failure (use of
      angiotensin-converting enzyme inhibitors in combination with angiotensin II
      receptor blockers and beta-blockers) and total correction of renal anemia.
      Following the proposed therapeutic strategies we could, by using
      echocardiography, distinguish in 100 hemodialysis patients the following 3 groups
      (on the average after 1.5 years): 36 patients with initially normal left
      ventricular mass index (LVMI (g/m2), F < 110; M < 130) maintained normal (group
      1); in 31 patients with moderately increased LVMI full regression resulted (group
      2); 33 patients with severely increased LVMI (group 3) had to be further divided
      into 2 sub-groups: 22 patients with significant improvement of LVMI, 11 patients
      with no, regression. For the first time we were able to show that it is possible
      to maintain initially normal LVMI during long-term treatment and to achieve
      complete regression and significant improvement of LVMI in our patients. However,
      since LVMI requires a long time to develop, a similarly long time must be
      estimated for its regression. However, 11 patients remained therapeutically
      resistant. In this group, severe heart diseases were often combined and highly
      prevalent, including ischemic heart and valve diseases and end-stage dilatative
      cardiomyopathy. These patients had to be transferred to cardiac surgery. Anemia
      is considered to be one of the most important factors for the development of left
      ventricular hypertrophy. Therefore, total correction of renal anemia has to be
      strongly recommended in addition to other measures of our therapeutic strategy to
      maintain full or significant regression of left ventricular hypertrophy.

PMID- 12227732
TI  - Combinatorial algorithms for design of DNA arrays.
AB  - Optimal design of DNA arrays requires the development of algorithms with two-fold
      goals: reducing the effects caused by unintended illumination (border length
      minimization problem) and reducing the complexity of masks (mask decomposition
      problem). We describe algorithms that reduce the number of rectangles in mask
      decomposition by 20-30% as compared to a standard array design under the
      assumption that the arrangement of oligonucleotides on the array is fixed. This
      algorithm produces provably optimal solution for all studied real instances of
      array design. We also address the difficult problem of finding an arrangement
      which minimizes the border length and come up with a new idea of threading that
      significantly reduces the border length as compared to standard designs.

PMID- 12227733
TI  - Protein array technology: the tool to bridge genomics and proteomics.
AB  - The generation of protein chips requires much more efforts than DNA microchips.
      While DNA is DNA and a variety of different DNA molecules behave stable in a
      hybridisation experiment, proteins are much more difficult to produce and to
      handle. Outside of a narrow range of environmental conditions, proteins will
      denature, lose their three-dimensional structure and a lot of their specificity
      and activity. The chapter describes the pitfalls and challenges in Protein
      Microarray technology to produce native and functional proteins and store them in
      a native and special environment for every single spot on an array, making
      applications like antibody profiling and serum screening possible not only on
      denatured arrays but also on native protein arrays.

PMID- 12227734
TI  - Microarray data representation, annotation and storage.
AB  - Management and analysis of the huge amounts of data produced by microarray
      experiments is becoming one of the major bottlenecks in the utilization of this
      high-throughput technology. We describe the basic design of a microarray gene
      expression database to help microarray users and their informatics teams to set
      up their information services. We describe two data models--a simpler one called
      ArrayExpressB and the complete model ArrayExpressC, and discuss some
      implementation issues. For latest developments see http:
      wwwebi.ac.uk/arrayexpress

PMID- 12227735
TI  - High-density genechip oligonucleotide probe arrays.
AB  - High-density DNA probe arrays provide a highly parallel approach to nucleic acid
      sequence analysis that is transforming gene-based biomedical research.
      Photolithographic DNA synthesis has enabled the large-scale production of
      GeneChip probe arrays containing hundreds of thousands of oligonucleotide
      sequences on a glass "chip" about 1.5 cm2 in size. The manufacturing process
      integrates solid-phase photochemical oligonucleotide synthesis with lithographic
      techniques similar to those used in the microelectronics industry. Due to their
      very high information content, GeneChip probe arrays are finding widespread use
      in the hybridization-based detection and analysis of mutations and polymorphisms
      ("genotyping"), and in a wide range of gene expression studies.

PMID- 12227737
TI  - The use of MassARRAY technology for high throughput genotyping.
AB  - This chapter will explore the role of mass spectrometry (MS) as a detection
      method for genotyping applications and will illustrate how MS evolved from an
      expert-user-technology to a routine laboratory method in biological sciences. The
      main focus will be time-of-flight (TOF) based devices and their use for analyzing
      single-nucleotide-polymorphisms (SNPs, pronounced snips). The first section will
      describe the evolution of the use of MS in the field of bioanalytical sciences
      and the protocols used during the early days of bioanalytical MALDI TOF mass
      spectrometry. The second section will provide an overview on intraspecies
      sequence diversity and the nature and importance of SNPs for the genomic
      sciences. This is followed by an exploration of the special and advantageous
      features of mass spectrometry as the key technology in modern bioanalytical
      sciences in the third chapter. Finally, the fourth section will describe the
      MassARRAY technology as an advanced system for automated high-throughput analysis
      of SNPs.

PMID- 12227736
TI  - Oligonucleotide scanning arrays: application to high-throughput screening for
      effective antisense reagents and the study of nucleic acid interactions.
AB  - Oligonudeotide scanning arrays are useful tools in the study of nucleic acid
      interaction. Such arrays of oligonucleotides, corresponding to a full set of
      complements of a known sequence, can be readily made in a single series of
      coupling reactions, adding each nudeotide in the complement of the target
      sequence in turn. The synthesis is carried out on the surface of a solid
      substrate such as glass or polypropylene that has been modified to allow
      nucleotide coupling. A mask is used to apply the DNA synthesis reagents in a
      defined area and is moved by a fixed step size after each coupling reaction so
      that consecutive couplings overlap a portion of the previous one. The size of the
      mask and the displacement at each coupling determine the length of the
      oligonucleotides. A radiolabeled or fluorescently tagged target sequence is
      hybridised to a scanning array and its interaction with the complementary
      oligonudeotides is displayed as a hybridisation signal. It is thus possible to
      determine the exact sequence and lengths of large numbers of interacting
      sequences in a single hybridisation experiment. The array image is analysed using
      a computer program (xvseq) that calculates quantitative measurements of the
      binding strengths. We have found scanning arrays a useful tool not only to find
      effective antisense reagents, but also to study RNA folding and the mechanisms of
      heteroduplex formation. In this article, we discuss the format of these arrays,
      the technology used to fabricate and to read them, and their applications.

PMID- 12227738
TI  - Sequencing by hybridization (SBH): advantages, achievements, and opportunities.
AB  - Efficient DNA sequencing of the genomes of individual species and organisms is a
      critical task for the advancement of biological sciences, medicine and
      agriculture. Advances in modern sequencing methods are needed to meet the
      challenge of sequencing such megabase to gigabase quantities of DNA. Two possible
      strategies for DNA sequencing exist: direct methods, in which each base position
      in the DNA chain is determined individually (e.g., gel sequencing or
      pyrosequencing), and indirect methods, in which the DNA sequence is assembled
      based on experimental determination of oligonucleotide content of the DNA chain.
      One promising indirect method is sequencing by hybridization (SBH), in which sets
      of oligonucleotides are hybridized under conditions that allow detection of
      complementary sequences in the target nucleic acid. The unprecedented sequence
      search parallelism of the SBH method has allowed development of high-throughput,
      low-cost, miniaturized sequencing processes on arrays of DNA samples or probes.
      Newly developed SBH methods use DNA ligation to combine relatively small sets of
      short probes to score potentially tens of millions of longer oligonucleotide
      sequences in a target DNA. Such combinatorial approaches allow analysis of DNA
      samples of up to several kilobases (several times longer than allowed by current
      direct methods) for a variety of DNA sequence analysis applications, including de
      novo sequencing, resequencing, mutation/SNP discovery and genotyping, and
      expression monitoring. Future advances in biochemistry and implementation of
      detection methods that allow single-molecule sensitivity may provide the
      necessary miniaturization, specificity, and multiplexing efficiency to allow
      routine whole genome analysis in a single solution-based hybridization
      experiment.

PMID- 12227741
TI  - A new approach to heterofunctionalized dendrimers: a versatile triallyl chloride
      core.
AB  - A reactive triallyl chloride moiety was prepared as a suitable core for aliphatic
      polyether dendrons. In addition to allowing access to fourth generation
      dendrimers, this core contains three alkene functionalities that can be modified
      after dendrimer formation and used for further dendritic growth.

PMID- 12227742
TI  - Synthesis of bicyclic gamma-ylidenetetronates.
AB  - The bicyclic gamma-ylidenetetronate motif found in several Stemona alkaloids was
      prepared in a stereoselective manner by addition of lithium methyl tetronate to
      an alkoxy oxonium ion formed from a lactone. The corresponding mixed alkyl ketal
      obtained was subjected to a Lewis acid-base-promoted dealkoxylation reaction to
      deliver the desired products.

PMID- 12227743
TI  - S(N)1-like reactions of bicyclic alpha-amino ethers with sulfur, nitrogen, and
      carbon nucleophiles. Synthesis of 1-azabicyclo[3.2.2]nonanes functionalized at
      carbon C2 and C6 with complete stereocontrol.
AB  - [reaction: see text] In the presence of nucleophiles, Lewis acid mediated
      cleavage of alpha-amino ethers derived from quincorine and quincoridine affords a
      variety of C2-substituted and C6-vinylated 1-azabicyclo[3.2.2]nonanes. These are
      enantiopure and are formed in S(N)1-like reactions with complete stereocontrol.
      There is no leakage into 2-Nu en route to product 1-Nu or vice versa. Me(3)SiCN
      provides new Strecker-type alpha-amino nitriles. In the presence of TTMPP
      BF(3).OEt(2), the ketene acetal Me(2)C=C(OMe)OSiMe(3) delivers enantiopure
      bicyclic beta-amino acid esters.

PMID- 12227744
TI  - Supramolecular association of dopamine with immobilized fluorescent probes.
AB  - We have designed a two-step procedure to coat silica particles with fluorescent
      2,7-diazapyrenium dications. The electron-deficient character of the dications
      encourages the association of dopamine at the particle/water interface. The
      supramolecular event produces a significant decrease in the fluorescence
      intensity. Model binding studies with catechol and propylamine revealed that the
      interfacial complexation of dopamine is dominated by the interaction of its
      electron-rich dioxyarene fragment with the electron-deficient fluorophore in
      neutral aqueous environments.

PMID- 12227745
TI  - A multicomponent reaction for the one-pot synthesis of 4-aza-2,3
      didehydropodophyllotoxin and derivatives.
AB  - [reaction: see text] A convergent method has been found to prepare 4-aza-2,3
      didehydropodophyllotoxin and derivatives in a one-pot procedure. The mechanism of
      the reaction between tetronic acid, anilines, and benzaldehydes is discussed.

PMID- 12227746
TI  - A method for bioconjugation of carbohydrates using Diels-Alder cycloaddition.
AB  - Diels-Alder-type cycloaddition of an electronically matched pair of saccharide
      linked conjugated dienes and a dienophile-equipped protein gives neoglycoproteins
      at ambient temperature in pure water with a reaction half-life of approximately 2
      h. Uncoupled saccharides can be recovered by diafiltration with complete
      conservation of the diene moiety, thus allowing their repeated use. The procedure
      described is the first for creating a carbon-carbon covalent bond in the
      bioconjugation step between a saccharide and a protein.

PMID- 12227747
TI  - Influence of pi-stacking on the redox properties of oligothiophenes: (alpha
      alkyloligo-thienyl)para[2.2]cyclophanes.
AB  - [structure: see text] Oligothienyl-substituted paracyclophanes bearing alpha
      thienyl substituents, which block polymerization at these sites, undergo
      oxidation to form stable radical cations and dications. Splitting of the first
      voltammetric oxidation wave of stacked dimers into two single-electron processes
      corresponding to formation of the stacked mono(radical cation) and the stacked
      bis(radical cation) illustrates the influence of pi-stacking on the behavior of
      conjugated chains, which serve as models for stacked polarons in conjugated
      polymers.

PMID- 12227748
TI  - One-pot synthesis of symmetrical and unsymmetrical bisarylethynes by a
      modification of the sonogashira coupling reaction.
AB  - A modification of the Sonogoshira coupling reaction employing an amidine base and
      a substoichiometric amount of water generates symmetrical and unsymmetrical
      bisarylethynylenes in one pot through in situ deprotection of
      trimethylsilylethynylene-added intermediates.

PMID- 12227749
TI  - A novel thiourea-based dual fluorescent anion receptor with a rigid hydrazine
      spacer.
AB  - [structure: see text] A neutral receptor with a rigid hydrazine spacer, N-p
      (dimethylamino)benzamido-N'-phenylthiourea, was prepared, and its dual
      fluorescence in acetonitrile was found to show response toward the presence of
      anions such as AcO(-), H(2)PO(4)(-), HSO(4)(-), Br(-), Cl(-), F(-), and ClO(4)(-)
      with high sensitivity and selectivity toward AcO(-).

PMID- 12227750
TI  - Modulation of metal recognition by a novel calix[4]arene bearing two bipyridine
      units as a molecular gate.
AB  - [reaction: see text] A novel multiregulation system of ion recognition was
      constructed by utilizing a molecular gate. Interaction between the host and an
      Ag(+) is controlled with an Na(+) ion.

PMID- 12227751
TI  - Synthesis, complexation, and supramolecular assembly of 21,30-dithia-17,25
      dimethyl-1,4,7,10,13- pentaoxa[13.3.3](1,2,6)cyclophane.
AB  - [structure: see text] A crownophane consisting of a dithia[3.3]metacyclophane
      moiety was synthesized by employing a high dilution method. The crystal structure
      and complexation behavior of this crownophane was studied. A hydrogen-bonded
      linear supramolecular assembly using anion-Na(+)-crownophane-solvent as a synthon
      was observed in the solid state. This supramolecular assembly was also stabilized
      via an intermolecular S.H-C interaction.

PMID- 12227753
TI  - A new tri-orthogonal strategy for peptide cyclization.
AB  - A solid phase tri-orthogonal protection/cleavage strategy that uses acidic,
      basic, and neutral conditions is described. Strategically protected alpha-azido
      gamma-9-fluorenylmethyl-L-glutamate (1) and alpha-azido-epsilon-N-Fmoc-L-lysine
      (2) were incorporated into growing peptides on Wang resin using a novel azide
      protection strategy. These residues, separated by 1-3 monomers, were deprotected
      at the side chains and cyclized via lactam formation. The N-terminus was further
      functionalized to extend the chain. This method represents a straightforward
      protocol for peptide cyclization on solid support.

PMID- 12227752
TI  - Palladium-promoted cascade reactions of isonitriles and 6-iodo-N
      propargylpyridones: synthesis of mappicines, camptothecins, and
      homocamptothecins.
AB  - Ambient-temperature reactions of electron-rich aryl isonitriles with substituted
      6-iodo-N-propargylpyridones in the presence of silver carbonate and palladium
      acetate produce 11H-indolizino[1,2-b]quinolin-9-ones in good to excellent yield.
      Experimental evidence suggests that the process occurs though organopalladium
      rather than radical intermediates. It is applied to synthesis analogues of
      mappicine and camptothecin, including the silatecans DB-67 and DB-91 (homo-DB
      67).

PMID- 12227754
TI  - Synthesis, structure revision, and absolute configuration of (+)
      didemniserinolipid B, a serinol marine natural product from a tunicate Didemnum
      sp.
AB  - [structure: see text] En route to proving the absolute and relative
      stereochemistry, through synthesis, of (+)-didemniserinolipid B (1), the first
      natural serinolipid isolated from a tunicate Didemnum sp., it was discovered that
      the isolated natural product was in fact the 31-sulfate configured
      8R,9R,10R,13S,30S. This structural reassignment was only possible after the
      development of a microwave-assisted method for the sulfation of unreactive
      hydroxyl groups.

PMID- 12227755
TI  - Release of nitrosating species in the course of reduction of benzo-1,2,3,4
      tetrazine 1,3-dioxides.
AB  - [reaction: see text] The reduction of benzo-1,2,3,4-tetrazine 1,3-dioxides
      (BTDOs) 1 with Na(2)S(2)O(4) or SnCl(2) is suggested to proceed via intermediate
      N-nitrosobenzotriazoles 3 to afford benzotriazoles 2. The (15)N-labeling
      experiments exhibit that the N-3 atom of the tetrazine ring is incorporated into
      the nitroso group of 3 that is ultimately released into solution. It is possible
      that the biological activity of BTDOs is due to their ability to release
      nitrosating species, i.e., N-nitrosotriazol 3 or HNO(2), in the course of
      reduction.

PMID- 12227756
TI  - Concise total synthesis of (+)-brefeldin A: a combined beta-lactone/cross
      metathesis-based strategy.
AB  - [reaction: see text] A highly convergent total synthesis of (+)-brefeldin A that
      relies on a diastereoselective, beta-lactone-based cyclopentane synthesis
      combined with complex cross-metathesis reactions is described. The utility of
      beta-lactones for natural product synthesis and the versatility of cross
      metathesis in this context were demonstrated, including the tolerance of an
      epimerizable aldehyde and a beta-lactone.

PMID- 12227757
TI  - Ruthenium(II) porphyrin catalyzed tandem carbonyl ylide formation and 1,3-dipolar
      cycloaddition reactions of alpha-diazo ketones.
AB  - [reaction: see text] The ruthenium porphyrin-catalyzed reactions of diazo ketones
      with pi-unsaturated compounds via carbonyl ylide formation/cycloaddition cascade
      exhibit product yields and selectivities comparable to the analogous reactions
      with dirhodium carboxylates as catalysts. By grafting a ruthenium porphyrin on
      poly(ethylene glycol) (Zhang, J.-L.; Che, C.-M. Org. Lett. 2002, 4, 1911), a
      recyclable catalytic system is developed with over 5700 product turnovers
      attained for the reaction of 1-diazo-2,5-hexanedione with dimethyl
      acetylenedicarboxylate.

PMID- 12227759
TI  - Stereoselective total synthesis of dihydrocorynantheol.
AB  - [reaction: see text] A stereoselective synthesis of the indole alkaloid
      dihydrocorynantheol (1) from indole-3-acetic acid has been achieved by a sequence
      involving 9 as a key intermediate. The synthesis of the unsaturated lactam ring
      in 9 highlights a series of catalytic organometallic reactions featuring two ring
      closing metatheses and a zirconocene-catalyzed carbomagnesation. Since no
      protecting groups were used, the present synthesis of 1 is exceedingly concise,
      consisting of only eight distinct operations.

PMID- 12227758
TI  - Toward the total synthesis of disorazole A(1) and C(1): asymmetric synthesis of a
      masked southern segment.
AB  - [reaction: see text] A highly convergent asymmetric synthesis of the masked
      southern segment of the antimitotic agent disorazole A(1) involves a Sonogashira
      coupling between a C1'-C10' enyne and a suitably protected C11'-C19' vinyl
      iodide. The central E,Z,Z-triene moiety is masked as a more stable ynediene.

PMID- 12227760
TI  - Medium-dependent type selectivity in photoreactions of a crown ether-annelated
      dibenzobarrelene derivative.
AB  - [reaction: see text] A concept for modifying the photochemical properties of a
      dibenzobarrelene derivative by the combination of supramolecular assembly and
      solid-state photochemistry is presented. The irradiation of dibenzobarrelene 1b
      and alkali metal complexes thereof (1:1) in acetonitrile or benzene solution
      leads preferentially to the dibenzocyclooctatetraene 4b as the photoproduct. In
      contrast, the dibenzosemibullvalene 5b is formed as the main photoproduct in the
      solid state because of a strong cation effect.

PMID- 12227761
TI  - A new concept for the preparation of beta-L- and beta-D-2',3'-dideoxynucleoside
      analogues.
AB  - [reaction: see text] A new method for the synthesis of 2',3'-dideoxynucleoside
      analogues has been developed. An electrochemical activation of 2-substituted
      furans is followed by the coupling with a pyrimidine or purine base. This gives
      planar furyl nucleosides as key intermediates, which are hydrogenated cis
      selectively to give the corresponding beta-2',3'-dideoxynucleosides as racemic
      mixtures. An enzymatic kinetic resolution gives rise to beta-D- and beta-L
      configured derivatives in high optical purity. This is exemplified by the
      synthesis of beta-D- and beta-L-3'-deoxythymidine.

PMID- 12227762
TI  - Highly enantioselective photocyclization of 1-alkyl-2-pyridones to beta-lactams
      in inclusion crystals with optically active host compounds.
AB  - [reaction: see text] Upon photoirradiation of a 1:1 inclusion complex of (-)-3
      and 2-alkyl-1-pyridone (1) (R = Et, n-Pr, i-Pr, n-Bu, i-Bu) in the solid state,
      optically active beta-lactams (2) of 91-99.5% ee were obtained in good yield.

PMID- 12227763
TI  - Total stepwise solid-phase synthesis of oligonucleotide-(3'-->N)-peptide
      conjugates.
AB  - [structure: see text] An efficient total stepwise solid-phase synthesis of
      oligonucleotide-(3'-->N)-peptide conjugates is described that makes use of either
      a controlled pore glass support or macroporous polystyrene beads. Extending our
      previous homoserine linker approach, we prepared a range of conjugates containing
      one of four different cell or nuclear penetration peptides together with
      oligonucleotides containing 2'-deoxynucleoside or 2'-O-methylribonucleoside
      phosphodiesters, or gapmers containing 2'-deoxyphosphorothioates. The route also
      allows incorporation of a fluorescent label within the conjugate for cell uptake
      studies.

PMID- 12227764
TI  - Brasilane-type sesquiterpenoids from Laurencia obtusa.
AB  - [structure: see text] Three novel halogenated rearranged sesquiterpenes (1-3)
      have been isolated along with brasilenol (4) and epibrasilenol (5) from the
      organic extract of the red alga Laurencia obtusa, collected at Symi island in the
      Aegean Sea, Greece. The new metabolites possess the unusual skeleton of brasilane
      and contain the unprecedented 1,6-epoxy moiety. The structures of the new natural
      products, as well as their relative stereochemistry, were established by means of
      spectral data analyses, including two-dimensional NMR experiments along with
      molecular calculations.

PMID- 12227766
TI  - Novel intramolecular cyclopropanation reaction of unsaturated beta-keto esters.
AB  - [reaction: see text] Fused cyclopropane beta-keto esters are versatile
      intermediates for the synthesis of many biologically active natural products.
      Here we report a new intramolecular cyclopropanation reaction of unsaturated beta
      keto esters. In the presence of I(2), Et(3)N, and Lewis acids such as
      Mg(ClO(4))(2) and Yb(OTf)(3), beta-keto esters 1 bearing various olefin
      substituents were transformed to fused cyclopropanes 2 in a highly stereospecific
      manner with moderate to good yields. The mechanism of the reaction was also
      investigated.

PMID- 12227765
TI  - Angiogenesis inhibitor epoxyquinol a: total synthesis and inhibition of
      transcription factor NF-kappaB.
AB  - [reaction: see text] The asymmetric synthesis of the natural product (+)
      epoxyquinol A (1) and related epoxyquinoid dimers, employing a cascade
      oxidation/electrocyclization/Diels-Alder dimerization sequence, is reported. In
      addition, we show that 1 and related molecules inhibit activation of the
      transcription factor NF-kappaB.

PMID- 12227768
TI  - Sequential transition States and the valley-ridge inflection point in the
      formation of a semibullvalene.
AB  - [structure: see text] Two sequential transition states are calculated at the
      B3LYP/6-31G(d,p) level for the deazetization of 3b. The intrinsic reaction
      coordinate for loss of nitrogen passes through a transition state and then a
      valley-ridge inflection point and ultimately leads to the transition state for
      the Cope rearrangement of semibullvalene 4b. The energetic and geometrical
      consequences are discussed.

PMID- 12227767
TI  - DNA binding properties of oligodeoxynucleotides containing pyrrolidino C
      nucleosides.
AB  - We have incorporated pyrrolidino-C-nucleosides (pyrrolidino-pseudonucleosides)
      containing the base uracil and N-1-methyl uracil into oligodeoxynucleotides and
      compared their thermal duplex and triplex stabilities with unmodified or
      pseudouridine-containing oligodeoxynucleotides. We find relative destabilizations
      of triplex formation by ca. -13 to -1 degrees C per modification (relative to
      thymidine) in a strongly sequence dependent mode. Duplex formation is less
      destabilizing and more homogeneous with -4 to -2 degrees C per modification.

PMID- 12227769
TI  - Enantioselective hydrolysis of N-acylated alpha-amino esters at a biphasic
      interface: tandem reaction kinetic resolution using a chiral complexing agent.
AB  - [reaction: see text] Highly enantioselective hydrolytic kinetic resolutions of
      esters derived from N-acylated alpha-amino acids proceed rapidly at
      hydrocarbon/water interfaces in the presence of a proline-derived chiral
      selector. When performed in tandem with an enantioselective biphasic
      esterification reaction, esters of 100% enantiomeric excess are obtained

PMID- 12227770
TI  - Total syntheses of the marine pyrrole alkaloids polycitone A and B.
AB  - Polycitone B (2) was obtained in four steps from pyrrole dicarboxylic acid 3,
      including Friedel-Crafts reaction of the corresponding acid chloride with
      anisole. The conversion of 2 into polycitone A (1) was achieved in two steps via
      Mitsunobu alkylation of the pyrrolic NH group. The synthesis of polycitone A
      proceeds in 18% overall yield and offers the possibility of varying the
      substituents on the pyrrole ring.

PMID- 12227771
TI  - Conjugate addition of mixed diorganozinc compounds and functionalized organozinc
      cuprates to nitroolefins.
AB  - [reaction: see text] The copper-catalyzed conjugate addition of symmetrical and
      mixed diorganozinc compounds as well as functionalized diorganozinc cuprates to
      nitroolefins leads to synthetically versatile nitro compounds in moderate to good
      yields. Mixed TMSM-organozinc compounds are suitable reagents for conjugate
      addition, since the TMSM group is not being transferred. Ipso substitution is
      observed in the absence of a catalytic amount of copper(I) salt. The nitroalkene
      moiety in 3-nitroacrylates proved to be the predominant Michael acceptor.

PMID- 12227772
TI  - Application of high-field NMR and cryogenic probe technologies in the structural
      elucidation of poecillastrin a, a new antitumor macrolide lactam from the sponge
      poecillastra species.
AB  - Poecillastrin A (1), a new polyketide-derived macrolide lactam, was isolated from
      a deep-water collection of the marine sponge Poecillastra species. The structure
      of poecillastrin A (1) was assigned using NMR data acquired at 500 MHz with an
      inverse-detection cryogenic probe and at 800 MHz with a room-temperature probe.

PMID- 12227773
TI  - Bisbinaphthyl macrocycle-based highly enantioselective fluorescent sensors for
      alpha-hydroxycarboxylic acids.
AB  - [structure: see text] Bisbinaphthyl-based macrocycles are found to carry out
      highly enantioselective fluorescent recognition of alpha-hydroxycarboxylic acids.
      It is observed that within a certain concentration range, one enantiomer of the
      chiral acids can increase the fluorescence intensity of the macrocycles by 2-3
      fold, while the other enantiomer scarcely enhances the fluorescence. Such
      unusually high enantioselective responses make these macrocycles very attractive
      as fluorescent sensors in determining the enantiomeric composition of alpha
      hydroxycarboxylic acids.

PMID- 12227774
TI  - Regiochemistry of S-alkyl-substituted alkynes in Pauson-Khand reactions. Is a
      correlation with X-ray data and charge distribution calculations of the
      Co(2)(CO)(6)-alkyne complexes possible?
AB  - [reaction: see text] Pauson-Khand reactions (PKR) of RSCtbd1;CR' (6-10) yielded
      in all cases as the main product the regioisomer with the alkyl-S group disposed
      alpha to the CO group (16a-22a). Correlation of these results with X-ray data and
      charge distribution calculations of the corresponding dicobalthexacarbonyl
      complexes proves that a recently postulated "trans effect" in these complexes is
      not suitable for predicting the regiochemical outcome of the PKR unambiguously.

PMID- 12227775
TI  - Thermal isomerization of (3-butenyl)cyclopropane to norbornane.
AB  - [reaction: see text] (3-Butenyl)cyclopropane isomerizes thermally to norbornane
      and gives rise to many other products. Deuterium and carbon-13-labeled versions
      of (3-butenyl)cyclopropane have been prepared and isomerized, establishing that
      the formation of norbornane involves cleavage of the cyclopropyl C2-C3 bond.

PMID- 12227776
TI  - Acid-free aza Diels-Alder reaction of Danishefsky's diene with imines.
AB  - [reaction: see text] A highly efficient aza Diels-Alder reaction of Danishefsky's
      diene with imines was found to occur in methanol in the absence of any acids at
      room temperature to give corresponding 2-substituted dihydro-4-pyridone
      derivatives in high yields. This reaction can be also carried out in a three
      component one-pot reaction manner. The reaction was found to proceed through a
      Mannich-type condensation mechanism.

PMID- 12227777
TI  - Efficient preparation of c(2)-symmetrical chiral ferrocenyl diols by catalytic
      enantioselective reduction of diacylferrocenes.
AB  - [reaction: see text] Enantioselective borohydride reduction, catalyzed by the
      optically active beta-ketoiminato cobalt(II) complex, was successfully applied to
      the 1,1'-dialkanoyl- and 1,1'-dibenzoylferrocenes to afford the corresponding
      C(2)-symmetrical chiral ferrocenyl diols with high diastereoselectivity and
      excellent enantioselectivity.

PMID- 12227778
TI  - Synthesis and 12-helical secondary structure of beta-peptides containing (2R,3R)
      aminoproline.
AB  - [structure: see text] (2R,3R)-Aminoproline, a pyrrolidine-based beta-amino acid,
      was synthesized and incorporated into hexa-beta-peptide 4. This residue confers
      water solubility when the ring nitrogen is protonated and allows for 12-helix
      formation in aqueous solution. Circular dichroism spectra display the 12-helical
      signature, and 12-helical structure was confirmed by 2D NMR analysis.

PMID- 12227779
TI  - Development of a rapid, room-temperature dynamic kinetic resolution for efficient
      asymmetric synthesis of alpha-aryl amino acids.
AB  - [reaction: see text] A rapid, highly efficient and general dynamic kinetic
      resolution (DKR) of racemic alpha-aryl UNCAs with the dual-function catalysis of
      modified cinchona alkaloid was accomplished at room temperature. This DKR led to
      the development of a highly enantioselective catalytic method for the practical
      synthesis of a wide range of alpha-aryl and alpha-heteroaryl amino acids in 89
      92% ee and 86-95% yield from racemic UNCAs.

PMID- 12227780
TI  - Decarbopalladation of pi-allylpalladium intermediates formed from palladium
      catalyzed arylations of 3-allen-1-ols.
AB  - [reaction: see text] Unusual palladium-catalyzed arylative fragmentations of
      acyclic 3-allen-1-ols were observed. Oxidative addition of Pd(0) to aryl halides
      would form the arylpalladium halides, which added to the central carbon of
      allenes via carbopalladation to form the pi-allylpalladium intermediates. The pi
      allylpalladium intermediates would be reductively eliminated via carbon-carbon
      cleavage to give the arylated dienes and the alpha-hydroxyalkylpalladium
      intermediates, which were further reductively eliminated to the corresponding
      aldehydes.

PMID- 12227781
TI  - 6-Exo-spiro (alkoxycarbonylamino)methyl radical cyclization: highly regio- and
      stereoselective synthesis of (-)-sibirine.
AB  - [reaction: see text] The (methoxycarbonylamino)methyl radical can be readily
      generated from its PhSe precursor and undergoes preferential 6-exo-spiro
      cyclization when PhSO(2) is attached at the distal alkene carbon. This property
      was applied to the synthesis of the racemic and optically active spirocyclic
      alkaloid sibirine.

PMID- 12227782
TI  - Phenyliodonium zwitterion as an efficient electrophile in the palladium-catalyzed
      suzuki-type reaction: a novel method for the synthesis of 3-aryl-4
      hydroxycoumarins.
AB  - [reaction: see text] A palladium-catalyzed coupling reaction of phenyliodonium
      zwitterions with aryl boronic acids has been developed. The unique
      characteristics of the mild reaction conditions and convenient synthetic
      accessibility of phenyliodonium zwitterions make this method a valuable tool for
      generating diversified 3-aryl-4-hydroxycoumarins.

PMID- 12227786
TI  - "Chiral perturbation factor" approach reveals importance of entropy term in
      stereocontrol of the 2,4-pentanediol-tethered reaction.
AB  - The stereocontrol mechanism of the 2,4-pentanediol (PD)-tethered reaction was
      studied in detail using a reaction system consisting of phenyl and rhodium
      carbenoid moieties. Different tethers were examined to analyze the effects of the
      methyl groups on the PD tether. Among the reactions with these tethers, the PD
      tether achieves an unmeasurably high stereoselectivity in a diastereomeric ratio
      of >500. Another tether showing a high but measurable stereoselectivity in a
      ratio of 41 is mostly controlled by the entropy term. To clarify the role of the
      methyl groups on the chiral tethers, which are the origin of the stereocontrol,
      the "chiral perturbation factor" is introduced. This parameter is defined as the
      rate of a chiral reaction relative to that of an achiral reference reaction. By
      analyzing the temperature dependence of the chiral perturbation factors for
      different chiral-tethered reactions, high potentials of the PD-tethered reaction
      in its stereocontrol are concluded to be due to the entropy term.

PMID- 12227785
TI  - Amphidinolides H2-H5, G2, and G3, new cytotoxic 26- and 27-membered macrolides
      from dinoflagellate Amphidinium sp.
AB  - Six new macrolides, amphidinolides H2 (5), H3 (6), H4 (7), H5 (8), G2 (9), and G3
      (10), have been isolated from a marine dinoflagellate Amphidinium sp. (strain Y
      42). Cytotoxicity of five derivatives (11-15) of amphidinolide H (1) in addition
      to 10 amphidinolides (1-10) containing amphidinolides H (1), G (2), B (3), and D
      (4) was examined, and it was found that the presence of an allyl epoxide, an S
      cis-diene moiety, and the ketone at C-20 was important for the cytotoxicity of
      amphidinolide H (1)-type macrolides.

PMID- 12227787
TI  - Resurrection of neutral tris-homoaromaticity.
AB  - Neutral in-plane tris-homoaromaticity is evaluated in tris(bismethano)benzene
      (15) and modifications of this parent structure in which the pi-orbitals might
      interact in the plane established by the unsaturated carbon atoms (in-plane
      conjugation). On the basis of magnetic susceptibility exaltation, nucleus
      independent shift (NICS), and aromatic stabilization energy (ASE, evaluated via
      homodesmotic and isodesmic equations using B3LYP/6-311+G + ZPVE energies, as well
      as by MM3 and MM4 force field computations), we identified triene 17, a triply
      bridged analogue of 15, as the system where homoaromaticity is most effective.
      The NICS(total) in the center of 17 is -30.1 ppm and the diatropic pi
      contribution is -18.0 ppm. This structure possesses more than one-third of the
      aromatic stabilization of benzene and is the best candidate for neutral tris
      homoaromaticity ever proposed. The previously described tris-(bismethano)-benzene
      (15) also shows homoaromaticity but to a smaller extent compared to 17. Structure
      18, which is closely related to 17, also is significantly homoaromatic but, as
      evaluated by MM3, strain partially counteracts the stabilizing effects from
      homoconjugation. Such a counteracting increase in strain largely cancels or even
      overwhelms the stabilization from homoconjugation in all other species considered
      in this study.

PMID- 12227788
TI  - An efficient and large-scale enantioselective synthesis of PNP405: a purine
      nucleoside phosphorylase inhibitor.
AB  - An efficient and large-scale enantioselective synthesis of PNP405 (1), a purine
      nucleoside phosphorylase inhibitor, is described. This synthesis of 1 involved
      eight steps starting from o-fluorophenylacetic acid with a 21.6% overall yield
      and >99.5% enantiopurity. The key stereogenic center with (R)-configuration was
      created using Evans' asymmetric alkylation methodology. This synthesis also
      features the racemization-free reductive removal of the chiral auxiliary in 5
      using sodium borohydride, protection of the gamma-cyano alcohol 6 as the trityl
      ether by a new water-assisted tritylation with trityl chloride and triethylamine
      or with trityl alcohol and catalytic trifluoroacetic acid, and an efficient one
      pot cyclo-guanidinylation of 10 using cyanamide as the guanidinylating agent.

PMID- 12227789
TI  - Intramolecular reaction of a phenonium ion. Novel lactonization of 4-aryl-5
      tosyloxypentanoates and 4-aryl-5-tosyloxyhexanoates concomitant with a phenyl
      rearrangement.
AB  - The novel lactonizations of methyl 4-aryl-5-tosyloxypentanoate 1 and 4-aryl-5
      tosyloxyhexanoate 3 concomitant with a phenyl rearrangement are reported. The
      lactonizations were promoted by silica gel or heating in various solvents. By
      examining the effects of substituents of the aromatic ring on the reactivity, it
      was found that the reaction proceeded via a phenonium ion. This finding was
      supported by the stereochemical results for the lactonization of optical active
      1. Silica gel-promoted lactonization of 1 gave only gamma-lactone 2, whereas that
      of 3 afforded gamma-lactone 4 and delta-lactone 5. These lactonizations proved to
      be kinetically controlled. On the other hand, when 3c was heated in CH(3)NO(2) at
      70 degrees C, the highly selective formation of 4c was observed. Further detailed
      experiments confirmed that the thermal lactonization in CH(3)NO(2) was
      thermodynamically controlled.

PMID- 12227790
TI  - Carbonylation reactions of iodoarenes with PAMAM dendrimer-palladium catalysts
      immobilized on silica.
AB  - Palladium complexes immobilized onto generation 0-3 PAMAM dendrimers supported on
      silica were used as catalysts for the carbonylation of iodobenzene in methanol to
      form methyl benzoate. High yields were obtained and the catalyst was recycled 4-5
      times without significant loss of activity. The carbonylation reaction was found
      to be applicable to a variety of iodoarenes regardless of the nature of the
      substituent.

PMID- 12227791
TI  - Silver complexes with unsaturated thiacrown ethers: inclusion behavior of
      conformationally restricted macrocycles.
AB  - The reactions of 18- and 21-membered unsaturated thiacrown ethers, 18-UT-6 and 21
      UT-7, with CF(3)COOAg in acetone afforded novel silver(I) complexes Ag(I)(18-UT
      6)(CF(3)COO) and Ag(I)(2)(21-UT-7)(CF(3)COO)(2), respectively. The crystal
      structure of Ag(I)(18-UT-6)(CF(3)COO) shows that the silver atom occupies the
      cavity of the 18-UT-6 and the geometry around the silver atom has a distorted
      five-coordinate square pyramidal arrangement. The crystal structure of
      Ag(I)(2)(21-UT-7)(CF(3)COO)(2) shows that the two silver atoms and all sulfur
      atoms are nearly coplanar and the two trifluoroacetate groups are located at the
      opposite sides of the plane. The stoichiometry for the complexation of 15-UT-5,
      18-UT-6, and 21-UT-7 with CF(3)COOAg in solution was examined by (1)H NMR
      measurement. The titration plots of 15-UT-5 and 21-UT-7 show a distinct
      inflection point at 1:1 and 2:1 metal/macrocycle ratios, respectively, whereas
      the plot of 18-UT-6 gradually changes at the range of 1:1 to 2:1. From these
      results, 15-UT-5 and 21-UT-7 were found to show inclusion selectivity for number
      of silver ions, respectively, whereas 18-UT-6 showed low selectivity for the
      inclusion number of metals. Comparison of the oxidation and reduction potentials
      of the silver(I) complexes with those of free macrocycles and CF(3)COOAg revealed
      that unsaturated thiacrown ethers become difficult to be oxidized by complexation
      with CF(3)COOAg, and CF(3)COOAg becomes difficult to be reduced by complexation
      with unsaturated thiacrown ethers.

PMID- 12227792
TI  - Remote substituent effects on bond dissociation energies of para-substituted
      aromatic silanes.
AB  - UB3LYP/6-31G(d) and ROMP2/6-311++G(d,2p) methods were used to calculate the Si-X
      bond dissociation energies (BDEs) of a number of para-substituted aromatic
      silanes (4-Y-C(6)H(4)-SiH(2)X, where X = H, F, Cl, or Li). It was found that the
      substituent effect on the Si-H BDE of 4-Y-C(6)H(4)-SiH(3) was small, as the slope
      (rho(+)()) of the BDE- regression was only 0.09 kJ/mol. In comparison, the
      substituent effect on the Si-F BDE of 4-Y-C(6)H(4)-SiH(2)F was much stronger,
      whose rho(+ )()value was -2.34 kJ/mol. The substituent effect on the Si-Cl BDE of
      4-Y-C(6)H(4)-SiH(2)Cl was also found to be strong with a rho(+)() value of -1.70
      kJ/mol. However, the substituent effect on the Si-Li BDE of 4-Y-C(6)H(4)-SiH(2)Li
      was found to have a large and positive slope (+9.12 kJ/mol) against. The origin
      of the above remarkably different substituent effects on the Si-X BDEs was found
      to be associated with the ability of the substituent to stabilize or destabilize
      the starting material (4-Y-C(6)H(4)-SiH(2)X) as well as the product (4-Y-C(6)H(4)
      SiH(2)* radical) of the homolysis. Therefore, the direction and magnitude of the
      effects of Y-substituents on the Z-X BDEs in compounds such as 4-YC(6)H(4)Z-X
      should have some important dependence on the polarity of the Z-X bond undergoing
      homolysis. This conclusion was in agreement with that from earlier studies (for
      example, J. Am. Chem. Soc. 1991, 113, 9363). However, it indicated that the
      proposal from a recent work (J. Am. Chem. Soc. 2001, 123, 5518) was unfortunately
      not justified.

PMID- 12227793
TI  - Synthesis of a polymer-supported oxazolidine aldehyde for asymmetric chemistry.
AB  - An expedient synthesis of the polymer-supported aldehyde 3, as a Garner aldehyde
      equivalent, is described. Oxazolidine 3 may be obtained through preformation of
      aldehyde linker 4 in solution and loaded onto amine-terminating resin under
      peptide-coupling conditions, or alternatively via oxidation of polymer-bound
      alcohol 14. The integrity of the serine-derived stereocenter is maintained
      through all steps of the synthesis.

PMID- 12227794
TI  - Pentacoordinate phosphoranes with reversed apicophilicity as stable intermediates
      in a mitsunobu-type reaction.
AB  - Diisopropyl azodicarboxylate (DIAD) undergoes a cycloaddition reaction with the
      cyclic phosphites CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2)PX (1) [X = NCS (a), N(3) (b),
      Cl (c), NHMe (d) and Ph (e)] to afford the novel pentacoordinate phosphoranes 2a
      e as crystalline solids. This result is different from the reaction of PPh(3)
      with DIAD used in the well-known Mitsunobu reaction. X-ray crystallography of 2a,
      2b, and 2d reveals that the nitrogen, rather than the oxygen, occupies an apical
      position of the trigonal bipyramidal phosphorus. This is in violation of the
      commonly accepted preferences for substituents in trigonal bipyramidal
      phosphorus. In 2e, although the oxygen of the five-membered ring occupies the
      expected apical position, the phenyl group also occupies (the other) apical
      position, forcing the more electronegative oxygen atoms of the eight-membered
      ring to span equatorial-equatorial positions. In contrast to the above, the
      isocyanato compound CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2)PNCO (1f), upon treatment with
      DIAD, affords compound 3 to which a tetracoordinate structure is assigned.

PMID- 12227795
TI  - Linear synthesis of the tumor-associated carbohydrate antigens Globo-H, SSEA-3,
      and Gb3.
AB  - The tumor-associated carbohydrate antigens Globo-H, SSEA-3, and Gb3 were
      synthesized in a linear fashion using glycosyl phosphate monosaccharide building
      blocks. All of the building blocks were prepared from readily available common
      precursors. The difficult alpha-(1-->4-cis)-galactosidic linkage was installed
      using a galactosyl phosphate donor with high selectivity. Introduction of the
      beta-galactosamine unit required the screening a variety of amine protecting
      groups to ensure good donor reactivity and protecting group compatibility. An N
      trichloroacetyl-protected galactosamine donor performed best for the installation
      of the beta-glycosidic linkage. Conversion of the trichloroacetyl group to the N
      acetyl group was achieved under mild conditions, fully compatible with the
      presence of multiple glycosidic bonds. This synthetic strategy is expected to be
      amenable to the synthesis of the globo-series of tumor antigens on solid-support.

PMID- 12227796
TI  - Unusual sulfamate indoles and a novel indolo[3,2-a]carbazole from Ancorina sp.
AB  - Four new indoles, ancorinolates A-C and bis-ancorinolate B, which contain
      sulfamate and sulfate groups, were isolated from the aqueous extract of the
      sponge Ancorina sp. In addition, ancorinazole, an indolo[3,2-a]carbazole also
      possessing sulfamate and sulfate groups, was isolated from two separate New
      Zealand collections of Ancorina sp. Ancorinazole is the first indolo[3,2
      a]carbazole described as a natural product. Ancorinolates A (1) and C (3) showed
      weak HIV-inhibitory activity in the XTT-based, anticytopathicity assay.

PMID- 12227797
TI  - Novel stereoselective control over cis vs trans opening of benzo[c]phenanthrene
      3,4-diol 1,2-epoxides by the exocyclic N(2)-amino group of deoxyguanosine in the
      presence of hexafluoropropan-2-ol.
AB  - We describe a novel and efficient synthesis (62-84% yields) of the eight
      possible, diastereomerically pure, cis and trans, R and S O(6)-allyl-protected
      N(2)-dGuo phosphoramidite building blocks derived through cis and trans opening
      of (+/-)-3alpha,4beta-dihydroxy-1beta,2beta-epoxy-1,2,3,4
      tetrahydrobenzo[c]phenanthrene [BcPh DE-1 (1)] and (+/-)-3alpha,4beta-dihydroxy
      1alpha,2alpha-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene [BcPh DE-2 (2)] by
      hexafluoropropan-2-ol (HFP)-mediated addition of O(6)-allyl-3',5'-di-O-(tert
      butyldimethylsilyl)-2'-deoxyguanosine (3) at C-1 of the epoxides. Simply changing
      the relative amount of HFP used in the reaction mixture can achieve a wide ratio
      of cis/trans addition products. Thus, the observed cis/trans adduct ratio for the
      reaction of DE-1 (1) in the presence of 5 equiv of 3 varied from 17/83 to 91/9
      over the range of 5-532 equiv of HFP. The corresponding ratios for DE-2 (2)
      varied from 2/98 to 61/39 under the same set of conditions. When 1 or 2 was fused
      with a 20-fold excess of 3 at 140 degrees C in the absence of solvent HFP, almost
      exclusive trans addition (>95%) was observed for the both DEs. Through the use of
      varying amounts of HFP in the reaction mixture as described above, each of the
      eight possible phosphoramidite oligonucleotide building blocks (DE-1/DE-2,
      cis/trans, R/S) of the BcPh DE N(2)-dGuo adducts can be prepared in an efficient
      fashion. To rationalize the varying cis-to-trans ratio, we propose that the
      addition of 3 to 1 or 2 in the absence of solvent or in the presence of small
      amounts of HFP proceeds primarily via an S(N)2 mechanism to produce mainly trans
      opened adducts. In contrast, increasing amounts of HFP promote increased
      participation of an S(N)1 mechanism involving a relatively stable carbocation
      with two possible conformations. One of these conformations reacts with 3 to give
      mostly trans adduct, while the other conformation reacts with 3 to give mostly
      cis adduct.

PMID- 12227798
TI  - Asymmetric total syntheses of (+)-cheimonophyllon e and (+)-cheimonophyllal.
AB  - The highly enantiocontrolled total syntheses of natural (+)-cheimonophyllon E (5)
      and (+)-cheimonophyllal (6), biologically intriguing oxygenated bisabolane-type
      sesquiterpenoids, have been completed. The present synthetic strategy featured
      the use of an asymmetric aldol-type reaction for preparing in the first synthetic
      step an optically active 6-C-substituted 3-methyl-2-cyclohexenone derivative.
      Thus, a Mukaiyama aldol reaction of 1-methyl-3-silyloxy-1,3-cyclohexadiene 31
      with alpha,beta-unsaturated aldehyde 11 in the presence of a chiral
      (acyloxy)borane (CAB)-type Yamamoto catalyst 33 proceeded with high levels of
      both diastereo- and enantioselectivities. The predominant aldol adduct, syn-9,
      was transformed into gamma,delta-epoxy allylic alcohol 8 by a nine-step sequence,
      including the substrate-controlled 1,2-reduction of enone, syn-12, also the
      epoxidation of allylic alcohol 15. Epoxy-alcohol 8 underwent 5-exo-cyclization in
      a high regioselective manner under acidic conditions to produce a bicyclic key
      intermediate (+)-7, which was eventually efficiently converted to (+)
      cheimonophyllon E (5) or (+)-cheimonophyllal (6).

PMID- 12227799
TI  - Are 1,2-dihydrodiazetes aromatic? An experimental and computational
      investigation.
AB  - A thorough experimental and computational investigation of the aromaticity of the
      1,2-dihydrodiazete ring system was carried out. The X-ray crystal structure of
      1,2-dihydrodiazete 6 is reported, and the alkene-like reactivity of compound 6 is
      described. The compound's structure and reactivity suggest that 6 is not
      aromatic. This conclusion is corroborated by computational results on 6 and
      related compounds including homodesmotic reactions to test for aromatic
      stabilization, NICS calculations, and NBO calculations. Compound 6, and 1,2
      dihydrodiazetes in general, are concluded to be strained heterocycles with no
      indication for aromatic stabilization.

PMID- 12227800
TI  - Synthesis of new molecules containing head, spacer, and label moieties.
AB  - We describe the synthesis and characterization of novel molecules containing head
      with precise shape, spacer, and label moieties. The protocol is based on a Pd(0)
      catalyzed cross-coupling reaction between ethynylphenyl/bromide to obtain a rigid
      head followed by the attachment of a flexible spacer possessing two reactive
      functional groups on the termini. The final step consists of forming a covalent
      bond between spacer and label. In addition, monosubstituted soluble labels were
      synthesized in good yields.

PMID- 12227801
TI  - Convergent stereocontrol in peterson olefinations. Application to the synthesis
      of (+/-)-3-hydroxybakuchiol and corylifolin.
AB  - The iron-catalyzed Kirmse reaction was used to generate neopentyl alpha-silyl
      thioethers that were elaborated to meroterpenes using two complementary routes:
      one route involved a sila-Pummerer rearrangement, and the other route involved a
      Peterson olefination. While severe eclipsing interactions undermined the
      efficiency of the stereospecific sila-Pummerer rearrangement, they made it
      possible to stereoselectively generate E olefins without isolation or separation
      of syn- and anti-beta-silyl alkoxides. Addition of a neopentyl alpha-silyl
      alkyllithium intermediate to an aryl aldehyde generated a mixture of syn- and
      anti-beta-silyl alkoxides. The syn-beta-silyl alkoxide eliminated
      stereospecifically at -78 degrees C to give an E olefin, whereas the anti-beta
      silyl alkoxide was unreactive. The reaction mixture was then acidified and heated
      to induce stereospecific elimination of the anti isomer to give the same E olefin
      via a complementary cationic pathway. This route was used to complete the first
      synthesis of the meroterpene (+/-)-3-hydroxybakuchiol. In addition, we
      synthesized another meroterpene corresponding to the natural product corylifolin
      and offer evidence that the structure of corylifolin was misassigned.

PMID- 12227802
TI  - Oxovanadium complex-catalyzed aerobic oxidation of propargylic alcohols.
AB  - A catalytic system consisting of vanadium oxyacetylacetonate [VO(acac)(2)] and 3
      A molecular sieves (MS3A) in acetonitrile works effectively for the aerobic
      oxidation of propargylic alcohols [R(1)CH(OH)Ctbd1;CR(2)] to the corresponding
      carbonyl compounds under an atmospheric pressure of molecular oxygen. Although
      the reactivity of alpha-acetylenic alkanols (R(1) = alkyl) is lower compared to
      that of the alcohols of R(1) = aryl, alkenyl, and alkynyl, the use of VO(hfac)(2)
      as a catalyst and the addition of hexafluoroacetylacetone improve the product
      yield in these cases. A catalytic cycle involving a vanadium(V) alcoholate
      species and beta-hydrogen elimination from it has been proposed for this
      oxidation.

PMID- 12227803
TI  - Investigation of the enzymatic and nonenzymatic cope rearrangement of
      carbaprephenate to carbachorismate.
AB  - The dimethyl esters of carbaprephenate and 4-epi-carbaprephenate were prepared by
      modification of published procedures. In methanol these compounds are converted
      quantitatively to isomeric 6-hydroxytricyclo[3.3.1.0(2,7)]non-3-en-1,3-dimethyl
      esters via a two-step sequence involving an initial Cope rearrangement, followed
      by intramolecular Diels-Alder reaction of the dimethyl carbachorismate or 4-epi
      carbachorismate intermediates. Carbaprephenate and its epimer were obtained by
      alkaline hydrolysis of the corresponding dimethyl esters. These compounds, in
      contrast to their ester precursors, undergo spontaneous acid-catalyzed
      decarboxylation in aqueous solution. Only at high pH does the Cope rearrangement
      compete with decarboxylation. At pH 12 and 90 degrees C, carbaprephenate slowly
      rearranges to carbachorismate, which rapidly loses water to give 3-(2
      carboxyallyl)benzoic acid as the major product. A small amount of the
      intramolecular Diels-Alder adduct derived from carbachorismate is also observed
      by NMR as a minor product. Carbaprephenate is not a substrate for the enzyme
      chorismate mutase from Bacillus subtilis (BsCM), nor does carbaprephenate inhibit
      the normal chorismate mutase activity of this enzyme, even when present in 200
      fold excess over chorismate. Its low affinity for the enzyme-active site is
      presumably a consequence of placing a methylene group rather than an oxygen atom
      proximal to the essential cationic residue Arg90. Nevertheless, BsCM variants
      that lack this cation (R90G and R90A) do not accelerate the Cope rearrangement of
      carbaprephenate either, and a catalytic antibody 1F7, which exhibits modest
      chorismate mutase activity, is similarly inactive. Poor substrate binding and the
      relatively high barrier for the Cope compared to the Claisen rearrangement
      presumably account for the lack of detectable catalysis. Acceleration of this
      sigmatropic rearrangement apparently requires more than an active site that is
      complementary in shape to the reactive substrate conformer.

PMID- 12227804
TI  - Solid-phase synthesis of 4(1H)-quinolone and pyrimidine derivatives based on a
      new scaffold-polymer-bound cyclic malonic acid ester.
AB  - An efficient method for the preparation of polymer-bound cyclic malonic acid
      ester starting from Merrifield resin has been developed. Reaction of the resin
      bound cyclic malonic acid ester with triethyl orthoformate and subsequent double
      substitution with nucleophilic reagents, such as arylamine, urea, thiourea, 2
      aminobenzothiazoles, or isothiosemicarbazones, afforded the corresponding polymer
      bound substituted aminomethylene cyclic malonic acid esters, which upon thermal
      treament led to 4(1H)-quinolones, 3-substituted uracils and thiouracils, 4H
      pyrimido[2,1-b]benzothiazol-4-ones, and 1-(N-alkylidene or benzylideneamino)-1,6
      dihydro-2-methylthio-6-oxo-pyrimidines, depending on the structures of the
      nucleophilic reagents.

PMID- 12227805
TI  - Unusual reaction of 2-(trifluoromethyl)-1,2-dihydro-3lambda(6)-thieno- [2,3
      c]chromen-3,3,4-triones with hydrazine as a new route to 3-hydrazinopyridazine
      derivatives.
AB  - Oxidation of 2-(trifluoromethyl)-1,2-dihydro-4H-thieno[2,3-c]chromen-4-ones 2
      with H(2)O(2) in AcOH gives 2-(trifluoromethyl)-1,2-dihydrothieno[2,3-c]chromen
      3,3,4-triones 3, which are transformed into 3-hydrazinopyridazine derivatives 4
      in high yields by treatment with hydrazine hydrate in ethanol.

PMID- 12227806
TI  - Practical asymmetric synthesis of aprepitant, a potent human NK-1 receptor
      antagonist, via a stereoselective Lewis acid-catalyzed trans acetalization
      reaction.
AB  - A streamlined and high-yielding synthesis of aprepitant (1), a potent substance P
      (SP) receptor antagonist, is described. The enantiopure oxazinone 16 starting
      material was synthesized via a novel crystallization-induced dynamic resolution
      process. Conversion of 16 to the penultimate intermediate cis-sec-amine 9
      features a highly stereoselective Lewis acid-catalyzed trans acetalization of
      chiral alcohol 3 with trichloroacetimidate 18 followed by inversion of the
      adjacent chiral center on the morpholine ring. The six-step process for the
      synthesis of 9 was accomplished in extremely high overall yield (81%) and with
      only two isolations.

PMID- 12227807
TI  - Chemistry of bifunctional photoprobes. 6. Synthesis and characterization of high
      specific activity metalated photochemical probes: development of novel rhenium
      photoconjugates of human serum albumin and fab fragments.
AB  - Functionalization of perfluoro aryl azides by bifunctional chelating agents
      (BFCAs) capable of forming high specific activity complexes with (99m)Tc (for
      gamma-imaging) and (188)Re (for radiotherapy) is described. The synthesis of
      multidonor BFCAs containing N(2)S(2), N(4), and N(3)S donor groups containing
      imidazole, pyridine, and pyrazine functionalities that may be important for
      tuning the pharmacokinetic parameters is also described. Functionalization of
      perfluoro aryl azides at various sites on BFCAs yields novel bifunctional
      photolabile chelating agents (BFPCAs) that are useful for covalent attachment to
      biomolecules. A representative Re-BFPCA 8a in a model solvent, diethylamine,
      proceeded to give a high yield of intermolecular NH insertion product without the
      decomplexation of the metal ion from 8a. All products originated from the
      photolysis of 8a in diethylamine are characterized by analytical techniques, and
      a plausible mechanism of formation of different photolytic products is suggested.
      The high yield of intermolecular NH insertion of Re-BFPCA 8a is extended to
      labeling of human serum albumin (HSA) and Fab fragments under aqueous conditions.
      The photolabeling technology developed here offers a new way to attach
      diagnostically and therapeutically useful radiotracers (e.g., (99m)Tc, (188)Re)
      to Fab fragments for potential noninvasive imaging and therapy of cancer.

PMID- 12227808
TI  - A new synthesis of Neu5Ac from D-glucono-delta-lactone.
AB  - A new route to Neu5Ac methyl ester (23) with a readily available sugar D-glucono
      delta-lactone as starting material has been developed. A diastereoselective
      propargylation of alpha-acetamino aldehyde and a subsequent KMnO(4) oxidation of
      the terminal alkyne served as the key steps.

PMID- 12227809
TI  - Synthesis of [3,4-(13)c(2)]-enriched bile salts as NMR probes of protein-ligand
      interactions.
AB  - Synthetic methodology that allows for incorporation of isotopic carbon at the C-3
      and C-4 positions of bile salts is reported. Three [3,4-(13)C(2)]-enriched bile
      salts were synthesized from either deoxycholic or lithocholic acid. The steroid
      3alpha-OH group was oxidized and the A-ring was converted into the Delta(4)-3
      ketone. The C-24 carboxylic acid was next converted into the carbonate group and
      selectively reduced to the alcohol in the presence of the A-ring enone. Following
      protection of the 24-OH group, the Delta(4)-3-ketone was converted into the A
      ring enol lactone. Condensation of the enol lactone with [1,2-(13)C(2)]-enriched
      acetyl chloride and subsequent Robinson annulation afforded a [3,4-(13)C(2)]
      enriched Delta(4)-3-ketone that was subsequently converted back into a 3alpha
      hydroxy-5beta-reduced bile steroid. C-7 hydroxylation, when necessary, was
      achieved via conversion of the Delta(4)-3-ketone into the corresponding
      Delta(4,6)-dien-3-one, epoxidation of the Delta(6)-double bond, and
      hydrogenolysis/hydrogenation of the 5,6-epoxy enone system. The [3,4-(13)C(2)]
      enriched bile salts were subsequently complexed to human ileal bile acid binding
      protein (I-BABP), and (1)H-(13)C HSQC spectra were recorded to show the utility
      of the compounds for investigating the interactions of bile acids with I-BABP.

PMID- 12227810
TI  - A novel strategy for the synthesis of benzofuran skeleton neolignans: application
      to ailanthoidol, XH-14, and obovaten.
AB  - A convenient and general approach to the synthesis of the benzofuran skeleton
      compounds ailanthoidol, XH-14, and obovaten was developed. Starting from
      vanillin, a series of reactions afforded 7 in 71% yield. Treatment of 7 with n
      BuLi followed by addition of substituted benzaldehydes resulted in the formation
      of carbinols 11 and 31. The substituted benzophenones obtained from oxidation of
      11 and 31 were treated with trimethylsilyldiazomethane lithium salt to give
      diphenylacetylenes 15 and 33, respectively. 15 and 33 were then cyclized in the
      presence of either mercury acetate in acetic acid or bromine in chloroform to
      give 3-chloromercurio- or 3-bromobenzofuran, respectively. The 3-chloromercurio
      intermediates could be reduced to proton or derivatized to ester or bromide,
      leading to the synthesis of ailanthoidol, XH-14, and obovaten, respectively. In
      addition, necleophilic substitution was used to introduce a formyl or methyl
      group into the 3-bromobenzofuran derivatives, providing an alternative pathway to
      XH-14 and obovaten. The final elongation and deprotection reaction furnished the
      desired ailanthoidol, XH-14, and obovaten in yields of 30, 15, and 11%,
      respectively.

PMID- 12227811
TI  - Nucleic acid related compounds. 116. Nonaqueous diazotization of aminopurine
      nucleosides. Mechanistic considerations and efficient procedures with tert-butyl
      nitrite or sodium nitrite.
AB  - Nonaqueous diazotization-dediazoniation of two types of aminopurine nucleoside
      derivatives has been investigated. Treatment of 9-(2,3,5-tri-O-acetyl-beta-D
      ribofuranosyl)-2-amino-6-chloropurine (1) with SbCl(3)/CH(2)Cl(2) was examined
      with benzyltriethylammonium (BTEA) chloride as a soluble halide source and tert
      butyl nitrite (TBN) or sodium nitrite as the diazotization reagent. Optimized
      yields (>80%) of the 2,6-dichloropurine derivative were obtained with SbCl(3).
      Combinations with SbBr(3)/CH(2)Br(2) gave the 2-bromo-6-chloropurine product
      (>60%), and SbI(3)/CH(2)I(2)/THF gave the 2-iodo-6-chloropurine derivative
      (>45%). Antimony trihalide catalysis was highly beneficial. Mixed combinations
      (SbX(3)/CH(2)X'(2); X/X' = Br/Cl) gave mixtures of 2-(bromo, chloro, and hydro)-6
      chloropurine derivatives that were dependent on reaction conditions. Addition of
      iodoacetic acid (IAA) resulted in diversion of purine radical species into a 2
      iodo-6-chloropurine derivative with commensurate loss of other radical-derived
      products. This allowed evaluation of the efficiency of SbX(3)-promoted cation
      derived dediazoniations relative to radical-derived reactions. Efficient
      conversions of adenosine, 2'-deoxyadenosine, and related adenine nucleosides into
      6-halopurine derivatives of current interest were developed with analogous
      combinations.

PMID- 12227812
TI  - Enantioselective synthesis of 2-substituted 2-phenylethylamines by lithiation
      substitution sequences: synthetic development and mechanistic pathway.
AB  - The lithiation and asymmetric substitution of N-(2-phenylethyl)isobutyramide (2)
      with selected electrophiles, under the influence of (-)-sparteine, provides
      benzylically substituted products in 58-90% yields with enantiomeric ratios (ers)
      from 72:28 to 91:9. Syntheses of enantioenriched dihydroisoquinolines (S)-18 and
      (S)-19 and a tetrahydroisoquinoline (4S)-20 provide examples of synthetic
      applications. Mechanistic investigations suggest the enantiodetermining step at 
      78 degrees C is a dynamic thermodynamic resolution.

PMID- 12227813
TI  - Synthesis and structure of a stabilized 10-membered cyclic enediyne.
AB  - The synthesis and structure of an acetal protected 10-membered cyclic enediyne
      1,2-diol rac-10 is reported. The conformational constrain of the unsaturated
      macrocycle by the acetal protection group prevents the thermal cyclization
      reaction of the endiyne during synthesis and purification.

PMID- 12227814
TI  - Synthesis and properties of a new member of the calixnaphthalene family: a C(2)
      symmetrical endo-calix[4]naphthalene.
AB  - The synthesis of a new endo-calix[4]naphthalene is described. The reaction
      sequence involves the cyclocondensation of a key bisnaphthylmethane intermediate
      (8) with formaldehyde. This key intermediate (8) is formed using a modified
      Suzuki-Miyaura Pd-catalyzed cross-coupling reaction between bromomethylnaphthyl
      (6) and naphthylboronic acid (7), both of which can be derived from 2
      hydroxynaphthoic acid.

PMID- 12227815
TI  - Synthesis of the C1'-C11' oxazole-containing side chain of leucascandrolide A.
      Application of a Sonogashira cross-coupling.
AB  - An efficient, convergent synthesis of the C1'-C11' side chain (3) of
      leucascandrolide A (1) has been achieved. The key bond connection is made through
      the use of a palladium(0)-catalyzed Sonogashira cross-coupling between trifloyl
      oxazole (4) and alkynylmetal species (5).

PMID- 12227816
TI  - Dynamic kinetic resolution of 2-oxocycloalkanecarbonitriles: chemoenzymatic
      syntheses of optically active yclic beta- and gamma-amino alcohols.
AB  - A series of fungi and yeasts have been tested for the stereoselective
      bioreduction of 2-oxocycloalkanecarbonitriles, 1. The yeast Saccharomyces
      montanus CBS 6772 yielded the corresponding cis-hydroxy nitriles, 2, in >90% ee
      and de and in high chemical yields. Through simple and efficient procedures, they
      were transformed into optically active 2-amino and 2-aminomethyl cycloalkanols.

PMID- 12227817
TI  - Nanosecond generation of tyrosyl radicals via laser-initiated decaging of oxalate
      modified amino acids.
AB  - We describe a general method for the unimolecular photochemical generation of
      tyrosyl radicals from a diaryl oxalate ester platform on the nanosecond time
      scale. Symmetric and asymmetric tyrosine oxalate esters have been prepared in
      gram quantities. Direct photocleavage of the oxalate linkage by laser flash
      photolysis affords tyrosyl radicals within 50 ns. This approach provides
      unnatural caged amino acids that may be incorporated into model and biological
      systems for the study of proton-coupled electron transfer in enzymatic catalysis.

PMID- 12227818
TI  - Influence of diene substitution on transition state stabilization in Diels-Alder
      reaction.
AB  - A theoretical analysis of transition state stabilization in D-A reactions of
      substituted dienes according to the nature and position of the substituent has
      been carried on. Results revealed that substituents (de)stabilize TS through four
      effects (steric, mesomeric, inductive, and polarizability) acting principally by
      favoring the electronic transfer between the two partners. The correlations
      observed point out nevertheless that the reactivity of substituted dienes in [4 +
      2] cycloadditions on ethylene may principally be predicted by the sole use of the
      F + R electronic parameters.

PMID- 12227819
TI  - Formation of dimer-type ketals in the reaction of 2,4,6-trichlorophenol and 2,4,6
      trichloro-m-cresol with calcium hypochlorite in methanol: conversion to quinones
      and other compounds.
AB  - 2,4,6-Trichlorophenol (2) and 2,4,6-trichloro-m-cresol (5) react with calcium
      hypochlorite (Ca(OCl)(2)) in MeOH to give respectively dimer-type ketals 2
      (2',4',6'-trichlorophenoxy)-4,4-dimethoxy-6-chlorocyclohexadien-2,5-one (6) and 2
      (3'-methyl-2',4',6'-trichlorophenoxy)-4,4-dimethoxy-5-methyl-6
      chlorocyclohexadien-2,5-one (7). Ketal 6, which was too unstable to be isolated,
      and 7 hydrolyzed in H(2)O/HCl to 2-(2',4',6'-trichlorophenoxy)-6-chloro-1,4
      benzoquinone (8) and 2-(3'-methyl-2',4',6'-trichlorophenoxy)-5-methyl-6-chloro
      1,4-benzoquinone (9), respectively. Ketal 6 and quinone 8 were also produced when
      2 and Ca(OCl)(2) reacted in DMF, followed by addition of MeOH and H(2)O,
      respectively. The mechanisms of these reactions are examined. Conversion of the
      ketals and quinones to other products is described.

PMID- 12227820
TI  - The thermal reaction of sterically hindered nitroxyl radicals with allylic and
      benzylic substrates: experimental and computational evidence for divergent
      mechanisms.
AB  - The reaction of stable sterically hindered nitroxyl radicals with benzylic and
      allylic substrates was investigated. An allyloxyamine derivative was obtained by
      the reaction of 2 molar equiv of a nitroxyl radical with an unactivated alkene.
      Experimental and computational evidence is consistent with a low-energy pathway
      involving addition of the nitroxyl radical to the double bond followed by H-atom
      abstraction from the intermediate by another equivalent of nitroxyl radical.

PMID- 12227821
TI  - Corticosteroid decomposition via a mixed anhydride.
AB  - Oxidation of dexamethasone in an aqueous suspension by air during prolonged
      storage produces the 17alpha-formyloxy-17beta-carboxylic acid 4. A pathway to 4
      is proposed that involves Baeyer-Villiger-type oxidation of keto aldehyde 1 to
      mixed anhydride 5, followed by intramolecular formyl transfer. Synthetically,
      acid 3 was reacted with N,N'-carbonyldiimidazole followed by triethylammonium
      formate in order to generate the transient anhydride 5 en route to an authentic
      sample of 4.

PMID- 12227822
TI  - An efficient synthesis of novel carbocyclic nucleosides with use of ring-closing
      metathesis from D-lactose.
AB  - This paper describes an efficient synthetic route for various types of novel
      carbocyclic nucleosides. The required stereochemistry of the targeted nucleosides
      was successfully obtained with use of Grubbs cyclization and Trost allylic
      alkylation from the carbohydrate chiral template "D-lactose".

PMID- 12227823
TI  - Bulky trialkylsilyl acetylenes in the Cadiot-Chodkiewicz cross-coupling reaction.
AB  - Bulky trialkylsilyl-protected alkynes such as triethylsilyl (TES), tert
      butyldimethylsilyl (TBS), and triisopropylsilyl (TIPS) acetylenes underwent the
      Cadiot-Chodkiewicz cross-coupling reaction with different bromoalkynes to form a
      variety of synthetically useful unsymmetrical diynes in good yields. The diyne
      alcohol 10 was transformed regio- and stereoselectively into enynes by
      hydrotelluration, carbometalation, and reduction reactions.

PMID- 12227824
TI  - Ionic liquid-coated enzyme for biocatalysis in organic solvent.
AB  - Ionic liquid-coated enzyme (ILCE) is described as a useful catalyst for
      biocatalysis in organic solvent. An ionic liquid, [PPMIM]-[PF(6)] (1, [PPMIM] = 1
      (3'-phenylpropyl)-3-methylimidazolium), which is solid at room temperature and
      becomes liquid above 53 degrees C, was synthesized in two steps from N
      methylimidazole. The coating of enzyme was done by simply mixing commercially
      available enzyme with 1 in the liquid phase above 53 degrees C and then allowing
      the mixture to cool. A representative ILCE, prepared with a lipase from
      Pseudomonas cepacia, showed markedly enhanced enantioselectivity without losing
      any significant activity.

PMID- 12227826
TI  - Highly stereoselective C-allylation of an enantiopure alpha-sulfinyl
      thioacetamide.
AB  - The alkylation of the lithium enolate of enantiopure alpha-cyclohexylsulfinyl
      thioacetamide 1 with allyl bromides 5 possessing an electron-withdrawing group at
      the vinylic position does not occur at the sulfur center - as expected in the
      sulfur series - but at the carbon center through conjugate addition followed by
      bromide elimination. The modest to excellent 1,2-asymmetric induction achieved by
      the alkylsulfinyl group (dr up to 100:0) is explained by an electronic model.

PMID- 12227825
TI  - Synthetic approach to analogues of the original structure of sclerophytin A.
AB  - A route to analogues of the original structure of sclerophytin A is described.
      The beta-anomer of dideoxyribosyl nitriles 10a,b (prepared from glutamic acid)
      was converted into the methyl ketone 11. Addition of a silylated acetylide to 11
      in diethyl ether/trimethylamine gave mainly 22a. Alkylation with methallyl halide
      and ozonolysis gave the ketone 24, which was then converted by hydrogenation and
      a second ozonolysis into the keto aldehyde 26. A two-step aldol process afforded
      the desired 3-pyrone 27 in good overall yield. However, several methods for the
      conversion of this enone 27 into the desired sclerophytin analogue 2 failed.

PMID- 12227827
TI  - Convergent synthesis of isomeric pairs of metallocene-containing polyether
      macrocycles.
AB  - A general method for rapid construction of metallocene-based hosts is described.
      Treatment of polyether bridged bis(diphenylacetylenes) with a source of
      cyclopentadienyl cobalt at high temperature leads, via macrocyclization and
      capture of the intermediate cyclobutadiene, to macrocyclic systems tethered to an
      integral metallocene platform. Equal yields of the two possible structural
      isomers, the products of parallel or antiparallel cycloaddition of the precursor,
      are obtained. A combination of X-ray crystallography and NMR is employed to
      assign structures to the individual isomers and to assess the strength of lithium
      ion binding by the individual macrocycles.

PMID- 12227828
TI  - Norbornadiene as an efficient hydrogen scavenger for the palladium-catalyzed
      conversion of hydrosilanes to alkoxysilanes.
AB  - A palladium-catalyzed mild and efficient method for the alcoholysis of
      hydrosilanes containing a C=C bond in the presence of norbornadiene (NBD) is
      reported. The highly strained NBD acts as a hydrogen scavenger, which abstracts
      the hydrogen produced during the process, protecting the C=C bond from being
      hydrogenated.

PMID- 12227829
TI  - Impaired trafficking of human kidney anion exchanger (kAE1) caused by hetero
      oligomer formation with a truncated mutant associated with distal renal tubular
      acidosis.
AB  - Autosomal dominant distal renal tubular acidosis (dRTA) has been associated with
      several mutations in the anion exchanger AE1 gene. The effect of an 11-amino-acid
      C-terminal dRTA truncation mutation (901 stop) on the expression of kidney AE1
      (kAE1) and erythroid AE1 was examined in transiently transfected HEK-293 cells.
      Unlike the wild-type proteins, kAE1 901 stop and AE1 901 stop mutants exhibited
      impaired trafficking from the endoplasmic reticulum to the plasma membrane as
      determined by immunolocalization, cell-surface biotinylation, oligosaccharide
      processing and pulse-chase experiments. The 901 stop mutants were able to bind to
      an inhibitor affinity resin, suggesting that these mutant membrane proteins were
      not grossly misfolded. Co-expression of wild-type and mutant kAE1 or AE1 resulted
      in intracellular retention of the wild-type proteins in a pre-medial Golgi
      compartment. This dominant negative effect was due to hetero-oligomer formation
      of the mutant and wild-type proteins. Intracellular retention of kAE1 in the
      alpha-intercalated cells of the kidney would account for the impaired acid
      secretion into the urine characteristic of dRTA.

PMID- 12227830
TI  - Restoration of high-level transport activity by human reduced folate
      carrier/ThTr1 thiamine transporter chimaeras: role of the transmembrane domain
      6/7 linker region in reduced folate carrier function.
AB  - The reduced folate carrier (RFC; SLC19A1) is closely related to the thiamine
      transporter, SLC19A2 (ThTr1). Hydropathy models for these homologous transporters
      predict up to 12 transmembrane domains (TMDs), with internally oriented N- and C
      termini and a large central loop between TMDs 6 and 7. The homologies are
      localized mostly in the TMDs. However, there is little similarity in their N- and
      C-terminal domains and the central peptide linkers connecting putative TMDs 1-6
      and TMDs 7-12. To explore the functional role of the 61-amino acid central linker
      in the human RFC (hRFC), we introduced deletions of 49 and 60 amino acids into
      this region, differing by the presence of a stretch of 11 highly conserved amino
      acids between the human and rodent RFCs (positions 204-214). An additional hRFC
      construct was prepared in which only the 11 conserved amino acids were deleted.
      The resulting hRFC(D215-R263 Delta), hRFC(K204-R263 Delta) and hRFC(K204-R214
      Delta) proteins were transfected into transport-impaired K562 cells. The deletion
      constructs were all expressed in plasma membranes; however, they were completely
      inactive for methotrexate and (6 S )5-formyl tetrahydrofolate transport.
      Insertion of non-homologous 73- and 84-amino acid fragments from the structurally
      analogous ThTr1 linker region into position 204 of hRFC(K204-R263 Delta) restored
      low levels of transport (16-21% of the wild type). Insertion of the ThTr1 linkers
      into hRFC(D215-R263 Delta) at position 215 restored 60-80% of wild-type levels of
      transport. Collectively, our results suggest that the role of the hRFC linker
      peptide is to provide the proper spatial orientation between the two halves of
      the hRFC protein for optimal function, and that this is largely independent of
      amino acid sequence. Our results also demonstrate a critical transport role for
      the stretch of 11 conserved amino acids starting at position 204 of hRFC.

PMID- 12227831
TI  - Construction and high cytoplasmic expression of a tumoricidal single-chain
      antibody against hepatocellular carcinoma.
AB  - BACKGROUND: Hep27 monoclonal (Hep27 Mab) is an antibody against hepatocellular
      carcinoma. Hep27 Mab itself can inhibit the growth of a hepatocellular carcinoma
      cell line (HCC-S102). We attempted to produce a single-chain fragment (scFv), a
      small fragment containing an antigen-binding site of Hep27 Mab, by using DNA
      recombinant techniques. RESULTS: The sequences encoding the variable regions of
      heavy (VH) and light (VL) chains of a murine Hep27 Mab were linked together by a
      linker peptide (Gly4Ser)3 and tagged with a hexa-histidine at the C-terminal; the
      resultant DNA construct was expressed in E. coli as an insoluble protein. The
      denatured scFv was refolded and purified by immobilized metal ion affinity
      chromatography (12 mg/l with a molecular weight of 27 kDa). Hep27scFv exhibited a
      tumoricidal activity against the HCC-S102 cell as its parental antibody (Hep27
      Mab). CONCLUSION: This scFv may be a potential candidate for a targeting agent in
      HCC immunodiagnosis or immunotherapy.

PMID- 12227832
TI  - Prevalence of attention deficit/hyperactivity disorder among adults in obesity
      treatment.
AB  - BACKGROUND: Bariatric patients showing poor "focus" during treatment more often
      failed to lose weight or maintain reduced weight. Evaluation of these patients
      identified a number having attention deficit/hyperactivity disorder (ADHD),
      evidently a potent factor limiting successful weight control. After searches
      found no published reports describing comorbid ADHD and obesity, this report was
      conceived to begin exploring the prevalence and characteristics of these
      patients. METHOD: Clinical records of 215 patients receiving obesity treatment
      during 2000 were reviewed. Data collected and analyzed included age, sex,
      beginning and ending body mass index (BMI), number of clinic visits, months of
      treatment, and diagnostic category (ADHD, some ADHD symptoms, non-ADHD). DSM-IV
      criteria were used, except age of onset was modified to <= 12 years. RESULTS:
      Whole sample ADHD prevalence was 27.4% (CI:21.1,32.9), but 42.6% (CI: 36.3% to
      48.9%) for BMI >= 40. Mean weight loss among obese patients with ADHD (OB+ADHD)
      was 2.6 BMI (kg/m2) vs. 4.0 for non-ADHD (NAD) (p < 0.002). For BMI >= 40,
      OB+ADHD had BMI loss 2.9 vs. 7.0 (NAD) (p < 0.004). OB+ADHD had more clinic
      visits, with a trend toward longer treatment duration. CONCLUSIONS: ADHD was
      highly prevalent among obese patients and highest in those with extreme obesity.
      Comorbid obesity and ADHD symptoms rendered treatment less successful compared to
      NAD counterparts. Reasons for the comorbidity are unknown, but may involve brain
      dopamine or insulin receptor activity. If replicated in further studies, these
      findings have important implications for treatment of severe and extreme obesity.

PMID- 12227834
TI  - Eating crow while it's still warm.

PMID- 12227835
TI  - Home: is it different or is it better?

PMID- 12227833
TI  - Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive
      impairment.
AB  - BACKGROUND: Mild cognitive impairment (MCI) was recently described as a
      heterogeneous group with a variety of clinical outcomes and high risk to develop
      Alzheimer's disease (AD). Regional cerebral blood flow (rCBF) as measured by
      single photon emission computed tomography (SPECT) was used to study the
      heterogeneity of MCI and to look for predictors of future development of AD.
      METHODS: rCBF was investigated in 54 MCI subjects using Tc-99m
      hexamethylpropyleneamine oxime (HMPAO). An automated analysis software (BRASS)
      was applied to analyze the relative blood flow (cerebellar ratios) of 24 cortical
      regions. After the baseline examination, the subjects were followed clinically
      for an average of two years. 17 subjects progressed to Alzheimer's disease (PMCI)
      and 37 subjects remained stable (SMCI). The baseline SPECT ratio values were
      compared between PMCI and SMCI. Receiver operating characteristic (ROC) analysis
      was applied for the discrimination of the two subgroups at baseline. RESULTS: The
      conversion rate of MCI to AD was 13.7% per year. PMCI had a significantly
      decreased rCBF in the left posterior cingulate cortex, as compared to SMCI. Left
      posterior cingulate rCBF ratios were entered into a logistic regression model for
      ROC curve calculation. The area under the ROC curve was 74%-76%, which indicates
      an acceptable discrimination between PMCI and SMCI at baseline. CONCLUSION: A
      reduced relative blood flow of the posterior cingulate gyrus could be found at
      least two years before the patients met the clinical diagnostic criteria of AD.

PMID- 12227836
TI  - Qualitative evaluation of a stress management intervention for elderly caregivers
      at home: a constructivist approach.
AB  - The purpose of this project was to evaluate, using a constructivist qualitative
      design, an individual stress management intervention based on a stress-coping
      model and intended for family caregivers of elderly persons within the current
      context of the shift to ambulatory care. This nursing intervention comprised
      seven weekly encounters with caregivers following their elderly family member's
      discharge from hospital and a follow-up visit one month after. The aim of the
      qualitative evaluation was to document the feasibility and acceptability of the
      content of the intervention, its relevance in terms of process and structure, and
      the benefits to the principal stakeholders. This action research project was a
      case study of four participants. The assessment instruments included an
      intervention analysis grid, a diary, and a semistructured interview guide with
      the participants. Data analysis drew on Guba and Lincoln's (1989) method which
      made it possible to refine the intervention. Results underscored that certain
      implementation conditions must be respected in order to ensure the intervention's
      acceptability and feasibility. Above all, it must remain flexible and the nurse
      must possess the requisite clinical skills and theoretical knowledge. It is
      important also to screen judiciously for caregivers likely to benefit from the
      intervention. The pertinence of using a circular intervention model rather than a
      linear approach to stress management was highlighted as well.

PMID- 12227838
TI  - Elites and popular nationalism.
AB  - Much current theory concerning nationalism holds that elites commonly create or
      cause popular nationalism. In part, that thesis may be due to an overwhelming
      emphasis in research on nationalism on positive cases: cases where nationalism
      has appeared, ignoring cases where it has not. In this article, I challenge the
      thesis by showing numerous historical cases in which elites have promoted
      nationalisms that ordinary people have not adopted, or in which ordinary people
      have adopted a nationalism before it was taken up by elites. Even if elites do
      not create popular nationalism, however, they can and do shape its expression in
      a variety of ways, such as organizing it, providing relevant information, or
      providing opportunity or incentive for it. I show this through historical
      examples.

PMID- 12227837
TI  - Contextual analysis of coping: implications for immigrants' mental health care.
AB  - Providing high quality and effective health care services that are culturally
      acceptable and appropriate to clients has become an important issue for many
      health care providers. This paper explores problems associated with the
      traditional model that views coping according to hierarchical style and traits.
      While some scholars who have adopted this theoretical framework have made many
      contributions to the development of stress and coping theories, limitations are
      present. Using Vietnamese immigrants' experiences as examples, I argue that
      coping theories should emphasize the contextual nature of stress and coping, and
      that coping should be viewed as a dynamic process that varies under different
      social, cultural, political, economic, and historical conditions. Drawing from
      the work of others on coping, culture, imperialism, and colonialism, I explore
      the way that certain cultural conceptualizations determine how individuals cope.
      An understanding of the contextual nature of coping and of a Vietnamese
      immigrant's experience of coping with stressors and illness has implications for
      mental health care practice and research.

PMID- 12227839
TI  - Interpersonal trust and voluntary associations: examining three approaches.
AB  - The relationship between interpersonal trust and membership in voluntary
      associations is a persistent research finding in sociology. What is more, the
      notion of trust has become a central issue in current social science theorizing
      covering such diverse approaches as transaction costs economics or cognitive
      sociology. In different ways and for different purposes, these approaches address
      the role of voluntary organizations, although, as this paper argues, much of this
      thinking remains sketchy and underdeveloped. Against an empirical portrait of
      this relationship, the purpose of this paper is to assess such theorizing. We
      first set out to explicate major approaches to trust in economics, sociology and
      political science, using the non-profit or voluntary organization as a focal
      point. We then examine the various approaches in terms of their strengths and
      weaknesses, and, finally, identify key areas for theoretical development. In
      particular, we point to the social movement literature, the social psychology of
      trust, and recent thinking about civil society.

PMID- 12227840
TI  - Graduate density, gender, and employment.
AB  - The expansion of higher education is often viewed as reflecting increased demand
      for skills, whether related to technological change or the growing complexity of
      the economy. It is also linked to widening pay differentials between the poorly
      and highly educated. There are reasons, however, to question these associations.
      Even if demand for graduates is growing the supply of graduates might as a result
      of the status derived from having a degree still exceed this. The demand for
      graduates itself need not be wholly tied in with upgrading of the labour force.
      Graduates could be part of a more flexible workforce who increasingly undertake
      non-graduate work, thus downgrading their labour-market position. LFS (Labour
      Force Survey) and BHPS (British Household Panel Study) data are used to show that
      there has been no major shift in the distribution of graduates in the British
      labour market, that career starts are increasingly at a lower status point, and
      that there is a negative effect of graduate density on wages. There are also
      redistributional effects. There has been a large increase in the social demand
      for higher education by women, and they have gained from this expansion while men
      have lost out. In addition, graduate density is positive for non-graduates, who
      gain from the reduced rewards accruing to graduates. The results call into
      question the simple idea of a trend towards a demand for increasing levels of
      skills and qualifications. More attention should be paid to the distribution of
      skills and to complex interactions within this.

PMID- 12227841
TI  - Weberian perspectives on science, technology and the economy.
AB  - Several disciplines have contributed to the understanding of the relationship
      between science, technology, and economic change. Weber's perspective on this
      relationship, however, has not been properly explored. In the first part of this
      paper, we give an account of Weber's perspective. In the second part, we
      critically assess Weber's ideas, indicating those that are useful and those that
      deserve to be abandoned. We also confront a revised Weberian perspective with
      those of the main contemporary competitors, the key ideas of economists and
      economic historians on one side and social constructivists on the other. We
      conclude that a Weberian comparative-historical approach compares favourably with
      these competitors, and suggest where his approach still requires further work.

PMID- 12227842
TI  - Regulating 'unruly' bodies: work tasks, conflict and violence in Britain's night
      time economy.
AB  - Security work in urban licensed premises is a risky occupation in Britain's fast
      expanding liminal night-time economy. Sociologically, little is known about this
      masculinist work, including those embodied strategies used by doorstaff or
      'bouncers' to regulate 'unruly' bodies in and around commercial space. Using
      participant observational data generated in south-west Britain, this paper
      describes how the door supervisors' routine work tasks (largely comprising
      requests and demands) provide the conditions of possibility for hierarchical
      conflict and (near) violence between themselves and (potential) customers inside
      and at the entrances to licensed premises. Besides providing a thick description
      of this work and the phenomenology of physical violence, the paper supports
      recent theoretical arguments for an explicitly embodied sociology. Centrally, the
      paper maintains that bodies matter and that an empirical, interpretative
      sociology cannot ignore the corporeal dimensions of social life if it is to
      arrive at an adequate understanding of everynight tensions and conflict.

PMID- 12227843
TI  - The theorization of social co-ordinations in differentiated societies: the theory
      of generalized symbolic media in Parsons, Luhmann and Habermas.
AB  - The problem of the differentiation of societies is at the core of the
      sociological imagination about the rise of modernity. In postwar sociology, T.
      Parsons developed the theory of generalized symbolic media in the mid-1960s to
      tackle, theoretically and historically, the issue of differentiation. According
      to him, the interchange media are defined as resources oriented to exchange
      processes between the subsystems of the social system. Starting with money,
      Parsons argues that the remaining media (power, influence, and value-commitments)
      have a set of characteristics defined as common properties for all media. After
      this first formulation, contemporary theorists such as Niklas Luhmann and Jurgen
      Habermas have developed and modified the Parsonian theory: Luhmann rejects the
      idea of interchange and proposes the use of communication; Habermas distinguishes
      between steering and communication media. In all three cases, the focus of the
      theory is on the characterization of the strongest dynamics of social co
      ordination present in differentiated societies. A major result of these
      developments is the inclusion of new dimensions on which to conceive the
      properties of media, not only those of money but also language. Beyond
      differences, then, it is proposed that there is only one theory of generalized
      symbolic media which can be understood as a progressive research programme, in
      Lakatos' terms. Finally, the hand-in-hand evolution between the theory of media
      and Habermas' and Luhmann's re-conceptualizations on societal differentiation in
      contemporary societies will also be revealed.

PMID- 12227844
TI  - Researching youth culture and popular music: a methodological critique.
AB  - In this article I argue the need for critical evaluation of qualitative research
      methodology in sociological studies of the relationship between youth culture and
      popular music. As the article illustrates, there is currently an absence of
      critical debate concerning methodological issues in this field of sociological
      research. In the first part of the article I begin to account for this absence by
      illustrating how early research on youth and music rejected the need for
      empirical research, relying instead on theories and concepts drawn from cultural
      Marxism. The second part of the article illustrates how the legacy of this early
      body of work in youth and music research manifests itself in current research
      which, although empirically grounded, is characterized by an almost total lack of
      engagement with methodological issues such as negotiating access to the field,
      management of field relations and ethical codes. Similarly problematic is the
      uncritical acceptance on the part of some researchers of their insider knowledge
      of particular youth musics and scenes as a means of gathering empirical data. In
      the final part of the article I focus on the issue of insider knowledge and the
      need for critical evaluation of its use as a methodological tool in field-based
      youth and music research.

PMID- 12227845
TI  - Hope and despair: making sense of politics in the twenty-first century.
AB  - As his life degenerates into accelerating cycles of chaos in the film
      'Clockwork', the headmaster, played by John Cleese, expresses his existential
      response to the latest crisis in his life: 'It's not the despair, I can cope with
      the despair. It's the hope I can't stand.' Politics as hope has fallen out of
      favour. Whether from cynicism, pessimism or realism--or a combination of all
      three--the standing of politics, let alone politicians, is at a very low ebb.
      This reality provides the opportunity to assess both causes and consequences by
      asking: how do we make sense of politics? The following discussion considers this
      vital question under four headings: context, participation, issues and goals.

PMID- 12227846
TI  - Power and agency.

PMID- 12227847
TI  - Clinical governance: implications for point-of-care testing.
AB  - With the introduction of clinical governance in the UK during 1997 and the shift
      in focus from a purely financial perspective to one of quality, it has become
      even more important that laboratories become involved with in vitro diagnostic
      devices (IVDs) used outside the laboratories by non-laboratory personnel, namely,
      point-of-care testing (POCT). The demand for POCT is increasing and its growth
      will continue with advances in technology, increasing pressure to shorten patient
      length of stay and requirements to decrease turnaround times, alongside the
      national initiatives to consolidate laboratories. However, clinical governance is
      about practising evidence-based medicine, and both the clinical and cost
      effectiveness of POCT continue to be debated. Accountability and leadership are
      pivotal in the implementation of clinical governance. Thus, the onus is on
      laboratories to take the lead for POCT and ensure that there is a robust risk
      management strategy to protect not only the staff, but, importantly, the patient.
      A rigorous POCT policy and national guidance must be adhered to. For a high
      quality POCT service to be delivered, fulfilling the requirements of clinical
      governance, a multidisciplinary local group must be established with recognized
      accountability, appropriate resources and, importantly, management support.

PMID- 12227848
TI  - Cyclosporin: revisions in monitoring guidelines and review of current analytical
      methods.
AB  - This article summarizes the main changes that have occurred in cyclosporin
      (ciclosporin) monitoring and measurement since the previous review in this
      journal. Cyclosporin has been reformulated to reduce variability in its
      absorption, leading to fewer post-transplant rejection episodes. Monitoring has
      mostly utilized the measurement of pre-dose blood levels of the drug, but more
      recently the potential benefit of using samples collected during the first few
      hours post-dose has been evaluated. Calculating the area under the cyclosporin
      concentration-time curve may be the ideal, but is not viable in the routine
      clinical situation and 2-h post-dose sampling seems likely to offer a practical
      clinical solution. Analytical methods based on high-performance liquid
      chromatography (HPLC) and immunoassay are available for the determination of
      whole blood cyclosporin concentrations. HPLC is specific but rarely used for
      routine monitoring, although HPLC-tandem mass spectrometry is making the
      technique more viable. New immunoassays have been introduced, but none are
      completely specific for the parent drug and all exhibit cross-reactivity towards
      cyclosporin metabolites. Immunoassays were originally designed for the lower
      cyclosporin concentrations seen in pre-dose samples, but are being evaluated and
      modified for determination of the higher concentrations seen 2 h post-dose.

PMID- 12227849
TI  - Analysis of serum angiotensin-converting enzyme.
AB  - Serum angiotensin-converting enzyme (SACE) levels are influenced by genetic
      polymorphism. Interpretation of serum levels with the appropriate genotypic
      reference range improves the diagnostic sensitivity of the assay for sarcoidosis.
      SACE assays are performed by a large number of routine clinical laboratories.
      However, there is no external quality assessment (EQA) for SACE other than an
      informal regional scheme. This showed analytical performance of SACE assays to be
      poor, with a diversity of reference ranges, leading to widely disparate clinical
      classification of EQA samples. Genetic polymorphism combined with poor analytical
      performance suggest that perhaps SACE assays should revert to being the province
      of specialized laboratories.

PMID- 12227850
TI  - Pregnancy and inherited metabolic disorders: maternal and fetal complications.
AB  - Some inherited metabolic disorders (IMDs) can cause significant complications
      during pregnancy, affecting the mother and/or the fetus. Although it appears that
      only a minority of IMDs have these effects, experience is still being acquired.
      For some disorders, patients will not have reached child-bearing age. Pregnancies
      in this group of patients will increase as the management of IMDs in childhood
      and adolescence improves. Clinicians should be aware of potential complications
      and consider carefully how best to manage these conditions. Ideally, patients
      should be followed up in adult life by a specialized clinical team, which can
      implement a planned approach to conception and pregnancy, but often this is not
      possible. For disorders where the risk of complications is well established (e.g.
      phenyl-ketonuria), optimal treatment may lead to a good fetal and maternal
      outcome. It is important also to consider the possibility of an IMD being present
      in fetuses of pregnancies that are affected by non-immune hydrops, maternal HELLP
      syndrome (haemolysis, elevated liver enzymes and low platelets) or acute fatty
      liver of pregnancy.

PMID- 12227851
TI  - Mitochondrial dysfunction and the role of the non-specialist laboratory.
AB  - Each human cell contains at least 1,000 mitochondria, each containing several
      copies of mitochondrial DNA. This DNA is tiny compared with the nuclear genome,
      and its structure and products have been fully elucidated. Whilst oxidative
      phosphorylation depends on the polypeptides encoded by mitochondrial DNA, it also
      requires a huge number of nuclear DNA products. Inherited deleterious mutations
      of mitochondrial DNA leading to inefficient oxidative phosphorylation have been
      described as 'mitochondrial disorders', with a variety of clinical presentations.
      When similar clinical presentations occur with no discernible mutation of
      mitochondrial DNA, histological and biochemical evidence is required for
      diagnosis. The number of these laboratory-proven inherited mitochondrial
      disorders is growing. It is also becoming clear that mitochondrial DNA defects
      can be acquired, the most common cause being therapy with highly active
      antiretroviral therapy (HAART) for human immunodeficiency virus-1 (HIV-1)
      infection. Whilst definitive diagnosis of inherited or acquired mitochrondrial
      dysfunction requires access to specialist laboratory techniques, routine
      laboratories have a role to play in the initial investigation and monitoring of
      these conditions.

PMID- 12227852
TI  - Solid-phase extraction in clinical biochemistry.
AB  - In order to measure low concentrations of analytes in plasma and urine, it is
      often necessary to extract and concentrate them. With solid-phase extraction
      (SPE), this is achieved by partitioning the analytes between a solid and a liquid
      or headspace vapour. A wide range of high-quality materials is now available to
      do this, offering a variety of separation modes for different applications. These
      include partitioning using reversed-phase, normal-phase, ion-exchange, restricted
      access and immunoaffinity sorbents or molecularly imprinted polymers and,
      increasingly, combinations of these processes. Solid-phase microextraction was
      introduced to analyse volatile and semi-volatile compounds. The range of sampling
      formats has expanded from simple packed syringes to cartridges, disks, SPE
      pipette tips and 96-well plates. These developments have facilitated automated
      off- and on-line sample processing. The basic principles of SPE and the recent
      innovations are reviewed here. This is a technological growth area. Some of the
      developments are finding application in clinical toxicology. However, they could
      also be of wider value in clinical chemistry--for example, for analyses of
      volatile and non-volatile metabolites, peptides, radioactive elements and trace
      metal speciation.

PMID- 12227853
TI  - Association between HaeIII polymorphism of scavenger receptor class B type I gene
      and plasma HDL-cholesterol concentration.
AB  - BACKGROUND: Evidence has recently been found for significant associations between
      genetic variation within the scavenger receptor class B type I gene (SR-BI),
      plasma lipids and anthropometric measurements in healthy Caucasians. The present
      case-control study was conducted to determine whether there is an association
      between three polymorphisms identified by the restriction endonucleases HaeIII,
      AluI and ApaI of SR-BI and coronary artery disease (CAD) in Korean subjects.
      METHODS: DNA was extracted from 137 subjects with CAD and 124 age-matched
      controls; it was amplified using the polymerase chain reaction. Individual
      alleles at each of the three polymorphic sites were identified by digestion with
      the appropriate restriction enzyme. RESULTS: Only a single allele was identified
      at the AluI and ApaI polymorphic sites. The frequency of the common (+) allele at
      the HaeIII polymorphic site was higher in CAD patients than in the controls (P =
      0.001). The concentrations of plasma HDL-cholesterol and apolipoprotein AI also
      varied significantly among HaeIII genotypes in the CAD patients. The common (+)
      allele of the HaeIII polymorphism was associated with a lower body mass index in
      female controls. CONCLUSIONS: Allele frequencies of the AluI and ApaI
      polymorphisms in this study were different to those in a Caucasian population
      studied previously, suggesting a difference in the genetic background. Further
      comparative studies of SR-BI polymorphism in other racial or ethnic groups should
      therefore prove to be of value.

PMID- 12227854
TI  - Immune complex transfer enzyme immunoassay for anti-ovalbumin IgA in serum.
AB  - BACKGROUND: An immune complex transfer enzyme immunoassay for antiovalbumin
      immunoglobulin A (IgA) was developed. METHODS: Serum-specific antibody was
      reacted simultaneously with 2,4-dinitrophenyl-bovine serum albumin-ovalbumin
      conjugate and ovalbumin-beta-D-galactosidase conjugate. The complex formed from
      the three components was trapped onto polystyrene balls coated with anti-2,4
      dinitrophenyl group immunoglobulin G, eluted with epsilonN-2,4-dinitrophenyl-L
      lysine and transferred to polystyrene balls coated with anti-human IgA alpha
      chain. Bound beta-D-galactosidase activity was determined by fluorometry. RESULTS
      & CONCLUSIONS: The detection limit of this method for the measurement of specific
      anti-ovalbumin IgA was 9 fmol/tube, which was 20-fold lower than that of the
      enzyme-linked immunosorbent assay (ELISA). Because serum interference with this
      method was lower than that with the ELISA, the detection limit of this method was
      300-fold lower than that by the ELISA. Anti-ovalbumin IgA was detected in 100% of
      healthy subjects, which was confirmed by pre-incubation with an excess amount of
      ovalbumin.

PMID- 12227855
TI  - Evaluation of a rapid micro-scale assay for tacrolimus by liquid chromatography
      tandem mass spectrometry.
AB  - BACKGROUND: The immunosuppressive drug tacrolimus has complex and unpredictable
      pharmacokinetics, therefore regular monitoring is required in patients receiving
      tacrolimus therapy. We have developed a liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method for measuring tacrolimus concentrations in whole
      blood and have compared it with a microparticle enzyme immunoassay. METHODS: For
      the LC-MS/MS assay, samples were prepared in a 96-deep well microtitre plate by
      adding 10 micro L of blood to 40 micro L of 0.1 mol/L zinc sulphate solution.
      Proteins were precipitated by adding 100 micro L acetonitrile containing
      ascomycin internal standard. After vigorous mixing and centrifugation, 20 micro L
      of the supernatant was injected into the LC-MS/MS system. A C18 cartridge (3 mm x
      4 mm) was eluted with a step gradient of 50% to 100% methanol containing 2 mmol/L
      ammonium acetate and 0.1% (v/v) formic acid, at 0.6 mL/min. The column was
      maintained at 55 degrees C. RESULTS: The retention times were 0.98 min for
      ascomycin and 0.98 min for tacrolimus. Cycle time was 2.5 min, injection to
      injection. The analytes were monitored using a Quattro micro trade mark tandem
      mass spectrometer operated in multiple reaction monitoring mode using the
      following transitions: m/z821 > 768 (tacrolimus) and m/z809 > 756 (ascomycin).
      The limit of quantitation was 0.5 micro g/L and the assay was linear up to 30
      micro g/L. Precision of the method, over the concentration range 2.5-15.0 micro
      g/L, was < 7% within-batch and < 6% between-batch. Total time to analyse 24
      samples including result generation was 90 min. CONCLUSION: We conclude that the
      LC-MS/MS method is quick, precise and robust and will provide a fast turn around
      of results for the transplant physician.

PMID- 12227856
TI  - Biochemical measures in a population-based study: effect of fasting duration and
      time of day.
AB  - BACKGROUND: Epidemiological studies generally aim to make simple but unbiased
      measurements of individuals. For this reason measurements of metabolic variables
      (including blood lipids, glucose and insulin) are usually carried out after a
      period of fasting. Few studies have examined the extent to which the use of a
      defined protocol for fasting in epidemiological studies abolishes the influence
      of fasting duration and time of day on biochemical measurements. METHODS: Cross
      sectional survey of British Regional Heart Study participants (4,252 men aged 60
      79 years), in which men without diabetes were asked to provide a blood sample
      after fasting for at least 6 h. Serum total, HDL and LDL cholesterol,
      triglyceride and insulin, and plasma glucose concentrations were measured between
      08:00 h and 18:00 h. RESULTS: Non-fasting men had lower mean LDL cholesterol and
      higher glucose, insulin and triglyceride levels than fasting men; these
      differences were more marked among diabetics. Among fasting men without diabetes,
      insulin and glucose levels were strongly related to time of day, falling
      gradually throughout the morning and remaining stable in the afternoon. Because
      of these relationships and the dependence of fasting duration on time of day,
      insulin and glucose displayed a periodic relation with fasting duration above 6
      h. These associations were largely abolished by adjustment for time of day;
      associations with time of day were unaffected by adjustment for fasting duration.
      Triglyceride concentrations fell with increasing fasting duration. This
      relationship was also mediated through a gradual increase in triglyceride levels
      throughout the day. Adjustments to compensate for these variations are described.
      DISCUSSION: Even after fasting, biochemical measurements may still differ in
      relation to fasting duration and time of day. In epidemiological studies, it is
      important to standardize both the period of fasting and the time of day as much
      as possible, and make adjustments where necessary.

PMID- 12227857
TI  - Near-patient testing of blood glucose using the Bayer Rapidlab 860 analyser in a
      regional neonatal unit.
AB  - BACKGROUND: We evaluated the use of the glucose biosensor on the Bayer Rapidlab
      860 (BR 860) blood gas analyser for neonates and compared it with two laboratory
      based methods for measuring blood glucose using the Yellow Springs Instruments
      2300 STAT PLUS (YSI) analyser and the Vitros 750 XRC (Vitros) analyser. METHODS:
      Arterial, capillary and venous blood samples were taken from 50 neonates, and
      blood glucose was measured using all three instruments. Blood pH, PO(2),
      haematocrit and plasma albumin data were also recorded. The effect of varying the
      degree of haemolysis and the haematocrit was examined using cord blood samples
      prepared in vitro. RESULTS: Day-to-day imprecision of the BR 860 was 4.90% at a
      mean glucose concentration of 2.55 mmol/L (n = 60), compared with 3.03% at 2.33
      mmol/L (n = 34) for the YSI and 2.64% at 3.52 mmol/L for the Vitros (n = 59).
      Using Deming regression, the BR 860 results correlated well with results produced
      on both the YSI (r = 0.962, n = 47, P < 0.001) and Vitros (r = 0.980, n = 46, P <
      0.001) analysers. Bland-Altman difference plots showed that the BR 860 had a mean
      of the differences of 0.30 mmol/L compared with the YSI and 0.09 mmol/L compared
      with the Vitros. The Bland-Altman standard deviation of the differences was 0.46
      mmol/L when the BR 860 was compared with the YSI and 0.31 mmol/L when the BR 860
      was compared with the Vitros. No significant correlation was found between the BR
      860 glucose measurements and haematocrit, degree of sample haemolysis, plasma
      albumin, blood pH or PO(2). CONCLUSIONS: The BR 860 analyser provides neonatal
      blood glucose measurements in the clinical setting of a neonatal unit that
      compare well with results obtained using laboratory-based methods.

PMID- 12227858
TI  - Point-of-care testing of blood glucose in the neonatal unit using the AVL Omni 9
      analyser.
AB  - BACKGROUND: Blood glucose measurements in newborns at risk of hypoglycaemia are
      an essential part of their medical management. Blood glucose measurements
      obtained by point-of-care testing using an AVL Omni 9 blood gas and metabolite
      analyser were compared with those obtained in the central laboratory using a Dade
      Dimension RXL analyser. METHODS: Blood glucose was measured at the point of care
      by nursing staff using an AVL Omni 9 blood gas and metabolite analyser and
      compared to results obtained in the central laboratory using a DADE Dimension RXL
      analyser. In total, 123 samples were taken from 114 babies admitted to the
      neonatal unit. RESULTS: The limits of agreement between the AVL Omni 9 and the
      central laboratory were 0.0 +/- 0.6 mmol/L for glucose values between 0.5 and 13
      mmol/L. Regression analysis showed: AVL Omni 9 glucose = 0.977 x plasma
      glucose+0.14. There was also a good correlation (r = 0.92) between the AVL Omni 9
      and the DADE Dimension RXL analyser for glucose values < 3 mmol/L. The limits of
      agreement for the AVL Omni 9 when compared with the DADE Dimension RXL analyser
      were -0.1 +/- 0.5 mmol/L. DISCUSSION: Point-of-care testing of blood glucose
      using the AVL Omni 9 blood gas and metabolite analyser is a reliable means of
      measuring blood glucose and has the advantage of providing a fast result using
      small volumes of blood.

PMID- 12227859
TI  - Rapid measurement of insulin using the Abbott IMx: application to the management
      of insulinoma.
AB  - BACKGROUND: Patients with multiple endocrine neoplasia (type 1) often present
      with multiple pancreatic endocrine tumours, such as insulinomas. A major
      difficulty in the surgical treatment of such patients is identifying which
      tumours are functionally active and therefore need to be resected for a cure. The
      objective of this study was to develop a rapid insulin assay that could be used
      intraoperatively for identifying insulinomas from pancreatic aspirates. METHODS:
      By reducing the incubation time and by increasing the sample volume, a rapid
      insulin assay was developed on the IMx analyser. This was used to measure insulin
      from tissue aspirates collected from suspected insulinomas under ultrasound
      guidance. RESULTS: The rapid insulin assay (y) could be performed in 14 min and
      showed a good correlation with the standard IMx (x) insulin assay (y = 0.808x +
      0.04; r(2) = 0.986). Using the rapid insulin assay on pancreatic tissue
      aspirates, insulinomas could be readily distinguished from normal pancreatic
      tissue or from non-functional adenomas based on a marked increase in insulin
      content. CONCLUSION: In summary, a new rapid assay for insulin is described that
      compares favourably to the standard IMx insulin assay and can potentially be used
      intraoperatively on pancreatic aspirates for identifying functionally active
      insulinomas.

PMID- 12227860
TI  - Continuous glucose monitoring and haemoglobin A(1c).
AB  - BACKGROUND: Measurement of HbA(1c) is the standard test for assessment of
      glycaemic control in diabetic subjects. Using new glucose sensing technology we
      re-evaluated the significance of HbA(1c) in terms of the aspects of the blood
      profile it measures in patients with diabetes. METHODS: In a group of 27 patients
      with type 1 diabetes, interstitial fluid glucose concentrations were monitored
      for a mean of 2.6 days using the Continuous Glucose Monitoring System trade mark
      (MiniMed Inc, CA, USA). Results were correlated with an HBA(1c) measurement taken
      at the time of sensor insertion. RESULTS: Results were available in 25 subjects,
      two datasets being lost due to patient error. There was a correlation between
      mean sensor glucose value, and the HbA(1c) value (r = 0.59, P = 0.002). The
      correlation with standard deviation of the readings was weaker (r = 0.3, P =
      0.15). No other descriptor of the sensor glucose concentration correlated with
      HbA(1c). CONCLUSION: The mean interstitial glucose concentration recorded with
      the Continuous Glucose Monitoring System correlates with HbA(1c) level recorded
      at the time, but with no other marker of glucose control in diabetic subjects.
      These results have implications for the interpretation of HbA(1c) concentrations
      in type 1 diabetes.

PMID- 12227861
TI  - Stability of ascorbic acid in serum and plasma prior to analysis.
AB  - INTRODUCTION: The stability of ascorbic acid in serum and plasma prior to
      analysis was studied. METHODS: Blood samples were collected from ten healthy
      subjects into Vacutainer tubes containing either dipotassium EDTA, lithium
      heparin or no additive. Ascorbic acid was analysed following immediate separation
      and preservation of samples, following delayed separation for 2 h and after
      delayed deproteinization and preservation for 2, 5 and 8 h. Deproteinization and
      preservation were achieved using a solution containing perchloric acid, EDTA and
      dithiothreitol. Ascorbic acid was analysed by high-performance liquid
      chromatography. RESULTS: Blood collected into EDTA and separated, deproteinized
      and preserved immediately gave the highest yield of ascorbic acid. Loss of
      analyte after delayed separation was least for EDTA tubes (median 7%, range 4
      13%), followed by lithium-heparin (median 18%, range 10-32%) and serum (median
      26%, range 14-50%). Immediate separation of samples but delayed deproteinization
      and preservation also resulted in substantial losses of ascorbic acid.
      CONCLUSION: Minimum loss of ascorbic acid is achieved if blood is collected into
      tubes containing dipotassium EDTA and separated within 2 h, followed by immediate
      deproteinization and preservation.

PMID- 12227862
TI  - Discrepancy between visual and spectrophotometric assessment of sample
      haemolysis.
AB  - BACKGROUND: This study assessed the agreement between visual grading of sample
      haemolysis with automated haemolysis index (H index) measurement on the Roche 917
      clinical chemistry analyser. METHODS: The H indices of 800 serum potassium
      samples and 800 EDTA plasma troponin I samples were compared with routine visual
      grading of sample haemolysis by technologists. Photographs of mild (haemoglobin 1
      g/L), moderate (2.5 g/L) and severe (5 g/L) haemolysis were available for
      reference. RESULTS: For serum samples, the weighted kappa coefficient was 0.42
      with an 8.0% haemolysis rate determined by visual inspection and 3.4% by H index.
      For EDTA-plasma samples, the weighted kappa coefficient was 0.35 with a 4.5%
      haemolysis rate determined by visual inspection and 7.9% by H index. CONCLUSION:
      Visual assessment of sample haemolysis is unreliable and can give variable
      results depending on sample type. Laboratories should consider investigating
      sample haemolysis using automated haemolysis index measurement as an alternative
      to visual grading whenever it is available.

PMID- 12227863
TI  - Macro-alkaline phosphatase due to IgG kappa complex: demonstration with
      polyethylene glycol precipitation and immunofixation.
AB  - An otherwise unexplained, persistently elevated plasma alkaline phosphatase
      concentration in a 71-year-old woman was found to be attributable to the presence
      of macro-alkaline phosphatase using polyethylene glycol precipitation. Gel
      filtration showed two high MW peaks with masses of about 330 kDa and 560 kDa. The
      alkaline phosphatase (ALP) complex was characterized by immunoelectrophoresis as
      a complex with IgG with kappa light chains.

PMID- 12227864
TI  - Japanese familial hypercholesterolaemia with a 327insC mutation in the LDL
      receptor gene.
AB  - Mutations in the LDL receptor (LDLR) cause familial hypercholesterolaemia (FH) in
      an autosomal dominant manner. The condition frequently progresses to coronary
      atherosclerosis. We describe a patient with FH, but without ischaemic heart
      disease, who had a novel frameshift mutation (327insC) in exon 4 of the LDLR
      gene. This mutation introduced a premature termination codon (TGA, codon 158).
      The patient was a 59-year-old man who had presented with hypercholesterolaemia
      and a plasma total cholesterol (TC) concentration of 12.2 mmol/L at age 44 years.
      The mutation 327insC in this patient was heterozygous and hypercholesterolaemia
      was common within his family. Despite taking lipid-lowering medications (probucol
      and pravastatin) for more than 20 years, his TC concentration hardly fell below
      7.8 mmol/L. However, neither the patient nor anyone else in his family developed
      characteristic symptoms of ischaemic heart disease or xanthoma. This patient was
      discovered by an intensive mutation survey among 22 unrelated Japanese with FH
      mainly in the Kanto area of Japan, suggesting a low incidence of the mutation in
      the area.

PMID- 12227865
TI  - Gamma heavy chain disease screening showing a discrepancy between electrophoretic
      and nephelometric determinations of serum gamma globulin concentration.
AB  - A 75-year-old woman with rheumatoid arthritis showed a discrepancy between the
      reduced level of serum gamma globulin on cellulose acetate electrophoresis and
      the normal level of serum IgG determined by laser nephelometry. Although no M
      peak was detectable on cellulose acetate electrophoresis, immunoelectrophoresis
      of the patient's serum revealed a monoclonal protein reacting with anti-IgG
      antiserum but not with anti-kappa or anti-lambda light chain antiserum. Western
      blotting of the patient's serum showed abnormal low-molecular-weight gamma
      chains. Thus, the patient was diagnosed with gamma heavy chain disease. A
      comparison of gamma globulin levels determined by different methods may be useful
      when screening for this disease.

PMID- 12227866
TI  - Standardization of glycated haemoglobin.

PMID- 12227871
TI  - Advised best practice for the use of emollients in eczema and other dry skin
      conditions.
AB  - The recent Dermatological Care Working Group report highlighted important
      deficiencies in the dermatology service in the UK and recommended that care
      should move closer to the patient. The report stated that 'expert patients' could
      become 'sharers in their care' and are best placed to improve their own self
      management. One area that could benefit greatly from increased patient education
      and participation is the use of emollients. Emollients are frequently prescribed
      for patients with eczema and other dry skin conditions. Although the benefits of
      emollient therapy are widely accepted, prescribing practices vary considerably,
      often according to physicians' individual preferences. Patients can receive
      confusing or conflicting treatment advice, leading to frustration, non
      compliance, and difficulty in following an effective regimen. To promote the
      effective use of emollients it is important for patients and health professionals
      to understand the functions of the skin and the principles of emollient use and
      application. We propose a set of simple guidelines for emollient therapy in
      eczema care to improve day-to-day management by health professionals in the
      community and to promote consistent practices by patients. These guidelines form
      the ABC dry skin and eczema management programme supported by the National Eczema
      Society and accredited by the British Skin Foundation.

PMID- 12227872
TI  - Comparative efficacy of clindamycin and benzoyl peroxide for in vivo suppression
      of Propionibacterium acnes.
AB  - BACKGROUND: Benzoyl peroxide and clindamycin are the two most widely prescribed
      topical antimicrobials in the treatment of acne. AIM: To compare the
      antimicrobial efficacy, in vivo, of benzoyl peroxide and clindamycin against
      Propionibacterium acnes. METHODS: Two groups of 10 subjects each, with comparable
      mean P. acnes baseline counts of log 5.75 to 5.85, underwent twice daily
      application of benzoyl peroxide or clindamycin for 14 days. RESULTS: The results
      of quantitatively sampling P. acnes after 3, 7 and 14 days of treatment showed
      that Triaz 6% benzoyl peroxide special gel produced faster and significantly
      greater reductions in P. acnes than did the 1% clindamycin phosphate in Cleocin-T
      lotion (p < 0.01). These results were paralleled by the greater reductions
      produced by Triaz versus Cleocin (p < 0.05) in P. acnes fluorescence. CONCLUSION:
      Benzoyl peroxide formulations suppress the follicular population of P. acnes more
      rapidly and to a greater degree than topical antibiotics such as clindamycin.

PMID- 12227873
TI  - Clinical evaluation of Double Strength Isotrexin versus Benzamycin in the topical
      treatment of mild to moderate acne vulgaris.
AB  - BACKGROUND: Topical retinoid therapy has been shown to be an effective means of
      treating both the inflammatory and non-inflammatory lesions of acne vulgaris.
      AIM: To assess the efficacy and safety of the test product, a gel containing
      isotretinoin 0.1% w/w and erythromycin 4.0% w/w, with a currently used and
      effective treatment for mild to moderate acne vulgaris, a gel containing benzoyl
      peroxide 5.0% w/w and erythromycin 3.0% w/w. METHODS: This multi-centre, single
      blind (investigator blind), parallel group study compared the efficacy and safety
      of isotretinoin/erythromycin gel (Double Strength Isotrexin) once daily against
      benzoyl peroxide/erythromycin gel (Benzamycin twice daily in the topical
      treatment of mild to moderate acne vulgaris. Patients (n = 188) with a history
      (mean duration 3.3 years) of facial acne vulgaris and with 15-100 inflammatory
      lesions and/or 15-100 non-inflammatory lesions, but not more than three
      nodulocystic lesions, were included. At baseline and weeks 2, 4, 8 and 12, the
      investigator assessed efficacy (total number and severity of inflammatory and non
      inflammatory lesions and acne grade) while subjective global change assessments
      of facial acne from baseline and symptom-specific skin tolerance were assessed by
      the patient. The investigator recorded an overall global assessment of skin
      tolerability at week 12. Adverse events were recorded throughout. RESULTS: The
      treatments were comparable with regard to their effects on inflammatory and non
      inflammatory lesions and acne grade. Few adverse events were considered to be
      treatment-related. Both the isotretinoin/erythromycin and benzoyl
      peroxide/erythromycin gels were generally well tolerated. Compliance was better
      with the isotretinoin/erythromycin gel, which had the advantages of not requiring
      mixing or storage in a refrigerator, and was applied once rather than twice
      daily. CONCLUSIONS: Isotretinoin/erythromycin gel given only once daily showed
      comparable efficacy with benzoyl peroxide/erythromycin given twice daily in the
      treatment of mild to moderate acne vulgaris of the face.

PMID- 12227874
TI  - Fabric-staining properties and washability of a novel liposomal dithranol
      formulation.
AB  - AIM: To test the staining potential of a novel liposomal dithranol gel on
      different types of fabrics and compare it with the only commercially available
      dithranol preparation in India, Derobin. METHODS: Pure cotton, pure polyester and
      four blends of the two fabrics were tested for staining and washability. RESULTS:
      Both products showed the least staining and spreading on pure cotton with
      progressively worse stains as the proportion of polyester in the fabric
      increased. When compared with each other the liposomal dithranol gel showed
      markedly lighter staining than Derobin on all fabrics. It also washed off
      completely with water whereas the Derobin stains could not be washed off, even
      with detergent. CONCLUSION: The liposomal gel due to its superior staining
      properties may potentially increase the acceptability of dithranol amongst
      psoriasis patients.

PMID- 12227875
TI  - Topical imiquimod treatment of superficial and nodular basal cell carcinomas in
      patients affected by basal cell nevus syndrome: a preliminary report.
AB  - BACKGROUND: Imiquimod 5% cream has been shown to be effective in the treatment of
      superficial basal cell carcinomas (sBCCs). OBJECTIVE: To evaluate the efficacy,
      safety and compliance of imiquimod 5% cream for the treatment of sBCCs and
      nodular BCCs (nBCCs) in patients affected by basal cell nevus syndrome.
      PATIENTS/METHODS: Three patients (two male, one female) were enrolled in the
      study. Nine tumors (five sBCCs and four nBCCs), all ranging in size from 0.5 cm
      to 1 cm, were treated. Treatment consisted for sBCCs of three weekly applications
      and for nBCCs of five weekly applications for 8 weeks. Histological examination
      was performed at the beginning and at the end of the study. For small tumors,
      similar-appearing lesions were removed for baseline histological confirmation.
      Follow-up was performed at 1-week intervals in order to carefully detect any
      change. RESULTS: Three sBCCs cleared clinically after 4 weeks of treatment and
      two nBCCs after 8 weeks. The remaining four lesions showed excellent clinical
      responses with evident (>50%) size reduction at 6 weeks, but no further
      improvement. Histological examination with multiple-step sections confirmed
      complete clearing for those lesions showing clinical resolution, except for one
      nBCC that showed scant tumor remnants. Local adverse effects (itching, erythema
      and bleeding) were mild and did not prompt discontinuation of treatment. No
      systemic side effects were noted. CONCLUSIONS: Imiquimod 5% cream is an effective
      therapeutic option for both sBCC and nBCC in patients with basal cell nevus
      syndrome. The treatment was very well received by all patients engaged in the
      study, who stated their appreciation for a topical treatment rather than multiple
      surgical excisions. A higher number of applications and longer treatment periods
      are required for nBCCs.

PMID- 12227876
TI  - Limited benefit of topical calcipotriol in lichen planus treatment: a preliminary
      study.
AB  - BACKGROUND: Lichen planus (LP) is a papulosquamous dermatosis in which
      immunologic mechanisms play an important role in its pathogenesis. Topical
      calcipotriol, which mainly stimulates differentiation and inhibits proliferation
      of keratinocytes, also has immunosuppressive and anti-inflammatory functions.
      AIM: To investigate the therapeutical effects of topical calcipotriol in LP.
      METHODS: A total of 18 histopathologically proved LP patients were advised to
      apply calcipotriol ointment twice daily to all affected skin areas except
      genitalia. Clinical evaluation of all patients was performed monthly and response
      to treatment was assessed on clinical grounds (erythematous and/or violaceous
      color, thickness and scale of the lesions) as partial, complete or no response.
      If there was no response at the end of the second month, topical calcipotriol was
      stopped. If there was partial clinical improvement at the end of the second
      month, the treatment was continued for one additional month. RESULTS: In all, 16
      patients completed the study. Of the study population, 56.25% (9/16) responded to
      topical calcipotriol treatment which was used for a maximum of 3 months. Complete
      clearing of the lesions with post-inflammatory hyperpigmentation and partial
      improvement were obtained in 31.25% (5/16) and 25% (4/16) of the patients,
      respectively. No improvement was observed in 43.75% (7/16) of the patients.
      CONCLUSION: Topical calcipotriol can be used in the treatment of LP as a
      therapeutic option, although it is not the first-choice drug.

PMID- 12227877
TI  - Free radical scavenging and skin penetration of troxerutin and vitamin
      derivatives.
AB  - BACKGROUND: By its 'protective function', human skin is a potential target for
      the production of free radicals. The role played by topically applied
      antioxidants as inhibitors of oxidative stress damage was felt to be worth
      investigation. OBJECTIVE: To investigate the free radical scavenging (superoxide,
      hydroxyl and peroxyl radicals) and skin penetration of troxerutin in association
      with ascorbyl palmitate and alpha-tocopheryl succinate, esters of two vitamins
      commonly used in skin care products. METHODS: The compounds' scavenging
      activities, in a concentration-dependent manner, were as follows: hydroxyl
      radicals in a Fenton-based assay; superoxide radicals in a hypoxanthine/xanthine
      oxidase system; and lipid peroxidation inhibition of liver microsomes was induced
      by 2,2'-azobis-(2-amidinopropane) dihydrochloride (ABAP). RESULTS: A synergic
      action was observed between alpha-tocopheryl succinate and troxerutin for
      hydroxyl radical scavenging, between the three compounds for superoxide
      scavenging and between troxerutin and ascorbyl palmitate in lipid peroxidation
      inhibition. CONCLUSION: Using a stripping method, it was shown that the three
      substances, incorporated in a pharmaceutical preparation, permeated through human
      epidermis. Thus, this association can improve skin care products for preventing
      free radical-mediated damage.

PMID- 12227878
TI  - Successful treatment with doxycycline and nicotinamide of two cases of persistent
      pemphigoid gestationis.
AB  - Pemphigoid gestationis (PG) is a rare dermal-epidermal autoimmune bullous disease
      of pregnancy and postpartum, which relapses more seriously and earlier during
      following pregnancies. PG also occurs in association with trophoblastic tumours
      or oral contraceptive treatment. The term 'persistent PG' represents the cases
      where active disease persists for months to many years after delivery. Four cases
      of persistent PG have been reported to date in the literature. So far, systemic
      cortico-steroids have been the main PG therapy and the use of cyclophosphamide,
      dapsone, pyridoxine, methotrexate, plasmapheresis or ritodrine has also been
      reported, with contradictory results. In this paper are described two patients
      with persistent PG who were successfully treated with doxycycline (200 mg/day)
      and nicotinamide (500 mg/day), a treatment that was demonstrated to be safe and
      efficacious in bullous pemphigoid.

PMID- 12227879
TI  - Multiple milia due to radiotherapy.
AB  - We report the appearance of multiple milia in a 61 year old woman appearing 7
      years after irradiation for breast cancer. The lesions were confined to the
      irradiated field.

PMID- 12227880
TI  - Isotretinoin in Denmark -- 20 years on.

PMID- 12227882
TI  - Immunological and dermatological impact of progesterone.
AB  - C21 steroids and especially progesterone are involved in various physiological
      processes besides reproduction. Langerhans cells are becoming a major topic in
      immunology and, from this point, it is of high interest that progesterone is able
      to increase the number of Langerhans cells in different epithelial cells. This
      has an impact for a gender specificity of HIV1 infection, and also for the high
      premenstrual incidence of sexually transmitted diseases. Matrix metalloproteinase
      activity is of high physiological importance for tissue regeneration;
      progesterone suppresses the expression of some members of the matrix
      metalloproteinase super-family and reduces the collagenolytic activity. These
      effects can be observed during pregnancy, but are not only apparent on the
      myometrium; the suppressing effect of progesterone on matrix metalloproteinases
      can also be observed in the skin. The dermatological aspect of this observation
      is discussed.

PMID- 12227881
TI  - How progestins influence the cardiovascular effect of hormone replacement
      therapy.
AB  - Hormone replacement therapy aims to protect against osteoporosis and alleviate
      fastidious menopausal symptoms such as hot flushes, depression, sleep
      disturbances and vaginal dryness. In view of the acknowledgement of estrogen
      deficiency as a major trigger for the acceleration of cardiovascular risk after
      menopause, hormone replacement therapy may also be proposed as a substantial
      beneficial cardioprotective agent. The effects of progestins on lipoprotein
      profile and vasomotor tone are dependent on the chemical structure and the scheme
      of administration of progestins, with androgenic progestins and cyclical therapy
      having a potential detrimental effect. Prospective primary and secondary
      prevention studies, however, suggest that the adjunct of non-androgenic
      progestins to estrogen therapy is at least as effective as estrogen replacement
      therapy in reducing cardiovascular mortality and morbidity. Data from recent
      randomized secondary prevention studies have to be viewed with caution.

PMID- 12227883
TI  - Current place of progestins in the treatment of endometriosis-related complaints.
AB  - Oral progestins have been used for the treatment of endometriosis and
      endometriosis-associated complaints for more than 40 years. The mechanism of
      action on the menstrual cycle is well understood; however, the mechanism of
      action on endometriosis is still a matter of debate. The different progestins are
      able to stop proliferation in endometriotic implants and to induce regressive
      change to certain degrees; they are not able to heal endometriosis because
      endometriosis is a chronic and recurrent disease. For this reason, no medical
      treatment can heal endometriosis and repeat medication is necessary in the
      medical management of this disease. Progestins--especially non-androgenic
      progestins--are well tolerated and have only few side-effects; they can be used
      repeatedly or continuously over a long period of time.

PMID- 12227884
TI  - Progestins and endometrial cancer.
AB  - Premenopausal women--especially young women--with endometrial cancer stage I may
      be treated successfully with progestins alone as primary therapy to preserve
      their child-bearing potential. There is some indication that progestins could be
      used in neoadjuvant fashion. Individualization of adjuvant treatment with
      radiation or progestins and in combination seems possible. Progestins have an
      established place in the palliative treatment of women with advanced cancer. In
      addition, progestins can be used in advanced and/or recurrent endometrial cancer
      in combination with chemotherapy and tamoxifen.

PMID- 12227885
TI  - Cyclic progestin therapy for the management of mastopathy and mastodynia.
AB  - The management of benign diseases of the breast aims to halt the progression of
      fibrocystic transformation and to eliminate the symptoms of pain and breast
      tenderness. Progestins can be used for this purpose. In a controlled, randomized,
      double-blind, parallel-group study we treated 31 women with mastopathy/mastodynia
      with the progestins medrogestone (10 mg/day) or dydrogesterone (10 mg/day) from
      day 14 to day 25 for six cycles. Before, during and at the end of therapy the
      following parameters were evaluated: subjective symptoms (pain, tenderness,
      impairment of daily activities), palpatory findings, sonographic diagnosis and
      sex hormone profiles. Cyclic administration of the low-dose progestins
      medrogestone and dydrogesterone proved to be an effective and safe treatment of
      mastodynia and mastopathy. The objective parameters palpatory findings and
      sonographic imaging of breast nodules and cysts improved in more than 50% of
      patients. Improvement was particularly marked in women with low progesterone
      levels in the second half of the cycle. After six treatment cycles, 75% of the
      patients treated with dydrogesterone and 86% of the patients treated with
      medrogestone were completely pain-free.

PMID- 12227886
TI  - Biological effects of progestins in breast cancer.
AB  - The action of progestins is derived from many factors: structure, affinity for
      the progesterone receptor or for other steroid receptors, the target tissue
      considered, the biological response, the experimental conditions, the dose and
      metabolic transformation. The proliferative response to progestins in human
      breast cancer cells is contradictory: some progestins inhibit, others stimulate,
      have no effect at all, or have a dual action. For instance, medroxyprogesterone
      acetate has a stimulatory effect on breast cancer cells after a short period of
      treatment, but this effect becomes inhibitory when treatment is prolonged. It has
      been demonstrated that, in hormone-dependent breast cancer cells, various
      progestins (nomegestrol acetate, medrogestone, promegestone) are potent sulfatase
      inhibitory agents. The progestins can also involve the inhibition of the mRNA
      expression of this enzyme. In another series of studies it was also demonstrated
      that some progestins are very active in inhibiting 17beta-hydroxysteroid
      dehydrogenase for the conversion of estrone to estradiol. More recently it was
      observed that the progestins promegestone and medrogestone stimulate
      sulfotransferase for the formation of estrogen sulfates. Consequently, the action
      of progestins in blocking estradiol formation via sulfatase, or in stimulating
      the effect on sulfotransferase activity, can open interesting and new
      possibilities in clinical applications in breast cancer.

PMID- 12227887
TI  - Breast cancer and hormone replacement therapy: putting the risk into perspective.
AB  - Data on hormone replacement therapy and breast cancer risk come from a number of
      observational studies (mostly American studies). Those published up to 1995 were
      reanalyzed by the Collaborative Group on Hormonal Factors in Breast Cancer
      (CGHFBC). They involved populations where exceedingly high estrogen doses were
      used as first-line therapy, and a progestin was added in a minority of women.
      Overall, the CGHFBC reanalysis found that the relative risk increased by 0.023
      for each year of use (with an absolute excess risk of two or six cases out of
      1000 women treated for 5 or 10 years, respectively). Further American studies,
      published in 2000 and involving populations where lower doses were used, showed a
      risk increase of 0.01 per year of estrogen-only use. Both the CGHFBC reanalysis
      and the further studies did not find an increase of risk in treated overweight
      women. Possibly, overweight women already have a maximal estrogenic stimulus on
      the breast due to extraglandular estrogen production. An additional explanation
      could be that oral estrogens, through their hepatocellular effects, reverse some
      biological features of obesity (e.g. decreased sex hormone binding globulin level
      and increased insulin-like growth factor-I bioactivity) that potentially increase
      breast cancer risk, so balancing the estrogen stimulation. The CGHFBC reanalysis
      did not show a substantial difference in breast cancer risk between the majority
      using estrogen alone and the small minority using estrogen plus progestin.
      Conversely, Swedish studies and the recent American studies suggest that the risk
      increase could be higher with the addition of a progestin, compared with estrogen
      only use. The biological effect of progesterone/progestins on the breast tissue
      is controversial. Even if the observed increase in risk could be partially
      ascribed to non-progesterone-like effects of some progestins (e.g. opposing the
      hepatocellular effects of oral estrogens) and also (in the American studies) to
      use-bias, a detrimental action due to progesterone-like effects cannot be
      excluded. However, the theoretical possibility exists that low doses of oral
      estrogens, plus a progestin providing progesterone-like effects only, will be
      shown to be associated with a limited breast cancer risk increase.

PMID- 12227888
TI  - Levels of estrogen and progesterone receptors in the myometrium and leiomyoma
      tissue after suppression of estrogens with gonadotropin releasing hormone
      analogs.
AB  - Gonadotropin releasing hormone (GnRH) agonists are successfully used in the
      treatment of uterine leiomyomas. Different GnRH agonists may have different local
      effects on steroid receptors. This study was designed to evaluate potential
      differences in this respect between triptorelin (Decapeptyl) and goserelin
      (Zoladex) in a randomized controlled multicenter study using untreated patients
      during the luteal phase of their menstrual cycle as controls. Estrogen receptors
      (ERs) and progestin receptors (PRs) were measured by ligand binding assay in
      myoma and myometrium tissue following a 4-month treatment course with one of the
      GnRH analogs. In 18 untreated patients median values of ER and PR contents were
      comparable in myoma and myometrium: for ER at median levels of 56 and 43 fmol/mg
      protein, respectively; and for PR, median binding capacities were 690 and 730
      fmol/mg protein, respectively. Both types of GnRH treatment (total number of
      patients 34) were associated with significant rises in ER in myoma (to a median
      level of 279 fmol/mg protein, p<0.001) and myometrium (to a median level of 109
      fmol/mg protein, p<0.01). The increase in ER in myomas was significantly
      (p<0.001) greater than in myometria of the same patients (n=30). After treatment,
      PR in myomas (median level 520 fmol/mg protein) did not change significantly, but
      a significant (p<0.05) decrease was found for myometria (median level of 320
      fmol/mg protein). Thus, ER and PR concentrations in myoma and myometrium are
      comparable before treatment, but estrogen suppression with GnRH analogs leads to
      a larger increase of ER level in leiomyomas than in myometrium, without an effect
      on PR, whereas myometria had lower PR levels. Therefore, leiomyoma reacts
      differently from myometrium towards lowered steroid concentrations in the
      circulation. Since the PR is considered to be a marker of estrogenic stimulation,
      this indicates remaining estrogenic effects on leiomyomas despite the large
      decrease of plasma estrogen concentrations.

PMID- 12227889
TI  - Review: female sex hormones, autoimmune diseases and immune response.

PMID- 12227896
TI  - Progestins and cancer.
AB  - The role of progestins in breast tissue is less well defined than in the
      endometrium. Although in vitro studies have shown that progestins induce a
      similar decrease in both estrogen and progesterone receptors and an increase in
      17beta-estradiol dehydrogenase in the breast as in the endometrium, epidemiologic
      studies have suggested that progestins prevent endometrial cancer, but do not
      reverse the estrogen-related increase in breast cancer risk in long-term hormone
      replacement therapy (HRT). Other studies have also suggested a protective effect
      for progestins on breast tissue. The dual effect of progesterone and progestins
      on the cell cycle has been demonstrated, suggesting that according to the
      duration of administration, the same steroid can induce cells to enter the
      multiplication phase or to enter a resting state. Progestins exert different
      effects according to the steroid from which they are derived, e.g. pregnanes
      derived from progesterone, estranes or gonanes derived from testosterone. Some
      estrane derivatives are able to stimulate breast cell multiplication in vitro
      through an estrogen receptor-mediated pathway. Most pregnanes do not exert such
      an effect. Also, some pregnane derivatives stimulate apoptosis, leading to cell
      death. However, it is well established that high doses of progestins have been
      successfully used in the treatment of advanced breast cancer as second-line
      endocrine therapy. Finally, striking differences have been observed in progestin
      use in Europe and in the USA. In France, where the rate of progestin use per head
      is higher than in the USA, the rate of breast cancer has not increased as sharply
      as observed in North America. Although cancer genesis is multifactorial, it may
      be concluded that progestins do protect endometrial tissue against the
      proliferative action of estrogen and if they do not protect breast tissue, at
      least they do not stimulate its proliferation. Also, they are useful agents as a
      second-line therapy for breast cancer, when used at high doses.

PMID- 12227897
TI  - Biological effects of progestins in breast cancer.
AB  - Developments in the synthesis of different progestins have opened up new
      possibilities for the biological effects and therapeutic uses of these compounds.
      The actions of progestins are a function of their structure, affinity to the
      progesterone receptor or to other steroid receptors, the target tissue
      considered, the biological response, the experimental conditions, dose, and
      metabolic transformation. Data on the action of progestins in breast cancer
      patients are very limited. A positive response with the progestins
      medroxyprogesterone acetate and megestrol acetate has been obtained in
      postmenopausal patients with advanced breast cancer. However, extensive
      information on the effect of progestins was obtained in in vitro studies using
      hormone-dependent and hormone-independent human mammary cancer cell lines. It was
      demonstrated that in hormone-dependent breast cancer cells, various progestins
      (nomegestrol acetate, medrogestone, promegestone) as well as tibolone, are potent
      sulfatase-inhibitory agents. Progestins may also be involved in the inhibition of
      the mRNA of this enzyme. In another series of studies, it was also demonstrated
      that various progestins are very active in inhibiting the 17 beta-hydroxysteroid
      dehydrogenase for the conversion of estrone to estradiol. More recently, it has
      been observed that promegestone or medrogestone stimulates the sulfotransferase
      for the formation of estrogen sulfates. Clinical trials of these enzymatic
      effects on the formation and transformation of estradiol in breast cancer
      patients could be the next step to investigate new therapeutic possibilities for
      this disease.

PMID- 12227898
TI  - Progestins and uterine leiomyoma.
AB  - Myomas are the most frequent benign gynecological tumors and are responsible for
      several symptoms and complaints. Their etiology is unknown and their pathology
      and proliferation is poorly understood. Besides the importance of estrogens for
      development and growth of the myoma, progesterone seems to play an important role
      in the modulation of mitotic activity, local growth factors and growth factor
      receptors, as well as other paracrine mechanisms.

PMID- 12227899
TI  - Effects of progestins on bone: an update.

PMID- 12227900
TI  - Progesterone and neurology.
AB  - Neurological diseases are frequently observed in perimenopausal women and can be
      characterized by their gender-specific occurrence. These observations raise the
      question whether sex steroids are also involved in neurological diseases.
      Epidemiological data have shown that in Austria in 1993, the prescription rate of
      psychotropics, hypnotics, and analeptics for women aged 50-55 years increased
      over 300% compared to other age groups. In males of the same age, an increase of
      the prescription rate was not observed. Molecular pharmacology research over the
      last ten years has shown that sex steroids may interact with the central nervous
      system via GABA receptors as well as with the peripheral nervous system. These
      observations confirm the epidemiological finding that neurological and
      psychological functions may also be directly influenced by sex steroids and their
      metabolites.

PMID- 12227901
TI  - Immunology and progestins in pregnancy.
AB  - The relationship between corpus luteum progesterone and rate of abortion is well
      known. Measurements of progesterone and clinical observations can demonstrate
      that low serum progesterone levels indicate, even better than human chorionic
      gonadotropin (hCG) measurements, an abnormal course of pregnancy. Early
      substitution seems to be the decisive therapeutic step. In relation to the
      concentration at the fetomaternal interphase progesterone leads to direct and
      indirect suppression of T-cell reactions. Progesterone acts synergistically with
      prostaglandin E2 immunosuppressive. Interleukin-2-induced cellular cytotoxicity
      is suppressed. Progesterone induces a number of proteins such as PP14, which
      inhibit the activity of T-cells and natural killer cells. Mitogenic lymphocyte
      reactivity is lowered. To date, results of immunological therapies do not prove
      the effectiveness of immunological treatment modalities.

PMID- 12227902
TI  - Laparoscopic antegrade continence enema (Malone) procedure: description and
      illustration of technique.
AB  - The antegrade continence enema (ACE Malone) procedure has improved the lives of
      many patients who struggle with intractable forms of constipation. We describe a
      laparoscopic approach to this technique and review the literature.

PMID- 12227903
TI  - Hand-assisted laparoscopic nephroureterectomy with cystoscopic en bloc excision
      of the distal ureter and bladder cuff.
AB  - Various hand-assisted and purely laparoscopic nephroureterectomy techniques have
      been described in the urologic literature. We describe a technique of hand
      assisted laparoscopic nephroureterectomy with cystoscopic en bloc excision of the
      distal ureter and bladder cuff that duplicates open surgical excision of these
      structures and obviates bladder trocar placement and midprocedural patient
      repositioning. The patient is placed in a modified dorsal lithotomy position with
      the tumor side elevated 30 degrees. Allen stirrups are utilized to allow
      simultaneous access to the urethra. A transperitoneal hand-assisted laparoscopic
      nephrectomy is performed. The technique is modified in that the ureter is clipped
      prior to the kidney dissection to avoid distal migration of tumor cells during
      kidney manipulation. After the kidney is isolated, the intact ureter is liberated
      distal to the intramural hiatus. The remaining dissection is completed
      intravesically under cystoscopic guidance. While the surgeon's intra-abdominal
      hand places the ureter on tension, the cystoscopist transurethrally excises the
      bladder cuff and intramural ureter with a Collings knife. The complete surgical
      specimen is removed en bloc through the hand port. The bladder is not closed. A
      urethral catheter connected to straight drainage remains until the seventh
      postoperative day, when a cystogram is performed; if it is normal, the catheter
      is removed.

PMID- 12227904
TI  - Laparoscopic radical cystectomy with urinary diversion: completely intracorporeal
      technique.
AB  - Laparoscopic radical cystectomy with urinary diversion performed using
      intracorporeal techniques exclusively is a new development in the growing field
      of minimally invasive urology. This report details step by step the completely
      intracorporeal laparoscopic technique of cystectomy, bilateral pelvic
      lymphadenectomy, and urinary diversion with creation of an ileal conduit or
      neobladder, including the isolation of ileum, restoration of bowel continuity,
      retroperitoneal transfer of the left ureter to the right side, bilateral stented
      ureteroileal anastomoses, and urethroileal anastomosis in case of orthotopic
      diversion. Although at present, this is still a technique in development at high
      volume medical centers, it holds promise as a minimally invasive yet
      appropriately radical form of treatment for patients with muscle-invasive bladder
      cancer. Definition of its true role awaits greater experience and long-term
      comparisons of the outcomes with those of traditional open surgery.

PMID- 12227905
TI  - Transutricular seminal vesiculoscopy.
AB  - Disorders of the seminal vesicle have been evaluated mainly via imaging
      techniques. We developed a technique to examine the interior of seminal vesicles
      endoscopically. In 37 hemospermic patients, transrectal ultrasound (TRUS) or
      endorectal MRI were performed preoperatively. When the patients had definite
      abnormalities on the imaging studies and did not improve after medication over a
      period exceeding 3 months, transutricular seminal vesiculoscopy was performed
      using a 6F or a 9F rigid ureteroscope. Patients were then followed for at least 3
      months. Endoscopic evaluation was also performed in two patients with stage B(1)
      and D(2) prostate carcinoma. In hemospermic patients, hemorrhage was found in the
      seminal vesicles or the ejaculatory ducts in 23 (62.2%) and 3 (8.1%),
      respectively. Calculi were present in the seminal vesicles or ejaculatory ducts
      in 6 (16.2%) and 2 (5.4%), respectively. In prostate carcinoma patients, seminal
      vesiculoscopy was similarly informative. Postoperative complications, including
      epididymitis or retrograde ejaculation, were not observed. Transutricular seminal
      vesiculoscopy can be performed easily with conventional endoscopic equipment and
      provides useful information.

PMID- 12227906
TI  - Trends in endourologic practice.

PMID- 12227907
TI  - Controversial cases in endourology.

PMID- 12227908
TI  - Salvage extracorporeal shockwave lithotripsy after failed distal ureteroscopy.
AB  - BACKGROUND AND PURPOSE: When intervention is necessary, controversy remains as to
      the best treatment modality for stones of the distal ureter. In general,
      ureteroscopy is favored over extracorporeal shockwave lithotripsy (SWL) as the
      treatment of choice for distal ureteral stones. Although uncommon, ureteroscopy
      failures have traditionally necessitated repeat ureteroscopy to retrieve retained
      stone fragments. We evaluated the efficacy of salvage SWL for failed primary
      distal ureteroscopy in the community setting. PATIENTS AND METHODS: From December
      1989 to December 2000, 6099 patients underwent SWL with the Dornier HM4
      lithotripter at our institution. We retrospectively identified 31 patients who
      had undergone the SWL after a failed distal ureteroscopy. RESULTS: The average
      stone size in these patients was 9.4 mm, the average time interval from
      ureteroscopy to SWL was 17.2 days, and the average number of shockwaves delivered
      was 2386. All patients had had stents placed after ureteroscopy. Twenty-seven
      patients (87%) had resolution of their stone burden after one SWL session. The
      remaining four patients underwent additional procedures. CONCLUSIONS:
      Ureteroscopy is an effective modality for the treatment of distal ureteral
      stones. However, when unsuccessful, a salvage procedure may be necessary.
      Extracorporeal lithotripsy is a less invasive procedure with comparable success
      rates in the distal ureter. This report suggests that salvage SWL is an
      appropriate option for patients in whom distal ureteroscopic stone extraction
      fails.

PMID- 12227909
TI  - The high intra-abdominal testis: technique and long-term success of laparoscopic
      testicular autotransplantation.
AB  - BACKGROUND AND PURPOSE: Treatment of the high intra-abdominal testis is often a
      challenging problem. We present our technique of and results with
      laparoscopically assisted testicular autotransplantation (LATA) for treatment of
      the high intra-abdominal testis. PATIENTS AND METHODS: We reviewed the medical
      records of 15 patients with a high intra-abdominal testis who underwent
      procedures between 1993 and 1999 in which intra-abdominal dissection and
      testicular mobilization was performed laparoscopically. The LATA technique is
      described. RESULTS: The 15 patients underwent 17 LATA procedures. Age at surgery
      ranged from 6 months to 13 years (mean 3.6 years; median 2.5 years). Two of these
      patients had undergone failed contralateral orchidopexy for an intra-abdominal
      testis, and two patients underwent metachronous bilateral procedures. The
      laparoscopic dissection and microvascular anastomoses were successful in all
      patients. There were no postoperative complications. The involved testis remained
      viable with adequate growth in 15 of 17 procedures (88%) during a median 42-month
      (range 7-70 months) follow-up. Successful procedures included those in the two
      patients with contralateral atrophic testes and the two who underwent bilateral
      procedures. CONCLUSIONS: The LATA demonstrated a good long-term surgical outcome
      and may be the technique of choice in patients with bilateral intra-abdominal
      testes or patients who have contralateral testis atrophy following unsuccessful
      orchidopexy.

PMID- 12227910
TI  - Laparoscopy for definite localization and simultaneous treatment of ectopic
      ureter draining a dysplastic kidney in children.
AB  - BACKGROUND AND PURPOSE: Single-system ectopic ureter draining a dysplastic kidney
      is a rare urologic abnormality. In this study, we evaluated our own experience
      using laparoscopy for the simultaneous identification and removal of such
      ureterorenal units. PATIENTS AND METHODS: Between February 1999 and August 2001,
      four girls with a mean age of 11 years presented with urinary incontinence. After
      imaging studies including CT scan, MRI, or both were done, all the patients
      underwent laparoscopy for definitive localization and simultaneous treatment.
      RESULTS: In all cases, ultrasonography and intravenous urography combined to
      reveal a single normal kidney. Even the CT scan could not identify the dysplastic
      kidney or ectopic ureter in three children. Laparoscopy was performed
      transperitoneally in all four patients, and a small dysplastic kidney was
      identified. Discovery of the kidney was not difficult because we initially
      identified the ureter crossing over the iliac vessels. Laparoscopic
      nephroureterectomy was successful in all patients with a mean operative time of
      102 minutes. There was no significant intraoperative or postoperative
      complication, and the mean postoperative hospital stay was 2.5 days. All patients
      have remained completely dry without any problems after surgery. CONCLUSIONS: For
      patients having a clinical suspicion of ectopic ureter draining a dysplastic
      kidney, laparoscopy may represent an alternative modality for simultaneous
      diagnosis and treatment.

PMID- 12227911
TI  - Posterior retroperitoneoscopic partial nephrectomy using microwave tissue
      coagulator for small renal tumors.
AB  - BACKGROUND AND PURPOSE: Laparoscopic partial nephrectomy remains surgically
      challenging because of the potential for excessive blood loss, infection, and the
      development of urinary fistulas. In addition, posterior retroperitoneoscopic
      partial nephrectomy is not popular because of the limited space for surgical
      manipulation. We evaluated the usefulness of a microwave tissue coagulator in
      posterior retroperitoneoscopic partial nephrectomy for small posterior renal
      tumor. PATIENTS AND METHODS: Posterior retroperitoneoscopic partial nephrectomy
      was performed without renal pedicle clamping using a microwave tissue coagulator
      in six patients with small posterior renal tumors. RESULTS: The mean operative
      time was 136 minutes (range 78-180 minutes), and the blood loss was <20 mL. No
      serious operative complications occurred, and there was no significant
      deterioration of renal function. CONCLUSION: Posterior retroperitoneoscopic
      partial nephrectomy using a microwave tissue coagulator can be a safe and less
      invasive method for the treatment of small posterior renal tumors.

PMID- 12227912
TI  - Laparoscopic transperitoneal adrenalectomy using a remote-controlled robotic
      surgical system.
AB  - BACKGROUND AND PURPOSE: Laparoscopic adrenalectomy is considered the standard
      method for removal of benign adrenal tumors. Although laparoscopic surgery
      provides clear patient benefit, laparoscopic adrenalectomy using conventional
      instrumentation is complex. Our objective was to evaluate whether the da Vinci
      trade mark Surgical System, a comprehensive robotic endoscopic surgical device,
      could be used effectively to perform laparoscopic adrenalectomy. PATIENTS AND
      METHODS: Through a transperitoneal approach, three right and one left adrenal
      tumors were removed in four patients using this method. RESULTS: There were no
      complications, and the clinical results were excellent. CONCLUSION: We
      demonstrate the feasibility of performing laparoscopic adrenalectomy exclusively
      by using robotic telepresent technology from a remote workstation. The da Vinci
      System enables conventionally trained urologic surgeons to perform complex
      minimally invasive procedures with ease and precision. Therefore, we are
      convinced that the system helps the urologist to adapt the whole spectrum of
      laparoscopic procedure in this field.

PMID- 12227913
TI  - Laparoscopic radical cystectomy with orthotopic neobladder.
AB  - PURPOSE: We report our technique of laparoscopic radical cystectomy in nine
      patients. Diversion was achieved by a modified Camey II orthotopic neobladder
      (the Y bladder) performed by a minilaparotomy in three cases and laparoscopically
      in the last six cases. PATIENTS AND METHODS: There were eight men with muscle
      invasive transitional-cell carcinoma and one woman with verrucous squamous-cell
      carcinoma of the bladder. The age range was 41 to 65 years. The control of the
      posterior and lateral bladder pedicles was achieved by vascular Endo-GIA in the
      first three cases and by the 10-mm Harmonic Shears (Ultracision; Ethicon) in the
      last six cases. The operative specimen was extracted through a 3- to 5-cm muscle
      splitting incision in the right iliac fossa. The detubularized pouch was prepared
      extracorporeally through the same incision. The urethral and ureteral anastomoses
      were performed using laparoscopic intracorporeal suturing in the last six cases.
      RESULTS: The operative time ranged from 6.5 to 12 hours (median 8.3 hours). The
      blood loss was 150 to 500 mL. Oral feeding was resumed on the 3rd postoperative
      day. The stents were usually removed on the 8th postoperative day. A pouchogram
      was obtained on the 10th postoperative day, and the urethral catheter was
      removed. The lymph nodes as well as the surgical margins were tumor free.
      CONCLUSION: Laparoscopic radical cystectomy and orthotopic neobladder creation is
      feasible, although difficult and technically demanding. The use of the Harmonic
      Shears in the cystectomy reduces the operative cost significantly. With growing
      experience, laparoscopic radical cystectomy and continent urinary diversion can
      be an alternative to the open technique.

PMID- 12227914
TI  - Lateral decubitus position for percutaneous nephrolithotripsy in the morbidly
      obese or kyphotic patient.
AB  - BACKGROUND AND PURPOSE: Morbidly obese or debilitated patients do not tolerate
      the prone position used for percutaneous nephrolithotripsy (PCNL) well and may
      suffer from severe cardiorespiratory compromise in this position. The purpose of
      this study is to demonstrate a simple way to overcome this difficulty. PATIENTS
      AND METHODS: Two morbidly obese patients, ages 48 and 32 years, with Body Mass
      Indices of 47.5 and 43.2 and a 68-year old patient severely debilitated by
      multiple cerebral infarctions, ischemic heart disease, and kyphosis suffered from
      relatively high renal stone burdens. For PCNL, the patients were placed in the
      lateral decubitus position. To obtain an anteroposterior projection in this
      position, the C-arm fluoroscopy unit was tilted to one side and the operating
      table to the other. Tract dilation, stone fragmentation, and fragment extraction
      were performed with the patient in this position. RESULTS: An attempt to perform
      PCNL in the prone position in the first patient was aborted because of severe
      hypoxemia and hypercarbia. In the lateral decubitus position, the procedures were
      easily performed in all patients without any complications. It was noted that by
      rotating the C-arm to a perpendicular position, it was possible to perform
      nephroscopy and use fluoroscopy simultaneously. CONCLUSION: We highly recommend
      using the lateral position for PCNL in morbidly obese patients and in patients
      suffering from kyphosis. This position is safe and convenient.

PMID- 12227915
TI  - Interstitial laser coagulation combined with minimal transurethral resection of
      the prostate for the treatment of benign prostatic hyperplasia.
AB  - BACKGROUND: Transurethral resection of the prostate (TURP) represents the gold
      standard in the surgical treatment of benign prostatic hyperplasia (BPH).
      However, this method still has significant morbidity mainly associated with
      irrigation fluid absorption and blood loss. PATIENTS AND METHODS: A combination
      of interstitial laser coagulation (ILC) with limited TURP was established to
      reduce specific risks of transurethral resection and was applied in 41 patients
      with bladder outlet obstruction caused by BPH. In these patients, a subtotal
      resection of the prostate was not possible because of anesthesiologic risk
      factors. After insertion of a suprapubic catheter, ILC was performed under visual
      control using an Nd:YAG laser followed by resection of the bladder neck or the
      median lobe. Isotonic carbohydrate solution with 1% ethanol was used for
      irrigation, and irrigation fluid uptake was quantified by measurements of the
      ethanol concentration in the patients' exhaled breath. Additional measures such
      as blood loss, need for blood transfusions, and operative time were evaluated.
      RESULTS: The operations were performed without major complications with a mean
      operative time of 35 +/- 11 minutes for the entire procedure. An irrigation fluid
      uptake of 9 +/- 32 mL and no TUR syndrome were observed. The mean blood loss was
      minimal with a change in the hemoglobin of -1.3 +/- 1.1 g/dL and no need for
      blood transfusions. CONCLUSION: These results demonstrate that ILC with
      subsequent minimal TURP is an applicable method in the surgical treatment of BPH
      with reduction of blood loss and of the risk of TUR syndrome. This procedure may
      help to reduce the morbidity of TURP, especially in high-risk patients.

PMID- 12227916
TI  - Stone research on the bench: where we are and where we are going.

PMID- 12227918
TI  - Aging: the fitness-stress continuum and genetic variability.
AB  - Assuming the stress theory of aging, longevity depends upon primary selection for
      stress resistance and metabolic efficiency. Predominantly based upon experimental
      studies in the insect Drosophila melanogaster, high genetic variability for
      fitness, especially mortality, occurs under extreme stress. Isofemale strains
      derived from the progeny of recently collected single inseminated Drosophila
      females from the wild should provide useful biological material for extrapolating
      to quantitative genetic studies in man. Furthermore, environments from the benign
      (hormetic) to the extreme can be incorporated. Survival to old age may depend
      upon genes for metabolic efficiency that respond to the environmental challenges
      of living as limits to adaptation are approached. Under this scenario the
      survival of longevity mutants in man to ages analogous to the extreme life spans
      found in some experimental organisms under benign or protected laboratory
      conditions is unlikely. More future emphasis is needed on genetic variation of
      longevity in natural populations of experimental organisms under an array of
      realistically stressful environments to act as an evolutionary model for
      longevity in our own species.

PMID- 12227919
TI  - The complex genetic architecture of Drosophila life span.
AB  - Continuous phenotypic variation in life span results from segregating genetic
      variation at multiple loci, the environmental sensitivity of expression of these
      loci, and the history of environmental variation experienced by the organism
      throughout its life. We have mapped quantitative trait loci (QTL) that produce
      variation in the life span of mated Drosophila melanogaster using a panel of
      recombinant inbred lines (RIL) that were backcrossed to the parental strains from
      which they were derived. Five QTL were identified that influence mated life span,
      three were male-specific, one was female-specific, and one affected life span in
      both sexes. The additive allelic effects and dominance of QTL were highly sex
      specific. One pair of QTL also exhibited significant epistatic effects on life
      span. We summarize all of the QTL mapping data for Drosophila life span, and
      outline future prospects for disentangling the genetic and environmental
      influences on this trait.

PMID- 12227920
TI  - Sociocultural influences in genetic designs of aging: unexplored perspectives.
AB  - As the aging population continues to become more diverse, there is growing
      interest in understanding the similar and unique aspects of aging within and
      across people of different ethnic groups. The impact of culture on the sources of
      variation identified in quantitative genetic approaches has not been well
      discussed in the literature. The purpose of this paper is to review previous
      research pertinent to the cultural aspects of quantitative genetic approaches and
      methodologies, and provide conceptual and statistical approaches for advancing
      the science. To meet this objective, results from previously published studies as
      well as preliminary data analyses from the Carolina African American Twin Study
      of Aging will be presented. There are three themes to draw from the issues
      discussed in this paper: (1) avoiding genetic reductionism, (2) interpreting
      differential heritabilities, and (3) modeling cultural influences.

PMID- 12227921
TI  - Sources of influence on rate of cognitive change over time in Swedish twins: an
      application of latent growth models.
AB  - The use of latent growth models to examine influence on individual differences on
      ability level versus rate of change were examined for measures of fluid ability,
      memory, and perceptual speed in a sample of twins from the Swedish Adoption/Twin
      Study of Aging. Results indicated a larger amount of individual variation for
      average ability level (i.e., intercept) than rate of change (i.e., slope) for all
      three traits: Block Design, Thurstone's Picture Memory, and Symbol Digit.
      Generally, genetic influences were of greater importance to individual variation
      in ability level whereas variation for rate of change exhibited a larger
      environmental component. These findings support theories of increasing
      environmental influences with age. When genetic and environmental sources of
      covariation between educational attainment and pulmonary function with latent
      growth parameters were considered, the sources of covariation between the latent
      cognitive growth model parameters (i.e., intercept and slope) and both covariates
      were primarily genetic for ability level (intercepts) but environmental for rate
      of change (slopes). Such findings suggest that the forces important to timing or
      entry into cognitive decline may reflect stochastic processes or external
      environmental factors, primarily nonshared, that may differentially hasten
      cognitive decline in twins. These same forces may overlap with those that
      influence higher or lower educational attainment or those leading to better or
      worse pulmonary functioning.

PMID- 12227922
TI  - The heritability of level and rate-of-change in cognitive functioning in Danish
      twins aged 70 years and older.
AB  - To investigate heritable influences on overall level and rate-of-change in
      cognitive ability, biometric growth models were fit to cognitive data from nearly
      1000 Danish twins age 70 years and older. Twins are participants in the ongoing
      Longitudinal Study of Aging Danish Twins, a cohort-sequential study of twins
      assessed every 2 years for up to four waves. Cognitive ability was assessed by
      five brief cognitive tasks: a fluency measure, forward and backward digit span,
      and immediate and delayed list recall. Model-fitting results indicated that
      although the overall level of cognitive functioning was highly heritable (h(2) =
      .76, 95% confidence interval of .68 to .82), the rate of linear change was not
      (h(2) = .06, 95% confidence interval of .00 to .57). These findings suggest that
      the search for specific genes might reasonably focus on average level of
      cognitive performance, whereas specific environmental influences might account
      for cognitive change.

PMID- 12227923
TI  - Genetics of behavioral aging: animal models and the human condition.
AB  - Animal models have played an important role in elucidating the nature of aging
      processes in general, and of behavioral aging specifically. Both aging and the
      behavioral processes of interest in this context are manifestly complex. Recent
      scholarship focusing on the nature of systems has provided new and varied
      conceptual schemata for addressing such intricacy. In this report, animal model
      systems are viewed in relation to some elementary systems notions. Limitations of
      the prototypical animal model are discussed, with particular emphasis on the
      implications of gene-gene and gene-environment interactions. These same
      interactions also provide opportunities. The traditional methods of genetic
      manipulation and control, combined with the powerful new tools of molecular
      genetics, and informed by systems considerations, offer broadened research
      horizons.

PMID- 12227924
TI  - A multistate model of the genetic risk of Alzheimer's disease.
AB  - The risk of Alzheimer's disease (AD) increases rapidly with age. It is not clear
      whether this increase continues at the very oldest ages. A slowing of the rate of
      increase in risk could result from heterogeneity associated with genetic or other
      risk factors. This study models explicitly the effect of heterogeneity of risk on
      the age pattern of incidence of AD. The model is fitted to published data from
      five prevalence studies and nine studies of AD risk by genotype for the
      apolipoprotein-E (APOE) gene. The model suggests that the prevalence of AD among
      white males at age 100 is 41.5%. Heterogeneity in the risk of AD causes the
      incidence rate to level off at about 11.7% per year at age 102. Some of the
      heterogeneity of risk is due to differences by APOE genotype. The model estimates
      that at age 80, the epsilon3/4 genotype is associated with an incidence rate 3.40
      times that of those with the epsilon3/3 genotype. The epsilon4/4 genotype is
      associated with a relative risk of 9.4. Carriers of the epsilon2 allele have a
      risk that is only 43% of the risk among the epsilon3/3. There is substantial
      variation in risk associated with unobserved risk factors. Within each APOE
      genotype, the coefficient of variation of risk is about 1.09. In addition, the
      model estimates that about 0.20% of the population carries genes that cause AD at
      very early ages, through mechanisms that are not associated with the APOE
      genotype.

PMID- 12227925
TI  - Hyperthermic teratogenicity, thermal dose and diagnostic ultrasound during
      pregnancy: implications of new standards on tissue heating.
AB  - Hyperthermia is a recognized teratogen in mammalian laboratory animals and is a
      suspected teratogen for humans. The purpose of this synopsis is to reanalyse
      existing data on hyperthermia-induced teratogenic effects in experimental
      mammalian systems in terms of a thermal dose (temperature:time) concept, and then
      to illustrate the utility of this concept to human situations involving potential
      thermal increments to post-implantation embryos and foetuses. For example, the
      threshold temperature elevation for hyperthermia-induced teratogenic effects in
      experimental mammals is estimated (but not rigorously tested) to be approximately
      1.5 degrees C above core values for exposures of long duration, possibly with a
      thermal dose of approximately 5 min duration or more at 4 degrees C. This level
      of tissue temperature increment is within the capability of some modern
      diagnostic ultrasound (DUS) devices sold within the USA and abroad.
      Epidemiological studies have not indicated any hazard from the use of DUS, but
      such studies are limited in sensitivity and were conducted with DUS devices whose
      acoustic outputs were relatively low compared to those presently available. After
      a regulatory change that allowed for substantially increased acoustic outputs,
      modern DUS devices were mandated to provide the user with on-screen information
      (the Thermal Index, or 'TI') about ultrasound-induced temperature increments in
      the target tissue. The TI is generally accurate to within a factor of 2, but the
      factor may be as high as 6 in certain obstetric settings. Thus, informed use of
      and attention to the TI is strongly advised, with this admonition gaining
      increased emphasis if the present regulations regarding allowable acoustic
      outputs of DUS devices were to be further relaxed or eliminated.

PMID- 12227926
TI  - Radiosensitization of heat resistant human tumour cells by 1 hour at 41.1 degrees
      C and its effect on DNA repair.
AB  - The present study was undertaken to determine if short duration (1-2 h), moderate
      hyperthermia (41.1 degrees C) could radiosensitize human tumour cells. It was
      found that moderate hyperthermia (41.1 degrees C), for as little as 1 h, can
      radiosensitize heat resistant human adenocarcinoma cells, NSY42129 (NSY),
      provided the cells are irradiated 15 min prior to the end of the heat exposure.
      Analysis of the survival data showed a 2.5-3-fold increase in the alpha parameter
      with no significant change in the beta parameter of the survival curve, implying
      that the cells had become more susceptible to killing by single radiation energy
      deposition events as opposed to lethal events that require an interaction between
      two separate energy deposition events. 41.1 degrees C hyperthermia did not affect
      the induction or repair of alkaline labile DNA damage in a way that correlated
      with radiosensitivity. In contrast, heat-induced changes in the induction of
      micronuclei by radiation correlated with changes in cell killing. Therefore, the
      effect of 41.1 degrees C hyperthermia on the intracellular localization of the
      DNA double strand break repair protein, Mre11, was measured using in situ
      immunofluorescence and immunoblotting of soluble and insoluble cellular
      fractions. The results showed that Mre11 delocalizes from the nucleus as a
      function of time at 41.1 degrees C. It was then determined if 41.1 degrees C
      hyperthermia altered the association of Mre11 with its functional partner, Rad50.
      A significant decrease in the amount of Rad50 recovered with Mre11 occurred under
      the experimental conditions that produced significant radiosensitization. These
      results are consistent with the possibility that the heat-induced perturbation in
      Mre11 localization and its radiation-induced association with Rad50 contributes
      to an increase in radiosensitivity.

PMID- 12227928
TI  - Theoretical investigation of measurement procedures for the quality assurance of
      superficial hyperthermia applicators.
AB  - This work presents the results obtained from simple numerical models concerning
      the measurement uncertainty with thermographic techniques used for the evaluation
      of superficial hyperthermia applicators. Based upon the calculations performed,
      it is shown that, when using a thermographic technique to measure the SAR
      distribution of an applicator, heating times from 60-120s and measuring times of
      10s are acceptable for an accurate assessment of the half-width at half power
      (HWHP) of an applicator (error less than 2%) with an expected HWHP larger than
      2.5 cm. Only when the HWHP is expected to be less than 2.5 cm does the heating
      time need to be adapted to obtain an accuracy of 2% or better. For the assessment
      of the maximum SAR, the situation is worse. Even with a careful experimental
      design, it is difficult to measure the maximum SAR with an error less than 7%.

PMID- 12227927
TI  - Acute extracellular acidification increases nuclear associated protein levels in
      human melanoma cells during 42 degrees C hyperthermia and enhances cell killing.
AB  - Acute acidification is being investigated as a strategy to sensitize human
      melanoma to 42 degrees C hyperthermia. The present study was conducted to
      determine the effect of hyperthermia and acute extracellular acidification on the
      nuclear associated protein (NAP) levels, heat shock protein (hsp) 70 and hsp27
      content, and cell survival of human melanoma cells cultured at pH 7.3 or pH 6.7.
      It was observed that NAP levels increased slightly in both populations after 2 h
      of heating and then decreased to control levels with increasing time of heating
      at the growth pH. However, the NAP levels continued to increase in cells acutely
      acidified to pH 6.3 prior to and during heating. Hsp70 was induced to comparable
      levels in cells heated at their growth pH; however, the hsp27 levels were greater
      in cells cultured and heated at pH 6.7 than in cells cultured and heated at pH
      7.3. Acute acidification to pH 6.3 prior to and during heating suppressed the 42
      degrees C induction of hsp70 and hsp27 in both cell populations. The melanoma
      cells cultured and heated at pH 6.7 were more resistant to cell killing than
      cells cultured and heated at pH 7.3. Both populations were sensitized to cell
      killing by acute acidification to pH 6.3. The results suggest that hsps induced
      during 42 degrees C treatment associate with aggregating NAPs, enhancing their
      detergent solubility, and that abrogation of induced expression of hsps during
      heating at pH 6.3 contributes to increased levels of insoluble NAPS. In
      conclusion, acute extracellular acidification inhibits 42 degrees C induction of
      hsps, increases NAP levels, and decreases cell survival in DB-1 human melanoma
      cells.

PMID- 12227929
TI  - An edge-element based finite element model of microwave heating in hyperthermia:
      method and verification.
AB  - Hyperthermia has been shown to improve local tumour control of superficial and
      deep seated lesions when combined with radiotherapy. There remains difficulty in
      heating larger tumours with conventional applicators, but this is being addressed
      by several new applicator designs. This paper presents a new numerical model of
      microwave heating which is designed to aid in the development of new applicators
      for superficial heating. The model is based on a finite element method which
      utilises vector valued basis functions instead of the more conventional scalar
      valued basis functions. These basis functions were chosen since they are
      inherently suited for the solution of Maxwell's equations due to their vector
      nature. The model was successfully verified against an analytic solution to the
      Mie scattering problem as well as against previously published measurements of
      heating from a modified water bolus attached to a conventional waveguide
      applicator. An accompanying paper describes an application of this model to the
      design optimization of this modified bolus.

PMID- 12227930
TI  - An edge-element based finite element model of microwave heating in hyperthermia:
      application to a bolus design.
AB  - Heating of superficial tumours with microwave waveguide applicators has been
      shown in phase III trials to significantly improve the local control of small
      lesions when combined with radiation therapy. This success has not yet translated
      to the treatment of larger tumours, due to difficulty in adequately heating the
      entire tumour region. Several modifications to the water bolus used with external
      waveguide applicators have been made in the past in order to increase the heating
      area. One such modification consisted of a large, microwave-absorbing patch
      placed inside the bolus, which flattens out the beam profile produced by the
      applicator. Using this bolus instead of a conventional one resulted in a 30%
      increase in the effective heating volume produced by the BSD MA120 applicator.
      This paper describes an optimization procedure for this bolus design which
      utilises a new finite element model of microwave heating described in an
      accompanying paper. The optimization procedure resulted in a further 28% increase
      in the effective heating volume.

PMID- 12227931
TI  - Performance and use of current sheet antennae for RF-hyperthermia of a phantom
      monitored by 3 tesla MR-thermography.
AB  - Several MR-compatible current sheet antennae (CSA) of different height (h) (16 cm
      (l) x 8 cm (w) x 1-5 cm (h)) were built for simulated RF (96 MHz) hyperthermia of
      a medium-sized (12l) tissue-equivalent phantom inside a 3 tesla whole body
      tomograph. Prior to use, efficiencies of the CSA were determined by network
      analysis and by calorimetry. Depending on the height h of the CSA and on the
      thickness d(bolus) of the water bolus used for RF-coupling of the CSA to the
      lossy medium, their efficiency varied between 20-70% and the CSA with h = 3 cm
      was selected for simulated RF hyperthermia. During heating, spatial temperature
      distributions (20-42 degrees C) of five slices (voxel size 2 x 2 x 10mm(3)) were
      recorded intermittently within 4 s/slice by measuring the temperature dependent
      shift of the (1)H resonance frequency (125.32 MHz). A phased array consisting of
      two identical CSA produced distinctly different spatial temperature distributions
      at 0 and 180 degrees phase difference between both RF channels feeding the
      antennae. Within a one-dimensional heat diffusion model, the specific absorption
      rate (SAR) of the electromagnetic wave generated by a single antenna was deduced
      from the experimental data resulting in a penetration depth (1/e(2)) of
      approximately 4 cm.

PMID- 12227932
TI  - Effect of hyperthermia combined with external radiation therapy in primary non
      small cell lung cancer with direct bony invasion.
AB  - PURPOSE: Local control in lung cancer directly invading the bone is extremely
      poor. Effects of regional hyperthermia combined with conventional external beam
      radiation therapy were evaluated. MATERIALS AND METHODS: Thirteen patients with
      non-small lung cancer (NSCLC) with direct bony invasion were treated with
      hyperthermia plus irradiation (hyperthermia group). The treatment outcome was
      compared with the historical treatment results in 13 patients treated with
      external radiation therapy alone (radiation alone group). In patients with no
      distant metastasis, radiation therapy at a total dose of 60-70 Gy was
      administered to both groups. Hyperthermia was performed for 45-60 min immediately
      after irradiation for two-four sessions with radiofrequency capacitive heating
      devices. RESULTS: For primary response, 10 of the 13 tumours responded to the
      treatment (3 CR, 7 PR) in the hyperthermia group, whereas seven tumours responded
      (1 CR, 6 PR) in the radiation alone group. The 2-year local recurrence-free
      survival rate for clinical M(0) patients in the hyperthermia group and that in
      the radiation alone group were 76.1 and 16.9%, respectively. Three patients died
      of distant metastases within 2 years in the hyperthermia group, but two out of
      three tumours histologically disappeared, even in the autopsy examination. The 2
      year overall survival rate for clinical M(0) patients in the hyperthermia group
      and that in the radiation alone group were 44.4 and 15.4%, respectively. No
      severe pulmonary complication was observed in either group. CONCLUSIONS: Regional
      hyperthermia combined with conventional irradiation could be a tool to improve
      local control in patients with NSCLC deeply invading the chest wall.

PMID- 12227933
TI  - Correction of analytical results for recovery: a comparison of the method
      performance characteristics from recent collaborative trials studies for
      aflatoxin quantification using conventional and robust statistics.
AB  - Results from recently conducted collaborative trials on the determination of
      aflatoxin B(1) in various matrices have been evaluated to establish whether the
      use of recovery data would result in a distinct change of the relative between
      laboratory standard deviation (RSD(R)) of the corrected data compared with the
      uncorrected data. In addition, we applied conventional and robust statistics to
      evaluate whether the impact of the use of recovery data on the estimation of
      RSD(R) depended on the statistical method applied for data analysis. This
      investigation was based on means before and after correction for recovery. The
      method performance characteristics were calculated using results from naturally
      contaminated test materials, while the results from test materials fortified with
      the target analytes were used to estimate the recovery. The study revealed that
      applying conventional and robust statistics in general led to comparable
      estimates for RSD(R). The comparison about the use of recovery data showed that
      in most cases, the RSD(R) obtained from the analysis of aflatoxin B(1) decreased
      after correction of the results for recovery. This tendency was similar when the
      comparison was done using robust or conventional statistics. However, in three
      cases, conventional statistics yielded a higher RSD(R) for the corrected data,
      whereas robust statistics showed the opposite. Looking carefully at the data, the
      treatment of conventional statistics indicated that the way outliers are detected
      and removed could result in an under- or overestimation of RSD(R). Applying the
      law of error propagation revealed that most likely the correlation between the
      uncorrected data and the recovery rate led to a reduced variability of the data
      corrected for recovery.

PMID- 12227934
TI  - Fluoride exposure of East African consumers using alkaline salt deposits known as
      magadi (trona) as a food preparation aid.
AB  - The fluoride content of Tanzanian and Kenyan magadi has been estimated to be in
      the range 0.1-17.9 mg F(-) g(-1), which is comparable with that reported
      elsewhere, but indicating a considerable variation in levels. The median fluoride
      content of crystalline magadi harvested from the alkaline lakes was 2.1 mg g(-1),
      which was higher than the median of 1.4 mg g(-1) for scooped magadi harvested
      from the surface soil. The highest median fluoride contents of 3.2 and 2.9 mg g(
      1) were found in magadi originating from Lake Magadi, Kenya, and Lake Natron,
      Tanzania, respectively. It was found that the fluoride content varied
      significantly even for magadi originating from the individual lake, e.g. the
      fluoride content in magadi from Lake Magadi was between 0.1 and 8.7 mg g(-1). In
      a lump of magadi originating from Lake Magadi, it was found that the fluoride
      content in 20 smaller part samples was subject to considerable variation
      indicating that the fluoride-bearing minerals were unevenly distributed in the
      lump. Results show that the fluoride is mainly present in grains <1.0 mm that
      made up 25% of the magadi sample. When daily eating the popular meal makande as
      in Tanzania, the exposure to fluoride through magadi in 70% of cases was
      estimated to be <4 mg per adult day(-1), as recommended by the WHO. Thus, the
      health hazard from magadi-fluoride is estimated to be significant in cases where
      the magadi is heavily contaminated.

PMID- 12227935
TI  - Total and methylmercury residues in tuna-fish from the Mediterranean sea.
AB  - This study was carried out to determine the current levels of total mercury and
      methylmercury in the muscle tissue of albacore (Thunnus alalunga) and bluefin
      tuna (Thunnus thynnus) caught in the Mediterranean sea with the purpose of
      ascertaining whether the concentrations exceeded the maximum level fixed by the
      European Commission Decision. Total mercury concentrations ranged from 0.84 to
      1.45 mg kg(-1) w.w. (av. 1.17 mg kg(-1) w.w.) and from 0.16 to 2.59 mg kg(-1)
      (av. 1.18 mg kg(-1) w.w.) in the muscle of albacore and bluefin tuna,
      respectively. In 78.6% of albacore and in 61.1% of bluefin tuna analysed, total
      mercury concentrations exceeded the maximum level fixed by the European
      Commission Decision (Hg = 1 micro g g(-1) wet wt). In the two species, mercury
      was present almost completely in the methylated form, with percentages between 77
      and 100% (av. 91.3%) in albacore and between 75 and 100% (av. 91%) in bluefin
      tuna. In order to assess the potential health impact, the estimated weekly intake
      was calculated. The estimated weekly intake was far above the established
      Provisional Tolerable Weekly Intake for both species.

PMID- 12227936
TI  - Survey of bottled drinking waters sold in Canada for chlorate, bromide, bromate,
      lead, cadmium and other trace elements.
AB  - Mineral, spring and other bottled drinking waters sold in Canada in the winter of
      1995-96 were surveyed for chlorate, bromide, bromate, Cr(VI), Li, B, Al, Mn, Cu,
      Zn, Sr, Ba, Be, V, Cr, Co, Ni, As, Se, Mo, Ag, Cd, Sb, Tl, Pb, Na, K, Ca and Mg.
      Chlorate and bromide were determined by ion chromatography (IC) with conductivity
      detection, Cr(VI) by IC with colorimetric detection, bromate by solvent
      extraction and gas chromatography (GC), trace elements by inductively coupled
      plasma mass spectrometry (ICPMS), and Na, K, Ca and Mg by flame atomic absorption
      spectrometry (FAA). Most chemicals in the 199 samples analysed were well within
      national and international drinking water guidelines. World Health Organization
      and/or Canadian drinking water guidelines were exceeded for B (22 samples), Al
      (9), Cr (1), Mn (5), Ni (1), As (10), Se (24) and Pb (1). Bromate levels are
      reported for information purposes and are considered as the maximum
      concentrations in the samples. In three distilled water products, unexpectedly
      high concentrations of Cu (88-147 micro g l(-1)) and Ni (16-35 micro g l(-1))
      were found, and a comparison of distilled and non-distilled waters from two of
      the brands suggested the likely cause to be contamination during the distillation
      process. Li concentration in one sample was at a therapeutic dose and could pose
      an overdose risk to individuals on Li medication.

PMID- 12227937
TI  - Unit-to-unit variability of pesticide residues in fruit and vegetables.
AB  - Pesticide residue levels (36 pesticides and some of their metabolites) were
      determined in the individual units taken from large samples of apples, bananas,
      celery, kiwi fruit, oranges, peaches and nectarines, pears, plums, potatoes, and
      tomatoes. The 65 large samples (generally about 100-110 units, but only 45 units
      of celery) were purchased at retail or wholesale outlets in the UK. The lots from
      which the samples were drawn originated from 17 different countries. Average
      concentrations in the samples were in the approximate range 0.002-2 mg kg(-1).
      Unit-to-unit variability factors (97.5th percentile mg kg(-1)/average mg kg(-1)),
      for the pesticide/product combination data sets in which >10% of samples
      contained measurable residues (n = 106), were in the range 1.4-9.6 (11.1 based on
      a value of zero for data below reporting limits). Analytical variance contributed
      only a small proportion (up to 11%) to the overall variance of the 106 data sets.
      There was no evidence of a relationship between the variability factor and the
      commodity, country of origin, residue concentration or the physicochemical
      characteristics of the pesticide. The extent of variability appears to be
      determined at or about the time of pesticide application. Taking non-detectable
      residues as half the reporting limits, the frequency distribution of variability
      factors was approximately log-normal, with a geometric mean of 3.4. The
      corresponding 95% probability limits of the variability factors were calculated
      to be 1.6 and 7.6.

PMID- 12227938
TI  - Identification and occurrence of the bioactive beta-carbolines norharman and
      harman in coffee brews.
AB  - Norharman and harman, two heterocyclic beta-carboline alkaloids with biological
      activity, were found in brewed coffee. Identification and analysis were carried
      out by HPLC-MS and RP-HPLC-fluorescence, respectively. All tested samples of
      brewed coffee including ground coffee, decaffeinated coffee, instant coffee and
      espresso contained both norharman and harman in variable amounts. Norharman was
      the major beta-carboline alkaloid in brewed coffee at levels up to 9.34 microg g(
      1) in instant ground coffee compared with harman, which had levels up to 1.67
      microg g(-1). The two beta-carbolines appeared to be formed during roasting of
      the coffee beans. It is concluded that drinking coffee is a major exogenous
      dietary source of these bioactive beta-carboline alkaloids previously reported as
      mild psychoactive compounds in animal studies and in vitro co-mutagens. These
      results support our previous conclusion that foods containing beta-carbolines are
      an important exogenous source of these alkaloids in humans.

PMID- 12227939
TI  - Ochratoxin A concentrations in food and feed from a region with Balkan Endemic
      Nephropathy.
AB  - Balkan Endemic Nephropathy (BEN), a chronic renal disease of unknown aetiology,
      is found in geographically close areas of Bulgaria, Romania, Serbia, Croatia,
      Bosnia and Herzegovina, Slovenia, and the former Yugoslav Republic of Macedonia.
      Ochratoxin A (OTA), a secondary metabolite of Aspergillus and Penicillium species
      and a natural contaminant of food and feed, is a putative cause of BEN. Some
      studies have found a geographic covariation between OTA content in food/feed and
      BEN manifestation; others have not. In May 2000, using a competitive direct ELISA
      assay for OTA (detection limit 1 microg kg(-1)), we investigated OTA
      contamination in 165 samples of home-produced food (beans, potatoes, corn, wheat,
      flour) and feed from households in villages from the BEN region (Vratza district)
      of north-western Bulgaria. Samples were collected from: (a) BEN villages (n = 8),
      and therein from BEN households (20), and BEN-free households (16) (within
      village controls, WVC households); and (b) BEN-free villages (7) and therein BEN
      free households (22) (between-village controls, BVC). BEN households consistently
      had a higher proportion of OTA-positive samples than WVC households, but similar
      (for some foods) or lower (for other foods) proportions to BVC households. The
      proportion of OTA-positive samples was also higher in BVC than in WVC households.
      Furthermore, BEN households had a similar proportion of OTA-positive samples to
      the pooled, WVC and BVC, group of households. OTA-exposure estimates, derived
      from our OTA-concentration findings and the reported average per capita monthly
      consumption of basic foods in rural Bulgaria, showed the highest OTA intake in
      BEN households (1.21 microg day(-1)), versus 1.03 microg day(-1) in BVC and 0.71
      microg day(-1) in WVC households. These OTA intakes are higher than those in the
      EU, and are close to the upper limits acceptable to several food-safety
      organizations. The results indicate that OTA may not alone cause BEN; only
      synergistically with other environmental toxicants and/or predisposing genotypes
      may do so.

PMID- 12227940
TI  - Moniliformin in barley inoculated with Fusarium avenaceum.
AB  - To assess production of the mycotoxin moniliformin, inoculation trials with four
      barley cultivars and local isolates of Fusarium avenaceum were performed at two
      different experimental farms in southern Manitoba, Canada, during 1997-99. In the
      1997 study, moniliformin was detected in 11 of 16 barley rows at levels between
      0.19 and 1.62 mg g(-1), and F. avenaceum infection ranged from 10 to 57% in rows
      where the toxin was detected. In the 1998 study, moniliformin was detected in
      only three of 16 barley rows, with levels between 0.06 and 0.43 micro g g(-1),
      and F. avenaceum infection between 16 and 39%. In the 1999 study, moniliformin
      was detected in 11 of 16 barley rows with levels between 0.09 and 0.42 micro g g(
      1), and F. avenaceum infection between 37 and 76%. In the 1997 trial,
      moniliformin was found in a single water-inoculated control row at 0.15 micro g
      g(-1). The data suggest that in years of high rainfall and F. avenaceum
      infection, moniliformin is likely to be found in Manitoba barley.

PMID- 12227941
TI  - Intake estimation of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs)
      and polychlorinated biphenyls (PCBs) in salmon: the inclusion of uncertainty.
AB  - Dioxins and dioxin-like PCBs are given toxic equivalency factors (TEFs) in order
      to calculate the combined toxic equivalence (TEQ) of these contaminants in a
      sample of food. This study calculates the probability of an average consumer
      exceeding the recommended tolerable daily intake of 1-4 pg WHO-TEQ kg(-1) bw day(
      1) as the amount of salmon in the diet is increased. Probabilistic risk analysis
      is used to account for the known uncertainties in this calculation. When the TEF
      uncertainty was excluded with no salmon consumption, the background dietary
      intake ranged from 1.36 to 1.78 pg TEQ kg(-1) bw day(-1). A weekly consumption of
      three standard salmon portions resulted in a 36% chance of exceeding the upper
      limit of the TDI. Inclusion of the TEF uncertainty increased the background
      dietary intake range from 2.1 to 4.4 pg TEQ kg(-1) bw day(-1), and the weekly
      consumption of one salmon portion resulted in a 79% chance of the average
      consumer exceeding the upper TDI. The most important factors contributing to the
      uncertainty in these results were, in order of magnitude, the TEF for PCB 126 and
      the sampling uncertainty (sample size) followed by the measurement uncertainty of
      PCB 126. We recommend that it is more important to increase sample size and
      produce more precise estimates in the TEF than to improve analytical accuracy.

PMID- 12227943
TI  - Survey of bisphenol A and bisphenol F in canned foods.
AB  - Bisphenol A (BPA) and bisphenol F (BPF) have been determined in a range of canned
      foods. Sixty-two different canned foods were purchased from retail outlets in the
      UK from January to November 2000 and the contents extracted and analysed by GC-MS
      for BPA and BPF isomers. The following canned products were analysed: fish in
      aqueous media, 10 samples; vegetables, 10; beverages, 11; soup, 10; desserts,
      five; fruit, two; infant formula, four; pasta, five; and meat products, five. BPF
      isomers were not detected in any of the canned foods with detection limits of
      0.005 mg kg(-1) for the 2,2' and 2,4' isomers and 0.01 mg kg(-1) for the 4,4'
      isomer. BPA was detected in 38 samples with a detection limit of 0.002 mg kg(-1).
      Of these, BPA was quantified in 37 canned foods at levels from 0.007 mg kg(-1),
      with one sample of meat containing a mean level of 0.38 mg kg(-1). All other
      samples contained <0.07 mg kg(-1) BPA.

PMID- 12227942
TI  - Polychlorinated biphenyls (PCBs) and their congener-specific accumulation in
      edible fish from the Gulf of Gdansk, Baltic Sea.
AB  - Concentrations and composition profiles of polychlorinated biphenyls (PCBs) were
      investigated in composite samples of 10 species of edible fish from the Gulf of
      Gdansk, in the southern part of the Baltic Sea, Poland, to understand the status
      of contamination and possible human exposure risk. Apart from the total PCBs,
      planar non-ortho (IUPAC nos 77, 126, 169) and mono-ortho (nos 105, 114, 118, 123,
      156, 157, 167, 189) chlorobiphenyls were also quantified and their dioxin-like
      toxicity assessed. The absolute total PCB concentrations in fish ranged from 43
      to 490 ng g(-1) wet wt (910-11000 ng g(-1) lipids), while of TCDD TEQs of planar
      members were from 0.15 to 3.1 pg g(-1) wet wt (8.1-81 pg g(-1) lipids). The penta
      and hexa-CBs usually comprised 70-80% of the total PCBs and were followed by
      hepta-, tetra- and tri-CBs, and for a specific site tri- and tetra-CBs comprised
      as much as 22%. Among the individual CB congeners, nos 118, 153 (+132) and 138
      (+160 +163 +164) were the most abundant, while no. 110 comprised between 6.8 and
      9.3% of the total PCBs in some species. Principal component analysis (PCA) was
      applied to examine the interdependences among CB congeners in the factor space.
      The PCA model and cluster analyses were further used to examine site- and species
      specific differences and similarities of PCB composition, and the results are
      discussed. An assessed daily intake rate of TCDD TEQ of planar PCBs with the
      fishmeal of the Gulf of Gdansk in the 1990s was between 78 and 96 pg per capita
      or between 1.3 and 1.6 pg kg(-1) body weight.

PMID- 12227944
TI  - From Renaissance art to contemporary electron microscopy: DeGroft's rediscovery
      of Titian's "lost" portrait of Federico II Gonzaga, Duke of Mantua, of 1539-40.
AB  - At the Ultrapath X meeting in Florence, the regular session opened with a
      presentation of Aaron DeGroft's engrossing story of investigating the
      authenticity of a portrait of Federico II Gonzaga, Duke of Mantua. In the early
      1900s, this work had been deemed to be an authentic production by Titian, a great
      artist of the Italian Renaissance. A respected art historian, however, discovered
      a conflict of dates that led to the conclusion that this work was not authentic.
      In a process sometimes analogous to the practice of surgical pathology, Dr.
      DeGroft pursued a review of the original materials that refutes this seeming
      contradiction of dates. Dr. DeGroft also undertook an extensive art historical
      examination and scientific analysis, including the use of electron microscopy, to
      persuasively conclude that this portrait is authentic. Further, his work provided
      a bridge from the conference setting in Florence, rich in Renaissance art, to the
      contemporary update on ultrastructural pathology provided by the conference.

PMID- 12227945
TI  - The value of electron microscopy in the diagnosis of IgA nephropathy.
AB  - Electron microscopy plays a fundamental role in the evaluation of renal diseases
      in general. IgA nephropathy represents a heterogeneous disease clinically and
      morphologically. There are a number of conditions that need to be considered in
      the differential diagnosis of IgA nephropathy. The renal pathologist must wisely
      integrate the light microscopic, immunofluorescence, and ultrastructural data
      when evaluating cases in which IgA nephropathy is a consideration. Electron
      microscopy can be crucial in providing information either to support a diagnosis
      of IgA nephropathy or to aid in the diagnosis of one of its mimics.

PMID- 12227947
TI  - Folliculo-stellate cells of the human pituitary: a type of adult stem cell?
AB  - Ultrastructural and immunocytochemical observations of pituitary folliculo
      stellate cells (FSC) in a large series of adenomatous and nontumorous human
      pituitaries led to the following conclusions: (1) The endocrine cells of both the
      nontumorous and the adenomatous pituitary are capable of transforming into FSC
      while changing from endocrine to nonendocrine phenotype. (2) As shown on
      consecutive sections in prolactin cell adenomas with FSC-rich areas including
      microcyst formation, S-100 protein and glial fibrillary acidic protein (GFAP)
      immunoreactivities are strongest in the smallest newly formed follicles. The 2
      immunoreactivities do not overlap. The epithelium of older microcysts is
      immunonegative, implying that expression of the 2 markers is restricted to the
      early phase of FSC formation. (3) Transformation of endocrine cells into FSC may
      signify retrodifferentiation into their Rathke's pouch derived precursors as
      suggested by occasional presence of ciliated and/or mucin producing cells in the
      lining of microcysts. (4) In lymphocytic hypophysitis a marked activation as well
      as increase of number and size of FSC are evident in areas of ongoing immune
      destruction supporting their immune role. (5) Considering the multifaceted nature
      of FSC, it is suggested that they represent a type of pluripotent adult stem
      cell.

PMID- 12227946
TI  - Ultrastructural and molecular heterogeneity in non-small cell lung carcinomas:
      study of 110 cases and review of the literature.
AB  - The authors reviewed a series of 110 surgical specimens of primary non-small cell
      lung carcinomas from the Department of Pathology at the Hospital Clinic,
      University of Barcelona Medical School, between 1987 and 1997. The sample
      included 25 squamous cell carcinomas, 60 adenocarcinomas, 14 large cell
      carcinomas, and 11 neuroendocrine tumors. Electron microscopic subcellular
      characteristics of the lung cancer cells were studied to define the squamous,
      adenoid, or neuroendocrine differentiation in each tumor. An immunohistochemical
      study for Cyclin D1 was performed in 96 cases. In 71 cases (65%) the author found
      a single ultrastructural differentiation, and in 30 cases (27%) ultrastructural
      differentiation was double: 25 adenosquamous and 5 adeno-neuroendocrine. In 3
      cases a triple adeno-squamous-neuroendocrine differentiation was found. There
      were no cases of squamous-neuroendocrine differentiation. In 6 cases no
      differentiation of any kind could be found. Cyclin D1 overexpression was found in
      58% of all tumors. The positive expression rates in squamous cell carcinoma and
      adenocarcinoma were 72% and 62%, respectively. In purely adenoid-differentiated
      tumors there was a strong association between high Cyclin D1 overexpression and
      differentiation (p=.006). In bronchioloalveolar carcinoma the positivity rate was
      70%; all were heavy expressers, compared with 25% of heavy expressers in
      adenocarcinomas as a whole (p<.005). In purely squamous tumors differentiated
      ultrastructurally no relationship was found between high Cyclin D1 expression and
      degree of differentiation (p=.08). Lung cancers are morphologically and
      molecularly heterogeneous, and certain molecular alterations are related to
      specific subcellular characteristics.

PMID- 12227948
TI  - Peculiar cytoplasmic inclusions in oncocytic adrenal cortical tumors: an electron
      microscopic observation.
AB  - Two cases of an oncocytic adrenal cortical tumor that contained peculiar
      cytoplasmic crystalline inclusions in the tumor cells are presented. The patients
      were 49- and 72-year-old females without clinical and biochemical evidence of
      adrenal cortical or medullary dysfunction. The adrenal tumors weighed 80 and 200
      g each. These crystalline inclusions were present in groups of longitudinal
      profiles or clusters of crossly cut aggregates. They appeared in clusters of
      membrane-bound columns. On longitudinal sections, they appeared as rigid rods of
      homogenous density measuring 36 nm in width, but when they were cut transversely
      their paracrystalline nature became apparent. They were composed of closely
      packed microtubules in rectangular blocks. The microtubules measured 12.5 nm with
      a hollow center measuring 4.2 nm. The inclusions were within the membrane-bound
      cisterna of rough-surfaced endoplasmic reticulum. The significance of these
      inclusions is not clearly understood; however, they have been seen only in
      adrenal cortical tumors and their presence may be helpful in the differential
      diagnosis of adrenal oncocytic tumors. One patient presented with a tumor in
      which gross and microscopic appearance was compatible with a pheochromocytoma.
      This case exhibited an oncocytic appearance and pronounced cellular pleomorphism.
      Ultrastructural studies were necessary to recognize the tumor cells as cortical
      cells. The tumor cells contained abundant mitochondria with tubular cristae,
      paranuclear parallel stacks of granular endoplasmic reticulum, and relatively
      prominent smooth endoplasmic reticulum. These features are typical of
      adrenocortical cells. In addition, frequent tumor cells contained the peculiar
      cytoplasmic inclusions herein described.

PMID- 12227949
TI  - Correlation between morphology, immunohistochemistry and molecular pathology in
      hereditary and sporadic breast cancer cases.
AB  - Breast cancer still represents a serious health problem and is currently the most
      frequent malignancy in the female population in developed countries. In Cyprus,
      there are 300 new cases annually. In the present study, histology, electron
      microscopy, immunohistochemistry, and Western blot analysis were used to
      investigate 100 cases of invasive breast carcinoma. In addition, mutation
      analysis for the BRCA1 gene was carried out in patient DNA from 26 families with
      multiple cases of breast/ovarian cancers. Of note are the results of molecular
      biology which show that there are no germline truncating mutations in the BRCA1
      gene in these 26 Cypriot breast cancer families. Furthermore, Western blot
      analysis revealed the presence of multiple BRCA1 bands in homogenates of tumor
      and normal tissues, and immunoelectron microscopy showed the presence of nuclear
      staining for BRCA1 antibodies.

PMID- 12227950
TI  - Ultrastructure of HIV/AIDS.
AB  - Transmission electron microscopy has played a key role in our understanding of
      the human immunodeficiency virus and the opportunistic infections that accompany
      HIV disease. This paper describes features of HIV production; HHV-8, the virus
      that is associated with Kaposi sarcoma; Trachipleistophora anthropophthera, a new
      disseminating microsporidian; and bacterial enteritis, which causes diarrhea in
      patients with AIDS.

PMID- 12227951
TI  - Mechanical aortic injury in apoE-deficient mice as a model for development of
      atherosclerosis: demonstration of leukocyte rolling early after injury.
AB  - A mouse model of aortic endothelium regeneration following mechanical injury was
      studied in wild-type and apoE-deficient (apoE0) animals. The injury induced a
      topologically nonuniform and complex reparative response. Compared to wild-type
      animals, apoE0 mice had unaltered ability to regenerate endothelium. Despite the
      pro-coagulative state of the apoE0 mice, no arterial thromboses were detected.
      Only deeper arterial injury with damage to the internal elastic membrane was
      associated with the development of atherosclerotic lesions in apoE0 mice. During
      the limited observation period of 7 days, superficial arterial injury in apoE0
      mice was inconsequential. In addition, for the first time in vivo, rolling of
      polymorphonuclear leukocytes over the damaged endothelium was documented.

PMID- 12227952
TI  - Sclerosing hemangioma of the lung in a young woman with cutaneous melanoma: the
      role of electron microscopy in preventing an erroneous diagnosis of metastasis.
AB  - A young woman with a melanoma of the left forearm was found to have a right lung
      mass. This was initially interpreted as metastatic melanoma on the basis of
      clinical, radiographic, and light microscopic features, together with positive
      staining of tumor cells with antibody HMB-45. Electron microscopic examination
      performed for confirmation of the diagnosis revealed no evidence of melanocytic
      differentiation. Instead, there were features suggestive of the alternative
      diagnosis of sclerosing hemangioma (SH). This diagnosis was confirmed with
      additional immunocytochemical stains. To the authors' knowledge this is the first
      report of HMB-45 positivity in SH. This case illustrates a potentially disastrous
      diagnostic pitfall in interpreting lung tumors in patients with melanoma, and the
      vital role of electron microscopy in resolving conflicting and/or misleading
      immunocytochemical results.

PMID- 12227953
TI  - Detection of polychlorinated biphenyls and dioxins in Belgian cattle and
      estimation of the maximal potential exposure in humans through diets of bovine
      origin.
AB  - The methodology used to detect a polychlorinated biphenyl (PCB)/dioxin
      contamination in a Belgian cattle population that was not exposed to the
      PCB/dioxin incident in 1999 is presented. This population is directly or
      indirectly destined for human consumption. The methodology consisted in the
      systematic sampling of all calf-fattening stations and groups of cattle destined
      for export, and in the random sampling of slaughter cattle. This approach is
      compared to the method described in directive 96/23/CE from the European Council.
      When PCB concentrations exceeded the tolerance level of 0.2 micro g/g body fat
      (seven congeners with numbers 28, 52, 101, 118, 138, 153, and 180), dioxins
      (seventeen 2,3,7,8-substituted congeners of PCDD and PCDF) were also determined.
      The prevalence of Belgian slaughter cattle with PCB concentrations above this
      cutoff was 0.3% (95% confidence interval: 0.01-1.50%). Results indicate that the
      incidence of contamination was minimal, with environmental origin and common in
      all industrial countries. The maximal potential exposure of an adult human
      consumer to dioxins through diet of bovine origin is estimated in two worst-case
      scenarios. The first one corresponds to the consumption of contaminated food
      products by a small number of consumers during a long period (local consumption)
      and the second simulates the consumption of contaminated products by a large
      number of consumers during a short period (supermarket purchase). The theoretical
      maximum daily intake of dioxins in adults was respectively 374 and 123 pg TEQ/d.
      The estimated maximum increase of dioxin body burden corresponds to 7 pg TEQ/g
      fat in the local consumption scheme and 0.07 pg TEQ/g fat in the supermarket
      consumption scheme.

PMID- 12227954
TI  - Systemic uptake and cutaneous disposition of pentachlorophenol in a sequential
      exposure scenario: effects of skin preexposure to benzo[a]pyrene.
AB  - Characterizing interactions caused by sequential skin exposures to various
      environmental toxicants can be critical for a meaningful risk assessment. To
      assess sequential chemical exposure effect on chemical cutaneous disposition and
      systemic uptake of a toxicant, [(14)C]pentachlorophenol (PCP) was topically
      administered in three porcine skin models (in vivo, ex vivo, and in vitro) at 40
      micro g/cm(2) with or without skin preexposure to benzo[a]pyrene (BaP), a known
      human carcinogen and cutaneous cytochrome P-450 (CYP450) inducer. In the mass
      balance studies, BaP skin preexposure was found to enhance (14)C absorption in
      all three models with detectable in vivo effect during the first several days.
      Total 8-h absorption was tripled by skin preexposure to BaP in the ex vivo (1.1
      to 3.2%) and in vitro (0.20 to 0.66%) systems. As seen in the extended in vivo
      studies, total absorption was 50-57% regardless of exposure conditions,
      suggesting the prolonged observation period may conceal existing impact of
      potentially modified disposition processes, such as cutaneous metabolism, on
      systemic absorption. Skin preexposure to the skin CYP450 inducer BaP largely
      changed label penetration depth and distribution pattern in cutaneous tissues and
      decreased (14)C concentration in skin and fat. Additionally, BaP preexposure
      altered (14)C systemic tissue disposition, suggesting that altered cutaneous PCP
      disposition may eventually change the toxicity profile (cutaneous vs. systemic
      risk). The preliminary tissue distribution and systemic absorption data suggested
      that skin preexposure to BaP may considerably modify cutaneous biotransformation
      rate and thus deserves further investigation. The dermal model-dependent impacts
      of expected skin biotransformation manipulation by preexposure to chemicals such
      as BaP on cutaneous disposition and systemic uptake of environmental toxicants
      such as PCP need to be considered in risk assessment.

PMID- 12227955
TI  - Altered gene expression profiles of rat lung in response to an emission
      particulate and its metal constituents.
AB  - Comprehensive and systematic approaches are needed to understand the molecular
      basis for the health effects of particulate matter (PM) reported in
      epidemiological studies. Due to the complex nature of the pollutant and the
      altered physiological conditions of predisposed populations, it has been
      difficult to establish a direct cause and effect relationship. A high-throughput
      technology such as gene expression profiling may be useful in identifying
      molecular networks implicated in the health effects of PM and its causative
      constituents. Differential gene expression profiles derived for rat lungs exposed
      to PM and its constituent metals using a custom rat cardiopulmonary cDNA array
      are presented here. This array consists of 84 cardiopulmonary-related genes
      representing various biological functions such as lung injury/inflammation,
      repair/remodeling, structural and matrix alterations, and vascular contractility,
      as well as six expressed sequence tags (ESTs). The cDNA array was hybridized with
      (32)P-labeled cDNA generated from rat lung RNA. Total lung RNA was isolated from
      male Sprague-Dawley rats at 3 and 24 h following intratracheal instillation of
      either saline, residual oil fly ash (ROFA; 3.3 mg/kg), or its most toxic metallic
      constituents, nickel (NiSO(4); 3.3 mmol/kg) and vanadium (VSO(4); 5.7 mmol/kg).
      Metal concentrations reflected the levels present in one ROFA instillate.
      Densitometric scans of the array blots indicated ROFA- and metal-specific
      increased expression (1.5 to 3-fold) of stress response, inflammatory, and repair
      related genes, and also genes involved in vascular contractility and thrombogenic
      activity. Expression of multiple cytokines in ROFA exposed rat lung compared to
      Ni and V suggest the role and importance of understanding constituent
      interactions in PM toxicity. Expression profiling using genomic approaches will
      aid in our understanding of toxicant-specific altered molecular pathways in lung
      injury and pathogenesis.

PMID- 12227956
TI  - Airway hyperresponsiveness caused by aerosol exposure to residual oil fly ash
      leachate in mice.
AB  - Particulate air pollution is associated with exacerbation of asthma and other
      respiratory disorders. This study sought to further characterize the pulmonary
      effects of residual oil fly ash (ROFA), an experimentally useful surrogate for
      combustion-derived particulates in ambient air. Mice were exposed to aerosols of
      the soluble leachate of residual oil fly ash (ROFA-s). Physiologic testing of
      airway function (non invasive plethysmography) showed increased Penh, an index of
      airway hyperresponsiveness (AHR), in a time- and dose-dependent manner after
      exposure to ROFA-s. BAL analysis showed a minor influx of neutrophils, which was
      maximal at 12 h after exposure and essentially resolved by the time point of
      maximal AHR (48 h after exposure). The AHR caused by ROFA-s was reproduced by a
      mixture of its major metal components (Ni, V, Zn, Co, Mn, Cu) but not by any
      individual metal alone. Systemic pretreatment of mice with the antioxidant
      dimethylthiourea abrogated ROFA-s-mediated AHR. Analysis of mice of varying ages
      showed that ROFA-s had no marked effect on airway responsiveness of 2-wk-old
      mice, in contrast to the AHR seen in 3- and 8-wk old mice. ROFA-s-mediated AHR
      was unchanged in neurokinin 1 receptor knockout mice and in mice treated with an
      neurokinin antagonist, arguing against a role for this mediator in ROFA-s
      mediated effects. Data indicate that ROFA-s mediates AHR in mice through
      antioxidant-sensitive mechanisms that require multiple metal constituents.
      Maturational differences in susceptibility to ROFA-induced AHR may be useful for
      further studies of mechanisms of particle effects.

PMID- 12227957
TI  - Temperature-dependent quinone cytotoxicity in platelets involves arylation.
AB  - Menadione (MEN), a representative quinone compound, produces cytotoxicity in many
      cells by arylation with protein thiols and oxidative stress due to redox cycling.
      Previously it was demonstrated that protein arylation appears to be a primary
      mechanism for MEN-induced toxicity in platelets. To test the hypothesis that
      temperature conditions may be important in MEN-induced cytotoxicity in noncancer
      cells, platelets were incubated with menadione at 25, 37, or 42 degrees C. As
      temperature was increased, MEN significantly enhanced lactate dehydrogenase (LDH)
      leakage. MEN-induced depletion of protein thiol levels also increased as
      temperature was elevated. To investigate the mechanism of temperature-dependent
      MEN cytotoxicity, MEN-induced platelet toxicity was compared to two other quinone
      substances. Benzoquinone (BQ), which acts via arylation, produced cytotoxic
      effects similar to those of MEN. Dimethoxy-1,4-naphthoquinone (DMNQ), which
      exerts toxicity via oxidative radical generation, failed to produce cytotoxicity
      at all three temperatures. While MEN and DMNQ enhanced O(2) consumption in a
      temperature-dependent manner, BQ did not affect this parameter. MEN, which
      possesses an electrophilic 3-position, was found to react with thiols to form a
      thioether linkage, a direct indicator of arylation. In the case of MEN uptake
      kinetics, the amount of cellular uptake was not different at various
      temperatures, but concentration of MEN in extracellular medium decreased
      temperature dependently. This might be due to increased arylation capacity
      binding to cellular proteins as temperature rises. These data suggest that MEN
      induced platelet cytotoxicity involves arylation that is temperature related.

PMID- 12227958
TI  - Reducing social inequalities in health: evidence, policy, and practice.
AB  - Many policy documents have expressed concerns and intentions for action regarding
      inequity in health. However, the evidence on how to establish effective and
      acceptable interventions is rather scarce. During an international conference in
      Copenhagen September 2000 organised by the City of Copenhagen and the Danish
      Ministry of Health the present evidence was presented and possible policy
      measures and intervention strategies were discussed. This special issue of the
      Scandinavian Journal of Public Health includes selected papers and presentations
      from the conference. Four main arenas for interventions were outlined: the
      workplace; healthcare services; local communities and families; and urban
      development. Public health will have to move out of the present reactive position
      to say what its contribution is to shaping the society of the future with less
      inequity in health. The papers show that a number of theories, concepts, and
      tools are available, but also that we still have much to learn and do. At the end
      of the conference a final declaration on reducing social inequalities was
      endorsed outlining important general themes that have universal relevance for
      action.

PMID- 12227959
TI  - National policies for reducing social inequalities in health in Europe.
AB  - Gaps in health between poor and rich countries, and between social groups within
      countries, are unacceptably large and may be widening. WHO has made the fight
      against inequities in health a priority in the European region, as part of the
      policy framework for health for all in the twenty-first century (HEALTH21), aimed
      at allowing all people to participate in social and economic life. It proposes a
      number of concrete steps, in order to promote access to health and reduce
      inequalities in health status. Equity should be everybody's concern, because
      inequities in health are everybody's loss. They harm many people, operate on a
      socioeconomic gradient, and put a strain on economic development and social
      cohesion. Equity is not something that is achieved once for all. A three-pronged
      approach to action includes: provision to all people of a "decent minimum" of
      assets and resources for creating and maintaining health and living; targeted
      additional support for disadvantaged groups in ways that respect their dignity
      and human rights; and appropriate policies, actions, and investments to secure
      opportunities and support at all levels of society. Genuine progress can be
      achieved by: * securing a champion and making action understood and attractive; *
      identifying and acting on needs; * working in partnership and at different levels
      - community, subnational, national, and international; * mobilizing investment
      for health; * building in accountability for health; * agreeing on policy
      choices, and reallocating resources and responsibilities accordingly; * learning
      and developing knowledge, and looking around and ahead.

PMID- 12227961
TI  - Generating evidence on interventions to reduce inequalities in health: the Dutch
      case.
AB  - The aim of this paper is to reflect on the type of evidence that is required to
      design policy measures and interventions to reduce inequalities in health. This
      issue will be discussed in the context of the Dutch national research programmes
      on inequalities in health. The first type of evidence relates to the background
      of socioeconomic inequalities in health. From a very simple conceptual scheme,
      four policy options can be derived: (1) reducing inequalities in socioeconomic
      goods; (2) changing the distribution of specific risk factors across
      socioeconomic groups; (3) diminishing the effect of health on socioeconomic
      status; (4) offering extra healthcare for people in lower socioeconomic groups.
      Whereas the evidence on the background of socioeconomic inequalities in health
      has increased enormously, there is clearly a lack of evidence on the
      effectiveness of interventions to tackle inequalities in health, which is the
      second type of evidence that is required. The Dutch five-year programme,
      including 12 (quasi) experimental studies on specific interventions in different
      policy fields, showed that this second type of evidence is more difficult to
      collect, partly because of the methodological complexity of these studies. The
      third type of evidence relates to the political feasibility of policy measures.
      It is not enough to know that a specific determinant of socioeconomic
      inequalities in health might be effectively addressed by a specific intervention.
      The political will to implement that intervention is obviously a necessary
      prerequisite for actually reducing inequalities in health. Within the Dutch
      research programme, the political feasibility of policy measures was explored
      during a number of conferences, for several policy fields. The lack of evidence
      on, in particular, the effectiveness of interventions to reduce inequalities in
      health is clearly an obstacle to tackling inequalities in health. On the other
      hand, it should be ensured that the lack of evidence is not used as an excuse for
      not taking policy measures at all.

PMID- 12227960
TI  - Tackling social inequality through the development of health policy in Lithuania.
AB  - AIMS: The major aim of this study was to assess existing inequalities in health
      of Lithuanian population and to present the process of health policy development
      as a major tool for reducing inequalities. The objectives were: to present life
      expectancy and mortality trend analysis in comparison with other European
      countries; to demonstrate risk profile of Lithuanian population to major
      noncommunicable diseases related to social inequalities and inequities in health;
      and to present the process of National health policy development as potential for
      effective reduction of inequalities in health of Lithuanian population. METHODS:
      Information about demographic, general health situation and inequalities in
      health was obtained from Lithuanian Department of Statistics, National Health
      Information Centre and research studies performed at Kaunas University of
      Medicine. RESULTS: Considerable demographic, social and territorial inequalities
      in health were disclosed in Lithuania. Large proportion of them might be related
      to social inequalities in the society. Substantial improvements in health status
      of Lithuanian population could be expected if due attention was paid to social
      determinants of health. CONCLUSION: Implementation of balanced national health
      policy involving all sectors of the society is the solution.

PMID- 12227963
TI  - Inequalities in urban areas: innovative approaches to complex issues.
AB  - Urbanization, a characteristic of the twentieth century, is a profound
      transformation of human settlement processes and their outcomes, which has not
      been well understood in terms of both positive and negative impacts. This paper
      argues that the interrelations between urban planning, health, social, and
      environmental policies have been poorly articulated until now. Although sectoral
      approaches have often applied remedial and corrective measures to overcome
      unsatisfactory conditions in urban areas, today we know that infectious diseases
      stemming from insanitary conditions are not the leading cause of morbidity and
      mortality in Europe. Nonetheless diverse forms of ill health remain associated
      with place of work and residence. Therefore, in order to deal with the complexity
      and diversity of urban areas there is an urgent need to move from conventional,
      sectoral approaches based on biomedical models of health to coordinated action
      stemming from an ecological interpretation of health including its social
      determinants. This kind of approach is presented in order to promote health and
      social development at the local level.

PMID- 12227962
TI  - Sickness leave, administrative category and gender: results from the "Casa Gran"
      project.
AB  - OBJECTIVE: The aim of this study was to analyse the variations of sickness leave
      rates among the Barcelona city council civil servants by administrative category
      and gender. METHODS: The study was a retrospective cohort including all people
      who worked for more than six months for the City Council of Barcelona from 1
      January 1984 to 31 December 1993. The cohort was composed of 11,647 men and 9,001
      women who contribute to a total of 134,928.7 person/years of follow-up. The study
      population was classified into administrative categories. Sickness leaves were
      classified into short episodes (less than 11 days) and long episodes (more than
      10 days). Age-specific rates of long and short episodes of sickness leave were
      computed in a gender-specific analysis. RESULTS: Among men, rate ratios of long
      spells increased constantly from the middle technician category to the unskilled
      worker category for the three oldest age groups. This social pattern was not as
      clear for younger workers. Among women, rate ratios of long spells showed far
      fewer differences than among men. The social gradient was evident for the three
      youngest age groups, with the exception of the unskilled workers. The oldest age
      group showed similar differences between all categories. Short spells followed a
      different pattern for men and women. CONCLUSIONS: Women had generally higher
      rates than men did, and manual categories had higher rates than non-manual ones,
      which was more evident for men and long episodes. The relationship between
      incidence rates and gender could be due to the different contents of the jobs
      performed by men and women, the influence of gender-based work segregation, and
      the unequal share of the reproductive workload between men and women, information
      which was not available for this study.

PMID- 12227964
TI  - Socioeconomic status and psychosocial work environment: results from a Danish
      national study.
AB  - OBJECTIVE: The aim of this study was to analyse the associations between
      socioeconomic status (SES ) and a number of psychosocial work environment factors
      with a potential impact on inequality in health. METHODS: A representative sample
      of 1,684 adult Danish employees filled in a standardized questionnaire or were
      interviewed by telephone. The response rate was 62%. The population was divided
      into four levels of SES (I to IV ). The psychosocial work environment was
      described with 19 scales. RESULTS: Quantitative, cognitive, and emotional job
      demands and a number of dimensions related to active and developmental work
      showed higher levels among high SES individuals. Job insecurity was highest among
      women with low SES. Dimensions describing interpersonal relations, social
      support, and leadership showed no clear associations with SES. CONCLUSIONS:
      Prevention aiming at improving health and reducing inequality in health should
      focus on the dimensions of active and developmental work: influence at work,
      possibilities for development, degrees of freedom, and meaning of work.
      Furthermore, job insecurity should be reduced.

PMID- 12227965
TI  - Reducing social inequalities in health: work-related strategies.
AB  - Despite reduced health risks in terms of physical and chemical hazards current
      trends in occupational life continue to contribute to ill health and disease
      among economically active people. Stress at work plays a crucial role in this
      respect, as evidenced by recent scientific progress. This paper discusses two
      leading theoretical models of work-related stress, the demand-control model and
      the model of effort-reward imbalance, and it summarizes available evidence on
      adverse health effects. As work stress in terms of these models is more prevalent
      among lower socioeconomic status groups, these conditions contribute to the
      explanation of socially graded risks of morbidity and mortality in midlife.
      Implications of this new knowledge for the design and implementation of worksite
      health-promotion measures are elaborated. In conclusion, it is argued that
      workplace strategies deserve high priority on any agenda that aims at reducing
      social inequalities in health.

PMID- 12227966
TI  - What can health services contribute to the reduction of inequalities in health?
AB  - Policies to reduce inequalities in health are needed in many different settings,
      one of which is the healthcare setting. This paper, drawing on the conclusions of
      the Copenhagen conference, explores the contribution that such policies can make
      within the healthcare system. In doing so it examines four themes. It begins by
      exploring the contribution that healthcare makes to health. It challenges the
      widely held view that this contribution is small, arguing that there have been
      major advances in the effectiveness of medical care and the use of evidence-based
      healthcare, so that interventions of proven effectiveness are increasingly
      delivered to those who will benefit. Unfortunately, there is growing evidence
      that the benefits of modern healthcare do not benefit all groups equally. Thus,
      there is an unfinished agenda in many countries to enhance the equitable
      distribution of access to effective healthcare. Second, it explores the dynamic
      relationship between illness and poverty and, specifically, the impoverishing
      nature of illness in the absence of effective mechanisms to ensure solidarity and
      to provide social safety nets. It identifies how all elements within a healthcare
      system have a part to play. Those responsible for healthcare financing should
      ensure that funds are obtained in an equitable manner. Those who provide
      healthcare can do much to promote access for the disadvantaged and to use their
      facilities to promote health as well as cure disease. Third, it considers the
      specific needs of disadvantaged populations, and especially those whose needs are
      least visible, such as illegal migrants. It concludes by reviewing the need for
      better information to document the scale of inequalities, to evaluate
      interventions designed to reduce them, and to disseminate evidence of good
      practice.

PMID- 12227967
TI  - Urban development and health inequalities.
AB  - Urban development has historically been seen as both a cause and solution for
      social inequalities in health. However, environmental and individual gradients
      within urban areas occur everywhere, and are resistant to change. Environments
      are influenced by the degree and type of industrialization, quality of housing,
      accessibility to green space and - of increasing concern - transport. Individual
      behaviour, however, also contributes to social differences, both through
      migration and by the effects on individuals of cultural experiences through the
      life-course. Reduction on inequalities may be possible through larger social
      action, for example urban regeneration. There remains an important role for
      public health in addressing determinants of health at the population level.

PMID- 12227968
TI  - The Rotterdam Local Health Information System 1987-2000: from Rebus and the
      health barometer to the health monitor.
AB  - In this article the development of the Rotterdam Local Health Information System
      is sketched. Started as an offspring of the Healthy Cities Project of the WHO,
      the focus was very much on neighbourhoods. The data were presented by a software
      program, REBUS Vision. It was relatively new to gather information at the
      neighbourhood level, so not much consideration was given to the relative
      importance of data for research questions. This led to the need to condense the
      vast amount of data into some summary figure, the health barometer, which chose
      the 27 most important available neighbourhood indicators and divided these data
      into six groups leading to six scores in which a neighbourhood could be compared
      with the city mean, other neighbourhoods, or itself in time. Although REBUS
      Vision and the health barometer were reasonably successful, a frequently
      occurring criticism was that there was too much emphasis on the signalling of
      public health problems. This has led to the development of a health monitor that
      not only signals public health problems but also tries to identify determinants
      and to offer solutions on a health policy and promotion level.

PMID- 12227969
TI  - Empowerment to reduce health disparities.
AB  - This article articulates the theoretical construct of empowerment and its
      importance for health-enhancing strategies to reduce health disparities.
      Powerlessness is explored as a risk factor in the context of social determinants,
      such as poverty, discrimination, workplace hazards, and income inequities.
      Empowerment is presented and compared with social capital and community capacity
      as strategies to strengthen social protective factors. A case study of a youth
      empowerment and policy project in New Mexico illustrates the usefulness of
      empowerment strategies in both targeting social determinants, such as public
      policies which are detrimental to youth, and improving community capacities of
      youth to be advocates for social change. Challenges for future practice and
      research are articulated.

PMID- 12227970
TI  - The Copenhagen declaration on reducing social inequalities in health.
AB  - The International Conference on Reducing Social Inequalities in Health was held
      in Copenhagen from 27 to 29 September 2000. Policy makers, researchers and
      decision makers at the community level took part in the conference. The
      conference brought into focus the problem of social inequalities in health and
      called attention to ways of reducing them by promoting equity in health. Building
      on existing international agreements that access to healthcare is a fundamental
      human right we urge all communities to accept their responsibility for reducing
      social inequalities in health when documented and effective methods are available
      for doing so. These methods should be acceptable, participative and improve
      health for everyone. Healthcare, disease prevention and health promotion should
      particularly benefit disadvantaged people. The conference endorsed the
      Declaration on 29 September 2000.

PMID- 12227972
TI  - Bridging the gaps: can we afford not to invest in global health?

PMID- 12227973
TI  - Do common symptoms in women predict long spells of sickness absence? A
      prospective community-based study on Swedish women 40 to 50 years of age.
AB  - AIMS: To investigate whether a high level of commonly experienced physical and
      mental symptoms could predict long spells of sickness absence in Swedish women
      and, further, to investigate the causal pattern of socioeconomic and psychosocial
      factors in relation to long spells of sickness absence. METHODS: A questionnaire
      containing items on socioeconomic and psychosocial variables was sent to a random
      population of women, 40 to 50 years of age, living in a rural Swedish community.
      The response rate was 81.7% (397 women). Data on long spells of sickness absence
      (>14 days) for the year following the baseline survey were obtained from the
      social insurance office. Odds ratios (OR) were used to estimate bivariate
      associations. Multiple logistic regression analysis was used to test for
      confounding and effect modification. RESULTS: Women suffering from a high level
      of common symptoms were at risk of subsequent long spells of sickness absence, OR
      = 3.39 (1.86-6.17). High demands at work and an active job position (i.e. the
      combination of high demands and a high degree of job control) were both
      associated with long spells of sickness absence, OR = 2.16 (1.12-4.17) and OR =
      1.92 (1.01-3.67). The combined exposure (high level of common symptoms and an
      active job position) increased the odds for long spells of sickness absence (OR =
      9.13; 3.39-24.58) with synergy noted. CONCLUSIONS: The finding that women with
      common symptoms are at risk of future sickness absence is of particular
      importance in a primary health care setting. The finding that women in active job
      positions had a higher risk of sickness absence might be an effect of modern
      working conditions for women.

PMID- 12227974
TI  - Social network, social support and the rate of decline of CD4 lymphocytes in
      asymptomatic HIV-positive homosexual men.
AB  - AIMS: To test a stress-disease hypothesis by investigating the influence of
      social network and social support factors on the course over time of the CD4
      lymphocytes in an HIV-positive population of gay men. METHODS: The study is a
      prospective cohort study of a representative population of HIV-positive gay men,
      undertaken at the Department of Infectious Diseases, Malmo University Hospital.
      This is the only clinic providing care for HIV-positive individuals in the city
      of Malmo in southern Sweden (population 248,000). A total of 115 HIV-positive
      homosexual men, who had not received an AIDS diagnosis, were invited to take part
      in the study. Seventy-five men (65%) accepted to be interviewed and 64 men (56%)
      fulfilled the inclusion criteria for the statistical analysis. RESULTS: In a
      multivariate analysis adjustments were made for age, level of the first CD4 count
      and time since first contact with the clinic. Men with high family contact
      frequency had a longer half-life (20.3 years) of the CD4 lymphocyte count than
      men with a low family contact frequency (7.4 years) (p = 0.03). Men with high
      social participation also had a longer half-life of CD4 lymphocyte count (14.7
      years), compared with men with low social participation (6.3 years, p = 0.10).
      CONCLUSIONS: The findings of this study imply the importance of social support
      and social network factors as modifiers of the rate of decline of the CD4
      lymphocyte level, which is an important prognostic marker of survival in HIV
      positive homosexual men.

PMID- 12227975
TI  - An explorative, population-based study of female disability pensioners: the role
      of childhood conditions and alcohol abuse/dependence.
AB  - AIMS: This study investigates the association in women between conditions during
      childhood and adolescence and alcohol dependence or abuse in adulthood on the one
      hand, and disability pensions and long-term sickness absence on the other.
      METHODS: A stratified population-based sample of women in Goteborg was
      interviewed. For analyses in this study the following variables were selected
      from the interview protocol: childhood and adolescence, education, employment,
      social class, self-rated physical health and alcohol dependence or abuse (ADA),
      with diagnoses assessed according to DSM-III-R. Information on disability pension
      and sickness absence was obtained from the local Social Insurance Office.
      RESULTS: Unfavourable conditions during childhood and adolescence and school
      difficulties as well as early deviant behaviours predicted disability pension and
      long-term sickness absence in adulthood. For most risk factors ADA could explain
      only a minor part of the odds ratios found in crude and age-adjusted analyses.
      CONCLUSION: It is concluded that conditions early in life are predictors in women
      of disability pension and long-term incapacity to work. There are similarities in
      the pattern of early risk factors for later alcohol dependence or abuse and for
      disability pension/long-term sickness absence.

PMID- 12227976
TI  - Health promotive action and preventive action model (HPA model) for the
      classification of health care services in public health nursing.
AB  - BACKGROUND: There is a need for an expanded approach to develop knowledge of
      public health nursing as a sphere of public health. The aim of this paper was to
      construct a theoretical model for healthcare services in the area of public
      health nursing based on the analysis and classification of healthcare services
      used in public health nursing practice. METHODS: Patient records were examined
      using a qualitative research approach. The categorization and classification of
      the actions followed certain criteria. Three methods were used for verifying and
      modifying the concept. RESULTS: Of the identified categories 34 dealt with
      healthcare services, three with administrative services, and five with
      coordination. The six recognized domains of the healthcare services are health
      promotive services, health protective services, diagnostic services, therapeutic
      services, rehabilitation services, and terminal healthcare services. Using the
      public health approach, the Health promotive action and preventive action model
      (HPA model) was constructed in order to visualize where in the course of the
      process of health-ill health and developmental stages the public health nurses
      provide healthcare services. Health promotion and the levels of prevention are
      described on the operational and conceptual levels in this paper. CONCLUSIONS:
      The result is expected to have an important effect on how public health nurses
      conceptualize their field of knowledge. The classification reflects current
      public health policy by focusing on health promotion and illness prevention. The
      developed HPA model will support health service research.

PMID- 12227977
TI  - Organizational fairness and psychological distress in hospital physicians.
AB  - AIMS: Prior research has reported high levels of stress for physicians, but
      determinants of this stress are poorly understood. We explored whether problems
      in decision-making procedures and treatment of employees, as expressed in the
      theory of organizational fairness, may contribute to psychological distress in
      hospital physicians. METHODS: Structural equation modelling (LISREL) was based on
      survey responses from 251 male and 196 female physicians working in 11 public
      hospitals in Finland. RESULTS: Low organizational fairness increased the risk of
      psychological distress in male physicians but not in female physicians. In the
      former group, the association between organizational fairness and psychological
      distress was partially mediated by decreased job control and increased workload.
      CONCLUSIONS: These findings suggest that broadening the view from the traditional
      psychosocial work characteristics to justice in management may assist in efforts
      to promote physicians' health and well-being.

PMID- 12227979
TI  - Subjective health complaints in adolescence: dimensional structure and variation
      across gender and age.
AB  - AIMS: The aim of this study is to investigate dimensional structures in
      subjective health complaints in adolescents and to examine the variation in
      levels and dimensionality across gender and age groups. METHODS: Data from two
      studies were used: (1) a study based on a convenience sample, consisting of 1427
      Norwegian students (11- to 15-year-olds) from schools participating in the
      European Network of Health Promoting Schools; (2) a nationwide survey amongst
      7,059 Norwegian students (aged 11, 13, 15, and 16) from the Health Behaviour in
      School-aged Children (HBSC) study. Subjective health complaints were measured by
      revised versions of the HBSC symptoms checklist (HBSC-SCL). RESULTS: In study 1
      confirmatory factor analysis revealed that a model of two highly correlated
      factors, which can be labelled somatic and psychological, fitted the data
      reasonably well (CFI = 0.91). This two-factor model was applied in study 2 and
      latent means were tested across sub-samples defined by gender and age. The
      results indicate that girls show higher mean levels compared with boys on both
      factors. There is also an indication of an increase in these factors with age
      amongst girls, while amongst boys there is less, if any, difference across age
      groups. The correlation between the somatic and psychological factors was
      virtually constant across age groups and gender. CONCLUSIONS: The identification
      of a somatic and a psychological factor indicates the existence of two different
      dimensions that may have different aetiologies. The gender difference in latent
      means across age groups may suggest a different developmental pattern amongst
      girls and boys.

PMID- 12227978
TI  - Mortality in relation to early retirement in Denmark: a population-based study.
AB  - AIMS: The aim of this study was to examine whether early retirement is gained by
      persons with poor health or whether retirement leads to negative changes in
      health. Mortality for persons in Denmark using one of two publicly financed
      retirement schemes was investigated. Disability benefit (fortidspension) was
      granted for health reasons mainly, while early retirement benefit (efterlon) was
      earned through long-term membership of an unemployment benefit scheme. METHODS:
      Data from Danish population-based registers were used for each year in the period
      1986-96. The study setting was the population of Denmark, born between 1926 and
      1936. RESULTS: the standardized mortality ratio in employed persons was low (0.59
      and 0.51 for men and women, respectively) and high in disability benefit
      recipients (2.31 and 1.66). The mortality in the early retirement benefit
      recipients (0.88 and 0.72) was in between the mortality for the disability
      benefit recipients and the employed persons. Disability benefit recipients had a
      high relative risk of death immediately after retirement. In early retirement
      recipients the relative risk of death increased with time since retirement.
      CONCLUSIONS: Disability benefit was mainly gained by persons with poor health. In
      contrast, the increasing mortality of the early retirement recipients is
      consistent with an adverse effect on health of retirement itself, but may also be
      due to the cessation of health selection in the group of disability benefit
      recipients after retirement. It is difficult to disentangle the effects of a
      change in activity following retirement from the effects of an earlier health
      associated selection into the two retirement schemes.

PMID- 12227980
TI  - Life expectancy in the province of Halland, Sweden, 1911-50: the progress of
      public health in a long-living population.
AB  - BACKGROUND: Life expectancy in Sweden is currently one of the longest in the
      world. The population of Halland has the longest life expectancy in Sweden. AIM:
      Life expectancy in the province of Halland and Sweden as a whole during 1911-50
      was studied and the findings are discussed in the light of local historical data.
      METHOD: A trend analysis of risk ratio of death and life expectancy for Halland
      and Sweden was done for the period 1911-50 with regard to calendar year, age, and
      sex using a Poisson model. RESULTS: The risk ratio between Halland and Sweden was
      0.83 for 1911 and 0.76 for 1950. The risk ratio of death for women was lower
      compared with men and this difference increased over time. At the start of the
      study period life expectancy for men and women was higher in Halland (58.5 and
      60.1 years, respectively) compared with Sweden (54.7 and 56.4 years,
      respectively) with a difference of approximately 3.8 years. At the end of the
      study period this difference in life expectancy for men and women in Halland
      (71.3 and 72.3 years, respectively) and the nation (68.0 and 69.2 years,
      respectively) had decreased to approximately 3.3 years. CONCLUSION: The long life
      expectancy seen in Halland today can be traced back to the early twentieth
      century. The starting point for this development seems to be a lower infant
      mortality in Halland compared with Sweden as a nation during the 1880-90. The
      basis for this might have been a greater increase of food production during the
      whole nineteenth century as well as other socioeconomic characteristics of
      Halland compared with the rest of the country.

PMID- 12227981
TI  - Revise the review process of the Cochrane collaboration.

PMID- 12227984
TI  - Prevention vs. treatment and the future of HIV medical care.

PMID- 12227985
TI  - Human immunodeficiency virus infection unresponsive to highly active
      antiretroviral therapy: denial of poor medication adherence or recalcitrant
      infection?
AB  - Poor clinical and virologic response to combination antiretroviral therapy for
      human immunodeficiency virus (HIV) infection may stem from a variety of factors
      including poor medication adherence, development of drug-resistant HIV strains,
      drug interactions, efflux pumps, and unfavorable pharmacokinetics. Diagnosing
      nonadherence to medication is particularly challenging. We present a case of lack
      of response to antiretroviral therapy in a patient who denied problems with
      medication adherence. The patient underwent a variety of objective examinations,
      all of which suggested poor medication adherence was responsible for his
      nonresponse to antiretrovirals. An approach to evaluating patients for causes of
      poor response to antiretroviral therapy and nonadherence and implications for
      clinical practice are discussed.

PMID- 12227986
TI  - Human immunodeficiency virus-related anemia of chronic disease: relationship to
      hematologic, immune, and iron metabolism parameters, and lack of association with
      serum interferon-gamma levels.
AB  - Anemia of chronic disease (ACD) is frequent in patients with human
      immunodeficiency virus (HIV) and its etiology is multifactorial. In a group of
      111 patients with HIV, 19 were diagnosed with ACD. Parameters related to iron
      metabolism, such as serum iron (SI), serum ferritin (SF), and soluble transferrin
      receptor (sTfR) were correlated to levels of interferon-gamma (IFN-gamma) and
      results compared to a group of 42 nonanemic patients with HIV. Measurements of
      erythropoietin (EPO), CD4/CD8 T-cell ratio, and reticulocyte count (RTC) were
      determined to verify aspects related to severity of disease and bone marrow
      response. The results showed higher SF concentrations in ACD patients and normal
      or slightly increased sTfR measurements in both groups. There was no correlation
      between IFN-gamma and SF and between IFN-gamma and sTfR determinations. Lower
      CD4/CD8 values were obtained in ACD, and an inverse correlation was observed
      between IFN-gamma and CD4/CD8 in groups with and without anemia. RTC counts and
      EPO concentrations were similar in both groups: immature RTC were increased in
      patients with anemia, indicating an apparent attempt of marrow response to
      compensate the increased demand. Our data showed no correlation between IFN-gamma
      levels and iron disturbances in ACD, but results reinforced the observation of
      enhanced immunologic system deterioration in patients with HIV and ACD.

PMID- 12227987
TI  - Vaginitis: case reports and brief review.
AB  - Vaginitis is the most frequently gynecologic diagnosis encountered by physicians
      who provide primary care to women. Accurate diagnosis can be elusive,
      complicating treatment. Most experts believe that up to 90% of vaginitis cases
      are secondary to bacterial vaginosis, vulvo-vaginal candidiasis, and
      trichomoniasis. The diagnosis of vaginitis is based on the patient's symptoms,
      the physical examination, the findings of microscopic examination of the wetmount
      and potassium hydroxide (KOH) preparations, and the results of the pH litmus
      test. Additional cultures and testing may be needed for difficult-to-diagnose
      cases.

PMID- 12227988
TI  - Guidelines for using body composition measurement in patients with human
      immunodeficiency virus infection.
AB  - Wasting remains a significant condition of human immunodeficiency virus (HIV)
      infection despite antiretroviral treatment. Early identification requires the
      measurement of various body composition parameters, particularly body cell mass
      (BCM). Anthropometry may provide some useful information. Cost and complexity
      issues make many body composition techniques unsuitable for the clinical setting.
      Bioelectrical impedance analysis (BIA) may be the best method available to
      caregivers for monitoring serial changes in BCM over time and for determining the
      occurrence of wasting. It is not useful, however, for detecting body composition
      changes in patients with fat redistribution syndromes. Portability, low cost,
      ease of use, and patient acceptance make anthropometry and BIA ideally suited for
      the clinical setting.

PMID- 12227989
TI  - Evaluation of a human immunodeficiency virus rule out tuberculosis critical
      pathway as an intervention to decrease nosocomial transmission of tuberculosis in
      the inpatient setting.
AB  - Nosocomial transmission of Mycobacterium tuberculosis (TB) is a recognized risk
      in health care settings, and is a particular concern in settings where human
      immunodeficiency virus (HIV)-infected persons receive care. TB control guidelines
      have been effective in prevention of nosocomial TB outbreaks and protection of
      patients and health care workers. In 1993 a South Florida academic medical center
      noted an increase in TB cases, particularly in HIV-infected persons who had been
      inpatients. A multidisciplinary team developed an HIV Rule Out TB Critical
      Pathway as an intervention to deter nosocomial transmission of TB. The pathway
      was implemented in 1995 on the Special Immunology/Infectious Disease (SI/ID)
      inpatient unit. This paper describes an evaluation study conducted to determine
      the effectiveness of the pathway as an intervention to deter nosocomial TB in
      relation to two areas: (1) early identification of HIV-infected patients with
      potential TB, followed by immediate placement in respiratory isolation and (2)
      protection of SI/ID unit personnel from occupational TB exposure. A retrospective
      review was conducted in June 1999 on the medical records of all patients who had
      been placed on the HIV Rule Out TB Critical Pathway from 1995-1998. A review was
      also done of the medical center's confirmed TB cases, and employee health records
      for tuberculin skin testing (TST) of employees during this time period. The
      review demonstrated that all HIV-infected patients with confirmed TB had been
      identified, placed on the pathway and admitted to respiratory isolation at the
      onset of hospital admission, deterring the potential for a nosocomial TB
      outbreak. However, in 1998 two SI/ID staff converted from a nonreactive to a
      reactive TST. Although the pathway was only partially successful in TB protection
      for staff members, other factors may have caused the TST conversions. A study
      recommendation is that institutions develop an HIV Rule Out TB Critical Pathway,
      along with a Rule Out TB Pathway for patients who are not HIV-infected but
      present with symptoms that may be indicative of TB infection.

PMID- 12227990
TI  - Imaging HIV/AIDS. Burkitt's lymphoma.
AB  - Imaging is often vital in the diagnosis and staging of acquired immune deficiency
      syndrome (AIDS) patients with regard to infections and malignancies. Non
      Hodgkin's lymphoma is an AIDS-defining illness and a common AIDS-related
      malignancy. These lymphomas are usually high-grade immunoblastic, primary central
      nervous system (CNS) or Burkitt's, and occasionally Hodgkin's. In Europe and
      North America, Burkitt's lymphoma occurs vastly more often in AIDS. Images of
      three widely varied cases of AIDS-related Burkitt's lymphoma reflect its
      radiologic features.

PMID- 12227994
TI  - A species conserving genetic algorithm for multimodal function optimization.
AB  - This paper introduces a new technique called species conservation for evolving
      parallel subpopulations. The technique is based on the concept of dividing the
      population into several species according to their similarity. Each of these
      species is built around a dominating individual called the species seed. Species
      seeds found in the current generation are saved (conserved) by moving them into
      the next generation. Our technique has proved to be very effective in finding
      multiple solutions of multimodal optimization problems. We demonstrate this by
      applying it to a set of test problems, including some problems known to be
      deceptive to genetic algorithms.

PMID- 12227992
TI  - Public unconcerned over herpes.

PMID- 12227991
TI  - Tenofovir gel studied.

PMID- 12227995
TI  - Modeling the dynamics of ant colony optimization.
AB  - The dynamics of Ant Colony Optimization (ACO) algorithms is studied using a
      deterministic model that assumes an average expected behavior of the algorithms.
      The ACO optimization metaheuristic is an iterative approach, where in every
      iteration, artificial ants construct solutions randomly but guided by pheromone
      information stemming from former ants that found good solutions. The behavior of
      ACO algorithms and the ACO model are analyzed for certain types of permutation
      problems. It is shown analytically that the decisions of an ant are influenced in
      an intriguing way by the use of the pheromone information and the properties of
      the pheromone matrix. This explains why ACO algorithms can show a complex dynamic
      behavior even when there is only one ant per iteration and no competition occurs.
      The ACO model is used to describe the algorithm behavior as a combination of
      situations with different degrees of competition between the ants. This helps to
      better understand the dynamics of the algorithm when there are several ants per
      iteration as is always the case when using ACO algorithms for optimization.
      Simulations are done to compare the behavior of the ACO model with the ACO
      algorithm. Results show that the deterministic model describes essential features
      of the dynamics of ACO algorithms quite accurately, while other aspects of the
      algorithms behavior cannot be found in the model.

PMID- 12227996
TI  - Combining convergence and diversity in evolutionary multiobjective optimization.
AB  - Over the past few years, the research on evolutionary algorithms has demonstrated
      their niche in solving multiobjective optimization problems, where the goal is to
      find a number of Pareto-optimal solutions in a single simulation run. Many
      studies have depicted different ways evolutionary algorithms can progress towards
      the Pareto-optimal set with a widely spread distribution of solutions. However,
      none of the multiobjective evolutionary algorithms (MOEAs) has a proof of
      convergence to the true Pareto-optimal solutions with a wide diversity among the
      solutions. In this paper, we discuss why a number of earlier MOEAs do not have
      such properties. Based on the concept of epsilon-dominance, new archiving
      strategies are proposed that overcome this fundamental problem and provably lead
      to MOEAs that have both the desired convergence and distribution properties. A
      number of modifications to the baseline algorithm are also suggested. The concept
      of epsilon-dominance introduced in this paper is practical and should make the
      proposed algorithms useful to researchers and practitioners alike.

PMID- 12227998
TI  - The effects of topological inaccuracy in evolutionary trees on the phylogenetic
      comparative method of independent contrasts.
AB  - Computer simulations were used to test the effect of increasing phylogenetic
      topological inaccuracy on the results obtained from correlation tests of
      independent contrasts. Predictably, increasing the number of disruptions in the
      tree increases the likelihood of significant error in the r values produced and
      in the statistical conclusions drawn from the analysis. However, the position of
      the disruption in the tree is important: Disruptions closer to the tips of the
      tree have a greater effect than do disruptions that are close to the root of the
      tree. Independent contrasts derived from inaccurate topologies are more likely to
      lead to erroneous conclusions when there is a true significant relationship
      between the variables being tested (i.e., they tend to be conservative). The
      results also suggest that random phylogenies perform no better than
      nonphylogenetic analyses and, under certain conditions, may perform even worse
      than analyses using raw species data. Therefore, the use of random phylogenies is
      not beneficial in the absence of knowledge of the true phylogeny.

PMID- 12227997
TI  - Improved sampling of the pareto-front in multiobjective genetic optimizations by
      steady-state evolution: a pareto converging genetic algorithm.
AB  - Previous work on multiobjective genetic algorithms has been focused on preventing
      genetic drift and the issue of convergence has been given little attention. In
      this paper, we present a simple steady-state strategy, Pareto Converging Genetic
      Algorithm (PCGA), which naturally samples the solution space and ensures
      population advancement towards the Pareto-front. PCGA eliminates the need for
      sharing/niching and thus minimizes heuristically chosen parameters and
      procedures. A systematic approach based on histograms of rank is introduced for
      assessing convergence to the Pareto-front, which, by definition, is unknown in
      most real search problems. We argue that there is always a certain inheritance of
      genetic material belonging to a population, and there is unlikely to be any
      significant gain beyond some point; a stopping criterion where terminating the
      computation is suggested. For further encouraging diversity and competition, a
      nonmigrating island model may optionally be used; this approach is particularly
      suited to many difficult (real-world) problems, which have a tendency to get
      stuck at (unknown) local minima. Results on three benchmark problems are
      presented and compared with those of earlier approaches. PCGA is found to produce
      diverse sampling of the Pareto-front without niching and with significantly less
      computational effort.

PMID- 12227999
TI  - Analysis of color spectra in comparative evolutionary studies: molecular
      phylogeny and habitat adaptation in the St. Vincent Anole (Anolis trinitatis).
AB  - The use of color (as distinct from color pattern) in comparative evolutionary
      studies is important, and objective, independent characters are needed. A new
      method was employed to investigate geographic color variation in the small
      arboreal lizard Anolis trinitatis on the island of St. Vincent. The simple delta
      analysis (based on the difference between eigenvector coefficients for adjacent
      regions of the spectrum) is aimed at increasing the objectivity with which a
      spectrum is cut into independent segments and does not predetermine segment width
      or number. There are distinct habitat types within this small island and distinct
      phylogenetic lineages (based on a kilobase of cytochrome b sequence) within this
      species. A series of matrix correspondence (Mantel) tests indicate that aspects
      of color are associated with habitat type (e.g., green dorsum in rain forest
      lizards), molecular phylogeny, or both. Hence, both adaptation by selection and
      historical processes are implicated as causes of geographic variation in color.
      The dewlap variation (e.g., strong ultraviolet reflectance in some Atlantic
      coastal sites) is very pronounced and, contrary to some expectations, may result
      in reproductive isolation even within small Lesser Antillean islands.

PMID- 12228000
TI  - Perils of paralogy: using HSP70 genes for inferring organismal phylogenies.
AB  - Conserved genes have found their way into the mainstream of molecular
      systematics. Many of these genes are members of multigene families. A difficulty
      with using single genes of multigene families for phylogenetic inference is that
      genes from one species may be paralogous to those from another taxon. We focus
      attention on this problem using heat shock 70 (HSP70) genes. Using polymerase
      chain reaction techniques with genomic DNA, we isolated and sequenced 123
      distinct sequences from 12 species of sharks. Phylogenetic analysis indicated
      that the sequences cluster with constituitively expressed cytoplasmic heat shock
      like genes. Three highly divergent gene clades were sampled. A number of similar
      sequences were sampled from each species within each distinct gene clade.
      Comparison of published species trees with an HSP70 gene tree inferred using
      Bayesian phylogenetic analysis revealed several cases of gene duplication and
      differential sorting of gene lineages within this group of sharks. Gene tree
      parsimony based on the objective criteria of duplication and losses showed that
      previously published hypotheses of species relationships and two novel hypothesis
      based on Bayesian phylogenetics were concordant with the history of HSP70 gene
      duplication and loss. By contrast, two published hypotheses based on
      morphological data were not significantly different from the null hypothesis of a
      random association between species relatedness and the HSP70 gene tree. These
      results suggest that gene tree parsimony using data from multigene families can
      be used for inferring species relationships or testing published alternative
      hypotheses. More importantly, the results suggest that systematic studies relying
      on phylogenetic inferences from HSP70 genes may by plagued by unrecognized
      paralogy of sampled genes. Our results underscore the distinction between gene
      and species trees and highlight an underappreciated source of discordance between
      gene trees and organismal phylogeny, i.e., unrecognized paralogy of sampled
      genes.

PMID- 12228001
TI  - Increased taxon sampling greatly reduces phylogenetic error.
AB  - Several authors have argued recently that extensive taxon sampling has a positive
      and important effect on the accuracy of phylogenetic estimates. However, other
      authors have argued that there is little benefit of extensive taxon sampling, and
      so phylogenetic problems can or should be reduced to a few exemplar taxa as a
      means of reducing the computational complexity of the phylogenetic analysis. In
      this paper we examined five aspects of study design that may have led to these
      different perspectives. First, we considered the measurement of phylogenetic
      error across a wide range of taxon sample sizes, and conclude that the expected
      error based on randomly selecting trees (which varies by taxon sample size) must
      be considered in evaluating error in studies of the effects of taxon sampling.
      Second, we addressed the scope of the phylogenetic problems defined by different
      samples of taxa, and argue that phylogenetic scope needs to be considered in
      evaluating the importance of taxon-sampling strategies. Third, we examined the
      claim that fast and simple tree searches are as effective as more thorough
      searches at finding near-optimal trees that minimize error. We show that a more
      complete search of tree space reduces phylogenetic error, especially as the taxon
      sample size increases. Fourth, we examined the effects of simple versus complex
      simulation models on taxonomic sampling studies. Although benefits of taxon
      sampling are apparent for all models, data generated under more complex models of
      evolution produce higher overall levels of error and show greater positive
      effects of increased taxon sampling. Fifth, we asked if different phylogenetic
      optimality criteria show different effects of taxon sampling. Although we found
      strong differences in effectiveness of different optimality criteria as a
      function of taxon sample size, increased taxon sampling improved the results from
      all the common optimality criteria. Nonetheless, the method that showed the
      lowest overall performance (minimum evolution) also showed the least improvement
      from increased taxon sampling. Taking each of these results into account re
      enforces the conclusion that increased sampling of taxa is one of the most
      important ways to increase overall phylogenetic accuracy.

PMID- 12228003
TI  - Examining Basal avian divergences with mitochondrial sequences: model complexity,
      taxon sampling, and sequence length.

PMID- 12228002
TI  - A genomic schism in birds revealed by phylogenetic analysis of DNA strings.
AB  - The molecular systematics of vertebrates has been based entirely on alignments of
      primary structures of macromolecules; however, higher order features of DNA
      sequences not used in traditional studies also contain valuable phylogenetic
      information. Recent molecular data sets conflict over the phylogenetic placement
      of flightless birds (ratites - paleognaths), but placement of this clade
      critically influences interpretation of character change in birds. To help
      resolve this issue, we applied a new bioinformatics approach to the largest
      molecular data set currently available. We distilled nearly one megabase (1
      million base pairs) of heterogeneous avian genomic DNA from 20 birds and an
      alligator into genomic signatures, defined as the complete set of frequencies of
      short sequence motifs (strings), thereby providing a way to directly compare
      higher order features of nonhomologous DNA sequences. Phylogenetic analysis and
      principal component analysis of the signatures strongly support the traditional
      hypothesis of basal ratites and monophyly of the nonratite birds (neognaths) and
      imply that ratite genomes are linguistically primitive within birds, despite
      their base compositional similarity to neognath genomes. Our analyses show
      further that the phylogenetic signal of genomic signatures are strongest among
      deep splits within vertebrates. Despite clear problems with phylogenetic analysis
      of genomic signatures, our study raises intriguing issues about the biological
      and genomic differences that fundamentally differentiate paleognaths and
      neognaths.

PMID- 12228004
TI  - The utility of the incongruence length difference test.

PMID- 12228006
TI  - Units in biogeography.

PMID- 12228005
TI  - Phylogeny reconstruction and functional constraints in organellar genomes:
      plastid atpB and rbcL sequences versus animal mitochondrion.

PMID- 12228007
TI  - Resolution of a supertree/supermatrix paradox.

PMID- 12228009
TI  - Recombinant adenovirus vector activates and protects human monocyte-derived
      dendritic cells from apoptosis.
AB  - The aim of this study was to examine the effect of two of the most commonly used
      viral vectors, that is, retrovirus and adenovirus, on the antigen presentation of
      dendritic cells (DCs). DCs were generated from CD34(+) hematopoietic precursors
      and CD14(+) monocytes of the same prostate cancer patients. Adenoviral
      transduction of monocyte-derived DCs (MO-DCs) resulted in upregulation of CD80,
      CD86, and CD83 expression. Adenovirus-transduced MO-DCs were also more potent
      stimulators of allogeneic lymphocytes, produced increased amounts of the
      cytokines tumor necrosis factor alpha and interleukin 12 p70, and exhibited
      increased expression of NF-kappaB and antiapoptotic molecules Bcl-X(L) and Bcl-2.
      Enhanced expression of the antiapoptotic molecules correlated with increased
      resistance of adenovirus-transduced MO-DCs to spontaneous as well as Fas-mediated
      cell death. In contrast to the adenoviral construct, no significant transduction
      of MO-DCs with the retrovirus could be obtained. Transduction of CD34(+) cell
      derived DCs with the retrovirus or the adenovirus did not significantly alter
      expression of the costimulatory molecules or cytokines studied. At lower
      stimulation ratios, CD34(+) cell-derived DCs transduced with retrovirus were less
      potent in their ability to stimulate allogeneic lymphocytes in comparison with
      nontransduced DCs. Our results indicate that adenoviral vectors may be more
      suitable for gene delivery to DCs for immunotherapy.

PMID- 12228008
TI  - Increased taxon sampling is advantageous for phylogenetic inference.

PMID- 12228010
TI  - Safety, tolerability, and lack of antibody responses after administration of a
      PfCSP DNA malaria vaccine via needle or needle-free jet injection, and comparison
      of intramuscular and combination intramuscular/intradermal routes.
AB  - Introduction of a new vaccine requires choosing a delivery system that provides
      safe administration and the desired level of immunogenicity. The safety,
      tolerability, and immunogenicity of three monthly 2.5-mg doses of a PfCSP DNA
      vaccine were evaluated in healthy volunteers as administered intramuscularly (IM)
      by needle, IM by jet injection (Biojector or IM/intradermally (ID) by jet
      injection. Vaccine administration was well-tolerated. Adverse events were
      primarily mild and limited to the site of injection (98%). Jet injections (either
      IM or ID) were associated with approximately twice as many adverse events per
      immunization as needle IM, but nevertheless were strongly and consistently
      preferred in opinion polls taken during the study. No volunteers had clinically
      significant biochemical or hematologic changes or detectable anti-dsDNA
      antibodies. In conclusion, the injection of Plasmodium falciparum
      circumsporozoite (PfCSP) DNA vaccine appeared to be safe and well-tolerated when
      administered by any of the three modes of delivery. However, despite improved
      antibody responses following both jet injection and ID delivery in animal models,
      no antibodies could be detected in volunteers by immunofluorescence antibody test
      (IFAT) or enzyme-linked immunosorbent assay (ELISA) after DNA vaccination.

PMID- 12228011
TI  - Adenovirus-mediated expression of glucokinase in the liver as an adjuvant
      treatment for type 1 diabetes.
AB  - Glucokinase (GK) plays a crucial role in hepatic glucose disposal. Its activity
      is decreased in patients with maturity-onset diabetes of the young and in some
      animal models of diabetes. We investigated the feasibility of manipulating GK
      expression as an adjuvant treatment for type 1 diabetes, using an E1/E3-deleted
      adenoviral vector (Ad.EF1(alpha)GK) delivered to the liver of streptozotocin
      induced type 1 diabetic rats. First, we studied the metabolic impact of
      constitutive glucokinase expression in the absence of insulin. Normal blood
      glucose levels were observed after gene transfer, and glucose tolerance was
      substantially enhanced compared with diabetic control animals, suggesting that
      hepatic GK expression is a feasible mechanism to enhance glucose disposal. In a
      second study we administered Ad.EF1(alpha)GK together with subcutaneous insulin
      injections to determine whether the combined action of insulin plus GK activity
      would provide better glucose homeostasis than insulin treatment alone. This
      combination approach resulted in constant, near-normal glucose values under fed
      conditions. Furthermore, the animals stayed in the normoglycemic range after an
      overnight fast, indicating that the risk to develop hypoglycemia is not increased
      by expression of GK. Alterations of other metabolic routes were observed,
      suggesting that insulin-regulated expression of GK may be necessary to use the
      strategy as a treatment of type 1 diabetes.

PMID- 12228012
TI  - Oral administration of recombinant adeno-associated virus elicits human
      immunodeficiency virus-specific immune responses.
AB  - Oral vaccines can induce both systemic and mucosal immunity. Mucosal immunity,
      especially regional cell-mediated immunity, plays an important role in protecting
      individuals from infectious diseases such as acquired immunodeficiency syndrome.
      In this study, a recombinant adeno-associated virus vector expressing human
      immunodeficiency virus type 1 env gene (AAV-HIV) was orally administered to
      BALB/c mice. Systemic and regional immunity was induced in the mice. Furthermore,
      the immunization significantly reduced viral load after an intrarectal challenge
      with a recombinant vaccinia virus expressing HIV env gene. Moreover, we also show
      that dendritic cells might contribute to the AAV-HIV vector-induced immune
      responses.

PMID- 12228013
TI  - The canine factor VIII 3'-untranslated region and a concatemeric hepatocyte
      nuclear factor 1 regulatory element enhance factor VIII transgene expression in
      vivo.
AB  - If gene therapy is to be an effective treatment modality for hemophilia A,
      therapeutic levels and tissue-restricted expression of factor VIII (FVIII) must
      be achieved through optimization of transgene expression. To this end, we
      incorporated three types of sequence elements into a canine B domain-deleted
      FVIII transgene cassette and individually evaluated their effect on FVIII
      transgene expression. Functional FVIII activity was initially assessed in vitro
      and hydrodynamic injection of the different transgene constructs into mice was
      subsequently used as a model to compare in vivo expression of the various
      modified transgenes. Our results demonstrate that in vitro transgene expression
      is, in these studies, not a good predictor of in vivo transgene performance. In
      vivo analysis of a hybrid tissue-restricted promoter element, consisting of a
      concatemer of five hepatocyte nuclear factor 1 (HNF-1) consensus-binding motifs
      juxtaposed to the human FVIII proximal promoter, indicates that it is as
      efficient at mediating expression of the FVIII protein as the cytomegalovirus
      promoter. Addition of the full-length canine FVIII 3'-UTR also enhances transgene
      expression of FVIII in vivo. Sequence analysis of the canine FVIII 3'-UTR and
      human FVIII 3'-UTR indicates that the former lacks instability sequences and may
      therefore be more effective in stabilizing FVIII mRNA. Subsequent inclusion of
      FVIII introns 16 and 17 into the natural locations of the transgene disrupted
      mRNA processing and abolished expression of the FVIII protein. Introduction of
      intron 17 proximal to the FVIII cDNA did not enhance in vivo expression of canine
      FVIII from the transgene.

PMID- 12228014
TI  - Plasma vascular endothelial growth factor (VEGF) levels after intramuscular and
      intramyocardial gene transfer of VEGF-1 plasmid DNA.
AB  - The purpose of this study was to document the kinetics of vascular endothelial
      growth factor (VEGF) protein release into the systemic circulation after phVEGF
      gene transfer for therapeutic angiogenesis. VEGF plasma levels were measured by
      ELISA in 64 patients undergoing gene transfer of plasmid DNA: intramuscular in 34
      patients with peripheral artery disease, and intramyocardial in 30 patients with
      coronary disease. Baseline plasma VEGF was highly variable and not normally
      distributed. After intramuscular gene transfer, median plasma VEGF rose slightly,
      although significantly, by 7 days (38 to 41 pg/ml, p < 0.05), but was not
      different from baseline at 14, 21, or 28 days. After intramyocardial gene
      transfer, median plasma VEGF levels were significantly elevated compared with
      baseline on days 2, 3, and 7 (39, 38, and 45 pg/ml, respectively, each p < 0.05
      vs. baseline value of 21 pg/ml). Day 7 plasma levels did not differ significantly
      as a function of phVEGF dose, or between intramyocardial and intramuscular
      injections (1.8 and 1.3 times baseline levels, respectively, p = 0.6), despite an
      almost 10-fold difference in mean phVEGF dose. Intramuscular and intramyocardial
      phVEGF injections result in significant, although modest, elevations of
      circulating gene product for <14 days, with no relationship to injected dose.
      While a statistically significant increase in circulating VEGF level can provide
      evidence of successful gene transfer for groups of patients, interpretation of
      results for individual subjects is complicated by wide variation in baseline VEGF
      and low circulating levels compared with baseline after gene transfer.

PMID- 12228015
TI  - Immune response to fetal calf serum by two adenosine deaminase-deficient patients
      after T cell gene therapy.
AB  - The first approved clinical gene therapy trial for adenosine deaminase (ADA)
      deficiency employed autologous T cells grown in fetal calf serum (FCS)
      supplemented medium and transduced with a retroviral vector (LASN) also produced
      in the presence of FCS. Ten years after their enrollment, both patients have
      circulating T cells containing vector DNA. However, whereas approximately 20% of
      the circulating T cells from patient 1 are still vector positive, less than 1% of
      patient 2's T cells have detectable vector. This difference appears to be not
      only a function of the original transduction efficiency and cell expansion
      capability in vitro, but also of the immune response that patient 2 developed to
      FCS components during the course of her treatment. In this study, serum samples
      from each patient were tested for antibodies to FCS by enzyme-linked
      immunosorbent assay and anti-FCS responses were demonstrated in both patients.
      Analysis of immunoglobulin classes revealed comparable levels of IgA and IgM anti
      FCS titers. Patient 2, however, had significantly higher IgG responses to FCS
      than did patient 1. Investigation of the development of anti-FCS responses by IgG
      subclasses indicated that there was a different pattern in the development of IgG
      immunity to FCS between the two patients. In addition, significant antibody
      response to bovine lipoprotein was detected in patient 2, but not in patient 1 or
      in control samples. These findings suggest that the unique immune response
      mounted by patient 2 may have influenced the outcome of the gene transfer
      treatments in this patient.

PMID- 12228016
TI  - Gene transfer of a chimeric trans-activator is immunogenic and results in short
      lived transgene expression.
AB  - Pharmacologic gene regulation is a key technology, necessary to achieve safe,
      long-term gene transfer. The approaches described in the scientific literature
      all share in common the creation of artificial transcription factors by fusing a
      DNA-binding domain, a drug-binding domain and a transcription activation domain.
      These transcription factors activate the transgene expression upon binding of the
      pharmacologic agent (antibiotics of the tetracycline family, insect hormone,
      progesterone antagonist, or immunosuppressor drug) to the drug-binding domain.
      The major limitations to the use of these systems for human gene and cell
      therapies are the toxicity of the inducer molecule and the immunogenicity of the
      chimeric transcription factor. Thus, the gene regulation systems should operate
      with clinically approved drugs with safety records that do not conflict with the
      therapeutic gene expression regimen. This work focuses on the characterization of
      the immunogenicity of a tetracycline-activated transcription factor commonly used
      in preclinical gene therapy, rtTA2-M2, and its impact on reporter gene
      expression. We demonstrate that intramuscular injection of plasmid or adenoviral
      vectors encoding rtTA-M2 in outbred primates generates a cellular and humoral
      immune response to this transcription factor. The immune response to rtTA2-M2
      blunts the duration of the expression the rtTA2-M2-controlled transgene in
      primates, presumably by destruction of the cells that coexpress rtTA2-M2 and the
      reporter or therapeutic gene. This immune response may result directly from the
      vectors used in this study, which prompts the development of new gene transfer
      vectors enabling safe and efficient pharmacologic gene regulation in clinic.

PMID- 12228019
TI  - Double modification of adenovirus fiber with RGD and polylysine motifs improves
      coxsackievirus-adenovirus receptor-independent gene transfer efficiency.
AB  - Adenoviral vectors based on serotype 5 (Ad5) have been widely used to deliver
      therapeutic genes to different organs and tissues. However, many tissues are
      poorly infected with Ad5 because of low-level expression of its primary receptor,
      coxsackievirus-adenovirus receptor (CAR). Two motifs, RGD and polylysine (pK7),
      have been shown to enhance Ad5 infection via CAR-independent pathways when
      incorporated into fiber separately. Because the two motifs bind to different cell
      surface proteins (RGD motif binds to integrins, and pK7 binds to heparan sulfate
      containing receptors), we hypothesized that the two motifs function additively to
      improve gene transfer efficiency. In this study, we sought to improve infectivity
      of Ad5 by incorporating both RGD and pK7 motifs into fiber. We created an Ad5
      vector containing an RGD motif in the HI loop and a pK7 motif at the C terminus
      of fiber (Ad5.RGD.pK7). Compared with unmodified and singly modified Ad5 vectors
      Ad5.RGD and Ad5.pK7, the doubly modified Ad5 demonstrated the highest infectivity
      in both CAR-positive and CAR-negative cells. The enhanced infectivity appeared to
      be mediated by additive effects of the two motifs. More importantly, Ad5.RGD.pK7
      lost the natural CAR-dependent pathway while employing novel targeting
      mechanisms. This strategy thus may be used to overcome CAR deficiency and to
      achieve vector retargeting.

PMID- 12228017
TI  - Gene transfer of a human insulin-like growth factor I cDNA enhances tissue
      engineering of cartilage.
AB  - The repair of articular cartilage lesions remains a clinical problem. Two novel
      approaches to cartilage formation, gene transfer and tissue engineering, have
      been limited by short-term transgene expression in transplanted chondrocytes and
      inability to deliver regulatory signals to engineered tissues according to
      specific temporal and spatial patterns. We tested the hypothesis that the
      transfer of a cDNA encoding the human insulin-like growth factor I (IGF-I) can
      provide sustained gene expression in cell-polymer constructs in vitro and in vivo
      and enhance the structural and functional properties of tissue-engineered
      cartilage. Bovine articular chondrocytes genetically modified to overexpress
      human IGF-I were seeded into polymer scaffolds, cultured in bioreactors in serum
      free medium, and implanted subcutaneously in nude mice; constructs based on
      nontransfected or lacZ-transfected chondrocytes served as controls. Transgene
      expression was maintained throughout the duration of the study, more than 4 weeks
      in vitro followed by an additional 10 days either in vitro or in vivo.
      Chondrogenesis progressed toward the formation of cartilaginous tissue that was
      characterized by the presence of glycosaminoglycans, aggrecan, and type II
      collagen, and the absence of type I collagen. IGF-I constructs contained
      increased amounts of glycosaminoglycans and collagen and confined-compression
      equilibrium moduli as compared with controls; all groups had subnormal
      cellularity. The amounts of glycosaminoglycans and collagen per unit DNA in IGF-I
      constructs were markedly higher than in constructs cultured in serum-supplemented
      medium or native cartilage. This enhancement of chondrogenesis by spatially
      defined overexpression of human IGF-I suggests that cartilage tissue engineering
      based on genetically modified chondrocytes may be advantageous as compared with
      either gene transfer or tissue engineering alone.

PMID- 12228018
TI  - Delivery of alpha- and beta-sarcoglycan by recombinant adeno-associated virus:
      efficient rescue of muscle, but differential toxicity.
AB  - The sarcoglycanopathies are a group of four autosomal recessive limb girdle
      muscular dystrophies (LGMD 2D, 2E, 2C, and 2F), caused by mutations of the alpha
      , beta-, gamma-, or delta-sarcoglycan genes, respectively. The delta-sarcoglycan
      deficient hamster has been the most utilized model for gene delivery to muscle by
      recombinant adeno-associated virus (AAV) vectors; however, human patients with
      delta-sarcoglycan deficiency are exceedingly rare, with only two patients
      described in the United States. Here, we report construction and use of AAV
      vectors expressing either alpha- or beta-sarcoglycan, the genes responsible for
      the most common forms of the human sarcoglycanopathies. Both vectors showed
      successful short-term genetic, biochemical, and histological rescue of both alpha
      and beta-sarcoglycan-deficient mouse muscle. However, comparison of persistence
      of expression in 51 injected mice showed substantial differences between AAV
      alpha-sarcoglycan (alpha-SG) and beta-sarcoglycan (beta-SG) vectors. AAV-beta-SG
      showed long-term expression with no decrease in expression for more than 21
      months after injection, whereas AAV-alpha-SG showed a dramatic loss of positive
      fibers between 28 and 41 days post-injection (p = 0.006). Loss of immunopositive
      myofibers was correlated with significant inflammatory cell infiltrate, primarily
      macrophages. To determine whether the loss of alpha-sarcoglycan-positive fibers
      was due to an immune response or cytotoxic effect of alpha-sarcoglycan
      overexpression, severe combined immunodeficient (SCID) mouse muscle was assayed
      for cytotoxicity after injection with AAV-alpha-SG, AAV-beta-SG, or phosphate
      buffered saline. The results were consistent with overexpression of alpha
      sarcoglycan causing significant cytotoxicity. The cytotoxicity of alpha
      sarcoglycan, and not beta- or delta-sarcoglycan overexpression, was consistent
      with biochemical studies of the hierarchical order of assembly of the sarcoglycan
      complex. Our data suggest that even closely related proteins might require
      different levels of expression to avoid toxicity and achieve long-term tissue
      rescue.

PMID- 12228020
TI  - A microinjected COL7A1-PAC vector restores synthesis of intact procollagen VII in
      a dystrophic epidermolysis bullosa keratinocyte cell line.
AB  - Dystrophic epidermolysis bullosa (DEB) comprises a family of inherited blistering
      skin disorders for which no corrective therapy currently exists. In the most
      severe form, the Hallopeau-Siemens subtype (RDEB-HS), the epidermal adhesion
      protein collagen VII is absent from the skin as a consequence of null mutations
      in the COL7A1 gene. In order to develop an ex vivo gene therapy approach for DEB,
      we aimed to restore expression of intact procollagen VII in RDEB-HS
      keratinocytes. The entire human COL7A1 locus in a P1-derived artificial
      chromosome (PAC) was transferred to RDEB-HS keratinocytes by microinjection,
      after which sustained biosynthesis and secretion of procollagen VII was detected
      for 1 year in vitro. Protein chemical analysis demonstrated that the chain
      composition, domain structure, N-glycosylation and protein folding of the newly
      produced procollagen VII were similar, if not identical, to its authentic
      counterpart, indicating that transgenic procollagen VII was structurally normal.
      These data demonstrate a "proof of principle" for genomic DNA vectors as a means
      of restoring collagen VII production in RDEB-HS skin and help develop future gene
      therapy protocols.

PMID- 12228023
TI  - Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomized
      controlled trial.

PMID- 12228024
TI  - Pathogenesis, Therapy, and Prevention of Meningococcal Sepsis.
AB  - Neisseria meningitidis (meningococcus), an exclusive pathogen of humans, is the
      cause of sepsis (meningococcemia) and meningitis, often in otherwise healthy
      individuals. Several hundred thousand cases of meningococcal disease occur
      worldwide each year, a number that is frequently accentuated by epidemic
      outbreaks. In recent years, significant advances, fueled by new molecular
      approaches and genome sequencing projects, have improved our understanding of the
      pathogenesis of meningococcal disease and have led to progress in the development
      of the next generation of meningococcal vaccines. However, the mortality of
      meningococcal disease remains 10% to 15% for all cases, and is up to 40% in
      patients with severe sepsis. This review summarizes current knowledge of the
      pathogenesis, therapy, and prevention of meningococcal disease with emphasis on
      meningococcal sepsis.

PMID- 12228025
TI  - The Pathophysiology and Treatment of Candida Sepsis.
AB  - Sepsis can occur during disseminated candidiasis, but its pathogenesis differs
      from that caused by typical prokaryotic pathogens. Complex interactions between
      defects in host defense and "relative" virulence factors expressed by Candida
      lead to dissemination of the saprophyte to parenchymal organs, and subsequently
      to onset of multiorgan failure. This review focuses first on the pathophysiology
      of Candida sepsis, detailing current understanding of host-pathogen interactions.
      We then consider the choice of antifungal and supportive treatments.

PMID- 12228026
TI  - The Genomic Aspect of Virulence, Sepsis, and Resistance to Killing Mechanisms in
      Staphylococcus aureus.
AB  - Staphylococcus aureus is widely appreciated as a pathogen, despite the fact that
      this microorganism is usually a benign colonizer of the host, rarely if ever
      causing infection. However, this bacterium, in response to changing environments,
      will occasionally switch from a commensal to a lethal pathogen. S. aureus uses an
      array of two-component signal transduction systems, winged-helix transcription
      proteins, and alternate sigma factor to create an intricate network of regulation
      in response to environmental change/stimuli. The interactions between members of
      this large cast of regulatory elements are beginning to be appreciated.
      Predicated upon recent genomic data, this review focuses on how this regulatory
      apparatus functions to control the expression of the multitude of virulence
      factors this "Jekyl and Hyde" organism produces.

PMID- 12228027
TI  - Randomized prospective controlled trial of recombinant granulocyte colony
      stimulating factor as adjunctive therapy for limb-threatening diabetic foot
      infection.

PMID- 12228028
TI  - Skin and Soft Tissue Infections in Injection Drug Users.
AB  - Skin and soft tissue infections (SSTIs) are common among injection drug users
      (IDUs). Subcutaneous and intramuscular injection ("skin-popping") and the
      injection of "speedballs" (a mixture of heroin and cocaine) are important risk
      factors for SSTIs in this patient population. Female IDUs appear to be at greater
      risk of SSTIs than male IDUs, probably because of more difficult venous access.
      There are conflicting data regarding the impact of HIV and human T-cell
      lymphotrophic virus II infection on the risk of SSTIs in IDUs; however, an
      expanding body of evidence suggests that immunosuppressive effects of the drugs
      themselves may play a role. Most information regarding the microbiology of SSTIs
      in IDUs comes from data on skin and subcutaneous abscesses, where Staphylococcus
      aureus and organisms that originate from the oral flora predominate. Clonal
      outbreaks and uncommon infections including tetanus, wound botulism, and a
      sepsis/myonecrosis syndrome due to Clostridium species have been recently
      reported in IDUs.

PMID- 12228029
TI  - Nasal Carriage of Staphylococcus aureus As a Risk Factor for Skin and Soft Tissue
      Infections.
AB  - Nasal carriage of Staphylococcus aureus is a major risk factor for the
      development of S. aureus infection, including skin and soft tissue infections and
      foreign body infections, such as catheter-associated bacteremia and peritonitis.
      In this article, we review the recent literature on S. aureus nasal carriage,
      including the emergence of methicillin- resistant S. aureus in the community, the
      pathophysiology of nasal carriage, and the epidemiology and prevention of S.
      aureus infections associated with nasal carriage.

PMID- 12228030
TI  - The Role of Fluoroquinolones in the Treatment of Skin and Soft Tissue Infection.
AB  - Skin and soft tissue infections vary widely in their nature and severity, and
      their nomenclature is complex. Most are readily recognized and easily treated,
      but more severe infections may masquerade in forms similar to those of more
      innocent infections, causing delay in diagnosis and treatment that may result in
      loss of limb or life. Antimicrobial therapy is clearly beneficial for both
      recovery from these infections as well as preventing disease progression. The
      fluoroquinolones are potent broad-spectrum antimicrobial agents. The older
      fluoroquinolones mainly have excellent in vitro activity against gram-negative
      bacilli and borderline activity against clinically important gram-positive
      organisms, but newer fluoroquinolones were developed to have enhanced activity
      against both gram-positive and anaerobic organisms while retaining broad-spectrum
      anti-gram-negative activity. Several comparative trials using fluoroquinolones
      suggest that the efficacy of these agents is similar to that of b-lactam
      antimicrobial agents. Additional clinical trials are necessary to determine the
      overall role of newer fluoroquinolones as alternatives for skin and soft tissue
      infections.

PMID- 12228031
TI  - Treatment Options for Orthopedic Device-related Infections.
AB  - Though uncommon, prosthetic joint infections are a devastating complication of
      total joint replacement surgeries and are a cause of significant morbidity.
      Although complete removal of all foreign material followed by a prolonged course
      of directed antibiotic therapy is the optimal treatment for such infections, many
      factors, such as patient health, cost, available bone stock, and timing of
      infection influence the type of treatment that is chosen. We review the different
      treatment options for prosthetic joint infections, including surgical modalities
      and antibiotic choice, duration, and suppression.

PMID- 12228032
TI  - Long Bone Osteomyelitis.
AB  - Osteomyelitis is a complex disease that is often associated with high morbidity
      and considerable health care costs. Bacteremia, contiguous focuses of infection,
      penetrating trauma, or surgery are the major predisposing factors for this
      infection. Bone necrosis and bone destruction occur early in the course of
      osteomyelitis, leading to a chronic process and eliminating the host's ability to
      eradicate the pathogens. The presence of poorly vascularized tissues, the
      adherence to bone structures and implants, and a slow bacterial replication rate
      are recognized as important factors for the persistence of the infection.
      Treatment of osteomyelitis is particularly challenging and involves adequate
      antimicrobial therapy and surgical debridement of all necrotic bone and soft
      tissues. Antibiotic treatment is usually started on an empiric basis and then
      modified according to the results of cultures and sensitivity tests. Surgical
      treatment consists of debridement, obliteration of dead space, adequate soft
      tissue coverage, restoration of blood supply, and stabilization.

PMID- 12228033
TI  - Renal Dysfunction in HIV-1-infected Patients.
AB  - Improved therapy directed against opportunistic infection and HIV-1 itself has
      resulted in greatly enhanced patient survival in the past decade among patients
      infected with HIV-1. Since patients are living longer, HIV-1 infection is
      associated with a rising burden of kidney disease. Approximately 14% of black
      patients and 6% of white patients dying with HIV-1 infection in 1999 in the
      United States had renal disease. Overall, 10% of patients dying with HIV-1
      infection had renal failure. The most common glomerular diseases are focal
      segmental glomerulosclerosis and immune complex glomerulonephritis. Appropriate
      therapy for focal segmental glomerulosclerosis includes effective antiretroviral
      therapy and angiotensin antagonist medication. Drug toxicity is also common,
      often manifesting as electrolyte abnormalities, acute renal failure, interstitial
      nephritis, or nephrolithiasis. In particular, indinavir is associated with
      crystalluria, nephrolithiasis, interstitial nephritis, and lower urinary tract
      inflammation. Appropriate screening for renal disease and appropriate
      intervention will likely reduce the morbidity and mortality associated with
      progressive renal disease.

PMID- 12228034
TI  - The Role of CD4(+) and CD8(+) T Cells in Controlling HIV Infection.
AB  - Presently, it is thought that virus-specific T cells play a major role in
      restricting lentiviral replication and determining the rate of disease
      progression in humans. However, it remains unclear why this restriction fails in
      the majority of infected individuals. The major exception is a rare subgroup of
      HIV-infected long-term nonprogressors (LTNPs) who have been infected for
      approximately 20 years yet maintain normal CD4(+) T-cell counts and less than 50
      copies of viral RNA/mL of plasma. Although virus-specific cellular (CD4(+) and
      CD8(+) T lymphocytes) immune responses have been shown to exert some degree of in
      vivo control of HIV replication, the precise correlates of protective immunity
      differentiating LTNPs from patients with progressive disease remain unknown. A
      greater understanding of the components and magnitude of an effective immune
      response to HIV is an important step toward the development of effective vaccines
      and immunotherapies.

PMID- 12228035
TI  - Chronic Helicobacter infection of the human liver and bile are common and may
      trigger autoimmune disease.

PMID- 12228037
TI  - Radiation enteritis.
AB  - The frequent use of radiotherapy for abdominal and pelvic malignancies results in
      an increased risk of radiation enteritis. An increased understanding of the
      tissue response and the clinical features of radiation enteritis has led to
      advances in the prevention and management of this condition. Importantly,
      improvements in the delivery of radiotherapy, including techniques to reduce the
      amount of exposed small intestine in the radiation field, represent a critical
      strategy for prevention. Data indicate that radioprotectant agents have the
      potential to reduce intestinal mucosal injury and may be beneficial in reducing
      both acute and chronic side effects of radiotherapy.

PMID- 12228039
TI  - Food allergies.
AB  - Adverse reactions to foods are commonly implicated in the causation of ill
      health. However, foreign antigens, including food proteins and commensal microbes
      encountered in the gastrointestinal tract, are usually well tolerated. True food
      allergies, implying immune-mediated adverse responses to food antigens, do exist,
      however, and are especially common in infants and young children. Allergic
      reactions to food manifest clinically in a variety of presentations involving the
      gastrointestinal, cutaneous, and respiratory systems and in generalized reactions
      such as anaphylaxis. Both IgE-mediated and non-IgE-mediated immune mechanisms are
      recognized. Important advances in the clinical features underlying specific food
      hypersensitivity disorders are reviewed.

PMID- 12228040
TI  - Stents in the small intestine.
AB  - Stents represent an exciting development in the field of gastroenterology. Their
      use to maintain luminal patency in the pancreatobiliary system has been well
      established. Stents have also found a place in maintaining the patency of the
      esophagus. Recent developments have led to an increasing role for their use to
      decompress both the small and large intestine. In the small intestine they are
      often placed to palliate proximal obstruction in the duodenum or the very
      proximal jejunum resulting from various malignancies. Self-expandable metal
      stents are an attractive alternative to surgery, especially in patients with
      compromised performance status, and can be done safely as outpatient procedures.
      However, one should be aware of the associated risks and complications. With a
      proper understanding of the principles involved in stent placement one can safely
      undertake this procedure.

PMID- 12228038
TI  - Eosinophilic gastroenteritis.
AB  - Eosinophilic gastroenteritis is a rare gastrointestinal (GI) disorder of
      undetermined cause characterized by infiltration of eosinophils in the GI tract.
      Eosinophils accumulate in tissues and may release highly cytotoxic granular
      proteins, which cause severe tissue damage characteristic of eosinophilic
      gastroenteritis. Eotaxin may play a role in the recruitment of eosinophils into
      tissue in combination with chemoattractants and cytokines, including interleukin
      3 and 5 and granulocyte-macrophage colony-stimulating factor. Food allergy,
      especially in children, can be a triggering factor, and an amino acid-based diet
      may be helpful. Accumulation of eosinophils in the gut is a common feature in
      food-induced GI disorders that can be regulated through a complex molecular
      network involving Th2 cells, various cytokines, and chemokines. Eosinophilic
      gastroenteritis has a wide spectrum of clinical presentation depending on the
      site of involvement. It may be confused with irritable bowel syndrome or
      dyspepsia and, rarely, mimics pancreatitis or appendicitis. Diagnosis is
      important and is usually made by a pathologist. Eosinophilic gastroenteritis is a
      treatable disease; patients generally respond to steroid therapy, although
      relapse is common. Non-enteric-coated budesonide, a locally acting corticosteroid
      with little risk of adrenal suppression, may be substituted, although more
      experience is needed. Promising new drugs for eosinophilic gastroenteritis
      include montelukast, a selective leukotriene receptor antagonist, and suplaplast
      tosilate, a selective Th2 cytokine inhibitor with inhibitory effects on allergy
      induced eosinophilic infiltration and IgE production. Although it is likely a
      separate disease, more experience has accumulated, and an elimination or specific
      amino acid-based diet appears to be helpful in treatment.

PMID- 12228041
TI  - HIV1 and the gut in the era of highly active antiretroviral therapy.
AB  - The gut and its gut-associated lymphoid tissue serve as a preferential site for
      HIV1 entry, active viral replication, reservoir, and HIV-mediated CD4 cell
      apoptosis. The widespread use of highly active antiretroviral therapy (HAART) has
      resulted in a significant decrease in the incidence of opportunistic enteric
      pathogens as a consequence of immune recovery. Nonetheless, patients with
      advanced HIV1 disease who were recently diagnosed or have poor response to HAART
      can still suffer from opportunistic infections with pathogens such as
      Cryptosporidium, microsporidia, Isospora belli, Cyclospora cayetanensis,
      Mycobacterium avium complex, and cytomegalovirus, among others. This review
      describes the impact of HIV1 infection on gut immune function, the salient
      features of the most common opportunistic enteric pathogens and HIV-associated
      enteropathy, and the effects of immune reconstitution after introduction of
      HAART.

PMID- 12228044
TI  - Surgical management of colon cancer.
AB  - The primary mode of therapy for colon cancer continues to be surgery. Although
      little has changed in the technical aspects of colonic resection, a great deal of
      research has taken place to develop procedures that enhance staging of disease,
      optimize postoperative recovery, and improve outcomes in obstructed patients
      without compromising cancer-related morbidity and mortality. This review explores
      the current use of laparoscopy, sentinel node biopsy, intraoperative ultrasound,
      and colonic stents in the elective and emergent management of colon cancer.

PMID- 12228043
TI  - Basic concepts for genetic testing in common hereditary colorectal cancer
      syndromes.
AB  - Approximately 5% of colorectal cancers are associated with one of the autosomal
      dominant hereditary cancer syndromes. The two most common familial colon cancer
      syndromes are familial adenomatous polyposis (FAP) and hereditary nonpolyposis
      colorectal cancer (HNPCC). The causative mutation can be identified in many
      families with these syndromes by genetic testing of an affected individual. If an
      affected individual tests positive for a disease-causing mutation, genetic
      testing of unaffected, at-risk family members can be performed to determine
      whether they have inherited the cancer-susceptibility mutation, and a
      personalized cancer surveillance strategy can be devised. Genetic testing
      significantly enhances cancer risk assessment in these families. However, the
      complicated nature of result interpretation and the emotional impact of the
      result necessitate that testing be carried out in conjunction with patient
      education and informed consent by a physician who has a keen appreciation for the
      inherent challenges. This article describes the genetic testing strategy in HNPCC
      and FAP.

PMID- 12228045
TI  - Adjuvant chemotherapy for colorectal cancer.
AB  - Colorectal cancer is the second leading cause of cancer death in Western
      countries. If surgery remains the only cure, recurrence rates for colon cancer
      range from 30% to 60% for stage III tumors. Adjuvant chemotherapy is the standard
      treatment for stage III colon tumors and consists of monthly administration of
      bolus 5-fluorouracil and leucovorin for 5 consecutive days a month over a 6-month
      period (Mayo regimen). Adjuvant chemotherapy for stage II colon cancer remains
      controversial, and its administration is not routinely recommended except in
      certain high-risk and selected patients. Immunotherapy, new drug-based therapies
      or combinations, and cyclooxygenase-2 inhibitors are being tested in the adjuvant
      setting. Total mesorectum excision is now the gold standard surgical technique
      for rectal cancer resection, and this procedure has dramatically decreased local
      recurrence. Nevertheless, adjuvant chemoradiotherapy is commonly indicated in the
      United States. In Europe, neoadjuvant radiotherapy is recommended for stage II
      and III resectable rectal cancers; the role of chemotherapy remains mostly
      investigational.

PMID- 12228046
TI  - New developments in the diagnosis and treatment of irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a common disorder with major health status and
      economic effects. Symptom criteria are of paramount importance in diagnosis, but
      differences among the Manning, Rome I, and Rome II criteria may lead to variable
      identification of people with the disorder. Practice guidelines are based on
      evidence and, to a greater degree, on consensus; therefore, experts vary on the
      specifics of ordering particular diagnostic tests. There is an overlap of IBS
      symptoms with those of celiac sprue, and selected patients should be tested for
      the latter disease. Symptom confusion with biliary pain and overlap with chronic
      pelvic pain could contribute to the predisposition of IBS patients to undergo
      cholecystectomy and hysterectomy. Development and documentation of effective
      therapy has been difficult, but depending on the selection of subgroups, there is
      evidence for usefulness of smooth muscle relaxants, loperamide, and
      antidepressants. Various forms of psychological therapy and new serotonin
      modulating agents seem especially promising. The placebo effect of the physician
      patient relationship has important therapeutic benefit.

PMID- 12228048
TI  - Neurohumoral regulation of arterial pressure in hemorrhage and heart failure.

PMID- 12228047
TI  - Comparative models and biological stress.

PMID- 12228049
TI  - Arterial baroreflex function and cardiovascular variability: interactions and
      implications.
AB  - The arterial baroreflex contributes importantly to the short-term regulation of
      blood pressure and cardiovascular variability. A number of factors (including
      reflex, humoral, behavioral, and environmental) may influence gain and
      effectiveness of the baroreflex, as well as cardiovascular variability. Many
      central neural structures are also involved in the regulation of the
      cardiovascular system and contribute to the integrity of the baroreflex.
      Consequently, brain injuries or ischemia may induce baroreflex impairment and
      deranged cardiovascular variability. Baroreflex dysfunction and deranged
      cardiovascular variability are also common findings in cardiovascular disease. A
      blunted baroreflex gain and impaired heart rate variability are predictive of
      poor outcome in patients with heart failure and myocardial infarction and may
      represent an early index of autonomic activation in left ventricular dysfunction.
      The mechanisms mediating these relationships are not well understood and may in
      part be the result of cardiac structural changes and/or altered central neural
      processing of baroreflex signals.

PMID- 12228050
TI  - Effect of NOS inhibition on central response to atrial distension during
      pregnancy.
AB  - Atrial distension increases c-fos expression in the paraventricular nucleus of
      virgin, but not pregnant, rats. We proposed that nitric oxide (NO), biosynthesis
      of which increases during pregnancy, blunts this reflex and that blocking NO
      biosynthesis would restore the response. Female rats were implanted with
      indwelling intracardiac balloons. On day 14 of pregnancy, osmotic minipumps
      containing either D- or N(G)-nitro-L-arginine methyl ester (L-NAME) (120 mg/2 ml
      at 10 microg/min) were implanted. On day 20, the rats were infused with saline (3
      ml/h) with or without atrial balloon inflation (1 h). The brains were then
      processed for quantitation of c-fos expression. In the virgin rats, and in the
      pregnant rats treated with L-NAME, atrial distension significantly increased
      hypothalamic c-fos expression. In the pregnant animals treated with D-NAME, the
      response was greatly attenuated. NO had no effect on the increase in atrial
      receptor afferent discharge (single-fiber recordings) elicited by atrial
      distension. We conclude that, during pregnancy, NO attenuates central processing
      of the reflex response to atrial distension but does not alter the transducer
      properties of the volume receptors.

PMID- 12228052
TI  - Diuretic response to acute hypertension is blunted during angiotensin II clamp.
AB  - Acute hypertension inhibits proximal tubule (PT) fluid reabsorption. The
      resultant increase in end proximal flow rate provides the error signal to mediate
      tubuloglomerular feedback autoregulation of renal blood flow and glomerular
      filtration rate and suppresses renal renin secretion. To test whether the
      suppression of the renin-angiotensin system during acute hypertension affects the
      magnitude of the inhibition of PT fluid and sodium reabsorption, plasma ANG II
      levels were clamped by infusion of the angiotensin-converting enzyme (ACE)
      inhibitor captopril (12 microg/min) and ANG II after pretreatment with the
      bradykinin B(2) receptor blocker HOE-140 (100 microg/kg bolus). Because ACE also
      degrades bradykinin, HOE-140 was included to block effect of accumulating
      vasodilatory bradykinins during captopril infusion. HOE-140 increased the
      sensitivity of arterial blood pressure to ANG II: after captopril infusion
      without HOE-140, 20 ng x kg(-1) x min(-1) ANG II had no pressor effect, whereas
      with HOE-140, 20 ng x kg(-1) x min(-1) ANG II increased blood pressure from 104
      +/- 4 to 140 +/- 6 mmHg. ANG II infused at 2 ng x kg(-1) x min(-1) had no pressor
      effect after captopril and HOE-140 infusion ("ANG II clamp"). When blood pressure
      was acutely increased 50-60 mmHg by arterial constriction without ANG II clamp,
      urine output and endogenous lithium clearance increased 4.0- and 6.7-fold,
      respectively. With ANG II clamp, the effects of acute hypertension were reduced
      50%: urine output and endogenous lithium clearance increased two- and threefold,
      respectively. We conclude that HOE-140, an inhibitor of the B(2) receptor,
      potentiates the sensitivity of arterial pressure to ANG II and that clamping
      systemic ANG II levels during acute hypertension blunts the magnitude of the
      pressure diuretic response.

PMID- 12228053
TI  - Chemical activation of C(1)-C(2) spinal neurons modulates activity of thoracic
      respiratory interneurons in rats.
AB  - Discharge patterns of thoracic dorsal horn neurons are influenced by chemical
      activation of cell bodies in cervical spinal segments C(1)-C(2). The present aim
      was to examine whether such activation would specifically affect thoracic
      respiratory interneurons (TRINs) of the deep dorsal horn and intermediate zone in
      pentobarbital sodium-anesthetized, paralyzed, artificially ventilated rats. We
      also characterized discharge patterns and pathways of TRIN activation in rats. A
      total of 77 cells were classified as TRINs by location, continued burst activity
      related to phrenic discharge when the respirator was stopped, and lack of
      antidromic response from selected pathways. A variety of respiration-phased
      discharge patterns was documented whose pathways were interrupted by ipsilateral
      C(1) transection. Glutamate pledgets (1 M, 1 min) on the dorsal surface of the
      spinal cord inhibited 22/49, excited 15/49, or excited/inhibited 3/49 tested
      cells. Incidence of responses did not depend on whether the phase of TRIN
      discharge was inspiratory, expiratory, or biphasic. Phrenic nerve activity was
      unaffected by chemical activation of C(1)-C(2) in this preparation. Besides
      supraspinal input, TRIN activity may be influenced by upper cervical modulatory
      pathways.

PMID- 12228051
TI  - Simulated microgravity impairs aldosterone secretion in rats: possible
      involvement of adrenomedullin.
AB  - The prolonged exposure to microgravity (MG) or simulated MG (SMG) has been
      reported to cause hypotension, mainly due to reduced vascular contractility, and
      dysregulation of fluid and electrolyte balance. However, the mechanism(s)
      involved in these MG- or SMG-induced effects is not yet completely elucidated.
      Hence, we investigated in the rat the effect of prolonged (15 day) SMG, in the
      form of hindlimb unweighting, on the renin-angiotensin-aldosterone system (RAAS),
      as well as on atrial natriuretic peptide (ANP) and adrenomedullin (ADM), two
      hypotensive peptides that play a major role in the regulation of RAAS activity by
      inhibiting adrenal aldosterone secretion. SMG caused a mild hypotension in rats,
      associated with the blockade of body weight gain. Plasma aldosterone
      concentration and basal and agonist-stimulated in vitro aldosterone secretion
      from adrenal slices were decreased, and plasma renin activity was moderately
      increased. Neither Na(+) and K(+) serum concentrations nor ACTH and
      corticosterone blood levels were significantly affected. Plasma ANP concentration
      did not display significant alterations, while ADM blood concentration underwent
      a marked rise. The administration of the ADM-receptor antagonist ADM-(22-52)
      during the last 3 days of hindlimb unweighting reversed the SMG-induced
      hypotension and hypoaldosteronism. Collectively, these findings allow us to
      suggest that prolonged SMG impairs RAAS activity in rats, through a mechanism
      probably involving upregulation of the ADM system. Both hypoaldosteronism and
      increased ADM secretion may contribute to the development of hypotension during
      prolonged exposure to SMG.

PMID- 12228054
TI  - Mechanical strain regulation of the chicken glypican-4 gene expression in the
      avian eggshell gland.
AB  - Comparison of RNA fingerprinting of the avian eggshell gland (ESG) without and
      with an egg revealed upregulation of a 382-bp cDNA fragment that showed high
      homology to the mammalian glypican 4 (GPC-4). The gene sequence revealed a
      conserved glypican signature, a glycosyl phosphatidyl inositol-anchorage site,
      and cystein residues, most of which were conserved. GPC-4 was expressed in the
      ESG in a circadian fashion only during the period of eggshell calcification, when
      maximal mechanical strain was imposed. Removal of the egg just before to its
      entry into the ESG, with consequent elimination of the mechanical strain, caused
      reduction in the gene expression. Artificial application of the mechanical strain
      induced expression of the GPC-4 gene that was related to the level of the strain.
      GPC-4 expression was strain dependent in other parts of the oviduct. In the ESG,
      GPC-4 was expressed exclusively by the glandular epithelium and not by the
      pseudostratified epithelium facing the lumen. In summary, we cloned the avian
      homologue of GPC-4, established its pattern of expression in the avian ESG, and
      demonstrated for the first time that this gene is regulated by mechanical strain.

PMID- 12228056
TI  - Does neonatal cerebrospinal fluid absorption occur via arachnoid projections or
      extracranial lymphatics?
AB  - Arachnoid villi and granulations are thought to represent the primary sites where
      cerebrospinal fluid (CSF) is absorbed. However, these structures do not appear to
      exist in the fetus but begin to develop around the time of birth and increase in
      number with age. With the use of a constant pressure-perfusion system in 2- to 6
      day-old lambs, we observed that global CSF transport (0.012 +/- 0.003 ml x min(
      1) x cmH(2)O(-1)) and CSF outflow resistance (96.5 +/- 17.8 cmH(2)O x ml(-1) x
      min) were very similar to comparable measures in adult animals despite the
      relative paucity of arachnoid villi at this stage of development. In the neonate,
      the recovery patterns of a radioactive protein CSF tracer in various lymph nodes
      and tissues indicated that CSF transport occurred through multiple lymphatic
      pathways. An especially important route was transport through the cribriform
      plate into extracranial lymphatics located in the nasal submucosa. To investigate
      the importance of the cribriform route in cranial CSF clearance, the cranial CSF
      compartment was isolated surgically from its spinal counterpart. When the
      cribriform plate was sealed extracranially under these conditions, CSF transport
      was impaired significantly. These data demonstrate an essential function for
      lymphatics in neonatal CSF transport and imply that arachnoid projections may
      play a limited role earlier in development.

PMID- 12228055
TI  - A role for cyclooxygenase-2 in lipopolysaccharide-induced anorexia in rats.
AB  - Because nonselective cycloooxygenase (COX) inhibition attenuated anorexia after
      lipopolysaccharide (LPS) administration, we tested the ability of resveratrol
      (2.5, 10, and 40 mg/kg) and NS-398 (2.5, 10, and 40 mg/kg), selective inhibitors
      of the two COX isoforms COX-1 and -2, respectively, to attenuate LPS (100
      microg/kg ip)-induced anorexia. NS-398 (10 and 40 mg/kg) administered with LPS at
      lights out attenuated LPS-induced anorexia, whereas resveratrol at all doses
      tested did not. Because prostaglandin (PG) E(2) is considered the major
      metabolite synthesized by COX, we measured plasma and cerebrospinal fluid (CSF)
      PGE(2) levels after LPS administration. LPS induced a time-dependent increase of
      PGE(2) in CSF but not in plasma. NS-398 (5, 10, and 40 mg/kg) blocked the LPS
      induced increase in CSF PGE(2), whereas resveratrol (10 mg/kg) did not. These
      results support a role of COX-2 in mediating the anorectic response to peripheral
      LPS and point at PGE(2) as a potential neuromodulator involved in this response.

PMID- 12228057
TI  - Capsaicin-sensitive adrenal sensory fibers participate in compensatory adrenal
      growth in rats.
AB  - Compensatory adrenal growth, in which one gland undergoes hyperplasia after
      removal of the other, is mediated by a neural reflex. In the present studies, a
      method employing capsaicin to selectively remove adrenal sensory fibers was
      developed and applied to determine whether adrenal capsaicin-sensitive fibers
      participate in compensatory adrenal growth. The splanchnic nerves of anesthetized
      male rats were treated with capsaicin or vehicle. Capsaicin treatment selectively
      removed adrenal calcitonin gene-related peptide-positive fibers. One week after
      drug treatment, rats underwent left adrenalectomy or sham surgery and recovered
      for 5 days. Capsaicin treatment bilaterally or to the left splanchnic nerve alone
      (i.e., the afferent nerve in the reflex) impaired compensatory adrenal growth at
      5 days compared with vehicle controls, whereas capsaicin treatment to the right
      splanchnic nerve alone did not affect growth. Moreover, left adrenalectomy
      induced c-Fos immunolabeling in ipsilateral dorsal spinal cord that was prevented
      by capsaicin treatment. These data suggest that adrenal capsaicin-sensitive
      afferent nerves participate in compensatory adrenal growth and that this effect
      is primarily on the afferent limb of the reflex.

PMID- 12228058
TI  - Crocodile transthyretin: structure, function, and evolution.
AB  - Structure and function were studied for Crocodylus porosus transthyretin
      (crocTTR), an important intermediate in TTR evolution. The cDNA for crocTTR mRNA
      was cloned and sequenced and the amino acid sequence of crocTTR was deduced. In
      contrast to mammalian TTRs, but similar to avian and lizard TTRs, the subunit of
      crocTTR had a long and hydrophobic NH(2)-terminal region. Different from the
      situation in mammals, triiodothyronine (T(3)) was bound by crocTTR with higher
      affinity than thyroxine (T(4)). Recombinant crocTTR and a chimeric construct,
      with the NH(2)-terminal region of crocTTR being replaced by that of Xenopus
      laevis TTR, were synthesized in the yeast Pichia pastoris. Analysis of the
      affinity of the chimeric TTRs showed that the NH(2)-terminal region modulates
      T(4) and T(3) binding characteristics of TTR. The structural differences of the
      NH(2)-terminal regions of reptilian and amphibian TTRs were caused by a shift in
      splice sites at the 5' end of exon 2. The comparison of crocodile and other
      vertebrate TTRs shows that TTR evolution is an example for positive Darwinian
      evolution and identifies its molecular mechanism.

PMID- 12228059
TI  - Anterior paraventricular thalamus modulates light-induced phase shifts in
      circadian rhythmicity in rats.
AB  - The reciprocal connections between the paraventricular thalamic nucleus (PVT) and
      the suprachiasmatic nuclei suggest that PVT may participate in the regulation of
      circadian rhythms. We studied in rats the effect of lesions of the anterior and
      midposterior regions of the PVT on phase shifts of drinking circadian rhythm
      induced by light pulses at circadian times 6, 12, and 23, as well as the phase
      shifts produced by electrical or glutamatergic stimulation of the anterior PVT at
      the same circadian times. Lesion of the anterior PVT abolishes the advances
      induced by light during late subjective night, whereas midposterior PVT lesions
      did not affect the phase shifts. Electrical stimulation or glutamate injections
      in the anterior PVT mimic the phase-shifting effects of light pulses. These
      results indicate the participation of the anterior PVT as a modulator of
      entrainment of circadian rhythms to light.

PMID- 12228061
TI  - Influence of hypoxia and of hypoxemia on the development of cardiac activity in
      zebrafish larvae.
AB  - Cardiac activity and anaerobic metabolism were analyzed in zebrafish larvae
      raised under normoxia (PO(2) = 20 kPa) and under chronic hypoxia (PO(2) = 10 kPa)
      at three different temperatures (25, 28, and 31 degrees C). Heart rate increased
      with development and with temperature. Under normoxia, cardiac output increased
      significantly at high temperature (31 degrees C), but not at 28 or at 25 degrees
      C. Under chronic hypoxia, however, heart rate as well as cardiac output increased
      at all temperatures in larvae at about hatching time or shortly thereafter.
      Cardiac activity of larvae raised for 2 wk after fertilization with a reduced
      hemoglobin oxygen-carrying capacity in their blood (hypoxemia; due to the
      presence of CO or of phenylhydrazine in the incubation water) was not different
      from control animals. Whole body lactate content of these animals did not
      increase. Thus there was no indication of a stimulated anaerobic energy
      metabolism. The increase in cardiac activity observed during hypoxia suggests
      that at about hatching time receptors are present that sense hypoxic conditions,
      and this information can be used to induce a stimulation of convective oxygen
      transport to compensate for a reduction in bulk oxygen diffusion in the face of a
      reduced oxygen gradient between environmental water and tissues. Under normoxia,
      however, the PO(2) gradient between environmental water and tissues and
      diffusional oxygen transport assure sufficient oxygen supply even if hemoglobin
      oxygen transport in the blood is severely impaired. Thus, under normoxic
      conditions and with a normal metabolic rate of the tissues, convective oxygen
      transport is not required until approximately 2 wk after fertilization.

PMID- 12228062
TI  - Gene expression analysis in burn wounds of rats.
AB  - The events occurring early in the burn wound trigger a sequence of local and
      systemic responses that influence cell and tissue survival and, consequently,
      wound healing and recovery. Using high-density oligonucleotide arrays we
      identified gene expression patterns in skin samples taken from a region of injury
      in the burn rat model. The associated genomic events include the differential
      expression of genes involved in cell survival and death, cell growth regulation,
      cell metabolism, inflammation, and immune response. The functional gene cluster
      detected and their time appearance matched the time sequence known to occur in
      burn wound healing.

PMID- 12228060
TI  - Expression of dopaminergic receptors in the hypothalamus of lean and obese Zucker
      rats and food intake.
AB  - As revealed by previous microdialysis studies, basal and food intake-accompanied
      dopamine release significantly differs in the hypothalamus of obese vs. lean
      Zucker rats. In the present study, we determined whether dopaminergic receptors
      are also compromised in obesity. Dopaminergic D(1) and D(2) receptor mRNA
      expression was studied in the ventromedial hypothalamus (VMH), lateral
      hypothalamic area (LHA), and the adenohypophysis (AH) of obese and lean Zucker
      rats using RT-PCR technique. In obese Zucker rats, we found an upregulation of
      D(1) receptor mRNA in the VMH and AH and a downregulation in the LHA, whereas
      D(2) receptor mRNA was downregulated in both the VMH and LHA, but not changed in
      the AH, compared with lean rats. Also, an increase of D(1) receptor staining was
      seen in the paraventricular nucleus of obese rats by immunohistochemistry. We
      selected the VMH to test if the observed changes in the dopamine receptor
      expression of obese rats induce behavioral sensitization to dopamine as expressed
      by hyperphagia. The overnight food-deprived rats received a single VMH injection
      (10 nmol) of sulpiride (D(2) receptor antagonist) or saline as control, then food
      was provided and 1-h food intake was measured. Food intake after sulpiride vs.
      saline injection was greater in obese rats but was not different in lean rats.
      Our data suggest that downregulation of D(2) receptor in the hypothalamus at
      least in the VMH induces behavior sensitization for having large meals. Low D(2)
      receptor expression may be causal for an exaggerated dopamine release observed in
      obese rats during food ingestion and for reduced satiety feedback effect of
      dopamine. High level of D(1) receptor expression in the VMH and low in the LHA
      may also contribute to the specific feeding pattern in obese rats represented by
      large meal size and low meal number.

PMID- 12228063
TI  - Respiratory cycle timing and fast inspiratory discharge rhythms in the adult
      decerebrate rat.
AB  - In supracollicular decerebrate paralyzed adult rats, neural respiration was
      monitored by bilateral phrenic recordings. In the study of respiratory cycle
      timing, the effects of vagal afferent input (lung inflation) on respiratory phase
      durations resembled those seen in decerebrate cats. 1) Withholding lung inflation
      during neural inspiration (I) produced lengthening of I phase duration by 46%
      (mean, n = 11). 2) Maintaining lung inflation during neural expiration (E)
      produced lengthening of E phase duration by 112% (mean, n = 4). In the study of
      fast rhythms in inspiratory discharges, phrenic nerve autospectra and bilateral
      (left-right) phrenic coherences in 16 rats revealed two types of fast rhythm: 1)
      high-frequency oscillation (HFO), which had significant coherence peaks (n = 9,
      range 106-160 Hz, mean 132 Hz); and 2) medium-frequency oscillation (MFO), which
      had autospectral peaks but no distinct coherence peaks (n = 11, range 46-96 Hz,
      mean 66 Hz). These rhythms resembled MFOs and HFOs in the decerebrate cat, but
      the modal frequency range was about twice as large. In addition, these frequency
      values differed markedly from the 20-40 Hz of the rhythms found in earlier
      studies in neonatal in vitro preparations; the difference may be due to
      developmental immaturity.

PMID- 12228065
TI  - Membrane potential controls calcium entry into descending vasa recta pericytes.
AB  - We tested the hypothesis that constriction of descending vasa recta (DVR) is
      mediated by voltage-gated calcium entry. K(+) channel blockade with BaCl(2) (1
      mM) or TEACl (30 mM) depolarized DVR smooth muscle/pericytes and constricted in
      vitro-perfused vessels. Pericyte depolarization by 100 mM extracellular KCl
      constricted DVR and increased pericyte intracellular Ca(2+) ([Ca(2+)](i)). The
      K(ATP) channel opener pinacidil (10(-7)-10(-4) M) hyperpolarized resting
      pericytes, repolarized pericytes previously depolarized by ANG II (10(-8) M), and
      vasodilated DVR. The DVR vasodilator bradykinin (10(-7) M) also reversed ANG II
      depolarization. The L-type Ca(2+) channel blocker diltiazem vasodilated ANG II
      (10(-8) M)- or KCl (100 mM)-preconstricted DVR, and the L-type agonist BayK 8644
      constricted DVR. The plateau phase of the pericyte [Ca(2+)](i) response to ANG II
      was inhibited by diltiazem. These data support the conclusion that DVR
      vasoreactivity is controlled through variation of membrane potential and voltage
      gated Ca(2+) entry into the pericyte cytoplasm.

PMID- 12228064
TI  - Reduced central leptin sensitivity in rats with diet-induced obesity.
AB  - On low-fat chow diet, rats prone to diet-induced obesity (DIO) have increased
      arcuate nucleus neuropeptide Y (NPY) expression but similar leptin levels
      compared with diet-resistant (DR) rats (19). Here, body weight and leptin levels
      rose in DIO rats, and they defended their higher body weight after only 1 wk on a
      31% fat high-energy (HE) diet. However, DIO NPY expression did not fall to DR
      levels until 4 wk when plasma leptin was 168% of DR levels. When switched to
      chow, DIO rats lost carcass fat (18). By 10 wk, leptin levels fell to 148% and
      NPY expression again rose to 150% of DR levels. During 4 wk of food restriction,
      DIO leptin fell by approximately 50% while NPY increased by 30%. While both
      returned to control levels by 8 wk, DIO rats still regained all lost weight when
      fed ad libitum. Finally, the anorexic effect of intracerebroventricular leptin
      (10 microg) was inversely correlated with subsequent 3-wk weight gain on HE diet.
      Thus NPY expression and food intake are less sensitive to the leptin's
      suppressive effects in DIO rats. While this may predispose them to develop DIO,
      it does not fully explain their defense of a higher body weight on HE diet.

PMID- 12228066
TI  - Desmin cytoskeletal modifications after a bout of eccentric exercise in the rat.
AB  - Desmin content and immunohistochemical appearance were measured in tibialis
      anterior muscles of rats subjected to a single bout of 30 eccentric contractions
      (ECs). Ankle torque was measured before EC and at various recovery times, after
      which immunohistochemical and immunoblot analyses were performed. Torque
      decreased by approximately 50% immediately after EC and fully recovered 168 h
      later (P < 0.001). Loss of desmin staining was maximal 12 h after EC and
      recovered by 72 h. Immunoblots unexpectedly demonstrated a significant increase
      in the desmin-to-actin ratio by 72 h after EC (P < 0.01) and was still increasing
      after 168 h (P < 0.0001). These data demonstrate a relatively rapid qualitative
      loss of desmin immunostaining immediately after a single EC bout but a tremendous
      quantitative increase in desmin content 72-168 h later. This dynamic
      restructuring of the muscle's intermediate filament system may be involved in the
      mechanism of EC-induced muscle injury and may provide a structural explanation
      for the protective effects observed in muscle after a single EC bout.

PMID- 12228068
TI  - Angiotensin II receptor (type 1 and 2) expression peaks when placental growth is
      maximal in sheep.
AB  - In sheep, placental size is maximal by midgestation, but blood flow continues to
      increase until term. No nerves are present and ANG II is thought to be a major
      regulator of vascular tone. We hypothesized that angiotensin type 2 receptors
      (AT(2)) would predominate over type 1 (AT(1)) until late in gestation and be
      primarily expressed in the vasculature. Real-time PCR, hybridization
      histochemistry, and ligand-binding studies were performed on placentae and fetal
      membranes at 27, 45, 66 +/- 1, 100 +/- 4, 130, and 140 days of gestation (term
      approximately 150 days) to determine quantitative changes and localization. The
      maximum level of AT(1) expression occurred in the 45-day placenta and was located
      predominantly in the maternal stromal cells. AT(1) receptors were expressed in
      the endothelial cells of the chorion in the first half of pregnancy, where later
      in gestation, both AT(1) and AT(2) receptors were predominant in blood vessels.
      These results suggest that ANG II, via the AT(1) receptor, may have hitherto
      unsuspected important roles in the growth/function on the ovine placenta during
      the maximal growth phase.

PMID- 12228067
TI  - Expression and developmental regulation of the NMDA receptor subunits in the
      kidney and cardiovascular system.
AB  - Antagonists to the N-methyl-D-aspartate (NMDA) receptor bind to various
      extraneuronal tissues. We therefore assessed the expression of the main NMDA
      subunit, NR1, in various tissues. We demonstrate that NR1 appears to be most
      abundant in the rat kidney and heart. NR1 is present in total rat kidney, cortex,
      and medulla. Of the NR2 subunits, only the NR2C subunit protein is present in the
      kidney. The abundance of the NR1 subunit protein increases with kidney
      development. Both NR1 and NR2C are present in opossum kidney, Madin-Darby canine
      kidney, and LLC-PK(1) cells. Immunohistochemistry studies show that the NR1
      subunit is present in the renal proximal tubule. NR1 is abundant in the atrium
      and ventricle but is also expressed in the aorta and pulmonary artery. The NR2
      subunits are not expressed in the heart. NR1 subunit protein expression is
      constant throughout heart development. Finally, the NR1 subunit protein is
      expressed in heart cells (H9c2) grown in culture. These studies reveal the
      presence of the NMDA receptor in the kidney and the cardiovascular system.

PMID- 12228070
TI  - The general professional education of the physician: is four years enough time?

PMID- 12228069
TI  - Pendrin immunoreactivity in the gill epithelium of a euryhaline elasmobranch.
AB  - Pendrin is an anion exchanger in the cortical collecting duct of the mammalian
      nephron that appears to mediate apical Cl(-)/HCO3(-) exchange in bicarbonate
      secreting intercalated cells. The goals of this study were to determine 1) if
      pendrin immunoreactivity was present in the gills of a euryhaline elasmobranch
      (Atlantic stingray, Dasyatis sabina), and 2) if branchial pendrin
      immunoreactivity was influenced by environmental salinity. Immunoblots detected
      pendrin immunoreactivity in Atlantic stingray gills; pendrin immunoreactivity was
      greatest in freshwater stingrays compared with freshwater stingrays acclimated to
      seawater (seawater acclimated) and marine stingrays. Using immunohistochemistry,
      pendrin-positive cells were detected on both gill lamellae and interlamellar
      regions of freshwater stingrays but were more restricted to interlamellar regions
      in seawater-acclimated and marine stingray gills. Pendrin immunolabeling in
      freshwater stingray gills was more apical, discrete, and intense compared with
      seawater-acclimated and marine stingrays. Regardless of salinity, pendrin
      immunoreactivity occurred on the apical region of cells rich with basolateral
      vacuolar-proton-ATPase, and not in Na(+)-K(+)-ATPase-rich cells. We suggest that
      a pendrin-like transporter may contribute to apical Cl(-)/HCO3(-) exchange in
      gills of Atlantic stingrays from both freshwater and marine environments.

PMID- 12228071
TI  - The challenge of educating physicians about complementary and alternative
      medicine.
AB  - The rapid growth of complementary/alternative medicine (CAM) predated both the
      1992 establishment of the Office of Alternative Medicine at the National
      Institutes of Health and the release of Dr. David Eisenberg's 1993 groundbreaking
      article on the widespread use of CAM. Since these two watershed events, the use
      of nontraditional medical modalities has seen exponential expansion. Most
      physicians are not prepared to respond knowledgeably about CAM modalities, and,
      indeed, sorting out the viable CAM modalities can be a difficult task. Additional
      factors are poor and inadequate dialogue between physicians and CAM
      practitioners, doubts about CAM practitioners' competence, a lack of readily
      identifiable and recognizable qualifications of such practitioners, and the risk
      of offering unrealistic hope of a cure. All these factors place the patient in a
      sometimes perilously uncertain position. Incorporating systematic presentation of
      CAM information into the curricula of medical schools would provide future
      physicians the necessary tools and knowledge to enable their patients to use CAM
      modalities appropriately, with limited risks.

PMID- 12228072
TI  - Integrative medical education: development and implementation of a comprehensive
      curriculum at the University of Arizona.
AB  - Dissatisfaction with the U.S. health care system is increasing despite impressive
      technologic advances. This dissatisfaction is one factor that has led patients to
      seek out complementary and alternative medicine (CAM) and led medical schools to
      start teaching CAM. This paper focuses on the University of Arizona's approach to
      developing and implementing a comprehensive curriculum in integrative medicine.
      Integrative medicine is defined much more broadly than CAM. It is healing
      oriented medicine that reemphasizes the relationship between patient and
      physician, and integrates the best of complementary and alternative medicine with
      the best of conventional medicine. Since its inception in 1996, the Program in
      Integrative Medicine (PIM) has grown to include a two-year residential fellowship
      that educates four fellows each year, a distance learning associate fellowship
      that educates 50 physicians each year, medical student and resident rotations,
      continuing medical and professional education, an NIH-supported research
      department, and an active outreach program to facilitate the international
      development of integrative medicine. The paper describes the PIM curriculum,
      educational programs, clinical education, goals, and results. Future strategies
      for assessing competency and credentialing professionals are suggested.

PMID- 12228074
TI  - Integrative medicine and the search for the best practice of medicine.

PMID- 12228075
TI  - Complementary and alternative medicine and the need for evidence-based criticism.

PMID- 12228081
TI  - Thank you, Mr. Stewart.

PMID- 12228082
TI  - The teaching of complementary and alternative medicine in U.S. medical schools: a
      survey of course directors.
AB  - PURPOSE: The number of U.S. medical schools offering courses in complementary and
      alternative medicine (CAM) has risen sharply in recent years. This study gauged
      the current state of CAM instruction by gathering details about the specific
      topics being taught and the objectives behind the instruction. METHOD: Data were
      collected from questionnaires mailed to 123 CAM course directors at 74 U.S.
      medical schools. RESULTS: Questionnaires were returned by 73 course directors at
      53 schools. The topics most often being taught were acupuncture (76.7%), herbs
      and botanicals (69.9%), meditation and relaxation (65.8%),
      spirituality/faith/prayer (64.4%), chiropractic (60.3%), homeopathy (57.5%), and
      nutrition and diets (50.7%). The amounts of instructional time devoted to
      individual CAM topics varied widely, but most received about two contact hours.
      The "typical" CAM course was sponsored by a clinical department as an elective,
      was most likely to be taught in the first or fourth year of medical school, and
      had fewer than 20 contact hours of instruction. Most of the courses (78.1%) were
      taught by individuals identified as being CAM practitioners or prescribes of CAM
      therapies. Few of the courses (17.8%) emphasized a scientific approach to the
      evaluation of CAM effectiveness. CONCLUSION: A wide variety of topics are being
      taught in U.S. medical schools under the umbrella of CAM. For the most part, the
      instruction appears to be founded on the assumption that unconventional therapies
      are effective, but little scientific evidence is offered. This approach is
      questionable, especially since mainstream medicine owes much of its success to a
      foundation of established scientific principles.

PMID- 12228086
TI  - Gold Foundation essay. The clinical experience that taught me the most.

PMID- 12228083
TI  - Randomized trial of an internet curriculum on herbs and other dietary supplements
      for health care professionals.
AB  - PURPOSE: Herbs and dietary supplements are widely used, and there is an urgent
      need to educate health professionals about their risks and benefits. The Internet
      provides an innovative way of educating busy health professionals. This study
      assessed the impact of an Internet-based curriculum on health professionals'
      knowledge, confidence, and clinical practices related to herbs and dietary
      supplements. METHOD: The study was a randomized crossover trial involving
      physicians, pharmacists, advanced practice nurses, and dietitians. Participants
      were invited by e-mail and randomly assigned to immediate intervention versus
      waiting-list groups (n = 537). The curriculum lasted ten weeks and consisted of
      20 case-based modules, each involving one multiple-choice or true-or-false
      question and its answer, links to reliable Internet sources of additional
      information, and a moderated listserv discussion group. Participants were
      surveyed about their knowledge, confidence, and communication related to herbs
      and dietary supplements on enrollment, after the immediate intervention group had
      completed the curriculum, and after the waiting-list group completed the
      curriculum. RESULTS: Baseline scores for knowledge, confidence, and communication
      were similar in the two groups. At the first follow-up, there was greater
      improvement in scores for all three areas in the immediate intervention group
      than in the waiting-list group (improvement for knowledge, 3.0 versus 1.4;
      confidence, 2.6 versus 0.6; communication, 0.21 versus -0.1, p <.01 for all
      comparisons). After all participants had received the curriculum, scores for both
      groups were significantly better than at baseline and similar to one another.
      CONCLUSION: Internet-based education about herbs and dietary supplements for
      diverse health professionals is feasible and results in significant and sustained
      improvements in knowledge, confidence, and communication practices.

PMID- 12228087
TI  - Using a productivity-based physician compensation program at an academic health
      center: a case study.
AB  - PURPOSE: With increased budget constraints, academic health centers (AHCs) have
      turned their focus on physician compensation. While many AHCs are concerned that
      compensation programs driven primarily by revenue generation will have a negative
      impact on their academic mission, little information is available to support
      this. The authors examined the effects on teaching and clinical productivity of
      an innovative compensation program for pediatrics primary care faculty at an AHC
      and related those effects to national standards for productivity. METHOD: A
      baseline productivity and compensation assessment was conducted for a group of 35
      academic general pediatricians. The data were compared with Medical Group
      Management Association (MGMA) figures for general pediatricians. A productivity
      based faculty compensation program using the work component of the relative-value
      unit (RVU) as the measure of productivity was designed and implemented.
      Productivity and compensation were measured after the first year of the program
      and compared with the baseline assessment. The numbers of hours precepting
      students and residents and the students' evaluations of their clinical
      experiences before and after implementation of the program were compared.
      RESULTS: The baseline assessment showed that over half of the faculty had
      productivity that fell below the MGMA 25th percentile, while the majority had
      compensation that exceeded this percentile. After implementation of the
      compensation program, 89% of the faculty increased their clinical productivity.
      The times faculty spent precepting and students' evaluations before and after
      program implementation were unchanged. CONCLUSIONS: Successful productivity-based
      physician compensation programs can be developed for AHCs.

PMID- 12228088
TI  - Assessing the reliability and validity of the mini-clinical evaluation exercise
      for internal medicine residency training.
AB  - PURPOSE: The mini-clinical evaluation exercise, or mini-CEX, assesses residents'
      history and physical examination skills. To date, no study has assessed the
      validity of the mini-CEX (mCEX) evaluation format. The authors' objective was to
      determine the reliability and validity of the mCEX evaluation format. METHOD:
      Twenty-three first-year residents at Wright-Patterson Medical Center in Dayton,
      Ohio, were included in the study (academic years 1996-97, 1997-98, and 1998-99).
      Validity of the instrument was determined by comparing mCEX scores with scores
      from corresponding sections of a modified version of the standard American Board
      of Internal Medicine's (ABIM's) monthly evaluation form (MEF) and the American
      College of Physicians-American Society of Internal Medicine In-Training
      Examination (ITE). All ABIM MEFs were used without exclusionary criteria,
      including ABIM MEFs from months where a corresponding mCEX evaluation was not
      performed. RESULTS: Each resident in the study had an average of seven mCEX
      evaluations and 12 ABIM MEFs. Of the 168 required mCEX evaluations, 162 were
      studied. Internal consistency reliability was .90. Statistically significant
      correlations were found for the following: mCEX history with ABIM history; mCEX
      physical exam with ABIM physical exam; mCEX clinical judgment with ABIM clinical
      judgment, medical care, medical knowledge, and the ITE; mCEX humanistic
      attributes with ABIM humanistic attributes, and mCEX overall clinical competence
      with ABIM overall clinical competence, medical care, medical knowledge, and the
      ITE. Analysis of variance comparing sequential mean mCEX scores yielded no
      significant difference. CONCLUSIONS: This study suggests that the mCEX is a
      feasible and reliable evaluation tool. The validity of the mCEX is supported by
      the strong correlations between mCEX scores and corresponding ABIM MEF scores as
      well as the ITE.

PMID- 12228089
TI  - Assessing third-year medical students' breast cancer screening skills.
AB  - PURPOSE: This study assesses the relationship between students' confidence and
      competency in breast screening practices, compares different measurement
      approaches to these competencies, and assesses the effect on clinical breast
      examination (CBE) performance of an additional training session with a
      standardized patient. METHOD: In the spring of 1998, 96 third-year medical
      students (47 men and 49 women) at the University of Massachusetts Medical School
      completed knowledge items on breast cancer epidemiology and on perceived
      confidence in their counseling and CBE skills. The students were also rated on
      their performances of counseling and CBE skills. RESULTS: Higher levels of
      confidence in mammography counseling skills and higher interview skills scores
      were associated with higher mammography counseling scores. Confidence levels in
      performing CBE, however, were not related to the actual performances of CBE.
      Students' knowledge of breast cancer was modestly related to their CBE scores.
      Finally, the students with one extra training session with a standardized patient
      performed significantly better on the CBE. CONCLUSIONS: It is important to
      directly measure students' breast cancer screening and physical examination
      skills because students' reported self-confidence for some skills might not
      accurately reflect their actual levels of performance. Additionally, while
      knowledge may be an important step to acquiring skills, knowledge may not be a
      good indicator of students' performances of risk assessment, counseling, or
      physical examination. Although confidence in counseling was related to counseling
      performance, the stability of this perception and how that translates into future
      cancer-control practices remain in question.

PMID- 12228090
TI  - Self-care in medical education: effectiveness of health-habits interventions for
      first-year medical students.
AB  - PURPOSE: To examine changes in health habits (sleep, alcohol, and exercise) and
      the effects of an educational intervention promoting self-care on the emotional
      and academic adjustment of first-year medical students. METHOD: Fifty-four
      medical students completed questionnaires that assessed various health habits,
      alcohol use, depression severity, and areas of life satisfaction at the beginning
      of the semester, at mid-term, and at finals. Approximately half of the students
      received written feedback or participated in an educational discussion group at
      mid-term. RESULTS: The students demonstrated significant changes in health
      habits, with increases in alcohol consumption and decreases in exercise and
      socialization. The changes in health habits were predictive of both emotional and
      academic adjustment, with students who decreased in positive health habits,
      particularly socialization, being more depressed at finals. The feedback and
      educational interventions influenced some sleep and exercise behaviors, but the
      groups did not differ in overall emotional or academic adjustment. CONCLUSIONS:
      First-year medical students show significant changes in health habits as they
      adjust to medical school. An educational intervention demonstrated promising
      effects in changing these patterns, but self-care needs to be further elaborated
      to address the specific challenges associated with acute adjustment as well as
      with long-term stressors.

PMID- 12228091
TI  - Depressed medical students' use of mental health services and barriers to use.
AB  - PURPOSE: Depression is an underrecognized yet common and treatable disorder among
      medical students. Little is known about the rate of mental health service use by
      depressed medical students. This study sought to determine the level of mental
      health service use by depressed medical students and their reported barriers to
      use. METHOD: In the spring of 1994, a one-time survey of 194 first- and second
      year medical students was conducted in the School of Medicine at the University
      of California, San Francisco. Outcome measures were self-reported use of
      counseling services, barriers to use, suicidal ideation, and depressive symptoms
      as measured by the 13-item Beck Depression Inventory (BDI). RESULTS: Twenty-four
      percent (n = 46) of the medical students were depressed by BDI criteria. Of the
      depressed students, only 22% (n = 10) were using mental health counseling
      services. The most frequently cited barriers to using these services were lack of
      time (48%), lack of confidentiality (37%), stigma associated with using mental
      health services (30%), cost (28%), fear of documentation on academic record
      (24%), and fear of unwanted intervention (26%). CONCLUSION: These data
      demonstrate that depression among medical students may be undertreated. Medical
      schools can assist depressed students by addressing issues such as the stigma of
      using mental health services, confidentiality, and documentation. Early treatment
      of impaired future caregivers may have far-reaching implications for the
      individual students, their colleagues, and their future patients.

PMID- 12228092
TI  - Primary care education: measuring instruction to improve quality.
AB  - The authors describe a validated instrument to measure instructional quality,
      using responses from first- and third-year medical students to assess ambulatory
      training sites.

PMID- 12228093
TI  - HEAL: an instructional design model applied to an online clerkship in family
      medicine.
AB  - OBJECTIVE: The potential of distance learning technology to deliver educational
      programs in which instruction and evaluation are of a consistent and high
      standard across multiple settings is hampered by a lack of instructional design
      models. In response, we developed the HEAL (Heuristic for Electronic Asynchronous
      Learning) model for designing online curricula. DESCRIPTION: HEAL is based on the
      theories that learning is facilitated by independent problem solving,
      investigation, and discovery (heuristics); collaboration between students fosters
      learning; and the proven educational cycle of practice, feedback, and reflection
      is integral to the interrelated domains of skill development and personal
      awareness.(1) The HEAL model is defined by synergistic online learning activities
      integrated with real patient care. It is applicable to all medical education
      levels. We applied this innovative design template to an online curriculum that
      augments our conventional six-week third-year clerkship. Our students, who were
      placed in distant family physician offices, needed more interaction and learning
      from peers and faculty. The three elements of HEAL, and implementation in the
      "online clerkship," are: (1) Didactic modules teach and illustrate concepts.
      Students study modules (HTML pages) on management of diabetes (DM), and complete
      five modules on evidence-based medicine (EBM). They do EBM literature searches
      reviewed online by peers, faculty, and librarians, who provide feedback. (2) A
      problem-based case discussion promotes application of concepts from modules
      (horizontal curricular integration). Students view streamed video of a patient
      with a history suggestive of diabetes, review her medical chart online, and
      suggest evidence-based management in an asynchronous discussion group. The case
      progresses weekly to mimic 12 months of continuity of care. (3) A collaborative
      journal activity explores the results of applying elements one and two to real
      patients (vertical integration). Additional elements advance reflection,
      professionalism, and medical humanism. Participation in the journal discussion
      group, stimulated by online readings, enhances self-awareness, informs
      psychosocial aspects of element 2, and promotes generalization of learning
      objectives to real patients. We use BlackBoard software. Students log in two to
      three times per week. Faculty who are trained in online moderation facilitate the
      threaded discussion groups and provide feedback. DISCUSSION: Students in
      alternating clerkship blocks complete the online clerkship. Their performance is
      compared with that of students who complete a face-to-face diabetes curriculum,
      but no curriculum on EBM or medical humanism. After nearly a year (105 students),
      compared with the non-online group, students completing the online clerkship
      demonstrated greater gains in reported EBM skills from preto post-clerkship,
      larger increases in mean score (from pre to post) on a medical-humanism aptitude
      scale, and higher scores on a post-clerkship diabetes management assessment (all
      comparisons p <.05). The online clerkship will become a permanent part of our
      clerkship and we have begun to use HEAL to design other online courses, including
      continuing education courses.

PMID- 12228094
TI  - Development of a Web-based question database for students' self-assessment.
AB  - OBJECTIVE: Computer-based testing (CBT) for the purpose of the national licensure
      examination has increased interest among medical students in this modality of
      testing. The advent of Web-based question-delivery systems for self-assessment
      and learning has made it possible for students to practice this technology and
      participate in self-directed learning. Test Pilot(TM) is a Web-based program that
      provides a fast and easy tool for the development and deployment of online
      testing. Our objectives for introducing the program were to (1) develop a large
      database of questions for students' practice and self-assessment; (2) include
      multimedia tools such as illustrations and short videos to enhance learning; (3)
      provide a feedback tool for clerkship and site directors regarding student
      performance; and (4) evaluate this tool in terms of students' frequency of use,
      students' satisfaction, and its potential effectiveness in enhancing learning.
      DESCRIPTION: The Obstetrics and Gynecology clerkship at the University of
      Michigan is held at four different sites. In the past, students have been
      provided with access to floppy disks that contain about 500 self-assessment
      questions. These questions have been reformatted, updated, and transferred to
      Test Pilot. Visual illustrations have been added to the questions along with more
      varied formats, including extended matching, fill-in, and essay questions. The
      questions are divided into ten-question quizzes. The students get immediate
      feedback after answering each question and a summary of performance at the end of
      each quiz. Security, access, and analysis are facilitated because the questions
      and responses are stored centrally. In addition, Test Pilot captures information
      regarding individual and collective students' performances. At the end of the
      rotation, students fill out a form evaluating the Test Pilot program and
      comparing it with the quiz disks. In addition, we are collecting data regarding
      the actual use of Test Pilot, which will be compared with the students' surveys
      and final exam scores. DISCUSSION: Test Pilot has many benefits, including access
      control, immediate feedback, automated scoring, interactive learning, and data
      analysis. The enhancement of material permitted by a Web-based system increases
      the depth and variety of the learning experience by adding perceptual dimensions.
      Test Pilot also provides the clerkship director with the capability to obtain
      improved measurements of student performance and captures the student's self
      learning and testing process. It can potentially identify weaknesses or
      inconsistencies across the different sites and recognize students who may need
      additional help early in the rotation. Over a one-year period, most students have
      switched from the quiz disks to Test Pilot. The students reported satisfaction
      with the Web-based format and found it user friendly. They especially liked the
      immediate feedback. The students have requested more questions and multimedia
      options be added. We plan to continue the development and assessment of this
      learning tool.

PMID- 12228095
TI  - MEDICOL: online learning in medicine and dentistry.
AB  - OBJECTIVE: MEDICOL (Medicine and Dentistry Integrated Curriculum Online) provides
      a variety of Web-based resources that act as important adjuncts to all the
      teaching components of the medical and dental undergraduate curriculum. It uses
      WebCT, a course-management system, to provide the following educational
      functions: (1) track students' progress and present course information such as
      time-tables, learning objectives, handout materials, images, references, course
      assignments, and evaluations; (2) promote student-to-student and student-to
      instructor interactions (through e-mail and bulletin boards); and (3) deliver
      self-directed learning components, including weekly self-assessment quizzes that
      provide immediate feedback and multimedia learning modules (clinical skills,
      radiology, evidence-based medicine, etc.). DESCRIPTION: The University of British
      Columbia Faculties of Medicine and Dentistry feature a problem-based learning
      (PBL) curriculum in which students access many of the same tools they will
      utilize in their professional practice. In the PBL curriculum, students must
      access the relevant clinical data and educational resources. A MEDICOL site has
      also been developed for medical students to use during their rural family
      practice, a four- to six-week experience in the summer after their second year.
      This site has been designed to be a supplemental learning environment for not
      only these students, but also for their physician preceptors. It is intended to
      foster communication among participants, bring new resources to the rural
      setting, and allow preceptors to develop their Internet skills with the help of
      students who are already familiar with the electronic environment. The MEDICOL
      sites enable the exchange of information about the learning issues between, as
      well as within, tutorial groups. MEDICOL also provides students with faculty
      reviewed resources that are listed online; multimedia presentations; and access
      to histology, radiology, and pathology images through an online image database.
      Each week, students have access to a new interactive and automatically graded
      self-assessment quiz for individual study. These quizzes test learning objectives
      from tutorial, lecture, and lab material for each week of the curriculum and are
      modeled after summative examinations held twice each year. Question authors
      provide immediately accessible quality feedback to students. A comprehensive quiz
      databank of approximately 1,500 questions has been attained. WebCT enables
      MEDICOL to deliver anonymous, online program-evaluation questionnaires during
      clinical clerkships (resulting in a 99% response rate after a few e-mail
      reminders), with easy and timely data collection and reporting methods. Summative
      assessments have also been delivered through MEDICOL. DISCUSSION: Use statistics
      indicate that over 90% of students regularly use the MEDICOL sites and have found
      them helpful. University of British Columbia medical school enrollment will
      increase because of collaborations with campuses and medical centers across the
      province. MEDICOL will likely play an increased role in distance learning by
      continuing to deliver the resources already described, as well as facilitating
      synchronous communications (e.g., PBL chat rooms) and teaching (e.g., video
      streamed lectures) to students located across the province.

PMID- 12228096
TI  - Working with interpreters: an interactive Web-based learning module.
AB  - OBJECTIVE: Medical students are presented with unique challenges when they care
      for patients with limited English proficiency. Students must learn a complex set
      of skills needed to care for patients across cultural and language barriers and
      to understand the impact of their own attitudes and beliefs about caring for
      these patients. We developed and piloted a multimedia interactive Web-based
      module aimed at teaching students effective strategies for working with
      interpreters and diverse patient populations, and at raising their awareness of
      important legal, ethical, and cultural issues. DESCRIPTION: First the learner
      completes a 37-multiple-choice-question (MCQ) pre-test that assesses attitudes,
      factual knowledge, and ability to analyze written clinical scenarios relevant to
      the module's content. Learners are then shown a series of professionally produced
      video vignettes, which reflect diverse patient populations, interpreters, and
      effectiveness of interpretation strategies (e.g., a Russian-speaking woman with
      chest pain whose daughter interprets, a medical student interpreting for a
      Chinese-speaking man using herbal medication, a Haitian woman told of an abnormal
      mammogram through a trained simultaneous interpreter). In each case, learners
      submit short answers to on-screen questions analyzing the effectiveness of the
      interpretation strategies demonstrated. Immediate feedback is given comparing
      student responses with those of experts. At any time during the module, the
      learners may view video commentary by legal, ethics, and cultural experts, or
      access a glossary and Web site links. Students conclude the module by again
      taking the MCQ test. A final screen compares their pre- and post-MCQ test
      responses and shows best answers, allowing them to assess their learning. The
      learners also complete a survey, providing personal cultural information and
      feedback on the module. DISCUSSION: All 160 first-year medical students completed
      the module and evaluated its effectiveness this year. On average, students
      improved by 20% on the MCQ post-test and 86% of the students were satisfied with
      the learning experience and acquired new knowledge. As a result of their
      participation in the module, students examined their own cultural and linguistic
      backgrounds and made the following comments: "I am interested in exploring the
      way my own culture and cultural biases could impact my working with patients from
      other cultures"; "This module has opened my eyes to the fears and concerns of
      immigrants who do not speak English." Therefore, this pilot of the module
      effectively imparted guidelines for, and raised awareness of, medical
      interpreting. The most common critique of the module was that as a result of
      technical difficulties, it was time-consuming. A more rigorous evaluation is
      planned for the next academic year. We are also working to enrich and enhance the
      module for more experienced clinicians (GME and CME). As a complementary
      educational tool, the Internet has the advantages of allowing students to work at
      their own paces, view engaging video clips, and participate in interactive
      learning with immediate feedback and self-assessment.

PMID- 12228097
TI  - Collaborative online learning: a new approach to distance CME.
AB  - OBJECTIVE: Continuing medical education (CME) has not taken advantage of the
      ability to communicate and collaborate online. Collaborative learning is an
      important learning principle, yet online CME programs are generally completed in
      a one-on-one relationship between the computer and the learner. This limits
      opportunities for reflective learning, and does not access the rich learning
      available from interacting with peers. We believe online CME will benefit from
      interaction between learners and from opportunities for reflection. DESCRIPTION:
      We implemented a prototype online course designed to improve the skills of
      general practitioners (GPs) in the care of patients with type 2 diabetes. The
      course design reflects adult learning principles but, uniquely, applies them to
      online learning. Currently, 20 GPs from England are enrolled, including one based
      in Bosnia, and one GP from New Zealand. The course uses BlackBoard(TM) software.
      Participants log in twice weekly for seven weeks to study one of seven
      interactive modules on diabetes from evidence-based sources. Modules provide for
      branched learning via links to additional resources. Subsequently, GPs engage in
      two online discussions, which are at the learner's convenience rather than
      requiring adherence to a set schedule. One discussion group is for reflection on
      the modules, with an assignment to discuss how the material is being applied
      clinically. Participants also respond to colleagues' postings each week. In a
      second discussion group, learners apply concepts from the modules to the
      collaborative management of a problem-based case of a patient with newly
      diagnosed diabetes. The patient is presented via an online medical chart and
      streaming videos. She returns each week of the course to mimic 18 months of care.
      Faculty facilitate the discussion groups and provide feedback. DISCUSSION: We are
      in the last week of the class and the participant feedback has been
      overwhelmingly positive. Many note how well the course design and timing match
      their learning styles and schedule constraints. A powerful feature has been our
      ability to identify additional educational needs, and quickly add corresponding
      content online. So far, participants have provided 340 postings, which include
      evidence of course effectiveness and documentation of application of course
      objectives and disease management strategies to change actual practice patterns.
      GPs report changing: screening practices for diabetic renal disease; prescribing
      of diabetic medications; screening protocols for diabetes; and organizing
      practice management systems to better track diabetic care. After diagnosing and
      managing a new diabetic patient during the course, one participant wrote: "It was
      fantastic to feel that I am offering an up-to-date evidence-based approach in
      something that I am deskilled in." This course is unique in online CME. It is
      international in scope, collaborative, asynchronous in delivery, flexible,
      responsive to learner needs in real time, and has yielded evidence of its
      effectiveness in changing the actual clinical practices of participants. It will
      next enroll GPs in Singapore and additional UK-based GPs. Additional CME courses
      will be developed using this method.

PMID- 12228098
TI  - A novel Web-based graduate medical education management system including ACGME
      compliance algorithms.
AB  - OBJECTIVE: Administration of graduate medical education programs has become more
      difficult as compliance with ACGME work guidelines has assumed increased
      importance. These guidelines have caused many changes in the resident work
      environment, including the emergence of complicated cross-cover arrangements.
      Many participating residents (each with his or her own individual scheduling
      requirements) usually generate these schedules. Accordingly, schedules are often
      not submitted in a timely fashion and they may not be in compliance with the
      ACGME guidelines for maximum on-call assignments and mandatory days off. Our
      objective was the establishment of a Web-based system that guides residents in
      creating on-call schedules that follow ACGME guidelines while still allowing
      maximum flexibility -- thus allowing each resident to maintain an internal locus
      of control. DESCRIPTION: A versatile and scalable system with password-protected
      user (resident) and administrator interfaces was created. An entire academic year
      is included, and past months and years are automatically archived. The residents
      log on within the first 15 days of the preceding month and choose their positions
      in a schedule template. They then make adjustments while receiving immediate
      summary feedback on compliance with ACGME guidelines. The schedule is
      electronically submitted to the educational administrator for final approval. If
      a cross-cover system is required, the program automatically generates an optimal
      schedule using both of the approved participating service schedules. The
      residents then have an additional five-day period to make adjustments in the
      cross-cover schedule while still receiving compliance feedback. The administrator
      again provides final approval electronically. The communication interface
      automatically pages or e-mails the residents when schedules are updated or
      approved. Since the information exists in a relational database, simple reporting
      tools are included to extract the information necessary to generate records for
      institutional GME management. DISCUSSION: Implementation of this program has been
      met with great enthusiasm from the institutional stakeholders. Specifically,
      residents have embraced the ability to directly control their schedules and have
      gained appreciation for the regulatory matrix in which they function.
      Institutional administrators have praised the improvement in compliance and the
      ease of documentation. We anticipate that the system will also meet with approval
      from reviewing regulatory bodies, as it generates and stores accurate information
      about the resident work environment. This program is robust and versatile enough
      to be modified for any GME training program in the country.

PMID- 12228099
TI  - Designing tailored Web-based instruction to improve practicing physicians'
      chlamydial screening rates.
AB  - OBJECTIVE: To design an individualized Web-based continuing medical education
      (CME) program to improve practicing physicians' chlamydial screening rates.
      DESCRIPTION: Often unrecognized and untreated, chlamydial infections in young
      women may cause pelvic inflammatory disease, infertility, and ectopic pregnancy
      and facilitate the acquisition of HIV. The National Committee for Quality
      Assurance in 2001 reported chlamydia screening rates to be 23.6% for 16-20-year
      olds and 18.3% for 21-26-year-olds. In a collaborative project an academic
      medical center and a large national managed care organization have developed four
      tailored Web-based modules for primary care physicians with the goal of improving
      rates of screening for chlamydia. Each module includes: (1) individual office
      chlamydial screening rates; (2) interactive cases with real-time comparison of
      answers with those of peers; (3) a toolbox of office support materials, including
      patient education materials and guideline summaries; and (4) real-time tailoring
      of the Web pages based on physicians' interactions with module. Readiness to
      change and barriers impeding change are assessed during interaction with the
      module and multiple pathways are created in real time for each physician.
      Physicians' perceptions of the prevalence of chlamydia in their patient
      populations and the rate of sexual activity among adolescent girls are also
      assessed. These variables have been correlated in other studies with low rates of
      chlamydial screening. Inaccurate perceptions of these variables are considered to
      constitute a precontemplative stage of change. Specific messages are designed to
      facilitate increased awareness of chlamydia prevalence, level of sexual activity,
      and the consequences of failure to screen. For physicians who are aware of the
      nature and scope of the problems related to chlamydia, messages are tailored to
      assist them in reducing barriers to screening. A randomized trial of a national
      sample of primary care physicians is being conducted to determine the
      effectiveness of this intervention in improving physicians' chlamydial screening
      rates in sexually active women 16-26 years of age. DISCUSSION: While the Internet
      offers an educational distribution system accessible to practicing physicians,
      most CME online programs are text-based and infrequently interactive or guideline
      based. It is unlikely that these programs have broad impact on physicians'
      practice patterns. Neither the broad capacities of Web technologies nor the
      evidence of effective methods for influencing physicians' practice patterns has
      influenced the design of most CME programs. The innovative course described above
      provides individual office feedback on performance, compares physicians'
      responses with those of their peers, gathers responses to determine physicians'
      readiness to change practices, and provides branching pathways "on-the-fly"
      individualized to these responses. The module format is easily adapted to other
      diseases, able to be linked in an automated fashion to administrative data files,
      and relatively low in cost to support.

PMID- 12228100
TI  - Implementing a systematic course/clerkship peer review process.
AB  - OBJECTIVE: A systematic course/clerkship peer-review process was developed to
      meet several objectives: improvement of quality of course/clerkship, enhancement
      of understanding of individual course and overall curricular content, improvement
      of communication and collaboration between basic science and clinical disciplines
      across campuses, provision of forum to address curricular concerns of students
      and faculty, facilitation of data collection for LCME reviews and the AAMC
      CurrMIT project; and monitoring curricular equivalency at multiple clinical
      sites. DESCRIPTION: Previously each course had carried out an internal review
      process. These reviews varied considerably in terms of the data collected and how
      those data were used for quality improvement. Data and outcomes of the internal
      reviews were seldom shared with colleagues, students, or administrators. This
      limited communication discouraged collaboration and led to disparity in
      curricular content between campuses. A collaborative effort between the medical
      school's Office of Medical Education (OME) and the Education Council, the faculty
      governance committee composed of faculty from each basic science and clinical
      department on each campus, has led to the development and implementation of a
      systematic course/clerkship peer-review process. Two standing committees of the
      Education Council oversee the systematic review process. One committee is charged
      with oversight of the first two years of the curriculum and a second committee
      with oversight of the third and fourth years. A two-tiered course/clerkship
      review process was designed with all courses undergoing a limited annual review.
      A comprehensive, "nuts and bolts" review for required courses was to occur every
      three years. The limited annual review was based on course evaluations completed
      by students, collected and summarized by the OME, and presented to the Education
      Council. The comprehensive review of a required course/clerkship occurred over a
      six-to-eight-month period. Course directors on each campus completed a
      questionnaire and submitted materials. To facilitate cross-discipline
      communication and synergy, a subcommittee composed of both basic science and
      clinical faculty, principally course directors, and at least one medical student
      who had completed the course at each campus reviewed submitted materials and had
      a series of meetings with the course directors, support personnel, and department
      chairs. Final review reports presented to the Education Council identify issues,
      concerns, and recommendations for action. To date 11 required courses have
      completed the comprehensive review process. Simple oversights, significant
      curricular disparity between campuses, and opportunities for multidisciplinary
      collaboration have been identified and addressed. Student-rated satisfaction has
      improved for those courses that have been reviewed. DISCUSSION: The systematic
      course/clerkship peer-review process has been a success, although there was
      initial resistance to "outside review." We have not yet completed one cycle of
      comprehensive course reviews but already faculty and administration have a better
      understanding of individual course and overall curriculum content. Faculty have
      developed working relationships and are sharing educational strategies across
      disciplines and campuses, and identifying innovative collaborations. The annual
      review process is now perceived to lack depth and is under reconsideration.

PMID- 12228101
TI  - An anticipatory quality improvement process for curricular reform.
AB  - OBJECTIVE: Over half of American medical schools are currently engaged in
      significant curricular reform. Traditionally, evaluation of the efficacy of
      educational changes has occurred well after the implementation of curricular
      reform, resulting in significant time elapsed before modification of goals and
      content can be accomplished. We were interested in establishing a process by
      which a new curriculum could be reviewed and refined before its actual
      introduction. DESCRIPTION: The University of California, San Francisco (UCSF)
      School of Medicine embarked upon a new curriculum for the class entering in
      September 2001. Two separate committees coordinated plans for curricular change.
      The Essential Core Steering Committee was responsible for the first two years of
      training, and the Integrated Clinical Steering Committee guided the development
      of the third-and fourth-year curriculum. Both groups operated under guidelines of
      curricular reform, established by the School's Committee on Curriculum and
      Educational Policy, that emphasized integration of basic, clinical, and social
      sciences; longitudinal inclusion of themes such as behavior, culture, and ethics;
      use of clinical cases in teaching; and inclusion of small-group and problem-based
      learning. In early 2001, the deans of education and curricular affairs appointed
      an ad hoc committee to examine the status of the first-year curriculum, which had
      been entirely reformulated into a series of new multidisciplinary block courses.
      This ad hoc committee was composed of students and clinical faculty members who
      had not been substantially involved in the detailed planning of the blocks. The
      charge to the committee was to critique the progress of individual courses, and
      the first year as a whole, in meeting the goals outlined above, and to make
      recommendations for improving the preparation of students for the clinical years.
      To accomplish these goals, the committee reviewed background planning documents;
      interviewed each course director using a standardized set of questions; and
      examined course schedules, cases, and detailed learning objectives for particular
      sessions. In July 2001, the committee reported back to the deans with specific
      recommendations for coordinating the block courses, and about the success in
      creating integration and the overall balance of topics students would learn.
      Specific recommendations included increasing the use of pediatric and geriatric
      cases across courses, creating a case database, developing explicit plans to
      relocate uncovered material in the four-year curriculum, and bolstering
      participation of clinical faculty during the first-year blocks. These
      recommendations were then presented to and endorsed by the Essential Core
      Steering Committee, which implemented an action plan prior to the September 2001
      start date. DISCUSSION: This proactive approach to quality improvement added an
      evaluation point before the new curriculum was actually unveiled. The
      anticipatory planning process substantially aided the interdisciplinary
      developmental process, increased input into the first-year curriculum by
      clerkship directors, and identified problems that would have otherwise become
      apparent after implementation. We believe this model adds value to the curriculum
      planning process.

PMID- 12228102
TI  - Implementing goals for non-cognitive outcomes within a basic science course.
AB  - OBJECTIVE: An essential principle of competency-based education (CBE) is use of
      observable outcomes with assessments as judgments of competence based on defined
      criteria. Faculty are accustomed to using learning objectives as the defining
      criteria for knowledge, assessing students using written exams. Faculty are less
      familiar with how the principles of CBE are applied to other competencies. We
      recently adopted school-wide goals and objectives, modeled after the ACGME
      Outcomes Project. The present objective was to give faculty first-hand experience
      in CBE within a basic science course, including both cognitive and non-cognitive
      outcomes. DESCRIPTION: The format for the learner-centered, first-year Cell and
      Molecular Biology course was previously described.(1) Course goals were that
      students: (1) gain an understanding of the principles and concepts of cell and
      molecular biology, (2) develop an appreciation for how these principles and
      concepts are important to medicine, (3) demonstrate an ability to think
      critically using these principles and concepts. Goal 1 was measured by written
      exams. We assumed goals 2 and 3 were met through small-group problem-solving
      sessions, and outcomes were not assessed. The revised 2001 course goals were to
      prepare students for medical knowledge and lifelong learning and communication
      and professionalism. The goals for medical knowledge and lifelong learning were
      to: (1) demonstrate ability to use principles and concepts of cell biology,
      molecular biology, and genetics to analyze medically relevant data, solve
      problems, make predictions, and determine a course of action; (2) effectively use
      information technology to search, evaluate, and critically review scientific
      evidence related to principles and concepts covered in the course; (3) use
      appropriate techniques to teach peers in a conference setting. The goals for
      communication and professionalism were to: (1) use appropriate skills and
      attitudes to collaborate effectively with peers and faculty to accomplish
      learning goals; (2) maintain a personal learning portfolio to develop habits of
      reflective learning, broaden understanding of content beyond recall, and enhance
      communication with faculty; (3) demonstrate personal integrity in meeting course
      requirements and in interactions with peers and faculty throughout the course.
      Goals for medical knowledge and lifelong learning were assessed by written exams
      and by separate tools utilizing four-point Likert scales (novice, advanced
      beginner, proficient, distinguished) with specific observable criteria for a
      written research paper and a group PowerPoint presentation. Faculty and student
      assessments generated a number that was combined with exam grades for a lettered
      competency grade. A 19-item, five-point Likert scale was used by students to self
      and peer-assess goals for communication and professionalism. Small-group faculty
      facilitators used the tool to give formative feedback midcourse, summative
      feedback at course conclusion, and competency grades. The tools may be viewed at:
      <www.meddean.luc.edu/lumen/meded/cellbio/index.htm>. DISCUSSION: Faculty achieved
      enhanced understanding of students, assisted by descriptive criteria, while
      suggesting improvements in forms. Better agreement on criteria definitions and
      consistency in form use is needed. Students developed understanding and improved
      communication/professionalism skills, based on repeated exposures to criteria and
      feedback. It remains to be seen whether the skills are used/developed in other
      courses. A majority of students did not use the learning portfolio as envisioned.
      Better design and implementation of school-wide rather than course-specific
      reflective portfolios may increase use and integrate learning in all courses with
      all six competencies.

PMID- 12228103
TI  - Changing an existing OSCE to a teaching tool: the making of a teaching OSCE.
AB  - OBJECTIVE: The teaching OSCE (objective structured clinical examination) was
      developed from existing OSCE materials to provide direct observation and feedback
      to students on their doctor-patient relationship skills, students' abilities to
      do a focused history and physical examination, and to familiarize students with
      this type of examination. DESCRIPTION: Existing OSCE cases were modified to ten
      minutes and to focus on case scenarios using standardized patients. Faculty
      facilitators were trained in giving feedback and oriented to the new OSCE format.
      Clerkship students are told in advance the general topics of the Teaching OSCE
      stations, so they can prepare. Students are divided in three groups of six to
      eight students and each group is assigned a faculty facilitator. Each student
      performs a ten-minute OSCE station and is observed directly by the faculty
      facilitator and the remaining students in the group using a video monitor. The
      faculty facilitator then leads a 12-minute feedback session on focused history
      taking skills, physical examination skills, and the doctor-patient relationship
      skills. Students selected at random by the faculty facilitator also give feedback
      to their peer. Teaching OSCEs take three hours and are held twice during the
      clerkship such that each student is actively observed twice and watches a total
      of ten to 14 additional interactions. Facilitators grade students on attendance,
      participation, and evidence of preparation. The actual interaction with the
      standardized patient is used entirely for formative purposes and is not graded.
      DISCUSSION: Our department has used OSCEs for six years to evaluate students at
      the end of the third-year family medicine clerkship. Even after continuous
      improvement, our OSCE did not meet higher standards of reliability and would need
      at least three hours of testing per student to meet those standards. The low
      number of students in the rotation and limited resources to increase the duration
      of the OSCE made it very difficult to construct a more reliable examination. At
      the same time, both faculty and students wanted more direct observation and
      feedback on performance with clinical scenarios. Using existing OSCE resources to
      change the OSCE to a teaching tool proved to be an efficient use of teaching
      resources while increasing our educational impact. Students report that they
      appreciate the opportunity to have constructive discussions of their strengths
      and weaknesses in clinical encounters, observe a variety of doctor-patient
      interaction styles, and practice for future OSCE-type examinations. Faculty
      members enjoy this active teaching format and find the process of students giving
      feedback to their peers educationally useful. The teaching OSCE has been
      extremely well rated in the end-of-rotation evaluations and will be continued in
      future clerkships.

PMID- 12228104
TI  - Implementation of geriatric education into the first and second years of a
      baccalaureate-MD degree program.
AB  - OBJECTIVE: As the population ages with an increasing standard of good health,
      medical students must redefine their views on aging and their approaches to aging
      and medicine. Consequently, the UM-KC School of Medicine has introduced an
      innovative approach to geriatric education. The approach seeks to help students
      view aging as a multidimensional process, challenge stereotypes about aging,
      learn about factors in healthy aging, and explore medical conditions of older
      patients. DESCRIPTION: To fulfill these objectives, each first- and second-year
      medical student (n = 200) in a six-year BA-MD degree program is paired with a
      mentor on aging. The mentor is an older adult living independently and
      experiencing normal psychosocial issues of aging without major medical problems.
      Over two years, students converse with their mentors about aging, keep journals
      reflecting on their conversations, complete projects with their mentors, and
      write scholarly papers. Thus, students can experience aging through their mentor
      relationships, gain an appreciation of their mentors' lives, and sharpen
      communication skills. In small groups, students and a physician-facilitator
      discuss problem-solving exercises keyed to American Geriatrics Society
      competencies and participate in an empathic aging exercise. Students also attend
      lectures on the care of older women and primary prevention. DISCUSSION:
      Assessment of students' performances is ongoing. Mentors have rated their
      students positively for being interested in them, being good listeners, and being
      eager to learn. Facilitators have rated most students highly for small-group
      participation. Instructors have reviewed and commented on student journals that
      suggest students have changed their stereotypes about older adults and
      appreciated the uniqueness of their mentors' lives. A performance-based
      assessment of the students' abilities to elicit life histories from senior
      volunteers will be administered halfway into the second year, and the scholarly
      papers will be critiqued at the end of the second year. Program evaluation is
      also under way. A pre-test of knowledge and attitudes showed students had little
      knowledge of the aging process, held negative stereotypes of older people, and
      preferred to care for younger patients. After-measures will be administered at
      the close of the second year. Evaluating their experience, mentors have said
      their interactions with students were enjoyable and beneficial to both parties.
      Students, while initially hostile because the program shifted their focus from
      sickly to healthy older adults, have found the evolving bonds between them and
      their mentors to be a benefit of the program. They believe that the most
      important lessons learned involved seeing the vitality and courage of older
      adults and improving their communication skills. Nevertheless, students feel they
      need more training in leading conversations and conducting interviews. Structured
      communication training will be added as the program continues to be a required
      part of the curriculum. Students have also thought the problem-solving cases
      should be more medically focused. While cases in the second year will emphasize
      medical aspects of aging, the cases in the first year will continue to explore
      psychosocial issues. Finally, to highlight psychosocial issues of aging, a
      session will be added utilizing a panel of older adults to provide examples and
      insights and to answer questions.

PMID- 12228105
TI  - Assessment of an integrated curriculum in radiology.
AB  - OBJECTIVE: To describe an interdisciplinary team's experience using a six-stage
      curriculum-development model to assess an integrated curriculum in radiology.
      DESCRIPTION: In 1996 the University of Maryland School of Medicine implemented
      reforms of its undergraduate curriculum. A third-year required clerkship in
      radiology was eliminated, but an integrated curriculum was developed for first-
      and second-year students and for third-year students during their core clinical
      clerkships. A fourth-year elective was retained. In 2000 the school's Curriculum
      Coordinating Committee found that it lacked data regarding program performance or
      learner competencies in radiology since the reforms were implemented. The
      Committee designated an interdisciplinary team including a radiologist, an
      anatomist, and an internist with medical education expertise to conduct a rapid
      review of the adequacy of the curriculum as it is currently integrated. The team
      mapped the curriculum, identifying where radiology was taught, and analyzed each
      sub-curriculum according to a six-stage curriculum-development model. This method
      permitted nearly concurrent assessment of the national literature, local needs
      assessment, presence and adequacy of educational objectives and methods, adequacy
      of resources to support curriculum implementation, and the availability and
      adequacy of learner and program outcome measures. The team identified changes in
      the clinical classrooms that have been unanticipated four years earlier,
      including implementation of PACS systems for digital film storage and retrieval,
      rapid advances in clinical imaging capabilities, and diminished faculty teaching
      time due to increased clinical volumes. The team concluded its work in four
      months and issued a report recommending revisions to third-year curricula. The
      Curriculum Committee, the Dean's Office, and the Department of Radiology accepted
      the analysis and have dedicated personnel, technical, and financial resources to
      effect the recommended revisions, which include (1) revision of clinical
      clerkship objectives for competencies in radiology, (2) development of Web-based
      modules for self-directed learning, (3) faculty development to enhance teaching
      skills, and (4) competency-based assessment measures based on learning
      objectives. DISCUSSION: Schools and faculty are often faced with the need to
      develop and implement innovative curricula rapidly. Periodic assessments by
      oversight groups such as curriculum committees identify where additional
      information is required to assess the performances of learners and curricula in
      rapidly-changing clinical contexts. In this study a three-member team with
      focused expertise in radiology, anatomy, and medicine/medical education conducted
      a rapid in-depth review of an integrated radiology curriculum "hosted" by several
      departments. A curriculum-development model provided a template for analysis of
      needs, objectives, methods, resources, and assessment measures for all curricula,
      and guided the team's recommendations for targeted revision. Each team member
      brought expertise in some element of the integrated curriculum or in curriculum
      design. The team identified what integrated curricular elements had not been
      designed adequately, what could no longer be supported with current resources,
      and how curricular revisions could be assessed for adequacy.

PMID- 12228106
TI  - Senior mentor program: a geriatrics focused curriculum.
AB  - OBJECTIVE: To introduce medical students to a healthy elderly population and
      present the health care challenges in this population. DESCRIPTION: As medical
      education has begun to focus more on our aging population and their future health
      needs, the University of South Carolina School of Medicine has developed a senior
      mentor program. This program provides a longitudinal experience for undergraduate
      students with local elders. The program, currently in its second year, will
      provide multiple opportunities for students to follow their same senior mentors
      over a four-year period both in the home and in the clinical setting. In
      partnership with the division of geriatrics, healthy patients over 65 were
      recruited to serve as senior mentors. Students, mostly in pairs, were assigned
      either one senior mentor or a couple, whom they met for the first time at the
      beginning of the second semester of their first year. Using a multidisciplinary
      approach, modules have been developed so students can learn how their senior
      mentors function on a daily basis, thus assessing the whole person, their health,
      their medical needs, their life-styles, and their social and physical
      environments. During the first year, students meet with their senior mentors four
      times and complete modules that address the physiology of aging, medical history
      taking, mental status examination, and psychological issues involving growing
      old. The modules were designed to coordinate with other areas of the curriculum
      where these concepts are being taught so that the students have an opportunity to
      put them into practice. Students check their senior mentors' blood pressures and
      write up their findings and thoughts about aging during each visit. In the second
      year the students meet with their senior mentors six times. Modules include
      assessing the senior mentors' diets; developing a behavioral modification plan in
      the first semester; and performing an environmental safety check, physical
      examination, and medication evaluation. The modules are coordinated with the
      curriculum and involve student consultation with our nutritionist and
      pharmacists. As the students enter their third and fourth years they will be
      expected to continue to meet with their senior mentors, to discuss issues
      concerning death and dying and advance directives, and to accompany their mentors
      to a physician visit. DISCUSSION: The responses from students, senior mentors,
      and faculty have been overwhelmingly positive. Students have enjoyed the early
      clinical experience, senior mentors have enjoyed meeting and talking to the
      students, and the faculty are pleased with the ability to integrate classroom
      material into a clinical setting early in the curriculum. Difficulties have
      arisen as some of our senior mentors have become ill and in the coordination of
      schedules between senior mentors and students. The plan is to continue the
      program as a permanent part of the curriculum. The hope is that it will be seen
      as a model for increasing the focus on geriatrics and early clinical experiences
      in the curriculum.

PMID- 12228107
TI  - Teaching interdisciplinary geriatrics team care.
AB  - OBJECTIVES: Addressing the current fragmentation and lack of coordination of
      health care requires that health professionals be skilled and motivated towards
      interdisciplinary team care. The objectives of our program are to (1) enhance
      attitudes towards team health care and (2) improve group interaction skills among
      interdisciplinary health care learners. DESCRIPTION: We nested an educational
      intervention focusing on skills and attitudes in interdisciplinary team care
      within a one-month rotation in an interdisciplinary geriatrics clinic. One day
      each week, a morning is devoted to small-group seminars, and learners participate
      as members of an interdisciplinary geriatrics clinical team in the afternoon.
      Learners are from four disciplines and include an internal medicine resident, a
      nurse practitioner, a social worker, and pharmacy students. During the small
      group seminars, eight hours are spent focusing on team care through facilitated
      discussions with assigned readings that include (1) motivational information and
      personal stories regarding the fragmented nature of current health care and
      personal attitudes and experiences with team care (2 hours), (2) a review of
      selected effective group communication skills (e.g., querying another learner
      about reasoning behind a statement before responding with a counter-opinion) (one
      hour), (3) case studies with team care planning and debriefing on group process
      behaviors (four hours), and (4) exploration of the potential relevance of team
      care to learners' own career paths (1 hour). The remaining seminars are devoted
      to topics in clinical geriatrics and managed care, and to reviewing patient files
      for the afternoon clinic. In the interdisciplinary clinic, learners spend an
      additional 18 hours seeing patients with a team that includes faculty from each
      of the four disciplines. Patients are seen jointly, and care plans are developed
      and implemented collaboratively. The primary outcome measures are pre- and post
      rotation attitudes regarding interdisciplinary team care. Concurrent controls who
      do not participate in the program are also assessed. Additional measures include
      faculty observation of communication behaviors, review of written
      interdisciplinary care plans, and learner perceptions of the value of the
      rotation. After a one-year planning and pilot period, the educational program is
      now in its third month of operation. DISCUSSION: Previous team-care training
      programs for health professionals have demonstrated difficulty in fostering
      effective attitudes and skills. During the planning and pilot year, we identified
      barriers to success that included (1) negative baseline attitudes toward
      interdisciplinary team care, especially among medical residents, (2) unrecognized
      assumptions and behaviors by learners regarding authority and power relationships
      within the team, and (3) specific concerns by learners regarding the
      effectiveness and efficiency of health care teams. We hope to demonstrate success
      through a program that includes direct examination of learners' attitudes and
      their origins in a safe environment, immediate feedback regarding group
      behaviors, case-based learning, and direct role exposure to a well-functioning
      interdisciplinary team.

PMID- 12228108
TI  - Palliative care module within a required geriatrics clerkship: taking advantage
      of existing partnerships.
AB  - OBJECTIVE: LCME has recently required that all graduating medical students learn
      about end-of-life care. This program describes the design and integration into an
      existing geriatrics clerkship of a palliative care module that teaches the
      foundations of end-of-life and palliative care to medical students. DESCRIPTION:
      Faculty experts in geriatrics met during a series of weekly meetings in 1999 to
      design a mandatory four-week-long clinical clerkship in geriatrics. Since the
      palliative care program is based within the geriatrics department, faculty
      members with interest and expertise in both geriatrics and palliative care were
      invited to design a palliative care module that can be integrated into the
      clerkship. Since LCME does not specify details of what students must learn about
      end-of-life care, and our goal is to educate and prepare students for any chosen
      specialty, we wanted to design a basic core curriculum in palliative care that
      would be useful to any graduating student. After reviewing potential palliative
      care topics, and given limited curriculum time, we condensed the medical student
      core curriculum to the following sessions: (1) Systematic Pain Assessment
      Management, (2) Management of Distressing Symptoms, (3) Communicating Bad News,
      and (4) Advance Directives. We developed PowerPoint presentations, teaching case
      vignettes, and a set of reference articles, which can be distributed to students
      as well as to help faculty teachers prepare for the sessions. Teaching sessions
      occur in small groups, using case discussions and interactive lectures. Sessions
      3 and 4 are co-facilitated by palliative care physicians and ethicists, who use
      role-plays, reflections, and discussions to teach the topics. At the end of the
      clerkship, students practice these communication skills with videotaped
      standardized patient encounters, and debrief with faculty members about their
      performances and ways to improve their communication skills. DISCUSSION:
      Palliative care sessions are welcomed by the students, who traditionally have not
      received much teaching in this area. Even though students have learned about
      mechanisms regulating pain and other symptoms in the past, they have not learned
      to assess or treat symptoms in a systematic way. Students often have good
      questions about the decision-making, legal, and ethical issues that emerge for
      patients near the end of life. Thus, co-facilitation of physicians with ethicists
      presents both the practical clinical and the theoretical perspectives, and
      provides a good model for team teaching. In terms of teaching style, students are
      more involved and participatory when teachers use case vignettes as compared with
      slide presentations, even if they are case-based. When using role-plays to teach
      students how to communicate bad news, we found that students need to feel safe in
      that environment, need to know they can call for time out when necessary, and
      want to have seen one done before they are asked to do one.

PMID- 12228109
TI  - A model of community-based interdisciplinary team training in the care of the
      frail elderly.
AB  - OBJECTIVE: It is widely recognized that interdisciplinary team care is essential
      for effective management of complex patients such as the frail elderly.
      Physicians need to understand the operational mechanisms that drive the team care
      model. While such concepts should be an integral part of medical education,
      teaching such a model of care that demonstrates effective provider communication,
      coordination of multiple services, and the provision of cost-effective health
      care can be difficult. The Program of All-inclusive Care of the Elderly (PACE) is
      a well-established, high-quality program that has been replicated nationally and
      can serve as an effective teaching model. Achieving the goals of the PACE program
      requires strong team leadership and communication, clear patient-oriented goal
      definition, an understanding and appreciation of roles among various disciplines,
      skillful negotiation, and shared responsibility for the patient. The PACE model
      offers medical and family practice residents a non-traditional clinical setting
      with educational opportunities not available in most hospital or ambulatory
      settings. DESCRIPTION: For several years the Fallon Healthcare System Elder
      Service Plan (ESP), one of 25 national PACE programs, has provided an educational
      setting for medical and family practice residents as a component of their
      clinical rotations in geriatrics. This training experience has been expanded to
      include additional residents in on-site interactive seminars that focus on
      effective communication using an interdisciplinary team approach to care. The ESP
      program provides comprehensive medical and social services to a frail, non
      institutionalized nursing-home-eligible population. The aim of the program is to
      preserve the health and independence of its participants for as long as possible.
      The ESP team consists of physicians, nurse practitioners, nurses, nurse's aides,
      home health workers, social workers, therapists, nutritionists, and pharmacists.
      The seminar includes a slide and video presentation led by members of the ESP
      team using selected scenarios that portray both effective and poor team dynamics
      and communication. Definitions of a team, the process of establishing patient-
      and family-oriented goals, interdisciplinary role appreciation and
      responsibility, and the basics of financing a comprehensive health care delivery
      system for the frail elderly are discussed. Approximately half of each session is
      devoted to interactive discussion and critiquing of the scenarios by the
      residents and faculty, which is derived from the ESP team. DISCUSSION: For most
      of the medical and family practice residents, this experience represents their
      first exposures to this model of coordinated team care for the elderly.
      Preliminary evaluation results indicate that residents have generally been
      unaware of the services available to the elderly and of the opportunities for
      coordinated care using the expertise of multiple disciplines. There is a lack of
      knowledge of key non-physician professional roles. The expanded use of PACE
      models as training sites could be beneficial in preparing future health care
      professionals for interdisciplinary team care of the growing numbers of frail
      elderly.

PMID- 12228110
TI  - A Web-based geriatrics portfolio to document medical students' learning outcomes.
AB  - OBJECTIVE: The University of Michigan Medical School is integrating into its
      curriculum the attitudes, knowledge, and skills that pertain to the care of older
      individuals using a defined set of core learning outcomes encompassing all four
      years. Students will demonstrate proficiency in these outcomes as a graduation
      requirement. We have developed an individualized, interactive, Web-based
      geriatrics portfolio to track the acquisition and mastery of these outcomes for
      students. DESCRIPTION: The required learning outcomes in geriatrics are presented
      to first-year students in their geriatrics portfolio Web page. The outcomes have
      been adapted from the recommendations published by the American Geriatrics
      Society's Education Committee.(1) The portfolio cross-references learning
      outcomes to specific activities in the curriculum. The activities include content
      given in lectures, multidisciplinary case discussions, standardized patient
      instructor (SPI) experiences involving older patients, and specific types of
      patient encounters during the clinical years. The portfolio allows documentation
      of completion dates of specific activities and the evaluations the student
      received. Certain activities such as the SPI experiences will include hyperlinks
      to their descriptions and the information that should be reviewed prior to each
      activity. The portfolio is integrated with existing administrative databases.
      Data entry occurs through links (e.g., exam scores), uploading comment forms from
      the SPI, and direct student input. One novel example of student input is the
      ability to upload information concerning encounters with older patients that
      students are recording in personal data assistant templates such that this
      information maps directly to the appropriate learning outcomes in their
      portfolios. The portfolio is designed to encourage students to take
      responsibility for their geriatrics education. Several types of evaluation data
      are provided, some that are specific to an activity (e.g., SPI feedback) and
      others that provide global assessments of learning outcomes (e.g., attitude
      surveys). The Web page can be displayed by the list of outcomes (categorized by
      attitudes, knowledge, and skills), by medical school year, and by date of
      completion. In this way, students can see at a glance how they are performing and
      whether they are up-to-date with completing the required outcomes. DISCUSSION:
      The geriatrics portfolio serves to identify and highlight geriatrics-related
      content across the four years. Its interactive features make it much more dynamic
      than a written transcript. Requiring proficiency in learning outcomes related to
      geriatrics for graduation will clearly convey to students that this information
      is critically important in their training to become physicians. The
      individualized evaluation summaries will prove useful to the student because self
      directed learning opportunities can be targeted to address weak areas. Evaluation
      of performances will also aid program directors to appropriately modify the
      curriculum to address any deficiencies. This innovative Web-based approach to
      capture learning outcomes that are dispersed throughout a four-year curriculum
      may also find application in similar curricula (e.g., women's health and end-of
      life care).

PMID- 12228111
TI  - An unfolding case with a linked OSCE: a curriculum in inpatient geriatric
      medicine.
AB  - OBJECTIVE: This study sought to design, implement, and evaluate a unique
      educational curriculum in inpatient geriatrics for internal medicine housestaff.
      DESCRIPTION: Traditionally the didactic curriculum on an inpatient geriatrics
      unit varies according to the attending faculty on service, the types of patients
      admitted, and preferences of the housestaff and students-in-training. However, a
      more structured educational curriculum would allow for comprehensive attention
      to, and a detailed exploration of, the principles of geriatric care necessary to
      effectively treat all hospitalized older adults. We have developed a unique
      curriculum using an unfolding case that is followed by an OSCE, which assesses
      the knowledge and skills gained by the learners. An unfolding case is one that
      evolves over time and is unpredictable to the learners when they begin
      participating in the curriculum. It is well suited to postgraduate training and
      assessment since the learner must develop a differential diagnosis, discuss
      possible work-ups, and use the work-ups' results to reassess the case as it
      unfolds. Our scripted case, administered by a geriatrics fellow rotating on the
      unit, follows an ambulatory geriatric patient from her admission throughout her
      treatment and until the end of her stay. It culminates in a decision-making
      session about her functional ability and hence her discharge plans. Moreover,
      several topics relevant to inpatient geriatrics, including dementia, delirium,
      falls, urinary incontinence, wound care, and depression, are covered in three one
      hour sessions. Written examinations or pre- and post-testing after an
      intervention are better suited to the early years of medical training but provide
      poor measures of curriculum mastery and clinical competency. Alternatively, our
      OSCE approach uses "stations" and "interstations" that provide a structured and
      timed opportunity to test these skills and assess specific areas of knowledge. We
      have designed a five-station, five-interstation OSCE that is conducted one week
      after the unfolding case-based conferences have ended. Learners are evaluated by
      attending physicians and given immediate feedback after each station and
      interstation. DISCUSSION: This newly developed project has been implemented as a
      standardized curriculum on our inpatient geriatrics unit since September 2001.
      Thus far, it has been extremely well received by housestaff because of real-time
      assessment and review of the materials covered during the month. In addition,
      this progressive approach has provided an excellent forum for geriatrics fellows
      to develop teaching skills. Attending physicians have shown their support,
      finding the content to be appropriate and relevant to inpatient geriatrics.
      Finally, this didactic approach will be continued on our unit and a modified
      version is being developed and piloted for other unit staff.

PMID- 12228112
TI  - An online discussion for medical faculty: an experiment that failed.
AB  - OBJECTIVE: Although online discussion groups are being used with increasing
      frequency in undergraduate and postgraduate education, their usefulness in
      faculty development has not been explored. The goal of this innovation was to
      offer an online discussion group following a faculty development workshop in
      order to reinforce workshop concepts and to allow participants to seek advice
      related to specific teaching and learning problems. We also wanted to assess the
      benefits of this educational tool. DESCRIPTION: We originally wanted to implement
      an online discussion group following a one-day workshop "The "Problem" Resident:
      Whose Problem Is It?" However, once this proposal was presented to our academic
      administrators, they asked us not to implement the discussion group because of
      concerns related to confidentiality and due process. They were worried that an
      online discussion might replace the faculty's evaluation and promotion
      guidelines, that teachers might no longer go to the "right" person to discuss a
      problem, and that we would give teachers a false sense of security. To respect
      these concerns, we changed the discussion topic and decided to implement an
      online discussion following a workshop "Promoting Interaction in Small-group
      Teaching." We chose this venue because it was less "emotionally charged" and
      because online discussions are seen as a potential adjunct to small-group
      teaching. We introduced the idea of a facilitated WebCT group discussion at the
      end of the workshop, and gave faculty members clear instructions on how to access
      the discussion group. Most of the workshop participants liked the idea of a
      follow-up to the workshop, but they preferred an e-mail listserv. We therefore
      decided to offer the WebCT discussion group to half of the participants, and an e
      mail listserv to the others. To initiate the discussion, we posted several issues
      for both groups, and we awaited the participants' responses. To our surprise,
      only two individuals (8%) responded on the e-mail listserv, after several
      attempts to stimulate discussion. DISCUSSION: In looking back at our "medical
      experiment" we were disappointed that our efforts to facilitate an online
      discussion following a faculty development workshop were not successful. However,
      based on personal reflections and conversations with a number of the workshop
      participants, we feel that some important lessons were learned. Time and
      competing demands clearly pose a major barrier. In addition, the "perceived need"
      of the initiative is critical. Our faculty members did not see the need for
      discussing interactive small-group teaching techniques online. Faculty members'
      comfort with technology must also be considered. Many of our teachers were not
      familiar with the potential uses of online learning. Moving faculty development
      beyond workshops also remains a challenge. With these lessons in mind, we plan to
      initiate another online discussion with faculty members, based on a need that
      they have defined around a topic that they have identified as critical to their
      own development as faculty members. We continue to believe that follow-up
      activities are essential in faculty development and that we need to further
      assess the potential value of this educational method.

PMID- 12228113
TI  - "Short stops": peer support of scholarly activity.
AB  - OBJECTIVES: Clinical and administrative responsibilities limit time for faculty
      to pursue scholarly activities. Scholarly work is, for most, difficult to
      accomplish in isolation. Yet organized opportunities for faculty interaction
      toward this goal are often lacking. To support one another in scholarly pursuits,
      three faculty members met in small groups every four to six weeks for about an
      hour. These "short stops" within hectic clinical and teaching schedules were
      brief, at intervals long enough to accomplish individual work, feasible in most
      faculty schedules, and based on the expectation that participants would prepare
      for the sessions and ask for specific input from the other participants.
      DESCRIPTION: Involvement as a fellow in the Ambulatory Pediatrics Association's
      Faculty Development Scholars Program illustrated the benefit of peer support and
      encouragement in embarking upon and making a commitment to clinical and
      educational research. In an effort to create such an environment, the author
      invited two pediatrics faculty members involved in student and resident education
      to meet every four to six weeks for about an hour with several goals in mind: (1)
      to define research questions based on clinical and educational work, (2) to
      brainstorm solutions for research barriers, (3) to interpret already-collected
      data, (4) to help each other meet deadlines, (5) to read and edit each other's
      work, and (6) to provide encouragement to fit this work into short stretches of
      time in busy schedules. Participants came to meetings prepared to present
      specific aspects of their work and to ask for specific input. Each meeting ended
      with the participants' setting personal goals for the next meeting. Frequent
      communication by e-mail and phone between meetings maintained the momentum. This
      continuity optimized the benefit of the short meetings. DISCUSSION: Within a year
      of implementing "short stops," there was an increase in new projects, submissions
      of abstracts to national meetings, presentations at national meetings, and
      submissions to journals. Although it cannot be shown that this was a direct
      result of "short stops," the three participants believe they are related. It
      appears that this format is optimal to promote active participation, sustain
      interest, and make use of mutual expectations to keep work on target. An
      unanticipated, but probably related, change was an increase in mentoring of
      residents' research projects by the program participants. As a result of our
      belief that the "short stops" method was successful in our small group, we went
      on to apply it in our 12-member division of general pediatrics. Twice-monthly
      breakfast or lunchtime meetings led by the author and another faculty member
      allow interested division members to attend depending on availability. Although
      this new process is in its early stages, half of the division members have
      already attended meetings. Just two months after starting the new group, each
      faculty participant has made a commitment to a next step toward a completed
      scholarly project.

PMID- 12228114
TI  - Recognizing clinical faculty's contributions in education.
AB  - OBJECTIVE: A faculty productivity profile system was designed to recognize
      faculty's contributions to administrative, educational, and research activities.
      It has long been recognized that clinical faculty receive little recognition or
      compensation for their efforts in education. Our surgery department previously
      had in place a recognition program for research achievements, but not for
      educational contributions. The new system was designed to recognize and reward
      all aspects of faculty contributions, including education. DESCRIPTION: The
      faculty productivity profile is a simple Excel document sent to each faculty
      member once a year. We piloted the program for the first time in 2001,
      recognizing faculty's contributions for the previous year. The pilot began with
      the formation of a committee whose first function was to identify all possible
      opportunities for faculty to participate as educators at our institution. This
      included giving lectures, participating in faculty development programs, serving
      as mentors, interviewing student or resident candidates, serving in
      administrative educational roles (e.g., clerkship or residency director), giving
      oral exams, or attending conferences and journal club. The committee then
      developed a point scale assigning each activity or contribution a value on a
      scale of 0-25. Each activity was then listed on the Excel form. Faculty were to
      fill in the number of times each activity was performed and this was multiplied
      by the points to obtain a weighted value. Point values for conferences were
      determined by percentage of conferences attended for a year (i.e., for grand
      rounds, those attending 0-49%, 50-75%, 75-90%, and more than 90% received 0, 20,
      40, and 60 points, respectively). Points were also assigned for teaching awards
      and high scores on student and resident evaluations. After approval by the
      committee and the department chairman, the form was presented at a faculty
      meeting. Each faculty member then received a floppy disk with the form and was
      asked to complete the form and attach a supporting copy of his or her CV. The
      form required only input of numbers or a "yes" or "no." After submission, the
      clerkship coordinator input additional data from a database of conference
      attendance and student evaluations. Points were then calculated for each faculty
      member based upon his or her contributions and each activity's weighted value. A
      dinner was held to recognize outstanding faculty contributions. All faculty
      completing the form were invited and recognized and those with outstanding
      contributions received awards. DISCUSSION: Teaching medical students and
      residents is a rewarding experience; however, it requires significant time and
      effort. Faculty who feel their contributions are unrecognized may be more likely
      to burn out and less likely to continue contributing. We believe it is worthwhile
      to recognize faculty contributions in all areas, including education. Our pilot
      program had excellent participation due to the ease of using the form. We believe
      it has improved faculty morale and willingness to participate. We are continuing
      the program and plan to evaluate its impact on encouraging continued
      participation in teaching.

PMID- 12228115
TI  - Microteaching and standardized students support faculty development for clinical
      teaching.
AB  - OBJECTIVE: If faculty development programs are to have impact, we believe they
      should be made up of several self-reinforcing workshops that provide
      opportunities for behavior review, practice, reflection, and reinforcement within
      a context of interdisciplinary perspectives. A program was developed that
      supports these four activities and includes clinical faculty from medicine,
      dentistry, nursing, and pharmacy. DESCRIPTION: At the University of Illinois at
      Chicago we have focused our efforts to improve clinical teaching through a
      program of two parallel courses. One course focuses on the "one-minute teacher"
      approach to clinical teaching. We call this course "Teaching-on-the-Fly,"
      reflecting what many of our faculty attendees have suggested they do. The second
      course is "Feedback Strategies." The two courses are identical in format, which
      is a series of three three-to-four-hour small-group workshops of not more than
      eight participants. The first two workshops in each series are titled "Teaching
      on-the-Fly I and II" and "Feedback Strategies I and II," respectively. Workshop I
      is separated from Workshop II by two weeks. During this hiatus faculty are urged
      to practice the skills learned and to reflect on what worked and what did not
      work in Workshop I. Six months following both series' Workshop II, "Advanced
      Teaching-on-the-Fly" and "Advanced Feedback Strategies" workshops are held. Each
      workshop begins with videotaping of two separate teaching encounters in which
      each participant interacts with standardized students. Standardized student and
      clinical faculty interactions are meant to mimic typical teaching and feedback
      situations. Teaching encounters are limited to five minutes, maximizing the
      similarity to the stress and frenetic quality of many of today's clinical
      settings. In Workshop II and in the advanced workshops the standardized students
      offer one positive comment to the faculty immediately following their encounter.
      Students are taught how to give this feedback. Immediately after videotaping,
      faculty adjourn to a small-group discussion. Workshops consist of reflective
      discussions during the review of each participant's videotape, brief lectures,
      and responsive comments and instruction by the workshop leaders. Participants are
      asked to reflect on each workshop and to bring examples of problems and
      opportunities gained to succeeding workshops in the series. DISCUSSION: Several
      theories support these clinical teaching workshops. (1) Outcomes research in
      continuing medical education suggests the need for ongoing reinforcement, which
      we do structurally through the three-session model. (2) We use a classical
      microteaching approach to develop insight and self-awareness. Each videotaped
      encounter is reviewed, stopped at key points, and discussed by the entire group.
      These discussions commonly open up after the workshop leaders ask questions such
      as, "What were you thinking there?" or "What were you trying to do?" or "What
      would you ask next?" (3) We emphasize the importance of knowing-in-action and the
      related reflection that guides action in practice. (4) The quality of the
      workshops is enhanced using standardized students, whom we carefully train and
      use repeatedly. At least two students have worked with us from their first years
      through their final clinical years. We are currently examining the program's
      impact through videotape review.

PMID- 12228116
TI  - Alosetron for irritable bowel syndrome.

PMID- 12228117
TI  - When medical students go off the rails.

PMID- 12228118
TI  - Acute compartment syndrome of the leg.

PMID- 12228119
TI  - Patient education programmes for adults with rheumatoid arthritis.

PMID- 12228120
TI  - Placebos and standardising new surgical techniques.

PMID- 12228122
TI  - Doctors fail to see the joke.

PMID- 12228121
TI  - FDA advisers warn of more deaths if drug is relaunched.

PMID- 12228124
TI  - Patent laws are keeping poor countries in poverty.

PMID- 12228125
TI  - Mental health campaigners cancel march because of fears of backlash.

PMID- 12228128
TI  - US medical schools should consider race in admitting students.

PMID- 12228130
TI  - Organ transplants and blood transfusions may transmit West Nile virus.

PMID- 12228131
TI  - Incidence of cancer among Nordic airline pilots over five decades: occupational
      cohort study.
AB  - OBJECTIVE: To assess the incidence of cancer among male airline pilots in the
      Nordic countries, with special reference to risk related to cosmic radiation.
      DESIGN: Retrospective cohort study, with follow up of cancer incidence through
      the national cancer registries. SETTING: Denmark, Finland, Iceland, Norway, and
      Sweden. PARTICIPANTS: 10 032 male airline pilots, with an average follow up of 17
      years. MAIN OUTCOME MEASURES: Standardised incidence ratios, with expected
      numbers based on national cancer incidence rates; dose-response analysis using
      Poisson regression. RESULTS: 466 cases of cancer were diagnosed compared with 456
      expected. The only significantly increased standardised incidence ratios were for
      skin cancer: melanoma 2.3 (95% confidence interval 1.7 to 3.0), non-melanoma 2.1
      (1.7 to 2.8), basal cell carcinoma 2.5 (1.9 to 3.2). The relative risk of skin
      cancers increased with the estimated radiation dose. The relative risk of
      prostate cancer increased with increasing number of flight hours in long distance
      aircraft. CONCLUSIONS: This study does not indicate a marked increase in cancer
      risk attributable to cosmic radiation, although some influence of cosmic
      radiation on skin cancer cannot be entirely excluded. The suggestion of an
      association between number of long distance flights (possibly related to
      circadian hormonal disturbances) and prostate cancer needs to be confirmed.

PMID- 12228132
TI  - Observational study of vaccine efficacy 14 years after trial of hepatitis B
      vaccination in Gambian children.
AB  - OBJECTIVE: To determine the duration of protection from hepatitis B vaccine given
      in infancy and early childhood. DESIGN: Cross sectional serological study of
      hepatitis B virus infection in children of various ages 14 years after the start
      of a trial of vaccination regimens. SETTING: Two villages in the Gambia.
      PARTICIPANTS: Children and adolescents given hepatitis B vaccine in infancy or
      early childhood: 232 were aged 1-5 years, 225 aged 5-9 years, 220 aged 10-14
      years, and 175 aged 15-19 years. MAIN OUTCOME MEASURES: Vaccine efficacy against
      infection and against chronic infection in the different age groups. RESULTS:
      Vaccine efficacy against chronic carriage of hepatitis B virus was 94% (95%
      confidence interval 89% to 97%), which did not vary significantly between the age
      groups. Efficacy against infection was 80% (76% to 84%). This was significantly
      lower in the oldest age group (65%, 56 to 73). Of the uninfected participants in
      this age group, 36% had no detectable hepatitis B virus surface antibody. Time
      since vaccination and a low peak antibody response were the most powerful risk
      factors for breakthrough infection (P<0.001 in each case). Low peak antibody
      response was also a risk factor for chronic carriage (odds ratio 95, 19 to 466).
      CONCLUSIONS: Children vaccinated in infancy are at increased risk of hepatitis B
      virus infection in the late teens. The risk of chronic carriage after sexual
      exposure needs further assessment to determine if booster vaccines are necessary.

PMID- 12228133
TI  - Type specific persistence of high risk human papillomavirus (HPV) as indicator of
      high grade cervical squamous intraepithelial lesions in young women: population
      based prospective follow up study.
AB  - OBJECTIVES: To investigate the role of human papillomavirus (HPV) in the
      development of cervical neoplasia in women with no previous cervical cytological
      abnormalities; whether the presence of virus DNA predicts development of squamous
      intraepithelial lesion; and whether the risk of incident squamous intraepithelial
      lesions differs with repeated detection of the same HPV type versus repeated
      detection of different types. DESIGN: Population based prospective cohort study.
      SETTING: General population in Copenhagen, Denmark. PARTICIPANTS: 10 758 women
      aged 20-29 years followed up for development of cervical cytological
      abnormalities; 370 incident cases were detected (40 with atypical squamous cells
      of undetermined significance, 165 with low grade squamous intraepithelial
      lesions, 165 with high grade squamous intraepithelial lesions). MAIN OUTCOME
      MEASURES: RESULTS of cervical smear tests and cervical swabs at enrollment and at
      the second examination about two years later. RESULTS: Compared with women who
      were negative for human papillomavirus at enrollment, those with positive results
      had a significantly increased risk at follow up of having atypical cells (odds
      ratio 3.2, 95% confidence interval 1.3 to 7.9), low grade lesions (7.5, 4.8 to
      11.7), or high grade lesions (25.8, 15.3 to 43.6). Similarly, women who were
      positive for HPV at the second examination had a strongly increased risk of low
      (34.3, 17.6 to 67.0) and high grade lesions (60.7, 25.5 to 144.0). For high grade
      lesions the risk was strongly increased if the same virus type was present at
      both examinations (813.0, 168.2 to 3229.2). CONCLUSIONS: Infection with human
      papillomavirus precedes the development of low and high grade squamous
      intraepithelial lesions. For high grade lesions the risk is greatest in women
      positive for the same type of HPV on repeated testing.

PMID- 12228134
TI  - The mental health of UK Gulf war veterans: phase 2 of a two phase cohort study.
AB  - OBJECTIVES: To examine the prevalence of psychiatric disorders in veterans of the
      Gulf war with or without unexplained physical disability (a proxy measure of ill
      health) and in similarly disabled veterans who had not been deployed to the Gulf
      war (non-Gulf veterans). DESIGN: Two phase cohort study. SETTING: Current and ex
      service UK military personnel. PARTICIPANTS: Phase 1 consisted of three randomly
      selected samples of Gulf veterans, veterans of the 1992-7 Bosnia peacekeeping
      mission, and UK military personnel not deployed to the Gulf war (Era veterans)
      who had completed a postal health questionnaire. Phase 2 consisted of randomly
      selected subsamples from phase 1 of Gulf veterans who reported physical
      disability (n=111) or who did not report disability (n=98) and of Bosnia (n=54)
      and Era (n=79) veterans who reported physical disability. MAIN OUTCOME MEASURE:
      Psychiatric disorders assessed by the schedule for clinical assessment in
      neuropsychiatry and classified by the Diagnostic and Statistical Manual of Mental
      Disorders, fourth edition. RESULTS: Only 24% (n=27) of the disabled Gulf veterans
      had a formal psychiatric disorder (depression, anxiety, or alcohol related
      disorder). The prevalence of psychiatric disorders in non-disabled Gulf veterans
      was 12%. Disability and psychiatric disorders were weakly associated in the Gulf
      group when confounding was adjusted for (adjusted odds ratio 2.4, 99% confidence
      interval 0.8 to 7.2, P=0.04). The prevalence of psychiatric disorders was similar
      in disabled non-Gulf veterans and disabled Gulf veterans ( 19% v 24%; 1.3, 0.5 to
      3.4). All groups had rates for post-traumatic stress disorder of between 1% and
      3%. CONCLUSIONS: Most disabled Gulf veterans do not have a formal psychiatric
      disorder. Post-traumatic stress disorder is not higher in Gulf veterans than in
      other veterans. Psychiatric disorders do not fully explain self reported ill
      health in Gulf veterans; alternative explanations for persistent ill health in
      Gulf veterans are needed.

PMID- 12228135
TI  - Doctors' perceptions of drinking alcohol while on call: questionnaire survey.

PMID- 12228137
TI  - Vulvovaginal candidiasis.

PMID- 12228136
TI  - Doctors' perceptions of palliative care for heart failure: focus group study.
AB  - OBJECTIVES: To identify doctors' perceptions of the need for palliative care for
      heart failure and barriers to change. DESIGN: Qualitative study with focus
      groups. SETTING: North west England. PARTICIPANTS: General practitioners and
      consultants in cardiology, geriatrics, palliative care, and general medicine.
      RESULTS: Doctors supported the development of palliative care for patients with
      heart failure with the general practitioner as a central figure. They were
      reluctant to endorse expansion of specialist palliative care services. Barriers
      to developing approaches to palliative care in heart failure related to three
      main areas: the organisation of health care, the unpredictable course of heart
      failure, and the doctors' understanding of roles. The health system was thought
      to work against provision of holistic care, exacerbated by issues of professional
      rivalry and control. The priorities identified for the future were developing the
      role of the nurse, better community support for primary care, and enhanced
      communication between all the health professionals involved in the care of
      patients with heart failure. CONCLUSIONS: Greater consideration should be given
      to the care of patients dying with heart failure, clarifying the roles of doctors
      and nurses in different specialties, and reshaping the services provided for
      them. Many of the organisational and professional issues are not peculiar to
      patients dying with heart failure, and addressing such concerns as the lack of
      coordination and continuity in medical care would benefit all patients.

PMID- 12228138
TI  - Interpreting the evidence.

PMID- 12228139
TI  - Chest pain.

PMID- 12228140
TI  - Alosetron: a case study in regulatory capture, or a victory for patients' rights?

PMID- 12228141
TI  - NHS league tables are more spin than substance.

PMID- 12228142
TI  - Barriers to effective stroke care out of hours need to be broached.

PMID- 12228143
TI  - Cases of congenital rubella may be the tip of the iceberg.

PMID- 12228144
TI  - Aspects of MMR. Survey shows that some homoeopaths and chiropractors advise
      against MMR.

PMID- 12228145
TI  - Systematic review of cost effectiveness in telemedicine. Quality of cost
      effectiveness studies in systematic reviews is problematic.

PMID- 12228146
TI  - Brain death. Brain death is a recent invention.

PMID- 12228147
TI  - Staphylococci may indeed cause acute dental infections.

PMID- 12228148
TI  - Children are still seen but not heard.

PMID- 12228149
TI  - Recommendations from quality of life scales are not simple.

PMID- 12228150
TI  - Parents are an untapped resource in sex education.

PMID- 12228151
TI  - Mobile phone text messaging can help young people manage asthma.

PMID- 12228153
TI  - Imaging of the hand and wrist in RA.

PMID- 12228152
TI  - Treating human autoimmune disease by depleting B cells.

PMID- 12228154
TI  - Interleukin 17 synergises with tumour necrosis factor alpha to induce cartilage
      destruction in vitro.
AB  - BACKGROUND: Interleukin 17 (IL17) is produced by activated T cells and has been
      implicated in the development of bone lesions and cartilage degradation in
      rheumatoid arthritis (RA). OBJECTIVE: To determine whether IL17, alone or
      together with tumour necrosis factor alpha (TNFalpha), induces cartilage
      destruction in vitro. METHODS: Fetal mouse metatarsals stripped of endogenous
      osteoclast precursors were used to study the effect of IL17 on cartilage
      degradation independently of osteoclastic resorption. Cartilage destruction was
      analysed histologically by Alcian blue staining. RESULTS: IL17 alone, up to 100
      ng/ml, had no effect on the cartilage of fetal mouse metatarsals. IL17 (>/=0.1
      ng/ml), however, induced severe cartilage degradation when given together with
      TNFalpha (>/=1 ng/ml). The cytokine combination decreased Alcian blue staining, a
      marker of proteoglycans, throughout the metatarsals and induced loss of the
      proliferating and early hypertrophic chondrocyte zones. TNFalpha alone also
      decreased Alcian blue staining, but not as dramatically as the cytokine
      combination. In addition, it did not induce loss of chondrocyte zones. Treatment
      with inhibitors of matrix metalloproteinase (MMP) activity and nitric oxide
      synthesis showed that MMP activity played a part in cartilage degradation,
      whereas nitric oxide production did not. CONCLUSIONS: IL17, together with
      TNFalpha, induced cartilage degradation in fetal mouse metatarsals in vitro. IL17
      may, therefore, participate in the development of cartilage destruction
      associated with RA by enhancing the effects of TNFalpha and may provide a
      potential therapeutic target.

PMID- 12228155
TI  - Power Doppler sonography in the assessment of synovial tissue of the knee joint
      in rheumatoid arthritis: a preliminary experience.
AB  - OBJECTIVE: To investigate the intra-articular vascularisation of the synovial
      pannus in the knee of patients with rheumatoid arthritis (RA) with power Doppler
      ultrasonography (PDS) and an echo contrast agent and correlate the area under the
      time-intensity curves with the clinical findings and laboratory measures of
      disease activity. METHOD: Forty two patients with RA (31 women, 11 men) with
      history and signs of knee arthritis, classified according to a modified index of
      synovitis activity (active, moderately active, and inactive), were studied.
      Clinical and functional assessment (number of swollen joints, intensity of pain,
      general health-visual analogue scale, disability index-Health Assessment
      Questionnaire, Ritchie articular index) and a laboratory evaluation were made on
      all patients. Disease activity was evaluated using the disease activity score
      (DAS) and the chronic arthritis systemic index (CASI) for each patient. All
      patients were examined with conventional ultrasonography and PDS before injection
      of intravenous ultrasound contrast agent (Levovist). The quantitative estimation
      of the vascularisation of the synovial membrane was performed with time-intensity
      curves and calculation of the area under the curves. RESULTS: The mean (SD) value
      of the area underlying time-intensity curves was 216.2 (33.4) in patients with
      active synovitis, 186.8 (25.8) in patients with moderately active synovitis, and
      169.6 (20.6) in those with inactive synovitis. The mean value of the areas
      differed significantly between the patients with active and those with inactive
      synovitis (p<0.01). The mean value of the area under the curve of the entire
      group was weakly correlated with the number of swollen joints (p=0.038), but a
      strong correlation was found with composite indexes of disease activity such as
      the DAS (p=0.006) and CASI (p=0.01). No correlation was found with age, disease
      duration, and other laboratory and clinical variables. CONCLUSION: PDS may be a
      valuable tool to detect fractional vascular volume and to assist clinicians in
      distinguishing between inflammatory and non-inflammatory pannus. The transit of
      microbubbles of ultrasound contrast across a tissue can be used to estimate
      haemodynamic alterations and may have a role in assessing synovial activity and
      the therapeutic response to treatment of synovitis of the knee joint.

PMID- 12228157
TI  - Clinical outcome in 22 patients with rheumatoid arthritis treated with B
      lymphocyte depletion.
AB  - OBJECTIVES: To obtain evidence for dose response and to extend evidence of safety
      and efficacy for B lymphocyte depletion in rheumatoid arthritis. METHODS: Twenty
      two patients with rheumatoid arthritis received a total of 29 treatments with
      five different combinations of rituximab (RTX), cyclophosphamide (CP), and/or
      high dose prednisolone (PR) on an open basis as follows; cohort I: RTX 1400
      mg/m(2), CP 750x2+PR; cohort II: RTX 300-700 mg/m(2), -CP+/-PR); cohort III: RTX
      600-700 mg/m(2), CP 750x2+PR; cohort IV: RTX 1200 mg/m(2), CP 750x2-PR; cohort V:
      RTX 500 mg/m(2), CP 750x2+PR. American College of Rheumatology (ACR) criteria of
      improvement at six months were chosen as the primary outcome measure. Disease
      activity scores and total duration of improvement and of B cytopenia were also
      recorded. RESULTS: No major adverse events attributable to treatment were seen.
      ACR grades of improvement at six months were as follows: cohort I: ACR70x3,
      ACR50x2; cohort II: ACR20x1, ACR0x3; cohort III: ACR70x6, ACR50x2, ACR20x2;
      cohort IV: ACR70x2, ACR50x2, ACR20x1, ACR0x1; cohort V: ACR0x4. CONCLUSIONS: B
      lymphocyte depletion in rheumatoid arthritis has so far proved to be safe and
      associated with major improvement with protocols including RTX 600 mg/m(2) or
      more and CP, but not with more limited protocols. These observations provide an
      initial basis for the design of formal trials of B cell depletion and other B
      cell directed treatments, including a phase II controlled trial now in progress.

PMID- 12228159
TI  - Mortality in patients with rheumatoid arthritis treated actively from the time of
      diagnosis.
AB  - OBJECTIVES: To evaluate the mortality rates among patients with early rheumatoid
      arthritis (RA) treated actively according to the "sawtooth" strategy. METHODS:
      The study included 150 early, disease modifying antirheumatic drug (DMARD) naive
      patients with RA from two patient cohorts. The first cohort was assembled between
      1986 and 1989 (87 patients, aged 19-65 years at onset) and the second between
      1991 and 1993 (63 patients, aged 27-83 years at onset). The mean duration of
      symptoms at the time of diagnosis was 7.1 months (range 2-24). The clinical data
      and the use of DMARDs were systematically recorded. The causes of death were
      obtained from death certificates and medical records, if available. The data were
      collected up to 1 November 2000. RESULTS: During a follow up time of 7-14 years,
      24 patients died. The standardised mortality ratio was not increased (0.93 in the
      first cohort and 1.62 in the second cohort). Age adjusted mortality rates did not
      differ statistically significantly between the two patient cohorts. The causes of
      death included malignancy (8 patients); cardiovascular diseases (10); respiratory
      disease (4), including two patients with pneumonia; sepsis (one); and RA (one).
      High inflammatory activity, disease activity, and poor functional ability at
      study entry, and the presence of extra-articular features during the follow up
      were more common among the patients who had died. CONCLUSIONS: No statistically
      significant increase in mortality rates was seen in these actively treated early
      RA cohorts during the follow up. High disease activity at the onset and the
      development of extra-articular features seem to be associated with mortality.

PMID- 12228160
TI  - Prospective two year follow up study comparing novel and conventional imaging
      procedures in patients with arthritic finger joints.
AB  - OBJECTIVE: To carry out a prospective two year follow up study comparing
      conventional radiography, three-phase bone scintigraphy, ultrasonography (US),
      and three dimensional (3D) magnetic resonance imaging (MRI) with precontrast and
      dynamic postcontrast examination in detecting early arthritis. The aim of the
      follow up study was to monitor the course of erosions during treatment with
      disease modifying antirheumatic drugs by different modalities and to determine
      whether the radiographically occult changes like erosive bone lesions of the
      finger joints detected by MRI and US in the initial study would show up on
      conventional radiographs two years later. Additionally, to study the course of
      soft tissue lesions depicted in the initial study in comparison with the clinical
      findings. METHODS: The metacarpophalangeal, proximal interphalangeal, and distal
      interphalangeal joints (14 joints) of the clinically more severely affected hand
      (soft tissue swelling and joint tenderness) as determined in the initial study of
      49 patients with various forms of arthritis were examined twice. The patients had
      initially been divided into two groups. The follow up group I included 28
      subjects (392 joints) without radiographic signs of destructive arthritis (Larsen
      grades 0-1) of the investigated hand and wrist, and group II (control group)
      included 21 patients (294 joints) with radiographs showing erosions (Larsen grade
      2) of the investigated hand or wrist, or both, at the initial examination.
      RESULTS: (1) Radiography at the two year follow up detected only two erosions
      (two patients) in group I and 10 (nine patients) additional erosions in group II.
      Initial MRI had already detected both erosions in group I and seven (seven
      patients) of the 10 erosions in group II. Initial US had depicted one erosion in
      group I and four of the 10 erosions in group II. (2) In contrast with
      conventional radiography, 3D MRI and US demonstrated an increase in erosions in
      comparison with the initial investigation. (3) The abnormal findings detected by
      scintigraphy were decreased at the two year follow up. (4) Both groups showed a
      marked clinical improvement of synovitis and tenosynovitis, as also shown by MRI
      and US. (5) There was a striking discrepancy between the decrease in the soft
      tissue lesions as demonstrated by clinical findings, MRI, and US, and the
      significant increase in erosive bone lesions, which were primarily evident at MRI
      and US. CONCLUSIONS: Despite clinical improvement and a regression of
      inflammatory soft tissue lesions, erosive bone lesions were increased at the two
      year follow up, which were more pronounced with 3D MRI and less pronounced with
      US. The results of our study suggest that owing to the inadequate depiction of
      erosions and soft tissue lesions, conventional radiography alone has limitations
      in the intermediate term follow up of treatment. US has a high sensitivity for
      depicting inflammatory soft tissue lesions, but dynamic 3D MRI is more sensitive
      in differentiating minute erosions.

PMID- 12228161
TI  - Ultrasonography of entheseal insertions in the lower limb in spondyloarthropathy.
AB  - OBJECTIVE: To compare ultrasonography (US) with clinical examination in the
      detection of entheseal abnormality of the lower limb in patients with
      spondyloarthropathy (SpA). METHODS: 35 patients with SpA (ankylosing spondylitis
      27; psoriatic arthritis 7; reactive arthritis 1) underwent independent clinical
      and ultrasonographic examination of both lower limbs at five entheseal sites
      superior pole and inferior pole of patella, tibial tuberosity, Achilles tendon,
      and plantar aponeurosis. US was performed using an ATL (Advanced Technology
      Laboratories, Bothell, Washington, USA) high definition imaging 3000 machine with
      linear 7-4 MHz and compact linear 10-5 MHz probes to detect bursitis, structure
      thickness, bony erosion, and enthesophyte (bony spur). An enthesitis score was
      formulated from these US findings giving a possible maximum total score of 36.
      RESULTS: On clinical examination 75/348 (22%) entheseal sites were abnormal and
      on US examination 195/348 (56%) sites were abnormal. In 19 entheseal sites with
      bursitis on US, only five were detected by clinical examination. Compared with
      US, clinical examination had a low sensitivity (22.6%) and moderate specificity
      (79.7%) for the detection of enthesitis of the lower limbs. There was no
      significant correlation between the US score of enthesitis and acute phase
      parameters such as erythrocyte sedimentation rate (ESR) or C reactive protein
      (CRP). The intraobserver kappa value for analysis of all sites was 0.9.
      CONCLUSIONS: Most entheseal abnormality in SpA is not detected at clinical
      examination. US is better than clinical examination in the detection of entheseal
      abnormality of the lower limbs in SpA. A quantitative US score of lower limb
      enthesitis is proposed but further studies are required to validate it in SpA.

PMID- 12228162
TI  - Annual incidence of inflammatory joint diseases in a population based study in
      southern Sweden.
AB  - OBJECTIVE: To estimate the annual incidence of inflammatory joint diseases in a
      population based prospective referral study in an adult population in Kronoberg
      County in southern Sweden. METHODS: The patients were referred from primary
      healthcare centres to the rheumatology department in Vaxjo Central Hospital or to
      the one private rheumatologist in Vaxjo participating in the study. Additionally,
      the hospital records for patients with joint aspirates during the inclusion
      period were checked. The patients were registered as incident cases if the onset
      of the joint inflammation was between 1 May 1999 and 1 May 2000. A systematic
      follow up of incoming referrals was conducted up to 31 January 2001. Children
      under the age of 16 and patients with septic arthritis, crystal arthropathies,
      and osteoarthritis were excluded from the study. RESULTS: A total of 151 new
      cases with inflammatory joint diseases were identified during one year,
      corresponding to a total annual incidence of 115/100 000. Of these, 31 patients
      (21%) had rheumatoid arthritis, the annual incidence being 24/100 000 (for women
      29/100 000, and for men 18/100 000). Reactive arthritis was diagnosed in 37
      patients (24%, annual incidence 28/100 000) and 54 patients had undifferentiated
      arthritis (36%, annual incidence 41/100 000). Eleven patients presented with
      psoriatic arthritis (7%, annual incidence 8/100 000). The incidence of Lyme
      arthritis was small in this non-endemic area, and the incidence of sarcoid
      arthritis corresponded to that in earlier studies. CONCLUSION: This is the first
      prospective population based annual incidence study of early arthritis in Sweden.
      In this population, 36% of the incident cases had undifferentiated arthritis,
      whereas rheumatoid arthritis and reactive arthritis accounted for 45% of the
      cases. The incidence figures compare well with figures reported from other
      countries.

PMID- 12228163
TI  - Synovial macrophage-osteoclast differentiation in inflammatory arthritis.
AB  - BACKGROUND: Pathological bone resorption (marginal erosions and juxta-articular
      osteoporosis) by osteoclasts commonly occurs in rheumatoid arthritis (RA).
      OBJECTIVES: To define the nature of the mononuclear precursor cells from which
      osteoclasts are formed in inflamed synovial tissues and to determine the cellular
      and humoral factors which influence osteoclast differentiation. METHOD:
      Macrophage (CD14+), non-macrophage (CD14-), and unsorted (CD14+/CD14-) synovial
      cell populations from RA and inflammatory/non-inflammatory osteoarthritis (OA)
      synovium were cultured in the presence of receptor activator for nuclear factor
      kappaB ligand (RANKL) and monocyte-colony stimulating factor (M-CSF; in the
      presence/absence of prostaglandin E(2) (PGE(2)), interleukin 1beta (IL1beta),
      tumour necrosis factor alpha (TNFalpha), and IL6). Osteoclast differentiation was
      assessed by expression of tartrate resistant acid phosphatase (TRAP), vitronectin
      receptor (VNR), and lacunar resorption. RESULTS: TRAP+ and VNR+ multinucleated
      cells capable of lacunar resorption were only formed in cultures of CD14+
      containing synovial cell populations (that is, CD14+ and CD14+/CD14- cells). No
      difference in the extent of osteoclast formation was noted in cultures of CD14+
      cells isolated from RA, inflammatory OA, and non-inflammatory OA synovium.
      However, more TRAP+/VNR+ cells and more lacunar resorption was noted in
      CD14+/CD14- cells from RA and inflammatory OA synovial tissues. The addition of
      PGE(2), IL1beta, TNFalpha, and IL6 did not increase RANKL/M-CSF-induced
      osteoclast formation and lacunar resorption of both CD14+/CD14- and CD14+
      synovial cell populations. CONCLUSIONS: Osteoclast precursors in synovial tissues
      are CD14+ monocyte/macrophages. The increase in osteoclast formation in cultures
      of CD14+/CD14- compared with CD14+ synovial cells in RA and inflammatory OA
      points to a role for CD14- cells in promoting osteoclast differentiation and bone
      resorption in inflamed synovial tissues by a mechanism which does not involve a
      direct effect of proinflammatory cytokines/prostaglandins on RANKL-induced
      macrophage-osteoclast differentiation.

PMID- 12228164
TI  - Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20
      monoclonal antibody (rituximab).
AB  - BACKGROUND: Rituximab, a chimeric monoclonal anti-CD20 antibody, has recently
      been used for the treatment of refractory antibody mediated autoimmune diseases
      such as immune mediated thrombocytopenia and haemolytic anaemia. PATIENTS:
      Because of its novel mechanism of action, rituximab was used to treat three
      patients with refractory systemic antibody mediated autoimmune disorders. The
      first patient, a 71 year old woman with idiopathic type II mixed essential
      cryoglobulinaemia, had both dermatological and neurological manifestations with
      marked renal disease attributed to her cryoglobulinaemia. Patient 2, a 73 year
      old woman with Goodpasture's syndrome, was refractory to conventional treatment
      (cyclophosphamide, prednisone, plasmapheresis). She had persistent haemoptysis
      and haematuria and positive antiglomerular basement membrane antibodies. The
      third patient, a 75 year old man with primary biliary cirrhosis, myelodysplasia,
      and systemic immune complex vasculitis, had progressive renal insufficiency, a
      macular erythematous rash, and severe thrombocytopenia. RESULTS: Treatment with
      rituximab resolved all clinical and laboratory manifestations in the three
      patients. CONCLUSIONS: Rituximab may be an important therapeutic agent for the
      treatment of patients refractory or intolerant to corticosteroid or cytotoxic
      treatment, or both.

PMID- 12228165
TI  - Effect of bisphosphonates on viability, proliferation, and dexamethasone-induced
      apoptosis of articular chondrocytes.
AB  - BACKGROUND: Bisphosphonates (BP) increase bone mass in patients with rheumatoid
      arthritis and are effective in the prevention and treatment of steroid-induced
      osteoporosis. However, little is known about their direct effects on
      chondrocytes. OBJECTIVES: To study the influence of BP on articular chondrocytes
      in vitro and to investigate whether BP can prevent steroid-induced apoptosis of
      articular chondrocytes. METHODS: Bovine articular chondrocytes were cultured and
      incubated with different concentrations of clodronate, pamidronate, risedronate,
      or dexamethasone. In the second part of the study, BP were added to the
      chondrocyte cultures one hour before co-incubation with dexamethasone. Viability
      and proliferation were evaluated using propidium iodide staining and tritium
      labelled thymidine incorporation. Apoptosis was measured with annexin V staining
      or the TUNEL method. RESULTS: Only high concentrations (>10(-6) mol/l) of
      clodronate, pamidronate, and risedronate induced a decrease in the viability and
      proliferation of chondrocytes. None of the BP at concentrations ranging from 10(
      12) to 10(-3) mol/l induced apoptosis. Growth retardation and apoptosis induced
      by dexamethasone (10(-7) mol/l) was prevented by addition of pamidronate (10(-6)
      mol/l) or risedronate (10(-8) or 10(-6) mol/l). CONCLUSION: Bisphosphonates in
      therapeutic concentrations are safe for articular chondrocytes in vitro.
      Moreover, pamidronate and risedronate prevent dexamethasone-induced growth
      retardation and apoptosis of chondrocytes. These findings add evidence for a
      chondroprotective effect of nitrogen-containing BP, especially in patients
      treated with corticosteroids.

PMID- 12228166
TI  - Anti-Ro52 reactivity is an independent and additional serum marker in connective
      tissue disease.
AB  - OBJECTIVE: To determine whether anti-Ro52 is an independent serum marker in
      connective tissue disease. METHODS: Over a two year period, 1727 consecutive
      antinuclear antibody (ANA) positive serum samples were analysed in parallel by
      double immunodiffusion with thymus/spleen nuclear extract and by line immunoassay
      with recombinant Ro52, recombinant La/SSB, and natural Ro60. Sera that were only
      reactive towards Ro52 were further analysed by a variety of additional anti
      SSA/Ro detection methods and by specific anti-Ro52 and anti-Ro60 assays. Natural
      purified SSA/Ro was analysed by immunoblot and protein sequencing. RESULTS:
      Analysis of natural purified SSA/Ro (Immunovision, Springdale, AR) showed only
      Ro60 and no immunoreactive Ro52. Consequently, assays based on this substrate
      only identify sera with anti-Ro60 reactivity. Twenty serum samples showed anti
      Ro52 without anti-Ro60 and anti-SSB/La on line immunoassay. By additional
      testing, 2/20 sera were found positive for anti-Ro60 reactivity. The remaining 18
      sera were not identified by any of the classical anti-SSA/Ro assays and were
      considered to be reactive only with Ro52 and not with Ro60. This anti-Ro52
      reactivity was confirmed by natural and recombinant Ro52 in 16/18 cases. 12/18
      sera corresponded to connective tissue diseases. CONCLUSION: Anti-Ro52 positive
      sera without any evidence of anti-Ro60 and anti-La/SSB reactivity can be
      considered as an independent group that is systematically missed by classical
      anti-SSA/Ro detection methods owing to a bias towards anti-Ro60 reactivity. The
      anti-Ro52 sera are precipitin negative, not retrieved by SSA/Ro enzyme linked
      immunosorbent assays (ELISAs) based on natural SSA/Ro, and show no specific ANA
      fluorescence staining pattern. These findings together with the clinical data
      indicate that anti-Ro52 should be considered as an additional and independent
      serum marker.

PMID- 12228167
TI  - Low levels of apoptosis and high FLIP expression in early rheumatoid arthritis
      synovium.
AB  - OBJECTIVES: To define synovial apoptosis with respect to disease duration,
      inflammatory cell type, FLIP (FLICE-like inhibitory protein), and cytokines
      expression in patients with rheumatoid arthritis (RA). METHODS: Synovial biopsy
      specimens from 11 patients with longstanding RA (median disease duration 21
      years) and eight with early RA (median disease duration five months) were
      investigated. Apoptosis (TUNEL method combined with morphological analysis), cell
      surface markers (CD3, CD68), cytokines (interleukin (IL) 1alpha, IL1beta, tumour
      necrosis factor alpha, and IL6), and FLIP expression were evaluated. Computer
      assisted image analysis was used for quantification. RESULTS: The apoptosis level
      in RA synovium was significantly higher in the group of patients with
      longstanding RA than in the patients with early RA (8.8% v 0.6%, p=0.001), while
      the number of macrophages and FLIP expression were higher in the group with early
      disease than in the group with longstanding RA (16.2% v 8.3%, p=0.02 and 31.1% v
      0.2%, p=0.001 respectively). All three markers correlated significantly with
      disease duration (R=-0.7, p<0.001 for FLIP, R=0.6, p=0.001 for apoptosis, and R=
      0.5, p<0.05 for CD68). Cytokine expression and T cell score were not
      significantly different in early RA from longstanding RA. No differences were
      seen between patients treated or not treated with corticosteroids or between
      patients treated or not treated with disease modifying antirheumatic drugs.
      CONCLUSIONS: The findings suggest that RA synovial macrophages are resistant to
      apoptosis in early RA and express high levels of FLIP. During natural or drug
      modified disease progression the apoptotic mechanism may be restored with a
      specific increase of synovial apoptosis in patients with longstanding arthritis.

PMID- 12228168
TI  - Systemic sclerosis following human cytomegalovirus infection.

PMID- 12228169
TI  - A case of orbital myositis associated with rheumatoid arthritis.

PMID- 12228170
TI  - Stiff man syndrome presenting with low back pain.

PMID- 12228171
TI  - A 26 week randomised, double blind, placebo controlled exploratory study of
      sulfasalazine in juvenile onset spondyloarthropathies.

PMID- 12228172
TI  - Leflunomide decreases joint erosions and induces reparative changes in a patient
      with psoriatic arthritis.

PMID- 12228173
TI  - Stress fracture of base of the acromion.

PMID- 12228174
TI  - alpha(1) Antitrypsin deficiency in a patient with systemic vasculitis and primary
      Sjogren's syndrome.

PMID- 12228175
TI  - Steroids cause osteoporosis.

PMID- 12228176
TI  - Sjogren's syndrome criteria.

PMID- 12228177
TI  - A brief history of spa therapy.

PMID- 12228178
TI  - Interindividual differences of human flavin-containing monooxygenase 3: genetic
      polymorphisms and functional variation.
AB  - The human flavin-containing monooxygenase (form 3) (FMO3) participates in the
      oxygenation of nucleophilic heteroatom-containing drugs, xenobiotics, and
      endogenous materials. Currently, six forms of the FMO gene are known, but it is
      FMO3 that is the major form in adult human liver that is likely responsible for
      the majority of FMO-mediated metabolism. The substrate structural feature
      requirements for human FMO3 is beginning to become known to a greater extent and
      a few chemicals extensively metabolized by FMO3 have been reported. Expression of
      FMO3 is species- and tissue-specific, but unlike human cytochrome p450, mammalian
      FMO3 does not appear to be inducible. Interindividual variation in FMO3-dependent
      metabolism of drugs, chemicals, and endogenous material is therefore more likely
      due to genetic effects and not environmental ones. Examples of such
      interindividual variation come from the study of very rare mutations of the human
      FMO3 gene that have been associated with deficient N-oxygenation of dietary
      trimethylamine. Defective trimethylamine N-oxygenation causes trimethylaminuria
      or "fish-like odor syndrome". Information on human FMO3 mutations from
      individuals suffering from the condition of trimethylaminuria has provided
      knowledge about the underlying molecular mechanism(s) for trimethylaminuria. A
      number of common variants of human FMO3 have been reported. Diversification of
      the FMO3 gene may have led to selective advantages and new functions. As more
      examples of human FMO3-mediated metabolism of drugs or new chemical entities are
      discovered in the future, it is possible that FMO3 allelic variation may be shown
      to contribute to interindividual and interethnic variability of FMO-mediated
      metabolism. Human FMO3 may be another example of an environmental gene that
      participates in a protective mechanism to help humans ward off potentially toxic
      exposure of chemicals.

PMID- 12228179
TI  - Reactive intermediates and the dynamics of glutathione transferases.
AB  - Reactive intermediates are a continuous burden in biology and several defense
      mechanisms have evolved. Here we focus on the functions of glutathione
      transferases (GSTs) with the aim to discuss the quantitative aspects of defense
      against reactive intermediates. Humans excrete approximately 0.1 mmol of
      thioether conjugates per day. As the amount of GST active sites in liver is
      approximately 0.5 mmol, it appears that glutathione transferase catalysts are
      present in tremendous excess. In fact, the known catalytic properties of GSTs
      reveal that the enzymes can empty the liver glutathione (GSH) pool in a matter of
      seconds when provided with a suitable substrate. However, based on the urinary
      output of conjugates (or derivatives thereof), individual GSTs turn over (i.e.,
      catalyze a single reaction) only once every few days. Glutathione transferase
      overcapacity reflects the fact that there is a linear relation between GST enzyme
      amount and protection level (provided that GSH is not depleted). Put in a
      different perspective, a few reactive molecules will always escape conjugation
      and reach cellular targets. It is therefore not surprising that signaling systems
      sensing reactive intermediates have evolved resulting in the increase of GSH and
      GST levels. Precisely for this reason, more moderately reactive electrophiles
      (Michael acceptors) are receiving growing interest due to their anticarcinogenic
      properties. Another putative regulatory mechanism involves direct activation of
      microsomal GST1 by thiol-reactive electrophiles through cysteine 49. The
      toxicological significance of low levels of reactive intermediates are of
      interest also in drug development, and here we discuss the use of microsomal GST1
      activation as a surrogate detection marker.

PMID- 12228180
TI  - Effective dosing regimen of 1-aminobenzotriazole for inhibition of antipyrine
      clearance in rats, dogs, and monkeys.
AB  - 1-Aminobenzotriazole (ABT) has been extensively used as a nonspecific inhibitor
      of cytochromes p450 (p450s) in animals for mechanistic studies, and antipyrine
      (AP) has been used as a probe for hepatic oxidative metabolic capacity
      determination in vivo. The method of use of ABT has been variable from lab to lab
      due largely to unknown pharmacokinetics of ABT itself and incomplete information
      on various p450s inhibited. The oral pharmacokinetic profiles of ABT were
      generated in rats, dogs, and monkeys in the dose range of 5 to 200 mg/kg. The
      results showed that after single oral doses of 50 mg/kg in rats, and 20 mg/kg in
      dogs and monkeys, the plasma concentrations were high and were sustained for over
      24 h. In vitro, inhibition of various expressed p450s upon 30-min preincubation
      with ABT (0-500 micro M) showed that CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A4 were
      inhibited in a dose-dependent manner. The intravenous pharmacokinetics of AP also
      was affected in a dose-dependent manner in all species, treated 2 h earlier with
      ABT. Thus, the plasma clearance of AP was inhibited by 88% in rats pretreated
      with 50 mg/kg ABT and 96% in dogs and 83% in monkeys pretreated with 20 mg/kg
      ABT. Based on these data in rats, dogs, and monkeys, and the established safety
      profile of ABT in rats dosed up to 100 mg/kg, a pretreatment at 2 h with a single
      oral dose of ABT at 100 mg/kg in rats (providing 93% inhibition) and 20 mg/kg in
      dogs and monkeys effectively inhibited the clearance of the probe compound.

PMID- 12228181
TI  - Metabolic activation of 4-hydroxyanisole by isolated rat hepatocytes.
AB  - A tyrosinase-directed therapeutic approach for treating malignant melanoma uses
      depigmenting phenolic prodrugs such as 4-hydroxyanisole (4-HA) for oxidation by
      melanoma tyrosinase to form cytotoxic o-quinones. However, in a recent clinical
      trial, both renal and hepatic toxicity were reported as side effects of 4-HA
      therapy. In the following, 4-HA (200 mg/kg i.p.) administered to mice caused a 7
      fold increase in plasma transaminase toxicity, an indication of liver toxicity.
      Furthermore, 4-HA induced-cytotoxicity toward isolated hepatocytes was preceded
      by glutathione (GSH) depletion, which was prevented by cytochrome p450 inhibitors
      that also partly prevented cytotoxicity. The 4-HA metabolite formed by
      NADPH/microsomes and GSH was identified as a hydroquinone mono-glutathione
      conjugate. GSH-depleted hepatocytes were much more prone to cytotoxicity induced
      by 4-HA or its reactive metabolite hydroquinone (HQ). Dicumarol (an
      NAD(P)H/quinone oxidoreductase inhibitor) also potentiated 4-HA- or HQ-induced
      toxicity whereas sorbitol, an NADH-generating nutrient, prevented the
      cytotoxicity. Ethylenediamine (an o-quinone trap) did not prevent 4-HA-induced
      cytotoxicity, which suggests that the cytotoxicity was not caused by o-quinone as
      a result of 4-HA ring hydroxylation. Deferoxamine and the antioxidant
      pyrogallol/4-hydroxy-2,2,6,6-tetramethylpiperidene-1-oxyl (TEMPOL) did not
      prevent 4-HA-induced cytotoxicity, therefore excluding oxidative stress as a
      cytotoxic mechanism for 4-HA. A negligible amount of formaldehyde was formed when
      4-HA was incubated with rat microsomal/NADPH. These results suggest that the 4-HA
      cytotoxic mechanism involves alkylation of cellular proteins by 4-HA epoxide or p
      quinone rather than involving oxidative stress.

PMID- 12228182
TI  - Quaternary ammonium-linked glucuronidation of 1-substituted imidazoles by liver
      microsomes: interspecies differences and structure-metabolism relationships.
AB  - N-Glucuronidation at an aromatic tertiary amine of 5-membered polyaza ring
      systems was investigated for a model series of eight 1-substituted imidazoles in
      liver microsomes from five species. The major objectives were to investigate
      substrate specificities of the series in human microsomes and interspecies
      variation for the prototype molecule, 1-phenylimidazole. The formed quaternary
      ammonium-linked metabolites were characterized by positive ion electrospray mass
      spectrometry. The incubation conditions for the N-glucuronidation of 1
      substituted imidazoles were optimized; where for membrane disrupting agents,
      alamethicin was more effective than the detergents examined. The need to optimize
      alamethicin concentration was indicated by 4-fold interspecies variation in
      optimal concentration and by a change in effect from removal of glucuronidation
      latency to inhibition on increasing concentration. For the four species with
      quantifiable N-glucuronidation of 1-phenylimidazole, there were 8- and 18-fold
      variations in the determined apparent K(m) (range, 0.63 to 4.8 mM) and V(max)
      (range, 0.08 to 1.4 nmol/min/mg of protein) values, respectively. The apparent
      clearance values (V(max)/K(m)) were in the following order: human congruent with
      guinea pig congruent with rabbit > rat congruent with dog (no metabolite
      detected). Monophasic kinetics were observed for the N-glucuronidation of seven
      substrates by human liver microsomes, which suggests that one enzyme is involved
      in each metabolic catalysis. No N-glucuronidation was observed for the substrate
      containing the para-phenyl substituent with the largest electron withdrawing
      effect, 1-(4-nitrophenyl)imidazole. Linear correlation analyses between apparent
      microsomal kinetics and substrate physicochemical parameters revealed significant
      correlations between K(m) and lipophilicity (pi(para) or log P values) and
      between V(max)/K(m) and both electronic properties (sigma(para) value) and pKa.

PMID- 12228183
TI  - In vitro metabolism of R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo
      [1,2,3-de]1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate, a cannabinoid
      receptor agonist.
AB  - R(+)-[2,3-Dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2, 3-de]1,4-benzoxa
      zinyl]-(1-naphthalenyl methanone mesylate (WIN55212-2) is a potent cannabinoid
      receptor agonist that has been found to exhibit antinociceptive activity and to
      inhibit brain cyclooxygenase. The metabolism of WIN55212-2 has not been reported,
      and it is unknown whether its metabolites retain any agonist properties. In this
      study, in vitro metabolism of WIN55212-2 in rat liver microsome was investigated.
      The metabolic profile was obtained using high-performance liquid chromatography
      (HPLC) with UV and mass spectrometry detectors. The HPLC chromatogram revealed
      two major and at least six minor metabolites derived from the parent compound ([M
      + H](+) = m/z 427). The two major metabolites (structural isomers at m/z 461),
      constituting 60 to 75% of the total metabolites, were each identified as
      dihydrodiol metabolites resulting from the arene oxide pathway. The minor
      metabolites were all detected as protonated molecules, three of which appeared at
      m/z 477, corresponding to structural isomers of trihydroxylated parent compound;
      another two appeared at m/z 443, representing monohydroxylated isomers; and
      another was observed at m/z 425, and was assigned as a dehydrogenation product.
      These structural assignments are based on HPLC/tandem mass spectrometry and NMR
      analysis. Metabolic pathways have been proposed to account for the various
      metabolites observed. Two major metabolites have been isolated in pure form,
      allowing future receptor binding studies to be conducted.

PMID- 12228184
TI  - Flavin-containing monooxygenase activity in hepatocytes and microsomes: in vitro
      characterization and in vivo scaling of benzydamine clearance.
AB  - Liver microsomes, and more recently cryopreserved hepatocytes, are commonly used
      in the in vitro characterization of the metabolism of new xenobiotics. The flavin
      containing monooxygenases (FMO) are a major non p450 oxidase present in liver
      microsomes and hepatocytes. Since FMO is known to be thermally labile, and this
      enzyme may be involved in the metabolic clearance of some drugs, we sought to
      more completely characterize the metabolic competency of this enzyme in
      cryopreserved hepatocytes and in liver microsomes preincubated under various
      conditions using benzydamine as an in vitro and in vivo probe. The metabolism of
      benzydamine to its major metabolite, the N-oxide, is mediated by FMO3 in humans.
      We found that the in vitro microsomal t(1/2) was 70% longer when incubations were
      prewarmed at 37 degrees C in the absence of NADPH compared with prewarming in the
      presence of an NADPH-regenerating system, and N-oxide formation was inhibited
      >99%. Interestingly, the in vivo clearance predicted from these incubations and
      from human hepatocytes overpredicted the observed clearance of benzydamine in
      humans (>10.5 versus 2.4 ml/min/kg). In contrast, rat hepatocytes successfully
      predicted rat in vivo benzydamine clearance to within approximately 30% (>68
      versus 48 ml/min/kg). Benzydamine N-oxidation in liver microsomes from all common
      preclinical species demonstrated heat sensitivity. This information should be
      considered when extrapolating metabolism data of xenobiotics from these in vitro
      systems.

PMID- 12228185
TI  - Implication of P450-metabolite complex formation in the nonlinear
      pharmacokinetics and metabolic fate of (+/-)-(1'R*,3R*)-3-phenyl-1-[(1',2',3',4'
      tetrahydro-5',6'-methylene-dioxy-1'-naphthalenyl) methyl] pyrrolidine
      methanesulfonate (ABT-200) in dogs.
AB  - Following a single oral or intravenous administration of the R,R(+) and S,S(-)
      (14)C-pseudoracemate of (+/-)-(1'R*,3R*)-3-phenyl-1-[(1',2',3',4'-tetrahydro
      5',6'-methylene-dioxy-1'-naphthalenyl) methyl] pyrrolidine methanesulfonate (ABT
      200/I) to dogs, a total of six (R,R[+]) and eight (S,S[-]) metabolites were
      identified by high-pressure liquid chromatography/mass spectral techniques.
      Greater than 99% of the dose was eliminated as metabolites indicating that the
      clearance of I was predominantly metabolic. The catechol was the major excreted
      metabolite (fecal), whereas the urine and bile predominantly contained
      metabolites resulting from secondary biotransformation of the catechol via O
      methylation, glucuronidation, and sulfation. After a single 12 mg/kg oral dose of
      racemic I to dogs, the mean area under the plasma curve (AUC(0-24h)) averaged
      4.55 micro g. h/ml, with an apparent plasma clearance value of 2.70 l/h. kg.
      After 14 daily doses, the apparent plasma clearance was 3.5-fold lower (0.78 l/h.
      kg) and the AUC(0-24h) about 4-fold higher (18.58 micro g. h/ml). Isolation of
      liver microsomes from these animals indicated that a cytochrome p450 (p450)
      metabolite complex (MI complex) was formed in the liver after both single and
      multiple dosing. The mean concentration of the MI complex 24 h after a single
      dose averaged 31 pmol/mg of microsomal protein, whereas the amount in the animals
      given multiple doses of I averaged 163 pmol/mg. There was a positive correlation
      (R(2) = 0.993) between the plasma AUC for I and the amount of the MI complex
      found in the liver of each animal. Formation of the MI complex was demonstrated
      in vitro in control dog liver microsomes, was NADPH-dependent, and was
      dissociated from p450 with 2-methylbenzimidazole. In vitro preincubation studies
      indicated that I was a mechanism-based inhibitor and that formation of the
      complex inhibited catechol formation. These results demonstrate that the liver
      p450s that metabolize I form an inhibitory MI complex after in vivo
      administration in dogs. Formation of the complex increases during multiple dosing
      and inhibits the enzymes from further metabolism of I resulting in nonlinear
      pharmacokinetics.

PMID- 12228186
TI  - Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450
      enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin.
AB  - The ability of tricyclic antidepressants (TCAs) to inhibit phenytoin p
      hydroxylation was evaluated in vitro by incubation studies of human liver
      microsomes and cDNA-expressed cytochrome p450s (p450s). The TCAs tested were
      amitriptyline, imipramine, nortriptyline, and desipramine. Amitriptyline and
      imipramine strongly and competitively inhibited phenytoin p-hydroxylation in
      microsomal incubations (estimated K(i) values of 5.2 and 15.5 micro M,
      respectively). In contrast, nortriptyline and desipramine produced only weak
      inhibition. In the incubation study using cDNA-expressed P450s, both CYP2C9 and
      CYP2C19 catalyzed phenytoin p-hydroxylation, whereas TCAs inhibited only the
      CYP2C19 pathway. All of the TCAs tested inhibited CYP2D6-catalyzed
      dextromethorphan-O-demethylation competitively, with estimated K(i) values of
      31.0, 28.6, 7.9, and 12.5 micro M, respectively. The tertiary amine TCAs,
      amitriptyline and imipramine, also inhibited CYP2C19-catalyzed S-mephenytoin 4'
      hydroxylation (estimated K(i) of 37.7 and 56.8 micro M, respectively). The
      secondary amine TCAs, nortriptyline and desipramine, however, showed minimal
      inhibition of CYP2C19 (estimated IC(50) of 600 and 685 micro M, respectively).
      None of the TCAs tested produced remarkable inhibition of any other p450
      isoforms. These results suggest that TCAs inhibit both CYP2D6 and CYP2C19 and
      that the interaction between TCAs and phenytoin involves inhibition of CYP2C19
      catalyzed phenytoin p-hydroxylation.

PMID- 12228187
TI  - Interindividual variability and tissue-specificity in the expression of
      cytochrome P450 3A mRNA.
AB  - The elucidation of the individual contributions of the four CYP3A genes to the
      overall CYP3A activity has been hampered by similarities in their sequence and
      function. We investigated the expression of CYP3A mRNA species in the liver and
      in various other tissues using gene-specific TaqMan probes. CYP3A4 transcripts
      were the most abundant CYP3A mRNA in each of the 63 white European livers tested
      and accounted on average for 95% of the combined CYP3A mRNA pool. CYP3A5 and
      CYP3A7 each contributed on average 2%, whereas CYP3A43 contributed 0.3%
      transcripts to this pool. Fourteen percent of livers exhibited an increased share
      of CYP3A5 transcripts (range 4-20%). These livers were either heterozygous for
      the marker of the CYP3A5 polymorphism, the CYP3A5*1A allele, or expressed very
      low levels of CYP3A4 mRNA. The CYP3A7 expression was bimodal, and it was
      increased in 15% livers. CYP3A4 was the dominant CYP3A in the intestine, followed
      by CYP3A5. CYP3A5 and CYP3A7, but not CYP3A4, were also expressed in the adrenal
      gland and in the prostate, whereas only CYP3A5 was detected in the kidney. These
      three tissues were shown to express much lower levels of pregnane X receptor mRNA
      than the intestine, indicating possibly a different mode of regulation of CYP3A
      expression. Expression of CYP3A genes was undetectable in peripheral blood
      lymphocytes. In summary, these assays and results should aid in our efforts to
      further dissect the regulation and the physiological and pharmacological
      significance of CYP3A isozymes.

PMID- 12228188
TI  - Metabolism and pharmacokinetics of N'-nitrosonornicotine in the patas monkey.
AB  - N'-Nitrosonornicotine (NNN) is present in significant quantities in tobacco and
      tobacco smoke and is believed to play an important role as a cause of cancer in
      people who use tobacco products. Biomarkers of NNN uptake in humans such as
      urinary metabolites would be useful for assessing cancer risk. Previous studies,
      carried out almost exclusively in rodents, have characterized urinary metabolites
      of NNN, but none of these would be suitable as a biomarkers of NNN uptake in
      humans. Therefore, we studied NNN metabolism in the patas monkey. Monkeys were
      treated intravenously with [5-(3)H]NNN, which has tritium in the pyridine ring.
      Blood and urine samples were collected at timed intervals. Six urinary
      metabolites were observed by high-performance liquid chromatography (HPLC) and
      were identified by their spectral properties and/or comparison to appropriate
      standards as follows: metabolite (% of radioactivity eluting from HPLC +/- S.D.,
      n = 3 monkeys); 4-hydroxy-4-(3-pyridyl)butyric acid (43.8 +/- 4.0); 4-oxo-4-(3
      pyridyl) butyric acid (2.7 +/- 0.66); norcotinine (13.1 +/- 2.7); norcotinine-1N
      oxide (16.5 +/- 1.3); 3'-hydroxynorcotinine (16.9 +/- 2.0); 3'-(O-beta-D
      glucopyranuronosyl)hydroxynorcotinine (5.4 +/- 1.0); and unchanged NNN (0.63 +/-
      0.15). The two major metabolites in serum were 4-hydroxy-4-(3-pyridyl)butyric
      acid and norcotinine. NNN was rapidly metabolized to 4-hydroxy-4-(3
      pyridyl)butyric acid, whereas the formation of norcotinine and 3'
      hydroxynorcotinine were somewhat delayed. The results of this study demonstrate
      substantial differences between NNN metabolism in the rodent and patas monkey.
      Metabolism of NNN to norcotinine and its derivatives was far more prevalent in
      the patas monkey than in the rat. 3'-Hydroxynorcotinine and its O-glucuronide may
      be formed from NNN via alpha-oximinonornicotine or isomyosmine. There was no
      evidence that it was formed via norcotinine, although this pathway could not be
      excluded. 3'-Hydroxynorcotinine could potentially be a biomarker of NNN uptake in
      humans.

PMID- 12228189
TI  - Cefazolin administration and 2-methyl-1,3,4-thiadiazole-5-thiol in human tissue:
      possible relationship to hypoprothrombinemia.
AB  - Cephalosporin antibiotics with structures that include the heterocyclic leaving
      group 1-methyltetrazole-5-thiol (MTT) can cause hypoprothrombinemia and
      hemorrhage as a result of MTT-dependent inhibition of the gamma-carboxylation of
      glutamate. The structure of cefazolin also includes a heterocyclic thiol, 2
      methyl-1,3,4-thiadiazole-5-thiol (MTD), and this compound can also inhibit the
      gamma-carboxylation of glutamate. However, unlike MTT, which is known to be
      present in vivo after the administration of drugs that include this structure,
      there have been no reports that MTD is present in vivo after cefazolin
      administration. We set out to determine whether MTD might be present in the
      tissues of patients treated with cefazolin prior to surgery. To do that, we took
      advantage of the fact that heterocyclic thiols can undergo S-methylation
      catalyzed by the genetically polymorphic drug-metabolizing enzyme thiopurine S
      methyltransferase (TPMT). Initially, we tested recombinant human TPMT as a
      "reagent" to S-methylate MTD. MTD was a substrate for TPMT-catalyzed S
      methylation, with an apparent K(m) value of 63 micro M. Recombinant TPMT, with
      [(14)C-methyl]S-adenosyl-L-methionine as a cosubstrate, was then used to
      radioactively label a methyl acceptor substrate present in liver and kidney
      cytosol preparations from patients who had been treated preoperatively with
      cefazolin. Pooled renal cytosol from 10 of those patients was used to purify and
      isolate the methylated product by reverse-phase high-performance liquid
      chromatography. That methylated compound coeluted with S-methyl MTD. When the
      methylated product was subjected to tandem mass spectrometry, it was identified
      as S-methyl MTD. Therefore, MTD is present in the tissues of patients treated
      with cefazolin. These observations also raise the possibility that the TPMT
      genetic polymorphism may represent a risk factor for cefazolin-induced
      hypoprothrombinemia since subjects who genetically lack TPMT would be unable to
      catalyze this MTD biotransformation pathway.

PMID- 12228190
TI  - Comparison of in vitro preparations for semi-quantitative prediction of in vivo
      drug metabolism.
AB  - Various in vitro preparations were compared with respect to their ability to
      mimic in vivo metabolism. For this purpose, S9-liver homogenate, microsomes,
      cryopreserved hepatocytes, cryopreserved liver slices and fresh liver, lung,
      kidney, and intestinal slices were incubated with three drugs in development,
      which are metabolized in vivo by a wide range of biotransformation pathways.
      Metabolites were identified and quantified with liquid chromatography-mass
      spectometry/UV from the in vitro incubations and compared with metabolite
      patterns in feces, urine, and bile of dosed rats. In vitro systems with intact
      liver cells produced the same metabolites as the rat in vivo and are a valuable
      tool to study drug metabolism. Phase I metabolites were almost all conjugated in
      intact cells, whereas S9-homogenate only conjugated by sulfation and N
      acetylation. Microsomes and S9-homogenate are useful to study phase I metabolism
      but not for the prediction of in vivo metabolism. Extra-hepatic organ slices did
      not form any metabolites that were not produced by liver cells, but the relative
      amounts of the various metabolites differed considerably. Small intestinal slices
      were more active than liver slices in the formation of the N-glucuronide of
      compound C, which is the major metabolite in vivo. When the relative contribution
      of liver and small intestinal slices to the metabolism of this compound was taken
      into account, it appeared that the in vivo metabolite pattern could be well
      predicted. Results indicate that for adequate prediction of in vivo metabolism,
      fresh or cryopreserved liver slices or hepatocytes in combination with slices of
      the small intestines should be used.

PMID- 12228191
TI  - Sulfoxides as urinary metabolites of S-allyl-L-cysteine in rats: evidence for the
      involvement of flavin-containing monooxygenases.
AB  - S-Allyl-L-cysteine (SAC), a component of garlic and a metabolite of allyl
      halides, is a known substrate for multiple flavin-containing monooxygenases
      (FMOs). In the current study, we characterize the in vivo SAC metabolism by
      investigating the presence of SAC, N-acetyl-S-allyl-L-cysteine (NASAC), and their
      corresponding sulfoxides in the urine of rats given SAC (200 or 400 mg/kg i.p.).
      In some experiments, rats were given aminooxyacetic acid (AOAA), an inhibitor of
      cysteine conjugate beta-lyase, or methimazole, an alternative FMO substrate, 30
      min prior to treatment with 200 mg/kg SAC. Nearly 40 to 50% of the dose was
      recovered in the 24-h collection period. In all treatment groups, the majority of
      the metabolites were excreted within 8 h. The major metabolites detected were
      NASAC and NASAC sulfoxide (NASACS; nearly 30-40% and 5-10% of the dose,
      respectively). Only small amounts of the dose (approximately 1.5%) were recovered
      as SAC and SAC sulfoxide (SACS). Methimazole pretreatment significantly reduced
      amounts of both SACS and NASACS detected in the urine when compared with rats
      given SAC only, whereas AOAA pretreatment had no effect. In vitro assays using
      rat liver microsomes were also carried out to compare the sulfoxidation rates of
      SAC and NASAC. The results showed that SAC was much more readily oxidized than
      NASAC. Collectively, the results provide evidence for the involvement of FMOs in
      the in vivo metabolism of SAC and that SAC is a much better substrate for FMOs
      than its corresponding mercapturic acid.

PMID- 12228192
TI  - Diclofenac-induced inactivation of CYP3A4 and its stimulation by quinidine.
AB  - Incubation of human liver microsomes with diclofenac in the presence of NADPH
      resulted in a decrease in testosterone 6 beta-hydroxylation activity. The
      decrease in the activity followed time- and concentration-dependent kinetics,
      required oxidative metabolism, and was resistant to reduced glutathione,
      suggesting that diclofenac causes a mechanism-based inactivation of cytochrome
      p450 (p450) 3A4 (CYP3A4). The inactivation was reproduced by using microsomes
      from B-lymphoblastoid cell lines expressing CYP3A4 instead of human liver
      microsomes. No other monooxygenase activities measured as indexes of p450
      enzymes; CYP2C8, CYP2C9, or CYP2C19 was inactivated by the same incubation
      procedure. Quinidine, a stimulant of CYP3A4-mediated diclofenac 5-hydroxylation,
      did not affect the inactivation of CYP3A4 assessed by testosterone 6 beta
      hydroxylation activity but accelerated the inactivation assessed by diazepam 3
      hydroxylation activity. These results supported the idea that diclofenac 5
      hydroxylation is involved in the inactivation of CYP3A4 and described for the
      first time a stimulation of mechanism-based inactivation attributable to CYP3A4
      heterotropic cooperativity. Preincubation of human liver microsomes with 5
      hydroxydiclofenac instead of diclofenac did not cause the inactivation of CYP3A4,
      suggesting that 5-hydroxydiclofenac is not a precursor of a postulated reactive
      metabolite that inactivates CYP3A4, and thus 5-hydroxylation step is critical to
      inactivation of CYP3A4.

PMID- 12228193
TI  - Pediatric Hodgkin's therapy: time for a paradigm shift.

PMID- 12228194
TI  - Endostatin: are the 2 years up yet?

PMID- 12228195
TI  - The "cure" for cancer: can the media report the hope without the hype?

PMID- 12228196
TI  - Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy
      for children with Hodgkin's disease who achieve a complete response to
      chemotherapy.
AB  - PURPOSE: Current standard therapy for children and adolescents with Hodgkin's
      disease includes combination chemotherapy and low-dose involved-field radiation
      (LD-IFRT). Because radiation may be associated with adverse late effects, the
      Children's Cancer Group (CCG) investigated whether radiation could be omitted in
      patients achieving a complete response to initial chemotherapy without
      jeopardizing the excellent outcome obtained with combined-modality therapy.
      PATIENTS AND METHODS: Between January 1995 and December 1998, 829 eligible
      patients were enrolled onto CCG 5942. A total of 501 patients who achieved an
      initial complete response after risk-adapted combination chemotherapy were
      randomized to receive LD-IFRT or no further treatment. Event-free survival (EFS)
      and overall survival were assessed from the date of study entry or the date of
      randomization, as appropriate. RESULTS: The projected 3-year EFS from study entry
      for the entire cohort was 87% +/- 1.2%. Among patients who achieved a complete
      response to initial chemotherapy, 92% +/- 1.9% of those randomized to receive LD
      IFRT were alive and disease free 3 years after randomization, versus 87% +/- 2.2%
      for patients randomized to receive no further therapy (stratified log-rank test;
      P =.057). With an "as-treated" analysis, 3-year EFS after randomization for the
      radiation cohort was 93% +/- 1.7% versus 85% +/- 2.3% for patients receiving no
      further therapy (stratified log-rank test; P =.0024). Three-year survival
      estimates for patients treated with and without LD-IFRT were 98% +/- 1.1% for
      patients who received radiation and 99% +/- 0.5% for patients who did not receive
      radiation. CONCLUSION: LD-IFRT after an initial complete response to risk-adapted
      chemotherapy improved EFS. At this time, there is no survival advantage for LD
      IFRT, but follow-up remains short.

PMID- 12228197
TI  - Phase I clinical trial of recombinant human endostatin administered as a short
      intravenous infusion repeated daily.
AB  - PURPOSE: To perform a phase I trial of recombinant human endostatin
      (rhEndostatin; EntreMed, Rockville, MD) given as a daily 20-minute intravenous
      (IV) injection in adult patients with refractory solid tumors. PATIENTS AND
      METHODS: The daily dose was increased from 15 to 240 mg/m(2) by a factor of 100%
      in cohorts of three patients. In the absence of dose-limiting toxicity,
      uninterrupted treatment was continued until the tumor burden increased by more
      than 50% from baseline. Correlative studies included dynamic contrast-enhanced
      magnetic resonance imaging of tumor blood flow, urinary vascular endothelial
      growth factor and basic fibroblast growth factor levels, rhEndostatin serum
      pharmacokinetics, and monitoring of circulating antibodies to rhEndostatin.
      RESULTS: There were no notable treatment related toxicities among 15 patients
      receiving a total of 50 monthly cycles of rhEndostatin. One patient with a
      pancreatic neuroendocrine tumor had a minor response and two patients showed
      disease stabilization. Linearity in the pharmacokinetics of rhEndostatin was
      indicated by dose-proportionate increases in the area under the curve for the
      first dose and the peak serum concentration at steady state. Daily systemic
      exposure to rhEndostatin in patients receiving 240 mg/m(2)/d was approximately
      50% lower than that provided by the therapeutically optimal dose in preclinical
      studies. CONCLUSION: rhEndostatin administered as a 20-minute daily IV injection
      at doses up to 240 mg/m(2) showed no significant toxicities. Evidence of clinical
      benefit was observed in three patients. Due to high variability between the peak
      and trough serum concentrations associated with the repeated short IV infusion
      schedule, daily serum drug levels only briefly exceeded concentrations necessary
      for in vitro antiangiogenic effects.

PMID- 12228198
TI  - Study of the media's potential influence on prospective research participants'
      understanding of and motivations for participation in a high-profile phase I
      trial.
AB  - PURPOSE: To describe prospective participants' initial source of information
      about, understanding of, and motivation to participate in a phase I clinical
      trial of the antiangiogenesis agent human recombinant endostatin. PATIENTS AND
      METHODS: We surveyed 100 of 130 persons referred to the endostatin trial between
      October 1999 and November 2000 and analyzed media coverage of the agent from 1997
      to 2000. RESULTS: Forty-seven percent of survey respondents first heard about the
      trial from media reports. Fifty-one percent of these subsequently contacted their
      physicians. Thirty-three percent of respondents correctly understood the purpose
      of the trial. Seventy-nine respondents were interviewed before they met trial
      investigators to discuss the trial. Of these, those who first heard about
      endostatin from the media were five times more likely to understand correctly the
      trial's purpose than those who first heard from other sources. Seventy-four
      percent (70 of 95) of respondents cited hope for personal benefit as the main
      reason for their willingness to enroll. Those who first heard about endostatin
      from the media were no more motivated by hope of personal benefit (77%) than
      those who first heard from other sources (71%) (P =.46). Ninety-nine percent of
      all respondents cited "joining the study gives me hope" as a contributing factor
      in their decision making about the trial. CONCLUSION: Media coverage prompted
      prospective participants to contact their physicians but did not seem to hinder
      understanding nor could it be shown to heighten their hope for personal benefit.

PMID- 12228199
TI  - Phase I study of recombinant human endostatin in patients with advanced solid
      tumors.
AB  - PURPOSE: Endostatin, a 20-kd fragment of collagen XVIII, is a potent inhibitor of
      angiogenesis. We evaluated recombinant human endostatin (rh-Endo) in a phase I
      trial designed to assess safety, pharmacokinetics, and serum markers of
      angiogenesis in patients with solid tumors. PATIENTS AND METHODS: Twenty-six
      patients were enrolled onto a dose-finding trial of rh-Endo administered as an
      intravenous bolus over a 20-minute period once daily. Three patients each were
      treated at dose levels of 15, 30, 60, 120, 180, and 600 mg/m(2)/d, and seven
      patients were treated at 300 mg/m(2)/d. Treatment consisted of a minimum of two
      28-day cycles. Evaluations included noninvasive imaging, pharmacokinetics, and
      serum biomarkers. RESULTS: Twenty-five patients were treated with rh-Endo.
      Treatment was well tolerated; there were no dose-limiting toxic effects.
      Bacteremia from frequent central line access was the most common problem. The
      pharmacokinetic disposition of rh-Endo was linear and best described using a two
      compartmental open model. The overall mean half-life was 10.7 +/- 4.1 hours. A
      dose of 300 mg/m(2) achieved an area under the concentration-time curve
      associated with activity in preclinical models. In two patients, there was
      evidence of antitumor activity, but no responses were seen. Serum markers of
      angiogenic activity did not provide insight into rh-Endo's activity. Serum
      antibodies were observed against both rh-Endo and the Pichia pastoris vector, but
      no allergic reactions were observed. CONCLUSION: rh-Endo was safe and well
      tolerated. rh-Endo pharmacokinetic profiles achieved area under the concentration
      time curves associated with activity in preclinical models. Evidence of minor
      antitumor activity was observed and further studies are indicated.

PMID- 12228200
TI  - Development of biologic markers of response and assessment of antiangiogenic
      activity in a clinical trial of human recombinant endostatin.
AB  - PURPOSE: Angiogenesis is a target for the treatment of cancer and other diseases,
      and its complex biology suggests that establishing the appropriate dose and
      schedule for antiangiogenic treatment will require extensive study. We present
      the initial results of a dose-finding clinical trial of recombinant human
      endostatin (rh-Endo) that examined potential surrogates for response to
      antiangiogenic therapy. PATIENTS AND METHODS: Twenty-five patients were treated
      with escalating doses of rh-Endo. Positron emission tomography (PET) was used to
      assess tumor blood flow (with [15O]H2O) and metabolism (with
      [18F]fluorodeoxyglucose) before the start of therapy and then every 4 weeks. To
      directly assess the effects of rh-Endo on endothelial cells within the tumors,
      biopsy specimens of tumor tissue were obtained before therapy and again at 8
      weeks and evaluated for endothelial cell and tumor cell apoptosis. RESULTS: Tumor
      blood flow and metabolism as measured by PET scans generally decreased with
      increasing doses of rh-Endo; however, the effects were complex and in some
      analyses nonlinear. Tumor biopsy analysis revealed a significant increase in
      tumor cell apoptosis (P =.027) and endothelial cell apoptosis (P =.027) after 8
      weeks of therapy. However, there was no statistically significant relationship
      between rh-Endo dose and induction of tumor cell or endothelial cell apoptosis.
      CONCLUSION: These initial data suggest that rh-Endo has measurable effects on
      tumor blood flow and metabolism and induces endothelial and tumor cell apoptosis
      even in the absence of demonstrable anticancer effects. Further study and
      validation of these biomarkers in the context of antiangiogenic therapy will be
      required.

PMID- 12228201
TI  - Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839
      is generally well-tolerated and has activity in non-small-cell lung cancer and
      other solid tumors: results of a phase I trial.
AB  - PURPOSE: To investigate safety, tolerability, dose-related pharmacologic
      properties, and pharmacodynamics of ZD1839 (gefinitib, Iressa; AstraZeneca
      Pharmacueticals, Wilmington, DE), an epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitor, in patients with solid tumor types known to express or
      highly express EGFR. METHODS: This was an open-label, phase I, dose escalation
      safety/tolerability trial of oral ZD1839 (150 to 1,000 mg/d), administered once
      daily for 28-continuous-day cycles until disease progression or undue toxicity.
      RESULTS: Of 71 (69 assessable for safety; 58 for efficacy) patients at seven dose
      levels, most had non-small-cell lung (n = 39) or head and neck (n = 18) cancer,
      and 68 of 71 patients received prior cancer therapy (two or more regimens in 54
      patients [78%]). Diarrhea and rash, the primary dose-limiting toxicities (DLTs),
      occurred at 800 mg. Frequent treatment-related grade 1/2 adverse events were
      diarrhea (55%), asthenia (44%), and acne-like follicular rash (46%). At doses
      >or= 800 mg, 45% of patients required dose reductions. No increased or cumulative
      toxicity was observed over 250 patient-months of exposure. Pharmacokinetic
      analysis showed that steady-state occurred by day 7, interpatient exposure was
      more variable than intrapatient exposure, and variability of exposure did not
      change with dose. One patient experienced a partial response, but antitumor
      activity manifested mainly as prolonged stable disease (45% of patients >or= 3
      months, 22% >or= 6 months, and 7.2% >or= 1 year). No relationship between dose,
      response, or duration on study was observed. CONCLUSION: Rash and diarrhea,
      generally mild and tolerable at doses <or= 600 mg/d, were DLTs at 800 mg/d
      (maximum-tolerated dose). Antitumor activity was observed at all doses.
      Pharmacokinetic analyses confirmed suitability of once-daily oral dosing.

PMID- 12228202
TI  - Effects of 5,6-dimethylxanthenone-4-acetic acid on human tumor microcirculation
      assessed by dynamic contrast-enhanced magnetic resonance imaging.
AB  - PURPOSE: 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) causes vascular shutdown in
      preclinical models. Dynamic contrast-enhanced (DCE) magnetic resonance imaging
      (MRI) studies were performed in the phase I trials to examine changes related to
      blood flow and permeability in tumor and muscle. PATIENTS AND METHODS: Sixteen
      patients treated with DMXAA from 500 to 4,900 mg/m(2) had DCE-MRI examinations
      before and after treatment. The maximum gradient, the maximum enhancement, and
      the area under the signal-intensity-time curve (AUC) over the first 90 seconds
      were calculated for each pixel in regions of interest (ROIs) in muscle and tumor,
      and the median value for each ROI was obtained. Changes after treatment were
      compared with 95% limits of agreement for an individual and for groups using data
      from our reproducibility study. RESULTS: Nine of 16 patients had significant
      reductions in AUC 24 hours after the first dose of DMXAA, and eight of 11
      patients had reductions of up to 66% in AUC 24 hours after the last dose. Mean
      reductions in gradient, enhancement, and AUC were 25%, 18%, and 31%,
      respectively, 24 hours after the last dose, significantly greater than the 95%
      limits of change for a group of 11 patients. Enhancement and AUC in muscle 24
      hours after the first dose were significantly reduced, but no significant changes
      were seen 24 hours after the last dose. CONCLUSION: DMXAA significantly reduces
      DCE-MRI parameters related to tumor blood flow, over a wide dose range,
      consistent with the reported tumor vascular targeting activity. Further clinical
      evaluation of DMXAA is warranted.

PMID- 12228203
TI  - Pegylated interferon alfa-2b treatment for patients with solid tumors: a phase
      I/II study.
AB  - PURPOSE: The efficacy of interferon alfa has been established in treating
      advanced melanoma and renal cell carcinoma (RCC) patients. We conducted a phase
      I/II study to determine the maximum-tolerated dose (MTD), the safety and
      tolerability, and the preliminary efficacy of once-weekly pegylated interferon
      alfa-2b (IFNalpha-2b) in patients with advanced solid tumors (primarily RCC).
      PATIENTS AND METHODS: To determine the MTD, 35 patients with a variety of
      advanced solid tumors received 0.75 to 7.5 micro g/kg/wk of pegylated IFNalpha-2b
      by subcutaneous injection for 12 weeks. An additional 35 previously untreated RCC
      patients received 6.0 and 7.5 micro g/kg/wk for up to 12 weeks. Patients with a
      response or stable disease after 12 weeks were eligible for the extension
      protocol and were treated for up to 1 year or until disease progression. RESULTS:
      The MTD for pegylated IFNalpha-2b at 12 weeks was 6.0 micro g/kg/wk. One year of
      6.0 micro g/kg/wk was well tolerated with appropriate dose modification; no grade
      3 or 4 fatigue occurred, and safety was comparable with that with nonpegylated
      IFNalpha-2b. The most common nonhematologic adverse events included mild to
      moderate nausea, anorexia, and fatigue. Six patients had grade 3 or 4 hematologic
      toxicity. Twenty-nine patients continued on the extension protocol. Four patients
      had a complete response, and five patients had a partial response. Among 44
      previously untreated RCC patients, the objective response rate was 14%. Median
      survival for all RCC patients was 13.2 months. CONCLUSION: Pegylated IFNalpha-2b
      was active and well tolerated in patients with metastatic solid tumors, including
      RCC, at doses up to 6.0 micro g/kg/wk.

PMID- 12228204
TI  - Lack of expression of galectin-3 is associated with a poor outcome in node
      negative patients with laryngeal squamous-cell carcinoma.
AB  - PURPOSE: Galectin-3 is a pleiotropic carbohydrate-binding protein participating
      in a variety of normal and pathologic processes, including cancer progression.
      This study was aimed at evaluating the prognostic value of galectin-3 expression
      in node-negative laryngeal squamous-cell carcinoma (SCC). PATIENTS AND METHODS:
      Galectin-3 expression was analyzed by immunohistochemistry using M3/38 monoclonal
      antibody, in a single-institution series of 73 node-negative laryngeal SCC
      patients (median follow-up, 52 months; range, 2 to 90 months). RESULTS: Forty-two
      (57.5%) of 73 patients expressed galectin-3. Galectin-3 expression was positively
      associated with tumor keratinization and histologic grade. A significant
      correlation was found between galectin-3 tumor positivity and longer relapse-free
      and overall survival. In univariate analysis, high-grade (grade 3 or 4) tumors,
      nonkeratinizing tumors, and galectin-3-negative tumors showed a significantly
      increased risk of relapse and death. In multivariate analysis, only galectin-3
      expression retained an independent prognostic significance for both relapse-free
      and overall survival. CONCLUSION: We conclude that the absence of galectin-3
      expression is an independent negative prognostic marker in laryngeal SCC
      patients. Thus, histochemical detection of galectin-3 in these tumors could be
      useful for the selection of node-negative patients with potentially unfavorable
      outcomes, to establish adjuvant therapy protocols.

PMID- 12228205
TI  - Phase II multicenter trial of a weekly paclitaxel and carboplatin regimen in
      patients with advanced breast cancer.
AB  - PURPOSE: To determine the activity of weekly paclitaxel plus carboplatin as first
      line therapy in patients with advanced breast cancer (ABC) by assessing response
      rate, survival, and safety. PATIENTS AND METHODS: One hundred patients with ABC
      received paclitaxel 135 mg/m(2) (group 1, n = 20) and carboplatin area under the
      concentration-time curve (AUC) of 2. Paclitaxel was subsequently reduced to 100
      mg/m(2) (group 2, n = 80) because of toxicity. The median age was 58.5 years, and
      most patients had an Eastern Cooperative Oncology Group performance status of
      <or= 2. Estrogen and progesterone receptor status were evenly distributed among
      both groups. Sixty-one patients received prior chemotherapy, 37 (61%) of whom
      received prior doxorubicin. Among 47 patients who received prior hormonal
      therapy, 43 received tamoxifen. RESULTS: The overall response rate (ORR) among 95
      assessable patients was 62%, including 8% complete responses and 54% partial
      responses. The median time to response was 1.8 months, and the median duration of
      response was 13.3 months. The median time to progression was 4.8 months. The
      median survival was 16 months. Neutropenia and leukopenia were the most common
      grade 3 and 4 toxicities. In group 1, neutropenia (50%) and leukopenia (35%)
      necessitated dose reductions for 50% of patients during the first three cycles,
      prompting the reduction in paclitaxel dose to 100 mg/m(2). Grade 3 and 4
      nonhematologic toxicities for all patients included peripheral neuropathy (11%),
      infection (6%), anemia (5%), weakness (6%), and paresthesia (3%). CONCLUSION: The
      62% ORR achieved with weekly paclitaxel plus carboplatin is among the highest
      achieved with chemotherapy for ABC. This high response rate and the lack of
      cardiotoxicity suggest that the regimen should be considered as a
      nonanthracycline regimen for future adjuvant therapy.

PMID- 12228206
TI  - Clinical significance of p21 expression in non-small-cell lung cancer.
AB  - PURPOSE: The clinical significance of p21 expression remains unclear, whereas
      many experimental studies have demonstrated that p21, the product of the
      WAF1/CIP1/SDI1 gene, plays an important role in regulation of the cell cycle as
      an inhibitor of cyclin-dependent kinases. The purpose of this study was to
      clarify the clinical significance in resected non-small-cell lung cancer (NSCLC).
      PATIENTS AND METHODS: A total of 233 consecutive patients with completely
      resected pathologic stage I to IIIA NSCLC were retrospectively reviewed.
      Expression of p21 and the status of p53 were examined immunohistochemically.
      Proliferative activity was also evaluated immunohistochemically. The incidence of
      apoptotic cell death was evaluated by terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate-biotin nick end-labeling staining. RESULTS:
      Expression of p21 was positive in 120 patients (51.5%). The 5-year survival rate
      of p21-positive patients was 73.8%, significantly higher than that of p21
      negative patients (60.7%; P =.006). Aberrant expression of p53 was positive in 98
      patients (42.1%). When combined with p53 status, the prognostic value of p21
      status was enhanced: the 5-year survival rate of p21-positive and p53-negative
      patients was 80.7%, markedly higher than that of p21-negative and p53-positive
      patients (50.0% for both; P =.001). Multivariate analysis confirmed that positive
      expression of p21 was a significant factor for predicting a favorable prognosis.
      There was no significant correlation between p21 expression and p53 status,
      proliferative activity, or incidence of apoptosis. CONCLUSION: p21 expression was
      shown to be an independent prognostic factor in NSCLC.

PMID- 12228207
TI  - Treatment of extranodal marginal zone B-cell lymphoma of mucosa-associated
      lymphoid tissue type with cladribine: a phase II study.
AB  - PURPOSE: As chemotherapy has not been extensively studied in patients with
      lymphoma of the mucosa-associated lymphoid tissue (MALT), we initiated a
      prospective study to evaluate the activity of the nucleoside analog cladribine (2
      chlorodeoxyadenosine [2-CdA]) in this disease. PATIENTS AND METHODS: Patients
      with histologically verified MALT-type lymphoma were enrolled. 2-CdA was
      administered at a dose of 0.12 mg/kg body weight on 5 consecutive days, as a 2
      hour infusion. Cycles were repeated every 4 weeks for a maximum of six cycles.
      RESULTS: Nineteen patients with gastric and seven patients with extragastric MALT
      lymphoma were enrolled. All patients were chemotherapy-naive, and two had been
      locally irradiated before systemic relapse of the lymphoma. A total of 102 cycles
      was administered to our patients (median number of cycles per patient, four). All
      25 assessable patients responded to treatment: 21 patients (84%) achieved
      complete remission (CR) and four patients achieved partial remission. All
      patients (100%) with gastric presentation, but only three patients (43%) with
      extragastric presentation, achieved CR. Toxicities were moderate and mainly
      hematologic and required dose reduction and/or premature discontinuation of
      therapy in only three cases. Two patients died from vascular events, one shortly
      after the first cycle because of myocardial infarction and the other from stroke
      3 months after the second course. Three patients relapsed after 13, 18, and 22
      months and one patient showed progressive disease after 15 months. At present, 24
      patients are alive at a median follow-up time of 32 months. CONCLUSION: Our data
      demonstrate that 2-CdA is highly effective in inducing CR in 84% of patients with
      MALT-type lymphoma.

PMID- 12228208
TI  - Therapy-related myeloid leukemias are observed in patients with chronic
      lymphocytic leukemia after treatment with fludarabine and chlorambucil: results
      of an intergroup study, cancer and leukemia group B 9011.
AB  - PURPOSE: Patients with chronic lymphocytic leukemia (CLL) may have disease
      transformation to non-Hodgkin's lymphoma or prolymphocytic leukemia; however,
      development of therapy-related acute myeloid leukemia (t-AML) is unusual. A
      series of patients enrolled onto an intergroup CLL trial were examined for this
      complication. PATIENTS AND METHODS: A total of 544 previously untreated B-cell
      CLL patients were enrolled onto a randomized intergroup study comparing treatment
      with chlorambucil, fludarabine, or fludarabine plus chlorambucil. Case report
      forms from 521 patients were reviewed for t-AML. RESULTS: With a median follow-up
      of 4.2 years, six patients (1.2%) to date have developed therapy-related
      myelodysplastic syndrome (t-MDS; n = 3), t-AML (n = 2), or t-MDS evolving to t
      AML (n = 1), from 27 to 53 months (median, 34 months) after study entry. This
      included five (3.5%) of 142 patients treated with fludarabine plus chlorambucil
      and one (0.5%) of 188 receiving fludarabine; no chlorambucil-treated patients
      developed t-MDS or t-AML (P =.007). At study entry, the median age among these
      six patients was 56 years (range, 44 to 72 years); three were male; the CLL Rai
      stage was I/II (n = 4) or III/IV (n = 2). Response to CLL therapy was complete (n
      = 4) or partial remission (n = 1) and stable disease (n = 1). Marrow
      cytogenetics, obtained in three of six cases at diagnosis of t-MDS or t-AML, were
      complex, with abnormalities in either or both chromosomes 5 and 7. Other
      abnormalities involved chromosomes X, 1, 8, 12, 17, and 19. Median survival after
      diagnosis of t-MDS/AML was 3.5 months (range, 0.5 to 10.1 months). CONCLUSION:
      Our findings raise the possibility that alkylator-purine analog combination
      therapy may increase the risk of therapy-related myeloid malignancies, which is
      of particular relevance with regard to ongoing trials using these combination
      therapies.

PMID- 12228209
TI  - Subsequent chemotherapy regimens are well tolerated after radioimmunotherapy with
      yttrium-90 ibritumomab tiuxetan for non-Hodgkin's lymphoma.
AB  - PURPOSE: Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin; IDEC Pharmaceutical, San
      Diego, CA) is an effective therapy for patients with relapsed B-cell non
      Hodgkin's lymphoma. The predominant toxicity of 90Y ibritumomab tiuxetan has been
      myelosuppression, and concern has been expressed about the tolerability of
      further treatment after this therapy. The goal of this analysis was to evaluate
      the therapy given to patients who relapsed after 90Y ibritumomab tiuxetan.
      PATIENTS AND METHODS: A retrospective analysis was performed on 58 patients
      treated at a single institution on five separate protocols that used 90Y
      ibritumomab tiuxetan 0.4 mCi/kg. All patients had experienced disease progression
      after 90Y ibritumomab tiuxetan treatment and received subsequent therapy. The
      toxicity seen in this cohort of patients with subsequent treatment regimens was
      analyzed and compared with that of control groups who did not receive 90Y
      ibritumomab tiuxetan. RESULTS: The median number of subsequent therapies was two
      (range, one to seven). Sixteen (28%) of the 58 patients received growth factor
      support with subsequent chemotherapy, and two patients were treated with reduced
      doses because of persistent pancytopenia. Eight patients subsequently had an
      autologous stem-cell transplantation with stem cells collected after 90Y
      ibritumomab tiuxetan therapy. Excluding patients hospitalized at the time of
      transplantation, 13 patients were hospitalized for neutropenic fever,
      thrombocytopenia, or both. When compared to patients who did not receive 90Y
      ibritumomab tiuxetan, there was no significant difference in toxicity.
      CONCLUSION: We conclude that chemotherapy or autologous stem-cell transplantation
      after prior therapy with 90Y ibritumomab tiuxetan is feasible and reasonably well
      tolerated. The toxicity with subsequent therapy seems similar to that in patients
      not treated with 90Y ibritumomab tiuxetan.

PMID- 12228210
TI  - Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also
      had received fludarabine.
AB  - PURPOSE: This phase II pilot study determined the efficacy and safety of
      alemtuzumab (Campath-1H; Burroughs Wellcome, United Kingdom) in patients with
      chronic lymphocytic leukemia (CLL), all of whom had previously received
      fludarabine and other chemotherapy regimens. PATIENTS AND METHODS: Twenty-four
      patients were treated with intravenous alemtuzumab at six centers in the United
      States. The target dose of 30 mg over 2 hours, three times weekly, was
      administered for up to 16 weeks. Responses were evaluated by an independent panel
      of experts using 1996 National Cancer Institute-sponsored Working Group criteria.
      Safety assessments included analysis of lymphocyte subpopulations. Antimicrobial
      prophylaxis was not mandatory. RESULTS: Eight patients (33%) achieved a major
      response (all partial remissions), with a median time to response of 3.9 months
      (range, 1.6 to 5.3 months). The median duration of response was 15.4 months
      (range, 4.6 to >or= 38.0 months), the median time to disease progression was 19.6
      months (range, 7.7 to >or= 42.0 months), and the median survival time was 35.8
      months (range, 8.8 to >or= 47.1 months). Acute infusion-related events, mainly
      grades 1 and 2, were most common and most severe in the first week. Ten patients
      (eight nonresponders and two responders) experienced major infections on-study.
      Pneumocystis carinii pneumonia was reported in two patients on-study; neither had
      received prophylaxis. Median CD4+ and CD8+ counts decreased and then began to
      increase by the end of the study, with further recovery by 1-month follow-up. One
      of 53 samples obtained from 10 patients had a low titer of alemtuzumab
      antibodies. CONCLUSION: Alemtuzumab has significant activity in poor-prognosis,
      fludarabine-treated CLL patients. However, because of a relatively high incidence
      of opportunistic infections accompanying profound lymphopenia, future protocols
      should include mandatory prophylaxis.

PMID- 12228211
TI  - Prognostic value of KIT mutation type, mitotic activity, and histologic subtype
      in gastrointestinal stromal tumors.
AB  - PURPOSE: Previous studies have reported clinical correlates for KIT mutations in
      GISTs, but in most of those studies the KIT mutations were found in less than 50%
      of the GISTs. The aim of this study was to evaluate the prognostic relevance for
      KIT mutations in a series of GISTs in which the mutations were evaluated
      intensively by genomic and cDNA sequencing. PATIENTS AND METHODS: A comprehensive
      clinical and pathologic analysis of 48 patients with GISTs who had snap-frozen
      tissue was performed. The median tumor size was 10 cm (range, 2 to 30 cm). Median
      follow-up for disease-free patients was 48 months. KIT genomic and cDNA was
      sequenced by using nucleic acid templates isolated from frozen tumors. RESULTS:
      The overall 5-year recurrence-free survival was 41% +/- 6%. Five-year recurrence
      free survival for patients with tumors that had mitotic counts of three mitoses
      or fewer per 30 high-power fields (HPF), more than three to <or= 15 mitoses per
      30 HPF, and more than 15 mitoses per 30 HPF were 89% +/- 7%, 49% +/- 12%, and 16%
      +/- 6%, respectively (P =.0001). The 32 patients with spindle-cell histology had
      a 49% +/- 7% 5-year recurrence-free survival; in contrast, the 16 patients with
      epithelioid or mixed histology had a 23% +/- 11% 5-year recurrence-free survival
      (P =.01). Five-year recurrence-free survival for patients with tumors less than 5
      cm, 5 to 10 cm, and more than 10 cm were 82% +/- 12%, 45% +/- 9%, and 27% +/- 8%,
      respectively (P =.03). Prognostic associations were found with particular KIT
      mutation types, and patients with missense exon 11 mutations had a 5-year
      recurrence-free survival of 89% +/- 11% compared with 40% +/- 8% for GISTs with
      other mutation types (P =.03). The independent predictors for disease-free
      survival were the presence of deletion/insertion exon 11 mutations (hazard ratio
      [HR] = 4; P =.006), more than 15 mitoses per 30 HPF (HR = 18; P =.0001), mixed
      histology (HR = 21; P =.0001), and male sex (HR = 3; P =.05). CONCLUSION: In this
      series of KIT-expressing GISTs, tumor mitotic activity and histologic subtype
      were the most important prognostic features. The majority of GISTs contain KIT
      activating mutations with the type/location of mutation serving as an independent
      predictor for disease-free survival. These results suggest that KIT mutation and
      activation are important in GIST pathogenesis and also may provide important
      prognostic information.

PMID- 12228212
TI  - Mechanisms and future directions for angiogenesis-based cancer therapies.
AB  - Targeting angiogenesis represents a new strategy for the development of
      anticancer therapies. New targets derived from proliferating endothelial cells
      may be useful in developing anticancer drugs that prolong or stabilize the
      progression of tumors with minimal systemic toxicities. These drugs may also be
      used as novel imaging and radiommunotherapeutic agents in cancer therapy. In this
      review, the mechanisms and control of angiogenesis are discussed. Genetic and
      proteomic approaches to defining new potential targets on tumor vasculature are
      then summarized, followed by discussion of possible antiangiogenic treatments
      that may be derived from these targets and current clinical trials. Such
      strategies involve the use of endogenous antiangiogenic agents, chemotherapy,
      gene therapy, antiangiogenic radioligands, immunotherapy, and endothelial cell
      based therapies. The potential biologic end points, toxicities, and resistance
      mechanisms to antiangiogenic agents must be considered as these therapies enter
      clinical trials.

PMID- 12228213
TI  - p53 and MDM2 in germ cell cancer treatment response.

PMID- 12228214
TI  - Adjuvant radiation for stage IIb soft tissue sarcoma of the extremity.

PMID- 12228216
TI  - Screening for lung cancer.

PMID- 12228215
TI  - Colostomies may influence patient quality of life more than poor sphincter
      function.

PMID- 12228217
TI  - Ethical issues surrounding the conduct of off-shore clinical research.

PMID- 12228218
TI  - Nonovarian pelvic cancers in BRCA1/2 mutation carriers and the BRCAPRO
      statistical model.

PMID- 12228219
TI  - Chronomodulated chemotherapy in advanced colorectal carcinoma.

PMID- 12228220
TI  - SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of
      IRS1 and IRS2.
AB  - Inflammation associates with peripheral insulin resistance, which dysregulates
      nutrient homeostasis and leads to diabetes. Inflammation induces the expression
      of SOCS proteins. We show that SOCS1 or SOCS3 targeted IRS1 and IRS2, two
      critical signaling molecules for insulin action, for ubiquitin-mediated
      degradation. SOCS1 or SOCS3 bound both recombinant and endogenous IRS1 and IRS2
      and promoted their ubiquitination and subsequent degradation in multiple cell
      types. Mutations in the conserved SOCS box of SOCS1 abrogated its interaction
      with the elongin BC ubiquitin-ligase complex without affecting its binding to
      IRS1 or IRS2. The SOCS1 mutants also failed to promote the ubiquitination and
      degradation of either IRS1 or IRS2. Adenoviral-mediated expression of SOCS1 in
      mouse liver dramatically reduced hepatic IRS1 and IRS2 protein levels and caused
      glucose intolerance; by contrast, expression of the SOCS1 mutants had no effect.
      Thus, SOCS-mediated degradation of IRS proteins, presumably via the elongin BC
      ubiquitin-ligase, might be a general mechanism of inflammation-induced insulin
      resistance, providing a target for therapy.

PMID- 12228221
TI  - Manganese stimulation and stereospecificity of the Dopa (3,4
      dihydroxyphenylalanine)/tyrosine-sulfating activity of human monoamine-form
      phenol sulfotransferase. Kinetic studies of the mechanism using wild-type and
      mutant enzymes.
AB  - Kinetic studies were performed to dissect the mechanism underlying the remarkable
      Mn(2+) stimulation of the Dopa/tyrosine-sulfating activity of the human monoamine
      (M)-form phenol sulfotransferase (PST). The activities and the stimulation by
      Mn(2+) are highly stereospecific for the d-form enantiomers of tyrosine and Dopa.
      Analysis of the kinetic results strongly suggests that tyrosine-Mn(2+) and
      tyrosine-Mn(2+)-tyrosine complexes are obligatory substrates, whereas Dopa-Mn(2+)
      complexes may be better substrates than Dopa alone. This activation of the
      Dopa/tyrosine-sulfating activity of M-form PST by Mn(2+) via complex formation
      between Mn(2+) and the substrate is the first reported case of a regulatory
      mechanism in this important class of enzymes. Our previous studies using point
      mutated M-form PSTs established that the Mn(2+) (in the substrate-Mn(2+) complex)
      exerts its stimulatory effect by binding predominantly to the Asp-86 residue at
      the active site. We present here further studies using dopamine as substrate to
      bolster this conclusion. The possible physiological implications of this rather
      unusual specificity for the d-amino acid and its derivatives and the stimulation
      by Mn(2+) are discussed in the context of protective and detoxification
      mechanisms that may operate in neurodegenerative processes in the brain. The
      Mn(2+) stimulation of the activity of M-form PST toward d-enantiomers of
      Dopa/tyrosine may have implications for other substrates (including chiral drugs)
      and for the other cytosolic sulfotransferases that are involved in the regulation
      of endogenous metabolites as well as in detoxification.

PMID- 12228222
TI  - Activation of pyk2/related focal adhesion tyrosine kinase and focal adhesion
      kinase in cardiac remodeling.
AB  - Cellular remodeling during progression of dilation involves focal adhesion
      contact reorganization. However, the signaling mechanisms and structural
      consequences leading to impaired cardiomyocyte adhesion are poorly defined. These
      events were studied in tropomodulin-overexpressing transgenic mice that develop
      dilated cardiomyopathy associated with chronic elevation of intracellular
      calcium. Analysis of tropomodulin-overexpressing transgenic hearts by immunoblot
      and confocal microscopy revealed activation and redistribution of signaling
      molecules known to regulate adhesion. Calcium-dependent pyk2/related focal
      adhesion tyrosine kinase (RAFTK) showed changes in expression and phosphorylation
      state, similar to changes observed for a related downstream target molecule of
      pyk2/RAFTK termed focal adhesion kinase. Paxillin, the target substrate molecule
      for focal adhesion kinase phosphorylation, was redistributed in tropomodulin
      overexpressing transgenic hearts with enhanced paxillin phosphorylation and
      cleavage. Certain aspects of the in vivo signaling phenotype including increased
      paxillin phosphorylation could be recapitulated in vitro using neonatal rat
      cardiomyocytes infected with recombinant adenovirus to overexpress tropomodulin.
      In addition, increasing intracellular calcium levels with ionomycin induced
      pyk2/RAFTK phosphorylation, and adenovirally mediated expression of wild-type
      pyk2/RAFTK resulted in increased phospho-pyk2/RAFTK levels and concomitant
      paxillin phosphorylation. Collectively, these results delineate a cardiomyocyte
      signaling pathway associated with dilation that has potential relevance for
      cardiac remodeling, focal adhesion reorganization, and loss of contractility.

PMID- 12228223
TI  - Suprabasin, a novel epidermal differentiation marker and potential cornified
      envelope precursor.
AB  - The suprabasin gene is a novel gene expressed in mouse and human differentiating
      keratinocytes. We identified a partial cDNA encoding suprabasin using a
      suppression subtractive hybridization method between the proliferative basal and
      differentiating suprabasal populations of the mouse epidermis. A 3' gene-specific
      probe hybridized to transcripts of 0.7- and 2.2-kb pairs on Northern blots with
      specific detection in differentiated keratinocytes of stratified epithelia. The
      mouse gene was mapped to chromosome 7 by fluorescence in situ hybridization. This
      region is syntenic to human chromosome band 19q13.1, which contained the only
      region in the data bases with homology to the mouse suprabasin sequence. During
      embryonic mouse development, suprabasin mRNA was detected at day 15.5, coinciding
      with epidermal stratification. Suprabasin was detected in the suprabasal layers
      of the epithelia in the tongue, stomach, and epidermis. Differentiation of
      cultured primary epidermal keratinocytes with 0.12 mm Ca(2+) or 12-O
      tetradecanoylphorbol-13-acetate treatment resulted in the induction of
      suprabasin. The 2.2-kb cDNA transcript encodes a protein of 72 kDa with a
      predicted isoelectric point of 6.85. The translated sequence has an amino
      terminal domain, a central domain composed of repeats rich in glycine and
      alanine, and a carboxyl-terminal domain. The alternatively spliced 0.7-kb
      transcript encodes a smaller protein that shares the NH(2)- and COOH-terminal
      regions but lacks the repeat domain region. Cross-linking experiments indicate
      that suprabasin is a substrate for transglutaminase 2 and 3 activity. Altogether,
      these results indicate that the suprabasin protein potentially plays a role in
      the process of epidermal differentiation.

PMID- 12228224
TI  - Central role of glycogen synthase kinase-3beta in endoplasmic reticulum stress
      induced caspase-3 activation.
AB  - Stress of the endoplasmic reticulum (ER), which is associated with many
      neurodegenerative conditions, can lead to the elimination of affected cells by
      apoptosis through only partially understood mechanisms. Thapsigargin, which
      causes ER stress by inhibiting the ER Ca(2+)-ATPase, was found to not only
      activate the apoptosis effector caspase-3 but also to cause a large and prolonged
      increase in the activity of glycogen synthase kinase-3beta (GSK3beta). Activation
      of GSK3beta was obligatory for thapsigargin-induced activation of caspase-3,
      because inhibition of GSK3beta by expression of dominant-negative GSK3beta or by
      the GSK3beta inhibitor lithium blocked caspase-3 activation. Thapsigargin
      treatment activated GSK3beta by inducing dephosphorylation of phospho-Ser-9 of
      GSK3beta, a phosphorylation that normally maintains GSK3beta inactivated. Caspase
      3 activation induced by thapsigargin was blocked by increasing the
      phosphorylation of Ser-9-GSK3beta with insulin-like growth factor-1 or with the
      phosphatase inhibitors okadaic acid and calyculin A, but the calcineurin
      inhibitors FK506 and cyclosporin A were ineffective. Insulin-like growth factor
      1, okadaic acid, calyculin A, and lithium also protected cells from two other
      inducers of ER stress, tunicamycin and brefeldin A. Thus, ER stress activates
      GSK3beta through dephosphorylation of phospho-Ser-9, a prerequisite for caspase-3
      activation, and this process is amenable to pharmacological intervention.

PMID- 12228225
TI  - Lesion bypass activities of human DNA polymerase mu.
AB  - DNA polymerase mu (Polmu) is a newly discovered member of the polymerase X family
      with unknown cellular function. The understanding of Polmu function should be
      facilitated by an understanding of its biochemical activities. By using purified
      human Polmu for biochemical analyses, we discovered the lesion bypass activities
      of this polymerase in response to several types of DNA damage. When it
      encountered a template 8-oxoguanine, abasic site, or 1,N(6)-ethenoadenine,
      purified human Polmu efficiently bypassed the lesion. Even bulky DNA adducts such
      as N-2-acetylaminofluorene-adducted guanine, (+)- and (-)-trans-anti
      benzo[a]pyrene-N(2)-dG were unable to block the polymerase activity of human
      Polmu. Bypass of these simple base damage and bulky adducts was predominantly
      achieved by human Polmu through a deletion mechanism. The Polmu specificity of
      nucleotide incorporation indicates that the deletion resulted from primer
      realignment before translesion synthesis. Purified human Polmu also effectively
      bypassed a template cis-syn TT dimer. However, this bypass was achieved in a
      mainly error-free manner with AA incorporation opposite the TT dimer. These
      results provide new insights into the biochemistry of human Polmu and show that
      efficient translesion synthesis activity is not strictly confined to the Y family
      polymerases.

PMID- 12228226
TI  - A seed-specific heat-shock transcription factor involved in developmental
      regulation during embryogenesis in sunflower.
AB  - We report the cloning and functional characterization of the first heat-shock
      transcription factor that is specifically expressed during embryogenesis in the
      absence of environmental stress. In sunflower embryos this factor, HaHSFA9, trans
      activated promoters with poor consensus heat-shock cis-elements, including that
      of the seed-specific Hahsp17.6G1 gene. Mutations that improved the heat-shock cis
      element consensus at the Hahsp17.7G4 promoter impaired transient activation by
      HaHSFA9 in sunflower embryos. The same mutations did not affect heat-shock
      induced gene expression of this promoter in transgenic tobacco plants but reduced
      the developmental activation by endogenous heat-shock transcription factors
      (HSFs) in seeds. Sunflower, and perhaps other plants such as tobacco, differs
      from the vertebrate animal systems in having at least one specialized HSF with
      expression and (or) activation patterns strictly restricted to embryos. Our
      results strongly indicate that HaHSFA9 is a transcription factor critically
      involved in the developmental activation of Hahsp17.6G1 and in that of similar
      target genes as Hahsp17.7G4.

PMID- 12228227
TI  - Docking of HIV-1 Vpr to the nuclear envelope is mediated by the interaction with
      the nucleoporin hCG1.
AB  - The HIV-1 genome contains several genes coding for auxiliary proteins, including
      the small Vpr protein. Vpr affects the integrity of the nuclear envelope and
      participates in the nuclear translocation of the preintegration complex
      containing the viral DNA. Here, we show by photobleaching experiments performed
      on living cells expressing a Vpr-green fluorescent protein fusion that the
      protein shuttles between the nucleus and the cytoplasm, but a significant
      fraction is concentrated at the nuclear envelope, supporting the hypothesis that
      Vpr interacts with components of the nuclear pore complex. An interaction between
      HIV-1 Vpr and the human nucleoporin CG1 (hCG1) was revealed in the yeast two
      hybrid system, and then confirmed both in vitro and in transfected cells. This
      interaction does not involve the FG repeat domain of hCG1 but rather the N
      terminal region of the protein. Using a nuclear import assay based on digitonin
      permeabilized cells, we demonstrate that hCG1 participates in the docking of Vpr
      at the nuclear envelope. This association of Vpr with a component of the nuclear
      pore complex may contribute to the disruption of the nuclear envelope and to the
      nuclear import of the viral DNA.

PMID- 12228228
TI  - Binding of JNK/SAPK to MEKK1 is regulated by phosphorylation.
AB  - We sought to characterize the role of upstream kinases in the regulation of the
      MAP3 kinase MEKK1 and the potential impact on signaling to MAP kinase cascades.
      We find that the MAP4 kinase PAK1 phosphorylates the amino terminus of MEKK1 on
      serine 67. We show that serine 67 lies in a D domain, which binds to the c-Jun
      NH(2)-terminal kinase/stress-activated protein kinases (JNK/SAPK). Serine 67 is
      constitutively phosphorylated in resting 293 cells, but is dephosphorylated
      following exposure to stress stimuli such as anisomycin and UV irradiation.
      Phosphorylation of this site inhibits binding of JNK/SAPK to MEKK1. Thus, we
      propose a mechanism by which the MEKK1-dependent JNK/SAPK pathway is negatively
      regulated by PAK through phosphorylation of serine 67.

PMID- 12228229
TI  - Alphavirus 6K proteins form ion channels.
AB  - Ross River virus and Barmah Forest virus are Australian arboviruses of the
      Alphavirus genus. Features of alphavirus infection include an increased
      permeability of cells to monovalent cations followed by virion budding. Virally
      encoded ion channels are thought to have a role in these processes. In this
      paper, the 6K proteins of Ross River virus and Barmah Forest virus are shown to
      form cation-selective ion channels in planar lipid bilayers. Using a novel
      purification method, bacterially expressed 6K proteins were inserted into
      bilayers with a defined orientation (i.e. N-terminal cis, C-terminal trans).
      Channel activity was reversibly inhibited by antibodies to the N and C termini of
      6K protein added to the cis and trans baths, respectively. Channel conductances
      varied from 40-800 picosiemens, suggesting that the protein is able to form
      channels with a range of possible oligomerization states.

PMID- 12228230
TI  - Structural determinants for the biological activity of Vav proteins.
AB  - We have used an extensive mutagenesis approach to study the specific role of the
      eight structural domains of Vav during both the activation and signaling steps of
      this Rac1 exchange factor. Our results indicate that several Vav domains (Dbl
      homology, pleckstrin homology, and zinc finger) are essential for all the
      biological activities tested, whereas others are required for discrete, cell type
      specific biological effects. Interestingly, we have found that Vav domains have
      no unique functions. Thus, the calponin homology domain mediates the inhibition
      of Vav both in vitro and in vivo but, at the same time, exerts effector functions
      in lymphocytes upon receptor activation. The Vav SH2 and SH3 regions play
      regulatory roles in the activation of Vav in fibroblasts, mediating both its
      phosphorylation and translocation to the plasma membrane. In contrast, the Vav
      SH2 and SH3 regions act as scaffolding platforms in T-cells, ensuring the proper
      phosphorylation of Vav and the subsequent engagement of downstream effectors. We
      also provide evidence indicating that the zinc finger region exerts at least
      three different functional roles in Vav, aiding in the down-regulation of its
      basal activity, the engagement of substrates, and the induction of ancillary
      pathways required for cell transformation. Finally, the results obtained are
      consistent with a new regulatory model for Vav, in which the calponin homology
      region inhibits the basal activity of Vav through interactions with the zinc
      finger region.

PMID- 12228231
TI  - Phosphorylation of serine 256 suppresses transactivation by FKHR (FOXO1) by
      multiple mechanisms. Direct and indirect effects on nuclear/cytoplasmic shuttling
      and DNA binding.
AB  - FKHR is a member of the FOXO subfamily of Forkhead transcription factors, which
      are important targets for insulin and growth factor signaling. FKHR contains
      three predicted protein kinase B phosphorylation sites (Thr-24, Ser-256, and Ser
      319) that are conserved in other FOXO proteins. We have reported that
      phosphorylation of Ser-256 is critical for the ability of insulin and insulin
      like growth factors to suppress transactivation by FKHR (Guo, S., Rena, G.,
      Cichy, S., He, X., Cohen, P., and Unterman, T. (1999) J. Biol. Chem. 274, 17184
      17192) and for its exclusion from the nucleus (Rena, G., Prescott, A. R., Guo,
      S., Cohen, P., and Unterman, T. G. (2001) Biochem. J. 354, 605-612). Ser-256 is
      located in a basic region of the FKHR DNA binding domain where phosphorylation
      may have direct effects on DNA binding and/or nuclear targeting. Phosphorylation
      of Ser-256 may also be required for the phosphorylation of Thr-24 and Ser-319.
      Here, we provide the first direct evidence that basic residues in the FKHR DNA
      binding domain are critical for DNA binding and that Ser-256 phosphorylation
      alters binding activity. Ser-256 phosphorylation also is critical for regulating
      nuclear/cytoplasmic trafficking; however, this effect requires Thr-24/Ser-319
      phosphorylation. Transient transfection studies with reporter gene constructs in
      293 cells reveal that the phosphorylation of Ser-256 can inhibit the function of
      FKHR independent of Thr-24/Ser-319 phosphorylation. Studies with GFP(1) fusion
      proteins indicate that Ser-256 phosphorylation is critical for nuclear exclusion
      of FKHR. However, this effect is disrupted when Thr-24 and Ser-319 are replaced
      by alanine, indicating that nuclear exclusion of FKHR also requires Thr-24/Ser
      319 phosphorylation. Gel shift and fluorescence anisotropy studies reveal that
      basic residues at the C-terminal end of the FKHR DBD are important for DNA
      binding, and the introduction of a negative charge at the site of Ser-256 limits
      binding activity. Binding is rapid and reversible, providing an opportunity for
      the phosphorylation of Ser-256 and subsequent phosphorylation of Thr-24 and Ser
      319 and nuclear exclusion of FKHR.

PMID- 12228232
TI  - Regulation of 3' splice site selection in the 844ins68 polymorphism of the
      cystathionine Beta -synthase gene.
AB  - 844ins68 is a frequent polymorphism of the cystathionine beta-synthase gene (CBS)
      that consists of a 68-bp insertion duplicating the 3' splice site of intron 7 and
      the 5'-end of exon 8. The presence of two identical 3' splice sites spaced by 68
      bp should lead to either a selection of the proximal site or to at least two
      alternatively spliced CBS mRNA variants. Instead, an accurate selection of the
      distal 3' splice site is observed in the 844ins68 carriers. The duplication has
      generated a gene re-arrangement at the 3' splice site where two GGGG runs have
      been brought close to each other. Using a minigene system, we have investigated
      the effect this peculiar configuration might have on the selection of the 3'
      splice site of intron 7 in the CBS gene. Minimal disruption of the G runs
      resulted in a dramatic shift toward the proximal 3' splice site selection with
      inclusion of the 68-bp insertion and a consequent change of the reading frame.
      The insertional event created this peculiar configuration of two G repeats close
      to each other that subsequently acquired the ability to strongly bind
      heterogeneous nuclear ribonucleoprotein (hnRNP) H1, a specific trans-acting
      factor. The interaction of hnRNP H1 with G runs within the 844ins68 context might
      interfere with the recruitment of splicing factors to the proximal 3' splice site
      thus favoring the selection of the distal 3' splice site. Our results therefore
      suggest the possibility that the insertion was an evolutionary event that allowed
      the rescue of the wild-type sequence, so preserving protein function.

PMID- 12228233
TI  - Processing of beta-amyloid precursor-like protein-1 and -2 by gamma-secretase
      regulates transcription.
AB  - The familial Alzheimer's disease gene product beta-amyloid (Abeta) precursor
      protein (APP) is processed by the beta- and gamma-secretases to produce Abeta as
      well as AID (APP Intracellular Domain) which is derived from the extreme carboxyl
      terminus of APP. AID was originally shown to lower the cellular threshold to
      apoptosis and more recently has been shown to modulate gene expression such that
      it represses Notch-dependent gene expression while in combination with Fe65 it
      enhances gene activation. Here we report that the two other members of the APP
      family, beta-amyloid precursor-like protein-1 and -2 (APLP1 and APLP2), are also
      processed by the gamma-secretase in a Presenilin 1-dependent manner. Furthermore,
      the extreme carboxyl-terminal fragments produced by this processing (here termed
      APP-like Intracellular Domain or ALID1 and ALID2) are able to enhance Fe65
      dependent gene activation, similar to what has been reported for AID. Considering
      that only APP and not the APLPs have been linked to familial Alzheimer's disease
      (AD), this data should help in understanding the physiologic roles of the APP
      family members and in differentiating these functions from the pathologic role of
      APP in Alzheimer's disease.

PMID- 12228234
TI  - The human reduced folate carrier gene is regulated by the AP2 and sp1
      transcription factor families and a functional 61-base pair polymorphism.
AB  - Recently, our laboratory reported an intricate regulation of the human reduced
      folate carrier (hRFC) gene, involving multiple promoters and noncoding exons. We
      localized promoter activity to a 452-bp GC-rich region upstream of noncoding exon
      A, including a 47-bp basal promoter with a CRE/AP-1-like consensus element that
      bound the bZip family of DNA-binding proteins (e.g. CREB-1 and c-Jun). We now
      report that three nearly identical tandem repeats (49-61 bp) in the hRFC-A
      upstream region are involved in regulating promoter activity. By in vitro binding
      assays, multiple transcription factors (e.g. AP2 and Sp1/Sp3) bound this region.
      When AP2 was cotransfected with the hRFC-A reporter construct into HT1080 cells,
      promoter activity increased 3-fold. In Drosophila SL2 cells, Sp1 transactivated
      promoter A and showed synergism with CREB-1. However, c-Jun was antagonistic to
      the effects of Sp1. A sequence variant in the hRFC-A repeated region was
      identified, involving an exact duplication of a 61-bp sequence. This variant had
      an allelic frequency of 78% in 72 genomic DNAs and resulted in a 63% increase in
      promoter activity. These results identify important regions in the hRFC-A
      promoter and critical roles for AP2 and Sp1, in combination with the bZip
      transcription factors. Moreover, they document a functionally novel polymorphism
      that increases promoter activity and may contribute to interpatient variations in
      hRFC expression and effects on tissue folate homeostasis and antitumor response
      to antifolates.

PMID- 12228235
TI  - Prevalent involvement of illegitimate V(D)J recombination in chromosome 9p21
      deletions in lymphoid leukemia.
AB  - To understand molecular pathways underlying 9p21 deletions, which lead to
      inactivation of the p16/CDKN2A, p14/ARF, and/or p15/CDKN2B genes, in lymphoid
      leukemia, 30 breakpoints were cloned from 15 lymphoid leukemia cell lines.
      Seventeen (57%) breakpoints were mapped at five breakpoint cluster sites, BCS-LL1
      to LL5, each of <15 bp. Two breakpoint cluster sites were located within the ARF
      and CDKN2B loci, respectively, whereas the remaining three were located >100 kb
      distal to the CDKN2A, ARF, and CDKN2B loci. The sequences of breakpoint junctions
      indicated that deletions in the 11 (73%) cell lines were mediated by illegitimate
      V(D)J recombination targeted at the five BCS-LL and six other sites, which
      contain sequences similar to recombination signal sequences for V(D)J
      recombination. An extrachromosomal V(D)J recombination assay indicated that BCS
      LL3, at which the largest number of breakpoints (i.e. five breakpoints) was
      clustered, has a V(D)J recombination potential 150-fold less than the consensus
      recombination signal sequence. Three other BCS-LLs tested also showed V(D)J
      recombination potential, although it was lower than that of BCS-LL3. These
      results indicated that illegitimate V(D)J recombination, which was targeted at
      several ectopic recombination signal sequences widely distributed in 9p21, caused
      a large fraction of 9p21 deletions in lymphoid leukemia.

PMID- 12228236
TI  - Apolipoprotein-mediated cellular lipid release requires replenishment of
      sphingomyelin in a phosphatidylcholine-specific phospholipase C-dependent manner.
AB  - When sphingomyelin is digested by sphingomyelinase in the plasma membrane of rat
      astrocytes, productions of sphingomyelin, diacylglycerol, and phosphatidylcholine
      are stimulated. D609, an inhibitor of phosphatidylcholine-specific phospholipase
      C, suppressed these effects. Similarly, when apolipoprotein A-I removed cellular
      cholesterol, phosphatidylcholine, and sphingomyelin to generate high density
      lipoprotein, cholesterol synthesis from acetate subsequently increased, and
      sphingomyelin synthesis from acetate and serine also increased. D609 inhibited
      these effects again. D609 also inhibited the cholesterol removal by apoA-I not
      only from the astrocytes but also from BALB/3T3 and RAW264 cells. D609 decreased
      cholesterol synthesis, although D609 did not directly inhibit
      hydroxymethylglutaryl-CoA reductase. ApoA-I-stimulated translocation of newly
      synthesized cholesterol to cytosol was also decreased by D609. A diacylglycerol
      analog increased the apoA-I-mediated cholesterol release, whereas ceramide did
      not influence it. We concluded that removal of cellular sphingomyelin by
      apolipoproteins is replenished by transfer of phosphorylcholine from
      phosphatidylcholine to ceramide, and this reaction may limit the removal of
      cholesterol by apoA-I. This reaction also produces diacylglycerol that
      potentially triggers subsequent cellular signal cascades and regulates
      intracellular cholesterol trafficking.

PMID- 12228237
TI  - Contribution of the mevalonate and methylerythritol phosphate pathways to the
      biosynthesis of gibberellins in Arabidopsis.
AB  - Gibberellins (GAs) are diterpene plant hormones essential for many developmental
      processes. Although the GA biosynthesis pathway has been well studied, our
      knowledge on its early stage is still limited. There are two possible routes for
      the biosynthesis of isoprenoids leading to GAs, the mevalonate (MVA) pathway in
      the cytosol and the methylerythritol phosphate (MEP) pathway in plastids. To
      distinguish these possibilities, metabolites from each isoprenoid pathway were
      selectively labeled with (13)C in Arabidopsis seedlings. Efficient (13)C-labeling
      was achieved by blocking the endogenous pathway chemically or genetically during
      the feed of a (13)C-labeled precursor specific to the MVA or MEP pathways. Gas
      chromatography-mass spectrometry analyses demonstrated that both MVA and MEP
      pathways can contribute to the biosyntheses of GAs and campesterol, a cytosolic
      sterol, in Arabidopsis seedlings. While GAs are predominantly synthesized through
      the MEP pathway, the MVA pathway plays a major role in the biosynthesis of
      campesterol. Consistent with some crossover between the two pathways, phenotypic
      defects caused by the block of the MVA and MEP pathways were partially rescued by
      exogenous application of the MEP and MVA precursors, respectively. We also
      provide evidence to suggest that the MVA pathway still contributes to GA
      biosynthesis when this pathway is limiting.

PMID- 12228238
TI  - Copper-regulated trafficking of the Menkes disease copper ATPase is associated
      with formation of a phosphorylated catalytic intermediate.
AB  - The Menkes protein (MNK; ATP7A) is a copper-transporting P-type ATPase that is
      defective in the copper deficiency disorder, Menkes disease. MNK is localized in
      the trans-Golgi network and transports copper to enzymes synthesized within
      secretory compartments. However, in cells exposed to excessive copper, MNK
      traffics to the plasma membrane where it functions in copper efflux. A conserved
      feature of all P-type ATPases is the formation of an acyl-phosphate intermediate,
      which occurs as part of the catalytic cycle during cation transport. In this
      study we investigated the effect of mutations within conserved catalytic regions
      of MNK on intracellular localization and trafficking from the trans-Golgi network
      (TGN). Our findings suggest that mutations that block formation of the
      phosphorylated catalytic intermediate also prevent copper-induced relocalization
      of MNK from the TGN. Furthermore, mutations in the phosphatase domain, which
      resulted in hyperphosphorylation of MNK, caused constitutive trafficking from the
      TGN to the plasma membrane. A similar effect on trafficking was observed with a
      phosphatase mutation in the closely related copper ATPase, ATP7B, affected in
      Wilson disease. These findings suggest that the copper-induced trafficking of the
      Menkes and Wilson disease copper ATPases is associated with the phosphorylated
      intermediate that is formed during the catalysis of these pumps. Our findings
      describe a novel mechanism for regulating the subcellular location of a transport
      protein involving the recognition of intermediate conformations during catalysis.

PMID- 12228239
TI  - Specific recruitment of human cohesin to laser-induced DNA damage.
AB  - Cohesin is a conserved multiprotein complex that plays an essential role in
      sister chromatid cohesion. During interphase, cohesin is required for the
      establishment of cohesion following DNA replication. Because cohesin mutants
      resulted in increased sensitivity to DNA damage, a role for cohesin in DNA repair
      was also suggested. However, it was unclear whether this was due to general
      perturbation of cohesion or whether cohesin has a specialized role at the damage
      site. We therefore used a laser microbeam to create DNA damage at discrete sites
      in the cell nucleus and observed specific in vivo assembly of proteins at these
      sites by immunofluorescent detection. We observed that human cohesin is recruited
      to the damage site immediately after damage induction. Analysis of mutant cells
      revealed that cohesin recruitment to the damage site is dependent on the DNA
      double-strand break repair factor Mre11/Rad50 but not ATM or Nbs1. Consistently,
      Mre11/Rad50 and cohesin interact with each other in an interphase-specific
      manner. This interaction peaks in S/G(2) phase, during which cohesin is recruited
      to the DNA damage. Our results demonstrate the S/G(2)-specific and Mre11/Rad50
      dependent recruitment of human cohesin to DNA damage, suggesting a specialized
      subfunction for cohesin in cell cycle-specific DNA double strand break repair.

PMID- 12228240
TI  - A higher plant mitochondrial homologue of the yeast m-AAA protease. Molecular
      cloning, localization, and putative function.
AB  - Mitochondrial AAA metalloproteases play a fundamental role in mitochondrial
      biogenesis and function. They have been identified in yeast and animals but not
      yet in plants. This work describes the isolation and sequence analysis of the
      full-length cDNA from the pea (Pisum sativum) with significant homology to the
      yeast matrix AAA (m-AAA) protease. The product of this clone was imported into
      isolated pea mitochondria where it was processed to its mature form (PsFtsH). We
      have shown that the central region of PsFtsH containing the chaperone domain is
      exposed to the matrix space. Furthermore, we have demonstrated that the pea
      protease can complement respiration deficiency in the yta10 and/or yta12 null
      yeast mutants, indicating that the plant protein can compensate for the loss of
      at least some of the important m-AAA functions in yeast. Based on biochemical
      experiments using isolated pea mitochondria, we propose that PsFtsH-like m-AAA is
      involved in the accumulation of the subunit 9 of the ATP synthase in the
      mitochondrial membrane.

PMID- 12228241
TI  - Function and solution structure of huwentoxin-IV, a potent neuronal tetrodotoxin
      (TTX)-sensitive sodium channel antagonist from Chinese bird spider Selenocosmia
      huwena.
AB  - We have isolated a highly potent neurotoxin from the venom of the Chinese bird
      spider, Selenocosmia huwena. This 4.1-kDa toxin, which has been named huwentoxin
      IV, contains 35 residues with three disulfide bridges: Cys-2-Cys-17, Cys-9-Cys
      24, and Cys-16-Cys-31, assigned by a chemical strategy including partial
      reduction of the toxin and sequence analysis of the modified intermediates. It
      specifically inhibits the neuronal tetrodotoxin-sensitive (TTX-S) voltage-gated
      sodium channel with the IC(50) value of 30 nm in adult rat dorsal root ganglion
      neurons, while having no significant effect on the tetrodotoxin-resistant (TTX-R)
      voltage-gated sodium channel. This toxin seems to be a site I toxin affecting the
      sodium channel through a mechanism quite similar to that of TTX: it suppresses
      the peak sodium current without altering the activation or inactivation kinetics.
      The three-dimensional structure of huwentoxin-IV has been determined by two
      dimensional (1)H NMR combined with distant geometry and simulated annealing
      calculation by using 527 nuclear Overhauser effect constraints and 14 dihedral
      constraints. The resulting structure is composed of a double-stranded
      antiparallel beta-sheet (Leu-22-Ser-25 and Trp-30-Tyr-33) and four turns (Glu-4
      Lys-7, Pro-11-Asp-14, Lys-18-Lys-21 and Arg-26-Arg-29) and belongs to the
      inhibitor cystine knot structural family. After comparison with other toxins
      purified from the same species, we are convinced that the positively charged
      residues of loop IV (residues 25-29), especially residue Arg-26, must be crucial
      to its binding to the neuronal tetrodotoxin-sensitive voltage-gated sodium
      channel.

PMID- 12228242
TI  - Functional analysis of Toxoplasma gondii protease inhibitor 1.
AB  - We have characterized a Kazal family serine protease inhibitor, Toxoplasma gondii
      protease inhibitor 1 (TgPI-1), in the obligate intracellular parasite Toxoplasma
      gondii. TgPI-1 contains four inhibitor domains predicted to inhibit trypsin,
      chymotrypsin, and elastase. Antibodies against recombinant TgPI-1 detect two
      polypeptides, of 43 and 41 kDa, designated TgPI-1(43) and TgPI-1(41), in
      tachyzoites, bradyzoites, and sporozoites. TgPI-1(43) and TgPI-1(41) are secreted
      constitutively from dense granules into the excreted/secreted antigen fraction as
      well as the parasitophorous vacuole that T. gondii occupies during intracellular
      replication. Recombinant TgPI-1 inhibits trypsin, chymotrypsin, pancreatic
      elastase, and neutrophil elastase. Immunoprecipitation studies with anti-rTgPI-1
      antibodies reveal that recombinant TgPI-1 forms a complex with trypsin that is
      dependent on interactions with the active site of the protease. TgPI-1 is the
      first anti-trypsin/chymotrypsin inhibitor to be identified in bradyzoites and
      sporozoites, stages of the parasite that would be exposed to proteolytic enzymes
      in the digestive tract of the host.

PMID- 12228243
TI  - Molecular characterization of a metastatic neuroendocrine cell cancer arising in
      the prostates of transgenic mice.
AB  - The features and functions of prostatic neuroendocrine (NE) cells remain ill
      defined. Neuroendocrine differentiation (NED) in adenocarcinoma of the human
      prostate (CaP) is associated with more aggressive disease, but the underlying
      mediators are poorly understood. We examined these issues in transgenic mice that
      utilize regulatory elements from the cryptdin-2 gene (Defcr2) to express simian
      virus 40 large T antigen (TAg) in prostatic NE cells. CR2-TAg mice develop
      prostatic intraepithelial neoplasia at 8 weeks of age, 1 week after the onset of
      TAg expression. An invasive phase follows 2-4 weeks later, with lymph node,
      liver, lung, brain, and bone metastases appearing within 16 weeks. DNA microarray
      studies revealed 122 mRNAs that were increased >/=2-fold in duplicate assays of
      16-week-old CR2-TAg versus normal prostates. Thirty two transcripts encode
      proteins associated with neurons and endocrine cells (e.g. basic helix loop
      helix, SRY-related high mobility group box and sine-oculis homeobox transcription
      factors, Hu RNA-binding proteins, neuronatin, Racgap1, collapsin response
      mediator protein-1, synaptotagmin-1, proprotein convertase, and secretogranins).
      Follow-up studies of candidate mediators and biomarkers of differentiation/growth
      in the microarray data set involved real time quantitative reverse transcriptase
      PCR assays of laser capture microdissected NE cells from CR2-TAg prostates plus
      liver metastases, and immunohistochemical comparisons of transgenic mouse
      prostates and 35 human CaP samples. Our findings include (a) expression of the
      bHLH mouse achaete-scute homolog (mASH1) in normal and CR2-TAg NE cells and foci
      of NED in human CaP, (b) glutamic acid decarboxylase and its product (gamma
      aminobutyric acid) in neoplastic NE cells juxtaposed next to cohorts of normal
      gamma-aminobutyric acid receptor expressing secretory cells (a potential route
      for paracrine interactions between these two epithelial lineages), and (c)
      aromatic l-amino-acid decarboxylase, but not its dopamine/serotonin products, in
      CR2-TAg NE cells and NED. These results underscore the value of CR2-TAg mice for
      characterizing normal NE cell biology and tumorigenesis.

PMID- 12228244
TI  - Polymorphisms in the human high sulfur hair keratin-associated protein 1, KAP1,
      gene family.
AB  - Hair fiber differentiation and maturation involves the close interaction between
      hair keratins and their associated proteins, KAPs. Recently, a cluster of seven
      human KAP multigen families has been identified on chromosome 17q12-21 among
      which were four hKAP1 genes (hKAP1.1B, hKAP1.3, hKAP1.4, and hKAP1.5). In
      addition, there were previous as well as recent reports on four additional hKAP1
      genes (hKAP1.1A, hKAP1.2, hKAP1.6, and hKAP1.7) with unknown chromosomal
      location. In this study, we have analyzed these eight hKAP1 genes in unrelated
      Japanese and Caucasian individuals and discovered that hKAP1.1A, hKAP1.6, and
      hKAP1.7 represent size polymorphisms of the hKAP1.1B gene. In addition, we show
      that hKAP1.2 as well as three hitherto unknown genes (hKAP1.8A, hKAP1.8B, and
      hKAP1.9) are size polymorphisms of the hKAP1.3 gene. In contrast, no polymorphic
      alleles were found for the hKAP1.4 and hKAP1.5 genes. We provide evidence that
      the polymorphic hKAP1.1B and hKAP1.3 alleles arose mainly by intragenic deletion
      and/or duplication events of distinct pentapeptide repeats typical for hKAP1
      genes. We also demonstrate the occurrence of both frequent and rare population
      specific hKAP1.1B and hKAP1.3 alleles, which were obviously generated after the
      divergence of the Caucasian and Japanese lineage. In addition, by means of a pan
      hKAP1 antibody, we confirm the previous hKAP1 family mRNA localization data in
      the middle to upper cortex of the human anagen hair follicle.

PMID- 12228245
TI  - A subset of Plasmodium falciparum SERA genes are expressed and appear to play an
      important role in the erythrocytic cycle.
AB  - The Plasmodium falciparum serine repeat antigen (SERA) has shown considerable
      promise as a blood stage vaccine for the control of malaria. A related protein,
      SERPH, has also been described in P. falciparum. Whereas their biological role
      remains unknown, both proteins possess papain-like protease domains that may
      provide attractive targets for therapeutic intervention. Genomic sequencing has
      recently shown that SERA and SERPH are the fifth and sixth genes, respectively,
      in a cluster of eight SERA homologues present on chromosome 2. In this paper, the
      expression and functional relevance of these eight genes and of a ninth SERA
      homologue found on chromosome 9 were examined in blood stage parasites. Using
      reverse transcriptase-PCR and microarray approaches, we demonstrate that whereas
      mRNA to all nine SERA genes is synthesized late in the erythrocytic cycle, it is
      those genes in the central region of the chromosome 2 cluster that are
      substantially up-regulated at this time. Using antibodies specific to each SERA,
      it was apparent that SERA4 to -6, and possibly also SERA9, are synthesized in
      blood stage parasites. The reactivity of antibodies from malaria-immune
      individuals with the SERA recombinant proteins suggested that SERA2 and SERA3 are
      also expressed at least in some parasite populations. To examine whether SERA
      genes are essential to blood stage growth, each of the eight chromosome 2 SERA
      genes was targeted for disruption. Whereas genes at the periphery of the cluster
      were mostly dispensable (SERA2 and -3 and SERA7 and -8), those in the central
      region (SERA4 to -6) could not be disrupted. The inability to disrupt SERA4, -5,
      and -6 is consistent with their apparent dominant expression and implies an
      important role for these genes in maintenance of the erythrocytic cycle.

PMID- 12228246
TI  - Agonist recognition sites in the cytosolic tails of vanilloid receptor 1.
AB  - Vanilloid receptor 1 (VR1), a ligand-gated ion channel activated by vanilloids,
      acid, and heat, is a molecular detector that integrates multiple modes of pain.
      Although the function and the biophysical properties of the channel are now
      known, the regions of VR1 that recognize ligands are largely unknown. By the
      stepwise deletion of VR1 and by chimera construction using its capsaicin
      insensitive homologue, VRL1, we localized key amino acids, Arg-114 and Glu-761,
      in the N- and C-cytosolic tails, respectively, that determine ligand binding.
      Point mutations of the two key residues resulted in a loss of sensitivity to
      capsaicin and a concomitant loss of specific binding to [(3)H]resiniferatoxin, a
      potent vanilloid. Furthermore, changes in the charges of the two amino acids
      blocked capsaicin-sensitive currents and ligand binding without affecting current
      responses to heat. Thus, these two regions in the cytoplasmic tails of VR1
      provide structural elements for its hydrophilic interaction with vanilloids and
      might constitute a long-suspected binding pocket.

PMID- 12228247
TI  - Endoglin expression is regulated by transcriptional cooperation between the
      hypoxia and transforming growth factor-beta pathways.
AB  - Endoglin is a transforming growth factor-beta (TGF-beta) co-receptor expressed
      mainly on endothelial cells and involved in cardiovascular development,
      angiogenesis, and vascular remodeling. This is illustrated by the fact that
      mutations in the endoglin gene give rise to hereditary hemorrhagic telangiectasia
      type 1, a dominant vascular disease with clinical manifestations that originate
      by a mechanism of haploinsufficiency. Thus, studies on the regulated expression
      of endoglin are crucial to devising therapeutic strategies for hereditary
      hemorrhagic telangiectasia type 1. Endoglin is highly expressed in the
      neovasculature associated with hypoxia such as ischemic tissues and tumors, but
      the molecular mechanism of this up-regulation is unknown. Here, we have
      investigated the possible regulation of endoglin expression by hypoxia. Surface
      protein, transcript, and promoter activity levels of endoglin were found to be up
      regulated by hypoxia, indicating that the regulation takes place at the
      transcriptional level. A hypoxia-responsive element downstream of the main
      transcription start site of the endoglin gene was functionally characterized.
      Whereas hypoxia alone moderately stimulated endoglin transcription, addition of
      TGF-beta under hypoxic conditions resulted in transcriptional cooperation between
      both signaling pathways, leading to marked stimulation of endoglin expression.
      Because basal endoglin transcription is sustained by Sp1, and TGF-beta and
      hypoxia signaling pathways are mediated by Smad proteins and hypoxia-inducible
      factor-1 (HIF-1), respectively, the involvement of these transcription factors
      was analyzed. Functional and co-immunoprecipitation experiments demonstrated the
      existence of a multiprotein complex (Sp1.Smad3.HIF-1) on the endoglin promoter,
      mediating the cooperation between the hypoxia and TGF-beta pathways. Within this
      multiprotein complex, Smad3 appears to function not only as a coactivator factor,
      but also as an adaptor between HIF-1 and Sp1. We propose that basal endoglin
      transcription (highly dependent on Sp1) may switch from a constitutive to an
      inducible state through Sp1 interaction with HIF-1 and Smad transcription
      factors, induced by hypoxia and TGF-beta, respectively.

PMID- 12228248
TI  - Genotoxin-induced Rad9-Hus1-Rad1 (9-1-1) chromatin association is an early
      checkpoint signaling event.
AB  - Rad17, Rad1, Hus1, and Rad9 are key participants in checkpoint signaling pathways
      that block cell cycle progression in response to genotoxins. Biochemical and
      molecular modeling data predict that Rad9, Hus1, and Rad1 form a heterotrimeric
      complex, dubbed 9-1-1, which is loaded onto chromatin by a complex of Rad17 and
      the four small replication factor C (RFC) subunits (Rad17-RFC) in response to DNA
      damage. It is unclear what checkpoint proteins or checkpoint signaling events
      regulate the association of the 9-1-1 complex with DNA. Here we show that
      genotoxin-induced chromatin binding of 9-1-1 does not require the Rad9-inducible
      phosphorylation site (Ser-272). Although we found that Rad9 undergoes an
      additional phosphatidylinositol 3-kinase-related kinase (PIKK)-dependent
      posttranslational modification, we also show that genotoxin-triggered 9-1-1
      chromatin binding does not depend on the catalytic activity of the PIKKs ataxia
      telangiectasia-mutated (ATM), ataxia telangiectasia and Rad3-related (ATR), or
      DNA-PK. Additionally, 9-1-1 chromatin binding does not require DNA replication,
      suggesting that the complex can be loaded onto DNA in response to DNA structures
      other than stalled DNA replication forks. Collectively, these studies demonstrate
      that 9-1-1 chromatin binding is a proximal event in the checkpoint signaling
      cascade.

PMID- 12228249
TI  - Substrate-dependent competency of the catalytic triad of prolyl oligopeptidase.
AB  - Prolyl oligopeptidase, a serine peptidase unrelated to trypsin and subtilisin, is
      implicated in memory disorders and is an important target of drug design. The
      catalytic competence of the Asp(641) residue of the catalytic triad (Ser(554),
      Asp(641), His(680)) was studied using the D641N and D641A variants of the enzyme.
      Both variants displayed 3 orders of magnitude reduction in k(cat)/K(m) for
      benzyloxycarbonyl-Gly-Pro-2-naphthylamide. Using an octapeptide substrate, the
      decrease was 6 orders of magnitude, whereas with Z-Gly-Pro-4-nitrophenyl ester
      there was virtually no change in k(cat)/K(m). This indicates that the
      contribution of Asp(641) is very much dependent on the substrate-leaving group,
      which was not the case for the classic serine peptidase, trypsin. The rate
      constant for benzyloxycarbonyl-Gly-Pro-thiobenzylester conformed to this series
      as demonstrated by a method designed for monitoring the hydrolysis of thiolesters
      in the presence of thiol groups. Alkylation of His(680) with Z-Gly-Pro-CH(2)Cl
      was concluded with similar rate constants for wild-type and D641A variant.
      However, kinetic measurements with Z-Gly-Pro-OH, a product-like inhibitor,
      indicated that the His(680) is not accessible in the enzyme variants. Crystal
      structure determination of these mutants revealed subtle perturbations related to
      the catalytic activity. Many of these observations show differences in the
      catalysis between trypsin and prolyl oligopeptidase.

PMID- 12228250
TI  - A novel epimerization system in fungal secondary metabolism involved in the
      conversion of isopenicillin N into penicillin N in Acremonium chrysogenum.
AB  - The epimerization step that converts isopenicillin N into penicillin N during
      cephalosporin biosynthesis has remained uncharacterized despite its industrial
      relevance. A transcriptional analysis of a 9-kb region located downstream of the
      pcbC gene revealed the presence of two transcripts that correspond to the genes
      named cefD1 and cefD2 encoding proteins with high similarity to long chain acyl
      CoA synthetases and acyl-CoA racemases from Mus musculus, Homo sapiens, and
      Rattus norvegicus. Both genes are expressed in opposite orientations from a
      bidirectional promoter region. Targeted inactivation of cefD1 and cefD2 was
      achieved by the two-marker gene replacement procedure. Disrupted strains lacked
      isopenicillin N epimerase activity, were blocked in cephalosporin C production,
      and accumulated isopenicillin N. Complementation in trans of the disrupted
      nonproducer mutant with both genes restored epimerase activity and cephalosporin
      biosynthesis. However, when cefD1 or cefD2 were introduced separately into the
      double-disrupted mutant, no epimerase activity was detected, indicating that the
      concerted action of both proteins encoded by cefD1 and cefD2 is required for
      epimerization of isopenicillin N into penicillin N. This epimerization system
      occurs in eukaryotic cells and is entirely different from the known epimerization
      systems involved in the biosynthesis of bacterial beta-lactam antibiotics.

PMID- 12228251
TI  - The Shq1p.Naf1p complex is required for box H/ACA small nucleolar
      ribonucleoprotein particle biogenesis.
AB  - Small nucleolar ribonucleoprotein particles (snoRNPs) are essential cofactors in
      ribosomal RNA metabolism. Although snoRNP composition has been thoroughly
      characterized, the biogenesis process of these particles is poorly understood. We
      have identified two proteins from the yeast Saccharomyces cerevisiae,
      Yil104c/Shq1p and Ynl124w/Naf1p, which are essential and required for the
      stability of box H/ACA snoRNPs. Depletion of either Shq1p or Naf1p leads to a
      dramatic and specific decrease in box H/ACA snoRNA levels in vivo. A severe
      concomitant defect in ribosomal RNA processing is observed, consistent with the
      depletion of this family of snoRNAs. Shq1p and Naf1p show nuclear localization
      and interact with Nhp2p and Cbf5p, two core proteins of mature box H/ACA snoRNPs.
      Shq1p and Naf1p form a complex, but they are not strongly associated with box
      H/ACA snoRNPs. We propose that Shq1p and Naf1p are involved in the early
      biogenesis steps of box H/ACA snoRNP assembly.

PMID- 12228252
TI  - Acyl-enzyme complexes between tissue-type plasminogen activator and neuroserpin
      are short-lived in vitro.
AB  - The serine protease tissue-type plasminogen activator (t-PA) initiates the
      fibrinolytic protease cascade and plays a significant role in motor learning,
      memory, and neuronal cell death induced by excitotoxin and ischemia. In the
      fibrinolytic system, the serpin PAI-1 negatively regulates the enzymatic activity
      of both single-chain and two-chain t-PA (sct-PA and tct-PA). In the central
      nervous system, neuroserpin (NSP) is a serpin thought to regulate t-PA enzymatic
      activity. We report that although both sct-PA and tct-PA rapidly form acyl-enzyme
      complexes with NSP in vitro, the interactions are short-lived, rapidly
      progressing to complete cleavage of NSP and regeneration of fully active enzyme.
      All NSP molecules appear to transit through the detectable acyl-enzyme
      intermediate and progress to completion of cleavage; no subpopulation that
      functions as a pure substrate was detected. Likewise, all molecules were
      reactive, with no evidence of a latent subpopulation. The interactions between
      NSP and t-PA were distinct from those between plasmin and NSP, wherein the same
      peptide bond was cleaved but there was no evidence of a detectable plasmin-NSP
      acyl-enzyme complex. The interactions between t-PA and NSP contrast with the
      formation of long-lived, physiologically irreversible acyl-enzyme complexes
      between t-PA and PAI-1, suggesting that the physiologic effect of t-PA-NSP
      interactions may be more complex than previously thought.

PMID- 12228253
TI  - Crystal structure of human sex hormone-binding globulin in complex with 2
      methoxyestradiol reveals the molecular basis for high affinity interactions with
      C-2 derivatives of estradiol.
AB  - In a crystal structure of the amino-terminal laminin G-like domain of human sex
      hormone-binding globulin (SHBG), the biologically active estrogen metabolite, 2
      methoxyestradiol (2-MeOE2), binds in the same orientation as estradiol. The high
      affinity of SHBG for 2-MeOE2 relies primarily on hydrogen bonding between the
      hydroxyl at C-3 of 2-MeOE2 and Asp(65) and an interaction between the methoxy
      group at C-2 and the amido group of Asn(82). Accommodation of the 2-MeOE2 methoxy
      group causes an outward displacement of residues Ser(128)-Pro(130), which appears
      to disorder and displace the loop region (Leu(131)-His(136)) that covers the
      steroid-binding site. This could influence the binding kinetics of 2-MeOE2 and/or
      facilitate ligand-dependent interactions between SHBG and other proteins.
      Occupancy of a zinc-binding site reduces the affinity of SHBG for 2-MeOE2 and
      estradiol in the same way. The higher affinity of SHBG for estradiol derivatives
      with a halogen atom at C-2 is due to either enhanced hydrogen bonding between the
      hydroxyl at C-3 and Asp(65) (2-fluoroestradiol) or accommodation of the
      functional group at C-2 (2-bromoestradiol), rather than an interaction with
      Asn(82). By contrast, the low affinity of SHBG for 2-hydroxyestradiol can be
      attributed to intra-molecular hydrogen bonding between the hydroxyls in the
      aromatic steroid ring A, which generates a steric clash with the amido group of
      Asn(82). Understanding how C-2 derivatives of estradiol interact with SHBG could
      facilitate the design of biologically active synthetic estrogens.

PMID- 12228254
TI  - Recognition of eukaryotic initiation factor 4G isoforms by picornaviral
      proteinases.
AB  - The leader proteinase (L(pro)) of foot and mouth disease virus is a papain-like
      cysteine proteinase. After processing itself from the polyprotein, L(pro) then
      cleaves the host protein eukaryotic initiation factor (eIf) 4GI, thus preventing
      protein synthesis from capped mRNA in the infected cell. We have investigated
      L(pro) interaction with eIF4GI and its isoform, eIF4GII. L(pro), expressed as a
      catalytically inactive fusion protein with glutathione S-transferase, binds
      specifically to eIF4G isomers in rabbit reticulocyte lysates. Deletion and
      specific mutagenesis were used to map the binding domain on L(pro) to residues
      183-195 of the C-terminal extension and to residue Cys(133). These residues of
      the C-terminal extension and Cys(133) are adjacent in the crystal structure but
      lie about 25 A from the active site. The region on eIF4GI recognized by the
      L(pro) C-terminal extension was mapped to residues 640-669 using eIF4GI fragments
      generated by proteolysis or by in vitro translation. The L(pro) cleavage site at
      Gly(674) downward arrow Arg(675) was not necessary for binding. Similar
      experiments with human rhinovirus 2A proteinase (2A(pro)), a chymotrypsin-like
      cysteine proteinase that also cleaves eIF4G isoforms, revealed that 2A(pro) can
      also bind to eIF4GI fragments lacking its cleavage site. These experiments
      strongly suggest a novel interaction between picornaviral proteinases and eIF4G
      isoforms.

PMID- 12228255
TI  - X-ray structure of two crystalline forms of a streptomycete ribonuclease with
      cytotoxic activity.
AB  - Ribonuclease (RNase) Sa3 is secreted by the Gram-positive bacterium Streptomyces
      aureofaciens. The enzyme catalyzes the cleavage of RNA on the 3' side of
      guanosine residues. Here, x-ray diffraction analysis was used to determine the
      three-dimensional structure of two distinct crystalline forms of RNase Sa3 to a
      resolution of 2.0 and 1.7 A. These two structures are similar to each other as
      well as to that of a homolog, RNase Sa. All of the key active-site residues of
      RNase Sa (Asn(42), Glu(44), Glu(57), Arg(72), and His(88)) are located in the
      putative active site of RNase Sa3. Also herein, RNase Sa3 is shown to be toxic to
      human erythroleukemia cells in culture. Like onconase, which is an amphibian
      ribonuclease in Phase III clinical trials as a cancer chemotherapeutic, RNase Sa3
      is not inhibited by the cytosolic ribonuclease inhibitor protein. Thus, a
      prokaryotic ribonuclease can be toxic to mammalian cells.

PMID- 12228256
TI  - Apple 1-aminocyclopropane-1-carboxylate synthase in complex with the inhibitor L
      aminoethoxyvinylglycine. Evidence for a ketimine intermediate.
AB  - The 1.6-A crystal structure of the covalent ketimine complex of apple 1
      aminocyclopropane-1-carboxylate (ACC) synthase with the potent inhibitor l
      aminoethoxyvinylglycine (AVG) is described. ACC synthase catalyzes the committed
      step in the biosynthesis of ethylene, a plant hormone that is responsible for the
      initiation of fruit ripening and for regulating many other developmental
      processes. AVG is widely used in plant physiology studies to inhibit the activity
      of ACC synthase. The structural assignment is supported by the fact that the
      complex absorbs maximally at 341 nm. These results are not in accord with the
      recently reported crystal structure of the tomato ACC synthase AVG complex, which
      claims that the inhibitor only associates noncovalently. The rate constant for
      the association of AVG with apple ACC synthase was determined by stopped-flow
      spectrophotometry (2.1 x 10(5) m(-1) s(-1)) and by the rate of loss of enzyme
      activity (1.1 x 10(5) m(-1) s(-1)). The dissociation rate constant determined by
      activity recovery is 2.4 x 10(-6) s(-1). Thus, the calculated K(d) value is 10-20
      pm.

PMID- 12228257
TI  - Functional blocking of Staphylococcus aureus adhesins following growth in ex vivo
      media.
AB  - Defining the role of Staphylococcus aureus adhesins in disease pathogenesis may
      depend on the use of bacteria grown in culture media that more closely reflect
      the human milieu than conventional broth. This study examined the functional
      effect on S. aureus adhesins following growth in an ex vivo medium containing a
      complex mixture of human proteins (used peritoneal dialysate) relative to growth
      in Todd-Hewitt broth. The adherence of S. aureus, cultured in dialysate, to
      fibronectin and fibrinogen was markedly reduced despite the expresion of full
      length ClfA, ClfB, and fibronectin-binding proteins. Growth in dialysate resulted
      in the acquisition of a surface coat, as visualized by transmission electron
      microscopy, which was shown to contain fibronectin, fibrinogen, and
      immunoglobulins. Adherence of S. aureus to fibrinogen following growth in
      dialysate was significantly reduced by expression of protein A but was restored
      following growth in immunoglobulin-depleted dialysate. We conclude that bacterial
      adherence to solid-phase protein is critically dependent on the culture medium,
      that S. aureus adhesins may become saturated with target protein prior to contact
      with solid surfaces, and that there is an interaction between fibrinogen-binding
      proteins and immunoglobulin bound to protein A following contact with host
      proteins. These findings have important implications for future studies of S.
      aureus adhesins.

PMID- 12228258
TI  - The class A macrophage scavenger receptor is a major pattern recognition receptor
      for Neisseria meningitidis which is independent of lipopolysaccharide and not
      required for secretory responses.
AB  - Macrophages (Mphi) play a key role in the pathogenesis of invasive meningococcal
      infections. The roles of two pattern recognition molecules, the Mphi scavenger
      receptor (SR-A) and Toll-like receptor 4 (TLR-4), have been investigated using
      bone marrow culture-derived Mphi (BMMphi). Surprisingly, a comparison of BMMphi
      from wild-type and SR-A knockout (SR-A(-/-)) mice showed that nonopsonic
      phagocytosis of meningococci was mediated almost exclusively via SR-A. Previous
      studies have demonstrated only a partial involvement of the receptor in the
      uptake of other bacteria, such as Escherichia coli. Interestingly, we also show
      that lipopolysaccharide (LPS) was not the ligand for the receptor on these
      organisms. Further study of the downstream events of SR-A-mediated ingestion of
      Neisseria meningitidis demonstrated that SR-A was not required for cytokine
      production. To determine the bacterial and host factors required to stimulate
      Mphi activation, we examined TLR-4-deficient Mphi from C3H/HeJ mice and LPS
      deficient meningococci. TLR-4-deficient cells elaborated reduced amounts of tumor
      necrosis factor alpha, interleukin-12 (IL-12), and IL-10, even though ingestion
      via SR-A was unaffected in these cells. Similarly, although there was no change
      in SR-A-mediated ingestion of LPS-deficient meningococci, the mutant failed to
      stimulate a Mphi-dependent cytokine response. Thus, we show that Mphi SR-A
      mediates opsonin-independent uptake of N. meningitidis independently of lipid A
      and that this activity is uncoupled from the Mphi secretion of proinflammatory
      cytokines, which provides a basis for further investigation of the role of this
      receptor in meningococcal disease in humans.

PMID- 12228259
TI  - The alternative sigma factor sigma(E) plays an important role in intestinal
      survival and virulence in Vibrio cholerae.
AB  - The alternative sigma factor sigma(E) (RpoE) is involved in the response to
      extracytoplasmic stress and plays a role in the virulence of a variety of
      different bacteria. To assess the role of sigma(E) in Vibrio cholerae
      pathogenesis, a DeltarpoE mutant was constructed and analyzed using the infant
      mouse model. The results here show that sigma(E) contributes significantly to the
      virulence of V. cholerae. The DeltarpoE mutant was highly attenuated with a 50%
      lethal dose more than 3 logs higher than that for the parental strain, and its
      ability to colonize the intestine was reduced approximately 30-fold. A time
      course of infection revealed that the number of CFU of the DeltarpoE mutant was
      approximately 1 log lower than that of the parental strain by 12 h
      postinoculation and decreased further by 24 h. The defect in virulence in the
      DeltarpoE mutant thus appears to be a diminished ability to survive within the
      intestinal environment. The results here also show that sigma(E) is not required
      for growth and survival of V. cholerae in vitro at high temperatures but is
      required under other stressful conditions, such as in the presence of 3% ethanol.
      As in Escherichia coli, the expression of rpoE in V. cholerae is dependent upon
      two promoters located upstream of the gene, P1 and P2. P1 appears to be sigma(70)
      dependent, whereas the downstream promoter, P2, is positively autoregulated by
      sigma(E).

PMID- 12228260
TI  - Immune responses to novel pneumococcal proteins pneumolysin, PspA, PsaA, and CbpA
      in adenoidal B cells from children.
AB  - Studies of mice suggest that pneumococcal proteins, including PspA, pneumolysin,
      PsaA, and CbpA, are promising vaccine candidates. To determine whether these
      proteins are good mucosal immunogens in humans, adenoidal lymphocytes from 20
      children who had adenoidectomies were isolated and tested by ELISpot for antigen
      specific antibody-secreting cells (ASCs). Cells were also cultured for 7 days in
      the presence of a concentrated culture supernatant (CCS) from a type 14 strain of
      pneumococcus which contained secreted pneumococcal proteins, including PspA,
      pneumolysin, PsaA, and CbpA, and then tested by ELISpot. ELISpot assays done on
      freshly isolated cells detected ASCs to all four antigens in most children
      studied. However, there were differences both between antigens and between
      isotypes. The densities of immunoglobulin G (IgG) ASCs against both PsaA and CbpA
      were significantly higher than those of ASCs for PspA and PdB (pneumolysin toxoid
      B) (P < 0.001). For all antigens, the numbers of IgA ASCs tended to be lower than
      those of both IgG and IgM ASCs. The numbers of anti-CbpA and -PsaA IgA ASCs were
      higher than those of anti-PdB IgA ASCs (P < 0.01). Concentrations of IgA
      antibodies to PspA and PsaA in saliva correlated with the numbers of IgA ASCs to
      PspA and PsaA in freshly isolated adenoidal cells, but no such correlation was
      found between salivary IgG antibody concentrations and IgG ASCs to the four
      antigens in adenoidal cells. In cultured cells, anti-PspA, -PsaA, and -CbpA IgG
      ASCs proliferated significantly, but only two of eight samples showed >2-fold
      increases in anti-CbpA and -PspA IgA ASCs after CCS stimulation. The results
      suggest that CbpA, PsaA, and PspA may be good upper respiratory mucosal antigens
      in children. Adenoids may be important inductive sites for memory IgG responses
      and important sources of salivary IgA. Some protein antigens may also prime for
      mucosal IgA memory. These data support the effort to explore mucosal immunization
      against pneumococcal infection.

PMID- 12228261
TI  - Essential role for verotoxin in sustained stress-activated protein kinase and
      nuclear factor kappa B signaling, stimulated by Escherichia coli O157:H7 in Vero
      cells.
AB  - The effects of Escherichia coli O157:H7 (strains E30480 and PM601) and the
      associated verotoxins (VTs), VT1 and VT2, on stress-activated protein kinase and
      nuclear factor kappa B (NF-kappaB) signaling were investigated with Vero cells,
      which are extremely sensitive to the cytotoxic effects of E. coli O157:H7 in
      vitro. Cell-free supernatants prepared from E30480 and PM601 cultures and
      purified VT1 and VT2 stimulated a strong and prolonged (>4-h) activation of both
      c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase. However,
      JNK activity stimulated in response to E30480 supernatants was substantially
      reduced following pretreatment with anti-VT1 and anti-VT2 antibodies, while a VT1
      and VT2 gene knockout mutant of PM601 was unable to stimulate JNK activity.
      E30480 supernatants also caused a sustained activation of NF-kappaB DNA binding,
      degradation of inhibitory kappa B alpha (IkappaBalpha), and an increase in
      inhibitory kappa B kinase alpha activity, although PM601 supernatants and VT1 and
      VT2 had no effect. However, preincubation with VTs prolonged the transient
      activation of NF-kappaB and IkappaBalpha degradation stimulated by either tumor
      necrosis factor alpha or interleukin 1beta, while preincubation with anti-VT
      antibodies prevented the prolonged loss of IkappaBalpha and partially reduced DNA
      binding in response to E30480 supernatants. These results strongly suggest that
      in Vero cells, VT plays an essential role in sustained JNK and NF-kappaB
      signaling in response to E. coli O157:H7 and that this action may underpin their
      cell-selective cytotoxic effects. These studies also suggest that another
      component released by strain E30480 contributes to the early activation of JNK
      and NF-kappaB.

PMID- 12228262
TI  - Contribution of membrane-damaging toxins to Bacillus endophthalmitis
      pathogenesis.
AB  - Membrane-damaging toxins are thought to be responsible for the explosive clinical
      course of Bacillus endophthalmitis. This study analyzed the contribution of
      phosphatidylinositol-specific phospholipase C (PI-PLC) and phosphatidylcholine
      specific phospholipase C (PC-PLC) to the pathogenesis of experimental Bacillus
      endophthalmitis. Isogenic mutants were constructed by insertion of lacZ into
      Bacillus thuringiensis genes encoding PI-PLC (plcA) and PC-PLC (plcB). Rabbit
      eyes were injected intravitreally with 2 log(10) CFU of strain BT407 (wild type),
      the PI-PLC mutant (BTplcA::lacZ), or the PC-PLC mutant (BTplcB::lacZ). The rates
      of decrease in retinal responses of eyes infected with the isogenic mutants were
      similar to that of wild type, with all infections resulting in elimination of
      retinal function by 18 h. Strain BT407 caused a significant increase in the
      latency of retinal responses at 6 h, but strains BTplcA::lacZ and BTplcB::lacZ
      did not. All strains elicited significant inflammatory cell influx into the
      anterior chamber by 12 h. Histologically, eyes infected with each strain were
      indistinguishable throughout the infection course. In this model, neither PI-PLC
      nor PC-PLC had an effect on the course or severity of experimental Bacillus
      endophthalmitis. Alterations in retinal responses early in infection may mark the
      beginnings of specific photoreceptor or glial cell dysfunction.

PMID- 12228263
TI  - BhuR, a virulence-associated outer membrane protein of Bordetella avium, is
      required for the acquisition of iron from heme and hemoproteins.
AB  - Iron (Fe) is an essential element for most organisms which must be obtained from
      the local environment. In the case of pathogenic bacteria, this fundamental
      element must be acquired from the fluids and tissues of the infected host. A
      variety of systems have evolved in bacteria for efficient acquisition of host
      bound Fe. The gram-negative bacterium Bordetella avium, upon colonization of the
      avian upper respiratory tract, produces a disease in birds that has striking
      similarity to whooping cough, a disease caused by the obligate human pathogen
      Bordetella pertussis. We describe a B. avium Fe utilization locus comprised of
      bhuR and six accessory genes (rhuIR and bhuSTUV). Genetic manipulations of B.
      avium confirmed that bhuR, which encodes a putative outer membrane heme receptor,
      mediates efficient acquisition of Fe from hemin and hemoproteins (hemoglobin,
      myoglobin, and catalase). BhuR contains motifs which are common to bacterial heme
      receptors, including a consensus FRAP domain, an NPNL domain, and two TonB boxes.
      An N-terminal 32-amino-acid segment, putatively required for rhuIR-dependent
      regulated expression of bhuR, is present in BhuR but not in other bacterial heme
      receptors. Two forms of BhuR were observed in the outer membrane of B. avium: a
      91-kDa polypeptide consistent in size with the predicted mature protein and a
      smaller 82-kDa polypeptide which lacks the 104 amino acids found at the N
      terminus of the 91-kDa form. A mutation in hemA was engineered in B. avium to
      demonstrate that the bacterium transports heme into the cytoplasm in a BhuR
      dependent manner. The role of BhuR in virulence was established in turkey poults
      by use of a competitive-infection model.

PMID- 12228264
TI  - Characterization of a novel intracellularly activated gene from Salmonella
      enterica serovar typhi.
AB  - A Salmonella enterica serovar Typhi gene that is selectively up-regulated upon
      bacterial invasion of eukaryotic cells was characterized. The open reading frame
      encodes a 298-amino-acid hydrophobic polypeptide (30.8 kDa), which is predicted
      to be an integral membrane protein with nine membrane-spanning domains. The
      protein is closely related (87 to 94% reliability) to different transport and
      permease systems. Gene expression under laboratory conditions was relatively
      weak; however, sevenfold induction was observed in a high-osmolarity medium (300
      mM NaCl). The growth pattern in a laboratory medium of a serovar Typhi strain Ty2
      derivative containing a 735-bp in-frame deletion in this gene, named gaiA (for
      gene activated intracellularly), was not affected. In contrast, the mutant was
      partially impaired in intracellular survival in murine peritoneal macrophages, as
      well as in human monocyte-derived macrophages. However, in the case of human
      macrophages, this survival defect was modest and evident only at late infection
      times (24 h). Despite the distinct intracellular survival kinetics displayed in
      macrophages of different species, the gaiA null mutant was significantly affected
      in its potential to trigger apoptosis in both murine and human macrophages.
      Provision of the gaiA gene in trans resulted in complementation of these
      phenotypes. Interestingly, the absence of a functional gaiA gene caused a marked
      attenuation in the mouse mucin model, as shown by the increase (3 orders of
      magnitude) in the 50% lethal dose of the mutant strain over that of the parental
      strain Ty2 (P </= 0.05). Altogether, these data indicate that the product encoded
      by the gaiA gene is required for triggering apoptosis and bacterial survival
      within murine macrophages, which is consistent with the in vivo results obtained
      in the mouse mucin model. However, gaiA was not required for initial
      intracellular survival in human cells, indicating that its role in the natural
      host might be more complex than is suggested by the studies performed in the
      murine system.

PMID- 12228265
TI  - Selective accumulation of mature asexual stages of Plasmodium falciparum-infected
      erythrocytes in the placenta.
AB  - A feature of malaria in pregnancy is accumulation of P. falciparum-infected
      erythrocytes (IEs) in the placenta, which is associated with adverse outcomes for
      mothers and infants. Infection appears to involve parasite adhesion to molecules
      such as chondroitin sulfate A, hyaluronic acid, and immunoglobulins. In vitro,
      adhesion is predominantly a property of mature asexual forms of IEs; however,
      adhesion of immature or ring forms has recently been reported. We have assessed
      the parasitemia and developmental stages of IEs in the placenta by examination of
      placental blood and histological sections with comparison to parasites in the
      peripheral blood from the same individuals. Approximately 90% of IEs in the
      placenta were mature forms. Compared to peripheral blood, the placental
      parasitemia was 10-fold higher and the density of mature IEs was over 200-fold
      higher. By contrast, the average peripheral and placental ring-stage parasitemias
      were not significantly different. In 2 of 14 cases, the density of ring forms was
      higher in placental than in peripheral blood. These findings demonstrate
      prominent selective accumulation of mature asexual-stage IEs but infrequent
      accumulation of ring stages in the placental blood spaces, consistent with an
      important role for mature-stage IE adhesion.

PMID- 12228266
TI  - Identification and characterization of lpfABCC'DE, a fimbrial operon of
      enterohemorrhagic Escherichia coli O157:H7.
AB  - The mechanisms underlying the adherence of Escherichia coli O157:H7 and other
      enterohemorrhagic E. coli (EHEC) strains to intestinal epithelial cells are
      poorly understood. We have identified a chromosomal region (designated
      lpfABCC'DE) in EHEC O157:H7 containing six putative open reading frames that was
      found to be closely related to the long polar (LP) fimbria operon (lpf) of
      Salmonella enterica serovar Typhimurium, both in gene order and in conservation
      of the deduced amino acid sequences. We show that lpfABCC'DE is organized as an
      operon and that its expression is induced during the exponential growth phase.
      The lpf genes from EHEC strain EDL933 were introduced into a nonfimbriated (Fim(
      )) E. coli K-12 strain, and the transformed strain produced fimbriae as
      visualized by electron microscopy and adhered to tissue culture cells. Anti-LpfA
      antiserum recognized a ca. 16-kDa LpfA protein when expressed under regulation of
      the T7 promoter system. The antiserum also cross-reacted with the LP fimbriae in
      immunogold electron microscopy and Western blot experiments. Isogenic E. coli
      O157:H7 lpf mutants derived from strains 86-24 and AGT300 showed slight
      reductions in adherence to tissue culture cells and formed fewer microcolonies
      compared with their wild-type parent strains. The adherence and microcolony
      formation phenotypes were restored when the lpf operon was introduced on a
      plasmid. We propose that LP fimbriae participate in the interaction of E. coli
      O157:H7 with eukaryotic cells by assisting in microcolony formation.

PMID- 12228267
TI  - Increased expression of clumping factor and fibronectin-binding proteins by hemB
      mutants of Staphylococcus aureus expressing small colony variant phenotypes.
AB  - Small colony variants (SCVs) of Staphylococcus aureus are slow-growing
      subpopulations that cause persistent and relapsing infections. The altered
      phenotype of SCV can arise from defects in menadione or hemin biosynthesis, which
      disrupt the electron transport chain and decrease ATP concentrations. With SCVs,
      virulence is altered by a decrease in exotoxin production and susceptibility to
      various antibiotics, allowing their intracellular survival. The expression of
      bacterial adhesins by SCVs is poorly documented. We tested fibrinogen- and
      fibronectin-mediated adhesion of a hemB mutant of S. aureus 8325-4 that is
      defective for hemin biosynthesis and exhibits a complete SCV phenotype. In this
      strain, adhesion to fibrinogen and fibronectin was significantly higher than that
      of its isogenic, normally growing parent and correlated with the increased
      surface display of these adhesins as assessed by flow cytometry. Real-time
      quantitative reverse transcription-PCR demonstrated increased expression of clfA
      and fnb genes by the hemB mutant compared to its isogenic parent. The influence
      of the hemB mutation on altered adhesin expression was confirmed by showing
      complete restoration of the wild-type adhesive phenotype in the hemB mutant,
      either by complementing with intact hemB or by supplementing the growth medium
      with hemin. Increased surface display of fibrinogen and fibronectin adhesins by
      the hemB mutation occurred independently from agr, a major regulatory locus of
      virulence factors in S. aureus. Both agr-positive and agr-lacking hemB mutants
      were also more efficiently internalized by human embryonic kidney cells than were
      their isogenic controls, presumably because of increased surface display of their
      fibronectin adhesins.

PMID- 12228268
TI  - Fimbrial ghf gene cluster of genital strains of Haemophilus spp.
AB  - We analyzed the LKP fimbrial gene clusters of six piliated strains of a cryptic
      genospecies of Haemophilus isolated from the genital tracts of adult patients
      (five strains) and from an infected neonate. In a group of 19 genital strains,
      LKP-like genes have been found in only these 6 strains. In addition to the ghfA,
      ghfD, and ghfE genes previously described, we characterized two genes, designated
      ghfB and ghfC, encoding the putative chaperone and assembly platform proteins.
      All six strains had a complete and unique LKP-like gene cluster consisting of the
      five genes ghfA to ghfE, homologous to genes hifA to hifE of Haemophilus
      influenzae. The sequences of the coding and intergenic regions of the ghf
      clusters of the six strains were remarkably homologous. Unlike hif clusters,
      which are inserted between purE and pepN, the ghf cluster was inserted between
      purK and pepN on the chromosome. Analysis of the flanking regions of the ghf
      cluster identified a large deletion, identical in the 5' end regions of all
      strains, including the whole purE gene and much of the purK gene. Ultrastructural
      observations, an attempt at enriching LKP fimbriae, and hemagglutination
      experiments demonstrated that none of the strains had LKP-type fimbriae.
      Nevertheless, reverse transcription (RT)-PCR showed that ghf genes were
      transcribed in four of the six strains. Sequencing of the intergenic ghfA-ghfB
      regions, including the ghf gene promoters, showed that the absence of transcripts
      in the remaining two strains was due to a decrease in the number of TA repeats (4
      or 9 repeats rather than 10) between the -10 and -35 boxes of the two overlapping
      and divergent promoters. The other four strains, which had ghf transcripts, had
      the optimal 10 TA repeats (one strain) or 5 repeats associated with putative
      alternative -35 boxes (three strains). The absence of 10 repeated palindromic
      sequences of 44 or 45 nucleotides upstream of ghfB induces an increased
      instability of mRNA, as quantified by real-time RT-PCR, and may explain why the
      LKP fimbrial gene cluster is not expressed in these strains.

PMID- 12228269
TI  - Epitope mapping of the immunodominant antigen TB10.4 and the two homologous
      proteins TB10.3 and TB12.9, which constitute a subfamily of the esat-6 gene
      family.
AB  - The human T-cell recognition of the low-molecular-mass culture filtrate antigen
      TB10.4 was evaluated in detail. The molecule was strongly recognized by T cells
      isolated from tuberculosis (TB) patients and from BCG-vaccinated donors. The
      epitopes on TB10.4 were mapped with overlapping peptides and found to be
      distributed throughout the molecule. The broadest response was found in TB
      patients, whereas the response in BCG-vaccinated donors was focused mainly toward
      a dominant epitope located in the N terminus (amino acids 1 to 18). The gene
      encoding TB10.4 was found to belong to a subfamily within the esat-6 family that
      consists of the three highly homologous proteins TB10.4, TB10.3, and TB12.9
      (Rv0288, Rv3019c, and Rv3017c, respectively). Southern blot analysis combined
      with database searches revealed that the three members of the TB10.4 family were
      present only in strains of the Mycobacterium tuberculosis complex, including BCG,
      and M. kansasii, whereas other atypical mycobacteria had either one (M. avium, M.
      intracellulare, and M. marinum) or none (M. scrofulaceum, M. fortuitum, and M.
      szulgai) of the genes. The fine specificity of the T-cell response to the three
      closely related esat-6 family members was markedly different, with only a few
      epitopes shared between the molecules. Minimal differences in the amino acid
      sequence translated into large differences in recognition by T cells and
      secretion of gamma interferon. In general, the peptides from TB10.4 stimulated
      the largest responses, but epitopes unique to both TB10.3 and TB12.9 were found.
      The relevance of the findings for TB vaccine development and as a potential
      mechanism for immune evasion is discussed.

PMID- 12228270
TI  - Role of RegM, a homologue of the catabolite repressor protein CcpA, in the
      virulence of Streptococcus pneumoniae.
AB  - As part of a study of virulence gene regulation in Streptococcus pneumoniae, we
      have identified a gene encoding a homologue of the staphylococcal catabolite
      control protein CcpA in the pneumococcal genome sequence. The pneumococcal
      protein, designated RegM, has significant similarity to members of the LacI/GalR
      family of bacterial regulatory proteins. S. pneumoniae D39 derivatives with
      insertion-duplication or deletion mutations in regM were significantly attenuated
      in virulence with respect to the wild-type strain. In defined media containing
      either sucrose or lactose as sole carbon sources, the in vitro growth rates of
      D39 and the regM mutants were essentially the same. However, in the presence of
      galactose the regM mutants grew significantly faster than the wild-type strain,
      whereas growth rates were significantly lower in the presence of glucose or
      maltose. These data are consistent with the involvement of regM in the catabolism
      of carbohydrates in S. pneumoniae. RegM was a repressor of both alpha-glucosidase
      and beta-galactosidase activities in S. pneumoniae, but unlike the situation in
      certain other bacteria, it does not mediate the repression of these enzymes by
      glucose. The observed attenuation in virulence was not attributable to poorer
      growth of the regM mutants in mouse blood ex vivo, but nevertheless, the mutants
      were rapidly cleared from the blood of infected mice in vivo. The regM mutation
      had no apparent impact on expression of several confirmed pneumococcal virulence
      proteins, but studies employing a lacZ transcriptional fusion construct indicated
      that mutation of regM resulted in a significant reduction in transcription of the
      capsular polysaccharide biosynthesis locus (cps). Thus, regM is the first gene
      outside of the cps locus to be implicated in regulation of capsular gene
      expression.

PMID- 12228271
TI  - Interplay between protective and inhibitory antibodies dictates the outcome of
      experimentally disseminated Candidiasis in recipients of a Candida albicans
      vaccine.
AB  - Mice immunized with heat-inactivated, whole yeast-form cells (Y cells) of Candida
      albicans developed intense, specific humoral and cell-mediated immune responses.
      However, they were modestly protected against a lethal challenge by the fungus,
      and their sera did not confer passive protection upon nonimmunized animals.
      Surprisingly, this immune serum conferred an elevated degree of passive
      protection to normal and SCID mice when preadsorbed on whole C. albicans cells.
      After adsorption, no antibodies specific to mannoprotein (MP)-rich extracts or
      secretions were detected by indirect enzyme-linked immunosorbent assay and no
      serum reaction with the fungal cell surface was seen in immunofluorescence
      assays. However, this serum had totally preserved the level of other antibodies,
      in particular those reacting with beta-1,3 and beta-1,6 glucan (GG). The
      hypothesis that anti-GG antibodies contributed to the passive protection was
      suggested by the following circumstantial evidence: (i) mice immunized with C.
      albicans cells treated with dithiothreitol and protease (YDP cells), which
      exposed GG on their surfaces and generated anti-GG but not anti-MP antibodies,
      were substantially protected against a lethal fungus challenge; (ii) the sera,
      and their immunoglobulin fractions, of mice immunized with YDP cells transferred
      protection to nonimmune animals; and (iii) this passive protection was
      substantially abolished by preadsorption on GG but not on intact cells. Overall,
      our findings demonstrate that some anti-Candida antibodies can block the
      protective potential of immune serum, a potential to which anti-GG antibodies
      appear to contribute. Our observations may also help explain why subjects with
      elevated anti-Candida antibody titers, inclusive of anti-MP and anti-GG
      antibodies, remain nonetheless susceptible to invasive candidiasis.

PMID- 12228272
TI  - Mycobacterium bovis BCG vaccination augments interleukin-8 mRNA expression and
      protein production in guinea pig alveolar macrophages infected with Mycobacterium
      tuberculosis.
AB  - Alveolar macrophages are likely the first cell type to encounter Mycobacterium
      tuberculosis in a pulmonary infection, resulting in the production of chemokines.
      In order to evaluate this response, alveolar macrophages harvested from
      nonvaccinated and Mycobacterium bovis BCG-vaccinated guinea pigs were infected in
      vitro with live M. tuberculosis H37Ra or H37Rv (multiplicity of infection, 1:1)
      or cultured with lipopolysaccharide (10 micro g/ml) for 3, 12, and 24 h.
      Interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) mRNA
      expression was determined by real-time PCR. Culture supernatants were assayed for
      guinea pig IL-8 protein by using a human IL-8 enzyme-linked immunosorbent assay
      kit. Alveolar macrophages harvested from BCG-vaccinated guinea pigs produced
      significantly more mRNA and protein for IL-8 than alveolar macrophages harvested
      from nonvaccinated guinea pigs at 12 and 24 h poststimulation or postinfection.
      Infection with attenuated M. tuberculosis (H37Ra) stimulated alveolar macrophages
      isolated from BCG-vaccinated guinea pigs to produce significantly more IL-8 mRNA
      than did alveolar macrophages infected with a virulent strain (H37Rv) at 12 and
      24 h postinfection. Significant MCP-1 mRNA production was also detected in
      stimulated or infected alveolar macrophages; however, prior vaccination did not
      significantly affect levels of MCP-1 mRNA. Alveolar macrophages isolated from BCG
      vaccinated guinea pigs produced significantly more IL-8 mRNA and protein when
      stimulated for 24 h with heat-killed H37Ra, heat-killed H37Rv, and H37Rv cell
      wall, but not mannose-capped lipoarabinomannan (ManLAM), than did cells
      stimulated with media alone. These observations indicate that prior vaccination
      may alter very early events in the M. tuberculosis-infected lung.

PMID- 12228273
TI  - Influence of intravenous anesthesia on mucosal and systemic antibody responses to
      nasal vaccines.
AB  - Inhalation of antigens may stimulate the immune system by way of the upper as
      well as the lower airways. We have shown that at least 1,000 times more live
      pneumococci were recovered from pulmonary tissue after being presented as drops
      of a liquid suspension onto the nares of anesthetized mice compared to the number
      of bacteria recovered from animals that were not anesthetized in the course of
      the challenge. Mice that were similarly immunized intranasally by inhalation of
      three different nonreplicating particulate vaccine formulations, i.e., a
      meningococcal outer membrane vesicle (OMV) vaccine, a formalin-inactivated whole
      virus influenza (INV) vaccine, and the INV vaccine with OMVs as a mucosal
      adjuvant, during general intravenous anesthesia developed concentrations of
      vaccine-specific serum immunoglobulin G (IgG) antibodies that were four to nine
      times higher than in mice that were fully awake during immunizations. The
      concentrations of IgA antibodies in serum were also higher in anesthetized than
      in nonanesthetized mice and correlated positively with the corresponding levels
      of serum IgG antibodies in the anesthetized but not in the nonanesthetized mice.
      In saliva and feces, however, the concentrations of IgA antibodies were equally
      high whether or not the animals were dormant during immunizations. The results
      indicate that intrapulmonary antigen presentation, as a part of an intranasal
      immunization strategy, is of importance for systemic but not for mucosal antibody
      responses. A major portion of IgA antibodies in serum may thus be derived from
      nonmucosal sites.

PMID- 12228274
TI  - Purification and characterization of a second immunoreactive mannoprotein from
      Cryptococcus neoformans that stimulates T-Cell responses.
AB  - Although T-cell responses are known to be critical for effective host defenses
      against the fungal pathogen Cryptococcus neoformans, the antigens that stimulate
      protective responses are poorly characterized but are thought to be comprised, at
      least in part, of mannoproteins. Recently, we created a panel of murine CD4(+)-T
      cell hybridomas that react with C. neoformans antigens. A mannoprotein antigen,
      MP98, that stimulated one of the hybridomas was purified, and the gene encoding
      MP98 was cloned. In the present study, the cryptococcal antigen, MP88, that
      stimulated a second T-cell hybridoma, X5A3, to secrete interleukin-2 was
      characterized. MP88 was purified from supernatants of glass bead-disrupted C.
      neoformans by anion-exchange and hydrophobic interaction chromatography. A single
      band with an apparent molecular mass of 88 kDa was resolved by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and subjected to partial internal
      amino acid sequencing. The gene encoding MP88 was cloned and sequenced. MP88
      features a C-terminal serine/threonine-rich region, which presumably serves as a
      site for extensive O glycosylation, followed by a putative
      glycosylphosphatidylinositol anchor site. A search of C. neoformans genomic
      databases revealed that MP88 shares this feature with at least 11 other genes,
      including MP98. The mannoprotein nature of MP88 was established based upon the
      capacity of (i) the mannoprotein fraction of C. neoformans supernatants to
      stimulate X5A3 and (ii) mannosylated ligands to competitively inhibit this
      stimulation. Thus, a second cryptococcal mannoprotein has been identified which
      stimulates T-cell responses and is a vaccine candidate.

PMID- 12228275
TI  - Gene expression profiling of peripheral blood mononuclear cells from cattle
      infected with Mycobacterium paratuberculosis.
AB  - A bovine-specific cDNA microarray system containing 721 unique leukocyte
      expressed sequence tags (ESTs) and amplicons representing known genes was used to
      compare gene expression profiles of peripheral blood mononuclear cells (PBMCs)
      from clinical and subclinical Johne's disease-positive Holstein cows (n = 2 per
      group). Stimulation of PBMCs from clinically infected cows with Mycobacterium
      paratuberculosis tended to decrease expression of 83 genes (fold change, >1.5).
      Of these 83 genes, 16 displayed significant down regulation across both clinical
      cows (P < 0.1), including genes encoding microspherule protein 1, fibroblast
      growth factor, and the Lyn B protein kinase. Only eight genes from PBMCs of
      clinically infected cows exhibited a modest up regulation following stimulation
      with M. paratuberculosis, including those encoding bovine CD40L, gamma
      interferon, interleukin-10 (IL-10), and tissue inhibitor of matrix
      metalloproteinases (TIMP) 4. In contrast, stimulation of PBMCs from subclinically
      infected cows with M. paratuberculosis tended to up regulate expression of 71
      genes representing 68 unique transcripts. Of these, 11 genes showed significant
      up regulation (fold change, >1.5; P < 0.1) across both animals, including those
      encoding bovine CD40L, several matrix metalloproteinases, and SPARC (secreted
      protein, acidic and rich in cystine). Repression of gene expression was also
      observed in PBMCs from the subclinical cows, with 16 genes being significantly
      down regulated (fold change, >1.5; P < 0.1) across both animals, including those
      encoding the bovine orthologs of cytochrome oxidase subunit III, IL-1 receptor
      type I, and fibrinogen-like 2 protein. Only one clone, representing an unknown
      bovine EST, was similarly down regulated in PBMCs from both the clinical and
      subclinical cows. Thus, the most prominent change induced by exposure of PBMCs
      from clinical cows to M. paratuberculosis in vitro tended to be repression of
      gene expression, while changes in similarly treated PBMCs from subclinical cows
      was balanced between gene activation and repression. Comparison of gene
      expression profiles between PBMCs from clinical and uninfected (control) cows
      stimulated with the general mitogen concanavalin A were highly similar (overall r
      = 0.84), suggesting that M. paratuberculosis-induced gene repression in
      clinically infected cow PBMCs was not due to a general failure of the immune
      response in these animals.

PMID- 12228276
TI  - Representational difference analysis between Afa/Dr diffusely adhering
      Escherichia coli and nonpathogenic E. coli K-12.
AB  - Diffusely adhering Escherichia coli strains harboring Afa/Dr adhesins (Afa/Dr
      DAEC) have been associated with diarrhea and urinary tract infections (UTIs). The
      present work is the first extensive molecular study of a Afa/Dr DAEC strain using
      the representational difference analysis technique. We have searched for DNA
      sequences present in strain C1845, recovered from a diarrheagenic child, but
      absent from a nonpathogenic K-12 strain. Strain C1845 harbors part of a
      pathogenicity island (PAI(CFT073)) and several iron transport systems found in
      other E. coli pathovars. We did not find genes encoding factors known to subvert
      host cell proteins, such as type III secretion system or effector proteins.
      Several C1845-specific sequences are homologous to putative virulence genes or
      show no homology with known sequences, and we have analyzed their distribution
      among Afa/Dr and non-Afa/Dr clinical isolates and among strains from the E. coli
      Reference Collection. Three C1845-specific sequences (MO30, S109, and S111) have
      a high prevalence (77 to 80%) among Afa/Dr strains and a low prevalence (12 to
      23%) among non-Afa/Dr strains. In addition, our results indicate that strain
      IH11128, an Afa/Dr DAEC strain recovered from a patient with a UTI, is
      genetically closely related to strain C1845.

PMID- 12228277
TI  - Identification of two distinct subpopulations of Leishmania major-specific T
      helper 2 cells.
AB  - It is widely accepted that a strong Th2 response is responsible for nonhealing
      Leishmania major infections in BALB/c mice. This Th2 response has been thoroughly
      documented by measuring the levels of Th2 cytokines produced by CD4(+) T cells
      present in the lymphoid organs by enzyme-linked immunosorbent assay and PCR.
      However, the cytokine profile of L. major-specific Th2 cells has never been
      determined. In this study, we used the recently described Th2 marker T1/ST2 to
      characterize Th2 cells during the course of nonhealing L. major infection. We
      analyzed the intracellular cytokine profile of CD4(+) T1/ST2(+) T cells and
      showed that they clearly displayed a Th2 phenotype, as they expressed interleukin
      4 (IL-4), IL-10, and IL-5. In addition, we detected another population of Th2
      cells among the CD4(+) T1/ST2(-) T cells that expressed IL-4 and IL-10 but
      excluded IL-5. In summary, we show here that two type 2 subpopulations are
      present in the lymphoid organs of L. major-infected BALB/c mice; Th2 cells from
      both subsets expressed IL-4 and IL-10, but they could be distinguished by their
      expression of IL-5 and T1/ST2.

PMID- 12228279
TI  - Cholera toxin and heat-labile enterotoxin activate human monocyte-derived
      dendritic cells and dominantly inhibit cytokine production through a cyclic AMP
      dependent pathway.
AB  - Cholera toxin (CT) and heat-labile enterotoxin (LT) are powerful mucosal
      adjuvants whose cellular targets and mechanism of action are unknown. There is
      emerging evidence that dendritic cells (DC) are one of the principal cell types
      that mediate the adjuvant effects of these toxins in vivo. Here we investigate
      the effects of CT and LT on the maturation of human monocyte-derived DC (MDDC) in
      vitro. We found that an enzymatically active A domain is necessary for both CT
      and LT to induce the maturation of MDDC and that this activation is strictly
      cyclic AMP (cAMP) dependent. ADP-ribosylation-defective derivatives of these
      toxins failed to induce maturation of MDDC, whereas dibutyryl-cyclic-3',5'-AMP
      and Forskolin mimic the maturation of MDDC induced by CT and LT. In addition, an
      inhibitor of cAMP-dependent kinases, Rp-8-Br-cAMPs, blocked the ability of CT,
      LT, and Forskolin to activate MDDC. CT, LT, dibutyryl-cyclic-3',5'-AMP, and
      Forskolin also dominantly inhibit interleukin 12 and tumor necrosis factor alpha
      production by MDDC in the presence of saturating concentrations of
      lipopolysaccharide. Taken together, these results show that the effects of CT and
      LT on MDDC are mediated by cAMP.

PMID- 12228278
TI  - Major histocompatibility complex class II DR-restricted memory CD4(+) T
      lymphocytes recognize conserved immunodominant epitopes of Anaplasma marginale
      major surface protein 1a.
AB  - Native major surface protein 1 (MSP1) of Anaplasma marginale, composed of
      covalently associated MSP1a and MSP1b proteins, stimulates protective immunity in
      cattle against homologous and heterologous strain challenge. Protective immunity
      against pathogens in the family Anaplasmataceae involves both CD4(+) T cells and
      neutralizing immunoglobulin G. Thus, an effective vaccine should contain both
      CD4(+) T- and B-lymphocyte epitopes that will elicit strong memory responses upon
      infection with homologous and heterologous strains. Previous studies demonstrated
      that the predominant CD4(+) T-cell response in MSP1 vaccinates is directed
      against the MSP1a subunit. The present study was designed to identify conserved
      CD4(+) T-cell epitopes in MSP1a presented by a broadly represented subset of
      major histocompatibility complex (MHC) class II molecules that would be suitable
      for inclusion in a recombinant vaccine. Transmembrane protein prediction analysis
      of MSP1a from the Virginia strain revealed a large hydrophilic domain (HD),
      extending from amino acids (aa) 1 to 366, and a hydrophobic region extending from
      aa 367 to 593. The N terminus (aa 1 to 67) includes one 28-aa form A repeat and
      one 29-aa form B repeat, which each contain an antibody neutralization-sensitive
      epitope [Q(E)ASTSS]. In MSP1 vaccinates, recombinant MSP1a HD (aa 1 to 366)
      stimulated recall proliferative responses that were comparable to those against
      whole MSP1a excluding the repeat region (aa 68 to 593). Peptide mapping
      determined a minimum of five conserved epitopes in aa 151 to 359 that stimulated
      CD4(+) T cells from cattle expressing DR-DQ haplotypes common in Holstein
      Friesian breeds. Peptides representing three epitopes (aa 231 to 266, aa 270 to
      279, and aa 290 to 319) were stimulatory for CD4(+) T-cell clones and restricted
      by DR. A DQ-restricted CD4(+) T-cell epitope, present in the N-terminal form B
      repeat (VSSQSDQASTSSQLG), was also mapped using T-cell clones from one vaccinate.
      Although form B repeat-specific T cells did not recognize the form A repeat
      peptide (VSSQS_EASTSSQLG), induction of T-cell anergy by this peptide was ruled
      out. The presence of multiple CD4(+) T-cell epitopes in the MSP1a HD, in addition
      to the neutralization-sensitive epitope, supports the testing of this immunogen
      for induction of protective immunity against A. marginale challenge.

PMID- 12228280
TI  - Effect of omp10 or omp19 deletion on Brucella abortus outer membrane properties
      and virulence in mice.
AB  - The distinctive properties of Brucella outer membrane have been considered to be
      critical for Brucella sp. virulence. Among the outer membrane molecules possibly
      related to these properties, Omp10 and Omp19 are immunoreactive outer membrane
      lipoproteins. Moreover, these proteins of Brucella could constitute a new family
      of outer membrane proteins specifically encountered in the family RHIZOBIACEAE:
      We evaluated the impact of omp10 or omp19 deletion on Brucella abortus outer
      membrane properties and virulence in mice. The omp10 mutant was dramatically
      attenuated for survival in mice and was defective for growth in minimal medium
      but was not impaired in intracellular growth in vitro, nor does it display clear
      modification of the outer membrane properties. Significantly fewer brucellae were
      recovered from the spleens of mice infected with the omp19 mutant than from those
      of mice infected with the parent strain at 4 and 8 weeks postinfection. The omp19
      mutant exhibited an increase in sensitivity to the polycation polymyxin B and to
      sodium deoxycholate. These results indicate that inactivation of the omp19 gene
      alters the outer membrane properties of B. abortus.

PMID- 12228281
TI  - Genetic immunization elicits antigen-specific protective immune responses and
      decreases disease severity in Trypanosoma cruzi infection.
AB  - Immunity to Trypanosoma cruzi requires elicitation of humoral and cell-mediated
      immune responses to extracellular trypomastigotes and intracellular amastigotes.
      In this study, the effectiveness of the T. cruzi trans-sialidase family (ts)
      genes ASP-1, ASP-2, and TSA-1 as genetic vaccines was assessed. Immunization of
      mice with plasmids encoding ASP-1, ASP-2, or TSA-1 elicited poor antigen-specific
      cytotoxic-T-lymphocyte (CTL) activity and T. cruzi-specific antibody responses.
      Codelivery of interleukin-12 and granulocyte-macrophage colony-stimulating factor
      plasmids with antigen-encoding plasmids resulted in a substantial increase in CTL
      activity and antibody production and in increased resistance to T. cruzi
      infection. In pooled results from two to four experiments, 30 to 60% of mice
      immunized with antigen-encoding plasmids and 60 to 80% of mice immunized with
      antigen-encoding plasmids plus cytokine adjuvants survived a lethal challenge
      with T. cruzi. In comparison, 90% of control mice injected with empty plasmid DNA
      died during the acute phase of infection. However, the pool of three ts genes
      provided no greater protection than the most effective single gene (ASP-2) either
      with or without coadministration of cytokine plasmids. Importantly, the extent of
      tissue parasitism, inflammation, and associated tissue damage in skeletal muscles
      during the chronic phase of T. cruzi infection in mice immunized with antigen
      encoding plasmids plus cytokine adjuvants was remarkably reduced compared to mice
      immunized with only cytokine adjuvants or empty plasmid DNA. These results
      identify new vaccine candidates and establish some of the methodologies that
      might be needed to develop effective vaccine-mediated control of T. cruzi
      infection. In addition, this work provides the first evidence that prophylactic
      genetic immunization can prevent the development of Chagas' disease.

PMID- 12228282
TI  - Differential responses of bovine macrophages to Mycobacterium avium subsp.
      paratuberculosis and Mycobacterium avium subsp. avium.
AB  - Mycobacterium avium subsp. paratuberculosis and Mycobacterium avium subsp. avium
      are antigenically and genetically similar organisms; however, they differ in
      their virulence for cattle. M. avium subsp. paratuberculosis causes a chronic
      intestinal infection leading to a chronic wasting disease termed paratuberculosis
      or Johne's disease, whereas M. avium subsp. avium causes only a transient
      infection. We compared the response of bovine monocyte-derived macrophages to
      ingestion of M. avium subsp. paratuberculosis and M. avium subsp. avium organisms
      by determining organism survival, superoxide and nitric oxide production, and
      expression of the cytokines tumor necrosis factor alpha (TNF-alpha), gamma
      interferon (IFN-gamma), interleukin-8 (IL-8), IL-10, IL-12, and granulocyte
      monocyte colony-stimulating factor (GM-CSF). Unlike M. avium subsp.
      paratuberculosis, macrophages were able to kill approximately half of the M.
      avium subsp. avium organisms after 96 h of incubation. This difference in killing
      efficiency was not related to differences in nitric oxide or superoxide
      production. Compared to macrophages activated with IFN-gamma and
      lipopolysaccharide, macrophages incubated with M. avium subsp. paratuberculosis
      showed greater expression of IL-10 and GM-CSF (all time points) and IL-8 (72 h)
      and less expression of IL-12 (72 h), IFN-gamma (6 h), and TNF-alpha (6 h). When
      cytokine expression by macrophages incubated with M. avium subsp.
      paratuberculosis was compared to those of macrophages incubated with M. avium
      subsp. avium, M. avium subsp. paratuberculosis-infected cells showed greater
      expression of IL-10 (6 and 24 h) and less expression of TNF-alpha (6 h).
      Therefore, the combination of inherent resistance to intracellular degradation
      and suppression of macrophage activation through oversecretion of IL-10 may
      contribute to the virulence of M. avium subsp. paratuberculosis in cattle.

PMID- 12228283
TI  - Cytokine profiles of patients infected with Mycobacterium ulcerans and unaffected
      household contacts.
AB  - Mycobacterium ulcerans, the cause of Buruli ulcer, is an environmental
      mycobacterium with a distinct geographic distribution. The reasons why only some
      individuals who are exposed to M. ulcerans develop ulcers are not known but are
      likely to reflect individual differences in the immune response to infections
      with this bacterium. In this study, we investigated cytokine profiles of
      peripheral blood mononuclear cells (PBMC) from 23 Buruli ulcer patients and 25
      household contacts in a region of Australia where Buruli ulcer is endemic. The
      results showed that following stimulation with M. ulcerans or Mycobacterium bovis
      BCG, PBMC from Buruli ulcer patients mounted a Th2-type response, which was
      manifested by the production of mRNA for interleukin 4 (IL-4), IL-5, IL-6, and IL
      10, whereas unaffected contacts responded mainly with the Th1 cytokines gamma
      interferon (IFN-gamma) and IL-12. For example, mRNA for IL-4 was detected in 18
      of 23 patients but in only 3 of 25 control subjects (P < 0.0001). By contrast,
      PBMC from 21 of 25 unaffected individuals produced IFN-gamma compared with 3 of
      23 patients (P < 0.0001). IFN-gamma release following stimulation with
      mycobacteria was markedly reduced in affected subjects. Frequencies of antibodies
      to M. ulcerans in serum samples from affected and unaffected subjects were
      similar, indicating that many of the control subjects had been exposed to this
      bacterium. Together, these findings suggest that a Th1-type immune response to M.
      ulcerans may prevent the development of Buruli ulcer in people exposed to M.
      ulcerans, but a Th-2 response does not.

PMID- 12228284
TI  - Bacterial artificial chromosome-based comparative genomic analysis identifies
      Mycobacterium microti as a natural ESAT-6 deletion mutant.
AB  - Mycobacterium microti is a member of the Mycobacterium tuberculosis complex that
      causes tuberculosis in voles. Most strains of M. microti are harmless for humans,
      and some have been successfully used as live tuberculosis vaccines. In an attempt
      to identify putative virulence factors of the tubercle bacilli, genes that are
      absent from the avirulent M. microti but present in human pathogen M.
      tuberculosis or Mycobacterium bovis were searched for. A minimal set of 50
      bacterial artificial chromosome (BAC) clones that covers almost all of the genome
      of M. microti OV254 was constructed, and individual BACs were compared to the
      corresponding BACs from M. bovis AF2122/97 and M. tuberculosis H37Rv. Comparison
      of pulsed-field gel-separated DNA digests of BAC clones led to the identification
      of 10 regions of difference (RD) between M. microti OV254 and M. tuberculosis. A
      14-kb chromosomal region (RD1(mic)) that partly overlaps the RD1 deletion in the
      BCG vaccine strain was missing from the genomes of all nine tested M. microti
      strains. This region covers 13 genes, Rv3864 to Rv3876, in M. tuberculosis,
      including those encoding the potent ESAT-6 and CFP-10 antigens. In contrast,
      RD5(mic), a region that contains three phospholipase C genes (plcA to -C), was
      missing from only the vole isolates and was present in M. microti strains
      isolated from humans. Apart from RD1(mic) and RD5(mic) other M. microti-specific
      deleted regions have been identified (MiD1 to MiD3). Deletion of MiD1 has removed
      parts of the direct repeat region in M. microti and thus contributes to the
      characteristic spoligotype of M. microti strains.

PMID- 12228285
TI  - Tissue selectivity of interferon-stimulated gene expression in mice infected with
      Dam(+) versus Dam(-) Salmonella enterica serovar Typhimurium strains.
AB  - The host interferon (IFN) system plays an important role in protection against
      microbial infections. Salmonella enterica serovar Typhimurium is highly virulent
      in the mouse model, whereas mutants that lack DNA adenine methylase (Dam(-)) are
      highly attenuated and elicit fully protective immune responses against murine
      typhoid fever. We examined the expression of IFN-responsive genes in several
      mouse tissues following infection with Dam(+) or Dam(-) Salmonella. Infection of
      mice with Dam(+) Salmonella resulted in the induction of host genes known to be
      indicators of IFN bioactivity and regulated by either IFN-alpha/beta (Mx1) or IFN
      gamma (class II transactivator protein [CIITA] and inducible nitric oxide
      synthase [iNOS]) or by both IFN-alpha/beta and IFN-gamma (RNA-specific adenosine
      deaminase [ADAR1] and RNA-dependent protein kinase [PKR]) in a tissue-specific
      manner compared to uninfected animals. Since the Mx1 promoter is IFN-alpha/beta
      specific and the Mx1 gene is not inducible directly by IFN-gamma, these data
      suggest a role of IFN-alpha/beta in the host response to Salmonella infection.
      Mice infected with Dam(-) Salmonella showed reduced expression of the same set of
      IFN-stimulated genes (ISGs) as that observed after infection with wild-type
      Salmonella. The reduced capacity to induce ISGs persisted in Dam(-)-vaccinated
      mice after challenge with the virulent (Dam(+)) strain. Finally, although no Dam(
      ) organisms were recovered from the liver or spleen after oral infection of mice,
      ADAR, PKR, Mx, and CIITA expression levels were elevated in these tissues
      relative to those in uninfected mice, suggestive of the distant action of a
      signaling molecule(s) in the activation of ISG expression.

PMID- 12228286
TI  - Enhanced immunogenicity of pneumococcal surface adhesin A by genetic fusion to
      cytokines and evaluation of protective immunity in mice.
AB  - Immunization of mice with pneumococcal surface adhesin A (PsaA) emulsified in
      complete Freund's adjuvant (CFA) provides protection against systemic infection
      with Streptococcus pneumoniae. Because the use of CFA is not acceptable in
      humans, we sought to develop alternative means of enhancing the immunogenicity of
      protein antigens of potential use in pneumococcal vaccines. We designed a series
      of genetic constructs in which coding sequences for PsaA were linked to sequences
      encoding either murine interleukin-2 (mIL-2), mIL-4, or two copies of an
      immunostimulatory nonapeptide derived from mIL-1beta. The PsaA-cytokine
      constructs were cloned and expressed in Escherichia coli. Mice immunized twice
      with PsaA-IL-2, or PsaA-IL-4 responded with PsaA-specific antibody production
      comparable in magnitude to that of mice primed with PsaA in CFA and boosted with
      PsaA in incomplete Freund's adjuvant (PsaA-Adj). Antibodies elicited by PsaA-Adj
      were predominantly of the immunoglobulin G1 (IgG1) subclass, while PsaA-IL-2 and
      PsaA-IL-4 elicited substantial amounts of IgG2a in addition to IgG1. Mice
      immunized with PsaA-Adj or PsaA-IL-4 were partially protected against
      intraperitoneal challenge with virulent S. pneumoniae (30% overall survival
      beyond 15 days postchallenge). Mice immunized with PsaA and no adjuvant or PsaA
      IL-2 exhibited 0 or 5% survival rates, respectively, following challenge. In
      contrast, mice immunized twice with capsular polysaccharide were 100% protected.
      The modest levels of protection seen in mice immunized with PsaA and its more
      immunogenic derivatives may be explained in part by the relative inaccessibility
      of antibody to PsaA on the surface of encapsulated S. pneumoniae.

PMID- 12228287
TI  - Beneficial or deleterious effects of a preexisting hypersensitivity to bacterial
      components on the course and outcome of infection.
AB  - Priming with heat-killed Propionibacterium acnes enhances the sensitivity of mice
      to lipopolysaccharide (LPS) and other biologically active bacterial components.
      We show that P. acnes priming has protective and deleterious effects on a
      subsequent serovar Typhimurium infection. It may result in a complete protection
      or prolonged survival, or it may accelerate mortality of the infected mice,
      depending on the number of serovar Typhimurium bacteria administered and on the
      degree of LPS hypersensitivity at the time of infection. Both effects of P. acnes
      induced hypersensitivity are mediated by gamma interferon (IFN-gamma) and are
      based on a differential activation of the innate immune mechanisms which
      recognize and react against the LPS present in infecting bacteria. In P. acnes
      primed mice null for LPS-binding protein (LBP(-/-) mice), the impaired LPS
      recognition, due to the absence of LBP, resulted in a higher resistance to
      serovar Typhimurium infection. A similar P. acnes priming of mice had a
      protective, but no deleterious effect on a subsequent L. monocytogenes infection.
      This effect was IFN-gamma dependent but independent of LBP.

PMID- 12228288
TI  - The human complement regulator factor H binds pneumococcal surface protein PspC
      via short consensus repeats 13 to 15.
AB  - The innate ability of Streptococcus pneumoniae to resist complement activation
      and complement-mediated phagocytosis may be a direct consequence of the ability
      of the bacteria to bind components of the complement regulatory system. One such
      component, factor H (fH), is a crucial fluid-phase negative regulator of the
      alternative pathway of complement and is utilized by a number of pathogenic
      organisms to resist complement attack. The pneumococcal surface protein C (PspC
      [also known as CbpA] and SpsA) has been shown to bind fH, although the exact
      binding site within one or more of the 20 short consensus repeats (SCRs) of the
      molecule is not known. The purpose of the current study was to map specific SCRs
      on fH responsible for this binding. Initial experiments utilizing type 2
      pneumococcal strain D39 and its isogenic PspC-negative derivative (D39/pspC
      mutant) showed that fH binding was PspC dependent. A purified recombinant protein
      derivative of PspC that lacked the proline-rich region (PspCDeltaPro) had a
      reduced binding efficiency for fH, thereby directly showing the importance of
      this region for the fH interaction. We have specifically shown by inhibition
      experiments that SCRs responsible for heparin and C3b binding of fH are not
      involved in binding PspC and the interaction between fH and PspC is largely
      hydrophobic, since no inhibition was observed in the presence of high
      concentrations of NaCl. Construction of SCR proteins encompassing the whole fH
      molecule showed that SCRs 8 to 15 (SCR 8-15) mediated binding to PspC. Further
      localization experiments revealed that SCR 13 and SCR 15 were required for full
      binding, although partial binding was retained when either SCR was removed.

PMID- 12228289
TI  - Characterization of P40, a cytadhesin of Mycoplasma agalactiae.
AB  - An immunodominant protein, P40, of Mycoplasma agalactiae was analyzed genetically
      and functionally. The gene encoding P40 was cloned from type strain PG2,
      sequenced, submitted to point mutagenesis in order to convert mycoplasma-specific
      TGA(Trp) codon to the universal TGG(Trp) codon, and subsequently expressed in
      Escherichia coli. Nucleotide sequence-derived amino acid sequence comparisons
      revealed a similarity of P40 to the adhesin P50 of Mycoplasma hominis and to
      protein P89 of Spiroplasma citri, which is expected to be involved in adhesion.
      The amino acid sequence of P40 revealed a recognition site for a signal peptidase
      and strong antigenic and hydrophilic motifs in the C-terminal domain. Triton X
      114 phase partitioning confirmed that P40 is a membrane protein. Fab fragments of
      antibodies directed against recombinant purified P40 significantly inhibited
      adherence of M. agalactiae strains PG2 to lamb joint synovial cells LSM 192. Sera
      taken sequentially from sheep infected with PG2 revealed that P40 induced a
      strong and persistent immune response that gave strong signals on immunoblots
      containing recombinant P40 even 3 months after infection. The gene encoding P40
      was present in a single copy in all of the 26 field strains of M. agalactiae
      analyzed and was not detected in closely related mycoplasma species. P40 was
      expressed as a protein with an apparent molecular mass of 37 kDa on sodium
      dodecyl sulfate-acrylamide gels by all M. agalactiae strains except for serotype
      C strains, which showed nonsense mutations in their p40 genes.

PMID- 12228290
TI  - Oral immunization with a Salmonella enterica serovar typhi vaccine induces
      specific circulating mucosa-homing CD4(+) and CD8(+) T cells in humans.
AB  - The kinetics and homing characteristics of T-cell responses in humans after
      mucosal immunizations have not been well characterized. Therefore, we have
      investigated the magnitude and duration of such responses as well as the homing
      receptor expression of antigen-specific peripheral blood T cells by using an oral
      model vaccine, i.e., the live, attenuated Salmonella enterica serovar Typhi
      vaccine (Ty21a). Eight volunteers were each given three doses of the vaccine 2
      days apart, and blood samples, from which CD4(+) and CD8(+) T cells were selected
      by the use of magnetic beads, were collected before vaccination and at regular
      intervals thereafter. To purify the potentially antigen-specific gut-homing T
      cells, CD45RA(-) integrin beta(7)(+) cells were further sorted by flow cytometry.
      The sorted cells were then stimulated in vitro with the serovar Typhi vaccine
      strain, and the proliferation of cells and the cytokine production were measured.
      Following vaccination, there was a large increase in both the proliferation of
      and the gamma interferon (IFN-gamma) production by blood T cells stimulated with
      the vaccine strain. The responses were seen among both CD4(+) and CD8(+) T cells,
      although the CD8(+) cells produced the largest amounts of IFN-gamma. Peak
      responses were seen 7 to 14 days after the onset of vaccination. Furthermore,
      most of the IFN-gamma produced by both CD4(+) and CD8(+) cells emanated from
      cells with the potential to home to mucosal tissues, as the integrin beta(7)
      expressing memory T cells produced around 10-fold more IFN-gamma than the
      remaining populations. In conclusion, we demonstrate that oral vaccination with a
      live oral bacterial vaccine induces antigen-specific CD4(+) and CD8(+) memory T
      cells, almost all of which express the gut-homing integrin beta(7).

PMID- 12228291
TI  - Virulent Mycobacterium fortuitum restricts NO production by a gamma interferon
      activated J774 cell line and phagosome-lysosome fusion.
AB  - The virulence of different isolates of Mycobacterium has been associated with two
      morphologically distinguishable colonial variants: opaque (SmOp) and transparent
      (SmTr). In this report we used an in vitro assay to compare macrophage (Mphi)
      responses to SmOp and SmTr Mycobacterium fortuitum variants, taking advantage of
      the fact that these variants were derived from the same isolate. Cells
      preactivated or not with gamma interferon (IFN-gamma) were infected with SmOp or
      SmTr M. fortuitum. We showed that SmOp and SmTr induced different levels of
      nitric oxide (NO) production by IFN-gamma-stimulated Mphi. Indeed, the amount of
      IFN-gamma-induced NO production by J774 cells was 4.8 to 9.0 times higher by SmOp
      (23.1 to 37.7 micro M) compared to SmTr infection (3.9 to 4.8 micro M) (P =
      0.0332), indicating that virulent SmTr bacilli restricted NO production. In
      addition, IFN-gamma-induced NO production by Mphi was higher when correlated with
      reduction of only avirulent SmOp bacillus viability. SNAP (S-nitroso-N-acetyl-DL
      penicillamine)-induced NO production did not modify SmTr viability, indicating
      its resistance to nitrogen radicals. Electron microscopy studies were performed
      to evaluate the capacity of phagosomes to fuse with lysosomes labeled with bovine
      serum albumin-colloidal gold particles. By 24 h postinfection, 69% more phagosome
      containing SmOp variant had fused with lysosomes compared to the SmTr-induced
      phagosomes. In conclusion, these data indicate that virulent SmTr bacilli may
      escape host defense by restricting IFN-gamma-induced NO production, resisting
      nitrogen toxic radicals, and limiting phagosome fusion with lysosomes.

PMID- 12228292
TI  - N-acylhomoserine lactones undergo lactonolysis in a pH-, temperature-, and acyl
      chain length-dependent manner during growth of Yersinia pseudotuberculosis and
      Pseudomonas aeruginosa.
AB  - In gram-negative bacterial pathogens, such as Pseudomonas aeruginosa and Yersinia
      pseudotuberculosis, cell-to-cell communication via the N-acylhomoserine lactone
      (AHL) signal molecules is involved in the cell population density-dependent
      control of genes associated with virulence. This phenomenon, termed quorum
      sensing, relies upon the accumulation of AHLs to a threshold concentration at
      which target structural genes are activated. By using biosensors capable of
      detecting a range of AHLs we observed that, in cultures of Y. pseudotuberculosis
      and P. aeruginosa, AHLs accumulate during the exponential phase but largely
      disappear during the stationary phase. When added to late-stationary-phase, cell
      free culture supernatants of the respective pathogen, the major P. aeruginosa [N
      butanoylhomoserine lactone (C4-HSL) and N-(3-oxododecanoyl)homoserine lactone (3
      oxo-C12-HSL)] and Y. pseudotuberculosis [N-(3-oxohexanoyl)homoserine lactone (3
      oxo-C6-HSL) and N-hexanoylhomoserine lactone (C6-HSL)] AHLs were inactivated.
      Short-acyl-chain compounds (e.g., C4-HSL) were turned over more extensively than
      long-chain molecules (e.g., 3-oxo-C12-HSL). Little AHL inactivation occurred with
      cell extracts, and no evidence for inactivation by specific enzymes was apparent.
      This AHL turnover was discovered to be due to pH-dependent lactonolysis. By
      acidifying the growth media to pH 2.0, lactonolysis could be reversed. By using
      carbon-13 nuclear magnetic resonance spectroscopy, we found that the ring opening
      of homoserine lactone (HSL), N-propionyl HSL (C3-HSL), and C4-HSL increased as pH
      increased but diminished as the N-acyl chain was lengthened. At low pH levels,
      the lactone rings closed but not via a simple reversal of the ring opening
      reaction mechanism. Ring opening of C4-HSL, C6-HSL, 3-oxo-C6-HSL, and N
      octanoylhomoserine lactone (C8-HSL), as determined by the reduction of pH in
      aqueous solutions with time, was also less rapid for AHLs with more electron
      donating longer side chains. Raising the temperature from 22 to 37 degrees C
      increased the rate of ring opening. Taken together, these data show that (i) to
      be functional under physiological conditions in mammalian tissue fluids, AHLs
      require an N-acyl side chain of at least four carbons in length and (ii) that the
      longer the acyl side chain the more stable the AHL signal molecule.

PMID- 12228293
TI  - Virulence effect of Enterococcus faecalis protease genes and the quorum-sensing
      locus fsr in Caenorhabditis elegans and mice.
AB  - The expression of two Enterococcus faecalis extracellular virulence-related
      proteins, gelatinase (GelE) and serine protease (SprE), has been shown to be
      positively regulated by the fsr quorum-sensing system. We recently developed a
      novel system for studying E. faecalis pathogenicity that involves killing of the
      nematode worm Caenorhabditis elegans and showed that an E. faecalis fsrB mutant
      (strain TX5266) exhibited attenuated killing. We explore here the role of the
      fsr/gelE-sprE locus in pathogenicity by comparing results obtained in the
      nematode system with a mouse peritonitis model of E. faecalis infection.
      Insertion mutants of fsrA (TX5240) and fsrC (TX5242), like fsrB (TX5266), were
      attenuated in their ability to kill C. elegans. A deletion mutant of gelE
      (TX5264) and an insertion mutant of sprE (TX5243) were also attenuated in C.
      elegans killing, although to a lesser extent than the fsr mutants.
      Complementation of fsrB (TX5266) with a 6-kb fragment containing the entire fsr
      locus restored virulence in both the nematode and the mouse peritonitis models.
      The fsr mutants were not impaired in their ability to colonize the nematode
      intestine. These data show that extracellular proteases and the quorum-sensing
      fsr system are important for E. faecalis virulence in two highly divergent hosts:
      nematodes and mice.

PMID- 12228294
TI  - Interleukin-4 receptor alpha chain and STAT6 signaling inhibit gamma interferon
      but not Th2 cytokine expression within schistosome granulomas.
AB  - Compared to wild-type (WT) mice, schistosome granulomas in Stat6 knockout (KO)
      mice lacked eosinophils and had Th1 features. Interleukin-4 (IL-4) acts through
      Stat6 in assisting Th2 cell development. The importance of Stat6 for Th2-cell
      development within schistosome granulomas had not been explored. Therefore we
      studied gamma interferon (IFN-gamma), IL-4, and IL-5 production in granulomas
      from Stat6 KO and WT mice. Dispersed granuloma cells from Stat6 KO and WT mice
      made similar amounts of IL-4 and IL-5. Only Stat6 KO granuloma cells released IFN
      gamma. Granuloma T cells contained most of the IL-4, IL-5, and IFN-gamma mRNA and
      secreted these cytokines. In Stat6 KO mice, 16.6% of the granuloma cells were
      CD4(+). Of these, 10.7% stained for IFN-gamma and/or IL-4 by intracytoplasmic
      flow analysis. Few CD4(-) T cells stained positively. The IL-4-producing T cells
      did not stain for DX5 or with labeled alpha-GalCer CD1d tetramer, suggesting an
      absence of NK T cells. Thus, conventional Th cells in Stat6 KO granulomas produce
      IFN-gamma and Th2 cytokines. Stat6 limits IFN-gamma production but is unnecessary
      for Th2-cell development or localization within the granuloma.

PMID- 12228296
TI  - Genetic analysis of a Cryptosporidium parvum human genotype 1 isolate passaged
      through different host species.
AB  - Cryptosporidium parvum TU502, a genotype 1 isolate of human origin, was passaged
      through three different mammalian hosts, including humans, pigs, and calves. It
      was confirmed to be genotype 1 by PCR-restriction fragment length polymorphism
      analysis of the Cryptosporidium oocyst wall protein gene, direct sequencing of
      PCR fragments of the small subunit rRNA and beta-tubulin genes, and
      microsatellite analysis. This isolate was shown to be genetically stable when
      passaged through the three mammalian species, with no evidence of the emergence
      of new subpopulations as observed by a genotype-specific PCR assay. TU502 oocysts
      from different sources failed to infect gamma interferon knockout mice, a
      characteristic of genotype 1 isolates. The genotypic and phenotypic
      characterization of TU502 is significant since it is the isolate selected to
      sequence the genome of C. parvum genotype 1 and is currently used in several
      research projects including human volunteer studies.

PMID- 12228295
TI  - Legionella pneumophila feoAB promotes ferrous iron uptake and intracellular
      infection.
AB  - In order to determine the role of ferrous iron transport in Legionella
      pathogenesis, we identified and mutated the feoB gene in virulent Legionella
      pneumophila strain 130b. As it is in Escherichia coli, the L. pneumophila feoB
      gene was contained within a putative feoAB operon. L. pneumophila feoB insertion
      mutants exhibited decreased ferrous but not ferric iron uptake compared to the
      wild type. Growth on standard buffered charcoal yeast extract agar or buffered
      yeast extract broth was unaffected by the loss of L. pneumophila FeoB. However,
      the L. pneumophila feoB mutant had a reduced ability to grow on buffered charcoal
      yeast extract agar with a reduced amount of its usual iron supplementation, a
      phenotype that could be complemented by the addition of feoB in trans. In
      unsupplemented buffered yeast extract broth, the feoB mutant also had a growth
      defect, which was further exacerbated by the addition of the ferrous iron
      chelator, 2,2'-dipyridyl. The feoB mutant was also 2.5 logs more resistant to
      streptonigrin than wild-type 130b, confirming its decreased ability to acquire
      iron during extracellular growth. Decreased replication of the feoB mutant was
      noted within iron-depleted Hartmannella vermiformis amoebae and human U937 cell
      macrophages. The reduced intracellular infectivity of the feoB mutant was
      complemented by the introduction of a plasmid containing feoAB. The L.
      pneumophila feoB gene conferred a modest growth advantage for the wild type over
      the mutant in a competition assay within the lungs of A/J mice. Taken together,
      these results indicate that L. pneumophila FeoB is a ferrous iron transporter
      that is important for extracellular and intracellular growth, especially in iron
      limited environments. These data represent the first evidence for the importance
      of ferrous iron transport for intracellular replication by a human pathogen.

PMID- 12228297
TI  - Secreted metalloprotease gene family of Microsporum canis.
AB  - Keratinolytic proteases secreted by dermatophytes are likely to be virulence
      related factors. Microsporum canis, the main agent of dermatophytosis in dogs and
      cats, causes a zoonosis that is frequently reported. Using Aspergillus fumigatus
      metalloprotease genomic sequence (MEP) as a probe, three genes (MEP1, MEP2, and
      MEP3) were isolated from an M. canis genomic library. They presented a quite-high
      percentage of identity with both A. fumigatus MEP and Aspergillus oryzae neutral
      protease I genes. At the amino acid level, they all contained an HEXXH consensus
      sequence, confirming that these M. canis genes (MEP genes) encode a zinc
      containing metalloprotease gene family. Furthermore, MEP3 was found to be the
      gene encoding a previously isolated M. canis 43.5-kDa keratinolytic
      metalloprotease, and was successfully expressed as an active recombinant enzyme
      in Pichia pastoris. Reverse transcriptase nested PCR performed on total RNA
      extracted from the hair of M. canis-infected guinea pigs showed that at least
      MEP2 and MEP3 are produced during the infection process. This is the first report
      describing the isolation of a gene family encoding potential virulence-related
      factors in dermatophytes.

PMID- 12228298
TI  - Relationship of the glyoxylate pathway to the pathogenesis of Cryptococcus
      neoformans.
AB  - Functional genomics has become a major focus in the study of microbial
      pathogenesis. This study used a functional genomic tool, differential display
      reverse transcription-PCR, to identify a transcriptional profile of Cryptococcus
      neoformans cells as they produced meningitis in an immunosuppressed host. This
      serial global gene expression during infection allowed for the identification of
      up- and down-regulated genes during infection. During this profiling, a single
      gene for the enzyme isocitrate lyase (ICL1) was found to be up regulated at 1
      week of infection in a rabbit meningitis model and during a time of maximum host
      cellular response. The finding suggested that this enzyme and the glyoxylate
      shunt pathway are important to this yeast's energy production during infection.
      However, site-directed icl1 mutants had no apparent virulence defect in two
      animal models and no growth defect within macrophages. These observations suggest
      that although the yeast responded to a certain environmental cue(s) by an
      increase in ICL1 expression during infection, this gene was not necessary for
      progression of a C. neoformans infection. Compounds that specifically target only
      ICL1 are unlikely to cripple C. neoformans growth in vivo.

PMID- 12228299
TI  - Modulation of an interleukin-12 and gamma interferon synergistic feedback
      regulatory cycle of T-cell and monocyte cocultures by Porphyromonas gingivalis
      lipopolysaccharide in the absence or presence of cysteine proteinases.
AB  - Interleukin 12 (IL-12) is an efficient inducer and enhancer of gamma interferon
      (IFN-gamma) production by both resting and activated T cells. There is evidence
      that human monocytes exposed to IFN-gamma have enhanced ability to produce IL-12
      when stimulated with lipopolysaccharide (LPS). In this study, it was demonstrated
      that LPS from the oral periodontal pathogen Porphyromonas gingivalis stimulated
      monocytes primed with IFN-gamma to release IL-12, thereby enhancing IFN-gamma
      accumulation in T-cell populations. P. gingivalis LPS was shown to enhance IL-12
      induction of IFN-gamma in T cells in a manner independent from TNF-alpha
      contribution. The levels of T-cell IL-12 receptors were not affected by P.
      gingivalis LPS and played only a minor role in the magnitude of the IFN-gamma
      response. These data suggest that LPS from P. gingivalis establishes an
      activation loop with IL-12 and IFN-gamma with potential to augment the production
      of inflammatory cytokines in relation to the immunopathology of periodontitis. We
      previously reported that the major cysteine proteinases (gingipains) copurifying
      with LPS in this organism were responsible for reduced IFN-gamma accumulation in
      the presence of IL-12. However, the addition of the gingipains in the presence of
      LPS resulted in partial restoration of the IFN-gamma levels. In the destructive
      periodontitis lesion, release of gingipains from the outer membrane (OM) of P.
      gingivalis could lead to the downregulation of Th1 responses, while gingipain
      associated with LPS in the OM or in OM vesicles released from the organism could
      have net stimulatory effects.

PMID- 12228300
TI  - The divergently transcribed Streptococcus parasanguis virulence-associated fimA
      operon encoding an Mn(2+)-responsive metal transporter and pepO encoding a zinc
      metallopeptidase are not coordinately regulated.
AB  - The study of how bacteria respond to and obtain divalent metal ions provides
      insight into the regulation of virulence factors in the host environment.
      Regulation of metal permease operons in gram-positive bacteria may involve the
      binding of metal-responsive repressors to palindromic domains in their control
      regions. The Streptococcus parasanguis fimA operon, which encodes an ATP-binding
      cassette (ABC) transporter system with sequence homology to the LraI family of
      metal transporters, possesses a palindromic regulatory region with high homology
      to that of the Streptococcus gordonii ScaR binding domain. Mapping of the
      promoter and regulatory regions of fimA and the divergently transcribed pepO
      gene, which encodes a zinc metalloendopeptidase, indicated that their promoter
      and regulatory elements overlap. fimA had one transcriptional start site, whereas
      pepO had three. Analysis of truncated versions of the pepO promoter suggested
      that all three transcriptional start sites are functional. Analysis of promoter
      activity under various environmental conditions indicated that the fimA operon
      promoter and the pepO promoter are not coordinately regulated. The fimA operon is
      responsive to changes in Mn(2+) concentration, but the pepO promoter is not. A S.
      parasanguis fimA mutant showed a growth deficiency under conditions of limiting
      Mn(2+). This deficiency was not alleviated by compensation with either Mg(2+) or
      Fe(3+). Wild-type S. parasanguis could take up Mn(2+) and Fe(3+), while the fimA
      mutant showed a marked reduction in this ability. These data suggested that FimA
      is a component of a metal transporter system capable of transporting both Mn(2+)
      and Fe(3+). FimA expression itself was shown to be responsive to Mn(2+)
      concentration, but not to availability of Fe(3+) or Mg(2+).

PMID- 12228301
TI  - Combined treatment with interleukin-12 and indomethacin promotes increased
      resistance in BALB/c mice with established Leishmania major infections.
AB  - Following infection of susceptible BALB/c mice with Leishmania major, early
      production of interleukin-4 (IL-4) is associated with the development of a
      nonprotective Th2 response and the development of progressive disease. Treatment
      of mice with IL-12 at the time of infection can promote the activation of a
      protective Th1 response; however, IL-12 treatment of mice with established
      infections has little effect on the progress of lesion development. This may be
      due to a down-regulation of the IL-12 receptor beta2 chain (IL-12Rbeta2) that
      accompanies the expansion of IL-4-producing Th2 cells. We have examined whether
      prostaglandins function to regulate in vivo responsiveness to IL-12. Mice treated
      with indomethacin are responsive to treatment with exogenous IL-12 through at
      least the first 2 weeks of infection and, unlike control mice treated with IL-12,
      develop an enhanced Th1-type response associated with increased enhanced
      resistance to infection. Cells from indomethacin-treated mice also exhibit
      enhanced production of gamma interferon (IFN-gamma) following in vitro
      stimulation with IL-12. Although in vivo indomethacin treatment did not appear to
      influence IL-12 production in infected mice, cells from indomethacin-treated mice
      did express higher levels of IL-12Rbeta2, suggesting that prostaglandins may play
      a role in the loss of IL-12 responsiveness observed during nonhealing L. major
      infections.

PMID- 12228302
TI  - Characterization of a murine model of Ureaplasma urealyticum pneumonia.
AB  - Ureaplasma urealyticum respiratory tract colonization in preterm infants has been
      associated with a high incidence of pneumonia and the development of
      bronchopulmonary dysplasia. However, study of this human pathogen has been
      hampered by the absence of animal models. We have developed the first juvenile
      mouse model of Ureaplasma pneumonia and characterized the histopathology during
      the month following inoculation. C3H/HeN mice were inoculated intratracheally
      with a mouse-adapted clinical Ureaplasma isolate (biovar 2) or sham inoculated
      with 10B broth. Culture of lung homogenates and PCR of DNA from bronchoalveolar
      lavage fluid (BAL) confirmed the presence of Ureaplasma in 100% of inoculated
      animals at 1 day, 60% at 2 days, 50% at 3 days, and 25% at 7 and 14 days.
      Ureaplasma was undetectable 28 days postinoculation. There were marked changes in
      BAL and interstitial-cell composition with increased number of polymorphonuclear
      leukocytes 1 to 2 days and 14 days postinoculation and macrophages at 2 and 14
      days postinoculation. The Ureaplasma infection caused a persistent focal loss of
      airway ciliated epithelium and a mild increase in interstitial cellularity. There
      were no differences in BAL protein concentration during the first 28 days,
      suggesting that pulmonary vascular endothelial barrier integrity remained intact.
      Comparison of BAL cytokine and chemokine concentrations revealed low levels of
      tumor necrosis factor alpha (TNF-alpha) at 3 days and monocyte chemoattractant
      protein 1 at 7 days in Ureaplasma-infected mice but a trend toward increased TNF
      alpha at 14 days and increased granulocyte-macrophage colony-stimulating factor
      and interleukin-10 at 28 days. These data suggest that Ureaplasma alone may cause
      limited inflammation and minimal tissue injury in the early phase of infection
      but may promote a mild chronic inflammatory response in the later phase of
      infection (days 14 to 28), similar to the process that occurs in human newborns.

PMID- 12228303
TI  - Identification of a streptolysin S-associated gene cluster and its role in the
      pathogenesis of Streptococcus iniae disease.
AB  - Streptococcus iniae causes meningoencephalitis and death in cultured fish species
      and soft-tissue infection in humans. We recently reported that S. iniae is
      responsible for local tissue necrosis and bacteremia in a murine subcutaneous
      infection model. The ability to cause bacteremia in this model is associated with
      a genetic profile unique to strains responsible for disease in fish and humans
      (J. D. Fuller, D. J. Bast, V. Nizet, D. E. Low, and J. C. S. de Azavedo, Infect.
      Immun. 69:1994-2000, 2001). S. iniae produces a cytolysin that confers a
      hemolytic phenotype on blood agar media. In this study, we characterized the
      genomic region responsible for S. iniae cytolysin production and assessed its
      contribution to virulence. Transposon (Tn917) mutant libraries of commensal and
      disease-associated S. iniae strains were generated and screened for loss of
      hemolytic activity. Analysis of two nonhemolytic mutants identified a chromosomal
      locus comprising 9 genes with 73% homology to the group A streptococcus (GAS) sag
      operon for streptolysin S (SLS) biosynthesis. Confirmation that the S. iniae
      cytolysin is a functional homologue of SLS was achieved by PCR ligation
      mutagenesis, complementation of an SLS-negative GAS mutant, and use of the SLS
      inhibitor trypan blue. SLS-negative sagB mutants were compared to their wild-type
      S. iniae parent strains in the murine model and in human whole-blood killing
      assays. These studies demonstrated that S. iniae SLS expression is required for
      local tissue necrosis but does not contribute to the establishment of bacteremia
      or to resistance to phagocytic clearance.

PMID- 12228304
TI  - Nuclear targeting of Porphyromonas gingivalis W50 protease in epithelial cells.
AB  - Porphyromonas gingivalis is an important pathogen associated with destructive
      periodontal disease and is able to invade the epithelial cell barrier. Its
      cysteine proteases are recognized as major virulence factors, and in this study,
      we examined the interaction of the arginine-specific protease with epithelial
      cells in culture. Three cell lines (KB, HeLa, and SCC4) were incubated with
      strain W50 culture supernatant; stained with monoclonal antibody 1A1, which
      recognizes an epitope on the adhesin (beta) component of the cysteine protease
      adhesin (alpha/beta) heterodimer; and viewed using immunofluorescence microscopy.
      Within 1 h, the protease traversed the plasma membrane and was localized around
      the nucleus before becoming concentrated in the cytoplasm after 24 to 48 h. In
      contrast, the purified arginine-specific heterodimeric protease (HRgpA) rapidly
      entered the nucleus within 15 to 30 min. This nuclear targeting (i) was seen with
      active and Nalpha-p-tosyl-L-lysine chloromethyl ketone (TLCK)-inactivated HRgpA,
      indicating it was independent of the proteolytic activity; (ii) occurred at both
      4 and 37 degrees C; and (iii) failed to occur with the monomeric protease
      (RgpA(cat)), indicating the importance of the adhesin chain of the HRgpA protease
      to this process. Rapid cell entry was also observed with recombinant catalytic
      (alpha) and adhesin (beta) chains, with the latter again targeting the nuclear
      area. After 48 h of incubation with HRgpA, significant dose-dependent stimulation
      of metabolic activity was observed (measured by reduction of 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide), and a doubling of
      mitotic activity combined with the presence of apoptotic cells indicated that
      HRgpA may interfere with cell cycle control mechanisms. These effects were seen
      with both active and TLCK-inactivated protease, confirming that they were not
      dependent on proteolytic activity, and thus provide new insights into the
      functioning of this P. gingivalis protease.

PMID- 12228305
TI  - Independent translocation of two micronemal proteins in developing Plasmodium
      falciparum merozoites.
AB  - Apical membrane antigen 1 of Plasmodium falciparum (PfAMA1) contains an N
      terminal propeptide that is removed prior to the translocation of the mature
      protein onto the merozoite surface. We localized unprocessed PfAMA1 to the
      microneme organelles of the intraerythrocytic schizont. The results have
      suggested that the processed form of PfAMA1 translocates from the microneme
      compartment independently of another microneme protein, EBA175, which is also
      involved in the invasion of human erythrocytes.

PMID- 12228306
TI  - Characterization of a pore-forming cytotoxin expressed by Salmonella enterica
      serovars typhi and paratyphi A.
AB  - Cytolysin A (ClyA) is a pore-forming cytotoxic protein encoded by the clyA gene
      that has been characterized so far only in Escherichia coli. Using DNA sequence
      analysis and PCR, we established that clyA is conserved in the human-specific
      typhoid Salmonella enterica serovars Typhi and Paratyphi A and that the entire
      clyA gene locus is absent in many other S. enterica serovars, including
      Typhimurium. The gene products, designated ClyA(STy) and ClyA(SPa), show >/=90%
      amino acid identity to E. coli cytolysin A, ClyA(EC), and they are
      immunogenically related. The Salmonella proteins showed a pore-forming activity
      and are hence functional homologues to ClyA(EC). The chromosomal clyA(STy) gene
      locus was expressed at detectable levels in the serovar Typhi strains S2369/96
      and S1112/97. Furthermore, in the serovar Typhi vaccine strain Ty21a, expression
      of clyA(STy) reached phenotypic levels, as detected on blood agar plates. The
      hemolytic phenotype was abolished by the introduction of an in-frame deletion in
      the clyA(STy) chromosomal locus of Ty21a. Transcomplementation of the mutant with
      a cloned clyA(STy) gene restored the hemolytic phenotype. To our knowledge, Ty21a
      is the first reported phenotypically hemolytic Salmonella strain in which the
      genetic determinant has been identified.

PMID- 12228307
TI  - Binding of Clostridium difficile surface layer proteins to gastrointestinal
      tissues.
AB  - Clostridium difficile is the etiological agent of antibiotic-associated diarrhea,
      a potentially serious condition frequently affecting elderly hospitalized
      patients. While tissue damage is primarily induced by two toxins, the mechanism
      of gut colonization, and particularly the role of bacterial adherence to the
      mucosa, remains to be clarified. Previous studies have shown binding of C.
      difficile whole cells to cultured cell lines and suggested the existence of
      multiple adhesins, only one of which has been molecularly characterized. In this
      paper, we have investigated tissue binding of C. difficile surface layer proteins
      (SLPs), which are the predominant outer surface components and are encoded by the
      slpA gene. The adherence of C. difficile to HEp-2 cells was studied by enzyme
      linked immunosorbent assay and fluorescence-activated cell sorter analysis, which
      showed that antibodies to the high-molecular-weight (MW) SLP inhibited adherence.
      Immunohistochemical analysis of human gastrointestinal tissue sections revealed
      strong binding both to the surface epithelium lining the digestive cavities and
      to the subjacent lamina propria, while glands were negative. A similar pattern
      was observed in the mouse. By using purified recombinant SLPs, we show that
      binding is largely mediated by the high-MW SLP. By Western blotting analysis, we
      have identified two potential ligands of the C. difficile SLPs, one of which may
      be specific to the gut. By using purified extracellular matrix components
      immobilized on nitrocellulose, we also show SLP binding to collagen I,
      thrombospondin, and vitronectin, but not to collagen IV, fibronectin, or laminin.
      These results raise the possibility that the SLPs play a role both in the initial
      colonization of the gut by C. difficile and in the subsequent inflammatory
      reaction.

PMID- 12228308
TI  - Variation in the expression of a Plasmodium falciparum protein family implicated
      in erythrocyte invasion.
AB  - The PfRH protein family of Plasmodium falciparum is implicated in erythrocyte
      invasion. Here we report variations in the sequence, transcription, and protein
      expression of four different members of this family in three parasite lines, 3D7,
      T996, and FCB1. There are sequence polymorphisms in PfRH1, PfRH2a, PfRH2b, and
      PfRH3, ranging from variations across repeat regions to a 585-bp deletion in the
      3' end of PfRH2b in T996. Not all the genes are transcribed: although all members
      of the family are transcribed in 3D7 and T996, PfRH2a and PfRH2b are not
      transcribed in FCB1. The PfRH1, PfRH2a, and PfRH2b proteins are expressed in late
      schizonts and merozoites and are located in apical organelles and on the apical
      surface. However, the PfRH1 protein does not appear to be correctly targeted to
      the apex in 3D7 and T996. In contrast, the PfRH1 protein is present at the apical
      end of FCB1 merozoites, but the PfRH2a and PfRH2b proteins are undetectable. The
      apparent redundancy in the PfRH family of proteins at the level of gene number
      and sequence and the variations in transcription and protein expression may allow
      the parasite to use alternative invasion pathways.

PMID- 12228309
TI  - Candida-specific antibodies during experimental vaginal candidiasis in mice.
AB  - Protective host defense mechanisms against vaginal Candida albicans infections
      are poorly understood. Although cell-mediated immunity (CMI) is the predominant
      host defense mechanism against most mucosal Candida infections, the role of CMI
      against vaginal candidiasis is uncertain, both in humans and in an experimental
      mouse model. The role of humoral immunity is equally unclear. While clinical
      observations suggest a minimal role for antibodies against vaginal candidiasis,
      an experimental rat model has provided evidence for a protective role for Candida
      specific immunoglobulin A (IgA) antibodies. Additionally, Candida vaccination
      induced IgM and IgG3 antibodies are protective in a mouse model of vaginitis. In
      the present study, the role of infection-induced humoral immunity in protection
      against experimental vaginal candidiasis was evaluated through the quantification
      of Candida-specific IgA, IgG, and IgM antibodies in serum and vaginal lavage
      fluids of mice with primary and secondary (partially protected) infection. In
      naive mice, total, but not Candida-specific, antibodies were detected in serum
      and lavage fluids, consistent with lack of yeast colonization in mice. In
      infected mice, Candida-specific IgA and IgG antibodies were induced in serum with
      anamnestic responses to secondary infection. In lavage fluid, while Candida
      specific antibodies were detectable, concentrations were extremely low with no
      anamnestic responses in mice with secondary infection. The incorporation of
      alternative protocols-including infections in a different strain of mice,
      prolongation of primary infection prior to secondary challenge, use of different
      enzyme-linked immunosorbent assay capture antigens, and concentration of lavage
      fluid-did not enhance local Candida-specific antibody production or detection.
      Additionally, antibodies were not removed from lavage fluids by being bound to
      Candida during infection. Together, these data suggest that antibodies are not
      readily present in vaginal secretions of infected mice and thus have a limited
      natural protective role against infection.

PMID- 12228310
TI  - The Mycobacterium tuberculosis phagosome in human macrophages is isolated from
      the host cell cytoplasm.
AB  - Knowledge of whether Mycobacterium tuberculosis resides within a relatively
      impermeable membrane-bound vacuole or is free within the cytoplasm within its
      host cell is central to an understanding of the immunobiology of this
      intracellular parasite but is a matter of controversy. To explore this issue, we
      assessed the accessibility of medium-size protein molecules (Fab fragments of
      50,000 Da) to M. tuberculosis within human macrophages. We infected the
      macrophages with wild-type or green fluorescent protein-expressing M.
      tuberculosis, microinjected Fab fragments directed against a major surface
      antigen of M. tuberculosis into the host cell, and assayed the accessibility of
      the bacteria to the Fab fragments by both immunofluorescence microscopy and
      immunogold electron microscopy. Whereas microinjected intact immunoglobulin G
      molecules against cytoplasmic early endosomal antigen 1 readily stained this
      antigen, microinjected Fab fragments against M. tuberculosis did not stain the
      bacterium within its phagosome. In contrast, microinjected Fab fragments against
      Listeria monocytogenes, an intracellular bacterium known to permeabilize its
      phagosomal membrane, strongly stained this bacterium. Our study shows that M.
      tuberculosis resides in an isolated phagosome that is relatively impermeable to
      cytoplasmic constituents.

PMID- 12228311
TI  - Immortalization of human urethral epithelial cells: a model for the study of the
      pathogenesis of and the inflammatory cytokine response to Neisseria gonorrhoeae
      infection.
AB  - The primary human urethral epithelial cells developed by our laboratory have been
      immortalized by transduction with a retroviral vector expressing the human
      papillomavirus E6E7 oncogenes. Analysis of telomerase expression and comparison
      to that in primary cells revealed detectable levels in the transduced human
      urethral epithelial cells. Immortalized urethral cells could be passaged over 20
      times. Immunofluorescence microscopy studies showed that the immortalized cells
      were phenotypically similar and responded to gonococcal infection similarly to
      primary cells. Specifically, positive cytokeratin staining showed that the
      immortalized cells are keratinocytes; cell surface levels of human
      asialoglycoprotein receptor increase following gonococcal infection, and, like
      the primary cells, the immortalized urethral epithelial cells are CD14 negative.
      Using enzyme-linked immunosorbent assay, we found that interleukin-6 (IL-6) and
      IL-8 levels in primary urethral epithelial cell supernatants increase after
      challenge with N. gonorrhoeae. Likewise, the immortalized urethral epithelial
      cells produced higher levels of IL-6 and IL-8 cytokines in response to gonococcal
      infection. Cells challenged with a gonococcal lipid A msbB mutant produced
      reduced IL-6 and IL-8 levels when compared to the parent strain. Additionally,
      these data suggest that the 1291 msbB lipooligosaccharide may suppress cytokine
      induction.

PMID- 12228312
TI  - Coxiella burnetii localizes in a Rab7-labeled compartment with autophagic
      characteristics.
AB  - The obligate intracellular bacterium Coxiella burnetii, the agent of Q fever in
      humans and of coxiellosis in other animals, survives and replicates within large,
      acidified, phagolysosome-like vacuoles known to fuse homo- and heterotypically
      with other vesicles. To further characterize these vacuoles, HeLa cells were
      infected with C. burnetii phase II; 48 h later, bacteria-containing vacuoles were
      labeled by LysoTracker, a marker of acidic compartments, and accumulated
      monodansylcadaverine and displayed protein LC3, both markers of autophagic
      vacuoles. Furthermore, 3-methyladenine and wortmannin, agents known to inhibit
      early stages in the autophagic process, each blocked Coxiella vacuole formation.
      These autophagosomal features suggest that Coxiella vacuoles interact with the
      autophagic pathway. The localization and role of wild-type and mutated Rab5 and
      Rab7, markers of early and late endosomes, respectively, were also examined to
      determine the role of these small GTPases in the trafficking of C. burnetii phase
      II. Green fluorescent protein (GFP)-Rab5 and GFP-Rab7 constructs were
      overexpressed and visualized by fluorescence microscopy. Coxiella-containing
      large vacuoles were labeled with wild-type Rab7 (Rab7wt) and with GTPase
      deficient mutant Rab7Q67L, whereas no colocalization was observed with the
      dominant-negative mutant Rab7T22N. The vacuoles were also decorated by GFP
      Rab5Q79L but not by GFP-Rab5wt. These results suggest that Rab7 participates in
      the biogenesis of the parasitophorous vacuoles.

PMID- 12228313
TI  - Cellular localization of Babesia bovis merozoite rhoptry-associated protein 1 and
      its erythrocyte-binding activity.
AB  - The cellular localization of Babesia bovis rhoptry-associated protein 1 (RAP-1)
      and its erythrocyte-binding affinity were examined with anti-RAP-1 antibodies. In
      an indirect immunofluorescent antibody test, RAP-1 was detectable in all
      developmental stages of merozoites and in extracellular merozoites. In the early
      stage of merozoite development, RAP-1 appears as a dense accumulation, which
      later thins out and blankets the host cell cytoplasm, but retains a denser mass
      around newly formed parasite nuclei. The preferential accumulations of RAP-1 on
      the inner surface of a host cell membrane and bordering the parasite's outer
      surface were demonstrable by immunoelectron microscopy. An erythrocyte-binding
      assay with the lysate of merozoites demonstrated RAP-1 binding to both bovine and
      equine erythrocytes. Anti-RAP-1 monoclonal antibody 1C1 prevented the interaction
      of RAP-1 with bovine erythrocytes and significantly inhibited parasite
      proliferation in vitro. With the recombinant RAP-1, the addition of increasing
      concentrations of Ca(2+) accentuated its binding affinity with bovine
      erythrocytes. The present findings lend support to an earlier proposition of an
      erythrocytic binding role for RAP-1 expressed in B. bovis merozoites and,
      possibly, its involvement in the escape of newly formed merozoites from host
      cells.

PMID- 12228314
TI  - Isolation of Chlamydia pneumoniae clonal variants by a focus-forming assay.
AB  - Chlamydia pneumoniae is an obligate intracellular prokaryotic human pathogen that
      causes community-acquired respiratory infection and has been associated with
      atherosclerosis and cardiovascular disease. Unexpected results from genomic
      sequencing indicate that significant intrastrain polymorphism exists for some C.
      pneumoniae isolates. These polymorphisms could reflect genotypes with differing
      disease-causing characteristics. A definitive means to test this hypothesis is to
      obtain genetically homogeneous clonal populations of the pathogen and test them
      in models of infection and disease. To date, methods for cloning C. pneumoniae
      have not been reported. In this study, we describe the isolation of clonal
      variants with genetic differences in the tyrP locus from a polymorphic
      respiratory isolate, using a novel focus-forming assay. These results now allow
      investigations on the biology and pathogenesis of C. pneumoniae clonal genovars
      that could lead to new insights into the pathogenesis of this important human
      pathogen.

PMID- 12228315
TI  - Identification of the Staphylococcus aureus etd pathogenicity island which
      encodes a novel exfoliative toxin, ETD, and EDIN-B.
AB  - We identified a novel pathogenicity island in Staphylococcus aureus which
      contains open reading frames (ORFs) similar to the exfoliative toxin (ET) gene,
      glutamyl endopeptidase gene, and edin-B gene in tandem and the phage resistance
      gene, flanked by hsdM, hsdS (restriction and modification system), and IS256. The
      protein encoded by the ET-like gene showed 40, 59, and 68% amino acid sequence
      identities with exfoliative toxin A (ETA), exfoliative toxin B (ETB), and
      Staphylococcus hyicus ETB (ShETB), respectively. When injected into neonatal
      mice, the recombinant protein derived from the ET-like gene induced exfoliation
      of the skin with loss of cell-to-cell adhesion in the upper part of the epidermis
      as observed in histological examinations, just as was found in neonatal mice
      injected with ETA or ETB. Western blot analysis indicated that the recombinant
      protein is serologically distinct from ETA and ETB. Therefore, the product
      encoded by this new ORF is a new ET member produced by S. aureus and is termed
      ETD. ETD did not induce blisters in 1-day-old chickens. In the skins of mice
      injected with ETD, cell surface staining of desmoglein 1 (Dsg1), a cadherin type
      cell-to-cell adhesion molecule in desmosomes, was abolished without affecting
      that of desmoglein 3 (Dsg3). Furthermore, in vitro incubation of the recombinant
      extracellular domains of Dsg1 and Dsg3 with the recombinant protein demonstrated
      that both mouse and human Dsg1, but not Dsg3, were directly cleaved in a dose
      dependent manner. These results demonstrate that ETD and ETA induce blister
      formation by identical pathophysiological mechanisms. Clinical strains positive
      for edin-B were suggested to be clonally associated, and all edin-B-positive
      strains tested were positive for etd. Among 18 etd-positive strains, 12 produced
      ETD extracellularly. Interestingly, these strains are mainly isolated from other
      sources of infections and not from patients with bullous impetigo or
      staphylococcal scalded-skin syndrome. This strongly suggests that ETD might play
      a pathogenic role in a broader spectrum of bacterial infections than previously
      considered.

PMID- 12228316
TI  - Discrete proteolysis of focal contact and adherens junction components in
      Porphyromonas gingivalis-infected oral keratinocytes: a strategy for cell
      adhesion and migration disabling.
AB  - Adhesive interactions of cells are critical to tissue integrity. We show that
      infection with Porphyromonas gingivalis, a major pathogen in the periodontal
      disease periodontitis, interferes with both cell-matrix and cell-cell adhesion in
      the oral keratinocyte cell line HOK-16. Thus, infected cells showed reduced
      adhesion to extracellular matrix, changes in morphology from spread to rounded,
      and impaired motility on purified matrices in Transwell migration assays and
      scratch assays. Western blot analysis of P. gingivalis-challenged HOK-16 cells
      revealed proteolysis of focal contact components (e.g., focal adhesion kinase),
      adherens junction proteins (e.g., catenins), and adhesion signaling molecules
      (e.g., the tyrosine kinase SRC). Proteolysis was selective, since important
      components of adherens junctions (E-cadherin) or signaling molecules
      (extracellular signal-regulated kinases ERK1/2) were not degraded. The virulence
      factors gingipains, cysteine proteinases expressed by P. gingivalis, are likely
      responsible for this proteolytic attack, since they directly digested specific
      proteins in pull-down experiments, and their proteolytic activity was blocked by
      the cysteine proteinase inhibitor N-alpha-p-tosyl-L-lysine chloromethyl ketone
      and also by a caspase inhibitor. Proteolysis was strain dependent, such that ATCC
      33277 and 381 had high proteolytic potential, whereas W50 showed almost no
      proteolytic activity. These findings may help explain the formation of gingival
      pockets between cementum and periodontal epithelium, a hallmark of periodontitis.
      Furthermore, they illustrate a new pathogenetic paradigm of infection whereby
      bacteria may disrupt the integrity of epithelia.

PMID- 12228317
TI  - Requirement for tumor necrosis factor receptor 2 expression on vascular cells to
      induce experimental cerebral malaria.
AB  - Using tumor necrosis factor receptor type 2 (TNFR2)-deficient mice and generating
      bone marrow chimeras which express TNFR2 on either hematopoietic or
      nonhematopoietic cells, we demonstrated the requirement for TNFR2 expression on
      tissue cells to induce lethal cerebral malaria. Thus, TNFR2 on the brain
      vasculature mediates tumor necrosis factor-induced neurovascular lesions in
      experimental cerebral malaria.

PMID- 12228318
TI  - Chlamydial antigens colocalize within IncA-laden fibers extending from the
      inclusion membrane into the host cytosol.
AB  - Chlamydial IncA localizes to the inclusion membrane and to vesicular fibers
      extending away from the inclusion. Chlamydial outer membrane components, in the
      absence of developmental forms, are found within these fibers. This
      colocalization may explain how chlamydial developmental form antigens are
      localized outside of the inclusion within infected cells.

PMID- 12228319
TI  - A uropathogenicity island contributes to the pathogenicity of Escherichia coli
      strains that cause neonatal meningitis.
AB  - We report that the archetypal Escherichia coli strain C5 causing neonatal
      meningitis harbors a pathogenicity island (PAI) designated PAI I(C5) that is
      similar to the PAI II(J96) of uropathogenic E. coli J96 inserted in the leuX-tRNA
      gene. PAI-negative C5 mutants had a lower capacity than C5 to induce high-level
      bacteremia in a neonatal rat model. However, no change in their resistance to the
      bactericidal effect of serum and their capacity to cross the blood-brain barrier
      was observed.

PMID- 12228320
TI  - Macrophage-enhanced germination of Bacillus anthracis endospores requires gerS.
AB  - Germination of Bacillus anthracis Sterne and plasmidless Delta-Sterne endospores
      was dramatically enhanced in RAW264.7 macrophage-like cells, while germination of
      nonpathogenic Bacillus endospores was not. Elimination of gerS, a germinant
      receptor locus, caused a complete loss of cell-enhanced germination, implicating
      gerS in the breaking of endospore dormancy in vivo.

PMID- 12228321
TI  - A monoclonal antibody to the amebic lipophosphoglycan-proteophosphoglycan
      antigens can prevent disease in human intestinal xenografts infected with
      Entamoeba histolytica.
AB  - Entamoeba histolytica trophozoites are covered by lipophosphoglycan-peptidoglycan
      molecules which may be key virulence factors. We found that pretreatment of
      severe combined immunodeficient mice bearing human intestinal xenografts with a
      monoclonal antibody to the amebic lipophosphoglycan-peptidoglycan molecules can
      prevent or significantly reduce the human intestinal inflammation and tissue
      damage that are normally seen with E. histolytica colonic infection.

PMID- 12228322
TI  - Two predicted chemoreceptors of Helicobacter pylori promote stomach infection.
AB  - Helicobacter pylori must be motile or display chemotaxis to be able to fully
      infect mammals, but it is not known how this chemotaxis is directed. We disrupted
      two genes encoding predicted chemoreceptors, tlpA and tlpC. H. pylori mutants
      lacking either of these genes are fully motile and chemotactic in vitro and are
      as able as the wild type to infect mice when they are the sole infecting strains.
      In contrast, when mice are coinfected with the H. pylori SS1 tlpA or tlpC mutant
      and the wild type, we find more wild type than mutant after 2 weeks of
      colonization. Neither strain has an in vitro growth defect. These results suggest
      that the tlpA- and tlpC-encoded proteins assist colonization of the stomach
      environment.

PMID- 12228323
TI  - Expression and characterization of flagella in nonmotile enteroinvasive
      Escherichia coli isolated from diarrhea cases.
AB  - We report that enteroinvasive Escherichia coli (EIEC) serotypes considered to be
      nonmotile produce an unusually large (77 kDa) flagellin that is assembled into
      functional flagellum filaments that allow the bacteria to swim in modified
      motility agar. The EIEC flagellin showed N-terminal identity to most common
      enterobacterial flagellins, especially those of the E. coli H7 serotype. These
      data are important in terms of the epidemiology, evolution, and biology of EIEC.

PMID- 12228324
TI  - Identification and characterization of the N-acetylglucosamine
      glycosyltransferase gene of Haemophilus ducreyi.
AB  - Haemophilus ducreyi is the causative agent of chancroid, a sexually transmitted
      ulcerative disease. In the present study, the Neisseria gonorrhoeae lgtA
      lipooligosaccharide glycosyltransferase gene was used to identify a homologue in
      the genome of H. ducreyi. The putative H. ducreyi glycosyltransferase gene
      (designated lgtA) was cloned and insertionally inactivated, and an isogenic
      mutant was constructed. Structural studies demonstrated that the
      lipooligosaccharide isolated from the mutant strain lacked N-acetylglucosamine
      and distal sugars found in the lipooligosaccharide produced by the parental
      strain. The isogenic mutant was transformed with a recombinant plasmid containing
      the putative glycosyltransferase gene. This strain produced the
      lipooligosaccharide glycoforms produced by the parental strain, confirming that
      the lgtA gene encodes the N-acetylglucosamine glycosyltransferase.

PMID- 12228325
TI  - Differential survival of Lyme borreliosis spirochetes in ticks that feed on
      birds.
AB  - The abilities of the most common European genospecies of Borrelia burgdorferi
      sensu lato to survive blood meals taken by ticks feeding on birds were analyzed.
      A pattern of differential survival of the spirochetes in feeding ticks was
      observed. The result is consistent with the concept of selective transmission of
      Lyme borreliosis spirochetes.

PMID- 12228327
TI  - The influence of appraisals in understanding children's experiences with medical
      procedures.
AB  - OBJECTIVE: To examine the influence of cognitive appraisals on anticipatory
      anxiety, procedural distress, and postprocedural evaluations in 100 children
      (ages 8-17) undergoing esophagogastroduodenoscopy (EGD). METHOD: Children's
      knowledge about the procedure, appraisals of the procedure's aversiveness, coping
      ability, and state anxiety prior to the procedure were assessed by self-report.
      Distress during the EGD was assessed by observer ratings. Postprocedural
      evaluations were assessed by self-report 1 hour after the procedure. RESULTS:
      Structural equation modeling indicated that children who knew more about the EGD
      appraised it as less threatening, and, in turn, children who appraised the
      procedure as less threatening experienced less anxiety. Decreased anxiety was
      associated with decreased distress, which, in turn, was associated with decreased
      pain, evaluations of less aversiveness, and less negative attitudes toward future
      procedures. CONCLUSIONS: This study has implications for how children are
      prepared for EGDs and supports the utility of an appraisal-based model in
      understanding children's experiences with medical procedures.

PMID- 12228326
TI  - Production and characterization of protective human antibodies against Shiga
      toxin 1.
AB  - Hemolytic-uremic syndrome (HUS) is a serious complication which is predominantly
      associated in children with infection by Shiga toxin-producing Escherichia coli
      (STEC). By using HuMAb-Mouse (Medarex) animals, human monoclonal antibodies (Hu
      MAbs) were developed against Shiga toxin 1 (Stx1) for passive immunotherapy of
      HUS. Ten stable hybridomas comprised of fully human heavy- and light-chain
      immunoglobulin elements and secreting Stx1-specific Hu-MAbs (seven immunoglobulin
      M(kappa)() [IgM(kappa)] elements [one specific for the A subunit and six specific
      for the B subunit] and three IgG1(kappa) elements specific for subunit B) were
      isolated. Two IgM(kappa) Hu-MAbs (2D9 and 15G9) and three IgG1(kappa) Hu-MAbs
      (5A4, 10F4, and 15G2), all specific for subunit B, demonstrated marked
      neutralization of Stx1 in vitro and significant prolongation of survival in a
      murine model of Stx1 toxicosis.

PMID- 12228328
TI  - Aggression and cardiovascular response in children.
AB  - OBJECTIVE: To examine cardiovascular response as a function of children's
      aggression after controlling for the effects of known risk factors. METHOD:
      Participants were 140 children in second, fourth, and sixth grades. Teachers
      completed the Matthews Youth Test for Health, a measure that includes questions
      pertaining to children's aggression. Measures of blood pressure and heart rate
      were obtained during baseline, academic quiz, and recovery. RESULTS: Increasing
      age and body mass index were associated with increased cardiovascular responses.
      Aggressive children exhibited higher heart rates at baseline and lower heart rate
      reactivity. Aggressive children with a positive parent history of hypertension
      exhibited the greatest cardiovascular response. CONCLUSIONS: These results
      provide further support for the identification of behavioral factors that
      increase cardiovascular risk in children.

PMID- 12228329
TI  - The influence of socioeconomic status and ethnicity on adolescents' exposure to
      stressful life events.
AB  - OBJECTIVE: To test the relations between resource-based and prestige-based
      measures of socioeconomic status (SES), ethnicity, and life events that varied in
      valence, dependency on adolescent behavior, and duration. METHOD: Six measures of
      SES were administered to the parents of 148 black and white adolescents, who
      completed a measure of five mutually exclusive categories of life events.
      RESULTS: As predicted, our results suggest that having few assets and being black
      were independently related to life events exposure. Correlations between
      socioeconomic indices were not so high as to suggest redundancy, and different
      SES indicators were of importance in predicting exposure to different types of
      life events.

PMID- 12228330
TI  - Psychological differences between children with and without chronic encopresis.
AB  - OBJECTIVE: To validate a theoretical model of encopresis in terms of
      psychological factors that differentiates children with and without chronic
      encopresis and to identify scales that demonstrate these differences. METHODS:
      Eighty-six children with encopresis were compared to 62 nonsymptomatic children
      on five psychometric instruments. Differences in the mean scores and the
      percentages of children falling beyond preselected clinical thresholds were
      compared across the patient-control groups. RESULTS: Children with encopresis
      were found to have more anxiety/depression symptoms, family environments with
      less expressiveness and poorer organization, more attention difficulties, greater
      social problems, more disruptive behavior, and poorer school performance (ps =.01
      < or =.001 on 15/20 subscales). There were no differences in self-esteem. On
      those subscales where proportionately more encopretic children exceeded clinical
      thresholds, approximately 20% more of the encopretic children exceeded thresholds
      than control children. CONCLUSIONS: As a group, children with encopresis differ
      from children without encopresis on a variety of psychological parameters.
      However, only a minority of children with encopresis demonstrated clinically
      significant elevations in these parameters. Identification and treatment of such
      clinical issues may enhance treatment efficacy.

PMID- 12228331
TI  - Living with a chronic illness: a measure of social functioning for children and
      adolescents.
AB  - OBJECTIVE: To describe the development and initial psychometric evaluation of a
      measure of social functioning in children and adolescents with chronic medical
      conditions, Living with a Chronic Illness (LCI), designed to distinguish social
      difficulties related to the illness from those social difficulties associated
      with other factors (e.g., limited income). METHODS: Parents (n = 108) and youths
      (n = 115) completed the LCI, along with other psychological measures (e.g., Youth
      Self-Report). Teachers completed the Teacher Report Form and provided grade and
      absence data. Health care utilization data were obtained from medical charts.
      RESULTS: Statistical analyses supported the internal consistency and initial
      validity of LCI scores. Correlational results strongly point to the distinction
      made between illness-related and non-illness-related social difficulties and
      suggest that the LCI has some relation to existing measures (e.g., Child Behavior
      Checklist), while still providing a unique perspective on children's social
      functioning. Univariate and regression analyses revealed significant relations
      between LCI scores and health care utilization. CONCLUSIONS: These findings
      support the initial psychometric properties and clinical utility of the LCI
      scores. We discuss strengths and limitations of this study, as well as potential
      clinical applications for the LCI questionnaire.

PMID- 12228332
TI  - Predictors of PTSD in mothers of children undergoing bone marrow transplantation:
      the role of cognitive and social processes.
AB  - OBJECTIVE: To investigate the role of cognitive and social processing in
      posttraumatic stress symptoms and disorder (PTSD) among mothers of children
      undergoing bone marrow and hematopoietic stem-cell transplantation (BMT/SCT).
      METHOD: Questionnaires assessing emotional distress, BMT-related fears, and
      negative responses of family and friends were completed by 90 mothers at the time
      of the BMT infusion and 3 and 6 months post-BMT. PTSD symptoms were measured 6
      months post-BMT by both paper-and-pencil and structured interview methods.
      RESULTS: Emotional distress, BMT-related fears, and negative responses of family
      and friends assessed at the time of BMT hospitalization were predictive of later
      PTSD symptoms. None of these variables prospectively predicted a PTSD diagnosis
      as measured by the structured interview. CONCLUSIONS: Higher levels of general
      psychological distress, cognitive interpretations of the threat of the BMT for
      the child's future functioning, and negative responses of family and friends may
      place mothers at risk for post-BMT posttraumatic stress symptomatology.

PMID- 12228333
TI  - Resilience among African American adolescent mothers: predictors of positive
      parenting in early infancy.
AB  - OBJECTIVE: To use Nath et al.'s (1991) conceptual model of adolescent parenting
      to examine the relationship between resiliency factors measured shortly after
      delivery and maternal parenting behavior at 6 months. METHOD: We recruited 181
      first-time, adolescent African American mothers at delivery. Data on resiliency
      factors (maturity, self-esteem, and mother-grandmother relationships) were
      collected when infants were 1-4 weeks of age. Data on parental nurturance and
      parenting satisfaction were examined through observations and self-report at 6
      months. RESULTS: Multiple regression analyses were used to examine the
      longitudinal impact of resiliency factors on parental nurturance and parenting
      satisfaction. Maternal maturity, positive self-esteem, and positive adolescent
      mother-grandmother relationships (characterized by autonomy and mutuality) were
      associated with better parenting outcomes. Maternal parenting satisfaction was
      lowest when infants were temperamentally difficult and mothers and grandmothers
      had a confrontational relationship. CONCLUSIONS: Longitudinal associations
      between mother-grandmother relationships at delivery and parental behavior and
      satisfaction 6 months later may suggest an intergenerational transmission of
      parenting style. Recommendations are provided for intervention programs to
      enhance mother-grandmother relationships in contexts where adolescents are
      required to live with a guardian to receive government assistance.

PMID- 12228334
TI  - Pioneers in pediatric psychology: personal reflections on the evolution of
      pediatric psychology.

PMID- 12228335
TI  - Society of pediatric psychology presidential address: opportunities for health
      promotion in primary care.
AB  - OBJECTIVE: To set an agenda for health promotion in primary care settings.
      METHODS: This is a review of the scientific bases of child development as applied
      to pediatric psychology and health promotion. RESULTS: Primary care is an ideal
      setting for health promotion because there is a "hidden morbidity" of children
      with unrecognized and untreated behavioral and developmental problems that, if
      unresolved, may lead to psychiatric and physical disorders and increased use of
      the health care system. Although pediatric psychologists endorse the importance
      of health promotion, there are few examples in the literature involving pediatric
      psychologists. Recommendations are provided for a proactive agenda for health
      promotion programs involving pediatric psychologists in primary care.
      CONCLUSIONS: With conceptual homes in clinical and developmental psychology,
      expertise in theories of clinical and child development, scientific methods, and
      collaborative relationships with pediatricians, pediatric psychologists are in a
      unique position to develop and evaluate health promotion programs for use in
      primary care.

PMID- 12228336
TI  - Posttraumatic stress disorder in parents of children with newly diagnosed type 1
      diabetes.
AB  - OBJECTIVE: To determine rates of posttraumatic stress disorder (PTSD) and
      symptoms in mothers and fathers of children with newly diagnosed type 1 diabetes.
      METHODS: Parents of 38 children with newly diagnosed type 1 diabetes were
      assessed with the Posttraumatic Diagnostic Scale 6 weeks after diagnosis.
      RESULTS: Twenty-four percent of the mothers and 22% of the fathers met full
      diagnostic criteria for current PTSD. In addition, 51% of the mothers and 41% of
      the fathers met criteria for partial or subclinical PTSD. Co-occurence of PTSD in
      couples was very low. Posttraumatic stress symptomatology did not correlate with
      age and gender of the child, socioeconomic status, family structure, or length of
      hospital stay. CONCLUSIONS: The findings support applicability of a posttraumatic
      stress model for investigating the psychological impact of type 1 diabetes on
      parents.

PMID- 12228337
TI  - The Biochemistry and Molecular Biology of Isoprenoid Metabolism.

PMID- 12228338
TI  - Accumulation of 15-Kilodalton Zein in Novel Protein Bodies in Transgenic Tobacco.
AB  - Zeins, the seed storage proteins of maize, are a group of alcohol-soluble
      polypeptides of different molecular masses that share a similar amino acid
      composition but vary in their sulfur amino acid composition. They are synthesized
      on the rough endoplasmic reticulum (ER) in the endosperm and are stored in ER
      derived protein bodies. Our goal is to balance the amino acid composition of the
      methionine-deficient forage legumes by expressing the sulfur amino acid-rich 15
      kD zeins in their leaves. However, it is crucial to know whether this protein
      would be stable in nonseed tissues of transgenic plants. The major focus of this
      paper is to compare the accumulation pattern of the 15-kD zein protein with a
      vacuolar targeted seed protein, [beta]-phaseolin, in nonseed tissues and to
      determine the basis for its stability/instability. We have introduced the 15-kD
      zein and bean [beta]-phaseolin-coding sequences behind the 35S cauliflower mosaic
      virus promoter into tobacco (Nicotiana tabacum) and analyzed the protein's
      accumulation pattern in different tissues. Our results demonstrate that the 15-kD
      seed protein is stable not only in seeds but in all nonseed tissues tested,
      whereas the [beta]-phaseolin protein accumulated only in mid- and postmaturation
      seeds. Interestingly, zein accumulates in novel protein bodies both in the seeds
      and in nonseed tissues. We attribute the instability of the [beta]-phaseolin
      protein in nonseed tissues to the fact that it is targeted to protease-rich
      vacuoles. The stability of the 15-kD zein could be attributed to its retention in
      the ER or to the protease-resistant nature of the protein.

PMID- 12228339
TI  - Developmental and Hormonal Regulation of Rice [alpha]-Amylase(RAmy1A)-gusA Fusion
      Genes in Transgenic Rice Seeds.
AB  - Transgenic seeds of rice (Oryza sativa L.) were used to investigate temporal,
      spatial, and hormonal regulation of a rice [alpha]-amylase gene, RAmy1A. Two
      overlapping segments of the RAmy1A promoter were fused to the coding region of
      the bacterial reporter gene, gusA. The resulting promoter-gusA fusions, pE4/GUS (
      232 to +31) and pH4/GUS (-748 to +31), were used separately to transform rice
      protoplasts. [beta]-Glucuronidase (GUS) activity was detected in germinated
      transgenic seeds, although the two constructs showed no significant difference in
      timing or location of GUS expression. Both constructs first expressed GUS in the
      scutellar epithelium and then in the aleurone layer. Aleurone expression of GUS
      activity was strongly induced when embryoless half-seeds were treated with
      gibberellic acid. GUS expression in the aleurone layer was also suppressed by
      abscisic acid. These results indicate that the 5[prime] regulatory region from 
      232 to +31 is sufficient for temporal, spatial, and hormonal regulation of RAmy1A
      gene expression.

PMID- 12228340
TI  - L-O-Methylthreonine-Resistant Mutant of Arabidopsis Defective in Isoleucine
      Feedback Regulation.
AB  - Threonine dehydratase/deaminase (TD), the first enzyme in the isoleucine
      biosynthetic pathway, is feedback inhibited by isoleucine. By screening M2
      populations of ethyl methane sulfonate-treated Arabidopsis thaliana Columbia wild
      type seeds, we isolated five independent mutants that were resistant to L-O
      methylthreonine, an isoleucine structural analog. Growth in the mutants was 50-
      to 600-fold more resistant to L-O-methylthreonine than in the wild type. The
      resistance was due to a single, dominant nuclear gene that was denoted omr1 and
      was mapped to chromosome 3 in GM11b, the mutant line exhibiting the highest level
      of resistance. Biochemical characteristics (specific activities, Km, Vmax, and pH
      optimum) of TD in extracts from the wild type and GM11b were similar except for
      the inhibition constant of isoleucine, which was 50-fold higher in GM11b than in
      the wild type. Levels of free isoleucine were 20-fold higher in extracts from
      GM11b than in extracts from wild type. Therefore, isoleucine feedback
      insensitivity in GM11b is due to a mutant form of the TD enzyme encoded by omr1.
      The mutant allele omr1 of the line GM11b could provide a new selectable marker
      for plant genetic transformation.

PMID- 12228341
TI  - TE7, An Inefficient Symbiotic Mutant of Medicago truncatula Gaertn. cv Jemalong.
AB  - A mutagenesis program using ethylmethane sulfonate on Medicago truncatula Gaertn
      cv Jemalong, an annual, autogamous and diploid lucerne, permitted the isolation
      of a mutant (TE7) unable to establish an effective nitrogen-fixing symbiosis,
      [Nod+Fix-], with Rhizobium meliloti wild-type strains. The mutant phenotype is
      characterized by an altered infection process that leads to the formation of two
      kinds of inefficient nodules on the same root system. A certain proportion of the
      nodules are small, round, and uninfected, with infection threads limited to the
      outer root cortical cells. Others develop to a normal elongated shape and are
      infected; bacterial release occurs but the bacteria do not differentiate into
      bacteroids. The ratio of invaded to uninvaded nodules depends on the bacterial
      strain used. Throughout the infection process, certain events correlated with the
      plant defense response against pathogens can be observed: (a) the presence of
      polyphenolic compounds associated with the walls of infected cells and also with
      some parts of infection threads in the root cortex; (b) appositions on infection
      thread walls during the early stage of infection and also within the central
      tissue of infected nodules; and (c) autophagy of the plant cells that contain
      released bacteria. Genetic data suggest that the phenotype of TE7 is under
      monogenic and recessive control; this gene has been designated Mtsym1.

PMID- 12228342
TI  - Significant Changes in Cell and Chloroplast Development in Young Wheat Leaves
      (Triticum aestivum cv Hereward) Grown in Elevated CO2.
AB  - Cell and chloroplast development were characterized in young Triticum aestivum cv
      Hereward leaves grown at ambient (350 [mu]L L-1) or at elevated (650 [mu]L L-1)
      CO2. In elevated CO2, cell and chloroplast expansion was accelerated by 10 and
      25%, respectively, in the first leaf of 7-d-old wheat plants without disruption
      to the leaf developmental pattern. Elevated CO2 did not affect the number of
      chloroplasts in relation to mesophyll cell size or the linear relationship
      between chloroplast number or size and mesophyll cell size. No major changes in
      leaf anatomy or in chloroplast ultrastructure were detected as a result of growth
      in elevated CO2, but there was a marked reduction in starch accumulation. In leaf
      sections fluorescently tagged antisera were used to visualize and quantitate the
      amount of cytochrome f, the [alpha]- and [beta]-subunits of the coupling factor 1
      in ATP synthase, D1 protein of the photosystem II reaction center, the 33-kD
      protein of the extrinsic oxygen-evolving complex, subunit II of photosystem I,
      and ribulose-1,5-bisphosphate carboxylase/oxygenase. A significant finding was
      that in 10 to 20% of the mesophyll cells grown in elevated CO2 the 33-kD protein
      of the extrinsic oxygen-evolving complex of photosystem II and cytochrome f were
      deficient by 75%, but the other proteins accumulated normally.

PMID- 12228343
TI  - Polymerization of Actin from Maize Pollen.
AB  - Here we describe the in vitro polymerization of actin from maize (Zea mays)
      pollen. The purified actin from maize pollen reported in our previous paper (X.
      Liu, L.F. Yen [1992] Plant Physiol 99: 1151-1155) is biologically active. In the
      presence of ATP, KCl, and MgCl2 the purified pollen actin polymerized into
      filaments. During polymerization the spectra of absorbance at 232 nm increased
      gradually. Polymerization of pollen actin was evidently accompanied by an
      increase in viscosity of the pollen actin solution. Also, the specific viscosity
      of pollen F-actin increased in a concentration-dependent manner. The ultraviolet
      difference spectrum of pollen actin is very similar to that of rabbit muscle
      actin. The activity of myosin ATPase from rabbit muscle was activated 7-fold by
      the polymerized pollen actin (F-actin). The actin filaments were visualized under
      the electron microscope as doubly wound strands of 7 nm diameter. If cytochalasin
      B was added before staining, no actin filaments were observed. When actin
      filaments were treated with rabbit heavy meromyosin, the actin filaments were
      decorated with an arrowhead structure. These results imply that there is much
      similarity between pollen and muscle actin.

PMID- 12228344
TI  - Selection and Characterization of [alpha]-Methyltryptophan-Resistant Lines of
      Lemna gibba Showing a Rapid Rate of Indole-3-Acetic Acid Turnover.
AB  - Turnover rate is an important aspect of the regulation of plant processes by
      plant growth substances. To study turnover of indole-3-acetic acid (IAA), two
      [alpha]-methyltryptophan-resistant lines (MTR1 and MTR2) of Lemna gibba were
      generated by nitrosomethyl urea treatment of an inbred line derived from L. gibba
      G-3. In this report we describe: (a) the development of a selection system using
      this near isogenic line of L. gibba; (b) techniques for chemical mutation of the
      lines and selection for [alpha]-methyltryptophan resistance; and (c) the partial
      characterization of the selected lines. MTR lines contained 3-fold higher levels
      of anthranilate synthase activity. The enzyme in the MTR lines required higher
      levels of tryptophan for feedback inhibition. MTR lines also contained 8-fold
      higher levels of tryptophan, 3-fold higher levels of free IAA, and similar levels
      of total IAA compared to the inbred line. Turnover rates in the inbred and
      selected lines were calculated, using the first-order rate equation, based on the
      decrease over time in isotopic enrichment of I3C6-IAA introduced into L. gibba
      during a 1-h pulse period. Isotope enrichment in IAA was determined by using gas
      chromatography-mass spectrometry. Both MTR lines had an approximately 10-fold
      higher rate of IAA turnover than the parent inbred line.

PMID- 12228345
TI  - Is ATP Required for K+ Channel Activation in Vicia Guard Cells?
AB  - In vivo, K+ entry into guard cells via inward-rectifying K+ channels is
      indirectly driven by ATP via an H+-ATPase that hyperpolarizes the membrane
      potential. However, whether activation of the K+ channels of guard cells requires
      ATP remains unknown. In the present study, both whole-cell and single-channel
      patch-clamp techniques were used to address this question. Exogenous ATP, ADP,
      and adenosine-5[prime]-O-(3-thiotriphosphate) applied to the cytoplasm had no
      effect on whole-cell K+ currents of Vicia faba L. guard cells. Azide, an
      inhibitor of oxidative phosphorylation, also had no effect. However, an ATP
      scavenging system, glucose plus hexokinase, inhibited whole-cell inward K+
      currents by 30 to 40%. Single-channel results acquired from cytoplasm-free inside
      out membrane patches showed definite activation of inward K+ channels by ATP.
      Other nucleotides, such as ADP, adenosine-5[prime]-O(3-thiotriphosphate), and
      GTP, did not increase channel activity in the membrane patches. Inward K+ channel
      activity in membrane patches preactivated by exogenous ATP was inhibited by
      glucose plus hexokinase. These results suggest that a low concentration of ATP is
      required for activation of the inward K+ channels of the guard-cell plasma
      membrane. The issue of how ATP as a signal regulates these K+ channels is
      discussed.

PMID- 12228346
TI  - [beta]-Glucan Synthesis in the Cotton Fiber (IV. In Vitro Assembly of the
      Cellulose I Allomorph).
AB  - In vitro assembly of cellulose from plasma membrane extracts of the cotton
      (Gossypium hirsutum) fiber was enriched by a combination of 3-(N
      morpholino)propanesulfonic acid extraction buffer and two independent digitonin
      solubilization steps consisting of 0.05% digitonin (SE1) followed by 1% digitonin
      (SE2). Glucan synthase activity assays revealed that, although the SE2 fraction
      possessed higher activity, only 8.6% of the in vitro product survived
      acetic/nitric acid treatment. On the other hand, the SE1 fraction was less
      active, but 32.1% of the total glucan in vitro product was resistant to
      acetic/nitric acid. In vitro products synthesized from the SE1 fraction contained
      [beta]-1,3-glucan and fibrillar cellulose I, whereas the SE2 fraction produced
      [beta]-1,3-glucan and cellulose II. Both celluloses assembled in vitro were
      labeled with cellobiohydrolase I-gold complex, and the electron diffraction
      patterns of both products from SE1 and SE2 revealed cellulose I and cellulose II,
      respectively. Contamination of native cellulose was ruled out by extensive
      evidence from autoradiography of the ethanol-insoluble and acetic/nitric acid
      insoluble materials, including three different controls.

PMID- 12228347
TI  - Improved Performance of Transgenic Fructan-Accumulating Tobacco under Drought
      Stress.
AB  - Fructans are polyfructose molecules produced by approximately 15% of the
      flowering plant species. It is possible that, in addition to being a storage
      carbohydrate, fructans have other physiological roles. Owing to their solubility
      they may help plants survive periods of osmotic stress induced by drought or
      cold. To investigate the possible functional significance of fructans, use was
      made of transgenic tobacco (Nicotiana tabacum) plants that accumulate bacterial
      fructans and hence possess an extra sink for carbohydrate. Biomass production was
      analyzed during drought stress with the use of lines differing only in the
      presence of fructans. Fructan-producing tobacco plants performed significantly
      better under polyethylene-glycol-mediated drought stress than wild-type tobacco.
      The growth rate of the transgenic plants was significantly higher (+55%), as were
      fresh weight (+33%) and dry weight (+59%) yields. The difference in weight was
      observed in all organs and was particularly pronounced in roots. Under unstressed
      control conditions the presence of fructans had no significant effect on growth
      rate and yield. Under all conditions the total nonstructural carbohydrate content
      was higher in the transgenic plants. We conclude that the introduction of
      fructans in this non-fructan-producing species mediates enhanced resistance to
      drought stress.

PMID- 12228348
TI  - Phytochrome, Gibberellins, and Hypocotyl Growth (A Study Using the Cucumber
      (Cucumis sativus L.) long hypocotyl Mutant).
AB  - The possible involvement of gibberellins (GAs) in the regulation of hypocotyl
      elongation by phytochrome was examined. Under white light the tall long hypocotyl
      (lh) cucumber (Cucumis sativus L.) mutant, deficient in a type B-like
      phytochrome, shows an increased "responsiveness" (defined as response capability)
      to applied GA4 (the main endogenous active GA) compared to the wild type.
      Supplementing far-red irradiation results in a similar increase in responsiveness
      in the wild type. Experiments involving application of the precursor GA9 and of
      an inhibitor of GA4 inactivation suggest that both the GA4 activation and
      inactivation steps are phytochrome independent. Endogenous GA levels of whole
      seedlings were analyzed by combined gas chromatography-mass spectrometry using
      deuterated internal standards. The levels of GA4 (and those of GA34, the
      inactivated GA4) were lower in the lh mutant under low-irradiance fluorescent
      light compared with the wild type, similar to wild type under higher irradiance
      light during the initial hypocotyl extension phase, and higher during the phase
      of sustained growth, in which extension involved an increase in the number of
      cells in the upper region. In all cases, growth of the lh mutant was more rapid
      than that of the wild type. It is proposed that GA4 and phytochrome control cell
      elongation primarily through separate mechanisms that interact at a step close to
      the terminal response.

PMID- 12228350
TI  - Effects of Air Contact on Growth, Inorganic Carbon Sources, and Nitrogen Uptake
      by an Amphibious Freshwater Macrophyte.
AB  - Callitriche cophocarpa Sendtner is a heterophyllous amphibious macrophyte that
      produces apical rosettes of floating leaves. The importance of air contact for
      inorganic carbon and N uptake and for growth was investigated. Plants were grown
      with the floating rosette in contact with air of various humidities (10, 50, and
      >90% relative humidity) and with the submerged parts in N-free water at 350 [mu]M
      free CO2 and the roots in sediment with low or high NH3-N content. Humidity
      greatly affected the transpiration rate, whereas growth rate and N content were
      unaffected and were comparable to values measured for fully submerged shoots. Air
      contact had, however, a significant impact on growth when the free CO2
      concentration in the water was low. Thus, the growth rate of shoots with air
      contact was about 3 times faster than the rate of fully submerged shoots when
      grown at air-equilibrium concentration of dissolved free CO2 in the water (16
      [mu]M). This difference decreased with increased dissolved free CO2 concentration
      in the water, and the two shoot types grew at the same rate when the submerged
      shoots received >350 [mu]M free CO2. The quantitative importance of the floating
      rosette for total carbon uptake declined also with decreased ratio of floating
      rosette to total shoot weight. It is concluded that floating rosettes can enhance
      the inorganic carbon uptake of Callitriche. In contrast, air contact is of minor
      importance for nutrient transport.

PMID- 12228349
TI  - Role of Abscisic Acid in Drought-Induced Freezing Tolerance, Cold Acclimation,
      and Accumulation of LT178 and RAB18 Proteins in Arabidopsis thaliana.
AB  - To study the role of abscisic acid (ABA) in development of freezing tolerance of
      Arabidopsis thaliana, we exposed wild-type plants, the ABA-insensitive mutant
      abi1, and the ABA-deficient mutant aba-1 to low temperature (LT), exogenous ABA,
      and drought. Exposure of A. thaliana to drought stress resulted in a similar
      increase in freezing tolerance as achieved by ABA treatment or the initial stages
      of acclimation, suggesting overlapping responses to these environmental cues. ABA
      appears to be involved in both LT- and drought-induced freezing tolerance, since
      both ABA mutants were impaired in their responses to these stimuli. To correlate
      enhanced freezing tolerance with the presence of stress-specific proteins, we
      characterized the accumulation of RAB18 and LTI78 in two ecotypes, Landsberg
      erecta and Coimbra, and in the ABA mutants during stress response. LT- and
      drought-induced accumulation of RAB18 coincided with the increase in freezing
      tolerance and was blocked in the cold-acclimation-deficient ABA mutants. In
      contrast, LT178 accumulated in all genotypes in response to LT and drought and
      was always present when the plants were freezing tolerant. This suggests that
      development of freezing tolerance in A. thaliana requires ABA-controlled
      processes in addition to ABA-independent factors.

PMID- 12228351
TI  - Photoaffinity Labeling of Developing Jojoba Seed Microsomal Membranes with a
      Photoreactive Analog of Acyl-Coenzyme A (Acyl-CoA) (Identification of a Putative
      Acyl-CoA:Fatty Alcohol Acyltransferase.
AB  - Jojoba (Simmondsia chinensis, Link) is the only plant known that synthesizes
      liquid wax. The final step in liquid wax biosynthesis is catalyzed by an integral
      membrane enzyme, fatty acyl-coenzyme A (CoA):fatty alcohol acyltransferase, which
      transfers an acyl chain from acyl-CoA to a fatty alcohol to form the wax ester.
      To purify the acyltransferase, we have labeled the enzyme with a radioiodinated,
      photoreactive analog of acyl-CoA, 12-[N-(4-azidosalicyl)amino] dodecanoyl-CoA
      (ASD-CoA). This molecule acts as an inhibitor of acyltransferase activity in the
      dark and as an irreversible inhibitor upon exposure to ultraviolet light. Oleoyl
      CoA protects enzymatic activity in a concentration-dependent manner. Photolysis
      of microsomal membranes with labeled ASD-CoA resulted in strong labeling of two
      polypeptides of 57 and 52 kD. Increasing concentrations of oleoyl-CoA reduced the
      labeling of the 57-kD polypeptide dramatically, whereas the labeling of the 52-kD
      polypeptide was much less responsive to oleoyl-CoA. Also, unlike the other
      polypeptide, the labeling of the 57-kD polypeptide was enhanced considerably when
      photolyzed in the presence of dodecanol. These results suggest that a 57-kD
      polypeptide from jojoba microsomes may be the acyl-CoA:fatty alcohol
      acyltransferase.

PMID- 12228352
TI  - Individual Members of the Cab Gene Family Differ Widely in Fluence Response.
AB  - Chlorophyll a/b-binding protein genes (Cab genes) can be extremely sensitive to
      light. Transcript accumulation following a red light pulse increases with fluence
      over 8 orders of magnitude (L.S. Kaufman, W.F. Thompson, W.R. Briggs [1984]
      Science 226: 1447-1449). We have constructed fluence-response curves for
      individual Cab genes. At least two Cab genes (Cab-8 and AB96) show a very low
      fluence response to a single red light pulse. In contrast, two other Cab genes
      (AB80 and AB66) fail to produce detectable transcript following a single pulse of
      either red or blue light but are expressed in continuous red light. Thus, very
      low fluence responses and high irradiance responses occur in the same gene
      family.

PMID- 12228353
TI  - A Mutation in the D-de Loop of D1 Modifies the Stability of the S2QA- and S2QB-
      States in Photosystem II.
AB  - Photosystem II electron transfer, charge stabilization, and photoinhibition were
      studied in three site-specific mutants of the D1 polypeptide of Synechocystis PCC
      6803: E243K, E229D, and CA1 (deletion of three glutamates 242-244 and a
      substitution, glutamine-241 to histidine). The phenotypes of the E229D and E243K
      mutants were similar to that of the control strain (AR) in all of the studied
      aspects. The characteristics of CA1 were very different. Formate, which inhibits
      the QA- to QB- reaction, was severalfold less effective in CA1 than in AR. The
      S2QA- and S2QB- states were stabilized in CA1. It was previously shown that the
      electron transfer between QA- and QB was modified in CA1 (P Maenpaa, T. Kallio,
      P. Mulo, G. Salih, E.-M. Aro, E. Tyystjarvi, C. Jansson [1993] Plant Mol Biol 22:
      1-12). A change in the redox potential of the QA/QA- couple, which renders the
      reoxidation of QA- by back or forward reactions more difficult, could explain the
      phenotype of CA1. Although the rates of photoinhibition measured as inhibition of
      oxygen evolution, Chl fluorescence quenching, and decrease of thermoluminescence
      B and Q bands were similar in AR and CA1, the CA1 strain more quickly reached a
      state from which the cells were unable to recover their activity. The results
      described in this paper suggest that a modification in the structure of the D-de
      loop of D1 could influence the properties of the couple QA/QA- in D2 and the
      mechanism of recovery from photoinhibition.

PMID- 12228354
TI  - Electrical Impedance Analysis of Tissue Properties Associated with Ethylene
      Induction by Electric Currents in Cucumber (Cucumis sativus L.) Fruit.
AB  - A study based on electrical impedance analysis of tissue properties was conducted
      in order to understand the relationship between impedance components and ethylene
      biosynthesis induced by direct current in cucumber (Cucumis sativus L.) fruit.
      Impedances were measured at a range of alternating current frequencies from 500
      Hz to 1 MHz. We calculated capacitances representing the plasma membranes, C1,
      and organelle membranes, C2, and resistances representing extracellular space,
      R1, cytoplasm, R2, and organelle interior, R3. Direct current of 1 to 3 mA
      induced ethylene synthesis with a sharp peak at 1 h. The rate of production was
      greater with a stronger current. This abrupt induction of ethylene synthesis was
      accompanied by an equally abrupt activation of 1-aminocyclopropane-1-carboxylic
      acid (ACC) synthase within 1 h, but not that of ACC oxidase, which was activated
      only at the later stages of the treatment at a time when ethylene production and
      ACC synthase activity were declining. Using direct current of 0 to 3 mA, C2, R1,
      and R2 increased abruptly, and C1 increased gradually after 3 h. The rates of
      increases were greater with currents of larger magnitude, R3 was not affected
      during passage of the current. Diazocyclopentadiene, an inhibitor of ethylene
      action, eliminated the direct current induction of R1 but had no effect on the
      increases in C2 and R2. Diazocyclopentadiene counteracted the stimulative effects
      of exogenously applied ethylene with respect to respiration and activities of ACC
      oxidase and phenylalanine ammonia-lyase. These results indicate that an
      externally applied current may generate signal(s) by altering the functions of
      organelle membranes and/or cytoplasmic pH to induce ACC synthase.

PMID- 12228355
TI  - Characterization of a Phosphate-Accumulator Mutant of Arabidopsis thaliana.
AB  - We have characterized a novel mutation of Arabidopsis thaliana at a locus
      designated pho2. pho2 mutants accumulated up to 3-fold more total P in leaves,
      mostly as inorganic phosphate (Pi), than wild-type seedlings. In addition, we
      isolated a mutant (locus designated pho1-2, an allelle of pho1-1 described by Y.
      Poirier, S. Thoma, C. Somerville, J. Schiefelbein [1991] Plant Physiol 97: 1087
      1093) with low Pi concentrations in leaves. When grown under high transpiration
      conditions, leaves of pho2 seedlings became severely P intoxicated, whereas
      shoots of pho1-2 mutants were P deficient and wild-type seedlings were normal. A
      pho1/pho2 double mutant resulting from a cross between the single mutants was
      identified in the F2 generation and shown to have a pho1 phenotype. Prior to the
      development of P toxicity symptoms, P was the only mineral nutrient whose
      concentration was greater in pho2 mutants than wild-type seedlings. Compared to
      wild-type, pho2 mutants had greater Pi concentrations in stems, siliques, and
      seeds, but roots of pho2 mutants had similar or lower Pi concentrations than
      either pho1 mutants or wild-type seedlings. We suggest that the pho2 mutation
      affects a function normally involved in regulating the concentration of Pi in
      shoots of Arabidopsis.

PMID- 12228356
TI  - Regulation of Photosynthesis during Leaf Development in RbcS Antisense DNA
      Mutants of Tobacco.
AB  - We have previously characterized RbcS antisense DNA mutants of tobacco that have
      drastic reductions in their content of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco; S.R. Rodermel, M.S. Abbott, L. Bogorad [1988]
      Cell 55: 673-681). In this report we examine the impact of Rubisco loss on
      photosynthesis during tobacco (Nicotiana tabacum) leaf development.
      Photosynthetic capacities are depressed in the antisense leaves, but the patterns
      of change in photosynthetic rates during the development of these leaves are
      similar to those in wild-type plants: after attaining a maximum in young leaves,
      photosynthetic capacities undergo a prolonged senescence decline in older leaves.
      The alterations in photosynthetic capacities in both the wild type and mutant are
      closely correlated with changes in Rubisco activity and content. During wild-type
      leaf development, Rubisco accumulation is regulated by coordinate changes in RbcS
      and rbcL transcript accumulation, whereas in the antisense leaves, Rubisco
      content is a function of RbcS, but not rbcL, transcript abundance. This indicates
      that large subunit protein production is controlled posttranscriptionally in the
      mutants. The antisense leaves accumulate near-normal levels of chlorophyll and
      representative photosynthetic proteins throughout development, suggesting that
      photosynthetic gene expression is not feedback regulated by Rubisco abundance.
      Considered together, the data in this paper indicate that leaf developmental
      programs are generally insensitive to sharp reductions in Rubisco content and
      emphasize the metabolic plasticity of plant cells in achieving optimal
      photosynthetic rates.

PMID- 12228357
TI  - STUNTED PLANT 1, A Gene Required for Expansion in Rapidly Elongating but Not in
      Dividing Cells and Mediating Root Growth Responses to Applied Cytokinin.
AB  - To understand the control of spatial patterns of expansion, we have studied root
      growth in wild type and in the stunted plant 1 mutant, stp1, of Arabidopsis
      thaliana. We measured profiles of cell length and calculated the distribution of
      elongation rate. Slow growth of stp1 results both from a failure of dividing cell
      number to increase and from low elongation rates in the zone of rapid expansion.
      However, elongation of dividing cells was not greatly affected, and stp1 and wild
      type callus grew at identical rates. Thus, rapid cellular expansion differs in
      mechanism from expansion in dividing cells and is facilitated by the STP1 gene.
      Additionally, there was no difference between stp1 and wild-type roots for
      elongation in response to abscisic acid, auxin, ethylene, or gibberellic acid or
      for radial expansion in response to ethylene; however, stp1 responded to
      cytokinin much less than wild type. In contrast, both genotypes responded
      comparably to hormones when explants were cultured; in particular, there was no
      difference between genotypes in shoot regeneration in response to cytokinin.
      Thus, effects on root expansion mediated by cytokinin, but not effects mediated
      by other hormones or effects on other cytokinin-mediated responses, require the
      STP1 locus.

PMID- 12228358
TI  - Quantification of the Contribution of CO2, HCO3-, and External Carbonic Anhydrase
      to Photosynthesis at Low Dissolved Inorganic Carbon in Chlorella saccharophila.
AB  - An equation has been developed incorporating whole-cell rate constants for CO2
      and HCO3- that describes accurately photosynthesis (Phs) in suspensions of
      unicellular algae at low dissolved inorganic carbon. At pH 8.0 the concentration
      of CO2 available to the algal cells depends on the rate of supply from, and the
      loss to, HCO3- and the rate of use by the cells. At elevated cell densities (>30
      mg chlorophyll [Chl] L-1), at which CO2 use by the cells is high, the slope of a
      graph of absolute Phs versus Chl concentration approaches the rate of Phs on a
      milligram of Chl basis because of HCO3- use alone. The slope of a graph of Phs
      versus HCO3- will be the rate constant for HCO3-, and for Chlorella saccharophila
      it was 0.16 L mg-1 Chl h-1. The difference between the constants for dissolved
      inorganic carbon (measured in cells with external carbonic anhydrase) and HCO3-1
      is the constant for CO2, which was 26 L mg-1 Chl h-1. This difference causes the
      half-saturation constant for Phs to increase 5- to 6-fold at high cell densities.
      The increase in CO2 use as a result of external carbonic anhydrase is described
      mathematically as a function of cell density.

PMID- 12228359
TI  - The Impact of Chlorophyll-Retention Mutations, d1d2 and cyt-G1, during Embryogeny
      in Soybean.
AB  - The ultrastructural, physiological, and molecular changes in developing and
      mature seeds were monitored in a control line (Glycine max [L.] Merr., cv Clark)
      that exhibited seed degreening and two mutant lines (d1d2 and cyt-G1) that
      retained chlorophyll upon seed maturation. Ultrastructural studies showed that
      the control line had no internal membranes, whereas stacked thylakoid membranes
      were detected in the green seed from the mutant lines. Pigment analyses indicated
      that total chlorophyll was lowest in the mature seeds of the control line. Mature
      d1d2 and cyt-G1 seed had elevated Chl a and Chl b levels, respectively. In both
      control and mutant lines, Lhcb1, Lhcb2, and RbcS mRNAs were abundant in embryos
      prior to cotyledon filling, declined after the onset of storage protein
      accumulation, and were barely detectable or undetectable in all later stages of
      seed development. Therefore, the chlorophyll-retention phenotype must be a result
      of the alteration of a process that occurs after translation of photosynthesis
      related mRNAs to stabilize apoprotein and pigment levels. Furthermore, different
      elements controlling either the synthesis or turnover of Chl a and Chl b must be
      impaired in the d1d2 and cyt-G1 lines. No reproducible differences in total leaf,
      embryonic, and chloroplast protein profiles and plastid DNAs could be correlated
      with the mutations that induced chlorophyll retention.

PMID- 12228360
TI  - Aluminum Toxicity and Tolerance in Plants.

PMID- 12228361
TI  - Rethinking Auxin Biosynthesis and Metabolism.

PMID- 12228362
TI  - Aluminum-Induced Genes (Induction by Toxic Metals, Low Calcium, and Wounding and
      Pattern of Expression in Root Tips).
AB  - We have investigated the response of four Al-induced genes (wali1, -3, -4, and 
      5) from wheat (Triticum aestivum L.) to other stresses. The relative transcript
      levels of wali1 (encoding a plant metallothionein-like protein), wali3 and wali5
      (putative Bowman-Birk proteinase inhibitors), and wali4 (phenylalanine
      ammonialyase) increased in root tips of wheat after 2-d treatments with toxic
      levels of all other metals tested (Cd, Fe, Zn, Cu, Ga, In, and La). The
      expression levels of wali1, -3, -4, and -5 also increased in the root tips of
      plants grown in the presence of low levels of Ca (10[mu]M). The transcript levels
      of wali1, -3, and -5 increased in wounded leaf and root tissue, whereas the
      transcript levels of wali4 increased only in wounded leaves. The site of
      expression of wali1, -3, and -5 in root tips was identified using in situ
      hybridization. wali1 was expressed predominantly in the meristematic tissue of
      the root tip, whereas wali3 and wali5 were expressed predominantly in the
      cortical tissue of the root. Some changes in the site of expression of these
      genes were evident in the roots of Al-treated plants.

PMID- 12228363
TI  - The Refined Three-Dimensional Structure of Pectate Lyase C from Erwinia
      chrysanthemi at 2.2 Angstrom Resolution (Implications for an Enzymatic
      Mechanism).
AB  - The crystal structure of pectate lyase C (EC 4.2.2.2) from the enterobacterium
      Erwinia chrysanthemi (PelC) has been refined by molecular dynamics techniques to
      a resolution of 2.2 A to an R factor of 17.97%. The final model consists of 352
      of the total 353 amino acids and 114 solvent molecules. The root-mean-square
      deviation from ideality is 0.009 A for bond lengths and 1.768[deg] for bond
      angles. The structure of PelC bound to the lanthanide ion lutetium, used as a
      calcium analog, has also been refined. Lutetium inhibits the enzymatic activity
      of the protein, and in the PelC-lutetium structure, the ion binds in the putative
      calcium-binding site. Five side-chain atoms form ligands to the lutetium ion. An
      analysis of the atomic-level model of the two protein structures reveals possible
      implications for the enzymatic mechanism of the enzyme.

PMID- 12228364
TI  - Export of Abscisic Acid, 1-Aminocyclopropane-1-Carboxylic Acid, Phosphate, and
      Nitrate from Roots to Shoots of Flooded Tomato Plants (Accounting for Effects of
      Xylem Sap Flow Rate on Concentration and Delivery).
AB  - We determined whether root stress alters the output of physiologically active
      messages passing from roots to shoots in the transpiration stream. Concentrations
      were not good measures of output. This was because changes in volume flow of
      xylem sap caused either by sampling procedures or by effects of root stress on
      rates of whole-plant transpiration modified concentrations simply by dilution.
      Thus, delivery rate (concentration x sap flow rate) was preferred to
      concentration as a measure of solute output from roots. To demonstrate these
      points, 1-aminocyclopropane-1-carboxylic acid (ACC), abscisic acid, phosphate,
      nitrate, and pH were measured in xylem sap of flooded and well-drained tomato
      (Lycopersicon esculentum Mill., cv Ailsa Craig) plants expressed at various rates
      from pressurized detopped roots. Concentrations decreased as sap flow rates were
      increased. However, dilution of solutes was often less than proportional to flow,
      especially in flooded plants. Thus, sap flowing through detopped roots at whole
      plant transpiration rates was used to estimate solute delivery rates in intact
      plants. On this basis, delivery of ACC from roots to shoots was 3.1-fold greater
      in plants flooded for 24 h than in well-drained plants, and delivery of phosphate
      was 2.3-fold greater. Delivery rates of abscisic acid and nitrate in flooded
      plants were only 11 and 7%, respectively, of those in well-drained plants.

PMID- 12228365
TI  - Low Water Potential Disrupts Carbohydrate Metabolism in Maize (Zea mays L.)
      Ovaries.
AB  - Water deficit during pollination increases the frequency of kernel abortion in
      maize (Zea mays L.). Much of the kernel loss is attributable to lack of current
      photosynthate, but a large number of kernels fail to develop on water-deficient
      plants even when assimilate supply is increased. We examined the possibility that
      assimilate utilization by developing ovaries might be impaired at low water
      potential ([Psi]w). Plants were grown in the greenhouse in 20-L pots containing
      22 kg of amended soil. Water was withheld on the first day silks emerged, and
      plants were hand-pollinated 4 d later when leaf [Psi]w decreased to approximately
      - 1.8 MPa and silk [Psi]w was approximately -1.0 MPa. Plants were rehydrated 2 d
      after pollination. The brief water deficit inhibited ovary growth (dry matter
      accumulation) and decreased kernel number per ear by 60%, compared to controls.
      Inhibition of ovary growth was associated with a decrease in the level of
      reducing sugars, depletion of starch, a 75-fold increase in sucrose concentration
      (dry weight basis), and inhibition of acid invertase (EC 3.2.1.26) activity.
      These results indicate that water deficits during pollination disrupt
      carbohydrate metabolism in maize ovaries. They suggest that acid invertase
      activity is important for establishing and maintaining reproductive sink strength
      during pollination and early kernel development.

PMID- 12228366
TI  - Light-Induced Chloroplast [alpha]-Amylase in Pearl Millet (Pennisetum
      americanum).
AB  - In pearl millet (Pennisetum americanum) seedlings light induces the appearance of
      a leaf [alpha]-amylase isozyme. The leaf [alpha]-amylase isozyme was present in
      enriched amounts in isolated chloroplast but it could not be detected in isolated
      etioplasts. The chloroplast [alpha]-amylase was present in both mesophyll and
      bundle-sheath chloroplasts. Preliminary characterization indicated that molecular
      properties of chloroplast [alpha]-amylase were like those of a typical [alpha]
      amylase. The plastidic [alpha]-amylase had a molecular mass of 46 kD, pH optimum
      of 6.2, required Ca2+ for activity and thermostability, but lost activity in the
      presence of ethylenediaminetetracetate. Plastidic [alpha]-amylase activity after
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis could be renatured in
      situ by Triton X-100. Western blot analysis demonstrated that this protein was
      antigenically similar to a maize seed [alpha]-amylase. In vivo [35S]methionine
      labeling of bundle-sheath strands isolated from light-grown leaves followed by
      immunoprecipitation revealed that bundlesheath strands synthesized plastidic
      [alpha]-amylase de novo.

PMID- 12228367
TI  - The Utilization of Glycolytic Intermediates as Precursors for Fatty Acid
      Biosynthesis by Pea Root Plastids.
AB  - Radiolabeled pyruvate, glucose, glucose-6-phosphate, acetate, and malate are all
      variously utilized for fatty acid and glycerolipid biosynthesis by isolated pea
      (Pisum sativum L.) root plastids. At the highest concentrations tested (3-5mM),
      the rates of incorporation of these precursors into fatty acids were 183, 154,
      125, 99 and 57 nmol h-1 mg-1 protein, respectively. In all cases, cold pyruvate
      consistently caused the greatest reduction, whereas cold acetate consistently
      caused the least reduction, in the amounts of each of the other radioactive
      precursors utilized for fatty acid biosynthesis. Acetate incorporation into fatty
      acids was approximately 55% dependent on exogenously supplied reduced nucleotides
      (NADH and NADPH), whereas the utilization of the remaining precursors was only
      approximately 10 and 20% dependent on added NAD(P)H. In contrast, the utilization
      of all precursors was greatly dependent (85-95%) on exogenously supplied ATP.
      Palmitate, stearate, and oleate were the only fatty acids synthesized from
      radioactive precursors. Higher concentrations of each precursor caused increased
      proportions of oleate and decreased proportions of palmitate synthesized.
      Radioactive fatty acids from all precursors were incorporated into glycerolipids.
      The data presented indicate that the entire pathway from glucose, including
      glycolysis, to fatty acids and glycerolipids is operating in pea root plastids.
      This pathway can supply both carbon and reduced nucleotides required for fatty
      acid biosynthesis but only a small portion of the ATP required

PMID- 12228368
TI  - Dark Leaf Respiration in Light and Darkness of an Evergreen and a Deciduous Plant
      Species.
AB  - Dark respiration in light as well as in dark was estimated for attached leaves of
      an evergreen (Heteromeles arbutifolia Ait.) and a deciduous (Lepechinia fragans
      Greene) shrub species using an open gas-exchange system. Dark respiration in
      light was estimated by the Laisk method. Respiration rates in the dark were
      always higher than in the light, indicating that light inhibited respiration in
      both species. The rates of respiration in the dark were higher in the leaves of
      the deciduous species than in the evergreen species. However, there were no
      significant differences in respiration rates in light between the species. Thus,
      the degree of inhibition of respiration by light was greater in the deciduous
      species (62%) than in the evergreen species (51%). Respiration in both the light
      and darkness decreased with increasing leaf age. However, because respiration in
      the light decreased faster with leaf age than respiration in darkness, the degree
      of inhibition of respiration by light increased with leaf age (from 36% in the
      youngest leaves to 81% in the mature leaves). This suggests that the rate of dark
      respiration in the light is related to the rate of biosynthetic processes. Dark
      respiration in the light decreased with increasing light intensity. Respiration
      both in the light and in the dark was dependent on leaf temperature. We concluded
      that respiration in light and respiration in darkness are tightly coupled, with
      variation in respiration in darkness accounting for more than 60% of the
      variation in respiration in light. Care must be taken when the relation between
      respiration in light and respiration in darkness is studied, because the relation
      varies with species, leaf age, and light intensity.

PMID- 12228369
TI  - Interspecific Gene Transfer (Implications for Broadening Temperature
      Characteristics of Plant Metabolic Processes).
AB  - We report here an approach to metabolic engineering to alter the temperature
      characteristics of an enzyme pool based on the concept of thermal kinetics
      windows (TKWs), a useful indicator of enzyme performance. A chimeric cucumber
      NADH-hydroxypyruvate reductase (HPR) gene under the control of a cauliflower
      mosaic virus 35S promoter was constructed and introduced into the genome of
      tobacco (Tobacum tobacum). The root system of the R1 generation of the resultant
      transgenic plants expresses only the cucumber enzyme (the native tobacco HPR gene
      is light regulated and only found in the aerial portions of the plant). Enzyme
      isolated from the transgenic root tissues exhibits a TKW centered at 32.5[deg]C,
      characteristic of cucumber. The pool of HPR in the shoots, containing both
      tobacco and cucumber enzymes, exhibits a broad TKW consistent with an equal mix
      of the two forms. These data do not simply demonstrate that an introduced gene
      can be expressed in a transgenic plant but that the kinetics properties of the
      resultant enzyme are unaltered and when sufficient enzyme is produced the
      temperature characteristics of the total pool are altered. This suggests that the
      temperature characteristics of plant biochemical pathways can be broadened to
      suit changing thermal environments.

PMID- 12228370
TI  - Purification, Characterization, and Submitochondrial Localization of a 58
      Kilodalton NAD(P)H Dehydrogenase.
AB  - An NADH dehydrogenase activity from red beet (Beta vulgaris L.) root mitochondria
      was purified to a 58-kD protein doublet. An immunologically related dehydrogenase
      was partially purified from maize (Zea mays L. B73) mitochondria to a 58-kD
      protein doublet, a 45-kD protein, and a few other less prevalent proteins.
      Polyclonal antibodies prepared against the 58-kD protein of red beet roots were
      found to immunoprecipitate the NAD(P)H dehydrogenase activity. The antibodies
      cross-reacted to similar proteins in mitochondria from a number of plant species
      but not to rat liver mitochondrial proteins. The polyclonal antibodies were used
      in conjunction with maize mitochondrial fractionation to show that the 58-kD
      protein was likely part of a protein complex loosely associated with the membrane
      fraction. A membrane-impermeable protein cross-linking agent was used to further
      show that the majority of the 58-kD protein was located on the outer surface of
      the inner mitochondrial membrane or in the intermembrane space. Analysis of the
      cross-linked 58-kD NAD(P)H dehydrogenase indicated that specific proteins of 64,
      48, and 45 kD were cross-linked to the 58-kD protein doublet. The NAD(P)H
      dehydrogenase activity was not affected by ethyleneglycol-bis([beta]-aminoethyl
      ether)-N,N[prime] -tetraacetic acid or CaCl2, was stimulated somewhat (21%) by
      flavin mononucleotide, was inhibited by p-chloromercuribenzoic acid (49%) and
      mersalyl (40%), and was inhibited by a bud scale extract of Platanus occidentalis
      L. containing platanetin (61%).

PMID- 12228371
TI  - Identification of a Protein That Inhibits the Phosphorylated Form of Nitrate
      Reductase from Spinach (Spinacia oleracea) Leaves.
AB  - The low-activity, phosphorylated form of nitrate reductase (NR) became activated
      during purification from spinach (Spinacia oleracea) leaves harvested in the
      dark. This activation resulted from its separation from an approximately 110-kd
      nitrate reductase inhibitor protein (NIP). Readdition of NIP inactivated the
      purified phosphorylated NR, but not the active dephosphorylated form of NR,
      indicating that the inactivation of NR requires its interaction with NIP as well
      as phosphorylation. Consistent with this hypothesis, NR that had been inactivated
      in vitro in the presence of NR kinase, ATP-Mg, and NIP could be reactivated
      either by dephosphorylation with protein phosphatase 2A or by dissociation of NIP
      from NR.

PMID- 12228372
TI  - Characteristics of Sucrose Transport and Sucrose-Induced H+ Transport on the
      Tonoplast of Red Beet (Beta vulgaris L.) Storage Tissue.
AB  - Sucrose-induced changes of the energization state of the red beet root (Beta
      vulgaris L. ssp. conditiva) vacuolar membrane were observed with the fluorescent
      dyes 6-chloro-9-{[4-(diethylamino)- 1-methylbutyl]-amino}-2-methoxyacridine
      dihydrochloride, as a pH monitor, and 9-amino-6-chloro-2-methoxyacridine (ACMA).
      Consequently, transient acidification of the surrounding suspension medium could
      be measured with a pH electrode. This signal was specific for Suc and was not
      seen for sorbitol, mannitol, or maltose. Sucrose-induced medium acidification was
      sensitive to the same inhibitors that were efficient in inhibiting sucrose
      transport, including the monoclonal antibodies TNP56-12 and C50-5-3. It was seen
      with vacuoles and vesicles energized with MgATP before sucrose was added but also
      with vacuoles not artificially energized previously. Using bafilomycin A1 for the
      inhibition of the vacuolar ATPase of vacuoles previously energized by MgATP,
      apparent Km values for H+ export from the vacuoles to the medium could be
      calculated taking into account the passive proton leak. Apparent Km values for H+
      export determined from data obtained with pH measurements in the medium and with
      ACMA corresponded to those obtained previously for sucrose uptake. Comparing
      sucrose uptake rates with corresponding H+ export rates at the respective sucrose
      concentrations and at Km, a stoichiometry of approximately one proton per
      transported sucrose was estimated.

PMID- 12228373
TI  - Repression of Acetolactate Synthase Activity through Antisense Inhibition
      (Molecular and Biochemical Analysis of Transgenic Potato (Solanum tuberosum L. cv
      Desiree) Plants).
AB  - Acetolactate synthase (ALS), the first enzyme in the biosynthetic pathway of
      leucine, valine, and isoleucine, is the biochemical target of different
      herbicides. To investigate the effects of repression of ALS activity through
      antisense gene expression we cloned an ALS gene from potato (Solanum tuberosum L.
      cv Desiree), constructed a chimeric antisense gene under control of the
      cauliflower mosaic virus 35S promoter, and created transgenic potato plants
      through Agrobacterium tumefaciens-mediated gene transfer. Two regenerants
      revealed severe growth retardation and strong phenotypical effects resembling
      those caused by ALS-inhibiting herbicides. Antisense gene expression decreased
      the steady-state level of ALS mRNA in these plants and induced a corresponding
      decrease in ALS activity of up to 85%. This reduction was sufficient to generate
      plants almost inviable without amino acid supplementation. In both ALS antisense
      and herbicide-treated plants, we could exclude accumulation of 2-oxobutyrate
      and/or 2-aminobutyrate as the reason for the observed deleterious effects, but we
      detected elevated levels of free amino acids and imbalances in their relative
      proportions. Thus, antisense inhibition of ALS generated an in vivo model of
      herbicide action. Furthermore, expression of antisense RNA to the enzyme of
      interest provides a general method for validation of potential herbicide targets.

PMID- 12228374
TI  - Isolation, Purification, and Characterization of Mitochondria from Chlamydomonas
      reinhardtii.
AB  - Mitochondria were isolated from autotrophically grown Chlamydomonas reinhardtii
      cell-wall-less mutant CW 92. The cells were broken by vortexing with glass beads,
      and the mitochondria were collected by differential centrifugation and purified
      on a Percoll gradient. The isolated mitochondria oxidized malate, pyruvate,
      succinate, NADH, and [alpha]-ketoglutarate. Respiratory control was obtained with
      malate (2.0) and pyruvate (2.2) but not with the other substrates. From
      experiments with KCN and salicylhydroxamic acid, it was estimated that the
      capacity of the cytochrome pathway was at least 100 nmol O2 mg-1 protein min-1
      and the capacity of the alternative oxidase was at least 50 nmol O2 mg-1 protein
      min-1. A low sensitivity to oligomycin indicates some difference in the
      properties of the mitochondrial ATPase from Chlamydomonas as compared to higher
      plants.

PMID- 12228375
TI  - Perception of Fungal Sterols in Plants (Subnanomolar Concentrations of Ergosterol
      Elicit Extracellular Alkalinization in Tomato Cells).
AB  - Suspension-cultured cells of tomato (Lycopersicon esculentum Mill.) reacted to
      spores and spore exudates of the pathogen Cladosporium fulvum with a rapid,
      transient alkalinization of their growth medium that resembled the previously
      described alkalinization response elicited by chitin fragments (G. Felix, M.
      Regenass, T. Boller [1993] Plant J 4: 307-316) and was likewise inhibited by the
      protein kinase inhibitor K-252a. However, the spore factor recognized by the
      cells differed from chitin fragments in that it was butanol soluble and active in
      cells refractory to stimulation by chitin fragments. The spore factor was
      purified and identified as ergosterol, the main sterol of most higher fungi. With
      pure ergosterol, half-maximal induction was reached at about 10 pm. After
      treatment with ergosterol, tomato cells became refractory to a subsequent
      stimulation by C. fulvum and vice versa, indicating that ergosterol was the
      principal component of the spores recognized by the plant cells. Most other
      sterols were inactive, including cholesterol, a range of animal steroid hormones,
      and all natural plant sterols tested, except for stigmasterol, which was about
      106 times less active than ergosterol. Our data demonstrate that tomato cells
      perceive ergosterol with a selectivity and sensitivity that resembles the
      perception of steroid hormones in animals.

PMID- 12228376
TI  - Purification and Characterization of a Soluble Phosphatidylinositol 4-Kinase from
      Carrot Suspension Culture Cells.
AB  - Previously we reported the presence of a soluble phosphatidylinositol 4-kinase
      (PI 4-Kinase) in carrot (Daucus carota L.) suspension culture cells (C.M. Okpodu,
      W. Gross, W.F. Boss [1990] Plant Physiol 93: S-63). We have purified the enzyme
      over 1000-fold using Q-Sepharose ion exchange, hydroxylapatite, and G-100 gel
      filtration column chromatography. The Mr of the enzyme was estimated to be 83,000
      by gel filtration. PI 4-kinase activity was recovered after renaturation of the
      80-kD region of polyacrylamide gels, and an 80-kD peptide cross-reacted with
      antibodies to the yeast 55-kD membrane-associated PI 4-kinase on western blots.
      The isolated lipid kinase phosphorylated PI but not lysophosphatidylinositol or
      phosphatidylinositol monophosphate. Maximal PI kinase activity occurred when the
      substrate was added as Triton X-100/PI mixed micelles at pH 8. The enzyme
      required divalent cations. At low concentrations (1-5 mM), Mn2+ was more
      effective than Mg2+ in increasing enzyme activity; however, maximal activity
      occurred at 25 to 40 mM Mg2+. Calcium from 0.01 [mu]M to 1 mM had no effect on
      the enzyme activity. The Km of the enzyme for ATP was estimated to be between 400
      and 463 [mu]M. The enzyme was inhibited by adenosine (100 [mu]M); however, ADP
      (up to 100 [mu]M) had no effect on the activity. The biochemical characteristics
      of the carrot soluble PI 4-kinase are compared with the previously reported PI 4
      kinases from animals and yeast.

PMID- 12228377
TI  - Localization of Hydrogen Peroxide Production in Pisum sativum L. Using Epi
      Polarization Microscopy to Follow Cerium Perhydroxide Deposition.
AB  - Cerium is becoming an increasingly popular reagent for histochemical localization
      of oxidases and phosphatases because it combines directly with reaction products
      to form fine precipitates of electron-dense materials that can be easily detected
      using transmission electron microscopy or laser confocal scanning microscopy. We
      used epi-polarization microscopy to detect cerium perhydroxide deposits formed
      when H2O2 was produced by diamine oxidase in pea (Pisum sativum L.) epicotyls
      exposed to exogenous putrescine. Diamine oxidase activity was abundant in
      cortical cell walls but showed little, if any, association with vascular tissues.
      Maps of cerium deposition generated using scanning electron microscopy/x-ray
      microanalysis verified these observations. This study demonstrates the use of epi
      polarization microscopy to follow cerium deposition, and the ready accessibility
      of this microscopy technique should facilitate more widespread use of cerium for
      plant histochemistry and cytochemistry.

PMID- 12228378
TI  - Photosynthetic Carbon Metabolism and Translocation in Wild-Type and Starch
      Deficient Mutant Nicotiana sylvestris L.
AB  - A high rate of daytime export of assimilated carbon from leaves of a starch
      deficient mutant tobacco (Nicotiana sylvestris L.) was found to be a key factor
      that enabled shoots to grow at rates comparable to those in wild-type plants
      under a 14-h light period. Much of the newly fixed carbon that would be used for
      starch synthesis in leaves of wild-type plants was used instead for sucrose
      synthesis in the mutant. As a result, export doubled and accumulation of sucrose
      and hexoses increased markedly during the day in leaves of the mutant plants. The
      increased rate of export to sink leaves appeared to be responsible for the
      increase in the proportion of their growth that occurred during the day compared
      to wild-type plants. Daytime growth of source leaves also increased, presumably
      as a result of the increased accumulation of recently assimilated soluble carbon
      in the leaves. Even though starch accumulation did not occur in the leaves of
      mutant plants, nearly all the sugar that accumulated during the day was exported
      in the period of decreasing irradiance at the end of the diurnal light period.
      Changes in carbon allocation that occurred in leaves of wild-type and mutant
      plants near the end of the light period appeared to result from endogenous
      diurnal regulation associated with the day-night transition.

PMID- 12228379
TI  - Synthesis of Phytochelatins and Homo-Phytochelatins in Pisum sativum L.
AB  - In the roots of pea plants (Pisum sativum L.) cultivated with 20 [mu]M CdCl2 for
      3 d, synthesis of phytochelatins [PCs or ([gamma]EC)nG, where [gamma]EC is
      [gamma]glutamylcysteine and G is glycine] and homophytochelatins [h-PCs,
      ([gamma]EC)n[beta]-alanine] is accompanied by a drastic decrease in glutathione
      (GSH) content, but an increase in homoglutathione (h-GSH) content. In contrast,
      the in vitro activity of GSH synthetase increases 5-fold, whereas h-GSH
      synthetase activity increases regardless of Cd exposure. The consititutive enzyme
      PC synthase, which catalyzes the transfer of the [gamma]-EC moiety of GSH to an
      acceptor GSH molecule thus producing ([gamma]EC)2G, is activated by heavy metals,
      with Cd and Cu being strong activators and Zn being a very poor activator. Using
      h-GSH or hm-GSH for substrate, the synthesis rate of([gamma]EC)2[beta]-alanine
      and [gamma]EC)2-serine is only 2.4 and 0.3%, respectively, of the sythesis rate
      of ([gamma]EC)2G with GSH as substrate. However, in the presence of a constant
      GSH level, increasing the concentration of h-GSH or hm-GSH results in increased
      synthesis of ([gamma]EC)2[beta]-alanine or ([gamma]EC)2-serine, respecively;
      simultaneously, the synthesis of ([gamma]EC)2G is inhibited. [gamma]EC is not a
      substrate of PC synthase. These results are best explained by assuming that PC
      synthase has a [gamma]EC donor binding site, which is very specific for GSH, and
      a [gamma]EC acceptor binding site, which is less specific and accepts several
      tripeptides, namely GSH, h-GSH, and hm-GSH.

PMID- 12228380
TI  - Phytochrome-Mediated Light Regulation of PHYA- and PHYB-GUS Transgenes in
      Arabidopsis thaliana Seedlings.
AB  - Phytochrome wild-type gene-[beta]-glucuronidase (PHY-GUS) gene fusions were used
      in transgenic Arabidopsis to compare the activity levels and light regulation of
      the PHYA and PHYB promoters and to identify the photoreceptors mediating this
      regulation. In dark-grown seedlings, both promoters are 4-fold more active in
      shoots than in roots,but the PHYA promoter is nearly 20-fold more active than
      that of PHYB in both organs. In shoots, white light represses the activities of
      the PHYA and PHYB promoters 10- and 2-fold, respectively, whereas in roots light
      has no effect on the PHYA promoter but increases PHYB promoter activity 2-fold.
      Consequently, PHYA promoter activity remains higher than that of PHYB in light in
      both shoots (5-fold) and roots (11-fold). Experiments with narrow-waveband light
      and photomorphogenic mutants suggest that no single photoreceptor is necessary
      for full white-light-directed PHYA repression in shoots, but that multiple,
      independent photoreceptor pathways are sufficient alone or in combination. In
      contrast, phytochrome B appears both necessary and sufficient for a light
      mediated decrease in PHYB activity in shoots, and phytochrome A mediates a far
      red-light-stimulated increase in PHYB promoter activity. Together, the data
      indicate that the PHYA and PHYB genes are regulated in divergent fashion at the
      transcriptional level, both developmentally and by the spectral distribution of
      the prevailing light, and that this regulation may be important to the
      photosensory function of the two photoreceptors.

PMID- 12228381
TI  - The Lipoxygenase Isozymes in Soybean [Glycine max (L.) Merr.] Leaves (Changes
      during Leaf Development, after Wounding, and following Reproductive Sink
      Removal).
AB  - The levels of individual lipoxygenase isozymes in soybean [Glycine max (L.)
      Merr.] leaves were assessed during leaf development, after mechanical wounding,
      and in response to reproductive sink removal. Native isoelectric focusing
      followed by immunoblotting was employed to examine individual lipoxygenase
      isozymes. In leaves of all ages, two distinct classes of lipoxygenase isozymes
      were detected. One class of lipoxygenase isozymes had nearly neutral isoelectric
      points (pls) ranging from pH 6.8 to 7.2. The other class of lipoxygenase isozymes
      had acidic pls ranging from pH 4.7 to 5.6. During leaf development, all of the
      neutral lipoxygenase isozymes and most of the acidic isozymes were present in
      greatest abundance in the youngest leaves examined and declined in amount as leaf
      age increased. However, four acidic lipoxygenase isozymes (pl = 4.70, 4.80, 4.90,
      4.95) were more abundant in intermediateage leaves than in either the youngest or
      oldest leaves examined. Following mechanical wounding of leaves, these same four
      acidic isozymes also increased in abundance both locally and systemically in
      leaves from wounded plants. Unlike the specific effects of wounding on the
      lipoxygenase isozymes in leaves, reproductive sink removal stimulated a general
      increase in most of the acidic lipoxygenase isozymes in leaves.

PMID- 12228382
TI  - Partial Purification and Characterization of Hydroxycinnamoyl-Coenzyme A:Tyramine
      Hydroxycinnamoyltransferase from Cell Suspension Cultures of Solanum tuberosum.
AB  - A pathogen elicitor-inducible soluble acyltransferase (tyramine
      hydroxycinnamoyltransferase [THT], EC 2.3.1), which catalyzes the transfer of
      hydroxycinnamic acids from hydroxycinnamoyl-coenzyme A (CoA) esters to tyramine
      in the formation of N-hydroxycinnamoyltyramine, was partially purified with a 380
      fold enrichment and a 6% recovery from cell-suspension cultures of potato
      (Solanum tuberosum L. cv Datura). The enzyme showed specific activities of 33
      mkat (kg protein)-1 (formation of feruloyltyramine). The apparent native Mr was
      found to be approximately 49,000. Highest activity was at pH 6.8 in K-phosphate.
      The isoelectric point of the enzyme was approximately pH5.2. The apparent energy
      of activation was calculated to be 96 kJ mol-1. The enzyme activity was
      stimulated more than 5-fold by 10 mM Ca2+ or Mg2+. The apparent Km values were 36
      [mu]M for feruloyl-CoA and 85 and 140 [mu]M for cinnamoyl- and 4-coumaroyl-CoA,
      respectively. The Km value for tyramine in the presence of feruloyl-CoA was 22
      [mu]M. In the presence of 4-coumaroyl-CoA, however, the Km for tyramine increased
      to about 230 [mu]M. The mode of action was an iso-ordered bi bi mechanism in
      which A, B, P, and Q equal hydroxycinnamoyl-CoA, tyramine, N
      hydroxycinnamoyltyramine, and CoA, respectively. Thus, the reaction occurred in a
      ternary complex of the enzyme and substrates. The equilibrium constant of the
      reaction was determined to be 1.3 x 104. This gave a [delta]G[deg][prime] eq
      value of -23.5 kJ mol-1.

PMID- 12228383
TI  - Carbon, Nitrogen, and Nutrient Interactions in Beta vulgaris L. as Influenced by
      Nitrogen Source, NO3- versus NH4+
AB  - Sugar beets (Beta vulgaris L. cv F58-554H1) were grown hydroponically in a 16-h
      light, 8-h dark period (photosynthetic photon flux density of 0.5 mmol m-2 s-1)
      for 4 weeks from sowing in half-strength Hoagland nutrient solution containing
      7.5 mM nitrate. Half of the plants were then transferred to 7.5 mM ammonium N;
      the rest remained in solution with 7.5 mM nitrate N. Upon transfer from nitrate
      to ammonium, the total N concentration decreased sharply in the fibrous roots and
      petiole/midribs and increased substantially in the leaf blades. This was because
      of the decreased nitrate concentrations in fibrous roots and petioles and a
      concomitant increase in amino acid/amide-N and protein N in leaf blades. Sugar
      beets acclimated to ammonium partly by a 2.5-fold increase in glutamine synthase
      activity in fibrous roots and a 1.7-fold increase in leaf blades. Rapid ammonium
      assimilation into glutamine consumed carbon skeletons, leading to a depletion of
      foliar starch, sucrose, and maltose. Ammonium treatment stimulated activities of
      some glycolytic/Krebs cycle enzymes, e.g. pyruvate dehydrogenase. Nitrate-fed
      leaf blades contained substantially larger concentrations of osmolytes (i.e.
      nitrate, cations, and sucrose), which may have contributed to the faster rates of
      leaf expansion in nitrate-fed compared to ammonium-fed plants.

PMID- 12228384
TI  - The Effects of Chilling in the Light on Ribulose-1,5-Bisphosphate
      Carboxylase/Oxygenase Activation in Tomato (Lycopersicon esculentum Mill.).
AB  - Photosynthesis rate, ribulsoe-1,5-bisphosphate carboxylase/oxygenase (Rubisco)
      activation state, and ribulose bisphosphate concentration were reduced after
      exposing tomato (Lycopersicon esculentum Mill.) plants to light at 4[deg]C for 6
      h. Analysis of lysed and reconsituted chloroplasts showed that activity of the
      thylakoid membrane was inhibited and that Rubisco, Rubisco activase, and other
      soluble factors were not affected. Leaf photosynthesis rates and the ability of
      chilled thylakoid membranes to promote Rubisco activation recovered after 24 h at
      25[deg]C. Thylakoid membranes from control tomato plants were as effective as
      spinach thylakoids in activating spinach Rubisco in the presence of spinach
      Rubisco activase. This observation is in sharp contrast to the poor ability of
      spinach Rubisco activase to activate tomato Rubisco (Z.-Y. Wang, G.W. Snyder,
      B.D. Esau, A.R. Portis, and W.L. Ogren [1992] Plant Physiol 100: 1858-1862). The
      ability of thylakoids from chilled tomato plants to activate Rubisco in the assay
      system was greatly inhibited compared to control plants. These experiments
      indicate that chilling tomato plants at 4[deg]C interferes with photosynthetic
      carbon metabolism at two sites, thioredoxin/ferredoxin reduction (G.F.
      Sassenrath, D.R. Ort, and A.R. Portis, Jr. [1990] Arch Biochem Biophys 282: 302
      308), which limits bisphosphatase activity, and Rubisco activase, which reduces
      Rubisco activation state.

PMID- 12228385
TI  - Analysis of Sweet cherry (Prunus avium L.) Leaves for Plant Signal Molecules That
      Activate the syrB Gene Required for Synthesis of the Phytotoxin, Syringomycin, by
      Pseudomonas syringae pv syringae.
AB  - An important aspect of the interaction of Pseudomonas syringae pv syringae with
      plant hosts is the perception of plant signal molecules that regulate expression
      of genes, such as syrB, required for synthesis of the phytotoxin, syringomycin.
      In this study, the leaves of sweet cherry (Prunus avium L.) were analyzed to
      determine the nature of the syrB-inducing activity associated with tissues of a
      susceptible host. Crude leaf extracts yielded high amounts of total signal
      activity of more than 12,000 units g-1 (fresh weight) based on activation of a
      syrB-lacZ fusion in strain B3AR132. The signal activity was fractionated by C18
      reversed-phase high-performance liquid chromatography and found to be composed of
      phenolic glycosides, which were resolved in three regions of the high-performance
      liquid chromatography profile, and sugars, which eluted with the void volume. Two
      flavonol glycosides, quercetin 3-rutinosyl-4[prime]-glucoside and kaempferol 3
      rutinosyl-4[prime]-glucoside, and a flavanone glucoside, dihydrowogonin 7
      glucoside, were identified. The flavonoid glycosides displayed similar specific
      signal activities and were comparable in signal activity to arbutin, a phenyl
      [beta]-glucoside, giving rise to between 120 and 160 units of [beta]
      galactosidase activity at 10 [mu]M. Although D-fructose exhibits intrinsic low
      level syrB-inducing signal activity, D-fructose enhanced by about 10-fold the
      signal activities of the flavonoid glycosides at low concentrations (e.g. 10
      [mu]M). This demonstrates that flavonoid glycosides, which represent a new class
      of phenolic plant signals sensed by P. s. syringae, are in sufficient quantities
      in the leaves of P. avium to activate phytotoxin synthesis.

PMID- 12228386
TI  - 1 L-myo-Inositol 1-Phosphate Synthase from Arabidopsis thaliana.
AB  - A recombinant phage containing an Arabidopsis thaliana cDNA sequence encoding a
      protein with 1L-myo-inositol 1-phosphate synthase (EC 5.5.1.4) activity has been
      isolated and used for transcriptional and translational studies. The
      identification of the recombinant phage relied on the observations that (a) the
      clone complements a mutation in the structural gene for 1L-myo-inositol 1
      phosphate synthase in the yeast Saccharomyces cerevisiae, (b) the in vitro
      synthesized polypeptide enzymatically converts glucose 6-phosphate into inositol
      1-phosphate, (c) in vitro transcription and translation of this cDNA sequence
      produces a polypeptide that is recognized by anti-yeast myo-inositol 1-phosphate
      synthase antiserum, and (d) inositol regulates the expression of the
      corresponding gene in Arabidopsis.

PMID- 12228387
TI  - Salt Tolerance of Glycinebetaine-Deficient and -Containing Maize Lines.
AB  - Pairs of homozygous near-isogenic glycinebetaine-containing (Bet1/Bet1) and 
      deficient (bet1/bet1) F8 lines of Zea mays L. (maize) were tested for differences
      in salt (150 mM NaCl or 127.25 mM NaCl plus 22.5 mM CaCl2) tolerance. The
      Bet1/Bet1 lines exhibited less shoot growth inhibition (as measured by dry matter
      accumulation, leaf area expansion rate and/or, plant height extension rate) under
      salinized conditions in comparison to their nearisogenic bet1/bet1 sister lines.
      These growth differences were associated with maintenance of a significantly
      higher leaf relative water content, a higher rate of carbon assimilation, and a
      greater turgor in Bet1/Bet1 lines than in bet1/bet1 lines under salinized
      conditions. These results strongly suggest that a single gene conferring
      glycinebetaine accumulation (and/or a tightly linked locus) plays a key role in
      osmotic adjustment in maize.

PMID- 12228388
TI  - Steroid Hormones Stimulate Germination and Tube Growth of in Vitro Matured
      Tobacco Pollen.
AB  - A study of the effects of different steroids on germination and tube growth of
      tobacco pollen (Nicotiana tabacum L. cv Petit Havana SR1) matured in vitro is
      presented. Application of the mammalian steroid sex hormones (testosterone,
      progesterone, and estradiol) resulted in a stimulation of pollen germination and
      tube elongation. The presence of both steroids and flavonols in the germination
      medium strongly enhanced the growth of tobacco male gametophytes.

PMID- 12228389
TI  - Decrease in Activity of Glutathione Reductase Enhances Paraquat Sensitivity in
      Transgenic Nicotiana tabacum.
AB  - Transgenic tobacco (Nicotiana tabacum L. cv SR1) with decreased activity of
      glutathione reductase exhibited enhanced sensitivity to paraquat in the light as
      evaluated by chlorophyll destruction and electrolyte leakage from leaf discs.
      This result indicates the involvement of glutathione reductase in the tolerance
      of plants to photooxidative stress caused by the herbicide.

PMID- 12228390
TI  - What Controls the Amount and Structure of Starch in Storage Organs?

PMID- 12228391
TI  - How and Why Do Plants Inactivate Homologous (Trans)genes?

PMID- 12228392
TI  - Photosystem II Excitation Pressure and Development of Resistance to
      Photoinhibition (I. Light-Harvesting Complex II Abundance and Zeaxanthin Content
      in Chlorella vulgaris).
AB  - The basis of the increased resistance to photoinhibition upon growth at low
      temperature was investigated. Photosystem II (PSII) excitation pressure was
      estimated in vivo as 1 - qp (photochemical quenching). We established that
      Chlorella vulgaris exposed to either 5[deg]C/150 [mu]mol m-2 s-1 or 27[deg]C/2200
      [mu]mol m-2 s-1 experienced a high PSII excitation pressure of 0.70 to 0.75. In
      contrast, Chlorella exposed to either 27[deg]C/150 [mu]mol m-2 s-1 or 5[deg]C/20
      [mu]mol m-2 s-1 experienced a low PSII excitation pressure of 0.10 to 0.20.
      Chlorella grown under either regime at high PSII excitation pressure exhibited:
      (a) 3-fold higher light-saturated rates of O2 evolution; (b) the complete
      conversion of PSII[alpha] centers to PSII[beta] centers; (c) a 3-fold lower
      epoxidation state of the xanthophyll cycle intermediates; (d) a 2.4-fold higher
      ratio of chlorophyll a/b; and (e) a lower abundance of light-harvesting
      polypeptides than Chlorella grown at either regime at low PSII excitation
      pressure. In addition, cells grown at 5[deg]C/150 [mu]mol m-2 s-1 exhibited
      resistance to photoinhibition comparable to that of cells grown at 27[deg]C/2200
      [mu]mol m-2 s-1 and were 3- to 4-fold more resistant to photoinhibition than
      cells grown at either regime at low excitation pressure. We conclude that
      increased resistance to photoinhibition upon growth at low temperature reflects
      photosynthetic adjustment to high excitation pressure, which results in an
      increased capacity for nonradiative dissipation of excess light through
      zeaxanthin coupled with a lower probability of light absorption due to reduced
      chlorophyll per cell and decreased abundance of light-harvesting polypeptides.

PMID- 12228393
TI  - Identification of Endogenous Gibberellins in Petunia Flowers (Induction of
      Anthocyanin Biosynthetic Gene Expression and the Antagonistic Effect of Abscisic
      Acid).
AB  - The elongation and pigmentation of corollas of Petunia hybrida requires the
      presence of anthers. The ability of exogenous gibberellic acid (GA3) to
      substitute for the anthers suggests a role for endogenous GAs. Here we report the
      identification of endogenous GAs in corollas and in anthers and show that both
      tissues contain detectable levels of GA1, GA4, and GA9, of which GA4 is the most
      abundant. These GAs stimulate corolla pigmentation, chalcone synthase (chs) mRNA
      accumulation, and chs transcription in an in vitro flower bud culture system.
      Methyl ester derivatives of GA3 and GA4 were not active but did not inhibit the
      bioactive GAs. Even though it is unknown whether abscisic acid (ABA) is involved
      in corolla maturation, ABA inhibited pigmentation of intact flowers, overruling
      the effect of the anthers. In detached flower buds it was shown that ABA
      prevented activation of the chs promoter by GA3. The synthesis of anthocyanin
      pigments requires the coordinate expression of at least 15 structural genes.
      Expression of early biosynthetic genes and of late biosynthetic genes are
      regulated by different transcriptional activators. GA induces both classes of
      genes with similar kinetics, indicating that GA acts relatively early in the
      signaling pathway.

PMID- 12228394
TI  - Synechococcus sp. PCC7942 Transformed with Escherichia coli bet Genes Produces
      Glycine Betaine from Choline and Acquires Resistance to Salt Stress.
AB  - Synechococcus sp. PCC7942, a fresh water cyanobacterium, was transformed by a
      shuttle plasmid that contains a 9-kb fragment encoding the Escherichia coli bet
      gene cluster, i.e. betA (choline dehydrogenase), betB (betaine aldehyde
      dehydrogenase), betI (a putative regulatory protein), and betT (the choline
      transport system). The expression of these genes was demonstrated in the
      cyanobacterial cells (bet-containing cells) by northern blot analysis, as well as
      by the detection of glycine betaine by 1H nuclear magnetic resonance in cells
      supplemented with choline. Endogenous choline was not detected in either control
      or bet-containing cells. Both control and bet-containing cyanobacterial cells
      were found to import choline in an energy-dependent process, although this import
      was restricted only to bet-containing cells in conditions of salt stress. Glycine
      betaine was found to accumulate to a concentration of 45 mM in bet-containing
      cyanobacterial cells, and this resulted in a stabilization of the photosynthetic
      activities of photosystems I and II, higher phycobilisome contents, and general
      protective effects against salt stress when compared to control cells. The growth
      of bet-containing cells was much faster in the presence of 0.375 M NaCl than that
      of control cells, indicating that the transformant acquired resistance to salt
      stress.

PMID- 12228395
TI  - Stability of the Apoproteins of Light-Harvesting Complex I and II during
      Biogenesis of Thylakoids in the Chlorophyll b-less Barley Mutant Chlorina f2.
AB  - Transcription and translation of Lhc (cab) genes have been compared in the
      chlorina f2 mutant of barley (Hordeum vulgare) and its wild type to study the
      effect of chlorophyll b's absence on the regulation of assembly of the light
      harvesting complexes (LHC). All tested genes were transcribed and the amount of
      their respective mRNAs increased rhythmically upon illumination of etiolated
      mutant plants. The synthesis of individual LHC apoproteins also had a rhythmic
      pattern when total leaf protein extracts were examined, whereas they increased
      gradually in the thylakoid. Only some LHC pigment-proteins present in wild-type
      thylakoids were found in mature mutant membranes. Thus, only the 25-kD (type 3)
      apoprotein of the three apoproteins of the major LHC IIb complex survived. The
      amount of the minor LHC II pigment-proteins was considerably reduced but not to
      zero. Photosystem I had some of the two LHC la apoproteins but had little of
      those of LHC lb. This was reflected in a shift of the 77-K emission maximum of
      whole leaves from 741 to 732 nm. It is concluded that the two largest LHC IIb and
      the LHC Ib apoproteins need chlorophyll b for stable integration into the
      membrane and that posttranslational regulation plays a major role in LHC
      assembly.

PMID- 12228396
TI  - A Novel Class of Herbicides (Specific Inhibitors of Imidazoleglycerol Phosphate
      Dehydratase).
AB  - A new mode of herbicidal action was established by finding specific inhibitors of
      imidazoleglycerol phosphate dehydratase, an enzyme of histidine (His)
      biosynthesis. Three triazole phosphonates inhibited the reaction of the enzyme
      with Ki values of 40 [plus or minus] 6.5, 10 [plus or minus] 1.6, and 8.5 [plus
      or minus] 1.4 nM, respectively, and were highly cytotoxic to cultured plant
      cells. This effect was completely reversed by the addition of His, proving that
      the cytotoxicity was primarily caused by the inhibition of His biosynthesis.
      These inhibitors showed wide-spectrum, postemergent herbicidal activity at
      application rates ranging from 0.05 to 2 kg/ha.

PMID- 12228397
TI  - Effects of Iron Excess on Nicotiana plumbaginifolia Plants (Implications to
      Oxidative Stress).
AB  - Fe excess is believed to generate oxidative stress. To contribute to the
      understanding of Fe metabolism, Fe excess was induced in Nicotiana
      plumbaginifolia grown in hydroponic culture upon root cutting. Toxicity symptoms
      leading to brown spots covering the leaf surface became visible after 6 h.
      Photosynthesis was greatly affected within 12 h; the photosynthetic rate was
      decreased by 40%. Inhibition of photosynthesis was accompanied by
      photoinhibition, increased reduction of photosystem II, and higher thylakoid
      energization. Fe excess seemed to stimulate photorespiration because catalase
      activity doubled. To cope with cellular damage, respiration rate increased and
      cytosolic glucose-6-phosphate dehydrogenase activity more than doubled.
      Simultaneously, the content of free hexoses was reduced. Indicative of generation
      of oxidative stress was doubling of ascorbate peroxidase activity within 12 h.
      Contents of the antioxidants ascorbate and glutathione were reduced by 30%,
      resulting in equivalent increases of dehydroascorbate and oxidized glutathione.
      Taken together, moderate changes in leaf Fe content have a dramatic effect on
      plant metabolism. This indicates that cellular Fe concentrations must be finely
      regulated to avoid cellular damage most probably because of oxidative stress
      induced by Fe.

PMID- 12228398
TI  - Factors Affecting the Enhancement of Oxidative Stress Tolerance in Transgenic
      Tobacco Overexpressing Manganese Superoxide Dismutase in the Chloroplasts.
AB  - Two varieties of tobacco (Nicotiana tabacum var PBD6 and var SR1) were used to
      generate transgenic lines overexpressing Mn-superoxide dismutase (MnSOD) in the
      chloroplasts. The overexpressed MnSOD suppresses the activity of those SODs
      (endogenous MnSOD and chloroplastic and cytosolic Cu/ZnSOD) that are prominent in
      young leaves but disappear largely or completely during aging of the leaves. The
      transgenic and control plants were grown at different light intensities and were
      then assayed for oxygen radical stress tolerance in leaf disc assays and for
      abundance of antioxidant enzymes and substrates in leaves. Transgenic plants had
      an enhanced resistance to methylviologen (MV), compared with control plants, only
      after growth at high light intensities. In both varieties the activities of
      FeSOD, ascorbate peroxidase, dehydroascorbate reductase, and monodehydroascorbate
      reductase and the concentrations of glutathione and ascorbate (all expressed on a
      chlorophyll basis) increased with increasing light intensity during growth. Most
      of these components were correlated with MV tolerance. It is argued that SOD
      overexpression leads to enhancement of the tolerance to MV-dependent oxidative
      stress only if one or more of these components is also present at high levels.
      Furthermore, the results suggest that in var SR1 the overexpressed MnSOD enhances
      primarily the stromal antioxidant system.

PMID- 12228399
TI  - Zinc Requirement for Stomatal Opening in Cauliflower.
AB  - Zn deficiency induced increases in epicuticular wax deposits, lamina thickness,
      degree of succulence, water saturation deficit, diffusive resistance, and proline
      accumulation and decreases in carbonic anhydrase activity, water potential,
      stomatal aperture, and transpiration in the leaves of cauliflower (Brassica
      oleracea L. var botrytis cv Pusa) plants. Restoration of Zn supply to the
      deficient plants increased stomatal aperture, transpiration, and carbonic
      anhydrase activity significantly within 2 h. However, leaf water potential in the
      Zn-deficient plants did not recover within 24 h after resupply of Zn. The guard
      cells in epidermal peels from the Zn-deficient leaves had less K+ than those from
      the controls. Stomatal aperture in the epidermal peels from Zn-deficient leaves
      was 64% less than in the controls when the epidermal strips were floated on 125
      mM KCl. Supplementing the ambient medium 25 mM KCl with ZnCl2 enhanced stomatal
      aperture in both control and Zn-deficient peels, and the effect was significant
      in the latter. The observations indicate involvement of Zn in stomatal opening,
      possibly as a constituent of carbonic anhydrase needed for maintaining adequate
      [HCO3-] in the guard cells, and also as a factor affecting K+ uptake by the guard
      cells.

PMID- 12228400
TI  - Immunolocalization of a Unique Form of Maize Kernel Glutamine Synthetase Using a
      Monoclonal Antibody.
AB  - The pedicel (basal maternal tissue) of maize (Zea mays L.) kernels contains a
      physically and kinetically unique form of glutamine synthetase (GSp1) that is
      involved in the conversion of transport forms of nitrogen into glutamine for
      uptake by the developing endosperm (M.J. Muhitch [1989] Plant Physiol 91: 868
      875). A monoclonal antibody has been raised against this kernel-specific GS that
      does not cross-react either with a second GS isozyme found in the pedicel or with
      the GS isozymes from the embryo, roots, or leaves. When used as a probe for
      tissue printing, the antibody labeled the pedicel tissue uniformly and also
      labeled some of the pericarp surrounding the lower endosperm. Silver-enhanced
      immunogold staining of whole-kernel paraffin sections revealed the presence of
      GSp1 in both the vascular tissue that terminates in the pedicel and the pedicel
      parenchyma cells, which are located between the vascular tissue and the basal
      endosperm transfer cells. Light staining of the subaleurone was also noted. The
      tissue-specific localization of GSp1 within the pedicel is consistent with its
      role in the metabolism of nitrogenous transport compounds as they are unloaded
      from the phloem.

PMID- 12228401
TI  - Differential Accumulation of Sunflower Tetraubiquitin mRNAs during Zygotic
      Embryogenesis and Developmental Regulation of Their Heat-Shock Response.
AB  - We have isolated and sequenced Ha UbiS, a cDNA for a dry-seed-stored mRNA that
      encodes tetraubiquitin. We have observed differential accumulation of
      tetraubiquitin mRNAs during sunflower (Helianthus annuus L.) zygotic
      embryogenesis. These mRNAs were up-regulated during late embryogenesis and
      reached higher prevalence in the dry seed, where they were found to be associated
      mainly with provascular tissue. UbiS mRNA, as confirmed by Rnase A protection
      experiments, accumulated also in response to heat shock, but only in leaves and
      later during postgerminative development. These novel observations demonstrate
      expression during seed maturation of specific plant polyubiquitin transcripts and
      developmental regulation of their heat-shock response. Using ubiquitin antibodies
      we also detected discrete, seed-specific proteins with distinct temporal
      expression patterns during zygotic embryogenesis. Some of these patterns were
      concurrent with UbiS mRNA accumulation in seeds. The most abundant ubiquitin
      reacting proteins found in mature seeds were small (16-22 kD) and acidic
      (isoelectric points of 6.1-7.4). Possible functional implications for UbiS
      expression elicited from these observations are discussed.

PMID- 12228402
TI  - In Vivo Regulation of Wheat-Leaf Phosphoenolpyruvate Carboxylase by Reversible
      Phosphorylation.
AB  - Regulation of C3 phosphoenolpyruvate carboxylase (PEPC) and its protein
      serine/threonine kinase (PEPC-PK) was studied in wheat (Triticum aestivum) leaves
      that were excised from low-N-grown seedlings and subsequently illuminated and/or
      supplied with 40 mM KNO3. The apparent phosphorylation status of PEPC was
      assessed by its sensitivity to L-malate inhibition at suboptimal assay
      conditions, and the activity state of PEPC-PK was determined by the in vitro 32P
      labeling of purified maize dephospho-PEPC by [[gamma]-32P]ATP/Mg. Illumination
      ([plus or minus]NO3-) for 1 h led to about a 4.5-fold increase in the 50%
      inhibition constant for L-malate, which was reversed by placing the illuminated
      detached leaves in darkness (minus NO3-). A 1 -h exposure of excised leaves to
      light, KNO3, or both resulted in relative PEPC-PK activities of 205, 119, and
      659%, respectively, of the dark/0 mM KNO3 control tissue. In contrast, almost no
      activity was observed when a recombinant sorghum phosphorylation-site mutant
      (S8D) form of PEPC was used as protein substrate in PEPC-PK assays of the light
      plus KNO3 leaf extracts. In vivo labeling of wheat-leaf PEPC by feeding 32P
      labeled orthophosphate showed that PEPC from light plus KNO3 tissue was
      substantially more phosphorylated than the enzyme in the dark minus-nitrate
      immunoprecipitates. Immunoblot analysis indicated that no changes in relative
      PEPC-protein amount occurred within 1 h for any of the treatments. Thus, C3 PEPC
      activity in these detached wheat leaves appears to be regulated by
      phosphorylation of a serine residue near the protein's N terminus by a Ca2+ 
      independent protein kinase in response to a complex interaction in vivo between
      light and N.

PMID- 12228403
TI  - Role of the Differentiation of Root Epidermal Cells in Nod Factor (from Rhizobium
      meliloti)-Induced Root-Hair Depolarization of Medicago sativa.
AB  - The stage of differentiation of epidermal cells and the development of root hairs
      was found to be important for the induction of depolarization in root hairs of
      Medicago sativa by Nod factor [NodRm-IV(S)] isolated from the bacterium Rhizobium
      meliloti. The electrical membrane response was concentration dependent, having
      its major effect (amplitude of the depolarization and number of root hairs that
      responded) at 10-8 and 10-7 M Nod factor. This response was correlated with a
      morphological effect of Nod factor in the root-hair-deformation bioassay at
      similar concentrations. The effect of Nod factor on depolarization and root-hair
      deformation showed specificity with respect to the structure, since unsulfated
      Nod molecules were inactive, as was the synthetic N,N',N",N"'-
      tetraacetylchitotetraose. The Nod factor that is O-acetylated at the nonreducing
      sugar was as efficient in root-hair deformation and membrane depolarization as
      the sulfated Nod factor.

PMID- 12228404
TI  - Regulation of Nitrite Reductase Activity under CO2 Limitation in the
      Cyanobacterium Synechococcus sp. PCC7942.
AB  - During photoautotrophic growth under CO2-limited conditions, cells of
      Synechococcus sp. PCC7942 excreted into the medium about 30% of the nitrite
      produced by reduction of nitrate. No nitrite was excreted under CO2-sufficient
      conditions. After transfer of high-CO2-grown cells to CO2-limited conditions,
      nitrite reductase activity started to decline within 0.5 h and decreased to 50%
      of the initial level in 3 h, whereas nitrate reductase activity was virtually
      unchanged. Nitrite started to accumulate in the medium about 3 h after the
      transfer of the cells to CO2-limited conditions and reached a concentration of
      >0.4 mM at 17 h. These findings suggested that the nitrite excretion was due to
      an imbalance of the activities of nitrite reductase and nitrate reductase. Since
      ammonium, the product of nitrite reduction, was not detected in the medium, it
      was concluded that the step of nitrite reduction limits the rate of nitrate
      assimilation under CO2-limited conditions. The extent of decrease in nitrite
      reductase activity under CO2-limited conditions was much larger than that caused
      by rifampicin (an inhibitor of RNA synthesis) treatment under high-CO2
      conditions. Addition of CO2, in the form of sodium bicarbonate, to the CO2
      limited culture increased the nitrite reductase activity, but rifampicin
      inhibited this increase. These findings suggested the presence of a mechanism
      that irreversibly inactivates nitrite reductase under CO2-limited conditions.

PMID- 12228405
TI  - Isolation and Characterization of Mutants of Thiophene Synthesis in Tagetes
      erecta.
AB  - Two mutants of Tagetes erecta displaying aberrant thiophene composition were
      identified by screening more than 300 plants from a mutagenized M2 population
      using high-performance liquid chromatography analysis of root extracts. Both
      mutants, which may have originated from the same mutational event, contained high
      amounts of the C13 monothiophene 2-(but-3-en-1-ynyl)-5-(penta-1,3-diynyl)
      thiophene that was previously not found in T. erecta and also high amounts of two
      C13 bithienyls that were absent or present at low concentrations in the wild
      type. The mutant phenotype was also expressed in 21 Agrobacterium rhizogenes
      transformed root clones derived from both mutants. Feeding experiments with root
      cultures derived from one mutant and from the wild type indicated that the
      monothiophene accumulating in the mutant is the common precursor for all
      bithienyl thiophenes in wild-type and mutant Tagetes erecta. These experiments
      also showed that one mutant is deficient in demethylation of the monothiophene.

PMID- 12228406
TI  - C4 Photosynthesis (The Effects of Leaf Development on the CO2-Concentrating
      Mechanism and Photorespiration in Maize).
AB  - The effect of O2 on photosynthesis was determined in maize (Zea mays) leaves at
      different developmental stages. The optimum level of O2 for maximum
      photosynthetic rates was lower in young and senescing tissues (2-5 kPa) than in
      mature tissue (9 kPa). Inhibition of photosynthesis by suboptimal levels of O2
      may be due to a requirement for functional mitochondria or to cyclic/pseudocyclic
      photophosphorylation in chloroplasts; inhibition by supraoptimal levels of O2 is
      considered to be due to photorespiration. Analysis of a range of developmental
      stages (along the leaf blade and at different leaf ages and positions) showed
      that the degree of inhibition of photosynthesis by supraoptimal levels of O2
      increased rapidly once the ribulose-1,5-bisphosphate carboxylase/oxygenase and
      chlorophyll contents were below a critical level and was similar to that of C3
      plants. Tissue having a high sensitivity of photosynthesis to O2 may be less
      effective in concentrating CO2 in the bundle sheath cells due either to limited
      function of the C4 cycle or to higher bundle sheath conductance to CO2. An
      analysis based on the kinetic properties of ribulose-1,5-bisphosphate
      carboxylase/oxygenase was used to predict the maximum CO2 level concentrated in
      bundle sheath cells at a given degree of inhibition of photosynthesis by
      supraoptimal levels of O2.

PMID- 12228407
TI  - Purification of Hemoglobin from the Actinorhizal Root Nodules of Myrica gale L.
AB  - Hemoglobins are generally absent or present in low concentrations in the nodules
      of actinorhizal plants. An exception is Casuarina, where a hemoglobin occurs at
      relatively high concentration. However, this plant is unique in that Frankia, the
      microsymbiont, lacks the vesicles that are normally the site of nitrogen
      fixation. The present paper shows that a hemoglobin also occurs at high
      concentrations in Myrica gale L., an actinorhizal plant in which Frankia does
      form vesicles. Hemoglobin was extracted from root nodules under anaerobic
      conditions using a buffer containing CO, detergent, and a reducing agent.
      Carboxyhemoglobin was purified using gel filtration followed by aerobic ion
      exchange chromatography. The optical absorption spectra of the oxy-, deoxy-, and
      carboxyhemoglobins were similar to those of other hemoglobins. The molecular mass
      of the native hemoglobin estimated by gel filtration was 38,500 D. The molecular
      mass of the subunits estimated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis was 16,200 D, consistent with the mass of other hemoglobin
      subunits. Thus, the native hemoglobin is probably a dimer.

PMID- 12228408
TI  - Fate of Nodule-Specific Polysaccharide Produced by Bradyrhizobium japonicum
      Bacteroids.
AB  - A polysaccharide produced by Bradyrhizobium japonicum bacteroids in nodules (NPS)
      on soybean (Glycine max [L.] Merr.) roots is different in composition and
      structure from the extracellular polysaccharide produced in culture by this
      organism. Isogenic strains either capable or incapable of NPS synthesis supported
      similar rates of plant growth and nitrogenase activity, indicating that
      polysaccharide deposition was not detrimental. The possibility that NPS may have
      some protective or nutritional role for bacteroids was considered. Analysis of
      disintegrating nodules over periods of 1 to 3 months indicated greater recovery
      of viable bacteria from NPS+ nodules prior to the breakdown of NPS. During and
      after the breakdown of NPS, the decline in viable bacteria was similar for NPS+
      and NPS- strains. Bacteroid destruction in senescing nodules may be accelerated
      by exposure to proteolytic enzymes in host cytoplasm; however, highly purified
      NPS had no significant effect on the in vitro activity of partially purified
      proteases, so protection of bacteroids via this mechanism is unlikely. B.
      japonicum USDA 438 did not utilize NPS as a carbon source for growth in liquid
      culture. In vitro assays of NPS depolymerase activity in cultured bacteria and
      bacteroids were negative using a variety of strains, all of which contained
      extracellular polysaccharide depolymerase. It seems highly unlikely that B.
      japonicum can utilize the polysaccharide it synthesizes in nodules, and NPS
      breakdown in senescing nodules is probably caused by saprophytic fungi.

PMID- 12228409
TI  - Arginine Decarboxylase and Putrescine Oxidase in Ovaries of Pisum sativum L.
      (Changes during Ovary Senescence and Early Stages of Fruit Development).
AB  - Enzymatic activities involved in putrescine metabolism in ovaries of Pisum
      sativum L. during ovary senescence and fruit set were investigated. Accumulation
      of putrescine was observed during incubation of extracts from gibberellic acid
      treated unpollinated ovaries (young developing fruits) but not in extracts from
      untreated ovaries (senescent ovaries). Extracts from pea ovaries showed arginine
      decarboxylase (ADC) activity, but ornithine decarboxylase and arginase activity
      were not detected. ADC activity decreased in presenescent ovaries and increased
      markedly after induction of fruit set with gibberellic acid. Increases in ADC
      activity were also observed with application of other plant growth substances
      (benzy-ladenine and 2,4-dichlorophenoxyacetic acid), after pollination, and in
      the slender (la crys) pea mutant. By contrast, putrescine oxidase activity
      increased in presenescent ovaries but did not increase during early fruit
      development. All of these results suggest that ADC and putrescine oxidase are
      involved in the control of putrescine metabolism. Ovary senescence is
      characterized by the absence of putrescine biosynthesis enzymes and increased
      levels of putrescine oxidase and fruit development by an increase in ADC and a
      constant level of putrescine oxidase.

PMID- 12228410
TI  - Chloroplast Response in Dunaliella salina to Irradiance Stress (Effect on
      Thylakoid Membrane Protein Assembly and Function).
AB  - The chloroplast response in the green alga Dunaliella salina to irradiance stress
      was investigated. Cells were grown under low light (LL) at 100 [mu]mol photons m
      2 s-1 or high light (HL) at 2000 [mu]mol photons m-2 s-1 incident intensity. LL
      grown cells had a low chlorophyll (Chl) a/b ratio, an abundance of light
      harvesting complex II proteins (LHC-II), and a large Chl antenna size. HL-grown
      cells had a higher Chl a/b ratio, relatively fewer LHC-II, and a small Chl
      antenna size. The more abundant higher molecular mass subunits of the LHC-II
      (approximately 31 kD) were selectively depleted from the thylakoid membrane of HL
      grown cells. Light-shift experiments defined the kinetics of change in the
      subunit composition of the LHC-II and suggested distinct mechanisms in the
      acclimation of thylakoids to HL or LL conditions. The results showed that
      irradiance exerts a differential regulation on the expression of various Lhcb
      genes. The specific polyclonal antibodies used in this work, raised against the
      purified LHC-II, cross-reacted with a polypeptide of approximately 20 kD in HL
      grown samples. In this work we examined the dynamics of induction of this novel
      protein and discuss its function in terms of a chloroplast response to the level
      of irradiance.

PMID- 12228411
TI  - Cold-Induced Accumulation of hsp90 Transcripts in Brassica napus.
AB  - Characterization of the expression of hsp90 genes of Brassica napus by northern
      blot analysis and immunoblotting showed that the hsp90 mRNA and protein are
      present in all B. napus tissues examined, albeit at different levels. High levels
      of hsp90 mRNA and protein were found in young and rapidly dividing tissues such
      as shoot apices and flower buds, suggesting that hsp90 may have an important role
      in plant growth and development. A significant increase in hsp90 mRNA levels was
      detected in seedlings exposed to 5[deg]C. The transcript levels reached a maximum
      within 1 d of cold treatment and remained elevated for the entire duration of
      cold treatment. The levels of hsp90 mRNA rapidly decreased to the level found in
      control plants upon return to 20[deg]C. The cold-induced accumulation of hsp90
      mRNA closely resembles the expression of two previously identified cold-regulated
      genes of B. napus. We have also confirmed cold regulation of hsp90 mRNA in
      spinach (Spinacea oleracea). Our results suggest a role for hsp90 in adaptation
      to cold temperature stress.

PMID- 12228412
TI  - Developmental Regulation of Respiratory Activity in Pea Leaves.
AB  - The developmental pattern of mitochondrial respiratory activity in pea (Pisum
      sativum) leaves has been investigated in an attempt to determine changes in
      mitochondrial function as plant cells mature. NADH and succinate dehydrogenase
      and cytochrome c oxidase activities remained relatively constant during cell
      maturation (from d 0 to d 14). Alternative oxidase and glycine decarboxylase
      activity, however, were low in young leaf tissue (d 0-6) but increased
      substantially as the tissue matured (d 7-14) and gained photorespiratory
      activity. Western blot analysis of the alternative oxidase protein revealed that
      it was primarily in an oxidized state in young leaves (d 0-6) but switched
      dramatically to the reduced form of the protein as the pea cells matured (d 7
      14). The switch to the reduced form of the protein correlated with an increase in
      alternative oxidase activity. Results are discussed in terms of the changing
      function of plant mitochondria during leaf development.

PMID- 12228413
TI  - RNA-Binding Characteristics of a Ribonucleoprotein from Spinach Chloroplast.
AB  - A chloroplast (nuclear-encoded) RNA-binding protein (28RNP) was previously
      purified from spinach (Spinacia oleracea). This 28RNP was found to be the major
      RNA-binding protein co-purified during the isolation scheme of 3[prime] end RNA
      processing activity of several chloroplastic genes. To learn more about the
      possible involvement of 28RNP in the 3[prime] end RNA-processing event, we
      investigated the RNA-binding properties and the location of the protein in the
      chloroplast. We found that recombinant Escherichia coliexpressed 28RNP binds with
      apparently the same affinity to every chloroplastic 3[prime] end RNA that was
      analyzed, as well as to RNAs derived from the 5[prime] end or the coding region
      of some chloroplastic genes. Differences in the RNA-binding affinities for some
      chloroplastic 3[prime] end RNAs were observed when the recombinant 28RNP was
      compared with the "native" 28RNP in the chloroplast-soluble protein extract. In
      addition, we found that the 28RNP is not associated with either thylakoid-bound
      or soluble polysomes in which a great portion of the chloroplast rRNA and mRNA
      are localized. These results suggest that the native 28RNP binds specifically to
      certain RNA molecules in the chloroplast in which other components (possibly
      proteins) and/or posttranslational modifications are involved in determining RNA
      binding specificity of the 28RNP.

PMID- 12228414
TI  - Photosystem II Regulation and Dynamics of the Chloroplast D1 Protein in
      Arabidopsis Leaves during Photosynthesis and Photoinhibition.
AB  - Arabidopsis thaliana leaves were examined in short-term (1 h) and long-term (10
      h) irradiance experiments involving growth, saturating and excess light. Changes
      in photosynthetic and chlorophyll fluorescence parameters and in populations of
      functional photosystem II (PSII) centers were independently measured. Xanthophyll
      pigments, 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU)-binding sites, the
      amounts of D1 protein, and the rates of D1 protein synthesis were determined.
      These comprehensive studies revealed that under growth or light-saturating
      conditions, photosynthetic parameters remained largely unaltered. Photoprotection
      occurred at light saturation indicated by a dark-reversible increase in non
      photochemical quenching accompanied by a 5-fold increase in antheraxanthin and
      zeaxanthin. No consistent change in the concentrations of functional PSII
      centers, DCMU-binding sites, or D1 protein pool size occurred. D1 protein
      synthesis was rapid. In excess irradiance, quantum yield of O2 evolution and the
      efficiency of PSII were reduced, associated with a 15- to 20-fold increase in
      antheraxanthin and zeaxanthin and a sustained increase in nonphotochemical
      quenching. A decrease in functional PSII center concentration occurred, followed
      by a decline in the concentration of D1 protein; the latter, however, was not
      matched by a decrease in DCMU-binding sites. In the most extreme treatments, DCMU
      binding site concentration remained 2 times greater than the concentration of D1
      protein recognized by antibodies. D1 protein synthesis rates remained unaltered
      at excess irradiances.

PMID- 12228415
TI  - Plant Microsomal Phospholipid Acyl Hydrolases Have Selectivities for Uncommon
      Fatty Acids.
AB  - Developing endosperms and embryos accumulating triacylglycerols rich in caproyl
      (decanoyl) groups (i.e. developing embryos of Cuphea procumbens and Ulmus glabra)
      had microsomal acyl hydrolases with high selectivities toward phosphatidylcholine
      with this acyl group. Similarly, membranes from Euphorbia lagascae and Ricinus
      communis endosperms, which accumulate triacylglycerols with vernoleate (12-epoxy
      octadeca-9-enoate) and ricinoleate (12-hydroxy-octadeca-9-enoate), respectively,
      had acyl hydrolases that selectively removed their respective oxygenated acyl
      group from the phospholipids. The activities toward phospholipid substrates with
      epoxy, hydroxy, and medium-chain acyl groups varied greatly between microsomal
      preparations from different plant species. Epoxidated and hydroxylated acyl
      groups in sn-1 and sn-2 positions of phosphatidylcholine and in sn-1
      lysophosphatidylcholine were hydrolyzed to a similar extent, whereas the
      hydrolysis of caproyl groups was highly dependent on the positional localization.

PMID- 12228416
TI  - Cellulose-Lignin Interactions (A Computational Study).
AB  - Within a broader program of study of the molecular structure of plant cell walls,
      molecular dynamics calculations were used to explore the character of the motion
      of lignin model compounds near a cellulose surface. Model cellulose microfibrils,
      which have a large number of hydroxyl groups on the surface, appear to have a net
      attractive interaction with the lignin models examined in this study. The lignin
      monomer coniferyl alcohol rapidly adsorbed onto the surface from a water layer
      after it was released 13 A from the surface. The major long-range force
      responsible for this adsorption is likely electrostatic. The attractive
      interaction is sufficient to restrict the motion of coniferyl alcohol when it is
      within 1 A of the surface and to orient the phenyl ring parallel to the surface.
      The [beta]-O-4-linked trimer also was observed to adsorb onto the surface with
      two of its phenyl rings parallel to the surface. These results suggest a
      mechanism by which the polysaccharide component of the plant cell wall could
      influence the structure of lignin. Furthermore, they provide a rationalization of
      the experimental observation that polysaccharides can change the course of
      dehydrogenation polymerization of cinnamyl alcohols.

PMID- 12228417
TI  - A New Pressure Probe Method to Determine the Average Volumetric Elastic Modulus
      of Cells in Plant Tissue.
AB  - A new in vivo method was used to determine an average volumetric elastic modulus
      ([epsilon]ave) for nongrowing cells in plant tissue. This method requires that
      both the relative transpiration rate, T, of the tissue and the average turgor
      pressure decay rate, (dP/dt)ave, of the cells are measured after the water source
      is removed from the plant tissue. Then [epsilon]ave is calculated from the
      equation [epsilon]ave = (-dP/dt)ave/T. This method was used to determine
      [epsilon]ave for cortical cells in stems of pea seedlings (Pisum sativum L.). The
      results demonstrate that [epsilon]ave increases from virtually zero at low P
      (approximately 0.01MPa) to approximately 10 MPa at high P (approximately 0.5
      MPa). Analyses of the results indicate that the relationship between [epsilon]ave
      and P can be approximated by a linear function and more accurately approximated
      by a saturating exponential function: [epsilon]ave = [epsilon][infinity symbol][1
      - exp {-k(P - Po)}], where Po is a plateau pressure (approximately 0.01 MPa), k
      is a rate constant (approximately 7 per MPa), and [epsilon][infinity symbol]
      (approximately 10 MPa) is the hypothetical maximum value of [epsilon]ave as P ->
      [infinity symbol]. Solutions for the turgor pressure decay (due to transpiration)
      as functions of time and symplasmic water mass (after the water source is
      removed) are derived.

PMID- 12228418
TI  - Dissection of Oxidative Stress Tolerance Using Transgenic Plants.

PMID- 12228419
TI  - Tissue-Specific Expression of Germin-Like Oxalate Oxidase during Development and
      Fungal Infection of Barley Seedlings.
AB  - Oxalate oxidase activity was detected in situ during the development of barley
      seedlings. The presence of germin-like oxalate oxidase was confirmed by
      immunoblotting using an antibody directed against wheat germin produced in
      Escherichia coli, which is shown to cross-react with barley (Hordeum vulgare)
      oxalate oxidase and by enzymatic assay after electrophoresis of the protein
      extracts on polyacrylamide gels. In 3-d-old barley seedlings, oxalate oxidase is
      localized in the epidermal cells of the mature region of primary roots and in the
      coleorhiza. After 10 d of growth, the activity is detectable only in the
      coleorhiza. Moreover, we show that oxalate oxidase is induced in barley leaves
      during infection by the fungus Erysiphe graminis f. sp. hordei but not by
      wounding. Thus, oxalate oxidase is a new class of proteins that responds to
      pathogen attack. We propose that oxalate oxidase could have a role in plant
      defense through the production of H2O2.

PMID- 12228420
TI  - Cell-Wall Proteins Induced by Water Deficit in Bean (Phaseolus vulgaris L.)
      Seedlings.
AB  - In the last few years, much attention has been given to the role of proteins that
      accumulate during water deficit. In this work, we analyzed the electrophoretic
      patterns of basic protein extracts, enriched for a number of cell-wall proteins,
      from bean (Phaseolus vulgaris L.) seedlings and 21-d-old plants subjected to
      water deficit. Three major basic proteins accumulated in bean seedlings exposed
      to low water potentials, with apparent molecular masses of 36, 33, and 22 kD,
      which we refer to as p36, p33, and p22, respectively. Leaves and roots of 21-d
      old plants grown under low-water-availability conditions accumulated only p36 and
      p33 proteins. In 21-d-old plants subjected to a fast rate of water loss, both p33
      and p36 accumulated to approximately the same levels, whereas if the plants were
      subjected to a gradual loss of water, p33 accumulated to higher levels. Both p36
      and p33 were glycosylated and were found in the cell-wall fraction. In contrast,
      p22 was not glycosylated and was found in the soluble fraction. The accumulation
      of these proteins was also induced by abscisic acid (0.1-1.0 mM) treatment but
      not by wounding or by jasmonate treatment.

PMID- 12228421
TI  - 2,4-Dichlorophenoxyacetic Acid and Related Chlorinated Compounds Inhibit Two
      Auxin-Regulated Type-III Tobacco Glutathione S-Transferases.
AB  - Two auxin-inducible glutathione S-transferase (GST, EC 2.5.1.18) isozymes from
      tobacco (Nicotiana tabacum, White Burley) were partially characterized. GST1-1
      and GST2-1 are members of a recently identified new type of plant GST isozymes
      that we will here refer to as type III. Both enzymes were active, with 1-chloro
      2,4-dinitrobenzene as a substrate, when expressed in bacteria as fusion proteins.
      The apparent Km for 1-chloro-2,4-dinitrobenzene was found to be 0.85 [plus or
      minus] 0.25 mM for GST1-1 and 0.20 [plus or minus] 0.15 mM for GST2-1. The
      apparent Km for glutathione was similar for both enzymes, 0.40 [plus or minus]
      0.15 mM. The in vitro activity of both enzymes could be inhibited by the
      synthetic auxin 2,4-dichlorophenoxyacetic acid, with an apparent Ki of 80 [plus
      or minus] 40 [mu]M for GST1-1 and 200 [plus or minus] 100 [mu]M for GST2-1. The
      GST1-1 was also inhibited by structurally related substances, such as 2,4
      dichlorobenzoic acid, with a roughly similar Ki. The nonchlorinated structures
      benzoic acid and phenoxyacetic acid did not inhibit. p-Chloroisobutyric acid, or
      clofibric acid, an auxin-transport inhibitor, was found to be an active inhibitor
      as well. The strongest inhibitor identified, however, was a phenylacetic acid
      derivative, ethacrynic acid, which showed an apparent Ki of 5 [plus or minus] 5
      [mu]M for both enzymes. This substance is a known inducer as well as a substrate
      of specific mammalian GSTs. The results presented here indicate that the type III
      plant GSTs might be involved in the metabolism or transport of chlorinated
      substances that are structurally related to auxins. The possibility that auxins
      are endogenous ligands or substrates for GSTs is discussed.

PMID- 12228422
TI  - Biogenesis and Ultrastructure of Carboxysomes from Wild Type and Mutants of
      Synechococcus sp. Strain PCC 7942.
AB  - Immature inclusions representing three progressive steps of carboxysome
      biogenesis have been identified in Synechococcus during the period of adaptation
      to low-CO2 conditions: (a) ring-shaped structures, (b) electron-translucent
      inclusions with the shape of a carboxysome and the internal orderly arrangement
      of ribulose-1,5-bisphosphate carboxylase oxygenase (Rubisco) molecules, and (c)
      carboxysomes with an internal electron-translucent area, which seem to be the
      penultimate stage of carboxysome maturation. The ability to build up normal
      carboxysomes is impaired in three (M3, EK6, and D4) of four high-carbon-requiring
      mutants studied in this work. M3 and EK6 exhibit abundant immature electron
      translucent carboxysomes but no mature ones. This finding supports the contention
      that an open reading frame located 7.5 kb upstream of the gene encoding the large
      subunit of Rubisco (altered in M3) is involved in the carboxysome composition and
      confirms the structural role of the small subunit of Rubisco (slightly modified
      in EK6) in the assembly of these structures. D4 shows few typical carboxysomes
      and frequent immature types, its genetic lesion affecting the apparently
      unrelated gene encoding a subunit of phosphoribosyl aminoamidazole carboxylase of
      the purine biosynthesis pathway. Revertants EK20 (EK6) and RK13 (D4) have normal
      carboxysomes, which means that the restoration of the ability to grow under low
      CO2 coincides with the proper assembling of these structures. N5, a transport
      mutant due to the alteration of the gene encoding subunit 2 of NADH
      dehydrogenase, shows an increase in the number and size of carboxysomes and
      frequent bar-shaped ones.

PMID- 12228423
TI  - Regulation of Early Light-Inducible Protein Gene Expression by Blue and Red Light
      in Etiolated Seedlings Involves Nuclear and Plastid Factors.
AB  - Early light-inducible proteins (ELIPs) are nuclear-encoded chloroplast proteins
      whose genes are transiently transcribed during the greening process of etiolated
      plants. In the present work the regulation of ELIP gene expression by blue and
      red light has been investigated in plumulas of etiolated pea plants (Pisum
      sativum). The results show that the steady-state level of ELIP transcripts is
      controlled by a combined action of phytochrome and blue light receptor systems
      and, in addition, depends on the age of the seedlings. Both a low-light fluence
      system of blue and a very-low-fluence system of red light are involved in ELIP
      induction. The threshold for accumulation of ELIP transcripts was as low as 10-5
      [mu]E m-2 s-1 for both light qualities but a different pattern of accumulation
      was obtained in blue and in red light. Blue light not only acts at the level of
      transcription but also regulates the stability of the ELIP transcripts in a light
      intensity-dependent manner. Moreover, it is shown that product(s) of nuclear
      gene(s) negatively regulate the steady-state level of ELIP transcripts during the
      1st h of illumination with red light. Preillumination of seedlings with white
      light abolishes this repression. Accumulation of ELIP transcripts requires
      "plastid factors" in both blue and red light qualities.

PMID- 12228424
TI  - Fatty Acid Desaturation during Chilling Acclimation Is One of the Factors
      Involved in Conferring Low-Temperature Tolerance to Young Tobacco Leaves.
AB  - The FAD7 gene, a gene for a chloroplast [omega]-3 fatty acid desaturase, is
      responsible for the trienoic fatty acid (TA) formation in leaf tissues. The TA
      content of the leaf tissue of the 25[deg]C-grown transgenic tobacco (Nicotiana
      tabacum cv SR1) plants, in which the FAD7 gene from Arabidopsis thaliana was
      overexpressed, increased uniformly by about 10%. Fatty acid unsaturation in all
      major leaf polar lipid species increased in the 25[deg]C-grown FAD7 transformants
      but was approximately the same between the control plants and the FAD7
      transformants when grown at 15[deg]C. Therefore, the overexpression of the
      exogenous FAD7 gene leads to the same consequence in the tobacco plants as the
      low-temperature-induced TA production that may be catalyzed by an endogenous,
      temperature-regulated chloroplast [omega]-3 fatty acid desaturase. In the
      25[deg]C-grown control plants, the chilling treatment caused symptoms of leaf
      chlorosis and suppression of leaf growth. The 25[deg]C-grown FAD7 transgenic
      plants conferred alleviation of these chilling-induced symptoms. A reductions of
      the chilling injury similar to that of the FAD7 transformants was also observed
      in the 15[deg]C-preincubated control plants. These results indicate that the
      increased TA production during chilling acclimation is one of the prerequisites
      for the normal leaf development at low, nonfreezing temperatures.

PMID- 12228425
TI  - Drought Stress, Permeability to O2 Diffusion, and the Respiratory Kinetics of
      Soybean Root Nodules.
AB  - In legume nodules, treatments such as detopping or nitrate fertilization inhibit
      nodule metabolism and N2 fixation by decreasing the nodule's permeability to O2
      diffusion, thereby decreasing the infected cell O2 concentration (Oi) and
      increasing the degree to which nodule metabolism is limited by O2 availability.
      In the present study we used nodule oximetry to assess and compare the role of O2
      limitation in soybean (Glycine max L. Merr) nodules inhibited by either drought
      or detopping. Compared to detopping, drought caused only minor decreases in Oi,
      and when the external O2 concentration was increased to raise Oi, the infected
      cell respiration rate in the drought-stressed plants was not stimulated as much
      as it was in the nodules of the detopped plants. Unlike those in detopped plants,
      nodules exposed to moderate drought stress displayed an O2-sufficient respiration
      rate that was significantly lower than that in control nodules. Despite possible
      side effects of oximetry in altering nodule metabolism, these results provided
      direct evidence that, compared to detopping, O2 limitation plays a minor role in
      the inhibition of nodule metabolism during drought stress and changes in nodule
      permeability are the effect, not the cause, of a drought-induced inhibition of
      nodule metabolism and the O2-suffiecient rate of respiration.

PMID- 12228426
TI  - Metabolic Implications in the Biochemical Responses to Iron Deficiency in
      Cucumber (Cucumis sativus L.) Roots.
AB  - Strategy I plants respond to Fe deficiency by inducing morphological and
      biochemical modifications at the root level that are apt to make iron available
      for uptake. Cucumber (Cucumis sativus L.) grown in the absence of Fe has been
      shown to increase the capacity to acidify the rhizosphere and Fe3+ reduction
      activity. We have determined in these roots some metabolic activities that might
      be correlated with the increased proton extrusion. Proton efflux from roots may
      be followed by a mechanism regulating the cytosolic pH according to the pH-stat
      theory. Roots grown in the absence of Fe showed an increase in dark 14CO2
      fixation and organic acid synthesis and a 6-fold increase in the extractable
      phosphoenolpyruvate carboxylase activity with respect to the control roots.
      Dehydrogenase activities producing cytosolic NAD(P)H were also increased under Fe
      deficiency. The presence of Fe2+, but not Fe3+, inhibited dark 14CO2 fixation in
      a range between 24 and 52% but did not show any effect on the in vitro
      phosphoenolpyruvate carboxylase activity.

PMID- 12228427
TI  - Effects of Temperature on Infected Cell O2 Concentration and Adenylate Levels in
      Attached Soybean Nodules.
AB  - To assess the role of O2 in the regulation of nodule metabolism following a
      decrease or an increase in temperature, the fractional oxygenation of
      leghemoglobin (FOL) was measured in soybean (Glycine max L. Merr.) nodules during
      rapid and gradual changes in temperature from 20[deg]C to either 15 or 25[deg]C.
      The affinity of leghemoglobin for O2 was also measured at each temperature and
      the values were used to calculate the infected cell O2 concentration (Oi). After
      nodules were transferred to 15[deg]C, FOL and Oi increased and adenylate energy
      charge (AEC = [ATP + 0.5ADP]/[ATP + ADP + AMP]) increased from 0.70 to 0.78. The
      temperature increase was associated with a decrease in FOL and Oi. We concluded
      that changes in nodule temperature alter the respiratory demand of the nodules
      for O2, resulting in a change in Oi and a shift in the balance between ATP
      consumption and ATP production within the nodule tissue.

PMID- 12228428
TI  - Regulation of Nitrate Reductase during Early Seedling Growth (A Role for
      Asparagine and Glutamine).
AB  - Growth systems that either permit (wet system) or prevent (dry system) the
      hydrolysis of endosperm reserves in maize (Zea mays) seedlings were developed to
      study the effect of endosperm reserves on the acquisition of external nitrogen.
      Three-day-old seedlings treated with 5 mM KNO3 for 24 h had higher levels of
      nitrate reductase (NR) activity and protein in shoot and root tissues in the dry
      relative to the wet system. This suggests that the induction of NR is sensitive
      to products of hydrolysis of endosperm reserves. Asparagine (1 mM) or glutamine
      (1 mM), potential products of that hydrolysis, inhibited the induction of NADH
      dependent root NR in the dry system by about 70%. The inhibition of the induction
      of NR activity in the wet system was only about 35%, suggesting that the enzyme
      in the wet system was already partially repressed at 3 d. At 5 d, when asparagine
      and glutamine levels in the plant tissue had decreased, the induction of root NR
      activity was inhibited to a similar extent in the two growth systems by amide
      additions. The shoot enzyme was less sensitive to amide additions, and 10 mM
      concentrations of either amide was required for a 65% inhibition.

PMID- 12228429
TI  - Bean [alpha]-Amylase Inhibitor Confers Resistance to the Pea Weevil (Bruchus
      pisorum) in Transgenic Peas (Pisum sativum L.).
AB  - Bruchid larvae cause major losses of grain legume crops through-out the world.
      Some bruchid species, such as the cowpea weevil and the azuki bean weevil, are
      pests that damage stored seeds. Others, such as the pea weevil (Bruchus pisorum),
      attack the crop growing in the field. We transferred the cDNA encoding the
      [alpha]-amylase inhibitor ([alpha]-AI) found in the seeds of the common bean
      (Phaseolus vulgaris) into pea (Pisum sativum) using Agrobacterium-mediated
      transformation. Expression was driven by the promoter of phytohemagglutinin,
      another bean seed protein. The [alpha]-amylase inhibitor gene was stably
      expressed in the transgenic pea seeds at least to the T5 seed generation, and
      [alpha]-AI accumulated in the seeds up to 3% of soluble protein. This level is
      somewhat higher than that normally found in beans, which contain 1 to 2% [alpha]
      AI. In the T5 seed generation the development of pea weevil larvae was blocked at
      an early stage. Seed damage was minimal and seed yield was not significantly
      reduced in the transgenic plants. These results confirm the feasibility of
      protecting other grain legumes such as lentils, mungbean, groundnuts, and
      chickpeas against a variety of bruchids using the same approach. Although [alpha]
      AI also inhibits human [alpha]-amylase, cooked peas should not have a negative
      impact on human energy metabolism.

PMID- 12228430
TI  - Plasma Membrane Redox Enzyme Is Involved in the Synthesis of O2- and H2O2 by
      Phytophthora Elicitor-Stimulated Rose Cells.
AB  - An elicitor prepared from the autoclaved cell walls of Phytophthora sp. induced
      O2- generation and H2O2 accumulation by cultured cells of Rosa damascena Mill. cv
      Gloire de Guilan. N,N-Diethyldithiocarbamate, a superoxide dismutase inhibitior,
      blocked H2O2 accumulation and caused a dramatic accumulation of O2- by elicitor
      treated rose cells. In the absence of N,N-diethyldithiocarbamate no detectable O2
      was accumulated. Diphenyleneiodonium, quinacrine, pyridine, and imidazole,
      inhibitors of the mammalian neutrophil NADPH oxidase responsible for the
      generation of O2- during phagocytosis, inhibited O2- generation by elicitor
      treated rose cells. Diphenyleneiodonium also inhibited NADH-dependent O2-
      production by plasma membranes isolated from rose cells. None of the four
      compounds inhibited the peroxidase activity in the cell-suspension medium. These
      results demonstrate that elicitor-stimulated accumulation of H2O2 comes only from
      superoxide dismutase-catalyzed dismutation of O2-. The data are inconsistent with
      the hypothesis that the synthesis of O2- is catalyzed by extracellular peroxidase
      and suggest that the enzyme responsible for the synthesis of O2- by elicitor
      treated rose cells might be similar to the mammalian neutrophil NADPH oxidase.

PMID- 12228431
TI  - Sucrose:Fructan 6-Fructosyltransferase, a Key Enzyme for Diverting Carbon from
      Sucrose to Fructan in Barley Leaves.
AB  - Sucrose:sucrose 6-fructosyltransferase, an enzyme activity recently identified in
      fructan-accumulating barley (Hordeum vulgare) leaves, was further characterized.
      The purified enzyme catalyzed the transfer of a fructosyl group from sucrose to
      various acceptors. It displayed some [beta]-fructosidase (invertase) activity,
      indicating that water could act as fructosyl acceptor. Moreover, it transferred
      the fructosyl residue of unlabeled sucrose to [U-14C]Glc, producing [U
      14C]sucrose and unlabeled glucose. Most significantly for fructan synthesis, the
      enzyme used as acceptors but not as donors a variety of oligofructans containing
      [beta](2->1)- and [beta](2->6)-linked fructosyl moieties. Thus, it acted as a
      general sucrose:fructan fructosyltransferase. The products formed by the enzyme
      from sucrose and various purified, structurally characterized oligofructans were
      analyzed by liquid chromatography and identified by comparison with structurally
      characterized standards. The results showed that the enzyme formed exclusively
      [beta](2->6) fructosyl-fructose linkages, either initiating or elongating a
      fructan chain of the phlein type. We propose, therefore, to rename the purified
      enzyme sucrose:fructan 6-fructosyltransferase.

PMID- 12228432
TI  - Magnesium Adenosine 5[prime]-Triphosphate-Energized Transport of Glutathione-S
      Conjugates by Plant Vacuolar Membrane Vesicles.
AB  - By characterization of the uptake of glutathione-S-conjugates, principally
      dinitrophenyl-S-glutathione (DNP-GS), by vacuolar membrane vesicles, we
      demonstrate that a subset of energy-dependent transport processes in plants are
      not H+-coupled but instead are directly energized by MgATP. The most salient
      features of this transport pathway are: (a) its specific, obligate requirement
      for MgATP as energy source; (b) the necessity for hydrolysis of the [gamma]
      phosphate of MgATP for uptake; (c) the insensitivity of uptake to uncouplers of
      the transtonoplast H+ gradient (carbonylcyanide 4
      trifluoromethoxyphenylhydrazone, gramicidin-D, and NH4Cl); (d) its pronounced
      sensitivity to vanadate and partial inhibition by vinblastine and verapamil; (e)
      the lack of chemical modification of DNP-GS either during or after transport; (f)
      the capacity of S-conjugates of chloroacetanilide herbicides, such as metolachlor
      GS, but not free herbicide, to inhibit uptake; and (g) the ability of vacuolar
      membrane vesicles purified from a broad range of plant species, including
      Arabidopsis, Beta, Vigna, and Zea, to mediate MgATP-dependent, H+-electrochemical
      potential difference-independent DNP-GS uptake. On the basis of these findings it
      is proposed that the transport of DNP-GS across the vacuolar membrane of plant
      cells is catalyzed by a glutathione-conjugate transporter that directly employs
      MgATP rather than the energy contained in the transtonoplast H+-electrochemical
      potential difference to drive uptake. The broad distribution of the vacuolar DNP
      GS transporter and its inhibition by metolachlor-GS are consistent with the
      notion that it plays a general role in the vacuolar sequestration of glutathione
      conjugable cytotoxic agents.

PMID- 12228433
TI  - The Resistance of the Diffusion Barrier in Nodules of Myrica gale L. Changes in
      Response to Temperature but Not to Partial Pressure of O2.
AB  - Rates of C2H2 reduction and CO2 evolution by nodules were measured in a
      flowthrough system using intact plants of Myrica gale L. Both activities
      increased linearly with increasing partial pressure of O2 (pO2) up to 18 kPa. The
      linear relationship between CO2 evolution and pO2 at pO2 values between 6 and 18
      kPa suggests that the diffusion barrier has a constant resistance. The lack of a
      variable resistance was further supported by sustained increases and decreases in
      nodule activities in response to changes in pO2 in the range of 6 to 20 kPa O2.
      When pO2 was increased above 20 kPa, C2H2 reduction and CO2 evolution continually
      declined with time. These results confirm that the diffusion barrier in nodules
      of M. gale is not variable in response to changes in pO2. The effect of
      temperature was examined at 8 and 20 kPa O2. Rates of C2H2 reduction and CO2
      evolution increased with increasing temperature from 10 to 30[deg]C at both pO2
      values. These results indicate that the diffusion resistance of the barrier
      changes as temperature changes, with the resistance decreasing as temperature
      increases.

PMID- 12228434
TI  - Accuracy of Deoxynucleotide Incorporation by Soybean Chloroplast DNA Polymerases
      Is Independent of the Presence of a 3[prime] to 5[prime] Exonuclease.
AB  - DNA polymerase was purified from soybean (Glycine max) chloroplasts that were
      actively replicating DNA. The main form (form I) of the enzyme was associated
      with a low level of 3[prime] to 5[prime] exonuclease activity throughout
      purification, although the ratio of exonuclease to polymerase activity decreased
      with each successive purification step. A second form (form II) of DNA
      polymerase, which elutes from DEAE-cellulose at a higher salt concentration than
      form I, was devoid of any exonuclease activity. To assess the potential function
      of the 3[prime] to 5[prime] exonuclease in proofreading, the fidelity of
      deoxynucleotide incorporation was measured for form I DNA polymerase throughout
      purification. Despite the steadily decreasing ratio of 3[prime] to 5[prime]
      exonuclease to polymerase activity, the extent of misincorporation by form I
      enzyme remained unchanged during the final purification steps, suggesting that
      the exonuclease did not contribute to the accuracy of DNA synthesis by this
      polymerase. Fidelity of form I DNA polymerase, when compared with that of form
      II, revealed a higher level of misincorporation for form I enzyme, a finding that
      is consistent with the exonuclease playing little or no role in exonucleolytic
      proofreading.

PMID- 12228435
TI  - Selective Inhibition of Auxin-Stimulated NADH Oxidase Activity and Elongation
      Growth of Soybean Hypocotyls by Thiol Reagents.
AB  - The NADH oxidase activity of isolated vesicles of soybean (Glycine max cv
      Williams 82) plasma membranes and elongation growth of 1-cm-long hypocotyl
      segments were stimulated by auxins (indole-3-acetic acid or 2,4
      dichlorophenoxyacetic acid [2,4-D]). The auxin-induced stimulations of both NADH
      oxidase and growth were prevented by the thiol reagents N-ethylmaleimide, p
      chloromercuribenzoate, 5,5[prime]-dithiobis(2-nitrophenylbenzoic acid),
      dithiothreitol, and reduced glutathione. These same reagents largely were without
      effect on or stimulated slightly the basal levels of NADH oxidase and growth when
      assayed in the absence of auxins. In the presence of dithiothreitol or reduced
      glutathione, both 2,4-D and indole-3-acetic acid either failed to stimulate or
      inhibited the NADH oxidase activity. The rapidity of the response at a given
      concentration of thiol reagent and the degree of inhibition of the 2,4-D-induced
      NADH oxidase activity were dependent on order of reagent addition. If the thiol
      reagents were added first, auxin stimulations were prevented. If auxins were
      added first, the inhibitions by the thiol reagents were delayed or higher
      concentrations of thiol reagents were required to achieve inhibition. The results
      demonstrate a fundamental difference between the auxin-stimulated and the
      constitutive NADH oxidase activities of soybean plasma membranes that suggest an
      involvement of active-site thiols in the auxin-stimulated but not in the
      constitutive activity.

PMID- 12228436
TI  - MgATP-Dependent Transport of Phytochelatins Across the Tonoplast of Oat Roots.
AB  - In Cd-exposed oat (Avena sativa) roots Cd was found to be associated primarily
      with the phytochelatin ([gamma]-glutamylcysteinyl)3-glutamic acid
      [([gamma]EC)3G], with a peptide to Cd ratio of 1:3 (cysteine to Cd ratio of 1:1),
      even though both ([gamma]EC)2G and ([gamma]EC)3G were present in the roots.
      Phytochelatins are known to accumulate in the vacuoles of plant cells on exposure
      to Cd, but the mechanism is not clear. Here we present evidence for the transport
      of the phytochelatins ([gamma]EC)3G and ([gamma]EC)2G as well as the Cd complex
      Cd-([gamma]EC)3G across the tonoplast of oat roots. Transport of ([gamma]EC)3G
      had a Km, for MgATP of 0.18 mM and a Vmax of 0.7 to 1 nmol mg-1 protein min-1.
      Transport of ([gamma]EC)3G was also energized by MgGTP and to a lesser extent
      MgUTP and was highly sensitive to orthovanadate, with a 50%-inhibitory
      concentration of 0.9 [mu]M. The Cd complex Cd-([gamma]EC)3G and ([gamma]EC)2G
      were also transported in a MgATP-dependent, vanadate-sensitive manner. Therefore,
      this process is a candidate for the transport of both phytochelatins, and Cd as
      its peptide complex, from the cytoplasm into the vacuole.

PMID- 12228437
TI  - Expression of NADH-Specific and NAD(P)H-Bispecific Nitrate Reductase Genes in
      Response to Nitrate in Barley.
AB  - Barley (Hordeum vulgare L.) has two, differentially regulated, nitrate reductase
      (NR) genes, one encoding the NADH-specific NR (Nar1) and the other encoding the
      NAD(P)H-bispecific NR (Nar7). Regulation of the two NR genes by nitrate was
      investigated in wild-type Steptoe and in an NADH-specific NR structural gene
      mutant (Az12). Gene-specific probes were used to estimate NADH and NAD(P)H NR
      mRNAs. The kinetics of induction by nitrate were similar for the two NR genes;
      expression was generally below the limits of detection prior to induction,
      reached maximum levels after 1 to 2 h of induction in roots and 4 to 8 h of
      induction in leaves, and then declined to steady-state levels. Derepression of
      the NAD(P)H NR gene in leaves of the NADH-specific NR gene mutant Az12 did not
      appear to be associated with changes in nitrate assimilation products or nitrate
      flux. Nitrate deprivation resulted in rapid decreases in NADH and NAD(P)H NR
      mRNAs in seedling roots and leaves and equally rapid decreases in the
      concentration of nitrate in the xylem sap. These results indicate that factors
      affecting nitrate uptake and transport could have a direct influence on NR
      expression in barley leaves.

PMID- 12228438
TI  - Leaf Phosphate Status, Photosynthesis, and Carbon Partitioning in Sugar Beet (IV.
      Changes with Time Following Increased Supply of Phosphate to Low-Phosphate
      Plants).
AB  - Changes in photosynthesis, carbon partitioning, and growth following resupply of
      orthophosphate (Pi) to moderately P-deficient plants (low-P) were determined for
      sugar beets (Beta vulgaris L. cv F58-554H1) cultured hydroponically in growth
      chambers. One set of plants was supplied with 1.0 mM Pi in half-strength Hoagland
      solution (control plants), and a second set (low-P plants) was supplied with 0.05
      mM Pi. At the end of 2 weeks, the low-P plants were resupplied with 1.0 mM Pi.
      Low-P plants rapidly accumulated large amounts of Pi, and the photosynthesis rate
      increased to control values within 4 to 6 h. The rate of photosynthesis appeared
      to be controlled by ribulose-1,5-bisphosphate (RuBP); low P reduced
      photosynthesis and RuBP levels, and P resupply increased photosynthesis and RuBP
      in a manner parallel with time. Low-P treatment reduced adenylate levels
      substantially but not nicotinamide nucleotides; adenylate levels recovered to
      control values over 3 to 6 h. With low P, more photosynthate is allocated to non
      P carbon compounds (e.g. starch, sucrose) than to sugar phosphates. When P is
      resupplied, sugar phosphates increase as starch and sucrose pools decrease; this
      increase in leaf (chloroplast) sugar phosphates was most likely responsible for
      the increases in RuBP and photosynthesis and may have increased adenylate levels
      (through enhanced levels of ribose-5-phosphate).

PMID- 12228439
TI  - Nitrate Effects on Nodule Oxygen Permeability and Leghemoglobin (Nodule Oximetry
      and Computer Modeling).
AB  - Two current hypotheses to explain nitrate inhibition of nodule function both
      involve decreased O2 supply for respiration in support of N2 fixation. This
      decrease could result from either (a) decreased O2 permeability (PO) of the
      nodule cortex, or (b) conversion of leghemoglobin (Lb) to an inactive, nitrosyl
      form. These hypotheses were tested using alfalfa (Medicago sativa L. cv
      Weevlchek) and birdsfoot trefoil (Lotus corniculatus L. cv Fergus) plants grown
      in growth pouches under controlled conditions. Nodulated roots were exposed to 10
      mM KNO3 or KCI. Fractional oxygenation of Lb under air (FOLair), relative
      concentration of functional Lb, apparent PO, and O2-saturated central zone
      respiration rate were all monitored by nodule oximetry. Apparent PO and FOLair in
      nitrate-treated nodules decreased to <50% of values for KCI controls within 24 h,
      but there was no decrease in functional Lb concentration during the first 72 h.
      In nitrate-treated alfalfa, but not in birdsfoot trefoil, FOLair, apparent PO,
      and O2-saturated central zone respiration rate decreased during each light period
      and recovered somewhat during the subsequent dark period. This species difference
      could be explained by greater reliance on photoreduction of nitrate in alfalfa
      than in birdsfoot trefoil. Computer simulations extended the experimental
      results, showing that previously reported decreases in apparent PO of Glycine max
      nodules with nitrate exposure cannot be explained by hypothetical decreases in
      the concentration or O2 affinity of Lb.

PMID- 12228440
TI  - Seed Dormancy in Red Rice (Oryza sativa) (IX. Embryo Fructose-2,6-Bisphosphate
      during Dormancy Breaking and Subsequent Germination).
AB  - Fructose-2,6-bisphosphate (Fru-2,6-bisP) was evaluated as a potential marker for
      the dormancy-breaking phase or the germination phase before pericarp splitting in
      red rice (Oryza sativa). During 4 h of imbibition at 30[deg]C, Fru-2,6-bisP of
      dehulled dormant and nondormant seeds increased to 0.26 and 0.38 pmol embryo-1,
      respectively. In nondormant seeds, embryo Fru-2,6-bisP content remained stable
      until the onset of pericarp splitting (12 h) and increased rapidly thereafter. In
      dormant seeds, Fru-2,6-bisP declined to 0.09 pmol embryo-1 at 24 h. Embryo Fru
      2,6-bisP was correlated with O2 uptake of dormant and nondormant seeds. A 24-h
      exposure of dehulled, water-imbibed, dormant seeds to treatments yielding >90%
      germination (sodium nitrite [4 mM], propionic acid [22 mM], methyl propionate [32
      mM], propanol [75 mM], and propionaldehyde [40 mM]) led to changes in embryo Fru
      2,6-bisP that were unrelated to the final germination percentages. Furthermore, a
      2-h pulse of propionaldehyde increased Fru-2,6-bisP 4-fold but did not break
      dormancy. Whereas nitrite and propionaldehyde increased Fru-2,6-bisP to 0.33 pmol
      embryo-1 after 2 h of contact, propionic acid and methyl propionate did not
      increase Fru-2,6-bisP above the untreated control. In all cases, further
      increases in Fru-2,6-bisP occurred after pericarp splitting. However, the plateau
      Fru-2,6-bisP attained during chemical contact was inversely correlated with
      elapsed time to 30% germination (r = -0.978). Therefore, although Fru-2,6-bisP is
      not a universal marker for dormancy release, its rapid increase during nitrite
      and propionaldehyde treatments suggests that events associated with dormancy
      breaking can occur within 2 h of chemical treatment.

PMID- 12228441
TI  - Investigation of Local Ethylene Emission from Intact Cherry Tomatoes by Means of
      Photothermal Deflection and Photoacoustic Detection.
AB  - The function of the coronet region of the cherry tomato (Lycopersicon esculentum
      Cherry) as the main emission channel for ethylene was investigated. Ethylene was
      measured employing two laser-based detection systems, the photothermal deflection
      instrument and the photoacoustic detection setup. It is possible to detect
      minimum ethylene concentrations of 1 nL L-1 locally and rapidly with the first
      instrument and concentrations of 6 pL L-1 in a continuous flow system with the
      second setup. The continuous flow system makes it possible to change the air
      composition and to monitor its influence on the ethylene production of the
      tomato. The response times of the two instruments are 30 s and 4 min,
      respectively. The local character of the measurements makes it possible to
      determine the emission sites of the gaseous plant hormone ethylene and their
      relative importance. Transient anoxic conditions stop production of ethylene;
      return to aerobic conditions shows the evolution of the accumulated ethylene
      precursor 1-aminocyclopropane-1-carboxylic acid and its renewed production on the
      measured ethylene emission, with a time resolution of several minutes.
      Temporarily sealing the main emission channel yields results comparable to
      anoxia.

PMID- 12228442
TI  - Computer-Assisted Identification of Protoplasts Responsible for Rare Division
      Events Reveals Guard-Cell Totipotency.
AB  - With the use of a computer-controlled microscope system to assist in the
      positioning and rapid relocation of large numbers of cultured cells, we were able
      to identify those protoplasts with the capacity to divide within a highly
      recalcitrant culture in which only a tiny fraction of the total population
      proceeds to produce viable microcalli. In the cultures used, comprising Beta
      vulgaris L. (sugar beet) leaf protoplasts, it was confirmed that these cells can
      be recognized solely on the basis of morphological characters. Therefore, a
      direct link exists between competence for cell division in vitro and cell type.
      Divergent callus morphologies and totipotent potential could also be ascribed to
      distinct protoplast types and hence to cells with a specific origin. The
      progenitors of the totipotent protoplasts in these cultures have been confirmed
      as being stomatal guard cells. Consequently, in plants even the most highly
      adapted living cells clearly retain and can reactivate all of the functional
      genetic information necessary to recreate the whole organism; an extreme degree
      of cytodifferentiation is, therefore, no hindrance to expressing totipotent
      potential. In addition to the considerable practical value of these findings,
      their implications concerning our understanding of both the control of gene
      expression and plant cell differentiation and its reversibility are of
      fundamental significance.

PMID- 12228443
TI  - In Situ Association of Calvin Cycle Enzymes, Ribulose-1,5-Bisphosphate
      Carboxylase/Oxygenase Activase, Ferredoxin-NADP+ Reductase, and Nitrite Reductase
      with Thylakoid and Pyrenoid Membranes of Chlamydomonas reinhardtii Chloroplasts
      as Revealed by Immunoelectron Microscopy.
AB  - The in situ localization of the chloroplast enzymes ribulose-1,5-bisphosphate
      carboxylase (Rubisco), Rubisco activase, ribose-5-phosphate isomerase,
      glyceraldehyde-3-phosphate dehydrogenase, aldolase, nitrite reductase, ferredoxin
      NADP+ reductase, and H+-ATP synthase was studied by immunoelectron microscopy in
      Chlamydomonas reinhardtii. Immunogold labeling revealed that, despite Rubisco in
      the pyrenoid matrix, Calvin cycle enzymes, Rubisco activase, nitrite reductase,
      ferredoxin-NADP+ reductase, and H+-ATP synthase are associated predominantly with
      chloroplast thylakoid membranes and the inner surface of the pyrenoid membrane.
      This is in accord with previous enzyme localization studies in higher plants
      (K.H. Suss, C. Arkona, R. Manteuffel, K. Adler [1993] Proc Natl Acad Sci USA 90:
      5514-5518). Pyrenoid tubules do not contain these enzymes. The pyrenoid matrix
      consists of Rubisco but is devoid of the other photosynthetic enzymes
      investigated. Evidence for the occurrence of two Rubisco forms differing in their
      spatial localization has also been obtained: Rubisco form I appears to be
      membrane associated like other Calvin cycle components, whereas Rubisco form II
      is confined to the pyrenoid matrix. It is proposed that enzyme form I represents
      an active Rubisco when assembled into Calvin cycle enzyme complexes, whereas
      Rubisco form II may be part of a CO2-concentrating mechanism. Pyrenoidal Calvin
      cycle complexes are thought to be highly active in CO2 fixation and important for
      the synthesis of starch around the pyrenoid.

PMID- 12228444
TI  - The Binding Protein Associates with Monomeric Phaseolin.
AB  - The association of the binding protein (BiP) with newly synthesized proteins in
      the endoplasmic reticulum (ER) of developing bean (Phaseolus vulgaris)
      cotyledonary cells was investigated. ATP-sensitive association with many
      polypeptides was detected. The fraction of newly synthesized polypeptides
      associated with BiP varies among different proteins. The relationship between
      subunit assembly and binding to BiP was investigated in the case of the vacuolar
      trimeric glycoprotein phaseolin. In spite of the presence of a significant pool
      of phaseolin trimers in the ER, only monomeric phaseolin is found in association
      with BiP. On the whole, our results point to a general role of BiP in the
      synthesis of plant secretory proteins and indicate that, in the case of
      phaseolin, BiP binding sites are concealed during structural maturation in the
      ER, either before or upon formation of trimers. Our results also indicate that
      trimerization does not constitute a rate-limiting step in the transport of
      phaseolin to the protein storage vacuoles.

PMID- 12228445
TI  - Fructosyltransferase Activities in the Leaf Growth Zone of Tall Fescue.
AB  - High concentrations of water-soluble carbohydrates, mainly fructan, accumulate in
      the growth zone of tall fescue (Festuca arundinacea Schreb.) leaf blades. We
      studied sucrose-hydrolyzing activities in the leaf growth zone because of their
      importance in carbohydrate partitioning. Sucrose hydrolysis in the basal 1.5 cm
      was largely due to fructosyltransferases, which had activities up to 10 times
      higher than in fully developed leaf tissue. Three fructosyltransferases (F1, F2,
      and F3) were purified from the leaf growth zone. Each synthesized, from either
      sucrose or 1-kestose, a mixture of trisaccharides and higher-order oligofructans
      identical with the low-degree of polymerization fructan extracted from similar
      plant tissue. The highly purified fructosyltransferases retained ability (13%) to
      transfer fructose from sucrose to water. Time-dependent and substrate-dependent
      studies, using sucrose as the substrate, showed proportional production of
      fructose and glucose, indicating that both products are from the same enzyme.
      Fructosyltransferase was calculated to contribute about half the total transfer
      of fructose to water in the basal 1.5 cm. Invertase activity increased to near
      2.0 cm when fructosyl transfer to sucrose and other oligofructans decreased.
      Invertase was the major activity for sucrose hydrolysis at positions distal to
      3.0 cm.

PMID- 12228446
TI  - Molybdenum Cofactor Mutants, Specifically Impaired in Xanthine Dehydrogenase
      Activity and Abscisic Acid Biosynthesis, Simultaneously Overexpress Nitrate
      Reductase.
AB  - The molybdenum cofactor is shared by nitrate reductase (NR), xanthine
      dehydrogenase (XDH), and abscisic acid (ABA) aldehyde oxidase in higher plants
      (M. Walker-Simmons, D.A. Kudrna, R.L. Warner [1989] Plant Physiol 90:728-733). In
      agreement with this, cnx mutants are simultaneously deficient for these three
      enzyme activities and have physiological characteristics of ABA-deficient plants.
      In this report we show that aba1 mutants, initially characterized as ABA
      deficient mutants, are impaired in both ABA aldehyde oxidase and XDH activity but
      overexpress NR. These characteristics suggest that aba1 is in fact involved in
      the last step of molybdenum cofactor biosynthesis specific to XDH and ABA
      aldehyde oxidase; aba1 probably has the same function as hxB in Aspergillus. The
      significance of NR overexpression in aba1 mutants is discussed.

PMID- 12228447
TI  - Oleic Acid and Its Positional Isomer, cis-Vaccinic Acid, in the Appendix of
      Sauromatum guttatum during Anthesis.
AB  - The fatty acid profiles of various organs of the thermogenic inflorescence of
      Sauromatum guttatum and of the sporophylls of thermogenic male cones of two cycad
      species (Encephalartos ferox and Dioon edule var edule and var angustifolium)
      were determined by gas chromatography. During anthesis, palmitate (16:0), oleate
      [18:1 (9)], cis-vaccinate [18:1 (11)], and linoleate [18:2 (9, 12)] were the most
      abundant fatty acids in the Sauromatum appendix. cis-Vaccinic acid, a positional
      isomer of oleic acid, was identified by comparing its retention time on a gas
      chromatography column and its mass spectrum to an authentic compound. The
      percentage of oleic acid from total fatty acids dropped from about 9 in the
      morning 3 d before heat production to 6 in the morning 2 d before heat
      production. At this time, the percentage of cis-vaccinic acid increased from 3 to
      11%, and then remained at this level until the inflorescence dried and died.
      Palmitoleic acid [16:1 (9)], the common precursor of cis-vaccinic acid, is a
      minor component of total fatty acids. In six other organs of the Sauromatum
      inflorescence including thermogenic organs, such as male flowers and lower
      spadix, palmitate, oleate, and linoleate were prevalent but cis-vaccinate was
      not. The thermogenic male cones of the two cycad species were rich in palmitic,
      oleic, and linolenic acids. The level of cis-vaccinic acid in these organs was
      less than 0.5%.

PMID- 12228448
TI  - The 5[prime] Flanking Regions of Vicilin and Napin Storage Protein Genes Are Down
      Regulated by Desiccation in Transgenic Tobacco.
AB  - Drying of seeds, when imposed prematurely, elicits a switch in metabolism; events
      unique to development, such as synthesis of storage protein, are terminated,
      whereas syntheses associated with germination and growth are initiated. To
      determine the role of desiccation in down-regulating the expression of genes for
      storage proteins, the desiccation responsiveness of the 5[prime] and 3[prime]
      regulatory regions of the genes encoding the pea storage protein vicilin and the
      Brassica napus storage protein napin was tested in transgenic tobacco seed.
      Chimeric genes were introduced into tobacco; these genes consisted of the coding
      region of the reporter gene for [beta]-glucuronidase (GUS) and 5[prime] and/or
      3[prime] regions from the vicilin or napin genes or, as controls, the same
      regions derived from constitutively expressed genes, presumed to be desiccation
      insensitive. In transgenic seed expressing the gene constructs containing the
      vicilin or napin promoters, GUS activities declined during late seed development,
      and more dramatically, after imbibition of mature dry seed or prematurely dried
      seed. In contrast, GUS activities increased after seed rehydration when the
      constitutive viral promoter replaced the storage-protein gene 5[prime] region.
      Transient expression assays support the hypothesis that premature drying down
      regulates the expression of the storage-protein gene promoter. Following
      desiccation, this region may become insensitive to positive controlling factors;
      alternatively, changes to trans-acting factors may occur.

PMID- 12228449
TI  - The Plasma Membrane H+-ATPase (A Highly Regulated Enzyme with Multiple
      Physiological Functions).

PMID- 12228450
TI  - Partitioning of Intermediary Carbon Metabolism in Vesicular-Arbuscular
      Mycorrhizal Leek.
AB  - Vesicular-arbuscular mycorrhizal fungi are symbionts for a large variety of crop
      plants; however, the form in which they take up carbon from the host is not
      established. To trace the course of carbon metabolism, we have used nuclear
      magnetic resonance spectroscopy with [13C]glucose labeling in vivo and in
      extracts to examine leek (Allium porrum) roots colonized by Glomus etunicatum
      (and uncolonized controls) as well as germinating spores. These studies implicate
      glucose as a likely substrate for vesicular-arbuscular mycorrhizal fungi in the
      symbiotic state. Root feeding of 0.6 mM 1-[13C]glucose labeled only the fungal
      metabolites trehalose and glycogen. The time course of this labeling was
      dependent on the status of the host. Incubation with 50 mM 1-[13C]glucose caused
      labeling of sucrose (in addition to fungal metabolites) with twice as much
      labeling in uncolonized plants. There was no detectable scrambling of the label
      from C1 glucose to the C6 position of glucose moieties in trehalose or glycogen.
      Labeling of mannitol C1,6 in the colonized root tissue was much less than in
      axenically germinating spores. Thus, carbohydrate metabolism of host and fungus
      are significantly altered in the symbiotic state.

PMID- 12228451
TI  - A New Vertical Mesh Transfer Technique for Metal-Tolerance Studies in Arabidopsis
      (Ecotypic Variation and Copper-Sensitive Mutants).
AB  - A new vertical mesh transfer (VMT) technique has been developed to facilitate the
      rapid isolation of plant metal-tolerance mutants. The technique is quantitative,
      allowing comparisons of the growth responses of different strains or ecotypes.
      Using the VMT technique, we have characterized the dose responses of 10 ecotypes
      of Arabidopsis thaliana to Cu2+, Zn2+, Ni2+, Cr3+, Cd2+, and Al3+. Ecotypic
      variations in the highest concentration causing no inhibition and the lowest
      concentration causing complete inhibition for the six metals were observed. Two
      ecotypes, Ws and Enkheim, exhibited an inducible tolerance mechanism in response
      to copper. Pretreatment of Ws with the highest concentration causing no
      inhibition for copper resulted in a shifting of the lowest concentration causing
      complete inhibition to a higher value. Partial cross-induction and cross
      tolerance between Cu2+ and Zn2+ were demonstrated. In addition, ethyl
      methanesulfonate-mutagenized Columbia seeds were screened for copper-sensitive
      (cus) mutants using the VMT procedure. Thus far, 59 putative cus mutants have
      survived retesting to the M4 or M5 generation. When grown on gellan gum
      supplemented with 30 [mu]M CuCl2, cus mutants develop marked toxicity symptoms. A
      copper dose-response curve of the cus1 mutant showed that the metal-sensitive
      phenotype is specific for the lower concentration range.

PMID- 12228452
TI  - Low Temperature Induces the Accumulation of Phenylalanine Ammonia-Lyase and
      Chalcone Synthase mRNAs of Arabidopsis thaliana in a Light-Dependent Manner.
AB  - Anthocyanins, which accumulate in leaves and stems in response to low temperature
      and changes in light intensity, are synthesized through the phenylpropanoid
      pathway that is controlled by key enzymes that include phenylalanine ammonia
      lyase (PAL) and chalcone synthase (CHS). In this work we demonstrate that PAL and
      CHS mRNAs accumulate in leaves of Arabidopsis thaliana (L.) Heynh. upon exposure
      to low temperature in a light-dependent manner. The regulation of the PAL1 gene
      expression by low temperature and light was examined by analyzing the expression
      of the [beta]-glucuronidase (uidA) reporter gene in transgenic Arabidopsis plants
      containing the uidA gene of Escherichia coli under the control of the PAL1
      promoter. The results indicate that the accumulation of PAL1 mRNA is
      transcriptionally regulated. Histochemical staining for [beta]-glucuronidase
      activity showed that the PAL1 promoter is preferentially activated in
      photosynthetically active cells, paralleling anthocyanin accumulation. Moreover,
      we show that light may also be implicated in the regulation of the CHS gene in
      response to bacterial infiltration. Finally, using two transparent testa
      Arabidopsis mutants that are unable to accumulate anthocyanins, we demonstrate
      that these pigments are not required for successful development of freezing
      tolerance in this species.

PMID- 12228453
TI  - Induction of Anthocyanin Accumulation by Cytokinins in Arabidopsis thaliana.
AB  - Arabidopsis thaliana plants treated with exogenous cytokinins accumulate
      anthocyanin pigments. We have characterized this response because it is
      potentially useful as a genetic marker for cytokinin responsiveness. Levels of
      mRNAs for four genes of the anthocyanin biosynthesis pathway, phenylalanine
      ammonia lyase 1 (PAL1), chalcone synthase (CHS), chalcone isomerase (CHI), and
      dihydroflavonol reductase (DFR) were shown to increase coordinately in response
      to benzyladenine (BA). However, nuclear run-on transcription experiments
      suggested that although CHS and DFR are controlled by BA at the transcriptional
      level, PAL1 and CHI are controlled by BA posttranscriptionally. CHS mRNA levels
      increased within 2 h of BA spray application, and peaked by 3 h. Levels of PAL1
      mRNA did not increase within 6 h of BA spray. We also showed that PAL1, CHS, CHI,
      and DFR mRNA levels fluctuate during a 24-h period and appear to be controlled by
      a circadian clock. The relation between cytokinin regulation and light regulation
      of CHS gene transcription is discussed.

PMID- 12228454
TI  - Fructose-1,6-Bisphosphate Is an Allosteric Activator of Pyrophosphate:Fructose-6
      Phosphate 1-Phosphotransferase.
AB  - The activity of highly purified pyrophosphate:fructose-6-phosphate 1
      phosphotransferase (PFP) from barley (Hordeum vulgare) leaves was studied under
      conditions where the catalyzed reaction was allowed to approach equilibrium. The
      activity of PFP was monitored by determining the changes in the levels of
      fructose-6-phosphate, orthophosphate, and fructose-1,6-bisphosphate (Fru-1,6
      bisP). Under these conditions PFP activity was not dependent on activation by
      fructose-2,6-bisphosphate (Fru-2,6-bisP). Inclusion of aldolase in the reaction
      mixture temporarily restored the dependence of PFP on Fru-2,6-bisP.
      Alternatively, PFP was activated by Fru-1,6-bisP in the presence of aldolase. It
      is concluded that Fru-1,6-bisP is an allosteric activator of barley PFP, which
      can substitute for Fru-2,6-bisP as an activator. A significant activation was
      observed at a concentration of 5 to 25 [mu]M Fru-1,6-bisP, which demonstrates
      that the allosteric site of barley PFP has a very high affinity for Fru-1,6-bisP.
      The high affinity for Fru-1,6-bisP at the allosteric site suggests that the
      observed activation of PFP by Fru-1,6-bisP constitutes a previously unrecognized
      in vivo regulation mechanism.

PMID- 12228455
TI  - Subcellular Compartmentation of the 4-Aminobutyrate Shunt in Protoplasts from
      Developing Soybean Cotyledons.
AB  - The subcellular localization of enzymes involved in the 4-ami-nobutyrate shunt
      was investigated in protoplasts prepared from developing soybean [Glycine max
      (L.) Merrill cv Maple Arrow] cotyledons. Protoplast lysate was fractionated by
      differential and continuous Percoll-gradient centrifugation to separate organelle
      fractions. Glutamate decarboxylase (EC 4.1.1.15) was found exclusively in the
      cytosol, whereas 4-aminobutyrate:pyruvate transami-nase (EC 2.6.1.19) and
      succinic semialdehyde dehydrogenase (EC 1.2.1.16) were associated exclusively
      with the mitochondrial fractions. Mitochondrial fractions also catabolized [U
      14C]4-aminobu-tyrate to labeled succinate.

PMID- 12228456
TI  - Identification of the Plasma Membrane Ca2+-ATPase and of Its Autoinhibitory
      Domain.
AB  - The effect of controlled proteolysis on the plasma membrane (PM)Ca2+-ATPase was
      studied at the molecular level in PM purified from radish (Raphanus sativus L.)
      seedlings. Two new methods for labeling the PM Ca2+-ATPase are described. The PM
      Ca2+-ATPase can be selectively labeled by treatment with micromolar fluorescein
      isothiocyanate (FITC), a strong inhibitor of enzyme activity. Both inhibition of
      activity and FITC binding to the PM Ca2+-ATPase are suppressed by millimolar
      MgITP. The PM Ca2+-ATPase maintains the capability to bind calmodulin also after
      sodium dodecyl sulfate gel electrophoresis and blotting; therefore, it can be
      conveniently identified by 125l-calmodulin overlay in the presence of calcium.
      With both methods a molecular mass of 133 kD can be calculated for the PM Ca2+
      ATPase. FITC-labeled PM Ca2+-ATPase co-migrates with the phosphorylated
      intermediate of the enzyme[mdash]labeled by incubation with [[gamma]-32P]GTP in
      the presence of calcium[mdash]on acidic sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Controlled trypsin treatment of purified PM determines a
      reduction of the molecular mass of the PM Ca2+-ATPase from 133 to 118 kD parallel
      to the increase of enzyme activity. Only the 133-kD but not the 118-kD PM Ca2+
      ATPase binds calmodulin. These results indicate that trypsin removes from the PM
      Ca2+-ATPase an autoinhibitory domain that contains the calmodulin-binding domain
      of the enzyme.

PMID- 12228457
TI  - Similarities in Gene Expression during the Postharvest-Induced Senescence of
      Spears and Natural Foliar Senescence of Asparagus.
AB  - Changes in gene expression and tissue composition were investigated during foliar
      development and natural senescence of asparagus (Asparagus officinalis L.). Three
      phases in development and senescence of the foliage were characterized: early
      fern growth, mature fern, and senescence, when a marked loss of chlorophyll,
      sucrose, and protein occurred and major changes in translatable mRNAs were
      detected. Transcripts for three asparagus spear harvest-induced cDNA clones,
      pTIP9, pTIP11, and pTIP12 (G.A. King and K.M. Davies [1992] Plant Physiol 100:
      1661-1669), accumulated during natural foliar senescence, suggesting that the
      underlying regulatory mechanisms may be similar in both developmental situations.
      We have used our knowledge of asparagus spear physiology, the probable proteins
      encoded by the cDNA clones, and our fern development data to propose that sugar
      depletion regulates the accumulation of at least pTIP12 transcripts in senescing
      asparagus tissue.

PMID- 12228458
TI  - The Xanthophyll Cycle in Intermittent Light-Grown Pea Plants (Possible Functions
      of Chlorophyll a/b-Binding Proteins).
AB  - The xanthophyll cycle in pea (Pisum sativum L. cv Kleine Rheinlanderin) plants
      has been investigated in vivo. Control plants were compared with those grown
      under intermittent light (IML plants). IML plants are particularly characterized
      by the absence of nearly all chlorophyll a/b-binding proteins. The rates of de
      epoxidation during 30 min of illumination and their dependence on the incident
      photon flux density (PFD) have been determined. They were very similar in both
      types of plants, with the exception that IML plants contained, at any PFD, much
      higher zeaxanthin concentrations in the steady state (reached after about 15 min
      of illumination) than control plants. This indicates that the amount of
      convertible violaxanthin under illumination is dependent on the presence of
      chlorophyll a/b-binding proteins. The epoxidation rate (examined at a PFD of 15
      [mu]E m-2 s-1, after 15 min of preillumination with different PFDs) showed
      significant differences between the two types of plants. It was about 5-fold
      slower in IML plants. On the other hand, in both types of plants, the epoxidation
      rate decreased with increasing PFD during preillumination. Prolonged
      preillumination at high PFDs resulted in a decrease of the epoxidation rate
      without a further increase of the zeaxanthin concentration in both continuous
      light and IML plants. This result argues against a permanent turnover of the
      xanthophylls under illumination, at least at high PFDs.

PMID- 12228459
TI  - Effect of Vernalization, Photoperiod, and Light Quality on the Flowering
      Phenotype of Arabidopsis Plants Containing the FRIGIDA Gene.
AB  - We have compared the flowering response to vernalization, photoperiod, and far
      red (FR) light of the Columbia (Col) and Landsberg erecta (Ler) ecotypes of
      Arabidopsis into which the flowering-time locus FRIGIDA (FRI) has been
      introgressed with that of the wild types Col, Ler, and San Feliu-2 (Sf-2). In the
      early-flowering parental ecotypes, Col and Ler, a large decrease in flowering
      time in response to vernalization was observed only under short-day conditions.
      However, Sf-2 and the Ler and Col genotypes containing FRI showed a strong
      response to vernalization when grown in either long days or short days. Although
      vernalization reduced the responsiveness to photoperiod, plants vernalized for
      more than 80 d still showed a slight photoperiod response. The effect of FRI on
      flowering was eliminated by 30 to 40 d of vernalization; subsequently, the
      response to vernalization in both long days and short days was the same in Col
      and Ler with or without FRI. FR-light enrichment accelerated flowering in all
      ecotypes and introgressed lines. However, the FR-light effect was most
      conspicuous in the FRI-containing plants. Saturation of the vernalization effect
      eliminated the effect of FR light on flowering, although vernalization did not
      eliminate the increase of petiole length in FR light.

PMID- 12228460
TI  - Chlorophyll Fluorescence Induction in Leaves of Phaseolus vulgaris Infected with
      Bean Rust (Uromyces appendiculatus).
AB  - To our knowledge, this report describes the first application of video imaging of
      Chl fluorescence to the study of light utilization in photosystem II of attached
      leaves of Phaseolus vulgaris infected with the obligate biotrophic fungus
      Uromyces appendiculatus (race 38). The video-based detection system produced a
      spatially resolved, quantifiable signal that was highly specific for chlorophyll
      fluorescence. Video images of spatial variation in the initial stage of the
      fluorescence induction (dark-light) transient revealed discreet regions of
      intense emission coinciding with centers of subsequent lesion development and
      accompanying chlorosis. Incipient lesions were visible by this procedure 3 d
      following inoculation, fully 3 to 4 d prior to visible symptoms. Fluorescence
      emission patterns in infected areas during the induction transient were
      heterogeneous with radial distance from the point of invasion and varied with the
      length of the time delay between re-illumination and image capture. During later
      ([greater than or equal to]1 min) stages of the induction transient, fluorescence
      emission in incipient lesions was quenched compared to surrounding tissue. These
      essential features of the induction transient observed in video images were also
      noted when individual lesions were examined using pulse modulation fluorimetry.

PMID- 12228461
TI  - Measurement of the Leakage of CO2 from Bundle-Sheath Cells of Leaves during C4
      Photosynthesis.
AB  - During C4 photosynthesis, CO2 is released in bundle-sheath cells by
      decarboxylation of C4 acids and then refixed via ribulose-1,5-bisphosphate
      carboxylase. In this study we examined the efficiency of this process by
      determining the proportion of the released CO2 that diffuses back to mesophyll
      cells instead of being refixed. This leak of CO2 was assessed by determining the
      amount of 14CO2 released from leaves during a chase in high [12CO2] following a
      70-s pulse in 14CO2. A computer-based analysis of the time-course curve for 14CO2
      release indicated a first-order process and provided an estimate of the initial
      velocity of 14CO2 release from leaves. From this value and the net rate of
      photosynthesis determined from the 14CO2 fixed in the pulse, the CO2 leak rate
      from bundle-sheath cells (expressed as a percentage of the rate of CO2 production
      from C4 acids) could be deduced. For nine species of Gramineae representing the
      different subgroups of C4 plants and two NAD-malic enzyme-type dicotyledonous
      species, the CO2 leak ranged between 8 and 14%. However, very high CO2 leak rates
      (averaging about 27%) were recorded for two NADP-malic enzyme-type dicotyledonous
      species of Flaveria. The results are discussed in terms of the efficiency of C4
      photosynthesis and observed quantum yields.

PMID- 12228462
TI  - Low Activation State of Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase in
      Carboxysome-Defective Synechococcus Mutants.
AB  - The high-CO2-requiring mutant of Synechococcus sp. PCC 7942, EK6, was obtained
      after extension of the C terminus of the small subunit of ribulose-1,5
      bisphosphate (RuBP) carboxylase/oxygenase (Rubisco). The carboxysomes in EK6 were
      much larger than in the wild type, but the cellular distribution of the large and
      small sub-units of Rubisco was not affected. The kinetic parameters of in vitro
      activated Rubisco were similar in EK6 and in the wild type. On the other hand,
      Rubisco appeared to be in a low state of activation in situ in EK6 cells
      pretreated with an air level of CO2. This was deduced from the appearance of a
      lag phase when carboxylation was followed with time in cells permeabilized by
      detergent and subsequently supplied with saturating CO2 and RuBP. Pretreatment of
      the cells with high CO2 virtually abolished the lag. After low-CO2 treatment, the
      internal RuBP pool was much higher in mutant cells than in the wild-type cells;
      pretreatment with high CO2 reduced the pool in mutant cells. We suggest that the
      high-CO2-requiring phenotype in mutants that possess aberrant carboxysomes arises
      from the inactivated state of Rubisco when the cells are exposed to low CO2.

PMID- 12228463
TI  - Lipid Composition and Protein Dynamics in Thylakoids of Two Wheat Cultivars
      Differently Sensitive to Drought.
AB  - Two wheat (Triticum durum Desf.) cultivars with different sensitivities to
      drought were either grown under regular irrigation or subjected to water deficit
      by withholding water for 14 d. Water-stressed plants of both cultivars underwent
      similar decreases in leaf water potential, but the drought-tolerant cultivar
      showed higher relative water content and turgor. Neither osmotic nor elastic
      adjustment mechanisms appeared to be active under the conditions described here.
      Thylakoids isolated from the stressed, drought-tolerant wheat showed an increase
      in lipid-to-protein ratio, in comparison with the control, whereas this ratio
      remained unchanged in the sensitive wheat. In both cultivars, water deficit
      determined different rearrangements in the composition of the thylakoid
      individual polar lipids, but their unsaturation level remained unaffected with
      the exception of monogalactosyldiacylglycerol. In the drought-sensitive cultivar,
      an accumulation of free fatty acids together with a reduction in polar lipid
      amount was observed. Electron paramagnetic resonance measurements of spin-labeled
      proteins of stressed plants from the sensitive cv Adamello showed a higher spin
      label rotational correlation time together with lower sulphydryl group and mobile
      proteic portion levels, in comparison with the control. In the tolerant cv
      Ofanto, the first two parameters changed to a lesser extent following water
      depletion, and the mobile proteic portion was not altered.

PMID- 12228464
TI  - Allene Oxide Synthase and Allene Oxide Cyclase, Enzymes of the Jasmonic Acid
      Pathway, Localized in Glycine max Tissues.
AB  - Because jasmonic acid regulates a number of processes, including the expression
      of vegetative storage proteins in soybean (Glycine max L.) leaves, the relative
      activity of a specific portion of the jasmonic acid biosynthetic pathway in
      soybean tissues was examined. Allene oxide synthase and allene oxide cyclase were
      examined because they constitute a branch point leading specifically from 13(S)
      hydroperoxy-9(Z), 11(E), 15(Z)-octadecatrienoic acid to 12-oxo-phytodienoic acid,
      the precursor of jasmonic acid. From growing plants, seed coats (hila plus
      testae) of green fruits (38 d post-anthesis) were most active, eliciting about
      1.5 times greater activity on a per milligram of protein basis than the next most
      active tissue, which was the pericarp. Leaves from fruiting plants were only one
      seventh as active as seed coats, and activities in both immature cotyledons and
      embryonic axes were very low. No activity was detected in any part of stored,
      mature seeds. After 72 h of germination of stored seeds, a small amount of
      activity, about 4% of that in immature seed coats, was found in the plumule
      hypocotyl-root, and no activity was detected in the cotyledons. The high levels
      of jasmonic acid biosynthetic enzymes in soybean pericarp and seed coat suggest a
      role for jasmonic acid in the transfer of assimilate to seeds.

PMID- 12228465
TI  - The Role of Pea Chloroplast [alpha]-Glucosidase in Transitory Starch Degradation.
AB  - Pea chloroplastic [alpha]-glucosidase (EC 3.2.1.20) involved in transitory starch
      degradation was purified to apparent homogeneity by ion exchange, reactive dye,
      hydroxylapatite, hydrophobic interaction, and gel filtration column
      chromatography. The native molecular mass and the subunit molecular mass were
      about 49.1 and 24.4 kD, respectively, suggesting that the enzyme is a homodimer.
      The enzyme had a Km of 7.18 mM for maltose. The enzyme's maximal activity at pH
      7.0 and stability at pH 6.5 are compatible with the diurnal oscillations of the
      chloroplastic stromal pH and transitory starch accumulation. This pH modulation
      of the [alpha]-glucosidase's activity and stability is the only mechanism known
      to regulate starch degradative enzymes in leaves. Although the enzyme was
      specific for the [alpha]-D-glucose in the nonreducing end as the glycon, the
      aglycon moieties could be composed of a variety of groups. However, the
      hydrolysis rate was greatly influenced by the aglycon residues. Also, the enzyme
      could hydrolyze glucans in which carbon 1 of the glycon was linked to different
      carbon positions of the penultimate glucose residue. The ability of the [alpha]
      glucosidase to hydrolyze [alpha]-1,2- and [alpha]-1,3-glucosidic bonds may be
      vital if these bonds exist in starch granules because they would be barriers to
      other starch degradative enzymes. This purified pea chloroplastic [alpha]
      glucosidase was demonstrated to initiate attacks on native transitory
      chloroplastic starch granules.

PMID- 12228466
TI  - Antibodies That Distinguish between the Serine-158 Phospho- and Dephospho-Form of
      Spinach Leaf Sucrose-Phosphate Synthase.
AB  - Serum antibodies were raised against a synthetic peptide corresponding to the
      amino acid sequence surrounding the major inactivating phosphorylation site
      (serine-158) of spinach (Spinacia oleracea) leaf sucrose-phosphate synthase
      (SPS). The anti-peptide antibodies precipitated highly activated SPS
      preferentially to ATP-inactivated SPS and interacted only weakly with the sodium
      dodecyl sulfate-denatured enzyme bound to a membrane. The antibodies blocked
      phosphorylation but not dephosphorylation of SPS. Highly activated SPS was not
      entirely dephosphorylated and ATP-inactivated SPS was not completely
      phosphorylated on serine-158, as indicated by the sensitivities of immunopurified
      serine-158 phospho- and dephospho-SPS to inhibition by inorganic phosphate. The
      anti-peptide antibodies can be used to detect changes in the phosphorylation
      state of serine-158, and they are useful to purify and characterize distinct
      kinetic forms of SPS.

PMID- 12228467
TI  - Ultraviolet Light Inhibition of Phytochrome-Induced Flavonoid Biosynthesis and
      DNA Photolyase Formation in Mustard Cotyledons (Sinapis alba L.).
AB  - In cotyledons of etiolated mustard (Sinapis alba L.) seedlings, phytochrome-far
      red-absorbing form-induced flavonoid biosynthesis was found to be inhibited by
      short-term ultraviolet (UV) irradiations. UV inhibition was shown for the
      synthesis of quercetin, anthocyanin, and also for the accumulation of the mRNA
      for chalcone synthase, the key enzyme of this pathway. The UV effect was more
      pronounced on flavonoid biosynthesis, a process that selectively occurs in the
      epidermal layers, than on the synthesis of mRNA for chlorophyll a/b-binding
      protein localized in the mesophyll tissue. These UV inhibitory effects were
      accompanied by cyclobutane pyrimidine dimer (CPD) formation showing a linear
      fluence-response relationship. CPD formation and UV inhibition of flavonoid
      biosynthesis was found to be partially reversible by blue/UV-A light via DNA
      photolyase (PRE), allowing photoreactivation of the DNA by splitting of CPDs,
      which are the cause of the UV effect. Like flavonoid formation PRE was also
      induced by the far-red-absorbing form of phytochrome and induction was inhibited
      by UV. A potential risk of inhibition, in response to solar UV-B irradiation, was
      shown for anthocyanin formation. This inhibition, however, occurred only if
      photoreactivation was experimentally reduced. The PRE activity present in the
      etiolated seedlings (further increasing about 5-fold during light
      acclimatization) appears to be sufficient to prevent the persistence of CPDs even
      under conditions of high solar irradiation.

PMID- 12228468
TI  - Oxygen-Induced Membrane Depolarizations in Legume Root Nodules (Possible Evidence
      for an Osmoelectrical Mechanism Controlling Nodule Gas Permeability).
AB  - Various stresses trigger rapid and reversible decreases in the O2 permeability
      (PO) of legume root nodules. Several possible mechanisms have been proposed, but
      no supporting data have previously been presented that meet the requirements for
      both rapidity and reversibility. Stomatal regulation of gas permeability in
      leaves involves electrically driven fluxes of inorganic osmoticants, so we
      investigated the possibility of a somewhat similar mechanism in nodules. We used
      microelectrodes to monitor membrane potential in intact, attached nodules of
      Glycine max, Medicago sativa, Lotus corniculatus, and Trifolium repens while
      controlling external O2 concentration and, in the case of G. max, measuring PO
      with a nodule oximeter. A 1- to 2-min exposure to 100 kPa O2 was found to induce
      rapid and reversible membrane depolarizations in nodules of each species. This
      depolarization (which, to our knowledge, is unique to nodules) is accompanied by
      reversible decreases in PO in G. max nodules. An osmoelectrical mechanism for
      control of nodule gas permeability, consistent with these data, is presented.

PMID- 12228469
TI  - Inhibition of Maize Root H+-ATPase by Fluoride and Fluoroaluminate Complexes.
AB  - Vesicles derived from maize roots retain a membrane-bound H+-ATPase that is able
      to pump H+ at the expense of ATP hydrolysis. The H+ pumping and the ATPase
      activity of these vesicles are inhibited by lithium fluoride and by the complex
      formed between fluoride and aluminum. The inhibition promoted by lithium fluoride
      increases as the MgCl2 concentration in the medium is increased from 2 to 20 mM.
      The inhibitory activity of both lithium fluoride and aluminum fluoride increases
      as the temperature of the medium is increased from 20 to 35[deg]C. Inorganic
      phosphate (10-40 mM) inhibits the H+ -ATPase at pH 6.5 but not at pH 7.0, and at
      both pH values, it antagonizes the inhibition promoted by lithium fluoride and
      fluoroaluminate complexes.

PMID- 12228470
TI  - Induction of CO2 and Bicarbonate Transport in the Green Alga Chlorella
      ellipsoidea (I. Time Course of Induction of the Two Systems).
AB  - Changes in the physiological properties of the green alga Chlorella ellipsoidea
      (UTEX 20) were determined during adaptation from high CO2 to air. Cells of C.
      ellipsoidea, grown in high CO2, had an extremely low affinity for dissolved
      inorganic carbon (DIC). However, high-affinity DIC transport was induced rapidly
      after switching to air, which caused a massive decrease in the DIC concentration
      in the medium. Rates of O2 evolution without added carbonic anhydrase (CA) were
      compared with calculated rates of uncatalyzed CO2 formation in the medium as a
      measure of active HCO3-uptake. Cells were found to be able to use HCO3- after 5 h
      of adaptation and this capacity increased during the next 17 h. The stimulation
      of O2 evolution upon CA addition was used as a measurement of active CO2
      transport: such stimulation occurred 2 h after transfer and increased during the
      next 5 h. Increases in O2 evolution rates were correlated closely with an
      increasing capacity to accumulate intracellular pools of acid-labile DIC and with
      decreases in K1/2(CO2) and CO2-compensation point of the cells. Treatment of
      cells with cycloheximide (5 [mu]g mL-1) during adaptation completely inhibited
      DIC transport induction, whereas treatment with chloramphenicol (400 [mu]g mL-1)
      had no effect, indicating the requirement for cytoplasmic protein synthesis in
      the induction. These results suggest that both CO2 and HCO3- transport are
      induced upon transfer of cells from high CO2 to air and that there is a temporal
      separation between the induction of the two systems.

PMID- 12228471
TI  - Induction of CO2 and Bicarbonate Transport in the Green Alga Chlorella
      ellipsoidea (II. Evidence for Induction in Response to External CO2
      Concentration).
AB  - The critical species and concentrations of dissolved inorganic carbon (DIC)
      required for the induction of DIC transport during adaptation to low CO2 were
      determined for the green alga Chlorella ellipsoidea. The concentration of
      dissolved CO2 needed for the induction of both CO2 and HCO3- transport was
      independent of pH during adaptation, whereas the total DIC concentration required
      increased at alkaline pH. At pH 7.5, the minimum equilibrium DIC concentration at
      which high CO2 characteristics were maintained, i.e. transport was repressed, was
      2100 [mu]M, whereas the maximum equilibrium DIC concentration below which DIC
      transport was fully induced (DICIND) was 500 [mu]M. Intracellular DIC
      concentration during adaptation to DICIND decreased temporarily after 2 h to 60%
      of the maximum level but recovered after 3 h of adaptation. After 3 h of
      adaptation to DICIND, cells exhibited maximum O2 evolution rate at DICIND. When
      cells partially adapted to DICIND were returned to high CO2, there was an
      immediate halt to the induction of transport and a gradual decrease in transport
      capacity over 23 h. The capacity for the induction of transport was unaffected by
      the absence of light. These results indicate that changes in the internal DIC
      pool during adaptation to low CO2 do not trigger the induction of DIC transport
      and that the induction is not light dependent. Induction of DIC transport in C.
      ellipsoidea appears to occur in response to the continuous exposure of cells to a
      critical CO2 concentration in the external medium.

PMID- 12228472
TI  - Subcellular Localization and Characterization of Excessive Iron in the
      Nicotianamine-less Tomato Mutant chloronerva.
AB  - To understand the function of the Fe2+-complexing compound nicotianamine (NA) in
      the iron metabolism of plants we have localized iron and other elements in the NA
      containing tomato wild type (Lycopersicon esculentum) and its NA-free mutant
      chloronerva by quantitative x-ray microanalysis. Comparison of element
      composition of the rhizodermal cell walls indicated that the wild type
      accumulated considerable amounts of iron and phosphorus in the cell wall, whereas
      in the mutant iron and phosphorus were detected in the cytoplasm and vacuoles of
      the rhizodermis. In mutant leaves containing high iron concentrations in the
      symplast, electron-dense inclusions were detected in chloroplasts and phloem.
      Such particles, consisting mainly of iron and phosphorus, were never found in the
      wild type and were very rarely detected in young chlorotic mutant leaves or after
      treatment of the mutant with NA. For further characterization the electron-dense
      inclusions in mutant leaves were isolated and compared by sodium dodecyl sulfate
      gel electrophoresis and immunoblotting to ferritin from iron-loaded Phaseolus
      vulgaris leaves. Antibodies raised against purified Phaseolus leaf ferritin were
      used. Neither in mutant nor in wild type (iron loaded and control) was ferritin
      protein detected. These results suggest that the electron-dense inclusions in
      mutant leaves are not identical with ferritin. It is concluded that NA is
      necessary to complex ferrous iron in a soluble and available form within the
      cells. In the absence of NA the precipitation of excessive iron in the form of
      insoluble ferric phosphate compounds could protect the cells from iron overload.

PMID- 12228473
TI  - Measurements of in Vivo Ubiquinone Reduction Levels in Plant Cells.
AB  - A method is described for the determination of in vivo ubiquinone (UQ) reduction
      levels in nongreen tissues by extraction and subsequent detection of ubiquinone
      10 and ubiquinol-10 with high-performance liquid chromatography. In Petunia
      hybrida cell suspensions UQ reduction remained at a stable level of about 60%,
      despite the changing conditions during the batch culture (from excess sugar to
      starvation) and the concomitant variations in respiration. Also, in the presence
      of uncoupler, which causes a large increase in respiration via both the
      cytochrome pathway and the alternative pathway, UQ reduction levels stayed at
      60%. In mitochondria isolated from these cells, activity of the alternative
      pathway was only observed at UQ reduction levels higher than 80%. It is proposed
      that in vivo the relationship between UQ reduction and the activity of the
      alternative oxidase is modulated by mechanisms such as thiol modifications and
      accumulation of organic acids. Accordingly, pyruvate concentration in P. hybrida
      cells increased in the presence of uncoupler.

PMID- 12228474
TI  - Lack of Control in Inorganic Phosphate Uptake by Catharanthus roseus (L.) G. Don
      Cells (Cytoplasmic Inorganic Phosphate Homeostasis Depends on the Tonoplast
      Inorganic Phosphate Transport System?).
AB  - Inorganic phosphate (Pi) uptake by Catharanthus roseus (L.) G. Don cells was
      studied in relation to its apparent uncontrolled uptake using 31P-nuclear
      magnetic resonance spectroscopy. Kinetics of Pi uptake by the cells indicated
      that apparent Km and Vm were about 7 [mu]M and 20 [mu]mol g-1 fresh weight h-1,
      respectively. Pi uptake in Murashige-Skoog medium under different Pi
      concentrations and different initial cell densities followed basically the same
      kinetics. When supplied with abundant Pi, cells absorbed Pi at a constant rate
      (Vm) for the first hours and accumulated it in the vacuole. As the endogenous
      pool expanded, the rate of Pi uptake gradually decreased to nil. Maximum Pi
      accumulation was 100 to 120 [mu]mol g-1 fresh weight if cell swelling during Pi
      uptake (about 2-fold in cell volume) was not considered. Results indicated that
      (a) the rate of Pi uptake by Catharanthus cells was independent of initial cell
      density and was constant over a wide range of Pi concentrations (2 mM to about 10
      [mu]M) unless the cells were preloaded with excess Pi, and (b) there was no
      apparent feedback control over the Pi uptake process in the plasma membrane to
      avoid Pi toxicity. The importance of the tonoplast Pi transport system in
      cytoplasmic Pi homeostasis is discussed.

PMID- 12228475
TI  - Rapid Response of the Yield Threshold and Turgor Regulation during Adjustment of
      Root Growth to Water Stress in Zea mays.
AB  - Responses of cortical cell turgor (P) following rapid changes in osmotic pressure
      ([pi]m) were measured throughout the elongation zone of maize (Zea mays L.) roots
      using a cell pressure probe and compared with simultaneously measured root
      elongation to evaluate: yield threshold (Y) (minimum P for growth), wall
      extensibility, growth-zone radial hydraulic conductivity (K), and turgor recovery
      rate. Small increases in [pi]m (0.1 MPa) temporarily decreased P and growth,
      which recovered fully in 5 to 10 min. Under stronger [pi]m (up to 0.6 MPa),
      elongation stopped for up to 30 min and then resumed at lower rates. Recoveries
      in P through solute accumulation and lowering of Y enabled growth under water
      stress. P recovery was as much as 0.3 MPa at [pi]m = 0.6 MPa, but recovery rate
      declined as water stress increased, suggesting turgor-sensitive solute transport
      into the growth zone. Under strong [pi]m, P did not recover in the basal part of
      the growth zone, in conjunction with a 30% shortening of the growth zone. Time
      courses showed Y beginning to decrease within several minutes after stress
      imposition, from about 0.65 MPa to a minimum of about 0.3 MPa in about 15 min.
      The data concerning Y were not confounded significantly by elastic shrinkage. K
      was high (1.3 x 10-10 m2 s-1 MPa-1), suggesting very small growth-induced water
      potential gradients.

PMID- 12228476
TI  - Photosynthetic Nitrite Reduction as Influenced by the Internal Inorganic Carbon
      Pool in Air-Grown Cells of Synechococcus UTEX 625.
AB  - Photosynthetic reduction of NO2- was studied in air-grown cells of a
      cyanobacterium, Synechococcus UTEX 625. Addition of NO2- resulted in significant
      amounts of chlorophyll a fluorescence quenching both in the absence and presence
      of CO2, fixation inhibitors, glycolaldehyde or iodoacetamide. The degree of NO2-
      quenching was insensitive to the O2 concentration in the medium. Addition of 100
      [mu]M inorganic carbon in the presence of glycolaldehyde and O2, leading to
      formation of the carbon pool within the cells, resulted in pronounced
      fluorescence quenching. Removal of O2 from the medium restored the fluorescence
      yield completely, and the subsequent addition of NO2- quenched 36% of the
      variable fluorescence. From the response to added 3-(3,4-dichlorophenyl)-1,1
      dimethylurea, the quenching by NO2- appeared to be photochemical quenching, and
      nonphotochemical quenching did not seem to be present. The reduction of NO2-
      observed on its addition to inorganic carbon-depleted cells remained uninfluenced
      by O2 or glycolaldehyde. The internal inorganic carbon pool in the cells
      stimulated NO2- reduction, both in the presence and absence of O2, by 4.8-fold.
      An increase in NO2- reduction by 0.5-fold was also observed in the presence of O2
      during simultaneous assimilation of carbon and nitrogen in inorganic carbon
      depleted cells. Contrary to this, under anaerobiosis, NO2- reduction was
      suppressed when carbon and nitrogen assimilation occurred together.

PMID- 12228477
TI  - The Metabolism of Quinate in Pea Roots (Purification and Partial Characterization
      of a Quinate Hydrolyase).
AB  - A quinate (QA) hydrolyase was isolated from pea (Pisum sativum L.) roots. The
      enzyme converts QA into shikimate by elimination of water. The enzymatic reaction
      is independent of cofactors and divalent cations. The QA hydrolyase was purified
      about 1,600-fold to apparent electrophoretic homogeneity in three steps,
      including bovine serum albumin-affinity chromatography. The enzyme forms
      oligomers and/or complexes with bovine serum albumin and ovalbumin. The monomer
      molecular weight of the enzyme is about 15,000. The hydrolyase shows regular
      Michaelis-Menten kinetics with a Km, of 2.0 mM for QA. Compartmentation studies
      reveal that the QA hydrolyase is localized in plastids. The QA hydrolyase may
      function in channeling imported QA into the shikimate pathway to support aromatic
      amino acid biosynthesis in plastids.

PMID- 12228478
TI  - Genetic Regulation of Development in Sorghum bicolor (IX. The ma3R Allele
      Disrupts Diurnal Control of Gibberellin Biosynthesis).
AB  - The diurnal regulation of gibberellin (GA) concentrations in Sorghum bicolor was
      studied in a mutant lacking a light-stable 123-kD phytochrome (ma3Rma3R), wild
      type (ma3ma3,Ma3Ma3), and heterozygous (ma3ma3R) cultivars. GAs were determined
      in shoots of 14-d-old plants by gas chromatography-selected ion-monitoring-mass
      spectrometry. GA12 levels fluctuated rhythmically in Ma3Ma3, ma3ma3,
      and,ma3Rma3R; Peak levels occured 3 to 9 h after lights-on. In some experiments,
      GA53 levels followed a similar pattern. There was no rhythmicity in levels of
      GA19 and GA8 in any genotype. In ma3ma3 and Ma3Ma3, GA20 levels increased at
      lights-on, peaked in the afternoon, and decreased to minimum levels in darkness.
      In ma3Rma3R, peak GA20 levels occured at lights-on, 9 h earlier than in the wild
      type genotypes. The pattern for GA1 levels closely followed GA20 levels in all
      cultivars. One copy of ma3 restored near wild-type regulation of GA20 levels. GA
      rhythms persisted in 25-d-old ma3ma3 plants. Since absence of the 123-kD
      phytochrome disrupted diurnal regulation of the GA19 -> GA20 step, the ma3Rma3R
      genotype may be viewed as being phase shifted in the rhythmic levels of GA20 and
      GA1 rather than as simply overproducing them.

PMID- 12228479
TI  - Genetic Regulation of Development in Sorghum bicolor (X. Greatly Attenuated
      Photoperiod Sensitivity in a Phytochrome-Deficient Sorghum Possessing a
      Biological Clock but Lacking a Red Light-High Irradiance Response).
AB  - The role of a light-stable, 123-kD phytochrome in the biological clock, in
      photoperiodic flowering and shoot growth in extended photoperiods, and in the red
      light-high irradiance response was studied in Sorghum bicolor using a phytochrome
      deficient mutant, 58M (ma3R ma3R), and a near-isogenic wild-type cultivar, 100M
      (Ma3 Ma3). Since chlorophyll a/b-binding protein mRNA and ribulose bisphosphate
      carboxylase small subunit mRNA cycled in a circadian fashion in both 58M and 100M
      grown in constant light, the 123-kD phytochrome absent from 58M does not appear
      necessary for expression or entrainment of a functional biological clock.
      Although 58M previously appeared photoperiod insensitive in 12-h photoperiods,
      extending the photoperiod up to 24 h delayed floral initiation for up to 2 weeks
      but did not much affect shoot elongation. Thus, although 58M flowers early in
      intermediate photoperiods, a residual photoperiod sensitivity remains that
      presumably is not due to the missing 123-kD phytochrome. Since rapid shoot
      elongation persists in 58M under extended photoperiods despite delayed floral
      initiation, long photoperiods uncouple those processes. The observed absence of a
      red light-high irradiance response in 58M, in contrast to the presence of the
      response in 100M, strengthens the suggestion that the 123-kD phytochrome missing
      from 58M is a phyB.

PMID- 12228480
TI  - A Noninvasive Technique for Monitoring Peroxidative and H2O2-Scavenging
      Activities during Interactions between Bacterial Plant Pathogens and Suspension
      Cells.
AB  - Stimulation of active oxygen metabolism occurs during the early stages of
      interactions involving bacteria and plant cell suspensions. Although many
      cellular processes are known to affect active oxygen metabolism in plants, it is
      not known which of these factors affect active oxygen levels during plant
      bacteria interactions. Extracellular peroxidases have been shown to participate
      in both the production and utilization of active oxygen species such as H2O2 and
      superoxide. Catalase and other scavenging mechanisms also affect the overall
      level of active oxygen. In this study the luminol-dependent chemiluminescent
      reaction previously used to measure H2O2 levels in suspension cells was modified
      to allow the assay of both peroxidase and H2O2-scavenging activity. The early
      stages of the interactions between tobacco (Nicotiana tabacum) and Pseudomonas
      syringae pv syringae, as well as between soybean (Glycine max) and P. syringae pv
      glycinea, were investigated. This method of monitoring peroxidase and H2O2
      scavenging activity proved to be rapid, sensitive, and nonintrusive, allowing the
      processing of multiple samples using intact cells or cell-free preparations. The
      results from the study demonstrate that the scavenging activities can be
      significant and must be considered when studying active oxygen production in
      biological interactions.

PMID- 12228481
TI  - Differential Regulation of ADP-Glucose Pyrophosphorylase in the Sink and Source
      Tissues of Potato.
AB  - Expression of potato (Solanum tuberosum L.) ADP-Glc pyrophosphorylase (AGP) was
      analyzed to assess whether the expression patterns of the individual subunit
      genes play a role in effectuating AGP activity and hence starch biosynthesis.
      Temporal analysis revealed that the coordinate expression of the large (IAGP) and
      small (sAGP) subunits, which collectively make up the heterotetrameric AGP
      holoenzyme, is primarily under transcriptional control during tuber development.
      In contrast, noncoordinate expression of the subunit transcripts was evident in
      leaves in which the relative level of the sAGP mRNA was present at severalfold
      excess compared to the level of IAGP mRNA. Immunoblot analysis, however, revealed
      that the levels of sAGP and IAGP polypeptides were present at near equimolar
      amounts, indicating that a posttranscriptional event co-ordinates subunit
      polypeptide levels. This posttranscriptional control of subunit abundance was
      also evident in leaves subjected to a photoperiod regime and during sucrose
      induced starch synthesis. The predominant role of transcriptional and
      posttranscriptional regulation of AGP in tubers and leaves, respectively, is
      consistent with the distinct pathways of carbon partitioning and with the type
      and function of starch synthesis that occurs within each tissue.

PMID- 12228482
TI  - Leaf Epicuticular Waxes of the Eceriferum Mutants in Arabidopsis.
AB  - Wild-type Arabidopsis leaf epicuticular wax (EW) occurs as a smooth layer over
      the epidermal surface, whereas stem EW has a crystalline microstructure. Wild
      type EW load was more than 10-fold lower on leaves than on stems. Compared with
      the EW on wild-type stems, EW on wild-type leaves had a much higher proportion of
      their total EW load in the form of alkanes and 1-alcohols; a large reduction in
      secondary alcohols, ketones, and esters; and a chain-length distribution for
      major EW classes that was skewed toward longer lengths. The eceriferum (cer)
      mutations often differentially affected leaf and stem EW chemical compositions.
      For example, the cer2 mutant EW phenotype was expressed on the stem but not on
      the leaf. Compared to wild type, the amount of primary alcohols on cer9 mutants
      was reduced on leaves but elevated on stems, whereas an opposite differential
      effect for primary alcohols was observed on cer16 leaves and stems. Putative
      functions for CER gene products are discussed. The CER4 and CER6 gene products
      may be involved in fatty aldehyde reduction and C26 fatty acylcoenzyme A
      elongation, respectively. CER1, CER8, CER9, and CER16 gene products may be
      involved in EW substrate transfer. The CER3 gene product may be involved in
      release of fatty acids from elongase complexes. CER2 gene product may have
      regulatory functions.

PMID- 12228483
TI  - Characterization of the Red Beet Plasma Membrane H+-ATPase Reconstituted in a
      Planar Bilayer System.
AB  - The transport activity of the red beet (Beta vulgaris L.) plasma membrane H+
      ATPase was examined following reconstitution into a planar bilayer membrane.
      Fusion of partially purified plasma membrane H+-ATPase with the bilayer membrane
      was accomplished by perfusion of proteoliposomes against the bilayer under
      hypoosmotic conditions. Following incorporation into the bilayer, an ATP
      dependent current was measured that demonstrated properties consistent with those
      of the plasma membrane H+-ATPase. Current production was substrate specific for
      ATP, inhibited by orthovanadate, and insensitive to 200 nM erythrosin B but
      inhibited by 100 [mu]M erythrosin B. When current production was measured as a
      function of Mg:ATP concentration, a simple Michaelis-Menten relationship was
      observed and a Km of 0.62 mM was estimated. Current-voltage analysis of ATP
      dependent current in the presence of 0.5 mM ATP, 20 mM ADP, 40 mM orthophosphate,
      and an opposing 2.5-unit [delta]pH revealed a reversal potential of about -149
      mV. Based on the free energy available from ATP hydrolysis, this reversal
      potential is consistent with an H+/ATP stoichiometry of 1. This study
      demonstrates the usefulness of a planar bilayer system for investigation of
      energy coupling to H+ transport by the plasma membrane H+-ATPase.

PMID- 12228484
TI  - The Compartmentation of Acetyl-Coenzyme A Carboxylase in Plants.

PMID- 12228485
TI  - Mitochondria Increase Three-Fold and Mitochondrial Proteins and Lipid Change
      Dramatically in Postmeristematic Cells in Young Wheat Leaves Grown in Elevated
      CO2.
AB  - A dramatic stimulation in mitochondrial biogenesis during the very early stages
      of leaf development was observed in young wheat plants (Triticum aestivum cv
      Hereward) grown in elevated CO2 (650 [mu]L L-1). An almost 3-fold increase in the
      number of mitochondria was observed in the very young leaf cells at the base of
      the first leaf of a 7-d-old wheat plant. In the same cells large increases in the
      accumulation of a mitochondrial chaperonin protein and the mitochondrial 2
      oxoglutarate dehydrogenase complex and pyruvate dehydrogenase complex were
      detected by immunolabeling. Furthermore, the basal segment also shows a large
      increase in the rate of radiolabeling of diphosphatidylglycerol, a lipid confined
      to the inner mitochondrial membrane. This dramatic response in very young leaf
      cells to elevated CO2 suggests that the numerous documented positive effects of
      elevated CO2 on wheat leaf development are initiated as early as 12 h
      postmitosis.

PMID- 12228486
TI  - In Situ Detection of nDNA Fragmentation during the Differentiation of Tracheary
      Elements in Higher Plants.
AB  - Programmed cell death (pcd) is thought to occur during the autolysis of xylem
      vessels. Although several ultrastructural aspects of this differentiation process
      have been characterized, certain key aspects of this process remain unsolved.
      Here we demonstrate in pea (Pisum sativum) that nuclei of vessel elements
      undergoing pcd contain fragmented nDNA. This finding may provide evidence for the
      activation of a DNA degradation mechanism prior to the final disruption of the
      nucleus that occurs during the autolysis stage of this differentiation process.
      In situ detection of DNA fragmentation in nuclei of vessel elements undergoing
      pcd may therefore suggest that this death process involves the activation of a
      mechanism for DNA degradation, similar to that activated during apoptosis in
      animal cells. In addition, this differentiation process may serve as a useful
      positive control for the in situ detection of pcd in other developmental pathways
      and during the hypersensitive response of plants to avirulent pathogens.

PMID- 12228487
TI  - Phenotypic Suppression of the Gibberellin-Insensitive Mutant (gai) of
      Arabidopsis.
AB  - The semidominant gibberellin-insensitive (gai) mutant of Arabidopsis thaliana
      shows impairment in multiple responses to the plant hormone gibberellin A3, which
      include effects on seed germination, stem elongation, apical dominance, and rapid
      flowering in short days. Results presented here show that the gai mutation also
      interferes with development of fertile flowers in continuous light. Mu-tagenesis
      of the gai mutant resulted in recovery of 17 independent mutants in which the
      gibberellin-insensitive phenotype is partially or completely suppressed. Sixteen
      of the suppressor mutations act semidominantly to restore gibberellin
      responsiveness. One representative of this class, the gar1 mutation, could not be
      genetically separated from the gai locus and is proposed to cause inactivation of
      the gai gene. The exceptional gar2 mutation partially suppresses the gai
      phenotype, is completely dominant, and is not linked to the gai locus. The gar2
      mutation may define a new gene involved in gibberellin signaling. A recessive
      allele of the spindly (SPY) locus, spy-5, was also found to partially suppress
      the gai mutant phenotype.

PMID- 12228488
TI  - Hrp Mutant of Pseudomonas syringae pv phaseolicola Induces Cell Wall Alterations
      but Not Membrane Damage Leading to the Hypersensitive Reaction in Lettuce.
AB  - Both wild-type (S21-WT) and hrpD- (S21-533) strains of Pseudomonas syringae pv
      phaseolicola induced the formation of large paramural papillae in lettuce
      (Lactuca sativa) mesophyll cells adjacent to bacterial colonies. Localized
      alterations to the plant cell wall included deposition of hydroxyproline-rich
      glycoproteins, phe-nolics, and callose, and were associated with proliferation of
      the endoplasmic reticulum and multivesicular bodies. Tissue collapse during the
      hypersensitive reaction caused by S21-WT was associated with electrolyte leakage
      and rapid accumulation of the phy-toalexin lettucenin A, both of which followed
      membrane damage indicated by the failure of mesophyll cells to plasmolyze. A few
      cells lost the ability to plasmolyze after inoculation with S21-533, and low
      levels of lettucenin A were recorded, but neither leakage of electrolytes nor
      tissue collapse were detected. Dysfunction of the plasma membrane in cells
      adjacent to colonies of S21-WT led to extensive vacuolation of the cytoplasm,
      organelle disruption, and cytoplasmic collapse[mdash]changes unlike those
      occurring in cells undergoing apoptosis. Strain S21-533 remained viable within
      symptomless tissue, whereas cells of S21-WT were killed as a consequence of the
      hypersensitive reaction. Our observations emphasize the subtle coordination of
      the plant's response occurring at the subcellular level.

PMID- 12228489
TI  - Effect of the Growth Retardant 3,5-Dioxo-4-butyryl-cyclohexane Carboxylic Acid
      Ethyl Ester, an Acylcyclohexanedione Compound, on Fruit Growth and Gibberellin
      Content of Pollinated and Unpollinated Ovaries in Pea.
AB  - Treatment of pollinated pea (Pisum sativum L. cv Alaska, line V1) ovaries with
      3,5-dioxo-4-butyryl-cyclohexane carboxylic acid ethyl ester (LAB), an
      acylcyclohexanedione derivative that competitively inhibits 2-oxoglutarate
      dependent gibberellin (GA) dioxygenases, caused a reduction of pod elongation
      proportional to the amount of inhibitor applied. The effect of LAB was
      counteracted by GA1 and GA3, and partially by GA20. The inhibitor decreased the
      contents of GA1 and GA3 (the purported active GAs) and GA8, increased those of
      GA19 and GA20, and did not affect that of GA29 in both the pod and the developing
      seeds. These results provide evidence that GA1 and/or GA3 control pod development
      in pea and show that GA20 is not active per se. In contrast to its effect on
      pollinated ovaries, LAB promoted parthenocarpic development of unpollinated
      ovaries, which is associated with an increase of GA1 and GA8 content. The
      inhibitor enhanced the response of unpollinated ovaries to GA1 and GA20, but it
      did not alter the response to GA3. LAB is proposed to promote parthenocarpic
      development and enhance the response to exogenous GAs by blocking the 2[beta]
      hydroxylation of GA1 more efficiently than 3[beta]-hydroxylation of GA20.

PMID- 12228490
TI  - New lv Mutants of Pea Are Deficient in Phytochrome B.
AB  - The lv-1 mutant of pea (Pisum sativum L.) is deficient in responses regulated by
      phytochrome B (phyB) in other species but has normal levels of spectrally active
      phyB. We have characterized three further lv mutants (lv-2, lv-3, and lv-4),
      which are all elongated under red (R) and white light but are indistinguishable
      from wild type under far-red light. The phyB apoprotein present in the lv-1
      mutant was undetectable in all three new lv mutants. The identification of
      allelic mutants with and without phyB apoprotein suggests that Lv may be a
      structural gene for a B-type phytochrome. Furthermore, it indicates that the lv-1
      mutation results specifically in the loss of normal biological activity of this
      phytochrome. Red-light-pulse and fluence-rate-response experiments suggest that
      lv plants are deficient in the low-fluence response (LFR) but retain a normal
      very-low-fluence-rate-dependent response for leaflet expansion and inhibition of
      stem elongation. Comparison of lv alleles of differing severity indicates that
      the LFR for stem elongation can be mediated by a lower level of phyB than the LFR
      for leaflet expansion. The retention of a strong response to continuous low
      fluence-rate R in all four lv mutants suggests that there may be an additional
      phytochrome controlling responses to R in pea. The kinetics of phytochrome
      destruction and reaccumulation in the lv mutant indicate that phyB may be
      involved in the light regulation of phyA levels.

PMID- 12228491
TI  - Alfalfa Root Flavonoid Production Is Nitrogen Regulated.
AB  - Flavonoids produced by legume roots are signal molecules acting both as
      chemoattractants and nod gene inducers for the symbiotic Rhizobium partner.
      Combined nitrogen inhibits the establishment of the symbiosis. To know whether
      nitrogen nutrition could act at the level of signal production, we have studied
      the expression of flavonoid biosynthetic genes as well as the production of
      flavonoids in the roots of plants grown under nitrogen-limiting or nonlimiting
      conditions. We show here that growth of the plant under nitrogen-limiting
      conditions results in the enhancement of expression of the flavonoid biosynthesis
      genes chalcone synthase and isoflavone reductase and in an increase of root
      flavonoid and isoflavonoid production as well as in the Rhizobium meliloti nod
      gene-inducing activity of the root extract. These results indicate that in
      alfalfa (Medicago sativa L.) roots, the production of flavonoids can be
      influenced by the nitrogen nutrition of the plant.

PMID- 12228492
TI  - Calcium/Calmodulin Activation of Soybean Glutamate Decarboxylase.
AB  - Recently, we provided preliminary evidence for calcium (Ca2+)/calmodulin (CaM)
      stimulation of plant glutamate decarboxylase (GAD; EC 4.1.1.15). In the present
      study, a detailed characterization of the phenomenon is described. GAD was
      partially purified from various soybean (Glycine max L. Merr.) tissues
      (developing seed coat and cotyledons, leaf, and root) in the presence of EDTA by
      a combination of ammonium sulfate precipitation and anion-exchange fast protein
      liquid chromatography. GAD activity showed a sharp optimum at pH 5.8, with about
      12% of maximal activity at pH 7. It was stimulated 2- to 8-fold (depending on the
      tissue source) in the presence of Ca2+/CaM at pH 7 but not at pH 5.8.
      Furthermore, when the protease inhibitor phenylmethylsulfonyl fluoride was
      omitted from the purification procedure, GAD activity was insensitive to Ca2+/CaM
      but was similar in magnitude to CaM-stimulated activity. The stimulation by
      Ca2+/CaM was fully inhibited by the CaM antagonists N-(6-aminohexyl)-5-chloro-1
      naphthalenesulfon-amide and trifluoperazine. With saturating CaM or Ca2+, the
      concentrations of Ca2+ and CaM required for half-maximal stimulation were about 7
      to 11 [mu]M and 25 nM, respectively. The effect of Ca2+ and CaM appeared to be
      through a 2.4-fold stimulation of Vmax and a 55% reduction in Km. The results
      suggested that GAD is activated via Ca2+ signal transduction.

PMID- 12228493
TI  - Induction of Lipid and Oleosin Biosynthesis by (+)-Abscisic Acid and Its
      Metabolites in Microspore-Derived Embryos of Brassica napus L.cv Reston
      (Biological Responses in the Presence of 8[prime]-Hydroxyabscisic Acid).
AB  - Microspore-derived (MD) embryos of Brassica napus L. cv Reston were used to test
      the effects of (+)-abscisic acid ([(+)-ABA]) and its metabolites, 8[prime]
      hydroxyabscisic acid (8[prime]-OH ABA) and (-)-phaseic acid (PA), on the
      accumulation of very long-chain monounsaturated fatty acids (VLCMFAs) and
      induction of genes encoding a 19-kD oleosin protein and a [delta]15 desaturase
      during embryogenesis. Developing early to mid-cotyledonary MD embryos at 16 to 19
      d in culture were treated with 10 [mu]M hormone/metabolite for 4 d. At various
      times during incubation, embryos and medium were analyzed to determine levels of
      hormone/metabolite, VLCMFAs, and oleosin or [delta]15 desaturase transcripts. The
      VLCMFAs, 20:1 and 22:1, primarily in triacylglycerols, increased by 200% after 72
      h in the presence of (+)-ABA and 8[prime]-OH ABA relative to the control. In
      contrast, treatment with PA for 72 h had little effect (20% increase) on the
      level of VLCMFAs. The first 24 to 72 h of (+)-ABA treatment were critical in the
      induction of VLCMFA biosynthesis, with 8[prime]-OH ABA lagging slightly behind
      (+)-ABA in promoting this response. The accumulation of VLCMFAs was positively
      correlated with an increase in elongase activity. (+)-ABA and its 8[prime]-OH ABA
      metabolite induced the accumulation of a 19-kD oleosin transcript within 2 to 4 h
      in culture. In addition, both (+)-ABA and 8[prime]-OH ABA induced the same level
      of [delta]15 desaturase transcript by 8 h. PA had no effect on the induction of
      either oleosin or [delta]15 desaturase transcripts. To our knowledge, this is the
      first report of the biological activity of 8[prime]-OH ABA and of stimulatory
      effects of (+)-ABA and 8[prime]-OH ABA on lipid and oleosin biosynthesis.

PMID- 12228494
TI  - Abscisic Acid Structure-Activity Relationships in Barley Aleurone Layers and
      Protoplasts (Biological Activity of Optically Active, Oxygenated Abscisic Acid
      Analogs).
AB  - Optically active forms of abscisic acid (ABA) and their oxygenated metabolites
      were tested for their biological activity by examining the effects of the
      compounds on the reversal of gibberellic acid-induced [alpha]-amylase activity in
      barley (Hordeum vulgare cv Himalaya) aleurone layers and the induction of gene
      expression in barley aleurone protoplasts transformed with a chimeric construct
      containing the promoter region of an albumin storage protein gene. Promotion of
      the albumin storage protein gene response had a more strict stereochemical
      requirement for elicitation of an ABA response than inhibition of [alpha]-amylase
      gene expression. The naturally occurring stereoisomer of ABA and its metabolites
      were more effective at eliciting an ABA-like response. ABA showed the highest
      activity, followed by 7[prime]-hydroxyABA, with phaseic acid being the least
      active. Racemic 8[prime]-hydroxy-2[prime],3[prime]-dihydroABA, an analog of
      8[prime]-hydroxyABA, was inactive, whereas racemic 2[prime],3[prime]-dihydroABA
      was as effective as ABA. The differences in response of the same tissue to the
      ABA enantiomers lead us to conclude that there exists more than one type of ABA
      receptor and/or multiple signal transduction pathways in barley aleurone tissue.

PMID- 12228495
TI  - Assay, Purification, and Partial Characterization of Choline Monooxygenase from
      Spinach.
AB  - The osmoprotectant glycine betaine is synthesized via the path-way choline ->
      betaine aldehyde -> glycine betaine. In spinach (Spinacia oleracea), the first
      step is catalyzed by choline monooxygenase (CMO), and the second is catalyzed by
      betaine aldehyde dehydrogenase. Because betaine aldehyde is unstable and not
      easily detected, we developed a coupled radiometric assay for CMO. [14C]Choline
      is used as substrate; NAD+ and betaine aldehyde dehydrogenase prepared from
      Escherichia coli are added to oxidize [14C]betaine aldehyde to [14C]glycine
      betaine, which is isolated by ion exchange. The assay was used in the
      purification of CMO from leaves of salinized spinach. The 10-step procedure
      included polyethylene glycol precipitation, polyethyleneimine precipitation,
      hydrophobic interaction, anion exchange on choline-Sepharose,
      dimethyldiethanolamine-Sepharose, and Mono Q, hydroxyapatite, gel filtration, and
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Following gel
      filtration, overall purification was about 600-fold and recovery of activity was
      0.5%. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed a
      polypeptide with a molecular mass of 45 kD. Taken with the value of 98 kD
      estimated for native CMO (R. Brouquisse, P. Weigel, D. Rhodes, C.F. Yocum, A.D.
      Hanson [1989] Plant Physiol 90: 322-329), this indicates that CMO is a homodimer.
      CMO preparations were red-brown, showed absorption maxima at 329 and 459 nm, and
      lost color upon dithionite addition, suggesting that CMO is an iron-sulfur
      protein.

PMID- 12228496
TI  - Nucleotide Levels Do Not Critically Determine Survival of Maize Root Tips
      Acclimated to a Low-Oxygen Environment.
AB  - We tested the hypothesis that ATP levels and energy charge determine the
      resistance of maize (Zea mays) root tips to anoxia. We focused on root tips of
      whole maize seedlings that had been acclimated to low O2 by exposure to an
      atmosphere of 3% (v/v) O2 in N2. Acclimated anoxic root tips characteristically
      have higher ATP levels and energy charge and survive longer under anoxia than
      nonacclimated tips. We poisoned intact, acclimated root tips with either fluoride
      or mannose, causing decreases in ATP and energy charge to values similar to or,
      in most cases, below those found in nonacclimated anoxic tips. With the exception
      of the highest fluoride concentration used, the poisoned, acclimated tips
      remained much more tolerant of anoxia than nonacclimated root tips. We conclude
      that high ATP and energy charge are not components critical for the survival of
      acclimated root tips during anoxia. The reduced nucleotide status in poisoned,
      acclimated root tips had little effect on cytoplasmic pH regulation during
      anoxia. This result indicates that in anoxic, acclimated root tips either
      cytoplasmic pH regulation is not dominated by ATP-dependent processes or these
      processes can continue in vivo largely independently of any changes in ATP levels
      in the physiological range. The role of glycolytic flux in survival under anoxia
      is discussed.

PMID- 12228497
TI  - Enzymatic Evidence for a Complete Oxidative Pentose Phosphate Pathway in
      Chloroplasts and an Incomplete Pathway in the Cytosol of Spinach Leaves.
AB  - The intracellular localization of transaldolase, transketolase, ribose-5
      phosphate isomerase, and ribulose-5-phosphate epimerase was reexamined in spinach
      (Spinacia oleracea L.) leaves. We found highly predominant if not exclusive
      localization of these enzyme activities in chloroplasts isolated by isopyknic
      centrifugation in sucrose gradients. Glucose-6-phosphate dehydrogenase, 6
      phosphogluconate dehydrogenase, glucose phosphate isomerase, and triose phosphate
      isomerase activity was present in the chloroplast fraction but showed additional
      activity in the cytosol (supernatant) fraction attributable to the cytosol
      specific isoforms known to exist for these enzymes. Anion-exchange chromatography
      of proteins of crude extracts on diethylaminoethyl-Fractogel revealed only a
      single enzyme each for transaldolase, transketolase, ribose-5-phosphate
      isomerase, and ribulose-5-phosphate epimerase. The data indicate that
      chloroplasts of spinach leaf cells possess the complete complement of enzymes of
      the oxidative pentose phosphate path-way (OPPP), whereas the cytosol contains
      only the first two reactions, contrary to the widely held view that plants
      generally possess a cytosolic OPPP capable of cyclic function. The chloroplast
      enzymes transketolase, ribose-5-phosphate isomerase, and ribulose-5-phosphate
      epimerase appear to be amphibolic for the Calvin cycle and OPPP.

PMID- 12228498
TI  - Vernalization and Gibberellin Physiology of Winter Canola (Endogenous Gibberellin
      (GA) Content and Metabolism of [3H]GA1 and [3H]GA20.
AB  - Winter canola (Brassica napus cv Crystal) is an oilseed crop that requires
      vernalization (chilling treatment) for the induction of stem elongation and
      flowering. To investigate the role of gibberellins (GAs) in vernalization-induced
      events, endogenous GA content and the metabolism of [3H]GAs were examined in 10
      week vernalized and nonvernalized plants. Shoot tips were harvested 0, 8, and 18
      d postvernalization (DPV), and GAs were purified and quantified using 2H2
      internal standards and gas chromatography-selected ion monitoring. Concentrations
      of GA1, GA3, GA8, GA19, and GA20 were 3.1-, 2.3-, 7.8-, 12.0-, and 24.5-fold
      higher, respectively, in the vernalized plants at the end of the vernalization
      treatment (0 DPV) relative to the nonvernalized plants. Thermoregulation
      apparently occurs prior to GA19 biosynthesis, since vernalization elevated the
      concentration of all of the monitored GAs. [3H]GA20 or [3H]GA1 was applied to the
      shoot tips of vernalized and nonvernalized plants, and after 24 h, plants were
      harvested at 6, 12, and 15 DPV. Following high-performance liquid chromatography
      analyses, vernalized plants showed increased conversion of [3H]GA20 to a [3H]GA1
      like metabolite and reduced conversion of [3H]GA1 or [3H]GA20 to polar 3H
      metabolites, putative glucosyl conjugates. These results demonstrate that
      vernalization influences GA content and GA metabolism, with GAs serving as
      probable regulatory intermediaries between chilling treatment and subsequent stem
      growth.

PMID- 12228499
TI  - The Physiological Role of Abscisic Acid in Eliciting Turion Morphogenesis.
AB  - The exogenous application of hormones has led to their implication in a number of
      processes within the plant. However, proof of their function in vivo depends on
      quantitative data demonstrating that the exogenous concentration used to elicit a
      response leads to tissue hormone levels within the physiological range. Such
      proof is often lacking in many investigations. We are using abscisic acid (ABA)
      induced turion formation in Spirodela polyrrhiza L. to investigate the mechanism
      by which a hormone can trigger a morphogenic switch. In this paper, we
      demonstrate that the exogenous concentration of ABA used to induce turions leads
      to tissue concentrations of ABA within the physiological range, as quantified by
      both enzyme-linked immunosorbent assay and high-performance liquid
      chromatography/gas chromatography-electron capture detection analysis. These
      results are consistent with ABA having a physiological role in turion formation,
      and they provide an estimate of the changes in endogenous ABA concentration
      required if environmental effectors of turion formation (e.g. nitrate deficiency,
      cold) act via an increased level of ABA. In addition, we show that the (+)- and (
      )-enantiomers of ABA are equally effective in inducing turions. Moreover,
      comparison of the ABA; levels attained after treatment with (+)-, (-)-, and
      ([plus or minus])-ABA and their effect on turion induction and comparison of the
      effectiveness of ABA on turion induction under different pH regimes suggest that
      ABA most likely interacts with a plasmalemma-located receptor system to induce
      turion formation.

PMID- 12228500
TI  - Salicylic Acid in Rice (Biosynthesis, Conjugation, and Possible Role).
AB  - Salicylic acid (SA) is a natural inducer of disease resistance in some
      dicotyledonous plants. Rice seedlings (Oryza sativa L.) had the highest levels of
      SA among all plants tested for SA content (between 0.01 and 37.19 [mu]g/g fresh
      weight). The second leaf of rice seedlings had slightly lower SA levels than any
      younger leaves. To investigate the role of SA in rice disease resistance, we
      examined the levels of SA in rice (cv M-201) after inoculation with bacterial and
      fungal pathogens. SA levels did not increase after inoculation with either the
      avirulent pathogen Pseudomonas syringae D20 or with the rice pathogens
      Magnaporthe grisea, the causal agent of rice blast, and Rhizoctonia solani, the
      causal agent of sheath blight. However, leaf SA levels in 28 rice varieties
      showed a correlation with generalized blast resistance, indicating that SA may
      play a role as a constitutive defense compound. Biosynthesis and metabolism of SA
      in rice was studied and compared to that of tobacco. Rice shoots converted
      [14C]cinnamic acid to SA and the lignin precursors p-coumaric and ferulic acids,
      whereas [14C]benzoic acid was readily converted to SA. The data suggest that in
      rice, as in tobacco, SA is synthesized from cinnamic acid via benzoic acid. In
      rice shoots, SA is largely present as a free acid; however, exogenously supplied
      SA was converted to [beta]-O-D-glucosylSA by an SA-inducible glucosyltransferase
      (SA-GTase). A 7-fold induction of SA-GTase activity was observed after 6 h of
      feeding 1 mM SA. Both rice roots and shoots showed similar patterns of SA-GTase
      induction by SA, with maximal induction after feeding with 1 mM SA.

PMID- 12228501
TI  - Characterization and Physiological Function of Class I Low-Molecular-Mass, Heat
      Shock Protein Complex in Soybean.
AB  - Examination of an ammonium sulfate-enriched fraction (70-100% saturation) of heat
      shock proteins (HSPs) by nondenaturing polyacrylamide gel electrophoresis
      revealed the presence of a high molecular mass complex (280 kD) in soybean
      (Glycine max) seedlings. This complex cross-reacted with antibodies raised
      against soybean class I low-molecular-mass (LMW) HSPs. Dissociation of the
      complex by denaturing polyacrylamide gel electrophoresis showed the complex to
      contain at least 15 polypeptides of the 15-to 18-kD class I LMW HSPs that could
      be detected by staining, radiolabeling, and western blotting. A similar LMW-HSP
      complex was observed in mung bean (Vigna radiata L.; 295 kD), in pea (Pisum
      sativum L.; 270 kD), and in rice (Oryza sativa L.; 310 kD). The complex was
      stable under high salt conditions (250 mM KCI), and the integrity was not
      affected by 1% Nonidet P-40 and 3 [mu]g/ML RNase treatment. The size of the
      isolated HSP complex in vitro was conserved to 55[deg]C; however, starting at
      37.5[deg]C, it changed to higher molecular forms in the presence of soluble
      proteins. The isolated HSP complex was able to protect up to 75% of the soluble
      proteins from heat denaturation in vitro.

PMID- 12228502
TI  - Mutations Affecting O-Glycosylation in Chlamydomonas reinhardtii Cause Delayed
      Cell Wall Degradation and Sex-Limited Sterility.
AB  - We describe a mutation, gag-1, that affects in a temperature-dependent manner a
      specific type of O-glycosylation in the green alga Chlamydomonas reinhardtii. In
      the mutant, all the major glycoproteins, in particular cell wall proteins, show a
      decreased apparent molecular weight in polyacrylamide gels, and their
      antigenicity is affected. The mutant forms multicellular aggregates (palmelloid
      colonies) at the restrictive temperature due to the delayed release of the
      daughter cells from the mother cell wall after mitosis. In addition, the mutation
      causes sterility by preventing sexual agglutination. In contrast to the other
      phenotypes, the sterility phenotype is temperature independent, and it is
      expressed only by cells of the plus mating type. We show that imp-8, a previously
      described nonagglutinating sex-limited mutation, causes the same glycosylation
      defect and is allelic to gag-1. Thus, expression of mt+ agglutinability appears
      to require the specific type of O-glycosylation that is defective in these
      mutants. More generally, these observations show that a sex-limited phenotype can
      be caused by a mutation in a gene that is not itself sex limited in its
      expression.

PMID- 12228503
TI  - Expression of Phospholipase D during Castor Bean Leaf Senescence.
AB  - Membrane deterioration in plant senescence is commonly associated with
      progressive decreases in membrane phospholipid content. This study investigated
      the expression and regulation of phospholipase D (PLD; EC 3.1.4.4) during
      senescence in castor bean (Ricinus communis L. cv Hale) leaf discs. The rate of
      leaf senescence was accelerated by 50 [mu]M abscisic acid and was attenuated by
      50 [mu]M cytokinin during incubation at 23[deg]C for up to 5 d. Leaf senescence
      was indicated by decreases in the content of total proteins, chlorophyll, and
      phospholipids. PLD activity in both membrane-associated and cytosolic fractions
      showed a gradual increase in the absence of phytohormones. Abscisic acid
      stimulated an increase in membrane-associated PLD and had little effect on the
      soluble form. On the other hand, cytokinin retarded the increase in membrane
      associated PLD. Immunoblotting analysis using PLD-specific antibodies revealed
      that the changes in PLD activity were correlated with those of PLD protein.
      Analysis of PLD by nondenaturing PAGE showed the appearance of a PLD structural
      variant, PLD 3, in abscisic acid-treated leaf discs. Northern blotting analysis
      using a PLD cDNA probe revealed an increase in PLD mRNA in senescing leaf discs.
      These data indicate complex mechanisms for the regulation of PLD during
      senescence, which include increases in membrane-associated PLD, differential
      expression of PLD isoforms, and changes in amounts of PLD protein and mRNA. Such
      controlled expression points to a role for PLD in membrane deterioration and
      plant senescence.

PMID- 12228504
TI  - An Investigation of the Sustained Component of Nonphotochemical Quenching of
      Chlorophyll Fluorescence in Isolated Chloroplasts and Leaves of Spinach.
AB  - The slowly reversible component of nonphotochemical quenching of Chl
      fluorescence, ql, has been investigated in intact leaves and chloroplasts of
      spinach (Spinacia oleracea). In leaves, between 50 and 100% of ql (defined as the
      quenching that remained after at least 10 min of dark adaptation of a previously
      illuminated leaf) is instantly reversible when leaves were infiltrated with
      nigericin. Chloroplasts isolated from leaves in which ql had been induced by
      prior illumination retained the same level of quenching. No pH gradient, as
      measured by quenching of 9-aminoacridine fluorescence, was present. However,
      addition of nigericin caused a partial removal of ql, as observed in whole
      leaves. It is concluded that ql is not related to a persistence of a bulk phase
      pH gradient in darkness but to a structural change in the thylakoid that can be
      reversed by addition of nigericin. The relationship between these observations
      and the hypothesis that nonphotochemical quenching of chlorophyll fluorescence
      results from protonation of light-harvesting complex of photosystem II components
      is discussed.

PMID- 12228505
TI  - Effect of Anoxia on Carbohydrate Metabolism in Rice Seedlings.
AB  - The metabolism of carbohydrates was investigated in rice (Oryza sativa L.)
      seedlings grown under anoxia. Two phases can be recognized in the utilization of
      carbohydrates: during the first days of germination under anoxia, the metabolism
      of sugars is mainly degradative, whereas after the induction of [alpha]-amylase
      (EC 3.2.1.1) has taken place, the increased presence of glucose and sucrose
      indicates that both starch degradation and sucrose synthesis operate. The
      analysis of the enzymes involved in carbohydrate metabolism indicates that anoxic
      rice seedlings possess a set of enzymes that allow the efficient metabolism of
      starch and sucrose to fructose-6-phosphate. We propose that cytosolic sucrose
      metabolism in anoxic rice seedlings takes place mainly through a sucrose synthase
      (EC 2.4.1.13) pathway with nucleoside diphosphate kinase (EC 2.7.4.6), allowing
      the cycling of urydilates needed for the operation of this pathway.

PMID- 12228506
TI  - Simultaneous Measurement of Intracellular pH and K+ or NO3- in Barley Root Cells
      Using Triple-Barreled, Ion-Selective Microelectrodes.
AB  - The manufacture and use of triple-barreled microelectrodes, which are capable of
      simultaneous in vivo measurement of intracellular pH and the activities of K+ or
      NO3- and cell membrane potential (Em), are described. Scanning electron
      micrographs showed that the three tips were aligned and that the overall tip
      diameter was approximately 0.8 [mu]m. When filled with 100 mM KCl, all three
      barrels simultaneously reported identical transmembrane potentials, showing that
      all three tips were located in the same subcellular compartment. Intracellular
      estimates of Em in barley (Hordeum vulgare L. cv Klaxon) root epidermal cells
      obtained with these triple-barreled microelectrodes were indistinguishable from
      those obtained using single- or double-barreled microelectrodes. Measurements
      made with triple-barreled K+ and pH-selective microelectrodes in root cells of 7
      d-old barley plants grown in a nutrient solution containing 0.5 mM K+ yielded
      cytosolic and vacuolar populations having mean K+ activity values of 71.3 and
      68.7 mM, respectively. The associated mean pH values ([plus or minus]SE) were
      7.26 [plus or minus] 0.06 (cytosol) and 5.18 [plus or minus] 0.08 (vacuole).
      Analysis of whole-tissue digests confirmed the microelectrode measurements.
      Measurements made using triple-barreled pH- and nitrate-selective microelectrodes
      confirmed earlier double-barreled measurements of pH and nitrate in barley root
      epidermal cells growing in 10 mM nitrate.

PMID- 12228507
TI  - Antioxidant Defenses against Activated Oxygen in Pea Nodules Subjected to Water
      Stress.
AB  - The involvement of activated oxygen in the drought-induced damage of pea (Pisum
      sativum L. cv Frilene) nodules was examined. To this purpose, various pro-oxidant
      factors, antioxidant enzymes and related metabolites, and markers of oxidative
      damage were determined in nodules of well-watered (nodule water potential
      approximately -0.29 MPa) and water-stressed (nodule water potential approximately
      -2.03 MPa) plants. Water-stressed nodules entered senescence as evidenced by the
      30% decrease in leghemoglobin and total soluble protein. Drought also caused a
      decrease in the activities of catalase (25%), ascorbate peroxidase (18%),
      dehydroascorbate reductase (15%), glutathione reductase (31%), and superoxide
      dismutase (30%), and in the contents of ascorbate (59%), reduced (57%) and
      oxidized (38%) glutathione, NAD+ and NADH (43%), NADP+ (31%), and NADPH (17%).
      The decline in the antioxidant capacity of nodules may result from a restricted
      supply of NAD(P)H in vivo for the ascorbate-glutathione pathway and from the Fe
      catalyzed Fenton reactions of ascorbate and glutathione with activated oxygen.
      The 2-fold increase in the content of "catalytic Fe" would also explain the
      augmented levels of lipid peroxides (2.4-fold) and oxidatively modified proteins
      (1.4-fold) found in water-stressed nodules because of the known requirement of
      lipid and protein oxidation for a transition catalytic metal.

PMID- 12228508
TI  - Factors Associated with Depression of Photosynthetic Quantum Efficiency in Maize
      at Low Growth Temperature.
AB  - The photosynthetic productivity of maize (Zea mays) in temperate regions is often
      limited by low temperatures. The factors responsible for the sensitivity of
      photosynthesis in maize to growth at suboptimal temperature were investigated by
      measuring (a) the quantum yields of CO2 fixation and photosystem II (PSII)
      photochemistry, (b) the pigments of the xanthophyll cycle, (c) the concentrations
      of active and inactive PSII reaction centers, and (d) the synthesis of core
      components of PSII reaction centers. Measurements were made on fully expanded
      leaves grown at 14[deg]C, both before and during the first 48 h after transfer of
      these plants to 25[deg]C. Our findings indicate that zeaxanthin-related quenching
      of absorbed excitation energy at PSII is, quantitatively, the most important
      factor determining the depressed photosynthetic efficiency in 14[deg]C-grown
      plants. Despite the photoprotection afforded by zeaxanthin-related quenching of
      absorbed excitation energy, a significant and more persistent depression of
      photosynthetic efficiency appears to result from low temperature-induced
      inhibition of the rate at which damaged PSII centers can be replaced.

PMID- 12228509
TI  - Hormonal Regulation of Organic and Phosphoric Acid Release by Barley Aleurone
      Layers and Scutella.
AB  - The release of acid from the aleurone layer and scutellum of barley (Hordeum
      vulgare L. cv Himalaya) was investigated. Aleurone layers isolated from mature
      barley grains acidify the external medium by releasing organic and phosphoric
      acids. Gibberellic acid and abscisic acid stimulate acid release 2-fold over
      control tissue incubated in 10 mM CACl2. Gibberellic acid causes medium
      acidification by stimulating the release of phosphoric and citric acids, whereas
      abscisic acid stimulates the release of malic acid. The accumulation of these
      acids in the incubation medium buffers the medium against changes in pH,
      particularly between pH 4 and 5. The amounts of amino acids that accumulate in
      the medium are low (2-12 nmol/layer) compared to other organic and phosphoric
      acids (100-500 nmol/layer). The scutellum does not play a major role in medium
      acidification but participates in the uptake of organic acids. The organic acid
      composition of the starchy endosperm changes after 3 d of imbibition; malic,
      succinic, and lactic acids decrease, whereas citric and phosphoric acids remain
      unchanged or increase. These results indicate that during postgerminative growth,
      the acidity of the starchy endosperm is maintained by acid production by the
      aleurone layer.

PMID- 12228510
TI  - Ozone-Induced Alterations in the Accumulation of Newly Synthesized Proteins in
      Leaves of Maize.
AB  - We examined the response of leaves of 3-week-old maize (Zea mays L.) to short
      term (5 h) fumigation with O3-enriched air (0, 0.12, 0.24, or 0.36 [mu]L/L).
      Older leaves and leaf tissue developed more severe visible damage at higher
      external O3 concentrations. To investigate the immediate effect of O3 exposure on
      the accumulation of newly synthesized leaf proteins, leaves were labeled with
      [35S]methionine after 2 h and fumigated for an additional 3 h. O3-induced
      alterations of leaf proteins were observed in a concentration-dependent manner.
      There was a significant decrease in [35S]methionine incorporation into protein at
      the highest O3 concentration. Developmental differences in accumulation of de
      novo-synthesized leaf proteins were observed when the leaf tip, middle, and basal
      sections were labeled under 0 [mu]L/L O3, and additional changes were apparent
      upon exposure to increasing O3 concentrations. Changes in leaf protein synthesis
      were observed in the absence of visible leaf injury. Subcellular fractionation
      revealed O3-induced alterations in soluble and membrane-associated proteins. A
      number of thylakoid membrane-associated proteins showed specific increases in
      response to O3 fumigation. In contrast, the synthesis of a 32-kD polypeptide
      associated with thylakoid membranes was reduced in response to O3 fumigation in
      parallel with reduced incorporation of [35S]methionine into protein.
      Immunoprecipitation identified this polypeptide as the D1 protein of photosystem
      II. A reduction in the accumulation of newly synthesized D1 could have
      consequences for the efficiency of photosynthesis and other cellular processes.

PMID- 12228511
TI  - Expression of a Low-Temperature-Induced Protein in Brassica napus.
AB  - BN28 is a low-temperature-induced, boiling-soluble protein in Brassica napus. We
      used antibodies raised against a recombinant BN28 to examine the expression of
      this protein in cold-acclimating plants and to investigate its relationship to
      plant freezing tolerance. Changes in the steady-state levels of BN28 protein
      appear to lag several days behind those of the mRNA. BN28 is first detected on
      immunoblots after approximately 8 d of exposure to low temperature, and
      thereafter levels remain stable while plants are maintained at 4[deg]C.
      Radiolabeling studies indicate that BN28 is synthesized at a relatively low rate.
      A decline in protein levels is observed soon after returning plants to control
      temperatures, and little or no protein can be detected after 7 d of
      deacclimation. The disappearance of the protein precedes a loss in freezing
      tolerance, suggesting that BN28 is not involved in maintaining plasma membrane
      integrity. Expression of BN28 is observed primarily in leaves and appears to be
      low-temperature specific. Quantitative analysis indicated that BN28 accumulates
      to approximately 82.7 pmol mg-1 total protein in cold-acclimated leaves. This
      concentration is similar to that reported for two group 2 late-embryogenesis
      abundant-like proteins.

PMID- 12228513
TI  - Plant Physiology: Three Years into a New Era.

PMID- 12228514
TI  - Cyclic AMP as a Second Messenger in Higher Plants (Status and Future Prospects).

PMID- 12228512
TI  - Evidence for Two Catalytic Sites in the Functional Unit of H+-ATPase from Higher
      Plants.
AB  - We investigated the nature of the complex ATP activation kinetics of plant H+
      ATPases. To this aim we analyzed that activation in three isolated isoforms
      (AHA1, AHA2, and AHA3) of H+-ATPase from Arabidopsis thaliana. The isoforms were
      obtained by heterologous expression in endoplasmic reticulum of yeast. ATP
      stimulation was always with low affinity (K0.5 between 500 and 1800 [mu]M). In
      addition, the curves were not Michaelian and displayed positive cooperativity.
      Detailed studies with AHA2 showed that (a) enzyme solubilized with
      lysophosphatidylcholine exhibited Michaelian behavior even in the presence of
      soybean lecithin liposomes free of enzyme, (b) solubilized enzyme incorporated
      into the same liposomes displayed two-site kinetics with negative cooperativity,
      and (c) enzyme partially digested with trypsin lost the C-terminal portion of the
      molecule. Under this condition the ATP activation kinetics was Michaelian or had
      a slight negative cooperativity and the K0.5ATP was reduced 3-fold. These data
      suggest that the functional unit of the H+-ATPase has two catalytic ATP sites
      with variable cooperativity and kinetics competence of the E(ATP) and E(ATP)2
      complexes. Such variability is likely modulated by the association of the enzyme
      with membrane structures and by a regulatory domain in the C terminus of the
      enzyme molecule.

PMID- 12228515
TI  - Aluminum Induces Rigor within the Actin Network of Soybean Cells.
AB  - Aluminum is toxic to both plants and animals. Root growth and pollen-tube
      extension are inhibited after aluminum stress in acidic environments. Incubation
      of cultured neurons with aluminum results in the formation of neurofibrillar
      tangles reminiscent of the neural pathology observed in Alzheimer's disease. The
      present communication demonstrates that aluminum induces a rapid and dramatic
      increase in the rigidity of the actin network in soybean (Glycine max) root
      cells. This rigidity can be prevented by either co-incubation with sodium
      fluoride or magnesium, or pretreatment with cytochalasin D. It is proposed that
      the growth-inhibitory activity and cytotoxicity of aluminum in plants may be a
      consequence of a global rigor that is induced within the actin network. This
      rigor may result from the formation of nonhydrolyzable [Al3+-ADP] or [Al3+-ATP]
      complexes whose binding to actin/myosin can modify contraction. Additionally,
      Al3+-mediated interference with the normal kinetics of F-actin filament
      assembly/disassembly could precipitate subsequent disorganization of associated
      cytoskeletal structures and promote altered expression of cytoskeletal proteins.

PMID- 12228516
TI  - Control of Vascular Sap pH by the Vessel-Associated Cells in Woody Species
      (Physiological and Immunological Studies).
AB  - In Robinia wood, the vessel-associated cells form a continuous sleeve around the
      vessels. Variations in pH of the solution perfused through the vessels during the
      annual cycle and the opposing effects of carbonyl cyanide-m-chlorophenylhydrazone
      and fusicoccin on this pH value indicate that some living cells of the wood are
      involved in the control of vascular sap pH and that this control fluctuates with
      the seasons. The immunolocalization of the plasma membrane HT+-ATPase in Robinia
      wood was studied by the immunogold-silver-staining technique using an antibody
      raised against a conserved stretch of the cytoplasmic domain of the H+-ATPase.
      The immunostaining is much stronger in vessel-associated cells than in other
      living cell types (ray and axial parenchyma elements) of the secondary xylem. Our
      data show an efficient involvement of this cell type in the control of vascular
      sap pH.

PMID- 12228517
TI  - A Temporarily Red Light-Insensitive Mutant of Tomato Lacks a Light-Stable, B-Like
      Phytochrome.
AB  - We have selected four recessive mutants in tomato (Lycopersicon esculentum Mill.)
      that, under continuous red light (R), have long hypocotyls and small cotyledons
      compared to wild type (WT), a phenotype typical of phytochrome B (phyB) mutants
      of other species. These mutants, which are allelic, are only insensitive to R
      during the first 2 days upon transition from darkness to R, and therefore we
      propose the gene symbol tri (temporarily red light insensitive). White light
      grown mutant plants have a more elongated growth habit than that of the WT. An
      immunochemically and spectrophotometrically detectable phyB-like polypeptide
      detectable in the WT is absent or below detection limits in the tri1 mutant. In
      contrast to the absence of an elongation growth response to far-red light (FR)
      given at the end of the daily photoperiod (EODFR) in all phyB-deficient mutants
      so far characterized, the tri1 mutant responds to EODFR treatment. The tri1
      mutant also shows a strong response to supplementary daytime far-red light. We
      propose that the phyB-like phytochrome deficient in the tri mutants plays a major
      role during de-etiolation and that other light-stable phytochromes can regulate
      the EODFR and shade-avoidance responses in tomato.

PMID- 12228518
TI  - Primary Metabolism in Plant Defense (Regulation of a Bean Malic Enzyme Gene
      Promoter in Transgenic Tobacco by Developmental and Environmental Cues).
AB  - NADP-dependent malic enzyme (NADP-ME, EC 1.1.1.40) catalyzes the oxidative
      decarboxylation of malate to pyruvate, producing CO2 and NADPH. We have examined
      regulatory properties of a 2.8-kb promoter-leader fragment of a bean (Phaseolus
      vulgaris L.) NADP-ME gene (PvME1) predicted to encode a cytosolic form of the
      enzyme by expression analysis of promoter-[beta]-glucuronidase fusions in
      transgenic tobacco plants. The PvME1 promoter directed strong expression in
      stems, which was confined to vascular and pith tissues, and was also active in
      floral and reproductive tissues. Wounding caused a marked induction of promoter
      activity, which was further strongly enhanced upon application of stimuli related
      to pathogen defense. Glutathione (reduced form) was the strongest inducer, but
      oxidized glutathione, fungal elicitor, cellulase, catalase, ascorbic acid, and
      NADPH were additional potent promoter-stimulating agents. Responsiveness to
      reduced glutathione was also shown at the level of PvME1 mRNA accumulation in
      bean plants. The putative contributions of NADP-ME gene expression to the plant
      defense response and possible mechanisms of defense gene regulation by conditions
      of oxidative stress as well as by H2O2 and antioxidant levels are discussed.

PMID- 12228519
TI  - Preincubation of Bradyrhizobium japonicum with Genistein Accelerates Nodule
      Development of Soybean at Suboptimal Root Zone Temperatures.
AB  - In the soybean (Glycine max [L.] Merr.) N2-fixing symbiosis, suboptimal root zone
      temperatures (RZTs) slow nodule development, especially at temperatures below
      17[deg]C. A step in the infection process that occurs within the first 24 h is
      particularly sensitive to suboptimal RZT. The first phase in the establishment of
      the soybean-Bradyrhizobium japonicum symbiosis is the exchange of recognition
      molecules. The most effective plant-to-bacterium signal is genistein. Binding of
      genistein to B. japonicum activates many of the B. japonicum nod genes. To our
      knowledge, the potential of sub-optimal RZT to disrupt this interorganismal
      signaling has not previously been investigated. Controlled environment
      experiments were conducted to determine whether the preincubation of B. japonicum
      with genistein increases soybean nodulation and N2 fixation at suboptimal RZT and
      whether the time between inoculation and root-hair curling is shortened by
      genistein application. The results of these experiments indicated that (a)
      genistein application increased soybean nodulation at suboptimal RZTs (17.5 and
      15[deg]C) but not at the optimal RZT (25[deg]C); (b) the period between
      inoculation and root-hair curling was shortened by inoculation with bradyrhizobia
      preincubated with genistein; (c) at 17.5 and 15[deg]C RZT, the onset of N2
      fixation occurred earlier in plants that received genistein-treated bradyrhizobia
      than in plants inoculated with untreated bradyrhizobia; (d) over the tested
      concentration range, genistein application at 15 to 20 [mu]M was the most
      effective in stimulating nodulation; and (e) between 25 and 15[deg]C, as RZT
      decreased, there was an increase in the nodulation-stimulating potential of
      genistein.

PMID- 12228520
TI  - Purification and Developmental Analysis of an Extracellular Proteinase from Young
      Leaves of Soybean.
AB  - A proteinase present in intercellular wash fluids from leaves of Glycine max has
      been purified 600-fold to electrophoretic homogeneity. The native protein is
      monomeric with a molecular mass of 60 kD, as estimated by denaturing gel
      electrophoresis, and has an isoelectric point of 7.7. The enzyme has a pH optimum
      of 9.5 when assayed with Azocoll as a substrate. The proteolytic activity is
      inhibited by p-chloromercuribenzoic acid and mercuric chloride and requires the
      presence of reducing agents. The enzyme activity is refractory to other classical
      sulfhydryl proteinases. The soybean leaf endoproteinase is present within the
      extracellular space of young leaves, and a portion is bound to the cell wall.
      Western blot analysis and activity measurements show that the enzyme is present
      only during the first 15 d postemergence of the leaf and is therefore under
      strict developmental control. We suggest that the enzyme may play a critical role
      in the extracellular milieu during rapid cell growth and leaf expansion.

PMID- 12228521
TI  - Increased Accumulation of Carbohydrates and Decreased Photosynthetic Gene
      Transcript Levels in Wheat Grown at an Elevated CO2 Concentration in the Field.
AB  - Repression of photosynthetic genes by increased soluble carbohydrate
      concentrations may explain acclimation of photosynthesis to elevated CO2
      concentration. This hypothesis was examined in a field crop of spring wheat
      (Triticum aestivum L.) grown at both ambient (approximately 360 [mu]mol mol-1)
      and elevated (550 [mu]mol mol-1) atmospheric CO2 concentrations using free-air
      CO2 enrichment at Maricopa, Arizona. The correspondence of steady-state levels of
      mRNA transcripts (coding for the 83-kD photosystem I apoprotein, sedoheptulose
      1,7-bisphosphatase, phosphoribulokinase, phosphoglycerokinase, and the large and
      small subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase) with leaf
      carbohydrate concentrations (glucose-6-phosphate, glucose, fructose, sucrose,
      fructans, and starch) was examined at different stages of crop and leaf
      development and through the diurnal cycle. Overall only a weak correspondence
      between increased soluble carbohydrate concentrations and decreased levels for
      nuclear gene transcripts was found. The difference in soluble carbohydrate
      concentration between leaves grown at elevated and current ambient CO2
      concentrations diminished with crop development, whereas the difference in
      transcript levels increased. In the flag leaf, soluble carbohydrate
      concentrations declined markedly with the onset of grain filling; yet transcript
      levels also declined. The results suggest that, whereas the hypothesis may hold
      well in model laboratory systems, many other factors modified its significance in
      this field wheat crop.

PMID- 12228522
TI  - Properties of a Maize Glutathione S-Transferase That Conjugates Coumaric Acid and
      Other Phenylpropanoids.
AB  - A glutathione S-transferase (GST) enzyme from corn (Zea mays L. Pioneer hybrid
      3906) that is active with p-coumaric acid and other unsaturated phenylpropanoids
      was purified approximately 97-fold and characterized. The native enzyme appeared
      to be a monomer with a molecular mass of approximately 30 kD and an apparent
      isoelectric point at pH 5.2. The enzyme had a pH optimum between 7.5 and 8.0 and
      apparent Km values of 4.4 and 1.9 mM for reduced glutathione (GSH) and p-coumaric
      acid, respectively. In addition to p-coumaric acid, the enzyme was also active
      with o-coumaric acid, m-coumaric acid, trans-cinnamic acid, ferulic acid, and
      coniferyl alcohol. In addition to GSH, the enzyme could also utilize cysteine as
      a sulfhydryl source. The enzyme activity measured when GSH and trans-cinnamic
      acid were used as substrates was enhanced 2.6- and 5.2-fold by the addition of 50
      [mu]M p-coumaric acid and 7-hydroxycoumarin, respectively. 1H- and 13C-nuclear
      magnetic resonance spectroscopic analysis of the conjugate revealed that the
      enzyme catalyzed the addition of GSH to the olefinic double bond of p-coumaric
      acid. Based on the high activity and the substrate specificity of this enzyme, it
      is possible that this enzyme may be involved in the in vivo conjugation of a
      number of unsaturated phenylpropanoids.

PMID- 12228523
TI  - Chilling-Induced Heat Evolution in Plants.
AB  - Increases in respiration, particularly via the alternative pathway, are observed
      in response to chilling. These increases result in increased heat evolution. We
      have measured increases in heat evolution in response to chilling in a number of
      plant species using a microcalorimeter. After 8 h of exposure to 8[deg]C, heat
      evolution in a variety of chilling-sensitive species increased 47 to 98%. No
      increase in heat evolution was seen with the extremely chilling-sensitive
      ornamental Episcia cupreata Hook. Heat evolution increased only 7 to 22% in the
      chilling-resistant species. Increases in heat evolution were observed when plants
      were chilled in constant light or in the dark, but not when plants were chilled
      at high humidity. Increased capacity to produce respiratory heat after exposure
      to chilling temperatures may contribute to the cold-acclimation process.

PMID- 12228524
TI  - Deuterium Magnetic Resonance Studies of Senescence-Related Changes in the
      Physical Properties of Rose Petal Membrane Lipids.
AB  - The physical properties of membrane lipids in senescing rose (Rosa hybrida L., cv
      Mercedes) petals were studied by deuterium nuclear magnetic resonance (2H-NMR)
      and fluorescence depolarization. All of the 2H-NMR spectra arising from
      deuterated dimyristoylphosphatidylcholine mixed with whole-lipid extracts from
      membranes of petals of different ages had a shape that is characteristic of
      liquid-crystalline lipid at 30[deg]C. Arrhenius plots of the moments of the 2H
      spectra and fluorescence depolarization values measured from 1,6-diphenyl
      hexatriene-labeled rose petal membrane lipid samples indicated that membrane
      lipid order increased with decreasing temperature as well as with increasing age
      of the petals. The latter trend is explained by previously observed increases in
      fatty acid saturation and increases in the sterol-to-phospholipid ratio that
      occur in rose petals during senescence. The 2H-NMR spectra obtained at 0[deg]C
      also contained quadrupolar splitting lines from lipid in the gel phase,
      confirming the occurrence of this phase in membranes from this tissue.

PMID- 12228525
TI  - Stimulation of the Alternative Pathway by Succinate and Malate.
AB  - Stimulation of the cyanide-resistant oxidation of exogenous NADH in potato
      (Solanum tuberosum L. cv Bintje) tuber callus mitochondria was obtained with
      succinate, malate, and pyruvate. Half-maximal stimulation was observed at a
      succinate or malate concentration of 3 to 4 mM, which is considerably higher than
      that found for pyruvate (0.128 mM). No effect of succinate or malate addition was
      found when duroquinone was the electron acceptor. Duroquinol oxidation via the
      alternative pathway was poor and not stimulated by organic acids. Under
      stimulating conditions, no swelling or contraction of the mitochondria could be
      observed. Conversely, variation of the osmolarity did not affect the extent of
      stimulation. However, the assay temperature had a significant effect: no
      stimulation occurred at temperatures below 16 to 20[deg]C. Membrane fluidity
      measurements showed a phase transition at about 17[deg]C. Ubiquinone reduction
      levels were not significantly higher in the presence of succinate and malate, but
      the kinetics of the alternative oxidase were changed in a way comparable to that
      found for stimulation by pyruvate. At low temperatures the alternative oxidase
      displayed "activated" kinetics, and a role for membrane fluidity in the
      stimulation of the alternative pathway by carboxylic acids is suggested.

PMID- 12228526
TI  - A Microscale Technique for Gas Chromatography-Mass Spectrometry Measurements of
      Picogram Amounts of Indole-3-Acetic Acid in Plant Tissues.
AB  - A microscale technique has been developed for routine quantifications of picogram
      amounts of indole-3-acetic acid (IAA) in plant tissues by combined gas
      chromatography-mass spectrometry. Low- and high-resolution selected-ion
      monitoring and selected-reaction-monitoring mass spectrometry techniques were
      compared for selectivity and precision. The best selectivity was obtained with
      selected-reaction-monitoring analysis, and 1-mg samples containing 500 fg of IAA
      could be analyzed accurately with this method. This technique was used to
      investigate the IAA distribution pattern along the longitudinal axis of tobacco
      (Nicotiana tabacum [L.]) leaves. In young, developing leaves an increase of
      endogenous IAA from the leaf tip to the base of the leaf was observed, whereas
      the level of IAA was uniform along this axis in mature leaves.

PMID- 12228527
TI  - Stimulation by Light of Rapid pH Regulation in the Chloroplast Stroma in Vivo as
      Indicated by CO2 Solubilization in Leaves.
AB  - Leaves of Brassica oleracea, Helianthus annuus, and Nicotiana rustica were
      exposed for 20 s to high concentrations of CO2. CO2 uptake by the leaf, which was
      very fast, was measured as a transient increase in the concentration of oxygen.
      Rapid solubilization of CO2 in excess of that which is physically dissolved in
      aqueous phases is proposed to be caused by bicarbonate formation in the stroma of
      chloroplasts, which contain carbonic anhydrase. On this basis, pH values and
      bicarbonate accumulation in the chloroplast stroma were calculated. Buffer
      capacities were far higher than expected on the basis of known concentrations in
      the chloroplast stroma. Moreover, apparent buffer capacities increased with the
      time of exposure to high CO2, and they were higher when the measurements were
      performed in the light than in the dark. During prolonged exposure of leaves to
      16% CO2, calculated bicarbonate concentrations in the chloroplast stroma exceeded
      90 mM in the dark and 120 mM in the light. The observations are interpreted as
      indicating that under acid stress protons are rapidly exported from the
      chloroplasts in exchange for cations, which are imported. The data are discussed
      in terms of effective metabolic pH control by ion transport, first across the
      chloroplast envelope and, then, across the tonoplast of leaf mesophyll cells. The
      direct involvement of the vacuole in the regulation of the chloroplast pH in leaf
      cells is suggested.

PMID- 12228528
TI  - Spinach Leaf Sucrose-Phosphate Synthase and Nitrate Reductase Are
      Phosphorylated/Inactivated by Multiple Protein Kinases in Vitro.
AB  - The regulation of sucrose-phosphate synthase (SPS) and nitrate reductase (NR)
      activities from mature spinach (Spinacia oleracea L.) leaves share many
      similarities in vivo and in vitro. Both enzymes are light/dark modulated by
      processes that involve, at least in part, reversible protein phosphorylation.
      Experiments using desalted crude extracts show that the ATP-dependent
      inactivation of spinach SPS and NR is sensitive to inhibition by glucose-6
      phosphate. Also, a synthetic peptide homolog of the spinach SPS phosphorylation
      site inhibits the ATP-dependent inactivation of both enzymes with a similar
      concentration dependence. We have addressed the possibility that SPS and NR are
      regulated by the same protein kinase by partially purifying the protein kinases
      involved. Three unique kinase activities can be separated by anion-exchange and
      size-exclusion chromatography. Each peak of activity has a different substrate
      specificity. By gel filtration, they have apparent molecular masses of
      approximately 45, 60, and 150 kD. Additionally, the activities of the two smaller
      kinases are dependent on micromolar concentrations of Ca2+, whereas the 150-kD
      kinase is not. Finally, the 150-kD kinase has a subunit molecular mass of about
      65 kD as determined by renaturing the kinase activity in situ following sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis.

PMID- 12228529
TI  - Partial Purification and Characterization of a Calcium-Dependent Protein Kinase
      and an Inhibitor Protein Required for Inactivation of Spinach Leaf Nitrate
      Reductase.
AB  - Evidence is accumulating that the activity of spinach (Spinacia oleracea L.) leaf
      NADH:nitrate reductase (NR) is modulated both in vitro and in vivo by protein
      phosphorylation. From the present study we report the partial purification of the
      two protein factors needed for NR inactivation. We identified NR-protein kinase
      (NR-PK) as a calcium-dependent and metabolite-regulated protein kinase and have
      provided additional evidence that phosphorylation of NR is necessary but not
      sufficient to inactivate the enzyme. The inhibitor protein required for
      inactivation of phospho-NR was purified 625-fold by polyethylene glycol
      fractionation and sequential column chromatography. Using partially purified
      inhibitor protein and NR-PK, we characterized NR inactivation (increased
      sensitivity to Mg2+ inhibition) in a reconstituted in vitro system. NR-PK
      activity was inhibited by a variety of metabolic phosphate esters including di
      hydroxyacetone phosphate, glucose-6-phosphate, and fructose-1,6-bisphosphate.
      Light-to-dark transition experiments with a starchless tobacco (Nicotiana
      sylvestris) mutant, which accumulates phosphate esters during the photoperiod,
      indicated that NR inactivation in vivo might, indeed, be down-regulated by
      metabolites. Additionally, we postulate that cytosolic free calcium could play an
      important role in the regulation of NR activity in vivo.

PMID- 12228530
TI  - Cu2+ Reduction by Tomato Root Plasma Membrane Vesicles.
AB  - Reduction of Cu2+ by plasma membrane vesicles isolated from tomato (Lycopersicon
      esculentum Mill.) roots was investigated. Plants were grown in hydroponic culture
      with complete nutrition for 4 weeks or were deprived of Fe for the last 7 d.
      Plasma membrane vesicles were prepared by aqueous two-phase partitioning.
      Reduction of Cu, Fe, and ferricyanide by plasma membrane vesicles was measured.
      An increase in the activity of all three pyridine-nucleotide-dependent activities
      was noted in plasma membrane preparations from Fe-deficient, compared to Fe
      sufficient, plants. Solubilization and chromatographic separation of two plasma
      membrane electron transport systems indicated that the Fe-chelate reductase was
      probably responsible for reduction of Cu. Assays used a variety of Cu chelates,
      and for each the Cu activity in the assay was determined by the program Geochem
      PC. The rate of reduction of Cu correlated with the level of Cu activity, and
      results support the idea that free Cu2+ and not Cu chelates may serve as the true
      substrate for reduction. Reduction was observed only in assays in which Cu
      activity was equivalent to Cu-enriched or Cu-toxic soils. These results suggest
      that reduction of Cu by tomato root may have little or no physiological relevance
      under conditions experienced by the root in the soil.

PMID- 12228531
TI  - Only the Mature Form of the Plastidic Chorismate Synthase Is Enzymatically
      Active.
AB  - Coding regions of a cDNA for precursor and mature chorismate synthase (CS), a
      plastidic enzyme, from Corydalis sempervirens were expressed in Escherichia coli
      as translational fusions to glutathione-S-transferase. Fusion proteins were
      purified, and precursor and mature forms of CS were then released by proteolytic
      cleavage with factor Xa. Although mature CS was enzymatically active after
      release, activity could be detected neither for the precursor CS nor for
      corresponding glutathione-S-transferase fusion proteins. In contrast, two other
      shikimate pathway enzymes (shikimate kinase and 5-enol-pyruvylshikimate-3
      phosphate synthase) have previously been shown to be as enzymatically active as
      their respective higher molecular weight precursors. By expression of unfused,
      mature CS from C. sempervirens in E. coli, it was possible to obtain large
      quantities of enzymatically active CS protein compared to yields from plant cell
      cultures. Expression levels in E. coli approached 1% of total soluble protein. No
      differences were found between authentic CS isolated from cell cultures and CS
      expressed in and purified from E. coli, which made possible a more detailed
      biochemical characterization of CS. Quaternary structure analysis of the purified
      mature CS indicated that the enzyme exists as a dimer, in contrast to the active
      tetrameric structures determined for E. coli and Neurospora crassa enzymes.

PMID- 12228532
TI  - Regulation of [beta]-Methylcrotonyl-Coenzyme A Carboxylase Activity by
      Biotinylation of the Apoenzyme.
AB  - Regulation of the expression of the gene(s) coding for the 78-kD, biotin
      containing subunit of [beta]-methylcrotonyl-coenzyme A carboxylase (MCCase) was
      investigated in different organs of tomato (Lycopersicon esculantus) plants. The
      specific activity of MCCase is highest in extracts from roots, followed in
      descending order by ripe and ripening fruits, stems, and leaves. The specific
      activity is 10-fold higher in roots than in leaves. However, the steady-state
      levels of the 78-kD subunit of MCCase and its mRNA are approximately equal in
      both roots and leaves. Instead, the difference in MCCase activity between these
      two organs is directly correlated to the biotinylation status of the enzyme's
      biotin-containing subunit. Thus, the lower activity of MCCase in leaves is
      attributed to the reduced biotinylation of the biotin-containing subunit of the
      enzyme. Consistent with this model, a pool of nonbiotinylated enzyme is present
      in leaves, whereas the nonbiotinylated enzyme is undetectable in roots. The
      underbiotinylation of MCCase in leaves is not due to a lack of biotin in this
      organ, since the biotin concentration is 4- to 5-fold higher in leaves than in
      roots. These observations indicate that the posttranslational biotinylation of
      the biotin-containing sub-unit of MCCase is an important mechanism for regulating
      the organ-specific expression of MCCase activity.

PMID- 12228533
TI  - Expressed Sequence Tags from Developing Castor Seeds.
AB  - To expand the availability of genes encoding enzymes and structural proteins
      associated with storage lipid synthesis and deposition, partial nucleotide
      sequences, or expressed sequence tags (ESTs), were obtained for 743 cDNA clones
      derived from developing seeds of castor (Ricinus communis L.). Enrichment for
      seed-specific cDNA clones was obtained by selecting clones that did not
      detectably hybridize to first-strand cDNA from leaf mRNA. Similarly, clones that
      hybridized to storage proteins or other highly abundant mRNA species from
      developing seeds were selected against. To enrich for endomembrane-associated
      proteins, some clones were selected for sequencing by immunological screening
      with antibodies prepared against partially purified endoplasmic reticulum
      membranes. Comparison of the deduced amino acid sequences of the ESTs with the
      public data bases resulted in the assignment of putative identities of 49% of the
      clones selected by differential hybridization and 71% of the clones selected by
      immunological screening. Open reading frames in 100 of the ESTs exhibited higher
      homology to 78 different nonplant gene products than to any previously known
      plant gene product.

PMID- 12228534
TI  - The Role of Potassium Channels in the Temperature Control of Stomatal Aperture.
AB  - We used the patch-clamp technique to examine the effect of temperature (13
      36[deg]C) on the depolarization-activated K channels (KD channels) and on the
      hyperpolarization-activated channels (KH channels) in the plasma membrane of
      Vicia faba guard-cell protoplasts. The steady-state whole-cell conductance of
      both K channel types increased with temperature up to 20[deg]C. However, whereas
      the whole-cell conductance of the KH channels increased further and saturated at
      28[deg]C, that of KD channels decreased at higher temperatures. The unitary
      conductance of both channel types increased with temperature like the rate of
      diffusion in water (temperature quotient of approximately 1.5), constituting the
      major contribution to the conductance increase in the whole cells. The mean
      number of available KH channels was not affected significantly by temperature,
      but the mean number of available KD channels increased significantly between 13
      and 20[deg]C and declined drastically above 20[deg]C. This decrease and the
      reduced steady-state voltage-dependent probability of opening of the KD channels
      above 28[deg]C (because of a shift of voltage dependence by +21 mV) account for
      the depression of the whole-cell KD conductance at the higher temperatures. This
      may be a basic mechanism by which leaves of well-watered plants keep their
      stomata open during heat stress to promote cooling by transpiration.

PMID- 12228535
TI  - Pretreatment of Parsley Suspension Cultures with Salicylic Acid Enhances
      Spontaneous and Elicited Production of H2O2.
AB  - Suspension-cultured cells of parsley (Petroselinum crispum L.) were used to study
      the regulation of extracellular H2O2. After resuspension, the washed cells
      regulated the H2O2 concentration spontaneously to a constant level that was
      greatly increased when the cultures were pretreated for 1 d with salicylic acid
      (SA). The H2O2 level was further increased on addition of a fungal elicitor
      preparation, macromolecular chitosan, the sterol-binding polyene macrolide
      amphotericin B, the G protein-activating peptide mastoparan, or La3+. In all
      cases, this induced H2O2 burst was also greatly enhanced in cell suspensions
      pretreated with SA. Both the spontaneous and the induced H2O2 production were
      decreased by the protein kinase inhibitor K-252a. It is suggested that production
      of extracellular H2O2 occurs by an endogenously controlled plasma membrane enzyme
      complex that requires continuous phosphorylation for function and whose activity
      is increased by pretreatment of the cells with SA. This system can also receive
      various external stimuli, including those resulting from binding of fungal
      elicitor. SA can induce acquired resistance against pathogens. The conditioning
      of the parsley suspension culture by SA represents, therefore, a model for the
      long-term regulation of apoplastic H2O2 concentration by this signal substance,
      as suggested previously for the wound hormone methyl jasmonate.

PMID- 12228536
TI  - Partitioning of Electrons between the Cytochrome and Alternative Pathways in
      Intact Roots.
AB  - To test the hypothesis that the cytochrome pathway is not invariably saturated
      when the alternative pathway is engaged, we titrated root respiration of several
      species with KCN (an inhibitor of the cytochrome pathway), both in the absence
      and presence of an inhibitor of the alternative pathway (salicylhydroxamic acid,
      SHAM). The slopes of the resultant KCN [rho] plots ([rho]cyt) were then used to
      determine whether the cytochrome pathway was saturated in each species. The
      species used were Festuca ovina ssp. ovina L., Phaseolus vulgaris L., and six Poa
      species (Poa pratensis L., Poa compressa L., Poa trivialis L., Poa alpina L., Poa
      costiniana Vick., and Poa fawcettiae Vick.). Although the cytochrome pathway was
      saturated in a number of species (i.e. [rho]cyt values were 1.0), several others
      exhibited [rho]cyt values of less than 0.5. Alternative pathway capacity
      correlated negatively with [rho]cyt, with [rho]cyt values of less than 1.0
      occurring in tissues in which the alternative pathway capacity was greater than
      25 to 30% of total respiration. The species that did not show full engagement of
      the cytochrome pathway rarely exhibited SHAM inhibition in the absence of KCN. We
      conclude that this lack of SHAM inhibition is not due to a lack of alternative
      pathway engagement but rather to the diversion of electrons from the alternative
      pathway to the unsaturated cytochrome path following the addition of SHAM.

PMID- 12228537
TI  - The Wheat Abscisic Acid-Responsive Protein Kinase mRNA, PKABA1, Is Up-Regulated
      by Dehydration, Cold Temperature, and Osmotic Stress.
AB  - The effects of dehydration, cold-temperature treatment, and osmotic and salt
      stress on the expression of an abscisic acid-responsive protein kinase mRNA
      (PKABA1) were determined in wheat (Triticum aestivum L.) seedlings. The PKABA1
      transcript was detectable at basal levels in tissues of nonstressed plants and
      accumulated to higher levels in shoot, scutellar, and root tissues of stressed
      plants. PKABA1 transcript accumulated rapidly within 2 h following dehydration
      and within 24 h following other treatments (cold, osmotic stress, and high salt).
      The accumulation of PKABA1 mRNA could not be separated temporally from that of a
      wheat group 3 late embryogenesis abundant mRNA during dehydration and cold
      treatment. High PKABA1 mRNA levels were observed in field-grown plants growing
      under cold winter conditions but not under warmer summer conditions. A recent
      GenBank data base search indicated that other plant protein kinases with similar
      acidic amino acid stretches as in PKABA1 have been identified, and some of these
      kinases are responsive to environmental signals. These results suggest that
      PKABA1 may be part of general environmental stress responses in wheat.

PMID- 12228538
TI  - Characterization of a C-5,13-Cleaving Enzyme of 13(S)-Hydroperoxide of Linolenic
      Acid by Soybean Seed.
AB  - An activity was found in mature soybean seeds (Glycine max L. cv Century) that
      cleaved 13(S)-hydroperoxy-9(Z),11(E),15(Z)-octadecatrienoic acid (13S-HPOT) into
      13-oxo-9(Z),11(E)-tridecadienoic acid and two isomeric pentenols, 2(Z)-penten-1
      ol and 1-penten-3-ol. Isomeric pentene dimers were also produced and were
      presumably derived from the combination of two pentene radicals. 13(S)
      Hydroperoxy-9(Z),11(E)-octadecadienoic acid (13S-HPOD) was, by contrast, a poor
      substrate. Activity with 13S-HPOT increased 24-fold under anaerobic conditions
      reminiscent of a similar anaerobic promoted reaction of 13S-HPOD catalyzed by
      lipoxygenase (LOX) in the presence of linoleic acid. However, prior to ion
      exchange chromatography, cleavage activity did not require linoleic acid. After
      separation by gel filtration followed by ion-exchange chromatography, cleavage
      activity was lost but reappeared in the presence of either linoleic acid or
      dithiothreitol. Under these conditions cleavage activity was coincident with the
      activity of types 1 and 2 LOX. LOX inhibitors suppressed the cleavage reaction in
      a manner similar to inhibition of LOX activity. Heat-generated alkoxyl radicals
      derived from either 13S-HPOT or 13S-HPOD afforded similar products and yields of
      13-oxo-9(Z),11(E)-tridecadienoic acid compared to the enzymic reaction. The
      product 1-penten-3-ol may be the precursor of the "raw-bean" volatile
      ethylvinylketone.

PMID- 12228539
TI  - Properties of the Peribacteroid Membrane ATPase of Pea Root Nodules and Its
      Effect on the Nitrogenase Activity.
AB  - Peribacteroid membrane vesicles from pea (Pisum sativum) root nodules were
      isolated from membrane-enclosed bacteroids by an osmotic shock. The ATPase
      activity associated with this membrane preparation was characterized, and its
      electrogenic properties were determined. The pH gradient was measured as a change
      of the fluorescence intensity of 9-amino-6-chloro-2-methoxyacridine and the
      membrane potential as a shift of absorbance of bis-(3-propyl-5-oxoisoxazol-4
      yl)pentamethine oxonol. It was demonstrated that the ATPase generates a pH
      gradient as well as a membrane potential across the peribacteroid membrane. The
      reversibility of the ATPase was demonstrated by a light-dependent ATP synthesis
      by peribacteroid membrane vesicles fused with bacteriorhodopsin-phospholipid
      vesicles. The light-driven ATP synthesis by the peribacteroid membrane ATPase was
      completely inhibited by a proton-conducting ionophore. The proton-pumping
      activity of the peribacteroid membrane ATPase could also be demonstrated with
      peribacteroid membrane-enclosed bacteroids, and effects on nitrogenase activity
      were established. At pH values below 7.5, an active peribacteroid membrane ATPase
      inhibited the nitrogenase activity of peribacteroid membrane-enclosed bacteroids.
      At pH values above 8, at which whole cell nitrogenase activity was inhibited, the
      protonpumping activity of the peribacteroid membrane ATPase could partially
      reverse the pH inhibition. Vanadate, an inhibitor of plasma membrane and
      peribacteroid membrane ATPases, stimulated nodular nitrogenase activity. It will
      be proposed that the proton-pumping activity of the peribacteroid membrane ATPase
      in situ is a possible regulator of nodular nitrogenase activity.

PMID- 12228540
TI  - Cold-Specific Induction of a Dehydrin Gene Family Member in Barley.
AB  - An interval on barley (Hordeum vulgare L.) chromosome 7 accounting for
      significant quantitative trait locus effects for winter hardiness were detected
      in a winter (Dicktoo) x spring (Morex) barley population (P.M. Hayes, T. Blake,
      T.H.H. Chen, S. Tragoonrung, F. Chen, A. Pan, and B. Liu [1993] Genome 36: 66
      71). Two members of the barley dehydrin gene family, Dhn1 and Dhn2, were located
      within the region defining the winter hardiness quantitative trait locus effect
      (A. Pan, P.M. Hayes, F. Chen, T. Blake, T.H.H. Chen, T.T.S. Wright, I. Karsai, Z.
      Bedo [1994] Theor Appl Genet 89: 900-910). To investigate the possible role of
      Dhn1 and Dhn2 in winter hardiness, we examined the expression pattern of six
      barley dehydrin gene family members in shoot tissue in response to cold
      temperature. Incubation of 3-week-old barley plants at 2[deg]C resulted in a
      rapid induction of a single 86-kD polypeptide that was recognized by an antiserum
      against a peptide conserved in the dehydrin gene family. Northern blot analysis
      confirmed the induction of an mRNA corresponding to Dhn5. The expression patterns
      of cold-induced dehydrins in shoot tissue for Dicktoo and Morex were identical
      under the conditions studied, in spite of the known phenotypic differences in
      their winter hardiness. These results, together with the allelic structure of
      selected high- and low-survival lines, suggest that the Dicktoo alleles at the
      Dhn1 and Dhn2 may not be the primary determinants of winter hardiness in barley.

PMID- 12228541
TI  - Purification and Characterization of 1-Aminocyclopropane-1-Carboxylic Acid N
      Malonyltransferase from Tomato Fruit.
AB  - 1-Aminocyclopropane-1-carboxylic acid (ACC) can be oxidized to ethylene or
      diverted to the conjugate 1-(malonylamino)cyclopropane-1-carboxylic acid (MACC)
      by an ACC N-malonyltransferase. We developed a facile assay for the ACC N
      malonyltransferase that resolved [14C]MACC from [14C]ACC by thin-layer
      chromatography and detected and quantified them using a radioisotope-imaging
      system. Using this assay, we showed that ACC N-malonyltransferase activity has
      developmental and tissue-specific patterns of expression in tomato (Lycopersicon
      esculentum) fruit. In the pericarp, activity was elevated for several days
      postanthesis, subsequently declined to a basal level, increased 3-fold at the
      onset of ripening, and again declined in overripe fruit. In the seed, activity
      increased throughout embryogenesis, maturation, and desiccation. Treatment of
      fruit with ethylene increased activity 50- to 100-fold in the pericarp. ACC N
      malonyltransferase was purified 22,000-fold to a specific activity of 22,000 nmol
      min-1 mg-1 protein using ammonium sulfate precipitation, DyeMatrex Green A
      affinity, anion-exchange, Cibacron Blue 3GA affinity, hydrophobic interaction,
      and molecular filtration chromatography. Native and sodium dodecyl sulfate
      denatured enzyme showed molecular masses of 38 kD, indicating that the enzyme
      exists as a monomer. The enzyme exhibited a Km for ACC of 500 [mu]M, was not
      inhibited by D- or L-amino acids, and did not conjugate [alpha]-aminoisobutyric
      acid or L-amino acids.

PMID- 12228542
TI  - Evidence for Mass Flow in Flowering Individuals of the Submersed Vascular Plant
      Myriophyllum heterophyllum.
AB  - Myriophyllum heterophyllum Michx. is a rhizomatous submersed aquatic plant that
      produces a short, emergent floral spike. We hypothesized that lacunar pressures
      in emergent spikes should be at or near atmospheric pressure and that a mass flow
      of gases from submersed stems through the rhizome to emergent stems may occur as
      lacunar O2 concentrations and pressures in submersed stems increase during
      photosynthesis. We examined the potential for a pressure gradient ([delta]P) to
      develop along this pathway by measuring diurnal changes in lacunar gas
      composition and pressure in submersed stems of nonflowering plants and emergent
      stems of flowering individuals. Methane release from emergent spikes was also
      monitored during three diurnal cycles to evaluate the hypothesis that the
      [delta]P is maintained by the release of lacunar gases to the atmosphere. Lacunar
      O2 concentrations and pressures in submersed stems increased at sunrise and
      reached maximum levels by midday. Although O2 fluctuated similarly in emergent
      stems, lacunar pressures remained at or near atmospheric pressure, indicating
      that a [delta]P is generated between submersed and emergent stems during
      photosynthesis. Methane release from emergent spikes increased as lacunar
      pressures increased, indicating that rhizome gases are transported through
      emergent stems by mass flow and the [delta]P is maintained by venting lacunar
      gases from emergent spikes. The potential for mass flow in both flowering and
      nonflowering individuals is discussed.

PMID- 12228543
TI  - Purification and Properties of a Unique Nucleotide
      Pyrophosphatase/Phosphodiesterase I That Accumulates in Soybean Leaves in
      Response to Fruit Removal.
AB  - Several unique proteins accumulate in soybean (Glycine max) leaves when the
      developing fruits are removed. In the present study, elevated levels of
      nucleotide pyrophosphatase and phosphodiesterase I activities were present in
      leaves of defruited soybean plants. The soluble enzyme catalyzing these reactions
      was purified nearly 1000-fold, producing a preparation that contained a single 72
      kD polypeptide. The molecular mass of the holoenzyme was approximately 560 kD,
      indicating that the native enzyme was likely octameric. The purified enzyme
      hydrolyzed nucleotide-sugars, nucleotide di- and triphosphates, thymidine
      monophosphate p-nitrophenol, and inorganic pyrophosphate but not nucleotide
      monophosphates, sugar mono- and bisphosphates, or NADH. The subunit and
      holoenzyme molecular masses and the preference for substrates distinguish the
      soybean leaf nucleotide pyrophosphatase/phosphodiesterase I from other plant
      nucleotide pyrophosphatase/phosphodiesterase I enzymes. Also, the N-terminal
      sequence of the soybean leaf enzyme exhibited no similarity to the mammalian
      nucleotide pyrophosphatase/phosphodiesterase I, soybean vegetative storage
      proteins, or other entries in the data bank. Thus, the soybean leaf nucleotide
      pyrophosphatase/phosphodiesterase I appears to be a heretofore undescribed
      protein that is physically and enzymatically distinct from nucleotide
      pyrophosphatase/phosphodiesterase I from other sources, as well as from other
      phosphohydrolytic enzymes that accumulate in soybean leaves in response to fruit
      removal.

PMID- 12228545
TI  - The Electronic Plant Gene Register.

PMID- 12228544
TI  - Elicitor-Induced Spruce Stress Lignin (Structural Similarity to Early
      Developmental Lignins).
AB  - Suspension cultures of Picea abies (L.) Karst released polymeric material into
      the culture medium when treated with an elicitor preparation from the spruce
      needle pathogen Rhizosphaera kalkhoffii. The presence of lignin (about 35%, w/w)
      was demonstrated by phloroglucinol/HCI reactivity and quantitation with
      thioglycolic acid. Carbohydrate (about 14%, w/w) and protein (about 32%, w/w)
      were also detected. Amino acid analysis revealed that hydroxyproline and proline
      predominated. Thioacidolysis and subsequent Raney nickel desulfurization allowed
      the analysis of lignin-building units and interunit bonds. Compared with spruce
      wood lignin, an approximately 20-fold higher relative amount of p-hydroxyphenyl
      units was determined. A high content of p-hydroxyphenyl units is typical for
      certain developmental lignins, such as conifer compression wood and middle
      lamella lignins, as well as all induced cell culture lignins so far analyzed.
      Cross-linkages of the pinoresinol type ([beta]-[beta]) in the excreted cell
      culture lignin were markedly increased, whereas [beta]-1 interunit linkages were
      decreased relative to spruce wood lignin. The amount and nature of cross-linkages
      were shown to be intermediate between those in wood lignin and in enzymatically
      prepared lignins. In summary, the elicitor-induced stress lignin was excreted as
      a lignin-extensin complex that closely resembled early developmental lignins.

PMID- 12228546
TI  - Apomixis: Molecular Strategies for the Generation of Genetically Identical Seeds
      without Fertilization.

PMID- 12228547
TI  - Methanol Emission from Leaves (Enzymatic Detection of Gas-Phase Methanol and
      Relation of Methanol Fluxes to Stomatal Conductance and Leaf Development).
AB  - We recently reported the detection of methanol emissions from leaves (R.
      MacDonald, R. Fall [1993] Atmos Environ 27A: 1709-1713). This could represent a
      substantial flux of methanol to the atmosphere. Leaf methanol production and
      emission have not been investigated in detail, in part because of difficulties in
      sampling and analyzing methanol. In this study we used an enzymatic method to
      convert methanol to a fluorescent product and verified that leaves from several
      species emit methanol. Methanol was emitted almost exclusively from the abaxial
      surfaces of hypostomatous leaves but from both surfaces of amphistomatous leaves,
      suggesting that methanol exits leaves via stomates. The role of stomatal
      conductance was verified in experiments in which stomates were induced to close,
      resulting in reduced methanol. Free methanol was detected in bean leaf extracts,
      ranging from 26.8 [mu]g g-1 fresh weight in young leaves to 10.0 [mu]g g-1 fresh
      weight in older leaves. Methanol emission was related to leaf development,
      generally declining with increasing leaf age after leaf expansion; this is
      consistent with volatilization from a cellular pool that declines in older
      leaves. It is possible that leaf emission could be a major source of methanol
      found in the atmosphere of forests.

PMID- 12228548
TI  - Systemic Responses in Arabidopsis thaliana Infected and Challenged with
      Pseudomonas syringae pv syringae.
AB  - Attack of plants by necrotizing pathogens leads to acquired resistance to the
      same or other pathogens in tissues adjacent to or remotely located from the site
      of initial attack. We have used Arabidopsis thaliana inoculated with the
      incompatible pathogen Pseudomonas syringae pv syringae on the lower leaves to
      test the induction of systemic reactions. When plants were challenged with
      Pseudomonas syringae pv syringae in the upper leaves, bacterial titers remained
      stable in those preinfected on the lower leaves. However, there was a distinct
      decrease in symptoms that correlated with a local and systemic increase in
      salicylic acid (SA) and in chitinase activity. Peroxidase activity only increased
      at the site of infection. No changes in catalase activity were observed, either
      at the local or at the systemic level. No inhibition of catalase could be
      detected in tissue in which the endogenous levels of SA were elevated either
      naturally (after infection) or artificially (after feeding SA to the roots). The
      activity of catalase in homogenates of A. thaliana leaves could not be inhibited
      in vitro by SA. SA accumulation was induced by H2O2 in leaves, suggesting a link
      between H2O2 from the oxidative burst commonly observed during the hypersensitive
      reaction and the induction of a putative signaling molecule leading to system
      acquired resistance.

PMID- 12228549
TI  - Overexpression of [delta]-Pyrroline-5-Carboxylate Synthetase Increases Proline
      Production and Confers Osmotolerance in Transgenic Plants.
AB  - Proline (Pro) accumulation has been correlated with tolerance to drought and
      salinity stresses in plants. Therefore, overproduction of Pro in plants may lead
      to increased tolerance against these abiotic stresses. To test this possibility,
      we overexpressed in tobacco the mothbean [delta]-pyrroline-5-carboxylate
      synthetase, a bifunctional enzyme able to catalyze the conversion of glutamate to
      [delta]-pyrroline-5-carboxylate, which is then reduced to Pro. The transgenic
      plants produced a high level of the enzyme and synthesized 10- to 18-fold more
      Pro than control plants. These results suggest that activity of the first enzyme
      of the pathway is the rate-limiting factor in Pro synthesis. Exogenous supply of
      nitrogen further enhanced Pro production. The osmotic potentials of leaf sap from
      transgenic plants were less decreased under water-stress conditions compared to
      those of control plants. Overproduction of Pro also enhanced root biomass and
      flower development in transgenic plants under drought-stress conditions. These
      data demonstrated that Pro acts as an osmoprotectant and that overproduction of
      Pro results in the increased tolerance to osmotic stress in plants.

PMID- 12228550
TI  - Pollination-Induced Ethylene in Carnation (Role of Pollen Tube Growth and Sexual
      Compatibility).
AB  - The pollen-pistil interactions that result in the stimulation of ethylene
      production and petal senescence in carnation (Dianthus caryophyllus L.) flowers
      were investigated. Pollination of White Sim flowers with Starlight pollen
      elicited an increase in ethylene production by styles, leading to increased petal
      ethylene and premature petal senescence. In contrast, pollination with 87-29G
      pollen led to an early increase in ethylene production, but this was not
      sustained, and did not lead to petal senescence. Both Starlight and 87-29G pollen
      germinated on White Sim stigmas and their tubes grew at similar rates,
      penetrating the length of the style. Crosses between Starlight and White Sim led
      to the production of viable seeds, whereas 87-29G pollen was infertile on White
      Sim flowers. Pollination of other carnations with 87-29G elicited ethylene
      production and petal senescence and led to the production of viable seeds. These
      results suggest that physical growth of pollen tubes is insufficient to elicit a
      sustained increase in ethylene production or to lead to the production of signals
      necessary for elicitation of petal ethylene production and senescence. Rather,
      the cell-cell recognition reactions leading to sexual compatibility in Dianthus
      appear to play a role in this interorgan signaling after pollination.

PMID- 12228551
TI  - Impaired Wound Induction of 3-Deoxy-D-arabino-heptulosonate-7-phosphate (DAHP)
      Synthase and Altered Stem Development in Transgenic Potato Plants Expressing a
      DAHP Synthase Antisense Construct.
AB  - Potato (Solanum tuberosum L.) cells were transformed with an antisense DNA
      construct encoding part of 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP)
      synthase (EC 4.1.2.15), the first enzyme of the shikimate pathway, to examine the
      role(s) of this protein in plant growth and development. Chimeric DNA constructs
      contained the transcript start site, the first exon, and part of the first intron
      of the shkA gene in antisense or sense orientations under the control of the
      cauliflower mosaic virus 35S promoter. Some, but not all, of the transgenic
      plants expressing antisense DAHP synthase RNA showed reduced levels of wound
      induced DAHP synthase enzyme activity, polypeptide, and mRNA 12 and 24 h after
      wounding. No alteration in the wound induction of DAHP synthase gene expression
      was observed in transgenic potato tubers containing the chimeric sense construct.
      Reduced steady-state levels of DAHP synthase mRNA were observed in stem and shoot
      tip tissue. Some plants with the chimeric antisense construct had reduced stem
      length, stem diameter, and reduced stem lignification.

PMID- 12228552
TI  - The Effects of Cytokinin and Light on Hypocotyl Elongation in Arabidopsis
      Seedlings Are Independent and Additive.
AB  - Cytokinin has been reported to mimic some of the effects of light on de
      etiolation responses in dark-grown Arabidopsis seedlings. The interaction between
      cytokinin and light was examined by analyzing cytokinin dose and light fluence
      effects on hypocotyl elongation in wild-type and mutant Arabidopsis seedlings
      with defects in light or hormone responses. It was found that (a) cytokinin and
      light-response systems have independent and additive effects on the inhibition of
      hypocotyl elongation and (b) either cytokinin or light can saturate the
      morphogenic responses. As a consequence, cytokinin has no effect on hypocotyl
      elongation under normal growth conditions because light levels saturate the
      hypocotyl inhibition response. To determine whether a functional light-response
      pathway is required for cytokinin responses, light-insensitive long hypocotyl
      (hy) mutants were tested for cytokinin responses. The hy mutants (hy1 to hy6) had
      normal cytokinin responses, except phyB-1 (hy3-1), in which hypocotyl elongation
      was insensitive to cytokinin. Cytokinin insensitivity in phyB-1 was attributed to
      an indirect effect of the mutation on cytokinin responses. The effects of
      cytokinin on the inhibition of hypocotyl elongation are largely mediated by
      ethylene, and blocking the ethylene-response pathway through the action of a
      cytokinin-resistant, ethylene-insensitive mutant (ckr1/ein2) had no effect on the
      light inhibition of hypocotyl elongation. These results do not support the idea
      that cytokinin mediates the action of light on hypocotyl elongation.

PMID- 12228553
TI  - Photosynthetic Shutdown in Chlorella NC64A Associated with the Infection Cycle of
      Paramecium bursaria Chlorella Virus-1.
AB  - The effects of the algal virus Paramecium bursaria Chlorella virus-1 on the
      photosynthetic physiology of its host, Chlorella NC64A, was studied by observing
      changes in Chl fluorescence quenching and O2 exchange. Metabolic changes were
      calibrated against electron microscopic analysis of the morphological changes
      that occur during the infection cycle. It takes approximately 10 h from
      attachment of the virus to final lysis of the host cell, so a complete infection
      cycle can be observed continuously in one experiment. During the early stages of
      the infection cycle many rapid changes occurred in the host cell's metabolism and
      these were reflected in changes of photosynthetic and respiratory rates. The
      dramatic inhibition of photosynthesis in Chlorella NC64A cells by P. bursaria
      Chlorella virus-1 has facilitated the use of fluorescence quenching as an
      accurate measure of the first phase of viral infection (attachment and
      penetration of the host cell) and the extent to which a population of host cells
      is infected. Effects of temperature and cation requirement of the infection cycle
      are described. The relevance of our observations to the events observed during
      viral infection of higher plants is discussed.

PMID- 12228554
TI  - Suppression of an Isoflavonoid Phytoalexin Defense Response in Mycorrhizal
      Alfalfa Roots.
AB  - Isoflavonoids and steady-state mRNA levels of phenylalanine ammonia-lyase,
      chalcone isomerase, and isoflavone reductase were followed during a rapid, nearly
      synchronous infection of alfalfa (Medicago sativa L.) roots by the vesicular
      arbuscular fungus Glomus intraradices (Schenck & Smith) to test whether
      previously indicated suppression of the host defense response is regulated by
      changes in the steady-state mRNA level. Relative amounts of steady-state
      phenylalanine ammonia-lyase mRNA in the mycorrhizal roots doubled between d 14
      and 18 and then immediately declined by 75% to reach and maintain a value lower
      than the control roots through d 21. Relative levels of chalcone isomerase mRNA
      in the inoculated roots increased 6-fold between d 14 and 17 and then decreased
      rapidly to the control level. Isoflavone reductase mRNA was not induced by
      mycorrhizal colonization. High-performance liquid chromatography, proton-nuclear
      magnetic resonance, and fast atom bombardment-mass spectrometry analyses showed
      consistent increases in formononetin levels and transient increases in medicarpin
      3-O-glycoside and formononetin conjugates in the inoculated roots when
      colonization began. As colonization increased, levels of formononetin conjugates
      declined in mycorrhizal roots below those in uncolonized controls. Medicarpin
      aglycone, an alfalfa phytoalexin normally associated with pathogenic infections,
      was not detected at any stage. These findings supply detailed evidence that,
      during early colonization of plant roots by symbiotic Glomus, defense transcripts
      are induced and then subsequently suppressed.

PMID- 12228555
TI  - A Short-Term Decrease in Nitrogenase Activity (C2H2 Reduction) Is Induced by
      Exposure of Soybean Shoots to Their CO2 Compensation Point.
AB  - Photosynthesis and nitrogenase acetylene-reducing activity (ARA) were measured in
      soybeans (Glycine max [L.] Merr.) in which the shoots were exposed for 48 h to 60
      [mu]L L-1 CO2, a value corresponding to their CO2 compensation point. Six hours
      after the beginning of the light period at low CO2, the ARA started to decrease,
      reaching a rate of 50% of the control rate in 14 to 24 h and 20% of the control
      rate in 34 to 38 h after the beginning of the CO2 treatment. At these times,
      there was no net photosynthesis, and the transpiration rate was 20% lower than
      that in the control plants. An increase in the partial pressure of O2 around the
      nodules alleviated this inhibition of ARA. The maximal ARA achieved at 40 kPaO2
      was 3 times higher than that at 20 kPa O2 and similar to the maximal ARA of the
      control plants. It was argued that the decrease in ARA of soybean exposed to the
      CO2 compensation point was due to a decrease in the nodule's permeability to O2
      diffusion.

PMID- 12228556
TI  - Diurnal Regulation of Leaf Blade Elongation in Rice by CO2 (Is it Related to
      Sucrose-Phosphate Synthase Activity?).
AB  - The relationship between leaf blade elongation rates (LER) and sucrose-phosphate
      synthase (SPS) activity was investigated at different times during ontogeny of
      rice (Oryza sativa L. cv Jarrah) grown in flooded soil at either 350 or 700 [mu]L
      CO2 L-1. High CO2 concentrations increased LER of expanding blades and in vivo
      activity (Vlimiting) SPS activity of expanded blades during the early vegetative
      stage (21 d after planting [DAP]), when tiller number was small and growing
      blades were strong carbohydrate sinks. Despite a constant light environment,
      there was a distinct diurnal pattern in LER, Vlimiting SPS activity, and
      concentration of soluble sugars, with an increase in the early part of the light
      period and a decrease later in the light period. The strong correlation (r =
      0.65) between LER and Vlimiting SPS activity over the diurnal cycle indicated
      that SPS activity played an important role in controlling blade growth. The
      higher Vlimiting SPS activity at elevated CO2 at 21 DAP was caused by an increase
      in the activation state of the enzyme rather than an increase in Vmax. Fructose
      and glucose accumulated to a greater extent than sucrose at high CO2 and may have
      been utilized for synthesis of cell-wall components, contributing to higher
      specific leaf weight. By the mid-tillering stage (42 DAP), CO2 enrichment
      enhanced Vlimiting and Vmax activities of source blades. Nevertheless, LER was
      depressed by high CO2, probably because tillers were stronger carbohydrate sinks
      than growing blades.

PMID- 12228557
TI  - Violaxanthin Cycle Pigment Contents in Potato and Tobacco Plants with Genetically
      Reduced Photosynthetic Capacity.
AB  - The influence of photosynthetic activity on the light-dependent adaptation of the
      pool size of the violaxanthin cycle pigments (violaxanthin + antheraxanthin +
      zeaxanthin) was studied in leaves of wild-type and transgenic potato (Solanum
      tuberosum L.) and tobacco (Nicotiana tabacum L.) plants. The genetically
      manipulated plants expressed an antisense mRNA coding for the chloroplastic
      fructose-bisphosphatase. Chl fluorescence quenching analysis revealed that the
      transformed plants exhibited a greatly impaired electron transport capacity.
      Light-limited and light-saturated non-photochemical quenching was strongly
      enhanced in the mRNA antisense potato plants. After 7 d of adaptation at various
      high photosynthetic photon flux densities (PPFDs), the violaxanthin cycle pool
      size increased, with a progressive elevation in PPFD. The pool size was higher
      for transgenic potatoes than for wild-type plants at all PPFDs. This difference
      vanished when pool size was correlated with the PPFD in excess of photosynthesis,
      as indicated by the epoxidation state of the violaxanthin cycle. Contrasting
      results were obtained for tobacco; in this species, photosynthetic activity did
      not affect the pool size. We conclude that regulatory mechanisms exist in potato,
      by which photosynthetic activity can influence the violaxanthin cycle pool size.
      Furthermore, evidence is provided that this adaptation of the pool size may
      contribute to an improved photoprotection of the photosynthetic apparatus under
      high-light conditions. However, tobacco plants seem to regulate their pool size
      independently of photosynthetic activity.

PMID- 12228558
TI  - Rhizobial Nodulation Factors Stimulate Mycorrhizal Colonization of Nodulating and
      Nonnodulating Soybeans.
AB  - Legumes form tripartite symbiotic associations with noduleinducing rhizobia and
      vesicular-arbuscular mycorrhizal fungi. Co-inoculation of soybean (Glycine max
      [L.] Merr.) roots with Bradyrhizobium japonicum 61-A-101 considerably enhanced
      colonization by the mycorrhizal fungus Glomus mosseae. A similar stimulatory
      effect on mycorrhizal colonization was also observed in nonnodulating soybean
      mutants when inoculated with Bradyrhizobium japonicum and in wild-type soybean
      plants when inoculated with ineffective rhizobial strains, indicating that a
      functional rhizobial symbiosis is not necessary for enhanced mycorrhiza
      formation. Inoculation with the mutant Rhizobium sp. NGR[delta]nodABC, unable to
      produce nodulation (Nod) factors, did not show any effect on mycorrhiza. Highly
      purified Nod factors also increased the degree of mycorrhizal colonization. Nod
      factors from Rhizobium sp. NGR234 differed in their potential to promote fungal
      colonization. The acetylated factor NodNGR-V (MeFuc, Ac), added at concentrations
      as low as 10-9 M, was active, whereas the sulfated factor, NodNGR-V (MeFuc, S),
      was inactive. Several soybean flavonoids known to accumulate in response to the
      acetylated Nod factor showed a similar promoting effect on mycorrhiza. These
      results suggest that plant flavonoids mediate the Nod factor-induced stimulation
      of mycorrhizal colonization in soybean roots.

PMID- 12228559
TI  - Potassium Fluxes in Chlamydomonas reinhardtii (I.Kinetics and Electrical
      Potentials).
AB  - Potassium influx and cellular [K+] were measured in the unicellular green alga
      Chlamydomonas reinhardtii after pretreatment in either 10 or 0 mM external K+
      ([K]0). K+ (42K+ or 86Rb+) influx was mediated by a saturable, high-affinity
      transport system (HATS) at low [K+]0 and a linear, low-affinity transport system
      at high [K+]o. The HATS was typically more sensitive to metabolic inhibition (and
      darkness) than the low-affinity transport system. Membrane electrical potentials
      were determined by measuring the equilibrium distribution of
      tetraphenylphosphonium. These values, together with estimates of cytoplasmic [K+]
      (B. Malhotra and A.D.M. Glass [1995] Plant Physiol 108: 1537-1545), demonstrated
      that at 0.1 mM [K+]0 K+ uptake must be active. At higher [K+]0 (>0.3 mM) K+
      influx appeared to be passive and possibly channel mediated. When cells were
      deprived of K+ for 24 h, the Vmax for the HATS increased from 50 x 10-6 to 85 x
      10-6 nmol h-1 cell-1 and the Km value decreased from 0.25 to 0.162 mM. Meanwhile,
      cellular [K+] declined from 24 x 10-6 to 9 x 10-6 nmol cell-1. During this period
      influx increased exponentially, reaching its peak value after 18 h of K+
      deprivation. This increase of K+ influx was not expressed when cells were exposed
      to inhibitors of protein synthesis. The use of 42K+ and 86Rb+ in parallel
      experiments demonstrated that Chlamydomonas discriminated in favor of K+ over
      Rb+, and this effect increased with the duration of K+ deprivation.

PMID- 12228560
TI  - Potassium Fluxes in Chlamydomonas reinhardtii (II. Compartmental Analysis).
AB  - 42K+ and 86Rb+ were used to determine the subcellular distribution of potassium
      in Chlamydomonas reinhardtii by compartmental analysis. In both wild type and a
      mutant strain, three distinct compartments (referred to as I, II, and III) were
      apparent. Using 42K+, we found that these had half-lives for K+ exchange of 1.07
      min, 12.8 min, and 2.9 h, respectively, in wild-type cells and 0.93 min, 14.7
      min, and 9.8 h, respectively, for the mutants. Half-lives were not significantly
      different when 86Rb+ was used to trace K+. Compartments I and II probably
      correspond to the cell wall and cytoplasm, respectively. Based on the lack of a
      large central vacuole in Chlamydomonas, the effect of a dark pretreatment on the
      kinetic properties of compartment III and the similarity between the [K+] of
      compartment III and that of isolated chloroplasts, this slowly exchanging
      compartment was identified as the chloroplast. Growth of wild-type cells at 100
      [mu]M (instead of 10 mM K+) caused no change of cytoplasmic [K+] but reduced
      chloroplast [K+] very substantially. The mutants failed to grow at 100 [mu]M K+.

PMID- 12228561
TI  - The Rhizobial hemA Gene Is Required for Symbiosis in Species with Deficient
      [delta]-Aminolevulinic Acid Uptake Activity.
AB  - Most rhizobial hemA mutants induce root nodules on their respective legume hosts
      that lack nitrogen fixation activity and leghemoglobin expression. However, a
      Bradyrhizobium japonicum hemA mutant elicits effective nodules on soybean, and we
      proposed previously that synthesis and uptake of the heme precursor [delta]
      aminolevulinic acid (ALA) by the plant and bacterial symbiont, respectively,
      allow mutant rescue (I. Sangwan, M.R. O'Brian [1991] Science 251: 1220-1222). In
      the present work, the B. japonicum hemA mutant MLG1 elicited normal nodules on
      three hosts, including cowpea, a plant that is not effectively nodulated by a
      hemA mutant of Rhizobium sp. These data indicate that B. japonicum rather than
      soybean possesses the unique trait that allows normal nodule development by a
      hemA mutant. Cowpea expressed glutamate-dependent ALA formation activity in
      nodules induced by B. japonicum strains I110 or MLG1 and by Rhizobium sp. ANU240.
      Exogenous ALA was taken up by B. japonicum bacteroids isolated from soybean or
      cowpea nodules, and the kinetics of uptake were biphasic. By comparison,
      Rhizobium sp. ANU240 had very low ALA uptake activity. In addition, ALA uptake
      was observed in cultured cells of B. japonicum but not in cultured cells of three
      other rhizobial species tested. We suggest that the differential success of
      legume-rhizobial hemA symbioses is due to an ALA uptake activity in B. japonicum
      that is deficient in other rhizobia, thereby further validating the ALA rescue
      hypothesis.

PMID- 12228562
TI  - Selection for Hyoscyamine and Cinnamoyl Putrescine Overproduction in Cell and
      Root Cultures of Hyoscyamus muticus.
AB  - Hairy root cultures of Hyoscyamus muticus have been shown to produce stable
      levels of tropane alkaloids comparable to those found in whole plants. In
      contrast, cell cultures of this and other solanaceous species produce only trace
      amounts of alkaloids but can be used for selection of metabolic variants. We have
      taken advantage of both systems and the ability to convert between them in vitro
      in an effort to select for increased production of the tropane alkaloid
      hyoscyamine. Hairy roots were converted into cell suspensions by addition of 1
      mg/L 2,4-dichlorophenoxyacetic acid to Murashige-Skoog medium (T. Murashige and
      F. Skoog [1962] Physiol Plant 15: 473-497) and screened for resistance to the
      amino acid analog p-fluorophenylalanine (PFP). Cells that could grow in media
      containing 400 [mu]M PFP were selected and cloned from single cells. The
      resistant cells accumulated high levels of cinnamoyl putrescines, which share the
      same biosynthetic precursors as hyoscyamine. Hairy root cultures were regenerated
      from both PFP-sensitive and PFP-resistant cells by removing 2,4
      dichlorophenoxyacetic acid from the medium. Resistance to PFP continued to be
      expressed in regenerated roots. Higher levels of hyoscyamine were found in hairy
      roots regenerated from PFP-resistant cells than were found in controls. We
      suggest that the precursors overproduced by the PFP-resistant cells can be
      diverted into the hyoscyamine pathway upon the regeneration of root cultures.

PMID- 12228563
TI  - In Vivo Regulatory Phosphorylation of Soybean Nodule Phosphoenolpyruvate
      Carboxylase.
AB  - In this report we provide evidence that cytosolic phosphoenolpyruvate carboxylase
      (PEPC) in soybean (Glycine max L.) root nodules is regulated in vivo by a seryl
      phosphorylation cycle, as with the C4, Crassulacean acid metabolism, and C3 leaf
      isoforms. Pretreatment of parent plants by stem girdling for 5 or 14 h caused a
      significant decrease in the apparent phosphorylation state of nodule PEPC, as
      indicated by the 50% inhibition constant (L-malate) and specific activity values
      assayed at suboptimal conditions, whereas short-term darkness alone was without
      effect. However, extended (26 h) darkness led to the formation of a relatively
      dephosphorylated nodule PEPC, an effect that was reversed by illuminating the
      darkened plants for 3 h. This reversal of the apparent phosphorylation state in
      the light was prevented by concomitant stem girdling. In contrast, the optimal
      activity of nodule PEPC and its protein level showed little or no change in all
      pretreated plants. These results suggest that the phosphorylation state of PEPC
      in soybean root nodules is possibly modulated by photosynthate transported
      recently from the shoots. In situ [32P]orthophosphate labeling,
      immunoprecipitation, and phosphoamino acid analyses confirmed directly that PEPC
      in detached intact soybean nodules is phosphorylated on a serine residue(s).

PMID- 12228564
TI  - Influence of Elevated Fructose-2,6-Bisphosphate Levels on Starch Mobilization in
      Transgenic Tobacco Leaves in the Dark.
AB  - The aim of this work was to study the effect of elevated fructose-2,6
      bisphosphate (Fru-2,6-bisP) levels on carbohydrate metabolism in leaves in the
      dark. In transgenic tobacco (Nicotiana tabacum L.) lines containing mammalian 6
      phosphofructo-2-kinase activity there is an inverse relationship between the
      level of Fru-2,6-bisP in leaves and the rate of starch breakdown in the dark.
      Estimates of the flux response coefficient for the rate of net starch degradation
      with respect to changes in Fru-2,6-bisP level are -0.57 for whole leaves and 
      0.69 to -0.89 for excised leaf discs. We suggest that this decrease in the net
      rate of starch breakdown is caused, at least in part, by stimulation of
      unidirectional starch synthesis. Measurements of the levels of metabolic
      intermediates and the metabolism of [U-14C]glucose indicate that the stimulation
      of starch synthesis in the dark is a result of high Fru-2,6-bisP levels,
      increasing the 3-phosphoglycerate:inorganic phosphate ratio in leaves. We argue
      that the observed response to changes in the level of Fru-2,6-bisP are effected
      through activation of pyrophosphate:fructose-6-phosphate 1-phosphotransferase.
      However, the extent to which changes in Fru-2,6-bisP influence starch metabolism
      in wild-type plants is not known.

PMID- 12228565
TI  - Localization and Characterization of Peroxidases in the Mitochondria of Chilling
      Acclimated Maize Seedlings.
AB  - We present evidence of two peroxidases in maize (Zea mays L.) mitochondria. One
      of these uses guaiacol and the other uses cytochrome c as the electron donor.
      Treatments of fresh mitochondria with protease(s) indicate that ascorbate and
      glutathione peroxidases are likely bound to the mitochondria as cytosolic
      contaminants, whereas guaiacol and cytochrome peroxidases are localized within
      the mitochondria. These two mitochondrial peroxidases are distinct from
      contaminant peroxidases and mitochondrial electron transport enzymes. Cytochrome
      peroxidase is present within the mitochondrial membranes, whereas guaiacol
      peroxidase is loosely bound to the mitochondrial envelope. Unlike other cellular
      guaiacol peroxidases, mitochondrial guaiacol peroxidase is not glycosylated.
      Digestion of lysed mitochondria with trypsin activated mitochondrial guaiacol
      peroxidase but inhibited cytochrome peroxidase. Isoelectric focusing gel analysis
      indicated guaiacol peroxidase as a major isozyme (isoelectric point 6.8) that is
      also activated by trypsin. No change in the mobility of guaiacol peroxidase due
      to trypsin treatment on native polyacrylamide gel electrophoresis was observed.
      Although both peroxidases are induced by chilling acclimation treatments
      (14[deg]C), only cytochrome peroxidase is also induced by chilling (4[deg]C).
      Because chilling induces oxidative stress in the maize seedlings and the
      mitochondria are a target for oxidative stress injury, we suggest that
      mitochondrial peroxidases play a role similar to catalase in protecting
      mitochondria from oxidative damage.

PMID- 12228566
TI  - Lipo-chitooligosaccharide Nodulation Signals from Rhizobium meliloti Induce Their
      Rapid Degradation by the Host Plant Alfalfa.
AB  - Extracellular enzymes from alfalfa (Medicago sativa L.) involved in the
      degradation of nodulation (Nod) factors could be distinguished by their different
      cleavage specificities and were separated by lectin affinity chromatography. A
      particular glycoprotein was able to release an acylated lipo-disaccharide from
      all tested Nod factors having an oligosaccharide chain length of four or five
      residues. Structural modifications of the basic lipo-chitooligosaccharide did not
      affect the cleavage site and had only weak influence on the cleavage efficiency
      of Nod factors tested. The acylated lipo-trisaccharide was resistant to
      degradation. When alfalfa roots were preincubated with Nod factors at nanomolar
      concentrations, the activity of the dimer-forming enzyme was stimulated up to 6
      fold within a few hours. The inducing activity of Nod factors decreased in the
      order NodRm-IV(C16:2,Ac,S) > NodRm-IV(C16:2,S) and NodRm-V(C16:2,Ac,S) > NodRm
      V(C16:2,S) > NodRm-IV(C16:0,S) > NodRm-IV(C16:2). Pretreatment with NodRm
      III(C16:2) as well as unmodified chitooligosaccharides did not stimulate the
      dimer-forming enzyme. Roots preincubated with Rhizobium meliloti showed similar
      stimulation of the dimer-forming activity. Mutant strains unable to produce Nod
      factors did not enhance the hydrolytic activity. These results indicate a rapid
      feedback inactivation of Nod signals after their perception by the host plant
      alfalfa.

PMID- 12228567
TI  - Partial Purification of a Na+ -ATPase from the Plasma Membrane of the Marine Alga
      Heterosigma akashiwo.
AB  - A Na+ -ATPase was partially purified from plasma membranes of the marine alga
      Heterosigma akashiwo. The plasma membranes of H. akashiwo cells were collected by
      differential centrifugation with subsequent discontinuous gradient
      centrifugation. Na+ -ATPase activity was associated with the resultant plasma
      membrane fraction and was stimulated to the greatest extent in the presence of
      100 to 200 mM Na+, 10 mM K+, and 5 mM Mg2+ ions, pH 8.0. The Km value for Na+
      ions was 12.2 mM. An apparent Km value for ATP was 880 [mu]M. A 140-kD
      phosphorylated intermediate was also detected in the same fraction in the
      presence of both Mg2+ and Na+ ions, and this protein was dephosphorylated upon
      the addition of K+ ions. We could partially purify the 140-kD protein after
      solubilization by Suc monolaurate and fractionation by sequential column
      chromatography on Sephacryl S-300, DEAE-Sepharose CL-6B, and Mono-Q columns. The
      purified 140-kD polypeptide could also be phosphorylated and be detected after
      acid sodium dodecyl sulfate-polyacryl-amide gel electrophoresis in the presence
      of Na+ and Mg2+ ions.

PMID- 12228568
TI  - Opposite Regulation of the Copy Number and the Expression of Plastid and
      Mitochondrial Genes by Light and Acetate in the Green Flagellate Chlorogonium.
AB  - In the unicellular green alga Chlorogonium elongatum (Chlamydomonadaceae), the
      formation of both the photosynthetic and the respiratory apparatus is under the
      control of light and acetate. Autotrophically cultured cells possess a 3-fold
      higher copy number of the plastid genes rbcL and psbA than cells cultivated in
      the dark with acetate (heterotrophic cells). Under mixotrophic conditions (light
      and acetate), both genes are present at an intermediate level. This pattern is
      repeated at the mRNA level. The amounts of rbcL and psbA mRNAs are approximately
      3-fold higher in autotrophic cells than in heterotrophic ones and are
      intermediate in mixotrophic cells. As expected, the copy number of the nuclear
      encoded rbcS gene is constant irrespective of the applied culture conditions.
      RbcS mRNA, however, is 7-fold more frequent in autotrophic than in heterotrophic
      cells. Again, mixotrophic cells show an intermediate level. In contrast to genes
      encoding plastid proteins, the copy number and transcript level of the
      mitochondrial cob gene are approximately 5-fold higher in heterotrophic cells
      than in autotrophic ones. As before, mixotrophic cells take an intermediate
      position. Therefore, light and acetate control the genes involved in the
      formation of either the photosynthetic or the respiratory apparatus in a
      coordinated but opposite manner.

PMID- 12228569
TI  - End-Product Control of Carbon Metabolism in Culture-Grown Sugar Beet Plants
      (Molecular and Physiological Evidence on Accelerated Leaf Development and
      Enhanced Gene Expression).
AB  - Sugar beet (Beta vulgaris L.) seedlings were grown on media containing 90 to 300
      mM sucrose or glucose. Compared to controls, sugar-grown plants had higher growth
      rate, photosynthesis, and leaf sugar levels. The steady-state level of
      transcripts increased significantly for the small subunit of ribulose-1,5
      bisphosphate carboxylase/oxygenase (Rubisco) (rbcS) and the cytosolic fructose
      1,6-bisphosphatase and moderately for the Rubisco large subunit (rbcL). The
      transcript level of sucrose phosphate synthase remained unchanged. Fructose-1,6
      bisphosphatase and Rubisco activities did not change in the presence of sugars,
      but that of sucrose phosphate synthase increased (44 and 90% under selective and
      nonselective assay conditions, respectively). Accelerated leaf development was
      indicated by (a) autoradiograms of leaves that showed that sucrose loading
      occurred earlier, (b) export capacity that also occurred earlier but, after about
      2 weeks, differences were not detectable, and (c) sucrose synthase activity that
      declined significantly. Several conclusions emerged: (a) response was nonosmotic
      and gene and sugar specific, (b) sugars caused accelerated leaf development and
      sink-to-source transition, (c) enhanced gene expression was due to advanced leaf
      development, and (d) whereas Rubisco and cytosolic fructose-1,6-bisphosphatase
      genes were sugar repressed in mature leaves of greenhouse-grown plants, they were
      unaffected in mature, culture-grown leaves. To our knowledge, these data provide
      the first evidence in higher plants that, depending on the
      physiological/developmental context of leaves, sugars lead to differential
      regulation of the same gene.

PMID- 12228570
TI  - Isolation and Characterization of a Protein Associated with Carotene Globules in
      the Alga Dunaliella bardawil.
AB  - The halotolerant alga Dunaliella bardawil accumulates very large amounts of
      [beta]-carotene when exposed to high light intensity. The accumulated [beta]
      carotene is concentrated in small, oily globules within the chloroplast and has
      been suggested to protect the alga against photodamage by high irradiation (A.
      Ben-Amotz, A. Katz, M. Avron [1982] J Phycol 18:529-537;A. Ben-Amotz, M. Avron
      [1983] Plant Physiol 72: 593-597; A. Ben-Amotz, A. Shaish, M. Avron [1989] Plant
      Physiol 91: 1040-1043). A 38-kD protein was identified and purified from [beta]
      carotene globules and was designated carotene globule protein (Cgp). Induction of
      Cgp occurs in parallel with [beta]-carotene accumulation in D. bardawil grown
      under different inductive conditions. Cgp is overproduced in a constitutive
      mutant strain that overproduces [beta]-carotene and is not detected in Dunaliella
      salina, a species that does not accumulate [beta]-carotene. Cgp production was
      not suppressed by norflurazon, an inhibitor of [beta]-carotene synthesis that
      leads to accumulation of the carotenoid precursor phytoene. Immunogold-labeling
      analysis by electron microscopy demonstrates that the protein is localized at the
      periphery of the globules. Proteolytic cleavage by trypsin enhances the
      coalescence and destruction of the globules, in parallel with Cgp disappearance.
      It is suggested that the function of Cgp is to stabilize the structure of the
      globules within the chloroplast.

PMID- 12228571
TI  - Carbon Partitioning in Eelgrass (Regulation by Photosynthesis and the Response to
      Daily Light-Dark Cycles).
AB  - Diel variations in rates of C export, sucrose-phosphate synthase (SPS) and
      sucrose synthase (SS) activity, and C reserves were investigated in Zostera
      marina L. (eelgrass) to elucidate the environmental regulation of sucrose
      formation and partitioning in this ecologically important species. Rates of C
      flux and SPS activity increased with leaf age, consistent with the ontogenic
      transition from sink to source status. Rates of C export and photosynthesis were
      low but quantitatively consistent with those of many terrestrial plant species.
      The Vmax activity of SPS approached that of maize, but substrate-limited rates
      were 20 to 25% of Vmax, indicating a large pool of inactive SPS. SPS was
      unresponsive to the day/night transition or to a 3-fold increase in
      photosynthesis generated by high [CO2] and showed little sensitivity to inorganic
      phosphate. Consequently, regulation of eelgrass SPS appeared similar to starch-
      rather than to sugar-accumulating species even though eelgrass accumulates
      sucrose. Leaf [sucrose] was constant and high throughout the diel cycle, which
      may contribute to the down-regulation of SPS. Root sucrose synthase activity was
      high but showed no response to nocturnal anoxia. Root [sucrose] also showed no
      diel cycle. The temporal stability of [sucrose] confers an ability for eelgrass
      to buffer the effects of prolonged light limitation that may be key to its
      survival and ecological success in environments subject to periods of extreme
      light limitation and chaotic daily variation in light availability.

PMID- 12228572
TI  - Hydrogen Peroxide Stimulates Salicylic Acid Biosynthesis in Tobacco.
AB  - Hydrogen peroxide induced the accumulation of free benzoic acid (BA) and
      salicylic acid (SA) in tobacco (Nicotiana tabacum L. cv Xanthi-nc) leaves. Six
      hours after infiltration with 300 mM H2O2, the levels of BA and SA in leaves
      increased 5-fold over the levels detected in control leaves. The accumulation of
      BA and SA was preceded by the rapid activation of benzoic acid 2-hydroxylase
      (BA2H) in the H2O2-infiltrated tissues. This enzyme catalyzes the formation of SA
      from BA. Enzyme activation could be reproduced in vitro by addition of H2O2 or
      cumene hydroperoxide to the assay mixture. H2O2 was most effective in vitro when
      applied at 6 mM. In vitro activation of BA2H by peroxides was inhibited by the
      catalase inhibitor 3-amino-1,2,4-triazole. We suggest that H2O2 activates SA
      biosynthesis via two mechanisms. First, H2O2 stimulates BA2H activity directly or
      via the formation of its substrate, molecular oxygen, in a catalase-mediated
      reaction. Second, higher BA levels induce the accumulation of BA2H protein in the
      cells and provide more substrate for this enzyme.

PMID- 12228573
TI  - The Use of Nonaqueous Fractionation to Assess the Ionic Composition of the
      Apoplast during Fruit Ripening.
AB  - We have examined the possibility that pectin solubilization and cell separation
      in fruit may be due to organic acids disrupting calcium bridges between pectic
      polysaccharides. With fruit from a wild tomato (Lycopersicon pimpinellifolium
      [Dunal]) we demonstrated the validity of a nonaqueous fractionation method to
      obtain reliable estimates of the ionic content of the apoplast. In unripe fruit
      no organic acids were associated with the cell wall, which contained 67% of the
      total calcium and 47% of the magnesium. In ripe fruit 4% of the malate, 10% of
      the citrate, and 15% of the oxalate were estimated to be in the cell wall,
      together with 84% of the calcium and 52% of the magnesium. In contrast to the
      cultivated tomato, we did not find a consistent decrease in the degree of methyl
      esterification between unripe and ripe fruit, and an overall average of 75% was
      observed. In the cell walls of ripe fruit the ratio of calcium:magnesium:organic
      acid:unesterified uronic acid, on the basis of charge, was 15:4:4:16. The use of
      a computer program to predict the proportions of different ionic species in
      complex mixtures suggested that in ripe fruit 70% of the unesterified uronic acid
      would be complexed with calcium. Our results show that organic acids do not
      accumulate in the cell wall sufficiently to disrupt calcium cross-linking, nor is
      the calcium removed from the wall into the cell. We therefore conclude that
      organic acids do not contribute to cell separation during the ripening of tomato
      fruit.

PMID- 12228574
TI  - Heat Shock Disrupts Cap and Poly(A) Tail Function during Translation and
      Increases mRNA Stability of Introduced Reporter mRNA.
AB  - The effect of heat shock on translational efficiency and message stability of a
      reporter mRNA was examined in carrot (Daucus carota). Heat shock of short
      duration resulted in an increase in protein yield, whereas repression was
      observed following extended exposure to the stress. Regardless of the duration of
      the heat shock, a loss in the function of the 5[prime] cap
      [m7G(5[prime])ppp(5[prime])N, where N represents any nucleotide] and the 3[prime]
      poly(A) tail, two regulatory elements that work in concert to establish an
      efficient level of translation, was observed. This apparent paradox was resolved
      upon examination of the mRNA half-life following thermal stress, in which
      increases up to 10-fold were observed. Message stability increased as a function
      of the severity of the heat shock so that following a mild to moderate stress the
      increase in message stability more than compensated for the reduction in cap and
      poly(A) tail function. Following a severe heat shock, the increased mRNA half
      life was not sufficient to overcome the virtual loss in cap and poly(A) tail
      function. No stimulation of protein synthesis was observed following a heat shock
      in Chinese hamster ovary cells, data suggesting that the heat-induced increases
      in mRNA stability may be unique to the heat-shock response in plants.

PMID- 12228575
TI  - Differential Solute Regulation in Leaf Blades of Various Ages in Salt-Sensitive
      Wheat and a Salt-Tolerant Wheat x Lophopyrum elongatum (Host) A. Love Amphiploid.
AB  - Leaf blades of different ages from a salt-tolerant wheat x Lophopyrum elongatum
      (Host) A. Love (syn. Agropyron elongatum Host) amphiploid and its salt-sensitive
      wheat parent (Triticum aestivum L.cv Chinese Spring) were compared for their
      ionic relations, organic solute accumulation, and sap osmotic potential
      ([pi]sap). The plants were grown for 18 d in nonsaline (1.25 mM Na+) and
      salinized (200 mM NaCl) nutrient solutions. The response of leaf blades to NaCl
      salinity depended greatly on their age or position on the main stem. Na and
      proline levels were highest in the oldest leaf blade and progressively lower in
      younger ones. Glycine betaine and asparagine levels were highest in the youngest
      blade. The [pi]sap was similar for corresponding leaf blades of both genotypes,
      but contributions of various solutes to the difference in [pi]sap between blades
      from control and 200 mM NaCl treatments differed greatly. The NaCl-induced
      decline in [pi]sap of the youngest leaf blade of Chinese Spring was predominately
      due to the accumulation of Na and to a lesser extent asparagine; in the
      amphiploid, it was due to a combination of glycine betaine, K, Na, and
      asparagine. Proline contributed little in the youngest blade of either genotype.
      In the older blades Na was the major solute contributing to the decline in
      [pi]sap. Thus, the maintenance of low Na and high K levels and the accumulation
      of glycine betaine in the young leaf tissues contributed to the NaCl tolerance of
      the amphiploid. No such role was evident for proline.

PMID- 12228576
TI  - Molecular and Physiological Analysis of a Thylakoid K+ Channel Protein.
AB  - Transport studies identified a K+ channel protein in preparations of purified
      spinach (Spinacea oleracea) thylakoid membrane. This protein was solubilized from
      native membranes and reconstituted into artificial proteoliposomes with
      maintenance of functional integrity. A 33-kD thylakoid polypeptide was identified
      as a putative component of this thylakoid protein. This identification was made
      using an antibody raised against a synthetic peptide representing a highly
      conserved region of K+ channel proteins. K+ channel activity co-migrated with the
      immunoreactive 33-kD polypeptide when solubilized thylakoid membrane protein was
      fractionated on a Suc density gradient. The antibody was used to
      immunoprecipitate the 33-kD polypeptide. Physiological function of this thylakoid
      membrane protein was elucidated by measuring photosynthetic electron transport of
      thylakoid preparations in the presence and absence of a K+ channel blocker.
      Results indicated that K+ efflux from the thylakoid lumen through this channel
      protein is required for the optimization of photosynthetic capacity. The effect
      this protein has on photosynthetic capacity is likely due to the requirement for
      K+ efflux from the thylakoid lumen to charge-balance light-induced proton pumping
      across this membrane.

PMID- 12228578
TI  - How Do Real Roots Work? (Some New Views of Root Structure).

PMID- 12228577
TI  - Salicylic Acid Inhibits Synthesis of Proteinase Inhibitors in Tomato Leaves
      Induced by Systemin and Jasmonic Acid.
AB  - Salicylic acid (SA) and acetylsalicylic acid (ASA), previously shown to inhibit
      proteinase inhibitor synthesis induced by wounding, oligouronides (H.M. Doherty,
      R.R. Selvendran, D.J. Bowles [1988] Physiol Mol Plant Pathol 33: 377-384), and
      linolenic acid (H. Pena-Cortes, T. Albrecht, S. Prat, E.W. Weiler, L. Willmitzer
      [1993] Planta 191: 123-128), are shown here to be potent inhibitors of systemin
      induced and jasmonic acid (JA)-induced synthesis of proteinase inhibitor mRNAs
      and proteins. The inhibition by SA and ASA of proteinase inhibitor synthesis
      induced by systemin and JA, as well as by wounding and oligosaccharide elicitors,
      provides further evidence that both oligosaccharide and polypeptide inducer
      molecules utilize the octadecanoid pathway to signal the activation of proteinase
      inhibitor genes. Tomato (Lycopersicon esculentum) leaves were pulse labeled with
      [35S]methionine, followed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, and the inhibitory effects of SA are shown to be specific for
      the synthesis of a small number of JA-inducible proteins that includes the
      proteinase inhibitors. Previous results have shown that SA inhibits the
      conversion of 13S-hydroperoxy linolenic acid to 12-oxo-phytodienoic acid, thereby
      inhibiting the signaling pathway by blocking synthesis of JA. Here we report that
      the inhibition of synthesis of proteinase inhibitor proteins and mRNAs by SA in
      both light and darkness also occurs at a step in the signal transduction pathway,
      after JA synthesis but preceding transcription of the inhibitor genes.

PMID- 12228579
TI  - Root Architecture and Plant Productivity.

PMID- 12228580
TI  - Cold Acclimation of Arabidopsis thaliana (Effect on Plasma Membrane Lipid
      Composition and Freeze-Induced Lesions).
AB  - Maximum freezing tolerance of Arabidopsis thaliana L. Heyn (Columbia) was
      attained after 1 week of cold acclimation at 2[deg]C. During this time, there
      were significant changes in both the lipid composition of the plasma membrane and
      the freeze-induced lesions that were associated with injury. The proportion of
      phospholipids increased from 46.8 to 57.1 mol% of the total lipids with little
      change in the proportions of the phospholipid classes. Although the proportion of
      di-unsaturated species of phosphatidylcholine and phosphatidylethanolamine
      increased, mono-unsaturated species were still the preponderant species. The
      proportion of cerebrosides decreased from 7.3 to 4.3 mol% with only small changes
      in the proportions of the various molecular species. The proportion of free
      sterols decreased from 37.7 to 31.2 mol%, but there were only small changes in
      the proportions of sterylglucosides and acylated sterylglucosides. Freezing
      tolerance of protoplasts isolated from either nonacclimated or cold-acclimated
      leaves was similar to that of leaves from which the protoplasts were isolated (
      3.5[deg]C for nonacclimated leaves; -10[deg]C for cold-acclimated leaves). In
      protoplasts isolated from nonacclimated leaves, the incidence of expansion
      induced lysis was [less than or equal to]10% at any subzero temperature. Instead,
      freezing injury was associated with formation of the hexagonal II phase in the
      plasma membrane and subtending lamellae. In protoplasts isolated from cold
      acclimated leaves, neither expansion-induced lysis nor freeze-induced formation
      of the hexagonal II phase occurred. Instead, injury was associated with the
      "fracture-jump lesion," which is manifested as localized deviations of the plasma
      membrane fracture plane to subtending lamellae. The relationship between the
      freeze-induced lesions and alterations in the lipid composition of the plasma
      membrane during cold acclimation is discussed.

PMID- 12228581
TI  - Increased Putrescine Biosynthesis through Transfer of Mouse Ornithine
      Decarboxylase cDNA in Carrot Promotes Somatic Embryogenesis.
AB  - Carrot (Daucus carota L.) cells were transformed with Agrobacterium tumefaciens
      strains containing 3[prime]-truncated mouse ornithine decarboxylase (ODC) cDNA
      under the control of a cauliflower mosaic virus 35S promoter. A neomycin
      phosphotransferase gene linked with a nopaline synthase promoter was used to
      select transformed cell lines on kanamycin. Although the nontransformed cells
      contained no ODC, high amounts of mouse-specific ODC activity were observed in
      the transformed cells. Transgenic cells showed a significant increase in the
      cellular content of putrescine compared to control cells. Spermidine, however,
      remained unaffected. Not only did the transformed cells exhibit improved somatic
      embryogenesis in the auxin-free medium, they also regenerated some embryos in the
      presence of inhibitory concentrations of 2,4-dichlorophenoxyacetic acid. These
      cells acquired tolerance to [alpha]-difluoromethylarginine (a potent inhibitor of
      arginine decarboxylase) at concentrations that inhibit growth as well as
      embryogenesis in nontransformed carrot cells, showing that the mouse ODC can
      replace the carrot arginine decarboxylase for putrescine biosynthesis in the
      transgenic cells.

PMID- 12228582
TI  - Purification and Characterization of a Novel Aminopeptidase, Plastidial Alanine
      Aminopeptidase, from the Cotyledons of Etiolated Sugar Beet Seedlings.
AB  - During prolonged dark growth of sugar beet (Beta vulgaris L.) seedlings,
      etioplasts, rapidly after the proplastid-etioplast transition, undergo a
      degenerative process characterized by ultrastructural modifications, protein
      loss, and the decrease of carotenoid and chlorophyll accumulation upon
      illumination. Two plastidial aminopeptidase activities were identified as early
      markers of this degenerative process (A. El Amrani, I. Couee, J.-P. Carde, J.-P.
      Gaudillere, P. Raymond [1994] Plant Physiology 106: 1555-1565). The present study
      focuses on one of these markers and describes the purification to homogeneity and
      characterization of plastidial alanine-aminopeptidase. This novel aminopeptidase
      was found to be a metallo-type naphthylamidase particularly active with alanyl,
      arginyl, and leucyl substrates. Its plastidial location was confirmed by
      immunofluorescence with polyclonal antibodies against the purified enzyme. Its
      physico-chemical and enzymic properties are discussed with respect to other
      higher plant aminopeptidases and to its potential functions during prolonged dark
      growth.

PMID- 12228583
TI  - Differential Transcription of Pea Chloroplast Genes during Light-Induced Leaf
      Development (Continuous Far-Red Light Activates Chloroplast Transcription).
AB  - Plastid gene expression was analyzed in pea (Pisum sativum L.) plants grown in
      darkness, continuous far-red light, and white light. Responses induced by
      continuous far-red light were most likely mediated by PHYA. Plastid transcription
      activity was low in dark-grown plants. In contrast, plastids of plants grown in
      white or far-red light showed a 10-fold increase in transcription activity
      between 4 and 6 d postimbibition (dpi) and a decrease between 6 and 9 dpi.
      Plastid RNAs accumulated in illuminated plants from 5 to 7 dpi. In far-red-light
      illuminated plants, plastid mRNA levels remained elevated until 14 dpi. In white
      light-grown plants, most plastid RNAs decreased in abundance after 7 dpi to very
      low levels by 14 dpi. This indicates that white light induces a general decrease
      in plastid RNA stability compared to far-red-light-illuminated seedlings. PsbA
      mRNA accumulated in older, dark-grown, far-red, and white-light-illuminated
      seedlings, consistent with this RNA having high stability. Transcription of genes
      encoding the plastid's transcription and translation apparatus increased relative
      to rbcL and other genes encoding proteins of the photosynthetic apparatus from 4
      to 5 dpi and then declined 10-fold from 5 to 9 dpi. These data document dynamic
      modulation of plastid gene transcription and mRNA stability during light-induced
      chloroplast development in pea.

PMID- 12228584
TI  - Induction of Hexose-Phosphate Translocator Activity in Spinach Chloroplasts.
AB  - Many environmental and experimental conditions lead to accumulation of
      carbohydrates in photosynthetic tissues. This situation is typically associated
      with major changes in the mRNA and protein complement of the cell, including
      metabolic repression of photosynthetic gene expression, which can be induced by
      feeding carbohydrates directly to leaves. In this study we examined the
      carbohydrate transport properties of chloroplasts isolated from spinach (Spinacia
      oleracea L.) leaves fed with glucose for several days. These chloroplasts contain
      large quantities of starch, can perform photosynthetic 3-phosphoglycerate
      reduction, and surprisingly also have the ability to perform starch synthesis
      from exogenous glucose-6-phosphate (Glc-6-P) both in the light and in darkness,
      similarly to heterotrophic plastids. Glucose-1-phosphate does not act as an
      exogenous precursor for starch synthesis. Light, ATP, and 3-phosphoglyceric acid
      stimulate Glc-6-P-dependent starch synthesis. Short-term uptake experiments
      indicate that a novel Glc-6-P-translocator capacity is present in the envelope
      membrane, exhibiting an apparent Km of 0.54 mM and a Vmax of 2.9 [mu]mol Glc-6-P
      mg-1 chlorophyll h-1. Similar results were obtained with chloroplasts isolated
      from glucose-fed potato leaves and from water-stressed spinach leaves. The
      generally held view that sugar phosphates transported by chloroplasts are
      confined to triose phosphates is not supported by these results. A physiological
      role for a Glc-6-P translocator in green plastids is presented with reference to
      the source/sink function of the leaf.

PMID- 12228585
TI  - A Cytochrome P-450 Monooxygenase Catalyzes the First Step in the Conversion of
      Tabersonine to Vindoline in Catharanthus roseus.
AB  - Hydroxylation at the C-16 position of the indole alkaloid tabersonine has been
      suggested as the first step toward vindoline biosynthesis in Catharanthus roseus.
      Tabersonine 16-hydroxylase (16-OH) activity was detected in total protein
      extracts from young leaves of C. roseus using a novel coupled assay system.
      Enzyme activity was dependent on NADPH and molecular oxygen and was inhibited by
      CO, clotrimazole, miconazole, and cytochrome c. 16-OH was localized to the
      endoplasmic reticulum by linear sucrose density gradient centrifugation. These
      data suggest that 16-OH is a cytochrome P-450-dependent monooxygenase. The
      activity of 16-OH reached a maximum in seedlings 9 d postimbibition and was
      induced by light. The leaf-specific distribution of 16-OH in the mature plant is
      consistent with the localization of other enzymes in the tabersonine to vindoline
      pathway. However, in contrast to enzymes that catalyze the last four steps of
      vindoline biosynthesis, enzymes responsible for the first two steps from
      tabersonine (16-OH and 16-O-methyltransfersase) were detected in C. roseus cell
      suspension cultures. These data complement the complex model of vindoline
      biosynthesis that has evolved with respect to enzyme compartmentalization,
      metabolic transport, and control mechanisms.

PMID- 12228587
TI  - Urease Is Not Essential for Ureide Degradation in Soybean.
AB  - The hypothesis that soybean (Glycine max L. [Merrill]) catabolizes ureides to
      urea to a physiologically significant extent was tested and rejected. Urease
      negative (eu3-e1/eu3-e1) plants were supported by fixed N2 or by 2 mM NH4NO3, so
      that xylem-borne nitrogen contained predominantly ureides (allantoin and
      allantoic acid) or amide amino acids, respectively. Seed nitrogen yield was equal
      on either nitrogen regime, although 35-d-old fixing plants accumulated about 6
      times more leaf urea. In callus, lack of an active urease reduced growth on
      either arginine or allantoin as the sole nitrogen source, but the reduction was
      greater on arginine (73%) than on allantoin (39%). Furthermore, urease-negative
      cells accumulated 17 times more urea than urease-positive cells on arginine; for
      allantoin the ratio was 1.8. Urease-negative callus accumulated urea at 3% the
      rate of seedlings. To test whether urea accumulating in urease-negative seedlings
      was derived from ureides, seeds were first allowed to imbibe in 1 mM allopurinol,
      an inhibitor of ureide formation. Seedling ureides were decreased by 90%, but
      urea levels were unchanged. Thus, ureides are poor precursors of urea, which was
      confirmed in seedlings that converted no more than 5% of seed-absorbed [14C
      ureido]allantoate to [14C]urea, whereas 40 to 70% of [14C-guanido]arginine was
      recovered as [14C]urea.

PMID- 12228586
TI  - Cell-Free Synthesis of Pectin (Identification and Partial Characterization of
      Polygalacturonate 4-[alpha]-Galacturonosyltransferase and Its Products from
      Membrane Preparations of Tobacco Cell-Suspension Cultures).
AB  - Polygalacturonate 4-[alpha]-galacturonosyltransferase (EC 2.4.1.43) activity has
      been identified in microsomal membranes isolated from tobacco (Nicotiana tabacum
      L. cv Samsun) cell-suspension cultures. Incubation of UDP-[14C]galacturonic acid
      with tobacco membranes results in a time-dependent incorporation of
      [14C]galacturonic acid into a chloroform-methanol-precipitable and 65% ethanol
      insoluble product. The optimal synthesis of product occurs at a pH of 7.8, 25 to
      30[deg]C, an apparent Km for UDP-D-galacturonic acid of approximately 8.9 [mu]M,
      and a Vmax of approximately 150 pmol min-1 mg-1 protein. The product was
      characterized by scintillation counting, thin-layer chromatography, high
      performance anion-exchange chromatography, and gel-filtration chromatography in
      combination with enzymatic and chemical treatments. The intact product has a
      molecular mass of approximately 105,000 D based on dextran molecular standards.
      The product was treated with base to hydrolyze ester linkages (e.g. methyl
      esters), digested with a homogeneous endopolygalacturonase (EPGase), or base and
      EPGase treated. Base and EPGase treatment results in cleavage of 34 to 89% of 14C
      labeled product into components that co-chromatograph with mono-, di-, and
      trigalacturonic acid, indicating that a large portion of product contains
      contiguous 1,4-linked [alpha]-D-galactosyluronic acid residues. Optimal EPGase
      fragmentation of the product requires base treatment prior to enzymatic
      digestion, suggesting that 45 to 67% of the galacturonic acid residues in the
      synthesized homogalacturonan are esterified. At least 40% of the base-sensitive
      linkages were shown to be methyl esters by comparing the sensitivity of base
      treated and pectin methylesterase-treated products to fragmentation by EPGase.

PMID- 12228588
TI  - 1-Chloro-2,4-Dinitrobenzene-Elicited Increase in Vacuolar Glutathione-S-Conjugate
      Transport Activity.
AB  - Unlike most other characterized organic solute transport in plants, uptake of the
      model compound S-(2,4-dinitrophenyl)glutathione (DNP-GS) and related glutathione
      S-conjugated by vacuolar membranes is directly energized by MgATP. Here we show
      that exogenous application of the DNP-GS precursor 1-chloro-2,4-dinitrobenzene
      (CDNB) to seedlings of Vigna radiata (mung bean) increases the capacity of
      vacuolar membrane vesicles isolated from hypocotyls for MgATP-dependent DNP-GS
      transport in vitro. Our findings are 4-fold: (a) Pretreatment of seedlings with
      CDNB causes a progressive increase in MgATP-dependent DNP-GS uptake by vacuolar
      membrane vesicles, whereas the same range of CDNB concentrations causes only
      marginal stimulation when the compound benoxacor [4-(dichloroacetyl)-3,4-dihydro
      3-methyl-2H-1,4-benzoxazine] is included in the pretreatment solution. (b)
      Increased DNP-GS uptake is accompanied by a proportionate and selective increase
      in Vmax(DNP-GS) but not in Km(DNP-GS) or Km(MgATP). (c) CDNB-enhanced DNP-GS
      uptake is not accompanied by a change in the density profile or sidedness of the
      vacuolar membrane fraction. (d) Basal and CDNB-enhanced DNP-GS uptake are
      indistinguishable in terms of their inhibitor profiles. On the basis of these
      findings, it is inferred that pretreatment with CDNB increases the amount or
      recruitment of functional transporter into the vacuolar membrane and that agents
      such as benoxacor antagonize the effects otherwise seen with CDNB in this sytem.

PMID- 12228589
TI  - Properties of Proton Pumping in Response to Blue Light and Fusicoccin in Guard
      Cell Protoplasts Isolated from Adaxial Epidermis of Vicia Leaves.
AB  - Guard cell protoplasts (GCPs) were isolated from the adaxial epidermis of Vicia
      leaves. The properties of isolated adaxial GCPs (ad GCPs) were compared with
      those of abaxial GCPs (ab GCPs) with respect to H+-pumping activity. A saturating
      pulse of blue light (200 [mu]mol m-2 s-1, 30 s) induced H+ pumping in both ad
      GCPs and ab GCPs under red light. The maximum rate of blue-light-dependent H+
      pumping was slightly higher in ad GCPs than in ab GCPs, but the magnitude of H+
      pumping in ad GCPs was 68% of that in ab GCPs. H+ pumping was responsive to the
      second pulse, and the rate and magnitude of the pumping increased with the time
      between two pulses. The periods required to achieve 50% of the maximum rate were
      12 and 22 min for ad GCPs and ab GCPs, respectively. The rates of blue-light
      dependent H+ pumping were saturable, with half-saturation at 630 [mu]mol m-2 (21
      [mu]mol m-2 s-1, 30 s) for ad GCPs and 105 [mu]mol m-2 (3.5 [mu]mol m-2 s-1, 30s)
      for ab GCPs. In contrast, fusicoccin, an activator of the plasma membrane H+-
      ATPase, induced H+ pumping with a slightly higher rate in ad GCPs than in ab
      GCPs. Both types of protoplast swelled similarly in response to fusicoccin. These
      results suggest that ad GCPs have almost the same activity for H+ pumping as ab
      GCPs, whereas ad GCPs require a larger number of photons to activate the H+ pump
      than ab GCPs.

PMID- 12228590
TI  - In Vivo Photomodification of Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase
      Holoenzyme by Ultraviolet-B Radiation (Formation of a 66-Kilodalton Variant of
      the Large Subunit).
AB  - Increased levels of solar ultraviolet (290-320 nm) (UV-B) radiation could have
      profound effects on plant proteins because the aromatic amino acids in proteins
      absorb strongly in this spectral region. We have investigated the effects of UV-B
      radiation on plant proteins and have observed a novel 66-kD protein. This product
      was formed in vivo when Brassica napus L. plants grown for 21 d in 65 [mu]mol m-2
      s-1 photosynthetically active radiation were subsequently exposed to 65 [mu]mol m
      2 s-1 photosynthetically active radiation plus UV-B radiation (1.5 [mu]mol m-2 s
      1). The protein appeared after 4 h of UV-B irradiation and accumulated during the
      next 16 h in UV-B. The 66-kD protein cross-reacted with an antiserum against the
      ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) holoenzyme. Analysis of
      soluble leaf proteins revealed that the 66-kD product had a number of isoforms
      corresponding closely to those of the large subunit of Rubisco (LSU). Partial
      proteolytic digests of the LSU and the 66-kD protein resulted in an equivalent
      pattern of protein fragments, leading to the conclusion that the 66-kD protein
      was a photomodified form of the LSU. A similar high molecular mass variant of
      Rubisco was observed in soluble protein extracts from leaves of tomato
      (Lycopersicon esculentum), tobacco (Nicotiana tabacum), and pea (Pisum sativum
      L.) plants treated in vivo with UV-B, suggesting that it might be a common
      product, at least among C3 plants. It is interesting that the 66-kD product
      appears to be generated after incorporation of the LSU into holoenzyme complexes.
      This conclusion was drawn from two lines of evidence. First, the LSU variant co
      purified with holoenzyme complexes isolated by nondenaturing polyacrylamide gel
      electrophoresis. Second, a UV-B-specific 66-kD protein did not accumulate in a
      tobacco mutant that synthesizes the Rubisco subunits but does not assemble them
      into normal holoenzyme complexes.

PMID- 12228591
TI  - Correlated Changes in the Activity, Amount of Protein, and Abundance of
      Transcript of NADPH:Protochlorophyllide Oxidoreductase and Chlorophyll
      Accumulation during Greening of Cucumber Cotyledons.
AB  - Changes in the activity and abundance of NADPH:protochlorophyllide oxidoreductase
      (NPR) and the abundance of mRNA encoding it were examined during the greening of
      5-d-old etiolated cucumber cotyledons under continuous illumination. To measure
      NPR activity in the extracts from fully greened tissues, we have developed an
      improved method of assay. Upon exposure of etiolated cotyledons to light, NPR
      activity decreased rapidly within the first 2 h of exposure. Thereafter,
      enzymatic activity increased transiently, reaching a submaximum level at 12 h,
      and decreased slowly. The level of immunodetectable NPR protein followed the same
      pattern of changes during 96 h of greening as observed for NPR activity. The NPR
      mRNA in etiolated cotyledons disappeared quickly in the 1st h of irradiation.
      However, the level of mRNA increased thereafter to reach 3-fold or more of the
      dark level at 12 h and then decreased. The changes in the activity, protein
      level, and mRNA level after the first rapid decreases corresponded
      chronologically and nearly paralleled the increase in the rate of chlorophyll
      accumulation. These findings suggest that the greening of cucumber cotyledons is
      regulated basically by the level of NPR protein without activation or repression
      of enzymatic activity and that NPR mRNA increased by light maintains the level of
      enzyme protein necessary for greening.

PMID- 12228592
TI  - Morphological and Molecular Characteristics of Host-Conditioned Ineffective Root
      Nodules in Cowpea.
AB  - In cowpea (Vigna unguiculata [L.] Walp.) a recessive allele, designated cpi,
      elicits the formation of non-N2-fixing nodules with all bacterial isolates
      tested. Comparisons of mutant and wild-type nodules demonstrated that the
      ineffective nodules were anatomically similar to the wild type and contained both
      infection threads and bacteroids. Ineffective nodules were smaller, however,
      largely because of the reduced size of the infected cells. Additionally, the
      number of bacteroids was reduced and senescence occurred prematurely in the
      infected cells. Grafting studies demonstrated that the defect in nodule
      development was controlled by the root rather than the shoot. Northern analysis
      of four nodulin genes indicated that in the ineffective nodules transcript levels
      of the early nodulin VuENOD2 were initially reduced but were equivalent to wild
      type nodules by 21 d. In contrast, transcript levels of the early nodulin VuB
      were initially similar in both genotypes but as the nodules matured the mRNA
      levels declined more slowly in the ineffective nodules. The late nodulins
      leghemoglobin and uricase were expressed in the ineffective nodules but at
      greatly reduced levels. Thus, the cpi-conditioned defect in nodulation is
      associated with impaired bacteroid maturation and maintenance, altered nodulin
      expression, and accelerated senescence.

PMID- 12228593
TI  - Ferric Leghemoglobin in Plant-Attached Leguminous Nodules.
AB  - Leghemoglobin (Lb) is essential for nitrogen fixation by intact leguminous
      nodules. To determine whether ferric Lb (Lb3+) was detectable in nodules under
      normal or stressed conditions, we monitored the status of Lb in intact nodules
      attached to sweet clover (Melilotus officinalis) and soybean (Glycine max [L.]
      Merr.) roots exposed to various conditions. The effects of N2 and O2 streams and
      elevated nicotinate levels on root-attached nodules were tested to determine
      whether the spectrophotometric technique was showing the predicted responses of
      Lb. The soybean and sweet clover nodules' Lb spectra indicated predominantly
      ferrous Lb and LbO2 in young (34 d) plants. As the nodule aged beyond 45 d, it
      was possible to induce Lb3+ with a 100% O2 stream (15 min). At 65 d without
      inducement, the nodule Lb status indicated the presence of some Lb3+ along with
      ferrous Lb and oxyferrous Lb. Nicotinate and fluoride were used as ligands to
      identify Lb3+. Computer-calculated difference spectra were used to demonstrate
      the changes in Lb spectra under different conditions. Some conditions that
      increased absorbance in the 626 nm region (indicating Lb3+ accumulation) were
      root-fed ascorbate and dehydroascorbate, plant exposure to darkness, and nodule
      water immersion.

PMID- 12228594
TI  - Changes in Protein Isoprenylation during the Growth of Suspension-Cultured
      Tobacco Cells.
AB  - Isoprenylation facilitates the association of proteins with intracellular
      membranes and/or other proteins. In mammalian and yeast cells, isoprenylated
      proteins are involved in signal transduction, cell division, organization of the
      cytoskeleton, and vesicular transport. Recently, protein isoprenylation has been
      demonstrated in higher plants, but little is currently known about the functions
      of isoprenylated plant proteins. We report that inhibitors of 3-hydroxy-3
      methylglutaryl coenzyme A reductase (lovastatin) or prenyl:protein transferases
      (perilly alcohol) severely impair the growth of cultured tobacco (Nicotiana
      tabacum) cells but only when added within the first 2 d following transfer to
      fresh medium, before any increase in culture volume is detectable. This "window"
      of sensitivity to inhibitors of protein isoprenylation correlates temporally with
      an increase in [14C]mevalonate incorporation into tobacco cell proteins in vitro.
      We have also observed a marked increase in farnesyl:protein transferase activity
      at this early time in the growth of tobacco cultures. In contrast, type I
      geranylgeranyl:protein transferase activity does not change significantly during
      culture growth. Although these events coincide with the replication of DNA, I
      [mu]M lovastatin-treated cells are capable of DNA synthesis, suggesting that
      lovastatin-induced cell growth arrest is not due to inhibition of DNA
      replication. Together, these data support the hypothesis that protein
      isoprenylation is necessary for the early stages of growth of tobacco cultures.

PMID- 12228595
TI  - The Tonoplast H+-ATPase of Acer pseudoplatanus Is a Vacuolar-Type ATPase That
      Operates with a Phosphoenzyme Intermediate.
AB  - The tonoplast H+-ATPase of Acer pseudoplatanus has been purified from isolated
      vacuoles. After solubilization, the purification procedure included size
      exclusion and ion-exchange chromatography. The H+-ATPase consists of at least
      eight subunits, of 95, 66, 56, 54, 40, 38, 31, and 16 kD, that did not cross
      react with polyclonal antibodies raised to the plasmalemma ATPase of Arabidopsis
      thaliana. The 66-kD polypeptide cross-reacted with monoclonal antibodies raised
      to the 70-kD subunit of the vacuolar H+-ATPase of oat roots. The functional
      molecular size of the tonoplast H+-ATPase, analyzed in situ by radiation
      inactivation, was found to be around 400 kD. The 66-kD subunit of the tonoplast
      H+-ATPase was rapidly phosphorylated by [[gamma]-32P]ATP in vitro. The complete
      loss of radio-activity in the 66-kD subunit after a short pulse-chase experiment
      with unlabeled ATP reflected a rapid turnover, which characterizes a
      phosphorylated intermediate. Phosphoenzyme formed from ATP is an acylphosphate
      type compound as shown by its sensitivity to hydroxylamine and alkaline pH. These
      results lead us to suggest that the tonoplast H+-ATPase of A. pseudoplatanus is a
      vacuolar-type ATPase that could operate with a plasmalemma-type ATPase catalytic
      mechanism.

PMID- 12228596
TI  - Glucosinolate Biosynthesis (Further Characterization of the Aldoxime-Forming
      Microsomal Monooxygenases in Oilseed Rape Leaves).
AB  - The initial steps in glucosinolate biosynthesis are thought to proceed from amino
      acids, via N-hydroxy amino acids, to aldoximes. We showed previously that
      microsomes from green leaves of oilseed rape (Brassica napus cv Bienvenu) contain
      two distinct monooxygenases that catalyze the conversion of homophenylalanine and
      dihomomethionine to their respective aldoximes. Further characterization of these
      enzymes has now demonstrated that the latter enzyme catalyzes the NADPH-dependent
      oxidative decarboxylation of two higher homologs of methionine, in addition to
      dihomomethionine. No activity was found for either enzyme with L-methionine, DL
      homomethionine, L-phenylalanine, L-tyrosine, or L-tryptophan. Both of these rape
      monooxygenase activities are dependent on O2, not requiring any other O2 species
      or radical. The presence of an unoxidized sulfur atom and its relative position
      in the side chain of the aliphatic substrates are important for binding to the
      active site of the methionine-homolog enzyme. Neither enzyme has any
      characteristics of a cytochrome P450-type enzyme, and antiserum raised against
      cytochrome P450 reductase did not significantly inhibit monooxygenase activity.

PMID- 12228597
TI  - Regulation of Photosynthetic Induction State in High- and Low-Light-Grown Soybean
      and Alocasia macrorrhiza (L.) G. Don.
AB  - Alocasia (Alocasia macrorrhiza [L.] G. Don) and soybean (Glycine max [L.]) were
      grown under high or low photon flux density (PFD) conditions to achieve a range
      of photosynthetic capacities and light-adaptation modes. The CO2 assimilation
      rate and in vivo linear electron transport rate (Jf) were determined over a range
      of PFDs and under saturating 1-s-duration lightflecks applied at a range of
      frequencies. At the same mean PFD, the assimilation rate and the Jf were lower
      under the lightfleck regimes than under constant light. The activation state of
      two, key enzymes of the photosynthetic carbon reduction cycle pathway, ribulose
      1,5-bisphosphate carboxylase/oxygenase (Rubisco) and fructose-1,6-bisphosphatase,
      and the photosynthetic induction states (ISs) were also found to be lower under
      flashing as compared to continuous PFD. Under all conditions, the IS measured 120
      s after an increase in PFD to constant and saturating values was highly
      correlated with the Rubisco activation state and stomatal conductances
      established in the light regime before the increase. Both the fructose-1,6
      bisphosphatase and Rubisco activities established in a particular light regime
      were highly correlated with the mean Jf in that regime. The relationships between
      enzyme activation state and Jf and between IS and enzyme activation state were
      similar in soybean and Alocasia and were not affected either by growth-light
      regime, and hence photosynthetic capacity, or by flashing versus constant PFD.
      The common relationship between the linear Jf and the activation state of key
      enzymes suggests that electron transport may be the determinant of the signal
      regulating IS, at least to the extent that the IS is controlled by the activation
      state of key stromal enzymes.

PMID- 12228598
TI  - Kinetics of NO3- Influx in Spruce.
AB  - Influxes of 13NO3- across the root plasmalemma were measured in intact seedlings
      of Picea glauca (Moench) Voss. Three kinetically distinct uptake systems for NO3-
      were identified. In seedlings not previously exposed to external NO3-, a single
      Michaelis-Menten-type constitutive high-affinity transport system (CHATS)
      operated in a 2.5 to 500 [mu]M range of external NO3- [NO3-]o. The Vmax of this
      system was 0.1 [mu]mol g-1 h-1, and the Km was approximately 15 [mu]M. Following
      exposure to NO3- for 3 d, this CHATS activity was increased approximately 3-fold,
      with no change of Km. In addition, a NO3--inducible high-affinity system became
      apparent with a Km of approximately 100[mu]M. The combined Vmax for these
      discrete saturable components was 0.7 [mu]mol g-1 h-1. In both uninduced and
      induced plants a linear low-affinity system, additive to CHATS and an NO3-
      inducible high-affinity system, operated at [NO3-]o [greater than or equal to] 1
      mM. The time taken to achieve maximal rates of uptake (full induction) was 2 d
      from 1.5 mM [NO3-]o and 3 d from 200 [mu]M [NO3-]o.

PMID- 12228599
TI  - Effects of Mercuric Chloride on the Hydraulic Conductivity of Tomato Root Systems
      (Evidence for a Channel-Mediated Water Pathway).
AB  - A pressure-flux approach was used to evaluate the effects of HgCl2 on water
      transport in tomato (Lycopersicon esculentum) roots. Addition of HgCl2 to a root
      bathing solution caused a large and rapid reduction in pressure-induced root
      water flux; the inhibition was largely reversible upon addition of [beta]
      mercaptoethanol. Root system hydraulic conductivity was reduced by 57%. There was
      no difference between treatments in the K+ concentration in xylem exudate. The
      results are consistent with the presence of a protein-mediated path for
      transmembrane water flow in tomato roots.

PMID- 12228600
TI  - Alternative Oxidase Activity in Tobacco Leaf Mitochondria (Dependence on
      Tricarboxylic Acid Cycle-Mediated Redox Regulation and Pyruvate Activation).
AB  - Transgenic Nicotiana tabacum (cv Petit Havana SR1) containing high levels of
      mitochondrial alternative oxidase (AOX) protein due to the introduction of a
      sense transgene(s) of Aox1, the nuclear gene encoding AOX, were used to
      investigate mechanisms regulating AOX activity. After purification of leaf
      mitochondria, a large proportion of the AOX protein was present as the oxidized
      (covalently associated and less active) dimer. High AOX activity in these
      mitochondria was dependent on both reduction of the protein by DTT (to the
      noncovalently associated and more active dimer) and its subsequent activation by
      certain [alpha]-keto acids, particularly pyruvate. Reduction of AOX to its more
      active form could also be mediated by intramitochondrial reducing power generated
      by the oxidation of certain tricarboxylic acid cycle substrates, most notably
      isocitrate and malate. Our evidence suggests that NADPH may be specifically
      required for AOX reduction. All of the above regulatory mechanisms applied to AOX
      in wild-type mitochondria as well. Transgenic leaves lacking AOX due to the
      introduction of an Aox1 antisense transgene or multiple sense transgenes were
      used to investigate the potential physiological significance of the AOX
      regulatory mechanisms. Under conditions in which respiratory carbon metabolism is
      restricted by the capacity of mitochondrial electron transport, feed-forward
      activation of AOX by mitochondrial reducing power and pyruvate may act to prevent
      redirection of carbon metabolism, such as to fermentative pathways.

PMID- 12228601
TI  - The Biochemical Response of Electrical Signaling in the Reproductive System of
      Hibiscus Plants.
AB  - Stimulation of the stigma of Hibiscus flowers by pollen, wounding (heat), or cold
      shock (4[deg]C) evokes electrical potential changes in the style, which propagate
      toward the ovary with a speed of 1.3 to 3.5 cm s-1. Potential changes were
      measured intracellularly by microelectrodes inserted in the style. The resting
      potential ranged from -90 to -112 mV (n = 20) in cells of the vascular tissue and
      from -184 to -220 mV (n = 22) in cells of the pollen-transmitting tissue. The
      amplitude of the potential changes was between 40 and 150 mV, depending on the
      kind of stimulus. Self- as well as cross-pollination hyperpolarized the resting
      potential after 50 to 100 s, followed by a series of 10 to 15 action potentials.
      In contrast, cooling of the stigma caused a single action potential with a
      different shape and duration, whereas wounding generated a strong depolarization
      of the membrane potential with an irregular form and a lower transmission rate.
      To determine the physiological function of the different signals measured in the
      style, the gas exchange and metabolite concentrations were measured in the ovary
      before and 10 min after stimulation of the stigma. Self- and cross-pollination
      caused a transient increase of the ovarian respiration rate by 12%, which was
      measured 3 to 5 min after the stigma was stimulated. Simultaneously, the levels
      of ATP, ADP, and starch increased significantly. In contrast, both cold shock and
      wounding of the stigma caused a spontaneous decrease of the CO2 content in the
      measuring chamber, as well as reduced metabolite concentrations in the ovary.
      Since the transport of labeled auxin from the top to the base of the style lasts
      at least 45 min, the influence of a chemical substance transmitted within 10 min
      is unlikely. Thus, our results strongly support the view that different, stimulus
      dependent electrical signals cause specific responses of the ovarian metabolism.

PMID- 12228602
TI  - Microsomal Lyso-Phosphatidic Acid Acyltransferase from a Brassica oleracea
      Cultivar Incorporates Erucic Acid into the sn-2 Position of Seed
      Triacylglycerols.
AB  - Developing seeds from Brassica oleracea (L.) var botrytis cv Sesam were examined
      for the ability to biosynthesize and incorporate erucic acid into
      triacylglycerols (TAGs). Seed embryos at mid-development contained a high
      concentration of erucic acid in diacylglycerols and TAGs, and substantial levels
      were also detected in free fatty acids, acyl-coenzyme A (CoA), phosphatidic acid,
      and phosphatidylcholine. Homogenates and microsomal fractions from seeds at mid
      development produced [14C]eicosenoyl- and [14C]erucoyl-CoAs from [14C]oleoyl-CoA
      in the presence of malonyl-CoA and reducing equivalents in vitro. These fatty
      acids were incorporated into TAGs via the Kennedy pathway. However, unlike most
      Brassicaceae, the B. oleracea was able to insert significant erucic acid into the
      sn-2 position of TAGs. It was shown that the lyso-phosphatidic acid
      acyltransferase (LPAT) incorporated erucic acid into the sn-2 position of lyso
      phosphatidic acid. The erucoyl-CoA:LPAT activity during seed development and the
      sn-2 erucic acid content of the TAG fraction in mature seed were compared to
      those in B. napus, Tropaeolum majus, and Limnanthes douglasii. There was a
      correlation between the in vitro erucoyl-CoA:LPAT activity and the sn-2 erucic
      acid content in seed TAGs. To our knowledge, this is the first member of the
      Brassicaceae reported to have an LPAT able to use erucoyl-CoA. This observation
      has important implications for efforts being made to increase the erucic acid
      content in B. napus, to supply strategic industrial feedstocks.

PMID- 12228603
TI  - Amelioration of Ozone-Induced Oxidative Damage in Wheat Plants Grown under High
      Carbon Dioxide (Role of Antioxidant Enzymes).
AB  - O3-induced changes in growth, oxidative damage to protein, and specific
      activities of certain antioxidant enzymes were investigated in wheat plants
      (Triticum aestivum L. cv Roblin) grown under ambient or high CO2. High CO2
      enhanced shoot biomass of wheat plants, whereas O3 exposure decreased shoot
      biomass. The shoot biomass was relatively unaffected in plants grown under a
      combination of high CO2 and O3. O3 exposure under ambient CO2 decreased
      photosynthetic pigments, soluble proteins, and ribulose-1,5-bisphosphate
      carboxylase/oxygenase protein and enhanced oxidative damage to proteins, but
      these effects were not observed in plants exposed to O3 under high CO2. O3
      exposure initially enhanced the specific activities of superoxide dismutase,
      peroxidase, glutathione reductase, and ascorbate peroxidase irrespective of
      growth in ambient or high CO2. However, the specific activities decreased in
      plants with prolonged exposure to O3 under ambient CO2 but not in plants exposed
      to O3 under high CO2. Native gels revealed preferential changes in the isoform
      composition of superoxide dismutase, peroxidases, and ascorbate peroxidase of
      plants grown under a combination of high CO2 and O3. Furthermore, growth under
      high CO2 and O3 led to the synthesis of one new isoform of glutathione reductase.
      This could explain why plants grown under a combination of high CO2 and O3 are
      capable of resisting O3-induced damage to growth and proteins compared to plants
      exposed to O3 under ambient CO2.

PMID- 12228604
TI  - Differential Expression of Proteins and mRNAs from Border Cells and Root Tips of
      Pea.
AB  - Many plants release large numbers of metabolically active root border cells into
      the rhizosphere. We have proposed that border cells, cells produced by the root
      cap meristem that separate from the rest of the root upon reaching the periphery
      of the cap, are a singularly differentiated part of the root system that
      modulates the environment of the plant root by producing specific substances to
      be released into the rhizosphere. Proteins synthesized in border cells exhibit
      profiles that are very distinct from those of the root tip (root cap, root
      meristem, and adjacent cells). In vivo-labeling experiments demonstrate that 13%
      of the proteins that are abundant in preparations from border cells are
      undetectable in root tip preparations. Twenty-five percent of the proteins
      synthesized by border cells in a 1-h period are rapidly excreted into the
      incubation medium. Quantitative variation in levels of specific marker proteins,
      including glutamine synthetase, heat-shock protein 70, and isoflavone reductase,
      also occurs between border cells and cells in the root tip. mRNA differential
      display assays demonstrate that these large qualitative and quantitative
      differences in protein expression are correlated with similarly distinct patterns
      of gene expression. These observations are consistent with the hypothesis that a
      major switch in gene expression accompanies differentiation into root border
      cells, as expected for cells with specialized functions in plant development.

PMID- 12228606
TI  - Analysis of 13NH4+ Efflux in Spruce Roots (A Test Case for Phase Identification
      in Compartmental Analysis).
AB  - 13NH4+-efflux analyses were conducted with roots of intact Picea glauca (Moench)
      Voss. seedlings at external NH4+ concentrations of 100 [mu]M and 1.5 mM. Three
      kinetically distinct phases were identified with half-lives of exchange of
      approximately 2 s, 30 s, and 14 min. The presumed identities of the subcellular
      compartments corresponding to these phases were confirmed by several techniques,
      including pretreatment of roots (a) at 75[deg]C or with SDS, (b) with [alpha]
      keto-glutarate or L-methionine-DL-sulfoximine, (c) at elevated levels of Ca2+,
      and (d) at low pH or with Al3+ at low pH. Treatments a and b selectively
      influenced phase III without affecting phases I and II. Similarly, treatment c
      selectively perturbed phase II, and treatment d affected phases II and III. Based
      on these findings and the assumption of an in-series arrangement of root cell
      compartments, it was concluded that phase III corresponded to the cytoplasm,
      phase II corresponded to the Donnan free space, and phase I corresponded to a
      film of solution adhering to the root surface.

PMID- 12228605
TI  - Blue-Light-Regulated Expression of Genes for Two Early Steps of Chlorophyll
      Biosynthesis in Chlamydomonas reinhardtii.
AB  - In light:dark-synchronized cultures of Chlamydomonas reinhardtii, the genes
      encoding the enzymes for two early steps of chlorophyll biosynthesis, glutamate-1
      semialdehyde aminotransferase (gsa) and [delta]-aminolevulinic acid dehydratase
      (alad), are expressed at high levels early in the light phase, just prior to a
      rapid burst of chlorophyll synthesis. Induction of gsa mRNA in synchronized cells
      is totally dependent on light, whereas induction of alad mRNA occurs to
      approximately one-half the light-induced level even in cells kept in the dark
      during the light phase and appears to be dependent on the cell cycle or a
      circadian rhythm. gsa mRNA and alad mRNA accumulation is induced by light that
      was passed through blue (400-480 nm) or green (490-590 nm) filters but not by
      light that was passed through orange (>560 nm) or red (>610 nm) filters,
      indicating the participation of a blue-light photoreceptor system rather than a
      protochlorophyllide- or rhodopsin-based photoreceptor. Light induction of gsa
      mRNA accumulation is absent in a carotenoid-deficient mutant, which suggests that
      a carotenoid-containing blue-light photoreceptor is involved. In contrast,
      pretreatment of wild-type cells with either of two flavin antagonists,
      phenylacetic acid and KI, does not prevent the light induction. In the later part
      of the light phase, the gsa mRNA level decreases more rapidly than that of alad
      mRNA. Turnover studies indicate that the half-life of alad mRNA is twice that of
      gsa mRNA. This difference in mRNA stability partially accounts for the more rapid
      decline in gsa mRNA levels after the peak of light induction is reached. Thus,
      differential blue-light induction and stability of mRNAs regulates the expression
      of these two chlorophyll biosynthetic genes.

PMID- 12228607
TI  - Induction of Stomatal Closure by Vanadate or a Light/Dark Transition Involves
      Ca2+-Calmodulin-Dependent Protein Phosphorylations.
AB  - Previous studies indicate that a continual source of adenosine 5[prime]
      triphosphate is required for both opening and closing of stomata. However,
      vanadate (Na3VO4 at 500 [mu]M) as well as a light/dark transition induced
      stomatal closing in epidermal peels of Commelina communis L., showing that the
      stoppage or even the decrease of the activity of the plasma membrane H+-adenosine
      5[prime]-triphosphatase is sufficient to induce stomatal closure. Furthermore,
      stomatal closing in response to Na3VO4 or a light/dark transition was suppressed
      by inhibitors of metabolism (10 [mu]M carbonyl cyanide m-chlorophenylhydrazone)
      and of protein kinases (20 [mu]M 1-[5-iodonaphthalene-1-sulfonyl]-1H-hexa-hydro
      1,4-diaz-epine), calmodulin antagonists (20 [mu]M N-[6-aminohexyl]-5-chloro-1
      naphthalenesulfonamide), and the anion channel blocker 5-nitro-2,3
      phenylpropyllamino benzoic acid (50 [mu]M). These data suggest that the slow,
      outward rectifying anion channel, whose opening would be related to the membrane
      potential, and at least one step requiring a protein phosphorylation by a Ca2+
      calmodulin-dependent protein kinase of the myosin light chain kinase type might
      be implicated in the induction of stomatal closing by vanadate or a light/dark
      transition.

PMID- 12228608
TI  - [beta]-Tubulin Accumulation and DNA Replication in Imbibing Tomato Seeds.
AB  - The activation of the cell cycle in embryo root tips of imbibing tomato
      (Lycopersicon esculentum Mill. cv Lerica) seeds was studied by flow cytometric
      analyses of the nuclear DNA content and by immunodelection of [beta]-tubulin.
      With dry seeds, flow cytometric profiles indicated that the majority of the cells
      were arrested at the G1 phase of the cell cycle. In addition, [beta]-tubulin was
      not detectable on western blots. Upon imbibition of water, the number of cells in
      G2 started to increase after 24 h, and a 55-kD [beta]-tubulin signal was detected
      between 24 and 48 h. Two-dimensional immunoblots revealed at least three
      different [beta]-tubulin isotypes. Thus, [beta]-tubulin accumulation and DNA
      replication were induced during osmotic priming. These processes, as well as seed
      germination rate, were enhanced upon subsequent imbibition of water, compared
      with control seeds that imbibed but were not primed. By contrast, when aged seeds
      imbibed, DNA replication, [beta]-tubulin accumulation, and germination were
      delayed. In all cases studied, both DNA replication and [beta]-tubulin
      accumulation preceded visible germination. We suggest that activation of these
      cell-cycle-related processes is a prerequisite for tomato seed germination.
      Furthermore, [beta]-tubulin expression can be used as a parameter for following
      the initial processes that are activated during seed imbibition.

PMID- 12228609
TI  - Identification of an N-Glucoside of cis-Zeatin from Potato Tuber Sprouts.
AB  - A compound was isolated from potato (Solanum tuberosum L. cv Bintje) tuber
      sprouts by immunoaffinity chromatography with antibodies against the cytokinins
      zeatin riboside and isopentenyladenosine. Analysis by ultraviolet spectroscopy
      and gas chromatography-mass spectrometry of derivatives identified the compound
      as a 9-glucoside of 6-[(Z)-4-hydroxy-3-methyl-2-butenylamino]purine (cis-zeatin).
      N-glucosides have often been reported as metabolites of other cytokinins, but to
      our knowledge, they have never before been found for cis-zeatin. The finding
      gives proof that cis-zeatin, a modified base in tRNA, also exists as a free
      substance in plants, since the glucoside, unlike other tRNA-free cis-zeatins
      described earlier by others, cannot arise by enzymatic degradation of tRNA during
      plant extraction.

PMID- 12228610
TI  - Light Alters Cytosolic and Plastidic Phosphorylase Distribution in Pearl Millet
      Leaves.
AB  - In pearl millet (Pennisetum americanum) seedlings, although the cytosolic
      phosphorylase was present in all organs, the plastidic phosphorylase was
      restricted to the leaf. Intercellular fractionation of the leaf revealed that
      cytosolic and plastidic phosphorylase were localized in the mesophyll and bundle
      sheath cells, respectively. In dark-grown leaves phosphorylase activity increased
      from the leaf base to the tip. The dark-grown leaves possessed both cytosolic and
      plastidic phosphorylase isoforms; however, their distribution followed different
      patterns along the length of the leaf. The plastidic phosphorylase level
      increased from the base to the tip of the leaf, and the cytosolic phosphorylase
      level was higher in the basal half of the leaf and declined toward the tip. In
      light-grown leaves phosphorylase activity was higher in a region near the leaf
      base and declined toward the leaf tip. Light stimulated cytosolic phosphorylase
      level and repressed plastidic phosphorylase level, resulting in an altered
      distribution of the respective phosphorylase isoforms along the length of the
      light-grown leaf. Since pearl millet leaf possesses a cell maturity and
      chloroplast development gradient from the leaf base to the tip, the inverse
      effect of light on cytosolic and plastidic phosphorylase levels might have been
      determined by its interaction with these gradients.

PMID- 12228611
TI  - Tonoplast Na+/H+ Antiport Activity and Its Energization by the Vacuolar H+-ATPase
      in the Halophytic Plant Mesembryanthemum crystallinum L.
AB  - Tonoplast vesicles were isolated from leaf mesophyll tissue of the inducible
      Crassulacean acid metabolism plant Mesembryanthemum crystallinum to investigate
      the mechanism of vacuolar Na+ accumulation in this halophilic species. In 8-week
      old plants exposed to 200 mM NaCl for 2 weeks, tonoplast H+-ATPase activity was
      approximately doubled compared with control plants of the same age, as determined
      by rates of both ATP hydrolysis and ATP-dependent H+ transport. Evidence was also
      obtained for the presence of an electroneutral Na+/H+ antiporter at the tonoplast
      that is constitutively expressed, since extravesicular Na+ was able to dissipate
      a pre-existing transmembrane pH gradient. Initial rates of H+ efflux showed
      saturation kinetics with respect to extravesicular Na+ concentration and were 2.1
      fold higher from vesicles of salt-treated plants compared with the controls. Na+
      dependent H+ efflux also showed a high selectivity for Na+ over K+, was
      insensitive to the transmembrane electrical potential difference, and was more
      than 50% inhibited by 200 [mu]M N-amidino-3,5-diamino-6-chloropyrazinecarboxamide
      hydrochloride. The close correlation between increased Na+/H+ antiport and H+
      ATPase activities in response to salt treatment suggests that accumulation of the
      very high concentrations of vacuolar Na+ found in M. crystallinum is energized by
      the H+ electrochemical gradient across the tonoplast.

PMID- 12228612
TI  - Onset of Phloem Export from Senescent Petals of Daylily.
AB  - During senescence, petals of attached daylily (Hemerocallis hybrid cv Cradle
      Song) flowers lost 95% sugar and 65% dry weight over the first 24 h, with 30% of
      dry weight loss coming from nonsugar components. Detaching flowers did not delay
      senescence, but halted loss of carbohydrate and amino acid, suggesting that loss
      in the intact state was due to phloem export. Petal autolysis occurred mainly in
      the interveinal parenchyma, causing vascular strands to begin separating from the
      petal mass. Such vascular strands still stained with tetrazolium and accumulated
      sucrose, indicating a retained viability. Their sucrose accumulation rates were
      high in comparison with those of other plant tissues, and the accumulated product
      was mainly sucrose. Sucrose synthesis took place in the senescent petal, and
      sucrose was the principal sugar in phloem exudate, whereas hydroxyproline and
      glutamine were the main transport amino acids. [14C]Sucrose applied to attached
      senescent flowers was rapidly translocated to other parts of the plant,
      particularly developing flower buds. Thus, onset of phloem export allowed most of
      the soluble carbohydrate and amino acid in the senescing flower to be retrieved
      by the plant. Additional salvaged material came from proteins and possibly from
      structural carbohydrate. Over a 12-h period, the flower switched from acting as a
      strong carbohydrate sink during expansion to become a strong source during
      senescence. This rapid reversal offers potential for phloem transport studies.

PMID- 12228613
TI  - Auxin-Modulated Protein Disulfide-Thiol-Interchange Activity from Soybean Plasma
      Membranes.
AB  - The renaturation of scrambled (oxidized and inactive) RNase A is catalyzed by
      soybean (Glycine max cv Williams 82) plasma membranes. The catalysis is
      stimulated by the auxin herbicide 2,4-dichlorophenoxyacetic acid or by the
      natural auxin indole-3-acetic acid. The inactive auxin analog, 2,3
      dichlorophenoxyacetic acid, is without effect. The activity occurs in the absence
      of external electron acceptors or donors and therefore appears to be a true
      disulfide-thiol-interchange activity between protein disulfides and thiols of
      RNase A and those of plasma membrane proteins. The activity is not affected by a
      mixture of reduced and oxidized glutathione. However, no auxin-stimulated
      activity was observed in the presence of either oxidized glutathione or reduced
      glutathione alone, a response characteristic of the previously described auxin
      stimulated NADH oxidase activity of soybean plasma membranes. Taken together, the
      results suggest the operation in the plant plasma membrane of a protein disulfide
      thiol-interchange activity that is stimulated by auxins. The auxin stimulations
      of the interchange activity are prevented by glutathione, reduced glutathione,
      and brefeldin A at concentrations that also prevent auxin stimulation of NADH
      oxidation by isolated plasma membranes and inhibit, as well, the auxin-stimulated
      elongation of excised segments of soybean hypocotyls.

PMID- 12228614
TI  - Sucrose Release into the Endosperm Cavity of Wheat Grains Apparently Occurs by
      Facilitated Diffusion across the Nucellar Cell Membranes.
AB  - Nutrients required for the growth of the embryo and endosperm of developing wheat
      (Triticum aestivum L.) grains are released into the endosperm cavity from the
      maternal tissues across the nucellar cell plasma membranes. We followed the
      uptake and efflux of sugars into and out of the nucellus by slicing grains
      longitudinally through the endosperm cavity to expose the nucellar surface to
      experimental solutions. Sucrose uptake and efflux are passive processes. Neither
      was sensitive to metabolic inhibitors, pH, or potassium concentration. p
      Chloromercuribenzene sulfonate, however, strongly inhibited both uptake and
      efflux, although not equally. Except for p-chloromercuribenzene sensitivity,
      these characteristics of efflux and the insensitivity of Suc movement to turgor
      pressure are similar to those of sucrose release from maize pedicels, but they
      contrast with legume seed coats. Although the evidence is incomplete, movement
      appears to be carrier mediated rather than channel mediated. In vitro rates of
      sucrose efflux were similar to or somewhat less than in vivo rates, suggesting
      that transport across the nucellar cell membranes could be a factor in the
      control of assimilate import into the grain.

PMID- 12228615
TI  - Sucrose Concentration Gradients along the Post-Phloem Transport Pathway in the
      Maternal Tissues of Developing Wheat Grains.
AB  - Sucrose concentrations were measured in serial frozen sections of the post-phloem
      transport pathway in developing wheat (Triticum aestivum L.) grains. In normally
      importing grains, there was an approximately linear concentration gradient along
      the pathway, with a difference between the ends of the pathway of about 180 mM.
      This indicates an unusually low resistance for cell-to-cell transport, due
      perhaps to the large size-exclusion limit for the pathway. However, the existence
      of concentration gradients raises presently unresolvable questions about the
      relative contributions of diffusion versus bulk flow to transport within the
      symplast. The concentration gradient disappeared when sucrose movement ceased
      (i.e. in excised grains or when endosperm cavities of attached grains were
      perfused with p-chloromercuribenzene sulfonate [PCMBS] or with 1660 mOsm
      sorbitol). PCMBS appeared to block solute release into the endosperm cavity,
      whereas the sorbitol treatment, previously shown to cause localized plasmolysis
      in the chalaza, appeared to block movement across the chalaza. Sieve
      element/companion cell unloading appears to be an important control point for
      assimilate import. The sucrose concentration gradient and, probably, turgor and
      osmotic gradients are extremely steep there. PCMBS blocked import without
      affecting the sucrose concentration in the vascular parenchyma around the phloem.
      Thus, blockage of unloading was more complex than a simple "backing up" of
      solutes in the vascular parenchyma.

PMID- 12228616
TI  - Translatable RNA Populations Associated with Maintenance of Primary Root
      Elongation and Inhibition of Mesocotyl Elongation by Abscisic Acid in Maize
      Seedlings at Low Water Potentials.
AB  - Previous work indicated that accumulation of abscisic acid (ABA) acts
      differentially to maintain elongation of the primary root and inhibit elongation
      of the mesocotyl of maize (Zea mays L.) seedlings at low water potentials
      ([psi]w). Subsequent results indicated specific locations in the elongation zones
      where elongation is maintained, inhibited, or unaffected by endogenous ABA at low
      [psi]w. This information was utilized in this study to identify in vitro
      translation products of RNA associated with the maintenance or inhibition of
      elongation in the primary root and mesocotyl, respectively, by endogenous ABA at
      low [psi]w. The results distinguished products associated specifically with the
      elongation responses from those nonspecifically associated with ABA accumulation
      or low [psi]w, as well as normal cell development and maturation. In the primary
      root, the maintenance of elongation at low [psi]w by ABA was associated with the
      maintenance of expression of three products that were also expressed during
      elongation at high [psi]w, the expression of a novel product, and the suppression
      of two products. In the mesocotyl, the inhibition of elongation by ABA after
      transplanting to low [psi]w was associated with the induction of a novel
      translation product. However, the induction of this product, as well as
      accumulation of ABA and inhibition of elongation, occurred without a decline in
      tissue water content. The results demonstrate the necessity of examining the
      association of gene expression with elongation responses to low [psi]w with a
      high degree of spatial resolution.

PMID- 12228617
TI  - Effect of High Temperature on Plant Growth and Carbohydrate Metabolism in Potato.
AB  - This study was undertaken to determine the role of sucrose-metabolizing enzymes
      in altered carbohydrate partitioning caused by heat stress. Potato (Solanum
      tuberosum L.) genotypes characterized as susceptible and tolerant to heat stress
      were grown at 19/17[deg]C, and a subset was transferred to 31/29[deg]C. Data were
      obtained for plant growth and photosynthesis. Enzyme activity was determined for
      sucrose-6-phosphate synthase (SPS) in mature leaves and for sucrose synthase, ADP
      glucose pyrophosphorylase, and UDP-glucose pyrophosphorylase in developing tubers
      of plants. High temperatures reduced growth of tubers more than of shoots.
      Photosynthetic rates were unaffected or increased slightly at the higher
      temperature. Heat stress increased accumulation of foliar sucrose and decreased
      starch accumulation in mature leaves but did not affect glucose. SPS activity
      increased significantly in mature leaves of plants subjected to high temperature.
      Changes in SPS activity were probably not due to altered enzyme kinetics. The
      activity of sucrose synthase and ADP-glucose pyrophosphorylase was reduced in
      tubers, albeit less quickly than leaf SPS activity. There was no interaction of
      temperature and genotype with regard to the enzymes examined; therefore, observed
      differences do not account for differences between genotypes in heat
      susceptibility.

PMID- 12228618
TI  - Studies on the Processivity of Maize DNA Polymerase 2, an [alpha]-Type Enzyme.
AB  - This paper describes studies on the processivity of an [alpha]-type DNA
      polymerase from maize (Zea mays L.) embryonic axes, designated as DNA polymerase
      2. Using poly(dA)/oligo(dT) as template, DNA polymerase 2 has a processivity of
      18 ([plus or minus]5) nucleotides incorporated, a value much lower than that
      found for wheat [alpha]-type DNA polymerase (P. Laquel, S. Litvak, M. Castroviejo
      [1993] Plant Physiol 102: 107-114). Conditions that maximally stimulate enzyme
      activity, such as 100 mM KCl and 12 mM Mg2+, are strongly inhibitory of
      processivity and cause the enzyme to become distributive under these conditions.
      Optimal concentrations for processivity are 10 mM KCl and 1 to 2 mM Mg2+. Both
      enzyme activity and processivity were found to be similar at different Mn2+
      concentrations. Both DNA polymerase 2 activity and processivity are greatly
      reduced by spermine and N-ethylmaleimide. A distinguishing feature of
      processivity in DNA polymerase 2 was the response to ATP, which not only
      stimulated processivity by more than 2-fold, but also produced a distinctive
      pattern in which the enzyme seemed to pause every 10 nucleotides, reaching a
      value of 40 to 50 nucleotides incorporated. This pattern was observed in some,
      but not all, heparin-Sepharose fractions with enzyme activity, suggesting the
      possibility of different DNA polymerase 2 complexes.

PMID- 12228619
TI  - Anion-Channel Blockers Inhibit S-Type Anion Channels and Abscisic Acid Responses
      in Guard Cells.
AB  - The effects of anion-channel blockers on light-mediated stomatal opening, on the
      potassium dependence of stomatal opening, on stomatal responses to abscisic acid
      (ABA), and on current through slow anion channels in the plasma membrane of guard
      cells were investigated. The anion-channel blockers anthracene-9-carboxylic acid
      (9-AC) and niflumic acid blocked current through slow anion channels of Vicia
      faba L. guard cells. Both 9-AC and niflumic acid reversed ABA inhibition of
      stomatal opening in V. faba L. and Commelina communis L. The anion-channel
      blocker probenecid also abolished ABA inhibition of stomatal opening in both
      species. Additional tests of 9-AC effects on stomatal aperture in Commelina
      revealed that application of this anion-channel blocker allowed wide stomatal
      opening under low (1 mM) KCI conditions and increased the rate of stomatal
      opening under both low and high (100 mM) KCI conditions. These results indicate
      that anion channels can function as a negative regulator of stomatal opening,
      presumably by allowing anion efflux and depolarization, which prohibits ion up
      take in guard cells. Furthermore, 9-AC prevented ABA induction of stomatal
      closure. A model in which ABA activation of anion channels contributes a rate
      limiting mechanism during ABA-induced stomatal closure and inhibition of stomatal
      opening is discussed.

PMID- 12228621
TI  - Inhibition of Diabrotica Larval Growth by Patatin, the Lipid Acyl Hydrolase from
      Potato Tubers.
AB  - Patatin, the nonspecific lipid acyl hydrolase from potato (Solanum tuberosum L.)
      tubers, dose-dependently inhibits the growth of southern corn rootworm (SCR) and
      western corn rootworm when fed to them on artificial diet. The 50% growth
      reduction levels are somewhat cultivar dependent, ranging from 60 to 150 [mu]g/g
      diet for neonate SCR larvae. A single patatin isoform also inhibits larval
      growth. Neonate SCR continuously exposed to patatin are halted in larval
      development. Treatment with di-isopropylfluorophosphate essentially eliminates
      patatin's phospholipase, galactolipase, and acyl hydrolase activities. SCR growth
      inhibition is eliminated also, indicating that patatin's serine hydrolase
      activity is responsible for the observed activities. Patatin-mediated
      phospholipolysis is highly pH and cultivar dependent, with specific activities up
      to 300-fold less at pH 5.5 than at pH 8.5. Esterase or phospholipase activities
      do not correlate with insect growth inhibition. Galactolipase activity, being
      cultivar and pH independent, correlates significantly with SCR growth inhibition.
      Insect-growth inhibition of patatin is significantly reduced with increased
      dietary cholesterol levels. In conclusion, patatin represents a new class of
      insect-control proteins with a novel mode of action possibly involving lipid
      metabolism.

PMID- 12228620
TI  - Chill-Induced Changes in the Activity and Abundance of the Vacuolar Proton
      Pumping Pyrophosphatase from Mung Bean Hypocotyls.
AB  - Changes in the properties of extractable vacuolar H+-pumping pyrophosphatase (V
      PPase) and vacuolar ATPase activities in chilling-sensitive seedlings of mung
      bean (Vigna radiata) were investigated. Following chilling at 4[deg]C for 48 h,
      both hydrolytic and proton-pumping activities of the V-PPase increased 1.5- to 2
      fold over controls and remained elevated even after 72 h at low temperatures.
      Vacuolar ATPase levels did not change significantly throughout the chilling
      regime. However a large increase in alcohol dehydrogenase activity during
      chilling suggests a shift toward fermentative metabolism, which can be expected
      to decrease ATPase activity in situ. Western blotting of vacuolar membrane
      enriched fractions from control and treated plants has confirmed that the changes
      in V-PPase activity are mirrored by increases in the amount of pump protein.
      Results suggest a specific role for the V-PPase in protecting chill-sensitive
      plants from the injurious effects of low temperatures via the maintenance of the
      proton gradient across the vacuolar membrane.

PMID- 12228622
TI  - Rheological Properties of Enzymatically Isolated Tomato Fruit Cuticle.
AB  - Rheological properties were determined for cuticular membranes (CMs)
      enzymatically isolated from mature tomato (Lycopersicon esculentum Mill. cv Pik
      Red) fruit. The cuticle responded as a viscoelastic polymer in stress-strain
      studies. Both CM and dewaxed CM expanded and became more elastic and susceptible
      to fracture when hydrated, suggesting that water plasticized the cuticle.
      Dewaxing of the CM caused similar changes in elasticity and fracturing,
      indicating that wax may serve as a supporting filler in the cutin matrix.
      Exposure of the cuticle to the surfactant Triton X-100 did not significantly
      affect its rheological properties.

PMID- 12228623
TI  - Cold Hardening of Spring and Winter Wheat and Rape Results in Differential
      Effects on Growth, Carbon Metabolism, and Carbohydrate Content.
AB  - The effect of long-term (months) exposure to low temperature (5[deg]C) on growth,
      photosynthesis, and carbon metabolism was studied in spring and winter cultivars
      of wheat (Triticum aestivum) and rape (Brassica napus). Cold-grown winter rape
      and winter wheat maintained higher net assimilation rates and higher in situ CO2
      exchange rates than the respective cold-grown spring cultivars. In particular,
      the relative growth rate of spring rape declined over time at low temperature,
      and this was associated with a 92% loss in in situ CO2 exchange rates. Associated
      with the high photosynthetic rates of cold-grown winter cultivars was a 2-fold
      increase per unit of protein in both stromal and cytosolic fructose-1,6
      bisphosphatase activity and a 1.5- to 2-fold increase in sucrose-phosphate
      synthase activity. Neither spring cultivar increased enzyme activity on a per
      unit of protein basis. We suggest that the recovery of photosynthetic capacity at
      low temperature and the regulation of enzymatic activity represent acclimation in
      winter cultivars. This allow these overwintering herbaceous annuals to maximize
      the production of sugars with possible cryoprotective function and to accumulate
      sufficient carbohydrate storage reserve to support basal metabolism and regrowth
      in the spring.

PMID- 12228624
TI  - Fatty Acid-Elongating Activity in Rapidly Expanding Leek Epidermis.
AB  - A microsomal fatty acid elongase activity measured in epidermis of rapidly
      expanding leek (Allium porrum L.) was 10-fold higher in specific activity than
      preparations from store-bought leek. These preparations elongated acyl chains
      effectively using endogenous or supplied primers. Elongation of C20:0 was
      specifically inhibited by 2 [mu]M cerulenin, and labeling experiments with
      [3H]cerulenin labeled two polypeptides (65 and 88 kD). ATP was required for
      maximal elongase activity in expanding leaves but was lost in nonexpanding
      tissues. Both [14C]stearoyl-coenzyme A (CoA) and [14C]stearate were maximally
      elongated in the presence of ATP. Addition of fully reduced CoA, however,
      inhibited [14C]stearate elongation, suggesting that stearoyl-CoA synthesis was
      not a prerequisite for elongation. Furthermore, microsomes preincubated with
      [14C]stearoyl-CoA plus ATP resulted in loss of radiolabel from the acyl-CoA pool
      without a corresponding loss in elongating activity. The lack of correlation
      between elongating activity and the label retained in the putative acyl-CoA
      substrate pool suggests that acyl-CoAs may not be the immediate precursors for
      elongation and that ATP plays a critical, yet undefined, role in the elongation
      process. We propose that an ATP-dependent elongating activity may generate the
      long-chain fatty acids required for wax biosynthesis.

PMID- 12228625
TI  - Tryptophan Decarboxylase, Tryptamine, and Reproduction of the Whitefly.
AB  - Tryptophan decarboxylase (TDC) from Catharanthus roseus (periwinkle) converts
      tryptophan to the indole-alkaloid tryptamine. When the TDC gene was expressed in
      transgenic tobacco, the 55-kD TDC enzyme and tryptamine accumulated. Bemisia
      tabaci (sweetpotato whitefly) reproduction on transgenic plants decreased up to
      97% relative to controls. Production of tryptamine, its derivatives, or other
      products resulting from TDC activity may discourage whitefly reproduction and
      provide a single-gene-based plant protection strategy.

PMID- 12228627
TI  - Signal Transduction in Leaf Movement.

PMID- 12228628
TI  - Ion Homeostasis in NaCl Stress Environments.

PMID- 12228629
TI  - Class I [beta]-1,3-Glucanases in the Endosperm of Tobacco during Germination.
AB  - Rupture of the seed coat and rupture of the endosperm are separate events in the
      germination of Nicotiana tabacum L. cv Havana 425 seeds. Treatment with 10-5 M
      abscisic acid (ABA) did not appreciably affect seed-coat rupture but greatly
      delayed subsequent endosperm rupture by more than 100 h and resulted in the
      formation of a novel structure consisting of the enlarging radicle with a sheath
      of greatly elongated endosperm tissue. Therefore, ABA appears to act primarily by
      delaying endosperm rupture and radicle emergence. Measurements of [beta]-1,3
      glucanase activity, antigen content, and mRNA accumulation together with reporter
      gene experiments showed that induction of class I [beta]-1,3-glucanase genes
      begins just prior to the onset of endosperm rupture but after the completion of
      seed-coat rupture. This induction was localized exclusively in the micropylar
      region of the endosperm, where the radicle will penetrate. ABA treatment markedly
      inhibited the rate of [beta]-1,3-glucanase accumulation but did not delay the
      onset of induction. Independent of the ABA concentration used, onset of endosperm
      rupture was correlated with the same [beta]-1,3-glucanase content/seed. These
      results suggest that ABA-sensitive class I [beta]-1,3-glucanases promote radicle
      penetration of the endosperm, which is a key limiting step in tobacco seed
      germination.

PMID- 12228630
TI  - Expression of the Hevea brasiliensis (H.B.K.) Mull. Arg. 3-Hydroxy-3
      Methylglutaryl-Coenzyme A Reductase 1 in Tobacco Results in Sterol
      Overproduction.
AB  - A genomic fragment encoding one (HMGR1) of the three 3-hydroxy-3-methylglutaryl
      coenzyme A reductases (HMGRs) from Hevea brasiliensis (H.B.K.) Mull. Arg. (M.-L.
      Chye, C.-T. Tan, N.-H. Chua [1992] Plant Mol Biol 19: 473-484) was introduced
      into Nicotiana tabacum L. cv xanthi via Agrobacterium transformation to study the
      influence of the hmg1 gene product on plant isoprenoid biosynthesis. Transgenic
      plants were morphologically indistinguishable from control wild-type plants and
      displayed the same developmental pattern. Transgenic lines showed an increase in
      the level of total sterols up to 6-fold, probably because of an increased
      expression level of hmg1 mRNA and a corresponding increased enzymatic activity
      for HMGR, when compared with the level of total sterols from control lines not
      expressing the hmg1 transgene. In addition to the pathway end products,
      campesterol, sitosterol, and stigmasterol, some biosynthetic intermediates such
      as cycloartenol also accumulated in transgenic tissues. Most of the overproduced
      sterols were detected as steryl-esters and were likely to be stored in
      cytoplasmic lipid bodies. These data strongly support the conclusion that plant
      HMGR is a key limiting enzyme in phytosterol biosynthesis.

PMID- 12228631
TI  - Arginine Decarboxylase Is Localized in Chloroplasts.
AB  - Plants, unlike animals, can use either ornithine decarboxylase or arginine
      decarboxylase (ADC) to produce the polyamine precursor putrescine. Lack of
      knowledge of the exact cellular and subcellular location of these enzymes has
      been one of the main obstacles to our understanding of the biological role of
      polyamines in plants. We have generated polyclonal antibodies to oat (Avena
      sativa L.) ADC to study the spatial distribution and subcellular localization of
      ADC protein in different oat tissues. By immunoblotting and immunocytochemistry,
      we show that ADC is organ specific. By cell fractionation and immunoblotting, we
      show that ADC is localized in chloroplasts associated with the thylakoid
      membrane. The results also show that increased levels of ADC protein are
      correlated with high levels of ADC activity and putrescine in osmotically
      stressed oat leaves. A model of compartmentalization for the arginine pathway and
      putrescine biosynthesis in active photosynthetic tissues has been proposed. In
      the context of endosymbiote-driven metabolic evolution in plants, the location of
      ADC in the chloroplast compartment may have major evolutionary significance,
      since it explains (a) why plants can use two alternative pathways for putrescine
      biosynthesis and (b) why animals do not possess ADC.

PMID- 12228632
TI  - The Bean Seed Storage Protein [beta]-Phaseolin Is Synthesized, Processed, and
      Accumulated in the Vacuolar Type-II Protein Bodies of Transgenic Rice Endosperm.
AB  - The seed storage protein [beta]-phaseolin of the common bean (Phaseolus vulgaris
      L.) was expressed in the endosperm of transgenic rice (Oryza sativa L.) plants.
      The 5.1- or 1.8-kb promoter fragment of the rice seed storage protein glutelin
      Gt1 gene was fused transcriptionally to either the genomic or cDNA coding
      sequence of the [beta]-phaseolin gene. The highest quantity of phaseolin
      estimated by enzyme-linked immunosorbent assay was 4.0% of the total endosperm
      protein in the transgenic rice seeds. The phaseolin trait was segregated as a
      single dominant trait with a positive gene dosage effect and was stably inherited
      through three successive generations. Both phaseolin genomic and cDNA coding
      sequences were used to synthesize four isoforms of mature phaseolin protein with
      apparent molecular masses of 51, 48, 47, and 45 kD. Enzyme deglycosylation
      experiments indicated that the 51-kD form contains high-mannose N-glycans; the 48
      and 47-kD forms have further modified N-glycans; and the 45-kD form is a
      nonglycosylated protein. Immunolabeling studies using light and electron
      microscopy demonstrated that phaseolin accumulates primarily in the vacuolar type
      II protein bodies located at the periphery of the endosperm near the aleurone
      layer. We discuss the implications of these results on nutritional improvement of
      rice grains.

PMID- 12228633
TI  - Redox Regulation of Light-Harvesting Complex II and cab mRNA Abundance in
      Dunaliella salina.
AB  - We demonstrate that photosynthetic adjustment at the level of the light
      harvesting complex associated with photosystem II (LCHII) in Dunaliella salina is
      a response to changes in the redox state of intersystem electron transport as
      estimated by photosystem II (PSII) excitation pressure. To elucidate the
      molecular basis of this phenomenon, LHCII apoprotein accumulation and cab mRNA
      abundance were examined. Growth regimes that induced low, but equivalent,
      excitation pressures (either 13[deg]C/20 [mu]mol m-2 s-1 or 30[deg]C/150 ([mu]mol
      m-2 s-1) resulted in increased LHCII apoprotein and cab mRNA accumulation
      relative to algal cultures grown under high excitation pressures (either
      13[deg]C/150 [mu]mol m-2 s-1 or 30[deg]C/2500 [mu]mol m-2 s-1). Thermodynamic
      relaxation of high excitation pressures, accomplished by shifting cultures from a
      13 to a 30[deg]C growth regime at constant irradiance for 12 h, resulted in a 6-
      and 8-fold increase in LHCII apoprotein and cab mRNA abundance, respectively.
      Similarly, photodynamic relaxation of high excitation pressure, accomplished by a
      shift from a light to a dark growth regime at constant temperature, resulted in a
      2.4- to 4-fold increase in LHCII apoprotein and cab mRNA levels, respectively. We
      conclude that photosynthetic adjustment to temperature mimics adjustment to high
      irradiance through a common redox sensing/signaling mechanism. Both temperature
      and light modulate the redox state of the first, stable quinone electron acceptor
      of PSII, which reflects the redox poise of intersystem electron transport.
      Changes in redox poise signal the nucleus to regulate cab mRNA abundance, which,
      in turn, determines the accumulation of light-harvesting apoprotein. This redox
      mechanism may represent a general acclimation mechanism for photosynthetic
      adjustment to environmental stimuli.

PMID- 12228634
TI  - How Do Stomata Read Abscisic Acid Signals?
AB  - When abscisic acid (ABA) was fed to isolated epidermis of Commelina communis L.,
      stomata showed marked sensitivity to concentrations of ABA lower than those
      commonly found in the xylem sap of well-watered plants. Stomata were also
      sensitive to the flux of hormone molecules across the epidermal strip. Stomata in
      intact leaves of Phaseolus acutifolius were much less sensitive to ABA delivered
      through the petiole than were stomata in isolated epidermis, suggesting that
      mesophyll tissue and/or xylem must substantially reduce the dose or activity of
      ABA received by guard cells. Delivery of the hormone to the leaf was varied by
      changing transpiration flux and/or concentration. Varying delivery by up to 7
      fold by changing transpiration rate had little effect on conductance. At a given
      delivery rate, variation in concentration by 1 order of magnitude significantly
      affected conductance at all but the highest concentration fed. The results are
      discussed in terms of the control of stomatal behavior in the field, where the
      delivery of ABA to the leaf will vary greatly as a function of both the
      concentration of hormone in the xylem and the transpiration rate of the plant.

PMID- 12228635
TI  - Induced Responses in Phenolic Metabolism in Two Norway Spruce Clones after
      Wounding and Inoculations with Ophiostoma polonicum, a Bark Beetle-Associated
      Fungus.
AB  - Two Norway spruce (Picea abies Karst.) clones, one resistant and the other
      susceptible to mass inoculation with Ophiostoma polonicum Siem., were compared
      with regard to their phenolic compositions and chalcone synthase (CHS) and
      stilbene synthase activities of their phloem before and at 6 and 12 d after
      artificial inoculation with sterile malt agar or O. polonicum. In unwounded
      phloem, the resistant clone differed from the susceptible clone by the presence
      of taxifolin glycoside, lower concentrations of stilbene glycosides, and higher
      CHS activity. After inoculation, (+)-catechin concentration and CHS activity
      dramatically increased around the wound, particularly in the resistant clone.
      Stilbene synthase activity also increased, but more slowly and to a lower level,
      whereas the concentrations of stilbenes remained stable. Tanning ability
      decreased in the susceptible clone, whereas it remained stable in the resistant
      one. It is proposed that the induced phenolic response of Norway spruce phloem
      consists of an activation of the phenolic pathway, finally leading to tannins and
      insoluble polymers. It is suggested that resistance to O. polonicum depends on
      the ability of the tree to easily activate the flavonoid pathway.

PMID- 12228636
TI  - Electron Partitioning between the Cytochrome and Alternative Pathways in Plant
      Mitochondria.
AB  - The contribution of the cyanide-resistant, alternative pathway to plant
      mitochondrial electron transport has been studied using a modified aqueous phase
      on-line mass spectrometry-gas chromatography system. This technique permits
      direct measurement of the partitioning of electrons between the cytochrome and
      alternative pathways in the absence of added inhibitors. We demonstrate that in
      mitochondria isolated from soybean (Glycine max L. cv Ransom) cotyledons, the
      alternative pathway contributes significantly to oxygen uptake under state 4
      conditions, when succinate is used as a substrate. However, when NADH is the
      substrate, addition of pyruvate, an allosteric activator of the alternative
      pathway, is required to achieve the same level of alternative pathway activity.
      Under state 3 conditions, when the reduction state of the ubiquinone pool is low,
      the addition of pyruvate allows the alternative pathway to compete with the
      cytochrome pathway for electrons from the ubiquinone pool when the cytochrome
      pathway is not saturated. These results provide direct experimental verification
      of the kinetics consequences of pyruvate addition on the partitioning of electron
      flow between the two respiratory pathways. This distribution of electrons between
      the two unsaturated pathways could not be measured using conventional oxygen
      electrode methods and illustrates a clear advantage of the mass spectrometry
      technique. These results have significant ramifications for studies of plant
      respiration using the oxygen electrode, particularly those studies involving
      intact tissues.

PMID- 12228637
TI  - A Specific Ascorbate Free Radical Reductase Isozyme Participates in the
      Regeneration of Ascorbate for Scavenging Toxic Oxygen Species in Potato Tuber
      Mitochondria.
AB  - Ascorbate free radical (AFR) reductase from isolated potato tuber (Solanum
      tuberosum L.) mitochondria was studied. The enzyme was purified to homogeneity
      and its physico-chemical and kinetic properties were compared to those of the
      cytosolic enzyme. The molecular mass of the mitochondrial enzyme was about 54 kD,
      whereas that of the cytosolic enzyme was about 42 kD. The Km values of
      mitochondrial AFR reductase for NADH, NADPH, and AFR were higher than those of
      the cytosolic enzyme. Moreover, the mitochondrial enzyme proved to be less
      sensitive to inhibition by sulfhydryl reagents. It was concluded that the
      ascorbate involved in the scavenging of toxic oxygen species in potato tuber
      mitochondria is regenerated via the ascorbate-glutathione pathway, in which a
      specific AFR reductase isozyme participates.

PMID- 12228638
TI  - Temperature Affects Expansion Rate of Maize Leaves without Change in Spatial
      Distribution of Cell Length (Analysis of the Coordination between Cell Division
      and Cell Expansion).
AB  - We have analyzed the way in which temperature affects leaf elongation rate of
      maize (Zea mays L.) leaves, while spatial distributions (observed at a given
      time) of cell length and of proportion of cells in DNA replication are
      unaffected. We have evaluated, in six growth chamber experiments with constant
      temperatures (from 13 to 34[deg]C) and two field experiments with fluctuating
      temperatures, (a) the spatial distributions of cell length and of leaf elongation
      rate, and (b) the distribution of cell division, either by using the continuity
      equation or by flow cytometry. Leaf elongation rate was closely related to
      meristem temperature, with a common relationship in the field and in the growth
      chamber. Cell division and cell elongation occurred in the first 20 and 60 mm
      after the ligule, respectively, at all temperatures. Similar quantitative
      responses to temperature were observed for local cell division and local tissue
      expansion rates (common x intercept and normalized slope), and both responses
      were spatially uniform over the whole expanding zone (common time courses in
      thermal time). As a consequence, faster cell elongation matched faster cell
      division rate and faster elongation was compensated for by faster cell
      displacement, resulting in temperature-invariant profiles of cell length and of
      proportion of dividing cells. Cell-to-cell communication, therefore, was not
      necessary to account for coordination.

PMID- 12228639
TI  - Ozone-Induced Ethylene Emission Accelerates the Loss of Ribulose-1,5-Bisphosphate
      Carboxylase/Oxygenase and Nuclear-Encoded mRNAs in Senescing Potato Leaves.
AB  - The relationships among O3-induced accelerated senescence, induction of ethylene,
      and changes in specific mRNA and protein levels were investigated in potato
      (Solanum tuberosum L. cv Norland) plants. When plants were exposed to 0.08 [mu]L
      L-1 O3 for 5 h d-1, steady-state levels of rbcS mRNA declined at least 5-fold in
      expanding leaves after 3 d of O3 exposure and ethylene levels increased 6- to 10
      fold. The expression of OIP-1, a 1-aminocyclopropane-1-carboxylate synthase cDNA
      from potato, correlated with increased production of ethylene and decreased
      levels of rbcS mRNA in foliage of plants treated with O3. In plants exposed to
      0.30 [mu]L L-1 O3 for 4 h, rbcS transcript levels were reduced 4-fold, whereas
      nuclear run-on experiments revealed that rbcS transcription declined an average
      of 50%. The loss of rbcS mRNA may be due, in part, to posttranscriptional
      regulation. The levels of transcripts for other chloroplast proteins,
      glyceraldehyde-3-phosphate dehydrogenase, and a photosystem II chlorophyll a/b
      binding protein decreased in O3-treated plants, in parallel with the decrease in
      rbcS mRNA. The steady-state mRNA level of a cytosolic glyceral-dehyde-3-phosphate
      dehydrogenase increased in O3-treated plants. The induction of ethylene and
      changes in transcript levels preceded visible leaf damage and decreases in
      ribulose-1,5-bisphosphate carboxylase/oxygenase protein levels.

PMID- 12228640
TI  - Electron Transport Controls Glutamine Synthetase Activity in the Facultative
      Heterotrophic Cyanobacterium Synechocystis sp. PCC 6803.
AB  - Glutamine synthetase (GS) from Synechocystis sp. PCC 6803 was inactivated in vivo
      by transferring cells from light to darkness or by incubation with the
      photosynthetic inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea but not with 2,5
      dibromo-3-methyl-6-isopropyl-p-benzoquinone. Addition of glucose prevented both
      dark and 3-(3,4-dichlorophenyl)-1,1-dimethylurea GS inactivation. In a
      Synechocystis psbE-psbF mutant (T1297) lacking photosystem II, glucose was
      required to maintain active GS, even in the light. However, in nitrogen-starved
      T1297 cells the removal of glucose did not affect GS activity. The fact that dark
      inactivated GS was reactivated in vitro by the same treatments that reactivate
      the ammonium-inactivated GS points out that both nitrogen metabolism and redox
      state of the cells lead to the same molecular regulatory mechanism in the control
      of GS activity. Using GS antibodies we detected that dark-inactivated GS
      displayed a different electrophoretic migration with respect to the active form
      in nondenaturing polyacrylamide gel electrophoresis but not in sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. The possible pathway to modulate GS
      activity by the electron transport flow in Synechocystis cells is discussed.

PMID- 12228641
TI  - Aging of Dry Desiccation-Tolerant Pollen Does Not Affect Protein Secondary
      Structure.
AB  - Protein secondary structure and membrane phase behavior in aging Typha latifolia
      pollen were studied by means of Fourier transform infrared microspectroscopy
      (FTIR). Membranes isolated from fresh pollen occurred mainly in the liquid
      crystalline phase at room temperature, whereas the membrane fluidity of aged
      pollen was drastically decreased. This decrease did not result in large-scale
      irreversible protein aggregation, as was concluded from in situ FTIR assessment
      of the amide-1 bands. Curve-fitting on the infrared absorbance spectra enabled
      estimation of the proportion of different classes of protein secondary structure.
      Membrane proteins had a relatively large amount of [alpha]-helical structure
      (48%; band at 1658 cm-1), and turn-like structures (at 1637 and 1680 cm-1) were
      also detected. The secondary protein structure of isolated cytoplasmic proteins
      resembled that of proteins in whole pollen and was conserved upon drying in the
      absence of sucrose. The isolated cytoplasmic proteins had a large amount of
      [alpha]-helical structure (43%), and also [beta]-sheet (at 1637 and 1692 cm-1)
      and turn structures were detected. Heat-denaturing experiments with intact
      hydrated pollen showed low (1627 cm-1) and high (1692 cm-1) wave number bands
      indicating irreversible protein aggregates. The results presented in this paper
      show that FTIR is an extremely suitable technique to study protein secondary
      structure in intact plant cells of different hydration levels and developmental
      stages.

PMID- 12228642
TI  - Isolation and Characterization of Biotin Carboxylase from Pea Chloroplasts.
AB  - Pea (Pisum sativum L.) leaf acetyl-coenzyme A carboxylase (ACCase) exists as two
      structurally different forms: a major, chloroplastic, dissociable form and a
      minor, multifunctional enzyme form located in the leaf epidermis. The dissociable
      form is able to carboxylate free D-biotin as an alternate substrate in place of
      the natural substrate, biotin carboxyl carrier protein. Here we report the
      purification of the biotin carboxylase component of the chloroplastic pea leaf
      ACCase. The purified enzyme, free from carboxyltransferase activity, is composed
      of two firmly bound polypeptides, one of which (38 kD) is biotinylated. In
      contrast to bacterial biotin carboxylase, which retains full activity upon
      removal of the biotin carboxyl carrier component, attempts to dissociate the two
      subunits of the plant complex led to a complete loss of biotin carboxylase
      activity. Steady-state kinetic studies of the biotin carboxylase reaction reveal
      that addition of all substrates on the enzyme is sequential and that no product
      release is possible until all three substrates (MgATP, D-biotin, bicarbonate) are
      bound to the enzyme and all chemical processes at the active site are completed.
      In agreement with this mechanism, bicarbonate-dependent ATP hydrolysis by the
      enzyme is found to be strictly dependent on the presence of exogenous D-biotin in
      the reaction medium.

PMID- 12228643
TI  - The Regulation of Carbonic Anhydrase and Ribulose-1,5-Bisphosphate
      Carboxylase/Oxygenase Activase by Light and CO2 in Chlamydomonas reinhardtii.
AB  - We have investigated the regulation of accumulation of ribulose-1,5-bisphosphate
      carboxylase/oxygenase activase and the periplasmic carbonic anhydrase (CA) in
      Chlamydomonas reinhardtii. In algae, the periplasmic CA is required for efficient
      CO2 fixation when the CO2 concentration is low. These two proteins are affected
      differently by the CO2 level in the environment. The steady-state level of the
      ribulose-1,5-bisphosphate carboxylase/oxygenase activase transcript was only
      slightly and transiently affected by a reduction in ambient CO2 concentration,
      whereas the CA transcript level was strongly induced by air containing ambient
      (350 parts per million) CO2 (low CO2) conditions. The transcripts for both
      proteins showed strong oscillations when the alga was grown under a 12-h light/12
      h dark growth regime, with the transcripts encoding these proteins present just
      before the onset of the light cycle. The observation that the CA transcript was
      made in the dark was surprising, since earlier reports indicated that active
      photosynthesis was required for the induction of the periplasmic CA. Further
      experiments demonstrated that the CA transcript was partially induced under low
      CO2 conditions even when the switch to low CO2 was done in the dark. Our results
      suggest that C. reinhardtii might sense the CO2 concentration in a more direct
      manner than through C2 or C3 cycle intermediates, which has been previously
      suggested.

PMID- 12228644
TI  - Reversible Photoinhibition in Antarctic Moss during Freezing and Thawing.
AB  - Tolerance of antarctic moss to freezing and thawing stress was investigated using
      chlorophyll a fluorescence. Freezing in darkness caused reductions in Fv/Fm
      (ratio of variable to maximum fluorescence) and Fo (initial fluorescence) that
      were reversible upon thawing. Reductions in Fv/Fm and Fo during freezing in
      darkness indicate a reduction in the potential efficiency of photosystem II that
      may be due to conformational changes in pigment-protein complexes due to
      desiccation associated with freezing. The absorption of light during freezing
      further reduced Fv/Fm and Fo but was also reversible. Using dithiothreitol (DTT),
      which inhibits the formation of the carotenoid zeaxanthin, we found reduced
      flurorescence quenching during freezing and reduced concentrations of zeaxanthin
      and antheraxanthin after freezing in DTT-treated moss. Reduced concentrations of
      zeaxanthin and antheraxanthin in DTT-treated moss were partially associated with
      reductions in nonphotochemical fluorescence quenching. The reversible
      photoinhibition observed in antarctic moss during freezing indicates the
      existence of processes that protect from photoinhibitory damage in environments
      where freezing temperatures occur in conjunction with high solar radiation
      levels. These processes may limit the need for repair cycles that require
      temperatures favorable for enzyme activity.

PMID- 12228645
TI  - Effects of Iron Limitation on Photosystem II Composition and Light Utilization in
      Dunaliella tertiolecta.
AB  - The effects of iron limitation on photosystem II (PSII) composition and
      photochemical energy conversion efficiency were studied in the unicellular
      chlorophyte alga Dunaliella tertiolecta. The quantum yield of photochemistry in
      PSII, inferred from changes in variable fluorescence normalized to the maximum
      fluorescence yield, was markedly lower in iron-limited cells and increased 3-fold
      within 20 h following the addition of iron. The decrease in the quantum yield of
      photochemistry was correlated with increased fluorescence emission from the
      antenna. In iron-limited cells, flash intensity saturation profiles of variable
      fluorescence closely followed a cumulative one-hit Poisson model, suggesting that
      PSII reaction centers are energetically isolated, whereas in iron-replete cells,
      the slope of the profile was steeper and the calculated probability of energy
      transfer between reaction centers increased to >0.6. Immunoassays revealed that
      in iron-limited cells the reaction center proteins, D1, CP43, and CP47, were
      markedly reduced relative to the peripheral light-harvesting Chl-protein complex
      of PSII, whereas the [alpha] subunit of cytochrome b559 was about 10-fold higher.
      Spectroscopic analysis established that the cytochrome b559 peptide did not
      contain an associated functional heme. We conclude that the photochemical
      conversion of absorbed excitation energy in iron-limited cells is limited by the
      number of photochemical traps per unit antenna.

PMID- 12228646
TI  - Sugar-Induced Increase of Calcium-Dependent Protein Kinases Associated with the
      Plasma Membrane in Leaf Tissues of Tobacco.
AB  - The sugar-inducible expression of genes for sporamin and [beta]-amylase in leaf
      explants of sweet potato (Ipomoea batatas) and that of a [beta]-glucuronidase
      fusion gene, with the promoter of the gene for [beta]-amylase in leaves of
      tobacco (Nicotiana tabacum), requires Ca2+ signaling (M. Ohto, K. Hayashi, M.
      Isobe, K. Nakamura [1995] Plant J 7: 297-307), and it was inhibited by
      staurosporin and K252a, inhibitors of protein kinases. Autophosphorylation
      activities of several potential protein kinases in leaves of tobacco were
      significantly higher in younger leaves than in mature leaves. However, the
      autophosphorylation activities of these proteins in mature leaves, especially
      those of the major autophosphorylatable proteins with apparent molecular masses
      of 56 and 54 kD, increased upon treatment of leaf discs with a 0.3 M solution of
      sucrose, glucose, or fructose, did not increase with sorbitol or mannitol
      treatments, and the increase by sucrose was inhibited by cycloheximide.
      Autophosphorylation of the 56- and 54-kD protein in vitro was dependent on Ca2+
      and inhibited by staurosporine, K-252a, and by W-7. These results suggest that
      they belong to the family of calcium-dependent protein kinases. They were
      concentrated in the plasma membrane fraction and were released from membrane
      vesicles by high salt or with sodium carbonate. The possible functions of these
      sugar-inducible calcium-dependent protein kinases associated with the plasma
      membrane are discussed.

PMID- 12228647
TI  - Metabolism of the Raffinose Family Oligosaccharides in Leaves of Ajuga reptans L.
      (Inter- and Intracellular Compartmentation).
AB  - We recently suggested that leaves of the frost-hardy species Ajuga reptans L.
      (Lamiaceace) contain two pools of raffinose family oligosaccharides (RFO): a
      large long-term storage pool in the mesophyll, possibly also involved in frost
      resistance, and a transport pool in the phloem (M. Bachmann, P. Matile, F. Keller
      [1994] Plant Physiol 105: 1335-1345). In the present study, the inter- and
      intracellular compartmentation of anabolic RFO metabolism was investigated by
      comparing whole-leaf tissue with mesophyll protoplasts and vacuoles. The studies
      showed the mesophyll to be the primary site of RFO synthesis in A. reptans.
      Mesophyll protoplasts were capable of RFO formation upon in vitro 14CO2
      photosynthesis. Sucrose-phosphate synthase, galactinol synthase, and the
      galactinol-independent galactosyltransferase, which is responsible for RFO chain
      elongation, were located predominantly in the mesophyll protoplasts. The
      percentage of stachyose synthase in the mesophyll changed greatly during the cold
      acclimation period (from 26% at the beginning to 88% after 20 d). The remainder
      was most probably in the intermediary cells of the phloem. Compartmentation
      studies in which mesophyll protoplasts were compared with vacuoles isolated from
      them showed that, of the components of the RFO storage pool, galactinol synthase,
      stachyose synthase, myo-inositol, galactinol, and sucrose were extravacuolar
      (most probably cytosolic), whereas galactinol-independent galactosyltransferase
      and higher RFO oligomers (with degree of polymerization 4) were vacuolar.
      Raffinose was found in both locations and might serve as a cryoprotectant.

PMID- 12228648
TI  - Fractionation and Structural Characterization of Arabinogalactan-Proteins from
      the Cell Wall of Rose Cells.
AB  - Arabinogalactan-proteins (AGPs) have been purified from Paul's Scarlet rose (Rosa
      sp.) cell walls. As estimated by gel permeation chromatography, the apparent
      molecular masses of the two major cell-wall AGP fractions were 130 and 242 kD.
      Since the 130-kD AGP had a ratio of arabinose/glucuronic acid that was 12 times
      higher than that of the 242-kD AGP, the fractions were named cell-wall AGP1 (CW
      AGP1) and glucuronogalactan-protein (GGP), respectively. CW-AGP1 and GGP
      contained predominantly t-arabinofuranosyl residues; 3-linked, 6-linked, and 3,6
      branched galactopyranosyl residues; and 4-linked and t-glucuronopyranosyl
      residues. The 1H-nuclear magnetic resonance spectra of CW-AGP1 and GGP showed
      that the arabinofuranosyl and galactopyranosyl residues were predominantly in
      [alpha]- and [beta]-anomeric configuration, respectively, and that GGP contained
      a few O-acetyl residues. The protein moieties of CW-AGP1 and GGP were both rich
      in hydroxyproline and alanine but differed in the percentage of various amino
      acids, including hydroxyproline, alanine, serine, and glycine. Cell-wall AGPs
      bound to ([beta]-D-glucosyl)3 Yariv phenylglycoside, but the stoichiometry of
      binding was about 6 times greater in GGP than in other Rosa AGPs. GGP seems to be
      peculiar to the cell wall, since no similar molecule was found in the culture
      medium.

PMID- 12228649
TI  - A Negative Hydraulic Message from Oxygen-Deficient Roots of Tomato Plants?
      (Influence of Soil Flooding on Leaf Water Potential, Leaf Expansion, and
      Synchrony between Stomatal Conductance and Root Hydraulic Conductivity).
AB  - Four to 10 h of soil flooding delayed and suppressed the normal daily increase in
      root hydraulic conductance (Lp) in tomato (Lycopersicon esculentum Mill. cv Ailsa
      Craig) plants. The resulting short-term loss of synchrony between Lp and stomatal
      conductance decreased leaf water potential ([psi]L) relative to well-drained
      plants within 2 h. A decrease in [psi]L persisted for 8 h and was mirrored by
      decreased leaf thickness measured using linear displacement transducers. After 10
      h of flooding, further closing of stomata and re-convergence of Lp in flooded and
      well-drained roots returned [psi]L to control values. In the second photoperiod,
      Lp in flooded plants exceeded that in well-drained plants in association with
      much increased Lp and decreased stomatal conductance. Pneumatic balancing
      pressure applied to roots of intact flooded plants to prevent temporary loss of
      [psi]L in the 1st d did not modify the patterns of stomatal closure or leaf
      expansion. Thus, the magnitude of the early negative hydraulic message was
      neither sufficient nor necessary to promote stomatal closure and inhibit leaf
      growth in flooded tomato plants. Chemical messages are presumed to be responsible
      for these early responses to soil flooding.

PMID- 12228650
TI  - Involvement of Free Calcium in Action of Cryptogein, a Proteinaceous Elicitor of
      Hypersensitive Reaction in Tobacco Cells.
AB  - Treatment of suspension-cultured tobacco (Nicotiana tabacum var Xanthi) cells
      with cryptogein, a proteinaceous elicitor from Phytophthora cryptogea, induced a
      great stimulation of Ca2+ influx within the first minutes. Ca2+ influx is
      essential for the initiation of cryptogein-induced responses, since
      ethyleneglycol-bis([beta]-amino-ethyl ether)-N,N[prime]-tetraacetic acid or La3+,
      which block Ca2+ entrance, suppress cryptogein-induced responses such as
      extracellular alkalinization, active oxygen species, and phytoalexin production.
      Moreover, once initiated, these responses require sustained Ca2+ influx within
      the 1st h. A Ca2+ ionophore (A23187) was able to trigger an extracellular
      alkalinization but not the formation of active oxygen species and phytoalexins,
      even in the presence of cryptogein. Staurosporine, a protein kinase inhibitor
      that was recently reported to suppress cryptogein-induced responses (M.-P. Viard,
      F. Martin, A. Pugin, P. Ricci, J.-P. Blein [1994] Plant Physiol 104: 1245-1249),
      inhibited Ca2+ influx induced by cryptogein in a dose-dependent manner. These
      results suggest that protein phosphorylation followed by Ca2+ influx might be
      involved in the initial steps of cryptogein signal transduction.

PMID- 12228651
TI  - Quantitative Aspects of the in Vivo Regulation of Pyrophosphate:Fructose-6
      Phosphate 1-Phosphotransferase by Fructose-2,6-Bisphosphate.
AB  - Pyrophosphate:fructose-6-phosphate 1-phosphotransferase (PFP) was quantified in
      developing barley (Hordeum vulgare) leaves by immunostaining on western blots
      using a purified preparation of barley leaf PFP as standard. Fructose-2,6
      bisphosphate (Fru-2,6-bisP) was quantified in the same tissues. Depending on age
      and tissue development, the concentration of PFP varied between 11 and 80 [mu]g
      PFP protein g-1 fresh weight, which corresponds to 0.09 to 0.65 nmol g-1 fresh
      weight of each of the [alpha] and [beta] PFP subunits. The level depends
      primarily on the maturity of the tissue. In the same tissues the concentration of
      Fru-2,6-bisP varied between 0.07 and 0.46 nmol g-1 fresh weight. Thus, the
      concentrations of PFP subunits and Fru-2,6-bisP were of the same order of
      magnitude. In young leaf tissues the concentration of PFP subunits may exceed the
      concentration of Fru-2,6-bisP. This means that the amount of Fru-2,6-bisP present
      will be too low to occupy all the allosteric binding sites on PFP even though the
      concentration of Fru-2,6-bisP exceeds the Ka(Fru-2,6-bisP) by several orders of
      magnitude. These results are discussed in relation to Fru-2,6-bisP as a regulator
      of enzyme activities under in vivo conditions.

PMID- 12228652
TI  - Decreased Photosystem II Core Phosphorylation in a Yellow-Green Mutant of Wheat
      Showing Monophasic Fluorescence Induction Curve.
AB  - In the present work we study the regulation of the distribution of the
      phosphorylated photosystem II (PSII) core populations present in grana regions of
      the thylakoids from several plant species. The heterogeneous nature of PSII core
      phosphorylation has previously been reported (M.T. Giardi, F. Rigoni, R. Barbato
      [1992] Plant Physiol 100: 1948-1954; M.T. Giardi [1993] Planta 190: 107-113). The
      pattern of four phosphorylated PSII core populations in the grana regions appears
      to be ubiquitous in higher plants. In the dark, at least two phosphorylated PSII
      core populations are always detected. A mutant of wheat (Triticum durum) that
      shows monophasic room-temperature photoreduction of the primary quinone electron
      acceptor of PSII as measured by chlorophyll fluorescence increase in the presence
      and absence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea and by fluorescence upon
      flash illumination in intact leaves also lacks the usual distribution of
      phosphorylated PSII core populations. In this mutant, the whole PSII core
      population pattern is changed, probably due to altered threonine kinase activity,
      which leads to the absence of light-induced phosphorylation of CP43 and D2
      proteins. The results, correlated to previous experiments in vivo, support the
      idea that the functional heterogeneity observed by fluorescence is correlated in
      part to the PSII protein phosphorylation in the grana.

PMID- 12228653
TI  - Amylolytic Activities in Cereal Seeds under Aerobic and Anaerobic Conditions.
AB  - An adequate carbohydrate supply contributes to the survival of seeds under
      conditions of limited oxygen availability. The amount of soluble, readily
      fermentable carbohydrates in dry cereal seeds is usually very limited, with
      starch representing the main storage compound. Starch breakdown during the
      germination of cereal seeds is the result of the action of hydrolytic enzymes and
      only through the concerted action of [alpha]-amylase (EC 3.2.1.1), [beta]-amylase
      (EC 3.2.1.2), debranching enzyme (EC 3.2.1.41), and [alpha]-glucosidase (EC
      3.2.1.20) can starch be hydrolyzed completely. We present here data concerning
      the complete set of starch-degrading enzymes in three cereals, rice (Oryza sativa
      L.), which is tolerant to anaerobiosis, and wheat (Triticum aestivum L.) and
      barley (Hordeum vulgare L.), which are unable to germinate under anoxia. Among
      the cereal seeds tested under anoxia, only rice is able to degrade nonboiled,
      soluble starch, reflecting the ability to degrade the starch granules in vivo.
      This is explained by the presence of the complete set of enzymes needed to
      degrade starch completely either as the result of de novo synthesis ([alpha]
      amylase, [beta]-amylase) or activation of preexisting, inactive forms of the
      enzyme (debranching enzyme, [alpha]-glucosidase). These enzymes are either absent
      or inactive in wheat and barley seeds kept under anaerobic conditions.

PMID- 12228654
TI  - Actin Filaments in Mature Guard Cells Are Radially Distributed and Involved in
      Stomatal Movement.
AB  - Stomatal movements, which regulate gas exchange in plants, involve pronounced
      changes in the shape and volume of the guard cell. To test whether the changes
      are regulated by actin filaments, we visualized microfilaments in mature guard
      cells and examined the effects of actin antagonists on stomatal movements.
      Immunolocalization on fixed cells and microinjection of fluorescein
      isothiocyanate-phalloidin into living guard cells of Commelina communis L. showed
      that cortical microfilaments were radially distributed, fanning out from the
      stomatal pore site, resembling the known pattern of microtubules. Treatment of
      epidermal peels with phalloidin prior to stabilizing microfilaments with m
      maleimidobenzoyl N-hydroxysuccimimide caused dense packing of radial
      microfilaments and an accumulation of actin around many organelles. Both stomatal
      closing induced by abscisic acid and opening under light were inhibited.
      Treatment of guard cells with cytochalasin D abolished the radial pattern of
      microfilaments; generated sparse, poorly oriented arrays; and caused partial
      opening of dark-closed stomata. These results suggest that microfilaments
      participate in stomatal aperture regulation.

PMID- 12228655
TI  - Enzymes of Choline Synthesis in Spinach (Response of Phospho-Base N
      Methyltransferase Activities to Light and Salinity).
AB  - In spinach (Spinacia oleracea L.), choline is synthesized by the sequential N
      methylation of phosphoethanolamine -> phosphomono- -> phosphodi- ->
      phosphotrimethylethanolamine (i.e. phosphocholine) followed by hydrolysis to
      release choline. Differential centrifugation of spinach leaf extracts shows that
      enzymes catalyzing the three N-methylations are cytosolic. These enzymes were
      assayed in leaf extracts prepared from plants growing under various light/dark
      periods. Under a diurnal, 8-h light/16-h dark photoperiod, the activity of the
      enzyme catalyzing the N-methylation of phosphoethanolamine is highest at the end
      of the light period and lowest following the dark period. Prolonged dark periods
      (exceeding 16 h) lead to a further reduction in the activity of this enzyme,
      although activity is restored when plants are reexposed to light. In contrast,
      the activity of the enzyme(s) catalyzing the N-methylations of phosphomono- and
      phosphodimethylethanolamine does not undergo comparable changes in response to
      light/dark treatments. Salt shock of plants with 200 mM NaCl results in a 2-fold
      increase in all three N-methylation activities relative to nonsalinized controls
      but only in plants exposed to light. Thus, light is required for the salt
      responsive up-regulation of choline synthesis in spinach.

PMID- 12228656
TI  - Local and Systemic Biosynthesis of Salicylic Acid in Infected Cucumber Plants.
AB  - Radiolabeling studies showed that salicylic acid (SA), an essential component in
      the signal transduction pathway leading to systemic acquired resistance, is
      synthesized from phenylalanine (Phe) and benzoic acid in cucumber (Cucumis
      sativus L.) plants inoculated with pathogens. Leaf discs from plants inoculated
      with either tobacco necrosis virus or Pseudomonas lachrymans incorporated more
      [14C]Phe into [14C]SA than mock-inoculated controls. The identity of SA was
      confirmed by gas chromatography-mass spectrometry. No reduction in specific
      activity of [14C]SA was observed for either free or bound SA between control and
      infected plants after feeding [14C]Phe. A specific inhibitor of Phe ammonia
      lyase, 2-aminoindan-2-phosphonic acid, completely inhibited the incorporation of
      [14C]Phe into [14C]SA, although plants treated with 2-aminoindan-2-phosphonic
      acid could still produce [14C]SA from [14C]benzoic acid. Biosynthesis of SA in
      tissue inoculated with tobacco necrosis virus followed a transient pattern with
      the highest induction occurring 72 h postinoculation. Uninfected tissues from an
      infected plant synthesized de novo more SA than did controls. This suggests the
      involvement of a systemic signal triggering SA synthesis in tissue distant from
      the site of infection that display systemic acquired resistance.

PMID- 12228657
TI  - Purification and Partial Characterization of Tomato Extensin Peroxidase.
AB  - Early plant defense response is characterized by elevation of activity of
      peroxidases and enhanced insolubilization of hydroxyproline-rich glycoproteins,
      such as extensin, in the cell wall. The insolubilization process (cross-linking
      between soluble extensin precursor molecules) is catalyzed by extensin
      peroxidases. We have ionically eluted extensin peroxidases from intact water
      washed suspension-cultured tomato (hybrid of Lycopersicon esculentum Mill. and
      Lycopersicon peruvianum L. [Mill.]) cells and purified them to homogeneity by
      molecular sieve and cation-exchange chromatography. Four ionic forms of
      peroxidase (PI,PII,EPIII, and EPIV) were resolved; only the latter two cross
      linked tomato soluble extensin. The molecular weight (34,000-37,000), amino acid
      composition, and isoelectric point (9.0) of the extensin peroxidases were
      determined. Substrate specificities of the enzymes were investigated: soluble
      extensin and potato lectin (a hydroxyproline-rich glycoprotein with a domain that
      strongly resembles extensin) were cross-linked by only two forms of the enzyme,
      whereas bovine serum albumin, aldolase, insulin, a number of other marker
      proteins, and proteins eluted from tomato cells (except extensin) could not be
      cross-linked. We have also isolated a yeast elicitor that enhances total
      peroxidase activity and extensin insolubilization within 1 h of challenge in
      cultured cells of tomato. A highly sensitive enzyme-linked immunosorbent assay
      technique using polyclonal antiserum raised against soluble tomato extensin was
      used to demonstrate extensin insolubilization in vivo. A tomato cell-wall
      peroxidase that cross-links extensin has been purified and may have a role in
      plant defense.

PMID- 12228658
TI  - Publish and Perish? The Rules of the Game.

PMID- 12228659
TI  - Cell Ablation Reveals That Expression from the Phaseolin Promoter Is Confined to
      Embryogenesis and Microsporogenesis.
AB  - Most previous studies of the [beta]-phaseolin (phas) gene, which encodes the
      major storage protein in bean (Phaseolus vulgaris L.), have shown its expression
      to be rigorously confined to the developing seed, both in bean and transgenic
      tobacco (Nicotiana tabacum L. cv Xanthi) plants. To confirm unequivocally the
      lack of phas expression in vegetative tissues, we placed the diphtheria toxin A
      chain (DT-A) coding region under the control of [beta]-phaseolin promoter
      sequences. Tobacco plants transgenic for phas/DT-A were phenotypically normal
      until flowering, when they produced anthers that were externally normal but
      contained no viable pollen. Microscopic examination of immature anthers revealed
      a normal tapetum, but the pollen mother cells did not undergo meiosis and
      subsequently degenerated, resulting in male-sterile plants. This demonstration of
      phas expression during microsporogenesis was corroborated by the expression of
      [beta]-glucuronidase in pollen of plants transformed with comparable phas/uidA
      constructs. Although these findings suggested that similarities in phas
      expression may exist between seed and pollen maturation, no phas activity could
      be detected in bean pollen. After fertilization of the DT-A-transformed plants
      with pollen from wild-type tobacco, 50% of the resulting embryos aborted at the
      heart stage, defining this as the earliest time for phas expression during
      embryogenesis.

PMID- 12228660
TI  - Sugar-Binding Activity of Pea Lectin Expressed in White Clover Hairy Roots.
AB  - Introduction of the pea (Pisum sativum L.) lectin (PSL) gene into white clover
      (Trifolium repens L.) hairy roots facilitates nodulation by the nitrogen-fixing
      bacterium Rhizobium leguminosarum biovar viciae, which normally nodulates pea and
      not white clover (C.L. Diaz, L.S. Melchers, P.J.J. Hooykaas, B.J.J. Lugtenberg,
      and J.W. Kijne [1989] Nature 338: 579-581). Here, we show that PSL is
      functionally expressed in transgenic white clover hairy roots transformed with
      the PSL gene. PSL could be isolated from these roots by affinity chromatography.
      Immunoanalysis of PSL showed the presence of polypeptides corresponding to the
      PSL precursor and its [beta] subunits. In addition, we developed a highly
      sensitive localization technique based on specific binding of a glycan moiety of
      rat IgE to PSL. Similar to the situation in pea roots, PSL appeared to be
      localized on the external cell surface of elongated epidermal cells and on the
      tips of emerging and growing root hairs of transgenic white clover hairy roots.
      PSL was not observed on normal white clover roots and on hairy roots without the
      PSL gene. These results show that (a) in transgenic white clover hairy roots, PSL
      is correctly processed and targeted to root cells susceptible to rhizobial
      infection, and (b) like in pea roots, PSL is surface bound with at least one of
      its two sugar-binding sites available for (rhizobial) ligands.

PMID- 12228661
TI  - Altered Growth and Wood Characteristics in Transgenic Hybrid Aspen Expressing
      Agrobacterium tumefaciens T-DNA Indoleacetic Acid-Biosynthetic Genes.
AB  - A key regulator of cambial growth is the plant hormone indoleacetic acid (IAA).
      Here we report on altered wood characteristics and growth patterns in transgenic
      hybrid aspen (Populus tremula L. x Populus tremuloides Michx.) expressing
      Agrobacterium tumefaciens T-DNA IAA-biosynthetic iaaM and iaaH genes. Eighteen
      lines simultaneously expressing both genes were regenerated. Of these, four
      lines, verified to be transgenic by northern blot analysis, were selected and
      raised under controlled growth conditions. All four lines were affected in their
      growth patterns, including alterations in height and stem diameter growth,
      internode elongation, leaf enlargement, and degree of apical dominance. Two
      transgenic lines, showing the most distinct phenotypic deviation from the wild
      type, were characterized in more detail for free and conjugated IAA levels and
      for wood characteristics. Both lines showed an altered IAA balance, particularly
      in mature leaves and roots where IAA levels were elevated. They also exhibited
      changes in wood anatomy, most notably a reduction in vessel size, an increase in
      vessel density, and changes in ray development. Thus, the recent development of
      techniques for gene transfer to forest trees enabled us to investigate the
      influence of an altered IAA balance on xylem development in an intact
      experimental system. In addition, the results demonstrate the possibility of
      manipulating wood properties in a forest tree through controlled changes of IAA
      concentration and distribution.

PMID- 12228662
TI  - The Function of Ascorbic Acid in Photosynthetic Phosphorylation.
AB  - Ascorbate is oxidized to the free radical monodehydroascorbate by O2.- and by
      H2O2 (through the action of ascorbate peroxidase) formed in the Mehler reaction
      by isolated spinach (Spinacia oleracea) thylakoids. Light-dependent electron
      transport from water to monodehydroascorbate is shown to be coupled to ATP
      formation with a ratio ATP:O2 of 2. In the presence of ascorbate the net O2
      exchange balance of the Mehler reaction is close to zero, and the synthesis of
      ATP is increased 2 to 3 times due to the extra electron transport to the
      monodehydroascorbate free radical. A scheme of the electron transport in the
      presence of ascorbate is discussed.

PMID- 12228663
TI  - The Role of Ethylene in Interorgan Signaling during Flower Senescence.
AB  - The roles of 1-aminocyclopropane-1-carboxylic acid (ACC) and ethylene in
      interorgan signaling during senescence in orchid (Cymbidium) flowers were
      investigated. Following application of radiolabeled ACC to the stigma or the
      rostellum (modified lobe of the stigma), radiolabeled ethylene is produced by all
      flower parts. In intact flowers as well as in excised central columns, stigma- or
      rostellum-applied ACC or [alpha]-aminoisobutyric acid were largely immobile.
      Local treatment of the central column of previously aminoethoxyvinylglycine
      treated flowers with either ethylene or 2-chloroethylphosphonic acid (ethephon)
      rapidly induced emission of ethylene from the petals, showing that ethylene is
      readily translocated within the flower. Creation of alternative outlets
      (incisions) in the labellum or the central column significantly delayed the
      occurrence of senescence symptoms in ACC-treated flowers. The results do not
      confirm the presumed role of ACC as a signal in interorgan communication during
      flower senescence. In these flowers, ethylene produced in the stigmatic region
      following pollination or emasculation serves as a mobile factor responsible for
      senescence symptoms observed in other flower parts.

PMID- 12228664
TI  - Purification and Characterization of a Novel (R)-Mandelonitrile Lyase from the
      Fern Phlebodium aureum.
AB  - Using high-performance liquid chromatography and nuclear magnetic resonance we
      identified vicianin as the cyanogenic compound of Phlebodium aureum. The (R)
      hydroxynitrile lyase involved during cyanogenesis in the catabolism of the
      aglycon ([R]-mandelonitrile) was purified to apparent homogeneity. The purified
      holoenzyme is a homomultimer with subunits of Mr = 20,000. At least three
      isoforms of the enzyme exist. In contrast to other hydroxynitrile lyases,
      mandelonitrile lyase (MDL) from P. aureum was not inhibited by sulfhydryl- or
      hydroxyl-modifying reagents, suggesting a different catalytic mechanism. The
      enzyme is active over a broad temperature range, with maximum activity between 35
      and 50[deg]C, and a pH optimum at 6.5. In contrast to (R)-MDLs isolated from
      several species of the Rosaceae family, (R)-MDL from P. aureum is not a
      flavoprotein. The substrate specificity was investigated using immobilized enzyme
      and diisopropyl ether as solvent. The addition of cyanide to aromatic and
      heterocyclic carbonyls is catalyzed by this (R)-MDL, whereas aliphatic carbonyls
      are poorly converted.

PMID- 12228665
TI  - Purification and Properties of ent-Kaurene Synthase B from Immature Seeds of
      Pumpkin.
AB  - ent-Kaurene synthase B (KSB) was purified 291-fold from a crude enzyme
      preparation from endosperm of pumpkin (Cucurbita maxima L.). Separation of ent
      kaurene synthase A and KSB was achieved by hydrophobic interaction
      chromatography. The fractions containing KSB activity were further purified by
      diethylaminoethyl, phenyl, and hydroxyapatite column chromatography. Using sodium
      dodecyl phosphate-polyacrylamide gel electrophoresis, the purest enzyme
      preparation showed a major band at an apparent molecular mass of 81 kD. The
      amount of protein in this band was correlated with KSB activity after
      diethylaminoethyl and hydroxyapatite chromatography. The N terminus of the 81-kD
      protein was blocked. Therefore, the protein was partially digested with protease
      and the amino acid sequences of the resulting major peptide fragments were
      analyzed. A polyclonal antibody was raised against a synthetic peptide based on
      the longest peptide fragment combined with a keyhole limpet hemocyanin. The
      antibody recognized only the 81-kD denatured protein and not the native KSB. The
      properties of KSB were examined using the phenyl-purified enzyme preparation. The
      Km value for copalyl pyrophosphate was 0.35 [mu]M, and the optimal pH was 6.8 to
      7.5. The KSB activity required divalent cations such as Mg2+, Mn2+, and Co2+,
      whereas Cu2+, Ca2+, and Ba2+ inhibited the activity.

PMID- 12228666
TI  - Changes in Isozyme Profiles of Catalase, Peroxidase, and Glutathione Reductase
      during Acclimation to Chilling in Mesocotyls of Maize Seedlings.
AB  - The response of antioxidants to acclimation and chilling in various tissues of
      dark-grown maize (Zea mays L.) seedlings was examined in relation to chilling
      tolerance and protection from chilling-induced oxidative stress. Chilling caused
      an accumulation of H2O2 in both the coleoptile + leaf and the mesocotyl (but not
      roots), and acclimation prevented this accumulation. None of the antioxidant
      enzymes were significantly affected by acclimation or chilling in the coleoptile
      + leaf or root. However, elevated levels of glutathione in acclimated seedlings
      may contribute to an enhanced ability to scavenge H2O2 in the coleoptile + leaf.
      In the mesocotyl (visibly most susceptible to chilling), catalase3 was elevated
      in acclimated seedlings and may represent the first line of defense from
      mitochondria-generated H2O2. Nine of the most prominent peroxidase isozymes were
      induced by acclimation, two of which were located in the cell wall, suggesting a
      role in lignification. Lignin content was elevated in mesocotyls of acclimated
      seedlings, likely improving the mechanical strength of the mesocotyl. One
      cytosolic glutathione reductase isozyme was greatly decreased in acclimated
      seedlings, whereas two others were elevated, possibly resulting in improved
      effectiveness of the enzyme at low temperature. When taken together, these
      responses to acclimation illustrate the potential ways in which chilling
      tolerance may be improved in preemergent maize seedlings.

PMID- 12228667
TI  - Evidence for a Mechanically Induced Oxidative Burst.
AB  - Rapid release of H2O2 may constitute an initial defense response mounted by a
      plant. Inauguration of this oxidative burst is known to occur upon stimulation
      with chemical elicitors, but the possibility of mechanical elicitation arising
      from pathogen penetration/weakening of the cell wall has never been examined. To
      introduce an adjustable mechanical stress on the plasma membrane, cultured
      soybean (Glycine max Merr. cv Kent) cells were subjected to defined changes in
      medium osmolarity. Dilution of the medium with water or resuspension of cells in
      sucrose solutions of reduced osmolarity yielded an oxidative burst similar to
      those stimulated by chemical elicitors. Furthermore, the magnitude of oxidant
      biosynthesis and osmotic stress correlated directly. Upon return of the cells to
      normal tonicity, the oxidative burst abruptly halted, indicating that its
      expression depended on maintenance of the osmotic stress and not on any external
      chemical signal. To confirm the ability of soybean cells to respond to a
      mechanical stimulus with induction of an oxidative burst, cells were subjected to
      direct physical pressure. Application of pressure yielded a characteristic
      oxidative burst. Because neither these cells nor those subjected to osmotic
      pressure were damaged by their treatments, we conclude that plant cells can
      detect mechanical disturbances and initiate a classical defense reaction in
      response.

PMID- 12228668
TI  - Plasma Membrane H+-ATPase in Maize Roots Induced for NO3- Uptake.
AB  - Plasma membrane H+-ATPase was studied in maize (Zea mays L.) roots induced for
      NO3- uptake. Membrane vesicles were isolated by means of Suc density gradient
      from roots exposed for 24 h either to 1.5 mM NO3- or 1.5 mM SO4-. The two
      populations of vesicles had similar composition as shown by diagnostic inhibitors
      of membrane-associated ATPases. However, both ATP-dependent intravesicular H+
      accumulation and ATP hydrolysis were considerably enhanced (60-100%) in vesicles
      isolated from NO3--induced roots. Km for Mg:ATP and pH dependency were not
      influenced by NO3- treatment of the roots. ATP hydrolysis in plasma membrane
      vesicles for both control and NO3--induced roots was not affected by 10 to 150 mM
      NO3- or Cl-. On the other hand, kinetics of NO3-- or Cl--stimulated ATP-dependent
      intravesicular H+ accumulation were modified in plasma membrane vesicles isolated
      from NO3-- induced roots. Immunoassays carried out with polyclonal antibodies
      against plasma membrane H+-ATPase revealed an increased steady-state level of the
      enzyme in plasma membrane vesicles isolated from NO3--induced roots. Results are
      consistent with the idea of an involvement of plasma membrane H+-ATPase in the
      overall response of roots to NO3-.

PMID- 12228669
TI  - Sucrose Synthase Localization during Initiation of Seed Development and Trichome
      Differentiation in Cotton Ovules.
AB  - Sucrose synthase in cotton (Gossypium hirsutum L.) ovules was immunolocalized to
      clarify the relationship between this enzyme and (a) sucrose import/utilization
      during initiation of seed development, (b) trichome differentiation, and (c) cell
      wall biosynthesis in these rapidly elongating "fibers." Analyses focused on the
      period immediately before and after trichome initiation (at pollination).
      Internal tissues most heavily immunolabeled were the developing nucellus,
      adjacent integument (inner surface), and the vascular region. Little sucrose
      synthase was associated with the outermost epidermis on the day preceding
      pollination. However, 1 d later, immunolabel appeared specifically in those
      epidermal cells at the earliest visible phase of trichome differentiation. The
      day following pollination, these cells had elongated 3- to 5-fold and showed a
      further enhancement of sucrose synthase immunolabel. Levels of sucrose synthase
      mRNA also increased during this period, regardless of whether pollination per se
      had occurred. Timing of onset for the cell-specific localization of sucrose
      synthase in young seeds and trichome initials indicates a close association
      between this enzyme and sucrose import at a cellular level, as well as a
      potentially integral role in cell-wall biosynthesis.

PMID- 12228670
TI  - Inorganic Carbon-Stimulated O2 Photoreduction Is Suppressed by NO2- Assimilation
      in Air-Grown Cells of Synechococcus UTEX 625.
AB  - The effect of NO2- assimilation on O2 exchange and CO2 fixation of the
      cyanobacterium, Synechococcus UTEX 625, was studied mass spectrometrically. Upon
      addition of 1 mM inorganic carbon to the medium, inorganic carbon pools developed
      and accelerated O2 photoreduction 5-fold when CO2 fixation was inhibited. During
      steady-state photosynthesis at saturating light, O2 uptake represented 32% of O2
      evolution and balanced that portion of O2 evolution that could not be accounted
      for by CO2 fixation. Under these conditions, NO2- assimilation reduced O2 uptake
      by 59% but had no influence on CO2 fixation. NO2- assimilation decreased both CO2
      fixation and O2 photoreduction at low light and and increased net O2 evolution at
      all light intensities. The increase in net O2 evolution observed during
      simultaneous assimilation of carbon and nitrogen over carbon alone was due to a
      suppression of O2 photoreduction by NO2- assimilation. When CO2 fixation was
      precluded, NO2- assimilation inhibited O2 photoreduction and stimulated O2
      evolution. When the electron supply was limiting (low light), competition among
      O2, CO2, and NO2- for electrons could be observed, but when the electron supply
      was not limiting (saturating light), O2 photoreduction and/or NO2- reduction
      caused electron transport that was additive to that for maximum CO2 fixation.

PMID- 12228671
TI  - Decarboxylation of Malate in the Crassulacean Acid Metabolism Plant Bryophyllum
      (Kalanchoe) fedtschenkoi (Role of NAD-Malic Enzyme).
AB  - The role of NAD-malic enzyme (NAD-ME) in the Crassulacean acid metabolism plant
      Bryophyllum (Kalanchoe) fedtschenkoi was investigated using preparations of
      intact and solubilized mitochondria from fully expanded leaves. Intact, coupled
      mitochondria isolated during the day or night did not differ in their ability to
      take up [14C]malic acid from the surrounding medium or to respire using malate or
      succinate as substrate. However, intact mitochondria isolated from plants during
      the day decarboxylated added malate to pyruvate significantly faster than
      mitochondria isolated from plants at night. NAD-ME activity in solubilized
      mitochondrial extracts showed hysteretic kinetics and was stimulated by a number
      of activators, including acetyl-coenzyme A, fructose-1,6-bisphosphate, and
      sulfate ions. In the absence of these effectors, reaction progress curves were
      nonlinear, with a pronounced acceleration phase. The lag period before a steady
      state rate was reached in assays of mitochondrial extracts decreased during the
      photoperiod and increased slowly during the period of darkness. However, these
      changes in the kinetic properties of the enzyme could not account for the changes
      in the rate of decarboxylation of malate by intact mitochondria. Gel-filtration
      experiments showed that mitochondrial extracts contained three forms of NAD-ME
      with different molecular weights. The relative proportions of the three forms
      varied somewhat throughout the light/dark cycle, but this did not account for the
      changes in the kinetics behavior of the enzyme during the diurnal cycle.

PMID- 12228672
TI  - Electrochemical Potential Gradients of H+, K+, Ca2+, and Cl- across the Tonoplast
      of the Green Alga Eremosphaera Viridis.
AB  - Using ion-selective microelectrodes, we measured the activity of H+, K+, Ca2+,
      and Cl- and the electrical potential both in the vacuole and in the cytoplasm of
      the unicellular green alga Eremosphaera viridis to obtain comparable values of
      the named parameters from the same object under identical conditions. The cytosol
      had a pH of 7.3, and activities of the other ions were 130 mM K+, 160 nM Ca2+,
      and 2.2 mM Cl-. We observed only small and transient light-dependent changes of
      the cytosolic Ca2+ activity. The vacuolar K+ activity did not differ
      significantly from the cytosolic one. The Ca2+ activity inside the vacuole was
      approximately 200 [mu]M, the pH was 5.0, and the Cl- activity was 6.2 mM. The
      concentrations of K+, Ca2+, and Cl- in cell extracts were measured by induction
      coupled plasma spectroscopy and anion chromatography. This confirmed the vacuolar
      activities for K+ and Cl- obtained with ion-selective microelectrodes and
      indicated that approximately 60% of the vacuolar Ca2+ was buffered. The tonoplast
      potential was vanishingly low ([less than or equal to][plus or minus]2 mV). There
      was no detectable electrochemical potential gradient for K+ across the tonoplast,
      but there was, however, an obvious electrochemical potential gradient for Cl- (
      26 mV), indicating an active accumulation of Cl- inside the vacuole.

PMID- 12228674
TI  - Factors Affecting Development of Peroxisomes and Glycolate Metabolism among Algae
      of Different Evolutionary Lines of the Prasinophyceae.
AB  - Leaf-type peroxisomes are not present in the primitive unicellular Prasinophycean
      line of algae but are present in the multicellular algae Mougeotia, Chara, and
      Nitella, which are in the one evolutionary line, Charophyceae, that led to higher
      plants. Processes related to glycolate metabolism that may have been modified or
      induced with the appearance of peroxisomes have been examined. The algal
      dissolved inorganic carbon-concentrating mechanism and alkalization of the medium
      during photosynthesis were not lost when peroxisomes appeared in the members of
      the Charophycean line of algae. Therefore, it is unlikely that lowering of the
      CO2 concentration in the environment was a major factor in the evolutionary
      appearance of peroxisomes. Multicellular Mougeotia, early members of the
      Charophycean line of algae, have peroxisomes, but they excrete excess glycolate
      into the medium. The cytosolic pyruvate reductase for D-lactate synthesis and the
      glycolate dehydrogenase activity almost disappeared when peroxisomal glycolate
      oxidase, which also oxidizes L-lactate, appeared. These biochemical changes do
      not indicate what caused the induction of leaf-type peroxisomes in this
      evolutionary line of algae. The oxygenase activity of ribulose-1,5-bisphosphate
      carboxylase/oxygenase and glycolate oxidase require about 200 to 400 [mu]M O2 for
      0.5 Vmax. These high-O2-requiring steps in glycolate metabolism would have
      functioned faster with increasing atmospheric O2, which might have been the
      causative factor in the induction of peroxisomes.

PMID- 12228673
TI  - Is the Reaction Catalyzed by 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase a
      Rate-Limiting Step for Isoprenoid Biosynthesis in Plants?
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) catalyzes the irreversible
      conversion of 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate and is
      considered a key regulatory step controlling isoprenoid metabolism in mammals and
      fungi. The rate-limiting nature of this enzyme for isoprenoid biosynthesis in
      plants remains controversial. To investigate whether HMGR activity could be
      limiting in plants, we introduced a constitutively expressing hamster HMGR gene
      into tabacco (Nicotiana tabaccum L.) plants to obtain unregulated HMGR activity.
      The impact of the resulting enzyme activity on the biosynthesis and accumulation
      of particular isoprenoids was evaluated. Expression of the hamster HMGR gene led
      to a 3- to 6-fold increase in the total HMGR enzyme activity. Total sterol
      accumulation was consequently increased 3- to 10-fold, whereas end-product
      sterols such as sitosterol, campesterol, and stigmasterol were increased only 2
      fold. The level of cycloartenol, a sterol biosynthetic intermediate, was
      increased more than 100-fold. Although the synthesis of total sterols appears to
      be limited normally by HMGR activity, these results indicate that the activity of
      one or more later enzyme(s) in the pathway must also be involved in determining
      the relative accumulation of end-product sterols. The levels of other isoprenoids
      such as carotenoids, phytol chain of chlorophyll, and sesquiterpene phytoalexins
      were relatively unaltered in the transgenic plants. It appears from these results
      that compartmentation, channeling, or other rate-determining enzymes operate to
      control the accumulation of these other isoprenoid end products.

PMID- 12228675
TI  - Plasma Membrane Sterols Are Essential for Sensing Osmotic Changes in the
      Halotolerant Alga Dunaliella.
AB  - The halotolerant alga Dunaliella responds to hyperosmotic stress by synthesis of
      massive amounts of glycerol. The trigger for this osmotic response is the change
      in cell volume, but the mechanism that senses volume changes is not known.
      Preincubation of Dunaliella salina with tridemorph, a specific inhibitor of
      sterol biosynthesis, inhibits glycerol synthesis and volume recovery. The
      inhibition is associated with suppression of [14C]bicarbonate incorporation into
      sterols and is correlated with pronounced depletion of plasma membrane sterols.
      Incubation of sterol-depleted cells with cholesterol hemisuccinate restores the
      capacity for volume regulation in response to hyperosmotic stress. Tridemorph as
      well as lovastatin also inhibit volume changes that are induced by high light in
      Dunaliella bardawil, a species that responds to high light intensity by synthesis
      of large amounts of [beta]-carotene. These volume changes result from
      accumulation of glycerol and are associated with de novo synthesis of sterols.
      The major plasma membrane sterol in D. salina and the high-light-induced sterol
      in D. bardawil co-migrate with ergosterol on thin-layer chromatography and on
      reversed-phase high-performance liquid chromatography. These results suggest that
      the osmosensory mechanism in Dunaliella resides in the plasma membrane, and that
      sterols have an important role in sensing osmotic changes.

PMID- 12228676
TI  - In Situ Glutamine Synthetase Activity in a Marine Unicellular Alga (Development
      of a Sensitive Colorimetric Assay and the Effects of Nitrogen Status on Enzyme
      Activity).
AB  - A malachite green colorimetric assay for glutamine synthetase is described.
      Glutamine synthetase activity was determined in situ in the marine diatom
      Phaeodactylum tricornutum Bohlin using cells permeabilized by freeze/thawing.
      Higher activities were obtained with cells permeabilized in N-2
      hydroxyethylpiperazine-N[prime]-2-ethanesulfonic acid compared with N
      tris(hydroxymethyl)methyl-3-aminopropanesulfonic acid,
      tris(hydroxymethyl)aminomethane, or imidazole, and the optimum pH was 7.9.
      Activities were higher in cells permeabilized in the presence of reductant,
      particularly dithiothreitol. Glutamine synthetase activities were markedly
      decreased in the presence of methionine sulfoximine. In the presence of
      saturating concentrations of glutamate and ATP, the apparent Km for ammonia was
      320 [mu]M, but this value decreased to 110 [mu]M with subsaturating
      concentrations of glutamate and ATP. The apparent Km values for glutamate and
      ATP, in the presence of saturating concentrations of ammonia, were 9.7 and 2.9
      mM, respectively. Ammonia-grown cells had lower glutamine synthetase activities
      than did nitrate-grown cells. During nitrogen starvation of both ammonia- and
      nitrate-grown cells, glutamine synthetase activities increased rapidly during the
      first 8 h, reaching maximum values after 24 to 48 h. Moreover, the time course
      for the increases in glutamine synthetase activities and rate of methylamine
      uptake following the transfer of nitrate-grown cells to nitrogen-deficient medium
      were very similar. In nitrate-grown cells and cells deprived of combined
      nitrogen, glutamine synthetase activities and maximum rates of ammonia uptake
      gave comparable values when measured at the same temperature (20[deg]C).

PMID- 12228677
TI  - Temperature and Abscisic Acid Can Be Used to Regulate Survival, Growth, and
      Differentiation of Cultured Guard Cell Protoplasts of Tree Tobacco.
AB  - Guard cell protoplasts isolated from leaves of Nicotiana glauca (Graham) were
      cultured. Conditions were sought that would maximize survival and maintain cells
      in their differentiated state. Temperature was an important determinant of
      survival, growth, and differentiation. As temperatures were increased from 24 to
      32[deg]C, survival for 1 week in culture increased from approximately 20% to
      approximately 80% of cells used to initiate cultures. At all of these
      temperatures, approximately 90% of surviving cells divided to form callus tissue.
      "Footprint" areas of cells cultured for 1 week at 32[deg]C increased almost 30
      fold. Cells cultured for 1 week at 34 to 40[deg]C also survived in high
      percentages (approximately 80%), but they retained a morphology similar to that
      of guard cells and they did not divide. Footprint areas of cells cultured for 1
      week at 38[deg]C increased 6-fold. Cells cultured at 36 to 40[deg]C in media
      containing 0.1 or 1.0 [mu]M abscisic acid survived in high percentages and did
      not divide. At 38[deg]C their footprint areas did not increase, but cells so
      cultured increased in diameter when treated with fusicoccin. Morphologies and
      electrophoretic profiles of total sodium dodecyl sulfate-extractable proteins
      suggest that cells cultured at 38[deg]C in media containing abscisic acid remain
      differentiated. L-[alpha]-(2-Aminoethoxyvinyl)-glycine reduced survival to <1% at
      26 or 32[deg]C but had no effect at 38[deg]C. At lower temperatures, cell growth
      and survival appear to be ethylene dependent.

PMID- 12228678
TI  - Oxidation of Imported or Endogenous Carbohydrates by Isolated Chloroplasts from
      Green Pepper Fruits.
AB  - Recently, we demonstrated that intact chloroplasts isolated from green pepper
      (Capsicum annum L.) fruits use exogenous glucose-6-phosphate (Glc-6-P) as the
      most efficient precursor for starch biosynthesis (O. Batz, R. Scheibe, H.E.
      Neuhaus [1995] Planta 196: 50-57). Here we demonstrate that these chloroplasts
      transport this hexose phosphate in counter-exchange for orthophosphate. By
      measuring the release of 14CO2 from [1-14C]Glc-6-P, we show that isolated fruit
      chloroplasts also use exogenous Glc-6-P as a substrate for the oxidative pentose
      phosphate pathway. The rate of decarboxylation appears to be linear with time and
      is significantly reduced in the presence of Triton X-100, indicating that the
      reaction is dependent on plastid integrity. Pyruvate has been identified as a
      positive effector for flux through the oxidative pentose-phosphate pathway.
      However, the highest rates of Glc-6-P-driven oxidative pentosephosphate pathway
      activity are achieved in the presence of nitrite, 2-oxoglutarate, and glutamine,
      indicating a strong interaction between nitrogen metabolism and this pathway. In
      addition, we show that carbohydrates liberated during starch mobilization are
      used as substrates for the oxidative pentose-phosphate pathway. Orthophosphate
      was found to act as an activator for the observed 14CO2 release from
      carbohydrates formerly bound as starch. In this context, we demonstrate that
      exogenous Glc-6-P competes with endogenous carbohydrates. A possible interaction
      between exogenous and endogenous carbohydrates is discussed with respect to
      altered levels of carbohydrates during fruit development.

PMID- 12228679
TI  - Mechanisms of Cadmium Mobility and Accumulation in Indian Mustard.
AB  - Indian mustard (Brassica juncea L.), a high biomass crop plant, accumulated
      substantial amounts of cadmium, with bioaccumulation coefficients (concentration
      of Cd in dry plant tissue/concentration in solution) of up to 1100 in shoots and
      6700 in roots at nonphytotoxic concentrations of Cd (0.1 [mu]g/mL) in solution.
      This was associated with a rapid accumulation of phytochelatins in the root,
      where the majority of the Cd was coordinated with sulfur ligands, probably as a
      Cd-S4 complex, as demonstrated by x-ray absorption spectroscopy. In contrast, Cd
      moving in the xylem sap was coordinated predominantly with oxygen or nitrogen
      ligands. Cd concentrations in the xylem sap and the rate of Cd accumulation in
      the leaves displayed similar saturation kinetics, suggesting that the process of
      Cd transport from solution through the root and into the xylem is mediated by a
      saturable transport system(s). However, Cd translocation to the shoot appeared to
      be driven by transpiration, since ABA dramatically reduced Cd accumulation in
      leaves. Within leaves, Cd was preferentially accumulated in trichomes on the leaf
      surface, and this may be a possible detoxification mechanism.

PMID- 12228680
TI  - Increased 1-Aminocyclopropane-1-Carboxylic Acid Oxidase Activity in Shoots of
      Flooded Tomato Plants Raises Ethylene Production to Physiologically Active
      Levels.
AB  - Soil flooding increased 1-aminocyclopropane-1-carboxylic (ACC) acid oxidase
      activity in petioles of wild-type tomato (Lycopersicon esculentum L.) plants
      within 6 to 12 h in association with faster rates of ethylene production.
      Petioles of flooded plants transformed with an antisense construct to one isoform
      of an ACC oxidase gene (ACO1) produced less ethylene and had lower ACC oxidase
      activity than those of the wild type. Flooding promoted epinastic curvature but
      did so less strongly in plants transformed with the antisense construct than in
      the wild type. Exogenous ethylene, supplied to well-drained plants, also promoted
      epinastic curvature, but transformed and wild-type plants responded similarly.
      Flooding increased the specific delivery (flux) of ACC to the shoots (picomoles
      per second per square meter of leaf) in xylem sap flowing from the roots. The
      amounts were similar in both transformed and wild-type plants. These observations
      demonstrate that changes in ACC oxidase activity in shoot tissue resulting from
      either soil flooding or introducing ACC oxidase antisense constructs can
      influence rates of ethylene production to a physiologically significant extent.
      They also implicate systemic root to shoot signals in regulating the activity of
      ACC oxidase in the shoot.

PMID- 12228681
TI  - Subsaturating Ribulose-1,5-Bisphosphate Concentration Promotes Inactivation of
      Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase (Rubisco) (Studies Using
      Continuous Substrate Addition in the Presence and Absence of Rubisco Activase).
AB  - We developed a continuous-addition method for maintaining subsaturating
      concentrations of ribulose-1,5-bisphosphate (RuBP) for several minutes, while
      simultaneously monitoring its consumption by ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco). This method enabled us to observe the effects of
      subsaturating RuBP and CO2 concentrations on the activity of Rubisco during much
      longer periods than previously studied. At saturating CO2, the activity of the
      enzyme declined faster when RuBP was maintained at concentrations near its Km
      value than when RuBP was saturating. At saturating RuBP, activity declined faster
      at limiting than at saturating CO2, in accordance with previous observations. The
      most rapid decline in activity occurred when both CO2 and RuBP concentrations
      were subsaturating. The activity loss was accompanied by decarbamylation of the
      enzyme, even though the enzyme was maintained at the same CO2 concentration
      before and after exposure to RuBP. Rubisco activase ameliorated the decline in
      activity at subsaturating CO2 and RuBP concentrations. The results are consistent
      with a proposed mechanism for regulating the carbamylation of Rubisco, which
      postulates that Rubisco activase counteracts Rubisco's unfavorable carbamylation
      equilibrium in the presence of RuBP by accelerating, in an ATP-dependent manner,
      the release of RuBP from its complex with uncarbamylated sites.

PMID- 12228682
TI  - Apoplastic pH and Ammonium Concentration in Leaves of Brassica napus L.
AB  - A vacuum infiltration technique was developed that enabled the extraction of
      apoplastic solution with very little cytoplasmic contamination as evident from a
      malate dehydrogenase activity of less than 1% in the apoplastic solution relative
      to that in bulk leaf extracts. The volume of apoplastic water, a prerequisite for
      determination of the concentration of apoplastic solutes, was determined by
      vacuum infiltration of indigo carmine with subsequent analysis of the dilution of
      the dye in apoplastic extracts. Indigo carmine was neither transported across the
      cell membrane nor significantly adsorbed to the cell walls, ensuring reproducible
      (SE < 2%) and precise determination of apoplastic water. Analysis of leaves from
      four different positions on senescing Brassica napus plants showed a similar
      apoplastic pH of 5.8, while apoplastic NH4+ increased from 1.1 mM in lower leaves
      to 1.3 mM in upper leaves. Inhibition of glutamine synthetase in young B. napus
      plants resulted in increasing apoplastic pH from 6.0 to 6.8 and increasing
      apoplastic NH4+ concentration from 1.0 to 25.6 mM, followed by a marked increase
      in NH3 emission. Calculating NH3 compensation points for B. napus plants on the
      basis of measured apoplastic H+ and NH4+ concentrations gave values ranging from
      4.3 to 5.9 nmol NH3 mol-1 air, consistent with an estimate of 5.3 [plus or minus]
      3.6 nmol NH3 mol-1 air obtained by NH3 exchange experiments in growth chambers. A
      strong linear relationship was found between calculated NH3 compensation points
      and measured NH3 emission rates in glutamine synthetase-inhibited plants.

PMID- 12228683
TI  - Suborganellar Localization and Molecular Characterization of Nonproteolytic
      Degraded Leukoplast Pyruvate Kinase from Developing Castor Oil Seeds.
AB  - Plastid pyruvate kinase (PKp) activity and anti-(castor oil seed [COS] PKp)
      immunoglobulin G immunoreactive polypeptides were recovered in the stroma but not
      from envelope membranes of purified COS leukoplasts that had been subfractionated
      by sucrose density gradient centrifugation. The PKp was highly purified from
      isolated leukoplasts using anion-exchange and ADP-agarose chromatographies.
      Proteolysis of PKp was almost entirely eliminated by including 2,2[prime]
      dipyridyl disulfide in purification buffers. The final preparation contained 63.5
      kD ([alpha] subunit) and 54-kD ([beta] subunit) polypeptides that stained for
      protein and cross-reacted with anti-(COS PKp) immunoglobulin G with similar
      intensities. These two polypeptides co-eluted following gel-filtration
      chromatography and co-migrated during nondenaturing isoelectric focusing
      polyacrylamide gel electrophoresis. The enzyme's native Mr was estimated to be
      334,000. This PKp thus appears to exist as an [alpha]3[beta]3-heterohexamer.
      Comparison of the respective N-terminal sequences of the [alpha] and [beta]
      subunits with the deduced amino acid sequences for several PKp cDNAs indicated
      that (a) the [alpha] and [beta] subunits are encoded by COS genes previously
      designated as PKpA and PKpG, respectively, and (b) respective transit peptides of
      4.8- and 5.5-kD are cleaved from the [alpha] and [beta] subunit preproteins
      following their translocation into the leukoplast.

PMID- 12228684
TI  - A Calorimetric Study of the Glass Transition Behaviors in Axes of Bean Seeds with
      Relevance to Storage Stability.
AB  - Although the presence of intracellular aqueous glasses has been established in
      seeds, their physiological role in storage stability is still conjectural.
      Therefore, we examined, using differential scanning calorimetry, the thermal
      behavior of glass transitions in axes of bean (Phaseolus vulgaris L.) with water
      contents (WC) between 0 and 1 g H2O/g dry weight (g/g) and temperatures between 
      120 and +120[deg]C. Three types of thermal behaviors associated with the glass
      transition were observed. The appearance, the glass -> liquid transition
      temperature, and the amount of energy released during these transitions were
      dependent on the tissue WC. No glass transitions were observed at WC lower than
      0.03 and higher than 0.45 g/g. A brief exposure to 100[deg]C altered the glass
      properties of tissues with WC between 0.03 and 0.08 g/g but did not affect the
      thermal behavior of glasses with higher WC, demonstrating that thermal history is
      important to the intracellular glass behavior at lower WC. Correspondence of data
      from bean to models predicting the effects of glass components on the glass ->
      liquid transition temperature suggests that the intracellular glasses are
      composed of a highly complex sugar matrix, in which sugar and water molecules
      interact together and influence the glass properties. Our data provide evidence
      that additional glass properties must be characterized to understand the
      implications of a glassy state in storage stability of seeds.

PMID- 12228685
TI  - Morphometric Analysis of Rice Seed Protein Bodies (Implication for a Significant
      Contribution of Prolamine to the Total Protein Content of Rice Endosperm).
AB  - Electron microscopic observation of thin sections of rice (Oryza sativa L.)
      endosperm revealed two types of protein bodies (PBs): spherical and irregular
      shaped ones. Immunocytochemical localization studies using antibodies raised
      against purified glutelins, prolamines, and globulins indicated that the
      prolamines were localized in the spherical PB, whereas the irregular-shaped PB
      contained glutelins and globulins. We counted and measured the surface area and
      the relative volume of 2303 PBs randomly selected from two different
      developmental stages and from different locations within the endosperm. The ratio
      of spherical to irregular-shaped PBs was 1:1.6. Double-label immunogold electron
      microscopic localization indicated that the globulins represented about 18% of
      the surface area of the irregular-shaped PBs. Based on our morphometric analysis,
      we estimate the relative contribution of glutelin as 53%, that of prolamine as
      35%, and that of globulin as 12% of the total seed protein.

PMID- 12228687
TI  - Why is a liberal education so elusive?

PMID- 12228686
TI  - Humped pattern of diversity: fact or artifact?

PMID- 12228688
TI  - British science. Pioneering stem cell bank will soon be open for deposits.

PMID- 12228689
TI  - European science. Framework and stem cells: The fight goes on.

PMID- 12228691
TI  - Impact hazard. A little respect for the asteroid threat.

PMID- 12228690
TI  - Sustainable development. World summit adopts voluntary action plan.

PMID- 12228692
TI  - Biodiversity. Bid to save Kamchatka's wildlife.

PMID- 12228693
TI  - Nutrition research. IOM panel weighs in on diet and health.

PMID- 12228694
TI  - Undergraduate science. Biology departments urged to bone up.

PMID- 12228695
TI  - Informatics. The genome chose its alphabet with care.

PMID- 12228696
TI  - Patent laws. Report urges leeway for developing world.

PMID- 12228697
TI  - Cell biology. Ubiquitin lives up to its name.

PMID- 12228698
TI  - American Chemical Society meeting. Chemists search for solutions.

PMID- 12228699
TI  - Transgenic species. Engineered fish: friend or foe of the environment?

PMID- 12228700
TI  - Environmental radioactivity. Radioecology's coming of age--or its last gasp?

PMID- 12228701
TI  - Environmental radioactivity. New findings allay concerns over depleted uranium.

PMID- 12228702
TI  - Public health vs. civil liberties.

PMID- 12228703
TI  - Climate change. North-south connections.

PMID- 12228704
TI  - Geology. Genesis of the world's largest gold deposits.

PMID- 12228705
TI  - Membrane fusion. Caught in the act.

PMID- 12228706
TI  - Biochemistry. Sense and sensitivity--controlling the ribosome.

PMID- 12228707
TI  - Quantum optics. Quantum logic with light, glass, and mirrors.

PMID- 12228708
TI  - Cancer. BRCA2 enters the fray.

PMID- 12228709
TI  - Molecular biology. Chromatin higher order folding--wrapping up transcription.
AB  - Eukaryotic genomes are organized into condensed, heterogeneous chromatin fibers
      throughout much of the cell cycle. Here we describe recent studies indicating
      that even transcriptionally active loci may be encompassed within 80- to 100
      nanometer-thick chromonema fibers. These studies suggest that chromatin higher
      order folding may be a key feature of eukaryotic transcriptional control. We also
      discuss evidence suggesting that adenosine-5'-triphosphate-dependent chromatin
      remodeling enzymes and histone-modifying enzymes may regulate transcription by
      controlling the extent and dynamics of chromatin higher order folding.

PMID- 12228710
TI  - BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA
      structure.
AB  - Mutations in the BRCA2 (breast cancer susceptibility gene 2) tumor suppressor
      lead to chromosomal instability due to defects in the repair of double-strand DNA
      breaks (DSBs) by homologous recombination, but BRCA2's role in this process has
      been unclear. Here, we present the 3.1 angstrom crystal structure of a
      approximately 90-kilodalton BRCA2 domain bound to DSS1, which reveals three
      oligonucleotide-binding (OB) folds and a helix-turn-helix (HTH) motif. We also
      (i) demonstrate that this BRCA2 domain binds single-stranded DNA, (ii) present
      its 3.5 angstrom structure bound to oligo(dT)9, (iii) provide data that implicate
      the HTH motif in dsDNA binding, and (iv) show that BRCA2 stimulates RAD51
      mediated recombination in vitro. These findings establish that BRCA2 functions
      directly in homologous recombination and provide a structural and biochemical
      basis for understanding the loss of recombination-mediated DSB repair in BRCA2
      associated cancers.

PMID- 12228711
TI  - A proton buffering role for silica in diatoms.
AB  - For 40 million years, diatoms have dominated the reverse weathering of silica on
      Earth. These photosynthetic protists take up dissolved silicic acid from the
      water and precipitate opaline silica to form their cell wall. We show that the
      biosilica of diatoms is an effective pH buffer, enabling the enzymatic conversion
      of bicarbonate to CO2, an important step in inorganic carbon acquisition by these
      organisms. Because diatoms are responsible for one-quarter of global primary
      production and for a large fraction of the carbon exported to the deep sea, the
      global cycles of Si and C may be linked mechanistically.

PMID- 12228712
TI  - Water diffusion and clustering on Pd(111).
AB  - The adsorption, diffusion, and clustering of water molecules on a Pd(111) surface
      were studied by scanning tunneling microscopy. At 40 kelvin, low-coverage water
      adsorbs in the form of isolated molecules, which diffuse by hopping to nearest
      neighbor sites. Upon collision, they form first dimers, then trimers, tetramers,
      and so on. The mobility of these species increased by several orders of magnitude
      when dimers, trimers, and tetramers formed, and decreased again when the cluster
      contained five or more molecules. Cyclic hexamers were found to be particularly
      stable. They grow with further exposure to form a commensurate hexagonal
      honeycomb structure relative to the Pd(111) substrate. These observations
      illustrate the change in relative strength between intermolecular hydrogen bonds
      and molecule-substrate bonds as a function of water cluster size, the key
      property that determines the wetting properties of materials.

PMID- 12228713
TI  - A major Archean, gold- and crust-forming event in the Kaapvaal craton, South
      Africa.
AB  - The 2.89- to 2.76-gigayear-old conglomerates of the Central Rand Group of South
      Africa host an immense concentration of gold. The gold and rounded pyrites from
      the conglomerates yield a rhenium-osmium isochron age of 3.03 +/- 0.02 gigayears
      and an initial 187Os/188Os ratio of 0.1079 +/- 0.0001. This age is older than
      that of the conglomerates. Thus, the gold is detrital and was not deposited by
      later hydrothermal fluids. This Middle Archean gold mineralization event
      corresponds to a period of rapid crustal growth in which much of the Kaapvaal
      craton was formed and is evidence for a significant noble metal flux from the
      mantle.

PMID- 12228714
TI  - Deformation on nearby faults induced by the 1999 Hector Mine earthquake.
AB  - Interferometric Synthetic Aperture Radar observations of surface deformation due
      to the 1999 Hector Mine earthquake reveal motion on several nearby faults of the
      eastern California shear zone. We document both vertical and horizontal
      displacements of several millimeters to several centimeters across kilometer-wide
      zones centered on pre-existing faults. Portions of some faults experienced
      retrograde (that is, opposite to their long-term geologic slip) motion during or
      shortly after the earthquake. The observed deformation likely represents elastic
      response of compliant fault zones to the permanent co-seismic stress changes. The
      induced fault displacements imply decreases in the effective shear modulus within
      the kilometer-wide fault zones, indicating that the latter are mechanically
      distinct from the ambient crustal rocks.

PMID- 12228715
TI  - Relative timing of deglacial climate events in Antarctica and Greenland.
AB  - The last deglaciation was marked by large, hemispheric, millennial-scale climate
      variations: the Bolling-Allerod and Younger Dryas periods in the north, and the
      Antarctic Cold Reversal in the south. A chronology from the high-accumulation Law
      Dome East Antarctic ice core constrains the relative timing of these two events
      and provides strong evidence that the cooling at the start of the Antarctic Cold
      Reversal did not follow the abrupt warming during the northern Bolling transition
      around 14,500 years ago. This result suggests that southern changes are not a
      direct response to abrupt changes in North Atlantic thermohaline circulation, as
      is assumed in the conventional picture of a hemispheric temperature seesaw.

PMID- 12228716
TI  - Instruction of translating ribosome by nascent peptide.
AB  - Expression of the tryptophanase operon of Escherichia coli is regulated by
      catabolite repression and tryptophan-induced transcription antitermination. An
      induction site activated by l-tryptophan is created in the translating ribosome
      during synthesis of TnaC, the 24-residue leader peptide. Replacing the tnaC stop
      codon with a tryptophan codon allows tryptophan-charged tryptophan transfer RNA
      to substitute for tryptophan as inducer. This suggests that the ribosomal A site
      occupied by the tryptophanyl moiety of the charged transfer RNA is the site of
      induction. The location of tryptophan-12 of nascent TnaC in the peptide exit
      tunnel was crucial for induction. These results show that a nascent peptide
      sequence can influence translation continuation and termination within a
      translating ribosome.

PMID- 12228717
TI  - Potential regulatory function of human dendritic cells expressing indoleamine 2,3
      dioxygenase.
AB  - Antigen-presenting cells (APCs) can induce tolerance or immunity. We describe a
      subset of human APCs that express indoleamine 2,3-dioxygenase (IDO) and inhibit T
      cell proliferation in vitro. IDO-positive APCs constituted a discrete subset
      identified by coexpression of the cell-surface markers CD123 and CCR6. In the
      dendritic cell (DC) lineage, IDO-mediated suppressor activity was present in
      fully mature as well as immature CD123+ DCs. IDO+ DCs could also be readily
      detected in vivo, which suggests that these cells may represent a regulatory
      subset of APCs in humans.

PMID- 12228718
TI  - A photoactivatable GFP for selective photolabeling of proteins and cells.
AB  - We report a photoactivatable variant of the Aequorea victoria green fluorescent
      protein (GFP) that, after intense irradiation with 413-nanometer light, increases
      fluorescence 100 times when excited by 488-nanometer light and remains stable for
      days under aerobic conditions. These characteristics offer a new tool for
      exploring intracellular protein dynamics by tracking photoactivated molecules
      that are the only visible GFPs in the cell. Here, we use the photoactivatable GFP
      both as a free protein to measure protein diffusion across the nuclear envelope
      and as a chimera with a lysosomal membrane protein to demonstrate rapid
      interlysosomal membrane exchange.

PMID- 12228719
TI  - Observation of a membrane fusion intermediate structure.
AB  - We report the observation of a phase of phospholipid that contains a structure
      similar to the commonly postulated interbilayer state that is crucial to membrane
      fusion. The widely accepted model for membrane fusion suggests that there is an
      intermediate state in which the two contacting monolayers become continuous via
      an hourglass-shaped structure called a stalk. Many efforts have been made to
      estimate the free energy for such a state in order to understand the
      functionality of membrane fusion proteins and to define key parameters in energy
      estimates. The observation of the stalk structure supports the stalk hypothesis
      for membrane fusion and enables the measurement of these parameters
      experimentally.

PMID- 12228720
TI  - "Stemness": transcriptional profiling of embryonic and adult stem cells.
AB  - The transcriptional profiles of mouse embryonic, neural, and hematopoietic stem
      cells were compared to define a genetic program for stem cells. A total of 216
      genes are enriched in all three types of stem cells, and several of these genes
      are clustered in the genome. When compared to differentiated cell types, stem
      cells express a significantly higher number of genes (represented by expressed
      sequence tags) whose functions are unknown. Embryonic and neural stem cells have
      many similarities at the transcriptional level. These results provide a
      foundation for a more detailed understanding of stem cell biology.

PMID- 12228721
TI  - A stem cell molecular signature.
AB  - Mechanisms regulating self-renewal and cell fate decisions in mammalian stem
      cells are poorly understood. We determined global gene expression profiles for
      mouse and human hematopoietic stem cells and other stages of the hematopoietic
      hierarchy. Murine and human hematopoietic stem cells share a number of expressed
      gene products, which define key conserved regulatory pathways in this
      developmental system. Moreover, in the mouse, a portion of the genetic program of
      hematopoietic stem cells is shared with embryonic and neural stem cells. This
      overlapping set of gene products represents a molecular signature of stem cells.

PMID- 12228722
TI  - Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense
      transcripts.
AB  - The mechanism by which disruption of reading frame can influence pre-messenger
      RNA (pre-mRNA) processing is poorly understood. We assessed the role of factors
      essential for nonsense-mediated mRNA decay (NMD) in nonsense-mediated altered
      splicing (NAS) with the use of RNA interference (RNAi) in mammalian cells.
      Inhibition of rent1/hUpf1 expression abrogated both NMD and NAS of nonsense T
      cell receptor beta transcripts. In contrast, inhibition of rent2/hUpf2 expression
      did not disrupt NAS despite achieving comparable stabilization of nonsense
      transcripts. We also demonstrate that NAS and NMD are genetically separable
      functions of rent1/hUpf1. Additionally, rent1/hUpf1 enters the nucleus where it
      may directly influence early events in mRNA biogenesis. This provides compelling
      evidence that NAS relies on a component of the nonsense surveillance machinery
      but is not an indirect consequence of NMD.

PMID- 12228724
TI  - ENSO and cholera: a nonstationary link related to climate change?
AB  - We present here quantitative evidence for an increased role of interannual
      climate variability on the temporal dynamics of an infectious disease. The
      evidence is based on time-series analyses of the relationship between El
      Nino/Southern Oscillation (ENSO) and cholera prevalence in Bangladesh (formerly
      Bengal) during two different time periods. A strong and consistent signature of
      ENSO is apparent in the last two decades (1980-2001), while it is weaker and
      eventually uncorrelated during the first parts of the last century (1893-1920 and
      1920-1940, respectively). Concomitant with these changes, the Southern
      Oscillation Index (SOI) undergoes shifts in its frequency spectrum. These changes
      include an intensification of the approximately 4-yr cycle during the recent
      interval as a response to the well documented Pacific basin regime shift of 1976.
      This change in remote ENSO modulation alone can only partially serve to
      substantiate the differences observed in cholera. Regional or basin-wide changes
      possibly linked to global warming must be invoked that seem to facilitate ENSO
      transmission. For the recent cholera series and during specific time intervals
      corresponding to local maxima in ENSO, this climate phenomenon accounts for over
      70% of disease variance. This strong association is discontinuous in time and can
      only be captured with a technique designed to isolate transient couplings.

PMID- 12228725
TI  - Bacteriophage T4 RNA ligase 2 (gp24.1) exemplifies a family of RNA ligases found
      in all phylogenetic domains.
AB  - RNA ligases participate in repair, splicing, and editing pathways that either
      reseal broken RNAs or alter their primary structure. Bacteriophage T4 RNA ligase
      (gp63) is the best-studied member of this class of enzymes, which includes yeast
      tRNA ligase and trypanosome RNA-editing ligases. Here, we identified another RNA
      ligase from the bacterial domain--a second RNA ligase (Rnl2) encoded by phage T4.
      Purified Rnl2 (gp24.1) catalyzes intramolecular and intermolecular RNA strand
      joining through ligase-adenylate and RNA-adenylate intermediates. Mutational
      analysis identifies amino acids required for the ligase-adenylation or
      phosphodiester synthesis steps of the ligation reaction. The catalytic residues
      of Rnl2 are located within nucleotidyl transferase motifs I, IV, and V that are
      conserved in DNA ligases and RNA capping enzymes. Rnl2 has scant amino acid
      similarity to T4 gp63. Rather, Rnl2 exemplifies a distinct ligase family, defined
      by variant motifs, that includes the trypanosome-editing ligases and a group of
      putative RNA ligases encoded by eukaryotic viruses (baculoviruses and an
      entomopoxvirus) and many species of archaea. These findings have implications for
      the evolution of covalent nucleotidyl transferases and virus-host dynamics based
      on RNA restriction and repair.

PMID- 12228727
TI  - Olfactory search at high Reynolds number.
AB  - Locating the source of odor in a turbulent environment-a common behavior for
      living organisms-is nontrivial because of the random nature of mixing. Here we
      analyze the statistical physics aspects of the problem and propose an efficient
      strategy for olfactory search that can work in turbulent plumes. The algorithm
      combines the maximum likelihood inference of the source position with an active
      search. Our approach provides the theoretical basis for the design of olfactory
      robots and the quantitative tools for the analysis of the observed olfactory
      search behavior of living creatures (e.g., odor-modulated optomotor anemotaxis of
      moths).

PMID- 12228726
TI  - Structural rearrangements in single ion channels detected optically in living
      cells.
AB  - Total internal reflection fluorescence microscopy was used to detect single
      fluorescently labeled voltage-gated Shaker K(+) channels in the plasma membrane
      of living cells. Tetramethylrhodamine (TMR) attached to specific amino acid
      positions in the voltage-sensing S4 segment changed fluorescence intensity in
      response to the voltage-driven protein motions of the channel. The voltage
      dependence of the fluorescence of single TMRs was similar to that seen in
      macroscopic epi-illumination microscopy, but the exclusion of nonchannel
      fluorescence revealed that the dimming of TMR upon voltage sensor rearrangement
      was much larger than previously thought, and is due to an extreme, approximately
      20-fold suppression of the elementary fluorescence. The total internal reflection
      voltage-clamp method reveals protein motions that do not directly open or close
      the ion channel and which have therefore not been detected before at the single
      channel level. The method should be applicable to a wide assortment of membrane
      associated proteins and should make it possible to relate the structural
      rearrangements of single proteins to simultaneously measured physiological cell
      signaling events.

PMID- 12228728
TI  - Donor-bridge-acceptor energetics determine the distance dependence of electron
      tunneling in DNA.
AB  - Electron transfer (ET) processes in DNA are of current interest because of their
      involvement in oxidative strand cleavage reactions and their relevance to the
      development of molecular electronics. Two mechanisms have been identified for ET
      in DNA, a single-step tunneling process and a multistep charge-hopping process.
      The dynamics of tunneling reactions depend on both the distance between the
      electron donor and acceptor and the nature of the molecular bridge separating the
      donor and acceptor. In the case of protein and alkane bridges, the distance
      dependence is not strongly dependent on the properties of the donor and acceptor.
      In contrast, we show here that the distance decay of DNA ET rates varies markedly
      with the energetics of the donor and acceptor relative to the bridge.
      Specifically, we find that an increase in the energy of the bridge states by 0.25
      eV (1 eV = 1.602 x 10(-19) J) relative to the donor and acceptor energies for
      photochemical oxidation of nucleotides, without changing the reaction free
      energy, results in an increase in the characteristic exponential distance decay
      constant for the ET rates from 0.71 to 1.1 A(-1). These results show that, in the
      small tunneling energy gap regime of DNA ET, the distance dependence is not
      universal; it varies strongly with the tunneling energy gap. These DNA ET
      reactions fill a "missing link" or transition regime between the large barrier
      (rapidly decaying) tunneling regime and the (slowly decaying) hopping regime in
      the general theory of bridge-mediated ET processes.

PMID- 12228729
TI  - Memory effects and oscillations in single-molecule kinetics.
AB  - An exactly solvable model for single-molecule kinetics is suggested, based on the
      following assumptions: (i) A single molecule can exist in different chemical
      states and the random transitions from one chemical state to another can be
      described by a local master equation with time-dependent transition rates. (ii)
      Because of conformational and other intramolecular fluctuations the rate
      coefficients in the master equation are random functions of time; their
      stochastic properties are represented in terms of a set of control parameters. We
      assume that the fluctuating rate coefficients fulfill a separability condition,
      that is, they are made up of the multiplicative contributions of two factors: (a)
      a universal factor, which depends on the vector of control parameters and is the
      same for all chemical transformation processes and (b) process-dependent factors,
      which depend on the initial and final chemical states of the molecule but are
      independent of the control parameters. For systems with two chemical states the
      condition of separability is automatically fulfilled. We introduce an intrinsic
      time scale, which makes it possible to compute theoretically various experimental
      observables, such as the correlation functions of the fluorescent signal. We
      analyze the connections between the condition of separability and detailed
      balance, and discuss the possible cause of chemical oscillations in single
      molecule kinetics. We show that the intrinsic dynamics of the molecule, expressed
      by the fluctuations of the control parameters, may lead to damped oscillations of
      the correlation functions of the fluorescent signal. The influence of the random
      fluctuations on the control parameters may be described by a renormalized master
      equation with nonfluctuating apparent rate coefficients. The apparent rate
      coefficients do not have to obey a condition of detailed balance, even though the
      real rate coefficients do obey such a condition. It follows that the renormalized
      master equation may have damped oscillatory solutions.

PMID- 12228730
TI  - beta 2 nicotinic acetylcholine receptor subunit modulates protective responses to
      stress: A receptor basis for sleep-disordered breathing after nicotine exposure.
AB  - Nicotine exposure diminishes the protective breathing and arousal responses to
      stress (hypoxia). By exacerbating sleep-disordered breathing, this disturbance
      could underpin the well established association between smoking and the increased
      risk of sudden infant death syndrome. We show here that the protective responses
      to stress during sleep are partially regulated by particular nicotinic
      acetylcholine receptors (nAChRs). We compared responses of sleeping wild-type and
      mutant mice lacking the beta2 subunit of the nAChR to episodic hypoxia. Arousal
      from sleep was diminished, and breathing drives accentuated in mutant mice
      indicating that these protective responses are partially regulated by beta2
      containing nAChRs. Brief exposure to nicotine significantly reduced breathing
      drives in sleeping wild-type mice, but had no effect in mutants. We propose that
      nicotine impairs breathing (and possibly arousal) responses to stress by
      disrupting functions normally regulated by beta2-containing, high-affinity
      nAChRs.

PMID- 12228731
TI  - Functional interaction of endothelial nitric oxide synthase with a voltage
      dependent anion channel.
AB  - Endothelium-derived nitric oxide (NO) is an important regulator of vascular
      function. NO is produced by endothelial NO synthase (eNOS) whose function is
      modulated, in part, by specific protein interactions. By coimmunoprecipitation
      experiments followed by MS analyses, we identified a human voltage-dependent
      anion/cation channel or porin as a binding partner of eNOS. The interaction
      between porin and eNOS was demonstrated by coimmunoprecipitation studies in
      nontransfected human endothelial cells and Cos-7 cells transiently transfected
      with eNOS and porin cDNAs. In vitro binding studies with glutathione S
      transferase-porin indicated that porin binds directly to eNOS and that this
      interaction augmented eNOS activity. The calcium ionophore, and bradykinin, which
      are known to activate eNOS, markedly increased porin-eNOS interaction, suggesting
      a potential role of intracellular Ca(2+) in mediating this interaction. Theses
      results indicate that the interaction between a voltage-dependent membrane
      channel and eNOS may be important for regulating eNOS activity.

PMID- 12228732
TI  - Interaction of adjacent primase domains within the hexameric gene 4 helicase
      primase of bacteriophage T7.
AB  - The interaction of primase monomers within the hexameric gene 4 helicase-primase
      of bacteriophage T7 has been examined by using two genetically distinct gene 4
      proteins. The T7 56-kDa gene 4 protein differs from the full-length 63-kDa
      protein in that it lacks the N-terminal zinc motif essential for the recognition
      of primase recognition sites. A second gene 4 protein, gp4-K122A, is unable to
      catalyze the synthesis of phosphodiester bonds as the result of an amino acid
      change in the catalytic site. Although each protein alone is inactive, the two
      together catalyze the synthesis of RNA primers. Reconstitution of activity
      depends on hexamer formation. We propose that the zinc motif of one subunit in
      the hexamer interacts with the catalytic sites of adjacent subunits.

PMID- 12228752
TI  - The spectrum of genitourinary malignancies.

PMID- 12228733
TI  - Mitochondrial respiratory control is lost during growth factor deprivation.
AB  - The ability of cells to maintain a bioenergetically favorable ATP/ADP ratio
      confers a tight balance between cellular events that consume ATP and the rate of
      ATP production. However, after growth factor withdrawal, the cellular ATP/ADP
      ratio declines. To investigate these changes, mitochondria from growth factor
      deprived cells isolated before the onset of apoptosis were characterized in
      vitro. Mitochondria from growth factor-deprived cells have lost their ability to
      undergo matrix condensation in response to ADP, which is accompanied by a failure
      to perform ADP-coupled respiration. At the time of analysis, mitochondria from
      growth factor-deprived cells were not depleted of cytochrome c and cytochrome c
      dependent respiration was unaffected, demonstrating that the inhibition of the
      respiratory rate is not due to loss of cytochrome c. Agents that disrupt the
      mitochondrial outer membrane, such as digitonin, or maintain outer membrane
      exchange of adenine nucleotide, such as Bcl-x(L), restored ADP-dependent control
      of mitochondrial respiration. Together, these data suggest that the regulation of
      mitochondrial outer membrane permeability contributes to respiratory control.

PMID- 12228753
TI  - Current status of retroperitoneal lymph node dissection and testicular cancer:
      when to operate.
AB  - BACKGROUND: Historically, retroperitoneal lymph node dissection (RPLND) has been
      used in the therapy of both low-stage and high-stage testicular cancer after
      chemotherapy. As other therapies have developed, the role of RPLND has also
      evolved. METHODS: The authors review the current indications for RPLND in the
      therapy of testicular cancer. RESULTS: Metastatic testicular cancer can be cured
      in 50% to 75% of cases by surgical removal using RPLND, depending on the volume
      of metastasis. In postchemotherapy disease, the surgical removal of teratoma or
      carcinoma also confers a therapeutic benefit to the patient. CONCLUSIONS: The
      therapeutic capability of RPLND in low-stage testicular cancer is
      underappreciated. In postchemotherapy disease, this therapeutic capability is
      retained if the patient has carcinoma or teratoma in the metastatic tumor. In
      postchemotherapy disease, efforts continue to appropriately select patients
      preoperatively who have only fibrosis and necrosis in the specimen and therefore
      do not derive therapeutic benefit from RPLND.

PMID- 12228754
TI  - Surgical management of bladder carcinoma.
AB  - BACKGROUND: Despite advances in medical oncology, radiation therapy, and
      molecular and cell biology, the mainstay in the management of bladder cancer
      continues to be surgery. METHODS: The authors reviewed the literature regarding
      the endoscopic diagnosis and management of bladder cancer as well the role of
      partial and radical cystectomy. RESULTS: Cystoscopy and transurethral resection
      are required to diagnose and stage bladder cancer. The indications for random
      bladder biopsies, prostatic urethral biopsy, and re-resection of the tumor bed
      are examined. The results and complications of endoscopic resection in the
      management of Ta, T1, and T2 or greater bladder cancer are reported. The roles of
      partial cystectomy, radical cystectomy, extent of lymphadenectomy, and
      indications for urethrectomy are also examined. The results and complications of
      radical cystectomy for the management of T2, T3, T4, and N+ bladder cancer are
      reported. CONCLUSIONS: Surgery remains a critical element in the management of
      bladder cancer. Improvements in surgical technique, urinary reconstruction, and
      multimodal therapy continue to improve the prognosis and quality of life of
      patients with transitional cell cancer of the bladder.

PMID- 12228755
TI  - Immunotherapy of metastatic renal cell cancer.
AB  - BACKGROUND: The management of metastatic renal cancer remains a therapeutic
      challenge. Conventional cytotoxic chemotherapy is rarely effective, and the most
      promising approaches appear to lie in the field of immunotherapy. METHODS: The
      authors review the literature regarding current and investigational immunotherapy
      approaches to the management of metastatic renal cancer. RESULTS: The mechanism
      of action, methods of delivery, efficacy, and side effect profile of the
      cytokines IL-2 and interferon alfa are discussed. The role of investigational
      approaches such as tumor vaccines, antibody-based therapy, lymphocyte infusions,
      and bone marrow transplantation is addressed. The rationale for nephrectomy as an
      adjunctive procedure to immunotherapy is also discussed. CONCLUSIONS: Ongoing
      laboratory investigation of the cause of the immune deficit in patients with
      metastatic renal cell cancer will result in the development of novel therapies to
      enhance tumor cell recognition as well as host antitumor response. Translation of
      laboratory findings into the clinic will be facilitated by the presence of an
      already well-developed infrastructure for the performance of clinical trials for
      patients with this difficult diagnosis.

PMID- 12228756
TI  - Cancer of the penis.
AB  - BACKGROUND: Cancer of the penis is an uncommon malignancy in developed countries,
      but the incidence is as high as 17% of all male cancers in some undeveloped
      countries. The surgical management of this disease has improved due to better
      knowledge of risk for metastasis and newer imaging technologies to assess the
      regional lymph nodes. METHODS: We review the literature on incidence, etiology,
      pathology, clinical presentation, staging, and management of penile cancer. We
      present our institutional experience with 160 patients who underwent extended
      ilioinguinal lymph node dissection, as well as with 7 patients who underwent a
      modified lymph node dissection. RESULTS: Better understanding of pathologic
      features allow for stratification of patients into low, intermediate, or high
      risk for lymph node involvement. Lymphatic mapping to this stratification
      improves selection of patients who might benefit from lymph node dissection after
      excision of the primary lesion. Our experience with lymph node dissection yielded
      a high incidence of positive lymph nodes when lymphadenopathy was present. The
      recent use of a modified lymph node dissection has minimized morbidity. Current
      chemotherapy agents are ineffective in this disease. CONCLUSIONS: Pathologic
      features of the primary lesion and the incorporation of lymphatic mapping have
      improved the selection of patients who might benefit from lymph node dissection.
      The use of a modified lymph node dissection in selected patients has decreased
      morbidity. Effective chemotherapy agents are needed in the management of advanced
      penile cancer.

PMID- 12228757
TI  - Controversies surrounding androgen deprivation for prostate cancer.
AB  - BACKGROUND: Management of metastatic prostate cancer continues to evolve. The
      widespread use of the prostate-specific antigen (PSA) assay has led to earlier
      diagnosis and earlier detection of recurrent disease. Debates continue regarding
      the proper use and timing of endocrine therapy with orchiectomy, estrogen
      agonists, luteinizing hormone-releasing hormone (LHRH) analogs, LHRH antagonists,
      and androgen antagonists. METHODS: The authors reviewed the significant published
      materials of the last 20 years that have shaped hormonal management of metastatic
      and progressive prostate cancer. Major areas of controversy were also identified.
      RESULTS: The present approach to hormonal management is summarized. Five
      potential pathways to the development of androgen-independent prostate cancer are
      described. Controversial topics of hormonal management, including immediate vs
      delayed hormonal therapy, monotherapy vs maximal androgen blockade (MAB), and
      intermittent hormonal therapy, are discussed. CONCLUSIONS: Orchiectomy, estrogen
      agonists, and LHRH analogs have therapeutic equivalence. Patients who have a
      rising PSA after definitive treatment for prostate cancer and high risk of
      recurrent disease may warrant early androgen deprivation. MAB does not appear to
      be significantly better than single-agent LHRH analog therapy. Intermittent
      therapy may delay emergence of androgen independence and maintain or improve
      quality of life.

PMID- 12228758
TI  - Evaluation and management of adrenal masses.
AB  - BACKGROUND: The widespread use of abdominal imaging has led to increased
      detection of adrenal tumors. The significance of these masses, as well as the
      optimal management approach to treatment, has generated some controversy
      regarding further evaluation and therapy. METHODS: The authors reviewed the
      literature regarding the evaluation and management of these masses, particularly
      adrenal incidentalomas. Based on their institutional experience, they propose a
      diagnostic, evaluation, and management algorithm for treating adrenal masses.
      RESULTS: Appearance and clinical history should indicate how to perform the
      biochemical evaluation, keeping in mind that the presence of pheochromocytomas
      must be ruled out. Radiological evaluation by CT or MRI provides useful
      parameters to identify malignant lesions. Surgery is indicated for masses that
      are larger than 5 cm in diameter or suspected of malignancy. Fine-needle
      aspiration biopsy should be used when other extra-adrenal malignancies are
      suspected and after pheochromocytoma has been ruled out. CONCLUSIONS: Careful
      analysis of each adrenal mass is essential to effectively avoid potential
      problems. Guidelines to manage patients with adrenal masses are needed.

PMID- 12228759
TI  - Positron emission tomography in urologic oncology.
AB  - BACKGROUND: Positron emission tomography (PET) is an emerging imaging modality
      that is being investigated for use in urologic oncology. PET scanning using the
      radioactive glucose analog FDG has proven to be a highly accurate imaging test
      for diagnosing and staging a variety of non-urologic cancer types. This review
      was performed to determine the role of PET imaging in genitourinary malignancies.
      METHODS: A review of the literature focusing on PET and urologic oncology was
      performed. The role of PET imaging was reviewed in prostate, bladder, renal, and
      testicular cancer. RESULTS: In testicular cancer, PET has a higher diagnostic
      accuracy than computed tomography (CT) for both staging and re-staging and should
      be the test of choice for the assessment of a CT-visualized residual mass
      following chemotherapy. In prostate, renal, and bladder cancer, the current role
      of PET is still being defined, but it has a high positive predictive value and
      can be used for problem solving in patients with indeterminate findings on
      conventional imaging. Its role in the diagnosis and staging of prostate cancer is
      hampered by the generally low glycolytic rate of most prostate tumors and their
      metastases. It has shown promise for staging and re-staging patients with
      advanced-stage disease and aggressive tumors suspected by a high tumor grade and
      high prostate-specific antigen velocity. PET has also demonstrated success when
      applied to renal cell carcinoma in classifying indeterminate renal masses as well
      as residual renal fossa masses following nephrectomy, gauging response to
      therapy, and staging and re-staging patients with a known diagnosis of renal cell
      carcinoma. CONCLUSIONS: PET imaging has demonstrated great potential in certain
      applications, but further investigations are necessary to determine its eventual
      place as an imaging modality in genitourinary malignancies.

PMID- 12228760
TI  - Conventional chest radiography in the initial assessment of adult cancer patients
      with fever and neutropenia.

PMID- 12228761
TI  - Markers of alcohol abuse.

PMID- 12228762
TI  - Redox signal transduction: reductive reasoning.
AB  - The activation of receptors has been believed to be due to a conformational
      change that occurs when the agonist "locks" into the receptor. However, evidence
      suggests that several receptors are activated by redox reactions, which occur
      when an agonist binds with the receptor. The stereochemistry of the receptor
      likely provides specificity to the electron transfer by determining which agonist
      can bind to the receptor. The resulting signal, in some cases, may then be
      transferred across the membrane by G-proteins, which also are redox-coupled. This
      concept puts receptors into the large group of cell functions that are redox
      regulated. Other systems for which evidence of redox regulation occurs include
      ion pumps and channels, as well as transcription factors.

PMID- 12228763
TI  - Formation of phosphatidylethanol in vitro in red blood cells from healthy
      volunteers and chronic alcoholics.
AB  - Phosphatidylethanol (PEth) is an abnormal phospholipid, formed only in the
      presence of ethanol via a transphosphatidylation reaction of phospholipase D
      (PLD). PEth in blood is a promising new marker of alcohol abuse. Blood PEth is
      found almost exclusively in red cells. This study was performed to investigate a
      possible PEth formation in human red cells from alcoholics and healthy
      individuals, at physiologically relevant ethanol concentrations. Blood was drawn
      from six healthy volunteers (controls) and six chronic inpatient alcoholics.
      Hematological analyses were performed, and red blood cells were separated and
      incubated in plasma with ethanol to study PEth formation. Lipids were extracted
      and PEth analyzed with high pressure liquid chromatography and evaporative light
      scattering detection. Incubation of red cells in 50 mM ethanol yielded detectable
      PEth after 12 hours. Formation of PEth was concentration dependent at 10 to 50 mM
      ethanol. In vitro formation of PEth was significantly higher (P <.001) in red
      cells from alcoholics (5.2 +/- 1.1 micromol/l) compared to controls (2.4 +/- 0.6
      micromol/l) (mean +/- SD). A significant correlation (P <.01) was observed
      between initial mean corpuscular volume and accumulated PEth. This study
      demonstrates that PEth is formed in human red cells at physiologically relevant
      ethanol concentrations. Alcoholics accumulate about twice as much PEth than
      controls. The accumulation rate of PEth is slower in red cells compared to rates
      reported for other tissues.

PMID- 12228764
TI  - Cyclosporin A and FK506 decrease adenosine kinase activity and adenosine uptake
      in T-lymphocytes.
AB  - Adenosine is a potent modulator of immune function, and adenosine kinase (AK), a
      rate-limiting enzyme for adenosine uptake and metabolism, is a potential mediator
      of adenosine regulation. We have found that adenosine uptake increased six- to 18
      fold during T-lymphocyte activation. This increase correlated with an increase in
      AK activity but not in AK protein. The immunosuppressive drugs cyclosporin A
      (CsA) and FK506 inhibited both adenosine uptake and AK activity in a
      concentration-dependent manner. Among several nucleosides and bases, the
      inhibition of uptake was selective for adenosine. Immunosuppressive drug
      treatment also caused a twofold increase in the level of extracellular adenosine
      but not of inosine, suggesting that the effect is not related to the general
      toxicity of drugs. Inhibitors of calcineurin did not inhibit adenosine uptake,
      suggesting that this protein phosphatase does not mediate the effect. These data
      demonstrate that CsA and FK506 enhance adenosine concentrations in T-lymphocytes
      by way of a mechanism that involves AK inhibition.

PMID- 12228765
TI  - Activation of prostaglandin E2-receptor EP2 and EP4 pathways induces growth
      inhibition in human gastric carcinoma cell lines.
AB  - The effect of prostaglandin E2 (PGE2) on the proliferation of gastric cancer
      cells is still unclear. PGE2 receptors are divided into four subtypes - EP1, EP2,
      EP3, and EP4 - which are coupled to three different intracellular signal
      transduction systems. Stimulation of EP2 and EP4 is linked with cyclic adenosine
      3', 5'-monophosphate (cAMP)-dependent protein kinase A (PKA). In some human
      gastric cancer cells, PGE2 has been suggested to have an antiproliferative effect
      by way of increased cAMP production. Expression of EP2 and EP4 in human gastric
      carcinoma cells, however, has not been examined. We examined the expression of
      EP2 and EP4 and the antiproliferative effects of specific EP2 and EP4 agonists on
      four different human gastric cancer cell lines. Our data clarified that all the
      cell lines investigated in this study expressed EP2 and EP4 and that the specific
      agonists of these receptors induced growth inhibition with an accompanying
      increase in cAMP production. In summary, gastric cancer cells have EP2 and EP4
      receptors, and their selective activation is linked with the decreased cell
      proliferation.

PMID- 12228766
TI  - Captopril-impaired production of tumor necrosis factor-alpha-induced interleukin
      1beta in human monocytes is associated with altered intracellular distribution of
      nuclear factor-kappaB.
AB  - We evaluated the effects of the angiotensin-converting enzyme (ACE) inhibitor
      captopril on pathways for monocyte production of interleukin (IL)-1beta in vitro.
      Human monocytes were treated with captopril and stimulated with tumor necrosis
      factor (TNF)-alpha or lipopolysaccharide. Captopril caused a dose-dependent
      reduction of TNF-alpha induced IL-1beta. LPS-induced IL-1beta generation was not
      reduced by the ACE inhibitor. Pro-IL-1beta concentrations followed the same
      pattern as that for mature IL-1beta when monocytes were preincubated with
      captopril. Also, IL-1beta mRNA concentrations were reduced by captopril
      pretreatment in parallel with IL-1beta. We sought to determine whether captopril
      affected the nuclear factor (NF)-kappaB complex in monocytic cells. We found that
      the translocation of the p-65 component of NF-kappaB to the nucleus was inhibited
      by captopril. Thus captopril reduced TNF-alpha-induced IL-1beta and IL-1betamRNA
      synthesis in monocytes, in vitro, probably through interference with NF-kappaB
      activation of the IL-1beta gene. These results support the hypothesis that
      captopril has immunomodulating properties.

PMID- 12228767
TI  - Association between serum total and lipid-bound sialic acid concentration and the
      severity of coronary atherosclerosis.
AB  - Serum total sialic acid has recently been shown to be a cardiovascular risk
      factor. Increased levels of this substance are associated with higher
      cardiovascular mortality and with cerebrovascular disease. It has also been shown
      that serum concentrations of total and lipid-associated sialic acid are
      significantly increased in hypertriglyceridemia. On the other hand, several
      circulating lipoproteins have been suggested to be related to the severity of
      coronary atherosclerosis, but contradictory results have been reported in the
      possible relationship between the concentrations of sialic acid and the severity
      of coronary lesions in patients with coronary heart disease. The purpose of this
      study was to investigate the possible relationship between serum total sialic
      acid concentration, recently shown to be a cardiovascular risk factor, and serum
      lipid-bound sialic acid concentration and the severity of coronary lesions. The
      study comprised 90 subjects, divided into three subgroups according to
      angiography results: 30 patients with no vessel disease, 30 patients with single
      vessel disease, and 30 patients with double/triple-vessel disease. Serum total
      sialic acid determination was carried out with the thiobarbituric acid method of
      Warren; lipid-associated sialic acid was assayed with the method of Katopodis.
      Mean serum total sialic acid levels in patients with single-vessel disease (P
      <.05) and patients with double/triple-vessel disease (P <.001) were found to be
      significantly increased compared with that in patients with no vessel disease,
      whereas mean serum lipid-bound sialic acid levels were found to be significantly
      different between patients with double- or triple-vessel disease and patients
      with no vessel disease (P <.001). We also noted a significant difference between
      the levels of serum total sialic acid (P <.001) and lipid-bound sialic acid (P
      <.001) in patients with single-vessel disease and patients with double/triple
      vessel disease. We found a significant correlation only between serum lipid-bound
      sialic acid and coronary angiographic score in patients with double/triple-vessel
      disease (r = 0.425, P <.05). Although the concentration of serum total sialic
      acid is increased proportionally with the number of diseased coronary arteries,
      only the concentration of serum lipid-bound sialic acid is related to the
      severity of coronary atherosclerosis, especially in patients with double/triple
      vessel disease.

PMID- 12228768
TI  - Short-term administration of basic fibroblast growth factor enhances coronary
      collateral development without exacerbating atherosclerosis and balloon injury
      induced vasoproliferation in atherosclerotic rabbits with acute myocardial
      infarction.
AB  - We evaluated the effect of basic fibroblast growth factor (bFGF) on the extent of
      atherosclerosis and balloon injury-induced vasoproliferation in atherosclerotic
      animals with acute myocardial infarction (AMI). Fifty-six rabbits were fed a 1%
      cholesterol diet. Balloon injury of iliac arteries and experimental acute
      myocardial infarction were induced in the same animals. Rabbits were then
      randomized to a bFGF group (20 pg/day, intravenously) or a control group
      (intravenous saline solution). The beneficial effects of bFGF on cardiac
      function, infarct size, and collateral vessel development, and the possible
      effect on vasoproliferation of balloon-injured vessels, were measured after 1 and
      2 weeks. The extent of atherosclerosis was measured after 1, 2, and 4 weeks. Our
      results showed that bFGF significantly reduced infarct size and increased
      collateral-vessel density (P <.01) in infarct areas. Cardiac function was better
      in the bFGF group than in corresponding controls (P <.05). Similar beneficial
      effects of bFGF were noted in animals after 1- and 2-week treatments. However,
      the extent of atherosclerosis and the vasoproliferation in chronic
      atherosclerotic vessels induced by balloon injury and cholesterol diet were not
      significantly different between the two groups. Our results suggest that short
      term treatment with bFGF enhances collateral development and produces maximum
      therapeutic benefits without exacerbating atherosclerosis and cell proliferation
      in stenotic vessels after AMI in atherosclerotic rabbits.

PMID- 12228769
TI  - James Herrick, sickle cell disease, and the thrombogenic theory of myocardial
      infarction.

PMID- 12228770
TI  - Secondary mitral and tricuspid regurgitation accompanying left ventricular
      systolic dysfunction: is it important, and how is it treated?

PMID- 12228771
TI  - Reperfusion in waiting: what queue should we join?

PMID- 12228772
TI  - Demise of the routine electrophysiologic study for survivors of life-threatening
      ventricular arrhythmias.

PMID- 12228773
TI  - The Pediatric Randomized Carvedilol Trial in Children with Heart Failure:
      rationale and design.
AB  - BACKGROUND: Carvedilol is a medication with both beta-receptor and alpha-receptor
      blocking properties that has been approved for the treatment of heart failure in
      adults. Little is known about its safety, efficacy, pharmacokinetics, and dosing
      profile in children. METHODS: The primary objective of this study is to evaluate
      the efficacy of carvedilol administered twice daily for 8 months in terms of its
      effect compared with placebo on a composite measure of clinical outcomes in
      children with symptomatic systemic ventricular systolic dysfunction and heart
      failure. The secondary objectives are to determine the effect of carvedilol on
      individual components of a composite of clinical outcomes (hospitalizations for
      worsening heart failure, all-cause mortality and cardiovascular hospitalizations,
      all cause mortality, heart failure symptoms, and patient and physician global
      assessment); determine the effect of carvedilol on echocardiographic indices of
      ventricular function and remodeling; characterize the pharmacokinetics of
      carvedilol in pediatric patients with heart failure; characterize the effects
      carvedilol on neurohormonal systems; and provide data for the selection of an
      optimal titration schedule and daily dose of carvedilol in children with heart
      failure. This study will enroll 150 children between birth and 17 years of age
      with chronic symptomatic heart failure caused by systemic ventricular systolic
      dysfunction. CONCLUSION: This study will determine whether carvedilol improves
      symptoms in children with heart failure as a result of systemic ventricular
      systolic dysfunction. The study also will provide information on
      echocardiographic changes of ventricular performance and neurohormonal levels in
      children with heart failure before and after treatment with carvedilol, in
      addition to pharmacokinetics of carvedilol in children.

PMID- 12228774
TI  - Risk of sudden versus nonsudden cardiac death in patients with coronary artery
      disease.
AB  - BACKGROUND: Patients at high risk of sudden cardiac death, yet at low risk of
      nonsudden death, might be ideal candidates for antiarrhythmic drugs or devices.
      Most previous studies of prognostic markers for sudden cardiac death have ignored
      the competitive risk of nonsudden cardiac death. The goal of the present study
      was to evaluate the ability of clinical factors to distinguish the risks of
      sudden and nonsudden cardiac death. METHODS: We identified all deaths during a
      3.3-year follow-up of 30,680 patients discharged alive after admission to the
      cardiac care unit of a Seattle hospital. Detailed chart reviews were conducted on
      1093 subsequent out-of-hospital sudden deaths, 973 nonsudden cardiac deaths, and
      442 randomly selected control patients. RESULTS: Patients who died in follow-up
      (suddenly or nonsuddenly) were significantly different for many clinical factors
      from control patients. In contrast, patients with sudden cardiac death were
      insignificantly different for most clinical characteristics from patients with
      nonsudden cardiac death. The mode of death was 20% to 30% less likely to be
      sudden in women, patients who had angioplasty or bypass surgery, and patients
      prescribed beta-blockers. The mode of death was 20% to 30% more likely to be
      sudden in patients with heart failure, frequent ventricular ectopy, or a
      discharge diagnosis of acute myocardial infarction. A multivariable model had
      only modest predictive capacity for mode of death (c-index of 0.62). CONCLUSION:
      Standard clinical evaluation is much better at predicting overall risk of death
      than at predicting the mode of death as sudden or nonsudden.

PMID- 12228775
TI  - Utilization and outcomes of the implantable cardioverter defibrillator, 1987 to
      1995.
AB  - BACKGROUND: The patterns of adoption of the implantable cardioverter
      defibrillator (ICD) and the outcomes of its use have not been well documented in
      general, unselected populations. The purpose of this study was to document the
      impact of the ICD in widespread clinical practice. METHODS: We identified ICD
      recipients by use of the hospital discharge databases of Medicare beneficiaries
      for 1987 through 1995 and of California residents for 1991 through 1995. The
      index admission for each patient was linked to previous and subsequent admissions
      and to mortality files to create a longitudinal patient profile. RESULTS: The
      rate of ICD implantations increased >10-fold between 1987 and 1995, as both the
      number of hospitals performing the procedure and the volume of ICD implantations
      per hospital rose. Mortality rates within 30 days of ICD implantation decreased
      from 6.0% to 1.9%, and mortality rates within 1 year fell from 19.3% to 11.4%.
      Surgical interventions to revise or replace the ICD within the first year
      remained about 5%, however, and cumulative expenditures at 1 year ($46,000
      $51,000) changed very little. ICD implantation rates varied >3-fold among
      different regions of the United States. CONCLUSIONS: ICD use has expanded
      markedly during the study period, with improved mortality rates, but medical
      expenditures and rates of surgical revision remain high for ICD recipients.

PMID- 12228776
TI  - Life after a ventricular arrhythmia.
AB  - BACKGROUND: There are few data from community-based evaluations of outcomes after
      a life-threatening ventricular arrhythmia (LTVA). We evaluated patients' quality
      of life (QOL) and medical costs after hospitalization and treatment for their
      first episode of an LTVA. METHODS: We prospectively evaluated QOL by use of the
      Duke Activity Status Index (DASI), Medical Outcomes Study SF-36 mental health and
      vitality scales, the Cardiac Arrhythmia Suppression Trial (CAST) symptom scale,
      and resource use in patients discharged after a first episode of an LTVA in a
      managed care population of 2.4 million members. RESULTS: We enrolled 264 subjects
      with new cases of LTVA. Although functional status initially decreased compared
      with self-reports of pre-event functional status, both functional status and
      symptom levels improved significantly during the study period. These improvements
      were greater in patients receiving an implantable cardioverter defibrillator
      (ICD) than in patients receiving amiodarone. Ratings of mental health and
      vitality were not significantly different between the treatment groups and did
      not change significantly during follow-up. The total 2-year medical costs were
      higher for patients receiving an ICD than for patients receiving amiodarone,
      despite lower costs during the follow-up period for the patients receiving an
      ICD. CONCLUSIONS: New onset of an LTVA has a substantial negative initial impact
      on QOL. With therapy, most patients have improvements in their QOL and symptom
      level, possibly more so after treatment with an ICD. The costs of treating these
      patients are very high.

PMID- 12228777
TI  - Trends in hospital treatment of ventricular arrhythmias among Medicare
      beneficiaries, 1985 to 1995.
AB  - BACKGROUND: Treatment options for patients with ventricular arrhythmias have
      undergone major changes in the last 2 decades. Trends in use of invasive
      procedures, clinical outcomes, and expenditures have not been well documented.
      METHODS: We used administrative databases of Medicare beneficiaries from 1985 to
      1995 to identify patients hospitalized with ventricular arrhythmias. We created a
      longitudinal patient profile by linking the index admission with all earlier and
      subsequent admissions and with death records. RESULTS: Approximately 85,000
      patients aged > or =65 years went to hospitals in the United States with
      ventricular arrhythmias each year, and about 20,000 lived to admission. From 1987
      to 1995, the use of electrophysiology studies and implantable cardioverter
      defibrillators in patients who were hospitalized grew substantially, from 3% to
      22% and from 1% to 13%, respectively. Hospital expenditures rose 8% per year,
      primarily because of the increased use of invasive procedures. Survival improved,
      particularly in the medium term, with 1-year survival rates increasing between
      1987 and 1994 from 52.9% to 58.3%, or half a percentage point each year.
      CONCLUSION: Survival of patients who sustain a ventricular arrhythmia is poor,
      but improving. For patients who are admitted, more intensive treatment has been
      accompanied by increased hospital expenditures.

PMID- 12228778
TI  - Overview of randomized trials of antiarrhythmic drugs and devices for the
      prevention of sudden cardiac death.
AB  - BACKGROUND: Sudden cardiac death is a prominent feature of the natural history of
      heart disease. The efficacy of antiarrhythmic drugs and devices in preventing
      sudden death and reducing total mortality is uncertain. METHODS: We reviewed
      randomized trials and quantitative overviews of type I and type III
      antiarrhythmic drugs. We also reviewed the randomized trials of implantable
      cardioverter defibrillators and combined these outcomes in a quantitative
      overview. RESULTS: Randomized trials of type I antiarrhythmic agents used as
      secondary prevention after myocardial infarction show an overall 21% increase in
      mortality rate. Randomized trials of amiodarone suggest a 13% to 19% decrease in
      mortality rate, and sotalol has been effective in several small trials. Trials of
      pure type III agents, however, have shown no mortality benefit. An overview of
      implantable defibrillator trials shows a 24% reduction in mortality rate (CI 15%
      33%) compared with alternative therapy, most often amiodarone. CONCLUSION:
      Amiodarone is effective in reducing the total mortality rate by 13% to 19%, and
      the implantable defibrillator reduces the mortality rate by a further 24%.

PMID- 12228779
TI  - Management of ventricular arrhythmias in diverse populations in California.
AB  - BACKGROUND: The use of coronary angiography and revascularization is lower than
      expected among black patients. It is uncertain whether use of other cardiac
      procedures also varies according to race and ethnicity and whether outcomes are
      affected. METHODS: We analyzed discharge abstracts from all nonfederal hospitals
      in California of patients hospitalized for a primary diagnosis of ventricular
      tachycardia or ventricular fibrillation between 1992 and 1994. We compared
      mortality rates and use of electrophysiologic study (EPS) and implantable
      cardioverter-defibrillator (ICD) procedures according to the race and ethnicity
      of the patient. RESULTS: Among 8713 patients admitted with ventricular
      tachycardia or ventricular fibrillation, 29% (n = 2508) had a subsequent EPS
      procedure, and 9% (n = 818) had an ICD implanted. After controlling for potential
      confounding factors, we found that black patients were significantly less likely
      than white patients to undergo EPS (odds ratio 0.72, CI 0.56-0.92) or ICD
      implantation (odds ratio 0.39, CI 0.25-0.60). Blacks discharged alive from the
      initial hospital admission had higher mortality rates over the next year than
      white patients, even after controlling for multiple confounding risk factors
      (risk ratio 1.18, CI 1.03-1.36). The use of EPS and ICD procedures was also
      significantly affected by several other factors, most notably by on-site
      procedure availability but also by age, sex, and insurance status. CONCLUSIONS:
      In a large population of patients hospitalized for ventricular arrhythmia, blacks
      had significantly lower rates of utilization for EPS and ICD procedures and
      higher subsequent mortality rates.

PMID- 12228780
TI  - Effect of risk stratification on cost-effectiveness of the implantable
      cardioverter defibrillator.
AB  - BACKGROUND: Implantable cardioverter defibrillators (ICDs) effectively prevent
      sudden cardiac death, but selection of appropriate patients for implantation is
      complex. We evaluated whether risk stratification based on risk of sudden cardiac
      death alone was sufficient to predict the effectiveness and cost-effectiveness of
      the ICD. METHODS: We developed a Markov model to evaluate the cost-effectiveness
      of ICD implantation compared with empiric amiodarone treatment. The model
      incorporated mortality rates from sudden and nonsudden cardiac death, noncardiac
      death and costs for each treatment strategy. We based our model inputs on data
      from randomized clinical trials, registries, and meta-analyses. We assumed that
      the ICD reduced total mortality rates by 25%, relative to use of amiodarone.
      RESULTS: The relationship between cost-effectiveness of the ICD and the total
      annual cardiac mortality rate is U-shaped; cost-effectiveness becomes unfavorable
      at both low and high total cardiac mortality rates. If the annual total cardiac
      mortality rate is 12%, the cost-effectiveness of the ICD varies from $36,000 per
      quality-adjusted life-year (QALY) gained when the ratio of sudden cardiac death
      to nonsudden cardiac death is 4 to $116,000 per QALY gained when the ratio is
      0.25. CONCLUSIONS: The cost-effectiveness of ICD use relative to amiodarone
      depends on total cardiac mortality rates as well as the ratio of sudden to
      nonsudden cardiac death. Studies of candidate diagnostic tests for risk
      stratification should distinguish patients who die suddenly from those who die
      nonsuddenly, not just patients who die suddenly from those who live.

PMID- 12228781
TI  - High-sensitivity C-reactive protein in the prediction of coronary events in
      patients with premature coronary artery disease.
AB  - BACKGROUND AND METHODS: Inflammation plays an important role in the initiation
      and progression of atherosclerosis and in the pathogenesis of acute
      cardiovascular events. Recent studies have indicated a possible association
      between C-reactive protein (CRP) and the clinical outcome of coronary artery
      disease (CAD). We studied prospectively in a group of 125 patients with premature
      CAD whether plasma levels of CRP as measured with a high-sensitivity assay
      predict risk for future coronary events. All patients had stable CAD at time of
      blood sampling but had originally been seen with unstable angina or myocardial
      infarction. The mean follow-up time after blood collection was 54 months, and
      death, myocardial infarction, need for coronary revascularization, or admission
      to hospital with angina pectoris were defined as clinical end points. RESULTS:
      Patients in the highest tertile of CRP levels had a >3.8-fold risk (risk ratio
      3.82, 95% CI 1.19-12.17) for death, myocardial infarction, or need for coronary
      revascularization compared with the patients in the first tertile. The relative
      risk for patients in the second tertile was 3.5-fold higher (95% CI 1.04-11.56).
      CRP levels in the third tertile independently predicted risk after adjustment for
      lipids and other clinical risk factors. CONCLUSION: In patients with clinically
      stable conditions who have a positive history for acute coronary syndromes before
      age 50 years, plasma levels of CRP higher than 1.6 mg/L are predictors of future
      coronary events and therefore indicate the role of underlying chronic
      inflammation for the clinical course of CAD. Accordingly, reference limits for
      prediction of risk in CAD have to be lower in this specific patient group than in
      middle-aged or elderly patients.

PMID- 12228782
TI  - How long is too long? Association of time delay to successful reperfusion and
      ventricular function outcome in acute myocardial infarction: the case for
      thrombolytic therapy before planned angioplasty for acute myocardial infarction.
AB  - OBJECTIVES: The purpose of this study was to quantify the effect of time delays
      to reperfusion on ventricular function after myocardial infarction. This allows
      one to identify a group of patients in whom a strategy using antecedent
      pharmacologic reperfusion therapy before planned direct angioplasty may offer
      significant benefit. BACKGROUND: Direct angioplasty for myocardial infarction is
      associated with a high rate of successful reperfusion compared with pharmacologic
      reperfusion. However, there is an inherent time delay to treatment with
      angioplasty compared with pharmacologic therapy. There currently are insufficient
      data to determine the consequences of incremental time delays to reperfusion on
      ventricular function. METHODS: We determined, by logistic regression analysis,
      the probability of observing a decrement in postmyocardial infarction ventricular
      function as a function of incremental time delays to reperfusion. RESULTS: Time
      delays of 30, 60, 90, or 120 minutes to reperfusion increased the likelihood of a
      worse ventricular function outcome by 1.1-, 1.3-, 1.5-, and 1.7-fold,
      respectively (P <.02). The upper 95% confidence limits around these odds ratios
      are as high as 1.3 or 2.7 for 30- and 120-minute delays, respectively. Time from
      symptom onset to patency remained a significant determinant of ventricular
      function after adjustment for clinical and procedural factors. CONCLUSIONS: Delay
      in time to reperfusion, measured in minutes, results in significant loss of
      ventricular function after myocardial infarction. Interventional strategies
      designed for treatment of myocardial infarction when "door-to-balloon" time is
      expected to exceed 60 minutes should strongly consider incorporation of
      pharmacologic reperfusion therapy into the therapeutic paradigm.

PMID- 12228783
TI  - Inhospital outcome of acute myocardial infarction in patients with prior coronary
      artery bypass surgery.
AB  - OBJECTIVES: Our goals were to compare the characteristics of patients with and
      without prior coronary artery bypass graft (CABG) presenting with acute
      myocardial infarction (MI) with or without ST elevation/left bundle branch block
      (LBBB), and to evaluate the effect of ST shift on inhospital mortality. METHODS
      AND RESULTS: Using the National Registry of Myocardial Infarction-3 Registry, we
      identified 112,697 patients with acute MI without exclusion criteria. Of these,
      15,936 (14.1%) had prior CABG. Patients with prior CABG had more adverse
      characteristics and were less likely to have ST elevation/LBBB than patients
      without prior CABG. The unadjusted mortality for ST elevation/LBBB patients was
      higher in patients with prior CABG versus without (16.2% vs 14.1%, P =.0001),
      whereas in patients without ST elevation/LBBB, prior CABG conferred a lower
      unadjusted mortality versus without (10.1% vs 12.4%, P =.0001). Adjusting for
      baseline differences, prior CABG was weakly associated with inhospital mortality
      in ST elevation/LBBB patients (odds ratio [OR], 1.11, 95% CI 1.00-1.23), but not
      in patients without ST elevation/LBBB (OR 0.99, 95% CI 0.92-1.07). CONCLUSION:
      Acute MI patients with prior CABG are more likely to present without ST
      elevation/LBBB than patients without prior CABG. Prior CABG was weakly associated
      with inhospital mortality in patients with ST elevation/LBBB, but not in patients
      without these electrocardiographic findings. This suggests the differences in
      absolute mortality rates between patients presenting with MI with and without a
      history of prior CABG are largely caused by differences in baseline
      characteristics and presentation.

PMID- 12228784
TI  - Randomized double-blind safety study of enoxaparin versus unfractionated heparin
      in patients with non-ST-segment elevation acute coronary syndromes treated with
      tirofiban and aspirin: the ACUTE II study. The Antithrombotic Combination Using
      Tirofiban and Enoxaparin.
AB  - BACKGROUND: In comparison with treatment with unfractionated heparin (UFH) and
      aspirin (ASA), both tirofiban administered with UFH and ASA, and enoxaparin plus
      ASA have shown superiority in reducing cardiac ischemic events in patients with
      unstable angina and non-ST-segment elevation myocardial infarction. Replacing UFH
      with enoxaparin when tirofiban is administered to patients may offer further
      therapeutic benefit, but could also increase bleeding. OBJECTIVE: Our objective
      was to provide estimates of the frequency of bleeding complications, as defined
      by means of the Thrombolysis In Myocardial Infarction(TIMI) group, and collect
      data on clinical efficacy of the combination of tirofiban with enoxaparin plus
      ASA. METHODS: Five hundred twenty-five patients with UA/NSTEMI were treated with
      tirofiban coadministered with ASA and randomized to receive either UFH (n = 210)
      or enoxaparin (n = 315). Therapy was administered for 24 to 96 hours. Bleeding
      incidences were assessed until 24 hours after trial therapy was discontinued;
      other clinical outcomes were assessed for as long as 30 days. RESULTS: The total
      bleeding rate (TIMI major + minor + loss-no-site) for the UFH group versus the
      enoxaparin group was 4.8% vs 3.5% (odds ratio [OR] 1.4, CI 0.6-3.4). The TIMI
      major and minor bleeding rates for the UFH versus the enoxaparin groups were 1.0%
      versus 0.3% (OR 3.0, CI 0.3-33.8) and 4.3% versus 2.5% (OR 1.7, CI 0.7-4.6).
      There was an increase in nuisance cutaneous and oral bleeds (<50 mL of blood
      loss) in the enoxaparin group. Death or myocardial infarction occurred with
      similar frequency in the 2 groups (9.0% vs 9.2%). However, refractory ischemia
      requiring urgent revascularization and rehospitalization because of unstable
      angina occurred more frequently in the UFH group (4.3% vs 0.6% and 7.1% vs 1.6%,
      respectively). CONCLUSIONS: Combination therapy with tirofiban plus enoxaparin
      appears safe, relative to therapy with tirofiban plus UFH.

PMID- 12228785
TI  - Prognostic value of baseline electrophysiology studies in patients with sustained
      ventricular tachyarrhythmia: the Antiarrhythmics Versus Implantable
      Defibrillators (AVID) trial.
AB  - OBJECTIVES: We sought to determine the value of electrophysiology (EP) testing in
      patients with ventricular fibrillation (VF), ventricular tachycardia (VT) with
      syncope, or sustained VT in the setting of left ventricular dysfunction.
      BACKGROUND: Traditionally, EP testing is part of the workup of patients with
      sustained VT or VF. Recently, some have suggested that EP testing is unnecessary
      in these patients, many of whom are likely to receive an implantable cardioverter
      defibrillator (ICD). METHODS: Within a multicenter trial (Antiarrhythmics Versus
      Implantable Defibrillators) designed to evaluate whether drugs or ICD resulted in
      a better outcome, data were analyzed regarding EP testing. Although this testing
      was not required, it was performed in >50% of patients. Information regarding the
      results of EP testing was correlated to baseline clinical characteristics and
      outcome. RESULTS: Of 572 patients subjected to an EP test, 384 (67%) had
      inducible sustained VT or VF. Inducible patients were more likely to have
      coronary artery disease, previous infarction, and VT as their index arrhythmic
      event. Inducibility of VT or VF did not predict death or recurrent VT or VF.
      CONCLUSIONS: Information derived from EP testing in this patient population,
      particularly those with VF, is of limited value and may not be worth the risks
      and costs of the procedure, particularly in those patients likely to receive an
      ICD.

PMID- 12228786
TI  - Association of the human minK gene 38G allele with atrial fibrillation: evidence
      of possible genetic control on the pathogenesis of atrial fibrillation.
AB  - BACKGROUND: Human minK protein is the beta-subunit of I(Ks) potassium channel and
      plays an important role in cardiac cellular electrophysiology. We investigated
      the association between human atrial fibrillation and the polymorphism of minK
      gene (38G or 38S) with a case-control study. METHODS: We included 108 patients
      with atrial fibrillation and 108 control subjects. The case patients and control
      subjects were matched regarding age, sex, presence of valvular heart disease, and
      presence of left ventricular dysfunction. The genotype of minK was determined
      with polymerase chain reaction and restriction fragment analysis. RESULTS: The
      results showed an association between the minK 38G allele and atrial
      fibrillation. The odds ratios for atrial fibrillation in patients with 1 and 2
      minK 38G alleles were 2.16 (95% CI 0.81-5.74) and 3.58 (95% CI 1.38-9.27),
      respectively, when compared with patients without minK 38G allele. In a logistic
      regression model, the odds ratio for atrial fibrillation was 1.80 (95% CI 1.20
      2.71, P <.0046) for patients with 1 more minK 38G allele. CONCLUSION: We report
      the association between the minK 38G allele and clinical atrial fibrillation. Our
      findings suggest possible genetic control on the pathogenesis of atrial
      fibrillation.

PMID- 12228787
TI  - Greater pathogen burden but not elevated C-reactive protein increases the risk of
      clinical restenosis after percutaneous coronary intervention.
AB  - BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) constitutes
      a serious complication in the treatment of cardiovascular disease, but known risk
      factors do not fully account for the observed restenosis risk. Preliminary
      studies of infection or inflammation in restenosis report varied results. We
      tested whether C-reactive protein (CRP) or pathogen burden (seropositivity to 0,
      1, 2, or 3 pathogens, of Chlamydia pneumoniae [Cpn], cytomegalovirus [CMV], or
      Helicobacter pylori [Hpy]) predict clinical restenosis after percutaneous
      coronary intervention (PCI). METHODS: Blood samples were collected from 415
      patients undergoing PCI, and levels of plasma CRP and antibodies to Cpn, CMV, and
      Hpy were measured. The patient's medical history, demographics, and procedural
      data were recorded. Patient end points were determined for as long as 6 months as
      a means of evaluating the incidence of clinical restenosis and major adverse
      cardiac events. RESULTS: The average patient age was 62 years, and 80% of
      patients were male. Fifty-eight patients (14%) experienced clinical restenosis,
      whereas 17 patients (4%) died or had an acute myocardial infarction. After
      adjusting for 19 possible predictors, we found the pathogen burden (P-trend =.04,
      adjusted odds ratio [OR] 1.5 per number of pathogens) and minimum luminal
      diameter (P =.003, OR 1.8 per mm decrease) to be significant predictors of
      clinical restenosis. Male sex was a nonsignificant predictor of restenosis (P
      =.06, OR 2.2), but CRP was not significant after adjustment (P-trend =.10, OR
      0.73 per tertile). CONCLUSION: Pathogen burden was associated with clinical
      coronary restenosis, an association that deserves further exploration and
      evaluation. CRP, a marker of inflammation, was not associated with an increased
      risk of restenosis.

PMID- 12228788
TI  - Relationship between activated clotting time during percutaneous intervention and
      subsequent bleeding complications.
AB  - BACKGROUND: Approximately 50% of percutaneous coronary interventions in the
      United States are performed with unfractionated heparin and no IIb/IIIa agent.
      The operator must weigh the risks and benefits of more intensive anticoagulation
      during these percutaneous interventions. This study helps clarify the
      relationship between patient and procedural factors, such as the intensity of
      heparin anticoagulation as measured by activated clotting time (ACT), and the
      risk of blood loss and bleeding complications. METHODS: Four hundred twenty-nine
      patients undergoing elective or urgent percutaneous coronary intervention were
      followed up prospectively for 72 hours after intervention for clinical bleeding
      complications. Blood loss, defined as the difference between preprocedural and
      nadir postprocedural hematocrit adjusted for interval transfusions, was also
      tracked. In-laboratory ACTs, as well as other potential clinical and procedural
      predictors of blood loss and bleeding risk, were collected and analyzed. RESULTS:
      Maximum in-laboratory ACT was significantly related to blood loss as measured by
      the change in hematocrit (P =.017) and to the risk of major bleeding
      complications (P =.002). In multivariate analysis, patient age (P =.004), sex (P
      =.014), procedure length (P <.001), and additional interventions (P <.001) were
      significant, independent predictors of blood loss. Major bleeding complications
      were significantly, independently predicted by patient age (P <.001), additional
      interventions (P =.015), and maximum in-laboratory ACT (P <.001). CONCLUSIONS:
      Compared with the other clinical and procedural predictors of bleeding
      complications, maximum in-laboratory ACT was second only to patient age in
      significance as a multivariate predictor of postprocedural bleeding
      complications. Maximum in-laboratory ACT was found to be the most significant
      modifiable univariate and multivariate predictor of clinical bleeding
      complications after percutaneous coronary intervention. Particularly in patients
      with nonmodifiable risk factors for blood loss and bleeding complications such as
      advanced age, female sex, and multiple and prolonged procedures, avoiding high
      intensity anticoagulation with unfractionated heparin is associated with lower
      bleeding risk.

PMID- 12228789
TI  - Effects of sibutramine on ventricular dimensions and heart valves in obese
      patients during weight reduction.
AB  - BACKGROUND: Obesity enhances hemodynamic alterations that predispose to a
      subsequent increase in left ventricular (LV) wall stress leading to LV
      hypertrophy. In obese subjects, weight reduction regresses LV mass (LVM),
      regardless of blood pressure. Sibutramine can increase blood pressure and heart
      rate, which may attenuate the reductions in LVM associated with weight loss.
      METHODS: Outpatients (n = 184, age 18-65 y, body mass index > or =30 to <40
      kg/m2) were randomly assigned to 6 months of once daily double-blind treatment
      with sibutramine 10 mg or 20 mg, or placebo. LV dimensions, status and function
      of the valves, weight loss, blood pressure, heart rate, and electrocardiogram
      were assessed. RESULTS: For end point data sets, the mean +/- SD LVM index
      (LVM/height) changes were -3.0 +/- 11.9 g/m for placebo (n = 56), -4.4 +/- 10.7
      g/m for sibutramine 10 mg (n = 61), and -4.3 +/- 10.9 g/m for sibutramine 20 mg
      (n = 56). The reductions observed in the sibutramine groups were statistically
      significant compared with baseline (P <.01), but pairwise comparison results with
      placebo were not statistically significant. There was no difference in overall
      status of the cardiac valves. A statistically significant greater weight loss was
      found in patients on both doses of sibutramine compared with placebo (P <.001).
      No statistically significant differences between the groups were observed in
      respect to blood pressure and electrocardiographic intervals, but a statistically
      significant increase in pulse rate (7 beats/min) was noted for patients with
      sibutramine treatment. CONCLUSION: A 6-month treatment with sibutramine does not
      affect ventricular dimensions, heart valves, and electrocardiogram variables.

PMID- 12228790
TI  - Determinants of tissue Doppler measures of regional diastolic function during
      dobutamine stress echocardiography.
AB  - BACKGROUND: Diastolic dysfunction induced by ischemia may alter transmitral blood
      flow, but this reflects global ventricular function, and pseudonormalization may
      occur with increased preload. Tissue Doppler may assess regional diastolic
      function and is relatively load-independent, but limited data exist regarding its
      application to stress testing. We sought to examine the stress response of
      regional diastolic parameters to dobutamine echocardiography (DbE). METHODS:
      Sixty-three patients underwent study with DbE: 20 with low probability of
      coronary artery disease (CAD) and 43 with CAD who underwent angiography. A
      standard DbE protocol was used, and segments were categorized as ischemic, scar,
      or normal. Color tissue Doppler was acquired at baseline and peak stress, and
      waveforms in the basal and mid segments were used to measure early filling (Em),
      late filling (Am), and E deceleration time. Significant CAD was defined by
      stenoses >50% vessel diameter. RESULTS: Diastolic parameters had limited
      feasibility because of merging of Em and Am waves at high heart rates and limited
      reproducibility. Nonetheless, compared with normal segments, segments subtended
      with significant stenoses showed a lower Em velocity at rest (6.2 +/- 2.6 cm/s vs
      4.8 +/- 2.2 cm/s, P <.0001) and peak (7.5 +/- 4.2 cm/s vs 5.1 +/- 3.6 cm/s, P
      <.0001). Abnormal segments also showed a shorter E deceleration time (51 +/- 27
      ms vs 41 +/- 27 ms, P =.0001) at base and peak. No changes were documented in Am.
      The same pattern was seen with segments identified as ischemic with wall motion
      score. However, in the absence of ischemia, segments of patients with left
      ventricular hypertrophy showed a lower Em velocity, with blunted Em responses to
      stress. CONCLUSION: Regional diastolic function is sensitive to ischemia.
      However, a number of practical limitations limit the applicability of diastolic
      parameters for the quantification of stress echocardiography.

PMID- 12228791
TI  - Prognostic significance of mitral regurgitation and tricuspid regurgitation in
      patients with left ventricular systolic dysfunction.
AB  - BACKGROUND: Mitral regurgitation (MR) and tricuspid regurgitation (TR) frequently
      develop in patients with left ventricular systolic dysfunction (LVSD).
      Ventricular volume overload that occurs in patients with MR and TR may lead to
      progression of myocardial dysfunction. We hypothesized that MR and TR would
      provide markers of risk in patients with LVSD. METHODS: We reviewed clinical,
      electrocardiographic, and echocardiographic data on 1421 consecutive patients
      with LVSD (left ventricular ejection fraction < or =35%). Predictors of survival
      (freedom from death or United Network for Organ Sharing [UNOS]-1 transplantation)
      were identified in a multivariable analysis with a Cox proportional hazards
      analysis. The impact of MR and TR (none to mild, moderate, or severe) then was
      assessed separately with Kaplan-Meier survival analysis. RESULTS: During the
      follow-up period (mean +/- SD, 365 +/-364 days), death occurred in 435 study
      subjects (31%) and UNOS-1 transplantation in 28 subjects (2%). Multivariable
      predictors of poor outcome included increasing MR and TR grade, cancer, coronary
      artery disease, and absence of an implantable cardiac defibrillator. Relative
      risk was 1.84 (95% CI 1.43-2.38) for severe MR and 1.55 (95% CI 1.14-2.11) for
      severe TR. Survival with Kaplan-Meier analysis related inversely to MR grade
      (none to mild 1004 +/-31 days, moderate 795 +/-34 days, severe 628 +/-47 days, P
      <.0001) and TR grade (none to mild 977 +/-28 days, moderate 737 +/-40 days,
      severe 658 +/-55 days, P =.0001). CONCLUSION: Patients with severe MR or TR
      represent high-risk subsets of patients with LVSD. Future study is warranted to
      determine whether pharmaceutical or surgical strategies to relieve MR and TR have
      a favorable impact on survival.

PMID- 12228792
TI  - Is cardiovascular remodeling in patients with essential hypertension related to
      more than high blood pressure? A LIFE substudy. Losartan Intervention For
      Endpoint-Reduction in Hypertension.
AB  - BACKGROUND: Blocking the renin-aldosterone-angiotensin II system has been
      hypothesized to induce blood pressure-dependent as well as blood pressure
      independent regression of cardiovascular hypertrophy. However, the relative
      influence of elevated blood pressure (BP) and various neurohormonal factors on
      cardiovascular remodeling in hypertension is unclear. METHODS: In 43 untreated
      patients with hypertension with electrocardiographic left ventricular
      hypertrophy, we measured relative wall thickness and left ventricular mass index
      by echocardiography and by magnetic resonance imaging (n = 32), intima-media
      cross-sectional area, and distensibility of the common carotid arteries by
      ultrasound, media/lumen ratio of isolated subcutaneous resistance arteries by
      myography, and median 24-hour systolic BP (n = 40), serum insulin, and plasma
      levels of epinephrine, norepinephrine, renin, angiotensin II, aldosterone, and
      endothelin. RESULTS: In multiple regression analyses, left ventricular mass index
      by echocardiography (R2 = 0.14, P <.05) and by magnetic resonance imaging (R2 =
      0.32, P =.001) were associated with 24-hour systolic BP, whereas relative wall
      thickness was associated with plasma epinephrine (R2 = 0.12, P <.05) and
      aldosterone (R2 = 0.10, P <.05). Intima-media cross-sectional area/height was
      associated with 24-hour systolic BP (beta = 0.40) and plasma epinephrine (beta =
      0.43) (adjusted R2 = 0.32, P <.001), whereas carotid distensibility was
      associated with 24-hour systolic BP (beta = 0.40) and plasma angiotensin II (beta
      = -0.41) (adjusted R2 = 0.30, P <.001). Media/lumen ratio in subcutaneous
      resistance arteries was associated with plasma epinephrine (R2 = 0.22, P <.01).
      CONCLUSION: Apart from being associated with a high BP burden, cardiovascular
      remodeling was associated with high levels of circulating epinephrine,
      aldosterone, as well as angiotensin II, suggesting a beneficial effect above and
      beyond the effect of BP reduction when using antihypertensive agents blocking the
      receptors of these neurohormonal factors.

PMID- 12228793
TI  - Impact of disease activity on left ventricular performance in patients with
      acromegaly.
AB  - BACKGROUND: In patients with acromegaly, abnormalities of systolic and diastolic
      left ventricular (LV) performance, mostly associated with hypertension or LV
      hypertrophy, have been reported. We used 2-dimensional/Doppler echocardiographic
      methods and tissue Doppler imaging (TDI) to elucidate the impact of disease
      activity on LV function in patients with acromegaly. METHODS: In a prospective
      study design, 15 patients with active acromegaly (AA group; mean age-adjusted
      serum insuline-like growth factor-I [IGF-I] level, 420 +/- 170 ng/mL, mean growth
      hormone nadir during 75-g oral glucose load, 12.3 +/- 30.1 microg/L), 18 patients
      with cured (n = 14, mean IGF-I level 205 +/- 115 ng/mL, mean growth hormone nadir
      during glucose load 0.72 +/- 0.34 microg/L) or well-controlled (n = 4, normal age
      adjusted ranges of IGF-I levels with medication with somatostatin analogues 354
      +/- 88 ng/mL) acromegaly (CA group), and 24 control subjects (control group)
      underwent 2-dimensional/Doppler echocardiographic measurements, including
      assessment of the Tei index (isovolumic contraction time and isovolumic
      relaxation time divided by ejection time). Systolic and diastolic mitral annular
      velocities (peak systolic velocity, peak early diastolic velocity [E'], peak late
      diastolic velocity [A'], E'/A' ratio) were derived from pulsed TDI. RESULTS: No
      significant differences between study groups were observed with respect to muscle
      mass and systolic parameters, such as ejection fraction, fractional shortening,
      and peak systolic velocity. In patients with AA, E' and the E'/A' ratio were
      lower than in control and CA subjects (AA 6.8 +/- 1.7 cm/s, control 10.0 +/- 1.7
      cm/s, CA 9.1+/- 3.0 cm/s, P <.01 AA vs control, P <.05 AA versus CA, AA 0.68 +/-
      0.22, control 0.98 +/- 0.16, CA 0.89 +/- 0.37, P <.01 AA vs control and CA,
      respectively). In comparison with control subjects and patients with CA, patients
      with AA had a reduced mitral peak velocity of early/late filling ratio (AA 0.78
      +/- 0.22 m/s, control 1.12 +/- 0.33 m/s, CA 1.11 +/- 0.36 m/s, P <.05 AA vs
      control and CA) and a prolonged deceleration time (AA 223 +/- 41 ms, control 188
      +/- 26 ms, CA 185 +/- 25 ms, P <.05 AA vs control and CA). The Tei index was
      significantly elevated in patients with AA in comparison with control subjects
      and patients with CA (AA 0.54 +/- 0.13, control 0.40 +/- 0.09, CA 0.44 +/- 0.10,
      P <.05 AA vs control and CA). No significant differences were observed between
      control subjects and patients with CA with respect to mitral flow-derived
      variables, TDI parameters, and the Tei index. CONCLUSION: Disease activity has a
      significant impact on LV performance in patients with acromegaly. In subjects
      with active disease, diastolic dysfunction and beginning impairment of overall LV
      performance are present. In patients with cured/well-controlled disease, systolic
      and diastolic function appear normal.

PMID- 12228794
TI  - Emergency endovascular interventions for ruptured thoracic and abdominal aortic
      aneurysms.
AB  - BACKGROUND: The purpose of our study was to show the effectiveness of
      endovascular stent grafts in the treatment of acutely ruptured abdominal and
      thoracic aortic aneurysms as an alternative to the conventional surgical approach
      in an emergency setting. METHODS: From October 1996 to October 1998 we deployed 9
      emergent endovascular stent grafts--6 in the abdominal aorta and 3 in the
      thoracic aorta. Aortic rupture was confirmed before surgery with spiral-computed
      tomographic scan. The average interval from onset of symptoms to treatment was
      4.5 hours. We used commercially manufactured stent grafts: 4 Corvita (Corvita
      Inc/Schneider Corp/Boston Scientific Corp, Natick, Mass), 3 Talent (World Medical
      Inc, Surise, Fla/Medtronic, Sunnyvale, Calif), and 2 Vanguard (Boston Scientific
      Corp, Natick, Mass). RESULTS: Deployment of the stent grafts was successful in
      all cases. Two patients died in the follow-up period (120 months) from myocardial
      infarction. No cases were seen of paraplegia or stent migration. However, 2
      endoleaks, 1 in-stent stenosis, 1 temporary renal failure, and 1 brief episode of
      myocardial ischemia occurred. CONCLUSION: Our experiences with emergency
      endovascular stent grafting show that the procedure is technically feasible, with
      less morbidity and mortality than conventional open surgery, in selected
      patients.

PMID- 12228796
TI  - Trans-Atlantic hospital agreement in reading first day radiographs of clinically
      suspected scaphoid fractures.
AB  - The purpose of this study was to describe the agreement between two hospitals on
      either side of the Atlantic Ocean in reading first day plain radiographs of
      suspected scaphoid fractures. Two groups of observers, one North American and one
      European, consisting of observers at various levels of training were compared.
      Kappa statistics were used to determine inter- and intra-observer agreement. The
      receiver-operating characteristics (ROC) curves and area under this curve (AUC)
      for each observer were calculated to determine test performance. Scaphoid
      radiographs of 80 consecutive patients seen with clinically suspected scaphoid
      fracture were included in the study. The results of the bone scan were used as
      the reference standard. There is an acceptable agreement between the USA and
      Europe for both radiologists and orthopaedic surgeons at various levels of
      training (kappa 0.45-0.88). Intra-observer agreement is acceptable as well (kappa
      0.46-0.86). Considering all normal or equivocal radiographs, there is slight to
      moderate agreement at all levels of training in and between both centres and
      specialities (kappa 0-0.64). Overall test performance was acceptable for all
      consecutive radiographs (AUC 0.65-0.82) and poor for the normal radiographs (AUC
      0.46-0.65). We could not detect differences in performance due to location of the
      readers' hospital or institution of training. The use of more sensitive
      techniques should be restricted to patients with negative or equivocal
      radiographs in clinically suspected scaphoid fractures.

PMID- 12228797
TI  - The use of external fixators in the immobilization of pediatric fractures.
AB  - The use of external fixation in the immobilization of diaphyseal and metaphyseal
      fractures in children is still controversial, as these fractures are generally
      managed by immediate plaster casting, by traction followed by casting, by various
      methods of internal fixation, including the recently developed flexible rods, and
      by plating. Between 1982 and 1998, we treated 64 children with fractures of the
      long bones of the lower limb using external fixation, 44 of whom were available
      for follow-up (46 fractures). Their average age on the day of injury was 8.l
      years. Average follow-up extended for 4 years. The external fixation used was
      left in place for an average of 67 days. Full range of movement was achieved in
      42 children (44 limbs). The longitudinal axis was anatomically correct (<5
      degrees angulation) in 40 children (42 limbs). Due to malalignment of the
      fracture (15 degrees varus) in one child, tibial osteotomy was performed 4 years
      after fracture healing. There was no leg length discrepancy in 38 children, and
      shortening of >2 cm was measured in the fractured limbs of 2 children. We found
      the use of external fixators to be easy, quick, with a short learning curve, and
      appropriate for comminuted and closed fractures of the long bones, and especially
      for children with polytrauma.

PMID- 12228798
TI  - Prognostic significance of the Nasca classification for the long-term course of
      congenital scoliosis.
AB  - AIM: The aim of our investigations was to answer the question of whether the
      radiologic classification according to the investigations of Nasca has prognostic
      relevance for congenital scoliosis. Based on our results, a therapeutic concept
      was given. PATIENTS AND METHODS: Radiographs of 49 patients with a congenital
      scoliosis were classified according to Nasca. The progression of the malformation
      was analyzed by regarding the changes over a period of 8.3 years on average.
      RESULTS: Of the analyzed patients with congenital scoliosis, 73% showed a mean
      progression rate of 1.8 degrees per year. The most advanced progress of the Cobb
      angle per year was seen in patients with unilateral unsegmented bars with or
      without additional hemivertebrae (type 4 according to the Nasca classification)
      and patients with wedge-formed vertebrae (type 2a according to the Nasca
      classification). The presence of unilateral bars and the location of the
      hemivertebra or hemivertebrae (type 4) and wedge-formed vertebrae (type 2a) are
      the major determinants of deformity. Within the scope of our investigations, the
      following three factors were seen as deleterious when combined: thoracolumbal and
      long-distance scoliosis, female gender, and prepubertal growth period.
      CONCLUSION: From our analysis of 49 patients, we can propose the following
      therapeutic system for congenital scoliosis. Sole treatment with physiotherapy
      should only be recommended with congenital scoliosis curves ranging from 0
      degrees to 20 degrees according to the Cobb method. With a Cobb angle smaller
      than 40 degrees and some flexibility remaining in the spine, the congenital
      scoliosis should be treated additionally with corrective casts. For congenital
      scoliosis with a Cobb angle of more than 50 degrees, as well as for congenital
      scoliosis with a poor prognosis (for example unilateral bars), a spondylodesis of
      the spine should be done before reaching the age of 5 years.

PMID- 12228799
TI  - Functional treatment of the distal third humeral shaft fractures.
AB  - OBJECTIVE: The objective of the present study was to determine the effectiveness
      of functional treatment for distal third humeral shaft fractures in young adults.
      PATIENTS AND METHODS: A custom-made prefabricated brace was applied for the
      functional treatment of 21 isolated, closed, distal third humeral shaft fractures
      of 21 patients (17 male and 4 female). Their average age was 25 years (range 18
      37 years). The mean follow-up period was 39 weeks. RESULTS: All of the fractures
      united. The average time to union was 12 weeks. The average varus angulation was
      7.8 deg in 8 patients, and the average shortening of the fractured limb was 10 mm
      in 4 patients. Minimal motion restrictions mostly occurred in shoulder abduction
      and lateral rotation. No patient showed a lack of elbow motion. Angulatory
      deformities and shortening had no effect on the functional outcome. None of the
      patients suffered radial nerve palsy during the course of treatment or due to
      entrapment in the callus of the healed fracture. CONCLUSIONS: Young adults who
      have isolated, closed, distal third humeral shaft fractures are good candidates
      for functional bracing.

PMID- 12228800
TI  - The use of amniotic membrane in flexor tendon repair: an experimental model.
AB  - BACKGROUND: The objective of this study was to investigate the use of amniotic
      membrane as a long-term bioprosthesis in hand surgery. The role of the amniotic
      membrane was investigated in chickens with regard to the prevention of adhesion
      formation following tendon repair in zone II. METHODS: In the control group, the
      flexor tendon sheath was excised and the tendon repaired. In group II, both the
      flexor digitorum profundus tendon and its sheath were repaired. In group III, the
      repaired tendon was covered with amniotic membrane. Histological evaluation of
      the repaired tendons were done at 3, 6 and 12 weeks. RESULTS: Results of
      histologic examination demonstrated that use of the amniotic membrane
      significantly reduced the amount of adhesion compared with the other groups.
      Three months after implantation no remnants of amniotic membrane could be
      identified at the tendon repair site. CONCLUSIONS: Amniotic membrane is easily
      prepared, and because of its cost effectiveness, its use in the prevention and
      treatment of adhesions should always be kept in mind.

PMID- 12228801
TI  - An expandable nailing system for the management of pathological humerus
      fractures.
AB  - BACKGROUND: People with metastatic fracture of the humerus are of poor general
      health. Often they are not able to compensate the handicap of an impaired
      extremity. Standard osteosynthetic techniques are not always applicable. To
      reduce the trauma of the operation, we used the Fixion expandable nail system.
      METHODS: At two centers, 23 metastatic fractures of the humerus (in 22 patients)
      were stabilized with a new nailing system. The nail expands under hydraulic
      pressure up to 150% of its uninflated diameter, gaining long frictional contact
      to the bone. All patients were followed up until osseous healing occurred or
      until they died. RESULTS AND CONCLUSIONS: The operative time was approximately 32
      min, including 1.4 min fluoroscopy time. Nail insertion is brief and therefore
      not very stressful to the group of debilitated patients who require this
      intervention. Immediately postoperatively, the upper extremity is stable to
      permit physiotherapy. In these few patients, we saw no complications. The
      advantages of the surgical approach appear to outweigh those of conservative
      management options if a simple and safe surgical technique makes the humerus
      stable enough to resist normal daily loads.

PMID- 12228802
TI  - Measurement of the humeral head retroversion angle. A new radiographic method.
AB  - BACKGROUND: In this study, a simple and reliable radiographic method is described
      to determine the torsional profile of the humeral head. METHODS: First, by using
      a specially developed frame, the humeral head retroversion angles (HRAs) of 20
      dry humeri were measured by an anatomist and an orthopedist. Then the HRA of
      these humeri were measured by two orthopedists on radiographs taken in semi-axial
      view when the humeri were in 20 degrees abduction. RESULTS: The results were
      assessed with the SPSS 9.05 program, and the repeatability coefficient of both
      methods was 98%. The average difference in angle determination between the two
      methods was 0.9 degrees; the maximum difference was 3 degrees. After that,
      posteroanterior semi-axial radiographs of both humerus bones of 40 healthy
      volunteers were taken by positioning their arms in 20 degrees abduction to the X
      ray axis. The mean HRA difference between the right and left sides was 0.4
      degrees (maximum difference 3 degrees ) and is of no clinical significance. It
      was determined that left and right HRAs can be taken as a reference to each
      other. For measurement of the HRA in the planning of proximal humeral rotation
      osteotomy and prosthesis replacement arthroplasty, the presented radiographic
      method can be used with a high rate of accuracy.

PMID- 12228803
TI  - Supplementary transverse wire fixation through cuneiforms and cuboid in
      combination with a screw for the comminuted tarsal navicular fractures.
AB  - An isolated fracture dislocation of the body of the tarsal navicular is an
      unusual injury; a displaced one is difficult to treat, and a comminuted one poses
      a further therapeutic problem. Previously, several authors have described various
      options with additional fixation across the cuneonavicular joint through a tarsal
      navicular. However, in the comminuted tarsal navicular fracture, the question
      arises regarding the efficacy of the wires through the comminuted fracture
      fragments to maintain satisfactory reduction. The technique that several authors
      have described is impractical for the treatment of a severe comminuted tarsal
      navicular fracture. We present two cases of a comminuted fracture treated with
      open reduction and internal fixation with supplementary wire fixation through
      cuneiforms and cuboid as an ancillary method. This method proved to be
      satisfactory for the treatment of a comminuted fracture of the body of the
      navicular.

PMID- 12228804
TI  - Ossification of Achilles tendon--report of three cases.
AB  - BACKGROUND: Ossification of the Achilles tendon is reportedly an unusual
      condition. The microscopic features of such ossifications have been not well
      documented. METHODS: We treated three patients with bilateral ossification of the
      Achilles tendon and examined the specimens microscopically. The patients were all
      male. Their ages ranged from 41 to 59 years with an average of 48 years. The
      chief complaint was pain in two cases and rupture of the Achilles tendon in one
      case. The ossification site was near the insertion in five feet and in the tendon
      body in one foot. They had no laboratory abnormalities. RESULTS: Removal was
      performed in two cases. Microscopic examination revealed no active inflammation
      of the ossified tendon. Lamellar bone formation with bone marrow continuous with
      the extensive cartilage metaplasia, namely enchondral ossification, and osteoid
      formation in the granulation tissue, namely intramembranous ossification, were
      observed. CONCLUSIONS: Judging from the heavy work and bilateral occurrence in
      the present cases, repetitive microtrauma to the Achilles tendon and some
      predisposition are implicated as causative factors in the ossification.

PMID- 12228805
TI  - Treatment of congenital scoliosis in an 8-month-old child.
AB  - Congenital scoliosis due to fully segmented hemivertebrae is most often
      progressive and requires treatment. Currently, the operative treatment
      recommended includes (a) posterior spinal fusion with or without instrumentation
      and (b) anterior and posterior exposure with fusion, epiphysiodesis or
      hemivertebral excision. We report the case of a patient who was operated on at
      the age of 8 months by a single-stage posterior approach with a transpedicular
      hemivertebral resection and convex hemepiphysiodesis combined with a low-profile
      posterior unilateral instrumentation. The goals were the prevention of
      progression, potential correction by growth on the concave side, short hospital
      stay, reduction in the morbidity associated with a separate anterior approach,
      and no need for postoperative bracing. Preliminary results after a follow-up
      period of 2 years support the impression that this approach bears significant
      advantages compared to previously preferred anteroposterior procedures.

PMID- 12228806
TI  - The genetic complexity of chitin synthesis in fungi.
AB  - Chitin synthesis is a process maintained across the fungal kingdom that, thanks
      to the power of genetic manipulation of yeast cells, is now beginning to be
      understood. Chitin synthesis is based on the regulation of distinct chitin
      synthase isoenzymes whose number ranges from one in Schizosaccharomyces pombe to
      seven in some filamentous fungi, such as Aspergillus fumigatus. This high
      diversity makes it difficult to find a unique model of regulation. However, the
      results available suggest common themes in regulation. The arrival of the genomic
      era, together with the development of fungal genetic technology should allow
      experimental approaches to this process.

PMID- 12228807
TI  - Suppression of Saccharomyces cerevisiae rad27 null mutant phenotypes by the 5'
      nuclease domain of Escherichia coli DNA polymerase I.
AB  - RNA primer removal from Okazaki fragments during lagging-strand replication and
      the excision of damaged DNA bases requires the action of structure-specific
      nucleases, such as the mammalian flap endonuclease 1 (FEN-1). This nuclease
      contains two conserved motifs enriched with acidic amino acid residues that are
      important for catalytic function. Similar motifs have been identified in
      nucleases found in viruses, archebacteria, eubacteria, and in eukaryotes ranging
      from yeast to humans. Unique among these proteins, the putative FEN-1 homologue
      in Escherichia coli is contained within the N-terminal region of the DNA
      polymerase I (PolN). To demonstrate that the cellular functions of FEN-1 reside
      in PolN, we cloned and expressed the amino terminal domain (323 amino acid
      residues) of PolI in a Saccharomyces cerevisiae strain lacking the FEN-1
      homologue RAD27. Overexpression of PolN suppressed, to varying degrees,
      phenotypes associated with a rad27 null strain. These include temperature
      sensitivity, Okazaki fragment processing, a mutator phenotype, a G2/M cell cycle
      arrest, minichromosome loss, and methyl methane sulfonate sensitivity. We
      purified Rad27 and PolN proteins in order to determine whether differences in
      their intrinsic nuclease activities or interaction with proliferating cell
      nuclear antigen (PCNA) could explain the partial suppression of some phenotypes.
      We found that the in vitro nuclease activities of Rad27 were more potent than
      those of PolN and the activity of Rad27, but not PolN, was stimulated by PCNA. We
      conclude that the N-terminal nuclease domain of E. coli polymerase I encodes a
      functional homologue of FEN-1.

PMID- 12228809
TI  - Old yellow enzyme confers resistance of Hansenula polymorpha towards allyl
      alcohol.
AB  - In the methylotrophic yeast, Hansenula polymorpha, peroxisomes are formed during
      growth on methanol as sole carbon and energy source and contain the key enzymes
      for its metabolism, one of the major enzymes being alcohol oxidase (AO). Upon a
      shift of these cells to glucose-containing medium, peroxisomes become redundant
      for growth and are rapidly degraded via a highly selective process designated
      macropexophagy. H. polymorpha pdd mutants are disturbed in macropexophagy and
      hence retain high levels of peroxisomal AO activity upon induction of this
      process. To enable efficient isolation of PDD genes via functional
      complementation, we make use of the fact that AO can convert allyl alcohol into
      the highly toxic compound acrolein. When allyl alcohol is added to cells under
      conditions that induce macropexophagy, pdd mutants die, whereas complemented pdd
      mutants and wild-type cells survive. Besides isolating bona fide PDD genes, we
      occasionally obtained pdd transformants that retained high levels of AO activity
      although their allyl alcohol sensitive phenotype was suppressed. These invariably
      contained extra copies of a gene cluster encoding homologues of Saccharomyces
      carlsbergensis old yellow enzyme. Our data suggest that the proteins encoded by
      these genes detoxify acrolein by converting it into less harmful components.

PMID- 12228811
TI  - Nuclear small subunit rRNA group I intron variation among Beauveria spp provide
      tools for strain identification and evidence of horizontal transfer.
AB  - An optional group I intron was characterized at a single insertion point in
      nuclear small subunit rRNA (nuSSU rRNA) genes of the imperfect entomopathogenic
      fungi, Beauveria bassiana and B. brongniartii. Insertion points were conserved
      among nuSSU rRNA genes from 35 Beauveria isolates. PCR-RFLP and DNA sequencing
      identified 12 group I intron variants and were applied to the identification of
      strains isolated from insect hosts. Alignment of 383-404-nt subgroup IB3 group I
      introns indicated that four insertion/deletion (indel) mutations were the main
      basis of fragment length variation. Phylogeny reconstruction using parsimony and
      neighbor-joining methods suggested six lineages may be present among nuSSU rRNA
      group I intron sequences from Beauveria and related ascomycete fungi. Terminal
      node placement of Beauveria introns conflicted with previously published
      phylogenies constructed from gene sequences, suggesting horizontal transfer of
      group I introns. PCR-RFLP among introns provided a means for the differentiation
      of Beauveria isolates.

PMID- 12228808
TI  - Role of SGS1 and SLX4 in maintaining rDNA structure in Saccharomyces cerevisiae.
AB  - To address the role of SGS1 in controlling genome stability we previously
      identified several slx mutants that require SGS1 for viability. Here, we report
      the isolation and characterization of temperature-sensitive (ts) SGS1 alleles in
      cells lacking SLX4. At the non-permissive temperature (37 degrees C) sgs1-ts slx4
      cells progress through S-phase and arrest growth as large-budded cells with at
      least a 2C DNA content. Analysis of the integrity of the replicated DNA by pulsed
      field gel electrophoresis revealed that chromosome XII (ChrXII) was uniquely
      altered, as it was unable to enter the gel. This defect was specific to the
      tandem rDNA repeats on ChrXII and occurred as cells progressed through S-phase at
      37 degrees C. Reciprocal-shift experiments revealed that viability and ChrXII
      migration can be restored by allowing Sgs1 to act between G2/M and the subsequent
      G1 phase. These results suggest that Sgs1 and Slx4 are not required for bulk DNA
      synthesis but play redundant roles in maintaining rDNA structure during DNA
      replication.

PMID- 12228810
TI  - Targeted disruption of a G protein alpha subunit gene results in reduced
      pathogenicity in Fusarium oxysporum.
AB  - The cloning of fga1, the gene encoding a G protein alpha subunit, was performed
      by standard PCR techniques and by screening a Fusarium oxysporum genomic library,
      using the PCR product as a probe. The full-length open reading frame spanned
      1,059 nucleotides and the deduced primary structure of the protein (353 amino
      acid residues) showed high identity to those of G protein alpha(i) family
      proteins from other filamentous fungi. Disruption of fga1 had no effect on
      vegetative growth, but reduced the conidiation and pathogenicity of the fungus.
      Disruptants also showed a decreased level of intracellular cAMP and increased
      resistance to heat shock at 45 degrees C. These results suggest that the Galpha
      subunit encoded by fga1 is involved in a signal transduction pathway in F.
      oxysporum that controls conidiation, heat resistance and pathogenicity.

PMID- 12228812
TI  - Disruption of the Aspergillus niger argB gene: a tool for transformation.
AB  - We disrupted the Aspergillus niger gene argB, encoding ornithine
      transcarbamylase. Full characterisation of the argB deletion was performed by
      Southern blot analysis, growth tests and by means of mitotic recombination,
      complementation and transformation. The argB locus was found to be physically
      removed, thus creating an auxotrophic mutation. The latter can be supplemented by
      addition of arginine into the culture medium. The argB gene and its disruption do
      not correlate to the argI13 (formerly argB13) allele described. The delta argB is
      on chromosome I whereas argI13 is on V. In addition, the argI13 mutation can only
      be complemented by the A. nidulans argB gene, whereas the new argB deletion can
      be complemented by both the A. niger and A. nidulans argB genes. The delta argB
      strain has been used to generate several strains in a breeding programme and to
      study the expression of important genes, such as areA and kexB.

PMID- 12228813
TI  - Lack of behavior change after disclosure of hepatitis C virus infection among
      young injection drug users in Baltimore, Maryland.
AB  - We evaluated behavior change after disclosure of a positive hepatitis C virus
      (HCV) antibody test result among a cohort of young injection drug users (IDUs).
      Participants underwent semiannual interviews, human immunodeficiency virus (HIV)
      and HCV antibody testing, and pretest and posttest counseling. We used chi(2)
      statistics to study changes in the frequencies of high-risk behaviors from
      baseline to a 6-month follow-up visit among 46 IDUs who had a positive HCV test
      result and among 60 IDUs who did not have a positive HCV test result or who were
      unaware of their test result. No significant differences were detected between
      the 2 groups. Both groups continued to share syringes, needles, and other
      injection paraphernalia. These findings suggest that young IDUs may not be aware
      of the risk of HCV infection and highlight the urgent need for post-HCV test
      guidelines and behavioral interventions to reduce ongoing high-risk behavior that
      perpetuates the risk of HCV transmission.

PMID- 12228814
TI  - Insights into SEN virus prevalence, transmission, and treatment in community
      based persons and patients with liver disease referred to a liver disease unit.
AB  - To document the prevalence and routes of transmission of SEN virus (SEN-V) in
      community-based individuals and patients referred to a liver disease unit, stored
      serum samples obtained from 160 Canadian Inuit and 140 patients with liver
      disease were tested for SEN-V DNA by polymerase chain reaction. In the community
      based population, SEN-V was present in 57 (36%) of 160 persons. SEN-V-positive
      individuals tended to be younger and were more often male. Liver enzyme levels
      and serologic markers for hepatitis A and B viruses were similar in SEN-V
      positive and SEN-V-negative individuals. SEN-V was present in 30 (21%) of the 140
      patients with liver disease. Age, sex, risk factors for viral acquisition,
      prevalence of symptoms, and liver biochemical and histological findings were
      similar in SEN-V-positive and SEN-V-negative patients. These results indicate
      that SEN-V infection is a common viral infection in both healthy individuals and
      patients with chronic liver disease, that transmission likely occurs via
      nonparenteral routes, and that SEN-V infection is not associated with higher
      rates of or more-severe liver disease in persons with preexisting liver disease.

PMID- 12228815
TI  - Risk of tuberculin skin test conversion among health care workers: occupational
      versus community exposure and infection.
AB  - A prospective observational cohort study to assess rates of and risk factors for
      tuberculin skin test (TST) conversion among health care workers (HCWs) was
      conducted at an urban hospital located in a high tuberculosis-incidence area in
      1994-1998. All hospital employees undergoing required testing every 6 months were
      included. A total of 69 (1.2%) of 5773 susceptible employees had a documented TST
      conversion (overall rate, 0.38 per 100 person-years worked). No significant
      difference existed in conversion rates among employees with frequent, limited, or
      no patient contact. HCWs with a TST conversion lived in zip codes with higher
      tuberculosis case rates (P< or =.05). In multivariate analysis, TST conversion
      was associated with history of bacille Calmette-Guerin vaccination (relative risk
      [RR], 11.63), annual salary <$20,000 (RR, 3.67), and increasing age. In the
      setting of an effective tuberculosis infection-control program, TST conversion
      rates were low, and risk of conversion among HCWs was associated most strongly
      with nonoccupational factors.

PMID- 12228816
TI  - Mycobacterium simiae pseudo-outbreak resulting from a contaminated hospital water
      supply in Houston, Texas.
AB  - Various species of nontuberculous mycobacteria are known to cause nosocomial
      pseudo-outbreaks, but there have been no detailed reports of nosocomial
      Mycobacterium simiae pseudo-outbreaks. From April 1997 through February 2001, we
      recovered 65 M. simiae isolates from 62 patients at a community teaching hospital
      in Houston, Texas. The organism was grown in various water samples obtained in
      the hospital building and in professional building 1 but not in professional
      building 2, which has a separate water supply system. Thirty-one environmental
      and human outbreak-related M. simiae isolates had indistinguishable or closely
      related patterns on pulsed-field gel electrophoresis and were considered clonal.
      M. simiae can be a cause of nosocomial pseudo-outbreaks. The reservoir for this
      pseudo-outbreak was identified as a contaminated hospital water supply.

PMID- 12228817
TI  - Large epidemic of adenovirus type 4 infection among military trainees:
      epidemiological, clinical, and laboratory studies.
AB  - Outbreaks of adenovirus type 4 (Ad4) acute respiratory disease (ARD) have
      reemerged among US military personnel during the past decade. A prospective
      epidemiological investigation of 678 military recruits was conducted at Fort
      Jackson, South Carolina, in the fall of 1998; 115 (17%) of the recruits were
      hospitalized for febrile ARD. Adenovirus types 4, 3, and 21 were recovered from
      the cultures of 70 (72%), 7 (7%), and 2 (2%) of 97 recruits, respectively. In
      addition, 69 (83%) of the 83 hospitalized and 82 (49%) of the 166 nonhospitalized
      unit contacts had seroconversion to Ad4, which indicates the very high
      susceptibility and communicability of Ad4 among military recruits. Young age (<20
      years) and male sex increased the risk for anti-Ad4 seroconversion. Recruits from
      tropical areas had higher preexisting immunity than did recruits from temperate
      regions. Military recruits are highly susceptible to Ad4 infections. Prompt
      reinstitution of an adenovirus vaccination program in this high-risk population
      is urgently needed.

PMID- 12228818
TI  - Community-acquired methicillin-resistant Staphylococcus aureus infections in
      France: emergence of a single clone that produces Panton-Valentine leukocidin.
AB  - To characterize the clinical and bacteriologic characteristics of community
      acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, we
      reviewed 14 cases that were diagnosed in previously healthy patients during an 18
      month period in France. Eleven patients had skin or soft-tissue infections. Two
      patients died of CA-MRSA necrotizing pneumonia. A case of pleurisy occurred in a
      child who acquired CA-MRSA from his mother, who had a breast abscess. The Panton
      Valentine leukocidin genes and the lukE-lukD leukocidin genes were detected in
      all 14 isolates. The clonal origin of all of the isolates was demonstrated on the
      basis of their pulsotypes and antibiotic resistance profiles. All isolates had an
      agr3 allele. The combination of the Panton-Valentine leukocidin determinant
      (which encodes a virulence factor for primary skin infection and pneumonia) with
      the mecA gene (which confers antibiotic resistance and epidemicity) appears to
      have created a superadapted S. aureus strain that is spreading in the community.

PMID- 12228819
TI  - Randomized, placebo-controlled trial of atovaquone/proguanil for the prevention
      of Plasmodium falciparum or Plasmodium vivax malaria among migrants to Papua,
      Indonesia.
AB  - The increasing prevalence of resistance to antimalarial drugs reduces options for
      malaria prophylaxis. Atovaquone/proguanil (Malarone; GlaxoSmithKline) has been
      >95% effective in preventing Plasmodium falciparum malaria in lifelong residents
      of areas of holoendemicity, but data from persons without clinical immunity or
      who are at risk for Plasmodium vivax malaria have not been described. We
      conducted a randomized, double-blinded study involving 297 people from areas of
      nonendemicity in Indonesia who migrated to Papua (where malaria is endemic) < or
      =26 months before the study period. Subjects received prophylaxis with 1 Malarone
      tablet (250 mg of atovaquone and 100 mg of proguanil hydrochloride; n=148) or
      placebo (n=149) per day for 20 weeks. Hematologic and clinical chemistry values
      did not change significantly. The protective efficacy of atovaquone/proguanil was
      84% (95% confidence interval [CI], 44%-95%) for P. vivax malaria, 96% (95% CI,
      72%-99%) for P. falciparum malaria, and 93% (95% CI, 77%-98%) overall.
      Atovaquone/proguanil was well tolerated, safe, and effective for the prevention
      of drug-resistant P. vivax and P. falciparum malaria in individuals without prior
      malaria exposure who migrated to Papua, Indonesia.

PMID- 12228820
TI  - Molecular epidemiology of a citywide outbreak of extended-spectrum beta-lactamase
      producing Klebsiella pneumoniae infection.
AB  - Multidrug-resistant strains of Klebsiella pneumoniae are a problem in many
      hospitals. In 1999, the molecular epidemiology of K. pneumoniae with extended
      spectrum beta-lactamases (ESBLs) was studied at 15 hospitals in Brooklyn. Of 824
      unique patient isolates, 34% were presumptive ESBL producers. Of this subset, 34%
      were susceptible to cefoxitin, 42% to ciprofloxacin, 48% to ceftriaxone, 55% to
      piperacillin-tazobactam, 57% to amikacin, and 86% to cefepime. Ribotype analysis
      revealed 87 unique types. However, 2 clusters accounted for 35% of isolates and
      were present in most of the hospitals. One cluster was significantly more
      resistant to most antibiotics. Although there was a predominance of SHV-5,
      considerable heterogeneity of beta-lactamases was evident, even among isolates of
      the same cluster. A correlation was found between the use of cephalosporins and
      the prevalence of ESBL-producing strains of K. pneumoniae at each hospital. Our
      data suggest that there is an advanced outbreak of multidrug-resistant K.
      pneumonia infection that is affecting all Brooklyn hospitals.

PMID- 12228821
TI  - What is the relevance of obtaining multiple blood samples for culture? A
      comprehensive model to optimize the strategy for diagnosing bacteremia.
AB  - Through a heuristic and probabilistic approach, we evaluated blood culture
      operating characteristics (sensitivity, specificity, and predictive values) as a
      function of several pretest parameters, together with their variability. On the
      basis of a meta-analysis of quantitative data from the literature, a model was
      developed and an estimation of the operating characteristics through numerical
      simulations (Monte Carlo method) was performed. The model evaluates the influence
      of ordering and drawing parameters on the ability of blood culture to distinguish
      bacteremic from nonbacteremic patients, regardless of the causative species. By
      considering the total blood volume to be cultured (six 5-10-mL bottles), results
      were found to confirm the current guidelines. On the basis of this hypothesis,
      the results, together with an analysis of the literature, failed to show any
      benefit of a strategy that involves obtaining multiple samples. The best strategy
      when performing blood culture is to obtain blood for 6 bottles (for a total
      volume of 35-42 mL), preferably at the same time.

PMID- 12228822
TI  - Management of anthrax.
AB  - From 3 October 2001 through 16 November 2001, in the United States, there were 18
      confirmed cases of inhalational and cutaneous anthrax, an additional 4 suspected
      cases of cutaneous anthrax, and 5 deaths due to inhalational anthrax. Although
      the number of cases was relatively small, this experience brought bioterrorism
      and its potential to sharp focus as thousands of people began receiving
      prophylactic antibiotics after possible exposure to anthrax spores. These events
      have resulted in a substantial impact on the health care system, including the
      rewriting of pneumonia guidelines, new emphasis on identification of microbial
      etiology, substantial infusion of funds for bioterrorism-related research, and a
      sudden mandate for regional disaster and public health planning. This article
      provides clinicians with clinically relevant information about the diagnosis and
      management of anthrax.

PMID- 12228823
TI  - Bacterial contamination of animal feed and its relationship to human foodborne
      illness.
AB  - Animal feed is at the beginning of the food safety chain in the "farm-to-fork"
      model. The emergence of variant Creutzfeldt-Jakob disease has raised awareness of
      the importance of contaminated animal feed, but less attention has been paid to
      the role of bacterial contamination of animal feed in human foodborne illness. In
      the United States, animal feed is frequently contaminated with non-Typhi
      serotypes of Salmonella enterica and may lead to infection or colonization of
      food animals. These bacteria can contaminate animal carcasses at slaughter or
      cross-contaminate other food items, leading to human illness. Although tracing
      contamination to its ultimate source is difficult, several large outbreaks have
      been traced back to contaminated animal feed. Improvements in the safety of
      animal feed should include strengthening the surveillance of animal feed for
      bacterial contamination and integration of such surveillance with human foodborne
      disease surveillance systems. A Hazard Analysis and Critical Control Point
      program should be instituted for the animal feed industry, and a Salmonella
      negative policy for feed should be enforced.

PMID- 12228824
TI  - Ganciclovir-resistant cytomegalovirus in organ transplant recipients.
AB  - Ganciclovir-resistant (GanR) cytomegalovirus (CMV) is an emerging clinical
      problem in organ transplant recipients, particularly recipients of kidney and
      pancreas and lung transplants. GanR CMV, a late posttransplantation complication,
      is observed predominantly among CMV-seronegative recipients of organs from
      seropositive donors, especially among recipients receiving intensive
      immunosuppression and having prolonged exposure to ganciclovir. Given the
      limitations of current diagnostic methods, if GanR CMV is clinically suspected,
      empirical treatment with intravenously administered foscarnet should be used in
      conjunction with reductions in immunosuppressive therapy and possibly CMV
      hyperimmune globulin. Better diagnostic tools and newer, less-toxic antiviral
      agents with different mechanisms of action are urgently needed to decrease the
      morbidity associated with this complication in organ transplant recipients.

PMID- 12228825
TI  - Review of the effect of highly active antiretroviral therapy on hepatitis C virus
      (HCV) RNA levels in human immunodeficiency virus and HCV coinfection.
AB  - The effect of anti-human immunodeficiency virus (HIV) treatment on hepatitis C
      virus (HCV) RNA levels in HIV-HCV-coinfected persons is uncertain. Although it is
      commonly believed that, with the initiation of HIV treatment, there may be an
      initial increase followed by a gradual decrease of HCV RNA levels to lower than
      those at pretreatment, the published studies evaluating this are of small and
      heterogeneous populations, are limited in follow-up, and have conflicting
      results. A prospective clinical trial of sufficient size and duration may help
      clarify this issue. This may be clinically relevant, because lower HCV RNA levels
      are a predictive factor for favorable response to HCV antiviral therapy.

PMID- 12228826
TI  - Human herpesvirus 8-positive Castleman disease in human immunodeficiency virus
      infected patients: the impact of highly active antiretroviral therapy.
AB  - We report the case histories of 7 human immunodeficiency virus (HIV)-infected
      patients receiving highly active antiretroviral therapy (HAART) who had a
      diagnosis of Castleman disease. All 6 patients who were treated responded to
      chemotherapy; immune reconstitution was observed in 5 patients, but it did not
      prevent relapse of Castleman disease. However, the mean duration of survival
      observed in this series (48 months) was most probably due to immune
      reconstitution resulting from receipt of HAART, which reduced the mortality
      associated with HIV disease.

PMID- 12228827
TI  - Antiretroviral drug resistance mutations in antiretroviral-naive prisoners.
AB  - We assessed the incidence of antiretroviral drug resistance in a cohort of 25
      antiretroviral-naive, human immunodeficiency virus-positive inmates in
      Massachusetts. Silent mutations, unexpected mutations at resistant sites, and
      resistance mutations were recorded. Among these inmates, we found a prevalence of
      drug resistance mutations that was equivalent to the prevalence previously found
      in nonprison populations in the same state.

PMID- 12228828
TI  - Diagnosis and treatment of Aspergillus flavus sternal wound infections after
      cardiac surgery.
AB  - We report the clinical data for 9 patients affected during an outbreak of
      Aspergillus flavus sternal wound infections after cardiac surgery. In 7 patients,
      the infection had a locally invasive character, with 3 of these patients having
      multiple relapses; 2 patients had fulminant mediastinitis and died. Most patients
      received combined surgical and medical treatment.

PMID- 12228830
TI  - Lipid formulations of amphotericin B for empirical treatment of fever and
      neutropenia.

PMID- 12228829
TI  - Lipid formulations of amphotericins: are you a lumper or a splitter?

PMID- 12228832
TI  - Mortality associated with breakthrough candidemia among patients with and those
      without cancer.

PMID- 12228834
TI  - Patients with bacteremia who were discharged from the emergency department.

PMID- 12228837
TI  - Stevens-Johnson syndrome associated with abacavir therapy.

PMID- 12228836
TI  - Colistin: an antimicrobial for the 21st century?

PMID- 12228838
TI  - Successful treatment of Enterococcus faecalis prosthetic valve endocarditis with
      linezolid.

PMID- 12228839
TI  - Central venous catheter-related bacteremia due to Tsukamurella species in the
      immunocompromised host: a case series and review of the literature.
AB  - We report 6 cases of bacteremia due to Tsukamurella species, all of which were in
      immunosuppressed patients with indwelling central venous catheters (CVCs). Fewer
      than 20 cases of serious illness due to these gram-positive bacilli have been
      reported in the medical literature; these cases have mostly been ascribed to the
      species Tsukamurella paurometabola. Tsukamurella species are frequently
      misidentified as Rhodococcus or Corynebacterium species. We used high-performance
      liquid chromatography to identify these organisms to the genus level and 16S
      ribosomal RNA gene sequencing and DNA-DNA dot blots for species identification.
      Three of our isolates were identified as Tsukamurella pulmonis, 1 was identified
      as Tsukamurella tyrosinosolvans, and 1 was identified as a unique species. One
      isolate was not maintained long enough for species identification. All patients
      were successfully treated with antimicrobial therapy and CVC removal. Infection
      with this organism should be considered in the immunosuppressed patient with an
      indwelling CVC and gram-positive bacilli in the blood.

PMID- 12228840
TI  - Voriconazole treatment of disseminated paecilomyces infection in a patient with
      acquired immunodeficiency syndrome.
AB  - We describe a patient with poorly controlled, multidrug-resistant human
      immunodeficiency virus disease who developed >20 skin lesions caused by
      Paecilomyces lilacinus. The lesions failed to improve during treatment with oral
      itraconazole, amphotericin B, and amphotericin B lipid complex but improved
      during treatment with voriconazole.

PMID- 12228843
TI  - The SCOPE trial. Study on Cognition and Prognosis in the Elderly.
AB  - The Study on Cognition and Prognosis in the Elderly (SCOPE) was designed to
      provide outcome data on cardiovascular endpoints and cognitive function in 4500
      elderly hypertensive patients randomised to the angiotensin receptor blocker,
      candesartan, or to placebo and followed up for 4.5 years. The primary endpoint of
      combined cardiovascular mortality, non-fatal myocardial infarction and non-fatal
      stroke was not significantly reduced by active treatment (relative risk reduction
      11%, p=0.19). There was also no significant difference in the decline of
      cognitive function between the two treatment arms. Active treatment of the
      placebo group (mainly hydrochlorothiazide) reduced the blood pressure differences
      between the treatment arms to only 3.2/1.6 mmHg, thus markedly reducing the
      overall power of the study. In a number of non-prespecified subgroup analyses,
      advantages of candesartan over placebo were reported.

PMID- 12228842
TI  - A new essential hypertension susceptibility locus on chromosome 2p24-p25,
      detected by genomewide search.
AB  - Essential hypertension (EH) is a complex disorder that results from the
      interaction of a number of susceptibility genes and environmental factors. We
      studied an isolated Sardinian village (Talana) in which the prevalence of
      hypertension is comparable to that in most Western populations. Talana exhibits
      features, such as slow demographic growth, high inbreeding, a low number of
      founders, stable lifestyle and culture, and accurate genealogical records, that
      make it suitable for the study of complex disorders. Clinical assessment of the
      entire adult population (N= approximately 1,000) identified approximately 100
      hypertensive subjects. For our study, we selected the individuals with the most
      severe EH (i.e., diastolic blood pressure >100 mm Hg), belonging to a single deep
      rooted pedigree (12 generations), whose common ancestors lived in the 17th
      century. We performed a three-stage genomewide search using 36 affected
      individuals, by means of parametric linkage and allele-sharing approaches. LOD
      scores >1 were observed on chromosomes 1, 2, 13, 15, 17, and 19 (stage I). The
      most striking result was found in a 7.57-cM region on chromosome 2p24-p25. All
      five nonparametric linkage statistics estimated by the SimWalk2 program lie above
      the significance threshold of P<.008 for the whole region. Similar significance
      was obtained for 2p24-25 when parametric linkage (LOD score 1.99) and linkage
      disequilibrium mapping (P=.00006) were used, suggesting that a hypertension
      susceptibility locus is located between D2S2278 and D2S168. This finding is
      strengthened by a recent report of linkage with marker D2S168 in a hypertensive
      sib-pair sample from China.

PMID- 12228844
TI  - Rationale for combination therapy in the treatment of hypertension.
AB  - The effective treatment of hypertension still poses many problems. In the last
      decade it has become apparent that in many patients multi-drug regimens are
      needed to effect blood pressure control. How best to combine medications and what
      might be a preferred order of initiating drugs is still open to debate and has
      proven the substance of many of the published guidelines on this theme. Like most
      matters in the clinical sector the approach to a disease   in this case
      hypertension   should remain highly individualised and cognisant of what can be
      significant cost considerations.

PMID- 12228845
TI  - The practical aspects of combination therapy with angiotensin receptor blockers
      and angiotensin-converting enzyme inhibitors.
AB  - Angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor
      blockers (ARBs) are widely prescribed for the management of hypertension. ACE
      inhibitors (ACE-I) and, more recently, ARBs have an established track record of
      success in the treatment of congestive heart failure (CHF), proteinuric renal
      disease and most recently the hypertensive patient with a high cardiac-risk
      profile. The individual success of each of these drug classes has fuelled
      speculation that given together the overall effect of both would exceed that of
      either given alone. This premise, although biologically plausible, has yet to be
      proven in a convincing enough fashion to support the routine use of these two
      drug classes in combination. Additional clarifying studies are needed to
      establish whether specific patient subsets exist that might benefit from such
      combination therapy.

PMID- 12228846
TI  - Combining renin-angiotensin-aldosterone system blockade with diuretic therapy for
      treatment of hypertension.
AB  - The rationale for using angiotensin-converting enzyme inhibitors (ACE-I) or
      angiotensin receptor blockers (ARBs) in combination with thiazide diuretic
      therapy has centred formerly around antihypertensive synergy and counter
      balancing adverse metabolic effects, particularly on potassium homeostasis.
      However, two recent landmark clinical trials that included high-risk hypertensive
      patients have now provided an evidence base for this form of combination therapy
      by demonstrating the efficacy of perindopril/indapamide and losartan/
      hydrochlorothiazide in reducing vascular morbidity and mortality, a proportion of
      the benefit being unaccounted for by blood pressure reduction alone. Several
      unresolved issues remain concerning class effects versus specific drug effects,
      optimal dosing, potential differences in efficacy between ACE-I and ARBs, whether
      elderly mild hypertensives benefit from this form of combination therapy, and the
      possibility that the optimal regimen may be a triple combination of ACE-I, ARB
      and thiazide diuretic. These issues will be resolved by ongoing and future major
      endpoint trials in hypertension.

PMID- 12228847
TI  - Calcium channel blockade in combination with angiotensin-converting enzyme
      inhibition or angiotensin II (AT(1)-receptor) antagonism in hypertensive
      diabetics and patients with renal disease and hypertension.
AB  - Effective reduction in blood pressure (BP) improves survival and morbidity in
      hypertensive patients. Combination therapy with multiple antihypertensive agents
      is frequently required in clinical practice and therapeutic trials to achieve
      target BP. Patients at elevated cardiovascular risk achieve the greatest benefit
      from equivalent reduction in BP and also require more stringent BP control. In
      patients with hypertension and diabetes mellitus or renal disease, BP control is
      of primary importance and blockade of the renin-angiotensin system (RAS) should
      be the initial therapeutic intervention. Choice of combination therapy has been
      insufficiently studied in major clinical cardiovascular endpoint trials. Diuretic
      therapy remains the logical addition to RAS blockade. Despite previous debate,
      the available evidence suggests long-acting calcium-channel blockers are also a
      safe and very effective addition to improve BP control further. The choice of
      antihypertensive combination therapy should not override the fundamental
      necessity of lowering BP to target levels.

PMID- 12228848
TI  - Vasopeptidase inhibitors.
AB  - Vasopeptidase inhibitors are a new class of drugs that have dual inhibitory
      effects on two key enzymes involved in the metabolism of vasoactive peptides.
      Essentially, they inhibit angiotensin-converting enzyme (ACE), thereby blocking
      the generation of angiotensin II (Ang II); at the same time they prevent the
      breakdown of natriuretic peptides by the enzyme neutral endopeptidase. The
      combination of reduction of Ang II on a background of increased natriuretic
      peptide activity has several potential advantages for the treatment of
      cardiovascular and renal disease and in particular, hypertension and congestive
      heart failure (CHF). Several vasopeptidase inhibitors, such as sampatrilat,
      fasidotril, gemopatrilat and omapatrilat (Vanlev, the most clinically developed
      vasopeptidase inhibitor to date) are under intensive clinical investigation.
      Recent clinical trials have demonstrated effective antihypertensive activity in
      hypertension, independent of age, renin and salt status or ethnic origin, and
      have also highlighted the potential for vasopeptidase inhibition as a new
      therapeutic modality for the treatment of CHF. Moreover, ongoing research
      suggests that this new class of drugs may be an important approach, not only for
      the treatment of hypertension and of conditions associated with overt volume
      overload but also for ischaemic heart disease.

PMID- 12228849
TI  - Renin-angiotensin system antagonism and lipid-lowering therapy in cardiovascular
      risk management.
AB  - The renin-angiotensin system (RAS) and dyslipidaemia have been shown to be
      involved in the genesis and progression of atherosclerosis. Manipulation of the
      RAS has been effective in modifying human coronary artery disease progression.
      Similarly, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase
      inhibitors or  statins  have been shown to reduce cholesterol and lower
      cardiovascular events in primary and secondary prevention trials in coronary
      artery disease. In addition to their primary mode of action, statins and blockers
      of the RAS possess common additional properties that include restoration of
      endothelial activity and inhibition of cellular proliferation. This article
      reviews the current data on the common properties of these classes of drugs in
      which the beneficial effects extend beyond their antihypertensive and lipid
      lowering properties.

PMID- 12228850
TI  - The frequent need for three or more drugs to treat essential hypertension. What
      evidence for optimal combinations?
AB  - Treatment of high blood pressure (BP) reduces the risk of death and morbidity
      from stroke and coronary heart disease. There is accumulating evidence from large
      outcome studies that support a move towards lower treatment targets in
      hypertensives, particularly for those with concomitant risk factors or evidence
      of established target organ damage. At present, the achieved rates for BP control
      in the UK are very poor. Amongst the many possible reasons for poor BP control is
      the under utilisation of effective drug combinations. This article addresses the
      rationale for two and three drug combination therapy in hypertension and reviews
      the trial evidence for efficacy of combinations.

PMID- 12228851
TI  - Age-related increase of pulse pressure and gene polymorphisms in essential
      hypertension: a preliminary study.
AB  - Genes may modulate the changes of blood pressure (BP) with age; this possibility
      has never been studied for the age-related increase of pulse pressure (PP),
      although in older populations, PP is considered the stronger mechanical factor
      predicting cardiovascular mortality. In humans, the presence of the mutant allele
      C of the angiotensin II (Ang II) AT(1)-receptor or of the mutant allele T of the
      eNOS G(298) T gene polymorphisms is associated with enhanced contractile
      properties of conduit arteries in response to vasoconstrictive agents. In this
      study, we evaluated, in subjects with untreated essential hypertension, whether
      the presence of these mutant alleles or their combination might influence the age
      related increase of PP. Three main findings emerged from the study and were
      particularly observed in women: 1) the presence of the C and/or of the T mutant
      alleles or their combination were associated with a steeper slope of the age
      versus PP curve, compared with subjects without the mutant allele; 2) the slope
      was more significantly enhanced when the two mutant alleles were associated in
      the same genotype; and 3) no comparable age- and gender-related changes in
      systolic, diastolic or mean BP were found according to this genetic
      classification. In subjects with essential hypertension, genes may modulate the
      age-mediated increase of PP. This finding gives new insights in the interactions
      between genes, mechanical factors and cardiovascular risk.

PMID- 12228853
TI  - Lack of rapid aldosterone effects on forearm resistance vasculature in health.
AB  - OBJECTIVES: Systemic infusions of aldosterone cause an acute increase in systemic
      vascular resistance (SVR) in healthy subjects. It is not clear whether this is
      due to a direct effect on the vasculature or the result of increased sympathetic
      tone. We investigated the short-term effects of locally infused aldosterone on
      the forearm resistance bed. METHODS: In this dose response study, we assessed the
      effects of incremental doses (10, 50, 100 ng/minute) of intrabrachial aldosterone
      on forearm blood flow (FBF), using conventional strain gauge plethysmography.
      Arterial blood pressure was monitored continuously, using finger photo-
      plethysmography. Forearm vascular resistance (FVR) was calculated. FBF and FVR
      were also measured in the non-infused arm. Changes in FBF and FVR in the infused
      arm were corrected for those occurring in the control arm. RESULTS: Plasma
      aldosterone levels in the venous effluent of the infused arm increased in a dose
      dependent fashion, from 113.3+/-17.9 pg/ml at baseline to 297.8+/-51.8 pg/ml at
      10 ng/minute (p=<0.01), 743.9+/-105.9 pg/ml at 50 ng/min (p=<0.001 vs. baseline)
      and 1230.6+/-73.7 pg/ml at 100 ng/min (p=<0.0005 vs. baseline). Plasma
      concentrations of aldosterone in the control arm did not change significantly vs.
      baseline. The corrected FBF (+4.1+/-10.3%) and corrected FVR (+4.3+/-11.3%) did
      not change significantly even at peak infusion rates. CONCLUSIONS: Local intra
      arterial infusion of aldosterone had no acute effect on forearm resistance
      vessels in healthy male volunteers.

PMID- 12228852
TI  - Comparison of the effects of antihypertensive treatment with angiotensin II
      blockade and beta-blockade on carotid wall structure and haemodynamics: protocol
      and baseline demographics.
AB  - Several systemic factors have been shown to contribute to the acceleration of
      large vessel atheroma. Correction of these factors leads to a reduction in the
      progression of plaque formation and associated arterial wall thickness. Atheroma
      remains, however, a focal disease, developing at characteristic sites within the
      arterial tree. These sites are typically at areas of vessel branching or marked
      curvature, and correspond to regions of high tensile stress and low sheer stress,
      leading to the hypothesis that local haemodynamic factors and vessel wall
      mechanics potentiate the focal development of atheroma. Current assessment of
      vascular haemodynamics suffers from an inability to handle complex flow, and does
      not allow accurate determination of locally varying flow, and shear stress
      patterns. The application of computational fluid dynamic (CFD) flow simulation
      techniques to ultrasound and local pressure data, however, allows a
      comprehensive, non-invasive appraisal of haemodynamic flow parameters to be
      performed. The Candesartan cilexetil and Atenolol Carotid Haemodynamic Endpoint
      Trial (CACHET) study compares the effects of two antihypertensive regimens, one b
      blocker-based, the other angiotensin receptor blocker based, on carotid intima
      media thickness. The collection of ultrasound and pressure data on each subject
      provides a unique opportunity to apply these data to the CFD model to study the
      effects of these antihypertensive regimens on local fluid dynamics. This will
      lead to a greater understanding of the relationship of these factors to atheroma
      formation and regression.

PMID- 12228854
TI  - High plasma adrenomedullin concentrations in patients with high-renin essential
      hypertension.
AB  - Adrenomedullin (AM) is a novel peptide, first isolated from human
      phaeochromocytoma, which elicits a long-lasting vasorelaxant activity. Recently,
      it has been reported that endothelial cells produce AM and that immunoreactive AM
      plasma levels may be elevated in human arterial hypertension, although the exact
      pathophysiological role of AM remains to be established. The aim of our study was
      to determine the relationship between the components of the enin-angiotensin
      aldosterone system (RAAS) and plasma AM levels in patients with low-, medium- or
      high- renin essential hypertension. The study groups included 10 patients with
      low-renin essential hypertension (average age 42+15 years), nine patients with
      medium-renin essential hypertension (46+13 years), 11 patients with high-renin
      essential hypertension (42+14 years) and 12 healthy subjects (43+11 years). Our
      results demonstrated that the mean AM values of all patients with essential
      hypertension were 10.85+3.14 pg/ml; there was a statistical correlation (r=0.705;
      p<0.001) between plasma renin activity (PRA) and AM levels in hypertensives. In
      patients with high-renin essential hypertension, plasma AM levels (14.2+2.2
      pg/ml) were significantly higher (p<0.001) than those of healthy subjects
      (8.7+2.1 pg/ml), patients with medium-renin essential hypertension (8.5+1.4
      pg/ml), and patients with low-renin essential hypertension (9.1+1.5 pg/ml). There
      was no statistical difference in AM concentrations between medium- and low-renin
      hypertensive patients. In conclusion, we have found that, in hypertensive
      patients, plasma AM levels were increased only in high-renin individuals,
      suggesting a role of AM in this particular form of human essential hypertension.

PMID- 12228855
TI  - Nephrectomy and peritoneal dialysis eliminates circulating renin and controls
      uraemia in the rat.
AB  - OBJECTIVE: The aim of the present study was to develop a rat model for in vivo
      studies of the local effects of the renin-angiotensin system (RAS) following
      elimination of circulating renin. METHODS: Sprague Dawley rats were bilaterally
      nephrectomised and had a peritoneal dialysis catheter implanted. The rats were
      maintained on dialysis continuously for 48 hours, using Dianeal PD4 3.86% glucose
      dialysis solution. The peritoneal catheter and an automated system for dialysate
      exchange were made in our laboratory. A sham nephrectomised control group of rats
      was also dialysed. RESULTS: Nephrectomised and sham-operated rats remained active
      and in good general condition during peritoneal dialysis. At 48 hours, in
      nephrectomised, dialysed rats, peritoneal urea clearance was 4.14+/-0.52 ml/hour,
      plasma urea was 40.0+/-7.7 mmol/L, plasma creatinine was 0.423+/- 0.070 mmol/L
      and plasma renin was below the limit of detection. CONCLUSIONS: In conclusion, it
      was possible to sustain bilaterally-nephrectomised rats on continuous peritoneal
      dialysis for 48 hours, pending elimination of renin from the circulation. The
      nephrectomised dialysed rat model should be useful for investigation of the
      physiological effects of the circulating versus the local RAS.

PMID- 12228856
TI  - Renal graft failure after addition of an angiotensin II receptor antagonist to an
      angiotensin-converting enzyme inhibitor: unmasking of an unknown iliac artery
      stenosis.
AB  - Combined treatment with an angiotensin-converting enzyme (ACE) inhibitor and an
      angiotensin II (Ang II) receptor blocker (ARB) has been suggested in order to
      achieve a more complete blockade of the renin-angiotensin-aldosterone system in
      cardiovascular and renal disease. The present report describes a case of acute
      renal graft dysfunction following the addition of an ARB to existing ACE
      inhibition. This unmasked an unknown iliac artery stenosis. The case indicates a
      possible important role of Ang II generated by non-ACE pathways in this
      situation.

PMID- 12228857
TI  - Grossly elevated serum angiotensin-converting enzyme activities are still
      suppressible with ACE inhibitor therapy.

PMID- 12228859
TI  - The residency review committee for surgery: Structure and function.

PMID- 12228860
TI  - The American Board of Surgery and the ABMS: The role of boards.

PMID- 12228861
TI  - Certification in vascular surgery as it stands today.

PMID- 12228862
TI  - Credentialing for hospital privileges in vascular surgery.

PMID- 12228863
TI  - New training pardigms: The four-plus program.

PMID- 12228864
TI  - New training paradigms: The three-plus-three program.

PMID- 12228865
TI  - Endovascular qualifications for practicing surgeons.

PMID- 12228866
TI  - Accreditation and credentialing in the vascular laboratory.
AB  - The vascular diagnostic laboratory remains an integral component of the vascular
      surgeon's practice and has replaced many invasive techniques for the diagnosis
      and treatment plan of vascular disease. Although financial challenges have been
      leveled at the vascular laboratory, the actual number of laboratories continues
      to increase, suggesting a greater demand for vascular laboratory studies. With
      this, also comes the challenge of maintaining quality within each laboratory as
      well as ensuring a standard of quality for all laboratories nationwide.
      Credentialing and accreditation have been used for this purpose in nearly all
      areas of medicine and have provided a mechanism for assuring a minimum standard
      of competency. Over the last decade, similar mechanisms have been applied toward
      the vascular diagnostic laboratory, which likely have resulted in improved
      vascular diagnostic studies and overall care.

PMID- 12228867
TI  - Acquisition and maintenance of surgical competence.
AB  - Rapidly developing and emerging technologies, unprecedented scientific advances,
      significant changes in societal expectations, intense focus on physician
      competence, concerns regarding patient safety, and new mandates all have had a
      major impact on both surgical practice and surgical education. The definition of
      6 general competencies by the Accreditation Council for Graduate Medical
      Education and the American Board of Medical Specialties and the introduction of
      the concept of maintenance of certification require surgical educators, and
      indeed all surgeons, to reevaluate the methods currently in use to ensure
      competence in surgery. The multidimensional aspects of competence make
      verification and certification of a competent surgeon an extremely challenging
      task. However, a combination of traditional and innovative approaches may be used
      to facilitate achievement of the general competencies. Such approaches should be
      based on principles of adult education and experiential learning. Education
      research has yielded valuable information on the validity and reliability of a
      number of innovative methods that may be used to teach and assess several general
      competencies. Additional efforts are needed to address the other competencies
      effectively using novel approaches. The American College of Surgeons and other
      surgery specialty societies are well positioned to play a pivotal role in
      supporting the learning needs of practicing surgeons, residents, and medical
      students within the context of the general competencies and facilitating their
      continuing professional development.

PMID- 12228868
TI  - Documentation of competency: Maintaining an outcomes database.
AB  - Medical practice in the 21st century will include increased scrutiny of the
      competency of vascular surgeons measured in large part by treatment outcomes. At
      least part of the drive behind this is that the public demand for clinical
      competency of its doctors is greater than ever as the unassailable position of
      the "all-knowing physician" is (appropriately) vanishing. Two general types of
      variables need to be considered in the assessment of treatment outcomes: key
      outcome variables and key process variables. Key outcome variables are the
      critical results from a treatment plan, whereas key process variables affect
      these results. Ideal tracking methods do not exist in most hospital systems, and
      many variables are out of the control of the individual surgeon. Difficulties
      recording and reporting outcomes and determining competencies are numerous, but
      vascular surgeons must accept and overcome these difficulties. Standardized
      definitions for preoperative, surgical, and postoperative variables as well as
      treatment results must be decided before attempting to determine competency. Once
      the variables and definitions to define competency are determined, commercially
      available computer software can make the task of data recording and data output
      realistic. Eventually, systemwide "enterprise" solutions from computer companies
      will make this task even more uncomplicated.

PMID- 12228869
TI  - What does the Leapfrog Group portend for physicians?

PMID- 12228870
TI  - Cancer patients' sources of information: use and quality issues.
AB  - Appropriate information, offered at the right time, has been recognised as a key
      factor in enabling patients to cope with a diagnosis of cancer. This paper
      describes the sources of information that are currently being utilised by
      patients and the perceived quality of these sources. A sample of 430 patients
      were asked to indicate on a series of Likert scales their views of 19 commonly
      available sources of information. The most frequently cited sources of
      information were the hospital consultant, General Practitioner,
      chemotherapy/radiotherapy staff, ward staff and family/friends. It is of interest
      that the internet was only used by under 10% of patients. The source that scored
      the highest in terms of quality of information was the specialist/Macmillan
      nurses. GPs and written material scored poorly in terms of quality of
      information. The relationship between information and sources, gender, age and
      diagnosis was also examined. Age was found to have the greatest influence on the
      perceived quality of information and the frequency of its use. The paper
      concludes that there is a need for improvement in the provision of information by
      the primary health care team. The issue of the quality of written information
      available for patients requires further investigation to identify the type of
      written material used. Furthermore, family/friends should be recognised as
      important sources of information to many patients. Finally, there is a need for
      more specialist nurses, as they are clearly the preferred source of information
      for the majority of cancer patients.

PMID- 12228871
TI  - The effects of interactive music therapy on hospitalized children with cancer: a
      pilot study.
AB  - BACKGROUND: The use of music therapy with children in health settings has been
      documented, but its effectiveness has not yet been well established. This pilot
      study is a preliminary exploration of the effectiveness of interactive music
      therapy in reducing anxiety and increasing the comfort of hospitalized children
      with cancer. METHODS: Pre- and post-music therapy measures were obtained from
      children (N = 65) and parents. The measures consisted of children's ratings of
      mood using schematic faces, parental ratings of the child's play performance, and
      satisfaction questionnaires completed by parents, children and staff. RESULTS:
      There was a significant improvement in children's ratings of their feelings from
      pre- to post-music therapy. Parents perceived an improved play performance after
      music therapy in pre-schoolers and adolescents but not in school-aged children.
      Qualitative analyses of children's and parents' comments suggested a positive
      impact of music therapy on the child's well-being. CONCLUSIONS: These preliminary
      findings are encouraging and suggest beneficial effects of interactive music
      therapy with hospitalized pediatric hematology/oncology patients. In future
      studies replicating these findings should be conducted in a randomized control
      trial.

PMID- 12228872
TI  - Exercise participation after diagnosis of breast cancer: trends and effects on
      mood and quality of life.
AB  - Individuals treated for cancer often experience higher levels of emotional
      distress than the general population. Previous research has shown that exercise
      can have an ameliorating effect on these problems. This 12-month prospective
      longitudinal study investigated mood, quality of life, cancer-related symptoms,
      and exercise behavior of 69 women who had completed treatment for Stage 0-2
      breast cancer. We studied the natural progression of exercise participation after
      cancer treatment. Effects on mood, quality of life, and cancer-related symptoms
      were assessed after controlling for demographic variables, disease variables,
      social support, and baseline values to test the hypothesis that women who
      exercised were more likely to report better mood, higher quality of life, and
      fewer cancer-related symptoms. Results indicated that women did not increase
      their exercise participation over time and that overall mean minutes of exercise
      participation were below recommended levels. Baseline demographic predictors of
      exercise participation included younger age, having a spouse or partner,
      increased time since diagnosis, higher social support, and higher depression.
      Exercise participation was associated with improved physical functioning, but not
      overall mood or cancer-related symptoms. We discuss implications of these
      findings towards the well-being of breast cancer survivors.

PMID- 12228873
TI  - Coping and health-related quality of life in men with prostate cancer randomly
      assigned to hormonal medication or close monitoring.
AB  - Prostatic carcinoma and its treatment have been associated with adverse effects
      on health-related quality of life (HRQoL). Individual differences in appraisal
      and coping have been suggested to mediate these HRQoL outcomes. A randomized
      trial of 65 men with non-localized prostate cancer compared several treatments
      and tested associations between appraisal, coping, and HRQoL. These patients, and
      16 community volunteers matched for age and general health, undertook
      psychosocial assessments before treatment and after 6 months of treatment.
      Compared with baseline assessments, men on hormonal treatments reported impaired
      sexual function. Groups did not differ on emotional distress, existential
      satisfaction, subjective cognitive function, physical symptoms, or social and
      role functioning. For individuals, hormonal treatments were more frequently
      associated with decreased sexual, social and role functioning, but were also
      associated with improved physical symptoms. In hierarchical regression analysis,
      HRQoL was lower for men who had more comorbid illnesses, a history of
      neurological dysfunction, higher threat appraisals, or higher use of coping
      strategies at baseline. These results showed that pharmacological hormonal
      ablation for prostate cancer can improve or decrease HRQoL in different domains.
      HRQoL in men with prostate cancer was associated more strongly with appraisal and
      coping than with medical variables.

PMID- 12228874
TI  - Predicting worry following a diagnosis of breast cancer.
AB  - Measures identified in research as being predictive of later worry following a
      cancer diagnosis may be too time consuming for routine clinical screening
      purposes. In practice, therefore, clinicians may use factors such as disease
      severity to anticipate likely distress. In this study we evaluated alternative
      predictors based on simple ratings that we had found useful with other patient
      groups. METHODS: Women attending a breast clinic were briefly interviewed on
      three occasions about their worries: in the clinic immediately before diagnosis
      and twice after diagnosis, two and four months later. Severity of disease was
      established using the Nottingham Prognostic Index (NPI). RESULTS: Severity as
      assessed by the NPI was not highly correlated with post-diagnostic health
      worries. The factor found to be most highly correlated with subsequent worry
      about cancer was patients' ratings of the frequency of thinking about the initial
      clinic visit during the preceding week. CONCLUSION: Given the relative ease of
      asking about level of pre-diagnostic intrusive thoughts, we conclude that this
      index would provide a useful and practical method for clinicians to identify in
      advance those patients likely to worry excessively following a diagnosis of
      cancer.

PMID- 12228875
TI  - Explaining quality of life with crisis theory.
AB  - Based on the premises of crisis theory, we expected cancer patients in-crisis to
      report a poorer quality of life (QL) and cancer patients post-crisis to report a
      similar level of overall QL in comparison to healthy individuals. To explain
      these hypothesized findings, we expected the coping resources and strategies of
      patients in-crisis to be equally effective and those of patients post-crisis to
      be more effective as compared to those of healthy individuals. The sample
      consisted of: (a) 217 consecutive cancer patients in the acute phases of their
      illness (patients in-crisis); (b) 192 disease-free cancer patients (patients post
      crisis); and (c) 201 randomly selected healthy individuals. Established measures
      of QL, self-esteem and neuroticism (coping resources) and coping behavior (coping
      strategies) were mailed. As expected, patients in-crisis reported a poorer QL (p
      < 0.001) and patients post-crisis a similar overall QL as compared to healthy
      individuals. There were no significant or systematic differences between the mean
      levels of coping resources and strategies between the respective groups. Two-way
      analysis of variance indicated a group X coping resource interaction effect on
      overall QL for self-esteem (p < 0.01). As expected, the amount of variance of
      overall QL explained by self-esteem was largest for patients post-crisis (27%)
      and comparable for patients in-crisis and healthy individuals (10 and 11%).
      Patients in-crisis were not able to make their coping resources and strategies
      more effective, whereas patients post-crisis seemed to have enhanced the
      effectiveness of self-esteem in restoring their QL as compared to healthy
      persons.

PMID- 12228876
TI  - Psychosocial intervention for lesbians with primary breast cancer.
AB  - This study examined the effects of a Supportive-Expressive group therapy
      intervention offered to lesbians with early stage breast cancer. Twenty lesbians
      diagnosed with breast cancer in the previous 12-months were recruited and
      assessed at baseline, and at 3, 6, and 12 months after the group intervention.
      During the 12-week intervention, group members focused on the problems of a new
      diagnosis, coping with the illness and treatment, mood changes, coping responses
      and self-efficacy, improving relationships with family, friends and physicians,
      the impact of the illness on life, pain and sleep, and changes in body image and
      sexuality. A within-subject slopes analysis was conducted on data collected for
      each woman over the first year. As predicted, women reported reduced emotional
      distress, intrusiveness, and avoidance, and improved coping. There were
      significant changes in their social support, but in the unexpected direction.
      Instrumental support and informational support declined. However, conflict in
      family relations also declined, while trends were found towards more cohesiveness
      and expressiveness. Participants reported less pain and better sleep. There were
      no changes in body image, sexuality, or attitudes toward health-care providers.
      These results suggest that Supportive/Expressive group intervention appears to be
      helpful for lesbians with breast cancer.

PMID- 12228877
TI  - Providing internet lessons to oncology patients and family members: a shared
      project.
AB  - The paper describes the steps in a pilot study taken to develop and evaluate an
      Internet intervention for cancer patients and family members. The intervention
      was a shared project of two hospital departments; a volunteer oncology support
      service, Hope & Cope, and the Health Services Library. Forty subjects were
      surveyed on their computer use and interest, and of these, half used the Internet
      to access health and medical information. Of the 40 subjects, 28 participated in
      an innovative, one-to-one teaching session with a medical librarian where they
      learned to access Internet sites to find information specific to their needs and
      subsequently be more confident in their perceived ability to evaluate the
      information received. Follow up interviews found that the sessions were well
      received and at two months follow-up the participants attributed their positive
      well being in large part to the intervention. Internet use by oncology patients
      and family members in conjunction with skilled help has the potential to
      contribute in a timely fashion to the well being of those with cancer.

PMID- 12228878
TI  - A pilot study of group exercise training (GET) for women with primary breast
      cancer: feasibility and health benefits.
AB  - Evidence is accumulating for physical activity as an effective, well-tolerated,
      highly rewarding complementary behavioral intervention for enhancing quality of
      life (QOL) as well as fitness among individuals with chronic and even terminal
      illnesses. However, relatively few studies have examined the feasibility and
      potential health benefits of supervised, structured exercise programs for
      sedentary women with primary breast cancer. Forty women over the age of 45 with
      primary breast cancer participated in a course of group exercise training (GET)
      delivered in a structured format three times per week for 16 weeks. GET
      emphasizes physical activities that promote aerobic fitness, strength, and
      flexibility. Assessments of fitness/vigor and QOL were conducted prior to,
      during, and upon completion of the program. Results demonstrated that GET was
      feasible, safe, and well-tolerated. Moreover, the participants experienced
      significant health benefits over the course of the intervention in multiple
      dimensions of fitness/vigor (aerobic capacity, strength, flexibility) as well as
      QOL (increased positive affect, decreased distress, enhanced well-being, and
      improved functioning). Discussion highlights the need for inclusion of physical
      activity programs in comprehensive, complementary treatment regimes for breast
      cancer patients.

PMID- 12228880
TI  - Statistical issues in the assessment of the evidence for an interaction between
      factors in epilepsy trials.
AB  - We examine the common clinical belief that there is an interaction between
      epilepsy type and the two standard anti-epileptic drugs, valproate and
      carbamazepine, using data from several randomized clinical trials. Epilepsy type
      is not always easy to define, and three possible reclassifications are
      investigated to see whether misclassification of epilepsy type within the trials
      has potentially masked such an interaction. Regression modelling is employed to
      investigate whether heterogeneity between trial results can be explained by
      patient factors. Our work suggests that uncertainty in epilepsy type
      classification should be recognized in future studies. We also generate the
      hypothesis that the interaction of drug effect with age may reflect the perceived
      interaction with epilepsy type. We suggest that in any context where
      misclassification is likely, it is worth considering the use of an explicit
      'unclassified' group, and investigating whether additional covariates can answer
      the substantive question.

PMID- 12228881
TI  - Fisher information matrix for non-linear mixed-effects models: evaluation and
      application for optimal design of enoxaparin population pharmacokinetics.
AB  - We address the problem of the choice and the evaluation of designs in population
      pharmacokinetic studies that use non-linear mixed-effects models. Criteria, based
      on the Fisher information matrix, have been developed to optimize designs and
      adapted to such models. We optimize designs under different constraints and
      evaluate them for a population pharmacokinetics study, within a new phase III
      trial of enoxaparin, a low molecular weight heparin. To do this, we approximate
      the expression of the Fisher information matrix for non-linear mixed-effects
      models including the residual error variance as a parameter to be estimated. We
      use the Fedorov-Wynn algorithm to minimize the inverse of the determinant of this
      matrix as required by the D-optimality criterion. Two optimal designs, as well as
      a design defined by pharmacologists, are evaluated by the simulation of 30
      replicated data sets with NONMEM; all designs involve 220 patients with four
      measurements per patient. We also evaluate the relevance of the standard errors
      of estimation given from the Fisher information matrix by comparison with those
      given by NONMEM. The three designs provide more precise population parameter
      estimates; the optimal design gives the best precision and offers a simple
      clinical implementation. The expected standard errors given by the information
      matrix are close to those obtained by NONMEM on the simulation. Moreover, the
      proposed criterion of D-optimality appears to be a good measure to compare
      designs for population studies.

PMID- 12228882
TI  - A graphical method for exploring heterogeneity in meta-analyses: application to a
      meta-analysis of 65 trials.
AB  - Heterogeneity can be a major component of meta-analyses and by virtue of that
      fact warrants investigation. Classic analysis methods, such as meta-regression,
      are used to explore the sources of heterogeneity. However, it may be difficult to
      apply such a method in complex cases or in the absence of an a priori hypothesis.
      This paper presents a graphical method to identify trials, groups of trials or
      groups of patients that are sources of heterogeneity. The contribution of these
      trials to the overall result can also be evaluated with this method. Each trial
      is represented by a dot on a 2D graph. The X-axis represents the contribution of
      the trial to the overall Cochran Q-test for heterogeneity. The Y-axis represents
      the influence of the trial, defined as the standardized squared difference
      between the treatment effects estimated with and without the trial. This approach
      has been applied to data from the Meta-Analysis of Chemotherapy in Head and Neck
      Cancer (MACH-NC) comprising 10,850 patients in 65 randomized trials. The
      graphical method allowed us to identify trials that contributed considerably to
      the overall heterogeneity and had a strong influence on the overall result. It
      also provided useful information for the interpretation of heterogeneity in this
      meta-analysis. The proposed graphical method identifies trials that account for
      most of the heterogeneity without having to explore all possible sources of
      heterogeneity by subgroup analyses. This method can also be applied to identify
      types of patients that explain heterogeneity in the treatment effect.

PMID- 12228883
TI  - Estimating disease prevalence in the absence of a gold standard.
AB  - When estimating disease prevalence, it is not uncommon to have data from
      conditionally dependent diagnostic tests. In such a situation, the estimation of
      prevalence is difficult if none of the tests is considered to be a gold standard.
      In this paper we develop a Bayesian approach to estimating disease prevalence
      based on the results of two diagnostic tests, allowing for the possibility that
      the tests are conditionally dependent, but not conditioning on any particular
      dependence structure. This involves the construction of four models with various
      forms of conditional dependence and uses Bayesian model averaging, enabled by
      reversible jump MCMC, to obtain an overall estimate of the prevalence. This
      methodology is demonstrated using a study on the prevalence of Strongyloides
      infection.

PMID- 12228885
TI  - Graphical models for multivariate time series from intensive care monitoring.
AB  - Nowadays physicians are confronted with high-dimensional data generated by
      clinical information systems. The proper extraction and interpretation of the
      information contained in such massive data sets, which are often observed with
      high sampling frequencies, can hardly be done by experience only. This yields new
      perspectives of data recording and also sets a new challenge for statistical
      methodology. Recently graphical models have been developed for analysing the
      partial correlations between the components of multivariate time series. We apply
      this technique to the haemodynamic system of critically ill patients monitored in
      intensive care. In this way we can appraise the practical value of the new
      procedure by re-identifying known associations within the haemodynamic system.
      From separate analyses for different pathophysiological states we can even
      conclude that distinct clinical states are characterized by distinct partial
      correlation structures. Hence, this technique seems useful for automatic
      statistical analysis of high-dimensional physiological time series and it can
      provide new insights into physiological mechanisms. Moreover, we can use it to
      achieve an adequate dimension reduction of the variables needed for online
      monitoring at the bedside.

PMID- 12228884
TI  - Survival curve estimation with partial non-random exposure information.
AB  - The objective of this paper is to estimate survival curves for two different
      exposure groups when the exposure group is not known for all observations, and
      the data is subject to left truncation and right censoring. The situation we
      consider is when the probability that the exposure group is missing may depend on
      whether the observation is censored or uncensored, in which case the exposure is
      not missing at random. The problem was motivated by a study of Alzheimer's
      disease to estimate the distribution of ages at diagnosis for individuals with
      and without an apolipoprotein E4 allele (the exposure group). Genotyping for this
      risk factor was incomplete and performed more frequently on the cases of
      Alzheimer's disease (the uncensored observations) than the censored observations.
      The survival curves are estimated in discrete time using an EM algorithm. A
      bootstrapping procedure is proposed that guarantees each bootstrap sample has the
      same proportion of observations with missing exposure. A simulation is performed
      to evaluate the bias of the estimators and to investigate design and efficiency
      issues. The methods are applied to the Alzheimer's disease study.

PMID- 12228886
TI  - Hierarchical statistical modelling of influenza epidemic dynamics in space and
      time.
AB  - An infectious disease typically spreads via contact between infected and
      susceptible individuals. Since the small-scale movements and contacts between
      people are generally not recorded, available data regarding infectious disease
      are often aggregations in space and time, yielding small-area counts of the
      number infected during successive, regular time intervals. In this paper, we
      develop a spatially descriptive, temporally dynamic hierarchical model to be
      fitted to such data. Disease counts are viewed as a realization from an
      underlying multivariate autoregressive process, where the relative risk of
      infection incorporates the space-time dynamic. We take a Bayesian approach, using
      Markov chain Monte Carlo to compute posterior estimates of all parameters of
      interest. We apply the methodology to an influenza epidemic in Scotland during
      the years 1989-1990.

PMID- 12228887
TI  - Goodness-of-fit processes for logistic regression: simulation results.
AB  - In this paper we use simulations to compare the performance of new goodness-of
      fit tests based on weighted statistical processes to three currently available
      tests: the Hosmer-Lemeshow decile-of-risk test; the Pearson chi-square, and the
      unweighted sum-of-squares tests. The simulations demonstrate that all tests have
      the correct size. The power for all tests to detect lack-of-fit due to an omitted
      quadratic term with a sample of size 100 is close to or exceeds 50 per cent to
      detect moderate departures from linearity and is over 90 per cent for these same
      alternatives for sample size 500. All tests have low power with sample size 100
      to detect lack-of-fit due to an omitted interaction between a dichotomous and
      continuous covariate, while the power exceeds 80 per cent to detect extreme
      interaction with a sample size of 500. The power is low to detect any alternative
      link function with sample size 100 and for most alternative links for sample size
      500. Only in the case of sample size 500 and an extremely asymmetric link
      function is the power over 80 per cent. The results from these simulations show
      that no single test, new or current, performs best in detecting lack-of-fit due
      to an omitted covariate or incorrect link function. However, one of the new
      weighted tests has power comparable to other tests in all settings simulated and
      had the highest power in the difficult case of an omitted interaction term. We
      illustrate the tests within the context of a model for factors associated with
      abstinence from drug use in a randomized trial of residential treatment
      programmes. We conclude the paper with a summary and specific recommendations for
      practice.

PMID- 12228888
TI  - Intensive short courses in biostatistics for fellows and physicians.
AB  - At both of our universities we teach (with colleagues) introductory courses in
      statistics for fellows and physicians. We do not expect that those taking these
      courses will be able to do their own statistical work, but rather the intention
      is for them to 'learn the language' and to facilitate future collaboration. Basic
      principles of study design are introduced in the courses, as well as some of the
      most common statistical procedures. We will discuss the factors (what works and
      what does not) that may contribute to a successful course, a comparison to other
      courses, and our self-evaluation strategy. Finally, we will cover the financial
      arrangements that we have made when teaching these courses.

PMID- 12228889
TI  - Competing designs for phase I clinical trials: a review.
AB  - Phase I clinical trials are typically small, uncontrolled studies designed to
      determine a maximum tolerated dose of a drug which will be used in further
      testing. Two divergent schools have developed in designing phase I clinical
      trials. The first defines the maximum tolerated dose as a statistic computed from
      data, and hence it is identified, rather than estimated. The second defines the
      maximum tolerated dose as a parameter of a monotonic dose-response curve, and
      hence is estimated. We review techniques from both philosophies. The goal is to
      present these methods in a single package, to compare them from philosophical and
      statistical grounds, to hopefully clear up some common misconceptions, and to
      make a few recommendations. This paper is not a review of simulation studies of
      these designs, nor does it present any new simulations comparing these designs.

PMID- 12228891
TI  - A preliminary evaluation of the differences in the glycosylation of alpha-1-acid
      glycoprotein between individual liver diseases.
AB  - During the acute phase response (APR) to tissue injury or infection, the liver is
      responsible for the level of mediators such as cytokines required at the site of
      inflammation and providing the essential components for wound healing and tissue
      repair. Additionally there are substantial alterations in the expression of
      plasma proteins of hepatic origin such as alpha-1-acid glycoprotein (AGP). The
      APR also results in alterations to the branching, sialylation and fucosylation of
      the oligosaccharide chains of AGP. This study investigated whether liver damage
      could be correlated with changes in AGP glycosylation in groups of patients with
      various liver diseases (alcoholic liver disease, hepatitis B, hepatitis C,
      cirrhosis). Hyperfucosylation occurred in all cases of liver disease, although
      the hepatitis B and C samples showed a more significant increase in comparison
      with the others. Additionally N-acetylgalactosamine (GalNAc) was detected in the
      majority of the hepatitis C samples, which was unexpected since this
      monosaccharide is not a usual component of the N-linked oligosaccharide chains.
      It was also determined by concanavalin (con) A chromatography that there is a
      shift towards the increased branching of the oligosaccharide chains in
      inflammatory liver diseases compared to normal serum.

PMID- 12228892
TI  - 5-Alpha- and 5-beta-2-deoxyintegristerone A, a 5-alpha and 5-beta isomer pair of
      ecdysteroids isolated from the Silene genus.
AB  - 5-Alpha-2-deoxyintegristerone A and 5-beta-2-deoxyintegristerone A were isolated
      from the aerial parts of Silene italica ssp. nemoralis (Waldst. and Kit.) Nyman
      using a specific combination of absorption column chromatography, preparative
      thin-layer chromatography and preparative HPLC. Both normal-phase and reversed
      phase modes of HPLC were employed for isolation. Structural elucidation of 5
      alpha-2-deoxyintegristerone A was completed by X-ray diffraction. Both 5-alpha-2
      deoxyintegristerone A and 5-beta-2-deoxyintegristerone A were firstly isolated
      from this plant. We propose that 5-alpha-2-deoxyintegristerone A is not an
      artifact but an integral part of the ecdysteroid spectrum of Silene italica ssp.
      nemoralis (Waldst. and Kit.) Nyman.

PMID- 12228893
TI  - A high-performance liquid chromatography method using ultraviolet detection for
      the quantitation of flavopiridol from human plasma.
AB  - Flavopiridol is an inhibitor of cyclin-dependent kinase, a key regulator of cell
      cycle, and is currently under clinical trials. We developed and validated an HPLC
      assay method for the quantitation of flavopiridol in human plasma samples. The
      sample preparation consisted of protein precipitation with acetonitrile.
      Separation was accomplished on a C(18) column and a C(18) precolumn insert
      utilizing a gradient profile consisting of ammonium acetate and methanol.
      Ultraviolet detection was set at 268 nm for flavopiridol and 323 nm for
      umbelliferone, the internal standard. The method was validated over flavopiridol
      concentration range of 0.025-3.0 microg/mL using 250 microL of plasma. The assay
      was linear over this concentration range with a coefficient of variation less
      than 10% for inter- and intra-assay. The retention times were around 6.2 min for
      umbelliferone and 9.8 min for flavopiridol. The recoveries of flavopiridol and
      umbelliferone were 88.6 +/- 1.0% and 97.1 +/- 3.7%, respectively. This method is
      suitable for quantifying flavopiridol in plasma samples and further
      characterizing the clinical pharmacology of this compound.

PMID- 12228894
TI  - Determination of lamivudine/stavudine/efavirenz in human serum using liquid
      chromatography/electrospray tandem mass spectrometry with ionization polarity
      switch.
AB  - A high-performance liquid chromatography/tandem mass spectrometry (LC-MS-MS)
      method with ionization polarity switch was developed and validated in human serum
      for the determination of a lamivudine (3TC)/stavudine (d4T)/efavirenz combination
      HIV therapy. Solid phase extraction (SPE) was used to extract these anti-HIV
      drugs and internal standard aprobarbital. A gradient mobile phase consisting of
      acetonitrile and 20 mM ammonium acetate buffer with pH adjusted to 4.5 using
      glacial acetic acid was utilized to separate these drugs on a hexylsilane column
      (150 x 2.0 mm i.d.). The total run time between injections was 18 min. The
      precursor and major product ions of these drugs were monitored on a triple
      quadrupole mass spectrometer in the multiple reactions monitoring (MRM) mode.
      Ionization polarity was switched in the middle of the LC run allowing these anti
      HIV drugs with different physicochemical properties to be detected
      simultaneously. The effect of ion suppression from human serum was studied and no
      interference with the analysis was noted. The method was validated over the range
      of 1.1-540 ng/mL for 3TC, 12.5-6228 ng/mL for d4T and 1.0-519 ng/mL for
      efavirenz. The method was shown to be accurate, with intra-day and inter-day
      accuracy less than 14.0% and precise, with intra-day and inter-day precision less
      than 13.1%. The extraction recoveries of all analytes were higher than 90%.

PMID- 12228895
TI  - Analysis of reaction products of cocaine and hydrogen peroxide by high
      performance liquid chromatography/mass spectrometry.
AB  - The change of chemical structure of cocaine in the presence of hydrogen peroxide,
      a main component of hair dye and decolorant treatments, was studied. High
      performance liquid chromatography/mass spectrometry (LC/MS) was used for the
      separation and identification of cocaine derivatives. After a mixture of cocaine
      and hydrogen peroxide solutions was incubated at 39 degrees C (this temperature
      is commonly used when the hair is treated with hair dye or decolorant) for 24 h,
      six reaction products were detected by LC/MS. Two of them were ecgonine methyl
      ester and benzoylecgonine, which are metabolites of cocaine. The other reaction
      products were assumed to be ortho-, meta- and para-hydroxycocaines and
      dihydroxycocaine, in each of which the benzene ring was hydroxylated by the
      reaction. These five reaction products (except for dihydroxycocaine) were found
      immediately after mixing cocaine and hydrogen peroxide. Therefore, the above
      reaction products might be present in the hair of cocaine users that had treated
      their hair with hair dye or decolorant.

PMID- 12228896
TI  - In vitro metabolism of a novel phosphodiesterase-5 inhibitor DA-8159 in rat liver
      preparations using liquid chromatography/electrospray mass spectrometry.
AB  - The in vitro metabolism of a new erectogenic, DA-8159, has been studied by LC
      with UV detection and on-line LC-electrospray mass spectrometry using rat hepatic
      microsomal incubation and rat liver perfusion. Both rat liver microsomal
      incubation of DA-8159 in the presence of NADPH and single-pass liver perfusion of
      DA-8159 resulted in the formation of three metabolites (M1-3). M1 was tentatively
      identified as hydroxy-DA-8159. M2 and M3 were identified as N-demethyl-DA-8159
      and 5-(2-propyloxy-5-aminosulphonylphenyl)-1-methyl-3-propyl-1,6-dihydro-7H
      pyrazolo(4,3-d)pyrimidin-7-one (DA-8164), respectively, on the basis of LC-MS/MS
      analysis with authentic standards. Rat CYP2D1 was a major isozyme for the
      formation of hydroxy-DA-8159 and N-demethyl-DA-8159. CYP2C12 and CYP1A1 catalysed
      the oxidation of DA-8159 to DA-8164.

PMID- 12228897
TI  - Rapid determination of anastrozole in plasma by gas chromatography with electron
      capture detection and its application to an oral pharmacokinetic study in healthy
      volunteers.
AB  - A rapid, sensitive and accurate capillary gas chromatographic assay with (63)Ni
      electron capture detection was developed for the determination of anastrozole in
      human plasma. It comprises a one-step liquid-liquid extraction procedure and gas
      chromatography on a capillary column using constant oven temperature. This method
      has been applied to the oral pharmacokinetic study of anastrozole in healthy
      Chinese male volunteers. Pharmacokinetic parameters of two anastrozole
      preparations were evaluated after single, oral administrations to 18 subjects at
      a dose of 1 mg in a single-blind cross-over trial. Plasma anastrozole
      concentration-time profiles were best described by a two-compartment model. After
      oral administrations of imported and domestic anastrozole tablets, the t(max) and
      C(max) were 1.52 +/- 1.04 h and 8.75 +/- 3.03 ng/mL for the former, and 1.43 +/-
      1.12 h and 9.44 +/- 3.59 ng/mL for the latter; the elimination half-life was 46.0
      +/- 25.2 h vs 41.2 +/- 8.8 h, and the area under the curve (AUC) was 423 +/- 114
      ng h/mL vs 444 +/- 157 ng h/mL. The result indicates that the two products are
      bioequivalent.

PMID- 12228898
TI  - Development of a new assay for the screening of hypochlorous acid scavengers
      based on reversed-phase high-performance liquid chromatography.
AB  - A new assay for the screening of hypochlorite/hypochlorous acid (XOCl)
      scavengers, based on the reversed-phase high performance liquid chromatographic
      analysis of human serum albumin (HSA, 0.2% in 100 mM sodium phosphate, pH 7),
      before and after oxidation by XOCl (1.6 mM), was developed. XOCl induced a
      significant decrease of the area under the chromatographic peak of HSA at 280 nm
      due to the oxidation of the aromatic amino acids tryptophan and tyrosine, as
      suggested by the literature and by the chromatographic analyses and the
      electrochemical study performed here. The assay was validated by testing known
      XOCl scavengers such as ascorbic acid, cysteine, glutathione, S-methylglutathione
      and alpha-lipoic acid and other antioxidants such as carnosine and chlorogenic
      acid, which inhibited the oxidation of HSA. Quantitative activities were
      calculated using an original formula based on the changes of the area of the
      albumin peak. Electrochemical data collected here in a homogeneous medium showed
      that the anodic potentials of the antioxidants tested are less positive (ascorbic
      acid, chlorogenic acid and cysteine) or similar (alpha-lipoic acid) compared with
      those of the aromatic residues (tryptophan and tyrosine) of HSA oxidized by XOCl.
      However, as expected, carnosine, glutathione and S-methylglutathione were
      inactive at a glassy-carbon, gold or platinum electrode.

PMID- 12228899
TI  - A preliminary evaluation of the functional significance of alpha-1-acid
      glycoprotein glycosylation on wound healing.
AB  - The laying down of collagen and fibrous tissue is a key process in wound healing,
      however excessive collagen (and glycoprotein) deposition causes hypertrophic and
      keloid scars, eg after burns. Collagen synthesis is increased in these scars
      compared with normal healing, as is collagenase activity, which controls the
      degradation pathway of collagen. The processes of wound healing are inextricably
      linked to those of the acute-phase response (APR): alpha-1-acid glycoprotein
      (AGP), a plasma glycoprotein that undergoes both an increase in concentration and
      an alteration in its glycosylation pattern during the APR. This study determined
      that AGP isolated from the plasma of burns patients was of an increased
      concentration and altered glycosylation pattern compared with normal plasma and
      was capable of directly interacting with type I collagen. It also had a profound
      effect on both collagen fibril formation and collagenase activity, to a degree
      dependent upon the percentage body surface area burned. Additionally, the results
      obtained provided the basis for predicting the formation of hypertrophic scars.

PMID- 12228900
TI  - Semi-micro liquid chromatography of aromatic amino acid metabolites using
      isocratic elution and column switching.
AB  - The concentrations of catecholamine-related compounds in body fluids reflect
      sympathetic nerve functions. Measuring the enzyme activity of these metabolic
      pathways will improve diagnosis since a variety of symptoms are reported. An
      isocratic elution system with two column switching valves was developed using
      three types of semi-micro columns for fast chromatographic analysis of
      catecholamine related compounds. Columns are a pentyl-bonded phase, 50 x 2.1 mm
      i.d., a phenylhexyl-bonded phase, 100 x 2.1 mm i.d. and an octadecyl-bonded
      phase, 100 x 2.1 mm i.d. The separation of 20 standard compounds was achieved
      within 25 min using reversed-phase ion-pair liquid chromatography with an
      electrochemical detector. This new system was applied for analysis of
      catecholamine-related compounds in pig brain, since pigs are a widely used animal
      model for transgenic manipulation of neural genes, and MHPG (or VMA), DOPAC,
      DOPA, NE, EP, DA, 5HTP and 5HIAA were quantified.

PMID- 12228902
TI  - Modern treatment of childhood hepatoblastoma: what do clinicians and pathologists
      have to say to each other?

PMID- 12228903
TI  - Hepatoblastoma: assessment of criteria for histologic classification.
AB  - BACKGROUND: Comparison of outcomes in different clinicopathologic studies of
      hepatoblastoma requires reproducible histologic classification. This review
      examines the diagnostic criteria employed by different pathologists for the
      classification of subtypes of hepatoblastoma and identifies specific problem
      areas. PROCEDURE: A selected review of published literature is provided. RESULTS:
      Published studies demonstrate that uniform criteria have not been applied in the
      classification of hepatoblastoma. These discrepancies hinder attempts to compare
      outcome data from different studies. Sampling error and potential treatment
      effects further complicate analysis of the published literature on the
      relationship between morphologic classification and outcome. CONCLUSIONS:
      Standardized criteria are essential to allow reproducible histologic
      classification of hepatoblastoma. There is significant variation in diagnostic
      criteria used to define the major subtypes of hepatoblastoma in published
      studies. Additional potential problems are identified in sampling methods and
      treatment effects.

PMID- 12228904
TI  - Chemotherapy for suspected hepatoblastoma without efforts at surgical resection
      is a bad practice.
AB  - BACKGROUND: US and European practices differ with respect to treating
      hepatoblastoma (HB). Should chemotherapy be given prior to resection in all
      cases, and even without biopsy confirmation (SIOPEL)? PROCEDURE AND RESULTS: US
      data indicate that 40% of HBs are primarily resectable with no operative
      mortality and that those with pure fetal histology and low mitotic rate do not
      require toxic chemotherapy. They also suggest that those with a significant
      fraction of small undifferentiated cells do not respond to otherwise effective
      chemotherapy. Both US and European studies report a significant error rate in the
      clinical and imaging diagnosis of HB. CONCLUSIONS: Although only 6.5% of
      confirmed HBs fall into categories that would be managed differently by US
      standards, there is no justification for denying those patients a more
      appropriate treatment nor should the 6-10% of cases that are misdiagnosed as HB
      be treated incorrectly.

PMID- 12228905
TI  - Hepatoblastoma with cholangioblastic features ('cholangioblastic hepatoblastoma')
      and other liver tumors with bimodal differentiation in young patients.
AB  - In a subset of hepatoblastomas, differentiation of neoplastic cells can proceed
      along a pathway resulting in cholangiocyte-like cells. These cells either occur
      as single, immunohistochemically detectable elements, or form incomplete and
      complete duct-like profiles in continuation with embryonal, fetal or
      macrotrabecular hepatoblastoma components. As a working formulation it is
      proposed to employ the term, hepatoblastoma with cholangioblastic features (or
      'cholangioblastic' hepatoblastoma), to denote such lesions. This bimodal
      differentiation presents itself in other rare tumors in the form of complex
      arrays of duct-like cells encircling nests of neoplastic hepatocyte lineage
      cells, in some way mimicking a ductal plate. A possible pathogenetic pathway is
      suggested, i.e., uni- or bipotential neoplastic progenitors switch into either of
      the two lineages.

PMID- 12228906
TI  - Pediatric liver tumors and hepatic ontogenesis: common and distinctive pathways.
AB  - Several types of pediatric liver tumors exhibit structural features apparently
      reflecting processes which normally occur during hepatic ontogenesis: some
      hepatoblastomas mimic distinct phases of hepatogenesis, including the formation
      of mesenchymal structures closely associated with immature epithelia, and there
      are tumors almost exclusively consisting of complex mesenchymal patterns. Current
      classifications of hepatoblastomas refer to the identification of more or less
      mature (differentiated) single or mixed components seen in histologic
      preparations. These do not, however, attempt to integrate ontogenic pathways, in
      contrast for example, to nephroblastoma and associated lesions, where such a view
      has proved to be highly fruitful. Based on the fact that an enormous amount of
      knowledge has recently been accumulated regarding hepatic ontogenesis, time may
      have come to look at these tumors with a new eye. In what follows, we aim at
      trying to analyze distinct features of pediatric hepatic tumors (except vascular
      tumors) within the background of ontogenesis. Some key steps of hepatogenesis and
      the regulatory factors involved may, in the future, deliver an armamentarium to
      search for novel molecular mechanisms involved in tumorigenic pathways.

PMID- 12228907
TI  - Stem-like cells in hepatoblastoma.
AB  - BACKGROUND: The principles of tumor biology suggest that hepatoblastoma is
      derived from a pluripotent stem cell. Our studies were undertaken to investigate
      this tumor for the presence of cells with morphologic and immunophenotypic
      features of the oval cells of rodents that are thought to be closely related to
      hepatic stem cells. PROCEDURE: Hepatoblastomas of various subtypes were
      investigated by electron microscopy and immunoelectron microscopy with antibodies
      against cytokeratin 7, in the liver a marker of biliary differentiation, and
      albumin, a marker of hepatocytic differentiation. Immunohistochemical
      investigations were performed with the antibodies OV-1 and OV-6, which recognize
      antigens associated with oval cells. RESULTS: OV-1 stained scattered cells in
      seven of 12 tumors investigated and OV-6 in nine. Small epithelial cells (SEC)
      with the ultrastructural features of the oval cells were found by electron
      microscopy. They were characterized by small size (7-18 microm), often an oval
      shape, tonofilament bundles, and tight junctions or desmosome-like junctions. SEC
      were found in small numbers in areas of fetal differentiation and in moderate
      numbers in areas of embryonal differentiation. In small cell hepatoblastoma,
      nearly all the tumor cells exhibited SEC-like features. Immunoelectron microscopy
      revealed coexpression of cytokeratin 7 and albumin by SEC. CONCLUSIONS: SEC with
      ultrastructural and immunophenotypic features exhibited by oval cells, i.e.,
      hepatic stem-like cells, are found in hepatoblastoma. Their numbers vary with the
      differing degrees of differentiation seen in the various subtypes. The findings
      further support the hypothesis that hepatoblastoma is derived from a pluripotent
      stem cell.

PMID- 12228908
TI  - Hepatoblastoma and low birth weight: a trend or chance observation?
AB  - BACKGROUND: Several reports have suggested an association between prematurity and
      hepatoblastoma (HB). PROCEDURE: Data were collected by questionnaires from 105
      children with HB enrolled in a Children's Cancer Group (CCG) study. RESULTS:
      Observed over expected rates were increased about 2- and 15+-fold for prematurity
      (<37 weeks at birth) and low birth weight (<1,000 g) respectively. Similar data
      were derived from a later CCG study of 36 HB children. CONCLUSIONS: Early reports
      of a possible association between prematurity and HB have been confirmed.

PMID- 12228909
TI  - Transitional liver cell tumors (TLCT) in older children and adolescents: a novel
      group of aggressive hepatic tumors expressing beta-catenin.
AB  - BACKGROUND: We encountered on seven malignant hepatocellular tumors developing in
      older children and adolescents. RESULTS: These tumors exhibit an unusual
      phenotype with respect to clinical presentation, histopathology,
      immunohistochemistry, and treatment response. As a working hypothesis, we suggest
      that these apparently novel, unusual, and aggressive tumors occurring in older
      children and adolescents may form a transition in the putative developmental
      pathway of hepatocarcinogenesis. CONCLUSION: We therefore propose the term,
      transitional liver cell tumors (TLCT), to denote these lesions.

PMID- 12228910
TI  - Adult type vs. Childhood hepatocellular carcinoma--are they the same or different
      lesions? Biology, natural history, prognosis, and treatment.
AB  - BACKGROUND: Differences in the biology, natural history, and treatment results of
      hepatocellular carcinoma (HCC) in children and adults were sought based on the
      literature and experience resulting from SIOPEL 1 trial. PROCEDURE: In the
      SIOPEL1 study, 40 children with HCC were registered from January 1990 to February
      1994. Outcome was analyzed in 39. In most cases, disease was advanced at
      diagnosis: 31% had metastases and 39% had extrahepatic tumor extension and/or
      vascular invasion. More than 50% of patients had multifocal tumors; 39% of tumors
      were associated with hepatic cirrhosis. All, but two patients, received
      preoperative chemotherapy (PLADO--cisplatin and doxorubicin). Outcome, response
      to treatment, and prognostic factors were analyzed using the SAS statistical
      package. RESULTS: Overall survival (OS) at 5 years is 28% and EFS is 17% at
      median follow-up of 75 months (49-90). Partial response to chemotherapy was
      observed in 18 of 37 cases evaluated (49%). Complete tumor resection was achieved
      in 14 of the 39 patients (36%). Twenty (51%) never became operable. Multifocality
      of the tumor, presence of metastases, and PRETEXT grouping adversely influenced
      OS. A large number of "de novo" HCC cases, fairly high response rate to
      preoperative chemotherapy (49%) and 54% survival after complete resection
      constitute a significant difference in comparison with adult HCC series.
      CONCLUSIONS: Survival for pediatric HCC patients is below 30%. Radical tumor
      resection remains the only chance for survival. New multi-center prospective
      studies in children with HCC are required to better results and to allow further
      study of differences between adult and pediatric HCC should they exist.

PMID- 12228911
TI  - Hemangioma of the liver in children: proliferating vascular tumor or congenital
      vascular malformation?
AB  - BACKGROUND: Hepatic vascular tumors (HVT) are the most common benign liver tumors
      present in infancy and childhood commonly associated with high output cardiac
      failure. Pediatric HVT usually are divided into infantile hemangioendothelioma
      (IHE), cavernous hemangioma (HC), and arteriovenous malformations (AVM). The aim
      of this study was to analyze clinical and histologic features of pediatric HVT in
      relation to treatment strategies. PROCEDURE: During last 12 years, 17 children
      have been treated because of HVT. The diagnosis of HVT was established in all on
      the basis of clinical and imaging data. A retrospective analysis of clinical
      records and histopathology divided 17 into: Group 1, neonates; and Group 2,
      infants and older children. RESULTS: Radiologic imaging revealed the vascular
      nature of the tumors in all patients. All nine from Group 1 were symptomatic from
      AVMs and seven were operated upon. Only one of eight children from Group 2
      presented symptoms of AVM requiring surgery; four of five in this group had
      surgery because of the risk of malignancy. Within Group 1, a mixture of
      proliferating IHE with microscopic features of AVM was found in most. In three
      neonates with HVT immunologic and clinical features of cytomegalovirus (CMV)
      hepatitis were noted. In two Group 2 patients, pure HC was present and in
      another, the diagnosis of angiosarcoma was established after biopsy of a
      peritoneal metastasis. CONCLUSIONS: HVT in children demonstrate internal
      morphologic heterogeneity and an age-related behavior of the disease. We also
      confirm the proliferative nature of all hemangioendotheliomas (HEs) in children.
      Further studies on the tumorigenesis of these lesions are needed.

PMID- 12228912
TI  - Genetic alterations in hepatoblastoma and hepatocellular carcinoma: common and
      distinctive aspects.
AB  - Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are two different subtypes
      of primary tumors arising from liver parenchymal cells. These tumors differ by
      many histoclinical characteristics, and comparative analysis of genetic
      alterations in HB and HCC might provide some clues on the molecular oncogenic
      pathways leading to hepatocyte transformation. Recent outcomes have been provided
      by the assessment of global genetic changes in tumor cells, using conventional
      cytogenetic approaches, PCR-based microsatellite analysis and Comparative genomic
      Hybridization (CGH). Cytogenetic studies of HB, microsatellite analysis of HCC
      and recent CHG data have outlined common and distinctive characters between the
      two tumor types. HBs are characterized by a low number of chromosomal changes,
      consisting mainly of gains at chromosomes 1q, 2, 8q, 17q, and 20. By contrast,
      HCCs harbor multiple chromosomal abnormalities, predominantly losses, with
      increased chromosomal instability in tumors associated with hepatitis B virus
      infection. Common alterations in HB and HCC include gain of chromosomes 1q, 8q,
      and 17q, and loss of 4q. Another important common feature shared by the two tumor
      types is the frequent activation of Wnt/beta-catenin signaling by stabilizing
      mutations of beta-catenin. Immunohistochemical analysis of beta-catenin has
      demonstrated nuclear/cytoplasmic accumulation of the protein in most HBs and in
      more than one third of HCCs. Strikingly, beta-catenin mutations are associated
      with chromosomal stability in both tumor types. Together, these studies define
      different pathways in liver cell transformation, reflecting various developmental
      stages and multiple risk factors. A detailed understanding of the molecular hits
      underlying liver tumorigenesis, combined with clinicopathological parameters,
      will permit an accurate evaluation of major targets for prognostic and
      therapeutic intervention.

PMID- 12228913
TI  - Fluorescent in situ hybridization (FISH) reveals frequent and recurrent numerical
      and structural abnormalities in hepatoblastoma with no informative karyotype.
AB  - BACKGROUND: Hepatoblastoma (HB) is the most frequent malignant liver tumor in
      children. The few cytogenetic studies available indicate that HB is associated
      with recurring trisomies of chromosomes 2, 8, and 20; recurrent t(1;4) (q12;q34)
      has been reported in few cases. The abnormalities of chromosome 1q are relatively
      frequent and usually lead to overexpression of 1q material. A cluster of
      breakpoints is located at the level of bands 1q12 and 1q21. More work is needed
      to clarify their real incidence and prognostic significance. Cytogenetic analysis
      is limited by the requirement of suitable cells in metaphase. A different method
      that increases analysis sensitivity is fluorescent in situ hybridization (FISH).
      PROCEDURE: We studied 10 cases of HB with no informative karyotype (normal
      karyotype or no metaphases). FISH was performed by the standard method, using
      cytospins and imprints obtained from frozen or cytogenetic samples of direct
      cultures. Alpha-satellite probes for centromeric DNA were used for chromosomes 2,
      8, and 20 analysis; rearrangement of region 1q12-21 was detected with BAC
      (bacterial artificial chromosome) probe bA79E5. RESULTS: We detected at least one
      trisomic clone in 5/10 of these cases. Trisomy 20 was the most frequently
      detected abnormality, followed by trisomy of the chromosomes 2 and 8. Analysis of
      1q12 band revealed that the rearrangement of 1q usually is in pericentromeric
      heterochromatin, it was present in 5/10 of studied cases. CONCLUSION: FISH
      analysis is recommended in all cases of HB with no informative karyotype to gain
      more information regarding the frequent trisomies encountered and their
      significance.

PMID- 12228914
TI  - Discussion and epilogue.

PMID- 12228917
TI  - Surface plasmon resonance spectroscopy: an emerging tool for the study of peptide
      membrane interactions.
AB  - The interactions between peptides and membranes mediate a wide variety of
      biological processes, and characterization of the molecular details of these
      interactions is central to our understanding of cellular events such as protein
      trafficking, cellular signaling and ion-channel formation. A wide variety of
      biophysical techniques have been combined with the use of model membrane systems
      to study peptide-membrane interactions, and have provided important information
      on the relationship between membrane-active peptide structure and their
      biological function. However, what has generally not been reported is a detailed
      analysis of the affinity of peptide for different membrane systems, which has
      largely been due to the difficulty in obtaining this information. To address this
      issue, surface plasmon resonance (SPR) spectroscopy has recently been applied to
      the study of biomembrane-based systems using both planar mono- or bilayers or
      liposomes. This article provides an overview of these recent applications that
      demonstrate the potential of SPR to enhance our molecular understanding of
      membrane-mediated peptide function.

PMID- 12228919
TI  - Osteogenic growth peptide: from concept to drug design.
AB  - Recently, the osteogenic growth peptide (OGP) and its C-terminal pentapeptide H
      Tyr-Gly-Phe-Gly-Gly-OH [OGP(10-14)] have attracted considerable clinical interest
      as bone anabolic agents and hematopoietic stimulators. They are present in
      mammalian serum in micromolar concentrations, increase bone formation and
      trabecular bone density, and stimulate fracture healing when administered to mice
      and rats. In cultures of osteoblastic and other bone marrow stromal cells,
      derived from human and other mammalian species, OGP regulates proliferation,
      alkaline phosphatase activity and matrix mineralization via an
      autocrine/paracrine mechanism. In vivo it also regulates the expression of type I
      collagen and the receptor for basic fibroblast growth factor. In addition, OGP
      and OGP(10-14) enhance hematopoiesis, including the stimulation of bone marrow
      transplant engraftment and hematopoietic regeneration after ablative
      chemotherapy. Apparently, the hematopoietic effects of these peptides are
      secondary to their effect on the bone marrow stroma. Detailed structure-activity
      relationship study identified the side chains of Tyr(10) and Phe(12) as the
      principal pharmacophores for OGP-like activity. Recently, it has been
      demonstrated that several cyclostereoisomers of OGP(10-14), including the
      analogue retro-inverso (Gly-Gly-D-Phe-Gly-D-Tyr), share the full spectrum of OGP
      like bioactivities. Taken together, OGP represents an interesting case of a
      "housekeeping" peptide that plays an important role in osteogenesis and
      hematopoiesis, and interacts with its putative macromolecular target via distinct
      pharmacophores presented in a specific spatial organization.

PMID- 12228918
TI  - Matrix metalloproteinases and collagen catabolism.
AB  - The matrix metalloproteinase (MMP)/matrixin family has been implicated in both
      normal tissue remodeling and a variety of diseases associated with abnormal
      turnover of extracellular matrix components. The mechanism by which MMPs
      catabolize collagen (collagenolysis) is still largely unknown. Substrate
      flexibility, MMP active sites, and MMP exosites all contribute to collagen
      degradation. It has recently been demonstrated that the ability to cleave a
      triple helix (triple-helical peptidase activity) can be distinguished from the
      ability to cleave collagen (collagenolytic activity). This suggests that the
      ability to cleave a triple helix is not the limiting factor for collagenolytic
      activity-the ability to properly orient and potentially destabilize collagen is.
      For the MMP family, the catalytic domain can unwind and cleave a triple-helical
      structure, while the C-terminal hemopexin-like domain appears to be responsible
      for properly orienting collagen and destabilizing it to some degree. It is also
      possible that exosites within the catalytic and/or C-terminal hemopexin-like
      domain may exclude some MMPs from cleaving collagen. Overall, it appears that
      many proteases of distinct mechanisms possess triple-helical peptidase activity,
      and that convergent evolution led to a few proteases possessing collagenolytic
      activity. Proper orientation and distortion of the triple helix may be the key
      factor for collagenolysis.

PMID- 12228920
TI  - The synthesis and study of side-chain lactam-bridged peptides.
AB  - Side-chain lactam bridges linking amino acid residues that are spaced several
      residues apart in the linear sequence offer a convenient and flexible method for
      introducing conformational constraints into a peptide structure. The availability
      of a variety of selectively cleavable protecting groups for amines and carboxylic
      acids allows for several approaches to the synthesis of monocyclic, dicyclic, and
      bicyclic lactam-bridged peptides by solid-phase methods. Multicyclic structures
      are also accessible, but segment-condensation syntheses with solution-phase
      cyclizations are most likely to provide the best synthetic approach to these more
      complex constrained peptides. Lactam bridges linking (i, i + 3)-, (i, i + 4), and
      (i, i + 7)-spaced residue pairs have all proven useful for stabilization of alpha
      helices, and (i, i + 3)-linked residues have also been demonstrated to stabilize
      beta-turns. These structures are finding an increasing number of applications in
      protein biology, including studies of protein folding, protein aggregation,
      peptide ligand-receptor recognition, and the development of more potent peptide
      therapeutics. Defining the functional roles of the amphiphilic alpha-helices in
      medium-sized peptide hormones, and studying helix propagation from rigid, alpha
      helix initiating bicyclic peptides are among the most exciting developments
      currently underway in this field.

PMID- 12228922
TI  - Effect of cationic charge localization on DNA structure.
AB  - DNA is normally considered to be a stiff rod-like molecule, but proteins and
      small molecules, which either equilibrium bind to, or covalent bond with, DNA,
      can overcome the barrier(s) to non-linearity by changing the local hydrophobic
      and electrostatic environment at specific DNA sequences. The deformation of DNA
      by proteins has been shown to be a critical event in transcriptional regulation.
      In this review, we have focused on how the introduction of cationic charge, and
      its location, can affect DNA structure. To study the effect of charge, we have
      used DNA modified with 3-aminopropyl substitutions at the 5-position of
      deoxyuracil that mimic basic lysine-like sidechains, and which place the cationic
      charge in the major groove. Previous gel mobility studies with these sidechains
      have shown that they bend DNA. The location of the cationic sidechains and how
      they bend DNA is discussed.

PMID- 12228923
TI  - Antimetabolite incorporation into DNA: structural and thermodynamic basis for
      anticancer activity.
AB  - Antimetabolites are a class of effective anticancer drugs that structurally
      resemble naturally occurring biochemicals and interfere in essential biochemical
      processes. In this review, the recent literature describing investigations of the
      structural and thermodynamic basis for the anticancer activity of three
      antipyrimidines [1-beta-D-arabinofuranosyl cytidine (AraC). 2',2'-difluoro
      deoxycytidine (dFdC), and 5-fluoro-2'-deoxyuridine (FdUrd)] is summarized. Our
      laboratory, and others, have shown that misincorporation of any of these three
      antipyrimidines into DNA perturbs the structure and decreases the stability of
      duplex DNA. These data are useful for rationalizing the effects of antipyrimidine
      misincorporation on the activities of proteins required for DNA replication and
      repair such as DNA topoisomerase 1 and DNA polymerases. The studies completed to
      date and summarized in this review demonstrate the utility of investigations into
      the structure-function relationships between antipyrimidine-substituted DNA
      complexed with DNA-modifying proteins for the purpose of understanding the basis
      for effective antipyrimidine cancer chemotherapy and the future design of novel
      anticancer drugs.

PMID- 12228924
TI  - Thermal stabilization of the DNA duplex by adducts of aflatoxin B1.
AB  - The trans-8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B(1) cationic guanine N7
      adduct of aflatoxin B(1) thermally stabilizes the DNA duplex, as reflected in
      increased T(m) values upon adduction. The magnitude of the increased T(m) value
      is characteristically 2-3 degrees C. The major rotamer of the neutral guanine N7
      adduct trans-8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)
      9-hydroxy aflatoxin B(1) (the FAPY major adduct) exhibits a 15 degrees C increase
      in T(m) in 5'-d(CTAT(FAPY)GATTCA)-3'-5'-d(TGAATCATAG)-3'. Site-specific
      mutagenesis experiments reveal the FAPY major adduct induces G-->T mutations in
      Escherichia coli at a frequency six times higher than that of the cationic adduct
      (Smela, M. E.; Hamm, M. L.; Henderson, P. T.; Harris, C. M.; Harris, T. M.;
      Essigmann, J. M. Proc Natl Acad Sci USA, 99, 6655-6660). Thus, the FAPY major
      lesion may account substantially for the genotoxicity of AFB(1). Structural
      studies for cationic and FAPY adducts of aflatoxin B(1) suggest both adducts
      intercalate above the 5'-face of the modified deoxyguanosine and that in each
      instance the aflatoxin moiety spans the DNA helix. Intercalation of the aflatoxin
      moiety, accompanied by favorable stacking with the neighboring base pairs, is
      thought to account for the increased thermal stability of the aflatoxin cationic
      guanine N7 and the FAPY major adducts. However, the structural basis for the
      large increase in thermal stability of the FAPY major adduct in comparison to the
      cationic guanine N7 adduct of aflatoxin B(1) is not well understood. In light of
      the site-specific mutagenesis studies, it is of considerable interest. For both
      adducts, the intercalation structures are similar, although improved stacking
      with neighboring base pairs is observed for the FAPY major adduct. In addition,
      the presence of the formamido group in the aflatoxin B(1) FAPY major adduct may
      enhance duplex stability, perhaps via intrastrand sequence-specific hydrogen
      bonding interactions within the duplex.

PMID- 12228925
TI  - Thermodynamic and structural factors in the removal of bulky DNA adducts by the
      nucleotide excision repair machinery.
AB  - The function of the human nucleotide excision repair (NER) apparatus is to remove
      bulky adducts from damaged DNA. In an effort to gain insights into the molecular
      mechanisms involved in the recognition and excision of bulky lesions, we
      investigated a series of site specifically modified oligonucleotides containing
      single, well-defined polycyclic aromatic hydrocarbon (PAH) diol epoxide-adenine
      adducts. Covalent adducts derived from the bay region PAH, benzo[a]pyrene, are
      removed by human NER enzymes in vitro. In contrast, the stereochemically
      analogous N(6)-dA adducts derived from the topologically different fjord region
      PAH, benzo[c]phenanthrene, are resistant to repair. The evasion of DNA repair may
      play a role in the observed higher tumorigenicity of the fjord region PAH diol
      epoxides. We are elucidating the structural and thermodynamic features of these
      adducts that may underlie their marked distinction in biologic function,
      employing high-resolution nuclear magnetic resonance studies, measurements of
      thermal stabilities of the PAH diol epoxide-modified oligonucleotide duplexes,
      and molecular dynamics simulations with free energy calculations. Our combined
      findings suggest that differences in the thermodynamic properties and thermal
      stabilities are associated with differences in distortions to the DNA induced by
      the lesions. These structural effects correlate with the differential NER
      susceptibilities and stem from the intrinsically distinct shapes of the fjord and
      bay region PAH diol epoxide-N(6)-adenine adducts.

PMID- 12228926
TI  - Importance of minor groove functional groups for the stability of DNA duplexes.
AB  - Eight oligonucleotide duplexes have been prepared with four pairs of selected
      complementary pairs of native/analogue heterocyclic bases incorporated at a
      selected test site. The base pairs vary in the nature of their functionality in
      the minor groove. Each pair has a minor groove purine amino group present or
      absent, and correspondingly has a minor grove pyrimidine carbonyl present or
      absent. Loss of duplex stability is most notable when the minor groove pyrimidine
      carbonyl is absent although in other respects normal Watson-Crick hydrogen
      bonding is maintained in these sequences. These differences in stability are
      discussed in terms of possible variations in minor groove hydration.

PMID- 12228929
TI  - Talking with Rob Bush, president of Orchard Software Corporation. Interview by C.
      Anne Pontius.

PMID- 12228927
TI  - DNA oligonucleotide duplexes containing intramolecular platinated cross-links:
      energetics, hydration, sequence, and ionic effects.
AB  - The anticancer activity of cisplatin arises from its ability to bind covalently
      to DNA, forming primarily intrastrand cross-links to adjacent purine residues;
      the most common adducts involve d(GpG) (65%) and d(ApG) (25%) intrastrand cross
      links. The incorporation of these platinum adducts in a B-DNA helix induces local
      distortions, causing bending and unwinding of the DNA. In this work, we used
      temperature-dependent UV spectroscopy to investigate the unfolding
      thermodynamics, and associated ionic effects, of two sets of DNA decamer duplexes
      containing either cis-[Pt(NH(3))(2)[d(GpG]] or cis-[Pt(NH(3))(2) [d(ApG]] cross
      links, and their corresponding unmodified duplexes. The platinated duplexes are
      less stable and unfold with lower T(M)s (and Delta G degrees s) in enthalpy
      driven reactions, which indicates a loss of favorable base-pair stacking
      interactions. The folding thermodynamics and hydration effects for the first set
      of decamers containing the d(GpG) cross-link was investigated by a combination of
      titration calorimetry, density, and ultrasound techniques. The hydration
      parameters showed an uptake of structural water by the platinated duplex and a
      release of electrostricted water by the control duplex. Relative to the
      unmodified duplex, the folding of the platinated duplex at 20 degrees C yielded a
      positive Delta Delta G degrees term [and positive Delta Delta H-Delta(T Delta S)
      compensation] and a negative differential volume change. The opposite signs of
      the Delta Delta G degrees and Delta Delta V terms confirmed its uptake of
      structural water. Further, solvent-accessible surface areas calculations for a
      similar pair of dodecamer duplexes indicated that the modified duplex has a 503
      oeA(2) higher polar and nonpolar surface area that is exposed to the solvent.
      Therefore, the incorporation of a platinum adduct in duplex DNA disrupts
      favorable base-pair stacking interactions, yielding a greater exposure of
      aromatic bases to the solvent, which in turn immobilizes structural water. The
      overall results correlate nicely with the results reported in the available
      structural data of nuclear magnetic resonance solution studies.

PMID- 12228930
TI  - Defining the business associate provision of HIPAA.

PMID- 12228931
TI  - Laboratories clear first hurdle with House-passed Medicare bill.

PMID- 12228932
TI  - The Pap smear: a victim of its own success?

PMID- 12228933
TI  - 2002 GHA Community Leadership Award. Walton Rehabilitation Hospital focused on
      helping people with physical disabilities.

PMID- 12228934
TI  - Former nonprofits owe $12 million in intermediate sanctions case.

PMID- 12228935
TI  - As insurance crisis worsens, GHA testifies before Senate Committee.

PMID- 12228936
TI  - Cultural crossroads. How nurses, health care meet the challenge.

PMID- 12228937
TI  - ANA establishes National Nurses Response Team for disaster response.

PMID- 12228938
TI  - Tough decisions: helping patients families choose long-term care.

PMID- 12228943
TI  - Concurrent validity of questionnaire and performance-based disability
      measurements in patients with chronic nonspecific low back pain.
AB  - This study aimed to investigate the concurrent validity of two approaches to
      disability measurement in patients with chronic nonspecific low back pain (CLBP).
      It was hypothesized that if both are measuring the same construct, the
      instruments would lead to similar disability results and would correlate strongly
      (r > 0.75). The study compared the results of self-reported and performance-based
      measures of disability in 64 consecutive patients with CLBP. Participants mean
      age was 38.0 years, the mean duration of the current episode of back pain 9.9
      months, and 90% were off work due to CLBP. The self-report measures used were:
      the Roland Disability Questionnaire (Roland); the Oswestry Disability
      Questionnaire (Oswestry); and the Quebec Back Pain Disability Questionnaire
      (Quebec). Performance was measured using the Isernhagen Work Systems Functional
      Capacity Evaluation (FCE). The mean scores from the self-report measure are as
      follows: Roland 13.5 (scale 0-24), Oswestry 28.2 (scale 0-100), Quebec 37.8
      (scale 0-100) consistent with moderate to severe disability. In contrast the
      results from the performance-based measures suggested that the subjects should be
      able to work at a physical intensity level of moderate to heavy. Little to
      moderate correlation was observed between the self-report and performance-based
      measures (Spearman rank correlations: Roland-FCE (-0.20), p > 0.05; Oswestry-FCE
      (-0.52), p < 0.01; Quebec-FCE (-0.50), p < 0.01). Results are interpreted to
      suggest that both performance-based and self-report measures of disability should
      be used in order to obtain a comprehensive picture of the disability in patients
      with CLBP.

PMID- 12228944
TI  - Occupational upper extremity conditions: a detailed analysis of work-related
      outcomes.
AB  - While work-related upper extremity conditions (WRUECs) cause almost 25% of lost
      time cases in the US, little is known about their long-term occupational
      consequences. A self-report survey was mailed to New Hampshire workers reporting
      a WRUEC one year prior to the study. Of the 72 (52%) valid respondents, 60% had
      lost > or = 1 week of work and 90% had returned to work. Almost 70% reported
      acute injury onset, and 26% had experienced a recurrence of their WRUEC. Both
      gradual-onset injuries and recurrences had worse outcomes. Recurrence was related
      to shorter job tenure, lower job satisfaction, and less satisfaction with medical
      care and insurer responses. Results imply that a single measure is insufficient
      to assess occupational outcomes subsequent to a WRUEC. The importance of
      secondary prevention was highlighted. There is a need for focus on gradual-onset
      injuries, as well as those acute-onset injuries with risk for recurrence.

PMID- 12228945
TI  - Is disability underreported following work injury?
AB  - Existing national data may underreport the full burden of occupational injuries
      and illnesses. This study sought to provide more complete reporting and to assess
      disability that persisted following return to work. Workers (n = 205) with a
      musculoskeletal injury resulting in 5 or more days of lost time or restricted
      duty were recruited from three employers. Data on work status and functional
      limitations were derived from multiple sources including administrative records,
      medical records, and patient interviews at baseline and 6 months. Results
      indicate that many workers reported continuing difficulties functioning at work
      following return to full duty. Measures of health-related quality of life
      improved over 6 months, but bodily pain and physical functioning scores remained
      lower than expected based on national averages. Sixteen percent of workers were
      reinjured within a year following initial injury. Following return to work, many
      workers experienced reinjury or reported persistent limitations in function 6
      months following injury. Based on study findings the conclusion is drawn that
      OSHA logs may provide accurate measures of initial episodes of time loss from
      work but may under-represent the full magnitude of lost time following work
      injury.

PMID- 12228946
TI  - Self-reported reduced productivity due to musculoskeletal symptoms: associations
      with workplace and individual factors among white-collar computer users.
AB  - The aim was to assess whether self-reported reduced productivity occurred in
      computer users due to musculoskeletal symptoms and the association to workplace,
      symptom, and individual factors. The study group consisted of 1283 computer users
      from different occupations, of whom 498 were men and 785 were women. Reduced
      productivity was self-assessed by two questions addressing if and how much
      productivity was reduced the previous month due to musculoskeletal symptoms.
      There were 63 women (8.0%) and 42 men (8.4%) of the total study group who
      reported reduced productivity due to musculoskeletal symptoms. The mean magnitude
      of the reduction was 15% for women and 13% for men. This outcome was weakly
      associated with computer mouse position and task and symptom persistence for both
      men and women. For women, work demands, computer problems, and being
      divorced/separated were also associated with reduced productivity. Although
      limited by problems of subjectivity of self-report and the possibility of
      significant underreporting, these results suggest that a variety of interventions
      may serve to decrease the impact of musculoskeletal disorders in the workplace.

PMID- 12228947
TI  - Transitions in self-reported musculoskeletal pain and interference with
      activities among newspaper workers.
AB  - Active surveillance of symptoms and disability due to musculoskeletal disorders
      (MSD) in working populations can map individual transitions in symptom intensity
      or disability level. Using repeat surveys, this study examined if aetiological
      risk factors for new symptoms or disability, measured by interference with
      activities, were similar to prognostic risk factors for subsequent outcomes of
      symptoms and disability. This paper reports on 379 Toronto newspaper workers who
      completed questionnaires in 1996 and 1997. Questions on pain/discomfort during
      the last year, episode frequency and duration formed the basis for constructing
      three mutually exclusive symptom levels: noncases (Level 1); mild cases (Level
      2); and more severe or frequent pain cases (Level 3). A similar construction of
      overall interference levels was based on the frequency with which musculoskeletal
      pain/discomfort interfered with daily, recreational, social and family
      activities, or ability to do one's job during the previous 12 months. The last
      was also examined as work interference alone. Levels of symptoms were cross
      tabulated by overall and work interference at the two time points and Markov
      models of transitions between states were formulated. Results indicate that
      period prevalence of symptoms and overall interference increased between phases,
      though only significantly for symptoms (Levels 2 and 3, 65.7-70.7%, p = 0.04),
      while work interference was unchanged (17.9-17.0%). Equivalent proportions of
      workers improved as worsened in symptoms (21.1 and 22.4%, respectively), overall
      interference (16.7 and 17.8%), and work interference (7.4 and 6.6%). The only
      significant predictor for those without work interference at time one was job
      tenure, which was protective against work interference (Odds Ratio (OR) 1.06, 95%
      Confidence Interval (CI) 1.01-1.12). Among those who had more severe/frequent
      symptoms at time one, lack of improvement over time was predicted by longer job
      tenure (OR = 0.92 per year, CI: 0.87-0.97), greater psychological demands of work
      (OR = 0.65 per point, CI: 0.51-0.84) and marginally by greater upper extremity
      disability score. At time one, women with work interference were more likely to
      have persistent interference at time two (OR = 7.22, CI: 1.57-33.20). Suggestive
      findings included opposite effects of social support at work: reduced risk of
      development of new symptoms but increased risk of persistence at the highest
      symptom level.

PMID- 12228948
TI  - A social psychology approach to measuring vocational rehabilitation intervention
      effectiveness.
AB  - It is rare for rehabilitation researchers to report substantial relationships
      between functional capacity and vocational rehabilitation achievements. The
      reason for this is that there are many other factors that also impact on the
      return-to-work outcomes people achieve. A solution to the problem of having to
      take into consideration the effects of multiple factors when evaluating
      intervention effectiveness is to focus more directly on cognitions and behaviors
      that have been theoretically and empirically linked with a satisfactory return to
      work. The aim of this paper is to explore and describe a measure of
      rehabilitation effectiveness based in cognitive-behavioral theory. Rather than
      the measurement of employment per se, the described measure is focused on the
      efforts individuals make in relation to achieving their desired outcome. To test
      the effectiveness, acceptability, and utility of the approach, the measure was
      trialed with 170 people with a spinal cord injury. This preliminary work has
      revealed that participants found the measure acceptable and gave detailed
      responses in regards to: their satisfaction with their vocational status; what it
      is they would prefer to be doing; and what it is that they are doing to achieve
      their aims. Study findings suggest that while the approach is likely to require
      further development, focusing on process variables holds promise as an evaluation
      approach when assessing the success of vocational rehabilitation intervention
      effectiveness.

PMID- 12228949
TI  - Helping clinicians in work disability prevention: the work disability diagnosis
      interview.
AB  - Recent evidence has demonstrated that disability from musculoskeletal disorders
      is a multifactorial problem that is not only due to workers' characteristics but
      also closely related to environmental factors, such as the workplace, the health
      care system, the compensation system, and the interactions among all stakeholders
      regarding the disability problem. The Work Disability Diagnosis Interview (WoDDI)
      was developed following a systematic method in order to help clinicians detect
      possible disability prognostic factors in subacute or chronic musculoskeletal
      pain patients. A structured literature review, followed by expert input and a
      second round of revisions after 4-year's usage led to the current version. The
      WoDDI is composed of open-ended questions on physical, psychosocial,
      occupational, and administrative factors, collated into an interview form used at
      the first encounter with the disabled worker. It enables clinicians to develop a
      rehabilitation plan and focus on disability resolution in patients absent from
      work due to a musculoskeletal disorder. Initial application demonstrated a high
      prevalence of sociodemographic, work-related, and psychosocial factors that may
      contribute to prolonged work absence.

PMID- 12228950
TI  - Comparing severity of impairment for different permanent upper extremity
      musculoskeletal injuries.
AB  - The labor market impact of upper extremity musculoskeletal injuries that result
      in permanent disability was estimated using data from the State of California.
      Administrative data on disability evaluations and resulting ratings was matched
      to data on the earnings of over 7000 injured workers. Using these data, labor
      market experience pre- and postinjury was tracked. Each injured worker was
      matched to a set of control workers who worked at the same firm, had the same
      tenure at the firm, and earned the same income at the time of injury. By
      comparing the injured and uninjured workers, lost earnings and the impact of
      injury on return to work was estimated. Evidence of considerable lost earnings
      resulting from injury was found. The results are compared to "disability ratings"
      that are used to set compensation under California's workers' compensation
      program. The disability rating was also found to predict poorly differences
      across upper extremity injuries in losses. In particular, those with shoulder
      injuries have larger losses than those with elbow or wrist injuries, despite
      receiving the same disability ratings.

PMID- 12228951
TI  - Inadequately controlled asthma. Patients do not understand their treatment plans.

PMID- 12228952
TI  - Metronidazole and pregnancy.

PMID- 12228953
TI  - St John's wort as treatment for depression.

PMID- 12228954
TI  - Confirming proper use of medication: more than one way.

PMID- 12228955
TI  - Treating family members: call your doctor in the morning.

PMID- 12228956
TI  - Education on abortion in medical schools appalling.

PMID- 12228957
TI  - Accidental patient. A doctor takes a different view.

PMID- 12228958
TI  - Update on motherisk updates. Seven years of questions and answers.
AB  - QUESTION: Every month I read the Motherisk Updates in your journal and find them
      very helpful in counseling my patients on exposures during pregnancy and
      breastfeeding. I was wondering: what are the most common questions you receive
      from family physicians? ANSWER: Since the Motherisk Update began, we have
      received an increasing number of inquiries from family physicians across Canada.
      Most questions are about drug exposures. The three classes of drugs asked about
      most often are antidepressants, antiepileptics, and antihistamines.

PMID- 12228959
TI  - Practice tips. Improving interpersonal skills. One method of dealing with
      confrontation.

PMID- 12228960
TI  - Chronic cough. Three most common causes.
AB  - OBJECTIVE: To describe an approach to diagnosis and treatment of patients with
      chronic cough. QUALIITY OF  EVIDENCE: MEDLINE was search for reports of studies
      comducted between 1970 and 2000 on chronic cough and its epidemiology, natural
      history, diagnois, and theraphy. Articles were further selected based on clinical
      relevance and design. Most articles reviewed were epidemiology cohort and case
      studies and reviews. MAIN MESSAGE: Chronic cough, a commom ailment amoung adults,
      is often a diagnostic challenge. Most cases of chronic cough are associated with
      postnasal drip syndrome (PNDS), asthma, gastroesphageal reflux disease (GERD), or
      some combination of these. Initial investigation should include chest radiography
      to ruke out more ominous causes of chronic cough. Examinations and trials of
      treatment can diagnose PNDS, asthma, and GERD. Combination treatments are often
      necessary for managing chronic cough. CONCLUSION: The most common causes of
      chronic cough are PNDS, asthma, GERD, or some combination of these. A systematic
      approach to diagnosis and treatment is effective for most cases of chronic.
      cough.

PMID- 12228961
TI  - Case report: cough variant asthma.

PMID- 12228962
TI  - Hemochromatosis. Common genes, uncommon illness?
AB  - OBJECTIVE: To increase family physicians' awareness of the prevalence of
      hemochromatosis and to suggest strategies for diagnosis and management of
      hemochromatosis with the goal of decreasing the development of associated life
      threatening conditions. QUALITY OF EVIDENCE: A MEDLINE search from January 1966
      to January 2002 using the MeSH term hemochromatosis/therapy found no randomized
      controlled trials. A further search from January 1990 to January 2002, using the
      heading hemochromatosis and subheadings diagnosis, epidemiology, genetics, and
      therapy, found articles with level II evidence (case-control and cross-sectional
      studies) and level III evidence (descriptive studies and reports from expert
      committees). Articles were selected based on clinical relevance. MAIN MESSAGE:
      Hemochromatosis is the most common hereditary condition in populations of
      Northern European descent, affecting three to five people per thousand. Many of
      these people remain undiagnosed with this condition. The iron overload associated
      with hemochromatosis can lead to serious, life-threatening conditions, such as
      diabetes, hepatic cirrhosis, primary liver cancer, and cardiomyopathy. Family
      physicians can screen patients they suspect are at risk of hemochromatosis with
      simple indirect serum iron measurements (transferrin saturation and serum
      ferritin) and with widely available genetic tests (C282Y and H63D). Studies of
      families can help uncover further cases of hemochromatosis; population screening
      is currently under study. CONCLUSION: Family physicians can facilitate early
      diagnosis of hemochromatosis by maintaining a high index of suspicion in patients
      with early signs or symptoms or in high-risk groups, and screening these patients
      for hemochromatosis.

PMID- 12228964
TI  - Personalized action plans. How to help your patients manage their asthma.

PMID- 12228963
TI  - Performance assessment. Family physicians in Montreal meet the mark!
AB  - OBJECTIVE: To assess the clinical performance of a representative non-volunteer
      sample of family physicians in metropolitan Montreal, Que. DESIGN: Assessment of
      clinical performance was based on inspection visits to offices, peer review of
      medical records, and chart-stimulated recall interviews. The procedure was the
      one usually followed by the Professional Inspection Committee of the College des
      medecins du Quebec. SETTING: Family physicians' practices in metropolitan
      Montreal. PARTICIPANTS: One hundred randomly selected family physicians.
      INTERVENTIONS: For each physician, 30 randomly chosen patient charts with data on
      three to five previous visits were reviewed using explicit criteria and a
      standard scale using global scores from 1 to 5 (unacceptable to excellent). MAIN
      OUTCOME MEASURES: Scores were assigned for office practices; record keeping;
      number of continuing medical education (CME) activities; and quality of clinical
      performance assessed in terms of investigation plan, diagnostic accuracy,
      treatment plan, and relevance of care. RESULTS: Overall performance was judged to
      be good to excellent for 98% of physicians in their private practices; for 90% of
      physicians concerning CME activities; for 94% of physicians concerning their
      clinical performance in terms of quality of care; and for 75% of physicians as to
      record keeping. There was a link between record keeping and quality of care as
      well as between the number of CME activities and quality of care. CONCLUSION: The
      overall clinical performance of family physicians in the greater Montreal region
      is excellent.

PMID- 12228965
TI  - Hypothesis: the research page. Integrating population health into social ecology.
      Role of family medicine researchers.

PMID- 12228966
TI  - [Surgical treatment of the hepatic hilum].

PMID- 12228968
TI  - [Reoperations in thyroid surgery].
AB  - The Authors examine etiology, incidence and hazards related to reoperation in
      thyroid surgery either for benign either for malignant pathology. The Authors
      present, then, 26 secondary operations performed in the Unit of Surgical
      Pathology of the Department of Surgical Sciences Chieti University: 15 for
      benign, 11 for malignant pathology. In the cases of thyroid malignant pathology,
      in 2 patients (operated in different hospitals) there was a parenchimatous
      recurrence, in 2 patients a lymphnodal recurrence. In all the patients a total
      thyroidectomy was performed, in one patient associated with lymphadenectomy. In
      the patients with lymphadenomatous recurrence a functional laterocervical
      lymphadenectomy was performed.

PMID- 12228967
TI  - [Breast carcinoma in accessory gland: a case report].
AB  - The Authors we report the case of a 50 year old woman with accessory breast
      cancer in the thoracic region. The examination revealed a mass of 1 cm diameter
      and a tumorectomy showed a ectopic breast with an intraductal carcinoma. Nodal
      dissection, chemo-, radio- and hormonal therapy there performed. The follow up
      didn't show a relapse of breast carcinoma after 5 years.

PMID- 12228969
TI  - [Pancreatic anastomotic fistula after pancreaticoduodenectomy: incidence,
      significance and treatment].
AB  - The Authors reviewed the complications, and outcomes in a consecutives series of
      97 patients undergoing pancreaticoduodenectomy. The clinical leak rate in this
      series was 21.8%. There was a difference in the pancreatic leak rate in those
      patients who underwent pancreatic ductal closure or end to end pancreaticojejunal
      invagination compared with end to side pancreaticojejunal anastomosis. The
      postoperative complication rate was 41.8% and the most common complications were
      pancreatic fistula. 9 deaths occurred in hospital or within 30 days from
      operation. Univariate and multivariate analysis revealed that operative
      technique, the pathological status of the pancreatic remnant, and mayor
      complications were the significant risk factors for the development of pancreatic
      anastomotic leak. In the 2000s pancreatic leak remains a potentially lethal
      problem. After pancreaticoduodenectomy, pancreatic remnant management by end to
      side pancreaticojejunostomy appeared safe in low-risk patients. Morbidity was
      greatest after pancreatic duct closure without anastomosis.

PMID- 12228970
TI  - [Parietal implantation after thoracoscopic surgery: a case report].
AB  - The Authors report the case of a patient who underwent video-thoracoscopic
      resection of a solitary pulmonary metastasis. She presented, after about two
      years, a local relapse (implantation) in the trocar site. Pathogenesis and
      surgical therapeutic problems are discussed as well.

PMID- 12228971
TI  - [Our experience in the diagnosis and treatment of diffuse peritonitis].
AB  - Acute diffuse peritonitis is still an unpredictable occurrence that hinders
      patient's survival and is a severe challenge for the surgeon regarding diagnosis
      and management. The Authors report their experience on 94 cases of acute diffuse
      peritonitis due to different causes observed during a period of 10 years.
      Surgical treatment was mainly based on severity of clinica data and general
      conditions of the patients. Overall mortality was 6.3%. Modern diagnostic
      techniques, proper usage of antibiotics and accurate timing of surgical procedure
      constitute the main factors for un update management of peritonitis.

PMID- 12228972
TI  - [Esophageal non-variceal hemorrhage: a clinical and epidemiological study].
AB  - Aim of this study was to evaluate the incidence of esophageal bleeding in a group
      of 3741 consecutive patients with acute non variceal upper gastrointestinal
      hemorrhage observed between January 1990 and January 1999 in the First Division
      of General Surgery--University of Verona. In 627 patients (16.8%) the source of
      bleeding was exclusively esophageal; and the most frequent causes of esophageal
      bleeding were reflux esopagitis (408 cases) and Mallory Weiss syndrome (185
      cases). At emergency endoscopy, reflux esophagitis was actively bleeding in 83
      cases (20.3%) and these patients presented a significantly higher frequency of
      cirrhosis and severe esophagitis; moreover a higher percentage of patients with
      bleeding esophagitis have had recent surgery and/or were hospitalized in an
      intensive care unit. No death directly related to the bleeding were observed,
      while ten patients deceased from other causes during the hospitalization. In more
      than half of the 185 patients affected by Mallory-Weiss syndrome a hiatal hernia
      was described and 69 (37.3%) were alcoholics with associated cirrhosis in 25
      cases. In more than 70% of the cases the bleeding from a mucosal tear followed a
      vomit episode and the lesions were localized at the gastroesophageal junction.
      Endoscopic sclerotherapy was performed in 89 patients with active bleeding and
      hemostasis was initially obtained in all patients; rebleeding occurred in 6
      patients (6.7%) who needed a further endoscopic treatment. No patients died
      during hospitalization. Other causes of esophageal bleeding observed were:
      Candida esophagitis (19 cases), esophageal malignancy (11 cases), benign polyps
      (2 cases), angiodysplasia (one case) and one case of aorto-esophageal fistula.

PMID- 12228973
TI  - [Rectorrhagia caused by lipoma of the hepatic flexure of the colon. A case report
      and review of the literature].
AB  - The Authors report a case of intestinal bleeding due to lipoma of the epatic
      flexure. Lipomas are the commonest mesenchymal benign tumors that can be found in
      the colon and are second as frequence only to the adenomatous polyps. They are
      most frequent in the right colon and shown an opposite distribution in comparison
      with adenocarcinomas and adenomatous polyps. When tumor size is greater than 3
      cm, lipomas become symptomatic. Radiological and endoscopic investigations
      provide orientative elements for diagnosis. In lipomas less than 2 cm in diameter
      an endoscopic treatment is feasible.

PMID- 12228974
TI  - [Neurinoma of the brachial plexus: 2 case reports].
AB  - Neurinomas, also referred to as neurilemmomas and schwannomas, are rare benign
      tumours of the peripheral nerves. A small percentage of these lesions arise from
      the brachial plexus. The Authors report two cases of schwannoma arising from the
      brachial plexus. Such lesions, usually asymptomatic, may cause sensitivity
      alterations or, less frequently, motor deficits in the involved arm. Tumour
      enucleation, avoiding damage to any of the nervous fascicles, is the treatment of
      choice.

PMID- 12228975
TI  - [Rare pathology of the breast: adenoma of the nipple].
AB  - Adenoma of the nipple is a benign pathology which histologically interests the
      epithelium of the galactophorous ducts. This pathology looks like Paget's disease
      both macroscopically and microscopically, therefore an exact differential
      histologic diagnosis is needed with the breast's carcinoma to undertake the most
      timely surgical therapy.

PMID- 12228976
TI  - [Parietal metastasis in laparoscopic surgery of colorectal carcinoma].
AB  - The role of videosurgery in the treatment of gastrointestinal cancers is still
      controversial. However port-site metastases, reported with high rate (0.6-21%)
      have reduced the enthusiasm and still represent object of research. Port-site
      metastases pathophysiology is not yet clear. However in the last years the
      incidence is decreased at a percentage less than 2% and similar to that reported
      after traditional surgery (0.6-5.3%) due to a patient selection and a better
      videosurgical technique. Implant for direct contact, pneumoperitoneum, gas
      utilized, trocar positioning and relative tessutal trauma, visceral manipulation,
      frequent instrumental reintroduction represent the main pathophysiologic factors
      involved. Pneumoperitoneum produces an increase of the abdominal pressure with
      turbulent flows and the CO2 (stimulating of neoplastic cells growth?) transports
      neoplastic cells at the port site. However metastases occurs only when an elevate
      cellular concentration is present "gas less" videosurgery is not free from this
      complication but with a lower incidence. "Chimney effect", due to the leakage of
      gas or fluid containing aerosol neoplastic cells at port site, represents another
      important factor. In accord with such studies employing alternative gas (Helium)
      reduces the implant of neoplastic cells. Port site parietal trauma produces
      fibrin deposites that represents a substratum for cellular implant, growth and
      protection against immunitary host defense. Wound ischemia induces a macrophagic
      activity decrease. In view of these concepts the surgeon must respect some
      mandatory principles in the videosurgical approach to neoplastic diseases. Safety
      parietal trocar fixation avoiding gas or fluid port site leakage such as
      abdominal desuffling only through trocars in site are mandatory. Instrumental
      cleaning with cytoxic solution (Betadine)--neoplastic cells are isolated from
      instrumental lavage liquid--such as as irrigation and sterilization (5 FU) of
      porte site are very important rules. Wound incision--never too small--must be
      accurately sutured. During operation cutting through or handling tumor are
      contraindicated, especially when the neoplasm involves serosa. Surgical specimens
      must be extracted in bags absolutely through parietal protection system. High
      vascular ligature represents another technical rule to respect in every case like
      in traditional surgery.

PMID- 12228977
TI  - [Regional anesthesia in quadrantectomy and sentinel lymph node].
AB  - After a brief mention about the mammary surgery, the Authors discuss the
      availability of regional anesthesia for quadrantectomy and "sentinel" node or
      axillary dissection.

PMID- 12228978
TI  - [Use of totally implantable venous system in cancer patients. Surgical technique
      and initial clinical experience].
AB  - The experience with a totally implanted venous system (TIVS) in 27 cancer
      patients (15 males and 12 women) is reviewed, stressing simplicity of the cut
      down technique, which was successfully performed in 92.7% of patients. The
      common: est complications are described; port infection (7.4%), subclavian vein
      thrombosis (3.7%), and cutaneous necrosis (3.7%) at the port level. It is
      concluded that TIVS is a useful device for prolonged drugs administration and the
      cut down technique is indicated especially in the outpatients setting.

PMID- 12228979
TI  - Kinematic control of walking.
AB  - The planar law of inter-segmental co-ordination we described may emerge from the
      coupling of neural oscillators between each other and with limb mechanical
      oscillators. Muscle contraction intervenes at variable times to re-excite the
      intrinsic oscillations of the system when energy is lost. The hypothesis that a
      law of coordinative control results from a minimal active tuning of the passive
      inertial and viscoelastic coupling among limb segments is congruent with the idea
      that movement has evolved according to minimum energy criteria (1, 8). It is
      known that multi-segment motion of mammals locomotion is controlled by a network
      of coupled oscillators (CPGs, see 18, 33, 37). Flexible combination of unit
      oscillators gives rise to different forms of locomotion. Inter-oscillator
      coupling can be modified by changing the synaptic strength (or polarity) of the
      relative spinal connections. As a result, unit oscillators can be coupled in
      phase, out of phase, or with a variable phase, giving rise to different
      behaviors, such as speed increments or reversal of gait direction (from forward
      to backward). Supra-spinal centers may drive or modulate functional sets of
      coordinating interneurons to generate different walking modes (or gaits).
      Although it is often assumed that CPGs control patterns of muscle activity, an
      equally plausible hypothesis is that they control patterns of limb segment motion
      instead (22). According to this kinematic view, each unit oscillator would
      directly control a limb segment, alternately generating forward and backward
      oscillations of the segment. Inter-segmental coordination would be achieved by
      coupling unit oscillators with a variable phase. Inter-segmental kinematic phase
      plays the role of global control variable previously postulated for the network
      of central oscillators. In fact, inter-segmental phase shifts systematically with
      increasing speed both in man (4) and cat (38). Because this phase-shift is
      correlated with the net mechanical power output over a gait cycle (3, 4), phase
      control could be used for limiting the overall energy expenditure with increasing
      speed (22). Adaptation to different walking conditions, such as changes in body
      posture, body weight unloading and backward walk, also involves inter-segmental
      phase tuning, as does the maturation of limb kinematics in toddlers.

PMID- 12228980
TI  - Limb movements generated by stimulating muscle, nerve and spinal cord.
AB  - We have compared the movements generated by stimulation of muscle, nerve, spinal
      roots and spinal cord in anesthetized, decerebrate and spinalized cats. Each
      method produced a full range of movements of the cat's hind limb in the sagittal
      plane against a spring load, except for stimulation of the roots. Stimulation of
      the dorsal roots produced movements that were mainly up and forward, whereas
      stimulation of the ventral roots produced complementary movements (down and
      backward). Results from stimulation in the intermediate areas of the spinal cord
      were compared to predictions of the "movement primitives" hypothesis. We could
      not confirm that the directions were independent of stimulus amplitude or the
      state of descending inputs. Pros and cons of stimulating at some sites were
      provisionally considered for the reliable control of limb movements with
      functional electrical stimulation (FES) in clinical conditions.

PMID- 12228981
TI  - Separation and estimation of muscle spindle and tension receptor populations by
      vibration of the biceps muscle in the frog.
AB  - Frog spinal cord reflex behaviors have been used to test the idea of spinal
      primitives. We have suggested a significant role for proprioception in regulation
      of primitives. However the in vivo behavior of spindle and golgi tendon receptors
      in frogs in response to vibration are not well described and the proportions of
      these proprioceptors are not established. In this study, we examine the
      selectivity of muscle vibration in the spinal frog. The aim of the study was (1)
      to examine how hindlimb muscle spindles and GTO receptors are activated by muscle
      vibration and (2) to estimate the relative numbers of GTO receptors and spindle
      afferents in a selected muscle, for comparison with the mammal. Single muscle
      afferents from the biceps muscle were identified in the dorsal roots. These were
      tested in response to biceps vibration, intramuscular stimulation and biceps
      nerve stimulation. Biceps units were categorized into two types: First, spindle
      afferents which had a high conduction velocity (approximately 20-30 m/s),
      responded reliably (were entrained 1:1) to muscle vibration, and exhibited
      distinct pauses to shortening muscle contractions. Second, golgi tendon organ
      afferents, which had a lower conduction velocity (approximately 10-20 m/s),
      responded less reliably to muscle vibration at physiologic muscle lengths, but
      responded more reliably at extended lengths or with background muscle
      contraction, and exhibited distinct bursts to shortening muscle contractions.
      Vibration responses of these units were tested with and without muscle
      curarization. Ensemble (suction electrode) recordings from the dorsal roots were
      used to provide rough estimates of the proportions of the two muscle afferent
      types.

PMID- 12228982
TI  - Development of path stereotypy in a single day in rats on a multiple-T maze.
AB  - Humans and animals trained on sequential reaction tasks show decreases in
      reaction time and increases in anticipatory movements even long after they have
      ceased to make errors. Humans show these changes even when they do not explicitly
      recognize that they performed a repeating sequence. We have developed a task
      which rats learn to perform error-free quickly, but in which they continue to
      show path-refinement on a single day. This task may enable the study of
      performance strategy changes occurring within a single day.

PMID- 12228983
TI  - An expert system for fault management assistance on a space sleep experiment.
AB  - The expert system, Principal Investigator-in-a-box, or [PI], was designed to
      assist astronauts or other operators in performing experiments outside their
      expertise. Currently, the software helps astronauts calibrate instruments for a
      Sleep and Respiration Experiment without contact with the investigator on the
      ground. It flew on the Space Shuttle missions STS-90 and STS-95. [PI] displays
      electrophysiological signals in real time, alerts astronauts via the indicator
      lights when a poor signal quality is detected, and advises astronauts how to
      restore good signal quality. Thirty subjects received training on the sleep
      instrumentation and the [PI] interface. A beneficial effects of [PI] and training
      reduced troubleshooting time. [PI] benefited subjects on the most difficult
      scenarios, even though its lights were not 100% accurate. Further, questionnaires
      showed that most subjects preferred monitoring waveforms with [PI] assistance
      rather than monitoring waveforms alone. This study addresses problems of complex
      troubleshooting and the extended time between training and execution that is
      common to many human operator situations on earth such as in power plant
      operation, and marine exploration.

PMID- 12228984
TI  - Dynamics and viewing distance dependence of eye movements during transient
      lateral motion.

PMID- 12228985
TI  - The vestibulo-ocular reflex and velocity storage in spinocerebellar ataxia 8.
AB  - The autosomal dominant spinocerebellar ataxias (SCAs) are a group of
      neurodegenerative diseases characterized by progressive instability of posture
      and gait, incoordination, ocular motor dysfunction, and dysarthria due to
      degeneration of cerebellar and brainstem neurons. Among the more than 20
      genetically distinct subtypes, SCA8 is one of several wherein clinical
      observations indicate that cerebellar dysfunction is primary, and there is little
      evidence for other CNS involvement. The aim of the present work was to study the
      decay of the horizontal vestibulo-ocular reflex (VOR) after a short period of
      constant acceleration to understand the pathophysiology of the VOR due to
      cerebellar Purkinje cell degeneration in SCA8. The VOR was recorded in patients
      with genetically defined SCA8 during rotation in the dark. Moderate to severely
      affected patients had a qualitatively intact VOR, but there were quantitative
      differences in the gain and dynamics compared to normal controls. During angular
      velocity ramp rotations, there was a reversal in the direction of the VOR that
      was more pronounced in SCA8 compared to controls. Modeling studies indicate that
      there are significant changes in the velocity storage network, including abnormal
      feedback of an eye position signal into the network that contributes to this
      reversal. These and other results will help to identify features that are
      diagnostic for SCA subtypes and provide new information about selective
      vulnerability of neurons controlling vestibular reflexes.

PMID- 12228986
TI  - Complex predictive eye pursuit in monkey: a model system for cerebellar studies
      of skilled movement.
AB  - Smooth pursuit eye movements provide a good model system for cerebellar studies
      of complex motor control in monkeys. First, the pursuit system exhibits
      predictive control along complex trajectories and this control improves with
      training. Second, the flocculus/paraflocculus region of the cerebellum appears to
      generate this control. Lesions impair pursuit and neural activity patterns are
      closely related to eye motion during complex pursuit. Importantly, neural
      responses lead eye motion during predictive pursuit and lag eye motion during non
      predictable target motions that require visual control. The idea that
      flocculus/paraflocculus predictive control is non-visual is also supported by a
      lack of correlation between neural activity and retinal image motion during
      pursuit. Third, biologically accurate neural network models of the
      flocculus/paraflocculus allow the exploration and testing of pursuit mechanisms.
      Our current model can generate predictive control without visual input in a
      manner that is compatible with the extensive experimental data available for this
      cerebellar system. Similar types of non-visual cerebellar control are likely to
      facilitate the wide range of other skilled movements that are observed.

PMID- 12228987
TI  - Plasticity in the visual system: role of neurotrophins and electrical activity.
AB  - We report recent results concerning the action of neurotrophins on the
      development and plasticity of the visual system of mammals and in particular of
      their visual cortex. It has been demonstrated that NGF prevents all the effects
      of monocular deprivation during the critical period. BDNF, that in part also
      prevents the effects of monocular deprivation, has the interesting additional
      property of accelerating the development of inhibitory processes. In transgenic
      mice overexpressing BDNF only in the cortex, the critical period for plasticity
      initiates a week earlier and presents a precocious closure. Visual acuity also
      develops much before than in normal animals. These phenomenological observations
      are paralleled by a precocious increase of inhibitory synapses and inhibitory
      currents in pyramidal neurons. LTP, tested by stimulation of the white matter,
      recording in layers 2 and 3 of the visual cortex, presents modifications
      correlated with the alterations observed in the critical period. Last we report
      the finding from in vitro and in vivo experiments that MAPkase (Erg 1 and 2) is
      the molecular chain of events driven both by light and neurotrophins, likely at
      the bases of the phenomena of plasticity observed during the critical period.

PMID- 12228988
TI  - How voltage-gated ion channels alter the functional properties of ganglion and
      amacrine cell dendrites.
AB  - The present study compares the structure and function of retinal ganglion and
      amacrine cell dendrites. Although a superficial similarity exists between
      amacrine and ganglion cell dendrites, a comparison between the branching pattern
      of the two cell types reveals differences which can only be appreciated at the
      microscopic level. Whereas decremental branching is found in ganglion cells, a
      form of non-decremental or "trunk branching" is observed in amacrine cell
      dendrites. Physiological differences are also observed in amacrine vs ganglion
      cells in which many amacrine cells generate dendritic impulses which can be
      readily distinguished from those of the soma, while separate dendritic impulses
      in ganglion cell dendrites have not been reported. Despite these differences,
      both amacrine and ganglion cell dendrites appear to contain voltage-gated ion
      channels, including TTX-sensitive sodium channels. One way to account for
      separate dendritic impulses in amacrine cells is to have a higher density of
      sodium channels and we generally find in modeling studies that a dendritic sodium
      channel density that is more than about 50% of that in the soma is required for
      excitatory, synaptic currents to give rise to local dendritic spike activity.
      Under these conditions, impulses can be generated in the dendrites and propagate
      for some distance along the dendritic tree. When the soma generates impulse
      activity in amacrine cells, it can activate, antidromically, the entire dendritic
      tree. Although ganglion cell dendrites do not appear to generate independent
      impulses, the presence of voltage-gated ion channels in these structures appears
      to be important for their function. Modeling studies demonstrate that when
      dendrites lack voltage-gated ion channels, impulse activity evoked by current
      applied to the cell body is generated at rates that are much higher than those
      observed physiologically. However, by placing ion channels in the dendrites at a
      reduced density compared to those of amacrine cells, the firing rate of ganglion
      cells becomes more physiological and the relationship between frequency and
      current (F/I relationship) can be precisely matched with physiological data.
      Recent studies have demonstrated the presence of T-type calcium channels in
      ganglion cells and our analysis suggests that they are found in higher density in
      the dendrites compared to the soma. This is the first voltage-gated ion channel
      which appears more localized to the dendrites than other cell copartments and
      this difference alone cries for an interpretation. The presence of a significant
      T-type calcium channel density in the dendrites can influence their integrative
      properties in several important ways. First, excitatory synaptic currents can be
      augmented by the activation of T-type calcium channels, although this is more
      likely to occur for transient rather than sustained synaptic currents because T
      type currents show strong inactivation properties. In addition, T-type calcium
      channels may serve to limit the electrical load which dendrites impose on the
      spike initiation process and thus enhance the speed with which impulses can be
      triggered by the impulse generation site. This role whill enhance the safety
      factor for impulses traveling in the orthograde direction.

PMID- 12228989
TI  - [Treatment of hypertension].

PMID- 12228990
TI  - [Science, art or culture?].

PMID- 12228991
TI  - [Matti Ayrapaa Award to Matti Haltia].

PMID- 12228992
TI  - [Antidepressant agents and discontinuation syndrome].

PMID- 12228994
TI  - [Survival skills in the flood of pharmaceutical information].

PMID- 12228993
TI  - [Hypertension in postmenopausal women].

PMID- 12228995
TI  - [Pain and cramps in upper abdomen].

PMID- 12228996
TI  - [Atopy is a disease caused by life style].

PMID- 12228997
TI  - [Evaluation and renewal of vaccination program].

PMID- 12228998
TI  - [Can the effects of immunization program decisions on the population be
      predicted?].

PMID- 12228999
TI  - [Vaccinations have their benefits--but what are their adverse effects?].

PMID- 12229000
TI  - [Hepatitis B and vaccination program policy in Finland].

PMID- 12229001
TI  - [Targets groups for influenza vaccinations will be revised].

PMID- 12229002
TI  - [Acellular pertussis vaccine--effective but expensive].

PMID- 12229003
TI  - [Is pneumococcal conjugate vaccine needed?].

PMID- 12229004
TI  - [Varicella vaccinations for everybody or for selected groups?].

PMID- 12229005
TI  - [Is the BCG--Bacillus Calmette-Guerin transferred to history?].

PMID- 12229006
TI  - [Problems in cooperation form a risk for the health of physicians].

PMID- 12229007
TI  - [Economic evaluation of an immunization program].

PMID- 12229008
TI  - [Vaccines of the future].

PMID- 12229009
TI  - ["If we don't have a family, we don't have a life!" Conceptions of popular class
      families caregivers of frail elderly people].
AB  - This research has a quality input that aims to reveal the concepts of popular
      class families caregivers of frail elderly people at their home, concerning the
      aspects that involve the meaning of care taking to the frail elderly in the
      family context. The methodology used is a case study of the ethnological kind.
      The data were collected by means of participant observation and interview with
      four families. Through the data analysis four themes related to the families
      conceptions were identified: the meaning of health-sicken, the meaning of family,
      the meaning of old age, the meaning of taking care of a frail elderly family
      member.

PMID- 12229010
TI  - [Sensitize: a way of education for care].
AB  - This article proposes to reflect about human care and ways of teaching it to
      future caregivers. The author describes a teaching experience in which she tried
      to sensitise the students--future nurse aides--for care, through "Meditation for
      the cure", proposed by Weiss (1998). Since it is a belief that there is a need to
      sensitise the caregivers to human care, the author stimulates the search for
      creative solutions to reach it.

PMID- 12229011
TI  - [Human care: purification action].
AB  - This article was originated by a request of some professors of the Masters Course
      in Nursing. The theme "bath", as an act of care, was developed, initially, on the
      meaning of moves. The esthetic of body movement, to the sound of music, was
      represented graphically, allowing to reach constructs as: relationship, physical
      contact, sharing, pleasure, satisfaction, cleanliness, reaproximation. The
      concept of "bath", understood through research in different bibliography and
      idioms, was translated as "purification". The meaning of "purification" was
      studied with an anthropological view. Many practices and rituals were perceived
      through history and human experience and bring with them tools that may help
      Nursing to create and recreate the experience and concept of human care. These
      elements and some contributions to comprehend care are shown in this study.

PMID- 12229012
TI  - [The nursing space in public health at the municipal health network of Porto
      Alegre].
AB  - Based on the author's experience at the municipal basic health network of Porto
      Alegre, this article presents a small historical retrospective of nursing work
      evolution on public health field, at Municipal Health Office of Porto Alegre
      (R.S., Brazil), characterizing the nurse's practice.

PMID- 12229013
TI  - [Social representation and its contributions to the health area].
AB  - This article approaches, in theory, a notion of Social Representations,
      describing its origin, concepts, fields of study and manners of approach, which
      are: dimensional, structural and dynamic. Some comments about the use of this
      framework in the health area are made, as well as how can it be used in Nursing.

PMID- 12229014
TI  - [Hospitalized newborn infants: the parents' experience].
AB  - This paper investigates parents' experiences during their newborns'
      hospitalization. It is a qualitative study. It takes place at Neonatal Care Unit
      of a School Hospital in Porto Alegre. The research subjects are parents of
      newborns placed in this Unit. The analysis process generates three topics:
      "Perceiving the baby's hospitalization as something difficult to experience",
      "Living the necessity of getting support", and "Living disease in a hospital".
      The importance of this work consists of articulating the elements which are
      present in parents' experiences, making possible a continuous nursing care with
      family valorization, specially through listening and supporting.

PMID- 12229015
TI  - [Rediscovering life despite cancer].
AB  - In a qualitative approach, using Case Study with two subjects, the authors took a
      look at the meaning attributed by them to the fact that they had had cancer,
      seeking to understand the repercussions resulting from this experience in their
      lives. The information obtained through semi-structured interviews was analyzed
      and four emerging themes were found: the perception of cancer, the experience of
      the disease as a learning process, our lives before, during and after cancer, and
      the significance of cancer in our lives.

PMID- 12229016
TI  - [Nurse activities in a Surgery Unit of a University Hospital].
AB  - The present study analyzes the process of the nurse work, classifying and
      quantifying the types of activities accomplished by this professional in a Inward
      Surgical Unit of the Hospital de Clinicas de Porto Alegre (HCPA). From this study
      on we point out alternatives to improve life quality in work and the quality of
      the patient care.

PMID- 12229017
TI  - [Characteristics of pregnant adolescents attended to by nursing appointments].
AB  - This article describes the social, obstetric and behavioral characteristics of
      the pregnant adolescents attended by nursing appointments. It is a quantitative
      and descriptive research. The data refers to the period between 1989 and 1999.
      The researcher reviewed 931 files of pregnant adolescents. Results show that the
      incidence of pregnancy is higher on the period between the ages of 15 and 19
      years old; the majority of the adolescents can count on an partner; they begin
      prenatal nursing appointments from the twentieth week of pregnancy on; and they
      have three or more appointments.

PMID- 12229018
TI  - [Scientific production about death and dying themes in a periodical].
AB  - The analysis of the production of scientific knowledge has been drawing the
      attention of many authors in several fields of study. The observation of this
      tendency consolidated my interest in embarking upon scientific knowledge by
      analyzing the material published by "OMEGA--Journal of Death and Dying", an
      American periodical journal that specifically refers to published matter
      connected with the themes of death and dying. With this objective, I analysed the
      production that this journal provided from 1980 to 1994, totalizing 526 articles.
      To the analysis characteristics of the authors and co-authors were considered,
      themes discussed, and the methods used, including the main methodological tools.
      Results enable us to discern the tendencies of thematic approach as well as how
      they are combined and the possibilities of a methodological approach.

PMID- 12229019
TI  - [Nursing knowledge production in Argentina, Chile, Paraguay and Uruguay].
AB  - Research is being pointed out as a path to nursing recognition. The knowledge
      production concerning the tendencies of research lines in nursing during the
      90's, in Argentina, Chile, Paraguay and Uruguay, took part of a study that had
      the purpose to know the impact of the nursing profession practice on health in
      Latin America and in the Caribbean Islands. The methodology used was the
      exploratory quantitative research, and the database used were Lilacs and Medline.
      The most frequent investigation themes refer to nursing profession (up to 13.2%).
      Regarding the lines of investigation in nursing, we found out that the nursing
      professional stood out with 41%, being technique and methodology the main
      approaches. Chile was the country that produced the largest amount of research,
      86.8% of the summaries. Referring to the financing source, no reference is made
      in 86.8% of the summaries. With reference to the number of authors involved with
      the published literature, 50.7% of the literature have only one author. The
      nurses should be aware to invest in the enlargement of this production.

PMID- 12229020
TI  - [Care and difference: from integration to fragmentation of being].
AB  - With this paper I intend to join to theorists who have discussed issues of
      difference and identity, with the aim of problematising some of the knowing/doing
      dimensions of nursing in contemporaneity. I am using as an analytical-theoretical
      background the Cultural Studies and Gender theories that develop a critical
      approach to post-structuralism. In the light of such a background I analyse some
      elements or constitutive aspects of the current theories on Care. I argue that to
      think care from the perspective of difference is to accept the challenge of not
      thinking about it as an action underpinned by scientific, philosophical and
      universal humanitarian assumptions, and start its theorisation and exercise as an
      action that is fundamentally political.

PMID- 12229022
TI  - [Literature review in a scientific work].
AB  - This article gathers some indispensable informations to ease the structure of
      literature review in a scentific work. The author has developed its content in
      phases aiming to show a logical sequency of how we do a scientic work. In this
      text is discussed the importance of the literature review, the strategies to do
      it, the search and organization of the bibliography and at last, how to write it.

PMID- 12229021
TI  - [Strategic thinking: a possibility of systematization of nursing supervision].
AB  - This is a study of strategic thinking as a possibility for systematization of
      nursing supervision. It is a perspective of collective reflection, aiming an
      effective intervention of nursing, without losing sight of the characteristics
      inherent to structures and dynamics of social relationships. It shows the need of
      a technical-political action of nursing staff, associating actions with ideas and
      acts of the wish to know, looking for construct/reconstruct practices and
      alternatives of change. A space of democracy that searches the change of social
      relationships seeking for mutual understanding, although only to verify
      disagreement in the end.

PMID- 12229023
TI  - [Occupational accidents among nursing personnel caused by perforating
      instruments].
AB  - The purpose was to conduct a survey on work accidents which occur due to sharp
      cutting instruments. The population studied consisted of nursing personnel who
      had suffered work accidents. A sample of 22 female workers was selected and the
      individuals were interviewed. The average age of this sample was 38 years old and
      there were 59.1% nursing assistants, 22.7% nurses, 9.1% nursing technicians and
      9.1% nursing attendants. The highest number of accidents occurred during the
      month of June and most of them around 3 PM. Most of the accidents reported were
      from the neonatal unit. The hands were the most affected parts of the body and
      the majority of the accidents were due to perforating instruments. When the
      accidents occurred, 50% were wearing gloves and 86.4% were vaccinated.

PMID- 12229024
TI  - [King's theory reach to families of persons with systemic arterial hypertension].
AB  - The aim was to verify the reach of the King's theory (1981) to families of
      persons with systemic arterial hypertension. The study was developed analyzing
      the reach of this theory; verification of its applicability in the family context
      as related by Moreira (1999); and construction of a concept of family with
      chronic sick persons which is compatible with the theory. The data showed that
      the theory is interaccionist, with vulnerable borders, and with content elements
      and context not well defined. In the focalized situation, a family definition
      with chronic sick persons was built, showing that is possible to use it as part
      of part of the subject of King's theory.

PMID- 12229025
TI  - [Perception of psychiatric patients' relatives concerning the available health
      care service].
AB  - This study focuses on the families of people suffering from mental disorders. It
      aims to identify how family members perceive current treatment site (Psychosocial
      Care Center). Using a qualitative approach, we interviewed relatives and
      constructed the methodological procedures through semistructured interviews. The
      discourses collected made possible for us to find out categories that portray the
      predicament of families trying to cope with mental disorders as they show the
      expectations and drawbacks by the treatment site.

PMID- 12229026
TI  - AHERF and Enron: increased scrutiny and change for healthcare CEOs and board
      members.

PMID- 12229027
TI  - [Information for the patient and the family].

PMID- 12229028
TI  - [St. John of God--A model of caring].

PMID- 12229029
TI  - [The connection between abortion and cancer of the breast: what all women in the
      world have a right to know].

PMID- 12229030
TI  - [The impact of varicocele--a nursing perspective].

PMID- 12229031
TI  - [Ebola fever, an out of control epidemic?].

PMID- 12229033
TI  - [The elderly and society, what reality. Nursing contributions].

PMID- 12229032
TI  - [Orientation: from concept to practice].

PMID- 12229035
TI  - [Remedy for many evils].

PMID- 12229034
TI  - [Treatment of arthritis of the knee].

PMID- 12229036
TI  - [Homage to Fernanda Alves Diniz].

PMID- 12229039
TI  - How much alcohol is safe to drink?

PMID- 12229040
TI  - Keep it local and stay healthy.

PMID- 12229041
TI  - Advancing practice in endoscopy.

PMID- 12229042
TI  - Basic life support and AED.
AB  - Cardiopulmonary arrest is a common and treatable cause of premature death. This
      Factfile discusses basic life support and automated external defibrillation.

PMID- 12229043
TI  - Examining the impact of spirituality on nurses and health-care provision.
AB  - The spiritual needs of patients are often neglected by health-care professionals
      who are already over-stretched by the 'physical' demands of their role. However,
      there is also ignorance of the spiritual needs of health-care professionals,
      especially nurses, who may have personal uncertainties about their own
      spirituality. This lack of understanding can lead to burnout.

PMID- 12229044
TI  - Procedural restraint in children's nursing: using clinical benchmarks.
AB  - This paper will explore the use of child restraint during common clinical
      procedures such as venepuncture, cannulation and lumbar puncture. A lack of
      research, guidelines and protocols on restraining children led a group of student
      nurses to develop a clinical practice benchmark on procedural restraint for the
      North West Clinical Practice Benchmarking Group.

PMID- 12229046
TI  - Time-limited psychotherapy in the community mental health team.
AB  - A community mental health team is offering clients short-term focal psychotherapy
      in the local area. Many clients find the team's base easier to attend than a
      central unit, and, with good communication and co-operation from other health
      care professionals, the relevant clinical nurse specialist is able to make good
      progress, as indicated by the case study described here.

PMID- 12229045
TI  - Targeted therapies for patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis is characterised by an auto-immune response that eventually
      leads to the destruction of affected joints. This has major implications for
      patients' lives, with many becoming debilitated within three years of diagnosis.
      This paper describes the body's auto-immune mechanism and outlines new therapies
      that seek to block the body's destructive response to itself.

PMID- 12229047
TI  - Nursing management of patients for greater renal transplant success.
AB  - There is now a greater choice of immunosuppressive agents that can be used in the
      care of kidney transplant patients. Concordance with treatment regimens is of
      prime importance and nurses working with this patient group have a key role in
      encouraging adherence to medication and helping patients to achieve a good
      quality of life.

PMID- 12229048
TI  - Evaluating a new technique for the treatment of chronic wounds.
AB  - This paper describes the techniques used to manage a complex foot wound in a
      patient with ankylosing spondylitis. Several methods were used initially to
      promote wound healing, but after some weeks progress ceased, requiring a review
      of the methods applied. Management was continued using a new approach to chronic
      wound care, resulting in complete healing.

PMID- 12229049
TI  - Clinical governance: implementing a change in workplace practice.
AB  - The development of a draft guideline on confirming placement of nasogastric tubes
      laid the basis for a senior nurse to use the principles of clinical governance to
      lead an improvement in practice. Key factors included risk management,
      dissemination of draft guidelines reflecting current evidence and changing
      practice. Good communication was vital to the project.

PMID- 12229050
TI  - Reducing hospital readmissions for people with heart failure.
AB  - With an ageing population and more people surviving heart attacks there are
      increasing numbers of people living with heart failure. Readmissions to hospital
      are often prolonged and costly. A number of nurse-led schemes have been
      successful in tackling the preventable causes of hospital readmissions and
      helping patients achieve a better quality of life in the community.

PMID- 12229051
TI  - Technology versus application--the view from the trade show floor.

PMID- 12229053
TI  - Computed tomographic and magnetic resonance coronary angiography: are you ready?
AB  - Within the next year or two, magnetic resonance angiography (MRA) and computed
      tomographic angiography (CTA) most likely will be used to deliver clinically
      useful images of the coronary arteries. The spatial resolution of CTA combined
      with new 16-detector scanners and cardiac imaging software will render views of
      the coronary arteries that will rival or surpass the spatial resolution and far
      surpass the contrast resolution of conventional coronary angiography (CA). MRA
      will potentially offer coronary artery imaging without the need for iodinated
      contrast injection. CTA and MRA of the coronary arteries offer distinct
      advantages over CA. Both CTA and MRA may be able to characterize plaques of the
      coronary arteries. Currently, CA can only detect degree of stenosis, collateral
      patterns and presence of dense calcification of the coronary arteries. CTA and
      MRA offer the promise of improved plaque characterization. CTA and MRA of the
      coronary arteries promise, at the least, to detect plaque not seen by CA and to
      offer some degree of characterization. According to some non-published data,
      advances in CT in the next five years may offer characterization of plaque equal
      to or superior to IVUS. To prepare for this "certainty," radiology departments
      must answer many questions. Each department will have it's own unique equipment
      requirements, though the size of the department and imaging volumes will
      determine what type of scanner will be purchased for CTA/MRA of the coronary
      arteries. Each department will require physicians and technologists trained in
      advanced CT and MRI imaging techniques including cardiac gating, 3D and 4D multi
      planar reconstructions, advanced coronary artery and cardiac anatomy, and
      personnel with advanced patient management skills to handle the unique needs of
      patients with coronary artery disease. To transition a department into full
      service cardiac CT or MRI, small steps can be taken over the next few years to
      allow referring physicians and department personnel to acquaint themselves to the
      needs of patients seeking coronary imaging. Current multi-detector CT scanners
      with two, four or eight detector rows perform prospectively gated coronary CT
      calcification scoring. While still controversial, coronary calcium scoring offers
      a reasonable non-invasive method for determining risk of significant coronary
      artery disease in asymptomatic patients. Once a department has experience with
      coronary calcium imaging of asymptomatic patients, the next step would be to
      consider coronary artery imaging. While four-detector or eight-detector CT
      scanners may be useful for this task, there is a growing consensus that 16 or
      more detector rows are required to perform consistent high quality CTA of the
      coronary arteries. The cost of these scanners is still undetermined. However, one
      can expect to pay at least double the cost of a conventional scanner for a 16
      detector unit at this time. With additional software for cardiac imaging, the
      costs can be well over a million dollars for a CT scanner. If the volume of
      additional patients from coronary CTA meets the promise of this new technology,
      the cost difference should be affordable even to smaller hospitals. As radiology
      professionals we possess equipment knowledge and have the imaging and technical
      skills to perform high quality cardiac imaging with CT and MRI. We need to add to
      and refine our knowledge of anatomy and become "team players" for management of
      patients with coronary and cardiac disease. If not us, then who? Are you ready?
      Are you willing to get ready?

PMID- 12229054
TI  - New tools for cost-effective delivery of breast imaging.
AB  - Breast imaging has a deserved reputation as a very difficult financial
      proposition for hospitals. Regulation, low reimbursement, costly new technologies
      and staff shortages all combine to create an operational environment that is
      difficult, at best. While it may not be possible for every hospital to make
      breast imaging profitable, it is the obligation of every hospital to make this
      and all service lines as cost-effective as possible. While the typical care
      episode in a hospital will include several different services or procedures, the
      breast-imaging patient is typically in the department or breast center for a
      single procedure. Consequently, all of the administrative and facility costs of
      the patient encounter must be borne by the reimbursement for the single
      procedure. Breast imaging involves relatively expensive technology and highly
      trained, and costly, technologists in its delivery. The costs of these inputs are
      relatively fixed; therefore material improvement can only be realized through the
      redesign of process. Analysis of the process of care delivery is critical to any
      discussion of the economics of breast imaging. Breast imaging can basically be
      divided into two categories: screening mammography and diagnostic procedures.
      This is a very important distinction, because screening mammography requires only
      general supervision, while the balance of breast imaging requires the direct
      supervision of the physician. Decoupling the physician from the examination
      allows the organization of screening delivery programs in highly efficient, high
      throughput systems. On the diagnostic side of breast imaging, the primary
      economic enhancement that can be realized is from the delivery of more than one
      procedure during the patient visit. Mammography has high fixed costs (technology
      and technologist) and, where high fixed costs are found, profitability is
      determined by process and volume. Where process can be optimized to a level that
      will allow a positive return for each mammogram, volume becomes a multiplier.
      Responding to congressional pressure exerted in 2001, CMS increased the 2002
      payment rate (global) for screening mammography from $69.23 (2001) to $81.81. The
      increase, however, was a mixed blessing, as it was all in the professional
      component ($22.18 to $35.48). In fact, the technical component was actually
      reduced by $0.74 from $47.07 to $46.33. While the reduction in payment for
      producing the screening mammogram is unjustified by the costs of producing that
      exam, the hardest blow was reserved for the payment rates for diagnostic
      mammography. As previously discussed, improving process and increasing volumes
      will improve the financial picture, but the problem of a single, low, procedure
      reimbursement remains. The implementation of CAD, however, has the ability to
      change that reality. CMS treats CAD as an add-on procedure. It cannot be billed
      as a stand-alone charge, but it is paid when billed in conjunction with a
      screening or diagnostic mammogram. The implications of the add-on character of
      CAD reimbursement are disproportionate to the amount of the payment, because it
      does not have to carry any costs other than those directly involved in its
      delivery. Breast imaging in general, and mammography specifically, will continue
      to present a challenge to the radiology administrator. With proper attention to
      process and volumes, and the very important contribution of CAD, however, breast
      imaging has the potential to not only pay its own way but to become profitable.

PMID- 12229055
TI  - Effective management starts with self management.
AB  - Each manager is his or her own best resource. As with any resource, managers
      should put effort into the development and improvement of that resource. A
      conscious effort to continuously improve personal resources will increase a
      manager's ability to effectively manage the efforts of others. These personal
      resources include initiative, integrity, organization of time and resources, and
      coping strategies. An individual's ability to practice initiative in their
      profession is only limited by their attitude. How do you answer the following
      questions: How much do I like my job? Do I have the desire to improve the skills
      and the abilities that will allow me to perform my duties more efficiently? How
      can I best achieve the goals expected of my department and me? In short, you will
      never improve your ability to manage unless you get moving! Don't wait for
      occasional pushes from above. Become an active and enthusiastic contributor to
      the development of plans and goals. Integrity is essential in establishing trust
      and loyalty between managers and their staff. Integrity is displayed to the
      department through honesty, consistency and fairness when dealing with
      operational problems. Most managers have an honest desire to learn how to manage
      their time, but don't have the time for it. In other words, we are so busy
      working inefficiently that we don't have time to become efficient. By organizing
      your space, you begin to organize the effective use of the time you spend in that
      space. Remember that your office is space, and space is a resource; demonstrate
      that you as a manager are concerned with the effective utilization of all
      organizational resources. Management is not for everybody. Some individuals may
      be better off realizing this early in the process. If an individual feels that
      management is their field, they should establish as much control over themselves
      and over the work place as they can if they hope to perform effectively for the
      long run. Some stress can be a positive motivator, but if the stress is
      unrelenting, if managers finds that they are chronically on the verge of anxiety,
      depression or panic, stress can also lead to personal ineffectiveness or
      eventually even physical or emotional illness.

PMID- 12229056
TI  - Middle management terminations: things HR probably won't tell you.
AB  - Being a manager or director, you may have received training for how to prepare
      your subordinates for layoffs or terminations. But, would you be prepared if the
      employee being terminated were you? Termination practice rules for a manager are
      very different from the rules required for a staff employee. There are many
      things you can do ahead of time to help you respond to being terminated: Keep
      copies of important information at home. If you are terminated, you may be asked
      to go home without going back to your office for an extended time. If you are
      given time to consider options, you will do that from your home. Keep a copy of
      an updated resume on file. If you do not have internet, email or fax capabilities
      at your home, get them. Many companies offer ongoing education as a benefit
      option. Take advantage of it. Ongoing education will keep as many doors open as
      possible as you look for another job. Keep copies of summary plan descriptions of
      your benefits, especially your retirement plan. To be prepared for change, you
      should know the "street value" of the benefits that you require. Make sure you
      have an attorney you can trust. Find out how many years of experience in
      employment law he or she has. Also, make sure your current attorney would not
      have a conflict of interest in handling your case against your company. There are
      no set laws for severance benefits, but your company may have a policy based on
      the years of service and the level of management. Upon receipt of a severance
      agreement, you should have it reviewed by your attorney. You will be given a time
      frame within which to sign or to respond to the proposal. The company will offer
      the least amount they feel you will accept, and it is appropriate to negotiate
      the severance agreement. Termination is not the time to make amends for hard
      feelings that may have been created in the workplace. The advice, "Always be a
      little nicer than you have to be," will bear fruit when you are looking for a new
      job. Your reputation will precede you. Remember that your job does not define who
      you are. You are defined by the endless decisions you have made, actions you have
      taken, the relationships you have built and the values you have portrayed. Your
      job description may change, but you will not. If you have done your job in a way
      that you can be proud of, then you have been successful. Change can be difficult,
      but change is always easier if you are prepared. Job changes are not always
      within your control, but preparing to accept the change is something that
      managers can control.

PMID- 12229057
TI  - Pet projects.

PMID- 12229058
TI  - Job burnout: symptoms, causes and solutions.

PMID- 12229059
TI  - When may a radiologist change or add an exam?

PMID- 12229060
TI  - Contemporary thoughts on the treatment of irritable bowel syndrome.

PMID- 12229061
TI  - Integrating "outcomes" into health systems.

PMID- 12229062
TI  - Integrating behavioral health and primary care through disease management.
AB  - Depression is often perceived as an isolated disease, and attempts to treat
      patients with depression from the managed care standpoint frequently reflect this
      silo mentality. Disease management programs for depression cannot succeed unless
      these initiatives are integrated through the primary care point-of-service and
      the PCPs treating the patient with depression understand this broader point of
      view.

PMID- 12229063
TI  - Eliminating fixed costs: Part I--Health system drivers.
AB  - Americans want less-bureaucratic, higher-quality, and above all, less-costly
      health care. Reducing the number of nurses, pharmacists, and others who care for
      patients is not a viable solution; fiscal constraints, which reduce fixed costs,
      are superior to other options in containing health costs. To this end, it is
      imperative that the U.S. reimbursement system be simplified. Posing as a major
      encumbrance are some deeply vested, highly placed self-interests that obstruct
      implementation of a partly private, partly public reimbursement system that would
      better serve patients, providers, and insurers. In part I of this two-part
      article, the author describes some of the drivers that are pushing health care
      costs to higher levels.

PMID- 12229065
TI  - Stats & facts. What makes an integrated system integrated?

PMID- 12229064
TI  - Cost effectiveness of kinetic therapy in preventing nosocomial lower respiratory
      tract infections in patients suffering from trauma.
AB  - Studies show that kinetic therapy (KT) reduces the incidence of early pneumonia
      and other complications, and shortens hospital length of stay. Using decision
      tree software in a retrospective analysis of one investigator's clinical data,
      the authors sought to determine if KT is cost effective for preventing nosocomial
      pneumonia and other complications in patients with critical illnesses. This
      analysis revealed that KT yielded 202 fewer infections per 1,000 patients
      suffering trauma--a cost savings of $6,695 per patient compared with standard
      care. On this basis, they conclude that prophylactic KT is cost effective and
      should be considered for at-risk patients in the critical care setting.

PMID- 12229066
TI  - Whole body scanning and the burden of proof: creating new costs.

PMID- 12229067
TI  - Five observations on electronic patient records.

PMID- 12229068
TI  - Shifting costs from high-cost to low-cost diagnosis-related groups?
AB  - Hospitals are commonly compared with each other within diagnosis-related group
      (DRG) categories. Administrators infer that hospitals with a higher cost per case
      within a DRG are less efficient than hospitals with a lower cost per case after
      case mix and severity adjustment. The authors assess whether hospitals that carry
      a heavy load of high-cost DRGs potentially distribute the added expenses of
      treating these patients onto their lower cost DRGs using data gathered from the
      47 hospitals in the University Hospital Consortium database between January 1994
      and December 1995. The results indicate that given standard hospital allocation
      practices, some of the costs associated with high-cost patients were likely
      shifted downward, thereby inflating the cost per case for less expensive
      patients. As researchers adopt more benchmarking methodologies, it is important
      to recognize that standard accounting practices in which cost shifting from one
      class of patient to another may impair the ability to understand the actual cost
      structure for classes of patients.

PMID- 12229069
TI  - Making it happen: approaches to involving consumers in Cochrane reviews.
AB  - The core work of the Cochrane Collaboration is the conduct of systematic reviews
      dealing with important health care questions. It is the policy of the
      Collaboration to involve consumers in all stages of the review process: from
      refining and prioritization of research questions through protocol design, to
      review conduct and ultimately dissemination of results. It has been difficult to
      achieve consumer involvement across all parts of the Cochrane Collaboration.
      Different approaches have been tried and different levels of success have been
      achieved. This article discusses consumer involvement in the Cochrane review
      process in relation to the 10 key principles that guide the work of the Cochrane
      Collaboration: collaboration, building on the enthusiasm of individuals, avoiding
      duplication, minimizing bias, keeping up to date, striving for relevance,
      promoting access, ensuring quality, continuity, and enabling wide participation.

PMID- 12229070
TI  - Involving people with severe mental illness in evaluation and performance
      improvement.
AB  - This article argues for the increased involvement of people with severe mental
      illness and consumers of other health and mental health services in evaluation
      and performance improvement in the organizations from which they receive
      services. Among other reasons, consumers can bring a different perspective to the
      selection of areas to evaluate, such involvement is consistent with some models
      of program evaluation, and the process of participation itself can be empowering
      to consumers. Based on a review of the literature and the experiences of a public
      psychiatric hospital in involving consumers in evaluation and performance
      improvement, the authors exemplify how mental health consumers can participate in
      each stage of the evaluation process, ranging from the initial stage of posing
      evaluation questions to the final stage of acting on evaluation findings. Next,
      challenges to consumer involvement are described. Guidelines are then offered for
      involving consumers of health and mental health services in evaluation and
      performance improvement.

PMID- 12229071
TI  - Impact of HIV/AIDS education on health care provider practice: results from nine
      grantees of the Special Projects of National Significance Program.
AB  - The study assessed the impact of health care provider HIV/AIDS education and
      training on patient care from nine Special Projects of National Significance.
      Telephone interviews were conducted with 218 health care providers within 8
      months, on average, following completion of training. Respondents provided
      examples of how the SPNS trainings affected their provision of patient/client
      care. Transcribed comments reflecting change in patient/client care were
      classified by independent coders under 1 of 10 broad practice change categories.
      Eighty-two percent of the trainees identified at least one instance of change in
      patient/client care as a function of their training experience. Self-reported
      findings included changes in the number/types of patients seen, interpersonal
      interactions with patients/clients, HIV testing and counseling practices,
      patient/family education, infection control, advocacy, referrals and
      collaboration, documentation, and other service changes.

PMID- 12229072
TI  - A qualitative evaluation of an HIV/AIDS respite care service in Victoria, Canada.
AB  - The Victoria AIDS Respite Care Society (VARCS) has provided respite care to
      people living with HIV/AIDS (PLWAs) since 1991. In 1998, an evaluation of VARCS
      services was undertaken to gain a better understanding of the VARCS model of
      community-based care. The evaluation was comprised of four components including
      an examination of the historical evolution of VARCS, an account of the community
      development processes used, a description of VARCS services, and an analysis of
      the impact and outcomes of VARCS services. This article highlights qualitative
      findings from the impact and outcomes component of this study. Guided by
      principles of participatory action research, this project included interviews
      with 85 participants. Eight themes emerged from the analysis that appeared to
      speak to the qualitative impact and outcomes of VARCS service. Actions taken by
      VARCS as a result of the evaluation findings are discussed as are the study
      limitations.

PMID- 12229074
TI  - Statutory CPD introduced in the UK.

PMID- 12229073
TI  - Tracking procedures for locating high-risk youth.
AB  - Few published works are available that provide a comprehensive description of
      tracking procedures. This article describes the data collection tracking protocol
      that was used in Project Towards No Drug Abuse (Project TND), to follow high-risk
      youth over a 5 1/2 year period. Youth were followed from 1994 through 2000. A
      total of 35% of these youth were assessed 5 1/2 years later. Collapsing across
      the last two waves, 46% of these youth were followed an average of 5 years later.
      These procedures may be helpful in tracking highly mobile youth.

PMID- 12229075
TI  - The mercury burden in waste water released from dental clinics.
AB  - The aim of this study was to estimate mercury burden in waste water samples
      collected during one working day in 27 dental clinics. The samples were subjected
      to authorized analysis using the technique of QS-IE Enhanced Cold Vapour Mercury
      Analyzer to estimate the amount of mercury discharged. The mean value of mercury
      discharged was 2.49 parts per billion (ppb) for the clinics equipped with amalgam
      separators and 94.75 ppb for the clinics without amalgam separators. Some of the
      small amalgam particles released when new fillings are placed or during removal
      of old restorations form a sediment in tubes and drains. The remaining particles
      are carried with the waste water stream to the local purifying plant. If
      threshold values for heavy metal content including mercury are exceeded, the
      sludge is not allowed to be recycled as fertiliser. Installation of an approved
      amalgam-separating apparatus in dental clinics is recommended so as to reduce
      considerably the discharge of mercury into waste water.

PMID- 12229076
TI  - Accurate diagnosis of occlusal carious lesions--a stereo microscope evaluation of
      clinical diagnosis.
AB  - This study was undertaken to validate the caries status of 214 teeth by serial
      sectioning and microscopy after caries diagnosis using four methods. Two hundred
      and fourteen extracted human teeth with varying degrees of caries were mounted in
      the jaws of nine training manikins. All tooth surfaces were examined and recorded
      for caries by four dentists using bitewing radiographs, fibre-optic
      transillumination (FOTI), mirror alone and a mirror and sharp probe on two
      separate occasions. Thereafter the teeth were serially sectioned and assessed
      microscopically for depth of caries lesion on a graded score of 0-7. This report
      assessed the diagnostic outcome of 2,183 observations for occlusal surfaces.
      Sound diagnoses predominated over unsound until caries was present in the inner
      half of dentine. Specificity was between 90% and 95% and sensitivity 26% and 50%
      depending on which diagnostic method was used and where the sound/unsound
      threshold was set. Negative and positive predictive values were similarly
      influenced and varied between 53% and 80% and 73% and 90%, respectively. Probit
      analysis showed no significant differences (P < 0.05) between examiners and
      diagnostic methods. Diagnosis of occlusal caries undertaken in an in vitro
      simulated clinical situation is inaccurate until the caries lesion extends deep
      into the dentine no matter which of the four methods was used.

PMID- 12229077
TI  - Posterior composite resin restorations. Part 3. Matrix systems.

PMID- 12229078
TI  - Dental curing lights--maintenance of visible light curing units.
AB  - Successful curing depends directly on many factors of which the most important is
      the correct functioning of the curing unit to emit light of sufficient intensity
      and quality. If the contribution of any of these factors is at a less than
      adequate level, the light-sensitive materials will not polymerise completely,
      which in the long term may be responsible for secondary caries and decreased
      longevity of the restoration. Factors which may reduce the light output include
      ageing of the bulb and filter, damage of the light guide or fibre optics,
      deposits on the light tip due to composite build-up or autoclave scale, erosion
      of light tip surface due to immersion sterilisation, and line voltage
      fluctuations. Recent studies carried out to investigate the effectiveness of
      curing lights in clinical use show that most practitioners are unaware of the
      importance of routine monitoring, care and maintenance of curing lights. This
      paper reviews some of the available literature on the monitoring, care and
      maintenance of curing lights, including information on the influence that some of
      these may have on the intensity emitted by the curing light.

PMID- 12229079
TI  - Dentine bonding agents--a review of adhesion to dentine.
AB  - Although constant innovation has improved the performance of dentine adhesives,
      the true mechanism of resin adhesion to dentine is still not clear and the
      optimal dentinal surface pretreatment has yet to be determined for adhesive
      integrity of resin to dentine. The integrity of the collagen fibrils left exposed
      upon acid etching seem to play a major role in the mechanism of adhesion and
      intermingling of the adhesive monomers with the filigree of collagen fibers or
      hybrid layer should be considered the paramount dentine bonding mechanism.
      Definite trends are emerging but more research is necessary before general
      conclusions can be made about the functions of different bonding agents. The all
      in-one self-etching/self-primer bottle systems are relatively new to the market
      and need more research before they can be advocated as the agent of choice.

PMID- 12229080
TI  - Mass disasters. Part 1. Role of the general dentist.
AB  - In this article, the first of two on the involvement of dentists in a mass
      disaster, the focus is primarily on mass disasters in general, some common
      characteristics and types of disasters, those agencies or individuals involved in
      the management of a disaster, the different phases of a disaster and the position
      of the forensic dental identification team (FDIT). Part 2 will deal with the
      functions, responsibilities and jurisdiction of the FDIT during the various
      phases of a disaster and more specifically immediately after the disaster.

PMID- 12229081
TI  - Assistance for the underprivileged.

PMID- 12229082
TI  - [Consultation: R77.00 versus R54.88--Code 8101].

PMID- 12229083
TI  - Lessons for our future. What tomorrow's managers need to know.

PMID- 12229084
TI  - CCRC 'phantom income'. Short-run financial squeeze or bursting bubble?

PMID- 12229085
TI  - Urinary incontinence in elderly women.

PMID- 12229086
TI  - Between a rock and a hard place. Navigate the legal constraints of involuntary
      discharge.

PMID- 12229087
TI  - Racing toward the deadline.

PMID- 12229088
TI  - What's good caregiving worth? There are myriad ways to show how much you value
      your frontline caregiver. Ready to walk the walk?

PMID- 12229089
TI  - Trolling the online database. Wakeup call: what looks like fact may be a fish
      story.

PMID- 12229090
TI  - Blueprints for reform. Interview by Suzanne Bilyeu.

PMID- 12229092
TI  - Has consolidation hurt the growth of PD?

PMID- 12229093
TI  - AAKP Patient Plan provides knowledge to kidney patients.

PMID- 12229094
TI  - AAKP reaches out to CKD population.

PMID- 12229095
TI  - Care and maintenance of hemodialysis catheters and subcutaneous vascular access
      devices--a nurse's perspective.

PMID- 12229096
TI  - A network QI project/Part II. Decreasing the utilization of catheters for
      permanent vascular access.

PMID- 12229097
TI  - Evaluating the impact of a physical rehabilitation program for dialysis patients.

PMID- 12229098
TI  - Delivery of care.

PMID- 12229099
TI  - ED nurses are the front line for assessing smallpox exposure.

PMID- 12229100
TI  - Using the umbilicus for catheterization.

PMID- 12229101
TI  - Holistic nursing: is it right for you?

PMID- 12229102
TI  - Code Blue. A closer look.

PMID- 12229103
TI  - What's causing that itch?

PMID- 12229104
TI  - Help for ARDS patients.

PMID- 12229105
TI  - Blood pressure cuffs.

PMID- 12229106
TI  - Is it patient abandonment--or not?

PMID- 12229107
TI  - [Ghrelin, growth and obesity].

PMID- 12229108
TI  - [Adversive environmental hormones and reproductive health].

PMID- 12229109
TI  - [How do I diagnose and treat ventricular extrasystoles?].

PMID- 12229110
TI  - [Antipsychotic agents and weight gain].

PMID- 12229112
TI  - [Finglish].

PMID- 12229111
TI  - [Recurrent miscarriage].

PMID- 12229113
TI  - [Large granular lymphocytic leukemia].

PMID- 12229114
TI  - [Unilateral, rapidly progressing claudication].

PMID- 12229115
TI  - [Treatment of paracetamol intoxication. Correctly given antidote treatment will
      prevent liver damage].

PMID- 12229116
TI  - [Three weeks lasting fever in a healthy school boy].

PMID- 12229117
TI  - [Breast self-examination--a comparison of routine teaching and a more
      comprehensive patient education program].

PMID- 12229118
TI  - [Cellular and humoral immune responses against WT1 products overexpressed in
      hematopoietic malignancies].

PMID- 12229119
TI  - [Monoclonal gammopathy of undetermined significance (MGUS): establishment of
      premyeloma concept].

PMID- 12229120
TI  - [Efficiency of protective isolation in allogeneic stem cell transplantation in
      children].
AB  - Forty children with hematological malignancies, who underwent allogeneic
      hematopoietic stem cell transplants between September 1994 and May 2001, were
      divided into 2 groups according to their infection control procedure; the
      standard protective isolation and the efficient protective isolation groups.
      Efficient protective isolation procedures included well-cooked foods and oral
      prophylaxis with new quinolones and antifungal drugs, while inhalation of
      antibiotics and antifungal drugs was suspended. We then compared the febrile
      index (= X/Y) [febrile period (X) of > 38.5 degrees C and the days (Y) with a
      post-transplant neutrophil count < 500/microliter] between the two groups. We
      discovered no significant difference between the febrile index of the two groups
      (0.25 vs. 0.38, p = 0.08), regardless of the type of transplantation (0.36 vs.
      0.38, p = 0.14). The efficient protective isolation procedure was therefore
      feasible in this clinical setting.

PMID- 12229122
TI  - [An elderly non-Hodgkin lymphoma patient with a massive tumor of the heart].
AB  - We report on an elderly patient with a malignant lymphoma forming a huge mass in
      the heart. An 82-year-old woman became aware of general fatigue and a cough in
      August 1999. Her right supraclavicular, bilateral axillary, and right inguinal
      lymph nodes were swollen. A hypodermical mass in the right frontal chest was
      detected. Her left axillary lymph node was biopsied. She was diagnosed as having
      non-Hodgkin lymphoma, diffuse large cell type, B-cell type. Computed tomography
      scans showed a markedly thickened right ventricular wall of the heart, swollen
      lymph nodes of the mediastinum, bilateral pleural effusions, and a tumor in the
      spleen. Lymphoma cells were found in the pleural effusion, and the lymphoma was
      diagnosed as clinical stage IV. Hypofunction of the heart, ejection fraction (EF)
      49%, was demonstrated with transthoracic echocardiography. EF increased to 70%
      after 3 courses of chemotherapy with CHOP regimen. All lesions disappeared after
      6 courses of chemotherapy were completed. After consolidative radiotherapy with a
      total dose of 37 Gy to the mediastinum and heart, bilateral pleural effusions,
      elevation of the patient's lactate dehydrogenase level and soluble IL-2 receptor
      value were recognized, which suggested relapse of the lymphoma, although
      histopathological confirmation could not be realized.

PMID- 12229121
TI  - [Hematopoietic stem cell transplantation with conditioning regimens containing
      melphalan in pediatric patients with acute lymphoblastic leukemia].
AB  - A multicenter comparative study was carried out to investigate the efficacy and
      safety of hematopoietic stem cell transplantation with conditioning regimens
      containing melphalan in pediatric patients with acute lymphoblastic leukemia. One
      hundred twenty three patients at a variety of remission stages were eligible for
      study participation. Eighty-nine were transplanted with allogeneic grafts and 34
      patients with autologous grafts (23 cases with bone marrow and 11 cases with
      peripheral blood stem cells). Conditioning regimens used were as follows: (A)
      melphalan and busulfan for 40 patients, (B) melphalan, busulfan and TBI for 44
      patients, (C) other regimens for 39 patients. To accelerate engraftment G-CSF
      (lenograstim) was administered as a 1-hour or 24-hour drip infusion daily at 5
      micrograms/kg from day 5 until hematological recovery. The five year disease free
      survival (DFS) was 63% for 42 patients at CR 1, 41% for 41 patients at CR 2 and
      33% for 40 patients at other stages. There was no significant difference in the
      DFS between allogeneic-transplantation and autologous-transplantation in all
      disease stages. In patients at remission stage for CR 1 and CR 2, the 5-year DFS
      by conditioning regimen was 63% for regimen (A), 54% for regimen (B) and 54% for
      regimens with melphalan and TBI. There was no significant difference in the DFS
      between the groups. Serious complications such as renal failure were observed in
      11%, veno-occlusive disease in 9%, and interstitial pneumonia in 9%. The most
      dominating cause of death was relapse in the disease (48% of deaths) which was
      most commonly observed in autologous transplantation. Contrary to that, treatment
      related toxic death was the most frequent cause of deaths in allogeneic
      transplantation.

PMID- 12229123
TI  - [Lineage switch on recurrence from minimally differentiated acute leukemia (M0)
      to acute megakaryocytic leukemia (M7)].
AB  - Phenotypic switch in acute leukemia is a rare phenomenon. We report on a female
      infant with minimally differentiated acute leukemia (M 0) which underwent a
      lineage switch on relapse. In March 1997, a 1-year-8-month old girl was admitted
      to our hospital with a high-grade fever and generalized purpura. Bone marrow
      showed 84% blasts. The blasts were negative for peroxidase, periodic acid-Schiff
      and alpha-naphthyl butyrate esterase. Immunophenotypic analyses of the blast
      cells were positive for CD 13, CD 33 antigens, as well as CD 34. Lymphoid markers
      all were negative. Though some blasts morphologically demonstrated cytoplasmic
      blebs, CD 41 was negative and ultrastructural platelet peroxidase was absent.
      Based on these hematological features, the patient was diagnosed as having AML-M
      0. She was treated according to the Children's Cancer and Leukemia Study Group
      schedule and a complete remission was achieved 1.5 months after starting
      induction therapy. However, she relapsed in spite of continued chemotherapy in
      July 1997, when the cytomorphological pattern changed and the patient was
      diagnosed both morphologically and immunologically as having M 7. Electron
      microscopy revealed platelet peroxidase (+) and CD 41 (+). Cytogenetic studies on
      relapse demonstrated inv(3) (q 21 p 25). We attempted aggressive reinduction
      therapy, but without effect. The patient simultaneously developed severe
      pneumonia and died in February, 1998. A lineage switch on relapse and resistance
      to chemotherapy may be associated with the occurrence of genetic aberration.

PMID- 12229124
TI  - [Human herpesvirus-8 negative primary effusion lymphoma with complete clinical
      remission after removal of ascites].
AB  - A 58-year-old HIV-negative woman was admitted to our hospital with abdominal
      distension. She had a 5-year history of hypothyroidism and a 4-year history of
      diabetes mellitus. Physical examination revealed ascites. There was no
      lymphadenopathy or splenomegaly. Laboratory examination showed elevated levels of
      serum LDH and Al-p, polyclonal hypergammaglobulinemia, and was positive for anti
      nuclear antibody, several autoantibodies and HCV-RNA. A computed tomographic scan
      of the abdomen and chest showed massive ascites, but there was no evidence of
      tumor masses or lymph node enlargement. Cytologic examination of the ascitic
      fluid revealed numerous abnormal lymphocytes which by flow cytometry demonstrated
      expression of CD5, CD19, CD20, and CD4. Cytogenetical analysis demonstrated a
      hyperdiploid karyotype, with numerical abnormalities. Southern blot analysis
      demonstrated rearranged monoclonal bands in JH and c-mycgenes. Polymerase chain
      reaction (PCR) analysis failed to detect the genomes of EBV and HHV-8 in the
      abnormal lymphocytes. A diagnosis of primary effusion lymphoma of B cell lineage
      was made. Following abdominal paracentesis, the patient remained in complete
      clinical remission for 7 months and died of an unrelated cause (cerebral
      bleeding). The present case demonstrated an HIV-, HHV-8-, and EBV-negative, and
      HCV-positive primary effusion lymphoma of B cell lineage, with a unique clinical
      course.

PMID- 12229125
TI  - [Indolent primary gastric adult T-cell leukemia/lymphoma with recurrent lesions
      limited to the stomach and duodenum].
AB  - A 75-year-old man visited our hospital complaining of heartburn in November 1997.
      Gastroscopical examination revealed ulcerous protruding extended from the gastric
      antrum to body and a flat, elevated lesion in the greater curvature of the
      stomach. Biopsy specimens revealed a CD4-positive malignant lymphoma. The serum
      anti-human T-lymphotrophic virus type I (HTLV-I) antibody test was positive. He
      was diagnosed as having primary gastric adult T-cell leukemia/lymphoma (ATLL;
      acute type). Complete remission was achieved with chemotherapy. In December 1998,
      the patient experienced a relapse. The lesions were limited to the region between
      the upper gastric body and the fornix and disappeared with radiation therapy. A
      second relapse was detected in the gastric greater curvature and descending
      portion of the duodenum in May 1999 but spontaneously disappeared in 5 months.
      The third relapse in May 2000 was systemic. Monoclonal integration of the HTLV-I
      provirus was observed in DNA extracted from ascitic lymphocytes. Chemotherapy was
      resumed, but the response was poor. The patient subsequently died of respiratory
      failure as a result of pneumonia. Although gastrointestinal involvement is
      frequent in ATLL, this appears to be a rare case of an idolent clinical course
      with lesions limited to the stomach and duodenum for 30 months.

PMID- 12229126
TI  - [CD 56-positive acute myeloid leukemia (AML-M 1) with t(16;21) (p11;q22)
      presenting an extramedullary tumor in the right breast at relapse].
AB  - A 46-year-old woman was diagnosed as having acute myeloid leukemia (M 1) with
      translocation t(16;21) (p11;q22). The leukemic cells were positive for CD 13, CD
      33, CD 34, CD 41, CD 56 and HLA-DR. After induction chemotherapy, the patient
      achieved complete remission (CR). However, 8 months later she relapsed with
      various additional chromosomal abnormalities. Although the patient achieved a 2nd
      CR after re-induction chemotherapy, the patient had extramedullary tumors in the
      right breast twice and relapse occurred frequently. The tumor cells were
      characterized by the same immunophenotypes and t(16;21) with additional 1 q
      trisomy. Although there was no evidence of hematological relapse, another type of
      1 q trisomy was observed. Furthermore, an increase of abnormalities with 1 q
      trisomy was noted concomitant with re-increase in the number of blasts. The
      patient underwent allogeneic bone marrow transplantation (BMT), but she died from
      BMT complications. The case could have been a karyotype of t(16;21) with
      additional chromosomal abnormalities through consecutive approaches. Because of
      the high occurrence rate of relapse, we consider various additional chromosomal
      abnormalities and the expression of CD 56 as prognostic factors of this
      condition.

PMID- 12229127
TI  - [Intravascular large B cell lymphoma with migratory local high density shadow by
      chest CT and diagnosed by transbronchial lung biopsy].
AB  - The intravascular large B cell lymphoma (IVL) is a rare subtype characterized by
      the presence of lymphoma cells in the lumina of small vessels. Reported here is
      the case of a 68-year-old woman with a high-grade fever uncontrolled by
      antibiotics or antipyretic drugs, and elevation of the serum LDH and sIL-2R
      levels. After she was admitted, dyspnea, hypoxia, and severe body weight gain
      with leg edema gradually developed. Chest computed tomography (CT) revealed a
      characteristic migratory local high density area typical of atelectasis. A
      diagnosis of IVL was made with a transbronchial lung biopsy (TBLB) and
      immunohistochemical analysis. The patient was treated with combination
      chemotherapy (modified CHOP), and her symptoms of dyspnea, hypoxia, pyrexia and
      leg edema were quickly resolved. The level of LDH and sIL-2R returned to normal,
      and a complete response was obtained. Although diagnosis of IVL is difficult, an
      early and appropriate diagnostic procedure (biopsy of tissue with vessels, such
      as lung and skin, is required) will improve the prognosis of IVL.

PMID- 12229128
TI  - [Chronic myelogenous leukemia treated with non-myeloablative stem cell
      transplantation after discontinuing myeloablative stem cell transplantation due
      to mental aberrations].
AB  - A 54-year-old woman with chronic myelogeneous leukemia was admitted to our
      hospital on February 15th, 2001 to undergo allogeneic bone marrow transplantation
      (BMT). We started the transplantation preconditioning with busulfan and high-dose
      cyclophosphamide on February 22nd, 2001. However, symptoms of a psychiatric
      nature, such as hallucination, persecution complex, auditory hallucination and
      sleeplessness, occurred by the third day of treatment with busulfan. Thus, we
      decided to discontinue conditioning and stopped the administration of BMT at that
      point. However, pancytopenia persisted for more than 20 days. She finally
      underwent BMT followed by reduced-intensity conditioning with fludarabine and ATG
      from a sex-mismatched, HLA-identical sibling donor on April 19th, 2001. To
      prevent any exacerbation of the psychotic symptoms, the patient was hospitalized
      in a laminar flow instead of a bio-free room. Graft-versus-host disease occurred
      on the 32nd hospital day, and was brought under control by steroid treatment.
      Achievement of complete chimeras was confirmed on the 54th hospital day. Her
      mental condition was kept stable with antidepressant drugs and tranquilizers,
      although minor changes in the combination of drugs were required to treat
      transient exacerbation of psychosis after a short period at home. She was
      discharged on September 1st, 2001. We think that non-myeloablative stem cell
      transplantation is a useful treatment for patients with hematological malignancy
      complicated with psychiatric disorders.

PMID- 12229129
TI  - [Leukemic meningitis in B-cell prolymphocytic leukemia].
AB  - An 84-year-old woman was admitted because of anemia and marked leukocytosis. The
      white cell count was 237,660/microliter, with 93% abnormal lymphoid cells. The
      cells had abundant cytoplasm and prominent nucleoli. They were positive for CD 5,
      19, 20, 22, 23, HLA-DR, IgM, IgD and kappa chain. Thus, a diagnosis of B-cell PLL
      was made. Chromosome analysis disclosed a complex karyotypic abnormality. Massive
      splenomegaly was detected by abdominal computed tomography. No external or
      internal lymphadenopathy was found. The patient was intermittently treated with
      etoposide. Although the white cell counts had been suppressed, she refused to
      take the drug because of side effects. When the white cell count exceeded more
      than 200,000/microliter again, she developed severe headache, diplopia, nausea,
      and vomiting. A lumber puncture disclosed infiltration of the prolymphocytes in
      the cerebrospinal fluid. Though intrathecal chemotherapy alleviated the symptoms
      and the leukemic cells disappeared, the effects were transient. When the therapy
      was withheld because of bone marrow suppression, the meningitis recurred and the
      symptoms progressed. The patient died six months after the initial presentation.

PMID- 12229130
TI  - [Successful treatment of hairy cell leukemia prolymphocytic variant with 2'
      deoxycoformycin].
AB  - The hairy cell leukemia prolymphocytic variant, a subtype of hairy cell leukemia,
      is an extremely rare disease, especially in Japan. We report a case in which
      treatment with 2'-deoxycoformycin (DCF) improved the clinical features of the
      disease. The patient, a 70-year-old female, was first treated with 2
      chlorodeoxyadenosine, but showed only transient improvement in the hematological
      findings. DCF was then administered every week. Following the start of this
      treatment, the leukemia cell count rapidly decreased and the platelet count
      simultaneously increased. This effect of DCF has so far been long term. More
      clinical studies are needed to confirm the therapeutic value of DCF.

PMID- 12229131
TI  - [Postoperative analgesia with morphine with or without diclofenac after shoulder
      surgery].
AB  - Balanced analgesia using a narcotic and a nonsteroidal anti-inflammatory drug has
      been successfully tested for postoperative analgesia. This study was designed to
      examine the efficacy of such combination therapy after shoulder surgeries. Twenty
      ASA physical status I or II patients, scheduled for shoulder surgeries under
      general anesthesia, were randomly assigned to either morphine (M) group (n = 10),
      who received IV morphine patient-controlled analgesia (PCA) alone (2 mg as a
      bolus, lock-out interval of 10-minutes, and 10 mg as 1-hour limit for 48 hours),
      or morphine + diclofenac (M + D) group (n = 10), who received, in addition to
      morphine PCA, diclofenac suppositories 50 mg.8 h-1 starting immediately before
      surgical incision for 48 hours. Postoperative analgesic profiles, such as visual
      analog scale (VAS) at rest and on movement, and cumulative morphine consumption,
      the incidence and extent of side effects (nausea, vomiting, and time till the
      first bowel movement), and other complications were recorded. The two groups were
      similar demographically. Patients in the M + D group required 15.1 +/- 9.0 mg of
      morphine within 48 hours after surgery, while those in the M group required 30.5
      +/- 21.0 mg of morphine (P < 0.05). No significant differences in VAS at rest and
      on movement were observed between the two groups. The time till the first bowel
      movement was significantly shorter in the M + D group. Our data suggest that
      diclofenac suppositories 50 mg.8 h-1 starting immediately before surgery for 48 h
      are effective adjuvant in reducing post-shoulder surgery morphine requirement and
      retardation of bowel movement.

PMID- 12229132
TI  - [A comparative study of membrane destructive action of dibucaine HCl and
      bupivacaine HCl].
AB  - Membrane destructive action of dibucaine HCl and bupivacaine HCl was examined in
      vitro using red blood cells. The EC50 value (local anesthetic concentration
      needed to destroy half of red blood cells in vitro) of each local anesthetic was
      determined at pH 5.0, 6.0 and 7.0 to obtain a pH-EC50 curve. The pH change of
      each commercially available local anesthetic solution (0.3% dibucaine HCl and
      0.5% bupivacaine HCl) was also determined with the dilution by cerebrospinal
      fluid to yield a pH-concentration curve. The EC50 values of dibucaine HCl were
      0.17%, 0.18% and 0.13% at pH 5.0, 6.0 and 7.0, respectively. The EC50 values of
      bupivacaine HCl were 1.36% and 1.36% at pH 5.0 and 6.0, respectively. The EC50
      value of bupivacaine HCl at pH 7.0 could not be measured for the low solubility
      in water at pH 7.0. The pH-EC50 curve of dibucaine HCl intersected the pH
      concentration curve, although the pH-EC50 curve of bupivacaine located in the
      right side (higher concentration) for the pH-concentration curve of bupivacaine
      HCl, which implies clinical level of dibucaine HCl may produce membrane
      destruction action and low possibility of membrane destruction with clinical
      level of bupivacaine HCl.

PMID- 12229133
TI  - [The effectiveness of perioperative intravenous flurbiprofen in minor ear, neck
      and nose surgery].
AB  - To evaluate the effect of perioperative intravenous administration of
      flurbiprofen, a nonsteroidal anti-inflammatory drug, on the postoperative pain
      after minor ear, neck and nose surgery, eighty patients were randomly allocated
      into three groups. Control group of 40 patients, received a placebo. The second
      group (n = 20) received 1 mg.kg-1 flurbiprofen i.v. at the end of surgery, and
      the third group (n = 20) received the same dose of flurbiprofen before the start
      of surgery. The ratio of the patients and the time for requirement of analgesics
      after the operation and the serum concentration of flurbiprofen were assessed.
      The ratio of the patients who required analgesics was higher in control group
      (0.45, 0.35 and 0.10 in each group). The time without analgesics was longer in
      pre-treatment group. The serum concentration of flurbiprofen decreased in pre
      treatment group at the end of surgery, but the effectiveness of flurbiprofen on
      postoperative pain might be more apparent in pre-treatment group. Administration
      of flurbiprofen before the start of surgery is more effective for peri-operative
      analgesia in minor ear, neck and nose surgery.

PMID- 12229134
TI  - [Efficacy of bispectral index monitoring in improving anesthetic management,
      economics, and use of the operating theater].
AB  - This study was designed to assess the efficacy of bispectral index (BIS)
      monitoring in reducing the amount of volatile anesthetics used and improving
      recovery profiles. Sixty patients (ASA physical status 1 or 2) undergoing various
      surgical procedures under sevoflurane/nitrous oxide anesthesia were studied. The
      patients were randomly assigned to two groups of which anesthesia was carried out
      with (BIS group) or without (control group) monitoring BIS, and in the latter,
      anesthesiologist was blinded to the BIS values. In the BIS group, sevoflurane
      concentration was adjusted to achieve target BIS values between 40-60 during
      surgery and 60-75 during the final 15 min of the surgery. Drug usage, incidence
      of intraoperative complications, and recovery parameters were recorded.
      Demographics were similar between the groups. The BIS values in the BIS group
      were significantly higher compared with those of control group in which BIS
      values were blinded during anesthesia. The sevoflurane consumption in the BIS
      group (17 +/- 3 ml.h-1) was lower than control group (22 +/- 3 ml.h-1). Compared
      with control group, the patients in BIS group were extubated earlier and became
      eligible for discharge earlier from recovery room than control group. There was
      no significant difference in the incidence of intraoperative complications
      between the groups. Titrating sevoflurane concentration with BIS monitoring
      during anesthesia decreased anesthetic consumption and improved recovery compared
      with standard clinical practice.

PMID- 12229135
TI  - [Epidural cooling for thoracoabdominal aortic surgery].
AB  - This report summarizes our experience with the use of epidural cooling for
      protecting spinal cord ischemic injury in patients receiving thoracoabdominal
      aortic surgery. Of 8 cases with thoracoabdominal aortic surgery, we used epidural
      cooling in 5 cases. Epidural cooling was performed through an epidural catheter
      placed at Th 11 x 12 using chilled saline. Spinal cord temperature was maintained
      at approximately 28 degrees C. None of the 5 cases had paraplegia or paraparesis
      whereas two of 3 cases without epidural cooling had permanent paraplegia. In one
      case with paraplegia, we could not detect any changes in spinal evoked potential
      until the end of graft anastomosis. We monitored motor evoked potential in the
      recent 2 cases. We believe that epidural cooling combined with motor evoked
      potential monitoring appears to be a satisfactory strategy for preventing
      ischemic spinal cord injury in thoracoabdominal aortic surgery.

PMID- 12229136
TI  - [One-lung anesthesia was successfully maintained by means of Fogarty Catheter in
      infants].
AB  - We experienced one-lung anesthesia using Fogarty catheter as a selective
      bronchial blocker in two infants. First case was a one-year and ten month-old
      female who underwent partial resection of the right middle lobe for her giant
      lung cyst under general anesthesia. Second case was an eight-month-old male who
      underwent thoracoscopic resection of his left mediastinal tumor under general
      anesthesia. One-lung anesthesia was successfully established with Fogarty
      catheters for both cases. Size of the catheter and its balloon was decided
      beforehand by measuring the diameter and length of the trachea and both bronchi
      based on the image obtained from computerized tomography (CT) in both cases.
      Therefore, surgical field was well visible during operation. There was no
      accidental episode in perioperative period. Bronchoscopy with ultra-thin
      fiberscope and X-ray fluoroscopy is useful to decide the position of Fogarty
      catheter and its balloon. Our means is recommendable for maintenance of one-lung
      anesthesia in infant.

PMID- 12229137
TI  - [Pretreatment with lidocaine accelerates onset of vecuronium-induced
      neuromuscular blockade].
AB  - The purpose of this study was to investigate the effect of pre-treatment with
      lidocaine on the onset of vecuronium-induced neuromuscular block in a randomized,
      double-blinded trial. Thirty-one patients were randomly allocated to one of two
      groups according to the agents administrated 3 min prior to vecuronium injection;
      Group C, normal saline 0.75 ml.kg-1 and Group L, 2% lidocaine 1.5 mg.kg-1.
      Anesthesia was induced with propofol 1.5 mg.kg-1 followed by continuous infusion
      at 8 mg.kg-1.hr-1. Neuromuscular blockade was evaluated with accelerometry, which
      measured a train-of-four (TOF) pattern of abductor policies muscle. The
      disappearance of the first response in TOF was regarded as onset of neuromuscular
      block. Changes in systolic and diastolic arterial pressure (SBP, DBP) and heart
      rate (HR) were measured before and after tracheal intubation. Times to onset of
      neuromuscular blockade induced by vecuronium in Group L and Group C were 115 +/-
      20 sec and 174 +/- 45 sec, respectively. After tracheal intubation, SBP, DBP and
      HR in both groups increased compared with those before tracheal intubation, but
      the changes were not significant. Changes in SBP, DBP and HR did not differ
      between Group L and Group C. The mechanisms by which lidocaine reduced the time
      to onset of neuromuscular block caused by vecuronium could not be clarified from
      our study, but this may be related to pre- and post-junctional effects of
      lidocaine at neuromuscular junction. In conclusion, administration of lidocaine
      prior to tracheal intubation reduces the time to onset of neuromuscular block
      caused by vecuronium, but does not attenuate changes in blood pressure and heart
      rate caused by tracheal intubation.

PMID- 12229138
TI  - [Anesthetic factors that influence pH of neonatal umbilical artery from mothers
      in severe gestosis during cesarean section under sevoflurane anesthesia].
AB  - Twenty-two patients complicated with severe gestosis underwent cesarean section.
      General anesthesia was induced with intravenous thiopental and suxamethonium and
      maintained with sevoflurane below 1.5% with 40-50% oxygen and 50-60% nitrous
      oxide. Mean artery pressure at and after the induction as well as at the
      delivery, expired maternal sevoflurane concentrations at the delivery and neonate
      birth weight were measured for statistical analyses in relation with neonates pH
      of umbilical artery. Mean artery pressure at the delivery and neonates birth
      weight influence neonates pH of umbilical artery.

PMID- 12229139
TI  - [The use of propofol combined with nitrous oxide and fentanyl in anesthetic
      management of a patient with mitochondrial encephalomyopathy].
AB  - A 49-year-old female with mitochondrial encephalomyopathy underwent surgery for
      implantation of an artificial cochlear device. She had some characteristic
      clinical features, including muscle weakness, deafness and dementia. Anesthesia
      was induced with 5 mg.kg-1 of propofol, and the trachea was intubated without a
      muscle relaxant. The patient was mechanically ventilated also without a relaxant,
      and anesthesia was maintained with a continuous infusion of 4-8 mg.kg-1.hr-1 of
      propofol, a bolus injection of 50-100 micrograms of fentanyl, and nitrous oxide
      (66%) in oxygen (33%). Bispectral index (BIS) was monitored and maintained at
      approximately 40. No cardiovascular instabilities or increase in plasma lactate
      concentration were observed during surgery. The patient had a smooth recovery
      from the propofol anesthesia, and the BIS value returned to the pre-anesthetic
      level 10 min after completion of the anesthesia, suggesting that the use of
      propofol is a safe means for inducing and maintaining anesthesia in patients with
      mitochondrial encephalomyopathy.

PMID- 12229140
TI  - [A case of postoperative palsy of the brachial plexus and facial nerve caused by
      use of cervical collar during lung surgery].
AB  - We report a case of palsy of the brachial plexus and facial nerve manifested
      after surgery for lung cancer in a 77-year-old female who also had a
      retroodontoid pseudotumor. Lobectomy was conducted with the patient in a left
      lateral position. For the purpose of cervical stabilization, the orthopedic
      surgeon recommended the use of a cervical collar. During the operation, both of
      her arms were abducted at nearly 80 degrees. On the second postoperative day, the
      patient complained of sensory disturbances in the lateral area of her left
      brachium and forearm, which are innervated by the 5th and 6th cervical spinal
      nerves from the brachial plexus. She also complained that she could not abduct
      and flex her left shoulder, and could not flex her left elbow at all.
      Simultaneously, facial nerve palsy was observed in her left lower lip. During the
      operation, her shoulders were forcibly rotated internally and were extremely
      abducted, resulting in a narrowed distance between the lower jaw and the shoulder
      and stretching of the brachial plexus. Under this situation, the cervical collar
      was pressing strongly upon her neck and lower jaw, which might have produced the
      brachial plexus complication and facial nerve palsy.

PMID- 12229141
TI  - [Airway management in tracheal stenosis caused by malignant goiter].
AB  - We report a case of malignant goiter with severe tracheal stenosis. The patient
      was a 61-year-old female, who had orthopnea on admission. Radiological
      examinations revealed a tracheal stenosis extending from 4.5 cm to 8 cm below the
      glottis; the smallest caliber being 5 mm. On the seventh day after admission, the
      patient complained of dyspnea even while sitting. An emergency tracheotomy was
      scheduled. While the patient was awake in a sitting position, a fiberscope was
      inserted endotracheally to confirm the intact inner surface of the trachea, and
      then an armored endotracheal tube (outer diameter 9.2 mm, inner diameter 6.5 mm)
      was inserted. Unexpectedly, the tube could be advanced through the stenosis
      without resistance. After induction of general anesthesia, the patient was placed
      in a supine position, and a tracheotomy was performed. This case demonstrates
      that, while intubation of the trachea through a stenosis is sometimes dangerous,
      it may be indicated when the inner surface of the trachea is intact and a tube
      with an inner diameter greater than 5 mm can then be placed.

PMID- 12229142
TI  - [A case report of hemidiaphragmatic paresis caused by interscalene brachial
      plexus block].
AB  - A 76-yr-old woman was scheduled for left upper extremity orthopedic procedure.
      Preoperative examinations were within normal limits except forced vital capacity.
      Interscalene brachial plexus block with 0.25% bupivacaine 15 ml, was performed
      under general anesthesia. Her intraoperative course was uneventful. She, however,
      complained of the dyspnea after removal of a tracheal tube, and Spo2 dropped to
      89%. A chest X-ray demonstrated the elevation of hemidiaphragm. She was diagnosed
      as ipsilateral hemidiaphragmatic paresis, treated with oxygen inhalation under
      deep breathing for approximately one hour, and then transferred to the common
      ward. We conclude that respiratory movement should be carefully observed
      following interscalene brachial plexus block especially in geriatric patients.

PMID- 12229143
TI  - [Anesthetic management of a patient with dentato-rubro-pallido-luysian atrophy].
AB  - This report may be the first case of perioperative management in a patient with
      dentato-rubro-pallido-luysian atrophy (DRPLA). A 19-yr-old man with DRPLA was
      admitted for recurrent aspiration pneumonia. Medications included phenobarbital,
      carbamazepine and clonazepam. The planned surgical procedure was tracheostomy and
      tracheoesophageal separation. He recovered from these procedures uneventfully.
      Two months later, however, he was readmitted for plastic surgery of narrowing
      tracheostoma. All of these procedures were performed under general anesthesia,
      induced using propofol (or thiamylal) and vecuronium, and maintained with
      sevoflurane. Thiamylal, propofol and benzodiazepines were effective in the
      prevention of myoclonus-like seizure. No adverse effects of muscle relaxant were
      observed.

PMID- 12229144
TI  - [Remarkable rightward shift of the mediastinum during a urological operation in
      the left kidney position--a case report].
AB  - Mediastinal rightward shift without involving cardiovascular collapse and dyspnea
      occurred after a left nephroureterectomy. An 86-year-old female (height, 142 cm;
      weight, 53 kg) with ureteral cancer was scheduled for an elective
      nephroureterectomy. Preanesthetic electrocardiogram revealed supraventricular
      premature contractions and sinus tachycardia (116 beats.min-1) and preanesthetic
      chest X-ray film revealed cardio-thoracic ratio of 60% and pleural adhesion of
      the right apex of the lung. Anesthesia was maintained with a combination of
      inhalation anesthetics (oxygen, nitrous oxide and sevoflurane) and thoracic
      epidural lidocaine. Artificial ventilation was used during the anesthesia. The
      operation was uneventful. A chest radiograph taken at the end of the operation
      demonstrated a large mass-like shadow in the right field of the lung. However,
      dyspnea or cardiovascular collapse was not observed. The vesicular sounds were
      auscultated in the left lung field. Results of arterial blood gas analysis during
      spontaneous respiration were within normal ranges. A CT scanning of the chest
      showed that the great vessel and the heart had been in the right thoracic cavity.
      Therefore, we considered that a rightward mediastinal shift had occured during
      the operation.

PMID- 12229145
TI  - [Anesthetic management of two patients with the history of SMON].
AB  - Patients of subacute myelo-optico-neuropathy (SMON) suffer from neurological
      disorders for a long time. The authors report anesthetic management of two
      patients with SMON. One patient was a 82-year-old woman suffering from SMON for
      49 years. Sensory examination revealed numbness and hypesthesia in the both lower
      extremities. She underwent open reduction for femoral neck fracture. The other
      patient was a 91-year-old man suffered from SMON for 31 years. Sensory
      examination revealed weakness of leg muscles. He underwent transurethral
      resection of prostate. We chose general anesthesia for both patients instead of
      spinal anesthesia because of reported complications related to spinal anesthesia
      in patients with the disease. Intraoperative courses were uneventful and there
      were no neurological deteriorations postoperatively in both patients. One of the
      chief symptoms of patients with SMON is numbness of the lower extremity.
      Therefore patients of SMON may feel uncomfortable to the numbness by spinal or
      epidural anesthesia. This is the main reason we recommend general anesthesia for
      patients with SMON.

PMID- 12229146
TI  - [Fiberoptic tracheal intubation aided by jaw lifting in a patient with an
      epiglottic cyst].
AB  - Epiglottic cyst is known to cause difficult intubation. We report a patient with
      an epiglottic cyst whose trachea was successfully intubated with the aid of
      fiberoptic bronchoscopy combined with the jaw lift maneuver. A 29-year-old
      patient was scheduled for lumbar disk hernia surgery. On the first occasion,
      surgery was cancelled since the patient was unexpectedly found to have an
      epiglottic cyst and tracheal intubation was not possible. Two weeks later,
      nasotracheal intubation guided by fiberoptic bronchoscopy under conscious
      sedation was planned. On the first attempt of bronchoscopy, the glottic view was
      obscured by the cyst displacing the epiglottis posteriorly. Next, we applied the
      jaw lift maneuver in conjunction with bronchoscopy. The maneuver improved the
      glottic view by clearing the epiglottis from the posterior pharyngeal wall and
      the patient's trachea was successfully intubated. Jaw lifting could be a useful
      adjunct to fiberoptic bronchoscopy for tracheal intubation in patients with
      epiglottic cysts.

PMID- 12229147
TI  - [Anesthetic management of a neonate with laryngotracheoesophageal cleft and
      tracheoesophageal fistula].
AB  - Laryngotracheoesophageal cleft (LTEC) is an extremely rare congenital anomaly
      characterized by an absence of all or a part of the tracheoesophageal septum
      producing an abnormal communication between the trachea and esophagus, and is
      often difficult to be diagnosed. A 2-day-old male baby was tentatively diagnosed
      as tracheoesophageal fistula type Gross C, and underwent gastrostomy. The trachea
      was intubated before anesthetic induction. When a balloon of gastrostomy catheter
      was inflated, the lung could not be ventilated. After extubation of endotracheal
      tube and removal of gastrostomy catheter, the lung could be ventilated with mask.
      When endotracheal tube was intubated again, the lung could not be ventilated at
      all. Thus the surgery was performed under mask ventilation. Endoscopic
      examination performed 2 weeks later gave diagnosis of LTEC type 3. It is likely
      that the endotracheal tube might have been advanced into the end of the esophagus
      due to absence of the tracheoesophageal septum. In spite of a rare disease, LTEC
      should be considered as an extreme case of transesophageal fistula with a high
      risk of difficult airway.

PMID- 12229148
TI  - [Continuous epidural analgesia with intensive monitoring of cardiovascular system
      for vaginal delivery in a patient with Marfan's syndrome].
AB  - We report here the management of labor for a 33-year-old woman with Marfan's
      syndrome. She was diagnosed as Marfan's syndrome at the age of 5 and experienced
      corrective surgery for abdominal aortic aneurysm at 28 years of age. As there was
      no progression of cardiovascular lesion, she was allowed to be pregnant. She was
      planned to proceed with vaginal delivery, since she was in trouble of circulation
      during her gestational period. In order to prevent catastrophe such as aortic
      dissection or aortic regurgitation elicited by hypertension related with labor
      pain, we performed continuous epidural anesthesia to control labor pain under the
      invasive blood pressure monitoring. Two epidural catheters were inserted into the
      epidural space via the L 2-3 and the L 5-S 1 intervertebral space, and mixed
      solutions containing both 0.125% bupivacaine and 0.0002% fentanyl were
      administered continuously. After 7 hours and 47 minutes from the start of her
      labor, she delivered her baby vaginally with the aid of forceps technique due to
      attenuated abdominal muscle activity. No cardiovascular mishaps occurred during
      her labor and she was discharged 6 days after the delivery. Thus, continuous
      epidural anesthesia with intensive monitoring of circulation may be useful for
      vaginal delivery in a patient with Marfan's syndrome by avoiding cardiovascular
      complications due to labor pain.

PMID- 12229149
TI  - [Anesthetic management for thoracoscopic partial lobectomy in a patient with one
      lung].
AB  - A 58-year-old man whose right lung had been removed due to lung cancer underwent
      thoracoscopic partial lobectomy of the left lung. Anesthesia was maintained with
      intravenous propofol and thoracic epidural block. During the surgery,
      respirations were controlled by high frequency jet ventilation. There was no
      intraoperative hypoxia. The postoperative course was uneventful.

PMID- 12229150
TI  - [Tuberculosis detected after emergency cesarean section].
AB  - A 29-year-old woman at 37 weeks of gestation was brought to our hospital as an
      emergency patient complaining of severe cough, hemoptysis and dyspnea. On
      arrival, we suspected that she was suffering from bronchial asthma or pulmonary
      embolism, but were unable to improve her respiratory condition. The decision was
      made to terminate gestation immediately and an emergency cesarean section was
      performed under spinal anesthesia. Postoperatively diagnosis of tuberculosis was
      made. Fortunately, there was no intramural tuberculous infection. She was a
      nurse. Nurses are twice as likely as the general public to contract tuberculosis.
      Medical workers must keep in mind that they may be infected with tuberculosis and
      they could also become the source of infection of tuberculosis. It is important
      to rule out tuberculosis when a patient, particularly a medical worker, complains
      of severe cough, hemoptysis and dyspnea.

PMID- 12229151
TI  - [Training of epidural anesthesia with pressure-guided method in pediatric
      patients].
AB  - Epidural anesthesia in pediatric patients has become popular, and some useful
      techniques have been introduced. We use the pressure-guided method to identify
      the epidural space. This method enables us to visualize, on the monitor, the
      pressure change as the needle advances. With this method, we, including even a
      new resident in anesthesia, can identify the epidural space objectively and
      safely. A pressure transducer with saline-filled tubing is connected to a Tuohy
      needle. As the needle advances, the pressure rises gradually. As soon as the
      needle enters the epidural space, the pressure suddenly decreases and
      synchronizes with the heart beats. In the first 10 months after I started working
      as a resident in anesthesia, I performed 16 pediatric epidural anesthesias
      successfully under the direction of the anesthetic specialist. I would like to
      emphasize that I was able to perform epidural anesthesia safely at the thoracic
      level (T 11 x 12) even in the newborn (body weight 3400 g). The pressure-guided
      method enables us, even a new resident, to accomplish epidural anesthesia at
      thoracic level in newborn.

PMID- 12229152
TI  - [A simple lightweight device for measurement of low hemoglobin concentrations:
      the Hemo Cue Low Hemoglobin Photometer].
AB  - To determine low hemoglobin concentrations in the washed fluid is useful for
      calculation of blood loss and that in the supernatant is also useful for
      evaluation of hemolysis during extracorporeal circulation or in the blood
      preparations. The HemoCue Low Hemoglobin Photometer is a new lightweight device,
      which is easily movable anywhere and is able to determine hemoglobin
      concentration in low ranges (0.03-3.00 g.dl-1). We investigated the accuracy and
      reliability of the HemoCue Low Hemoglobin Photometer. Blood samples were diluted
      with saline containing heparin into six tubes. The hemoglobin concentrations of
      each diluted sample were measured by the HemoCue Low Hemoglobin Photometer, and
      were compared with the calculated values. A high positive correlation was found
      between the values measured by the HemoCue Low Hemoglobin Photometer (Y) and the
      calculated values (X); Y = 1.047 X, r = 0.999, P < 0.0001. It took only 11-54
      seconds (mean value: 31.4 seconds) for the measurement. It is concluded that the
      HemoCue Low Hemoglobin Photometer is a reliable and useful device for measurement
      of low hemoglobin concentration.

PMID- 12229153
TI  - [Current topics of surgical treatments for advanced gallbladder carcinoma. I.
      Introduction].

PMID- 12229154
TI  - [Surgical treatment for advanced gallbladder cancer: indications and
      limitations].
AB  - We have aggressively performed extensive surgery including major liver resection
      for advanced gallbladder cancer since 1979. The 5-year survival rates for stage
      IVa and IVb patients after curative resection were 19% and 6%, respectively.
      Seven patients in the stage IVa group (n = 69) and one in stage IVb (n = 16) have
      survived for more than 5 years. The hospital mortality rate including all deaths
      within and over 30 days of curative operation for stage IV gallbladder cancer was
      19%. Although radical resection is the only treatment of choice for advanced
      gallbladder cancer to obtain long-term survival, there are serious problems in
      extensive surgery. The most important issue is reduction of the hospital
      mortality rate. Elucidation of the clinical and molecular characteristics leading
      to potential long-term survival and development of new strategies for the
      treatment of recurrent tumors are also important issues.

PMID- 12229155
TI  - [S4 S5 subsegmentectomy of the liver for gallbladder carcinoma].
AB  - Although innovations have occurred in imaging technology and surgical techniques,
      carcinoma of the gall-bladder still has a poor prognosis. Since the 1960s, we
      have performed extended cholecystectomy in patients with gallbladder cancer.
      Extended cholecystectomy is a safe and common treatment for advanced cancer, but
      the extent of necessary hepatic resection has not been established. In 2000, we
      reported that the gallbladder veins infused into the intrahepatic portal venous
      branch, mostly at P4 and P5(96.7%). Based on those results, we now perform
      resection of the lower part of segment 4(S4a) and segment 5 for advanced cancer
      with subserosal invasion and/or negligible direct invasion to the parenchyma of
      the liver. S4aS5 subsegmentectomy is thought to have a clear advantage over
      extended surgical margins. This procedure can remove almost all the area perfused
      by the gallbladder veins and as a results, it may also remove latent and occult
      metastatic foci. The steps in the procedure are as follows: 1) lymph nodes
      cleaning of the posterior of the pancreas head; 2) skeletonization of the
      hepatoduodenal ligament; 3) identification and ligation of the lower branch of
      P4; 4) identification of the boundary between the anterior and posterior segment;
      and 5) hepatic resection with the plate of the gallbladder. Since 1991, we have
      performed S4aS5 subsegmentectomy in 12 patients with gallbladder cancer. Although
      the follow-up period is short, it is thought that the outcome of this procedure
      is better than that of extended cholecystectomy because of the low mortality and
      morbidity rates.

PMID- 12229156
TI  - [Indication and operative techniques of extended right hepatic lobectomy for
      advanced gallbladder cancer].
AB  - Gallbladder cancer extends directly to the hepatic hilum and/or the right portal
      pedicle in the hepatic hilum type and the bed and hilum type of disease. Extended
      right hepatic lobectomy (ERHL), caudate lobectomy, lymph node dissection, and
      biliary reconstruction are necessary for radical resection of the tumor. It was
      previously thought that this extensive surgery carried high risk, with a hospital
      death rate of 20%, and had little survival benefit. However, it is now feasible
      with lower risk due to improvement in biliary decompression techniques,
      prevention of intrahepatic segmental cholangitis, introduction of preoperative
      portal embolization, etc. Long-term survival has been achieved after surgery
      unless there is hepatic, peritoneal, or paraaortic metastasis. Hilar hepatic
      involvement is more advanced in gallbladder cancer than in bile duct cancer, and
      portal vein resection and reconstruction are inevitable. All six such patients in
      our department over the past two years underwent concomitant portal
      reconstruction and have survived postoperatively.

PMID- 12229157
TI  - [Significance of aggressive lymph node dissection in advanced gallbladder
      carcinoma].
AB  - Although aggressive lymph node dissection has been performed in gallbladder
      carcinoma as well as in other carcinomas of the alimentary tract, there is no
      definitive evidence of the efficacy of extended lymph node dissection. However,
      extensive lymph node metastasis is well known in advanced carcinoma of the
      gallbladder. From the viewpoint of the balance between radicality and safety in
      surgery, wider lymph node dissection consisting of the lymph nodes in the
      hepatoduodenal ligamentum and parapancreatic area is recommended in selected
      patients who hare no involvement of the paraaortic lymph nodes. Complete
      dissection of the superior mesenteric lymph nodes with pancreaticoduodenectomy is
      unlikely to result in cure.

PMID- 12229158
TI  - [Significance of resecting the head of the pancreas for the treatment of
      gallbladder cancer from the perspective of surgical results and mode of lymph
      node metastasis].
AB  - The significance of resecting the head of the pancreas was clinicopathologically
      investigated, predominantly by examining the mode of lymph node metastasis, in
      patients with gallbladder cancer. Of 60 patients who underwent resection of
      gallbladder cancer, 24 patients (40.0%) had lymph node metastasis. The breakdown
      of lymph node metastases was as follows: 12b (24.0%), 16 (21.7%), 13 (17.1%), 8
      (12.2%), 12c (12.0%), 12p (8.0%), and 6 (6.3%). Of 45 patients with advanced
      gallbladder cancer, 14 patients survived more than 5 years after surgery. In the
      absence of lymph node metastasis, there were some long-term survivors following
      D0 dissection, gallbladder resection, or liver bed resection. However, all five
      long-term survivors with lymph node metastasis underwent S4aS5 resection combined
      with pylorus preserving pancreatoduodenectomy (PPPD) and D3 dissection. Seven
      patients had number 13 lymph node metastasis, and only two n2 patients who
      underwent S4aS5 resection combined with PPPD and D3 dissection, survived more
      than 5 years. There were no long-term survivors with n3 lymph node metastasis. Of
      the 50 patients who underwent curative resection, 13 patients experienced
      recurrence: in the liver in six patients, in the peritoneum in four patients, in
      the lymph nodes in four patients, in the bone in two patients, in the lung in one
      patient, and local in one patient (including duplicate cases). Of the four
      patients with lymph node recurrence, two demonstrated number 12 and/or number 13
      lymph node metastasis at the time of surgery and underwent bile duct-conserving
      D2 dissection, although cancer recurred in the head of the pancreas, probably due
      to recurrence in number 13 lymph node. Extensive resection including resection of
      the head of the pancreas was therefore effective in patients with up to n2 lymph
      node metastasis as long as the cancer could be completely sected.

PMID- 12229159
TI  - [Postoperative complications and management in the surgical treatment for
      advanced gallbladder carcinomas].
AB  - Surgical treatment for advanced gallbladder carcinoma must be based on the extent
      of the cancer. There are various patterns of cancer spread in advanced
      gallbladder carcinoma. In cases with hepatic involvement, liver bed resection,
      hepatic segment Iva + V resection, extended right hepatectomy, or right
      trisegmentectomy can be selected. In cases with biliary involvement, extended
      right hepatectomy, pancreaticoduodenectomy, or combined vascular resection can be
      performed. In cases with gastrointestinal involvement, the involved intestine can
      be resected with cholecystectomy and bile duct resection. Surgical morbidity
      rates after surgical treatment for advanced gallbladder carcinoma have been
      reported to be very high at about 50%, and surgical mortality rates are 7-20%.
      After extended hepatic resection, surgical mortality rates reach to 30-43%.
      Hepatopancreaticoduodenectomy (HPD) has a high surgical mortality rate of 25-33%,
      and combined vascular resection also has a high mortality of 13-67%. To decrease
      these high morbidity and mortality rates, limited hepatic resection and
      preoperative portal embolization in hepatic resection, two-stage
      pancreaticoduodenectomy in HPD, and preservation of the hilar plate at bile duct
      resection in right hepatic artery resection may be useful. Surgical indications
      and the choice of operative procedures should be very carefully considered in
      patients with advanced gallbladder carcinoma because of its high surgical
      morbidity and mortality rates.

PMID- 12229160
TI  - [Study of cut-off values for orotate phosphoribosyl transferase (OPRT) in
      colorectal cancer using maximal chi 2 values].

PMID- 12229161
TI  - [Fulminant hepatitis and late onset hepatic failure (LOHF) in Japan].

PMID- 12229162
TI  - [Medical treatment of fulminant hepatitis].

PMID- 12229163
TI  - [Liver transplantation for fulminant hepatic failure].

PMID- 12229164
TI  - [Is p53 immunohistochemistry useful for optimal decision for treatment of
      polypoid lesions in ulcerative colitis?].
AB  - BACKGROUND: Usefulness of p53 staining for the differentiation between adenoma
      and DALM has been reported recently, so recognizable lesions stained positively
      can be diagnosed as DALMs. For the cases with DALMs, total colectomy has been
      thought to be necessary. METHODS: Immunohistochemical staining for p53 was
      performed in 4 adenocarcinomas and 4 adenomas in ulcerative colitis. RESULTS:
      Three carcinomas and 3 adenomas were positive. One carcinoma (protruded mucosal
      cancer) and 3 adenomas (1 flat elevated lesion and 2 laterally spreading tumors)
      stained positively for p53 were treated only by polypectomy or local excision.
      The patients have been under surveillance for periods ranging from 1 to 10 years,
      during which no metachronous dysplasia has developed. CONCLUSIONS: These findings
      suggest that some groups of the polypoid lesions can be resected locally even if
      stained positively by p53 immunohistochemistry.

PMID- 12229165
TI  - [CT evaluation of infectious colitis].
AB  - Computed tomography (CT) is useful for evaluating the diagnosis of
      gastrointestinal disease, such as infectious colitis, in patients with severe
      pain and bloody diarrhea. During the 7 years between November 1993 and October
      2000, 34 patients with infectious colitis (18 male, 16 female; mean age 42 +/- 19
      yrs), received emergency CT and colonoscopy because of severe abdominal pain and
      dysentery. The following organisms were isolated: pathogenic Escherichia coli
      (12), 6 of which were O157:H7 (O-157), Salmonella species (11), Campylobacter
      species (5), Vibrio parahaemolyticus (3), Yersinia enterocolotica (2) and
      Shigella species (1). Thickening of the intestinal wall greater than 10 mm was
      seen in the ascending colon in the 6 cases with E. coli O 157, in 5/11 cases with
      Salmonella, 4/5 with Campylobacter and 1/6 with non-O157 pathogenic E. Coli.
      Marked intestinal wall thickening, greater than 20 mm, was seen in the ascending
      colon of the 4 of the patients with an O-157 infection. In all patients with O
      157 colitis, slight ascites was noted in the pelvic space. In additions, ascites
      was also seen in 3/13 patients with Salmonella and 1/5 patients with
      Campylobacter colitis. The CT findings, in the patients with infectious colitis,
      are non-specific but knowledge and recognition of the findings will help in
      patient evaluation and proper treatment.

PMID- 12229166
TI  - [Herpes esophagitis presenting upper gastrointestinal bleeding: report of a
      case].

PMID- 12229167
TI  - [A case of GIST with rapid growth caused by internal hemorrhage].

PMID- 12229168
TI  - [An autopsy case of an old-aged mesenteric rhabdomyosarcoma].

PMID- 12229169
TI  - [Successful treatment for erythema nodosum and peripheral arthritis associated
      with ulcerative colitis by granulocyte and monocyte apheresis: a report of a
      case].

PMID- 12229170
TI  - [A case of pneumatosis cystoides intestinalis associated with gastric carcinoma
      and colonic carcinoma].

PMID- 12229171
TI  - [A case report of arterial embolization of common hepatic arterial aneurysm].

PMID- 12229172
TI  - [A case of primary sclerosing cholangitis associated with chronic pancreatitis
      and Sjogren's syndrome].

PMID- 12229173
TI  - [A case of hemorrhagic cholecystitis during anticoagulant therapy, following
      surgery of aortic valve replacement, mitral valve plasty and tricuspid valve
      plasty].

PMID- 12229174
TI  - [A case of secondary sclerosing cholangitis with jaundice due to bile duct stones
      during 18 years].

PMID- 12229175
TI  - [A case of secondary iliopsoas abscess induced by acalculous cholecystitis].

PMID- 12229176
TI  - [Clinical study of six cases of pyourachus at our hospital].
AB  - We encountered 6 patients with pyourachus (male, 1; female, 5) who ranged in age
      from 17 to 58 years (mean, 41 years) during the 7 years from 1993 to 1999. Three
      of them had a history of gynecological surgery, and 2 had a history of
      appendectomy. Improvement was observed in one patient with conservative therapy
      alone, but the other 5 patients underwent surgery. Preoperatively, 2 patients
      underwent drainage, one of them through the umbilicus, and the other through a
      position on the midline percutaneously. Pathological examination in the 5
      patients revealed no evidence of cancer. With reference to postoperative
      complications, adhesive ileus was recognized in 1 case one year postoperatively
      but no other complications were noted in the other 5 cases. No evidence of
      recurrence has been seen in any of these patients to date.

PMID- 12229177
TI  - Orthotopic ileal neobladder reconstruction using a modified Goodwin method:
      functional outcome in 37 patients.
AB  - Since 1996, we have been using a modified Goodwin technique for orthotopic ileal
      neobladder replacement. We report on the surgical technique and the voiding
      function of ileal neobladder in 37 patients. A small bowel segment, 50 cm in
      length, was resected 20 cm proximal to the ileocecal valve. The small bowel loops
      were then arranged in a U shape. Vodiing function was evaluated in terms of
      voiding pattern, continence and urodynamic study. The mean follow-up period was
      18 months (range 3 to 64). The mean maximum neobladder pressure in the storage
      phase was 15 cm water at 6 months, 12 at 12 months, and 7 at 24 months. The mean
      maximal urethral closed pressure was 52 cm water at 6 months, 51.7 at 12 months,
      and 66 at 24 months. The mean maximal urinary flow rate was 16.2 ml per second at
      6 months, 17.6 at 12 months, and 20.8 at 24 months. The mean maximal neobladder
      capacity was 300 ml at 6 months, 302 ml at 12 months, 382 ml at 24 months. Among
      the 37 patients, 30 remained completely dry day and night. Three patients were
      incontinent only during the nighttime, and required only one pad. Four patients
      were wet day and night, and required 2 pads daily. Our results indicate that the
      modified Goodwin method appears to be an excellent technique for ileal neobladder
      replacement following cystectomy and seems successful in producing balanced
      voiding dynamics.

PMID- 12229178
TI  - Nephrostomy tract tumor seeding following percutaneous manipulation of a renal
      pelvic carcinoma.
AB  - We report a case of nephrostomy tract tumor seeding following percutaneous
      pyeloscopic manipulation of a renal pelvic carcinoma. To our knowledge, this is
      the second reported case of such a lesion surrounding the nephrostomy tract.
      Percutaneous pyeloscopic treatment carries a potential risk of local tumor
      spillage and implantation in the nephrostomy tract.

PMID- 12229179
TI  - [A case of neuropathic bladder with inflammatory pseudotumor of the bladder].
AB  - A 36-year-old woman was referred with urinary incontinence and recurrent episodes
      of pyelonephritis. Two years prior to her visit, she underwent transurethral
      resection of a bladder tumor, 5 cm in diameter. Total cystectomy was suggested,
      as the initial diagnosis was sarcoma. Close re-evaluation of the pathological
      specimen lead to the final diagnosis of a benign inflammatory pseudotumor of the
      bladder as the tumor consisted of smooth muscle cells with white blood cell
      infiltration but without mitotic figures. The tumor disappeared during the follow
      up period. A cystography revealed bilateral vesicoureteral reflux with marked
      trabeculated bladder. A cystometry showed loss of bladder sensation and a low
      compliance bladder without detrusor contraction. Neurological examination and a
      magnetic resonance imaging of the spinal cord failed to prove the presence of
      definite neurological abnormalities. She was finally diagnosed with neuropathic
      bladder of unknown origin. In this case, she had been suffering from recurrent
      cystitis about 6 years before the resection of bladder tumor and it was suggested
      that the occurrence of the inflammatory pseudotumor of bladder would be related
      with chronic urinary tract infection due to neuropathic bladder. Urinary
      incontinence and urinary tract infection were controlled successfully with clean
      intermittent self-catheterization and adequate administration of antimicrobial
      drugs. Vesicoureteral reflux was treated with injection of GAX collagen into the
      ureteral orifices. No tumor recurrence has been found up to the present time, 5
      years after the resection of bladder tumor.

PMID- 12229180
TI  - [Intraarterial neoadjuvant chemotherapy with cisplatin effective against
      neuroendocrine carcinoma of the urinary bladder: a case report].
AB  - A 68-year-old male was admitted to our hospital with a complaint of asymptomatic
      gross hematuria. On physical examination, a huge mass was palpable in the lower
      abdomen. Computed tomography revealed a huge mass, 12 x 10 cm in size, in the
      urinary bladder and no metastatic lesions. The value of serum neuron specific
      enolase (NSE) was 32 ng/ml (normal range: 0-10 ng/ml). Histopathological and
      histochemical studies revealed neuroendocrine carcinoma which was positive for
      NSE, chromogranin A, S-100 and cytokeratin. He underwent neoadjuvant ballon
      occluded arterial infusion (BOAI) chemotherapy with cisplatin (CDDP). Total
      cystectomy and ileal conduit formation were performed at the preoperative
      diagnosis of T3N0M0. Examination of the resected specimen indicated a
      pathologically complete response and he was discharged. The patient is still
      alive with no evidence of any recurrence at 3 months after the operation. This
      case suggests that treatment with combined total cystectomy and neoadjuvant BOAI
      chemotherapy is effective against neuroendocrine carcinoma of the urinary
      bladder.

PMID- 12229181
TI  - [Successful salvage chemotherapy with gemcitabine, etoposide and cisplatin for
      metastatic ureteral cancer: a case report].
AB  - A 35-year-old man who had undergone nephroureterectomy and a single cycle of
      adjuvant MVAC chemotherapy for the left ureteral cancer was referred our clinic
      for the treatment of paraaortic lymph node metastases. Following histologic
      confirmation of transitional cell carcinoma by computed tomography (CT) guided
      biopsy, we treated him with combination chemotherapy consisting of ifosfamide, 5
      fluorouracil, etoposide and cisplatin. After 5 cycles of chemotherapy complete
      remission was obtained. Six months later, however, metastases recurred in the
      left supraclavicular and paraaortic lymph nodes. Thus, we treated him with a new
      combination chemotherapy comprising gemcitabine, etoposide and cisplatin which
      was approved as a phase I study by the institutional review board. Although he
      was the first patient enrolled in the study and received the minimum dose of
      gemcitabine (level 1), complete remission was again achieved. Adjuvant
      radiotherapy of 40 Gy was given to the metastatic sites. He has been well without
      evidence of disease for 12 months.

PMID- 12229183
TI  - [A case of acute spongiositis with diabetes mellitus].
AB  - We report a case of acute spongiositis with diabetes mellitus. A 63-year-old man
      with a 7-year history of diabetes mellitus was admitted to our hospital
      complaining of perineal pain and pyrexia. Physical examinations revealed
      induration and tenderness of the corpus spongiosum, but no signs of rubor or
      erosion. A laboratory investigation showed leukocytosis (12,000/microliter), an
      elevated level of C-reactive protein (3.38 mg/dl) and hyperglycemia (532 mg/dl).
      Pyuria and bacteriuria were absent. Magnetic resonance imaging (MRI) yielded
      abscess-like lesion of the corpus spongiosum. Culture of the aspirated specimen
      demonstrated B-hemolytic streptococci. Treatment with antibiotics and insulin
      resolved leukocytosis and tenderness of corpus spongiosum. He left the hospital
      on the 23rd day after admission and no evidence of recurrence of the spongiositis
      was found for 1 year after discharge.

PMID- 12229182
TI  - [Bilateral laparoscopic adrenalectomy in ACTH-independent macronodular adrenal
      hyperplasia: a case report].
AB  - We report a case of ACTH-independent macronodular adrenal hyperplasia (AIMAH). A
      62-year-old man was admitted to our hospital for further examination of obesity
      and diabetes mellitus. He was diagnosed with Cushing's syndrome by
      endocrinological examinations, and computed tomography and magnetic resonance
      imaging findings revealed nodular hyperplasia in bilateral adrenal glands,
      suggesting its etiology to be AIMAH. We underwent simultaneous bilateral
      laparoscopic adrenalectomy. A preoperative diagnosis of AIMAH was confirmed by
      histological examination of both adrenal glands, weighing 21 g (right) and 16 g
      (left). The postoperative course was uneventful. We believe that simultaneous
      bilateral laparoscopic adrenalectomy is feasible, safe, and results in minimal
      postoperative morbidity for the treatment of AIMAH.

PMID- 12229184
TI  - [A case of renal cell carcinoma in a horseshoe kidney].
AB  - A-50-year-old patient visited our hospital to have further examination for left
      renal mass. Drip infusion pyelography revealed a cluster of calculi in the upper
      pole of the left kidney. Computed tomography and magnetic resonance imaging
      revealed a heterogeneous mass on the left side of a horseshoe kidney. Left
      nephrectomy was performed through an abdominal transperitoneal approach. An
      operation for dividing isthmus was simultaneously done using a microwave tissue
      coagulator. Histopathological findings showed grade 1 > 2, pT1aN0M0, clear cell
      subtype, renal cell carcinoma. Convalescence was uneventful and the patient was
      free of tumor at one year postoperatively.

PMID- 12229185
TI  - [Local recurrence of liposarcoma of the spermatic cord 6 years after orchiectomy:
      a case report].
AB  - A 78-year-old man had undergone high inguinal orchiectomy because of a tumor of
      the right spermatic cord. Pathological diagnosis was pleomorphic liposarcoma
      according to the WHO classification. Adjuvant therapy was not performed because
      of advanced age. Six years later, he consulted our hospital with the chief
      complaint of asymptomatic swelling of the right scrotal region. Local recurrence
      was suspected, and tumorectomy was performed. Pathological diagnosis was
      pleomorphic liposarcoma with cartilaginous metaplasia. A review of 6 cases of
      recurrent intrascrotal liposarcoma reported in Japan, including the present case,
      revealed that 5 cases recurred locally in the same lesion and were growing
      slowly. Therefore, we considered that intrascrotal liposarcoma should be resected
      as extensively as possible and observed for a long period.

PMID- 12229186
TI  - [A case of adrenal hematoma].
AB  - A right adrenal tumor was discovered incidentally in an ultrasonographic exam in
      a 45-year-old man. He was referred to our hospital for further examination and
      treatment of the adrenal tumor. The hormonal levels in his blood and urine were
      normal and hypertension was not observed. An ultrasonograph, computerized
      tomographic scan and magnetic resonance imaging showed a right adrenal tumor 7 cm
      in size. An adrenal hemangioma was most suspected, but a malignant tumor could
      not be excluded due to its size. Accordingly, a right adrenalectomy was
      performed. The histological diagnosis of adrenal hematoma was made. Adrenal
      hematoma is a rare disease in adults. It is very difficult to distinguish a large
      adrenal hematoma from a malignant tumor, the final diagnosis has to be made by
      histological study of the resected specimen.

PMID- 12229187
TI  - [A case of liposarcoma of the renal capsule].
AB  - A 58-year-old woman was referred to our institution for treatment of a left renal
      tumor revealed by follow-up computed tomography (CT) of a pancreatic tumor. The
      CT showed a heterogeneous, perirenal mass containing areas of fat density.
      Angiography showed no feeding artery. Left nephrectomy was performed and
      pathological examination revealed a well-differentiated liposarcoma of the renal
      capsule. At the third-month follow-up, the patient was completely asymptomatic
      and free of recurrence. Primary tumors of the renal capsule are uncommon and
      liposarcoma of the renal capsule is distinctly rare. There have been only 17
      reports of liposarcoma arising from the renal capsule in Japan. We, herein,
      report a case of liposarcoma of the renal capsule.

PMID- 12229189
TI  - [A case of lung collapse caused by endobronchial metastasis from renal cell
      carcinoma reinflated with laser and electrosurgical snaring].
AB  - A 62-year-old woman, who had undergone left nephrectomy for renal cell carcinoma
      and had received interferon-alpha for metastasis to the lung, was hospitalized
      because of cough, dyspnea and anorexia 16 months after nephrectomy. Chest
      radiography showed collapse of the right lung. We performed bronchoscopy and
      found a red polypoid tumor completely obstructing the right bronchus. Biopsy
      specimens showed clear cell carcinoma, similar to previous specimens of renal
      cell carcinoma. We removed the endobronchial tumor with laser and electrosurgical
      snaring, after which the right lung reinflated.

PMID- 12229188
TI  - [Two cases of renal cell carcinoma with ascites after interleukin-2 therapy].
AB  - One of the most common and problematic side effects of interleukin-2 therapy (IL
      2) is vascular leak syndrome (VLS). VLS is characterized by an increase in
      vascular permeability accompanied by extravasation of fluids and proteins from
      the capillary vessels into the tissues resulting in interstitial edema, weight
      gain, pleural effusion, ascites in severe form, multiple organ failure. We,
      herein, report two cases of VLS, which occurred following IL-2 therapy against
      metastatic renal cell carcinoma. One of them died of multiple organ failure one
      month after the cessation of IL-2 therapy.

PMID- 12229193
TI  - [The mechanism involved in recovery from bone fractures].

PMID- 12229190
TI  - Nephrogenic adenoma of the bladder: two case reports and literature review.
AB  - In the two cases we report here, tumors were diagnosed as nephrogenic adenoma by
      pathohistological examination. Case 1 was a 72-year-old female presenting with a
      bladder tumor 8 months after receiving ureteral tumor surgery. Transurethral
      resection of bladder tumor (TUR-Bt) was performed. Case 2 was a 57-year-old
      female who had received intravesical bacillus Calmette-Guerin (BCG) treatment 6
      times after her fifth TUR-Bt. Two tumors were found by cystoscopy, and TUR-Bt was
      performed. There have been 39 cases of nephrogenic adenoma of the bladder
      reported in Japan; 21 were male and 18 female with a mean age of 56.5 years. The
      main complaint was hematuria, which was seen in 16 cases followed by pollakisuria
      in 6 cases. Nephrogenic adenoma occurred after surgery of the urinary tract in 16
      cases, followed by urinary tract infection in 9 cases and intravesical BCG
      treatment in 6 cases. The ratio of cases occurring after intravesical BCG
      treatment has increased since BCG approval for bladder carcinoma treatment in
      December 1996 in Japan, and an increase in the number of cases is expected in the
      future.

PMID- 12229194
TI  - Sick sinus syndrome disclosed by the successful radiofrequency catheter ablation
      of persistent common atrial flutter.
AB  - Sick sinus syndrome was disclosed in a 77 year-old man after a radiofrequency
      (RF) linear catheter ablation of cavotricuspid isthmus for persistent common
      atrial flutter. Prolongation of corrected sinus node recovery time, sinoatrial
      conduction time and AH interval, as observed after RF ablation, suggested binodal
      (sinus as well as atrioventricular node) dysfunction. Adams-Stokes syndrome due
      to sinus arrest was encountered on the day of RF ablation and a permanent DDD
      pacemaker was implanted consequently. Our experience indicates that careful
      observation is very important after the RF ablation when atrial flutter is
      associated with sick sinus syndrome. The present case suggests that binodal
      dysfunction underlies persistent atrial flutter and vice versa.

PMID- 12229195
TI  - [Target pressure: can target be a nugget?].

PMID- 12229196
TI  - [Molecular pathology of retinitis pigmentosa].
AB  - BACKGROUND: Retinitis pigmentosa (RP) is primary, chronic, and hereditary
      chorioretinal degeneration characterized by photopsia, progressive visual loss
      with ring scotoma, and impairment of dark adaptation. Although modern molecular
      biology and molecular genetics have identified many causative genes, the
      molecular pathophysiology of RP is not fully understood, and no effective
      treatments have been found yet. In recent studies using animal models of RP, new
      treatments have been devised and their clinical use is being considered. METHOD:
      In terms of the molecular pathophysiology of RP, we summarized previous studies
      of genetic impairment of proteins involved in the phototransduction pathway and
      introduced new possible therapies for RP. RESULTS: We found that most
      abnormalities of the genes related with the photoxcitation and its inhibition
      process in the photoreceptor cells caused a variety of clinical manifestations of
      RP. CONCLUSION: So far, a variety of abnormalities of the genes causing RP have
      been identified. However, further studies of the relationship between the
      abnormalities and clinical expression are needed for better understanding of the
      pathophysiology of RP.

PMID- 12229197
TI  - [Ocular complications in systemic lupus erythematosus--choroidal and retinal
      pigment epithelial changes].
AB  - PURPOSE: Cotton wool patch and retinal hemorrhage are common ocular findings in
      systemic lupus erythematosus(SLE). Immunosuppressive treatment with
      corticosteroids may modify choroidal and retinal findings. We examined ocular
      complications, mainly choroidal and retinal pigment epithelium (RPE) changes in
      patients with SLE. MATERIALS AND METHODS: Fifty SLE cases[3 males, 47 females, 41
      +/- 15 (mean +/- standard deviation) year-old] were examined and treated in the
      departments of Internal Medicine and Ophthalmology of Osaka University Medical
      Hospital. RESULTS: Complications included cataract in 16 cases, glaucoma or
      ocular hypertension in 9 cases, and choroidal and retinal changes in 15 cases.
      Occlusive retinal vasculitis, retinal pigment epithelial dysfunction, such as
      pigment epithelial detachment, choroidal neovascularization and multiple
      posterior pigment epitheliopathy, in 6 cases, and branch retinal vein occlusion
      in 2 cases were detected as fundus complications. Average time period from the
      first detection of SLE was 13 years in patients with RPE changes. CONCLUSION:
      Long term corticosteroid therapy is probably responsible for the RPE
      complications.

PMID- 12229198
TI  - [Photopic negative response of eyes with normal-tension glaucoma].
AB  - PURPOSE: The purpose of this study was to investigate the behavior of the
      photopic negative response(PhNR) of cone-induced electroretinogram (cone ERG) in
      patients with normal-tension glaucoma (NTG). METHODS: Cone ERGs were recorded
      from 30 eyes of 30 patients with NTG according to the recording conditions of the
      International Society for Clinical Electrophysiology of Vision protocol which is
      now widely used in clinics. The amplitudes and implicit times of the PhNRs were
      measured and compared with normal controls. I further attempted to find a
      correlation between the PhNR amplitude loss and the cupping/disc ratio
      representing a loss of the nerve fiber layer and severity of visual field defbct.
      RESULTS: The PhNR amplitudes recorded from patients with NTG were significantly
      reduced compared with those from normal subjects (p < 0.05). However, the PhNR
      amplitude loss did not correlate with the cupping/disc ratio or the severity of
      visual field defect. CONCLUSIONS: The Results suggested that the PhNR amplitude
      qualitatively reflected ganglion cell loss in patients with NTG even under
      recording conditions which are widely used in the clinical field.

PMID- 12229199
TI  - [Target intraocular pressure and risk factors for progression of visual field
      loss in primary open-angle glaucoma].
AB  - PURPOSE: Evaluation of intraocular pressure(IOP) control below the target level
      stated by Iwata and study of risk factors for progression of visual field loss in
      primary open-angle glaucoma (POAG) despite successful reduction of IOP. SUBJECTS
      AND METHODS: Statistical difference of visual field deterioration between 27 eyes
      of POAG with IOPs above target levels and 48 eyes of POAG with IOP below target
      levels was examined for 28.1 +/- 10.2(mean +/- standard deviation) months. The
      relationship between the progression of visual field loss and factors of initial
      visual field loss, mean IOP, variance of IOP, peripapillary atrophy (zone beta),
      records of glaucoma surgery, age, and sex were studied in 48 patients(48 eyes)
      with IOPs below target levels. RESULTS: Eight of the 48 eyes(16.7%) showed
      progression of visual field loss with IOPs below their target levels whereas 15
      of the 27 eyes(55.6%) had IOPs above their target levels(p = 0.002). The risk
      factors for the progression of visual field loss in POAG despite good control of
      IOP were severity of initial visual field loss(p = 0.003), peripapillary
      atrophy(p = 0.002), and male sex(p = 0.03). CONCLUSIONS: The control of IOP below
      target level is beneficial for patients with POAG. However, the risk factors
      which represent circulatory damage, such as peripapillary atrophy, may have a bad
      influence on the continuing deterioration of visual fields in patients with
      severe visual field damage, independently of good control of IOP.

PMID- 12229200
TI  - [Elimination of apoptotic granulosa cells in atretic follicles: the role of
      macrophages and intact granulosa cells].
AB  - The present minireview describes a phenomenon by which phagocytic cells dispose
      of apoptotic granulosa cells during the process of atresia in mature (graafian)
      follicles from the guinea pig ovary. 1. Intact granulosa cells take part in the
      phagocytosis of dying granulosa cells at the early stages of atresia. 2. In
      addition, macrophages are present within large atretic follicles in order to
      remove dead granulosa cells and their debris. 3. These two kinds of phagocytic
      cells remain within the follicle until its atretic stages become considerably
      advanced. 4. A small number of macrophages are rarely discernible within the
      growing large follicles of the ovaries during the metestrus period. From these
      observations, the intrafollicular macrophages and the phagocytic granulosa cells
      are therefore considered to play an important role in the dynamics of the
      follicle, especially during both its development and atresia.

PMID- 12229201
TI  - [Plural absence of the lumbrical muscles observed in bilateral feet of a body].
AB  - A 69-year-old woman with lumbrical muscles missing in both feet was examined. The
      2nd and 3rd lumbrical muscles were absent in the right foot, while the 2nd, 3rd
      and 4th were missing in the left foot. Bilateral absence of lumbrical muscles is
      very rare, and present report is the third subsequent to two reported by Wood
      (1867, 1868). Moreover, this is the first report of bilateral and plural absence
      of lumbrical muscles. Results of this study and examination of the previous
      reports reveal that 1. the more laterally the lumbrical muscle is situated, the
      more often it is absent, and 2. plural absence of the lumbrical muscles occurs in
      neighboring two or three ones, i.e., the second and the third or the third and
      fourth in the case of the two muscles absence and the second, the third and the
      fourth in the case of the three.

PMID- 12229202
TI  - [Adjectives in international anatomical names and the corresponding words in
      Japanese anatomical names].
AB  - International anatomical names are expressed in Latin. In these names some
      adjectives denote anatomical names that consist of plural words, as deltoidea in
      Tuberositas deltoidea denotes Musculus deltoideus. We examined the words the
      correspond to such adjectives in Japanese anatomical names of the structures in
      the cranial and facial bones, and classified them into following groups: 1)
      adequate Japanese anatomical names, 2) original meanings of adjectives, 3) the
      word that is translated freely but lacks the letter corresponding a noun in Latin
      anatomical name, 4) Japanese anatomical names that correspond different Latin
      anatomical names, 5) Japanese anatomical names that correspond Latin anatomical
      names in the past.

PMID- 12229203
TI  - [MAP kinase cascade regulating synaptic vesicle localization in C. elegans as a
      model animal].

PMID- 12229204
TI  - [Function of MAPK signaling pathways in the immune system].

PMID- 12229205
TI  - [Stress-responsive MAP kinases].

PMID- 12229206
TI  - [Overview of the functions of MAP kinase in the nervous system].

PMID- 12229207
TI  - [Regulating mechanisms and functions of MAP kinases].

PMID- 12229208
TI  - [The molecular mechanisms of Alzheimer's disease: approach from the amyloid
      precursor protein].

PMID- 12229209
TI  - [Membrane permeable basic peptides: the potential of these peptides for the
      intracellular delivery of proteins and drugs].

PMID- 12229210
TI  - [Molecular bases for plant circadian clock and flowering: how does the quintet
      tell the time?].

PMID- 12229211
TI  - [XYZ of ABC proteins?: where is the goal for the study of ABC protein
      structure?].

PMID- 12229212
TI  - [Practical methods for management of chemical reagents].

PMID- 12229213
TI  - Total and subtotal aortic replacement for extensive aortic dissection in patients
      with or without Marfan's syndrome.
AB  - OBJECTIVES: Extensive aortic dissection with multiple entries often found in
      Marfan's syndrome patients ultimately requires replacement of the whole aorta. We
      present a surgical strategy and results for total and subtotal aortic
      replacement. METHODS: Subjects were 18 patients, including 14 Marfan's patients
      undergoing total (n = 13) or subtotal (excluding aortic arch) aortic replacement
      (n = 5), for DeBakey type I aortic dissection (n = 13) and DeBakey type IIIb
      aortic dissection with annuloaortic ectasia (n = 5) between February 1991 and
      April 2001. Mean age was 39.9 +/- 0.8 years--34.9 +/- 6.6 years in Marfan's
      patients vs. 57.7 +/- 4.7 years in non-Marfan patients. All operations were
      staged, with the mean number required per patient 3.1 +/- 0.8. RESULTS: Early
      mortality was 0% and late mortality 11% (2 of 18). Paraplegia or paraparesis
      occurring in 11%. Except for these patients, all current survivors enjoy good
      quality of life. CONCLUSIONS: Total and subtotal aortic replacement for extensive
      aortic dissection may decrease mortality due to rupture or associated disease.

PMID- 12229214
TI  - Bone marrow stromal cells contract synchronously with cardiomyocytes in a
      coculture system.
AB  - OBJECTIVES: Cell transplantation is a promising therapy for improving damaged
      heart function. Cardiac environmental factors are thought to be powerful
      differentiation inducers, but their effects are not well understood because of
      their in vivo nature. We simulated the cardiac environment using coculture and
      evaluated cardiomyogenic differentiation in bone marrow stromal cells and
      synchronous contraction with other cardiomyocytes. METHODS: Experiment 1. We
      evaluated the labeling efficiency, intensity, and pattern of green fluorescence
      in the transgenic mouse expressing green fluorescent protein-derived bone marrow
      stromal cells (GFP-BMCs) from initial plating through 8 weeks under fluorescent
      microscopy. Experiment 2. GFP-BMCs (10(5) cells) were cocultured with neonatal
      rat cardiomyocytes (10(5) cells). We also evaluated the incorporation, myogenic
      differentiation, and synchronous contraction of GFP-BMCs for 1 week under the
      same microscopy with a digital video camera. RESULTS: Experiment 1. All GFP-BMCs
      but red blood cells maintained green fluorescence from initial plating through 8
      weeks. Experiment 2. Some GFP-BMCs were incorporated in parallel with
      cardiomyocytes and showed myotube-like formation on day 1. On day 2, GFP-BMCs
      started to contract synchronously with cardiomyocytes. GFP-BMCs formed colonies
      and maintained synchronous contraction on day 7. CONCLUSIONS: Direct cell-to-cell
      interaction with cardiomyocytes is essential for myogenic differentiation and
      synchronous contraction of bone marrow cells. This coculture is a simple tool for
      simulating the cardiac environment and evaluating phenotypic changes in vitro.

PMID- 12229215
TI  - Evaluation of coronary artery bypass grafting in acute myocardial infarction.
AB  - OBJECTIVES: We evaluated coronary artery bypass grafting (CABG) in acute
      myocardial infarction (AMI) within 14 days of onset. METHODS: Of 1,450 patients
      undergoing isolated CABG in the last 12 years we retrospectively analyzed
      operative risk factors and studied the use of CABG in treating AMI in 66
      undergoing surgery during the AMI phase. We divided them into 2 groups: Group D
      (deceased: n = 8) and Group S (survivors: n = 58). RESULTS: Total operative
      mortality was 12.1% (8/66). Univariate analysis showed the following preoperative
      parameters to be significant in Group D: diabetes mellitus, cardiogenic shock,
      shortness of the interval between AMI onset and surgery, mean peak creatine
      phosphokinase-MB, AMI of the left main trunk, and failed recanalization of the
      infarcted artery. Multivariate analysis showed diabetes mellitus, cardiogenic
      shock, and AMI of the left main trunk as independent risk factors for hospital
      mortality. Intra-operative parameters between groups showed no statistical
      difference. Mortality in patients who did not suffer cardiogenic shock was zero.
      CONCLUSION: Maintenance of hemodynamics in the early phase is vital in treating
      AMI. The most important element in surgical intervention is revascularization of
      main branches. We concluded that CABG in AMI involves relatively low risk.

PMID- 12229216
TI  - Urgent off-pump coronary artery bypass grafting.
AB  - OBJECTIVES: The use of off-pump coronary artery bypass grafting (CABG) has become
      widespread, since it has proven less invasive and to promote early recovery. In
      this study, we investigated the efficacy of off-pump CABG in patients in the
      evolving phase of acute myocardial infarction. METHODS: Retrospective chart
      review was carried out for patients undergoing urgent isolated off-pump and on
      pump CABG at Shin-Tokyo Hospital Group between January 1991 and June 2001. The
      patients' demographic, operative data, and postoperative results were collected.
      RESULTS: The off-pump group consisted of 19 males and 11 females with a mean age
      of 72.0 years and the on-pump group of 91 males and 38 females with a mean age of
      64.3 years. Preoperative use of intraaortic balloon pumping and preoperative
      shock was more frequently observed in the on-pump group. The mean number of
      distal anastomoses was 3.1 +/- 0.9 in the off-pump group and 3.2 +/- 1.1 in the
      on-pump group (p = NS). Intubation time (18.5 vs 32.9 hours), ICU stay (3.4 vs
      4.9 days), and postoperative stay (13.5 vs 24.3 days) were significantly shorter
      in the off-pump group than in the on-pump group (P < 0.05). The frequency of the
      major complications was significantly lower in the off-pump group (9/30, 30%)
      than the on-pump group (65/129, 50.4%), especially for postoperative low output
      syndrome (p < 0.05). Multivariate analysis demonstrated a significant reduction
      in the recovery period by use of off-pump CABG. Early follow-up results were
      similar between the two groups, in terms of late cardiac events and survival.
      CONCLUSION: Urgent off-pump CABG is safe and provides early recovery, provided
      that the patient's intraoperative hemodynamics are taken into account.

PMID- 12229217
TI  - In situ pericardium repair of pulmonary venous obstruction after repair of total
      anomalous pulmonary venous connection.
AB  - A 13-month-old boy with recurrent pulmonary venous obstruction (PVO) after repair
      of total anomalous pulmonary venous connection (TAPVC, Darling IIa + Ia) was
      treated successfully with in situ pericardium repair consisting of unroofing
      coronary sinus at 2 months. At 8 months, stenosis of the right upper and lower
      pulmonary veins (PV) and left lower PV were detected, and PVO was relieved via
      resection of the stenosis site and recutback. Echocardiography 3 months later
      showed obstructed bilateral PVs and connection between left PVs and vertical
      veins. At reoperation, we conducted in situ pericardium repair for right PVO and
      anastomosed left PVs to the left atrial appendage. The postoperative course was
      satisfactory. Echocardiography 12 months later showed no evidence of PVO, but
      cardiac catheterization 12 months later showed mild obstruction on the right side
      and normal venous drainage on the left. Although the long-term prognosis is
      unknown, this sutureless technique is effective in recurrent PVO.

PMID- 12229218
TI  - Reoperation for a Starr-Edwards aortic valve implanted 28 years earlier.
AB  - A 56-year-old man admitted with dyspnea had undergone aortic valve replacement
      using a Starr-Edwards ball valve to treat aortic regurgitation 28 years earlier.
      Chest radiography showed moderate cardiomegaly, moderate pulmonary edema, and
      mild pleural effusion. Echocardiographic examination showed severe mitral
      regurgitation. The mitral valve was replaced using a St. Jude Medical prosthesis,
      and the Starr-Edwards aortic valve was replaced using a CarboMedics prosthetic
      valve. The cloth covering on the Starr-Edwards valve had worn away and pannus had
      formed. The patient's postoperative course was uneventful, and he was discharged
      on postoperative day 35.

PMID- 12229219
TI  - Solitary skin metastasis after lung cancer resection.
AB  - A 75-year-old woman admitted for an abnormal chest X-ray shadow was found in
      transbronchial lung biopsy to have malignant cells. After right lower lobectomy
      with mediastinal lymph node dissection, pathological examination showed primary
      pulmonary squamous cell carcinoma (pT2N1M0, stage IIB). After discharge, we
      followed her up as an outpatient, with oral administration of uracil and futrafur
      (300 mg/day). Five months postoperatively, a subcutaneous mass detected on her
      back and surgically removed was found histologically to be metastatic squamous
      cell carcinoma of subcutaneous tissue from lung cancer. No other metastases were
      found. The patient has survived 3 years and 3 months since primary surgery and
      remained cancer-free 2 years and 11 months since resection for skin metastasis.
      Given that skin metastasis is detected when most patients are in an advanced
      stage of disease, our case was a rare one of solitary skin metastasis after
      resection for lung cancer.

PMID- 12229220
TI  - Swan-Ganz catheter-induced pseudoaneurysm of the pulmonary artery.
AB  - Pseudoaneurysm of the pulmonary artery (PA) induced by Swan-Ganz catheter injury
      is an important complication with high mortality. We report a case of PA
      pseudoaneurysm treated by PA repair. A 52-year-old woman developing infiltrate in
      the right lung field in chest radiography after a second mitral valve replacement
      was diagnosed with PA pseudoaneurysm confirmed by contrast-enhanced computed
      tomography and pulmonary angiography. The cause was considered Swan-Ganz catheter
      injury. The patient was carefully observed because there was no evidence of
      bronchial hemorrhage. The perforation was closed and the cavity plicated under
      extracorporeal circulation to avoid delayed rupture of the pseudoaneurysm when
      she underwent a third mitral valve replacement.

PMID- 12229221
TI  - Massive right pleural effusion and ascites caused by a primary constrictive
      pericardial band.
AB  - A previously healthy 57-year-old woman with peripheral edema and exertional
      dyspnea had diminished right breath sounds and edema of both legs. Chest
      radiography showed massive right pleural effusion, and abdominal computed
      tomography showed ascites. During cardiac catheterization, pressure curves of
      both ventricles showed "dip-and-plateau" patterns. We diagnosed constrictive
      pericarditis and conducted pericardiectomy. During surgery, we found a thick
      fibrous pericardium surrounding the entire heart and a band of calcium in the
      atrioventricular groove. Histological examination of excised pericardial tissue
      showed fibrosis, hyalinization, and calcification, with thickening of < or = 18
      mm. Cases of localized pericardial thickening, including constricting bands in
      the atrioventricular groove, are rare and many such complications occur
      postoperatively. We report a rare case of primary constrictive pericardial band
      resulting in massive right pleural effusion and ascites.

PMID- 12229222
TI  - Angiocentric immunoproliferative lesion of the lung.
AB  - Angiocentric immunoproliferative lesion (AIL) is the angiocentric and
      angiodestructive process of lymphoreticular cells with vascular invasion. AIL of
      the lung is rare. We treated a 57-year-old woman with AIL of the lung in whom
      chest radiography and computed tomography showed ground-glass opacity in the left
      lower lobe and lingular segment. Since macroscopical and intraoperative lung
      biopsy findings could not rule out the possibility of malignancy, including
      malignant lymphoma, we conducted left pneumonectomy. Immunohistological
      examination of the tumor showed that infiltrating lymphocytes consistent with
      AIL. Because tumor markers such as serum LDH and soluble IL-2 receptor increased
      postoperatively, we conducted systemic chemotherapy, after which elevated serum
      tumor markers decreased.

PMID- 12229223
TI  - Benefits of further implementing video-assisted thoracic surgery.

PMID- 12229224
TI  - [Stressor and stress reduction strategies for computer software engineers].
AB  - First, in this article we discuss 10 significant occupational stressors for
      computer software engineers, based on the review of the scientific literature on
      their stress and mental health. The stressors include 1) quantitative work
      overload, 2) time pressure, 3) qualitative work load, 4) speed and diffusion of
      technological innovation, and technological divergence, 5) low discretional
      power, 6) underdeveloped career pattern, 7) low earnings/reward from jobs, 8)
      difficulties in managing a project team for software development and establishing
      support system, 9) difficulties in customer relations, and 10) personality
      characteristics. In addition, we delineate their working and organizational
      conditions that cause such occupational stressors in order to find strategies to
      reduce those stressors in their workplaces. Finally, we suggest three stressor
      and stress reduction strategies for software engineers.

PMID- 12229225
TI  - [Stress management in large-scale establishments].
AB  - Due to a recent dramatic change in industrial structures in Japan, the role of
      large-scale enterprises is changing. Mass production used to be the major income
      sources of companies, but nowadays it has changed to high value-added products,
      including, software development. As a consequence of highly competitive inter
      corporate development, there are various sources of job stress which induce
      health problems in employees, especially those concerned with development or
      management. To simply to obey the law or offer medical care are not enough to
      achieve management of these problems. Occupational health staff need to act
      according to the disease type and provide care with support from the Supervisor
      and Personnel Division. And for the training, development and consultation
      system, occupational health staff must work with the Personnel Division and
      Safety Division, and be approved by management supervisors.

PMID- 12229226
TI  - [Relationship between the augmentation index of central artery pressure and
      health examination data].
AB  - Arteriosclerosis is one of the major determinant of cardiovascular risks. The
      augmentation index (AGI) is a measure of systemic arterial stiffness derived from
      the ascending aortic pressure waveform. We examined the relationship between the
      AGI of the aorta measured by SphygmoCor (A + CorMedical Ltd. Australia) and the
      data from the health examination of 125 males and 31 females working for a steel
      company. In females the AGI was significantly higher than that in males. As the
      subjects were males and females significantly different in age, smoking habit,
      blood pressure, and other conditions, these data were analyzed separately for
      males and females. In males, smokers had a high AGI. Employees with hypertension
      had a significantly higher AGI than employees with normotension. The employees
      with hypertensive retinopathy had a higher AGI. The studies indicated that AGI
      was associated with age and diastolic blood pressure in both males and females.
      The items of age, volume of alcohol consumption per day and the health
      examination results such as BMI, total cholesterol, triglyceride, HDL
      cholesterol, fasting plasma glucose, and the body fat ratio of employees in the
      high AGI group (AGI:24% or more) n = 39 and low AGI group (AGI:23% or less) n =
      86 were compared. The results suggested that employees with high AGI were older
      and had higher diastolic blood pressure than employees with low AGI. In the high
      AGI group, the percentage of employees with hypertension was significantly higher
      than that in the low AGI group. These results of stepwise regression analysis
      indicated that age, smoking habit and diastolic blood pressure were significant
      and independent predictive factors for arteriosclerosis. AGI of the central
      artery is considered to be a useful parameter for assessing arteriosclerosis and
      for guiding health promotion.

PMID- 12229227
TI  - Meeting the challenges of a changing profession.

PMID- 12229228
TI  - Birmingham Eye Trauma Terminology (BETT): terminology and classification of
      mechanical eye injuries.
AB  - Lacking a standardized terminology of eye injury types, it is impossible to
      fulfill a very basic requirement in medicine: that all communications be
      unambiguous. Accurate interpretation of published research results, which plays
      an absolutely crucial role in determining how an individual patient with an eye
      injury is treated, becomes difficult. This article presents an internationally
      standardized system that finally allows accurate description of eye injuries of
      all types.

PMID- 12229229
TI  - Epidemiology and socioeconomics.
AB  - Ophthalmologists should be responsible for a systemic collection of standardized
      data on the occurrence of eye injuries. Such a database is the key for designing
      prophylactic measures to successfully prevent ocular trauma. The USEIR model,
      whether reporting takes place over the Internet [www.USEIRonline.org
      www.WEIRonline.org (worldwide)] or on paper, has proved to be an efficient
      epidemiological tool. Use of this model in different countries has allowed making
      unbiased comparisons between regions or countries, highlighting injury patterns
      that may be different in different geographical areas, and pinpointing areas
      where prophylaxis (through legislation and public campaigns) appears most
      effective. Participation of all ophthalmologists who evaluate/treat patients with
      serious eye trauma is strongly encouraged.

PMID- 12229230
TI  - Evaluation of patients with ocular trauma.
AB  - When confronted with the ocular trauma patient, the initial evaluation always
      begins with the assessment of the patient. Once it has been determined that the
      patient is stable, and other serious nonocular injuries have been addressed, a
      thorough medical/surgical history is taken followed by a more focused ocular
      history. Key elements include prior surgery, trauma, and any previously existing
      eye disease. A full examination is carried out in a methodical and rational
      fashion, beginning with gross external inspection. Visual acuity is measured in
      each eye independently. Optic nerve function is assessed by testing for a
      relative afferent pupillary defect, performing gross confrontational visual field
      testing, identifying any relative difference in subjective brightness perception,
      and checking color vision. If appropriate, the IOP is measured and a careful slit
      lamp examination is performed, combined with dilated indirect ophthalmoscopy.
      Obvious open globe injury can often be appreciated with a simple penlight
      examination. Uncooperative patients should be examined under anesthesia in a
      controlled, monitored setting involving experienced critical care personnel.
      Additional information may be obtained utilizing ancillary testing (primarily CT
      and ultrasonography). If the combination of clinical findings and ancillary
      testing is still not definitive, then formal exploration under anesthesia in the
      operating room in recommended. Photodocumentation is recommended whenever
      feasible. Figs. 1-14 provide an overview of many of the points stressed above.

PMID- 12229231
TI  - The Ocular Trauma Score (OTS).
AB  - Only based on a standardized terminology of ocular trauma terms, and using a very
      large number of injuries treated by a wide variety of ophthalmologists, could a
      reliable method be developed so that the functional outcome of a serious eye
      injury can be predicted with reasonable certainty. The authors used the databases
      of the United States and Hungarian Eye Injury Registries and, with a grant from
      the National Center for Injury Prevention at the Centers for Disease Control and
      Prevention, designed such a system.

PMID- 12229232
TI  - Counseling and rehabilitation.
AB  - Counseling is an art learned over a lifetime, from other physicians during formal
      training and from one's personal counseling experiences. The effort to develop
      this art will be greatly appreciated and richly awarded with personal
      satisfaction. The importance of counseling and rehabilitation for the ocular
      trauma victim is in treating the whole patient, not only the injured eye. Every
      effort should be made to help a patient achieve a positive attitude about his or
      her capabilities to successfully use residual vision and live a full and
      enjoyable life as a visually impaired person.

PMID- 12229233
TI  - Strategic thinking in eye trauma management.
AB  - Treating patients with serious eye injuries is not only a difficult, but also
      occasionally frustrating process. Mastering the details of the management of
      individual tissue lesions allows one to "see the tree" but does not provide
      vision of the entire forest. To develop a comprehensive understanding that leads
      to strategic thinking before making actual reconstruction efforts, the surgeon
      should follow a fairly rigorous thought process to find the best possible
      management option for the particular injury (Fig. 1). His or her suggestion, as
      well as detailed information on other options, should be discussed with the
      patient, and the decision regarding how to proceed is best if it meets the
      approval of, and is supported by, the patient. Such an approach has the highest
      chance of rewarding the patient and the treating physician.

PMID- 12229234
TI  - Adnexal trauma.
AB  - Injuries to the adnexa have both functional and cosmetic implications. This
      article details the conditions, and their treatment, which ophthalmologists
      should be familiar with.

PMID- 12229235
TI  - Corneal and scleral trauma.
AB  - Corneal and scleral wounds commonly occur in the context of serious eye trauma,
      and their management requires careful evaluation and planning prior to closure.
      The globe must be closed so that it is watertight with the original anatomy
      restored and the original function can be as closely approximated as possible.
      Closure of the cornea and sclera is different from the typical skin technique of
      "halving" the wound. Long corneal wounds are closed utilizing the Rowsey-Hays
      technique whereas scleral wounds extending posteriorly are closed in a stepwise
      fashion, proceeding posteriorly only after the anterior portion has been sutured.
      Suture removal from the cornea is dependent on a variety of factors including
      length of the laceration, age of the patient, and Keratorefractive anomalies
      caused by the sutures themselves.

PMID- 12229236
TI  - Anterior chamber abnormalities and cataract.
AB  - Material occurring in the anterior chamber as a result of trauma may be of little
      or major significance. The most common finding requiring treatment is hyphema.
      Close observation and (often surgical) treatment is especially important in
      patients at high risk: those with sickle cell disease, rebleeding, and elevated
      intraocular pressure. Cataract is a common complication in eyes sustaining
      serious trauma, although its presence may be difficult to confirm during the
      initial repair. The diagnosis is especially crucial because of the significantly
      increased risk of endophthalmitis. If the surgeon is able to determine that
      cataract is indeed present and hinders visualization of the posterior segment, or
      may lead to rapid elevation of the intraocular pressure, primary lens removal
      should be considered because vitreoretinal injuries are expected in approximately
      one-half of eyes, and an early retinal examination is mandatory in all eyes with
      lens trauma. Because one out of two eyes have posterior capsule injury,
      vitrectomy methods of lens removal are commonly required. Preservation of the
      posterior capsule is less important than avoiding traction on the anterior
      vitreous, because alternative methods of intraocular lens placement offer similar
      functional results.

PMID- 12229237
TI  - The uvea in ocular trauma.
AB  - The uveal tissue is frequently affected in ocular trauma. Its anatomic and
      physiologic changes are responsible for many of the early and late clinical
      manifestations seen in the traumatized eye. Together with the retina, the uvea
      may be the tissue most responsible for the final visual and functional outcomes
      of the eye. Understanding its pathophysiology is the first step leading to proper
      management and ultimately to vision preservation.

PMID- 12229238
TI  - Ocular trauma-related glaucoma.
AB  - Glaucoma following ocular injury is a multifactorial condition. Management of
      posttraumatic ocular hypertension is especially critical in that many of the
      complications that may develop are preventable. Management is aimed at preventing
      further damage to the injured eye.

PMID- 12229239
TI  - Vitreoretinal trauma.
AB  - During the last two decades, vitreous surgical techniques have become more
      refined, so it is now unusual that an eye cannot be saved, even following very
      severe ocular injury. This article reviews some of the more recent advances in
      the understanding and management of posterior segment complications of mechanical
      injury.

PMID- 12229240
TI  - Intraocular foreign bodies.
AB  - The most important rule in treating patients with an intraocular foreign body is
      that the primary goal of the intervention, while typically including foreign body
      removal, is comprehensive anatomical reconstruction of the injured eye so that
      the best possible visual outcome can be achieved. If the ophthalmologist is
      unable to perform such surgery, the patient should be referred to a facility
      where the expertise and personnel are available to address all treatable tissue
      lesions. If the foreign body is in the posterior segment, vitrectomy is usually
      necessary. With appropriate management, most eyes have a good chance of regaining
      and maintaining useful vision.

PMID- 12229241
TI  - Endophthalmitis.
AB  - The threat of posttraumatic endophthalmitis requires vigilance on the attending
      physician's part; it also raises several management issues that are still
      controversial. Table 2 provides an overview of the key points.

PMID- 12229242
TI  - Orbital trauma.
AB  - The orbit is designed to protect and nurture the eyeball. The seven bones of the
      orbit enclose a pear-shaped cavity. The bones of the superior and lateral orbit
      are extremely strong, as opposed to the bones of the inferior and medial orbit,
      which are extremely weak. The strengths and weaknesses inherent to the orbital
      bones produce a unique pressure safety valve, designed to protect the eyeball.

PMID- 12229243
TI  - [Structured patient education in oncology. A prospective study for implementing
      and effectiveness of interdisciplinary psycho-educational group intervention at a
      German university clinic].
AB  - AIM: To identify the target group for a structured educational group intervention
      in an acute cancer care setting, and to prove its effectiveness. PATIENTS AND
      METHODS: Cancer patients were given an opportunity to join an educational group
      intervention lasting 3 weeks (consisting of six times 1 hour). The intervention
      consisted of two major components: health education and coping skills.
      Participating patients (intervention group; n = 51) and nonparticipants (control
      group; n = 57) were evaluated at the beginning, then 2 months and 4 months later
      by means of standardized questionnaires (EORTC QLQ-C30, TSK, HADS, Henrich's
      FTP). RESULTS: Lower social and educational status, nonurban residency, males,
      and unfavorable prognoses together with palliative treatment intention were found
      less frequently (p < 0.05) in the intervention group. In comparison to the
      control group, the intervention group patients were characterized by a
      significantly greater desire for information and by more treatment-related fear.
      Improvements in disease-specific knowledge, certain quality of life elements, and
      in coping occurred only in the intervention group. Increases in the incidence of
      depression were found only in the control group. CONCLUSION: Patients with a more
      favorable prognosis, and a higher social and educational status, are more likely
      to get structured educational group intervention in an acute cancer care setting.
      For this subset of patients this intervention proves effective. Its importance
      for the standard care of cancer should be further investigated.

PMID- 12229244
TI  - [Value of malarone in therapy of malaria tropica].
AB  - BACKGROUND: A widespread resistance of falciparum malaria to common antimalaria
      drugs is observed during the last years. Long-distance travel to high-risk
      destinations of falciparum malaria will contribute to increased exposition of
      travelers to highly resistant parasites. PHARMACOLOGY: Malarone (GlaxoSmithKline)
      is a fixed combination of atovaquone and proguanil licensed for prophylaxis and
      treatment of falciparum malaria. Both atovaquone and proguanil demonstrate
      synergistic activity against liver and blood schizonts. Malarone is well
      tolerated with a low rate of side effects. Malarone has an excellent efficacy
      profile in nonimmune subjects. CONCLUSIONS: Malarone appears to be a valuable
      alternative malaria prophylaxis in case of intolerance of other antimalaria
      drugs. Atovaquone/proguanil is effective in treating acute uncomplicated malaria
      caused by multiresistant strains of Plasmodium falciparum.

PMID- 12229245
TI  - [Prognosis, staging and therapy of malignant pleural mesothelioma].
AB  - PROGNOSIS: Prognosis of pleural mesothelioma remains dismal. Regardless of the
      modality employed median survival ranges between 6 and 12 months, only 20% of
      patients survive 1 year. In 1996 the International Mesothelioma Interest Group
      (IMIG) published a widely accepted staging system. So far there is no effective
      standard therapy. Even very aggressive therapies do not basically influence the
      course of the disease. THERAPEUTICAL STUDIES: Despite numerous single-agent and
      combination chemotherapy trials no standard regimen could be found. Few agents
      yield reproducible response rates above 20%. The majority of the trials are
      inconclusive according to statistical criteria, as subject numbers are
      insufficient to prove or deny effectiveness. It also remains obscure in which
      stage of the disease patients may benefit from chemotherapy because of a lack of
      analysis of response rates within different stages. Striking is the lack of
      sufficient studies analyzing patients' quality of life treated with often very
      toxic regimens. DRUG TREATMENT: Systemic administration of interferons alone or
      in combination with chemotherapeutic agents did not result in higher response
      rates or prolonged median survival. In very early stages of the disease patients
      may have limited benefit from intracavitary, local administration of gamma
      interferon. MULTIMODALITY APPROACHES: Mere surgical procedures as extrapleural
      pneumonectomy or pleurectomy/decortication have been left in favor of
      multimodality approaches. Due to careful patient selection and improved operation
      techniques mortality could be reduced. Neither chemotherapy, radiotherapy nor
      photodynamic therapy can prevent local relapse which occurs in the majority of
      patients. RADIOTHERAPY: The effectiveness of primary radiation therapy remains
      controversial. Even very high doses of radiation cannot control tumor growth. It
      remains unclear whether radiation therapy may palliate tumor associated symptoms.
      Prophylactic radiation of puncture channels and thoracotomy scars is effective to
      prevent tumor growth caused by seeding of mesothelioma cells. PERSPECTIVES:
      Research of the biological behavior of mesothelioma resulted in first phase I
      gene therapy trials. The results of the few promising approaches tested in phase
      II and III trials with sufficient patient numbers have to be awaited until we
      have learned whether and in which stage of the disease patients may benefit from
      therapy.

PMID- 12229246
TI  - [Mediastinal ultrasound: technique and possible applications].
AB  - When a mediastinal disease is suspected, the conventional chest X-ray remains the
      diagnostic procedure of first choice. However, the gold standard for evaluation
      of the mediastinum is represented by thoracic computed tomography, which
      demonstrates all important structures of this region and supplies information
      about pathologic changes of the lung hilus and parenchyma. Until today, with the
      exception of echocardiography, noninvasive sonographic examination of the
      mediastinum is not routinely performed. The potential of this procedure, which is
      supported by the good accessibility to the region and its predominantly solid
      structure, appears not yet adequately used. To evaluate and compare the
      sonographic findings, it seems essential to establish a standardized examination
      procedure as well as a clear definition of anatomic regions. Since
      lymphadenopathy represents the most frequent pathologic finding in the
      mediastinum, the definition of the mediastinal regions is made with respect to
      the lymphatic pathways. Clinically relevant mediastinal lesions are predominantly
      located in the aortopulmonary window or the paratracheal region, which both
      permit facile access for sonographic examination. A transcutaneous diagnostic or
      therapeutic puncture of mediastinal lesions can safely be performed under
      sonographic guidance.

PMID- 12229247
TI  - [A rare case of cholestasis and macrohematuria in a 52-year-old patient].
AB  - CLINICAL SYMPTOMS: We report of a 52-year-old man from Egypt who suffered from 20
      kg weight loss within 6 months, jaundice, macrohematuria, and impaired renal
      function. INVESTIGATIONS AND THERAPY: Due to the ultrasound and the CT scan of
      the abdomen, a kidney tumor was suspected. A nephrectomy was planned but the
      biopsy of the kidney and liver intraoperatively revealed amyloid deposits. A
      plasma cell dyscrasia of 15% was found by bone marrow biopsy. Immunfixation
      showed an IgG-kappa light chain in plasma and urine. There was no osteolysis
      throughout the skeletal system. Thus, the patient had a plasmacytoma Stage II
      associated with IgG-kappa light chain AL-amyloidosis which was treated by
      chemotherapy (melphalan and prednisolone). CONCLUSION: This unusual case presents
      a cholestatic liver disease due to bile duct obstruction secondary to amyloid
      deposits. Although AL-amyloidosis is easily diagnosed by certain criteria, the
      disease is often recognized too late with consequently poor prognosis.

PMID- 12229248
TI  - [Hypo-osmolar hyponatremia as the chief symptom in hypothyroidism].
AB  - CASE HISTORY AND DIAGNOSIS: A 75-year-old male patient presented with a history
      of anorexia, muscle weakness, and increasing memory loss. He had mild pedal edema
      and decreased deep tendon reflexes. As the laboratory tests showed hypoosmolar
      hyponatremia and urinary sodium within the normal range, a syndrome of
      inappropriate ADH secretion (SIADH) was presumed. While neither the medical
      history nor any of the diagnostic procedures revealed any underlying pathology
      explaining the SIADH, laboratory tests showed significant hypothyroidism.
      Hypothyroid states are associated with significant changes in renal function, one
      of which is hypoosmolar hyponatremia. TREATMENT AND COURSE: Treatment included
      fluid restriction and hormone substitution and resulted in a quick correction of
      the hyponatremia and a clear improvement of the patient's cognitive function.
      CONCLUSION: It is concluded that the diagnosis of SIADH should only be made after
      thorough investigation of the adrenal and thyroid hormone status.

PMID- 12229250
TI  - [Herpes simplex virus encephalitis].

PMID- 12229249
TI  - [Spontaneous coronary spasm as a rare cause of survived sudden cardiac death].
AB  - CASE REPORT: A 39-year-old man was admitted to our intensive care unit after
      successful resuscitation because of ventricular fibrillation with clinical and
      electrographic signs of acute myocardial infarction. Coronary angiography showed
      normal coronary arteries. MINC syndrome (myocardial infarction with
      angiographically normal coronary arteries) was due to a severe proximal
      spontaneous spasm of the left anterior descending artery (LAD). Intracoronary
      ultrasound imaging demonstrated an eccentric fibrous plaque in the proximal
      segment of LAD and a fibrofatty plaque distal to the spastic segment. At the time
      of electrophysiologic study, the patient was noninducible. After starting therapy
      with calcium antagonist, nitrate and molsidomine, the patient was stable and
      symptom-free. CONCLUSION: Coronary spasm without significant organic stenosis is
      an important cause of sudden cardiac arrest and MINC syndrome. Because of the
      good prognosis under adequate treatment, exact diagnosis is important in the
      prevention of sudden death.

PMID- 12229251
TI  - [Coping with illness and the process of dying].
AB  - Coping with illness and the process of dying can be interpreted as an antinomy
      for a physician's work from ancient times. Successful coping is targeted by
      definition--at least implicitly--on preserving human life at the best quality
      possible. On the contrary, the process of dying leading to an individual's death
      remains out of scope. The aim of our study is to describe present concepts
      concerning the process of dying and successful coping with illness (i.e., with
      cancer) in order to look for the specific place of competent medical attendance
      and terminal care within this context.

PMID- 12229252
TI  - [Cost-effectiveness of quality improvement measures in health care].
AB  - GOAL: To discuss the costs and cost-effectiveness of quality improvement programs
      in health care. COST SAVINGS THROUGH QUALITY IMPROVEMENT: A quality improvement
      program saves costs if its investment costs are lower than savings from avoiding
      medical services. Cost savings are most likely realized if a) an overuse or
      misuse problem is targeted, b) many patients are affected, and c) striving for
      optimal quality is avoided. The overall prospect of cost savings is small,
      however. COST-EFFECTIVENESS OF QUALITY IMPROVEMENT PROGRAMS: From a societal
      perspective a quality improvement is economically attractive if an improvement in
      health status justifies its expenses including induced costs--even if total costs
      increase. In the USA a cost-effectiveness ratio of $50,000 per quality-adjusted
      life year is often applied as a maximum acceptable threshold value. From an
      institutional perspective the impact of a quality program on revenues is also
      important. An improvement of the image may increase the number of cases and thus
      revenues. For services reimbursed on a per-diem basis revenues behave according
      to changes in the length of stay. From an institutional perspective it is
      therefore reasonable to consider economic criteria when targeting problem areas.

PMID- 12229253
TI  - [108th Annual Meeting of the German Society of Internal Medicine].

PMID- 12229254
TI  - [Pharmacology of beta blockers and their significance for therapy of
      hypertension].
AB  - INTRODUCTION: Beta blockers are of great importance in the treatment of arterial
      hypertension, coronary heart disease, cardiac arrhythmias and heart failure.
      Their effects are mediated by the blockade of various alpha- und beta-receptors
      and specific com-pounds have been developed to address them. PHARMACOLOGY:
      Nonselective beta blockers (e.g. propranolol, nadolol, penbutolol, carvedilol)
      are to be separated from beta 1-selective blockers (e.g. metoprolol, atenolol,
      bisoprolol). Selectivity is never absolute and all beta blockers can cause
      problems in allergic asthma. Another important aspect is the intrinsic
      sympathomimetic activity of some compounds (e.g., pindolol, oxprenolol). CLINICAL
      APPLICATION: Together with diuretics, beta blockers are the oldest "modern"
      antihypertensive drugs. Only recently, interest has been raised because of their
      application in a hitherto forbidden indication, namely heart failure. In many
      patients, more than one indication applies to beta blockers, and differential
      therapy is able to cope with several conditions by one drug. Hypertension, atrial
      fibrillation and heart failure are often associated diseases as hypertension is a
      risk factor for both other diseases.

PMID- 12229255
TI  - [Beta blockers in post-infarction state].
AB  - In the 80s, randomized clinical studies and overviews have shown that adjunctive
      therapy with beta blockers can be beneficial post-myocardial infarction (MI).
      Despite this evidence, the use of beta blockers in the post-MI setting is far
      from uniform and now lags considerably behind the routine use of angiotensin
      converting enzyme inhibitors (ACEIs) in this clinical setting. Given the major
      advances in the management of myocardial infarction and its sequelae that have
      occurred in the last two decades (including the use of percutaneous transluminal
      coronary angioplasty [PTCA], thrombolysis, aspirin, ACEIs, and statins), there
      was clearly a need to revisit the issue of beta blocker therapy in patients with
      beta blockers in the setting of post-MI heart failure. For all these reasons, the
      CAPRICORN trial of carvedilol in post-MI left ventricular dysfunction was an
      important and eagerly awaited trial, which could show that carvedilol treatment
      post-MI on top of the so-called modern post-MI therapy reduces mortality. Further
      studies have to show whether this results can be repeated with other beta
      blockers.

PMID- 12229256
TI  - [Beta blockers in heart failure therapy with special reference to the COPERNICUS
      Study].
AB  - During the past 15 years, the pathophysiological concept of heart failure as a
      neurohormonal disease has influenced heart failure therapy substantially. ACE
      inhibitors have become the mainstay of heart failure therapy. In addition, beta
      blocker evolved to be effective in improving survival in this disease. Recently,
      the COPERNICUS study established the efficacy of carvedilol in severe heart
      failure and extended the benefits of this drug first observed in patients with
      mild and moderate symptoms to those with advanced disease. In this study,
      carvedilol resulted in a significant reduction of all-cause mortality and
      combined mortality and hospitalization, the frequency of hospitalizations, the
      risk of repeated hospitalizations, the number of days in hospital, the average
      duration of each admission and the utilization of treatments and procedures for
      heart failure. Carvedilol was well tolerated, improved the sense of well-being,
      was associated with a lower risk of a serious adverse event, particularly one
      related to the progression of heart failure and fewer patients requiring
      withdrawal of treatment for an adverse event. These favourable results were
      equally seen in all subgroups. Carvedilol treatment was even cost-effective in
      severe disease. Therefore, this new therapeutic option should be available to all
      patients with symptomatic systolic heart failure.

PMID- 12229257
TI  - [Urban & Vogel Robert Koch Award for carvedilol].

PMID- 12229258
TI  - [Hormonal hyperactivity in heart failure. Differences in beta blockers].
AB  - PATHOPHYSIOLOGY: Heart failure is characterized by a disturbed contractility and
      activation of neurohumoral mechanisms. Activation of the adrenergic system and
      the beta-adrenergic signal transduction pathway leads to downregulation of beta 1
      receptors of the heart muscle cell membrane. THERAPY: In addition to ACE
      inhibitors, diuretics and glycosides, beta blockers are an integral part in the
      combination therapy of patients with heart failure. Carvedilol, bisoprolol and
      metoprolol have been approved for use in patients with heart failure. Carvedilol
      is a nonselective beta-adrenoceptor antagonist with additional alpha 1-receptor
      blocking properties. Furthermore, it has additional antioxidative and
      antiproliferative effects. Bisoprolol and metoprolol are beta 1-selective beta
      blockers without intrinsic sympathomimetic activity. Based on the results of the
      US carvedilol trials, the CIBIS-II trial, the MERIT-HF study and the COPERNICUS
      study, it has been shown that beta blocker therapy can improve the prognosis of
      patients with compensated heart failure (NYHA II and III) and carvedilol can
      improve prognosis in severe heart failure (stage IV). Induction of therapy must
      be performed using very low doses, that can be increased in 2- to 3-week
      intervals. Drug dosages should be increased as much as possible. Besides a better
      prognosis, clinical symptoms and left ventricular ejection fraction can be
      expected to improve. The final effect can be expected only after months up to 1
      year. Therapy should continue lifelong. CONCLUSION: In summary, beta blocker
      therapy of congestive heart failure has been established as an integral part in
      the combination therapy of patients with all clinical stages of heart failure.

PMID- 12229259
TI  - Lecithin microemulsions in dimethyl ether and propane for the generation of
      pharmaceutical aerosols containing polar solutes.
AB  - Water soluble compounds have been incorporated into solution phase metered dose
      inhalers (MDIs) utilizing lecithin inverse microemulsions in dimethyl ether (DME)
      and propane. DME and propane acted as both solvent and propellant. Experiments
      utilizing model propellants (dimethylethyleneglycol (DMEG) and hexane) were used
      to investigate microemulsion physicochemical phenomena, and the results were used
      to design and interpret the technically more challenging MDI experiments. NMR and
      viscosity experiments with model propellants were consistent with a "sphere-to
      string" micellar shape change as the solvent was varied from pure DMEG to pure
      hexane. Water soluble solutes, including selected peptides and fluorescently
      labeled poly-alpha, beta-[N-(2-hydroxyethyl) D,L-aspartamide] (fPHEAs), dissolved
      in DME/propane dependent on lecithin and water content. MDIs containing
      microemulsions generated aerosols with mass median aerodynamic values ranging
      from 2.7 to 3.1 microns, within the range of commercially available formulations.
      Fine particle fraction values (50-70%) exceeded those of commercial formulations.
      fPHEA up to 18 kDa did not adversely affect the aerosol characteristics.
      Deposition of the aerosol onto a water surface resulted in the formation of
      liposomes with partially entrapped solute.

PMID- 12229260
TI  - Action of carriers on Carbamazepine dissolution.
AB  - It is well known that carriers can affect the dissolution of poorly soluble
      drugs. In this study, our aim was to investigate the dissolution enhancement of
      carbamazepine solid dispersed or mixed at different loading ratios in
      crospovidone, polyvinylpyrrolidone, and sodium starch glycolate. The physical
      state of the drug and the drug-polymer interactions in the solid state were
      investigated using differential scanning calorimetry (DSC) and x-ray diffraction
      analysis (XRD). Through the solubilization kinetics and dissolution rates
      studies, the in vitro drug availability of the systems was evaluated. An improved
      in vitro dissolution of the drug was obtained in all the binary systems that
      increased as the polymer content increased.

PMID- 12229261
TI  - Microparticle and liquid formulation of a novel HIV protease inhibitor.
AB  - The purpose of this study was to develop an improved dosage form of a novel
      protease inhibitor, LB71350. To overcome the dissolution rate-limiting step in
      oral absorption, amorphous LB71350 formulation was developed by spray drying
      ethanol solution of LB71350 and lecithin. Spray drying resulted in free flowing
      spherical microparticles with diameter < or = 5 microns. Powder X-ray diffraction
      confirmed that LB71350 in spray-dried microparticles and its aqueous dispersion
      was amorphous. In contrast to the aqueous suspension of crystalline LB71350,
      dispersion prepared from spray-dried microparticles showed significantly higher
      oral bioavailability in rat. Aqueous dispersion of spray-dried microparticles was
      more palatable than that of co-solvent solution formulation. Stability of
      dispersions depended on the concentration of dispersion and storage temperature.
      Dispersion containing 50 mg LB71350/mL was stable at 4 degrees C for 6 weeks
      without any significant physical or chemical changes. However, massive
      aggregation and crystallization of LB71350 occurred after 3 weeks at 25 degrees
      C. Dispersion containing 25 mg LB71350/mL showed sedimentation, which was re
      dispersible by gentle shaking. When dispersion stored for 4 weeks at 4 degrees C
      was given orally to rat, plasma concentration profiles were similar to those
      obtained after administration of fresh sample. On the basis of these results, the
      dispersion can be stored at least for 4 weeks at 4 degrees C. Spray-dried
      microparticles have been stable for 1 year at 4 degrees C without drug
      crystallization and further study is in progress to establish long-term storage
      stability. The present study establishes the feasibility of LB71350 liquid dosage
      formulation that is composed of free flowing spray-dried microparticles and
      aqueous vehicle to be reconstituted at the time of dispensing.

PMID- 12229262
TI  - Penetration enhancing effect of menthol on the percutaneous flux of nicardipine
      hydrochloride through excised rat epidermis from hydroxypropyl cellulose gels.
AB  - The aim of the present investigation is to study the penetration enhancing effect
      of menthol on the percutaneous flux of nicardipine hydrochloride through the
      excised rat epidermis from 2% w/w hydroxypropyl cellulose (HPC) gel system. The
      HPC gel formulations containing nicardipine hydrochloride and selected
      concentrations of menthol (0-12% w/w) were prepared, and evaluated for in vitro
      permeation of the drug through excised rat abdominal epidermis. The percutaneous
      flux of nicardipine hydrochloride across rat epidermis was enhanced markedly by
      the addition of menthol to the HPC gels. A maximum flux of nicardipine
      hydrochloride (227.70 +/- 1.30 micrograms cm-2 hr-1) was observed with an
      enhancement ratio of 7.12 when menthol was incorporated at a concentration of 8%
      w/w in a reservoir HPC system. The differential scanning calorimetry and Fourier
      transform-infrared spectroscopy data indicated that menthol increased the
      percutaneous flux of nicardipine hydrochloride through the rat skin by partial
      extraction of lipids in the stratum corneum. The results suggest that menthol may
      be useful for increasing the skin permeability of nicardipine hydrochloride from
      transdermal therapeutic system containing HPC gel as a reservoir.

PMID- 12229263
TI  - Spalling and sorption of tubing for peristaltic pumps.
AB  - Available tubing for peristaltic pumps tend to shed particulates into the
      solution due to their poor abrasion characteristics. Most commonly used flexible
      tubing is silicone rubber or polyvinyl chloride (Tygon) tubing. Two newly
      available tubing are manufactured from a composite of expanded
      polytetrafluoroethylene (Teflon PTFE) with platinum-cured silicone rubber (Sta
      Pure) and a tubing composite of PTFE with fluoroelastomer (Chem-Sure). These are
      claimed to resist spalling and deliver constant volume when used in peristaltic
      pumps. The four tubing were compared for spallation. They were also compared for
      sorption of methylparaben, propylparaben, and benzyl alcohol over a 72 hr study.
      Spallation studies indicate that Tygon and silicone tubing are prone to damage
      and shedding of particulates due to abrasion during use in peristaltic pumps
      while the Chem-Sure and Sta-Pure tubing are resistant to abrasion and spalling
      and show negligible shedding of particulates over 72 hr use in the peristaltic
      pump. Chem-Sure shows no spalling after 48 hr. Decrease in volume delivered is
      expected using Tygon and silicone tubing only. Chem-Sure tubing did not show any
      preservative losses. Tygon sorbed all preservatives tested to the greatest
      extent, followed by Silastic and Sta-Pure tubing, in decreasing order of
      sorption. Propylparaben was sorbed to the greatest extent. The tubing used appear
      to approach saturation in 24-48 hr. Chem-Sure and Sta-Pure tubing are ideal for
      use in peristaltic pumps or for general use for any demanding pharmaceutical
      applications.

PMID- 12229264
TI  - Formulation optimization and stability study of transdermal therapeutic system of
      nicorandil.
AB  - The aim of this research investigation was to fabricate acrylate-based stable
      transdermal therapeutic system (TTS) of nicorandil, which could deliver drug
      through transdermal route. Monolithic TTS was fabricated in pressure sensitive
      adhesives (PSAs)--(a) terpolymer (PSA1) of 2-ethylhexyl acrylate, methyl
      methacrylate, and acrylic acid, (b) copolymer (PSA2) of 2-ethylhexyl acrylate,
      methyl methacrylate, acrylic acid, and vinyl acetate, and (c) Eudragit E100
      pressure sensitive adhesive (PSA3). To enhance the flux of nicorandil, skin
      permeation enhancer N-methyl-2-pyrrolidone (NMP) was investigated at different
      concentrations (0.05-5%) in PSAs. Fabricated TTS was evaluated for in-vitro
      release and skin permeation through guinea pig skin. Maximum flux of nicorandil
      was observed from Eudragit E100 based TTS and kept for stability study at
      refrigeration, 25 degrees C/30% RH and 30 degrees C/60% RH. Patches were
      evaluated for various physicochemical parameters. Formulation was observed to be
      relatively more stable at refrigeration. Shelf life of the formulation was found
      to be 270, 270, and 30 days at refrigeration, 25 degrees C/30% RH and 30 degrees
      C/60% RH conditions, respectively. Nicorandil could be successfully derived from
      Eudragit E100 based TTS, but attention needs to be given to improve its chemical
      stability in formulation.

PMID- 12229265
TI  - An investigation of the mechanism of release of the amphoteric drug amoxycillin
      from poly(D,L-lactide-co-glycolide) matrices.
AB  - Amoxycillin-poly (D,L-lactide-co-glycolide) (PLGA) compacts were prepared by
      direct compression of both powder mixtures or films in a pre-heated press.
      Release profiles generally showed two phases separated by an induction period.
      Thus, both diffusion and polymer degradation mechanisms were involved in drug
      release, the relative importance of each depending on processing type and drug
      loading. Drug release parameters for each phase were determined. The fraction of
      total drug released, in the initial release phase, increased with drug loading
      and was much larger for compressed physical mixtures than for compressed
      composites prepared from co-evaporate films. Comparison of the polymer mass loss
      profiles of drug-loaded and drug-free discs indicated that the presence of the
      amphoteric drug amoxycillin had little impact on the polymer degradation rate, in
      contrast to the marked acceleration previously reported for basic drugs.
      Significant drug degradation occurred and was associated with release at later
      times. Release data was fitted to an equation accounting for degradation of the
      drug on release and suggested accelerated amoxycillin degradation during the
      polymer degradation controlled release phase, consistent with changes in pH in
      the microenvironment of the eroding compact.

PMID- 12229266
TI  - Multiple sources of sodium starch glycolate, NF: evaluation of functional
      equivalence and development of standard performance tests.
AB  - Sodium starch glycolate is a commonly used super-disintegrant employed to promote
      rapid disintegration and dissolution of IR solid dosage forms. It is manufactured
      by chemical modification of starch, i.e., carboxymethylation to enhance
      hydrophilicity and cross-linking to reduce solubility. It has been reported in
      the literature that the source of starch, particle size, amount of sodium
      chloride (reaction by-product), viscosity, degree of substitution and cross
      linking affect the functionality of sodium starch glycolate. Compendial assays
      provide an accurate representation of the chemical quality of an excipient, but
      they are not useful in describing the physical properties associated with the
      excipients. Physical characterization of sodium starch glycolate, NF revealed
      differences in particle size, surface area, porosity, surface morphology, and
      viscosity between two of the three sources examined. An automated liquid uptake
      test (in neutral and acidic medium) demonstrated similar initial rates of uptake,
      however, the extent of liquid uptake differed for the disintegrant powders
      examined. Settling volume was also observed to be different for the disintegrant
      from two sources. Lowering the pH of the medium reduced the rate and extent of
      liquid uptake and the settling volume in all instances. The extent of liquid
      uptake and settling volume was observed to be higher for the smaller sieve
      fractions in either medium, Although differences were also observed in the axial
      and radial disintegration force measurements of the pure disintegrant compacts,
      disintegration and dissolution of a model drug (hydrochlorothiazide) from either
      the soluble or insoluble core did not reveal any significant differences between
      the multiple sources.

PMID- 12229267
TI  - Evaluation of disintegration testing of different fast dissolving tablets using
      the texture analyzer.
AB  - The in vitro disintegration behavior of fast dissolving systems manufactured by
      the main commercialized technologies was studied using the texture analyzer (TA)
      instrument. Quantitative parameters were employed to characterize the effect of
      the major test variables on the disintegration profiles. The average
      disintegration profiles of the products were compared using the test conditions
      that minimized these effects and at the same time mimicked the in vivo situation
      in the patient's mouth. The differences in the disintegration mechanisms of the
      fast dissolving systems were reflected in the shape of their disintegration
      profiles and in the parameters derived from the profiles. The differences were
      explained in relation to the technology and/or formulation characteristics
      involved in the manufacture of each product. The in vitro disintegration times
      obtained under the simulated in vivo conditions were correlated with the reported
      in vivo disintegration times.

PMID- 12229268
TI  - Comparison of four artificial neural network software programs used to predict
      the in vitro dissolution of controlled-release tablets.
AB  - The purpose of this study was to evaluate four commercially available artificial
      neural network (ANN) software programs: NeuroShell2 v3.0, BrainMaker v3.7,
      CAD/Chem v5.0, and NeuralWorks Professional II/Plus for prediction of in vitro
      dissolution-time profiles of controlled-release tablets containing a model
      sympathomimetic drug. Seven independent formulation variables and three other
      tablet variables (moisture content of granules, granule particle size, and tablet
      hardness), for 22 tablet formulations, were used as the ANN model input. In vitro
      dissolution time-profiles at 10 different sampling times were used as the output.
      The models' optimum architectures were determined for each ANN software by
      varying the number of hidden layers and number of nodes in hidden layer(s). The
      ANN developed from the four software programs were validated by predicting the in
      vitro dissolution time-profiles of each of the 19 formulations, which were
      excluded from the training process. Although the same data set was used, the
      optimum ANN architectures generated from the four software programs were
      different. Using the four optimum ANN models, the plots of predicted vs. observed
      percentage of drug dissolved gave slopes ranging from 0.95 to 1.01 and r2 values
      ranging from 0.95 to 0.99 for all 190 dissolution data points for the 19 training
      formulations. The difference factors (f1) and similarity factors (f2) between the
      ANN predicted and the observed in vitro dissolution profiles were also used to
      compare the predictions for the four software programs. It was concluded that the
      four programs provided reasonable predictions of in vitro dissolution profiles
      for the data set employed in this study, with NeuralShell2 showing the best
      overall prediction.

PMID- 12229269
TI  - Thermal analysis and spectroscopic characterization of interactions between a
      naphthoquinone derivative with HP-beta-CD or PVP.
AB  - The purpose of the present study was to investigate the interaction between both
      hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and PVP-K30 with 2-hydroxy-N-(3
      methyl-5-ethyl-4-isoxazolyl)-1,4-naphthoquinone-4-imina (I), a synthetic
      derivative of isoxazolylnaphthoquinones that has demonstrated to exhibit
      important biological activity against S. aureus and T. cruzi. The continuous
      variation plot for I-HP-beta-CD system showed a 1:1 stoichiometry for the
      complex. Ultraviolet absorption spectroscopy indicates that the isoxazole moiety
      of I is preferably incorporated in the cavity. Furthermore, proton nuclear
      magnetic resonance spectroscopy suggests that this incorporation is made from the
      primary hydroxyl group side of the cyclodextrin. The validation of this
      incorporation is further evidenced by thermal analysis (DSC and TGA) and infrared
      spectroscopy. I-PVP-K30 interactions in solid state were demonstrated by
      combining the infrared spectroscopy data with the results of thermal analysis
      (DSC, TGA). These methods suggest that drug-polymer interaction probably occurs
      via intermolecular hydrogen bonding between the drug hydroxyl and polymer
      carbonyl groups.

PMID- 12229270
TI  - Oral cancer: history and establishing a diagnosis.

PMID- 12229271
TI  - Reducing morbidity and mortality from oral and oropharyngeal cancer.
AB  - There has been no reduction in the incidence of OOPCa, nor has the 5-year
      survival rate improved over the past 30 years. Most of these cancers are
      diagnosed in the later stages after they have grown to significant size, have
      become fixed to surrounding structures, hemorrhagic or painful or have caused
      noticeable impairment of speech or deglutition. To reduce the incidence of OOPCa
      and improve outcomes, the public must become more aware of the risk factors and
      seek regular oral cancer examination. More importantly, health professionals must
      incorporate a thorough oral soft tissue examination into their routine evaluation
      of all patients. Although an array of promising new technologies is becoming part
      of our diagnostic armamentarium, the most important factor is, as it has always
      been, an educated, astute and conscientious clinician.

PMID- 12229272
TI  - The Oral Cancer Consortium: a history.

PMID- 12229273
TI  - The mission: Jewish Healthcare International.

PMID- 12229274
TI  - If your case presentation is so good, why aren't you busier?

PMID- 12229275
TI  - An oral surgeon's view of the computer-assisted oral brush biopsy.

PMID- 12229276
TI  - [Toward integrated dengue control ].
AB  - Dengue is the most important arthropod-borne viral disease, it is characterized
      by mild symptoms to hemorrhagic manifestations and shock syndrome (DHF/DSS).
      Dengue and DHF/DSS have become major public health problems worldwide. In the
      urban areas of tropical and subtropical regions approximately 50 million
      infections occur annually. In Venezuela the situation is similar to the rest of
      the Americas. The impact of dengue points out the necessity of very organized and
      effective control programs. The emergency measures to combat the epidemics have
      had limited effects. There is not a specific management of dengue infections, no
      vaccine is commercially available and vector control is one of the alternatives
      to stop the spread of the disease, but an integral control program is needed,
      with each population's particularities and the state of epidemic risk in that it
      is. In the practice, it is to combine the environmental reparation with the
      changes in the human behavior taken place by the sanitary education and the
      necessary laws for it, integrated with the biological fight against the vector in
      the way and more appropriate moment and the chemical control in epidemic
      situations. This last aspect is fundamental as message of change toward an active
      attitude and of conscience, without which we can affirm with all security that
      doesn't exist government neither system of health able to solve this problem.

PMID- 12229277
TI  - [Oropharyngeal bacteria in asthmatic patients in the city of Maracaibo,
      Venezuela].
AB  - Bronchial asthma is an intercurrent disease that affects a major portion of the
      population. Neither its etiopathogenesis nor its complications have been fully
      established. The purpose of this study was to determine the composition of
      oropharyngeal bacterial flora in asthmatic patients and compare it with
      oropharyngeal bacterial flora in a group of healthy patients in order to
      establish its relationship with the pathogenesis of asthma and its complications.
      A sample consisting of 116 pharyngeal swabs was analysed from march 1995 to
      december 1996. 58 of the total amount of pharyngeal swabs corresponded to
      asthmatic patients (during asthmatic crisis), while the other 58 corresponded to
      healthy subjects. Common bacteriological culture techniques were carried out in
      order to obtain the bacteriological diagnosis. The results showed that isolation
      of transitory flora bacteria in asthmatic patients was 75.8%, which was
      significantly higher (p < 0.05) than in the control group (27.5%). Streptococcus
      pyogenes was the most frequent isolated bacteria in the group of asthmatic
      patients (17.2%), while Escherichia coli was the most frequent bacteria in the
      control group. No significant difference was found regarding sex and the presence
      of transitory flora bacteria. It was also found that enterobacteria and non
      fermenting negative gram bacillus increased with age in both groups; a higher
      incidence was observed in the group of 40-year-old subjects. These finding
      confirm the existence of a relationship between the asthmatic condition and the
      percentage of transitory bacterial flora carriers. The explanation to this
      phenomenon might be the frequent use of antibiotics and the possible
      contamination of the micro-nebulization equipment used for the treating the
      asthma crisis. This data must be considered when applying empiric therapy in
      asthmatic patients complicated with pneumonia. The possibility that certain
      infectious agents, including bacteria, could play a role in asthma pathogenesis
      is one of the questions that should be answered in future studies on this topic.

PMID- 12229278
TI  - [Human lymphocyte chromosome changes induced by x-rays].
AB  - With the aim of determine and characterize chromosomal alterations in human
      lymphocytes induced by x-rays, an experimental study was performed with auto
      control in four healthy donors (two males and two females). Peripheral blood was
      drawn, and divided in six aliquots: five of them were irradiated with 0.5, 1, 2,
      3 and 4 Gy using a linear accelerator and one aliquot was used as control for
      each donor. The chromosomal analysis was carried out with the "G banding
      technique". It was observed that as the irradiation doses were raised, the
      abnormal metaphases and frequency of chromosomal alterations increased as well.
      The majority of chromosomal alterations were of the structural type, of which the
      most relevant ones were translocations, fragile sites and deletions. A
      significant difference was observed between the exposed and non-exposed groups
      with regard to the irradiation doses and the apparition of chromosomal
      alterations (p < 0.05). Chromosome 1 was more frequently involved in structural
      chromosomal alterations, followed by chromosomes 3, 10, 6, 7 and 9. The results
      presented in this study indicate that chromosomal alterations induced by acute
      exposure to x-rays increase linearly once the irradiation doses are raised.
      Therefore, the cytogenetic analysis can be considered as a useful tool for the
      control of the absorbed radiation dose and its biologicals effects in men.

PMID- 12229279
TI  - [Enterobiasis among schoolchildren in a rural population from Estado Falcon,
      Venezuela, and its relation with socioeconomic level].
AB  - Between may and july 2001, a survey was conducted in order to investigate the
      prevalence and symptoms of Enterobius vermicularis infection and its relationship
      with the socio-economic status and household crowding of 154 schoolchildren aged
      6-12 years from a rural village in Falcon State, Venezuela. The Graham technique
      (perianal swabs with an adhesive cellulose tape) was used to perform the
      parasitological diagnosis. The overall prevalence was high (57.79%). There was no
      difference in the prevalence between sexes (X2 = 0.005; d.f. = 1) or ages (X2 =
      3.63; d.f. = 6) (p > 0.05), suggesting similar risk conditions for all
      individuals. Anal pruritus was the most common clinical finding (53.9%). Other
      less frequent manifestations were the following: perianal lesions (34.8%) and
      vulvovaginitis (32.6%). Graffar analysis revealed that the majority of
      schoolchildren belong to the poorer socioeconomic strata: IV (55.9%) and V
      (29.87%), with overcrowded living conditions. The correlation between E.
      vermicularis infection and crowding rates was found to be statistically
      significant (r = 0.98; p < 0.001). In the light on these results, it can be
      concluded that poverty, overcrowding, anal pruritus, scarcity of water,
      inadequate personal and community hygiene play a relevant role on the
      transmission dynamics and endemic maintenance of enterobiasis among
      schoolchildren from Sabaneta.

PMID- 12229280
TI  - [Mucormycosis. Report of 3 cases].
AB  - Mucormycosis is an acute and often fatal infection caused by a fungus of the
      Mucorales order of the Zygomycetes class. There are various clinical types,
      usually associated with an underlying disorder. The rhinocerebral mucormycosis is
      usually seen in diabetics, especially in ketoacidosis, but may also appear in
      healthy people. We report three cases of mucormycosis diagnosed since april 1987
      through january 2001 at the Dr. Domingo Luciani Hospital, Caracas, Venezuela. Two
      of them had diabetes and one was apparently healthy. The most common clinical
      presentation of mucormycosis was the rhinocerebral infection, seen in the two
      diabetic patients, both of them had cavernous sinus thrombosis one with
      involvement of the carotid artery. The other patient with sinus involvement had
      no predisposing factors. All patients were treated with amphotericin B and two of
      them had surgical debridement of involved tissue. We emphasize the importance of
      an early clinical diagnosis and treatment with surgical debridement of infected
      tissue combined with amphotericin B.

PMID- 12229281
TI  - [Basic aspects and measurement of the antioxidant vitamins A and E].
AB  - Vitamin E usually works as a biological antioxidant, preventing the oxidation of
      polyunsaturated fatty acids and proteins, for which it is considered an important
      protective factor in the development of diseases related to oxidative processes.
      Beyond its antioxidant properties, it has been involved also in genetic
      expression, mitochondrial metabolism, cell differentiation and immune system
      regulation. From the point of view of its antioxidant protection properties,
      values > or = 1200-1300 micrograms/dL are considered optimum levels (standardized
      according to plasmatic lipid levels). In relation to the beneficial advantage
      effects of vitamin E on primary or secondary atherosclerotic disease, data are
      not conclusive. Vitamin A is part of the organism's defense barrier against free
      radicals. Its antioxidant mechanism of action includes scavenging of single
      oxygen and thiol free radicals, and it also could be related to processes that
      involve genetic expression and cell differentiation. As an antioxidant, vitamin A
      plasmatic levels > or = 80 micrograms/dL are considered optimal. The highest risk
      of using this vitamin is related to its acute or chronic toxicity. Quantification
      of serum vitamin E (alpha tocopherol) and vitamin A (retinol) are made by high
      performance liquid chromatography (HPLC), method of high precision, sensitivity
      and reproducibility.

PMID- 12229283
TI  - PNA-mediated immobilization of supercoiled DNA.

PMID- 12229282
TI  - [Chronic complications of polycystic ovary syndrome. Review].
AB  - In addition to neuroendocrine abnormalities, women with polycystic ovary syndrome
      have insulin resistance and beta-cell dysfunction associated with a high
      frequency of metabolic syndrome components, such as glucose intolerance, type 2
      diabetes mellitus (DM-2), dyslipidemia and a higher risk for endothelial
      dysfunction, haemostatic abnormalities, hypertension and cardiovascular disease.
      Obesity, a common finding in this disorder, plays an important role in the
      development of metabolic and cardiovascular disorders. Early identification of
      patients and prompt initiation of insulin sensitizing therapy by pharmacological
      agents or changes in life style such diet and exercise might improve the
      metabolic and endocrine abnormalities and reduce the risk of DM-2 and
      cardiovascular disease in these patients.

PMID- 12229284
TI  - PNA openers and their applications.

PMID- 12229285
TI  - Colorimetric detection of PNA-DNA hybridization using cyanine dyes.

PMID- 12229286
TI  - PNA-mediated PCR clamping. Applications and methods.

PMID- 12229288
TI  - PNA fluorescent in situ hybridization for rapid microbiology and cytogenetic
      analysis.

PMID- 12229287
TI  - PNA clamping techniques for the determination of oncogene mutations.

PMID- 12229289
TI  - Detection of point mutations using PNA-containing electrophoresis matrices.

PMID- 12229290
TI  - Lipid-mediated introduction of peptide nucleic acids into cells.

PMID- 12229291
TI  - Synthesis of cell-penetrating peptide-PNA constructs.

PMID- 12229292
TI  - Antisense inhibition of bacterial gene expression and cell growth.

PMID- 12229293
TI  - In vitro transcription from peptide nucleic acid/DNA strand displacement loops.

PMID- 12229294
TI  - In vitro and in vivo studies on the pharmacokinetics and metabolism of PNA
      constructs in rodents.

PMID- 12229295
TI  - Solid phase synthesis of PNA oligomers.

PMID- 12229297
TI  - Synthesis of PNA-peptide conjugates.

PMID- 12229296
TI  - PNA technology.

PMID- 12229298
TI  - Parallel synthesis of PNA-peptide conjugate libraries.

PMID- 12229299
TI  - Thermodynamics of PNA interactions with DNA and RNA.

PMID- 12229300
TI  - Measurement of PNA binding to double-stranded DNA.

PMID- 12229301
TI  - Performance improvement.

PMID- 12229302
TI  - [Resuscitation].

PMID- 12229303
TI  - [New guidelines for resuscitation of adults].

PMID- 12229304
TI  - [Diagnosis and treatment in general practice of lower respiratory tract
      infections in adults].
AB  - Lower respiratory tract infections are common in the community. It might be
      difficult to differentiate between acute bronchitis, exacerbation of chronic
      obstructive pulmonary disease, and pneumonia. There is no satisfactory way of
      defining pneumonia by clinical criteria alone. Measurement of C-reactive protein
      is useful, but the specificity of the test is low, and must be carefully
      evaluated in comparison with the duration of illness and the clinical picture.
      The antibiotic management of lower respiratory tract infections must suppress
      Streptococcus pneumoniae. We therefore recommend that the first drug of choice
      should be penicillin V.

PMID- 12229305
TI  - [Increasing prevalence of specific IgE against aeroallergens in an adult Danish
      population--two cross-sectional studies in 1990 and 1998].
AB  - BACKGROUND: There is evidence that the prevalence of respiratory allergy has
      increased in children in many countries. However, this evidence is largely based
      on questionnaire data, and little is known about similar trends in adults. We
      investigated whether the prevalence of specific IgE to aeroallergens had
      increased in an adult general population over an 8-year period. MATERIAL AND
      METHODS: Two cross-sectional surveys were carried out in 1990 and 1998. A
      screening questionnaire on respiratory symptoms sent to random samples of 15-41
      year-old subjects living in Copenhagen (Denmark) preceded both surveys. Random
      samples of responders were invited to a health examination, which included
      assessment of specific IgE to six common aeroallergens. Totals of 312 (74.6% of
      those invited) and 482 (53.4% of those invited) subjects were examined in 1990
      and 1998, respectively. Serum samples from both surveys were analysed in 1999.
      RESULTS: The prevalence of specific IgE to at least one allergen increased
      significantly from 1990 to 1998 (26.5% versus 33.9%; odds ratio adjusted for sex,
      age, and season of examination, 1.63; 95% confidence interval, 1.15-2.32). This
      increase remained unexplained after adjustment for changes in questionnaire
      variables on life-style and home environment. The clinical significance of this
      increase was underlined by a corresponding increase in the prevalence of allergic
      rhinitis symptoms associated with specific IgE positivity. DISCUSSION: We found
      that the prevalence of specific IgE positivity to aeroallergens increased in an
      adult Danish general population from 1990 and 1998.

PMID- 12229306
TI  - [Lung function and respiratory tract disease among stonewool factory workers].
AB  - INTRODUCTION: We examined the respiratory health of a Danish workforce exposed to
      man-made vitreous fibres (MMVF) during production. MATERIAL AND METHODS: Workers
      with more than five years' occupational exposure to MMVF (n = 377) were compared
      to a group without MMVF exposure (n = 381). Respiratory health was assessed by
      questionnaire, dynamic spirometry, and measurement of transfer factor. The
      overall response rate was 63%. A sample of non-responders was assessed by
      questionnaire and spirometry. RESULTS: On most spirometric indices, the two
      groups had comparable values. However, a larger proportion (14.5%) of the exposed
      subjects had an obstructive flow pattern than the controls (5.3%). Subgroup
      analyses showed that the elevated risk of airway obstruction associated with
      exposure was confined to heavy smokers. Transfer factor and prevalences of
      symptoms and self-reported disease were similar in the two groups. DISCUSSION:
      There is no indication of excess risk of lung fibrosis. However, a number of
      exposed workers have some degree of airflow obstruction, which cannot be
      explained by known confounders. An additive or synergistic action between smoking
      and fibre exposure on airflow obstruction can be speculated.

PMID- 12229308
TI  - [Juvenile asymmetrical segmental spinal muscular atrophy].
AB  - We report the case of a man who had an insidious onset of asymmetrical distal
      muscle weakness of the upper extremity at the age of 17. Objective findings were
      1) muscular atrophy of calf and forearm flexor muscles and intrinsic hand
      muscles; 2) fasciculations; and 3) hand tremor. EMG and muscle biopsy showed
      neurogenic changes. MRI of the medulla and plasma creatine kinase were normal.
      Genetic testing for SMA-III was negative.

PMID- 12229307
TI  - [Does intake of gastric acid pump inhibitor affect the evaluation of the Lundh
      test?].
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of inhibition of
      gastric acid secretion on postprandial pancreatic secretion. MATERIAL OG METHODS:
      Fifteen healthy subjects and seven patients with chronic pancreatitis were
      entered in a randomised, double-blind, cross-over study of the exocrine
      pancreatic function after placebo or omeprazole 80 mg daily for three days. The
      exocrine pancreatic function was evaluated with the Lundh test. The pH was
      determined in the duodenum, and CCK and secretin were determined in plasma.
      RESULTS: As expected, a higher intraduodenal pH was found after inhibition of the
      gastric acid secretion, but no significant difference was seen in the
      concentration of pancreatic amylase in the duodenum. None of the subjects changed
      their diagnostic category during the test. Except for those with pancreatic
      insufficiency, in whom plasma secretin was lower after omeprazole, inhibition of
      gastric acid secretion had no effect on CCK or secretin in plasma. DISCUSSION:
      Inhibition of gastric acid secretion with high doses of omeprazole does not alter
      postprandial intraduodenal concentrations of alpha-amylase. It does not,
      therefore affect the evaluation of the Lundh test.

PMID- 12229309
TI  - [Future pharmacological treatment of inner ear disorders].

PMID- 12229310
TI  - [Is magnetic resonance cholangiopancreatography yet another alternative to
      endoscopic retrograde cholangiopancreatography?].

PMID- 12229311
TI  - [Treatment of pneumonia in younger patients with penicillin allergy].

PMID- 12229312
TI  - [Peanut allergy 1].

PMID- 12229313
TI  - [Peanut allergy 2].

PMID- 12229314
TI  - [Alcohol and patients with gout].

PMID- 12229315
TI  - [Don't bother about questionnaires!].

PMID- 12229316
TI  - [What is the "correct diagnosis of depression"?].

PMID- 12229317
TI  - [Folic acid fortification].

PMID- 12229319
TI  - Vaginal sterilisation as conception control.

PMID- 12229320
TI  - Experiments on tubal blocking for sterilisation without laparotomy.

PMID- 12229321
TI  - Contraceptives and other steroid drugs: their production from steroidal
      sapogenins.

PMID- 12229323
TI  - Let's think about abortion.

PMID- 12229348
TI  - Malaysia family-planning centers strive to maintain gains won in 15-year period.

PMID- 12229354
TI  - Comments on demography and population policy in the developing countries.

PMID- 12229365
TI  - [Etude statistique a propos de 496 utilisatrices).  (Monilial vulvovaginitis and
      oral contraceptives. Statistical study on 496 users)].

PMID- 12229368
TI  - The pill's blood clot risks disputed.

PMID- 12229372
TI  - Rupture of the uterus: 25 cases.

PMID- 12229379
TI  - Breast cancer risk profile used in detecting preclinical disease.

PMID- 12229384
TI  - Present status of oral contraceptives: 2. Complications, special considerations,
      relationship to cancer, cautions.

PMID- 12229402
TI  - Clinical activities in the region analyzed (Western hemisphere).

PMID- 12229414
TI  - (Reprint of) National Cancer Act Amendments of 1974. Conference Report.

PMID- 12229417
TI  - Colombia merges population affairs with ecology.

PMID- 12229420
TI  - Feast of famine: the choices for mankind.

PMID- 12229429
TI  - Population perspectives: some views from a sociologist.

PMID- 12229432
TI  - Bolivia firms up plans to launch nation's first family planning effort.

PMID- 12229440
TI  - Child spacing: as old as mankind.

PMID- 12229455
TI  - Immunologic control of reproduction in dogs.

PMID- 12229458
TI  - ["In vivo" efficiency of chemical spermicides studied by postcoital vaginal
      sampling].

PMID- 12229459
TI  - Confidence in contraception.

PMID- 12229472
TI  - Problems in the management of patients who have abortions.

PMID- 12229478
TI  - New drug helps women with "post-pill" problem.

PMID- 12229492
TI  - [Health and family planning. Reconsidering the evolution of ideas].

PMID- 12229496
TI  - Injectable medroxyprogesterone.

PMID- 12229508
TI  - Discovery learning: an ally in population education.

PMID- 12229501
TI  - More critics raise voices against estrogen therapy.

PMID- 12229511
TI  - What's better than the pill, vasectomy, celibacy and rhythm?

PMID- 12229543
TI  - Health services for mothers and children.

PMID- 12229528
TI  - Desirable and undesirable cutaneous effects of oral contraceptives.

PMID- 12229545
TI  - [Population projections for Japan, 1970-2050, estimated in February 1975].

PMID- 12229549
TI  - Trends in female sterilization in a teaching hospital.

PMID- 12229559
TI  - [Extramedical distribution of oral contraceptives.  Review of the literature].

PMID- 12229563
TI  - 1977 AID bill makes history;  noncontinuing resolution to start new fiscal year.

PMID- 12229565
TI  - New laws on population urged.

PMID- 12229573
TI  - The pill: is low estrogen the answer?

PMID- 12229574
TI  - MJH Clinic: Tilamsik team surpass 10,000 voluntary sterilizations.

PMID- 12229575
TI  - Family planners earn retirement bonus on plantations in India.

PMID- 12229579
TI  - Diagnostic X-rays are no cause for abortion - but caution is advised.

PMID- 12229583
TI  - [Effects of oral contraceptives on sexual behavior].

PMID- 12229590
TI  - Pharmacologic approaches to contraception in men.

PMID- 12229610
TI  - Women on the pill are opening up a small case of side effects every morning.

PMID- 12229612
TI  - Emphasizing the positive.

PMID- 12229613
TI  - The means of contraception:  the state of the art.

PMID- 12229635
TI  - Magdamayan: strategy for a rural family program (the fpop model).

PMID- 12229632
TI  - [Mechanical and chemical contraception in females].

PMID- 12229636
TI  - A free, informed and unpressured choice:  IPPF re-affirms policies on
      sterilization.

PMID- 12229653
TI  - The politics of contraception.

PMID- 12229654
TI  - [Family planning in the People's Republic of China].

PMID- 12229657
TI  - The role of models in planning.

PMID- 12229660
TI  - Coptic church program includes family planning.

PMID- 12229693
TI  - Application of the Brass-Sullivan method to historical data.

PMID- 12229694
TI  - A guide to the products of the 1970 census of population and housing.

PMID- 12229695
TI  - The world fertility survey.

PMID- 12229718
TI  - Programs for family planning in developing countries.

PMID- 12229720
TI  - Concept and role of eugenics:  implications for family planning in Asia.

PMID- 12229735
TI  - On method of assessment of overall impact of family planning programme on
      fertility.

PMID- 12229736
TI  - Population:  exploring the food-fertility link.

PMID- 12229738
TI  - [Fertility regulation activities of the Instituto Mexicano de Seguridad Social].

PMID- 12229739
TI  - [Pro-familia's baseline survey:  a study of fertility and contraception in a
      rural area of Colombia].

PMID- 12229741
TI  - Organisational problems of motivation in family planning.
AB  - Motivation -- a phenomenon of the human mind which is a product of purpose,
      desire, goal, perception, attitude and incentive, of emotions like anger, fear,
      or relationships of trust and suspicion, is an important organizational goal for
      implementing family planning.  It must therefore concern itself with strategies
      of improvement of the recipient of the services through participation and proper
      communication techniques.  After a need is generated, tension is created and a
      drive toward satisfaction begins.  The organization must provide the alternatives
      of choosing an action which will help satisfaction of the individual and
      organizational needs harmoniously.

PMID- 12229742
TI  - [Nutrition, health and population in strategies for rural development].

PMID- 12229743
TI  - [An analytical framework for the study of population and development
      interrelationships].

PMID- 12229751
TI  - After Caracas:  problems and perspectives.

PMID- 12229749
TI  - Two approaches. Institutional: leaving it all to the professionals.

PMID- 12229752
TI  - Man and the air.

PMID- 12229753
TI  - India:  ready or not, here they come.

PMID- 12229763
TI  - [Management and outcome of pregnancies associated with copper T Intrauterine
      contraceptive devices].

PMID- 12229766
TI  - World Population Plan of Action from the United Nations World Population
      Conference, Bucharest, August 19-30, 1974.

PMID- 12229764
TI  - [Conclusions and recommendations of the First International Hemispheric
      Conference on Adolescent fertility].

PMID- 12229771
TI  - Race and ethnic standards for Federal statistics and administrative reporting.

PMID- 12229773
TI  - [The menstrual cycle and sexual relations in users of the IUD and periodic
      abstinence].

PMID- 12229776
TI  - Why are astronomy and Frankenstein the faces of science? By Caveman.

PMID- 12229777
TI  - [Contribution of Japanese researchers to progress in the field of pulmonary
      medicine: Hypersensitivity pneumonitis].

PMID- 12229782
TI  - Expanding horizons in population control.

PMID- 12229783
TI  - Afghanistan's population: planning to avoid a crisis.

PMID- 12229784
TI  - Family planning goes to the people.

PMID- 12229818
TI  - Overcoming resistance to family planning.

PMID- 12229832
TI  - Family planning on Gandhigram pattern:  its application in Uttar Pradesh.

PMID- 12229833
TI  - Communication strategy for family planning.

PMID- 12229834
TI  - Family planning in People's Republic of China.

PMID- 12229835
TI  - Factors affecting fertility in a rural Indian environment.

PMID- 12229836
TI  - Kenya steps up population policy to reduce RNI.

PMID- 12229837
TI  - Welfare effects of international migration.

PMID- 12229848
TI  - [Medical ethic considerations on the use of IUDs as a method to prevent unwanted
      pregnancies].

PMID- 12229849
TI  - [Spontaneous and induced abortion.  An epidemiological study].

PMID- 12229850
TI  - [Breastfeeding: a forgotten art].

PMID- 12229851
TI  - Sudanese emigration to Saudi Arabia.

PMID- 12229852
TI  - A study on the relationships of lactation, postpartum amenorrhea and
      contraceptive practice.

PMID- 12229853
TI  - A study on use-effectiveness and extended use-effectiveness of contraceptive
      methods based on a program directed towards women having taken oral
      contraceptives in Seoul, Korea.

PMID- 12229854
TI  - The timing of births and birth intervals in relation to marriage, Taiwan, 1951
      1971.

PMID- 12229856
TI  - Conclusion without support - remarks on 'Efficacy and safely of doxyphyllin
      compared to Theophylline in chronic reversible asthma- a double-blind randomized
      placebo-controlled multicentre trial' by Goldstein MF, Chervinsky P (published in
      MedSciMonit, 2002; 8(4):CR297-304.

PMID- 12229855
TI  - [Migration patterns on the Chinese mainland after the mid-1980s].
AB  - "This paper studies the inter- and intra-provincial migration patterns, major
      streams, the demographic characteristics of migrants and their reasons based on
      the 1990 100% China census. Under the government efforts [to move] to a market
      economy, the household registration system gradually loses its function. The
      social and economic impacts of [the] significant size of floating population [in]
      cities are addressed." (SUMMARY IN ENG)

PMID- 12229857
TI  - Role of cellular adhesion molecules and growth factors in early atherogenesis.

PMID- 12229859
TI  - Codex task force agrees on final draft of principles for the evaluation of GM
      foods.

PMID- 12229858
TI  - PCR-based detection of Pythium and Lagendium DNA in frozen and ethanol-fixed
      animal tissues.

PMID- 12229860
TI  - The Buruli mysteries: unanswered questions surround a growing epidemic.

PMID- 12229861
TI  - Injection safety: misuse and overuse of injection worldwide.

PMID- 12229862
TI  - Attitudes of HIV-positive women toward zidovudine therapy during pregnancy.

PMID- 12229863
TI  - Drug metabolites in safety testing.
AB  - This report summarizes the deliberations of a multidisciplinary committee,
      sponsored by the Pharmaceutical Research and Manufacturers of America, on current
      "best practices" within the U.S. pharmaceutical industry in assessing the role of
      drug metabolites as potential mediators of the toxicity of new drug products.
      Input to the document was obtained from numerous sources, including members of
      the pharmaceutical industry, academic investigators, and representatives of
      regulatory agencies who attended a workshop on the subject in November 2000. The
      overall goal of the paper is to define practical and scientifically based
      approaches to the use of metabolite data that address contemporary issues in the
      safety evaluation of drug candidates. Although there remains a lack of consensus
      on how best to deal with several aspects of this complex subject, this paper
      raises a number of points to consider, which emphasize the need to treat drug
      metabolite issues on a case-by-case basis. It is hoped that the discussion will
      promote continued dialog among industrial scientists and regulators charged with
      ensuring the clinical safety of new therapeutic agents.

PMID- 12229864
TI  - Re: Zilbert AW, Farrell SA. External iliac artery laceration during tension free
      vaginal tape procedure.

PMID- 12229865
TI  - Brain stem blood flow, pupillary response, and outcome in patients with severe
      head injuries.

PMID- 12229866
TI  - Pattern of cerebral aneurysms in Morocco: review of the concept of their rarity
      in developing countries: report of 200 cases.

PMID- 12229867
TI  - The juxtaposition of a capillary telangiectasia, cavernous malformation, and
      developmental venous anomaly in the brainstem of a single patient: case report.

PMID- 12229868
TI  - Suprasellar meningiomas.

PMID- 12229869
TI  - Behavioral and morphological comparison of two nonhuman primate models of
      Huntington's disease.

PMID- 12229870
TI  - C1-C2 pedicle screw fixation with rigid cantilever beam construct: case report
      and technical note.

PMID- 12229871
TI  - Persistent iliac crest donor site pain: independent outcome assessment.

PMID- 12229872
TI  - Pharmacological therapy after acute cervical spinal cord injury.

PMID- 12229873
TI  - Steal affecting the central nervous system.

PMID- 12229874
TI  - [Who are you?].

PMID- 12229875
TI  - Questions raised by BRCA1/2-carrier screening programs.

PMID- 12229876
TI  - Progress of a Comprehensive Familial Cancer Genetic Counseling Program in the Era
      of BRCA1 and BRCA2.
AB  - BRCA1 and BRCA2 mutation carriers have an increased risk of developing breast
      and/or ovarian cancer. Technical advances in genetic testing have increased the
      need for genetic counseling services; therefore, we have developed a counseling
      program for these individuals. The purpose of this study is to characterize this
      population, assess level of interest in genetic testing, and evaluate our program
      over a 5-year period. Our Familial Cancer Genetic Counseling Program was
      established in November, 1994. Information was collected prospectively, with
      comprehensive evaluation including complete pedigree, risk assessment, and
      counseling by a genetic counselor, geneticist, and oncologist. Data were
      collected on risk level, and subsequent recommendations for screening and/or
      genetic testing. There were 824 contacts recorded from November, 1994, through
      August, 1999. To date, 162 families have undergone comprehensive genetic
      evaluation and counseling. 90 (56%) were seen for a concerning family history and
      72 (44%) were seen due to a personal history of malignancy. The majority of
      families had a significant level of risk with 126 (78%) families having two and
      70 (43%) families having three affected first-degree relatives. Of the 162
      families who received full counseling, 125 (77%) met criteria to recommend
      BRCA1/BRCA2 genetic testing. At this time, 30 of the 162 (18%) have had genetic
      testing. A brief phone contact or clinic visit is useful to screen individuals so
      that counseling can be directed toward truly high-risk families. In our program,
      the majority of families counseled were eligible for BRCA1/BRCA2 testing, but
      only 18% have elected to proceed at this time.

PMID- 12229877
TI  - Re: Vertebral hydatid cyst infection (Echinococcus granulosus): a case report.

PMID- 12229878
TI  - Vaccines: worth paying for the value returned.

PMID- 12229880
TI  - Adult onset and atypical presentation of  hemophagocytic lymphohistiocytosis in
      siblings carrying PRF1 mutations.

PMID- 12229881
TI  - Transcription of AML1/ETO in bone marrow and cord blood of individuals without
      acute myelogenous leukemia.

PMID- 12229882
TI  - Tumor necrosis factor alpha promoter polymorphisms and liver abnormalities of
      homozygotes for the 845G>A(C282Y) hereditary hemochromatosis mutation.

PMID- 12229883
TI  - Glycosylation of V region genes in follicular lymphoma as a result of the somatic
      hypermutation mechanism.

PMID- 12229884
TI  - TT virus does not contaminate first-generation recombinant factor VIII
      concentrate.

PMID- 12229885
TI  - Deep-vein thrombosis in patients with multiple myeloma receiving first-line
      thalidomide-dexamethasone therapy.

PMID- 12229886
TI  - Involvement of the MLL gene in T-lineage acute lymphoblastic leukemia.

PMID- 12229888
TI  - Managing HIV care: a global perspective.

PMID- 12229887
TI  - Megakaryocytes from chronic myeloproliferative disorders show enhanced nuclear
      bFGF expression.

PMID- 12229889
TI  - Policy watch. Attention, Mr. Thompson!

PMID- 12229890
TI  - AIDS vaccines, immunology, and what we have learned.

PMID- 12229891
TI  - Hyperlactatemia and lactic acidosis: should routine screening be considered?

PMID- 12229892
TI  - Adherence, resistance, and timing: current issues in the use of new therapies.
AB  - Nucleoside reverse transcriptase inhibitors (nucleoside analogues) are a central
      component of HAART regimens. Optimal adherence to and activity of the "nucleoside
      analogue backbone" is required to preserve the utility of the more cross
      resistant protease inhibitor and nonnucleoside analogue components of a highly
      active regimen, and a systematic approach to nucleoside analogue sequencing is
      needed to preserve the clinical activity of this class. As HIV treatment
      strategies move toward the long-term management of a chronic infection, treatment
      issues such as convenience, safety, and tolerability become even more important.
      Acute and chronic safety issues associated with individual drug classes are a
      growing concern. Because adherence is linked to convenience and tolerability, new
      agents with favorable safety profiles, low pill burdens, and little or no
      selection for drug resistance will be required to ensure long-term viral
      suppression.

PMID- 12229893
TI  - HIV-1-associated dementia: a basic science and clinical perspective.
AB  - HIV-1 associated dementia (HAD) is a metabolic encephalopathy induced by viral
      infection and fueled by immune activation of brain mononuclear phagocytes
      (perivascular and parenchymal macrophages and microglia). These same cells serve
      as reservoirs for persistent infection and sources for soluble neurotoxins.
      Neurologic impairments are manifested by cognitive, behavioral, and motor
      abnormalities that occur years after viral exposure and are associated with
      depletion of CD4+ T lymphocytes and high viral loads. Improvements in
      antiretroviral and adjunctive therapies have decreased HAD incidence, but
      cognitive dysfunction remains a cause of morbidity in many infected persons.

PMID- 12229894
TI  - Editorial comment: HIV-associated dementia--many questions remain.

PMID- 12229895
TI  - ASHP guidelines on preventing medication errors with antineoplastic agents.

PMID- 12229896
TI  - A clearer picture of HRT.

PMID- 12229897
TI  - What's the best way to treat an ingrown toenail, and how can I prevent this
      painful problem from recurring?

PMID- 12229898
TI  - What should you do when a piece of food "goes down the wrong tube"? Assuming that
      you can still breathe, do you want the food to go up or down?

PMID- 12229899
TI  - A statin in every medicine cabinet?

PMID- 12229900
TI  - Beta-blocker side effects: no big deal?

PMID- 12229901
TI  - Coming soon: trans fat labeling.

PMID- 12229902
TI  - Surgery for knee arthritis doesn't beat placebo.

PMID- 12229903
TI  - Do lo-carb diets deliver?

PMID- 12229904
TI  - Laparoscopic surgery for colon cancer.

PMID- 12229905
TI  - Improved prostate cancer treatment.

PMID- 12229906
TI  - Studies offer strategies for dust mite reduction.

PMID- 12229907
TI  - Simpler solutions for incontinence.

PMID- 12229909
TI  - From the Centers for Disease Control and Prevention. Community needs assessment
      of lower Manhattan residents following the World Trade Center attacks--Manhattan,
      New York City, 2001.

PMID- 12229908
TI  - [Current views on glaucoma, 1877].

PMID- 12229910
TI  - Angioplasty and stenting for stroke prevention: good questions that need answers.
AB  - Extracranial and intracranial angioplasty and stenting of the cerebral vessels
      are being performed more frequently. One clinical trial demonstrated equivalent
      outcomes between extracranial carotid angioplasty and carotid endarterectomy, but
      the results in both groups were suboptimal. Concerns remain about the iatrogenic
      stroke rate after angioplasty, especially for asymptomatic patients. Angioplasty,
      with or without stent placement, also offers a potential new therapeutic approach
      for patients with intracranial stenosis and vertebrobasilar lesions, although
      these procedures have been performed in uncontrolled fashion.

PMID- 12229911
TI  - Comparison of rizatriptan and other triptans on stringent measures of efficacy.

PMID- 12229912
TI  - The cerebellum may be directly involved in cognitive functions.

PMID- 12229913
TI  - Situation analysis of mortality in Bolivia.

PMID- 12229914
TI  - Case definition. Acute viral hepatitis.

PMID- 12229915
TI  - Case definition. Leprosy (Hansen's disease).

PMID- 12229916
TI  - The global youth tobacco survey: results in the Americas.

PMID- 12229917
TI  - E. coli kinetics--effect of temperature on the maintenance and respectively the
      decay phase.
AB  - The knowledge of enteric bacteria survival kinetic is very important for
      environmental scientists. Enteric bacteria and specifically the fecal indicator
      bacteria are typically used to measure the sanitary quality of water for
      recreational, industrial, agricultural and water supply purposes. They are
      released into the environment with feces, and are then exposed to a variety of
      environmental conditions that eventually cause their death. In general, it is
      believed that the fecal indicator cannot grow in natural environments, since they
      are adapted to live in the gastrointestinal tract. Studies have shown that fecal
      indicator bacteria survive from a few hours up to several days in surface water,
      but may survive for days or months in lake-sediments, where they may be protected
      from sunlight and predators. We assume that pathogens similar to the fecal
      indicator bacteria die at the same rate as fecal indicator bacteria. Therefore,
      if we find relatively high numbers of fecal indicator bacteria in an environment,
      we assume that there is an increased likelihood of pathogens being present as
      well. The kinetic of enteric bacteria survival in natural waters is affected by a
      large number of factors. One of them is the temperature. The aim of this
      contribution was the experimental research of the survival kinetic of enteric
      bacteria applying a simple mathematical formula, which describes the survival
      kinetic predicting the decay phase at various temperatures. We aspire that the
      results will lead both to the solution of many engineering problems and to future
      research.

PMID- 12229918
TI  - Evaluation of a fluorometric screening method for predicting total PAH
      concentrations in contaminated sediments.
AB  - A fluorometric screening method was used to estimate total polycyclic aromatic
      hydrocarbon (t-PAH) concentrations in sediments collected from the St. Louis
      River Area of Concern (AOC) in northeastern Minnesota. Sediments were collected
      as part of a Regional Environmental Monitoring and Assessment Program (R-EMAP)
      study to assess sediment quality in the AOC. The screening method was calibrated
      using a PAH surrogate standard consisting of eight PAHs commonly found in the St.
      Louis River system, at their approximate proportions. Estimated PAH
      concentrations were compared to GC/MS measured 'true' PAH concentrations to
      evaluate the overall predictive power of the screening method. Regression
      analysis of log transformed estimated versus true PAH concentration yielded an r2
      of 0.72 (n = 86). In addition, the rates of false positive and false negative
      predictions associated with the screening method were determined relative to
      different sediment effects concentrations (SECs) for total PAHs. In general, the
      rate of false positive predictions was shown to increase as the SEC criteria
      value decreased, while false negative rates remained consistently low (below 7%).
      Methodological recommendations which led to a three-fold reduction in false
      negatives, and the improved prediction of both high and low PAH samples, are
      presented.

PMID- 12229919
TI  - Causes of ambient toxicity in the Calleguas Creek watershed of southern
      California.
AB  - A combination of toxicity tests, chemical analyses, and Toxicity Identification
      Evaluations (TIEs) were used to investigate receiving water toxicity in the
      Calleguas Creek watershed of southern California. Studies were conducted from
      1995 through 1999 at various sites to investigate causes of temporal variability
      of toxicity throughout this system. Causes of receiving water toxicity varied by
      site and species tested. Investigations in the lower watershed (Revolon Slough,
      Santa Clara Drain, Beardsley Wash) indicated that toxicity of samples to the
      cladoceran Ceriodaphnia dubia was due to elevated concentrations of the
      organophosphate pesticide chlorpyrifos, while causes of intermittent toxicity to
      fathead minnows (Pimephales promelas) and the alga Selanastrum capricornutum were
      less clear. Investigations at sites in the middle and upper reaches of the
      watershed (Arroyo Simi and Conejo Creek) indicated that the pesticide diazinon
      was the probable cause of receiving water toxicity to Ceriodaphnia. Elevated
      ammonia was the cause of toxicity to fathead minnows in the upper watershed
      sites. Results of these and previous studies suggest that biota are impacted by
      degraded stream quality from a variety of point and non-point pollution sources
      in the Calleguas Creek watershed. Water quality resource manager's efforts to
      identify contaminant inputs and implement source control will be improved with
      the findings of this study.

PMID- 12229920
TI  - Phosphate run-off in the Nevezis River (Lithuania).
AB  - The long-term (40 yr) observation results of phosphates-phosphorus concentration
      and its runoff in the Lithuanian fourth largest river Nevezis are analysed.
      Amounts and peculiarities of background runoff, agricultural runoff, and point
      source pollution from towns were studied for various periods. It has been
      determined that phosphates enter into the river Nevezis mainly from towns
      (76.5%), from agriculture only up to 16%, and the background runoff for 7.5%.
      Considerable agricultural influence was observed in 1979-1991, when the phosphate
      runoff increased to 22 kg P km(-2) a(-1) and formed in 1984 33% of the entire
      runoff. A relation of the phosphates runoff from agriculture, for the entire
      study period, was obtained with the number of animals in the river's basin. Since
      1990, when the number of animals started to decrease, the runoff of phosphates
      decreased too. Now the phosphates runoff from agriculture formed only 2% of the
      entire runoff. Water in the river Nevezis is heavily polluted with phosphate,
      according to the EU general classification of the water quality of rivers,
      although the Lithuanian pollution norms for effluents discharging to surface
      water are not exceeded. Norms for effluents discharging in the rivers from point
      sources pollution should be made stricter and the highest permitted ratio between
      the phosphorus load in the river and its water discharge should be established.

PMID- 12229921
TI  - Methods development and use of macroinvertebrates as indicators of ecological
      conditions for streams in the Mid-Atlantic Highlands Region.
AB  - The Mid-Atlantic Highlands Assessment (MAHA) included the sampling of
      macroinvertebrates from 424 wadeable stream sites to determine status and trends,
      biological conditions, and water quality in first through third order streams in
      the Mid-Atlantic Highlands Region (MAHR) of the United States in 1993-1995. We
      identified reference and impaired sites using water chemistry and habitat
      criteria and evaluated a set of candidate macroinvertebrate metrics using a
      stepwise process. This process examined several metric characteristics, including
      ability of metrics to discriminate reference and impaired sites, relative scope
      of impairment, correlations with chemical and habitat indicators of stream
      disturbance, redundancy with other metrics, and within-year variability. Metrics
      that performed well were compared with metrics currently being used by three
      states in the region: Pennsylvania, Virginia, and West Virginia. Some of the
      metrics used by these states did not perform well when evaluated using regional
      data, while other metrics used by all three states in some form, specifically
      number of taxa, number of EPT taxa, and Hilsenhoff Biotic Index, performed well
      overall. Reasons for discrepancies between state and regional evaluations of
      metrics are explored. We also provide a set of metrics that, when used in
      combination, may provide a useful assessment of stream conditions in the MAHR.

PMID- 12229922
TI  - Bioterrorism and civil liberties.

PMID- 12229923
TI  - Bioterrorism and civil liberties.

PMID- 12229924
TI  - Stem cells and neurological disorders.

PMID- 12229925
TI  - Cancer epigenetics and methylation.

PMID- 12229926
TI  - Taxonomic bias and vulnerable species.

PMID- 12229927
TI  - Consequences of Siberian Traps volcanism.

PMID- 12229928
TI  - The physician as storyteller.

PMID- 12229929
TI  - Growing physician access problems complicate Medicare payment debate.
AB  - Projected cuts in Medicare physician payments raise serious concerns that
      Medicare beneficiaries will lose access to needed physician services. A study by
      the Center for Studying Health System Change (HSC) shows growing physician access
      problems among Medicare and privately insured patients. Patients have the most
      difficulties obtaining care from specialists and in certain communities.
      Proposals to increase Medicare fees across the board may prevent deterioration of
      access for Medicare beneficiaries but are unlikely to address system-wide access
      problems that vary by specialty and market.

PMID- 12229930
TI  - In situ immunocytochemical detection of potyviral proteins in plant cells.
AB  - A method for in situ protein immunodetection using a peroxidase labeling system
      is described for detecting functional and structural proteins encoded by potato
      virus Y (Tunisian isolate) in plant tissues. Such Potyviruses are characterized
      by the accumulation of inclusion bodies containing viral encoded proteins other
      than coat protein. These proteins are functional at early stages of infection,
      making them easy to detect. Data are compared to those obtained by
      immunofluorescence techniques. Our technique can be used as a preliminary method
      for rapid detection of virus infection using antibodies directed against
      functional proteins.

PMID- 12229931
TI  - Simultaneous evaluation of viability and acrosome integrity of mouse spermatozoa
      using light microscopy.
AB  - Determination of the percentage of live cells with intact acrosomes and no
      morphologic aberrations could be a practical index of semen quality. We applied
      viability and acrosome staining techniques, originally described for bull, boar
      and rabbit sperm, to mouse spermatozoa. The viability stain was either trypan
      blue or Congo red. The stain was precipitated by neutral red in the fixative. The
      acrosome was stained by Giemsa. Sperm morphology, including cytoplasmic droplets,
      could be evaluated as well. The staining method described here is a useful
      routine tool for simultaneous evaluation of the plasma membrane integrity of
      different sperm subdomains, the status of the acrosome, and cellular morphology.

PMID- 12229932
TI  - Standardized staining methods: Feulgen-Rossenbeck reaction for desoxyribonucleic
      acid and periodic acid-Schiff (PAS) procedure.
AB  - A project group working under the European Confederation of Laboratory Medicine
      (ECLM) presents recommendations for standardized procedures for the Feulgen
      Rossenbeck-Schiff and the periodic acid-Schiff (PAS) reactions on cytological and
      histological material. The advantages and disadvantages of such standardized
      procedures are presented here in a preamble. Both users and manufacturers are
      encouraged to give their opinions with a view to achieving consensus on these
      procedures and on how further work on these lines may proceed.

PMID- 12229933
TI  - Localization of neural cell adhesion molecule (N-CAM) immunoreactivity in adult
      rat tissues.
AB  - Neural cell adhesion molecule (N-CAM) mediates homophilic adhesion between cells
      and heterophilic adhesion between cells and extracellular matrix in a Ca2+
      independent manner. N-CAM is widely expressed during development and plays a
      crucial role in cell division, migration, and differentiation, but its expression
      is restricted in adults. The distribution of N-CAM immunoreactivity in adult rat
      tissues was investigated in the present study. N-CAM immunoreactivity was present
      in the nervous system in the molecular layer of the cerebellum, ependymal cells
      surrounding the central canal, axons of the white matter, and in Lamina X of the
      gray matter of the spinal cord. N-CAM immunoreactivity also was found in
      autonomic nerves. In the digestive system, N-CAM immunoreactivity was found in
      the stratified squamous epithelium and nerve plexus of the esophagus, glandular
      cells of the stomach and pylorus, lamina propria, and epithelium of the villi of
      the duodenum, jejunum, and ileum. N-CAM immunoreactivity was demonstrated in the
      secretory cells of the adenohypophysis, islets of Langerhans, and acinar cells of
      the exocrine pancreas. Alveolar cells of the lung were also N-CAM immunoreactive.
      In the urinary system, N-CAM immunoreactivity was seen in the proximal convoluted
      tubules of the kidney. In the male reproductive system, N-CAM immunoreactivity
      was demonstrated in the nerve plexus around the urethral epithelium and in the
      nerve fibers around the smooth muscle cells of the corpus cavernosum penis. In
      the visual system, N-CAM immunoreactivity was seen in the epithelial cells of the
      corpus ciliaris. Cornea and lens epithelium also showed positive
      immunoreactivity. Our results suggest that cells in many tissues and organs of
      the adult rat synthesize N-CAM.

PMID- 12229934
TI  - Comparison of the effects of microwave heating and high pressure cooking for
      antigen retrieval of human and rat Bc1-2 protein in formaldehyde-fixed, paraffin
      embedded sections.
AB  - Immunohistochemical detection of expression of the anti-apoptotic Bcl-2 protein
      is widely studied as a putative prognostic and predictive factor in various types
      of cancer. For that purpose, heating for 10 min by microwave (MW) up t o 100
      degrees C in citrate buffer, pH 6.0, prior to immunostaining is often used to
      retrieve Bcl-2 antigens in archival formalin-fixed, paraffin-embedded tissue. We
      recently reported that Bcl-2 is not only a cytoplasmic protein, but that it is
      present also in interphase nuclei and that it strongly associates with mitotic
      chromosomes. Furthermore, we showed that binding of the monoclonal antibody (MAb)
      #124 with nuclear/chromosomal epitopes is diminished by formaldehyde-based
      fixatives and cannot be restored by MW treatment for 10 min. Here we report that
      prolonged MW heating or heating up to 130 degrees C in a high pressure cooker
      (HPC), despite improved cytoplasmic immunostaining, fails to retrieve
      nuclear/chromosomal Bcl-2 epitopes recognized by the MAb #124 in human tissues.
      In contrast, these procedures can retrieve nuclear/chromosomal Bcl-2 epitopes
      detected by polyclonal #15616E antibodies in rat tissues. The specificity of
      these epitopes was confirmed by Western blot analysis of tissues treated by MW
      heating or HPC.

PMID- 12229935
TI  - Determination of the fraction of S-phase cells in root meristems using
      bromodeoxyuridine labeling.
AB  - The use of bromodeoxyuridine (BrdU) and subsequent immunocytochemical
      visualization for studying cell proliferation in plant meristems was investigated
      in Allium cepa L. root-tips. We describe the optimization of an indirect
      immunoperoxidase method for detecting incorporation of this DNA precursor in
      pulse-labeled cells. The basic object of this study is to quantify the extent to
      which the fraction of S-phase cells can reliably be estimated in asynchronous
      populations. A matrix of parallel labeling schedules with tritiated-thymidine or
      BrdU was developed, and the labeling indices provided by autoradiography or
      immunocytochemistry were compared. Thus, 0.5 mM BrdU assured saturation S-phase
      labeling after an exposure time of 30 min, and the mean length of the S-phase
      determined under such conditions was similar to that previously reported for this
      plant system. Interestingly, Feulgen staining did not interfere with subsequent
      detection of the BrdU probe. This allowed comparative evaluations of the nuclear
      DNA content by Feulgen-microdensitometry and the position of a given cell in G1,
      S or G2 compartments. We also explored the possibility of quantifying BrdU
      incorporation in single nuclei by densitometry measurement of the peroxidase
      label.

PMID- 12229936
TI  - Preclinical evaluation of the Excorp Medical, Inc, Bioartificial Liver Support
      System.
AB  - BACKGROUND: Acute liver failure has no medically recognized effective therapy
      other than orthotopic liver transplantation. Development of bioartificial livers
      for support of patients with acute liver failure requires meaningful preclinical
      evaluation before clinical trials. STUDY DESIGN: Complete results from
      preclinical safety and efficacy evaluation of the Excorp Medical Bioartificial
      Liver Support System (BLSS) using a D-galactosamine (D-gal) canine liver failure
      model are presented. From a total cohort of 23 purpose-bred male hounds, 18
      animals were administered a lethal dose (1.5 g/kg) of D-gal. The 18 animals were
      divided into four treatment groups: no BLSS treatment (n = 6), BLSS treatment
      starting at 24 to 26 hours post D-gal (n = 5), BLSS treatment starting at 16 to
      18 hours post D-gal (n = 4), and "mock support" treatment with a BLSS system
      containing no hepatocytes (n = 3). The animals were treated until death or death
      equivalent, or euthanized at 60 hours. Physiologic parameters were continuously
      monitored. Blood chemistries were obtained every 8 hours. RESULTS: Although
      survival times for BLSS-supported animals were significantly greater than for the
      unsupported group, the greatest impact on delaying progression of liver disease
      was time of intervention. Intervention at 16 to 18 hours post D-gal
      administration showed significant delay in increasing blood ammonia, lactate, and
      prothrombin time as compared with untreated animals. Elevated intracranial
      pressure was found in two of six untreated animals, but in none of the treated
      animals (zero of nine). Healthy animals supported by the BLSS system evidenced no
      significant safety problems. CONCLUSIONS: Results suggest the BLSS impacts the
      course of liver failure in the animal model. Phase I clinical safety evaluation
      is underway.

PMID- 12229937
TI  - Aggressive management of patients with extrahepatic and intrahepatic recurrences
      of hepatocellular carcinoma by combined resection and locoregional therapy.
AB  - BACKGROUND: Resection of hepatocellular carcinoma (HCC) is associated with a high
      incidence of recurrence. Aggressive management of recurrence is an important
      strategy in prolonging survival. This study evaluated the role of combined
      resection and locoregional therapy in the management of selected patients with
      extrahepatic and intrahepatic recurrences. STUDY DESIGN: From a prospective
      database of 399 patients with hepatectomy for HCC from 1989 to 1998, 63 patients
      were identified with extrahepatic and intrahepatic recurrences either
      concurrently or sequentially. Survival outcomes of patients who underwent
      resection of extrahepatic recurrence and re-resection or locoregional therapy for
      intrahepatic recurrence were evaluated. RESULTS: Ten patients underwent resection
      of solitary extrahepatic recurrence and locoregional therapy for intrahepatic
      recurrence. Transarterial chemoembolization was the main treatment modality for
      intrahepatic recurrence. Two of these patients also underwent re-resection of
      intrahepatic recurrence at the time of resection of extrahepatic metastasis.
      Median survival after recurrence of these 10 patients was 44.0 months (range 18.6
      to 132.9 months), and the median overall survival from initial hepatectomy was
      49.0 months (range 21.6 to 134.6 months). In contrast, median survival after
      recurrence of the remaining 53 patients with extrahepatic and intrahepatic
      recurrences treated by nonsurgical means (locoregional therapy, systemic
      chemotherapy, or hormonal therapy) was only 10.6 months (p = 0.002). CONCLUSIONS:
      Aggressive management with combined resection of isolated extrahepatic recurrence
      and re-resection or locoregional therapy for intrahepatic recurrence may offer
      longterm survival in selected patients who develop both intrahepatic and
      extrahepatic recurrences after hepatectomy for HCC.

PMID- 12229938
TI  - Regulation of NFkappaB in hepatic ischemic preconditioning.
AB  - BACKGROUND: The second messengers tyrosine kinase (TK) and protein kinase C (PKC)
      have been implicated in mediating the cellular signaling cascade during hepatic
      ischemic preconditioning (IPC). We evaluated the role of TK and PKC on the
      modulation of the transcription factor nuclear factor kappa B (NFkappaB) and its
      inhibitor IkappaB alpha during IPC. STUDY DESIGN: Yorkshire pigs underwent
      routine harvest. IPC livers underwent 15 minutes of ischemia and 15 minutes of in
      situ perfusion before harvest, with or without pretreatment with a TK inhibitor
      (genistein) or a PKC inhibitor (chelerythrine). During cold storage and
      reperfusion, tissue extracts were analyzed for IkappaB alpha phosphorylation and
      NFkappaB levels and for TK and PKC activity by Western blot. RESULTS: Control pig
      livers demonstrated no change in the levels of TK, PKC, IkappaB alpha, or
      NFkappaB before cold ischemia. IPC grafts demonstrated activation of TK and PKC
      with increased IkappaB alpha phosphorylation and NFkappaB levels before cold
      ischemia. IPC grafts pretreated with genistein demonstrated inhibition of TK
      activation but not of PKC activation. Genistein-pretreated grafts also
      demonstrated inhibition of IkappaB alpha phosphorylation and a lack of NFkappaB
      translocation to the nucleus throughout the entire experiment. IPC grafts
      pretreated with chelerythrine demonstrated inhibition of PKC activation but not
      TK activation. Chelerythrine-pretreated grafts also demonstrated IkappaB alpha
      phosphorylation before cold ischemia and enhanced nuclear levels of NFkappaB.
      CONCLUSIONS: Data suggest that the role of TK in IPC might be mediated in part by
      NFkappaB, but PKC does not depend on NFkappaB for its effect. Two parallel
      signaling pathways might explain these data.

PMID- 12229939
TI  - Overall mortality in the program on the surgical control of the hyperlipidemias.
AB  - BACKGROUND: The Program on the Surgical Control of the Hyperlipidemias (POSCH), a
      secondary intervention trial, was the only lipid/atherosclerosis randomized
      clinical trial that used a surgical modality--partial ileal bypass. POSCH
      provided solid evidence for the clinical and arteriographic benefits of lipid
      profile normalization. Few longterm followup reports have been published in this
      field. This report concerns overall mortality, the primary endpoint of POSCH,
      with a mean followup of 18 years (range 15.5 to 23.0 years). STUDY DESIGN:
      Overall mortality data were compiled from reports to the POSCH clinics, followup
      telephone calls, death certificates, and the US National Death Index. RESULTS:
      There were 144 deaths in the control group (n = 417) and 120 deaths in the
      intervention group (n = 421), using intent-to-treat analysis. The risk reduction
      in the intervention group was 0.201 (20%); the risk ratio was 0.799, or 0.8 (95%
      confidence intervals, 0.628 to 1.018, p = 0.07). The proportion of patients alive
      was 65.7% in the control group and 72.0% in the intervention group, for a
      difference of 6.3% in the intervention group (p = 0.05). Kaplan-Meier survival
      analysis (p = 0.046) and disease-free intervals analysis at 70% survival (p <
      0.001) were confirmatory. The gain in life expectancy in the intervention group
      was 2.7 years. CONCLUSIONS: Longterm followup POSCH data demonstrate that lipid
      profile normalization will decrease overall mortality and will maintain a
      persistent and constant increase in life expectancy.

PMID- 12229940
TI  - Lymph node disorders and prognostic value of nodal involvement in patients
      treated for a borderline ovarian tumor: an analysis of a series of 42
      lymphadenectomies.
AB  - BACKGROUND: The aim of this study is to evaluate the rate and the clinical
      outcomes of lymph node involvement in patients treated for borderline ovarian
      tumor (BOT). STUDY DESIGN: Forty-two patients were treated for BOT with a
      procedure that included lymphadenectomy. Twenty-four patients underwent a pelvic
      lymphadenectomy, 6 a paraaortic lymphadenectomy, and 12 both procedures. Thirty
      two patients underwent systematic lymphadenectomy, five because of associated
      cancer (uterine cervix or corpus) and five because of bulky nodes discovered
      during the surgical procedure. RESULTS: An endosalpingiosis was present in 11
      (26%) patients who underwent lymphadenectomy. Eight patients had nodal
      involvement related to the BOT. All patients with nodal involvement had serous
      BOT with peritoneal implants. None of the patients with a mucinous tumor had
      nodal involvement. None of the patients with early-stage disease (without
      peritoneal disease) had nodal involvement discovered after routine
      lymphadenectomy. None of the patients with nodal involvement died of borderline
      tumor. One patient died of a complication of adjuvant therapy (leukemia after
      chemotherapy). CONCLUSIONS: The prognosis of patients with borderline tumors of
      the ovary and nodal involvement is excellent. Routine lymphadenectomy should not
      be performed in patients with early-stage disease. This procedure should be
      carried out in patients with serous tumor and enlarged lymph nodes.

PMID- 12229941
TI  - Preservation of muscle fascia to decrease lymphedema after complete axillary and
      ilioinguinofemoral lymphadenectomy for melanoma.
AB  - BACKGROUND: In patients with melanoma, there is considerable concern about the
      clearance of clinically negative nodes, partly because of the unacceptable
      morbidity reported after regional lymphadenectomy. The advent of sentinel lymph
      node biopsies has allowed us to select those patients with positive sentinel
      lymph nodes for completion node dissections. The purpose of this article is to
      demonstrate that when complete lymph node dissection is indicated, it can be
      performed with a low risk of lymphedema using the fascia-preserving technique.
      STUDY DESIGN: The records of 209 consecutive patients with melanoma who underwent
      fascia-preserving axillary (n = 116) or ilioinguinofemoral (n = 93)
      lymphadenectomy by a single surgeon between January 1984 and April 1998 were
      reviewed. In each operation, care was taken not to disrupt the muscle fascia at
      the site of lymphadenectomy. RESULTS: In the fascia-preserving axillary group,
      there were 59 men and 47 women with mean age of 53 years (range 21 to 79 years).
      There were three recurrences (3%) outside the borders of dissection. Transient
      upper extremity edema (8%) resolved over a median of 5 months, and permanent
      upper extremity edema occurred in 5% of patients. In the ilioinguinofemoral
      group, there were 19 men and 37 women with a mean age of 52 years (range 21 to 88
      years). There was one recurrence (2%) outside the borders of dissection.
      Transient lower extremity edema (48%) resolved over a median of 12 months, and
      permanent lower extremity edema occurred in 14% of patients. CONCLUSIONS:
      Preservation of the muscle fascia during lymph node dissection results in a lower
      incidence of permanent edema, with no increased risk of recurrence.

PMID- 12229942
TI  - Longterm followup of posthysterectomy vaginal vault prolapse abdominal repair: a
      report of 85 cases.
AB  - BACKGROUND: There are many surgical procedures to treat posthysterectomy vaginal
      vault prolapse. Abdominal sacral colpopexy is one of these procedures. The aim of
      this study was to review the cases of 85 consecutive patients treated by this
      technique since 1978 by the same surgical team using the same procedure. Our
      surgical procedure will be explained. STUDY DESIGN: Eighty-five patients were
      treated in our department between 1978 and 1998 for posthysterectomy vaginal
      vault prolapse. The mean age was 55.42 years. The mean weight was 63.37 kg. Their
      parity ranged from 0 to 5 (mean, 2.54). The interval of time between hysterectomy
      and vaginal vault prolapse repair ranged from 1 to 37 years (mean, 17.92 years).
      The main indication for hysterectomy was uterine leiomyomas. Of these patients,
      67.05% had stress urinary incontinence, and mean urethral closure pressure was
      48.7 cm H2O. All patients had abdominal sacral colpopexy associated with a Burch
      procedure and a posterior perineal repair. RESULTS: Seventeen patients had
      postoperative fever. Twenty-two had urinary tract infections. Two patients had to
      undergo blood transfusion. Three patients had postoperative urinary retention.
      The median longterm followup was 10.5 years; 27.05% of patients had relapsing
      stress urinary incontinence. Two patients had a relapse of the vaginal vault
      prolapse. CONCLUSIONS: The abdominal sacral colpopexy is a safe operation with
      low morbidity and long-standing good results. It can be recommended for sexually
      active women. Nevertheless, the Burch procedure performed with this operation
      failed to prevent recurrence of urinary incontinence.

PMID- 12229943
TI  - Unresectable liver metastases.

PMID- 12229944
TI  - What's new in ophthalmic surgery.

PMID- 12229945
TI  - What's new in general surgery: endocrine surgery.

PMID- 12229946
TI  - Attrition of advanced trauma life support (ATLS) skills among ATLS instructors
      and providers in Mexico.
AB  - BACKGROUND: Mexico has had the Advanced Trauma Life Support (ATLS) program since
      1986. We assessed the attrition of ATLS skills among ATLS providers and
      instructors in this country. STUDY DESIGN: Three groups (S, 16 students [new
      medical graduates enrolled for an ATLS course]; P, 33 providers; and I, 26
      instructors [who had completed courses previously]) were evaluated. Group S read
      the manual before pretesting. Groups P and I were subdivided based on the length
      of time since the course had been completed: P1, less than 2 years (n = 22); P2,
      more than 2 years (n = 11); I1, less than 2 years (n = 16); and I2, more than 2
      years (n = 10). Multiple-choice and psychomotor testing using ATLS scoring
      criteria were used. Affect was assessed post-ATLS for motivational factors,
      interactivity, and attitude toward trauma care. RESULTS: Multiple-choice test
      scores (means +/- SD) out of a maximum of 40 were as follows: S, 24.3 +/- 2.6;
      P1, 24.0 +/- 5.7; P2, 21.3 +/- 8.0; I1, 23.2 +/- 8.2; and I2, 24.0 +/- 7.2. Group
      S all passed the post-ATLS multiple-choice test (with correct answer percentages
      of 60.3% +/- 6.6% pre-ATLS versus 88.8% +/- 5.6% post-ATLS). An ATLS passing
      score of 80% correct answers was achieved in 2 of 33 for group P and 8 of 26 for
      group I (p < 0.05), with no statistically significant differences between groups
      P1 and P2 or between groups I1 and I2. For the psychomotor skills testing
      component, 5 of 16 in the S group passed, 15 of 22 in P1 passed, 9 of 11 in P2
      passed, 14 of 16 in I1 passed, and 6 of 10 in I2 passed. The pass rate was
      significantly lower in the S pre-ATLS group than in the P and I groups (p < 0.05,
      Fisher's exact test). More than 60% preferred interactive components and enrolled
      for professional improvement, and more than 90% reported improved post-ATLS
      attitude to trauma care. CONCLUSIONS: Reading the manual alone yields similar
      cognitive but inferior psychomotor performance compared with subjects who
      completed the course previously. The majority of previous providers and
      instructors did not obtain a passing score (80%) in the multiple-choice test, but
      all the new providers passed the post-ATLS multiple-choice test, suggesting major
      attrition of cognitive skills but maintenance of psychomotor skills. Instructors
      had superior cognitive performance versus providers with worsening performance
      over time, but clinical skills performance was maintained at an equally high
      level by all groups. A very positive attitude toward ATLS prevailed among all
      participants.

PMID- 12229947
TI  - Radiofrequency ablation of unresectable liver metastases.

PMID- 12229948
TI  - Pelvic radiation and anorectal function: introducing the concept of sphincter
      preserving radiation therapy.

PMID- 12229949
TI  - The theories and realities of port-site metastases: a critical appraisal.

PMID- 12229950
TI  - Decision making in palliative surgery.
AB  - BACKGROUND: Palliative surgery for advanced cancer patients involves complex
      decision making. Surgeons with a cancer-focused practice were surveyed to
      determine the extent to which palliative surgery was currently practiced, to
      identify ethical dilemmas and barriers they faced in performing palliative
      surgery, and to evaluate their treatment choices in four different clinical
      scenarios. STUDY DESIGN: A 110-item survey was devised after extensive review of
      the palliative care and palliative surgery literature to evaluate current
      practices and attitudes regarding palliative surgery. Case vignettes were devised
      to evaluate dinical factors influencing surgeons' selection of treatment for
      symptomatic patients with advanced malignancy. RESULTS: Survey response rate was
      24% (419 of 1,740). Respondents reported 74% of their surgery caseload as cancer
      related, and 21% of these as palliative. On a scale of 1 (uncommon problem) to 7
      (common problem), surgeons reported that the most common ethical dilemmas in
      palliative surgery were providing patients with honest information without
      destroying hope (5.6 +/- 1.4) (mean +/- standard deviation), and preserving
      patient choice (5.0 +/- 1.7). Bound on error of the average frequency estimate
      for ethical dilemmas, based on response rate, was 0.08. On a scale of 1 (not a
      barrier) to 7 (a severe barrier), surgeons rated the most severe barriers to
      optimum use of palliative surgery as limitations of managed care (4.1 +/- 2.0)
      and referral to surgery by other specialists (3.9 +/- 1.8). Bound on error of the
      estimate for average severity of barriers, based on response rate, was 0.09. They
      rated the least severe barriers to palliative surgery as surgeon avoidance of
      dying patients (3.0 +/- 1.8) and surgery department reluctance to perform
      palliative surgery (2.6 +/- 1.6). Analysis of surgeons' treatment selection in
      case vignettes indicated that patient age, aggressiveness of tumor biology, local
      extent of disease, and severity of patient symptoms were all variables of
      influence for treatment selection in patients with advanced malignancies.
      CONCLUSIONS: Palliative surgery involves numerous ethical dilemmas, the most
      prominent being providing honest information to patients without destroying hope,
      and complex treatment decision making. We have identified variables of major
      influence to surgeons in the palliative treatment selection for patients with
      advanced, solid malignancies. Validation of these variables as meaningful will
      require future studies focusing on patient outcomes.

PMID- 12229951
TI  - Microcystic adenomas of the pancreas.

PMID- 12229952
TI  - Grade V renal injury: avulsion of the renal pedicle.

PMID- 12229953
TI  - Percutaneous radiofrequency ablation of lung neoplasms: a minimally invasive
      strategy for inoperable patients.

PMID- 12229954
TI  - A new method for laparoscopic percutaneous tube gastrostomy with a single 1-cm
      long incision for patients with esophageal obstruction.

PMID- 12229955
TI  - Fatal thyroid crisis years after two thyroidectomies for graves' disease: is
      thyroid tissue autotransplantation for postthyroidectomy hypothyroidism
      worthwhile?

PMID- 12229956
TI  - Management of dyspnea at the end of life.

PMID- 12229957
TI  - Nonparasitic splenic cysts.

PMID- 12229958
TI  - The magnitude of association between Helicobacter pylori infection and the
      development of gastric cancer.

PMID- 12229959
TI  - Bowel ultrasound in Crohn disease: current role and future applications.

PMID- 12229960
TI  - Eradication of Helicobacter pylori does not increase acid reflux in patients with
      mild to moderate reflux oesophagitis.
AB  - BACKGROUND: A substantial minority of patients with gastro-oesophageal reflux
      disease (GERD) are infected with Helicobacter pylori, but there is controversy as
      to whether these patients should be treated for their infection. We hypothesized
      that H. pylori eradication increases gastro-oesophageal acid reflux in such
      patients with time. METHODS: Thirty-five consecutive H. pylori-infected patients
      (16 M and 19 F) with mild or moderate reflux oesophagitis were enrolled. Twenty
      four-hour intra-oesophageal (n = 35) and intragastric (n = 12) pH-metry was
      recorded before and 15 months after H. pylori eradication. Gastric biopsy
      specimens from the antrum and corpus were obtained from 10 consecutive patients
      before and 15 months after H. pylori eradication. RESULTS: Fifteen months after
      eradication of H. pylori there was a significant decrease in percentage time
      oesophageal pH < 4 in the recumbent position only (P = 0.04). Despite a marked
      reduction in the severity of gastritis, there was no significant change in
      gastric acidity, total intra-oesophageal acid exposure or symptom score.
      Heartburn improved in 12, worsened in 7. and remained unchanged in 16 patients (P
      = 0.36) without any significant relationship to individual changes in acid
      exposure (P = 0.60). CONCLUSIONS: H. pylori eradication does not increase gastric
      acidity or gastro-oesophageal acid reflux in patients with mild to moderate
      reflux oesophagitis over the first 15 months.

PMID- 12229961
TI  - Does the method of Helicobacter pylori detection influence the association with
      gastric cancer risk?
AB  - BACKGROUND: The exact role of Helicobacter pylori as a causative agent of gastric
      cancer is still under debate. The aim of this study was to determine how the use
      of different diagnostic methods for detection of H. pylori influences the
      measures of prevalence of the infection and thus the association with risk of
      gastric adenocarcinoma. METHODS: We included 72 cases and 324 controls in an
      endoscopy clinic-based matched case-control study. Culture of H. pylori and
      immunohistochemical staining were performed on gastric biopsies. Serum samples
      were tested for H. pylori IgG by conventional ELISA and by immunoblotting.
      RESULTS: The overall prevalence of H. pylori was 68% based on all 4 diagnostic
      methods, 79% in the cases and 66% in the controls. Highest agreement, 91%, was
      observed between culture and immunohistochemistry with a Kappa value of 0.81.
      Immunoblotting detected the highest number of H. pylori-positive subjects in both
      cases and controls. The association of H. pylori positivity with gastric cancer
      was generally weaker and statistically non-significant using culture and
      immunohistochemistry compared with the serological tests, of which IgG ELISA
      yielded the higher odds ratio (OR 2.5, 95% confidence interval 1.4-4.4).
      CONCLUSION: The study shows that relative risk estimates for the association
      between H. pylori and gastric cancer risk are to some extent determined by the
      diagnostic method used to detect H. pylori infection.

PMID- 12229963
TI  - Risk factors for the severity of erosive esophagitis in Helicobacter pylori
      negative patients with gastroesophageal reflux disease.
AB  - BACKGROUND: The risk factors for the varying grades of erosive esophagitis (EE)
      severity could be better understood. For that reason. we evaluated the risk
      factors associated with EE in patients with gastroesophageal reflux disease.
      METHOD: We determined the presence and severity of EE (using the Los Angeles
      Classification) in patients with negative serology Helicobacterpylori who
      underwent esophagogastroduodenoscopy as part of screening in four prospective,
      multicenter, randomized, double-blind comparative trials of once-daily
      esomeprazole and omeprazole for the acute healing of erosive esophagitis. We also
      examined the baseline characteristics of enrolled patients, and identified risk
      factors for severe disease using a multivariable logistic regression model.
      RESULTS: Erosive esophagitis was documented in 6709 patients of a total of 10,294
      patients who underwent endoscopy: of these. 34% had grade A. 39% had grade B. 20%
      had grade C. and 7% had grade D disease. The majority of patients were male (61%)
      and Caucasian (93%) with a mean age of 46 years. In the regression model, the
      following were significant independent risk factors for severe (grades C and D)
      versus mild erosive esophagitis (grades A and B): severe heartburn (adjusted odds
      ratio 1.79); prolonged heartburn > 5 years in duration (1.16); obesity (1.21);
      the presence of hiatus hernia (2.13); male gender (1.97); and Caucasian ethnicity
      (1.53). CONCLUSION: In this large sample of patients with predominantly H. pylori
      negative gastroesophageal reflux disease, risk factors for severe erosive
      esophagitis were the duration and severity of heartburn, and obesity.

PMID- 12229962
TI  - Helicobacter pylori and CagA status, serum gastrin, interleukin-8 and gastric
      acid secretion in gastric cancer.
AB  - BACKGROUND: Despite numerous epidemiological studies, the association between
      Helicobacter pylori infection and gastric cancer (GC) remains unexplained. This
      study was designed to determine the seropositivity of H. pylori and cytotoxin
      associated gene A (CagA), serum gastrin and interleukin-8 (IL-8) levels as well
      as basal intragastric pH and maximal histamine-induced gastric acid outputs (MAO)
      in a large series of GC patients and controls. METHODS: 337 GC patients (118 men
      and 219 women; median age 59.4; range 21-87) and 337 controls randomized for sex
      and age entered the study. Serum IgG antibodies to H. pylori and CagA and serum
      levels of IL-8 were measured by enzyme-linked immunosorbent assay, while serum
      amidated gastrin was determined by specific radioimmunoassay and correlated with
      gastric luminal pH. RESULTS: The numbers of GC patients and controls involved in
      the study in various age groups, ranging from 20 to > 70 years, were similar, but
      overall H. pylori IgG seropositivity in GC patients was significantly higher
      (90.8%) than in controls (79.2%). The overall CagA seropositivity in GC patients
      was about double (58.2%) that in controls (25.2%). Serum gastrin levels over the
      calculated cut-off value (38.88 pM/L) were found in several-fold larger number in
      GC patients (48%) than in controls (8.3%) and. similarly, serum IL-8 values over
      the cut-off point (1.77 pg/mL) occurred in almost all (99.7%) GC patients but in
      only a few controls (0.3%). Basal intragastric pH above the cut-off point (pH =
      4.50) was observed in about 58.2% of GC patients compared to 15.1% in controls,
      and strong correlation between the serum gastrin and gastric pH was found in GC
      but weak in controls. The cut-off value for MAO was 12.3 mml/h; MAO below this
      cut-off value occurred in 89.9% of GC patients and in only 4.7% of controls. A
      summary odds ratio (SOR) in GC for H. pylori IgG was 2.59 (95% Cl: 1.61-4.22) for
      CagA - 4.12 (95% Cl; 2.93-5.8), for serum gastrin - 10.25 (95%; 6.47-16.47) and
      for MAO - 15.2 (95% Cl; 9.45-39.82). Multivariable analysis of serum gastrin, IgG
      and CagA, and luminal pH and MAO values revealed that only gastrin and CagA have
      significant influence on GC formation (OR > 1 in logistic regression).
      CONCLUSIONS: 1. CG patients show significantly higher H. pylori IgG and CagA
      seropositivity than dyspeptic age- and gender-matched controls, confirming that
      gastric infection with CagA expressing H. pylori greatly increases the risk of
      GC. 2. Serum gastrin levels in GC but not in controls are correlated with the
      rise in intragastric pH, indicating that excessive gastrin release in GC is
      affected by lower intragastric pH. 3. Serum gastrin level and CagA seropositivity
      are significantly increased in the majority of GC patients, and are the only
      variables in multivariable analysis to have a predominant influence on GC
      formation, which suggests that both these parameters may be implicated in H.
      pylori-related gastric carcinogenesis. 4. H. pylori-infected GC patients produce
      significantly more IL-8 than do non-GC controls, probably reflecting CagA
      positive H. pylori-associated gastritis.

PMID- 12229964
TI  - Long-term outcome of functional dyspepsia: effect of Helicobacter pylori
      infection. A 6- to 7-year follow-up study.
AB  - BACKGROUND: Dyspepsia accounts for substantial healthcare costs from medication
      use and expensive investigations, because most patients with upper abdominal
      complaints have functional dyspepsia. The role of Helicobacter pylori infection
      in functional dyspepsia is still controversial. The aim of this study was to
      investigate the effect of H. pylori infection on the natural history of
      functional dyspepsia and to evaluate the diagnostic yield of repeat examinations.
      METHODS: Unselected patients with dyspepsia in general practice were thoroughly
      investigated at baseline. Patients with functional dyspepsia were enrolled in
      this long-term follow-up study. The medical history of each patient was reviewed
      after 6 to 7 years, and the total number and outcome of repeat investigations
      recorded. Study patients filled in a dyspepsia questionnaire and were invited for
      voluntary gastroscopy at the end of follow-up. RESULTS: Of 205 eligible patients,
      201 were finally enrolled in this study (118 H. pylori-positive and 83 H. pylori
      negative). No malignancies explaining the patients' symptoms were found during
      follow-up. Only four cases of peptic ulcer disease were found in H. pylori
      infected patients, i.e. an annual incidence of less than 1%. During the follow-up
      period, H. pylori-positive patients were investigated by endoscopy more often
      (47%) than H. pylori-negative patients (29%) (P = 0.011) with comparable findings
      in follow-up examinations. CONCLUSION: Functional dyspepsia is a long-lasting
      disorder with an excellent prognosis regardless of H. pylori infection.

PMID- 12229966
TI  - Empiric clustering of dyspepsia into symptom subgroups: a population-based study.
AB  - BACKGROUND: Different definitions of dyspepsia are applied by researchers yet
      measurement of the influence of these on prevalence estimates is uncertain.
      Despite continued debate regarding dyspepsia subgroups, few studies have used a
      data-drive approach to assess the existence and relevance of symptom clusters. We
      aimed to address both these issues. METHODS: A random population sample (n =
      2300) identified in New South Wales. Prevalence estimates of dyspepsia were
      calculated by applying four standardized dyspepsia definitions. Principal
      components analyses, using firstly the presence/absence of symptoms and then
      secondly severity of symptoms, were undertaken to determine if symptom factors
      existed. RESULTS: Prevalence estimates ranged from 11% to 36%. Similar prevalence
      rates for men and women were observed for all definitions except Rome II. Over
      one-third of respondents nominated heartburn or epigastric pain as their most
      bothersome symptom. However, 22% of respondents were unable to answer this
      question. The principal components analysis produced four symptom factors: a
      nausea factor, dysmotility-like dyspepsia (early satiety and fullness), ulcer
      like (epigastric pain and bloating) and reflux-like (heartburn and acid
      regurgitation). However, the factors accounted for less than 50% of the variance.
      Similar factors were identified in men and women for dysmotility-like and reflux
      like dyspepsia. Use of presence/absence or severity of symptoms made little
      difference to the symptom factors produced or the amount of variance explained.
      CONCLUSIONS: The prevalence of dyspepsia depends on the definition applied. While
      there is some empirical evidence of symptom subgroups, they appear to be of
      little clinical utility.

PMID- 12229965
TI  - A population-based study on bowel habits in a Swedish community: prevalence of
      faecal incontinence and constipation.
AB  - BACKGROUND: The self-reported bowel habits and the prevalence of faecal
      incontinence and constipation in men and women between the ages of 31 and 76 are
      assessed. METHODS: A postal questionnaire was sent to a random sample (n = 2000)
      of the total population of persons between the ages of 31 and 76 living in the
      County of Ostergotland, Sweden. RESULTS: The response rate was 80.5%. Overall,
      67.8% reported one bowel movement per day and 4.4% had more than 21 or less than
      3 bowel movements per week. This means that 95.6% had between 3 bowel movements a
      day to 3 bowel movements a week. Among women, 4.3%, and among men. 1.7%, reported
      less than 3 bowel movements per week. Women and men used the same terms to
      describe the definition of constipation. Women had a significantly higher self
      reported prevalence of constipation than men (P < 0.0001). About 20% of all women
      considered themselves constipated. The use of laxatives increased with age and
      22% and 10% of elderly women and men, respectively, used laxatives including
      bulking agents for at least every fourth toilet procedure. About 10% reported
      leakage of faeces more often than once a month in the case of loose stools. With
      solid faeces, the rate of leakage was 1.4% and 0.4% for women and men,
      respectively. Soiling of underclothes more than once a month occurred in 21% of
      men and in 14.5% of women (P = 0.006) and involuntary daily leakage of gas in
      5.9% of men and 4.9% of women (n.s.). CONCLUSIONS: Constipation and faecal
      incontinence are common problems in a general Swedish population.

PMID- 12229967
TI  - Lack of correlation between disease activity and decreased stimulated secretion
      of IL-10 in lymphocytes from patients with celiac disease.
AB  - BACKGROUND: Celiac disease (CD) is commonly believed to be a predominantly Th1
      disease. However, the exact balance between the Th1 and Th2 arms, as well as the
      correlation to clinical parameters, remains unclear. The aim was to assess the
      Th1/Th2 cytokine profile and its correlation to clinical parameters in active and
      non-active CD patients. METHODS: Peak, total secretion and secretory pattern of
      the Th1 cytokines (IFN-gamma and IL-2) and Th2 cytokines (IL-4 and IL-10) were
      determined in resting and stimulated peripheral blood mononuclear cells (PBMC)
      from 19 CD patients with active and non-active disease and 20 normal controls.
      RESULTS: Peak and total secretion of IL-10 were significantly reduced in CD
      patients compared with normal controls. This was due to a persistently flat
      secretory pattern of IL-10 over time in CD patients. In addition, IFN-gamma/IL-10
      and the IL-2/IL-10 ratios of peak and total secretion were higher in patients
      than in controls. In contrast, peak, total secretion and secretory pattern of IL
      2, IFN-gamma and IL-4 were comparable in patients and controls as well as the IL
      2/IL-4 and IFN-gamma/IL-4 ratios. No difference in the cytokine secretion or
      Th1/Th2 ratio was found between active and non-active patients or between
      pediatric and adult patients. CONCLUSIONS: These data indicate that the Thl/Th2
      balance in CD is shifted towards Th1 cytokines because of a down-regulated IL-10
      secretion. The aberrant profile of cytokine secretion of these patients is not
      associated with clinical parameters and suggests an inherent defect in IL-10
      secretion in CD.

PMID- 12229968
TI  - Coeliac disease candidate genes: no association with functional polymorphisms in
      matrix metalloproteinase 1 and 3 gene promoters.
AB  - BACKGROUND: Coeliac disease is polygenic with a large genetic component. Matrix
      metalloproteinase-1 (MMP-1) and MMP-3 degrade extracellular matrix; expression
      levels are increased in the coeliac lesion where tissue damage is observed.
      Polymorphisms associated with elevated expression (MMP-3 -1171 allele 5A; MMP-1 
      1607 2G), at 11q22.2, a region repeatedly showing evidence of linkage in coeliac
      disease, are associated with other chronic inflammatory disorders which may share
      a common molecular pathology. We tested for an association between these
      candidate gene polymorphisms and coeliac disease. METHODS: Two independent
      collections of 225 and 102 combined (Norwegian and Swedish) simplex families, and
      160 independent healthy controls from the Norwegian Bone Marrow Donor Registry
      were used. Each individual was genotyped by PCR and fragment length analysis on
      an automated sequencer. The transmission/disequilibrium test was applied. Odds
      ratios were calculated employing probands or affected sibs where available, as
      cases versus independent controls. RESULTS: MMP-1 allele 2G did not show evidence
      of association in any tests undertaken. Neither did we find evidence for
      association of MMP-3 allele 5A, except among the combined family data: a non
      significant tendency toward reduced risk was observed among males carrying MMP-3
      allele 5A (40.2% transmission, Pc = 0.2). Further testing to clarify this
      observation did not reveal a significant association (odds ratio = 0.67 (95%
      confidence interval: 0.42-1.07), P = 0.08). CONCLUSIONS: We did not find
      significant evidence to support an association of MMP-3 allele 5A or MMP-1 allele
      2G with coeliac disease in Norwegian and Swedish populations.

PMID- 12229969
TI  - Functional relevance of activin A in the intestinal epithelium.
AB  - BACKGROUND: Activin A modulates inflammation and repair in various tissues. The
      aim of this study was to characterize the effects of activin A on intestinal
      epithelial cell function and to evaluate a potential role in intestinal
      epithelial wound repair and inflammation. METHODS: The expression of activin A
      and its receptors ActRI and ActRII in intestinal epithelial IEC-6 cells and in
      tissues from IBD patients and non-inflamed controls was evaluated using RT-PCR
      and immunohistochemistry. Functional effects of activin A on intestinal
      epithelial cell migration and proliferation were assessed using an in vitro
      wounding model and colorimetric MTT assays. RESULTS: Expression of the activin
      betaA subunit and the activin receptors ActRI and ActRII in IEC-6 cells was
      demonstrated using RT-PCR. Activin A (50 ng/ml) caused a significant, on average
      2.8-fold enhancement of epithelial cell migration and a significant on average
      4.1-fold inhibition of IEC-6 cell proliferation. Expression of ActRI and ActRII
      was observed in all intestinal tissues from patients with IBD and in all
      controls. In contrast, no expression of the activin betaA-subunit was observed in
      controls, while betaA expression was found in intestinal tissues from IBD
      patients. CONCLUSIONS: Activin A may play an important role in the modulation of
      intestinal epithelial cell function, thus providing a new approach to modulate
      intestinal wound repair.

PMID- 12229970
TI  - Constitutive expression of inducible nitric oxide synthase in the normal human
      colonic epithelium.
AB  - BACKGROUND: Inducible nitric oxide synthase (iNOS) in the human colon is
      considered expressed only in inflammatory states such as ulcerative or
      collagenous colitis. As subtle iNOS labelling was previously observed in some
      colonic mucosal biopsies from a heterogeneous group of controls with non-inflamed
      bowel, we studied whether bowel preparation with bisacodyl or polyethylene glycol
      prior to sigmoidoscopy might induce iNOS expression. METHODS: Ten healthy, non
      smoking male subjects were investigated. Mucosal biopsies were taken from the
      sigmoid colon prior to bowel preparation and again 12 h after rectal
      administration of bisacodyl or polyethylene glycol in randomized order.
      Expression of iNOS protein was quantified by Western blot analysis and localized
      by immunohistochemistry. RESULTS: iNOS was expressed in the colonic mucosal
      biopsies from all subjects and localized in the epithelial cells, particularly at
      the luminal border of the epithelial cells and more pronounced in the crypt
      epithelium. The expression of iNOS was unaffected by bowel preparation with
      bisacodyl or polyethylene glycol. CONCLUSIONS: iNOS is constitutively expressed
      in the normal colonic epithelium. The results suggest that synthesis of iNOS
      protein is unaffected by bowel preparation with the secretagogue laxative,
      bisacodyl, or polyethylene glycol.

PMID- 12229971
TI  - Cirrhotic patients with or without hepatocellular carcinoma harbour AFP-specific
      T-lymphocytes that can be activated in vitro by human alpha-fetoprotein.
AB  - BACKGROUND: Alpha-fetoprotein (AFP) is re-expressed in 60%-70% of hepatocellular
      carcinomas (HCC) and may therefore be a potential target for a prophylactic or
      therapeutic tumour-specific vaccination. A prerequisite for this approach is the
      possibility to induce AFP-specific T-lymphocytes in patients with HCC and/or
      cirrhosis. METHODS: Peripheral blood was examined for the presence of AFP
      specific T-lymphocytes using a FACS-based interferon-gamma secretion assay.
      RESULTS: In a group of healthy volunteers, the presence of AFP-specific CD4- and
      CD8-lymphocytes was demonstrated. Screening of blood of 14 cirrhotic patients
      without HCC and 23 cirrhotic patients with HCC showed that patients with liver
      diseases that represent targets for vaccination also harbour CD4-positive as well
      as CD8-positive AFP-specific Tlymphocytes. AFP reactivity in patients'
      lymphocytes was not significantly influenced by soluble serum AFP. The median
      stimulation factors for CD4-positive T-lymphocytes were significantly higher (P =
      0.0365) in cirrhotic patients without HCC (median 2.08, range 0.50-4.40) compared
      to cirrhotic patients with HCC (median 1.15, range 0.24-8.50). CONCLUSION: AFP
      specific T-lymphocytes that may be instrumental in HCC vaccination strategies are
      present in humans. This study suggests that immunopreventive vaccination of
      cirrhotic patients rather than immunotherapeutic vaccination of HCC patients may
      be preferable.

PMID- 12229972
TI  - Analysis of pancreaticobiliary ductal union based on intraoperative
      cholangiography in patients undergoing laparoscopic cholecystectomy.
AB  - BACKGROUND: In order to diagnose pancreaticobiliary maljunction (PBM), it is
      necessary to perform direct fluoroscopic examinations of the biliary tract
      system. For patients with benign biliary diseases, these examinations are
      performed only in selected cases, because they are generally invasive. We
      investigated whether intraoperative cholangiography was practicable in evaluating
      the presence of PBM in patients with benign biliary diseases who underwent
      laparoscopic cholecystectomy (LC). METHOD: Between March 1998 and February 2001,
      intraoperative cholangiography (IOCG), which is one of the direct fluoroscopic
      examinations, was attempted in all 100 patients who underwent LC. RESULTS: IOCG
      was completed successfully in 98 patients (98.0%). No complications associated
      with IOCG occurred. In 13 (13.3%) of 98 patients, IOCG showed reflux of contrast
      medium into the pancreatic duct through a common channel. 'A long common channel'
      was observed in 8 cases (8.2%), suggesting the presence of PBM. CONCLUSION: These
      results suggest that IOCG in LC may be a practicable method for detecting the
      presence of PBM.

PMID- 12229973
TI  - Intrahepatic heterogeneity of hepatic venous pressure gradient in human
      cirrhosis.
AB  - BACKGROUND: The hepatic venous pressure gradient (HVPG) is used to evaluate
      portal hypertension. METHODS: We measured HVPG in two separate liver veins in 169
      liver vein catheterizations in 102 cirrhosis patients and in 27 patients with no
      liver disease (controls). RESULTS: In the controls, the two measurements differed
      by 0.0 +/- 1.8 mmHg (mean +/- s, n = 27), upper 95% confidence limit 3.6 mmHg
      (mean + 2 s). HVPG ranged from -0.1 to 8.3 mmHg, upper 95% confidence limit 6.7
      mmHg. In cirrhosis, the two measurements agreed within +/- 3.6 mmHg in 39%. In
      61%, the measurements differed by 4-34 mmHg. In 35%, fluoroscopy demonstrated
      hepatic vein-to-hepatic-vein shunting in veins with low HVPG values. In some
      patients with HVPG measurements above 30 mmHg, Doppler ultrasound examination
      showed arterialization of the hepatic vasculature. DISCUSSION: Our results
      demonstrate a hitherto unrecognized notable heterogeneity of the intrahepatic
      vasculature and HVPG measurements in cirrhosis. The presumption of interposition
      of non-flowing blood between the catheter tip and the portal system for the
      measurement of HVPG may thus be violated in about one-third of the cirrhosis
      cases because of abnormal outlet into hepatic venous shunts and in a minor
      fraction because of abnormal arterial inlet. In 26%, one measurement was below 12
      mmHg, the other measurement above. If the HVPG had been measured in only one
      liver vein, 13% of the cases would have been classified in a lower risk group
      than appropriate according to the 12 mmHg concept of risk of bleeding from
      oesophageal varices.

PMID- 12229974
TI  - Changes in bile acid composition and effect on cytolytic activity of fecal water
      by ursodeoxycholic acid administration: a placebo-controlled cross-over
      intervention trial in healthy volunteers.
AB  - BACKGROUND: Ursodeoxycholic acid (UDCA) has been shown to affect membrane
      damaging effects of bile acids in vitro and fecal bile acid composition in rats.
      This study evaluates the effect of UDCA on fecal bile acid composition and on
      cytolytic activity of fecal water in man to clarify the potential chemopreventive
      role of UDCA for colorectal cancer. METHODS: In this placebo-controlled crossover
      intervention trial, the effect of 900 mg/day UDCA orally in 15 healthy volunteers
      was studied. At the end of each 4-week period, 72 h feces were collected. Total
      and individual bile acids in feces were determined by gas chromatography and
      soluble bile acids were analyzed by high-performance liquid chromatography.
      Cytolytic activity of fecal water was measured using an erythrocyte lysis assay.
      RESULTS: In feces, the percentages of primary bile acids-cholic acid (CA) and
      chenodeoxycholic acid (CDCA)-and of secondary bile acid-deoxycholic acid (DCA) -
      decreased after supplementation with UDCA, whereas those of UDCA and LCA
      increased from 2.7 +/- 0.4% to 23.7 +/- 2.6%, P < 0.0001 and from 26.2 +/- 1.2%
      to 49.4 +/- 1.8%, P < 0.0001 respectively. The concentrations of these two bile
      acids in fecal water also increased after UDCA administration from 7.8 +/- 1.9
      micromol/l to 47.0 +/- 6.7 micromol/l (UDCA), P < 0.0001 and from 2.5 +/- 0.6
      micromol/l to 18.3 +/- 4.1 micromol/l (LCA), P < 0.002, respectively. Cytolytic
      activity of fecal water was not affected by UDCA. CONCLUSION: These results do
      not support a protective effect of UDCA supplementation against colorectal cancer
      in man.

PMID- 12229975
TI  - Monitoring of tumour glucose metabolism by PET in a phase I study evaluating
      hormonal therapy in advanced pancreatic cancer.
AB  - BACKGROUND: Positron emission tomography (PET) determines therapy-induced changes
      in tumour glucose utilization. Experimental data indicate that cholecystokinin
      (CCK) stimulates pancreatic cancer growth. In this study in patients with
      advanced pancreatic cancer, we evaluated the use of fluorodeoxyglucose (FDG) PET
      compared with magnetic resonance imaging (MRI) in monitoring hormonal therapy
      using a highly selective, non-peptide CCK receptor antagonist (SR 27897B).
      METHODS: Nineteen patients were enrolled on a 28-day course of SR 27897B.
      Initially, 4 patients received 20 mg of SR 27897B; 9 patients received 40 mg; and
      6 patients 80 mg. Imaging studies, including FDG-PET and MRI, were performed at
      baseline and on days 14 and 28. RESULTS: No significant changes in FDG uptake by
      the primary tumours were observed. Rate of progression of disease was 11 (61%) of
      18 evaluable patients by MRI. Median survival of all patients enrolled was 2.7
      months. SR 27897B was fairly well tolerated at all doses tested. The most common
      side effects were gastrointestinal disorders such as diarrhoea, flatulence and
      nausea. CONCLUSION: SR 27897B, when used alone at the limited doses employed, led
      neither to an impairment of tumour glucose metabolism nor to a reduction of
      tumour size in advanced pancreatic cancer.

PMID- 12229976
TI  - Cigarette smoking and adult coeliac disease.
AB  - BACKGROUND: While coeliac disease is clearly induced by dietary gluten ingestion
      in genetically susceptible individuals, other environmental factors may influence
      the onset of disease. Two studies have suggested that cigarette smoking has a
      protective role, but a third has not. METHODS: We examined the relationship
      between cigarette smoking and coeliac disease in individuals with coeliac disease
      diagnosed in adulthood from two large population-based disease registers and age
      and sex-matched controls from local general practitioner lists. Participants were
      mailed a three-page lifestyle and general health questionnaire. Smoking habits of
      coeliacs were compared with controls and with habits reported in the Health
      Survey for England 1995. RESULTS: An inverse association between current smoking
      and adult coeliac disease was identified (odds ratio: 0.77 (95% CI 0.56-1.06))
      and remained when comparing ever smoked versus never smoked (odds ratio: 0.83
      (0.68-1.00)). When the smoking habits of the coeliacs were compared with the
      national figures, the number of coeliacs who currently smoked was 40% lower than
      expected (smoking ratio 0.60, 0.46-0.78). This inverse association was accounted
      for by the behaviour of the 35-54-year age group (odds ratio for ever smoked 0.67
      (0.51-0.89)). There was no association with having ever smoked in the younger age
      group (odds ratio: 1.44 (0.75-2.78)) or the older group (odds ratio: 0.92 (0.67
      1.26)). CONCLUSIONS: There was an inverse association between adult coeliac
      disease and cigarette smoking which was accounted for by middle-aged coeliacs
      having never smoked. These results are consistent with an age-dependent
      interaction between cigarette smoking and the other environmental factors
      implicated in coeliac disease, including gluten.

PMID- 12229977
TI  - Internal hernia presenting as obstructive jaundice and acute pancreatitis.
AB  - We report the first case of obstructive jaundice and acute pancreatitis caused by
      herniation of the small bowel through the foramen of Winslow in a 45-year-old
      man. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI)
      revealed dilated small-bowel loops positioned in the gastrohepatic space,
      dilatation of the gallbladder and both intrahepatic bile ducts, and mild swelling
      of the pancreas. A small-bowel series revealed a cluster of small-bowel loops in
      the mid-upper abdomen, with displacement of the stomach to the left. At
      laparotomy, there was an internal herniation of jejunal loop through the defect
      of gastrocolic ligament into the lesser sac and finally passing through the
      foramen of Winslow. The common bile duct was compressed externally by the
      herniated bowel and the pancreas was mildly swollen. To the best of our
      knowledge, these complications of internal hernia have not been reported
      previously.

PMID- 12229978
TI  - Determinants of bone loss in inflammatory bowel disease: a new role for
      interleukin-6 polymorphisms?

PMID- 12229979
TI  - High prevalence of hemochromatosis in Nord-Trondelag.

PMID- 12229980
TI  - Eosinophilic gastroenteritis.

PMID- 12229981
TI  - Self-expandable metallic stents with an anti-reflux mechanism for malignant
      strictures of gastroesophageal junction.

PMID- 12229982
TI  - Statistical inference for familial disease clusters.
AB  - In many epidemiologic studies, the first indication of an environmental or
      genetic contribution to the disease is the way in which the diseased cases
      cluster within the same family units. The concept of clustering is contrasted
      with incidence. We assume that all individuals are exchangeable except for their
      disease status. This assumption is used to provide an exact test of the initial
      hypothesis of no familial link with the disease, conditional on the number of
      diseased cases and the distribution of the sizes of the various family units. New
      parametric generalizations of binomial sampling models are described to provide
      measures of the effect size of the disease clustering. We consider models and an
      example that takes covariates into account. Ascertainment bias is described and
      the appropriate sampling distribution is demonstrated. Four numerical examples
      with real data illustrate these methods.

PMID- 12229983
TI  - Disease mapping of stage-specific cancer incidence data.
AB  - We propose two approaches for the spatial analysis of cancer incidence data with
      additional information on the stage of the disease at time of diagnosis. The two
      formulations are extensions of commonly used models for multicategorical response
      data on an ordinal scale. We include spatial and age-group effects in both
      formulations, which we estimate in a nonparametric smooth way. More specifically,
      we adopt a fully Bayesian approach based on Gaussian pairwise difference priors
      where additional smoothing parameters are treated as unknown as well. We argue
      that the methods are useful in monitoring the effectiveness of mass cancer
      screening and illustrate this through an application to data on cervical cancer
      in the former German Democratic Republic. The results suggest that there are
      large spatial differences in the stage proportions, which indicate spatial
      variability with respect to the introduction and effectiveness of Pap smear
      screening programs.

PMID- 12229984
TI  - Analysis of survival data from case-control family studies.
AB  - In case-control family studies with survival endpoint, age of onset of diseases
      can be used to assess the familial aggregation of the disease and the
      relationship between the disease and genetic or environmental risk factors.
      Because of the retrospective nature of the case--control study, methods for
      analyzing prospectively collected correlated failure time data do not apply
      directly. In this article, we propose a semiparametric quasi-partial-likelihood
      approach to simultaneously estimate the effect of covariates on the age of onset
      and the association of ages of onset among family members that does not require
      specification of the baseline marginal distribution. We conducted a simulation
      study to evaluate the performance of the proposed approach and compare it with
      the existing semiparametric ones. Simulation results demonstrate that the
      proposed approach has better performance in terms of consistency and efficiency.
      We illustrate the methodology using a subset of data from the Washington
      Ashkenazi Study.

PMID- 12229985
TI  - A frailty model for informative censoring.
AB  - To account for the correlation between failure and censoring, we propose a new
      frailty model for clustered data. In this model, the risk to be censored is
      affected by the risk of failure. This model allows flexibility in the direction
      and degree of dependence between failure and censoring. It includes the
      traditional frailty model as a special case. It allows censoring by some causes
      to be analyzed as informative while treating censoring by other causes as
      noninformative. It can also analyze data for competing risks. To fit the model,
      the EM algorithm is used with Markov chain Monte Carlo simulations in the E
      steps. Simulation studies and analysis of data for kidney disease patients are
      provided. Consequences of incorrectly assuming noninformative censoring are
      investigated.

PMID- 12229986
TI  - Use of quasi-least squares to adjust for two levels of correlation.
AB  - This article considers data with two levels of association. Our motivating
      example is an international intervention trial with repeated observations on
      subjects who reside within geographically defined clusters. To account for the
      potential correlation within clusters and within the repeated measurements that
      pertain to each subject, we apply a method based on generalized estimating
      equations for a correlation structure proposed by Lefkopoulou, Moore, and Ryan
      (1989, Journal of the American Statistical Association 84, 810-815).

PMID- 12229987
TI  - Estimating the number of species in a stochastic abundance model.
AB  - Consider a stochastic abundance model in which the species arrive in the sample
      according to independent Poisson processes, where the abundance parameters of the
      processes follow a gamma distribution. We propose a new estimator of the number
      of species for this model. The estimator takes the form of the number of
      duplicated species (i.e., species represented by two or more individuals) divided
      by an estimated duplication fraction. The duplication fraction is estimated from
      all frequencies including singleton information. The new estimator is closely
      related to the sample coverage estimator presented by Chao and Lee (1992, Journal
      of the American Statistical Association 87, 210-217). We illustrate the procedure
      using the Malayan butterfly data discussed by Fisher, Corbet, and Williams (1943,
      Journal of Animal Ecology 12, 42-58) and a 1989 Christmas Bird Count dataset
      collected in Florida, U.S.A. Simulation studies show that this estimator compares
      well with maximum likelihood estimators (i.e., empirical Bayes estimators from
      the Bayesian viewpoint) for which an iterative numerical procedure is needed and
      may be infeasible.

PMID- 12229988
TI  - Integrating mark-recapture-recovery and census data to estimate animal abundance
      and demographic parameters.
AB  - In studies of wild animals, one frequently encounters both census and mark
      recapture-recovery data. We show how a state-space model for census data in
      combination with the usual multinomial-based models for ring-recovery data
      provide estimates of productivity not available from either type of data alone.
      The approach is illustrated on two British bird species. For the lapwing, we
      calibrate how its recent decline could be due to a decrease in productivity. For
      the heron, there is no evidence for a decline in productivity, and the combined
      analysis increases significantly the strength of logistic regressions of survival
      on winter severity.

PMID- 12229989
TI  - Sample-size redetermination for repeated measures studies.
AB  - Clinical trialists recently have shown interest in two-stage procedures for
      updating the sample-size calculation at an interim point in a trial. Because many
      clinical trials involve repeated measures designs, it is desirable to have
      available practical two-stage procedures for such designs. Shih and Gould (1995,
      Statistics in Medicine 14, 2239-2248) discuss sample-size redetermination for
      repeated measures studies but under a highly simplified setup. We develop two
      stage procedures under the general mixed linear model, allowing for dropouts and
      missed visits. We present a range of procedures and compare their Type I error
      and power by simulation. We find that, in general, the achieved power is brought
      considerably closer to the required level without inflating the Type I error
      rate. We also derive an inflation factor that ensures the power requirement is
      more closely met.

PMID- 12229990
TI  - Adaptive decision making in a lymphocyte infusion trial.
AB  - We describe an adaptive Bayesian design for a clinical trial of an experimental
      treatment for patients with hematologic malignancies who initially received an
      allogeneic bone marrow transplant but subsequently suffered a disease recurrence.
      Treatment consists of up to two courses of targeted immunotherapy followed by
      allogeneic donor lymphocyte infusion. The immunotherapy is a necessary precursor
      to the lymphocyte infusion, but it may cause severe liver toxicity and is certain
      to cause a low white blood cell count and low platelets. The primary scientific
      goal is to determine the infusion time that has the highest probability of
      treatment success, defined as the event that the patient does not suffer severe
      toxicity and is alive with recovered white blood cell count 50 days from the
      start of therapy. The method is based on a parametric model accounting for
      toxicity, time to white blood cell recovery, and survival time. The design
      includes an algorithm for between-patient immunotherapy dose de-escalation based
      on the toxicity data and an adaptive randomization among five possible infusion
      times according to their most recent posterior success probabilities. A
      simulation study shows that the design reliably selects the best infusion time
      while randomizing greater proportions of patients to superior infusion times.

PMID- 12229991
TI  - Group sequential methods for an ordinal logistic random-effects model under
      misspecification.
AB  - Interim analyses in clinical trials are planned for ethical as well as economic
      reasons. General results have been published in the literature that allow the use
      of standard group sequential methodology if one uses an efficient test statistic,
      e.g., when Wald-type statistics are used in random-effects models for ordinal
      longitudinal data. These models often assume that the random effects are normally
      distributed. However, this is not always the case. We will show that, when the
      random-effects distribution is misspecified in ordinal regression models, the
      joint distribution of the test statistics over the different interim analyses is
      still a multivariate normal distribution, but a sandwich-type correction to the
      covariance matrix is needed in order to obtain the correct covariance matrix. The
      independent increment structure is also investigated. A bias in estimation will
      occur due to the misspecification. However, we will also show that the treatment
      effect estimate will be unbiased under the null hypothesis, thus maintaining the
      type I error. Extensive simulations based on a toenail dermatophyte onychomycosis
      trial are used to illustrate our results.

PMID- 12229992
TI  - Design of a binary biomarker study from the results of a pilot study.
AB  - Biomarkers are increasingly used in clinical and epidemiologic studies. Prior to
      these studies, small pilot studies are often conducted to assess the
      reproducibility of the biomarker. This article discusses how the results of a
      pilot study can be used to design subsequent studies when the biomarker is a
      binary assessment. We consider situations in which the pilot study has two
      factors (e.g., laboratory and individual) that are either crossed or nested. We
      discuss how binary random-effects models can be used for estimating the sources
      of variation and how parameter estimates from these models can be used to
      appropriately design future studies. We also show that fitting a linear variance
      components model that ignores the binary nature of the data is a simple
      alternative method that results in nearly unbiased and moderately efficient
      estimators of important design parameters. We illustrate the methodology with
      data from a study assessing the reproducibility of p53 immunohistochemistry in
      bladder tumors.

PMID- 12229993
TI  - Ranked set sampling for replicated sampling designs.
AB  - In practical ecological sampling studies, a certain design (such as plot sampling
      or line-intercept sampling) is usually replicated more than once. For each
      replication, the Horvitz-Thompson estimation of the objective parameter is
      considered. Finally, an overall estimator is achieved by averaging the single
      Horvitz-Thompson estimators. Because the design replications are drawn
      independently and under the same conditions, the overall estimator is simply the
      sample mean of the Horvitz-Thompson estimators under simple random sampling. This
      procedure may be wisely improved by using ranked set sampling. Hence, we propose
      the replicated protocol under ranked set sampling, which gives rise to a more
      accurate estimation than the replicated protocol under simple random sampling.

PMID- 12229994
TI  - A nonparametric Bayesian modeling approach for cytogenetic dosimetry.
AB  - In cytogenetic dosimetry, samples of cell cultures are exposed to a range of
      doses of a given agent. In each sample at each dose level, some measure of cell
      disability is recorded. The objective is to develop models that explain cell
      response to dose. Such models can be used to predict response at unobserved
      doses. More important, such models can provide inference for unknown exposure
      doses given the observed responses. Typically, cell disability is viewed as a
      Poisson count, but in the present work, a more appropriate response is a
      categorical classification. In the literature, modeling in this case is very
      limited. What exists is purely parametric. We propose a fully Bayesian
      nonparametric approach to this problem. We offer comparison with a parametric
      model through a simulation study and the analysis of a real dataset modeling
      blood cultures exposed to radiation where classification is with regard to number
      of micronuclei per cell.

PMID- 12229995
TI  - Estimation and inference for a spline-enhanced population pharmacokinetic model.
AB  - This article is motivated by an application where subjects were dosed three times
      with the same drug and the drug concentration profiles appeared to be the lowest
      after the third dose. One possible explanation is that the pharmacokinetic (PK)
      parameters vary over time. Therefore, we consider population PK models with time
      varying PK parameters. These time-varying PK parameters are modeled by natural
      cubic spline functions in the ordinary differential equations. Mean parameters,
      variance components, and smoothing parameters are jointly estimated by maximizing
      the double penalized log likelihood. Mean functions and their derivatives are
      obtained by the numerical solution of ordinary differential equations. The
      interpretation of PK parameters in the model and its flexibility are discussed.
      The proposed methods are illustrated by application to the data that motivated
      this article. The model's performance is evaluated through simulation.

PMID- 12229996
TI  - Small-sample inference for incomplete longitudinal data with truncation and
      censoring in tumor xenograft models.
AB  - In cancer drug development, demonstrating activity in xenograft models, where
      mice are grafted with human cancer cells, is an important step in bringing a
      promising compound to humans. A key outcome variable is the tumor volume measured
      in a given period of time for groups of mice given different doses of a single or
      combination anticancer regimen. However, a mouse may die before the end of a
      study or may be sacrificed when its tumor volume quadruples, and its tumor may be
      suppressed for some time and then grow back. Thus, incomplete repeated
      measurements arise. The incompleteness or missingness is also caused by drastic
      tumor shrinkage (<0.01 cm3) or random truncation. Because of the small sample
      sizes in these models, asymptotic inferences are usually not appropriate. We
      propose two parametric test procedures based on the EM algorithm and the Bayesian
      method to compare treatment effects among different groups while accounting for
      informative censoring. A real xenograft study on a new antitumor agent,
      temozolomide, combined with irinotecan is analyzed using the proposed methods.

PMID- 12229997
TI  - Parameter estimation in longitudinal studies with outcome-dependent follow-up.
AB  - In many observational studies, individuals are measured repeatedly over time,
      although not necessarily at a set of prespecified occasions. Instead, individuals
      may be measured at irregular intervals, with those having a history of poorer
      health outcomes being measured with somewhat greater frequency and regularity;
      i.e., those individuals with poorer health outcomes may have more frequent follow
      up measurements and the intervals between their repeated measurements may be
      shorter. In this article, we consider estimation of regression parameters in
      models for longitudinal data where the follow-up times are not fixed by design
      but can depend on previous outcomes. In particular, we focus on general linear
      models for longitudinal data where the repeated measures are assumed to have a
      multivariate Gaussian distribution. We consider assumptions regarding the follow
      up time process that result in the likelihood function separating into two
      components: one for the follow-up time process, the other for the outcome
      process. The practical implication of this separation is that the former process
      can be ignored when making likelihood-based inferences about the latter; i.e.,
      maximum likelihood (ML) estimation of the regression parameters relating the mean
      of the longitudinal outcomes to covariates does not require that a model for the
      distribution of follow-up times be specified. As a result, standard statistical
      software, e.g., SAS PROC MIXED (Littell et al., 1996, SAS System for Mixed
      Models), can be used to analyze the data. However, we also demonstrate that
      misspecification of the model for the covariance among the repeated measures
      will, in general, result in regression parameter estimates that are biased.
      Furthermore, results of a simulation study indicate that the potential bias due
      to misspecification of the covariance can be quite considerable in this setting.
      Finally, we illustrate these results using data from a longitudinal observational
      study (Lipshultz et al., 1995, New England Journal of Medicine 332, 1738-1743)
      that explored the cardiotoxic effects of doxorubicin chemotherapy for the
      treatment of acute lymphoblastic leukemia in children.

PMID- 12229998
TI  - A latent autoregressive model for longitudinal binary data subject to informative
      missingness.
AB  - Longitudinal clinical trials often collect long sequences of binary data. Our
      application is a recent clinical trial in opiate addicts that examined the effect
      of a new treatment on repeated binary urine tests to assess opiate use over an
      extended follow-up. The dataset had two sources of missingness: dropout and
      intermittent missing observations. The primary endpoint of the study was
      comparing the marginal probability of a positive urine test over follow-up across
      treatment arms. We present a latent autoregressive model for longitudinal binary
      data subject to informative missingness. In this model, a Gaussian autoregressive
      process is shared between the binary response and missing-data processes, thereby
      inducing informative missingness. Our approach extends the work of others who
      have developed models that link the various processes through a shared random
      effect but do not allow for autocorrelation. We discuss parameter estimation
      using Monte Carlo EM and demonstrate through simulations that incorporating
      within-subject autocorrelation through a latent autoregressive process can be
      very important when longitudinal binary data is subject to informative
      missingness. We illustrate our new methodology using the opiate clinical trial
      data.

PMID- 12229999
TI  - Median regression with censored cost data.
AB  - Because of the skewness of the distribution of medical costs, we consider
      modeling the median as well as other quantiles when establishing regression
      relationships to covariates. In many applications, the medical cost data are also
      right censored. In this article, we propose semiparametric procedures for
      estimating the parameters in median regression models based on weighted
      estimating equations when censoring is present. Numerical studies are conducted
      to show that our estimators perform well with small samples and the resulting
      inference is reliable in circumstances of practical importance. The methods are
      applied to a dataset for medical costs of patients with colorectal cancer.

PMID- 12230000
TI  - Accurate critical constants for the one-sided approximate likelihood ratio test
      of a normal mean vector when the covariance matrix is estimated.
AB  - Tang, Gnecco, and Geller (1989, Biometrika 76, 577-583) proposed an approximate
      likelihood ratio (ALR) test of the null hypothesis that a normal mean vector
      equals a null vector against the alternative that all of its components are
      nonnegative with at least one strictly positive. This test is useful for
      comparing a treatment group with a control group on multiple endpoints, and the
      data from the two groups are assumed to follow multivariate normal distributions
      with different mean vectors and a common covariance matrix (the homoscedastic
      case). Tang et al. derived the test statistic and its null distribution assuming
      a known covariance matrix. In practice, when the covariance matrix is estimated,
      the critical constants tabulated by Tang et al. result in a highly liberal test.
      To deal with this problem, we derive an accurate small-sample approximation to
      the null distribution of the ALR test statistic by using the moment matching
      method. The proposed approximation is then extended to the heteroscedastic case.
      The accuracy of both the approximations is verified by simulations. A real data
      example is given to illustrate the use of the approximations.

PMID- 12230001
TI  - Combining several screening tests: optimality of the risk score.
AB  - The development of biomarkers for cancer screening is an active area of research.
      While several biomarkers exist, none is sufficiently sensitive and specific on
      its own for population screening. It is likely that successful screening programs
      will require combinations of multiple markers. We consider how to combine
      multiple disease markers for optimal performance of a screening program. We show
      that the risk score, defined as the probability of disease given data on multiple
      markers, is the optimal function in the sense that the receiver operating
      characteristic (ROC) curve is maximized at every point. Arguments draw on the
      Neyman-Pearson lemma. This contrasts with the corresponding optimality result of
      classic decision theory, which is set in a Bayesian framework and is based on
      minimizing an expected loss function associated with decision errors. Ours is an
      optimality result defined from a strictly frequentist point of view and does not
      rely on the notion of associating costs with misclassifications. The implication
      for data analysis is that binary regression methods can be used to yield
      appropriate relative weightings of different biomarkers, at least in large
      samples. We propose some modifications to standard binary regression methods for
      application to the disease screening problem. A flexible biologically motivated
      simulation model for cancer biomarkers is presented and we evaluate our methods
      by application to it. An application to real data concerning two ovarian cancer
      biomarkers is also presented. Our results are equally relevant to the more
      general medical diagnostic testing problem, where results of multiple tests or
      predictors are combined to yield a composite diagnostic test. Moreover, our
      methods justify the development of clinical prediction scores based on binary
      regression.

PMID- 12230002
TI  - Quantifying the change of melanoma incidence by Breslow thickness.
AB  - Melanoma incidence has increased throughout the world over the past 25 years. A
      surrogate for the severity of melanoma is the Breslow thickness of the lesions.
      Data on melanoma, including Breslow thickness, were collected in 1978-1980 and
      1988-1990 from the Tasmania Tumor Registry. We use a density ratio model to
      quantify the change of melanoma by Breslow thickness. In this model, the ratio of
      two densities is assumed to have a known form up to a parameter, but the
      underlying densities are not modeled. This model includes the length bias
      sampling model as a special case. The Kolmogorov-Smirnov test statistic is used
      to test the correctness of the density ratio model. Model-based cumulative
      distribution estimation is studied. Methodology developed in this article is
      applied to the Tasmania Tumor Registry data.

PMID- 12230003
TI  - A simple technique to evaluate model sensitivity in the continual reassessment
      method.
AB  - The continual reassessment method (CRM) is a sequential design used in phase I
      cancer trials to determine the maximal dose with acceptable toxicity. It has been
      established that the CRM is consistent under model misspecification but not
      generally. When the method does not converge to the target percentile, some dose
      response models will be more sensitive than others in terms of how close the
      converged recommendation is to the target. In this article, we interpret the main
      condition under which the CRM is consistent and apply it to evaluate the
      sensitivity of the model used with the CRM. The technique presented is found to
      be a useful supplement to simulation when planning a phase I trial.

PMID- 12230004
TI  - Analysis of clustered and longitudinal binary data subject to response
      misclassification.
AB  - Misclassified clustered and longitudinal data arise in studies where the response
      indicates a condition identified through an imperfect diagnostic procedure.
      Examples include longitudinal studies that use an imperfect diagnostic test to
      assess whether or not an individual has been infected with a specific virus. This
      article presents methods to implement both population-averaged and cluster
      specific analyses of such data when the misclassification rates are known. The
      methods exploit the fact that the class of generalized linear models enjoys a
      closure property in the case of misclassified responses. Data from longitudinal
      studies of infectious disease will illustrate the findings.

PMID- 12230005
TI  - Estimating the variance of disease-prevalence estimates from population-based
      registries.
AB  - We propose a new Poisson method to estimate the variance for prevalence estimates
      obtained by the counting method described by Gail et al. (1999, Biometrics 55,
      1137-1144) and to construct a confidence interval for the prevalence. We evaluate
      both the Poisson procedure and the procedure based on the bootstrap proposed by
      Gail et al. in simulated samples generated by resampling real data. These studies
      show that both variance estimators usually perform well and yield coverages of
      confidence intervals at nominal levels. When the number of disease survivors is
      very small, however, confidence intervals based on the Poisson method have
      supranominal coverage, whereas those based on the procedure of Gail et al. tend
      to have below-nominal coverage. For these reasons, we recommend the Poisson
      method, which also reduces the computational burden considerably.

PMID- 12230006
TI  - A novel application of the multivariate power exponential distribution to
      repeated measurements from a crossover trial on insulin applied to rabbits.

PMID- 12230007
TI  - Effects of American ginseng berry extract on blood glucose levels in ob/ob mice.
AB  - In this study, we evaluated antihyperglycemic effects of American ginseng berry
      extract in diabetic ob/ob mice. Animals received daily intraperitoneal (IP)
      injections of the extract 150 mg/kg for 12 days. On days 5 and 12, the extract
      treated ob/ob mice had significantly lower fasting blood glucose levels compared
      to day 0 (both p < 0.05). Glucose tolerance improved significantly, which was
      shown by overall glucose excursion, calculated as area under the curve (AUC)
      during the two-hour IP glucose tolerance test. The AUC decreased by 31.8% on day
      12 compared to day 0 (p < 0.01). In addition, after 12 days of the berry extract
      treatment, a significant reduction in body weight (p < 0.01 compared to day 0)
      and a significant increase in body temperature (p < 0.01 compared to day 0) was
      noticeable. Our results support in vivo antihyperglycemic and antiobese activity
      of American ginseng berry extract that may prove to be of clinical importance in
      the prevention and treatment of Type 2 diabetes.

PMID- 12230008
TI  - Effects of bitter melon (Momordica charantia l.) or ginger rhizome (Zingiber
      offifinale rosc) on spontaneous mammary tumorigenesis in SHN mice.
AB  - The effects of chronic treatment with hot water extract of Bitter Melon
      (Momordica charantia L.) or Ginger Rhizome (Zingiber offifinale Rosc) on
      spontaneous mammary tumorigenesis were examined in SHN virgin mice. In mice given
      free access to extract of Bitter Melon (0.5%) or Ginger (0.125%) in drinking
      water, the development of mammary tumors was significantly inhibited.
      Furthermore, the former inhibited uterine adenomyosis with a common pathological
      background to mammary tumors and the latterinhibited mammary tumor growth. While
      the mechanism of the effects of these natural products remains to be clarified,
      there were no adverse effects of chronic treatment with these agents as estimated
      from body weight, food and water intake and various plasma component levels as
      well as external appearance. Thus, these natural products, popular in Japan as
      foodstuffs, also appear to have a health benefit.

PMID- 12230009
TI  - Effect of the aqueous extract of xiao-ban-xia-tang on gastric emptying in mice.
AB  - Gastric emptying effect of the aqueous extract of xiao-ban-xia-tang (XBXT) was
      investigated in mice. Mice with food deprived for 18 hours were orally
      administered a certain amount of test meal (ca. 0.8 g) equaling 0.8 ml in volume.
      The percentage of 0.8 g test meal remaining in the stomach after 20 minutes was
      estimated. It was shown that XBXT significantly antagonized dopamine- (0.56
      mg/kg, i.p.), not atropine- (0.3 mg/kg, i.p.), induced gastric emptying
      inhibition. It also significantly restored metoclopramide-induced (8 mg/kg, p.o.)
      propulsion and potentiated methylneostigmine-induced (2 mg/kg, p.o.) gastric
      emptying enhancement. The aqueous extract of Pinellia ternata, but not that of
      Zingiber officinale showed an inhibitory activity on gastric emptying. The
      present results suggest that XBXT possesses a regulative effect on gastric
      motility.

PMID- 12230010
TI  - Effect of ninjin-youei-to on Th1/Th2 type cytokine production in different mouse
      strains.
AB  - Ninjin-youei-to (NYT; ren-shen-yang-rong-tang in Chinese) is a traditional herbal
      formula, which is widely used in Japan, Korea and China to modulate physiological
      immunity. The effects of oral administration of NYT on cytokine production from
      splenocytes were investigated in both C57BL/6 and BALB/c mice in which Th1 and
      Th2 were dominant, respectively. Splenocytes from C57BL/6 and BALB/c mice, which
      took NYT orally forfour weeks, were cultured with anti-mouse CD3 mAb, and the
      supernatant was examined for cytokine production using enzyme-linked
      immunosorbent assay (ELISA). Administration of NYT to C57BL/6 mice, increased the
      production of interleukin-4 (IL-4) significantly, and slightly decreased
      interferon-y (IFN-gamma) production from splenocytes. In contrast, the same
      treatment significantly increased IFN-gamma secretion from splenocytes of BALB/c
      mice. No remarkable changes of IL-12 production from splenocytes were observed in
      either strain of mice. These results suggest that oral administration of NYT
      ameliorates the excessive inclination of Th1 and Th2 type cytokine production,
      and NYT may provide a beneficial effects for the treatment of diseases caused by
      a skewed Th1-Th2 balance in the immune system.

PMID- 12230011
TI  - Anti-inflammatory and hepatoprotective activity of peh-hue-juwa-chi-cao in male
      rats.
AB  - Peh-hue-juwa-chi-cao (PHJCC) is a common commercial name for the herbal extract
      of either Hedyotis diffusa (HD), H. corymbosa (HC), or Mollugo pentaphylla (MP).
      The present study was carried out to investigate the anti-inflammatory and
      hepatoprotective effects of these three extracts in rats. The results indicated
      that extracts of HC, HD and MP possess anti-inflammatory activity, and that MP
      has the greatest inhibition against carrageenan-induced paw edema. In the
      hepatoprotective study, results indicated that the three plant extracts
      significantly reduced the acute elevation of serum glutamate oxalate transaminase
      (sGOT) and serum glutamate pyruvate transaminase (sGPT) concentration, and
      alleviated the degree of liver damage 24 hours after the intraperitoneal
      administration of hepatotoxins.

PMID- 12230012
TI  - Ameliorative effect of Silene aprica on liver injuries induced by carbon
      tetrachloride and acetaminophen.
AB  - The effect of oral administration of a 50% ethanol extract of Silene aprica (SA)
      on acute liver injury was examined in rats intoxicated with carbon tetrachloride
      (CCl4) and acetaminophen. The results indicated that SA protected the liver from
      CCl4- and acetaminophen-induced injury as judged by morphological and biochemical
      observations. An increase in both lipid peroxidation (LPO) and triglyceride
      concentrations occurred in the liver with CCl4 injection, SA administration
      significantly reduced these changes.

PMID- 12230013
TI  - Cytoprotection by propolis ethanol extract of acute absolute ethanol-induced
      gastric mucosal lesions.
AB  - Acute p.o. administration of absolute ethanol (1.0 ml/kg) to fasted rats produced
      extensive necrosis of gastric mucosa. Pretreatment with p.o. administration of
      propolis ethanol extract (PEE) could effectively and dose-dependently prevent
      such necrosis. This protective effect is called "cytoprotection. "The maximal
      cytoprotective effect against absolute ethanol (AE)-induced gastric mucosal
      lesion was observed 1 hour after PEE administration. A gross examination of the
      gastric mucosa showed a marked improvement in groups receiving PEE. In order to
      further investigate the gastric protective mechanism of PEE, lipid peroxidation
      (LPO) levels in vivo and in vitro were estimated. PEE exhibited dose-dependent
      superoxide scavenging activity and antioxidant effects on AE-induced LPO in rat
      gastric mucosal homogenates. It was concluded that the gastric protective
      mechanism of PEE was due, at least in part, to its ability to inhibit LPO, and
      hence indirectly protect the gastric mucosa from oxidative stress.

PMID- 12230014
TI  - Toxicity of Nerium oleander and Rhazya stricta in Najdi sheep: hematologic and
      clinicopathologic alterations.
AB  - The toxic effects of oral administration of 0.25 g/kg Nerium oleander leaves,
      0.25 g/kg Rhazya stricta leaves or their mixture at 0.25 g/kg N. oleander leaves
      plus 0.25 g/kg R. stricta leaves on Najdi sheep were investigated. Daily oral
      dosing of R. stricta leaves for 42 days was not fatal to sheep while single oral
      doses of either N. oleander leaves or the mixture with R. stricta leaves proved
      fatal to animals within 24 hours with dyspnea, grunting, salivation, grinding of
      the teeth, ruminal bloat, frequent urination, ataxia and recumbency prior to
      death. The main lesions were widespread congestion or hemorrhage, pulmonary
      cyanosis, emphysema, bronchotracheal froths, and hepatonephropathy. The clinical
      and pathological changes were correlated with alterations in serum LDH and AST
      activities and concentrations of cholesterol, bilirubin, urea, total protein,
      albumin, and globulin and hematological values.

PMID- 12230015
TI  - The male silkworm moth (Antheraea pernyi) is a key ingredient in hu-bao and sheng
      bao for specific prolongation of the life-span of the male fruit fly (Drosophila
      melanogaster).
AB  - It is well established in Traditional Chinese Medicine that certain natural
      products, such as male silkworm moths, have different therapeutic effects on men
      than on women. These natural products have been used as dietary supplements
      specifically formulated for men or for women. However, this presumed sex-specific
      effect of certain natural products has not yet been confirmed experimentally with
      animal models or in human clinical trials. Here, using the fruit fly (Drosophila
      melanogaster) as a longevity model, we examined the effect of hu-bao (HB) and
      seng-bao (SB), two marketed health products made from a mixture of natural
      ingredients. Our results convincingly demonstrate that the effect of HB and SB
      are indeed specific for the male fly. The life-span of the male was significantly
      increased when HB or SB was added to the culture medium. In contrast, neither HB
      nor SB had much effect on the female fly. Upon removal of the male silkworm moth
      ingredient from HB or SB, the life-span prolongation effect of HB and SB was
      drastically diminished. Only with the addition of the male silkworm moth did the
      culture medium show a statistically significant life-span prolongation effect.
      This result suggests that the male silkworm moth is a key ingredient, in
      combination with other components, for specific prolongation of the life-span of
      male flies.

PMID- 12230016
TI  - The effect of Chinese medicine on bone cell activities.
AB  - In this experiment, we investigate the biochemical effects of traditional Chinese
      medicines via an in vitro bone cell culture. Ten different Chinese medicines were
      used in this study. The rat osteoblast-osteoclast co-culture system was used as
      the experimental model. After the cells grew to 80% confluence, various tested
      materials were added. The mitochondria activity of the bone cells after exposure
      to various preparations of Chinese medicines was determined by colorimetric
      assay. Biochemical markers such as protein content, lactate dehydrogenase (LDH),
      alkaline phosphatase (ALP), and acid phosphatase (ACP) titer were analyzed to
      evaluate the bone cell activity. When cultured with various Chinese medicines for
      24 hours, only four of these ten Chinese medicines had potential beneficial
      effects on the bone cell culture; and only Drynaria fortunei (Kunze) J. Sm. had a
      universal beneficial effect on bone cell metabolism. The major beneficial effect
      of Drynaria fortunei (Kunze) J. Sm. on bone cells is probably mediated by the
      induction of apoptosis of the osteoclast cell population. Continued study of
      alterations in gene expression of bone cells caused by Chinese medicines will
      improve our understanding of bone cell responses to various pharmacological
      interventions.

PMID- 12230017
TI  - Chinese medicine induces neurite outgrowth in PC12 mutant cells incapable of
      differentiation.
AB  - During continuous culture of neural PC12 cells, we obtained a drug-hypersensitive
      PC12 mutant cell that showed high stimulation of neurite outgrowth by various
      drugs. When several Chinese medicines such as shu-jing-huo-xie-tang and Wu-Ling
      San were provided to these PC12 mutant cells, the frequency of nerve growth
      factor (NGF)-induced neurite outgrowth increased approximately 30-fold compared
      to NGF alone. Neurite outgrowth induced by NGF in PC12 cells is accompanied by
      sustained activation of mitogen-activated protein kinase (MAPK); however, these
      Chinese medicines did not induce MAPK activity. The findings thus indicate that
      certain Chinese medicines may induce neurite outgrowth by a novel mechanism which
      is distinct from the NGF-activated pathway in PC12 mutant cells.

PMID- 12230018
TI  - Effects of Inula Britannica on the production of antibodies and cytokines and on
      T cell differentiation in C57BL/6 mice immunized by ovalbumin.
AB  - In this study, we investigated the effects of Inula Britannica on the production
      of antibodies against ovalbumin, and the differentiation of T cells, in C57BL/6
      mice. The oral administration of Inula Britannica suppressed IL-4 and IL-6
      production in lymphocytes collected from an inguinal lymph node in the immunized
      leg. On the other hand, the intraperitoneal administration of Inula Britannica
      suppressed IgG1 production, the ratio of IFN-gamma+IL-4-/IFN-gamma-IL-4+ cells
      and cytokine production of IL-6. It was presumed that the effects of Inula
      Britannica on the production of antibodies were induced by regulation of the
      balance of Th1 and Th2. Further, IL-4 and IL-6 production by lymphocytes
      collected from an inguinal lymph node in the immunized leg were suppressed, and
      therefore production of antibodies was suppressed.

PMID- 12230019
TI  - Extract from the leaves of Toona sinensis roemor exerts potent antiproliferative
      effect on human lung cancer cells.
AB  - Recent study indicated that the components of Toona sinensis Roemor have potent
      anti-inflammatory and analgesic effects. These components have also been reported
      to inhibit the growth of boils in vivo. In this study, we investigated the effect
      of crude extract from the leaves of Toona sinensis Roemor on the proliferation of
      A549 lung cancer cells. We found that the extract effectively blocked cell cycle
      progression by inhibiting the expression of cyclin D1 and E in A549 cells.
      Additionally, incubation of the extract led to activation of caspase-3-like
      proteases and apoptotic cell death. Conversely, the extract did not show any
      significant cytotoxic effect on primarily cultured human foreskin fibroblasts or
      MRC-5 human lung fibroblasts. Therefore, antiproliferative action of the extract
      is specific for tumor cells. Our results suggest that the components of Toona
      sinensis Roemor have potent anticancer effects in vitro and identification of the
      useful components in the extract may lead to the development of a novel class of
      anticancer drugs.

PMID- 12230020
TI  - Effects of garlic components diallyl sulfide and diallyl disulfide on arylamine N
      acetyltransferase activity and 2-aminofluorene-DNA adducts in human promyelocytic
      leukemia cells.
AB  - Two components of garlic, diallyl sulfide (DAS) and diallyl disulfide (DADS),
      inhibited arylamine N-acetyltransferase (NAT) activity and 2-aminofluorene-DNA
      adduct in human promyelocytic leukemia cells (HL-60). The NAT activity was
      measured by high performance liquid chromatography assaying for amounts of N
      acetyl-2-aminofluorene (2-AAF) and remaining 2-aminofluorene (2-AF). Cellular
      cytosols and intact cell suspensions were assayed. The inhibition of NAT activity
      and 2-AF-DNA adduct formation in human leukemia cells by DAS and DADS were dose
      dependent and were directly proportional. The data also indicated that DAS and
      DADS decrease the apparent values of Km and Vmax from human leukemia cells in
      both assays. This is the first report of garlic components affecting human
      leukemia cell NAT activity and 2-AF-DNA adduct formation.

PMID- 12230021
TI  - The improvement of luteal insufficiency in fecund women by tokishakuyakusan
      treatment.
AB  - The effect of tokishakuyakusan, a Chinese herbal medicine, was examined, in vivo,
      in women with luteal insufficiency and in women with normal menstrual cycles.
      Luteal insufficiency was determined by daily measurement of basal body
      temperature and plasma progesterone levels. Tokishakuyakusan improved luteal
      insufficiency. Furthermore, the effects of tokishakuyakusan on prolactin,
      gonadotropins, steroids, angiotensin II, ANP and renin levels in the blood of
      women with normal menstrual cycles were studied, as were the medicine's effects
      on estrogens, pregnenediol and LH in the urine of the same women.
      Tokishakuyakusan had no adverse effect on hormonal levels in either blood or
      urine. Furthermore, no clinical side effects were detected. These results suggest
      that tokishakuyakusan improves luteal insufficiency in women but does not affect
      the hormonal levels of women with normal menstrual cycles.

PMID- 12230022
TI  - Antioxidant and anticonvulsant effect of a modified formula of chaihu-longu-muli
      tang.
AB  - Antiepileptic drug therapy in individuals with epilepsy can induce free radical
      generation and profound lipid peroxidation. Some Chinese herbs with antiepileptic
      potential show antioxidant effects. We performed an open add-on study of TW970, a
      modified formula of the Chinese medicine "chaihu-longu-muli-tang", on 20 patients
      with refractory epilepsy and a seizure frequency of at least four fits per month,
      and another 20 patients with benign epilepsy and a seizure frequency of less than
      four fits per month. The control group consisted of 20 age-matched healthy
      adults. Seizure frequency, serum malondialdehyde (MDA), glutathione (GSH) and
      copper-zinc superoxide dismutase (Cu,Zn-SOD) were investigated in patients with
      refractory and benign epilepsy before and after four months add-on treatment of
      TW970. There was a decrease in seizure frequency in refractory epileptics from
      13.4 +/- 3.4 to 10.7 +/- 2.5/per month, although the p value was 0.084. Before
      TW970 add-on treatment, a significant enhancement of lipid peroxidation with
      increased MDA and Cu,Zn-SOD activities together with decreased GSH were seen in
      refractory epileptics compared with normal controls. After TW970 add-on treatment
      of refractory epileptics for four months, normalization of MDA and Cu,Zn-SOD
      levels was achieved. Before and after TW970 add-on treatment, there were no
      statistically significant changes of the above-mentioned parameters in the
      patients with benign epilepsy. These results suggest that TW970 can reduce the
      seizure frequency in patients with refractory epilepsy and this may be due to the
      antioxidant effects of the modified formula of chaihu-longu-muli-tang.

PMID- 12230023
TI  - Effects of kakkon-to and sairei-to on aqueous flare elevation after complicated
      cataract surgery.
AB  - We evaluate prospectively the effects of traditional herbal medicines on
      elevation of aqueous flare after complicated cataract surgery. Twenty-seven
      patients with bilateral complicated cataract undergoing phacoemulsification with
      intraocular lens implantation were studied. The patients received no herbal
      medicine when the right eyes underwent cataract surgery. Fifteen patients were
      given kakkon-to (ge-gen-yang in Chinese) granules (7.5 g daily) and 12 patients
      were given sairei-to (cai-ling-tang in Chinese) granules (9.0 g daily), for 3
      days before surgery, the day of surgery, and for 7 days after surgery when the
      left eyes underwent cataract surgery. Diclofenac eyedrops were instilled in all
      patients. Aqueous flare was measured before and after surgery. The differences in
      preoperative flare intensities between groups treated with Kakkon-to and Sairei
      to were not significant. In the untreated right eyes of the kakkon-to and Sairei
      to groups, the flare was 99.1 and 89.6 photon counts/msec, respectively, on day
      1, and then gradually decreased. The flare intensities on days 1, 3, and 5 in the
      kakkon-to treated left eyes were significantly lower than in those of the
      untreated right eyes (Fig. 1). The flare intensities in the Sairei-to treated
      left eyes were the same as those in the untreated right eyes. Kakkon-to
      contributed to a reduction of aqueous flare elevation after surgery for
      complicated cataract.

PMID- 12230024
TI  - The efficacy of herbal medicine (kampo) in reducing the adverse effects of IFN
      beta in chronic hepatitis C.
AB  - The purpose of this study was to determine if the adverse effects of interferon
      (IFN) in hepatitis C patients could be reduced by treatment with Japanese
      Oriental (Kampo) medicine. Twelve patients with chronic hepatitis C were treated
      with a combination of IFN-beta and either Mao-to or Dai-seiryu-to (groups A and
      B), and 16 patients were treated with IFN-beta alone (group C). Mao-to was
      administered to eight patients and Dai-seiryu-to was administered to four in
      groups A and B, respectively. Adverse effects were evaluated by clinical and
      laboratory examinations. The severity of symptoms was daily self-classified into
      four categories (1: none, 2: very slight, 3: moderate, and 4: serious), using a
      questionnaire consisting of 29 items. Scores of symptom such as discomfort and
      fever in group A, and discomfort, general malaise, paresthesia and arthralgia in
      group B were significantly lower than those in group C (p < 0.05). In all
      patients, HCV-RNA was negative at the end of the treatment, and serum alanine
      aminotransferase (ALT) levels had normalized transiently in all group A and B
      patients with genotype 1b by 2 weeks after cessation of IFN treatment. This study
      indicates that Kampo medicines are useful for reducing the adverse effects
      accompanying IFN treatment in patients with chronic hepatitis C without reducing
      the antiviral effects.

PMID- 12230025
TI  - The physiological mechanisms of 2 Hz electroacupuncture: a study using blink and
      H reflex.
AB  - Our previous studies have shown that the cerebral cortex modulates the
      physiological mechanisms of acupuncture. However, the role of the brain stem and
      spinal cord in acupuncture remains unclear. The present study investigated the
      action of the brain stem and spinal cord in acupuncture. A total of eight healthy
      adult volunteers were studied. Electrical stimulation of the supraorbital nerve
      in the supraorbital foramen was used to evoke the blink reflex. Electrical
      stimulation of the posterior tibial nerve in the right popliteal fossa was used
      to evoke the H reflex. Electroacupuncture (EA) of 2 Hz was applied to the Zusanli
      acupoint in the right or left leg. The area of the R1 and R2 components of the
      blink reflex, and the greatest H/M ratio and H-M interval of the H reflex were
      measured before EA, during EA and at various post-EA periods. These data were
      analyzed quantitatively by a computerized electromyographic examination system.
      The results indicate that EA did not change the R1 and ipsilateral R2 components
      of the blink reflex. EA depressed the contralateral R2 component of the blink
      reflex 10 minutes and 40 minutes after the start of EA, but not after 5 minutes.
      EA applied to the Zusanli acupoint did not change the H/M ratio or the H-M
      interval of the H reflex. The results of this study indicate that 2 Hz EA of the
      Zusanli acupoint does not change the R1 component of the blink reflex, and the
      H/M ratio and the H-M interval of the H reflex, suggesting that 2 Hz EA does not
      change the monosynaptic reflex in the brain stem and spinal cord in humans. We
      also found that EA at 2 Hz depressed the contralateral but not the ipsilateral R2
      component of the blink reflex, suggesting that longer pathways, perhaps including
      the cerebral cortex, may play a role in the physiological mechanisms responsible
      for the effectiveness of acupuncture.

PMID- 12230026
TI  - Acupuncture stimulation of the vision-related acupoint (Bl-67) increases c-Fos
      expression in the visual cortex of binocularly deprived rat pups.
AB  - Our previous study with functional magnetic resonance imaging (MRI) demonstrated
      that acupuncture stimulation of the vision-related acupoint, B1-67, activates the
      visual cortex of the human brain. As a further study on the effect of B1-67
      acupuncture stimulation on the visual cortex, we examined c-Fos expression in
      binocularly deprived rat pups. Binocular deprivation significantly reduced the
      number of c-Fos-positive cells in the primary visual cortex, compared with that
      of normal control rat pups. Interestingly, acupuncture stimulation of B1-67
      resulted in a significant increase in the number of c-Fos-positive cells in the
      primary visual cortex, while acupuncture stimulation of other acupoints less
      important for visual function had no significant effect on c-Fos expression in
      the primary visual cortex. The results suggest the possibility of vision-related
      acupoint (B1-67) having an influence over the activity of the primary visual
      cortex.

PMID- 12230027
TI  - The effect of acupuncture on the coronary arteries as evaluated by coronary
      angiography: a preliminary report.
AB  - The Neiguan acupuncture point (EH-6) of the heart meridian is often used for
      circulatory disorders. To clarify this effect, we measured coronary diameters in
      patients with angina pectoris following acupuncture stimulation using
      cardioangiography. Two kinds of acupuncture stimulation, the leaving needle (LN)
      and the sparrow pecking method (SPM), were employed for this study. No
      significant differences were found between LN and SPM. Concerning the pattern of
      coronary reaction, coronary constriction following acupuncture showed a
      relationship to patients with vasospastic angina. Coronary dilation following
      acupuncture showed a relationship to patients with Syndrome X. The mean
      dilatation with acupuncture was 68.8% of that caused by isosorbide dinitrate.
      These findings may help to clarify the mechanism of acupuncture treatment.

PMID- 12230028
TI  - Aquapuncture therapy of repeat breeding in dairy cattle.
AB  - Repeat breeders cause great economic loss in dairy herds. This study determined
      the efficacy of simple aquapuncture therapy (acupuncture combined with injection)
      to treat repeat breeders in two dairy herds (one in Hsinchu County and the other
      in Tainan County). Both herds had used gonadotropin-releasing hormone (GnRH)
      beforehand to treat the symptom but the success rate was poor--about 30%.
      Therefore, cows that failed to respond to GnRH were given the aquapuncture
      treatment. A total of 18 animals (two heifers and 16 cows) that had failed to
      conceive to 3-9 services were treated by aquapuncture, in which 10 ml and 5 ml of
      50% glucose solution were injected at Baihui (Hundred Meetings, the depression in
      the center of the lumbosacral space) and Shenpeng (Kidney Shelf, the depression
      in the space between the lumbar vertebral transverse processes 5-6) acupoints,
      respectively with a 21G, 1.5-inch hypodermic needle. Both acupoints belong to the
      traditional acupuncture points of bovine and equine systems. Most animals showed
      heat within 14 days after aquapuncture and were inseminated artificially. Serum
      progesterone concentrations and rectal palpation were used for pregnancy
      diagnosis. The pregnancy rate after the treatment was 14/18 (77.7%) and 12/18
      (66.6%) based on progesterone concentration and rectal palpation respectively,
      suggesting acupuncture as a simple and effective method to treat repeat breeders
      in dairy herds. However, the final result obtained from actual delivery of fetus
      in the experimental animals was only 8/18 (44.4%).

PMID- 12230029
TI  - Changes in EEG of children during brain respiration-training.
AB  - Brain Respiration (BR)-training is a unique form of breathing exercise that
      develops potential ability by facilitating brain function. It is recognized as an
      effective method of improving the scholastic aptitude and emotional stability of
      children. The present study was designed to investigate the characteristics of
      the EEG during this training. Spectral analysis was used to examine the relative
      power in the EEG of 12 children while they practiced BR-training, and these were
      compared to those of 12 matched controls. BR-trainees showed a lower theta rhythm
      than the controls before the training session began and lower beta2 power before,
      during and after the session. In contrast, the BR subjects showed greater
      relative alpha1 power than the controls in the left frontal region during BR
      training, which persisted throughout the BR-training schedule. There is evidence
      that decreased theta and beta waves may be correlated with emotional maturation,
      whilst increased alpha waves are associated with educational achievement. These
      findings enhance our understanding of the neurophysiological basis of the effects
      of BR-training upon emotion and maturation.

PMID- 12230030
TI  - What's in a name? A systematic review of the nomenclature of Chinese medical
      formulae.
AB  - Traditional Chinese Medicine (TCM) has been modified to some extent in other Far
      Eastern countries such as Korea and Japan. Researchers of each of the three
      countries seem to use different English names for the same Chinese medicinal
      formulae. Lack of knowledge of the Chinese characters is destined to increase
      this confusion. In order to investigate this matter systematically, all
      investigations of Chinese medicine formulae published in the American Journal of
      Chinese Medicine (AJCM, 1997-March 2001) were evaluated. Moreover, PubMed (1966
      June 2001) was searched using keywords differentiated by language, location and
      number of hyphens, and upper-or lower-case of the first letter of the English
      equivalent of each Chinese character. Fifty-four formulae of TCM were identified
      in 45 reports published in AJCM. Thirty-two were named in Chinese only (23
      reports); six in Japanese (six reports); and five in Korean (five reports). Ten
      formulae were named in Japanese with the Chinese name in brackets (ten reports);
      and one in Chinese with the Japanese name in brackets (one report). By
      computerized literature search, different numbers of research papers were
      retrieved by using keywords differentiated by language, location and number of
      hyphens. Such confusion may prevent progress in the evaluation of TCM. To
      increase the efficiency of studies on Chinese medical formulae, standardization
      of terminology is required.

PMID- 12230031
TI  - InterPro: an integrated documentation resource for protein families, domains and
      functional sites.
AB  - The exponential increase in the submission of nucleotide sequences to the
      nucleotide sequence database by genome sequencing centres has resulted in a need
      for rapid, automatic methods for classification of the resulting protein
      sequences. There are several signature and sequence cluster-based methods for
      protein classification, each resource having distinct areas of optimum
      application owing to the differences in the underlying analysis methods. In
      recognition of this, InterPro was developed as an integrated documentation
      resource for protein families, domains and functional sites, to rationalise the
      complementary efforts of the individual protein signature database projects. The
      member databases - PRINTS, PROSITE, Pfam, ProDom, SMART and TIGRFAMs - form the
      InterPro core. Related signatures from each member database are unified into
      single InterPro entries. Each InterPro entry includes a unique accession number,
      functional descriptions and literature references, and links are made back to the
      relevant member database(s). Release 4.0 of InterPro (November 2001) contains
      4,691 entries, representing 3,532 families, 1,068 domains, 74 repeats and 15
      sites of post-translational modification (PTMs) encoded by different regular
      expressions, profiles, fingerprints and hidden Markov models (HMMs). Each
      InterPro entry lists all the matches against SWISS-PROT and TrEMBL (2,141,621
      InterPro hits from 586,124 SWISS-PROT and TrEMBL protein sequences). The database
      is freely accessible for text- and sequence-based searches.

PMID- 12230032
TI  - HMM-based databases in InterPro.
AB  - Protein family databases are an important resource for protein annotation and
      understanding protein evolution and function. In recent years hidden Markov
      models (HMMs) have become one of the key technologies used for detection of
      members of these families. This paper reviews the Pfam, TIGRFAMs and SMART
      databases that use the profile-HMMs provided by the HMMER package.

PMID- 12230033
TI  - ProDom: automated clustering of homologous domains.
AB  - The ProDom database is a comprehensive set of protein domain families
      automatically generated from the SWISS-PROT and TrEMBL sequence databases. An
      associated database, ProDom-CG, has been derived as a restriction of ProDom to
      completely sequenced genomes. The ProDom construction method is based on
      iterative PSI-BLAST searches and multiple alignments are generated for each
      domain family. The ProDom web server provides the user with a set of tools to
      visualise multiple alignments, phylogenetic trees and domain architectures of
      proteins, as well as a BLAST-based server to analyse new sequences for homologous
      domains. The comprehensive nature of ProDom makes it particularly useful to help
      sustain the growth of InterPro.

PMID- 12230034
TI  - The PRINTS database: a resource for identification of protein families.
AB  - The PRINTS database houses a collection of protein fingerprints, which may be
      used to assign family and functional attributes to uncharacterised sequences,
      such as those currently emanating from the various genome-sequencing projects.
      The April 2002 release includes 1,700 family fingerprints, encoding approximately
      10,500 motifs, covering a range of globular and membrane proteins, modular
      polypeptides and so on. Fingerprints are groups of conserved motifs that, taken
      together, provide diagnostic protein family signatures. They derive much of their
      potency from the biological context afforded by matching motif neighbours; this
      makes them at once more flexible and powerful than single-motif approaches. The
      technique further departs from other pattern-matching methods by readily allowing
      the creation of fingerprints at superfamily-, family- and subfamily-specific
      levels, thereby allowing more fine-grained diagnoses. Here, we provide an
      overview of the method of protein fingerprinting and how the results of
      fingerprint analyses are used to build PRINTS and its relational cousin, PRINTS
      S.

PMID- 12230035
TI  - PROSITE: a documented database using patterns and profiles as motif descriptors.
AB  - Among the various databases dedicated to the identification of protein families
      and domains, PROSITE is the first one created and has continuously evolved since.
      PROSITE currently consists of a large collection of biologically meaningful
      motifs that are described as patterns or profiles, and linked to documentation
      briefly describing the protein family or domain they are designed to detect. The
      close relationship of PROSITE with the SWISS-PROT protein database allows the
      evaluation of the sensitivity and specificity of the PROSITE motifs and their
      periodic reviewing. In return, PROSITE is used to help annotate SWISS-PROT
      entries. The main characteristics and the techniques of family and domain
      identification used by PROSITE are reviewed in this paper.

PMID- 12230036
TI  - High-quality protein knowledge resource: SWISS-PROT and TrEMBL.
AB  - SWISS-PROT is a curated protein sequence database which strives to provide a high
      level of annotation (such as the description of the function of a protein, its
      domain structure, post-translational modifications, variants, etc.), a minimal
      level of redundancy and a high level of integration with other databases.
      Together with its automatically annotated supplement TrEMBL, it provides a
      comprehensive and high-quality view of the current state of knowledge about
      proteins. Ongoing developments include the further improvement of functional and
      automatic annotation in the databases including evidence attribution with
      particular emphasis on the human, archaeal and bacterial proteomes and the
      provision of additional resources such as the International Protein Index (IPI)
      and XML format of SWISS-PROT and TrEMBL to the user community.

PMID- 12230037
TI  - Applications of InterPro in protein annotation and genome analysis.
AB  - The applications of InterPro span a range of biologically important areas that
      includes automatic annotation of protein sequences and genome analysis. In
      automatic annotation of protein sequences InterPro has been utilised to provide
      reliable characterisation of sequences, identifying them as candidates for
      functional annotation. Rules based on the InterPro characterisation are stored
      and operated through a database called RuleBase. RuleBase is used as the main
      tool in the sequence database group at the EBI to apply automatic annotation to
      unknown sequences. The annotated sequences are stored and distributed in the
      TrEMBL protein sequence database. InterPro also provides a means to carry out
      statistical and comparative analyses of whole genomes. In the Proteome Analysis
      Database, InterPro analyses have been combined with other analyses based on
      CluSTr, the Gene Ontology (GO) and structural information on the proteins.

PMID- 12230038
TI  - The Bio* toolkits--a brief overview.
AB  - Bioinformatics research is often difficult to do with commercial software. The
      Open Source BioPerl, BioPython and Biojava projects provide toolkits with
      multiple functionality that make it easier to create customised pipelines or
      analysis. This review briefly compares the quirks of the underlying languages and
      the functionality, documentation, utility and relative advantages of the Bio
      counterparts, particularly from the point of view of the beginning biologist
      programmer.

PMID- 12230039
TI  - Multiple sequence alignment--the gateway to further analysis.

PMID- 12230040
TI  - Health care challenges created by substance abuse: the whole is definitely bigger
      than the sum of its parts.

PMID- 12230041
TI  - Perinatal care for women who are addicted: implications for empowerment.
AB  - This article explores societal responses to perinatal drug abuse, including
      stigmatic attitudes and behaviors of health care workers that are directed toward
      women who abuse drugs during pregnancy. Health care providers' stigmatic
      responses can deter women from receiving perinatal care and place women and their
      unborn children at risk. Because poor women and women of color face a greater
      probability of being prosecuted or losing custody of their children for using
      drugs while they are pregnant, the article emphasizes societal responses to these
      client populations. Empowering strategies are suggested by which social workers
      and clients can potentially redefine perinatal drug abuse as a health problem
      rather than a legal issue and improve the environment in which perinatal care is
      provided.

PMID- 12230042
TI  - Drug abuse risks for acculturating immigrant adolescents: case study of Asian
      Indians in the United States.
AB  - Immigrant parents and their U.S.-born children may experience stressful family
      conflicts over the disparate sociocultural norms of the United States and their
      country of origin. Such stresses may heighten adolescents' vulnerability to drug
      abuse. This article documents the extent of drug use in a sample of 200 U.S.-born
      Asian Indian adolescents. According to the study participants' self-reports on
      lifetime use, 28 percent had used alcohol on at least one occasion, 16.5 percent
      had used cigarettes, and 2.5 percent had used marijuana. Adolescents who placed
      importance on their parents' drug abuse prevention messages tended not to use
      drugs. The implications of the study's findings for drug abuse assessment,
      treatment, and prevention are discussed.

PMID- 12230043
TI  - College students' drinking: master's in social work compared with undergraduate
      students.
AB  - The article is based on the supposition that personal experiences with alcohol
      influence how master's of social work (MSW) students interact with problem
      drinking clients and their significant others. The study compared self-report
      drinking practices of 413 MSW students with 552 undergraduate college students
      from universities in the Northeast. The variables were having five or more drinks
      during the past two weeks, feeling the need to cut down, having an alcohol
      problem, recovering, and consuming the student's last drink. The MSW students,
      within age and gender categories, did not drink as excessively as the
      undergraduate students, although a greater percentage were recovering, a finding
      of high relevance for the training of these students.

PMID- 12230044
TI  - One last pleasure? Alcohol use among elderly people in nursing homes.
AB  - The study discussed in this article describes the alcohol-related policies,
      practices, and problems experienced by a sample of 111 intermediate care
      facilities and homes for elderly people. Data were collected using a semi
      structured telephone interview and indicate that alcohol use and associated
      problems among nursing home residents are common. Despite the problems reported,
      screening for alcohol problems among residents, treatment of identified problems,
      and training of staff were not found to be widespread. Ambiguity about the role
      of alcohol as a social beverage or as a psychoactive substance to be managed was
      identified. Challenges to social workers and social work education are
      identified.

PMID- 12230045
TI  - Families helping families: implementing a multifamily therapy group with
      substance-abusing adolescents.

PMID- 12230046
TI  - Brief motivational intervention for substance-abusing delinquent adolescents:
      guided self-change as a social work practice innovation.

PMID- 12230047
TI  - Structured stories: reinforcing social skills in rural substance abuse treatment.

PMID- 12230048
TI  - Treatment with lesbian alcoholics: healing shame and internalized homophobia for
      ongoing sobriety.

PMID- 12230049
TI  - Harm reduction and injection drug use: pragmatic lessons from a public health
      model.

PMID- 12230050
TI  - The Xchange point: a drop-in center for African American active injection drug
      users.

PMID- 12230051
TI  - A comparison of drug use between welfare-receiving arrestees and non-welfare
      receiving arrestees.

PMID- 12230052
TI  - Defining substance abusers using a prism: what you see is what you get.

PMID- 12230053
TI  - Social work and the art of substance abuse counseling.

PMID- 12230054
TI  - Substance abuse and elderly people.

PMID- 12230055
TI  - Early laparoscopy instruments.

PMID- 12230056
TI  - The benefits and problems associated with minimal access surgery.
AB  - The place of minimal access surgery (MAS) in current gynaecological practice
      remains controversial. As a consequence, MAS techniques have been subject to a
      significant amount of prospective, evidence-based assessment. The ultimate
      results of these comparative trials will undoubtedly have a profound impact on
      the future direction of our speciality. It is timely, therefore, to review the
      currently available data. Evidence from 2195 patients in 23 randomised clinical
      trials of five different treatment modalities (ectopic, ovarian cysts,
      myomectomy, colposuspension and hysterectomy) clearly demonstrates that
      uncomplicated MAS procedures produce patient friendly benefits, at least in the
      short term. No matter what operation is performed, the laparoscopic approach is
      associated with less pain, shorter hospital stay and shorter recovery. These
      immediate patient-orientated benefits are a generic consequence of replacing the
      manoeuvres of open surgery through laparotomy incisions with minimal access.
      These benefits must be offset against significant disadvantages. Minimal access
      surgery procedures always require the use of expensive, high technology equipment
      and usually take longer to perform. Such procedures may be more costly than
      current open procedures and costs will, in part, be dependent on the amount of
      disposable equipment employed. Patients undergoing MAS procedures may be at risk
      of new and/or increased risk of traditional complications. The longer-term
      results of most MAS procedures have not yet been determined. These potential
      benefits and disadvantages of MAS require that each procedure is carefully and
      individually assessed. This paper seeks to review the current evidence.

PMID- 12230057
TI  - Laparoscopic entry: a literature review and analysis of techniques and
      complications of primary port entry.
AB  - OBJECTIVE: To obtain consensus as to the optimal form of entry technique for
      access to the peritoneal cavity. DESIGN: A meta-analysis of all relevant English
      language studies of laparoscopic entry complications. MAIN OUTCOME MEASURES:
      Incidence of bowel and major vascular injuries. RESULTS: Bowel injuries occur in
      0.7/1,000 and major vascular injuries in 0.4/1,000. The overall incidence of
      major injuries at time of entry is 1.1/1,000. The direct entry technique is
      associated with a significantly reduced major injury incidence of 0.5/1,000, when
      compared to both open and Veress entry produces (1.1 and 0.9/1,000 respectively,
      p = 0.0005). Entry-related bowel injuries are reported more often following
      general surgical laparoscopies than with gynaecological procedures (p = 0.001).
      No such difference is seen in the incidence of vascular injuries (p = 0.987).
      Open entry is statistically more likely to be associated with bowel injury than
      either Veress needle or direct entry However, open entry appears to minimise
      vascular injury at time of entry. CONCLUSIONS: There remains no clear evidence as
      to the optimal form of laparoscopic entry in the low-risk patient. However,
      direct entry may be an under-utilised and safe alternative to the Veress needle
      and open entry technique.

PMID- 12230058
TI  - Fertility outcomes following laparoscopic tubal re-anastomosis post tubal
      sterilisation.
AB  - OBJECTIVE: To determine fertility outcomes following laparoscopic tubal re
      anastomosis. DESIGN: Retrospective mail follow-up. SETTING: Specialised private
      gynaecological endoscopy practice. POPULATION OR SAMPLE: 19 women who underwent
      laparoscopic tubal reanastomosis following tubal sterilisation. MAIN OUTCOME
      MEASURES: Pregnancy rate and 'take home baby' rate. RESULTS: 15 (78.9%) of women
      became pregnant, and 13 (68.4%) carried pregnancies to viability. The mean
      operating time was 115 minutes (range 90-200 minutes). The mean reversal to
      pregnancy interval was 8.3 months (1-24 months). CONCLUSIONS: This study suggests
      that the pregnancy and 'take home baby' rates after laparoscopic reversal of
      tubal sterilisation compare favourably with open microsurgical reversal and in
      vitro fertilisation.

PMID- 12230059
TI  - Changes in vesicourethral function following laparoscopic hysterectomy versus
      abdominal hysterectomy.
AB  - OBJECTIVE: To assess whether total hysterectomy is associated with increased
      postoperative vesicourethral abnormalities. SAMPLE: Forty-five patients had a
      laparoscopic hysterectomy and 36 patients had a total abdominal hysterectomy.
      DESIGN: Before and after hysterectomy, patients underwent a urinalysis, a
      personal interview, and an urodynamic study. RESULTS: Of the laparoscopic
      hysterectomy group, 27 patients (60%) exhibited urinary symptoms preoperatively,
      and 22 patients (48.9%) remained symptomatic following surgery. There was no
      significant change in the number of women with one or more urinary symptoms, but
      the incidence of urinary frequency and stress incontinence decreased
      significantly following hysterectomy (p < 0.05). Of the total abdominal
      hysterectomy group, preoperative voiding symptoms were present in 22 patients
      (61.1%). After surgery, urinary symptoms were present in 19 patients (52.8%).
      Some patients did not complain of any urinary frequency or stress incontinence
      following hysterectomy, but this figure did not differ significantly (p > 0.05).
      Maximal urethral closure pressure and maximal cystometric capacity demonstrated
      significant increases for both groups following surgery. CONCLUSIONS: The results
      indicated that total hysterectomy, either laparoscopic or total abdominal
      hysterectomy, did not significantly increase the subjective and objective
      incidence of vesicourethral dysfunction. On the contrary, some patients
      experience a substantial improvement of pre-existing urinary frequency or stress
      incontinence, partly as a result of an increase in the maximal urethral closure
      pressure and total bladder capacity following hysterectomy.

PMID- 12230060
TI  - A survey of entry techniques and complications of members of the Australian
      Gynaecological Endoscopy Society.
AB  - OBJECTIVE: To identify various aspects of laparoscopic entry technique and
      visceral injury experienced by members of the Australian Gynaecological Endoscopy
      Society (AGES). DESIGN: A retrospective mailed survey. SAMPLE: All members of the
      Australian Gynaecological Endoscopy Society (AGES). MAIN OUTCOME MEASURES:
      Numbers of bowel and major retroperitoneal vascular injuries experienced, entry
      techniques utilised, alternative entry sites. RESULTS: Of the respondents, 73%
      use a Veress needle entry. In subjects with an increased risk of peri-umbilical
      adhesions 83% of respondents use an alternate site of entry, 66% of which use
      Palmer's point. Sixty-four per cent of respondents had experienced one or more
      bowel injuries, 21% had experienced major retroperitoneal vascular injury, 33% of
      respondents had no plan in place for the management of vascular injury and 51% of
      respondents would alter their clinical practice if accepted entry technique
      guidelines were available. CONCLUSIONS: The majority of respondents use the
      Veress needle method of entry, have had at least one entry-related bowel injury
      and use Palmer's point as an alternative entry site in high-risk subjects. The
      majority of subjects would alter their clincal practice if accepted entry
      technique guidelines were available.

PMID- 12230061
TI  - A prospective randomised double-blind placebo controlled trial to assess whether
      gas drains reduce shoulder pain following gynaecological laparoscopy.
AB  - OBJECTIVE: To assess the effects on patient discomfort of an intraabdominal
      passive gas drain left for four hours postoperatively following gynaecologic
      laparoscopic surgery. DESIGN: A prospective randomised double-blinded placebo
      controlled trial. SETTING: University tertiary hospital and private hospital.
      POPULATION OR SAMPLE: Eighty women having a laparoscopic gynaecological procedure
      for benign disease. METHODS: A drain was placed via the umbilical port at the
      conclusion of the surgical procedure and was removed four hours postoperatively.
      The researcher, assessor and patient were all blinded as to the patency or
      occlusion of the drain. Patients were asked to complete questionnaires at regular
      intervals up to five days postoperatively. MAIN OUTCOME MEASURES: Visual analogue
      scale (VAS) to assess overall pain, shoulder and chest pain, abdominal pain,
      bloating and energy prior to surgery and at intervals up to five days
      postoperatively. RESULTS AND CONCLUSIONS: No complications were attributed to the
      presence and withdrawal of the drain tube. Shoulder pain following operative or
      diagnostic laparoscopy was significantly reduced for 12, 24, 48 and 72 hours by
      the presence of a patent passive gas drain for the first four hours
      postoperatively. The drains were easy to use and had no associated morbidity We
      recommend that in the absence of the need for an active drain, all patients
      undergoing laparoscopy should have a gas drain inserted for a period of four
      hours after the completion of the procedure.

PMID- 12230062
TI  - An Australasian survey of the management of hydrosalpinges in women due to
      undergo in vitro fertilisation.
AB  - OBJECTIVE: To ascertain current practice of surgical interventions for women with
      hydrosalpinges prior to in vitro fertilisation and to compare this with a
      subsequent systematic review of the literature. DESIGN: Survey. SETTING:
      Specialists in Australasian IVF clinics. METHODS: Questionnaire sent to all
      specialists in Australasian IVF clinics via the clinical directors of these
      units. RESULTS: There were 79 respondents from 33 fertility clinics. Although
      only 66% expressed a belief that there was convincing evidence of an improvement
      in pregnancy outcomes from surgical treatment for hydrosalpinges prior to in
      vitro fertilisation, 94% currently offer surgical treatment for hydrosalpinges
      prior to in vitro fertilisation, 32% always and 62% only in selected cases. Of
      the 74 respondents offering surgery, all but three expressed a preference for the
      laparoscopic approach. Of those offering surgery, 89% performed unilateral or
      bilateral salpingectomy depending whether unilateral or bilateral hydrosalpinges
      were present, 5% routine bilateral salpingectomy 14% proximal tubal occlusion
      with clips, 24% salpingostomy, 7% ultrasound-guided needle aspiration of
      hydrosalpinges at the time of egg collection. CONCLUSIONS: The diverse practice
      among Australasian fertility specialists reflects the apparent conflict in the
      literature prior to this survey. A Cochrane Review has now demonstrated the
      efficacy of laparoscopic salpingectomy in improving the odds of live birth for
      women with hydrosalpinges due to undergo in vitro fertilisation. It will be
      interesting to review whether this leads to greater uniformity of practice in the
      coming years.

PMID- 12230063
TI  - Laparoscopic diagnosis of endometriosis.
AB  - OBJECTIVE: To consider and explain the possibility of difficulties in diagnosis
      of endometriosis at previous laparoscopy DESIGN: Retrospective patient record
      review. SETTING: The Endometriosis Care Centre of Australia and the private
      practices of authors. SAMPLE: Two hundred and fifteen patients with clinical
      evidence of endometriosis examined laparoscopically between March 1999 and May
      2001. MAIN OUTCOME MEASURES: Confirmation of endometriosis by histological
      biopsy. RESULTS: Endometriosis was confirmed in 168 of the 215 women. Of these
      women 38 had a previous negative laparoscopy within 12 months of the current
      laparoscopy. CONCLUSIONS: It is possible that in some of the patients, who
      previously had a negative laparoscopy, endometriosis was not recognised. Possible
      reasons for difficulty in diagnosis have been identified and techniques to
      improve diagnosis suggested. This retrospective study was performed to consider
      and explain the possibility of difficulties in diagnosis of endometriosis at
      previous laparoscopy.

PMID- 12230064
TI  - Total laparoscopic hysterectomy: a new option for removal of the large myomatous
      uterus.
AB  - This is the first report of a series of women who underwent total laparoscopic
      hysterectomy (TLH) to remove a large myomatous uterus weighing more than 390 g.
      The case history notes of 21 women undergoing TLH in both the private and public
      sectors of Flinders Endogynaecology were studied. The mean uterine weight was
      534.7 g (390-1,022 g). The mean operating time was 155.0 +/- 56.1 minutes and
      mean blood loss was 297.6 mL (50-1,000 mL). The mean hospital stay was 3.2 +/-
      1.0 days. The two complications were a post-operative deep venous thrombosis
      (DVT) and an estimated blood loss of 1000 mL in separate cases. Total
      laparoscopic hysterectomy is a low morbidity procedure offering a new option for
      the removal of the large myomatous uterus and avoidance of abdominal hysterectomy

PMID- 12230065
TI  - IVF and tubal pathology--not all bad news.
AB  - OBJECTIVES: In light of evidence that hydrosalpinges compromise the chance of
      success of in vitro fertilisation (IVF), the aim of this study was to analyse the
      results of IVF treatment at our clinic in relation to the cause for infertility
      and to make inferences concerning the impact of mild tubal disease on IVF
      outcome. DESIGN: Retrospective observational study. SETTING Tertiary fertility
      clinic in New Zealand. POPULATION: Nine hundred and six consecutive cycles among
      639 couples receiving IVF treatment in the six-year period 1995-2000 inclusive.
      METHODS: Data extraction from the clinic database. RESULTS: The clinical
      pregnancy rate of 17.5% per ovarian stimulation cycle and 23.9% per embryo
      transfer for the cycles of couples with tubal disease as the only cause for
      infertility was not significantly different from the clinical pregnancy rate of
      15.4% per ovarian stimulation cycle and 24.1% per embryo transfer for all other
      couples undergoing IVF. In the cycles of women with tubal disease, the clinical
      pregnancy rate of 6.6% per ovarian stimulation cycle where other causes for
      infertility were also present, was significantly lower than the clinical
      pregnancy rate of 17.5% where tubal factor alone was present. In the cycles of
      couples with multiple causes for infertility, where the overall pregnancy rate
      was 10.9% per ovarian stimulation cycle, there was no significant difference in
      pregnancy rate between those whose multiple causes included tubal disease (6.6%
      per ovarian stimulation cycle) and those whose multiple causes did not include
      tubal disease (17.5% per ovarian stimulation cycle). CONCLUSION: The overall
      population of women with tubal disease as the sole cause for infertility
      (including women with hydrosalpinges and those with non-hydrosalpinx tubal
      disease) does not have an overall reduced likelihood of success at IVF. This
      suggests that non-hydrosalpinx tubal disease does not compromise the chance of
      success from IVF. Surgical treatment prior to IVF for the milder forms of tubal
      disease is not warranted.

PMID- 12230066
TI  - A simple trainer for the loop electrosurgical excision procedure.
AB  - This article describes the construction and use of a simple trainer for the loop
      electrosurgical excision procedure (LEEP), also known as large loop excision of
      the cervical transformation zone (LLETZ).

PMID- 12230067
TI  - Immediate and associated complications of hysterectomy for benign disease.
AB  - Abdominal and vaginal hysterectomy are common operations for benign
      gynaecological conditions. Though safe operations, they are not without
      complications. Good medical practice requires that patients be fully counselled
      regarding risks involved in undergoing medical interventions. This can only be
      done by regular review of local practice and comparison with national and
      international standards. We have reviewed 502 case notes of patients who have
      undergone a hysterectomy for benign conditions over an 18-month period.

PMID- 12230068
TI  - Complications of laparoscopic hysterectomy: the Monash experience.
AB  - A retrospective review of medical records was performed to assess the incidence
      and type of significant complications encountered during laparoscopic
      hysterectomy Two hundred and sixty-five consecutive patients were reviewed
      between the years 1994 and August 2001. Two hundred and thirty-two laparoscopic
      vaginal hysterectomies and 33 total laparoscopic hysterectomies were performed.
      The operations were performed at Monash Medical Centre, a Melbourne tertiary
      public hospital, and two Melbourne private hospitals, by three surgeons. Ten
      significant complications occurred. There were two cases of ureteric fistula, two
      bladder injuries, two bowel obstructions, two postoperative haematomas, one case
      of a bladder fistula and one superficial epigastric artery injury. In-patient
      stay ranged from two to six days. Our complication and in-patient stay rates are
      consistent with previously reported rates.

PMID- 12230069
TI  - Laparoscopic management of a case of abdominal ectopic pregnancy.

PMID- 12230070
TI  - Advancing surgical techniques during abdominal sacrocolpopexy: the case for
      interdisciplinary discussions over coffee sacrocolpopexy:.

PMID- 12230071
TI  - Diagnosis and management of giant para-ovarian cysts by combined endovaginal
      ultrasound imaging and minimal access surgery.

PMID- 12230072
TI  - Bladder stone following Stamey's colposuspension.

PMID- 12230073
TI  - Suture perforation of the bladder in Burch colposuspension.

PMID- 12230074
TI  - Laparoscopic-assisted Vecchietti procedure for creation of a neovagina: an
      analysis of five cases.
AB  - The aim of this study was to review the functional and psychological outcomes of
      subjects with vaginal aplasia undergoing a laparoscopic creation of a neovagina
      (Vecchietti procedure). A semi-structured telephone interview was undertaken of
      five consecutive subjects who underwent the procedure in the preceding three
      years. Information was obtained with regard to the operation, immediate post
      operative period, complications experienced, sexual function and improvements in
      general and psychological well-being. A functioning neovagina was formed in all
      subjects. All sexually active women noted satisfactory intercourse with
      significant improvements in self-confidence, self-esteem and general well-being
      up to three years post-operatively.

PMID- 12230075
TI  - Small bowel obstruction during pregnancy: a case report.

PMID- 12230076
TI  - Abdomino-pelvic mass and positive pregnancy test in an XY female.

PMID- 12230077
TI  - Re: New Zealand evidence-based guidelines for management of uterine fibroids.

PMID- 12230078
TI  - A reassessment of options for the management of placenta praevia percreta.

PMID- 12230079
TI  - The management of chronic vulval discomfort in Australia.

PMID- 12230080
TI  - The serious clinical problem of chronic vulvar disease.

PMID- 12230081
TI  - Aging and schizophrenia: current health services research and recommendations.
AB  - Little is known about the functioning and health care use of older patients with
      schizophrenia. Understanding the use patterns of older patients with
      schizophrenia, a rapidly growing population, will inform health care planners and
      policy makers who make decisions about resource allocation and program
      development. The results are presented from a large-scale study to examine the
      relationship between age and the use of health services and level of functioning
      in patients with schizophrenia. Older adults with schizophrenia experienced fewer
      psychiatric hospitalizations but, once hospitalized, had longer inpatient stays.
      In contrast, older patients had fewer outpatient psychiatric visits and more
      medical outpatient visits and medical hospitalizations than younger individuals.
      The relatively lower use of outpatient psychiatric care by older patients with
      schizophrenia suggests that there may be barriers to accessing these services.
      When older patients are hospitalized for psychiatric reasons, their stays are
      longer. The implications of these findings are discussed.

PMID- 12230082
TI  - Aging-related issues in bipolar disorder: a health services perspective.
AB  - Among the elderly, bipolar disorder is a significant public health problem, often
      leading to functional impairment and substantial use of health care resources.
      There has been a growing awareness regarding the manifestations of bipolar
      disorder among older adults owing to both changes in national demographics and
      developing sophistication in the treatment of bipolar illness. Bipolar disorder
      accounts for 5% to 19% of mood disorder presentations in the elderly, although a
      clear picture of the exact prevalence of bipolar disorder among older adults in
      the community is still lacking. Data from treatment centers give a somewhat
      unreliable picture of the true prevalence and manifestations of bipolar disorder
      in the general population as elderly patients tend to underuse mental health
      systems, under-report psychiatric symptoms, and are often treated in
      nonhospital/clinic settings, such as nursing homes. Factors of particular
      relevance in late-life bipolar disorder include age of onset, symptom
      presentation/recognition, secondary mania, psychiatric and medical comorbidity,
      and response to treatment. Future mental health services research must further
      explore these issues to optimize care for older adults with bipolar disorder.

PMID- 12230083
TI  - Late-life depression and mental health services in primary care.
AB  - Mental health services in the treatment of late-life depression are critical in
      the primary care arena. A significant proportion of elderly patients experience
      depression, a problem causing a far-reaching impact on morbidity, mortality, and
      quality of life. A number of barriers may prevent effective depression treatment
      including negative physician and patient attitudes toward the stigma of
      depression, somatically focused clinical presentations, health care plan
      constraints, and competing medical demands, as well as gender and geographic
      isolation. Screening for depression in primary care settings is not always
      standard fare as physicians may feel confident in their diagnostic abilities.
      Research addressing effective depression treatment in the primary care setting
      has been limited to few clinical trials and physician-focused academic detailing.
      Future research should address real-world scenarios encountered by the primary
      care physician in their treatment of the "old-old" patient with complex medical
      comorbidities and functional decline.

PMID- 12230085
TI  - Complexity in late-life depression: impact of confounding factors on diagnosis,
      treatment, and outcomes.
AB  - Late-life depression is a heterogeneous syndrome. Although depression in elderly
      patients is highly treatable, a number of factors or confounds create complexity
      in its overall management. Patient factors, such as medical illness,
      neuropsychiatric comorbidity, and race, may interact with provider factors to
      make management more complex. Outcomes and services research indicate that these
      factors, particularly medical illness, affect whether late-life depression is
      appropriately detected, diagnosed, and treated. Attention to such factors must be
      included in an agenda for mental health services research, with emphasis on the
      delivery of effective treatment to elderly patients with depression and improved
      outcomes in clinical settings.

PMID- 12230084
TI  - Pharmacologic treatment of depression in nursing home residents: a mental health
      services perspective.
AB  - Over the past 10 to 15 years, there has been marked progress in clinical research
      on depression in nursing home residents. There have also been significant changes
      in federal regulations designed to improve the quality of care. In 1987, only 10%
      of nursing home residents diagnosed with depression were receiving treatment, but
      by 1999,25% of all residents were receiving antidepressants. We report on two
      studies: one demonstrating that treatment for depression has a substantial,
      ecologically relevant impact in the nursing home and another demonstrating that
      profound changes have occurred in the clinical epidemiology of depression and its
      treatment in the nursing home. Although the numbers of nursing home residents
      receiving antidepressants have increased dramatically, there are now second
      generation problems that must be addressed to ensure the delivery of effective
      treatment. Developing models to ensure quality of care will require focused
      mental health services research.

PMID- 12230086
TI  - Atypical antipsychotics in Parkinson-sensitive populations.
AB  - Drug-induced iatrogenic hallucinations and psychosis occur in about 30% of
      Parkinson's disease (PD) patients and are the single most important precipitant
      for nursing home placement, which carries a grave prognosis. In addition,
      parkinsonism is a frequent accompaniment to the more common dementing syndromes,
      Alzheimer's disease (AD), vascular dementia, and dementia with Lewy bodies (DLB).
      The five most recent antipsychotic drugs approved by the Food and Drug
      Administration in the United States have been marketed as "atypical"
      antipsychotics (AA) due to their relative freedom from extrapyramidal symptoms
      when used in schizophrenia patients. The use of these newer antipsychotic drugs
      in PD and other parkinson-sensitive populations represents the most stringent
      test to their freedom from motor side effects. To date, clozapine, risperidone,
      olanzapine, and quetiapine have been studied in parkinson-vulnerable populations.
      This article reviews the data and highlights the differences that these four
      drugs have on motor function. It also emphasizes the challenges in evaluating the
      available data on the motor effects of AA, especially on the non-PD elderly and
      cognitively impaired population. Suggestions are made for future research to
      improve the interpretability of these studies.

PMID- 12230087
TI  - A transcultural study of agitation in dementia.
AB  - Agitation is one of the most troublesome behaviors in demented patients. It is
      etiologically heterogeneous and has varied associated behaviors. To explore the
      transcultural differences in the manifestation of agitation, we evaluated 50
      consecutive Alzheimer's disease (AD) patients in three countries (Taiwan, Italy,
      and the United States) using the Neuropsychiatric Inventory (NPI) and the Mini
      Mental State Examination (MMSE). In a focused analysis, only patients with
      composite NPI scores > 2 for agitation were selected, with similar levels of
      disease severity as measured by the MMSE, from the three groups (n = 15 per
      group) to evaluate culturally specific correlates of agitation. Agitated
      Taiwanese had significantly more hallucinations than either Italian or American
      patients. Agitated Italian patients had significantly more apathy than both
      Taiwanese and American patients. Cultural factors may influence the manifestation
      of agitation more than a common underlying neuropathology. Management strategies
      targeting unique behavioral instigators of agitation may be specific for
      different ethnic groups.

PMID- 12230088
TI  - Hashimoto's encephalopathy in the elderly: relationship to cognitive impairment.
AB  - Hashimoto's encephalopathy (HE) is a steroid-responsive encephalopathy associated
      with high titers of antithyroid antibodies. To date, 57 pediatric-, adult-, and
      elderly-onset cases have been described in the literature. The clinical picture
      is pleomorphic, and cognitive impairment is a frequently reported symptom. We
      report the case of a patient with slowly progressive cognitive impairment
      possibly caused by HE. The issue of the differential diagnosis with primary
      dementia is discussed. A review of cases of HE showing cognitive deterioration is
      also presented, and factors possibly related to characteristics of cognitive
      impairment and outcome after therapy are considered.

PMID- 12230089
TI  - Technical and analytical advances in pulmonary ventilation SPECT with xenon-133
      gas and Tc-99m-Technegas.
AB  - This paper describes the recent advances in technical and analytical methods in
      pulmonary ventilation SPECT studies, including a respiratory-gated image
      acquisition of Technetium-99m (99mTc)-labeled Technegas SPECT, a fusion image
      between Technegas SPECT and chest CT images created by a fully automatic image
      registration algorithm, and a three-dimensional (3D). display of xenon-133
      (133Xe) gas SPECT data, and new analytical approaches by means of fractal
      analysis or the coefficient of variations of the pixel counts for Technegas SPECT
      data. The respiratory-gated image acquisition can partly eliminate problematic
      effects of the SPECT images obtained during non-breath-hold. The fusion image is
      available for routine clinical use, and provides complementary information on
      function and anatomy. The 3D displays of dynamic 133Xe SPECT data are helpful for
      accurate perception of the anatomic extent and locations of impaired ventilation,
      and the assessment of the severity of ventilation abnormalities. The new
      analytical approaches facilitate the objective assessment of the degrees of
      ventilation abnormalities.

PMID- 12230090
TI  - Regional differences in distribution volume of I-123 IMP in the human brain:
      effect on CBF calculated by ARG method.
AB  - OBJECTIVE: Two methods of quantitating cerebral blood flow (CBF) with iodine-123
      labeled N-isopropyl-p-iodoamphetamine (I-123 IMP) and a two-compartment model had
      been proposed; one is the table look-up (TLU) method and the other is the
      autoradiographic (ARG) method. The TLU method provides values of the cerebral
      blood flow (CBF) values and distribution volume of I-123 IMP (Vd) independently.
      In the ARG method, a fixed Vd is applied for the entire brain to calculate CBF.
      Our purpose was to evaluate regional differences in Vd in the human brain, or
      possible effects of regional differences in Vd on CBF calculated by the ARG
      method. METHODS: In the present study, two SPECT scans were acquired from each of
      eight normal subjects (aged 44.0 +/- 16.7) at 40 min and 180 min of mid-scan-time
      after intravenous 1 min infusion of 111 MBq IMP. A single arterial blood sampling
      was performed 10 min after the IMP infusion. All images were anatomically
      normalized and analyzed with SPM99 and Matlab. We generated CBF and Vd images for
      each subject by the TLU method and evaluated differences in Vd among brain
      structures. We subsequently generated another set of CBF images by the ARG method
      and examined differences between CBF calculated by the TLU method and that by the
      ARG method. RESULTS: Significant main effects of subject and brain structure in
      Vd were observed (two-way ANOVA). Vd values were higher in the deep gray matter
      than in the cerebral cortical regions. Among the cerebral cortical regions, no
      significant difference in Vd was observed. In spite of the significant
      differences in Vd among the brain structures, the voxel-by-voxel analyses as well
      as the ROI analyses revealed no statistically significant difference between CBF
      calculated by the TLU method and that by the ARG method. CONCLUSIONS: Although
      regional differences in Vd were observed, the present results support the
      assumption that a fixed Vd does not cause significant error in the calculation of
      CBF by the ARG method.

PMID- 12230091
TI  - Evaluation of a commercial PET tomograph-based system for the quantitative
      assessment of rCBF, rOEF and rCMRO2 by using sequential administration of 15O
      labeled compounds.
AB  - The purpose of this study was to develop a reliable and practical strategy that
      generates quantitative CBF and OEF maps accurately from PET data sets obtained
      with 15O-tracers. Sequential sinogram data sets were acquired after the
      administration of 15O-tracers, and combined single-frame images were obtained.
      The delay time between sampled input function and the brain was estimated from
      the H2(15)O study with the whole brain and the arterial time-activity curves
      (TACs). The whole-brain TACs were obtained from the reconstructed images (image
      base method) and the sinogram data (sinogram-base method). Six methods were also
      evaluated for the dead-time and decay correction procedures in the process of
      generating a single-frame image from the dynamic sinogram. The estimated delay
      values were similar with both the sinogram-based and image-based methods. A
      lumped correction factor to a previously added single-frame sinogram caused an
      underestimation of CBF, OEF and CMRO2 by 16% at maximum, as compared with the
      correction procedure for a short sinogram. This suggested the need for a dynamic
      acquisition of a sinogram with a short interval. The proposed strategy provided
      an accurate quantification of CBF and OEF by PET with 15O-tracers.

PMID- 12230092
TI  - Serial assessment of left ventricular performance at rest and during bicycle
      exercise by ECG-gated myocardial perfusion SPECT.
AB  - The present study evaluates left ventricular performance during exercise by ECG
      gated myocardial perfusion SPECT with short-time data collection. METHODS: The
      study population consisted of 10 healthy volunteers (Group N) and 9 patients with
      ischemic heart disease (Group I). Seven patients in Group I had a history of
      prior myocardial infarction. Rest ECG-gated SPECT was performed 40 min after an
      injection of Tc-99m-tetrofosmin (555-740 MBq). After resting data acquisition,
      Group N underwent up to two 5-min stages of exercise (75 and 125 watts) on a
      detachable bicycle ergometer. The Group I patients all underwent symptom-limited,
      maximal testing on the ergometer. ECG-gated SPECT data were acquired from both
      groups for 3 min at rest and during the last 3 min of each exercise stage.
      RESULTS: Significant increases occurred in LVEF from rest to peak stress in both
      groups (from 55.4 +/- 5.8 to 66.6 +/- 4.1% in group N, p < 0.0001; from 49.0 +/-
      12.8 to 56.7 +/- 13.8% in Group I, p < 0.001). The LVESV values significantly
      decreased to peak stress in Group N (from 49.9 +/- 13.1 to 37.8 +/- 10.0 ml, p <
      0.0001), whereas LVEDV did not change (from 110.6 +/- 18.9 to 112.0 +/- 19.0 ml).
      In contrast, the LVESV values at rest and under peak stress were similar in Group
      I (from 52.6 +/- 23.9 to 51.7 +/- 31.4 ml) and LVEDV in Group I at peak exercise
      tended to increase (from 102.8 +/- 36.7 to 111.3 +/- 39.0 ml). The changes in
      LVESV from rest to peak stress were significantly different between Groups N and
      I (-12.1 +/- 6.3 vs. -0.9 +/- 11.6 ml, p < 0.02). CONCLUSION: ECG-gated SPECT
      with short-time data collection can assess left ventricular function during
      exercise and may offer useful information for evaluating patients with ischemic
      heart disease.

PMID- 12230093
TI  - Clinical impact of whole body FDG-PET on the staging and therapeutic decision
      making for malignant lymphoma.
AB  - OBJECTIVES: The aim of this study is to evaluate the clinical impact of whole
      body FDG-PET for the pre-therapeutic evaluation of malignant lymphoma and
      compared to that of 67Ga-scintigraphy when added to non-RI examinations. METHODS:
      We examined 46 patients with malignant lymphoma including 42 newly diagnosed
      cases and 4 relapsed cases. Whole-body FDG-PET was started 63 minutes after the
      administration of FDG with ECAT EXACT HR+. The clinical stage of each patient was
      determined based on the results of a non-RI examination (consisting of physical
      examination, CT, gastrointestinal studies and bone marrow aspiration), 67Ga
      planar images and FDG-PET. Discrepant findings were verified based on the
      response to treatment and the findings of a follow-up examination more than 6
      months after treatment. Finally, 152 nodal regions and 19 extranodal tissues were
      found to be involved by disease. RESULTS: In the 152 nodal lesions, FDG-PET
      detected 54 nodal lesions in addition to 98 lesions detected by non-RI
      examinations, whereas 67Ga-scintigraphy detected 14 additional lesions. The
      sensitivity of non-RI, non-RI + 67Ga and non-RI + FDG was 64.5%, 73.7% and
      100.0%, respectively. In 19 extranodal lesions, FDG-PET detected 5 extranodal
      lesions in addition to 13 lesions detected by non-RI examinations, whereas 67Ga
      scintigraphy detected 1 additional lesion. The sensitivity of non-RI, non-RI +
      67Ga and non-RI + FDG was 68.4%, 73.7% and 94.7%, respectively. When combining
      the FDG-PET findings with the non-RI findings, the improvement of the
      detectability was much higher than that when 67Ga findings were combined to the
      non-RI findings. For the staging of lymphoma, the non-RI and non-RI + 67Ga
      findings accurately diagnosed 76.1% and 80.4%, respectively, whereas the non-RI +
      FDG findings accurately diagnosed 82.6%. Finally, FDG-PET resulted in changes in
      the clinical management of 8 patients (17.4%). CONCLUSIONS: FDG-PET offers more
      information in addition to the findings of conventional diagnostic methods than
      67Ga-scintigraphy in order to accurately detect malignant lymphoma. FDG-PET can
      therefore play an important role in therapeutic decision making on lymphoma.

PMID- 12230094
TI  - Atypical finding of brain Tc-99m-ECD SPECT imaging in herpes simplex
      encephalitis.
AB  - Lesions in acute herpes simplex encephalitis (HSE) have been reported to show
      decreased uptake of Tc-99m ethyl cysteinate dimer (ECD). A patient with acute HSE
      displaying a lesion in the left temporal lobe was evaluated by means of Tc-99m
      ECD single-photon emission computed tomography (SPECT). Dynamic SPECT images
      indicated regionally increased uptake of tracer in the ipsilateral temporal lobe
      in early phases, followed by slight washout of Tc-99m ECD from the lesion. Static
      SPECT images revealed increased tracer uptake in the same region. MRI later
      demonstrated that the HSE lesion involved the whole cortex of the temporal lobe
      on the affected side. These findings suggest that acute HSE lesions do not always
      exhibit hypoactivity on static Tc-99m ECD SPECT, and that dynamic Tc-99m ECD
      SPECT may help physicians diagnose acute HSE.

PMID- 12230095
TI  - Thallium-201 accumulation in a patient with brain abscess.
AB  - A 57-year-old man was admitted to our hospital because of high fever and
      generalized tonic seizure. Brain magnetic resonance imaging (MRI) delineated
      multiple abnormal intensity areas. Thallium-201 (201Tl) scintigraphy revealed
      abnormal uptake in the brain. The imaging findings did not allow definitive
      exclusion of brain tumor, even though brain abscess was the more strongly
      suspected diagnosis. As the patient improved, the multiple abnormal intensity
      areas in the brain on MRI and the abnormal areas of accumulation on 201Tl
      scintigraphy were reduced, and eventually completely disappeared. A final
      diagnosis of brain abscess was therefore made. Since relatively few studies have
      reported 201Tl accumulation in cases of brain abscess, we report here our patient
      in whom the changes in the accumulation of 201Tl in a brain abscess were observed
      over time.

PMID- 12230096
TI  - A patient with two thyroid papillary carcinomas demonstrating hot and cold
      lesions on 113I thyroid scintigraphy.
AB  - A 44-year-old euthyroid woman had two palpable nodules in the thyroid gland. 123I
      thyroid scintigraphy showed a hot nodule in the right lobe and a cold one in the
      left lobe. Total thyroidectomy was performed, and histopathologic examination
      revealed that both tumors contained papillary carcinoma. Thus, hot nodules on a
      thyroid scintigram with 123I do not necessarily preclude malignancy.

PMID- 12230098
TI  - SPECT imaging with off-set detector system: comparison of sampling angles 2, 4
      and 6 degrees.
AB  - PURPOSE: We evaluated an off set reconstruction method for single photon emission
      computed tomography (SPECT), and compared it with the conventional on set
      reconstruction method, using sampling angles of 2, 4, and 6 degrees. METHOD: A
      triple-detector system was used. In the off-set acquisition, sampling angles of
      the opposite detector were shifted 1/2 of the sampling angles of 2, 4, and 6
      degrees. For example, when projection data were acquired every 6-degrees
      (sampling angle = 6 degrees), the projection angles were at 0 degrees, 6 degrees,
      12 degrees, and 174 degrees with one detector, and 177 degrees, 183 degrees, 189
      degrees, and 357 degrees with the other, opposite, detector. The conventional on
      set reconstruction images were compared with an off set reconstruction for a pool
      phantom of uniform concentration, a hot rods phantom, a myocardial phantom, and a
      human study. RESULTS: The off set reconstruction method was better at all three
      sampling angles. FWHM (mm) were 11.02 at off-set versus 11.17 at on-set (sampling
      angle 2 degrees), 11.13 at off-set versus 11.48 at on-set (sampling angle 4
      degrees), and 11.24 at off-set versus 11.64 at on-set (sampling angle 6 degrees),
      respectively. In human myocardium SPECT, visualization of the interventricular
      septum and cardiac cavity was improved. CONCLUSION: Off set reconstruction by
      means of filtered back projection will be an efficient sampling mode, having a
      larger number of effective projection angles.

PMID- 12230097
TI  - Radioguided surgery in primary hyperparathyroidism.
AB  - Surgical neck exploration is usually made in primary hyperparathyroidism (PHPT).
      Localization of the adenoma or detection of hyperplasia may reduce the operation
      period and limit the extent of the surgery. In this study the effficacy of
      preoperative Tc-99m MIBI scintigraphy and intraoperative gamma probe was
      evaluated. MATERIALS AND METHODS: Six patients with PHPT had preoperative Tc-99m
      MIBI parathyroid scintigraphy and intraoperative gamma probe (IGP) was used in
      surgical neck exploration. RESULTS: Parathyroid adenoma was observed in 2/6
      patients on scintigraphy in the right retroclavicular region and the left lobe of
      the thyroid. Both of them were clearly detected by IGP during the surgery and
      easily removed by the surgeon in a short time (35 min) with a small incision.
      Pathologic examination confirmed the parathyroid adenoma. No abnormal MIBI uptake
      was not observed in scintigraphy in 4/6 patients. Subtotal parathyroidectomy was
      performed in these patients. CONCLUSION: Preoperative Tc-99m MIBI scintigraphy
      and the use of IGP may limit the exploration and also the operation time and
      reduce surgical complications.

PMID- 12230099
TI  - What is the diagnosis? Lemierre's syndrome.

PMID- 12230100
TI  - Fructosamine assay using albumin extracted from serum.
AB  - Albumin extracted from serum by a simple technique using trichloroacetic acid and
      ethanol has been applied to a fructosamine assay using nitroblue tetrazolium. A
      fructosamine assay using extracted albumin sample was carried out without
      interference from low molecular weight substances with reducing activities and
      other proteins with varying concentrations, half-lives and reducing activities. 1
      Deoxy-1-p-toluidino-D-fructose (DTF) was selected as a calibrator for the assay
      because it is a stable Amadori reaction product with a constant glycation rate.
      Albumin fructosamine value was calculated using the calibration curve of DTF. The
      corrected albumin fructosamine value was expressed as the amount of albumin
      fructosamine per gram of extracted albumin taking into consideration the
      variation in albumin concentrations in sera from patients. The corrected albumin
      fructosamine values correlated more closely with the fasting blood glucose levels
      (r=0.735) than the serum fructosamine values corrected for albumin concentrations
      (r=0.514) (p<0.05).

PMID- 12230101
TI  - GTP gamma S-stimulated lysosomal lysis dependent on the assembly of adaptor
      protein on lysosome.
AB  - Cytosol treated with guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) destroys the
      dextran-loaded lysosomes (J. Biochem., 123, 637 (1998)). The transfer of the ADP
      ribosylation factor (ARF) from the cytosol to the lysosomal membrane is necessary
      for this lysis to occur. The role of ARF in the biogenesis of the Golgi complex
      is to generate high-affinity membrane-binding sites for the heterotetrameric
      adaptor protein complex in Golgi membranes. We have found that ARF also recruits
      the adaptor protein to lysosomes. The recruitment of protein coats for vesicles
      is necessary for the GTPgammaS-stimulated lysis of lysosomes. The GTPgammaS
      induced lysis proceeded via a process similar to that for the assembly of coated
      proteins to coated vesicles, which serve to transport proteins between
      intracellular organelles.

PMID- 12230102
TI  - Frequency and genetic characterization of multidrug-resistant mutants of
      Staphylococcus aureus after selection with individual antiseptics and
      fluoroquinolones.
AB  - The frequency of generation of multidrug-resistant mutants of Staphylococcus
      aureus was examined by selection with various antiseptics and fluoroquinolones
      and the mutated genes were characterized. Multidrug-resistant mutants with
      mutation of the region between the promoter and structural regions of the norA
      gene were generated more frequently during selective pressure with antiseptics
      than during selective pressure with FQs. We also obtained evidence for the
      existence of at least one other gene related to resistance to antiseptics and
      fluoroquinolones on the chromosome of S. aureus in addition to norA gene.

PMID- 12230103
TI  - Beneficial effects of Hippophae rhamnoides L. on nicotine induced oxidative
      stress in rat blood compared with vitamin E.
AB  - The aim of this study was to determine the effects of Hippophae rhamnoides L.
      extract (HRe-1) and also vitamin E as a positive control on nicotine-induced
      oxidative stress in rat blood, specifically alterations in erythrocyte
      malondialdehyde (MDA) level, activities of some erythrocyte antioxidant enzymes,
      and plasma vitamin E and A levels. The groups were: nicotine (0.5 mg/kg/d,
      intraperitoneal, i.p.); nicotine+vitamin E (75 mg/kg/d, intragastric, i.g.);
      nicotine+HRe-1 (1 ml/kg/d, i.g.); and control group (receiving only vehicles).
      There were 8 rats per group and the supplementation period was 3 weeks. Nicotine
      induced increase in erythrocyte MDA level was prevented by both HRe-1 and vitamin
      E. Nicotine-induced decrease in erythrocyte superoxide dismutase (SOD) activity
      was prevented by HRe-1, but not vitamin E. HRe-1 increased the erythrocyte
      glutathione peroxidase (GSH-Px) activity compared with nicotine and the vitamin E
      groups. Catalase activity was not affected. Vitamin E supplementation increased
      plasma vitamin E level. Plasma vitamin A level was higher in both vitamin E and
      HRe-1 supplemented groups compared with nicotine and control groups. The results
      suggest that HRe-1 extract can be used as a dietary supplement, especially by
      people who smoke, in order to prevent nicotine-induced oxidative stress.

PMID- 12230104
TI  - Inhibitions of histamine release and prostaglandin E2 synthesis by mangosteen, a
      Thai medicinal plant.
AB  - The fruit hull of mangosteen, Garcinia mangostana L. has been used as a Thai
      indigenous medicine for many years. However, its mechanism of action as a
      medicine has not been elucidated. The present study was undertaken to examine the
      effects of mangosteen extracts (100% ethanol, 70% ethanol, 40% ethanol and water)
      on histamine release and prostaglandin E2 synthesis. We found that the 40%
      ethanol extract of mangosteen inhibited IgE-mediated histamine release from RBL
      2H3 cells with greater potency than the water extract of Rubus suavissimus that
      has been used as an anti-allergy crude drug in Japan. All extracts of mangosteen
      potently inhibited A23187-induced prostaglandin E2 synthesis in C6 rat glioma
      cells, while the water extract of Rubus suavissimus had no effect. The 40%
      ethanol extract of mangosteen inhibited the prostaglandin E2 synthesis in a
      concentration-dependent manner with relatively lower concentrations than the
      histamine release. In addition, passive cutaneous anaphylaxis (PCA) reactions in
      rats were significantly inhibited by this ethanol extract as well as by the water
      extract of Rubus suavissimus. These results suggest that the 40% ethanol extract
      of mangosteen has potent inhibitory activities of both histamine release and
      prostaglandin E2 synthesis.

PMID- 12230105
TI  - Induction of nitric oxide synthase by Oldenlandia diffusa in mouse peritoneal
      macrophages.
AB  - Oldenlandia diffusa (OD) has been used to treat malignant tumors. In this study
      using mouse peritoneal macrophages, we have examined the mechanism by which OD
      regulates nitric oxide (NO) production. When OD (1 mg/ml) was used in combination
      with 10 U/ml of recombinant interferon-gamma (rIFN-gamma), there was a marked
      cooperative induction of NO production (36.13+/-7.12 microM) by the Griess method
      (nitrite). Treatment of macrophages with rIFN-gamma plus OD (1 mg/ml) caused a
      significant increase in tumor necrosis factor-alpha (TNF-alpha) production
      (4.49+/-1.43 ng/ml) by enzyme-linked immunosorbent assay. The increased
      production of NO and TNF-alpha from rIFN-gamma-plus OD-stimulated cells was
      almost completely inhibited by pretreatment with 100 microM of pyrrolidine
      dithiocarbamate (PDTC), an inhibitor of nuclear factor kappa B (NF-kappaB). PDTC
      also inhibited phosphorylation of IkappaB in rIFN-gamma-plus OD-stimulated cells.
      These findings demonstrate that OD increases the production of NO and TNF-alpha
      by rIFN-gamma-primed macrophages and suggest that NF-kappaB plays a critical role
      in mediating these effects of OD.

PMID- 12230106
TI  - Screening of South American plants against human immunodeficiency virus:
      preliminary fractionation of aqueous extract from Baccharis trinervis.
AB  - Ethanolic and aqueous extracts of 14 South American medicinal plants were tested
      for inhibitory activity on human immunodeficiency virus (HIV). Both extracts were
      relatively non-toxic to human lymphocytic MT-2 cells, but only the aqueous
      extract of Baccharis trinervis exhibited potent anti-HIV activity in an in vitro
      MTT assay. To delineate the extract-sensitive phase, some studies of the
      antiviral properties of the active extract are described in this paper. Based on
      the results presented here, a separation scheme was devised, which permitted the
      preliminary fractionation of the extract, with the aim of finding an inhibitor of
      this virus.

PMID- 12230107
TI  - Antiulcerogenic activity of four extracts obtained from the bark wood of Quassia
      amara L. (Simaroubaceae).
AB  - Quassia amara L., a neotropical forest shrub of the Simaroubaceae family, is
      widely used in Caribbean folk medicine and in some northern states of Brazil for
      the treatment of gastric ulcers. This plant is a source of numerous compounds
      including both beta-carbonile and cantin-6 alkaloids as well as, primarily, the
      bitter compounds known as quassinoids. We analyzed the possible antiulcerogenic
      activities of four extracts of different polarities: 70% ethanol (70% EtOH), 100%
      EtOH, 100% dichloromethane (DCM), and 100% hexane (HEX) obtained from Quassia
      amara bark. All extracts, administered at doses of 5000 mg/kg orally and 1000
      mg/kg intraperitoneally, caused neither toxicity or death. In the
      indomethacin/bethanechol-induced gastric ulcer, 70% EtOH, 100% EtOH, DCM and HEX
      extracts, 100 mg/kg, p.o., inhibited the gastric ulcer (22.5, 23.4, 50.5, 46.8%,
      respectively). 70% EtOH, 100% EtOH, DCM, and HEX extracts reduced the gastric
      injury induced by the hypothermic restraint-stress test in mice (70.7, 80, 60,
      82.7%, respectively). In the pylorus ligature of the mouse stomach, following pre
      treatment with a single intraduodenal administration of 100 mg/kg of each
      extract, only 70% EtOH did not change the biochemical parameters of gastric
      juice. 100% EtOH, DCM and HEX extracts presented decreased gastric juice content,
      increased pH values and decreased acid output. We also determined the
      antiulcerogenic activity on HCl-EtOH-induced gastric ulcers in mice at four doses
      (25, 50, 75, 100 mg/kg, p.o.), then evaluated the possible dose-dependent
      relation and calculated the ED50 values. Except for 70% EtOH at a dose of 25
      mg/kg, the other extracts showed significantly activity (p<0.05). The free mucous
      amount in the gastric stomach content was also evaluated. All extracts showed
      significant increases (p<0.05) of free mucous. This effect was abolished when the
      animals were pre-treated with indomethacin. Prostaglandin synthesis was evaluated
      by the administration of HEX extracts by the oral route (100 mg/kg).
      Prostaglandin synthesis was significantly, increased by 52.3% (p<0.05), and this
      effect was abolished with prior administration of indomethacin. We concluded that
      Quassia amara is a probable source for a new drug to treat gastric ulcers, and
      the mechanism of its activity relates to cytoprotective factors, such as mucous
      and prostaglandins, but there is still the possibility that antisecretory
      activity is involved in its antiulcerogenic effect.

PMID- 12230108
TI  - Enhancing effect of zinc on hepatoprotectivity of epigallocatechin gallate in
      isolated rat hepatocytes.
AB  - The influence of metal ions (Fe2+, Cu2+, Zn2+) on the hepatoprotective activity
      of epigallocatechin gallate (EGCG) against hepatotoxin-induced cell injury was
      investigated. Primary cultures of rat hepatocytes were treated with a well-known
      hepatotoxin, bromobenzene (BB), in the presence of EGCG only or EGCG plus each
      metal ion. After 24 h, 0.02 mM EGCG did not show protective activity on the
      cultured hepatocytes. In contrast, the hepatocytes were protected against BB in
      the presence of 0.02 mM EGCG and 0.02 mM zinc. The addition of only zinc could
      not protect hepatocytes against BB. These results suggest that the formation of
      the zinc-EGCG complex is very important in the enhancement of the
      hepatoprotective activity of EGCG. The complexation of EGCG with zinc was
      confirmed by UV-VIS absorption spectroscopy.

PMID- 12230109
TI  - Effect of chitosan oligosaccharide on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced
      oxidative stress in mice.
AB  - The abilities of two types of chitosan oligosaccharides, chitosan oligosaccharide
      I (1-kDa<MW<3-kDa) and chitosan oligosaccharide II (3-kDa<MW<5-kDa), to prevent
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced oxidative stress were examined
      in ICR mice. Chitosan oligosaccharide I had no effect on TCDD-induced alterations
      in lipid peroxidation and glutathione S-transferase activity or liver weight
      change. However, mice treated with chitosan oligosaccharide II were protected
      from TCDD-induced lipid peroxidation, inhibition of glutathione peroxidase and
      glutathione S-transferase activities, and losses in body and liver weights. These
      results suggest that chitosan oligosaccharide might be a potential agent for
      combating TCDD-induced pathogenesis.

PMID- 12230110
TI  - Expression of cyclooxygenase-2 and pro-inflammatory cytokines induced by
      2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) in human mast cells requires NF-kappa
      B activation.
AB  - Mast cells are critical for initiating innate immune and inflammatory responses
      by releasing a number of pro-inflammatory mediators. The potential
      immunomodulatory properties of hydrogenated aromatic hydrocarbons have been the
      subject of extensive investigation, as the immune system is a sensitive target
      for hydrogenated aromatic hydrocarbon toxicity. In this report, the effects of
      polychlorinated biphenyl (PCB) on the expression of cyclooxygenase-2 and pro
      inflammatory cytokines such as interleukin-1beta (IL-1beta), IL-6 and tumor
      necrosis factor (TNF)-alpha in the human leukemic mast cell line were
      investigated. TNF-alpha and IL-1beta expressed their respective mRNA in the
      presence or absence of PCB, while cyclooxygenase-2 (COX-2) and IL-6 mRNA
      expression were highly induced by PCB after 2 h. Moreover, pre-treatment with the
      nuclear factor (NF)-kappaB pathway inhibitor, pyrrolidine dithiocarbamate,
      suppressed COX-2, TNF-alpha and IL-1beta induction and reduced the IL-6 mRNA
      levels induced by PCB. The NF-kappaB activity was determined by electrophoretic
      mobility shift analysis (EMSA) using an oligonucleotide containing a consensus NF
      kappaB binding sequence. Stimulating the cells with PCB activated NF-kappaB.
      However, pre-treating them with a NF-kappaB pathway inhibitor, pyrrolidine
      dithiocarbamate, suppressed PCB-induced NF-kappaB activation. This suggests that
      PCB induces cycloxoygenase-2 and pro-inflammatory cytokine expression, and that
      this induction occurs through NF-kappaB.

PMID- 12230111
TI  - Suppression of NO production in activated macrophages in vitro and ex vivo by
      neoandrographolide isolated from Andrographis paniculata.
AB  - In this study, we investigated the in vitro and ex vivo suppressive effects of
      Andrographis paniculata on nitric oxide (NO) production in mouse peritoneal
      macrophages elicited by bacillus Calmette-Guein (BCG) and stimulated by
      lipopolysaccharide (LPS). Incubation of BCG-induced macrophages with the methanol
      extract of A. paniculata reduced LPS stimulated NO production. The diterpene
      lactones andrographolide and neoandrographolide were isolated as active
      components from the extract. These compounds suppressed NO production in a
      concentration-dependent manner in the concentration range from 0.1 to 100 microM
      and their IC50 values were 7.9 and 35.5 microM. Neoandrographolide also
      suppressed NO production by 35 and 40% when the macrophages were collected after
      oral administration of neoandrographolide at doses of 5 and 25 mg/kg/d and LPS
      stimulated NO production was examined. However, andrographolide did not reduce NO
      production on oral administration at the same doses. These results indicate that
      neoandrographolide, which inhibited NO production both in vitro and ex vivo may
      play an important role in the use of A. paniculata as an anti-inflammatory crude
      drug.

PMID- 12230112
TI  - Antipruritic and antiinflammatory effects of aqueous extract from Si-Wu-Tang.
AB  - Si-Wu-Tang (SWT), a traditional Chinese formula, has been clinically used in the
      treatment of cutaneous pruritus, chronic inflammation, and other diseases. The
      present study was carried out to observe the antipruritic and antiinflammatory
      effects of SWT aqueous extract using compound 48/80 and picryl chloride (PC)
      models in mice. SWT (500, 1000 mg/kg p.o.) clearly reduced the scratching
      responses elicited by compound 48/80 in normal mice. At doses of 250 and 500
      mg/kg, it inhibited the scratching responses induced by PC in mice actively
      sensitized with 2,4-dinitrophenol (DNP)-ovalbumin (OVA) plus alum. Furthermore,
      SWT (250, 500, 1000 mg/kg) significantly inhibited the footpad swelling caused by
      compound 48/80 in mice. In the biphasic ear skin reactions induced by PC in
      actively sensitized mice, SWT (250, 500 mg/kg) reduced the immediate-phase
      reaction, but did not affect the late-phase reaction. In vitro, SWT (50-500
      microg/ml) showed a concentration-dependent inhibition of the histamine release
      induced by compound 48/80 from rat peritoneal mast cells. The crude drugs
      contained in SWT, Paeoniae Radix (25, 100 microg/ml), Rehmanniae Radix, and
      Chuanxiong Rhizoma (100 microg/ml), also showed a clear inhibition, but Angelica
      Radix did not at the concentrations examined. These findings indicate that SWT
      aqueous extract has antipruritic and antiinflammatory effects in mice. SWT
      inhibits histamine release from rat mast cells, and Paeoniae Radix probably plays
      a crucial role in the formula.

PMID- 12230113
TI  - Antiallergic and anti-inflammatory properties of the ethanolic extract from
      Gleditsia sinensis.
AB  - This study was carried out to determine the effects of the 70% ethanolic extract
      from the anomalous fruits of Gleditsia sinensis LAM. (AFGS) on experimental
      allergic reactions and inflammation. AFGS (200, 500, 1000 mg/kg, p.o.) dose
      dependently inhibited the systemic anaphylactic shock induced by compound 48/80
      in mice and cutaneous reactions induced by histamine or serotonin in rats. At
      doses of 500 and 1000 mg/kg, AFGS showed a clear inhibition on homologous passive
      cutaneous anaphylaxis in rats. In vitro, AFGS significantly reduced histamine
      release from rat peritoneal mast cells triggered by compound 48/80 at
      concentrations of 20 and 50 micro/ml. Moreover, AFGS (500, 1000 mg/kg, p.o.)
      showed a significant inhibition on the hind paw edema in rats and ear swelling in
      mice caused by carrageenin and croton oil, respectively. It also clearly
      inhibited the vascular permeability induced by acetic acid in mice at a dose of
      1000 mg/kg. These findings demonstrate that the ethanolic extract from the
      anomalous fruits of Gleditsia sinensis possesses antiallergic and anti
      inflammatory activities, which may be mediated by reducing the release of
      mediators such as histamine from mast cells and weakening the inflammatory action
      of these mediators.

PMID- 12230114
TI  - Pharmacological evaluation of Shokyo and Kankyo (1).
AB  - Zingiberis Rhizoma (Shokyo, [Japanese characters: see text]) showed significant
      ameliorative effect on the BaCl2-induced delay of gastric emptying in rat.
      Bioassay-guided fractionation of the aqueous extract of Shokyo resulted in
      isolation of 6-gingesulfonic acid (1) and shogasulfonic acid A (3). These
      compounds significantly improved the delay of gastric emptying on both BaCl2
      induced and N(G)-nitro-L-arginine (L-NNA)-induced model in rat. Zingiberis
      Siccatum Rhizoma (Kankyo, [Japanese characters: see text]) had significant
      efficacy against castor oil-induced diarrhea. In addition, Kankyo showed the
      activity increasing intestinal blood flow in normal rat.

PMID- 12230115
TI  - Trypanocidal constituents in plants 1. Evaluation of some Mexican plants for
      their trypanocidal activity and active constituents in Guaco, roots of
      Aristolochia taliscana.
AB  - Crude extracts of Mexican medicinal plants were screened for trypanocidal
      activity against Trypanosoma cruzi, which is the etiological agent for Chagas'
      disease, one of the most serious protozoan diseases in Latin America. There were
      43 kinds of methanolic and other organic extracts from 39 plants which were
      examined by the preliminary screening test to see immobilization of epimastigotes
      of T. cruzi in vitro. Eighteen of them showed activity at the concentration of 2
      mg/ml after incubation for 2 h, while 13 showed activity at the concentration of
      1 mg/ml after incubation for 48 h. Among them, the MeOH extract of roots of
      Aristolochia taliscana (Aristolochiaceae), locally known as "Guaco," immobilized
      all the epimastigotes even at lower concentration of 0.5 mg/ml (48 h). In order
      to identify principal compounds for this activity, the MeOH extract of Guaco was
      subjected to bioassay-guided fractionation. From the active fractions, four
      neolignans, eupomatenoid-7 (1), licarin A (2), eupomatenoid-1 (5) and licarin B
      (6), and two lignans, austrobailignan-7 (3) and fragransin E1 (4) were isolated.
      Compounds 1-4 immobilized all the epimastigotes at the minimum concentration of
      25-75 microg/ml after incubation for 48 h, while compounds 5 and 6 were inactive.
      Corresponding concentration of gossypol, berberine chloride and harmine was 280
      microg/ml, 300 microg/ml and >500 microg/ml, respectively.

PMID- 12230116
TI  - Changes in electrophysiological properties of rat skin with age.
AB  - The age-related changes in the electrical and physiological properties of the
      skin were examined in rats at the ages of 5, 10, 21, 90, and 180 d. The
      resistance of the stratum corneum, the resistance of the viable skin (epidermis
      and dermis), and the capacitance of the stratum corneum were analyzed from skin
      impedance data using an equivalent circuit. With development and aging, the
      resistance of the stratum corneum and the viable skin increased, whereas the
      capacitance of the stratum corneum decreased. Physiological characteristics such
      as the thickness of skin strata and the content of lipid and water in the stratum
      corneum were also measured. The lipid content in the stratum corneum was constant
      at all ages. The water content in the stratum corneum decreased, and the
      thickness of skin strata increased with age. Comparison between electrical data
      and physiological properties suggested that the increase in the resistance of the
      stratum corneum with aging is primarily caused by the decrease in the water
      content and that the capacitance of the stratum corneum and the resistance of the
      viable skin depend on age-related increases in the thickness of skin strata. In
      conclusion, the age dependency of cutaneous electrical properties may affect the
      permeation profile of drugs through the skin, and impedance analysis can be used
      to estimate age-related changes in transdermal drug delivery.

PMID- 12230117
TI  - Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla
      frutescens.
AB  - Oral administration of the perilla leaf extract (PLE) to mice inhibits
      inflammation, allergic response, and tumor necrosis factor-alpha production. We
      also found that PLE suppressed the tumor necrosis factor-alpha (TNF-alpha)
      production in vitro. Using the inhibitory activity of TNF-alpha production in
      vitro as the index for isolation, we searched the active constituents from PLE
      and isolated luteolin, rosmarinic acid and caffeic acid as active components.
      Among the isolated compounds, only luteolin showed in vivo activity: inhibition
      of serum tumor necrosis factor-alpha production, inhibition of arachidonic acid
      induced ear edema, inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced ear
      edema and inhibition of oxazolone-induced allergic edema. These results suggest
      that luteolin is a genuinely active constituent which is accountable for the oral
      effects of perilla.

PMID- 12230118
TI  - Biochemical properties of polysaccharides from black pepper.
AB  - The purified polysaccharides from Piper nigrum were prepared as follows: a hot
      water extract of pepper seeds was fractionated by ultrafiltration with a 5-kDa
      membrane cartridge. A fraction with 5 kDa or bigger molecules was successively
      purified by open column chromatography on DEAE-Toyopearl 650C and Bio-gel P-60
      with each active fraction, resulting in PN-Ib and PN-IIa, purified anti
      complementary polysaccharides. None of the anti-complementary activity of any
      polysaccharide was changed by pronase digestion or polymyxin B treatment, but
      they were decreased by periodate oxidation. Analysis of component sugar and
      molecular mass determination of the anti-complementary polysaccharides indicated
      that PN-Ib with an average molecular mass of 21 kDa contained 88.5% glucose and
      other negligible minor monosaccharides, while PN-IIa showed a different
      monosaccharide composition, which contained a significant proportion of
      galactose, arabinose, galacturonic acid and rhamnose. The molar ratio of
      galactose and arabinose of PN-IIa (48 kDa) was 1.93:1. PN-1 did not react with
      beta-glucosyl Yariv reagent, however, PN-IIa did react, which indicated that PN
      IIa might be an arabinogalactan. Based upon these results, the usefulness of
      purified anti-complementary polysaccharides from Piper nigrum is suggested as a
      supplement for immune enhancement.

PMID- 12230119
TI  - A possible mechanism for the exchange of transferrin-67Ga complex to heparan
      sulfate-67Ga complex.
AB  - We attempted to identify the exchange mechanism of transferrin-67Ga complex to
      heparan sulfate-67Ga complex. The effect of phosphate on the binding ability of
      67Ga to transferrin and heparan sulfate was studied by the dialysis method. The
      phosphate inhibited the binding ability of 67Ga to transferrin, while the
      phosphate enhanced the 67Ga binding ability to heparan sulfate. The results
      suggest that the phosphate is involved in the translocation of 67Ga from the
      transferrin to the heparan sulfate.

PMID- 12230120
TI  - The GCR2 gene is required for the transcriptional activation of retrotransposon
      Ty2-917 in Saccharomyces cerevisiae.
AB  - Ty2 retrotransposons are the mobile genetic elements of the yeast Saccharomyces
      cerevisiae. Transcriptional regulation of Ty2-917 requires a complex set of cis
      acting elements which are located both upstream and downstream of the
      transcription initiation site. Previously, the glycolysis regulatory protein
      Gcr1p has been identified as the major transcriptional regulator of Ty2-917.
      Gcr1p is a DNA binding transcription factor that requires Gcr2p for its
      functions. In this study, the effect of Gcr2p on the transcriptional regulation
      of Ty2-917 was analyzed. The result of this study indicates that Ty2-917
      transcription decreases 24-fold in gcr2 mutant yeast cells. In addition, Ty2
      enhancer element dependent transcriptional activation of a heterolog promoter
      also decreases at a significant level. These results showed that Gcr2p is
      essential for the high level transcription of Ty2-917.

PMID- 12230121
TI  - Regulation of inhibin beta chains and follistatin mRNA levels during rat
      hepatocyte growth induced by the peroxisome proliferator di-n-butyl phthalate.
AB  - Peroxisome proliferators stimulate hepatocyte growth in rat liver in vivo.
      Activin A, a homodimer of inhibin betaA, inhibits DNA synthesis in hepatocytes.
      The inhibitory action of activin A is suppressed by follistatin, an activin
      binding protein. In this paper, we investigated whether administration of di-n
      butyl phthalate (DBP), a peroxisome proliferator, modifies the production of
      activin A and follistatin in rat liver by hourly monitoring of inhibin betaA and
      follistatin mRNA levels by reverse transcriptase polymerase chain reaction
      analysis. The mRNA levels of the other inhibin beta chains (inhibin betaB and
      betaC) were examined in a similar manner. The inhibin betaA mRNA level decreased
      to about 30% by 3 h after DBP administration (8.6 mmol/kg body weight), remained
      low until 12 h, and returned to its original level by 24 h. The follistatin mRNA
      level increased to about 2 times by 6 h, and returned to its original level by 24
      h. The inhibin betaB mRNA had started to increase by 1 h, peaked at 6 h at about
      4 times its initial level, and returned to its original level by 12 h. The
      inhibin betaC mRNA level had doubled by 6 h and it returned to its original
      level. These results indicate that the growth stimulatory action of peroxisome
      proliferators may be mediated via the decrease in activin A level and activity
      and suggest that the increases in follistatin as well as inhibin betaB and betaC
      chains may play a role in peroxisome proliferator-stimulated hepatocyte growth.

PMID- 12230122
TI  - Chemokine receptor CXCR2 activates distinct pathways for chemotaxis and calcium
      mobilization.
AB  - Rat cytokine-induced neutrophil chemoattractant-3 (CINC-3) has neutrophil
      chemotactic activity comparable with that of CINC-1 and CINC-2, but induces
      calcium mobilization more potently than CINC-1 and CINC-2. However, only one CINC
      receptor, CXCR2, has been found in rat neutrophils. Therefore we attempted to
      determine the biochemical basis for the differences in neutrophil responses to
      CINC-1/-2 versus CINC-3. Both chemotactic activity and calcium mobilization
      induced by CINC-3 were desensitized by a 100-fold excess of CINC-1, which was
      consistent with our previous results showing that CINC-1 has 70-fold lower
      affinity to the receptor on rat neutrophils than CINC-3. Desensitization appeares
      to be reflected by the affinity of the ligands to the receptor. CINC-1- and CINC
      3-induced chemotaxis was sensitive to inhibition by pertussis toxin, whereas
      calcium mobilization induced by CINC-1 and CINC-3 was insensitive. These results
      suggest that CINCs induce neutrophil chemotaxis and calcium mobilization through
      distinct G-proteins with different efficiency.

PMID- 12230123
TI  - Inhibition of 3 alpha/beta,20 beta-hydroxysteroid dehydrogenase by dexamethasone,
      glycyrrhetinic acid and spironolactone is attenuated by deletion of 12 carboxyl
      terminal residues.
AB  - We constructed a pig 3alpha/beta,20beta-hydroxysteroid dehydrogenase
      (3alpha/beta,20beta-HSD) mutant, which lacks 12 carboxyl-terminal amino acids
      residues. Enzyme activity studies indicated that the deleted amino acids have a
      role in steroid metabolism and may assist in substrate binding in wild-type
      3alpha/beta,20beta-HSD. Furthermore, substrate binding likely induces a
      conformational change allowing the 12 carboxyl-terminal amino acids interact with
      the steroid substrate [Nakajin S. et al., Biochim. Biophys. Acta, 1550, 175-182
      (2001)]. In this paper, we clarified that although pig 3alpha/beta,20beta-HSD is
      potently inhibited by dexamethasone, glycyrrhetinic acid and spironolactone, this
      inhibition is remarkably attenuated by deleting the 12 carboxyl-terminal
      residues. The inhibition constant (Ki) of pig 3alpha/beta,20beta-HSD for
      dexamethasone increased 115-fold. These observations also indicate that these
      amino acid residues interact with steroid substrates or steroid inhibitors and
      have an important role in substrate or inhibitor binding to the active site.

PMID- 12230124
TI  - An antiprogesterone, onapristone, enhances the gene expression of promatrix
      metalloproteinase 3/prostromelysin-1 in the uterine cervix of pregnant rabbit.
AB  - Using a progesterone receptor antagonist, onapristone/ZK 98.299, we examined the
      in-vivo effects of progesterone on the function of uterine cervix during
      pregnancy. Onapristone was intravenously administered to pregnant rabbits on day
      20 post coitum. After 24 h, the antiprogesterone increased the wet weight of the
      uterine cervix and decreased the DNA concentration in the cervix. In-situ
      hybridization also indicated that antiprogesterone augmented the expression of
      matrix metalloproteinase (MMP)-3/stromelysin-1 mRNA in the uterine cervix. These
      changes are very similar to those observed and reported thus far in ripened and
      dilated uterine cervix. These results suggest that during pregnancy, progesterone
      closely participates in the maintenance of the function of uterine cervix by
      preventing the production of MMPs and thereby destruction of extracellular
      matrix, and thus add support to the theory that antiprogesterone has the
      potential to accelerate for the uterine cervical ripening and dilatation.

PMID- 12230125
TI  - Absorption of Val-Tyr with in vitro angiotensin I-converting enzyme inhibitory
      activity into the circulating blood system of mild hypertensive subjects.
AB  - The change in plasma level of dipeptide, Val-Tyr (VY), with in vitro angiotensin
      I-converting enzyme inhibitory activity was investigated after a single oral
      administration of a VY-drink at doses of 0, 6 or 12 mg given to mild hypertensive
      subjects. During this protocol for up to 24 h after the intake, patient/subject
      blood pressure (BP) was measured for a 15 min period at designated times (0, 1,
      2, 4, 8, 24 h) with the individual supine. Based on the VY determination, the
      maximal increment of plasma VY level was observed over the second hour
      postprandially (12 mg-dose; 2041+/-148 fmol/ml-plasma). In addition, the plasma
      VY level increased with the VY dosage. However, no marked BP change was observed
      with the increase of plasma VY level, suggesting that VY did not exert an acute
      hypotensive effect. The area under the curve at 12 mg-dose was estimated to be
      8644+/-420 fmol x h/ml-plasma, comparable to that in normotensive subjects. This
      finding suggests that absorption of VY would not be influenced by a complaint of
      hypertension.

PMID- 12230126
TI  - Taurine treatment reduces hepatic lipids and oxidative stress in chronically
      ethanol-treated rats.
AB  - In this study, we evaluated whether taurine treatment has a protective effect on
      the prooxidant-antioxidant state following chronic ethanol treatment in rats.
      Rats were given water containing 20% ethanol (v/v) as drinking water for 3
      months. Chronic ethanol treatment in drinking water resulted in increased
      oxidative stress in the liver of rats. Taurine treatment was performed by adding
      1% taurine (w/v) to the drinking water plus injection (400 mg/kg body weight)
      intraperitoneally 3 times/week for 28 d after ethanol cessation in chronically
      ethanol-treatad rats. This treatment starting after ethanol cessation caused a
      significant decreases in serum transaminase activities and hepatic total lipid,
      triglyceride, malondialdehyde, and diene conjugate levels and significant
      increases in hepatic glutathione, vitamin E, and vitamin C levels, but did not
      alter the activities of superoxide dismutase, glutathione peroxidase, and
      glutathione transferase in the liver as compared with chronically ethanol-treated
      rats. Accordingly, we propose that taurine has a restorative effect on ethanol
      induced hepatic damage by decreasing oxidative stress.

PMID- 12230127
TI  - Antidiabetic activity of Lyophyllum decastes in genetically type 2 diabetic mice.
AB  - The antidiabetic activity of Lyophyllum decastes (Tricholomataceae) was
      investigated in KK-Ay mice, an animal model of genetically type 2 diabetes with
      hyperinsulinemia. The water extract of Lyophyllum decastes (LD) (500 mg/kg body
      weight) reduced the blood glucose of KK-Ay mice 7 h after a single oral
      administration (p<0.05) when compared with control. LD reduced the blood glucose
      of KK-Ay mice 3 weeks after repeated administration (p<0.05), and also
      significantly lowered the serum insulin of KK-Ay mice under similar conditions
      (p<0.01). However, LD did not affect the blood glucose in normal mice. LD tended
      to decrease of the blood glucose in an insulin tolerance test. In addition, the
      muscle content of facilitative glucose transporter isoform 4 (GLUT4) protein
      content in the plasma membrane fraction from muscle significantly increased in
      the orally LD-treated KK-Ay mice when compared to that of the controls (p<0.01).
      These results suggest that the antidiabetic activity of LD is derived, at least
      in part, from a decrease in insulin resistance, due to the increase of GLUT4
      protein content in the plasma membrane of the muscle.

PMID- 12230128
TI  - Activity-guided fractionation of green tea extract with antiproliferative
      activity against human stomach cancer cells.
AB  - Epidemiological studies have suggested that the consumption of green tea provides
      protection against stomach cancer. Fractionation of green tea extract, guided by
      antiproliferative activity against human stomach cancer (MK-1) cells, has
      resulted in the isolation of six active flavan-3-ols, epicatechin (EC),
      epigallocatechin (EGC), epigallocatechin gallate (EGCg), gallocatechin (GC),
      epicatechin gallate (ECg), gallocatechin gallate (GCg), together with inactive
      glycosides of kaempferol and quercetin. Among the six active flavan-3-ols, EGCg
      and GCg showed the highest activity, EGC, GC, ECg followed next, and the activity
      of EC was lowest. These data suggest that the presence of the three adjacent
      hydroxyl groups (pyrogallol or galloyl group) in the molecule would be a key
      factor for enhancing the activity. Since reactive oxygen species play an
      important role in cell death induction, radical scavenging activity was evaluated
      using the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical. The order of scavenging
      activity was ECg > or = EGCg > or = EGC > or = GC > or = EC. The compounds having
      a galloyl moiety showed more potent activity. The contribution of the pyrogallol
      moiety in the B-ring to the scavenging activity seemed to be less than that of
      the galloyl moiety.

PMID- 12230129
TI  - Antitumor-promoting constituents from Dioscorea bulbifera L. in JB6 mouse
      epidermal cells.
AB  - An antitumor-promoting effect was found in the extracts/ingredients of a plant
      used as a traditional medicine in mainland China, using the neoplastic
      transformation assay of mouse epidermal JB6 cell lines. The ethyl acetate soluble
      fraction of 75% ethanol extract of the rhizomes of Dioscorea bulbifera L. showed
      an inhibitory effect against the tumor promotion of JB6 (Cl 22 and Cl 41) cells
      induced by a promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Further
      investigation on the constituents of the EtOAc fraction from the rhizomes
      revealed the chemical structure to be kaempferol-3,5-dimethyl ether (1), caryatin
      (2), (+)-catechin (3), myricetin (4), quercetin-3-O-galactopyranoside (5),
      myricetin-3-O-galactopyranoside (6), myricetin-3-O-glucopyranoside (7) and
      diosbulbin B (8). Constituent antitumor-promoting activities were also examined
      in the same way. Compounds 1-7, characterized as flavonoids with the two hydroxyl
      groups at C-7 and C-4', showed the most potent inhibitory effect, but there
      seemed to be differences in the inhibitory effect between flavonol aglycones and
      flavonol glycosides. Compared with (-)-epicatechin, (+)-catechin exhibited much
      stronger inhibitory activity which suggested that chemical stereo structures of
      compounds affect the efficiency of inhibition. Compound 8 showed moderate
      activity. The constituents with antitumor-promoting activity from this plant are
      reported for the first time.

PMID- 12230131
TI  - Antihypertensive effect of sesamin. IV. Inhibition of vascular superoxide
      production by sesamin.
AB  - We previously demonstrated the preventive effect of sesamin, a lignan from sesame
      oil, on the development of several experimental models of hypertension. In the
      present study, we explored the mechanisms underlying the antihypertensive effect
      of sesamin using the deoxycorticosterone acetate (DOCA)-salt rat hypertensive
      model. After a 5-week treatment period, aortic superoxide (O2-) production was
      measured in the lucigenin chemiluminescence assay. Chemiluminescence signals
      significantly decreased in sesamin-containing diet-fed DOCA-salt hypertensive
      rats compared with those in the normal diet-fed DOCA-salt rats, although the
      signals in sham-operated control animals were not affected by the sesamin
      feeding. In addition, there was a positive correlation between systolic blood
      pressure and aortic O2- production. These findings suggest that sesamin feeding
      inhibits enhanced vascular O2- production in DOCA-salt hypertensive rats and that
      the antioxidative action of sesamin may contribute to its antihypertensive
      activity.

PMID- 12230130
TI  - Successful treatment of severe hyperammonemia using sodium phenylacetate powder
      prepared in hospital pharmacy.
AB  - In order to treat a hyperammonemic patient with adult-onset type-II citrullinemia
      (CTLN2), sodium phenylacetate powder was prepared from chemical reagent grade
      phenylacetic acid in Gunma University Hospital. After purification by
      recrystalization, phenylacetic acid was neutralized with sodium carbonate and
      dried at 70 degrees C under reduced pressure. A solution of the prepared powder
      produced a single peak of m/z=181.0 (M+Na+) in electrospray-ionization-MS
      spectrogram. The content of phenylacetate was 74% of theoretical value,
      suggesting the existence of water of crystallization. The content of
      phenylacetate remained constant for 5 months under dark conditions at room
      temperature. The prepared sodium phenylacetate powder was orally administered to
      a 16-year-old patient with CTLN2 at a dosage of 12 g/d. The serum ammonia
      concentration of the patient, who did not show adequate response to intravenous
      arginine or oral sodium benzoic acid decreased remarkably to less than 100
      microg/dl. Sodium phenylacetate powder should be an essential drug for the
      treatment of hyperammonemia caused by an inborn error of the urea cycle.

PMID- 12230132
TI  - Uptake and distribution of 137Cs and 90Sr in salix viminalis plants.
AB  - Agricultural areas in middle and northern parts of Sweden were contaminated with
      radionuclides after the Chernobyl accident in 1986. Alternative crops in these
      areas are biomass plantations with fast-growing Salix clones for energy purposes.
      The uptake and internal distribution of 137Cs and 90Sr in Salix viminalis were
      studied. Plants were grown in microplots under field conditions. The soils in the
      experimental site had been contaminated in 1961 with 35.7 and 13.4 MBq m(-2) of
      137Cs and 90Sr, respectively. The experiment was carried out during three years.
      The plots were fertilised with 60 kg N ha(-1) and three treatments of K,
      consisting of 0, 80 and 240 kg K ha(-1) during the first two years. The activity
      concentration of 137Cs in the different plant parts varied between 140 and 20,000
      Bq kg(-1) and was ranked in the following order: lowest in stems < cuttings <
      leaves < roots. The fine roots (0-1 mm) had the highest 137Cs activity
      concentration. One-year-old stems had higher 137Cs activity concentrations than
      two-year-old stems. The activity concentration of 137Cs in the plants was
      significantly affected by K-supply and was higher in the 0 kg K treatment than in
      the 80 or 240kg K treatment. Leaves contained more 90Sr than stems and cuttings.

PMID- 12230133
TI  - Study of a predictive methodology for quantification and mapping of the radon-222
      exhalation rate.
AB  - We propose a new methodology for predicting areas with a strong potential for
      radon (222Rn) exhalation at the soil surface. This methodology is based on the Rn
      exhalation rate quantification, starting from a precise characterisation of the
      main local geological and pedological parameters that control the radon source
      and its transport to the soil/atmosphere interface. It combines a cross mapping
      analysis of these parameters into a geographic information system with a model of
      the Rn vertical transport by diffusion in the soil. The rock and soil chemical
      and physical properties define the entry parameters of this code (named TRACHGEO)
      which calculates the radon flux density at the surface. This methodology is
      validated from in situ measurements of radon levels at the soil/atmosphere
      interface and in dwellings. We apply this approach to an area located in western
      France and characterised by a basement displaying a heterogeneous radon source
      potential, as previously demonstrated by lelsch et al. (J. Environ. Radioactivity
      53(1) (2001) 75). The new results obtained show that spatial heterogeneity of
      pedological characteristics in addition to basement geochemistry--must be taken
      into account to improve the mapping resolution. The TRACHGEO forecasts explain
      the Rn exhalation variability on a larger scale and in general correlate well
      with in situ observations. Moreover, the radon-prone sectors identified by this
      approach generally correspond to the location of the dwellings showing the
      highest radon concentrations.

PMID- 12230134
TI  - Predictions of in situ solid/liquid distribution of radiocaesium in soils.
AB  - Previous work has demonstrated that plant uptake of radiocaesium (RCs) is related
      to the activity concentration of RCs in soil solution, which is linked to the
      soil/soil solution distribution coefficient, K(D). The solid-liquid distribution
      of RCs is generally studied in soil suspensions in the laboratory and there are
      few reported measurements for in situ soil solutions. From a data set of 53
      different soils (contaminated with either 134CsCl or 137CsCl) used in pot trials
      to investigate grass uptake of RCs, we analysed the variation of in situ K(D)
      with measured soil properties. The soils differed widely in % clay (0.5-58%),
      organic matter content (1.9-96%) and pH (2.4-7.0, CaCl2). The K(D) varied between
      29 and 375,000 L kg-' (median 1460 L kg(-1)). Stepwise multiple regression
      analysis showed a significant correlation between the log K(D) and pH (p <
      0.001), log %clay (p < 0.01) and log exchangeable K (p < 0.001) (overall R2 =
      0.70). The in situ K(D) values were further compared to K(D)S predicted using an
      existing model, which assumes that RCs sorption occurs on specific sites and
      regular ion-exchange sites on the soil solid phase. Sorption of RCs on specific
      sites was quantified from the radiocaesium interception potential (RIP) measured
      for each soil and the soil solution concentrations of K+ and NH4+. The in situ
      log K(D) correlated well with the predicted K(D) (R2 = 0.85 before plant growth,
      R2 = 0.83 after plant growth). However, the observations were fivefold to
      eightfold higher than the predictions, particularly for the mineral soils. We
      attribute the under-prediction to the long contact times (minimum 4 weeks)
      between the RCs tracers and our experimental soils relative to the short (24 h)
      contact times used in RIP measurements. We conclude that our data confirmed the
      model but that ageing of RCs in soil is a factor that needs to be considered to
      better predict in situ KD values.

PMID- 12230135
TI  - Evaluation of the effect of a cover layer on radon exhalation from uranium mill
      tailings: transient radon flux analysis.
AB  - An experimental study concerning the transport of 222Rn in uranium mill tailings
      (UMTs) and in the cover layer was launched in 1997 with the participation of the
      French uranium mining company (COGEMA). Evaluation of the cover layer's
      effectiveness in reducing 222Rn flux emanating from UMTs was one of its
      objectives. In the first phase, the 222Rn flux densities were measured regularly
      on a UMT layer. In the second phase, the UMT was covered with a one-meter layer
      of compacted material consisting of crushed waste rock derived from mining
      activities. Radon-222 flux was then measured at the surface of this cover layer.
      Observations were compared with radon flux calculated using TRACI, a model for
      vertical water and gas flow and radon transport. The results show that the
      calculations bear a fair resemblance to the observations in both cases. They also
      show that the effectiveness of the cover layer calculated with TRACI, using the
      thickness and textural properties of the cover material, is very close to the
      measured effectiveness.

PMID- 12230136
TI  - The influence of urbanization on natural radiation levels in anomalous areas.
AB  - This paper verifies the effects of urbanization on the original levels of
      environmental gamma radiation in an anomalous area. The fieldwork was done in the
      city of Guarapari, on the seacoast of the state of Espirito Santo, Brazil. This
      place was chosen because the whole region is naturally rich in monazite sand,
      which contains thorium and uranium. A similar study was also carried out in the
      1960s. The measurements were done using an inorganic NaI scintillometer detector
      with Cu+Pb filters coupled to a scaler. The methodology of measurements used was
      similar to the one applied in the fieldwork carried out in the 1960s. In
      addition, a simulation was performed in the laboratory, to determine the
      attenuation of the materials used in the urbanization of the region. The results
      of this work clearly show that there was a reduction in the levels of external
      radiation in the streets and squares of Guarapari. It was concluded that the
      reduction was due to attenuation by the materials used in the urbanization.

PMID- 12230137
TI  - A simple method for the estimation of the bioavailability of radiocaesium from
      herbage contaminated by adherent soil.
AB  - Adherent soil may contribute a large proportion of the radiocaesium content of
      sampled vegetation. Consequently, inadvertent ingestion of adherent soil can
      contribute significantly to the radiocaesium intake of grazing animals, and needs
      to be accounted for within radiological assessments. However, accurate estimation
      of the degree of soil adhesion on vegetation is acknowledged to be difficult. To
      determine the relative contributions of vegetation and soil to the radiocaesium
      contamination of milk and tissues, soil-specific estimation of radiocaesium
      bioavailability values would be required. Here we suggest that a previously
      developed in-vitro bioavailability assay (involving a 2 h extraction with 0.1 M
      stable CsCl) can be used to estimate the true absorption coefficient of
      radiocaesium associated with sampled vegetation directly. Using this technique,
      seasonal trends in bioavailability are demonstrated to vary in accordance with
      estimations of the degree of soil adherent to vegetation collected from an upland
      pasture. The use of this technique would negate the need for detailed
      measurements of the amount of soil adhering to sampled vegetation and soil
      specific radiocaesium bioavailability assessments.

PMID- 12230138
TI  - Quantifying 137Cs aggregated transfer coefficients in a semi-natural woodland
      ecosystem adjacent to a nuclear reprocessing facility.
AB  - Radiocaesium (137Cs) activity concentrations and aggregated transfer factors (Tag
      values) were calculated for vascular plants, fungal fruiting bodies and
      invertebrates in a semi-natural Picea sitchensis woodland (Lady Wood) adjacent to
      the British Nuclear Fuels plc. reprocessing facility at Sellafield, Cumbria, UK.
      The Tag values for vascular plants ranged from 7.1 x 10(-4) - 1.9 x 10(-2) m2 kg(
      1), the maximum value being for Pteridium aquilinum. Fungal fruiting bodies had
      higher Tag values (1.9 x 10(-3) - 1.8 x 10(-1) m2 kg(-1)) than vascular plants,
      with a maximum value for Mycena galericulata. None of the activity concentrations
      for edible foodstuffs collected within this study (fungi and berries) exceeded
      the EC recommended limits of 137Cs in foodstuffs grown within the UK. The
      invertebrate community sampled during the study had Tag values ranging from 3.4 x
      10(-4) to 1.3 x 10(-2) m2 kg(-1). There were no systematic differences in 137Cs
      activity concentration between invertebrate guilds, or between seasonal cohorts
      within guilds. The invertebrates in Lady Wood were exposed to a dose from 137Cs
      (internal gamma + beta and external gamma) ranging between 4.37 x 10(-4) and 6.40
      x 10(-4) mGy day(-1). Including dose from radionuclides other than 137Cs and
      accounting for uncertainties due to the relative biological effectiveness of
      differing radionuclides could increase total dose by approximately an order of
      magnitude. These dose rates are at least three orders of magnitude lower than the
      1 mGy d(-1) level at which harm may be caused to terrestrial biota, hence the
      risk to the invertebrate community from the effects of ionising radiation in Lady
      Wood is low.

PMID- 12230139
TI  - Influences of current mood and noise sensitivity on judgments of noise annoyance.
AB  - Noise annoyance is one of the most studied reactions to auditory events. Previous
      research has demonstrated that annoyance reactions may be mediated by individual
      characteristics such as personality, attitudes, and noise sensitivity (traits).
      Transient temporary states such as an individual's current mood have been studied
      to a lesser extent. The author studied annoyance reactions to an everyday noise
      in participants who either were slightly annoyed or in a neutral affective state.
      The results showed that current mood had an overall effect on judgments of
      annoyance and on a participant's preference for sound. In addition, a
      participant's current mood interacted with noise sensitivity. These results
      indicate that both individual noise sensitivity (traits) and transient moods
      (states) are important for human auditory perception and evaluation.

PMID- 12230140
TI  - Contact and the personal/group discrimination discrepancy in an Inuit community.
AB  - The personal/group discrimination discrepancy involves disadvantaged group
      members rating discrimination directed at their group considerably higher than
      ratings of discrimination aimed at themselves personally as members of that
      group. This robust phenomenon has been found in samples of women, African
      Americans, and aboriginal people. In the present study, the authors used a sample
      of Inuit from a remote Arctic community to confirm the perceived discrepancy.
      However, ratings for perceived group discrimination were surprisingly low. The
      authors argue that geographical isolation may have led Inuit to be unaware of the
      impact of discrimination on their lives. In support of this argument, findings
      showed that group discrimination ratings were higher for Inuit who did have
      contact with mainstream Canadian culture. Implications for the traditional
      contact hypothesis are discussed.

PMID- 12230141
TI  - Field study investigation of applicant use of influence tactics in a selection
      interview.
AB  - Employees often evaluate leadership potential when selecting applicants for jobs
      that require leadership ability (e.g., supervisors, firefighter captains).
      Research has shown that influencing others is an important part of being an
      effective leader, yet employers rarely explicitly consider applicants' use of
      influence tactics when evaluating applicants' leadership potential. The purpose
      of this study was to explore applicant use of influence tactics in an employment
      interview and to determine how such use relates to interview ratings. The authors
      observed firefighter applicants' behavior during a selection role-play interview
      and recorded their use of influence tactics. Results indicated that firefighter
      applicants used soft tactics (e.g., ingratiation, rational persuasion)
      significantly more frequently than they used hard tactics (e.g., pressure,
      coalition). Soft tactic use was positively correlated with interview ratings.

PMID- 12230142
TI  - A comparison of four causal factors of embarrassment in public and private
      situations.
AB  - In this study the authors investigated which of 4 causal factors of embarrassment
      is most characteristic in public and in private situations. University students
      (N = 288) were presented with 2 scenes representing public or private situations
      and were asked to rate 17 items related to the 4 factors causing embarrassment.
      The results indicated that in the public situation the causal factors were
      ordered as (a) disruption of social interaction, (b) apprehension of social
      evaluation, (c) inconsistency with self-image, and (d) loss of self-esteem, and
      in the private situation causal factors were ordered as (a) loss of self-esteem,
      (b) inconsistency with self-image, (c) apprehension of social evaluation, and (d)
      disruption of social interaction. From these results, new models for the
      mediating mechanism of embarrassment are proposed.

PMID- 12230143
TI  - Moderating factors explaining stress reactions: comparing chronic-without-acute
      stress and chronic-with-acute-stress situations.
AB  - The author compared patterns of moderating factors explaining stress reactions
      during 2 states: chronic-without-acute-stress and chronic-with-acute-stress. She
      hypothesized that personal dispositions would contribute more to understanding
      stress reactions during a prolonged stress state than during an acute state. The
      participants were Israeli Jewish adolescents living in West Bank settlements
      during the prolonged (chronic-without-acute-stress) state of the intifada (the
      Palestinian uprising against Israeli occupation) and during the chronic-with
      acute-stress state, immediately after the assassination of Prime Minister Rabin.
      The author examined 5 variables as moderating factors--trait anxiety, sense of
      coherence, cognitive appraisal of the political situation, family sense of
      coherence, and sense of community--and measured 2 stress reactions--state anxiety
      and psychological distress. Data were collected from 266 8th-grade students
      during the chronic-without-acute-stress state and 448 students at the same grade
      level at the chronic-with-acute-stress state. The overall magnitude of variance
      explanation was different at each state: The author found a relatively high
      explained variance of state anxiety and psychological distress in the chronic
      without-acute-stress situation but not in the chronic-with-acute stress state.
      These data support the value of developing a model that would recognize the
      different types of stress situations for moderating the effects of stress.

PMID- 12230144
TI  - Self-monitoring and future time orientation in romantic relationships.
AB  - The author examined the relationship between self-monitoring and participant's
      gender, and future time orientation in romantic relationships (FrORR) and tested
      the concurrent validity of the FTORR scale in this respect. One hundred seventy
      three undergraduate students from Middle East Technical University were given M.
      Snyder's (1974) self-monitoring scale and B. Oner's (2000b) FTORR scale. Low self
      monitoring participants had a more extended future time orientation (FTO) than
      high self-monitoring participants in terms of romantic associations.

PMID- 12230145
TI  - An evaluation of a perceived overqualification scale across work settings.
AB  - The authors extended and evaluated the dimensionality of the L. J. Khan and P. C.
      Morrow (1991) subjective underemployment scale. They used data from 3 independent
      samples to assess the measurement properties of the scale. The results of
      confirmatory factor analyses supported 2 dimensions and indicated that the
      measurement model parameters partially generalized across samples. Correlational
      and additional confirmatory factor analytic results rendered empirical support
      for most of the postulated relationships of the 2 overqualification dimensions
      with the somatization, job satisfaction, and organizational commitment variables.
      The findings indicate that the scale of perceived overqualification needs to be
      further developed and validated in different samples. The implications of the
      findings for person-job fit are discussed.

PMID- 12230146
TI  - Symbols presentation modality as a determinant of gambling behavior.
AB  - In this study, the authors investigated the effects that modality of symbol
      presentation on video lottery terminals (sequential vs. simultaneous) has on
      gambling behavior. They predicted that sequential presentation would incite
      players to prolong their gambling session. Results confirmed this prediction and
      showed that modality of presentation is a determinant of gambling persistency.
      The authors discuss the relationship between modality of presentation, hopes of
      an imminent win, losses, and practical and theoretical issues about other
      cognitive and emotional elements that may influence gamblers' behaviors.

PMID- 12230147
TI  - Ethical considerations for research and treatment with runaway and homeless
      adolescents.
AB  - Ethical considerations for working with runaway and homeless youth in research
      and treatment settings are presented. Issues of parents' and adolescents' consent
      for research and treatment are discussed, with particular attention given to the
      lack of explicit guidelines for working with abused and neglected youth. The
      principles of beneficence and justice are discussed as they apply to intervening
      with a high-risk, multiproblem population. The authors offer a rationale for
      allowing adolescents to self-consent to research and treatment. They argue that
      in many circumstances, requiring parental consent may not be in the youth's best
      interest and may preclude his or her participation in treatment and research
      programs.

PMID- 12230148
TI  - Visual habituation at five months: short-term reliability of measures obtained
      with a new polynomial regression criterion.
AB  - Using a new polynomial regression criterion, the authors investigated empirically
      the short-term reliability of infants' visual habituation measures. Twenty-one 5
      month-old infants were tested twice with a 1-day interval. Results revealed many
      reliable habituation measures, a reliable reaction to novelty measure, and a new
      reliable measure of interest. The 2nd-order polynomial regression criterion
      probably produced this improvement because it uses all of the available looking
      time data.

PMID- 12230149
TI  - Improving children's mental rotation accuracy with computer game playing.
AB  - The authors investigated the relation between mental rotation (MR) and computer
      game-playing experience. Third grade boys (n = 24) and girls (n = 23) completed a
      2-dimensional MR test before and after playing computer games (during 11 separate
      30-min sessions), which either involved the use of MR skills (the experimental
      group) or did not involve the use of MR skills (the control group). The
      experimental group outperformed the control group on the MR posttest but not on
      the pretest. Boys outperformed girls on the pretest but not on the posttest.
      Children whose initial MR performance was low improved after playing computer
      games that entailed MR skills. The findings imply that computer-based
      instructional activities can be used in schools to enhance children's spatial
      abilities.

PMID- 12230150
TI  - The importance of social context in cross-cultural comparisons: first graders in
      Colombia and the United States.
AB  - The authors explored the cultural constructs of individualism and collectivism by
      investigating the prosocial behavior of 1st graders (N = 202; 110 girls, 92 boys)
      in countries typically classified as collectivist (Colombia, South America) and
      individualist (United States). Contrary to expectations, U.S. children shared
      more than Colombian children did. However, U.S. children were more likely to take
      candy from another child without permission (demonstrating individualism).
      Results indicated that in both countries sharing was greater with friends than
      with other fellow classmates, and children frequently reported friendship as the
      reason they shared. Findings support the importance of the social context, such
      as the relationship between participants, in cross-cultural research and suggest
      that simple dichotomies of culture often overlook complex associations between
      culture and behavioral differences.

PMID- 12230151
TI  - Worry and sleep length revisited: worry, sleep length, and sleep disturbance
      ascribed to worry.
AB  - The author administered university students (N = 222; 152 women, 70 men) the
      Worry Domains Questionnaire (F. Tallis, G. C. L. Davey, & A. Bond, 1994) and a
      newly constructed scale (the Sleep Disturbance Ascribed to Worry Scale) to
      measure sleep disturbance attributed to worry. To revisit previous studies (i.e.,
      E. Hartmann, F. Baekeland, & G. R. Zwilling, 1972; S. J. H. McCann & L. L.
      Stewin, 1988) that suggested that sleep length was positively related to worry,
      the author also asked the students a question about habitual sleep length. The
      results indicated that worry and sleep disturbance attributed to worry were
      negatively related to sleep length. A regression analysis revealed that worry was
      significantly negatively related to habitual sleep length irrespective of sleep
      disturbance ascribed to worry.

PMID- 12230152
TI  - Narrative discourse and theory of mind development.
AB  - The authors examined experimentally whether exposure to social discourse about
      concepts related to mental states could promote changes in children's theory of
      mind understanding. In 2 studies, 3- to 4-year-old children were assigned to
      either a training or a no training control condition. All children were
      administered several theory of mind measures at pretest and 2 posttests. Training
      was not effective in improving performance in Study 1 (n = 37); but in Study 2 (n
      = 54), modifications of the training procedure led to significant improvements on
      measures of false belief and deception from pretest to 1st posttest. The findings
      support the influence of social discourse on children's theory of mind
      development.

PMID- 12230153
TI  - Verbal and nonverbal interactions of four- and five-year-old friends in potential
      conflict situations.
AB  - Dyads of 4- and 5-year-old friends and nonfriends attending preschools in central
      Italy were identified by friendship nominations. The 217 dyads of friends and non
      friends participated in 2 closed-field tasks designed to simulate real-life
      situations of potential conflict. In the 4-year-old cohort, there were no
      significant differences in the behavior of the partners in either of the
      situations. However, at age 5 years, friends respected the rules of a fast-paced
      competitive game significantly more than did nonfriends. In discussing how to
      share a single object (a chocolate egg with a toy inside), 5-year-old friends
      were more likely to reach agreement than were nonfriends. The results suggest
      important developmental changes in the processes of negotiation and sharing
      within the preschool years.

PMID- 12230154
TI  - Preschoolers' inhibition in their home: relation to temperament.
AB  - Researchers assessed 58 preschoolers' reactions to an unfamiliar person and
      unfamiliar objects in their familiar home environment. Children participated in a
      30-min procedure designed to elicit behavioral inhibition, including (a) a free
      play period with a stranger present, (b) a structured interaction with the
      stranger, and (c) uncertainty-eliciting tasks. Behaviors representing the child's
      reactions toward the mother, stranger, and novel objects were coded. Mothers
      completed a temperament scale. Preschoolers exhibited behaviors indicative of
      inhibition toward unfamiliar social and nonsocial stimuli; behaviors remained
      stable across increasingly intrusive episodes. The approach/withdrawal component
      of temperament was related to behavioral inhibition. Individual differences in
      mood did not appear to be related to differences in inhibition. Parent reported
      temperament was related to researcher-observed behaviors.

PMID- 12230155
TI  - Age differences in coping resources and satisfaction with life among middle-aged,
      young-old, and oldest-old adults.
AB  - The authors examined age differences in perceived coping resources and
      satisfaction with life across 3 older-adult age groups (45-64, 65-74, and 75
      years and older). The 98 participants represented healthy, socially active,
      community-residing adults. Group comparisons were made on 12 individual coping
      scales, and an overall coping resource effectiveness score was computed. No
      significant differences were found for 11 of the coping resources or for overall
      coping resource effectiveness. Similar consistencies in life satisfaction were
      found across the 3 age groups. The findings indicate that (a) for healthy adults,
      the oldest old cope at least as effectively as their younger counterparts,
      despite their likelihood of encountering increased levels of stress; and (b)
      psychologically, old age may be viewed as a time of resilience and fortitude.

PMID- 12230156
TI  - Environmental and individual influences on Australian students' likelihood of
      staying in school.
AB  - In this longitudinal study, the author examined environmental and individual
      influences on the likelihood of Australian adolescents staying in school.
      Participants were 6,778 Anglo Australian, 350 Asian, and 472 European students
      (mean age = 14.7 years) who were in Year 9 when the study began. The analyses
      indicated that adolescents from middle social status backgrounds and Asian
      families were more likely to stay in school than were those from lower social
      status backgrounds and Anglo Australian families; academic self-concept,
      achievement, perceptions of environments, and aspirations had a large independent
      association with staying in school; and there were significant differences in
      relationships among the aforementioned variables for adolescents from different
      ethnic groups and among those who decided to stay in or drop out of school.

PMID- 12230157
TI  - Monitoring of bacterial and parasitological contamination during various
      treatment of sludge.
AB  - Wastewater treatment results in the production of large quantities of sludge.
      Agricultural use is an interesting alternative provided that the health risks are
      taken into account. In France, a decree (1998) defines "sanitized" sludge as
      sludge that has been treated so that pathogens (Salmonella, enteroviruses, viable
      nematode eggs) are no longer detectable. The aim of this study was to determine
      the impact of various sludge treatments on 2 types of pathogens (Salmonella and
      nematode eggs). We also assessed the levels of micro-organisms that indicate
      faecal contamination (E. coli, Enterococci, sulfite-reducing anaerobes spores).
      Various treatment processes were analyzed: 4 biological, 3 chemical, 1 heat, 2
      storage and 4 sampling campaigns were carried out. Concerning the parasitological
      contamination of sludge at the entrance of all sites, concentrations of total
      nematode eggs and viable nematode eggs were highly heterogeneous (respectively,
      from 2 to 53 eggs/10 g DM and from 2 to 45 eggs/10 g DM) with viable eggs present
      in all samples. The total concentration of nematode eggs in the sludge was not
      greatly affected by treatment or storage, and was in the range < 1-66 eggs/10 g
      DM. However, the situation was different for mean viable egg counts. For four
      treatments, no viable eggs were detected. Mesophilic processes are inefficient at
      eliminating viable nematode eggs. Salmonella were systematically detected in all
      sludge samples at the entry to the station, except for limed sludge intended for
      storage. At the end of four treatments Salmonella had been totally eliminated.
      For the fecal contamination indicators, the largest decrease in E. coli
      contamination was observed following liming and after thermophilic treatment. The
      mesophilic treatments resulted in very small decreases in contamination. A
      similar pattern was observed with Enterococci. For the spores of sulfite-reducing
      anaerobe bacteria, with the exception of heat treatment, which reduced
      contamination by 3.2 log units, the maximum decrease in contamination was 1.7
      log. For storage of sludge, E. coli and Enterococci levels had decreased at first
      but then increased between 6 and 8 months of storage.

PMID- 12230158
TI  - Retention of inorganic oxyanions by organo-kaolinite.
AB  - A natural kaolinite (KGa-1b) was treated with the surfactant
      hexadecyltrimethylammonium bromide (HDTMA-Br) to a level twice that of the cation
      exchange capacity (CEC). Sorption of nitrate, arsenate, and chromate by the
      resultant organo-kaolinite was then quantified. Sorption of each oxyanion was
      well-described by the Langmuir isotherm. Sorption of nitrate was the greatest,
      with a Langmuir sorption maximum of 24 mmol/kg, although chromate showed the
      highest sorption affinity of 20 L/kg. Sorption of nitrate, arsenate, and chromate
      on organo-kaolinite was at least two orders of magnitude greater than their
      sorption on unmodified kaolinite. Desorption of the bromide counterion indicated
      that each of the oxyanions was retained by ion exchange on an HDTMA bilayer
      formed on the organo-kaolinite. Chromate sorption on the organo-kaolinite was
      unaffected by solution pH in the range 5-9, but decreased at pH 11 due to
      competition of OH- for anion exchange sites. Similarly, chromate exchange by
      organo-kaolinite was reduced in the presence of high background levels of
      chloride. Chromate was effectively retained when flowing through a packed bed of
      organo-kaolinite: after an input of more than 40 pore volumes, the effluent
      concentration of chromate was less than 10% of the input concentration, and 90%
      of the original HDTMA remained on the organo-kaolinite. The results demonstrate
      that properly prepared organoclays can remove oxyanions, as well as nonpolar
      organics, from contaminated waters.

PMID- 12230159
TI  - Filtration behaviors of Giardia and Cryptosporidium--ionic strength and pH
      effects.
AB  - The laboratory-scale filtration tests of Giardia cysts and Cryptosporidium
      oocysts in both 2 mm-phi glass beads and 2 mm-phi polystyrene beads filters were
      conducted to investigate their filtration behaviors. The protozoan parasites were
      used as target particles, while the chemical system altered by changing the
      electrolyte concentration and pH. The results significantly indicate that ionic
      strength have a positive effect on the removal efficiencies for Giardia cysts and
      Cryptosporidium oocysts. The removal efficiency of two filters for Giardia cysts
      slightly decreased from pH 2.4 to 8.7 and decreased significantly in pH as pH up
      to 8.7, while that for Cryptosporidium slightly rippled beyond pH 8.7, and with
      the decrease in pH up to pH 8.7. The experimental collision efficiencies from the
      interactions between colloids and the filter media were calculated with a semi
      empirical approach of the single sphere model and clean-bed filtration theory.
      The results also indicated that experimental collision efficiencies for (oo)cysts
      corresponded to the (oo)cysts removal efficiencies in all trials, and oocysts
      exhibits higher collision efficiencies than cysts.

PMID- 12230160
TI  - Natural inactivation of phosphorus by aluminum in atmospherically acidified water
      bodies.
AB  - Atmospheric acidification of catchment-lake ecosystems may provide natural
      conditions for the in-lake control of P cycling. This process is based on the
      elevated transport of aluminum from acidified soils and its subsequent
      precipitation in the water body and is described for strongly acidified forest
      lakes, acidified and circumneutral reservoirs, and a moderately acidified alpine
      lake. In water bodies with episodically or permanently acidified inflows a pH
      gradient develops between lake water and tributaries due to: (i) neutralization
      of acidic inflows after mixing with waters with undepleted carbonate buffering
      system, and/or (ii) the in-lake alkalinity generation dominated by biochemical
      removal of NO3- and SO4(2-). With the pH increasing towards neutrality, ionic Al
      species hydrolyze and form colloidal Al hydroxides (Al(part)) with large specific
      surfaces and strong ability to bind orthophosphate from the liquid phase.
      Moreover, Alpart settles and increases the P sorption capacity of the sediment.
      The presence of Al(part) on the bottom reduces orthophosphate release from
      sediments after its liberation from ferric oxyhydroxides during anoxia because
      Al(part) is not sensitive to redox changes. Consequently, the natural in-lake P
      inactivation may be expected in any water body with elevated Al input and a pH
      gradient between its inlet and outlet.

PMID- 12230161
TI  - Biodegradation of 1,4-dioxane in planted and unplanted soil: effect of
      bioaugmentation with Amycolata sp. CB1190.
AB  - 1,4-Dioxane is one of the most recalcitrant and toxic contaminants in the
      subsurface. This study investigated the potential to enhance dioxane
      biodegradation in both planted and unplanted soil, by adding the dioxane
      degrading actinomycete, Amycolata sp. CB1190. Dioxane was not removed within 120
      days in sterile controls or in viable microcosms not amended with CB 1190. Poplar
      root extract (40 mg/L as COD) stimulated dioxane degradation in bioaugmented
      soil, and 100 mg/L dioxane were removed within 45 days. Other co-substrates that
      enhanced dioxane degradation by CB1190 include tetrahydrofuran (THF) and 1
      butanol, while glucose and soil extract did not affect dioxane degradation. The
      stimulatory effect of THF was partly due to enhanced enzyme induction, while that
      of root extract and 1-butanol was attributed to additional growth of CB1190. In
      another experiment with dioxane added at 10 mg/kg-soil. reactors planted with
      hybrid poplar trees removed (by evapotranspiration and biodegradation in the root
      zone) more dioxane within 26 days than unplanted reactors, regardless of whether
      CB1190 was added. Nevertheless, CB1190 enhanced mineralization of [14C]-dioxane
      in all experiments. This enhancement was more pronounced in unplanted soil
      because plant uptake reduced the availability of dioxane for microbial
      degradation. These results suggest that bioaugmented phytoremediation is an
      attractive alternative to remove dioxane from shallow contaminated sites.

PMID- 12230162
TI  - An improved permeability model for fractal aggregates settling in creeping flow.
AB  - Aggregates often have mass fractal properties and there is, therefore,
      considerable interest in the hydrodynamics of mass fractal aggregates. There is
      no appropriate model in the literature to account for the non-homogeneous
      permeability within mass fractal aggregates. The new model proposed treats an
      individual aggregate as a self-similar object made up of a settling swarm of
      permeable spheres which are themselves made up of a settling swarm of sub-spheres
      and so on to the level of primary particles. This staged approach makes
      appropriate use of the fractal description of the aggregate to account for non
      homogeneous distribution of porosity and quantify the drag correction for flow
      through effects. It also allows the settling properties to be quantified for
      multiple level aggregate structures, such as those formed from microflocs or by
      restructuring.

PMID- 12230163
TI  - Wastewater treatment sludge as a raw material for the production of Bacillus
      thuringiensis based biopesticides.
AB  - Seven wastewater sludges of different origins and types were used as an alternate
      culture medium for producing Bacillus thuringiensis variety kurstaki HD-1. The
      sludge samples were used under three different preparations: without pre
      treatment, with acid treatment (hydrolysed sludge) and the supernatant obtained
      after centrifugation of the hydrolysed sludge. The sludge composition varied
      widely with origin and the type of sludge. Growth and sporulation were evaluated
      by the total viable cell count and spore count of the preparations. Growth,
      sporulation and endotoxin production were affected by the sludge origin.
      Hydrolysed sludge gave the highest viable cell and spore counts while the liquid
      phase (supernatant) gave the lowest. Non-hydrolysed primary sludge from
      Valcartier was unable to sustain bacterial growth because of its low pH.
      Bioassays were conducted against larvae of spruce budworm to evaluate entomotoxic
      potential of the preparations obtained. In general, sludge hydrolysis increased
      the entomotoxicity yields. Similar entomotoxicity was observed in Black Lake
      secondary sludge (4100 IU/microL) as that obtained in the reference soya medium
      (3800 IU/microL). The use of the sludge supernatant (liquid phase) was not
      recommended due to the low entomotoxic potential obtained.

PMID- 12230164
TI  - Comparative measurements of microbial activity in drinking water biofilters.
AB  - Tetrazolium reduction assays, phospholipid analysis, and 16S rRNA (rDNA) sequence
      analysis were applied to assess the distribution, composition and activity of
      microbial communities developing in biofilters treating non-ozonated and ozonated
      drinking water. The response of media-attached biomass to both operating
      temperature (3 degrees C vs. > 12 degrees C) and ozone application point was
      assessed. As judged by 2-(p-iodo-phenyl)-3-(p-nitrophenyl)-s-phenyl tetrazolium
      chloride (INT) reduction, the dehydrogenase activity in biofilter systems that
      were operated with non-ozonated water was 55% lower than in identical filters
      operating with ozonated water. There was no significant difference between the
      microbiological activity measured in a biofilter series treating ozonated water
      and an identical series where ozonated water was introduced at an intermediate
      point. The biomass levels in biofilter systems that were operated with ozonated
      water were 47% higher on average than identical systems operated with non
      ozonated water. Operating temperature had no significant impact on total biomass
      levels; however, specific dehydrogenase activity was 70% higher in systems
      operated at ambient temperatures (> 12 degrees C) than in systems held at 3
      degrees C. Phospholipid and rDNA analysis suggests that there was a community
      structure response to ozone application and operating temperature, but no
      response to different ozone application points.

PMID- 12230165
TI  - Analysis of bioassays with time-varying concentrations.
AB  - In the analysis of ecotoxicological bioassays the concentration of the test
      compounds is assumed to be constant. In many situations this assumption is
      questionable, as various processes may cause a substantial decline in the
      concentration during exposure. This leads to difficulties in the estimation of
      parameters that characterise the toxicity of the test compound. As a solution to
      this problem, time-varying concentrations are often replaced by their mean values
      for the estimation of toxicity parameters. However, Monte-Carlo simulations show
      that this approach results in biased estimates of the toxicity parameters. As an
      alternative approach, we propose models to estimate one important toxicity
      parameter, the no effect concentration, in situations where the concentration of
      the compound varies in time. These models are extensions of the DEBtox model
      (Kooijman and Bedaux, 1996) which is based on biological assumptions about
      toxicokinetics and toxic effects. We also propose a new approach for the
      estimation of toxicity parameters for strongly accumulating non-metabolisable
      compounds. This approach does not require any kinetics assumption. Computer
      simulation and experimental data confirm the relevance of the different
      proposals.

PMID- 12230166
TI  - Aerobic storage by activated sludge on real wastewater.
AB  - Activated sludge processes are often operated under dynamic conditions, where the
      microbial response can include, besides of growth, several COD removal
      mechanisms, and particularly the storage in form of polymers. While abundant
      evidence of aerobic storage under dynamic conditions with synthetic substrates
      can be found (Majone et al., Water Sci. Technol. 39(1) (1999) 61), there is still
      little knowledge about COD removal mechanisms with real activated sludge and
      wastewater. The aim of the present paper is therefore to give a direct evidence
      of storage phenomena occurring when a real sludge is mixed with influent
      wastewater and of their influence onto OUR profiles in typical respirometric
      batch tests. For this purpose, respirometric batch tests were performed on the
      same sludge by using acetate, filtered wastewater and raw wastewater as carbon
      source along with determination of acetate uptake and storage polymer formation.
      Comparison of results obtained has shown that poly-3-hydroxybutyrate (PHB)
      storage gives always the main contribution to acetate removal and that in the
      case of wastewater PHB is also formed from other substrates. PHB formation
      clearly occurs during the high-rate RBCOD-phase, however for wastewater it
      accounts for only a fraction (18-22%) of overall RBCOD removal, so calling for
      other unidentified storage compounds or other non-storage phenomena. In the low
      rate SBCOD phase of respirogram PHB is clearly utilised in tests with acetate as
      internal reserve material once the acetate is depleted. In tests with filtered
      and raw wastewater the PHB concentration decreases much slower, probably because
      more PHB is formed due to the availability of external SBCOD (soluble and not).
      Moreover, reported OUR in the SBCOD-phase from filtered or raw wastewater are
      quite higher than those reported in batch tests with acetate, so confirming a
      main contribution of external SBCOD. However, the respective contributions for
      utilisation of previously stored compounds and of external SBCOD cannot be easily
      separated by the comparison of tests on filtered and raw wastewater, because both
      substrates are simultaneously present also in tests with the filtered wastewater.
      As a side consequence, the chemical-physical method for evaluation of true
      soluble and biodegradable COD tends to overestimate the respirometry-based RBCOD,
      at least for the wastewater under observation. Even though modelling by ASM3
      (Gujer et al., Water Sci. Technol. 39(1) (1999) 183) makes it possible to well
      describe the whole experimental behaviour, it requires that much more storage
      compounds are formed than the experimentally observed PHB. These compounds have
      still to be identified and quantified in order to confirm the conceptual
      structure of ASM3.

PMID- 12230167
TI  - Degradation of medical x-ray film developing wastewaters by advanced oxidation
      processes.
AB  - Effluents from X-ray film developing processes feature high contaminant load (COD
      about 200 g/l). Identification of the main organics present in these wastewaters
      was performed by using liquid chromatography-mass spectrometry in electron impact
      mode, LC-(EI)MS. Both, unconsumed ingredients and sulphonated/hydroxylated
      derivatives and dimers yielded from the developing agents hydroquinone and
      phenidone were found to be the main organics contributing to the contaminant load
      of these effluents. Their potential degradation by oxidation with both photo- and
      thermal-Fenton reactions was investigated and the optimal degradation conditions
      were determined. Under these conditions the initial COD was reduced by about 97%
      within 6 h of treatment. The intermediates detected by LC-(EI)MS in the oxidation
      of hydroquinone and phenidone during the treatment were essentially hydroxylated
      derivatives and dimers and the residual organic matter was mainly made up of
      carboxylic acids. Reaction pathways for the oxidation of the developing agents
      hydroquinone and phenidone were proposed. The presence of many organic and
      inorganic components in the wastewaters did not affected the favoured oxidation
      route of these developers. The results obtained allow to assess the reduction of
      costs permitted in the treatment of X-ray effluents with the photo- and thermal
      Fenton reaction without affecting the degradation degree and quality of the
      discharge.

PMID- 12230168
TI  - Nitrogen transformations in a wetland receiving lagoon effluent: sequential model
      and implications for water reuse.
AB  - Constructed wetlands could be components of low-tech systems to treat and reuse
      wastewater in arid region. A key function of the wetland would be to provide
      additional N removal. To improve design criteria, a sequential model of nitrogen
      transformations (organic N --> ammonium: ammonium --> nitrate: nitrate -->
      nitrogen gas) was successfully calibrated and verified for a wetland in Kingman,
      Arizona. A sequential model has the ability to "recognize" species of nitrogen in
      the influent and predict species of nitrogen in the effluent. Model scenarios
      show that increasing nitrification rates in the summer and denitrification rates
      in the winter would improve nitrogen removal efficiencies. Several lines of
      evidence suggest that wintertime denitrification may be limited by carbon supply.
      Winter carbon supply could be augmented by routing a portion of the water through
      channels planted with dryland vegetation.

PMID- 12230169
TI  - Effect of addition of Rhodobacter sp. to activated-sludge reactors treating
      piggery wastewater.
AB  - Under aerobic conditions, the decay rates of purple nonsulfur bacteria
      (Rhodobacter sp.) in the light and dark follow first-order kinetics with rate
      constants of 0.22 and 0.32 day(-1), respectively. The performance of the
      conventional activated-sludge reactor (CASR) treating anaerobically pretreated
      piggery wastewater (656-1.110 mg chemical oxygen demand, COD/L) can be enhanced
      by the addition of Rhodobacter sp. By performing regressive and statistical
      analyses using the proposed model and experimental data, the kinetic constants k
      and Y(T), and the fraction of refractory organic materials (f) of the Rhodobacter
      sp.-supplemented activated-sludge reactor (RASR) are 40% larger, 21% less, and
      34% less than those of the CASR, respectively. From parametric sensitivity
      analyses, the substrate removal efficiencies of the CASR and RASR are most
      sensitive to the parameters k and the food to microorganisms ratio (F/M) but
      least sensitive to the parameter f; the specific oxygen utilization rates of the
      CASR and RASR are most sensitive to the parameters a and k but least sensitive to
      the parameter b.

PMID- 12230170
TI  - Film-pore diffusion model for the fixed-bed sorption of copper and cadmium ions
      onto bone char.
AB  - The sorption of copper and cadmium ions onto bone char in single component
      systems has been studied using fixed-bed column adsorbers. The effects of
      solution flowrate, initial metal ion concentration and bone char particle size
      have been studied. A film-pore diffusion model has been developed to predict the
      fixed-bed breakthrough curves for the two metal ions. A sensitivity analysis has
      been carried out to investigate the influence of the external mass transfer
      coefficient (film resistance), the effective diffusion coefficient (pore
      diffusion) and the solid phase loading capacity. It is found that under the
      experimental conditions employed in the study, film diffusional resistance was
      low and the Biot numbers were relatively high. Furthermore, a constant effective
      pore diffusivity was not sufficient to correlate the breakthrough curves
      accurately and a variable dependent effective diffusivity was required;
      suggesting a possible contribution from surface diffusion. Since the metal ion
      bone char systems take a long time to reach equilibrium, the solid phase loading
      capacity, as predicted by the "best-fit" equilibrium isotherm, was not suitable
      for use in the diffusional mass transport model and the mass balance solid phase
      loading was utilised instead.

PMID- 12230171
TI  - The EAWAG Bio-P module for activated sludge model No. 3.
AB  - An additional module for the prediction of enhanced biological phosphorus removal
      is presented on the basis of a calibrated version of ASM3. The module uses
      modified processes from ASM2d but neglects the fermentation of readily degradable
      substrate. Biomass decay is modeled in the form of endogenous respiration as in
      ASM3. Moreover, an additional glycogen pool and biologically induced P
      precipitation were not taken into account. The module was systematically
      calibrated with experimental data from various batch experiments, a full-scale
      WWTP and a pilot plant treating Swiss municipal waste water. A standard parameter
      set allowed all data to be simulated.

PMID- 12230172
TI  - Flocculation of kaolinite suspensions in water by chitosan.
AB  - Flocculation of kaolinite suspensions in water using chitosan was studied in the
      pH range 5-9 and the turbidity ranging from 10 to 160 NTU. Chitosan, in presence
      of trace quantities of a substance present in aqueous soil extracts, effectively
      reduces turbidity due to kaolinite by flocculation and settling. Flocculation
      efficiency is very sensitive to pH, and reaches a maximum at pH 7.5. The optimal
      chitosan concentration required to effect flocculation is independent of
      kaolinite concentration within the range examined. Flocculation is faster at
      higher concentrations of kaolinite and the flocs are large and settle rapidly.

PMID- 12230173
TI  - Percolation testing and hydraulic conductivity of soils for percolation areas.
AB  - The results of specific percolation tests are expressed in terms of field
      saturated hydraulic conductivity (Kfs) of the soil. The specific tests comprise
      the Irish SR 6 and the UK BS 6297 standard tests and the inversed auger hole and
      square hole tests employed for the design of land drainage. Percolation times
      from these tests are converted to Kfs values using unit gradient theory and the
      Elrick and Reynolds (Soil Sci. 142(5) (1986) 308) model which takes into account
      gravitational, pressure head and matric potential gradients. Kfs is then
      expressed as the inverse of the percolation rate times a constant, in this way
      the percolation rate can be directly related to Kfs of the soil. A plot of Kfs
      against percolation rate for the Irish SR 6 and the UK BS 6297 standard tests is
      asymptotic at Kfs values less than 0.2 m/d and greater than 0.8 m/d. This
      behaviour creates difficulty in setting limits for percolation rates in
      standards. Curves are provided which enable Kfs values to be read off from
      percolation tests without the restrictions of head range currently enforced, for
      example in the Irish SR 6 and BS 6297 standards. Experimental measurements of
      percolation rates and Kfs were carried out on two sands in the laboratory and in
      the field on two soils. Kfs of these four materials was also measured using a
      tension infiltrometer and the Guelph permeameter. The saturated hydraulic
      conductivities (Ks) of the sands were also estimated in a falling head laboratory
      apparatus and by the Hazen formula. There was good agreement between the
      different tests for Kfs on each material. Because percolation time continued to
      increase significantly in consecutive tests in the same test hole while Kfs
      became constant, the latter is a better measure of the suitability of soils for
      percolation.

PMID- 12230174
TI  - Polycyclic aromatic hydrocarbons in remote mountain lake waters.
AB  - Polycyclic aromatic hydrocarbons (PAH), including alkylated and sulfur
      derivatives, were identified and measured in the waters from three European
      remote mountain lakes during both ice-free and ice covered periods. The measured
      concentrations were in the same order in all three lakes (700-1100 pg/l). The PAH
      patterns in both dissolved and particulate water phases were dominated by the low
      molecular weight compounds (i.e. phenanthrene, fluoranthene and pyrene) in Lakes
      Redo (Pyrenees) and Gossenkolle (Alps). In contrast, the high molecular weight
      (HMW) compounds (i.e. chrysene+triphenylene, benzofluoranthenes, benzo[e]pyrene)
      were very significant in lake Ovre Neadalsvatn (Caledonian). These HMW PAH
      correspond to mixtures originating from high temperature combustion processes
      which have been photodegraded during long range atmospheric transport and
      parallel the PAH mixtures encountered in the underlying lake sediments. In
      contrast, dissolved PAH exhibit temperature dependence with higher concentrations
      found at water temperatures below 6-7 degrees C reflecting higher condensation
      from the atmospheric gas phase reservoir.

PMID- 12230175
TI  - Photosonochemical degradation of phenol in water.
AB  - The combination of ultrasound (US) and photochemistry has been used to degrade an
      aqueous solution of phenol. It was considerably more effective than ultrasound or
      ultraviolet (UV) light alone. Based on the results of total organic carbon (TOC)
      removal, it was shown that the synergistic action of ultrasound and ultraviolet
      light existed. Identification of the first intermediates of the reaction
      (hydroquinone, catechol, benzoquinone and resorcin) indicates that OH radicals
      are involved in the photosonochemical degradation mechanisms. The effects of
      parameters such as pH, saturating gases, and Fe2+ on the photosonochemical
      degradation have been studied. The experimental results have shown that lower pH
      and higher concentration of dissolved oxygen favor the phenol degradation and
      that the presence of Fe2+ enhanced TOC removal of phenol solutions.

PMID- 12230176
TI  - Risk assessment for Cryptosporidium: a hierarchical Bayesian analysis of human
      dose response data.
AB  - Three dose-response studies were conducted with healthy volunteers using
      different Cryptosporidium parvum isolates (IOWA, TAMU, and UCP). The study data
      were previously analyzed for median infectious dose (ID50) using a simple
      cumulative percent endpoint method (Reed and Muench, 1938). ID50s were derived
      using two definitions of infection: one as subjects having oocysts detected in
      stool by direct fluorescence assay, and the other by a clinical finding of
      diarrhea with or without detected oocysts (Chappell et al., 1998; Okhuysen et
      al., 1999). In the present study, the data were analyzed using the broader
      definition of infection (i.e., presence of oocysts in stool and/or diarrheal
      illness characteristic of cryptosporidiosis). Maximum likelihood dose-response
      parameter estimates for UCP, IOWA, and TAMU were 2980, 190, and 17.5,
      respectively. Based on these estimates, the ID50s of the three respective
      isolates were 2066, 132, and 12.1. The three oocyst isolates were considered
      representative of a larger population of human-infecting strains and analyzed as
      combined data using a hierarchical Bayesian model. Hyperparameters defined the
      distribution of dose-response parameters for the population of strains. Output
      from Markov Chain Monte Carlo analysis described posterior distributions for the
      hyperparameters and for the parameters of the IOWA, TAMU, and UCP strains. Point
      estimates of dose-response parameters produced by this analysis were similar to
      the maximum likelihood estimates. Finally, the utility of these results for
      probabilistic risk assessment was evaluated. The risk of infection from single
      oocyst doses was derived for a mixture of the three isolates (where IOWA, TAMU,
      or UCP are equally likely), and for an oocyst selected at random from the larger
      population of strains. These estimated risks of infection were 0.018 and 0.028,
      respectively.

PMID- 12230177
TI  - Use of solvents to enhance PAH biodegradation of coal tar-contaminated soils.
AB  - Bioremediation of coal tar-contaminated soils containing polycyclic aromatic
      hydrocarbons (PAHs) is highly challenging because of the low solubility and
      strong sorption properties of PAHs. Five coal tar-contaminated soils from former
      manufactured gas plant (MGP) sites were pretreated with two solvents, acetone and
      ethanol to enhance the bioavailability of the PAH compounds. The biodegradation
      of various PAHs in the pretreated soils was assessed using soil slurry reactors.
      The total PAH degradation rates for soils pretreated with solvents were estimated
      to be about two times faster than soils that were not pretreated with solvents.
      For example, the total PAH first order degradation rate constants were 0.165+/
      0.032, 0.147+/-0.020, and 0.076+/-0.009 day(-1) for Vandalia (EXC) soil that were
      pretreated with acetone, ethanol, and with no solvent, respectively. A
      distinctive advantage for soils pretreated with solvents was the enhanced removal
      of 5-ring PAH compounds such as benzo(a)pyrene and to a limited extent 4-ring
      compounds such as chrysene. Even for soils with 3.5% or more organic carbon
      content (two soils out of five), the degradation rate constants of chrysene were
      found to be two times faster than soils that were not pretreated. The degradation
      rate constants of benzo(a)pyrene were enhanced by 2-6 times for all five
      contaminated soils that were pretreated with solvents. To further elucidate
      trends that control the solvent treatment, the percent improvement in degradation
      rate constants (100 x rate constants for pretreated soils/rate constants for non
      treated soils) for 16 PAHs were found to correlate well with the PAH partition
      coefficients (K(oc)). Except for phenanthrene and the clay fraction of the soil,
      correlations between the percent improvement in degradation rates constants and
      several physical properties of the soils were poor and sporadic. This implies
      that the enhancement in PAH availability using solvent treatment was driven by
      the distribution of the PAHs between the solvent and the adsorbed PAHs.

PMID- 12230178
TI  - Effects of coagulation processes on aldehydes formation in groundwater treated
      with common oxidative agents.
AB  - This work is concerned with the effects of coagulation processes with two
      different coagulants (polyaluminum chloride (PACl) and Al2(SO4)3) on aldehydes
      formation during oxidation with common oxidants (ozone, chlorine and chlorine
      dioxide) in a particular groundwater source in Northern Banat region, Yugoslavia.
      Aldehydes concentrations in coagulated water were lower than in raw water. In
      contrast, obtained results showed that specific contents of these disinfection
      byproducts (microg mg(-1) TOC) showed an increase after coagulation processes in
      a number of samples. Results indicate that the choice of the coagulant-oxidant
      combination may be important as well as the type of filtration bed, retention
      time, and filter washing regime in the removal of aldehydes from water.

PMID- 12230179
TI  - A hybrid artificial neural network as a software sensor for optimal control of a
      wastewater treatment process.
AB  - For control and automation of biological treatment processes, lack of reliable on
      line sensors to measure water quality parameters is one of the most important
      problems to overcome. Many parameters cannot be measured directly with on-line
      sensors. The accuracy of existing hardware sensors is also not sufficient and
      maintenance problems such as electrode fouling often cause trouble. This paper
      deals with the development of software sensor techniques that estimate the target
      water quality parameter from other parameters using the correlation between water
      quality parameters. We focus our attention on the preprocessing of noisy data and
      the selection of the best model feasible to the situation. Problems of existing
      approaches are also discussed. We propose a hybrid neural network as a software
      sensor inferring wastewater quality parameter. Multivariate regression,
      artificial neural networks (ANN), and a hybrid technique that combines principal
      component analysis as a preprocessing stage are applied to data from industrial
      wastewater processes. The hybrid ANN technique shows an enhancement of prediction
      capability and reduces the overfitting problem of neural networks. The result
      shows that the hybrid ANN technique can be used to extract information from noisy
      data and to describe the nonlinearity of complex wastewater treatment processes.

PMID- 12230180
TI  - Biological nitrogen removal with enhanced phosphate uptake in a sequencing batch
      reactor using single sludge system.
AB  - Simultaneous biological phosphorus and nitrogen removal with enhanced anoxic
      phosphate uptake was investigated in an anaerobic-aerobic-anoxic-aerobic
      sequencing batch reactor ((AO)2 SBR). Significant amounts of phosphorus
      accumulation organisms (PAOs) capable of denitrification could be accumulated in
      a single sludge system coexisting with nitrifiers. The ratio of the anoxic
      phosphate uptake to the aerobic phosphate uptake capacity was increased from 11%
      to 64% by introducing an anoxic phase in an anaerobic aerobic SBR. The (AO)2 SBR
      system showed stable phosphorus and nitrogen removal performance. Average removal
      efficiencies of TOC, total nitrogen, and phosphorus were 92%, 88%, and 100%,
      respectively. It was found that nitrite (up to 10 mg NO2(-)-N/l) was not
      detrimental to the anoxic phosphate uptake and could serve as an electron
      acceptor like nitrate. In fact, the phosphate uptake rate was even faster in the
      presence of nitrite as an electron acceptor compared to the presence of nitrate.
      It was found that on-line sensor values of pH, ORP, and DO were somehow related
      with the dynamic behaviours of nutrient concentrations (NH4+, NO3-, and PO4(3-))
      in the SBR. These on-line sensor values were used as real-time control parameters
      to adjust the duration of each operational phase in the (AO)2 SBR. The real-time
      controlled SBR exhibited better performance in the removal of phosphorus and
      nitrogen than the SBR with fixed-time operation.

PMID- 12230181
TI  - Chlorophyll-a determination via continuous measurement of plankton fluorescence:
      methodology development.
AB  - A methodology is presented for the continuous measurement of chlorophyll-a
      concentration due to plankton, in surface water environments. A Turner 10-AU
      fluorometer equipped with the F4T5.B2/BP lamp (blue lamp), a Cs 5-60 equivalent
      excitation path filter, and a 680 nm emission filter, has been used. This
      configuration allows the in vivo, in situ determination of chlorophyll-a by
      measuring the fluorescence due to the pigments. In field work the fluorometer,
      data logging and positioning equipment were placed aboard a manageable boat which
      navigated following a scheme of regularly spaced crossings. Some water samples
      were collected during the measurement for laboratory chlorophyll-a measurements
      by the spectrophotometric method, thus providing for calibration and comparison.
      Spatial chlorophyll-a concentration distributions can be easily defined in large
      volumes, such as reservoirs, etc. Two distinct environments have been monitored:
      in the Vargem das Flores reservoir chlorophyll-a concentrations varied between
      0.7 and 2.6 mg/m3, whereas in the Lagoa Santa lake these values lied in the 12 to
      18 mg/m3 range. The simplicity, versatility and economy of the method, added to
      the large amount of data that can be gathered in a single run, clearly justify
      its use in field environmental studies.

PMID- 12230182
TI  - Removal of Pb(ii) from aqueous/acidic solutions by using bentonite as an
      adsorbent.
AB  - The ability of bentonite clay to remove Pb(II) from aqueous solutions and from
      nitric acid, hydrochloric acid and perchloric acid solutions (1.0-1 x 10(-5)) has
      been studied at different optimized conditions of concentrations, amount of
      adsorbent, temperature, concentration of electrolyte and pH. Maximum adsorption
      of Pb(II), i.e. > 98% has been achieved in aqueous solutions, while 86% is
      achieved from 1.0 x 10(-5) M HCl using 0.5 g of bentonite. The adsorption
      decreases by increasing the concentration of electrolytes. Flame atomic
      absorption spectrometer was used for measuring lead concentration. Isotherm
      analysis of adsorption data obtained at 25 degrees C, 30 degrees C, 40 degrees C
      and 50 degrees C showed that the adsorption pattern of lead on bentonite followed
      the langmuir isotherm and freundlich isotherm, respectively. DeltaH(o) and
      deltaS(o) were calculated from the slope and intercept of ln K(D) vs. I/T plots.

PMID- 12230183
TI  - Removal of organic pollutants from industrial wastewater by electrogenerated
      Fenton's reagent.
AB  - This study was performed to investigate the treatment of an industrial wastewater
      mainly containing naphthalene- and anthraquinone-sulphonic acids, by
      electrogenerated Fenton's reagent. The hydrogen peroxide was produced in situ by
      electrochemical reduction of oxygen on graphite-felt cathodes and the Fe2+ ions
      were also regenerated by cathodic reduction of Fe3+. The influence of cathode
      potential, Fe2+ concentration and electrode surface pre-treatment on chemical
      oxygen demand (COD) removal and colour fading were studied. Results indicated
      that the higher COD removal was obtained in the presence of 3 mM of ferrous ions
      working at a constant potential of -1 V vs. SCE. Moreover, it was shown that both
      chemical and electrochemical pre-treatments of the cathode surface resulted in a
      decrease of COD depletion.

PMID- 12230184
TI  - Particle size distribution in effluent of trickling filters and in humus tanks.
AB  - Particles and aggregates from trickling filters must be eliminated from
      wastewater. Usually this happens through sedimentation in humus tanks.
      Investigations to characterize these solids by way of particle size measurements,
      image analysis and particle charge measurements (zeta potential) are made within
      the scope of Research Center for Science and Technology "Fundamentals of Aerobic
      biological wastewater treatment" (SFB 411). The particle size measuring results
      given within this report were obtained at the Ingolstadt wastewater treatment
      plant, Germany, which served as an example. They have been confirmed by similar
      results from other facilities. Particles flushed out from trickling filters will
      be partially destroyed on their way to the humus tank. A large amount of small
      particles is to be found there. On average 90% of the particles are smaller than
      30 microm. Particle size plays a decisive role in the sedimentation behaviour of
      solids. Small particles need sedimentation times that cannot be provided in
      settling tanks. As a result they cause turbidity in the final effluent. Therefore
      quality of sewage discharge suffers, and there are hardly advantages of the fixed
      film reactor treatment compared to the activated sludge process regarding
      sedimentation behaviour.

PMID- 12230185
TI  - Membrane filtration of two sulphonamides in tertiary effluents and subsequent
      adsorption on activated carbon.
AB  - The adsorption behaviour of two polar organic micropollutants (N-n
      butylbenzenesulphonamide and sulphmethoxazole) onto powdered activated carbon
      (PAC) under competitive conditions prior to and after filtration with a tight
      ultrafiltration membrane was examined. The sulphonamides were spiked into
      microfiltered tertiary municipal effluent in microg L(-1) quantities.
      Ultrafiltration of these effluents resulted in better adsorbability for both the
      micropollutants and the background organic matter in the permeates compared to
      the feed waters. This behaviour seems to be caused by a reduced blocking of
      micropores by lower concentrations of high molecular weight compounds in membrane
      filtrates. A combined treatment of ultrafiltration prior to adsorption can
      therefore reduce the carbon demand for potentially harmful micropollutants in
      effluents.

PMID- 12230186
TI  - Errors in bound water measurements using centrifugal settling method.
AB  - Centrifugal settling method (CSM) is commonly used to estimate the bound water
      content in sludges. The sludge sediment matrix should be purely plastic for
      accurate measurements to the bound water content. This communication, however,
      addressed for the first time that, owing to the inhibited elasticity of the
      sludge matrix, sediment height rebound was commonly observed for the flocculated
      sludge. Also, different sludges could have distinct elastic responses after
      centrifugation. There existed no simple correlation to incorporate the elastic
      rebound of sludge sediment in bound water measurement. The possible errors
      incorporated into CSM for measuring bound water contents were highlighted.

PMID- 12230187
TI  - Oocysts of Cryptosporidium parvum and model sand surfaces in aqueous solutions:
      an atomic force microscope (AFM) study.
AB  - Oocysts of C. parvum have been associated with several waterborne outbreaks of
      gastro-enteric disease. Currently, one of the main barriers to oocyst
      contamination of drinking waters is provided by sand-bed filtration. In this
      study an atomic force microscope (AFM) has been used to measure the force of
      interaction between oocysts of C. parvum and a model sand surface (silicate
      glass). The AFM force curves have been compared and contrasted with the
      corresponding electrical potentials obtained from electrophoretic measurements
      (zeta). It has been found that the surface of C. parvum oocysts possesses a hairy
      layer, most likely a result of surface proteins extending into solution. The
      hairy layer imposes a steric repulsion between the oocyst and sand surface, in
      addition to any electrostatic repulsion. The hairy layer collapsed to varying
      extents in the presence of dissolved calcium and dissolved organic carbon,
      indicating that the oocysts may be more readily adsorbed onto the model sand
      surface under these conditions. Conversely, as the two surfaces are pulled apart,
      the occasional attachment of oocyst surface proteins to the model sand surface
      can result in adhesion. The AFM results offer new insights into the oocyst
      surface of C. parvum, and the mechanism of interaction with model sand surfaces
      under conditions relevant to sand-bed filtration.

PMID- 12230188
TI  - Elimination of free-living amoebae in fresh water with pulsed electric fields.
AB  - This study investigates the effects of pulsed electric fields on the inactivation
      of trophozoite form of Naegleria lovaniensis Ar9M-1 in batch and flow processes,
      systematically examining the lethal effect of field strength, pulse duration,
      number of pulses, and pulse frequency. Our results show that amoebae eradication
      is modulated by pulse parameters, composition of the pulsing medium, and
      physiological state of the cells. Cell survival is not related to the energy
      delivered to the cell suspension during the electrical treatment. For a given
      energy a strong field applied for a short cumulative pulse duration affects
      viability more than a weak field with a long cumulative pulsation. We also
      determine the optimal electrical conditions to obtain an inactivation rate higher
      than 95% while using the least energy. Flow processes allow to treat large-scale
      volumes. Our results show that the most efficient flow process for amoeba
      eradication requires a field parallel to the flow. Pulsed electric fields are a
      new and attractive method for inactivating amoebae in large volumes of fresh
      water.

PMID- 12230189
TI  - The effect of irrigation on tile sediment transport in a headwater stream.
AB  - A field-scale no-till corn plot (120 m x 90 m) located on a tile drained silt
      loam soil near Kintore, Ontario was irrigated with 2.5 cm of water over a 3 h
      period to examine the effects of irrigation on tile sediment transport in a
      headwater stream. Flow characteristics and the composition, concentration and
      size distribution of suspended solids were measured at the tile outlet, an
      upstream reference site and three sites located downstream of the tile drain.
      Results show that tile sediments at the study site are fine-grained (D50
      approximately 5.0 microm) and consist primarily of quartz, anorthite/albite,
      dolomite and calcite. Sediment concentrations in tile effluent increased from 8
      to 57 mg L(-1) after 1.5 h of irrigation and reached a maximum of 72 mg L(-1).
      The sediment yield from the tile drain for the irrigation event was 4.6 kg ha(
      1). An unsteady, mobile boundary flow model (MOBED) was used to predict flow
      characteristics in the stream. According to the MOBED model, bed shear stress in
      the stream was approximately 6 N m(-2). This value is significantly greater than
      the critical shear stress for complete suspension of 1 N m(-2) for tile sediments
      as determined from laboratory experiments using a rotating circular flume. Grain
      size distributions of suspended solids in the stream were close to the dispersed
      size distribution because of the high shear stress in the receiving stream.

PMID- 12230190
TI  - PCB sources, transformations, and contributions in recent Fox River, Wisconsin
      sediments determined from receptor modeling.
AB  - The PCB contamination in lower Fox River sediments was investigated in order to
      identify possible PCB sources, contributions, and transformations, using two
      receptor models. Congener specific sediment PCB data from sites immediately
      upstream of DePere dam to Green Bay that had been gathered for the Green Bay/Fox
      River Mass Balance Study, were used in this analysis. The first receptor model is
      a self training factor analysis (FA) model with non-negative constraints that was
      applied to identify the PCB sources and significant congener patterns. The second
      is a chemical mass balance model (CMB) in which published Aroclor sources,
      inferred from our FA model, were used to apportion these Aroclors to each sample.
      The FA model indicated two significant factors, the major one being Aroclor 1242
      and the other, a profile dominated by low chlorinated congeners, indicating a
      possible PCB alteration profile. This profile had significant contributions to
      samples at or around sites with total PCB concentrations higher than 50 ppm,
      indicating a potential anaerobic dechlorination activity. It was also deduced
      from the FA model that very small contributions of more highly chlorinated
      Aroclors may be present in the system. The results from the CMB model confirmed
      that the system is dominated by Aroclor 1242. Its average contribution was 95%,
      with small amounts of Aroclor 1254 (2%) and 1260 (1%). Two of the samples,
      located in the vicinity of point sources, showed high contributions of Aroclor
      1016 by the CMB model. This is interpreted as an altered Aroclor profile
      resembling the less chlorinated Aroclor 1016. Contributions obtained form the CMB
      and FA models show similar patterns.

PMID- 12230191
TI  - Solubilization of polycyclic aromatic hydrocarbon mixtures in micellar nonionic
      surfactant solutions.
AB  - This study sought to examine the solubilization of mixtures of the polycyclic
      aromatic hydrocarbons (PAHs) in solutions of the nonionic surfactants: Tween 20,
      Tween 80, Triton X 100, Brij 35, and Brij 58. When pyrene (PYR), fluoranthene
      (FLA), and phenanthrene (PHE) were solubilized from two-PAH mixtures, the PAH
      concentrations and molar solubilization ratios deviated very little from those as
      found in the single-PAH systems. When these PAHs were solubilized from the three
      PAH mixtures, however, not all three PAHs reached their single-PAH solubilities.
      When the PAHs were added sequentially to surfactant solution, the PAH added last
      reached its single-PAH solubility, while the concentration of other two PAHs were
      lowered by 14-45%. When the PAHs were added simultaneously to the surfactant
      solution, the composition of the solid phase influenced which PAH reached its
      single-PAH solubility. For solids containing equal mole fractions of all three
      PAHs, FLA and PHE dissolved in surfactant solution to a lesser extent than the
      single-PAH systems. In similar systems containing no surfactant, only FLA
      solubility decreased. As the mole fraction of a PAH in the solid phase increased,
      its solubility in the micelle phase (and in the aqueous phase) increased up to
      the solubility limit. Based on these studies, both PAH-PAH interactions and
      micelle-PAH interactions should be taken into account when predicting the
      concentrations of PAH mixtures in micellar surfactant solutions. This should be
      done because PAH-PAH interactions can influence aqueous solubility, while micelle
      PAH interactions can affect the distribution of PAHs in the micellar phase, which
      may change as the mixture composition changes.

PMID- 12230192
TI  - Polyhydroxyalkanoates form potentially a key aspect of aerobic phosphorus uptake
      in enhanced biological phosphorus removal.
AB  - Eighteen anaerobic/aerobic batch experiments were conducted with a variety of
      volatile fatty acids (VFAs) on a sequencing batch reactor (SBR) population
      displaying enhanced biological phosphorus removal (EBPR). A statistically
      significant (P << 0.01 for all variables) correlation between aerobic phosphorus
      uptake and polyhydroxyalkanoates (PHAs) quantity and form was observed. The
      results suggest that poly-3-hydroxy-butyrate (3HB) results in significantly
      higher aerobic phosphorus (P) uptake per unit mmoles as carbon (mmoles-C) than
      poly-3-hydroxy-valerate (3HV). The results showed that acetic and isovaleric
      acids resulted in higher P removals (relative to propionic and valeric acids)
      during EBPR batch experiments not because of higher PHAs quantity, but largely
      because the predominant type was 3HB rather than 3HV. In contrast propionic and
      valeric acids resulted in 3HV, and showed much lower aerobic P uptake per unit
      PHAs.

PMID- 12230193
TI  - The decay of chlorine associated with the pipe wall in water distribution
      systems.
AB  - Free chlorine decay rates in water distribution systems for bulk and wall demands
      should be modelled separately as they have different functional dependencies. Few
      good quality determinations of in situ wall demand have been made due to the
      difficulty of monitoring live systems and due to their complexity. Wall demands
      have been calculated from field measurements at 11 locations in a distribution
      system fed from a single source. A methodology for the laboratory determination
      has been evolved and shown to give results that are similar to the in situ
      results. Pipe materials were classified as either having high reactivity (unlined
      iron mains) or low reactivity (PVC, MDPE and cement-lined ductile iron). The
      results indicate that wall decay rates for the former are limited by chlorine
      transport and for the latter by pipe material characteristics. The wall decay
      rate is inversely related to initial chlorine concentration for low reactivity
      pipes. In general, water velocity increases wall decay rates though the
      statistical confidence is low for low reactivity pipes. A moderate biofilm
      coating did not influence the wall decay rate for low reactivity pipes.

PMID- 12230194
TI  - Treatment of domestic wastewater using the nutrient film technique (NFT) to
      produce horticultural roses.
AB  - Removal of organic matter, nitrogen and phosphorus was investigated in a pilot
      based on the nutrient film technique system used for horticultural production.
      Rosebushes producing commercial roses were set on an inclined impermeable surface
      over which a thin film of domestic wastewater flowed directly through the root
      matrix. The roses produced with wastewater as nutrient solution were
      qualitatively and quantitatively similar to those produced traditionally and can
      be marketable. In the presence of the rosebushes, the lowering of chemical oxygen
      demand (COD), biological oxygen demand (BOD5) and suspended solids (SS) increased
      with their influent strengths in a linear fashion correlation. Whatever the
      pollutant load of the influent, within the range studied, the level of organic
      pollution required to allow the discharge of the effluent into water courses was
      reached after 24 h of treatment. At this time, the COD reached 39 +/- 13 mg L(
      1), the BOD5 7 +/- 4 mg L(-1) and the SS 8 +/- 6 mg L(-1). The removal
      percentages were 89, 95 and 94, respectively, whereas without plants they were
      55, 33 and 53, respectively. The rosebushes had a beneficial effect on the
      removal of phosphorus from 20% to 23% greater in their presence than without. In
      presence of plants, the nitrate was the principal form of nitrogen from 48 h of
      treatment whereas without rosebushes, nitrite represent more than 20% of initial
      nitrogen whatever the treatment duration. The root matrix served not only as a
      filter for the organic matter, but also provided a microhabitat suitable for
      nitrifying bacteria and heterotrophic micro-organisms, which responded rapidly to
      the pollutant load.

PMID- 12230195
TI  - A novel in situ technology for the treatment of nitrate contaminated groundwater.
AB  - A novel in situ membrane technology was developed to remove nitrate (NO3-) from
      groundwater. Membrane-fed hydrogen gas (H2) was used as an electron donor to
      stimulate denitrification. A flow-through reactor fit with six hollow-fiber
      membranes (surface area = 93 cm2) was designed to simulate groundwater flowing
      through an aquifer with a velocity of 0.3 m/day. This membrane technology
      supported excellent NO3- and nitrite (NO2-) removal once H2 and carbon
      limitations were corrected. The membrane module achieved a maximum H2 flux of
      1.79 x 10(-2) mg H2/m2 s, which was sufficient to completely remove 16.4 mg/L
      NO3(-)-N from a synthetic groundwater with no NO2- accumulation. In addition,
      this model in situ treatment process produced a high quality water containing
      <0.5 mg/L total organic carbon.

PMID- 12230196
TI  - Intermittent filtration of wastewater--removal of fecal coliforms and fecal
      streptococci.
AB  - Removal of fecal coliforms and fecal streptococci was monitored over a period of
      13 months in 14 buried pilot scale filters, treating septic tank effluent. The
      effects of grain size, hydraulic dosing rate and distribution method were
      investigated. Two different natural sands (sorted sand and unsorted sand) and
      three different types of light weight aggregates (LWA 0-4 mm, LWA 2-4 mm and
      crushed LWA 0-3 mm) were used. Intermittent dosing rates from 20 to 80 mm/day in
      12 doses per day were applied to the filters by uniform pressure distribution or
      point application by gravity dosing. Removal of fecal coliforms was more than
      three orders of magnitude higher in the media with the finest grain sizes
      (unsorted sand) as compared to the coarsest media (LWA 0-4 mm and LWA 2-4 mm)
      operated under same conditions. Fecal streptococci were determined only in
      effluent from filters with LWA 0-4 mm and LWA 2-4 mm. Higher removal of fecal
      coliforms was observed in pressure dosed filters compared to gravity dosed
      filters. A lower removal was observed by increasing the hydraulic dosing rate.
      Minimum retention time was found to be a key parameter for predicting removal of
      bacteria in unsaturated, aerobic filters. At minimum retention times lower than
      about 50 h, there was a correlation of 0.96 between retention time and removal of
      fecal coliforms. Retention times longer than 50 h gave almost complete removal of
      fecal coliforms.

PMID- 12230197
TI  - Electrochemical generation of the Fenton's reagent: application to atrazine
      degradation.
AB  - The degradation of refractory chemicals in water requires chemical oxidation by
      hydroxyl radicals. Among the systems that may be used to generate OH(o), the
      Fenton's reagent consists of the mixing of ferrous iron and hydrogen peroxide.
      Even though this system is very simple, the oxidation of an organic compound is
      difficult to control and the ferrous iron regeneration is limited. Very recently,
      electrochemical systems have merged that allow the electrochemical production of
      ferrous iron and/or hydrogen peroxide, thereby allowing the generation of OH(o).
      So a simple electro-Fenton system has been used and tested for its efficiency in
      producing hydroxyl radicals. Atrazine was chosen as a model organic compound as
      its reaction with OH(o) has been extensively studied. Comparison with the
      classical Fenton system gives advantage to the electrochemical system, due to a
      more thorough oxidation of atrazine.

PMID- 12230198
TI  - Effect of NOM and biofilm on the removal of Cryptosporidium parvum oocysts in
      rapid filters.
AB  - Laboratory experiments were performed to evaluate the effects of biofilm and
      natural organic matter (NOM) on removal of Cryptosporidium parvum oocysts from
      water by filtration. The bench-scale rapid filters consisted of 2.54 cm ID x 30.5
      cm polycarbonate plastic columns packed with 0.55 mm spherical glass beads to a
      depth of 25 cm and a porosity of 40%. Calcium chloride (0.01 M) served as the
      coagulant in most of the experiments. The oocyst removal efficiency decreased
      from 51 +/- 6% for a clean bed to 23 +/- 3% for the biofilm-coated bed and to 14
      +/- 1% in the presence of 5 ppm of NOM. The oocyst removal for an experiment with
      a combination of biofilm-coated filter media and NOM was similar to that for the
      experiment with NOM alone (15 +/- 1%). The zeta potential values for the oocysts
      pre-equilibrated with NOM were significantly more negative than those obtained
      for untreated oocysts. This suggests that NOM enhanced the electrostatic
      repulsion between the oocysts and the negatively charged glass beads.
      Fortunately, use of alum as coagulant at a dosage sufficient to neutralize the
      surface charge of the NOM-coated oocysts resulted in a high removal efficiency
      (73 +/- 6%). Pre-equilibration of the oocysts with NOM also increased the
      hydrophobicity of the oocysts, but this was deemed to have a negligible effect on
      deposition onto the glass beads. The results of these experiments suggest that
      water treatment facilities treating source waters with moderate organic matter
      concentrations and/or employing biologically active filters have a greater
      potential for oocyst breakthrough and proper coagulation is critical for
      effective removal of oocysts in the filters.

PMID- 12230199
TI  - Passive dissolution of hydrogen gas into groundwater using hollow-fiber
      membranes.
AB  - A new hollow-fiber membrane remediation system has recently been developed to
      passively supply groundwater with dissolved hydrogen (H2) to stimulate the
      biodegradation of chlorinated solvents. Understanding the mass transfer behavior
      of membranes under conditions of creeping flow is critical for the design of such
      systems. Therefore, the objectives of this research were to evaluate the gas
      transfer behavior of hollow-fiber membranes under conditions typical of
      groundwater flow and to assess the effect of membrane configuration on gas
      transfer performance. Membrane gas transfer was evaluated using laboratory-scale
      glass columns operated at low flow velocities (8.6-12,973 cm/d). H2 was supplied
      to the inside of the membrane fibers while water flowed on the outside and normal
      to the fibers (i.e. cross-flow). Membrane configuration (single fiber and fabric)
      and membrane spacing for the fabric modules did not affect gas transfer
      performance. Therefore, the results from all of the experiments were combined to
      obtain the following dimensionless Sherwood number (Sh) correlation expressed as
      a function of Reynolds number (Re) and Schmidt number (Sc): Sh =
      0.824Re(0.39)Sc(0.33) (0.0004<Re<0.6). This correlation is useful for predicting
      the rate of transfer of any gas from clean membranes to flowing water at low Re.
      This correlation provides a basis for estimating the membrane surface area
      requirements for groundwater remediation as illustrated by a simple example.

PMID- 12230200
TI  - Aqueous solubilities of non-ortho and mono-ortho PCBs at four temperatures.
AB  - The temperature-dependent aqueous solubilities of 12 non-ortho and mono-ortho
      coplanar PCBs (IUPAC Nos. 77, 81, 105, 114, 118, 123, 126, 156, 157, 167, 169,
      and 189) were determined at 5 degrees C, 15 degrees C, 25 degrees C, and 35
      degrees C. A generator-column/extractor-column technique was used, followed by
      off-line GC/ECD analysis. The relative standard deviations for the measurements
      were < or = 7.4%. The determined solubilities increase exponentially with
      temperature from 5 degrees C to 35 degrees C for all 12 tested PCBs, and their
      enthalpies of solution were determined to range from 22.3 to 45.0 kJ/mol. The
      determined solubilities of PCB 77 at 25 degrees C were further compared with the
      results reported previously and with the calculated data. Within homolog groups,
      congeners with more ortho-substitution generally have greater aqueous
      solubilities. The measured aqueous solubilities of 58 congeners compiled from the
      literature and from this study were used for evaluation of quantitative structure
      property relationships relating chlorine substitution pattern to the aqueous
      solubilities. A useful equation by which to estimate aqueous solubilities was
      derived on the basis of multi-regression analysis, which employs easily
      calculable molecular descriptors. The validity of this equation is demonstrated
      by comparison of the estimated values with experimental values. This newly
      developed model agrees well with log K(ow)-based model predictions.

PMID- 12230201
TI  - Accelerated mineralization of the drug Diclofenac via Fenton reactions in a
      concentric photo-reactor.
AB  - The complete mineralization of concentrated solutions of Diclofenac (2-[(2,6
      dichlorophenyl) amino] benzene-acetic acid) sodium salt C14H10C12NO2Na was
      carried out in a concentric cylindrical immersion photoreactor in batch mode
      operation. Irradiation with a lamp emitting light at 254 nm (400 W) achieved
      total mineralization of Diclofenac solutions (0.062 mM or TOC 20 mg C l(-1)) in
      times under an hour. The mineralization was carried out via Fenton photo-assisted
      treatment. A determination of the solution parameters was carried out to optimize
      the time of the Diclofenac pretreatment, the type and intensity of the light
      source, the effect of the concentrations of Fe-ions and the oxidant added in
      solution and the reactor recirculation rate. Diclofenac disappearance was
      monitored by high liquid pressure chromatography (HPLC). Concomitantly, the
      aromatic and aliphatic intermediates were also monitored under low-energy (36 W)
      light irradiation at 366 nm in order to be able to detect the intermediates by
      HPLC in the minute time scale. The decrease of the chemical oxygen demand was
      followed during Diclofenac degradation. The activation energy for the
      mineralization of Diclofenac was determined to be 4.02 Kcal mol(-1).

PMID- 12230202
TI  - Optimisation of the coagulation-flocculation process of raw water by optimal
      design method.
AB  - In the present paper, a systematic study of the influence of raw water quality
      and operating conditions on the effectiveness of the coagulation-flocculation
      process using aluminium sulphate (AS) is presented. The influence of raw water
      composition is studied at two levels, fractional factorial designs and a Doehlert
      uniform shell design to determine the influence of the operating conditions. The
      analysis of the experimental responses (residual turbidity and minimally AS dose
      are denoted as (Tu(m)) and (AS(m)), respectively) shows that the parameters which
      have the greatest influence change depending on the response. It is not always
      possible, for a given water composition, to obtain simultaneously low residual
      turbidity and minimally AS dose. However, under the conditions of this study, the
      search for a criterion of optimisation must bear the minimisation of residual
      turbidity, because it remains the principal criterion of effectiveness of the
      process, even, if in a few cases, it results in an increase in the cost of
      treatment.

PMID- 12230203
TI  - Evaluation of aluminum-silicate polymer composite as a coagulant for water
      treatment.
AB  - Aluminum-silicate polymer composite (PASiC), a new kind of inorganic coagulant,
      was produced by two approaches: (1) hydroxylation of the mixture of AlCl3 and
      fresh polysilicate (PASiCc); (2) hydroxylated polyaluminum-chloride (PAC)
      combined with fresh polysilicate (PASiCm). The PASiC products had the following
      properties: Al2O3 content = 6.40-7.30%, SiO2 content = 0.40-0.82%, Al/Si ratios =
      10-20, basicity (OH/Al molar ratio, denoted B) = 1.2-2.0. The coagulation
      behaviour of PASiC and PAC under conditions typical for coagulation and
      flocculation in water treatment were investigated by studying the rate of floc
      size development, the variety of streaming current value, the efficiency of
      turbidity removal and the effect of pH on the turbidity removal efficiency, and
      the stability of PASiC. The results detailed in this study suggest that, compared
      with PAC, PASiC may enhance aggregating efficiency and give better coagulating
      effects, but weaken charge effectiveness in coagulation process or become
      unstable when stored for longer time, especially at higher B value and lower
      Al/Si ratio. The coagulating effect of PASiC is closely linked to the preparation
      procedure. With the increase of B value and the decrease of Al/Si ratio, the
      coagulation efficiency of PASiC increases, and at the same B value and Al/Si
      ratio, PASiCc seems to give a little better coagulation effect than PASiCm but
      less stability. The Al/Si ratio should not be too low or the B value should not
      be too high, otherwise, the PASiC products tend to become cloudy or partly
      gelatinous, which will make them loss some coagulation efficiency.

PMID- 12230204
TI  - H2O2/TiO2 photocatalytic oxidation of metol. Identification of intermediates and
      reaction pathways.
AB  - The applicability of H2O2 to increase the efficiency of TiO2 photocatalytic
      degradations was investigated. The photographic developer metol [N-methyl-p
      aminophenol] that does not adsorb on the surface of TiO2 particulates was used as
      a model for this purpose. It was proved that metol was mineralised under
      oxidation with H2O2/TiO2/UV through different thermal and photochemical
      reactions. Identification of intermediates by both HPLC-electron impact-MS and
      HPLC-electrospray ionisation-MS helped to elucidate the role of H2O2 and TiO2 in
      the degradation process and to establish degradation pathways. Intermediates
      yielded were partially oxygenated aromatic species and dimers, which were
      amenable to oxidation. The optimal degradation conditions found for
      mineralisation were 0.4 M H2O2, 5 mg/ml TiO2, pH 9 and irradiation centred at 360
      nm (4.9 mW/cm2). The use of oxidants opens an interesting medium to the treatment
      of effluents containing a diversity of organics since they increase substantially
      the efficiency of TiO2 photocatalytic degradations.

PMID- 12230205
TI  - Nutrient and grazing factors in relation to phytoplankton level in a eutrophic
      shallow lake: the effect of low macrophyte abundance.
AB  - The ability of submerged macrophytes to moderate the structure of food webs with
      respect to lake eutrophication management has been intensively studied in recent
      years. Many lake managers have adopted the option of increasing macrophyte
      abundance in order to restore eutrophic waters, with a view to improve water
      quality, increase water transparency and reduce phytoplankton biomass. These
      studies are mostly based upon the comparison of macrophyte-rich and macrophyte
      free waters. There is less quantitative information on how different levels of
      macrophyte abundance, in particular very low levels, influence ecosystem
      structure, or vice versa, within the same ecosystem. This paper takes a
      multivariate statistical approach to examine ecosystem function with low
      macrophyte abundance (ca. 5%) in the context of nutrient-phytoplankton
      zooplankton interaction in a eutrophic shallow lake. It shows that with low
      levels of macrophyte coverage, phytoplankton biomass was only limited by nutrient
      (TP and Si) availability, whilst nutrient (Si) as well as grazing (zooplankton
      and Daphnia) factors were both limiting phytoplankton levels in macrophyte-free
      waters. With respect to interactions between Daphnia and chlorophyll-a, the
      results suggest that low macrophyte cover does not result in a reduction of
      phytoplankton biomass due to the presence of Daphnia. Rather, low macrophyte
      cover provides a refuge that maintains constant Daphnia predation, so reducing
      chlorophyll-a fluctuation. These results add credence to the causal
      interpretation of different interactions amongst nutrients, phytoplankton and
      zooplankton at very low macrophyte densities.

PMID- 12230206
TI  - Are trophic and diversity indices based on macrophyte communities pertinent tools
      to monitor water quality?
AB  - Diversity and trophic indices based on macrophyte communities were calculated to
      test their pertinence to monitoring water quality in the Northern Vosges (NE of
      France). Highly significant correlations were found between the four tested
      chemical variables (bicarbonate, calcium, phosphorus and ammonium nitrogen) and
      trophic indices and between them and abundance and richness. Trophic indices and
      McIntosh's index appeared to be more effective in predicting water quality than
      diversity indices. Diversity indices do not necessarily provide any direct
      information on the quality or degree of degradation of the environment from which
      the sample was taken, whereas trophic indices do.

PMID- 12230207
TI  - Removal of free and chelated Cu(II) ions from water by a nondispersive solvent
      extraction process.
AB  - The possibility of extraction of free and the ethylenediaminetetraacetic acid
      (EDTA)-chelated Cu(II) ions from water through a microporous hollow fiber to an
      organic phase containing extractants LIX64N and Aliquat 336 (a quaternary amine)
      was studied, in which Cu(II) was simultaneously back-extracted across another
      hollow fiber to a stripping solutions containing HCl. Experiments were carried
      out at different flow rates of feed (1.4-4.3 cm3/s), organic (1.2-4.1 cm3/s), and
      stripping phases (1.4-4.3 cm3/s), and temperatures (298-318 K). It was shown that
      the extraction rate increased with decreasing feed phase flow rate, but the
      effect of flow rates of organic and stripping phases was not pronounced under the
      ranges studied. Mechanism of the mass transfer at each step was discussed and the
      effect of mutual interaction of the two extractants in the organic phase was also
      examined. The application potentials of this novel extraction process for this
      subject appeared to be technically promising.

PMID- 12230209
TI  - Fates of bacteriophages and bacterial indicators in the Moselle river (France).
AB  - It has been suggested that bacteriophages can provide useful information about
      the pathogenic microorganisms, particularly enteric viruses, present in water.
      This information is complementary to that obtained from bacterial indicators of
      faecal contamination, which would be of great value for evaluating the risks
      associated with the use of certain types of water. Before bacteriophages can be
      used as indicators of faecal contamination, we need to confirm that
      bacteriophages give a different response to that given by the well-known bacteria
      indicators and to determine what happens to bacteriophages in river water.
      Indeed, drinking water is often produced from river water, either by natural
      filtration through the soil or after undergoing various treatments. We collected
      96 river water samples from six different sites between February and November
      2000. The samples were analysed for three faecal indicator bacteria
      (thermotolerant coliforms, enterococci and spores of sulphite-reducing anaerobes)
      and three types of bacteriophages (somatic coliphages, F-specific phages and
      Bacteroides fragilis phages). The densities of thermotolerant coliforms and
      enterococci depended mainly on physical factors such as flow rate and water
      temperature. High temperature and low flow rate led to a decrease in the density
      of these microorganisms, especially in the absence of a major input of faecal
      pollution. Conversely, the densities of somatic coliphages, F-specific phages and
      spores of sulphite-reducing anaerobes remained constant regardless of the flow
      rate and temperature. The density of Bacteroides fragilis phages was too low for
      unambiguous determination of their fate in river water.

PMID- 12230208
TI  - Effect of influent organic content on digested sludge extracellular polymer
      content and dewaterability.
AB  - The organic composition of the feed sludge to six laboratory-scale anaerobic
      digesters was adjusted by substituting a proportion of the primary sludge for
      glucose or propionic acid solution. Substitution with glucose caused an increase
      in the microbial extracellular polymer (ECP) content of the digested sludge,
      which altered the particle size distribution of the sludge and made the sludge
      more difficult to dewater. Substitution with propionic acid gave similar results
      to the control. The relationship between the digested sludge extracted ECP yield
      and sludge filtrability determined using the capillary suction time test was
      significant at the P = 0.01 level. The level of ECP for optimum sludge
      dewaterability was calculated as 17.2 mg g(-1) SS. The protein and carbohydrate
      composition of the extracted polymer did not appear to affect the sludge
      dewaterability. Results present will allow predictions to be made into the effect
      that changes in the influent sewage composition has on essential downstream
      processes.

PMID- 12230210
TI  - Kinetics of the oxidation of methyl tert-butyl ether (MTBE) by potassium
      permanganate.
AB  - The occurrence of the fuel oxygenate methyl tert-butyl ether (MTBE) in the
      environment has received considerable scientific attention. The pollutant is
      frequently found in the groundwater due to leaking of underground storage tanks
      or pipelines. Concentrations of more than several mg/L MTBE were detected in
      groundwater at several places in the US and Germany in the last few years. In
      situ chemical oxidation is a promising treatment method for MTBE-contaminated
      plumes. This research investigated the reaction kinetics for the oxidation of
      MTBE by permanganate. Batch tests demonstrated that the oxidation of MTBE by
      permanganate is second order overall and first order individually with respect to
      permanganate and MTBE. The second-order rate constant was 1.426 x 10(-6) L/mg/h.
      The influence of pH on the reaction rate was demonstrated to have no significant
      effect. However, the rate of MTBE oxidation by potassium permanganate is 2-3
      orders of magnitude lower than of other advanced oxidation processes. The slower
      rates of MTBE oxidation by permanganate limit the applicability of this process
      for rapid MTBE cleanup strategies. However, permanganate oxidation of MTBE has
      potential for passive oxidation risk management strategies.

PMID- 12230211
TI  - Treatment of perchlorate- and nitrate-contaminated groundwater in an autotrophic,
      gas phase, packed-bed bioreactor.
AB  - The biological degradation of perchlorate was examined using a laboratory-scale,
      autotrophic, packed-bed biofilm reactor. The reactor was operated in unsaturated
      flow mode and continuously fed water containing perchlorate (ClO4-) (as an
      electron acceptor), and a gas mixture of hydrogen (5%) and carbon dioxide at a
      retention time of 1.5 min. In the absence of nitrate, perchlorate removal rate
      (rp, ppb/min) in the reactor was found to be first order with respect to
      perchlorate concentration (c, ppb) according to rp = 0.16 +/- 0.06c(0.97+/-0.12)
      (n = 11, R2 = 0.97, p < 10(-5)). Perchlorate removal rates in the hydrogen feed
      were found to be comparable to rates found by others for fixed film bioreactors
      using either hydrogen gas or organic electron donors such as acetate, although
      the rate coefficient was reduced to slightly less than unity (r(p) = 0.22 +/-
      0.08c(0.91+/-0.08); n = 19, R2 = 0.89, p < 10(-5)). When nitrate was present in
      the water, similar perchlorate removals were achieved despite nitrate
      concentrations three orders of magnitude higher than perchlorate concentrations.
      Perchlorate was removed by an average of 25 +/- 5% from a perchlorate
      contaminated groundwater containing 73 +/- 2 ppb of perchlorate and 21 +/- 2 ppm
      of nitrate. This removal was slightly higher than the removal of 17 +/- 3%
      measured for a synthetic groundwater containing 79 +/- 3 ppb of perchlorate and
      22 +/- 2 ppm of nitrate. In both cases, there was an average of 10% nitrate
      removal.

PMID- 12230212
TI  - Field transfer of periphytic diatom communities to assess short-term structural
      effects of metals (Cd, Zn) in rivers.
AB  - Short-term effects of metal pollution were assessed by transferring periphytic
      diatom communities developed on artificial substrates from a reference site to a
      site polluted by heavy metals (around 15 microg Cd L(-1) and 800 microg Zn L(
      1)), located in neighbouring streams. Metal sensitivity of mature assemblages
      (aged 1 month) was evaluated by studying changes in diatom density and taxonomic
      composition 2 and 4 weeks after the transfer. Resident communities of both sites
      were simultaneously collected on similar artificial substrates, in order to
      compare short-term effects of metals within transferred communities with long
      term effects observed at the polluted site. Field transfer induced a marked shift
      of community structure towards that of the resident community of the polluted
      site: diatom density rapidly decreased after the transfer, from 35,000+/-4000 to
      15,000+/-300 cells cm(-2) after 2 weeks, and taxonomic composition changed.
      Relative abundances of species characteristic of the reference site rapidly
      decreased, e.g. Nitzschia dissipata and Gomphoneis minuta, whereas species
      characteristic of the polluted site progressively increased within transferred
      communities, e.g. Gomphonema parvulum, Pinnularia sp. or Fragilaria crotonensis.
      The structure of periphytic diatom communities could therefore be an indicator of
      metal pollution, with marked taxonomic changes being identified within reference
      assemblages after only 2 weeks under relatively low metal exposure.

PMID- 12230213
TI  - Decomposition of trihaloacetic acids and formation of the corresponding
      trihalomethanes in drinking water.
AB  - The decomposition of trihaloacetic acids [bromodichloroacetic acid (BDCAA),
      dibromochloroacetic acid (DBCAA), tribromoacetic acid (TBAA)], and the formation
      of the corresponding trihalomethanes [bromodichloromethane (BDCM),
      dibromochloromethane (DBCM), tribromomethane (TBM)] were studied. Like TBAA, the
      two mixed chlorobromo-species, BDCAA and DBCAA, were found to decompose to form
      BDCM and DBCM, respectively, via a decarboxylation pathway. The decomposition of
      BDCAA, DBCAA and TBAA in water at neutral pH follows a first-order reaction, with
      rate constants of 0.0011, 0.0062 and 0.040 day(-1) at 23 degrees C, respectively;
      and 0.000028, 0.00014 and 0.0016 day(-1) at 4 degrees C, respectively. The
      activation energies for the decomposition reaction of BDCAA, DBCAA and TBAA in
      water at neutral pH were found to be 35.0, 34.5 and 29.2 kcal/mol, respectively.
      The effect of pH in the range of 6-9 and the effect of a drinking water matrix on
      the decomposition of BDCAA, DBCAA, and TBAA in water were found to be
      insignificant. Measurement and health implications due to decomposition of
      trihaloacetic acids and formation of the corresponding trihalomethanes were
      discussed. By applying the technique of quantitative structure-activity
      relationships (QSAR), the decomposition rate constants of six iodinated
      trihaloacetic acids were estimated.

PMID- 12230214
TI  - A review of nucleic acid-based diagnostic tests for systemic mycoses with an
      emphasis on polymerase chain reaction-based assays.
AB  - Nucleic acid-based assays have good potential to complement and enhance the
      sensitivity and rapidity of conventional methods used in diagnostic mycology. The
      majority of molecular tests are polymerase chain reaction (PCR)-based assays
      focusing mainly on the detection of Candida and Aspergillus spp. from clinical
      samples. DNA extraction and purification procedures should be standardized and
      can be facilitated by using commercial extraction kits. In general, protocols
      that target multi-copy genes provide the greatest sensitivity. Objective endpoint
      assessments of PCR tests using enzyme-linked immunosorbent assays (ELISA) or
      commercial quantitative systems are capable of rapidly detecting and identifying
      Candida and Aspergillus spp. Sequencing of PCR products can be used to confirm
      the identity of amplicons. In cases of suspected invasive aspergillosis, PCR
      should be performed on both blood and bronchoalveolar lavage fluid to maximize
      test sensitivity and the positive predictive value. At least two blood specimens
      should be tested if PCR is undertaken on blood samples alone. In situ
      hybridization techniques have been used with success to identify fungi in tissue
      specimens. The wide application of PCR-based assays relies on the introduction of
      standardized protocols following their evaluation in multicentre, prospective
      studies.

PMID- 12230215
TI  - Distinct protective host defenses against oral and vaginal candidiasis.
AB  - Oral and vaginal candidiasis are the two most common forms of opportunistic
      fungal infections. However, the prevalence of each can be quite variable
      depending on the immune status of the host. While vulvovaginal candidiasis (VVC)
      is equally common in immunocompetent and immunocompromised women, oropharyngeal
      candidiasis (OPC) is infrequent except under immunocompromised states. Candida
      albicans, the causative agent in the majority of cases, is a commensal of the
      gastrointestinal and lower female reproductive tracts. Thus, most healthy
      individuals have protective Candida-specific immunity that normally prevents
      infection. Studies from animal models, women with recurrent VVC (RVVC) and HIV
      infected individuals, however, suggest that distinct protective host defense
      mechanisms may function against OPC and VVC. While local and systemic cell
      mediated immunity (CMI) appear important for protection against OPC, there is
      little evidence to indicate that either local or systemic CMI plays a role
      against VVC. Innate resistance is also considered distinct at both sites with
      considerably less activity at the vaginal mucosa, including the newfound anti
      Candida activity by epithelial cells. Finally, the protective role of humoral
      immunity has been and remains uncertain. Taken together, the differential
      prevalence of VVC and OPC is directly proportional to the levels of demonstrable
      innate and adaptive host defenses at each site.

PMID- 12230216
TI  - Role of Paracoccidioides brasiliensis cell wall fraction containing beta-glucan
      in tumor necrosis factor-alpha production by human monocytes: correlation with
      fungicidal activity.
AB  - The polysaccharide fraction of Paracoccidioides brasiliensis mycelial cell wall
      (F1 fraction), the active component of which is composed of beta-glucan, was
      investigated in regard to the activation of human monocytes for fungal killing.
      The cells were primed with interferon-gamma (IFN-gamma) or F1 (100 and 200 microg
      ml(-1)) or F1 (100 and 200 microg ml(-1)) plus IFN-gamma for 24 h and then
      evaluated for H2O2 release. In other experiments, the cells were pretreated with
      the same stimuli, challenged with a virulent strain of P. brasiliensis and
      evaluated for fungicidal activity and levels of tumor necrosis factor (TNF-alpha)
      in the supernatants. F1 increased the levels of H2O2 in a similar manner to IFN
      gamma. However, a synergistic effect between these two activators was not
      detected. On the contrary, a significant fungicidal activity was only obtained
      after priming with IFN-gamma plus F1. This higher activity was associated with
      high levels of TNF-alpha in the supernatants of the cocultures. Overall, P.
      brasiliensis F1 fraction induced human monocytes to release relatively high
      levels of TNF-alpha, which, in combination with IFN-gamma, is responsible for the
      activation of human monocytes for effective killing of P. brasiliensis.

PMID- 12230217
TI  - High rate of vaginal infections caused by non-C. albicans Candida species among
      asymptomatic women.
AB  - A prospective observational study of patients attending a gynecological clinic
      and those referred to a clinic for genitourinary infections was undertaken with
      the purpose of evaluating the relative prevalence of non-C. albicans Candida
      species among Candida isolates from the vagina in different clinical settings in
      an area with high occurrence of vulvovaginal candidiasis. The rate of non-C.
      albicans Candida species was 44.5% among asymptomatic women, 19.4% among those
      with sporadic vaginitis and 21% among patients with chronic vaginal symptoms (p <
      0.001 for asymptomatic vs. pooled symptomatic women). No increase in the rate of
      non-C. albicans Candida was observed during a period of 4 years (1995-1998)
      despite a 1.57-fold increase in the sales of azole antifungal agents. Unlike some
      previous reports we could not document an association of non-C. albicans Candida
      species with chronic vaginal symptoms or increased use of azole antifungal
      agents. The significantly higher rate of these yeasts in asymptomatic women is in
      accord with the known tendency of non-C. albicans Candida species to cause mild
      symptoms.

PMID- 12230218
TI  - Paracoccidioides brasiliensis-reactive antibodies in Brazilian blood donors.
AB  - In a survey for primary paracoccidioidomycosis (PCM) infection (and not the
      clinical disease), two groups of blood donors were analyzed. One study group was
      drawn from donors living in a rural area where PCM is endemic, and the other
      group from urban residents of a large city, Sao Paulo. Anti-Paracoccidioides
      brasiliensis (Pb) specific antibodies (IgG) in sera were analyzed by ELISA, using
      crude Pb exoantigens (exoAg) and purified specific Pb 43 kDa glycoprotein (gp43).
      The results showed that 21% of 700 rural samples and 0.9% of 350 urban samples
      were positive for exoAg and gp43. To avoid cross-reactions, the sera were
      adsorbed first with Histoplasma capsulatum antigens and secondly with Leishmania
      amazonensis antigens. In the first adsorption with H. capsulatum, reactivity to
      gp43 fell to 12.8% in the rural group and to 0% in the urban group. In the
      succeeding adsorption with L. amazonensis, this reactivity fell to 12.3% in the
      rural group. There was a statistically greater proportion of persons with gp43
      reactive antibodies in rural group than in the urban group, indicating that rural
      residents had frequently become exposed to Pb and contracted primary, subclinical
      PCM. The present report is the first epidemiological study using ELISA to detect
      antibodies against gp43 in blood donors.

PMID- 12230220
TI  - Fusarium dimerum as a cause of human eye infections.
AB  - Fusarium dimerum, typically a soil fungus, was isolated from an adult male
      suffering from a corneal ulcer following an injury to the eye. This fungus has
      not been described to cause human infections in South Africa and has not been
      recorded from soil, plant or organic material in this country. The macro- and
      microscopic characteristics of the isolate were found to be indistinguishable
      from described strains. Its authenticity was confirmed by comparing it to other
      human isolates from the eye obtained in the USA, thus rendering this the first
      report of F. dimerum from an eye infection in a human in South Africa.

PMID- 12230219
TI  - Phagocytic and candidacidal activities of macrophages from suckling and adult
      mice pretreated with concanavalin-A.
AB  - In this study, we investigated the effect of concanavalin-A (Con-A) on the
      activation of phagocytosis and killing of Candida albicans by peritoneal
      macrophages from suckling and adult mice. Pretreatment of adult mice with Con-A
      dose-dependently increased the percentage of macrophages phagocytosing C.
      albicans in vitro from 3.8 +/- 0.9 to 24.2 +/- 2.4 in the absence of serum
      opsonins. Addition of mannan (50 microg) and mannose (50 mM) to the incubation
      medium reduced phagocytosis from 21.5 +/- 1.3 to 4.7 +/- 1.9, suggesting that
      treatment with Con-A increased phagocytosis mediated by mannose receptors.
      Killing of C. albicans was also increased by increasing the dose of Con-A.
      Pretreatment of suckling mice with Con-A increased the macrophages' phagocytic
      and candidacidal activities by an amount similar to that observed in adult mice.
      Furthermore, suckling mice pretreated with Con-A survived an intraperitoneal
      inoculum of 5 x 10(7) C. albicans, whereas all control mice died within 24-48 h
      of infection. This suggested that increased phagocytosis and killing of C.
      albicans stimulated by the action of Con-A conferred early protection upon
      suckling mice experimentally infected with C. albicans.

PMID- 12230221
TI  - Correlation of factor XIIIa+ dermal dendrocytes with paracoccidioidomycosis skin
      lesions.
AB  - We demonstrated and quantified by immunohistochemistry the factor XIIIa+ dermal
      dendrocytes (FXIIIa+ DD) in paracoccidioidomycosis skin lesions. Sixty-one
      biopsies were classified according to the tissue response in well-organized
      granulomas (group 1), poorly organized granulomas (group 2) and samples showing
      both kinds of granuloma (group 3). Ten biopsies from normal skin were used as
      controls. In order to verify the internalization of Paracoccidioides brasiliensis
      antigens by FXIIIa+ DD, we performed a double immunostaining technique. FXIIIa+
      DD were hypertrophied with prominent dendrites and their number in the test
      groups was higher than in the control group, especially in the dermal papillae.
      P. brasiliensis yeasts were seen within the cytoplasm of FXIIIa+ DD in 40% of the
      immunostained biopsies. We could correlate these findings with the probable role
      of FXIIIa+ DD as antigen-presenting cells in the pathogenesis of skin lesions in
      paracoccidioidomycosis.

PMID- 12230223
TI  - Unusual presentation of Microsporum canis in human hair.
AB  - This study reports an unusual presentation of Microsporum canis in infected human
      hair in a three-year-old boy. Infected hairs showed ectothrix colonization with a
      mass of small conidia and numerous macroconidia typical of the genus Microsporum.
      The infected hairs also showed strong invasion by hyphae bearing small numbers of
      arthroconidia. These hyphae were thinner and longer than those normally found in
      hair and scalp. It is well known that in cases of tinea capitis due to M. canis,
      ectothrix arthroconidia formation is extrapilary and arises from intrapilary
      hyphae. In this case it seems that unusual quantities of hyphae were formed, and
      not all of them broke down into arthroconidia. They appeared to remain in the
      hair and to produce macroconidia, which were not formed outside the hair in
      contact with air, but instead seemed to remain in a deeper layer of the hair than
      the arthroconidia seen.

PMID- 12230222
TI  - Randomized trial with itraconazole, ketoconazole and sulfadiazine in
      paracoccidioidomycosis.
AB  - Forty-two patients with active paracoccidioidomycosis were randomized to receive
      itraconazole (50-100 mg d(-1)), ketoconazole (200-400 mg d(-1)) or sulfadiazine
      (100-150 mg kg d(-1) up to 6 g d(-1)) for 4-6 months, followed by slow release
      sulfa until negativity of serological tests. All 14 patients in itraconazole and
      sulfadiazine groups and 13 in the ketoconazole group showed an adequate clinical
      response to the chemotherapy. One patient in the latter group showed treatment
      failure according to clinical and mycological criteria. The test of the
      hypothesis that the drugs reduced antibody levels up to ten months of treatment
      showed a p value equal to 0.0001 for itraconazole, 0.017 for ketoconazole and
      0.0012 for sulfadiazine; this reduction was similar for the three groups. In this
      first randomized study for the treatment of paracoccidioidomycosis we could not
      show superiority of any one regimen over the others in the clinical and
      serological responses of patients with the moderately severe form of the disease.

PMID- 12230224
TI  - Localized lymphatic sporotrichosis after fish-induced injury (Tilapia sp.).
AB  - Localized lymphatic sporotrichosis generally develops after the fungus Sporothrix
      schenckii is traumatically introduced into skin or mucosa by contaminated plant
      material. An 18-year-old male fisherman was injured by spines of the dorsal fin
      of a fish on the left third finger. The lesion became ulcerated, edematous and
      suppurative and did not respond to tetracycline and cephalexin. Fifteen days
      after the accident, a nodular lymphangitic pattern of swelling was observed.
      Histopathological findings and an intradermal test were suggestive of
      sporotrichosis and mycological cultures confirmed the diagnosis. The lesions
      resolved after oral treatment with potassium iodide. Sporotrichosis is a common
      subcutaneous mycosis in Brazil, and there is a previous report in the literature
      of this disease being acquired via trauma involving fish spines.

PMID- 12230225
TI  - Additional case of Ramichloridium mackenziei cerebral phaeohyphomycosis from the
      Middle East.
AB  - In this report we describe a case of cerebral phaeohyphomycosis involving a 56
      year-old Egyptian male who worked as a mason in Kuwait for 6 years. Computerized
      tomography scan of the brain revealed presence of a large abscess in the left
      occipital lobe. Aspirated pus from the abscess showed branched, septate, hyphae
      with light brown pigmentation. Cultured pus grew the fungus Ramichloridium
      mackenziei. Despite amphotericin B (1 mg kg(-1) per day) therapy for 2 weeks, the
      patient expired. The isolate was later found to be resistant to amphotericin B (
      > 32 microg ml(-1)). Antifungal susceptibility testing to other agents was also
      performed.

PMID- 12230226
TI  - Isolation of Fusarium solani from a dog: identification by molecular analysis.
AB  - A strain of Fusarium solani was isolated from a dog showing many cutaneous and
      submucosal nodules and pyogranulomatous kidney lesions. Clinical isolates from
      this systemic infection were identified using microscopic examination and
      confirmed by molecular analysis.

PMID- 12230227
TI  - Molecular identification of Trichophyton rubrum isolate from a dog by chitin
      synthase 1 (CHS1) gene analysis.
AB  - A nonsporulating isolate from a dog with dermatophytosis was identified as
      Trichophyton rubrum by molecular analysis. The nucleotide sequence analysis of
      the chitin synthase 1 (CHS1) gene from the isolate indicated more than 99%
      sequence similarity with other human and canine isolates of T rubrum. The
      molecular typing suggested that isolates of T. rubrum from human and canine
      sources were genetically identical.

PMID- 12230228
TI  - Prevalence of Candida dubliniensis in the BCCM/IHEM Biomedical Fungi/Yeasts
      culture collection (isolates before 1990).
AB  - The BCCM/IHEM Biomedical Fungi/Yeasts collection hosts 1200 Candida albicans
      strains of the Vanbreuseghem mycotheque isolated between 1951 and 1997. From this
      collection, 469 freeze-dried C. albicans strains, producing chlamydospores, germ
      tubes and forming green colonies on CHROMagar, all isolated before 1990, were
      screened to identify the Candida dubliniensis isolates. Screening was performed
      in different steps using the growth at 45 degrees C, the assimilation of xylose,
      the intracellular beta-glucosidase activity test and C. dubliniensis-specific
      polymerase chain reaction (PCR) with primers from ACT1 intron sequence. Five
      isolates (1%) were identified as C. dubliniensis: one isolate was not documented,
      the others were of oropharyngeal origin of which two (1987 and 1990) were from
      proven human immunodeficiency virus patients.

PMID- 12230229
TI  - Iron status and dietary intake of Chinese pregnant women with anaemia in the
      third trimester.
AB  - Anaemia in pregnancy is a major public health problem in China. Anaemia in
      pregnant women may be related to dietary intake of nutrients. To examine the
      relationship between iron status and dietary nutrients, a cross-sectional study
      in pregnant women was carried out. The intake of foods and food ingredients were
      surveyed by using 24-h dietary recall. Blood haemoglobin, haematocrit, serum
      iron, serum ferritin, transferrin and soluble transferrin receptor were measured
      in 1189 clinically normal pregnant women in the third trimester of pregnancy. The
      results showed that the average daily intake of rice and wheat was 504.2 g in the
      anaemia group and 468.6 g in the normal group. Carbohydrates accounted for 63.69%
      and 63.09% of energy in the anaemia and normal groups, respectively. Intake of
      fat was very low; 18.38% of energy in anaemia group and 19.23% of energy in
      normal group. Soybean intake was 109.4 g/day and 63.6 g/day in the anaemia and
      normal groups, respectively (P < 0.001). There were lower intakes of green
      vegetables (172.1 g/day) and fruits (154.9 g/day) in the anaemia group than in
      the normal group (246.2 g/day green vegetables (P < 0.001) and 196.4 g/day fruit
      (P < 0.001)). Intakes of retinol and ascorbic acid were much lower in the anaemia
      than in the normal group (P < 0.001). In the anaemia group, vitamin A intake was
      only 54.76% of the Chinese recommended daily allowance (RDA) and ascorbic acid
      intake was 53.35% of the Chinese RDA. Intake of total vitamin E was 14.55 mg/day
      in the anaemia group compared with 17.35 mg/day in the normal group (P < 0.016).
      Moreover, intake of iron in pregnant women with anaemia was slightly lower than
      that in the normal group. Comparison of iron status between the anaemia and
      normal groups found serum iron in women with anaemia at 0.89 microg/L, which was
      significantly lower than 1.09 microg/L in the normal group (P < 0.001). There
      were lower average values of ferritin (14.70) microg/L) and transferrin (3.34
      g/L) in the anaemia group than in the normal group (20.40 microg/L ferritin (P <
      0.001) and 3.44 g/L transferrin (P < 0.001)). Soluble transferrin receptor was
      significantly higher (32.90 nmol/L) in the anaemia than in the normal group
      (23.58 nmol/L; P < 0.001). The results of this study indicate that anaemia might
      be attributed to a low iron intake, a low intake of enhancers of iron absorption
      and a high intake of inhibitors of iron absorption from a traditional Chinese
      diet rich in grains.

PMID- 12230230
TI  - Faecal bulking efficacy of Australasian breakfast cereals.
AB  - Faecal bulk may play an important role in preventing a range of disorders of the
      large bowel, but as yet there is little information available on the relative
      faecal bulking capacities of various foods. Breakfast cereals are often promoted
      as a good source of potential bulk for 'inner health' because they provide
      dietary fibre, but their relative abilities to provide faecal bulk per se have
      not been described. The faecal bulking efficacy of 28 representative Australasian
      breakfast cereals was therefore measured. A rat model developed for the purpose,
      and shown to give similar responses as humans to cereal fibres, was used to
      measure faecal bulking efficacy as increases in fully hydrated faecal weight/100
      g diet, based on precise measurements of food intake, faecal dry matter output
      and faecal water-holding capacity (g water held without stress/g faecal dry
      matter). Compared to a baseline diet containing 50% sucrose, increments in
      hydrated faecal weight due to 50% breakfast cereal ranged from slightly negative
      (Cornflakes, -2 g/100 g diet) to about 80 g/100 g diet (San Bran). Most breakfast
      cereals increased hydrated faecal weight by between 10 and 20 g/100 g diet from a
      baseline of 21 +/- 1.5 g/100 g diet, but four products containing high levels of
      wheat bran had an exceptionally large impact on hydrated faecal weight (increment
      > 20 g/100 g diet), and the changes resulted more from relative changes in dry
      matter output than in faecal water retention/gram. However, as faecal water
      retention was about 2.5 g water/g faecal dry matter on average, increases in dry
      matter represented large increases in faecal water load. Faecal bulking indices
      (FBI) for most of the breakfast cereals were less than 20 (wheat bran = 100). The
      content of wheat bran equivalents for faecal bulk (WBE(fb)) in the breakfast
      cereals was calculated from FBI. Most breakfast cereals contributed, per serve,
      less than 10% of a theoretical daily reference value for faecal bulk (DRV(fb) =
      63 WBE(fb)/day), which was based on data from human clinical trials and dietary
      fibre recommendations. Based on the WBE(fb) contribution/serving that would be
      required to meet the DRV(fb) from the number of servings of dietary fibre sources
      in the CSIRO 12345+ food and nutrition plan, the results suggest that although
      some high bran breakfast cereals may contribute substantially to, and many are
      reasonable sources of, faecal bulk, for most of them, one or two servings at
      breakfast cannot be relied on to effectively redress shortfalls in faecal bulk
      elsewhere in the diet.

PMID- 12230231
TI  - Zinc and iron status during pregnancy of Filipino women.
AB  - Low birthweight is associated with maternal anaemia and, in some circumstances,
      with low iron and zinc status, but this relationship has not been investigated in
      the Philippines. In this study, we assessed the prevalence of anaemia and
      suboptimal iron and zinc status in pregnant women from three geographical regions
      (mountain, coast, city) of Zamboanga del Sur province at 24 weeks (n = 305). and
      again at 36 weeks (n = 127), gestation. At 24 weeks, 34% were anaemic (i.e.,
      haemoglobin < 105 g/L) from all causes, of whom only 14% had concomitant low
      serum ferritin values (i.e., < 12 microg/L). The presence of infection was low,
      based on both elevated white blood cell count (> 11 x 10(9)/L; 19%) and serum C
      reactive protein (> 15 mg/L; 3%). Of the women surveyed, 20% were iron depleted
      but not anaemic, and 15% were zinc deficient (i.e., serum zinc < 7.1 Micromol/L).
      The mean (+/- SD) birthweight of the infants (n = 250) was 3074 g +/- 408 g, of
      whom 5% were of low birthweight (< 2500 g). No differences existed for
      biochemical indices or birthweight among the three regions, or between women
      consuming maize or rice-based diets. Women with low haemoglobin (P = 0.05) and
      low serum zinc (P = 0.14) values at 24 weeks gestation had infants with lower
      birthweights than those with values > or = 105 g/L and > or = 7.1 micromol/L,
      respectively. However, in the multivariate model, the contribution of maternal
      haemoglobin to the variance in birthweight at 24 weeks gestation was non
      significant, although modest for serum zinc. Anaemia and/or suboptimal zinc
      status during pregnancy may be related to low birthweight in the Philippines, and
      their aetiology deserves further study.

PMID- 12230232
TI  - Tocotrienols are needed for normal bone calcification in growing female rats.
AB  - In this study the effects of vitamin E deficiency and supplementation on bone
      calcification were determined using 4-month-old female Sprague-Dawley rats. The
      rats weighed between 180 and 200 g. The study was divided in three parts. In
      experiment I the rats were given normal rat chow (RC, control group), a vitamin E
      deficient (VED) diet or a 50% vitamin E deficient (50%VED) diet. In experiment 2
      the rats were given VED supplemented with 30 mg/kg palm vitamin E (PVE30), 60
      mg/kg palm vitamin E (PVE60) or 30 mg/kg pure alpha-tocopherol (ATF). In
      experiment 3 the rats were fed RC and given the same supplements as in experiment
      2. The treatment lasted 8 months. Vitamin E derived from palm oil contained a
      mixture of ATF and tocotrienols. Rats on the VED and 50%VED diets had lower bone
      calcium content in the left femur compared to the RC group (91.6 +/- 13.3 mg and
      118.3 +/- 26.0 mg cf 165.7 +/- 15.2 mg; P < 0.05) and L5 vertebra (28.3 +/- 4.0
      mg and 39.5 +/- 6.2 mg compared with 51.4 +/- 5.8 mg; P < 0.05). Supplementing
      the VED group with PVE60 improved bone calcification in the left femur (133.6 +/-
      5.0 mg compared with 91.6 +/- 13.3 mg; P < 0.05) and L5 vertebra (41.3 +/- 3.3 mg
      compared with 28.3 +/- 4.0 mg; P < 0.05) while supplementation with PVE30
      improved bone calcium content in the L5 vertebra (35.6 +/- 3.1 mg compared with
      28.3 +/- 4.0 mg; P < 0.05). However, supplementation with ATF did not change the
      lumbar and femoral bone calcium content compared to the VED group. Supplementing
      the RC group with PVE30, PVE60 or ATF did not cause any significant changes in
      bone calcium content. In conclusion, vitamin E deficiency impaired bone
      calcification. Supplementation with the higher dose of palm vitamin E improved
      bone calcium content, but supplementation with pure ATF alone did not. This
      effect may be attributed to the tocotrienol content of palm vitamin E. Therefore,
      tocotrienols play an important role in bone calcification.

PMID- 12230233
TI  - Association between overweight or obesity and household income and parental body
      mass index in Australian youth: analysis of the Australian National Nutrition
      Survey, 1995.
AB  - This study is a secondary data analysis based on the 1995 Australian National
      Nutrition Survey (NNS). A random subsample of 1581 school children aged 7-15
      years old from the NNS was studied. The results show the prevalence of
      overweight, obesity and combined overweight and obesity was 10.6-20.9%, 3.7-7.2%
      and 15.6-25.7%, respectively. The odds ratio of overweight or obese boys with
      highest household income was significantly smaller than those with the lowest
      household income. The proportion of combined overweight and obesity in children
      whose parents were overweight or obese was significantly greater compared with
      those whose parents were not. The trend of increasing prevalence of overweight or
      obesity among children with increasing parental body mass index (BMI) was
      significant after adjusting for age except the trend of father's BMI for boys.
      This study provided baseline data on the recent prevalence of overweight or
      obesity of Australian school children using new international absolute BMI cut
      off points. It indicated that young school girls (7-9 years) were more likely to
      be overweight or obese compared with boys, the prevalence rates of overweight or
      obesity in older boys (13-15 year) was significantly greater than in other age
      groups while in girls it was the opposite. The boys with lowest household income
      ($0-17 500) were more likely to be overweight or obese compared with those with
      the highest household income (greater than $67 500). Having parents especially
      mothers who were overweight or obese may increase the risk of children being
      overweight or obese.

PMID- 12230234
TI  - Antioxidant effect of Phaseolus vulgaris in streptozotocin-induced diabetic rats.
AB  - The antioxidant effect of an aqueous extract of Phaseolus vulgaris pods, an
      indigenous plant used in Ayurvedic medicine in India, was studied in rats with
      streptozotocin-induced diabetes. Oral administration of Phaseolus vulgaris pod
      extract (PPEt; 200 mg/kg body weight) for 45 days resulted in a significant
      reduction in thiobarbituric acid reactive substances and hydroperoxides. The
      extract also causes a significant increase in reduced glutathione, superoxide
      dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in the
      liver and kidneys of rats with streptozotocin-induced diabetes. These results
      clearly show the antioxidant property of PPEt. The effect of PPEt at 200 mg/kg
      body weight was more effective than glibenclamide.

PMID- 12230235
TI  - Cross-sectional study of diet and risk factors for metabolic diseases in a
      Ghanaian population in Sydney, Australia.
AB  - Ethnic groups in affluent environments experience higher rates of metabolic
      diseases than their native counterparts. Our objective was to determine the
      prevalence of metabolic risk factors in Ghanaians in Sydney, and to investigate
      the relationship with dietary and lifestyle factors. Cross-sectional design with
      anthropometry, blood pressure, plasma lipids, glucose and insulin concentrations
      were measured on two occasions on each subject. Dietary information was obtained
      by three 24-h dietary recalls. Adults (45 male, 35 female) were recruited from a
      local association in Sydney, Australia. Overweight was observed in a large
      proportion of subjects (71% and 66% of men and women, respectively), with 18% of
      men and 26% of women classified as obese. Abdominal overweight was seen in 63%
      and 74% of men and women, respectively. Abdominal obesity was seen in 20% of men
      and 49% of women. Hypertension was detected in 40% of men and 17% of women, 16%
      of men and 6% of women were diagnosed with definite hypertension. Seventy-one per
      cent of men and 29% of women were classified as hypercholesterolaemic and 67% of
      men and 23% of women had elevated low-density lipoprotein cholesterol. In men,
      low high-density lipoprotein cholesterol and hypertriacylglycerolaemia affected
      18% and 13%, respectively. Fasting hyperinsulinaemia was observed in 14% and 9%
      of men and women, respectively. The majority of subjects (73%) sustained one or
      more metabolic risk factors. Dietary fat contributed 33% and 35% of total energy
      intake in men and women, respectively, saturated fat contributing 11% in both
      sexes. A high prevalence of overweight, diabetes, hypertension and dyslipidaemia
      exists in this population, particularly in men, highlighting the need for
      intervention.

PMID- 12230236
TI  - Glycaemic glucose equivalent: combining carbohydrate content, quantity and
      glycaemic index of foods for precision in glycaemia management.
AB  - The glycaemic index (GI) is the blood glucose response to carbohydrate in a food
      as a percentage of the response to an equal weight of glucose. Because GI is a
      percentage, it is not related quantitatively to food intakes, and because it is
      based on equi-carbohydrate comparisons, GI-based exchanges for control of
      glycaemia should be restricted to foods providing equal carbohydrate doses. To
      overcome these limitations of GI, the glycaemic glucose equivalent (GGE), the
      weight of glucose having the same glycaemic impact as a given weight of food, is
      proposed as a practical measure of relative glycaemic impact. To illustrate the
      differences between GGE and GI in quantitative management of postprandial
      glycaemia, published values for carbohydrate content, GI and serving size of
      foods in the food groupings, breads, breakfast cereals, pulses, fruit and
      vegetables, were used to determine the GGE content per equal weight and per
      serving of foods. Food rankings and classifications for exchanges based on GGE
      content were compared with those based on GI. In all of the food groupings
      analysed, values for relative glycaemic impact (as GGE per 100 g food and per
      serving) within each of the categories, low, medium and high GI were too
      scattered for GI to be a reliable indicator of the glycaemic impact of any given
      food. Correlations between GI and GGE content per serving were highest in food
      groupings of similar carbohydrate content and serving size, including breads (r =
      0.73) and breakfast cereals (r = 0.8), but low in more varied groups including
      pulses (r = 0.66), fruit (r = 0.48) and vegetables (r = 0.28). Because of the non
      correspondence of GI and GGE content, food rankings by GI did not agree with
      rankings by GGE content, and placement of foods in GI-based food exchange
      categories was often not appropriate for managing glycaemia. Effects of meal
      composition and food intake on relative glycaemic impact could be represented by
      GGE content, but not by GI. Because GGE is not restricted to equicarbohydrate
      comparisons, and is a function of food quantity, GGE may be applied, irrespective
      of food or meal composition and weight, and in a number of approaches to the
      management of glycaemia. Accurate control of postprandial glycaemia should
      therefore be achievable using GGE because they address the need to combine GI
      with carbohydrate dose in diets of varying composition and intake, to obtain a
      realistic indication of relative glycaemic impact.

PMID- 12230237
TI  - Green tea catechin improves microsomal phospholipase A2 activity and the
      arachidonic acid cascade system in the kidney of diabetic rats.
AB  - The purpose of this study was to investigate the effects of green tea catechin on
      the microsomal phospholipase A2 activity and arachidonic acid cascade in the
      kidneys of streptozotocin-induced diabetic rats. Sprague-Dawley male rats
      weighing 100 +/- 10 g were assigned randomly to one normal and three
      streptozotocin-induced diabetic groups. The diabetic groups were the DM-0C group
      (n = 10), fed a catechin-free diet, the DM-0.25C group (n = 10), fed a 0.25 g
      catechin per 100 g diet, and the DM-0.5C group (n = 10), fed a 0.5 g catechin per
      100 g diet. The kidney microsomal phospholipase A2 activity was higher in the
      diabetic groups than in the normal group, while it was lower in the DM-0.25C and
      DM-0.5C groups than in the DM-OC group. The percentage of phosphatidylcholine
      hydrolysed in the kidney microsomes was not significantly different between any
      of the four groups. The percentage of phosphatidylethanolamine hydrolysed in the
      kidney microsomes was progressively higher in the DM-0.5C, DM-0.25C and DM-OC
      groups, respectively, compared to the normal group. The formation of thromboxane
      A2 was significantly higher while the formation of prostacyclin was lower in
      kidney microsomes of the streptozotocin-induced diabetic groups compared with the
      normal group, but this condition was improved by catechin supplementation. Kidney
      microsomal vitamin E concentrations were progressively lower in the DM-0.5C, DM
      0.25C, and DM-0C groups, respectively, compared to the normal group. The kidney
      thiobarbituric acid reactive substance (TBARS) contents became higher in the DM
      0C and DM-0.25C groups as compared with the normal group, whereas the DM-0.5C
      group did not differ from the normal group. Kidney function appears to be
      improved by green tea catechin supplementation due to its antithrombus action,
      which in turn controls the arachidonic acid cascade system.

PMID- 12230238
TI  - Effects of green tea catechin on prostaglandin synthesis of renal glomerular and
      renal dysfunction in streptozotocin-induced diabetic rats.
AB  - The purpose of the present study was to investigate the effects of green tea
      catechin on prostaglandin synthesis of renal glomerular and renal dysfunction in
      rats with streptozotocin-induced diabetes. Sprague-Dawley rats weighing 100 +/-
      10 g were randomly assigned to one normal group and three groups with
      streptozotocin-induced diabetes. The diabetic groups were classified to a
      catechin-free diet (DM group), a 0.25% catechin diet (DM-0.25C group) and a 0.5%
      catechin diet (DM-0.5C group) according to the levels of catechin supplement in
      their diet. The animals were maintained on an experimental diet for 4 weeks. At
      this point, they were injected with streptozotocin to induce diabetes. They were
      killed on the sixth day. The catechin supplementation groups (DM-0.25C, DM-0.SC
      groups) showed a decrease in thromboxane A2 synthesis but an increase in
      prostacyclin synthesis, compared to the DM group. The ratio of
      prostacyclin/thromboxane A2 was 53.3% and 38.1% lower in the DM and DM-0.25C
      groups, respectively, than in the normal group. The ratio in the DM-0.5C group
      did not differ from that in the normal group. The glomerular filtration rate in
      catechin feeding groups (DM-0.25C and DM-0.5C groups) was maintained at the
      normal level. The urinary beta2-microglobulin content in the DM-0.5C group was
      significantly lower than that in the normal group. On the sixth day after
      induction of diabetes, the urinary microalbumin content in the DM, DM-0.25C and
      DM-0.5C groups had increased 5.40, 4.02, 3.87 times, respectively, compared with
      the normal group. In conclusion, kidney function appears to be improved by green
      tea catechin supplementation due to its antithrombotic action, which in turn
      controls the arachidonic acid cascade system.

PMID- 12230239
TI  - Selective feeding centres in refugee settings: evaluation framework protocol.
AB  - Selective feeding programs are centres for the treatment of persons suffering
      from acute malnutrition. Unlike chronic malnutrition, acute malnutrition reflects
      recent problems. In a crisis situation, wasting is preferred above other
      indicators because it is sensitive to rapid change, indicates present change, can
      be used to monitor the impact of interventions and is a good predictor of
      immediate mortality risk. This paper reviews the current approach being used in
      the field to evaluate the effectiveness of feeding programs. There is no
      comprehensive evaluation framework in place to assess the impact of feeding
      programs on mortality due to malnutrition. Some loose outcome measures, such as
      the number of children enrolled in a feeding centre, are being used to determine
      if a feeding centre should continue. In addition, malnutrition prevalence and
      crude mortality rates determined through nutritional and mortality surveys are
      used to assess the impact of feeding programs. This procedure does not take into
      account potential confounding factors that impact on malnutrition prevalence,
      including access to non-relief foods and the general food ration. Therefore, one
      could not confidently say that the reduction of malnutrition prevalence is a
      result of feeding programs. This paper presents an alternative approach to
      evaluating feeding centres.

PMID- 12230240
TI  - Determination of the content of desmopressin in pharmaceutical preparations by
      HPLC and validation of the method.
AB  - The aim of this study was to apply high performance liquid chromatography to the
      determination of content of desmopressin in pharmaceutical preparations and
      validation of the method. The satisfactory results have been obtained using a
      column Luna C 8.5 microm, 100 x 4.6 mm and a mobile phase containing 0.067 M
      phosphate buffer of pH = 7 and acetonitrile in the proportion 83:17. It has been
      shown that the elaborated method shows good precision and accuracy and can be
      applied to the qualitative and quantitative analysis of pharmaceutical
      preparations containing desmopressin.

PMID- 12230241
TI  - Acidimetric titration of medicines being salts of weak acids and determining the
      end-point based on the iodate(V)-iodide reaction.
AB  - A sample being a salt of weak acid in a solvent is determined with hydrochloric
      acid in the presence of iodate, iodide and starch. The excess acid colours the
      solution blue.

PMID- 12230242
TI  - Naproxen ion-selective electrode and its application to pharmaceutical analysis.
AB  - An ion-selective membrane electrode was prepared based on ion-pair complex of
      naproxen with methyltrioctylammonium. Its basic analytical parameters such as:
      slope characteristics, measuring range, detection limit, response time, life time
      were determined. The electrode showed Nernstian response from the 10(-1) to 10(
      4) mol l(-1) concentration range and 5.5-8.5 pH range, low limit of detection 5 x
      10(-5) mol l(-1) and short response time--20s. Selectivity was good over a number
      of organic and inorganic anions. The electrode was applied for the determination
      of naproxen tablets in aqueous solutions by the calibration curve method and
      standard addition method.

PMID- 12230243
TI  - Saline cathartics and adsorptive capacity of activated charcoal for doxycycline.
AB  - The effects of sodium chloride and sodium citrate on the in vitro adsorption of
      doxycycline to activated charcoal have been studied. Solutions of doxycycline
      alone and doxycycline with 7.5 mg/ml cathartic solutions were vortex-mixed for 30
      s with different quantities of activated charcoal, incubated for 30 min at 37
      degrees C and analyzed for free doxycycline spectrophotometrically at 348 nm.
      Addition of NaCl had a significant (p<0.05) increase while sodium citrate
      produced a significant (p<0.05) decrease in the adsorption of doxycycline on
      activated charcoal. In all, the adsorption doxycycline on activated charcoal
      obeyed quantity-dependent kinetics.

PMID- 12230244
TI  - Biopharmaceutical assessment of eye drops containing aloe (Aloe arborescens
      Mill.) and neomycin sulphate.
AB  - The subject of the studies was eye drops made of aloe, containing the group of
      aloe chemical substances of anti-inflammatory use and neomycin sulphate. The aim
      of the studies was to evaluate the permeability of biologically active aloe
      substances, determined as aloenin, through synthetic lipophilic and hydrophilic
      membranes in a standard perfusion apparatus and in vitro verification of the
      transport possibilities of these substances through the isolated cornea of pig's
      eye. The permeability process of biologically active aloe substances determined
      as aloenin, through synthetic lipophilic and hydrophilic membranes, was analyzed
      using the first-order kinetics. Estimated quotas of permeability rate constant
      show that the investigated chemical compounds of aloe, included in the eye drops,
      diffused through the applied membranes. The studies of permeability through
      isolated pig's cornea proved that biologically active aloe substances could not
      overcome this biological barrier. On the basis of biopharmaceutical studies it
      can be concluded that the eye drops containing aloe and neomycin sulphate, due to
      the lack of permeating abilities through the eye cornea, should be particularly
      useful in the treatment of inflammations and infections of external parts of the
      eye, such as conjuctiva, eyelid edges, lacrimal sac and cornea.

PMID- 12230245
TI  - The effect of cryoprotectants on the physical properties of large liposomes
      containing sodium diclofenac.
AB  - Large liposomes (1-10 microm) containing sodium diclofenac were prepared and
      lyophilized using lactose or mannitol (7.5% in respect to the lipid content) as
      cryoprotectants. The physical studies of liposomes were performed during 30 days
      of storage in a dry or resuspended form. Lyophilization of large liposomes and
      storage in the dry form at 5 degrees C increases their physical stability.
      Lactose is a cryoprotectant which does not influence changes of properties of
      liposomes regarding their size, encapsulation efficacy and release rate. Large
      liposomes lyophilized in the presence of mannitol tend to increase in size and
      encapsulation efficacy, but the lipid bilayers are stabilized and less permeable
      to the drug.

PMID- 12230246
TI  - Mechanism of in vitro release kinetics of flurbiprofen loaded ethylcellulose
      micropellets.
AB  - Flurbiprofen loaded ethylcellulose micropellets with different drug loading were
      prepared by a quasi-emulsion solvent diffusion technique. Encapsulation
      parameters of micropellets such as actual drug loading, drug encapsulation
      efficiency (DEE) and loss of coating polymer (LCP) were determined. Actual drug
      loading was increased with the increased initial drug loading whereas
      encapsulation efficiency decreased with the increase of actual drug loading. In
      vitro drug release profiles of these micropellets were evaluated in distilled
      water (DW) and also in phosphate buffer solution (PBS) to indicate pH dependency
      release rates. All the batches of micropellets released about 35-59% in DW and 89
      97% in PBS during the period of 8 h and the burst effect of about 50-75% in the
      first 1.5 h was seen only in PBS. The mechanism of release kinetics was evaluated
      by fitting the release data to the zero order, first order, Higuchi, Baker
      Lonsdale and Peppas equations and also to the differential forms of zero order,
      first order and Higuchi model. Adequate fitting of release data was found with
      first order, Higuchi and Peppas models and hence these models were selected for F
      test statistics for ascertaining the mechanism of drug release. Higuchi model of
      drug release in DW and PBS of all the formulations was ruled out due to its
      significantly different F-value with other models. Thus, mechanism of release of
      flurbiprofen from ethylcellulose micropellets may be explained by the diffusional
      exponent model of Peppas et al. as ascertained by F-test statistics rather than
      the same, based on some other diffusional models even though they have shown good
      correlation.

PMID- 12230247
TI  - Synthesis of 6-substituted 6H-indolo[2,3-b]quinolines as novel cytotoxic agents
      and topoisomerase II inhibitors.
AB  - A systematic investigation into the impact of the substituents introduced into
      the indolo[2,3-b]quinoline system is described. The findings clearly demonstrate
      that the compounds bearing a methyl group or a longer aliphatic chain at the N-6
      position are inactive against prokaryotic and eukaryotic cells. The introduction
      of alkyl-amino-alkyl substituent at the N-6 position of indolo[2,3-b]quinoline
      accounts for the appearance of the antimicrobial and.cytotoxic properties. The
      cytotoxicity against oral epidermoid carcinoma KB (ID50) is in the range from 2.0
      to 9.0 microM, and the antimicrobial activity (MIC) falls between 0.03 and 0.50
      mM. The structural relation within 6H-indolo[2,3-b]quinolines, concerning their
      antimicrobial and cytotoxic activity, corresponds well with their ability to bind
      DNA and to inhibit topoisomerase II activity.

PMID- 12230248
TI  - Synthesis and anticonvulsant properties of new 1-phenyl and 1-phenylamino-3
      phenylpyrrolidine-2,5-dione derivatives.
AB  - A series of N-aryl and N-aminoaryl 3-phenyl pyrrolidine-2,5-diones were
      synthesized and tested for anticonvulsant activity in the maximum electroshock
      seizure (MES) and pentetrazol seizure threshold (sc Met) tests. Structures of the
      novel compounds were confirmed by elemental and spectral analyses.

PMID- 12230249
TI  - Synthesis and antiproliferative activity in vitro of new 3-substituted
      aminopyrazolo[3,4-b]pyridines.
AB  - The synthesis of several new 3-substituted aminopyrazolo[3,4-b]pyridines is
      described. The obtained compounds were tested for their antiproliferative
      activity in vitro. Two of them: 3-chloroacetylaminopyrazolo[3,4-b]pyridine [II]
      and 3-(2-bromopropionyl-amino)pyrazolo[3.4-b]pyridine [III] revealed cytotoxic
      activity against the cells of 5 human tumor cell lines applied. Their ID50 values
      were in the range of the international activity criterion for synthetic agents (4
      microg/ml). The structures of the products II-XVII were established on the basis
      of elemental analysis and spectral data (IR, 1H NMR and MS).

PMID- 12230250
TI  - Synthesis and antimicrobial activity of 3-hydroxyimino-5-methyl-2-hexanone(HIMH)
      and its dioxime derivative.
AB  - A new oxime, 3-hydroxyimino-5-methyl-2-hexanone (HIMH) has been synthesized by
      the reaction of 1-pentyl nitrite with 5-methyl-2-hexanone under acidic
      conditions. The subsequent treatment of HIMH with NH2OH x HCl gives 5-methyl-2,3
      hexanedione dioxime (H2MHDDO). The structures of these compounds have been
      confirmed by physicochemical and spectral data. A preliminary screening of these
      compounds for biological activity against several microorganisms has indicated
      that they are selective growth inhibitors of m-tuberculosis, in particular.

PMID- 12230251
TI  - Flavonoid compounds in the flowers of Abutilon indicum (L.) Sweet (Malvaceae).
AB  - Seven flavonoid compounds: luteolin, chrysoeriol, luteolin 7-O-beta
      glucopyranoside, chrysoeriol 7-O-beta-glucopyranoside, apigenin 7-O-beta
      glucopyranoside, quercetin 3-O-beta-glucopyranoside, quercetin 3-O-alpha
      rhamnopyranosyl (1 --> 6)-beta-glucopyranoside, were isolated and identified from
      the flowers of Abutilon indicum (L.) Sweet (Malvaceae).

PMID- 12230252
TI  - Evaluation of probucol as suppressor of ceftizoxime induced lipid peroxidation.
AB  - Considering drug induced lipid peroxidation, a possible mediator of drug induced
      toxicity and exploiting free radical scavenging action of probucol, which is a
      synthetic antioxidant of therapeutic interest, in vitro effects of the
      antioxidant on drug induced lipid peroxidation have been studied to explore its
      possible potential in reducing drug induced toxicity. In the present study,
      ceftizoxime sodium, a third generation of cephalosporin, has been taken as the
      representative drug and goat whole blood has been used as the lipid source. The
      study revealed that probucol could suppress drug induced lipid peroxidation to a
      significant extent. This provides scope for further study on probucol to evaluate
      its potential for reducing drug induced toxicity and increasing therapeutic index
      of drug by possible cotherapy.

PMID- 12230253
TI  - Synthesis of new derivatives of 3-methyl-8-aryl-7,8-dihydro-6H-imidazo[2,1
      c][1,2,4] triazin-4-one.
AB  - Cyclocondensation of 1-aryl-2-hydrazinoimidazolines with pyruvic acid furnished
      novel derivatives of imidazo [2,1-c] [1,2,4]triazin-4-one.

PMID- 12230254
TI  - Application of organotypic hippocampal culture for study of selective neuronal
      death.
AB  - The organotypic hippocampal culture model was established according to the
      Stoppini method. The transversal hippocampal slices from 7-day-old Wistar rats
      were cultured 14 days in vitro then subjected to acute metabolic stress induced
      either byglucose deprivation or by additional treatment with a chemical
      respiratory chain inhibitor-cyanide in 3 mM concentration. The rate of cell death
      was monitored up to several hours post-treatment in living tissue by propidium
      iodide staining or by a trypan-blue exclusion test. No signs of selective
      vulnerability of any particular hippocampal region or cellular layers to applied
      metabolic insults were found. Slices demonstrated total resistance even to
      prolonged (24 h) absence of glucose in the culture medium, whereas the cyanide
      caused death which was almost immediate and unspecific to any region cells. In
      contrast, induction of oxidative stress by hydrogen peroxide treatment resulted
      in concentration and time-dependent neuronal death preferentially observed in CA1
      sector of pyramidal layer. Both clinical and experimental studies confirm that
      the hippocampus, and particularly its CA1 sub-field, is exceptionally vulnerable
      to ischaemic and other brain injuries. The causative role of free radical
      generation and the resulting oxidative stress have been widely discussed in these
      pathologies. Our results imply that CA1 pyramidal cells do not differ from the
      other hippocampal neurones in their reaction to metabolic stress. On the
      contrary, and from mainly unknown reasons, these CA1 neurones are extremely
      sensitive to the reactive oxygen-triggered damage.

PMID- 12230255
TI  - Coexistence of diffuse large B-cell lymphoma within pontocerebellar angle
      schwannoma.
AB  - We present an unusual case of diffuse large B-cell lymphoma within
      pontocerebellar angle schwannoma in 62-year-old woman. The patient suffered for 5
      months with V, VII and VIII nerves paresis and with cerebellar ataxia. CT scan
      demonstrated large hyperdensive mass in cerebellopontine angle translocating
      cerebellar hemisphere and cerebral trunk. The patient was subjected to surgery
      and the tumour was removed totally by suboccipital retromastoidal right
      craniectomy approach. Histopathological examination revealed schwannoma
      infiltrated with high grade B-cell lymphoma. The patient did well following
      surgery without any other lymphoma manifestations, and she died from a heart
      attack 20 months later. Solitary lymphoma of pontocerebellar angle coexisting
      with schwannoma is an unusual finding, thus our case is the first report.

PMID- 12230256
TI  - Changes in the volume of temporal lobe structures related to Alzheimer's type
      dementia.
AB  - We compared the volumes of the superior temporal gyrus, basolateral temporal
      area, parahippocampal gyrus, hippocampal head, amygdaloid body and the inferior
      horn of the lateral ventricle in 29 patients with dementia of Alzheimer's type
      (DAT) and in 14 cognitively normal controls. Measurements were performed on
      coronal MR images perpendicular to the long axis of the hippocampus then the raw
      data were normalised for intracranial volume. The volumes of all studied
      structures were significantly smaller in patients with DAT than in age-matched
      control group. The differences in the volume between DAT and age-matched control
      group were the largest for the amygdaloid body and the basolateral temporal area.
      The discriminant analysis including the volume of both the basolateral area and
      the left amygdaloid body allows for correct classification of 100% DAT patients
      and 93% controls. We conclude that the estimation of the volume of the amygdaloid
      body and basolateral temporal area seems to be the most important factor for DAT
      diagnosis.

PMID- 12230257
TI  - An attempt at evaluating borderline conditions of Parkinson's disease and its
      preclinical stage on the basis of clinical and morphological correlation.
AB  - The aim of the investigations was to find to what extent neurodegenerative
      changes develop in the brains of patients with no clinical symptoms of dementia,
      parkinsonism and other neurodegenerative diseases. It has been found that
      neurodegenerative pathology, as evaluated using immunohistochemical methods with
      monoclonal antibodies (Mab) against ubiquitin, tau protein, alpha-synuclein, and
      beta-amyloid, occurs more frequently than the presence of Lewy bodies. The
      degenerative changes involved the neurones of cerebral and cerebellar cortex,
      basal ganglia and medulla oblongata, where neurofibrillary tangles were found.
      Mab positive materials have been found in the cytoplasm of the cell body and the
      cell processes (axons) of the neurones and glial cells. Senile plaques, beta
      amyloid positive, were frequently noted.

PMID- 12230258
TI  - Abnormal nerve conduction velocity as a marker of immaturity in childhood muscle
      spinal atrophy.
AB  - Motor conduction velocity (CV) was tested in 117 infants and children with
      proximal spinal muscular atrophy (SMA), aged 1-53 months, and in 99 age-adjusted
      healthy controls. The children were classified into SMA forms 1 and 2 according
      to SMA International Consortium Criteria. In all children CV was tested in four
      nerves and the following parameters were taken into account: distal latency,
      conduction velocity, amplitude of muscle response. The electromyography of
      muscles revealed neurogenic changes. In all cases of severe form 1 motor CV was
      markedly slowed, with significantly prolonged distal latency and reduced
      amplitude of M response. In surviving children CV, although increasing with age,
      was always below the values of normal age-adjusted children. The slowing was
      particularly pronounced in the femoral nerve. In SMA2 children the values of all
      tested parameters were closer to the values of age-adjusted healthy children,
      nevertheless they were always below the edge of normal values, also the rate of
      maturation was much slower than in normal children. Sensory CV was normal in all
      tested groups. The findings are suggestive of delayed nerve maturation in
      childhood SMA.

PMID- 12230259
TI  - Suspensional reaggregates of human foetal neocortex and tegmentum as objects of
      neurotransplantation.
AB  - Suspensional reaggregates were obtained from human neocortical and tegmental
      anlagen (7 weeks of gestation), using 0.1% tripsin solution, and cultivated in
      Medium 199. Suspensional reaggregates, formed after 2 days in vitro, were grafted
      into the Wistar rat striatum. Incipient stages of histogenesis in the
      reaggregates and their interaction with host brain were investigated using light
      and electron microscopy, with antibodies against vimentin, glial fibrillary
      acidic protein (GFAP), proliferating cell nuclear antigen (PCNA), ferritin, as
      well as lectin ricinus communis agglutinin (RCA). The reaggregates showed a low
      level of tissue organisation. An intermediate condition between suspension and
      the true tissue could be observed in them. These reaggregates had two evident
      features: a rather irregular cell arrangement (without parallel bundles of radial
      glia), and the presence of special intercellular junctions. Some cells made up
      fragments of neuroepithelial sheet in the form of true rosettes. The one-week-old
      grafts were integrated with the host brain as well as dissociated and contained
      host astrocytes. Degenerated cells and detritus appeared rarely. The data of this
      work let us conclude that the suspensional aggregate grafting combines some
      advantages of suspensional and solid grafting methods.

PMID- 12230260
TI  - Ultrastructure of synaptic junctions in the cerebellar cortex in experimental
      valproate encephalopathy and after terminating chronic application of the
      antiepileptic.
AB  - The aim of the study was to analyse in TEM the evolution of changes in structural
      elements of synaptic junctions of the cerebellar cortex in rats in valproate
      encephalopathy induced by chronic 12-month administration of sodium valproate -
      VPA (once daily intragastrically, in a dose of 200 mg/kg b.w.) and after
      withdrawal of this antiepileptic for 1 and 3 months. After 9 and 12 months of the
      experiment, synaptic endings of both the symmetrical and asymmetrical synapses in
      the neuropil of the cerebellar cortex, especially in the molecular layer, showed
      signs of severe damage (mainly swelling) and even disintegration. They were
      mostly observed in axodendritic endings and axospinal endings on the dendritic
      spines of Purkinje cells, being manifested in the presence of large vacuolar
      structures, electron lucent areas and swollen mitochondria within the cytoplasm.
      A reduced number of axonal synaptic vesicles (with more type F vesicles
      preserved) could be seen. One and 3 months after the end of chronic application
      of VPA, the synaptic junctions did not show morphological exponents of the repair
      processes. The alterations observed in the synapticjunctions of the cerebellar
      cortex may suggest disorders in neurotransmission processes, such as exhaustion
      and damage caused by ischaemia due to damage to the blood-brain barrier induced
      by VPA and/or its toxic metabolites.

PMID- 12230261
TI  - Studies on the pharmacokinetics of total and free valproate in mono- and
      bitherapy with carbamazepine in epileptic children and adolescents.
AB  - The aim of this study was to obtain a pharmacokinetic calculation for valproic
      acid (VPA) and its free fraction in 50 children and adolescents (4-18 years)
      treated for epilepsy in VPA monotherapy and bitherapy with carbamazepine (CBZ).
      The diurnal fluctuation of serum concentration of total and free VPA during
      monotherapy was observed. The additional antiepileptic medication of VPA and CBZ
      was connected with prominent diurnal free VPA serum fluctuations. Pharmacokinetic
      parameters of total and free VPA in monotherapy were significantly different. The
      change of free and total VPA pharmacokinetics during bitherapy with CBZ was
      observed, too. No changes in half-life time of VPA in mono- and bitherapy were
      noticed. The variability of pharmacokinetic parameters of free VPA suggests the
      need for monitoring unbound VPA plasma concentrations during bitherapy with CBZ.

PMID- 12230262
TI  - Clinical significance of alpha1-adrenoceptor selectivity in the management of
      benign prostatic hyperplasia.
AB  - Alpha1-adrenoceptor antagonists have been shown to provide effective relief from
      symptoms of benign prostatic hyperplasia (BPH) with attendant improvements in
      quality of life. Although the alpha1A-adrenoceptor subtype predominates over
      other subtypes of alpha1 adrenoceptors in the prostate gland, there is no
      evidence that a subselective alpha-adrenoceptor antagonist provides a clinical
      advantage over a selective alpha1-adrenoceptor antagonist in the treatment of
      patients with BPH. The pharmacokinetic profiles of alpha1A-adrenoceptor
      antagonists and their documented penetration of the blood-brain barrier (CNS
      adverse effects) preclude a clinical benefit of subselective alpha-adrenoceptor
      blockers over selective alpha1 blockers.

PMID- 12230263
TI  - Application of clenbuterol in the treatment of urinary incontinence.
AB  - The treatment of urinary incontinence represents an important medico-social
      problem, notwithstanding the offered 90 products of treatment. The authors
      summarice their experience on the treatment of urinary incontinence with
      clenbuterol for the period 1988-1997. During this period total of 335 patients
      (163 women and 72 men), aged between 30 and 73 were treated. The medicine was
      used in the treatment of women with stress incontinence (60) and urge
      incontinence (103). In cases of combination between urinary incontinence and
      hyperreflexy of the detrusor, and antiholynergic therapy was used. It was used
      after surgery of the adenoma of the prostate in men, aged 62-73: in 50 of them
      after transvesical prostatectomy, and in 22 after transurethral resection of the
      prostate. The authors determine the period of using the product in the different
      kinds of incontinence. Clenbuterol can be effective only when sfincter activity
      is preserved, which is proved by means of urodynamic tests. The durability of
      treatment was stable in 86% of treated women, and in 76.3% of treated men. The
      authors determine the indications and contraindications of administration of
      celbuterol. They analise the changes in the hydrodynamic of the lower urinary
      tract in the patients with urinary incontinence after clenbuterol therapy.

PMID- 12230264
TI  - Effect of parathyroid hormone related protein, and dihydrotestosterone on
      proliferation and ornithine decarboxylase mRNA in human prostate cancer cell
      lines.
AB  - OBJECTIVES: Parathyroid hormone related protein (PTHrP) has been identified as
      the major hormone responsible for the syndrome of humoral hypercalcemia of
      malignancy (HHM). Recent studies have shown that a large number of prostate
      tumors demonstrate the presence of PTHrP despite the fact that prostate cancer is
      rarely associated with the HHM syndrome. Other studies have indicated that PTHrP
      behaves as an early response gene, which stimulates ornithine decarboxylase (ODC)
      enzyme activity, an enzyme, involved in the biosynthesis of polyamines. It is
      therefore possible that PTHrP regulates prostate tumor cell proliferation via ODC
      gene expression. METHODS: In the present study, we evaluated the effects of PTHrP
      and/or dihydrotestosterone (DHT) treatment on DNA synthesis by thymidine
      incorporation in androgen-dependent (LnCaP) and androgen-independent (PC3) human
      prostate adenocarcinoma cell lines. In addition, we utilized Northern blot
      analysis to investigate the effect of PTHrP [1-34] alone or in combination with
      DHT on ODC mRNA. RESULTS: PTHrP [1-34] treatment resulted in an increase in
      thymidine uptake in PC3 cells by 50%, whereas no such increase was seen in LnCaP
      cells. However, in the LnCaP cells, in the presence of DHT, PTHrP stimulated DNA
      synthesis to a level greater than that seen with DHT alone. DHT (10 nM) treatment
      resulted in an induction of PTHrP as well as ODC mRNAs in the androgen-dependent
      (LnCaP) but not in androgen-independent (PC3) cell line. PTHrP [1-34] treatment
      resulted in induction of ODC mRNA in the LnCaP cells. Addition of DHT resulted in
      a further increase in the ODC mRNA expression. CONCLUSIONS: These data suggest
      that PTHrP may play a role in prostate cancer cell proliferation and the
      increased ODC gene expression may be one possible mechanisms responsible for this
      phenomenon.

PMID- 12230265
TI  - Measurements of nuclear size in collecting tubules of the kidney of rats during
      prolonged hypokinesia and ambulatory conditions.
AB  - Hypokinesia (decreased motor activity) induces significant morphological changes
      in the kidneys, but little is known about the effect of hypokinesia (HK) on the
      collecting duct nuclei of the kidney. The aim of this study was to measure the
      effect of prolonged HK on the nuclear size in the inner meduallary collecting
      ducts on the kidney of rats. Studies were done on one hundred ninety-two 13-week
      old male rats (370 to 390 g) during 15 days pre HK period and 90 days HK period.
      Rats were equally divided into two groups: vivarium control rats (VCR) and
      hypokinetic rats (HKR). The HKR group kept in small individual cages. Nuclear
      size in renal collecting tubules, fluid excretion, sodium (Na) and potassium (K)
      in plasma and urine, plasma aldosterone (PA) and antidiuretic hormone (ADH) and
      body weight were measured. A significant (p < or = 0.01) increase in size of the
      collecting duct nuclei of the kidney, PA, plasma and urinary Na and K and fluid
      loss, and a significant (p < or = 0.01) decrease of body weight and plasma ADH
      observed in the HKR group when compared with the VCR. The measured parameters did
      not change significantly in the VCR group when compared with their baseline
      control values. It was concluded that prolonged HK induces a significant increase
      of the nuclear size in the inner meduallary collecting ducts of the kidney of
      hypokinetic rats when compared with the control rats.

PMID- 12230266
TI  - Renal Doppler ultrasonography in infants with hydronephrosis.
AB  - The objective was to evaluate the importance of obstruction in unilateral
      hydronephrosis by using renal Doppler ultrasonography. A total of 19 infants were
      examined. It was revealed that patients of group with obstruction have in the
      affected kidney a higher mean resistive index [RI = 0.77 +/- 0.04] than in the
      healthy kidney [RI = 0.69 +/- 0.02] [p < 0.001]. In patients of group with
      nonobstructive dilatation this difference was not observed. In infants it is not
      possible to evaluate only absolute changes of the resistive index. It is much
      more useful to compare values of RI of both kidneys using the above indices. The
      determination of RI, RIR and delta RI can be helpful in distinguishing obstructed
      from non-obstructed hydronephrosis.

PMID- 12230267
TI  - Interaction of nitric oxide and cell adhesion molecules after 24 hours of
      complete ureteric obstruction in the rats on a solitary kidney.
AB  - We aimed to show whether the administration of exogenous L-Arg would alter the
      morphological, functional changes and interaction of nitric oxide and cell
      adhesion molecules such as tenascin and lectin after release of twenty-four hours
      complete ureteric obstruction in the solitary rat kidney tissue. Forty
      prepubertal Wistar-Albino rats were separated into 4 groups, each containing 10
      rats. In the group 1 (Sham-control, n = 10), right nefrectomy was performed; the
      left ureter was visualized but not ligated. In the remaining 30 rats, the abdomen
      was opened and undergone right nephrectomy and the left ureter was completely
      obstructed. After 24 hours, thirty rats were divided as group 2, 3, and 4, each
      containing 10 rats. In-group 2, no drug treatments were given. In-group 3 L-Arg
      (L-arginine methyl ester) was infused immediately after abolishing ureteric
      obstruction. In-group 4 L-NAME was give separately during L-Arg administration
      during 30 minutes immediately after abolishing ureteric obstruction. Than, the
      animals were prepared for functional and histopathological studies. BUN value was
      decreased significantly in L-Arg group when compared with untreatment and L-NAME
      groups (p < 0.05, p < 0.001 respectively). Creatinine values were decreased in L
      Arg group when compared with untreatment group (p < 0.002). Urine flow and
      urinary Na value was increased significantly in L-Arg group when compared to
      other obstruction groups (p < 0.001, p < 0.001). The increase in the number of
      macrophages in Untreated and L-NAME group were significant (p < 0.001, p < 0.001)
      when compared to L-Arg group. Immunohistochemical study showed that tenascin and
      lectin expression was severe in tubulus basal membrane of untreated and L-NAME
      treated rats. In L-Arg group, tenascin and lectin expression was moderate in
      tubulus membrane. Our results suggest that the administration of exogenous L-Arg
      protect the functional and degenerative effects of acute complete obstruction in
      the solitary kidney tissue of the rats. Nitric oxide cause these positive effects
      by decreasing preglomerular vascular resistance, regulation of neutrophil
      function and preventing the expression of cell adhesion molecules such as
      tenascin and lectin.

PMID- 12230268
TI  - Hyponatremic dehydration: an analysis of 78 cases.
AB  - Our purpose was to determine the frequency of convulsion in children with
      hyponatremic dehydration (HD). We also investigated whether or not there was a
      relationship between the severity of hyponatremia and the degrees of malnutrition
      in our region (Eastern Anatolia of Turkey) in where malnutrition is frequently
      observed. In this study, the clinical and laboratory findings of 78 patients with
      diarrhoea (acute, persistent or chronic diarrhoea) and HD were studied. When
      diarrhoea lasts longer than 2 and 4 weeks they were accepted as persistent and
      chronic diarrhoea, respectively. Patients were said to have HD if they had the
      clinical findings of dehydration associated with hyponatremia [Serum sodium (SNa)
      <130 mmol/L)]. Nutritional status of the children was assessed by the Gomez
      classification using weight for age; it was accepted as normal those were between
      90%-110%, mild malnutrition 75%-89%, moderate malnutrition 60%-74% and severe
      malnutrition <60%. Of 78 patients, 40 were boys, 38 were girls. The age and
      weight of the patients ranged from 40 days to 36 months (8.94 +/- 5.49 months)
      and from 2000 to 10,300 g (5535.25 +/- 1702.10 g) respectively. All patients
      except four had malnutrition; 15 (20.3%) had mild malnutrition, 30 (40.5%) had
      moderate malnutrition and 29 (39.2%) had severe malnutrition. Forty-seven
      patients had acute, 16 patients had persistent, and 15 patients had chronic
      diarrhoea. SNa levels were between 104 and 129 mmol/L (121.21 +/- 6.12 mmol/L).
      There was not statistically a significant difference between SNa level and the
      degree of malnutrition, and SNa level and the types (acute, persistent or
      chronic) of diarrhoea (p > 0.05). Of 78 patients, 12 (15.3%) patients had
      convulsion, of whom eight had convulsion associated with fever. Convulsion was
      noted in nine (19.1%) and three (18.7%) patients with acute and persistent
      diarrhoea, respectively (p > 0.05). Also, we observed that when hyponatremia was
      severer, convulsions tended to be more occuring (p < 0.05). Five (6.4%) children
      died and all of them had severe malnutrition and septicemia. We determined that
      the frequency of convulsion in HD was 15.3% (12/78), and there was not a
      difference between the cases of acute, persistent and chronic diarrhoea for the
      frequency of convulsion. We also found a significant difference was not present
      between SNa level and the degree of malnutrition, and between SNa level and the
      types (acute, persistent or chronic) diarrhoea. However, we observed that when
      hyponatremia was severer, convulsions tended to be more occuring.

PMID- 12230269
TI  - Primitive neuroectodermal tumor of the kidney: a rare entity.
AB  - Primitive neuroectodermal tumor (PNET) is usually aggressive and rapidly
      progressing and metastasizing tumor. Occurrence of the this type of tumor in the
      kidney is considered as unusual, and few cases have been reported so far. We
      present a PNET arising from the kidney in a 23-year-old female patient.

PMID- 12230270
TI  - Spontaneous rupture of hydronephrotic solitary functioning kidney during
      pregnancy.

PMID- 12230272
TI  - Urinary schistosomiasis: urographic features and significance of drooping kidney
      appearance.
AB  - The purpose of the study was to analyse the urographic features of
      schistosomiasis and to see the theurapeutic implications of "drooping kidney"
      appearance for the urologists. Over a period of one year, 1636 patients
      undergoing intravenous urography (IVU) were analysed to look for urographic
      features of schistosomiasis. A total of 136 patients revealed the classical
      urographic feature such as ureteric strictures, vesical and ureteric
      calcification and calculi etc. 131 of these patients were of Egyptian origin. In
      addition to above mentioned classical features, 8 patients (6%) with urinary
      schistosomiasis revealed "drooping kidney" appearance. In the remaining patients
      with no evidence of clinical or urographic features of urinary schistosomiasis,
      only one patient (0.07%) showed similar bilateral appearance. Renogram in 6 to 8
      patients with "drooping kidney" revealed poorer renal function on the affected
      side. Ureteroscopy (URS) revealed more florid ureteritis cystica on the side with
      "drooping kidney" in 6 out of 8 patients compared with the normal side. URS also
      confirmed the presence of a kink and more difficulty with insertion of J stents.
      "Drooping kidney" a new urographic feature of urinary schistosomiasis may have
      theurapeutic implications for the urologists and should be looked for on the
      I.V.U. of patients with urinary schistosomiasis.

PMID- 12230271
TI  - Combined interferon alpha with levamisole in patients with metastatic renal cell
      carcinoma.
AB  - To evaluate the efficacy and toxicity of interferon alpha-2b (IFN-alpha2b) and
      levamisole treatment regimen in patients with metastatic renal cell carcinoma
      (RCC). Seventeen patients with metastatic RCC were treated using recombinant IFN
      alpha2b at a dose of 10 MU/m2 body surface subcutaneously three times in a week,
      for 3 months, with levamisole 50 mg t.d.s orally on days 1-3 on alternate weeks.
      The mean follow-up period was 10.7 (range 2-23) months. We achieved 1 complete
      response (lasting for 12+ months) and 1 partial response (lasting for 15 months),
      for an objective response rate of 11.7%. A further 7 patients (41%) had a
      stabilization of disease. The overall toxicity was moderate, with mainly grade I
      or II side effects. Grade III toxicities reported among 3 patients including
      vomiting (2 patients) and anorexia (1 patient). There was no treatment related
      death. Although additions of levamisole to IFN-alpha do not result in any
      significant increase in treatment toxicity, the response rate appears to be no
      better than IFN-alpha monotherapy reported in the literature.

PMID- 12230273
TI  - Pedunculated prolapsing bladder hematoma (pseudotumor) mimicking an anterior
      vaginal polyp--a clinical curiosity and rare complication of transurethral
      resection of bladder tumor.
AB  - A young woman who presented with a recurrent bladder tumor was detected on follow
      up to be harboring a prolapsed bladder tumor at the external urinary meatus
      mimicking an anterior vaginal polyp. Excision and histopathological examination
      revealed an organized hematoma (pseudotumor). The literature regarding this
      clinical curiosity and its differential diagnosis is reviewed and discussed.

PMID- 12230274
TI  - Prognostic value of cystocopically pseudotumoral lesions (inflammation/granuloma)
      in primary stage T1 grade 3 bladder tumors treated with BCG.
AB  - OBJECTIVE: The aim of this study is to find out whether the pseudotumoral lesions
      (inflammation/granuloma) seen at the follow-up cystoscopy performed three to six
      months after transurethral resection of primary stage T1 grade 3 bladder tumor
      and instillations of BCG therapy might have some prognostic value as far as
      recurrence and/or long term progression are concerned. MATERIAL AND METHODS: From
      the first group of one hundred and thirteen patients with primary stage of T1
      grade 3 bladder tumor treated with 81 mg of BCG Connaught (weekly/during six
      weeks), those with recurrent tumor at the 3rd and 6th month were excluded, so we
      evaluated 99 patients. We identified 13 patients with cystoscopically
      pseudotumoral lesions. RESULTS: of the 13 cystoscopically pseudotumoral lesions,
      we observed recurrence in two cases (15%), while among the rest of the 86
      patients, we observed 22 recurrences (26%) (p = 0.9; not significant). Concerning
      progression, eight cases were reported out of 86 patients (9%) within the
      cistocopically normal group. No cases of progression were reported among the 13
      patients with cystoscopically pseudotumoral lesions. This difference was not
      statistically significant (p = 0.5). CONCLUSIONS: The patients with
      cystoscopically pseudotumoral lesions (inflammation/granuloma) are a reduced
      group (13%) with less tendency to recurrence and without progression, even though
      this relationship is not significant.

PMID- 12230275
TI  - The relation of mutant p53 accumulation in transitional cell carcinoma of bladder
      with pathological stage, grade, recurrence and survival.
AB  - In this study prognostic significance and clinical value of mutant p53 gene in
      bladder transitional cell tumors is investigated. In our clinic, between 1997
      2000, transurethral resection was performed in 48 cases, 3 females (6%) and 45
      males (94%) with the diagnosis of primary bladder tumor, age ranges between 30-81
      years old (average 58.9 +/- 9.9). The patients whose pathology results were
      transitional cell carcinoma were gathered into two groups as p53 positive and p53
      negative by immunohistochemical study. These cases who were followed 1-36 months
      were compared to each other for pathologic state, tumor grade, recurrence and
      survival. It's found out that mutant p53 accumulation is related to high grade
      and pathologic stage tumors. But it's concluded that p53 positivity doesn't
      effect recurrence and survival rates.

PMID- 12230276
TI  - CD44 standard form expression as a predictor of progression in high risk
      superficial bladder tumors.
AB  - OBJECTIVE: The purpose of this study was to assess the significance of the
      standard CD44 adhesion molecule expression in predicting progression of high risk
      superficial bladder carcinoma in the short term. METHODS: Sixty-six patients (51
      males and 15 females, aged 27 to 89 years (mean 64.75 years) with primary
      superficial transitional cell bladder cancer initially treated with transurethral
      resection (TURBT) were enrolled in the study. Only pTa/pT1 grade 2 multiple
      tumors as well as all grade 3 tumors were included in this study. All tumor
      samples obtained after the resection were immunohistochemically evaluated for the
      expression of the CD44 standard molecule. Fifty eight patients remained during
      the follow up period which ranged from 3 to 36 months (mean 11.8 months). Tumor
      progression in the short term was considered as the critical end point of
      interest in this study. The prognostic significance of tumor stage, grade,
      presence of carcinoma-in-situ (CIS) and expression of CD44 in determining the
      risk for progression, was studied with both univariate (log rank test) and
      multivariate (Cox proportional hazards) methods of analysis. RESULTS: Kaplan
      Meier survival curves indicated that a shorter median progression-free survival
      is expected for those patients with G3 bladder tumors (p = 0.0055), concomitant
      CIS (p = 0.0051), and loss of expression of CD44 (p = 0.0015), whereas a similar
      association with stage was not detected (p = 0.5793). The cox regression
      multivariate analysis did not yield a significant result for any of the studied
      parameters therefore no one of the factors taken into account can serve as an
      independent predictor of progression in superficial bladder cancer in the short
      term. CONCLUSION: The immunohistochemically detectable loss of the expression of
      CD44 standard form from superficial bladder tumor samples may be, complementary
      to the established prognostic factors, a useful predictor of tumor progression in
      the short term.

PMID- 12230277
TI  - Intravesical treatment of severe bacillus Calmette-Guerin cystitis.
AB  - OBJECTIVE: Intravesical instillation of bacillus Calmette-Guerin (BCG) is an
      established treatment of carcinoma in situ and recurrent superficial bladder
      tumours. The inflammatory reaction due to BCG provokes cystitis of short duration
      as a frequent side effect. When the symptomatology is severe and long-lasting,
      different systemic treatments have been administered with varying degrees of
      efficacy. MATERIAL AND METHODS: We have studied the treatment of severe BCG
      cystitis with a anaesthetic anti-inflammatory solution administered by
      intravesical instillations to 16 patients. RESULTS: Good results were obtained in
      94% of the cases, with immediate clinical improvement in terms of pain and
      urinary symptoms, and with no side effects. CONCLUSIONS: This treatment is
      inexpensive and easy to administer. We consider that it offers a useful option to
      solve an infrequent but very annoying problem for the patients.

PMID- 12230278
TI  - Carcinoma urinary bladder presenting as acute abdomen.
AB  - Bladder perforation presenting as acute peritonitis is a rare and dramatic event
      in the course of carcinoma urinary bladder. We present one such case and discuss
      the presentation, management and brief follow-up.

PMID- 12230279
TI  - The efficacy of alfuzosin treatment in patients with prostatism.
AB  - OBJECTIVE: Alfuzosin, a quinazoline derivative, is a selective alpha-la
      adreneceptor antagonist with further selectivity for the alpha-1 adrenoceptors of
      the lower urinary tract and lesser affinity for vascular alpha-1 adrenoceptors.
      The present study evaluates the efficacy of alfuzosin in a group of the patients
      with prostatism. METHODS: Eighty-two patients with lower urinary tract symptoms
      aged from 55 to 76 years (mean age 62.36 +/- 6.4) were enrolled in the study. The
      patients were evaluated by blood pressure measurement, digital rectal
      examination, serum total and free prostate specific antigen (PSA) determinations
      by Tandem R-Assay with the reference range of 0.0 to 4.0 ng/ml, international
      prostate symptom score (IPSS), volume measurement by transrectal prostate
      ultrasound, blood biochemistry, uroflowmetry, postvoiding residual urine (PVRU)
      assessment. The patients treated with alfuzosin 2.5 mg three times a day for 3
      months were re-evaluated by blood pressure measurement, IPSS, urine flow rate
      (UFR) and PVRU assessment in the 2nd week and in the 6th week, and by blood
      pressure measurement, IPSS, blood biochemistry, serum total and free PSA
      determinations, UFR and PVRU assessment in the 3rd month. Statistical analysis
      was performed using student-t test, and p value was considered significant when
      less than 0.05. RESULTS: Although IPSS significantly decreased in the 2nd week of
      the treatment compared to pre-treatment value, it reached a maximum decrease in
      the 6th week of the treatment. There were statistically significant difference
      between in the 2nd week IPSS value and the 6th week IPSS value. However, no
      difference was seen between the 6th week IPSS value and the 3rd month IPSS value.
      No significant difference was observed between pre-treatment values and the 2nd
      week values regarding UFR and PVRU. Peak flow rate and PVRU significantly changed
      in the 6th week of the treatment and they reached maximum change in the 3rd
      month. Difference was also significant between the values in the 6th week of the
      treatment and those in the 3rd month of the treatment. According to the blood
      biochemical analysis, total and free PSA levels before and after the treatment,
      there were no significantly difference. Additionally, alfuzosin had no effect on
      blood pressure. Before, during and after the treatment, blood pressure did not
      change significantly. CONCLUSION: Present study showed that symptomatic
      improvement with alfuzosin treatment began in the 2nd week, reaching the maximum
      level in the 6th week whereas urodynamic parameters began to improve in the 6th
      week and reached the maximum level in the 3rd month with no effect on blood
      pressure and blood biochemical test.

PMID- 12230280
TI  - Prostate cancer and coexisting incidental Paget's disease--report on a case.
AB  - Prostate cancer coexisting with asymptomatic Paget's disease (osteitis deformans)
      may be difficult to stage. The skeletal lesions of both prostate cancer and
      Paget's disease may closely resemble each other, as appearing on imaging. A case
      of clinically localized prostate cancer coexisting with incidental Paget's
      disease is herein reported. Prostate cancer and coexisting incidental Paget's
      disease both need careful evaluation and close follow-up of the skeleton by
      imaging, because there is a risk of the former involving the skeleton at low
      clinical stages and low PSA serum levels, as well as the latter developing
      osteosarcoma.

PMID- 12230281
TI  - The relation of prostate biopsy results and ratio of free to total PSA in
      patients with a total PSA between 4-20 ng/mL.
AB  - OBJECTIVE: In this study our aim was to investigate the efficacy of free to total
      PSA ratio in discrimination of benign prostate hyperplasia and prostate cancer.
      MATERIALS AND METHODS: A total of 194 patients, 52 to 82 years old (mean 66.06 +/
      0.47 years) with PSA levels between 4 to 20 ng/mL were included into this study.
      Each patient underwent sextant prostate biopsy under transrectal ultrasound
      guidance. The patients were divided into two groups as PSA 4-10 and 10-20 ng/mL.
      Patients with benign and malign results were compared with respect to age, total
      PSA level, free PSA level and free/total (f/t) PSA ratio. RESULTS: Biopsies
      revealed prostate cancer in 16 of 130 patients (12.3%) with serum PSA 4-10 ng/mL
      and in 10 of 64 patients (15.6%) with serum PSA 10-20 ng/ml. In both PSA groups
      free PSA and f/t PSA levels were statistically significant, where total PSA
      levels were not. In patients with 4-20 ng/mL total PSA levels and a cut off level
      of < 0.18 for f/t PSA, the sensitivity, specificity and positive predictive value
      for prostate cancer were 88.5%, 53.6% and 20.4% respectively. CONCLUSION: Higher
      levels of PSA suggest prostate cancer, but still additional parameters are needed
      for patients with PSA 4-20 ng/mL, such as free PSA and f/t PSA. Although a cut
      off level of < 0.18 for f/t PSA seems to be the most accurate one to discriminate
      benign and malign diseases further studies on larger groups of patients are
      needed.

PMID- 12230282
TI  - Case report--Cutaneous metastasis from a primary transitional cell carcinoma of
      prostate.

PMID- 12230283
TI  - Prostato-cutaneous fistula following injection of internal haemorrhoids with oily
      phenol.

PMID- 12230284
TI  - Case report--Prostatic carcinoma presenting as an epididymal nodule.

PMID- 12230285
TI  - The assessment of constipation in monosymptomatic primary nocturnal enuresis.
AB  - OBJECTIVES: Nocturnal enuresis and constipation are common pediatric problems.
      The aim of this study was to assess the incidence of constipation in children
      with or without monosymptomatic primary nocturnal enuresis. METHODS: The study
      included 5350 children, ages 5-19 years, who were surveyed to detect the
      incidence of nocturnal enuresis. Of those surveyed, 679 (12.7%) had primary
      nocturnal enuresis. All children were questioned by mail with a standard form
      that addressed their micturition and defecation habits. The children those who
      had primary nocturnal enuresis were invited to the Pediatric Urology Section of
      the University Hospital. Of those 679 children, 125 kept that invitation. All 125
      of those children underwent an abdominal ultrasound. Also, these children had
      serum creatinine levels drawn and plain abdominal films taken. RESULTS:
      Constipation, defined as less than 3 bowel movements per week, was seen in 48 of
      679 children with nocturnal enuresis (7.06%). Of those 4671 children without
      nocturnal enuresis, only 68 (1.45%) had constipation. The difference in
      constipation between the two groups was statistically significant (z = -9.251; p
      = 0.000). Of note, 10 of the 125 children (8%), evaluated at the hospital, had
      constipation. None of the children had an abnormal neurologic examination.
      Finally, faecal loading was detected on the plain films of 8 of the 125 children
      evaluated, 7 of who had constipation. The sensitivity of grading plain films for
      faecal loading to denote constipation in this population was 87.5%. CONCLUSIONS:
      Children with primary nocturnal enuresis should be thoroughly assessed for
      coexisting constipation.

PMID- 12230286
TI  - Percutaneous retrograde varicocele embolisation using tungsten embolisation
      coils: a five year audit.
AB  - OBJECTIVE: To assess the efficacy of percutaneous retrograde varicocele
      embolisation using Spirale tungsten coils over a period of five years. PATIENTS
      AND METHODS: Fifty consecutive patients underwent local anaesthetic day case
      varicocele embolisation via a right femoral approach. Venous anatomy was
      identified and classified. Morbidity and recurrence were recorded at three month
      clinical follow up. RESULTS: The procedurewas technically successful in 94% of
      the patients. The varicocele recurred in 16%, the majority of whom had complex
      venous anatomy. 8% of the patients complained of discomfort at follow up.
      CONCLUSIONS: Although the coils used in this study have been withdrawn, a high
      technical success rate is described with failure being predominantly due to
      complex venous anatomy.

PMID- 12230287
TI  - Bilateral testicular germ-cell tumors--a single centre long-term experience.
AB  - OBJECTIVES: The incidence of bilateral testicular tumors (BTT) had increased over
      the preceding decade. The aim of the present study is to analyse a group of
      patients with BTT and to high-light the need for long-term follow-up of patients
      treated in a single centre. MATERIAL AND METHODS: 27 (2.8%) out of 960 patients
      with germ-cell testicular tumors (GCTT), treated between 4/1977 and 8/2001,
      developed bilateral disease. All of them underwent radical orchiectomy (in one
      patient was done delayed orchiectomy after primary chemotherapy due to advanced
      disease). Additional treatment was planned according to the histologic type and
      clinical stage of the disease, and previous treatment as well. The survival data
      were reviewed. RESULTS: 24 out of 27 patients (88.9%) developed the 2nd tumor
      metachronously (median interval 66 months, range, 4-197 months) and three (11.1%)
      had synchronous BTT. Only 7 patients (25.9%) had identical histological types on
      both sides (6 of them with pure seminomas, one with embryonal carcinoma). Two of
      three synchronously developed BTT had different histologic types on both sides.
      GCTT of one histologic type were observed in respect of the first tumor: 11
      seminomas, three embryonal carcinomas, in respect of the 2nd tumor: 10 seminomas,
      three embryonal carcinomas, in respect of the 2nd tumor: 10 seminomas, three
      embryonal carcinomas and one mature teratoma. GCTT of more than one histologic
      type were observed in respect of the first and the 2nd tumors: 6 mixed GCTT with
      seminoma component and 7 without seminoma component. Majority of BTT was
      presented in clinical stage I (in respect of the first tumor in 70.4%, in respect
      of the 2nd tumor in 62.9%). The median duration of the follow-up after the
      diagnosis of the first GCTT was 149 months (range, 13-288 months) and after the
      diagnosis of the contralateral GCTT was 68 months (range, 1-167 months). Twenty
      five patients (92.6%) were alive with NED at their last follow-up visit. Two
      patients died by mean of 22.5 months (range, 21-24 months) after the 2nd
      orchiectomy. CONCLUSIONS: All patients with unilateral GCTT have an increased
      risk of developing a contralateral testicular tumor, even decades after
      diagnosis. Management should be individualised for each patient.

PMID- 12230288
TI  - Metachronous tumors of testis in undescendent and ectopic testis.

PMID- 12230289
TI  - Analyses of 98 seminoma cases: a review article.
AB  - 98 Patients with seminoma were treated at Clinic of Radiation Oncology of Gulhane
      Military Medicine Academy between the years 1974-1995. All cases were undergone
      orchiectomy. The median age of the patients whom were staged respectively 76%,
      17%, 7% according to AJCC system, stage I, stage II and stage III was 28 (20-58).
      While 87 patients were undergone only radiotherapy, 11 patients with advanced
      stage had taken chemotherapy with radiotherapy. In 52 months of median follow up
      duration, 5 year disease free survival rates were 98.6%, 93.3%, 25% and 94.5% for
      stage I, stage II, stage III and all stages respectively. As a result, we can
      propose that the seminoma is a disease with good results in oncology. In our view
      detailed staging and new treatment approaches in advanced disease will achieve
      better results in the future.

PMID- 12230290
TI  - Fournier's gangrene: can aggressive treatment save life?
AB  - Fournier's gangrene (FG) is a rapidly progressive, fulminant infection of the
      scrotum, perineum and the abdominal wall. FG is caused by synergic aerobic and
      anaerobic organisms. Modern surgical series report mortality of up to 67%. This
      originally rare disease has become more frequent. Aggressive treatment including
      antibiotics, antigangrenous serum, and treatment of all accompanied diseases and
      disorders can be successful. Treatment also includes debridement and plastic
      corrections. Authors describe management of 8 patients with FG. Treatment of FG
      and all accompanied diseases was in all cases successful. Treatment costs of this
      kind of patients were approximately 20 times higher than treatment of patients
      with other urologic diseases.

PMID- 12230291
TI  - Conformal radiotherapy in primary non-Hodgkin's lymphoma of the male urethra.
AB  - Primary malignant lymphoma of the urethra is very rare. Fifteen cases are
      reported in the literature and only four of them belong to the male urethra. We
      present the fifth case of primary Non-Hodgkin's lymphoma of the male urethra that
      is managed by conformal radiotherapy.

PMID- 12230292
TI  - Changes of endogenous erythropoietin level and iron status during a 30-month
      hemodialysis treatment of a group of patients.
AB  - In our earlier paper we found that among 50 hemodialysis patients (HD pts) 48%
      (24 pts) control anemia with hemoglobin (Hb) concentration >9.5 g/dl and
      hematocrit (Hct) >30% without recombinant human erythropoietin (rHuEpo) therapy.
      These HD pts had significantly higher mean endogenous erythropoietin (eEpo) level
      and lower iron reserves (IR) than HD pts who need rHuEpo therapy. The aim of this
      study was to judge whether the possibility to control anemia in pts not requiring
      rHuEpo therapy changes during a 30-month HD treatment. Serum eEpo and ferritin
      were measured every 6 months. After 30 months of HD treatment 18 pts remained in
      this group--5 pts died, 1 underwent transplantation. During the study period 4/18
      pts permanently had a very low level of eEpo (under detection limit), 7/18 had
      the level of eEpo within normal range for healthy control, 7/18 pts had a high
      level of eEpo (up to 3 times higher than the mean for healthy control). Pts who
      had the highest level of eEpo had the lowest IR. After 30 months IR were
      significantly lower than at the beginning of observation (292 +/- 87 vs 143 +/-
      127 mg). Important negative correlation between eEpo and IR was observed
      throughout the whole period of study: r = -0.4820, p < 0.02 at the start of the
      study, and r = -0.6126, p < 0.007 after 30 months of treatment. The study shows
      that the possibility to control anemia in pts not treated with rHuEpo did not
      change significantly during 30 months of HD treatment. Endogenous Epo level in HD
      pts not treated with rHuEpo varied between different pts: it was permanently low
      in some pts, permanently high in others and stayed normal in remaining pts.

PMID- 12230293
TI  - Clinical approach to urinary incontinence: a comparison between internists and
      geriatricians.
AB  - To compare the initial approach and pattern of practice between internists and
      geriatricians in treating urinary incontinence. A retrospective chart review of
      300 consecutive charts of elderly patients over the age of 65, seen by either
      internists (IM) or Geriatricians (GERI) for urinary incontinence at the Cleveland
      Clinic Florida was performed. The clinical approaches to the management of
      urinary incontinence were compared between IM and GERI groups by using a
      Student's t test. The mean age for these patients was 77 y for the IM group and
      79 y for the GERI group. Majority of patients suffered from two chronic
      illnesses. We found that geriatricians performed more initial work up such as
      urodynamic testing before referring, while internists obtained more referrals to
      gynecologist with special interest in urologic disorders (currently called
      urogynecologist) without initial workup. IM and GERI groups equally prescribed
      medications for incontinence. However, the GERI group recommended Kegel exercises
      more frequently. This study showed that geriatricians manage urinary incontinence
      more extensively by performing more initial work up including urodynamics and
      providing initial behavioral therapy (Kegel exercise and toilet schedule) before
      referring to specialists. Perhaps geriatricians feel more comfortable treating
      urinary incontinence as shown by their lower frequency of referrals and are
      therefore more comfortable than internists at addressing this medical issue. On
      the contrary, the internist did the initial evaluation but preferred to get a
      referral perhaps due to less familiarity with urinary incontinence.

PMID- 12230294
TI  - Prevalence of mild impairment in renal function in a random sample of elders from
      a biethnic community survey.
AB  - The purpose of this study was to compare the prevalences of renal impairment,
      notably an elevation in serum urea nitrogen and/or serum creatinine
      concentration, in a randomly selected, biethnic population of Hispanic and non
      Hispanic white men and women, and to determine the associations with coronary
      heart disease and its risk factors (diabetes, hypertension, and dyslipidemia). A
      survey of health and health-related issues was conducted on 883 volunteers, mean
      age 74.1 years, randomly selected from the Medicare rolls of Bernalillo County
      (Albuquerque), New Mexico. Equal numbers of Hispanic and non-Hispanic white men
      and women were selected and recruited. A fasting serum creatinine and serum urea
      nitrogen was included in the battery of laboratory tests. Mild elevations of SUN
      and serum creatinine concentrations are common (9.2%) in an aging, randomly
      selected population (mean age 74.1 years). Males were more commonly affected than
      females. There were no differences between Hispanics and non-Hispanic whites,
      even though diabetes was twice as prevalent in Hispanics. Mild elevations of SUN
      and serum creatinine were more common in participants with coronary heart disease
      and its risk factors (diabetes, hypertension, and dyslipidemia). All participants
      with mild renal impairment had either increased total cholesterol or decreased
      HDL-cholesterol. One cannot determine from a cross-sectional study whether the
      dyslipidemia consistently associated with mild renal impairment was a cause of
      the renal impairment or a result of the renal impairment; however, biological
      explanations do exist to explain how the dyslipidemias can lead to progressive
      glomerulosclerosis.

PMID- 12230295
TI  - The effect of vitamin B6 and folate supplements on plasma homocysteine and serum
      lipids levels in patients on regular hemodialysis.
AB  - BACKGROUND: Hyperhomocysteinemia is an independent risk factor for cardiovascular
      events. The aim of this study was to show the results of the reduction of
      homocysteine in end stage renal failure patients on hemodialysis, as it is known,
      have higher levels of homocysteine than other groups of subjects. METHODS: Plasma
      homocysteine concentration was determined before and after the administration of
      vitamin B6 and folic acid in 12 patients (males: 6) on regular dialysis therapy.
      Mean monthly fasting serum concentrations of total cholesterol (TCHOL), HDL-chol,
      LDL-chol and triglycerides (TRG) were determined for a period 68 months (12-120
      months) before and 26 months after the administration of vitamin B6 and folic
      acid. RESULTS: Mean serum concentrations for folic acid and vitamin B12 before
      and after the administration were: folic acid: 5.03 +/- 4.9 and 18.0 +/- 19.2
      ng/mL, (p < 0.0001) and B12: 456 +/- 257 and 514.38 +/- 307 pg/mL respectively).
      Plasma homocysteine was reduced significantly after the administration of above
      drugs (from 47 +/- 14 to 29 +/- 9 micromol/mL, p < 0.001). This reduction of
      homocysteine resulted in a modification of the patients' lipidemic profile: Serum
      LDL-chol was decreased significantly (119 +/- 38 mg/dL to 110 +/- 35 mg/dL,
      p<0.005). TCHOL and TRG were also decreased but not significantly (190 +/- 45
      mg/dL to 187 +/- 43 mg/dL and 116 +/- 63 mg/dL to 108 +/- 47 mg/dL
      respectively)). Serum concentrations HDL-chol were increased significantly (from
      42 +/- 10 mg/dL to 47 +/- 10 mg/dL, p < 0.001). The atherogenic index for
      cholesterol, LDL/HDL, was 1.6 times lower after the drugs receiving (before:
      LDL/HDL = 3.1 and after: LDL/HDL = 2.5, p < 0.001). CONCLUSIONS: These results
      indicate that the folate and vitamin B6 supplementation resulted in reduction of
      homocysteine levels and improvement of lipidemic profile in regular dialysis
      patients.

PMID- 12230296
TI  - Hypertension in the elderly.
AB  - Both systolic and diastolic blood pressure increase with advanced age and more
      than 50% of hypertensive patients are aged above 65 years. Age-related vascular
      and neuro-humoral changes are important factors leading to the development of
      hypertension in the elderly and the increase in systolic and diastolic blood
      pressure with age in any individual is a consequence of the relative change in
      arterial resistance and stiffness. Therefore, hypertension is predominantly or
      purely systolic in the elderly both in women and men. The risks of hypertensive
      patients over the age of 65 years are significant and several trials have
      provided compelling evidence that treatment of hypertension in the elderly is
      beneficial in terms of reduced morbidity and mortality. Goal blood pressure
      should be similar in older and younger patients. Lifestyle modifications are of
      proven benefit and may be the only therapy needed for stage 1 hypertension. The
      Sixth report of the JNC recommends diuretics, specifically thiazide diuretics as
      the initial choice for the treatment of elderly patients without any comorbid
      conditions. Beta-blockers are less effective than thiazides as first line
      treatment and may only reduce stroke events. Recently, dihydropiridine calcium
      antagonists have been advocated as first choice agents for the treatment of
      hypertension in the elderly and are suitable alternatives when diuretics are
      ineffective, contraindicated or not tolerated. Newer drugs such as AT1
      antagonists are also effective in lowering blood pressure in the elderly but
      large scale data concerning their protective effects are still lacking.

PMID- 12230297
TI  - Vascular access for dialysis in the elderly.
AB  - Although not taken in consideration as a special issue in current guidelines,
      vascular access in the elderly deserve specific recommendations as they are
      quickly enlarging as a group, with particularly high vascular access morbidity
      and failure rate. Hemodynamic and endothelial mechanisms of access failure are
      reviewed and tentative strategies to increase the prevalence of durable native
      arteriovenous fistulas are analysed.

PMID- 12230300
TI  - Geriatric nephrology and urology literature.

PMID- 12230299
TI  - Effect of acetylsalicylic acid and dipyridamole in primary membranoproliferative
      glomerulonephritis type I.
AB  - Primary membranoproliferative glomerulonephritis (MPGN) has a poor long-term
      prognosis, with 40 per cent of patients reaching end-stage renal failure after 10
      years of observation. Approximately 35 per cent of patients die due to
      complications of the nephrotic syndrome. This study investigates the effect of
      acetylsalicylic acid (ASA) combined with dipyridamole on proteinuria and renal
      function in nephrotic MPGN patients with normal/moderately reduced glomerular
      filtration rate (GFR). Fourteen patients with biopsy-proven type I MPGN received
      ASA (1000 mg/day) and dipyridamole (300 mg/day) for 24 months. Proteinuria was
      reduced from 6.8 +/- 2.4 g/day to 1.1 +/- 0.6 g/day (p < 0.001). Serum albumin
      levels increased from 2.2 +/- 0.5 g/dL to 3.7 +/- 0.4 g/dL (p < 0.001) during the
      study period after 24 months compared to baseline. Serum creatinine and GFR did
      not significantly change in patients treated with acetylsaliclylic acid and
      dipyridamole during the observation period (p < 0.05). Our study suggests that
      ASA combined with dipyridamole significantly reduces proteinuria without
      impairing renal function in patients with MPGN.

PMID- 12230298
TI  - Dietary electrolytes and hypertension in the elderly.
AB  - The effect of age on older hypertensive patient's blood pressure response to
      increased sodium intake is well known. Salt sensitivity which does increase with
      age and the decrease in renal function limiting the ability of aged kidney to
      excrete sodium load are major factors, responsible for rise in blood pressure
      during Na consumption in the elderly. Clinical studies encourage salt reduction
      with and without weight loss. Although potassium consumption is highly
      recommended, one should be aware of potassium overload in the elderly.

PMID- 12230301
TI  - The solved and unsolved mysteries of the genetics of early-onset Alzheimer's
      disease.
AB  - Approximately half of the Alzheimer's disease (AD) cases that are associated with
      early onset appear to be transmitted as a pure genetic, autosomal dominant trait.
      Genetic analyses of these pedigrees have found three causal genes: betaAPP,
      presenilin 1 (PS1), and presenilin 2 (PS2). This review provides an update on the
      pathological consequences of mutations in early-onset AD genes, the phenotypic
      heterogeneity of those cases, and future directions for research and clinical
      practice.

PMID- 12230304
TI  - DNA base-excision repair enzyme apurinic/apyrimidinic endonuclease/redox factor-1
      is increased and competent in the brain and spinal cord of individuals with
      amyotrophic lateral sclerosis.
AB  - Motor neurons degenerate in amyotrophic lateral sclerosis (ALS). The mechanisms
      for this neuronal cell death are not known, although apoptosis has been
      implicated. Oxidative damage to DNA and activation of p53 has been identified
      directly in motor neurons in cases of ALS. We evaluated whether motor neuron
      degeneration in ALS is associated with changes in the levels and function of the
      multifunctional protein apurinic/apyrimidinic endonuclease (APE/Ref-1). APE/Ref-1
      functions as an enzyme in the DNA base-excision repair pathway and as a redox
      regulation protein for transcription factors. The protein level and localization
      of APE/Ref-1 are changed in ALS. Immunoblotting showed that APE/Ref-1 protein
      levels are increased in selectively vulnerable central nervous system (CNS)
      regions in individuals with ALS compared to age-matched controls. Plasmid DNA
      repair assay demonstrated that APE from individuals with ALS is competent in
      repairing apurinic (AP) sites. DNA repair function in nuclear fractions is
      increased significantly in ALS motor cortex and spinal cord. Immunocytochemistry
      and single-cell densitometry revealed that APE/Ref-1 is expressed at lower levels
      in control motor neurons than in ALS motor neurons, which are decreased in number
      by 42% in motor cortex. APE/Ref-1 is increased in the nucleus of remaining upper
      motor neurons in ALS, which show a 38% loss of nuclear area. APE-Ref-1 is also
      upregulated in astrocytes in spinal cord white matter pathways in familial ALS.
      We conclude that mechanisms for DNA repair are activated in ALS, supporting the
      possibility that DNA damage is an upstream mechanism for motor neuron
      degeneration in this disease.

PMID- 12230303
TI  - Adverse effect of a presenilin-1 mutation in microglia results in enhanced nitric
      oxide and inflammatory cytokine responses to immune challenge in the brain.
AB  - Inflammatory processes involving glial cell activation are associated with
      amyloid plaques and neurofibrillary tangles, the cardinal neuropathological
      lesions in the brains of Alzheimer's disease (AD) patients, However, it is
      unclear whether these inflammatory processes occur as a response to neuronal
      degeneration or might represent more seminal events in the disease process. Some
      cases of AD are caused by mutations in presenilin-1 (PS1), and it has been shown
      that PS1 mutations perturb neuronal calcium homeostasis, promote increased
      production of amyloid beta-peptide (Abeta), and render neurons vulnerable to
      synaptic dysfunction, excitotoxicity, and apoptosis. Although glial cells express
      PS1, it is not known if PS1 mutations alter glial cell functions. We now report
      on studies of glial cells in PS1 mutant knockin mice that demonstrate an adverse
      effect PS1 mutations in microglial cells. Specifically, PS1 mutant mice exhibit
      an enhanced inflammatory cytokine response to immune challenge with bacterial
      lipopolysaccharide (LPS). LPS-induced levels of mRNAs encoding tumor necrosis
      fctor-alpha (TNFalpha), interleukin (IL)-1alpha, IL-1beta, IL-1 receptor
      antagonist, and IL-6 are significantly greater in the hippocampus and cerebral
      cortex of PS1 mutant mice as compared to wild-type mice. In contrast, the
      cytokine responses to LPS in the spleen is unaffected by the PS1 mutation.
      Studies of cultured microglia from PS1 mutant and wild-type mice reveal that PS1
      is expressed in microglia and that the PS1 mutation confers a heightened
      sensitivity to LPS, as indicated by superinduction of inducible nitric oxide
      synthase (NOS) and activation of mitogen-activated protein kinase (MAPK). These
      findings demonstrate an adverse effect of PS1 mutations on microglial cells that
      results in their hyperactivation under pro-inflammatory conditions, which may,
      together with direct effects of mutant PS1 in neurons, contribute to the
      neurodegenerative process in AD. These findings also have important implications
      for development of a "vaccine" for the prevention or treatment of AD.

PMID- 12230305
TI  - The actin-binding domain of spinophilin is necessary and sufficient for targeting
      to dendritic spines.
AB  - Spinophilin is enriched in dendritic spines, small protrusions of the
      postsynaptic membrane along the length of the dendrite that contain the majority
      of excitatory synapses. Spinophilin binds to protein phosphatase 1 with high
      affinity and targets it to dendritic spines, therefore placing it in proximity to
      regulate glutamate receptor activity. Spinophilin also binds to and bundles f
      actin, the main cytoskeletal constituent of dendritic spines, and may therefore
      serve to regulate the structure of the synapse. In this study, we sought to
      determine the structural basis for the targeting of spinophilin to dendritic
      spines. Our results show that the actin-binding domain of spinophilin is
      necessary and sufficient for targeting of spinophilin to dendrites and dendritic
      spines.

PMID- 12230302
TI  - Autism: in search of susceptibility genes.
AB  - Autism is a neurodevelopmental disorder of unknown etiology. There is convincing
      data for the involvement of genetic factors in the development of autism, and the
      absence of any consistent evidence for an environmental, neuroanatomical, or
      biochemical cause has led to an increasing number of genetic studies to determine
      the basis of this complex disorder. The results of recent genetic linkage and
      candidate gene studies are reviewed in relation to the challenge of clinical and
      genetic heterogeneity, and prospects for the future of genetic research in autism
      are considered.

PMID- 12230307
TI  - The mosquito-malaria theory.

PMID- 12230306
TI  - Methamphetamine-induced TNF-alpha gene expression and activation of AP-1 in
      discrete regions of mouse brain: potential role of reactive oxygen intermediates
      and lipid peroxidation.
AB  - Cellular and molecular mechanisms of methamphetamine (METH)-induced neurotoxicity
      may involve alterations of cellular redox status and induction of inflammatory
      genes. To study this hypothesis, molecular signaling pathways of METH-induced
      inflammatory responses via activation of redox-sensitive transcription factors
      were investigated in discrete regions (corpus striatum, frontal cortex, and
      hippocampus) of mouse brain. Intraperitoneal injection of METH at a dose of 10
      mg/kg body weight resulted in a significant increase in oxidative stress, as
      measured by 2,7-dichlorofluorescein (DCF) fluorescence assay, thiobarbituric acid
      reactive substances (TBARS), and total glutathione levels. Glutathione peroxidase
      activity was also significantly increased after METH exposure. In addition, DNA
      binding activity of activator protein-1 (AP-1), a redox-responsive transcription
      factor, was increased in all studied brain regions in response to METH treatment.
      Because AP-1 is known to regulate expression of inflammatory genes, levels of TNF
      alpha mRNA were also studied. Expression of the tumor necrosis factor-alpha (TNF
      alpha) gene was induced 3 h after METH injection and remained elevated for up to
      6 h of METH exposure. In addition, stimulation of the TNF-alpha gene was
      associated with increased TNF-a protein production in the frontal cortex. These
      results suggest that METH-induced disturbances in cellular redox status and that
      activation of AP-1 can play a critical role in signaling pathways leading to
      upregulation of inflammatory genes in vivo. Furthermore, these data provide
      evidence for the role of oxidative stress in the neurotoxic effects of METH.

PMID- 12230308
TI  - The role of the mosquito in the evolution of the malarial parasite: the recent
      researches of Surgeon-Major Ronald Ross, I.M.S. 1898.

PMID- 12230309
TI  - Experimental proof of the mosquito-malaria theory. 1900.

PMID- 12230310
TI  - Multiple sclerosis: can Schwann cells wrap it up?

PMID- 12230311
TI  - Reference values for erythrocyte sedimentation rate of middlescent people as a
      function of altitude.
AB  - The purpose of this paper is to provide a scientific basic for a unified standard
      for the reference value of middlescent people's erythrocyte sedimentation rate
      (ESR) in China. ESR measurements for healthy middlescent people were collected
      according to the Wintrobe method and the relationship between the reference value
      of middlescent people's ESR and altitude was tested in this paper It was found
      that the reference value of middlescent people's ESR decreases when the altitude
      gradually increases, and the relationship is quite significant. Univariate
      regression analysis was used to deduce two regression equations: Y1 = 13.14
      0.00245X +/- 2.98 (males) and: Y2 = 22.00-0.00397X +/- 4.85 (females). If the
      altitude value of a particular area of China is known, the reference value of
      middlescent people's ESR can be calculated by means of these regression
      equations. Furthermore, depending on the altitude, China can be divided into
      three biogeographic districts: Qingzang District, Central District, and Eastern
      District.

PMID- 12230312
TI  - Use of urinary gram stain for detection of urinary tract infection in childhood.
AB  - In this study, urinary culture, urinary Gram stain, and four tests within the
      urinalysis, leukocyte esterase, nitrite, microscopyfor bacteria, and
      microscopyforpyuria, were examined in 100 children with symptoms suggesting
      urinary tract infection. Our purpose was to determine the validity of the urinary
      Gram stain compared with a combination of pyuria plus Gram stain and overall
      urinalysis (positiveness of nitrite, leukocyte esterase, microscopy for bacteria,
      or microscopy for white blood cell). Of 100 children, aged two days to 15 years,
      70 (70 percent) had a positive urinary culture: 40 girls (57 percent) and 30 boys
      (43 percent). Escherichia coli was the most common isolated agent. The
      sensitivity and specificity of the urinary Gram stain were 80 percent and 83
      percent, and that of the combination of pyuria plus Gram stain 42 percent and 90
      percent, and that of the overall urinalysis 74 percent and 3.5 percent
      respectively. Our findings revealed that neither method of urine screen should
      substitute for a urine culture in the symptomatic patients in childhood.

PMID- 12230314
TI  - Exosomes: novel organelles implicated in immunomodulation and apoptosis.

PMID- 12230313
TI  - Quality-of-life measurements: origin and pathogenesis.
AB  - Despite extensive growth in recent years, the field of "quality-of-life"
      appraisal still evokes debate about basic perception of the concept and is
      accompanied by a plethora of indexes for measurement. One prime reason for the
      problems is that the measurements have been transferred from two separate sources
      - medical health status indexes and social-science population indexes - neither
      of which was designed for appraising the particular personal distinctions of the
      way people feel about their own quality of life. When regulatory and commercial
      incentives were offered for measuring patients' quality of life, it became
      appraised with the indexes available from the medical and psychosocial sources,
      even though neither set of indexes was specifically intended for that purpose.
      They are not developed from the basic principle that a person's "quality of life"
      is a state of mind, not a state of health, which is uniquely perceived by that
      person, and which will not be appropriately appraised unless the most cogent
      personal components are allowed suitable expressions. An approach that lets
      patients state their own opinions directly can offer the "face validity" or
      "common sense" that now seems absent from the generally applied measurements.

PMID- 12230315
TI  - Medical management of obesity.
AB  - Obesity is the most prevalent and serious nutritional disease among western
      countries and is rapidly replacing undernutrition as the most common form of
      malnutrition in the world. Approximately 300,000 deaths a year are currently
      associated with overweight and obesity, second only to cigarette smoking as a
      leading cause of preventable death in the United States. Obesity effects 9 organ
      systems and is a risk factor for gastroesophageal reflux disease, nonalcoholic
      fatty liver disease, cholelithiasis, and colon cancer. Evidence-based guidelines
      on the identification, evaluation, and treatment of overweight and obesity have
      recently been developed by the National Institutes of Health to help
      practitioners effectively manage their patients. The body mass index is used to
      classify weight status and risk of disease. Treatment for obesity includes
      lifestyle management, consisting of diet therapy, physical activity, and
      behavioral modification, and may include pharmacotherapy or surgery based on
      level of risk. Currently only 2 medications, sibutramine and orlistat, are
      approved for long-term use. An initial weight loss of 10% of body weight achieved
      over 6 months is a recommended target. This article reviews the evaluation and
      management of the adult obese patient.

PMID- 12230316
TI  - Surgical management of obesity.
AB  - Bariatric surgery has undergone significant change in the past several decades.
      There are now several attractive surgical options for the management of
      clinically severe obesity (body mass index > 40 kg/m2). Gastric restrictive
      procedures predominate and have been performed with acceptable complication
      rates. Long-term weight loss is frequently > 50% excess weight with amelioration
      of obesity-related illnesses. Laparoscopic approaches are increasingly popular.
      Patient selection and appropriate follow-up remain challenging aspects of patient
      care. In summary, bariatric surgery is a reliable option for the surgical
      management of clinically severe obese patients.

PMID- 12230317
TI  - Nutritional chemoprevention of colon cancer.
AB  - Evidence emerging from many different types of experimental designs continues to
      support the concept that dietary habits, and nutritional status, play important
      roles in determining the risk of developing colorectal cancer. Overall, a diet
      habitually high in fresh fruits and vegetables, modest in calories and alcohol,
      and low in red meat and animal fat is cancer protective. This field of
      investigation is nevertheless very confusing, particularly because longstanding
      hypotheses, such as the presumed protective effects of fruits, vegetables, and
      fiber, have recently been challenged by well-designed prospective trials. The
      search for individual components in the diet that convey protection continues:
      calcium, folate, and selenium are the leading candidates in this regard. There is
      also growing interest in other plant-based compounds, so-called phytochemicals,
      although our understanding of their effects is quite rudimentary at present.
      However, regardless of the constituent components of the diet, evidence continues
      to accrue that ingesting a sensible amount of calories and maintaining a
      desirable weight also play important roles in prevention of this cancer. Although
      the inconsistencies in this field make it tempting to minimize its import, there
      is little question that diet has a major impact on colorectal cancer risk;
      diligent attention to the rigorous conduct of studies and their interpretation
      will likely clarify these relationships over the next decade, much to the benefit
      of public health.

PMID- 12230318
TI  - Issues of nutritional support for the patient with acute pancreatitis.
AB  - Management strategies in the nutritional support of the patient with acute
      pancreatitis have changed dramatically over the past 10 years. Prospective
      randomized trials show that maintaining gut integrity is equally as important as
      placing the pancreas at rest while inflammation within the gland resolves. In
      comparison to total parenteral nutrition and gut disuse, enteral feeding
      attenuates disease severity, reduces oxidative stress, and improves patient
      outcome. Nasojejunal feeds infused at or below the Ligament of Treitz should be
      provided to those patients with severe pancreatitis, as identified by a number of
      standardized scoring systems such as Ranson Criteria, APACHE II, Glasgow, and
      Imrie scores. Total parenteral nutrition should be reserved only for the patient
      with severe pancreatitis, initiated 4 to 5 days after peak inflammation in whom
      intolerance to enteral feeding has been shown and/or enteral access cannot be
      obtained. Vigilant monitoring is required to assure safe and effective delivery
      of enteral nutrients.

PMID- 12230319
TI  - Nutritional management of short bowel syndrome.
AB  - Short-bowel syndrome refers to malabsorption, diarrhea, and weight loss following
      an extensive resection of small bowel. A main consequence is malabsorption of
      macro- and micronutrients. Nutritional outcome after intestinal resection depends
      on the extent and location of resection, presence of ileocecal valve and a colon,
      functional status of the residual intestine, and adaptation. Intraluminal
      nutrients and trophic factors are critical for intestinal adaptation. The dietary
      management is focused on the enhancement of intestinal adaptation and optimal
      caloric intake. Patients with short-bowel syndrome require an individualized
      diet, and some may require total parenteral nutrition indefinitely. Growth
      hormone, glutamine, and GLP-2 are reviewed with emphasis on their current use in
      clinical practice. The nutritional aspect of short-bowel syndrome is complex,
      with the ultimate goal of weaning the patients from parenteral nutrition.
      Intestinal transplant is a treatment option for select patients.

PMID- 12230320
TI  - Nutritional management of acute and chronic liver disease.
AB  - Malnutrition is a common problem in patients with acute and chronic liver
      disease, and it is near universal in patients undergoing liver transplantation.
      The cause of malnutrition in liver disease is multifactorial. This article
      reviews the prevalence of malnutrition, its pathophysiology, modalities of
      assessing nutritional status, and general guidelines for nutritional support in
      this patient population.

PMID- 12230321
TI  - Pelizaeus-Merzbacher disease.
AB  - Pelizaeus-Merzbacher disease (PMD) can now be defined as an X-linked recessive
      leukodystrophy that is caused by a mutation in the proteolipid protein (PLP) gene
      on chromosome Xq22. The most common mutation is gene duplication followed in
      frequency by missense mutations, insertions, and deletions. The clinical spectrum
      ranges from severe neonatal cases to relatively benign adult forms and X-linked
      recessive spastic paraplegia type 2. The lack of PLP is accompanied by deficits
      in the other myelin proteins of the central nervous system, including myelin
      basic protein, myelin-associated glycoprotein, and cyclic nucleotide
      phosphodiesterase. Surprisingly, the total absence of PLP due to gene deletion or
      a null allele causes a relatively benign form of PMD. Abnormal PLP is thought to
      impair protein trafficking and to induce apoptosis in oligodendroglia.
      Immunocytochemistry with specific antibodies reveals the PLP deficiency and
      insufficient generation of myelin sheaths with the remaining proteins. Both
      excessive biosynthesis of PLP, as in gene duplications, or conformational change
      of the protein, as in missense mutations, are detrimental to myelination. Several
      naturally occurring and transgenic animal models with PLP gene mutations or
      deletions have contributed to our understanding of dysmyelination in PMD and the
      general knowledge of myelination and myelin repair.

PMID- 12230322
TI  - Astrocytes are less efficient in the removal of apoptotic lymphocytes than
      microglia cells: implications for the role of glial cells in the inflamed central
      nervous system.
AB  - Apoptosis of T lymphocytes is a common pathway to terminate autoimmune
      inflammation in the brain as shown in experimental autoimmune encephalomyelitis
      (EAE) and in the autoimmune inflamed human brain. To date it is unclear to what
      extent different glial cells are involved in the removal of apoptotic cells. In
      an in vitro phagocytosis assay we compared the phagocytic capacity of rat
      microglia cells to remove apoptotic lymphocytes with that of astrocytes.
      Apoptosis was induced in autologous thymocytes and myelin basic protein (MBP)
      specific T-cells by methylprednisolone (MP) or by irradiation. Apoptotic cells
      were then added to glial cells that were untreated or prestimulated with
      interferon-gamma (IFN-gamma), interleukin-4 (IL-4), transforming growth factor
      beta (TGF-beta), or tumor necrosis factor-a (TNF-a). Supernatants were collected
      from cell cultures to measure their cytokine secretion. Surface antigen
      expression was analyzed by flow cytometry. Both cell types significantly
      increased their phagocytic activity in response to the addition of apoptotic
      lymphocytes when compared to non-apoptotic cells (p < 0.0001). Astrocytes removed
      only up to one third of the number of apoptotic lymphocytes ingested by microglia
      cells (p < 0.0001). Microglia cells significantly increased their phagocytosis
      rate after IFN-gamma stimulation and decreased it in response to IL-4. In
      contrast, astrocyte phagocytosis was almost unresponsive to cytokine stimulation.
      After interaction with apoptotic cells, microglia secreted significantly less TNF
      alpha. Astrocytic TNF-alpha production was also decreased but not to a
      statistically significant extent. MHC-class II expression after phagocytosis was
      increased on microglia cells but not on astrocytes. Both microglia cells and
      astrocytes are capable of ingesting apoptotic cells, but microglia cells are much
      more efficient phagocytes. Their phagocytic capacity is modulated by the local
      microenvironment and microglial immune function is downregulated after
      phagocytosis. We suggest that in vivo astrocytes might be activated as phagocytes
      once the limit of microglial phagocytic capacity has been reached.

PMID- 12230323
TI  - Human secreted attractin disrupts neurite formation in differentiating cortical
      neural cells in vitro.
AB  - Mutations at the Atrn locus that encodes a transmembrane protein with a large
      ectodomain are responsible for a juvenile-onset neurodegeneration manifest as
      hypomyelination and cerebral vacuole development in several rodent species. In
      addition to a membrane isoform, the human Atm locus generates by alternative
      splicing a secreted form corresponding to the entire ectodomain that then
      circulates at high concentration in the periphery, released in part by activated
      T lymphocytes. We report here that the secreted form mRNA is downregulated
      throughout representative discrete regions of the human brain while membrane
      attractin mRNA is well represented, resulting in the apparent absence of secreted
      attractin protein in cerebrospinal fluid (CSF). Transcription of attractin
      secreted form mRNA is strongly downregulated upon differentiation of a human
      cortical neuron-derived cell line (HCN-1A) to a mature neuron phenotype in
      response to nerve growth factor. Recombinant secreted attractin disrupts neurite
      formation by differentiated HCN-1A cells, resulting in higher levels of branching
      with shorter processes. This effect is duplicated by anti-attractin and by human
      serum but not by human serum depleted of attractin or by CSF We propose that
      inappropriate expression of secreted attractin in the CNS blocks membrane
      attractin function and that its presence, either by leakage from the periphery,
      aberrant transcription, or release from inflammatory foci may affect neuron
      extracellular interactions leading to neurodegeneration in the human.

PMID- 12230324
TI  - Differential expression of vascular endothelial growth factor-A (VEGF-A) and VEGF
      B after brain injury.
AB  - Our previous study demonstrated that vascular endothelial growth factor (VEGF),
      now referred to as VEGF-A, plays a significant role in blood-brain barrier (BBB)
      breakdown and angiogenesis after brain injury. In this study, VEGF-A expression
      was compared with that of VEGF-B in the rat cortical cold injury model over a
      period of 6 hours to 6 days post-injury. VEGF-A and VEGF-B mRNA were detected by
      in situ hybridization and their protein was detected by immunohistochemistry. The
      presence of VEGF-A and VEGF-B proteins in endothelium of lesion vessels was
      related to BBB breakdown by double labeling for either of these growth factors
      and fibronectin, which was used as a marker of BBB breakdown. Significant
      induction of both VEGF-A and VEGF-B mRNA occurred at the lesion site during the
      period of maximal endothelial proliferation. VEGF-A mRNA levels peaked at 3 and 4
      days post-injury and returned to basal expression by day 6, while VEGF-B mRNA
      levels remained elevated up to day 6. VEGF-B protein was constitutively expressed
      in endothelium of all cerebral vessels. After brain injury, there was increased
      immunoreactivity for VEGF-B at the lesion site, this protein being present in the
      endothelium and vascular smooth muscle cells of pial vessels, in inflammatory
      cells, and later in proliferating endothelial cells, endothelium of neovessels,
      and astrocytes. Lesion vessels showing BBB breakdown to fibronectin showed
      endothelial VEGF-A protein but not VEGF-B protein. Constitutive expression of
      VEGF-B in normal endothelium suggests that it may have a role in maintenance of
      the BBB in steady states, while its induction at both the gene and protein level
      post-injury indicates that it has an essential role in angiogenesis and the
      repair processes after brain injury.

PMID- 12230325
TI  - Severe involvement of ambient gyrus in dementia with grains.
AB  - Argyrophilic grains are detected as punctate or filiform structures in the
      neuropil of the medial temporal lobe, and dementia with grains (DG) is defined as
      a form of dementia with argyrophilic grains as the only explainable cause. We
      found argyrophilic grains in 43.2% of our 190 serial autopsy brains (mean age,
      79.7 yr) from a community-based geriatric hospital, but only 20% of these
      argyrophilic grain-positive brains fulfilled the criteria for DG. To determine if
      there are structural differences between cognitively normal cases with
      argyrophilic grains (CNG) and DG, we studied 14 brains with CNG and 15 brains
      with DG. All cases of DG had severe atrophy of the ambient gyrus (the junction
      between temporal lobe and amygdala) with spongiosis, neuronal loss, and gliosis,
      as well as many grains, pretangles, coiled bodies, and tau-immunoreactive
      astrocytes. Comparable changes were not present in the ambient gyrus of CNG
      brains. The temporal neocortex and hippocampus were relatively spared in DG, in
      contrast to Alzheimer disease. Our study suggests that selective severe
      involvement of the ambient gyrus may explain the clinical manifestations of a
      limbic-type dementia in DG.

PMID- 12230326
TI  - Imaging Abeta plaques in living transgenic mice with multiphoton microscopy and
      methoxy-X04, a systemically administered Congo red derivative.
AB  - The identification of amyloid deposits in living Alzheimer disease (AD) patients
      is important for both early diagnosis and for monitoring the efficacy of newly
      developed anti-amyloid therapies. Methoxy-X04 is a derivative of Congo red and
      Chrysamine-G that contains no acid groups and is therefore smaller and much more
      lipophilic than Congo red or Chrysamine-G. Methoxy-X04 retains in vitro binding
      affinity for amyloid beta (Abeta) fibrils (Ki = 26.8 nM) very similar to that of
      Chrysamine-G (Ki = 25.3 nM). Methoxy-X04 is fluorescent and stains plaques,
      tangles, and cerebrovascular amyloid in postmortem sections of AD brain with good
      specificity. Using multiphoton microscopy to obtain high-resolution (1 microm)
      fluorescent images from the brains of living PSI/APP mice, individual plaques
      could be distinguished within 30 to 60 min after a single i.v. injection of 5 to
      10 mg/kg methoxy-X04. A single i.p. injection of 10 mg/kg methoxy-X04 also
      produced high contrast images of plaques and cerebrovascular amyloid in PSI/APP
      mouse brain. Complementary quantitative studies using tracer doses of carbon- 11
      labeled methoxy-X04 show that it enters rat brain in amounts that suggest it is a
      viable candidate as a positron emission tomography (PET) amyloid-imaging agent
      for in vivo human studies.

PMID- 12230327
TI  - Genetic aberrations in gliomatosis cerebri support monoclonal tumorigenesis.
AB  - Gliomatosis cerebri is a rare condition in which the brain is infiltrated by an
      exceptionally diffusely growing glial cell population involving at least 2 lobes,
      though often more extensive, sometimes even affecting infratentorial regions. The
      neoplastic proliferation may have a monoclonal origin, or alternatively, reflect
      progressive neoplastic change of an entire tissue field ("field cancerization").
      The presence of an identical set of genetic aberrations throughout the lesion
      would point to monoclonality of the proliferation. In contrast, the finding of
      non-identical genetic changes in widely separated regions within the neoplasm
      would support the concept of field cancerization. In the present study, a unique
      autopsy case of gliomatosis was available to verify either one of these
      hypotheses. Tissue samples were randomly taken from 24 locations throughout the
      brain and used for genetic investigation. In all samples the histology showed an
      identical picture of slightly elongated astrocytic cells, typical for
      gliomatosis. TP53 exon 5-8 mutation analysis was performed on all samples. Genome
      wide screening for chromosomal aberrations was accomplished by comparative
      genomic hybridization (CGH). In addition, loss of heterozygosity analysis for
      polymorphic markers on chromosomal regions of the 2 most frequently observed DNA
      deletions was carried out. The most widespread genetic aberration was mutation of
      exon 7 of TP53, which was detected in 20 of 24 samples. Bidirectional sequencing
      revealed a mutation in codon 234 (TAC234TGC), resulting in an amino acid
      substitution Tyr-Cys. CGH analysis revealed losses on 2q11-q31 in 13 of 24
      samples and losses on 19q13-qter in 10 of 24 samples from both left and right
      hemispheres. Allelic imbalances for markers on 2q (2q14.3 and 2q22.1) and 19q
      (both 19q13.2) were demonstrated in 10 of 24 and 18 of 24 samples, respectively.
      Other widespread chromosomal aberrations included losses on 3q13-qter and 16q22
      qter and gains on 7q22-qter. The wide distribution of a particular set of genetic
      aberrations in this case supports the concept of monoclonal tumor proliferation.
      The results point to involvement of TP53 mutation in the tumorigenesis of
      gliomatosis cerebri.

PMID- 12230329
TI  - Characteristics of the vertical ground reaction force component prior to gait
      transition.
AB  - The purpose of the study was to examine the vertical ground reaction force
      component when approaching the gait transition point from either a walk-to-run or
      run-to-walk perspective. The vertical ground reaction forces (VGRF) of five steps
      before gait transitions for both walk-to-run and run-to-walk were collected on a
      motor driven treadmill with embedded force plates. Transition specific
      characteristics of the VGRF were observed for both types of gait transition.
      Running peak force and time to peak force reduced dramatically in a quadratic
      fashion as approaching to the run-to-walk transition. The walking VGRF first peak
      increased linearly, and the second peak decreased quadratically prior to walk-to
      run transition. Walking VGRF appearing to be more sensitive to acceleration than
      the running VGRF.

PMID- 12230330
TI  - Childhood movement skills: predictors of physical activity in Anglo American and
      Mexican American adolescents?
AB  - We assessed the relationship between young children's movement skills and their
      physical activity in early adolescence. Balance, agility, eye-hand coordination,
      and skinfold thicknesses in 207 Mexican American and Anglo American children (104
      boys, 103 girls) were measured at ages 4, 5, and 6 years. Habitual physical
      activity was assessed at the age of 12 years by two interviewer-administered 7
      day recalls. Ethnic differences in movement skills were not found. Young girls
      were better at jumping and balancing, and young boys were better at catching.
      Tracking of skills was low, and children's early childhood skills were not
      related to their physical activity 6 years later. Further studies involving
      additional movement skills and other populations are recommended to determine if
      enhanced movement skills in children promote subsequent physical activity.

PMID- 12230328
TI  - BetaAPP and furin mRNA concentrates in immature senile plaques in the brain of
      Alzheimer patients.
AB  - This study examined the possibility that in Alzheimer disease (AD) beta-amyloid
      precursor protein (betaAPP) mRNA is delivered to senile plaques (SPs) via
      dendritic processes. BetaAPP mRNA was detected in SPs by in situ hybridization,
      using a 1.4-kb cRNA in which both [35S]-UTP and [35S]-CTP were incorporated
      together. The betaAPP mRNA was compared with that of furin, a proteolytic enzyme
      putatively involved in betaAPP processing, and its orthologue proprotein
      convertase PCI served as a control. Human presenile AD cases with mostly immature
      SPs and AD cases generally with mature SPs were analyzed. To decrypt SPs after
      hybridization, brain sections were stained with thioflavin S. To establish
      relationships between the density of dystrophic fibers, the degree of plaque
      maturation, and the concentration of mRNA in SPs, the plaque maturity markers
      Abeta(1-42) and Abeta(1-40) peptides were co-localized with neurofilament protein
      200 and compared with microtubule-associated protein 2 (MAP 2). The results
      suggest that immature, Abeta(1-42)- and dystrophic dendrite-containing SPs (but
      not mature SPs containing Abeta(1-40) and missing dystrophic dendrites) are
      capable of concentrating specific mRNAs. Dystrophic dendrites may thus serve as a
      route for the transport of specific mRNAs from the cell bodies to SPs.

PMID- 12230331
TI  - Individual pathways in the development of forceful throwing.
AB  - Halverson, Roberton, and Langendorfer (1982) reported the development of children
      ages 6-13 years filmed longitudinally performing the forceful overarm throw.
      These authors described the children's progress through developmental sequences
      for trunk, humerus, and forearm actions; however, they did not study
      developmental relationships ("profiles") across these components. This paper
      reports how the profiles changed in the same children across trials within
      filming sessions and over time. The data revealed both common and individual
      developmental pathways. The frequencies of some pathways were not chance
      occurrences (p < or = .01), suggesting that within-person constraints eliminated
      certain movement relationships while encouraging others. The authors hypothesize
      that the kinematics of trunk rotation may serve as a control parameter for
      pattern change.

PMID- 12230332
TI  - Cross-cultural validity of the physical self-description questionnaire:
      comparison of factor structures in Australia, Spain, and Turkey.
AB  - We evaluated the cross-cultural generalizability of the factor structure for the
      Physical Self-Description Questionnaire (PSDQ) using confirmatory factor
      analysis. The factor structure was reasonably invariant over large samples of
      responses by Australian, Spanish, and Turkish students. Consistent with a priori
      predictions, the factor structures based on Australian and Spanish high school
      students were somewhat more similar to each other than to those based on Turkish
      university students, but these differences were small. Psychometric, theoretical
      cross-cultural, and practical considerations support the PSDQ's usefulness in a
      variety of research and applied settings. The study also provides a model for
      comparing psychometric properties based on responses to original and translated
      versions of sport psychology measures.

PMID- 12230333
TI  - Postcontraction influences on reaction time.
AB  - The purpose of this study was to compare reaction time (RT) and fractionated RT
      components (premotor and motor times) between normal and postcontraction
      conditions. Twelve participants performed 20 trials each of control and
      postcontraction RT conditions. For the control condition, participants executed a
      learned, rapid, knee-extension contraction response to an auditory stimulus. The
      postcontraction condition was identical to the control condition except that the
      participants performed a 3-s isometric contraction of the knee extensor muscles
      prior to an auditory stimulus. Muscle activity was recorded from the quadriceps
      muscle group. Results indicated that the postcontraction condition was
      significantly faster than the control condition for the average RT, premotor
      time, and motor time. It was concluded that reaction time, processing time, and
      muscle contraction time for a learned task could be significantly reduced
      following an isometric contraction.

PMID- 12230334
TI  - Are intensified physical education sessions able to elicit heart rate at a
      sufficient level to promote aerobic fitness in adolescents?
AB  - The purpose of this study was to determine the effects of intensified physical
      education sessions on adolescents ages 11-16 years. They were divided into two
      experimental groups--high-intensity running group (HIRG) and high-intensity
      jumping group (HlJG)--and a control group (C). During the sessions, heart rate
      (HR) was monitored. There was no significant difference between mean HR for HIRG
      and HIJG, while the mean HR was significantly lower for C (p < .001). For both
      HIRG and HIJG, the mean HR was significantly higher for girls than for boys (p <
      .001). Our results suggested that these intensified physical education lessons
      require a high percentage of maximal HR in adolescents and can be used to improve
      aerobic fitness.

PMID- 12230335
TI  - Effects of multicycle-run training on triathlete performance.
AB  - The purpose of this study was to determine the effect of triathlon training using
      multiple, short cycle-run sequences (multicycle-run training) on cycle-run
      performance. Twelve competitive triathletes, randomized into two groups,
      underwent multicycle-run training or normal training for 6 weeks. During this
      period, baseline training remained the same for both groups, and only the high
      intensity component differed. The differentiated exercises were performed at or
      above 100% maximal aerobic velocity. The improvements in overall cycle-run
      performance were similar (3.3 +/- 1.4 % and 6.1 +/- 1.7% rise in Performance in
      multicycle-run and normal training, respectively). However, the improvement in
      performance was significantly greater for the multicycle-run training (-11.2 +/-
      6.8 s versus -1.2 +/- 7. 7 s for multicycle-run training and normal training,
      respectively) during both the cycle-run change and the first 333-m lap, which
      together are termed the cycle-run transition. We concluded that 6 weeks of
      multicycle-run training did not induce greater improvement in cycle-run
      performance than did normal training in competitive triathletes. However, it did
      induce significant improvement in the cycle-run transition. This finding
      indicates that multicycle-run training may help competitive triathletes to
      develop greater skill and better physiological adaptations during this critical
      transition period of the triathlon race.

PMID- 12230336
TI  - Field testing of physiological responses associated with Nordic Walking.
AB  - This study compared the physiological responses (oxygen consumption and energy
      expenditure) of Nordic Walking to regular walking under field-testing conditions.
      Eleven women (M age = 27.1 years, SD = 6.4) and 11 men (M age = 33.8 years, SD =
      9.0) walked 1,600 m with and without walking poles on a level, 200-m track. For
      women, Nordic Walking resulted in increased oxygen consumption (M = 14.9 ml x kg(
      1) x min(-1), SD = 3.2 vs. M = 1 7.9 ml x kg(-1) min(-1), SD = 3.5; p < .001),
      caloric expenditure (M = 4.6 kcal x min(-1), SD = 1.2 vs. M = 5.4 kcal x min(-1),
      SD = 1.2; p < .001), and heart rate (M = 113.7 bpm, SD = 12.0 vs. M = 118.7 bpm,
      SD = 14.8; p < .05) compared to regular walking. For men, Nordic Walking resulted
      in increased oxygen consumption (M = 12.8 ml x kg(-1) min(-1), SD = 1.8 vs. M =
      15.5, SD =3.4 ml x kg(-1) min(-1); p < .01), caloric expenditure (M = 5.7 kcal x
      min(-1), SD = 1.3 vs. M = 6.9 kcal x min(-1), SD = 1.8; p < .001), and heart rate
      (M = 101.6 bpm, SD = 12.0 bpm vs. M = 109.8 bpm, SD = 14.7; p < .01) compared to
      regular walking. Nordic Walking, examined in the field, results in a significant
      increase in oxygen use and caloric expenditure compared to regular walking,
      without significantly increasing perceived exertion.

PMID- 12230337
TI  - Affective responses to an aerobic dance class: the impact of perceived
      performance.
AB  - The current study tests the mastery hypothesis as an explanation for the
      affective benefits of acute exercise. Participants were 204 undergraduate women
      who were participating in self-selected aerobic dance classes. Following the
      class, participants were asked to rate their exercise performance on a 5-point,
      Likert-type scale. Affect questionnaires were completed prior to and at 5 and 20
      min following the aerobic dance class. Results indicated an overall improvement
      in affect following exercise. Negative valenced subscales were unaffected by
      performance ratings. Both groups showed similar reductions in these states. There
      was, however, a significant Group x Time interaction for the positive valenced
      subscales. High-performance participants reported greater increase in these
      variables throughout recovery than did low-performance participants. These data
      support the mastery hypothesis as an explanation for the exercise-induced change
      in positive affective states.

PMID- 12230338
TI  - Injury rehabilitation: a goal-setting intervention study.
AB  - The study examined the effects of a 5-week goal-setting intervention on athletes'
      rehabilitation adherence, self-efficacy, treatment efficacy, and the
      psychological response variables: dispirited and reorganization. Participants
      were matched across six variables and randomly assigned to one of three groups:
      goal-setting intervention, social support control, and control. The results
      confirmed some of the hypothesized effects of the goal-setting intervention: (a)
      athlete self-report of adherence showed the goal-setting group adhered
      significantly more to the rehabilitation program than the other two groups; (b)
      the goal-setting intervention resulted in significant group differences for self
      efficacy (the goal-setting group having the highest level of self-efficacy); and
      (c) there was a significant increase across time for reorganization and decrease
      across time for dispirited (between specific time phases).

PMID- 12230339
TI  - Injury rehabilitation: a qualitative follow-up study.
AB  - The current qualitative follow-up study was conducted to enhance the
      interpretability and meaningfulness of the findings emerging from a 5-week goal
      setting intervention study with injured athletes. Semistructured interviews were
      conducted with a sample of 9 injured athletes, 3 from each of the three
      intervention study groups (goal-setting, social support control, and control),
      and cross-case summaries were inductively derived. The study highlighted the
      importance of individual difference variables, and the interaction of person and
      situational variables, including support from coaches and club, inability to
      train, weight gain, slowness of progress, physiotherapist support, and the
      importance of long-term outcome goals. Possible mechanisms for the observed
      effects of the goal-setting intervention included the effects of goal-setting on
      self-efficacy, attributions, perceptions of control, and attention.

PMID- 12230340
TI  - The epidemiology of U.S. adults who regularly engage in resistance training.

PMID- 12230341
TI  - Cognitive orientation, precompetition, and actual competition anxiety in
      collegiate softball players.

PMID- 12230342
TI  - Effects of two different strength training modes on motor performance in
      children.

PMID- 12230343
TI  - Comparison of blood lactate levels between swimming in clothes and a swimsuit.

PMID- 12230344
TI  - Contribution of structured exercise class participation and informal walking for
      exercise to daily physical activity in community-dwelling older adults.

PMID- 12230345
TI  - Understanding of athletes' nutritional needs among athletes, coaches, and
      athletic trainers.

PMID- 12230346
TI  - Physical fitness and cardiac risk factors of professional firefighters across the
      career span.

PMID- 12230347
TI  - Response timing accuracy of long-distance movements.

PMID- 12230348
TI  - The timing of specialist evaluation in chronic kidney disease and mortality.
AB  - BACKGROUND: Care for chronic renal failure involves management of complications
      and preparation for possible dialysis. Patients often are not evaluated by
      nephrologists in a timely manner. OBJECTIVE: To identify factors associated with
      late evaluation by a nephrologist and to assess whether late evaluation is
      associated with worse survival once patients develop end-stage renal disease
      (ESRD). DESIGN: National prospective cohort study. SETTING: 81 dialysis
      facilities throughout the United States. PATIENTS: 828 patients with new-onset
      ESRD. MEASUREMENTS: Time from first evaluation by a nephrologist to initiation of
      dialysis, classified as late (<4 months), intermediate (4 to 12 months), or early
      (>12 months); rate of death, from initiation of dialysis to an average of 2.2
      years of follow-up; and demographic, clinical, and laboratory characteristics.
      RESULTS: After adjustment for potential confounders, late evaluation was more
      common among black men than white men (44.8% vs. 24.5%; P < 0.05), uninsured
      patients than insured patients (56.7% vs. 29.0%; P < 0.05) and patients with
      severe comorbid disease than those with mild comorbid disease (35.0% vs. 23.0%; P
      < 0.05). Compared with patients who had early evaluation, the risk for death was
      greater among patients evaluated late and was graded (hazard ratio, 1.3 [95% CI,
      0.87 to 2.06] for patients with intermediate evaluation and 1.8 [CI, 1.21 to
      2.61] for those with late evaluation) after adjustment for dialysis method,
      demographic characteristics, and socioeconomic status in Cox proportional hazards
      regression analysis. After additional adjustment for such factors as the presence
      and severity of comorbid conditions, the association remained graded (hazard
      ratio, 1.2 [CI, 0.73 to 1.82] for patients evaluated at an intermediate point and
      1.6 [CI, 1.04 to 2.39] for those evaluated late). CONCLUSIONS: Late evaluation of
      patients with chronic renal failure by a nephrologist is associated with greater
      burden and severity of comorbid disease, black ethnicity, lack of health
      insurance, and shorter duration of survival.

PMID- 12230349
TI  - Sex differences in cardiac catheterization after acute myocardial infarction: the
      role of procedure appropriateness.
AB  - BACKGROUND: Many studies have found that women are less likely than men to have
      cardiac catheterization after an acute myocardial infarction; however, it is
      unknown whether sex differences reflect inappropriate treatment. OBJECTIVE: To
      ascertain whether cardiac catheterization use after acute myocardial infarction
      in men and women varied by sex and the appropriateness of the procedure, as
      determined by clinical guidelines. DESIGN: Retrospective analysis of chart
      abstracted data. SETTING: U.S. acute-care hospitals. PATIENTS: 143 444 Medicare
      patients who were hospitalized for acute myocardial infarction between 1994 and
      1996. MEASUREMENTS: Cardiac catheterization use within 60 days of hospitalization
      for acute myocardial infarction. RESULTS: Women had lower crude rates of cardiac
      catheterization than men (35.7% for women vs. 46.5% for men [ P < 0.001];
      difference, 10.8 percentage points). Multivariable adjustment for demographic,
      clinical, and hospital characteristics reduced most of the sex differences in
      procedure use (risk-standardized rates, 40.3% for women vs. 41.9% for men [ P <
      0.001]; difference, 1.6 percentage points). Sex differences in cardiac
      catheterization use varied by the appropriateness of the procedure. Risk
      standardized rates of cardiac catheterization were similar for men and women with
      strong indications for the procedure (44.1% for women vs. 44.6% for men [ P >
      0.2]; difference, 0.5 percentage point). Rates of cardiac catheterization use
      among patients with weak indications did not significantly differ between men and
      women (16.5% for women vs. 18.0% for men [ P = 0.096]; difference, 1.5 percentage
      points). Sex differences in cardiac catheterization use were largest for patients
      with equivocal indications (39.4% for women vs. 42.5% for men [ P < 0.001];
      difference, 3.1 percentage points). CONCLUSIONS: Among elderly persons, women
      have lower rates of cardiac catheterization use after an acute myocardial
      infarction than men. However, this difference was attenuated after multivariable
      adjustment, and it occurred primarily in patients with equivocal indications. We
      found no sex variations in procedure use among patients who had strong
      indications for cardiac catheterization.

PMID- 12230350
TI  - Smoking status and risk for recurrent coronary events after myocardial
      infarction.
AB  - BACKGROUND: Questions remain about the importance of smoking and smoking
      cessation after incident myocardial infarction. OBJECTIVE: To assess the
      association between smoking status and risk for recurrent coronary events.
      DESIGN: Retrospective, population-based, inception cohort study. SETTING: Health
      maintenance organization from 1986 to 1996. PATIENTS: 2619 persons who survived
      to hospital discharge after a first myocardial infarction. MEASUREMENTS: Relative
      risk (RR), assessed by using Cox proportional hazards regression analysis, for
      recurrent coronary events in nonsmokers (persons with no history of smoking),
      former smokers (persons who had stopped smoking before infarction), quitters
      (persons who stopped smoking after infarction), and active smokers (persons who
      continued smoking after infarction). RESULTS: At the time of incident infarction,
      33.6% of patients were nonsmokers, 35.5% were former smokers, and 30.9% were
      active smokers. Of the 808 persons who were active smokers at the time of
      incident infarction, 449 quit smoking during hospitalization or after discharge.
      With nonsmokers as the reference group, the multivariable RR for recurrent
      coronary events (n = 433) was 1.17 (95% CI, 0.93 to 1.43) for former smokers and
      1.51 (CI, 1.10 to 2.07) for active smokers. Among quitters, the RR decreased as
      duration of cessation increased: With nonsmokers as the reference group, the RR
      for quitters was 1.62 (CI, 1.02 to 2.61) if the duration of cessation was 0 to
      less than 6 months, 1.60 (CI, 0.97 to 2.60) if the duration was 6 to less than 18
      months, 1.48 (CI, 0.76 to 2.51) if the duration was 18 to less than 36 months,
      and 1.02 (CI, 0.54 to 1.86) if the duration was 36 months or more (P = 0.01 for
      trend). CONCLUSION: After incident myocardial infarction, smoking was associated
      with an elevated risk for recurrent coronary events. In persons who quit smoking
      after infarction, the risk declined to equal that of nonsmokers by 3 years after
      cessation.

PMID- 12230351
TI  - Torsade de pointes associated with very-high-dose methadone.
AB  - BACKGROUND: Methadone is an effective treatment for opioid dependency and chronic
      pain. A methadone derivative, levacetylmethadol, was withdrawn from the European
      market after being associated with torsade de pointes. To date, no association
      between methadone and this arrhythmia has been described. OBJECTIVE: To evaluate
      a series of methadone-treated patients experiencing torsade de pointes. DESIGN:
      Retrospective case series. SETTING: Methadone maintenance treatment programs in
      the United States and a pain management center in Canada. PATIENTS: 17 methadone
      treated patients who developed torsade de pointes. MEASUREMENTS: Chart review for
      concomitant arrhythmia risk factors and quantification of corrected QT interval
      (QTc). RESULTS: The mean daily methadone dose was 397 +/- 283 mg, and the mean
      QTc interval was 615 +/- 77 msec. Fourteen patients had a predisposing risk
      factor for arrhythmia. A cardiac defibrillator or pacemaker was placed in 14
      patients; all 17 patients survived. CONCLUSIONS: This series raises concern that
      very-high-dose methadone may be associated with torsade de pointes. Given the
      likely expansion of methadone treatment into primary care, further investigation
      of these findings is warranted.

PMID- 12230352
TI  - The In-Training Examination in Internal Medicine: an analysis of resident
      performance over time.
AB  - BACKGROUND: The In-Training Examination in Internal Medicine (IM-ITE) has been
      offered annually to all trainees in U.S. medical residency programs since 1988.
      Its purpose is to provide residents and program directors with an objective
      assessment of each resident's personal performance on a written, multiple-choice
      examination and the performance of the residency program compared with that of
      its peers. OBJECTIVE: To analyze trends in the demographic characteristics and
      scores of examinees during the first 12 years of administration of this
      examination. DESIGN: Descriptive analysis over time. SETTING: U.S. residency
      programs in internal medicine, 1988-2000. PARTICIPANTS: Residents at all levels
      of training in categorical, primary care, and medicine-pediatrics programs in the
      United States and Canada. The number of examinees increased from 7500 in 1988 to
      almost 18 000 in 2000. MEASUREMENTS: After calibration of the scores for each
      examination, test results were compared and analyzed for selected cohorts of
      residents over 12 years. RESULTS: More than 80% of residents in medicine training
      programs participate in the IM-ITE, most on an annual basis throughout their
      period of training. Test performance improves at a predictable rate with each
      year of training. Since 1995, international medical school graduates have
      persistently outperformed graduates of U.S. medical schools. Test results were
      affected by the timing of the examination, the time that was available to
      complete the examination, and the actual time that residents spent in internal
      medicine training before each examination. CONCLUSIONS: The IM-ITE scores
      generally improve with year of training time spent in internal medicine training
      before the examination and time permitted to complete the examination. These
      observations provide evidence that the IM-ITE is a valid measure of knowledge
      acquired during internal medicine training.

PMID- 12230353
TI  - Is volume related to outcome in health care? A systematic review and methodologic
      critique of the literature.
AB  - PURPOSE: To systematically review the methodologic rigor of the research on
      volume and outcomes and to summarize the magnitude and significance of the
      association between them. DATA SOURCES: The authors searched MEDLINE from January
      1980 to December 2000 for English-language, population-based studies examining
      the independent relationship between hospital or physician volume and clinical
      outcomes. Bibliographies were reviewed to identify other articles of interest,
      and experts were contacted about missing or unpublished studies. STUDY SELECTION:
      Of 272 studies reviewed, 135 met inclusion criteria and covered 27 procedures and
      clinical conditions. DATA EXTRACTION: Two investigators independently reviewed
      each article, using a standard form to abstract information on key study
      characteristics and results. DATA SYNTHESIS: The methodologic rigor of the
      primary studies varied. Few studies used clinical data for risk adjustment or
      examined effects of hospital and physician volume simultaneously. Overall, 71% of
      all studies of hospital volume and 69% of studies of physician volume reported
      statistically significant associations between higher volume and better outcomes.
      The strongest associations were found for AIDS treatment and for surgery on
      pancreatic cancer, esophageal cancer, abdominal aortic aneurysms, and pediatric
      cardiac problems (a median of 3.3 to 13 excess deaths per 100 cases were
      attributed to low volume). Although statistically significant, the volume-outcome
      relationship for coronary artery bypass surgery, coronary angioplasty, carotid
      endarterectomy, other cancer surgery, and orthopedic procedures was of much
      smaller magnitude. Hospital volume-outcome studies that performed risk adjustment
      by using clinical data were less likely to report significant associations than
      were studies that adjusted for risk by using administrative data. CONCLUSIONS:
      High volume is associated with better outcomes across a wide range of procedures
      and conditions, but the magnitude of the association varies greatly. The clinical
      and policy significance of these findings is complicated by the methodologic
      shortcomings of many studies. Differences in case mix and processes of care
      between high- and low-volume providers may explain part of the observed
      relationship between volume and outcome.

PMID- 12230354
TI  - The choice: Lewellys F. Barker and the full-time plan.
AB  - In 1914, Lewellys F. Barker, William Osler's successor as Professor of Medicine
      and physician-in-chief at Johns Hopkins University School of Medicine, resigned
      to enter private practice rather than accept the terms of a full-time plan,
      whereby professors in clinical departments would be salaried like other
      professors in the university. Barker had been an early proponent of the full-time
      plan. His decision reflected not only a personal desire for a larger income but
      also contradictions inherent in the Flexnerian ideal of clinical medicine as a
      research-oriented university discipline devoid of financial incentives to see
      patients. In private practice, Barker maintained a high profile as a teacher,
      writer, supporter of the Johns Hopkins medical institutions, and public figure.
      The issues raised by his difficult decision remain relevant and have not been
      satisfactorily resolved.

PMID- 12230356
TI  - Screening for postmenopausal osteoporosis: a review of the evidence for the U.S.
      Preventive Services Task Force.
AB  - BACKGROUND: Although osteoporotic fractures present an enormous health burden, it
      is not clear whether screening to identify high-risk persons is appropriate.
      PURPOSE: To examine evidence on the benefits and harms of screening
      postmenopausal women for osteoporosis. DATA SOURCES: MEDLINE (1966 to May 2001),
      HealthSTAR (1975 to May 2001), and Cochrane databases; reference lists; and
      experts. STUDY SELECTION: English-language abstracts that included original data
      about postmenopausal women and osteoporosis and addressed the effectiveness of
      risk factor assessment, bone density tests, or treatment were included. DATA
      EXTRACTION: Selected information about patient population, interventions,
      clinical end points, and study design were extracted, and a set of criteria was
      applied to evaluate study quality. DATA SYNTHESIS: No trials of the effectiveness
      of screening have been published. Instruments developed to assess clinical risk
      factors for low bone density or fractures have moderate to high sensitivity and
      low specificity. Among different bone density tests measured at various sites,
      bone density measured at the femoral neck by dual-energy x-ray absorptiometry is
      the best predictor of hip fracture. Women with low bone density have
      approximately a 40% to 50% reduction in fracture risk when treated with
      bisphosphonates. CONCLUSIONS: Population screening would be based on evidence
      that the risk for osteoporosis and fractures increases with age, that the short
      term risk for fracture can be estimated by bone density tests and risk factors,
      and that fracture risk can be reduced with treatment. The role of risk factor
      assessment and different bone density techniques, frequency of screening, and
      identification of subgroups for which screening is most effective remain unclear.

PMID- 12230355
TI  - Screening for osteoporosis in postmenopausal women: recommendations and
      rationale.

PMID- 12230357
TI  - Specialist evaluation in chronic kidney disease: too little, too late.

PMID- 12230358
TI  - A lesson in poverty.

PMID- 12230360
TI  - Long-term outcome in lupus nephritis.

PMID- 12230362
TI  - Alternative medicine: a mirror image for scientific medicine.

PMID- 12230364
TI  - Quality indicators for management and prevention of falls.

PMID- 12230365
TI  - Clinical inertia.

PMID- 12230366
TI  - Clinical inertia.

PMID- 12230367
TI  - Clinical inertia.

PMID- 12230369
TI  - Guidelines for the management of patients with chronic stable angina.

PMID- 12230370
TI  - High-dose cyclophosphamide for treatment of aplastic anemia.

PMID- 12230372
TI  - Postoperative pulmonary complications.

PMID- 12230375
TI  - Permanent paralysis of the right phrenic nerve.

PMID- 12230376
TI  - Diagnosis by death.

PMID- 12230378
TI  - Central pontine myelinolysis.

PMID- 12230380
TI  - Summaries for patients. Do women with heart attacks get fewer heart procedures
      than men?

PMID- 12230379
TI  - Summaries for patients. Timing of evaluation by specialists for patients with
      chronic kidney disease.

PMID- 12230381
TI  - Summaries for patients. Continued cigarette smoking and the risk for a second
      heart attack.

PMID- 12230382
TI  - Summaries for patients. Very high doses of methadone may cause abnormal heart
      rhythm.

PMID- 12230383
TI  - Summaries for patients. Does quantity mean quality in medical procedures?

PMID- 12230384
TI  - Summaries for patients. Screening for osteoporosis: recommendations from the U.S.
      Preventive Services Task Force.

PMID- 12230385
TI  - Silver(III) carbaporphyrins: the first organometallic complexes of true
      carbaporphyrins.
AB  - Reaction of carbaporphyrins 1 with silver(I) acetate in methanol-CH(2)Cl(2) gave
      excellent yields of the related silver(III) complexes 6. These nonpolar
      organometallic compounds retain fully aromatic properties as judged by UV-vis and
      NMR spectroscopy and were further characterized by X-ray crystallography and
      cyclic voltammetry.

PMID- 12230386
TI  - A novel carboxylate-free ferromagnetic trinuclear mu(3)-oxo-manganese(III)
      complex with distorted pentagonal-bipyramidal metal centers.
AB  - In methanol, the reaction of Mn(ClO(4))(2).6H(2)O and 1,2
      bis(biacetylmonoximeimino)ethane (H(2)bamen) in the presence of triethylamine
      affords a trinuclear complex having the formula [Mn(3)(mu(3)-O)(mu(3)
      bamen)(3)]ClO(4).2H(2)O. The structure of this complex shows a symmetric planar
      central [Mn(III)(3)(mu(3)-O)] unit coordinated to three hexadentate bridging (via
      oximate groups) ligands. The N(4)O(3) coordination sphere around each metal
      center is very close to pentagonal-bipyramidal. A cyclic voltammogram of the
      complex displays two reversible and an irreversible response due to Mn(III)(3) -
      > Mn(III)(2)Mn(IV), Mn(III)(2)Mn(IV) --> Mn(III)Mn(IV)(2), and Mn(III)Mn(IV)(2) -
      > Mn(IV)(3) oxidation processes, respectively. Cryomagnetic data reveal that the
      complex is ferromagnetic.

PMID- 12230387
TI  - Pseudo-polyrotaxane and beta-sheet layer-based three-dimensional coordination
      polymers constructed with silver salts and flexible pyridyl-type ligands.
AB  - A fascinating 3D pseudo-polyrotaxane architecture with 1D polymeric [Ag(bpp)](n)
      chains penetrating 2D (6,3) [Ag(2)(bpp)(2)(ox)](n) sheets and a 3D coordination
      network constructed with 2D infinite [Ag(ppa)](n) beta-sheetlike layers pillared
      by ox ligands (bpp = 1,3-bis(4-pyridyl)propane; ppa = N-(4-pyridinylmethyl)-4
      pyridinecarboxamide; ox = oxalate) have been prepared by utilizing flexible
      pyridyl-type ligands and have been crystallographically characterized. Crystal
      data for 1: monoclinic, space group C2/c, a = 7.619(2) A, b = 19.781(4) A, c =
      26.799(5) A, beta = 94.720(10) degrees, U = 4025.2(15) A(3), and Z = 4. Crystal
      data for 2: monoclinic, space group C2/c, a = 28.947(8) A, b = 8.617(3) A, c =
      16.307(6) A, beta =121.07(1) degrees, U = 3484(2) A(3), and Z = 4.

PMID- 12230388
TI  - Transformation of ammonium dicyanamide into dicyandiamide in the solid.
AB  - Ammonium dicyanamide NH(4)[N(CN)(2)] was synthesized through aqueous ion
      exchange. The crystal structure was investigated by single-crystal X-ray
      diffraction (P2(1)/c, a = 378.67(6) pm, b = 1240.9(3) pm, c = 911.84(14) pm, beta
      = 91.488(18) degrees, Z = 4). It derives from the CsCl structure type. Medium
      strong hydrogen bonds between NH(4)(+) and [N(CN)(2)](-) ions are indicative of
      the observed formation of dicyandiamide H(4)C(2)N(4) during heating. According to
      DSC and temperature-dependent X-ray powder diffractometry, this isomerization is
      exothermic and occurs between 102 and 106 degrees C in the solid. The reaction
      represents the isolobal analogue to the classical synthesis of urea by heating
      NH(4)OCN. While other alkali and alkaline earth dicyanamides undergo
      trimerization or polymerization of their anions during heating, ammonium
      dicyanamide thus shows a different reactivity.

PMID- 12230389
TI  - From linear inorganic chains to helices: chirality in the
      M(pyz)(H(2)O)(2)MoO(2)F(4) (M = Zn, Cd) compounds.
AB  - Cd(C(4)H(4)N(2))(H(2)O)(2)MoO(2)F(4) (C(4)H(4)N(2) = pyrazine, pyz) was
      synthesized via hydro(solvato)thermal methods and characterized by single-crystal
      X-ray diffraction methods (P3(2)()21, no. 154, Z = 3, a = 7.4328(7) A, c =
      16.376(2) A). Both of the known M(pyz)(H(2)O)(2)MoO(2)F(4) (M = Zn, Cd) compounds
      are comprised of trans-M(pyz)(2)(OH(2))(2)F(2) and cis-MoO(2)F(4) octahedra that
      share fluoride vertices to form helical chains along the 3-fold screw axes.
      Individual chains are bridged to six symmetry-equivalent helices through metal
      pyrazine and OH(2)...F and OH(2)...O hydrogen bonds. Structural comparisons of
      similar oxyfluoride chains demonstrate that they can be varied from linear to
      helical through (1) the replacement of pyridine or pyrazine by H(2)O molecules
      and (2) the substitution of cis-directing MoO(2)F(4)(2-) anions in place of trans
      directing WO(2)F(4)(2-) or TiF(6)(2-) anions. Infrared absorption (IR)
      measurements for M = Cd show two distinct O-H stretches corresponding to hydrogen
      bonded O-H...F and O-H...O groups. Contrastingly for M = Zn, IR measurements
      exhibit O-H stretches for averaged hydrogen-bonded O-H...(O/F) groups, free
      (unbound) O-H groups, and higher energy Mo-F stretches. The IR data suggest a
      small fraction of the O-H...F hydrogen bonds are broken in the M = Zn analogue as
      a result of the racemic twinning. Both compounds exhibit nonlinear optical
      behavior, with second harmonic generation (SHG) intensities, relative to SiO(2),
      of approximately 0.25 (<d(ijk)(2epsilon)> = 0.28 pm/V) for the racemically
      twinned Zn(pyz)(H(2)O)(2)MoO(2)F(4) and approximately 1.0 (<d(ijk)(2epsilon)> =
      0.55 pm/V) for the enantiopure Cd(pyz)(H(2)O)(2)MoO(2)F(4).

PMID- 12230390
TI  - Cobalt(II) and cobalt(III) dipicolinate complexes: solid state, solution, and in
      vivo insulin-like properties.
AB  - The synthesis and characterization of Co(II) and Co(III) 2,6
      pyridinedicarboxylate (dipic(2-)) complexes are reported. Solid-state X-ray
      characterizations were performed on [Co(H(2)dipic)(dipic)].3H(2)O and
      [Co(dipic)(mu-dipic)Co(H(2)O)(5)].2H(2)O. Two coordination modes not previously
      observed in dipicolinate transition metal complexes were observed in these
      complexes; one involves metal coordination to the short C-O (C=O) bond, and the
      other involves metal coordination to a protonated oxygen atom. Solution studies,
      including paramagnetic NMR and UV-vis spectroscopy, were done showing the high
      stability and low lability of the Co(III) complex, whereas the Co(II) complexes
      exhibited ligand exchange in the presence of excess ligand. The [Co(dipic)(2)](2
      ) complex has pH dependent lability and in this regard is most similar to the
      [VO(2)dipic](-) complex. The [Co(dipic)(2)](2-) was found to be effective in
      reducing the hyperlipidemia of diabetes using oral administration in drinking
      water in rats with STZ-induced diabetes. Oral administration of VOSO(4) was used
      as a positive control for metal efficacy against diabetes. In addition to
      providing a framework to evaluate structure-function relationships of various
      transition metal complexes in alleviating the symptoms of diabetes, this work
      describes novel aspects of structural and solution cobalt chemistry.

PMID- 12230391
TI  - Modeling substrate- and inhibitor-bound forms of liver alcohol dehydrogenase:
      chemistry of mononuclear nitrogen/sulfur-ligated zinc alcohol, formamide, and
      sulfoxide complexes.
AB  - Using a mixed nitrogen/sulfur ligand possessing a single internal hydrogen bond
      donor (N,N-bis-2-(methylthio)ethyl-N-(6-amino-2-pyridylmethyl)amine (bmapa)), we
      prepared and structurally and spectroscopically characterized a series of zinc
      complexes possessing a single alcohol ([(bmapa)Zn(MeOH)](ClO(4))(2) (1)),
      formamide ([(bmapa)Zn(DMF)](ClO(4))(2) (3), [(bmapa)Zn(NMF)](ClO(4))(2) (4)), or
      sulfoxide ([(bmapa)Zn(DMSO)](ClO(4))(2) (7), [(bmapa)Zn(TMSO)](ClO(4))(2) (8))
      ligand. X-ray crystallographic characterization was obtained for 1.MeOH, 3, 4,
      7.DMSO, and 8. To enable studies of the influence of the single hydrogen bond
      donor amino group of the bmapa ligand on the chemistry of zinc/neutral oxygen
      donor binding interactions, analogous alcohol ([(bmpa)Zn(MeOH)](ClO(4))(2) (2)),
      formamide ([(bmpa)Zn(DMF)](ClO(4))(2) (5), [(bmpa)Zn(NMF)](ClO(4))(2) (6)), and
      sulfoxide ([(bmpa)Zn(DMSO)](ClO(4))(2) (9), [(bmpa)Zn(TMSO)](ClO(4))(2) (10))
      complexes of the bmpa (N,N-bis-2-(methylthio)ethyl-N-(2-pyridylmethyl)amine)
      ligand system were generated and characterized. Of these, 2, 5, 6, and 9.2DMSO
      were characterized by X-ray crystallography. Solution spectroscopic methods ((1)H
      and (13)C NMR, FTIR) were utilized to examine the formamide binding properties of
      3-6 in CH(3)CN and CH(3)NO(2) solutions. Conclusions derived from this work
      include the following: (1) the increased donicity of formamide and sulfoxide
      donors (versus alcohols) makes these competitive ligands for a cationic N/S
      ligated zinc center, even in alcohol solution, (2) the inclusion of a single
      internal hydrogen bond donor, characterized by a heteroatom distance of
      approximately 2.80-2.95 A, produces subtle structural perturbations in N/S
      ligated zinc alcohol, formamide, or sulfoxide complexes, (3) the heteroatom
      distance of a secondary hydrogen-bonding interaction involving the oxygen atom of
      a zinc-coordinated alcohol, formamide, and sulfoxide ligand is reduced with
      increasing donicity of the exogenous ligand, and (4) formamide displacement on a
      N/S-ligated zinc center is rapid, regardless of the presence of an internal
      hydrogen bond donor. These results provide initial insight into the chemical
      factors governing the binding of a neutral oxygen donor to a N/S-ligated zinc
      center.

PMID- 12230392
TI  - Lewis acidity of gallium halides.
AB  - The Lewis acidity of GaF(3), GaF(2)Cl, GaFCl(2), and GaCl(3) in acid-base
      interactions has been studied by taking ammonia as their electron-donating
      counterpart. We have derived an unoccupied reactive orbital that shows the
      maximum localization on the Ga atomic center for each species. The orbital is
      located lower in energy compared to those in the corresponding boron and aluminum
      halides. In contrast to boron halides, the unoccupied reactive orbital of the
      acid site tends to be delocalized considerably on the halogens as the fluorines
      are substituted by chlorines in gallium halides. The trend observed in the
      effects of fluorine and chlorine on the acidity of the gallium halides is
      opposite to those found in the boron halides. This cannot be interpreted solely
      in terms of the electron-accepting strength of the gallium center, but can be
      understood by including electrostatic interactions and closed-shell repulsion
      with ammonia in the adducts. The origin of the difference in Lewis acidity of
      BCl(3), AlCl(3), and GaCl(3) has been clarified.

PMID- 12230393
TI  - New Cd(II)-, Co(II)-, and Cu(II)-containing coordination polymers synthesized by
      using the rigid ligand 1,2-bis(3-pyridyl)ethyne (3,3'-DPA).
AB  - Four new organic/inorganic coordination polymers,
      [Cd(C(10)H(8)N(2))(2)(H(2)O)(2)(NO(3))(2)](n)(1),
      [Co(C(10)H(8)N(2))(H(2)O)NO(3)CH(3)OH](n)(2),
      [Cu(C(10)H(8)N(2))(CH(3)OH)(NO(3))(2)](n) (3), and
      [Cu(C(10)H(8)N(2))(hfac)(2)](n)(4), were synthesized by using the rigid ligand
      1,2-bis(3-pyridyl)ethyne (3,3'-DPA). Complex 1 crystallizes in space group P2/n:
      a = 12.462(2) A, b = 9.485(1) A, c = 13.383(2) A, beta = 96.629(2) degrees, V =
      1559.6(3) A(3), Z = 4. Complex 2 crystallizes in space group Fddd: a = 9.248(4)
      A, b = 19.982(7) A, c = 35.093(16) A, V = 6485.0(4) A(3), Z = 8. Complex 3
      crystallizes in space group I2/a: a = 18.315(2) A, b = 8.517(1) A, c = 20.494(3)
      A, beta = 104.042(2) degrees, V = 3101.2(7) A(3), Z = 8. Complex 4 crystallizes
      in space group P21/c: a = 6.576(1) A, b = 16.189(1) A, c = 11.653(1) A, beta =
      91.337(1) degrees, V = 1240.3(2) A(3), Z = 2. The coordination polymers display a
      variety of structural architectures, ranging from sinusoidal and zigzag chains
      (1, 3, 4) to two-dimensional channel-type architectures (2). The effects of the
      orientation of the nitrogen atom in the pyridine rings on the resultant
      structures are discussed.

PMID- 12230394
TI  - First Cu(II) diamondoid net with 2-fold interpenetrating frameworks. The role of
      anions in the construction of the supramolecular arrays.
AB  - The synthesis and crystal structure of the three-dimensional coordination polymer
      of an angular dipyridyl ligand 2,5-bis(4-pyridyl)-1,3,4-oxadiazole (L) and
      Cu(ClO(4))(2), exhibiting the first Cu(II) diamondoid network with 2-fold
      interpenetration, ([Cu(L)(2)(H(2)O)(2)](ClO(4))(OH)(H(2)O)(2.5))(n) (1), together
      with the Cu(OAc)(2) complex of L, [Cu(L)(2)(OAc)(2)(H(2)O)](H(2)O)(2)(CH(3)OH)
      (2), with an unexpected mononuclear structure, are reported. Crystal data for 1:
      tetragonal, space group I4(1)/a, a = b = 13.477(3) A, c = 46.167(13) A, Z = 8.
      Crystal data for 2: triclinic, space group P(-)1, a = 7.847(2) A, b = 13.189(4)
      A, c = 15.948(5) A, alpha = 75.225(7) degrees, beta = 79.945(6) degrees, gamma =
      77.540(5) degrees, Z = 2. The magnetic properties and anion effect are also
      discussed.

PMID- 12230395
TI  - [Ag(2)(C(33)H(26)N(2)O(2))(H(2)O)(2)(SO(3)CF(3))(2)].0.5C(6)H(6): a luminescent
      supramolecular silver(I) complex based on metal-carbon and metal-heteroatom
      interactions.
AB  - A novel fulvene-type bidentate ligand 1 has been synthesized by an aroylation
      reaction of cyclohexyl-substituted cyclopentadienyl anions. Compound 1
      crystallizes in the triclinic space group P(-)1, with a = 7.0419(5) A, b =
      11.9360(8) A, c = 15.6470(11) A, alpha = 85.1440(10) degrees, beta = 78.1140(10)
      degrees, gamma = 74.5360(10) degrees, V = 1239.76(15) A(3), and Z = 2. The
      coordination chemistry of 1 was investigated, and a novel Ag-containing
      coordination polymer (2), linked by both Ag-heteroatom and Ag-carbon
      interactions, has been synthesized. The coordination polymer has been fully
      characterized by infrared spectroscopy, elemental analysis, and single-crystal X
      ray diffraction. Compound 2 crystallizes in the triclinic space group P(-)1, with
      a = 7.1654(5) A, b = 15.7277(11) A, c = 18.8157(13) A, alpha = 73.5150(10)
      degrees, beta = 89.0410(10) degrees, gamma = 89.0970(10) degrees, V = 1355.19(14)
      A(3), and Z = 2. The solid-state structure of 2 features a one-dimensional double
      chain motif. These double chains are in turn cross-linked to each other via
      strong interchain O-H...O hydrogen bonds, forming a novel two-dimensional network
      with remarkably large cavities (effective cross section of ca. 21 x 15 A) that
      are occupied by benzene guest molecules. Both compounds 1 and 2 are luminescent
      in the solid state, and a large blue-shift in the emission between the free
      ligand 1 and the ligand incorporated into complex 2 is observed.

PMID- 12230396
TI  - Organometallic Pt(II) compounds. A complementary study of a triplet emitter based
      on optical high-resolution and optically detected magnetic resonance
      spectroscopy.
AB  - The emitting triplet state of cyclometalated Pt(thpy)(CO)(Cl) monomers ((thpy)(-)
      = 2-(2'-thienylpyridinate), frequently also abbreviated as (2-thpy)(-)) is
      investigated at T = 1.2 K (typically) by use of the complementary methods of high
      resolution optical spectroscopy and of optically detected magnetic resonance
      (ODMR) spectroscopy. Such a complimentary investigation is carried out for the
      first time for a Pt(II) compound. In solution, oligomer or short linear chain
      formation is also observed. However, the monomers can be investigated
      selectively, when they are dissolved in a relatively inert n-octane matrix
      (Shpol'skii matrix). This allows us to determine the energies of the T(1) triplet
      substates I, II, and III relative to the electronic ground state S(0)(0), the
      zero-field splittings (ZFSs) of T(1), and emission decay time constants (I/II <-
      > 0, 18012.5 cm(-1); III <--> 0, 18016.3 cm(-1); DeltaE(I,II) = 0.05437 cm(-1)
      (1.631 GHz), DeltaE(I,III) = 3.8 cm(-1) (114 GHz); tau(I) = 120 micros, tau(II) =
      45 micros, tau(III) = 35 micros; spin-lattice relaxation time for the processes
      III --->I/II, tau(SLR) = 3.0 micros). The vibrational satellite structure
      observed in the emission of the T(1) state to the singlet ground state S(0) is
      also discussed. Moreover, it is possible to estimate the intersystem crossing
      time from the excited singlet state S(1) at 22952 cm(-1) to the triplet state
      T(1) to approximately 5 ps. The T(1) state is assigned as a thpy-ligand-centered
      (3)pipi* state with small metal-to-ligand charge-transfer (MLCT) admixtures. A
      comparison of Pt(thpy)(CO)(Cl) to a series of other organometallic Pt(II)
      compounds, such as heteroleptic Pt(ppy)(CO)(Cl) ((ppy)(-) = phenylpyridinate),
      Pt(dppy)(CO) ((dppy)(2-) = diphenylpyridinate), and Pt(i-biq)(CN)(2) (i-biq =
      2,2'-bisisoquinoline) and homoleptic Pt(thpy)(2) and Pt(ppy)(2), is carried out.
      (The structures are shown in Figure 7.) Trends of photophysical properties are
      discussed. In particular, by chelation of two equal ligands the pattern of ZFS is
      strongly altered, resulting in a significant increase of the MLCT participation
      in the lowest triplet state of these organometallic compounds. This new
      observation represents an interesting further step concerning chemical tunability
      of photophysical properties.

PMID- 12230397
TI  - Factors influencing conformer equilibria in retro models of cisplatin-DNA adducts
      as revealed by moderately dynamic (N,N'-dimethyl-2,3-diaminobutane)PtG(2) retro
      models (G = a guanine derivative).
AB  - Typical cis-PtA(2)G(2) models of key DNA lesions formed by cis-type Pt anticancer
      drugs are very dynamic and difficult to characterize (A(2) = diamine or two
      amines; G = guanine derivative). Retro models have A(2) carrier ligands designed
      to decrease dynamic motion without eliminating any of three possible conformers
      with bases oriented head-to-tail (two: DeltaHT and LambdaHT) or head-to-head
      (one: HH). All three were found in NMR studies of eight Me(2)DABPtG(2) retro
      models (Me(2)DAB = N,N'-dimethyl-2,3-diaminobutane with S,R,R,S and R,S,S,R
      configurations at the chelate ring N, C, C, and N atoms, respectively; G = 5'
      GMP, 3'-GMP, 5'-IMP, and 3'-IMP). The bases cant to the left (L) in (S,R,R,S)
      Me(2)DABPtG(2) adducts and to the right (R) in (R,S,S,R)-Me(2)DABPtG(2) adducts.
      Relative to the case in which the bases are both not canted, canting will move
      the six-membered rings closer in to each other ("6-in" form) or farther out from
      each other ("6-out" form). Interligand interactions between ligand components
      near to Pt (first-first sphere communication = FFC) or far from Pt (second-sphere
      communication = SSC) influence stability. In typical cases at pH < 8, the "6-in"
      form is favored, although the larger six-membered rings of the bases are close.
      In minor "6-out" HT forms, the proximity of the smaller five-membered rings could
      be sterically favorable. Also, G O6 is closer to the sterically less demanding NH
      part of the Me(2)DAB ligand, possibly allowing G O6-NH hydrogen bonding. These
      favorable FFC effects do not fully compensate for possibly stronger FFC dipole
      effects in the "6-in" form. SSC, phosphate-N1H cis G interactions favor LambdaHT
      forms in 5'-GMP and 5'-IMP complexes and DeltaHT forms in 3'-GMP and 3'-IMP
      complexes. When SSC and FFC favor the same HT conformer, it is present at >90%
      abundance. In six adducts [four (S,R,R,S)-Me(2)DABPtG(2) and (R,S,S,R)
      Me(2)DABPtG(2) (G = 3'-GMP and 3'-IMP)], the minor "6-out" HT form at pH
      approximately 7 becomes the major form at pH approximately 10, where G N1H is
      deprotonated, because the large distance between the negatively charged N1 atoms
      minimizes electrostatic repulsion and probably because the G O6-(NH)Me(2)DAB H
      bond (FFC) is strengthened by N1H deprotonation. At pH approximately 10,
      phosphate-negative N1 repulsion is an unfavorable SSC term. This factor disfavors
      the LambdaHT R form of two (R,S,S,R)-Me(2)DABPtG(2) (G = 5'-GMP and 5'-IMP)
      adducts to such an extent that the "6-in" DeltaHT R form remains the dominant
      form even at pH approximately 10.

PMID- 12230398
TI  - Lanthanide-transition-metal carbonyl complexes. 1. Syntheses and structures of
      ytterbium(II) solvent-separated ion pairs and isocarbonyl polymeric arrays of
      tetracarbonylcobaltate.
AB  - Transmetalation reactions of metallic ytterbium with Hg[Co(CO)(4)](2) in the
      coordinating solvents pyridine and THF yield the solvent-separated ion pairs
      [Yb(L)(6)] [Co(CO)(4)](2) (1a, L = Pyr; 2a, L = THF). The IR spectrum of 1a in
      pyridine indicates that the tetracarbonylcobaltate anion is not directly bonded
      to the divalent Yb cation owing to the strong coordinating ability of pyridine.
      On the other hand, IR spectra of 2a in THF are concentration dependent. In dilute
      solutions there is an equilibrium between the solvent-separated ion pair and a
      weak contact ion pair. Higher concentrations of 2a facilitate the formation of a
      tight ion pair that has a low-frequency isocarbonyl absorption. Remarkably,
      complexes 1a and 2a are easily transformed in toluene into the two-dimensional
      sheetlike arrays [(Pyr)(4)Yb[(mu-CO)(2)Co(CO)(2)](2)](infinity) (1b) and
      [(THF)(2)Yb[(mu-CO)(3)Co(CO)](2).Tol](infinity) (2b). The two-dimensional
      frameworks are supported by isocarbonyl linkages. Infrared spectra of toluene
      solutions substantiate the existence of the isocarbonyl bridges with low
      frequency absorptions at 1780 cm(-1). Compounds 1b and 2b belong to a rare class
      of lanthanide-transition-metal carbonyl extended arrays, only three others of
      which have been structurally established. Dissolving 1b in pyridine regenerates
      1a, but the complete conversion of 2b into 2a cannot be achieved. Crystal data:
      1a.Pyr is monoclinic, P2(1)/c, a = 11.171(1) A, b = 11.925(1) A, c = 33.978(1) A,
      beta = 95.10(1) degrees, Z = 4; 2a is monoclinic, C2/c, a = 17.724(1) A, b =
      12.468(1) A, c = 18.413(1) A, beta = 100.34(1) degrees, Z = 4; 1b is monoclinic,
      C2/c, a = 11.047(1) A, b = 13.423(1) A, c = 21.933(1) A, beta = 103.49(1)
      degrees, Z = 4; 2b is monoclinic, C2/c, a = 28.589(1) A, b = 7.223(1) A, c =
      14.983(1) A, beta = 118.90(1) degrees, Z = 4.

PMID- 12230399
TI  - Diastereoisomeric singly bridged cyclophosphazene-macrocyclic compounds.
AB  - 31P NMR spectroscopy and added chiral shift reagent (CSR) or chiral solvating
      agent (CSA) have been used to show that unsymmetrically substituted singly
      bridged macrocyclic phosphazene compounds exist as 1:1 diastereoisomers of two
      racemic mixtures, in contrast to previous work (ref 2) on symmetrically
      substituted diastereoisomeric analogues, which exist as meso and racemic forms.
      The cis-ansa cyclotriphosphazatriene-macrocycle, 1, is meso and monosubstitution
      of the >P(O-macrocycle)Cl group with 2-naphthol gives a racemic product (7), in
      which the macrocyclic ring exists in a trans-ansa configuration. Reaction of 7
      with the di-secondary amine, piperazine, gives an unsymmetrically disubstituted
      racemic compound (8) having a cis-ansa configuration of the macrocyclic ring.
      Reaction of 8 with a further quantity of 1 forms a singly bridged derivative (9)
      with the macrocyclic rings in cis-trans configurations, and further reaction of 9
      with pyrrolidine gives compound 10 with the macrocyclic rings in cis-cis
      configurations. Both 9 and 10 have four stereogenic centers giving rise to
      diastereoisomeric compounds existing as mixtures of two racemates. The results
      are consistent with inversion of configuration at phosphorus at each step of the
      reaction of >P(OR)Cl groups with nucleophile Z (i.e., Z = naphthoxy, piperazino,
      pyrrolidino) to form >P(OR)Z derivatives.

PMID- 12230400
TI  - Matrix reactivity of AlF and AlCl in the presence of HCl and HBr: generation and
      characterization of the new Al(III) hydrides HAlFCl, HAlFBr, and HAlClBr and the
      monomeric mixed Al(III) halides AlX(2)Y (X, Y = F, Cl, or Br).
AB  - The spontaneous and photolytically induced reactions of AlF and AlCl in the
      presence of HCl and HBr in solid argon matrices were followed and the products
      identified and characterized by means of IR spectroscopy. Quantum mechanical
      calculations allow for a further evaluation of the properties of the reaction
      products. These are the adducts AlF.HCl, AlF.HBr, and AlCl.HBr, representing the
      products of spontaneous reactions, and the trivalent Al(III) hydrides HAlFCl,
      HAlFBr, and HAlClBr, which were formed upon photoactivation of these complexes.
      All three hydrides are planar molecules (C(s)() symmetry) with bond angles in
      agreement with the predictions of the VSEPR theory. In addition, the mixed
      halides AlFCl(2), AlFBr(2), and AlClBr(2) were formed upon photolysis. The
      bisadducts AlF.(HCl)(2) and AlF.(HBr)(2) are likely to be the precursors to these
      species.

PMID- 12230401
TI  - Novel intramolecular C-H bond activation in an iridium dppm complex.
AB  - Reaction of TpIr(C(2)H(4))(2) (Tp = tris-pyrazolylborate) with various chelating
      phosphine ligands has been explored. Reaction with bis-diphenylphosphinoethane
      leads to complete displacement of the Tp ligand. With bis
      diphenylphosphinomethane, an intramolecular proton transfer from the methylene
      bridge to the iridium center occurs to give an iridium hydride complex formally
      resulting from oxidative C-H bond activation. Reaction with 2,2
      bis(diphenylphosphino)propane (dppip) affords an Ir(I) complex formulated as
      kappa(2)-TpIr(dppip). Protonation of this Ir(I) complex gives a six coordinate
      Ir(III) hydride species.

PMID- 12230402
TI  - Variation in the coordination mode of arenedisulfonates: syntheses and structural
      characterization of mononuclear and dinuclear cadmium(II) arenedisulfonate
      complexes with two- to zero-dimensional architectures.
AB  - Seven cadmium(II) arenedisulfonate compounds, namely [Cd(2,2'
      bpy)(2)(H(2)O)(peds)].4H(2)O (1), [Cd(2)(2,2'
      bpy)(4)(H(2)O)(2)(1,5nds)](1,5nds).4H(2)O (2), [Cd(cyclam)(1,5nds)](2) (3),
      ([Cd(inia)(2)(H(2)O)(2)(2,6nds)].4H(2)O)(n)(4),
      ([Cd(inia)(2)(H(2)O)(2)(bpds)].4H(2)O)(n)(5),
      ([Cd(2)(inia)(4)(H(2)O)(3)(peds)(2)].2H(2)O)(n)(6), and [Cd(1,5nds)(H(2)O)(2)](n)
      (7), where 2,2'-bpy = 2,2'-bipyridyl, cyclam = 1,4,8,11-tetraazacyclotetradecane,
      inia = isonicotinamide, nds = naphthalenedisulfonate, bpds = 4,4'
      biphenyldisulfonate, and peds = 4,4'-phenyletherdisulfonate, have been obtained
      from aqueous solution by using similar procedures and structurally characterized
      by X-ray single-crystal diffraction, IR spectroscopy, and thermal gravimetric
      analysis. In 1, the peds anion coordinates as a monodentate ligand, leading to a
      mononuclear unit. In 2 and 3, the 1,5nds anions coordinate as mu(2)-bridging
      ligands in different modes, producing charged or neutral dinuclear clusters. In 4
      and 5, 2,6nds and bpds behave as mu(2)-spacers, resulting in 1-dimensional
      polymers. While in 6, the peds acts both as terminal and bridging ligands with
      the SO(3)(-) groups being either monodentate or mu(2)-bridging, creating a
      knotted 1-dimensional polymer with dinuclear clusters as the repeating units. In
      7, 1,5nds acts as a bridging ligand with each SO(3)(-) coordinated as a mu(2)
      bridging group to adjacent Cd(II) centers, leading to a 2-dimensional polymer.
      Together with the reported ([Cu(en)(2)(1,5nds)].2H(2)O)(n) (8), all of the six
      possible coordination modes adopted by organodisulfonate anions, on the
      assumption that each SO(3)(-) group could be monodentate or mu(2)-bridging, are
      realized by introducing nitrogen-containing organic ligands as auxiliaries.

PMID- 12230403
TI  - The cyclopentenone product of lipid peroxidation, 15-A(2t)-isoprostane (8
      isoprostaglandin A(2)), is efficiently conjugated with glutathione by human and
      rat glutathione transferase A4-4.
AB  - Glutathione transferases (GSTs) are a large family of enzymes that can be divided
      into different classes based on structure. There has been considerable interest
      in the ability of GSTs to conjugate and inactivate endogenously derived reactive
      lipid peroxidation products that contain alpha,beta-unsaturated carbonyl moieties
      such as 4-hydroxyalkenals. One enzyme with prominent activity toward these
      substrates is human GST A4-4. Recently, we described a novel series of compounds
      termed A(2)/J(2)-isoprostanes (IsoPs) that are formed endogenously in humans from
      the free radical-initiated peroxidation of arachidonic acid. These compounds
      contain alpha,beta-unsaturated carbonyl groups and have structures similar to
      cyclooxygenase-derived PGA(2) and PGJ(2). Because of their chemical reactivity,
      these compounds may mediate tissue injury associated with oxidant stress. Herein,
      we report that the A-ring IsoP 15-A(2t)-IsoP (8-iso-PGA(2)) is efficiently
      conjugated to glutathione (GSH) by human GST A4-4 with a k(cat)/K(m) value of
      >200 s(-)(1) mM(-)(1). The k(cat)/K(m) value for conjugation of 15-A(2t)-IsoP by
      the homologous rat GST A4-4 is >2000 s(-)(1) mM(-)(1). Similar high enzyme
      activities were observed when PGA(2) was used as a substrate. In contrast, the
      human GSTs A1-1, M1-1, M2-2, P1-1, and T1-1 and rat GST T2-2 did not
      significantly metabolize 15-A(2t)-IsoP. These studies have therefore defined a
      potentially important route by which cyclopentenone IsoPs are metabolized that
      may serve as a mechanism for the inactivation of these highly reactive compounds.

PMID- 12230404
TI  - Manganese oxidation state and its implications for toxicity.
AB  - Manganese (Mn) is ubiquitous in mammalian systems and is essential for proper
      development and function, though it can also be toxic at elevated exposures.
      While essential biologic functions of Mn depend on its oxidation state [e.g.,
      Mn(II), Mn(III)], little is known about how the oxidation state of elevated Mn
      exposures affect cellular uptake, and function/toxicity. Here we report the
      dynamics of EPR measurable Mn(II) in fresh human plasma and cultured PC12 cell
      lysates as a function of exposure to either manganese(II) chloride or
      manganese(III) pyrophosphate, and the effects of exposure to Mn(II) versus
      Mn(III) on total cellular aconitase activity and cellular Mn uptake. The results
      indicate that Mn(II) or Mn(III) added in vitro to fresh human plasma or cell
      lysates yielded similar amounts of EPR measurable Mn(II). In contrast, Mn added
      as Mn(III) was significantly more effective in inhibiting total cellular
      aconitase activity, and intact PC12 cells accumulated significantly more Mn when
      exposures occurred as Mn(III). Collectively, these data reflect the dynamic
      nature of Mn speciation in simple biological systems, and the importance of Mn
      oxidation/speciation state in mediating potential cellular toxicity. This study
      supports concern over increased environmental exposures to Mn in different
      oxidation states [Mn(II), Mn(III), and Mn(IV)] that may arise from combustion
      products of the gasoline antiknock additive methycyclopentadienyl manganese
      tricarbonyl (MMT).

PMID- 12230405
TI  - Cytochrome P450 1B1 determines susceptibility to dibenzo[a,l]pyrene-induced tumor
      formation.
AB  - Metabolic activation, DNA binding, and tumorigenicity of the carcinogenic
      polycyclic aromatic hydrocarbon dibenzo[a,l]pyrene (DB[a,l]P) catalyzed by murine
      cytochrome P450 (P450) enzymes were investigated. DNA binding of DB[a,l]P in
      human mammary carcinoma MCF-7 and human P450-expressing Chinese hamster V79 cell
      lines was previously shown to occur preferentially with metabolically generated
      fjord region DB[a,l]P-11,12-dihydrodiol 13,14-epoxides (DB[a,l]PDE). To elucidate
      different capabilities of murine P450 1A1 and 1B1 for metabolic activation of
      DB[a,l]P, V79 cell cultures stably expressing P450s 1A1 or 1B1 from mice were
      exposed to 10 or 100 nM DB[a,l]P. Both cell lines transformed DB[a,l]P to DNA
      binding intermediates. As with V79 cells expressing the corresponding human P450
      enzyme [Luch et al. (1998) Chem. Res. Toxicol. 11, 686-695], murine P450 1B1
      catalyzed metabolism and DNA binding proceeded exclusively through generation of
      fjord region DB[a,l]PDE. In addition, only DB[a,l]PDE-derived DNA adducts were
      found in V79 cells expressing P450 1A1 from mice. This is in contrast to our
      recent findings with V79 cells expressing P450 1A1 from humans or rats which
      catalyzed the formation of both highly polar DNA adducts as well as nonpolar
      DB[a,l]PDE-DNA adducts. To establish the role of P450 1B1 in DB[a,l]P-induced
      tumor formation in vivo, we treated P450 1B1-null and wild-type mice
      intragastrically and monitored survival rates and appearance of neoplasias in
      various organs. All wild-type mice (n = 17) used in this study developed at least
      one tumor at one site (tumor rate of 100%). In contrast, 5 of 13 P450 1B1-null
      mice were observed to be free from any tumor (tumor rate of 62%). The organ sites
      of tumor formation and the dignity of tumors were different between wild-type and
      P450 1B1-null mice. Wild-type mice were diagnosed with both benign and malignant
      tumors of the ovaries, lymphoid tissues, as well as with skin and endometrial
      hyperplasias, whereas P450 1B1-null mice developed only lung adenomas and
      endometrial hyperplasias. DNA binding studies using embryonic fibroblasts
      isolated from these animals provided further evidence that P450 1B1-catalyzed
      formation of fjord region DB[a,l]PDE-DNA adducts is the critical step in DB[a,l]P
      mediated carcinogenesis in mice, and probably also in man.

PMID- 12230406
TI  - NMR-based metabonomic studies on the biochemical effects of commonly used drug
      carrier vehicles in the rat.
AB  - The biochemical effects of a series of commonly used drug carrier vehicles were
      investigated using (1)H NMR spectroscopic and pattern recognition based
      metabonomic analysis. Animals were treated by oral gavage with six dosage
      vehicles: 0.5% (w/v) sodium carboxymethylcellulose/0.2% (v/v)tween; microemulsion
      (consisting of propylene glycol, ethanol, cremophor, and corn oil glycerides);
      labrafil [consisting of poly(ethylene glycol) 300 esterified with oleic acid]
      (30%)/corn oil (70%); 0.1 M sodium phosphate buffered water; poly(ethylene
      glycol) 300 and 0.5% methocel. Urine samples (n = 7) collected over a 96 h period
      post administration were analyzed using 600 MHz (1)H NMR spectroscopy, and
      principal components analysis of the spectral data was used to analyze these
      data. Of the six vehicles studied, three (labrafil/corn oil, PEG 300 and
      microemulsion) gave rise to strong vehicle-related signals in the (1)H NMR
      spectra of urine and were, therefore, deemed to be less suitable for NMR-based
      toxicity studies. To investigate any biochemical consequences of vehicle dosing,
      PCA was used to analyze spectral regions that did not contain vehicle-related
      signals, i.e., the NMR-detectable endogenous metabolite profile. PEG 300 and
      labrafil/corn oil induced changes in the biochemical composition of urine
      including increased concentrations of dicarboxylic acids, creatinine, taurine,
      and sugars, indicating that these vehicles were bioactive in their own right and
      that this might confound interpretation of biochemical effects of weakly toxic
      drugs dosed in these carriers. This study shows the importance of selecting
      appropriate vehicles for NMR-based metabonomic studies with a view to minimizing
      the possibility of vehicle resonances obscuring endogenous compound peaks.
      Furthermore, we have shown that at least two of the commonly used drug carrier
      vehicles caused metabolic perturbations in the urine profile. These alterations
      in the biochemical profile reflect vehicle-induced changes in the physiological
      status of the organism that may obscure the pharmacologic or toxicologic effects
      of drugs.

PMID- 12230407
TI  - Type II guanine oxidation photoinduced by the antibacterial fluoroquinolone
      Rufloxacin in isolated DNA and in 2'-deoxyguanosine.
AB  - The role played by type I (radical) and type II (singlet oxygen) mechanisms in
      the Rufloxacin (RFX)-photoinduced production of 8-hydroxy-2'-deoxyguanosine in
      DNA has been evaluated. This fluoroquinolone drug has been shown to be able to
      photoinduce increased levels of some DNA base oxidation products, such as 8-OH
      dGuo, that are indicative of mutagenic and carcinogenic events, with probable
      implications in aging processes. The relative weight of the two
      photosensitization mechanisms was obtained via determination of two different
      photoproducts of 2'-deoxyguanosine (dGuo), which are diagnostic of the two
      different pathways, namely, (4R)- and (4S)-4,8-dihydro-4-hydroxy-8-oxo-2'
      deoxyguanosine and 2,2-diamino-4-[(2-deoxy-beta-D-erythro-pentofuranosyl)amino]
      2,5-dihydrooxazol-5-one. The observed predominance of type II reaction is in
      agreement with the fact that the triplet state of RFX is able to transfer with
      high efficiency its energy to molecular oxygen, giving rise to singlet oxygen.
      Photophysical measurements suggest that hydrated electrons produced by Rufloxacin
      photoionization react with dGuo, Thd, and DNA, whereas these biomolecules quench
      the RFX triplet state with low efficiency. Static quenching of Rufloxacin
      fluorescence indicates an interaction of this drug both with DNA and with dGuo.
      On the basis of these experimental data, Rufloxacin photosensitization of DNA is
      proposed to occur by a type II mechanism.

PMID- 12230408
TI  - Possible role of dimethylarsinous acid in dimethylarsinic acid-induced urothelial
      toxicity and regeneration in the rat.
AB  - Dimethylarsinic acid (DMA(V)) is carcinogenic to the rat urinary bladder when
      administered at high doses in the diet or drinking water. At a dietary dose of
      100 ppm (microg/g), it produces cytotoxicity within 6 h and increased
      proliferation (hyperplasia) by 7 days of administration. We hypothesize that
      formation of the reactive organic intermediate dimethylarsinous acid (DMA(III))
      is involved in the induction of the cytotoxicity. To evaluate the possibility
      that DMA(V) administration produces urothelial toxicity and regeneration by the
      formation of trivalent arsenicals, 2,3-dimercaptopropane-1-sulfonic acid (DMPS,
      5600 ppm), a chelator of trivalent arsenicals, was co-administered with DMA(V)
      (100 ppm) for 2 weeks to groups of female Fischer F344 rats. Based on light and
      scanning electron microscopy, and bromodeoxyuridine labeling index, DMA(V)
      produced cytotoxicity and regenerative hyperplasia of the urothelium which was
      inhibited by co-administration with DMPS. The major forms of arsenic in the 24-h
      urine of rats administered DMA(V) were high concentrations of DMA(V) (66.4 +/-
      2.7 microM) itself and the pentavalent organic arsenical trimethylarsine oxide
      (TMAO) (73.2 +/- 9.5 microM). Co-administration with DMPS led to an increase in
      DMA(V) (507 +/- 31 microM) with a decrease in TMAO (2.8 +/- 0.4 microM)
      excretion. The formation of TMAO from DMA(V) mechanistically suggests formation
      of the intermediate trivalent metabolite, DMA(III). In a second experiment
      evaluating fresh void urines collected on study days 1, 71, and 175, we detected
      DMA(III) in the urine of DMA(V) and DMA(V) plus DMPS-treated rats at
      approximately micromolar concentrations. Using rat (MYP3) and human (1T1)
      urothelial cells, cytotoxicity for trivalent arsenicals, sodium arsenite,
      monomethylarsonous acid (MMA(III)), and DMA(III) was demonstrated at 0.4-4.8
      microM concentrations, whereas MMA(V), DMA(V), and TMAO were cytotoxic at
      millimolar concentrations. The presence of DMA(III) at micromolar concentrations
      in the urine of rats fed 100 ppm DMA(V) suggests that DMA(III) produced in vivo
      may be involved in the toxic effects in the rat urinary bladder after dietary
      administration of DMA(V).

PMID- 12230409
TI  - Neonicotinoid insecticides: reduction and cleavage of imidacloprid nitroimine
      substituent by liver microsomal and cytosolic enzymes.
AB  - The major insecticide imidacloprid (IMI) is known to be metabolized by human
      cytochrome P450 3A4 with NADPH by imidazolidine hydroxylation and dehydrogenation
      to give 5-hydroxy-imidacloprid and the olefin, respectively, and by nitroimine
      reduction and cleavage to yield the nitrosoimine, guanidine, and urea
      derivatives. More extensive metabolism by human or rabbit liver microsomes with
      NADPH or rabbit liver cytosol without added cofactor reduces the IMI N-nitro
      group to an N-amino substituent, i.e., the corresponding hydrazone. A major
      metabolite on incubation of IMI in the human microsome-NADPH system is
      tentatively assigned by LC/MS as a 1,2,4-triazol-3-one derived from the
      hydrazone; the same product is obtained on reaction of the hydrazone with ethyl
      chloroformate. The hydrazone and proposed triazolone are considered here together
      (referred to as the hydrazone) for quantitation. Only a portion of the microsomal
      reduction and cleavage of the nitroimine substituent is attributable to a CYP450
      enzyme. The cytosolic enzyme conversion to the hydrazone is inhibited by added
      cofactors (NAD > NADH > NADP > NADPH) and enhanced by an argon instead of an air
      atmosphere. The responsible cytosolic enzyme(s) does not appear to be DT
      diaphorase (which is inhibited by several neonicotinoids), aldose reductase,
      aldehyde reductase, or xanthine oxidase. However, the cytosolic metabolism of IMI
      is inhibited by several aldo-keto-reductase inhibitors (i.e., alrestatin, EBPC,
      Ponalrestat, phenobarbital, and quercetin). Other neonicotinoids with nitroimine,
      nitrosoimine, and nitromethylene substituents are probably also metabolized by
      "neonicotinoid nitro reductase(s)" since they serve as competitive substrates for
      [(3)H]IMI metabolism.

PMID- 12230410
TI  - Surface modification of quartz inhibits toxicity, particle uptake, and oxidative
      DNA damage in human lung epithelial cells.
AB  - Quartz (crystalline silica) is not consistently carcinogenic across different
      industries where similar quartz exposure occurs. In addition, there are reports
      that surface modification of quartz affects its cytotoxicity, inflammogenicity,
      and fibrogenicity. Taken together, these data suggest that the carcinogenicity of
      quartz is also related to particle surface characteristics, and so we determined
      the genotoxic effects of DQ12 quartz particles versus DQ12 whose surface was
      modified by treating with either aluminum lactate or polyvinylpyridine-N-oxide
      (PVNO). The different particle preparations were characterized for hydroxyl
      radical generation using electron spin resonance (ESR). DNA damage was determined
      by immunocytochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG) and the
      alkaline comet-assay using A549 human lung epithelial cells. Cytotoxicity was
      measured using the LDH- and MTT-assays, and particle uptake by the A549 cells was
      quantified by light microscopy, using digital light imaging evaluation of 800 nm
      sections. The ability of quartz to generate hydroxyl-radicals in the presence of
      hydrogen peroxide was markedly reduced upon surface modification with aluminum
      lactate or PVNO. DNA strand breakage and 8-OHdG formation, as produced by quartz
      at nontoxic concentrations, could be completely prevented by both coating
      materials. Particle uptake into A549 cells appeared to be significantly inhibited
      by the PVNO-coating, and to a lesser extent by the aluminum-lactate coating. Our
      data demonstrate that respirable quartz particles induce oxidative DNA damage in
      human lung epithelial cells and indicates that surface properties of the quartz
      as well as particle uptake by these target cells are important in the cytotoxic
      and the genotoxic effects of quartz in vitro.

PMID- 12230411
TI  - Evaluation of commercial ginkgo and echinacea dietary supplements for colchicine
      using liquid chromatography-tandem mass spectrometry.
AB  - In response to concerns that commercial dietary supplements containing Ginkgo
      biloba (ginkgo) and Echinacea purpurea, Echinacea angustifolia, or Echinacea
      pallida (echinacea) might be contaminated with colchicine, a highly selective and
      sensitive assay was developed for colchicine that is based on high-performance
      liquid chromatography-tandem mass spectrometry (LC-MS-MS). The method utilizes
      reversed-phase HPLC separation of compounds in a methanolic extract of the
      dietary supplement or botanical sample followed by positive ion electrospray
      ionization with collision-induced dissociation and multiple reaction monitoring
      of three characteristic fragmentation pathways of the protonated molecule of
      colchicine, m/z 400 --> 358, 400 --> 326, and 400 --> 310. The minimal detectable
      concentration of colchicine using this assay was 10 pg on-column, which is
      equivalent to 20 ppb colchicine in a 0.5 g ginkgo leaf sample. The method was
      validated by analyzing 0.5 g samples spiked with colchicine and determining the
      recovery. A total of 26 commercial ginkgo and echinacea dietary supplements were
      purchased from pharmacies in Chicago, IL, and analyzed for colchicine. In
      contrast to a recent report, no colchicine was detected in any of the samples. In
      addition, authenticated ginkgo leaves were collected, assayed, and found to
      contain no colchicine, which is consistent with the botanical literature. On the
      basis of the results obtained using this new LC-MS-MS assay, which is more
      sensitive and more selective than previously published methods for colchicine, we
      find no cause for concern regarding colchicine contamination of ginkgo or
      echinacea dietary supplements.

PMID- 12230412
TI  - Doxorubicin-dependent reduction of ferrylmyoglobin and inhibition of lipid
      peroxidation: implications for cardiotoxicity of anticancer anthracyclines.
AB  - Lipid peroxidation has been proposed to mediate cardiotoxicity induced by
      doxorubicin (DOX) and other anticancer anthracyclines; however, there have been
      reports showing that DOX can also inhibit lipid peroxidation. Here we
      characterized the effects of DOX on the oxo-ferryl moiety [Fe(IV)=O, Mb(IV)] of
      H(2)O(2)-activated myoglobin, a lipid oxidant likely formed in the heart during
      treatment with DOX. Mb(IV) was formed in vitro by reacting 100 microM H(2)O(2)
      with 50 microM horse heart metmyoglobin (Mb(III)). Spectral studies showed that
      DOX reduced Mb(IV) to Mb(III), half-maximal regeneration of Mb(III) occurring at
      approximately 18 microM DOX. Comparisons between DOX, its aglycone
      doxorubicinone, and other approved or investigational anthracyclines or model
      compounds (daunorubicin, idarubicin, aclarubicin, and naphthazarin), showed that
      DOX reduced Mb(IV) through the hydroquinone moiety of its tetracyclic ring. DOX
      inhibited Mb(IV)-dependent peroxidation of arachidonic acid, suppressing the
      formation of thiobarbituric acid-reactive substances with an IC(50) of
      approximately 18 microM. Lipid peroxidation was inhibited also by the
      hydroquinone-containing daunorubicin and idarubicin but not by the hydroquinone
      deficient aclarubicin; moreover, neither simple hydroquinone nor other known
      Mb(IV) reductants (ascorbate, glutathione, and ergothioneine) reached measurable
      IC(50)s in a micromolar range. DOX-dependent inhibition of lipid peroxidation
      correlated with its ability to reduce Mb(IV) to Mb(III) in competition with
      arachidonic acid (r = 0.83, P = 0.029); it did not correlate with its ability to
      scavenge other free radical species [like e.g., peroxyl radicals generated
      through the thermal decomposition of 2,2'-azo-bis(2-amidinopropane)]. DOX reduced
      Mb(IV) and inhibited lipid peroxidation also when H(2)O(2), Mb(III) and
      arachidonic acid were reacted in cytosol of human myocardial biopsies, a model
      developed to predict the cardiotoxic mode of action of DOX in patients. These
      results illustrate "antioxidant" properties of DOX, mediated by reduction of
      Mb(IV) to Mb(III), and cast doubts on lipid peroxidation as a causative mechanism
      of anthracycline-induced cardiotoxicity.

PMID- 12230413
TI  - Bioactivation of benzylamine to reactive intermediates in rodents: formation of
      glutathione, glutamate, and peptide conjugates.
AB  - The in vivo and in vitro disposition of benzylamine was investigated in rats.
      Benzylamine was metabolized to only a small extent by rat liver subcellular
      fractions. In contrast, it was extensively metabolized in vivo in rats. In vivo
      studies performed with stable isotope-labeled benzylamine enabled rapid mass
      spectrometric identification of metabolites present in rat bile and urine. The
      major metabolite of benzylamine was the hippuric acid formed by glycine
      conjugation of benzoic acid. LC/MS analysis of bile and urine obtained from rats
      dosed with 1:1 equimolar mixture of either d(0):d(7)- or d(0):d(2)-benzylamine
      showed the presence of several glutathione adducts in addition to the hippuric
      acid metabolite. The presence of various glutathione adducts indicated that
      benzylamine was metabolized to a number of reactive intermediates. Various
      metabolic pathways, including those independent of P450, were found to produce
      these intermediates. A previously undocumented pathway included the formation of
      a new carbon-nitrogen bond that led to a potentially reactive intermediate, Ar
      CH(2)-NH(CO)-X, capable of interacting with various nucleophiles. The origin of
      this reactive intermediate is postulated to occur via the formation of either a
      formamide or carbamic acid metabolites. Metabolites which were produced by the
      reaction of this intermediate, Ar-CH(2)-NH(CO)-X with nucleophiles included S
      [benzylcarbamoyl] glutathione, N-acetyl-S-[benzylcarbamoyl]cysteine, S
      [benzylcarbamoyl] cysteinylglycine, S-[benzylcarbamoyl] cysteinylglutamate, N
      [benzylcarbamoyl] glutamate, and an oxidized glutathione adduct. Bioactivation of
      amines via this pathway has not been previously described. The oxidative
      deamination of benzylamine yielding the benzaldehyde was demonstrated to be a
      precursor to the hippuric acid metabolite and S-benzyl-L-glutathione. The
      formation of the S-benzyl-L-glutathione conjugate showed that a net displacement
      of amine from benzylamine had taken place with a subsequent addition of
      glutathione at the benzylic position. In addition to these novel pathways, a
      number of other glutathione-derived adducts formed as a result of epoxide
      formation was characterized. It was demonstrated that benzylamine was converted
      by rat P450 2A1 and 2E1 to benzamide that was rapidly metabolized to an epoxide.
      Mechanisms are proposed for the formation of various GSH adducts of benzylamine.

PMID- 12230414
TI  - Pulmonary hypertension: hemodynamic diagnosis and management.
AB  - Hemodynamic classification of pulmonary hypertension relates to the hemodynamic
      mechanisms of pulmonary arterial hypertension, such as abnormalities of pulmonary
      blood flow, pulmonary vascular resistance, and pulmonary venous pressures. The
      therapeutic approaches can be directed to the hemodynamic mechanisms of pulmonary
      hypertension.

PMID- 12230415
TI  - The role of hormone replacement therapy in the prevention of Alzheimer disease.
AB  - Alzheimer disease (AD) is the most common form of dementia among the elderly. A
      higher prevalence of AD in women than in men suggests a link between gonadal
      hormone levels and AD. Increasing evidence supports a role for estrogen in brain
      regions involved in learning and memory and in the protection and regulation of
      cholinergic neurons, which degenerate in AD. Despite the lack of consensus, many
      studies indicate that hormone replacement therapy may decrease the risk for or
      delay the onset of AD in postmenopausal women. Recent trials have suggested that
      estrogen treatment may have no significant effect on the clinical course of AD in
      elderly women with the disease. Thus, the role of estrogen therapy seems to be
      confined to primary rather than secondary prevention of AD. Ongoing clinical
      studies may help to determine the role of estrogen in the cognitive function of
      postmenopausal women and in the prevention of AD.

PMID- 12230416
TI  - Cat-associated zoonoses.
AB  - Cats co-occupy one third of all residences in the United States. As common
      household pets, they serve as sources of joy and companionship for their owners.
      However, feline ownership also comes with its own inherent risks, as cats can
      transmit an array of diseases to their owners, ranging from trivial to fatal
      ailments. By understanding the pathogenesis of cat-associated diseases, owners
      and their pets can live together with little risk of disease transmission. This
      article reviews cat-related diseases, with an emphasis on their prevention and
      management.

PMID- 12230417
TI  - Hormone replacement therapy and associated risk of stroke in postmenopausal
      women.
AB  - BACKGROUND: There is little information about the risk of stroke in relation to
      time since initiation of hormone therapy and in relation to estrogen dose.
      METHODS: We conducted a population-based case-control study at Group Health
      Cooperative (GHC), a health maintenance organization in the greater Seattle
      (Wash) area, to assess the association of hormone replacement therapy with the
      risks of incident ischemic and hemorrhagic stroke. Cases were all postmenopausal
      women with incident stroke at GHC during July 1989 through December 1998 (726
      ischemic strokes and 213 hemorrhagic strokes). Controls were randomly selected
      from GHC enrollees and frequency matched to cases on age and calendar year (n =
      2525). Hormone use was assessed from computerized pharmacy data. We reviewed the
      medical record to confirm eligibility and assess other risk factors. RESULTS:
      After risk factor adjustment, ischemic stroke was not associated with current use
      of estrogen with progestin (odds ratio [95% confidence interval]: 0.97 [0.69
      1.37]) or without (0.94 [0.72-1.23]) compared with never use. Similarly,
      hemorrhagic stroke was not associated with current use of estrogen with progestin
      (0.74 [0.43-1.28]) or without (1.06 [0.71-1.56]). However, the risks of ischemic
      stroke and hemorrhagic stroke were increased 2-fold during the first 6 months of
      hormone use (ischemic stroke: 2.16 [1.04-4.49], hemorrhagic stroke: 2.20 [0.83
      5.81]). Risk of ischemic stroke also increased with estrogen dose (P for trend
      =.03). CONCLUSION: The transitory increase in risks of ischemic stroke and
      hemorrhagic stroke associated with initiation of hormone replacement therapy
      merits further investigation.

PMID- 12230418
TI  - Pneumococcal vaccination: analysis of opportunities in an inner-city hospital.
AB  - BACKGROUND: Adult pneumococcal vaccination rates for persons at risk of
      developing pneumococcal disease remain below desired levels. Various sites within
      the hospital (inpatient medicine wards [IMWs], general medicine clinics [GMCs],
      and emergency departments [EDs]) have been suggested as venues for administering
      vaccination. The cost-effectiveness of such sites for delivery of pneumococcal
      vaccination is not known. OBJECTIVE: To compare the potential coverage of at-risk
      patients and cost of pneumococcal vaccination delivered in an ED, GMC, and IMWs.
      METHODS: We studied a retrospective cohort of 300 patients with pneumococcal
      bacteremia who had been hospitalized at Cook County Hospital, an inner-city
      Chicago public teaching hospital, from January 1994 through December 1998. We
      measured the presence of risk factors, as defined by the Centers for Disease
      Control and Prevention, for developing pneumococcal disease prior to index
      admission for bacteremia; patient use of ED, GMC, and IMWs from 4 weeks to 5
      years before index admission; size of target population for vaccination in each
      site; and cost benefit of a pneumococcal vaccination strategy at each site.
      RESULTS: In the 4 weeks to 5 years before index admission, risk factors were
      present in 209 patients; 182 (87.1%) of the 209 had been in the ED, 104 (49.7%)
      in an IMW, and 64 (30.6%) in a GMC. The ED showed the greatest potential vaccine
      coverage, at a cost savings in a best-case scenario; the IMWs showed the best
      cost-benefit ratio but would provide access to fewer at-risk patients; and a
      program in the GMC would reach the fewest at-risk patients, with a cost-benefit
      ratio similar to that of the ED. CONCLUSIONS: The ED in an inner-city hospital
      has the potential to vaccinate more patients at risk of pneumococcal bacteremia
      than a GMC or IMWs, and may do so at a cost savings. A prospective evaluation of
      such a strategy is warranted.

PMID- 12230419
TI  - Prolonged thromboprophylaxis with oral anticoagulants after total hip
      arthroplasty: a prospective controlled randomized study.
AB  - BACKGROUND: The optimal duration of thromboprophylaxis after major orthopedic
      surgery is controversial. Although oral anticoagulants are still widely used for
      the prevention of venous thromboembolism after hip replacement, to our knowledge
      no study has assessed the benefit of prolonging anticoagulation beyond the
      hospital stay. METHODS: Consecutive patients who had received warfarin sodium
      prophylaxis after total hip arthroplasty were randomized to stop taking the drug
      at the time of hospital discharge or to continue taking it for 4 more weeks. The
      rate of symptomatic and asymptomatic venous thromboembolic events (as shown by
      compression ultrasonography of the proximal-vein system) occurring during the
      study period was compared between the 2 groups. The study was prematurely
      terminated after the inclusion of the first 360 patients because a statistically
      significant and clinically relevant superiority of extended over short-term
      thromboprophylaxis was observed. RESULTS: Objectively confirmed venous
      thromboembolic complications were recorded in 10 patients: 9 (5.1%) in the group
      of 176 control patients, and 1 (0.5%) in the group of 184 patients who continued
      the warfarin treatment. The absolute difference in the incidence of events was
      4.57% (95% confidence interval [CI], 1.15-7.99). The relative risk of venous
      thromboembolism developing in control patients compared with patients assigned to
      extended thromboprophylaxis was 9.4 (95% CI, 1.2-73.5). The number needed to
      treat was 22. Major bleeding developed in 1 patient who was randomized to the
      extended prophylaxis group (0.5%; 95% CI, 0.02-3.0) compared with none in the
      control group. CONCLUSION: Extending prophylaxis with warfarin for a few more
      weeks beyond the hospital stay has the potential to considerably improve the
      outcome of patients who undergo hip arthroplasty.

PMID- 12230420
TI  - Risk of progression to AIDS and death in women infected with HIV-1 initiating
      highly active antiretroviral treatment at different stages of disease.
AB  - BACKGROUND: The optimal virologic and immunologic stage at which to initiate
      antiretroviral therapy in individuals infected with human immunodeficiency virus
      type 1 (HIV-1) is undefined. METHODS: Among 1054 HIV-1-infected women in a
      prospective cohort study, we determined the time from initiation of highly active
      antiretroviral treatment (HAART) to acquired immunodeficiency syndrome (AIDS) and
      death. RESULTS: Median follow-up was 3.4 years. Of 553 women without AIDS at
      HAART initiation, 62 (11%) developed AIDS. Compared with women with CD4(+) cell
      counts greater than 350/microL at HAART initiation, women with cell counts of 200
      to 350/microL and less than 200/microL had relative hazards (RHs) for progression
      to AIDS of 0.93 (95% confidence interval [CI], 0.46-1.86) and 2.48 (95% CI, 1.39
      4.42), respectively. Compared with those with HIV-1 RNA values less than 5000
      copies/mL, women with 5000 to 50,000 copies/mL and greater than 50,000 copies/mL
      had RHs of 1.39 (95% CI, 0.74-2.64) and 2.09 (95% CI, 1.09-3.99), respectively.
      Among women with AIDS at HAART initiation (n = 501), RHs of death were 1.97 (95%
      CI, 0.84-4.66) and 3.35 (95% CI, 1.59-7.08) with CD4(+) cell counts of 200 to
      350/microL and less than 200/microL, respectively, relative to those with greater
      than 350/microL, and 1.90 (95% CI, 0.84-4.30) and 3.70 (95% CI, 1.81-7.54) for
      those with HIV-1 RNA values of 5000 to 50,000 and greater than 50,000 copies/mL,
      respectively, relative to those with less than 5000 copies/mL. CONCLUSIONS:
      Progression to AIDS and death was predicted by pre-HAART values of less than
      200/microL for CD4(+) cells and greater than 50,000 HIV-1 RNA copies/mL,
      indicating that deferral of HAART until the CD4(+) cell count is between 350 and
      200/microL is a valid strategy in the clinical management of HIV-1 infection.

PMID- 12230421
TI  - Utility of captopril renal scans for detecting renal artery stenosis.
AB  - BACKGROUND: Captopril renal scanning (CRS) is commonly recommended as a
      noninvasive method for detecting renal artery stenosis (RAS), based on
      performance characteristics determined in research settings. Scant data are
      available, however, regarding the utility of CRS in clinical practice. METHODS:
      We evaluated the performance characteristics (sensitivity, specificity, and
      predictive values) of CRS in a consecutive series of 90 patients who underwent
      both CRS and renal arteriography within a 6-month period (January 1, 1991,
      through December 31, 1995) at a university hospital. RESULTS: Among 86 eligible
      patients (and 169 kidneys), the prevalence of RAS was 43%. The sensitivity of CRS
      was 74% (95% confidence interval [CI], 62%-83%); the specificity was 59% (95% CI,
      49%-69%); the positive predictive value was 58% (95% CI, 47%-68%); and the
      negative predictive value was 75% (95% CI, 64%-84%). Also, there was evidence of
      spectrum bias, because the sensitivity and specificity (as well as the positive
      and negative predictive values) were different for groups with and without
      vascular disease. CONCLUSIONS: The results of CRS were substantially worse in a
      clinical practice setting than previously reported in research settings, despite
      a similar prevalence of RAS. Captopril renal scanning should not be used as an
      initial screening test for diagnosing RAS, even among patients with high clinical
      likelihood of disease.

PMID- 12230422
TI  - Cancer survival among US whites and minorities: a SEER (Surveillance,
      Epidemiology, and End Results) Program population-based study.
AB  - BACKGROUND: Available cancer statistics pertain primarily to white and African
      American populations. This study describes racial or ethnic patterns of cancer
      specific survival and relative risks (RRs) of cancer death for all cancers
      combined and for cancers of the colon and rectum, lung and bronchus, prostate,
      and female breast for the 6 major US racial or ethnic groups. METHODS: Cancer
      specific survival rates were analyzed for more than 1.78 million patients who
      resided in the 9 SEER (Surveillance, Epidemiology, and End Results) Program
      geographic areas and were diagnosed between 1975 and 1997 as having an incident
      invasive cancer, by 6 racial or ethnic groups (non-Hispanic whites, Hispanic
      whites, African Americans, Asian Americans, Hawaiian natives, and American
      Indians and Alaskan natives). RESULTS: Survival rates improved between 1988 to
      1997 for virtually all racial or ethnic groups. However, racial or ethnic
      differences in RRs of cancer death persisted after controlling for age for all
      cancers combined and for age and stage for specific cancer sites (P<.01). African
      American, American Indian and Alaskan native, and Hawaiian native patients tended
      to have higher RRs of cancer death than the other groups. American Indians and
      Alaskan natives generally exhibited the highest RRs of cancer death, except for
      colorectal cancer in males. CONCLUSIONS: Survival rates in patients with cancer
      have improved in recent years, but racial or ethnic differences in survival rates
      and in RRs of cancer death persist. Additional studies are needed to clarify the
      socioeconomic, medical, biological, cultural, and other determinants of these
      findings.

PMID- 12230423
TI  - Thrombolysis for acute stroke in routine clinical practice.
AB  - BACKGROUND: Studies have demonstrated that thrombolytic therapy for acute stroke
      can be given safely and effectively in study settings with experienced
      clinicians, but the patient outcomes associated with thrombolytic therapy in
      routine clinical practice require investigation. OBJECTIVES: To compare outcomes
      among patients given intravenous thrombolysis in routine clinical practice with
      the results of the National Institute of Neurological Disorders and Stroke rt-PA
      Study (NINDS cohort) and to examine whether protocol deviations are associated
      with adverse events. METHODS: Retrospective cohort of community-based patients
      given thrombolysis for acute stroke from May 1, 1996, through December 31, 1998,
      in 16 Connecticut hospitals (Connecticut cohort). RESULTS: Forty-two (67%) of 63
      patients in the Connecticut cohort had at least 1 major protocol deviation, and
      61 (97%) had major or minor protocol deviations. Overall, the in-hospital
      mortality was higher in the Connecticut cohort (16/63 [25%]) compared with the
      NINDS cohort (40/312 [13%]; P =.01). The serious extracranial hemorrhage rate was
      also higher for the Connecticut cohort (8/63 [13%] vs 5/312 [2%]; P =.001).
      Patients in the Connecticut cohort without major protocol deviations had outcomes
      similar to those in the NINDS cohort; however, patients in the Connecticut cohort
      with major protocol deviations had higher rates of in-hospital mortality (13/42
      [31%] vs 40/312 [13%]; P =.002) and serious extracranial hemorrhage (7/42 [17%]
      vs 5/312 [2%]; P =.001). CONCLUSIONS: Protocol deviations occur commonly when
      thrombolytic therapy is given to stroke patients in routine clinical practice.
      Patients who receive thrombolysis with major protocol deviations have higher
      rates of in-hospital mortality and serious extracranial hemorrhage than patients
      in the NINDS cohort.

PMID- 12230424
TI  - Nephrologist care and mortality in patients with chronic renal insufficiency.
AB  - BACKGROUND: For patients with chronic renal insufficiency, rates of referral to
      nephrologists are highly variable, and little is known about the effect of such
      consultation on clinical outcomes. We sought to determine whether early or
      frequent access to nephrologist care prior to the initiation of dialysis was
      associated with a difference in mortality rates in the first year after dialysis
      began. METHODS: We identified all patients in the New Jersey Medicaid and
      Medicare programs who began maintenance dialysis during a 6-year period and who
      had been diagnosed with renal disease more than 12 months prior to dialysis. Use
      of nephrologist services was documented during this 1-year period, along with
      other clinical and sociodemographic variables. The outcome measure of our
      analysis was mortality in the first year after initiation of dialysis. RESULTS:
      From multivariate analyses, we found that patients who did not see a nephrologist
      until 90 days or less before initiation of dialysis had a 37% higher likelihood
      of death in the first year of dialysis compared with patients with earlier
      referral (95% confidence interval, 1.22-1.52; P<.001). Similarly, those who saw a
      nephrologist on fewer than 5 occasions in the year prior to dialysis had a 15%
      higher mortality rate in the first year of dialysis compared with those who had
      had 5 or more nephrologist visits (95% confidence interval, 1.03-1.28; P =.01).
      CONCLUSIONS: For patients with long-standing renal disease, earlier consultation
      with a nephrologist and more frequent specialist encounters is associated with
      lower mortality in the first year of dialysis. These findings need to be
      confirmed in younger and less indigent patients as well.

PMID- 12230425
TI  - Bilateral external laryngoceles following radioiodine ablation for Graves
      disease.
AB  - A 28-year-old trumpet player underwent multiple treatments with radioactive
      iodine for Graves disease associated with an unusually large goiter. Following
      his second treatment, the patient developed acute neck pain and swelling.
      Radiographic studies and a laryngoscopy demonstrated bilateral symptomatic
      external laryngoceles, a very rare entity, not previously known to be associated
      with radioiodine treatment or Graves disease. The patient's profession placed him
      at risk for the development of a laryngocele, but the temporal relationship to
      goiter regression following radioiodine therapy suggests that this occurred as a
      result of this treatment. The patient's disease was managed nonsurgically, and he
      has subsequently done well. This represents the first known association of
      symptomatic laryngocele with radioiodine treatment for Graves disease.

PMID- 12230426
TI  - Concurrent use of selected agents with moxifloxacin: an examination of labeling
      compliance within 1 year of marketing.

PMID- 12230427
TI  - Male-specific suppression of hepatic microsomal UDP-glucuronosyl transferase
      activities toward sex hormones in the adult male rat administered bisphenol A.
AB  - Various adverse effects of endocrine disruptors on the reproductive organs of
      male animals have been reported. We found that UDP-glucuronosyltransferase (UGT)
      activities towards bisphenol A, testosterone and oestradiol were significantly
      decreased in liver microsomes prepared from adult male Wistar rats administered
      with the endocrine disruptor bisphenol A (1 mg/2 days for 2 or 4 weeks). However,
      suppression of the transferase activities was not observed in female rats, even
      after bisphenol A treatment for 4 weeks. Diethylstilbestrol, which is well known
      as an endocrine disruptor, had the same effects, but p -cumylphenol had no effect
      on UGT activities towards sex hormones. Co-administration of an anti-oestrogen,
      tamoxifen, inhibited the suppression of the transferase activities by bisphenol
      A. Western blotting analysis showed that the amount of UGT2B1, an isoform of UGT
      which glucuronidates bisphenol A, was decreased in the rat liver microsomes by
      the treatment. Northern blotting analysis also indicated that UGT2B1 mRNA in the
      liver was decreased by bisphenol A treatment. The suppression of UGT activities,
      UGT2B1 protein and UGT2B1 mRNA expression did not occur in female rats. The
      results indicate that bisphenol A treatment reduces the mRNA expression of UGT2B1
      and other UGT isoforms that mediate the glucuronidation of sex hormones in adult
      male rats, and this suggests that the endocrine balance may be disrupted by
      suppression of glucuronidation.

PMID- 12230430
TI  - Staff perceptions of care for deliberate self-harm patients in rural Western
      Australia: a qualitative study.
AB  - Suicide has been a major community concern in Esperance, a geographically
      isolated port on the south coast of Western Australia. This study explores the
      views of regional health staff on barriers to the effective management of
      deliberate self-harm (DSH) and ways in which those barriers could be addressed.
      Semi-structured interviews were tape-recorded, transcribed and subjected to
      qualitative content analysis. Interviewees included 77% of general practitioners
      (n = 7), 18% of nurses (n = 13) and 55% of mental health professionals (n = 5).
      The most important barrier was a lack of structure to treating DSH, resulting in
      deficiencies and inconsistencies in its management. Suggestions to improve the
      management of DSH included better communication between services, support for
      nurses in raising the issue of suicide, use of a simple risk assessment tool, the
      development of a nurse liaison position, and a multidisciplinary planning group.
      The higher rates of DSH and completed suicide in rural and remote regions
      compared with metropolitan areas make secondary prevention particularly
      important.

PMID- 12230428
TI  - Overexpression of c-myc in diabetic mice restores altered expression of the
      transcription factor genes that regulate liver metabolism.
AB  - Overexpression of the c-Myc transcription factor in liver induces glucose uptake
      and utilization. Here we examined the effects of c- myc overexpression on the
      expression of hepatocyte-specific transcription factor genes which regulate the
      expression of genes controlling hepatic metabolism. At 4 months after
      streptozotocin (STZ) treatment, most diabetic control mice were highly
      hyperglycaemic and died, whereas in STZ-treated transgenic mice hyperglycaemia
      was markedly lower, the serum levels of beta-hydroxybutyrate, triacylglycerols
      and non-esterified fatty acids were normal, and they had greater viability in the
      absence of insulin. Furthermore, long-term STZ-treated transgenic mice showed
      similar glucose utilization and storage to healthy controls. This was consistent
      with the expression of glycolytic genes becoming normalized. In addition,
      restoration of gene expression of the transcription factor, sterol receptor
      element binding protein 1c, was observed in the livers of these transgenic mice.
      Further, in STZ-treated transgenic mice the expression of genes involved in the
      control of gluconeogenesis (phosphoenolpyruvate carbokykinase), ketogenesis (3
      hydroxy-3-methylglutaryl-CoA synthase) and energy metabolism (uncoupling protein
      2) had returned to normal. These findings were correlated with decreased
      expression of genes encoding the transcription factors hepatocyte nuclear factor
      3gamma, peroxisome proliferator-activated receptor alpha and retinoid X receptor.
      These results indicate that c- myc overexpression may counteract diabetic changes
      by controlling hepatic glucose metabolism, both directly by altering the
      expression of metabolic genes and through the expression of key transcription
      factor genes.

PMID- 12230429
TI  - Basic fibroblast growth factor as a selective inducer of matrix Gla protein gene
      expression in proliferative chondrocytes.
AB  - Matrix Gla protein (MGP) is a member of the vitamin K-dependent gamma carboxylase
      protein family expressed in cartilage. Insulin-like growth factor I (IGF1)
      stimulates chondrocyte differentiation, whereas basic fibroblast growth factor
      (FGF2) acts in an opposite manner. We explored the differential expression and
      regulation by IGF1 and FGF2 of the MGP gene during chondrocyte differentiation.
      We used a primary culture system of rabbit epiphyseal chondrocytes to show that
      MGP mRNA is mainly expressed during serum-induced proliferation. Much lower MGP
      mRNA content is observed in post-mitotic chondrocytes, which newly express alpha
      1X procollagen mRNA, a marker of late-differentiated cells. From studies of a
      series of growth factors, it was shown that IGF1 decreased chondrocyte MGP
      transcripts, whereas FGF2 had the opposite effect. FGF2 stimulated chondrocyte
      MGP production in a dose- and time-dependent manner at the mRNA and protein
      levels. FGF2 acted in a dose- and time-dependent manner, reaching a maximum at 10
      ng/ml at 20 h. The protein synthesis inhibitor cycloheximide did not modify FGF2
      action, in agreement with a direct effect. Actinomycin D abolished FGF2-induced
      stimulation, strongly suggesting that FGF2 modulated MGP gene transcription. We
      transiently transfected chondrocytes with a construct containing the mouse MGP
      promoter from -5000 to -168 base pairs, relative to the transcription start site
      of the gene linked to the luciferase gene (MGP-Luc). In transfected cells, FGF2
      stimulated luciferase activity up to sevenfold while IGF1 had no effect. Hence,
      FGF2 induces transcription of the MGP gene via the 5'-flanking region of the
      gene. Using a series of deleted MGP-Luc constructs, we identified a sequence of
      748 base pairs which was sufficient for transcriptional activation by FGF2. These
      results led us to postulate that the inhibitory chondrogenic action of FGF2
      involves a mechanism whereby MGP gene transcription and protein are induced.

PMID- 12230431
TI  - Undergraduate nursing students' clinical experiences in rural and remote areas:
      recruitment implications.
AB  - Providing rural and remote clinical experiences for undergraduate nursing
      students could help address future recruitment in these areas, but adequate
      financial support for students during clinical placements is also necessary.
      Strategies to address nursing shortages to date have emphasised funding for rural
      re-entry programs, or supporting students from rural backgrounds to attend
      university courses. Assisting current undergraduate nursing students, especially
      those from urban backgrounds, to experience living and working in rural areas has
      been overlooked as a potential recruitment strategy. Ongoing qualitative
      evaluation of a clinical placement program shows students respond positively and
      with increased interest in returning to rural nursing after graduation.
      Unfortunately, many are disadvantaged financially by the added expense of their
      rural clinical rotation. Finding ways to support students from both urban and non
      urban backgrounds to undertake rural and remote clinical placements should be an
      important strategic and funding priority.

PMID- 12230432
TI  - Management of HIV/AIDS on the Mid North Coast: a collaborative model of care
      involving general practitioners and the public health system.
AB  - The Coffs Harbour AIDS Information Network was set up to co-ordinate care
      planning and support service delivery for HIV/AIDS patients. This paper describes
      a collaborative model of care that brought together private general
      practitioners, a community nurse and a sexual health counsellor. Time involved in
      delivering services was monitored for each of the health professional groups
      during a 6 month period. Twenty-three patients were involved in our study.
      Doctors averaged 23 min per consultation over 57 occasions of service. Travel or
      telephone contact took up 17% of the time spent on these patients. Corresponding
      figures for the nurse and counsellor were an average of 67 min over 144 services
      and 71 min over 16 services. They spent 16% and 27% of their time travelling or
      on the phone, respectively. HIV/AIDS care is time consuming for health
      professionals but comprehensive care can be given in rural areas with adequate
      support and integration.

PMID- 12230433
TI  - Management of episodes of incapacity by families in rural and remote Queensland.
AB  - People in rural and remote areas have relatively poor health, so limited
      availability of and accessibility to doctors are major health issues. This cross
      sectional study was conducted in rural and remote areas of Central Queensland.
      Using telephone interviews, the study described the use of formal and informal
      health services by families in response to episodes of incapacity. An episode of
      incapacity was defined as inability to conduct ordinary activities for at least
      half a day due to new or continued illness. Of the 394 households contacted, 270
      (68.5%) provided information about 698 household members, of whom 269 (38.5%)
      reported at least one episode of incapacity in the previous 12 months. The
      respondents could report more than one type of management of an illness episode.
      The management of the most recent episode in each member included 68% visiting
      doctors and 8.2% using services at an accident and emergency unit. Persons living
      in "least" medically resourced areas were more likely than persons in relatively
      "high" and "moderate" areas to consult doctors, but were also more likely to
      first consult books and delay their visits. They also consulted by telephone
      three times more frequently. Only 7% consulted other health practitioners
      including nurses and chemists, suggesting that these health practitioners were
      not used by families in rural and remote areas during episodes of incapacity.
      Increasing the availability and accessibility of medical care resources in rural
      and remote areas, using alternative delivery methods such as telemedicine, may
      meet the health needs of rural populations.

PMID- 12230434
TI  - Goal attainment scaling: an effective outcome measure for rural and remote health
      services.
AB  - The aim of this paper is to demonstrate the utility of Goal Attainment Scaling
      (GAS) as an effective, multidisciplinary measure of client outcomes for rural and
      remote health services. Goal Attainment Scaling was adopted by the Spinal
      Outreach Team (SPOT) as a client-focussed evaluation tool, as it is sensitive to
      the individual nature of clients' presenting issues and the multidisciplinary
      focus of the team. It enables individualised goals to be set on a five-point
      scale. Goal Attainment Scaling was introduced to the SPOT service after a pilot
      trial established guidelines for its effective implementation. An ongoing review
      process ensures that goal scaling remains realistic and relevant. Service
      outcomes can be effectively summarised using a frequency distribution of GAS
      scores. One of the important benefits of GAS is its facilitation of collaborative
      goal setting between clinician and client. Goal Attainment Scaling is recommended
      to rural and remote multidisciplinary health services because of its ability to
      summarise outcomes from heterogeneous service activities.

PMID- 12230436
TI  - Australian College of Rural and Remote Medicine.

PMID- 12230437
TI  - Reflections on the life and times of SARRAH.

PMID- 12230438
TI  - Is paternalism alive and well in obstetric ultrasound? Helping couples choose
      their children.

PMID- 12230440
TI  - Prenatal ultrasonographic diagnosis of talipes equinovarus: does it give the full
      picture?

PMID- 12230441
TI  - One-stop clinic for assessment of risk for trisomy 21 at 11-14 weeks: a
      prospective study of 15 030 pregnancies.
AB  - OBJECTIVE: To evaluate the performance of a one-stop clinic for assessment of
      risk (OSCAR) for trisomy 21 by a combination of maternal age, fetal nuchal
      translucency (NT) thickness and maternal serum free beta-human chorionic
      gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14
      weeks of gestation. METHOD: Screening for trisomy 21 was carried out by OSCAR in
      15 030 singleton pregnancies with live fetuses at 11-14 weeks. The estimated risk
      for trisomy 21 was calculated, and the women were counseled regarding this risk
      and the option of invasive testing or expectant management. Follow-up of the
      outcome of all pregnancies was carried out. The detection and false-positive
      rates for different risk cut-offs were calculated. RESULTS: Fetal NT and maternal
      serum free beta-hCG and PAPP-A were successfully measured in all cases. Pregnancy
      outcome, including karyotype results or the birth of a phenotypically normal
      baby, was obtained from 14 383 cases. The median maternal age of these cases was
      34 (range 15-49) years and in 6768 (47.1%) the age was 35 years or greater. The
      median gestation at screening was 12 (range 11-14) weeks and the median fetal
      crown-rump length was 64 (range 45-84) mm. The estimated risk for trisomy 21
      based on maternal age, fetal NT and maternal serum free beta-hCG and PAPP-A was 1
      in 300 or greater in 6.8% (967 of 14 240) normal pregnancies, in 91.5% (75 of 82)
      of those with trisomy 21 and in 88.5% (54 of 61) of those with other chromosomal
      defects. For a fixed false-positive rate of 5% the respective detection rates of
      screening for trisomy 21 by maternal age alone, maternal age and serum free beta
      hCG and PAPP-A, maternal age and fetal NT, and by maternal age, fetal NT and
      maternal serum biochemistry were 30.5%, 59.8%, 79.3% and 90.2%, respectively.
      CONCLUSION: Screening for trisomy 21 by a combination of maternal age, fetal NT
      and maternal serum biochemistry at 11-14 weeks can be provided in an OSCAR
      setting and is associated with a detection rate of about 90% for a false-positive
      rate of 5%.

PMID- 12230442
TI  - Outcome of antenatally diagnosed talipes equinovarus in an unselected obstetric
      population.
AB  - OBJECTIVE: To investigate the natural history and outcome of fetal talipes
      diagnosed by routine ultrasound scanning at 18-23 weeks' gestation. PATIENTS AND
      METHODS: This was a retrospective study of 103 228 pregnancies undergoing routine
      ultrasound scanning at 18-23 weeks' gestation. A computer search was made to
      identify all cases of fetal talipes and the records of these patients were
      examined to determine the incidence of other defects and pregnancy outcome.
      RESULTS: The incidence of fetal talipes following routine ultrasound examination
      was 0.10% (107/103 228) and was bilateral in 64 (59.8%) and unilateral in 43
      (40.2%) cases. In 52 (48.6%) cases, talipes was of complex etiology, as it was
      associated with other defects, while, in 55 (51.4%) cases, it was classified as
      idiopathic. In 19% of cases, an initial diagnosis of idiopathic talipes was
      changed to complex, because of the subsequent development of associated features.
      Perinatal death and long-term neurodevelopmental or musculoskeletal problems were
      significantly more common when the talipes was complex rather than idiopathic
      (odds ratio, 150; 95% confidence interval, 34-665). Adverse outcomes were also
      seen more frequently with bilateral compared to unilateral talipes (odds ratio,
      3.44; 95% confidence interval, 1.50-7.90). CONCLUSION: The outcome of antenatally
      detected talipes is mainly dependent on the presence or absence of other defects.
      A significant proportion of cases, thought to be idiopathic at presentation, will
      develop associated complex features when reassessed on subsequent scans or
      postnatally.

PMID- 12230443
TI  - Comparison of feticide carried out by cordocentesis versus cardiac puncture.
AB  - OBJECTIVE: Feticide may be achieved by the injection of strong potassium chloride
      (KCl) into the fetal circulation via the cardiac route, or less frequently, into
      the umbilical cord. Despite the relative frequency of this procedure, little
      published information is available on the subject. SUBJECTS AND METHODS: This was
      a retrospective analysis of all feticide procedures carried out prior to legal
      pregnancy termination in mid trimester of pregnancy from January 1996 to July
      2001, in a tertiary fetal medicine referral center. The effect of gestational age
      and the route of access to fetal the circulation on the dose of strong KCl
      required to achieve cardiac asystole was evaluated. RESULTS: A total of 106 women
      underwent the procedure of feticide during the study period. Gestational age had
      no effect on the dose of strong KCl. The median dose of KCl administered by
      cordocentesis (5 mL) was significantly less (P < 0.001) than the dose required
      when fetal cardiocentesis was performed for administration of the drug (10 mL).
      CONCLUSION: This is the first comparative study of feticide by the administration
      of strong KCl by fetal cardiocentesis and cordocentesis. The study demonstrates
      that both cardiac and umbilical routes can be used to achieve feticide
      effectively, without compromising maternal safety. A finding of this study is
      that significantly smaller doses of KCl were required to achieve fetal cardiac
      asystole when using the umbilical compared to the cardiac route, although this
      may be explained by differences in technique. Strong 15% KCl can safely be used
      to achieve feticide in volumes up to 20 mL for cardiocentesis and 8 mL for
      cordocentesis.

PMID- 12230444
TI  - Venous Doppler velocimetry in the surveillance of severely compromised fetuses.
AB  - OBJECTIVE: To investigate whether venous Doppler velocimetric signs of cardiac
      decompensation might predict fetal demise in severely compromised fetuses.
      MATERIAL AND METHODS: This was a prospective study involving 154 growth
      restricted fetuses, 37 of which were found to have reversed flow in the umbilical
      artery (BFC III). Doppler velocimetry of the right hepatic vein and ductus
      venosus were investigated serially and the presence of umbilical venous
      pulsations also registered. Only the final examination prior to birth or fetal
      demise was accepted for analysis and related to obstetric outcome defined as
      gestational age at birth, birth weight and perinatal mortality. In cases of BFC
      III the venous velocimetry of 15 nonsurviving fetuses was compared to that of the
      22 survivors. RESULTS: There was a significant correlation between venous blood
      velocity and placental vascular resistance. In the right hepatic vein there was a
      significant decrease in peak systolic and end-systolic velocities and an increase
      of maximum velocity during atrial contraction and pulsatility (P < 0.05). A
      decrease of all velocities and increase of pulsatility were noted in the ductus
      venosus (P < 0.05). A reversed flow in the ductus venosus was found in 9/37
      fetuses and double umbilical venous pulsations in 16/37 fetuses. However, the
      hepatic vein seemed to be a better predictor of impending mortality than the
      ductus venosus. Changes in diastolic venous blood velocity and a double pulsation
      in the umbilical vein were closely related to perinatal mortality, although these
      parameters did not provide a useful threshold to optimize the timing of delivery.
      CONCLUSION: Diastolic venous velocimetry changes significantly in severely
      compromised fetuses. These changes might be of great clinical value in deciding
      on the timing of delivery to minimize damage to the fetus and newborn.

PMID- 12230445
TI  - Changes in fetoplacental vessel flow velocity waveforms following maternal
      administration of betamethasone.
AB  - OBJECTIVE: To determine the timing of the onset of the umbilical artery flow
      velocity waveform changes following maternal administration of betamethasone in
      pregnancies complicated by umbilical artery absent end-diastolic flow, and to
      explore whether these changes are associated with flow velocity waveform changes
      in other fetoplacental vessels. SUBJECTS AND METHODS: This was a prospective
      study of 12 women with pregnancies complicated by umbilical artery absent end
      diastolic flow. Flow velocity waveforms were recorded from the umbilical artery,
      fetal middle cerebral artery, renal artery, aorta and ductus venosus, before and
      after maternal betamethasone administration, using real-time pulsed wave Doppler.
      RESULTS: In all 12 pregnancies, the administration of maternal betamethasone was
      followed by the return of end-diastolic flow within 24 h. End-diastolic flow was
      first observed at 4 h and was present in all women studied at 8 h. In addition,
      there was a statistically significant decrease in the pulsatility index in the
      fetal aorta at 8 h and the middle cerebral artery at 24 h. No change was observed
      in the ductus venosus or the renal artery flow velocity waveforms. CONCLUSION:
      The findings suggest that, in pregnancies complicated by absent end-diastolic
      flow in the umbilical artery, maternally administered betamethasone induces a
      return in umbilical artery end-diastolic flow as early as 4 h, along with
      widespread vasodilatation throughout the fetoplacental vasculature.

PMID- 12230446
TI  - Prediction of preterm premature rupture of membranes by transvaginal ultrasound
      features and risk factors in a high-risk population.
AB  - OBJECTIVE: To determine the transvaginal ultrasound features and risk factors
      that predict preterm delivery (PTD) preceded by either preterm premature rupture
      of membranes (PPROM) or preterm labor (PTL) in a high-risk population. STUDY
      DESIGN: Singleton gestations at high-risk for preterm delivery were screened
      prospectively with transvaginal ultrasound between 14 and 24 weeks. Univariate
      and multivariate regression analyses were performed for historical obstetric risk
      factors and transvaginal ultrasound features (cervical length (CL) and cervical
      funneling (CF)) for the prediction of PTD preceded by PPROM or PTL at < 32 and <
      35 weeks' gestation, respectively. Indicated preterm deliveries were excluded.
      RESULTS: Of 321 patients screened, 71 (22%) delivered at < 35 weeks, 40 (56%)
      after PPROM and 31 (44%) after PTL. Preterm delivery at < 32 weeks was seen in 47
      patients (15%), with 20 (43%) occurring after PTL and 27 (57%) after PPROM.
      Univariate analysis showed the following to be significant predictors of PPROM at
      < 35 weeks: a past history of PTD between 25 and 30 weeks (P < 0.008), cerclage
      in the current pregnancy (P < 0.0001), bacterial vaginosis (P < 0.011), CL < 25
      mm (P < 0.0001) and CF > 25% (P < 0.0001). The following were found to be
      significant predictors of PTL at < 35 weeks: black race (P < 0.02), a cerclage in
      the current pregnancy (P < 0.01), CL < 25 mm (P < 0.001) and CF > 25% (P <
      0.0001). The significant predictors of PPROM at < 32 weeks were cerclage in the
      current pregnancy (P < 0.006) and CL < 25 mm (P < 0.0001); for PTL at < 32 weeks
      they were a past history of spontaneous miscarriage between 14 and 24 weeks (P <
      0.02), black race (P < 0.021), cerclage in the current pregnancy (P < 0.001) and
      CL < 25 mm (P < 0.001). Multivariate regression analysis revealed the significant
      predictors of PPROM at < 35 weeks to be: a history of PTD between 25 and 30 weeks
      with odds ratio (OR) 4.8 (95% confidence interval (CI), 1.9-11.5) and CL < 25 mm
      with OR 7.9 (95% CI, 3.6-17.5). The significant predictors of PTL at < 35 weeks
      on multivariate regression were black race with OR 2.2 (95% CI, 1.0-4.8) and
      unemployment with OR 1.2 (95% CI, 1.0-1.5). For deliveries < 32 weeks, CL < 25 mm
      (OR, 10.1; 95% CI, 3.2-32) was the only significant predictor of PPROM.
      Significant predictors of PTL were unemployment (OR, 1.3; 95% CI, 1.1-1.7), a
      history of spontaneous miscarriage between 14 and 24 weeks (OR, 6.2; 95% CI, 1.4
      25), black race (OR, 8.6; 95% CI, 1.5-47) and CL < 25 mm (OR, 4.4; 95% CI, 1-19).
      The sensitivity, specificity and positive and negative predictive values of CL <
      25 mm for PPROM at < 35 weeks were 73%, 69%, 25% and 95%, respectively; for PTL
      at < 35 weeks they were 58%, 66%, 15% and 94%; for PPROM at < 32 weeks they were
      85%, 68%, 20%, and 98%; for PTL at < 32 weeks they were 70%, 66%, 12% and 97%.
      CONCLUSION: There are differences in both transvaginal ultrasound findings and
      risk factors that predict PPROM or PTL. Of the pathways leading to PTD, CL was a
      more significant predictor of PPROM compared with PTL, while sociodemographic
      factors were more predictive of PTL.

PMID- 12230447
TI  - Funneling to the stitch: an informative ultrasonographic finding after cervical
      cerclage.
AB  - OBJECTIVE: The purpose of this study was to evaluate the utility of ultrasound
      surveillance after cerclage placement and to propose a rationale for cervical
      sonography in this setting. SUBJECTS AND METHODS: This was a retrospective
      analysis of 53 women undergoing cervical cerclage by a maternal-fetal medicine
      specialist, regardless of indication, and delivering between January 1999 and
      April 2001. Transvaginal ultrasonographic assessment of cervical length and the
      degree of cervical funneling after cerclage were compared to preoperative values
      and to outcomes including gestational age at delivery. Funneling to the cerclage
      was defined as membranes prolapsing down the endocervical canal until they
      reached the plane of the cerclage. RESULTS: Cervical cerclage resulted in a
      significant increase in cervical length from 2.1 +/- 1.2 cm to 2.9 +/- 0.8 cm
      after the procedure, P < 0.001; however, this measure was not correlated with
      gestational age at delivery. Funneling to the level of the cerclage was
      associated with an earlier gestational age at delivery 31.3 +/- 5.6 weeks vs.
      36.8 +/- 2.8 weeks for those cases without this finding, P < 0.001. A
      statistically significant association between funneling to the cerclage and
      preterm delivery was identified irrespective of the indication (prophylactic or
      emergency) for the procedure. When descent of the membranes to the level of the
      cerclage was noted, it occurred by 28 weeks' gestation in all patients studied.
      The incidence of premature rupture of the membranes was also significantly
      greater postcerclage in women with descent of the membranes to the cerclage (52%)
      compared to those without this finding (9%) P= 0.002. CONCLUSIONS: Funneling to
      the cerclage is significantly associated with earlier preterm delivery in
      patients who have undergone cervical cerclage. Serial sonography up to 28 weeks'
      gestation is useful in identifying patients at higher risk for premature rupture
      of the membranes and preterm delivery.

PMID- 12230448
TI  - Intra- and interobserver reproducibility of ultrasound measurements of cervical
      length and width in the second and third trimesters of pregnancy.
AB  - OBJECTIVES: To determine intra- and interobserver reproducibility of ultrasound
      measurements of cervical length and width in the second and third trimesters of
      pregnancy. DESIGN: Twenty healthy women in the second or third trimester of
      pregnancy underwent transvaginal ultrasound examination of the cervix by two
      examiners. Three replicate meaurements of cervical length and width were taken by
      each observer for each woman. Intraobserver repeatability was expressed as the
      difference between the highest and lowest measurement value obtained by one
      observer, and as the repeatability coefficient and intraclass correlation
      coefficient. Interobserver reproducibility was expressed as the difference
      between the mean of the three measurements of each observer, limits of agreement,
      and interclass correlation coefficient. The repeatability coefficient/limits of
      agreement define the range within which 95% of the differences between two
      measurements by the same observer/two observers are likely to fall. RESULTS:
      Intra- and interobserver differences did not vary in any systematic way over the
      range of values measured. For cervical length measurements the repeatability
      coefficient was +/- 5.4 mm for Observer 1 and +/- 5.9 mm for Observer 2. The
      intraclass correlation coefficient for cervical length measurements was 0.93 for
      both observers. The corresponding coefficients for cervical width measurements
      were +/- 3.9 mm and +/- 7.3 mm, and 0.97 and 0.91. The interclass correlation
      coefficient for cervical length measurements was 0.76, the mean interobserver
      difference was 0.4 mm, and the limits of agreement were -10.0 mm to 10.8 mm. For
      cervical width measurements the interclass correlation coefficient was 0.74, the
      mean interobserver difference was -0.02 mm, and the limits of agreement were 
      12.4 mm to 12.4 mm. There was no systematic difference between the first, second
      and third cervical length measurements and no systematic bias between the two
      observers, and the results were not affected by which of the two examiners
      started the examination (three-way analysis of variance). The same was true of
      cervical width measurements. CONCLUSIONS: Our results do not support the
      contention that the first measurement of cervical length is the longest. There is
      substantial intra- and interobserver variability in the results of measurements
      of cervical length and width, even when experienced observers perform the
      measurements under standardized conditions. It is important to consider the
      possibility of 'measurement error' when ultrasound measurements of cervical
      length and width are used in clinical practice to monitor women at high risk of
      delivering preterm or to screen for preterm birth.

PMID- 12230449
TI  - Effect of maternal position on cervical length measurement in twin pregnancies.
AB  - OBJECTIVE: To compare cervical length measurements in twin pregnancies obtained
      from patients in the recumbent and standing positions. METHODS: Fifty women with
      uncomplicated twin pregnancies underwent monthly transvaginal ultrasound
      examinations for cervical length measurement in the recumbent and standing
      positions. The correlation between cervical length measurements obtained in the
      recumbent and standing positions, and between these measurements and gestational
      age, were examined. The significance of the differences between measurements
      obtained in the recumbent and standing positions was also analyzed. RESULTS:
      Based on data obtained at the first ultrasound examination, there was a
      significant correlation between cervical length measurements in the recumbent and
      standing positions (r = 0.77; t = 8.25; P < 0.0001) and both measurements showed
      a significant inverse correlation with gestational age (recumbent position: r = 
      0.60, P < 0.0001; standing position: r = -0.46; P = 0.0008). The mean of the
      differences (standing - recumbent) was -1.8 mm (95% confidence interval = -3.7
      0.04; t = -1.96; P = 0.06) and the mean of percentage differences ((standing -
      recumbent)/recumbent x 100) was -2.9% (95% confidence interval = -8.6-2.7; t = 
      1.04; P = 0.3). When the data obtained at all examinations were examined by
      multiple regression analysis, cervical length measurement in the recumbent
      position was the only parameter that correlated significantly with the percentage
      difference between cervical length measurements (P < 0.0001). CONCLUSIONS:
      Cervical length in twin pregnancies decreases with gestation and there is a good
      correlation between measurements obtained from women in the recumbent and
      standing positions. No significant changes in cervical length were observed
      comparing measurements obtained in the two maternal positions.

PMID- 12230450
TI  - Gestational sac diameter in very early pregnancy as a predictor of fetal outcome.
AB  - OBJECTIVE: To determine whether transvaginal sonographic measurement of
      gestational sac diameter in pregnancies 28-42 days from the last menstrual period
      can predict whether a pregnancy results in a normal term birth or a spontaneous
      miscarriage. DESIGN: Gestational sac diameter was measured during the 4th and 5th
      weeks of gestation from the last menstrual period in 67 women who had a total of
      102 ultrasound scans. These pregnancies were followed until one of two outcomes
      occurred: term gestation (n = 32) or spontaneous miscarriage (n = 35).
      Gestational sac diameter as a function of gestational age was compared in each of
      the groups. RESULTS: The mean diameter of the gestational sac at 28-35 days from
      the last menstrual period among normal pregnancies did not differ significantly
      from that in those that subsequently miscarried (2.6 mm vs. 2.7 mm; P = 1.00). In
      pregnancies 36-42 days from the last menstrual period, the mean sac diameter was
      significantly different between the two groups (normal group, mean sac diameter,
      8.2 mm and miscarriage group, mean sac diameter, 4.5 mm; P < 0.001). CONCLUSION:
      There is no difference in gestational sac diameter at 28-35 days from the last
      menstrual period in normal and abnormal pregnancies. However, smaller than
      expected sac diameter in pregnancies 36-42 days from the last menstrual period is
      predictive of spontaneous miscarriage.

PMID- 12230451
TI  - Quantitative transvaginal two- and three-dimensional sonography of the ovaries:
      reproducibility of antral follicle counts.
AB  - OBJECTIVE: To assess the intra- and interobserver reproducibilities in addition
      to the between-method reliability of antral follicle counts using two (2D)- and
      three (3D)-dimensional transvaginal sonography (TVS). METHODS: Two groups of
      women with regular menstrual cycles were studied. One group consisted of healthy
      volunteers with proven fertility and the other group consisted of patients
      visiting the general infertility clinic. In each woman, 2D or 3D TVS was
      performed in the early follicular phase (day 2, 3 or 4) of the menstrual cycle to
      measure the number of antral follicles (2-10 mm). RESULTS: Intraobserver
      reproducibility was calculated from follicle counts using 3D TVS in 41 women. The
      intraclass correlation coefficient was 0.99 and the 95% coverage interval of the
      difference (CID) was -3.2 to +3.2. Interobserver reproducibility was assessed
      from both 2D (n = 37) and 3D (n = 49) TVS-based follicle counts. An interclass
      correlation coefficient of 0.98 was found for both methods. The 95% CID was -5.0
      to +4.1 for 2D and -5.6 to +5.7 for 3D measurements. The latter CID appeared to
      increase in the higher range of counts. Finally, the degree of agreement between
      2D and 3D TVS counts (n = 76) was characterized by a 95% CID of -5.3 to +8.3.
      This coverage interval widened when higher numbers of follicles were counted.
      With the exception of the between-method analysis, kappa values indicated overall
      that follicle counts will hardly change from one category to another when
      repeatedly carried out. CONCLUSIONS: Determination of antral follicle numbers by
      both 2D and 3D TVS is adequate with regard to the intra- and interobserver
      reproducibility. The between-method reproducibility of follicle counts measured
      both by 2D and 3D ultrasound is moderate. When higher follicle counts are
      observed both interobserver and between-method reproducibilities tend to decline.
      If used in categorical classifications, ultrasound-based follicle counts appear
      to have a high level of agreement between and within observers.

PMID- 12230452
TI  - Hyperinsulinemia and uterine perfusion in patients with polycystic ovary
      syndrome.
AB  - OBJECTIVE: To determine whether hyperinsulinemia has a negative effect on uterine
      blood supply in patients with polycystic ovary syndrome (PCOS). METHODS: Sixty
      three patients with normal body mass index were included prospectively in the
      study: 48 had clinical and hormonal features of PCOS and 15 were normo-ovulatory.
      All patients underwent Doppler flow measurement of the uterine artery, and
      determination of serum concentrations of luteinizing hormone, follicle
      stimulating hormone, prolactin, estradiol, androgens, insulin and C-peptide
      during the early follicular phase of the menstrual cycle. The 48 PCOS-patients
      were divided into two groups according to the pulsatility index (PI) value of the
      uterine artery: Group 1, PI < 3; Group 2, PI >or= 3 and the groups were compared.
      RESULTS: The mean PI of the uterine artery (3.01 +/- 1.0 vs. 1.93 +/- 0.3,
      respectively) and fasting levels of insulin (50.9 +/- 9.3 vs. 40.3 +/- 10.9) and
      C-peptide (366.9 +/- 118.4 vs. 243.6 +/- 120.3) of PCOS-patients were
      significantly higher than those of the control group. No correlation was found
      between insulinemia and C-peptide and PI of the uterine artery and no significant
      difference was found in insulin and C-peptide levels among the two groups of PCOS
      affected patients. Only the serum level of dehydroepiandrosterone sulfate was
      significantly higher in Group 2, and a direct correlation was found between PI
      values of the uterine artery and DHEAS plasma levels. CONCLUSION: Insulin and C
      peptide do not seem to interfere with uterine perfusion in PCOS-affected
      patients.

PMID- 12230453
TI  - Three-dimensional sonographic and power Doppler characterization of ovaries in
      late follicular phase.
AB  - OBJECTIVE: To determine ovarian blood flow characteristics using three
      dimensional power Doppler ultrasound. METHODS: We examined 30 patients (30
      cycles) prior to the start of their in vitro fertilization treatment in the late
      follicular phase using three-dimensional power Doppler ultrasound. The volume,
      vascularization index, flow index, vascularization flow index, mean grayness and
      the presence of the dominant follicle were determined for each ovary separately.
      RESULTS: The dominant follicle could be detected in 24 out of 30 cycles (80.0%).
      The volume of the dominant ovary was 9.9 (standard deviation, 4.0) cm3 and the
      volume of the non-dominant ovary 6.8 (standard deviation, 2.8) cm3 (P < 0.001).
      Mean grayness in the dominant ovary was 43.3 (standard deviation, 5.0) and in the
      non-dominant 47.2 (standard deviation, 4.0) (P < 0.001), but no other differences
      could be observed between dominant and non-dominant ovaries. The shell with a
      diameter of 2 mm surrounding the dominant follicle had a higher vascularization
      index (mean, 9.0; standard deviation, 5.9) and vascularization flow index (mean,
      4.2; standard deviation, 2.8) than the whole dominant ovary (mean, 5.5; standard
      deviation, 2.5 and mean, 2.5; standard deviation, 1.3, respectively) (P = 0.003
      and 0.002, respectively). In the cycles without a dominant follicle (n = 6), flow
      index (mean, 50.0; standard deviation, 5.9) and vascularization flow index (mean,
      7.3; standard deviation, 6.2) on the left side were higher than on the right side
      (mean, 40.2; standard deviation, 3.1; mean, 1.5; standard deviation, 1.4; P
      values 0.013 and 0.046, respectively). CONCLUSION: In the dominant ovary, the
      volume was higher and mean grayness lower than in the non-dominant ovary. The
      vascularization index in the shell surrounding the dominant follicle was higher
      than the average vascularization index in the whole dominant ovary. In addition,
      there were differences in the vascularization and flow indices between right and
      left ovaries, which may be related to the anatomical difference in the venous
      drainage between right and left ovaries.

PMID- 12230454
TI  - Fetal gender: antenatal discrepancy between phenotype and genotype.
AB  - Sexual discrepancy is reported in both 46,XY females and 46,XX males, and most
      diagnoses of sex reversal are made in the postpubertal period. We report three
      cases of sexual discrepancy, which were revealed by karyotyping following genetic
      amniocentesis, chorionic villus sampling and fetal blood sampling. The etiologies
      of 46,XX male, 45,X male and 46,XY female subjects are reviewed. When sexual
      discrepancy between fetal karyotype and ultrasonographic fetal phenotype is
      encountered, sample error and placental mosaicism should be excluded. A detailed
      fetal ultrasound examination should be performed to check for syndromic gender
      discrepancy. When repeat karyotyping is indicated, localization of the Sox
      related Y chromosome gene should be carried out.

PMID- 12230455
TI  - Three-dimensional prenatal diagnosis of frontonasal malformation and unilateral
      cleft lip/palate.
AB  - Frontonasal malformation includes a spectrum of anomalies involving the eyes,
      nose, lips, forehead and brain. We present a case in which a fetal labial cleft
      was initially identified using traditional two-dimensional sonography. Three
      dimensional sonography with multiplanar reconstruction and surface-rendering were
      essential to establish the diagnosis of frontonasal malformation with severe
      nasal hypoplasia and unilateral complete cleft lip/palate.

PMID- 12230456
TI  - Hypophosphatasia associated with increased nuchal translucency: a report of two
      affected pregnancies.
AB  - Perinatal hypophosphatasia is a lethal autosomal recessive skeletal abnormality
      with a birth prevalence of about 1 per 100 000. It is characterized by deficiency
      of the tissue-nonspecific isoenzyme of alkaline phosphatase causing abnormal bone
      mineralization. In the two affected fetuses from the same family ultrasound
      examination at 14 and 12 weeks, respectively, demonstrated increased nuchal
      translucency thickness, hypomineralization of the skull and spine, narrowing of
      the chest and shortening of the limbs.

PMID- 12230457
TI  - Mid-trimester fetal subdural hemorrhage: prenatal diagnosis.
AB  - A routine antenatal ultrasound examination at 20 weeks' gestation revealed a
      space-occupying lesion in the fetal right cerebral hemisphere. The borders of the
      mass were indistinct and there was no midline shift. A small collection of
      echogenic bowel was identified at the right iliac fossa. In an attempt to explain
      both findings a provisional diagnosis of a fetal blood dyscrasia was made. Fetal
      cranial magnetic resonance imaging 24 h later confirmed the diagnosis of a
      subdural hemorrhage. Subsequent fetal blood sampling confirmed severe fetal
      thrombocytopenia. To our knowledge this is the first report of the antenatal
      diagnosis of spontaneous mid-trimester fetal subdural hemorrhage.

PMID- 12230458
TI  - Marked splenomegaly in fetal cytomegalovirus infection: detection supported by
      three-dimensional power Doppler ultrasound.
AB  - An enlarged fetal spleen can be associated with fetal infection, anemia and
      different syndromes but its prenatal diagnosis is rare. We report on a diagnosis
      of splenomegaly at 32 weeks' gestation in a fetus which was found to be affected
      by cytomegalovirus infection. An enlarged spleen was suspected when the stomach
      was found to be displaced anteriorly and medially and the diagnosis was supported
      on visualization of the splenic vessels by color and three-dimensional power
      Doppler ultrasound. The patient had been referred because of fetal growth
      restriction and intracerebral anomalies and the additional finding of
      splenomegaly was highly suspicious for cytomegalovirus infection. This was
      confirmed by positive maternal serology and by neonatal virus excretion in urine.
      Retrospectively, examination of stored blood samples from 9 and 23 weeks'
      gestation revealed an early cytomegalovirus infection. Antenatal and neonatal
      magnetic resonance imaging examinations showed microcephaly, lissencephaly and
      the presence of microcalcifications. At the age of 9 months, the child suffers
      from severe neurological impairment and blindness due to severe optical atrophy.
      This case emphasizes that color Doppler and three-dimensional power Doppler
      ultrasound can facilitate the antenatal diagnosis of splenomegaly and can help to
      delineate the spleen from the similar-looking neighboring liver.

PMID- 12230459
TI  - Three-dimensional ultrasound in the diagnosis of left upper limb amelia and right
      upper limb deficiency at 10 weeks' gestation.

PMID- 12230460
TI  - Identification of unexpected parental Robertsonian (13q;14q) translocations
      following prenatal sonographic detection of holoprosencephaly.

PMID- 12230461
TI  - Glutaric aciduria (type I): prenatal ultrasonographic findings.

PMID- 12230462
TI  - 'Whirlpool' sign in the prenatal diagnosis of intestinal volvulus.

PMID- 12230463
TI  - Prenatal upper gastrointestinal bleeding.

PMID- 12230464
TI  - Peritoneal tuberculosis simulating ovarian cancer.

PMID- 12230465
TI  - Tent-shaped mouth as a presenting symptom of congenital myotonic dystrophy.

PMID- 12230467
TI  - 1st class ticket to class I: protein toxins as pathfinders for antigen
      presentation.
AB  - A number of bacterial toxins have evolved diverse strategies for crossing
      membrane barriers in order to reach their substrates in the mammalian cytosol.
      Recent studies show that this property can be exploited for the delivery of fused
      antigens into the major histocompatibility complex class I-restricted
      presentation pathway, with the goal of eliciting a specific immune response. Here
      we discuss the peculiarities of the trafficking pathways of a variety of toxins,
      and how these may allow the toxins to be used as delivery vehicles for
      therapeutic and diagnostic purposes.

PMID- 12230468
TI  - Lipid rafts and assembly of enveloped viruses.
AB  - The plasma membrane, late secretory pathway and endosomal compartments contain
      detergent-insoluble raft microdomains that are enriched in sphingolipids and
      cholesterol. Rafts are currently an intensively studied topic of cell biology,
      and raft involvement has been implicated in numerous cellular processes. A number
      of recent reports have localized structural proteins of several enveloped viruses
      to rafts, thus raising the possibility that rafts also play a role in the
      assembly and budding of viruses, but what exactly that role might be is still
      unknown.

PMID- 12230469
TI  - Interferon-induced mx proteins: dynamin-like GTPases with antiviral activity.
AB  - Mx proteins are interferon-induced GTPases that belong to the dynamin superfamily
      of large GTPases. Similarities include a high molecular weight, a propensity to
      self-assemble, a relatively low affinity for GTP, and a high intrinsic rate of
      GTP hydrolysis. A unique property of Mx GTPases is their antiviral activity
      against a wide range of RNA viruses, including bunya- and orthomyxoviruses. The
      human MxA GTPase accumulates in the cytoplasm of interferon-treated cells, partly
      associating with the endoplasmic reticulum. In the case of bunyaviruses, MxA
      interferes with transport of the viral nucleocapsid protein (N) to the Golgi
      compartment, the site of virus assembly. In the case of Thogoto virus (an
      orthomyxovirus), MxA prevents the incoming viral nucleocapsids from being
      transported into the nucleus, the site of viral transcription and replication. In
      both cases, the GTP-binding and carboxy-terminal effector functions of MxA are
      required for target recognition. In general, Mx GTPases appear to detect viral
      infection by sensing nucleocapsid-like structures. As a consequence, these viral
      components are trapped and sorted to locations where they become unavailable for
      the generation of new virus particles.

PMID- 12230470
TI  - Human macrophages accumulate HIV-1 particles in MHC II compartments.
AB  - Macrophages are important targets for HIV-1 infection and harbor the virions in
      an as yet unidentified organelle. To determine the location of HIV-1 in these
      cells, an extensive analysis of primary human macrophages infected in vitro with
      HIV-1 was carried out by immuno-electron microscopy. Virus particles were found
      to accumulate in intracellular multivesicular compartments which were enriched in
      major histocompatibility complex class II molecules and CD63. These features are
      characteristics of major histocompatibility complex class II compartments where
      maturing class II molecules acquire their peptide cargo. The membrane-delimited,
      electron-dense virus particles of 100-110 nm diameter labeled strongly for HIV-1
      p24 antigen, major histocompatibility complex class II molecules, CD63 and, to a
      lesser extent for HIV-1 gp120 envelope protein and Lamp 1. Our data suggest that
      virus particles may access the lumen of the major histocompatibility complex
      class II compartment by budding from the limiting membrane, thus acquiring
      proteins of this membrane such as class II and CD63. Viral assembly and budding
      would therefore occur in macrophages by a process similar to the formation of the
      internal vesicles in multivesicular bodies and at the same location. This could
      account for the particular content in lipids and proteins previously found in the
      membrane wrapping HIV particles. Our observations also suggest direct fusion of
      the virus containing major histocompatibility complex class II compartment with
      the plasma membrane, leading to massive release of viral particles into the
      extracellular medium.

PMID- 12230471
TI  - An ER membrane protein, Sop4, facilitates ER export of the yeast plasma membrane
      [H+]ATPase, Pma1.
AB  - We have analyzed the mechanism by which Sop4, a novel ER membrane protein,
      regulates quality control and intracellular transport of Pma1-7, a mutant plasma
      membrane ATPase. At the restrictive temperature, newly synthesized Pma1-7 is
      targeted for vacuolar degradation instead of being correctly delivered to the
      cell surface. Loss of Sop4 at least partially corrects vacuolar mislocalization,
      allowing Pma1-7 routing to the plasma membrane. Ste2-3 is a mutant pheromone
      receptor which, like Pma1-7, is defective in targeting to the cell surface,
      resulting in a mating defect. sop4delta suppresses the mating defect of ste2-3
      cells as well as the growth defect of pma1-7. Visualization of newly synthesized
      Pma1-7 in sop4delta cells by indirect immunofluorescence reveals delayed export
      from the ER. Similarly, ER export of wild-type Pma1 is delayed in the absence of
      Sop4 although intracellular transport of Gas1 and CPY is unaffected. These
      observations suggest a model in which a selective increase in ER residence time
      for Pma1-7 may allow it to achieve a more favorable conformation for subsequent
      delivery to the plasma membrane. In support of this model, newly synthesized Pma1
      7 is also routed to the plasma membrane upon release from a general block of ER
      to-Golgi transport in sec13-1 cells.

PMID- 12230472
TI  - Ligand-independent degradation of epidermal growth factor receptor involves
      receptor ubiquitylation and Hgs, an adaptor whose ubiquitin-interacting motif
      targets ubiquitylation by Nedd4.
AB  - Ligand-dependent endocytosis of the epidermal growth factor receptor (EGFR)
      involves recruitment of a ubiquitin ligase, and sorting of ubiquitylated
      receptors to lysosomal degradation. By studying Hgs, a mammalian homolog of a
      yeast vacuolar-sorting adaptor, we provide information on the less understood,
      ligand-independent pathway of receptor endocytosis and degradation. Constitutive
      endocytosis involves receptor ubiquitylation and translocation to Hgs-containing
      endosomes. Whereas the lipid-binding motif of Hgs is necessary for receptor
      endocytosis, the ubiquitin-interacting motif negatively regulates receptor
      degradation. We demonstrate that the ubiquitin-interacting motif is endowed with
      two functions: it binds ubiquitylated proteins and it targets self-ubiquitylation
      by recruiting Nedd4, an ubiquitin ligase previously implicated in endocytosis.
      Based upon the dual function of the ubiquitin-interacting motif and its wide
      occurrence in endocytic adaptors, we propose a ubiquitin-interacting motif
      network that relays ubiquitylated membrane receptors to lysosomal degradation
      through successive budding events.

PMID- 12230473
TI  - AP-1A and AP-3A lysosomal sorting functions.
AB  - Heterotetrameric adaptor-protein complexes AP-1A and AP-3A mediate protein
      sorting in post-Golgi vesicular transport. AP-1A and AP-3A have been localized to
      the trans-Golgi network, indicating a function in protein sorting at this
      compartment. AP-3A appears to mediate trans-Golgi network-to-lysosome and also
      endosome-to-lysosome protein sorting. AP-1A is thought to be required for both
      trans-Golgi network-to-endosome transport and endosome-to-trans-Golgi network
      transport. However, the recent discovery of a role for monomeric GGA (Golgi
      localized gamma-ear containing, ARF binding protein) adaptor proteins in trans
      Golgi network to endosome protein transport has brought into question the long
      discussed trans-Golgi network-to-endosome sorting function of AP-1A. Murine
      cytomegalovirus gp48 contains an unusual di-leucine-based lysosome sorting signal
      motif and mediates lysosomal sorting of gp48/major histocompatibility complex
      class I receptor complexes, preventing exposure of major histocompatibility
      complex class I at the plasma membrane. We analyzed lysosomal sorting of
      gp48/major histocompatibility complex class I receptor complexes in cell lines
      deficient for AP-1A, AP-3A and both, to determine their sorting functions. We
      find that AP1-A and AP3-A mediate distinct and sequential steps in the lysosomal
      sorting. Both sorting functions are required to prevent MHC class I exposure at
      the plasma membrane at steady-state.

PMID- 12230475
TI  - Advancing fluid management in peritoneal dialysis.

PMID- 12230476
TI  - Impact of congestive heart failure and other cardiac diseases on patient
      outcomes.

PMID- 12230477
TI  - Approach to fluid management in peritoneal dialysis: a practical algorithm.

PMID- 12230478
TI  - Profiling of peritoneal ultrafiltration.

PMID- 12230480
TI  - Biocompatibility of icodextrin.

PMID- 12230479
TI  - Pharmacokinetics of icodextrin in peritoneal dialysis patients.
AB  - Pharmacokinetics of icodextrin in peritoneal dialysis patients. BACKGROUND:
      Icodextrin is a glucose polymer osmotic agent used to provide sustained
      ultrafiltration during long peritoneal dialysis (PD) dwells. A number of studies
      have evaluated the steady-state blood concentrations of icodextrin during
      repeated use; however, to date the pharmacokinetics of icodextrin have not been
      well studied. The current study was conducted to determine the absorption, plasma
      kinetics and elimination of icodextrin and metabolites following a single
      icodextrin exchange. METHODS: Thirteen PD patients were administered 2.0 L of
      solution containing 7.5% icodextrin for a 12-hour dwell. Icodextrin (total of all
      glucose polymers) and specific polymers with degrees of polymerization ranging
      from two to seven (DP2 to DP7) were measured in blood, urine and dialysate during
      the dwell and after draining the solution from the peritoneal cavity. RESULTS: A
      median of 40.1% (60.24 g) of the total administered dose (150 g) was absorbed
      during the 12-hour dwell. Plasma levels of icodextrin and metabolites rose during
      the dwell and declined after drain, closely corresponding to the one-compartment
      pharmacokinetic model assuming zero-order absorption and first-order elimination.
      Peak plasma concentrations (median C peak = 2.23 g/L) were observed at the end of
      the dwell (median Tmax = 12.7 h) and were significantly correlated with patients'
      body weight (R2 = 0.805, P < 0.001). Plasma levels of icodextrin and metabolites
      returned to baseline within 3 to 7 days. Icodextrin had a plasma half-life of
      14.73 hours and a median clearance of 1.09 L/h. Urinary excretion of icodextrin
      and metabolites was directly related to residual renal function (R2 = 0.679 vs.
      creatinine clearance, P < 0.01). In the nine patients with residual renal
      function, the average daily urinary excretion of icodextrin was 473 +/- 77 mg per
      mL of endogenous renal creatinine clearance. Icodextrin metabolites DP2 to DP4
      were found in the dialysate of subsequent dextrose exchanges, contributing to
      their elimination from blood. Changes in intraperitoneal concentrations of
      icodextrin metabolites during the dwell revealed a dual pattern, with a
      progressive rise in the dialysate concentration of smaller polymers (DP2 to DP4)
      and a progressive decline in the dialysate concentrations of the larger polymers
      (DP5 to DP7), suggesting some intraperitoneal metabolism of the glucose polymers.
      This increase in dialysate metabolite levels, however, did not contribute
      significantly to dialysate osmolality. In addition, some diffusion of maltose
      (DP2) from blood to dialysate may have occurred. There were no changes in serum
      insulin or glucose levels during icodextrin administration, indicating that
      icodextrin does not result in hyperglycemia or hyperinsulinemia as occurs during
      dextrose-based dialysis. Serum sodium and chloride declined in parallel with the
      rise in plasma levels of icodextrin, supporting the hypothesis that these
      electrolyte changes are the result of the increased plasma osmolality due to the
      presence of icodextrin metabolites. CONCLUSIONS: The pharmacokinetics of
      icodextrin in blood following intraperitoneal administration conforms to a
      simple, single-compartment model that can be approximated by zero-order
      absorption and first-order elimination. A small amount of intraperitoneal
      metabolism of icodextrin occurs but does not contribute significantly to
      dialysate osmolality. The metabolism of absorbed icodextrin and the resultant
      rise in plasma levels of small glucose polymers (DP2 to DP4) do not result in
      hyperglycemia or hyperinsulinemia, but may result in a small decrease in serum
      sodium and chloride.

PMID- 12230482
TI  - Use of icodextrin in high transport ultrafiltration failure.

PMID- 12230481
TI  - Review of clinical trial experience with icodextrin.

PMID- 12230483
TI  - Metabolic and laboratory effects of icodextrin.

PMID- 12230484
TI  - Early quality of life benefits of icodextrin in peritoneal dialysis.
AB  - Early quality of life benefits of icodextrin in peritoneal dialysis. BACKGROUND:
      The impact of new therapies on patient quality of life (QOL) is emerging as an
      important indicator of the value of these therapies. In patients on dialysis,
      previous QOL evaluations have focused mainly on comparative approaches between
      modalities, or on longitudinal trends within a modality, but few have evaluated
      technical innovations or introduction of new therapies. The aim of the present
      study was to assess the early effects of a new dialysis solution (icodextrin) on
      the QOL of peritoneal dialysis patients. The QOL is compared with that of
      patients on dextrose, and the impact of demographic, and clinical characteristics
      on patients' QOL is examined. METHODS: The kidney disease quality of life
      questionnaire (KDQOL) was administered to patients who participated in a phase
      III double-blind, parallel group, active-controlled trial to evaluate the
      efficacy and safety of a peritoneal dialysis (PD) solution containing icodextrin
      in comparison with dextrose PD solution. A total of 93 patients (58 icodextrin,
      and 35 dextrose) completed the questionnaire at both baseline and after 13 weeks.
      In addition to patients QOL, patients' demographic and clinical characteristics
      were recorded at both baseline and 13 weeks. RESULTS: Mean change scores from
      baseline to 13 weeks of icodextrin patients were substantially higher (> or =5)
      than dextrose, particularly with respect to general health perception, physical
      functioning, role-physical, and many KDQOL symptom items such as lack of
      strength, washed out or drained, lack of appetite, faintness or dizziness, dry
      skin, cramps after an exchange or treatment, cramps during an exchange or
      treatment, and muscle spasms or twitching. At 13 weeks, icodextrin patients had
      significantly improved symptoms, and rated their health in general higher than
      those patients in the dextrose group. Upon multivariate analysis, icodextrin
      contributed significantly to the improvement of patients' mental health, general
      health, and symptoms such as muscle spasms or twitching, cramps during an
      exchange or treatment, cramps after an exchange or treatment, itchy skin, and
      faintness or dizziness. CONCLUSIONS: Peritoneal dialysis patients treated with
      icodextrin experienced substantial quality of life improvement at 13 weeks after
      the start of treatment when compared to dextrose patients. Further research is
      necessary to determine patients' quality of life over time in a longitudinal
      study setting.

PMID- 12230485
TI  - Future of icodextrin as an osmotic agent in peritoneal dialysis.

PMID- 12230486
TI  - In situ high temperature microscopy study of the surface oxidation and phase
      transformations in titanium alloys.
AB  - Two popular commercial titanium alloys, Ti-6Al-4V and Ti-6Al-2Sn-4Zr-2Mo-0.08Si,
      were used for in situ high temperature microscopy study. The experiments were
      performed on an optical microscope equipped with high temperature stage using
      both normal and florescence lights. Two kinds of experiments were performed, at
      continuous heating/cooling with different rates and in isothermal conditions at
      different temperatures. The changes taking place on the sample surface during the
      experiments were monitored. The morphology of the alpha ==> beta ==> alpha phase
      transformation was recorded at different heat treatment conditions using the
      effect of thermal etching. An effect of sample surface oxidation and deoxidation
      was observed during continuous heating. The appearance and disappearance of
      ordered titanium oxides Ti3O and Ti2O are discussed based on the phase
      equilibrium diagram. The kinetics of the surface oxidation was monitored in both
      isothermal and continuous cooling conditions.

PMID- 12230487
TI  - On the influence of imaging conditions and algorithms on the quantification of
      surface topography.
AB  - The influence of the microscopical magnification resulting in different voxel
      size and shape and of the algorithm on parameters used for the quantification of
      the surface topography is studied using topographical images obtained by confocal
      laser scanning microscopy. Fracture surfaces and wire-eroded surfaces of steel
      were used as samples. The values obtained for the global topometry parameters
      normalized surface area, mean profile segment length and fractal dimension depend
      with different degrees on the microscopic magnification and on the algorithm used
      to compute these values. The topometry values can only be used to establish
      correlations between the topography and materials properties and for the
      modelling of surface generating processes if the imaging and computing details
      are given.

PMID- 12230488
TI  - Analytical electron microscopy as a tool for accessing colloid formation process
      in natural waters.
AB  - Analytical electron microscopy was used to characterize aquatic iron-rich
      colloids. We focused our attention on a redox transition medium in the drainage
      water of a peat soil. In the anoxic peat water, observations by transmission
      electron microscopy and associated energy dispersive analyses (TEM-EDS) highlight
      the presence of spherical entities (approximately 100-600 nm), containing only
      traces of iron. The increase of dissolved oxygen concentration favours the
      formation of iron oxy(hydr)oxides. In the oxygenated drain, particles with the
      same morphology and size range are present. Statistical TEM-EDS analyses show
      that they represent the only colloidal form of iron in the drain samples.
      Nevertheless, although Fe-K peaks appear clearly on EDS spectra, the proportion
      of iron in these colloids reaches at most 4% at. (whereas C + O > 90% at.).
      Structural information completes this study. Both electron spectroscopic imaging
      (ESI) and electron energy-loss spectroscopy (EELS) reveal the disparity between
      element distributions within the drain entities. Iron and calcium are preferably
      distributed on the outer sphere of the particle, whereas carbon and oxygen follow
      the theoretical variation of the signal intensity within a plain sphere. The
      implication of organic matter as nucleation site for iron precipitation is
      spectacularly demonstrated by the presence of nanometre-sized iron-rich phases
      highlighted by EELS line scans.

PMID- 12230489
TI  - The smooth fractionator.
AB  - A modification of the general fractionator sampling technique called the smooth
      fractionator is presented. It may be used in almost every situation in which
      sampling is performed from distinct items that are uniquely defined, often they
      are physically separated items or clusters like pieces, blocks, slabs, sections,
      etc. To each item is associated a 'guesstimate' or an associated variable with a
      more-or-less close--and possibly biased--relationship to the content of the item.
      The smooth fractionator is systematic sampling among the items arranged according
      to the guesstimates in a unique, symmetric sequence with one peak and minimal
      jumps. The smooth fractionator is both very simple to implement and so efficient
      that it should probably always be used unless the natural sequence of the
      sampling items is equally smooth. So far, there is no theory for the prediction
      of the efficiency of smooth fractionator designs in general, and their properties
      are therefore illustrated with a range of real and simulated examples. At the
      cost of a slightly more elaborate sampling scheme, it is, however, always
      possible to obtain an unbiased estimate of the real precision and of some of the
      variance components. The only real practical problem for always obtaining a high
      precision with the smooth fractionator is specimen inhomogeneity, but that is
      detectable at almost no extra cost. With careful designs and for sample sizes of
      about 10, the sampling variation for the primary, smooth fractionator sampling
      step may in practice often be small enough to be ignored.

PMID- 12230490
TI  - Stereological estimation of the total number of ECL cells and related parameters
      using the smooth, vertical fractionator in the rat oxyntic mucosa.
AB  - During the last 10 years many attempts have been made to estimate the number of
      enterochromaffin-like (ECL) cells in various animal studies. This is the first
      presentation of an unbiased stereological estimator of the total number of
      histamine-positive ECL cells per rat and linked to estimators of related
      parameters: total volume of the oxyntic mucosa, total oxyntic mucosal surface
      area, total oxyntic serosal surface area, surface amplification factor, average
      thickness of the oxyntic mucosa, total and mean volume of the ECL cells, total
      number of oxyntic glands and pits, mean number of ECL cells per gland, and mean
      number of ECL cells and glands per oxyntic serosal surface area. This study is
      the first application of the smooth fractionator and includes a description of
      all sources of sampling variance in the smooth fractionator design with newly
      developed predictors.

PMID- 12230491
TI  - Precision of circular systematic sampling.
AB  - In design stereology, many estimators require isotropic orientation of a test
      probe relative to the object in order to attain unbiasedness. In such cases,
      systematic sampling of orientations becomes imperative on grounds of efficiency
      and practical applicability. For instance, the planar nucleator and the vertical
      rotator imply systematic sampling on the circle, whereas the Buffon-Steinhaus
      method to estimate curve length in the plane, or the vertical designs to estimate
      surface area and curve length, imply systematic sampling on the semicircle. This
      leads to the need for predicting the precision of systematic sampling on the
      circle and the semicircle from a single sample. There are two main prediction
      approaches, namely the classical one of G. Matheron for non-necessarily periodic
      measurement functions, and a recent approach based on a global symmetric model of
      the covariogram, more specific for periodic measurement functions. The latter
      approach seems at least as satisfactory as the former for small sample sizes, and
      it is developed here incorporating local errors. Detailed examples illustrating
      common stereological tools are included.

PMID- 12230493
TI  - Gene transfer of secreted-type modified interleukin-18 gene to B16F10 melanoma
      cells suppresses in vivo tumor growth through inhibition of tumor vessel
      formation.
AB  - Interleukin-18 is a novel cytokine identified as a strong inducer of interferon
      gamma. Interleukin-18 has been shown to have similar bioactivities to interleukin
      12 and to have antitumor efficacy in experimental models. In this study, we
      investigated whether the introduction of the interleukin-18 gene to B16F10
      melanoma cells can induce antitumor response or not. Before the transfection, we
      modified the interleukin-18 gene to enable transfected tumor cells to secrete
      bioactive interleukin-18, because interleukin-18 does not have a signal sequence
      and requires processing by the interleukin-1 converting enzyme to attain the
      mature form. We found that B16 melanoma cells transduced with hybrid cDNA
      consisting of the interferon-beta signal sequence and mature interleukin-18
      sequence, but not native interleukin-18, secreted a large amount of interleukin
      18 and exhibited retarded tumor growth when injected in syngeneic mice. The
      antitumor effect was mostly abrogated by administration of anti-interferon-gamma
      antibody, but was not affected by in vivo depletion of CD8+ T cells or natural
      killer cells. Histologic analysis revealed that vascularization was markedly
      reduced and that necrosis was extensively induced in interleukin-18-secreting
      B16F10 melanoma (B16/IL18) tissues, whereas abundant tumor vessel formation was
      observed in B16/IL18 tissues of interferon-gamma-neutralized mice. We also found
      that chemokines, interferon-inducible protein-10 and monokine induced by
      interferon-gamma, were produced in B16/IL18 tissues and that the expression of
      both chemokines was dependent on that of interferon-gamma in the tumor tissues.
      Further, we showed that B16 melanoma cells secreted both chemokines in response
      to interferon-gamma. In addition, the expression of angiogenin, an angiogenic
      factor of melanoma, in B16 melanoma cells was reduced by interferon-gamma
      treatment. These results indicate that gene transfer of secreted-type interleukin
      18 to B16F10 melanoma cells is a useful method of triggering an antitumor
      response without any systemic adverse effects and that the antitumor efficacy is
      mainly mediated by antiangiogenic activity, which is possibly involved in at
      least two dynamic changes induced by interferon-gamma inside B16 melanoma cells:
      the upregulation of antiangiogenic chemokines, interferon-inducible protein-10
      and monokine induced by interferon-gamma, and the downregulation of angiogenic
      factor, angiogenin.

PMID- 12230494
TI  - Endothelin-1 decreases basic apoptotic rates in human melanoma cell lines.
AB  - Normal human melanocytes respond to endothelin-1 with induced proliferation and
      differentiation. Whereas in cultured melanoma cells the predominant endothelin
      receptor, ET(B)-R, is consistently downregulated, ET(B)-R upregulation was
      recently reported for melanoma tumors. Contrary to the pro-survival activity
      described for endothelin in vascular cells, a proapoptotic activity of endothelin
      1 has been reported for melanoma cells, in previous studies. We therefore
      investigated the role of endothelin for melanoma cells with respect to apoptosis
      and proliferation. Treatment with 10 nM endothelin-1 was a strong mitogenic
      signal for normal human melanocytes, which responded with a 4-6-fold increase of
      thymidine incorporation, whereas the response was only 1.2-fold for SK-Mel-19,
      the melanoma cell line characterized by the highest ET(B)-R expression, and it
      was even less in other cell lines. Determination of the apoptotic rates revealed
      that endothelin-1 significantly reduced basic apoptotic rates to 75% both in SK
      Mel-19 and in normal melanocytes. After cell synchronization, an antiapoptotic
      effect of endothelin-1 was seen in five of seven cell lines investigated. In the
      cell line Bro, which showed no response and which lacks ET(B)-R expression,
      responsibility could be restored by overexpression of ET(B)-R after stable
      transfection, indicating that the effectors of the endothelin-1 signal cascade
      were active in these cells, and that the antiapoptotic effect of endothelin-1 is
      mediated in a receptor-specific way. This antiapoptotic activity of endothelin
      for melanoma cells combined with upregulation of endothelin receptors in the
      tumor may be a crucial step for melanoma progression.

PMID- 12230495
TI  - Regulation of Fas-mediated apoptosis by N-ras in melanoma.
AB  - Oncogenic ras has been shown to downregulate Fas receptor expression and increase
      Fas ligand expression and thus contribute to resistance to Fas-mediated cell
      death in several cell types. The effects of ras on Fas-mediated apoptosis have
      not been studied in melanoma. We studied the effects of activated N-ras by
      measuring Fas, Fas ligand, and FLIP expression as well as susceptibility to Fas
      ligand-induced cell death in transfectants of WM35, a radial growth phase human
      melanoma cell line. Based on quantitative polymerase chain reaction and
      fluorescence-activated cell sorter analysis, we found that the ras transfectants
      expressed less Fas mRNA and surface Fas receptor. Cr51 release cytotoxicity
      assays demonstrated less susceptibility to Fas-mediated apoptosis in ras
      transfectants, correlating with the Fas mRNA and protein expression results. Ras
      inhibition with the specific inhibitor FTI-277 showed that downregulation of Fas
      in the ras transfectants could be reversed. This correlates with cytotoxicity
      experiments showing that ras inhibition increases susceptibility to Fas-mediated
      apoptosis. The control transfectants expressed FLIP but ras did not affect FLIP
      expression. The control and ras transfectants did not express Fas ligand as
      demonstrated by reverse transcriptase polymerase chain reaction and fluorescence
      activated cell sorter analysis. Cytotoxicity assays further confirmed that these
      melanoma ras transfectants do not express functional Fas ligand. These results
      suggest that ras contributes to tumor progression by decreasing susceptibility to
      Fas-mediated cell death at least in part through downregulation of Fas receptor
      at the transcriptional level.

PMID- 12230496
TI  - Cloning and characterization of the expression pattern of a novel splice product
      MIA (splice) of malignant melanoma-derived growth-inhibiting activity (MIA/CD
      RAP) [corrected].
AB  - Melanoma-inhibiting activity/cartilage-derived retinoic acid-sensitive protein, a
      11 kDa protein, is mainly expressed in cartilage during embryogenesis, and is
      related to invasion, metastasis, and immunomodulation of melanoma and glioma
      cells in vivo and in vitro. Here, we describe an alternative splice product of
      this gene termed melanoma-inhibiting activity (splice), lacking exon 2 of the
      original protein. A predicted frameshift by alternate splicing results in a
      unique C-terminal portion of the protein. Consistent with this, a protein
      migrating at the predicted molecular weight of the splice form (3.5 kDa) was
      detected using an N-terminal specific antibody. This band was undetectable when
      using a C-terminal specific antibody. In addition, we describe the expression
      pattern of melanoma-inhibiting activity (splice) in different human tumors.
      Expression was shown in tissue samples of five of six primary melanomas, 11 of 12
      primary sites of metastatic melanomas, 10 of 10 systemic metastases of melanomas,
      four of four central nervous system metastases of melanomas, six of eight primary
      melanoma cultures, and five of five melanoma cell lines. Only a faint signal was
      obtained in tissue samples of five of six naevi. Interestingly, seven of eight
      nonmelanocytic tissue samples and five of seven glioma cell lines showed weak
      expression of melanoma-inhibiting activity (splice). Approaching first functional
      aspects, reverse transcriptase-polymerase chain reaction showed weak expression
      of melanoma-inhibiting activity (splice) in relation to melanoma-inhibiting
      activity in nonmelanocytic and strong expression in melanocytic cells. Staining
      with a specific anti-serum raised against a synthetic peptide resembling the
      amino acid sequence of melanoma-inhibiting activity (splice) showed a more
      nuclear staining pattern in comparison with melanoma-inhibiting activity.
      Furthermore, incubation of melanoma and glioma cell cultures with transforming
      growth factor-beta2 showed inverse regulation of the mRNA of melanoma-inhibiting
      activity and melanoma-inhibiting activity (splice), both suggesting also a
      different function within the physiologic role of this unique family of proteins.
      Melanoma-inhibiting activity (splice) has no homology to any other known protein
      so far. Whereas the biologic function of melanoma-inhibiting activity (splice) is
      not clear yet, it might provide a relevant diagnostic and therapeutic tool for
      malignant melanomas.

PMID- 12230497
TI  - Inverse association between melanoma and previous vaccinations against
      tuberculosis and smallpox: results of the FEBIM study.
AB  - Various forms of immunotherapy utilizing bacille Calmette-Guerin vaccine or
      vaccinia vaccine have been evaluated in clinical trials on melanoma patients. The
      effect of the "natural" application of these vaccinations, administered to
      provide protection against tuberculosis and smallpox, has, however, never been
      studied in epidemiologic investigations on risk factors for melanoma. In a case
      control study comprising 11 institutions in seven countries we recruited 603
      incident melanoma cases and 627 population controls frequency matched to the
      cases with respect to sex, age, and ethnic origin within each center to assess
      this relationship to obtain insights into the prevention of melanoma. Exposure
      information, incorporating also detailed ascertainment of potential confounding
      variables, was obtained in standardized personal interviews at the study
      subject's home. We found an inverse association between melanoma risk and
      previous bacille Calmette-Guerin vaccine/vaccinia vaccination depicted by an
      adjusted odds ratio of 0.44 (95% confidence interval: 0.26-0.72) for those
      vaccinated against tuberculosis and smallpox compared with subjects without a
      positive history of either vaccination. A variety of subgroup analyses showing a
      consistent pattern of results make it unlikely that the observed inverse
      association is a spurious finding. We conclude that bacille Calmette-Guerin
      vaccination and vaccinia vaccination may lower melanoma risk. Current immunologic
      theory of melanoma development provides a sound basis for understanding the
      biologic plausibility of the findings that have to be confirmed in future
      studies.

PMID- 12230498
TI  - Agonists of peroxisome proliferator-activated receptor gamma inhibit cell growth
      in malignant melanoma.
AB  - Peroxisome proliferator-activated receptor gamma is a member of the nuclear
      receptor superfamily involved in adipocyte differentiation and glucose
      homeostasis. There is evidence that peroxisome proliferator-activated receptor
      gamma may also act as a tumor suppressor. Here, we demonstrate expression of
      peroxisome proliferator-activated receptor gamma in benign melanocytic naevi,
      different variants of primary cutaneous melanomas, and melanoma metastases.
      Peroxisome proliferator-activated receptor gamma protein and peroxisome
      proliferator-activated receptor gamma1 mRNA were also detected in human melanoma
      cell lines. The peroxisome proliferator-activated receptor gamma specific
      agonists 15-deoxy-Delta12,14-prostaglandin J2, troglitazone, and rosiglitazone
      dose-dependently inhibited cell proliferation in four melanoma cell lines,
      whereas a specific agonist of peroxisome proliferator-activated receptor alpha
      had no such effect. At a concentration of 50 microM rosiglitazone, the most
      potent peroxisome proliferator-activated receptor gamma agonist tested suppressed
      cell growth by approximately 90%. Apoptosis could be induced in melanoma cell
      lines by incubation with tumor-necrosis-factor-related apoptosis-inducing ligand.
      In contrast, the growth inhibitory effect of peroxisome proliferator-activated
      receptor gamma activation was independent of apoptosis and seemed to occur
      primarily through induction of cell cycle arrest. Our data indicate that melanoma
      cell growth may be modulated through peroxisome proliferator-activated receptor
      gamma.

PMID- 12230499
TI  - Differentiation of murine melanocyte precursors induced by 1,25-dihydroxyvitamin
      D3 is associated with the stimulation of endothelin B receptor expression.
AB  - The effects of 1,25-dihydroxyvitamin D3 on the differentiation of immature
      melanocyte precursors were studied. The NCC-/melb4 cell line is an immature
      melanocyte cell line established from mouse neural crest cells. 1,25
      Dihydroxyvitamin D3 inhibited the growth of NCC-/melb4 cells at concentrations
      higher than 10(-8) m. That growth inhibition was accompanied by the induction of
      tyrosinase and a change in L-3,4-dihydroxyphenylalanine reactivity from negative
      to positive. Electron microscopy demonstrated that melanosomes were in more
      advanced stages after 1,25-dihydroxyvitamin D3 treatment. In primary cultures of
      murine neural crest cells, L-3,4-dihydroxyphenylalanine-positive cells were
      increased after 1,25-dihydroxyvitamin D3 treatment. These findings indicate that
      1,25-dihydroxyvitamin D3 stimulates the differentiation of immature melanocyte
      precursors. Moreover, immunostaining and reverse transcription-polymerase chain
      reaction analysis revealed that endothelin B receptor expression was induced in
      NCC-/melb4 cells following treatment with 1,25-dihydroxyvitamin D3. The induction
      of endothelin B receptor by 1,25-dihydroxyvitamin D3 was also demonstrated in
      neural crest cell primary cultures, but not in mature melanocytes. The expression
      of microphthalmia-associated transcription factor was induced in NCC-/melb4 cells
      treated with 1,25-dihydroxyvitamin D3 and endothelin 3, but not by 1,25
      dihydroxyvitamin D3 alone, suggesting that endothelin 3 may stimulate the
      expression of the microphthalmia-associated transcription factor gene after
      binding to the endothelin B receptor induced by 1,25-dihydroxyvitamin D3. These
      findings suggest a regulatory role for vitamin D3 in melanocyte development and
      melanogenesis, and may also explain the working mechanism of vitamin D3 in the
      treatment of vitiligo.

PMID- 12230500
TI  - Ketoconazole suppresses interleukin-4 plus anti-CD40-induced IgE class switching
      in surface IgE negative B cells from patients with atopic dermatitis.
AB  - We previously reported that antimycotic agent ketoconazole suppressed interleukin
      4 production in T cells from patients with atopic dermatitis. We herein studied
      if ketoconazole may suppress B cell IgE class switching. Interleukin-4 plus anti
      CD40-induced IgE secretion was enhanced in peripheral blood surface IgE- B cells
      from atopic dermatitis patients compared to those from normal donors, and the
      secretion was inhibited by ketoconazole. Ketoconazole suppressed interleukin-4
      plus anti-CD40-induced germline and mature epsilon transcripts in surface IgE- B
      cells. Ketoconazole also inhibited interleukin-4 plus anti-CD40-induced
      activation of germline epsilon promoter in human Burkitt lymphoma Ramos cells.
      The regions -171/-155 bp containing CCAAT/enhancer-binding protein element and 
      155/-109 bp containing Stat6 and nuclear factor kappaB elements were required for
      the ketoconazole-induced inhibition of the germline epsilon promoter activity.
      Ketoconazole inhibited interleukin-4 plus anti-CD40-induced enhancer activities
      of CCAAT/enhancer-binding protein and nuclear factor kappaB, and those of
      composite elements of CCAAT/enhancer-binding protein/Stat6 or of Stat6/nuclear
      factor kappaB, but did not alter that of Stat6 in Ramos cells. cAMP analog
      reversed the inhibitory effects of ketoconazole on interleukin-4 plus anti-CD40
      induced IgE secretion, germline and mature epsilon transcripts, and epsilon
      germline promoter activation. Interleukin-4 plus anti-CD40 increased
      intracellular cAMP by activating cAMP-synthesizing adenylate cyclase in surface
      IgE- B cells, and the increase was greater in the cells from atopic dermatitis
      patients than in those from normal donors. Ketoconazole suppressed interleukin-4
      plus anti-CD40-induced activation of adenylate cyclase in surface IgE- B cells.
      These results suggest that ketoconazole may suppress interleukin-4 plus anti-CD40
      induced B cell IgE class switching by inhibiting cAMP signal, and stress its
      prophylactic effects on allergic diseases.

PMID- 12230501
TI  - Mechanisms underlying the suppression of established immune responses by
      ultraviolet radiation.
AB  - The ultraviolet radiation present in sunlight is immune suppressive. Recently we
      showed that solar-simulated ultraviolet radiation (ultraviolet A + B; 295-400
      nm), applied after immunization, suppressed immunologic memory and the
      elicitation of delayed-type hypersensitivity to the common opportunistic
      pathogen, Candida albicans. Further, we found that wavelengths in the ultraviolet
      A region of the solar spectrum (320-400 nm), devoid of ultraviolet B, were
      equally effective in activating immune suppression as ultraviolet A + B
      radiation. Here we report on the mechanisms involved. Maximal immune suppression
      was found when mice were exposed to solar-simulated ultraviolet radiation 7-9 d
      post immunization. No immune suppression was found in ultraviolet-irradiated mice
      injected with monoclonal anti-interleukin-10 antibody, or mice exposed to solar
      simulated ultraviolet radiation and injected with recombinant interleukin-12.
      Suppressor lymphocytes were found in the spleens of mice exposed to ultraviolet A
      + B radiation. In addition, antigen-specific suppressor T cells (CD3+, CD4+,
      DX5+) were found in the spleens of mice exposed to ultraviolet A radiation.
      Applying liposomes containing bacteriophage T4N5 to the skin of mice exposed to
      solar-simulated ultraviolet A + B radiation, or mice exposed to ultraviolet A
      radiation, blocked immune suppression, demonstrating an essential role for
      ultraviolet-induced DNA damage in the suppression of established immune
      reactions. These findings indicate that overlapping immune suppressive mechanisms
      are activated by ultraviolet A and ultraviolet A + B radiation. Moreover, our
      findings demonstrate that ultraviolet radiation activates similar immunologic
      pathways to suppress the induction of, or the elicitation of, the immune
      response.

PMID- 12230502
TI  - Association of a new-type prostaglandin D2 receptor CRTH2 with circulating T
      helper 2 cells in patients with atopic dermatitis.
AB  - Prostaglandin D2 is known to be the major prostanoid produced by allergen
      activated mast cells, but its role in the formation of allergic diseases is not
      well established because of complexity of its receptor system and lack of
      appropriate inhibitors. We have recently identified a new-type prostaglandin D2
      receptor, named CRTH2. Studies with normal subjects have shown that CRTH2 appears
      to be selectively expressed by T helper 2 cells but not T helper 1 cells among
      circulating CD4+ lymphocytes. The exact correlation between CRTH2 and T helper 2
      cells in various disease settings and the impact of CRTH2-mediated prostaglandin
      D2 activities on various T helper 2 responses in vivo still remain to be
      elucidated, however. In this study, we investigated the correlation between CRTH2
      and T helper 2 cells among circulating CD4+ lymphocytes in normal adults and
      patients with atopic dermatitis, a T-helper-2-involving disease. The results
      showed that virtually all CRTH2+CD4+ lymphocytes had a pure T helper 2 phenotype
      and formed not all but a large proportion of circulating T helper 2 cells for
      both normal and atopic dermatitis subjects. In chemotaxis assays, peripheral
      blood CRTH2+CD4+ lymphocytes were significantly attracted by prostaglandin D2 as
      well as by a typical T-helper-2-attracting chemokine, thymus and activation
      regulated chemokine, whereas they showed little chemotactic migration toward
      typical T-helper-1-attracting chemokines, macrophage inflammatory protein 1beta
      and interferon-gamma-inducible protein 10. Furthermore, in atopic dermatitis
      patients, a preferential increase of CRTH2+ cells was noted within the disease
      related cutaneous lymphocyte-associated antigen-positive, but not the cutaneous
      lymphocyte-associated antigen-negative, CD4+ lymphocyte compartment. Our results
      suggest the involvement of the prostaglandin D2/CRTH2 system in both normal and
      pathogenic T helper 2 responses.

PMID- 12230503
TI  - Associations of tumor necrosis factor alpha and HLA polymorphisms with adult
      dermatomyositis: implications for a unique pathogenesis.
AB  - We recently reported that the -308A tumor necrosis factor alpha promoter
      polymorphism is associated with the photosensitive disorder subacute cutaneous
      lupus erythematosus and mediates an exaggerated tumor necrosis factor alpha
      response to ultraviolet B. We now sought to examine the association of this
      polymorphism with adult dermatomyositis, a photosensitive disease that exhibits
      some features in common with subacute cutaneous lupus erythematosus. Fifty adult
      patients with dermatomyositis and 239 healthy, race-matched controls were
      examined for the -308A tumor necrosis factor alpha polymorphism and the more
      common -308G allele. The frequency of the -308A allele was 0.27 in the entire
      dermatomyositis group, versus 0.14 in the controls (p = 0.003, chi2 2 x 2 table).
      Caucasians were the only racial/ethnic group in our study large enough to allow
      separate statistical analysis (47 dermatomyositis, 223 controls). The frequency
      of the -308A allele was 0.26 for dermatomyositis and 0.14 for controls (p =
      0.014). Caucasians are known to exhibit a linkage disequilibrium between -308A
      and HLA-DR3, which we previously found to be significantly enhanced in subacute
      cutaneous lupus erythematosus patients. In contrast, we now found no increase in
      the association of -308A and HLA-DR3 in Caucasians with dermatomyositis compared
      to controls. Consistent with this observation, the association of these two genes
      in dermatomyositis was significantly less than we previously reported in
      Caucasians with subacute cutaneous lupus erythematosus (p = 0.016). We conclude
      that the tumor necrosis factor -308A polymorphism is associated with
      dermatomyositis, which suggests a pathophysiologic contribution from ultraviolet
      induced production of tumor necrosis factor alpha, similar to subacute cutaneous
      lupus erythematosus. The differences in linkage with HLA-DR3, as well as several
      divergent clinical features, indicate that there are also fundamental mechanistic
      differences between dermatomyositis and subacute cutaneous lupus erythematosus.

PMID- 12230505
TI  - Spatial and kinetic factors for the transfer of head lice (Pediculus capitis)
      between hairs.
AB  - Although the global increase in pediculosis is well known, little is known about
      the exact nature of head lice (Pediculus capitis) transmission. Several
      mechanisms have been proposed such as head-to-head and fomite transmission, but
      some contention remains concerning the primary transmission route. This study
      investigated spatial and kinetic factors influencing the dynamics of hair-to-hair
      transfer to clarify further how head lice transmit from head to head. Forty-eight
      factorial experimental trials, with 10 replicates each, were conducted using 480
      freshly caught P. capitis from primary school children. In the trials, each louse
      was placed on a stationary suspended hair or a mobile hair and was presented with
      mobile or stationary hairs for transmission. All hair passes involved contact
      between the uninhabited hair and the lice. Hairs without a louse were presented
      dorsally, laterally, and ventrally to the louse. They were also passed from head
      to tail or from tail to head and were moved at speeds of 8 m and 4 m per min. The
      proportion of P. capitis transmission was highly dependent on the specific
      setting. The tail-to-head direction, slow movement, and a parallel direction all
      proved favorable for transmission. The highest transfer proportion of P. capitis
      (85%) was observed in the setting where the presented hair was laterally slow
      moving in a parallel way from tail to head. No transmission at all was observed
      under an angle of 90 degrees. Hair-to-hair P. capitis transmission occurred more
      frequently when hairs were in particular physical and kinetic relationships. This
      suggests that head lice are less likely to take advantage of many proposed fomite
      transmission scenarios and are most likely to rely on head-to-head contact for
      transmission.

PMID- 12230504
TI  - Skin-derived macrophages from Leishmania major-susceptible mice exhibit
      interleukin-12- and interferon-gamma-independent nitric oxide production and
      parasite killing after treatment with immunostimulatory DNA.
AB  - Co-administration of CpG-containing immunostimulatory oligodeoxynucleotides and
      parasite antigen protects susceptible BALB/c mice from otherwise progressive
      infection with Leishmania major. Although the protective effect of CpG-containing
      immunostimulatory oligodeoxynucleotides is clearly dependent on endogenous
      interleukin-12 and interferon-gamma production, the source of these Th1-promoting
      cytokines in infected mice is unknown. In contrast to macrophages from Leishmania
      resistant C57BL/6 mice, macrophages from susceptible BALB/c mice are
      hyporesponsive to stimulation with lipopolysaccharide and interferon-gamma. While
      studying interactions of various antigen-presenting cells with Leishmania, we
      found that BALB/c inflammatory skin macrophages, whether Leishmania-infected or
      uninfected, produced large amounts of interleukin-12 when treated with CpG
      containing immunostimulatory oligodeoxynucleotides. Like lipopolysaccharide, CpG
      containing immunostimulatory oligodeoxynucleotides induced production of
      interferon-gamma and release of nitric oxide by skin macrophages. Studies using
      skin macrophages from interleukin-12- and interferon-gamma-deficient BALB/c mice
      demonstrated that nitric oxide release was not dependent on interleukin-12 and
      interferon-gamma production. Approximately 44% and 27% of intracellular
      Leishmania major amastigotes were killed by infected skin macrophages within 72 h
      upon stimulation with CpG-containing immunostimulatory oligodeoxynucleotides and
      lipopolysaccharide, respectively. Parasite killing by macrophages was independent
      of endogenous interferon-gamma production, but was strongly enhanced by exogenous
      interferon-gamma. Parasite elimination was dependent on the induction of nitric
      oxide, however. In vivo, injection of CpG-containing immunostimulatory
      oligodeoxynucleotides into lesional skin reduced the parasite burden
      approximately 50-fold within the first 5 d of infection prior to full generation
      of a Th response. These results suggest that skin macrophages, constituting the
      principal reservoir of parasites in infected susceptible mice, produce Th1
      promoting cytokines in response to CpG-containing immunostimulatory
      oligodeoxynucleotides. In addition, CpG-containing immunostimulatory
      oligodeoxynucleotides may also act locally on skin macrophages to facilitate
      Leishmania clearance by inducing nitric oxide production.

PMID- 12230506
TI  - Mucosal addressin cell adhesion molecule 1 plays an unexpected role in the
      development of mouse guard hair.
AB  - The first wave of coat hair development is initiated around embryonic day 14 in
      the mouse. Whereas ectodysplasin and ectodermal dysplasia receptor, tumor
      necrosis factor and tumor necrosis factor receptor family molecules,
      respectively, were identified to be signals triggering this process, not much was
      known regarding their downstream molecular targets. In this report, we show that
      mucosal addressin cell adhesion molecule 1 and intercellular adhesion molecule 1
      are induced in the keratinocytes of the hair placode as a direct consequence of
      ectodermal dysplasia receptor signal, and tumor-necrosis-factor-receptor
      associated factor 6 is involved in this mucosal addressin cell adhesion molecule
      1 expression. Experiments using an in vitro culture of skin fragments
      demonstrated that ectodermal-dysplasia-receptor-induced mucosal addressin cell
      adhesion molecule 1 expression occurs at the initial phase of follicle
      development before involvement of Sonic hedgehog signal. Follicle development in
      this culture was also suppressed to some extent, though not completely, by
      addition of soluble mucosal addressin cell adhesion molecule 1/IgG-Fc chimeric
      protein, whereas monoclonal antibody that can inhibit mucosal addressin cell
      adhesion molecule 1 interaction with integrin alpha4beta7 had no effect on this
      process. These results demonstrated for the first time that the structural
      proteins, mucosal addressin cell adhesion molecule 1 and intercellular adhesion
      molecule 1, are induced by ectodermal dysplasia receptor signal and suggested the
      potential involvement of mucosal addressin cell adhesion molecule 1 in the
      morphogenesis of follicular keratinocytes.

PMID- 12230507
TI  - Exogen, shedding phase of the hair growth cycle: characterization of a mouse
      model.
AB  - The hair growth cycle is generally recognized to comprise phases of growth
      (anagen), regression (catagen), and rest (telogen). Whereas, heretofore, the hair
      shedding function has been assumed to be part of the telogen phase, using a
      laboratory mouse model and newly developed techniques for quantitative collection
      and spectroscopic determination of shed hair, we found that shedding actually
      occurs as a distinct phase. Although some shedding occurs throughout the growth
      cycle, the largest peak is coupled to anagen. Using hair dye and rhodamine
      labeling we established that the shafts that shed arise during the previous hair
      cycle. We found that over the cycle the ratio of shed overfur to shed underfur
      hair shafts varies with the cycle phase and that the shed shaft base is unique
      morphologically, having a cylindrical shape with scalloped or "nibbled" edges. By
      electron microscopy the mooring cells of the exogen root show intercellular
      separation suggesting a proteolytic process in the final shedding step. This is
      the first report describing a distinct shedding, or exogen, phase of the hair
      cycle. This study supports the notion that this phase is uniquely controlled and
      that the final step in the shedding process involves a specific proteolytic step.

PMID- 12230508
TI  - Parameters related to oxygen free radicals in human skin: a study comparing
      healthy epidermis and skin cancer tissue.
AB  - In vitro studies with tumor cells have demonstrated that oxygen free radicals are
      involved in the development of skin cancers and that variations in the body's
      defense mechanisms can modify the course of the disease. To assess the validity
      of this hypothesis in spontaneous tumors, we determined glutathione S
      transferase, superoxide dismutase, reduced and oxidized glutathione, and
      thiobarbituric acid reactive substances in healthy whole skin (n = 95), dermis (n
      = 73), and epidermis (n = 69). The values were compared with those obtained in
      three types of skin cancer: basal cell carcinoma (n = 16), squamous cell
      carcinoma (n = 6), and melanoma (n = 33). In healthy skin, glutathione S
      transferase, superoxide dismutase, reduced glutathione, and oxidized glutathione
      were higher in epidermis than in dermis, whereas thiobarbituric acid reactive
      substances were higher in dermis than in epidermis; whole skin had intermediate
      values. These results suggest that there is an induction of some anti-oxygen free
      radicals mechanisms in epidermis as a result of increased oxygen free radicals
      production. Glutathione S-transferase and thiobarbituric acid reactive substances
      were higher in all types of tumor than in healthy epidermis but oxidized
      glutathione was lower. Reduced glutathione and superoxide dismutase activity were
      lower in basal cell carcinoma and squamous cell carcinoma samples. Glutathione S
      transferase increased, whereas superoxide dismutase and thiobarbituric acid
      reactive substances decreased in melanoma samples in direct relation to the Clark
      levels. Higher glutathione S-transferase activity, particularly in the most
      invasive forms of melanoma, indicates that this type of cancer is more malignant.
      Similarly, a decrease in superoxide dismutase activity can also encourage
      progression of the tumor. These results are in accord with those from tumor cell
      cultures and could suggest new strategies (gene therapy) for managing skin
      cancer.

PMID- 12230509
TI  - Wounding of bioengineered skin: cellular and molecular aspects after injury.
AB  - Skin substitutes are increasingly being used in the treatment of difficult to
      heal wounds but their mechanisms of action are largely unknown. In this study,
      using histology, immunostaining, flow cytometry, enzyme-linked immunosorbent
      assay, and reverse transcription polymerase chain reaction, we determined the
      response to injury of a human bilayered skin substitute. Meshing or scalpel
      fenestration of the construct was found to stimulate keratinocyte migration and
      to decrease proliferation. By 24 h, flow cytometry of the keratinocyte component
      showed that meshing was associated with a 33% decrease in the number of cells in
      S phase (p < 0.01). An approximately 2-fold decrease in staining for Ki67, a
      proliferation marker, was observed with meshing of human bilayered skin
      substitute. The process of reepithelialization was apparent by 12 h, however, the
      wounded human bilayered skin substitute was healed by day 3, and a stratum
      corneum and fully stratified epithelium were re-established by day 4. Reverse
      transcription polymerase chain reaction analysis and enzyme-linked immunosorbent
      assays showed that the expression of acute proinflammatory cytokines
      (interleukins 1alpha, 6, and 8, tumor necrosis factor alpha) peaked by 12-24 h
      postinjury. The levels of mRNA of certain growth factors (transforming growth
      factor beta1, vascular endothelial growth factor, insulin-like growth factor 2)
      but not others (platelet-derived growth factors A and B, keratinocyte growth
      factor, fibroblast growth factors 1 and 7, transforming growth factor beta3)
      increased by 12 h and peaked by 1-3 d after injury, returning to normal by day 6.
      Immunostaining for tumor necrosis factor alpha and transforming growth factor
      beta1 paralleled these findings by reverse transcription polymerase chain
      reaction. We conclude that human bilayered skin substitute, as a prototypic
      bilayered skin substitute, is a truly dynamic living tissue, capable of
      responding to physical injury in a staged and specific pattern of cell migration,
      reepithelialization, and cytokine expression.

PMID- 12230510
TI  - Functional analysis of the profilaggrin N-terminal peptide: identification of
      domains that regulate nuclear and cytoplasmic distribution.
AB  - Profilaggrin is expressed in the differentiating granular layer of epidermis and
      other stratified epithelia, where it forms a major component of cytoplasmic
      keratohyalin granules. It consists of two distinct domains, an N-terminal S100
      like Ca2+- binding domain containing two EF-hands and multiple filaggrin units
      that aggregate keratin filaments in the stratum corneum. Here, we report
      structure-function studies of the N-terminal peptide from mouse, human, and rat
      profilaggrin. The profilaggrin N- terminal peptides of all species contain two
      S100-like EF-hands, bipartite nuclear localization sequences, and proprotein
      convertase cleavage sites. The nuclear localization signals in human and mouse
      profilaggrin were shown to be functional by transfection of epithelial cells and
      depended on the absence of filaggrin sequences. The nuclear localization of the
      processed (free) N-terminal peptide of human profilaggrin is consistent with
      immunolocalization findings in normal human skin and in parakeratotic skin
      disorders, which exhibit nuclear staining of granular and/or cornified layers.
      The mouse profilaggrin N-terminus undergoes proteolytic processing in two steps,
      first releasing an N-terminal peptide containing some filaggrin sequence and
      finally the free N-terminus of 28-30 kDa; these peptides have cytoplasmic and
      nuclear distributions, respectively, when expressed in transfected cells. The N
      terminal processing may occur prior to or simultaneously with the proteolytic
      processing of the polyfilaggrin domain. The nuclear accumulation of the
      profilaggrin N-terminal peptide in epidermis and in transfected cells strongly
      suggests a calcium-dependent nuclear function for the profilaggrin N-terminus
      during epidermal terminal differentia tion when the free N-terminus is released
      from profilaggrin by specific proteolysis.

PMID- 12230511
TI  - Expression of transglutaminase 5 in normal and pathologic human epidermis.
AB  - To explore the expression and gain more information on the function of
      transglutaminase 5 enzyme in normal and defective human epidermis, we generated a
      rat antihuman transglutaminase 5 antiserum elicited against a purified active
      recombinant protein expressed in the baculovirus system. By use of Western
      blotting and immunofluorescence methods, the immunospecificity of the antibodies
      for transglutaminase 5 was tested; no crossreactivity with other
      transglutaminases (types 1, 2, and 3) was observed, thus allowing histochemistry
      studies. By indirect immunofluorescence analysis the antibodies decorated the
      upper layers of normal human epidermis, with consistent staining in the spinous
      and granular layers. We evaluated transglutaminase 5 expression in comparison
      with proliferating (keratin 14) and differentiating (transglutaminase 3) markers
      in different diseases, such as psoriasis, ichthyosis vulgaris, lamellar
      ichthyosis, and Darier's disease. We observed that transglutaminase 5
      contributes, as a secondary effect, to the hyperkeratotic phenotype in ichthyosis
      (both vulgaris and lamellar) and in psoriasis. In Darier's disease,
      transglutaminase 5 expression, as well as transglutaminase 3, is completely
      missregulated, being overexpressed or totally absent in different areas of the
      same lesion.

PMID- 12230512
TI  - Targeted disruption of dermatopontin causes abnormal collagen fibrillogenesis.
AB  - Gene targeting of a member of small leucine-rich repeat proteoglycans
      demonstrates that collagen fibrillogenesis is mediated by a set of extracellular
      matrix components, which interact with collagen. Collagen-associated protein
      dermatopontin knockout mice were generated in order to analyze the biologic
      involvement of dermatopontin in the formation of collagen fibrils. Although
      dermatopontin-null mice did not exhibit any obvious anatomical abnormality, skin
      elasticity was increased. Skin tensile tests revealed that the initial elastic
      modulus was 57% lower in dermatopontin-null mice than in wild-type mice, and that
      maximum tensile strength was similar. Remarkably, light microscopy study showed a
      significant decrease in the relative thickness of the dermis in dermatopontin
      null mice compared with wild-type mice (45.2 +/- 3.09% and 57.8 +/- 4.25%,
      respectively). The skin collagen content was 40% lower in dermatopontin-null than
      in wild-type mice. Collagen fibrils in dermatopontin-null mice showed a great
      variety in diameter and irregular contours under the electron microscope. These
      data indicate that dermatopontin plays a critical role in elasticity of skin and
      collagen accumulation attributed to collagen fibrillogenesis in vivo.

PMID- 12230513
TI  - Animal models for skin blistering conditions: absence of laminin 5 causes
      hereditary junctional mechanobullous disease in the Belgian horse.
AB  - Recent achievements in the genetic correction of keratinocytes isolated from
      patients with junctional epidermolysis bullosa have paved the way to a gene
      therapy approach for the disease. Because gene therapy protocols require
      preclinical validation in animals, we have characterized spontaneous animal
      models of junctional epidermolysis bullosa. In this study we have elucidated the
      genetic basis of the hereditary junctional mechanobullous disease in the Belgian
      horse, a condition characterized by blistering of the skin and mouth epithelia,
      and exungulation (loss of the hoof). Immunofluorescence analysis associated the
      condition to the absent expression of the gamma2 chain of laminin 5 and
      designated Lamc2 as the candidate gene. Comparative analysis of the nucleotide
      sequence of the full-length gamma2 cDNA isolated by reverse transcription
      polymerase chain reaction amplification of total RNA purified from the epithelium
      of a junctional epidermolysis bullosa foal and a healthy control disclosed a
      homozygous basepair insertion (1368insC) in the affected animal. Mutation
      1368insC results in a downstream premature termination codon and is predicted to
      cause absent expression of the laminin gamma2 polypeptide. Our results also show
      that: (i) the horse junctional epidermolysis bullosa genetically corresponds to
      the severe Herlitz form of junctional epidermolysis bullosa in man; (ii) the
      amino acid sequence and structure of the horse laminin gamma2 chain are virtually
      identical to the human counterpart; (iii) the moderate eruption of skin blisters
      in the affected animals with respect to the human Herlitz junctional
      epidermolysis bullosa patients correlates with the protection provided by hair.
      Our observations suggest that the affected foals are a convenient source of
      epithelial cells from tissues that cannot be obtained from human junctional
      epidermolysis bullosa patients, and imply that hairless strains of animals with
      recessive skin disorders would be the best models for in vivo gene therapy
      approaches to skin blistering diseases.

PMID- 12230514
TI  - Refined mapping of Naegeli-Franceschetti- Jadassohn syndrome to a 6 cM interval
      on chromosome 17q11.2-q21 and investigation of candidate genes.
AB  - Naegeli-Franceschetti-Jadassohn syndrome and dermatopathia pigmentosa reticularis
      are autosomal dominant ectodermal dysplasias characterized by the absence of
      dermatoglyphics, reticulate hyper pigmentation of the skin, hypohidrosis, and
      heat intolerance. Palmoplantar keratoderma, nail dystrophy, and enamel defects
      are common in Naegeli-Franceschetti-Jadassohn syndrome, whereas diffuse alopecia
      is only seen in dermatopathia pigmentosa reticularis. We studied a large Swiss
      family with Naegeli-Franceschetti-Jadassohn syndrome originally described by
      Naegeli in 1927 and assessed linkage to chromosome 17q, which was proposed to
      harbor the Naegeli-Franceschetti-Jadassohn syndrome gene. Our results
      considerably narrow the Naegeli-Franceschetti-Jadassohn syndrome gene region from
      27 cM to 6 cM flanked by D17S933 and D17S934 with a maximum multipoint LOD score
      of 2.7 at marker locus D17S800. In addition, we studied a small family with
      dermatopathia pigmentosa reticularis, and our linkage data suggest that
      dermatopathia pigmentosa reticularis may map to the same chromosomal region. The
      Naegeli-Franceschetti-Jadassohn syndrome critical interval spans approximately
      5.4 Mb and contains a minimum of 45 distinct genes. We scrutinized 13 new prime
      candidates in addition to five genes previously examined, established the genomic
      organization of 10 of these genes, and excluded all of them by mutation analysis.
      Moreover, we identified a cDNA (KRT24) encoding a new keratin protein that bears
      high similarity to the type I keratins and displays a unique expression profile.
      No pathogenic mutations were identified in this novel gene either, however. In
      summary, our results substantially refine the Naegeli-Franceschetti-Jadassohn
      syndrome region and will aid in identifying a gene that is critical for
      ontogenesis of multiple ectodermal tissues.

PMID- 12230515
TI  - How fast are UV-dimers repaired in human skin DNA in situ?
AB  - Sheehan et al (2002) published a paper on UV-dimers in human skin and their
      repair with contradictions in their own data. In one experiment they applied two
      doses, 0.65 and 2 MED, but the apparent dimer levels, measured by a
      immunohistochemical technique, only increased in skin of type II (Fig 2a). The
      authors offered as explanation that the level of DNA damage would saturate. The
      dimer levels reached are at around 1 dimer per 1 million nucleotides, and there
      has been no evidence for saturation when a quantitative postlabeling technique
      has been used (Bykov et al, 1998). There is no reason for saturation until most
      of the thydmidyl-thymidine positions would be occupied in DNA, which, based on
      literature with other intrastrand cross-linkers, would require dimer levels 1 :
      100 (Forsti et al, 1989), or 10,000 times higher levels of dimer than that
      obtained by an irradiation at a MED dose.

PMID- 12230517
TI  - Human melanoma cell migration along capillary-like structures in vitro: a new
      dynamic model for studying extravascular migratory metastasis.

PMID- 12230518
TI  - Angiotropism in cutaneous melanoma: a prognostic factor strongly predicting risk
      for metastasis.

PMID- 12230519
TI  - Amifostine aminothiols and protection of keratinocyte apoptosis and DNA damage.

PMID- 12230520
TI  - Endogenous opiate alkaloids and human skin.

PMID- 12230523
TI  - The educational preparation of undergraduate nursing students in pharmacology: a
      survey of lecturers' perceptions and experiences.
AB  - BACKGROUND: Nurses have key responsibilities in the administration and management
      of medication therapy and client education. It is of some concern therefore that
      the literature indicates that nurses are inadequately prepared in this area.
      AIMS: This paper explores the perceptions and expectations of lecturers about
      teaching and learning pharmacology in preregistration nursing courses. RESEARCH
      METHODS: Questionnaires were distributed to lecturers involved in teaching
      pharmacology to undergraduate nursing students during 2000. The questionnaire was
      distributed to all university campuses (n = 13) in Victoria, Australia, that are
      involved in undergraduate nursing education. The questionnaire was an adaptation
      of the survey instrument used in the Nursing and Medication Education [NAME]
      project and examined in this questionnaire: the integration of pharmacology
      teaching into nursing, range and depth of classroom-based pharmacology teaching,
      approaches to teaching and learning, nursing practice in a clinical context,
      related importance of patient education and communication skills, and the
      appropriate professional background of academics teaching pharmacology to
      preregistration nursing students. RESULTS: There was great variation between
      institutions as to the number of hours devoted to pharmacology and when it was
      offered. A number of respondents indicated that they were dissatisfied with the
      preparation of graduates and their knowledge base in pharmacology. LIMITATIONS:
      The study was limited by a low response rate of 34%. CONCLUSIONS: A review of
      nursing curricula is required to improve the knowledge base of nurses in
      pharmacology and to facilitate their skills in life-long learning.

PMID- 12230524
TI  - Tobacco use and baccalaureate nursing students: a study of their attitudes,
      beliefs and personal behaviours.
AB  - AIM: To report findings about student nurses' attitudes, beliefs and personal
      behaviour in relation to tobacco issues. RATIONALE: Nurses have the potential to
      influence clients' behaviours and public policy concerning tobacco use. However,
      a review of the literature suggests that this is not happening. Further
      understanding of nursing students' attitudes, beliefs and behaviours regarding
      tobacco use is needed in order to develop strategies which can positively impact
      on their future health promotion role. METHODS: A cross-sectional survey of the
      total population of baccalaureate nursing students in one Canadian province was
      employed. Students were asked to complete a self-administered questionnaire,
      which included questions related to their smoking history; stage of behavioural
      change, and beliefs and attitudes towards tobacco. Students also completed the
      Health Promotion Lifestyle Profile (HPLP) and the Fagerstrom Nicotine Tolerance
      Scale. FINDINGS: Two hundred and seventy-two students (61.9%) responded. Sixty
      (22.1%) indicated that they smoked daily or in social situations. These smokers
      were found to have a fairly low level of nicotine dependence and although 91.4%
      said they wanted to quit, few were actively engaged in the quitting process
      (16.9%). When comparing the beliefs and attitudes of smoking and non-smoking
      students, proportionally more of the non-smokers agreed that smokers will need
      close family/friends to help them quit; that the health of society should be
      protected by laws against smoking; and that nurses should set a non-smoking
      example. Non-smokers indicated more health promoting behaviours on items in the
      HPLP especially on the variables of physical activity, nutrition and stress
      management. CONCLUSIONS: Nurses have the potential to influence clients'
      behaviours and public policy concerning tobacco use. Developing future nurses
      with the knowledge and skill to do so needs to be an important emphasis of
      nursing curricula.

PMID- 12230525
TI  - Caring as a slave morality: Nietzschean themes in nursing ethics.
AB  - BACKGROUND: Sceptical arguments about 'caring' can be divided into three
      categories. First, it is suggested that, while caring is no doubt an admirable
      thing in itself, it is just one ideal among others. Secondly, it is claimed that
      caring is not really a virtue at all, and that it should be regarded as more of a
      vice, because it promotes favouritism, injustice, and self-deception. Thirdly,
      there is a worry that caring is not politically realistic, and that its advocates
      underestimate the powerful organizational and social structures which conspire to
      subvert nursing. AIM: This paper outlines a fourth, and more radical, type of
      scepticism, which explains why caring is subject to these drawbacks. In doing so,
      it considers the relation between caring, phenomenology and holism in nursing
      discourse, and the way in which all three fit together to form the 'caring
      paradigm'. METHODS: The paper adopts a genealogical approach, borrowed directly
      from Nietzsche's Genealogy of Morality. That book argues that the values
      associated with caring are the expression of a profound resentment, harboured by
      the slaves (weak, powerless, timorous) against the nobles (strong, powerful, self
      confident). Caring represents an inversion, a sort of 'fantasy revenge', in which
      the nobles can be portrayed as 'evil', while the slaves portray their own
      weakness as 'good'. Taking its cue from Nietzsche, the paper shows that the
      Genealogy narrative can be transposed into a modern health care context, with
      nurses as the 'slaves' and the medical profession as the 'nobles'. CONCLUSIONS:
      The ideology of caring is, in the Genealogy's terms, a slave morality. It
      represents an attack on the 'medical-scientific model', motivated by resentment,
      and designed to establish nursing's superiority. Its effects have been
      debilitating, and it has prevented nursing from becoming a 'noble' (that is, a
      properly scientific) discipline.

PMID- 12230526
TI  - Edwards, Benner and Wrubel on caring.
AB  - AIMS: To explain the difficult Heideggerian concept of the ontological difference
      and then use it as a context to explain the misperceptions of Benner and Wrubel's
      reply to Edwards' criticism of the differences between ontological and
      intentional care. BACKGROUND: Edwards' paper attempts to clarify what Benner and
      Wrubel actually mean by the category of ontological care. The latter's reply
      totally bypasses Edwards' criticisms because they have a misunderstanding of
      Heidegger's philosophy, which they use to support their arguments. CONCLUSION:
      Benner and Wrubel's claims that they are using Heidegger to underpin their
      arguments is wrong. This has the consequence that their category of ontological
      caring comes tumbling down and their philosophy is not as radical as they think
      it is.

PMID- 12230529
TI  - The nursing contribution to qualitative research in palliative care 1990-1999: a
      critical evaluation.
AB  - BACKGROUND: Qualitative research plays an important part in providing evidence
      for practice in nursing, and is gaining greater acceptance within medicine.
      However, questions remain about what criteria are most appropriate for evaluating
      qualitative research. To date, little systematic evaluation of qualitative
      research in palliative care has been conducted. AIMS: This paper is based on a
      larger study in which we conducted a critical review of qualitative research in
      palliative care from nursing, medicine, specialist palliative care, sociology,
      death studies, medical anthropology, and gerontology journals published between
      1990 and 1999. The aim of this paper is to present an account of the strengths
      and weaknesses of qualitative palliative care research in nursing, using data
      from this review. METHODS: In the larger study, 138 papers from 50 journals were
      reviewed critically using a tool developed to assess both content and quality; in
      one part of this tool reviewers recorded open-ended comments on the strengths and
      weaknesses of each paper. In this paper, we present a thematic analysis of
      reviewers' comments on a subgroup of 67 nursing papers from the main review,
      together with an analysis of comments on 29 papers from a comparison group of
      death studies, medical anthropology, and sociology journals. Patterns of positive
      and negative evaluation are identified and used to generate an account of
      strengths and weaknesses in qualitative palliative care research in nursing.
      FINDINGS: Over 40% of the subgroup of papers from nursing journals received
      positive comments on topic and quality of writing; around 30% received positive
      comments on contribution to understanding, practical value, and conceptual or
      theoretical issues. Less than 20% received positive comments on other critical
      dimensions. Over 40% of nursing papers received negative comments on the link
      between data, analysis, and findings, other aspects of method and theoretical and
      conceptual issues. A higher proportion of papers in the comparison group received
      positive comments on conceptual and theoretical issues and contribution to
      understanding. CONCLUSIONS: Nearly half the nursing papers reviewed were judged
      to be well written or to have a well-chosen topic. However, more than 40% of
      papers drew negative comments about key methods-related issues. Arguably
      therefore efforts to improve the quality of research evidence should focus on
      this area.

PMID- 12230530
TI  - Gaining access to the life-world of women suffering from stroke: methodological
      issues in empirical phenomenological studies.
AB  - AIM: First to give a brief introduction to some dimensions of phenomenology as
      philosophy, and then to discuss some problems related to empirical research. The
      objectives of the discussion are: (1) to show what is involved in investigating
      changes in the life-world caused by illness and (2) to show what must be taken
      into consideration to obtain adequate descriptions of the changes. RATIONALE: To
      discuss some of the methodological requirements and challenges that
      phenomenological studies are expected to meet, particularly focusing on the data
      collection phase. METHODS: This is primarily a theoretical analysis supplemented
      by illustrations drawn from an ongoing study of women who have had suffered
      stroke. FINDINGS: Openness is essential in the whole research process. It is a
      precondition for conversation with the informants. In interview-based
      investigations two forms of openness are at issue - the informant's openness in
      describing his/her life-world, and the sensitivity of the researcher as regards
      seeing and hearing what is conveyed in the situation. Both forms of openness can
      be influenced positively or negatively by many factors, including the physical
      and mental health of the informants, the researcher's theoretical insight, her
      ability to communicate, and not least the relationship between the informant and
      the researcher. A relationship of power, for example, might reinforce gender
      differences, differences in cultural background, education and social status.
      CONCLUSION: Openness on the part of the researcher is a prerequisite in order to
      gain access to the informant's life-world.

PMID- 12230531
TI  - Developing an understanding of gender sensitive care: exploring concepts and
      knowledge.
AB  - BACKGROUND: In the United Kingdom (UK), concern about inequalities in health and
      health care has led to interest in gender sensitivity in health policy and
      practice. AIM: To develop an understanding of possibilities for gender sensitive
      care through exploring the concepts of gender and gender sensitivity and through
      reviewing relevant knowledge about gender and health. METHODS: The dimensions of
      the concept of gender and theories explaining gender relations are explored
      through a review of key social science texts. A discussion of gender sensitivity
      draws on Bowden's analysis of gender sensitive ethics. A literature review of
      evidence about gender and health identifies relevant knowledge for gender
      sensitive care. FINDINGS: Seven features of the concept of gender are identified.
      Gender sensitivity involves an understanding of the socio-political context of
      experience and relationships. The social context also affects health. Differences
      in male and female mortality and morbidity rates are likely to be related to
      differences in economic resources, differences in men and women's position in
      public and private worlds, to power in social relations and to sexuality and body
      image. Possibilities for gender sensitive care may be supported through feminist
      approaches and through a postmodernist understanding of the manner in which
      discourses shape our understanding of gender and gender relations. Valuing care
      is a feature of gender sensitivity. CONCLUSION: Gender sensitive care involves
      recognizing the significance of research related to social influences on health
      and understanding nursing in its socio-political context, and care in the context
      of gender relations. Experiential learning can synthesize learning across varied
      learning modes, bridging learning through experience and formal analysis.
      Exploring concepts, evidence about gender and health and personal experience will
      all be important in the development of gender sensitive care.

PMID- 12230532
TI  - Poor communication and knowledge deficits: obstacles to effective management of
      children's postoperative pain.
AB  - AIM OF THE STUDY: To explore the perceptions of nurses and parents of the
      management of postoperative pain in children. This paper focuses on issues of
      knowledge and communication. BACKGROUND: Nurses are the key health care
      professionals with responsibility for managing children's pain, however, nurses
      are not well supported educationally to manage the level of responsibility.
      RESULTS: Using matched interviews between 20 parents and 20 nurses many issues
      arose relating to the nurse/parent communication process. It was also clear that
      despite nurses' knowledge of pain management being deficient, they had
      expectations that required parents to have a level of knowledge they did not
      possess. CONCLUSIONS: The findings suggest that nurses' poor communication with
      parents and nurses' knowledge deficits in relation to children's pain management
      create obstacles to effective pain management. These obstacles need to be
      addressed in order to improve the management of children's pain through better
      education of nurses and two way communication with parents.

PMID- 12230533
TI  - Men living with fibromyalgia-type pain: experiences as patients in the Swedish
      health care system.
AB  - BACKGROUND: Individuals with fibromyalgia (FM) frequently use health care
      services and experience only short-term improvements. They often feel that health
      care staff do not take them seriously. This increases the burden of living with
      the illness. AIM: To describe how men living with fibromyalgia-type pain
      experienced being patients in the Swedish health care system. METHOD: Narrative
      interviews with 14 men who fulfilled the American College of Rheumatology
      criteria for classification of fibromyalgia. Content analysis was used when
      analysing the data. RESULTS: The results are described using five themes. Theme I
      'Feeling afraid of being looked upon as being a whiner' highlights how the men
      endured a lot of pain before they sought health care, and how difficult it was to
      find a receptive listener. Theme 2 'Feeling like a guinea pig' shows that the
      men's feelings were twofold; they wanted examinations, even if these made them
      feel that they were being exposed to numerous treatments without any cure. Theme
      3 'Feeling hopeful' describes the hope for a cure after having been referred to a
      specialist clinic. Theme 4 'Feeling neglected' illustrates being looked upon as
      an uninteresting patient and theme 5 'Feeling no recovery' illustrates the pain
      relief they gained, but not the actual cure. CONCLUSION: Men with FM type pain
      experienced a long wait before treatment at a specialist clinic as well as no
      continuity and follow-ups in primary care and general hospitals. Encounters with
      engaged and skilful staff promoted the men's well-being despite the fact that no
      cure was available. Not being respected led to a feeling of being neglected
      despite the care received. Thus, the men had to accept the fact that they would
      never recover.

PMID- 12230534
TI  - Unmet nursing care needs of home-based disabled patients.
AB  - BACKGROUND: In Taiwan, family members care for 80-90% of disabled people, but
      most have no professional training or knowledge of care for the disabled.
      Therefore, the adequacy of care received by the disabled needs to be assessed.
      AIMS: To evaluate the unmet nursing care needs of physically disabled patients
      and determine the relevant factors. METHODS: All 322 subjects were over 18 years
      of age, had a Barthel Index of less than 80 and became disabled 2 years prior to
      the commencement of this study. All subjects were outpatients of hospitals in
      central Taiwan and were contacted by phone to schedule an interview. Based on
      activity of daily living (ADL) scores, patients were divided into three groups:
      complete dependency, severe dependency and moderate dependency. After training,
      nurses evaluated the patients' ADL and completed the 20-item Assessment of
      Nursing Activity (ANA) questionnaire. Based on the ANA, subjects' unmet needs and
      caregivers' knowledge requirements were assessed. FINDINGS: The results showed
      the mean number of unmet needs was approximately five. Percentage of unmet needs
      was 44.8%. For complete dependency patients, the unmet needs score of patients
      and the needs score of caregiver's knowledge was highest, followed by the severe
      dependency group, and the moderate dependency group. Based on multiple linear
      regression, the factors that affected unmet need were as follows: age of patient,
      ADL score, education level of the caregivers, average daily duration of care and
      need of caregiving knowledge. Our findings indicate that the provision of
      counseling and educational support for family caregivers is required to promote
      quality of care for the disabled.

PMID- 12230535
TI  - Can staff attitudes to team working in stroke care be improved?
AB  - BACKGROUND: Teamwork is regarded as the cornerstone of rehabilitation. It is
      recognized that the skills of a multiprofessional team are required to provide
      the care and interventions necessary to maximize the patient's potential to
      recover from his/her stroke. LITERATURE REVIEW: Critical evaluation of team
      working is lacking in the literature. Indeed, there is no consensus on a precise
      definition of teamwork or on the best way of implementing it, beyond a general
      exhortation to members to work to the same therapeutic plan in a cohesive manner.
      The literature has highlighted many problems in team working, including petty
      jealousies, ignorance and a perceived loss of autonomy and threat to professional
      status. AIM: To determine if the use of team co-ordinated approaches to stroke
      care and rehabilitation would improve staff attitudes to team working. METHOD: A
      pre-post design was adopted using 'The Team Climate Inventory' to explore
      attitudes to team working before and after introducing the interventions. Local
      Research Ethics Committee approval was obtained. RESULTS: Improvements in
      attitudes towards team working suggest that the introduction of team co-ordinated
      approaches (integrated care pathways and team notes) did not result in greater
      team working. LIMITATIONS: The introduction of an integrated care pathway and
      team notes is based on an assumption that they would enhance team working.
      CONCLUSIONS: The results suggest that the introduction of team co-ordinated
      approaches (team notes and care pathways) do not improve attitudes to team
      working, teams appear to take a long time to establish cohesion and develop
      shared values.

PMID- 12230536
TI  - Living with newly diagnosed breast cancer: a qualitative study of 10 women with
      newly diagnosed breast cancer.
AB  - AIM: The aim of this qualitative study was to describe from the perspective of 10
      women (aged 39-69 years), their experience of living with breast cancer.
      BACKGROUND: Although there is increasing research into a variety of aspects
      associated with breast cancer, there is a continuing need for research to
      increase nurses' understanding of how women experience living with newly
      diagnosed breast cancer. DESIGN/METHODS: Following ethical approval, open-ended
      interviews were analysed, using methods influenced by Grounded Theory.
      Verifiability and empirical grounding of the theory was established through use
      of the constant comparative method. FINDINGS: Existential issues arose as an
      important aspect of living with newly diagnosed breast cancer. The will to live
      emerged as the central theme. All energy was channelled into a tenacious fight
      for life. Furthermore, results revealed other aspects in the women's awareness of
      living with breast cancer, such as their experiences in relation to emotional
      reactions, bodily physical changes, their female identity, meaningful activities
      and their social network. CONCLUSIONS: An understanding of how women experience
      their new and changed life situation is important to the support nurses give in
      the process of healing. Nurses need this knowledge to be better able to assist
      women and their families in their development of coping strategies.

PMID- 12230538
TI  - Population variability in Chironomus (Camptochironomus) species (Diptera,
      Nematocera) with a Holarctic distribution: evidence of mitochondrial gene flow.
AB  - Phylogenetic analysis of DNA sequences from mitochondrial (mt) genes (Cytochrome
      b and Cytochrome oxidase I) and one nuclear gene (globin 2b) was used for the
      investigation of Nearctic and Palearctic populations representing four Chironomus
      species of the subgenus Camptochironomus, namely C. biwaprimus, C.
      pallidivittatus, C. tentans sensu stricto and C. dilutus (the last two species
      constitute Holarctic C. tentans sensu lato). Phenograms constructed on the basis
      of mt sequences were not congruent with trees based on nuclear genes, or with
      morphological and cytological data. The mt tree divided the populations by
      continental region, rather than by the species groupings recognized by the other
      data sets. The incongruence is explained by mt gene flow resulting from
      hybridization between the sympatric species on each continent. Calculation of
      divergence times, based on the sequence data, suggest that C. tentans (s.l.) and
      C. pallidivittatus have both been in North America for about 2.5 My.

PMID- 12230539
TI  - Transgene expression from the Tribolium castaneum Polyubiquitin promoter.
AB  - The highly conserved Ubiquitin proteins are expressed from genes with strong,
      constitutively active promoters in many species, making these promoters
      attractive candidates for use in driving transgene expression. Here we report the
      cloning and characterization of the Tribolium castaneum Polyubiquitin (TcPUb)
      gene. We placed the TcPUb promoter upstream of the coding region of the T.
      castaneum eye-colour gene Tc vermilion (Tcv) and injected this construct into
      embryos from a Tcv-deficient strain. Transient expression of Tcv during
      embryogenesis resulted in complete rescue of the larval mutant phenotype. We then
      incorporated the TcPUb-Tcv chimera into a piggyBac donor. Resulting germline
      transformants were easily recognized by rescue of eye pigmentation, illustrating
      the potential of the TcPUb promoter for use in driving transgene expression.

PMID- 12230540
TI  - Molecular analysis of multiple cytochrome P450 genes from the malaria vector,
      Anopheles gambiae.
AB  - Cytochrome P450s are a superfamily of haemoproteins, important in the metabolism
      of endogenous compounds and xenobiotics. As a first step to elucidating the role
      of this family in insecticide resistance in the malaria mosquito, Anopheles
      gambiae, we have cloned and mapped multiple P450 genes. Sixteen cDNAs encoding
      full-length P450s were cloned and physically mapped to the mosquito's polytene
      chromosomes. Fourteen of these encode putative CYP6 proteins and two encode P450s
      belonging to the CYP9 class. Eighteen new A. gambiae Cyp4 P450 genes were
      identified using degenerate PCR primers, cDNAs were detected for ten and in situ
      locations for thirteen members of this gene family.

PMID- 12230541
TI  - The period gene in two species of tephritid fruit fly differentiated by mating
      behaviour.
AB  - The period gene is important for the generation and maintenance of biological
      rhythms. It served as an ideal candidate for the investigation of the mating time
      isolation between two sibling Queensland fruit fly species, Bactrocera tryoni and
      Bactrocera neohumeralis. We have isolated the homologues of the period gene in
      the two species, and show that their putative amino acid sequences are identical.
      No length polymorphism was detected in the Thr-Gly repeat region. per mRNA
      expression, assayed in light-dark diurnal conditions, displayed circadian
      oscillation in both the head and abdomen of B. tryoni and B. neohumeralis, with
      the same cycling phase. An alternatively spliced intron was identified in the 3'
      untranslated region. The effect of temperature on the splicing and mRNA
      expression was examined.

PMID- 12230542
TI  - Developmental- and tissue-specific expression of an inhibitor of apoptosis
      protein 1 homologue from Aedes triseriatus mosquitoes.
AB  - We have identified a homologue of the Drosophila inhibitor of apoptosis protein 1
      in Aedes triseriatus mosquitoes (designated AtIAP1). The AtIAP1 gene maps to a
      single locus on chromosome 2. The translation product is a 403 amino acid protein
      that contains two baculovirus IAP repeat (BIR) domains and a RING finger motif.
      AtIAP1 mRNA was detectable by RT-PCR amplification in all the mosquito
      developmental stages (embryos, first-fourth instar larvae, early and late pupae,
      adults) and adult tissues (midguts, ovaries) examined. In contrast, immunoblots
      with AtIAP1-specific antibodies revealed that the protein was detectable only in
      certain developmental stages (first instar larvae, early pupae, adults) and
      tissues (ovaries). AtIAP1-specific serum also recognized proteins in Ae. aegypti,
      Ae. albopictus and Culex tritaeniorhynchus. Immunoblot analysis revealed that
      similar amounts of IAP1 were expressed in LaCrosse virus infected and uninfected
      Ae. albopictus cell cultures.

PMID- 12230543
TI  - Linkage analysis of maternal EST cDNA clones covering all twenty-eight
      chromosomes in the silkworm, Bombyx mori.
AB  - A cDNA library of maternal messages was constructed from non-fertilized Bombyx
      mori eggs collected just after oviposition without mating. cDNA clones were
      identified by their nucleotide sequences and evaluated as probes for RFLP linkage
      analysis. Back crossed F1 segregants - by crossing an F1 female (RF02 x RF50) and
      a male (RF02) - were used, which takes advantage of the phenomenon that no
      crossing over occurs in Bombyx females. Fifteen ordered BF1 segregants gave
      either homozygous (homo) or heterozygous (hetero) RFLP patterns with each cDNA
      probe. cDNA probes on the same linkage group gave the same homo/hetero order. One
      hundred and fifty one out of 248 cDNA clones showed polymorphisms between RF02
      and RF50, and were therefore suitable as probes for RFLP linkage analysis in the
      present BF1 cross. They were sorted into twenty-seven linkage groups and one
      independent group, by the homo/hetero pattern matrix, covering all twenty-eight
      chromosomes in B. mori.

PMID- 12230544
TI  - Elongation Factor 1 alpha resolves the monophyly of the haplodiploid ambrosia
      beetles Xyleborini (Coleoptera: Curculionidae).
AB  - Elongation Factor 1-alpha was used to test the monophyly of the wood boring
      beetle tribe Xyleborini, where all species are haplodiploid and perform regular
      inbreeding by brother-sister mating. Due to their feeding requirements, being
      highly dependent on ophiostomatoid fungi which they cultivate in wood tunnels,
      monophyly may be expected due to nutritional constraints. During the course of
      analyses, two copies of EF-1alpha were amplified in these beetles, differing in
      intron structure. The high similarity between paralogous amino acid sequences (93
      94%) indicates a rather recent duplication in beetles, but phylogenetic analyses
      of different copies in insects rejected this hypothesis. Subsequent phylogenetic
      analyses of eighty orthologous sequences from Xyleborini and allied taxa, using
      the single-intron bearing copy, were greatly improved in resolution and node
      support by including the intron sequences (c. 60 bp). Most analyses resulted in a
      monophyletic Xyleborini, implying one origin of fungus feeding in this tribe.
      However, clear evidence for a polyphyletic Xyleborus and three more xyleborine
      genera calls for further revision of xyleborine classification.

PMID- 12230546
TI  - Isolation and characterization of a neprilysin-like protein from Venturia
      canescens virus-like particles.
AB  - Maternal protein secretions from endoparasitoid wasps are evolutionary
      adaptations to regulate host physiology as part of an extended wasp phenotype.
      Virus-like particles (VLPs) produced in the calyx region of Venturia canescens
      wasps are involved in immune evasion of the developing parasitoid inside the
      host. In contrast to polydnaviruses (PDVs), VcVLPs are devoid of any nucleic
      acids. To understand the role of these particles in the regulation of host
      physiology and phylogenetic relationship between VLPs and PDVs, it is essential
      to identify particle proteins. In this paper, we describe the isolation and
      molecular cloning of a neprilysin-like gene (VcNEP) coding for a 94 kDa VcVLP
      protein and discuss its possible role in host regulation.

PMID- 12230547
TI  - Drosophila yolk protein produced in E. coli is accumulated by mosquito ovaries.
AB  - Despite similar functions, the yolk proteins of the higher dipteran flies and the
      vitellogenins found in other insects are unrelated at the sequence level and have
      evolved from different genes. Both are selectively endocytosed into the ovary via
      receptors belonging to the LDLR receptor subfamily. We cloned the Drosophila yp1
      gene into an E. coli expression vector and showed that the yolk protein produced
      by E. coli is taken up into ovaries of both Drosophila melanogaster and the
      malaria mosquito Anopheles gambiae, which normally uses vitellogenin.

PMID- 12230548
TI  - cDNA cloning, functional expression and characterization of kynurenine 3
      hydroxylase of Anopheles stephensi (Diptera: Culicidae).
AB  - Kynurenine 3-hydroxylase (K3H) is a NADPH-dependent flavin monooxygenase involved
      in the tryptophan pathway. Xanthurenic acid (XA) is a metabolite of this pathway
      and has recently been identified as a gamete activating factor (GAF) of the
      malarial parasite. We cloned K3H cDNA from Anopheles stephensi (AsK3H), because
      anopheline mosquitoes are a vector of the human malaria parasite, Plasmodium
      falciparum and the catalytic function of AsK3H in XA production. Recombinant
      AsK3H protein was expressed in Sf-9 cells using the baculovirus system and its
      enzymatic properties were characterized. The specific activities of crude cell
      lysate and affinity purified protein were 94.9 +/- 6.2 and 865.6 +/- 10.5
      nmol/min/mg protein, respectively. The optimum pH of AsK3H was 7.0. Analysis of
      AsK3H gene expression using RT-PCR revealed that AsK3H was constitutively
      expressed in egg, larva, pupa and adult.

PMID- 12230549
TI  - An intron enhancer activates the immunoglobulin-related Hemolin gene in
      Hyalophora cecropia.
AB  - Hemolin is the only insect member of the immunoglobulin (Ig) superfamily reported
      to be up-regulated during an immune response. In diapausing pupae of Hyalophora
      cecropia the gene is expressed in fat body cells and in haemocytes. Like the
      mammalian Ig kappa light chain gene, the Hemolin gene harbours an enhancer
      including a kappaB motif in one of its introns. This motif binds the H. cecropia
      Rel factor Cif (Cecropia immunoresponsive factor). The Hemolin third intron also
      mediates transient reporter gene expression in immunoresponsive Drosophila mbn-2
      cells. Co-transfections of Drosophila SL2 cells showed that the Drosophila Rel
      factor Dif (Dorsal-related immunity factor), transactivates reporter gene
      constructs through the intron. Moreover, a 4.8-fold synergistic activation was
      obtained when Dif is combined with the rat C/EBP (CCAAT/enhancer element-binding
      protein) and human HMGI (high mobility group protein I). This is the first report
      of an insect immune-related gene that is up-regulated by an enhancer activity
      conferred through an intron.

PMID- 12230550
TI  - Identification of microsomal rat liver carboxylesterases and their activity with
      retinyl palmitate.
AB  - Retinyl esters are a major endogenous storage source of vitamin A in vertebrates
      and their hydrolysis to retinol is a key step in the regulation of the supply of
      retinoids to all tissues. Some members of nonspecific carboxylesterase family (EC
      3.1.1.1) have been shown to hydrolyze retinyl esters. However, the number of
      different isoenzymes that are expressed in the liver and their retinyl palmitate
      hydrolase activity is not known. Six different carboxylesterases were identified
      and purified from rat liver microsomal extracts. Each isoenzyme was identified by
      mass spectrometry of its tryptic peptides. In addition to previously
      characterized rat liver carboxylesterases ES10, ES4, ES3, the protein products
      for two cloned genes, AB010635 and D50580 (GenBank accession numbers), were also
      identified. The sixth isoenzyme was a novel carboxylesterase and its complete
      cDNA was cloned and sequenced (AY034877). Three isoenzymes, ES10, ES4 and ES3,
      account for more than 95% of rat liver microsomal carboxylesterase activity. They
      obey Michaelis-Menten kinetics for hydrolysis of retinyl palmitate with Km values
      of about 1 micro m and specific activities between 3 and 8 nmol.min-1.mg-1
      protein. D50580 and AY034877 also hydrolyzed retinyl palmitate. Gene-specific
      oligonucleotide probing of multiple-tissue Northern blot indicates differential
      expression in various tissues. Multiple genes are highly expressed in liver and
      small intestine, important tissues for retinoid metabolism. The level of
      expression of any one of the six different carboxylesterase isoenzymes will
      regulate the metabolism of retinyl palmitate in specific rat cells and tissues.

PMID- 12230551
TI  - Metabolic control in integrated biochemical systems.
AB  - Traditional analyses of the control and regulation of steady-state concentrations
      and fluxes assume the activities of the enzymes to be constant. In living cells,
      a hierarchical control structure connects metabolic pathways to signal
      transduction and gene-expression. Consequently, enzyme activities are not
      generally constant. This would seem to compromise analyses of control and
      regulation at the metabolic level. Here, we investigate the concept of metabolic
      quasi-steady state kinetics as a means of applying metabolic control analysis to
      hierarchical biochemical systems. We discuss four methods that enable the
      experimental determination of metabolic control coefficients, and demonstrate
      these by computer simulations. The best method requires extra measurement of
      enzyme activities, two others are simpler but are less accurate and one method is
      bound only to work under special conditions. Our results may assist in evaluating
      the relative importance of transcriptomics and metabolomics for functional
      genomics.

PMID- 12230545
TI  - Comparison of EST libraries from seven beetle species: towards a framework for
      phylogenomics of the Coleoptera.
AB  - Relatively little is known about Coleoptera genes and genomes and how these
      compare in different taxa. We describe here the construction, DNA sequencing and
      sequence comparisons of cDNA libraries from seven beetle species. A total of 6717
      bacterial colonies were screened for cDNA insert containing plasmids and 2784
      size selected clones were 5'- and 3'-end sequenced to produce 1620 assembled
      sequences. Similarity comparisons with existing protein sequence databases
      revealed that 65.1% had matches (E < 10(-4)) in other organisms, with greater
      numbers of matches in Drosophila melanogaster than Caenorhabditis elegans and
      Saccharomyces cerevisiae databases. tBlastX comparisons also revealed numerous
      similarity hits (E < 10(-20)) in intra- and interlibrary comparisons. These
      results show the potential of small cDNA libraries for discovery and comparative
      analysis of genes useful for phylogenomic and functional studies.

PMID- 12230552
TI  - Short-chain dehydrogenases/reductases (SDRs).
AB  - Short-chain dehydrogenases/reductases (SDRs) are enzymes of great functional
      diversity. Even at sequence identities of typically only 15-30%, specific
      sequence motifs are detectable, reflecting common folding patterns. We have
      developed a functional assignment scheme based on these motifs and we find five
      families. Two of these families were known previously and are called 'classical'
      and 'extended' families, but they are now distinguished at a further level based
      on coenzyme specificities. This analysis gives seven subfamilies of classical
      SDRs and three subfamilies of extended SDRs. We find that NADP(H) is the
      preferred coenzyme among most classical SDRs, while NAD(H) is that preferred
      among most extended SDRs. Three families are novel entities, denoted
      'intermediate', 'divergent' and 'complex', encompassing short-chain alcohol
      dehydrogenases, enoyl reductases and multifunctional enzymes, respectively. The
      assignment scheme was applied to the genomes of human, mouse, Drosophila
      melanogaster, Caenorhabditis elegans, Arabidopsis thaliana and Saccharomyces
      cerevisiae. In the animal genomes, the extended SDRs amount to around one quarter
      or less of the total number of SDRs, while in the A. thaliana and S. cerevisiae
      genomes, the extended members constitute about 40% of the SDR forms. The numbers
      of NAD(H)-dependent and NADP(H)-dependent SDRs are similar in human, mouse and
      plant, while the proportions of NAD(H)-dependent enzymes are much lower in fruit
      fly, worm and yeast. We show that, in spite of the great diversity of the SDR
      superfamily, the primary structure alone can be used for functional assignments
      and for predictions of coenzyme preference.

PMID- 12230553
TI  - Elucidation of the role of fructose 2,6-bisphosphate in the regulation of glucose
      fluxes in mice using in vivo (13)C NMR measurements of hepatic carbohydrate
      metabolism.
AB  - Fructose 2,6-bisphosphate (Fru-2,6-P2) plays an important role in the regulation
      of major carbohydrate fluxes as both allosteric activator and inhibitor of target
      enzymes. To examine the role of Fru-2,6-P2 in the regulation of hepatic
      carbohydrate metabolism in vivo, Fru-2,6-P2 levels were elevated in ADM mice with
      adenovirus-mediated overexpression of a double mutant bifunctional enzyme, 6
      phosphofructo-2-kinase/fructose-2,6-bisphosphatase (n = 6), in comparison to
      normal control mice (control, n = 6). The rates of hepatic glycogen synthesis in
      the ADM and control mouse liver in vivo were measured using new advances in 13C
      NMR including 3D localization in conjunction with [1-13C]glucose infusion. In
      addition to glycogen C1, the C6 and C2-C5 signals were measured simultaneously
      for the first time in vivo, which provide the basis for the estimation of direct
      and indirect synthesis of glycogen in the liver. The rate of label incorporation
      into glycogen C1 was not different between the control and ADM group, whereas the
      rate of label incorporation into glycogen C6 signals was in the ADM group 5.6 +/-
      0.5 micro mol.g-1.h-1, which was higher than that of the control group of 3.7 +/-
      0.5 micro mol.g-1.h-1 (P < 0.02). The rates of net glycogen synthesis, determined
      by the glycogen C2-C5 signal changes, were twofold higher in the ADM group (P =
      0.04). The results provide direct in vivo evidence that the effects of elevated
      Fru-2,6-P2 levels in the liver include increased glycogen storage through
      indirect synthesis of glycogen. These observations provide a key to understanding
      the mechanisms by which elevated hepatic Fru-2,6-P2 levels promote reduced
      hepatic glucose production and lower blood glucose in diabetes mellitus.

PMID- 12230554
TI  - A peptide derived from cyclin-dependent kinase activator (p35) specifically
      inhibits Cdk5 activity and phosphorylation of tau protein in transfected cells.
AB  - Cyclin-dependent kinase-5 (Cdk5) is a serine/threonine kinase activated by its
      neuron-specific activator, p35, or its truncated form, p25. It has been proposed
      that the deregulation of Cdk5 activity by association with p25 in human brain
      tissue disrupts the neuronal cytoskeleton and may be involved in
      neurodegenerative diseases such as Alzheimer's disease. In this study, we
      demonstrate that a short peptide (amino acid residues 154-279; Cdk5 inhibitory
      peptide; CIP), derived from p35, specifically inhibits Cdk5 activity in vitro and
      in HEK293 cells cotransfected with the peptide and Cdk5/p25, but had no effect on
      endogenous cdc2 kinase activity. Moreover, we demonstrate that the
      phosphorylation of tau in HEK293 cells, cotransfected with Cdk5/p25 and CIP, is
      effectively reduced. These results suggest that CIP specifically inhibits both
      Cdk5/p25 complex activity and the tau hyperphosphorylation induced by Cdk5/p25.
      The elucidation of the molecular basis of p25 activation and CIP inhibition of
      Cdk5 activity may provide insight into mechanisms underlying the pathology of
      Alzheimer's disease and contribute to therapeutic strategies.

PMID- 12230555
TI  - The soluble form of the membrane-bound transferrin homologue, melanotransferrin,
      inefficiently donates iron to cells via nonspecific internalization and
      degradation of the protein.
AB  - Melanotransferrin (MTf) is a membrane-bound transferrin (Tf) homologue found
      particularly in melanoma cells. Apart from membrane-bound MTf, a soluble form of
      the molecule (sMTf) has been identified in vitro[Food, M.R., Rothenberger, S.,
      Gabathuler, R., Haidl, I.D., Reid, G. & Jefferies, W.A. (1994) J. Biol. Chem.269,
      3034-3040] and in vivo in Alzheimer's disease. However, nothing is known about
      the function of sMTf or its role in Fe uptake. In this study, sMTf labelled with
      59Fe and 125I was used to examine its ability to donate 59Fe to SK-Mel-28
      melanoma cells and other cell types. sMTf donated 59Fe to cells at 14% of the
      rate of Tf. Analysis of sMTf binding showed that unlike Tf, sMTf did not bind to
      a saturable Tf-binding site. Studies with Chinese hamster ovary cells with and
      without specific Tf receptors showed that unlike Tf, sMTf did not donate its 59Fe
      via these pathways. This was confirmed by experiments using lysosomotropic agents
      that markedly reduced 59Fe uptake from Tf, but had far less effect on 59Fe uptake
      from sMTf. In addition, an excess of 56Fe-labelled Tf or sMTf had no effect on
      125I-labelled sMTf uptake, suggesting a nonspecific interaction of sMTf with
      cells. Protein-free 125I determinations demonstrated that in contrast with Tf,
      sMTf was markedly degraded. We suggest that unlike the binding of Tf to specific
      receptors, sMTf was donating Fe to cells via an inefficient mechanism involving
      nonspecific internalization and subsequent degradation.

PMID- 12230556
TI  - Isoprenoid biosynthesis via the methylerythritol phosphate pathway. Mechanistic
      investigations of the 1-deoxy-D-xylulose 5-phosphate reductoisomerase.
AB  - The 1-deoxyxylulose 5-phosphate reductoisomerase (DXR, EC 1.1.1.267) catalyzes
      the conversion of 1-deoxy-d-xylulose 5-phosphate (DXP) into 2-C-methyl-d
      erythritol 4-phosphate (MEP). This transformation is a two-step process involving
      a rearrangement of DXP into the putative intermediate 2-C-methyl-d-erythrose 4
      phosphate followed by a NADPH-dependent reduction of the latter aldehyde. By
      using [1-(13)C]DXP as a substrate, the rearrangement of DXP into [5-(13)C]2-C
      methyl-d-erythrose 4-phosphate was shown to be NADPH dependent, although it does
      not involve areduction step. The putative aldehyde intermediate, obtained by
      chemical synthesis, was converted into MEP by the DXR in the presence of NADPH
      and into DXP in the presence of NADP(+), indicating the reversibility of the
      reaction catalyzed by the DXR. This reversibility was confirmed by the conversion
      of MEP into DXP in the presence of NADP(+). The equilibrium was, however, largely
      displaced in favour of the formation of MEP. The reduction step required the
      presence of a divalent cation such as Mg(2+) or Mn(2+).

PMID- 12230557
TI  - Altering the surface properties of baculovirus Autographa californica NPV by
      insertional mutagenesis of the envelope protein gp64.
AB  - The envelope protein gp64 of the baculovirus Autographa californica nuclear
      polyhedrosis virus is essential for viral entry into insect cells, as the
      glycoprotein both mediates pH-dependent membrane fusion and binds to host cell
      receptors. Surface modification of baculovirus particles by genetic engineering
      of gp64 has been demonstrated by various strategies and thus has become an
      important and powerful tool in molecular biology. To improve further the
      presentation of peptides on the surface of baculovirus particles, several
      insertion sites within the gp64 envelope protein were selected by their
      theoretical maximum surface probability and investigated for efficient peptide
      presentation. The ELDKWA peptide of the gp41 of HIV-1, specific for the human mAb
      2F5, was inserted into 17 different positions of the glycoprotein gp64.
      Propagation of viruses was successful in 13 cases, mutagenesis at four positions
      did not result in production of intact virus particles. Western blotting, FACS
      analysis and ELISA were used for characterization of the different binding
      properties of the mutants. Insertion of this peptide into the native envelope
      protein resulted in high avidity display on the surface of baculovirus particles.
      This approach offers the possibility of effective modification of surface
      properties in regard to host range specificity and antigen display.

PMID- 12230559
TI  - Inhibition of human MDA-MB-231 breast cancer cell invasion by matrix
      metalloproteinase 3 involves degradation of plasminogen.
AB  - Matrix metalloproteinase (MMP)-3 inhibited human MDA-MB-231 breast cancer cell
      invasion through reconstituted basement membrane in vitro. Inhibition of invasion
      was dependent upon plasminogen and MMP-3 activation, was impaired by the peptide
      MMP-3 inhibitor Ac-Arg-Cys-Gly-Val-Pro-Asp-NH2 and was associated with: rapid MMP
      3-mediated plasminogen degradation to microplasminogen and angiostatin-like
      fragments; the removal of single-chain urokinase plasminogen activator from MDA
      MB-231 cell membranes; impaired membrane plasminogen association; reduced rate of
      tissue plasminogen activator (t-PA) and membrane-mediated plasminogen activation;
      and reduced laminin-degrading capacity. Purified human plasminogen lysine binding
      site-1 (kringles 1-3) exhibited a similar capacity to inhibit MDA-MB-231
      invasion, impair t-PA and cell membrane-mediated plasminogen activation and
      impair laminin degradation by plasmin. Our data provide evidence that MMP-3 can
      inhibit breast tumour cell invasion in vitro by a mechanism involving plasminogen
      degradation to fragments that limit plasminogen activation and the degradation of
      laminin. This supports the hypothesis that MMP-3, under certain conditions, may
      protect against tumour invasion, which would help to explain why MMP-3
      expression, associated with benign and early stage breast tumours, is frequently
      lost in advanced stage, aggressive, breast disease.

PMID- 12230558
TI  - Molecular cloning and functional expression of a gene encoding an antiarrhythmia
      peptide derived from the scorpion toxin.
AB  - From a cDNA library of Chinese scorpion Buthus martensii Karsch, full-length
      cDNAs of 351 nucleotides encoding precursors (named BmKIM) that contain signal
      peptides of 21 amino acid residues, a mature toxin of 61 residues with four
      disulfide bridges, and an extra Gly-Lys-Lys tail, were isolated. The genomic
      sequence of BmKIM was cloned and sequenced; it consisted of two exons disrupted
      by an intron of 1622 bp, the largest known in scorpion toxin genomes, inserted in
      the region encoding the signal peptide. The cDNA was expressed in Escherichia
      coli. The recombinant BmKIM was toxic to both mammal and insects. This is the
      first report that a toxin with such high sequence homology with an insect
      specific depressant toxin group exhibits toxicity to mammals. Using whole cell
      patch-clamp recording, it was discovered that the recombinant BmKIM inhibited the
      sodium current in rat dorsal root ganglion neurons and ventricular myocytes and
      protected against aconitine- induced cardiac arrhythmia.

PMID- 12230561
TI  - Directed evolution of a glutaryl acylase into an adipyl acylase.
AB  - Semi-synthetic cephalosporin antibiotics belong to the top 10 of most sold drugs,
      and are produced from 7-aminodesacetoxycephalosporanic acid (7-ADCA). Recently
      new routes have been developed which allow for the production of adipyl-7-ADCA by
      a novel fermentation process. To complete the biosynthesis of 7-ADCA a highly
      active adipyl acylase is needed for deacylation of the adipyl derivative. Such an
      adipyl acylase can be generated from known glutaryl acylases. The glutaryl
      acylase of Pseudomonas SY-77 was mutated in a first round by exploration
      mutagenesis. For selection the mutants were grown on an adipyl substrate. The
      residues that are important to the adipyl acylase activity were identified, and
      in a second round saturation mutagenesis of this selected stretch of residues
      yielded variants with a threefold increased catalytic efficiency. The effect of
      the mutations could be rationalized on hindsight by the 3D structure of the
      acylase. In conclusion, the substrate specificity of a dicarboxylic acid acylase
      was shifted towards adipyl-7-ADCA by a two-step directed evolution strategy.
      Although derivatives of the substrate were used for selection, mutants retained
      activity on the beta-lactam substrate. The strategy herein described may be
      generally applicable to all beta-lactam acylases.

PMID- 12230560
TI  - The crystal structure of coenzyme B12-dependent glycerol dehydratase in complex
      with cobalamin and propane-1,2-diol.
AB  - Recombinant glycerol dehydratase of Klebsiella pneumoniae was purified to
      homogeneity. The subunit composition of the enzyme was most probably alpha 2 beta
      2 gamma 2. When (R)- and (S)-propane-1,2-diols were used independently as
      substrates, the rate with the (R)-enantiomer was 2.5 times faster than that with
      the (S)-isomer. In contrast to diol dehydratase, an isofunctional enzyme, the
      affinity of the enzyme for the (S)-isomer was essentially the same or only
      slightly higher than that for the (R)-isomer (Km(R)/Km(S) = 1.5). The crystal
      structure of glycerol dehydratase in complex with cyanocobalamin and propane-1,2
      diol was determined at 2.1 A resolution. The enzyme exists as a dimer of the
      alpha beta gamma heterotrimer. Cobalamin is bound at the interface between the
      alpha and beta subunits in the so-called 'base-on' mode with 5,6
      dimethylbenzimidazole of the nucleotide moiety coordinating to the cobalt atom.
      The electron density of the cyano group was almost unobservable, suggesting that
      the cyanocobalamin was reduced to cob(II)alamin by X-ray irradiation. The active
      site is in a (beta/alpha)8 barrel that was formed by a central region of the
      alpha subunit. The substrate propane-1,2-diol and essential cofactor K+ are bound
      inside the (beta/alpha)8 barrel above the corrin ring of cobalamin. K+ is hepta
      coordinated by the two hydroxyls of the substrate and five oxygen atoms from the
      active-site residues. These structural features are quite similar to those of
      diol dehydratase. A closer contact between the alpha and beta subunits in
      glycerol dehydratase may be reminiscent of the higher affinity of the enzyme for
      adenosylcobalamin than that of diol dehydratase. Although racemic propane-1,2
      diol was used for crystallization, the substrate bound to glycerol dehydratase
      was assigned to the (R)-isomer. This is in clear contrast to diol dehydratase and
      accounts for the difference between the two enzymes in the susceptibility of
      suicide inactivation by glycerol.

PMID- 12230562
TI  - Redox-sensitive loops D and E regulate NADP(H) binding in domain III and domain I
      domain III interactions in proton-translocating Escherichia coli
      transhydrogenase.
AB  - Membrane-bound transhydrogenases are conformationally driven proton-pumps which
      couple an inward proton translocation to the reversible reduction of NADP+ by
      NADH (forward reaction). This reaction is stimulated by an electrochemical proton
      gradient, Delta p, presumably through an increased release of NADPH. The enzymes
      have three domains: domain II spans the membrane, while domain I and III are
      hydrophilic and contain the binding sites for NAD(H) and NADP(H), respectively.
      Separately expressed domain I and III together catalyze a very slow forward
      reaction due to tightly bound NADP(H) in domain III. With the aim of examining
      the mechanistic role(s) of loop D and E in domain III and intact cysteine-free
      Escherichia coli transhydrogenase by cysteine mutagenesis, the conserved residues
      beta A398, beta S404, beta I406, beta G408, beta M409 and beta V411 in loop D,
      and residue beta Y431 in loop E were selected. In addition, the previously made
      mutants betaD392C and betaT393C in loop D, and beta G430C and beta A432C in loop
      E, were included. All loop D and E mutants, especially beta I406C and beta G430C,
      showed increased ratios between the rates of the forward and reverse reactions,
      thus approaching that of the wild-type enzyme. Determination of values indicated
      that the former increase was due to a strongly increased dissociation of NADPH
      caused by an altered conformation of loops D and E. In contrast, the cysteine
      free G430C mutant of the intact enzyme showed the same inhibition of both forward
      and reverse rates. Most domain III mutants also showed a decreased affinity for
      domain I. The results support an important and regulatory role of loops D and E
      in the binding of NADP(H) as well as in the interaction between domain I and
      domain III.

PMID- 12230563
TI  - Chaperone and antichaperone activities of trigger factor.
AB  - Reduced denatured lysozyme tends to aggregate at neutral pH and competition
      between productive folding and aggregation substantially reduces the efficiency
      of refolding. Trigger factor, a folding catalyst and chaperone can, depending on
      the concentration of trigger factor and the solution conditions, cause either a
      substantial increase (chaperone activity) or a substantial decrease
      (antichaperone activity) in the recovery of native lysozyme as compared with
      spontaneous refolding. When trigger factor is working as a chaperone, the
      reactivation rates of lysozyme are decelerated and aggregation decreases with
      increasing trigger factor concentrations. Under conditions where antichaperone
      activity of trigger factor dominates, the reactivation rates of lysozyme are
      accelerated and aggregation is increased. Trigger factor and lysozyme were both
      released from the aggregates on re-solubilization with urea indicating that
      trigger factor participates directly in aggregate formation and is incorporated
      into the aggregates. The apparently dual effect of trigger factor toward
      refolding of lysozyme is a consequence of the peptide binding ability and may be
      important in regulation of protein biosynthesis.

PMID- 12230564
TI  - Characterization of the promoter for the mouse alpha 3 integrin gene.
AB  - The alpha 3 beta 1 integrin is an adhesion receptor for extracellular matrix
      proteins including isoforms of laminin, and the changes of its expression level
      in various cancer cells are thought to cause their malignant phenotypes. We have
      cloned an approximately 4 kb DNA fragment of the 5'-flanking region of the murine
      alpha 3 integrin gene and analyzed its promoter activity. Transfection of MKN1
      gastric carcinoma cells with serially truncated segments of the 5'-flanking
      region linked to a luciferase gene indicated that a 537-bp SalI/SacI fragment
      upstream of exon 1 was sufficient to promote high level gene expression. By 5'
      rapid amplification of cDNA ends (5'-RACE) using a cap site-labeled cDNA library,
      we determined one major and one minor transcription start sites in this region.
      The murine alpha 3 integrin gene was found to contain a CCAAT box, but to lack a
      TATA box. Luciferase assay following transfection with a series of deletion
      constructs of the SalI/SacI fragment revealed that the sequence between positions
      -260 and -119 bp (relative to the major transcription start site) is required for
      efficient transcription in gastric carcinoma cells. The sequence analysis of this
      segment showed the presence of several consensus sequences for transcription
      factors including Ets, GATA and MyoD/E-box binding factors. The introduction of
      mutation in one of the Ets-binding sequences greatly decreased its promoter
      activity, suggesting that the transcription of the alpha 3 integrin gene in these
      cells is regulated by the Ets-family of transcription factors.

PMID- 12230565
TI  - Solution NMR structure of five representative glycosylated polyene macrolide
      antibiotics with a sterol-dependent antifungal activity.
AB  - Glycosylated polyene macrolide antibiotics, as nystatins and amphotericins, are
      amphiphilic structures known to exert antifungal activity by disrupting the
      fungal cell membrane, leading to leakage of cellular materials, and cell death.
      This membrane disruption is strongly influenced by the presence and the exact
      nature of the membrane sterols. The solution structures of five representative
      glycosylated members, three tetraenes (pimaricin, nystatin A1 and rimocidin) and
      two heptaenes (candidin and vacidin A) have been calculated using geometric
      restraints derived from 1H-NMR data and random searches of their conformational
      space. Despite a different apparent structural order, the NMR solutions structure
      indicate that the hydroxyl groups all clustered on one side of the rod-shaped
      structures, and the glycosyl moieties are structurally conserved both in their
      conformation and their apparent order. The molecular structures afford an
      understanding of their selective interaction with the membrane sterols and the
      design of new polyene macrolides with improved activities.

PMID- 12230566
TI  - Characterization of phycoviolobilin phycoerythrocyanin-alpha 84-cystein-lyase
      (isomerizing) from Mastigocladus laminosus.
AB  - Cofactor requirements and enzyme kinetics have been studied of the novel, dual
      action enzyme, the isomerizing phycoviolobilin phycoerythrocyanin-alpha84-cystein
      lyase(PVB-PEC-lyase) from Mastigocladus laminosus, which catalyses both the
      covalent attachment of phycocyanobilin to PecA, the apo-alpha-subunit of
      phycoerythrocyanin, and its isomerization to phycoviolobilin. Thiols and the
      divalent metals, Mg2+ or Mn2+, were required, and the reaction was aided by the
      detergent, Triton X-100. Phosphate buffer inhibits precipitation of the proteins
      present in the reconstitution mixture, but at the same time binds the required
      metal. Kinetic constants were obtained for both substrates, the chromophore (Km =
      12-16 micro m, depending on [PecA], kcat approximately 1.2 x 10-4.s-1) and the
      apoprotein (Km = 2.4 micro m at 14 micro m PCB, kcat = 0.8 x 10-4.s-1). The
      kinetic analysis indicated that the reconstitution reaction proceeds by a
      sequential mechanism. By a combination of untagged and His-tagged subunits,
      evidence was obtained for a complex formation between PecE and PecF (subunits of
      PVB-PEC-lyase), and by experiments with single subunits for the prevalent
      function of PecE in binding and PecF in isomerizing the chromophore.

PMID- 12230567
TI  - Casein kinase 2 specifically binds to and phosphorylates the carboxy termini of
      ENaC subunits.
AB  - A number of findings have suggested the involvement of protein phosphorylation in
      the regulation of the epithelial Na+ channel (ENaC). A recent study has
      demonstrated that the C tails of the beta and gamma subunits of ENaC are subject
      to phosphorylation by at least three protein kinases [Shi, H., Asher, C.,
      Chigaev, A., Yung, Y., Reuveny, E., Seger, R. & Garty, H. (2002) J. Biol. Chem.
      277, 13539-13547]. One of them was identified as ERK which phosphorylates
      betaT613 and gammaT623 and affects the channel interaction with Nedd4. The
      current study identifies a second protein kinase as casein kinase 2 (CK2), or CK
      2-like kinase. It phosphorylates betaS631, a well-conserved serine on the beta
      subunit. Such phosphorylation is observed both in vitro using glutathione-S
      transferase-ENaC fusion proteins and in vivo in ENaC-expressing Xenopus oocytes.
      The gamma subunit is weakly phosphorylated by this protein kinase on another
      residue (gammaT599), and the C tail of alpha is not significantly phosphorylated
      by this kinase. Thus, CK2 may be involved in the regulation of the epithelial Na+
      channel.

PMID- 12230568
TI  - Inhibition of the NF-kappaB transcriptional activity by protein kinase A.
AB  - The cAMP-dependent protein kinase (PKA) signaling pathway plays a major role in a
      number of pathophysiological conditions. However, there have been conflicting
      evidences regarding the action of cAMP/PKA on nuclear factor- kappaB (NF-kappaB).
      In this study, we have explored the effect of cAMP/PKA on NF-kappaBeta activity
      and determined its molecular mechanism. PKA activating agents or expression of
      the catalytic subunit of PKA (PKAc) inhibited the NF-kappaBeta-dependent reporter
      gene expression induced by tumor necrosis factor alpha (TNFalpha). PKA activators
      affected neither IkappaBalpha phosphorylation, IkappaBetaalpha degradation, nor
      the NF-kappaBeta/DNA binding. Expression of PKAc inhibited the transactivation
      potential of Gal4-p65 (286-551) suggesting that the inhibitory action of PKA is
      through the C-terminal transactivation domain of p65 but not by phosphorylation
      of the consensus PKA recognition site containing serine at position 276.
      Overexpression of coactivators, CBP (CREB-binding protein) and p300, failed to
      reverse the PKA-mediated inhibition of p65 transactivation. Thus, the inhibitory
      action of the cAMP/PKA pathway on the transcriptional activity of NF-kappaB
      appears to be exhibited by modifying the C-terminal transactivation domain of
      p65, either directly or indirectly.

PMID- 12230569
TI  - Characterization and functional expression of cDNAs encoding thyrotropin
      releasing hormone receptor from Xenopus laevis.
AB  - Thyrotropin-releasing hormone receptor (TRHR) has already been cloned in mammals
      wherethyrotropin-releasing hormone (TRH) is known to act as a powerful stimulator
      of thyroid-stimulating hormone (TSH) secretion. The TRH receptor of amphibians
      has not yet been characterized, although TRH is specifically important in the
      adaptation of skin color to environmental changes via the secretion of alpha
      melanocyte-stimulating hormone (alpha-MSH). Using a dege-nerate PCR strategy, we
      report on the isolation of three distinct cDNA species encoding TRHR from the
      brain of Xenopus laevis. We have designated these as xTRHR1, xTRHR2 and xTRHR3.
      Analysis of the predicted amino acid sequences revealed that the three Xenopus
      TRHRs are only 54-62% identical and contain all the highly conserved residues
      constituting the TRH binding pocket. Amino acid sequences and phylogenetic
      analysis revealed that xTRHR1 is a member of TRHR subfamily 1 and xTRHR2 belongs
      to subfamily 2, while xTRHR3 is a new TRHR subtype awaiting discovery in other
      animal species. The three Xeno-pus TRHRs have distinct patterns of expression.
      xTRHR3 was abundant in the brain and much scarcer in the peripheral tissues,
      whereas xTRHR1 was found mainly in the stomach and xTRHR2 in the heart. The
      Xenopus TRHR subtype 1 was found specifically in the intestine, lung and urinary
      bladder. These observations suggest that the three xTRHRs each have specific
      functions that remain to be elucidated. Expression in Xenopus oocytes and HEK-293
      cells indicates that the three Xenopus TRHRs are fully functional and are coupled
      to the inositol phosphate/calcium pathway. Interestingly, activation of xTRHR3
      required larger concentrations of TRH compared with the other two receptors,
      suggesting marked differences in receptor binding, coupling or regulation.

PMID- 12230570
TI  - The molecular surface of proteolytic enzymes has an important role in stability
      of the enzymatic activity in extraordinary environments.
AB  - It is scientifically and industrially important to clarify the stabilizing
      mechanism of proteases in extraordinary environments. We used subtilisins ALP I
      and Sendai as models to study the mechanism. Subtilisin ALP I is extremely
      sensitive to highly alkaline conditions, even though the enzyme is produced by
      alkalophilic Bacillus, whereas subtilisin Sendai from alkalophilic Bacillus is
      stable under conditions of high alkalinity. We constructed mutant subtilisin ALP
      I enzymes by mutating the amino acid residues specific for subtilisin ALP I to
      the residues at the corresponding positions of amino acid sequence alignment of
      alkaline subtilisin Sendai. We observed that the two mutations in the C-terminal
      region were most effective for improving stability against surfactants and heat
      as well as high alkalinity. We predicted that the mutated residues are located on
      the surface of the enzyme structures and, on thebasis of three-dimensional
      modelling, that they are involved in stabilizing the conformation of the C
      terminal region. As proteolytic enzymes frequently become inactive due to
      autocatalysis, stability of these enzymes in an extraordinary environment would
      depend on the conformational stability of the molecular surface concealing
      scissile peptide bonds. It appeared that the stabilization of the molecular
      surface structure was effective to improve the stability of the proteolytic
      enzymes.

PMID- 12230571
TI  - Characterization of a chemosensory protein (ASP3c) from honeybee (Apis mellifera
      L.) as a brood pheromone carrier.
AB  - Chemosensory proteins (CSPs) are ubiquitous soluble small proteins isolated from
      sensory organs of a wide range of insect species, which are believed to be
      involved in chemical communication. We report the cloning of a honeybee CSP gene
      called ASP3c, as well as the structural and functional characterization of the
      encoded protein. The protein was heterologously secreted by the yeast Pichia
      pastoris using the native signal peptide. ASP3c disulfide bonds were assigned
      after trypsinolysis followed by chromatography and mass spectrometry combined
      with microsequencing. The pairing (Cys(I)-Cys(II), Cys(III)-Cys(IV)) was found to
      be identical to that of Schistocerca gregaria CSPs, suggesting that this pattern
      occurs commonly throughout the insect CSPs. CD measurements revealed that ASP3c
      mainly consists of alpha-helices, like other insect CSPs. Gel filtration analysis
      showed that ASP3c is monomeric at neutral pH. Using ASA, a fluorescent fatty acid
      anthroyloxy analogue as a probe, ASP3c was shown to bind specifically to large
      fatty acids and ester derivatives, which are brood pheromone components, in the
      micromolar range. It was unable to bind tested general odorants and other tested
      pheromones (sexual and nonsexual). This is the first report on a natural
      pheromonal ligand bound by a recombinant CSP with a measured affinity constant.

PMID- 12230572
TI  - Isolation of a putative peroxidase, a target for factors controlling foot
      formation in the coelenterate hydra.
AB  - In hydra, differentiated ectodermal cells of the foot region contain a peroxidase
      activity that can be used as a marker for foot-specific differentiation
      processes. Because the expression of the gene coding for the peroxidase must be
      tightly regulated during foot-specific differentiation, characterization of the
      protein and cloning of the corresponding gene should provide valuable tools for
      getting deeper insights into the regulation of foot-specific differentiation. In
      this paper we characterize the foot-specific peroxidase by biochemical,
      histochemical, and molecular biological methods. We show that it is localized in
      granules, and that it consists of a single component, the molecular mass of which
      is in the range of 43-45 kDa. Purification of the protein and subsequent cloning
      of its complementary DNA yielded two closely related clones, ppod1 and ppod2.
      Transcripts of ppod2 are abundant in the whole animal with the exception of the
      hypostome, the tentacles, and the foot; the expression of ppod1 matches exactly
      the localization of the foot-specific peroxidase.

PMID- 12230573
TI  - Supramolecular calsequestrin complex.
AB  - As recently demonstrated by overlay assays using calsequestrin-peroxidase
      conjugates, the major 63 kDa Ca(2+)-binding protein of the sarcoplasmic reticulum
      forms complexes with itself, and with junctin (26 kDa), triadin (94 kDa) and the
      ryanodine receptor (560 kDa) [Glover, L., Culligan, K., Cala, S., Mulvey, C. &
      Ohlendieck, K. (2001) Biochim. Biophys. Acta1515, 120-132]. Here, we show that
      variations in the relative abundance of these four central elements of excitation
      contraction coupling in different fiber types, and during chronic
      electrostimulation-induced fiber type transitions, are reflected by distinct
      alterations in the calsequestrin overlay binding patterns. Comparative
      immunoblotting with antibodies to markers of the junctional sarcoplasmic
      reticulum, in combination with the calsequestrin overlay binding patterns,
      confirmed a lower ryanodine receptor expression in slow soleus muscle compared to
      fast fibers, and revealed a drastic reduction of the RyR1 isoform in chronic low
      frequency stimulated tibialis anterior muscle. The fast-to-slow transition
      process included a distinct reduction in fast calsequestrin and triadin and a
      concomitant reduction in calsequestrin binding to these sarcoplasmic reticulum
      elements. The calsequestrin-binding protein junctin was not affected by the
      muscle transformation process. The increase in calsequestrin and decrease in
      junctin expression during postnatal development resulted in similar changes in
      the intensity of binding of the calsequestrin conjugate to these sarcoplasmic
      reticulum components. Aged skeletal muscle fibers tended towards reduced protein
      interactions within the calsequestrin complex. This agrees with the physiological
      concept that the key regulators of Ca(2+) homeostasis exist in a supramolecular
      membrane assembly and that protein-protein interactions are affected by isoform
      shifting underlying the finely tuned adaptation of muscle fibers to changed
      functional demands.

PMID- 12230574
TI  - NblA from Anabaena sp. PCC 7120 is a mostly alpha-helical protein undergoing
      reversible trimerization in solution.
AB  - The nblA family of genes encodes for small proteins necessary for the ordered
      degradation of phycobilisomes under certain stress conditions, a process known as
      chlorosis. Genes homologous to nblA seem to occur in all phycobilisome-containing
      organisms. However, to date, no molecular mechanism is known for the action of
      NblA, nor have the gene products been characterized to understand the physical
      properties of the molecule and thus help elucidate the mechanism on a structural
      basis. In this study we report on the first characterization of an NblA
      homologous gene product. The chromosomal gene from the cyanobacterium Anabaena
      sp. PCC 7120 was cloned, heterologously expressed in Escherichia coli and
      purified to apparent homogeneity. This allowed the protein to be characterized by
      analytical ultracentrifugation and CD spectroscopy. These experiments show that
      the NblA protein has a mostly alpha-helical structure, undergoing an association
      reaction of folded monomers to form trimers in solution. No dimers are
      detectable.

PMID- 12230575
TI  - Role of Ca2+/calmodulin regulated signaling pathways in chemoattractant induced
      neutrophil effector functions. Comparison with the role of phosphotidylinositol-3
      kinase.
AB  - In human neutrophils, both changes in intracellular Ca(2+) concentrations,
      [Ca(2+)]i, and activation of phosphatidylinositol-3 kinase (PtdIns3K) have been
      proposed to play a role in regulating cellular function induced by
      chemoattractants. In this study we have investigated the role of [Ca(2+)]i and
      its effector molecule calmodulin in human neutrophils. Increased [Ca(2+)]i alone
      was sufficient to induce phosphorylation of extracellular signal-regulated
      protein kinase 2 (ERK2), p38 mitogen activated kinase (p38 MAPK), protein kinase
      B (PKB) and glycogen synthase kinase-3alpha (GSK-3alpha). Inhibition of
      calmodulin using a calmodulin antagonist N-(6-aminohexyl)-5-chloro-1
      naphthalenesulfonamide (W7), did not effect N-formyl-methionyl-leucyl
      phenylalanine (fMLP) induced ERK, p38 MAPK or GSK-3alpha phosphorylation, but
      attenuated fMLP induced PKB phosphorylation. PCR analysis of human neutrophil
      cDNA demonstrated variable expression of members of the Ca(2+)/calmodulin
      dependent kinase family. The roles of calmodulin and PtdIns3K in regulating
      neutrophil effector functions were further compared. Neutrophil migration was
      abrogated by inhibition of calmodulin, while no effect was observed when PtdIns3K
      was inhibited. In contrast, production of reactive oxygen species was sensitive
      to inhibition of both calmodulin and PtdIns3K. Finally, we demonstrated that
      chemoattractants are unable to modulate neutrophil survival, despite activation
      of PtdIns3K and elevation [Ca(2+)]i. Taken together, our data indicate critical
      roles for changes in [Ca(2+)]i and calmodulin activity in regulating neutrophil
      migration and respiratory burst and suggest that chemoattractant induced PKB
      phosphorylation may be mediated by a Ca(2+)/calmodulin sensitive pathway in human
      neutrophils.

PMID- 12230576
TI  - The oxidative effect of bacterial lipopolysaccharide on native and cross-linked
      human hemoglobin as a function of the structure of the lipopolysaccharide.
AB  - The binding of lipopolysaccharide (LPS, also known as bacterial endotoxin) to
      human hemoglobin is known to result in oxidation of hemoglobin to methemoglobin
      and hemichrome. We have investigated the effects of the LPSs from smooth and
      rough Escherichia coli and Salmonella minnesota on the rate of oxidation of
      native oxyhemoglobin A0 and hemoglobin cross-linked between the alpha-99 lysines.
      For cross-linked hemoglobin, both smooth LPSs produced a rate of oxidation faster
      than the corresponding rough LPSs, indicating the importance of the binding of
      LPS to the hemoglobin. The effect of the LPS appeared to be largely on the
      initial fast phase of the oxidation reaction, suggesting modification of the heme
      pocket of the alpha chains. For hemoglobin A0, the rates of oxidation produced by
      rough and smooth LPSs were very similar, suggesting the possibility that the
      effect of the LPSs was to cause dissociation of hemoglobin into dimers. The
      participation of cupric ion in the oxidation process was demonstrated in most
      cases. In contrast, the rate of oxidation of cross-linked hemoglobin by the LPSs
      of both the rough and smooth E. coli was not affected by the presence of
      chelators, suggesting that cupric ion had previously bound to these LPSs.
      Overall, these data suggest that the physiological effectiveness of hemoglobin
      solutions now being developed for clinical use may be decreased by the presence
      of lipopolysaccharide in the circulation of recipients.

PMID- 12230577
TI  - A chromatin-associated protein from pea seeds preferentially binds histones H3
      and H4.
AB  - Pisum sativum p16 is a protein present in the chromatin of ungerminated embryonic
      axes. The purification of p16 and the isolation of a cDNA clone of psp54, the
      gene encoding its precursor have been recently reported [Castillo, J., Rodrigo,
      M. I., Marquez, J. A., Zuniga, A and Franco, L. (2000) Eur. J. Biochem.267, 2156
      2165]. In the present paper, we present data showing that p16 is a nuclear
      protein. First, after subcellular fractionation, p16 was clearly found in nuclei,
      although the protein is also present in other organelles. Immunocytochemical
      methods also confirm the above results. p16 seems to be firmly anchored to
      chromatin, as only extensive DNase I digestion of nuclei allows its release. Far
      Western and pull-down experiments demonstrate a strong in vitro interaction
      between p16 and histones, especially H3 and H4, suggesting that p16 is tethered
      to chromatin through histones. Because the psp54 gene is specifically expressed
      during the late development of seed, the role of p16 might be related to the
      changes that occur in chromatin during the processes of seed maturation and
      germination.

PMID- 12230578
TI  - Hexadecylphosphocholine inhibits phosphatidylcholine biosynthesis and the
      proliferation of HepG2 cells.
AB  - Hexadecylphosphocholine (HePC) is a synthetic lipid representative of a new group
      of antiproliferative agents, alkylphosphocholines (APC), which are promising
      candidates in anticancer therapy. Thus we have studied the action of HePC on the
      human hepatoblastoma cell line HepG2, which is frequently used as a model for
      studies into hepatic lipid metabolism. Non-toxic, micromolar concentrations of
      HePC exerted an antiproliferative effect on this hepatoma cell line. The
      incorporation into phosphatidylcholine (PC) of the exogenous precursor [methyl
      14C]choline was substantially reduced by HePC. This effect was not due to any
      alteration in choline uptake by the cells, the degradation rate of PC or the
      release of PC into the culture medium. As anaccumulation of soluble choline
      derivatives points to CTP:phosphocholine cytidylyltransferase (CT) as the target
      of HePC activity we examined its effects on the different enzymes involved in the
      biosynthesis of PC via CDP-choline. Treatment with HePC altered neither the
      activity of choline kinase (CK) nor that of diacylglycerol
      cholinephosphotransferase (CPT), but it did inhibit CT activity in HepG2 cells.
      In vitro HePC also inhibited the activity of cytosolic but not membrane-bound CT.
      Taken together our results suggest that HePC interferes specifically with the
      biosynthesis of PC in HepG2 cells by depressing CT translocation to the membrane,
      which may well impair their proliferation.

PMID- 12230579
TI  - Kinetics of violaxanthin de-epoxidation by violaxanthin de-epoxidase, a
      xanthophyll cycle enzyme, is regulated by membrane fluidity in model lipid
      bilayers.
AB  - This paper describes violaxanthin de-epoxidation in model lipid bilayers.
      Unilamellar egg yolk phosphatidylcholine (PtdCho) vesicles supplemented with
      monogalactosyldiacylglycerol were found to be a suitable system for studying this
      reaction. Such a system resembles more the native thylakoid membrane and offers
      better possibilities for studying kinetics and factors controlling de-epoxidation
      of violaxanthin than a system composed only ofmonogalactosyldiacylglycerol and is
      commonly used in xanthophyll cycle studies. The activity of violaxanthin de
      epoxidase (VDE) strongly depended on the ratio of monogalactosyldiacylglycerol to
      PtdCho in liposomes. The mathematical model of violaxanthin de-epoxidation was
      applied to calculate the probability of violaxanthin to zeaxanthin conversion at
      different phases of de-epoxidation reactions. Measurements of deepoxidation rate
      and EPR-spin label study at different temperatures revealed that dynamic
      properties of the membrane are important factors that might control conversion of
      violaxanthin to antheraxanthin. A model of the molecular mechanism of
      violaxanthin de-epoxidation where the reversed hexagonal structures (mainly
      created by monogalactosyldiacylglycerol) are assumed to be required for
      violaxanthin conversion to zeaxanthin is proposed. The presence of
      monogalactosyldiacylglycerol reversed hexagonal phase was detected in the
      PtdCho/monogalactosyldiacylglycerol liposomes membrane by 31P-NMR studies. The
      availability of violaxanthin for de-epoxidation is a diffusion-dependent process
      controlled by membrane fluidity. The significance of the presented results for
      understanding themechanism of violaxanthin de-epoxidation in native thylakoid
      membranes is discussed.

PMID- 12230580
TI  - Sub-zero temperature inactivation of carboxypeptidase Y under high hydrostatic
      pressure.
AB  - High hydrostatic pressure induced cold inactivation of carboxypeptidase Y.
      Carboxypeptidase Y was fully active when exposed to subzero temperature at 0.1
      MPa; however, the enzyme became inactive when high hydrostatic pressure and
      subzero temperature were both applied. When the enzyme was treated at pressures
      higher than 300 MPa and temperatures lower than -5 degrees C, it underwent an
      irreversible inactivation in which nearly 50% of the alpha-helical structure was
      lost as judged by circular dichroism spectral analysis. When the applied pressure
      was limited to below 200 MPa, the cold inactivation process appeared to be
      reversible. In the presence of reducing agent, this reversible phenomenon,
      observed at below 200 MPa, diminished to give an inactive enzyme; the agent
      reduces some of disulfide bridge(s) in an area of the structure that is newly
      exposed area because of the cold inactivation. Such an area is unavailable if
      carboxypeptidase Y is in its native conformation. Because all the disulfide
      bridges in carboxypeptidase Y locate near the active site cleft, it is suggested
      that the structural destruction, if any, occurs preferentially in this disulfide
      rich area. A possible mechanism of pressure-dependent cold inactivation of CPY is
      to destroy the alpha-helix rich region, which creates an hydrophobic environment.
      This destruction is probably a result of the reallocation of water molecules.
      Experiments carried out in the presence of denaturing agents (SDS, urea, GdnHCl),
      salts, glycerol, and sucrose led to a conclusion consistent with the idea of
      water reallocation.

PMID- 12230581
TI  - The three typical aspartic proteinase genes of Arabidopsis thaliana are
      differentially expressed.
AB  - Genomic sequencing has identified three different typical plant aspartic
      proteinases in the genome of Arabidopsis thaliana, named Pasp-A1, A2 and A3. A1
      is identical to a cDNA we had previously isolated and the two others produce
      proteins 81 and 63% identical to that predicted protein. Sequencing of the
      aspartic proteinase protein purified from Arabidopsis seeds showed that the
      peptides are derived from two of these genes, A1 and A2. Using gene specific
      probes, we have analyzed RNA from different tissues and found these three genes
      are differentially expressed. A1 mRNA is detected in all tissues analyzed and
      more abundant in leaves during the light phase of growth. The other two genes are
      expressed either primarily in flowers (A3) or in seeds (A2). Insitu hybridization
      demonstrated that all three genes are expressed in many cells of the seeds and
      developing seed pods. The A1 and A3 genes are expressed in the sepals and petals
      of flowers as well as the outer layer of the style, but are not expressed in the
      transmitting tract or on the stigmatal surface. The A2 gene is weakly expressed
      only in the transmitting tissue of the style. All three genes are also expressed
      in the guard cells of sepals. These data suggest multiple roles for aspartic
      proteinases besides those proposed in seeds.

PMID- 12230582
TI  - Cellular retinol-binding protein type II (CRBPII) in adult zebrafish (Danio
      rerio). cDNA sequence, tissue-specific expression and gene linkage analysis.
AB  - We have determined the nucleotide sequence of a zebrafish cDNA clone that codes
      for a cellular retinol-binding protein type II (CRBPII). Radiation hybrid mapping
      revealed that the zebrafish and human CRBPII genes are located in syntenic
      groups. In situ hybridization and emulsion autoradiography localized the CRBPII
      mRNA to the intestine and the liver of adult zebrafish. CRBPII and intestinal
      fatty acid binding protein (I-FABP) mRNA was colocalized to the same regions
      along the anterior-posterior gradient of the zebrafish intestine. Similarly,
      CRBPII and I-FABP mRNA are colocalized in mammalian and chicken intestine. CRBPII
      mRNA, but not I-FABP mRNA, was detected in adult zebrafish liver which is in
      contrast to mammals where liver CRBPII mRNA levels are high during development
      but rapidly decrease to very low or undetectable levels following birth. CRBPII
      and I-FABP gene expression appears therefore to be co-ordinately regulated in the
      zebrafish intestine as has been suggested for mammals and chicken, but CRBPII
      gene expression is markedly different in the liver of adult zebrafish compared to
      the livers of mammals. As such, retinol metabolism in zebrafish may differ from
      that of mammals and require continued production of CRBPII in adult liver. The
      primary sequence of the coding regions of fish and mammalian CRBPII genes, their
      relative chromosomal location in syntenic groups and possibly portions of the
      control regions involved in regulation of CRBPII gene expression in the intestine
      appear therefore to have been conserved for more than 400 million years.

PMID- 12230583
TI  - Novel bradykinins and their precursor cDNAs from European yellow-bellied toad
      (Bombina variegata) skin.
AB  - Two novel bradykinin-related peptides (Ala3,Thr6)-bradykinin and (Val1,Thr3,Thr6)
      bradykinin, were identified by a systematic sequencing study of peptides in the
      defensive skin secretion of the yellow-bellied toad, Bombina variegata. These
      peptides are the first amphibian skin bradykinins to exhibit amino acid
      substitutions at the Pro3 position of the bradykinin nonapeptide. Previously
      reported bradykinins from other Bombina species were not detected. Respective
      precursor cDNAs, designated BVK-1 and BVK-2, respectively, were cloned from a
      skin library by 3'- and 5'-RACE reactions. BVK-1 contained an open-reading frame
      of 97 amino acids encoding a single copy of (Ala3,Thr6)-bradykinin and similarly,
      the open-reading frame of BVK-2 consisted of 96 amino acids encoding a single
      copy of (Val1,Thr3,Thr6)-bradykinin. Synthetic replicates of each novel
      bradykinin were found to be active on mammalian arterial and small intestinal
      smooth muscle preparations. The structural diversity of bradykinins in amphibian
      defensive skin secretions may be related to defence against specific predators.

PMID- 12230589
TI  - Cancer and Development with Emphasis on Neurobiology and Cellular
      Microenvironment. Abstracts of the 12th International Conference of the
      International Society of Differentiation. 14-17 September 2002, Lyon, France.

PMID- 12230584
TI  - Molecular modeling of the dimeric structure of human lipoprotein lipase and
      functional studies of the carboxyl-terminal domain.
AB  - Lipoprotein lipase (LPL) plays a key role in lipid metabolism. Molecular modeling
      of dimeric LPL was carried out using insight ii based upon the crystal structures
      of human, porcine, and horse pancreatic lipase. The dimeric model reveals a
      saddle-shaped structure and the key heparin-binding residues in the amino
      terminal domain located on the top of this saddle. The models of two dimeric
      conformations - a closed, inactive form and an open, active form - differ with
      respect to how surface-loop positions affect substrate access to the catalytic
      site. In the closed form, the surface loop covers the catalytic site, which
      becomes inaccessible to solvent. Large conformational changes in the open form,
      especially in the loop and carboxyl-terminal domain, allow substrate access to
      the active site. To dissect the structure-function relationships of the LPL
      carboxyl-terminal domain, several residues predicted by the model structure to be
      essential for the functions of heparin binding and substrate recognition were
      mutagenized. Arg405 plays an important role in heparin binding in the active
      dimer. Lys413/Lys414 or Lys414 regulates heparin affinity in both monomeric and
      dimeric forms. To evaluate the prediction that LPL forms a homodimer in a 'head
      to-tail' orientation, two inactive LPL mutants - a catalytic site mutant (S132T)
      and a substrate-recognition mutant (W390A/W393A/W394A) - were cotransfected into
      COS7 cells. Lipase activity could be recovered only when heterodimerization
      occurred in a head-to-tail orientation. After cotransfection, 50% of the wild
      type lipase activity was recovered, indicating that lipase activity is determined
      by the interaction between the catalytic site on one subunit and the substrate
      recognition site on the other.

PMID- 12230590
TI  - Back to vitamins?

PMID- 12230591
TI  - Migraine: preventive treatment.
AB  - Migraine is a common episodic headache disorder. A comprehensive headache
      treatment plan includes acute attack treatment to relieve pain and impairment and
      long-term preventive therapy to reduce attack frequency, severity, and duration.
      Circumstances that might warrant preventive treatment include: (i) migraine that
      significantly interferes with the patient's daily routine despite acute
      treatment; (ii) failure, contraindication to, or troublesome side-effects from
      acute medications; (iii) overuse of acute medications; (iv) special
      circumstances, such as hemiplegic migraine; (v) very frequent headaches (more
      than two a week); or (vi) patient preference. Start the drug at a low dose. Give
      each treatment an adequate trial. Avoid interfering, overused, and
      contraindicated drugs. Re-evaluate therapy. Be sure that a woman of childbearing
      potential is aware of any potential risks. Involve patients in their care to
      maximize compliance. Consider co-morbidity. Choose a drug based on its proven
      efficacy, the patient's preferences and headache profile, the drug's side
      effects, and the presence or absence of coexisting or co-morbid disease. Drugs
      that have documented high efficacy and mild to moderate adverse events (AEs)
      include beta-blockers, amitriptyline, and divalproex. Drugs that have lower
      documented efficacy and mild to moderate AEs include selective serotonin reuptake
      inhibitors (SSRIs), calcium channel antagonists, gabapentin, topiramate,
      riboflavin, and non-steroidal anti-inflammatory drugs.

PMID- 12230592
TI  - Hydroxocobalamin, a nitric oxide scavenger, in the prophylaxis of migraine: an
      open, pilot study.
AB  - Drugs which directly counteract nitric oxide (NO), such as endothelial receptor
      blockers, NO-synthase inhibitors, and NO-scavengers, may be effective in the
      acute treatment of migraine, but are also likely to be effective in migraine
      prophylaxis. In the underlying pilot study the prophylactic effect of the NO
      scavenger hydroxocobalamin after intranasal administration in migraine was
      evaluated. Twenty patients, with a history of migraine of > 1 year and with two
      to eight migraine attacks per month, were included in an open trial. A baseline
      period was followed by an active treatment period of 3 months with 1 mg
      intranasal hydroxocobalamin daily. Patients were instructed to complete a diary
      in which details of each attack were described. A reduction in migraine attack
      frequency of >/ or = 50% was seen in 10 of 19 patients, which corresponds to 53%
      of the patients (responders). A reduction of > or = 30% was noted in 63% of the
      patients. The mean attack frequency in the total study population showed a
      reduction from 4.7 +/- 1.7 attacks per month to 2.7 +/- 1.6 (P < 0.001). For the
      responders the migraine attack frequency was reduced from 5.2 +/- 1.9 (baseline)
      to 1.9 +/- 1.3 attacks per month (P < 0.005), while for those who did not respond
      a non-significant reduction was found: 4.1 +/- 1.4 to 3.7 +/- 1.5 (P > 0.1). A
      reduction was also observed for the total duration of the migraine attacks per
      month, the total number of migraine days per month and the number of medication
      doses for acute treatment used per month. This is the first prospective, open
      study indicating that intranasal hydroxocobalamin may have a prophylactic effect
      in migraine. As a percentage of responders in prophylactic trials of > 35-40% is
      unlikely to be a placebo effect, a double-blind study is warranted.

PMID- 12230593
TI  - Greater occipital nerve blockade for cluster headache.
AB  - Cluster headache is perhaps the most painful of the primary headache disorders.
      Its treatment includes acute, transitional, and preventive therapy. Despite the
      availability of many treatments, cluster headache patients can still be difficult
      to treat. We treated 14 cluster headache patients with greater occipital nerve
      block as transitional therapy (treatment initiated at the same time as preventive
      therapy). The mean number of headache-free days was 13.1 + 23.6. Four patients
      (28.5%) had a good response, five (35.7%) a moderate, and five (35.7%) no
      response. The greater occipital nerve block was well tolerated with no adverse
      events. Headache intensity, frequency and duration were significantly decreased
      comparing the week before with the week after the nerve block (P < 0.003, P =
      0.003, P < 0.005, respectively). Greater occipital nerve blockade is a
      therapeutic option for the transitional treatment of cluster headache.

PMID- 12230594
TI  - The efficacy and safety of Tanacetum parthenium (feverfew) in migraine
      prophylaxis--a double-blind, multicentre, randomized placebo-controlled dose
      response study.
AB  - Tanacetum parthenium (feverfew), is a well-known herb for the prophylactic
      treatment of migraine. The primary objective was to show a dose-response of a new
      stable extract (MIG-99) reproducibly manufactured with supercritical CO2 from
      feverfew (T. parthenium). Furthermore, the study should provide data on the
      safety and tolerability of MIG-99. In a randomized, double-blind, multicentre,
      controlled trial with an adaptive design, the clinical efficacy and safety of
      three dosages of MIG-99 (2.08 mg; 6.25 mg; 18.75 mg t.i.d.) were compared with
      placebo. The patients (n = 147) suffered from migraine with and without aura
      according to International Headache Society (IHS) criteria and were treated with
      one of the study medications for 12 weeks after a 4-week baseline period. The
      primary efficacy parameter was the number of migraine attacks during the last 28
      days of the treatment period compared with baseline. Secondary endpoints were
      total and average duration and intensity of migraine attacks, mean duration of
      the single attack, number of days with accompanying migraine symptoms, number of
      days with inability to work due to migraine as well as type and amount of
      additionally taken medications for the treatment of migraine attacks. The design
      of the study included a pre-planned adaptive interim analysis for patients with
      at least four migraine attacks within the baseline period. With respect to the
      primary and secondary efficacy parameter, a statistically significant difference
      was not found between the overall and the confirmatory intention-to-treat (ITT)
      sample in the exploratorily analysed four treatment groups. The frequency of
      migraine attacks for the predefined confirmatory subgroup of patients (n = 49)
      with at least four migraine attacks during the baseline period decreased in a
      dose-dependent manner (P = 0.001). The highest absolute change of migraine
      attacks was observed under treatment with 6.25 mg t.i.d. (mean +/- SD = -1.8 +/-
      1.5 per 28 days) compared with placebo (-0.3 +/- 1.9; P = 0.02). Overall, 52 of
      147 (35%) patients reported at least one adverse event (AE). The incidence of AEs
      in the active treatment groups was similar to that in the placebo group, and no
      dose-related effect was observed in any safety parameter. MIG-99 failed to show a
      significant migraine prophylactic effect in general. Accordingly, in the ITT
      analysis a dose-response relationship could not be observed. MIG-99 was shown to
      be effective only in a small predefined subgroup of patients with at least four
      attacks during the 28-day baseline period where the most favourable benefit-risk
      ratio was observed with a dosage of three capsules of 6.25 mg MIG-99 extract per
      day. Because of the low number of patients, these findings need to be verified in
      a larger sample. The incidence of AEs was similar for all treatment groups.

PMID- 12230595
TI  - 3D kinematic analysis and clinical evaluation of neck movements in patients with
      whiplash injury.
AB  - In recent decades whiplash injuries, being a major reason for compensation
      claims, have become increasingly important in forensic medicine. In view of this,
      a reliable diagnostic method of assessing cervical range of motion (ROM) is
      needed. The aim of the present study was to evaluate neck function with a 3D
      kinematic method compared with clinical evaluation in whiplash injury. Seventy
      consecutive patients (M/F = 18/52) with a history of whiplash injury (WH) and 46
      healthy volunteers (M/F = 24/22), mean age, respectively 33 +/- 9 and 28 +/- 6
      years (mean+/-SD) entered the study. Patients suffered from neck pain and/or
      unilateral headache. A computerized kinematic analysis of the ROM (Elite system)
      using passive markers and two infrared TV cameras was used. Clinical evaluation
      of active ROM was also performed both in patients and in 61 controls (M/F =
      23/38; mean age 47 +/- 18 years). Thirty out of 70 patients were tested at the
      time of their first consultation (T0) and 6 months later (T6), and 12 were also
      followed up after a year (T12). All neck movements, except extension, were
      significantly reduced in WH subjects compared with controls, in particular
      lateral bending. Comparing ROM at T0, T6 and T12, no significant differences were
      found. A global index of motion (GIM), obtained by calculating the sum of ROM in
      absolute value for all the movements acquired, was significantly reduced in WH
      compared with control subjects. The interobserver reliability of the clinical
      evaluation was globally acceptable. On the basis of the clinical evaluation, a
      significantly reduced ROM was found in all movements in WH subjects compared with
      an age-matched population. Computing the number of impaired cervical movements
      (ICMs), a significantly higher number was observed in WH patients than in
      controls, showing a decreasing trend at T6 and T12, with a significant
      improvement at T6 vs. T0. The computerized study of neck ROM may constitute a
      useful tool in the evaluation of WH at baseline and follow-up.

PMID- 12230597
TI  - Familial cyclic vomiting syndrome.
AB  - A family is described in which four members suffer from cycling vomiting syndrome
      (CVS), without additional symptoms. So far, only a few CVS families have been
      described in literature, and most patients belonging to these families had other
      symptoms in addition to CVS. We conclude that 'pure' CVS may also be a hereditary
      disorder. Its relation to migraine will be discussed.

PMID- 12230596
TI  - Migraine, major depression, panic disorder, and personality traits in women aged
      40-74 years: a population-based study.
AB  - This study investigates the associations between migraine on the one hand and
      lifetime major depression, lifetime panic disorder, and neuroticism evaluated
      using the Swedish universities Scales of Personality on the other. A neurologist
      clinically assessed 728 women aged 40-74 years attending a population-based
      mammography screening programme. The associations between lifetime migraine and
      personality traits and psychiatric disorders were insignificant in multivariable
      analysis. However, in old women (60-74 years) the risk for active migraine was
      strongly associated with a history of major depression and high levels of stress
      susceptibility and somatic trait anxiety. Furthermore, in old women, high levels
      of stress susceptibility and somatic trait anxiety were associated with low
      ratings of migraine pain intensity and lower levels of these traits with high
      ratings after controlling for disability during migraines, whereas there were
      only small differences in middle-aged women. The results suggest that certain
      aspects of neuroticism are important mental correlates of the ability of old
      women to endure migraine pain.

PMID- 12230598
TI  - Reflux-triggered migraine headache originating from the upper gum/teeth.
AB  - Two patients with migraine are described who also suffered from gastric reflux.
      The reflux triggered headaches that originated from the upper gum/teeth and
      responded to specific reflux treatment.

PMID- 12230599
TI  - Spontaneous carotid artery dissection with cluster-like headache.
AB  - A case of carotid artery dissection in a 41-year-old-woman is described whose
      main symptom was cluster-like pain. The case is interesting for its atypical
      presentation with only two other like cases in the literature, and the site of
      dissection, localized in the intrapetrous curvature of the carotid artery. The
      case highlights the need for active co-operation between clinician and
      neuroradiologist during neuroimaging assessment which must be focused on the
      clinical evaluation of the individual patient so as to avoid error, particularly
      in atypical cases.

PMID- 12230600
TI  - The chronic whiplash syndrome--a case of attributional pathosis?

PMID- 12230602
TI  - The hemicrania continua diagnosis.

PMID- 12230604
TI  - Abstracts of the 14th Migraine Trust International Symposium. London, United
      Kingdom. September 23-26, 2002.

PMID- 12230607
TI  - Levels of urinary inter-alpha-trypsin inhibitor trimer as a function of age and
      sex-hormone status in males and females not forming stones.
AB  - OBJECTIVES: To determine if levels of inter-alpha-trypsin inhibitor (I alpha TI)
      trimer differ in normal individuals based on age, gender or hormonal status, as
      the regulation of calcium oxalate (CaOx) crystallization inhibitors, e.g. by sex
      steroids, could be a mechanism contributing to the differences in CaOx
      urolithiasis between the sexes. SUBJECTS AND METHODS: Voided urine samples were
      collected from normal males and females. In Experiment 1 samples were grouped by
      gender and age, i.e. paediatric (PED) < or = 10 years, male (M) 21, female (F)
      14; young adult (YGAD) 20-30 years, M 23, F 18; adults (AD), 35-50 year, M 25, F
      13; adults aged > or = 60 years (> 60), M 24, F 16 (totals, M 93, F 61). In
      Experiment 2 samples were grouped by gender, age and hormonal status, i.e. PED, M
      24, F 17; AD, M 24, F 22; > 60 and not on hormonal therapy, M 23, F 30; M > 60
      and on androgen deprivation therapy (ANDEP) 18; and F > 60 on oestrogen
      supplementation, F+EST, 18 (total M 89, F 85). Levels of urinary I alpha TI
      trimer were determined by immunoblotting and enhanced chemiluminescence, and
      relative densities of the bands determined. RESULTS: In both experiments the
      relative levels of I alpha TI-trimer were 2-7 times higher in M-PED than in all
      other groups of males (P < or = 0.007). Among adult males, I alpha TI-trimer
      levels were similar in all groups, including ANDEP (P > or = 0.9). There were no
      differences in the relative levels of I alpha TI-trimer among any of the groups
      of females, regardless of age or hormonal status (P > or = 0.7). CONCLUSIONS: In
      males a decrease in I alpha TI-trimer was associated with the onset of adulthood
      and entry into the 'stone-forming years'. Females did not show this decrease, and
      neither sex showed an increase in I alpha TI-trimer in the > 60 group, when the
      incidence of CaOx urolithiasis is supposedly declining. While changes in urinary
      I alpha TI-trimer levels in males may reflect maturational changes in the kidney,
      overall these data do not support the hypothesis that the age-related changes in
      the incidence of urolithiasis are paralleled by changes in the expression I alpha
      TI-trimer. Additionally, the sex steroids do not appear to acutely regulate the
      expression of I alpha TI-trimer in adults, making differences in I alpha TI
      trimer levels unlikely to be the reason for the disparity in the incidence of
      CaOx urolithiasis between the sexes.

PMID- 12230608
TI  - Intra-ureteric capsaicin in loin pain haematuria syndrome: efficacy and
      complications.
AB  - OBJECTIVE: To evaluate the safety and efficacy of intra-ureteric capsaicin for
      loin pain haematuria syndrome (LPHS). PATIENTS AND METHODS: In an open
      prospective pilot study, four middle-aged patients (three women and one man) with
      LPHS resistant to therapies such as splanchnic nerve block, psychological
      treatment or renal autotransplantation (one) were assessed. An intra-ureteric
      infusion of capsaicin (30 mg/100 mL of 30% alcohol in saline) for 30 min with
      bladder irrigation was administered under general anaesthesia, with a subsequent
      intravenous patient-controlled narcotic analgesic pump for pain control. Double
      concentration capsaicin was used for second infusions, if necessary when the
      response to the earlier infusion was inadequate or incomplete. RESULTS: The first
      patient had experienced reduced pain levels for the first 3 months only, with no
      benefit from the subsequent treatments with higher doses of capsaicin (60 mg).
      The second patient with recurrent pain in an autotransplanted kidney had no
      benefit from either a 30 or 60 mg capsaicin infusion a month apart, but developed
      a fibrotic stricture at the transplant pelvi-ureteric junction, requiring
      pyelocystoplasty. The third patient with concurrent depression had no benefit
      from a 30-mg infusion of capsaicin. The fourth patient experienced no pain relief
      from a 30 mg infusion of capsaicin but developed proteinuria secondary to
      mesangial proliferative glomerulonephritis, ureteric inflammation needing
      stenting within 7 days of treatment and subsequently nephrectomy for a
      nonfunctioning kidney at 3 months. CONCLUSION: Intra-ureteric capsaicin was
      neither effective nor safe in LPHS; the contribution of the alcohol diluent
      cannot be excluded.

PMID- 12230609
TI  - The differences in health outcomes between Web-based and paper-based
      implementation of a clinical pathway for radical nephrectomy.
AB  - OBJECTIVE: To evaluate the effects of a web-based clinical pathway (WCP) for
      radical nephrectomy on patient care, and to compare the effects with those of a
      paper-based clinical pathway (PCP). PATIENTS AND METHODS: Patients with renal
      cell carcinoma and who underwent radical nephrectomy were enrolled into the
      study. The results of using the WCP for radical nephrectomy from July 2000 to
      August 2001 were compared with those using the PCP between May 1999 and June
      2000. The mean hospital stay, average admission charges, six quality indicators,
      and the advantages of the WCP were determined. RESULTS: Using a WCP for radical
      nephrectomy reduced the hospital stay and admission charges by as much as the
      PCP. A similar number of patients had variances from the WCP as with the PCP (P =
      0.407), but the number of undetected variances and the variance detection time in
      the WCP were significantly less (P = 0.0193 and 0.0162). Implementing a WCP also
      improved the quality of care by as much as a PCP. CONCLUSIONS: Using a WCP for
      radical nephrectomy can improve health outcomes by reducing the hospital stay and
      admission charges, and by improving the quality of care by as much as a PCP.
      Furthermore, the WCP was more accurate and faster than the PCP in detecting
      variances.

PMID- 12230610
TI  - Prognostic implications of histological features in patients with chromophobe
      cell renal carcinoma.
AB  - OBJECTIVE: To assess the relationship between the histological features of renal
      chromophobe cell carcinoma (CCC) and clinical outcome in patients with renal cell
      carcinoma. PATIENTS AND METHODS: From 1957 to 1996, 41 patients with CCC of the
      kidney (4.9% of all kidney carcinomas) were treated at our university hospitals.
      Of these histologically defined cases, four who died from other types of cancer
      and two who were lost to follow-up were excluded, leaving 35 patients in the
      study; the carcinoma was classified as the typical variant in 26 and the
      eosinophilic variant in nine. Based on the differences of the variants, the
      histological features affecting prognosis were analysed. RESULTS: The overall
      survival rates at 1, 3, 5, 10, 15 and 20 years were 97%, 82%, 82%, 70%, 62% and
      47%, respectively. The prognosis was more favourable in those with the
      eosinophilic than for the typical variant (there were no cancer-related deaths in
      the former). Of those with the typical variant, five died within 2 years of
      surgery; of these, three with high-stage disease had various degrees of
      sarcomatoid change. Conversely, two patients had a recurrence > 10 years after
      surgery (late recurrence). Both these patients and the others who later died from
      cancer had no sarcomatoid change in the tumour areas examined. CONCLUSION: The
      eosinophilic variant of CCC has a better prognosis; on the contrary, during long
      term surveillance, early recurrence was detected especially in those with
      sarcomatoid change and late recurrence only in two typical variant. These
      prognostic implications of the histological differences are important for
      understanding the outcome of renal CCC.

PMID- 12230611
TI  - Nocturia in relation to sleep, somatic diseases and medical treatment in the
      elderly.
AB  - OBJECTIVE: To assess the influence of somatic diseases, symptoms and medication
      on nocturnal micturition in an elderly population. SUBJECTS AND METHODS: All 10
      216 members of the pensioners' association in two Swedish counties were asked to
      participate in a questionnaire survey. The questions concerned their general
      state of health, occurrence of somatic diseases and symptoms, number of voiding
      episodes per night, and the use of drugs. RESULTS: There were 6143 evaluable
      questionnaires, of which 39.5% were from men. The mean (sd) age of the men and
      women participating were 73.0 (6.0) and 72.6 (6.7) years, respectively. In a
      multivariate logistic model, significant independent correlates of having > or =
      3 nocturnal voids (vs < or = 2 voids) were: being 70-79 years vs < 70 years (odds
      ratio, OR, 1.7, 95% confidence interval, CI, 1.3-2.2), being > or = 80 years old
      vs < 70 years (OR, 1.9, CI, 1.3-2.5) and poor sleep vs good sleep (OR, 2.6, CI,
      2.1-3.2), sequelae after stroke (OR, 2.0, CI, 1.1-3.6), irregular heart beats
      (OR, 1.6, CI, 1.2-2.1) and diabetes (OR, 1.5, CI, 1.1-2.3). Sex, spasmodic chest
      pain and snoring were all deleted by the logistic model. CONCLUSION: Increasing
      age, poor sleep, irregular heart beats, diabetes and stroke are associated with
      an increase in nocturnal micturition in the elderly.

PMID- 12230612
TI  - An audit of urodynamic standardization in the West Midlands, UK.
AB  - OBJECTIVE: To report a follow-up postal survey to one conducted in 1998 assessing
      the feasibility of standardizing urodynamic practice in the West Midlands region.
      METHODS: From the initial survey there was interest in standardizing the practice
      of urodynamics and a few simple guidelines were proposed. The postal survey was
      repeated to identify any changes. The guidelines included zeroing the transducer
      to atmospheric pressure, a filling rate of 50 mL/min and using the International
      Continence Society (ICS) definition of detrusor instability, including numerical
      values and recording any contraction in the presence of urgency. A questionnaire,
      similar to the initial one, was circulated to all the clinicians who had
      participated in the initial study, distributed approximately 8 months after
      agreed guidelines were issued. Specific questions included details of the filling
      and voiding cystometrogram, and the basis of diagnosing detrusor instability.
      They were also asked to comment on whether they would still like the practice to
      be standardized. RESULTS: Only 17 of the 23 clinicians who participated in the
      initial study responded. For zeroing the transducer to atmospheric pressure,
      eight still zeroed to the patient. Only one unit had changed its practice by
      zeroing to atmospheric pressure. Varied rates of filling were still used and only
      eight participants used the ICS criteria to diagnose detrusor instability. Three
      of the 17 participants did not feel that standardization was achievable.
      CONCLUSIONS: Obviously there is some apathy amongst clinicians to move towards
      standardization. No significant changes had been made since standardization
      guidelines were issued. Although most preferred initially to standardize
      urodynamic practice, individuals do not seem to have been convinced that they
      need to change their method to achieve uniformity.

PMID- 12230613
TI  - Sexual function after using tension-free vaginal tape for the surgical treatment
      of genuine stress incontinence.
AB  - OBJECTIVE: To determine whether the use of the tension-free vaginal polypropylene
      tape (TVT) procedure for the treatment of genuine stress incontinence (GSI)
      affects sexual activity. PATIENTS AND METHODS: Sixty-seven women treated by
      insertion of a TVT between September 1998 and March 2001 for GSI were sent
      questionnaires 6-36 months after surgery to determine any urinary symptoms,
      sexual activity, patient satisfaction and the use of hormone-replacement therapy.
      RESULTS: The questionnaire was returned by 57 patients (87%); 43 (76%) reported
      being sexually active and 14 (25%) were not. Of the former, 31 (72%) reported no
      change in sexual function after surgery and only two reported an improvement; six
      (14%) reported that sexual function was worse and four did not reply to the
      questions. The patients reporting that sexual function was worse cited loss of
      libido as the main reason. No patients complained of dyspareunia. CONCLUSIONS:
      There was no significant change in sexual function or activity after the TVT
      procedure and patients can thus be reassured that this operation will not affect
      their sex life.

PMID- 12230614
TI  - The effect of urinary incontinence and overactive bladder symptoms on quality of
      life in young women.
AB  - OBJECTIVE: To assess the consequences that the symptoms of urinary incontinence
      and an overactive bladder have on the quality of life in young, community
      dwelling women. SUBJECTS AND METHODS: A population-based, cross-sectional cohort
      study was conducted in women aged 20-45 years. Urogenital symptoms and quality of
      life were assessed using standardized questionnaires, e.g. the Urogenital
      Distress Inventory and Incontinence Impact Questionnaire. RESULTS: The prevalence
      of symptoms of stress incontinence (39%), urge incontinence (15%) and an
      overactive bladder (12%) was high in this young population. Compared with urge
      incontinence, the symptoms of an overactive bladder similarly reduced the quality
      of life, but stress incontinence did not significantly affect the quality of
      life. Women with symptoms of an overactive bladder were especially limited in
      their mobility, whereas urge incontinence was especially associated with feelings
      of embarrassment. Although many women reported to be bothered by their symptoms,
      only a minority consulted their physician for them. CONCLUSIONS: The symptoms of
      urinary incontinence and overactive bladder are common among young adult women
      and have the same detrimental effect on quality of life as urge incontinence. The
      reduction in mobility associated with overactive bladder symptoms may be
      especially distressing for these young and active women.

PMID- 12230615
TI  - The rectus myofascial wrap in the management of urethral sphincter incompetence.
AB  - OBJECTIVE: To review our experience with a modified rectus/pyramidalis myofascial
      sling, described more than a century ago for treating refractory urinary
      incontinence in children with neurogenic sphincteric incompetence. PATIENTS AND
      METHODS: Thirty-seven patients (23 females and 14 males, aged 8-21 years)
      presented with urinary incontinence which failed to respond to medical treatment.
      In 36 patients the cause of the incontinence was a neurogenic bladder; one
      patient had sustained a traumatic injury to the bladder neck and urethra. Patient
      selection was based on videocysto-urethrographic detection of an incompetent
      bladder neck, and a low maximum closure pressure during urethral pressure
      profilometry. The bladder was augmented in 33 of the 37 patients. RESULTS: Of the
      37 patients, 34 (92%) are dry between catheterizations; the follow-up was 0.5-10
      years. Two of the male patients continued to have persistent incontinence
      requiring bladder neck closure and creation of a continent stoma. One of the
      female patients developed stress incontinence after 4 years of being dry, with a
      rectus sling. CONCLUSION: The rectus myofascial sling provides long-term
      satisfactory dry intervals between catheterizations in patients with neurogenic
      sphincteric incompetence. The cinch-wrap modification appears to enhance the
      occlusive effect of the sling, particularly in males.

PMID- 12230616
TI  - Recurrence and progression in stage T1G3 bladder tumour with intravesical bacille
      Calmette-Guerin (Danish 1331 strain).
AB  - OBJECTIVE: To report recurrence and progression rates in patients with T1G3
      superficial bladder carcinoma treated with intravesical bacille Calmette-Guerin
      (BCG, Danish 1331 strain) after complete transurethral resection. PATIENTS AND
      METHODS: Data from the records of 111 patients with T1G3 bladder carcinoma
      treated between January 1991 and December 1999 were analysed for recurrence,
      progression, salvage therapy and survival. RESULTS: Of the 111 patients with T1G3
      bladder tumours, 69 had intravesical BCG therapy, 20 radical cystectomy and 22
      only transurethral resection (TUR). Of the 69 patients receiving BCG therapy 37
      (54%) had no recurrence, and 24 (35%) had a recurrence that was not muscle
      invasive (Ta/T1) and were treated with TUR only. The remaining eight (12%)
      progressed to muscle invasion and had salvage cystectomy. During the follow-up
      six patients died, four from disease and three from other causes, while the
      remaining 63 are alive and well. Of the other 42 patients, 15 are alive after
      radical cystectomy and 18 after TUR. CONCLUSION: This series further confirms the
      benefits of intravesical BCG (Danish 1331) in an adjuvant setting; furthermore,
      this treatment facilitates bladder preservation by reducing recurrences and
      delaying the progression in many patients.

PMID- 12230617
TI  - Clinical oncologists favour radical radiotherapy for localized prostate cancer: a
      questionnaire survey.
AB  - OBJECTIVE: To explore the treatment preferences of clinical oncologists for
      managing early prostate cancer and to compare the results with the preferences of
      urologists. METHODS: A postal questionnaire survey was conducted of consultant
      clinical oncologists in the UK. RESULTS: Consultant clinical oncologists favour
      radical radiotherapy in most men aged < 70 years, whereas a previous study showed
      that consultant urologists had a greater preference for radical surgery.
      CONCLUSION: There is little consensus about which treatment should be used for
      managing early prostate cancer. There is an urgent need for results from
      randomized clinical trials to determine the optimum treatment.

PMID- 12230618
TI  - Three-month neoadjuvant hormonal therapy before radical prostatectomy: a 7-year
      follow-up of a randomized controlled trial.
AB  - OBJECTIVE: To describe the outcome, assessed as the level of prostate specific
      antigen (PSA), of a mature (more than half the events recorded) prospective
      randomized study with a median follow-up of 82 months of neoadjuvant hormonal
      therapy before radical prostatectomy, as this has been suggested to decrease the
      rate of positive surgical margins (i.e. provide greater potential to completely
      excise the tumour). PATIENTS AND METHODS: From December 1991 to March 1994, 126
      patients with clinically localized prostate cancer were randomized between direct
      radical prostatectomy or a 3-month course of a gonadotrophin-releasing hormone
      analogue before surgery. The patients were followed by PSA determinations and a
      value of > 0.5 ng/mL used to define progression. RESULTS: The incidence of
      positive surgical margins decreased from 45.5% to 23.6% (P = 0.016) with hormone
      treatment. Despite this there was no difference in PSA progression-free survival
      at the last follow-up; it was 51.5% for those undergoing radical prostatectomy
      only and 49.8% for those who received hormonal pretreatment (P = 0.588).
      CONCLUSIONS: Three months of neoadjuvant hormonal therapy before radical
      prostatectomy offers no benefit to the patient and cannot be recommended for
      routine clinical use.

PMID- 12230619
TI  - (125)Iodine prostate brachytherapy: outcome from the first 100 consecutive
      patients and selection strategies incorporating urodynamics.
AB  - OBJECTIVE: To report the results from the first 100 consecutive patients treated
      with 125I transperineal interstitial prostate brachytherapy between March 1999
      and June 2001, and to determine if the International Prostate Symptom Score
      (IPSS), prostate volume or urodynamic variables correlate with acute morbidity.
      PATIENTS AND METHODS: Patients were assessed prospectively by uroflowmetry, the
      IPSS, a physical examination and transrectal ultrasonography. Of the 100
      patients, 57 had a full urodynamic assessment, 61 presented with lower urinary
      tract symptoms (LUTS), 25 were screen-detected and 14 presented with other
      problems. The IPSS was recorded at 1, 6 and 12 weeks, and then at 3-monthly
      intervals after treatment; significant events, e.g. acute urinary retention (AUR)
      and rectal symptoms, were recorded prospectively; the mean follow-up was 16
      months. RESULTS: No patients were incontinent after treatment. There was a
      temporary deterioration in IPSS in 89% of patients. Peak symptoms occurred at 6
      weeks and a statistically significant deterioration in IPSS persisted until 9
      months, but continued to improve throughout the follow-up. AUR affected seven
      patients, with a further 20 using clean intermittent self-catheterization (CISC)
      for symptoms. In most patients the symptoms resolved spontaneously to the levels
      before treatment, with only two patients requiring surgery for bladder outlet
      obstruction. The IPSS before treatment did not predict urodynamic obstruction.
      Urodynamically unobstructed patients did not require catheterization. By 2 years
      after implantation the mean IPSS was better than before treatment. Five patients
      had mild, transient proctitis. CONCLUSION: Selecting patients with a low prostate
      volume and IPSS is likely to optimize the outcome of brachytherapy. Urodynamic
      studies may be helpful in predicting the risk of AUR and symptoms requiring CISC.
      Despite many patients presenting with LUTS, acute morbidity was no worse than
      that reported in large American series of predominantly screening-detected
      cancers. Prostate brachytherapy is well tolerated and may be safely delivered to
      patients with prostate cancer in the UK.

PMID- 12230620
TI  - The CAG trinucleotide repeat length in the androgen receptor does not predict the
      early onset of prostate cancer.
AB  - OBJECTIVE: To relate the repeat length of the androgen-receptor CAG trinucleotide
      to the age of onset of prostate cancer, stage and grade of disease. PATIENTS AND
      METHODS: After obtaining ethical approval, 265 patients with locally confined or
      locally advanced/metastatic prostate cancer were identified and evaluated for age
      at diagnosis (< 65 years and > 75 years). DNA was extracted from peripheral blood
      lymphocytes and 1 micro g aliquots subjected to polymerase chain reaction using
      fluorescently labelled primers. Samples were then run on an ABI 377 gene scan
      analysis gel with an internal molecular weight marker. The length of the CAG
      repeat was determined by comparing the gene scan product size to samples where
      the CAG repeat length had been quantified using direct sequencing. The Kruskal
      Wallis, Mann-Whitney and Wilcoxon two sample tests were used to analyse the data.
      RESULTS: The mean (range) length of the CAG repeat in the androgen receptor was
      22.2 (10-31) in the younger and 22.5 (16-32) in the older group, and was not
      statistically different. There was no significant association between the CAG
      repeat length and the age of onset of prostate cancer (P = 0.568) or with stage
      (P = 0.577) and grade (P = 0.891) of prostate cancer. CONCLUSION: These results
      suggest that there is no correlation between the androgen receptor CAG repeat
      length and the age of onset, stage and grade of prostate cancer, confirming
      recent doubts from other similar studies of a suggested correlation between
      shorter androgen receptor CAG repeat and early onset and aggressiveness of
      prostate cancer.

PMID- 12230621
TI  - Can the reverse transcriptase-polymerase chain reaction for prostate specific
      antigen and prostate specific membrane antigen improve staging and predict
      biochemical recurrence?
AB  - OBJECTIVE: To evaluate the perioperative gene-specific primed nested reverse
      transcription-polymerase chain reaction (RT-PCR) for prostate-specific antigen
      (PSA) and prostate-specific membrane antigen (PSMA) for staging patients
      undergoing radical prostatectomy and predicting biochemical recurrence. PATIENTS
      AND METHODS: In 80 consecutive patients undergoing radical prostatectomy for
      prostate cancer, blood samples were drawn before, during and 1 and 7 days after
      removing the prostate. After buffy coat and mRNA extraction, gene-specific primed
      nested RT-PCR was performed for PSA, PSMA and glyceraldehyde-3-phosphate
      dehydrogenase mRNA, and Southern blot analysis of the PCR reaction. RESULTS: The
      sensitivity of gene-specific RT-PCR to detect tumour cells was comparable with
      random primed RT-PCR. In the 80 patients the stage distribution was pT1 in two
      (2.5%), pT2 in 30 (37.5%) and > or = pT3 in 48 (60%); the nodal status was pN0 in
      57 (71%), pN1 in 11 (14%) and pN2 in 12 (15%). The gene-specific RT-PCR reaction
      for PSA and PSMA was positive in no patients with pT1, 11 (37%) with pT2 and 23
      (48%) with stage > or = pT3 disease. The result for PSA was positive in 12 (52%)
      and for PSMA in 11 (48%) of those with positive nodal status. Neither gene
      specific RT-PCR for PSA or PSMA was able to predict organ-confined disease (P >
      0.5). After a median (range) follow-up of 37 (11-67) months a biochemical
      recurrence was predicted in 65% of patients by preoperative RT-PCR for both PSA
      and PSMA, with a sensitivity, specificity, positive and negative predictive value
      of 58%, 80%, 87% and 47%, respectively; the assay after surgery predicted a
      recurrence in 73%, with respective values of 68%, 84%, 84% and 57%. CONCLUSIONS:
      Gene-specific primed nested RT-PCR for PSA and PSMA is a sensitive and simple
      assay; it might add substantial information for tumour staging in individual
      patients. RT-PCR before surgery allows the prediction of recurrence in 65% of
      cases and after surgery in 73%.

PMID- 12230622
TI  - Can shoe size predict penile length?
AB  - OBJECTIVE: To establish if the 'myth' about whether the size of a man's penis can
      be estimated from his shoe size has any basis, in fact. SUBJECTS AND METHODS: Two
      urologists measured the stretched penile length of 104 men in a prospective study
      and related this to their shoe size. RESULTS: The median stretched penile length
      for the sampled population was 13 cm and the median UK shoe size was 9 (European
      43). There was no statistically significant correlation between shoe size and
      stretched penile length. CONCLUSION: The supposed association of penile length
      and shoe size has no scientific basis.

PMID- 12230623
TI  - Mechanical properties and innervation of the smooth muscle layers of the urethra
      of greyhounds.
AB  - OBJECTIVE: To investigate the properties of the smooth muscle layers in the
      urethral wall of male and female greyhounds, and to consider their roles in
      continence and micturition. MATERIALS AND METHODS: The distribution and
      innervation of the smooth muscle layers of the prostate capsule and membranous
      urethra of male greyhounds were assessed. Strips of smooth muscle from these
      regions were used to determine the neuropharmacological properties by assessing
      the excitatory and inhibitory responses to nerve stimulation, and the effects of
      blocking agents. These were compared with strips from the proximal urethra and
      from the female urethra. RESULTS: The smooth muscle of the membranous urethra
      comprised 9% of the wall and received its innervation exclusively in branches
      from the pelvic plexus. The cholinergic innervation in the male produced 80% of
      the total contractile response in the longitudinal membranous urethra, 50% in the
      prostate capsule and 13% in the circular muscle of the proximal urethra. In the
      female all areas had poor contractile responses. Inhibitory fibres produced
      relaxation in all parts of male and female urethrae with the major effect caused
      by nitric oxide. Adrenergic nerves contributed to both residual excitation (alpha
      receptors) and inhibition (beta receptors). CONCLUSIONS: The longitudinal smooth
      muscle of the male membranous urethra probably shortens the urethra during
      micturition, through the activity of cholinergic nerves, whereas the circular
      smooth muscle of the proximal urethra, under adrenergic control, may be
      contracted during continence and ejaculation. In the female, the smooth muscle
      plays a minor role.

PMID- 12230624
TI  - Effect of chronic renal failure on the purinergic responses of corpus cavernosal
      smooth muscle in rabbits.
AB  - OBJECTIVE: To examine purinergic relaxation responses in chronic renal failure
      (CRF) in an experimental rabbit model, and thus evaluate the possible involvement
      of the purinergic system in erectile dysfunction with CRF. MATERIALS AND METHODS:
      The relaxant effects of ATP were measured in strips of corpus cavernosum smooth
      muscle taken from control and CRF rabbits. CRF was induced in New Zealand white
      rabbits as previously described. Penises were excised from CRF rabbits 4 weeks
      after inducing uraemia. In an organ bath the strips from controls and CRF rabbit
      corpus cavernosum were pre-contracted with phenylephrine and increasing doses of
      adenosine and ATP added. RESULTS: In the pre-contracted rabbit cavernosal tissue
      the relaxations induced by adenosine and ATP were unchanged in CRF. CONCLUSION:
      The lack of any relaxant effect of adenosine or ATP on the relaxation of
      cavernosal smooth muscle in rabbits with CRF might be because the relaxant
      effects of these agents are endothelium-independent and the endothelial
      purinergic receptor density was unchanged in CRF.

PMID- 12230625
TI  - Tissue reaction of the rabbit urinary bladder to tension-free vaginal tape and
      porcine small intestinal submucosa.
AB  - OBJECTIVES: To compare the histological tissue reactions of urinary bladder in
      close contact with polypropylene mesh tension-free vaginal tape (TVT) or porcine
      small intestinal submucosal (SIS) grafts, as the commercial availability of
      various materials has considerably simplified sling procedures for treating
      urinary incontinence, but erosion and infection after using artificial sling
      materials remain an important concern. MATERIALS AND METHODS: Thirty female New
      Zealand rabbits were randomized to three groups, i.e. group A (TVT, 12 animals),
      group B (SIS, 12) and group C (surgical control, six). Through a laparotomy under
      anaesthesia and an aseptic technique, the bladder was approached at its dome,
      where a 0.5 x 1 cm piece of TVT or SIS was fixed in direct contact with the
      bladder wall. The control group underwent only bladder manipulation with no
      material applied. Half the animals in each group were killed after 6 weeks and
      the other half after 12 weeks. The urinary bladder was harvested and examined
      histologically. RESULTS: The grafts in both groups were characterized by dense
      foreign-body type reactions and were mostly attached loosely to the bladder wall
      by a thin layer of fibrovascular tissue. More importantly, the bladder wall
      reactions showed no inflammation in all 12 animals in group A (TVT) but three of
      them had various grades of fibrosis. There was severe transmural inflammation in
      one animal in group B (SIS); one rabbit had grade I and two had grade II
      fibrosis. The controls, as expected, showed no bladder wall reactions.
      CONCLUSION: In this descriptive analysis of reaction types elicited on the
      urinary bladder by these grafts, both materials appeared to be safe. Although TVT
      elicited fewer and less severe adverse reactions, no statistical conclusions can
      be drawn. The clinical significance of these findings should emerge from long
      term clinical data when they become available.

PMID- 12230626
TI  - Vitamin D receptor-dependent antitumour effects of 1,25-dihydroxyvitamin D3 and
      two synthetic analogues in three in vivo models of prostate cancer.
AB  - OBJECTIVE: To determine the in vitro and in vivo effects of 1,25-dihydroxyvitamin
      D3 (calcitriol) and two newer less hypercalcaemic analogues, EB1089 and CB1093
      (as the use of calcitriol as a therapeutic agent in humans has been limited by
      hypercalcaemia) in three rodent models of prostate cancer. MATERIALS AND METHODS:
      The highly metastatic MAT LyLu Dunning prostate model, PAIII tumours in Lobund
      Wistar rats and LNCaP xenografts in nude mice were used. Vitamin D receptor (VDR)
      expression and binding were assessed in all cell lines. The effects of
      calcitriol, EB1089 and CB1093 on tumour growth, cell cycle and angiogenesis in
      vitro, and growth and serum calcium levels in vivo, were assessed. RESULTS: The
      growth of prostate adenocarcinoma was inhibited by calcitriol, EB1089 and CB1093
      in the Dunning prostate model. Although both analogues increased serum calcium
      levels, the levels were significantly less than in rats treated with calcitriol.
      Tumour growth was also inhibited in male athymic nu/nu mice with LNCaP tumour
      xenografts. PAIII cells failed to express functional VDR and were insensitive to
      calcitriol and its analogues, either in vitro or in vivo. The analogues of
      calcitriol did not inhibit angiogenesis in a rat aorta assay. CONCLUSION: This is
      the first report comparing the actions of calcitriol and its analogues in
      different in vivo models. The results suggest that the newer less hypercalcaemic
      analogues of calcitriol may offer a novel therapeutic option for treating
      prostate cancer. VDR-dependent growth inhibition and not the inhibition of
      angiogenesis is the main mechanism of action of these compounds in vivo.

PMID- 12230627
TI  - Experience with 'capsule sparing' cystoprostadenectomy for orthotopic bladder
      replacement: overcoming the problems of impotence, incontinence and difficult
      urethral anastomosis.

PMID- 12230628
TI  - Hydronephrosis: a rare complication of hepatic haemangiomas.

PMID- 12230629
TI  - Renal cell cancer with a symptomatic heart metastasis.

PMID- 12230632
TI  - Circadian rhythm of glycoprotein secretion in the vas deferens of the moth,
      Spodoptera littoralis.
AB  - BACKGROUND: Reproductive systems of male moths contain circadian clocks, which
      time the release of sperm bundles from the testis to the upper vas deferens (UVD)
      and their subsequent transfer from the UVD to the seminal vesicles. Sperm bundles
      are released from the testis in the evening and are retained in the vas deferens
      lumen overnight before being transferred to the seminal vesicles. The biological
      significance of periodic sperm retention in the UVD lumen is not understood. In
      this study we asked whether there are circadian rhythms in the UVD that are
      correlated with sperm retention. RESULTS: We investigated the carbohydrate-rich
      material present in the UVD wall and lumen during the daily cycle of sperm
      release using the periodic acid-Shiff reaction (PAS). Males raised in 16:8 light
      dark cycles (LD) showed a clear rhythm in the levels of PAS-positive granules in
      the apical portion of the UVD epithelium. The peak of granule accumulation
      occurred in the middle of the night and coincided with the maximum presence of
      sperm bundles in the UVD lumen. These rhythms persisted in constant darkness
      (DD), indicating that they have circadian nature. They were abolished, however,
      in constant light (LL) resulting in random patterns of PAS-positive material in
      the UVD wall. Gel-separation of the UVD homogenates from LD moths followed by
      detection of carbohydrates on blots revealed daily rhythms in the abundance of
      specific glycoproteins in the wall and lumen of the UVD. CONCLUSION: Secretory
      activity of the vas deferens epithelium is regulated by the circadian clock.
      Daily rhythms in accumulation and secretion of several glycoproteins are co
      ordinated with periodic retention of sperm in the vas deferens lumen.

PMID- 12230633
TI  - The liver is a common non-exocrine target in primary Sjogren's syndrome: a
      retrospective review.
AB  - BACKGROUND: The autoimmune destruction of exocrine glands that defines primary
      Sjogren's syndrome (1 degrees SS) often extends to non-exocrine organs including
      the liver. We aimed to determine the prevalence of liver disease in patients with
      1 degrees SS and to evaluate the association of this complication with other non
      exocrine features and serologic markers of autoimmunity and systemic
      inflammation. METHODS: We reviewed 115 charts of patients with 1 degrees SS and
      further analyzed the 73 cases that fulfilled the European Epidemiology Center
      Criteria, seeking evidence for clinical and subclinical liver disease. RESULTS:
      Liver function tests had been determined in 59 of the 73 patients. Of those, 29
      patients (49.1%) had abnormal liver function tests including 20.3% with
      clinically overt hepatic disease. Liver disease was the most common non-exocrine
      feature in this cohort. Risk factors for abnormal liver function tests were
      distributed similarly between the patients with and without liver disease. In 60%
      of patients with abnormal liver function tests no explanation for this
      complication was found except for 1 degrees SS. Liver involvement was
      significantly more common in 1 degrees SS patients who also had evidence of lung,
      kidney and hematological abnormalities. Patients with abnormal liver function
      tests were also more likely to have an elevated sedimentation rate and a positive
      anti-ENA during the course of their disease. CONCLUSION: Liver involvement is a
      common complication in 1 degrees SS. Its presence correlates with systemic
      disease. We consider that this complication should be routinely sought in
      patients with 1 degrees SS, especially when a positive anti-ENA or evidence of
      systemic inflammation is found.

PMID- 12230635
TI  - Acute atrial fibrillation.

PMID- 12230634
TI  - The enhancement of the hyperglycemic effect of S-nitrosoglutathione and S-nitroso
      N-acetylpenicillamine by vitamin C in an animal model.
AB  - BACKGROUND: S-nitrosoglutathione (GSNO) and S-nitroso-N-acetlypenicillamine
      (SNAP) are two of the most common sources of nitric oxide (NO) in the biomedical
      field. Vitamin C has been known to accelerate the decomposition of GSNO and SNAP
      increasing the release and availability of NO which is cytotoxic at non
      physiological concentrations. The study investigates any potential detrimental
      effect of vitamin C and GSNO, vitamin C and SNAP on glucose metabolism in
      normotensive and normoglycemic dogs. RESULTS: The results showed that
      administration of vitamin C (50 mg/kg) and GSNO (35 mg/kg & 50 mg/kg), or vitamin
      C (50 mg/kg) and SNAP (10 mg/kg) to overnight fasted dogs resulted in significant
      elevation of the blood glucose levels, attaining maximum level at the 2.0 or 2.5
      h time point postprandially. The elevated blood glucose levels were due to
      significant reduction in plasma insulin levels in the dogs treated with vitamin C
      and GSNO, or vitamin C and SNAP (P < 0.05). The decreased insulin response was
      associated with significant elevation of nitric oxide produced from GSNO and SNAP
      co-administered with vitamin C, as assessed by plasma nitrate/nitrite levels.
      CONCLUSIONS: The results indicate that enhanced NO release by vitamin C affects
      postprandial blood glucose and plasma insulin levels and the reduced glucose
      tolerance is mainly due to impaired insulin release. The clinical relevance of
      the findings of this study suggest that hypertensive diabetic patients treated
      with GSNO or SNAP, who are on vitamin C supplements may be more predisposed to
      further decrease in their glycemic control.

PMID- 12230636
TI  - Acute myocardial infarction.

PMID- 12230637
TI  - Cardiovascular disorders. Changing behaviour.

PMID- 12230638
TI  - Heart failure.

PMID- 12230639
TI  - Peripheral arterial disease.

PMID- 12230640
TI  - Cardiovascular disorders. Primary prevention.

PMID- 12230641
TI  - Secondary prevention of ischaemic cardiac events.

PMID- 12230642
TI  - Stroke management.

PMID- 12230643
TI  - Stroke prevention.

PMID- 12230644
TI  - Thromboembolism.

PMID- 12230645
TI  - Unstable angina.

PMID- 12230646
TI  - Acute gastroenteritis in children.

PMID- 12230647
TI  - Acute otitis media.

PMID- 12230648
TI  - Asthma in children.

PMID- 12230649
TI  - Attention deficit hyperactivity disorder in children.

PMID- 12230650
TI  - Bronchiolitis.

PMID- 12230651
TI  - Cardiorespiratory arrest.

PMID- 12230652
TI  - Constipation.

PMID- 12230653
TI  - Croup.

PMID- 12230654
TI  - Depression in children and adolescents.

PMID- 12230655
TI  - Gastro-oesophageal reflux in children.

PMID- 12230656
TI  - Infantile colic.

PMID- 12230657
TI  - Measles.

PMID- 12230658
TI  - Nocturnal enuresis.

PMID- 12230659
TI  - Recurrent idiopathic epistaxis (nosebleeds).

PMID- 12230660
TI  - Reducing pain during blood sampling in infants.

PMID- 12230661
TI  - Sudden infant death syndrome.

PMID- 12230662
TI  - Urinary tract infection.

PMID- 12230663
TI  - Acute appendicitis.

PMID- 12230665
TI  - Colonic diverticular disease.

PMID- 12230664
TI  - Anal fissure.

PMID- 12230666
TI  - Colorectal cancer.

PMID- 12230667
TI  - Helicobacter pylori infection.

PMID- 12230668
TI  - Stomach cancer.

PMID- 12230669
TI  - Chronic suppurative otitis media.

PMID- 12230670
TI  - Meniere's disease.

PMID- 12230671
TI  - Middle ear pain and trauma during air travel.

PMID- 12230672
TI  - Otitis media with effusion.

PMID- 12230673
TI  - Recurrent tonsillitis.

PMID- 12230674
TI  - Tinnitus.

PMID- 12230675
TI  - Wax in ear.

PMID- 12230676
TI  - Cardiovascular disease in diabetes.

PMID- 12230677
TI  - Foot ulcers and amputations in diabetes.

PMID- 12230678
TI  - Glycaemic control in diabetes.

PMID- 12230679
TI  - Obesity.

PMID- 12230680
TI  - Primary hypothyroidism.

PMID- 12230681
TI  - Acute anterior uveitis.

PMID- 12230682
TI  - Age related macular degeneration.

PMID- 12230683
TI  - Bacterial conjunctivitis.

PMID- 12230684
TI  - Diabetic retinopathy.

PMID- 12230685
TI  - Glaucoma.

PMID- 12230686
TI  - Ocular herpes simplex.

PMID- 12230687
TI  - Trachoma.

PMID- 12230688
TI  - Chickenpox.

PMID- 12230689
TI  - Congenital toxoplasmosis.

PMID- 12230690
TI  - Diarrhoea.

PMID- 12230691
TI  - HIV infection.

PMID- 12230692
TI  - Influenza.

PMID- 12230693
TI  - Lyme disease.

PMID- 12230694
TI  - Malaria in endemic areas.

PMID- 12230695
TI  - Malaria: prevention in travellers.

PMID- 12230696
TI  - Mammalian bites.

PMID- 12230697
TI  - Meningococcal disease.

PMID- 12230698
TI  - Mother to child transmission of HIV.

PMID- 12230699
TI  - Opportunistic infections and HIV.

PMID- 12230700
TI  - Postherpetic neuralgia.

PMID- 12230701
TI  - Tuberculosis.

PMID- 12230702
TI  - Acute renal failure.

PMID- 12230703
TI  - Benign prostatic hyperplasia.

PMID- 12230704
TI  - Chronic prostatitis.

PMID- 12230705
TI  - Erectile dysfunction.

PMID- 12230706
TI  - Prostate cancer: metastatic.

PMID- 12230707
TI  - Prostate cancer: non-metastatic.

PMID- 12230708
TI  - Anorexia nervosa.

PMID- 12230709
TI  - Bulimia nervosa.

PMID- 12230710
TI  - Dementia.

PMID- 12230711
TI  - Depressive disorders.

PMID- 12230712
TI  - Generalised anxiety disorder.

PMID- 12230713
TI  - Obsessive compulsive disorder.

PMID- 12230714
TI  - Panic disorder.

PMID- 12230715
TI  - Post-traumatic stress disorder.

PMID- 12230716
TI  - Schizophrenia.

PMID- 12230717
TI  - Ankle sprain.

PMID- 12230718
TI  - Carpal tunnel syndrome.

PMID- 12230719
TI  - Chronic fatigue syndrome.

PMID- 12230720
TI  - Fracture prevention in postmenopausal women.

PMID- 12230721
TI  - Hallux valgus (bunions).

PMID- 12230722
TI  - Hip fracture.

PMID- 12230723
TI  - Leg cramps.

PMID- 12230724
TI  - Low back pain and sciatica: acute.

PMID- 12230725
TI  - Low back pain and sciatica: chronic.

PMID- 12230726
TI  - Neck pain.

PMID- 12230727
TI  - Non-steroidal anti-inflammatory drugs.

PMID- 12230728
TI  - Osteoarthritis.

PMID- 12230729
TI  - Plantar heel pain (including plantar fasciitis).

PMID- 12230730
TI  - Rheumatoid arthritis.

PMID- 12230731
TI  - Shoulder pain.

PMID- 12230732
TI  - Bell's palsy.

PMID- 12230733
TI  - Chronic tension-type headache.

PMID- 12230734
TI  - Epilepsy.

PMID- 12230735
TI  - Essential tremor.

PMID- 12230736
TI  - Migraine headache.

PMID- 12230737
TI  - Multiple sclerosis.

PMID- 12230738
TI  - Parkinson's disease.

PMID- 12230739
TI  - Trigeminal neuralgia.

PMID- 12230740
TI  - Aphthous ulcers: recurrent.

PMID- 12230741
TI  - Burning mouth syndrome.

PMID- 12230742
TI  - Impacted wisdom teeth.

PMID- 12230743
TI  - Oropharyngeal candidiasis.

PMID- 12230745
TI  - Postoperative pulmonary infections.

PMID- 12230744
TI  - Paracetamol (acetaminophen) poisoning.

PMID- 12230746
TI  - Nausea and vomiting in early pregnancy.

PMID- 12230747
TI  - Perineal care.

PMID- 12230748
TI  - Pre-eclampsia and hypertension.

PMID- 12230749
TI  - Preterm birth.

PMID- 12230751
TI  - Community acquired pneumonia.

PMID- 12230750
TI  - Asthma.

PMID- 12230752
TI  - Lung cancer.

PMID- 12230753
TI  - Spontaneous pneumothorax.

PMID- 12230754
TI  - Upper respiratory tract infection.

PMID- 12230755
TI  - Bacterial vaginosis.

PMID- 12230756
TI  - Genital chlamydial infection.

PMID- 12230757
TI  - Genital herpes.

PMID- 12230758
TI  - Genital warts.

PMID- 12230759
TI  - Gonorrhoea.

PMID- 12230760
TI  - Partner notification.

PMID- 12230761
TI  - Pelvic inflammatory disease.

PMID- 12230762
TI  - Athlete's foot and fungally infected toe nails.

PMID- 12230763
TI  - Atopic eczema.

PMID- 12230764
TI  - Cellulitis and erysipelas.

PMID- 12230765
TI  - Chronic plaque psoriasis.

PMID- 12230766
TI  - Head lice.

PMID- 12230767
TI  - Herpes labialis.

PMID- 12230768
TI  - Malignant melanoma: non-metastatic.

PMID- 12230769
TI  - Non-genital warts.

PMID- 12230770
TI  - Scabies.

PMID- 12230771
TI  - Squamous cell carcinoma of the skin: non-metastatic.

PMID- 12230772
TI  - Wrinkles.

PMID- 12230773
TI  - Sleep apnoea (obstructive sleep apnoea-hypopnoea syndrome).

PMID- 12230774
TI  - Breast cancer: metastatic.

PMID- 12230775
TI  - Breast cancer: non-metastatic.

PMID- 12230776
TI  - Breast pain.

PMID- 12230778
TI  - Endometriosis.

PMID- 12230777
TI  - Dysmenorrhoea.

PMID- 12230779
TI  - Essential vulvodynia (vulval pain).

PMID- 12230780
TI  - Fibroids (uterine myomatosis, leiomyomas).

PMID- 12230781
TI  - Infertility and subfertility.

PMID- 12230782
TI  - Menopausal symptoms.

PMID- 12230783
TI  - Menorrhagia.

PMID- 12230784
TI  - Premalignant vulval disorders.

PMID- 12230785
TI  - Premenstrual syndrome.

PMID- 12230786
TI  - Pyelonephritis in non-pregnant women.

PMID- 12230787
TI  - Recurrent cystitis in non-pregnant women.

PMID- 12230788
TI  - Stress incontinence.

PMID- 12230789
TI  - Vulvovaginal candidiasis.

PMID- 12230790
TI  - Pressure sores.

PMID- 12230791
TI  - Venous leg ulcers.

PMID- 12230793
TI  - Understanding chronic malnutrition in childhood and old age: role of energy
      balance research.
AB  - Undernutrition is commonly associated with chronic disease in children and the
      elderly. Overnutrition is also, but less commonly, associated with chronic
      illness. In most diseases malnutrition arises because energy intake does not
      match energy output. Traditionally, the focus of research has been on
      abnormalities in energy expenditure, in the belief that these factors were the
      main determinants of energy imbalance. Recent studies using the doubly-labelled
      water method to measure total energy expenditure, combined with more complex
      study design, have suggested an alternative conclusion. In many chronic diseases
      patient behaviour, and particularly energy intake, is responsible for energy
      imbalance and malnutrition. Energy balance studies have therefore provided a
      useful foundation for the design of strategies aimed at preventing or managing
      chronic malnutrition. However, modifying patient behaviour is an ambitious
      undertaking which may not be within the scope of existing clinical nutrition
      services. A number of non-traditional models of managing chronic malnutrition in
      children and the elderly are promising. Increasing recognition of the value of
      systematic review will also provide improved strategies for prevention and
      management of chronic malnutrition.

PMID- 12230794
TI  - Modulation of post-operative insulin resistance by pre-operative carbohydrate
      loading.
AB  - Insulin resistance develops as a response to virtually all types of surgical
      stress. There is an increasing body of evidence that suggests that insulin
      resistance in surgical stress is not beneficial for outcome. A recent large study
      in intensive-care patients showed that aggressive treatment of insulin resistance
      using intravenous insulin reduced mortality and morbidity substantially.
      Similarly, in burn patients, intensive insulin and glucose treatment has been
      shown to improve N economy and enhance skin-graft healing. In surgical patients
      insulin resistance has been characterized in some detail, and has been shown to
      have many similarities with metabolic changes seen in patients with type 2
      diabetes. This finding may be important since insulin resistance has been shown
      to be one independent factor that influences length of stay. When patients about
      to undergo elective surgery have been treated with glucose intravenously or a
      carbohydrate-rich drink instead of overnight fasting, insulin resistance was
      reduced by about half. A small meta-analysis showed that when post-operative
      insulin resistance was reduced by pre-operative carbohydrates, length of hospital
      stay was shortened. Overnight intravenous glucose at high doses improved post
      operative N economy. This type of treatment has also been shown repeatedly to
      reduce cardiac complications after open-heart surgery. Furthermore, if the
      carbohydrates are given as a drink pre-operatively, pre-operative thirst, hunger
      and anxiety are markedly reduced. In summary, preventing or treating insulin
      resistance in surgical stress influences outcome. Fasting overnight is not an
      optimal way to prepare patients for elective surgery. Instead, pre-operative
      carbohydrates have clinical benefits.

PMID- 12230795
TI  - Scottish Home Parenteral Nutrition Managed Clinical Network: coordination and
      standards.
AB  - Home parenteral nutrition is required by patients with intestinal disease such
      that they are unable to maintain nutritional status or fluid volume without this
      treatment. A Managed Clinical Network has been established in Scotland. The aims
      of this multi-professional group are to ensure equity of access and that patients
      are managed according to nationally-agreed evidence-based procedures and
      protocols. The Clinical Standards Board for Scotland has provided support in
      preparing a quality-assurance framework to which the network must adhere.

PMID- 12230796
TI  - Effects of fatty acids on gene expression: role of peroxisome proliferator
      activated receptor alpha, liver X receptor alpha and sterol regulatory element
      binding protein-1c.
AB  - Dietary fatty acids have numerous effects on cellular function, many of which are
      achieved by altering the expression of genes. The present paper reviews recent
      data on the mechanisms by which fatty acids influence DNA transcription, and
      focus specifically on the importance of three transcription factors: peroxisome
      proliferator-activated receptor alpha; liver X receptor alpha; sterol regulatory
      element-binding protein 1c. These data indicate that fatty acids induce or
      inhibit the mRNA expression of a variety of different genes by acting both as
      agonists and as antagonists for nuclear hormone receptors.

PMID- 12230797
TI  - 1,25-dihydroxycholecalciferol: endocrinology meets the immune system.
AB  - Previous work has demonstrated that, besides its effects on Ca and bone
      metabolism, the active form of cholecalciferol, 1,25-dihydroxycholecalciferol
      (1,25(OH)2D3), possesses pronounced immunomodulatory effects. In non-obese
      diabetic (NOD) mice primary (before disease onset), secondary (after insulitis
      but before diabetes onset) as well as tertiary (after transplantation of
      syngeneic islets) prevention of diabetes was demonstrated with 1,25(OH)2D3 and
      its chemically-manufactured non-hypercalcaemic analogues. 1,25(OH)2D3 exerts its
      immune effects both at the level of the T lymphocyte (shift in cytokine profile
      from T-helper (Th)1 to Th2, enhanced sensitivity to apoptosis-inducing signals)
      as well as at the level of the antigen-presenting cell (reduced antigen
      presentation, reduced production of Th1-promoting cytokines, reduced expression
      of co-stimulatory molecules). Also, physiologically, 1,25(OH)2D3 is believed to
      have a role in the immune system by serving as a negative feedback signal,
      limiting the mounted immune reaction. To test the clinical applicability of
      1,25(OH)2D3 as treatment for type 1 diabetes in genetically-at-risk young
      children, we tested whether short-term early-life intervention with
      cholecalciferol or non-hypercalcaemic analogues of 1,25(OH)2D3 could prevent
      diabetes in NOD mice. Significant protection of pancreatic beta cells against
      autoimmune destruction was observed in analogue-treated and especially in
      cholecalciferol-treated NOD mice as compared with controls (P<0.005). This short
      term early-life intervention was, however, not able to protect the mice from
      developing diabetes during their lifetime. Possible solutions are longer or
      combined treatments with other immunomodulators that have synergistic effects
      with 1,25(OH)2D3 and its analogues.

PMID- 12230798
TI  - Effects of n-3 fatty acids on cartilage metabolism.
AB  - Although the clinical benefits of dietary supplementation with n-3
      polyunsaturated fatty acids (PUFA) has been recognised for a number of years, the
      molecular mechanisms by which particular PUFA affect metabolism of cells within
      the synovial joint tissues are not understood. This study set out to investigate
      how n-3 PUFA and other classes of fatty acids affect both degradative and
      inflammatory aspects of metabolism of articular cartilage chondrocytes using an
      in vitro model of cartilage degradation. Using well-established culture models,
      cartilage explants from normal bovine and human osteoarthritic cartilage were
      supplemented with either n-3 or n-6 PUFA, and cultures were subsequently treated
      with interleukin 1 to initiate catabolic processes that mimic cartilage
      degradation in arthritis. Results show that supplementation specifically with n-3
      PUFA, but not n-6 PUFA, causes a decrease in both degradative and inflammatory
      aspects of chondrocyte metabolism, whilst having no effect on the normal tissue
      homeostasis. Collectively, our data provide evidence supporting dietary
      supplementation of n-3 PUFA, which in turn may have a beneficial effect of
      slowing and reducing inflammation in the pathogenesis of degenerative joint
      diseases in man.

PMID- 12230799
TI  - Vitamin A as an anti-inflammatory agent.
AB  - Vitamin A is necessary for normal differentiation of epithelial tissues, the
      visual process and reproduction, and is vital for the optimal maintenance and
      functioning of the innate and adaptive immune system. Vitamin A deficiency is one
      of the most profuse nutritional deficiencies worldwide. It is associated with
      increased susceptibility to infectious diseases in both man and animal models.
      Vitamin A also has a role as an anti-inflammatory agent. Supplementation with
      vitamin A has been found to be beneficial in a number of inflammatory conditions,
      including skin disorders such as acne vulgaris, broncho-pulmonary dysplasia and
      some forms of precancerous and cancer states. The present review suggests that
      vitamin A deficiency induces inflammation and aggravates existing inflammatory
      states. Supplementation with vitamin A in selected cases could ameliorate
      inflammation. The two main mechanisms which appear to be involved in the
      prevention of disease are the effects of vitamin A on the immune system and the
      effect on epithelial integrity.

PMID- 12230800
TI  - Regulation of the properties of rat hind limb muscles following gravitational
      unloading.
AB  - The mechanisms responsible for the morphological and metabolic adaptation of
      skeletal muscles to the removal of antigravity activity were investigated in
      rats. Significant atrophy relative to the levels before suspension was induced in
      ankle plantarflexsors, may be due to a reduced tension production caused by
      decreased muscle length and electromyogram activity. Growth failure was
      significant in ankle dorsiflexors, although these muscles did not atrophy. Forced
      muscle contraction through electrical stimulation at 1 or 100 Hz during hind limb
      suspension generally had detrimental effects. The percent contribution of water
      loss to the suspension-related change in weight was 85, 88, and 93% in soleus,
      plantaris, and extensor digitorum longus, respectively. The total levels of both
      beta-hydroxyacyl CoA dehydrogenase (HAD) and lactate dehydrogenase (LDH) were
      less in the suspended muscles than in the controls, having high positive
      correlations with the total protein content. The specific activity of HAD, but
      not of LDH, of the suspended muscles was lower than in the controls (25-61%).
      These data suggest that the cause of muscle atrophy and changes in metabolic
      properties may be a decreased tension development, not necessarily the reduction
      of electrical or contractile activity. Further, it is clearly suggested that
      electrical stimulation of a muscle group with different composition of fiber
      phenotype at a certain pattern or frequency is not suitable for the
      countermeasure. It is also suggested that the major cause of the decreased muscle
      weight was loss of water, even though protein content was also lowered after
      suspension. Moreover, the data suggest that the HAD level was affected more than
      the total protein content and LDH.

PMID- 12230801
TI  - Polymorphisms in control region of mtDNA relates to individual differences in
      endurance capacity or trainability.
AB  - The purpose of this study was to investigate whether the polymorphisms in the
      control region of mitochondrial DNA (mtDNA) related to individual difference in
      the endurance capacity or trainability. Fifty-five sedentary males participated
      in this study and were submitted to an 8-week endurance training program. The
      VO(2 max) was determined before and after training. Total DNA was extracted from
      the blood, and the sequence of the mtDNA control region was determined. The
      polymorphism in the mtDNA control region was decided based on the "Cambridge
      sequence." In 29 of the 55 subjects, vastus lateralis muscle biopsy samples were
      taken at rest before and after the training program. MtDNA content and CS
      (citrate synthase) activity in skeletal muscle was measured as the phenotype of
      the polymorphisms in the mtDNA control region. The VO(2 max) increased to 48.2 +/
      6.3 ml/min/kg from 42.1 +/- 6.0 as a result of the 8-week training (p < 0.05).
      The numbers of polymorphisms in determined 1,122 bp were 11.1 +/- 2.9 variable
      sites per person, and the total numbers of polymorphisms were 125 variable sites.
      The subjects were classified into two groups at each variable site, the Cambridge
      sequence (Cam) group and the non-Cambridge sequence (non-Cam) group. There were
      significant differences in pre-VO(2 max) between the two groups at each mtDNA
      nucleotide positions 16298, 16325, and 199, and in % Delta VO(2 max) at 16223 and
      16362. Twenty-nine subjects who underwent the biopsy revealed significant
      differences in pre-CS activity at 194 and pre-mtDNA content at 514. Also,
      significant differences were found in the change rate of VO(2 max )and CS
      activity as a result of training between the two groups at 16519. In conclusion,
      it suggested that mtDNA polymorphisms in the control region might result in
      individual differences in endurance capacity or trainability.

PMID- 12230802
TI  - Effects of electrical stimulation of the dorsal skin on systemic and mesenteric
      microvascular hemodynamics in anesthetized rats.
AB  - The effects of electrical stimulation of the dorsal skin area on the mesenteric
      arterioles were investigated in anesthetized rats by the use of an intravital
      microscope-television system. Changes in the diameter of the mesenteric
      precapillary arterioles (10-40 microm in diameter) were measured with an image
      processor. Blood flow velocity in the mesenteric precapillary arterioles was
      monitored by the dual sensor method developed by the authors. Electrical
      stimulation was performed through two platinum electrodes placed at the right
      dorsal Th5-12 level skin area by the use of an electrical stimulator (0.2 ms, 20
      Hz). Continuous stimulation lasting for 30 s (1-10 mA) and intermittent
      stimulation lasting for 10 min (3 mA) were applied. The pressor response
      following the depressor response was induced by a stimulus current above 8 mA.
      The decrease in mesenteric blood flow velocity was induced by stimulus current
      above 10 mA. These responses were abolished by lidocaine injection into the
      subcutaneous area where the electrodes were attached. No significant change in
      arteriolar diameter or heart rate were induced by the stimulation for 30 s.
      Electrical stimulation of the skin for 10 min evoked a decrease in the diameter
      of arterioles (-3.4 +/- 2%, p < 0.01, n = 12). In the adrenalectomized group,
      electrical stimulation of the skin for 10 min elicited a slight increase in the
      diameter (1.1 +/- 0.5%, n = 6). It is therefore suggested that electrical
      stimulation of the skin for 30 s reflexly evoked decreases in MAP and in blood
      flow velocity, and that the constriction of the mesenteric precapillary
      arterioles induced by the stimulation for 10 min was mediated by humoral
      adrenaline and noradrenaline released by somato-adrenal medullary reflex.

PMID- 12230803
TI  - Modulation of the Ca2+-activated large conductance K+ channel by intracellular pH
      in human renal proximal tubule cells.
AB  - The Ca2+-activated and voltage-sensitive large conductance K+ channel (BK
      channel) with a slope conductance of about 300 pS is present in the surface
      membrane of cultured human renal proximal tubule epithelial cells (RPTECs). In
      this study we examined the effects of cytoplasmic pH (pH(i)) on activity and
      gating kinetics of the BK channel by using the inside-out configuration of the
      patch-clamp technique. At a constant cytoplasmic Ca(2+) concentration ([Ca2+]i),
      membrane depolarization raised channel open probability (P(o)), and lowering
      pH(i) shifted the P(o)-membrane potential (V(m)) relationship to the positive
      voltage direction. However, the value of the gating charge was not affected by
      changes in pH(i), suggesting that the effects of pH(i) on P(o) were not due to an
      alternation of the voltage sensitivity. At constant V(m), lowering pH(i)
      suppressed the [Ca2+]i-dependent channel activation and shifted the P(o)-[Ca2+]i
      relationship in the direction of higher [Ca2+]i with a reduction of maximal P(o).
      Furthermore, both the mean open and mean closed times of the BK channels at pH(i)
      6.3 in the presence of 10(-4) M [Ca2+](i) were shorter than those at pH(i) 7.3 in
      the presence of 10(-5) M [Ca2+]i, even though these two different conditions gave
      a similar P(o). The data indicate that cytoplasmic H+ suppresses P(o) of the BK
      channel in RPTECs, which involves the mechanism independent of Ca2+ activation.
      Our preliminary kinetic analysis also supported this notion.

PMID- 12230804
TI  - Functional evidence for intracellular acid extruders in human ventricular
      myocardium.
AB  - Intracellular pH (pH(i)) is a major homeostatic system within the cell. Changes
      in pH(i) exert great influence on cardiac contractility and rhythm. Both the
      housekeeping Na+ - H+ exchanger (NHE) and the Na+ - HCO3- symporter (NHS) have
      been confirmed as major transporters for the active acid extrusion mechanism in
      animal cardiomyocytes. However, whether the NHE and NHS functionally coexist in
      human ventricular cardiomyocytes remains unclear. We therefore examined the
      mechanism of pH(i) recovery following an NH4Cl-induced intracellular acidosis in
      the human ventricular myocardium. The pH(i) was monitored by
      microspectrofluorimetry by the use of intracellular 2',7'-bis(2-carboxyethyl)
      5(6)-carboxy-fluorescein (BCECF)-fluorescence. HOE 694 (30 microM), a specific
      NHE inhibitor could block pH(i) recovery from induced intracellular acidosis
      completely in nominally HCO3- -free HEPES Tyrode solution, but it only partially
      inhibited the pH(i) recovery in 5% CO2/HCO3- Tyrode solution. In 5% CO2/HCO3-
      Tyrode solution, the addition of HOE 694 together with DIDS (an NHS inhibitor) or
      the removal of [Na+](o) could entirely inhibit the acid extrusion. We conclude
      for the first time that two different acid extruders, HCO3- -independent and 
      dependent, were most likely the NHE and NHS, respectively, that functionally
      coexisted in the human ventricular cardiomyocytes.

PMID- 12230805
TI  - Development of pressurized retinal resistance-sized arteriolar preparation with
      special reference to acetylcholine-induced nitric-oxide-mediated vasodilatation.
AB  - We examined the responses of pressurized bovine retinal functional arterioles (97
      185 microm in diameter and approximately 3 mm long) to vasoactive substances and
      the mode of action of acetylcholine (ACh) on the pressurized arterioles. The
      retinal arterioles were cannulated at both ends with glass micropipettes and
      perfused at a constant pressure of 60 mmHg. Vasoconstrictions of the retinal
      arterioles were induced by prostaglandin F(2 alpha) (PG F(2 alpha)), U46,619,
      noradrenaline (NA), and 5-hydroxytryptamine (5-HT) in a dose-dependent manner.
      The decreasing order of potency (pD(2) value) in the constrictive responses was
      as follows: 5-HT = U46,619 > NA > PG F(2 alpha). On the other hand, sodium
      nitroprusside (SNP), isocarbacyclin (a stable prostaglandin I(2) analog), ACh,
      and isoproterenol (ISP) caused dose-dependent vasodilatation in the pressurized
      retinal arterioles preconstricted with high-potassium solution (40 mM K+). The
      decreasing order of potency in the vasodilative responses was as follows:
      isocarbacyclin > SNP > ACh. The ACh-induced vasodilatation was suppressed
      significantly by pretreatment with N omega-nitro-L-arginine methyl ester (L-NAME)
      (3 x 10(-5) M). A treatment with L-arginine (10(-3) M) in the presence of 3 x 10(
      5) M L-NAME reversed completely the L-NAME-induced reduction of the
      vasodilatation. These results suggest that ACh causes the production and release
      of endogenous nitric oxide or its related compounds, which results in
      vasodilatation of the pressurized bovine retinal functional arterioles.

PMID- 12230806
TI  - Calcium-activated CL- current is enhanced by acidosis and contributes to the
      shortening of action potential duration in rabbit ventricular myocytes.
AB  - Ca2+-activated Cl- current (I(Cl(Ca))) is activated by Ca2+ transient via Ca2+
      induced Ca2+ release from sarcoplasmic reticulum in cardiac myocytes and is
      supposed to play an important role in the repolarization of action potential. It
      is not well understood, however, how I(Cl(Ca)) is modulated to affect action
      potential in normal or pathological conditions. In this study we examined the
      effects of external acidosis on I(Cl(Ca)) and action potential. A whole-cell
      patch clamp was performed to record action potential and I(Cl(Ca)), using
      isolated rabbit ventricular myocytes. In the standard solution at pH 7.4, action
      potential duration (APD) was markedly prolonged by lowering the extracellular Cl-
      concentration ([Cl-](o)) or by applying an anion channel blocker, 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). In the low pH solution at
      6.4, APD was markedly shortened and the amplitude of I(Cl(Ca)) was increased at
      all membrane potentials. At pH 6.4, the apparent steady-state inactivation curves
      of I(Cl(Ca)) were shifted to more positive potentials compared with those at pH
      7.4, but no change in inactivation occurred at a holding potential of -60 mV. The
      apparent activation curves were not changed between the two sets of conditions.
      When I(Cl(Ca)) was inhibited at low pH, early afterdepolarizations and triggered
      activities were induced. The amplitude of I(Cl(Ca)) was suggested to be enhanced
      by the external acidosis, which may have prevented the induction of early
      afterdepolarization or triggered activity.

PMID- 12230807
TI  - Reassessment of activity-related optical signals in somatosensory cortex by an
      algorithm with wavelength-dependent path length.
AB  - Incorporating the wavelength dependence of the scattering effect into a simple
      linear multicomponent analysis of intrinsic optical signals, we have reexamined
      the change in the hemoglobin (Hb) concentration and the origins of intrinsic
      signals in somatosensory cortex evoked with electrical stimulation of the hind
      limb (5 Hz, 2 s) of anesthetized rat. The concept of the analysis was to separate
      the effect of light scattering involved in the observed optical signals into two
      factors, light attenuation and modification of Hb absorption as a result of the
      wavelength dependence of the optical path length. This dependency was
      experimentally assessed with a tissue-simulating phantom whose absorption spectra
      were nearly identical to those of cerebral tissue through a thinned skull window
      in vivo. Using those phantom spectra, we carried out a curve fitting of the
      reflection spectra from the rat somatosensory cortex activated with an electrical
      stimulation of hind limb (5 Hz, 2 s). Oxygenated Hb slightly decreased at 0.5-1.5
      s after an onset of the stimulus followed by an increase, which peaked at 4 s.
      Deoxygenated Hb increased at 1.0-1.5 s followed by a large late decrease. We
      again confirmed an early increase in the concentration of deoxygenated Hb in the
      rat somatosensory cortex after stimulation of the hind limb.

PMID- 12230808
TI  - Is man able to breathe once a minute for an hour?: the effect of yoga respiration
      on blood gases.
AB  - The ventilatory response to hypercapnia and arterial blood gases during ujjai
      respiration of once per minute for an hour were determined in a professional
      hatha yogi. The results suggest that lower chemosensitivity to hypercapnia in
      yoga practitioners may be due to an adaptation to low arterial pH and high PaCO2
      for long periods.

PMID- 12230809
TI  - Expression of ATP1AL1, a non-gastric proton pump, in human colorectum.
AB  - The expression of mRNAs encoding a human nongastric proton pump (ATP1AL1) in the
      colorectum was investigated. The real-time PCR gave significant levels of signals
      not only in the distal part of human colon and rectum, but also in the proximal
      part of the colon. ATP1AL1 mRNA was overexpressed in 12 out of 20 human
      colorectal adenocarcinomas compared with the level in the accompanying normal
      mucosa. It is noted that astonishing levels of the mRNA overexpression were found
      in 4 carcinomas, which were detected even by Northern blot. The very high levels
      of ATP1AL1 mRNA expression in some cancer tissues may be connected to an unknown
      specific pathophysiological condition.

PMID- 12230810
TI  - Simultaneous estimation of intracellular free Mg2+ and pH by use of a new pH
      dependent dissociation constant of MgATP.
AB  - In the present technical note for 31P-NMR, we used a new pH-dependent
      dissociation constant of MgATP, and re-estimated changes in the intracellular
      free Mg2+ concentration and pH from the chemical shifts of beta- and gamma-ATP
      during Na+-removal in smooth muscle. We confirmed the role of Na+ - Mg2+
      exchange.

PMID- 12230811
TI  - Prognostication in clinical medicine: prophecy or professional responsibility?

PMID- 12230812
TI  - Legal standards for the medical diagnosis and treatment of dementia.

PMID- 12230813
TI  - Medical expert witness bias due to commonality of insurance.

PMID- 12230814
TI  - Children as subjects in nontherapeutic research. Grimes v. Kennedy Krieger
      Institute, Inc.

PMID- 12230817
TI  - Effect of female body weight on efficiency of donor AI.
AB  - A total of 1,144 infertile women were treated by artificial donor insemination.
      Unsuccessful ovulation induction was found in 96 of these cases. The obese women
      (BMI: 28-36) had a relative risk of unsuccessful ovulation induction of 2.7 (95%
      confidence interval (CI) = 2.1-3.4) compared with women lower or normal body
      weight (BMI: 20-24). The effect was smaller in women with a BMI 25-27 or < 19
      (relative risk (RR) = 1.4, 95% CI = 0.9-2.1 and 1.5, 95% CI = 0.8-2.5),
      respectively. During the AID treatment 412 pregnancies occurred. Pregnancy rate
      achieved by insemination was 28% (50 pregnancies per 178 cases, BMI 16-19), 42%
      (251/599, BMI 20-24), 33% (92/286, BMI 25-27), and 21% (19/81, BMI 28-36),
      respectively, in the different BMI groups.

PMID- 12230818
TI  - The scheduled ovarian hyperstimulation method makes it easy to perform ICSI with
      fresh testicular sperm (ICSI/TESE).
AB  - The authors evaluated whether scheduled ovarian stimulation makes it easy to
      perform ICSI with fresh testicular sperm. Scheduled ovarian hyperstimulation was
      applied for testicular sperm extraction and ICSI with fresh testicular
      spermatozoa. Fifteen cycles in 10 couples were included in the present study; all
      couples were azoospermic, 5 were obstructive, and the remaining 5 were
      nonobstructive. No cycles were canceled, and all oocyte retrievals were performed
      on the scheduled day. Testicular sperm were obtained in 14 treatment cycles
      (93%). The mean numbers of retrieved and injected oocytes were 9.4 and 6.4,
      respectively. The fertilization and cleavage rates were 47 and 91%, respectively.
      Embryo transfers were performed in 12 cycles except 2 cycles that had no embryos.
      The number of transferred embryos was 2.3. Two clinical pregnancies were
      obtained. This scheduled ovarian hyperstimulation was applicable for ICSI with
      fresh testicular sperm.

PMID- 12230819
TI  - Mast cells and fibrosis on testicular biopsies in male infertility.
AB  - Testicular dysfunction correlates with increased testicular mast cells. Mast
      cells can activate fibroblasts and promote collagen synthesis. The aim of the
      study was to examine testicular mast cells containing tryptase, and the
      relationship between mast cells and different fibrosis stages of interstitium and
      peritubular region of testes. Testicular biopsies obtained from 33 infertile men
      were assigned to 2 groups: normal spermatogenesis (n = 10) and defective
      spermatogenesis (n = 23). Total, interstitial, and peritubular mast cells were
      examined immunohistochemically using antihuman tryptase. The fibrosis stage was
      evaluated using vimentin and alpha-smooth muscle actin. The ratio of tubules with
      sclerosis to total tubules was also calculated. In all cases, mast cells were
      mainly localized in the interstitium. The number of total mast cells was
      significantly higher in defective spermatogenesis than in normal spermatogenesis
      (p = .048). In both groups, interstitial mast cells were higher than peritubular
      mast cells. However, the increase in peritubular region was much higher than the
      increase in interstitium. Total, peritubular, and interstitial mast cell counts
      were not different from each other, according to the changing fibrosis stages.
      Total and interstitial mast cells were significantly higher in the cases with
      sclerosing seminiferous tubules than in the cases with no sclerosis (p = .04 and
      p = .024, respectively). The mast cells and the mast cell product tryptase could
      be involved in the etiology of defective spermatogenesis, especially whenever the
      last stage (tubular hyalinization and sclerosis) takes place.

PMID- 12230820
TI  - Serum leptin levels in patients with premature ejaculation.
AB  - Leptin is a fat cell-derived hormone signaling the hypothalamus about food
      intake, the regulation of weight, and sexual behavior. The inhibitory effect of
      serotonin on libido, ejaculation, and orgasm is well documented. There is an
      interaction between leptinergic and serotonergic systems in the central nervous
      system. This study was conducted to evaluate serum leptin levels of the patients
      with premature ejaculation. The study group consisted of 15 patients with
      premature ejaculation according to Diagnostic and Statistical Manual of Mental
      Disorders, Third Revised Version (DSM-III-R) and 15 healthy controls. The fasting
      serum leptin levels were measured. Significantly high serum leptin levels in the
      patients were found after body mass index or age adjustment. The intravaginal
      ejaculation latency time negatively correlated with leptin levels in both patient
      and control groups. In addition, there was a positive correlation between leptin
      levels and the duration of illness. It would appear that leptin may be associated
      with premature ejaculation.

PMID- 12230821
TI  - Multiplex sequence-tagged site PCR for efficient screening of microdeletions in Y
      chromosome in infertile males with azoospermia or severe oligozoospermia.
AB  - The multiplex STS-PCR method was used to detect microdeletions in the long arm of
      the Y chromosome (Yq) of cytogenetically normal men. One hundred infertile men
      with azoospermia or oligozoospermia were screened with the multiplex PCR method
      using 58 STSs, which are specific to Yq for detecting microdeletions on this
      chromosome. Correlations between the microdeletions on Yq and phenotypes of
      spermatogenetic disturbance were also examined. Ten patients (10%) had
      microdeletions on Yq. Seven of the 60 azoospermic patients (11.7%), and 3 of the
      40 oligozoospermic patients (7.5%) had microdeletions on Yq. None of the patients
      showed microdeletions in the AZFa region, but 2 had deletions in the AZFb region,
      another 2 in the AZFc region, including DAZ, and 1 had deletions in both the AZFb
      and in the AZFc, including RBM and DAZ. Single microdeletions were found in 4
      patients, all of them in the AZFc around DAZ, and 1 patient had 2 microdeletions
      in the AZFb. The improved multiplex STS-PCR method efficiently detected
      microdeletions in 10% of azoospermic or severe oligozoospermic men who were
      cytogenetically normal. All of these microdeletions were presented in the AZFb
      and/or AZFc regions. This suggests that these regions contain candidate genes for
      spermatogenesis.

PMID- 12230822
TI  - Hypothalmic digoxin, cerebral dominance, and sexual orientation.
AB  - The human hypothalamus produces an endogenous membrane Na(+)-K(+) ATPase
      inhibitor, digoxin. Membrane Na(+)-K(+) ATPase inhibition leads to increase in
      intracellular calcium and upregulated nitric oxide synthesis. In homosexuals,
      promiscuous heterosexuals, and bisexuals there was increased digoxin synthesis,
      reduced membrane Na(+)-K(+) ATPase activity, increased nitric oxide levels,
      increased tryptophan catabolites, and reduced tyrosine catabolites. This pattern
      correlated with that obtained in right hemispheric chemical dominance. In
      nonpromiscuous heterosexuals and left hemispheric chemical dominance there was
      hypodigoxinemia and the reverse biochemical patterns. Hemispheric dominance and
      hypothalamic digoxin could regulate sexual orientation. This has to be viewed in
      the setting of hyperdigoxinemia reported in acquired immunodeficiency syndrome.

PMID- 12230823
TI  - Biphasic effect of GABA on rat sperm acrosome reaction: involvement of GABA(A)
      and GABA(B) receptors.
AB  - The functional relationship between GABA(A) and GABA(B) receptors in regulating
      acrosome reaction (AR) of rat spermatozoa was demonstrated by studying the
      differential effects of a GABA(B) agonist and an antagonist on the process. AR
      rates were determined using the chlortetracycline staining assay. The induction
      of AR in rat sperm by GABA was found to be a biphasic phenomenon; i.e., AR rates
      increased with increasing GABA concentrations up to <5 micro M and at higher
      concentrations of the neurotransmitter (>5 micro M), there was a reductionin the
      AR rates. This biphasic phenomenon is apparently due to the differential
      interaction of the neurotransmitter with GABA receptor subtypes in a dose
      dependent manner; i.e., GABA(A) receptors (stimulatory) are primarily activated
      at low concentration of GABA, while GABA(B) receptors (inhibitory) become
      activated at higher concentrations. This hypothesis is supported by the present
      findings that treatment with saclofen, a GABA(B) receptor antagonist, did not
      influence the AR rates effected by GABA at low concentrations; while the AR rates
      were maintained at the maximum level at higher concentrations of GABA, resulting
      in the elimination of the biphasic phenomenon. Baclofen, a GABA(B) receptor
      agonist, blocks the AR activating action of GABA at both low and high
      concentrations. It would appear that the induction of AR in rat sperm by GABA is
      regulated by the proportionality of activated GABA(A) and GABA(B) receptors
      acting as a yin-yang control.

PMID- 12230824
TI  - Brain nitric oxides synthase in major pelvic ganglia of aged (LETO) and diabetic
      (OLETF) rats.
AB  - This study was conducted to evaluate the effects of aging and diabetes mellitus
      (DM) on brain nitric oxide synthase (bNOS) expression in major pelvic ganglia
      (MPG) of rats. Otsuka Long Evans Tokushima Fatty rats (12, 30, and 70 weeks old),
      which are genetic models with non-insulin-dependent DM (NIDDM), and age-matched
      nondiabetic Long Evans Tokushima Otsuka controls were used. The MPG of all rats
      in this study were subjected to cryo-sectioning and staining with bNOS polyclonal
      AB and rhodamine-conjugated rabbit IgG. Fluorescence intensities of the stained
      neurons were assessed in randomly selected fields per each specimen. Animals of
      both groups revealed significant decline in the staining intensity of their
      neurons with aging and the progress of DM, but diabetic rats showed more decline
      than controls. In conclusion, both aging and NIDDM could decrease bNOS expression
      in rat MPG. However, NIDDM has a more evident effect than aging on that
      expression. The decrease in bNOS may cause a disturbance in functions of the
      target pelvic structures of these ganglia under both conditions.

PMID- 12230825
TI  - Changes in the quality of rabbit semen in 14 consecutive ejaculates obtained
      every 15 minutes.
AB  - Modifications of semen quality related to ejaculation frequency is one of the
      most important and neglected factors from the standpoint of artificial
      insemination or sperm competition. New Zealand white rabbits (Oryctolagus
      cuniculus) offer an advantageous experimental model because they have
      characteristic sexual behavior, they present rapid ejaculation after a single
      intromission, they have a very short interval between successive ejaculations,
      and semen can be easily collected. The authors studied the modifications on sperm
      quality (semen volume, sperm concentration, sperm motility) produced by 14
      consecutive ejaculations recovered every 15 min using stimulus females and an
      artificial vagina. Bucks were exposed every 15 min to a sexually receptive
      female. After each ejaculation the female was removed and reintroduced 15 min
      later. Sperm concentration showed a clear biphasic conduct. The amount of
      spermatozoa per milliliter decreased rapidly until ejaculate number 6, showed a
      highly significant increase in ejaculates 7-9, and decreased to nil in the last 2
      ejaculates. Total number of ejaculated spermatozoa was 557 x 10(6), 76% of which
      were recovered from the first 4 ejaculates. Ejaculate volume also showed a
      biphasic conduct. In the first ejaculates the volume decreased linearly until
      ejaculate number 6, showed a significant increase in ejaculates 7-10, and then
      decreased. The total semen volume recovered during the experiment was 2.44 mL,
      40% of which (0.98 mL) was recovered from the first 2 ejaculates. Individual
      motility in the first 6 ejaculates was preferentially progressive (60% of the
      sperms) and turned to random or in situ from the seventh ejaculate up. The
      proportion of spermatozoa with cytoplasmic droplets increased from ejaculates 6
      and 7 up. The results seem to reflect an acceleration of semen transport through
      the epididymis when the demands for spermatozoa increase.

PMID- 12230826
TI  - Expression of IL-2alpha and IL-2beta receptors on the membrane surface of human
      sperm.
AB  - Cytokines are secreted proteins that act as local immunological mediators.
      Increased seminal cytokine concentrations are associated with fertility problems.
      The purpose of the present study was to investigate the presence of IL-2alpha,
      and IL-2beta receptors on fresh and isolated sperm by flow cytometry and
      transmission electron microscopy. Twenty sperm samples from oligospermic men were
      incubated with CD25, a mouse monoclonal antibody specific for IL-2alpha-chain
      receptor, and CD122, a mouse monoclonal antibody specific for IL-2beta-chain
      receptor. The strong initial fluorescence intensity and, subsequently, a labeling
      index yielded by CD25 and CD122 decreased in sperm centrifuged on a Percoll
      gradient (p < .05). The expression of CD25 and CD122 correlated negatively with
      fresh sperm concentration, but in sperm centrifuged on a Percoll gradient there
      was no correlation. Labeling with CD25 and CD122 antibody was evident on the head
      and the middle piece in fresh sperm, while in sperm centrifuged on a Percoll
      gradient a weak labeling was observed only on the principal piece. The authors
      have identified and localized cytokine receptors on human sperm for the first
      time. Cytokine receptors may be involved in the regulation of pathophysiological
      events in sperm cell functions and male infertility. The exact pathway involved
      in modulation of these receptors requires further investigation. These results
      contribute to the understanding of cytokine-sperm relationships.

PMID- 12230827
TI  - Nightingale revisited.

PMID- 12230828
TI  - Parents' assistance to children having immunizations.
AB  - The purpose of this descriptive study was to determine parents' naturally
      occurring assistive actions when their child received immunizations. Additional
      purposes included describing the preparation the parent provided to the child
      prior to the immunization and parents' plans for assistance following the
      immunization. The convenience sample included 41 parents (or grandparents) of 40
      children between the ages of 18 months and 6 years who were receiving routine
      immunizations at two urban and five rural clinics in the Midwest. Parents were
      interviewed regarding plans to assist their child before and after immunization;
      actual parent-child interactions during immunizations were audiotaped. Data were
      analyzed descriptively; researchers worked in pairs to achieve 100% inter-rater
      agreement when coding observations into themes. The parents reported using nine
      psychological preparation strategies (i.e., procedural information, sensory
      information, relaxation training, telling the child why the procedure was
      necessary, and role play) to assist their children in the preparatory phase.
      Three strategies were used both during (procedural information, distraction, and
      physical contact) and after (physical contact, praise, and rewards) the
      immunization. Ten children received no preparation for the immunization; nine of
      these were younger than 3 years of age. The single most reported source of
      information to parents about helping their child with immunizations was their
      physician.

PMID- 12230829
TI  - Stress in families with medically fragile children.
AB  - The literature related to the stress experienced by families who care for
      medically fragile children is analyzed. A model is generated from themes
      identified in the research literature. Four core themes were identified under
      which most of the stressors identified in the literature could be grouped. These
      are role conflict, financial burden, care burden, and independence. These are in
      turn arranged as a matrix in which the family, the child, the care professional,
      and health care system interact dynamically with the four core themes. The Family
      Stress/Task Matrix has the potential for facilitating research related to models
      that include a family-centered view among health professional and systems.

PMID- 12230830
TI  - Children's injuries in agriculture related events: the effect of supervision on
      the injury experience.
AB  - An international health problem and the leading cause of death and disability
      among children in the United States are unintentional injuries. Children in rural
      areas in the United States have the highest death rate related to unintentional
      injuries regardless of age (Crawley, 1996). Using Haddon's Injury Model as the
      theoretical framework, the purpose of this study is threefold. First the study
      describes actual injuries that were sustained by farm children. Second, the
      research identifies the type of supervision the farm children and adolescents
      were receiving at the time of the injury, and finally the study examines injury
      risk in relation to supervision. Descriptive and categorical data analysis
      methods were used to examine the associations between farm-related injury and
      supervision type. Out of 177 children living in the home under 18 years of age,
      32 children sustained at least one injury and eight sustained two injuries within
      one year from the time of the survey. The majority of children needed medical
      attention because of their injuries (n = 37). Children were more likely to
      sustain farm-related injury when they were supervised by a caregiver engaged in
      farm work versus supervised at home (p =.007). The findings of this study support
      Haddon's Injury Model, which suggests injuries occur because of an uncontrolled
      interaction between a host, an agent, and the environment. Examining the
      children's role within the framework of Haddon's Injury Model, will assist
      researchers in designing evidenced-based research that addresses the interaction
      between the host, agent, and environmental factors. Results from these studies
      will be useful in identifying effective interventions in the pre-event phase, as
      well as maximizing quality of life in the postevent phase.

PMID- 12230831
TI  - Perception of the social support for adolescents who undergo corrective back
      surgery for scoliosis.
AB  - The objective of this study is to compare the perception of social support upon
      admission and 6 weeks postoperation of adolescents aged 13 to 19 years (M = 14.7
      years), who underwent corrective back surgery for scoliosis. Twenty-two French
      speaking participants were found from three different hospital centers located in
      two large cities in the Quebec province. Data were collected using the French
      version of Interpersonal Relationships Inventory (IPRI). No significant
      difference was observed between the results obtained on admission and those
      obtained 6 weeks later for the global measures of social support available.
      Nevertheless, analysis of data at the two time points showed a significant
      difference with regard to intimacy of adolescents. Adolescents reported feeling
      more invaded in the postoperative period (6 weeks after the surgery) than on
      admission at the hospital. These results serve to point out the nursing care
      involvement as well as the surgical techniques and ambulatory care that reduce
      hospitalization time. The results raise questions about the nurse's role in the
      adequate support for adolescents as well as the impact of reduced length of
      hospitalization.

PMID- 12230832
TI  - Memory for centrally attended changing objects in an incidental real-world change
      detection paradigm.
AB  - People often have difficulty detecting visual changes in scenes, a phenomenon
      referred to as 'change blindness'. Although change blindness is usually observed
      in pictures of objects that are not the focus of attention, it also occurs for
      attended objects in the real world. Here, we further explore the finding that
      many participants fail to detect the unexpected substitution of one conversation
      partner for another. We show that change blindness for a conversation partner
      occurs in a variety of situations. Furthermore, when tested with a photographic
      lineup following the change, participants who noticed the substitution showed
      better memory for both pre- and post-change experimenters than participants who
      did not detect the change. We conclude that change blindness in this case is
      associated with relatively ineffective or inaccessible representations of
      previously attended objects, and we contrast these results with others indicating
      that change blindness arises from a failure to compare the original and changed
      object.

PMID- 12230833
TI  - An application of judgment analysis to examination marking in psychology.
AB  - Statistical combinations of specific measures have been shown to be superior to
      expert judgment in several fields. In this study, judgment analysis was applied
      to examination marking to investigate factors that influenced marks awarded and
      contributed to differences between first and second markers. Seven markers in
      psychology rated 551 examination answers on seven 'aspects' for which specific
      assessment criteria had been developed to support good practice in assessment.
      The aspects were: addressing the question, covering the area, understanding,
      evaluation, development of argument, structure and organization, and clarity.
      Principal-components analysis indicated one major factor and no more than two
      minor factors underlying the seven aspects. Aspect ratings were used to predict
      overall marks, using multiple regression to 'capture' the marking policies of
      individual markers. These varied from marker to marker in terms of the numbers of
      aspect ratings that made independent contributions to the prediction of overall
      marks and the extent to which aspect ratings explained the variance in overall
      marks. The number of independently predictive aspect ratings, and the amount of
      variance in overall marks explained by aspect ratings, were consistently higher
      for first markers (question setters) than for second markers. Co-markers' overall
      marks were then used as an external criterion to test the extent to which a
      simple model consisting of the sum of the aspect ratings improved on overall
      marks in the prediction of comarkers marks. The model significantly increased the
      variance in co-markers' marks accounted for, but only for second markers, who had
      not taught the material and had not set the question. Further research is needed
      to develop the criteria and especially to establish the reliability and validity
      of specific aspects of assessment. The present results support the view that, for
      second markers at least, combined measures of specific aspects of examination
      answers may help to improve the reliability of marking.

PMID- 12230834
TI  - A factor-analytic investigation of computer 'addiction' and engagement.
AB  - Evidence supporting the application of Brown's (1991, 1993) conception of
      behavioural addiction to computing behaviour is presented. Questionnaire items
      tapping Brown's addiction criteria were factor-analysed along with others,
      including computer apathy-engagement and computer anxiety-comfort items of
      Charlton and Birkett (1995). Items relating to some of Brown's criteria
      (tolerance, euphoria, and cognitive salience) were found to be complex, an
      Addiction factor loading upon them but an Engagement factor loading more highly.
      Items tapping other criteria (conflict, withdrawal, behavioural salience, and
      relapse and reinstatement) were shown to be factor pure, with only the addiction
      factor loading highly upon them. It is concluded that Brown's conception of
      behavioural addiction can be applied to computer-related behaviour, although the
      relationship of milder facets of addiction, which are also merely indicative of
      high engagement, to computer-related addictions is non-unique. It is also
      concluded that classifying individuals as exhibiting pathological computer use
      using checklists based upon adaptations of DSM criteria for pathological gambling
      is likely to overestimate the number of people addicted to computing activities.

PMID- 12230835
TI  - Deductive reasoning from uncertain conditionals.
AB  - This paper begins with a review of the literature on plausible reasoning with
      deductive arguments containing a conditional premise. There is concurring
      evidence that people presented with valid conditional arguments such as Modus
      Ponens and Modus Tollens generally do not endorse the conclusion, but rather find
      it uncertain, in case (1) the plausibility of the major conditional premise is
      debatable, (2) the major conditional premise is formulated in frequentist or
      probabilistic terms, or (3) an additional premise introduces uncertainty about
      the major conditional premise. This third situation gives rise to non-monotonic
      effects by a mechanism that can be characterized as follows: the reasoner is
      invited to doubt the major conditional premise by doubting the satisfaction of a
      tacit condition, which is necessary for the consequent to occur. Three
      experiments are presented. The first two aim to generalize the latter result
      using various types of conditionals and the last shows that performance in
      conditional reasoning is significantly affected by the representation of the
      task. This third point is discussed along with various other issues: we propose a
      pragmatic account of how the tacit conditions mentioned earlier are treated in
      plausible reasoning; the relationship of this account with the conditional
      probability view on conditional sentences is examined; an application of the same
      account to the Suppression Effect (Byrne, 1989) is proposed and compared with the
      counter-example availability explanation; and finally, some suggestions on how
      uncertainty could be implemented in a mental logic system are presented.

PMID- 12230836
TI  - Some long-term effects of emotion on cognition.
AB  - This study explored the long-term effects of emotion on cognition and over a 12
      day period. Two divergent tasks were employed: a word association task and a
      visual learning task. Over the initial 4 days of the study, participants went
      through a mood-induction procedure then subsequently completed both tasks. Both
      tasks showed a reduction in reaction time consistent with the power law of
      learning across the first 4 consecutive days, and there was no significant change
      in reaction time between day 4 and day 5 (1 week later), suggesting that the
      change in reaction time was robust. The slopes of the power curves are discussed
      in relation to attentional and mnemonic systems that may underlie the observed
      differences in the exponents of the power curves by emotion group.

PMID- 12230837
TI  - Age variations in judgments of 'great' art works.
AB  - This paper reports the results of two large-scale surveys concerning nominations
      of 'greatness' in the arts. In Study 1, 1088 respondents to a national newspaper
      survey nominated the greatest art works of the past 1000 years. Analyses
      indicated that there was some, albeit limited, evidence that older respondents
      nominated older art works, but no evidence of a tendency to nominate works
      produced during the participants' adolescence/early adulthood. In Study 2, a very
      brief questionnaire distributed through a CD retail chain, a national newspaper,
      and a national TV station asked 12,502 participants to nominate up to three of
      the greatest pop musicians of all time. Analyses indicated a tendency to nominate
      musicians who were successful while the participants themselves were in
      adolescence/early adulthood. These results are discussed in terms of the extent
      to which age can explain judgments of artistic 'greatness' within different art
      forms.

PMID- 12230838
TI  - A comparison of reported levels and expression of anger in everyday and driving
      situations.
AB  - Incidents of road rage are frequently reported in the media, yet despite claims
      that aggression on congested roads is a serious social problem, little empirical
      research has explored the question of whether people really do become more
      aggressive behind the wheel. This study compares levels and expression of anger
      in everyday and driving situations with the aim of testing some of the commonly
      held beliefs about aggression on the roads. A survey questionnaire presented 15
      short scenarios describing frustrating situations and included a measure of anger
      and three levels of expression, outward, displaced, and suppressed. The
      questionnaire was posted on the Internet and received 226 responses during a 3
      month period. Analysis revealed that people were no more likely to report
      experiencing anger while driving than in non-driving situations. However, the
      expression of anger did differ in the two contexts. In response to the driving
      scenarios, respondents were significantly more likely to report displacing their
      anger than in non-driving situations. Those individuals who reported high levels
      of anger were also more likely to be outwardly aggressive while driving than they
      were in non-driving situations. Although males and females reported very similar
      levels of anger, their expression of anger did differ. For females, the largest
      difference is between outwardly expressing anger and the other two forms,
      displacing and suppressing, whereas for men, the differences between these three
      forms are more alike. The paper concludes with a discussion of the practical
      implications of these findings.

PMID- 12230839
TI  - Conflict of interest and AJOB.

PMID- 12230840
TI  - How can you patent genes?
AB  - What accounts for the continued lack of clarity over the legal procedures for the
      patenting of DNA sequences? The patenting system was built for a "bricks-and
      mortar" world rather than an information economy. The fact that genes are both
      material molecules and informational systems helps explain the difficulty that
      the patent system is going to continue to have.

PMID- 12230841
TI  - Intellectual property and products of nature.

PMID- 12230842
TI  - Patenting genes and the public interest.

PMID- 12230843
TI  - No patents for semantic information.

PMID- 12230844
TI  - Waiting on science: the stake of present and future patients.

PMID- 12230845
TI  - Locating gene patents within the patent system.

PMID- 12230846
TI  - Patenting genes? A finger in the dike of a bricks-and-mortar patent system.

PMID- 12230847
TI  - Let's get physical.

PMID- 12230848
TI  - Sequence patents are not the issue.

PMID- 12230849
TI  - The evolution of gene patenting.

PMID- 12230850
TI  - Patenting DNA: who defines and protects the public good?

PMID- 12230851
TI  - The two meanings of how and the gene patenting debate.

PMID- 12230852
TI  - Bioterrorism and patent rights: "compulsory licensure" and the case of Cipro.

PMID- 12230853
TI  - Compulsory licensure: the case of Cipro and beyond.

PMID- 12230854
TI  - The Cipro patent and bioterrorism.

PMID- 12230855
TI  - Beyond government intervention: drug companies and bioethics.

PMID- 12230856
TI  - Life, death, and monopoly rights in a democratic society.

PMID- 12230857
TI  - Patents: the public interest versus the private privilege.

PMID- 12230858
TI  - Who are the guardians guarding?

PMID- 12230859
TI  - Patent immorality?

PMID- 12230860
TI  - It is not unethical, though it is often unwise, to override patents.

PMID- 12230861
TI  - Not taking, just borrowing: government use of patented drugs.

PMID- 12230862
TI  - The gift of life and starfish on the beach: the ethics of organ procurement.

PMID- 12230866
TI  - Heme oxygenase-1: past, present, and future.

PMID- 12230867
TI  - Heme oxygenase-1 reduces murine monocrotaline-induced pulmonary inflammatory
      responses and resultant right ventricular overload.
AB  - Monocrotaline (MT), a pyrrolizidine alkaloid, causes pulmonary hypertension (PH)
      in rats and is widely utilized to analyze the pathophysiology of PH. However, a
      murine PH model with which transgenic animals may be used has not been
      established. To establish a murine MT-induced PH model, we administered different
      amounts of MT and determined the extent of right ventricular (RV) overload and
      PH. We also examined the expression of heme oxygenase-1 (HO-1), a potential
      antistress protein in MT-treated animals, and evaluated the functional role of HO
      1 by administering an HO-1 inhibitor. Significant pulmonary inflammation and RV
      hypertrophy were observed when mice were given 600 mg/kg weight of MT weekly for
      8 weeks. In addition, elevated RV pressure and induction of HO-1 in lung and RV
      were observed with this dose of MT. Interestingly, inhibition of HO activity
      promoted inflammatory changes in the lung and the resultant RV hypertrophy. HO-1
      may play defensive roles against murine MT-induced pulmonary inflammation and the
      resultant RV overload.

PMID- 12230868
TI  - Modulation of the thioredoxin system during inflammatory responses and its effect
      on heme oxygenase-1 expression.
AB  - Heme oxygenase (HO) enzymes catalyze the initial reaction in heme catabolism. HO
      1 is an inducible isoform that is up-regulated by diverse stimuli, including
      inflammatory cytokines and factors that promote oxidative stress. HO-1 is a
      cytoprotective enzyme that degrades heme, a potent oxidant, to generate carbon
      monoxide, biliverdin (subsequently reduced to bilirubin), and iron. Recently, we
      found that thioredoxin (TRX), a disulfide reductase enzyme known to be important
      for the binding of transcription factors to DNA, contributes to the induction of
      HO-1 by inflammatory mediators. In the present study, we extended this
      observation and determined that, similar to HO-1, TRX and TRX reductase (TR) are
      induced by bacterial lipopolysaccharide in macrophages at the level of mRNA and
      protein. However, maximal induction of TRX and TR precedes that of HO-1.
      Increased expression of HO-1 in the cytoplasm of inflammatory cells corresponds
      to a translocation of TRX into the nucleus of these cells. Finally, transfection
      of TRX into macrophages promoted an increase in HO-1 protein. Taken together,
      these data support the concept that the TRX system contributes to the up
      regulation of HO-1 under conditions associated with increased oxidative stress.

PMID- 12230870
TI  - Mitogen activated protein kinase (MAPK) pathway regulates heme oxygenase-1 gene
      expression by hypoxia in vascular cells.
AB  - Hypoxia induces the stress protein heme oxygenase-1 (HO-1), which participates in
      cellular adaptation. The molecular pathways that regulate ho-1 gene expression
      under hypoxia may involve mitogen activated protein kinase (MAPK) signaling and
      reactive oxygen. Hypoxia (8 h) increased HO-1 mRNA in rat pulmonary aortic
      endothelial cells (PAEC), and also activated both extracellular signal-regulated
      kinase 1 (ERK1)/ERK2 and p38 MAPK pathways. The role of these kinases in hypoxia
      induced ho-1 gene expression was examined using chemical inhibitors of these
      pathways. Surprisingly, SB203580, an inhibitor of p38 MAPK, and PD98059, an
      inhibitor of mitogen-activated protein kinase kinase (MEK1), strongly enhanced
      hypoxia-induced HO-1 mRNA expression in PAEC. UO126, a MEK1/2 inhibitor, enhanced
      HO-1 expression in PAEC under normoxia, but not hypoxia. Diphenylene iodonium, an
      inhibitor of NADPH oxidase, also induced the expression of HO-1 in PAEC under
      both normoxia and hypoxia. Similar results were observed in aortic vascular
      smooth muscle cells. Furthermore, hypoxia induced activator protein (AP-1) DNA
      binding activity in PAEC. Pretreatment with SB203580 and PD98059 enhanced AP-1
      binding activity under hypoxia in PAEC; UO126 stimulated AP-1 binding under
      normoxia, whereas diphenylene iodonium stimulated AP-1 binding under normoxia and
      hypoxia. These results suggest a relationship between MAPK and hypoxic regulation
      of ho-1 in vascular cells, involving AP-1.

PMID- 12230869
TI  - Effect of prostaglandin-J(2) on VEGF synthesis depends on the induction of heme
      oxygenase-1.
AB  - Heme oxygenase-1 (HO-1) is an inducible enzyme that degrades heme to carbon
      monoxide, iron ions, and biliverdin. Its expression can be induced by 15-deoxy
      Delta(12,14)prostaglandin-J(2) (15d-PGJ(2)), a natural ligand of peroxisome
      proliferator-activated receptor-gamma transcription factor. In macrophages and
      vascular smooth muscle cells, 15d-PGJ(2) up-regulates the expression of vascular
      endothelial growth factor (VEGF), a fundamental regulator of angiogenesis. Here
      we investigated the involvement of HO-1 in the 15d-PGJ(2)-mediated regulation of
      VEGF production by human microvascular endothelial cells (HMEC-1). Resting HMEC-1
      released approximately 20 pg/ml VEGF protein after 24 h of incubation. Treatment
      of cells with 15d-PGJ(2) (1-10 microM) significantly and dose-dependently
      increased the VEGF promoter activity, mRNA expression, and protein secretion. In
      the same cells, 15d-PGJ(2) potently induced the expression of HO-1 protein that
      correlated with HO-1 promoter activity. Activation of HO-1 with hemin or ectopic
      overexpression of HO-1 in HMEC-1 perfectly mimicked the effect of 15d-PGJ(2) and
      led to increased VEGF production. Importantly, the inhibition of the HO-1 pathway
      by tin protoporphyrin-IX significantly reduced the stimulatory effect of 15d
      PGJ(2) on VEGF synthesis. Thus, we postulate that the up-regulation of VEGF
      expression in response to 15d-PGJ(2 )in HMEC-1 is mediated by the activation of
      HO-1.

PMID- 12230871
TI  - Heme degradation and human disease: diversity is the soul of life.
AB  - We all depend on molecular oxygen and heme for our life, as evident from the
      pigments in blood and daily wastes. About 80% of serum bilirubin is derived from
      hemoglobin of senescent erythrocytes, which have finished their mission of 120
      days and have been phagocytized by macrophages in the reticuloendothelial system.
      Here we present an overview of the heme degradation processes and relevant
      disorders by focusing on heme oxygenase-1 (HO-1), a key enzyme in heme
      catabolism. HO-1 cleaves the porphyrin macrocycle of heme at the expense of
      molecular oxygen to release a linear tetrapyrrole biliverdin, carbon monoxide,
      and ferrous iron; biliverdin is rapidly reduced to bilirubin. Bilirubin is
      transported to the liver (hepatocytes), conjugated with glucuronic acid by
      bilirubin UDP-glucuronosyltransferase, and excreted into bile. Genetic diversity,
      a strategy in the host defense, is seen in the human ho-1 and UDP
      glucuronosyltransferase genes. Moreover, striking interspecies variations are
      noted in the regulation of HO-1 expression by hypoxia, heat shock, or interferon
      gamma, each of which mainly represses HO-1 expression in human cells.
      Implications of such a variety are discussed in relevance to the pathogenesis of
      severe malaria caused by Plasmodium falciparum, the most ancient foe of humans.

PMID- 12230872
TI  - Heme oxygenase: evolution, structure, and mechanism.
AB  - Heme oxygenase has evolved to carry out the oxidative cleavage of heme, a
      reaction essential in physiological processes as diverse as iron reutilization
      and cellular signaling in mammals, synthesis of essential light-harvesting
      pigments in cyanobacteria and higher plants, and the acquisition of iron by
      bacterial pathogens. In all of these processes, heme oxygenase has evolved a
      similar structural and mechanistic scaffold to function within seemingly diverse
      physiological pathways. The heme oxygenase reaction is catalytically distinct
      from that of other hemoproteins such as the cytochromes P450, peroxidases, and
      catalases, but shares a hemoprotein scaffold that has evolved to generate a
      distinct activated oxygen species. In the following review we discuss the
      evolution of the structural and functional properties of heme oxygenase in light
      of the recent crystal structures of the mammalian and bacterial enzymes.

PMID- 12230873
TI  - Regulation of heme oxygenase-1 by redox signals involving nitric oxide.
AB  - Heme oxygenase-1 (HO-1) is an inducible stress protein the expression of which
      can be markedly augmented in eukaryotes by a wide range of substances that cause
      a transient change in the cellular redox state. The importance of this protein in
      physiology and disease is underlined by the versatility of HO-1 inducers and the
      functional role attributed to HO-1 products (carbon monoxide and bilirubin) in
      conditions that are associated with moderate or severe cellular stress. An
      intriguing aspect is the recent evidence showing that nitric oxide, a ubiquitous
      signaling molecule, finely modulates the activation of HO-1 expression. As the
      effects of oxidative stress on the regulation of the HO-1 gene have been well
      established and characterized, this review will focus on the biological relevance
      of redox signals involving nitric oxide and reactive nitrogen species that lead
      to up-regulation of the HO-1 pathway, with particular emphasis on vascular
      tissues and the cardiovascular system.

PMID- 12230874
TI  - Heme oxygenase-1: molecular mechanisms of gene expression in oxygen-related
      stress.
AB  - Disturbances of intracellular redox equilibrium may alter eukaryotic gene
      expression patterns in the manifestation of an adaptive stress response. The
      inducible heme oxygenase-1 gene, ho-1, responds dramatically to changes in
      cellular redox potential provoked by multiple agents (oxidants, xenobiotics,
      reactive oxygen species, nitric oxide, and ultraviolet-A radiation) as well as
      deviations in oxygen tension in excess or deficit of normal physiological levels.
      This dual response to hyperoxic and hypoxic states renders ho-1 an intriguing
      model system for studying oxygen-regulated gene expression. The complexation or
      depletion of reduced glutathione apparently represents an underlying mechanism by
      which oxidants trigger the response. Chelatable iron levels also influence the
      induction of ho-1 as evidenced by the inhibitory effects of iron-chelating
      compounds. Redox-sensitive protein kinase cascades (e.g., mitogen-activated
      protein kinases) participate in ho-1 regulation. Recent progress in understanding
      ho-1 transcription has identified two distal enhancer regions (E1, E2) in the
      mouse ho-1 gene that mediate the response to many inducing conditions. This
      review will examine the potential roles of iron, glutathione, and reactive oxygen
      species in the upstream events leading to ho-1 activation following oxygen
      related stress.

PMID- 12230875
TI  - Organ design for generation and reception of CO: lessons from the liver.
AB  - Carbon monoxide (CO) is synthesized in vivo by heme oxygenase. Although for many
      years CO had been regarded as potentially toxic waste, recent studies have
      indicated that it is a signaling molecule with important physiological functions.
      Nitric oxide (NO), another diatomic diffusible gas, is regarded as an established
      signaling molecule. Structural similarities between CO and NO have led many
      investigators to draw analogies between the two gaseous mediators. Whereas the NO
      signaling system has been well defined as to its receptor molecule, soluble
      guanylate cyclase, the CO system has been conceived to require further tuning
      with respect to identifying its receptor molecules and its downstream effectors.
      Furthermore, there has been little quantitative information to argue for a
      physiological role of CO in vivo. This review, therefore, focuses on recent
      developments on both physiologic and pathophysiologic roles of CO in the model of
      isolated perfused liver of rats where endogenous production of CO is actually
      estimated. This model has revealed that CO acts as an endogenous vasorelaxant in
      the liver and that effects of CO are at least in part cyclic GMP-dependent. It
      has also provided answers to many questions of hepatobiliary functions that had
      not been resolved because of the complexity introduced by the interplay between
      NO and CO.

PMID- 12230876
TI  - Heparin-binding EGF-like growth factor (HB-EGF) decreases oxygen free radical
      production in vitro and in vivo.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been
      shown to protect intestinal epithelial cells from anoxia/reoxygenation in vitro,
      and to protect the intestines from ischemia/reperfusion (I/R) injury in vivo. The
      goal of the present study was to determine whether the cytoprotective effects of
      HB-EGF were due, in part, to its ability to decrease reactive oxygen species
      (ROS) production. Human whole blood, polymorphonuclear leukocytes, and monocytes,
      as well as rat intestinal epithelial cells, were exposed to stimuli designed to
      produce an oxidative burst in these cells. Treatment of the cells with HB-EGF led
      to a significant decrease in oxidative burst production. In vivo, total midgut
      I/R injury in rats led to increased ROS production, which was markedly decreased
      by HB-EGF treatment. Histochemically, I/R injury led to increased ROS production,
      which was significantly decreased with HB-EGF treatment. HB-EGF cytoprotection is
      due, in part, to its ability to decrease ROS production. Future studies will
      determine the mechanisms by which HB-EGF exerts these effects.

PMID- 12230877
TI  - Membrane depolarization of isolated rat liver mitochondria attenuates
      permeability transition pore opening and oxidant production.
AB  - It has been suggested that one key feature of mitochondrial permeability
      transition (PT) regulation is its control by the proton electrochemical gradient
      and that depolarization favors pore opening, swelling, and reactive oxygen
      species (ROS) production. Moreover, ROS have been suggested to facilitate the
      process of mitochondrial PT pore opening. The aim of this study was to show that
      collapsing the mitochondrial membrane potential with the mitochondrial uncoupler,
      carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP), at concentrations
      of up to 10 microM, does not induce mitochondrial swelling and, in fact,
      stabilizes mitochondria exposed to oxidant, protecting them from tert-butyl
      hydroperoxide (TBH)-induced high-amplitude swelling. FCCP decreased polyethylene
      glycol-induced mitochondrial contraction following exposure to TBH, indicating
      closing of the PT mega-channel. In the presence of the calcium uniporter
      inhibitor ruthenium red, FCCP induced PT due to suppression of calcium efflux.
      Under PT-favorable conditions, ROS production was evaluated in mitochondria
      following treatments with TBH, inorganic phosphate, or FCCP (with or without
      ruthenium red). FCCP alone and in combination with ruthenium red attenuated
      mitochondria-derived ROS production. FCCP also decreased the augmented ROS
      production induced by inorganic phosphate. It is concluded that mitochondrial
      depolarization protects and prevents high-amplitude swelling and PT-derived ROS
      production.

PMID- 12230879
TI  - Oxidative stress and its role in skin disease.
AB  - Skin is a major target of oxidative stress due to reactive oxygen species (ROS)
      that originate in the environment and in the skin itself. ROS are generated
      during normal metabolism, are an integral part of normal cellular function, and
      are usually of little harm because of intracellular mechanisms that reduce their
      damaging effects. Antioxidants attenuate the damaging effects of ROS and can
      impair and/or reverse many of the events that contribute to epidermal toxicity
      and disease. However, increased or prolonged free radical action can overwhelm
      ROS defense mechanisms, contributing to the development of cutaneous diseases and
      disorders. Although ROS play a role in diseases such as skin cancer, their
      biological targets and pathogenic mode of action are still not fully understood.
      In addition, strategies useful in the therapeutic management of ROS action in
      human skin are still lacking. This review is intended to give investigators an
      introduction to ROS, antioxidants, two skin disorders influenced by ROS action
      (skin cancer and psoriasis), and relevant model systems used to study ROS action.

PMID- 12230878
TI  - Flavonoid antioxidant silymarin and skin cancer.
AB  - Oxidative stress is one of the key players in skin carcinogenesis, and therefore
      identifying nontoxic strong antioxidants to prevent skin cancer is an important
      area of research. In both animal and cell culture studies, we have shown that
      silymarin, a naturally occurring polyphenolic flavonoid antioxidant, exhibits
      preventive and anticancer effects against skin cancer. For example, silymarin
      strongly prevents both photocarcinogenesis and skin tumor promotion in mice, in
      part, by scavenging free radicals and reactive oxygen species and strengthening
      the antioxidant system. We also found that this effect of silymarin is by
      inhibiting endogenous tumor promoter tumor necrosis factor alpha in mouse skin, a
      central mediator in skin tumor promotion. In mechanistic studies, silymarin
      inhibits mitogenic and cell survival signaling and induces apoptosis.
      Furthermore, silymarin effectively modulates cell-cycle regulators and check
      points toward inhibition of proliferation, and growth arrest in G0-G1 and G2-M
      phases of the cell cycle. Thus, due to its mechanism-based chemopreventive and
      anticancer effects in experimental models, silymarin is an important candidate
      for the prevention and/or therapy of skin cancer, as well as other cancers of
      epithelial origin in humans.

PMID- 12230880
TI  - The A640G and C242T p22(phox) polymorphisms in patients with coronary artery
      disease.
AB  - Oxidative stress plays a significant role in the pathogenesis of coronary artery
      disease (CAD). A p22(phox)-based NAD(P)H oxidase acts as a potent superoxide
      generating system in the vasculature. We studied the association of the A640G and
      the C242T polymorphisms with clinical risk factors, endothelial function, and
      severity of CAD in a cohort of 216 patients referred for coronary angiography.
      The frequency of p22(phox) genotypes for AA, AG, and GG was 22.5, 52.3, and
      25.2%, and for CC, CT, and TT 35.5, 51.3, and 13.2%, respectively. The A640G and
      the C242T polymorphisms were not associated with severity of CAD and endothelial
      function. The frequency distribution of the genotypes among patients with or
      without angiographically significant CAD did not reach statistical significance.
      Our study does not support a functional role for the A640G or C242T polymorphisms
      either in the severity of CAD or in determining endothelial function in older
      men.

PMID- 12230881
TI  - Cathepsin B responsiveness to glutathione and lipoic acid redox.
AB  - Some subcomponents of cell protein degradation exhibit an unexplained reductive
      energy requirement; and diverse cysteine proteases are among multiple effector
      mechanisms requiring reduction. Present studies investigated whether cathepsin B
      activity is graded in response to (a) reduced glutathione (GSH) and dihydrolipoic
      acid (DHLA) concentrations, (b) their redox ratios, and (c) their differential
      potencies and efficacies. Purified bovine cathepsin B activity was assayed with
      carbobenzyloxy-Arg-Arg-aminomethylcoumarin by standard methods following
      inactivation by spontaneous air oxidation. Endogenous GSH concentration (2-3 mM)
      maintained 30-40% of the maximal cathepsin B reaction rate observed under
      dithiothreitol (5 mM). Following activation with GSH, the cathepsin B reaction
      rate was inhibited in proportion to nonphysiologic GSH:GSSG redox ratio above 1%
      oxidized (e.g., 85% inhibited at 3 mM:2 mM). Thus, cathepsin B can be redox
      buffered by the GSH:GSSG ratio. DHLA was identified as a potent cathepsin
      activator with threshold near 1 microM and 80% maximal activation near 10 microM.
      Conversely, oxidized lipoamide disulfide inhibited cathepsin B over 5-250 microM.
      DHLA at 5-50 microM superimposed severalfold additional activation upon the
      stable submaximal cathepsin B reaction rate maintained by endogenous GSH
      concentration (2-3 mM). Cell protein degradation was bioassayed by release of
      [3H] leucine from the biosynthetically labeled rat heart under nonrecirculating
      perfusion. The pro-oxidant, diamide (100 microM), reversibly inhibited 80% of
      basal proteolysis. Supraphysiologic extracellular DHLA (80 microM) doubled the
      basal rate of averaged cell protein degradation in 15 min. Thus, the cell redox
      system buffers an intermediate rate of protein degradation, which can be
      decreased by supraphysiologic exposure to diamide pro-oxidant or increased by
      DHLA reductant.

PMID- 12230882
TI  - Overexpression of human thioredoxin in transgenic mice controls oxidative stress
      and life span.
AB  - Transgenic (Tg) mice overexpressing human thioredoxin (TRX), a small redox-active
      protein, were produced to investigate the role of the protein in a variety of
      stresses. Bone marrow cells from TRX-Tg mice were more resistant to ultraviolet C
      induced cytocide compared with those from wild type (WT) C57BL/6 mice. TRX-Tg
      mice exhibited extended median and maximum life spans compared with WT mice.
      Telomerase activity in spleen tissues in TRX-Tg mice was higher than that in WT
      mice. These results suggest that overexpression of TRX results in resistance
      against oxidative stress and a possible extension of life span without apparent
      abnormality in mammals.

PMID- 12230884
TI  - High throughput screening 2002: moving toward increased success rates.

PMID- 12230885
TI  - Application of Micro Arrayed Compound Screening (microARCS) to identify
      inhibitors of caspase-3.
AB  - Micro Arrayed Compound Screening (microARCS) is a miniaturized ultra-high
      throughput screening platform developed at Abbott Laboratories. In this format,
      8,640 discrete compounds are spotted and dried onto a polystyrene sheet, which
      has the same footprint as a 96-well plate. A homogeneous time-resolved
      fluorescence assay format (LANCE) was applied to identify the inhibitors of
      caspase-3 using a peptide substrate labeled with a fluorescent europium chelate
      and a dabcyl quencher. The caspase-3 enzyme was cast into a thin agarose gel,
      which was placed on a sheet containing test compounds. A second gel containing
      caspase substrate was then laid above the enzyme gel to initiate the reaction.
      Caspase-3 cleaves the substrate and separates the europium from the quencher,
      giving rise to a time-resolved fluorescent signal, which was detected using a
      ViewLux charge-coupled device imaging system. Potential inhibitors of caspase-3
      appeared as dark spots on a bright fluorescent background. Results from the
      microARCS assay format were compared to those from a conventional 96-well plate
      screening format.

PMID- 12230886
TI  - Development of a keratinocyte-based screening model for antipsoriatic drugs using
      green fluorescent protein under the control of an endogenous promoter.
AB  - Inflamed epidermis (psoriasis, wound healing, ultraviolet-irradiated skin)
      harbors keratinocytes that are hyperproliferative and display an abnormal
      differentiation program. A distinct feature of this so-called regenerative
      maturation pathway is the expression of proteins such as the cytokeratins CK6,
      CK16, and CK17 and the antiinflammatory protein SKALP/elafin. These proteins are
      absent in normal skin but highly induced in lesional psoriatic skin. Expression
      of these genes can be used as a surrogate marker for psoriasis in drug-screening
      procedures of large compound libraries. The aim of this study was to develop a
      keratinocyte cell line that contained a reporter gene under the control of a
      psoriasis-associated endogenous promoter and demonstrate its use in an assay
      suitable for screening. We generated a stably transfected keratinocyte cell line
      that expresses enhanced green fluorescent protein (EGFP), under the control of a
      0.8-kb fragment derived from the promoter of the SKALP/elafin gene, which confers
      high levels of tissue-specific expression at the mRNA level. Induction of the
      SKALP promoter by tumor necrosis factor-alpha resulted in increased expression
      levels of the secreted SKALP-EGFP fusion protein as assessed by direct readout of
      fluorescence and fluorescence polarization in 96-well cell culture plates. The
      fold stimulation of the reporter gene was comparable to that of the endogenous
      SKALP gene as assessed by enzyme-linked immunosorbent assay. Although the dynamic
      range of the screening system is limited, the small standard deviation yields a Z
      factor of 0.49. This indicates that the assay is suitable as a high-throughput
      screen, and provides proof of the concept that a secreted EGFP fusion protein
      under the control of a physiologically relevant endogenous promoter can be used
      as a fluorescence-based high-throughput screen for differentiation-modifying or
      antiinflammatory compounds that act via the keratinocyte.

PMID- 12230887
TI  - Selective cytotoxicity evaluation in anticancer drug screening of fractionated
      plant extracts.
AB  - Chosen to reflect biodiversity in a phylogenetic sense, 100 fractionated plant
      extracts were screened in vitro for cytotoxicity following extraction and
      fractionation (polypeptide isolation). Of these 100 extracts, 30 were selected
      and then characterized preliminarily for antitumor potency and mode of action by
      testing them on two cell lines and primary cultures of human tumor cells. On the
      basis of cytotoxicity potency, 10 of the extracts were further characterized for
      anticancer activity in 10 human tumor cell lines. This final testing resulted in
      seven potential lead plants with superior evidence of antitumor potential:
      Colchicum autumnale L. (Colchicaceae), Digitalis lanata Ehrh. and Digitalis
      purpurea L. (Plantaginaceae), Helleborus cyclophyllus Boiss. (Ranunculaceae),
      Menyanthes trifoliata L. (Menyanthaceae), and Viola arvensis Murr. and Viola
      patrinii Ging. (Violaceae). Within a database of antitumor compounds, the
      activity profiles of the extracts from these seven plants were compared, by
      correlation analysis, with those of more than 100 other compounds, including 39
      standard drugs from different classes of cytotoxic mechanisms. The activity
      profiles of six of these candidates were uncorrelated with those of the standard
      drugs, possibly indicating new pathways of drug-mediated cell death.

PMID- 12230888
TI  - Outlier mining in high throughput screening experiments.
AB  - A data mining procedure for the rapid scoring of high-throughput screening (HTS)
      compounds is presented. The method is particularly useful for monitoring the
      quality of HTS data and tracking outliers in automated pharmaceutical or
      agrochemical screening, thus providing more complete and thorough structure
      activity relationship (SAR) information. The method is based on the utilization
      of the assumed relationship between the structure of the screened compounds and
      the biological activity on a given screen expressed on a binary scale. By means
      of a data mining method, a SAR description of the data is developed that assigns
      probabilities of being a hit to each compound of the screen. Then, an
      inconsistency score expressing the degree of deviation between the adequacy of
      the SAR description and the actual biological activity is computed. The
      inconsistency score enables the identification of potential outliers that can be
      primed for validation experiments. The approach is particularly useful for
      detecting false-negative outliers and for identifying SAR-compliant hit/nonhit
      borderline compounds, both of which are classes of compounds that can contribute
      substantially to the development and understanding of robust SARs. In a first
      implementation of the method, one- and two-dimensional descriptors are used for
      encoding molecular structure information and logistic regression for calculating
      hits/nonhits probability scores. The approach was validated on three data sets,
      the first one from a publicly available screening data set and the second and
      third from in-house HTS screening campaigns. Because of its simplicity,
      robustness, and accuracy, the procedure is suitable for automation.

PMID- 12230889
TI  - Direct measurement of enzyme activity with infrared spectroscopy.
AB  - A direct approach to enzyme activity measurements is presented. Vibrational
      spectroscopy can monitor the progress of enzymatic reactions because the
      vibrational spectrum of substrates and products usually differs. This is
      demonstrated by the example of ATP hydrolysis by Ca(2+)-ATPase: The substrate
      concentration can be followed using the infrared absorption of the alpha- and
      beta-PO(2)(-) phosphate groups of ATP, and the product concentration can be
      followed using the PO(3)(2-) absorption of P(i) and of the beta-phosphate of ADP.
      The results of the infrared spectroscopic measurement of ATPase activity and of
      an independent activity assay agree very well. The main advantage of the infrared
      method is that it observes the reaction of interest directly--that is, no
      activity assay that converts the progress of the reaction into an observable
      quantity is required.

PMID- 12230890
TI  - A high throughput screen for inhibitors of fungal cell wall synthesis.
AB  - Fungal cell wall synthesis is essential for viability, requiring the activity of
      genes involved in environmental sensing, precursor synthesis, transport,
      secretion, and assembly. This multitude of potential targets, the availability of
      known agents targeting this pathway, and the unique nature of fungal cell wall
      synthesis make this pathway an appealing target for drug discovery. Here we
      describe the adaptation of an assay monitoring cell wall synthesis for high
      throughput screening. The assay requires fungal cell growth, in the presence of
      the test compound, for 3 h before the cells are subjected to osmotic shock in the
      presence of a dye that stains DNA. Miniaturization of the assay to a 384-well
      plate format and removing a mechanical transfer led to subtle changes in the
      assay characteristics. Validation of the assay with a library of known
      pharmacologically active agents has identified a number of different classes of
      compounds that are active in this assay, causing aberrant cell wall morphology
      and in many cases the inhibition of fungal cell growth.

PMID- 12230891
TI  - Development of a plasmepsin II fluorescence polarization assay suitable for high
      throughput antimalarial drug discovery.
AB  - Despite decades of research, malaria remains the world's most deadly parasitic
      disease. New treatments with novel mechanisms of action are urgently needed.
      Plasmepsin II is an aspartyl protease that has been validated as an antimalarial
      therapeutic target enzyme. Although natural products form the basis of most
      modern antimalarial drugs, no systematic high-throughput screening has been
      reported against this target. We have designed an effective strategy for carrying
      out high-throughput screening of an extensive library of natural products that
      uses a fluorescence resonance energy transfer primary screening assay in tandem
      with a fluorescence polarization assay. This strategy allows rapid screening of
      the library coupled with effective discrimination and elimination of false
      positive samples and selection of true hits for chemical isolation of inhibitors
      of plasmepsin II.

PMID- 12230892
TI  - Optimizing higher throughput methods to assess drug-drug interactions for CYP1A2,
      CYP2C9, CYP2C19, CYP2D6, rCYP2D6, and CYP3A4 in vitro using a single point
      IC(50).
AB  - Drug-drug interactions involving cytochrome P(450) (CYP) are an important factor
      in whether a new chemical entity will survive through to the development stage.
      Therefore, the identification of this potential as early as possible in vitro
      could save considerable future unnecessary investment. In vitro CYP interaction
      screening data generated for CYP2C9, CYP2D6, and CYP3A4 were initially analyzed
      to determine the correlation of IC(50) from 10- and 3-point determinations. A
      high correlation (r = 0.99) prompted the further assessment of predicting the
      IC(50) by a single value of percent inhibition at either 10, 3, or 1 microM.
      Statistical analysis of the initial proprietary compounds showed that there was a
      strong linear relationship between log IC(50) and percent inhibition at 3 microM,
      and that it was possible to predict a compound's IC(50) by the percent inhibition
      value obtained at 3 microM. Additional data for CYP1A2, CYP2C19, and the
      recombinant CYP2D6 were later obtained and used together with the initial data to
      demonstrate that a single statistical model could be applicable across different
      CYPs and different in vitro microsomal systems. Ultimately, the data for all five
      CYPs and the recombinant CYP2D6 were used to build a statistical model for
      predicting the IC(50) with a single point. The 95% prediction boundary for the
      region of interest was about +/- 0.37 on log(10) scale, comparable to the
      variability of in vitro determinations for positive control IC(50) data. The use
      of a single inhibitor concentration would enable determination of more IC(50)
      values on a 96-well plate and result in more economical use of compounds, human
      liver or expressed enzyme microsomes, substrates, and reagents. This approach
      would offer the opportunity to increase screening for CYP-mediated drug-drug
      interactions, which may be important given the challenges provided by the
      generation of orders of magnitude more new chemical entities in the field of
      combinatorial chemistry. In addition, the algorithmic approach we propose would
      obviously be applicable for other in vitro bioactivity and therapeutic target
      enzyme and receptor screens.

PMID- 12230894
TI  - Collaborating with academia: what you need to know.

PMID- 12230893
TI  - Development of a high throughput screening assay for mitochondrial membrane
      potential in living cells.
AB  - The mitochondrion plays a pivotal role in energy metabolism in eukaryotic cells.
      The electrochemical potential across the mitochondrial inner membrane is
      regulated to cope with cellular energy needs and thus reflects the bioenergetic
      state of the cell. Traditional assays for mitochondrial membrane potential are
      not amenable to high-throughput drug screening. In this paper, I describe a high
      throughput assay that measures the mitochondrial membrane potential of living
      cells in 96- or 384-well plates. Cells were first treated with test compounds and
      then with a fluorescent potentiometric probe, the cationic-lipophilic dye
      tetramethylrhodamine methyl ester (TMRM). The cells were then washed to remove
      free compounds and probe. The amount of TMRM retained in the mitochondria, which
      is proportional to the mitochondrial membrane potential, was measured on an LJL
      Analyst fluorescence reader. Under optimal conditions, the assay measured only
      the mitochondrial membrane potential. The chemical uncouplers carbonylcyanide m
      chlorophenyl hydrazone and dinitrophenol decreased fluorescence intensity, with
      IC(50) values (concentration at 50% inhibition) similar to those reported in the
      literature. A Z' factor of greater than 0.5 suggests that this cell-based assay
      can be adapted for high-throughput screening of chemical libraries. This assay
      may be used in screens for drugs to treat metabolic disorders such as obesity and
      diabetes, as well as cancer and neurodegenerative diseases.

PMID- 12230897
TI  - Extinction and diversity in alternative medicine.

PMID- 12230898
TI  - Acupuncture: the search for biologic evidence with functional magnetic resonance
      imaging and positron emission tomography techniques.

PMID- 12230899
TI  - Two herbal preparations, Cordyceps Cs4 and Cogent db: do they act on blood
      glucose, insulin sensitivity, and diabetes as "viscous dietary fibers?".

PMID- 12230900
TI  - Arabic medicine: preservation and promotion. A millennium of achievement.

PMID- 12230901
TI  - A pilot study of functional magnetic resonance imaging of the brain during manual
      and electroacupuncture stimulation of acupuncture point (LI-4 Hegu) in normal
      subjects reveals differential brain activation between methods.
AB  - OBJECTIVES: To characterize the brain activation patterns evoked by manual and
      electroacupuncture on normal human subjects. DESIGN: We used functional magnetic
      resonance imaging (fMRI) to investigate the brain regions involved in
      electroacupuncture and manual acupuncture needle stimulation. A block design was
      adopted for the study. Each functional run consists of 5 minutes, starting with 1
      minute baseline and two 1-minute stimulation, the interval between the two
      stimuli was 1 minute. Four functional runs were performed on each subject, two
      runs for electroacupuncture and two runs for manual acupuncture. The order of the
      two modalities was randomized among subjects. During the experiment, acupuncture
      needle manipulation was performed at Large Intestine 4 (LI4, Hegu) on the left
      hand. For each subject, before scanning started, the needle was inserted
      perpendicular to the skin surface to a depth of approximately 1.0 cm.
      Electroacupuncture stimulation was delivered using a continuous rectangular wave
      form (pulse width 30 ms) at a frequency of 3 Hz. For manual acupuncture, the
      needle was rotated manually clockwise and counterclockwise at a rate of about 180
      times per minute (3 Hz). SUBJECTS: Eleven right-handed, normal, healthy volunteer
      adults, 6 male and 5 female, ages 21-64 participated in the experiment. RESULTS:
      Results showed that electroacupuncture mainly produced fMRI signal increases in
      precentral gyrus, postcentral gyrus/inferior parietal lobule, and putamen/insula;
      in contrast, manual needle manipulation produced prominent decreases of fMRI
      signals in posterior cingulate, superior temporal gyrus, putamen/insula.
      CONCLUSION: These results indicate that different brain networks are involved
      during manual and electroacupuncture stimulation. It suggests that different
      brain mechanisms may be recruited during manual and electroacupuncture.

PMID- 12230902
TI  - Assessment of beliefs in the effectiveness of acupuncture for treatment of
      psychiatric symptoms.
AB  - OBJECTIVES: Research has demonstrated that beliefs or expectancies can exert a
      powerful influence on treatment and/or drug effects. As patients participate in
      more complementary and/or alternative treatments for psychiatric conditions, it
      is important to assess the role of belief or expectancy on response to
      nontraditional treatment approaches. The Acupuncture Beliefs Scale was developed
      to assess belief in the efficacy of acupuncture for both physical and psychiatric
      symptoms and conditions. Development and psychometric properties of the scale are
      described. DESIGN AND SUBJECTS: Research personnel solicited statements regarding
      the potential experience and effects of acupuncture. These items were collapsed
      into a set of 36 items, with some rotated to avoid response bias. Outpatients
      diagnosed with bipolar disorder and undergraduates completed the scale (n = 118).
      RESULTS: The scale yielded excellent internal consistency (coefficient alpha =
      0.97), and item-total score correlations between 0.37 and 0.83. Principal
      component analysis with a varimax rotation revealed three significant and
      meaningful factors that were consistent across both subject groups. Factors
      appeared to capture general endorsement of acupuncture treatment, beliefs in the
      scientific value and credibility of acupuncture treatment, and beliefs about the
      procedures and physical experience of acupuncture. CONCLUSIONS: The Acupuncture
      Beliefs Scale is a 36-item self-report scale that may be useful for measurement
      of beliefs in the effectiveness of acupuncture treatment.

PMID- 12230903
TI  - Can the Q Link Ally, a form of Sympathetic Resonance Technology (SRT), attenuate
      acute mobile phone-related changes to neural function?
AB  - OBJECTIVES: Exposure to active mobile phones (MP) has been shown to affect human
      neural function as shown by the electroencephalogram (EEG). Although it has not
      been determined whether such effects are harmful, a number of devices have been
      developed that attempt to minimize these MP-related effects. One such device, the
      Q Link Ally (QL; Clarus Products, International, L.L.C., San Rafael, CA), is
      argued to affect the human organism in such a way as to attenuate the effect of
      MPs. The present pilot study was designed to determine whether there is any
      indication that QL does alter MP-related effects on the human EEG. DESIGN: Twenty
      four (24) subjects participated in a single-blind, fully counterbalanced
      crossover design in which subjects' resting EEG and phase-locked neural responses
      to auditory stimuli were assessed under conditions of either active MP or active
      MP plus QL. RESULTS: The addition of QL to the MP condition increased resting EEG
      in the gamma range and did so as a function of exposure duration, and it
      attenuated MP-related effects in the delta and alpha range (at trend-level). The
      addition of the QL also affected phase-locked neural responses, with a laterality
      reversal in the alpha range and an alteration to changes over time in the delta
      range, a reduction of the MP-related beta decrease over time at fronto-posterior
      sites, and a global reduction in the gamma range that increased as a function of
      exposure duration. No unambiguous relations were found between these changes and
      either performance or psychologic state. CONCLUSIONS: This pilot study suggests
      that the addition of the QL to active MP-exposure does affect neural function in
      humans, altering both resting EEG patterns and the evoked neural response to
      auditory stimuli, and that there is a tendency for some MP-related changes to the
      EEG to be attenuated by the QL.

PMID- 12230904
TI  - Complementary medicine in Israel.
AB  - In recent years, the status of complementary medicine in Israel has appeared
      frequently on the public agenda. The debates and the newspaper headlines
      concerned with this subject usually deal with legal aspects of the subject,
      including the relation between complementary medicine and the medical
      establishment. With the enactment in 1995 of the Compulsory Health Insurance Law,
      debate over the issue intensified, with the public divided over any proposal to
      make complementary medicine part of the services guaranteed by law. This paper
      addresses the current status of complementary medicine in Israel, describes the
      introduction of complementary medicine to Israel, attitudes toward it of both
      consumers and medical professionals, and the question of its legal status. While
      no comprehensive survey describing all aspects of this subject in Israel has yet
      been undertaken, this paper is based on a survey of the professional literature
      in Israel, especially that of the Israeli scientific-medical community, a survey
      of the general press, and an analysis of the health insurance law and its
      position with respect to the complementary medicine.

PMID- 12230905
TI  - A preliminary evaluation of the efficacy and safety of Cogent db (an ayurvedic
      drug) in the glycemic control of patients with type 2-diabetes.
AB  - OBJECTIVES AND STUDY DESIGN: A nonrandomized, non-placebo-controlled clinical
      trial to evaluate the efficacy of Cogent db (an herbal preparation; Cybele Herbal
      Laboratories [PVT] Ltd. Kochi, Kerala State, India) as an adjuvant in the
      treatment of patients with type 2 diabetes was carried out during a 3-month
      period. SETTINGS/LOCATION: This study was conducted in two major peripheral
      clinics of Kuala Lumpur in the Klang Valley, Malaysia. SUBJECTS: A total of 39
      Cogent db-treated cases and 40 age-matched controls were recruited for this
      preliminary study. Nineteen (19) subjects (10 and 9 from control and treatment
      groups, respectively) dropped out of the study leaving a total of 60 subjects (30
      each for control and treatment groups) who completed the study. INTERVENTIONS:
      All subjects in the treatment group were given Cogent db (2 tablets three times
      daily after each meal) in addition to the regular allopathic drugs (Daonil,
      [Aventis Farma, SA Petaling Jaya, Selangor State, Malaysia] and Diamicron
      [Sevier, Bangkok, Thailand], with or without Metformin [Upha Corporation, Bangi,
      Selangor State, India]) that they took in common with the control group. OUTCOME
      MEASURES: Thirty-two (32) clinical variables were investigated, including liver
      enzymes, kidney function tests, hematologic parameters, blood glucose, insulin,
      and C-peptide assays. RESULTS: At the end of 3 months it was found that there was
      a significant decrease in the levels of fasting and postprandial blood glucose,
      cholesterol, triglycerides, glycated hemoglobin (Hb A(1C)) and fasting insulin in
      the treatment group compared to the controls. Cogent db did not alter the liver
      function tests, hematologic parameters, or the kidney function tests.
      CONCLUSIONS: These results concur with earlier animal studies that indicate that
      Cogent db is safe, reliable, tolerable, and efficacious in the control of type 2
      diabetes mellitus.

PMID- 12230906
TI  - Gerimax ginseng regulates both humoral and cellular immunity during chronic
      Pseudomonas aeruginosa lung infection.
AB  - BACKGROUND: Chronic lung infection among patients with cystic fibrosis (CF),
      diffused panbronchiolitis, and chronic obstructive bronchiecteisis is often
      because of Pseudomonas aeruginosa. High morbidity and mortality in patients with
      CF are because of P. aeuruginosa that undergoes genotypic and phenotypic changes
      during prolonged stay in the lung resulting in increased antibiotic resistance,
      necessitating a search for alternative or supplement drugs. OBJECTIVE: In this
      study we compared the therapeutical effect of Gerimax (Dansk Droge A/S, Ishoj,
      Denmark) ginseng with placebo control by using a rat model of chronic P.
      aeruginosa lung infection mimicking that in patients with CF. METHODS AND
      INTERVENTIONS: The animals were challenged intratracheally with the prototypic P.
      aeruginosa PAO1 in alginate beads (1 x 10(9) colony-forming units per milliliter
      [CFU/mL]) followed by subcutaneous injection of ginseng extract (150 mg/kg body
      weight once per day) and examined on days 7 and 21. RESULTS: The day 7 analyses
      show that ginseng treatment resulted in lowering serum immunoglobulin M (IgM) and
      lung interleukin-4 (IL-4) levels compared to the control group. On day 21, higher
      lung IgA, upregulated serum IgG2a, stronger lung responses of interferon-gamma,
      IL-4, and tumor necrosis factor-alpha with milder lung pathology and enhanced
      lung bacteriology were detected in the ginseng-treated group when compared to
      those of the control group. CONCLUSION: These results suggest that the Gerimax
      ginseng treatment can modulate the immune system in favor of clearing the
      infection with P. aeruginosa in the lungs of rats. Thus, ginseng might be a
      promising alternative supplement for the treatment of chronic P. aeruginosa lung
      infection in patients with CF.

PMID- 12230907
TI  - In vitro immunomodulatory effects of ten commonly used herbs on murine
      lymphocytes.
AB  - OBJECTIVES: Physicians are increasingly encountering patients who use herbal
      products. Some of these products are known to modulate the immune system but
      their scientific basic is not well established. Because these products can affect
      the host immune system, they could be beneficial in the treatment of immune
      related diseases, or alternatively, they could cause inadvertent side-effects.
      The purpose of this study was to determine which of these common herbal products
      modulate lymphocyte proliferation in vitro. METHODS: Lymphocyte proliferation
      assays using concanavalin A (mitogen stimulation) and mixed lymphocyte culture
      (alloantigen stimulation) were used as in vitro tests to investigate the
      immunomodulatory effects of 10 commonly used herbal products. RESULTS: Ginger and
      tea were consistently immunosuppressive while dong quai, milk thistle, and St.
      John's wort were consistently immunostimulatory in vitro. Ginseng enhanced
      lymphocyte proliferation only in the mitogen-stimulation assay. The magnitude of
      the enhancement or suppression of the individual herbal products was different in
      the two assays. CONCLUSION: Our study provides a uniform survey of the
      immunomodulatory properties of 10 commonly used herbal products and paves the way
      for testing these effects in vivo and in clinical setting.

PMID- 12230908
TI  - Types of alternative medicine used by patients with breast, colon, or prostate
      cancer: predictors, motives, and costs.
AB  - OBJECTIVE: Assess predictors and costs of various types of alternative medicine
      used by adult patients with cancer. DESIGN, LOCATION, SUBJECTS: Telephone survey
      of 356 patients with colon, breast, or prostate cancer identified from the
      population-based Cancer Surveillance System of western Washington. RESULTS:
      Overall, 70.2% of patients used at least one type of alternative medicine, with
      16.6% seeing alternative providers, 19.1% using mental/other therapy, and 64.6%
      taking dietary supplements. Compared to males, females were five times more
      likely to see an alternative provider and about twice as likely to use mental
      therapies or supplements (p < 0.05 for all). Older patients were less likely to
      use mental/other therapy. Higher education (but not income) was associated with
      use of all types of alternative medicine. Patients with multiple medical
      treatments were two times more likely to take dietary supplements compared to
      patients having only surgery (p < 0.01). Varying by the type of alternative
      therapy, 83%-97% of patients reported that they used alternative medicine for
      general health and well-being while 8% to 56% reported use for treatment of
      cancer. Almost all patients reported that the alternative therapy improved their
      well-being. Expenditures for alternative medicine averaged $68 per user per year,
      but ranged from $4 to $14,659. CONCLUSIONS: Given the high prevalence of use and
      that patients believed that alternative medicine improved their well-being,
      clinicians should show an open mind toward these treatment choices and encourage
      frank discussion. Familiarity and some knowledge regarding use of alternative
      medicine is important in cases where interactions between conventional and
      alternative medicine may occur. It is also important to identify potential
      patient needs for mental health support beyond conventional care and support
      patients who want to make healthful lifestyle changes. Longitudinal
      investigations are urgently needed to investigate associations of alternative
      medicine use with survival and quality of life in patients with cancer.

PMID- 12230909
TI  - Antistress and adaptogenic activity of lecithin supplementation.
AB  - OBJECTIVE: Investigation of lecithin administration in rats for its antistress
      and adaptogenic activity. DESIGN: Lecithin was administered orally (1 mg/g body
      weight) to rats 0.5 hour, 1.5 hours, 3.0 hours, and 6.0 hours prior to cold (5
      degrees C)-hypoxia (428 mm Hg)-restraint (C-H-R) exposure and serum choline
      estimation. The rectal temperature (T(rec)) of the rats was monitored during the
      exposure and the recovery periods. The time for decrease of T(rec) to 23 degrees
      C and its recovery to 37 degrees C were used as indices of antistress and
      adaptogenic activity. RESULTS: Lecithin administration 3-6 hours prior to C-H-R
      exposure was found to have significant adaptogenic activity that correlated with
      increased serum choline levels. Lecithin administration prior to C-H-R exposure
      increased the stress tolerance of the rats by delaying the time for decrease of
      T(rec) to 23 degrees C during C-H-R exposure. It also helped shorten poststress
      recovery as observed by decreased time to attain T(rec) of 37 degrees C from C-H
      R-induced hypothermia (T(rec), 23 degrees C). CONCLUSIONS: The results suggested
      that lecithin supplementation acted as an antistress and adaptogenic functional
      food. It improved resistance during C-H-R exposure and enhanced recovery from
      hypothermia.

PMID- 12230910
TI  - Regression of prostate cancer following administration of Genistein Combined
      Polysaccharide (GCP), a nutritional supplement: a case report.
AB  - PURPOSE: It has been reported that genistein, an isoflavone used in soybeans, has
      antiprostate cancer effects. Genistein Combined Polysaccharide (GCP trade mark;
      AMino Up, Sapporo, Japan), a nutritional supplement manufactured in Japan, is
      composed of genistein and a polysaccharide obtained from basidiomycetes (mycelia)
      that grows in a variety of mushrooms. METHODS: We report a case of a patient with
      a biopsy proven prostate cancer showing clinical and pathologic evidence of
      regression following administration of GCP. The patient was enrolled in an
      Institutional Review Board (IRB)-approved protocol and received GCP for 6 weeks
      prior to radical prostatectomy. RESULTS: The patient's prostate-specific antigen
      (PSA) decreased from an initial value of 19.7 to 4.2 ng/mL after 44 days of low
      dose GCP. No cancer was identified in the radical prostatectomy specimen and no
      side effects were observed in this patient. CONCLUSION: This case suggests that
      GCP, which has shown potent inhibitory effects against prostate cancer in vitro,
      may have some potential activity in the treatment and prevention of prostate
      cancer.

PMID- 12230911
TI  - Teaching evidence-based complementary and alternative medicine: 3. Asking the
      questions and identifying the information.
AB  - Practicing evidence-based complementary and alternative medicine (EBCAM) requires
      skills in accessing current valid literature on clinical queries. This requires
      searching a variety of sources within a broad scope of scientific disciplines.
      This daunting task requires effective skills for accessing information from both
      print and electronic sources. This paper identifies the progression from question
      formulation through to searching and acquiring the valid information. In the
      evolving information age, complementary and alternative medicine (CAM)
      practitioners require informational databases and knowledge of search
      terminology. This paper suggests practical strategies for successful database
      searches in support of EBCAM.

PMID- 12230912
TI  - Introducing integrative East-West medicine to medical students and residents.
AB  - Over the last several years, many medical schools and residencies have introduced
      complementary and alternative medicine (CAM) into their curricula, prompting a
      discussion as to how CAM should be taught. In this paper, we share our
      experiences teaching medical trainees integrative East-West medicine, an approach
      to health and disease that brings together modern Western and Chinese medicine. A
      2-week clinical rotation that is intimately tied to our busy clinical program is
      described in detail as we explore some of the challenges and opportunities
      involved in teaching a CAM-related field to medical trainees. We also demonstrate
      how such a clinical experience offers an opportunity to impart on our students a
      broad view of medicine and to discuss novel approaches to clinical problem
      solving.

PMID- 12230914
TI  - Endotoxin in the environment--exposure and effects.
AB  - This review deals with endotoxin in the environment and its relation to disease
      among exposed persons. Data are presented on levels of endotoxin in different
      environments with maximum values of several microg/m(3). The cellular reactions
      of importance for inhalation exposure effects are attachment to
      lipopolysaccharide binding protein, CD14 cell surface protein and TLR-4
      receptors. The internalisation of endotoxin in macrophages and endothelial cells
      results in local production of inflammatory cytokines with subsequent migration
      of inflammatory cells into the lung and the penetration of cytokines into the
      blood. These events orchestrate clinical effects in terms of toxic pneumonitis,
      airways' inflammation and systemic symptoms. Inhalation challenges with pure
      endotoxin and field studies confirm the relation between these effects and
      exposure to dusts containing endotoxin. It is possible that polymorphism in genes
      determining endotoxin reactivity, particularly TLR-4, influences the risk for
      disease after environmental exposures. Some data suggest that the inflammation
      caused by inhaled endotoxin may decrease the risk for atopic sensitisation among
      children and lung cancer among workers exposed to organic dust. Additional
      research is needed to clarify the role of other environmental agents that are
      present in connection with endotoxin, particularly (1-->3)-beta-D-glucan from
      mold cell walls.

PMID- 12230915
TI  - Staphylococcal enterotoxin B induces hepatic injury and lethal shock in endotoxin
      resistant C3H/HeJ mice despite a deficient macrophage response.
AB  - Bacterial toxins, including endotoxin/LPS as well as superantigens, are major
      causative agents of multi-organ failure associated with sepsis and liver disease.
      However, the precise mechanisms initiating cell activation by the toxins have not
      been clarified. We compared lethal shock and cytokine production in response to
      LPS with responses to the superantigen staphylococcal enterotoxin B (SEB) in both
      LPS-responsive C3H/HeN mice and LPS-hyporesponsive C3H/HeJ mice treated with D
      galactosamine (GalN). LPS was not lethal and did not induce production of TNF
      alpha in C3H/HeJ mice. In contrast, SEB produced lethal shock associated with
      liver failure and induced cytokines such as TNF-alpha, IFN-gamma, and IL-2 in
      both C3H/HeN and C3H/HeJ mice. Peritoneal macrophages from C3H/HeJ mice did not
      produce TNF-alpha in vitro in response to SEB or LPS. However, no significant
      difference was observed in production of TNF-alpha in response to stimulation in
      vitro by SEB between C3H/HeN and C3H/HeJ splenic lymphocytes. We have
      demonstrated that SEB causes lethal toxicity associated with liver injury in LPS
      hyporesponsive C3H/HeJ mice and that as the underlying mechanism, the normal T
      cell function in these mice still maintained the sensitivity to SEB since the
      genetic defect of C3H/HeJ mice unresponsive to LPS and SEB is restricted in
      macrophages/monocytes and does not extend to T cells.

PMID- 12230916
TI  - Lipopolysaccharide binds to and activates A(1) adenosine receptors on human
      pulmonary artery endothelial cells.
AB  - Previously, it was reported that A(1) adenosine receptor antagonists prevent
      endotoxin-induced acute lung injury and pulmonary arterial endothelial cell
      damage. In competition radioligand binding experiments in membranes prepared from
      human pulmonary artery endothelial cells (PAECs), lipopolysaccharides (LPSs) of
      Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae, and Pseudomonas
      aeruginosa displaced the binding of a selective A(1) adenosine receptor
      antagonist [(125)I]-BWA844U (IC(50) values: 195 ng/ml, 290 ng/ml, 602 ng/ml, and
      693 ng/ml, respectively) in a dose-dependent, competitive manner. There was no
      displacement of this radioligand by enterotoxin (< or = 10 microg/ml),
      diphosphoryl lipid A (< or = 10 microg/ml), and glycolipids, monosialoganglioside
      (< or = 1 microg/ml), lactocerebroside (< or = 100 microg/ml), or NBD
      galactocerebroside (< or = 100 microg/ml). Based on calculated IC(50) values, LPS
      (E. coli, IC(50) 111 ng/ml) displaced the selective A(1) adenosine receptor
      agonist, [(3)H]-2-chloro, N(6)-cyclopentyladenosine (CCPA) in human PAECs with a
      potency profile, CCPA > LPS > 2-phenylaminoadenosine (CV 1808), a selective A(2)
      adenosine receptor agonist. The potency profile for displacement of the selective
      A(2a) adenosine receptor agonist [(3)H]-CGS 21680 was CV 1808 > CCPA. LPS (E.
      coli 0.1 pg/ml-10 microg/ml) did not displace [(3)H]-CGS 21680 binding. In human
      PAECs, IL-6 and TXA(2) release induced by LPS (0-1 microg/ml) or CCPA (0-1
      microM) at high doses was significantly reduced by the selective A(1) adenosine
      receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 1 microM). These
      data suggest that LPS binds to and activates A(1) adenosine receptors on human
      PAECs to induce the release of IL-6 and TXA(2). Activation of A(1) adenosine
      receptors on human PAECs by LPS, may contribute to the pathophysiology of acute
      lung injury associated with Gram-negative septicemia and endotoxemia.

PMID- 12230917
TI  - Alterations in membrane-associated CD14 expression and the simultaneous
      liberation of soluble CD14 fragment in adherent macrophages mediated by a
      leukocyte carboxyl/aspartate protease.
AB  - Investigations sought to discover the biochemical mechanisms in macrophages that
      mediate the 'shedding' of soluble CD14 fragment. Stimulated macrophages display
      both increased liberation of soluble CD14 fragment and decreases in residual
      membrane-associated CD14 complexes following exposure to activating agents
      (fMLP/A23187). Application of 'class-specific' protease inhibitors revealed that
      a thiol/cysteine was involved in the biochemical production of soluble CD14
      fractions and that a metalloprotease enzymatically degraded soluble CD14
      fragment. Exposure of macrophages to individual proteases revealed that both
      cathepsin-D and elastase promoted variable depletion of membrane-associated CD14
      complexes. Additionally, cathepsin-D, and to a lesser extent elastase, generated
      soluble CD14 fragment. Related studies isolated a carboxyl/aspartate protease
      from activated macrophages using pepstatin-A affinity chromatography. The
      physical and functional properties of macrophage pepstatin-A binding protein
      fractions closely corresponded with the known characteristics of cathepsin-D with
      respect to: (i) cellular origin; (ii) binding-avidity of carboxyl/aspartate
      proteases for pepstatin-A; (iii) non-specific proteolysis of haemoglobin detected
      by Hb-PAGE zymography; and (iv) hydrolysis of a synthetic cathepsin-D-specific
      peptide substrate. Interpretation of these findings collectively implies that
      activated leukocytes can biochemically alter membrane-associated CD14 complex
      expression and promote the liberation of soluble CD14 fragment in both activated
      and non-activated cell populations.

PMID- 12230918
TI  - The central role of thromboxane and platelet activating factor receptors in ex
      vivo regulation of endotoxin-induced monocyte tissue factor activity in human
      whole blood.
AB  - Expression of tissue factor (TF) by activated monocytes may initiate thrombotic
      episodes associated with diseases, such as thrombosis and atherosclerosis. In
      this study, steps in the regulatory pathways of lipopolysaccharide (LPS)-induced
      monocyte TF activity and released TNF-alpha in human whole blood were probed for
      using an array of inhibitors, comprising specific inhibitors of cytosolic
      phospholipase A(2) (PLA(2)) (AACOCF(3)), secretory PLA(2) (SB-203347), protein
      kinase (PK) (staurosporine), PKC (GF-109203; BIM), and serine protease (Pefabloc
      SC), antagonists of thromboxane prostanoid (TP) receptor (R) (SQ-29548), platelet
      activating factor (PAF) R (BN-52021), leukotriene B(4) R (SC-41930), serotonin R
      (cyproheptadine), fibronectin/fibrinogen R (RGDS), and finally, creatine
      phosphate/creatine phosphokinase (CP/CPK) which removes ADP. Whereas when added
      alone neither of these agents significantly inhibited LPS-induced TF or TNF
      alpha, when presented as a reference cocktail comprising all the agents, TF
      activity and TNF-alpha were reduced by 77% and 49%, respectively. By subsequently
      testing a series of incomplete inhibitory cocktails equal to the reference except
      for deleted single agents or combinations of two or three active agents, the
      inhibitory effect of the reference cocktail could be shown to depend on the
      presence of the protease inhibitor and the thromboxane A(2) and PAF antagonists.

PMID- 12230919
TI  - A novel strategy for the synthesis of neoglycoconjugates from deacylated deep
      rough lipopolysaccharides.
AB  - We report a novel strategy for the preparation of neoglycoconjugates of
      oligosaccharides which are obtained after complete deacylation of bacterial deep
      rough lipopolysaccharides (LPS) isolated from recombinant Escherichia coli
      bacteria synthesizing a Kdo di-[alpha-Kdo-(2-->4)-alpha-Kdo-(2-->] and a Kdo
      trisaccharide [alpha-Kdo-(2-->8)-alpha-Kdo-(2-->4)-alpha-Kdo-(2-->] of Re-type
      and chlamydial LPS, respectively. Unlike acylated LPS, such oligosaccharides can
      be obtained in pure form and thus lead to well-defined neoglycoconjugates.
      Cleavage of the 1-phosphate of the lipid A moiety by alkaline phosphatase
      treatment leads to a free reducing glucosamine which can be further reacted with
      allylamine. After reductive amination, spacer elongation of the allyl group with
      cysteamine and activation with thiophosgene, the ligands were reacted with BSA.
      We have compared the immunological reactivity of such defined neoglycoconjugates
      obtained from natural sources with those obtained by chemical synthesis and
      report that such neoglycoconjugates are immunogenic and well suited as antigens
      for the study of epitope specificities of monoclonal antibodies. In addition, we
      have compared these conjugates with those in which ligands were coupled by
      glutardialdehyde to BSA. Our approach proved to be superior since the latter led
      upon immunization of mice to a relatively high percentage of antibodies that
      reacted with glutardialdehyde derivatized BSA without the carbohydrate ligand.
      This was not the case for cysteamine-spacered ligands coupled via their
      isothiocyanate-derivatives.

PMID- 12230920
TI  - Pretreatment with troglitazone decreases lethality during endotoxemia in mice.
AB  - Troglitazone is an oral antidiabetic drug that is a ligand for peroxisome
      proliferator activated receptor gamma (PPARgamma). Based on other studies that
      have implicated an immunosuppressive role for PPARgamma during inflammatory
      responses, we hypothesized that troglitazone treatment would improve survival in
      a murine model of endotoxemia and that the protective effect would be mediated by
      decreased expression of inflammatory mediators. C57Bl/6N x Sv/129 (wild-type
      [WT]) or PPARalpha null mice treated for 2 weeks with dietary troglitazone (0.1%)
      had significantly fewer deaths and a higher LD(50) value compared to control-fed
      mice when challenged with lipopolysaccharide (LPS). PPARalpha null mice were more
      sensitive to the lethal effects of LPS as evidenced by a 2-fold lower LD(50) (6.6
      mg/kg) compared to WT mice (14.6 mg/kg). Troglitazone treatment had no
      significant effect on LPS-induced plasma TNF, glucose, or nitric oxide levels in
      WT or PPARalpha null mice at any of the time points examined. However,
      troglitazone treatment significantly reduced LPS-induced plasma IL-6 levels in
      both WT and PPARalpha null mice. The results of these studies suggest that
      troglitazone treatment protects mice against a lethal challenge of LPS, but
      whether or not this effect is mediated through decreased expression of
      inflammatory mediators remains unclear.

PMID- 12230921
TI  - Medical management of sexual difficulties in HIV-positive individuals.
AB  - In the current era of effective antiretroviral therapy, sexual dysfunction is
      being increasingly recognized in HIV-positive individuals. This article reviews
      the literature about the causes, treatments available and any issues specific to
      the HIV-positive individual.

PMID- 12230922
TI  - Patient preferences regarding antiretroviral therapy.
AB  - Antiretroviral medications for HIV infection can be combined into dozens of
      recommended regimens. However, little is known about patient preferences
      regarding antiretroviral therapy. We assessed the impact of clinician-mutable
      adherence barriers by conducting four patient focus groups (two English and two
      Spanish) consisting of 30 patients that focused discussion on antiretroviral
      treatment preferences. We also surveyed antiretroviral treatment preference from
      31 subjects using the method of paired comparisons in which subjects indicated
      their preferences of regimen potency, pill burden, inconvenience, and side
      effects using a 10-point rating scale. We found that most patients would tolerate
      severe side-effects, inconvenience, and large pill burden to have a potent
      antiretroviral regimen. In our population, patients generally preferred regimens
      with fewer side-effects to those with less inconvenience. Pill burden was of
      least importance among the domains studied. These preferences should be
      considered when selecting a regimen and developing interventions to improve
      antiretroviral adherence and patient outcomes.

PMID- 12230923
TI  - HIV post-exposure prophylaxis after sexual assault: the experience of a sexual
      assault service in London.
AB  - OBJECTIVES: To review the provision, uptake and outcome of HIV post-exposure
      prophylaxis (HIV-PEP) after sexual assault. METHODS: A retrospective case note
      review of patients attending a sexual assault service in London during 1999.
      RESULTS: Ten out of 150 patients were considered eligible for PEP after a careful
      risk assessment. Eight patients accepted HIV-PEP. Highly active antiretroviral
      therapy (HAART) consisted of Combivir/indinavir in six patients and
      Combivir/nelfinavir in two patients. Two patients changed their combination due
      to adverse events. Five patients completed the recommended 28 days of treatment.
      Three patients discontinued therapy due to adverse events. Two patients who
      completed HIV-PEP were noted to have raised cholesterol at follow-up. All
      patients who took PEP were HIV-1 and -2 antibody negative at six months.
      CONCLUSIONS: Compared with other published studies the completion rate of HIV-PEP
      in our study was high. The uptake and adverse events of HAART in this scenario
      were similar to previously published studies. A multidisciplinary approach to the
      management of this patient group will improve adherence to PEP.

PMID- 12230924
TI  - Laboratory diagnosis of sexually transmitted infections in women with genital
      discharge in Madagascar: implications for primary care.
AB  - Women seeking care in Madagascar for genital discharge (n = 1,066) were evaluated
      for syphilis seroreactivity; bacterial vaginosis (BV) and trichomoniasis.
      Chlamydial infection was assessed by ligase chain reaction (LCR) and by direct
      immunofluorescence (IF); gonorrhoea by direct microscopy, culture and LCR.
      Leucocytes were determined in endocervical smears and in urine using leucocyte
      esterase dipstick (LED). Gonococcal isolates were tested for minimal inhibitory
      concentrations. BV was found in 56%, trichomoniasis in 25%, and syphilis in 6% of
      the women. LCR detected gonorrhoea in 13% and chlamydial infection in 11% of the
      women. Detection of Gram(-) intracellular diplococci in endocervical smears, and
      gonococcal culture were respectively 23% and 57% sensitive and 98% and 100%
      specific compared to LCR. Chlamydia antigen detection by IF was 75% sensitive and
      77% specific compared to LCR. Leucocytes in endocervical smears and LED testing
      lacked precision to detect gonococcal and chlamydial infections. Of 67 gonococcal
      strains evaluated, 19% were fully susceptible to penicillin, 33% to tetracycline;
      all were susceptible to ciprofloxacin, ceftriaxone, and spectinomycin. Patients
      who present with genital discharge in Madagascar should be treated syndromically
      for gonococcal and chlamydial infections and screened for syphilis. Gonorrhoea
      should be treated with ciprofloxacin.

PMID- 12230925
TI  - Sexually transmitted diseases and sexual lifestyles of long-distance truck
      drivers: a clinico-epidemiologic study in south India.
AB  - Our study objective was to determine the prevalence and pattern of sexually
      transmitted diseases (STDs) and to study sexual lifestyles of long-distance truck
      drivers and their assistants in south India. For this, a total of 263 truck
      drivers/assistants were recruited from the highway clinic from October 1999 to
      March 2001. All of them were sexually active and heterosexual contact was the
      predominant mode (99.2%). Two-thirds of them had contact with commercial sex
      workers (CSWs) and roughly 60% admitted alcohol consumption. One hundred and two
      participants (38.7%) had various STDs. The positivity rates of HIV, VDRL and
      HBsAg were 15.9%, 13.3% and 21.2% respectively. The higher median age, education
      less than primary school level, longer duration of occupation, longer duration of
      each trip and a previous history of genital ulcer disease were significant risk
      factors for the acquisition of HIV infection.

PMID- 12230926
TI  - Syphilis among intravenous drug-using population: epidemiological situation in St
      Petersburg, Russia.
AB  - INTRODUCTION: An epidemic of syphilis and other sexually transmitted infections
      (STI) in the Russian Federation is believed to be related to the rise in
      injection drug use. A study was carried out in collaboration with a non
      governmental organization, Foundation 'Vozvrastcheniye'. METHODS: Nine hundred
      and ten injection drug users participating in the programme were tested for
      syphilis, HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV); 65
      participants who had laboratory markers for syphilis and 45 syphilis-negative
      serosurvey subjects agreed to participate in a questionnaire study. RESULTS:
      Syphilis, HIV, HBV and HCV were diagnosed in 12%, 0%, 48% and 79% of drug users,
      respectively. Prevalence of syphilis seromarkers was nine times higher in females
      than in males, and strongly associated with sex work. CONCLUSIONS: The results of
      the study indicate that resources to treat and prevent further infections
      including HIV should be prioritized toward risk reduction in drug injectors and
      sex workers in St Petersburg.

PMID- 12230927
TI  - Guided reflection: transcending a routine approach in the management of sexually
      transmissible infections.
AB  - This paper describes a distinctive approach to the sexually transmissible
      infections (STI) clinical consultation: 'the guided reflection approach'. The
      authors coined this term and identified the guided reflection approach through
      analysis of 22 in-depth interviews with practitioners who provide care for people
      with STI, and 34 people who had attended a healthcare facility in Australia for
      screening or treatment of an STI. A grounded theory method was used to collect
      and analyse this information. The data revealed when the STI consultation is
      conducted using the principles characterized by the guided reflection approach
      creates contexts for sexual empowerment that have the potential to effectively
      assist people to gain autonomy for safe sex. Routinely, most of the practitioners
      in this study were shown to direct the STI consultation towards risk behaviours
      and practices and prevention of transmission, with minimal intervention. However,
      this study shows that if clinical interaction is to make a difference to the
      patient's autonomy for sexual behaviour, two changes will be required. First,
      practitioners need to adopt the goal of assisting patients to attain levels of
      autonomy, and second, practitioners require education to assist them to develop
      the interactive skills needed to engage patients in dialogue and reflection about
      sexual behaviour.

PMID- 12230928
TI  - Drug use and HIV risk in Trinidad and Tobago: qualitative study.
AB  - Crack use is an important risk factor for HIV infection because of its
      association with unsafe sexual practices. We investigated factors promoting the
      initiation of crack cocaine use; the sexual behaviour of crack users; and their
      rehabilitation care seeking behaviour in Trinidad and Tobago. We conducted 40 in
      depth interviews with drug users. Respondents frequently reported a history of
      parental desertion, alcohol abuse, and physical abuse within the family. They
      perceived peer pressure and drug use in the family as important factors promoting
      first drug use. Exchanging sex for drugs was common, and practising oral sex was
      considered safe. Female drug users rarely seek rehabilitative care because of
      stigmatization and lack of care for their children. In Trinidad, attitudes
      towards drugs in society and families need to be changed. Campaigns promoting
      safer sex should emphasize the risk of oral sex. Rehabilitation facilities caring
      for female drug users should offer child care.

PMID- 12230929
TI  - Urology update--common conditions.

PMID- 12230930
TI  - A case of march fracture in a patient with osteoporosis on long-term HAART.

PMID- 12230931
TI  - Cost-effectiveness of imiquimod for anogenital warts.

PMID- 12230932
TI  - Frequency of p12K and p12R alleles of HTLV Type 1 in HAM/TSP patients and in
      asymptomatic HTLV type 1 carriers.
AB  - HTLV-1 has a complex genome, and contains four open reading frames (ORFs) in the
      3' region encoding viral and cellular regulatory proteins. p12 is a small, ORF I
      encoded hydrophobic protein, the function of which is not well understood. It has
      been shown that p12 enhances the E5-transforming ability of bovine
      papillomavirus; and binds to the 16-kDa subunit of the vacuolar ATPase pump,
      immature forms of the beta and gamma(c) chains of the interleukin 2 receptor, and
      the free chain of MHC I. p12 carrying a lysine residue (p12K) at position 88 of
      its sequence may be rapidly degraded in the cell via proteasome, whereas p12 with
      an arginine residue (p12R) at the same position is severalfold more stable. These
      alleles are found in proviral DNA of HTLV-1-infected individuals and it was
      previously observed that the p12K allele was more frequent in HAM/TSP (HTLV-1
      associated myelopathy/tropical spastic paraparesis) patients and was not found at
      all in asymptomatic carriers, whereas patients with adult T cell
      leukemia/lymphoma (ATLL) carry the p12R allele. To extend these observations and
      verify whether the p12K mutation could be used as a marker of progression to
      HAM/TSP, we analyzed 37 HAM/TSP patients and 40 asymptomatic carriers at
      different stages of infection. In our cohort, only one HAM/TSP patient carried
      the p12K phenotype, which accounted for a frequency of 2.7% (1 of 37). We also
      found, among the 40 asymptomatic HTLV-1 carriers, one who presented the p12K
      phenotype, contrasting with previous publications. Thus, p12K does not seem to be
      universally diagnostic for HTLV-1-associated neurological disease. Further
      screening of HTLV-1-infected individuals in other populations may elucidate this
      observation.

PMID- 12230933
TI  - Response and relapse rates of candidal esophagitis in HIV-infected patients
      treated with caspofungin.
AB  - Caspofungin is a new antifungal drug of the echinocandin class. We analyzed the
      clinical efficacy of caspofungin (50 mg/day) in the treatment of HIV-infected
      adults with endoscopically documented Candida esophagitis and enrolled in four
      clinical trials of caspofungin. Symptoms were evaluated daily; a favorable
      outcome required complete resolution of all esophageal symptoms assessed at the
      time of discontinuation of therapy. Relapse was defined as recurrent symptoms
      during the subsequent 2 weeks. A multivariate logistic regression model was
      developed to identify potential factors (including severity of symptoms at
      presentation, CD4(+) cell count on entry, extent of disease [assessed
      endoscopically at baseline], causative Candida species, duration of therapy
      [overall and after resolution of symptoms], time on treatment before symptom
      resolution, and antifungal prophylaxis) that might predict symptomatic relapse in
      the 2 weeks following completion of therapy. The median CD4(+) lymphocyte count
      for the entire population was 31/mm(3). Candida albicans was isolated from 109 of
      110 patient samples cultured for the pathogen and constituted the sole isolate in
      77%. Extensive esophageal involvement was present in 55% of patients at the time
      of pretreatment endoscopy. The duration of therapy ranged from 7 to 20 days
      (median, 12 days). Symptoms resolved in 117 of 123 patients (95%; 95% confidence
      interval, 90-98%) with a median time of ~4 days. Response rates were 43 of 46
      (93%) and 70 of 73 (96%) for patients with greater or fewer than 50 CD4(+)
      cells/mm(3), and 80 of 85 (94%) and 23 of 24 (96%) in infections caused by C.
      albicans alone or in association with non-albicans isolates, respectively.
      Symptoms recurred within 2 weeks of stopping caspofungin in 19 of 115 evaluable
      patients (17%), including 3 of 16 (19%) receiving antifungal prophylaxis. Relapse
      rates were similar for patients with greater or fewer than 50 CD4(+) cells/mm(3).
      In this relatively small number of patients, only symptom severity and extent of
      disease judged endoscopically at baseline were significantly (p < 0.10)
      associated with early relapse in the multivariate model.

PMID- 12230934
TI  - Immunologic and virologic consequences of temporary antiretroviral treatment
      interruption in clinical practice.
AB  - To determine the long-term immunologic and virologic effects of antiretroviral
      treatment interruptions, a retrospective analysis of an ongoing observational
      database was performed at a university HIV clinic. All patients who began highly
      active antiretroviral therapy (HAART) after January 1, 1996 and (1) were HAART
      experienced for >/=90 days, (2) had a treatment interruption (TI) for >/=30 days,
      (3) resumed HAART for >/=30 days, and (4) had CD4(+) cell counts performed pre-
      and post-TI were included. Main outcome measures included the following:
      Immunologic success was defined as a post-TI CD4(+) cell count >90% of the pre-TI
      CD4(+) cell count (post-TI/pre-TI, >90%). Virologic success was defined as a post
      TI viral load (VL) less or equal to twice the pre-TI VL (post-TI/pre-TI, </=2) or
      a post-TI VL of <1000 copies/ml. The pre-TI (baseline) value was the value at the
      start of the TI (range, -20 to +7 days); the post-TI value was the highest CD4(+)
      cell count and lowest VL copy achieved during the follow-up window (270 days).
      One thousand and eight patients were included in the analysis and 75 met the
      inclusion criteria. Forty-four of 75 patients (58.6%) achieved a successful
      immunologic outcome and 52 of 68 patients (76.5%; 7 patients did not have a VL
      determined within the specified periods) achieved a successful virologic outcome.
      No factors predicting success were identified. The median CD4(+) cell counts pre-
      and post-TI were 233 and 231 cells/microl, respectively; the median VLs pre- and
      post-TI were 11,456 and 404 copies/ml, respectively. We conclude that the
      majority of our patients in virologic failure who underwent a temporary TI
      recovered 90% of their baseline CD4(+) cell counts and returned to within 2-fold
      of their baseline VL when HAART was resumed.

PMID- 12230935
TI  - Suppression of clonogenic potential of human bone marrow mesenchymal stem cells
      by HIV type 1: putative role of HIV type 1 tat protein and inflammatory
      cytokines.
AB  - Bone marrow abnormalities are frequently observed in HIV-1-infected individuals.
      Infection of marrow mesenchymal stem cells (MSCs) may abrogate their growth
      properties and hematopoietic supportive functions. To delineate the cell type
      infected, and factors responsible for the deleterious effects, human bone marrow
      cells were exposed to HIV-1 in vitro. By week 4, the ability of MSCs to form
      colonies of purely fibroblasts (CFU-F) and mixed colonies of fibroblasts and
      adipocytes (CFU-FA) was suppressed by 23 +/- 5 and 55 +/- 7%, respectively. The
      p24 concentration in culture supernatants steadily declined from 170 ng/ml in the
      inoculum to 134 +/- 30, 35 +/- 15, 2.3 +/- 3, and <0.02 ng/ml at the end of week
      1, 2, 3, and 4, respectively. However, even at week 4, coculturing with MT-4
      lymphocytes for 1 week dramatically increased p24 levels. Polymerase chain
      reaction (PCR) amplification, using HIV-1-specific primers, and in situ
      hybridization with an HIV-1 cDNA probe demonstrated the presence of virus
      specific nucleic acids within stromal colonies. Coimmunostaining with antibody to
      CD83 implicated the presence of HIV-1 within dendritic progenitor cells.
      Immunostaining with HIV-1 Tat antibody demonstrated the presence of Tat protein
      and reverse transcriptase (RT)-PCR assays showed increased (160-220%) mRNA levels
      for inflammatory cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin
      1beta [IL-1beta], IL-6, and macrophage inflammatory protein 1alpha [MIP-1alpha]).
      A concentration-dependent decrease in CFU-STROs was observed on incubation with
      either Tat protein (1-100 ng/ml) or with TNF-alpha or IL-1beta (0.025-25 ng/ml).
      These results suggest that HIV-1 infection of stromal cells may produce
      inhibitory factors that suppress the clonogenic potential of MSCs.

PMID- 12230936
TI  - Herpesvirus saimiri-immortalized human lymphocytes: novel hosts for analyzing HIV
      type 1 in vitro neutralization.
AB  - Herpesvirus saimiri-immortalized CD4(+) T lymphocytes (HVS T cells) are activated
      memory cells that support efficient replication of primary R5 strains of HIV-1,
      which predominate in virus transmission. Being continuous, they are
      phenotypically more stable and technically less demanding than peripheral blood
      mononuclear cells (PBMCs). Here we present the first report using HVS T cells to
      assay HIV-1 neutralization in vitro. Neutralization sensitivities of paired
      viruses isolated from individuals in both HVS T cells (CN-2 cells) and PBMCs were
      similar, with homologous and heterologous plasma/sera in both CN-2- and PBMC
      based assays. Analysis of V3 loop and CD4-binding site (CD4-BS) sequences showed
      that changes present in CN-2 isolates were neither more numerous nor more
      significant than those selected in their PBMC counterparts. Neutralization
      profiles of CN-2/PBMC virus pairs were similar again when V3- and CD4-binding
      site (BS)-specific monoclonal antibodies, whose mapped epitopes were conserved or
      of similar sequence in the virus pairs, were tested. Unlike other T cell line
      isolates, CN-2 isolates were not more sensitive to neutralization than their PBMC
      counterparts. We also show that HVS T cells do not appear to exert significant
      biological selection pressures on primary isolates. Paired viruses have a similar
      phenotype with respect to syncytium formation, cell tropism, and coreceptor
      usage. Thus CN-2 cells are suitable hosts for assaying neutralization and could
      be useful in standardizing neutralization assays performed in different
      laboratories.

PMID- 12230937
TI  - Common genetic arrangements among human immunodeficiency virus type 1 subtype A
      and D recombinant genomes vertically transmitted in Tanzania.
AB  - Human immunodeficiency virus type 1 (HIV-1) subtypes A, C, and D are
      cocirculating in Tanzania, and large numbers of recombinant genomes have been
      reported from this region. Here we describe full-length sequences of six unlinked
      HIV-1 subtype A and D recombinants. The samples came from newborns, indicating
      that the recombination patterns were vertically transmitted and were functionally
      competent. All six genomes had different recombination patterns with one to eight
      cross-over points frequently located at the beginning or end of functionally
      defined regions. In five of the six viruses most of gag, pol, tat, and rev and
      the intracytoplasmic domain of gp41 were classified as subtype D. In all but one
      genome, the external domain of gp41 and the majority of gp120 belonged to subtype
      A. A recombination site common to four of the six genomes was located at the
      transmembrane domain of gp41, at the end of the rev response element. The
      identification of subtype patterns among intersubtype recombinant genomes from
      recently infected individuals may reveal genetic determinants of improved viral
      fitness or advantage for transmission.

PMID- 12230938
TI  - A new cell line-based neutralization assay for primary HIV type 1 isolates.
AB  - Simple and standardized assays for detection and quantification of neutralizing
      antibodies to primary HIV-1 isolates are needed in research on HIV-1 vaccines and
      pathogenesis. Here we describe a new HIV-1 neutralization assay that is based on
      plaque formation in U87.CD4-CCR5 and U87.CD4-CXCR4 cells, which is an attractive
      alternative to peripheral blood mononuclear cell-based assays. Infected cells
      form syncytia, that is, plaques, that can be stained with hematoxylin and
      enumerated by light microscopy. Neutralization is determined by the ability of a
      serum to reduce the number of plaque-forming units (PFU) relative to controls
      exposed to medium or negative serum. The intraassay variation of the plaque
      forming unit determinations was tested with 15 serum-virus combinations and
      showed good reproducibility. The differences ranged from -19 to +27% and had a
      standard deviation of +/- 9.1%. On the basis of these data the cutoff for
      neutralization (i.e., plaque reduction) was set to 30% (3.3 standard deviations).
      Virus titration experiments showed that neutralization results were dependent on
      virus dose and therefore the neutralization assays should be performed with a
      virus dose of 10-100 PFU/well. The reproducibility of the new neutralization
      assay was tested with 4 primary viruses and 9 sera for a total of 20 virus-serum
      combinations. The mean difference in neutralization (i.e. plaque reduction)
      determinations performed on different days was as small as 11%. None of 10
      Swedish sera and 1 Ugandan plasma pool from HIV-1-uninfected subjects were
      positive for neutralization, indicating that the assay has high specificity. In
      summary, the new U87.CD4 cell line-based neutralization assay for primary HIV-1
      isolates is a highly reproducible, sensitive, and high-throughput assay that is
      well suited for large-scale HIV-1 neutralization studies.

PMID- 12230939
TI  - Increasing CD4+ T cells specific for tuberculosis correlate with improved
      clinical immunity after highly active antiretroviral therapy.
AB  - Treatment advances have led to dramatic clinical improvements for patients with
      HIV-1 infection. These clinical improvements reflect treatment-related
      improvements in immune function, which are most striking in individuals who
      develop exaggerated immune inflammatory responses to occult opportunistic
      infections. The mechanisms accounting for these exaggerated immune responses are
      unknown. To gain insight into these mechanisms, we intensively studied a subject
      untreated for disseminated tuberculosis and HIV-1 coinfection who then began
      treatment for both diseases. We examined the changing frequencies of
      Mycobacterium tuberculosis (MTB)-specific CD4(+) T cells that produced interferon
      gamma (IFN-gamma) after short-term stimulation with MTB antigen, and we compared
      these frequencies with those in HIV-1-seronegative subjects with and without
      prior exposure to MTB antigens. For the HIV-1/MTB-coinfected subject, the
      proportion of peripheral blood CD4(+) T cells expressing MTB-specific IFN-gamma
      was 8.6% at 11 days, 11% at 33 days, and 33% at 95 days after starting treatment
      for HIV-1. CD4(+) IFN-gamma(+) T cells had a CD45RA(-)CD62L(-) (effector memory)
      phenotype and most coexpressed interleukin 2. Median frequencies of CD4(+) IFN
      gamma(+) T cells from six subjects without and nine subjects with prior exposure
      to MTB antigens were 0.06 and 0.46%, respectively. We conclude that individuals
      starting treatment for disseminated tuberculosis and HIV-1 coinfection can
      accumulate remarkably large numbers of MTB-specific CD4(+) T cells in the
      peripheral blood. The rapid expansion of antigen-specific effector CD4(+) T cells
      is one mechanism to explain immediate improvements in clinical immunity after HIV
      1 treatment. This mechanism provides a theoretical framework to understand the
      unusual inflammatory responses recently reported to occur after starting HIV-1
      treatment.

PMID- 12230940
TI  - Gene for chinese rhesus macaque DC-SIGN predicts the existence of A but not B
      isoforms of the protein.
AB  - We report here the gene for DC-SIGN from Chinese rhesus macaques. DC-SIGN is a C
      type lectin expressed by dendritic cells (DCs). It is involved in the interaction
      of DCs with T cells, and in transmission to T cells of HIV-1 and SIV. Alternative
      splicing in human DC-SIGN yields A and B isoforms of the protein. The overall
      organization of the rhesus macaque gene is similar to that of the human gene.
      Translation of B isoforms cannot occur because of a point substitution. The
      coding sequence shows that we have cloned a fourth allele for rhesus macaque DC
      SIGN. This allele shows high homology to the other rhesus macaque alleles.
      However, at the protein level, the homology is highest with the pigtail macaque
      protein. This suggests a convergent evolution of DC-SIGN in macaques living in
      China. The importance of DC-SIGN variability in the immune response remains to be
      investigated.

PMID- 12230941
TI  - Characterization of nef gene of HIV type 1 in highly active antiretroviral
      therapy treated AIDS patients with discordance between viral load and CD4+ T cell
      counts.
AB  - The advent of highly active antiretroviral therapy (HAART) has been effective in
      the treatment of AIDS patients. However, after receiving this treatment for
      various periods of time, there is in some patients a significant increase in
      plasma viral load without a decrease in CD4+ T cell count. Our study involved
      nine such AIDS patients showing this discordance. We characterized changes in the
      nef gene of plasma HIV-1 isolated from these patients. Viral RNA was extracted
      from patient plasma, amplified by RT-PCR, cloned, and sequenced. Three sequences
      from each patient were obtained. The sequences were aligned and compared with
      other strains of HIV-1. Various substitutions were seen in most patients;
      however, two patients showed unique insertions of different sizes that are
      probably due to HAART.

PMID- 12230942
TI  - Effects of dl-praeruptorin A on interleukin-6 level and Fas, bax, bcl-2 protein
      expression in ischemia-reperfusion myocardium.
AB  - AIM: To investigate the effects of dl-praeruptorin (Pd-Ia) on interleukin-6 (IL
      6) level and apoptosis-related protein expression in ischemia-reperfusion
      myocardium. METHODS: Left anterior descending coronary artery was subjected to 30
      min ischemia followed by 120 min reperfusion in open-chest anesthetized rats.
      Serum IL-6 level was measured by radioimmunoassay. Apoptosis-related protein Fas,
      bax, and bcl-2 expression was detected by immunohistochemistry and computer image
      analysis system. Infiltration of neutrophils was observed using Hematoxylin-Eosin
      staining under optical microscope. RESULTS: Pd-Ia 2.0 mg/kg iv lowered serum IL-6
      level and Fas, bax, bcl-2 expression under conditions with hypotension and
      without changes on heart rate, but increased the ratio of bcl-2/bax. There
      existed a close linearity and positive correlation between IL-6 level and Fas,
      bax, bcl-2 expression. Whereas, the infiltration of neutrophils was mild.
      CONCLUSION: Pd-Ia elicits a novel target in the therapeutic prevention of
      postischemic cardiomyocyte death. The reason might be associated with modulating
      the expression of some immediate-early genes including IL-6, Fas, bax, and bcl-2
      in ischemia-reperfusion myocardium.

PMID- 12230943
TI  - Triptolide inhibits proinflammatory factor-induced over-expression of class II
      MHC and B7 molecules in renal tubular epithelial cells.
AB  - AIM: To investigate the effects of triptolide on proinflammatory factor-induced
      over-expression of class II major histocompatibility complex (class II MHC), B7
      1, B7-2, and intercellular adhesion molecule-1 (ICAM-1) in human proximal tubular
      epithelial (HKC) cells. METHODS: HKC cells were exposed to both interferon gamma
      (IFN-gamma, 200 microg/L) and tumor necrosis factor alpha (TNF-alpha, 20
      microg/L) and cultured in media containing different concentrations of triptolide
      for 24 h. Class II MHC, B7-1, B7-2, and ICAM-1 levels in HKC cells were evaluated
      by flow cytometry. ICAM-1 mRNA level was measured by semi-quantitative RT-PCR
      method. RESULTS: HKC cells expressed quite high level of ICAM-1 and very low
      levels of class II MHC, B7-1, and B7-2 molecules. Class II MHC, B7-1, B7-2, and
      ICAM-1 levels in HKC cells were significantly increased by the costimulation of
      IFN-gamma and TNF-alpha. Triptolide inhibited the over-expression of class II
      MHC, B7-1, and B7-2 molecules in a concentration-dependent manner. The up
      regulations of ICAM-1 molecules and ICAM-1 mRNA level were not altered by
      triptolide. CONCLUSION: Triptolide can significantly inhibit proinflammatory
      factors induced over-expression of class II MHC, B7-1, and B7-2 costimulatory
      factors in tubular epithelial cells. These results may contribute to the
      therapeutic effects of triptolide in some renal diseases.

PMID- 12230944
TI  - Cloning and high level nonfusion expression of recombinant human basic fibroblast
      growth factor in Escherichia coli.
AB  - AIM: To obtain high-level expression of nonfusion recombinant human basic
      fibroblast growth factor (rhbFGF). METHODS: hbFGF cDNA was prepared from the
      total RNA of embryonic brain tissue. As a template, the obtained gene was used to
      clone nonfusion rhbFGF. New primers were employed to alter the translation
      initiation region (TIR) and reduce the G+C content through nucleotide change.
      Using pET-3C as vector, the cloned rhbFGF was expressed in BL21 (DE3). RESULTS:
      rhbFGF was expressed in E coli up to 30 % of the total cellular protein. Cation
      exchange and heparin affinity chromatography were employed to purify the target
      protein from the supernatant of bacteria lysate. The bioactivity of the purified
      rhbFGF was identical with the standard bFGF. CONCLUSION: Modification of TIR is
      an effective means to increase nonfusion expression rate of recombinant proteins,
      such as rhbFGF, in E coli.

PMID- 12230945
TI  - Protective effects of Ganoderma lucidum polysaccharides peptide on injury of
      macrophages induced by reactive oxygen species.
AB  - AIM: To study the protective effects of Ganoderma lucidum polysaccharides peptide
      (GLPP) on the mice peritoneal macrophages injured by reactive oxygen species
      (ROS), derived from tert-butylhydroperoxide (tBOOH) in vitro and in vivo.
      METHODS: Mice peritoneal macrophages were injured by ROS, derived from tBOOH. The
      survival rate of macrophages was measured by MTT assay, and the morphological
      changes of macrophages were observed under light and electron microscopes.
      RESULTS: GLPP (50, 100, 200 mg/kg, ip for 5 d) could inhibit the foam cell
      formation and necrosis of macrophages. The survival rate of macrophages was
      increased. GLPP (3.125, 12.5, 50, 200 mg/L) given to the cultured macrophages
      brought the same protective effects. Under the electron microscope it was found
      that GLPP (100 mg/kg, ip, for 5 d) could protect the organelle such as
      mitochondria against injury by tBOOH. CONCLUSION: GLPP had significant scavenging
      ROS and antioxidant effects.

PMID- 12230946
TI  - In vitro permeation of tetramethylpyrazine across porcine buccal mucosa.
AB  - AIM: To examine the in-vitro transport route of tetramethylpyrazine (TMP) across
      porcine buccal mucosa and to investigate the effects of drug concentration, pH in
      donor chamber, and 1-octanol/buffer partition coefficient on transbuccal
      permeation. METHODS: In-vitro permeation of TMP through porcine buccal mucosa was
      studied by using in-line flow through diffusion cells at 37 . The permeability of
      TMP was evaluated at different donor pH and drug concentration. Permeability of
      unionized (Pu) and ionized TMP (Pi) was calculated by using the Scientist
      software. RESULTS: The steady state flux of TMP increased linearly with the donor
      concentration (r2=0.96) at pH 7.4. The permeability and the partition coefficient
      increased with pH. Pu and Pi were 9.05 x 10(-6) cm.s(-1) and 2.99 x 10(-7) cm.s(
      1), respectively. The total permeability coefficient increased with the fraction
      of unionized form. CONCLUSION: TMP permeated through buccal mucosa by a passive
      diffusion process. The partition coefficient and pH dependency of drug
      permeability indicated that the drug was transported mainly via the transcellular
      route by a partition mechanism.

PMID- 12230947
TI  - E-4031 enhanced Ca2+ transient and ventricular myocytes contraction via reverse
      mode Na+/Ca2+ exchange in normal and hypertrophic rats.
AB  - AIM: To study the effects of N-[4-[[1-[2-(6-methyl-2-pyridinyl)ethyl]-4
      piperidinyl]carbonyl]phenyl]methanesulfonamide dihydrochloride dihydrate (E
      4031), a specific Ik blocker, on Ca2+ transient and cell contraction of normal
      and hypertrophied rat ventricular myocytes. METHODS: Electrically triggered Ca2+
      transient and cell shortening were measured simultaneously using the Ion Imaging
      System with charge coupled digital (CCD) camera. RESULTS: E-4031 (10 micromol/L)
      increased Ca2+ transient and cell shortening from (210+/-49) and (3.0+/-0.8)
      micron to (245+/-47) and (3.6+/-1.0) micron, respectively (P<0.05) in normal
      cardiomyocytes and from (196+/-54) and (3.0+/-1.3) micron to (240+/-49) and
      (3.6+/-1.3) micron respectively (P<0.05) in hypertrophied cardiomyocytes, while
      did not change calcium sensitivity in both groups. KB-R7943 completely blocked
      the activating effects induced by E-4031 in both of normal and hypertrophied
      cardiomyocytes. Nicardipine did not block the increasing effects of E-4031.
      CONCLUSION: E-4031 increased Ca2+ transient and cell contraction via stimulating
      reverse mode of Na+/Ca2+ exchange while without influencing calcium sensitivity.
      These effects were more notable in hypertrophied cardiomyocytes than in normal
      myocytes.

PMID- 12230948
TI  - Caspase 3 gene expression and [Ca2+]i homeostasis underlying desipramine-induced
      C6 glioma cell apoptosis.
AB  - AIM: To study desipramine (Des)-induced apoptosis and regulation of caspase 3
      gene expression and [Ca2+]i homeostasis in rat glioma C6 cells. METHODS:
      Apoptotic DNA breaks were quantified by propidium iodide (PI) incorporation using
      flow cytometry (FCM) and were detected by DNA agarose gel electrophoresis.
      Expression of apoptotic effector gene caspase 3 was assessed by reverse
      transcription polymerase chain reaction (RT-PCR). Single cell [Ca2+]i was
      measured using fluorescence indicator Fura-3/AM with confocal laser scanning
      microscopy. RESULTS: Des induced apoptotic DNA breaks in a concentration
      dependent manner evidenced by hypodiploid peak on FCM histogram and the apoptotic
      cell percentage induced by Des 10, 20, and 40 micromol/L for 24 h was 5.2 %, 21.9
      %, and 41.9 %, respectively. Apoptotic DNA breaks were further confirmed by a
      typical "DNA ladder" on agarose gel electrophoresis after exposure to Des 40
      micromol/L for 24 h. Meanwhile, expression of caspase 3 gene was observed
      following Des 20 micromol/L treatment. Des 40 micromol/L resulted in an early
      sustained increase in [Ca2+]i over 28 min and the elevation magnitude was greatly
      decreased by removal of extracellular free [Ca2+]i with calcium-chelator egtazic
      acid, suggesting that Des elicited [Ca2+]i influx rather than intracellular
      calcium mobilization. CONCLUSION: Up-regulation of caspase 3 gene expression and
      disturbance of homeostasis in calcium signaling system might play pivotal roles
      in Des-induced apoptotic DNA breaks of C6 cells.

PMID- 12230949
TI  - Apoptosis of rat osteoblasts in process of calcification in vitro.
AB  - AIM: To establish a cell model of osteoblasts retaining their differentiated
      phenotype in culture and observe the apoptosis of osteoblasts in the process of
      calcification using a novel acetylcholinesterase (AChE) staining method. METHODS:
      Osteoblasts were isolated enzymatically from skull of newborn SD rats; alkaline
      phosphatase (AKP) activity was determined by reformed cobalt method and azo dye
      method; mineral deposition was assessed with Von Kossa staining and Fluo-3
      staining; a novel AChE staining method was used to assay cellular apoptosis based
      on the higher expression of AChE in apoptotic cells. RESULTS: During the 44 d of
      cells cultured, primary rat skull-derived osteoblasts progressively developed
      into a bone-like tissue of multi-layered nodules of cells with mineralized extra
      cellular matrix and the apoptotic cells increased while the matrix calcificated.
      CONCLUSION: The phenotype of developmental sequence of rat skull-derived
      osteoblasts can reflect the maturation of osteoblasts in vitro. It is a
      convenient model for the research of osteoblasts biology.

PMID- 12230950
TI  - Protective effect of polypeptide from Chlamys farreri on hairless mice damaged by
      ultraviolet A.
AB  - AIM: To study the protective effect of the polypeptide isolated from Chlamys
      farreri (PCF) on hairless mice skin damaged by ultraviolet A. METHODS: Enzymes
      and malondialdehyde (MDA) were determined by biochemical methods; the expressions
      of Bcl-2 protein and NOS protein were examined by immunohistochemical technique.
      The ultra-structure of the skin was observed through electronic microscope.
      RESULTS: PCF could enhance the activities of glutathione peroxidase (GSH-px),
      superoxide dismutase (SOD), and total anti-oxidative capacity (T-AOC). Also PCF
      could reduce the amount of MDA, increase the expression of Bcl-2 protein, and
      inhibit the expression of NOS protein. The ultra-structure of epidermis and
      fibroblasts remained normal in 20 % PCF groups; there were vacuoles in smooth
      endoplasm reticulum in epidermis of mice and the number of rough endoplasm
      reticulum in fibroblasts was decreased in model group. CONCLUSION: PCF had the
      protective effects on hairless mice skin damaged by ultraviolet A via its anti
      oxidative mechanisms.

PMID- 12230951
TI  - Effects of glucocorticoid on proliferation, differentiation, and glucocorticoid
      receptor expression in human ovarian carcinoma cell line 3AO.
AB  - AIM: To study the effects of dexamethasone (Dex), a synthetic glucocorticoid, on
      proliferation, differentiation, glucocorticoid receptor expression and regulation
      in human ovarian cancer cell line 3AO. METHODS: 3AO cells proliferation was
      evaluated by viable cell count, activity of alkaline phosphatase (AKP) and tumor
      marker CA125 level were determined; the expression and regulation of
      glucocorticoid receptor (GR) in 3AO cells was studied with radioligand binding
      assay. RESULTS: Dex inhibited the proliferation of 3AO cells accompanied by
      morphological changes in concentration- and time- dependent manner. AKP activity
      was increased and tumor marker CA125 was decreased in 3AO cells after treatment
      with Dex. The induction of AKP activity by dexamethasone was blocked by RU486, a
      potent glucocorticoid antagonist. There existed high affinity and low capacity of
      GR in 3AO cells, and the GR binding activity could be downregulated by Dex.
      CONCLUSION: Glucocorticoids play an important role in the regulation of 3AO cell
      proliferation and differentiation. There existed functional GR in 3AO cells and
      the cellular effects of dexamethasone on 3AO cells were mediated by GR.

PMID- 12230952
TI  - Protective effects of nitric oxide on hepatic steatosis induced by total
      parenteral nutrition in rats.
AB  - AIM: To investigate the effects of nitric oxide (NO) on hepatic steatosis induced
      by total parenteral nutrition (TPN) in rats. METHODS: Thirty normal Wistar rats
      were randomly divided into five groups: group A, free access to food and water;
      group B, TPN; group C, TPN plus arginine; group D, TPN plus NG-nitro-L-arginine
      methyl ester (L-NAME, NO synthase inhibitor); group E, TPN plus arginine and L
      NAME. At the seventh day, liver function tests were examined, lipid content,
      nitric oxide level, and nitric oxide synthase (NOS) activity were measured, and
      histology was examined. RESULTS: The hepatic lipid content [triglyceride (mmol/g
      tissue), cholesterol (mmol/g tissue)] in group B was increased compared with
      group A (39.3+/-2.4 and 13.1+/-1.1 vs 6.9+/-0.8 and 5.6+/-0.6) (P<0.05). It was
      higher in group D (50+/-6 and 14.1+/-1.7) than in group B (P<0.05), whereas lower
      in group C (18+/-4 and 7+/-3) than in group B (P<0.05). The activity and
      distribution of NOS in the liver were associated with the content and
      distribution of hepatic lipid. CONCLUSION: These results suggest that nitric
      oxide produced by the liver may protect hepatic steatosis induced by total
      parenteral nutrition in rats.

PMID- 12230953
TI  - Protective effect of ginsenoside Rg1 against MPTP-induced apoptosis in mouse
      substantia nigra neurons.
AB  - AIM: To explore the possible mechanism of the ginsenoside Rg1 in protecting
      substantia nigra neurons from 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine
      (MPTP)-induced apoptosis in C57BL mice. METHODS: C57BL male mice were given with
      MPTP to prepare Parkinson's disease mouse model. Different doses of Rg1 (2.5,
      5.0, and 10.0 mg/kg, respectively) were given 3 d prior to MPTP in the
      pretreatment groups. Nissl staining, TH immunostaining, and TUNEL labeling were
      used to observe the damage and apoptosis of nigral neurons. The
      immunohistochemistry assay was used to detect the protein levels of Bcl-2, Bcl
      xl, Bax, inducible nitric oxide synthase (iNOS), neuronal NOS (nNOS), and cleaved
      caspase-3. RESULTS: Compared with MPTP model group, pretreatment with Rg1 (5.0
      and 10.0 mg/kg) was shown to increase the Nissl staining neurons and TH-positive
      neurons (P<0.01), and to decrease the TUNEL-positive neurons in the substantia
      nigra zona compacta (P<0.01). Moreover, Rg1 elevated the levels of cleaved
      caspase-3, Bax, and iNOS, but reduced the levels of Bcl-2 and Bcl-xl (P<0.01).
      CONCLUSION: Rg1 has protective effect against MPTP-induced apoptosis and this
      effect may be attributed to enhancing Bcl-2 and Bcl-xl expression, reducing Bax
      and iNOS expression, and inhibiting activation of caspase-3.

PMID- 12230954
TI  - Effects of retinoic acid on metastasis and its related proteins in gastric cancer
      cells in vivo and in vitro.
AB  - AIM: To investigate the effects of all-trans retinoic acid (ATRA) on metastasis
      and its related proteins in human gastric cancer cells in vivo and in vitro.
      METHODS: Gastric cancer cells, MGC80-3 and SGC-7901, were inoculated into spleen
      subcapsule of nude mice, respectively. Nude mice were administered with ATRA (0.7
      mg/kg, ig) every other day. Six weeks later, nude mice were sacrificed. All the
      tumors formed in spleen and in liver were removed. Some of them were fixed, and
      then embedded. Others were kept in liquid nitrogen for further use. Expression
      level of proteins in tumor and in cell was analyzed by Western blot. Microvessel
      in tumor section was shown by immunohistochemistry and adhesive ability of cell
      to amnion was measured by adhesion assay. RESULTS: When inoculated nude mice were
      treated with ATRA, the xenograft tumors in spleen and metastatic tumors in liver
      were suppressed by 50 % respectively, and inhibition of microvessel formation in
      xenograft and metastatic tumors was also observed obviously. Although ATRA
      regulated expression of nm23 and mts1/p16 proteins at different patterns in vivo
      and in vitro, high ratio of nm23:mts1/p16 was in association with low adhesive
      activity of cells. In addition, ATRA induced ICAM-1 protein expression in vivo
      and in vitro. CONCLUSION: ATRA inhibits the growth of xenograft tumors and their
      metastasis to liver. This process may be associated with regulation of metastatic
      related proteins, including nm23, mts1/p16, and ICAM-1 in vivo and in vitro.

PMID- 12230955
TI  - Pharmacokinetics and partial thromboplastin time after intravenous recombinant
      hirudin variant-2 in rhesus monkeys.
AB  - AIM: To study the pharmacokinetics (PK) and changes of kaolin partial
      thromboplastin time (KPTT) following single or multiple (7 d) dosing of a novel
      recombinant hirudin variant-2 (rHV-2) via the route of iv bolus injection (50 %
      of the total dose) plus infusion (the remained 50 % of the dose) in rhesus
      monkeys. METHODS: A crossover design was applied to research the PK and KPTT
      profiles of rHV-2 after single (with total dose at 1, 3, and 6 mg/kg,
      respectively) and multiple dosing (3 mg/kg). An enzyme-linked immunosorbent assay
      (ELISA) method was utilized to determine the level of rHV-2 in plasma. RESULTS:
      The concentration profiles of rHV-2 during or after administration were dependent
      both on the loading dose and the infusion rate. Mean Cmax after bolus in three
      single dose groups were 2.90, 9.78, and 15.68 mg/L, respectively. Infusions at
      rate of 8.35, 25, and 50   g/kg/h in 1 h resulted in steady-state levels of 0.73
      0.86, 1.94-2.04, and 5.41-5.59 mg/L, respectively. The plasma rHV-2 levels during
      or after administration among doses were significantly different at most of the
      time points. Area under concentration-time curve (AUC) increased linearly with
      dose but systemic clearances were similar among different groups. KPTT was
      significantly prolonged (compared with baseline) at all dose levels, and trended
      to increase with dose. CONCLUSION: Both the loading dose and the infusion rate
      are very important for controlling the rHV-2 level, and the data may be helpful
      for optimizing dosage-regimen in clinical trials.

PMID- 12230956
TI  - Inhibitory effects of succinic acid on chemical kindling and amygdala electrical
      kindling in rats.
AB  - AIM: To investigate the effects and mechanism of succinic acid on
      pentylenetetrazol (PTZ) chemical kindling and amygdala electrical kindling in
      rats. METHODS: PTZ chemical kindling and amygdala electrical kindling models were
      established in rats. The effects of succinic acid on the behavior and
      afterdischarge of kindled rats were observed. The mice were pretreated with
      succinic acid, 30 min later, picrotoxin, a GABAA receptor antagonist was given by
      ip, then the effects of succinic acid on mice were observed. RESULTS: Succinic
      acid (100-400 mg/kg, ip) dose-dependently inhibited PTZ chemical and amygdala
      kindled seizure (P<0.05, P<0.01), elevated the afterdischarge threshold, and
      reduced the Racine's stage of amygdala kindling rats (P<0.05, P<0.01); succinic
      acid (200-400 mg/kg, ip) inhibited picrotoxin-convulsion in mice (P<0.05,
      P<0.01). CONCLUSION: Succinic acid inhibits PTZ chemical and amygdala electrical
      kindling in rats, and the inhibition mechanism may be related to the enhancement
      of GABAergic system action in the brain, especially through GABAA receptors.

PMID- 12230957
TI  - Effects of phytoestrogen genistein on electrophysiology of human atrial fibers.
AB  - AIM: To study the electrophysiological effects of phytoestrogen genistein (GST)
      on human atrial fibers. METHODS: Parameters of action potential (AP) in human
      atrial special fibers were recorded using standard intracellular microelectrode
      technique. RESULTS: GST (10-100 micromol/L) decreased the velocity of diastolic
      (phase 4) depolarization (VDD) and rate of pacemaker firing (RPF), besides, GST
      (100 micromol/L) shortened the duration of 90 % repolarization of action
      potential (APD90). L-type Ca2+ channel agonist Bay K8644 (0.5 micromol/L)
      antagonized the inhibitory effects of GST on human atrial fibers, while
      pretreatment of the fibers with N(G)-nitro-L-arginine methyl ester (L-NAME, 1
      mmol/L), an NO synthase inhibitor, failed to affect the electrophysiological
      effects of GST. CONCLUSION: GST exerted a negative chronotropic action and
      induced an accelerated repolarization of human atrial fibers. These effects were
      likely due to reduction in calcium influx.

PMID- 12230958
TI  - Effects of konjac extract on insulin sensitivity in high fat diet rats.
AB  - AIM: To evaluate the effects of konjac extract (KE) on insulin sensitivity in
      insulin resistance (IR) rats induced by high fat diet (HFD). METHODS: Wistar rats
      were fed on HFD for 4 weeks, then treated with KE 1.5, 3.0 g/kg/d and metformin
      (Met) 0.1 g/kg/d for 4 weeks, respectively. The effects of KE on intake of food
      and drink, body weight, and excretion were investigated. Serum insulin was
      measured by double-radioimmunoassay. Blood glucose, total cholesterol (TC),
      triglycerides (TG), and high-density lipoprotein-cholesterol (HDL-C) were
      measured by enzyme methods, respectively. Low-density lipoprotein-cholesterol
      (LDL-C) was calculated. Tissue glycogen was determined by modified anthracene
      ketone method and tissue TG by glycerin phosphor sour oxidation enzyme method.
      Insulin sensitivity was measured by modified glucose-insulin tolerance test (K
      value). RESULTS: HFD caused IR after 4 weeks (K value: 5.2+/-0.9 vs 8.3+/-0.7,
      P<0.01), the levels of blood insulin, TG, and LDL-C increased, while HDL-C,
      glycogen in liver and skeletal muscle decreased. The storage of TG in liver and
      skeletal muscle increased. After HFD rats were treated with KE 1.5 and 3.0 g/kg/d
      for 4 weeks, respectively, the fasting blood glucose (FBG) was decreased from
      6.4+/-0.4 to 6.05+/-0.26, 6.0+/-0.3 (P<0.01). Serum TC, TG, LDL-C were decreased,
      while HDL-C/TC was increased as compared with HFD rats. There was no significant
      effect on insulin level. KE 1.5, 3.0 g/kg/d, and Met 0.1 g/kg/d could improve
      insulin sensitivity (K values were 6.1+/-0.5, 5.9+/-0.6, and 6.5+/-0.8 vs 5.2+/
      0.9, P<0.05), elevate glycogen, and decrease TG in liver and skeletal muscle.
      CONCLUSION: KE could promote glycogen syntheses and adjust blood lipid metabolism
      so as to improve IR in HFD rats.

PMID- 12230959
TI  - Hypnotic activity of melatonin: involvement of semicarbazide hydrochloride,
      blocker of synthetic enzyme for GABA.
AB  - AIM: To assess the effect of semicarbazide hydrochloride (SCZ), the blocker of
      synthetic enzyme for GABA, on the hypnotic activity of melatonin. METHODS:
      Righting reflex method in mice and electroencephalography (EEG) in rats were used
      to determine effects of SCZ on sleep and hypnotic activity of melatonin. RESULTS:
      Melatonin displayed a marked hypnotic activity both in righting reflex experiment
      and EEG recording. SCZ had no influence on sleep parameters in mice and rats when
      it was used alone. However, it blocked the sleep-potentiation effect of melatonin
      in mice. SCZ also inhibited melatonin-induced increase in total sleep time, slow
      wave sleep time, and paradoxical sleep time, and prevented melatonin-induced
      decrease in awake time in rats. CONCLUSION: SCZ antagonized the hypnotic activity
      of melatonin. It is thought that the hypnotic activity of melatonin is mediated
      by GABAergic system.

PMID- 12230960
TI  - Recent developments in the application of the nonverbal learning disabilities
      model.
AB  - Since the original work of Myklebust et al., the concept of a syndrome of
      nonverbal learning disabilities (NLD) has undergone considerable development and
      expansion, most notably in the work of Rourke. These authors have proposed a
      model of white matter dysfunction, predominantly in the right cerebral
      hemisphere, which is thought to underlie the cognitive and behavioral impairments
      seen in individuals with NLD. Recent research has focused on assessing the
      applicability of Rourke's conceptualization of the NLD syndrome and the white
      matter model to various neurologic, neurodevelopmental, and genetic disorders.
      This paper highlights recent investigations of the NLD model with respect to
      velocardiofacial syndrome, Klinefelter syndrome, high functioning autism, neuro
      fibromatosis type I, and metachromatic leukodystrophy, and also provides a brief
      discussion of recent conceptualizations of the NLD model in the broader context
      of disorders of social and emotional functioning, and of other novel avenues of
      NLD research.

PMID- 12230961
TI  - The use of newer anticonvulsants in neuropsychiatric disorders.
AB  - Anticonvulsants are becoming increasingly popular for the management of
      psychiatric and neuropsychiatric syndromes. This may be related to antikindling
      properties of these agents in addition to modulation of gamma-aminobutyric acid,
      serotonin, and other neurotransmitters. Treatment selection is complicated by the
      inconsistent availability of randomized controlled data among the growing range
      of choices. Moreover, generalization of psychiatric to neuropsychiatric
      applications of anticonvulsant treatments is not universally applicable. This
      paper reviews the use of newer anticonvulsants in the management of
      neuropsychiatric disorders, particularly aggression and agitation. The largest
      body of treatment data is available for valproic acid, which appears to be
      efficacious and well-tolerated in a wide range of neuropsychiatric disorders.
      Less consistent data are available for other medications. Further prospective
      studies are warranted to examine the use of these medications in neuropsychiatric
      populations.

PMID- 12230962
TI  - Functional magnetic resonance imaging: emerging clinical applications.
AB  - Functional magnetic resonance imaging (fMRI) is a relatively new and noninvasive
      method of functional brain mapping. Functional MRI is increasingly being applied
      to the study of neuropsychiatric disorders, including schizophrenia, Alzheimer's
      disease, traumatic brain injury, and others. Particularly noteworthy are findings
      related to plasticity in the adult human brain. Despite the promise of fMRI for
      improving the conceptualization, assessment, and treatment of neuropsychiatric
      disorders, important technical and scientific issues remain. Future research will
      address integrating fMRI with other emerging neuroimaging techniques.

PMID- 12230963
TI  - Disorders of awareness in neuropsychiatric syndromes: an update.
AB  - Impaired awareness has been reported in a number of neuropsychiatric disorders.
      The purpose of this review is to provide an update on the current understanding
      of impaired awareness in neuropsychiatric syndromes, including Alzheimer's
      disease (AD), Parkinson's disease (PD), Huntington's disease (HD), traumatic
      brain injury (TBI), schizophrenia, mood disorders, and obsessive-compulsive
      disorder (OCD). Unawareness of illness or deficits can have important diagnostic,
      treatment, and functional implications, and further understanding of its clinical
      and neural correlates will be extremely helpful in mediating its impact.
      Nevertheless, the area of unawareness has received relatively little attention as
      compared with other manifestations of neuropsychiatric illness. Evidence
      supporting a role for the involvement of frontal and parietal lobes across
      disorders is presented. Although most research has used neuropsychologic measures
      to assess brain functioning, more recent, limited literature in AD and
      schizophrenia has begun to examine neural correlates of unawareness using
      structural and functional imaging.

PMID- 12230964
TI  - Traumatic brain injury in older adults.
AB  - Traumatic brain injury (TBI) is a serious health risk for older adults, and the
      consequences of TBI range from full recovery to death. For many who survive,
      there is a legacy of cognitive, physical, and emotional disability. Falls are the
      major cause of head injury in older adults. There are many risk factors including
      pre-existing brain disease, other diseases, and, sometimes, iatrogenic factors.
      Efforts directed at prevention are of great importance. Outcome studies indicate
      that outcome is generally worse for older people than for younger people with
      similar injuries, but older individuals also deserve aggressive rehabilitation
      directed at the best possible recovery. This review will discuss the symptoms and
      syndromes that commonly result from TBI with comments about treatment.

PMID- 12230965
TI  - Behavioral parasomnias.
AB  - Sleep is not a static state. During the sleep period, physiologic changes occur
      throughout the body and brain. This complex, dynamic process can, at times,
      result in episodes of unusual or undesirable behaviors. These phenomena are
      called parasomnias. The accurate diagnosis of this group of treatable disorders
      is important, because they can have a negative impact on sleep, health, and
      social function. In addition, some of the parasomnias may provide clues to the
      presence of other underlying pathologic conditions. The parasomnias may be
      categorized in more than one way, but any attempt to classify such a diverse
      collection of entities is likely to be somewhat arbitrary. This article discusses
      the parasomnias according to the classification of the International
      Classification of Sleep Disorders, with emphasis on those characterized by
      observable behavior. As the understanding of these disorders (and sleep, in
      general) continues to deepen, new entities and schemes of classification may
      emerge.

PMID- 12230966
TI  - Behavioral couples and family therapy for substance abusers.
AB  - Behavioral couples therapy (BCT) sees the substance-abusing patient with the
      spouse to arrange a daily "sobriety contract" in which the patient states his or
      her intent not to drink or use drugs, and the spouse expresses support for the
      patient's efforts to stay abstinent. For patients taking a recovery-related
      medication (eg, disulfiram, naltrexone), daily medication ingestion witnessed and
      verbally reinforced by the spouse also is part of the contract. Behavioral
      couples therapy also teaches communication and increases positive activities.
      Findings of the past few years have added considerably to the evidence base
      showing that BCT produces greater abstinence and better relationship functioning
      than typical individual-based treatment; BCT also reduces social costs and
      domestic violence. Noteworthy recent advances have extended the positive effects
      of BCT to women drug abusers, showed the indirect benefits of BCT for the
      couple's children, expanded BCT to include family members other than spouses,
      integrated BCT with pharmacotherapy, and started to address barriers to
      technology transfer.

PMID- 12230967
TI  - Anabolic steroid abuse and dependence.
AB  - Anabolic-androgenic steroids (AAS) are mainly used to treat androgen deficiency
      syndromes and, more recently, catabolic states such as AIDS-associated wasting.
      There is no evidence in the reviewed literature that AAS abuse or dependence
      develops from the therapeutic use of AAS. Conversely, 165 instances of AAS
      dependence have been reported among weightlifters and bodybuilders who, as part
      of their weight training regimens, chronically administered supraphysiologic
      doses, often including combinations of injected and oral AAS as well as other
      drugs of abuse. A new model is proposed in which both the "myoactive" and
      psychoactive effects of AAS contribute to the development of AAS dependence. The
      adverse consequences of AAS are reviewed, as well as their assessment by means of
      a history and physical, mental status examination, and laboratory testing. When
      patients with AAS use disorders are compared with patients with other substance
      use disorders, both similarities and differences become apparent and have
      implications for treatment.

PMID- 12230968
TI  - Current perspectives on smoking cessation among substance abusers.
AB  - The prevalence of nicotine dependence among alcohol or other substance abusers is
      extremely high, and surveys have revealed that many patients in drug or alcohol
      treatment programs are interested in smoking cessation. However, smoking
      cessation has not been a traditional focus in clinical interventions for this
      population. Recent evidence from clinical trials among individuals abusing
      alcohol, marijuana, cocaine, or opioids have shown the following: 1) smokers with
      a past but not current history of alcohol dependence have a similar rate of
      success compared with non-alcoholic smokers; 2) tobacco abstinence does not
      increase alcohol relapse; 3) continued smoking adversely affects treatment for
      marijuana dependence; 4) patterns of cocaine and nicotine use are interrelated;
      5) smoking cessation rates among opioid-dependent individuals are several times
      lower than in the general US population. Smoking cessation is indicated for
      substance dependent persons already in recovery and may protect against relapse
      to the illicit drug of abuse.

PMID- 12230969
TI  - Adolescent substance abuse treatment: evidence-based practice in outpatient
      services.
AB  - Adolescent substance use disorder (SUD) is a serious public health concern. The
      majority of youth with SUD receive outpatient treatment. There is a pressing need
      to improve treatment outcome due to high rates of both premature treatment
      termination and relapse during and after treatment completion. Reviews of the
      latest innovations in the treatment of adolescent substance abuse and the recent
      completion of several randomized clinical trials examining singular and
      integrative treatment modalities have established empiric support for the
      efficacy of adolescent treatment. Despite some prominent differences in treatment
      modalities, design, and methodology, recent studies have reported remarkably
      similar short-term outcomes. Taken together, the findings represent significant
      developments in treatment outcome research, and lay the foundation for continued
      future research addressing important challenges. Potential directions include
      improving short- and long-term outcomes, enhancing motivation for treatment,
      improving engagement strategies, identifying challenges associated with
      psychiatric comorbidity, addressing patient-treatment matching, and developing
      aftercare programs.

PMID- 12230970
TI  - Translating axon guidance cues.
AB  - Recent studies suggest that local translation of mRNA within axons plays a key
      role in two aspects of growth cone navigation. One line of evidence implies a
      local synthesis of proteins that mediate growth cone collapse and turning in
      response to guidance cues; another indicates that growth cones possess the
      machinery that would allow the local synthesis of receptors for axon guidance
      cues.

PMID- 12230971
TI  - Is the progress zone model a victim of progress?
AB  - The prevailing view has long been that mesenchymal cells at the apex of the
      vertebrate limb bud proliferate in a progress zone (PZ) under the influence of
      the apical ectodermal ridge (AER). According to the PZ model, proximodistal cell
      fates are specified according to the time spent in the PZ. New results,
      considered along with some earlier findings, fail to support this model.

PMID- 12230972
TI  - RNA logic in time and space.
AB  - An EMBO-sponsored workshop entitled "Translational Control in Development and
      Neurobiology" was held recently in Mallorca, Spain. The talks covered mechanisms
      of translational regulation, particularly in terms of temporal and spatial
      regulation, over a wide range of biological systems.

PMID- 12230974
TI  - Single-stranded antisense siRNAs guide target RNA cleavage in RNAi.
AB  - Small interfering RNAs (siRNAs) are the mediators of mRNA degradation in the
      process of RNA interference (RNAi). Here, we describe a human biochemical system
      that recapitulates siRNA-mediated target RNA degradation. By using affinity
      tagged siRNAs, we demonstrate that a single-stranded siRNA resides in the RNA
      induced silencing complex (RISC) together with eIF2C1 and/or eIF2C2 (human
      GERp95) Argonaute proteins. RISC is rapidly formed in HeLa cell cytoplasmic
      extract supplemented with 21 nt siRNA duplexes, but also by adding single
      stranded antisense RNAs, which range in size between 19 and 29 nucleotides.
      Single-stranded antisense siRNAs are also effectively silencing genes in HeLa
      cells, especially when 5'-phosphorylated, and expand the repertoire of RNA
      reagents suitable for gene targeting.

PMID- 12230973
TI  - An RNA thermosensor controls expression of virulence genes in Listeria
      monocytogenes.
AB  - In Listeria monocytogenes, virulence genes are maximally expressed at 37 degrees
      C, almost silent at 30 degrees C and controlled by PrfA, a transcriptional
      activator whose expression is thermoregulated. Here, we show that the
      untranslated mRNA (UTR) preceding prfA, forms a secondary structure, which masks
      the ribosome binding region. Mutations predicted to destabilize this structure
      led to virulence gene expression and invasion of mammalian cells at 30 degrees C.
      Chemical probing, native gel electrophoresis, in vitro translation, and
      "compensatory" and "increased stability" mutations demonstrated that the UTR
      switches between a structure active at high temperatures, and another inactive at
      low temperatures. Strikingly, when the DNA corresponding to the UTR was fused to
      gfp in E. coli, bacteria became fluorescent at 37 degrees C, but not at 30
      degrees C. This mechanism of posttranscriptional thermoregulation may have
      important applications.

PMID- 12230975
TI  - OcaB is required for normal transcription and V(D)J recombination of a subset of
      immunoglobulin kappa genes.
AB  - OcaB, a transcriptional coactivator also known as Bob-1 or OBF-1, was isolated on
      the basis of its ability to enhance transcription of immunoglobulin (Ig) genes in
      vitro. Paradoxically, OcaB(-/-) mice showed no apparent deficiency in Ig gene
      transcription, only cellular immune defects including absence of germinal centers
      (GC) and decreased numbers of immature B cells; the genes targeted by OcaB were
      not determined. Here we report that OcaB is essential for V(D)J recombination of
      a subset of Igkappa genes. We show that OcaB modulates recombination by directly
      enhancing Igkappa gene transcription in vivo.

PMID- 12230976
TI  - A structural mechanism of integrin alpha(IIb)beta(3) "inside-out" activation as
      regulated by its cytoplasmic face.
AB  - Activation of the ligand binding function of integrin heterodimers requires
      transmission of an "inside-out" signal from their small intracellular segments to
      their large extracellular domains. The structure of the cytoplasmic domain of a
      prototypic integrin alpha(IIb)beta(3) has been solved by NMR and reveals multiple
      hydrophobic and electrostatic contacts within the membrane-proximal helices of
      its alpha and the beta cytoplasmic tails. The interface interactions are
      disrupted by point mutations or the cytoskeletal protein talin that are known to
      activate the receptor. These results provide a structural mechanism by which a
      handshake between the alpha and the beta cytoplasmic tails restrains the integrin
      in a resting state and unclasping of this interaction triggers the inside-out
      conformational signal that leads to receptor activation.

PMID- 12230977
TI  - Global conformational rearrangements in integrin extracellular domains in outside
      in and inside-out signaling.
AB  - How ligand binding alters integrin conformation in outside-in signaling, and how
      inside-out signals alter integrin affinity for ligand, have been mysterious. We
      address this with electron microscopy, physicochemical measurements, mutational
      introduction of disulfides, and ligand binding to alphaVbeta3 and alphaIIbbeta3
      integrins. We show that a highly bent integrin conformation is physiological and
      has low affinity for biological ligands. Addition of a high affinity ligand
      mimetic peptide or Mn(2+) results in a switchblade-like opening to an extended
      structure. An outward swing of the hybrid domain at its junction with the I-like
      domain shows conformational change within the headpiece that is linked to ligand
      binding. Breakage of a C-terminal clasp between the alpha and beta subunits
      enhances Mn(2+)-induced unbending and ligand binding.

PMID- 12230978
TI  - AppA is a blue light photoreceptor that antirepresses photosynthesis gene
      expression in Rhodobacter sphaeroides.
AB  - Photosynthetic bacteria regulate photosystem synthesis in response to alterations
      in oxygen tension and light intensity. In this study we show that the PpsR
      repressor from Rhodobacter sphaeroides binds to DNA in a redox-dependent manner
      through the formation/breakage of an intramolecular disulfide bond. We also
      demonstrate that PpsR is antagonized by the flavin-containing antirepressor,
      AppA, that is capable of breaking the disulfide bond in oxidized PpsR as well as
      forming a stable AppA-PpsR(2) antirepressor-repressor complex. Blue light
      excitation of AppA induces a photocycle that is characterized by a long-lived red
      shifted absorbance of the flavin. Light-excited AppA was found to be incapable of
      forming the AppA-PpsR(2) antirepressor complex. These results establish AppA as a
      transcription factor that controls both redox and blue light repression of
      photosystem gene expression by mediating DNA binding activity of PpsR.

PMID- 12230979
TI  - An EGFR/Ebi/Sno pathway promotes delta expression by inactivating Su(H)/SMRTER
      repression during inductive notch signaling.
AB  - The Notch and Epidermal Growth Factor Receptor (EGFR) pathways both regulate
      proliferation and differentiation, and the cellular response to each is often
      influenced by the other. Here, we describe a mechanism that links them in a
      sequential fashion, in the developing compound eye of Drosophila. EGFR activation
      induces photoreceptor (R cell) differentiation and promotes their expression of
      Delta. This Notch ligand then induces neighboring cells to become nonneuronal
      cone cells. ebi and strawberry notch (sno) regulate EGFR-dependent Delta
      transcription by antagonizing a repressor function of Suppressor of Hairless
      (Su(H)). Sno binds to Su(H), and Ebi, an F-box/WD40 protein, forms a complex with
      Su(H) and the corepressor SMRTER. EGFR-activated transcriptional derepression
      requires ebi and sno, is proteasome-dependent, and correlates with the
      translocation of SMRTER to the cytoplasm.

PMID- 12230980
TI  - Disruption of DAG1 in differentiated skeletal muscle reveals a role for
      dystroglycan in muscle regeneration.
AB  - Striated muscle-specific disruption of the dystroglycan (DAG1) gene results in
      loss of the dystrophin-glycoprotein complex in differentiated muscle and a
      remarkably mild muscular dystrophy with hypertrophy and without tissue fibrosis.
      We find that satellite cells, expressing dystroglycan, support continued
      efficient regeneration of skeletal muscle along with transient expression of
      dystroglycan in regenerating muscle fibers. We demonstrate a similar phenomenon
      of reexpression of functional dystroglycan in regenerating muscle fibers in a
      mild form of human muscular dystrophy caused by disruption of posttranslational
      dystroglycan processing. Thus, maintenance of regenerative capacity by satellite
      cells expressing dystroglycan is likely responsible for mild disease progression
      in mice and possibly humans. Therefore, inadequate repair of skeletal muscle by
      satellite cells represents an important mechanism affecting the pathogenesis of
      muscular dystrophy.

PMID- 12230981
TI  - Sidekicks: synaptic adhesion molecules that promote lamina-specific connectivity
      in the retina.
AB  - A major determinant of specific connectivity in the central nervous system is
      that synapses made by distinct afferent populations are restricted to particular
      laminae in their target area. We identify Sidekick (Sdk)-1 and -2, homologous
      transmembrane immunoglobulin superfamily molecules that mediate homophilic
      adhesion in vitro and direct laminar targeting of neurites in vivo. sdk-1 and -2
      are expressed by nonoverlapping subsets of retinal neurons; each sdk is expressed
      by presynaptic (amacrine and bipolar) and postsynaptic (ganglion) cells that
      project to common inner plexiform (synaptic) sublaminae. Sdk proteins are
      concentrated at synaptic sites, and Sdk-positive synapses are restricted to the 2
      (of > or =10) sublaminae to which sdk-expressing cells project. Ectopic
      expression of Sdk in Sdk-negative cells redirects their processes to a Sdk
      positive sublamina. These results implicate Sdks as determinants of lamina
      specific synaptic connectivity.

PMID- 12230982
TI  - Coordination of copper(II) ions by the 11-20 and 11-28 fragments of human and
      mouse beta-amyloid peptide.
AB  - A potentiometric and spectroscopic (UV-vis, CD and EPR) study of Cu(II) binding
      to the (11-20), (11-28), (Ac-11-20H) and (Ac-11-28) fragments of human (H) and
      mouse (M) beta-amyloid peptide was carried out. The values of the protonation
      constants of the two lysine side chain amino groups for the (11-28) and (Ac-11
      28) fragments of beta-amyloid peptide differ noticeably suggesting considerable
      interactions between the two residues. The N-terminal amino acid sequence Xaa-Yaa
      His for the (11-20H) and (11-28H) fragments determines the coordination ability
      of the fragments studied to copper(II) ions. Addition of the (17-20) and (17-28)
      sequences to the (11-16) fragment of human and mouse beta-amyloid peptide does
      not change the coordination mode, and the stabilities of the complexes formed are
      comparable to those of the (11-16) peptide, although 1N complexes of the (11-28)
      fragments are stabilized by about one order of magnitude compared to those of the
      (11-16) peptides. The (Ac-11-28) peptides form complexes with the same
      coordination mode as those for the (Ac-11-16) fragments. The stability of the
      complexes for the (Ac-11-28H) fragment is one or two orders of magnitude higher
      compared to those of the (Ac-11-16H) fragment. This stabilization may result from
      structural organization of a peptide in copper(II) complexes.

PMID- 12230983
TI  - Interaction of mucus with freshly neutralised aluminium in freshwater.
AB  - This study examined the interaction of mollusc trail mucus, and its biochemical
      constituents, with environmentally relevant concentrations of freshly neutralised
      aluminium (Al) in freshwater. Upon neutralisation Al starts to polymerise. In the
      presence of mucus the metal is rapidly localised into the hydrated mucus gel
      resulting in a likely reduction of its overall degree of polymerisation. A simple
      Al binding assay identified large-M(r) glycoconjugates as major Al-complexing
      molecules in mucus. Subsequent isolation and purification of these mucus
      glycoconjugates showed the metal readily bound to the carbohydrate portion and,
      in particular, to acidic components such as those containing carboxyl
      functionality. It is suggested gel-forming extracellular glycoconjugates play a
      crucial role in preventing the diffusion of Al into biological systems and thus
      serve to maintain metabolic homeostasis.

PMID- 12230984
TI  - Spectroscopic and structural study of complexes of quercetin with Al(III).
AB  - Complex formation between aluminium and quercetin (Q) in methanol was studied by
      the combined use of spectroscopic measurements and quantum chemical calculations.
      Quercetin presents in its structure three possible chelating sites in
      competition. UV-visible spectroscopy has showed the successive formation of two
      complexes of stoichiometry Al(III):Q of 1:2 and 2:1, respectively. The first site
      involved in the complex formation process is the 3-hydroxychromone and the second
      one is the ortho-dihydroxyl group. Semiempirical treatment, using the AM1
      hamiltonian, permitted calculation of the structural modifications engendered by
      the ligand through chelation of one then two aluminium ions. The electronic and
      vibrational spectra have been calculated with the same method in order to compare
      them to the experimental spectra and so confirm the involved chelating sites. The
      simulated electronic spectra obtained from the complex models are in good
      agreement with the experimental UV-visible absorption spectra. In the same way
      the vibrational spectra of the complexes validate the proposed complex formation
      mechanism. The pH influence on the complexes stoichiometry and on the
      preferentially occupied chelating sites has been also investigated.

PMID- 12230985
TI  - Study of the coordination of amino acids with metals using [trans-en2Os(eta2
      H2)L]2+ as a 1H NMR probe.
AB  - This is a study of the interaction of 23 kinds of amino acids, peptides and their
      analogues with Os((II)) at different pD values. Experiments show that in acidic
      conditions, the carboxyl group in amino acids can coordinate with Os((II)), and
      there exists H-D coupling of the dihydrogen of the probe with D2O in strongly
      acidic conditions, N does not coordinate with Os((II)); In alkaline conditions,
      the carboxyl group can coordinate with Os, and the coordinating species have
      trans and cis isomers, and the trans isomer can convert to cis with time; N of 
      NH2- in alpha-amino group can coordinate with Os((II)) while that in gamma-amino
      n-butyric acid cannot do that. Since the target of some anti tumor agents are
      nucleic acids and proteins, we demonstrate a competitive mode to study how the
      anti tumor complex Me2SnCl2 binds to amino acid Ala, and the minimum binding
      amount and formation constant of the metal anti tumor metal complexes binding
      with amino acid are also obtained.

PMID- 12230986
TI  - Bactericidal activity of Ag-zeolite mediated by reactive oxygen species under
      aerated conditions.
AB  - The bactericidal activity induced by the introduction of silver ions into zeolite
      was studied. Escherichia coli was used as the test microorganism. Silver ions
      were loaded into zeolite by the ion-exchange method. Silver-loaded zeolite was
      demonstrated the strong bactericidal activity. Dissolved oxygen was an essential
      factor for the occurrence of the bactericidal activity because the activity was
      observed only under aerated condition. Superoxide anions, hydrogen peroxide,
      hydroxyl radicals and singlet oxygen were formed. Scavengers of these each
      reactive oxygen species (ROS) inhibited the bactericidal activity. This means
      that all ROS contributed to the activity.

PMID- 12230987
TI  - N-Carboxyalkyl derivatives of 3-hydroxy-4-pyridinones: synthesis, complexation
      with Fe(III), Al(III) and Ga(III) and in vivo evaluation.
AB  - A set of three N-carboxyalkyl 3-hydroxy-4-pyridinones has been studied as
      bidentate M(III) chelators (M=Fe, Al, Ga), with potential for oral
      administration. After preparation of the ligands, their protonation constants
      (log K(i)) and the stability constants of their metal complexes have been
      determined. The distribution coefficients of these compounds, between 1-octanol
      and Tris buffer pH 7.4, were measured. The effect of these compounds on the
      biodistribution of 67Ga-citrate loaded rats was investigated and compared with
      that of the administered 67Ga-complexes. Results indicated that, among these
      chelating agents, the N-carboxyethyl derivative has the highest affinity towards
      this set of metal ions, irrespective of the metal, and that it could even compete
      with transferrin, the main Fe-plasma protein. The binding affinity and the
      hydrophilic character decrease with the increase in the size of the alkylic
      chain. The biological assays indicate that the complex formation in vivo is
      characterized by a high kinetics and thermodynamic stability, suggesting a
      competition with the transferrin. All the ligands were found to enhance the
      excretion of the gallium. Noteworthy is the observed Ga bone fixation, mostly
      with the ethyl derivative, thus suggesting the potential use of the complex as a
      bone seeking agent.

PMID- 12230988
TI  - Coordination properties of adenosine-5'-monophosphate and related ligands towards
      Me2Sn(IV)2+ in aqueous solution.
AB  - The coordination of Me2Sn(IV)2+ to adenosine-5'-monophosphate (AMP) and the
      related compounds D-ribose-5-phosphate (R5P), D-glucose-1-phosphate (G1P) and D
      glucose-6-phosphate (G6P) in aqueous solution was investigated by means of
      potentiometric titration, and 1H-, 31P-NMR and Mossbauer spectroscopic methods in
      the pH range 2-11 (I=0.1 M NaClO4, 298 K). The complex of AMP and Me2Sn(IV)2+
      precipitated at low pH was characterised by elemental analysis, FT-IR and
      Mossbauer spectroscopic methods. From a comparison of the pK values obtained in
      the presence and absence of metal ion and the stability constants for the
      different systems, the coordination of [N] is excluded, while bidentate
      coordination of the phosphate group is presumed. Mossbauer spectroscopic
      measurements recorded in the glassy state confirmed bidentate coordination of the
      phosphate and the formation of mixed hydroxo complexes in the weakly acidic,
      neutral and strongly basic pH range. With increasing pH, the phosphate groups
      were replaced by the deprotonated alcoholic [O] atoms of the sugar moiety. The
      solid complex proved to be tbp structure with bidentate phosphate coordination.

PMID- 12230989
TI  - Interactions of metal ions with two quinolone antimicrobial agents (cinoxacin and
      ciprofloxacin). Spectroscopic and X-ray structural characterization.
      Antibacterial studies.
AB  - Several novel metal-quinolone compounds have been synthesized and characterized
      by analytical, spectroscopic and X-ray diffraction methods. The crystal structure
      of the four compounds, Na(2)[(Cd(Cx)3)(Cd(Cx)3(H2O))].12H2O,
      [Co(Cp)2(H2O)2].9H2O, [Zn(Cp)2(H2O)2].8H2O and [Cd(HCp)2(Cl)2].4H2O, is presented
      and discussed: HCx=1-ethyl-1,4-dihydro-4-oxo(1,3)-dioxolo(4,5-g)cinnoline-3
      carboxylic acid and HCp=1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1
      piperazinyl)-3-quinoline carboxylic acid. In all these compounds the quinolone
      acts as a bidentate chelate ligand that binds through one carboxylate oxygen atom
      and the exocyclic carbonyl oxygen atom. Complexes of ciprofloxacin were screened
      for their activity against several bacteria, showing activity similar to that of
      the ligand. In addition, the number of bacteria killed after 3 h of incubation
      with the ligand, [Co(Cp)2(H2O)2].9H2O, Ni(Cp)2.10H2O and Cu(Cp)2.6H2O, was
      determined against S. aureus ATCC25923. There is a direct relationship between
      the growth rate and the lethal rate. Against growing bacteria, the ligand is the
      most bactericidal and Cu(Cp)2.6H2O is the less bactericidal. On the contrary,
      against non-dividing bacteria, the complexes were more bactericidal than the
      ligand, with Cu(Cp)(2).6H(2)O the most bactericidal compound.

PMID- 12230990
TI  - Enzymatic degradation of 2,6-dichlorophenol by horseradish peroxidase: UV-visible
      and mass spectrometry characterization of the reaction products [corrected].
AB  - The reaction mechanism of the oxidation of 2,6-dichlorophenol (2,6-DCP) by
      horseradish peroxidase (HRP) and H2O2 has been investigated and the reaction
      products have been characterized by UV-visible and mass spectrometry. Evidence
      for the dimerization of 2,6-DCP to 3,3',5,5'-tetrachloro-4,4'-dihydroxybiphenyl
      and the subsequent fast oxidation of this product to the corresponding 3,3',5,5'
      tetrachlorodiphenoquinone have been collected. The reaction rate was found to
      decrease markedly as soon as the pH was raised, with a clear inflection point at
      pH congruent with 6.6-6.9; it also resulted independent from H2O2 concentration.
      Since the pK(a) for 2,6-DCP is 6.80, the reaction rate might be influenced by the
      protonation state of the substrate.

PMID- 12230991
TI  - Syntheses, characterization and X-ray structures of the fac-[RuCl3(NO)(dppe)] and
      the trans-[RuCl(NO)(dppe)2]2+ species.
AB  - Trans-[RuCl(NO)(dppe)2]2+ species were prepared. The complexes have been
      characterized by microanalysis, IR and 31P[1H] NMR spectroscopy and cyclic
      voltammetry. The trans-[RuCl(NO)(dppe)2](ClO4)2 complex shows a reversible one
      electron-reduction process at E(1/2) = 0.200 V and another one-electron-reduction
      irreversible process at -0.620 V, both centered at the NO+ group. The
      dissociation of the NO group from the trans-[RuCl(NO)(dppe)2]2+ after two one
      electron reductions results in the formation of the trans- and cis-[RuCl2(dppe)2]
      isomers. The product of an electrolyzed solution of the same complex at -0.300 V
      shows an EPR signal consistent with the presence of the [RuCl(NO(0))(dppe)2]+
      complex. Crystal data for trans-[RuCl(NO)(dppe)2]2+*[RuCl4(NO)(H2O)]*1/2[RuCl6]4
      *2[H2O] (I) and trans-[RuCl(NO)(dppe)(2)]2+*2[RuCl4(NO)(CH3O)]-*3[CH3OH] (II) are
      as follow: (I) Space group P-1, a=10.4040(3) A, b=12.3470(4) A, c=23.5620(8) A,
      alpha=95.885(2) degrees, beta=99.608(2) degrees, gamma=104.378(2) degrees,
      R=0.0521; (II) space group P-1, a=10.9769(2) A, b=13.2753(3) A, c=24.0287(4) A,
      alpha=99.743(1) degrees, beta=95.847(1) degrees, gamma=97.549(1) degrees;
      R=0.0496. The fac-[RuCl3(NO)(dppe)] (III) complex has been also prepared; its
      crystal data are: space group P2(1)/n (No. 14), a=11.841(2) A, b=13.775(2) A,
      c=16.295(4) A, beta=92.81(2) degrees; R1=0.0395.

PMID- 12230992
TI  - Crime scene investigations using portable, non-destructive space exploration
      technology.
AB  - The National Institute of Justice (NIJ) and the National Aeronautics and Space
      Administration's (NASAs) Goddard Space Flight Center (GSFC) have teamed up to
      explore the use of NASA developed technologies to help criminal justice agencies
      and professionals solve crimes. The objective of the program is to produce
      instruments and communication networks that have application within both NASA's
      space program and NIJ programs with state and local forensic laboratories. A
      working group of NASA scientists and law enforcement professionals has been
      established to develop and implement a feasibility demonstration program.
      Specifically, the group has focused its efforts on identifying gunpowder and
      primer residue, blood, and semen at crime scenes. Non-destructive elemental
      composition identification methods are carried out using portable X-ray
      fluorescence (XRF) systems. These systems are similar to those being developed
      for planetary exploration programs. A breadboard model of a portable XRF system
      has been constructed for these tests using room temperature silicon and cadmium
      zinc telluride (CZT) detectors. Preliminary tests have been completed with
      gunshot residue (GSR), blood-spatter and semen samples. Many of the element
      composition lines have been identified. Studies to determine the minimum
      detectable limits needed for the analyses of GSR, blood and semen in the crime
      scene environment have been initiated and preliminary results obtained.
      Furthermore, a database made up of the inorganic composition of GSR is being
      developed. Using data obtained from the open literature of the elemental
      composition of barium (Ba) and antimony (Sb) in handswipes of GSR, we believe
      that there may be a unique GSR signature based on the Sb to Ba ratio.

PMID- 12230993
TI  - A novel multiplex for simultaneous amplification of 20 Y chromosome STR markers.
AB  - A multiplex polymerase chain reaction (PCR) assay capable of simultaneously
      amplifying 20 Y chromosome short tandem repeat (STR) markers has been developed
      to aid human identity testing and male population studies. These markers include
      all of the Y STRs that make up the "extended haplotype" used in Europe (DYS19,
      DYS385, DYS389I/II, DYS390, DYS391, DYS392, DYS393, and YCAII) plus additional
      polymorphic Y STRs (DYS437, DYS438, DYS439, DYS447, DYS448, DYS388, DYS426, GATA
      A7.1, and GATA H4). Primers for the markers DYS385, DYS389, and YCAII target
      duplicated regions of the Y chromosome and thus can provide two polymorphic peaks
      for each respective primer set. This Y STR 20plex, which utilizes 34 different
      PCR primers, is the first to include a simultaneous amplification of all the
      markers within the European "minimal" and "extended" haplotypes. Relative primer
      positions are compared between the newly developed primers described here and
      previously published ones. Efforts were made to avoid X chromosome homology in
      the primer design as well as close packing of PCR product size ranges in order to
      keep all alleles less than 350 bp through careful examination of known allele
      ranges. Haplotype comparisons between the 20plex and a commercially available kit
      found excellent agreement across the 76 samples in the Y chromosome consortium
      panel.

PMID- 12230994
TI  - The propensity of individuals to deposit DNA and secondary transfer of low level
      DNA from individuals to inert surfaces.
AB  - We have shown that there is a difference between individuals in their tendency to
      deposit DNA on an item when it is touched. While a good DNA shedder may leave
      behind a full DNA profile immediately after hand washing, poor DNA shedders may
      only do so when their hands have not been washed for a period of 6h. We have also
      demonstrated that transfer of DNA from one individual (A) to another (B) and
      subsequently to an object is possible under specific laboratory conditions using
      the AMPFISTR SGM Plus multiplex at both 28 and 34 PCR cycles. This is a form of
      secondary transfer. If a 30 min or 1h delay was introduced before contact of
      individual B with the object then at 34 cycles a mixture of profiles from both
      individuals was recovered. We have also determined that the quantity and quality
      of DNA profiles recovered is dependent upon the particular individuals involved
      in the transfer process. The findings reported here are preliminary and further
      investigations are underway in order to further add to understanding of the
      issues of DNA transfer and persistence.

PMID- 12230995
TI  - Recommendations for consistent treatment of length variants in the human
      mitochondrial DNA control region.
AB  - Human mitochondrial DNA (mtDNA) analysis is a valuable forensic tool, useful in
      cases where the amount of extracted DNA is low or highly degraded. Population
      databases are used to determine the relative rarity of a particular profile
      obtained in a forensic case. Rather than full DNA sequence information, sequence
      profiles are compared to a reference sequence, and the differences from the
      reference are recorded in forensic databases. A standard method is proposed for
      characterizing length variants, and examples are described using actual human
      control region mtDNA profiles. Consistency in alignment and nomenclature avoids
      inadvertently describing two sequences as different when in fact they are the
      same.

PMID- 12230996
TI  - A report of the 2000 and 2001 paternity testing workshops of the English speaking
      working group of the international society for forensic genetics.
AB  - During the last 10 years, the English Speaking Working Group (ESWG) of the
      International Society for Forensic Genetics (ISFG) has once a year arranged a
      Paternity Testing Workshop in which blood samples as well as a questionnaire
      concerning laboratory strategies were distributed to the participating
      laboratories. In 2000 and 2001, paper challenges were included in the workshops.
      Here, we present the results of the 2000 and 2001 Paternity Testing Workshops.
      The numbers of participating laboratories were 33 (2000) and 36 (2001). A total
      of 36% (2000) and 31% (2001) of the laboratories submitted typing results of
      variable number of tandem repeats (VNTRs) investigated with restriction fragment
      length polymorphism (RFLP) and single locus probes (SLPs). A total of 91% (2000)
      and 86% (2001) submitted typing results of polymerase chain reaction (PCR) based
      systems. Typing errors occurred in 0.3% of the submitted PCR-based results in
      2000 and in 0.1% in 2001. The results of the paper challenges showed a high
      degree of variation in the formulas used for calculation of the weight of
      evidence of rare events such as inconsistencies or possible silent alleles. The
      majority of the laboratories used the same formulas for calculations of
      frequently occurring events.

PMID- 12230997
TI  - Population studies on three Native Alaska population groups using STR loci.
AB  - Allele distributions for 13 short tandem repeat (STR) loci D3S1358, vWA, FGA,
      D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, TH01, TPOX, CSF1PO and D16S539
      were determined for three Native Alaskan population groups-Athabaskans, Inupiats,
      and Yupiks. Although genetic diversity is lower in the Native Alaskan populations
      compared with Caucasians and Africans, almost all loci are highly polymorphic in
      all three Native Alaskan groups. There was little evidence for departures from
      Hardy-Weinberg expectations (HWE) in any of the populations. Only two examples of
      detectable departures from HWE out of 39 locus-population tests performed were
      observed based on the exact test (Yupik, D8S1179, P=0.030; Yupik, D5S818,
      P=0.016). The F(ST) estimate overall 13 STR loci is 0.0309 for the Native Alaskan
      populations. Based on a genetic distance measure, Athabaskans are more closely
      related to Apaches and Navajos (all of the same linguistic group) than the other
      Native Alaskan groups. The F(ST) estimate for Athabaskans, Apaches and Navajos is
      0.0180 and for Inupiats and Yupiks is 0.0167. The allele frequency data can be
      used for estimating DNA profile frequencies for Native Americans residing in
      Alaska.

PMID- 12230998
TI  - Detection of ABH blood group antigens in the saliva of Koreans and their
      stability according to storage of saliva samples.
AB  - The purpose of the present study was to identify salivary molecules carrying the
      ABH blood group antigens in Koreans and to investigate the changes in these
      antigens according to processing and storage of saliva samples. Secretor or non
      secretor phenotypes and salivary components carrying the ABH antigens were
      identified in 90 subjects, 30 subjects in each ABO blood group, by SDS-PAGE and
      immunoblotting. Saliva samples were then obtained from 12 secretors-two males and
      two females in each ABO blood group and aliquots of both fresh saliva samples and
      their supernatants after centrifugation were stored at room temperature, 4, -20
      and -70 degrees C. The same experiments were performed after 1, 3 and 6 months to
      investigate changes in the blood group antigens. In all 68 secretors, high
      molecular-weight salivary mucin (MG1) was found to be the primary carrier of the
      ABH antigens. A salivary component of approximately 80 kDa also carried H antigen
      in seven saliva samples of 22 blood type O secretors. The blood group antigens
      were better detected in centrifuged samples. In saliva samples preserved at room
      temperature and 4 degrees C, the blood group antigens were either not detected or
      detected as degraded molecules. No change was found in the blood group antigens
      in saliva samples preserved at -20 and -70 degrees C for 6 months.

PMID- 12230999
TI  - STR data for the PowerPlex 16 loci for the Chinese population in Hong Kong.
AB  - Allele frequencies for the 15 STR loci included in the PowerPlex 16 kit were
      obtained from a sample of 247 unrelated Chinese in Hong Kong.

PMID- 12231000
TI  - Genetic profile of the Acores Archipelago population using the new PowerPlex 16
      system kit.
AB  - Allele and haplotype frequencies of 16 chromosome STR loci, 15 of them included
      in the Kit PowerPlex16 System from Promega were determined in a sample of
      unrelated males from the Acores Archipelago. All subjects were subjected to an
      interview in order to make sure that their ancestors belonged to the same island
      at least back to three generations. This way we intended to look for possible
      inter-islands differences. PowerPlex16 includes STRs not studied before in the
      Acores population. The Kit includes two new allele markers (Penta D and Penta E),
      which proved to be extremely useful for paternity testing (PD=0.921 and 0.971,
      respectively). The study revealed that the Acores population is considerable
      different from the previous studied Madeira population, but does not differ from
      that of the north Portugal. Nevertheless, some loci presented alleles not
      previously reported for Portugal.

PMID- 12231001
TI  - Population data of five STRs in three regions from Portugal.
AB  - Allele and haplotype frequencies of five chromosome STR loci (CD4, TPO, FES, TH01
      and VWA) were determined for unrelated males throughout Portugal. This report
      presents STR data for three separate regions of Portugal, being the first time
      that data on the south of the country is presented. This study reveals that the
      three regions from Portugal are not genetically homogeneous. The north of
      Portugal presents significant differences in the CD4 locus, when compared with
      the other two populations. When compared with Madeira and Acores, the three
      regions show a different behavior at TPO and VWA loci.

PMID- 12231002
TI  - Allele distribution data of nine short tandem repeat loci for Turkish population:
      D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820.
AB  - Allele and genotype frequencies for the nine loci D3S1358, vWA, FGA, D8S1179,
      D21S11, D18S51, D5S818, D13S317 and D7S820 were determined for 310 unrelated
      Turkish individuals.

PMID- 12231003
TI  - Genetic profile of a multi-ethnic population from Guine-Bissau (west African
      coast) using the new PowerPlex 16 System kit.
AB  - Allele and haplotype frequencies of 15 chromosome STR loci included in the kit
      PowerPlex16 System from Promega, were determined in a sample of unrelated males
      from Guine-Bissau, a country from the west African coast. All individuals were
      subjected to an interview in order to make sure that their ancestors belonged to
      the same ethnic group. This way we intended to look for possible inter-ethnic
      differences. PowerPlex 16 includes STRs not studied before in any multi-ethnic
      population. The kit includes two new allele markers (Penta D and Penta E), which
      are very useful either in forensics or population genetic studies. The Guinean
      population presents significant differences when compared with other African
      populations.

PMID- 12231006
TI  - The energy-transducing NADH: quinone oxidoreductase, complex I.
AB  - The energy-transducing NADH: quinone (Q) oxidoreductase (complex I) is the
      largest and most complicated enzyme complex in the oxidative phosphorylation
      system. Complex I is a redox pump that uses the redox energy to translocate H(+)
      (or Na(+)) ions across the membrane, resulting in a significant contribution to
      energy production. The need to elucidate the molecular mechanisms of complex I
      has greatly increased. Many devastating neurodegenerative disorders have been
      associated with complex I deficiency. The structural and functional complexities
      of complex I have already been established. However, intricate biogenesis and
      activity regulation functions of complex I have just been identified. Based upon
      these recent developments, it is apparent that complex I research is entering a
      new era. The advancement of our knowledge of the molecular mechanism of complex I
      will not only surface from bioenergetics, but also from many other fields as
      well, including medicine. This review summarizes the current status of our
      understanding of complex I and sheds light on new theories and the future
      direction of complex I studies.

PMID- 12231007
TI  - Cytopathies involving mitochondrial complex II.
AB  - Complex II (succinate-ubiquinone oxidoreductase) is the smallest complex in the
      respiratory chain and contains four nuclear-encoded subunits SdhA, SdhB, SdhC,
      and SdhD. It functions both as a respiratory chain component and an essential
      enzyme of the TCA cycle. Electrons derived from succinate can thus be directly
      transferred to the ubiquinone pool. Major insights into the workings of complex
      II have been provided by crystal structures of closely related bacterial enzymes,
      which have also been genetically manipulated to answer questions of structure
      function not approachable using the mammalian system. This information, together
      with that accrued over the years on bovine complex II and by recent advances in
      understanding in vivo synthesis of the non-heme iron co-factors of the enzyme, is
      allowing better recognition of improper functioning of human complex II in
      diseased states. The discussion in this review is thus limited to cytopathies
      arising because the enzyme itself is defective or depleted by lack of iron-sulfur
      clusters. There is a clear dichotomy of effects. Enzyme depletion and mutations
      in SDHA compromise TCA activity and energy production, whereas mutations in SDHB,
      SDHC, and SDHD induce paraganglioma. SDHC and SDHD are the first tumor suppressor
      genes of mitochondrial proteins.

PMID- 12231008
TI  - Defects in mitochondrial respiratory complexes III and IV, and human pathologies.
AB  - Here, relationships between alterations in tissue-specific content, protein
      structure, activity, and/or assembly of respiratory complexes III and IV induced
      by mutations in corresponding genes and various human pathologies are reviewed.
      Cytochrome bc(1) complex and cytochrome c oxidase (COX) deficiencies have been
      detected in a heterogeneous group of neuromuscular and non-neuromuscular diseases
      in childhood and adulthood, presenting a number of clinical phenotypes of
      variable severity. Such disorders can be caused by mutations located either in
      mitochondrial genes or in nuclear genes encoding structural subunits of the
      complexes or corresponding assembly factors/chaperones. Of the defects in
      mitochondrial DNA genes, mutations in cytochrome b subunit of complex III, and in
      structural subunits I-III of COX have been described to date. As to defects in
      nuclear DNA genes, mutations in genes encoding the complexes assembly factors
      such as the BCS1L protein for complex III; and SURF-1, SCO1, SCO2, and COX10 for
      complex IV have been identified so far.

PMID- 12231009
TI  - Homeopath & patient--a dyad of harmony?
AB  - Within the last 20 yr, heterodox medicine has become increasingly popular in
      western societies. Critics and advocates argue that the physician-patient
      relationship is a key factor to this success. This study which is based on 20
      semi-structured interviews with homeopathic physicians in Berlin questions the
      notion of a purely consensual interaction. While we can find a certain degree of
      partnership between homeopathic physicians and their patients, there is a
      significant amount of negotiation and disagreement as well: The arenas are the
      revelation of the prescribed homeopathic remedy, patients' expectations, the
      physicians' fees and differing views on the appropriate duration of consultation.
      Consequently, a rather complex picture of the physician-patient interaction
      emerges which challenges the notion of a purely harmony- and consumer-oriented
      consultation in heterodox medicine. It does not seem possible straightforwardly
      to apply any of the existing theoretical models to the physician-patient
      relationship.

PMID- 12231010
TI  - Migration and HIV prevention programmes: linking structural factors, culture, and
      individual behaviour--an Israeli experience.
AB  - Migration is one of the structural factors associated with HIV infections, but
      the dynamic and complex role of migrant situations as determinants of HIV-related
      vulnerability is still a major issue for social science research. Moreover,
      interventions to address the specific structural and contextual factors inherent
      in this association are limited and many do not take into account the cultural
      components. This paper presents a multi-level framework for analysis of the links
      between migration and HIV. It includes the association of migration with
      structural macro factors-lower socio-economic status and limited power in the new
      society; intermediate structural factors-limited social capital and bi
      directional interaction of cultural norms; and individual-level factors-stressors
      unique to the migration context, depleted psychosocial resources, loss of
      cultural beliefs and low use of health services. All these factors affect risky
      sexual behaviour and transmission of HIV. The paper utilises those elements of
      the framework that are relevant to the specific needs of immigrant populations
      from the former Soviet Union and from Ethiopia in Israel. We demonstrate their
      application to integrated, multi-level HIV prevention interventions and propose
      several special principles for development of migration-related HIV prevention
      programmes.

PMID- 12231011
TI  - Cross-cultural encounters between careproviders: rabbis' referral letters to a
      psychiatric clinic in Israel.
AB  - This paper explores the meaning and social functions of referral letters sent to
      a mental health clinic in Israel by Haredi (ultra-orthodox) rabbis. The letters
      exemplify social mechanisms by which various institutions and individuals
      (careproviders, therapists, and other social actors) negotiate different
      therapies, advice, and interventions in cross-cultural encounters. We argue that
      beyond the practical functions of the letters, the rabbis-representatives of a
      "popular" and religious social sphere-use them to negotiate their position in
      relation to the psychiatric clinic as a representative of a professional and
      secular sphere. We show that the rabbis "submit" to the professional and secular
      therapists by using a local adaptation of Western psychological and psychiatric
      discourses (instead of a religious or mystical discourse), but also that by
      choosing a letter as their preferred medium of communication (instead of a
      personal visit to the clinic), they distance themselves from it. We suggest that
      the rabbis reconstitute, via the letters, social boundaries within their
      religious community and between their community and secular society. Hence,
      through analysis of discourses of mental illness in a cross-cultural encounter we
      examine ways in which illness is practically managed among diverse groups in
      society. Specifically, we analyze such discourses as part of a power relationship
      between careproviders who belong to different therapeutic social spheres, using a
      phenomenological exploration of how mental illness is perceived and constructed
      as both "a medical problem" and as "social deviance".

PMID- 12231012
TI  - Researching sexual and reproductive behaviour: a peer ethnographic approach.
AB  - In recent years, ethnographic research has challenged the notion within
      demography that fertility-related behaviour is the outcome of individualistic
      calculations of the costs and benefits of having children. Anthropology has
      further criticised the abstraction in demographic analysis of sexual behaviour
      and fertility decision-making from the socio-cultural and political context in
      which the individual or couple is located. Within demography itself,
      institutional and political-economic analyses have argued strongly that sexual
      and reproductive behaviour must be understood within locally specific social,
      cultural, economic and political contexts. Positivist and empiricist research
      methods, such as the sample survey and focus groups, which continue to dominate
      demographic inquiry and applied research into sexual and reproductive behaviour,
      have been shown to be limited in their ability to inform about the process of
      behaviour change and contexts within which different behaviours occur. The
      article introduces a new methodology for researching sexual and reproductive
      behaviour, called the peer ethnographic approach, which the authors have
      developed in an attempt to address some of the limitations of the methods which
      currently dominate research into sexual and reproductive behaviour. The peer
      ethnographic methodology is discussed in detail and the results of recent field
      testing are reported, which show that, although the approach has limitations, it
      also has the potential to make a significant contribution to our understanding of
      sexual and reproductive behaviour.

PMID- 12231013
TI  - The lesser shame: abortion among educated women in southern Cameroon.
AB  - Educated women in southern Cameroon both condemn abortion and practice it with
      some regularity. This apparent paradox arises because educated Cameroonian women
      use abortion as one of a set of strategies to manage the timing and social
      context of entry into motherhood. This paper is based on a body of research which
      included a demographic life history survey (N = 184), open-ended narrative
      interviews (N = 37), and participant observation over 10 months. The survey data
      included 61 reported abortions, giving a lower-bound estimate of the crude
      abortion rate of 19 per thousand woman-years of life. In southern Cameroon,
      sexual activity is socially tolerated in a wide variety of non-marital
      relationships, while childbearing is not. Thus, most of my informants, including
      those who reported having aborted, say that abortion is shameful; however, they
      view its moral and social consequences as less grave than those of a severely
      mistimed entry into socially recognized motherhood. That is, abortion persists in
      southern Cameroon because it is the lesser shame.

PMID- 12231014
TI  - Adolescent understandings of political violence and psychological well-being: a
      qualitative study from Bosnia Herzegovina.
AB  - The Harvard Trauma Questionnaire and Hopkins Symptoms Checklist (HSCL-25) were
      given to 337 13-15 year olds who had lived through the recent war in Bosnia
      Herzegovina, on opposite sides of the conflict. A gender-balanced sub-sample of
      40 adolescents was selected on the basis of their combined symptom scores,
      including equal numbers of high and low scorers from each side. A year of
      participant observation in two cities and in-depth interviews were conducted with
      the sub-sample to explore their understandings of the war and their subjective
      perceptions of their psychological well-being. Case studies are presented to show
      that the degree to which an adolescent engaged in a search for meaning to the
      conflict is related to their psychological well-being. Searching for meaning did
      not appear to be protective. Less well adolescents in both cities were more
      engaged in searching for meaning. Well adolescents appeared to be more
      disengaged. Searching for meaning appeared to be associated with sensitivity to
      the political environment, and feelings of insecurity about the prospect of a
      future war. The particular local context had an important effect in mediating the
      manner in which disengagement and engagement occurred. These findings suggest
      that the more avoidant methods of coping with political violence warrant further
      investigation. Political engagement may be protective in low-level conflicts
      where there is a possibility for action. When there is little opportunity for
      active engagement, the search for meaning has a different effect. Adolescents
      engaged in the search for meaning recognise that their recovery is bound up with
      the recovery of their communities as a whole. Assistance and support may have to
      address the material, social and political difficulties that the search uncovers.

PMID- 12231015
TI  - Social capital and violence in the United States, 1974-1993.
AB  - Social capital is a characteristic of communities. Cross-sectional studies have
      shown that social capital is inversely associated with homicide and violent
      crime. We hypothesized that variations in social capital in US states over time
      can predict variations in regional homicide mortality both across and within time
      periods. We analyzed serial cross-sectional data for measures of social capital
      and age-adjusted homicide rates between 1974 and 1993. We used perception of
      social trust and per capita membership in voluntary associations, obtained from
      responses to the General Social Surveys, as the principal measures of social
      capital. We controlled for potential confounding by mean levels of income,
      urbanization, and region. Measures of perceived trust were strongly inversely
      correlated with homicide rates in an aggregate cross-sectional analysis (r=-0.51,
      p<0.001) and also within each time period. Social capital was an independent
      predictor of rates of violence when controlling for income, region, and
      urbanization (p<0.001). Homicide rates also predicted levels of social capital in
      adjusted models (p<0.001). To investigate directionality of this relationship we
      developed Markov transition matrices that described the change in the states'
      levels of social capital and homicide across time intervals. Analysis of the
      transitional probabilities confirmed that a simple unidirectional association
      between social capital and violence was not sufficient to describe this
      association. There is likely an impact of violence on levels of perceived trust
      in communities that complements the hypothesized effect of social capital on
      homicide. We conclude that the relationship between social capital and violence
      over time is non-linear and dynamic. More complex analytic models describing the
      relationship between violence and ecological social determinants need to be
      considered.

PMID- 12231016
TI  - Who's at risk? Factors associated with intimate partner violence in the
      Philippines.
AB  - We describe the individual and household characteristics associated with intimate
      partner violence (IPV) in the Philippines, using data from the Cebu Longitudinal
      Health and Nutrition Survey (CLHNS). We also examine 56 in-depth interview
      transcripts to explore the context of IPV. We focus our analysis on patterns of
      household decision-making as a measure of the interpersonal dynamics between
      husbands and wives. Thirteen percent of women in our sample reported IPV. While
      economic factors are often implicated in the cycle of violence in households, we
      find employment status and relative earnings do not predict IPV. Lower levels of
      household wealth and urban residence are associated with a higher likelihood of
      IPV. Patterns of household decision-making emerge as strong predictors of
      violence. The greater the number of decision-making domains men dominate, the
      more likely they are to use IPV; however, we also find that when women dominate
      household decisions, they are also more likely to experience IPV. Only 6% of
      women reported IPV when all household decisions were made jointly compared to 25%
      when no decisions were made jointly.

PMID- 12231018
TI  - Self-rated economic condition and the health of elderly persons in Hong Kong.
AB  - Studies have documented that health and income are important variables affecting
      the quality of life in old age. However, there is little knowledge about whether
      perceived financial sufficiency affects the health of elderly persons. Recent
      research has documented that in addition to material and behavioural
      determinants, psychosocial pathways also have an influence on health
      inequalities. This is the first paper to examine the relation between self-rated
      economic condition (measured with a single item question) and reported health
      conditions (i.e., somatic complaints, diagnosed physical diseases, functional
      health (Activities of Daily Living), self-rated health, and mental health status
      (General Health Questionnaire-30 [GHQ-30]) among elderly persons in Hong Kong.
      The respondents of the study were persons aged 65 and over residing in public
      housing estates in the Southern District of Hong Kong Island. Four hundred and
      fifty respondents were interviewed in 1995 by means of a structured
      questionnaire. The study found that although it did not record the actual income
      levels of the respondents, the subjective measure vividly demonstrated the health
      differentials among the elderly respondents. Multiple regression analyses
      suggested that self-rated economic condition was a significant predictor of the
      number of somatic complaints and physical illnesses reported, as well as of
      functional health, self-rated health, and mental health status (controlling for
      socio-demographic variables). However, the measure explained a higher proportion
      of variance in models related to psychological health than those related to
      physical health. The findings substantiated the role of psychosocial processes in
      understanding perceived health and illness and health inequalities in particular.

PMID- 12231017
TI  - Physician evaluation of obesity in health surveys: "who are you calling fat?".
AB  - Previous research on status generalization suggests that physicians may use non
      medical factors in their evaluation, interpretation, and treatment of persons
      presenting for care. This study compares physicians' evaluations of obesity with
      physical measurements of body stature and fat collected from a large national
      health examination survey. While the anthropometric measures are strong
      predictors of physician evaluations of obesity, between 13% and 19% of the
      respondents were classified in ways that could not be predicted from the
      anthropometric measures. Moreover, personal and status characteristics were
      related to physicians' evaluations of obesity. Women, especially White and taller
      women, were more likely to be evaluated as obese than would be predicted from the
      anthropometric measures-African American women were less likely than their White
      counterparts to be so classified. Physicians' evaluation of obesity was least
      consistent with measured obesity for older respondents. Indeed among men, age was
      the most important status characteristic shaping physician evaluations: older men
      were more likely to be evaluated as obese. The findings suggest that the cluster
      of status characteristics is important to physicians during medical evaluations.

PMID- 12231019
TI  - The instrumental uses of autonomy: a review of AIDS law and policy in Europe.
AB  - This paper reviews the changing role of the ethical value of autonomy in law and
      policy relating to AIDS in a number of European jurisdictions. In the early years
      of the epidemic the autonomy of infected and at-risk persons, and of social
      groups was promoted as a means of reducing the spread of HIV in the general
      population. Accordingly, autonomy was deemed worthy of respect for instrumental
      reasons. This means-end calculation was premised on the lack of medical
      therapies, as well as the need to avoid discrimination in order to prevent at
      risk persons from "going underground". In law, this instrumentalisation of
      autonomy was reflected in a specific application of the proportionality test
      applied in administrative and human rights law, that is, imposing coercive or
      discriminatory measures would be disproportionate, or even inimical, to the goal
      of reducing the spread of HIV. This was a contingent analysis, strongly informed
      by the state of medical knowledge at the time, as well as by the relative power
      of professionals, health bureaucrats and lay activists. With the introduction of
      effective therapies such as the Highly Active Retroviral Therapy and Zidovudine,
      the terms of the proportionality analysis have changed decisively. As a result,
      it is now more likely than before that coercive measures will be implemented.

PMID- 12231020
TI  - Barriers, facilitators, and access for wheelchair users: substantive and
      methodologic lessons from a pilot study of environmental effects.
AB  - We undertook a month-long intensive pilot study of a sample of adult wheelchair
      users in Boston, Massachusetts and Durham, North Carolina, USA. The study had
      four objectives; to: (1) measure experiences of reaching and failing to reach
      specific destinations; (2) measure encounters with environmental facilitators and
      barriers, including both those overcome and not overcome; (3) determine the
      frequencies of destinations, facilitators, and barriers, and (4) test for
      consistency between daily reports and retrospective reports. Full participation
      entailed baseline and exit telephone interviews, and 28 daily telephone contacts.
      Participants reported reaching a wide range of destinations, most notably, banks,
      stores and shops, friends' and relatives' homes and health professionals'
      offices. There was a smaller range of destinations that they could not reach,
      despite trying; most notably, religious buildings, friends' and relatives' homes
      and work-places. They encountered an array of barriers, some of which they were
      able to overcome and others they could not overcome. Reported barriers included
      personal, interpersonal, and environmental barriers. The 25 subjects completing
      the study reported a wide range of human, environmental, and technologic support.
      In general, the consistency among daily, baseline, and exit interviews was high.
      This study has both substantive and methodologic implications. It suggests that
      efforts to facilitate social participation by wheelchair-users should focus not
      only on the built environment, but also on interventions in personal assistance
      and assistive technology, health promotion and fitness, and programs that improve
      civility. Methodologically, the data suggest that it is possible to make reliable
      measures of environmental encounters without the administrative and respondent
      burden associated with daily interviews.

PMID- 12231021
TI  - The changing nature of contracts in German health care.
AB  - The flexibility inherent in the German health care system is fairly limited. The
      contracting environment itself is characterized by bilateral cartels negotiating
      the terms covering their respective members. Looking at some recently implemented
      reforms, namely structural contracts and experimental settings, the paper
      assesses the potential for sickness funds to take on a more active role. The
      paper also evaluates the implications for the contracting relationships between
      the statutory sickness funds and provider associations. Furthermore, the
      potential effect of selective contracting on the health care system is studied. A
      look at the reforms recently enacted in other countries illustrates the
      difficulties contractual reform has to cope with in an environment characterized
      by strong informational asymmetries. It is postulated that both private and
      public choices are needed for a successful reform effort.

PMID- 12231022
TI  - Neighborhood structural characteristics and mental disorder: Faris and Dunham
      revisited.
AB  - We examined the relationship between neighborhood structural characteristics and
      mental disorder using data from the National Institute of Mental Health's
      Epidemiological Catchment (ECA) surveys (n = 11,686). After controlling for
      individual-level characteristics, we found that neighborhood disadvantage was
      associated with higher rates of major depression and substance abuse disorder,
      and that neighborhood residential mobility was associated with higher rates of
      schizophrenia, major depression, and substance abuse disorder. Implications for
      future research on the social ecology of mental disorder are discussed.

PMID- 12231023
TI  - 'Could you please pass one of those health leaflets along?': exploring health,
      morality and resistance through focus groups.
AB  - This paper derives from research in which focus groups were used as a preliminary
      method of eliciting peoples' perceptions, attitudes and opinions towards health
      and health promotion in a Northern British city. However, applying criticisms
      associated with social constructionist theories (e.g. discourse analysis and
      rhetorical analysis), some recently emerging work on focus groups (see The
      challenge and promise of focus groups, in: Barbour, Kitzinger (Eds.), Developing
      Focus Group Research: Politics, Theory and Practice, Sage, London, 1999, p. 1;
      Focus Groups in Social Research, Sage, London, 2001) has suggested that their
      traditional use, as a kind of 'window' onto peoples' attitudes and opinions,
      misses important dimensions of the way in which these phenomena are actively
      negotiated and constructed during the course of the focus group. Working on the
      premise that these observations are particularly pertinent to health issues, this
      paper draws on data from one focus group in order to provide a detailed working
      example of the way in which attitudes and opinions towards health issues are
      actively constructed during the course of interaction. In addition, in accordance
      with social constructionist theories, attention will be paid to the way in which
      such construction is inextricably linked to social and moral actions such as the
      negotiation of blame and allocation of responsibility. Through an analysis of six
      extracts, the paper ultimately identifies three 'positions' or 'stances', which
      develop over the course of the focus group, often in opposition to one another.
      These are: (1) 'positive mental attitude'; (2) 'genes and luck'; and (3)
      'resistance'. Each of these positions becomes associated, not only with certain
      moral values, but also 'attached' to certain people within the group. One of the
      main aims of this analysis is to illustrate how, through the everyday nature of
      such debates, health remains an intrinsically moral phenomenon.

PMID- 12231025
TI  - The use of learning contracts in mental health nursing clinical placement: an
      action research.
AB  - This paper examines the implementation of learning contracts with a cohort of
      undergraduate nursing students in Hong Kong during a mental health nursing
      clinical placement. An action learning approach was used by the researchers. Data
      collection methods included questionnaires and semi-structured interviews.
      Results showed that students' autonomy and motivation in clinical learning
      increased through the use of learning contracts. There was more sharing between
      students and teachers and the quality of teaching and learning was improved. The
      report concludes that contract learning should be integrated into the curriculum
      of nurse education as a learning strategy for nursing students.

PMID- 12231024
TI  - Complementary/alternative medicine in chronic illness as informed self-care
      decision making.
AB  - The reasons that persons with chronic illness explore complementary and
      alternative medicine (CAM) have not been well understood. Using data from a study
      of self-care decision making in chronic illness, we conducted a qualitative
      secondary analysis to interpret the rationale underlying decisions to experiment
      with and use various CAM practices and products. The findings confirm that CAM
      use can be understood as a critical component of self-care management in general,
      and not as a rejection of conventional medicine or an unrealistic search for
      cure. In contrast, it represents personal responsibility for health, reframing
      the measures by which therapeutics are evaluated, and adopting a pragmatic
      approach to living as well as possible in the context of a chronic condition.

PMID- 12231026
TI  - Dietary and fluid compliance in Chinese hemodialysis patients.
AB  - The current cross-sectional study examined dietary and fluid compliance behaviors
      in Chinese hemodialysis (HD) patients and identified variables related to
      compliance. Sixty-two chronic HD patients participated and information was
      obtained about their knowledge of dietary and fluid restrictions related to
      dialysis, health beliefs, personal and medical characteristics, and self-reported
      compliance. In addition, serum levels of potassium (K) and phosphate (PO(4)) and
      interdialytic daily weight gain were retrieved from the medical records. Dietary
      and fluid compliance was observed in only 35.5% and 40.3% of the patients,
      respectively. No direct relationship was observed between dietary knowledge and
      any compliance measures. 'Perceived barriers' was the only variable of the health
      belief model that showed associations with the compliance measures, implying that
      patients who perceived less barriers in following the dietary instructions showed
      better compliance. Residual urine output volume was positively correlated with
      the level of fluid compliance. Patients with more hours on HD per week were found
      to be more fluid noncompliant. Working patients and those whose diet was prepared
      by someone else in the family were also more likely to be noncompliant. Health
      professionals should be aware of the factors behind noncompliance in HD patients
      and assist them in making life-style changes. Patient education with family
      involvement, identification of at-risk patients for noncompliance and assisting
      patients to identify and manage difficulties with life-style changes related to
      HD are important elements in promoting compliance.

PMID- 12231027
TI  - Family functioning in the context of chronic illness in women: a Korean study.
AB  - The aims of this study were to clarify the concept of family functioning in the
      context of a female family member's chronic illness, and to describe the
      processes by which the housewife copes with the situation. The study applied the
      hybrid model of concept development, which consists of three phases: theoretical,
      empirical, and analytic. In the theoretical phase, a working definition of family
      functioning was established and the dimensions of family functioning and
      subconcepts were identified through an extensive review of the literature. In the
      empirical phase, in-depth interviews with members of six normal families and
      seven families in which the housewife had a long-term diagnosis of rheumatoid
      arthritis were carried out in order to gain descriptions of family functioning in
      both contexts, and to assess how the housewife coped with her illness in relation
      to family functioning. The final analytic phase identified the differences and
      similarities in family functioning between the normal family and family with a
      chronically ill housewife. A refined definition of family functioning emerged
      that identified the concept in terms of a complex set of functional dimensions
      comprising affective, structural, control, cognitive, and external relationships.
      The data revealed that family functioning is dynamically changed when the
      housewife becomes ill with a chronic disease. Three types of adaptation process
      were identified by which the housewives adapted to family functioning in the
      context of their chronic illnesses: negotiated, self-accommodating, and separated
      enduring. The implications of these findings for research and nursing practice
      are discussed.

PMID- 12231028
TI  - The effects of support groups on caregivers of patients with schizophrenia.
AB  - The purpose of this study was to assess the effects of support groups on
      caregivers of patients with schizophrenia. This was a time series nonequivalent
      control group design. Subjects were evaluated in three waves of data collection:
      before intervention, after intervention and one-month follow-up. The support
      group's effects were measured using changes in the subjects' perceived levels of
      burden, depression status and satisfaction about their participation in the
      program. Professionally led support group had a close and time-limited format.
      The GEE (generalized estimated equation) revealed differences in caregivers'
      level of burden and depression status between the support and control groups in
      the post-test and one-month follow-up. The differences highlighted the fact that
      participation in support groups provides more effective assistance to caregivers
      than the control group.

PMID- 12231029
TI  - The construct validity of a rating scale designed to assess spirituality and
      spiritual care.
AB  - A postal survey, containing a questionnaire and covering letter, was distributed
      to 1029 ward-based nurses, of all grades, in a Large NHS Trust in an attempt to
      establish how nurses perceived spirituality and spiritual care. A response rate
      of 55.3% (n = 549) was obtained. Part of the questionnaire contained "The
      Spirituality and Spiritual Care Rating Scale" (SSCRS) a newly constructed
      instrument to aid the investigation and measurement of Spirituality and Spiritual
      Care. Factor Analysis was performed in an attempt to establish construct validity
      and to identify any underlying associations between items in the scale. It
      suggested a 17-item instrument with four factor-based subscales: Spirituality,
      Spiritual Care, Religiosity and Personalised Care. The 17-item SSCRS demonstrated
      a reasonable level of internal consistency reliability, having a Cronbach's alpha
      coefficient of 0.64. Confirmatory Factor Analysis is recommended in order to
      cross-validate and refine this new Rating Scale.

PMID- 12231030
TI  - Reasons for physically restraining patients and residents: a systematic review
      and content analysis.
AB  - OBJECTIVE: The purpose of this systematic review was to determine why people are
      physically restrained in the acute and residential care settings. METHOD: A
      comprehensive search was undertaken of electronic databases to identify studies
      addressing the reasons for using physical restraint. Findings were synthesised
      using content analysis. RESULTS: Twenty-three studies were identified. The most
      common reason for using restraints related to patient-oriented issues such as
      ensuring the safety of people. However, they are also commonly used to facilitate
      treatment, maintain the social environment and because of issues such as
      understaffing.

PMID- 12231031
TI  - The relationship between quality of life, sense of coherence and self-esteem in
      persons after coronary artery bypass graft surgery.
AB  - We examined the contribution of Antonovsky's sense of coherence in explaining the
      variance of quality of life (QOL) in 84 patients 1-2 years following coronary
      artery bypass graft surgery. The hypothesis was: after controlling for variables
      related to poor health vulnerability, perceived support, self-esteem, and chronic
      illness trajectory instability and work, the addition of sense of coherence will
      significantly add to the explained variance of quality of life. The first two
      variables explained 49% of the variance of the QOL scale. Adding perceived social
      support, self-esteem and sense of coherence increased explained variance to 64%,
      69%, and 75%, respectively. These findings supported our hypothesis.

PMID- 12231032
TI  - The educational preparation of undergraduate nursing students in pharmacology:
      perceptions and experiences of lecturers and students.
AB  - This paper explores the perceptions and experiences of lecturers and
      undergraduate nursing students relating to teaching and learning issues in
      pharmacology. A total of 14 focus group interviews were conducted at 10
      university settings, which involved seven academic staff and seven student
      interviews. The focus group interviewing method was used because it enabled all
      participants to have 'a say', facilitated the expression of diverse views, and
      allowed participants to express themselves without fear that their views would be
      openly criticised. Student participants comprised second and third year
      undergraduate nurses while lecturer participants involved course coordinators,
      subject coordinators, and bioscience and nursing lecturers. The 'framework'
      method was used for data analysis, which involved the following stages:
      familiarisation, identifying a thematic framework, indexing, charting, and
      finally, mapping and interpretation. Four major themes emerged from discussions
      with lecturers and students: teaching considerations, learning considerations,
      the relationship between pharmacology knowledge and clinical practice, and the
      features of an 'ideal' programme in pharmacology. The findings highlighted that
      potential conflicts existed among academic staff relating to the balance of
      pharmacology and nursing content in curricula, which often led to over-laden
      curricula. Potential conflicts also existed between lecturers and students about
      the value placed on a separate pharmacology subject as opposed to an integrated
      pharmacology programme. In summary, there is still much scope for educational
      initiatives to improve students' knowledge of pharmacology and medication
      management.

PMID- 12231037
TI  - Contemporary patterns of androgen deprivation therapy use for newly diagnosed
      prostate cancer.
AB  - Although once reserved for the management of metastatic prostate cancer, androgen
      deprivation therapy (ADT) is being used increasingly to treat lower stages of
      disease. We sought to assess patterns of ADT use in a contemporary cohort of men
      newly diagnosed with prostate cancer. Men with newly diagnosed prostate cancer
      who had > or =12 months of follow-up evaluation were identified in a national
      disease registry of patients with prostate cancer. The patterns of ADT use, both
      primary and secondary, were characterized and stratified by risk according to
      prostate-specific antigen levels, clinical stage, and Gleason score. In a cohort
      of 1485 men, 46% underwent ADT at some point during their treatment: 41% as
      primary therapy (either sole therapy or neoadjuvant therapy), and 5% as secondary
      therapy. In all, 50% of men receiving initial ADT had low- or intermediate-risk
      disease characteristics. Among patients treated with radical prostatectomy and
      radiation therapy, neoadjuvant ADT was administered in 20% and 48% of patients,
      respectively. Secondary hormonal manipulation was observed in 5% and 7% of
      patients treated initially with surgery or radiation, respectively. ADT is
      commonly used to treat men with prostate cancer. Much of the use of ADT is in men
      with low- and intermediate-risk disease characteristics. The appropriateness of
      such therapy requires further study, including its effect, not only on disease
      endpoints, but also on resource utilization and health-related quality of life.

PMID- 12231036
TI  - Overview consensus statement. Newer approaches to androgen deprivation therapy in
      prostate cancer.

PMID- 12231039
TI  - Emerging role of adjuvant hormonal therapy.
AB  - Recent years have seen a downward shift in the most common disease stage at
      diagnosis and in the age of patients diagnosed with prostate cancer. Although
      younger men with clinically localized disease are generally offered radiotherapy
      or radical prostatectomy, such treatment does not always produce a cure. Adjuvant
      hormonal therapy (medical or surgical castration) has been shown to extend
      progression-free survival in both the radiotherapy and surgical settings, and
      overall survival benefits have also been demonstrated in some studies. However,
      castration is associated with sexual dysfunction that may be unacceptable,
      particularly among younger patients. The ongoing bicalutamide (Casodex;
      AstraZeneca Pharmaceuticals, Wilmington, DE) Early Prostate Cancer program is
      evaluating the efficacy and tolerability of bicalutamide 150 mg as immediate
      therapy, either alone or as an adjuvant to therapy of curative intent, in
      patients with localized or locally advanced prostate cancer. This is the largest
      clinical trial program in prostate cancer treatment to date, comprising 3
      randomized, double-blind, placebo-controlled studies with a total of 8113
      patients. At median follow-up period of 3 years and after 922 progression events,
      the bicalutamide group had a significant reduction of 42% in the risk of
      objective progression compared with patients who received placebo plus standard
      care. The risk of prostate-specific antigen progression was also significantly
      reduced by 59%. As expected, gynecomastia and breast pain were the most
      frequently reported side effects of bicalutamide therapy. A longer follow-up
      period will determine whether the reduced risk of progression will translate into
      cause-specific and overall survival benefit for these patients.

PMID- 12231041
TI  - Impact of androgen deprivation therapy on survival in men treated with radiation
      for prostate cancer.
AB  - A number of retrospective and randomized trials have studied the effect of
      external-beam radiation therapy (EBRT) plus androgen deprivation therapy (ADT) on
      locally advanced/high-risk prostate cancer. Of 6 published randomized trials that
      have compared EBRT plus ADT with EBRT alone, 2 have shown a highly significant
      overall survival benefit for EBRT plus ADT, and 2 have demonstrated an advantage
      for the combination in patient subsets based on Gleason score. The results from
      the positive trials of EBRT plus ADT versus EBRT alone, as well as a recent
      report of a comparison of short-term (6 months) ADT plus EBRT versus long-term
      (>6 months) ADT plus EBRT, suggest that short-term ADT plus EBRT preferentially
      lengthens the survival of patients with Gleason score 2 to 6 disease, whereas for
      Gleason score 8 to 10 disease, prolongation of survival requires long-term ADT
      plus EBRT. These data are far from clear-cut because there are factors that
      confound interpretation of the subgroup analyses. Retrospective data on patients
      with positive lymph node status support the assertion that EBRT plus ADT prolongs
      survival to a greater degree than either treatment given individually. The weight
      of the available investigations on the survival effect of EBRT plus ADT supports
      its use on a routine basis for patients with high-risk prostate cancer. The
      results with long-term ADT are much more convincing than short-term ADT, and, as
      a consequence, 2 to 3 years are recommended.

PMID- 12231043
TI  - Radiation and hormonal therapy for locally advanced and clinically localized
      prostate cancer.
AB  - Patients with locally advanced prostate cancer (TNM clinical stage T3, T4) who
      were treated using external-beam radiotherapy (EBRT) and 3 years of androgen
      deprivation therapy (ADT) were compared with patients treated with EBRT alone and
      were shown to have a survival benefit. Studies that address the same question for
      patients with clinically localized disease (stage T1, T2) have been completed and
      are awaiting follow-up study. A rate of decrease in the serum hemoglobin level of
      > or =1 g/dL during the first month of neoadjuvant ADT predicted for a
      significantly worse disease-free survival outcome, as defined by the prostate
      specific antigen, for patients with intermediate- and high-risk clinically
      localized disease who were undergoing EBRT and ADT. Validation of this predictive
      factor by others is needed.

PMID- 12231045
TI  - The role of androgen deprivation therapy combined with prostate brachytherapy.
AB  - Several prospective randomized clinical trials have demonstrated improved
      outcomes in men receiving androgen deprivation therapy (ADT) in combination with
      definitive local therapy (external-beam radiotherapy or surgery). ADT is commonly
      combined with prostate brachytherapy (PB) to "downsize" the prostate gland. As PB
      is increasingly used, more men are being treated with a combination of ADT and
      PB. The purpose of this article is to review the effects of ADT in men treated
      with PB. A structured literature review was performed. The effects of ADT on 3
      separate outcomes were examined: (1) volume of the prostate gland, (2) treatment
      related morbidity, and (3) disease-free survival. No prospective randomized
      trials addressing the effects of ADT combined with PB were discovered. There is
      evidence that prostate volume is reduced by 25% to 40% after 3 months of ADT.
      There is some evidence that ADT may be associated with increased acute urinary
      morbidity and decreased erectile function after PB. There is little evidence that
      disease-free survival in men treated with PB is improved with the addition of
      ADT. Neoadjuvant ADT before PB reduces prostate volume. ADT may lead to increased
      acute urinary morbidity and decreased erectile function after PB. No substantial
      effects of ADT on disease-free survival are apparent. Prospective randomized
      trials of PB and ADT are required.

PMID- 12231047
TI  - Preoperative neoadjuvant androgen withdrawal therapy in prostate cancer: the
      Canadian experience.
AB  - The goal of radical prostatectomy is the complete removal of all cancer cells--no
      more, no less. Unfortunately, this is not always possible, especially in men with
      higher risk pathologic features. It is recognized that preoperative staging
      underestimates the extent of disease in < or =66% of cases, and that positive
      margin rates may be as high as 30% to 60%. Over the past 7 years in Canada,
      researchers have been investigating therapies that optimize the complete
      extirpation of all cancer cells with a minimum of morbidity and mortality. An
      example of this therapy is the combined modality approach of shrinking the
      prostate and tumor with androgen withdrawal therapy before surgical removal. The
      availability of potent, reversible, and well-tolerated forms of medical
      castration, and the sensitivity of serum prostate-specific antigen as a marker of
      response to therapy, makes neoadjuvant hormone therapy before localized therapy
      possible and appealing. In this article, we will review the Canadian experience,
      from the laboratory to the clinic.

PMID- 12231049
TI  - Intermittent androgen suppression in prostate cancer: the Canadian experience.
AB  - The role of androgen withdrawal is well established in the treatment of advanced
      prostate cancer. In metastatic cancer the response rate is 70% to 80%, with a
      median duration of progression-free survival of 12 to 33 months and a median
      duration of overall survival of 23 to 37 months. There are limitations to the
      continuous use of androgen withdrawal therapy, including significant adverse
      effects with long-term use. More significantly, the cell death process induced by
      androgen ablation fails to eliminate the entire malignant cell population;
      recurrent tumors are characterized by androgen-independent growth. The concept of
      intermittent androgen suppression proposes that the maintenance of apoptotic
      potential by successive rounds of androgen withdrawal and replacement might
      forestall tumor progression. Intermittent therapy offers quality-of-life benefits
      during the off-therapy period, as well as reduced cost of treatment. This article
      will review the >15 years of Canadian experience with intermittent androgen
      suppression.

PMID- 12231051
TI  - Patterns of failure after primary local therapy for prostate cancer and rationale
      for secondary therapy.
AB  - The timing and type of treatment for patients with biochemical disease recurrence
      after local therapy for prostate cancer remains controversial. This is because of
      many unresolved issues surrounding the natural history of disease progression in
      such patients, including the limited ability of clinical measures to accurately
      define local versus distant disease recurrence. Clinicians generally rely on
      clinical tumor characteristics, such as tumor stage, grade, and prostate specific
      antigen (PSA) kinetics after local therapy, to distinguish local from distant
      recurrence. This determination is important, because patients with local
      recurrence may be candidates for a second, potentially curative treatment,
      whereas those with distant recurrence are generally treated with androgen
      deprivation therapy (ADT). Data from a national disease registry of patients with
      prostate cancer, the Cancer of the Prostate Strategic Urologic Research Endeavor
      (CaPSURE), suggest that the use of secondary cancer treatment after local therapy
      for prostate cancer is common. For patients initially treated with radical
      prostatectomy, secondary treatment appears to be nearly equally divided between
      postoperative radiation and ADT, whereas >90% of patients receiving a secondary
      treatment after radiation are treated with ADT. Serum PSA at diagnosis, Gleason
      score, and type of initial treatment appear to be predictors of secondary
      treatment use in this setting. Patient age, lymph node status, and margin status
      appear to be predictors of secondary treatment with ADT or radiation for patients
      initially treated with radical prostatectomy.

PMID- 12231053
TI  - Antiandrogen monotherapy: indications and results.
AB  - Many patients with prostate cancer for whom hormonal therapy is indicated are
      still physically and sexually active; quality of life is therefore a vital issue
      when considering treatment options. Traditional castration-based therapies,
      although effective, have implications with respect to quality of life, causing
      loss of libido, impotence, fatigue, and reduced bone mineral density. Monotherapy
      with a nonsteroidal antiandrogen is an attractive therapeutic alternative to
      castration, offering effective therapy with potential quality-of-life benefits.
      Of the available nonsteroidal antiandrogens, bicalutamide has been most
      extensively evaluated in the monotherapy setting. Mature combined data (56%
      mortality) from 2 large randomized studies show no statistically significant
      difference in overall survival between bicalutamide 150-mg monotherapy and
      castration in patients with locally advanced, nonmetastatic (stage M0) disease.
      Survival outcome in patients with metastatic (stage M1) disease (43% mortality)
      favored castration, although the difference in median survival between the groups
      was only 6 weeks. Bicalutamide 150-mg monotherapy was associated with significant
      advantages compared with castration, in terms of sexual interest and physical
      capacity, in patients with either M0 and M1 stage disease. Data from a small
      subgroup of patients with stage M0 disease suggest that bicalutamide may also
      reduce the risk of osteoporosis compared with castration. Long-term therapy with
      bicalutamide 150-mg monotherapy is generally well tolerated, with a predictable
      side-effect profile. The most common side effects are male breast pain and
      gynecomastia. Emerging evidence also supports the use of bicalutamide 150 mg,
      both as immediate monotherapy and as adjuvant therapy in early stage (localized
      or locally advanced) prostate cancer.

PMID- 12231054
TI  - A review of measurement of patient preferences for treatment outcomes after
      prostate cancer.
AB  - The diagnosis of early-stage prostate cancer cases creates dilemmas for many men
      diagnosed with the disease each year. Treatment interventions are all associated
      with significant treatment morbidity, including impotence and incontinence. The
      basic concept behind patient preferences, or utilities, is to ask patients to
      make judgments about the value of particular health outcomes. Several preference
      based instruments are available, including the visual analog rating scale, the
      time trade-off utility assessment, and the standard gamble. These assessments
      result in scores or weights assigned to different health states. From the
      perspective of the patient with prostate cancer, the treatment that produces
      optimal outcomes will depend on the relative importance of several domains, which
      may include pain, urinary functioning, sexual functioning, and general physical
      health. Patients with similar diagnoses and overlapping clinical characteristics
      may have markedly different preferences for treatment outcomes.

PMID- 12231056
TI  - Osteoporosis during androgen deprivation therapy for prostate cancer.
AB  - Osteoporosis is an important complication of androgen deprivation therapy (ADT).
      ADT by either orchiectomy or treatment with a gonadotropin-releasing hormone
      agonist decreases bone mineral density and increases fracture risk. Other
      factors, including diet and lifestyle, may contribute to bone loss in men with
      prostate cancer. Routine osteoporosis screening in men with prostate cancer is
      appropriate based on the high prevalence of osteoporosis. There is limited
      information about the best strategy to treat or prevent bone loss during ADT.
      Lifestyle modification, including smoking cessation, moderate alcohol
      consumption, and regular weight-bearing exercise should be encouraged.
      Supplemental calcium and vitamin D are also recommended. Additional treatment is
      warranted for men with osteoporosis, fractures, or high rates of bone loss during
      ADT. Pamidronate, an intravenous bisphosphonate, prevents bone loss during ADT.
      Other bisphosphonates are probably effective, although they have not been
      evaluated in this clinical setting. Alternative forms of hormonal therapy,
      including bicalutamide monotherapy, may cause less bone loss than ADT.

PMID- 12231058
TI  - Secondary hormonal therapies in the treatment of prostate cancer.
AB  - Patients with androgen-independent prostate cancer demonstrate progression of
      disease, despite chemical or surgical castration, and have a poor prognosis.
      Cancer progression may be manifest as an asymptomatic increase in serum prostate
      specific antigen (PSA) or may be accompanied by symptomatic and/or radiographic
      evidence of tumor growth. Observation remains a reasonable choice for
      asymptomatic patients. However, many patients remain anxious about withholding
      further treatment and, although studies have not demonstrated a survival benefit
      with second-line hormonal therapy, it may be appropriate to consider these
      therapies. In patients who have radiographic and/or symptomatic progression, the
      use of second-line hormonal therapy is more easily justified. Treatment options
      include: (1) secondary use of antiandrogens (eg, high-dose bicalutamide), (2)
      therapies targeted against adrenal steroid synthesis (eg, ketoconazole,
      aminoglutethimide, and corticosteroids), and (3) estrogenic therapies (eg,
      diethylstilbestrol). Symptomatic improvement and PSA-level decreases of > or =50%
      have been reported in approximately 20% to 80% of patients with androgen
      independent prostate cancer who receive such second-line hormone therapies, with
      a typical response duration of 2 to 6 months. Toxicity is generally mild for
      these oral therapies, although serious side effects, including adrenal
      insufficiency, liver toxicity, and thrombosis, may occur. In conclusion,
      secondary hormonal therapies have a significant role in the treatment of patients
      with androgen-independent prostate cancer. Further research is needed to
      understand their optimal use.

PMID- 12231060
TI  - Chemotherapy for prostate cancer.
AB  - Androgen deprivation therapy remains the mainstay of therapy for patients with
      advanced prostate cancer and for selected patients with localized prostate
      cancer. Androgen deprivation therapy is the model of target-based therapies in
      this disease. Although it is clear that other target-based therapies need to be
      developed, cytotoxic chemotherapy is emerging as an effective form of treatment
      for men with prostate cancer. The early studies combining mitoxantrone plus a
      corticosteroid demonstrated that chemotherapy could be given to men with
      symptomatic hormone-refractory prostate cancer with minimal toxicity, and
      significant palliation could be provided. Since then, it has been recognized that
      estramustine, when combined with a variety of microtubular inhibitors, is very
      active in hormone-refractory prostate cancer. Doublets combining estramustine
      plus a taxane seem to be the most active. Although it appears that estramustine
      may add some activity to taxanes, the mechanism of its activity is uncertain, and
      its overall value is similarly questioned, particularly in light of its
      significant toxicity. Regimens that omit estramustine are being explored (ie,
      either taxane alone or taxane plus biologic agents). In addition, triplet therapy
      (combining estramustine plus a taxane plus a third drug, such as carboplatin or
      etoposide) is being explored. Finally, the utility of chemotherapy is beginning
      to be explored in the context of earlier disease in the neoadjuvant, adjuvant, or
      serologically relapsing group of patients. Data from these studies are just
      beginning to be gathered.

PMID- 12231062
TI  - Endpoints in prostate cancer clinical trials.
AB  - Prostate cancer is an extraordinarily heterogeneous disease with a variety of
      prognostic factors influential in determining ultimate patient outcomes. However,
      the vast majority of men harboring pathologic evidence of prostate cancer are not
      clinically diagnosed with this disease. Selected patients, particularly those
      with low clinical stage and low Gleason scores, may have extremely prolonged time
      until disease progression and cancer-specific death. Because of the potential for
      a prolonged natural history, factors, such as age and comorbidities, are often
      critical in evaluating clinical trial outcomes. Patients with more aggressive
      disease (higher clinical stage or Gleason score) have less prolonged natural
      histories. Careful examination of inclusion and exclusion criteria and the
      presence of clinical or pathologic staging are necessary for proper
      interpretation of clinical trials. Although surrogate endpoints, such as prostate
      specific antigen and pathologic state, are commonly used to assess the
      effectiveness of therapeutic interventions, the relations between these
      surrogates and more relevant clinical endpoints have not always been well
      defined. Although certain endpoints are generalizable (overall survival and
      cancer-specific survival), clinical stage and treatments dictate the
      appropriateness of many other clinical trial endpoints. Both disease-related and
      treatment-related endpoints are important, given the propensity for various
      interventions to alter quality of life. Prospective randomized trials with
      adequate follow-up time and the assessment of clinically meaningful endpoints
      will offer the best opportunity to evaluate the effectiveness of various
      interventions used in this disease.

PMID- 12231064
TI  - Novel trial designs: which agents and how do we test them?
AB  - Over the last decade, an increasing number of novel therapies have been tested in
      prostate cancer. Although each agent has potential to affect the natural history
      of the disease, how we should proceed, select, and test these agents to show a
      clinical benefit remains a dilemma. Because prostate cancer is a heterogeneous
      disease, an understanding of the disease states is required to screen and test
      novel agents. Only with the appropriate selection of disease state, trial design,
      and endpoints will we be able to select the most promising regimens to move
      forward.

PMID- 12231066
TI  - Receptor tyrosine kinases as rational targets for prostate cancer treatment:
      platelet-derived growth factor receptor and imatinib mesylate.
AB  - Over the past 15 years, numerous signal transduction pathways have been
      elucidated whose dysregulation may play an important role in the growth and
      survival of cancer cells. The success of imatinib mesylate (Gleevec; Novartis
      Pharmaceuticals, East Hanover, NJ), a small molecule that inhibits the activation
      of the BCR-Abl oncogene in the treatment of chronic myelogenous leukemia, has
      demonstrated how effective targeted strategies can be when properly applied. With
      the hope of selectively targeting other critical components of cancer growth and
      survival while minimizing toxicity to the host, numerous strategies have been
      developed to inhibit receptor tyrosine kinases for various growth factors
      commonly expressed by cancer cells. Success of targeted inhibitors is inherently
      dependent on the proper selection of patients whose tumors are dependent on these
      growth factor pathways. Unfortunately, in prostate cancer, such selection has
      been a difficult-to-impossible task to date. Because of the vast number of
      mutational events, it is difficult to demonstrate that any particular growth
      factor signaling pathway is critical. In addition, because of the type (mostly
      bone only) and nature (usually small foci) of metastases, limited access to tumor
      tissue in the advanced cancer population has hampered attempts to characterize
      patients by their molecular features or phenotype. This article will focus on
      defining alternative criteria for a rational drug target and novel study designs
      for testing these agents in prostate cancer. In particular, the neoadjuvant
      setting represents a unique opportunity for new drug development in prostate
      cancer. An example of a neoadjuvant study testing, imatinib mesylate, is
      presented to display the advantages and limitations of this study design.

PMID- 12231068
TI  - Vitamin D receptor: a potential target for intervention.
AB  - Epidemiologic data suggest that low exposure to vitamin D or 1alpha,25
      dihydroxycholecalciferol (calcitriol) increases the risk of prostate cancer.
      Calcitriol, a central factor in bone and mineral metabolism, is also a potent
      antiproliferative agent in a wide variety of malignant cell types. We have
      demonstrated that calcitriol has significant antitumor activity in vitro and in
      vivo in prostate and squamous cell carcinoma model systems. Calcitriol, in these
      models, induces a significant G0/G1 arrest and modulates p21(Waf1/Cip1) and
      p27(Kip1), the cyclin-dependent kinase inhibitors. Calcitriol induces poly
      (adenosine diphosphate-ribose) polymerase cleavage, increases bax/bcl-2 ratio,
      reduces levels of phosphorylated mitogen-activated protein kinases (P-MAPKs; also
      known as extracellular signal-related kinase [ERK] 1/2) and phosphorylated Akt,
      induces caspase-dependent mitogen-activated protein kinase kinase (MEK) cleavage
      and upregulation of MEK kinase-1, all potential markers of the apoptotic pathway.
      We also have demonstrated that dexamethasone (dex) potentiates the antitumor
      effect of calcitriol through effects on the vitamin D receptor and decreases
      calcitriol-induced hypercalcemia. We initiated phase 1 and phase 2 trials of
      calcitriol, either alone or in combination with carboplatin, paclitaxel, or dex.
      Data from these studies indicate that high-dose calcitriol is feasible on an
      intermittent schedule, the maximum tolerated dose (MTD) is unclear, and dex or
      paclitaxel appear to ameliorate hypercalcemia. Studies continue to define the MTD
      of calcitriol on this intermittent schedule, either alone or with other agents,
      and to evaluate the mechanisms of calcitriol effects in prostate cancer models.

PMID- 12231070
TI  - Androgen receptor as a target in androgen-independent prostate cancer.
AB  - Prostate cancer is dependent on androgen stimulation mediated by the androgen
      receptor (AR), a member of the steroid hormone receptor family of ligand
      dependent nuclear receptors. Most patients respond to standard androgen ablation
      therapies, but virtually all patients eventually relapse with disease that has
      been termed hormone-refractory or androgen-independent disease. Efforts to use AR
      antagonists, such as flutamide or bicalutamide, to enhance responses to primary
      androgen ablation therapy or to treat androgen-independent prostate cancer have
      been disappointing, which has diminished enthusiasm for more aggressive or
      alternative methods to block AR function. However, many lines of evidence
      indicate that AR function contributes to tumor cell survival after androgen
      ablation and to growth of androgen-independent prostate cancer. This article
      outlines a number of mechanisms that may contribute to AR activity in androgen
      independent prostate cancer, including AR amplification, AR mutation, altered
      expression of AR coactivator and corepressor proteins, and activation of other
      pathways that can enhance AR function. Understanding the mechanisms responsible
      for AR function in androgen-independent prostate cancer should allow the more
      rational development of antagonists that can enhance the efficacy of androgen
      ablation therapies.

PMID- 12231073
TI  - Insulin resistance as the core defect in type 2 diabetes mellitus.
AB  - Insulin resistance is a major contributor to the pathogenesis of type 2 diabetes
      and plays a key role in associated metabolic abnormalities, such as dyslipidemia
      and hypertension. Obesity, especially visceral adiposity, is negatively
      correlated with insulin sensitivity. The release of free fatty acids from
      adipocytes can block insulin-signaling pathways and lead to insulin resistance.
      In addition, recently identified adipocyte-specific chemical messengers, the
      adipocytokines, such as tumor necrosis factor-alpha, adiponectin, and resistin,
      appear to modulate the underlying insulin resistance. When insulin resistance is
      combined with beta-cell defects in glucose-stimulated insulin secretion, impaired
      glucose tolerance, hyperglycemia, or type 2 diabetes can result. The
      thiazolidinediones are potent peroxisome proliferator-activated receptor-gamma
      agonists and directly improve insulin resistance and glycemic control in patients
      with type 2 diabetes. Increasing evidence supports the early use of
      thiazolidinediones for preventing, delaying, or treating diabetes by improving
      insulin sensitivity and beta-cell insulin secretion.

PMID- 12231074
TI  - Pathogenesis of skeletal muscle insulin resistance in type 2 diabetes mellitus.
AB  - Insulin resistance is a principal feature of type 2 diabetes and precedes the
      clinical development of the disease by 10 to 20 years. Insulin resistance is
      caused by the decreased ability of peripheral target tissues (especially muscle)
      to respond properly to normal circulating concentrations of insulin. Defects in
      muscle glycogen synthesis play a significant role in insulin resistance, and 3
      potentially rate-controlling steps in muscle glucose metabolism have been
      implicated in its pathogenesis: glycogen synthase, hexokinase, and GLUT4 (the
      major insulin-stimulated glucose transporter). Results from recent studies using
      nuclear magnetic resonance (NMR) spectroscopy implicate intracellular defects in
      glucose transport as the rate-controlling step for insulin-mediated glucose
      uptake in muscle. These alterations in glucose transport activity are likely the
      result of dysregulation of intramyocellular fatty acid metabolism, whereby fatty
      acids cause insulin resistance by activation of a serine kinase cascade, leading
      to decreased insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine
      phosphorylation and decreased IRS-1-associated phosphatidylinositol 3-kinase
      activity, a required step in insulin-stimulated glucose transport into muscle.
      The thiazolidinedione class of antidiabetic agents directly targets insulin
      resistance in skeletal muscle by improving glucose transport activity and insulin
      stimulated muscle glycogen synthesis. Although the precise mechanism of action is
      not known, recent NMR studies support the hypothesis that these agents improve
      insulin action in skeletal muscle and liver by promoting a redistribution of fat
      out of these tissues and into peripheral adipocytes.

PMID- 12231075
TI  - Current concepts in insulin resistance, type 2 diabetes mellitus, and the
      metabolic syndrome.
AB  - A clustering of risk factors, including elevated triglycerides, decreased high
      density lipoprotein cholesterol, hyperinsulinemia, and hypertension often are
      observed in patients who are insulin resistant. Insulin resistance has been found
      to play a critical role in the development of cardiovascular disease,
      particularly in patients with type 2 diabetes. Patients with insulin resistance
      have an increase in small, dense low-density lipoprotein (LDL) cholesterol, which
      is more atherogenic than large, buoyant LDL cholesterol. In the context of
      insulin resistance, insulin has reduced effects on the phosphatidylinositol 3
      kinase (PI3K) pathway, whereas mitogen-activated protein kinase activity is
      maintained. The result is an exaggeration of the mitogenic actions of insulin
      leading to vascular smooth muscle proliferation and elevated plasminogen
      activator inhibitor (PAI)-1. Notably, nitric oxide-mediated vasodilation also is
      impaired, further contributing to atherogenicity. In addition, hyperinsulinemia
      further contributes to cardiovascular risk by promoting thrombosis. Patients who
      are insulin resistant have decreased fibrinolysis, as indicated by increased
      levels of PAI-1. Studies have shown that enhancing insulin sensitivity with
      insulin sensitizers, such as thiazolidinediones, may improve insulin resistance
      and limit the development of adverse cardiovascular consequences.

PMID- 12231076
TI  - A rational approach to pathogenesis and treatment of type 2 diabetes mellitus,
      insulin resistance, inflammation, and atherosclerosis.
AB  - Type 2 diabetes and obesity are major risk factors for the development of
      coronary artery disease (CAD) and premature atherosclerosis. Both conditions are
      associated with insulin resistance, oxidative stress, and inflammation.
      Inflammatory mediators, including plasma interleukin 6, tumor necrosis factor
      alpha, and tumor necrosis factor R are elevated in these individuals. The
      elevations of inflammatory mediators may contribute to the pathogenesis of
      atherosclerosis, because atherosclerosis is an inflammation of the arterial wall.
      There is evidence that the thiazolidinedione (TZD) class of drugs may alleviate
      some of the adverse atherosclerotic effects common in patients with type 2
      diabetes. Considerable recent data suggest that the TZDs possess anti
      inflammatory properties and exert an effect on the atherogenic process, including
      effects on endothelial function, monocyte/macrophage function, lipid
      abnormalities, smooth muscle cell migration, and fibrinolysis, all functions that
      are abnormal in the presence of insulin resistance. These actions of TZDs are
      consistent with the recently described anti-inflammatory effects of insulin. The
      use of TZDs as potent anti-inflammatory agents in patients with type 2 diabetes
      is an approach that would normalize glucose levels, as well as potentially
      alleviate the long-term risk of atherosclerosis.

PMID- 12231077
TI  - Rationale for and role of thiazolidinediones in type 2 diabetes mellitus.
AB  - Several classes of antihyperglycemic agents are available for the treatment of
      patients with type 2 diabetes. These agents, including thiazolidinediones,
      biguanides, insulin secretagogues, alpha-glucosidase inhibitors, and insulin,
      offer differing mechanisms of actions and can be used either alone or in
      combination. The thiazolidinediones are a newer class of oral antidiabetic agents
      that improve glycemic control and may preserve beta-cell function. Clinical trial
      data suggest that patients with type 2 diabetes experience progressive
      deterioration of beta-cell function. By decreasing insulin resistance,
      thiazolidinediones may preserve beta-cell function, and patients may experience
      prolonged glycemic control. The thiazolidinediones also exert beneficial effects
      on dyslipidemia, endothelial function, coagulation, and blood pressure. By
      improving these components of the metabolic syndrome, thiazolidinediones may
      reduce the incidence of both microvascular and macrovascular complications. This
      article provides an overview of the role of thiazolidinediones in the treatment
      of type 2 diabetes.

PMID- 12231078
TI  - Reappraisal of the pharmacologic approach to treatment of type 2 diabetes
      mellitus.
AB  - Nearly 16 million adults in the United States have diabetes mellitus, and the
      incidence of type 2 diabetes, the most prevalent form of diabetes, has steadily
      increased during the past decade. Patients with diabetes are at increased risk
      for microvascular and macrovascular complications and experience significant
      morbidity and mortality. Diabetes is the leading cause of blindness, end-stage
      renal disease, and nontraumatic amputations in adults. Because diabetes is a
      progressive disorder, the importance of early and appropriate treatment cannot be
      overemphasized. Present therapeutic strategies for the management of type 2
      diabetes are adequate but are not maximally effective. Clearly, reappraisal of
      the pharmacologic approach to the optimal management of patients with type 2
      diabetes is needed. A number of oral hypoglycemic agents, including
      thiazolidinediones, biguanides, sulfonylureas, and alpha-glucosidase inhibitors,
      may be used to normalize glucose levels in patients with type 2 diabetes. Because
      insulin resistance is an underlying pathologic defect in patients with type 2
      diabetes, agents that increase insulin sensitivity should be used early in the
      course of therapy. By using a multifaceted approach to target insulin resistance,
      many patients with type 2 diabetes may achieve normoglycemia and improved long
      term outcomes.

PMID- 12231079
TI  - Debulking and stenting versus debulking only of coronary artery disease in
      patients treated with cilostazol (final results of ESPRIT).
AB  - Stenting inhibits vascular constrictive remodeling after directional coronary
      atherectomy (DCA). Cilostazol has been reported to control neointimal
      proliferation after stenting. This study's aim was to examine the effect of
      debulking and stenting with antirestenotic medication on restenosis. After
      optimal DCA, 117 lesions were randomly assigned to either the DCA with stent (DCA
      stent) (58 lesions) group or the DCA only (59 lesions) group. Multilink stents
      were implanted in the DCA-stent group. Cilostazol (200 mg/day) without aspirin
      was administered to both groups for 6 months. Ticlopidine (200 mg/day) was given
      to the DCA-stent group for 1 month. Serial quantitative angiography and
      intravascular ultrasound (IVUS) were performed at the time of the procedure and
      at 6-month follow-up. The primary end point was 6-month angiographic restenosis.
      Clinical event rates at 1 year were also assessed. Baseline characteristics were
      similar. All procedures were successful. No adverse effects to cilostazol were
      observed. Postprocedural lumen diameter was significantly larger (3.27 vs 2.92
      mm; p <0.0001) in the DCA-stent group. However, the follow-up lumen diameter was
      not significantly different (2.53 vs 2.41 mm, DCA-stent vs DCA). IVUS revealed
      that intimal proliferation was significantly larger in the DCA-stent group (4.2
      vs 1.5 mm(2); p <0.0001), which accounted for the similar follow-up lumen area
      (6.5 vs 7.1 mm(2)). The restenosis rate was low in both groups (5.4% vs 8.9%),
      and the difference was not significant. Clinical event rates at 1 year were also
      not significantly different. These results suggest that optimal lesion debulking
      by DCA does not always need adjunctive stenting if cilostazol is administered.

PMID- 12231080
TI  - Prevalence of coronary occlusion and outcome of an immediate invasive strategy in
      suspected acute myocardial infarction with and without ST-segment elevation.
AB  - The prevalence of flow-limiting coronary lesions at the time of presentation in
      patients with non-ST-segment elevation myocardial infarction (NSTEMI) is unknown.
      Because rational reperfusion strategies depend on early, accurate identification
      of coronary flow limitation, we performed coronary angiography at the time of
      presentation of patients with suspected NSTEMI. We also evaluated outcomes of an
      immediate interventional strategy. A comparison is made with suspected ST-segment
      elevation myocardial infarction (STEMI). Unselected consecutive patients with
      suspected STEMI or NSTEMI were enrolled in a prospective observational cohort
      study. Suspected STEMI was defined according to standard criteria. Suspected
      NSTEMI was identified by clinical evaluation of symptoms, electrocardiographic
      changes, persistence of ischemic pain for >20 minutes despite treatment, and/or
      hemodynamic instability. Biochemical evidence of myocardial necrosis on
      presentation was not mandatory. An immediate, around-the-clock invasive strategy
      was applied. Significant coronary lesions were found in 94% of 279 patients with
      suspected STEMI and in 90% of 125 patients with suspected NSTEMI, and coronary
      occlusion or flow limitation was present in 75% and 63% of patients,
      respectively. Immediate percutaneous coronary intervention was performed in 74%
      and 60%, respectively, and an additional 13% and 18%, respectively, had coronary
      artery bypass surgery during the index admission. In-hospital mortalities in the
      patients with suspected STEMI and NSTEMI were 4.7% and 5.6%, respectively. An
      additional 1.9% and 2.5% died at 6 months. The prevalence of coronary flow
      limitation in clinically suspected NSTEMI is almost as high as in suspected
      STEMI. Short- and long-term outcomes of an immediate invasive strategy are
      similar for the 2 conditions.

PMID- 12231081
TI  - Comparison of one-year outcomes following coronary artery stenting in diabetic
      versus nondiabetic patients (from the Enhanced Suppression of the Platelet
      IIb/IIIa Receptor With Integrilin Therapy [ESPRIT] Trial).
AB  - For patients undergoing nonurgent coronary stent implantation, blockade of the
      glycoprotein IIb/IIIa receptor with eptifibatide reduces the incidence of
      ischemic complications. We evaluated the interaction of eptifibatide with
      diabetes in patients who underwent this procedure by analyzing the 1-year
      outcomes of those enrolled in the Enhanced Suppression of the Platelet IIb/IIIa
      Receptor with Integrilin Therapy (ESPRIT) trial (466 diabetic and 1,595
      nondiabetic patients). At 1 year, the composite end point of death, myocardial
      infarction (MI), or target vessel revascuarlization (TVR) was higher in diabetic
      patients (24.5% vs 18.4%; p = 0.008). At 1 year, eptifibatide had a similar
      effect on the composite end point of death, MI, or TVR in diabetic (hazards ratio
      [HR] 0.71, 95% confidence interval [CI] 0.49 to 1.04) and nondiabetic patients
      (HR 0.80, 95% CI 0.63 to 0.99). A similar treatment effect was also seen on death
      or MI in both groups. The 1-year mortality rate for diabetic patients assigned to
      placebo was 3.5% versus 1.3% for patients receiving eptifibatide (HR 0.37, 95% CI
      0.10 to 1.41); the latter rate was similar to the mortality rate of 1.4% for
      nondiabetic patients in the eptifibatide group. However, eptifibatide did not
      have a significant effect on TVR in diabetic patients (HR 0.90, 95% CI 0.57 to
      1.41). Our data suggest that treatment with eptifibatide is associated with a
      similar relative reduction in adverse ischemic complications in diabetic and
      nondiabetic patients undergoing coronary stent implantation. There is no evidence
      of a statistical interaction in the treatment effect of eptifibatide between
      patients with and without diabetes.

PMID- 12231082
TI  - Relation of plasma total homocysteine to cardiovascular mortality in a French
      population.
AB  - Although there is considerable epidemiologic evidence for a relation between
      plasma homocysteine (HCY) and cardiovascular (CV) disease, the role of HCY as a
      causal CV risk factor remains controversial, mainly because of the
      intercorrelation between HCY and other CV risk factors. The goal of the present
      nested case-control prospective study is to determine the multiadjusted relation
      between HCY and CV mortality in a large and low CV risk population after a mean
      follow-up of 14 years. In 1980 and 1981, plasma was saved from 5,000 patients who
      underwent a systematic health checkup, including clinical and biologic
      examinations. In 1999, HCY concentration was measured in 110 subjects who died of
      CV disease (cases) and in 154 randomly matched survivors (control subjects).
      Statistical analysis was adjusted for CV risk factors. Based on Cox analyses, 3
      factors emerged as independent predictors of CV mortality: C-reactive protein,
      systolic blood pressure, and HCY. The adjusted hazard ratio for CV mortality was
      1.22 (95% confidence interval 1.04 to 1.41) per 1 SD (3.9 micromol/L) increment
      of HCY. Thus, HCY is an independent risk predictor for CV mortality. Because of
      extensive adjustment procedures, the present study provides additional
      epidemiologic evidence for a causal relation between HCY and CV disease.

PMID- 12231083
TI  - Effects of furosemide versus captopril on postprandial and orthostatic blood
      pressure and on cerebral oxygenation in patients > or = 70 years of age with
      heart failure.
AB  - Elderly patients with heart failure are at risk of postprandial hypotension
      (PPH), orthostatic hypotension (OH), and concomitant cerebral oxygenation changes
      because of altered cardiovascular balance and the use of cardiovascular
      medications, such as furosemide and captopril. In 24 patients with heart failure
      (New York Heart Association class II to III, in stable condition, and receiving
      cardiovascular medication [aged 70 to 83 years]), blood pressure (BP) was
      measured by Finapres, and cortical concentrations of oxyhemoglobin and
      deoxyhemoglobin were measured using near-infrared spectroscopy during standing
      and after a 292-kcal carbohydrate meal. Tests were performed before and during
      therapy with furosemide 40 mg once daily (n = 11) or captopril 6.25 and 12.5 mg
      twice daily (n = 13) in a double-blind randomized trial. Before treatment, 13 of
      24 patients had PPH, and 2 of 24 patients had OH. The first dose of furosemide
      significantly decreased postprandial systolic BP (p <0.05) and postprandial
      frontal cortical oxygenation (p <0.05), whereas the first dose of captopril did
      not. Furosemide and captopril did not significantly affect postprandial or
      orthostatic BP or cortical oxygenation after 2 weeks of treatment. Thus, PPH is a
      common phenomenon in elderly patients with heart failure, whereas OH is not. The
      first dose of furosemide 40 mg decreased postprandial systolic BP and frontal
      cortical oxygenation, in contrast with the first dose of captopril 6.25 mg and 2
      week treatment with furosemide 40 mg once daily or captopril 12.5 mg twice daily.
      These findings indicate that initiating furosemide treatment worsens PPH, and
      furosemide is less safe in elderly patients with heart failure.

PMID- 12231084
TI  - Comparison of left ventricular geometry and left atrial size and function in
      patients with aortic stenosis versus those with pure aortic regurgitation.
AB  - Chronic aortic valve disease can result in distinct adaptive left ventricular
      (LV) geometric patterns, which has different effects on LV function and left
      atrial (LA) performance. In this study we assessed the effect of LV geometry on
      LA size and function, and we verified the relation between LA size and LV mass in
      patients with distinct LV overload subsets. We analyzed 183 patients with aortic
      valve disease who underwent a complete echocardiographic evaluation. Based on the
      type of valvular dysfunction, patients were classified into 2 groups: 141
      patients with aortic stenosis (group AS) and 42 patients with pure aortic
      regurgitation (group AR). Each of these 2 groups were then divided into those
      with a concentric LV pattern and those with an eccentric pattern. Both LA size
      and LA ejection force were significantly greater in group AS than group AR,
      particularly in patients with a concentric LV pattern. The degree of LA
      enlargement depended on LV mass in the patients with a concentric LV pattern
      (group AS r = 0.61, p <0.00001; group AR r = 0.38, p = 0.04). In contrast, no
      relation was found between LA size and LV mass in the patients with an eccentric
      pattern, independently of the type of valve dysfunction. Our results indicate
      that the influence of LV geometry on LA size and function in patients with aortic
      valve disease is relevant. A concentric LV pattern is associated with greater LA
      size and higher ejection than an eccentric pattern, suggesting that chronic LV
      pressure overload more than volume overload has a greater effect on stimulating
      increases in LA performance. The degree of LA enlargement depends on LV mass in
      patients with a concentric LV pattern, whereas it was unpredictable in those with
      an eccentric LV pattern.

PMID- 12231085
TI  - Prospective validation of an echocardiographic index for determining the severity
      of chronic mitral regurgitation.
AB  - The aim of this study is to prospectively validate a recently reported
      semiquantitative index of mitral regurgitation (MR) severity. MR is a common
      echocardiographic finding with no single reference standard to evaluate its
      severity. We recently developed and retrospectively tested a semiquantitative
      index of MR severity. The MR index is a composite of 6 echocardiographic
      variables: jet penetration, proximal isovelocity surface area, continuous-wave
      Doppler characteristics of the regurgitant jet, pulmonary artery pressure,
      pulmonary venous flow pattern, and left atrial size. Sixty-two consecutive
      patients with varying grades of MR were prospectively studied. Patients were
      divided into 3 groups for comparison: mild MR, moderate MR, and severe MR. Each
      patient was evaluated for the 6 variables, with each variable scored on a 4-point
      scale (0 to 3). The reference standards for MR severity were qualitative
      evaluation by an expert, measurement of the regurgitant fraction (RF), and the
      effective regurgitant orifice area. The MR index increased in proportion to MR
      severity with a significant difference among the 3 groups (F = 84; p <0.0001).
      The MR index also correlated with RF (r = 0.73; p <0.0001) and the effective
      regurgitant orifice area (r = 0.74; p = 0.0001). A MR index > or = 2.2 identified
      13 of 16 patients with severe MR (sensitivity 82%, specificity 98%, positive
      predictive value 93%). No patient with severe MR had a score <2.0 and no patient
      with mild MR had a score >1.67. These results concurred with those obtained in a
      previously published retrospective study. Thus, the MR index is a simple,
      reproducible semiquantitative estimate of MR severity, that is widely applicable
      in routine clinical practice.

PMID- 12231086
TI  - Echocardiographic determinants of mitral early flow propagation velocity.
AB  - Transmitral color Doppler early diastolic flow propagation velocity (Vp) has been
      correlated with the left ventricular (LV) relaxation time constant tau in dilated
      cardiomyopathy and ischemic heart disease. The aim of this study was to
      investigate the independent influence of LV systolic function and geometry, and
      of LV relaxation, on Vp in an unselected outpatient population. We studied 30
      normal subjects and 130 patients (hypertensive LV hypertrophy, aortic valve
      stenosis or prosthesis, hypertrophic cardiomyopathy, coronary artery disease,
      dilated cardiomyopathy, aortic or mitral valve regurgitation). In all, we
      noninvasively measured LV geometry, mass, systolic function, wall motion
      dyssynergy, and diastolic function (abnormal relaxation or restrictive LV Doppler
      filling patterns). The Vp was similar in normal subjects and in patients (51 +/-
      14 vs 53 +/- 25 cm/s). In normal subjects, the determinants of Vp at multiple
      regression analysis were isovolumic relaxation time, 2-dimensional cardiac index,
      and mitral E-wave velocity-time integral. In all, the main determinants were LV
      ejection fraction, percent of segmental wall dyssynergy, and isovolumic
      relaxation time and age. The Vp was highest in hypertrophic (75 +/- 25 cm/s, p
      <0.05 vs normal subjects) and lowest in dilated (35 +/- 13 cm/s, p = NS)
      cardiomyopathy. During multivariate analysis of variance, percent of wall
      dyssynergy (but not diffuse LV hypokinesia) independently reduced Vp (p = 0.02).
      The latter was not influenced by the LV filling pattern. Thus, in an unselected
      clinical population, prolonged relaxation per se does not influence Vp if LV
      systolic dysfunction and/or wall dyssynergy is absent-the latter factors are
      important independent determinants of Vp, which is determined by multiple
      factors.

PMID- 12231087
TI  - The Personal Professor: continuing medical education meets the new media.

PMID- 12231088
TI  - Seeking the optimal aspirin dose in acute coronary syndromes.

PMID- 12231089
TI  - Amplified benefit of clopidogrel versus aspirin in patients with diabetes
      mellitus.

PMID- 12231090
TI  - Abciximab survival advantage following percutaneous coronary intervention is
      predicted by clinical risk profile.

PMID- 12231091
TI  - Efficacy and safety of multivessel percutaneous revascularization and tirofiban
      therapy in patients with acute coronary syndromes.

PMID- 12231092
TI  - Elevations of cardiac troponin I are associated with increased short-term
      mortality in noncardiac critically ill emergency department patients.

PMID- 12231093
TI  - Remodeling pattern within diseased coronary segments as evidenced by
      intravascular ultrasound.

PMID- 12231094
TI  - Intravascular ultrasonic evaluation of the magnitude of stent expansion and the
      mechanisms of lumen enlargement after direct stenting and after conventional
      stenting with balloon predilatation.

PMID- 12231095
TI  - Comparison of courses of patients with acute myocardial infarction with chest
      pain appearing during exertion versus those with chest pain not occurring during
      exertion.

PMID- 12231096
TI  - Benefits of cardiac rehabilitation in the ninth decade of life in patients with
      coronary heart disease.

PMID- 12231097
TI  - Direct association between high-density lipoprotein cholesterol and endothelial
      function in hyperlipemia.

PMID- 12231099
TI  - Nonarrhythmic syncope documented by an implantable loop recorder (an ISSUE
      substudy).

PMID- 12231098
TI  - Antibodies against oxidized low-density lipoprotein in normolipidemic smokers.

PMID- 12231100
TI  - Effectiveness and safety of low-energy internal cardioversion of long-standing
      atrial fibrillation after unsuccessful external cardioversion.

PMID- 12231101
TI  - Prevalence of intra-atrial thrombi in atrial fibrillation patients with
      subtherapeutic international normalized ratios while taking conventional
      anticoagulation.

PMID- 12231102
TI  - Estimation of glomerular filtration rate to prevent life-threatening hyperkalemia
      due to combined therapy with spironolactone and angiotensin-converting enzyme
      inhibition or angiotensin receptor blockade.

PMID- 12231103
TI  - Hyperkalemia in congestive heart failure patients aged 63 to 85 years with
      subclinical renal disease.

PMID- 12231104
TI  - Relation of the total ejection isovolume index to symptoms in aortic stenosis.

PMID- 12231105
TI  - Feasibility and usefulness of right ventricular ultrasonic tissue
      characterization with integrated backscatter in patients with unsuccessfully
      operatively "repaired" tetralogy of Fallot.

PMID- 12231106
TI  - Relation of mesenteric vascular resistance after Fontan operation and protein
      losing enteropathy.

PMID- 12231107
TI  - Acute peripheral arterial ischemia and suspected aortic dissection: usefulness of
      transesophageal echocardiography in differential diagnosis with aortic
      thrombosis.

PMID- 12231108
TI  - Effect of sildenafil on the acute pulmonary vasodilator response to inhaled
      nitric oxide in adults with primary pulmonary hypertension.

PMID- 12231109
TI  - Lifestyle changes in New Yorkers after September 11, 2001 (data from the Post
      Disaster Heart Attack Prevention Program).

PMID- 12231110
TI  - Getting more people on statins.

PMID- 12231111
TI  - Prostanoids do not affect endothelium-dependent vasodilation in healthy humans.

PMID- 12231112
TI  - Long-term results of percutaneous balloon mitral valvuloplasty with the Inoue
      balloon catheter in elderly patients.

PMID- 12231113
TI  - Practice patterns related to the Adult Treatment Panel III guidelines in primary
      care.

PMID- 12231114
TI  - Transesophageal echocardiography in patients with recent stroke and normal
      carotid arteries.

PMID- 12231116
TI  - The estrogen receptor alpha gene determines serum androstenedione levels in
      postmenopausal women.
AB  - Estrogen receptors (ER) are expressed not only in the reproductive system and
      ovaries but also in some other tissues, including the adrenal gland. The purpose
      of this study was to assess the association between the estrogen receptor (ER)
      alpha gene polymorphisms XbaI and PvuII and circulating levels of
      androstenedione, a precursor of sex-steroids synthetized in the ovary and
      adrenal. After adjustment for years since menopause, body mass, and
      dehydroepiandrosterone (DHEA) levels, a highly significant relationship was
      demonstrated between androstenedione and XbaI or PvuII polymorphisms, the highest
      levels of the hormone being found in the xx and pp genotypes (P<0.05 as compared
      to XX or PP, ANCOVA followed by least significant difference (LSD) multiple
      comparisons). This suggests that the ER genotype may determine the function of
      the sex-steroid system not only at the receptor level but also at the level of
      hormone synthesis. The pathogenetic role of this association in diseases related
      to menopause, such as osteoporosis, remains to be determined.

PMID- 12231117
TI  - Inhibition of steryl sulfatase activity in LNCaP human prostate cancer cells.
AB  - The enzyme steryl sulfatase may help support the growth of hormone-dependent
      tumors, including prostate cancers, by facilitating the conversion of circulating
      precursor steroids to active hormones. We sought to determine the presence of
      steryl sulfatase activity in the androgen-dependent human prostate cancer cell
      line LNCaP, and to determine if this activity was inhibited by known steryl
      sulfatase inhibitors. Intact LNCaP cultures had steryl sulfatase activity, as
      determined by conversion of [3H]estrone sulfate (E(1)S) to unconjugated steroids.
      The level of steryl sulfatase activity was relatively low (4.6 pmol/18 h/million
      cells) compared to MDA-MB-231 breast cancer cells (284.0 pmol/18 h/million
      cells). The observed activity in both cell lines was blocked by addition of 1
      microM estrone sulfamate (EMATE), an active-site-directed, steroidal inhibitor of
      steryl sulfatase. Steryl sulfatase activity was also inhibited by Danazol, and by
      (p-O-sulfamoyl)-tetradecanoyl tyramine (C2-14), a non-steroidal inhibitor.
      Microsomes prepared from LNCaP cultures also showed steryl sulfatase activity, as
      determined by hydrolysis of [3H]E(1)S and [3H]dehydroepiandrosterone sulfate
      (DHEAS) to unconjugated forms. LNCaP and MDA-MB-231 microsomes both hydrolyzed
      E(1)S about two times faster than DHEAS. Hydrolysis of E(1)S in LNCaP and MDA-MB
      231 microsomes was blocked by steryl sulfatase inhibitors with the following
      relative potencies: EMATE>C2-14>Danazol. These data demonstrate that LNCaP
      prostate cancer cells contain a steryl sulfatase with properties similar to that
      found in human breast cancer cells, and that the activity of this enzyme can be
      blocked by known steryl sulfatase inhibitors. Steryl sulfatase inhibitors may be
      useful as an adjuvant to androgen deprivation therapy for prostate cancer.

PMID- 12231118
TI  - A monoclonal antibody-based enzyme-linked immunosorbent assay of glycolithocholic
      acid sulfate in human urine for liver function test.
AB  - Urinary levels of sulfated metabolites of lithocholic acid (LCA) are expected to
      be a useful index of liver function. Thus, a sensitive, specific, and feasible
      enzyme-linked immunosorbent assay (ELISA) of these sulfated LCA metabolites (LCA
      Suls) should be established. A newly generated monoclonal antibody specific to
      glycolithocholic acid sulfate (glycine-amidated LCA-Sul (GLCA-Sul)) was
      immobilized on microtiter plates via a second antibody. A urine specimen and an
      alkaline phosphatase-labeled antigen were added to the plate, which was then
      incubated at room temperature for 3h. After this competitive reaction, bound
      enzyme activity was measured colorimetrically using p-nitrophenyl phosphate as a
      substrate. The detection limit for GLCA-Sul was 0.4 pg/assay. Nonamidated LCA-Sul
      and taurine-conjugated LCA-Sul showed 40 and 11% cross-reactivities,
      respectively, while 3-sulfates of cholic acid (CA; 0.02%), chenodeoxycholic acid
      (CDCA; 0.63%), and deoxycholic acid (DCA; 2.2%) exhibited very low cross
      reactivities. Applicability of the ELISA system to clinical samples was well
      validated by parallelism, recovery test, and intra/inter-assay variance.
      Enzymatic deconjugation with bile acids sulfatase resulted in dramatically
      decreased urinary levels, supporting the specificity of the ELISA toward GLCA
      Sul. The mean GLCA-Sul levels in early morning urine from healthy volunteers were
      314 ng/mg Ucre (males: n=16) and 507 ng/mg Ucre (females: n=9). Patients with
      liver diseases, including chronic hepatitis (CH) and liver cirrhosis (LC)
      exhibited significantly higher values (mean 5222 ng/mg Ucre: n=21). The present
      'monoclonal ELISA' is predicted to be useful as a novel noninvasive diagnostic
      tool for liver function and hepatobiliary diseases.

PMID- 12231119
TI  - Synthesis, structure and catechol-oxidase activity of copper(II) complexes of 17
      hydroxy-16-(N-3-oxo-prop-1-enyl)amino steroids.
AB  - Copper is next to iron the most important element in the biological transport,
      storage and in redox reactions of dioxygen. A bioanalogous activation of dioxygen
      with copper complexes is used for catalytical epoxidation, allylic hydroxylation
      and oxidative coupling of aromatic substrates, for example. With stereochemical
      information in form of chiral ligands, enantioselective reactions may be
      possible. Another aspect of interest on copper catalyzed reactions with dioxygen
      is that the exact mechanism and biological function of some enzymes (especially
      catechol oxidase) is yet not fully clear. For studies mimicking the copper
      containing catechol oxidase appropriate chiral steroid ligands with defined
      stereochemistry and conformation have been synthesized. The four diastereomeric
      16,17-aminoalcohols of the 3-methoxy-estra-1,3,5(10)-triene series have been
      condensed with salicylic aldehyde and different beta-ketoenols to the chiral
      ligand types 1-5. These compounds with different steric and electronic properties
      and different arrangements of the neighboring hydroxy and nitrogen functions were
      reacted with copper(II) acetate to copper complexes. The structure of these
      complexes will be discussed. The bioanalogous oxidation of 3,5-di-tbutyl-catechol
      (dtbc) to the corresponding quinone was catalyzed by most of the complexes,
      indicating their ability to activate dioxygen. The trans configurations c and d
      showed an activity one magnitude higher than the cis configurations a and b.
      Comparing compounds with the same diastereomeric configuration, the main
      influence was that of the peripheral R(1-3) substituents at the beta-ketoenaminic
      group which are useful for the fine-tuning of the properties of the copper atoms
      like redox potential and Lewis acidity.

PMID- 12231120
TI  - Determination of 11-deoxycortisol (Reichstein's compound S) in human plasma by
      clinical isotope dilution mass spectrometry using benchtop gas chromatography
      mass selective detection.
AB  - A first assay based on stable isotope dilution/gas chromatography-mass
      spectrometry (ID/GC-MS) has been developed for plasma 11-deoxycortisol
      (Reichstein's compound S), the leading hormonal marker of 11beta-hydroxylase
      deficiency. A suitable internal standard being unavailable, we synthesized
      dideuterated 11-deoxycortisol according to a newly devised synthetic procedure.
      17,21-Dihydroxy-pregna-1,4-diene-3,20-dione underwent selective deuteration using
      Wilkinson's catalyst. Our product [1alpha,2alpha-2H2]11-deoxycortisol was
      obtained in good yield (35.6%) and high isotopic purity (0.1% 2H0, 99.9% 2H2).
      Structural confirmation was done by MS and NMR. Our plasma work up consisted of
      equilibration of plasma with internal standard ([1alpha,2alpha-2H2]11
      deoxycortisol), solid phase extraction with Extrelut NT columns, a clean up step
      using Sephadex LH-20 mini columns and preparation of heptafluorobutyrates as
      derivatives. Quantification was achieved by selected ion monitoring of m/z 465.40
      (analyte) and m/z 467.40 (internal standard). One hundred twenty picograms of 11
      deoxycortisol gave a signal to noise ratio of 10. Calibration plot was linear.
      Spiking experiments showed good accuracy with relative errors <3.0%. Intraassay
      precision CV was 4.78% and interassay precision CV was 4.56%. We succeeded in
      integrating our new analyte into our already existing multisteroid ID/GC-MS
      plasma assay, which now, in its expanded version, is capable of determining all
      major diagnostic steroids of androgen related disorders in a single profile: 11
      deoxycortisol, 17alpha-hydroxyprogesterone, testosterone, 4-androstenedione,
      17alpha-hydroxypregnenolone, dehydroepiandrosterone, androstanediol and 5alpha
      dihydrotestosterone. The diagnostic potential of our multisteroid ID/GC-MS assay,
      the small amounts of plasma (0.5 ml) required, the rapid and convenient sample
      work up, the application of benchtop GC-MS instrumentation, and highest
      specificity offered by mass spectrometric detection prove our assay suitable for
      routine clinical use, especially in pediatric endocrinology.

PMID- 12231121
TI  - Effects of butyltins on human 5alpha-reductase type 1 and type 2 activity.
AB  - Butyltins are widely used biocides and accumulate in the food chain. Tributyltin
      is an imposex-inducing endocrine disrupter in animals. Imposex is characterized
      by the development of additional male sex organs on females. In a previous study,
      we identified tributyltin as an inhibitor of human cytochrom P450 aromatase
      activity. The present work focuses on the impact of butyltins on human androgen
      metabolism. Activation of androgens is mediated by two human 5alpha-reductase
      isoenzymes. 5alpha-Reductase type 1 was completely inhibited by tributyltin
      chloride (IC50=19.9 microM) and dibutyltin dichloride (IC50=32.9 microM), whereas
      5alpha-reductase type 2 was only inhibited by tributyltin chloride (IC50=10.8
      microM). Both isoenzymes were not affected by tetrabutyltin or monobutyltin
      indicating that at least two butyl groups bound to the positively charged Sn are
      required for the interaction of butyltins with the enzymes. Tributyltin inhibited
      5alpha-reductase type 1 competitively whereas an irreversible inhibition was
      evident for the type 2 isoenzyme. In contrast to the distinct effects on 5alpha
      reductases, reductive brain 17beta-hydroxysteroid dehydrogenase activity was not
      inhibited by any butyltin. Insufficient activation of androgens is responsible
      for developmental disorders of the male reproductive system such as hypospadias.
      At pharmacologic levels butyltins might contribute to the onset of developmental
      disorders of the male reproductive system. At present, however, it is unknown
      whether these levels are reached after acute or chronic exposure to butyltins.

PMID- 12231122
TI  - Microbial transformation of hydrocortisone by Acremonium strictum PTCC 5282.
AB  - The ability of a genus of cephalosporium-like fungus isolated from soil,
      Acremonium strictum PTCC 5282, for hydrocortisone biotransformation has been
      investigated. This potential had not been previously examined. The fermentation
      yielded 11beta,17beta-dihydroxyandrost-4-en-3-one, 11beta,17alpha,20beta,21
      tetrahydroxypregn-4-en-3-one and 21-acetoxy-11beta,17alpha,20-trihydroxypregn-4
      en-3-one. Each microbial metabolite was purified and characterized using
      spectroscopic methods.

PMID- 12231123
TI  - Study of natural and artificial corticosteroid phase II metabolites in bovine
      urine using HPLC-MS/MS.
AB  - Corticosteroid compounds are widely used therapeutically for their anti
      inflammatory properties and sometimes as growth promoters in food producing
      animals. In the field of drug residue analysis, knowledge of the main metabolic
      pathways of target analytes improves the efficiency of the corresponding control.
      Thus, phase II metabolism of corticosteroids, for which very little literature is
      available, was investigated in cattle. An LC-MS/MS detection method was developed
      for five commercially available conjugated corticosteroids, permitting direct
      monitoring during the development of their separation on anion exchange SPE. This
      separation method is further applicable to other potential urinary conjugated
      corticosteroids. Because our purpose was not to identify all the existing
      corticosteroid phase II metabolites, but to obtain their total relative
      proportions, enzymatic hydrolysis was optimized and performed on each separated
      fraction (glucuronides and sulfates). Finally, the phase II metabolic profiles of
      natural and artificial corticosteroids in bovine urine were studied and compared.
      LC-MS/MS detection with negative electrospray ionization appeared efficient for
      both glucuronide and sulfate conjugated corticosteroids, and quaternary ammonium
      stationary phase permitted their effective separation. The experimental design
      used for optimization of the enzymatic hydrolysis with a purified Helix pomatia
      preparation demonstrated optimal values for pH 5.2, temperature of 50 degrees C
      and incubation duration of 4h. Results on bovine urine samples collected on two
      animals before and after dexamethasone administration showed important
      differences regarding the proportion of total conjugated forms between endogenous
      cortisol, endogenous tetrahydrocortisol, and exogenous dexamethasone. This
      proportion appeared significantly higher for tetrahydrocortisol (40-65%) than
      cortisol (2-8%) or dexamethasone (4-27%). This innovative methodology
      demonstrates the suitability of anion exchange SPE and LC-MS/MS for the study of
      steroid hormones phase II metabolism, and appears promising to investigate
      metabolic profile differences linked to the hormone administration mode or
      origin, with direct application in the field of doping controls.

PMID- 12231124
TI  - Palliative Care: the World Health Organization's global perspective.

PMID- 12231125
TI  - International Association for the Study of Pain: update on WHO-IASP activities.

PMID- 12231127
TI  - A model to guide patient and family care: based on nationally accepted principles
      and norms of practice.

PMID- 12231126
TI  - The International Association for Hospice and Palliative Care: international
      activities and initiatives.

PMID- 12231128
TI  - The European Association for Palliative Care.

PMID- 12231129
TI  - The Asia Pacific Hospice Palliative Care Network: a network for individuals and
      organizations.

PMID- 12231130
TI  - The European Association for Palliative Care initiative in Eastern Europe.

PMID- 12231131
TI  - Working with regulators to improve the standard of care in pain management: the
      U.S. experience.

PMID- 12231132
TI  - Practicing palliative care in resource-poor settings.

PMID- 12231133
TI  - Improving access to opioid analgesics for palliative care in India.

PMID- 12231134
TI  - The status of pediatric palliative care in Europe.

PMID- 12231135
TI  - Argentina: Palliative care status 2002.

PMID- 12231136
TI  - Australia: state of palliative service provision 2002.

PMID- 12231137
TI  - Canada: palliative care and cancer pain.

PMID- 12231138
TI  - China: status of pain and palliative care.

PMID- 12231139
TI  - Croatia: development of a hospice movement and palliative care.

PMID- 12231140
TI  - Germany: Cancer pain and palliative care--current situation.

PMID- 12231141
TI  - Hungary: palliative care--a new challenge.

PMID- 12231142
TI  - Kerala, India: status of cancer pain relief and palliative care.

PMID- 12231143
TI  - Italy: status of cancer pain and palliative care.

PMID- 12231144
TI  - Japan: status of cancer pain and palliative care.

PMID- 12231145
TI  - Lebanon: pain relief and palliative care.

PMID- 12231146
TI  - Lithuania: status of cancer pain and palliative care.

PMID- 12231147
TI  - Mongolia: the present situation and future of palliative care.

PMID- 12231148
TI  - Norway: development of palliative care.

PMID- 12231149
TI  - Poland: cancer pain and palliative care.

PMID- 12231150
TI  - Poland: the status of pediatric palliative care.

PMID- 12231151
TI  - Romania 2002: cancer pain and palliative care.

PMID- 12231152
TI  - Russia: the State-of-the-Art of palliative care.

PMID- 12231153
TI  - Slovakia: cancer pain management and palliative care.

PMID- 12231154
TI  - Slovenia: status of palliative care and pain relief.

PMID- 12231155
TI  - South Africa: the status of palliative care.

PMID- 12231156
TI  - Spain: the WHO Demonstration Project of Palliative Care Implementation in
      Catalonia: results at 10 Years (1991-2001).

PMID- 12231157
TI  - Spain: palliative care programs in Spain, 2000: a national survey.

PMID- 12231158
TI  - Uganda: current status of palliative care.

PMID- 12231159
TI  - Uganda: initiating a government public health approach to pain relief and
      palliative care.

PMID- 12231160
TI  - United States: overview of cancer pain and palliative care.

PMID- 12231163
TI  - Nanoparticles--the next big thing?

PMID- 12231164
TI  - Adult versus embryonic stem cells: it's still a tie.

PMID- 12231165
TI  - Peptide-retargeted adenovirus encoding a tissue inhibitor of metalloproteinase-1
      decreases restenosis after intravascular gene transfer.
AB  - In this study we have attached cyclic targeting peptides by way of a poly-lysine
      spacer on the surface of an adenovirus using a transglutaminase enzymatic
      reaction to enhance transduction efficiency and to modify tissue tropism in vivo.
      Nuclear targeted lacZ- and TIMP-1-encoding adenoviruses were coupled to a peptide
      motif (HWGF) that can bind to matrix metalloproteinase (MMP)-2 and MMP-9.
      Modified viruses were used to evaluate gene transfer efficiency, biodistribution,
      and the effect on neointima formation following balloon denudation injury. In
      vitro, both rabbit aortic smooth muscle cells and human endothelial hybridoma
      cells demonstrated significantly increased reporter gene expression with HWGF
      modified adenoviruses (AdlacZ(HWGF)) compared with control (AdlacZ) or mismatch
      peptide-modified (AdlacZ(MM)) adenoviruses. However, in human hepatocellular Hep
      G2 cells, both AdlacZ(HWGF) and AdlacZ(MM) produced significantly lower transgene
      expression compared with the respective control viruses. In vivo, local
      intravascular catheter-mediated gene transfer of a HWGF-targeted TIMP-1-encoding
      adenovirus (AdTIMP-1(HWGF)) significantly reduced intimal thickening in a rabbit
      aortic balloon denudation model (P < 0.05) compared with the control adenovirus.
      X-Gal staining and biodistribution analyses with TaqMan RT-PCR revealed that the
      cyclic peptides altered vector tropism and, in particular, reduced transduction
      of the liver. We found that the HWGF peptide modification increased transduction
      efficiency of the adenovirus-mediated gene transfer in smooth muscle cells and
      endothelial cells in in vitro and enhanced gene transfer to the arterial wall in
      vivo; that peptide modification of adenoviruses beneficially modulated tissue
      tropism in vivo; and that efficient TIMP-1 gene transfer reduced intimal
      thickening in an established restenosis model in rabbits.

PMID- 12231166
TI  - Upstream conserved sequences of mouse leukemia viruses are important for high
      transgene expression in lymphoid and hematopoietic cells.
AB  - Highly conserved enhancer sequences located in the upstream part of the long
      terminal repeat (LTR) of murine leukemia retroviruses (MLV) were reported to
      compromise viral gene expression in multipotent embryonic cells in vitro and to
      reduce the likelihood for maintenance of retroviral gene expression in
      hematopoietic cells in vivo. We show that deletion of these sequences
      (nucleotides +37 to +95) attenuates rather than increases the transcriptional
      activity of retroviral vectors in hematopoietic cells almost independently of the
      developmental lineage (erythroid, myeloid, or lymphoid). Expression rates of
      modified vectors were reduced by as much as 34-65%, although the strong enhancer
      array located in the direct repeat of the LTR was preserved. Sequence analysis
      and electrophoretic mobility shift assays revealed the presence of a highly
      conserved binding site for NFAT (nuclear factor of activated T cells) proteins
      that immediately neighbors a known binding site for the transcription factor Yin
      Yang1 (YY1) [corrected]. Specific inactivation of the NFAT site reduced transgene
      expression in all cell types investigated and had a similar effect as the
      destruction of a neighboring SP1 motif. Combined destruction of individual motifs
      for NFAT, SP1, and E twenty-six transcription factors (ETS) resulted in a severe
      attenuation (by 40-60%) of the retroviral enhancer. These results provide novel
      clues for the manipulation of retrovirus replication and vector tropism.

PMID- 12231167
TI  - Improved foamy virus vectors with minimal viral sequences.
AB  - Foamy virus (FV) vectors show promise for gene therapy applications. However,
      existing FV vectors either retain a significant portion of the wild-type virus
      genome or are produced at low titers. We describe a transient cotransfection
      system that produces high-titer FV vectors with minimal cis-acting regions. These
      vector genomes have deletions in the gag, pol, env, and bel1-3 accessory genes,
      as well as the LTR U3 region, but retain an essential 2.5-kb cis-acting region.
      In addition, stop codons were introduced into the remaining gag sequences to
      prevent expression of viral peptides and to eliminate dominant-negative effects
      of a Gag-Pol fusion protein. Although these deleted foamy (deltaphi) vectors were
      produced at relatively low titers with our prior packaging construct, we designed
      separate helper plasmids for Gag, Pol, and Env expression that allowed us to
      routinely produce helper-free, unconcentrated vector stocks with titers of over
      10(5) transducing units/ml by four-plasmid transient transfection. The deltaphi
      vector stocks were then concentrated by ultracentrifugation to titers over 10(7)
      transducing units/ml. A deltaphi vector containing a 9.2-kb transgene cassette
      was produced at unconcentrated titers of over 10(5) transducing units/ml,
      demonstrating the utility of these deleted vectors for large therapeutic genes.

PMID- 12231168
TI  - Intramuscular administration of recombinant adeno-associated virus 2 alpha-1
      antitrypsin (rAAV-SERPINA1) vectors in a nonhuman primate model: safety and
      immunologic aspects.
AB  - We performed a series of studies in baboons to evaluate the safety of
      intramuscular administration of rAAV vector expressing the alpha-1 antitrypsin
      (AAT) gene (SERPINA1) in a nonhuman primate model. Initial experiments performed
      with an rAAV vector expressing the human SERPINA1 gene (at doses of up to 5 x
      10(12) vector genomes/kg) resulted in the generation of anti-human AAT
      antibodies, which correlated with a loss of detectable transgene expression.
      Subsequent studies made use of the baboon SERPINA1 gene tagged with a short (10
      amino-acid) c-myc tag. When animals were sacrificed, 4 months after vector
      injection, transduced myofibers showed efficient transgene expression without
      detectable humoral immune responses. Mild inflammation was observed in and near
      the sites of injection in some vector- and saline-injected animals, but serum
      creatine kinase (CK) values were normal in nearly every case. Real-time PCR was
      also performed 4 months after injection on gonadal tissue to evaluate the risk of
      germline transmission. No vector sequences were detected in the gonadal tissues
      from these animals. These studies indicate that the risks of immune reaction and
      germline transmission after intramuscular injection of rAAV-SERPINA1 in nonhuman
      primates are relatively low within the range of vector doses studied.

PMID- 12231169
TI  - A single-subunit NADH-quinone oxidoreductase renders resistance to mammalian
      nerve cells against complex I inhibition.
AB  - Numerous studies suggest that dysfunction of mitochondrial proton-translocating
      NADH-ubiquinone oxidoreductase (complex I) is associated with neurodegenerative
      disorders, such as Parkinson's disease and Huntington's disease. Development of
      methods to correct complex I defects seems important. We have previously shown
      that the single-subunit NADH dehydrogenase of Saccharomyces cerevisiae (Ndi1P)
      can work as a replacement for complex I in mammalian cells. Using a recombinant
      adeno-associated virus vector carrying the NDI1 gene, we now demonstrated that
      the Ndi1 enzyme was successfully expressed in the dopaminergic cell lines rat
      PC12 and mouse MN9D. The cells expressing the Ndi1 protein were resistant to
      known inhibitors of complex I, such as rotenone and pyridaben. In addition, the
      NDI1-transduced cells were still capable of morphological maturation as examined
      by induction of neurite outgrowth. Also, it was possible to infect the cells
      after the maturation. The expressed Ndi1 protein was located both in cell bodies
      and in neurites and was functionally active. It is conceivable that the NDI1 gene
      will be a promising tool in the treatment of neurodegenerative conditions caused
      by complex I inhibition.

PMID- 12231170
TI  - Impact of preimmunization on adenoviral vector expression and toxicity in a
      subcutaneous mouse cancer model.
AB  - Immune responses against adenoviral vectors may influence the toxicity and
      therapeutic effectiveness of adenovirus-mediated gene transfer and may be a
      limiting factor in adenovirus-mediated gene therapy. The purpose of this study
      was to determine the effects of preimmunization on intratumoral adenoviral
      transduction and systemic spread. The hypothesis was that increased doses of
      adenoviral vectors could overcome local neutralization without added systemic
      toxicity. The level and duration of gene expression were assessed as a function
      of time and dose after intratumoral delivery of adenoviral vector (AdV) encoding
      the luciferase reporter gene (AdV-luc) in a subcutaneous mouse mammary tumor
      model. Preimmunization resulted in significantly decreased gene expression in
      tumor and normal tissues (P < 0.01). The decrease was significantly greater in
      liver than in tumor. Increased AdV doses could be used to overcome the
      intratumoral inhibition without a concomitant increase in liver transduction.
      However, preimmunized animals showed greater toxicity than nai;ve animals (P <
      0.001). The preimmunized group developed histologic evidence of grade 2-3 hepatic
      toxicity and increases in the average values of hepatic enzymes. In addition,
      there was a significant increase in mortality (P < 0.01) in the preimmunized
      group (12 of 20 animals) compared with the naive group (3 of 20 animals). These
      findings suggest that although preimmunity can inhibit systemic expression from
      adenoviral vectors, at high vector doses it may potentiate hepatotoxicity.

PMID- 12231171
TI  - Efficient transduction of liver and muscle after in utero injection of lentiviral
      vectors with different pseudotypes.
AB  - In this study we investigate the efficacy of lentiviral vectors of different
      pseudotypes for gene transfer to tissues of the preimmune fetus. BALB/c fetuses
      at 14-15 days' gestation received lentiviral vectors carrying the transgene lacZ
      under the control of the human cytomegalovirus (CMV) promoter by intramuscular
      (i.m.) or intrahepatic (i.h.) injection. We pseudotyped the lentiviral vectors
      with vesicular stomatitis virus (VSV-G), with Mokola virus, or with Ebola virus
      envelope glycoproteins. We harvested the pups at time points between 5 days and 9
      months following injection and performed a detailed histologic assessment. The
      efficiency and distribution of transduction after in utero administration was
      highly dependent upon the route of administration and the pseudotype of vector
      used. Biodistribution studies showed widespread distribution of vector sequences
      in multiple tissues, albeit at very low levels, and transduced cells were found
      in significant numbers only in liver, heart, and muscle. Overall, VSV-G was the
      most efficient in transducing hepatocytes, whereas Mokola and Ebola were more
      efficient in transducing myocytes. Transduction of cardiomyocytes was observed
      after both i.m. and i.h. injection of all three vectors. Our findings of long
      term transduction of skeletal myocytes and cardiomyocytes after in utero
      administration suggest a novel strategy for the treatment of congenital muscular
      dystrophies.

PMID- 12231172
TI  - Immune response to full-length dystrophin delivered to Dmd muscle by a high
      capacity adenoviral vector.
AB  - Adenoviral vector-mediated gene transfer to skeletal muscle is a promising
      potential treatment for Duchenne muscular dystrophy. However, the immunological
      response to viral antigens and the therapeutic protein expressed by the delivered
      gene could prevent effective treatment. In this study, we investigated the immune
      response induced by adenoviral and dystrophin antigens presented by high-capacity
      adenoviral vector-mediated dystrophin and beta-galactosidase delivery to skeletal
      muscle of a mouse model that is both dystrophin-deficient and lacZ transgenic.
      Direct intramuscular gene delivery of the high-capacity adenoviral vector
      encoding full-length murine dystrophin resulted in stable expression of
      recombinant dystrophin for 5 months in mice treated as neonates and for 4 weeks
      in mice treated as adults. We observed neutralizing antibody to adenoviral
      antigens only in mice treated as adults and not in mice treated as neonates. This
      suggested that adenoviral antigens were only presented at the time of vector
      administration when the neonatal immune system was not yet mature. In contrast,
      antibodies to dystrophin were observed both in mice treated as neonates and in
      mice treated as adults. The development of an anti-dystrophin antibody response
      in mice treated with the high-capacity adenoviral vector as neonates suggested
      that dystrophin antigens were presented to the immune system at a time remote
      from the gene delivery, when the immune system was mature. Interestingly, an
      antibody response against beta-galactosidase developed late in the course of mice
      treated with the high-capacity adenoviral vector as neonates, suggesting a loss
      of tolerance to beta-galactosidase, a self-antigen in these transgenic mice. Our
      results suggest that future human trials of dystrophin gene delivery will need to
      address the potential for immunity induced by ongoing segmental degeneration of
      partially treated muscle fibers and presentation of recombinant dystrophin
      antigens in the context of a Duchenne muscular dystrophy patient.

PMID- 12231173
TI  - Systemic delivery of a high-capacity adenoviral vector expressing mouse CTLA4Ig
      improves skeletal muscle gene therapy.
AB  - Adenoviral vectors (AdV) are promising vectors for gene transfer of skeletal
      muscle. To alleviate humoral and cellular immune responses that limit successful
      gene transfer, the present study determined the route of administration of
      AdmCTLA4Ig (an adenovirus that encodes a fusion protein of mouse cytotoxic T
      lymphocyte-associated protein 4 (CTLA4) and the Fc protion of immunoglobulin G
      (IgG), CTLA4Ig) that provided optimal AdV-mediated immunosuppression. AdmCTLA4Ig
      was administered either intramuscularly (i.m.), intravenously (i.v.), or in the
      footpad (f.p.) of mice that simultaneously received an i.m. injection of an AdV
      encoding enhanced green fluorescent protein (AdEGFP). EGFP expression in muscle
      and serum levels of CTLA4Ig were higher in the i.v. and f.p. groups than the i.m.
      group 30 days after treatment. The i.v. and f.p. groups showed lower levels of
      CD4(+) and CD8(+) T-cell infiltration and decreased interferon-gamma (IFN-gamma)
      and interleukin 2 (IL-2) production by splenocytes. The T helper cell (Th) 2
      cytokine, interleukin 4 (IL-4), was increased 30 days after treatment in the i.v.
      group. Neutralizing antibodies to AdV were lower in the i.v. and f.p. groups,
      whereas total antibodies to AdV and EGFP were lower only in the f.p. group. Our
      results suggest that the optimal route of administration of AdmCTLA4Ig is i.v.,
      providing at least 2 months of stable transgene expression in muscle. The
      inhibition of the cellular immune response, especially the Th1 response, appeared
      to play a critical role in prolonging transgene expression. These results suggest
      that AdV-mediated delivery of targeted immune suppression will be a useful
      adjunct to muscle gene delivery.

PMID- 12231174
TI  - Dual targeting of adenoviral vectors at the levels of transduction and
      transcription enhances the specificity of gene expression in cancer cells.
AB  - Adenoviral (Ad) vector-mediated strategies for cancer gene therapy mandate a
      vector that is capable of efficient expression of the therapeutic gene
      specifically within the target tumor cells. In one approach to the development of
      cancer cell-specific vectors, Ad vectors have been targeted at the level of
      transduction to achieve the selective delivery of the therapeutic gene. In an
      alternative approach to the derivation of cancer cell-specific vectors, Ad
      vectors have been targeted at the level of transcription by placing the
      therapeutic gene under the control of transcriptional regulatory sequences that
      are activated in tumor cells, but not in normal cells, and therefore target
      expression selectively to the tumor cell. In this report, we demonstrate that a
      higher degree of specificity for cancer cells can be achieved by combining the
      complementary approaches of transductional and transcriptional targeting, each of
      which is imperfect or "leaky" by itself.

PMID- 12231175
TI  - Adenoviral vectors with E1A regulated by tumor-specific promoters are selectively
      cytolytic for breast cancer and melanoma.
AB  - We have previously demonstrated that a truncated form of the L-plastin promoter
      can confer tumor-specific patterns of expression on replication-incompetent
      adenoviral vector reporter and therapeutic transcription units. In this report, a
      2.5-kb truncated version of the L-plastin promoter was placed 5' to the E1A gene
      of a wild-type adenovirus. The vector generated (Ad-Lp-E1A) was directly
      cytotoxic to established breast and ovarian cancer cell lines and to primary
      explant cultures derived from ovarian cancer, but was not cytotoxic to explant
      cultures of normal mammary epithelial cells. This vector was not cytotoxic to
      cell lines in which the L-plastin E1A transcription unit was not expressed,
      whereas the same cell lines were sensitive to the cytotoxic effect of a
      replication-competent adenoviral vector in which the cytomegalovirus (CMV)
      promoter drove E1A expression. When the tyrosinase promoter/enhancer was placed
      5' to the E1A gene in the adenoviral backbone, the resulting vector (Ad-Tyr-E1A)
      was selectively toxic to melanoma cells and one percent as toxic to explants of
      ovarian cancer cells as the Ad-Lp-E1A vector. Injection of these vectors (Ad-Lp
      E1A and Ad-Tyr-E1A) into nodules derived from the MCF-7 and MDA-MB-468 human
      breast cancer cell lines and the TF-2 human melanoma cell line, respectively,
      which were growing subcutaneously in severe combined immunodeficiency (SCID)
      mice, induced regression of these tumors. Such vectors may therefore be useful in
      cancer treatment.

PMID- 12231176
TI  - Gene therapy for pyruvate dehydrogenase E1alpha deficiency using recombinant
      adeno-associated virus 2 (rAAV2) vectors.
AB  - To determine the feasibility of gene transfer to correct defects in the E1alpha
      subunit of the pyruvate dehydrogenase (PDH) complex (PDC), we constructed rAAV
      vectors that expressed PDH E1alpha, either alone or with a green fluorescent
      protein tag, from a hybrid cytomegalovirus (CMV) enhancer/chicken beta-actin (CB)
      promoter. These vectors were functional in vitro, as judged by increased
      expression of mRNA in vector-transduced deficient cell lines and correction of
      the biochemical defect in PDH activity in these cells. Approximately 30% of wild
      type levels of PDH activity were restored under conditions with which only about
      15% of cells were transduced. These same vectors were then used in vivo to
      transduce neurons within the rat striatum. Gene transfer, expression, and
      translocation into mitochondria were observed, without any obvious untoward
      effects. In vivo vector-mediated PDH expression persisted for at least 1 year
      after injection, indicating the stability of gene transfer. These studies provide
      the basis for future efforts to develop a recombinant AAV (rAAV)-based gene
      therapy approach for the correction of PDC deficiency.

PMID- 12231177
TI  - Overexpression of gibbon ape leukemia virus (GALV) receptor (GLVR1) on human
      CD34(+) cells increases gene transfer mediated by GALV pseudotyped vectors.
AB  - Retroviral transduction of CD34(+) cells on Retronectin using gibbon ape leukemia
      virus (GALV) pseudotyped vectors is inhibited by high concentrations of vector
      containing medium (VCM). Furthermore, this inhibitory activity is stable for at
      least 48 hours at 37 degrees C and partially blocks a second hit with a GALV
      pseudotyped vector. We hypothesized that this inhibition was due to interference
      at the receptor level between infectious and noninfectious vector particles and
      that it might be possible to overcome it by increasing receptor expression on
      target cells. Activation of protein kinase C in CD34(+) cells with the phorbol
      ester PMA (phorbol 12-myristate 13-acetate) increased the mRNA level of the GALV
      receptor (GLVR1) and the transduction efficiency (TE), and fully reversed the
      inhibition of transduction seen with high-titer GALV VCM. A murine stem cell
      virus (MSCV) vector with the GLVR1 receptor and green fluorescent protein cDNAs
      (MGLIG) was used to transduce fibroblasts, and clones expressing different levels
      of GLVR1 were isolated. The TE of these cells using a GALV vector correlated with
      the level of GLVR1 expression. When CD34(+) cells or K562 cells were first
      transduced with MGLIG and then with high-titer GALV VCM, no inhibition of
      transduction was seen. The low level of GLVR1 expression limits gene transfer to
      K562 and CD34(+) cells using GALV pseudotyped vectors, especially in the presence
      of high-titer VCMs.

PMID- 12231178
TI  - In vivo generation of dendritic cells by intramuscular codelivery of FLT3 ligand
      and GM-CSF plasmids.
AB  - Dendritic cells (DCs) are the major cells responsible for the uptake and the
      transport of antigens to regional lymphoid tissues and for the presentation of
      antigenic peptides to T cells. They are highly effective in immunotherapy.
      However, in lymphoid and other tissues, DCs constitute only a small population
      and are difficult to isolate in large numbers. Our objective was to devise a
      method with which to rapidly expand splenic DCs in vivo. We accomplished this by
      intramuscular injection of plasmids encoding mouse granulocyte-macrophage colony
      stimulating factor (GM-CSF) and fms-like tyrosine kinase 3-ligand (FLT3-L). Gene
      transfer was amplified by electroporation. Both cytokine vectors significantly
      increased DC numbers, but they were more effective in combination. When either
      control plasmid (Blank), or FLT3-L or GM-CSF expression plasmids were injected
      individually, the mean numbers of CD11c(+)/MHC II(+) DCs in spleen cell
      suspensions were, respectively, 6, 11, and 23 million. When FLT3-L and GM-CSF
      plasmids were codelivered, this increased to 36 million. Peak levels occurred 7
      days postinjection of DNA. To further characterize these DCs, we stained them
      with myeloid (CD11b, F4/80)- and lymphoid (CD8alpha)-related markers. FLT3-L cDNA
      favored lymphoid DC expansion and GM-CSF cDNA favored myeloid DC expansion,
      whereas combined treatment expanded both types with a myeloid predominance. We
      confirm the ability of these DCs to present antigen to CD4(+) T cells and to
      stimulate in mixed lymphocyte cultures. We demonstrate that DCs can be rapidly
      expanded by this simple gene transfer method, which has numerous potential
      applications.

PMID- 12231179
TI  - Novel prostate-specific promoter derived from PSA and PSMA enhancers.
AB  - The expression of prostate-specific membrane antigen (PSMA) and prostate-specific
      antigen (PSA), two well characterized marker proteins, remains highly active in
      the hormone refractory stage of prostate cancer. In this study, an artificial
      chimeric enhancer (PSES) composed of two modified regulatory elements controlling
      the expression of PSA and PSMA genes was tested for its promoter activity and
      tissue specificity using the reporter system. As a result, this novel PSES
      promoter remained silent in PSA- and PSMA-negative prostate and non-prostate
      cancer cell lines, but mediated high levels of luciferase in PSA- and PSMA
      expressing prostate cancer cell lines in the presence and absence of androgen. To
      determine whether PSES could be used for in vivo gene therapy of prostate cancer,
      a recombinant adenovirus, Ad-PSES-luc, was constructed. Luciferase activity in
      prostate cancer cell lines mediated by Ad-PSES-luc was 400- to 1000-fold higher
      than in several other non-prostate cell lines, suggesting the high tissue
      specificity of the PSES promoter in an adenoviral vector. Finally, recombinant
      virus Ad-PSES-luc was injected into mice to evaluate the tissue-discriminatory
      promoter activity in an experimental animal. Unlike Ad-CMV-luc, the luciferase
      activity from systemic injection of Ad-PSES-luc was fairly low in all major
      organs. However, when injected into prostate, Ad-PSES-luc drove high luciferase
      activity almost exclusively in prostate and not in other tissues. Our results
      demonstrated the potential use of PSES for the treatment of androgen-independent
      prostate cancer patients.

PMID- 12231180
TI  - Feasibility of using autologous transplantation to evaluate hematopoietic stem
      cell-based gene therapy strategies in transgenic mouse models of human disease.
AB  - Histoincompatibility between murine donors and recipients of bone marrow (BM)
      transplants reduces engraftment, and this compromises assessment of hematopoietic
      stem cells (HSCs) in certain transgenic mice. To study HSCs in the S+S-Antilles
      mouse model of human sickle cell disease (SCD), we developed an autotransplant
      protocol. Initial experiments showed no differences between S+S-Antilles mice and
      normal C57BL/6 (+/+) mice in their radiosensitivity or baseline hematopoietic
      progenitor numbers. The kinetics of red blood cell (RBC) replacement post
      transplant in +/+ recipients of mixtures of transgenic and +/+ BM cells also
      showed no competitive advantage of the +/+ cells. BM cells were then aspirated
      from mice 4 days after 5-fluorouracil treatment, transduced with a green
      fluorescent protein (GFP)-encoding retrovirus, and transplanted into the same
      recipients that, just before transplant, were irradiated with 800 cGy. We
      subsequently detected high levels of GFP(+) RBCs (21-79%) and white blood cells
      (WBCs; 35-88%) in the blood for 11 months and showed that transduced HSCs
      regenerated in the primary mice also repopulated secondary mice. These findings
      provide a generally applicable protocol for performing autotransplants in mice
      and forecast the potential utility of this approach in assessing HSC-based gene
      therapy protocols in transgenic mouse models of many human diseases.

PMID- 12231181
TI  - Photoimmunosuppression.

PMID- 12231182
TI  - Sources and measurement of ultraviolet radiation.
AB  - Ultraviolet (UV) radiation is part of the electromagnetic spectrum. The
      biological effects of UV radiation vary enormously with wavelength and for this
      reason the UV spectrum is further subdivided into three regions: UVA, UVB, and
      UVC. Quantities of UV radiation are expressed using radiometric terminology. A
      particularly important term in clinical photobiology is the standard erythema
      dose (SED), which is a measure of the erythemal effectiveness of a UV exposure.
      UV radiation is produced either by heating a body to an incandescent temperature,
      as is the case with solar UV, or by passing an electric current through a gas,
      usually vaporized mercury. The latter process is the mechanism whereby UV
      radiation is produced artificially. Both the quality (spectrum) and quantity
      (intensity) of terrestrial UV radiation vary with factors including the elevation
      of the sun above the horizon and absorption and scattering by molecules in the
      atmosphere, notably ozone, and by clouds. For many experimental studies in
      photobiology it is simply not practicable to use natural sunlight and so
      artificial sources of UV radiation designed to simulate the UV component of
      sunlight are employed; these are based on either optically filtered xenon arc
      lamps or fluorescent lamps. The complete way to characterize an UV source is by
      spectroradiometry, although for most practical purposes a detector optically
      filtered to respond to a limited portion of the UV spectrum normally suffices.

PMID- 12231183
TI  - Ultraviolet radiation-induced erythema in human skin.
AB  - We have evaluated UVR-induced erythema in previously unexposed buttock skin of
      volunteers of skin types I, II, III, and IV. Studies were done with solar
      simulated radiation (SSR), UVB, and UVAI and we determined the just perceptible
      minimal erythema dose (MED) and, in some cases, quantified erythema with a
      reflectance device. The results show that there is a trend for increased SSR MED
      with skin type, with the MED of skin type IV being approximately twice that of
      skin type I, a smaller difference than one might have expected. However, there is
      a very considerable overlap of MED between skin types which shows that MED is a
      very poor indictor of skin type. Quantitative dose-response and time course
      studies with SSR and UVAI showed broadly similar responses when comparable MED
      based exposures were given. We used our data to test the new concept of the
      standard erythema dose (SED) with two different erythema action spectra, and
      confirmed that the SED approach works with the different UVR sources that we
      studied.

PMID- 12231184
TI  - Ultraviolet radiation and the contact hypersensitivity reaction in mice.
AB  - The article reviews the application of the contact hypersensitivity assay in mice
      to the science of photoimmunology. The contact hypersensitivity (CHS) reaction,
      which is suppressed by UV irradiation in mice similarly to their ability to
      respond immunologically to skin tumors, has been used very profitably to reveal
      many of the regulating factors that control photoimmunosuppression, such as the
      identity of the photoreceptors that initiate immunosuppression, the defects
      induced in the cutaneous antigen presenting pathway, the local cytokine
      imbalance, and the protective intervention by various molecules, drugs, or
      interacting UV wavebands. Technical hints to optimize the measurement of the CHS
      response are suggested, including information on UV radiation wavebands and
      dosages and sensitivities of different mouse strains.

PMID- 12231185
TI  - Ultraviolet radiation-induced immunosuppression of delayed-type hypersensitivity
      in mice.
AB  - Ultraviolet (UV) radiation present in sunlight plays a critical role in the
      initiation and promotion of nonmelanoma skin carcinogenesis and immune
      suppression. The immune suppressive effects of UV have been identified as a risk
      factor for skin cancer induction. For these reasons, scientists have focused on
      elucidating the mechanisms of UV-induced immune suppression to better understand
      the pathogenesis of skin cancer induction. A hallmark of UV-induced immune
      suppression is the generation of antigen-specific suppressor T cells. These
      suppressor cells have been shown to suppress antitumor immunity as well as other
      cell-mediated responses such as delayed-type hypersensitivity (DTH) reactions.
      Due to the excessive cost and time involved in traditional UV carcinogenic
      experiments, scientists have opted to use UV-induced suppression of DTH reactions
      as a surrogate model. DTH has been, and continues to be, a widely used assay
      system to measure in vivo immune function. Although somewhat unsophisticated by
      today's standards, this assay has great advantages because it presents a fast,
      inexpensive, and reliable model system to help dissect the mechanisms involved in
      UV-induced immune suppression. Furthermore, the murine model of DTH enables
      scientists to perform additional procedures, such as adoptive transfer studies
      with suppressor T cells, which are currently unavailable with human subjects.

PMID- 12231186
TI  - Measurement of ultraviolet radiation-induced suppression of recall contact and
      delayed-type hypersensitivity in humans.
AB  - This article describes methodology used for assessment of ultraviolet radiation
      induced suppression of recall responses in humans. Nickel allergy is common in
      the general population and patch testing of nickel-allergic volunteers provides a
      convenient model of contact hypersensitivity. Similarly, Mantoux-positive
      volunteers, recruited from within hospital staff, are used as a model for delayed
      type hypersensitivity. Use of secondary rather than primary immune responses
      allows placement of multiple test sites on each volunteer. Further, each
      volunteer acts as his or her own unirradiated control. This enables UV
      immunosuppression to be studied with relatively few human volunteers, and makes
      determination of UV immunosuppression dose responses feasible in human subjects.
      The method can also be used for assessment of the level of immune protection
      afforded by agents such as sunscreens or biologically active substances.

PMID- 12231187
TI  - Polymorphisms in the TNF region confer susceptibility to UVB-induced impairment
      of contact hypersensitivity induction in mice and humans.
AB  - Acute, low-dose ultraviolet B radiation protocols impair induction of contact
      hypersensitivity (CHS) to highly reactive haptens in some mice and humans (UVB
      susceptible) but not others (UVB-resistant). These deleterious effects of
      ultraviolet radiation appear to be mediated in part by tumour necrosis factor
      alpha (TNF-alpha), which is released from, or accumulates in, UVB-exposed skin.
      To test the hypothesis that a polymorphism of the Tnfa locus governs the UVB-S
      and UVB-R phenotypes, studies have been conducted in genetically disparate
      strains of mice. Mice carrying the Tnf(d) allele [with precisely 14 (CA) repeats
      in the promoter region] display the UVB-R phenotype, whereas mice with different
      Tnf alleles [with (CA) repeats of </>14] display the UVB-S phenotype. Molecular
      genetic studies of the TNF region of HLA in humans displaying either the UVB-S or
      UVB-R phenotype reveal a significant increase in the frequencies of TNFa2 in UVB
      S individuals (P=0.00032) and of TNFd3 in UVB-R individuals (P=0.012). Moreover,
      DNA sequencing analyses of five single-nucleotide polymorphisms (SNPs) of the TNF
      promoter region revealed a significant increase in the frequency of TNF/-863A
      (P=0.015). We propose that the TNF region dictates susceptibility to the
      deleterious effects of UVB radiation on the induction of contact hypersensitivity
      in both mice and humans, and that the UVB-S-promoting polymorphisms significantly
      promote the risk of sunlight-induced skin cancer in humans.

PMID- 12231188
TI  - Measurement of UVB-Induced DNA damage and its consequences in models of
      immunosuppression.
AB  - Exposure to UVB results in formation of cyclobutane pyrimidine dimers (CPDs) and
      6-4 photoproducts in DNA. These can be quantified by a variety of techniques
      including alkaline gel electrophoresis, ELISAs, Southwestern blotting, and
      immunohistochemistry. Damage to DNA results in activation of damage response
      pathways, as indicated by Western blotting using antibodies specific for p53 and
      breast cancer-associated gene 1 (BRCA1) phosphorylation. The signal from DNA
      damage to activation of these response pathways appears to be mediated by FKBP12
      rapamycin-associated protein (FRAP), since these phosphorylation events are
      blocked by rapamycin. UVB-induced DNA damage also leads to induction of
      immunosuppressive cytokines including tumor necrosis factor alpha (TNF-alpha) and
      interleukin (IL)-10 in skin. Induction of TNF-alpha by UVB is readily detectable
      in cultured normal human epidermal keratinocytes (NHEKs) using ELISA, while
      induction of IL-10 is readily detectable in cultured mouse keratinocytes but not
      in NHEKs. Induction of DNA damage by liposome-encapsulated HindIII results in
      induction of immunosuppressive responses similar to UVB. Clinical testing shows
      that liposome-encapsulated T4 endonuclease V or photolyase stimulates repair of
      CPDs in the skin of human subjects, and prevents UVB-induced immunosuppression.
      Stimulation of repair and prevention of immunosuppression have been linked to
      prevention of skin cancer by liposome-encapsulated T4 endonuclease V in repair
      deficient xeroderma pigmentosum patients.

PMID- 12231189
TI  - Studies to determine the immunomodulating effects of cis-urocanic acid.
AB  - Exposure to ultraviolet (UV) radiation, particularly the UVB wavelengths, leads
      not only to DNA damage but also to suppression of cell-mediated immunity to
      antigens encountered shortly after the irradiation. One initiator of this complex
      process is cis-urocanic acid (cis-UCA), which is formed from the naturally
      occurring trans isomer in the epidermis on absorption of UV. cis-UCA has been
      shown to have immunomodulating properties in a variety of in vivo and in vitro
      experimental systems, although its mechanism of action is not yet clear. This
      article covers methods of preparing cis-UCA and of analyzing UCA isomers in
      various human and mouse tissues. Experiments that demonstrate that cis-UCA is
      immunosuppressive are described. The final section deals with the preparation and
      characterization of a monoclonal antibody with specificity for cis-UCA.

PMID- 12231190
TI  - Determining the role of cytokines in UV-induced immunomodulation.
AB  - Ultraviolet radiation exposure damages DNA and promotes the development of skin
      cancer. In addition, UV exposure suppresses the immune response. Although the
      mechanism by which epidermal exposure to UV induces systemic immune suppression
      is not fully understood, it is clear that cytokines are involved. Therefore,
      quantitative measurement of cytokines is a critical aspect of modern research
      techniques. Determining the level of synthesis and secretion of cytokines in vivo
      or in vitro can be achieved through several possible techniques, depending on the
      sampling size, its physical state, and the type of answers required to test the
      hypothesis. When studying transcriptional activation, the level of cytokine mRNA
      is often determined using reverse transcription polymerase chain reaction (RT
      PCR), ribonuclease protection assay (RPA), or Northern blot. Quantitative
      determinations of specific protein levels require a capture ELISA. As with any
      analytical technique, there are compromises among expense of sensitivity, labor,
      and time. These methods are discussed as they pertain to surveying cytokine
      induction and their relative usefulness to the laboratory scientist.

PMID- 12231191
TI  - Mast cells, neuropeptides, histamine, and prostaglandins in UV-induced systemic
      immunosuppression.
AB  - There is a direct correlation between dermal mast cell prevalence in dorsal skin
      of different mouse strains and susceptibility to UVB-induced systemic
      immunosuppression; highly UV-susceptible C57BL/6 mice have a high dermal mast
      cell prevalence while BALB/c mice, which require considerable UV radiation for
      50% immunosuppression, have a low mast cell prevalence. There is also a
      functional link between the prevalence of dermal mast cells and susceptibility to
      UVB- and cis-urocanic acid (UCA)-induced systemic immunosuppression. Mast cell
      depleted mice are unresponsive to UVB or cis-UCA for systemic immunosuppression
      unless they are previously reconstituted at the irradiated or cis-UCA
      administered site with bone marrow-derived mast cell precursors. cis-UCA does not
      stimulate mast cell degranulation directly. Instead, in support of studies
      showing that neither UVB nor cis-UCA was immunosuppressive in capsaicin-treated,
      neuropeptide-depleted mice, cis-UCA-stimulated neuropeptide release from sensory
      c-fibers which, in turn, could efficiently degranulate mast cells. Studies in
      mice suggested that histamine, and not tumor necrosis factor alpha (TNF-alpha),
      was the product from mast cells that stimulated downstream immunosuppression.
      Histamine receptor antagonists reduced by approximately 60% UVB and cis-UCA
      induced systemic immunosuppression. Indomethacin administration to mice had a
      similar effect which was not cumulative with the histamine receptor antagonists.
      Histamine can stimulate keratinocyte prostanoid production. We propose that both
      histamine and prostaglandin E(2) are important in downstream immunosuppression;
      both are regulatory molecules supporting the development of T helper 2 cells and
      reduced expression of type 1 immune responses such as a contact hypersensitivity
      reaction.

PMID- 12231192
TI  - Increased dermal mast cell prevalence and susceptibility to development of basal
      cell carcinoma in humans.
AB  - Exposure to ultraviolet B (UVB) radiation (280-320 nm) is the primary etiologic
      factor associated with the development of basal cell carcinoma (BCC). The
      outgrowth of these keratinocyte-derived skin lesions is enhanced by the ability
      of UVB to impair an immune response that would otherwise eliminate them. Studies
      in a range of inbred mouse strains as well as mast cell-depleted mice
      reconstituted with mast cell precursors support a functional link between
      histamine-staining dermal mast cells and the extent of susceptibility to UVB
      induced systemic immunomodulation. Humans, like mouse strains, display variations
      in dermal mast cell prevalence. In a study of Danish and South Australian BCC
      patients and control subjects, one 4-mm punch biopsy of non-sun-exposed buttock
      skin was sampled from each participant. This skin site was investigated to avoid
      any changes in mast cell prevalence caused by sun exposure. Two sections (4
      microm) per biopsy were immunohistochemically stained for detection of histamine
      containing dermal mast cells. Computer-generated image analysis evaluated dermal
      mast cell prevalence in both sections by quantifying the total number of mast
      cells according to the total dermal area (expressed as mast cells per square
      millimeter). This technique enabled us to detect heterogeneity of dermal mast
      cell prevalence in buttock skin between individuals and provided evidence of an
      association between high dermal mast cell prevalence and BCC development in two
      diverse populations. We hypothesize that mast cells function in humans, as in
      mouse strains, by initiating immunosuppression following UV irradiation and,
      thereby, allowing a permissive environment for the development of BCC. Thus, a
      high dermal mast cell prevalence as demonstrable in buttock skin is a significant
      predisposing factor for development of BCC in humans.

PMID- 12231193
TI  - Neuropeptides and neuroendocrine hormones in ultraviolet radiation-induced
      immunosuppression.
AB  - Exposure of the skin to ultraviolet radiation (UVR) can lead to deleterious
      effects such as sunburn, photoaging, and the development of skin cancer. UVR has
      also been shown to reduce local and systemic immune responses in humans and
      animals. In the recent past it has become clear that neuropeptides mediate some
      of the effects of UVR-induced immunosuppression. Among the neuropeptides released
      from cutaneous nerves after exposure to UVR, calcitonin gene-related peptide
      (CGRP) has been examined most extensively. It appears to lead to a reduction of
      contact hypersensitivity by inducing mast cells to degranulate and thus release
      tumor necrosis factor alpha (TNF-alpha) and, most likely, interleukin (IL)-10.
      Nitric oxide, which is coreleased with CGRP, seems to also play a role in
      immunosuppression through a yet undiscovered mechanism of action, while substance
      P may have counterregulatory effects. New evidence suggests that the release of
      neuropeptides from cutaneous sensory c-fibers after UVR is induced by
      keratinocyte-derived nerve growth factor. UVR can also induce epidermal and some
      dermal cells, such as melanocytes, keratinocytes, and dermal microvascular
      epithelial cells, to produce proopiomelanocortin (POMC) and its derivatives. The
      POMC product alpha-melanocyte-stimulating hormone (alpha-MSH) has been implicated
      in suppression of contact hypersensitivity and induction of hapten-specific
      tolerance, most likely by inducing keratinocytes and monocytes to produce the
      anti-inflammatory cytokine IL-10. Other POMC derivatives have not yet been
      investigated with regard to a possible role in UVR-induced effects on immunity.

PMID- 12231194
TI  - Cell surface and cytokine phenotypes of skin immunocompetent cells involved in
      ultraviolet-induced immunosuppression.
AB  - Immunocellular migrations out of and into the skin and modulations of functional
      cell surface molecules on antigen-presenting cells (APCs), as well as their
      immunoregulatory cytokine production, are important factors involved in the
      mechanism of UV-induced immunosuppression and tolerance. Of particular interest
      here are the effects of low-dose UVB exposures that can suppress the ability of a
      contact sensitizer to induce contact hypersensitivity (CHS) through the site
      (local immunosuppression) without inducing suppression of CHS induced through
      skin distant to the UV exposure. Such UV-irradiated skin has many changes with
      respect to composition of immunocompetent cells and cytokine production. After UV
      exposure, Langerhans cells/dendritic cells migrate from the skin to draining
      lymph nodes (DLNs) as they do from contact sensitizer-applied normal skin. On the
      other hand, UV causes monocytic/macrophagic cells to infiltrate into the dermis
      and then into the epidermis; these can also be shown to be induced by contact
      sesitizers to migrate to DLNs. Alterations in cell surface and immunoregulatory
      cytokine phenotypes of the cutaneous APCs in both the skin and DLNs are critical
      for CHS suppression and tolerance induction. Here we describe the phenotypic
      changes of immunocompetent cells in UV-irradiated skin in regard to CHS
      suppression and tolerance and methodologies to approach this area.

PMID- 12231195
TI  - Ultraviolet radiation, resistance to infectious diseases, and vaccination
      responses.
AB  - Exposure to ultraviolet (UV) radiation, as in sunlight, can modulate immune
      responses in animals and humans. This immunomodulation can lead to positive
      health effects especially with respect to certain autoimmune diseases and
      allergies. However, UV-induced immunomodulation has also been shown to be
      deleterious. Experimental animal studies have revealed that UV exposure can
      impair resistance to many infectious agents, such as bacteria, parasites,
      viruses, and fungi. Importantly, these effects are not restricted to skin
      associated infections, but also concern systemic infections. The real
      consequences of UV-induced immunomodulation on resistance to infectious diseases
      are not known for humans. Risk estimations have been performed through
      extrapolation of animal data, obtained from infection models, to the human
      situation. This estimation indicated that UV doses relevant to outdoor exposure
      can impair the human immune system sufficiently to have effects on resistance to
      infections. To further quantify and validate this risk estimation, data, e.g.,
      from human volunteer studies, are necessary. Infection models in humans are not
      allowed for ethical reasons. However, vaccination against an infectious disease
      evokes a similar immune response as the pathogen and thereby provides an
      opportunity to measure the effect of UV radiation on the immune system and an
      estimate of the possible consequences of altered resistance to infectious agents.
      Effects of controlled UVB exposure on immune responses after hepatitis B
      vaccination have been established in mice and human volunteers. In mice, cellular
      and Th1-associated humoral immune responses to hepatitis B were significantly
      impaired, whereas in human volunteers no significant effect of UVB on these
      responses could be found. Preliminary data indicate that cytokine polymorphisms
      might be, at least in part, responsible for interindividual differences in immune
      responses and in susceptibility to UVB-induced immunomodulation. In addition,
      adaptation to UV exposure needs to be considered as a possible explanation for
      the difference between mice and humans that was observed in the hepatitis B
      vaccination model.

PMID- 12231196
TI  - Ultraviolet radiation and tumor immunity.
AB  - Ultraviolet (UV) radiation induces a specific tolerance toward UV-induced skin
      tumors. This phenomenon has been known and studied for more than 25 years, but
      the mechanisms by which protective tumor immunity or tumor tolerance is induced
      are still largely obscure. In parallel with these studies, short-term assays on
      UV-induced immunosuppression and tolerance toward simple chemicals (e.g.,
      dinitrochlorobenzene) have been analyzed, particularly with respect to the role
      of cytokines (most notably, interleukin (IL)-10 vs IL-12). However, these short
      term assays are not likely to be fully adequate models of the long-term UV
      induced tumor tolerance. The important nodal points of action in these immune
      reactions appear to be the T cells and the antigen-presenting cells (APCs) that
      prime them. The main focus should probably be on CD8(+) T cells as the ultimate
      effector of the cytotoxic response against UV-induced skin cancers. APC-mediated
      activation of these cells depends strongly on cosignaling of CD4(+) T cells. In a
      tumor tolerant state the activity of the cytotoxic CD8(+) T cells appears to be
      inhibited through CTLA-4(+) and natural killer T cells. The latter cells are CD1
      restricted, which indicates the importance of "unconventional" antigens to UV
      induced tumor tolerance.

PMID- 12231197
TI  - Use of mutant mice in photoimmunological and photocarcinogenic investigations.
AB  - The mechanisms underlying UV-induced immunosuppression and the development of UV
      induced skin cancer have been intensively investigated for decades. In
      particular, UV-induced DNA damage and UV-induced suppression of cellular immune
      responses were analyzed in great detail. During this time, several cellular and
      genetic pathways were identified, that are involved in photoimmunology and
      photocarcinogenesis. However, the direct effects of the complex UV-induced
      pathways on immunosuppression or on cutaneous tumor generation in vivo have not
      been able to be characterized with certainty so far. With the increasing
      availability of mutant mice that lack or overexpress certain genes, more
      information can be obtained with respect to the functional importance of
      individual gene products and the signaling pathways involved in UV-mediated
      immunomodulation and cancer development. This article is an overview of the
      results of UV-induced immunosuppression and photocarcinogenesis experiments
      obtained in different mutant mice.

PMID- 12231198
TI  - Role of immunomodulation in diseases responsive to phototherapy.
AB  - Within the last two decades phototherapy has turned out to be a major therapeutic
      strategy in dermatology and thus has significantly influenced the treatment of
      many dermatoses. The goals of therapeutic photomedicine are the suppression of
      ongoing disease processes and, more importantly, the prevention, modulation, or
      abrogation of pathogenic mechanisms causing the disease. Therapeutic
      photomedicine has been largely empirical and most of it is still empirical today.
      However, parts of it are already based on the advances in photoimmunology and
      molecular biology. Although, we are far from a detailed understanding of the
      mechanisms underlying phototherapy, there is increasing evidence that
      phototherapy acts via modulation of the immune system. Most of the effects of
      both ambient and therapeutic ultraviolet radiation are immunosuppressive in
      nature.

PMID- 12231200
TI  - Matrix metalloproteinases and their inhibitors in bone remodelling following
      distraction osteogenesis of the sheep mandible.
AB  - AIM: Matrix metalloproteinases (MMPs), together with their tissue inhibitors
      (TIMPs), are responsible for the controlled degradation of collagen and other
      matrix substrates in bone and other tissues. This study evaluated the expression
      of MMPs and TIMPs in bony remodelling in a bilateral sheep mandible model up to
      12 months following lengthening by distraction osteogenesis. METHODOLOGY: Sheep
      mandibles were harvested 3, 6, 9 or 12 months following lengthening by bilateral
      mandibular distraction (1 mm/day for 20 days). Undistracted sheep mandibles were
      used as controls. The tissues underwent routine histology and immunohistochemical
      staining with monoclonal antibodies specific to MMPs 1-3 and TIMP-1, 2. Matrix
      and cell staining was assessed using a semi-quantitative analysis. RESULTS:
      Matrix metalloproteinases and their tissue inhibitors (TIMPs) expression levels
      were marked at 3 months and decreased thereafter becoming similar to undistracted
      controls by 12 months. The histologic development of mature lamellar cortical
      bone was similar to undistracted controls by 9 months following distraction.
      CONCLUSIONS: A temporal expression of MMPs and TIMPs was found in distraction
      osteogenesis. MMPs and TIMPS may, in part, reflect the state of bony remodelling
      following mandibular lengthening by distraction osteogenesis. Matrix
      metalloproteinases and TIMP expression were comparable to undistracted controls
      by 12 months, suggesting that equilibrium had been achieved and that bony relapse
      is unlikely.

PMID- 12231199
TI  - Is early osteodistraction a solution for the ascending ramus compartment in
      hemifacial microsomia? A literature study.
AB  - AIM: In hemifacial microsomia, osteodistraction before skeletal maturation claims
      to induce both bone- and soft-tissue generation in such a way that conventional
      bone grafting and soft-tissue grafts are not necessary. Early osteodistraction in
      facial microsomia would have a positive effect on the 'functional matrix', and
      allow symmetrical vertical and sagittal expansion of the midface and mandible.
      The aim of this literature survey was to find evidence for this hypothesis by
      analysing long-term follow-up reports on distraction histiogenesis in the
      ascending ramus. MATERIAL: Only eight published studies were found, of which only
      two had more than ten patients, two were case reports, and three were from the
      same institution. RESULT: Invariably, the results pointed towards over
      correction, repeated osteodistraction procedures, soft-tissue stretching (but no
      lateral augmentation), and to soft-tissue complications. The studies did not
      allow a conclusion to be made as whether increased vertical gain in the ascending
      ramus was unstable because of decreased growth on the affected side, inborn or
      iatrogenic, or due to resorption of the bone generated by distraction. To date,
      there is no evidence that osteodistraction produces better results and has lower
      morbidity than conventional growth centre transplantation and separate soft
      tissue augmentation. CONCLUSION: Recommendations for prospective studies are:
      sharp differentiation between the four Pruzansky-Kaban mandibular types, multi
      centre study of a surgical protocol to increase the sample number using a
      standard three-dimensional evaluation protocol, and differentiation between
      decreased growth and collapse of the newly generated bone.

PMID- 12231201
TI  - The mandibular canal of the "old man" of Cro-Magnon: anatomical-radiological
      study.
AB  - INTRODUCTION: The radiological study of the 'old man' of Cro-Magnon mandible
      complements the one published about the mandibular canal of the "Neanderthal Man"
      of La Chapelle-aux-Saints with which it is compared. OBJECTIVE: The purpose of
      this study was to explore the internal structure of this famous fossil. MATERIAL
      AND METHODS: The mandible of the "old man" of Cro-Magnon (22,000 BC) was studied
      with panoramic radiography and CT scanning. RESULTS: The mandibular canal is
      similar to that of modern man. The images obtained are of a good quality and can
      be used for analysis of the internal structures of bony fossils. CONCLUSION: The
      mandible of the "old man" of Cro-Magnon belongs to the species Homo sapiens
      sapiens.

PMID- 12231202
TI  - Experimental and comparative study of the blood supply to the mandibular cortex
      in Gottingen minipigs and in man.
AB  - INTRODUCTION: Since the blood supply to the mandibular cortex is an important
      factor for bone growth and bone repair, experimental studies on the blood supply
      in animal models (such as Gottingen minipigs) applicable to man are necessary.
      Their value depends on the requirement that the patterns of blood supply in the
      two species are similar. MATERIAL AND METHODS: Twelve Gottingen minipig mandibles
      (24 halves) and four human mandibles (eight halves) were investigated for the
      blood supply to the mandibular cortex. RESULTS: Only minor differences were found
      in blood supply to the mandibular cortex between the two species. Common to both
      was: in the cranial part of the mandible (including the condyle), the endosteal
      blood supply prevailed, whereas the periosteal blood supply predominated in the
      caudal part of the mandible (the body). Both patterns of blood supply were in
      balance in the centre section, i.e. angle and ascending ramus of the mandible.
      CONCLUSION: The present study confirms that results obtained from Gottingen
      minipigs, used as an experimental animal model, are applicable to man: three
      different types of blood supply are evident in the mandibular cortex in both
      species.

PMID- 12231203
TI  - Treatment of severe mandibular prognathism in combination with maxillary
      hypoplasia: case report.
AB  - We performed a Le Fort I osteotomy and sagittal split ramus osteotomy (Obwegeser
      Dal Pont) combined with mandibular anterior segmental osteotomy without tooth
      extraction for a patient with severe mandibular prognathism accompanied by a
      hypoplastic maxilla, anterior open bite and normal anterior mandibular vertical
      dimension. The results of facial appearance and occlusion were excellent. This
      combined surgical method appears to be satisfactory for treating severe
      mandibular prognathism with hypoplastic maxilla.

PMID- 12231204
TI  - Quantification of the neurodegenerative impact on the visual system following
      sudden retrobulbar expanding lesions - an experimental model.
AB  - INTRODUCTION: Afferent disorders of the visual system are a potential consequence
      following orbital trauma. The aim of this study was to investigate the tolerance
      of neurons in the retinal ganglion cell layer to acute expanding retrobulbar
      lesions. MATERIAL AND METHODS: In 42 male albino rats, intraorbital haemorrhage
      was simulated by transconjunctival insertion of a retrobulbar micro-balloon
      (filling volume 0.2-0.5 ml, duration of lesion 60 or 90 min). Neurodegeneration
      in the retinal ganglion cell layer was investigated by measuring the mean total
      neuron number and the mean neuron size. RESULTS: Increased retrobulbar volumes of
      0.3 ml for 60 min led to a decrease in a number of neurons by 14.5% and in size
      of the neurons by 1.7%. Prolongation of the trauma to 90 min resulted in a
      decrease in number of neurons by 48.3% and in reduction of size of neurons by
      22.1%. In contrast, a retrobulbar filling volume of 0.5 ml for 60 min resulted in
      a decrease in number of neurons by 11.4% and in size of neurons by 6.7%.
      CONCLUSION: The duration of a retrobulbar lesion leading to subsequent retinal
      ischaemia seems to be more important for neuron survival than the exerted
      pressure (once it is greater than a critical point for producing retinal
      ischaemia). The results strengthen the need for emergency treatment in cases of
      retrobulbar haemorrhage.

PMID- 12231205
TI  - Paediatric maxillofacial fractures: their aetiological characters and fracture
      patterns.
AB  - OBJECTIVE: Paediatric maxillofacial fractures are not common and carry different
      clinical features when compared with adults. To clarify the differences of
      aetiology and patterns of fractures in paediatric patients, a clinical
      retrospective analysis was performed. PATIENTS: One hundred seventy-four
      paediatric patients younger than 16 years of age treated in the First Department
      of Oral and Maxillofacial Surgery, Osaka University Dental Hospital during a 15
      year period were analysed. STUDY DESIGN: Age, sex, fracture patterns, incidence,
      common locations of the mandibular fractures and treatment were studied according
      to the patients' charts and radiographs. RESULTS: The ratio of boys to girls was
      2:1 and the largest age subgroup was 15-years old. The most common cause of
      injury was bicycle accidents (26%), followed by falls (25%). The distribution of
      causes and ages revealed that the incidence of the fall-related injuries
      decreased in patients older than 10 years, and assaults became a common cause in
      patients older than 12 years. The yearly distribution showed a decrease of the
      group between 6 and 10 years and of bicycle-related accidents in the last 5-year
      period (1992-1996). Mandibular fractures were most common (56%), followed by
      fractures of the alveolar process (31%). Condylar fracture was common in children
      younger than 14 years, especially in those below 6 years. Fractures of the
      mandibular angle were the most common in those above 13 years. CONCLUSION: These
      results document that the aetiological characters and patterns of paediatric
      maxillofacial fractures gradually shifted towards those found in adolescents.

PMID- 12231206
TI  - Pleomorphic adenoma of the parotid in childhood.
AB  - INTRODUCTION: Pleomorphic adenoma is a benign growth that most often appears in
      the parotid gland where it is the most frequent type of tumour. Its appearance in
      childhood is rare and there are no large series available in this age group for
      comparison with its presentation in adults. Surgical treatment is similar in
      children and in adults; whilst the prognosis is good, they may become malignant
      and metastasize. MATERIAL AND METHOD: In this study, we present seven parotid
      pleomorphic adenomas in childhood treated in our Department and a review of the
      literature. The following data were evaluated: sex, age, affected side, clinical
      symptoms and period of evolution of the symptoms, surgical technique applied and
      complications observed. RESULTS: The mean age at presentation was 12.4 years. All
      patients were males with the right side affected in five patients. The treatment
      was conservative superficial parotidectomy in five patients, conservative total
      parotidectomy in one, and an enucleation including a wide safety margin in the
      last case. None of the patients exhibited any permanent postoperative
      complication. The mean follow-up was 41.3 months (26-58 months).

PMID- 12231208
TI  - Access to the maxillary sinus using a bone flap on a mucosal pedicle: preliminary
      report.
AB  - INTRODUCTION: An alternative procedure to access the maxillary sinus is
      described. OBJECTIVE: To describe advantages and disadvantages of the suggested
      technique of harvesting a bone flap based on an antral mucosal pedicle. MATERIAL:
      Four patients have been operated on to remove foreign bodies or odontogenic
      cysts. RESULTS: In all four patients, removal of the lesions and foreign bodies
      was easily accomplished. CONCLUSION: The procedure described respects the morpho
      functional integrity of the sinus, is easy, quick and may be performed under
      local anaesthesia.

PMID- 12231207
TI  - The effect of external fractionated irradiation on the distribution pattern of
      extracellular matrix proteins in submandibular salivary glands of the rat.
AB  - INTRODUCTION: The aim of this study was to analyse the distribution pattern of
      extracellular matrix proteins in the irradiated and non-irradiated rat
      submandibular salivary gland in order to provide a more detailed profile of the
      radiation injury following radiotherapy of the head and neck. MATERIAL AND
      METHODS: External X-ray exposure, restricted to the left skull base and neck
      region, was performed in 60 female Wistar rats, fractionated to daily
      applications of 2 Gy, up to total dosages of 20, 40 or 60 Gy. Both submandibular
      glands were excised after supravital anaesthesia 6 months or 1 year after
      completion of the irradiation. Spatial and temporal patterns of extracellular
      matrix proteins were investigated histologically and immunohistochemically.
      RESULTS: The polyclonal anti-human antisera used, identified the same antigens in
      rat tissue as in human tissues. The alterations in staining patterns and staining
      intensities between irradiated and non-irradiated salivary glands showed
      statistically significant differences. Different structures in irradiated glands
      reacted with different intensities, e.g. nerve tissue and the basement membranes
      of excretory ducts were intensely laminin-positive, fibronectin was predominantly
      found around the excretory ducts with transition to the interstitial tissues.
      CONCLUSION: Irradiation leads to statistically significant differences in the
      amount and composition of the extracellular matrix in salivary glands. The amount
      of extracellular matrix proteins in irradiated glands is dose-dependent. The
      higher the dosage the more extracellular matrix can be expected. Consecutively,
      total dosage is associated with greater loss of acini. Scatter effects of
      irradiation have also to be recognized. Immunohistochemical studies on salivary
      glands have to consider the pretreatment status, in particular those studies that
      investigate degenerative changes.

PMID- 12231209
TI  - The role of the ubiquitin-proteasome pathway in the formation of mallory bodies.
AB  - The dynamics of Mallory body (MB) formation are difficult to follow in vivo.
      Because of the lack of an in vitro mouse hepatocyte culture model, a cellular
      extract approach was developed. In this model an immunoprecipitate was obtained
      using an antibody to cytokeratin-8 (CK-8). The isolate contained a large number
      of compounds: CK-8, ubiquitin, a frameshift mutation of ubiquitin (UBB(+1)),
      proteasomal subunits beta5 (a catalytic subunit of the 20S proteasome) and Tbp7
      (an ATPase subunit of the 26S proteasome), transglutaminase, tubulin, heat shock
      proteins 90 and 70, and MBs. In Western blots, CK-8 immunoprecipitates showed
      colocalization of these components in a complex of proteins colocalized in a high
      molecular-weight smear. When the CK-8 immunoprecipitate was incubated with the
      isolate of proteasomes and an energy generating source (ATP), the components of
      the ubiquitinated protein smear increased. These observations taken together with
      the in vivo observation that these proteins colocalized at the edge of the MB
      shown in the present study suggest that these proteins form aggregates through
      covalent binding of CK-8, ubiquitin, and the proteasomes. Covalent aggregation is
      suggested by the fact that the protein complex found in the high-molecular-weight
      smear that forms in vitro fails to dissociate in SDS. This protein complex is
      present in the CK-8 immunoprecipitates of livers forming MBs but not in control
      livers. In conclusion, the results support the concept that Mallory bodies are
      aggresomes which form as the result of the failure of the ubiquitin-proteasome
      complex to adequately eliminate cytokeratins destined for proteolysis.

PMID- 12231210
TI  - The effect of sulfasalazine on rheumatoid arthritic synovial tissue chemokine
      production.
AB  - Rheumatoid arthritis (RA) is an aggressive inflammatory disease in which
      chemokines are thought to recruit leukocytes and induce angiogenesis. The aim of
      this study was to investigate the effects of sulfasalazine (SASP) and its
      metabolites, sulfapyridine (SP), and 5-aminosalicylic acid (5ASA) on chemokine
      production by RA synovial tissue explants and interleukin (IL)-1beta-stimulated
      RA synovial tissue fibroblasts using enzyme-linked immunosorbent assays and flow
      cytometry. Synovial tissue explants from RA patients secreted a decreased amount
      of the chemokines IL-8 and growth-related gene product alpha (GROalpha) when
      treated with SASP over a broad range of concentrations based on the typical
      clinical dosage of 2 g/day. SP had a significant effect in that it decreased RA
      synovial tissue explant secretion of IL-8 (22%), GROalpha (55%), and monocyte
      chemotactic protein-1 (MCP-1) (42%) (P < 0.05). 5ASA had no effect on RA synovial
      tissue explant production of IL-8 and MCP-1, while increasing GROalpha
      production. In IL-1beta-stimulated RA synovial tissue fibroblasts, SASP
      significantly increased chemokine secretion, while SP significantly decreased IL
      8 (24%) and GROalpha (21%) secretion (P < 0.05). Flow cytometry showed that the
      number of IL-8 expressing RA synovial tissue fibroblasts did not significantly
      change following SP treatment. These data suggest that SASP may function to
      reduce inflammation in RA through the effects of its metabolite SP to reduce the
      secretion of the inflammatory chemokines IL-8, GROalpha, and MCP-1.

PMID- 12231211
TI  - Study of disabling T-cell activation and inhibiting T-cell-mediated
      immunopathology reveals a possible inverse agonist activity of CD4
      peptidomimetics.
AB  - We designed a new class of aromatically modified exocyclic peptides based on the
      structure of CD4 by engineering one of the cysteine residues in a peptidomimetic
      derived from the CDR3 region of the CD4 molecule. All three species mediate
      inhibition of T-cell proliferation at concentrations ranging from 10 to 100
      microM. The mimetics CD4-Cys and CD4-Met bind to sCD4 with affinities ranging
      from 1 to 2 microM, while CD4-Ser shows poor binding in radioisotope assay.
      Though these mimetics have similar structures, they exhibit different biochemical
      and biological functions. Activation of T-cells as measured by thymidine
      incorporation or IL-2 production revealed that CD4-Cys and CD4-Ser mimetics
      behave as classical antagonists. On the other hand, the CD4-Met species inhibited
      T-cell proliferation with an IC(50) of 30 microM but unexpectedly increased IL-2
      secretion modestly at a less than 3 microM concentration. In experimental
      autoimmune encephalitis (EAE), CD4-Ser and CD4-Cys mimetics reduced the severity
      of EAE symptoms while the CD4-Met mimetic exacerbated the conditions. We propose
      that CD4-Cys and CD4-Ser are classical antagonists, but CD4-Met may possess
      properties of an inverse agonist. The structure-activity relationship of mimetics
      reveals that a minor change in the net hydropathic value is enough to alter the
      dynamic nature of the receptor-ligand complex.

PMID- 12231212
TI  - Tumor necrosis factor-alpha antibody eluting stents reduce vascular smooth muscle
      cell proliferation in saphenous vein organ culture.
AB  - Expression of TNF-alpha a vascular smooth muscle cell (VSMC) mitogen, is up
      regulated in injured/proliferating vessel wall. Coronary stents are tested
      worldwide for their use as local drug delivery devices to address vascular
      pathophysiology. In this study we have investigated the effect of TNF-alpha
      antibody eluting stents on VSMC proliferation in human saphenous vein (HSV) organ
      culture. The adsorption and elution characteristics of TNF-alpha antibody was
      assessed using stent wires. The stents adsorbed up to 0.25 microg of TNF-alpha
      antibody/mg of stent and showed a biexponential elution curve, with 34.4% (SD
      4.4%) antibody remaining on the stent after 72 h of washing in a perfusion
      circuit. TNF-alpha antibody delivery from loaded stents to the vessel wall was
      assessed ex vivo. TNF-alpha and proliferating cell nuclear antigen (PCNA)
      expression in the vascular specimens was assessed by immunostaining or ELISAs.
      TNF-alpha ELISAs showed a significant increase in the cytokine levels from the
      vascular lysates prepared from proliferating tissue culture compared with fresh
      vein (P < 0.05). Immunohistochemical localization showed an increase in the PCNA
      positivity of VSMC from these cultures. PCNA staining was barely detected from
      the fresh tissue. However, a decrease in PCNA staining was observed from tissue
      sections of venous segments cultured with TNF-alpha antibody eluting stents. PCNA
      ELISAs demonstrated a 23.7% decline in the antigen levels from the day 7 tissue
      cultured with such loaded stents. In conclusion, activated VSMC in tissue culture
      showed an up-regulation of TNF-alpha cytokine, in association with an increase in
      the PCNA expression in the vessel wall. The local neutralization of this cytokine
      with TNF-alpha antibody eluting stents reduced VSMC proliferation in the wall. We
      suggest that TNF-alpha antibody eluting stents may limit restenosis in vivo,
      which may have important clinical benefits.

PMID- 12231213
TI  - Immunological enhancement revisited.

PMID- 12231214
TI  - Ultrastructure of the interaction between mycobacterium tuberculosis- H37Rv
      containing phagosomes and the lysosomal compartment in human alveolar
      macrophages.
AB  - The ultrastructure of the interaction between the lysosomal compartment and the
      Mycobacterium tuberculosis-containing phagosomes in human resident alveolar
      macrophages has been analyzed in detail. Our findings confirm the widely accepted
      notion that the parasitophore vacuole is made nonfusogenic by the microorganism;
      however, the association between the lysosomal compartment and the phagosomes
      does not seem to be impaired as the organelles were shown to spread around the
      ingested pathogen. Furthermore, interruptions in the phagosome membrane that
      connect the bacterial surface with the cytosol were observed.

PMID- 12231215
TI  - Experimental hyperlipidemia and the effect of NSAIDs.
AB  - The effects of ip administration of NSAIDs in experimentally induced
      hyperlipidemia in rats was studied. An isotonic solution of Triton WR1339
      (tyloxapol) was administered ip to rats one hour after ip administration of the
      examined anti-inflammatory drug. After 24 h, blood was collected for the
      determination of plasma total cholesterol (TC), LDL and trigluceride (TG)
      concentrations. The NSAIDs used in our experimental model are selective or non
      selective COX-1 inhibitors as well as one non selective COX-2 inhibitor. Most of
      the drugs significantly reduced the TC, TG and LDL concentrations in the plasma
      of hyperlipidemic rats. While studies link atheromatosis to inflammation, our
      results potentially also link anti-inflammatory activity with hypolipidemia.
      Thus, NSAIDs not only may address the inflammatory aspect of atherosclerosis but
      also may contribute directly by inducing hypolipidemia.

PMID- 12231216
TI  - The Interleukin 1-beta exonic (+3953) polymorphism does not alter in vitro
      protein secretion.
AB  - Several studies have described polymorphisms in the genes encoding interleukin
      1alpha (IL-1alpha) and IL-1beta cytokines and their implication in the onset of
      Alzheimer disease or in linkage disequilibrium with an as yet to be identified
      second locus on chromosome 2. However, these results have been associated with
      the sporadic forms of Alzheimer disease. Here we present data on the effects of
      the interleukin 1-beta exonic polymorphism (+3953) using a series of cohort
      healthy control samples and in vitro protein secretion assays.

PMID- 12231218
TI  - Abstracts of the 40th Annual Meeting of the Academy of Aphasia. New York, USA, 20
      22 October 2002.

PMID- 12231217
TI  - Arterial enlargement in response to high flow requires early expression of matrix
      metalloproteinases to degrade extracellular matrix.
AB  - This study investigated the effects of high flow and shear stress on the
      expression of matrix metalloproteinases (MMPs) and tissue inhibitor of
      metalloproteinase-2 (TIMP-2) during flow-induced arterial enlargement using a
      model of arteriovenous fistula (AVF) creation on the carotid artery with the
      corresponding jugular vein in Japanese white male rabbits. Flow increased 8-fold
      7 days after AVF. Endothelial cells (EC) and smooth muscle cells (SMC)
      proliferated with internal elastic lamina (IEL) degradation in response to high
      flow and shear stress. Expression of MMP-2 mRNA peaked at 2 days (1700-fold) and
      maintained high level expression. MMP-9 mRNA gave a 10.8-fold increase within 2
      days and decreased later. Their proteins were detected in EC and SMC. Membrane
      type-1-MMP (MT1-MMP) mRNA increased 121-fold at 3 days and maintained high
      expression. TGF-beta1 was increased after AVF. Two-peak up-regulation of Egr-1
      mRNA was recognized at 1 and 5 days of AVF. These results suggest that high flow
      and shear stress can mediate EC and SMC to express MMP-2 and MMP-9, which degrade
      cell basement membranes and IEL to induce arterial enlargement. The
      disproportional increase in MT1-MMP and TIMP-2 might contribute to MMP-2
      activation. Egr-1 and TGF-beta1 might play important roles in this process.

PMID- 12231220
TI  - Human proteomic databases: a powerful resource for functional genomics in health
      and disease.
AB  - Decoding of the genome information in terms of regulation and function will be
      the next great challenge in the life sciences in this millennium and indeed,
      today we are experiencing a rapid explosion of technology for the high throughput
      expression analysis of genes and their products (functional genomics). In
      particular, the field of proteomics is booming as proteins are often the
      functional molecules and represent important targets for the pharmaceutical
      industry. The proteomic technology is complex, and comprises a plethora of state
      of-the-art techniques to resolve, identify and detect their interacting partners,
      as well as to store and communicate protein information in comprehensive two
      dimensional polyacrylamide gel electrophoresis (2D PAGE) databases. Besides
      annotating the genome, these databases will offer a global approach to the study
      of gene expression both in health and disease. Here, we review the current status
      of human 2D PAGE databases that we are systematically constructing for the study
      of bladder cancer and skin ageing.

PMID- 12231221
TI  - Bioinformatics for the genomic sciences and towards systems biology. Japanese
      activities in the post-genome era.
AB  - The knowledge gleaned from genome sequencing and post-genome analyses is having a
      very significant impact on a whole range of life sciences and their applications.
      'Genome-wide analysis' is a good keyword to represent this tendency. Thanks to
      innovations in high-throughput measurement technologies and information
      technologies, genome-wide analysis is becoming available in a broad range of
      research fields from DNA sequences, gene and protein expressions, protein
      structures and interactions, to pathways or networks analysis. In fact, the
      number of research targets has increased by more than two orders in recent years
      and we should change drastically the attitude to research activities. The scope
      and speed of research activities are expanding and the field of bioinformatics is
      playing an important role. In parallel with the data-driven research approach
      that focuses on speedy handling and analyzing of the huge amount of data, a new
      approach is gradually gaining power. This is a 'model-driven research' approach,
      that incorporates biological modeling in its research framework. Computational
      simulations of biological processes play a pivotal role. By modeling and
      simulating, this approach aims at predicting and even designing the dynamic
      behaviors of complex biological systems, which is expected to make rapid progress
      in life science researches and lead to meaningful applications to various fields
      such as health care, food supply and improvement of environment. Genomic sciences
      are now advancing as great frontiers of research and applications in the 21st
      century. This article starts with surveying the general progress of
      bioinformatics (Section 1), and describes Japanese activities in bioinformatics
      (Section 2). In Section 3, I will introduce recent developments in Systems
      Biology which I think will become more important in the future.

PMID- 12231223
TI  - Effects of lesions of various brain areas on drug priming or footshock-induced
      reactivation of extinguished conditioned place preference.
AB  - We have previously shown with a model of morphine-induced conditioned place
      preference (CPP) that a brief exposure to footshock stress or a priming dose of
      morphine could reactivate drug-seeking behavior after a long drug-free period.
      The present study was designed to examine the possible role of certain brain
      areas in such a reactivation. After the rats were successfully trained with
      morphine (4 mg/kg, i.p.) through a CPP paradigm (10 sessions of daily pairing of
      morphine with one of the two compartments), different parts of nucleus accumbens
      (NAc), ventral tegmental area (VTA), and central (Ce) or lateral (La) nucleus of
      amygdala were lesioned with a DC current passing through the respective location.
      After a 9-day abstinence period, random intermittent footshock (DC square wave,
      0.5 mA, 0.5 s width, off time 10-70 s) or drug priming (morphine 0.25 mg/kg,
      s.c.) reactivated the place preference in sham lesion rats. However, the effect
      of drug priming could be completely abolished by lesions placed either at VTA, or
      the majority or shell part, but not the core of NAc. On the other hand, the
      effect of footshock stressor could be eliminated by a lesion placed at Ce but not
      La. These results suggest that, while both drug priming and footshock stress are
      effective in reactivating drug-seeking behavior, they might work through
      different neurochemical mechanisms and anatomical pathways.

PMID- 12231222
TI  - Ionic ligand interactions with the intracellular loop of the sodium-calcium
      exchanger. Modulation by ATP.
AB  - In the last decade, there has been a large increase in the study of the
      Na(+)/Ca(2+) exchanger due to its implications in physiological and
      pathophysiological processes at the cell and organ levels. Key areas of these
      studies have been molecular biology, regulation and physiology-pathophysiology of
      the exchanger. There are three main types of regulation that take place at the
      large intracellular loop of the Na(+)/Ca(2+) exchanger: (i) ionic (sodium
      inactivation, calcium regulation and proton inhibition), (ii) metabolic (ATP as
      phosphoryl group donor), and (iii) genetic (alternative splicing). This review
      analyzes the most recent data on the mutual interactions of regulatory ionic
      ligands (Ca(2+), Na(+), H(+)) and how they are secondarily modulated by MgATP,
      emphasizing the importance of the binding of Ca(2+) to its regulatory site as an
      essential requirement for the exchange function. Intracellular protons and sodium
      inhibit the Na(+)/Ca(2+) exchanger by reducing the apparent affinity of the Ca(i)
      regulatory site for Ca(2+). Although the metabolic pathways are different in the
      mammalian heart (membrane lipids) and squid nerve cells (soluble cytosolic
      regulatory protein), the final mechanism for the protective effect of MgATP is
      the same: a reduction of Na(i)(+)-H(i)(+) binding affinities facilitating the
      attachment of Ca(2+) to its regulatory site. Kinetic models, which partially
      analyzed some of these ionic and metabolic interactions, can be integrated into a
      single scheme where the Ca(i)-regulatory site plays a central role.

PMID- 12231224
TI  - Inactivation of the human brain muscarinic acetylcholine receptor by oxidative
      damage catalyzed by a low molecular weight endogenous inhibitor from Alzheimer's
      brain is prevented by pyrophosphate analogs, bioflavonoids and other
      antioxidants.
AB  - Oxidative stress has been implicated as a contributing factor to
      neurodegeneration in Alzheimer's disease. An endogenous, low molecular weight
      (LMW) inhibitor from Alzheimer's brain inactivates the human brain muscarinic
      acetylcholine receptor (mAChR). The inhibitor prevents agonist and antagonist
      binding to the mAChR as assessed by radioligand binding studies. The LMW
      endogenous inhibitor, which has components with molecular weights between 100 and
      1000 Da, requires dissolved oxygen and glutathione. Prevention of inactivation of
      the mAChR with peroxidase suggests that the LMW endogenous inhibitor generates
      peroxide. Heme, previously shown to be present in the LMW endogenous inhibitor,
      also inactivates the mAChR in the presence of peroxide. Free radical damage to
      the muscarinic receptor by the endogenous inhibitor can be prevented through the
      use of naturally occurring antioxidants including bilirubin, biliverdin,
      carnosol, myricetin and quericetin. In addition, pyrophosphate, imidodiphosphate,
      bisphosphonates and related compounds also protect the muscarinic receptor from
      free radical damage. Inactivation of the mAChR by the LMW endogenous inhibitor is
      likely to be a factor in the continual decline of Alzheimer's patients, even
      those taking acetylcholinesterase inhibitors. Natural antioxidants and
      pyrophosphate analogs may improve the effectiveness of acetylcholinesterase
      inhibitors and prove useful in the treatment and prevention of Alzheimer's
      disease since the muscarinic acetylcholine receptor is required for memory, and
      decreased cholinergic function is a critical deficit in Alzheimer's disease.

PMID- 12231225
TI  - Dorsal root rupture injury induces extension of astrocytic processes into the
      peripheral nervous system and expression of GDNF in astrocytes.
AB  - Preganglionic brachial plexus injuries fall into two categories according to the
      lesion site, root avulsion injury and root rupture injury. The latter type of
      injury involves part of the peripheral nervous system (PNS) component at the
      injured spinal cord surface. Previous investigators have used rhizotomy of
      experimental animals as a model for dorsal root rupture injury. However, the
      effect on the central nervous system (CNS)-PNS junction accompanied by the
      mechanical stress from traction force is hard to estimate in this model. The
      current study aimed to demonstrate temporal molecular alterations from the CNS
      PNS junction to the ruptured dorsal root after traction injury by
      immunohistochemical procedures. At 28 days after dorsal rupture injury, GFAP
      positive structures could be clearly identified showing rather straight lines
      from the centro-peripheral junction toward the peripheral stump in the ruptured
      dorsal root. Immunoelectron microscopy for GFAP verified GFAP IR within the
      astrocytic processes at the injured dorsal root at 28 days after dorsal rupture
      injury. Glial cell line-derived neurotrophic factor immunoreactivity (GDNF IR)
      was slightly upregulated within the Schwann cell bodies on the injured dorsal
      root at 24-48 h after rupture injury. However, GDNF IR had appeared showing a
      process-like profile on the ruptured dorsal root by 28 days, and it was closely
      related with GFAP-positive structures. In contrast, a small increase in GFAP IR
      was only detected on the proximal side on the rhizotomized dorsal root at 28 days
      after rhizotomy. A marked decrease in NF IR and S-100 IR was observed at the
      ruptured dorsal root from 7 days. On the other hand, laminin IR was strongly
      upregulated on the ruptured dorsal root from 48 h to 7 days, and was still
      evident at 28 days. We therefore conclude that the astrocytes show a unique
      ability to extend their processes toward the stump. This ability may provide a
      new medium for the study of axonal regeneration in future clinical experiments.

PMID- 12231226
TI  - Hippocampal noradrenergic responses to CRF injected into the locus coeruleus of
      unanesthetized rats.
AB  - Intracerebral administration of corticotropin-releasing factor (CRF) activates
      cerebral noradrenergic neurons. Direct infusion of CRF into the locus coeruleus
      (LC) increases norepinephrine (NE) release in the cortex and hippocampus as
      assessed by in vivo microdialysis. In a recent study using in vivo
      chronoamperometry in anesthetized rats, CRF injected into the LC increased
      apparent NE release in the hippocampus, but did so after a significant delay,
      much longer than observed following infusion of glutamate into the same site.
      Because this delay may have been an artifact of the urethane anesthesia, we
      developed a method for chronoamperometric recording from the hippocampus of
      unanesthetized rats. CRF infusion into the LC of such animals induced an increase
      in the apparent release of hippocampal NE after a mean delay of about 7 min,
      reached a peak around 16 min after CRF, and dissipated within 30 min. Thus the
      response closely resembled that previously reported in urethane-anesthetized
      rats. As in anesthetized rats, glutamate infused into the same site resulted in a
      much more rapid response (starting within 1 min and with a peak around 7 min).
      These results suggest that the urethane anesthesia does not substantially alter
      hippocampal NE release following infusion of CRF into the LC, and that the
      relatively long delay in the response is not an artifact of the anesthesia. The
      large differences in the responses to glutamate and CRF suggest that the effects
      of CRF are not exerted directly on receptors on LC neurons, and more likely
      reflect indirect actions on other cells in this region.

PMID- 12231227
TI  - Learning impairments in monkeys with combined but not separate excitotoxic
      lesions of the anterior and mediodorsal thalamic nuclei.
AB  - Clinical studies in humans and experiments in macaques suggest that damage to the
      anterior and the mediodorsal thalamus can induce a moderate amnesia, but a more
      dense impairment may result from substantial damage within the temporal lobes or
      their subcortical connections. Lesions of the anterior thalamus in macaques
      produce impairments which resemble those seen after lesions of the fornix
      mamillary pathway, which carries projections from the hippocampus to the anterior
      thalamus, while lesions of the mediodorsal thalamus, which receives inputs from
      frontal and temporal cortex, produce moderate impairments on a wider range of
      memory tasks. In the present study, we have made bilateral excitotoxic lesions of
      either the anterior or the mediodorsal thalamus, or both, in marmoset monkeys.
      Monkeys with lesions of both thalamic nuclei were severely impaired on retention
      and new learning of examples of the visuospatial conditional task, a task which
      is specifically impaired by lesions of the fornix or hippocampus. They were not
      impaired on performance of a visuovisual conditional task on which monkeys with
      hippocampal lesions are impaired, nor were they impaired on any visual
      discrimination task, including the concurrent discrimination task on which
      monkeys with temporal neocortical ablations are impaired. Monkeys with separate
      lesions of either the anterior or the mediodorsal thalamus were not impaired on
      any of these tasks. These results suggest that the mediodorsal thalamus and the
      anterior thalamus are both involved in processing the output of the hippocampal
      fornix-thalamic circuit. Dense amnesia may result from damage to circuits
      additional to the temporal lobe efferents to either the anterior or the
      mediodorsal nuclei.

PMID- 12231228
TI  - Neonatal maternal separation reduces hippocampal mossy fiber density in adult
      Long Evans rats.
AB  - Neonatal maternal separation of rat pups leads to a stable stress hyper
      responsive phenotype characterized by increased basal levels of corticotropin
      releasing factor (CRF) mRNA in the hypothalamic and extra-hypothalamic nuclei,
      increased hypothalamic CRF release, and enhanced adrenocorticotrophin hormone
      (ACTH) and corticosterone (CORT) responses to psychological stressors. Stress and
      exposure to glucocorticoids either early in life or in adulthood have been
      associated with hippocampal atrophy and impairments in learning and memory. In
      this study, male Long Evans rat pups were exposed to daily 3-h (HMS180) or 15-min
      (HMS15) periods of maternal separation on postnatal days (PND) 2-14 or normal
      animal facility rearing. Maternal separation and subsequent reunion with the dam
      resulted in elevated plasma CORT levels versus HMS15 animals at PND7, a time when
      rat pups are normally hyporesponsive to stressors and show limited pituitary
      adrenal responses. As adults, HMS180 rats exhibited elevated indices of anxiety,
      startle-induced pituitary-adrenal hyper-responsiveness, and slight, but
      significant impairment on acquisition in the Morris water maze task. In addition,
      HMS180 rats exhibited decreased mossy fiber density in the stratum oriens region
      of the hippocampus as measured by Timm's staining, but no change in volume of the
      dentate gyrus. These changes may be the result of neonatal exposure to elevated
      glucocorticoids and/or changes in other signaling systems in response to maternal
      separation. Overall the results suggest that repeated, daily, 3-h maternal
      separations during critical periods of hippocampal development can disrupt
      hippocampal cytoarchitecture in a stable manner. The resulting change in
      morphology may contribute to the subtle, but consistent learning deficit and
      overall stress hyper-responsive phenotype observed in these animals.

PMID- 12231229
TI  - Spinal cord modulation associated with isometric contractions.
AB  - OBJECTIVE: The dual-strategy hypothesis explains single-joint voluntary movement
      by dividing movements into two different strategies and suggesting that different
      excitation pulses modulate these movements. The existence of this excitation
      pulse was evaluated by quantifying magnitude and timing changes in the H-reflex
      (changes in spinal excitability) prior to a voluntary contraction. These changes
      in spinal excitability were assessed during a ballistic plantar flexion isometric
      contraction, where both the target size and force level was manipulated. METHODS
      AND MATERIALS: Subjects were seated in a modified chair with a force transducer
      placed under the metatarsal heads to measure ankle force output. Following a
      visual stimulus subjects were trained to produce a plantar flexion force of 25%
      and 50% of a maximum voluntary contraction, within target sizes of 5% and 15% of
      the selected force level. Soleus motor neuron reflex excitability was analyzed by
      measuring changes in the H/M ratio. The H-reflex was randomly elicited by tibial
      nerve stimulations at 15, 30, 45, 60, 75 and 90 ms prior to the recorded average
      soleus premotor time for each of the force and target size conditions. RESULTS: A
      two-way repeated-measures analysis of variance indicated a significant effect
      among target sizes for the time of change in spinal excitability, slope of
      facilitation (rate of rise of spinal excitability), and peak facilitation. A
      significant difference was also established between force levels for the slope
      and peak facilitation, but there was no difference with time of facilitation.
      CONCLUSIONS: These results indicate that changes in both target size and force
      level can influence slope and peak of facilitation. However, only target size
      appears to affect the time of facilitation. Results clearly support the existence
      of an excitation pulse that is regulated by the type of movement.

PMID- 12231230
TI  - Guanine and adenine nucleotidase activities in rat cerebrospinal fluid.
AB  - Adenine and guanine nucleotides have been shown to exert multiple roles in
      central and peripheral nervous systems, and the sequential breakdown of these
      nucleotides by enzymatic systems is an important step in the modulation of their
      extracellular effects. The aim of this study was to investigate whether
      nucleotide hydrolysis also occurs in the cerebrospinal fluid (CSF) of rats. CSF
      was able to hydrolyze all guanine and adenine nucleotides investigated (2.0 mM):
      GDPz.Gt;ADP=ATP=GTPz.Gt;AMP=GMP. More detailed studies with the diphosphate
      nucleotides showed that the hydrolysis of ADP and GDP was linear with incubation
      time and protein concentration. The apparent K(M) (Henry-Michaelis-Menten
      constant) and V (maximal velocity) values for ADP and GDP were 164.3+/-54.7
      microM and 12.2+/-3.8 nmol P(i)/min per mg protein, and 841.0+/-90.2 microM and
      22.8+/-8.0 nmol P(i)/min per mg protein. The sum of ADP, GDP and UDP hydrolysis
      (2.0 mM) upon individual incubations with CSF was similar to the hydrolysis
      observed when all three nucleotides were incubated together. This pattern of
      hydrolysis strongly suggests the involvement of more than one enzyme activity.
      The higher maximum activity for GDP and UDP compared to ADP is compatible with
      presence of a soluble NTDPase5.

PMID- 12231231
TI  - Mating-activated nitric oxide-producing neurons in specific brain regions in the
      female rat.
AB  - Nitric oxide (NO)-containing neurons have been localized in various parts of the
      central nervous system including the hypothalamus. NO plays an important role in
      the regulation of reproductive activities including sexual behavior and pituitary
      hormone secretion. To test the hypothesis that NO-containing neurons in specific
      brain areas may respond to the stimulus of mating and participate in integrating
      the tactile information in the hypothalamus, this study used Fos as a marker of
      neuronal activity. Proestrous rats receiving intromissions (mated group) from
      males or mounts-without-intromission (mounted group) were sacrificed along with
      rats taken directly from their home cage (control group) 90 min after the
      beginning of mating or mounting. NOergic neurons were labeled by histochemical
      reaction for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d).
      The presence of activated NO-producing (double-stained NADPH-d/Fos) neurons was
      quantitatively assessed in several brain areas before and after mating. The
      results showed that mating-with-intromissions induced a significant increase in
      the percentage of NADPH-d/Fos colabeled neurons in the medial preoptic area
      (mPOA) and the magnocellular component of the paraventricular nucleus (PVNm)
      compared to mounts-without-intromission or control treatment. Both mating and
      mounting induced Fos expression in NADPH-d-positive cells in the ventromedial
      nucleus of hypothalamus (VMN). In contrast, the expression of Fos in the NADPH-d
      positive neurons in the supraoptic nucleus (SON) and the parvocellular portion of
      the paraventricular nucleus (PVNp) was not influenced by either mating or
      mounting although abundant NO-containing neurons were found in the two brain
      areas. The second experiment of the study examined whether NOergic neurons in
      these brain areas are influenced directly by estrogen by determining the number
      of NADPH-d-positive neurons that contained the estrogen receptor alpha (ERalpha),
      the classical ER. Double labeled NADPH-d/ERalpha neurons were observed in several
      brain areas including the mPOA and VMN while few, if any, NADPH-d-positive
      neurons in the SON, PVNm or PVNp contained ERalpha. The results suggest that the
      activated NOergic neurons in these brain areas may be involved in processing and
      integrating the mating stimulus. Further investigation is required to determine
      the physiological role of the mating-activated NOergic activity in specific
      mating-induced changes in reproductive neuroendocrinology.

PMID- 12231232
TI  - The striatum as a target for anti-rigor effects of an antagonist of mGluR1, but
      not an agonist of group II metabotropic glutamate receptors.
AB  - The aim of the present study was to find out whether the metabotropic receptor 1
      (mGluR1) and group II mGluRs, localized in the striatum, are involved in
      antiparkinsonian-like effects in rats. Haloperidol (1 mg/kg ip) induced
      parkinsonian-like muscle rigidity, measured as an increased resistance of a rat's
      hind foot to passive flexion and extension at the ankle joint. (RS)-1-aminoindan
      1,5-dicarboxylic acid (AIDA; 0.5-15 microg/0.5 microl), a potent and selective
      mGluR1 antagonist, or (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC;
      7.5-15 microg/0.5 microl), a selective group II agonist, was injected bilaterally
      into the striatum of haloperidol-treated animals. AIDA in doses of 7.5-15
      microg/0.5 microl diminished the haloperidol-induced muscle rigidity. In
      contrast, 2R,4R-APDC injections were ineffective. The present results may suggest
      that the blockade of striatal mGluR1, but not the stimulation of group II mGluRs,
      may ameliorate parkinsonian muscle rigidity.

PMID- 12231233
TI  - Effects of arachidonic acid on sodium currents in rat dorsal root ganglion
      neurons.
AB  - The effects of arachidonic acid on tetrodotoxin-sensitive (TTX-S) and
      tetrodotoxin-resistant (TTX-R) sodium currents in rat dorsal root ganglion
      neurons were assessed using the whole-cell patch-clamp method. Both sodium
      currents were modulated in a similar way by extracellular application of
      arachidonic acid. Arachidonic acid increased the currents at lower depolarizing
      potentials, while it suppressed the currents at higher depolarizing potentials
      and at less negative holding potentials. These effects were due to the shifts of
      both the conductance-voltage curve and the steady-state inactivation curve in the
      hyperpolarizing direction. Indomethacin, a cyclooxygenase inhibitor, suppressed
      the arachidonic acid-induced shift of the conductance-voltage curve but not that
      of the steady-state inactivation curve. 5,8,11,14-Eicosatetraynoic acid, a non
      metabolizable arachidonic acid analog, failed to shift the conductance-voltage
      curve but still produced the shift of the steady-state inactivation curve. Thus
      it is assumed that the effect of arachidonic acid on the sodium channel
      activation is caused by the metabolite(s) of arachidonic acid. However, the
      effect on the steady-state sodium channel inactivation is exerted by arachidonic
      acid itself. It is suggested that arachidonic acid, by modulating sodium
      currents, may alter the excitability of sensory neurons depending on the resting
      membrane potential.

PMID- 12231234
TI  - Pilocarpine-induced seizure-like activity with increased BNDF and neuropeptide Y
      expression in organotypic hippocampal slice cultures.
AB  - Organotypic hippocampal slice cultures were treated with the muscarinic agonist
      pilocarpine to study induced seizure-like activity and changes in neurotrophin
      and neuropeptide expression. For establishment of a seizure-inducing protocol, 2
      week-old cultures derived from 6-8-day-old rats were exposed to 0.1 mM to 5 mM of
      pilocarpine for 4 h to 7 days. Other cultures were treated with pilocarpine for 7
      days and left for 7-14 days in normal medium. Age-matched, non-treated cultures
      served as controls. Intracellular recordings from CA1 pyramidal cells revealed
      increased spontaneous activity in 31 of 35 cultures superfused with 0.1 or 5 mM
      pilocarpine. Epileptiform discharges were recorded in 17 of the 31 cultures, and
      19 displayed frequencies specifically in the 6-12-Hz (Theta rhythm) range when
      superfused with pilocarpine. The pilocarpine effect was blocked by simultaneous
      superfusion with the muscarinic receptor antagonist atropine (100 microM).
      Regardless of dose and exposure time, the pilocarpine treatment induced very
      limited neuronal cell death, recorded as cellular propidium iodide uptake.
      Cultures exposed to 5 mM pilocarpine for up to 7 days displayed increased BDNF
      expression when analyzed by Western blot and ELISA. This BDNF increase correlated
      with increased neuropeptide Y immunoreactivity, known to accompany seizure
      activity. Addition of BDNF (200 ng/ml) to otherwise untreated cultures also
      upregulated NPY expression. The pilocarpine-induced seizure-like activity in
      hippocampal slice cultures, with concomitant increase in BDNF and NPY expression,
      is compared with in vivo observations and discussed in terms of the potential use
      of the easily accessible slice cultures in experimental seizure research.

PMID- 12231235
TI  - Effects of cue exposure on brain glucose utilization 8 days after repeated
      cocaine administration.
AB  - Relapse to cocaine use may involve exposure to cocaine-associated environmental
      cues. The present experiment tested the hypothesis that basal local cerebral
      metabolic rate for glucose (LCMR(glu)), as measured by the 2-deoxy-D-[l
      (14)C]glucose (2-DG) autoradiography, would change in the presence of cocaine
      conditioned cues at 8 days after the last of seven daily cocaine injections (30
      mg/kg). This dose regimen results in sensitization to the locomotor effects of
      cocaine. Cocaine was administered to two groups of rats while saline was
      administered to a third. In the conditioned group, the rats were placed into the
      2-DG experimental chamber immediately after cocaine injection. Rats in the non
      conditioned group were placed into their home cage after cocaine administration.
      A control group received only saline. The 2-DG experiment was conducted in non
      drugged animals 8 days after treatment completion. The interaction between
      treatment status and brain region was significant. Mean basal LCMR(glu) was
      significantly lower in 12 brain regions in the conditioned group as compared to
      the control group, but was significantly lower in only four areas in the non
      conditioned group. Regions in which there were significant changes in the
      conditioned group included the basolateral amygdala, subiculum, medial thalamus,
      lateral habenula and the substantia nigra pars compacta. LCMR(glu) was
      significantly reduced in the ventrolateral orbital cortex and rostral nucleus
      accumbens in both experimental groups. These findings indicate that repeated
      cocaine administration can cause protracted decreases in basal LCMR(glu),
      decreases that are more widespread in the brain during exposure to cocaine
      associated cues.

PMID- 12231236
TI  - Effects of NMDA antagonist MK-801 on radial maze performance in Zucker rats.
AB  - We examined the participation of the NMDA receptor in the histaminergic system
      using radial maze performance in Zucker rats. Although pyrilamine caused a
      significant effect on spatial memory deficit in lean rats, no significant spatial
      memory deficit was observed in obese rats. On the other hand, MK-801 caused
      significant spatial memory deficits in obese rats in comparison with lean rats.
      These results indicate that the histaminergic neuron is not closely related with
      the radial maze performance in obese rats. In addition, the potent effect of MK
      801 observed in obese rats compared with lean rats may be responsible for the
      activation of NMDA receptors in obese rats.

PMID- 12231237
TI  - Leptin transport across the blood-brain barrier of the Koletsky rat is not
      mediated by a product of the leptin receptor gene.
AB  - Obesity in humans is thought to be caused by a resistance to leptin. Currently,
      the evidence suggests that this resistance is caused by an impaired transport of
      leptin across the blood-brain barrier (BBB). It has been assumed that the short
      form of the leptin receptor, which is a splice variant of the gene which produces
      all known leptin receptors, is the leptin transporter, but evidence for this is
      mixed. The Koletsky rat model should provide a clear answer as to whether
      transport is dependent on leptin receptors as it does not express any functional
      receptors. The transport of intravenous leptin across the BBB of the Koletsky rat
      has been found to be greatly reduced, but evidence for a residual of transport
      makes it unclear whether the transporter is essentially absent or simply
      saturated by the high levels of leptin in the serum. Here we used the brain
      perfusion method to negate the influence of serum levels. We found that, whereas
      no transport of intravenous leptin occurred in the obese Koletsky, the rate of
      transport was no different from controls when brain perfusion was used. Leptin
      was transported completely across the BBB, was saturable, and had the same
      distribution among brain regions as previously found in normal weight mice
      (highest transport into the hippocampus and hypothalamus, lowest in the frontal
      cortex). We conclude that a leptin transporter and possibly its gene have yet to
      be identified and that the short form likely plays a role in the modulation of
      transport activity.

PMID- 12231238
TI  - The effects of chronic ethanol consumption on neurotrophins and their receptors
      in the rat hippocampus and basal forebrain.
AB  - Damage to the basal forebrain frequently results in deficits in learning and
      memory. Mnenonic dysfunction also occurs following prolonged ethanol consumption
      in humans and in animal models of chronic ethanol intake, accompanied by specific
      abnormalities in synaptic transmission between the basal forebrain and
      hippocampus. The integrity of at least some of the reciprocal neuronal
      connections between these brain regions is influenced by target-derived
      neurotrophic factors. We used a semiquantitative reverse transcription polymerase
      chain reaction technique to measure the messenger RNA for neurotrophins BDNF and
      NGF, and for their receptors trkB, trkA, and the low affinity receptor, p75(NTR)
      in the hippocampus and basal forebrain of rats after 28 weeks of alcohol
      consumption without malnutrition. This chronic ethanol treatment (CET) resulted
      in a marked and selective reduction in basal forebrain trkA mRNA. Western
      blotting revealed a similar reduction of basal forebrain trkA protein. CET
      effects on basal forebrain trkA may reflect impaired NGF signaling that could
      compromise septohippocampal synaptic connections, cholinergic differentiation,
      and emergent functional abilities dependent on these properties.

PMID- 12231239
TI  - Regional distribution of protein and activity of the nitric oxide receptor,
      soluble guanylyl cyclase, in rat brain suggests multiple mechanisms of
      regulation.
AB  - Nitric oxide (NO) is an unconventional neuromodulator that signals by
      intercellular diffusion. Its effects are often mediated by activation of its
      cytosolic receptor, the hemoprotein soluble guanylyl cyclase (sGC). Regional
      distribution of heterodimeric (alpha/beta) sGC at both the activity and protein
      level and its regulation are still unclear. Here, sGC was analyzed in rat brain
      by Western blot and NO donor-stimulated cyclic GMP accumulation. sGCalpha(1) and
      sGCbeta(1) immunoreactive protein signals strongly correlated with each other.
      However, V(max) values depended on the type of NO donor used. Sodium
      nitroprusside, the most widely used compound and formally an NO(+) donor, was up
      to 20-fold less effective in stimulating sGC activity than the NO donor
      diethylamine NONOate. In contrast to the rather even distribution of sGC proteins
      and SNP-stimulated cGMP accumulation in various regions of rat brain,
      diethylamine NONOate-stimulated sGC activity varied up to 8-fold between the
      different brain regions tested. In conclusion, we show that expression of both
      sGCalpha(1) and sGCbeta(1) subunits is tightly coregulated in rat brain, while
      yet unknown additional mechanisms affect the V(max) of sGC.

PMID- 12231240
TI  - The role of the external lateral parabrachial subnucleus in flavor preferences
      induced by predigested food administered intragastrically.
AB  - A study was undertaken of the role of the external lateral parabrachial
      subnucleus (PBNLe) in flavor preferences induced by the intragastric
      administration of predigested/cephalic food. These preferences were developed
      using two different learning procedures, concurrent and sequential. In the
      concurrent procedure, two different-flavored stimuli were presented at the same
      time: one stimulus was paired with the simultaneous intragastric administration
      of partially digested food and the other with physiological saline. In the
      sequential learning procedure, the two stimuli were presented at alternate
      sessions. The results showed that PBNLe lesions blocked acquisition of concurrent
      learning but had no effect on the sequential procedure. In the latter case, both
      lesioned and control animals showed a strong preference for the gustatory
      stimulus paired with partially digested food. These results are interpreted in
      terms of a dual neurobiological system involved in the rewarding effects of
      visceral signals.

PMID- 12231241
TI  - Sensitized Fos expression in subterritories of the rat medial prefrontal cortex
      and nucleus accumbens following amphetamine sensitization as revealed by
      stereology.
AB  - Behavioral sensitization to the locomotor activating effects of amphetamine
      refers to the progressive, long lasting increase in locomotor activity that
      occurs with repeated injections. This phenomenon is thought to result from
      neuroadaptations occurring in the projection fields of mesocorticolimbic
      dopaminergic neurons. In the present study, we investigated the effects of
      amphetamine sensitization on Fos immunoreactivity (Fos-IR) in subterritories of
      the nucleus accumbens (core and shell) and medial prefrontal cortex (mPFC; dorsal
      and ventral) using stereology. Rats received five daily injections of amphetamine
      (1.5 mg/kg, i.p.) or saline. Behavioral sensitization was measured 48 h following
      the last injection, in response to a challenge injection of 1.5 mg/kg
      amphetamine. Sensitized rats showed a greater enhancement of locomotor activity
      upon drug challenge compared with their saline counterparts. Densities of Fos
      positive nuclei were enhanced more in the dorsal than the ventral mPFC
      subterritory, whereas in the nucleus accumbens, densities of Fos-positive nuclei
      were increased more in the core than the shell of amphetamine-sensitized rats
      compared to controls. These results represent, to our knowledge, the first
      published report using stereological methods to quantify Fos-IR in the brain and
      suggest functional specialization of cortical and limbic regions in the
      expression of behavioral sensitization to amphetamine.

PMID- 12231242
TI  - Nerve growth factor alters p75 neurotrophin receptor-induced effects in mouse
      facial motoneurons following axotomy.
AB  - The p75 neurotrophin receptor (p75(NTR)) has been implicated as being detrimental
      for cell survival in facial motoneurons following injury. Although facial
      motoneurons do not respond to nerve growth factor (NGF) under normal
      circumstances, this study shows that NGF can interfere with p75(NTR)-mediated
      cell survival effects on motoneurons following injury. Twenty-five days following
      injury, the proportion of surviving axotomized neurons in NGF/p75(+/+) mice,
      which overexpress NGF, was significantly higher compared to wild-type mice, while
      NGF/p75(-/-) mice, which overexpress NGF but carry two mutated alleles for
      p75(NTR), had fewer neurons compared to wild-type and p75(-/-) mice, which carry
      two mutated alleles for p75(NTR), resulting in a lack of functional expression of
      this receptor. Sympathetic axons sprouted into the axotomized facial nucleus of
      both NGF/p75(+/+) and NGF/p75(-/-) following injury, due to transgene expression
      of NGF in reactive astrocytes. Removal of these sympathetic axons enhanced the
      number of surviving axotomized neurons in NGF/p75(-/-) mice but not in
      NGF/p75(+/+) mice. Although motoneurons do not express trkA and should therefore
      be unresponsive to NGF, our results reveal that NGF can influence p75-mediated
      motoneuron survival following axotomy.

PMID- 12231243
TI  - The distribution of fos immunoreactivity in rat brain following freezing and
      escape responses elicited by electrical stimulation of the inferior colliculus.
AB  - Several sources of evidence indicate that the inferior colliculus also integrates
      acoustic information of an aversive nature besides its well-known role as a relay
      station for auditory pathways. Gradual increases of the electrical stimulation of
      this structure cause in a hierarchical manner alertness, freezing and escape
      behaviors. Independent groups of animals implanted with bipolar electrodes into
      the inferior colliculus received electrical stimulation at one of these aversive
      thresholds. Control animals were submitted to the same procedure but no current
      was applied. Next, analysis of Fos protein expression was used to map brain areas
      activated by the inferior colliculus stimulation at each aversive threshold and
      in the controls. Whereas alertness elicited by stimulation of the inferior
      colliculus did not cause any significant labeling in any structure studied in
      relation to the respective control, electrical stimulation applied at the
      freezing threshold increased Fos-like immunoreactivity in the central amygdaloid
      nucleus and entorhinal cortex. In contrast, escape response enhanced Fos-like
      immunoreactivity in the nucleus cuneiform and the dorsal periaqueductal gray
      matter of the mesencephalon. This evidence supports the notion that freezing and
      escape behaviors induced by electrical stimulation of the inferior colliculus
      activate different neural circuitries in the brain. Both defensive behaviors
      caused significant expression of c-fos in the frontal cortex, hippocampus and
      basolateral amygdaloid nucleus. This indistinct pattern of c-fos distribution may
      indicate a more general role for these structures in the modulation of fear
      related behaviors. Therefore, the present data bring support to the notion that
      amygdala, dorsal hippocampus, entorhinal cortex, frontal cortex, dorsal
      periaqueductal gray matter and cuneiform nucleus altogether play a role in the
      integration of aversive states generated at the level of the inferior colliculus.

PMID- 12231244
TI  - Effect of nitric oxide on release of glutamate in the subretrofacial nucleus
      (SRF) during the exercise pressor reflex in cats.
AB  - The subretrofacial nucleus (SRF) has been known to play a crucial role in the
      expression of the exercise pressor reflex. Previously, we have reported that the
      release of glutamate (Glu) in the SRF was increased during muscle contraction in
      anesthetized cats. In this study, static muscle contraction of the triceps surae
      for 4 min was induced by electrical stimulation of L7 and S1 ventral roots.
      Endogenous release of Glu and citrulline (Cit) from the SRF was recovered by
      microdialysis and measured by HPLC. The microdialysis probes were also used to
      deliver L-arginine and L-NAME to test the effect of nitric oxide (NO) on release
      of Glu in the SRF and on the cardiovascular responses during muscle contraction.
      During control, muscle contraction significantly increased mean arterial pressure
      (MAP) from 98+/-8 to 151+/-9 mmHg, and the extracellular concentration of Glu
      from 610+/-120 to 1280+/-290 nM. Dialyzing 2 mM L-arginine into the SRF increased
      basal Cit concentration from 260+/-50 to 760+/-210 nM (P<0.05). During
      contraction after L-arginine, the increases in MAP and Glu concentration were
      significantly attenuated (86+/-3-124+/-6 mmHg and 300+/-60-460+/-100 nM,
      respectively). Dialysis of 0.5 mM L-NAME into the SRF decreased Cit concentration
      from 340+/-40 to 180+/-20 nM (P<0.05). During contraction after dialyzing L-NAME,
      the increases in MAP and Glu concentration were significantly potentiated (93+/-6
      154+/-9 mmHg and 520+/-80-1290+/-380 nM, respectively). These results suggest
      that endogenous NO modulates the cardiovascular responses to static muscle
      contraction by affecting the release of Glu in the SRF.

PMID- 12231245
TI  - Phosphorylation of c-Cbl protooncogene product following ethanol administration
      in rat cerebellum: possible involvement of Fyn kinase.
AB  - We have previously shown that ethanol administration results in tyrosine
      phosphorylation of the 130 kDa protein in rat brain, and identified the protein
      as Cas, the crk-associated src substrate. In the present study, we demonstrate
      that Cbl of a 120 kDa protein is also tyrosine-phosphorylated in the cerebellum
      in response to ethanol administration. We also investigated whether Fyn kinase
      was involved in ethanol-induced Cbl phosphorylation. Immunoprecipitation
      experiments showed that the amount of coimmunoprecipitated Fyn kinase with an
      anti-Cbl antibody increased in extracts from ethanol-administered rats compared
      to those from saline-administered rats. Exogenous Fyn kinase was shown to
      phosphorylate on tyrosine residue(s) of Cbl from the cerebellum in vitro.
      Furthermore, Fyn kinase and Cbl were demonstrated immunohistochemically to be
      coexpressed in white matter in the cerebellum. These findings indicate that Cbl
      is tyrosine-phosphorylated in rat cerebellum in response to ethanol
      administration, and also raise the possibility that Fyn kinase may be involved in
      the process.

PMID- 12231246
TI  - Vole retina is a target for gonadotropin-releasing hormone.
AB  - Gonadotropin-releasing hormone (GnRH) projections from the terminal nerve to the
      retina are common in fish, but have not been reported in mammals. However, GnRH
      fibers have been seen previously in the optic nerves (but not retinas) of rats
      and monkeys. Using prairie voles, we tested the hypotheses that (1) GnRH
      immunoreactive (-ir) neurons project into the optic nerve and (2) the retina
      expresses GnRH receptor mRNA as determined by reverse transcription-polymerase
      chain reaction (RT-PCR) combined with Southern blotting. In both adult and
      postnatal-day-2 voles, GnRH-ir fibers were observed within the optic nerve. In
      adult voles, GnRH-ir fibers projected only a short distance into the optic nerve
      compared with the much longer length of projections in neonates. Fibers
      immunoreactive for GnRH were not seen in the retinas of neonates or adults.
      However, RT-PCR-Southern blotting demonstrated GnRH receptor expression in the
      retina of adult voles. This study supports the hypothesis that GnRH has the
      potential of modulating visual processing in the retina of mammals.

PMID- 12231247
TI  - Attenuation of zinc-induced intracellular dysfunction and neurotoxicity by a
      synthetic superoxide dismutase/catalase mimetic, in cultured cortical neurons.
AB  - Excessive extracellular zinc may contribute to neuronal cell death following
      ischemia and seizures, although the mechanisms mediating zinc-induced cell death
      remain largely unknown. In this study, we examined potential cellular and
      molecular mechanisms associated with zinc neurotoxicity and determined the
      neuroprotective effects of the superoxide dismutase (SOD)/catalase mimetic, EUK
      134. Cortical neuron cultures exposed to zinc for 24 h exhibited concentration
      dependent increases in lactate dehydrogenase (LDH) release and number of
      apoptotic cell bodies. Both effects were prevented by treatment with EUK-134.
      Zinc exposure resulted in increased release of cytochrome c from the mitochondria
      into the cytosol. Treatment with EUK-134 blocked this parameter of mitochondrial
      dysfunction. Exposure of cultures to zinc for 4 h produced an elevation of
      reactive oxygen species (ROS) as determined by increased 2,7-dichlorofluorescein
      (DCF) fluorescence, which was followed by an increase in lipid peroxidation. EUK
      134 completely attenuated ROS production and subsequent oxidative damage.
      Finally, zinc exposure activated NF-kappaB, an effect also prevented by EUK-134.
      These data indicate that multiple cellular and molecular mechanisms are involved
      in zinc neurotoxicity. As all these mechanisms appear to be sensitive to
      treatment with EUK-134, our data suggest that oxidative stress occurs early in
      the cascade of events triggered by zinc.

PMID- 12231248
TI  - The effects of unilateral removal of the cerebellar hemispheres on motor
      functions and weight gain in rats.
AB  - Left or right unilateral removal of a cerebellar hemisphere resulted in a high
      mortality rate caused by anorexia, not previously seen in cerebellectomized
      animals. The reduced post-surgical gain in body weight may be explained by
      oropharyngeal dyspraxia or a loss in appetite. However, the growth rate of the
      surviving animals was similar to that of controls. After unilateral damage of the
      cerebellum, deficits were observed in motor coordination tasks, such as the
      rotorod, the hole-board, and the stationary beam, and the left hemisphere group
      fell from a suspended wire sooner than controls. The motor deficits were more
      pronounced after left as opposed to right cerebellar damage on the rotorod,
      implying a certain degree of functional lateralization for this test.

PMID- 12231249
TI  - Effects of temporary deafferentation on raccoon post-synaptic dorsal column
      neurons.
AB  - The effects of temporary deafferentation were studied in 54 post-synaptic dorsal
      column (PSDC) neurons in the cervical spinal cord of the raccoon. Deafferentation
      was induced by the injection of lidocaine into the base of the digit containing
      the receptive field of the neuron. These neurons all had receptive fields on a
      single digit of the forepaw and in no case did a new receptive field appear
      following lidocaine injection. High intensity electrical stimulation of an off
      focus digit (adjacent to the one with the receptive field) produced responses in
      92% of the neurons prior to lidocaine injection. The strength of these off-focus
      responses was not increased by deafferentation of the on-focus digit, as might be
      expected if they were being suppressed by the major input; rather it was
      decreased. These results argue against a convergence of multi-digit inputs onto
      these PSDC neurons that is masked under normal circumstances. As previously
      described for neurons in the cuneate nucleus, deafferentation produced a
      significant decrease in the spontaneous activity of PSDC neurons, indicating that
      they receive a tonic excitatory input from the periphery. The importance of these
      results in understanding the starting point for injury-induced reorganization is
      discussed.

PMID- 12231250
TI  - Evidence for different exocytosis pathways in dendritic and terminal dopamine
      release in vivo.
AB  - Although dendritic release was first proposed in the 1970s, the mechanism of
      release is still subject to debate. We have used in vivo microdialysis to study
      the acute effects of botulinum toxin A, B and tetanus toxin injected in the
      substantia nigra or striatum of freely moving rats. Spontaneous and evoked
      dopamine release decreased in both regions after treatment with the SNAP-25
      (synaptosome-associated protein of 25 kDa) cleaving protease botulinum toxin A
      (1000 mouse lethal doses, MLD). Tetanus toxin (4000 MLD) did not significantly
      change spontaneous or evoked dopamine release in striatum or in the substantia
      nigra. Another synaptobrevin cleaving protease, botulinum toxin B, inhibited
      release in the striatum by 55% but did not affect dopamine release when injected
      in the substantia nigra. The results indicate that both terminal and
      somatodendritic dopamine release need intact SNAP-25 to occur, but
      somatodendritic dopamine release in contrast to terminal release depends on a
      botulinum toxin B resistant pathway.

PMID- 12231252
TI  - Microinjection of orexin into the rat nucleus tractus solitarius causes increases
      in blood pressure.
AB  - Orexin A (OX-A) and orexin B (OX-B), also known as hypocretin-1 and hypocretin-2,
      have been suggested to play a role cardiovascular control. The nucleus tractus
      solitarius (NTS), located in the dorsal medulla plays an essential role in neural
      control of the cardiovascular system. Orexin-immunoreactive axons have been
      demonstrated within this nucleus suggesting that NTS may be a site through which
      OX acts to influence cardiovascular control. We report here that microinjection
      of OX-A into the NTS of urethane anesthetized rats causes increases in blood
      pressure (10(-9) M, mean AUC=607.1+/-65.65 mmHg s, n=5) and heart rate (10(-9) M,
      mean AUC=16.15+/-3.3 beats, n=5) which returns to baseline within 90 s. We show
      that these effects are dose related and site specific. Microinjection of OX-B
      into NTS elicited similar increases in BP (mean AUC=680.8+/-128.5 mmHg s, n=4) to
      that of OX-A suggesting specific actions at the OX(2)R receptor. These
      observations support the conclusion that orexins act as chemical messengers in
      the NTS likely influencing the excitability of cardiovascular neurons in this
      region and thus regulating global cardiovascular function.

PMID- 12231251
TI  - Lipophilic fraction of Panax ginseng induces neuronal differentiation of PC12
      cells and promotes neuronal survival of rat cortical neurons by protein kinase C
      dependent manner.
AB  - Panax ginseng is a traditional Chinese herb with a wide range of therapeutic
      benefits. Recent studies focusing on its effect on the central nervous system
      have revealed that ginseng has neurotrophic effects including differentiation of
      neurons. However, most studies involve use of the water-soluble fraction called
      saponin, and little is known about the effect of the lipophilic fraction. In the
      present study, we have shown that the lipophilic fraction of ginseng at a
      concentration of between 0.1 and 50 microg/ml can induce neurite outgrowth of
      PC12 cells in a dose-dependent manner. Nearly all cells showed morphological
      differentiation in response to the lipophilic fraction. This morphological
      differentiation of PC12 cells appeared to be similar to that of NGF. The
      lipophilic fraction of ginseng also induced neurite extension and promoted
      survival of rat cortical neurons at a concentration of between 0.025 and 1
      microg/ml. These neurotrophic effects on PC12 cells and cortical neurons were not
      inhibited by K252b, which selectively blocks neurotrophin actions by inhibiting
      trk-type receptor tyrosine phosphorylation. This suggests that trks do not
      participate in the neurotrophic action of the lipophilic fraction. However, the
      effects were completely attenuated by sphingosine, polymyxin B or staurosporin,
      known inhibitors of protein kinase C (PKC) and calmodulin-dependent kinases. Our
      results suggest that the lipophilic fraction of ginseng exerts its neurotrophic
      effects via PKC-dependent pathways.

PMID- 12231253
TI  - Effects of LF 16-0687 Ms, a bradykinin B(2) receptor antagonist, on brain edema
      formation and tissue damage in a rat model of temporary focal cerebral ischemia.
AB  - Bradykinin, an endogenous nonapeptide produced by activation of the kallikrein
      kinin system, promotes neuronal tissue damage as well as disturbances in blood
      brain barrier function through activation of B(2) receptors. LF 16-0687 Ms, a non
      peptide competitive bradykinin B(2) receptor antagonist, was recently found to
      decrease brain swelling in various models of traumatic brain injury. We have
      investigated the influence of LF 16-0687 Ms on the edema formation, neurological
      outcome, and infarct size in temporary focal cerebral ischemia in rats. Sprague
      Dawley rats were subjected to MCA occlusion for 90 min by an intraluminal
      filament. Local CBF was bilaterally recorded by laser Doppler flowmetry. Study I:
      animals were assigned to one of three treatment arms (n=11 each): (a) vehicle,
      (b) LF 16-0687 Ms (12.0 mg/kg per day), or (c) LF 16-0687 Ms (36.0 mg/kg per day)
      given repetitively s.c. over 3 days. The neurological recovery was examined
      daily. The infarct volume was assessed histologically 7 days after ischemia.
      Study II: brain swelling and bilateral hemispheric water content were determined
      at 48 h post ischemia in eight rats, subjected to the low dose regimen as
      described above, and in eight vehicle-treated control animals. All treated
      animals showed tendency to exhibit improved neurological recovery throughout the
      observation period as compared to the vehicle-treated controls, while this
      improvement was only significant within the low dose group from postischemic days
      3 to 4. Low dose LF 16-0687 Ms significantly attenuated the total and cortical
      infarct volume by 50 and 80%, respectively. Furthermore, postischemic swelling (
      62%) and increase in water content of the infarcted brain hemisphere (-60.5%) was
      significantly inhibited. The present findings provide strong evidence for an
      involvement of bradykinin-mediated secondary brain damage following from focal
      cerebral ischemia. Accordingly, specific inhibition of bradykinin B(2) receptors
      by LF 16-0687 Ms attenuated postischemic brain swelling, improved the functional
      neurological recovery, and limited ischemic tissue damage, raising its potential
      for clinical evaluation in patients with acute stroke.

PMID- 12231254
TI  - Asymmetrical distribution of the Schaffer projections within the apical dendrites
      of hippocampal field CA1.
AB  - Continuous current source densities were calculated in two dimensions (proximo
      distal vs. medio-lateral) from slices of hippocampal field CA1 placed on a 64
      electrode array in the presence of GABA blockers. The synaptic sink generated by
      stimulation of the Schaffer-commissural fibers spread across the extent of field
      CA1 within the same sublamina of the stratum radiatum as the stimulation
      electrode. The size and shape of the current sink varied according to the proximo
      distal position of the stimulation site. Sinks generated by stimulation close to
      the cell body layer were more compact when compared to those produced by
      stimulation near the top of stratum radiatum which were broad and skewed in the
      proximal direction. These distributions were obtained with stimulation at either
      the CA3 or the subicular border of CA1. Induction of LTP increased the intensity
      of the current field but did not notably affect its distribution. It is concluded
      that (1) axons remain at the same proximo-distal level as they traverse stratum
      radiatum of CA1 and (2) generate proximally directed collaterals. Because of
      this, fibers that enter CA1 stratum radiatum immediately above the pyramidal cell
      bodies form compact synaptic fields while those entering CA1 at the top of the
      lamina form much broader and asymmetrical distributed fields.

PMID- 12231255
TI  - Expression and localization of cytochrome P450(11beta,aldo) mRNA in the frog
      brain.
AB  - The present study is focused on biosynthesis of adrenal steroids in the frog
      brain. Employing RT-PCR method using total RNA from the adult Rana nigromaculata
      brain, we isolated a 419-bp fragment of cDNA encoding cytochrome
      P450(11beta,aldo), which catalyzes the final step of biosynthesis of the frog
      adrenal steroids, corticosterone and aldosterone. The deduced amino acid sequence
      of R. nigromaculata brain cytochrome P450(11beta,aldo) shared a high homology
      (88.8%) with that of R. catesbeiana adrenal cytochrome P450(11beta,aldo).
      Southern blot analysis of the RT-PCR product confirmed the P450(11beta,aldo)
      transcription in the frog brain without a clear-cut sex difference. Then, we
      analyzed the P450(11beta,aldo) mRNA expression in different brain regions of the
      adult frog by RT-PCR method. The P450(11beta,aldo) gene was transcribed in the
      telencephalon, diencephalon, midbrain, and cerebellum. The transcript level of
      the frog beta-actin gene was relatively constant in all the frog samples
      examined. In situ hybridization analysis showed that the P450(11beta,aldo) gene
      was transcribed abundantly in the cells throughout the frog brain, such as the
      pallium mediale in the telencephalon, the nucleus preopticus in the diencephalon,
      the stratum griseum superficiale tecti in the midbrain, and Purkinje cells in the
      cerebellum. These results taken together suggest that the frog brain synthesizes
      adrenal steroids, such as corticosterone and aldosterone.

PMID- 12231256
TI  - Aging alters light- and PACAP-induced cAMP accumulation in the suprachiasmatic
      nucleus of female rats.
AB  - Light-induced release of pituitary adenylate cyclase activating peptide (PACAP)
      from retinal ganglion cells can modulate the phase-shifting effects of light
      though a cAMP-mediated mechanism in neurons of the suprachiasmatic nucleus (SCN).
      Since older animals (12 months or older) show a reduced behavioral and cellular
      response to light presented during the early portion of the dark phase of the
      cycle, we hypothesized that aging may alter the ability of PACAP and cAMP to
      modulate the phase shifting effects of light. In Expt. 1, we examined basal and
      light-induced cAMP accumulation at zeitgeber time 14 (ZT14 where ZT0 is the time
      of lights on). Light exposure resulted in a significant increase in cAMP
      accumulation in SCN tissue collected from young, but not middle-aged animals. The
      failure to see an increase in cAMP accumulation in the SCN of middle-aged animals
      may be related to the fact that basal levels of cAMP were elevated in the SCN of
      these animals at ZT14. In Expt. 2, we used an in vitro slice preparation of the
      SCN to determine if aging altered the ability of PACAP to stimulate cAMP
      accumulation in the SCN at ZT14. PACAP stimulated cAMP in the SCN of both young
      and middle-aged animals. However, PACAP-induced cAMP accumulation was lower in
      the SCN of middle-aged animals. Based on these results, we conclude that age
      related changes in the responsiveness of the SCN to light input are due to: (1)
      changes in other input pathways capable of modulating cAMP, and (2) decreases in
      PACAP receptors in SCN neurons.

PMID- 12231257
TI  - TASK-1, TASK-2, TASK-3 and TRAAK immunoreactivities in the rat carotid body.
AB  - In the present study, we investigated the immunohistochemical localization of two
      pore K(+)-channels TASK-1, TASK-2, TASK-3 and TRAAK in the rat carotid body. Type
      I cells were positive for TASK-1, TASK-2, TASK-3 and TRAAK. Intrinsic nerve cell
      bodies were also strongly positive for TASK-1, TASK-2 and TRAAK, but negative for
      TASK-3. In addition, some type II cells, Schwann cells in the nerve bundles and
      fibroblast between type I cell clusters were also immunostained for TASK-1.
      Smooth muscle cells of the carotid body artery were intensely positive for TASK
      3. Our results indicate that TASK-1 immunoreactivity was ubiquitously distributed
      in many cell types and immunoreactivities for TASK-2, TASK-3 and TRAAK were cell
      type specific distribution patterns in the rat carotid body.

PMID- 12231258
TI  - Estrogen induces a rapid increase of calcium-calmodulin-dependent protein kinase
      II activity in the hippocampus.
AB  - Molecular genetics experiments using gene targeting and transgenic technology
      demonstrated the importance of alpha-calcium-calmodulin-dependent protein kinase
      II (alphaCaMKII) in long-term potentiation (LTP) and memory. Little information
      is available though on how CaMKII activity may be regulated in vivo. We show that
      estradiol benzoate activates CaMKII in a dose and time-dependent manner in mouse
      hippocampus after 30 min stimulation. The effect of estrogen is via a very rapid
      nongenomic mechanism that is blocked in vitro in hippocampal primary neurons by
      the pure estrogen receptor antagonist, ICI 182,780. These results suggest that
      estrogen action in the hippocampus is linked to CaMKII activation.

PMID- 12231260
TI  - Epileptiform burst discharges in hippocampal CA3 neurons of young but not mature
      Noda epileptic rats (NER).
AB  - Noda epileptic rat (NER), originally found in a colony of Crj; Wistar rats, shows
      spontaneous tonic-clonic convulsion characterized by the appearance of high
      voltage polyspikes in cortical and hippocampal EEG once every 2-3 days after 2-4
      months of age. Electrophysiological studies using hippocampal slice preparations
      of NER were performed to determine whether hippocampal neurons have abnormal
      excitability. When a single stimulus (1-25 V) was delivered to the mossy fibers
      of NER at 4-6 weeks old before they showed any seizures, a long-lasting
      depolarization shift (DS) accompanied by repetitive firings and after
      hyperpolarization following the abnormal firing was observed in seven of 14
      hippocampal CA3 neurons. A lower stimulation intensity evoked DS and abnormal
      firing in three of nine CA3 neurons of NER at 10-15 weeks old which had already
      showed seizures at 10-15 weeks of age. However, the abnormal firing was not
      observed in any 10 neurons of the animals at more than 20 weeks old nor in Wistar
      rats. The input impedances of CA3 neurons in NER with abnormal firing were lower
      than those without abnormal firing and those in Wistar rats. The abnormal
      excitability obtained in NER at an age when it did not display any seizures
      suggests that the hippocampus may play a role in epileptogenicity in NER.

PMID- 12231259
TI  - Testosterone regulates BCL-2 immunoreactivity in a sexually dimorphic motor pool
      of adult rats.
AB  - Bcl-2 and Bax immunoreactivity were examined in the spinal nucleus of the
      bulbocavernosus (SNB), an androgen-sensitive motor pool of adult rats. Castration
      reduced Bcl-2 immunoreactivity and testosterone treatment of castrates prevented
      this decline. Hormone manipulations did not affect Bcl-2 or Bax staining in the
      retrodorsolateral nucleus (RDLN), a relatively androgen-insensitive nucleus at
      the same spinal level. Changes in Bcl-2 expression may underlie the hormonal
      control of cell death and/or neural plasticity in SNB motoneurons.

PMID- 12231261
TI  - Organization of the hypoglossal motoneurons that innervate the horizontal and
      oblique components of the genioglossus muscle in the rat.
AB  - Anatomical studies have shown the genioglossus muscle of the tongue of mammals to
      have at least two subdivisions. One is horizontal and the other fans out
      obliquely. In the dog, the hypoglossal nerve appears to have separate branches
      for each muscle subdivision. In the rat, genioglossus muscle motoneurons have
      been reported in the lateral and centrolateral subnuclei of the ventral
      hypoglossal nucleus. Here, retrograde labeling documented that these two
      hypoglossal sub-nuclei separately supply the two components of the genioglossus
      muscle. In so doing we add new data concerning the myotopic organization of the
      hypoglossal nucleus and further clarify the functional organization of the
      hypoglossal-tongue complex into protrusor and retrusor subdivisions.

PMID- 12231262
TI  - Quality of life and standard of living in a randomly selected group of
      psychiatrically disabled people in Sweden 2 years after a psychiatry reform.
AB  - In Sweden, a psychiatry reform, aimed at improving the living conditions of the
      psychiatrically disabled, came into force in 1995. The aim of the present study
      was to evaluate the impact of the reform by investigating quality of life and
      standard of living 2 years later in a randomly selected group of people with
      longstanding psychiatric disability. Self-ratings and interviews were conducted
      in a study group and a control group. The study group consisted of 19 women and
      18 men (mean age 46.1 years) diagnosed with neurosis, schizophrenia or affective
      disorder. The control group consisted of 19 women and 17 men (mean age 48.7
      years). Self-rated quality of life was significantly poorer in the study group (P
      < 0.0001, unpaired t-test), and so was housing (P < 0.001, test of similar
      proportions in independent samples). We found no significant positive correlation
      between subjective quality of life and standard of living in either group but a
      significant negative correlation in the control group (P < 0.05; r = 0.40,
      Pearson correlation coefficient). The results suggest that, in 1997, people with
      longstanding psychiatric disability still had poorer quality of life than the
      general population. This may be due to factors other than outward standard of
      living.

PMID- 12231263
TI  - Stimulus-induced craving and startle potentiation in abstinent alcoholics and
      controls.
AB  - Abstinent alcoholics often deny craving for alcohol but still show a high level
      of relapse. The eyeblink response to startling noise was used as an indicator of
      the emotional response to alcohol-related, positive, negative and neutral visual
      stimuli in abstinent alcoholics, social drinkers and rarely drinking controls.
      The cognitive evaluation of the stimuli was assessed by ratings of subjective
      craving, valence and arousal. The startle response of the alcoholics to alcohol
      related stimuli was significantly inhibited despite an aversive overt stimulus
      evaluation. These findings indicate that alcohol-related stimuli may have
      appetitive incentive salience for alcoholics in spite of verbal reports of
      craving and valence to the opposite.

PMID- 12231264
TI  - Multisensory integration for spatial orientation in trait anxiety subjects:
      absence of visual dependence.
AB  - Studies suggest a greater reliance on visual information for maintaining balance
      in anxious subjects. Nevertheless, links between this supposed preferred visual
      processing and spatial orientation have not yet been evaluated. Two groups of
      subjects differing in their level of trait anxiety were formed. Equipped with a
      head-mounted visual display, they learned a virtual corridor using passive
      translation but active rotation, both with normal and with two different
      conflicting sensory conditions. After two visual navigation trials in the
      corridor, they were blindfolded and asked to reproduce the same trajectory from
      memory. In addition, subjects drew a map of the remembered corridor. Anxious
      subjects were comparable to non-anxious subjects when asked to reproduce the
      trajectory from memory, but exhibited a deficit when drawing a map of the
      corridor they were in. The results do not support the hypothesis that anxious
      subjects use preferentially one type of sensory cue over another for spatial
      orientation, but instead manifest difficulties in constructing more global
      representations of space.

PMID- 12231265
TI  - Are bipolar I depressive patients less responsive to treatment with
      antidepressants than unipolar depressive patients? Results from a case control
      study.
AB  - The increasing evidence that bipolar and unipolar affective disorders have
      different biological etiologies and courses of illness has been associated with
      an intensifying interest in specific treatment regimens for both disorders during
      the last decade. In this context, the question arose whether antidepressants
      exert similar efficacy in the acute treatment of bipolar compared to unipolar
      depression. Although the clinical impression does not indicate substantial
      differences in the efficacy of antidepressants between these groups of patients,
      empirical databases concerning this topic are rare. The present study compared
      the efficacy of antidepressants in 50 unipolar and 50 bipolar depressed
      inpatients (ICD-9 criteria) under naturalistic treatment conditions. Both groups
      of patients were matched for age, gender and duration of illness. Clinical
      assessments of status at the time of admission and at discharge were used to rate
      response to antidepressant treatment. Analyses of the data revealed that both
      groups of patients needed the same time for treatment response and did not show
      any significant differences in outcome measures at discharge. These findings do
      not concur with the hypothesis formulated by some experts in the field of
      affective disorders that antidepressants are less effective in the acute
      treatment of bipolar depressed patients compared to unipolar depressed patients.

PMID- 12231266
TI  - Clinical relevance of electroconvulsive therapy (ECT) in adolescents with severe
      mood disorder: evidence from a follow-up study.
AB  - Given the limited knowledge on the long-term outcome of adolescents who receive
      electroconvulsive therapy (ECT), the study aimed to follow-up adolescents treated
      with ECT for severe mood disorder. Eleven subjects treated during adolescence
      with bilateral ECT for psychotic depression (n = 6) or mania (n = 5), and ten
      psychiatric controls matched for sex, age, school level, and clinical diagnosis,
      completed at least 1 year after treatment a clinical and social evaluation. Mean
      duration between time of index episode and time of follow-up evaluation was 5.2
      years (range 2-9 years). At follow-up: (1) all patients except two in the control
      group received a diagnosis of bipolar disorder. (2) Fifteen patients had had more
      than one episode of mood disorder. (3) The two groups did not differ in social
      functioning nor school achievement. (4) Impact on school achievement was related
      to the severity of the mood disorder rather than ECT treatment. The results
      suggest that adolescents given ECT for bipolar disorder, depressed or manic, do
      not differ in subsequent school and social functioning from carefully matched
      controls.

PMID- 12231267
TI  - Costs and outcomes of risperidone treatment in schizophrenia in the Czech
      Republic.
AB  - The increasing cost of pharmaceuticals in the Czech Republic has led to
      restrictions on the prescription of more expensive atypical antipsychotics. The
      aim of the study was to compare the costs and outcomes of using risperidone
      versus classical neuroleptics in treatment of schizophrenia in order to see if
      there was any cost advantage in restricting use of more recent antipsychotics.
      Sixty-seven patients (39 women) with a mean age of 34.6 years (S.D. = 9.74)
      suffering from schizophrenia or schizoaffective disorder were treated with
      risperidone while 67 patients (39 women) with the same diagnoses with a mean age
      of 35.7 years (S.D. = 9.91) received standard neuroleptics. Yearly direct medical
      costs and outcomes (indicated by the average Global Assessment of Functioning
      score) were assessed retrospectively in an open, intent-to-treat study by
      abstracting psychiatric outpatient charts. The outcomes were not significantly
      different between the treatment groups while the risperidone treatment was
      significantly more expensive than the therapy with standard neuroleptics. This
      result which appears to be inconsistent with the literature was caused by the
      cheap labor force in the Czech Republic. The difference between the followed
      treatments in the direct costs will probably become insignificant in the future
      when the country's economy will be more developed.

PMID- 12231268
TI  - Clinical profiles relating gender and depressive symptoms among adolescents
      ascertained by the Beck Depression Inventory II.
AB  - PURPOSE: Depressive disorders (DD) in adolescence are often misdiagnosed and
      under-recognised. A major clinical problem regards the high rate of co-morbidity
      with other disorders, namely substance abuse. The aim of this study was to assess
      the discriminative power of the Beck Depression Inventory II (BDI-II) to
      characterise specific social-demographic variables related to DD in adolescence.
      METHODS: A Portuguese version of the BDI-II and a social-demographic
      questionnaire were administered to 775 Portuguese adolescents (312 males, 463
      females; mean age: 16.9 years); 83 adolescents performed a clinical interview
      following DSM-IV criteria. RESULTS: Mean BDI-II Portuguese version (BDI-II-P)
      total score was 10.31 (standard deviation: 8.4), with females reporting more
      depressive symptoms than males (P < 0.001). Low academic achievement, sleep
      disturbances, and alcohol consumption were consistently associated with
      depressive symptoms for both genders. Higher tobacco consumption was
      significantly associated with depressive symptoms in females. Familial factors
      did not appear to be associated with depressive symptoms in males. However, a
      higher frequency of siblings, having separated parents as well as a more extreme
      perception of the mother's educational style were consistently associated with
      depressive symptoms in females. CONCLUSION: The BDI-II-P showed discriminative
      power to characterise social-demographic variables related to DD especially in
      adolescent females.

PMID- 12231269
TI  - 5-HT(2A) gene promoter polymorphism as a modifying rather than a vulnerability
      factor in anorexia nervosa.
AB  - The A allele of the 5-HT(2A) gene (-1438A/G polymorphism) has been associated
      with anorexia nervosa in four studies, but not in three others. One possibility
      to explain such a discrepancy is that the A allele acts as a modifying rather
      than a vulnerability allele. To test this hypothesis, we increased our initial
      sample of 102 trios left open bracket Mol. Psychiatry 7 (2002) 90 right open
      bracket with 43 new patients with anorexia nervosa and 98 healthy controls. In
      addition to confirming the absence of association on the global sample of 145
      patients, we found that patients with the A allele had a significantly later age
      at onset of the disease (P = 0.032). Furthermore, the A allele was also
      transmitted with an older age at onset (P = 0.023) using a quantitative-trait TDT
      approach. The A allele may thus act as a modifying factor (delaying onset),
      potentially explaining variations of allele frequency across samples, in which
      differences in average age at onset are not only possible, but also expected.
      Taking into account vulnerability genes, but also genes modifying the expression
      of the disorder, will help to disentangle the complexity of the etiological
      factors involved in anorexia nervosa.

PMID- 12231270
TI  - Cyproheptadine in treatment of autism.

PMID- 12231271
TI  - Efficacy of lithium treatment in Kleine-Levin syndrome.
AB  - The Kleine-Levin syndrome (KLS) is characterized by periodic, sudden-onset
      episodes of hypersomnia, compulsive hyperphagia, and behavioral-emotional
      symptoms, lasting from a few days to a few weeks, with complete remission in the
      intercritical periods. We report on efficacy of lithium treatment in a highly
      recurring form of the disorder in a 17-year-old male adolescent. The decreasing
      severity of the disorder paralleled the progressive increase of lithium dosage,
      up to 0.9 mEq l(-1). Implications regarding the pharmacological treatment of this
      neglected disorder are discussed.

PMID- 12231272
TI  - Coexistence of Capgras and Fregoli syndromes in a single patient. Clinical,
      neuroimaging and neuropsychological findings.

PMID- 12231273
TI  - Partial hospitalization and outcome of anorexia nervosa.

PMID- 12231274
TI  - Combined clozapine and valproic acid treatment-induced agranulocytosis.

PMID- 12231275
TI  - Force enhancement above the initial isometric force on the descending limb of the
      force-length relationship.
AB  - Edman et al. (J. General Physiol. 80 (1982) 769) observed in single fibres of
      frog that the steady-state forces following active fibre stretch were greater
      than the purely isometric force obtained at the length from which the stretch was
      initiated. Operating on the descending limb of the force-length relationship,
      such a result can only be explained within the framework of the sarcomere length
      non-uniformity theory, if some fibre segments shortened during the fibre stretch.
      However, such a result was not found, leaving Edman's observation unexplained.
      Force enhancement above the initial isometric force has not been investigated
      systematically in whole muscle, and therefore it is not known whether this
      property is also part of whole muscle mechanics. The purpose of this study was to
      test if the steady-state forces following active stretch of cat semitendinosus
      were greater than the corresponding purely isometric forces at the muscle length
      from which the stretch was started. Cat semitendinosus was stretched by various
      amounts on the descending limb of the force-length relationship, and the steady
      state forces following these stretches were compared to the corresponding
      isometric forces at the initial and final muscle lengths. In 109 of 131 tests,
      the steady-state forces following stretching were greater than the isometric
      forces at the initial muscle lengths. Force enhancement increased with increasing
      amounts of stretching, and force enhancement above the initial isometric force
      was more likely to occur following stretches of great compared to small
      amplitude. Passive forces following active muscle stretching were often
      significantly greater than the passive forces at the same muscle length following
      an isometric contraction or a passive stretching of the muscle. This observation
      was made consistently at the longest muscle lengths tested. It appears,
      therefore, that there is a passive force that accounts for part of the force
      enhancement above the isometric force at the initial muscle length, and that
      provides increased passive force when a muscle is actively, rather than
      passively, stretched at long muscle lengths. We conclude that cat semitendinosus
      demonstrates steady-state force enhancement above the corresponding purely
      isometric force at the initial muscle length on the descending limb of the force
      length relationship for many contractile conditions, and that a unique, and so
      far undetected, passive, parallel element contributes to this force enhancement,
      particularly at long muscle lengths where muscle is assumed to be most vulnerable
      to injuries associated with sarcomere length instability.

PMID- 12231276
TI  - Modified pressure distribution patterns in walking following reduction of plantar
      sensation.
AB  - The aim of the present study was to investigate the influence of reduced plantar
      sensation on pressure distribution patterns during gait of 40 healthy subjects
      (25.3+/-3.3 yr, 70.8+/-10.6 kg and 176.5+/-7.8 cm) with no history of sensory
      disorders. Plantar sensation in the subjects was reduced by using an ice
      immersion approach, and reduced sensitivity was tested with Semmes-Weinstein
      monofilaments. All subjects performed six trials of barefoot walking over a
      pressure distribution platform under normal as well as iced conditions. Plantar
      cutaneous sensation was significantly reduced after the cooling procedure
      (p<0.0001). Pressure distribution analysis showed substantially modified plantar
      pressure distribution patterns during the roll-over process (ROP) under iced
      conditions. Analysis of peak pressures revealed significant reductions under the
      toes and under the heel (p<0.001). The contact time and the relative impulse for
      the whole foot did not change significantly between the two conditions. For the
      different areas, a significant load shift from the heel and toes towards the
      central and lateral forefoot and the lateral midfoot was observed. The results
      indicate the strong influence of reduced afferent information of the sole of the
      foot on the ROP in walking.

PMID- 12231277
TI  - Models of skeletal muscle to explain the increase in passive stiffness in desmin
      knockout muscle.
AB  - Absence of desmin in skeletal muscle was found to induce an increase in passive
      stiffness. The present study aimed at developing rheological models of passive
      muscle to explain this stiffening. Models were elaborated by using experimental
      data depicting muscle viscoelastic behaviour. The experimental protocol included
      stepwise extension tests applied on control and desmin knockout soleus muscles
      from mice. Linear and non-linear models were composed of elastic and viscous
      elements. They were constructed with the aim at taking the presence or absence of
      desmin into account by simulating desmin as an elastic element. Furthermore,
      associated adaptation of connective tissues in absence of desmin was modelled as
      an additional elastic element. Differences in passive behaviour induced by
      absence of desmin were predicted by using a linear model and a non-linear one.
      The non-linear model was selected because: (1) it is able to predict experimental
      viscoelastic kinetics accounting for the increase in passive stiffness in muscles
      lacking desmin, (2) its design is consistent with morphological data, and (3)
      stiffness characteristics of its elements are in accordance with the literature.
      Finally, this modelling approach demonstrates that both absence of desmin and
      adaptation of connective tissue are required to explain the increase in passive
      stiffness in desmin knockout muscles.

PMID- 12231278
TI  - The influence of the acetabular labrum seal, intact articular superficial zone
      and synovial fluid thixotropy on squeeze-film lubrication of a spherical synovial
      joint.
AB  - A model of synovial fluid (SF) filtration by articular cartilage (AC) in a step
      loaded spherical synovial joint at rest is presented. The effects of joint
      pathology (such as a depleted acetabular labrum, a depleted cartilage superficial
      zone consistent with early osteoarthritis and an inflammatory SF) on the squeezed
      synovial film are also investigated. Biphasic mixture models for AC (ideal fluid
      and elastic porous transversely isotropic two-layer matrix) and for SF (ideal and
      thixotropic fluids) are applied and the following results are obtained. If the
      acetabular labrum is able to seal the pressurised SF between the articular
      surfaces (as in the normal hip joint), the fluid in the synovial film and in the
      cartilage within the labral ring is homogeneously pressurised. The articular
      surfaces remain separated by a fluid film for minutes. If the labrum is destroyed
      or absent and the SF can escape across the contact edge, the fluid pressure is
      non-homogeneous and with a small jump at the articular surface at the very moment
      of load application. The ensuing synovial film filtration by porous cartilage is
      lower for the normal cartilage (with the intact superficial zone) than if this
      zone is already depleted or rubbed off as in the early stage of primary
      osteoarthritis. Compared with the inflammatory (Newtonian) SF, the normal
      (thixotropic) fluid applies favourably in the squeezed film near the contact
      centre only, yielding a thicker SF film there, but not affecting the minimum
      thickness in the fluid film profile at a fixed time. For all that, in the
      unsealed case for both the normal and pathological joint, the macromolecular
      concentration of the hyaluronic acid-protein complex in the synovial film quickly
      increases due to the filtration in the greater part of the contact. A stable
      synovial gel film, thick on the order of 10(-7)m, protecting the articular
      surfaces from the intimate contact, is formed within a couple of seconds.
      Boundary lubrication by the synovial gel is established if sliding motion follows
      until a fresh SF is entrained into the contact. This theoretical prediction is
      open for experimental verifications.

PMID- 12231279
TI  - Is there a haemodynamic advantage associated with cuffed arterial anastomoses?
AB  - The development of intimal hyperplasia at arterial bypass graft anastomoses is a
      major factor responsible for graft failure. A revised surgical technique,
      involving the incorporation of a small section of vein (vein cuff) into the
      distal anastomosis of PTFE grafts, results in an altered distribution of intimal
      hyperplasia and improved graft patency rates, especially for below-knee grafts.
      Numerical simulations have been conducted under physiological conditions to
      identify the flow behaviour in a typical cuffed bypass model and to determine
      whether the improved performance of the cuffed system can be accounted for by
      haemodynamic factors. The flow patterns at the cuffed anastomosis are
      significantly different to those at the conventional end-to-side anastomosis. In
      the former case, the flow is characterised by an expansive, low momentum
      recirculation within the cuff. Separation occurs at the graft heel, and at the
      cuff toe as the blood enters the recipient artery. Wall shear stresses in the
      vicinity of the cuff heel are low, but high shear stresses and large spatial
      gradients in the shearing force act on the artery floor during systole. In
      contrast, a less disturbed flow prevails and the floor shear stress distribution
      is less adverse in the conventional model. In conclusion, aspects of the
      anastomotic haemodynamics are worsened when the cuff is employed. The benefits
      associated with the cuffed grafts may be related primarily to the presence of
      venous material at the anastomosis. Therefore, caution is advised with regard to
      the use of PTFE grafts, pre-shaped to resemble a cuffed geometry.

PMID- 12231280
TI  - Blood flow patterns in an anatomically realistic coronary vessel: influence of
      three different reconstruction methods.
AB  - Many clinical studies suggest that local blood flow patterns are involved in the
      location and development of atherosclerosis. In coronary diseases, this
      assumption should be corroborated by quantitative information on local
      hemodynamic parameters such as pressure, velocity or wall shear stress. Nowadays,
      computational fluid dynamics (CFD) algorithms coupled to realistic 3-D
      reconstructions of such vessels make these data accessible. Nevertheless, they
      should be carefully analysed to avoid misinterpretations when the physiological
      parameters are not all considered. As an example, we propose here to compare the
      flow patterns calculated in a coronary vessel reconstructed by three different
      methods. In the three cases, the vessel trajectory respected the physiology. In
      the simplest reconstruction, the coronary was modelled by a tube of constant
      diameter while in the most complex one, the cross-sections corresponded to the
      reality. We showed that local pressures, wall shear rates and velocity profiles
      were severely affected by the geometrical modifications. In the constant cross
      section vessel, the flow resembled to that of Poiseuille in a straight tube. On
      the contrary, velocity and shear rate exhibited sudden local variations in the
      more realistic vessels. As an example, velocity could be multiplied by 5 as
      compared to Poiseuille's flow and area of very low wall shear rates appeared. The
      results obtained with the most complex model clearly outlined that, in addition
      to a proper description of the vessel trajectory, the section area changes should
      be carefully taken into account, confirming assumptions already highlighted
      before the rise of commercially available and efficient CFD softwares.

PMID- 12231281
TI  - A dynamic 3D biomechanical evaluation of the load on the low back during
      different patient-handling tasks.
AB  - The objective of this study was to investigate the low-back loading during common
      patient-handling tasks. Ten female health care workers without formal training in
      patient handling performed nine patient-handling tasks including turning, lifting
      and repositioning a male stroke patient. The low-back loading was quantified by
      net moment, compression, and shear forces at the L4/L5 joint, measured muscle
      activity (EMG) in erector spinae muscles and rate of perceived exertion (RPE;
      Borg scale). The experiments were videotaped with a 50Hz video system using five
      cameras, and the ground and bedside reaction forces of the health care worker
      were recorded by means of force platforms and force transducers on the bed. The
      biomechanical load was calculated using a dynamic 3D seven-segment model of the
      lower part of the body, and the forces at the L4/L5 joint were estimated by a 14
      muscles cross-sectional model of the low back (optimisation procedure).
      Compression force and torque showed high task dependency whereas the EMG data and
      the RPE values were more dependent on the subject. The peak compression during
      two tasks involving lifting the patient (4132/4433N) was significantly higher
      than all other tasks. Four tasks involving repositioning the patient in the bed
      (3179/3091/2932/3094N) did not differ, but showed higher peak compression than
      two tasks turning the patient in the bed (1618/2197N). Thus, in this study the
      patient-handling tasks could be classified into three groups-characterised by
      lifting, repositioning or turning-with different levels of peak net torque and
      compression at the L4/L5 joint.

PMID- 12231282
TI  - Inter-individual variations in wall shear stress and mechanical stress
      distributions at the carotid artery bifurcation of healthy humans.
AB  - Fluid shear stress and mechanical wall stress may play a role in the formation of
      early atherosclerotic lesions, but these quantities are difficult to measure in
      vivo. Our objective was to quantify these parameters in normal subjects in a
      clinical setting, and to define regions of low wall shear stress and high
      mechanical stress. The right carotid bifurcations of five healthy male volunteers
      were investigated using a novel non-invasive technique which integrates magnetic
      resonance angiography, ultrasonography, tonometry and state-of-the-art
      computational fluid dynamics and solid mechanics models. Significant inter
      subject variations in patterns as well as magnitude of wall shear stress and
      mechanical stress were found. In spite of individual variabilities, this study
      revealed that some regions of the artery wall are exposed simultaneously to low
      wall shear stress and high mechanical stress and that these regions correspond to
      areas where atherosclerotic plaque develops. The coexistence of regions of low
      wall shear stress and high tensile stress may be an important determinant of the
      formation of atheroma in human arteries.

PMID- 12231283
TI  - Strain-rate sensitivity of the rabbit MCL diminishes at traumatic loading rates.
AB  - This study was performed to determine whether the viscoelastic behavior of
      ligaments persists at high rates of loading, such as those associated with sports
      related trauma or motor vehicle accidents. Medial collateral ligaments (MCLs)
      from 22 skeletally mature New Zealand White rabbits were tensile tested quasi
      statically and via two impact conditions at displacement rates of 0.17 mm/s
      (n=22), 640+/-160 mm/s (n=10) and 2500+/-270 mm/s (n=12) (corresponding to strain
      rates of approximately 1.0%/s, 3660%/s and 14,000%/s, respectively). Despite
      dramatic increases in displacement rate, only a modest strain-rate effect was
      observed when the specimens tested quasi-statically were compared to those tested
      via impact (24% and 37% increases in stiffness and failure load, respectively).
      There were no differences in the structural (e.g. 145+/-30 and 136+/-29 N/mm
      stiffness values, respectively) or failure properties (e.g. 434+/-91 and 443+/
      154 N failure load values, respectively) of the two impact-tested groups. Our
      findings suggest that the rabbit MCL is not viscoelastic at loading rates
      approximating those associated with high-energy trauma.

PMID- 12231284
TI  - Mechanical efficiency of cycling with a new developed pedal-crank.
AB  - The mechanical efficiency of cycling with a new pedal-crank prototype (PP) was
      investigated during an incremental test on a stationary cycloergometer. The
      efficiency values were compared with those obtained, in the same experimental
      conditions and with the same subjects, by using a standard pedal-crank system
      (SP). The main feature of this prototype is that its pedal-crank length changes
      as a function of the crank angle being maximal during the pushing phase and
      minimal during the recovery one. This variability was expected to lead to a
      decrease in the energy requirement of cycling since, for any given thrust, the
      torque exerted by the pushing leg is increased while the counter-torque exerted
      by the contra-lateral one is decreased. Whereas no significant differences were
      found between the two pedal-cranks at low exercise intensities (w*=50-200 W), at
      250-300 W the oxygen uptake (V*O2, W) was found to be significantly lower and the
      efficiency (eta=w*/V*O2) about 2% larger (p<0.05, Wilcoxon test) in the case of
      PP. Even if the measured difference in efficiency was rather small, it can be
      calculated that an athlete riding a bicycle equipped with the patented pedal
      crank could improve his 1h record by about 1 km.

PMID- 12231285
TI  - Two-dimensional viscous flow between slowly expanding or contracting walls with
      weak permeability.
AB  - Since the transport of biological fluids through contracting or expanding vessels
      is characterized by low seepage Reynolds numbers, the current study focuses on
      the viscous flow driven by small wall contractions and expansions of two weakly
      permeable walls. The scope is limited to two-dimensional symmetrical solutions
      inside a simulated channel with moving porous walls. In seeking an exact
      solution, similarity transformations are used in both space and time. The problem
      is first reduced to a nonlinear differential equation that is later solved both
      numerically and analytically. The analytical procedure is based on double
      perturbations in the permeation Reynolds number R and the wall expansion ratio
      alpha. Results are correlated and compared via variations in R and alpha. Under
      the auspices of small [R] and [alpha], the analytical result constitutes a
      practical equivalent to the numerical solution. We find that, when suction is
      coupled with wall contraction, rapid flow turning is precipitated near the wall
      where the boundary layer is formed. Conversely, when injection is paired with
      wall expansion, the flow adjacent to the wall is delayed. In this case, the
      viscous boundary layer thickens as injection or expansion rates are reduced.
      Furthermore, the pressure drop along the plane of symmetry increases when the
      rate of contraction is increased and when either the rate of expansion or
      permeation is reduced. As nonlinearity is retained, our solutions are valid from
      a large cross-section down to the state of a completely collapsed system.

PMID- 12231286
TI  - An iterative method for viscoelastic modeling of prosthetic feet.
AB  - Prosthetic foot designs are growing in complexity, but a few material and
      structural properties, including stiffness and viscoelasticity, remain critical
      to foot function. Consistent identification of these critical properties would
      aid prosthesis prescription. This investigation evaluates a new technique to
      model prosthetic feet as a combination of springs and dampers, and therefore
      characterize a foot's stiffness and viscoelasticity by means of spring and damper
      coefficients. A quasi-Newton iterative algorithm was developed to determine model
      coefficients for 9 prosthetic feet based on compressive creep, stress-relaxation,
      and constant strain rate tests. A broad range of current energy-storing feet
      including designs from Otto Bock, Seattle, Kingsley, and Ohio Willow Wood were
      very accurately modeled with the iterative technique. Feet without a solid ankle
      from Flex and College Park were the least accurately modeled. The Flex foot,
      tested without a cover, had a considerably lower damping coefficient. Damper
      coefficients were similar for most all other feet, suggesting similar material
      properties of the foam cover. Stiffness varied and generally agreed with
      published data. The ability of the model to produce two separate parallel spring
      stiffness constants might provide insight into foot structure. The model
      represents a means to objectively quantify material properties for a range of
      solid ankle dynamic elastic response prosthetic feet, but may be limited in its
      characterization of other foot varieties.

PMID- 12231287
TI  - Quasi-linear viscoelastic behavior of the human periodontal ligament.
AB  - Previous studies have not produced a comprehensive mathematical description of
      the nonlinear viscoelastic stress-strain behavior of the periodontal ligament
      (PDL). In the present study, the quasi-linear viscoelastic (QLV) model was
      applied to mechanical tests of the human PDL. Transverse sections of cadaveric
      premolars were subjected to relaxation tests and loading to failure perpendicular
      to the plane of section. Distinct and repeatable toe and linear regions of stress
      strain behavior were observed. The amount of strain associated with the toe
      region differed as a function of anatomical location along the tooth root. Stress
      relaxation behavior was comparable for different anatomical locations. Model
      predicted peak tissue stresses for cyclic loading were within 11% of experimental
      values, demonstrating that the QLV approach provided an improved, accurate
      quantification of PDL mechanical response. The success of the QLV approach
      supports its usefulness in future efforts of experimental characterization of PDL
      mechanical behavior.

PMID- 12231288
TI  - Mechanical properties of the human gastrointestinal tract.
AB  - The tensile properties of the human esophagus, stomach, small and large bowel
      were examined on an Instron 1221 tensiometer. The values of maximal stress and
      destructive strain were the following: for esophagus-1.2 MPa and 140%,
      respectively, for stomach axial specimens-0.7 MPa and 190%, for stomach
      transversal specimens-0.5 MPa and 190%, for small bowel transversal specimens-0.9
      MPa and 140% and for large bowel transversal specimens-0.9 MPa and 180%. Tests
      conducted on small and large bowel axial specimens permitted examination of the
      intestinal wall as a multi-layered structure. The mechanical properties of tested
      bowels in axial and transversal directions were qualitatively different. The
      submucosa and muscular layers condition the mechanical strength of bowel wall,
      while the serosa and mucosa showed no significant strength. Reproducible results
      were generated for cadaveric and surgically removed stomach and small intestine,
      which showed their mechanical properties similar under certain storage
      conditions. The data received could be used for monitoring of the mechanical
      properties of bowel wall layers under different conditions and for checking of
      bowel distension sequences.

PMID- 12231289
TI  - Hydraulic functional characterisation of aortic mechanical heart valve prostheses
      through lumped-parameter modelling.
AB  - Lumped-parameter modelling techniques are proposed as a method for studying the
      hydraulic characteristics of mechanical prosthetic heart valves (PHVs). The
      global hydraulic behaviour of PHVs in the open position was modelled by taking
      into account the (nonlinear) resistive and (linear) inertial factors governing
      the time-dependent relationship between transvalvular pressure drop and fluid
      flow rate, and neglecting the leaflets' opening and closure transient phenomena.
      Statistically defined indices associated to the parameters' values attest how
      properly the model describes PHV hydraulic behaviour. Local fluid dynamics is not
      modelled with this approach. The proposed method was implemented in a software
      program and applied to the characterisation of the aortic StJude Medical, StJude
      Medical Hemodynamic Plus and CarboMedics PHVs, basing on steady- and pulsatile
      flow hydraulic-bench experimental data. The results showed that reliable
      parameters expressing hydraulic resistance can be derived from steady-flow data
      (R(2)>0.995). Inertance parameters derived from pulsatile-flow experiments are
      liable to a degree of uncertainty (confidence intervals up to 17%), however,
      comparing the reconstructed vs. measured pressure drop during systolic time
      demonstrates that this deficiency is mostly due to the missing description of
      initial, transient oscillations presumably related to the leaflets' opening (not
      modelled).

PMID- 12231290
TI  - In response to "Sensitivity of predicted muscle forces to parameters of the
      optimization-based human leg model revealed by analytical and numerical analysis"
      by R.T. Raikova and B.I. Prilutsky and "A physiologically based criterion of
      muscle force prediction in locomotion" by R.D. Crowninsheild and R.A. Brand.

PMID- 12231291
TI  - OVDs. viscosurgical, viscoelastic, and viscoadaptive. What does this mean?

PMID- 12231294
TI  - No-anesthesia phacoemulsification.

PMID- 12231292
TI  - Efficient and economical follow-up after phacoemulsification.

PMID- 12231296
TI  - Unilateral endophthalmitis after simultaneous bilateral cataract surgery.

PMID- 12231297
TI  - Corneal endothelial cell destruction by intraocular use of benzalkonium chloride.

PMID- 12231298
TI  - Consultation section. Refractive surgical problem.

PMID- 12231302
TI  - Using BSS with viscoadaptives in the ultimate soft-shell technique.
AB  - The ultimate soft-shell technique compartmentalizes the anterior chamber using
      the ultimate low-viscosity fluid--water (as balanced salt solution [BSS] or
      trypan blue [Vision Blue])--in combination with 1 of 2 commercially available
      viscoadaptive ophthalmic viscosurgical devices: Healon5 (sodium hyaluronate 2.3%)
      or I-Visc Phaco (sodium hyaluronate 2.5%). The use of this technique facilitates
      cataract surgery with viscoadaptive OVDs and viscoadaptive removal at the end of
      the procedure.

PMID- 12231303
TI  - Viscoelastic levitation of posteriorly dislocated intraocular lenses from the
      anterior vitreous.
AB  - In 5 consecutive cases presenting between 2000 and 2001, Viscoat injected via a
      pars plana sclerotomy was used to support and levitate 5 posteriorly dislocated
      IOLs into the pupillary plane. All 5 IOLs had dislocated into the anterior
      vitreous. This technique permitted successful exchange or suture refixation of
      the dislocated IOLs through limbal incisions in all cases. Diabetic macular edema
      accounted for a visual acuity of 20/60 in 1 patient. In the other patients, there
      were no significant corneal or retinal complications from the surgery and each
      regained a best corrected visual acuity of 20/40 or better.

PMID- 12231304
TI  - Healon5 tamponade of corneal perforation during transplantation surgery.
AB  - In "a chaud" keratoplasty in cases of corneal perforation, the main difficulty is
      the trephination of the recipient cornea in a soft eye. A temporary tamponade of
      the perforation can be provided by filling the anterior chamber with sodium
      hyaluronate 2.3% (Healon5). The cornea can then be grasped with vacuum and
      trephinated.

PMID- 12231305
TI  - Hyperopic laser in situ keratomileusis for refractive accommodative esotropia.
AB  - PURPOSE: To assess the efficacy of hyperopic laser in situ keratomileusis (LASIK)
      in creating orthophoria without optical correction in adult patients with
      refractive accommodative esotropia (RAE). SETTING: Instituto Oftalmologico de
      Sabadell, Sabadell, Barcelona, Spain. METHODS: This prospective single-center
      clinical trial studied 9 eyes (18 patients) with RAE having hyperopic LASIK. The
      mean follow-up was 20 months (range 12 to 24 months). The mean preoperative
      refraction was +5.01 diopters (D) and the mean deviation angle without optical
      correction, 36 prism diopters. The intervention was hyperopic LASIK using the
      Automated Corneal Shaper microkeratome (Bausch & Lomb) and the Apollo broad-beam
      excimer laser using a 5.5 mm optical zone and an 8.0 mm transition zone;
      astigmatism was treated by steepening the flattest meridian. RESULTS: All
      patients achieved orthophoria or the preoperative microtropia without optical
      correction immediately after surgery. This was maintained throughout the follow
      up. Fifty-six percent of all cases were within +/-0.5 D of emmetropia, and 89%
      were within +/-1.0 D. The uncorrected visual acuity improved significantly (P
      <.005), especially at near, and the mean best corrected visual acuity (BCVA) was
      maintained, although 4 eyes (22%) lost 1 line of BCVA. There were no significant
      complications. CONCLUSIONS: In adult patients with RAE, treatment of the
      refractive error using hyperopic LASIK was safe and effective and corrected the
      esodeviation. Further studies in younger patients will help determine the age at
      which this intervention may be indicated.

PMID- 12231306
TI  - Factors that influence outcomes of hyperopic laser in situ keratomileusis.
AB  - PURPOSE: To analyze the influence of preoperative corneal curvature,
      postoperative keratometric power, and the amount of correction on the outcomes of
      hyperopic laser in situ keratomileusis (LASIK). SETTING: Clinica Baviera,
      Instituto Oftalmologico Europeo, Madrid, Spain. METHODS: In this retrospective
      study, the records of 376 eyes that had LASIK for hyperopia using the Moria LSK
      One microkeratome and the Technolas-Keracor 217C excimer laser were reviewed. The
      results were analyzed by preoperative hyperopia (5 subgroups) and by preoperative
      (more than and less than 43.0 diopters [D]) and postoperative (more than and less
      than 48.0 D) mean keratometry. RESULTS: A statistically significant keratometry
      regression was found in the +3.00 to +3.90 D range (P <.01), a significant
      decrease in predictability in the +4.00 to +4.90 D range (P <.05), and a
      significant worsening in safety in the highest range (+6.00 to +7.90 D; P <.05).
      Comparative analysis of the > or = +4.00 D and <+4.00 D groups showed
      statistically significant differences in most measurement parameters. The
      preoperative keratometry did not influence postoperative results with the
      exception of poorer predictability in the group of preoperative flat corneas in
      which a high degree of hyperopia was corrected; ie, spherical equivalents within
      +/-0.50 D were found in 40.4% and 61.0% of cases with flat and steep corneas,
      respectively (P <.05). The efficacy and safety in eyes that achieved a
      postoperative keratometry >48.00 D did not differ significantly from the efficacy
      and safety in eyes that had a lower final keratometric power. CONCLUSIONS: The
      factor that negatively influenced the outcome of hyperopic LASIK was the degree
      of hyperopia corrected. Preoperative keratometry did not significantly influence
      the postoperative results, and postoperative keratometry >48 D did not result in
      significant worsening of visual results when the attempted correction was less
      than +4.00 D.

PMID- 12231307
TI  - Corneal asphericity after hyperopic laser in situ keratomileusis.
AB  - PURPOSE: To analyze corneal asphericity after hyperopic laser in situ
      keratomileusis (LASIK) and its relationship to the clinical outcomes. SETTING:
      Corneal and Refractive Surgery Service, Massachusetts Eye and Ear Infirmary,
      Boston, Massachusetts, USA. METHODS: In a retrospective case series, 23 patients
      (33 eyes) with hyperopia or hyperopic astigmatism who had LASIK were evaluated. A
      computer program (Holladay Diagnostic Summary, EyeSys Laboratories) was used to
      analyze corneal asphericity (Q) before and after LASIK. Corneal asphericity was
      evaluated to determine the association with the postoperative refractive error,
      best spectacle-corrected visual acuity (BSCVA), uncorrected visual acuity (UCVA),
      achieved refractive correction, mean corneal power (K), refractive yield
      (achieved/attempted correction), and keratometric yield (change in
      keratometry/attempted correction). RESULTS: After hyperopic LASIK, all corneas
      exhibited increased negative central Q. The postoperative corneal radius of
      curvature, BSCVA, and refractive and keratometric yields were not significantly
      correlated with the preoperative Q values. The asphericity change, Delta Q, was
      highly correlated with the achieved correction (r = 0.747, P <.0001). The
      postoperative Q value correlated well with the preoperative value (r = 0.534, P
      <.05) and the achieved correction (r = 0.601, P <.05) but not with the Delta Q.
      Neither the postoperative Q nor the Delta Q was correlated with the spherical
      equivalent, K, BSCVA, or UCVA. CONCLUSIONS: Asphericity may be a useful
      quantitative descriptor of the corneal optical contour after hyperopic LASIK.
      Negative central Q increased after hyperopic LASIK, especially when greater
      degrees of refractive correction were attempted.

PMID- 12231308
TI  - Efficacy and safety of the soft-shell technique in cases with a hard lens
      nucleus.
AB  - PURPOSE: To evaluate the efficacy and safety of the soft-shell technique in
      reducing corneal endothelial cell damage during cataract surgery in patients with
      a hard lens nucleus. SETTING: Miyata Eye Hospital, Miyakonojo, Miyazaki, Japan.
      METHODS: Sixty eyes of 57 cataract patients with a hard lens nucleus (Emery
      Little classification grade 3 or higher) had phacoemulsification using the soft
      shell technique with Healon((R)) (sodium hyaluronate 1%) and Viscoat (sodium
      hyaluronate 3.0%-chondroitin sulfate 4.0%) (soft-shell group) or with Healon
      alone (control group). The visual acuity, intraocular pressure (IOP), flare
      intensity in the anterior chamber, central corneal thickness, and corneal
      endothelial cell density were evaluated postoperatively. RESULTS: There were no
      significant IOP elevations in either group. The mean central corneal thickness in
      the control group was 539 microm +/- 26.0 (SD) preoperatively and 578 +/- 52.0
      microm 1 day after surgery; the increase was significant (P =.0154). There was no
      significant change in the central corneal thickness in the soft-shell group.
      There were no statistically significant differences between the 2 groups in
      uncorrected visual acuity, best corrected visual acuity, IOP, flare intensity in
      the anterior chamber, and central corneal thickness throughout the follow-up. The
      rate of endothelial cell loss 3 months after surgery was 6.4% +/- 9.6% in the
      soft-shell group and 16.3% +/- 9.8% in the control group (P =.0003). CONCLUSION:
      The results suggest that the soft-shell technique is safe and effective in
      protecting corneal endothelial cells during cataract surgery in patients with a
      hard lens nucleus.

PMID- 12231309
TI  - Transient corneal edema after phacoemulsification: comparison of 3 viscoelastic
      regimens.
AB  - PURPOSE: To evaluate the effect of different viscoelastic substances on the grade
      and time course of postoperative corneal edema. SETTING: Department of Clinical
      Sciences/Ophthalmology, Umea University Hospital, Umea, Sweden. METHODS: This
      study comprised 62 patients with otherwise healthy eyes who had routine
      phacoemulsification and intraocular lens (IOL) implantation. Patients were
      divided into 3 groups. Group 1 was given Healon GV (sodium hyaluronate 1.4%) at
      phacoemulsification and IOL implantation. Group 2 was given Viscoat (sodium
      hyaluronate 3.0%-chondroitin sulfate 4.0%) at phacoemulsification and Healon GV
      at IOL implantation. Group 3 was given Viscoat at phacoemulsification and Provisc
      (sodium hyaluronate 1.0%) at lens implantation. The central corneal thickness was
      measured with ultrasonic pachymetry before surgery and 5 and 24 hours, 1 week,
      and 1 month after surgery. RESULTS: The mean increase in corneal thickness was
      significantly greater in Group 1 than in the other 2 groups 5 and 24 hours and 1
      week after surgery. CONCLUSIONS: The transient postoperative increase in central
      corneal thickness was greater in patients receiving Healon GV during
      phacoemulsification than in patients receiving Viscoat. The use of Provisc or
      Healon GV for IOL implantation did not affect the postoperative corneal thickness
      when Viscoat was used for phacoemulsification. The time course of the edema may
      be explained by a difference between the 2 agents in endothelial protection from
      ultrasonic, mechanical, or irrigation trauma.

PMID- 12231310
TI  - Corneal endothelial cell protection during phacoemulsification: low- versus high
      molecular-weight sodium hyaluronate.
AB  - PURPOSE: To compare the efficacy of low- and high-molecular-weight sodium
      hyaluronate in protecting corneal endothelial cells during phacoemulsification.
      SETTING: Miyata Eye Hospital, Miyakonojo, Miyazaki, Japan. METHODS: One hundred
      forty-nine eyes of 136 cataract patients were randomly assigned to have cataract
      surgery using sodium hyaluronate 1% with a low molecular weight (0.6 to 1.2
      million d, Opegan) or sodium hyaluronate 1% with a high molecular weight (4
      million d, Healon) during phacoemulsification. Each group was divided into 2
      subgroups depending on the amount of ultrasound (% min) used during
      phacoemulsification, which was defined as the mean phacoemulsification energy (%)
      multiplied by phacoemulsification time (minutes). Corneal endothelial cell
      density was examined preoperatively and 3 months after surgery. The rate of cell
      loss was compared between the subgroups in the Opegan group and the Healon group.
      RESULTS: In the subgroups with ultrasound of 50% min or less, the mean rate of
      endothelial cell loss 3 months after surgery was 3.2% +/- 4.1% (SD) in the Opegan
      group and 5.9% +/- 5.3% in the Healon group (P =.0214). In the subgroups with
      ultrasound over 50% min, the mean rate of endothelial cell loss 3 months after
      surgery was 7.5% +/- 10.6% in the Opegan group and 14.8 +/- 9.0% in the Healon
      group (P =.0029). CONCLUSIONS: The results suggest that Opegan is more effective
      than Healon in protecting corneal endothelial cells during phacoemulsification
      regardless of the amount of ultrasound energy used.

PMID- 12231311
TI  - Healon5: comparison of 2 removal techniques.
AB  - PURPOSE: To evaluate the effect on intraocular pressure (IOP) of the rock 'n roll
      and behind-the-lens techniques of removing Healon(R)5 (sodium hyaluronate 2.3%).
      SETTING: St. Erik's Eye Hospital, Stockholm, Sweden. METHODS: In a prospective
      randomized study of 159 patients, 2 techniques to remove Healon5--rock 'n roll
      and behind-the-lens--were compared during cataract surgery. Cataract surgery
      included identical phacoemulsification performed by 1 surgeon and implantation of
      a silicone intraocular lens (IOL) in the capsular bag. The removal time of
      Healon5 was recorded. The IOP was measured preoperatively and 5 and 24 hours
      postoperatively. RESULTS: The mean IOP before surgery was 15.7 mm Hg +/- 2.8 (SD)
      in the rock 'n roll group and 15.9 +/- 2.7 mm Hg in the behind-the-lens group.
      Five hours postoperatively, the mean IOP was 25.6 +/- 10.4 mm Hg and 22.4 +/- 7.6
      mm Hg, respectively; the difference between the groups was statistically
      significant. By 24 hours postoperatively, the mean IOP was at preoperative levels
      in both groups. The mean removal time of Healon5 was 50 seconds in the rock 'n
      roll group and 39 seconds in the behind-the-lens group; the difference between
      the groups was statistically significant. CONCLUSIONS: Results indicate that the
      behind-the-lens technique for removing Healon5 is quicker and safer than the rock
      'n roll technique.

PMID- 12231312
TI  - Posterior capsule folds and removal of ophthalmic viscosurgical devices.
AB  - PURPOSE: To evaluate the relationship between posterior capsule folds and an
      ophthalmic viscosurgical device (OVD) during cataract surgery. SETTING: Parkland
      Memorial Hospital, Dallas, Texas, USA. METHODS: A prospective observational study
      of 91 consecutive uneventful cataract extractions by phacoemulsification was
      performed. The presence or absence of posterior capsule folds was noted
      immediately after intraocular lens (IOL) implantation and after OVD removal.
      RESULTS: Posterior capsule folds were present in 21 of 49 cases (43%) with an
      MA60BM lens (Alcon Laboratories) and in 1 of 42 cases (2%) with an SA30AL lens.
      In the MA60BM group with folds, the folds were noted before OVD removal in 14
      cases and after OVD removal in 16 cases. There was no significant difference in
      age, sex, axial length, horizontal corneal diameter, or IOL power between groups
      with and without posterior capsule folds. CONCLUSIONS: The presence of posterior
      capsule folds does not reliably signify the complete removal of OVDs.

PMID- 12231313
TI  - Intracorneal rings to correct corneal ectasia after laser in situ keratomileusis.
AB  - PURPOSE: To evaluate the potential of using intrastromal corneal ring technology
      (Intacs, KeraVision) to correct posterior ectasia after laser in situ
      keratomileusis (LASIK) for myopia. SETTING: Department of Cornea and Refractive
      Surgery, Instituto Oftalmologico de Alicante, and Miguel Hernandez University
      School of Medicine, Alicante, Spain. METHODS: In this prospective noncomparative
      intervention case series, Intacs segments were implanted in 3 eyes that developed
      posterior ectasia after myopic LASIK with clear central corneas. Posterior
      ectasia and corneal thickness were tested using the Orbscan II Slit Scanning
      Corneal Topography/Pachymetry System (Orbtek Inc.). Segment thickness varied
      based on corneal topography analysis and refraction. The mean follow-up was 8.3
      months (range 7 to 11 months). RESULTS: The cases showed marked improvement after
      Intacs segment implantation. Postoperatively, there was a reduction in the
      magnitude of the posterior and anterior corneal surface steepening or ectasia and
      an increase in the topographical regularity index. In addition, the significantly
      enlarged optical zones resulted in a favorable visual outcome. In 2 eyes, the
      uncorrected visual acuity (UCVA) was 20/40 postoperatively. In the third eye,
      there was a residual refractive error; the UCVA was 20/50 and the best spectacle
      corrected visual acuity, 20/40. CONCLUSIONS: Intacs intrastromal corneal rings
      used as a mechanical device may alter the biomechanical properties of the cornea
      for the correction of iatrogenic keratectasia and the associated residual myopia.

PMID- 12231314
TI  - Refractive change in response to acute hyperbaric stress in refractive surgery
      patients.
AB  - PURPOSE: To determine whether acute hyperbaric stress affects visual acuity or
      refractive power after keratorefractive surgery. SETTING: Clinical multiplace
      hyperbaric chamber and ophthalmology clinic, University of California, San Diego,
      California, USA. METHODS: This prospective convenience sample study included 3
      groups: 3 patients who had had bilateral myopic radial keratotomy (RK); 2 who had
      had bilateral myopic laser in situ keratomileusis (LASIK); and 4 control subjects
      who had no previous corneal refractive surgery or ocular pathology but had a
      myopic refractive error (-1.25 to -8.38 diopters [D]) similar to that in the
      treated patients before refractive surgery. One additional patient had had
      unilateral LASIK only and was included in the LASIK and control groups. Best
      spectacle-corrected visual acuity (BSCVA), manifest spherocylindrical refractive
      error, and intraocular pressure were measured at baseline, at 4 atmospheres
      absolute (atm abs), and on return to ambient pressure. Corneal pachymetry and
      keratometry were measured at baseline and on return to ambient pressure. RESULTS:
      The mean BSCVA changed from 0.06 logMAR (20/25 Snellen equivalent) at baseline to
      0.10 logMAR (20/25) at 4 atm abs in the RK group and from 0.00 logMAR (20/20) to 
      0.06 logMAR (20/15) in the LASIK group; it did not change in the control group.
      The mean refractive error changed from 0.25 D at baseline to 0.50 D at 4 atm abs
      in the RK group, from -0.90 to -1.02 D in the LASIK group, and from -4.58 to 
      4.53 D in the control group. CONCLUSIONS: Acute hyperbaric stress did not appear
      to alter refractive power after corneal surgery.

PMID- 12231315
TI  - Comparison of sonic and ultrasonic phacoemulsification using the Staar Sonic Wave
      system.
AB  - PURPOSE: To compare the performance of sonic phacoemulsification with that of
      ultrasonic phacoemulsification in regard to 1-day postoperative visual acuity,
      corneal edema, and procedure efficiency. SETTING: Oregon Eye Institute, Eugene,
      Oregon, USA. METHODS: This prospective nonrandomized study comprised 86 eyes with
      mild to moderate nuclear sclerotic cataract. Forty-three eyes had sonic and 43
      ultrasonic phacoemulsification using the Staar Sonic Wave phacoemulsification
      system. The mean age was 76 years in the ultrasonic group and 71 years in the
      sonic group. The mean nuclear sclerosis was 2.0+ in the sonic group and 1.9+ in
      the ultrasonic group. Patient age, lens density, postoperative corneal edema, 1
      day postoperative uncorrected visual acuity (UCVA), and the percentage of eyes
      with a visual acuity of 20/40 or better were determined. In addition, the mean
      ultrasonic and sonic times, mean percentage phaco power, and mean effective phaco
      time (EPT) were calculated in each group. RESULTS: Both groups had a 5% incidence
      of trace corneal edema. The mean UCVA was 20/41 in the ultrasonic group and 20/42
      in the sonic group. Seventy-nine percent of eyes in the ultrasonic group and 74%
      in the sonic group had a UCVA of 20/40. The mean percentage phaco power was 7.2%
      and 7.6% in the ultrasonic group and sonic group, respectively. The mean EPT was
      low in both groups, 4.0 and 2.9 seconds, respectively. CONCLUSION: Sonic
      technology yielded outcomes similar to those of ultrasonic phacoemulsification
      with respect to postoperative visual acuity and corneal edema in patients with
      average density nuclear sclerotic cataract.

PMID- 12231316
TI  - Combined toric intraocular lens implantation and relaxing incisions to reduce
      high preexisting astigmatism.
AB  - PURPOSE: To evaluate whether combining toric intraocular lens (IOL) implantation
      with astigmatic keratotomy (AK) can correct higher levels of astigmatism while
      minimizing undue effects on the optical qualities of the cornea. SETTING: St.
      Luke's Cataract and Laser Institute, Tarpon Springs, Florida, USA. METHODS:
      Thirteen eyes with corneal astigmatism greater than 2.50 diopters (D) (mean 5.54
      D) had implantation of a Staar toric IOL combined with AK. RESULTS: All eyes had
      less than 1.00 D of refractive astigmatism postoperatively. Sixty-nine percent
      achieved an uncorrected visual acuity of 20/40 or better, and no patient lost
      best corrected visual acuity. CONCLUSIONS: Implanting a toric IOL in patients
      with high astigmatism reduced the amount of incisional surgery required.
      Combining techniques can correct all or most of even very high astigmatism (>5.00
      D) while avoiding induced corneal irregularities.

PMID- 12231317
TI  - Long-term endothelial changes in phakic eyes with posterior chamber intraocular
      lenses.
AB  - PURPOSE: To evaluate the long-term endothelial cell changes in phakic eyes after
      implantation of a posterior chamber phakic intraocular lens to correct high
      ametropia. SETTING: Department of Ophthalmology, University Hospital of Vienna,
      Vienna, Austria. METHODS: Thirty-four eyes of 21 patients having implantation of
      an implantable contact lens (ICL, Staar Surgical) for high myopia or hyperopia
      were prospectively examined. The minimum follow-up was 2 to 4 years. Preoperative
      and serial postoperative specular microscopy (Noncon Robo SP 8000, Konan) was
      performed to evaluate the long-term endothelial cell changes. RESULTS: The mean
      preoperative endothelial cell density was 2854 cells/mm(2). The mean endothelial
      cell loss from preoperatively was 1.8% at 3 months, 4.2% at 6 months, 5.5% at 12
      months, 7.9% at 2 years (n = 34), 12.9% at 3 years (n = 13), and 12.3% at 4 years
      (n = 11). All other endothelial cell characteristics remained stable during the 4
      year follow-up. CONCLUSIONS: Continuous endothelial cell loss was observed after
      ICL implantation during a 4-year follow-up. There was rapid cell loss until 1
      year postoperatively, after which the rate of loss was no longer statistically
      significant. The percentage of hexagonal cells (polymorphism) and the coefficient
      of variation (polymegethism) remained stable during the 4-year follow-up.

PMID- 12231318
TI  - Corneal and total optical aberrations in a unilateral aphakic patient.
AB  - PURPOSE: To measure corneal and total optical aberrations in the normal and
      treated eye of a unilateral aphakic patient to (1) cross-validate techniques in
      an eye in which corneal and total aberrations should be almost identical (aphakic
      eye) and (2) compare the interactions of corneal and internal aberrations in the
      normal eye with those in the aphakic eye. SETTING: Instituto de Optica, Consejo
      Superior de Investigaciones Cientificas, Madrid, Spain. METHODS: Aberrations in
      both eyes of a unilateral aphakic patient were measured using laser ray tracing.
      Corneal aberrations were obtained from corneal elevation data measured with a
      corneal videokeratoscope (Humphrey Instruments) using custom software that
      performs virtual ray tracing on the measured front corneal surface. RESULTS:
      There was a 98.4% correspondence between the total and corneal aberration pattern
      in the aphakic eye (6.5 mm pupil). In the normal eye, the total spherical
      aberration was much lower than the corneal spherical aberration; this did not
      occur in the aphakic eye. CONCLUSIONS: The posterior corneal surface contributed
      slightly to the aberrations in the normal cornea (2% at most). The crystalline
      lens appears to play a compensatory role in the total spherical aberration in
      normal eyes.

PMID- 12231319
TI  - Role of intraocular pressure measurement on the day of phacoemulsification
      cataract surgery.
AB  - PURPOSE: To determine whether measurement of intraocular pressure (IOP)
      preoperatively or in the early postoperative period is an accurate predictor of
      raised IOP 24 hours after cataract surgery. SETTING: Department of Ophthalmology,
      Queen's Medical Centre, Nottingham, United Kingdom. METHODS: This prospective
      study comprised 101 eyes of 101 patients having phacoemulsification cataract
      surgery. The IOP was measured by Goldmann applanation tonometry preoperatively
      and 2 to 3 hours, 6 to 8 hours, and 22 to 24 hours postoperatively. The
      relationship between the same-day and next-day IOP readings was examined.
      RESULTS: One hundred patients completed the study. The IOP at 22 to 24 hours was
      significantly correlated with the IOP preoperatively (correlation coefficient [r]
      0.54; 95% confidence interval [CI], 0.38-0.67) and at 6 to 8 hours (r = 0.56; 95%
      CI, 0.41-0.68). In contrast, the IOP measurement at 2 to 3 hours correlated
      relatively poorly with the next-day IOP (r = 0.33; 95% CI, 0.14-0.49). Twelve
      patients had an IOP of 26 mm Hg or higher at 22 to 24 hours. The risk of this
      outcome increased significantly with higher IOP values preoperatively and, to a
      lesser extent, with a raised IOP at 6 to 8 hours. Glaucoma and ocular
      hypertension were associated with a 2.9-fold increased risk (95% CI, 0.67-12.8)
      of a next-day IOP of 26 mm Hg or higher. CONCLUSIONS: Preoperative IOP or a
      diagnosis of glaucoma or ocular hypertension were significant risk factors for
      raised next-day IOP after small-incision phacoemulsification. It may be possible
      to select patients at greater risk of prolonged ocular hypertension before
      surgery for prophylactic IOP-lowering treatment. This would minimize patient
      morbidity and reduce the number of patients requiring next-day review, resulting
      in significant health economic savings.

PMID- 12231320
TI  - Pupillary capture after combined management of cataract and vitreoretinal
      pathology.
AB  - PURPOSE: To report the incidence, pathogenesis, and management of pupillary
      capture after combined phacoemulsification with intraocular lens (IOL)
      implantation and vitreoretinal surgery. SETTING: Oxford Eye Hospital, The
      Radcliffe Infirmary, Oxford, United Kingdom. METHODS: This retrospective case
      review comprised 12 patients who developed pupillary capture after combined
      phacoemulsification, IOL implantation, and pars plana vitrectomy (PPV). Eleven
      IOLs were implanted in the capsular bag, and 1 was sulcus fixated. All patients
      had a long-acting gas tamponade and were advised to lie face down
      postoperatively. All patients subsequently had IOL repositioning using a bimanual
      technique. RESULTS: The incidence of pupillary capture was 8.95% and occurred a
      mean of 3.25 weeks postoperatively. At least 6 clock hours of the pupillary
      margin were captured by the optic except in 1 case in which the pupillary capture
      was total. Half the patients had posterior capsule opacification that required a
      neodymium:YAG laser capsulotomy after IOL repositioning. CONCLUSIONS: The
      incidence of pupillary capture after combined phacoemulsification, IOL
      implantation, PPV, and injection of long-acting gas was high. This complication
      can be minimized by creating a smaller capsulorhexis, having the patient maintain
      a strict face-down position, securing wound closure, and injecting an air bubble
      into the air chamber to push the iris-lens diaphragm posteriorly.

PMID- 12231321
TI  - Changes in the area of the anterior capsule opening after intraocular lens
      implantation.
AB  - PURPOSE: To evaluate the reduction rate of the area of the anterior capsule
      opening after continuous curvilinear capsulorhexis (CCC) with 3 types of
      intraocular lenses (IOLs). SETTING: St. Mary's Hospital, The Catholic University
      of Korea, Seoul, Korea. METHODS: Sixty-five eyes of 51 patients having
      phacoemulsification and IOL implantation were assigned to 1 of 3 groups based on
      type of IOL: 1-piece acrylic (n = 16), 3-piece acrylic (n = 26), or silicone (n =
      23). The area of the anterior capsule opening was measured 1 day and 1, 2, 3, 6,
      and 12 months postoperatively. RESULTS: There was significant reduction in the
      area of the anterior capsule opening 1 day to 3 months postoperatively in all 3
      groups (P <.001). There was no further reduction after 3 months in any group. The
      reduction in the area of the anterior capsule opening was significantly less in
      both acrylic IOL groups than in the silicone IOL group at 3 months (P =.040) and
      12 months (P =.023); however, there was no significant difference between the 2
      types of acrylic IOLs (P =.933). CONCLUSIONS: Although there was a reduction in
      the area of the anterior capsule opening in all patients, the amount was
      significantly less in the 2 acrylic IOL groups than in the silicone IOL group.
      This should be considered when selecting an IOL, especially for eyes at risk for
      capsule contraction.

PMID- 12231322
TI  - Sulcus implantation of a 3-piece, 6.0 mm optic, hydrophobic foldable acrylic
      intraocular lens in phacoemulsification complicated by posterior capsule rupture.
AB  - To evaluate the safety of implanting a 3-piece, 6.0 mm optic, foldable acrylic
      intraocular lens (IOL) in cases of posterior capsule rupture during
      phacoemulsification. Department of Ophthalmology, Ahepa Hospital, Aristotle
      University Medical School, and Interbalkan Medical Center, Thessaloniki, Greece.
      This prospective noncomparative case series included 28 eyes (28 patients) having
      phacoemulsification complicated by extensive posterior capsule rupture with or
      without vitreous loss. In all eyes, a 3-piece, 6.0 mm optic, foldable acrylic IOL
      (AcrySof MA60BM, Alcon) was implanted in the sulcus. Postoperative examination
      included best corrected visual acuity (BCVA), anterior segment biomicroscopy, IOL
      centralization and position, intraocular pressure (IOP), and fundus
      biomicroscopy. The follow-up was 6 months. The most common postoperative
      complications were transient corneal edema in 12 eyes and increased IOP in 11
      eyes. Slight asymptomatic decentralization from the center of the pupil (1.0 to
      2.0 mm) and pseudophacodonesis were observed in 5 eyes each. Friction of the IOL
      with the iris occurred in 1 eye. Clinically significant cystoid macular edema
      occurred in 3 eyes. The final BCVA was between 20/15 and 20/25 in 18 patients,
      20/30 in 2, between 20/40 and 20/50 in 4, and between 20/60 and 20/200 in 4.
      AcrySof IOL implantation in the sulcus during phacoemulsification complicated by
      posterior capsule rupture preserved the advantages of small-incision surgery. The
      postoperative behavior and centralization of the IOLs resembled those of
      poly(methyl methacrylate) lenses.

PMID- 12231323
TI  - Effect of hydrodissection on intraoperative performance: randomized study.
AB  - PURPOSE: To evaluate the effect of hydrodissection on intraoperative performance
      during phacoemulsification of age-related nuclear cataracts. SETTING: Iladevi
      Cataract & IOL Research Centre, Ahmedabad, India, and Center for Research on
      Ocular Therapeutics and Biodevices, Storm Eye Institute, Medical University of
      South Carolina, Charleston, South Carolina, USA. METHODS: In a prospective study,
      86 eyes were randomly assigned to have multiquadrant hydrodissection (+HD, n =
      48) or no hydrodissection (-HD, n = 38) during phacoemulsification of a grade 1
      to 3 nuclear cataract. Excluded were patients with grade 4 or 5 nuclear
      sclerosis, a poorly dilating pupil, or associated ocular/systemic disease.
      Parameters assessed were nucleus and cortex removal time, the amount of fluid
      used for cortex removal, and the total amount of fluid used. The ease of nucleus
      rotation and cortical cleanup was also evaluated and graded subjectively as very
      easy, difficult, or very difficult. Data were analyzed using the Student t test
      and the chi-square test. RESULTS: The mean nucleus removal time was 355 seconds
      +/- 237 (SD) and 474 +/- 212 seconds in the +HD and -HD groups, respectively (P
      =.09). The mean cortex removal time was significantly less in the +HD group than
      in the -HD group (79 +/- 51 seconds and 220 +/- 222 seconds, respectively) (P
      =.007). Significantly less fluid (43%) was used for cortex removal in the +HD
      group than in the -HD group (mean 70 +/- 45 mL and 123 +/- 82 mL, respectively)
      (P =.013), and significantly less total fluid (35%) was used in the +HD group
      (312 +/- 132 mL and 422 +/- 80 mL, respectively) (P =.002). Nucleus rotation was
      easy in all eyes in the +HD group; 68.43% of eyes in the -HD group failed to
      achieve rotation (P =.001). Cortex removal was very easy in 52.08% of eyes in the
      +HD group and easy in 47.90%; it was easy in 52.63% in the -HD group, difficult
      in 36.84%, and very difficult in 10.52%. CONCLUSION: The use of multiquadrant
      cortical-cleaving hydrodissection made removal of the lens nucleus and cortex
      easier and faster during phacoemulsification of age-related nuclear cataracts.

PMID- 12231324
TI  - Corneal optical coherence tomography before and after phototherapeutic
      keratectomy for recurrent epithelial erosions(2).
AB  - PURPOSE: To study the representation of corneal structures with optical coherence
      tomography (OCT) before and after excimer laser phototherapeutic keratectomy
      (PTK) for recurrent epithelial erosions. SETTING: Departments of Ophthalmology,
      Vivantes Klinikum Neukolln, Berlin, and Medizinische Universitat, Lubeck,
      Germany. METHODS: This prospective study comprised 15 eyes of 14 patients with
      recurrent epithelial erosions. The central corneal and epithelial thickness as
      well as the wound-healing response in the anterior corneal stroma were assessed
      with slitlamp-adapted OCT before and after PTK. RESULTS: After PTK, the symptoms
      improved in all patients without loss of best corrected, glare, or low-contrast
      visual acuity. The mean central corneal OCT thickness was 540 microm +/-28 (SD)
      preoperatively, 492 +/- 36 microm immediately after epithelial debridement and
      PTK, and 519 +/- 25 microm after 7 weeks (P <.01). The mean central epithelial
      OCT thickness changed from 70 +/- 13 microm preoperatively to 60 +/- 7 microm
      after 7 weeks (P >.01). Changes in the light-scattering properties in the
      anterior subepithelial stroma revealed a hyperreflective area with a mean
      thickness of 46 +/- 13 microm after 7 weeks. CONCLUSIONS: Using noncontact
      corneal OCT, corneal and epithelial thickness changes and the wound-healing
      response in the anterior corneal stroma could be evaluated after PTK in patients
      with recurrent epithelial erosions.

PMID- 12231325
TI  - Vector summation of anterior and posterior corneal topographical astigmatism.
AB  - PURPOSE: To determine whether vector addition of posterior corneal astigmatism
      improves the correlation between topographical and refractive astigmatism.
      SETTING: Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston,
      Massachusetts, USA. METHODS: Orbscan topographical maps of 40 eyes (31 patients)
      showing 1.0 to 6.0 diopters (D) of astigmatism were analyzed. Topographical
      anterior and posterior corneal surface astigmatism was determined. Refractive
      astigmatism was compared to topographical astigmatism using 3 methods: anterior
      topographical astigmatism, overall topographical astigmatism obtained by vector
      summation of anterior and posterior topographical astigmatism, and simulated
      keratometry (SimK). RESULTS: Refractive astigmatism ranged from 0.25 to 5.00 D.
      The mean error in magnitude between topographical and refractive astigmatism was
      significantly smaller with the overall topographical method (1.06 D +/- 0.92
      [SD]) than the anterior topographical method (1.37 +/- 1.04 D) (P <.0001). The
      mean error in axis between topographical and refractive astigmatism was smaller
      with the overall topographical method (10.4 +/- 13 degrees) than with the
      anterior topographical method (15.5 +/- 30.6 degrees) and with SimK (13.3 +/-
      15.1 degrees), but these differences were not statistically significant.
      CONCLUSION: Consideration of the Orbscan measurement of posterior corneal surface
      toricity may improve the prediction of the magnitude of refractive astigmatism.

PMID- 12231326
TI  - Topography-based screening for previous laser in situ keratomileusis to correct
      myopia.
AB  - PURPOSE: To demonstrate the feasibility of developing a screening tool based on
      corneal topography to detect previous myopic laser in situ keratomileusis
      (LASIK). SETTING: Clinical data from a private clinic analyzed in a university
      setting. METHODS: Two hundred thirty-three topographies were randomly selected so
      1 topography per patient was used: 150 from unoperated corneas and 83 from
      corneas that had LASIK to correct myopia. The mean surgical correction was -4.40
      diopters (D) +/- 2.53 (SD) (range -11.00 to -0.38 D). All topographies were
      performed using an Orbscan II unit (Bausch & Lomb Surgical). The LASIK procedures
      were performed using a Technolas 217C excimer laser and a Hansatome microkeratome
      (Bausch & Lomb Surgical). The algorithms used the mean value of the directional
      derivative (DT) of the anterior tangential curvature of the cornea in the 2.2 mm
      radius central disk and the mean value of the anterior elevation (E) with respect
      to the best-fit sphere in the 0.5 mm radius central disk. Topographies in the
      testing set (n = 119) were classified as operated if E < 0 (E algorithm) or DT >
      0 (DT algorithm) or as unoperated. RESULTS: The E algorithm yielded 0% false
      positives and 16.7% false negatives and the DT algorithm, 6.5% and 7.1%,
      respectively. For myopia greater than -1.12 D, the DT algorithm provided a 0%
      false negative rate. The performance of E and DT algorithms, used in combination,
      was superior to clinical assessment. CONCLUSION: Criteria based on Orbscan II
      corneal topography are proposed for the detection of previous myopic LASIK
      performed with a Technolas 217C excimer laser.

PMID- 12231327
TI  - Decreased incidence of epithelial defects during laser in situ keratomileusis
      using intraoperative nonpreserved carboxymethylcellulose sodium 0.5% solution.
AB  - PURPOSE: To evaluate the incidence of epithelial defects that occur with laser in
      situ keratomileusis (LASIK) using nonpreserved carboxymethylcellulose sodium 0.5%
      solution (Refresh Plus(R)) intraoperatively. SETTING: Community-based refractive
      center. METHODS: This retrospective study comprised 105 patients (210 eyes) who
      had primary bilateral LASIK by 1 of 2 surgeons between October 1 and December 1,
      2000. The 114 eyes treated subsequent to November 1, 2000, received Refresh Plus
      intraoperatively, and the 96 eyes treated before this date did not. The incidence
      of epithelial defects and diffuse lamellar keratitis (DLK) in both groups was
      recorded. The preoperative keratometry measurements of all cases were also
      recorded. RESULTS: There was a statistically significant decrease in the
      incidence of epithelial defects in the group that received Refresh Plus
      intraoperatively (P =.02). No statistically significant between-group difference
      in the incidence of DLK was detected. Analysis of the keratometry measurements
      revealed no statistically significant association between the amount or axis of
      astigmatism and the incidence of epithelial defects or DLK. CONCLUSION: The
      intraoperative use of nonpreserved Refresh Plus significantly decreased the rate
      of epithelial defects that occurred during LASIK.

PMID- 12231328
TI  - Clinical evaluation of refraction using a handheld wavefront autorefractor in
      young and adult patients.
AB  - PURPOSE: To determine the accuracy of measurement by the SureSight autorefractor
      (software version 2.0) and the influence of accommodation. SETTING: Pediatric
      Section, Department of Ophthalmology, University of Hamburg, Hamburg, Germany.
      METHODS: In a series of comparative measurements, autorefractor readings were
      compared with cycloplegic retinoscopy in 195 eyes of 108 patients (1 to 81 years)
      measured under cycloplegia. Ninety-six eyes were also measured without
      cycloplegia. RESULTS: The wavefront autorefractor was able to refract human eyes
      from a distance of 0.35 m. The accuracy was lower than that with conventional
      tabletop autorefractors. A difference of less than 0.51 diopter (D) was found in
      68% of the spherical equivalents under cycloplegia. Many emmetropic and hyperopic
      children accommodated during the noncycloplegic measurements and were minus
      overcorrected up to -6.13 D. In our group of young patients (2 to 17 years), 47%
      were minus-overcorrected by more than -2.00 D. CONCLUSIONS: The wavefront
      autorefractor uses a new method to determine the refractive state of the eye from
      a distance. It was less accurate than other conventional autorefractors. A
      benefit is its application in infants and disabled and uncooperative subjects.
      Cycloplegia is necessary in young hyperopic patients.

PMID- 12231329
TI  - Corneal impact of ultrasound and bevel position in phacoemulsification.
AB  - PURPOSE: To investigate the amplitude of ultrasound waves that reach the cornea
      with the phacoemulsification tip at different angles. SETTING: Institute for
      Applied Mechanics and Control Engineering, University of Siegen, Siegen, Germany.
      METHODS: A model eye was constructed with an ultrasound tip (angle 45 degrees) in
      the typical position during the procedure and a sensor mounted in the apex of the
      artificial cornea. The sensor measured the incoming ultrasound waves. Thirty
      bursts of ultrasound energy were set at 100% power with the bevel of the tip
      facing up toward the cornea, and 30 bursts were set with the bevel facing down
      toward the lens. RESULTS: There was no statistically significant difference in
      the measurements with the tips bevel up and bevel down. CONCLUSIONS: There was no
      significant difference in the corneal load from ultrasound waves with the
      phacoemulsification tip in a bevel-up or bevel-down position.

PMID- 12231330
TI  - Frozen cultured sheets of epidermal keratinocytes in reepithelialization and
      repair of the cornea after photorefractive keratectomy.
AB  - PURPOSE: To determine whether frozen cultured sheets of human allogeneic
      epidermal keratinocytes (CEAK) improved wound repair after experimental corneal
      ablation by photorefractive keratectomy (PRK). SETTING: Hospital "Luis Sanchez
      Bulnes" de la Asociacion para Evitar la Ceguera en Mexico, I.A.P, and Department
      of Cell Biology, CINVESTAV-IPN, Mexico City, Mexico. METHODS: Transepithelial PRK
      was performed in the right eye of male albino rabbits to obtain a 112 microm deep
      and 6.0 mm diameter ablation zone. In 17 eyes, the ablations were covered with
      frozen CEAK; in 11 eyes, the ablations were covered with a disposable contact
      lens without the cultured sheets; and in the control group (13 eyes), the
      ablations were not covered. Subepithelial fibrosis and reepithelialization of the
      ablated zone were evaluated in serial paraffin-embedded tissue sections from all
      wounds. RESULTS: Treatment with CEAK reduced fibroblast proliferation and the
      inflammatory response beneath the ablated zone and produced better organization
      of the newly formed epithelium by eliminating significant hyperplasia or
      discontinuities in the periodic acid Shiff-stained basement membrane. It also led
      to accelerated reepithelialization. CONCLUSIONS: The use of frozen CEAK as a
      biologically active wound dressing improved tissue repair at 1 month in corneas
      ablated by transepithelial PRK in the male albino rabbit model. Treatment with
      CEAK could improve the outcome of PRK in humans.

PMID- 12231331
TI  - Practice styles and preferences of ASCRS members--2001 survey.
AB  - A survey of the practice styles and preferences of members of the American
      Society of Cataract and Refractive Surgery (ASCRS) with a United States ZIP code
      was performed in August 2001. Approximately 20% (1130) of the 5686 questionnaires
      mailed were returned before the November cutoff date. The response rate was
      undoubtedly negatively affected by the September 11 attack on the World Trade
      Center in New York. Three profile questions were used to cross-tabulate: age of
      the ophthalmologist, geographic location, and volume of cataract surgery per
      month. Data in this survey were compared with those in previous surveys of ASCRS
      members.

PMID- 12231332
TI  - Spontaneous posterior dislocation of intraocular lenses fixated in the capsular
      bag.
AB  - We report 4 cases of complete posterior dislocation of an intraocular lens (IOL)
      in the capsular bag occurring a mean of 5.5 years after uneventful cataract
      surgery. In all 4 cases, posterior chamber IOLs were fixated within the
      capsulorhexis. The patients experienced sudden loss of vision without an episode
      of trauma or ocular disease. Using a 3-port pars plana vitrectomy, the IOLs were
      explanted through a limbal incision and a new IOL was sutured to the ciliary
      sulcus. Histological examination indicated that zonular fibers were severed at
      the site of insertion in the capsule.

PMID- 12231334
TI  - Oculocardiac reflex in a nonsedated laser in situ keratomileusis patient.
AB  - A healthy 21-year-old man had laser in situ keratomileusis (LASIK) in the right
      eye for a refractive error of -7.0 diopters. The electrocardiogram findings and
      heart rate were recorded before LASIK; during eye lid speculum insertion, vacuum
      application, corneal flap preparation, and excimer laser keratectomy; and after
      the procedure. The pre-LASIK heart rate was 90 pulses/min. Severe bradycardia of
      40 beats/min developed during vacuum application, and the procedure was
      terminated. Severe bradycardia caused by an oculocardiac reflex may occur during
      LASIK, and patients should be closely monitored during the procedure.

PMID- 12231333
TI  - Diplopia following sub-Tenon's infiltration of local anesthesia.
AB  - A series of 3 patients with persistent diplopia following sub-Tenon's local
      anesthesia is presented. All 3 patients showed a pattern of vertical diplopia
      consistent with restriction of the inferior rectus muscle. The pathogenesis and
      significance of this complication are discussed.

PMID- 12231335
TI  - Extensive corneal epithelial defect associated with internal hordeolum after
      uneventful laser in situ keratomileusis.
AB  - This report illustrates a retrospective case review in which extensive corneal
      epithelial ulceration occurred concomitantly with an internal hordeolum in the
      inferior forniceal conjunctiva 24 hours after an uneventful laser in situ
      keratomileusis. The internal hordeolum and epithelial defect were successfully
      managed using a bandage soft contact lens, a course of topical dexamethasone and
      tobramycin, and generous lubrication.

PMID- 12231336
TI  - Repair of Descemet's membrane detachment after viscocanalostomy.
AB  - We report an alternative descemetopexy technique in a case of Descemet's membrane
      detachment after viscocanalostomy, possibly caused by high-molecular-weight
      viscoelastic material.

PMID- 12231337
TI  - Erroneous automated refraction in a case of asteroid hyalosis.
AB  - To our knowledge, this is the first report of asteroid hyalosis giving rise to
      spurious automated refraction readings. A patient with asteroid hyalosis had
      uneventful phacoemulsification with intraocular lens implantation. Using a Nikon
      autorefractor, the postoperative refraction was +13.0 diopters (D); retinoscopy
      revealed that it should be +1.0 D. Asteroid hyalosis changes the optical quality
      of the vitreous and can cause an incorrect reading from automated equipment such
      as autorefractors and A-scan ultrasound scanners. In patients with asteroid
      hyalosis, results from autorefractors should be viewed in conjunction with
      clinical findings.

PMID- 12231338
TI  - Effect of single- and double-running sutures on corneal astigmatism and suture
      loosening after PKP.

PMID- 12231339
TI  - Phakonit. cataract removal through a sub-1.0 mm incision and implantation of the
      ThinOptX rollable intraocular lens.

PMID- 12231340
TI  - Trypan-blue-stained viscoelastic material for ophthalmic surgery.

PMID- 12231341
TI  - Acrylic lens exchange for late opacification of the optic.

PMID- 12231342
TI  - Role of the bandage contact lens in the management of concomitant
      keratoconjunctivitis medicamentosa and cystoid macular edema.

PMID- 12231346
TI  - Claudin-based barrier in simple and stratified cellular sheets.
AB  - For homeostasis in multicellular organisms, isolation and compartmentalisation of
      the internal environment are essential, and are established by various cellular
      sheets. For these cellular sheets to function as barriers, the intercellular
      route must be sealed. Recent advances reveal that claudins - major cell adhesion
      molecules in tight junctions - are directly involved in this intercellular
      sealing, not only in simple but also in stratified cellular sheets in
      vertebrates.

PMID- 12231347
TI  - Desmosomal cadherins.
AB  - New evidence from blocking desmosomal adhesion with anti-adhesion peptides
      reveals a role for desmosomes in cell positioning in morphogenesis. Desmosomal
      adhesion is necessary for the stability of adherens junctions in epithelial cell
      sheets. Knockout and mis-expression of desmosomal cadherins in mice suggests that
      they may function directly or indirectly in regulating epidermal differentiation.
      Protein kinase C signalling and tyrosine phosphorylation appear to regulate
      desmosomal adhesion. There are new insights into the role of desmosomal cadherins
      in autoimmune, infectious and genetic disease.

PMID- 12231348
TI  - Cell-cell adhesion and signalling.
AB  - Signalling pathways activated by Rho small GTPases have recently been identified
      that coordinate junction assembly, stability and function, as well as
      interactions of adhesive complexes with the underlying cortical cytoskeleton.
      Particularly exciting is the interplay between adherens junctions, activation of
      Rho proteins and the dynamics of microtubule, actin and intermediate filaments.
      This interplay has important implications for functional regulation of cell-cell
      adhesion, and points to a more integrated view of signalling processes.

PMID- 12231350
TI  - The polarising role of cell adhesion molecules in early development.
AB  - Polarising a cell or an embryo is a crucial and recurrent event during
      development, as it is important for cell differentiation and migration. Cells can
      become polarised along their apical-basal axis and also within the plane of the
      tissue layer to which they belong. The embryo develops three axes: the
      anteroposterior, the dorsoventral and the left-right axis. Recent work indicates
      instructive roles for cell adhesion molecules in establishing not only apical
      basal polarity but also planar cell polarity and, surprisingly, in the generation
      of left-right asymmetry in vertebrates. Signalling cascades that regulate
      polarity formation seem to be conserved among different organisms, thereby
      raising the intriguing question of whether this also holds true for the cell
      adhesion molecules.

PMID- 12231349
TI  - Protocadherins.
AB  - Protocadherins constitute the largest subgroup within the cadherin family of
      calcium-dependent cell-cell adhesion molecules. Recent progress in genome
      sequencing has enabled a refined phylogenetic analysis of protocadherins and led
      to the discovery of three large protocadherin clusters on human chromosome
      5/mouse chromosome 18. Interestingly, many of the circa 70 protocadherins in
      mammals are highly expressed in the central nervous system. Roles in tissue
      morphogenesis and formation of neuronal circuits during early vertebrate
      development have been inferred. In the postnatal brain, protocadherins are
      possibly involved in the modulation of synaptic transmission and the generation
      of specific synaptic connections.

PMID- 12231351
TI  - Epithelial fusions in the embryo.
AB  - Morphogenesis in the embryo involves the bending, folding and fusing of
      epithelial tissues to create the final complex shapes of the various organs and
      structures in the body. One essential process that occurs frequently during
      development is the drawing together and fusion of epithelial edges. Drosophila
      dorsal closure is perhaps the most genetically tractable of this type of
      movement, and several recent advances have revealed much about the signals
      regulating the dynamic actin cytoskeletal machineries that underlie the zippering
      closed of this hole in the embryonic fly. It is now clear that there are
      intriguing parallels with more complex morphogenetic tissue movements in
      vertebrates.

PMID- 12231352
TI  - T-cell activation: a multidimensional signaling network.
AB  - Naive T cell activation requires the interactions of antigen receptors, adhesion
      molecules and co-stimulatory molecules. Antigen receptors and adhesion molecules
      are involved in spatio-temporal movement to form a stable immunological synapse.
      This stable junction interrupts T cell migration, and provides a platform for
      temporally regulated co-stimulatory receptor signaling spanning a period of days.

PMID- 12231353
TI  - Selectins: lectins that initiate cell adhesion under flow.
AB  - Interactions of selectins with cell-surface glycoconjugates mediate tethering and
      rolling adhesion of leukocytes and platelets on vascular surfaces. Recent studies
      have helped elucidate the molecular details of selectin-ligand interactions, the
      biosynthetic pathways for constructing selectin ligands, and the biophysical and
      cell biological features that modulate selectin-dependent rolling under flow.

PMID- 12231354
TI  - Regulation of endothelial cell contacts during leukocyte extravasation.
AB  - The molecular mechanisms that control the opening and formation of endothelial
      cell contacts are of central importance for leukocyte extravasation, endothelial
      permeability and angiogenesis. Progress has been made in identifying novel
      membrane proteins at endothelial cell contacts as well as novel mechanisms that
      control interendothelial adhesiveness and transendothelial migration of
      leukocytes.

PMID- 12231355
TI  - Integrin signaling: it's where the action is.
AB  - Recent advances highlight a critical role for integrin receptors for
      extracellular matrix in determining where in cells critical signals are
      transduced. Integrins are shown to activate signaling intermediates at specific
      surface membrane locations, to promote nuclear translocation of factors that
      activate gene transcription, and to recruit and augment the signaling power of
      receptors for growth factors.

PMID- 12231356
TI  - Integrin-associated proteins.
AB  - A diverse group of plasma membrane proteins have been found associated with
      integrins in supramolecular complexes. These associated plasma membrane molecules
      can modulate virtually all integrin functions by altering signal transduction
      arising from integrin ligation. In the past two years, new examples of signaling
      through heterotrimeric G proteins and regulation by membrane rafts have
      emphasized their importance in the function of integrin-containing supramolecular
      complexes.

PMID- 12231357
TI  - Matricellular proteins: extracellular modulators of cell function.
AB  - The term 'matricellular' has been applied to a group of extracellular proteins
      that do not contribute directly to the formation of structural elements in
      vertebrates but serve to modulate cell-matrix interactions and cell function. Our
      understanding of the mode of action of matricellular proteins has been advanced
      considerably by the recent elucidation of the phenotypes of mice that are
      deficient in these proteins. In many cases, aspects of these phenotypes have
      illuminated previously unsuspected consequences of the lack of appropriate
      interactions of cells with their environment.

PMID- 12231358
TI  - Versican: a versatile extracellular matrix proteoglycan in cell biology.
AB  - Versican is a large extracellular matrix proteoglycan that is present in a
      variety of tissues. Successful cloning of the gene in man, mouse, cow and chicken
      has revealed the existence of at least four splice variants of versican, which
      differ in the size of the core protein and the number of glycosaminoglycan
      chains. The highly interactive nature of versican provides a basis for its
      importance as a structural molecule, creating loose and hydrated matrices during
      key events in development and disease; and by interacting either directly with
      cells or indirectly with molecules that associate with cells to, in part,
      regulate cell adhesion and survival, cell proliferation, cell migration and
      extracellular matrix assembly. Several studies within the past two years have
      confirmed a significant role for versican in regulating cell phenotype.

PMID- 12231359
TI  - The cell surface: the stage for matrix metalloproteinase regulation of migration.
AB  - Matrix metalloproteinases are important for the turnover of extracellular matrix
      in tissue. Recent studies have expanded their roles well beyond extracellular
      matrix degradation - they also cleave many growth factors, cytokines and cell
      adhesion molecules in the extracellular milieu, modulating their functions
      irreversibly. In particular, some matrix metalloproteinases that associate with
      the cell surface have arisen as intriguing regulators of cellular functions,
      including migration.

PMID- 12231360
TI  - Cell interactions with three-dimensional matrices.
AB  - Signaling and other cellular functions differ in three-dimensional compared with
      two-dimensional systems. Cell adhesion structures can evolve in vitro towards in
      vivo-like adhesions with distinct biological activities. In this review, we
      examine recent advances in studies of interactions of fibroblasts with collagen
      gels and fibronectin-containing matrices that mimic in vivo three-dimensional
      microenvironments. These three-dimensional systems are illuminating mechanisms of
      cell-matrix interactions in living organisms.

PMID- 12231361
TI  - Coming to grips with integrin binding to ligands.
AB  - Integrins are alphabeta heterodimeric cell-surface receptors that are vital to
      the survival and function of nucleated cells. They recognize aspartic-acid- or a
      glutamic-acid-based sequence motifs in structurally diverse ligands. Integrin
      recognition of most ligands is divalent cation dependent and conformationally
      sensitive. In addition to this common property, there is an underlying binding
      specificity between integrins and ligands for which there has been no structural
      basis. The recently reported crystal structures of the extracellular segment of
      an integrin in its unliganded state and in complex with a prototypical Arg-Gly
      Asp (RGD) ligand have provided an atomic basis for cation-mediated binding of
      aspartic-acid-based ligands to integrins. They also serve as a basis for
      modelling other integrins in complex with larger physiologic ligands. These
      models provide new insights into the molecular basis for ligand binding
      specificity in integrins and its regulation by activation-driven tertiary and
      quaternary changes.

PMID- 12231364
TI  - Classification of bronchiolitis obliterans syndrome-taxonomic realism or
      skepticism.

PMID- 12231362
TI  - Genetics of Parkinson's disease and biochemical studies of implicated gene
      products.
AB  - Parkinson's disease was thought, until recently, to have little or no genetic
      component. This notion has changed with the identification of three genes, and
      the mapping of five others, that are linked to rare familial forms of the disease
      (FPD). The products of the identified genes, alpha-synuclein (PARK 1), parkin
      (PARK 2), and ubiquitin-C-hydrolase-L1 (PARK 5) are the subject of intense cell
      biological and biochemical studies designed to elucidate the underlying mechanism
      of FPD pathogenesis. In addition, the complex genetics of idiopathic PD is
      beginning to be unraveled. Genetic information may prove to be useful in
      identifying new therapeutic targets and identifying the preclinical phase of PD,
      allowing treatment to begin sooner.

PMID- 12231365
TI  - The Registry of the International Society for Heart and Lung Transplantation:
      past, present and future.

PMID- 12231366
TI  - The registry of the international society for heart and lung transplantation:
      nineteenth official report-2002.

PMID- 12231367
TI  - Long-term results of cardiac transplantation from live donors: the domino heart
      transplant.
AB  - BACKGROUND: Hearts explanted from the recipients of heart-lung transplants
      provide a unique source of transplants from live donors. This article presents
      long-term results with this procedure at our center. METHODS: We performed a
      retrospective chart review of domino transplantations performed in our
      institution between 1989 and 1998. RESULTS: We analyzed 131 domino transplants
      (123 orthotopic, 8 heterotopic). Domino hearts were from patients with cystic
      fibrosis (69%), primary pulmonary hypertension (15%), and other diagnoses (16%).
      The mean recipient pulmonary vascular resistance (PVR) was 3.1 Wood units, 25% of
      patients having values >4 Wood units. Thirty-day mortality was 13%. The 1-, 5-,
      and 10-year graft survival was 75% (70% confidence interval [CI], 65-74), 70%
      (70% CI, 65-74), and 58% (70% CI, 52-64), respectively. Patients with PVR >4 Wood
      units had 1-year survival (76%; 70% CI, 69-84) similar to that of patients with
      PVR of < or =4 units (74%; 70% CI, 69-80). Recipients of hearts from patients
      with cystic fibrosis survived longer (5-year survival, 76%; 70% CI, 71-82) vs 65%
      for non-cystic fibrosis hearts (70% CI, 57-74) p = 0.09). One-year survival was
      decreased after transplantation of hearts from female donors (66%; 70% CI, 60
      72)) compared with hearts from male donors (85%; 70% CI, 79-90); p = 0.06). Late
      deaths caused by coronary artery disease and malignancy were uncommon.
      CONCLUSION: Although the rate of early mortality after domino transplantation was
      slightly higher than after cadaveric transplantation, we noted a remarkably low
      long-term attrition rate in recipients of domino grafts, up to 10 years. In
      addition, successful transplantation of patients with high PVR supports the
      hypothesis that heart-lung recipients may provide superior donor hearts for this
      patient group, many of whom traditional listing criteria would exclude.

PMID- 12231368
TI  - Reversal of chronic cyclosporine nephrotoxicity after heart transplantation
      potential role of mycophenolate mofetil.
AB  - BACKGROUND: Chronic cyclosporine nephrotoxicity (CCN) after heart transplantation
      is a progressive condition that may lead to end-stage renal failure. The extent
      to which CCN is reversible with reduction or withdrawal of cyclosporine therapy
      is unknown. The aim of this study was to assess the reversibility of CCN and to
      assess the safety and efficacy of a strategy of cyclosporine dosage reduction,
      combined with conversion from azathioprine to mycophenolate mofetil (AZA/MMF
      switch) to maintain immunosuppression. METHODS: An AZA/MMF switch followed by
      cyclosporine dose reduction was undertaken in 30 heart transplant recipients (23
      men, 7 women; mean age, 54 +/- 2 years) with established CCN at a mean of 90 +/-
      9 months after transplantation (range, 17-182 months). The mean maintenance MMF
      dosage was 2.3 +/- 0.1 g/day (n = 28). Mean cyclosporine dosage was decreased
      from 2.3 +/- 0.2 mg/kg/day before AZA/MMF switch to 1.6 +/- 0.2 mg/kg/day.
      RESULTS: Three patients (10%) were withdrawn from MMF, 2 because of diarrhea and
      the third because of severe pneumonia that developed within 2 weeks of AZA/MMF
      switch. All 3 were restabilized with AZA. One patient (4%) experienced acute
      rejection 7 months after AZA/MMF switch. This resolved after an oral pulse of
      prednisolone. Systemic infections occurred in 6 patients within 12 months of
      AZA/MMF switch. Actuarial survival 1 year after AZA/MMF switch was 86% +/- 6%.
      One patient died of infection and 3 of other causes. Serum creatinine
      concentration decreased from 248 +/- 15 micromol/liter before cyclosporine dosage
      reduction to 193 +/- 11 micromol/liter and 206 +/- 19 micromol/liter at 3 and 12
      months after dosage reduction (both p < 0.01 versus baseline, n = 23). Of the 23
      patients who remained on MMF at 12 months, a decrease in serum creatinine was
      documented in 19 (83%). Four patients showed no improvement or showed
      deterioration in renal function, and three of these progressed to end-stage renal
      failure. CONCLUSIONS: Chronic cyclosporine nephrotoxicity has a significant
      reversible component in most patients. A strategy of AZA/MMF switch combined with
      cyclosporine dosage reduction is generally well tolerated and results in short
      term improvement in renal function in most patients. Close vigilance is required
      during the first 12 months after AZA/MMF switch because both acute rejection and
      infection may occur.

PMID- 12231369
TI  - Acute vascular rejection is associated with up-regulation of vitronectin receptor
      (alphavbeta3), increased expression of tissue factor, and activation of the
      extracellular matrix metalloproteinase induction system.
AB  - BACKGROUND: A cascade of inflammatory reactions characterize acute vascular
      rejection after heart transplantation. This study was undertaken to test the
      hypothesis that acute vascular rejection is associated with up-regulation of
      vitronectin receptor (alphavbeta3), increased expression of tissue factor, and
      activation of the extracellular matrix metalloproteinase induction system.
      METHODS: Acute vascular rejection developed in 14 heart transplant recipients
      within 2 weeks of transplantation, confirmed by immunofluorescence (AVR group).
      We compared these patients with 10 transplant recipients who had no evidence of
      acute vascular rejection or peritransplant ischemic injury (control group). We
      evaluated endomyocardial biopsy specimens for alphavbeta3, tissue factor, and
      extracellular matrix metalloproteinase inducer (EMMPRIN). RESULTS: Compared with
      the control group, the AVR group demonstrated evidence of significantly increased
      expression of alphavbeta3 (1.9-fold, p < 0.001), tissue factor (1.8-fold, p <
      0.001), and EMMPRIN (1.5-fold, p < 0.001). All patients in the AVR group received
      plasmapheresis; 11 of 14 patients had evidence of ischemic necrosis on biopsy
      specimens, and 3 of 14 patients experienced hemodynamic compromise and graft
      dysfunction and died within 3 weeks of transplant. Another patient died at 10
      months after transplant. CONCLUSIONS: Acute vascular rejection is associated with
      up-regulation of alphavbeta3, tissue factor, and activation of the matrix
      metalloproteinase induction system, which may contribute to the lethal morbidity
      associated with this disease.

PMID- 12231370
TI  - Comparative study of cyclosporine and tacrolimus vs newer immunosuppressants
      mycophenolate mofetil and rapamycin on coronary endothelial function.
AB  - BACKGROUND: Endothelial dysfunction contributes to the development of intimal
      hyperplasia in transplanted hearts by decreasing the protective effects of
      endothelial-derived nitric oxide. Immunosuppressive drugs may increase the
      dysfunction caused by rejection and further accelerate the development of graft
      coronary vasculopathy. This study compares the effect of cyclosporine and
      tacrolimus vs two newer immunosuppressive drugs, mycophenolate mofetil and
      rapamycin, on coronary endothelial function. METHODS: An in vitro model of drug
      incubation in Krebs-bicarbonate solution (4(o)C, 48 hours) using porcine
      epicardial coronary arteries was developed. Coronary endothelial function studies
      were performed in organ chamber experiments after incubation with cyclosporine
      (10(-4), 10(-7) mol/liter), tacrolimus (10(-4), 10(-7) mol/liter), mycophenolate
      mofetil (10(-4), 10(-7) mol/liter), rapamycin (10(-7), 10(-11) mol/liter), and
      their vehicles to assess effects on G-protein-mediated vasorelaxations leading to
      the release of nitric oxide. RESULTS: Exposure to cyclosporine and mycophenolate
      mofetil was associated with a dose-dependent decrease in endothelium-dependent
      relaxations to serotonin (an agonist that binds to 5-HT1D receptors coupled to Gi
      protein) but no impairment of relaxations to bradykinin (an agonist that binds to
      B2 receptors coupled to Gq-proteins). Exposure to tacrolimus and rapamycin caused
      severe impairment of relaxations to serotonin and a lesser one to bradykinin. We
      observed alterations of relaxations to the calcium ionophore A23187 after
      exposure to mycophenolate mofetil and rapamycin. Exposure to rapamycin and
      mycophenolate mofetil vehicles impaired relaxation to all agonists. CONCLUSIONS:
      These results suggest that cyclosporine and mycophenolate mofetil induce a
      dysfunction of the vasorelaxing properties of the endothelium that may lead to a
      decrease in the protective effects of nitric oxide on the vascular wall but that
      these drugs still have a more favorable vascular profile than do tacrolimus and
      rapamycin. Decreased endothelial function after mycophenolate mofetil and
      rapamycin exposure could be caused by their vehicles.

PMID- 12231371
TI  - Upregulation of PAI-1 is mediated through TGF-beta/Smad pathway in transplant
      arteriopathy.
AB  - BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) is the primary
      physiologic inhibitor of plasminogen activator in vivo. Increased PAI-1
      expression is associated with arteriosclerosis. Transforming growth factor-beta
      (TGF-beta) induces PAI-1 production via Smads. METHODS: In vivo, TGF-beta
      receptors (TbetaRs), Smad2, Smad3, and Smad4, PAI-1, and Smad2 phosphorylation
      were examined by immunohistochemistry in 3 native aortas, 14 rat aortic
      syngrafts, and 19 allografts collected at 15, 30, and 45 days post
      transplantation. In vitro, phosphorylation of Smad2 and induction of PAI-1 mRNA
      in human aortic smooth muscle cells (SMCs) in response to TGF-beta treatment were
      detected by Western blot and by TaqMan real-time RT-PCR, respectively. RESULTS:
      Immunohistochemical staining revealed that vascular parenchymal cells contained
      TbetaRI, TbetaRII, Smad2, Smad3, and Smad4, known signaling transducers for TGF
      beta/Smad pathway, in all samples. Intense staining for phospho-Smad2 was
      observed in 94% of endothelial cells (ECs), 86% of intimal cells, 27% of medial
      SMCs, and 38% of adventitial cells at all 3 time points in all aortic allografts,
      but only in 5% of ECs in syngrafts. PAI-1 immunoreactivity was detected in
      similar number of cells, and from consecutive sections, phospho-Smad2 colocalized
      with PAI-1, in the aortic allografts. Low basal level PAI-1 expression was
      observed in aortic syngrafts and native vessels. Smad2 phosphorylation and time
      dependent PAI-1 induction were detected in cultured SMCs upon TGF-beta treatment.
      CONCLUSIONS: Phospho-Smad2 staining in aortic allografts indicates the activation
      of TGF-beta signaling in allo-transplantation; and co-localization of PAI-1 and
      phospho-Smad2 suggests that PAI-1 upregulation is mediated mainly by TGF
      beta/Smad pathway in aortic allografts.

PMID- 12231372
TI  - The use of (99m)technetium-labeled MCP-1 to assess graft coronary artery disease
      in rat cardiac allografts.
AB  - BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is associated with the
      development of graft coronary artery disease (GCAD) following cardiac
      transplantation. This study assessed whether technetium 99m ((99m)Tc)-labeled MCP
      1 binds its receptors in chronic cardiac transplants and thereby provides a
      potential modality to assess GCAD. METHODS: Allogeneic (PVG-->ACI, n = 9) and
      syngeneic (ACI-->ACI, n = 9) rat heterotopic heart transplants were performed.
      Allograft recipients were treated with 7.5 mg/kg per day of Cyclosporin A for 10
      days until tolerance was achieved. After 90 days, animals were injected
      intravenously with (99m)Tc-MCP-1 and killed after 1 hour. Radioactivity of heart
      tissues was measured and standardized to uptake in the overall blood pool. Two
      dimensional (99m)Tc-MCP-1 uptake (autoradiographs) was imaged by exposing 50
      microm sections on a phosphoimager overnight. ED-1 staining of
      monocyte/macrophages was performed on serial sections. Additional sections were
      stained with elastin von Gieson and hematoxylin. Hearts were scored for luminal
      narrowing and intima/media ratio (I/M) with computerized image analysis. RESULTS:
      Allografts exhibited significantly more luminal narrowing (22.5 +/- 10.7% vs 2.6
      +/- 4.6, p = 0.0005) and higher I/M (0.173 +/- 0.151 vs 0.015 +/- 0.029, p =
      0.0088) than isografts. The ratio of (99m)Tc-MCP-1 uptake in allografts (1.04 +/-
      0.4) was greater than that of isograft controls (0.72 +/- 0.11, p = 0.03). Pixel
      counts of autoradiographs and ED-1-stained sections demonstrated a modest
      correlation between the two (R(2) = 0.50). No significant differences were seen
      in acute rejection scores. CONCLUSION: (99m)Tc-MCP-1 uptake was higher in
      allografts vs isografts and was consistent with a greater degree of GCAD. These
      data demonstrating increased radiopharmaceutical uptake in hearts with GCAD
      provide a foundation for the development of a potentially non-invasive imaging
      assay of this disease process in heart transplantation.

PMID- 12231373
TI  - A limited sampling strategy for the estimation of 12-hour Neoral systemic drug
      exposure in heart transplant recipients.
AB  - BACKGROUND: Therapeutic drug monitoring of cyclosporine in heart transplant
      patients is used to monitor therapy and prevent rejection. Of the various methods
      available for performing therapeutic drug monitoring of cyclosporine, the method
      of limited sampling strategy for area under the concentration-time curve
      profiling has been used most widely recently. The process of identifying sparse
      data points to predict area under the concentration-time curve is essentially a
      variable selection problem, with the variables being the drug concentrations at
      the various timepoints. Although fitting more variables into a model will
      typically allow for a better prediction of area under the concentration-time
      curve, improving the prediction has to be traded-off against the desirability of
      using as few timepoints as possible. The objective of this study was thus to
      formulate a model that would provide a good prediction of area under the
      concentration-time curve based on a limited number of sampling points. METHODS:
      We studied 15 stable heart transplant patients (11 Chinese and 4 Indians). All
      patients were receiving Neoral-based immunosuppression. Whole blood samples for
      area under the concentration-time curve analysis were obtained at the following
      timepoints: pre-dose (C(0h)) and at 1, 2, 3, 4, 6 and 12 hours (C(1h), C(2h),
      C(3h), C(4h), C(6h), C(12h), respectively) post-dose during the first dosing
      interval. The linear trapezoidal rule was used to calculate the area under the
      concentration-time curve (AUC) from time 0 h to 12 h. Various limited sampling
      strategies, as well as Keown's formula, which was derived in renal transplant
      patients and used C(0h) and C(2h), were compared based on their capacity for
      reducing total error squared. RESULTS: C(4h) was found to be the single most
      predictive timepoint and explained 95.3% of AUC(0-12) variation. C(0h) and C(12h)
      explained 60% and 75.7% of the variation in AUC(0-12), respectively. The best 2
      variable model identified by stepwise selection procedures included C(1h) and
      C(4h) as predictors, explaining 97.3% of the variation in total area under the
      concentration-time curve from time 0 h to 12 h. Using Keown's algorithm, the R(2)
      was only 80.9%. CONCLUSION: We recommend using C(1h) and C(4h) as surrogate
      markers of area under the concentration-time curve from time 0 h to 12 h in our
      heart transplant patients. Because C(1h) and C(4h) represent timepoints within
      the zone of highest variability for Neoral's absorption phase, a model
      incorporating these timepoints would be able to explain a greater degree of
      variability associated with the Neoral absorption profile.

PMID- 12231374
TI  - Effects of a bradykinin B(2) receptor antagonist, FR173657, on pulmonary ischemia
      reperfusion injury in dogs.
AB  - BACKGROUND: This study investigated the effects of a bradykinin B(2) receptor
      antagonist, FR173657 (FR), on pulmonary ischemia-reperfusion (I/R) injury.
      METHODS: Twenty-four mongrel dogs were divided into four groups (n = 6 each). In
      Groups I, II and III, FR doses of 33, 100 and 300 nmol/kg per hour, respectively,
      were administered continuously beginning 30 minutes before ischemia and
      continuing for 2 hours after reperfusion. In Group IV, vehicle alone was
      administered. Warm ischemia was induced for 3 hours by clamping the left
      pulmonary artery and veins. Simultaneously, the left stem bronchus was bisected
      and then anastomosed before reperfusion. Fifteen minutes after reperfusion, the
      right pulmonary artery and bronchus were ligated. Left pulmonary vascular
      resistance (L-PVR), cardiac output (CO), arterial oxygen pressure (PaO(2)) and
      the alveolar - arterial oxygen pressure difference (A-aDO2) were measured for 4
      hours after reperfusion. Lung tissue was harvested for wet-to-dry weight ratio
      (WDR) measurements, histopathologic studies and polymorphonuclear neutrophil
      (PMN) counts. Serum thromboxane (TX) B(2), 6-keto-prostaglandin (PG) F(1alpha)
      and leukotriene (LT) B(4) levels were also measured. RESULTS: PaO(2), A-aDO2, L
      PVR and CO were significantly (p < 0.05) improved and WDR was significantly (p <
      0.05) lower in Groups II and III than in Group IV. Histologic tissue edema was
      mild, and PMN infiltration was significantly (p < 0.05) reduced in Groups I, II
      and III compared with Group IV. TXB(2) levels were significantly (p < 0.05) lower
      in Group II than in Group IV, whereas 6-keto-PGF(1alpha) levels were not
      significantly different. LTB(4) levels were significantly (p < 0.05) lower in
      Groups II and III than in Group IV. CONCLUSIONS: FR appears to have a protective
      effect on pulmonary I/R injury stemming from the inhibition of eicosanoid
      release.

PMID- 12231375
TI  - A comparative study of the most widely used solutions for cardiac graft
      preservation during hypothermia.
AB  - BACKGROUND: Reports conflict on the benefits of preservative solutions. We
      investigated the efficacy of the most widely used cardioplegic solutions by
      comparing extracellular solutions such as Celsior solution, St. Thomas Hospital
      solutions 1 and 2 (STH-1, STH-2), the modified University of Wisconsin solution
      (UW-1), Lyon Preservation solution (LYPS) from our laboratory, and intracellular
      solutions such as standard University of Wisconsin solution (UW), Bretschneider
      solution (HTK), Stanford solution (STF), and Euro-Collins solution (EC). METHODS:
      Male rats (n = 110) were randomized into 11 groups: LYPS, Celsior, STH-1, STH-2,
      UW-1, UW, HTK, STF, EC, and normal saline solution groups, and a control group.
      All hearts, except controls, were preserved by cold storage (8 hours at 4 degrees
      C) in the various solutions. We used an isolated non-working-heart model and
      biopsy specimens to assess heart preservation (n = 5/group). RESULTS: Hearts
      stored in the EC and saline solutions had poor left ventricular developed
      pressure (LVDP) x heart rate (HR) (1,407.5 +/- 154 and 1,390 +/- 439 mm Hg/mn,
      respectively). In contrast, hearts stored in LYPS and Celsior had a LVDP x HR
      close to control hearts (31,349 +/- 1,847, 27,620 +/- 1,207, and 36,627 +/- 1,322
      mm Hg/mn, respectively), whereas hearts stored in STH-1, STH-2, UW-1, UW, HTK,
      and STF had intermediate functional response (14,278 +/- 2,176, 12,402 +/- 1,571,
      11,428 +/- 1,629, 11,603 +/- 2,521, 7,045 +/- 537, and 7,086 +/- 1,206 mm Hg/mn,
      respectively). Hearts preserved with STH-2, UW, HTK, STF, EC, and saline solution
      showed significantly increased release of creatine kinase and lactate
      dehydrogenase than did control hearts or hearts preserved in Celsior, LYPS, STH
      1, and UW-1. The energetic charge (EC = [(0.5 adenosine diphosphate + adenosine
      triphosphate) / (adenosine triphosphate + adenosine diphosphate + adenosine
      monophosphate)]) in STH-2, UW, HTK, STF, EC, and saline groups was significantly
      lower (p < 0.05) than in the other groups. CONCLUSION: Extracellular-type
      solutions provided better preservation than did intracellular-type solutions.
      However, UW and UW-1 (intracellular- and extracellular-type solutions) provided
      equivalent preservation of cardiac function. Preservation quality may be
      attributed to calcium, often added to extracellular solutions. Among
      extracellular solutions, Celsior and LYPS solution showed comparable efficacy on
      left ventricular function and seemed to offer better preservation than the other
      solutions tested in this study.

PMID- 12231376
TI  - Preferential involvement of larger vessels in a rat model of diabetes-induced
      graft vasculopathy.
AB  - Using previously described models of diabetes-induced transplant coronary artery
      atherosclerosis (TxCAD), we quantitatively assessed TxCAD using computer-assisted
      morphometric measurements. More than 95% of the evaluated vessels were
      intramyocardial vessels. The first and last tertile of the vessel size
      distribution were evaluated for the presence of TxCAD. Severe TxCAD, defined as a
      luminal occlusion > or =75%, was more prevalent in the larger vessels. We
      observed a differential involvement based on vessel size in diabetes-induced
      TxCAD.

PMID- 12231377
TI  - Regression of gastric lymphoma of mucosa associated with lymphoid tissue (MALT)
      following cardiac transplantation.

PMID- 12231378
TI  - Comparison of the effects of zaleplon, zolpidem, and triazolam at various GABA(A)
      receptor subtypes.
AB  - The pyrazolopyrimidine zaleplon is a hypnotic agent that acts at the
      benzodiazepine recognition site of GABA(A) receptors. Zaleplon, like the hypnotic
      agent zolpidem but unlike classical benzodiazepines, exhibits preferential
      affinity for type I benzodiazepine (BZ(1)/omega(1)) receptors in binding assays.
      The modulatory action of zaleplon at GABA(A) receptors has now been compared with
      those of zolpidem and the triazolobenzodiazepine triazolam. Zaleplon potentiated
      GABA-evoked Cl(-) currents in Xenopus oocytes expressing human GABA(A) receptor
      subunits with a potency that was higher at alpha1beta2gamma2 receptors than at
      alpha2- or alpha3-containing receptors. Zolpidem, but not triazolam, also
      exhibited selectivity for alpha1-containing receptors. However, the potency of
      zaleplon at these various receptors was one-third to one-half that of zolpidem.
      Zaleplon and zolpidem also differed in their actions at receptors containing the
      alpha5 or gamma3 subunit. Zaleplon, zolpidem, and triazolam exhibited similar
      patterns of efficacy among the different receptor subtypes. The affinities of
      zaleplon for [(3)H]flunitrazepam or t-[(35)S]butylbicyclophosphorothionate
      ([(35)S]TBPS) binding sites in rat brain membranes were lower than those of
      zolpidem or triazolam. Furthermore, zaleplon, unlike zolpidem, exhibited
      virtually no affinity for the peripheral type of benzodiazepine receptor.

PMID- 12231379
TI  - Accurate prediction of xanthine oxidase inhibition based on the structure of
      flavonoids.
AB  - The flavonoid family shows a high potential for inhibition of xanthine oxidase.
      Currently, more than 4,000 flavonoids are known. The data of this study indicate
      that a planar structure is necessary for high inhibitory activity towards
      xanthine oxidase. Moreover, the contribution of a hydroxyl conjugate turns out to
      be a constant factor when the natural logarithm of IC(50) values is taken. This
      finding allows us to accurately predict the IC(50) value of any given hydroxyl
      group added to the basic flavone structure towards xanthine oxidase. This new
      method may provide an important research tool for elucidating the role that
      flavonoids may have in radical related diseases.

PMID- 12231380
TI  - Protective effect of verbascoside on 1-methyl-4-phenylpyridinium ion-induced
      neurotoxicity in PC12 cells.
AB  - The neuroprotective effects of verbascoside, one of phenylpropanoid glucoside
      isolated from the Chinese herbal medicine Buddleja officinalis Maxim, on 1-methyl
      4-phenylpyridinium ion (MPP(+)) induced apoptosis and oxidative stress in PC12
      neuronal cells were investigated. Treatment of PC12 cells with MPP(+) for 48 h
      induced apoptotic death as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay and flow cytometry, the activation of
      caspase-3 measured by the caspase-3 activity assay kit, the reduction in
      mitochondrial membrane potential with laser scanning confocal microscopy and the
      increase in the extracellular hydrogen peroxide level. Simultaneous treatment
      with verbascoside markedly attenuated MPP(+)-induced apoptotic death, increased
      extracellular hydrogen peroxide level, the activation of caspase-3 and the
      collapse of mitochondrial membrane potential. These results strongly indicate
      that verbascoside may provide a useful therapeutic strategy for the treatment of
      oxidative stress-induced neurodegenerative disease such as Parkinson's disease.

PMID- 12231381
TI  - Activity of novel 4-PIOL analogues at human alpha 1 beta 2 gamma 2S GABA(A)
      receptors--correlation with hydrophobicity.
AB  - A series of novel 5-(4-piperidyl)-3-isoxazolol (4-PIOL) analogues where the 4
      position of the 3-isoxazolol ring was substituted with groups of different size,
      flexibility, and lipophilicity have been characterised. Their activity as
      agonists and/or antagonists on human alpha(1)beta(2)gamma(2S) GABA(A) receptors
      expressed in Xenopus oocytes was studied using two-electrode voltage clamp
      electrophysiology. Methyl- and ethyl-substituted 4-PIOL analogues were
      characterised as partial agonists since weak agonist responses could be
      potentiated with lorazepam and inhibited by the competitive antagonist 2-(3
      carboxypropyl)-3-amino-6-methoxyphenyl-pyradizinum bromide (SR95531). All larger
      substituents in the 4-position of the 3-isoxazolol ring of 4-PIOL converted the
      compounds into pure competitive antagonists. Additionally, for GABA, 4,5,6,7
      tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), piperidine-4-sulphonic acid (P4S),
      and 5-(4-piperidyl)-3-isothiazolol (thio-4-PIOL), a negative linear correlation
      was found between the agonist efficacy of the compound and the ability of
      lorazepam to potentiate EC(95) responses. Furthermore, a positive linear
      correlation between the lipophilicity of the substituents in the 4-position of
      the 3-isoxazolol ring of 4-PIOL and the antagonist affinity was found. These data
      suggest that the GABA(A) receptor contains a hydrophobic binding pocket at the
      GABA recognition site and that the binding of the 4-PIOL analogues is largely
      determined by the transfer from the aqueous phase to the hydrophobic pocket.

PMID- 12231382
TI  - Up-regulation of Na+-dependent Mg2+ transport by nitric oxide and cyclic GMP
      pathway in renal epithelial cells.
AB  - A putative, Na(+)-dependent Mg(2+) transport pathway controls the intracellular
      free Mg(2+) concentration ([Mg(2+)](i)) in various mammalian cells. The
      characteristics of this Mg(2+) transport pathway have not been clarified. Herein,
      we examined the regulatory mechanism of Na(+)-dependent Mg(2+) efflux in renal
      epithelial NRK-52E cells. Mg(2+) removal from the extracellular bathing solution
      induced an Na(+)-dependent [Mg(2+)](i) decrease in Mg(2+) (5 mM)-loaded cells but
      not in control cells. Amiloride inhibited the [Mg(2+)](i) decrease in a dose
      dependent manner (IC(50) = 3 microM). Similarly, atomic absorption
      spectrophotometry showed that Mg(2+) removal decreased intracellular Mg(2+)
      content, while it increased Na(+) content. Calphostin C (1 microM), a protein
      kinase C inhibitor, and genistein, a tyrosine kinase inhibitor (10 microM),
      blocked the [Mg(2+)](i) decrease. The [Mg(2+)](i) decrease was accompanied by an
      increase in intracellular nitric oxide (NO) and cyclic GMP contents. (E)-4-methyl
      2-[(E)-hydoxyimino]-5-nitro-6-methoxy-3-hexenamide (0.1 mM), an NO donor, and 8
      bromo-cyclic GMP (0.1 mM), a membrane-permeable cyclic GMP analogue, accelerated
      the [Mg(2+)](i) decrease. In contrast, N(G)-monomethyl-L-arginine (L-NMMA, 0.1
      mM), an NO competitive inhibitor, and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1
      one (ODQ, 10 microM), an NO-sensitive guanylate cyclase inhibitor, significantly
      blocked the [Mg(2+)](i) decrease. These results indicate that a decrease in
      extracellular Mg(2+) concentration induces the production of NO and cyclic GMP,
      which leads to the up-regulation of Na(+)-dependent Mg(2+) efflux.

PMID- 12231383
TI  - Hypothermic and antipyretic effects of 3-methyl- and 3-phenyl-5-hydroxy-5
      trichloromethyl-4,5-dihydro-1H-pyrazole-1-carboxyamides in mice.
AB  - The effect of novel pyrazolines, 3-methyl-5-hydroxy-5-trichloromethyl-4,5-dihydro
      1H-pyrazole-1-carboxyamide (MPCA) and 3-phenyl-5-hydroxy-5-trichloromethyl-4,5
      dihydro-1H-pyrazole-1-carboxyamide (PPCA) on body temperature and endotoxin
      induced fever was investigated in mice. The subcutaneous (s.c.) administration of
      1.5 mmol/kg dipyrone, MPCA or PPCA and the intracerebroventricular (i.c.v.)
      administration of 225 nmol dipyrone reduced basal rectal temperature.
      Intracerebroventricular administration of 225 nmol MPCA or PPCA did not alter
      basal rectal temperature. The administration of 0.15 mmol/kg (s.c.) or 25 nmol (5
      microl) dipyrone (i.c.v.), MPCA or PPCA had no effect on basal rectal
      temperature, but reversed lipopolysaccharide-induced fever. These results suggest
      that MPCA and PPCA cause antipyresis, which is similar to that caused by
      dipyrone, and may be useful antipyretic agents.

PMID- 12231384
TI  - Lack of effects of prolonged treatment with phenobarbital or phenytoin on the
      expression of P-glycoprotein in various rat brain regions.
AB  - P-glycoprotein is an ATP-dependent drug transport protein that is predominantly
      found in the apical membranes of various epithelial cell types in the body,
      including the blood luminar membrane of the brain capillary endothelial cells
      that make up the blood-brain barrier. Increased P-glycoprotein expression in the
      blood-brain barrier has been described in epileptogenic brain tissue of patients
      with pharmacoresistant epilepsy, suggesting that overexpression of P-glycoprotein
      may be involved in multidrug resistance of epilepsy. The mechanisms underlying
      the overexpression of P-glycoprotein in brain tissue of epileptic patients are
      not clear. Two antiepileptic drugs, phenobarbital and phenytoin, have been
      reported to up-regulate P-glycoprotein in cell cultures, so that chronic
      treatment with antiepileptic drugs may enhance P-glycoprotein expression in the
      blood-brain barrier. To directly address this possibility, we treated rats with
      phenobarbital or phenytoin over 11 days and subsequently determined expression of
      P-glycoprotein by immunohistochemistry in endothelium and parenchyma of several
      brain regions, including regions of the temporal lobe, which is often involved in
      pharmacoresistant types of epilepsy. Except for a moderate increase in the
      intensity of P-glycoprotein expression in the piriform/parietal cortex and
      cerebellum of phenobarbital-treated rats, no significant P-glycoprotein increases
      were seen after prolonged treatment with phenobarbital or phenytoin in any brain
      region examined. In view of recent findings that seizures lead to a transient
      induction of P-glycoprotein in the brain of rats, it seems reasonable to suggest
      that the overexpression of P-glycoprotein in brain regions of patients with
      intractable epilepsy is a consequence of uncontrolled seizures rather than of
      chronic treatment with antiepileptic drugs.

PMID- 12231385
TI  - Dopamine reuptake inhibition and failure to evoke dyskinesia in MPTP-treated
      primates.
AB  - Nonspecific monoamine reuptake inhibitors reverse motor abnormalities in 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmosets without evoking
      established dyskinesia. However, it is not known whether dopamine reuptake
      inhibition alone explains these actions or whether noradrenaline and/or serotonin
      reuptake blockade also contributes. L-DOPA (12.5 mg/kg, p.o.) rapidly reversed
      the baseline locomotor deficits and motor disabilities, but evoked dyskinesia
      (especially limb chorea) in MPTP-treated common marmosets primed to exhibit
      involuntary movements. In contrast, the selective dopamine reuptake inhibitor 1
      (2-(bis-(4-fluorophenyl)-methoxy)ethyl)-4-(3-phenylpropyl) piperazine
      dihydrochloride (GBR 12909) reversed motor deficits in a dose-dependent manner
      but, unlike L-DOPA, did not evoke established dyskinesia in these animals.
      Therefore, inhibition of dopamine reuptake does not evoke established dyskinesia
      in MPTP-treated primates.

PMID- 12231386
TI  - Adenosine A2A receptors inhibit the N-methyl-D-aspartate component of excitatory
      synaptic currents in rat striatal neurons.
AB  - The effects of the adenosine A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethyl
      amino-5'-N-ethylcarboxamidoadenosine (CGS 21680) on currents mediated by
      excitatory amino acid receptors were examined in rat striatal brain slices. In a
      Mg(2+)-free superfusion medium, CGS 21680 decreased the amplitude of excitatory
      postsynaptic currents (EPSCs) in about 70% of striatal neurons. The inhibitory
      effect of CGS 21680 disappeared both in the presence of the adenosine A(2A)
      receptor antagonist 8-(3-chlorostyryl) caffeine and the NMDA receptor antagonist
      2-amino-5-phosphonopentanoic acid (AP-5). NMDA-induced currents were also
      depressed by CGS 21680 in a subset of striatal cells, whereas alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionate (AMPA)-induced currents were not affected.
      The results suggest that adenosine A(2A) receptor agonists inhibit the NMDA
      component of the EPSC.

PMID- 12231387
TI  - Intrahippocampal infusion of ebselen impairs retention of an inhibitory avoidance
      task in rats.
AB  - Ebselen is a seleno-compound used in the treatment of neurological disorders
      involving the glutamatergic system. Although ebselen is currently used in
      clinical trials, the physiological effects of this seleno-compound are poorly
      known. In this study, we investigated the effects of intrahippocampal infusion of
      ebselen (0.1-3 nmol) in rats submitted to an inhibitory avoidance task. Ebselen
      (1-3 nmol) infused after the training session impaired retention of inhibitory
      avoidance, tested 90 min or 24 h after the training session. Moreover, ebselen
      also impaired the retention when infused 30 min prior to training or 10 min prior
      to test sessions. In summary, ebselen impaired memory consolidation, acquisition
      and retrieval. This amnesic effect of ebselen could be related to oxidant
      activity at N-methyl-D-aspartate (NMDA) receptors. Our results indicate that more
      studies must be performed to investigate the mechanisms of this amnesic effect
      and whether ebselen has a cognition-impairing effect when administered
      chronically.

PMID- 12231388
TI  - Characterization of a new muscarinic receptor antagonist PNU-171990 in guinea
      pig, cat and human smooth muscle.
AB  - The present study was done to characterize a new compound, PNU-171990, 2
      diisopropyl aminoethyl 1-phenylcyclopentane carboxylate hydrochloride, with
      functional smooth muscle selectivity at least as high as tolterodine. In vitro
      homogenates of guinea pig cerebral cortex, parotid gland, heart, urinary bladder,
      and Chinese hamster ovary (CHO) cells expressing human muscarinic m(1)-m(5)
      receptors PNU-171990 did not show selectivity for any subtype (pK(i), 7.72-8.64).
      PNU-171990 caused a parallel shift in the concentration-response curve for
      carbachol-induced contraction of smooth muscle from guinea pig bladder (pK(B),
      7.65), guinea pig ileum (pK(B), 8.48), and human ileum (pK(B), 7.10). In vivo PNU
      171990 inhibited urinary bladder contraction with a significantly lower ID(50)
      than on the salivary secretion (206 and 706 nmol/kg, respectively, P<0.05). In
      conclusion, PNU-171990 is a competitive and potent muscarinic receptor antagonist
      in vitro with a numerically better selectivity ratio for the bladder contraction
      over salivation in vivo than tolterodine.

PMID- 12231389
TI  - Role of endothelin ET(B) receptors in the renal hemodynamic and excretory
      responses to big endothelin-1.
AB  - We determined the role of endothelin ET(B) receptor in the renal hemodynamic and
      excretory responses to big endothelin-1, using A-192621, a selective endothelin
      ET(B) receptor antagonist and the spotting-lethal (sl) rat, which carries a
      naturally occurring deletion in the endothelin ET(B) receptor gene. An
      intravenous injection of big endothelin-1 produced a hypertensive effect, which
      is greater in wild-type (+/+) rats pretreated with A-192621 and in homozygous
      (sl/sl) rats. Big endothelin-1 markedly increased urine flow, urinary excretion
      of sodium and fractional excretion of sodium in wild-type rats treated with the
      vehicle. These excretory responses to big endothelin-1 were markedly reduced by
      pharmacological endothelin ET(B) receptor blockade. On the other hand, big
      endothelin-1 injection to the endothelin ET(B) receptor-deficient homozygous
      animals resulted in a small diuretic effect. When renal perfusion pressure was
      protected from big endothelin-1-induced hypertension by an aortic clamp, the
      excretory responses in vehicle-treated wild-type rats were markedly attenuated.
      In homozygous or A-192621-treated wild-type rats, there was a small but
      significant decreasing effect in urine flow. In addition, big endothelin-1
      significantly elevated nitric oxide (NO) metabolite production in the kidney of
      wild-type rats but not in the homozygous rats. We suggest that the diuretic and
      natriuretic responses to big endothelin-1 consist of pressure-dependent and
      pressure-independent effects and that the increased NO production via the
      activation of endothelin ET(B) receptors in the kidney is closely related to the
      big endothelin-1-induced excretory responses.

PMID- 12231390
TI  - Active bicarbonate-dependent secretion evoked by 5-hydroxytryptamine in porcine
      ileal mucosa is mediated by opioid-sensitive enteric neurons.
AB  - 5-Hydroxytryptamine (5-HT) mediates intestinal hypersecretion associated with
      infection and inflammation. We tested the hypothesis that 5-HT-induced anion
      secretion is mediated by an opioid-sensitive enteric neural circuit. 5-HT, at a
      contraluminal concentration of 10 microM, increased short-circuit current by 58
      +/- 7 microA/cm(2) in sheets of porcine ileal mucosa with attached inner
      submucosal plexus. Responses to 5-HT were inhibited by saxitoxin or indomethacin,
      and reduced in tissues bathed in Cl(-)- or HCO(3)(-)-deficient media. 5-HT action
      was attenuated by saxitoxin in tissues bathed in Cl(-)-free media, but not HCO(3)
      free media. The delta-opioid receptor agonist [D-Pen(2,5)]enkephalin (0.1 microM)
      blunted the 5-HT change in short-circuit current by a mechanism sensitive to the
      delta-opioid receptor antagonist naltrindole. The inhibitory actions of [D
      Pen(2,5)]enkephalin and saxitoxin were not additive. These results suggest that 5
      HT stimulates HCO(3)(-)-dependent ion transport through a mechanism involving
      prostanoids and an enteric neural pathway modulated by opioids.

PMID- 12231391
TI  - Effect of Helicobacter pylori on delay in ulcer healing induced by aspirin in
      rats.
AB  - Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are major
      pathogenic factors in peptic ulcer disease but whether these two factors exert
      synergistic or antagonistic effects on ulcer healing has been a subject of
      controversy. We compared the effect of aspirin alone with that of aspirin
      combined with H. pylori on gastric acid secretion and healing of acetic acid
      gastric ulcers in rats. The H. pylori colonization of gastric mucosa was
      determined by viable H. pylori culture, histology and assessment of bacterial DNA
      using polymerase chain reaction (PCR). The area of ulcers, gastric blood flow,
      mucosal generation of prostaglandin E(2) and plasma gastrin levels and expression
      of cyclooxygenase-1, cyclooxygenase-2 and growth factors was determined. Aspirin
      delayed significantly the healing of chronic gastric ulcers, decreased the
      gastric blood flow at the ulcer margin and gastric mucosal prostaglandin E(2)
      generation being without significant influence on gastric acid output. H. pylori
      acquisition that produced moderate gastric inflammation at the ulcer margin
      delayed significantly the healing of gastric ulcers, decreased significantly both
      the gastric blood flow at the ulcer margin and the gastric secretion while
      raising significantly the gastric mucosal prostaglandin E(2) generation and
      plasma gastrin levels. H. pylori infection attenuated the aspirin-induced
      inhibition of ulcer healing and accompanying fall in the gastric blood flow. Both
      aspirin and H. pylori up-regulated significantly cyclooxygenase-2 messenger RNA
      (mRNA) and protein but not that of cyclooxygenase-1 at the ulcer margin. Aspirin
      reduced significantly the transforming growth factor alpha- and vascular
      endothelial growth factor mRNAs, but these effects were significantly attenuated
      by H. pylori. We conclude that H. pylori antagonizes, in part, aspirin-induced
      delay of ulcer healing due to suppression of acid secretion, the enhancement in
      prostaglandin E(2) possibly derived from cyclooxygenase-2 and the overexpression
      of transforming growth factor alpha and vascular endothelial growth factor in the
      ulcer area.

PMID- 12231392
TI  - Protection by a radical scavenger edaravone against cisplatin-induced
      nephrotoxicity in rats.
AB  - Acute renal failure is a dose-limiting factor of cisplatin chemotherapy. Here, we
      show the protective effect of edaravone, a recently developed radical scavenger
      for clinical use, against cisplatin-induced renal dysfunction in rats. A marked
      increase in blood urea nitrogen and creatinine in serum, and histological changes
      including vacuolation, necrosis and protein casts were observed in proximal renal
      tubules at the fourth day after cisplatin injection (5-10 mg/kg). Repeated
      injection of edaravone (1-10 mg/kg, i.v. twice a day for 3 days) reversed the
      cisplatin-induced elevation of blood urea nitrogen and creatinine, and
      morphological changes in a dose-dependent manner. In particular, the protective
      effect of edaravone was almost complete at 10 mg/kg. Moreover, the compound was
      still fully effective, when it was administered only at the second day after
      cisplatin injection. On the other hand, the glutathione content in renal tissues
      lowered at the fourth day after cisplatin injection, which was reversed by the
      late treatment with edaravone. These findings suggest that the clinically
      available radical scavenger edaravone is potentially useful for the prevention of
      cisplatin-induced renal toxicity.

PMID- 12231393
TI  - Baclofen influences lipopolysaccharide-mediated interleukin-6 release from murine
      pituicytes.
AB  - Pituicytes, the glial cells of the neurohypophysis, secrete interleukin-6 upon
      stimulation with various inflammatory mediators, i.e. lipopolysaccharide.
      Previous studies have identified several receptors on pituicytes. This study
      investigates the effect of GABA(B) receptor activation on interleukin-6 release
      from pituicytes. Cultured murine pituicytes were stimulated for 24 h with
      lipopolysaccharide (0.5 ng/ml) to give a significant interleukin-6 release
      compared to control. The interleukin-6 release was significantly potentiated by
      the GABA(B) receptor agonist (R)-4-amino-3-(4-chlorophenyl) butanoic acid (R
      baclofen; 10, 100 or 500 microM). However, R-baclofen itself (10, 100 or 500
      microM) did not stimulate the interleukin-6 secretion. Furthermore, the potent
      GABA(B) receptor antagonists 3-[[(3,4
      Dichlorophenyl)methyl]amino]propyl]diethoxymethyl) phosphinic acid (CGP52432; 30
      or 300 microM) and (RS)-3-Amino-2-(4-chlorophenyl)-2-hydroxypropyl-sulphonic acid
      (2-OH-saclofen; 10 or 100 microM) did not remove the effect of R-baclofen (100
      microM). Gamma-amino butyric acid (GABA; 30 or 300 microM) did not alter the
      lipopolysaccharide-mediated interleukin-6 response. After 30 min, intracellular
      cyclic AMP (cAMP) was higher in cells stimulated with lipopolysaccharide compared
      to control, and R-baclofen significantly inhibited this increase in cAMP.
      Nevertheless, neither lipopolysaccharide nor R-baclofen had any effect on
      intracellular cAMP after 24 h of stimulation. The results suggest that the effect
      of R-baclofen on lipopolysaccharide-stimulated interleukin-6 secretion is
      independent of GABA(B) receptors.

PMID- 12231394
TI  - NN2211: a long-acting glucagon-like peptide-1 derivative with anti-diabetic
      effects in glucose-intolerant pigs.
AB  - Glucagon-like peptide-1 (GLP-1) is an effective anti-diabetic agent, but its
      metabolic instability makes it therapeutically unsuitable. This study
      investigated the pharmacodynamics of a long-acting GLP-1 derivative (NN2211:
      (Arg(34)Lys(26)-(N- epsilon -(gamma-Glu(N-alpha-hexadecanoyl)))-GLP-1(7-37)),
      after acute and chronic treatment in hyperglycaemic minipigs. During
      hyperglycaemic glucose clamps, NN2211 (2 micrograms kg(-1) i.v.) treated pigs
      required more (P < 0.005) glucose than control animals (5.8 +/- 2.1 vs. 2.9 +/-
      1.8 mg kg(-1) min(-1)). Insulin excursions were higher (P < 0.01) after NN2211
      (15,367 +/- 5,438 vs. 9,014 +/- 2,952 pmol l(-1) min), and glucagon levels were
      suppressed (P < 0.05). Once-daily injections of NN2211 (3.3 micrograms kg(-1)
      s.c.) reduced the glucose excursion during an oral glucose tolerance test, to 59
      +/- 15% of pre-treatment values by 4 weeks (P < 0.05), without measurable changes
      in insulin responses. Fructosamine concentrations were unaltered by vehicle, but
      decreased (from 366 +/- 187 to 302 +/- 114 micromol l(-1), P = 0.14) after 4
      weeks of NN2211. Gastric emptying was reduced (P < 0.05) by NN2211. NN2211
      acutely increases glucose utilization during a hyperglycaemic glucose clamp and
      chronic treatment results in better daily metabolic control. Therefore, NN2211, a
      GLP-1 derivative that can be administered once daily, holds promise as a new anti
      diabetic drug with a minimal risk of hypoglycaemia.

PMID- 12231395
TI  - Regulation of mdm2 mRNA expression in human breast tumor-derived GI-101A cells.
AB  - The MDM2 oncoprotein (p90) binds to p53 and inhibits its function. Here, the
      expression of mdm2 mRNA subsequent to phorbol 12,13-dibutyrate (PDB) or
      diethylstilbestrol (DES) treatment was analyzed in human breast tumor-derived GI
      101A cell line. Expression of mdm2 mRNA was detected in rapidly growing GI-101A
      cells and that was similar to the expression seen in HL-60 cells. On the other
      hand PC12 (rat adrenal pheochromocytoma cells) did not show any mdm2 expression.
      GI-101A cells were treated with varying concentrations of DES or PDB, and mdm2
      mRNA levels were determined by RT-PCR analysis. The RT-PCR results clearly showed
      that mdm2 mRNA expression was increased with increasing concentrations of PDB and
      DES treatments. To determine the specificity of the effects produced by DES and
      PDB the cells were treated with estrogen receptor antagonist tamoxifen and
      protein kinase C (PKC) specific inhibitor chelerythrine. Tamoxifen and
      chelerythrine co-treatments inhibited DES and PDB stimulated increases of mdm2
      transcription respectively, in GI-101A cells. In an attempt to determine the
      upstream signaling pathway, the effects of PDB or DES on the mitogen activated
      protein kinase (MAPK) levels were determined by western blot analysis in the
      presence and absence of PD098059, a specific inhibitor of mitogen activated
      protein kinase kinase (MAPKK). The phospho-MAPK (p44/42) levels, an activated
      form of MAPK, increased in DES and PDB stimulated cells whereas PD098059
      treatment inhibited this increase. Our data implicate MAPK as an upstream
      regulator of mdm2 expression and help to speculate on the intracellular
      regulation of mdm2 expression.

PMID- 12231396
TI  - Urinary excretion patterns of 5-hydroxyindole-3-acetic acid and 5
      hydroxytryptophol in various animal species: implications for studies on
      serotonin metabolism and turnover rate.
AB  - The concentrations of the serotonin metabolites 5-hydroxyindole-3-acetic acid
      (5HIAA) and 5-hydroxytryptophol (5HTOL) were determined in spot urine samples of
      12 mammalian and one fish species (cat, cow, dog, ferret, golden hamster, guinea
      pig, horse, monkey, mouse, rabbit, rainbow trout, rat, sheep) and compared with
      human data. The highest urinary concentrations of 5HTOL were found in the Sprague
      Dawley rat (mean 9.5 micromol/L) and NMRI mouse (8.2 micromol/L), and the lowest
      in rainbow trout, cynomolgus macaque, and human urine (approximately 0.1
      micromol/L). The highest 5HIAA concentrations were found in hamster (89.3
      micromol/L) and mouse (85.2 micromol/L), and the lowest in rainbow trout, horse
      and sheep (range 2.0-3.7 micromol/L). Several species showed 5HIAA concentrations
      similar to that normally observed in human urine (approximately 5-40 micromol/L).
      This study demonstrated wide inter- and intra-species variations in the urinary
      concentrations of 5HIAA and 5HTOL, both separately and in the sum of
      concentrations. The 5HTOL/5HIAA ratio, which is used as an easily accessible
      index of the relative importance of the reductive and oxidative pathways for
      serotonin metabolism, also varied considerably between different species. This
      observation confirms that the much higher urinary 5HTOL/5HIAA ratio in rats (mean
      0.35) compared with humans (< 0.01) is due to a higher baseline formation of
      5HTOL in the rat. The monkey, ferret, hamster, and rabbit most closely resembled
      humans in this respect, and at least the two latter species appear to be more
      suitable than rats as animal models for studying serotonin metabolism and
      turnover rate, and the metabolic interaction with ethanol.

PMID- 12231397
TI  - Diabetes is not a potent inducer of neuronal cell death in mouse sensory ganglia,
      but it enhances neurite regeneration in vitro.
AB  - We examined the effects of diabetes on the morphological features and
      regenerative capabilities of adult mouse nodose ganglia (NG) and dorsal root
      ganglia (DRG). By light and electron microscopy, no apoptotic cell death was
      detected in the ganglia obtained from either streptozotocin (STZ)-induced
      diabetic or normal C57BL/6J mice in vivo. Neurite regeneration from transected
      nerve terminals of NG and DRG explants in culture at normal (10 mM) and high (30
      mM) glucose concentrations was significantly enhanced in the diabetic mice.
      Chromatolytic changes (i.e. swelling and migration of the nucleus to an eccentric
      position in the neurons, and a loss of Nissl substance in the neuronal perikarya)
      and apoptotic cell death (less than one-fifth of the neurons) in the cultured
      ganglia were present, but neither hyperglycemia in vivo nor high glucose
      conditions in vitro altered the morphological features of the ganglia or the
      ratios of apoptotic cells at 3 days in culture. By semiquantitative RT-PCR
      analysis, the mRNA expressions of ciliary neurotrophic factor (CNTF) in DRG from
      both mice were down-regulated at 1 day in culture. The expression in diabetic
      DRG, but not in control DRG, was significantly up-regulated at later stages (3
      and 7 days) in culture. In summary, hyperglycemia is unlikely to induce cell
      death in the sensory ganglia, but enhances the regenerative capability of vagal
      and spinal sensory nerves in vitro. The up-regulation of CNTF mRNA expression
      during the culture of diabetic DRG may play a role in the enhanced neurite
      regeneration.

PMID- 12231399
TI  - Prolactin and growth hormone response to intracerebroventricular administration
      of the food opioid peptide gluten exorphin B5 in rats.
AB  - Although it has long been known that opioid peptides cause marked changes of
      pituitary hormone secretion in both animals and humans, little is known about the
      possible effect(s) of food-derived opioids (exorphins) on pituitary function. In
      order to investigate the possible role of exorphins derived from wheat gluten on
      pituitary function, we gave the following treatments to four groups of male rats:
      intracerebroventricular (ICV) vehicle, Gluten Exorphin B5 (GE-B5) 200 microg ICV,
      naloxone intraperitoneally (IP) followed by vehicle ICV, naloxone IP followed by
      GE-B5 ICV. Blood samples for Prolactin (PRL) and Growth Hormone (GH) were taken
      at intervals for 90 minutes after vehicle or GE-B5 administration. GE-B5 strongly
      stimulated PRL secretion; its effect was completely abolished by naloxone
      administration. GH secretion was unaffected by GE-B5 under these experimental
      conditions. The present study shows for the first time that an opioid peptide
      derived from wheat gluten, GE-B5, has an effect on pituitary function when
      administered ICV; its mechanism of action appears to be mediated via classical
      opioid receptors.

PMID- 12231398
TI  - Selective changes in DNA binding activity of transcription factors in UM-X7.1
      cardiomyopathic hamsters.
AB  - UM-X7.1 hamsters (CH) are considered a representative model for human
      cardiomyopathy. CH display the loss of the cytoskeletal delta-sarcoglycan
      protein, associated with myocardium remodeling and fatal reduction of heart
      functional efficiency. Even though altered redox balance and calcium homeostasis
      have already been reported to affect cardiomyocyte function, the molecular
      mechanisms underlying this pathology are largely unknown. We found no significant
      differences in DNA binding activity of redox-related (NF-kappaB, Sp1, AP-1 and AP
      2) transcription factors in heart ventricles of 90 day-old CH, compared to normal
      animals. On the other hand, DNA binding activity of calcium-dependent
      transcription factors NF-AT3 and CREB were increased and decreased respectively
      in CH vs. normal ventricles. Western blot experiments confirmed the down
      regulation of CREB levels and suggest a novel regulation mechanism for this
      transcription factor in the heart. Our results are consistent with recent studies
      on NF-AT3, GATA4 and CREB transgenic mice, and provide clues for the
      comprehension of pathogenetic mechanisms of hamster hereditary cardiomyopathy.

PMID- 12231400
TI  - Palgin sensitizes the adriamycin-induced apoptosis via the enhancement of Fas/Fas
      ligand expression.
AB  - This study was designed to evaluate the synergistic cytotoxicity of herb
      prescription, Palgin, in adriamycin-treated cancer cells. The combination of
      Palgin and adriamycin synergistically augmented the cytotoxicity of Chang and HL
      60 cells, but not in Hep3B and Alexander cells. The cytotoxicity of two drugs was
      revealed as apoptosis characterized by nuclear fragmentation. The apoptotic cell
      death was accompanied by the activation of caspase-3 as well as cleavage of
      poly(ADP) ribose polymerase (PARP) in Chang cells. Interestingly, a synergistic
      increase in apoptosis by the combination of two drugs was accompanied by the
      enhancement of Fas and Fas ligand (FasL) expression in Chang cells. Taken
      together, the combination of Palgin and adriamycin significantly augmented the
      apoptotic cytotoxicity of Fas-positive cells, such as Chang and HL-60 cells, via
      activation of caspase signaling pathway. This notion will provide a new trial to
      treat cancer patients in clinical fields as a complementary treatment of Western
      and Oriental medicine.

PMID- 12231401
TI  - HMG-CoA reductase inhibitor decreases small dense low-density lipoprotein and
      remnant-like particle cholesterol in patients with type-2 diabetes.
AB  - Patients with type 2 diabetes are known to have abnormalities in their remnant
      metabolism and low density lipoprotein (LDL) subfraction pattern, with a
      preponderance of small dense LDL. The effects of pitavastatin, a newly
      synthesized 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor,
      on lipoprotein profiles in patients with type 2 diabetes were determined. Thirty
      three patients were treated with pitavastatin with a daily dose of 2 mg for 8
      weeks. After treatment, triglyceride, total and LDL cholesterol were
      significantly reduced by 28.7 +/- 36.7%, 25.2 +/- 14.3% and 36.1 +/- 14.3%,
      respectively. Remnant-like particle cholesterol (RLP-C), an independent risk
      factor for CAD which is known to be elevated in diabetic patients, was also
      significantly reduced (-30.9 +/- 30.5%) by the treatment and this decrease
      correlated well with the decrease in triglyceride level. The proportion of small
      dense LDL, which is known for its atherogenisity, decreased from 29.9 +/- 26.2%
      to 19.7 +/- 22.7% and the mean LDL particle size significantly increased from
      26.36 +/- 1.13 nm to 27.10 +/- 1.36 nm. Pitavastatin, which is known to improve
      triglyceride levels and cholesterol levels, also improves RLP-C level and LDL
      subfraction profiles, and this in turn may reduce the cardiovascular risk in
      patients with type 2 diabetes and dyslipidemia.

PMID- 12231402
TI  - Organic osmolytes betaine, sorbitol and inositol are potent inhibitors of
      erythrocyte membrane ATPases.
AB  - Organic osmolytes are used in animal and plant cells to adapt to hyper- and
      hypoosmolar stress. We used our RBC-membrane model to investigate the effects of
      the osmolytes betaine, sorbitol and myo-inositol on Na(+)/K(+)-ATPase, Ca(2+)
      ATPase and calmodulin-stimulated Ca(2+)-ATPase (CaM). Our results show that
      betaine inhibited ATPases by more than 61%: Na(+)/K(+)-ATPase (75 +/- 5.9 vs 27
      +/- 2.2), Ca(2+)-ATPase (236 +/- 18.9 vs 62 +/- 4.9), and CaM (450 +/- 18 vs 174
      +/- 6.9) (microM pi/min/mg protein, control (0 microM betaine) vs 100 micromol/L
      betaine). Sorbitol (100 micromol/L) inhibited the Ca(2+)-ATPases by 41% (126 +/-
      7.6 vs 74 +/- 4.4) and CaM by 42% (253 +/- 17.7 vs 147 +/- 10.3). Inositol (100
      micromol/L) inhibited Na(+)/K(+)-ATPase strongest (37 +/- 1.9 vs 20 +/- 1.0; 47%
      inhibition) while it showed a lesser effect on the Ca(2+)-ATPases (136 +/- 6.8 vs
      102 +/- 5.1; 25% inhibition). All osmolytes inhibited RBC membrane ATPases at
      concentrations above 50 micromol/L, which corresponds to high normal physiologic
      range for organic osmolytes in serum. Furthermore, the presence of osmolytes (250
      micromol/L) decreased hypoosmotic stress induced hemolysis by 42%. Together these
      data indicate an important regulatory role of organic osmolytes on human RBC
      membrane ATPases and a protective function of osmolytes in RBCs against
      hypoosmotic stress.

PMID- 12231403
TI  - Enhancement of MT synthesis by leptin in fasted mice.
AB  - It is known that metallothionein (MT) synthesis occurs in the liver in various
      stressful situations such as immobilization and fasting. However, the mechanism
      of MT synthesis in stressful situations is not fully understood. In this study,
      we examined the involvement of leptin, the obese gene product, in MT synthesis
      induced by fasting stress. Despite an increase in hepatic MT levels induced by 24
      hr fasting in wild-type mice, both wild-type and MT-null mice showed decreases in
      plasma leptin levels after 24 hr of fasting. Hepatic MT levels increased to
      levels comparable with that in control mice in ICR, C3H, 129Sv and Balb/c mice
      fasted for 24 hr, and plasma leptin levels decreased significantly. Repetition of
      fasting and feeding in turn every 24 hr caused a gradual decrease in hepatic MT
      levels after the fasting period. In contrast, the reduced plasma leptin levels
      increased after the fasting period with repetition of fasting-feeding cycles. The
      findings indicate that there is an adaptation to starvation. On the other hand,
      subcutaneous leptin infusion in fasted mice via an osmotic pump resulted in
      increases in hepatic MT levels compared to the levels in vehicle-treated mice
      after 24 hr of fasting. Only leptin infusion had no effect on hepatic MT levels.
      These results suggest that MT synthesis in fasting stress is not correlated with
      decrease in plasma leptin levels but that leptin itself is a potent inducer of MT
      in a fasting situation.

PMID- 12231404
TI  - Protease-activated receptor-2 (PAR-2) in the pancreas and parotid gland:
      Immunolocalization and involvement of nitric oxide in the evoked amylase
      secretion.
AB  - Protease-activated receptor-2, a G protein-coupled receptor activated by serine
      proteases such as trypsin, tryptase and coagulation factors VIIa and Xa,
      modulates pancreatic and salivary exocrine secretion. In the present study, we
      examined the distribution of PAR-2 in the pancreas and parotid gland, and
      characterized the PAR-2-mediated secretion of amylase by these tissues in vivo.
      Immunohistochemical analyses using the polyclonal antibody against rat PAR-2
      clearly showed abundant expression of PAR-2 in rat pancreatic and parotid acini.
      The PAR-2 agonist SLIGRL-NH2, administered intraperitoneally (i.p.) at 1-10
      micromol/kg and 1.5-15 micromol/kg, in combination with amastatin, an
      aminopeptidase inhibitor, facilitated in vivo secretion of pancreatic and
      salivary amylase in a dose-dependent manner, respectively, in the mouse. The PAR
      2-mediated secretion of pancreatic amylase was abolished by pretreatment with
      N(G)-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor. The
      secretion of salivary amylase in response to the PAR-2 agonist at a large dose,
      15 micromol/kg, but not at a smaller dose, 5 micromol/kg, was partially reduced
      by L-NAME. Pretreatment with capsaicin for ablation of the sensory neurons did
      not modify the PAR-2-mediated secretion of pancreatic and salivary amylase in the
      mouse. In conclusion, our study demonstrates expression of PAR-2 in rat
      pancreatic acini as well as parotid acini and indicates that nitric oxide
      participates in the PAR-2-mediated in vivo secretion of pancreatic amylase, and,
      to a certain extent, of salivary amylase, although capsaicin-sensitive sensory
      neurons, known to be activated by PAR-2, are not involved in the evoked
      pancreatic or salivary amylase secretion.

PMID- 12231405
TI  - Identification of 8-iso-prostaglandin F(2alpha) in rat brain neuronal endings: a
      possible marker of membrane phospholipid peroxidation.
AB  - Isoprostanes are a family of prostaglandin (PG) F and E isomers generated by free
      radical attack from membrane bound arachidonic acid. We measured detectable
      levels of 8-iso-PGF(2alpha) in the perfusates of synaptosomes obtained from
      different areas of the rat brain cortex. A small but significant release of this
      isoprostane was found under basal conditions from all the areas explored; being
      lower in the dorsal cortex in respect to the frontal, parietal and occipital
      areas. Exposure of synaptosomes to a phospholipase A(2) activator, i.e. calcium
      ionophore A23187, an oxidant agent, such as hydrogen peroxide or amyloid beta
      peptide did not modify 8-iso-PGF(2alpha) release when these stimuli were applied
      separately. However, either hydrogen peroxide or amyloid beta-peptide increased 8
      iso-PGF(2alpha) release in a dose-dependent manner, when given in the presence of
      the calcium-ionophore A23187. Synaptosome treatment with a non-selective
      cyclooxygenase inhibitor (fenoprofen) did not modify 8-iso-PGF(2alpha) release in
      any way, but treatment with a water soluble antioxidant (Trolox C) completely
      suppressed isoprostane release under basal conditions, as well as after the
      oxidant injury induced either by hydrogen peroxide or amyloid beta-peptide. We
      conclude that, in neuronal endings, 8-iso-PGF(2alpha) is generated under basal
      conditions and its formation may be increased in a dose-dependent fashion by
      oxidant stimuli through a cyclooxygenase-independent mechanism involving free
      radical-catalyzed oxidation of arachidonic acid on membrane phospholipids.

PMID- 12231406
TI  - Contribution of trabecular and cortical components to the mechanical properties
      of bone and their regulating parameters.
AB  - To evaluate the mechanical contributions of the spongiosa and cortex to the whole
      rat vertebra, we developed a finite element analysis (FEA) system linked to three
      dimensional data from microcomputed tomography (micro-CT). Twenty-eight fifth
      lumbar vertebrae (L-5) were obtained from 10-month-old female rats, comprised of
      ovariectomized (ovx, n = 6), sham operated (n = 7), and alfacalcidol-treated
      after ovx (0.1 microg/kg [n = 8] and 0.2 microg/kg [n = 7]) groups. The
      trabecular microstructure of L-5 was measured by micro-CT. Yield strength at the
      tissue level (YS), defined as the value at which 0.034% of all elements reached
      yield stress, was calculated by the FEA. Then, the ultimate compressive load of
      each specimen was measured by mechanical testing. The YS of the whole bone (YSw)
      showed a significant correlation with ultimate load (r = 0.91, p < 0.0001). The
      YS values of the isolated spongiosa (YSs) and cortex (YSc) were calculated in
      models with varying amounts of trabecular or cortical bone mass. The mechanical
      contribution of the spongiosa showed a nonlinear relationship with bone mass, and
      ovx reduced the mean mechanical contribution of the spongiosa to the whole bone
      by 13% in comparison to the sham group. YSs had a strong relationship with
      trabecular microstructure, especially with trabecular bone pattern factor (TBPf)
      and structure model index (SMI), and YSc had a strong relationship with cortical
      bone volume. The structural parameters most strongly related to YSw were BV/TV
      and TBPf. Our micro-FEA system was validated to assess the mechanical properties
      of bone, including the individual properties of the spongiosa and cortex, in the
      osteoporotic rat model. We found that the mechanical property of each component
      had a significant relationship with the respective bone mass, volume, or
      structure. Although trabecular microstructure has a significant relationship with
      bone strength, in ovx bone with deteriorated trabecular microstructure, the
      strength depended mainly on the cortical component.

PMID- 12231407
TI  - Calcitonin induces dephosphorylation of Pyk2 and phosphorylation of focal
      adhesion kinase in osteoclasts.
AB  - Calcitonin induces the association and tyrosine phosphorylation of focal adhesion
      kinase (FAK), paxillin, and HEF1 in HEK-293 cells that overexpress the calcitonin
      receptor (C1a-HEK), but the hormone's effect on these adhesion-related proteins
      in osteoclasts is not known. We therefore studied the effect of calcitonin on the
      tyrosine phosphorylation and subcellular distribution of paxillin, HEF1, FAK, and
      Pyk2, a FAK-related tyrosine kinase, in osteoclasts. Osteoclasts expressed both
      Pyk2 and FAK, with Pyk2 much more highly expressed. The two tyrosine kinases and
      paxillin were prominently associated with small punctate structures that were
      most densely clustered in the region of the peripheral F-actin-rich ring. Some of
      the punctate structures stained either for Pyk2 alone or FAK alone. Treatment
      with calcitonin disrupted the actin ring and induced the loss of the peripheral
      staining of paxillin, Pyk2, and FAK. In calcitonin-treated osteoclast-like cells,
      the tyrosine phosphorylation of paxillin and FAK increased, whereas the tyrosine
      phosphorylation of Pyk2 decreased. Calcitonin also induced increased
      phosphorylation of Erk1 and Erk2 in osteoclasts, as it did in the C1a-HEK cells.
      The unexpected dephosphorylation of Pyk2 correlated with decreased
      phosphorylation of Tyr(402), the autophosphorylation site of Pyk2. The calcitonin
      induced dephosphorylation of Pyk2 was not observed in C1a-HEK cells transfected
      with Pyk2, suggesting that the reduced phosphorylation seen in osteoclasts may be
      specific to these cells. Treatment of osteoclast-like cells with 12-phorbol 13
      myristate acetate increased the tyrosine phosphorylation of both Pyk2 and FAK,
      and calphostin C, an inhibitor of protein kinase C, blocked calcitonin-stimulated
      FAK phosphorylation. Increasing intracellular calcium with ionomycin caused a
      decrease in the tyrosine phosphorylation of Pyk2 and the loss of the actin ring
      in a manner similar to the effect of calcitonin. Ionomycin had no effect on FAK
      tyrosine phosphorylation. Calcitonin (CT)-induced changes in Pyk2, FAK, and
      Erk1/2 phosphorylation were independent of c-Src.

PMID- 12231408
TI  - Guidelines on the management of Paget's disease of bone.

PMID- 12231409
TI  - Na+ dependence of extracellular Ca2+-sensing mechanisms leading to activation of
      an outwardly rectifying Cl- channel in murine osteoclasts.
AB  - An elevation in the extracellular Ca(2+) concentration ([Ca(2+)](o)) is a key
      signal for bone remodeling by inhibiting the resorbing activity of osteoclasts.
      The [Ca(2+)](o)-sensing responses include a variety of morphological and
      functional changes, but the underlying mechanisms are yet to be defined. This
      study was aimed at investigating the [Ca(2+)](o)-sensing mechanisms leading to
      the activation of the Cl(-) channel in murine osteoclasts. A rise in either
      Ca(2+) or Gd(3+) activated an outwardly rectifying Cl(-) (OR(cl)) channel
      reversibly and dose-dependently, which was characterized by rapid activation
      kinetics, little inactivation, and blockage by DIDS. The concentration required
      for a half-maximal response was estimated to be >20-30 mmol/L for Ca(2+).
      Intracellular dialysis with an ATP-free pipette solution or application of an
      actin destabilizer, cytochalasin D, decreased the [Ca(2+)](o)-activated OR(cl)
      current. Substitution of extracellular Na(+) by an impermeable cation, N-methyl-D
      glucamine(+), inhibited the [Ca(2+)](o)-activated OR(cl) channel, suggesting that
      the activation depended on extracellular Na(+). A blocker for the Na(+)-Ca(2+)
      exchanger, 2'4'-dichlorobenzamil hydrochloride (DCB), inhibited the [Ca(2+)](o)
      activated OR(cl) channel as well. Although 10 mmol/L Ca(2+) activated the OR(cl)
      current only slightly at a standard intracellular pH (7.3), decreasing pH by
      dialyzing cells with an acidic pipette solution (pH 6.6) enhanced the [Ca(2+)](o)
      activated OR(cl) current. This potentiation by cell acidosis was eliminated by
      amiloride, a blocker for the Na(+)-H(+) exchanger. Zinc ion (0.1 mmol/L) and a
      polycation, neomycin (0.2 mmol/L), activated the OR(cl) current at intracellular
      pH 6.6, whereas the effects of those cations were negligible at intracellular pH
      7.3. These results suggest that [Ca(2+)](o)-sensing mechanisms, leading to
      activation of the OR(cl) channel in murine osteoclasts, are regulated by ATP and
      actin cytoskeletal organization, and are sensitized greatly by cell acidosis.
      Contributions of Na(+)-dependent transporters in this activating process are
      examined in the context of a possible intermediate signal of cell swelling caused
      by Na(+) influx.

PMID- 12231410
TI  - Vector-averaged gravity-induced changes in cell signaling and vitamin D receptor
      activity in MG-63 cells are reversed by a 1,25-(OH)2D3 analog, EB1089.
AB  - Skeletal unloading in an animal hindlimb suspension model and microgravity
      experienced by astronauts or as a result of prolonged bed rest causes site
      specific losses in bone mineral density of 1%-2% per month. This is accompanied
      by reductions in circulating levels of 1,25-(OH)(2)D(3), the active metabolite of
      vitamin D. 1,25-(OH)(2)D(3), the ligand for the vitamin D receptor (VDR), is
      important for calcium absorption and plays a role in differentiation of
      osteoblasts and osteoclasts. To examine the responses of cells to activators of
      the VDR in a simulated microgravity environment, we used slow-turning lateral
      vessels (STLVs) in a rotating cell culture system. We found that, similar to
      cells grown in microgravity, MG-63 cells grown in the STLVs produce less
      osteocalcin, alkaline phosphatase, and collagen Ialpha1 mRNA and are less
      responsive to 1,25-(OH)(2)D(3). In addition, expression of VDR was reduced.
      Moreover, growth in the STLV caused activation of the stress-activated protein
      kinase pathway (SAPK), a kinase that inhibits VDR activity. In contrast, the 1,25
      (OH)(2)D(3) analog, EB1089, was able to compensate for some of the STLV
      associated responses by reducing SAPK activity, elevating VDR levels, and
      increasing expression of osteocalcin and alkaline phosphatase. These studies
      suggest that, not only does simulated microgravity reduce differentiation of MG
      63 cells, but the activity of the VDR, an important regulator of bone metabolism,
      is reduced. Use of potent, less calcemic analogs of 1,25-(OH)(2)D(3) may aid in
      overcoming this defect.

PMID- 12231411
TI  - Effect of deproteination on bone mineral morphology: implications for
      biomaterials and aging.
AB  - Bone mineral morphology is altered by processing and this is rarely considered
      when preparing bone as a bioimplant material. To examine the degree of
      transformation, a commercial, coarsely particulate bone mineral biomaterial
      produced by prolonged deproteination, defatting, dehydration, and heating (donor
      material) was compared with similar particles of human bone (recipient material)
      prepared optimally by low-temperature milling. The two powders were freeze
      substituted and embedded without thawing in Lowicryl K4M before sectioning for
      transmission electron microscopy (TEM) (other aliquots were processed by
      traditional TEM methods). To maximize resolution, electron micrographs were image
      enhanced by digitization and printed as negatives using a Polaroid Sprint Scan
      45. In addition to their morphology, the particles were examined for antigenicity
      (specific by reference to fluorescein isothiocyanate [FITC]-conjugated
      fibronectin, and nonspecific by reference to general FITC-conjugated
      immunoglobulins). Results showed that the optimally prepared human bone fragments
      stained discretely for fibronectin with negligible background autofluorescence.
      In contrast, the bioimplant fragments stained extensively with this and any other
      FITC-conjugated antibody and, unlike fresh bone, it also autofluoresced a uniform
      yellow. This difference was also expressed structurally and, although the
      bioimplant mineral consisted of rhomboidal plates up to 200 nm across and 10 nm
      thick, the optimally prepared bone mineral was composed of numerous clusters of 5
      nm-wide sinuous calcified filaments of variable density and indeterminate length
      (which became straight needles 50 nm long and 5 nm thick following traditional
      chemical TEM fixation/staining). It was concluded that the inorganic phase of
      bone is both morphologically and immunologically transmutable and that, in
      biomaterials, the transformation is apparently so great that a broad indigenous
      antigenicity is unmasked, increasing the likelihood of resorption or rejection.
      This marked change may also provide preliminary insight into a more modest
      natural aging phenomenon with the localized lateral fusion of calcified filaments
      into less flexible, more immunologically reactive fenestrated plates.

PMID- 12231412
TI  - A phosphodiesterase inhibitor, pentoxifylline, enhances the bone morphogenetic
      protein-4 (BMP-4)-dependent differentiation of osteoprogenitor cells.
AB  - Bone morphogenetic protein-4 (BMP-4), a member of the transforming growth factor
      beta superfamily, is capable of initiating differentiation of uncommitted
      mesenchymal cells into a chondro/osteogenic pathway. This study reports the
      effects of pentoxifylline (PTX), a nonspecific inhibitor of phosphodiesterases
      (PDEs), that causes elevation of the intracellular cyclic adenosine monophosphate
      (cAMP) level on the BMP-4-induced chondro/osteogenic differentiation of a
      mesenchymal cell line, C3H10T1/2; a bone marrow stromal cell line, ST2; and an
      osteoblastic cell line, MC3T3-E1. It was found that PTX enhanced BMP-4-induced
      chondro/osteogenic differentiation in C3H10T1/2 and ST2 cells. Similar effects
      were observed when adding dibutyryl-cAMP and forskolin. These results indicate
      that cAMP may potentiate the action of BMP-4 on osteoprogenitor cells,
      highlighting the possibility that PDE inhibitors could be used as therapeutic
      agents to enhance bone formation through this effect.

PMID- 12231413
TI  - Bipedal stance exercise and prostaglandin E2 (PGE2) and its synergistic effect in
      increasing bone mass and in lowering the PGE2 dose required to prevent
      ovariectomized-induced cancellous bone loss in aged rats.
AB  - Previous reports have shown that bone loss was partially prevented by bipedal
      stance "exercise" following ovariectomy (ovx), and it was well documented that
      prostaglandin E2 (PGE(2)) had an anabolic effect on the rat skeleton. The aim of
      this study was to determine whether lower doses of PGE(2) could prevent ovx
      induced cancellous bone loss with the combination of bipedal stance exercise.
      Seventy-eight 10-month-old female Sprague-Dawley rats were either ovariectomized
      or sham-operated on day 0 and then treated with PGE(2) (0, 0.3, or 1 mg/kg per
      day) and/or housed in normal height cages (NC, 28 cm) or raised cages (RC, 33 cm)
      for 8 weeks. Bone histomorphometry was performed on the double-fluorescent
      labeled proximal tibial metaphysis. In sham rats, 1 mg/kg PGE(2) + RC had
      synergistic effects in increasing trabecular bone area, width, and number by
      stimulating mineral apposition rate and bone formation rate. As expected, ovx
      induced cancellous bone loss, accompanied by elevated activation frequency.
      Without RC, PGE(2) monotherapy prevented ovx-induced bone loss at the 1 mg/kg per
      day dose, whereas this prevention effect was observed at the 0.3 mg/kg per day
      dose when combined with RC. Similar to their effects in sham rats, PGE(2) and RC
      had synergistic effects in augmenting cancellous bone mass and architecture and
      maintaining the elevated bone formation but depressing bone resorption and
      activation frequency. We conclude that bipedal stance exercise lowers the PGE(2)
      dose required to prevent ovx-induced cancellous bone loss in the proximal tibial
      metaphysis in aged rats.

PMID- 12231414
TI  - Validation of a technique for studying functional adaptation of the mouse ulna in
      response to mechanical loading.
AB  - Functional adaptation of the mouse ulna in response to artificial loading in vivo
      was assessed using a technique previously developed in the rat. Strain gauge
      recordings from the mouse ulnar midshaft during locomotion showed peak strains of
      1680 muepsilon and maximum strain rates of 0.03 sec(-1). During falls from 20 cm
      these reached 2620 muepsilon and 0.10 sec(-1). Axial loads of 3.0 N and 4.3 N,
      applied through the olecranon and flexed carpus, engendered peak strains at the
      lateral ulnar midshaft of 2000 muepsilon and 3000 muepsilon, respectively. The
      left ulnae of 17, 17-week-old female CD1 mice were loaded for 10 min with a 4 Hz
      trapezoidal wave engendering a strain rate of 0.1 sec(-1) for 5 days/week for 2
      weeks. The mice were killed 3 days later. The response of the cortical bone of
      the diaphysis was assessed histomorphometrically using double calcein labels
      administered on days 3 and 12 of the loading period. Loading to peak strains of
      2000 muepsilon stimulated lamellar periosteal bone formation, but no response
      endosteally. The greatest increase in cortical bone area was 4 mm distal to the
      midshaft (5 +/- 0.4% compared with 0.1 +/- 0.1% in controls [p < 0.01]).
      Periosteal bone formation rate (BFR) at this site was 0.73 +/- 0.06
      microm(2)/microm per day, compared with 0.03 +/- 0.02 microm(2)/microm per day in
      controls (p < 0.01). Loading to peak strains of 3000 muepsilon induced a mixed
      woven/lamellar periosteal response and lamellar endosteal bone formation. Both of
      these were greatest 3-4 mm distal to the ulnar midshaft. At this level, the
      loading-induced periosteal response increased cortical bone area by 21 +/- 4%
      compared with 0.03 +/- 0.02% in controls, and resulted in a BFR of 2.84 +/- 0.42
      microm(2)/microm per day, compared with 0.01 +/- 0.01 microm(2)/microm per day in
      controls (p < 0.05). Endosteal new bone formation resulted in a 2 +/- 0.4%
      increase in cortical bone area, compared with 0.4 +/- 0.3% in controls, and a BFR
      of 1.05 +/- 0.23 microm(2)/microm per day, compared with 0.22 +/- 0.15
      microm(2)/microm per day in controls (p < 0.05). These data show that the axial
      ulna loading technique developed in the rat can be used successfully in the
      mouse. As in the rat, a short daily period of loading results in an osteogenic
      response related to peak strain magnitude. One important advantage in using mice
      over rats involves the potential for assessing the effects of loading in
      transgenics.

PMID- 12231415
TI  - Stochastic simulations of remodeling applied to a two-dimensional trabecular bone
      structure.
AB  - In this investigation the stochastic dynamics of trabecular bone remodeling
      (which is a key concept in a range of remodeling models) is verified. For this
      purpose, two-dimensional binary images of horizontal histological sections of
      lumbar vertebral bone (L-3) were collected from young and old subjects. Then the
      stochastic algorithm of remodeling was applied to the images of young trabecular
      bone. The resulting images of "simulated" old structures and those of "real" old
      structures were analyzed to evaluate the following architectural parameters: bone
      volume/trabecular volume; mean area of marrow cavities; mean trabeculae length;
      marrow space star volume; Euler number density; trabecular thickness; trabecular
      number; trabecular separation; mean two-point distance along the skeleton of
      trabecular structure; probability of disconnection; the ratio of marrow space
      star volume to geometrical volume and dimensionless ratio of mean area of marrow
      cavities; and mean trabecular length squared (form factor). Using the parametric
      t-test, the groups of simulated and real old bone images were compared. It is
      found that the p value of the t-test is never less than 0.20. For eight
      parameters the p value is >0.45. It is concluded that, as long as the horizontal
      sections of lumbar vertebrae are considered (sections perpendicular to the
      direction of the main spine load), the stochastic algorithm of bone remodeling
      will properly reproduce the architectural properties of trabecular bone.

PMID- 12231416
TI  - The absolute bioavailability of clodronate from two different oral doses.
AB  - Clodronate (disodium clodronate tetrahydrate) is a bisphosphonate used in the
      treatment of hypercalcemia and osteolysis due to malignancy. Like all
      bisphosphonates, clodronate has low and variable oral bioavailability. The
      purpose of this study was to examine the absolute bioavailability of clodronate
      from two different oral doses. Thirty-one healthy young volunteers participated
      in this open, randomized, three-period, single-dose, cross-over study. The
      absolute bioavailability was calculated from the area under the serum clodronate
      time curve in 48 h (AUC(0-48 h)) after administration of 800 or 1600 mg (Bonefos
      400 mg capsules) of oral clodronate, or 30 mg (Bonefos 60 mg/mL infusion
      concentrate) of intravenous clodronate. The maximum concentration of clodronate
      in serum (C(max)), the time to maximum concentration (t(max)), the elimination
      half-life (t(1/2)), and the cumulative amount of clodronate excreted into urine
      in 48 h (Ae(0-48 h)) were also determined. The geometric mean of the absolute
      bioavailability of 800 mg of clodronate was 1.9% and that of 1600 mg 2.1%. The
      difference in the absolute bioavailability of these two doses was statistically
      nonsignificant. All treatments were well tolerated, and the AE profiles were
      similar in the different treatment groups. There were no serious adverse events
      during the study.

PMID- 12231417
TI  - Monitoring bone density in hypogonadal men by quantitative phalangeal ultrasound.
AB  - Monitoring bone density (BMD) in hypogonadal and testosterone (T) substituted men
      is a major component of andrological therapy and is performed by methods that are
      cost-intensive and use radiation, such as quantitative computer tomography (QCT).
      Therefore, we assessed the feasibility of a more practical and inexpensive
      approach through application of phalangeal quantitative ultrasound (pQUS; IGEA
      DBM BP Sonic 1200, Sensweiler, Germany) in a cross-sectional study of 521 men,
      aged 18-91 years (224 healthy controls, 156 newly diagnosed hypogonadal, and 141
      T substituted men). The method was compared with QCT of the lumbar spine in the
      first 80 patients. We evaluated longitudinal changes of amplitude-dependent speed
      of-sound (AdSoS) in 54 hypogonadal men from the beginning of T substitution.
      AdSoS decreased with age (p < 0.0001) and with declining total T concentration,
      with a four to fivefold larger reduction in AdSoS for each nanomole-per-liter
      decrement in total T in the hypogonadal range (<12 nmol/L) compared with the
      eugonadal range (p < 0.0001). AdSoS was higher in eugonadal and substituted men
      than in hypogonadal patients (p < 0.0001, by analysis of covariance [ANCOVA]).
      Substituted men <50 years of age showed lower AdSoS than eugonadal men (p =
      0.004) and untreated men with secondary hypogonadism had lower values than men
      with primary hypogonadism (p = 0.005). Therapeutic effects were seen regardless
      of age, diagnosis, or T substitution modality. In the longitudinal approach,
      AdSoS increased from 1986 +/- 93 to 2035 +/- 77 m/sec over 237 +/- 57 days with
      the highest gain in those men with initially the lowest values (p < 0.0001, by
      ANCOVA for repeated measurements). In comparison to QCT, patients with a lumbar
      content of hydroxylapatite of <100 mg/cm(3) were reliably identified by pQUS
      (cutoff level 1965 m/sec, T score -3.5 based on eugonadal subjects; receiver
      operating characteristics: area under the curve [AUC] 0.94, sensitivity 94.1,
      specificity 92%, p < 0.0001), but specific values of lumbar BMD could not be
      predicted by pQUS. pQUS represents a feasible, sensitive, and inexpensive method
      for assessing bone tissue in hypogonadal men over the full age range and also for
      monitoring the effects of T substitution.

PMID- 12231418
TI  - Increasing number and incidence of low-trauma ankle fractures in elderly people:
      Finnish statistics during 1970-2000 and projections for the future.
AB  - To increase knowledge about recent trends in the number and incidence of various
      low-trauma injuries among elderly people, we selected, from the National Hospital
      Discharge Register, all patients > or =60 years of age who were admitted to
      hospitals in Finland (5 million population) for primary treatment of a first low
      trauma ankle fracture during 1970-2000. In each year of the study, the age
      adjusted and age-specific incidence of fracture was expressed as the number of
      patients per 100,000 persons. The predicted numbers and incidence rates of
      fractures until the year 2030 were calculated using a regression model. For the
      study period, the number and incidence of low-trauma ankle fractures in Finnish
      persons > or =60 years of age rose substantially: the total number of fractures
      increased from 369 in 1970 to 1545 in 2000, a 319% increase, and the crude
      incidence increased from 57 to 150, a 163% increase. The age-adjusted incidence
      of these fractures also rose in both women (from 66 in 1970 to 174 in 2000, a
      164% increase) and men (from 38 in 1970 to 114 in 2000, a 200% increase). The
      regression model indicates that, if this trend continues, there will be about
      three times more low-trauma ankle fractures in Finland in the year 2030 than
      there was in 2000. In conclusion, the number of low-trauma ankle fractures in
      elderly Finns is rising rapidly at a rate that cannot be explained simply by
      demographic changes and, therefore, potentially effective preventive measures,
      such as prevention of slippings, trippings, and falls in elderly people, and use
      of ankle supports, should be urgently studied.

PMID- 12231419
TI  - Paget's disease of bone in Lancashire and arsenic pesticide in cotton mill
      wastewater: a speculative hypothesis.
AB  - A 1974 survey of Paget's disease of bone in 31 UK towns identified a cluster of
      six Lancashire former cotton mill towns with the highest prevalence rates of the
      disease and noted a link with the cotton industry. The two highest-prevalence
      towns are situated on estuaries and are jointly the smallest of the six by the
      size of their former cotton industry. The two lowest-prevalence towns of the six
      are highest above sea level and jointly the largest by the size of their former
      cotton industry. This pattern suggests a waterborne agent. A 1993 repeat survey
      of 10 of the 31 towns identified a general decline in prevalence, greatest in the
      three cotton towns included from the six in the earlier survey, further
      suggesting a link to the cotton industry. Cotton mills and bleach/dyeworks
      produced a large volume of wastewater that was commonly discharged into adjacent
      waterways. Wastewater contained process chemicals and imported organisms and
      pesticides carried in cotton bales. The process chemicals and imported organisms
      could be discounted as a probable factor in Paget's disease; however, pesticides
      could not be discounted. Lancashire cotton came predominantly from the American
      cotton belt. From 1917 to 1945, calcium arsenate pesticide was used intensively
      to combat the boll weevil and was imported to Lancashire in cotton bales. The
      calcium arsenate era is consistent with the high-prevalence findings in 1974 and
      the decline in 1993, allowing for time lags. Geochemical arsenate is widespread
      in the environment and may account for geographic variations in Paget's
      prevalence, although data are inadequate for correlation studies. Noncytotoxic
      doses of arsenic affect all the steroid receptors and some signal transduction
      pathways, which may lead to dysfunctional osteoclast signaling and
      differentiation. Human cells are more susceptible than animal cells to arsenic,
      based on studies of nonbone cells. It is speculative that arsenic may be a factor
      in the abnormal variation in prevalence rates in Lancashire. It is not a general
      theory of Paget's disease.

PMID- 12231420
TI  - Isomer-specific effects of conjugated linoleic acid (CLA) on adiposity and lipid
      metabolism.
AB  - Isomers of conjugated linoleic acid (CLA), unsaturated fatty acids found in
      ruminant meats and dairy products, have been shown to reduce adiposity and alter
      lipid metabolism in animal, human, and cell culture studies. In particular,
      dietary CLA decreases body fat and increases lean body mass in certain rodents,
      chickens, and pigs, depending on the isomer, dose, and duration of treatment.
      However, the effects of CLA on human adiposity are conflicting because these
      studies have used different mixtures and levels of CLA isomers and diverse
      subject populations. Potential antiobesity mechanisms of CLA include decreased
      preadipocyte proliferation and differentiation into mature adipocytes, decreased
      fatty acid and triglyceride synthesis, and increased energy expenditure,
      lipolysis, and fatty acid oxidation. This review will address the current
      research on CLA's effects on human and animal adiposity and lipid metabolism as
      well as potential mechanism(s) responsible for CLA's antiobesity properties.

PMID- 12231421
TI  - Inhibition of collagen glycation and crosslinking in vitro by methanolic extracts
      of Finger millet (Eleusine coracana) and Kodo millet (Paspalum scrobiculatum).
AB  - The present investigation was carried out to study the effects of methanolic
      extracts of Finger millet (Eleusine coracana) and Kodo millet (Paspalum
      scrobiculatum) on glycation and crosslinking of collagen. Tail tendons obtained
      from rats weighing 200-225 g were incubated with glucose (50 mM) and 3 mg of
      extracts of the above millets in methanol under physiological conditions of
      temperature and pH for 10 days. Early glycation was estimated by phenol-sulfuric
      acid method and the crosslinking was assessed by pepsin digestion, cyanogen
      bromide peptide map and viscosity measurements. Tendon collagen incubated with
      glucose (50 mM) showed 65% solubility on pepsin treatment; poor resolution of
      bands in the cyanogen bromide peptide map, and intrinsic viscosity of 0.84 dl/g.
      The collagen incubated with Finger millet and Kodo millet extracts inhibited
      glycation; 89% and 92% solubility in pepsin; good resolution of bands in the
      cyanogen bromide peptide map and intrinsic viscosity of 0.46 and 0.58 dl/g
      respectively. The study implicates the potential usefulness of the above millets
      in protection against glycation and crosslinking of collagen.

PMID- 12231422
TI  - Modulatory effect of butyric acid-a product of dietary fiber fermentation in
      experimentally induced diabetic rats.
AB  - The effect of feeding of butyric acid on alleviation of diabetic status was
      studied. Diabetes was induced in rats using streptozotocin. Rats were fed with
      basal diet containing wheat bran (5%) as a source of insoluble dietary fiber and
      guar gum (2.5%) as a source of soluble dietary fiber. The experimental group
      received butyric acid at 250, 500 and 750 mg/kg body weight/day. The diabetic
      animals lost weight in spite of high diet consumption. The levels of water
      intake, urine output, urine sugar, fasting blood sugar increased during diabetic
      condition compared to control and these were reduced by nearly 20% in the fiber
      fed diabetic group. Further supplementation of butyric acid at 500 mg/kg body
      weight/day ameliorated the diabetic status by nearly 40%. Urine sugar level
      during the diabetic state was reduced from 7.2 g/day to 3.6 g/day and fasting
      blood glucose from 270 mg/dl to 180 mg/dl. Butyric acid feeding at 500 mg/kg body
      weight/day was most effective in controlling the diabetic status.

PMID- 12231423
TI  - Identification of factors regulating lipoprotein lipase catalyzed hydrolysis in
      rats with the aid of monoacid-rich lipoprotein preparations(1).
AB  - To identify the substrate specificity and regulatory factors in lipoprotein
      lipase (LPL) catalyzed hydrolysis of triacylglycerol-rich lipoprotein, monoacid
      rich lipoproteins were used to study the kinetic parameters of LPL. Feeding
      growing rats with diets rich in palmitic acid (16:0), oleic acid (18:1) or
      linoleic acid (18:2) for 10 days increased the corresponding acid content in the
      triacylglycerols of the lipoproteins. Force-feeding the monoacid-rich
      triacylglycerols, particularly 16:0 or 18:1, increased the respective fatty acid
      content in both chylomicrons and VLDLs. Major apolipoproteins and lipid
      compositions were essentially similar among all lipoproteins differing in
      monoacid species, except for apo A-IV. The Vmax of LPL for 16:0-rich chylomicrons
      and VLDLs were higher than for 18:1- or 18:2-rich lipoproteins. Order parameter
      (S), an indicator of the surface fluidity of lipoproteins, decreased with the
      chain length and unsaturation of monoacid in similar manner as the Vmax. The Vmax
      of LPL increased linearly (P < 0.05) with an increase in either the palmitic acid
      content of the lipoprotein triacylglycerols or order parameter (S) of the
      lipoproteins. The order parameter (S) and Vmax of LPL were higher in 16:0
      triacylglycerol emulsions with apo B than with 18:1 or 18:2 triacylglycerols. The
      apo A-IV in triacylglycerol emulsions stimulated Vmax of LPLs in the presence of
      apo B and apo C-II. The binding of apo A-IV to 16:0 triacylglycerol emulsions was
      higher than to other triacylglycerol emulsions. These findings suggest that
      lipoprotein catalysis by LPL is modulated by the 16:0 level in the lipoprotein
      triacylglycerol, which affects the surface fluidity and apo A-IV content of
      lipoproteins.

PMID- 12231424
TI  - Total salivary IgA, serum C3c and IgA in obese school children.
AB  - Studies of the immunologic function in adult obese humans and experimental models
      indicate that excess adiposity is associated with impairments in host defense
      mechanisms. The aim of this work was to analyze the secretory and humoral immune
      system in obese children (n = 105, 55 boys, 50 girls ), between 6 and 13 years of
      age. Samples of non-stimulated saliva and whole blood were collected from fasting
      patients. Total salivary IgA (IgAsal), serum C3 complement (C3c) and
      Immunoglobulin A (IgA) were determined by quantitative radial immunodifussion on
      agar gel layers ( Diffu-plate, Biocienti;fica SA ). Results, expressed as mg/dl,
      were compared to laboratory reference values from healthy children of either sex
      in the same range of age that belong to the same socioeconomic class (n = 60).
      Data (Mean +/- 1 SD) of the whole population were: IgAsal: 11.4 +/- 4.8 vs 14.8
      +/- 6.9; C3c: 190.7 +/- 53.1 vs 126.3 +/- 45.5; IgA: 194.5 +/- 101.5 vs 157.2 +/-
      19.9. Data distribution showed higher frecuencies near the zone of the highest
      reference values for serum C3c; when results of IgA and IgAsal were expressed as
      percentage of the mean reference value, 51% and 48.6% of the whole studied
      population presented data lower than 100% and 75% respectively. These results
      show a compromised secretory immune system without incidence of clinical symptoms
      and infections, whereas humoral immunity might not be profoundly affected.

PMID- 12231425
TI  - Vitamin E improves bone quality in the aged but not in young adult male mice.
AB  - It is generally viewed that with advancing age, humans and other animals
      including mice experience a gradual decline in the rate of bone formation. This,
      in part, may be due to the rise in oxygen-derived free radical formation. Vitamin
      E, a strong antioxidant, functions as a free radical scavenger that potentially
      can suppress bone resorption while stimulating bone formation. Although the
      effects of vitamin E on immune functions are well documented, there is a paucity
      of information on its effect on skeletal health in vivo. The purpose of this
      study was to explore the influence of vitamin E supplementation on bone in young
      adult and old mice. Six and twenty-four month-old male C57BL/6NIA mice each were
      divided into two groups and fed a diet containing either adequate (30 mg/kg diet)
      or high (500 mg/kg diet) levels of vitamin E. Thirty days later, mice were killed
      and bones were removed for analyses including biomechanical testing using three
      point bending and mRNA expressions of insulin-like growth factor-I (IGF-I),
      osteocalcin, and type 1alpha-collagen using Northern blot. In old but not the
      young adult mice, high-dose vitamin E enhanced bone quality as evident by
      improved material and structural bone properties in comparison with adequate.
      This improved quality was accompanied by increases in bone dry weight, protein,
      and mRNA transcripts for osteocalcin, type Ialpha-collagen, and IGF-I. These data
      demonstrate that high-dose vitamin E has pronounced effects on bone quality as
      well as matrix protein in old mice by augmenting bone matrix protein without
      reducing bone mineralization as evidenced by unaltered bone density.

PMID- 12231426
TI  - L-tryptophan administration promotes the reversion of pre-established chronic
      liver injury in rats treated with carbon tetrachloride.
AB  - We examined the effect of L-tryptophan (Trp) administration on the reversion of
      CCl(4)-induced chronic liver injury after hepatotoxicant withdrawal in rats. When
      rats treated with CCl(4) twice a week for 6 weeks were released from CCl(4)
      treatment for 2 weeks, there was an incomplete reversion of liver injury. The
      reversion was enhanced by 2 weeks of daily intraperitoneal administration of Trp
      (50 mg/kg body weight), starting just after CCl(4) withdrawal. There were
      increases in the levels of thiobarbituric acid reactive substances, an index of
      lipid peroxidation, Ca(2+), triglycerides, and Trp, and decreases in tryptophan
      2,3-dioxygenase activity and serum triglyceride concentrations in the liver of
      rats treated with CCl(4) for 6 weeks. Serum albumin concentrations and in vitro
      hepatic protein synthesis activity did not change in the CCl(4)-treated rats. The
      changes in the CCl(4)-treated rats were partially attenuated 2 weeks after CCl(4)
      withdrawal. The attenuation was enhanced by 2 weeks of daily Trp administration.
      The increases in hepatic thiobarbituric acid reactive substances and
      triglycerides and the decreases in hepatic tryptophan 2,3-dioxygenase activity
      and serum triglyceride concentrations observed 2 weeks after CCl(4) withdrawal
      were almost completely attenuated by Trp administration. In vitro hepatic protein
      synthesis in CCl(4)-treated and untreated rats was increased by 2 weeks of daily
      Trp administration. These results indicate that Trp administration promotes the
      reversion of pre-established chronic liver injury in rats treated with CCl(4,)
      and suggest that Trp exerts this effect by enhancing the improvement of several
      parameters of liver dysfunction associated with chronic liver injury and by
      stimulating hepatic protein synthesis.

PMID- 12231427
TI  - Influence of an aggressive early enteral nutrition protocol on nitrogen balance
      in critically ill children.
AB  - The objective was to determine stress related factors and nutritional indices
      affecting the nitrogen balance (NB) and the creatinine height index (CHI) in
      critically ill children on early enteral nutrition (EEN). Seventy-one
      consecutively enrolled critically ill children aged 2 to 204 months, requiring
      prolonged mechanical ventilation, were studied. All patients were on early
      intragastric nutrition (Nutrison Pediatric or Standard) from day 1 (energy intake
      equal to 1/2, 1, 5/4, 6/4 and 6/4 of the predicted basal metabolic rate on days 1
      5, respectively). Nitrogen balance and CHI changes determined efficacy. Study
      patients had severe depletion of somatic protein status on stress day 1 (CHI
      <60%) but they reached the normal range of somatic protein status at the end of
      the EEN, on post-stress day 5 (CHI >80%, p <.004). On day 1, none of the patients
      had positive NB but after 5 days of EEN, 44 (62%) had positive NB and only 27
      (38%) had negative NB (p <.0001). Multivariate stepwise regression analysis
      showed that only the difference of daily given-recommended dietary allowances
      protein and the total repleted energy were positively correlated (r(2) =.47, p
      <.001 and r(2) = 34, p =.003, respectively) and multiple organ system failure
      negatively correlated with the NB (r(2) = -.24, p <.03) on the 5th day of the EEN
      protocol. Our data suggest that achievement of positive protein and energy
      balance in relation to the basic metabolic rate using an aggressive EEN protocol
      improves NB during the acute phase of stress in 2/3 of critically ill children.

PMID- 12231428
TI  - Inhibition of group I metabotropic glutamate receptor responses in vivo in rats
      by a new generation of carboxyphenylglycine-like amino acid antagonists.
AB  - A series of novel group I metabotropic glutamate receptor (mGlu) antagonists have
      been designed on the basis of the 4-carboxyphenylglycine pharmacophore. The
      compounds are either mGlu1 receptor selective or equipotent for both mGlu1 and
      mGlu5 receptors and have IC(50) values ranging from 1 to 30 microM determined by
      phosphoinositide hydrolysis (PI) assay in vitro. All the compounds produced dose
      dependent inhibition of group I mGlu receptor agonist (RS)-3,5
      dihydroxyphenylglycine (DHPG)-induced limbic seizure responses in mice with
      ED(50) values ranging from 9 nmol for LY393053 to 138 nmol for LY339840 after
      intracerebroventricular injection and were more potent than the mGlu1 receptor
      antagonist 1-aminoindan-1,5-dicarboxylic acid (ED(50)=477 nmol). Further
      antagonist actions were also demonstrated in a model of (RS)-DHPG-induced PI
      hydrolysis in vivo such that LY367385 and the active cis isomer of LY393053
      produced dose-dependent inhibition of PI responses in both cerebellum and
      hippocampus. Cis LY393053 also inhibited hippocampal PI responses when
      administered intraperitoneally at a dose of 30 mg/kg. These compounds define a
      new series of group I mGlu receptor antagonists which may serve as useful
      experimental tools.

PMID- 12231429
TI  - Rat motoneuron cell death in development correlates with loss of N-methyl-D
      aspartate receptors.
AB  - New techniques were applied for maintaining viable motoneurons in rat cervical
      spinal cord slices to study electrical and morphological properties from
      postnatal day (PD) 2-49. Lucifer Yellow injections showed nine to 12, or more,
      viable motoneurons/slice at PD2, reduced to two to three in lamina IX by PD9. At
      PD2 and from PD14 onward healthy motoneurons were electrically similar to those
      of adults. Motoneurons exhibited variable electrical properties and morphology
      around PD5. They were sensitive to kainate and AMPA at all ages. The sensitivity
      to N-methyl-D-aspartate (NMDA) was significant at PD2, less at PD9 and virtually
      absent at PD14. Our observations suggest that NMDA receptors play a role in
      regulation of motoneuron survival in the early postnatal period, but are lost
      from adult motoneurons.

PMID- 12231430
TI  - Electroconvulsive shock increases the phosphorylation of amphiphysin II in the
      rat cerebellum.
AB  - Amphiphysin II (Amph2) is known to undergo rapid dephosphorylation and
      phosphorylation at nerve terminals. After in vivo electroconvulsive shock (ECS)
      in the rat cerebellum, we found an electrophoretic mobility retardation of Amph2,
      which suggested an increased degree of phosphorylation above the non-stimulated
      level. This shifted signal was observed from 1 min, reached the maximum level at
      5 min and extended beyond 2 h after ECS. The shifted band was markedly decreased
      by the phosphatase treatment. Pretreatment with cyclosporin A augmented the
      mobility retardation of Amph2 after ECS. Our results indicate that ECS induces
      the phosphorylation of Amph2 in the rat cerebellum.

PMID- 12231431
TI  - Differential effects of muscimol upon the firing frequency of large and small
      amplitude antidromic dorsal root action potentials in rat spinal cord in vitro.
AB  - The effects of bath applied muscimol upon spontaneous and evoked antidromic
      activity recorded from lumbar dorsal roots was investigated in hemisected,
      isolated preparations of rat spinal cord. In magnesium free medium containing 0.1
      microM 4-aminopyridine, bursts of high amplitude (up to 1 mV), dorsal root
      reflexes were recorded. These were blocked by low concentrations of muscimol (2-5
      microM). Higher concentrations (5-20 microM) of muscimol caused a concentration
      dependent increase in the frequency of small amplitude (<200 microV) spontaneous
      dorsal root action potentials. The possibility that the large and small amplitude
      extracellular action potentials reflect activity in large and small diameter
      dorsal root axons, and that these respond in different ways to the GABA(A)
      agonist muscimol, is discussed.

PMID- 12231432
TI  - Non-linear dynamic complexity of the human EEG during meditation.
AB  - We used non-linear analysis to investigate the dynamical properties underlying
      the EEG in the model of Sahaja Yoga meditation. Non-linear dimensional complexity
      (DCx) estimates, indicating complexity of neuronal computations, were analyzed in
      20 experienced meditators during rest and meditation using 62-channel EEG. When
      compared to rest, the meditation was accompanied by a focused decrease of DCx
      estimates over midline frontal and central regions. By contrast, additionally
      computed linear measures exhibited the opposite direction of changes: power in
      the theta-1 (4-6 Hz), theta-2 (6-8 Hz) and alpha-1 (8-10 Hz) frequency bands was
      increased over these regions. The DCx estimates negatively correlated with theta
      2 and alpha-1 and positively with beta-3 (22-30 Hz) band power. It is suggested
      that meditative experience, characterized by less complex dynamics of the EEG,
      involves 'switching off' irrelevant networks for the maintenance of focused
      internalized attention and inhibition of inappropriate information. Overall, the
      results point to the idea that dynamically changing inner experience during
      meditation is better indexed by a combination of non-linear and linear EEG
      variables.

PMID- 12231433
TI  - Neuroprotective and antioxidant properties of FKBP-binding immunophilin ligands
      are independent on the FKBP12 pathway in human cells.
AB  - We focused on immunophilin isoforms in order to clarify the neuroimmunophilins
      which were identified as targets for the immunophilin ligands to elicit a
      neuroprotective effect. Although the expressions of five FK506-binding protein
      (FKBP) mRNAs were detected in both SH-SY5Y (human neuroblastoma) and U251 (human
      glioma) cell lysates, the FKBP12 mRNA expression was detected in only the SH-SY5Y
      cells, and not the U251 cells. However, we found that the SH-SY5Y and the U251
      cells were equipotent in the intensity of cellular protection of FK506 (an
      immunosuppressive immunophilin ligand) and GPI1046 (a non-immunosuppressive FK506
      analog), indicating that the protective effect and glutathione activation of
      FK506 and GPI1046 had little need to bind FKBP12. Therefore, we conclude that the
      neuroprotective and antioxidant properties of immunophilin ligands are
      independent on the FKBP12 pathway.

PMID- 12231434
TI  - Tissue-specific association of the human tyrosine hydroxylase gene with the
      nuclear matrix.
AB  - Association of the human tyrosine hydroxylase (TH) gene with the nuclear matrix
      was studied using bovine matrices from tissues differing in expression of the
      gene. An in vitro binding assay was performed with fragments encompassing the 
      2300/+2300 region of the human TH gene. All fragments bound to the nuclear matrix
      from the adrenal medulla but none bound to that from the liver. A computer search
      of the sequenced part of the studied region revealed putative matrix attachment
      regions (S/MAR) - one in the promoter and two in the first intron. The (TCAT)(n)
      microsatellite repeat included in one of the intronic S/MARs seems to influence
      the binding potential of the human TH gene to the nuclear matrices.

PMID- 12231435
TI  - Low levels of brain-derived neurotrophic factor and tyrosine kinase receptor B
      are related to loss of dentate granule cells after prolonged low-protein feeding
      in the rat.
AB  - Protein deprivation leads to neuronal and synaptic loss in the hippocampal
      formation, and to behavioral changes. We suggested that these effects could
      result from alterations in the levels of brain-derived neurotrophic factor (BDNF)
      and tyrosine kinase receptor B (TrkB). To investigate this issue, adult rats were
      submitted to protein deprivation for 6 months and compared with controls. The
      number of neurons of the dentate gyrus granular layer containing BDNF and TrkB
      was estimated from immunostained sections and the mRNA levels of BDNF and TrkB
      evaluated using in situ hybridization. After treatment, there was a loss of BDNF-
      and TrkB-immunoreactive cells and a reduction of the mRNA levels. Thus, it is
      likely that the decreased neurotrophic activity in the dentate gyrus of
      malnourished animals underpins neuronal degeneration and the ensuing behavioral
      alterations.

PMID- 12231436
TI  - Estrogen attenuates tumor necrosis factor-alpha expression to provide ischemic
      neuroprotection in female rats.
AB  - Proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) plays an
      important role in the pathogenesis of neurodegenerative diseases including
      ischemia. Circulating estrogen is positively associated with neuroprotection
      against ischemia in female rats. In the present study, we examined whether
      endogenous estrogen levels affect ischemia-induced TNF-alpha expression in normal
      cycling female rats. An elevated concentration of TNF-alpha was toxic to neurons.
      A high level of expression of TNF-alpha accompanied the decline in circulating
      estrogen levels in normal cycling female rats. Estrogen administration attenuated
      endotoxin-induced TNF-alpha expression and neuronal injury, indicating that the
      down-regulation of TNF-alpha expression plays a role in ischemic neuroprotection
      by estrogen. Therefore, we propose that one mechanism by which estrogen protects
      females from ischemic damage is through the regulation of TNF-alpha production.

PMID- 12231437
TI  - Restraint stress impaired maternal behavior in female mice lacking the neuromedin
      B receptor (NMB-R) gene.
AB  - Neuromedin B (NMB) is a bombesin-like peptide that exerts its function via NMB
      receptor (NMB-R). The NMB/NMB-R pathway is involved in the regulation of a wide
      variety of behaviors, such as spontaneous activity, feeding, and anxiety-related
      behavior. In the current study, we assessed the effects of stress on maternal
      behavior in female NMB-R-deficient mice. Non-stressed NMB-R-deficient and wild
      type mice showed normal maternal behavior. However, immediately after undergoing
      restraint-induced stress (30 min) both genotypes of mice exhibited severely
      decreased maternal behaviors. Furthermore, 30 min after stress induction,
      maternal behavior in wild-type mice recovered to near normal levels whereas that
      of NMB-R-deficient mice remained significantly lower. These results indicate that
      NMB-R-deficient mice suffer more severely from stress and suggest that
      dysfunction in the NMB/NMB-R pathway may constitute one of the risk factors of
      stress vulnerability.

PMID- 12231438
TI  - Paradoxical rise in brainstem PO(2) following umbilical cord occlusion in full
      term rat fetuses.
AB  - Although the fetus experiences severe hypoxia and ischemia during delivery, the
      fetal brain is protected from hypoxic-ischemic insults by unknown mechanisms. To
      investigate this phenomenon, fetal asphyxia was induced in pregnant rats by
      occlusion of the umbilical cord. Rather than producing cerebral hypoxia, the
      brainstem PO(2) of at-term fetuses increased following umbilical cord occlusion,
      while brainstem blood flow was markedly reduced. This paradoxical increase in
      brainstem PO(2) during asphyxia occurred in the majority of at-term fetuses, less
      frequently in fetuses 1 day prior to term and did not occur in animals following
      birth. Because occlusion of the umbilical cord prevents maternal delivery of
      oxygen to the fetus, we propose that the ability to maintain PO(2) is the result
      of pre-existing fetal stores of oxygen or from de novo generation of oxygen in
      the fetal brainstem.

PMID- 12231439
TI  - Dopamine modulation of activity of cat sensorimotor cortex neurons during
      conditioned reflexes.
AB  - The effects of iontophoretic application of dopamine and selective D1 or D2
      dopamine receptor agonists and antagonists on impulse activity of neurons of the
      deep layers of the sensorimotor cortex of cat were investigated during
      performance of a conditioned paw movement task. The application of dopamine,
      Quinpirole (selective D2 receptor agonist) or SKF 38393 (selective D1 receptor
      agonist) increased both background (P<0.001) and evoked impulse activity (P<0.05
      for selective agonists). Selective D2 and D1 receptor antagonists (Sulpiride and
      SKF 83566, respectively) both increased the latency of neural responses and
      significantly increased the latency of the conditioned paw movements (P<0.01).
      These data suggest that during natural physiological functions subcortical
      dopamine neurons provide facilitation of activity pyramidal neurons of
      sensorimotor cortex.

PMID- 12231440
TI  - Brain derived neurotrophic factor does not act on adult human cerebral
      endothelial cells.
AB  - Brain derived neurotrophic factor (BDNF), known to promote survival of neurons,
      has recently been involved in the regulation of endothelial cells and was shown
      to possess immunoregulatory properties. We therefore asked whether BDNF has
      immunoregulating effects in human cerebral endothelial cells (HCEC). Adult HCEC
      expressed vascular cell adhesion molecule-1 and HLA class II following
      stimulation with tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma,
      respectively, but not after BDNF treatment. Addition of BDNF did not modulate the
      effects of TNF-alpha and IFN-gamma on HCEC, including TNF-alpha induced
      interleukin-8. Fluorescent activated cell sorting, RT-PCR, and
      immunohistochemistry indicated that HCEC do not express the trkB or p75 receptors
      involved in BDNF signaling. These results demonstrate that adult HCEC are not a
      likely target for BDNF. Novel factors regulating HCEC remain to be identified.

PMID- 12231441
TI  - Unilateral trigeminal anaesthesia modifies postural control in human subjects.
AB  - The influence of trigeminal afferences on postural stabilization was tested.
      Twenty-seven subjects were recruited to evaluate the impact of trigeminal
      disturbance on orthostatic postural control before and after unilateral truncular
      anaesthesia of the mandibular nerve. Balance control quality was assessed using
      static posturography by means of statokinesigrams and lateral deviation. Postural
      control monitored by measuring the area covered by the centre of foot pressure
      decreases after anaesthesia in the eyes open condition. Postural deviation in the
      eyes closed condition was observed after anaesthesia in the controlateral side of
      anaesthesia. These data document the effects of trigeminal afferences on postural
      stabilization.

PMID- 12231442
TI  - Apoptotic positive cells in Krabbe brain and induction of apoptosis in rat C6
      glial cells by psychosine.
AB  - Globoid cell leukodystrophy (GLD) is an autosomal recessive disorder of infants,
      caused by deficient activity of cerebroside-beta-galactosidase resulting in loss
      of myelin accompanied by loss of oligodendrocytes. The loss of oligodendrocyte
      population is accompanied by accumulation of psychosine, which is considered as
      the molecule responsible for the observed pathophysiology of GLD. We were able to
      detect apoptotic cells by terminal dUTP nick-end labeling assay and nuclear
      localization of p53 in postmortem brain tissue of Krabbe's disease patients,
      which were not detected in the control brain. To study the role of psychosine in
      cell death, we investigated the effect of psychosine on C6 glial cell survival by
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Similar to
      ceramide (43.8% loss) the galactopsychosine and glucopsychosine treatment killed
      up to 46.3 and 48.75% of cells, respectively. On the other hand, sphingosine had
      no effect. DNA laddering assay confirmed these results. Moreover, psychosine
      induced detection of annexin-V positive cells supports a role for psychosine in
      C6 glial cell death via the apoptotic pathway. These results indicate that
      psychosine may play a role in apoptotic cell loss observed in GLD brain.

PMID- 12231443
TI  - Pallidal activity recorded in patients with implanted electrodes predictively
      correlates with eventual performance in a timing task.
AB  - Here we seek to establish whether there are activities in the human pallidum that
      may predict a specific aspect of performance, timing. When recording from two
      patients with Parkinson's disease and primary generalised dystonia following
      functional neurosurgery we found that the amplitude of oscillatory pallidal
      activity occurring prior to the completion of a bimanual timing task was strongly
      correlated with eventual task duration. The frequency of this oscillatory
      activity was around 25 Hz. We conclude that the human pallidum may be involved in
      the prediction of movement timings and that such internal estimates may be
      reflected in amplitude modulation of oscillatory activity around 25 Hz.

PMID- 12231444
TI  - Enantioselective metabolism of the designer drugs 3,4
      methylenedioxymethamphetamine ('ecstasy') and 3,4-methylenedioxyethylamphetamine
      ('eve') isomers in rat brain and blood.
AB  - The metabolism of MDA (3,4-methylenedioxyamphetamine), HMMA (3-hydroxy-4
      methoxymethylamphetamine) and HME (3-hydroxy-4-methoxyethylamphetamin) of the
      popular designer drugs MDMA ('ecstasy', 3,4-methylenedioxymethamphetamine) and
      MDE ('eve', 3,4-methylenedioxyethylamphetamine) was determined in rat serum,
      whole blood and urine, as well as in whole brain structures (cortex and striatum)
      after subcutaneous administration of 20 mg/kg MDMA and MDE, respectively. MDMA
      and MDE were extracted from serum and homogenized brain structures using a solid
      phase extraction procedure. The extracts were examined by a validated high
      performance liquid chromatography procedure coupled with fluorimetric detection.
      Our results demonstrate that MDMA is metabolized to a higher degree than MDE,
      resulting in a higher concentration of neurotoxic dihydroxymetabolites and (S)
      MDA. There was no difference between the metabolism of MDMA and MDE and its
      respective isomers. Different concentrations of the respective isomers of MDMA
      and MDE let us suggest an enantioselective metabolism for both MDMA and MDE.

PMID- 12231445
TI  - Association between the low molecular weight cytosolic acid phosphatase gene
      ACP1*A and comorbid features of Tourette syndrome.
AB  - Protein tyrosine phosphatases have been implicated in the regulation of
      serotonergic and dopaminergic activity in the central nervous system. In a recent
      study we found that nonA/nonA homozygosity at the locus codifying for the low
      molecular weight protein tyrosine phosphatase (ACP1) was associated with
      increased rates of major depression in males (P<0.00003), suggesting that the
      ACP1*A single nucleotide polymorphism (SNP) may be an important marker for
      psychopathology. In the present study we examined the ACP1*A SNP in 539 screened
      controls and 184 male Tourette syndrome (TS) cases, all Caucasians of European
      descent. The frequency of the nonA allele was markedly increased in TS cases
      relative to controls (P<0.0005), but this difference was restricted to cases with
      comorbid attention-deficit hyperactivity disorder (P<0.0001) and conduct disorder
      (P<0.0002), while having little relevance to TS itself.

PMID- 12231447
TI  - Effects of hippocampus-induced prefrontal long-term depression on gamma-band
      local field potential in anesthetized rats.
AB  - To determine whether long-term depression (LTD) affects cortical gamma-band local
      field potential (40-100 Hz), we conducted a LTD induction experiment in the
      hippocampus-prefrontal cortex (PFC) pathway of an anesthetized rat. The LTD
      induction increased the spontaneous level of PFC gamma-band power of 70-100 Hz,
      which was not affected after the long-term potentiation (LTP) induction in our
      previous experiment. In addition, the LTD induction increased the evoked PFC
      gamma-band power at 900 ms after hippocampal test stimulation; this latency
      appeared to differ from that (500-700 ms) observed in our previous LTP
      experiment. The results indicate that the PFC field potential increases its gamma
      band power following both LTP and LTD in the hippocampus-PFC pathway, which is
      involved in working memory. Particularly, the sustained increase by LTD may
      reflect a representation of working memory.

PMID- 12231446
TI  - The tau locus is not significantly associated with pathologically confirmed
      sporadic Parkinson's disease.
AB  - Mutations of the tau gene in frontotemporal dementia with parkinsonism and
      genetic association of the tau locus with progressive supranuclear palsy and
      corticobasal degeneration directly implicate the tau gene in the aetiology of
      these tauopathies. Three studies have also shown an association of the tau locus
      with clinically diagnosed Parkinson's disease. Noting the significant incidence
      of clinical misdiagnosis of Parkinson's disease, we investigated this tau gene
      association in a series of 157 pathologically confirmed cases of brain stem Lewy
      body Parkinson's disease by analysing their tau haplotype status. Although H1H1
      homozygotes are elevated in the Parkinson's disease cases (63.1%) compared to
      controls (56.1%) this difference is not significant (P=0.22). These results
      indicate that any association must either be weak (with an odds ratio of less
      than 2) or that previous positive associations were due to contamination of
      clinically diagnosed cases with other diagnostic clinico-pathological entities
      such as neurofibrillary tangle Parkinson's syndrome.

PMID- 12231448
TI  - Effect of chronic thyroxine treatment on catalepsy in rats.
AB  - The effect of chronic thyroid hormone (thyroxine, T4) administration on the
      duration of cataleptic freezing was studied in males of random-bred Wistar and
      genetic cataleptic (GC) rat strains. It was found that thyroidectomy brought
      about a sharp increase in immobility time in Wistar rats. Replacement with 0.015
      mg/kg per day of T4 for 30 days from the day after thyroidectomy prevented the
      development of predisposition to catalepsy, whereas the same dose of T4 failed to
      attenuate the predisposition to catalepsy in the case of a month delay between
      the thyroidectomy and the beginning of treatment. A chronic administration of T4
      at a dose of 0.1 mg/kg per day clearly decreased the genetically determined high
      expression of cataleptic reaction in GC rats. The results are evidence of the
      involvement of T4 in the regulation of cataleptic freezing and suggest that
      predisposition to catalepsy may be caused or enhanced by a deficit of thyroid
      hormone.

PMID- 12231449
TI  - An association study of a functional catalase gene polymorphism, -262C-->T, and
      patients with Alzheimer's disease.
AB  - According to the oxidative stress hypothesis which has been proposed as one of a
      number of possible mechanisms underlying pathogenesis of Alzheimer's disease
      (AD), accumulation of hydrogen peroxide in the brain of affected individuals, due
      to overproduction and/or insufficient detoxification, can trigger a cascade of
      neurotoxic events, thus contributing to the neuronal damage characteristic of the
      disease. The upregulation of enzymes that are able to neutralize hydrogen
      peroxide (catalase, peroxidases) would then be conceivably able to offer at least
      some protection from the damaging effects of this agent. In this study we
      examined the distribution of a functional polymorphism in the gene for catalase, 
      262C-->T, in an independent population of 137 AD patients and 130 control
      individuals. The presence of the polymorphism, which results in the elimination
      of a SmaI restriction site, was tested with a PCR amplification/SmaI digestion
      based assay. No significant difference has emerged from the comparison of either
      genotype or allele frequencies (P>0.5). We conclude that the catalase gene -262C-
      >T polymorphism does not confer a protective effect with respect to AD.

PMID- 12231450
TI  - Hyperbaric oxygenation prevented brain injury induced by hypoxia-ischemia in a
      neonatal rat model.
AB  - The occurrence of hypoxia-ischemia (HI) during early fetal or neonatal stages of
      an individual leads to the damaging of immature neurons resulting in behavioral
      and psychological dysfunctions, such as motor or learning disabilities, cerebral
      palsy, epilepsy or even death. No effective treatment is currently available and
      this study is the first to use hyperbaric oxygen (HBO) as a treatment for
      neonatal HI. Herein, we sought out to determine if HBO is able to offer
      neuroprotectivity against an HI insult. Seven-day-old rat pups were subjected to
      unilateral carotid artery ligation followed by 2.5 h of hypoxia (8% O(2) at 37
      degrees C). HBO treatment was administered by placing pups in a chamber (3 ATA
      for 1 h) 1 h after hypoxia exposure. Brain injury was assessed based on
      ipsilateral hemispheric weight divided by contralateral hemispheric weight, light
      microscopy, and EM. Sensorimotor functional tests were administered at 5 weeks
      after hypoxia exposure. After HI, the ipsilateral hemisphere was 52.65 and 57.64%
      (P<0.001) of the contralateral hemisphere at 2 and 6 weeks, respectively. In HBO
      treated groups, the ipsilateral hemisphere was 77.77 and 84.19% (P<0.001) at 2
      and 6 weeks. There was much less atrophy and apoptosis in HBO treated animals
      under light or electron microscopy. Sensorimotor function was also improved by
      HBO at 5 weeks after hypoxia exposure (Chi-square, P<0.050). The results suggest
      that HBO is able to attenuate the effects of HI on the neonatal brain by reducing
      the progression of neuronal injury and increasing sensorimotor function.

PMID- 12231451
TI  - Protein kinase C mediates potentiation of synaptic transmission by phorbol ester
      at parallel fibers in the dorsal cochlear nucleus.
AB  - Many cells in the outer two layers of the dorsal cochlear nucleus (DCN) express
      high levels of the phospholipid-activated, calcium dependent kinase, protein
      kinase C (PKC), an enzyme that can phosphorylate numerous proteins involved in
      neurotransmission and postsynaptic signaling. We investigated the effects of
      stimulating PKC with phorbol esters (phorbol 12-13 diacetate; PDAc) on parallel
      fiber synaptic transmission in brain slices of the guinea pig DCN. Phorbol esters
      increased the amplitude of the postsynaptic components of the field potential,
      including the excitatory post-synaptic field potential (fEPSP) and the population
      spike following electric stimulation of parallel fibers. Phorbol esters
      simultaneously decreased paired-pulse facilitation, suggesting that transmitter
      release mechanisms were affected. Potentiation of synaptic transmission and
      diminished paired-pulse potentiation were also observed in intracellular
      recordings of DCN neurons. The effects of phorbol esters were antagonized by the
      specific PKC blockers bisindolylmaleimide and calphostin C. Although modulation
      of the synaptic potentials appears to be mediated by presynaptic PKC, the
      differential effects of PDAc on the fEPSP and the population spike also suggest
      the involvement of postsynaptic PKC and postsynaptic targets. These experiments
      demonstrate that protein kinase C is capable of profoundly modulating synaptic
      transmission at parallel fiber synapses in the DCN.

PMID- 12231452
TI  - The presence of delta and mu-, but not kappa or ORL(1) receptors in bovine
      pinealocytes.
AB  - Physicians have noted since antiquity that their patients complained of less pain
      and required fewer analgesics at night-time. In humans, the circulating levels of
      melatonin, a pineal substance with analgesic and hypnotic properties, exhibit a
      pronounced circadian rhythm with serum levels being high at night and low during
      day-time. Moreover, pinealectomy abolishes the analgesic effects of melatonin,
      and naloxone disrupts the day-night rhythm of nociception. In this study, we have
      attempted to identify and characterize the nature and types of opioid receptor in
      bovine pinealocyte membranes, using a radioligand binding technique with the
      selective radioligands [3H]DAMGO, [3H]DPDPE, [3H]U69593 and [3H]orphanin-FQ (OFQ)
      for identifying mu (mu)-, delta (delta)-, kappa (kappa)- and opioid receptor-like
      (ORL(1)) receptors, respectively. The saturation experiments on bovine
      pinealocyte membranes for [3H]DPDPE binding provided B(max) and K(d) values of
      553+/-24 fmol/mg protein and 1.3+/-0.6 nM; and for [3H]DAMGO binding provided
      B(max) and K(d) values of 6.3+/-1.3 fmol/mg protein and 1.2+/-0.4 nM,
      respectively. On the other hand, the specific radioligands ([3H]U69593 and
      [3H]OFQ) binding of kappa and ORL(1) receptors were undetectable in bovine
      pinealocyte membranes. Furthermore, competitive experiments with opioid agonist
      and antagonist and related compounds confirmed the presence of mu- and delta
      opioid binding sites in bovine pinealocyte membranes. These results indicate that
      neither kappa nor ORL(1) receptors are present on the pinealocytes, and the
      majority of opioid receptors found in the bovine pineal gland are delta
      (possibly, both delta(1) and delta(2)) types, with a minority being mu type, and
      that both are primarily located on the bovine pinealocyte membranes. These opioid
      receptors, by stimulating the activity of N-acetyltransferase, enhance the
      synthesis of melatonin.

PMID- 12231453
TI  - Stress-induced mitochondrial depolarization and oxidative damage in PSP cybrids.
AB  - Increased oxidative damage and mitochondrial dysfunction have been suggested to
      play critical roles in the pathogenesis of progressive supranuclear palsy (PSP)
      yet the specific intracellular defects which cause and can result from these
      oxidative and bioenergetic defects remain unclear. To extend our previous PSP
      cybrid findings, we measured electron transport chain (ETC) activities in cell
      lines expressing mitochondrial genes from patients with PSP. Further, we measured
      changes in mitochondrial membrane potential as well as lipid peroxidation in PSP
      and control cybrids in response to mitochondrial toxins. We observed significant
      decreases in complex I+III activity in PSP cybrids as well as significant
      increases in markers of lipid oxidative damage as compared to control cybrids.
      These results coupled with previous reports from this and other laboratories
      strongly suggest contributory roles of mitochondrial dysfunction and oxidative
      damage in PSP, possibly due to genetic abnormalities and/or damage of
      mitochondrial DNA.

PMID- 12231454
TI  - Age-dependent changes in nitric oxide synthase activity and protein expression in
      striata of mice transgenic for the Huntington's disease mutation.
AB  - Huntington's disease (HD) is an autosomal hereditary neurodegenerative disorder
      caused by an abnormal expansion of the CAG repeats that code for a polyglutamine
      tract in a novel protein called huntingtin (htt). Both patients and experimental
      animals exhibit oxidative damage in specific areas of the brain, particularly the
      striatum. Nitric oxide (NO) is involved in many different physiological
      processes, and under pathological conditions it may promote oxidative damage
      through the formation of the highly reactive metabolite peroxynitrite; however,
      it may also play a role protecting cells from oxidative damage. We previously
      showed a correlation between the progression of the neurological phenotype and
      striatal oxidative damage in a line of transgenic mice, R6/1, which expresses a
      human mutated htt exon 1 with 116 CAG repeats. The purpose of the present work
      was to explore the participation of NO in the progressive oxidative damage that
      occurs in the striata of R6/1 mice. We analyzed the role of NO by measuring the
      activity of nitric oxide synthase (NOS) in the striata of transgenic and control
      mice at different ages. There was no difference in NOS activity between
      transgenic and wild-type mice at 11 weeks of age. In contrast, 19-week-old
      transgenic mice showed a significant increase in NOS activity, compared with same
      age controls. By 35 weeks of age, there was a decrease in NOS activity in
      transgenic mice when compared with wild-type controls. NOS protein expression was
      also determined in 11-, 19- and 35-week-old transgenic mice and wild-type
      littermates. Our results show increased neuronal NOS expression in 19-week-old
      transgenic mice, followed by a decreased level in 35-week-old mice, compared with
      controls, a phenomenon that parallels the changes in NOS enzyme activity. The
      present results suggest that NO is involved in the process leading to striatal
      oxidative damage and that it is associated with the onset of the progressive
      neurological phenotype in mice transgenic for the HD mutation.

PMID- 12231455
TI  - Repeated, intermittent treatment with amphetamine induces neurite outgrowth in
      rat pheochromocytoma cells (PC12 cells).
AB  - Repeated, intermittent treatment with amphetamine (AMPH) leads to long-term
      neurobiological adaptations in rat brain including an increased number and
      branching of dendritic spines. This effect depends upon several different cell
      types in the intact brain. Here we demonstrate that repeated, intermittent AMPH
      treatment induces neurite outgrowth in cultured PC12 cells without the
      requirement for integrated synaptic pathways. PC12 cells were treated with 1
      micro M AMPH for 5 min a day, for 5 days. After 10 days of withdrawal, there was
      an increase in the percentage of cells with neurites ( approximately 30%) and the
      length of neurites as well as an increase in the level of GAP-43 and
      neurofilament-M. Neurite outgrowth was enhanced as withdrawal time was increased.
      Neurite outgrowth was much greater following repeated, intermittent treatment
      with AMPH compared to continuous or single treatment with AMPH. Pretreatment with
      cocaine, a monoamine transporter blocker, inhibited the AMPH-mediated increase in
      neurite outgrowth. Neither NGF antibody nor DA receptor antagonists blocked AMPH
      induced neurite outgrowth, demonstrating that AMPH-induced neurite outgrowth is
      not dependent on endogenous NGF release or DA receptors. Thus we have
      demonstrated that repeated, intermittent treatment with AMPH has a neurotrophic
      effect in PC12 cells. The effect requires the action of AMPH on the
      norepinephrine transporter, and shares characteristics in its development with
      other forms of sensitization but does not require an intact neuroanatomy.

PMID- 12231456
TI  - Low intensity pain reported during elicitation of the H-reflex: no effects of
      trait anxiety and high intensity cycling exercise.
AB  - The aims of the experiment were to describe the intensity of pain perceptions
      experienced in response to elicitation of the H-reflex and examine the roles of
      trait anxiety and high intensity cycling exercise on those pain responses. Males
      (n=24) with high (n=12) or low (n=12) trait anxiety provided ratings of pain
      intensity in response to elicitation of the H-reflex before and after: resting
      for 20 min, cycling for 20 min at a high intensity (75% of peak oxygen
      consumption), or cycling for 20 min at a low intensity (40% of peak oxygen
      consumption). The results indicated that (i). low intensity pain was experienced
      during the elicitation of the H-reflex; (ii). high trait anxious males did not
      report more pain during the elicitation of the H-reflex, and (iii). there was no
      effect of high intensity cycling exercise on reducing post-exercise pain
      intensity associated with H-reflex elicitation. It is concluded that elicitation
      of the H-reflex reliably results in a low intensity pain.

PMID- 12231457
TI  - Effects of temperature and volume on intraperitoneal saline-induced changes in
      blood pressure, nociception, and neural activity in the rostroventral medulla.
AB  - ON and OFF cells of the rostral ventromedial medulla are hypothesized to modulate
      nociception with ON cells facilitating pain and OFF cells inhibiting pain. The
      current study analyzed the effects of intraperitoneal saline at different volumes
      and temperatures on nociception (tail flick reflex), blood pressure, and the
      activity of ON and OFF cells in lightly anesthetized rats. At large volumes (20
      cc/kg), room temperature saline excited 7/11 ON cells and inhibited 10/12 OFF
      cells for 2-5 min. In contrast, large volumes (20 cc/kg) of body temperature
      saline (37 degrees C) excited only 1/10 ON cells and inhibited only 3/13 OFF
      cells, and small volumes (1-2 cc/kg) of room temperature saline excited only 3/10
      ON cells and inhibited only 4/11 OFF cells. Tail flick latency increased
      following saline administration at large volumes with a significant effect of
      time, but not temperature. The excitation of ON cells and inhibition of OFF cells
      indicate that cold intraperitoneal saline could be painful and the increase in
      tail flick latency may indicate a diffuse noxious inhibitory control. It is also
      possible that the changes in ON and OFF cell activity caused a hyperalgesia that
      was masked by a simultaneous hypoalgesia that was mediated independent of the ON
      and OFF cells. Because intraperitoneal saline may produce pain or hyperalgesia,
      care should be used when saline is used experimentally or clinically.

PMID- 12231458
TI  - Regulation of neuropeptide Y in the rat amygdala following unilateral olfactory
      bulbectomy.
AB  - While the mechanisms are not fully understood, olfactory bulbectomy (OBX) is a
      well-known rat model of depression and depression-related disorders such as
      anxiety and aggression. Alterations in neuropeptide Y (NPY) levels in the brain
      have been linked to depression and have been shown to be involved in the response
      to stress. This study explored the possible regulation of NPY immunoreactivity in
      specific regions of the amygdala 14 days after OBX in adult male Sprague-Dawley
      rats (n=6). Unilateral OBX and immunohistochemistry permitted comparisons of NPY
      in the ipsilateral amygdala with NPY in the contralateral (sham) amygdala. OBX
      resulted in significant increases (P<0.05) in NPY immunoreactivity in the
      anterior medial amygdala (threefold) and the posterior medial amygdala (2.5
      fold). These regions receive projections from the accessory olfactory bulb (AOB).
      In contrast, the anterior and posterolateral cortical nuclei of the amygdala
      receive projections from the main olfactory bulb (MOB). NPY was not increased in
      these nuclei. These data show that not only does OBX increase NPY
      immunoreactivity in the amygdala, but also suggest that the AOB plays a prominent
      role in this regulation.

PMID- 12231459
TI  - Olfactory identification and apolipoprotein E epsilon 4 allele in mild cognitive
      impairment.
AB  - To investigate olfactory identification and apolipoprotein E epsilon 4 allele in
      patients with mild cognitive impairment (MCI), we used Cross-Cultural Smell
      Identification Test (CC-SIT) from University of Pennsylvania to assess olfactory
      identification performance and polymerase chain reaction (PCR) to detect
      apolipoprotein E epsilon 4 (ApoE epsilon 4) allele in 28 patients with MCI and
      the 30 age-matched control subjects in present study. The Mann-Whitney U test
      demonstrated that the MCI group performed significantly worse on CC-SIT than the
      normal aging group (P<0.01). For MCI patients olfaction scores correlated
      positively with CAMCOG-C (r=0.61, P<0.01), but not with age, gender or years of
      education. In normal subjects, the CC-SIT score showed no significant
      associations with age, gender, years of education, or CAMCOG-C. As the least
      common allele in Chinese, epsilon 4 was found in 13.3% of controls and in 35.8%
      of MCI in this study. ApoE epsilon 4 was significantly higher in MCI group than
      normal group (chi(2)=4.65, P<0.01). There was a significant effect of allele
      status on odor identification: subjects with epsilon 4 allele were not able to
      identify as many odors as the subjects without epsilon 4 allele (P<0.01). These
      results suggested that the decreased olfactory identification in MCI may be a
      marker for the early diagnosis of Alzheimer's disease, and ApoE genotype may be
      part of the basis of olfactory identification decline.

PMID- 12231460
TI  - Neurofilament L gene is not a genetic factor of sporadic and familial Parkinson's
      disease.
AB  - Mutations in two genes, alpha-synuclein and parkin, have been identified as some
      rare causes for familial Parkinson's disease (PD). alpha-Synuclein and parkin
      protein have subsequently been identified in Lewy bodies (LB). To gain further
      insight into the pathogenesis of PD we investigated the role of neurofilament
      light (NF-L), another component of LB aggregation. A detailed mutation search of
      the NF-L gene in 328 sporadic and familial PD patients of German ancestry
      revealed three silent DNA changes (G163A, C224T, C487T) in three unrelated
      patients. Analysis of the promoter region of the NF-L gene identified a total of
      three base pair substitutions defining five haplotypes. Association studies based
      on these haplotypes revealed no significant differences between PD patients and
      344 control individuals. Therefore, NF-L is unlikely to play a major role in the
      pathogenesis of PD.

PMID- 12231461
TI  - Brain metabolic effects of Neotrofin in patients with Alzheimer's disease.
AB  - Neotrofin, a reported inducer of CNS neurotrophic factor synthesis and release,
      with memory-enhancing activity and demonstrated restoration of age-induced memory
      deficits in animals, was tested in patients with mild to moderate Alzheimer's
      disease. Nineteen subjects were treated with 1 week of low-dose (150 mg per day)
      and 1 week of high-dose (500 or 1000 mg per day) Neotrofin. Cognitive composite
      scores demonstrated improvement in memory (F=9.6, P=0.0004), executive
      functioning (P=0.004), and attention (P=0.004). PET scanning was obtained before,
      after low, and after high dosing. The brain areas most affected were the
      cerebellum, and sensory and prefrontal cortices, where increases in GMR (Glucose
      Metabolic Rate) were observed. Increases and decreases were observed in the
      posterior superior temporal (BA 22), parahippocampal, inferior temporal (BA 37,
      20), and fusiform gyri as well as the superior parietal lobule and postcentral
      gyrus. There were strong hemispheric differences, producing opposite metabolic
      effects in homologous brain regions. Subcortically, the posterior thalamic
      region, meso-pontine tegmentum, and tectum had increases in GMR on the left side.
      At the low dose, GMR was generally increased, but to a lesser degree. The brain
      areas subserving memory, attention and executive functions were significantly
      altered in GMR by Neotrofin; however, the directions of these changes were
      complex. There were significant correlations between improvement in memory and
      executive function in brain areas involved in circuits subserving these
      functions. Thus, Neotrofin appears to induce metabolic changes in brain regions
      involved in circuits underlying memory, attention, and executive functioning.

PMID- 12231462
TI  - Differential effects of phospholipase inhibitors on free fatty acid efflux in rat
      cerebral cortex during ischemia-reperfusion injury.
AB  - Free fatty acid (FFA) elevation in the brain has been shown to correlate with the
      severity of damage in ischemic injury. The etiology of this increase in FFA
      remains unclear and has been hypothesized to result from phospholipase
      activation. This study examines the effects of specific phospholipase inhibitors
      on FFA efflux during ischemia-reperfusion injury. A four-vessel occlusion model
      of cerebral ischemia was utilized to assess the effects of PLA(2) and PLC
      inhibitors on FFA efflux from rat cerebral cortex. In addition, FFA efflux from
      non-ischemic cortices exposed to PLA(2) and PLC was measured. Concentrations of
      arachidonic, docosahexaenoic, linoleic, myristic, oleic, and palmitic acids in
      cortical superfusates were determined using high performance liquid
      chromatography (HPLC). Exposure to the non-selective PLA(2) inhibitor 4
      bromophenylacyl bromide (BPB) significantly inhibited FFA efflux during ischemia
      reperfusion injury (P<0.01 arachidonic, oleic and palmitic; P<0.05 all others);
      exposure to the PLC inhibitor U73122 had no observed effect. The effects of the
      Ca(2+)-dependent PLA(2) inhibitor arachidonyl trifluoromethyl ketone (AACOCF(3))
      mirrored the effects of BPB and led to reductions in all FFA levels (P<0.01
      arachidonic, oleic and palmitic; P<0.05 all others). Exposure to the secretory
      PLA(2) inhibitor 3-(3-acetamide-1-benzyl-2-ethyl-indolyl-5-oxy) propane sulfonic
      acid (LY311727) and to the Ca(2+)-independent PLA(2) inhibitor bromoenol lactone
      (BEL) had only minimal effects on FFA efflux. Application of both PLA(2) and PLC
      to non-ischemic cortices resulted in significant increases in efflux of all FFA
      (P<0.05). The study suggests that FFA efflux during ischemia-reperfusion injury
      is coupled to activation of Ca(2+)-dependent PLA(2) and provides further evidence
      of the potential neuroprotective benefit of Ca(2+)-dependent PLA(2) inhibitors in
      ischemia.

PMID- 12231463
TI  - Non-ocular dermal photoreception in the pond snail Lymnaea stagnalis.
AB  - Based on the results of previous behavioral experiments, researchers believe that
      sensitivity to light stimuli is not restricted to the eyes in the pond snail
      Lymnaea stagnalis. To determine the presence of a non-ocular dermal
      photoreception system and to examine the synaptic connections between this
      peripheral system and the central nervous system, we electrophysiologically
      examined the activities of the pedal nerves in L. stagnalis by light stimulation.
      The results demonstrated that light stimulation evokes non-ocular dermal
      photosensitive responses in the foot, that these responses exert inhibitory,
      afferent influences through the inferior pedal nerves to the pedal ganglia, and
      that these responses were independent of the ocular photoreception system in L.
      stagnalis.

PMID- 12231464
TI  - Concurrent formation of peroxynitrite with the expression of inducible nitric
      oxide synthase in the brain during middle cerebral artery occlusion and
      reperfusion in rats.
AB  - Peroxynitrite is assumed to play a crucial role in brain damage associated with
      the overproduction of nitric oxide (NO). The purpose of this study is to examine
      time-dependent changes of nitrite and nitrate (NOx) concentration in the
      circulation, and peroxynitrite formation as well as the expression of inducible
      nitric oxide synthase (iNOS) in the penumbra of rat brains during transient
      middle cerebral artery occlusion (MCAO) of Wistar rat for 2 h and reperfusion for
      4-70 h. NOx concentration in the circulation was continuously monitored at the
      right jugular vein by microdialysis. The expression of iNOS was detected at 22-70
      h after reperfusion in vascular walls and the cortex. Nitrotyrosine, a marker of
      peroxynitrite, appeared 4 h after reperfusion in the cortex, increasing
      substantially at 22-46 h in vascular walls. NOx level in dialysate increased
      immediately after MCAO. After a gradual decrease, the level increased again 4 h
      after reperfusion, reaching a maximum at 46 h. Brain myeloperoxidase activity, a
      marker of neutrophil infiltration, was not detected 4 h after reperfusion, but
      greatly increased at 22 h and then decreased. These results suggest that a marked
      increase of NOx level in the circulation might reflect the expression of iNOS,
      while neuronal NOS may contribute to peroxynitrite formation in the cortex
      observed at an earlier phase of reperfusion. This study indicates that monitoring
      NOx level in the circulation serves to assess the progress of stroke, and to
      determine appropriate therapeutic measures.

PMID- 12231466
TI  - ATP modulation of large conductance Ca(2+)-activated K(+) channels via a
      functionally associated protein kinase A in CA1 pyramidal neurons from rat
      hippocampus.
AB  - Using inside-out configuration of patch clamp techniques, ATP modulation of
      BK(Ca) channels was studied in hippocampal CA1 pyramidal neurons of adult rat.
      Intracellular ATP application markedly increased BK(Ca) channel activity, and
      this ATP-produced increase in BK(Ca) channel activity was characterized by a
      higher opening frequency with no changes in channel open times. In the presence
      of specific inhibitor against protein kinase A, H-89, ATP did not induce any
      increase in the channel activity. Furthermore, adding H-89 after addition of ATP
      reversed the modulation produced by ATP. In contrast, protein kinase C inhibitor
      chelerythrine exerted no apparent effects on ATP-induced channel activation. The
      present study suggests that BK(Ca) channels from hippocampal CA1 pyramidal
      neurons could be modulated by ATP via a functionally associated protein kinase A
      like protein.

PMID- 12231465
TI  - Calcium channel subtypes on single GABAergic presynaptic terminal projecting to
      rat hippocampal neurons.
AB  - High voltage-activated Ca(2+) channel subtypes triggering GABA release from nerve
      terminals (boutons) projecting to rat hippocampal CA1 pyramidal neurons were
      studied. Evoked GABAergic inhibitory postsynaptic currents (eIPSCs) were recorded
      in response to focal stimulation of single boutons in mechanically dissociated
      neurons and in response to stimulation of nerve bundle in slice preparations.
      Nilvadipine (3 micro M), an L-type Ca(2+) channel blocker, completely inhibited
      eIPSCs evoked by stimulation of single boutons, but had no effect on eIPSCs
      evoked by stimulation of nerve bundle at low frequencies. Nilvadipine (3 micro M)
      did, however, prevent the potentiation of eIPSC amplitude following high
      frequency stimulation of nerve bundles in the slice preparation. omega-Conotoxin
      GVIA (3 micro M), an N-type Ca(2+) channel blocker, and omega-agatoxin-IVA (0.3
      micro M), a P/Q-type Ca(2+) channel blocker, completely inhibited single bouton
      evoked eIPSCs in 33.3 and 83.3% of recordings, respectively. In response to low
      frequency nerve bundle stimulation in the slice preparation, omega-conotoxin-GVIA
      (3 micro M), omega-agatoxin-IVA (0.1 micro M) both partially reduced eIPSC
      amplitude, with the residual component being abolished by Cd(2+) (0.1 mM). From
      these results, the following hypotheses could be drawn. (1). The distribution of
      P/Q- and N-type channels at a single bouton is nonuniform. (2. When a focal
      stimulation is applied to a single bouton, L-type channels play a significant
      role in a generation of an action potential which subsequently activates P/Q- and
      N-type channels at GABA release sites. (3). Action potentials conducted through
      axons in the slice preparation are sufficient to depolarize the bouton membrane,
      even when L-type channels are suppressed.

PMID- 12231467
TI  - Effect of a 5-HT(2C) serotonin agonist, dexnorfenfluramine, on amyloid precursor
      protein metabolism in guinea pigs.
AB  - Stimulation of serotonin receptor subtypes 5-HT(2A) or 5-HT(2C) in stably
      transfected 3T3 cells by dexnorfenfluramine (DEXNOR) or serotonin increases
      secretion of the APP metabolite APP(s). It is not known whether activation of
      these receptors can also affect APP metabolism in vivo. We examined the effects
      of a single intraperitoneal (i.p.) injection of DEXNOR on APP(s) levels in
      cerebrospinal fluid (CSF) of guinea pigs. These levels were significantly
      (P<0.05) increased by a single dose of DEXNOR (1-4 mg/kg); those of the APP
      metabolites Abeta(1-40) and Abeta(1-42) were unaffected. The DEXNOR-induced (1
      mg/kg) increases in CSF APP(s) were suppressed by ritanserin (1 mg/kg) but not by
      ketanserin (2 mg/kg). When given alone, ritanserin did not affect CSF levels of
      APP(s), Abeta(1-40), or Abeta(1-42). Chronic treatment with DEXNOR for 9 days (1
      mg/kg bid, i.p.) increased CSF APP(s) levels, measured 2 h after the last
      injection (P<0.05), and decreased those of CSF Abeta(1-42) (P<0.05). Neither
      hippocampal nor cortical levels of the APP holoprotein (APP(h)), nor body weight,
      were affected by DEXNOR. Chronic administration of mCPP (1-(m
      chlorophenyl)piperazine) (2 mg/kg bid, i.p.), a 5-HT(2B/2C) agonist, for 9 days
      also increased CSF APP(s) levels (P<0.5) when measured 2 h after the drug's last
      administration; hippocampal and cortical APP(h) levels were unaffected. However,
      mCPP also caused a significant decrease in body weight gain. These data indicate
      that the pharmacological activation of 5-HT(2C) receptors can stimulate CSF
      APP(s) secretion and reduce Abeta production in vivo. Hence 5-HT(2C) receptors,
      which apparently are localized to the brain, may represent useful targets for the
      development of treatments for Alzheimer's disease.

PMID- 12231468
TI  - Lack of central effects of peripherally administered adenosine A(1) agonists on
      synaptic transmission in the rat hippocampus.
AB  - Peripheral administration of adenosine A(1) receptor selective agonists is
      generally thought to protect the hippocampus against ischemic damage via central
      actions. We examined the effects of two peripherally administered A(1) agonists,
      cyclohexyladenosine (CHA) and adenosine amine congener (ADAC), on synaptic
      transmission in the hippocampus and on indices of cardiovascular function. We
      conclude that the permeability of these agonists is not sufficient to result in
      concentrations necessary to activate central adenosine A(1) receptors within the
      hippocampus.

PMID- 12231469
TI  - Lesions of periventricular tissue surrounding the anteroventral third ventricle
      (AV3V) attenuate salivation and thermal tolerance in response to a heat stress.
AB  - The purpose of this study was to determine if ablation of the periventricular
      tissue that surrounds the anteroventral third ventricle (AV3V) would reduce an
      animal's ability to withstand a thermal challenge. The results show that AV3V
      lesion rats are less capable of withstanding a 37 degrees C heat stress and that
      this is, at least in part, due to a reduced salivation response.

PMID- 12231471
TI  - Methods to map protein interactions in mammalian cells: different tools to
      address different questions.
AB  - In the post-genome era, functional annotation of the predicted gene-sets will be
      one of the most important upcoming challenges. So-called interactome analysis
      positions a protein in its subcellular environment by mapping its interaction
      partners. Such interaction maps are essential for an accurate insight into
      protein function since many cellular processes are organised to operate in
      protein complexes. These assemblies have dynamic structures and can interact with
      each other, two properties which are often controlled by regulated protein
      expression and modification. Various methods exist to unravel protein interaction
      circuitries, which can be roughly divided into biochemical and genetic
      strategies. In this review we focus on the different strategies to study protein
      protein interactions in living mammalian cells. Recently developed analytical and
      screening methods are also addressed.

PMID- 12231473
TI  - Dose-effect of interleukin-10 and its immunoregulatory role in Crohn's disease.
AB  - BACKGROUND: Interleukin-10 (IL-10) is currently being extensively studied in
      clinical trials for the treatment of Crohn's disease (CD). Only marginal effects
      have, however, been reported, and the dose-response curve was bell-shaped
      contrasting with the reported data from in vitro experiments. AIM: To use another
      in vitro model to analyze the effect of rhIL-10 and rhIL-4 on the spontaneous
      mucosal TNF-alpha secretion in patients with CD, and to characterize the
      phenotype of the cells targeted by rhIL-10. METHODS: Non-inflamed colon biopsies
      from CD patients were cultured for 16 hours in presence of different
      concentrations of rhIL-10 or rhIL-4. The numbers of TNF-alpha-secreting cells
      among isolated lamina propria mononuclear cells (LPMNC) were estimated by
      Elispot. RESULTS: Both rhIL-10 and rhIL-4 down-regulate TNF-alpha secretion by
      LPMNC from CD patients, with a more pronounced effect with rhIL-10. These effects
      were closely linked to the cytokine concentrations used, with a bell-shaped dose
      response curve. Residual TNF-alpha secretion, in the presence of optimal rhIL-10
      concentration was mainly attributable to CD3+ T cells. In contrast, at higher
      rhIL-10 concentrations, CD3- cells contributed significantly to the TNF-alpha
      secretion. CONCLUSIONS: The in vitro model we used, demonstrates that IL-4, but
      mostly IL-10, efficiently suppresses TNF-alpha secretion in LPMNC from CD
      patients, with a dose-response curve similar to results obtained in vivo.
      Resistance at high rhIL-10 concentrations was associated with a change in the
      phenotype of TNF-alpha-secreting cells.

PMID- 12231472
TI  - Absence of endogenous interleukin-10 enhances the evolution of acute lung injury.
AB  - Interleukin-10 (IL-10) exerts a wide spectrum of regulatory activities in the
      immune and inflammatory response. The aim of this study was to investigate the
      role of endogenous IL-10 on the modulation of the inflammatory response in mice
      subjected to carrageenan-induced lung injury. When compared to carrageenan
      treated IL-10 wild-type (WT) mice, carrageenan-treated IL-10 knock-out mice (IL
      10KO) mice experienced a higher rate of pleural exudation, and polymorphonuclear
      cell migration. Exudate levels of the pro-inflammatory cytokines tumour necrosis
      factor, interleukin-1beta and interleukin-6 were also greatly enhanced in IL-10KO
      mice in comparison to wild-type mice. Lung myeloperoxidase (MPO) activity was
      significantly reduced in IL-10WT mice when compared to IL-10KO mice-treated with
      carrageenan. The degree of oxidative and nitrosative damage was significantly
      higher in IL-10KO mice than in wild-type littermates, as indicated by elevated
      malondialdehyde levels and formation of nitrotyrosine and poly (ADP-ribose)
      synthetase (PARS). Staining of lung tissue sections obtained from carrageenan
      treated IL-10WT with an anti-COX-2 antibody showed a positive staining of the
      inflamed tissue. Furthermore, expression of inducible nitric oxide synthase
      (iNOS) was found mainly in the macrophages of the inflamed lungs from carrageenan
      treated IL-10WT mice. The intensity and degree of the staining for COX-2 and iNOS
      were markedly enhanced in tissue sections obtained from carrageenan-treated IL
      10KO mice. Most notably, the degree of lung injury caused by carrageenan was also
      enhanced in IL-10KO mice. Taken together, our results clearly demonstrate that
      endogenous IL-10 exerts an anti-inflammatory role during acute inflammation and
      tissue damage associated with carrageenan-induced pleurisy, possibly by
      regulating neutrophil recruitment, and the subsequent cytokine and oxidant
      generation.

PMID- 12231474
TI  - Expression of genes for cytokines and cytokine-related functions in leukocytes
      infected with Herpes simplex virus: comparison between resistant and susceptible
      mouse strains.
AB  - Cytokines and chemokines play an important role in the first line of defence
      against viral infections. Moreover, these groups of proteins also contribute
      significantly to regulation of the acquired immune response. Therefore, knowledge
      of the expression of cytokines, chemokines and factors involved in their action
      may provide information about the immune reaction responsible for elimination of
      viral infections and for immune-mediated pathology. Using cDNA arrays, we have
      evaluated the expression of cytokines and genes related to cytokine function in
      resting murine peritoneal cells and in inflammatory macrophages infected with
      Herpes simplex virus (HSV)-1 and -2. To allow comparison, the experiments were
      performed using both the resistant mouse strain C57BL/6 and the susceptible
      strain BALB/c. The work identified a group of genes that is differentially
      expressed during HSV infection of cells from the two strains. Another group of
      genes was affected by HSV-1 but not HSV-2 infection and vice versa. Further
      analysis of these genes may provide new information about host defense against
      viral infections and could also lead to identification of the molecular basis for
      the pathological differences between infections with HSV-1 and -2.

PMID- 12231475
TI  - Mycophenolic acid and methotrexate inhibit lymphocyte cytokine production via
      different mechanisms.
AB  - Mycophenolic acid (MPA) and methotrexate (MTX) are immunosuppressive drugs used
      for the treatment of various immunological disorders. MPA is an inhibitor of
      inosine monophosphate dehydrogenase and MTX is a folate antagonist that inhibits
      tetrahydrofolate reductase. Production of T cell cytokines in whole blood
      cultures, as well as in PBMC cultures, is inhibited by a low concentration of
      both drugs. Inhibition of cytokine production after monocyte stimulation was less
      evident. The mechanism by which inhibition is achieved is different for both
      drugs. Inhibition of T cell cytokine production by MPA was more profound and
      started earlier compared to the inhibition by MTX. MTX induced apoptosis in T
      cells that became activated, whereas MPA prevented activation of T cells by
      arresting the cell cycle in the G0/G1 phase. Addition of guanosine and adenosine
      can overcome this cell cycle arrest, even after several days. Furthermore MPA
      inhibited the expression of activation markers HLA-DR and CD71 on T cells. The
      observation that MTX cannot prevent T cell activation but induces apoptosis in
      activated T cells, and that MPA reversibly prevents activation of T cells could
      explain the immunosuppressive effects of both these drugs.

PMID- 12231476
TI  - Cytokine pattern in cystic fibrosis patients during antibiotic therapy and gene
      therapy using adenoviral vector.
AB  - Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic
      fibrosis transmembrane conductance regulator (CFTR) gene. Despite improvements in
      treatment, pulmonary disease still remains the primary cause of death among these
      patients. In order to introduce a normal CFTR gene copy into airway epithelial
      cells, adenoviral vectors (AV) have been developed. AV are known to induce an
      inflammatory reaction that limits transgene expression, and can be potentially
      harmful. No human study has clearly monitored simultaneously, systemic and local
      inflammatory reaction, during AV administration. We report here the levels of C
      reactive protein (CRP), interleukin (IL)-6, IL-8, tumor necrosis factor-alpha
      (TNF-alpha), and interleukin-1 receptor antagonist (IL-1Ra) in plasma and
      bronchoalveolar lavage fluid (BALF) from six cystic fibrosis patients receiving
      AV encoding CFTR (AdCFTR). AdCFTR was administered to three cohorts of two
      patients into the nose on day 0, at doses ranging from 105 to 4 x 108 plaque
      forming units (pfu), followed, on day 1, by aerosolization of 107 to 5.4 x 108
      pfu. In order to ensure that patients were in the best clinical condition, and to
      further attenuate the broncho-pulmonary inflammation secondary to bacterial
      infection, they received antibiotic therapy, two weeks prior to AdCFTR
      administration, until 9 to 11 days after. We found that antibiotics markedly
      decreased CRP, TNF-alpha, IL-6, IL-1Ra levels in blood. In BALF, antibiotics
      slightly decreased TNF-alpha levels but had no effect on IL-8 and IL-1Ra, while
      IL-6 levels increased. AdCFTR administration did not induce any systemic or local
      cytokine release. In both blood and BALF, CRP, IL-8, IL-1Ra, TNF-alpha decreased,
      while IL-6 levels increased between day -7 and day 3. One patient presented an
      asymptomatic increase of all parameters in the BALF on day 7. Twenty one days
      later, he displayed a clinical deterioration suggestive of an exacerbation. In
      conclusion, this study demonstrates that antibiotic administration tends to
      attenuate systemic but not local broncho-pulmonary inflammation in CF patients.
      In the setting of our study, AdCFTR administration did not induce cytokine
      release. Further studies are necessary to investigate other inflammatory markers
      and the mechanisms involved during AV-mediated gene transfer for a better
      understanding of the immune reaction, which continues to hamper the development
      of gene therapy for CF patients.

PMID- 12231477
TI  - Induction of interleukin-2 receptor alpha (IL-2Ralpha) expression by interleukin
      2: important role of the interleukin-2 receptor beta chain region between the two
      Stat5 docking sites.
AB  - The interleukin-2 receptor alpha (IL-2Ralpha) forms, together with IL-2Rbeta and
      gammac chains, a high affinity IL-2 receptor that is important for IL-2
      responsiveness and normal T cell function. Expression of the IL-2Ralpha gene by T
      cells is regulated mainly at the transcription level which is transiently
      activated by antigen and upregulated and then prolonged by stimulation with IL-2.
      The effect of IL-2 on the IL-2Ralpha gene depends on the activation of the
      transcription factor Stat5, which acts on an IL-2- responsive enhancer that
      consists of two Stat5 and an Elf1 binding site. To identify the functional
      domains of the IL-2 receptor required for the stimulation of IL-2Ralpha gene
      expression, we introduced, into the CTL44 T cell line, receptor chimeras between
      the extracellular domain of the IL-9 receptor and the cytoplasmic region of IL
      2Rbeta. Analyzing the effect of mutations in the intracellular IL-2Rbeta segment,
      we found that a minimal receptor containing the Jak boxes and one intact Stat5
      docking site (i.e. tyrosine 392 or 510) can, as expected, mediate Stat5
      activation, but is unable to stimulate IL-2Ralpha expression. However, when this
      minimal receptor includes the region between the two tyrosines, its capacity to
      mediate IL-2Ralpha cell surface expression is restored. These data suggest that
      the segment between the two Stat5 docking sites of the IL-2Rbeta chain mediates
      signaling events that, together with Stat5 activation, are essential for the
      stimulation of IL-2Ralpha gene transcription.

PMID- 12231478
TI  - Bronchopulmonary hyperreactivity and lung eosinophil sequestration but not their
      migration to the alveolar compartment are independent of interleukin-5 in
      allergic mice.
AB  - IL-5 is present in the lung and in the circulation following allergenic
      challenges in humans and in animals, but its role in bronchopulmonary
      hyperreactivity (BHR) and lung and bronchoalveolar lavage fluid (BALF)
      eosinophilia remains unclear. Because compartmentalization of IL-5 is recognized,
      the anti-IL-5 monoclonal antibody TRFK-5 or its isotype control GL113 were
      delivered selectively intranasally (i.n.) and/or intravenously (i.v.) before the
      prior i.n. challenge with 10 mug OVA in BALB/c and BP2 "Biozzi" mice immunized
      according to optimized protocols with read-outs taken 24 h later. IL-5 in the
      BALF was suppressed by i.n. TRFK-5, whereas its production persisted in the
      serum. Conversely, i.v. TRFK-5 suppressed IL-5 in the serum but not in the BALF.
      IL-5 was suppressed in conditioned medium from lung explants from mice treated
      with i.n. TRFK-5, which did not affect the other Th2 cytokines, IL-4 and IL-13.
      IL-5 is thus present in the alveolar, pulmonary and circulatory compartments
      following an i.n. allergenic challenge. When specific anti-IL-5 antibodies were
      delivered by the same i.n. route, BALF eosinophilia was markedly reduced, whereas
      BHR and lung eosinophil sequestration persisted totally or mostly, in both
      strains. The passage of eosinophils from lungs to alveoli depends on IL-5
      released into the BALF, but not into circulation, whereas their lung
      sequestration and BHR are mostly IL-5-independent. IL-5 alone does not account
      for the complexities of BHR or of eosinophil tissue trapping, and lung-targeted
      immunobiologicals should be delivered into the appropriate compartment in order
      to assess the role of specific mediators in experimental airways/lung allergy.

PMID- 12231479
TI  - Complex network of cytokines activating murine microglial cell activity against
      Acanthamoeba castellani.
AB  - In the central nervous system, cytokine-primed microglia play a pivotal role in
      host defence against Acanthamoeba castellani infections. In this study, the
      effect of rIL-1beta, rIL-6 or rTNF-alpha, combined or not with rIFN-gamma, on A.
      castellani infection of murine microglia was examined. Priming of microglial
      cells with either rIL-1beta or rIL-6, in the presence or absence of rIFN-gamma,
      triggered amebastatic activity, while the treatment of microglia with rTNF-alpha
      plus rIFN-gamma additively triggered, in a dose-dependent fashion, amebicidal
      activity. Inasmuch as NGMA affected cytokine-triggered anti-parasitic activity
      during the priming process, the NO-dependent pathway itself appears not to be
      directly involved in the anti-amebic capacities. These data suggest that the
      proinflammatory cytokines IL-1beta, IL-6 or TNF-alpha could trigger anti
      microbial activity against A. castellani infection in the brain.

PMID- 12231480
TI  - The mechanism by which interleukin-1 beta reduces net fluid absorption from the
      rat colon.
AB  - IL-1beta is suspected to be involved in the diarrhea that always accompanies
      inflammatory bowel disease. This work was aimed at studying the in vivo effect of
      IL-1beta on the net absorption of fluid, Na(+) and Cl(-) from the rat colon, and
      at delineating its mechanism of action. Rats were injected i.p. with IL-1beta (1
      mug/kg body weight) and the colon was perfused, four hours later, with Krebs
      Ringer buffer. Net fluid absorption was calculated as the difference between the
      total volume of the buffer infused and collected per cm(2) of perfused intestine.
      Chloride in both buffers was determined by titration according to Mohr's method
      and net Cl- absorption was calculated in the same way. IL-1beta reduced the net
      absorption of water and chloride. The cytokine also reduced the percentage
      recovery of the Na(+)-K(+) ATPase activity in crude homogenates of membranes from
      surface and crypt colonic cells as revealed by the determination of inorganic
      phosphate released. In addition IL-1beta decreased the protein expression of the
      Na(+)-K(+) pump and increased that of the NaKCl(2) symporter. It is concluded
      that IL-1beta has a dual effect: it inhibits the Na(+)-K(+) pump and consequently
      NaCl absorption, and up-regulates the NaKCl(2) transporter and increases Cl(-)
      secretion. The ultimate effect of the two processes is a net decrease in Na(+)+
      and Cl(-) absorption and an increase in water retention in the colon leading to
      the observed diarrhea in inflammatory bowel disease.

PMID- 12231481
TI  - Proinflammatory interferon-gamma--inducing monokines (interleukin-12, interleukin
      18, interleukin-15)--serum profile in patients with systemic lupus erythematosus.
AB  - Concentrations of three interferon-gamma - inducing monokines, IL-12, IL-18 and
      IL-15, were investigated in the serum of 60 patients with systemic lupus
      erythematosus (SLE) and 20 healthy subjects. IL-12 and IL-18 were detectable in
      the serum of all patients with SLE and in all healthy controls. The level of IL
      12 was significantly higher in SLE patients (median 264.9 pg/ml) than in the
      control group (median 163.6 pg/ml, p < 0.02). Similar differences were observed
      in the level of IL-18 (median values 602.2 pg/ml and 252.7 pg/ml, respectively, p
      < 0.001). Correlations between serum levels of IL-12 and IL-18 and SLE activity
      were not statistically significant (p > 0.05). We found a significant, positive
      correlation between IL-12 and IL-18 (rho = 0.419, p < 0.001) in SLE patients. The
      level of IL-18 was higher in the SLE patients with antinuclear antibodies (ANA)
      (median 660.0 pg/ml) than in ANA-negative patients (median 326.5 pg/ml, p <
      0.03), as well as in patients with immunoglobulin deposits at the dermal
      epidermal junction (median 746.0 pg/ml and 444.0 pg/ml respectively, p < 0.04).
      The level of IL-12 was also higher in patients with skin immunoglobulin deposits
      (328.9 pg/ml) than those without this phenomenon (257.0 pg/ml, p < 0.05). The
      levels of both cytokines in the patients treated with immunosuppressive drugs and
      those patients not treated were similar. The serum levels of IL-15 were low and
      not significant both in SLE patients (median 2.9 pg/ml), and in healthy controls
      (median 1.6 pg/ml). In conclusion, serum levels of IL-12 and IL-18 are higher in
      SLE patients than in healthy controls which may indicate a role in the disease
      pathogenesis. However, they do not correlate with disease activity and seem to be
      unresponsive to immunosuppressive treatment.

PMID- 12231482
TI  - A New York City firefighter: overwhelmed by World Trade Center dust.

PMID- 12231483
TI  - The incremental application of lung-protective high-frequency oscillatory
      ventilation.

PMID- 12231484
TI  - Muscle mass, not body weight, predicts outcome in patients with chronic
      obstructive pulmonary disease.

PMID- 12231485
TI  - CD8 cytotoxic T cells and the development of new tuberculosis vaccines.

PMID- 12231486
TI  - Interventional therapy for coronary artery disease.

PMID- 12231487
TI  - Acute eosinophilic pneumonia in a New York City firefighter exposed to World
      Trade Center dust.
AB  - We report a sentinel case of acute eosinophilic pneumonia in a firefighter
      exposed to high concentrations of World Trade Center dust during the rescue
      effort from September 11 to 24. The firefighter presented with a Pa(O2) of 53 mm
      Hg and responded to oxygen and corticosteroids. Computed tomography scan showed
      patchy ground glass density, thickened bronchial walls, and bilateral pleural
      effusions. Bronchoalveolar lavage recovered 70% eosinophils, with only 1%
      eosinophils in peripheral blood. Eosinophils were not degranulated and increased
      levels of interleukin-5 were measured in bronchoalveolar lavage and serum.
      Mineralogic analysis counted 305 commercial asbestos fibers/10(6) macrophages
      including those with high aspect ratios, and significant quantities of fly ash
      and degraded fibrous glass. Acute eosinophilic pneumonia is a rare consequence of
      acute high dust exposure. World Trade Center dust consists of large particle-size
      silicates, but fly ash and asbestos fibers may be found in bronchoalveolar lavage
      cells.

PMID- 12231488
TI  - High-frequency oscillatory ventilation for acute respiratory distress syndrome in
      adults: a randomized, controlled trial.
AB  - Observational studies of high-frequency oscillatory ventilation in adults with
      the acute respiratory distress syndrome have demonstrated improvements in
      oxygenation. We designed a multicenter, randomized, controlled trial comparing
      the safety and effectiveness of high-frequency oscillatory ventilation with
      conventional ventilation in adults with acute respiratory distress syndrome; 148
      adults with acute respiratory distress syndrome (Pa(O2)/fraction of inspired
      oxygen <or= 200 mm Hg on 10 or more cm H2O positive end-expiratory pressure) were
      randomized to high-frequency oscillatory ventilation (n = 75) or conventional
      ventilation (n = 73). Applied mean airway pressure was significantly higher in
      the high-frequency oscillation group compared with the conventional ventilation
      group throughout the first 72 hours (p = 0.0001). The high-frequency oscillation
      group showed early (less than 16 hours) improvement in Pa(O2)/fraction of
      inspired oxygen compared with the conventional ventilation group (p = 0.008);
      however, this difference did not persist beyond 24 hours. Oxygenation index
      decreased similarly over the first 72 hours in both groups. Thirty-day mortality
      was 37% in the high-frequency oscillation group and was 52% in the conventional
      ventilation group (p = 0.102). The percentage of patients alive without
      mechanical ventilation at Day 30 was 36% and 31% in the high-frequency
      oscillation and conventional ventilation groups, respectively (p = 0.686). There
      were no significant differences in hemodynamic variables, oxygenation failure,
      ventilation failure, barotraumas, or mucus plugging between treatment groups. We
      conclude that high-frequency oscillation is a safe and effective mode of
      ventilation for the treatment of acute respiratory distress syndrome in adults.

PMID- 12231490
TI  - Rapid screening for alpha1-antitrypsin deficiency in patients with chronic
      obstructive pulmonary disease using dried blood specimens.
AB  - We describe two reliable methods for high-throughput screening of proteinase
      inhibitor (PI) S and PI Z alpha(1)-antitrypsin (alpha(1)-AT) deficiency alleles
      from dried blood spot (DBS) specimens using the LightCycler fluorimetric
      analyzer. The method was used to study 72 patients with chronic obstructive
      pulmonary disease. Results were confirmed with DNA sequencing. The alpha(1)-AT
      concentration in DBS was determined with immune nephelometry. Sixteen patients
      (22%) showed no PI Z or PI S mutations. Five patients (7%) had a heterozygous
      genotype consisting of a PI S allele and a normal allele for the Z and S
      positions (non-S non-Z). Twenty-five patients (35%) had a heterozygous genotype
      consisting of a PI Z and a non-S non-Z allele. Two (3%) had the PI SS genotype, 2
      (3%) the PI SZ, and 20 (28%) the PI ZZ. All patients with two normal alpha(1)-AT
      alleles and 10 heterozygous carriers of one normal and one deficient allele had
      alpha(1)-AT levels that fell within the alpha(1)-AT DBS normal range (1.8-3.1
      mg/dl). Two patients with the rare PI MM(malton)- and PI MM(heerlen)-deficient
      variants showed deficient alpha(1)-AT levels; PI S and PI Z were not detected.
      Processing 32 samples requires only 40 minutes. This single-step, cost-effective
      technology is optimal for working with small amounts of DNA, as are present in
      DBS. The method is suitable for large-scale screening, in cases where PI type is
      important.

PMID- 12231489
TI  - Midthigh muscle cross-sectional area is a better predictor of mortality than body
      mass index in patients with chronic obstructive pulmonary disease.
AB  - This study was undertaken to test the hypothesis that a reduction in midthigh
      muscle cross-sectional area obtained by CT scan (MTCSA(CT)) is a better predictor
      of mortality in chronic obstructive pulmonary disease (COPD) than low body mass
      index (BMI). We also wished to evaluate whether anthropometric measurements could
      be used to estimate MTCSA(CT). One hundred forty-two patients with COPD (age = 65
      +/- 9 years, mean +/- SD, 26 F, BMI = 26 +/- 6 kg/m(2), FEV(1) = 42 +/- 16%
      predicted) were recruited from September 1995 to April 2000 with a mean follow-up
      of 41 +/- 18 months. The primary end-point was all-cause mortality during the
      study period. A Cox proportional hazards regression model was used to predict
      mortality using the following independent variables: age, sex, daily use of
      corticosteroid, FEV(1), DL(CO), BMI, thigh circumference, MTCSA(CT), peak
      exercise workrate, Pa(O2), and Pa(CO2). Only MTCSA(CT) and FEV(1) were found to
      be significant predictors of mortality (p = 0.0008 and p = 0.01, respectively). A
      second analysis was also performed with FEV(1) and MTCSA(CT) dichotomized.
      Patients were divided into four subgroups based on FEV(1) (< or >or= 50%
      predicted) and MTCSA(CT) (< or >or= 70 cm(2)). Compared with patients with an
      FEV(1) >or= 50% predicted and a MTCSA(CT) >or= 70 cm(2), those with an FEV(1) <
      50% predicted and a MTCSA(CT) >or= 70 cm(2) had a mortality odds ratio of 3.37
      (95% confidence interval, 0.41-28.00), whereas patients with an FEV(1) < 50%
      predicted and a MTCSA(CT) < 70 cm(2) had a mortality odds ratio of 13.16 (95%
      confidence interval, 1.74-99.20). MTCSA(CT) could not be estimated with
      sufficient accuracy from anthropometric measurements. In summary, we found in
      this cohort of patients with COPD that (1) MTCSA(CT) was a better predictor of
      mortality than BMI, and (2) MTCSA had a strong impact on mortality in patients
      with an FEV(1) < 50% predicted. These findings suggest that the assessment of
      body composition may be useful in the clinical evaluation of these patients.

PMID- 12231491
TI  - Augmentation of allergic early-phase reaction by nerve growth factor.
AB  - The allergic early-phase reaction, a hallmark of allergic bronchial asthma, is
      caused by allergen and immunoglobulin E-dependent mediator release from mast
      cells. It was previously shown that nerve growth factor (NGF) contributes to
      acute airway inflammation. This study further investigates the role of NGF in the
      allergic early-phase reaction using a well-established mouse model of ovalbumin
      induced allergic airway inflammation. Treatment of sensitized and aerosol
      challenged BALB/c mice with blocking anti-NGF antibodies inhibited allergen
      induced early-phase reaction and suppressed airway inflammation. Transgenic mice
      constitutively overexpressing NGF in the airways (Clara-cell secretory protein
      promoter [CCSP]-NGF-tg) were employed and compared with wild-type animals. In
      sensitized and challenged CCSP-NGF-tg mice, early-phase reaction, airway
      inflammation, as well as percental relative increases in serotonin levels were
      augmented compared with wild-type mice. These effects were paralleled by
      increased serotonin levels in the airways, whereas immunoglobulin E levels
      remained unaffected. Furthermore, CCSP-NGF-tg mice developed an increased
      reactivity of sensory neurons in response to inhaled capsaicin demonstrating NGF
      mediated neuronal plasticity. These data provide evidence for the functional role
      of NGF in the development of allergic early phase responses in the airways and
      the lung.

PMID- 12231492
TI  - The importance of prenatal exposures on the development of allergic disease: a
      birth cohort study using the West Midlands General Practice Database.
AB  - The etiology of allergic disease is not understood, but a decreased exposure to
      infection may play an important role. There are few published data on the impact
      of change in microbial exposure during pregnancy on the child's risk of
      developing allergic disease. Using a birth cohort of 24,690 children, derived
      from the West Midlands General Practice Research Database, we investigated a
      number of perinatal exposures on the incidence of asthma, eczema, and hay fever.
      Our findings suggest that exposure to antibiotics in utero is associated with an
      increased risk of asthma in a dose-related manner (more than two courses of
      antibiotics compared with none adjusted hazard ratio [HR] 1.68; 95% confidence
      interval [CI], 1.51-1.87), and similar associations are present for eczema
      (adjusted HR 1.17; 95% CI, 1.06-1.29) and hay fever (adjusted HR 1.56; 95% CI,
      1.22-2.01). Exposure to a range of infections in utero was also associated with a
      small increased risk of developing allergic disease. Strong protective effects of
      older siblings on the incidence of allergy are present within this cohort, but
      previous pregnancies that did not result in a live birth were not protective. Our
      findings suggest that exposure to antibiotics and to infections in utero is a
      potentially important risk factor in the development of allergic disease.

PMID- 12231493
TI  - Familial predisposition and cosegregation analysis of adult obstructive sleep
      apnea and the sudden infant death syndrome.
AB  - Previous studies suggest a familial link between adult obstructive sleep apnea
      syndrome (OSAS) and sudden infant death syndrome (SIDS). However, most of these
      studies were hampered by the availability of too few cases of SIDS to draw
      conclusions. To examine the familial nature of this association in Iceland,
      hospital-based lists of all patients who were diagnosed with OSAS (n = 2,350) and
      SIDS (n = 58) from 1979 to 1998 were used to separately determine the familial
      occurrence of OSAS and SIDS and to search for evidence of cosegregation of these
      conditions in Icelandic families, using a nationwide genealogy database. The risk
      ratio for a first-degree relative of a patient with OSAS was 2.0 (1.7-2.8, 95%
      confidence interval). The risk ratio of the more severely affected patients with
      OSAS was slightly higher (2.3). Likewise, the kinship coefficient (KC) for the
      OSAS patient group, which determines the relatedness of the patients, was
      significantly larger than the mean KC of 1,000 matched control groups. Estimation
      of the KC for the SIDS group showed a trend toward significance when compared
      with control groups, but after excluding one of the half-siblings in the SIDS
      group from the analysis, the difference did not show any trend toward
      significance. Although the results of the analysis of the relatedness between all
      patients with OSAS and infants who died of SIDS were not significant, a trend
      toward significance was evident when the data were separately analyzed for the
      more severely affected patients with OSAS. Collectively, these results
      demonstrate a strong familial component in OSAS and suggest that infants who died
      of SIDS may have shared some of the same susceptibility factors with OSAS.

PMID- 12231494
TI  - Outcome of patients with idiopathic pulmonary fibrosis admitted to the intensive
      care unit.
AB  - This retrospective study describes the clinical course of 38 patients with
      idiopathic pulmonary fibrosis (IPF) admitted to the intensive care unit (ICU).
      There were 25 males and 13 females who were the mean age of 68.3 +/- 11.5 years.
      Twenty patients were on corticosteroids at the time of admission to the hospital,
      and 24 had been on home oxygen therapy. The most common reason for ICU admission
      was respiratory failure. The Acute Physiology and Chronic Health Evaluation III
      predicted ICU and hospital mortality rates were 12% and 26%, whereas the actual
      ICU and hospital mortality rates were 45% and 61%, respectively. We did not find
      significant differences in pulmonary function or echocardiogram findings between
      survivors and nonsurvivors. Mechanical ventilation was used in 19 patients (50%).
      Sepsis developed in nine patients. Multiple organ failure developed in 14% of the
      survivors and in 43% of the nonsurvivors (p = 0.14). Ninety-two percent of the
      hospital survivors died at a median of 2 months after discharge. These findings
      suggest that patients with IPF admitted to the ICU have poor short- and long-term
      prognosis. Patients with IPF and their families should be informed about the
      overall outlook when they make decisions about life support and ICU care.

PMID- 12231495
TI  - Human dendritic cells presenting adenovirally expressed antigen elicit
      Mycobacterium tuberculosis--specific CD8+ T cells.
AB  - Previous studies in murine and human models have suggested an important role for
      CD8+ T cells in host defense to Mycobacterium tuberculosis (Mtb). Consequently, a
      successful tuberculosis vaccine may require the elicitation of sustained CD4+ and
      CD8+ T cell responses. We tested the hypothesis that the potent CD4+ T cell
      antigen Mtb39 is also a CD8+ T cell antigen. A recombinant adenovirus-expressing
      Mtb39 (adenoMtb39) was used to infect monocyte-derived dendritic cells. Using
      interferon-gamma enzyme-linked immunospot, Mtb39-specific CD8+ T lymphocytes were
      detected in three healthy individuals with latent tuberculosis infection who also
      had strong anti-Mtb39-specific CD4+ T cell responses. An Mtb39-specific CD8+ T
      cell line was generated using Mtb39-expressing dendritic cells. Mtb39-specific T
      cell clones were obtained by limiting dilution cloning. All seven T cell clones
      obtained were HLA-B44 restricted. Using a panel of synthetic overlapping peptides
      representative of Mtb39, the peptide epitope was identified for two clones.
      Furthermore, all T cell clones recognized Mtb-infected dendritic cells and were
      cytolytic. We conclude that infection of dendritic cells with adenoviral vectors
      expressing Mtb proteins allows for measurement of antigen-specific CD8+ T cell
      responses from peripheral blood mononuclear cells. The technique will be useful
      in defining CD8+ T cell antigens and in measuring immunogenicity of tuberculosis
      vaccines.

PMID- 12231496
TI  - Tumor necrosis factor-alpha is central to acute cigarette smoke-induced
      inflammation and connective tissue breakdown.
AB  - The role of tumor necrosis factor-alpha (TNF-alpha) as a mediator of cigarette
      smoke-induced disease is controversial. We exposed mice with knocked-out p55/p75
      TNF-alpha receptors (TNF-alpha-RKO mice) to cigarette smoke and compared them
      with control mice. Two hours after smoke exposure, increases in gene expression
      of TNF-alpha, neutrophil chemoattractant, macrophage inflammatory protein-2, and
      macrophage chemoattractant, protein-1 were seen in control mice. By 6 hours, TNF
      alpha, macrophage inflammatory protein-2, and macrophage chemoattractant protein
      1 gene expression levels had returned to control values in control mice and
      stayed at control values through 24 hours. In TNF-alpha-RKO mice, no changes in
      gene expression of these mediators were seen at any time. At 24 hours, control
      mice demonstrated increases in lavage neutrophils, macrophages, desmosine (a
      measure of elastin breakdown), and hydroxyproline (a measure of collagen
      breakdown), whereas TNF-alpha-RKO mice did not. In separate experiments, pure
      strain 129 mice, which produce low levels of TNF-alpha, showed no inflammatory
      response to smoke at 24 hours or 7 days. We conclude that TNF-alpha is central to
      acute smoke-induced inflammation and resulting connective tissue breakdown, the
      precursor of emphysema. The findings support the idea that TNF-alpha promoter
      polymorphisms may be of importance in determining who develops smoke-induced
      chronic obstructive pulmonary disease.

PMID- 12231497
TI  - Randomized crossover trial of two treatments for sleep apnea/hypopnea syndrome:
      continuous positive airway pressure and mandibular repositioning splint.
AB  - Mandibular repositioning splints (MRSs) and continuous positive airway pressure
      (CPAP) are used to treat the sleep apnea/hypopnea syndrome (SAHS). There are some
      data suggesting that patients with milder symptoms prefer MRS, but there are few
      comparative data on outcomes. Therefore, we performed a randomized crossover
      trial of 8 weeks of CPAP and 8 weeks of MRS treatment in consecutive new
      outpatients diagnosed with SAHS (apnea/hypopnea index [AHI] >or= 5/hour, and >or=
      2 symptoms including sleepiness). Assessments at the end of both limbs comprised
      home sleep study, subjective ratings of treatment value, sleepiness, symptoms,
      and well-being, and objective tests of sleepiness and cognition. Forty-eight of
      51 recruited patients completed the trial (12 women; age [mean +/- SD], 46 +/- 9
      years; Epworth 14 +/- 4; median AHI, 22/hour; interquartile ratio [IQR], 11
      43/hour). Significant (p <or= 0.01) differences between MRS and CPAP were
      observed for 7 of 21 variables (effect sizes, 0.3-0.6 SDs), all favoring CPAP,
      including AHI (15 +/- 16 and 8 +/- 6/hour, respectively), effectiveness rating,
      symptoms, Epworth (12 +/- 5 and 8 +/- 5, respectively), functional outcomes of
      sleepiness questionnaire, short-form 36 health survey mental component, and
      health transition scores. Objective sleepiness, cognitive performance, and
      preference for treatments were not different. In patients experiencing a mild
      form of the syndrome (AHI < 15, n = 18), symptoms, treatment efficacy and
      satisfaction, and subjective sleepiness were also better with CPAP than with MRS
      (effect sizes, 0.7-1.1 SDs). These results do not support these MRS devices as
      first-line treatment for sleepy patients with SAHS.

PMID- 12231498
TI  - Effect of vertical dimension on efficacy of oral appliance therapy in obstructive
      sleep apnea.
AB  - The aim of this study was to assess the effect of bite opening induced by a
      mandibular advancement splint (MAS) on efficacy and side effects in the treatment
      of obstructive sleep apnea. In a randomized crossover fashion, 23 adult patients
      received either MAS-1 (4 mm of interincisal opening) or MAS-2 (14 mm of
      interincisal opening) for 2 weeks, followed by the alternate treatment for 2
      weeks, with an intervening 1-week washout. Complete response was defined as a
      resolution of symptoms and a reduction in apnea/hypopnea index (AHI) to less than
      5 per hour. Partial response was defined as improved symptoms and a reduction in
      AHI of 50% or more, with the AHI remaining at a value of 5 or more per hour. Both
      MAS-1 and MAS-2 produced similar reductions in mean (+/- SEM) AHI from baseline:
      21 +/- 2 versus 8 +/- 1/hour and 21 +/- 2 versus 10 +/- 2/hour, respectively (p <
      0.001). Either complete response or partial response occurred in 74 and 61% of
      patients with MAS-1 and MAS-2, respectively. Subjective improvements were
      reported with both appliances by the majority of patients. Patients preferred MAS
      1 (78 versus 22%, p = 0.007). This study suggests that the amount of bite opening
      induced by MAS does not have a significant impact on treatment efficacy but does
      have an impact on patient acceptance.

PMID- 12231499
TI  - Bipolar radiofrequency thermal ablation of the soft palate in habitual snorers
      without significant desaturations assessed by magnetic resonance imaging.
AB  - Sleep-disordered breathing, including habitual snoring, is a major health
      problem. Treatment of primary habitual snoring should be individualized using
      both conservative and active treatment methods. Active surgical interventions
      are, however, associated with significant morbidity. Therefore, procedures
      causing far less morbidity should be preferred. Our aim was to assess the
      efficacy and acceptability of bipolar radiofrequency thermal ablation of the soft
      palate in habitual snorers without significant desaturations associated with
      excessive daytime sleepiness. We treated 20 nonobese habitual snorers (median
      age, 43 years, range 35-63). All the patients had the major site of obstruction
      at the level of the soft palate, and they were treated on an outpatient basis in
      two treatment sessions separated by 1 week. The pretreatment and post-treatment
      symptoms and findings as well as the overall efficacy of the procedure were
      evaluated by questionnaires, visual analogue scales, and magnetic resonance
      imaging. All the questionnaires showed a statistically significant change,
      indicating decreased snoring and daytime sleepiness. The magnetic resonance
      studies showed that the procedure induced notable T1-signal alterations in the
      treated tissue, and when compared with the pretreatment images, certain
      dimensions of the soft palate were significantly changed. Bipolar radiofrequency
      thermal ablation of the soft palate seems to be well tolerated and effective
      regarding primary habitual snorers without significant desaturations associated
      with excessive daytime sleepiness.

PMID- 12231500
TI  - Lung microvascular and arterial endothelial cells differ in their responses to
      intercellular adhesion molecule-1 ligation.
AB  - Neutrophil adherence to tumor necrosis factor-alpha (TNF-alpha)-treated human
      pulmonary microvascular endothelial cells (PMECs) induces cytoskeletal changes in
      endothelial cells that require intercellular adhesion molecule-1 (ICAM-1)
      dependent signaling events. This study determined whether similar changes
      occurred in rat PMECs and whether rat pulmonary arterial endothelial cells
      (PAECs) responded differently. Neutrophil adherence induced an increase in the
      formation of F-actin and in the apparent stiffness of TNF-alpha-treated rat
      PMECs. These responses, however, were absent in PAECs. To determine the
      mechanisms underlying these differences, ICAM-1-mediated signaling events were
      compared. Upregulation of ICAM-1 by TNF-alpha and redistribution of ICAM-1
      induced by cross-linking antibodies were similar in both cell types. However,
      neutrophil adherence induced production of reactive oxygen species only in PMECs
      and not in PAECs. Moreover, phosphorylation of p38 mitogen-activated protein
      kinase induced by ICAM-1 cross-linking occurred only in PMECs and not in PAECs.
      This increase in p38 phosphorylation in PMECs was inhibited by allopurinol, a
      xanthine oxidase inhibitor. These data demonstrated that whereas TNF-alpha
      upregulated ICAM-1 and ICAM-1 cross-linking induced a similar redistribution of
      ICAM-1 on the endothelial cell surface, ICAM-1 ligation initiated p38 activation
      and cytoskeletal rearrangements only in PMECs and not in PAECs. Thus, neutrophil
      adhesion through ICAM-1 induced signaling events leading to cytoskeletal changes
      only in PMECs, the site of neutrophil emigration and edema formation, and not in
      PAECs.

PMID- 12231501
TI  - Racing Alaskan sled dogs as a model of "ski asthma".
AB  - Athletes who play sports in cold weather, particularly skaters and cross-country
      skiers, have an increased prevalence of lower airway disease that is hypothesized
      to result from repeated penetration of incompletely conditioned air into the lung
      periphery. In this study, we investigated the hypothesis that canine winter
      athletes also suffer from increased prevalence of lung disease secondary to
      hyperpnea with cold air. Bronchoscopy and bronchoalveolar lavage was conducted in
      elite racing sled dogs 24 to 48 hours after completion of a 1,100-mile endurance
      race. Bronchoscopic abnormalities were classified as none, mild, moderate, or
      severe, based on the quantity and distribution of intralumenal debris. Eighty-one
      percent of the dogs (48 of 59) examined had abnormal accumulations of
      intralumenal debris, with 46% (27 of 59) classified as moderate or severe,
      indicating significant accumulation of exudate. Bronchoalveolar lavage obtained
      from dogs after the race had significantly higher nucleated macrophage and
      eosinophil counts compared with sedentary control dogs. Our findings support the
      hypothesis that strenuous exercise in cold environments can lead to lower airway
      disease and suggest that racing sled dogs may be a useful naturally occurring
      animal model of the analogous human disease.

PMID- 12231502
TI  - Allergen-induced increases in bone marrow T lymphocytes and interleukin-5
      expression in subjects with asthma.
AB  - Inhaled allergen challenge of subjects with atopic asthmatic increases bone
      marrow eosinophil progenitor cells. Interleukin-5 (IL-5) specifically induces
      growth and maturation of eosinophils. This study examined the effect of allergen
      challenge on the number of bone marrow total and CD3+ cells expressing IL-5
      protein and IL-5 mRNA in subjects with asthma who developed either allergen
      induced isolated early responses, or early and late asthmatic responses (dual
      responders). At 24 hours after allergen challenge, dual responders had
      significantly greater blood and airway eosinophilia compared with early
      responders. There were significant increases in the percentage of bone marrow
      CD3+ cells (p < 0.005) in both groups. However, there were significant
      differences in the increases in bone marrow IL-5 mRNA+ (p < 0.005), CD3+ (p <
      0.005), and IL-5 mRNA+ CD3+ (p < 0.005) cells between the dual and early
      responder groups. These results suggest that, in subjects with atopic asthma,
      inhaled allergen causes trafficking of T lymphocytes to the bone marrow, and that
      in subjects who develop late responses and greater blood and airway eosinophilia
      after inhalation of allergen, there is a significant increase in the ability of
      bone marrow cells, particularly T lymphocytes, to produce IL-5.

PMID- 12231503
TI  - Bleomycin sensitivity of mice expressing dominant-negative p53 in the lung
      epithelium.
AB  - The chemotherapeutic drug bleomycin causes DNA damage and apoptosis in the lungs
      of mice within hours of endotracheal instillation followed by inflammation and
      fibrosis weeks later. The p53 tumor suppressor protein mediates cellular
      responses to DNA damage, including induction of apoptosis, but the effects of p53
      activation in the various cell types of the lung during bleomycin-induced
      pulmonary fibrosis remain unclear. We show here that a transgene with a dominant
      negative mutant form of human p53 expressed from the surfactant protein C
      promoter sensitizes mice to bleomycin-induced lung injury. The bleomycin-exposed
      transgenic animals display more severe lung pathology with associated collagen
      deposition and more pronounced lung eosinophilia than simultaneously exposed
      nontransgenic littermates. These observations suggest that compromising p53
      function in the alveolar epithelium impairs recovery of the lung from bleomycin
      induced injury.

PMID- 12231504
TI  - A CaMK cascade activates CRE-mediated transcription in neurons of Caenorhabditis
      elegans.
AB  - Calcium (Ca2+) signals regulate a diverse set of cellular responses, from
      proliferation to muscular contraction and neuro-endocrine secretion. The
      ubiquitous Ca2+ sensor, calmodulin (CaM), translates changes in local
      intracellular Ca2+ concentrations into changes in enzyme activities. Among its
      targets, the Ca2+/CaM-dependent protein kinases I and IV (CaMKs) are capable of
      transducing intraneuronal signals, and these kinases are implicated in neuronal
      gene regulation that mediates synaptic plasticity in mammals. Recently, the
      cyclic AMP response element binding protein (CREB) has been proposed as a target
      for a CaMK cascade involving not only CaMKI or CaMKIV, but also an upstream
      kinase kinase that is also CaM regulated (CaMKK). Here, we report that all
      components of this pathway are coexpressed in head neurons of Caenorhabditis
      elegans. Utilizing a transgenic approach to visualize CREB-dependent
      transcription in vivo, we show that this CaMK cascade regulates CRE-mediated
      transcription in a subset of head neurons in living nematodes.

PMID- 12231505
TI  - Tailoring the activity of restriction endonuclease PleI by PNA-induced DNA
      looping.
AB  - DNA looping is one of the key factors allowing proteins bound to different DNA
      sites to signal one another via direct contacts. We demonstrate that DNA looping
      can be generated in an arbitrary chosen site by sequence-directed targeting of
      double-stranded DNA with pseudocomplementary peptide-nucleic acids (pcPNAs). We
      designed pcPNAs to mask the DNA from cleavage by type IIs restriction enzyme PleI
      while not preventing the enzyme from binding to its primary DNA recognition site.
      Direct interaction between two protein molecules (one bound to the original
      recognition site and the other to a sequence-degenerated site) results in a
      totally new activity of PleI: it produces a nick near the degenerate site. The
      PNA-induced nicking efficiency varies with the distance between the two protein
      binding sites in a phase with the DNA helical periodicity. Our findings imply a
      general approach for the fine-tuning of proteins bound to DNA sites well
      separated along the DNA chain.

PMID- 12231506
TI  - Serine phosphorylation of RUNX2 with novel potential functions as negative
      regulatory mechanisms.
AB  - The RUNX family represents a small group of heterodimeric transcription factors
      that master-regulate osteogenesis and hematopoiesis in mammals. Their genetic
      defects cause human diseases such as cleidocranial dysplasia (CCD) and acute
      myelogenous leukemia. However, the mechanism(s) regulating their functions are
      still poorly understood. Here, we report a novel observation that suggests that
      the osteogenesis-associated homologue RUNX2 is negatively regulated by the
      phosphorylation of two conserved serines (S104 and S451) in two distinct
      functional aspects. The phosphorylation of S104 could abolish the
      heterodimerization of RUNX2 with the partner subunit, PEBP2beta, which enhances
      the metabolic stability of RUNX2. On the other hand, the phosphorylation of S451
      resides within the C-terminal transcription inhibition domain of RUNX2 and hence
      is implicated in its functional mobilization. One CCD mutation, S104R of RUNX2,
      appears to mimic the phosphorylation-dependent inhibition of heterodimerization,
      thereby rendering RUNX2 metabolically unstable.

PMID- 12231507
TI  - Coordinated methyl and RNA binding is required for heterochromatin localization
      of mammalian HP1alpha.
AB  - In mammalian cells, as in Schizosaccharomyces pombe and Drosophila, HP1 proteins
      bind histone H3 tails methylated on lysine 9 (K9). However, whereas K9-methylated
      H3 histones are distributed throughout the nucleus, HP1 proteins are enriched in
      pericentromeric heterochromatin. This observation suggests that the methyl
      binding property of HP1 may not be sufficient for its heterochromatin targeting.
      We show that the association of HP1alpha with pericentromeric heterochromatin
      depends not only on its methyl-binding chromo domain but also on an RNA-binding
      activity present in the hinge region of the protein that connects the conserved
      chromo and chromoshadow domains. Our data suggest the existence of complex
      heterochromatin binding sites composed of methylated histone H3 tails and RNA,
      with each being recognized by a separate domain of HP1alpha.

PMID- 12231508
TI  - Depletion of MOM1 in non-dividing cells of Arabidopsis plants releases
      transcriptional gene silencing.
AB  - Mitotic and meiotic inheritance of epigenetic information is coupled to the
      reproduction of chromatin conformation and DNA methylation patterns. This implies
      that the S phase of the cell cycle provides a window of opportunity for changes
      in epigenetic determination. Recent studies, however, have suggested that
      chromatin structure is also rather dynamic in quiescent cells of multicellular
      eukaryotes and that silent heterochromatic regions can become accessible to
      transcription. Such epigenetic flexibility in differentiated tissues could be of
      physiological importance. The mechanisms and molecular components involved are of
      great interest but as yet unknown. We examined MOM1 (Morpheus' Molecule 1), a
      regulator of transcriptional gene silencing (TGS) that acts independently of DNA
      methylation, for its role in the maintenance of TGS in non-dividing,
      differentiated cells. The results provide evidence that TGS maintenance mediated
      by MOM1 is a dynamic process that can be modified in non-dividing cells of mature
      plant organs by depletion of MOM1.

PMID- 12231509
TI  - Composition of the central stalk of the Na+-pumping V-ATPase from Caloramator
      fervidus.
AB  - The Na+-pumping V-ATPase complex of the thermophilic bacterium Caloramator
      fervidus was purified and dissociated under controlled conditions. The structure
      of purified V1-ATPase subcomplexes differing in subunit composition was analyzed
      by electron microscopy and single particle analysis of 50 000 projections.
      Difference mapping of subcomplex projections revealed the presence and position
      of two subunits in the central stalk. A density with an elongated shape similar
      to the gamma subunit of F-ATPases is partly located within V1 and corresponds,
      most likely, to subunit E. Subunit E is connected to the membrane-bound part V0
      via subunit C, a spherical density that is connected to the center of V0. The
      presence of subunit C makes the central stalk substantially longer in comparison
      to the F-ATPases, in which the gamma subunit connects directly to F0.

PMID- 12231510
TI  - The FKBP12-rapamycin-associated protein (FRAP) is a CLIP-170 kinase.
AB  - CLIP-170/Restin belongs to a family of conserved microtubule (MT)-associated
      proteins, which are important for MT organization and functions. CLIP-170 is a
      phosphoprotein and phosphorylation is thought to regulate the binding of CLIP-170
      to MTs. However, little is known about the kinase(s) involved. In this study, we
      show that FKBP12-rapamycin-associated protein (FRAP, also called mTOR/RAFT)
      interacts with CLIP-170. CLIP-170 is phosphorylated in vivo at multiple sites,
      including rapamycin-sensitive and -insensitive sites, and is phosphorylated by
      FRAP in vitro at the rapamycin-sensitive sites. In addition, rapamycin inhibited
      the ability of CLIP-170 to bind to MTs. Our observations suggest that multiple
      CLIP-170 kinases are involved in positive and negative control of CLIP-170, and
      FRAP is a CLIP-170 kinase positively regulating the MT-binding behavior of CLIP
      170.

PMID- 12231511
TI  - The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle
      mediated secretory pathway.
AB  - HMGB1, a non-histone nuclear factor, acts extracellularly as a mediator of
      delayed endotoxin lethality, which raises the question of how a nuclear protein
      can reach the extracellular space. We show that activation of monocytes results
      in the redistribution of HMGB1 from the nucleus to cytoplasmic organelles, which
      display ultrastructural features of endolysosomes. HMGB1 secretion is induced by
      stimuli triggering lysosome exocytosis. The early mediator of inflammation
      interleukin (IL)-1beta is also secreted by monocytes through a non-classical
      pathway involving exocytosis of secretory lysosomes. However, in keeping with
      their respective role of early and late inflammatory factors, IL-1beta and HMGB1
      respond at different times to different stimuli: IL-1beta secretion is induced
      earlier by ATP, autocrinally released by monocytes soon after activation; HMGB1
      secretion is triggered by lysophosphatidylcholine, generated later in the
      inflammation site. Thus, in monocytes, non-classical secretion can occur through
      vescicle compartments that are at least partially distinct.

PMID- 12231512
TI  - To scan or not to scan, it is a question of timing: technetium-99m-annexin V
      radionuclide imaging assessment of treatment efficacy after one course of
      chemotherapy.

PMID- 12231513
TI  - Taxane analogues: distinguishing royal robes from the "Emperor's New Clothes".

PMID- 12231514
TI  - Min Chiu Li: a perspective in cancer therapy.

PMID- 12231515
TI  - Increased uptake of the apoptosis-imaging agent (99m)Tc recombinant human Annexin
      V in human tumors after one course of chemotherapy as a predictor of tumor
      response and patient prognosis.
AB  - PURPOSE: Many anticancer therapies exert their therapeutic effect by inducing
      apoptosis in target tumors. We evaluated in a Phase I study the safety and the
      feasibility of (99m)Tc-Annexin V for imaging chemotherapy-induced apoptosis in
      human cancers immediately after the first course of chemotherapy. EXPERIMENTAL
      DESIGN: Fifteen patients presenting with lung cancer (n = 10), lymphoma (n = 3),
      or breast cancer (n = 2) underwent (99m)Tc-Annexin V scintigraphy before and
      within 3 days after their first course of chemotherapy. Tumor response was
      evaluated by computed tomography and (18)F-fluoro-2-deoxy-D-glucose positron
      emission tomography scans, 3 months in average after completing the treatment.
      Median follow-up was 117 days. RESULTS: In all cases, no tracer uptake was
      observed before treatment. However, 24-48 h after the first course of
      chemotherapy, 7 patients who showed (99m)Tc-Annexin V uptake at tumor sites,
      suggesting apoptosis, had a complete (n = 4) or a partial response (n = 3).
      Conversely, 6 of the 8 patients who showed no significant posttreatment tumor
      uptake had a progressive disease. Despite the lack of tracer uptake after
      treatment, the 2 patients with breast cancer had a partial response. Overall
      survival and progression-free survival were significantly related to tracer
      uptake in treated lung cancers and lymphomas (P < 0.05). No serious adverse
      events were observed. CONCLUSIONS: Our preliminary results demonstrated the
      feasibility and the safety of (99m)Tc-Annexin V for imaging apoptosis in human
      tumors after the first course of chemotherapy. Initial data suggest that early
      (99m)Tc-Annexin V tumor uptake may be a predictor of response to treatment in
      patients with late stage lung cancer and lymphoma.

PMID- 12231516
TI  - Maintenance biotherapy for metastatic melanoma with interleukin-2 and granulocyte
      macrophage-colony stimulating factor improves survival for patients responding to
      induction concurrent biochemotherapy.
AB  - PURPOSE: A prospective Phase II study of a novel maintenance biotherapy regimen
      after induction biochemotherapy was conducted in patients with metastatic
      melanoma in efforts to maintain responses and improve survival. EXPERIMENTAL
      DESIGN: Thirty-three patients with poor prognosis metastatic melanoma who
      achieved a partial response (PR) or stable disease (SD) to induction concurrent
      biochemotherapy were treated with chronic low-dose interleukin (IL)-2 and
      granulocyte macrophage-colony stimulating factor, and intermittent pulses of
      intermediate/high-dose decrescendo IL-2 over a 12-month period. The outcome of
      these patients was compared with a control group of patients at our institution
      who were treated recently with induction biochemotherapy and achieved a PR or SD.
      RESULTS: Five patients (15%) achieved a complete response, and 4 patients (12%)
      maintained SD for at least 6 months on maintenance biotherapy. The median
      progression-free survival (PFS) and overall survival (OS) were 8.1 months and
      18.5 months, respectively, compared with historical controls, which were PFS 5.9
      months (P = 0.0015) and OS 9.3 months (P = 0.0004). Administration of maintenance
      biotherapy was a significant predictor of PFS (P = 0.0008) and OS (P = 0.0001) in
      multivariate and matched-pair analyses (P = 0.002). The maintenance biotherapy
      regimen was well tolerated with no dose-limiting acute or cumulative toxicities.
      CONCLUSION: In this single institution study, maintenance biotherapy with IL-2
      and granulocyte macrophage colony-stimulating factor in patients achieving PR or
      SD to induction biochemotherapy improved PFS and OS compared with historical
      controls. A larger multicenter Phase II trial has been initiated in an effort to
      confirm these results.

PMID- 12231517
TI  - Safety and immunogenicity of a DNA vaccine encoding carcinoembryonic antigen and
      hepatitis B surface antigen in colorectal carcinoma patients.
AB  - Despite an abundance of preclinical data, relatively little is known regarding
      the efficacy of DNA vaccination in humans. Here, we present results from a dose
      escalation clinical trial of a dual expression plasmid encoding carcinoembryonic
      antigen (CEA) and hepatitis B surface antigen (HBsAg) in 17 patients with
      metastatic colorectal carcinoma. CEA was selected as a prototypic tumor
      associated self-antigen, and the HBsAg cDNA was included as a positive control
      for immune response to the DNA vaccine without relying upon breaking tolerance to
      a self-antigen. Groups of 3 patients received escalating single i.m. doses of the
      DNA vaccine at 0.1, 0.3, and 1.0 mg. Subsequent groups of 3 patients received
      three repetitive 0.3- or 1.0-mg doses at 3-week intervals. A final group of 2
      patients received three repetitive 2.0 mg doses at 3-week intervals. Toxicity was
      limited to transient grade 1 injection site tenderness, fatigue, and creatine
      kinase elevations, each affecting a minority of patients in a non-dose-related
      manner. Repetitive dosing of the DNA vaccine induced HBsAg antibodies in 6 of 8
      patients, with protective antibody levels achieved in four of these patients. CEA
      specific antibody responses were not observed, but 4 of 17 patients developed
      lymphoproliferative responses to CEA after vaccination. No objective clinical
      responses to the DNA vaccine were observed among this population of patients with
      widely metastatic colorectal carcinoma. Nevertheless, this pilot trial has
      provided encouraging human immune response data in support of this vaccine
      technology.

PMID- 12231518
TI  - Phase I and pharmacokinetic study of the new taxane analog BMS-184476 given
      weekly in patients with advanced malignancies.
AB  - PURPOSE: The study was designed to establish the maximum administered dose and
      maximum tolerated dose (MTD) of BMS-184476, an analogue of paclitaxel, given
      weekly for 3 consecutive weeks every 28 days, later amended to a regimen of
      weekly administration for 2 consecutive weeks every 21 days. EXPERIMENTAL DESIGN:
      Adult patients with solid tumors received BMS-184476 i.v. on days 1, 8, and 15
      without premedication. The trial followed a modified accelerated titration
      design. Doses of 7, 14, 28, 40, 50, and 60 mg/m(2)/wk were investigated.
      Pharmacokinetics of BMS-184476 in plasma and urine were investigated by high
      performance liquid chromatography assay. RESULTS: Fifty-three patients were
      treated; the maximum administered dose was 60 mg/m(2)/wk, and the MTD was 50
      mg/m(2)/wk. Dose-limiting neutropenia was the main toxicity. Neutropenia at the
      higher dose levels frequently prevented administration of the day 15 dose, and a
      modified schedule at MTD dosing on days 1 and 8 every 21 days was evaluated and
      found more feasible for Phase II studies. Diarrhea was the main nonhematological
      toxicity; other toxicities were vomiting, cumulative fatigue, and loss of
      appetite. Two patients died of neutropenia-related complications. Antitumor
      activity was observed in patients with breast and non-small cell lung cancer,
      with confirmed partial responses in 22% of patients. BMS-184476 was the main
      species found in the plasma with <5% present as paclitaxel or sulfoxide
      metabolites. The PKs of BMS-184476 appeared to be linear in the dose range of 7
      60 mg/m(2). CONCLUSION: The recommended dose and schedule of weekly BMS-184476 is
      50 mg/m(2) on days 1 and 8 every 21 days.

PMID- 12231519
TI  - Results of a Phase I dose-escalating study of the antiangiogenic agent, SU5416,
      in patients with advanced malignancies.
AB  - SU5416 is a small molecule antiangiogenic agent that inhibits vascular
      endothelial growth factor (VEGF) stimulation of the KDR tyrosine kinase receptor.
      In this Phase I dose escalation trial, a weekly dose schedule of SU5416 was
      tested whereby an initial 5-day loading dose was followed by weekly maintenance
      infusions. The start dose was 20 mg/m(2) for the loading dose followed by 65
      mg/m(2) for the weekly infusions. Dose escalations occurred at 33% until a final
      dose of 65 mg/m(2) (loading dose) and 190 mg/m(2) (weekly infusion) was obtained.
      Twenty-two patients were treated at five dose levels; tumor types included
      gastrointestinal (8), breast (3), lung (4), sarcoma (2), and other (5). The most
      common serious drug-related toxicity was headache, often associated with nausea
      and vomiting. Grade 1 and 2 toxicities included headache, nausea, vomiting,
      asthenia, pain at the infusion site, phlebitis, change in voice, and fevers. Of
      19 evaluable patients, 4 obtained clinical benefit as defined by tumor regression
      (1) or disease stabilization for at least 12 weeks (3). Pharmacokinetic data
      revealed that the weekly infusion schedule prevented the reported 50-60%
      induction in SU5416 clearance observed with either daily or twice weekly dosing.
      Higher baseline levels of urine VEGF were observed in the 4 patients who gained
      clinical benefit, suggesting this may be a useful marker for predicting response
      to anti-VEGF therapies. Our results suggest that a weekly schedule of SU5416
      shows signs of biological activity and is well tolerated at doses up to 145
      mg/m(2).

PMID- 12231520
TI  - A Phase I study of combined modality (90)Yttrium-CC49 intraperitoneal
      radioimmunotherapy for ovarian cancer.
AB  - PURPOSE: The purpose of this study was to determine the feasibility and maximum
      tolerated dose of (90)Yttrium-CC49 ((90)Y-CC49) as the radioimmunotherapy (RIT)
      component of an i.p. combined modality treatment for recurrent ovarian cancer.
      EXPERIMENTAL DESIGN: A Phase I trial of (90)Y-CC49 RIT was conducted in ovarian
      cancer patients who had persistent or recurrent intra-abdominal disease, had
      failed one or two prior chemotherapy regimens, and demonstrated TAG-72
      expression. Patients were treated with a previously established combined modality
      treatment protocol of s.c. IFN alpha2b, i.p. paclitaxel, and increasing dosages
      of i.p. (90)Y-CC49. Patients were monitored for toxicity, generation of human
      antimouse antibody response, and clinical efficacy. RESULTS: Twenty eligible
      patients were treated per study specifications. All patients had been treated
      with debulking and paclitaxel/carboplatin-based chemotherapy at initial
      diagnosis. The patients included 11 patients with persistent disease at the time
      of second look laparotomy and 9 patients with delayed recurrence. Patients were
      treated with i.p. (90)Y-CC49 given in combination with s.c. IFN alpha2b (dose of
      3 x 10(6) units for a total of four doses) and i.p. paclitaxel (dose of 100
      mg/m(2)). RIT treatment was associated with primarily hematological toxicity. The
      maximum tolerated dose of i.p. (90)Y-CC49 was established at 24.2 mCi/m(2) in
      this combined regimen. Of nine patients with measurable disease, two had partial
      responses lasting 2 and 4 months. Of 11 patients with nonmeasurable disease,
      median time to progression was 6 months in 7 patients who recurred; 4 of these
      patients remain no evidence of disease at 9+, 18+, 19+, and 23+ months.
      CONCLUSIONS: (90)Yttrium-CC49-based RIT in combination with IFN alpha2b and i.p.
      paclitaxel is feasible and well tolerated at a dose of < or =24.2 mCi/m(2).

PMID- 12231521
TI  - Postremission therapy with low-dose interleukin 2 with or without intermediate
      pulse dose interleukin 2 therapy is well tolerated in elderly patients with acute
      myeloid leukemia: Cancer and Leukemia Group B study 9420.
AB  - PURPOSE: The purpose of the study is to investigate the tolerability of
      interleukin 2 (IL-2) after intensive chemotherapy in elderly acute myeloid
      leukemia (AML) patients in first complete remission (CR). EXPERIMENTAL DESIGN:
      AML patients > or =60 years in CR after induction and consolidation chemotherapy
      on Cancer and Leukemia Group B study 9420 were eligible if they had neutrophils >
      or =1 x 10(9)/liters and platelets > or =75 x 10(9)/liters. Patients received low
      dose IL-2 (1 x 10(6) IU/m(2)/day s.c. for 90 days) or low-dose IL-2 with
      intermediate pulse doses (6-12 x 10(6) IU/m(2)/day s.c. for 3 days) every 14 days
      (maximum five pulses). In a subset of patients, we investigated the expression of
      NKG2D ligands by leukemic cells because they are likely important mediators of
      natural killer cytotoxicity. RESULTS: Of 35 CR patients receiving IL-2, 34 were
      evaluable for toxicity. Median age was 67 (range, 60-76) years. Thirteen of 16
      patients receiving low-dose IL-2 completed the planned therapy, and 11 of 18 who
      also received intermediate pulse dose IL-2 therapy completed all five pulses. The
      spectrum of toxicity in both groups was similar, with predominantly grade 1-2
      fatigue, fever, injection site reactions, nausea, anemia, and thrombocytopenia.
      Grade 3-4 hematological and nonhematological toxicity were more frequent in
      patients also receiving intermediate pulse dose IL-2 therapy. Grade 3-4 fatigue
      and hematological toxicity, although uncommon, were the major causes for
      discontinuing or attenuating therapy. In 8 cases, mRNA for one or more NKG2D
      ligands was detected in leukemic cells obtained at diagnosis before treatment.
      CONCLUSIONS: Low-dose IL-2, with or without intermediate pulse dose therapy,
      given immediately after chemotherapy in first CR to elderly AML patients is well
      tolerated. Expression of NKG2D ligands by leukemic cells was detected in the
      majority of cases tested and should be assessed for correlation with response to
      IL-2 in future studies.

PMID- 12231522
TI  - Phase I trial of 1alpha-hydroxyvitamin d(2) in patients with hormone refractory
      prostate cancer.
AB  - This Phase I study of 1alpha-hydroxyvitamin D(2), an p.o. administered vitamin D
      analogue, in patients with advanced hormone-refractory prostate cancer was
      designed to assess the toxicity, pharmacokinetic and biological markers of drug
      activity, and lastly tumor response data to recommend a dose for Phase II
      studies. 1alpha-Hydroxyvitamin D(2) was administered daily at doses ranging from
      5 to 15 microg/day. Patients were monitored for toxicity and tumor response, and
      blood and urine samples were collected for pharmacokinetics (1alpha,25
      dihydroxyvitamin D(2) levels) and other parameters of biological activity (bone
      markers, parathyroid hormone, urine calcium, and serum phosphorus levels). Twenty
      five patients were enrolled. Main toxicities were hypercalcemia with associated
      renal insufficiency. No other significant toxicity was seen. Pharmacokinetics
      showed an increase in the active metabolite 1alpha,25-dihydroxyvitamin D(2) that
      reached a plateau by week 4 despite continuous drug dosing. Elevation in daily
      urinary calcium excretion and serum phosphorus levels was seen, whereas a
      decrease in serum parathyroid hormone was evident. Two patients showed evidence
      of a partial response, whereas 5 others achieved disease stabilization for > or
      =6 months. 1alpha-Hydroxyvitamin D(2) was well tolerated with main toxicities
      being hypercalcemia and renal insufficiency. All of the toxicity was reversible
      with drug discontinuation. Evidence for drug activity was seen in surrogate
      markers, and pharmacokinetic analysis showed substantial increases in vitamin D
      metabolite levels among the various cohorts. Whereas the defined maximum
      tolerated dose was not reached, the recommended Phase II dose was 12.5 microg/day
      given continuously.

PMID- 12231523
TI  - Phase I clinical trials of tezacitabine [(E)-2'-deoxy-2'
      (fluoromethylene)cytidine] in patients with refractory solid tumors.
AB  - PURPOSE: To evaluate safety, tolerability, and pharmacokinetics of a new
      nucleoside analogue, tezacitabine [(E)-2'-deoxy-2'-(fluoromethylene)cytidine
      (FMdC)] in patients with refractory solid tumors. EXPERIMENTAL DESIGN: Seventy
      patients were enrolled in four separate Phase I trials. Patients had metastatic
      or relapsed cancer of the colon, breast, pancreas, gastrointestinal tract, lung,
      and other sites. FMdC was administered by i.v. infusion over 30 min in one of
      four dose schedules--from once every 3 weeks to twice a week for 3 weeks, with
      dose escalation in each. Maximum doses ranged from 630 to 16 mg/m(2). RESULTS:
      Myelotoxicity, especially neutropenia, was the dominant toxicity and was
      generally dose-related. Grade 3 or 4 neutropenia occurred in 53% of patients but
      was of relatively short duration (1-8 days) in all of the patients. One patient
      experienced grade 3 thrombocytopenia and one patient grade 4 (duration 15 and 11
      days, respectively). Transient febrile episodes were reported in 82% of patients
      with drug administration but were easily controlled. Drug-related
      gastrointestinal events were mild and appeared unrelated to dose.
      Pharmacokinetics were linear with dose, not appreciably affected by schedules,
      and not different after single or multiple doses. Terminal half-life was 3-4 h,
      and 23% of the administered drug was recovered in the urine as unchanged drug.
      The uridine analogue (FMdU), the deaminated metabolite of FMdC, was the primary
      metabolite. Objective antitumor activity was observed in eight patients: one
      exhibited a partial response and seven exhibited stable disease. CONCLUSIONS: In
      general, FMdC was well tolerated. On the basis of the time to recovery from
      neutropenia, the recommended schedule for Phase II studies is one treatment every
      2 weeks, at a minimum dose of 270 mg/m(2).

PMID- 12231525
TI  - A Phase I study of CHS 828 in patients with solid tumor malignancy.
AB  - CHS 828 is a cyanoguanidine, which has demonstrated potent antitumor activity in
      preclinical tumor models. The activity of CHS 828 in vitro showed only low to
      moderate correlation to other antineoplastic agents suggesting a unique mechanism
      of action. Ten females and 6 males (median age 58 years) with solid tumors
      refractory to standard therapy were included in this Phase I study. The study
      drug was administered to fasting patients as a single oral dose on days 1-5 of
      each treatment cycle. Patients received one to six cycles of treatment. The doses
      ranged from 30 mg to 200 mg (total dose within a cycle). Hematological toxicity
      was generally mild and dominated by transient thrombocytopenia and
      lymphocytopenia. Nonhematological toxicity most frequently consisted of nausea,
      vomiting, diarrhea, fatigue, and localized genital mucositis. The dose-limiting
      toxicities were thrombocytopenia, thrombosis, esophagitis, diarrhea, and
      constipation. The recommended Phase II dose of CHS 828 was 20 mg once daily for 5
      days in cycles of 28 days duration. The extent of systemic exposure of CHS 828
      across patients was approximately dose proportional. The time at which the
      highest drug concentration occurs was 2.2 +/- 1.3 h and half-life was 2.1 +/-
      0.52 h (mean +/- SD). Large intra- and interindividual variation in dose level
      adjusted maximum plasma concentration and the area under the curve from time 0 h
      to infinity were observed. There was an apparent inverse relationship between
      systemic exposure of CHS 828, and thrombocyte and lymphocyte nadir levels. No
      objective tumor responses were observed, and 7 patients showed stable disease
      after two courses of therapy.

PMID- 12231524
TI  - Phase II clinical trial of N-(4-Hydroxyphenyl)retinamide and tamoxifen
      administration before definitive surgery for breast neoplasia.
AB  - PURPOSE: Surrogate end point biomarkers (SEBs) that can be measured in ductal
      carcinoma in situ or early-stage invasive cancer are needed to improve the
      efficiency and reduce the cost of chemoprevention trials. EXPERIMENTAL DESIGN: We
      conducted a prospective study to develop SEBs for tamoxifen and N-[4
      hydroxyphenyl]retinamide by administering either a placebo or both drugs for 2-4
      weeks to women with ductal carcinoma in situ or early invasive cancers in the
      interval between the initial diagnostic core biopsy and definitive surgery. The
      major statistical end point of the study was pre- versus posttreatment change in
      cell proliferation, as measured by changes in Ki67 labeling indices. In addition,
      estrogen receptor (ER), HER2/neu, p53, retinoid receptors, and DNA index were
      measured. RESULTS: Between February 1997 and April 200, 52 patients were
      registered on the study, and 36 (20 in the placebo arm and 16 in the treatment
      arm) were available for analysis. No statistically significant pre- versus
      posttreatment differences in Ki67 labeling index or in the other markers were
      observed in the treatment arm compared with the placebo arm. There was a trend
      toward increased treatment response in ER-positive versus ER-negative patients,
      but this could not be rigorously analyzed because of the low sample size and the
      unequal distribution of ER-positive patients in the two study arms. CONCLUSION:
      Future SEB trials for breast carcinoma must (a) incorporate information about
      patient hormonal status into the study design and (b) resolve problems in patient
      accrual.

PMID- 12231526
TI  - Identification of a novel HLA-A*0201-restricted, cytotoxic T lymphocyte epitope
      in a human glioma-associated antigen, interleukin 13 receptor alpha2 chain.
AB  - PURPOSE: Interleukin 13 receptor alpha2-chain (IL-13Ralpha2) has been reported to
      be abundantly and specifically overexpressed in glioblastoma multiforme. Here we
      report the identification of a CTL epitope derived from the IL-13Ralpha2.
      EXPERIMENTAL DESIGN: Mature dendritic cells (DCs) were pulsed with each of the
      synthetic peptides that were designed, based on a binding affinity-based
      prediction and a proteosomal cleavage site prediction system, and used to
      stimulate autologous CD8+ T cells from an HLA-A2+ healthy donor. After four to
      six cycles of restimulation, the immunoreactivity of the T cells was analyzed for
      specific IFN-gamma production and CTL reactivity. RESULTS: Of the five peptides
      tested, IL-13Ralpha(345-354) (WLPFGFILI) induced a CD8(+) T-cell line that
      specifically produced IFN-gamma in response to HLA-A2+ T2 cells pulsed with the
      relevant peptide and lysed these cells. Peptide titration assays demonstrated
      that half-maximal lysis of IL-13Ralpha(345-354) peptide-reactive CD8(+) T cells
      required peptide loading concentration of approximately 5 nM. Perhaps most
      importantly, this CD8(+) T-cell line also displayed lytic activity against the
      HLA-A2+ human glioma cell lines that express IL-13Ralpha2. CONCLUSIONS: This
      novel CTL epitope may therefore serve as an attractive component of peptide-based
      vaccines to treat glioma and as a surrogate marker of T-cell immune responses in
      patients before and after therapy.

PMID- 12231527
TI  - Vascular endothelial growth factor secretion is an independent prognostic factor
      for relapse-free survival in pediatric acute myeloid leukemia patients.
AB  - Substantial improvements in long-term survival have been made with acute myeloid
      leukemia (AML). However, the overall success rate in treatment of AML is around
      50%, despite intensive chemotherapeutic regimens. AML cell survival seems to be
      related to vascular endothelial growth factor (VEGF). The purpose of this study
      was to investigate whether VEGF production by AML cells is a prognostic factor
      for therapeutic outcome and whether this is independent of known prognostic
      factors such as WBC count, French-American-British (FAB) classification, and risk
      assessment in which the presence of t(8;21), t(15;17), and inv(16) or FAB M3
      defines a low-risk group. Pretreatment levels were measured in the supernatant of
      AML cells obtained from 47 children with newly diagnosed AML treated between 1988
      and 1998. All patients were treated with intensive chemotherapeutic protocols
      from the Dutch Childhood Leukemia Study Group [DCLSG (DCLSG-ANLL87, DCLSG
      ANLL92/94, and DCLSG-ANLL97)]. VEGF was measured at the mRNA level with reverse
      transcription-PCR and at the protein level using a VEGF immunoassay. VEGF in the
      supernatant from AML cells was highly variable and in concordance with reverse
      transcription-PCR results. The low-risk group had significantly lower VEGF levels
      compared with all others (P = 0.002). VEGF levels were significantly increased in
      AML FAB M4/M5 versus AML patients with FAB M1/M2/M3/M4eo (P = 0.011), who are
      reported to have a longer remission duration. Subsequently, the influence of
      different variables on therapeutic outcome was analyzed. No differences were
      found in overall survival. But within the limits of the small patient population,
      VEGF levels as well as age at diagnosis had an independent significant effect on
      relapse-free survival (P = 0.032 and P = 0.029, respectively) in multivariate
      analysis.

PMID- 12231528
TI  - Effect of anal epidermoid cancer-related viruses on the dendritic (Langerhans')
      cells of the human anal mucosa.
AB  - PURPOSE: The incidence of anal cancer is high in patients with anal condyloma.
      HIV increases this risk. We analyzed anal mucosa from normal individuals and
      individuals with condyloma. EXPERIMENTAL DESIGN: Normal anal mucosa from 155
      consecutively recruited patients (102 HIV-positive and 53 HIV-negative) with anal
      condyloma was compared with that obtained from 30 HIV-negative patients after
      hemorrhoid surgery (controls). Langerhans' cells (LCs), T lymphocytes, and
      viruses [EBV, cytomegalovirus, herpes simplex virus 1, and human papillomavirus
      (HPV) types] in anal mucosa and HIV load and CD4 T-lymphocyte counts in the serum
      were characterized. RESULTS: None of the control individuals had anal squamous
      intraepithelial lesion or HPV versus 19 HIV-positive and 4 HIV-negative patients
      with anal condyloma (P = 0.07). The number of LCs/mm in anal tissue was
      significantly higher in HIV-negative patients with condylomata (median, 30;
      range, 2-130) than in HIV-positive patients (median, 15; range, 0-100) or in
      controls (median, 17; range, 4-35). In HIV-negative individuals, the occurrence
      of condylomata was linked with a higher number of LCs. Significant differences
      were observed between HIV-positive and HIV-negative patients with anal
      condylomata:number of LCs/mm anal tissue, oncogenic HPV (26% versus 8%), other
      current infections (35.6% versus 5%), being male (93% versus 74%). Multivariate
      regression analysis found HIV as the only risk factor for a decrease in the
      number of LCs (odds ratio, 6; 95% confidence interval, 2.28-16.1; P < 0.001) and
      the serum HIV load (odds ratio, 4.9; 95% confidence interval, 1.1-21.4 log/ml; P
      < 0.03) but not the serum CD4 T-lymphocyte rate as a predictive risk factor for
      having <17 LCs/mm tissue. CONCLUSION: HPV increases the number of LCs in anal
      mucosa in HIV-negative individuals. HIV alters anal dendritic cells, likely
      leading to an increase in anal cancer risk.

PMID- 12231529
TI  - Expansion of microsatellite in the thyroid hormone receptor-alpha1 gene linked to
      increased receptor expression and less aggressive thyroid cancer.
AB  - PURPOSE: The purpose of this study was to determine whether the length of the
      THRA1 microsatellite, which resides in a noncoding portion of the thyroid hormone
      receptor-alpha1 gene, affects receptor expression and is linked to
      clinicopathological parameters in thyroid cancer. EXPERIMENTAL DESIGN: In 30
      cases of surgically resected sporadic thyroid cancer, the length of the THRA1
      microsatellite was determined by DNA sequence analysis, and expression of thyroid
      hormone receptor-alpha1 was assessed immunohistochemically in thin sections cut
      from tumor blocks. The length of THRA1 and expression of thyroid hormone receptor
      alpha1 were also assessed in seven cancer cell lines. Regression analysis was
      used to gauge the correlation between the size of THRA1 and receptor expression.
      Multivariate analysis was used to test for links to the clinical parameters of
      gender, age, histology, stage, nodal involvement, distant metastasis,
      extrathyroidal invasion and tumor-node-metastasis (TNM) classification. RESULTS:
      A statistically significant correlation between the length of THRA1 and thyroid
      hormone receptor-alpha1 expression was observed in both cell lines and primary
      thyroid cancers. Thyroid tumors that displayed higher than average thyroid
      hormone receptor-alpha1 expression had expanded THRA1 microsatellites and were
      less aggressive as judged by TNM ranking. A statistically significant correlation
      was also found between low thyroid hormone receptor-alpha1 expression and more
      aggressive thyroid cancer, as judged by extrathyroidal invasion and nodal
      involvement. CONCLUSIONS: Less aggressive thyroid cancer was found to be linked
      to increased thyroid hormone receptor-alpha1 expression and an expanded THRA1
      microsatellite.

PMID- 12231530
TI  - Detection of mitochondrial DNA alterations in the serum of hepatocellular
      carcinoma patients.
AB  - PURPOSE: Somatic mutations in mitochondrial DNA (mtDNA) have recently been
      detected in various cancers. These mutations could possibly be detected in serum
      because mtDNA has a higher copy number than nuclear DNA. Thus, we examined
      genetic alterations in the D-loop region of mtDNA in hepatocellular carcinoma
      (HCC) patients. EXPERIMENTAL DESIGN: Fifty patients with HCC were investigated in
      this study. Somatic mutations in the D-loop region of tumor mtDNA were screened
      by direct sequencing, and then the paired serum samples were investigated using
      mutation-specific mismatch ligation assay. RESULTS: Fifteen of 100 sequence
      variants that were detected in tumor mtDNA have not been recorded previously.
      True somatic mutations in the D-loop region were detected in 17 of 50 patients
      (34%). Subsequent screening for paired serum by mismatch ligation assay revealed
      that 5 of 15 paired serum samples (33%) contained the same mutations as primary
      tumors. CONCLUSIONS: mtDNA mutation may be a novel tumor marker of HCC and may
      prove effective for detection of tumor DNA in the serum.

PMID- 12231531
TI  - Molecular detection of circulating esophageal squamous cell cancer cells in the
      peripheral blood.
AB  - PURPOSE AND EXPERIMENTAL DESIGN: To detect surgically resectable tumors earlier
      and improve the prognosis of esophageal squamous cell carcinoma patients, we
      examined deltaNp63 expression that was specific for squamous cell carcinoma in
      blood samples obtained from 43 esophageal cancer patients. RESULTS: Seventeen of
      33 (52%) patients with primary esophageal squamous cell carcinoma and 6 of 10
      (60%) patients with postoperative recurrent squamous cell carcinoma had
      detectable deltaNp63 expression in their peripheral blood using deltaNp63
      specific reverse transcription-PCR. Furthermore, deltaNp63 is a more sensitive
      marker compared with other commonly used tumor markers such as squamous cell
      carcinoma-associated antigen and carcinoembryonic antigen. CONCLUSIONS: This
      approach would be potentially useful for the monitoring of patients with this
      aggressive disease.

PMID- 12231532
TI  - hTERT expression is a prognostic factor of survival in patients with stage I non
      small cell lung cancer.
AB  - Activation of telomerase plays a critical role in unlimited proliferation and
      immortalization of cells. The purpose of this study was to evaluate the
      significance of human telomerase reverse transcriptase catalytic subunit (hTERT)
      as a prognostic marker. The expression of hTERT in a large population of 153
      patients with stage I non-small cell lung cancer was analyzed using the in situ
      hybridization technique. We found that diffuse and clear hTERT expression was
      present in 51 (33%) of 153 patients. Kaplan-Meier analysis showed that hTERT
      expression was associated with shorter overall survival (P = 0.04), shorter
      disease-specific survival (P = 0.03), and shorter disease-free survival (P =
      0.02). Multivariate analysis confirmed this independent prognostic value of hTERT
      expression. Our results indicated that hTERT mRNA expression is associated with
      malignant tumor progression and poor outcome. hTERT may serve as a useful marker
      to identify patients with poor prognosis and to select patients with early-stage
      non-small cell lung cancer who might benefit from adjuvant treatment.

PMID- 12231533
TI  - Two-hit inactivation of FHIT by loss of heterozygosity and hypermethylation in
      breast cancer.
AB  - PURPOSE: The FHIT gene, which spans the FRA3B fragile site at chromosome 3p14.2,
      is a candidate tumor suppressor gene in breast carcinomas. In this study, we
      would like to delineate more precisely its role in breast tumorigenesis.
      EXPERIMENTAL DESIGN: To confirm the tumorigenic role of FHIT, 46 sporadic
      invasive ductal carcinomas of the breast were tested for the "two hits" required
      to inactivate this gene. Microsatellite loss of heterozygosity (LOH) was
      considered as the first hit. To examine the possibility that hypermethylation
      serves as the second hit for FHIT inactivation, methylation of 5'-CpG islands of
      FHIT was analyzed by methylation-specific PCR. RESULTS: LOH was detected in 8 of
      40 informative tumors, and hypermethylation was observed in 22 of 46 (48%) cases.
      Aberrant FHIT protein expression was found in 31 of 46 (67%) cases examined. All
      seven tumors showing both LOH and hypermethylation showed complete loss of Fhit
      protein expression. In addition, a significant positive association was found
      between the existence of LOH and 5'-CpG island hypermethylation (P = 0.04), which
      was consistent with the two-hit model. CONCLUSIONS: To our knowledge, this study
      provides the first evidence that biallelic inactivation of FHIT by LOH and
      hypermethylation leads to the complete inactivation of FHIT gene in patients with
      breast cancer. Silencing of the FHIT gene by promoter hypermethylation occurs in
      primary breast carcinomas, especially those with LOH. These findings support a
      role for this tumor suppressor gene in sporadic breast tumorigenesis.

PMID- 12231534
TI  - Active matrix metalloproteinase 9 expression is associated with primary
      glioblastoma subtype.
AB  - PURPOSE: Glioblastoma multiforme (GBM) is an aggressive cancer characterized by
      extensive brain invasion. Matrix metalloproteinase (MMP)-9 plays a major role in
      this process. GBMs can be divided into two subtypes based on distinct clinical
      and molecular features. Primary GBMs arise de novo and frequently overexpress the
      epidermal growth factor receptor (EGFR) and its ligand-independent variant, EGFR
      variant III (EGFRvIII); secondary GBMs progress from a lower grade glioma and
      commonly harbor p53 mutations. Because EGFR signaling promotes MMP-9 expression
      and activation in other cancer cell types, we analyzed whether MMP-9 was
      associated with primary GBM subtype. EXPERIMENTAL DESIGN: Autopsies were
      performed on 20 GBM patients, and MMP expression was assessed by gelatin
      zymography in the tumor and the adjacent normal brain. EGFR, EGFRvIII, p53, and
      activated mitogen-activated protein kinase/extracellular signal-regulated kinase
      were assessed by immunohistochemistry, and associations between molecular
      phenotype and MMP-9 expression were analyzed. RESULTS: Latent MMP-9 was detected
      in 90% of tumors, and active MMP-9 was found in 50% of tumors. MMP-9 was not
      detected in any of the normal brain samples (P < 0.001). More importantly,
      primary GBMs were significantly more likely than secondary GBMs to contain active
      MMP-9 (69% of primary and 14% of secondary GBMs contained active MMP-9; P =
      0.027). Active MMP-9 was observed in 73% of EGFR-overexpressing/wild-type p53
      staining tumors but in only 20% of EGFR-negative/aberrant p53-staining tumors (P
      = 0.072). Active MMP-9 expression was even more strongly correlated with EGFRvIII
      expression, occurring in 83% of the EGFRvIII-immunopositive tumors but in none of
      the EGFRvIII-negative tumors (P = 0.0004). Extracellular signal-regulated kinase
      activation was also strongly correlated with EGFRvIII expression (P < 0.0001) and
      with MMP-9 activation (P = 0.003). CONCLUSIONS: These results identify a novel
      association between MMP-9 activation and primary GBM subtype and suggest that
      primary GBM patients, especially those whose tumors express EGFRvIII, may benefit
      from anti-MMP therapy.

PMID- 12231535
TI  - Identification of cyclin D1 mRNA overexpression in B-cell neoplasias by real-time
      reverse transcription-PCR of microdissected paraffin sections.
AB  - PURPOSE: Overexpression of cyclin D1 mRNA and protein as a result of the
      chromosomal translocation t(11;14)(q13;q32) is a highly specific molecular marker
      of mantle cell lymphoma, but cyclin D1 dysregulation can also be found in other B
      cell neoplasias. The aim of the study was to develop a precise and reliable tool
      for quantitation of cyclin D1 mRNA suitable for archival clinical specimens.
      EXPERIMENTAL DESIGN: A real-time reverse transcription-PCR (RT-PCR) assay was
      used to quantitate cyclin D1 mRNA copy numbers. Using 2000 microdissected cells
      as template, 104 formalin-fixed, paraffin-embedded lymph node, spleen, and
      decalcified bone marrow biopsies from a panel of 95 cases of B-cell non-Hodgkin's
      lymphomas (B-NHLs) were analyzed. In addition, cyclin D1 protein expression was
      assessed by immunohistochemistry. RESULTS: Strong cyclin D1 mRNA overexpression
      was detected in mantle cell lymphomas (23 of 23), hairy cell leukemias (5 of 19),
      and multiple myelomas (7 of 23) with particularly high levels in 2 of the latter
      cases. Intermediate transcript levels were found in 5 of 23 multiple myelomas and
      7 of 19 hairy cell leukemias. B-cell chronic lymphocytic leukemias (10 of 10),
      follicular lymphomas (9 of 9), mucosa-associated lymphoid tissue lymphomas (5 of
      5) and reactive lymphoid tissues with the exception of normal spleen had no or
      very low cyclin D1 expression. In comparison with real-time RT-PCR,
      immunohistochemistry showed a lower level of sensitivity, more variability, and
      did not allow accurate quantitation. CONCLUSIONS: Real-time RT-PCR for cyclin D1
      mRNA is an excellent tool for the differential diagnosis of B-NHLs and, in
      combination with microdissection, a powerful approach for retrospective trials
      using archival clinical specimens as tissue source. Furthermore, real-time RT-PCR
      may help to identify subgroups of B-NHLs according to cyclin D1 mRNA copy numbers
      and to investigate the possible influence of different chromosomal breakpoints on
      cyclin D1 expression.

PMID- 12231536
TI  - Reactive stroma in human prostate cancer: induction of myofibroblast phenotype
      and extracellular matrix remodeling.
AB  - PURPOSE: Generation of a reactive stroma environment occurs in many human cancers
      and is likely to promote tumorigenesis. However, reactive stroma in human
      prostate cancer has not been defined. We examined stromal cell phenotype and
      expression of extracellular matrix components in an effort to define the reactive
      stroma environment and to determine its ontogeny during prostate cancer
      progression. EXPERIMENTAL DESIGN: Normal prostate, prostatic intraepithelial
      neoplasia (PIN), and prostate cancer were examined by immunohistochemistry.
      Tissue samples included radical prostatectomy specimens, frozen biopsy specimens,
      and a prostate cancer tissue microarray. A human prostate stromal cell line was
      used to determine whether transforming growth factor beta1 (TGF-beta1) regulates
      reactive stroma. RESULTS: Compared with normal prostate tissue, reactive stroma
      in Gleason 3 prostate cancer showed increased vimentin staining and decreased
      calponin staining (P < 0.001). Double-label immunohistochemistry revealed that
      reactive stromal cells were vimentin and smooth muscle alpha-actin positive,
      indicating the myofibroblast phenotype. In addition, reactive stroma cells
      exhibited elevated collagen I synthesis and expression of tenascin and fibroblast
      activation protein. Increased vimentin expression and collagen I synthesis were
      first observed in activated periacinar fibroblasts adjacent to PIN. Similar to
      previous observations in prostate cancer, TGF-beta1-staining intensity was
      elevated in PIN. In vitro, TGF-beta1 stimulated human prostatic fibroblasts to
      switch to the myofibroblast phenotype and to express tenascin. CONCLUSIONS: The
      stromal microenvironment in human prostate cancer is altered compared with normal
      stroma and exhibits features of a wound repair stroma. Reactive stroma is
      composed of myofibroblasts and fibroblasts stimulated to express extracellular
      matrix components. Reactive stroma appears to be initiated during PIN and evolve
      with cancer progression to effectively displace the normal fibromuscular stroma.
      These studies and others suggest that TGF-beta1 is a candidate regulator of
      reactive stroma during prostate cancer progression.

PMID- 12231537
TI  - The paradoxical expression of maspin in ovarian carcinoma.
AB  - Maspin is a noninhibitory member of the serpin family that is down-regulated in
      breast carcinoma but overexpressed in pancreatic carcinoma. There are no
      published data regarding the role of maspin in ovarian carcinoma, which is the
      focus of the present study. Ovarian cell lines (normal and cancer) and tumors (80
      invasive, 14 benign, and 10 low malignant potential) were evaluated for maspin
      expression and localization. Normal ovarian surface epithelial cells had low
      levels of maspin. Two of four ovarian cancer cell lines (OVCAR3 and SKOV3)
      expressed maspin, whereas the cell line EG had weak expression, and 222 had no
      detectable maspin. Subcellular fractionation studies revealed that the two maspin
      positive ovarian cancer cell lines contained maspin in both the nuclear and
      cytosolic compartments. Wild-type maspin was transfected into the aggressive
      ovarian cancer cell lines SKOV3 and 222. The in vitro invasive activity of the
      maspin-transfected cell lines was 44-68% lower than respective controls. The
      histopathology analysis revealed that among the ovarian tumors examined, 57 (71%)
      were ranked positive for maspin. Thirty (37%) of the invasive tumors
      overexpressed maspin. Invasive cancers were more likely to have predominantly
      cytoplasmic staining compared with benign and low-malignant-potential tumors.
      Maspin overexpression was significantly associated with a high tumor grade (P =
      0.004), the presence of ascites (P = 0.02), a lower likelihood of optimal
      surgical cytoreduction (P = 0.04), and a shorter duration of overall survival
      (median survival, 6.33 versus 2.67 years; P = 0.003). The Cox proportional
      hazards multivariate model revealed that maspin overexpression and high stage
      were independent predictors of survival. Thus, maspin was found to be
      overexpressed in a substantial proportion of ovarian tumors, which may serve as
      an adverse prognostic factor; however, its localization may provide new clues as
      to its activity and function. These paradoxical results may offer new insights
      regarding the role of maspin in ovarian cancer progression that may also impact
      diagnosis and treatment strategies.

PMID- 12231539
TI  - Absence of ST7 gene alterations in human cancer.
AB  - The ST7 gene was cloned and mapped to chromosome 7q31.1-q31.2, a region suspected
      of containing a tumor suppressor gene involved in a variety of human cancers.
      Subsequent investigation described the presence of ST7 mutations in human cell
      lines derived from breast tumors and primary colon carcinoma. Introduction of the
      ST7 cDNA into a prostate cancer-derived cell line abrogated in vivo
      tumorigenecity in nude mice. To clarify the role of the ST7 gene in cancer, we
      scrutinized primary head and neck squamous cell carcinomas, invasive ductal
      carcinomas of the breast, and adenocarcinomas of the colon. Loss of
      heterozygosity of D7S522/D7S677 was detected in 24% (4 of 17) of head and neck
      squamous cell carcinomas, 17% (2 of 12) of invasive ductal carcinomas of the
      breast, and 33% (8 of 24) of adenocarcinomas of the colon, but no somatic
      mutations were found in any of these specimens. We then searched for mutations in
      breast cancer cell lines and found a complete wild-type sequence in all,
      including cell lines previously reported to harbor mutations. We believe that the
      ST7 gene is not a primary target of inactivation in most human cancers with loss
      of heterozygosity at 7q31.1-q31.2.

PMID- 12231538
TI  - Increased levels of tissue endostatin in human malignant gliomas.
AB  - PURPOSE: Malignant gliomas are typically angiogenic and express greater amounts
      of angiogenic factors. We examined glioma tissues for their expression of an
      endogenous inhibitor of angiogenesis, endostatin, a COOH-terminal fragment of
      collagen XVIII. EXPERIMENTAL DESIGN: We examined frozen tissues from 51 patients
      with astrocytic tumors (grade 2, 13; grade 3, 9; and grade 4, 29). Frozen tissues
      were subjected to immunoblot analysis and immunohistochemistry for endostatin.
      Tumor vascular density was determined by calculating the percentage of tumor
      capillary vessel areas/tissue section area. Tissue concentrations of vascular
      endothelial growth factor and basic fibroblast growth factor were examined by
      enzyme immunoassay. RESULTS: The levels of endostatin protein estimated by
      immunoblotting were significantly higher in grade 4 than lower-grade glioma
      tissues. The immunoreactive bands for endostatin were identified as the fragment
      derived from noncollagenous domain 1 of collagen XVIII, a peptide 15 residues
      longer than endostatin toward the NH(2)-terminal end, by NH(2)-terminal amino
      acid sequencing. In addition to an intense immunoreactivity for endostatin in
      tumor blood vessels, sections from malignant gliomas showed widely distributed
      immunoreactivity around tumor cells near the hyperplastic microvessels. The tumor
      vascular density and the levels of vascular endothelial growth factor in grade 4
      glioma tissues were significantly higher than grade 2 and grade 3 gliomas,
      whereas the levels of basic fibroblast growth factor were the same. CONCLUSIONS:
      The results indicate a positive correlation between the levels of tissue
      endostatin and malignancy grades in gliomas. The endostatin may be released near
      the tumor blood vessels with hyperplasia to counteract angiogenic stimuli in
      malignant gliomas.

PMID- 12231540
TI  - Tumor-infiltrating macrophages are involved in suppressing growth and metastasis
      of human prostate cancer cells by INF-beta gene therapy in nude mice.
AB  - PURPOSE: This study was to determine the role of tumor-infiltrating macrophages
      in IFN-beta-induced host defense against prostate cancer. EXPERIMENTAL DESIGN:
      Efficacy of adenovirus-mediated IFN-beta gene therapy against orthotopic
      xenografts of human prostate cancer was tested in macrophage-compromised nude
      mice. Immunohistochemistry and Northern blotting were used to elucidate
      mechanisms responsible for the IFN-beta gene therapy. RESULTS: PC-3MM2 human
      prostate cancer cells were inoculated into the prostates of nude mice.
      Intralesional injection of an adenoviral vector-encoding murine IFN-beta (AdmIFN
      beta) but not control vector AdE/1 suppressed growth of PC-3MM2 tumors in a dose
      dependent manner, with a maximal reduction of tumor weight by approximately 85%
      at 2 x 10(9) plaque-forming units. The therapy prevented metastasis, eradicated
      established metastases in some mice, and prolonged the survival of tumor-bearing
      mice. The efficacy of AdmIFN-beta therapy was reduced significantly in mice
      treated with macrophage-selective anti-Mac-1 and anti-Mac-2 antibodies. Moreover,
      the i.p. injection of the antibodies restored the tumorigenicity of PC-3MM2 cells
      stably engineered with murine IFN-beta gene. Tumor-infiltrating macrophages,
      significantly increased in AdmIFN-beta-injected lesions, were depleted by the
      antibodies. The therapy stimulated expression of the inducible nitric oxide
      synthase, down-regulated transforming growth factor-beta1 and interleukin-8,
      reduced microvessel density, and resulted in apoptosis of endothelial cells in
      the lesions. These effects of AdmIFN-beta were partially diminished in mice
      treated with the antibodies. CONCLUSIONS: These data suggest that macrophages
      play an important role in IFN-beta gene therapy and that intralesional delivery
      of the IFN-beta gene could be an effective therapy for clinically localized human
      prostate cancer.

PMID- 12231541
TI  - Rat and human liver cytochrome P-450 isoform metabolism of ecteinascidin 743 does
      not predict gender-dependent toxicity in humans.
AB  - Ecteinascidin 743 (ET743, NSC648766) is a marine natural product with potent in
      vivo activity in human xenograft models. Hepatotoxicity was the most prominent
      toxicity in preclinical studies and was greater in female rats than in male rats.
      To assess the potential implications for human toxicities, the in vitro
      metabolism of ET743 was characterized using rat and human preparations. NADPH
      dependent ET743 metabolism was greater with male rat liver microsomal
      preparations than with preparations from female rats and was induced by
      pretreatment of rats with phenobarbital and dexamethasone but not by pretreatment
      with 3-methylcholanthrene. Rat and human microsomal metabolism of ET743 was
      reduced in the presence of chemical CYP3A inhibitors or antirat CYP3A2 antiserum
      and to a much lesser extent by CYP2E, CYP2C, and CYP2A inhibitors. In human liver
      panel studies, ET743 disappearance was highly correlated with CYP3A activities
      and to a lesser extent with CYP2C activities. ET743 was metabolized by a number
      of cDNA-expressed rat P-450 isoforms, including male-predominant CYP2A2 and
      CYP3A2. ET743 was metabolized by cDNA-expressed human CYP3A4 and to a much lesser
      extent by CYP2C9, CYP2D6, and CYP2E1 preparations. Three oxidative metabolites
      were detected in cDNA-expressed isoform incubations, including the N-demethylated
      metabolite ET729 and two additional products characterized by laser capture-mass
      spectrometry analyses. The plasma pharmacokinetics and biliary excretion of ET743
      were characterized in rats. There were no gender-dependent differences in half
      life or total body clearance values. Although very modest, the biliary excretion
      of ET743 in male rats (0.48%) was greater than in female rats (0.28%). In
      contrast, the biliary excretion of the cytotoxic N-demethylated metabolite ET729
      was 5-fold greater in the female rat (1.05% of dose) than in the male rat (0.19%
      of dose). Biliary excretion of ET729 may contribute to the hepatic toxicity in
      rats. These data are consistent with a major role for CYP3A isoforms in ET743 rat
      and human metabolism. Although there are conflicting data in the literature,
      expression of CYP3A isoforms in human tissues and elimination of CYP3A substrates
      have not been shown to vary substantially by gender. There are no indications
      that the other CYP isoforms implicated in ET743 metabolism are expressed
      differently in males and females. Thus, although it is not possible to rule out
      gender differences in ET743 human toxicities, our data do not predict major
      gender-dependent differences in the toxicity of ET743 based on metabolism.

PMID- 12231542
TI  - Mebendazole elicits a potent antitumor effect on human cancer cell lines both in
      vitro and in vivo.
AB  - We have found that mebendazole (MZ), a derivative of benzimidazole, induces a
      dose- and time-dependent apoptotic response in human lung cancer cell lines. In
      this study, MZ arrested cells at the G(2)-M phase before the onset of apoptosis,
      as detected by using fluorescence-activated cell sorter analysis. MZ treatment
      also resulted in mitochondrial cytochrome c release, followed by apoptotic cell
      death. Additionally, MZ appeared to be a potent inhibitor of tumor cell growth
      with little toxicity to normal WI38 and human umbilical vein endothelial cells.
      When administered p.o. to nu/nu mice, MZ strongly inhibited the growth of human
      tumor xenografts and significantly reduced the number and size of tumors in an
      experimental model of lung metastasis. In assessing angiogenesis, we found
      significantly reduced vessel densities in MZ-treated mice compared with those in
      control mice. These results suggest that MZ is effective in the treatment of
      cancer and other angiogenesis-dependent diseases.

PMID- 12231543
TI  - Inhibition of oncogenic K-ras signaling by aerosolized gene delivery in a mouse
      model of human lung cancer.
AB  - PURPOSE: Transfer of growth-suppressive genes to lung tumors has therapeutic
      potential, but effective delivery techniques have not been developed. Here, we
      investigated gene delivery to lung tumors by aerosolization of adenoviral vectors
      incorporated into calcium phosphate precipitates. EXPERIMENTAL DESIGN: To
      investigate the efficacy of this delivery method in normal and neoplastic lung,
      an adenoviral vector expressing beta-galactosidase was administered by jet
      nebulization to K-ras(LA1) mice, which develop lung adenocarcinomas through
      activation of a latent allele carrying mutant K-ras(G12D). Furthermore, we
      investigated whether aerosolized delivery of Ad-MKK4 (KR), an adenoviral vector
      expressing dominant-negative mutant mitogen-activated protein kinase kinase
      4(MKK4), can block Ras-dependent signaling in K-ras(LA1) mice. RESULTS: After a
      single administration, beta-galactosidase was detected in lung tissue for up to
      21 days, and expression was much greater in tumors than in normal lung tissue.
      MKK4 was activated in the lungs of K-ras(LA1) mice, and aerosolized treatment
      with Ad-MKK4 (KR) decreased c-Jun-NH(2)-terminal kinase but not extracellular
      signal- regulated kinase activity, providing evidence that MKK4 was selectively
      inhibited. CONCLUSIONS: These findings demonstrate a novel approach to targeting
      oncogenic pathways in lung tumors by aerosolized gene delivery.

PMID- 12231544
TI  - Flavopiridol potentiates STI571-induced mitochondrial damage and apoptosis in BCR
      ABL-positive human leukemia cells.
AB  - PURPOSE: The goal of this study was to characterize interactions between the
      Bcr/Abl kinase inhibitor STI571 and the cyclin-dependent kinase inhibitor
      flavopiridol in Bcr/Abl(+) human leukemia cells. EXPERIMENTAL DESIGN: K562
      leukemia cells were exposed to STI571 +/- flavopiridol for 24 or 48 h, after
      which mitochondrial damage, caspase activation, expression/activation of
      signaling and cell cycle regulatory proteins, and apoptosis were assessed.
      RESULTS: In K562 cells, coadministration of marginally toxic concentrations of
      STI571 (200 nM) and flavopiridol (150 nM) for 48 h resulted in a marked increase
      in mitochondrial damage (e.g., cytochrome c release), activation of caspase-3,
      caspase-8, and Bid, and apoptosis. Similar interactions were observed in
      Bcr/Abl(+) LAMA-84 cells but not in leukemic cells that fail to express Bcr/Abl
      (e.g., HL-60, U937, Jurkat). STI571/flavopiridol-mediated apoptosis was
      associated with the caspase-independent down-regulation of Bcl-x(L) and Mcl-1,
      activation of extracellular signal-regulated kinase and c-Jun NH(2)-terminal
      kinase, and the caspase-dependent release of Smac/DIABLO and loss of deltapsi(m).
      Coadministration of flavopiridol and STI571 did not result in changes in levels
      of expression of Bcl-2, phopho-Stat5, phospho-p34(cdc2), or Bcr/Abl. Finally,
      STI571/flavopiridol effectively induced apoptosis in STI571-resistant K562 cells
      displaying amplification of the Bcr/Abl protein. CONCLUSIONS: Together, these
      findings indicate that the cyclin-dependent kinase inhibitor flavopiridol induces
      multiple perturbations in signaling pathways in STI571-treated Bcr/Abl(+) human
      leukemia cells that culminate in mitochondrial injury, caspase activation, and
      apoptosis. They also suggest that simultaneous disruption of survival signaling
      and cell cycle regulatory pathways may represent an effective strategy in
      Bcr/Abl(+) malignancies.

PMID- 12231545
TI  - Base excision repair as a therapeutic target in colon cancer.
AB  - Base excision repair (BER) is a fundamental cellular process used to reduce the
      cytotoxicity of alkylating agent chemotherapy. Heretofore, no therapeutic agents
      have targeted this DNA repair pathway. Methoxyamine (MX), which binds abasic
      sites, acting as an inhibitor of BER, was evaluated in combination with the
      methylating agent temozolomide (TMZ). Three human colon cancer cell lines were
      used, SW480 cells, which are wild-type for mismatch repair genes and have mutated
      p53, HCT116 cells, which are mutant in hMLH1 and wild-type for p53, and HCT15
      cells, which are mutant in hMSH6 and mutant in p53 as well. Nude mice carrying
      these tumors received TMZ alone or in combination with MX or O(6)-benzylguanine
      (BG), an inhibitor of O(6)-alkylguanine DNA-alkyltransferase, daily i.p. for 5
      consecutive days. At the highest tolerable dose of TMZ (120 mg/kg), a tumor
      growth delay of approximately 9.3 +/- 1.2 days was noted in SW480. Addition of BG
      resulted in a tumor growth delay of 25 +/- 2.4 days accompanied by significant
      weight loss (23%) and severe myelosuppression. In contrast, SW480 tumor-bearing
      mice treated with MX + TMZ had cessation of tumor growth for 50 +/- 13 days and
      very slow regrowth, yielding tumor growth delays of >70 +/- 14 days (P < 0.002)
      without additive systemic toxicity. HCT116 and HCT15 xenografts were completely
      resistant to treatment with TMZ alone or in combination with BG. However,
      treatment with MX + TMZ induced significant tumor growth delays (20 +/- 1.4 days
      in HCT116 and 14 +/- 3.1 days in HCT15 xenografts, P < 0.05). These studies
      demonstrate that a significant enhancement of the antitumor effect of TMZ by MX
      was observed in human colon cancer xenografts with mismatch repair proficiency
      and deficiency. DNA BER may be a useful pharmacological target through which
      tumor cells can be sensitized to alkylating therapeutic agents.

PMID- 12231546
TI  - Inter- and intratumoral disposition of platinum in solid tumors after
      administration of cisplatin.
AB  - One possible explanation for variable tumor response within a single patient may
      be related to delivery of chemotherapeutic agents to the tumors. Microdialysis
      was used to evaluate inter- and intratumoral disposition of unbound platinum (Pt)
      after cisplatin administration to mice bearing B16 murine melanoma tumors or H23
      human NSCLC xenografts. Before i.v. dosing with cisplatin (3 or 10 mg/kg),
      microdialysis probes were placed into the right and left sides of each tumor, and
      serial extracellular fluid (ECF) samples were collected for 2 h. After
      microdialysis, tumor samples were obtained at each probe site to measure total Pt
      and Pt-DNA adducts. In a separate study, serial plasma samples (n = 3 mice/time
      point) were obtained between 5 min and 2 h. Unbound Pt in tumor ECF and plasma
      and total Pt in tumor homogenates were measured by flameless atomic absorption
      spectrophotometry. Pt-DNA adducts in tumor samples were measured via (32)P
      postlabeling. Area under the plasma (AUC(P)) and tumor ECF (AUC(ECF))
      concentration-time curves of unbound Pt were calculated. Factor VIII expression
      was measured by immunohistochemistry in tumor samples. After administration of 3
      or 10 mg/kg of cisplatin to mice bearing B16 tumors, there was a proportional
      increase in AUC(PL) with dose; however, there was not a proportional increase in
      AUC(ECF). There was a relatively high (30-fold) inter- and low (2.5-fold)
      intratumoral variability in AUC(ECF). AUC(ECF) correlated better with Pt-DNA
      adduct formation than did total Pt concentration in tumors. There was no
      relationship between Factor VIII expression and Pt exposure in tumors. The
      variable penetration of Pt from plasma into tumor ECF may be associated with
      variable response of tumors.

PMID- 12231547
TI  - Relation between Irofulven (MGI-114) systemic exposure and tumor response in
      human solid tumor xenografts.
AB  - Irofulven is a novel, small molecular weight semisynthetic compound, derived from
      a family of mushroom toxins known as illudins. This DNA alkylating agent has a
      chemical structure unlike any other chemotherapeutic agent in clinical use. The
      molecule is currently being studied in several Phase I, II, and III trials. The
      objectives of this study were to evaluate the antitumor activity of Irofulven in
      a panel of 20 pediatric solid tumor xenografts and to relate the Irofulven
      systemic exposure, defined as area under the concentration time curve, to the
      antitumor dose associated with tumor regression in the tumor models. Irofulven
      was administered i.v. daily for 5 days with courses repeated every 21 days for a
      total of three cycles. The minimum effective dose of Irofulven causing objective
      regression (> or =50% volume regression) of advanced tumors was determined for
      each of 19 of 20 independently derived tumor models (12 brain tumors, 4
      neuroblastomas, and 4 rhabdomyosarcomas). At the maximum tolerated dose for three
      cycles of treatment (4.6 mg/kg/day) objective regressions were determined in 14
      of 18 tumor lines (78%). However, the dose-response relationship was acute. At 2
      mg/kg only 3 of 15 tumors tested demonstrated objective regressions, and in 3
      additional tumors volume regressions were not achieved at a higher dose level (3
      mg/kg), hence were not additionally tested. After administering the maximum
      tolerated dose (tolerated for one or two cycles of treatment) of Irofulven, 7
      mg/kg, to mice bearing sensitive and resistant human tumors plasma concentration
      time profiles were determined. Tumors were highly sensitive to Irofulven, but the
      systemic exposure required for a significant rate of objective response in this
      panel of tumors is in excess of that achievable in patients at tolerable doses,
      using this schedule of drug administration.

PMID- 12231548
TI  - The apurinic/apyrimidinic endonuclease activity of Ape1/Ref-1 contributes to
      human glioma cell resistance to alkylating agents and is elevated by oxidative
      stress.
AB  - Alkylating agents are standard components of adjuvant chemotherapy for gliomas.
      We provide evidence here that Ape1/Ref-1, the major mammalian
      apurinic/apyrimidinic endonuclease (Ap endo), contributes to alkylating agent
      resistance in human glioma cells by incising DNA at abasic sites. We show that
      antisense oligonucleotides directed against Ape1/Ref-1 in SNB19, a human glioma
      cell line lacking O(6)-methylguanine-DNA-methyltransferase, mediate both
      reduction in Ape1/Ref-1 protein and Ap endo activity and concurrent reduction in
      resistance to methyl methanesulfonate and the clinical alkylators temozolomide
      and 1,3-(2-chloroethyl)-1-nitrosourea. An accompanying increase in the level of
      abasic sites indicates that the DNA repair activity of Ape1/Ref-1 contributes to
      resistance. Conversely, we also show that exposure of SNB19 cells to HOCl, a
      generator of reactive oxygen species (ROS), results in elevated Ape1/Ref-1
      protein and Ap endo activity, enhanced alkylator resistance, and reduced levels
      of abasic sites. Given current evidence that heightened oxidative stress prevails
      within brain tumors, the finding that ROS increase resistance to clinical
      alkylators in glioma cells may have significance for the response of gliomas to
      alkylating agent-based chemotherapy. Our results may also be relevant to the
      design of therapeutic regimens using concurrent ionizing radiation (a generator
      of ROS) and alkylating agent-based chemotherapy.

PMID- 12231550
TI  - Retraction.

PMID- 12231549
TI  - Both protein activation and gene expression are involved in early vascular tube
      formation in vitro.
AB  - PURPOSE: Gene expression and protein translation regulate and direct endothelial
      cell proliferation and differentiation. We initiated an unbiased global search
      for transcriptional changes occurring during endothelial cell vascular
      differentiation in vitro, focusing on genes not previously implicated in
      vascularization and angiogenesis. EXPERIMENTAL DESIGN: cDNA and protein from
      human umbilical vein endothelial cells forming vascular tubes on the basement
      membrane surrogate, Matrigel, were collected and subjected to a global unbiased
      search for alterations in expression of genes not previously linked to
      angiogenesis. RESULTS: Transcriptional inhibitors blocked vascular tube formation
      only when present within the first hour of incubation (P < 0.05). cDNA array
      analysis yielded 31 differentially regulated transcripts (of 5100 queried; false
      positive rate, 0.4%) from gene classes representing transcription, translational
      regulation, cell structure, and cell adhesion. mRNA levels of caldesmon, a
      cytoskeleton-associated protein not previously linked to angiogenesis, were
      markedly reduced during early tube formation. Caldesmon protein quantity was also
      markedly decreased as demonstrated by laser capture microdissection of tubule
      cells followed by immunoblotting. Strikingly, no significant changes in
      transcription of genes previously demonstrated to contribute to angiogenesis,
      invasion, or signal transduction contained on the array were observed. To
      investigate the possibility that posttranslational rather than transcriptional
      changes were involved in facilitating tube formation, we evaluated the activation
      status of two dominant signal pathways, RAS/mitogen-activated protein kinase and
      phosphatidylinositol 3-kinase/AKT. A net 3-fold reduction in phospho-AKT and a 4
      fold reduction in phospho-extracellular signal-regulated kinase-1/2 occurred in a
      transcription-independent fashion. CONCLUSIONS: These data suggest that both
      changes in gene expression and transcription-independent activation of signal
      transduction pathways may be involved in vascular tube formation. A combination
      of transcriptional and proteomic analysis has the potential to identify novel
      transcription-dependent and -independent molecular targets of angiogenesis.

PMID- 12231551
TI  - Lysyl oxidase: new looks on LOX.

PMID- 12231552
TI  - Toward understanding of extracellular superoxide dismutase regulation in
      atherosclerosis: a novel role of uric acid?

PMID- 12231553
TI  - A simple experiment and a weakening paradigm: the contribution of blood to
      propensity for thrombus formation.

PMID- 12231554
TI  - Progression of atheroma: a struggle between death and procreation.
AB  - Traditional thinking accorded a major role to deranged cell proliferation as a
      determinant of the abnormal cellularity of atheroma. However, studies conducted
      in several laboratories have documented the occurrence of disordered apoptosis
      during atherogenesis, leading to the death of lipid-rich foam cells (promoting
      lipid-core formation) and depletion of vascular smooth muscle cells (fostering
      fragility of the fibrous cap). A complex interplay of environmental factors and
      endogenous proteins regulates apoptosis and contributes to the struggle between
      cell death and procreation in atherosclerosis. In addition to a variety of growth
      factors, chemically modified lipids, reactive oxygen species, proinflammatory
      cytokines, and Fas ligand produced by activated immune cells may influence cell
      viability through a diversity of pathways, including the caspase cascade, the Bcl
      2 protein family, and the oncogene/antioncogene system. A clarification of the
      molecular mechanisms responsible for vascular cell death may aid in the
      development of novel therapeutic strategies to treat atherosclerosis and its
      complications, including the acute coronary syndromes.

PMID- 12231555
TI  - Platelets and thrombin generation.
AB  - This review examines the evidence that platelets play a major role in localizing
      and controlling the burst of thrombin generation leading to fibrin clot
      formation. From the first functional description of platelets, it has been
      recognized that platelets supply factors that support the activation of
      prothrombin. Studies have demonstrated that on activation, the amount of one
      specific lipid, phosphatidylserine, is significantly increased on the outer
      leaflet of platelet membranes. When it was found that phosphatidylserine
      containing lipid extracts could be substituted for platelets in clotting assays,
      this suggested the possibility that changes in platelet lipid composition were
      necessary and sufficient to account for platelet surface thrombin generation.
      Because a growing body of data suggest that platelet-binding proteins provide
      much of the specificity for platelet thrombin generation, we review in this
      report data suggesting that changes in lipid composition are necessary but not
      sufficient to account for platelet surface regulation of thrombin generation.
      Also, we review data suggesting that platelets from different individuals differ
      in their capacity to generate thrombin, whereas platelets from a single subject
      support thrombin generation in a reproducible manner. Individual differences in
      platelet thrombin generation might be accounted for by differences in platelet
      binding proteins.

PMID- 12231556
TI  - Quantitative trait loci and candidate genes regulating HDL cholesterol: a murine
      chromosome map.
AB  - OBJECTIVE: Summarizing the many discovered mouse and human quantitative trait
      loci (QTL) for high density lipoprotein (HDL) cholesterol (HDL-C) levels is
      important for guiding future research on the genetic regulation of HDL
      concentrations and for finding gene targets for upregulating HDL levels in mice
      and humans. METHODS AND RESULTS: We summarized the 27 QTL and candidate genes
      associated with HDL-C concentrations in mice and plotted them on a mouse
      chromosome map. We also summarized the 22 human QTL for HDL-C levels and compared
      them with those of the mouse by comparative genomics. At least part of the mouse
      homologies for 18 of the 22 human HDL-C QTL were within the murine HDL-C QTL.
      CONCLUSIONS: Murine QTL for HDL-C levels may predict their homologous location in
      humans, and their underlying genes may be appropriate genes to test in humans.

PMID- 12231557
TI  - Peroxidase properties of extracellular superoxide dismutase: role of uric acid in
      modulating in vivo activity.
AB  - OBJECTIVE: The cytosolic form of Cu/Zn-containing superoxide dismutase (SOD1) has
      peroxidase activity, with H2O2 used as a substrate to oxidize other molecules. We
      examined peroxidase properties of the extracellular form of SOD (SOD3), a major
      isoform of SOD in the vessel wall, by using recombinant SOD3 and an in vivo model
      of atherosclerosis. METHODS AND RESULTS: In the presence of HCO3-, SOD3 reacted
      with H2O2 to produce a hydroxyl radical adduct of the spin trap 5
      diethoxyphosphoryl-5methyl-1-pyrroline N-oxide (DEMPO). SOD1 and SOD3 were
      inactivated by H2O2 in a dose- and time-dependent fashion, and this was prevented
      by physiological levels of uric acid. To examine the in vivo role of uric acid on
      SOD1 and SOD3, control and apolipoprotein E-deficient (ApoE(-/-)) mice were
      treated with oxonic acid, which inhibits urate metabolism. This treatment
      increased plasma levels of uric acid in control and ApoE(-/-) mice by
      approximately 3-fold. Although increasing uric acid levels did not alter aortic
      SOD1 and SOD3 protein expression, aortic SOD1 and SOD3 activities were increased
      by 2- to 3-fold in aortas from ApoE(-/-) mice but not in aortas from control
      mice. CONCLUSIONS: These studies show that SOD1 and SOD3 are partially
      inactivated in atherosclerotic vessels of ApoE(-/-) mice and that levels of uric
      acid commonly encountered in vivo may regulate vascular redox state by preserving
      the activity of these enzymes.

PMID- 12231558
TI  - Low density lipoproteins downregulate lysyl oxidase in vascular endothelial cells
      and the arterial wall.
AB  - OBJECTIVE: Hypercholesterolemia induces endothelial dysfunction, a hallmark of
      the atherosclerotic process, modulating the expression of key genes in vascular
      endothelial cells. METHODS AND RESULTS: By differential display analysis, we have
      studied the effect of high concentrations of native low density lipoprotein (LDL)
      on endothelial gene expression. mRNA levels of lysyl oxidase (LOX), an enzyme
      involved in collagen and elastin cross-linking, were downregulated by LDL
      treatment in endothelial cells in a dose- and time-dependent manner (80% of
      inhibition by 180 mg/dL LDL for 24 hours). This reduction of LOX expression was
      associated with a decrease in LOX activity (40% and 54% of inhibition after 24
      and 48 hours of LDL treatment, respectively). LOX mRNA half-life was not modified
      by LDL, but transcriptional inhibition blocked the effect of LDL. Inhibition of
      LOX activity by either LDL or beta-aminopropionitrile, an inhibitor of LOX,
      increased endothelial permeability (192+/-0.19- and 3.37+/-0.74-fold,
      respectively). Interestingly, a reduction in LOX expression (3.5-fold) was
      observed in vivo in the vascular wall of hypercholesterolemic pigs. CONCLUSIONS:
      These findings suggest that LDL downregulation of LOX could contribute to the
      endothelial dysfunction caused by hypercholesterolemia, thus contributing to
      atherosclerotic plaque formation.

PMID- 12231559
TI  - Transcriptional and posttranscriptional regulation of cyclooxygenase-2 expression
      by fluid shear stress in vascular endothelial cells.
AB  - OBJECTIVE: Fluid shear stress induces cyclooxygenase (COX)-2 gene expression in
      vascular endothelial cells. We investigated the underlying mechanism of this
      induction. METHODS AND RESULTS: Exposure of human umbilical vein endothelial
      cells to laminar shear stress in the physiological range (1 to 30 dyne/cm2)
      upregulated the expression of COX-2 but not COX-1, a constitutive isozyme of COX.
      The expression of COX-2 mRNA began to increase within 0.5 hour after the loading
      of shear stress and reached a maximal level at 4 hours. Roles of the promoter
      region and the 3'-untranslated region in the human COX-2 gene were evaluated by
      the transient transfection of luciferase reporter vectors into bovine arterial
      endothelial cells. Shear stress elevated luciferase activity via the region
      between -327 and 59 bp. Mutation analysis indicated that cAMP-responsive element
      (-59/-53 bp) was mainly involved in this response. On the other hand, shear
      stress selectively stabilized COX-2 mRNA. Moreover, shear stress elevated
      luciferase activity when a 3'-untranslated region of COX-2 gene containing 17
      copies of the AUUUA mRNA instability motif was inserted into the vector.
      CONCLUSIONS: Transcriptional activation and posttranscriptional mRNA
      stabilization contribute to the rapid and sustained expression of COX-2 in
      response to shear stress.

PMID- 12231561
TI  - Connexin37 is the major connexin expressed in the media of caudal artery.
AB  - OBJECTIVE: To determine the connexins (Cxs) involved in intercellular coupling
      within vascular muscle, the present study has quantified mRNA and protein
      expression for Cx37, Cx40, Cx43, and Cx45 in the caudal artery (CA) and thoracic
      aorta (ThA) of the rat. METHODS AND RESULTS: Real-time polymerase chain reaction
      and immunohistochemistry identified Cx37 as the most abundantly expressed Cx in
      the CA, with fine punctate staining observed in the media. Conversely, mRNA for
      Cx43 was 40-fold greater in the ThA than in the CA, with punctate staining in the
      endothelium and media of the ThA but confined to the endothelium in the CA.
      Western blotting confirmed the differences in the relative amounts of Cx43
      between the 2 vessels. For both arteries, Cx45 was expressed to a lesser degree
      in the media but not in the endothelium, whereas Cx40 was found only in the
      endothelium. Cx37, Cx40, and Cx43 were expressed in the endothelium of both
      vessels, although the density of Cx40 plaques was significantly greater in the
      CA. CONCLUSIONS: The demonstration of Cx37 as the dominant Cx in the media of the
      CA highlights the potential heterogeneity in Cx involvement in vascular smooth
      muscle.

PMID- 12231560
TI  - Plasmin induces Cyr61 gene expression in fibroblasts via protease-activated
      receptor-1 and p44/42 mitogen-activated protein kinase-dependent signaling
      pathway.
AB  - OBJECTIVE: The plasminogen system has been proposed to participate in vascular
      remodeling and angiogenesis. Although plasmin-mediated proteolysis could
      contribute these processes, proteolytic targets for plasmin and their downstream
      effector molecules are yet to be fully defined. The aim of the present study was
      to elucidate potential mechanisms by which plasmin affects various cellular
      processes. METHODS AND RESULTS: Plasmin upregulated the expression of Cyr61, a
      growth factor-like gene that has been implicated in cell proliferation, adhesion,
      and migration. Plasmin-induced gene expression is dependent on its proteolytic
      activity and requires its binding to cells. Studies that used wild-type
      fibroblasts and fibroblasts derived from PAR-1- and PAR-2-deficient mice showed
      that plasmin induced Cyr61 gene expression in wild-type fibroblasts and PAR-2
      deficient cells but not in PAR-1-deficient cells. Consistent with this, plasmin
      induced the activation of p44/42 mitogen-activated protein kinase in wild-type,
      PAR-2 -/- cells but not in PAR-1 -/- cells. In contrast with thrombin, plasmin
      failed to induce Ca2+ signaling in fibroblasts. CONCLUSIONS: Plasmin induced an
      angiogenic and wound-healing promoter, Cyr61, in fibroblasts through activation
      of PAR-1. Plasmin-induced Cyr61 expression is mediated via the p44/42 mitogen
      activated protein kinase pathway independent of Ca2+ signaling.

PMID- 12231562
TI  - Inhibition of accelerated atherosclerosis in vein grafts by placement of external
      stent in apoE*3-Leiden transgenic mice.
AB  - OBJECTIVE: Vein grafts fail because of the development of intimal hyperplasia and
      accelerated atherosclerosis. Placement of an external stent around vein grafts
      resulted in an inhibition of intimal hyperplasia in several animal studies. Here,
      we assess the effects of external stenting on accelerated atherosclerosis in
      early vein grafts in carotid arteries in hypercholesterolemic apolipoprotein E*3
      Leiden transgenic mice. METHODS AND RESULTS: Venous interposition grafting was
      performed in apolipoprotein E*3-Leiden mice fed standard chow or a highly
      cholesterol-rich diet for 4 weeks. After engraftment, external stents with
      different inner diameters (0.4 or 0.8 mm) were placed. In unstented vein grafts
      in hypercholesterolemic mice, thickening up to 50 times the original thickness,
      with foam cell-rich lesions, calcification, and necrosis, was observed within 28
      days. The atherosclerotic lesions observed show high morphological resemblance to
      atherosclerotic lesions observed in human vein grafts. In stented vein grafts in
      hypercholesterolemic mice, no foam cell accumulation or accelerated
      atherosclerosis was observed. Compared with unstented vein grafts, stenting of
      vein grafts in a hypercholesterolemic environment resulted in a 94% reduction of
      vessel wall thickening. These effects were independent of stent size.
      CONCLUSIONS: Extravascular stent placement results in strong inhibition of
      accelerated vein graft atherosclerosis in hypercholesterolemic transgenic mice
      and thereby provides a perspective for therapeutic intervention in vein graft
      diseases.

PMID- 12231563
TI  - Contribution of double-stranded RNA-activated protein kinase toward
      antiproliferative actions of heparin on vascular smooth muscle cells.
AB  - OBJECTIVE: The proliferation of vascular smooth muscle cells (VSMCs) in blood
      vessels after endothelial injury contributes to the onset of atherosclerosis.
      Heparin is a potent antiproliferative agent for VSMCs in vivo and in vitro.
      Although heparin has shown promise in suppressing VSMC proliferation after
      invasive procedures in laboratory animals, the mechanism of its antiproliferative
      actions is largely unknown. Here, we present evidence for the first time that the
      antiproliferative action of heparin is in part mediated by its ability to
      activate double-stranded RNA-activated protein kinase (PKR), an interferon
      induced protein kinase. METHODS AND RESULTS: We have analyzed the VSMC
      proliferation by cell-cycle analysis and correlated it to the kinase activity of
      PKR in the presence of heparin. Heparin treatment of VSMCs results in activation
      of PKR by direct binding and results in a block in G1- to S-phase transition. PKR
      null cells are largely insensitive to the antiproliferative actions of heparin,
      and inhibition of PKR in VSMCs results in a partial abrogation of the
      antiproliferative effects of heparin. CONCLUSIONS: These results invoke the
      involvement of novel PKR-dependent regulatory pathways in mediating the
      antiproliferative actions of heparin.

PMID- 12231564
TI  - Inhibition of renin-angiotensin system ameliorates endothelial dysfunction
      associated with aging in rats.
AB  - OBJECTIVE: Endothelial vasodilator functions are progressively impaired with
      aging, which may account in part for the increased incidence of cardiovascular
      events in elderly people. We examined what treatment could ameliorate the
      endothelial dysfunction associated with aging in rats. METHODS AND RESULTS: Aged
      (12-month-old) Wistar-Kyoto rats were treated with vehicle, temocapril, CS-866
      (an angiotensin II type 1 receptor antagonist), cerivastatin, or hydralazine for
      2 weeks. Endothelium-dependent relaxations (EDRs) of aortas from aged rats were
      markedly impaired compared with EDRs of aortas from young (3-month-old) rats.
      Indomethacin, NS-398 (a cyclooxygenase [COX]-2 inhibitor), and SQ-29548 (a
      thromboxane A2/prostaglandin H2 receptor antagonist) acutely restored EDRs in
      aged rats, suggesting an involvement of COX-2-derived vasoconstricting
      eicosanoids. Tiron, a superoxide scavenger, also partially improved EDRs,
      suggesting an involvement of superoxide. EDRs were significantly ameliorated in
      aged rats after long-term treatment with temocapril or CS-866 but not after
      treatment with cerivastatin or hydralazine. Indomethacin induced no further
      improvement of EDRs after treatment with temocapril or CS-866. COX-2 protein
      expression and superoxide production were increased in the aortas of aged rats
      and were also attenuated by treatment with temocapril or CS-866. CONCLUSIONS:
      These results demonstrate that long-term inhibition of the renin-angiotensin
      system ameliorates endothelial dysfunction associated with aging through the
      inhibition of the synthesis of COX-2-derived vasoconstricting factors and
      superoxide anions.

PMID- 12231565
TI  - Statins reduce inflammation in atheroma of nonhuman primates independent of
      effects on serum cholesterol.
AB  - OBJECTIVE: Some of the statin-induced reduction in cardiac events in patients
      with atherosclerosis may be derived from mechanisms independent of lipid
      lowering. This study tested in nonhuman primates whether statins can influence
      inflammation (indicated by vascular cell adhesion molecule-1, interleukin-1beta,
      tissue factor, and macrophages) and features of plaque stability (indicated by
      collagen and smooth muscle cells) independent of their effect on plasma
      cholesterol level. METHODS AND RESULTS: Adult male cynomolgus monkeys (n=12 per
      group) consumed an atherogenic diet for 12 months while receiving (1) no
      treatment (control), (2) pravastatin (Prava, 40 mg/kg per day), or (3)
      simvastatin (Simva, 20 mg/kg per day). Dietary cholesterol was adjusted to
      equalize plasma cholesterol levels among groups. Although the intima/media ratio
      in the abdominal aorta did not differ among groups, drug treatment reduced
      inflammation and features of plaque vulnerability. Macrophage content in the
      lesions of statin-treated animals was lowered (2.4-fold with Prava and 1.3-fold
      with Simva; both P<0.001 versus control). Furthermore, lesions had approximately
      2-fold less vascular cell adhesion molecule-1, interleukin-1beta, and tissue
      factor expression in statin-treated versus control animals (P<0.005). Lesional
      smooth muscle cell and collagen content was 2.1-fold greater in the Prava-treated
      group (P<0.001) and 1.5-fold greater in the Simva-treated group (P<0.005) than in
      the control group. CONCLUSIONS: In primates, these results provide further
      support for the beneficial effect of statins on plaque inflammation and stability
      in addition to cholesterol lowering.

PMID- 12231566
TI  - Effects of continuous combined hormone replacement therapy on inflammation in
      hypertensive and/or overweight postmenopausal women.
AB  - OBJECTIVE: We observed that estrogen did not show cardioprotective benefits in
      type 2 diabetic postmenopausal women. We hypothesized that hypertensive and/or
      overweight women may be less likely to realize cardiovascular benefits from
      estrogen. METHODS AND RESULTS: We administered micronized progesterone (MP) 100
      mg or medroxyprogesterone acetate (MPA) 2.5 mg with conjugated equine estrogen
      (CEE) 0.625 mg daily during 2 months to 35 hypertensive and/or overweight
      postmenopausal women with a randomized, double-blind, crossover design. With
      significant changes of lipoproteins, CEE+MP or MPA significantly improved flow
      mediated dilation and reduced plasma E-selectin, intercellular adhesion molecule
      type-1, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha
      levels (P<0.001, P<0.001, P=0.021, P<0.001, and P<0.001 by ANOVA, respectively),
      but not C-reactive protein and fibrinogen levels. Of note, there were no
      significant differences between each therapy regarding these effects. However,
      the magnitude of improvement of flow-mediated dilation in these women was less
      than in healthy postmenopausal women and more than in diabetic postmenopausal
      women reported by our previous studies. The effects of CEE+MP or MPA on
      inflammatory markers were comparable to healthy postmenopausal women, but not
      comparable to diabetic postmenopausal women. CONCLUSIONS: Estrogen combined with
      synthetic progestin significantly improved flow-mediated brachial artery dilator
      response and reduced inflammation markers in hypertensive and/or overweight
      women, comparable to estrogen combined with natural progesterone.

PMID- 12231567
TI  - Relationship between cholesteryl ester transfer protein and atherogenic
      lipoprotein profile in morbidly obese women.
AB  - OBJECTIVE: Obesity is associated with increased morbidity and mortality from
      atherosclerotic disease. Lipid abnormalities contribute to the increased relative
      risk in obese subjects. Cholesteryl ester transfer protein (CETP) mass is
      increased in these patients and might mediate the atherogenic lipoprotein pattern
      observed in obesity. METHODS AND RESULTS: Twenty-one morbidly obese, middle-aged,
      female subjects participated in this prospective study. Subjects were examined
      before and 1 year after surgical treatment. Fat mass was determined by body
      impedance analysis; CETP mass, by ELISA; CETP activity, by exogenous substrate
      assay; and LDL particle diameter, by gradient gel electrophoresis. Mean weight
      loss after 1 year was 28.7 kg; mean fat mass loss was 22.6 kg. Mean CETP mass
      decreased from 1.81 to 1.32 microg/mL (P=0.008); mean CETP activity decreased
      from 244 to 184 nmol x mL(-1) x h(-1) (P=0.004); and in parallel, the mean
      diameter of LDL particles increased (256.8 to 258.4 A, P=0.04). CONCLUSIONS: We
      conclude that weight loss is associated with a pronounced decrease in CETP mass
      and activity and a consistent increase in LDL particle diameter. After 1 year of
      this prospective study in morbidly obese subjects undergoing weight loss by
      surgical treatment, it has been determined that some features of the atherogenic
      lipoprotein profile can be reversed.

PMID- 12231568
TI  - Postprandial enrichment of remnant lipoproteins with apoC-I in healthy
      normolipidemic men with early asymptomatic atherosclerosis.
AB  - OBJECTIVES: Recently, we reported that exaggerated postprandial triglyceridemia
      in normolipidemic patients with coronary artery disease is associated with
      enrichment of remnant lipoproteins with apolipoprotein C-I (apoC-I). In this
      study, the number and composition of chylomicron remnants and very low density
      lipoproteins (VLDLs) were examined in 30 asymptomatic normolipidemic 50-year-old
      men with and without early carotid atherosclerotic lesions. METHODS AND RESULTS:
      Intima-media thickness of the far wall of the common carotid artery was
      determined by B-mode ultrasound. Triglyceride-rich lipoproteins were
      subfractionated by density gradient ultracentrifugation and separated into VLDL
      and chylomicron remnant fractions by immunoaffinity chromatography. The
      postprandial triglyceridemia and increase in triglyceride-rich lipoprotein
      particle number (ie, apolipoprotein B concentrations) were not exaggerated in men
      with early atherosclerosis. In contrast, their large (Svedberg flotation rate 60
      to 400) and small (Svedberg flotation rate 20 to 60) chylomicron remnants and
      VLDL were greatly enriched with apoC-I, and their small chylomicron remnants and
      VLDL particles were relatively enriched with cholesterol. Moreover, the number of
      apoC-I molecules on small chylomicron remnants was strongly associated with the
      degree of atherosclerosis. CONCLUSIONS: Early asymptomatic atherosclerosis in
      normolipidemic men without exaggerated postprandial triglyceridemia is associated
      with the enrichment of postprandial chylomicron and VLDL particles with apoC-I.
      Therefore, it is conceivable that the apoC-I content of lipoprotein remnants may
      serve as an early marker of coronary artery disease risk.

PMID- 12231569
TI  - Mast cell chymase degrades apoE and apoA-II in apoA-I-knockout mouse plasma and
      reduces its ability to promote cellular cholesterol efflux.
AB  - OBJECTIVE: Mast cell chymase is a chymotryptic heparin proteoglycan-bound neutral
      protease that exerts its activity in extracellular fluids. We studied the effect
      of chymase on the apolipoprotein compositions and the abilities of plasmas from
      apolipoprotein (apo)A-I-knockout (A-I-KO) and wild-type (C57BL/6J) mice to
      stimulate efflux of cellular cholesterol from mouse macrophage foam cells.
      METHODS AND RESULTS: The A-I-KO apolipoproteins compared with the wild-type (apoA
      I, apoA-II, apoA-IV, and apoE) showed total lack of apoA-I, unaltered apoA-II, an
      absence of apoA-IV, and an increase of apoE. Despite these major differences, the
      2 plasmas induced similar high-affinity efflux of cholesterol from the foam
      cells. Quantitative analysis of chymase-treated plasmas revealed (1) in A-I-KO
      plasma, complete loss of apoE and apoA-II, and (2) in wild-type plasma, slight
      reduction of apoA-I associated with complete depletion of the minor pre-beta-high
      density lipoprotein fraction, strong reduction of apoA-II, and complete depletion
      of apoA-IV and apoE. Both proteolyzed plasmas had lost the ability to induce
      cellular cholesterol efflux with high affinity. Addition of discoidal pre-beta
      migrating reconstituted high density lipoprotein particles containing human apoA
      I or apoA-II to the chymase-treated A-I-KO plasma fully restored its cholesterol
      efflux-inducing ability, indicating functional replacement of the proteolyzed
      apoE and apoA-II. Thus, chymase degraded all the nondeleted apolipoproteins of
      the A-I-KO plasma involved in the high-affinity efflux of cellular cholesterol.
      CONCLUSIONS: This is the first indication that genetically engineered mice could
      be used as models for examining the hypothesis that extracellular proteases are
      involved in the development of atherosclerosis by inhibiting the apolipoprotein
      mediated removal of macrophage cholesterol.

PMID- 12231570
TI  - Delineation of the role of pre-beta 1-HDL in cholesterol efflux using isolated
      pre-beta 1-HDL.
AB  - OBJECTIVE: The role of pre-beta1-high density lipoprotein (pre-beta1-HDL) in
      cholesterol efflux was investigated by separating human plasma into purified pre
      beta1-HDL and pre-beta1-HDL-deficient plasma by using a monoclonal antibody
      specifically reacting with pre-beta1-HDL. METHODS AND RESULTS: When compared with
      whole plasma, pre-beta1-HDL-deficient plasma was equally efficient in promoting
      cholesterol efflux from human skin fibroblasts and THP-1 human macrophage cells.
      When added at the same apolipoprotein A-I concentration, pre-beta1-HDL was less
      effective than whole plasma in promoting cholesterol efflux from fibroblasts but
      equally effective in promoting cholesterol efflux from THP-1 cells. However, pre
      beta1-HDL-deficient plasma reconstituted with 16% pre-beta1-HDL was more active
      than whole plasma, demonstrating that pre-beta1-HDL does promote cholesterol
      efflux actively. The amount of cellular cholesterol present in reisolated pre
      beta1-HDL was 1.5- to 2-fold greater after incubation of the cells with whole
      plasma than after incubation of the cells with pre-beta1-HDL-deficient plasma or
      plasma treated with the anti-pre-beta1-HDL antibody. However, the anti-pre-beta1
      HDL antibody did not inhibit cholesterol efflux. CONCLUSIONS: We conclude that
      whereas pre-beta1-HDL is capable of taking up cellular cholesterol, its presence
      in plasma is not essential for cholesterol efflux, at least in vitro. Instead,
      pre-beta1-HDL may be the first product of apolipoprotein A-I lipidation during
      the formation of HDL but may not play a major role in transferring cellular
      cholesterol to HDL.

PMID- 12231571
TI  - Microsomal triglyceride transfer protein gene expression and triglyceride
      accumulation in hypoxic human hearts.
AB  - OBJECTIVES: Cardiac myocytes secrete apolipoprotein (apo)B-containing
      lipoproteins. Their function may be the removal of triglycerides when beta
      oxidation of fatty acids is decreased, eg, during hypoxia. To test this
      hypothesis, we examined heart biopsies from patients undergoing coronary artery
      bypass graft (CABG, n=13) or valve replacement (n=6) surgery. METHODS AND
      RESULTS: Ventricular microsomal triglyceride transfer protein (P=0.02) and apoB
      (P=0.04) mRNA levels were both approximately 2-fold higher in CABG compared with
      valve replacement patients. In CABG patients, ventricular microsomal triglyceride
      transfer protein mRNA levels were negatively associated with the triglyceride
      content in ventricular myocytes (r=-0.70; P=0.02) and with mRNA levels of sterol
      regulatory element binding protein-1 (r=-0.74; P=0.004). CONCLUSIONS: The results
      are compatible with the notion that cardiac lipoprotein production is increased
      in hypoxic human ventricle, possibly as a result of decreased sterol regulatory
      element binding protein-1 expression. This might attenuate accumulation of
      triglycerides in cardiac myocytes.

PMID- 12231572
TI  - Factors contributing to individual propensity for arterial thrombosis.
AB  - OBJECTIVE: Occurrence of arterial thrombosis secondary to vascular disease in an
      individual is not easily predicted. After establishing that this poor
      predictability arises at least in part from an intrinsic thrombosis propensity of
      the individual, we sought to determine whether the propensity for arterial
      thrombosis is governed by blood or arterial wall factors. METHODS AND RESULTS: To
      evaluate the variability arising from the blood, autologous 111In-labeled
      platelet deposition was measured after high-shear perfusion of compressed aortic
      strips, prepared from a single pig, with heparinized blood from 25 pigs. To
      evaluate the variability arising from the vessel wall, aortic strips from 8 pigs
      were superfused with blood from a single animal. Blood samples from 25 animals
      superfused over aortic substrate from a single source yielded a 24-fold range of
      platelet deposition. In contrast, when aortic substrates from 8 different animals
      were superfused with blood from a single animal, platelet deposition spanned a 3
      fold range. Platelet deposition was significantly correlated with whole-blood
      lymphocyte counts and with platelet counts. CONCLUSIONS: Individual propensity
      for arterial thrombosis in pigs is more greatly influenced by blood components
      than by elements within the arterial wall.

PMID- 12231573
TI  - Analysis of coagulation cascade and endothelial cell activation during inhibition
      of vascular endothelial growth factor/vascular endothelial growth factor receptor
      pathway in cancer patients.
AB  - OBJECTIVE: The angiogenesis inhibitor SU5416 is a potent inhibitor of vascular
      endothelial growth factor (VEGF) receptor-1 and -2. VEGF may be involved in
      hemostasis by altering the hemostatic properties of endothelial cells. We
      analyzed the effects of SU5416 on the coagulation cascade and the vessel wall in
      patients with advanced cancer. METHODS AND RESULTS: Markers for thrombin
      generation, activation of the protein C pathway, fibrinolysis, and endothelial
      cell activation were measured in patients with renal cell carcinoma, soft tissue
      sarcoma, or melanoma on days 0, 14, and 28 of treatment with SU5416. Three of 17
      sampled patients developed a thromboembolic event in the fifth week of treatment.
      Markers for thrombin generation and fibrinolysis did not show significant
      changes. We observed a significant increase in endogenous thrombin potential and
      of parameters reflecting endothelial cell activation (von Willebrand antigen,
      soluble tissue factor, and soluble E-selectin) in all patients (P< or =0.001). In
      patients experiencing a thromboembolic event, endogenous thrombin potential,
      soluble tissue factor, and soluble E-selectin increased to a significantly
      greater extent (P=0.029, P=0.021, and P=0.007, respectively). CONCLUSIONS: VEGF
      is not only a permeability, proliferation, and migration factor, but it is also a
      maintenance and protection factor for endothelial cells.

PMID- 12231574
TI  - In memoriam Donald S. Fredrickson, MD: 1924-2002.

PMID- 12231576
TI  - Calcification of bicuspid aortic valves.

PMID- 12231577
TI  - Anomalous origin of left anterior descending and circumflex coronary artery from
      two separate ostia in the right aortic sinus.

PMID- 12231575
TI  - Comparative effects of diet and statin on NO bioactivity and matrix
      metalloproteinases in hypercholesterolemic patients with coronary artery disease.
AB  - OBJECTIVE: We investigated the effects of statin compared with the American Heart
      Association (AHA) Step I Diet on lipoproteins, vasomotor function, tumor necrosis
      factor (TNF)-alpha, and serological markers of plaque stability. Furthermore, we
      investigated the mechanism of regulation suggested by experimental studies.
      METHODS AND RESULTS: For 14 weeks, we administered AHA diet+placebo and AHA
      diet+simvastatin (20 mg daily) to 31 and 32 randomly selected patients with
      coronary artery disease, respectively. Compared with diet alone, simvastatin
      significantly improved the percent flow-mediated dilator response to hyperemia
      from 3.37+/-2.28% to 5.89+/-2.35% (P<0.001) and lowered plasma levels of C
      reactive protein from 0.48 to 0.10 mg/dL (P<0.001), TNF-alpha from 3.38 to 2.79
      pg/mL (P<0.001), total matrix metalloproteinase (MMP)-9 from 36 to 28 ng/mL
      (P=0.006), and tissue inhibitor of matrix metalloproteinase-1 from 80+/-30 to
      74+/-23 ng/mL (P=0.041), and simvastatin lowered to a greater extent MMP-9
      activity (from 71 to 52 ng/mL, P=0.006) and MMP-9 activity/tissue inhibitor of
      matrix metalloproteinase-1 ratios (P=0.018), although this difference did not
      reach statistical significance. There were significant correlations between the
      degree of changes in TNF-alpha and the degree of changes in MMP-9 activity
      (r=0.424, P=0.016). However, no significant correlations between lipoprotein
      levels or flow-mediated dilation percentages and levels of plaque stability
      markers were determined (-0.208< or =r< or =0.243). CONCLUSIONS: Simvastatin
      reduced serological markers of inflammation and plaque stability, independent of
      lipoprotein changes.

PMID- 12231578
TI  - Prognostic importance of right ventricular dysfunction.

PMID- 12231580
TI  - Right coronary artery aneurysm diagnosed with multislice computed tomographic
      angiography.

PMID- 12231579
TI  - The right atrium as an anatomic set-up for re-entry: electrophysiology goes back
      to anatomy.

PMID- 12231581
TI  - The complex link between brain and heart in cardiac syndrome X.

PMID- 12231582
TI  - Microvascular obstruction and missed infarction.

PMID- 12231583
TI  - Heparin dose during percutaneous coronary intervention: how low dare we go?
AB  - Despite dramatic advances in percutaneous coronary intervention, including
      coronary stents and potent antiplatelet agents, unfractionated heparin remains
      the standard procedural anticoagulant. Tradition and habit may have considerable
      influence over dose selection. A review of the role and dosage of heparin during
      PCI appears to be overdue

PMID- 12231584
TI  - ST segment monitoring of coronary reperfusion.

PMID- 12231585
TI  - Rheology of discrete subaortic stenosis.
AB  - The discrete form of subaortic stenosis is thought to be an acquired lesion, the
      aetiology of which may be a combination of factors which include an underlying
      genetic predisposition, turbulence in the left ventricular outflow tract, and
      various geometric and anatomical variations of the left ventricular outflow
      tract. A review of hypotheses relating to its aetiology is provided

PMID- 12231586
TI  - Changing the diagnostic criteria for myocardial infarction in patients with a
      suspected heart attack affects the measurement of 30 day mortality but not long
      term survival.
AB  - OBJECTIVES: To explore the effects of alternative methods of defining myocardial
      infarction on the numbers and survival patterns of patients identified as having
      sustained a confirmed myocardial infarct. DESIGN: An inclusive historical cohort
      of patients admitted with a suspected heart attack. Patients were recoded from
      raw clinical data (collected at the index admission) to the epidemiological
      definitions of myocardial infarction used by the Nottingham heart attack register
      (NHAR), the World Health Organization (MONICA), and the UK heart attack study.
      SETTING: Single health district. PATIENTS: The NHAR identified all patients
      admitted in 1992 with suspected myocardial infarction. OUTCOME MEASURES: Survival
      at 30 days and four year postdischarge. RESULTS: 2739 patients were identified,
      of whom 90% survived to discharge. Recoding increased the numbers of patients
      defined as having confirmed myocardial infarction from 26% under the original
      NHAR classification to 69%, depending on the classification system used. In
      confirmed myocardial infarction, subsequent 30 day survival from admission varied
      from 77-86% depending on the classification system; four year survival after
      discharge was not affected. The distribution of important prognostic variables
      differed significantly between groups of patients with confirmed myocardial
      infarction defined by different systems. Patients with suspected but unconfirmed
      myocardial infarction under all classification systems had a worse postdischarge
      mortality. CONCLUSIONS: The classification system used had a substantial effect
      on the numbers of patients identified as having had a myocardial infarct, and on
      the 30 day survival. There were significant numbers of patients with more
      atypical presentations, not labelled as myocardial infarction, who did badly
      following discharge. More research is needed on these patients.

PMID- 12231587
TI  - Coronary thrombus in a 23 year old anabolic steroid user.

PMID- 12231588
TI  - Myocardial infarction redefined: the new ACC/ESC definition, based on cardiac
      troponin, increases the apparent incidence of infarction.
AB  - OBJECTIVES: To investigate the impact of the redefinition of the diagnostic
      criteria for myocardial infarction on its apparent incidence in a non-selected
      and representative series of patients admitted with acute chest pain. DESIGN:
      Single centre prospective study. SETTING: Medical assessment unit and cardiology
      wards of an inner city university hospital. PATIENTS: 80 consecutive patients
      aged over 25 years admitted with suspected ischaemic acute chest pain (excluding
      those where the ECG indicated definite myocardial infarction). INTERVENTIONS:
      Measurement of concentrations of conventional cardiac biomarkers (creatine kinase
      and its MB isoenzyme, CK-MB) and concentrations of the highly specific diagnostic
      indicator of myocardial damage, cardiac troponin I (cTnI) 12-24 hours after the
      onset of acute chest pain. MAIN OUTCOME MEASURES: Frequency of myocardial
      infarction as assessed by conventional diagnostic criteria (creatine kinase and
      CK-MB) plus clinical symptoms of infarction, versus frequency of infarction based
      on high sensitivity troponin assays. RESULTS: Among patients with acute coronary
      syndromes but non-diagnostic ECG changes, 40% (32/80) fulfilled the new criteria
      for myocardial infarction using high sensitivity cTnI measurement, compared with
      29% (23/80) using the conventional diagnostic criteria for myocardial infarction.
      CONCLUSIONS: The implications of the redefinition of myocardial infarction on
      patients, their care, and the use of health care resources are substantial.

PMID- 12231589
TI  - T lymphocyte infiltration in non-rheumatic aortic stenosis: a comparative
      descriptive study between tricuspid and bicuspid aortic valves.
AB  - BACKGROUND: The two most common causes of aortic stenosis are primary
      "degenerative" calcification of tricuspid aortic valves and secondary
      calcification of congenital bicuspid valves. T lymphocyte infiltration occurs in
      stenotic tricuspid aortic valves, indicating an inflammatory component, but it
      has not been shown whether it also occurs in stenotic bicuspid valves. OBJECTIVE:
      To compare non-rheumatic tricuspid and bicuspid stenotic aortic valves for the
      presence and distribution of T lymphocytes. SETTING: University hospital.
      PATIENTS AND DESIGN: Valve specimens were obtained from 29 patients (15 women, 14
      men, mean age 69 years (range 52-81 years)), referred to the hospital for aortic
      valve replacement because of symptomatic aortic valve stenosis. There were 17
      tricuspid valves (from 10 women and seven men, mean age 71 years) and 12 bicuspid
      valves (from five women and seven men, mean age 67 years). To identify
      mononuclear inflammatory cells, sections were stained with antibodies for CD3
      (pan-T cell antigen, Dako 1:400) and then graded histologically according to the
      degree of T cell infiltrate. RESULTS: T lymphocyte infiltration was present in
      both tricuspid and bicuspid stenotic aortic valves, without any significant
      differences in extent or localisation. CONCLUSIONS: Stenotic bicuspid aortic
      valves show the same degree of T lymphocyte infiltration as degenerative
      tricuspid aortic valves. Inflammation needs to be considered in the pathogenesis
      of acquired aortic stenosis, irrespective of the primary valve anomaly.

PMID- 12231590
TI  - Improved prognosis of patients presenting with clinical markers of spontaneous
      reperfusion during acute myocardial infarction.
AB  - OBJECTIVE: To describe the clinical features, management, and prognosis of
      patients presenting with clinical markers of spontaneous reperfusion (SR) during
      acute myocardial infarction (AMI). DESIGN: Cohort study. SETTING: National
      registry of 26 coronary care units. PATIENTS: 2382 consecutive patients with AMI.
      MAIN OUTCOME MEASURES: Patient characteristics, management, and mortality.
      RESULTS: The incidence of SR was 4% of patients (n = 98) compared with
      thrombolytic treatment (n = 1163, 49%), primary angioplasty (n = 102, 4%), and
      non-reperfusion (n = 1019, 43%). SR patients were more likely to develop less or
      no myocardial damage as indicated by a higher percentage of non-Q wave AMI (58% v
      32%, 47%, and 44%, respectively, p < 0.0001), aborted AMI (25% v 9%, 8%, and 12%,
      p < 0.001), and lower peak creatine kinase (503 v 1384, 1519, and 751 IU, p <
      0.0001). SR patients, however, were more likely to develop recurrent ischaemic
      events (35% v 17%, 12%, and 16%, respectively; p < 0.001) and subsequently were
      more likely to be referred to coronary angiography (67%), angioplasty (41%), or
      bypass surgery (16%, p < 0.001). Mortality at 30 days (1% v 8%, 7%, and 13%,
      respectively, p < 0.0001) and one year (6% v 11%, 12%, and 19%, p < 0.0001) was
      significantly lower for SR patients than for the other subgroups. By multivariate
      analysis, SR remained a strong determinant of 30 day survival (odds ratio (OR)
      0.16, 95% confidence interval (CI) 0.01 to 0.74). At one year, the association
      between SR and survival decreased (OR 0.49, 95% CI 0.18 to 1.13). CONCLUSIONS:
      Clinical markers of SR are associated with greater myocardial salvage and
      favourable prognosis. The vulnerability of SR patients to recurrent ischaemic
      events suggests that they need close surveillance and may benefit from early
      intervention.

PMID- 12231591
TI  - Management and outcome of patients with atrial fibrillation during acute
      myocardial infarction: the GUSTO-III experience. Global use of strategies to open
      occluded coronary arteries.
AB  - OBJECTIVE: To investigate the use of antiarrhythmic agents and electrical
      cardioversion in the management of patients with atrial fibrillation complicating
      acute myocardial infarction, and their relation to 30 day and one year mortality.
      DESIGN: Prospective study of 1138 patients with atrial fibrillation from the
      GUSTO-III trial. INTERVENTIONS: Of the 1138 study patients, 317 (28%) received
      antiarrhythmic treatment, including class I antiarrhythmic agents (12%), sotalol
      (5%), and amiodarone (15%); electrical cardioversion was attempted in 116 (10%).
      RESULTS: Sinus rhythm was restored in 72% of patients receiving class I
      antiarrhythmic agents, 67% of those receiving sotalol, 79% of those receiving
      amiodarone, and 64% of those having electrical cardioversion. After adjusting for
      baseline characteristics and complications occurring before the onset of atrial
      fibrillation, there was no difference among the treatment groups in the incidence
      of sinus rhythm at the time of discharge or before deterioration to hospital
      death. However, the use of class I antiarrhythmic drugs or sotalol was associated
      with a lower unadjusted 30 day and one year mortality. After adjustment for
      baseline factors and pre-atrial fibrillation complications, the odds ratios for
      30 day and one year mortality were 0.42 (95% confidence interval (CI) 0.19 to
      0.89) and 0.58 (95% CI 0.33 to 1.04) with class I agents, and 0.31 (95% CI 0.07
      to 1.32) and 0.31 (95% CI 0.09 to 1.02) with sotalol. In contrast, there was no
      association between the use of amiodarone or electrical cardioversion and 30 day
      or one year mortality. CONCLUSIONS: There was a strong trend towards lower
      mortality associated with the use of class I antiarrhythmic agents or sotalol in
      managing patients with atrial fibrillation after acute myocardial infarction.
      Randomised trials are indicated.

PMID- 12231593
TI  - Role of echocardiography in the evaluation of syncope: a prospective study.
AB  - OBJECTIVE: To study the role of echocardiography in the stepwise evaluation of
      syncope. DESIGN: A prospective observational study with an 18 month follow up.
      SETTING: University teaching hospital providing primary and tertiary care.
      SUBJECTS: 650 consecutive patients with syncope and clinical suspicion of an
      obstructive valvar lesion, or with syncope not explained by history, physical
      examination, or a 12 lead ECG, who underwent bidimensional Doppler transthoracic
      echocardiography. MAIN OUTCOME MEASURES: The causes of syncope were assigned
      using published diagnostic criteria. Echocardiography was considered diagnostic
      when confirming a suspected diagnosis, or when revealing occult cardiac disease
      explaining the syncope. RESULTS: A systolic murmur was identified in 61 of the
      650 patients (9%). Severe aortic stenosis was suspected in 20 of these and was
      confirmed by echocardiography in eight. Follow up excluded further cases of
      aortic stenosis. In patients with unexplained syncope (n = 155), routine
      echocardiography showed no abnormalities that established the cause of the
      syncope. Echocardiography was normal or non-relevant in all patients with a
      negative cardiac history and a normal ECG (n = 67). In patients with a positive
      cardiac history or an abnormal ECG (n = 88), echocardiography showed systolic
      dysfunction (left ventricular ejection fraction < or = 40%) in 24 (27%) and minor
      non-relevant findings in the remaining 64. Arrhythmias were diagnosed in 12 of
      the 24 patients with systolic dysfunction (50%), and in 12 of the 64 remaining
      patients (19%) (p < 0.01). CONCLUSIONS: Echocardiography was most useful for
      assessing the severity of the underlying cardiac disease and for risk
      stratification in patients with unexplained syncope but with a positive cardiac
      history or an abnormal ECG.

PMID- 12231594
TI  - Changes in transmural distribution of myocardial perfusion assessed by
      quantitative intravenous myocardial contrast echocardiography in humans.
AB  - OBJECTIVE: To clarify whether changes in transmural distribution of myocardial
      perfusion under significant coronary artery stenosis can be assessed by
      quantitative intravenous myocardial contrast echocardiography (MCE) in humans.
      METHODS: 31 patients underwent dipyridamole stress MCE and quantitative coronary
      angiography. Intravenous MCE was performed by continuous infusion of Levovist.
      Images were obtained from the apical four chamber view with alternating pulsing
      intervals both at rest and after dipyridamole infusion. Images were analysed
      offline by placing regions of interest over both endocardial and epicardial sides
      of the mid-septum. The background subtracted intensity versus pulsing interval
      plots were fitted to an exponential function, y = A (1 - e(-betat)), where A is
      plateau level and beta is rate of rise. RESULTS: Of the 31 patients, 16 had
      significant stenosis (> 70%) in the left anterior descending artery (group A) and
      15 did not (group B). At rest, there were no differences in the A endocardial to
      epicardial ratio (A-EER) and beta-EER between the two groups (mean (SD) 1.2 (0.6)
      v 1.2 (0.8) and 1.2 (0.7) v 1.1 (0.6), respectively, NS). During hyperaemia, beta
      EER in group A was significantly lower than that in group B (1.0 (0.5) v 1.4
      (0.5), p < 0.05) and A-EER did not differ between the two groups (1.0 (0.5) v 1.2
      (0.4), NS). CONCLUSIONS: Changes in transmural distribution of myocardial
      perfusion under significant coronary artery stenosis can be assessed by
      quantitative intravenous MCE in humans.

PMID- 12231595
TI  - Perindopril improves six minute walking distance in older patients with left
      ventricular systolic dysfunction: a randomised double blind placebo controlled
      trial.
AB  - OBJECTIVE: To evaluate the effects of the angiotensin converting enzyme inhibitor
      perindopril on six minute walking distance and quality of life in very old
      patients with left ventricular systolic dysfunction. DESIGN: Prospective, double
      blind placebo controlled trial. SETTING: Medicine for the elderly day hospital.
      PATIENTS: 66 patients (average age 81) with left ventricular systolic dysfunction
      identified by echocardiography. INTERVENTIONS: 10 weeks of treatment with
      titrated doses of perindopril or placebo. MAIN OUTCOME MEASURES: Six minute
      walking distance 10 weeks following treatment, quality of life measurements
      including the Minnesota living with heart failure questionnaire and the 36 item
      short form health survey. RESULTS: In patients with left ventricular systolic
      dysfunction, six minute walking distance was significantly increased in the
      treatment group (37.1 m) compared with the placebo group (-0.3 m, p < 0.001). The
      medication was well tolerated and there were no significant adverse events.
      CONCLUSIONS: Six minute walking distance is improved considerably by treatment
      with perindopril in older patients with heart failure caused by left ventricular
      systolic dysfunction.

PMID- 12231596
TI  - The pNNx files: re-examining a widely used heart rate variability measure.
AB  - OBJECTIVE: To re-examine the standard pNN50 heart rate variability (HRV)
      statistic by determining how other thresholds compare with the commonly adopted
      50 ms threshold in distinguishing physiological and pathological groups. DESIGN:
      Retrospective analysis of Holter monitor databases. SUBJECTS: Comparison of HRV
      data between 72 healthy subjects and 43 with congestive heart failure (CHF);
      between sleeping and waking states in the 72 healthy subjects; and between 20
      young and 20 healthy elderly subjects. MAIN OUTCOME MEASURES: Probability values
      for discriminating between groups using a family of pNN values ranging from pNN4
      to pNN100. RESULTS: For all three comparisons, pNN values substantially less than
      50 ms consistently provided better separation between groups. For the normal
      versus CHF groups, p < 10(-13) for pNN12 versus p < 10(-4) for pNN50; for the
      sleeping versus awake groups, p < 10(-21) for pNN12 versus p < 10(-10) for pNN50;
      and for the young versus elderly groups, p < 10(-6) for pNN28 versus p < 10(-4)
      for pNN50. In addition, for the subgroups of elderly healthy subjects versus
      younger patients with CHF, p < 0.007 for pNN20 versus p < 0.17 for pNN50; and for
      the subgroup of New York Heart Association functional class I-II CHF versus class
      III-IV, p < 0.04 for pNN10 versus p < 0.13 for pNN50. CONCLUSIONS: pNN50 is only
      one member of a general pNNx family of HRV statistics. Enhanced discrimination
      between a variety of normal and pathological conditions is obtained by using pNN
      thresholds as low as 20 ms or less rather than the standard 50 ms threshold.

PMID- 12231597
TI  - Carotid artery stenting in the first 100 consecutive patients: results and follow
      up.
AB  - BACKGROUND: Carotid artery stenting is now used as an alternative to surgical
      endarterectomy. The availability of cerebral protection systems has expanded the
      area of application of this procedure. OBJECTIVE: To assess the feasibility,
      safety, and immediate and late clinical outcome in patients undergoing
      percutaneous carotid interventions. METHODS: Between January 1999 and December
      2000, 100 consecutive patients with 102 carotid artery stenoses were treated (71
      men, 29 women, mean (SD) age 67 (8) years): 49 had coronary artery disease, 28
      had previous stroke or transient ischaemic attack (TIA). On the basis of the Mayo
      Clinic carotid endarterectomy risk scale, 73 patients were grade III-IV and 13
      grade VI. RESULTS: Baseline diameter stenosis was 78.8 (10)%, with a mean lesion
      length of 12.6 (5.8) mm. Angiographic success was obtained in 99 lesions (97.0%)
      with a final diameter stenosis of 2.4 (3.5)%. Procedural success was obtained in
      96 patients (96%). Selective cannulation of three carotid arteries was impossible
      owing to severe vessel tortuosity. Carotid stenting was performed in 97 of the
      treated lesions, and protection devices were used in 67 lesions. In-hospital
      complications occurred in seven patients (six TIA, one (category 1) minor
      stroke). No major stroke or death occurred. All patients were discharged from the
      hospital after an average of 2.5 days. At 12 (6.2) months of follow up restenosis
      occurred in three patients (3.4%) (one patient with carotid occlusion had TIA).
      Six patients had died: two from cerebrovascular events (5 and 11 months after the
      procedure) and four from cardiovascular causes. CONCLUSIONS: Carotid stenting
      appears feasible and safe, with few major complications. Long term follow up is
      affected by a high incidence of cardiovascular mortality.

PMID- 12231598
TI  - Improving the effectiveness of routine prenatal screening for major congenital
      heart defects.
AB  - OBJECTIVE: To evaluate the effectiveness of adding outlet views to the four
      chamber view in routine prenatal ultrasound screening for major congenital heart
      defects (CHD) as performed by trained sonographers, and to compare the procedure
      with current practice. DESIGN AND SETTING: Prospective observational study at a
      London teaching hospital. PARTICIPANTS AND METHODS: 9277 women booked at a single
      institution (80% had first trimester nuchal translucency measurement) due to have
      routine fetal cardiac screening using the four chamber and outflow tract views at
      > 18 weeks of gestation. MAIN OUTCOME MEASURE: Identification of major CHD in
      chromosomally normal and abnormal pregnancies antenatally or postnatally.
      RESULTS: There were 40 abnormalities (4.3/1000), of which 30 were chromosomally
      normal (3.3/1000). The overall antenatal detection rate was 75% (95% confidence
      interval (CI) 59% to 87%) and 70% (95% CI 51% to 85%) for euploid pregnancies.
      Abnormal cardiac views accounted for 70% of all prenatal diagnoses, 30% of which
      were made at < or = 18 weeks. The sensitivity of cardiac views during the first
      scan at > 18 weeks was 52%. Of all patients undergoing nuchal translucency
      screening, 34 had major CHD, nine with increased nuchal translucency (26.5%).
      Factors influencing the results of this screening programme were training and
      audit of operators, adequate equipment for antenatal examination, ease of access,
      and low threshold for referral to specialised fetal echocardiography. CONCLUSION:
      Adding ventricular outlet views to the four chamber assessment of the heart at
      routine fetal anomaly scans at > 18 weeks is the most effective technique to
      detect CHD prenatally. The success of such a programme depends on an
      infrastructure committed to continuous in house training of obstetric
      ultrasonographers coupled with feedback from specialised fetal cardiologists, as
      well as adequate resource allocation to obstetric hospitals involved with
      antenatal screening.

PMID- 12231599
TI  - Endocardial and epicardial steroid lead pacing in the neonatal and paediatric age
      group.
AB  - AIM: To compare the performance of steroid eluting epicardial and endocardial
      leads in infants and children requiring permanent pacing. METHODS: Evaluation of
      pacing and sensing characteristics, impedances, and longevity of 159 steroid
      eluting leads implanted in 95 children. Group A consisted of 24 children weighing
      less than 15 kg with 15 endocardial leads (five atrial, 10 ventricular) and 19
      epicardial leads (five atrial, 14 ventricular). Group B consisted of 71 children
      weighing more than 15 kg with 106 endocardial leads (56 atrial, 58 ventricular)
      and 19 epicardial leads (nine atrial, 10 ventricular). RESULTS: Group A:
      Stimulation thresholds were lower for ventricular endocardial leads at implant
      (mean (SD) 0.84 (0.54) v 1.59 (0.64) V, p < 0.014) and at two year follow up
      (ventricular 0.64 (0.24) v 1.65 (0.69) V, p < 0.003). Impedance and sensing
      thresholds did not differ significantly at implant and follow up. Group B:
      Stimulation thresholds were lower for ventricular endocardial leads at implant
      (0.72 (0.48) v 1.48 (0.58) V, p < 0.001) and at follow up (0.88 (0.46) v 1.55
      (0.96) V, p < 0.009). Impedance did not differ. Sensing thresholds were also
      better for ventricular endocardial leads at follow up (9.1 (5.2) v 14.2 (6.4) mV,
      p < 0.02). Complications requiring intervention occurred in both groups (n = 7
      for endocardial v n = 18 for epicardial leads). CONCLUSIONS: Endocardial and
      epicardial steroid eluting leads have comparable performance in the paediatric
      population.

PMID- 12231600
TI  - Thrombosis in the proximal pulmonary artery stump in a Fontan patient.

PMID- 12231601
TI  - Effect of load alterations on the effective regurgitant orifice area in chronic
      aortic regurgitation.
AB  - OBJECTIVE: To evaluate the load dependence of effective regurgitant orifice area
      (ROA) in an animal model of chronic aortic regurgitation. METHODS: Eight sheep
      were studied 10-20 weeks after the surgical creation of aortic regurgitation.
      After baseline studies, 500 ml of blood, angiotensin II, and nitroprusside were
      infused sequentially. Electromagnetic flow meters were used as reference
      standards to determine aortic regurgitation volume. The time-velocity integral
      was acquired using the continuous wave Doppler method. RESULTS: Baseline aortic
      regurgitant volume varied from 8 ml (regurgitant fraction 28%) to 29 ml (59%),
      with a mean (SD) value of 17 (8) ml; mean ROA was 0.15 (0.05) cm2. During
      angiotensin II infusion, aortic regurgitation volume (20 (8) ml) and mean
      diastolic aortoventricular pressure gradient (62 (18) mm Hg) increased by 26
      (16)% and 48 (64)%, respectively (p < 0.01 for both). ROA did not change (0.16
      (0.06) cm(2), p = 0.15). During nitroprusside infusion, aortic regurgitant volume
      (13 (7) ml, p = 0.05) and diastolic pressure gradient (25 (13) mm Hg, p < 0.05)
      decreased. ROA did not change (0.15 (0.05) cm2). When analysing 32 stages
      together, aortic regurgitant volume (r = 0.78, p < 0.01) and regurgitant fraction
      (r = 0.55, p < 0.01) correlated well with ROA. However, diastolic pressure
      gradient (r = 0.28) was not significantly correlated with ROA. CONCLUSIONS: In an
      animal model of chronic aortic regurgitation, ROA did not change with load
      alterations.

PMID- 12231602
TI  - Coronary-pulmonary artery fistulae: blood flow pattern and effect on myocardial
      perfusion.

PMID- 12231603
TI  - Coronary artery stretch versus deep injury in the development of in-stent
      neointima.
AB  - OBJECTIVE: To investigate the relative importance of stent induced arterial
      stretch and deep injury to the development of in-stent neointima. SETTING: Normal
      porcine coronary arteries METHODS: 30 BiodivYsio stents (Biocompatibles) were
      deployed at a stent to artery ratio of 1.25:1 (a moderate injury) and harvested
      at 28 days. Multiple serial cross sections were analysed morphometrically and the
      neointimal areas were correlated with the type and degree of injury. RESULTS:
      Arterial stretch occurred in 78% of struts (77% of sections) and produced
      moderate neointimal growth (neointimal area 1.93 (0.13) mm2). Deep injury
      (rupture of the internal elastic lamina) occurred in 20% of struts (23% of
      sections) and produced a 1.7-fold increase in neointimal area (3.33 (0.41) mm2)
      compared with stretch only (p = 0.0002). With even deeper injury (rupture of the
      external elastic lamina), there was a 2.6-fold increase in neointimal area (5.01
      (0.48) mm2) compared with stretch only (p = 0.02). A new injury score,
      incorporating both stretch and deep injury, correlated with neointimal area (r =
      0.60, p < 0.001). CONCLUSIONS: Stretch of the coronary artery in a stent is
      common, and a major contributor to neointima formation, even in the absence of
      deep injury. Deep injury is, however, a more potent stimulus to neointima
      formation than stretch. Greater degrees of stretch are associated with thicker
      neointima. Where neither deep injury nor stretch are seen, the stent has no
      effect upon the development of neointima.

PMID- 12231604
TI  - The terminal crest: morphological features relevant to electrophysiology.
AB  - OBJECTIVE: To investigate the detailed anatomy of the terminal crest (crista
      terminalis) and its junctional regions with the pectinate muscles and intercaval
      area to provide the yardstick for structural normality. DESIGN: 97 human necropsy
      hearts were studied from patients who were not known to have medical histories of
      atrial arrhythmias. The dimensions of the terminal crest were measured in width
      and thickness from epicardium to endocardium, at the four points known to be
      chosen as sites of ablation. RESULTS: The pectinate muscles originating from the
      crest and extending along the wall of the appendage towards the vestibule of the
      tricuspid valve had a non-uniform trabecular pattern in 80% of hearts. Fine
      structure of the terminal crest studied using light and scanning electron
      microscopy consisted of much thicker and more numerous fibrous sheaths of
      endomysium with increasing age of the patient. 36 specimens of 45 (80%) specimens
      studied by electron microscopy had a predominantly uniform longitudinal
      arrangement of myocardial fibres within the terminal crest. In contrast, in all
      specimens, the junctional areas of the terminal crest with the pectinate muscles
      and with the intercaval area had crossing and non-uniform architecture of
      myofibres. CONCLUSIONS: The normal anatomy of the muscle fibres and connective
      tissue in the junctional area of the terminal crest/pectinate muscles and
      terminal crest/intercaval bundle favours non-uniform anisotropic properties.

PMID- 12231605
TI  - Identification of a specific pattern of downregulation in expression of isoforms
      of vascular endothelial growth factor in dilated cardiomyopathy.

PMID- 12231606
TI  - Atrial flutter with 1:1 conduction.

PMID- 12231607
TI  - Intensive statin treatment improves baroreflex sensitivity: another
      cardioprotective mechanism for statins?

PMID- 12231609
TI  - Effects of perindopril on soluble intercellular adhesion molecule-1 in patients
      with congestive heart failure.

PMID- 12231611
TI  - Role of echocardiography in acute coronary syndromes.

PMID- 12231612
TI  - Sudden death in children and adolescents.

PMID- 12231613
TI  - Treatment of atrial fibrillation.

PMID- 12231614
TI  - Exercise induced ST elevation and T wave alternans associated with critical
      disease of left anterior descending coronary artery.

PMID- 12231615
TI  - Demonstration of supravalvar aortic stenosis by different cardiac imaging
      modalities in Williams syndrome.

PMID- 12231617
TI  - Acute effects of resynchronisation treatment on functional mitral regurgitation
      in dilated cardiomyopathy.

PMID- 12231619
TI  - Degrading Ci: who is Cul-pable?

PMID- 12231618
TI  - Continuous left hemidiaphragm sign revisited: a case of spontaneous
      pneumopericardium and literature review.
AB  - In pneumopericardium, a rare but potentially life threatening differential
      diagnosis of chest pain with a broad variety of causes, rapid diagnosis and
      adequate treatment are crucial. In upright posteroanterior chest radiography, the
      apical limit of a radiolucent rim, outlining both the left ventricle and the
      right atrium, lies at the level of the pulmonary artery and ascending aorta,
      reflecting the anatomical limits of the pericardium. The band of gas surrounding
      the heart may outline the normally invisible parts of the diaphragm, producing
      the continuous left hemidiaphragm sign in an upright lateral chest radiograph. If
      haemodynamic conditions are stable, the underlying condition should be treated
      and the patient should be monitored closely. Acute haemodynamic deterioration
      should prompt rapid further investigation and cardiac tamponade must be actively
      ruled out. Spontaneous pneumopericardium in a 20 year old man is presented, and
      its pathophysiology described.

PMID- 12231620
TI  - The remarkable ubiquity of DM domain factors as regulators of sexual phenotype:
      ancestry or aptitude?

PMID- 12231621
TI  - A requirement for replication in activation of the ATR-dependent DNA damage
      checkpoint.
AB  - Using the Xenopus egg extract system, we investigated the involvement of DNA
      replication in activation of the DNA damage checkpoint. We show here that DNA
      damage slows replication in a checkpoint-independent manner and is accompanied by
      replication-dependent recruitment of ATR and Rad1 to chromatin. We also find that
      the replication proteins RPA and Polalpha accumulate on chromatin following DNA
      damage. Finally, damage-induced Chk1 phosphorylation and checkpoint arrest are
      abrogated when replication is inhibited. These data indicate that replication is
      required for activation of the DNA damage checkpoint and suggest a unifying model
      for ATR activation by diverse lesions during S phase.

PMID- 12231622
TI  - Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is
      required for rejoining of DNA double-strand breaks.
AB  - Nonhomologous end-joining (NHEJ) is the predominant pathway that repairs DNA
      double-strand breaks (DSBs) in mammalian cells. The DNA-dependent protein kinase
      (DNA-PK), consisting of Ku and DNA-PK catalytic subunit (DNA-PKcs), is activated
      by DNA in vitro and is required for NHEJ. We report that DNA-PKcs is
      autophosphorylated at Thr2609 in vivo in a Ku-dependent manner in response to
      ionizing radiation. Phosphorylated DNA-PKcs colocalizes with both gamma-H2AX and
      53BP1 after DNA damage. Mutation of Thr2609 to Ala leads to radiation sensitivity
      and impaired DSB rejoining. These findings establish that Ku-dependent
      phosphorylation of DNA-PKcs at Thr2609 is required for the repair of DSBs by
      NHEJ.

PMID- 12231623
TI  - Nodal activity in the node governs left-right asymmetry.
AB  - Nodal is expressed at the lateral edges of the mouse node, but its function in
      this "organizer" tissue remains unknown due to the early lethality of Nodal
      mutant embryos. Here we used a genetic strategy to selectively remove Nodal
      activity from the node. Embryos lacking Nodal in the node fail to initiate
      molecular asymmetry in the left lateral plate mesoderm and exhibit multiple left
      right patterning defects. Nodal may also act as a short-range signal to establish
      a functional midline barrier. Our findings confirm that the mouse node is
      instrumental in initiating left-right axis specification and identify Nodal as
      the key morphogen regulating this process.

PMID- 12231624
TI  - Multiple regulatory changes contribute to the evolution of the Caenorhabditis lin
      48 ovo gene.
AB  - Recent work points to the importance of changes in gene expression patterns in
      species-specific differences. Here, we investigate the evolution of the nematode
      lin-48 ovo gene. lin-48 is expressed in several cells in both Caenorhabditis
      elegans and Caenorhabditis briggsae, but acts in the excretory duct cell only in
      C. elegans. We find the differences result both from alterations in the cis
      regulatory sequences and in proteins that mediate lin-48 expression. One factor
      that contributes to the species differences is the bZip protein CES-2. Our
      results indicate the accumulation of several regulatory changes affecting one
      gene can contribute to evolutionary change.

PMID- 12231625
TI  - The suppression of brain cold-stable microtubules in mice induces synaptic
      defects associated with neuroleptic-sensitive behavioral disorders.
AB  - Neurons contain abundant subsets of highly stable microtubules that resist
      depolymerizing conditions such as exposure to the cold. Stable microtubules are
      thought to be essential for neuronal development, maintenance, and function.
      Previous work has indicated an important role of the microtubule-associated
      protein STOP in the induction of microtubule cold stability. Here, we developed
      STOP null mice. These mice were devoid of cold-stable microtubules. In contrast
      to our expectations, STOP-/- mice had no detectable defects in brain anatomy but
      showed synaptic defects, with depleted synaptic vesicle pools and impaired
      synaptic plasticity, associated with severe behavioral disorders. A survey of the
      effects of psychotropic drugs on STOP-/- mice behavior showed a remarkable and
      specific effect of long-term administration of neuroleptics in alleviating these
      disorders. This study demonstrates that STOP is a major factor responsible for
      the intriguing stability properties of neuronal microtubules and is important for
      synaptic plasticity. Additionally, STOP-/- mice may yield a pertinent model for
      study of neuroleptics in illnesses such as schizophrenia, currently thought to
      result from synaptic defects.

PMID- 12231626
TI  - Specification of the mammalian cochlea is dependent on Sonic hedgehog.
AB  - Organization of the inner ear into auditory and vestibular components is
      dependent on localized patterns of gene expression within the otic vesicle.
      Surrounding tissues are known to influence compartmentalization of the otic
      vesicle, yet the participating signals remain unclear. This study identifies
      Sonic hedgehog (Shh) secreted by the notochord and/or floor plate as a primary
      regulator of auditory cell fates within the mouse inner ear. Whereas otic
      induction proceeds normally in Shh(-/-) embryos, morphogenesis of the inner ear
      is greatly perturbed by midgestation. Ventral otic derivatives including the
      cochlear duct and cochleovestibular ganglia failed to develop in the absence of
      Shh. The origin of the inner ear defects in Shh(-/-) embryos could be traced back
      to alterations in the expression of a number of genes involved in cell fate
      specification including Pax2, Otx1, Otx2, Tbx1, and Ngn1. We further show that
      several of these genes are targets of Shh signaling given their ectopic
      activation in transgenic mice that misexpress Shh in the inner ear. Taken
      together, our data support a model whereby auditory cell fates in the otic
      vesicle are established by the direct action of Shh.

PMID- 12231627
TI  - Negative regulation of STAT92E by an N-terminally truncated STAT protein derived
      from an alternative promoter site.
AB  - Previously unrecognized mRNAs originating from a dual promoter at the stat92E
      locus are described. One of these encodes a truncated protein, DeltaNSTAT92E,
      that lacks the N-terminal 133 amino acids. Antibodies detect both the full-length
      and truncated molecules early in embryogenesis (1-5 h), and mRNA detection by
      specific RT-PCR reactions accords with the protein distribution. Given that the N
      termini of mammalian STATs are known to have positive functions in
      transcriptional activation, we explored the role of DeltaNSTAT92E early in
      embryogenesis. By increasing the DeltaNSTAT92E-to-STAT92E ratio in overexpression
      and RNAi experiments, we observe phenotypes compatible with suppression of wild
      type STAT92E activity. We therefore conclude that the short form of STAT92E is a
      naturally occurring dominant-negative product that can be added to the growing
      list of negative regulators of STAT activity.

PMID- 12231628
TI  - Regulation of sex-specific differentiation and mating behavior in C. elegans by a
      new member of the DM domain transcription factor family.
AB  - Mutations in Caenorhabditis elegans gene mab-23 cause abnormal male tail
      morphology and abolish male fecundity but have no obvious effect in the
      hermaphrodite. Here we show that mab-23 encodes a DM (Doublesex/MAB-3) domain
      transcription factor necessary for specific aspects of differentiation in sex
      specific tissues of the male. mab-23 is required for the patterning of posterior
      sensory neurons in the male nervous system, sex muscle differentiation, and
      morphogenesis of the posterior hypodermis, spicules, and proctodeum. Failure of
      mab-23 mutant males to sire progeny is due primarily to defective sex muscle
      mediated turning during copulatory behavior and likely compounded by impairment
      of sperm passage through the proctodeum. In the male nervous system, mab-23
      refines ray neuron subtype distribution by restricting expression of dopaminergic
      neurotransmitter identity through interactions with the Hox gene egl-5 and a TGF
      beta-related signaling pathway. mab-23 has distinct roles and functions
      independent of mab-3, indicating different aspects of C. elegans male sexual
      differentiation are coordinated among DM domain family members. Our results
      support the hypothesis that DM domain genes derive from an ancestral male sexual
      regulator and suggest how regulation of sexual development has evolved in
      distinct ways in different phyla.

PMID- 12231630
TI  - Combinatorial control of Drosophila eye development by eyeless, homothorax, and
      teashirt.
AB  - In Drosophila, the development of the compound eye depends on the movement of a
      morphogenetic furrow (MF) from the posterior (P) to the anterior (A) of the eye
      imaginal disc. We define several subdomains along the A-P axis of the eye disc
      that express distinct combinations of transcription factors. One subdomain,
      anterior to the MF, expresses two homeobox genes, eyeless (ey) and homothorax
      (hth), and the zinc-finger gene teashirt (tsh). We provide evidence that this
      combination of transcription factors may function as a complex and that it plays
      at least two roles in eye development: it blocks the expression of later-acting
      transcription factors in the eye development cascade, and it promotes cell
      proliferation. A key step in the transition from an immature proliferative state
      to a committed state in eye development is the repression of hth by the BMP-4
      homolog Decapentaplegic (Dpp).

PMID- 12231629
TI  - Distinct protein degradation mechanisms mediated by Cul1 and Cul3 controlling Ci
      stability in Drosophila eye development.
AB  - The ubiquitin-like protein, Nedd8, covalently modifies members of the Cullin
      family. Cullins are the major components of a series of ubiquitin ligases that
      control the degradation of a broad range of proteins. We found that Nedd8
      modifies Cul1 in Drosophila. In Drosophila Nedd8 and Cul1 mutants, protein levels
      of the signal transduction effectors, Cubitus interruptus (Ci) and Armadillo
      (Arm), and the cell cycle regulator, Cyclin E (CycE), are highly accumulated,
      suggesting that the Cul1-based SCF complex requires Nedd8 modification for the
      degradation processes of Ci, Arm, and CycE in vivo. We further show that two
      distinct degradation mechanisms modulating Ci stability in the developing eye
      disc are separated by the morphogenetic furrow (MF) in which retinal
      differentiation is initiated. In cells anterior to the MF, Ci proteolytic
      processing promoted by PKA requires the activity of the Nedd8-modified Cul1-based
      SCF(Slimb) complex. In posterior cells, Ci degradation is controlled by a
      mechanism that requires the activity of Cul3, another member of the Cullin
      family. This posterior Ci degradation mechanism, which partially requires Nedd8
      modification, is activated by Hedgehog (Hh) signaling and is PKA-independent.

PMID- 12231631
TI  - Synapsis-dependent and -independent mechanisms stabilize homolog pairing during
      meiotic prophase in C. elegans.
AB  - Analysis of Caenorhabditis elegans syp-1 mutants reveals that both synapsis
      dependent and -independent mechanisms contribute to stable, productive alignment
      of homologous chromosomes during meiotic prophase. Early prophase nuclei undergo
      normal reorganization in syp-1 mutants, and chromosomes initially pair. However,
      the polarized nuclear organization characteristic of early prophase persists for
      a prolonged period, and homologs dissociate prematurely; furthermore, the
      synaptonemal complex (SC) is absent. The predicted structure of SYP-1, its
      localization at the interface between intimately paired, lengthwise-aligned
      pachytene homologs, and its kinetics of localization with chromosomes indicate
      that SYP-1 is an SC structural component. A severe reduction in crossing over
      together with evidence for accumulated recombination intermediates in syp-1
      mutants indicate that initial pairing is not sufficient for completion of
      exchange and implicates the SC in promoting crossover recombination. Persistence
      of polarized nuclear organization in syp-1 mutants suggests that SC
      polymerization may provide a motive force or signal that drives redispersal of
      chromosomes. Whereas our analysis suggests that the SC is required to stabilize
      pairing along the entire lengths of chromosomes, striking differences in peak
      pairing levels for opposite ends of chromosomes in syp-1 mutants reveal the
      existence of an additional mechanism that can promote local stabilization of
      pairing, independent of synapsis.

PMID- 12231633
TI  - Flow-dependent changes in microvascular permeability -- an important adaptive
      phenomenon.

PMID- 12231632
TI  - Proteolytic cleavage of the THR subunit during anaphase limits Drosophila
      separase function.
AB  - Sister-chromatid separation in mitosis requires proteolytic cleavage of a cohesin
      subunit. Separase, the corresponding protease, is activated at the metaphase-to
      anaphase transition. Activation involves proteolysis of an inhibitory subunit,
      securin, following ubiquitination mediated by the anaphase-promoting
      complex/cyclosome. In Drosophila, the securin PIM associates not only with
      separase (SSE), but also with an additional protein, THR. Here we show that THR
      is cleaved after the metaphase-to-anaphase transition. THR cleavage only occurs
      in functional SSE complexes and in a region that matches the separase cleavage
      site consensus. Mutations in this region abolish mitotic THR cleavage. These
      results indicate that THR is cleaved by SSE. Expression of noncleavable THR
      variants results in cold-sensitive maternal-effect lethality. This lethality can
      be suppressed by a reduction of catalytically active SSE levels, indicating that
      THR cleavage inactivates SSE complexes. THR cleavage is particularly important
      during the process of cellularization, which follows completion of the last
      syncytial mitosis of early embryogenesis, suggesting that Drosophila separase has
      other targets in addition to cohesin subunits.

PMID- 12231634
TI  - Hibernating without oxygen: physiological adaptations of the painted turtle.
AB  - Many freshwater turtles in temperate climates may experience winter periods
      trapped under ice unable to breathe, in anoxic mud, or in water depleted of O(2).
      To survive, these animals must not only retain function while anoxic, but they
      must do so for extended periods of time. Two general physiological adaptive
      responses appear to underlie this capacity for long-term survival. The first is a
      coordinated depression of metabolic processes within the cells, both the
      glycolytic pathway that produces ATP and the cellular processes, such as ion
      pumping, that consume ATP. As a result, both the rate of substrate depletion and
      the rate of lactic acid production are slowed greatly. The second is an
      exploitation of the extensive buffering capacity of the turtle's shell and
      skeleton to neutralize the large amount of lactic acid that eventually
      accumulates. Two separate shell mechanisms are involved: release of carbonate
      buffers from the shell and uptake of lactic acid into the shell where it is
      buffered and sequestered. Together, the metabolic and buffering mechanisms permit
      animals to survive for 3-4 months at 3 degrees C with no O(2) and with
      circulating lactate levels of 150 mmol l(-1) or more.

PMID- 12231635
TI  - Age-dependent synapse withdrawal at axotomised neuromuscular junctions in Wld(s)
      mutant and Ube4b/Nmnat transgenic mice.
AB  - Axons in Wld(S) mutant mice are protected from Wallerian degeneration by
      overexpression of a chimeric Ube4b/Nmnat (Wld) gene. Expression of Wld protein
      was independent of age in these mice. However we identified two distinct
      neuromuscular synaptic responses to axotomy. In young adult Wld(s) mice, axotomy
      induced progressive, asynchronous synapse withdrawal from motor endplates,
      strongly resembling neonatal synapse elimination. Thus, five days after axotomy,
      50-90 % of endplates were still partially or fully occupied and expressed
      endplate potentials (EPPs). By 10 days, fewer than 20 % of endplates still showed
      evidence of synaptic activity. Recordings from partially occupied junctions
      indicated a progressive decrease in quantal content in inverse proportion to
      endplate occupancy. In Wld(s) mice aged > 7 months, axons were still protected
      from axotomy but synapses degenerated rapidly, in wild-type fashion: within three
      days less than 5 % of endplates contained vestiges of nerve terminals. The
      axotomy-induced synaptic withdrawal phenotype decayed with a time constant of
      approximately 30 days. Regenerated synapses in mature Wld(s) mice recapitulated
      the juvenile phenotype. Within 4-6 days of axotomy 30-50 % of regenerated nerve
      terminals still occupied motor endplates. Age-dependent synapse withdrawal was
      also seen in transgenic mice expressing the Wld gene. Co-expression of Wld
      protein and cyan fluorescent protein (CFP) in axons and neuromuscular synapses
      did not interfere with the protection from axotomy conferred by the Wld gene.
      Thus, Wld expression unmasks age-dependent, compartmentally organised programmes
      of synapse withdrawal and degeneration.

PMID- 12231636
TI  - Effects of thyroxine on myosin isoform expression and mechanical properties in
      guinea-pig smooth muscle.
AB  - Information on the effects of thyroid hormone on smooth muscle contractile
      protein expression and mechanical properties is sparse. We have addressed the
      following questions. (1) Can thyroxine hormone alter myosin isoform composition
      in smooth muscle? (2) Can a change in myosin isoform composition lead to altered
      mechanical properties in smooth muscle? (3) Are alterations, if occurring, equal
      in fast and slow smooth muscle types? Guinea-pigs were treated with thyroxine
      (T(4)) for 12 days. Control animals were given physiological saline solution.
      Maximal unloaded shortening velocity (V(max)) was measured in chemically skinned,
      maximally activated muscle preparations from the aorta and the taenia coli.
      V(max) increased following thyroxine treatment, by approximately 20 % in the
      taenia coli. In the aorta, no significant increase in V(max) could be detected.
      The sensitivity of isometric force to inorganic phosphate (P(i)) was increased in
      the taenia coli following thyroxine treatment. The expression of mRNA (determined
      with RT-PCR) for the myosin heavy chain with the seven amino acid insert
      increased by approximately 70 % in the aorta and about 25 % in the taenia coli
      following thyroxine treatment. Western blot analysis showed an increase in the
      inserted myosin heavy chain form in the taenia coli. Expression of mRNA for the
      myosin essential light chains and the corresponding proteins did not change
      significantly in either muscle type. No alterations in non-muscle myosin heavy
      chain isoforms could be detected after thyroxine treatment. In conclusion,
      thyroxine treatment alters the isoform composition of myosin in fast and slow
      smooth muscles in vivo. This change is sufficient to increase shortening velocity
      and sensitivity of isometric force to P(i) in the fast, but not in the slow,
      smooth muscle type.

PMID- 12231637
TI  - Role for cAMP and protein phosphatase in the presynaptic expression of mouse
      hippocampal mossy fibre depotentiation.
AB  - Long-term potentiation (LTP) at the hippocampal mossy fibre-CA3 synapses can be
      reversed (depotentiated) by long trains of low-frequency stimulation (LFS). In
      the present study, we showed that this depotentiation is triggered by a
      presynaptic group II metabotropic glutamate receptor (mGluR), which reduces
      cytosolic cAMP level, leading to a reversal of cellular processes responsible for
      mossy fibre LTP expression. Furthermore, we found that both the presynaptic
      activity-induced elevation of Ca(2+) and the activation of protein phosphatase
      (PP) activity are required for the induction of depotentiation. Thus, we conclude
      that mossy fibre depotentiation is expressed presynaptically through the
      activation of both presynaptic mGluR- and PP-coupled signalling cascades, and
      that the bidirectional long-term plasticity at the mossy fibre-CA3 synapses is
      likely to be regulated by presynaptic Ca(2+)-dependent processes.

PMID- 12231638
TI  - A model of atropine-resistant theta oscillations in rat hippocampal area CA1.
AB  - Theta frequency oscillations are a predominant feature of rhythmic activity in
      the hippocampus. We demonstrate that hippocampal area CA1 generates atropine
      resistant theta population oscillations in response to metabotropic glutamate
      receptor activation under conditions of reduced AMPA receptor activation. This
      activity occurred in the absence of inputs from area CA3 and extra-ammonic areas.
      Field theta oscillations were co-expressed with pyramidal distal apical dendritic
      burst spiking and were temporally related to trains of IPSPs with slow kinetics.
      Pyramidal somatic responses showed theta oscillations consisted of compound
      inhibitory synaptic potentials with initial IPSPs with slow kinetics followed by
      trains of smaller, faster IPSPs. Pharmacological modulation of IPSPs altered the
      theta oscillation suggesting an inhibitory network origin. Somatic IPSPs,
      dendritic burst firing and stratum pyramidale interneuron activity were all
      temporally correlated with spiking in stratum oriens interneurons demonstrating
      intrinsic theta-frequency oscillations. Disruption of spiking in these
      interneurons was accompanied by a loss of both field theta and theta frequency
      IPSP trains. We suggest that population theta oscillations can be generated as a
      consequence of intrinsic theta frequency spiking activity in a subset of stratum
      oriens interneurons controlling electrogenesis in pyramidal cell apical
      dendrites.

PMID- 12231639
TI  - Different metabotropic glutamate receptors play opposite roles in synaptic
      plasticity of the rat medial vestibular nuclei.
AB  - In the medial vestibular nuclei (MVN) of rat brainstem slices, the role of group
      II and III metabotropic glutamate receptors (mGluRs) and of the subtypes of group
      I mGluRs: mGluR1, mGluR5, was investigated in basal synaptic transmission and in
      the induction and maintenance of long-term potentiation (LTP). We used selective
      antagonists and agonists for mGluRs and we analysed the field potentials evoked
      by vestibular afferent stimulation before and after high-frequency stimulation
      (HFS) to induce LTP. The group II and III mGluR antagonist, (R,S)-alpha-2-methyl
      4sulphonophenylglycine (MSPG), induced LTP per se and caused a reduction of the
      paired-pulse facilitation (PPF) ratio indicating an enhancement of glutamate
      release. This suggests that group II and III mGluRs are activated under basal
      conditions to limit glutamate release. Both the group II and III mGluR selective
      antagonists, 2S-2-amino-2-(1S,2S-2-carboxycycloprop-1-yl)-3-(xanth-9
      yl)propanoate (LY341495) and (R,S)-alpha-methylserine-O-phosphate (MSOP), induced
      LTP, and the selective agonists, (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate
      (APDC) and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) depressed the field
      potentials and prevented HFS-LTP, with a prevailing contribution of group II
      mGluRs over that of group III mGluRs. The mGluR1 antagonist, 7
      (hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) prevented
      the full development and maintenance of HFS-LTP. By contrast, the mGluR5
      antagonist, 2-methyl-6-phenylethynylpyridine (MPEP) induced LTP per se, which was
      impeded by CPCCOEt, and it had no effect on LTP once induced by HFS. The PPF
      analysis showed an enhancement of glutamate release during MPEP potentiation. The
      group I mGluR agonist, (R,S)-3,5-dihydroxyphenylglycine (DHPG) induced LTP per
      se, which was blocked by CPCCOEt. By contrast the mGluR5 agonist, (R,S)-2-chloro
      5-hydroxypheylglycine (CHPG) prevented LTP elicited by HFS and DHPG as well. In
      conclusion vestibular LTP is inhibited by group II and III mGluRs during the
      early induction phase while it is facilitated by mGluR1 for achieving its full
      expression and consolidation. An additional inhibitory control is exerted by
      mGluR5 at the level of this facilitatory phase.

PMID- 12231640
TI  - Role of presynaptic muscarinic and GABA(B) receptors in spinal glutamate release
      and cholinergic analgesia in rats.
AB  - Spinally administered muscarinic receptor agonists or acetylcholinesterase
      inhibitors can produce effective pain relief. However, the analgesic mechanisms
      and the site of actions of cholinergic agents in the spinal cord are not fully
      understood. In this study, we investigated the mechanisms underlying cholinergic
      presynaptic regulation of glutamate release onto spinal dorsal horn neurons. The
      role of spinal GABA(B) receptors in the antinociceptive action of muscarine was
      also determined. Whole-cell voltage-clamp recordings were performed on visualized
      dorsal horn neurons in the lamina II in the spinal cord slice preparation of
      rats. The miniature excitatory postsynaptic currents (mEPSCs) and miniature
      inhibitory postsynaptic currents (mIPSCs) were recorded in the presence of
      tetrodotoxin. The evoked EPSCs (eEPSCs) were obtained by electrical stimulation
      of the dorsal root entry zone or the attached dorsal root. Nociception in rats
      was measured using a radiant heat stimulus and the effect of intrathecal
      administration of drugs tested. Acetylcholine (10-100 microM) reduced the
      amplitude of monosynaptic eEPSCs in a concentration-dependent manner.
      Acetylcholine also significantly decreased the frequency of non-NMDA receptor
      mediated mEPSCs, which was antagonized by atropine but not mecamylamine. The
      frequency of GABA(A) receptor-mediated mIPSCs was significantly increased by
      acetylcholine and this excitatory effect was abolished by atropine. Existence of
      presynaptic M(2) muscarinic receptors in the spinal dorsal horn was further
      demonstrated by immunocytochemistry staining and dorsal rhizotomy. CGP55845, a
      GABA(B) receptor antagonist, significantly attenuated the inhibitory effect of
      acetylcholine on the frequency of mEPSCs and the amplitude of monosynaptic eEPSCs
      in lamina II neurons. Furthermore, the antinociceptive action produced by
      intrathecal muscarine was significantly reduced by CGP55845 pretreatment in rats.
      Therefore, data from this integrated study provide new information that
      acetylcholine inhibits the glutamatergic synaptic input to lamina II neurons
      through presynaptic muscarinic receptors. Inhibition of glutamate release onto
      lamina II neurons by presynaptic muscarinic and GABA(B) heteroreceptors in the
      spinal cord probably contributes to the antinociceptive action of cholinergic
      agents.

PMID- 12231641
TI  - Contribution of a calcium-activated non-specific conductance to NMDA receptor
      mediated synaptic potentials in granule cells of the frog olfactory bulb.
AB  - We studied granule cells (GCs) in the intact frog olfactory bulb (OB) by
      combining whole-cell recordings and functional two-photon Ca(2+) imaging in an in
      vitro nose-brain preparation. GCs are local interneurones that shape OB output
      via distributed dendrodendritic inhibition of OB projection neurones, the mitral
      tufted cells (MTCs). In contrast to MTCs, GCs exhibited a Ca(2+)-activated non
      specific cation conductance (I(CAN)) that could be evoked through strong synaptic
      stimulation or suprathreshold current injection. Photolysis of the caged Ca(2+)
      chelator o-nitrophenol-EGTA resulted in activation of an inward current with a
      reversal potential within the range -20 to +10 mV. I(CAN) in GCs was suppressed
      by the intracellular Ca(2+) chelator BAPTA (0.5-5.0 mM), but not by EGTA (up to 5
      mM). The current persisted in whole-cell recordings for up to 1.5 h post
      breakthrough, was observed during perforated-patch recordings and was independent
      of ionotropic glutamate and GABA(A) receptor activity. In current-clamp mode, GC
      responses to synaptic stimulation consisted of an initial AMPA-mediated
      conductance followed by a late-phase APV-sensitive plateau (100-500 ms). BAPTA
      mediated suppression of I(CAN) resulted in a selective reduction of the late
      component of the evoked synaptic potential, consistent with a positive feedback
      relationship between NMDA receptor (NMDAR) current and I(CAN). I(CAN) requires
      Ca(2+) influx either through voltage-gated Ca(2+) channels or possibly NMDARs,
      both of which have a high threshold for activation in GCs, predicting a
      functional role for this current in the selective enhancement of strong synaptic
      inputs to GCs.

PMID- 12231642
TI  - c-Fos expression in ouabain-treated vascular smooth muscle cells from rat aorta:
      evidence for an intracellular-sodium-mediated, calcium-independent mechanism.
AB  - In this study, we examined the effect of Na(+)-K(+) pump inhibition on the
      expression of early response genes in vascular smooth muscle cells (VSMC) as
      possible intermediates of the massive RNA synthesis and protection against
      apoptosis seen in ouabain-treated VSMC in our previous experiments. Incubation of
      VSMC with ouabain resulted in rapid induction of c-Fos protein expression with an
      approximately sixfold elevation after 2 h of incubation. c-Jun expression was
      increased by approximately fourfold after 12 h, whereas expression of activating
      transcription factor 2, cAMP/Ca(2+) response element binding protein (CREB)-1 and
      c-Myc was not altered. Markedly augmented c-Fos expression was also observed
      under Na(+)-K(+) pump inhibition in potassium-depleted medium. Na(+)-K(+) pump
      inhibition triggered c-Fos expression via elevation of the [Na(+)](i)/[K(+)](i)
      ratio. This conclusion follows from experiments showing the lack of effect of
      ouabain on c-Fos expression in high-potassium-low-sodium medium and from the
      comparison of dose responses of Na(+)-K(+) pump activity, [Na(+)](i) and
      [K(+)](i) content and c-Fos expression to ouabain. A fourfold increment of c-Fos
      mRNA was revealed 30 min following addition of ouabain to the incubation medium.
      At this time point, treatment with ouabain resulted in an approximately fourfold
      elevation of [Na(+)](i) but did not affect [K(+)](i). Augmented c-Fos expression
      was also observed under VSMC depolarization in high-potassium medium. Increments
      in both c-Fos expression and (45)Ca uptake in depolarized VSMC were abolished
      under inhibition of L-type Ca(2+) channels with 0.1 microM nicardipine. Ouabain
      did not affect the free [Ca(2+)](i) or the content of exchangeable [Ca(2+)](i).
      Ouabain-induced c-Fos expression was also insensitive to the presence of
      nicardipine and [Ca(2+)](o), as well as chelators of [Ca(2+)](o) (EGTA) and
      [Ca(2+)](i) (BAPTA). The effect of ouabain and serum on c-Fos expression was
      additive. In contrast to serum, however, ouabain failed to activate the Elk-1,
      serum response factor, CREB and activator protein-1 transcription factors
      identified within the c-Fos promoter. These results suggest that Na(+)-K(+) pump
      inhibition triggers c-Fos expression via [Na(+)](i)-sensitive [Ca(2+)](i)
      independent transcription factor(s) distinct from factors interacting with known
      response elements of this gene promoter.

PMID- 12231643
TI  - Thermoregulatory control of sympathetic fibres supplying the rat's tail.
AB  - We investigated the thermoregulatory responses of sympathetic fibres supplying
      the tail in urethane-anaesthetised rats. When skin and rectal temperatures were
      kept above 39 degrees C, tail sympathetic fibre activity was low or absent. When
      the trunk skin was cooled episodically by 2-7 degrees C by a water jacket, tail
      sympathetic activity increased in a graded fashion below a threshold skin
      temperature of 37.8 +/- 0.6 degrees C, whether or not core (rectal) temperature
      changed. Repeated cooling episodes lowered body core temperature by 1.3-3.1
      degrees C, and this independently activated tail sympathetic fibre activity, in a
      graded fashion, below a threshold rectal temperature of 38.4 +/- 0.2 degrees C.
      Tail blood flow showed corresponding graded vasoconstrictor responses to skin and
      core cooling, albeit over a limited range. Tail sympathetic activity was more
      sensitive to core than to trunk skin cooling by a factor that varied widely (24
      fold) between animals. Combined skin and core cooling gave additive or
      facilitatory responses near threshold but occlusive interactions with stronger
      stimuli. Unilateral warming of the preoptic area reversibly inhibited tail
      sympathetic activity. This was true for activity generated by either skin or core
      cooling. Single tail sympathetic units behaved homogeneously. Their sensitivity
      to trunk skin cooling was 0.3 +/- 0.08 spikes s(-1) degrees C(-1) and to core
      cooling was 2.2 +/- 0.5 spikes s(-1) degrees C(-1). Their maximum sustained
      firing rate in the cold was 1.82 +/- 0.35 spikes s(-1).

PMID- 12231644
TI  - The relationship between intracellular [Ca(2+)] and Ca(2+) wave characteristics
      in permeabilised cardiomyocytes from the rabbit.
AB  - Spontaneous sarcoplasmic reticulum (SR) Ca(2+) release and propagated
      intracellular Ca(2+) waves are a consequence of cellular Ca(2+) overload in
      cardiomyocytes. We examined the relationship between average intracellular
      [Ca(2+)] and Ca(2+) wave characteristics. The amplitude, time course and
      propagation velocity of Ca(2+) waves were measured using line-scan confocal
      imaging of beta-escin-permeabilised cardiomyocytes perfused with 10 microM Fluo-3
      or Fluo-5F. Spontaneous Ca(2+) waves were evident at cellular [Ca(2+)] > 200 nM.
      Peak [Ca(2+)] during a wave was 2.0-2.2 microM; the minimum [Ca(2+)] between
      waves was 120-160 nM; wave frequency was approximately 0.1 Hz. Raising mean
      cellular [Ca(2+)] caused increases in all three parameters, particularly Ca(2+)
      wave frequency. Increases in the rate of SR Ca(2+) release and Ca(2+) uptake were
      observed at higher cellular [Ca(2+)], indicating calcium-sensitive regulation of
      these processes. At extracellular [Ca(2+)] > 2 microM, the mean [Ca(2+)] inside
      the permeabilised cell did not increase above 2 microM. This extracellular
      intracellular Ca(2+) gradient could be maintained for periods of up to 5 min
      before the cardiomyocyte developed a sustained and irreversible hypercontraction.
      Inclusion of mitochondrial inhibitors (2 microM carbonyl cyanide m
      chlorophenylhydrazone and 2 microM oligomycin) while perfusing with > 2 microM
      Ca(2+) abolished the extracellular-intracellular Ca(2+) gradient through the
      generation of Ca(2+) waves with a higher peak [Ca(2+)] compared to control
      conditions. Under these conditions, cardiomyocytes rapidly (< 2 min) developed a
      sustained and irreversible contraction. These results suggest that mitochondrial
      Ca(2+) uptake acts to delay an increase in [Ca(2+)] by blunting the peak of the
      Ca(2+) wave.

PMID- 12231645
TI  - Loss of enteric motor neurotransmission in the gastric fundus of Sl/Sl(d) mice.
AB  - Studies of W/W(V) mice, which lack intramuscular interstitial cells of Cajal (IC
      IM), have suggested that IC-IM act as mediators of enteric motor
      neurotransmission in the gastrointestinal tract. We have studied Sl/Sl(d) mice,
      which lack the ability to make membrane-bound stem cell factor, to determine the
      consequences of inappropriate stem cell factor expression on IC-IM populations
      and on enteric motor neurotransmission. IC-IM were found within the circular and
      longitudinal muscles of the gastric fundus of wild-type mice. IC-IM were
      intimately associated with motor nerve terminals and nerve varicosities formed
      synaptic structures with these cells. IC-IM were also connected with neighbouring
      smooth muscle cells via gap junctions. Immunohistochemistry and electron
      microscopy showed that IC-IM were absent from fundus muscles of Sl/Sl(d) mice,
      but the density of excitatory and inhibitory nerves was not significantly
      different than in wild-type muscles. Loss of IC-IM was associated with decreased
      membrane noise (unitary potentials) and significant reductions in post-junctional
      excitatory and inhibitory enteric nerve responses. Reductions in neural responses
      were not due to defects in smooth muscle cells as responses to exogenous ACh and
      K(+)-induced depolarization were normal in Sl/Sl(d) mice. Responses to neurally
      released ACh were revealed in Sl/Sl(d) mice by inhibiting ACh breakdown with the
      acetylcholinesterase inhibitor neostigmine. Inhibitory nerve stimulation elicited
      inhibitory junction potentials (IJPs) and relaxations in wild-type mice. IJPs
      were reduced in amplitude and relaxation responses were absent in Sl/Sl(d) mice.
      These observations suggest that membrane-bound stem cell factor is essential for
      development of IC-IM and that the close, synaptic-like relationship between nerve
      terminals and IC-IM may be the primary site of innervation by enteric motor
      neurons in gastric muscles.

PMID- 12231646
TI  - Mechanisms underlying the frequency dependence of contraction and [Ca(2+)](i)
      transients in mouse ventricular myocytes.
AB  - In most mammalian species force of contraction of cardiac muscle increases with
      increasing rate of stimulation, i.e. a positive force-frequency relationship. In
      single mouse ventricular cells, both positive and negative relationships have
      been described and little is known about the underlying mechanisms. We studied
      enzymatically isolated single ventricular mouse myocytes, at 30 degrees C. During
      field stimulation, amplitude of unloaded cell shortening increased with
      increasing frequency of stimulation (0.04 +/- 0.01 Delta L/L(0) at 1 Hz to 0.07
      +/- 0.01 Delta L/L(0) at 4 Hz, n = 12, P < 0.05). During whole cell voltage clamp
      with 50 microM [K5-fluo-3](pip), both peak and baseline [Ca(2+)](i) increased at
      higher stimulation frequencies, but the net Delta[Ca(2+)](i) increased only
      modestly from 1.59 +/- 0.08 Delta F/F(0) at 1 Hz, to 1.71 +/- 0.11 Delta F/F(0)
      at 4 Hz (n = 17, P < 0.05). When a 1 s pause was interposed during stimulation at
      2 and 4 Hz, [Ca(2+)](i) transients were significantly larger (at 4 Hz, peak
      F/F(0) increased by 78 +/- 2 %, n = 5). SR Ca(2+) content assessed during
      caffeine application, significantly increased from 91 +/- 24 micromol l(-1) at 1
      Hz to 173 +/- 20 micromol l(-1) at 4 Hz (n = 5, P < 0.05). Peak I(Ca,L) decreased
      at higher frequencies (by 28 +/- 6 % at 2 Hz, and 45 +/- 8 % at 4 Hz), due to
      slow recovery from inactivation. This loss of I(Ca,L) resulted in reduced
      fractional release. Thus, in mouse ventricular myocytes the [Ca(2+)](i)-frequency
      response depends on a balance between the increase in SR content and the loss of
      trigger I(Ca,L). Small changes in this balance may contribute to variability in
      frequency-dependent behaviour. In addition, there may be a regulation of the
      contractile response downstream of [Ca(2+)](i).

PMID- 12231647
TI  - The scotopic threshold response of the dark-adapted electroretinogram of the
      mouse.
AB  - The most sensitive response in the dark-adapted electroretinogram (ERG), the
      scotopic threshold response (STR) which originates from the proximal retina, has
      been identified in several mammals including humans, but previously not in the
      mouse. The current study established the presence and assessed the nature of the
      mouse STR. ERGs were recorded from adult wild-type C57/BL6 mice anaesthetized
      with ketamine (70 mg kg(-1)) and xylazine (7 mg kg(-1)). Recordings were between
      DTL fibres placed under contact lenses on the two eyes. Monocular test stimuli
      were brief flashes (lambda(max) 462 nm; -6.1 to +1.8 log scotopic Troland
      seconds(sc td s)) under fully dark-adapted conditions and in the presence of
      steady adapting backgrounds (-3.2 to -1.7 log sc td). For the weakest test
      stimuli, ERGs consisted of a slow negative potential maximal approximately 200 ms
      after the flash, with a small positive potential preceding it. The negative wave
      resembled the STR of other species. As intensity was increased, the negative
      potential saturated but the positive potential (maximal approximately 110 ms)
      continued to grow as the b-wave. For stimuli that saturated the b-wave, the a
      wave emerged. For stimulus strengths up to those at which the a-wave emerged, ERG
      amplitudes measured at fixed times after the flash (110 and 200 ms) were fitted
      with a model assuming an initially linear rise of response amplitude with
      intensity, followed by saturation of five components of declining sensitivity: a
      negative STR (nSTR), a positive STR (pSTR), a positive scotopic response (pSR),
      PII (the bipolar cell component) and PIII (the photoreceptor component). The nSTR
      and pSTR were approximately 3 times more sensitive than the pSR, which was
      approximately 7 times more sensitive than PII. The sensitive positive components
      dominated the b-wave up to > 5 % of its saturated amplitude. Pharmacological
      agents that suppress proximal retinal activity (e.g. GABA) minimized the pSTR,
      nSTR and pSR, essentially isolating PII which rose linearly with intensity before
      showing hyperbolic saturation. The nSTR, pSTR and pSR were desensitized by weaker
      backgrounds than those desensitizing PII. In conclusion, ERG components of
      proximal retinal origin that are more sensitive to test flashes and adapting
      backgrounds than PII provide the 'threshold' negative and positive (b-wave)
      responses of the mouse dark-adapted ERG. These results support the use of the
      mouse ERG in studies of proximal retinal function.

PMID- 12231648
TI  - Comparative capacitative calcium entry mechanisms in canine pulmonary and renal
      arterial smooth muscle cells.
AB  - Experiments were performed to determine whether capacitative Ca(2+) entry (CCE)
      can be activated in canine pulmonary and renal arterial smooth muscle cells
      (ASMCs) and whether activation of CCE parallels the different functional
      structure of the sarcoplasmic reticulum (SR) in these two cell types. The
      cytosolic [Ca(2+)] was measured by imaging fura-2-loaded individual cells.
      Increases in the cytosolic [Ca(2+)] due to store depletion in pulmonary ASMCs
      required simultaneous depletion of both the inositol 1,4,5-trisphosphate
      (InsP(3))- and ryanodine (RY)-sensitive SR Ca(2+) stores. In contrast, the
      cytosolic [Ca(2+)] rises in renal ASMCs occurred when the SR stores were depleted
      through either the InsP(3) or RY pathways. The increase in the cytosolic [Ca(2+)]
      due to store depletion in both pulmonary and renal ASMCs was present in cells
      that were voltage clamped and was abolished when cells were perfused with a
      Ca(2+)-free bathing solution. Rapid quenching of the fura-2 signal by 100 microM
      Mn(2+) following SR store depletion indicated that extracellular Ca(2+) entry
      increased in both cell types and also verified that activation of CCE in
      pulmonary ASMCs required the simultaneous depletion of the InsP(3)- and RY
      sensitive SR Ca(2+) stores, while CCE could be activated in renal ASMCs by the
      depletion of either of the InsP(3)- or RY-sensitive SR stores. Store depletion
      Ca(2+) entry in both pulmonary and renal ASMCs was strongly inhibited by Ni(2+)
      (0.1-10 mM), slightly inhibited by Cd(2+) (200-500 microM), but was not
      significantly affected by the voltage-gated Ca(2+) channel (VGCC) blocker
      nisoldipine (10 microM). The non-selective cation channel blocker Gd(3+) (100
      microM) inhibited a portion of the Ca(2+) entry in 6 of 18 renal but not
      pulmonary ASMCs. These results provide evidence that SR Ca(2+) store depletion
      activates CCE in parallel with the organization of intracellular Ca(2+) stores in
      canine pulmonary and renal ASMCs.

PMID- 12231649
TI  - A possible dual site of action for carbon monoxide-mediated chemoexcitation in
      the rat carotid body.
AB  - High tensions of carbon monoxide (CO), relative to oxygen, were used as a tool to
      investigate the mechanism of chemotransduction. In an in vitro whole organ, rat
      carotid body preparation, CO increased sinus nerve chemoafferent discharge in the
      dark, an effect that was significantly reduced (by ca 70 %) by bright white light
      and by the removal of extracellular Ca(2+) from the superfusate or by the
      addition of either Ni(2+) (2 mM) or methoxyverapamil (100 microM). Addition of
      the P(2) purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic
      acid (50 microM) also significantly reduced the neural response to CO. In
      perforated patch, whole-cell recordings of isolated rat type I cells, CO induced
      a depolarisation of ca 11 mV and a decrease in the amplitude of an outward
      current around and above the resting membrane potential. Membrane conductance
      between -50 and -60 mV was significantly reduced by ca 40 % by CO. These effects
      were not photolabile and were present also when a 'blocking solution' containing
      TEA, 4-AP, Ni(2+) and zero extracellular Ca(2+) was used. In conventional whole
      cell recordings, CO only decreased current amplitudes above +10 mV and was
      without effect around the resting membrane potential. These data demonstrate a
      direct effect of CO upon type I cell K(+) conductances and strongly suggest an
      effect upon a background, leak conductance that requires an intracellular
      mediator. The photolabile effect of CO only upon afferent neural discharge adds
      further evidence to a dual site of action of CO with a separate action at the
      afferent nerve terminal that, additionally, requires the permissive action of the
      neurotransmitter ATP.

PMID- 12231650
TI  - Measurement of hydraulic conductivity of single perfused Rana mesenteric
      microvessels between periods of controlled shear stress.
AB  - A new method for the determination of hydraulic conductivity in individually
      perfused microvessels in vivo is described. A vessel is cannulated at both ends
      with glass micropipettes and the fluid filtration rate across the vessel wall
      measured from the velocities of red cells when the pressure in the micropipettes
      is balanced. Hydraulic conductivity measured using this double-cannulation method
      (2.6 (+/- 0.9) x 10(-7) cm s(-1) cmH(2)O(-1)) was not significantly different
      from that measured using a previously described technique in the same vessel (2.4
      (+/- 0.9) x 10(-7) cm s(-1) cmH(2)O(-1) using the Landis-Michel method). Shear
      stress on the vessel wall was controlled by changing the difference between the
      inflow and outflow pressures during periods of perfusion. The volume flow through
      the vessel, calculated from red cell velocity either in the vessel or in the
      pipette, was linearly proportional to this pressure difference. Higher flow rates
      could only be calculated from red cell velocities in the micropipette. There was
      no relationship between the imposed shear stress and intervening measurements of
      hydraulic conductivity (r = 0.029). This novel technique has advantages over the
      Landis-Michel method, which include the control of outflow resistance, the
      measurement of shear stress under conditions of controlled pressure, the
      elimination of compression damage to the vessel (since vessel occlusion is not
      necessary) and assessment of hydraulic conductivity over the same length of
      vessel throughout the experiment. The measurement of solute concentrations by
      indwelling micropipette electrodes and the collection of perfusate for analysis
      are other possibilities.

PMID- 12231651
TI  - Effects of perfusion rate on permeability of frog and rat mesenteric microvessels
      to sodium fluorescein.
AB  - The permeability, P(S), to sodium fluorescein (Stokes-Einstein radius = 0.45 nm)
      has been measured in single mesenteric capillaries of pithed frogs and
      anaesthetised rats as perfusion velocity, U, was varied over a range from 400 up
      to 2000-10,000 microm s(-1). P(S) increased linearly with U. In 20 frog
      capillaries, mean (+/- S.E.M.) P(S) (in microm s(-1)) = 9.35 (+/- 1.55)U x 10(-5)
      + 0.244 (+/- 0.0291). Similarly, in nine rat venules, mean P(S) = 1.62 (+/-
      0.385)U x 10(-4) + 0.375 (+/- 0.025). The flow-dependent component of
      permeability could be reversibly abolished in frog capillaries by superfusing
      with 100 microM noradrenaline and by superfusing rat venules with the nitric
      oxide synthase inhibitor, N(G)-nitro-L-arginine (20 microM). It was shown that
      changes in microvascular pressure accompanying changes in U during free perfusion
      could account for only 15 % of the changes in P(S), i.e. 85 % of the changes in
      P(S) were changes in the permeability coefficient itself. A comparison between
      the changes in P(S) with U and the previously described changes in microvascular
      permeability to K(+) with U, suggest that if the flow-dependent component of
      permeability is modelled as a population of pores of constant size, these have
      radii of 0.8 nm. Such a pathway would limit flow-dependent permeability to small
      hydrophilic molecules and have minimal effect on net fluid exchange.

PMID- 12231652
TI  - NO- and non-NO-, non-prostanoid-dependent vasodilatation in rat sciatic nerve
      during maturation and developing experimental diabetic neuropathy.
AB  - This study examined NO- and non-NO-, non-prostanoid-dependent pathways of agonist
      induced vasodilatation in streptozotocin (STZ)-induced diabetic rats and their
      age-matched controls at 1-2, 8-10 and 18-20 weeks after induction of diabetes.
      Using laser Doppler flowmetry, vasodilatory responses to acetylcholine (ACh; 0.1
      mM) and morpholino-sydnonimine (SIN-1) were determined in the presence of Ringer
      solution, during inhibition of NO synthase (NOS) and cyclo-oxygenase (COX) with
      N(omega)-nitro-L-arginine (L-NNA; 1 mM) + indomethacin (10(-5) M), and during
      inhibition of K(+) channels, NOS and COX with tetraethylammonium (TEA; 10 mM) + L
      NNA + indomethacin. Basal NOS activity and nerve conduction velocity were also
      determined. In age-matched controls, SIN-1-induced vasodilatation in the presence
      of TEA + L-NNA + indomethacin, basal NOS activity and the initial vasodilatory
      response to ACh during NOS and COX inhibition all decreased with maturation. In
      STZ-induced diabetics, SIN-1-induced vasodilatation in the presence of TEA + L
      NNA + indomethacin was impaired immediately after induction of diabetes, but not
      at 18-20 weeks. NOS activity in STZ-induced diabetics displayed a transient 2
      fold increase at 8-10 weeks, decreasing to age-matched control levels at 18-20
      weeks. At 18-20 weeks of STZ-induced diabetes, ACh-induced vasodilatation during
      NOS and COX inhibition was prolonged due to increased K(+) channel activity and
      experimental diabetic sensory neuropathy (EDN) had developed. Thus, in sciatic
      nerve microcirculation of STZ-induced diabetic rats: (1) diabetic impairment of
      vasodilatation in response to exogenous NO was transient; (2) non-NO-, non
      prostanoid-dependent vasodilatation and K(+) channel activity were augmented in
      STZ-induced diabetes; and (3) alterations in NO bioactivity were not related to
      the development of EDN.

PMID- 12231653
TI  - Sensory afferent selective role of P2 receptors in the nucleus tractus solitarii
      for mediating the cardiac component of the peripheral chemoreceptor reflex in
      rats.
AB  - We have assessed the functional role of type 2 purinergic (P2) receptors within
      the caudal aspect of the commissural nucleus tractus solitarii (NTS) in mediating
      the peripheral chemoreceptor reflex cardiorespiratory response in the arterially
      perfused in situ working heart-brainstem preparation of rats. Microinjection in
      NTS of either suramin (100 pmol) or pyrinoxalphosphate-6-azophenyl-2',4'
      disulphonic acid tetrasodium salt (PPADS; 10 pmol) depressed the reflex
      bradycardia (by approximately 50 %), but not the tachypnoea, following peripheral
      chemoreceptor stimulation. In contrast, the reflex bradycardia produced by
      stimulation of pharyngo-oesophageal receptors was unaffected. Furthermore,
      microinjections in NTS of the P2X receptor agonist alpha,beta-methyleneadenosine
      5'-triphosphate (10 pmol) evoked a bradycardia which was antagonized by suramin
      (100 pmol). This P2X agonist reversibly potentiated the peripheral chemoreceptor
      evoked bradycardia. The effect of suramin was selective to purinergic receptors
      because the bradycardia evoked by microinjection of alpha,beta-methyleneadenosine
      5'-triphosphate was blocked while the bradycardic responses to microinjections of
      NMDA or non-NMDA receptor agonists were not affected. From whole-cell recordings,
      some NTS neurones received convergent excitatory synaptic inputs from both
      peripheral chemoreceptors and receptors at the pharyngo-oesophageal junction. The
      excitatory postsynaptic response evoked by chemoreceptor stimulation was
      depressed by suramin, but convergent excitatory inputs from pharyngo-oesophageal
      receptors were unperturbed. Our findings support the hypothesis that caudal
      commissural NTS P2 purinergic receptors play a role in the neurotransmission of
      the parasympathetic (bradycardic) component of the chemoreceptor reflex. This
      effect is highly selective in that the chemoreceptor afferent-evoked tachypnoea,
      as well as other visceral receptor-mediated reflex bradycardia, remain
      unaffected.

PMID- 12231654
TI  - Neurokinin B induces oedema formation in mouse lung via tachykinin receptor
      independent mechanisms.
AB  - The tachykinin neurokinin B (NKB) has been implicated in the hypertension that
      characterises pre-eclampsia, a condition where tissue oedema is also observed.
      The ability of NKB, administered intradermally or intravenously, to induce oedema
      formation (assessed as plasma extravasation) was examined by extravascular
      accumulation of intravenously injected (125)I-albumin in wild-type and tachykinin
      NK(1) receptor knockout mice. Intradermal NKB (30-300 pmol) caused dose-dependent
      plasma extravasation in wild-type (P < 0.05) but not NK(1) knockout mice,
      indicating an essential role for the NK(1) receptor in mediating NKB-induced skin
      oedema. Intravenous administration of NKB to wild-type mice produced plasma
      extravasation in skin, uterus, liver (P < 0.05) and particularly in the lung (P <
      0.01). Surprisingly, the same doses of NKB led to plasma extravasation in the
      lung and liver of NK(1) knockout mice. By comparison, the tachykinin substance P
      induced only minimal plasma extravasation in the lungs of wild-type mice. The
      plasma extravasation produced by NKB in the lungs of NK(1) receptor knockout mice
      was unaffected by treatment with the NK(2) receptor antagonist SR48968 (3 mg kg(
      1)), by the NK(3) receptor antagonists SR142801 (3 mg kg(-1)) and SB-222200 (5 mg
      kg(-1)) or by the cyclo-oxygenase (COX) inhibitor indomethacin (20 mg kg(-1)). L
      Nitro-arginine methyl ester (15 mg kg(-1)), an inhibitor of endothelial nitric
      oxide synthase (eNOS), produced only a partial inhibition. We conclude that NKB
      is a potent stimulator of plasma extravasation through two distinct pathways: via
      activation of NK(1) receptors, and via a novel neurokinin receptor-independent
      pathway specific to NKB that operates in the mouse lung. These findings are in
      keeping with a role for NKB in mediating plasma extravasation in diseases such as
      pre-eclampsia.

PMID- 12231655
TI  - The role of adenosine in regulation of cerebral blood flow during hypoxia in the
      near-term fetal sheep.
AB  - The aim of this study was to determine in the near-term ovine fetus the role of
      adenosine in the basal regulation of cerebral blood flow and in the increases in
      cerebral blood flow in response to acute hypoxic insult. We measured cerebral
      blood flow in chronically instrumented fetal sheep (127-135 days gestation, term
      approximately 145 days) using laser Doppler flowmetry probes implanted in the
      parietal cortices. Hypoxia was administered for 30 min by lowering the ewe's
      inspired oxygen to 10-12 % during an infusion of either saline or theophylline, a
      non-specific adenosine receptor antagonist. The theophylline infusion was begun
      30 min prior to and ended 30 min after the completion of the hypoxic insult. The
      administration of theophylline had no significant effect on cerebral blood flow
      during the baseline period. During control hypoxic periods, cerebral blood flow
      increased by approximately 45 %. During theophylline experiments, however, there
      was no significant increase in cerebral blood flow during hypoxia. In the control
      experiments, cerebral blood flow returned to baseline levels during the recovery
      period, while in the theophylline experiments cerebral blood flow fell below
      baseline levels. We conclude that, in the near-term ovine fetus, adenosine plays
      a minimal role in the regulation of basal cerebral blood flow. However, these
      data are strong evidence for the involvement of adenosine in increased fetal
      cerebral blood flow during an acute hypoxic insult. Finally, adenosine may also
      play an important role in the maintenance of fetal cerebral blood flow
      immediately following hypoxic insult.

PMID- 12231656
TI  - Influence of different cuff inflation protocols on capillary filtration capacity
      in human calves -- a congestion plethysmography study.
AB  - It has been suggested that venous congestion plethysmography (VCP) substantially
      underestimates microvascular permeability by activation of a veni-arteriolar
      constrictor mechanism, even when using small (< 25 mmHg) congestion pressure
      steps. We studied human lower limbs of 18 young healthy volunteers to test
      whether the congestion pressure step size of the VCP protocol has an influence on
      the values of the capillary filtration capacity (CFC) and isovolumetric venous
      pressure (P(vi)). Two different dual stage VCP pressure step protocols, with 3
      and 10 mmHg steps, were used in randomised order and separated by a transient
      reduction in congestion pressure. Since lymph flow is known to increase after
      venous congestion, we also looked to see if changes in the estimated lymph flow
      (J(v)L) occur as a result of these VCP protocols. The measured CFC (median [25th;
      75th percentile]) was 2.6 [2.5; 3.2] x 10(-3) ml (100 ml)(-1) min(-1) mmHg(-1)
      with the 3 mmHg pressure step protocol, which was not different from the value of
      2.9 [2.7; 3.4] x 10(-3) ml (100 ml)(-1) min(-1) mmHg(-1) obtained with 10 mmHg
      pressure steps. However, when either of these step sizes was applied after a
      transient venous decongestion, significantly higher values of CFC, 4.0 [3.4; 4.1]
      x 10(-3) and 3.5 [3.1; 4.5] x 10(-3) ml (100 ml)(-1) min(-1) mmHg(-1),
      respectively, were obtained (P < 0.05). The assessment of P(vi) was also
      independent of the pressure protocol (10 mmHg: 8.0 [5.7; 13.2] mmHg and 3 mmHg:
      15.7 [12.5; 18.5] mmHg), but when P(vi) was measured after the transient
      deflation, significantly higher values were found with both 10 and 3 mmHg steps
      (24.1 [20.9; 27.3] and 30.4 [28.9; 30.9] mmHg, respectively; P < 0.01). The
      transient pressure reduction was associated with a rise in estimated J(v)L from
      0.04 [0.03; 0.05] to 0.12 [0.08; 0.18] and 0.04 [0.04; 0.05] to 0.09 [0.07; 0.10]
      ml (100 ml)(-1) min(-1), respectively (P < 0.01). The first stage data from these
      protocols shows that the value of CFC is not influenced by the size of the
      cumulative venous pressure steps, providing they are of 10 mmHg or less. The data
      also show that J(v)L can be estimated with small step VCP protocols. We
      hypothesise that the sudden reduction in cuff pressure after venous congestion is
      associated with a temporary upregulation of lymph flow. As the congestion
      pressure is raised again, there is a modulation of the enhanced lymph flow, such
      that the resulting CFC slope appears greater than that obtained in the first
      stage of the protocol.

PMID- 12231657
TI  - Regional fat metabolism in human splanchnic and adipose tissues; the effect of
      exercise.
AB  - This study was conducted to investigate the role of splanchnic and adipose tissue
      in the regulation of fatty acid (FA) metabolism at rest, during 1 h of semi
      recumbent cycle exercise at 60 % of maximal power output and 3 h of recovery. In
      six post-absorptive healthy volunteers catheters were placed in a radial artery,
      hepatic vein and a subcutaneous vein on the anterior abdominal wall. Whole body,
      and regional splanchnic and adipose tissue FA metabolism were measured by a
      constant infusion of the stable isotopes [U-(13)C]palmitate and [(2)H(5)]glycerol
      and according to Fick's principle. The whole body rate of extracellular FA
      reesterification was similar at rest and during exercise (approximately 290
      micromol min(-1)) and increased during recovery to a plateau of 390 micromol min(
      1). FA and triacylglycerol (TAG) uptake by adipose tissue was undetectable, but a
      constant but small glycerol uptake of approximately 25 nmol (100 g)(-1) min(-1)
      was observed. From the FA taken up by the splanchnic area, 13 % was oxidized, 5
      11 % converted to ketone bodies, and approximately 35 % incorporated in TAG
      released both at rest and at the third hour of recovery from exercise. Splanchnic
      FA reesterification could account for 51 % and 58 % of whole body extracellular
      FA reesterification, of which half was accounted for by TAG released from the
      splanchnic area, at rest and in recovery, respectively. In conclusion, in the
      post-absorptive state, adipose tissue contributes very little to extracellular FA
      reesterification and splanchnic reesterification can account for 50-60 %,
      implying that FA reesterification in other tissues is important. The
      extracellular FA reesterification rate does not change with exercise but is
      higher during recovery. Furthermore, the uptake of glycerol by adipose tissue
      indicates that adipose tissue can metabolize glycerol.

PMID- 12231659
TI  - The ergot alkaloids. II. The degradation of ergotinine with alkali. Lysergic
      acid. 1934.

PMID- 12231658
TI  - Human skeletal muscle fatty acid and glycerol metabolism during rest, exercise
      and recovery.
AB  - This study was conducted to investigate skeletal muscle fatty acid (FA) and
      glycerol kinetics and to determine the contribution of skeletal muscle to whole
      body FA and glycerol turnover during rest, 2 h of one-leg knee-extensor exercise
      at 65 % of maximal leg power output, and 3 h of recovery. To this aim, the leg
      femoral arterial-venous difference technique was used in combination with a
      continuous infusion of [U-(13)C]palmitate and [(2)H(5)]glycerol in five post
      absorptive healthy volunteers (22 +/- 3 years). The influence of contamination
      from non-skeletal muscle tissues, skin and subcutaneous adipose tissue, on FA and
      glycerol kinetics was studied by catheterization of the femoral vein in antegrade
      and retrograde directions. Substantially higher net leg FA and glycerol uptakes
      were observed with a retrograde compared to an antegrade catheter position, as a
      result of a much lower tracer-calculated leg FA and glycerol release. The whole
      body FA rate of appearance (R(a)) increased with exercise and decreased rapidly
      in recovery but stayed higher compared to pre-exercise. The leg net FA uptake
      decreased immediately on cessation of exercise to near pre-exercise level, but
      the tracer FA uptake and release decreased slowly and reached constant values
      after approximately 1.5 h of recovery similar to pre-exercise. Whole body FA
      reesterification (FA R(d) - FA oxidation; R(d), rate of disappearance) was
      approximately 400 micromol min(-1) at rest and during exercise, and increased
      during recovery to 495 micromol min(-1). Leg FA reesterification was 17 micromol
      min(-1) at rest and decreased to 9 micromol min(-1) during recovery, due to a
      larger fraction of leg FA uptake being directed to oxidation. A net glycerol
      exchange across the leg could not be detected under all conditions, but a
      substantial leg glycerol uptake was observed, which was substantially higher
      during exercise. Total body skeletal muscle FA and glycerol uptake/release was
      estimated to account for 18-25 % of whole body R(d) or R(a). IN CONCLUSION: (1)
      skeletal muscle FA and glycerol metabolism, using the leg arterial-venous
      difference method, can only be studied if contamination from skin and
      subcutaneous adipose tissue is prevented; (2) whole body FA reesterification is
      unchanged when going from rest to exercise, but is increased during recovery; (3)
      in post-absorptive man total body skeletal muscle contributes 17-24 % to whole
      body FA and glycerol turnover and FA reesterification at rest; (4) glycerol is
      taken up by skeletal muscle and the uptake increases many fold during exercise.

PMID- 12231660
TI  - Oxygen Stress and Superoxide Dismutases.

PMID- 12231661
TI  - Volatile Products of the Lipoxygenase Pathway Evolved from Phaseolus vulgaris
      (L.) Leaves Inoculated with Pseudomonas syringae pv phaseolicola.
AB  - Activation of the "lipoxygenase pathway" in plants gives rise to a series of
      products derived from fatty acids. Analysis by gas chromatography-mass
      spectroscopy of volatile products produced by Phaseolus vulgaris (L.) cv Red
      Mexican leaves during a hypersensitive resistance response (HR) to the plant
      pathogenic bacterium Pseudomonas syringae pv phaseolicola showed evolution of
      several lipid-derived volatiles, including cis-3-hexenol and trans-2-hexenal,
      which arise from the 13-hydroperoxide of linolenic acid. These compounds were not
      produced in detectable amounts by buffer-inoculated leaves, nor did they evolve
      to such a high degree during comparable stages of the susceptible response. The
      absence of trans-2,cis-6-nonadienal, a product expected from 9-hydroperoxide of
      linolenic acid, suggests that lipid peroxidation during the HR proceeded
      primarily enzymically via bean lipoxygenase, which produces the 13-hydroperoxide,
      and not via autoxidative processes. The effects of trans-2-hexenal, cis-3
      hexenol, and traumatic acid on P.s pv phaseolicola were investigaed. trans-2
      Hexenal appeared to be highly bactericidal at low concentrations, whereas cis-3
      hexenol was bactericidal only at much higher concentrations. Traumatic acid
      appeared to have no effect on P.s. pv. phaseolicola at the concentrations tested.
      These results demonstrate that during plant defense responses against microbial
      attack, several lipid-derived compounds are produced by the plant, some of which
      possess antimicrobial activity and conceivably are involved in plant disease
      resistance. The time of production of these substances, in amounts that would be
      expected to be antibacterial in vitro, correlated with a slowing down of the
      growth rate of bacteria in the leaves and was seen at a time before the
      accumulation of isoflavonoid phytoalexins in the host.

PMID- 12231662
TI  - Correlation between the Circadian Rhythm of Resistance to Extreme Temperatures
      and Changes in Fatty Acid Composition in Cotton Seedlings.
AB  - Fluctuations in fatty acid composition were examined in cotton (Gossypium
      hirsutum L. cv Deltapine 50) leaves during light-dark cycles of 12:12 h and under
      continuous light and were correlated to the rhythmic changes in chilling
      (5[deg]C) resistance (CR) and heat (53[deg]C) resistance (HR). The chilling
      resistant and chilling-sensitive phases developed in the dark or the light
      period, respectively, and this rhythm persisted under continuous light for three
      cycles. The heat-resistant phase developed in the light period and an additional
      peak of HR occurred in the middle of the dark period. Under continuous light,
      only one peak of HR developed, lasting from the middle of the subjective night to
      the middle of the subjective day. The amounts of palmitic and oleic acids were
      constant during the light-dark cycle and under continuous light, but those of
      linoleic and linolenic acids fluctuated, attaining a high level in the middle of
      the dark period or the subjective night, and a low level in the middle of the
      light period or the subjective day. A low temperature of 20[deg]C induced CR and
      affected changes in fatty acid composition similar to those that occurred during
      the daily CR phase. A high temperature of 40[deg]C induced HR but did not affect
      changes in fatty acid composition. The results in their entirety show that the CR
      that develops rhythmically as well as the low-temperature-induced CR coincide
      with increased levels of polyunsaturated fatty acids. No correlation is found
      between changes in fatty acid composition and the HR that develops rhythmically
      or the high-temperature-induced HR.

PMID- 12231663
TI  - Photosynthetic Fractionation of the Stable Isotopes of Oxygen and Carbon.
AB  - Isotope discrimination during photosynthetic exchange of O2 and CO2 was measured
      using enzyme, thylakoid, and whole cell preparations. Evolved oxygen from
      isolated spinach thylakoids was isotopically identical (within analytical error)
      to its source water. Similar results were obtained with Anacystis nidulans
      Richter and Phaeodactylum tricornutum Bohlin cultures purged with helium. For
      consumptive reactions, discrimination ([delta], where 1 + [delta]/1000 equals the
      isotope effect, k16/k18 or k12/k13) was determined by analysis of residual
      substrate (O2 or CO2). The [delta] for the Mehler reaction, mediated by
      ferredoxin or methylviologen, was 15.3[per mille (thousand) sign]. Oxygen isotope
      discrimination during oxygenation of ribulose-1,5-bisphosphate (RuBP) catalyzed
      by RuBP carboxylase/oxygenase (Rubisco) was 21.3[per mille (thousand) sign] and
      independent of enzyme source, unlike carbon isotope discrimination: 30.3[per
      mille (thousand) sign] for spinach enzyme and 19.6 to 23[per mille (thousand)
      sign] for Rhodospirillum rubrum and A. nidulans enzymes, depending on reaction
      conditions. The [delta] for O2 consumption catalyzed by glycolate oxidase was
      22.7[per mille (thousand) sign]. The expected overall [delta] for
      photorespiration is about 21.7[per mille (thousand) sign]. Consistent with this,
      when Asparagus sprengeri Regel mesophyll cells approached the compensation point
      within a sealed vessel, the [delta]18O of dissolved O2 came to a steady-state
      value of about 21.5[per mille (thousand) sign] relative to the source water. The
      results provide improved estimates of discrimination factors in several reactions
      prominent in the global O cycle and indicate that photorespiration plays a
      significant part in determining the isotopic composition of atmospheric oxygen.

PMID- 12231664
TI  - Rapid Induction of Ion Pulses in Tomato, Cucumber, and Maize Plants following a
      Foliar Application of L(+)-Adenosine.
AB  - Application of picomole quantities of (+)-adenosine, a plant growth-regulating
      second messenger elicited by triacontanol, to tomato (Lycopersicon esculentum
      Mill.), maize (Zea mays L.), and cucumber (Cucumis sativa L.) foliage, increased
      Ca2+, Mg2+, and K+ concentrations in the exudate from the stumps of excised
      plants by 20 to 60% within 5 s after treatment. The change in ionic concentration
      of the exudate was transitory. When L(+)-adenosine and triacontanol were applied
      to different tomato plants at the same time, the L(+)-adenosine caused an
      increase in Ca2+ flux within 3 s, whereas a significant increase from
      triacontanol was not detectable until 5 min after application. This was expected
      because triacontanol elicits the formation of L(+)-adenosine. The enantiomer of
      L(+)-adenosine, D(-)-adenosine, had no effect on the cation concentration in
      tomato and inhibited the effect of L(+)-adenosine at equimolar or lower
      concentrations. These observations suggest that L(+)-adenosine acts by eliciting
      a rapidly propagated signal that increases the concentration of several ions in
      the apoplast. We postulate that modulations in apoplastic ion concentration,
      especially increases in Ca2+ concentration, constitute a mechanism by which
      plants regulate metabolic activity and growth in response to certain stimuli.

PMID- 12231665
TI  - Purification and Light-Dependent Molecular Modulation of the Cytosolic Fructose
      1,6-Bisphosphatase in Sugarbeet Leaves.
AB  - Cytosolic fructose-1,6-bisphosphatase (FBPase) was purified 472-fold from
      sugarbeet (Beta vulgaris L.) leaves by ammonium sulfate fractionation, anion
      exchange chromatography (DEAE Sepharose), cation-exchange chromatography (S
      Sepharose), gel filtration (Sephacryl S-300), and hydrophobic interaction
      chromatography (Phenyl Sepharose). The dissociated polypeptide (molecular mass of
      37 kD) was used to generate polyclonal antibodies. Western blot analysis revealed
      a single band that was identified as the cytosolic FBPase. Enzyme activity and
      protein and transcript levels were measured under various light and dark
      conditions in growth chamber-grown plants. FBPase protein level remained
      unchanged during a diurnal cycle, but enzyme activity and transcript levels were
      highest and lowest at the end of the light and dark periods, respectively. Light
      dependent increase in the enzyme activity and transcript level was gradual,
      occurring several hours after the onset of light. At the end of an extended dark
      period (48 h), FBPase activity was negligible, protein level was unchanged, and
      transcript level had declined (but considerable amounts of transcript remained).
      Neither activity nor protein and transcript were detected in etiolated leaves.
      Nearly 24 h of continuous exposure to light was required before the FBPase
      protein and activity reached maximal levels. Unlike the chloroplastic FBPase,
      which is light activated (direct regulation), changes in the cytosolic FBPase
      activity and transcription appear to be light dependent in an indirect manner.
      The data provide first evidence on the coarse control of this enzyme via a light
      dependent modulation of transcription and posttranslational modification.

PMID- 12231666
TI  - The pH Dependence of Violaxanthin Deepoxidation in Isolated Pea Chloroplasts.
AB  - The absorbance change at 505 nm was used to monitor the kinetics of violaxanthin
      deepoxidation in isolated pea (Pisum sativum) chloroplasts under dark conditions
      at various pH values. In long-term measurements (65 min) a fast and a slow
      exponential component of the 505-nm absorbance change could be resolved. The fast
      rate constant was up to 10 times higher than the slow rate constant. The
      asymptote value of the fast kinetic component was twice that of the slow
      component. The pH dependency of the parameters of the fast kinetic component was
      analyzed from pH 5.2 to pH 7.0. It was found that the asymptote value dropped
      slightly with increasing pH. The rate constant was zero at pH values greater than
      6.3 and showed maximum values at pH values less than 5.8. Hill plot analysis
      revealed a strong positive cooperativity for the pH dependency of the fast rate
      constant (Hill coefficient nH = 5.3). The results are discussed with respect to
      published activity curves of violaxanthin deepoxidation.

PMID- 12231667
TI  - Starch Degradation and Distribution of the Starch-Degrading Enzymes in Vicia faba
      Leaves (Diurnal Oscillation of Amylolytic Activity and Starch Content in
      Chloroplasts).
AB  - Subcellular localization of the starch-degrading enzymes in Vicia faba leaves was
      achieved by an electrophoretic transfer method through a starch-containing gel
      (SCG) and enzyme activity measurements. Total amylolytic and phosphorolytic
      activities were found predominantly in the extrachloroplastic fraction, whereas
      the debranching enzymes showed homogenous distribution between stromal and
      extrachloroplastic fractions. Staining of end products in the SCG revealed two
      isoforms of [alpha]-amylase (EC 3.2.1.1) and very low [beta]-amylase activity (EC
      3.2.1.2) in the chloroplast preparation, whereas [alpha]- and [beta]-amylase
      exhibited higher activities in the crude extract. However, it is unclear whether
      the low [alpha]- and [beta]-amylase activities associated with the chloroplast
      are contamination or activities that are integrally associated with the
      chloroplast. Study of the diurnal fluctuation of the starch content and of the
      amylase activities under a 9-h/15-h photoperiod showed a 2-fold increase of the
      total amylolytic activity in the chloroplasts concurrent with the starch
      degradation in the dark. No fluctuation was detectable for the extrachloroplastic
      enzymes. The possible roles and function of the chloroplastic and
      extrachloroplastic hydrolytic enzymes are discussed.

PMID- 12231670
TI  - Photosynthesis, Rubisco Activity and Amount, and Their Regulation by
      Transcription in Senescing Soybean Leaves.
AB  - Senescence is a phase of leaf ontogeny marked by declining photosynthetic
      activity that, in soybean (Glycine max [L.] Merr.), is paralleled by a decline in
      chloroplast function. Soybean leaves have different patterns of decline in
      photosynthetic capacity and chloroplast function associated with nodal position
      and sink activity. The objective of this work was to determine whether leaves
      from nodes 3 and 6 of soybean, which show these different patterns, are similarly
      regulated with respect to ribulose-1,5-bisphosphate carboxylase/oxygenase
      (Rubisco) activity and content and also to ascertain the degree of regulation of
      Rubisco content by transcription. Leaves from nodes 3 and 6 of field-grown
      soybean plants were sampled periodically from the time of their unfolding until
      near death. In situ CO2-exchange rate (CER) increased to a maximal level in both
      leaves and then declined slowly. For node 3 leaves the decline was progressive,
      but for node 6 leaves the decline was arrested at about 75% of maximum CER for a
      period of about 20 d, coincident with the onset of rapid seed growth, before a
      short period of very rapid decline immediately preceding leaf death. Rubisco
      activities and Rubisco content were directly correlated with CER in the leaves
      exhibiting the two different patterns. Rubisco activation ratio was similar for
      the two leaves and did not change throughout development. The primary regulator
      of photosynthesis at the physiological level, thus, was the amount of Rubisco
      protein. Decreases in Rubisco holoenzyme during senescence of both leaves were
      accompanied by coordinate decreases in the levels of mRNAs for the small and
      large subunits of Rubisco, suggesting that the decrease in Rubisco enzyme amounts
      during soybean leaf senescence is due to slower transcription rates and that
      levels of these mRNAs are coordinately controlled during senescence as they are
      during chloroplast development. However, plastid DNA template availability and
      posttranscriptional controls may also influence Rubisco content during senescence
      of these leaves. We conclude that soybean leaf photosynthesis likely unfolds
      according to a single developmental program but that modifications can be
      superimposed upon this program to maximize photosynthetic rates.

PMID- 12231669
TI  - Dissipation of the Proton Electrochemical Potential in Intact Chloroplasts (II.
      The pH Gradient Monitored by Cytochrome f Reduction Kinetics).
AB  - The potency of various uncouplers for collapsing the light-induced pH gradient
      across thylakoid membranes in intact chloroplasts was investigated by time
      resolved optical spectroscopy. The thylakoid transmembrane pH gradient
      ([delta]pH) was monitored indirectly by measuring the rate of cytochrome (Cyt) f
      reduction following a light flash of sufficient duration to create a sizable
      [delta]pH. The results show that the rate of Cyt f reduction is controlled in
      part by the internal pH of the thylakoid inner aqueous space. At pH values from
      6.5 to 8.0, the Cyt f reduction rate was maximal, whereas at lower pH values from
      6.5 to 5.5 the reduction rate decreased to 25% of the maximal rate. The ability
      of three uncouplers, nigericin, carbonylcyanide m-chlorophenylhydrazone, and
      gramicidin, to accelerate the rate of Cyt f reduction was determined for intact
      chloroplasts isolated from spinach (Spinacia oleracea). The efficacy of the
      uncouplers for collapsing the [delta]pH was determined using the empirical
      relationship between the [delta]pH and the Cyt f reduction rate. For intact
      chloroplasts, nigericin was the most effective uncoupler, followed by
      carbonylcyanide m-chlorophenylhydrazone, which interacted strongly with bovine
      serum albumin. Gramicidin D, even at high gramicidin:chlorophyll ratios, did not
      completely collapse the pH gradient, probably because it partitions in the
      envelope membranes and does not enter the intact chloroplast.

PMID- 12231668
TI  - Whole-Cell K+ Currents across the Plasma Membrane of Tobacco Protoplasts from
      Cell-Suspension Cultures.
AB  - The whole-cell configuration of the patch clamp technique was used to study both
      outward and inward ion currents across the plasma membrane of tobacco (Nicotiana
      tabacum) protoplasts from cell-suspension cultures. The ion currents across the
      plasma membrane were analyzed by the application of stepwise potential changes
      from a holding potential or voltage ramps. In all protoplasts, a voltage- and
      time-dependent outward rectifying current was present. The conductance increased
      upon depolarization of the membrane potential (to >0 mV) with a sigmoidal time
      course. The reversal potential of the outward current shifted in the direction of
      the K+ equilibrium potential upon changing the external K+ concentration. The
      outward current did not show inactivation. In addition to the outward rectifying
      current, in about 30% of the protoplasts, a time- and voltage-dependent inward
      rectifying current was present as well. The inward rectifying current activated
      upon hyperpolarization of the membrane potential (<-100 mV) with an exponential
      time course. The reversal potential of the inward conductance under different
      ionic conditions was close to the K+ equilibrium potential.

PMID- 12231672
TI  - Calcium Transport in Membrane Vesicles Isolated from Maize Coleoptiles (Effect of
      Indoleacetic Acid and Fusicoccin).
AB  - Maize (Zea mays L.) coleoptile segments loaded with 45Ca released about 50% of
      the ion after 1 h when treated with indoleacetic acid (IAA). In contrast,
      fusicoccin (FC) had no effect. The same relation was found when ATP-dependent
      Ca2+ transport, measured as 45Ca uptake, was determined in a plasmalemma-rich
      membrane vesicle fraction isolated from coleoptiles treated or untreated for 1 h
      with IAA or FC. In fact, IAA-treated membranes showed an increase in ATP
      dependent 45Ca uptake by more than 30% with respect to the control and the FC
      treatment. Ca2+ uptake in IAA-treated membranes was only slightly affected (+27%)
      by supplying calmodulin (Cam) exogenously. However, Ca2+ uptake in membranes from
      the control and FC-treated coleoptiles were stimulated (+80%) by exogenous Cam.
      Calmidazolium, a Cam antagonist, inhibited Ca2+ uptake in the IAA treatment (
      48%) to a greater extent with respect to the control and FC treatment (-33 and 
      29%, respectively). A possible relationship between the effect of IAA on the ATP
      dependent Ca2+ transport activity, the involvement of Cam, and their effect on
      growth are discussed.

PMID- 12231671
TI  - Inhibition of Thylakoid ATPase by Venturicidin as an Indicator of CF1-CF0
      Interaction.
AB  - Venturicidin inhibits the F0 portion of membrane-located, H+-pumping ATPases. We
      find it meets the criteria for an energy transfer inhibitor for spinach (Spinacia
      oleracea) thylakoids: complete inhibition of photophosphorylation and of
      photophosphorylation-stimulated and basal electron flow rates, but not of
      electron flow under uncoupled conditions. The extent of H+ uptake in the light is
      stimulated by venturicidin (vtcd), as expected for a compound blocking H+ efflux
      through CF0. Vtcd had no effect on the nonproton pumping, methanol-stimulated
      ATPase of thylakoids or on soluble CF1 ATPase. Under totally uncoupled conditions
      (saturating NH4Cl + gramicidin), vtcd can still inhibit sulfite-stimulated
      thylakoid ATPase completely. The concentration of vtcd needed for inhibition of
      ATPase was proportional to the concentration of thylakoids present in the assay,
      with an apparent stoichiometry of about 10 vtcd molecules per CF1/CF0 for 50%
      inhibition. Vtcd raised the Km for ATP somewhat, but had a stronger effect on the
      Vmax with respect to ATP. Inhibition by saturating vtcd ranged from 50 to 100%,
      depending on the condition of the thylakoids. Grinding leaves in buffer
      containing 0.2 M choline chloride (known to provide superior photophosphorylation
      rates) helped bring on maximum vtcd inhibition; trypsin treatment or aging of
      thylakoids brought on vtcd-resistant ATPase. We conclude that the extent of
      inhibition by vtcd can be used as an indicator of the tightness of coupling
      between CF1 and CF0.

PMID- 12231673
TI  - Contamination of Ammonium-Based Nutrient Solutions by Nitrifying Organisms and
      the Conversion of Ammonium to Nitrate.
AB  - Conversion of ammonium to nitrate and contamination by nitrifying organisms are
      often assumed not to be significant in ammonium-based nutrient solutions. To
      assess this assumption, maize (Zea mays) and pea (Pisum sativum) were grown under
      greenhouse conditions in aeroponic, hydroponic, and sand-culture systems
      containing 2 mM ammonium chloride as the sole nitrogen source and evaluated for
      the activity of contaminating nitrifying organisms. In all three culture systems,
      root colonization by nitrifying organisms was detected within 5 d, and nitrate
      was detected in the nutrient solution within 10 d after seedling transfer. In
      sand culture, solution nitrate concentration reached 0.35 mM by the end of the 17
      d experiment. Consistent with the microbial ammonium oxidation sequence, nitrite
      was detected earlier than nitrate and remained at lower levels throughout the
      experiment. Nitrate was found in significant quantities in root and shoot tissues
      from seedlings grown in ammonium-based nutrient solutions in all of the solution
      culture systems. Maize seedlings grown in an ammonium-based hydroponic system
      contained nitrate concentrations at 40% of that found in plants grown in nitrate
      based solution. Determination of nitrate (or nitrite) levels in the nutrient
      solution was the weakest indicator of the activity of nitrifying organisms. A
      bioassay for the presence of nitrifying organisms in combination with tissue
      analysis for nitrate was a better indicator of microbial conversion of ammonium
      to nitrate in nutrient solution culture. The results have implications for the
      use of ammonium-based nutrient solutions to obtain plants suitable for research
      on induction of nitrate uptake and reduction or for research using solution
      culture to compare ammonium versus nitrate fertilization.

PMID- 12231674
TI  - Influence of Vesicular-Arbuscular Mycorrhizal Fungi on the Response of Potato to
      Phosphorus Deficiency.
AB  - Morphological and biochemical interactions between a vesicular-arbuscular
      mycorrhizal (VAM) fungus (Glomus fasciculatum [Thaxt. sensu Gerdemann] Gerdemann
      and Trappe) and potato (Solanum tuberosum L.) plants during the development of P
      deficiency were characterized. Nonmycorrhizal (NM) plants grown for 63 d with low
      abiotic P supply (0.5 mM) produced 34, 52, and 73% less root, shoot, and tuber
      dry matter, respectively, than plants grown with high P (2.5 mM). The total leaf
      area and the leaf area:plant dry weight ratio of low-P plants were substantially
      lower than those of high-P plants. Moreover, a lower shoot:root dry weight ratio
      and tuber:plant dry weight ratio in low-P plants than in high-P plants
      characterized a major effect of P deficiency stress on dry matter partitioning.
      In addition to a slower rate of growth, low-P plants accumulated nonreducing
      sugars and nitrate. Furthermore, root respiration and leaf nitrate reductase
      activity were lower in low-P plants than in high-P plants. Low abiotic P supply
      also induced physiological changes that contributed to the greater efficiency of
      P acquisition by low-P plants than by high-P plants. For example, allocation of
      dry matter and P to root growth was less restricted by P deficiency stress than
      to shoot and tuber growth. Also, the specific activities of root acid
      phosphatases and vanadate-sensitive microsomal ATPases were enhanced in P
      deficient plants. The establishment of a VAM symbiosis by low-P plants was
      essential for efficient P acquisition, and a greater root infection level for P
      stressed plants indicated increased compatibility to the VAM fungus. By 63 d
      after planting, low-P VAM plants had recovered 42% more of the available soil P
      than low-P NM plants. However, the VAM fungus only partially alleviated P
      deficiency stress and did not completely compensate for inadequate abiotic P
      supply. Although the specific activities of acid phosphatases and microsomal
      ATPases were only marginally influenced by VAM infection, VAM roots
      characteristically had a higher protein concentration and, consequently, enhanced
      microsomal ATPase and acid phosphatase activities on a fresh weight basis
      compared with NM roots. Morphological and ultrastructural details of VAM plants
      are discussed in relation to the influence of the VAM symbiosis on P nutrition of
      potato.

PMID- 12231675
TI  - Role of Oxygen in the Limitation and Inhibition of Nitrogenase Activity and
      Respiration Rate in Individual Soybean Nodules.
AB  - Although infected cell O2 concentration (Oi) is known to limit respiration and
      nitrogenase activity in legume nodules, techniques have not been available to
      measure both processes simultaneously in an individual legume nodule.
      Consequently, details of the relationship between nitrogenase activity and Oi are
      not fully appreciated. For the present study, a probe was designed that allowed
      open circuit measurements of H2 evolution (nitrogenase activity) and CO2
      evolution (respiration rate) in a single attached soybean nodule while
      simultaneously monitoring fractional oxygenation of leghemoglobin (and thereby
      Oi) with a nodule oximeter. Compared to measurements of whole nodulated roots,
      use of the probe led to inhibition of nitrogenase activity in the single nodules.
      During oximetry measurements, total nitrogenase activity (TNA; peak H2 evolution
      in Ar/O2) in the single nodules was 16% of that in whole nodulated roots and 48%
      of nodulated root activity when Oi was not being measured simultaneously. This
      inhibition did not affect the nodules' ability to regulate Oi, because exposure
      to Ar/O2 (80:20, v/v) caused nitrogenase activity and respiration rate to
      decline, and this decline was linearly correlated with a concurrent decrease in
      Oi. When the nodules were subsequently exposed to a linear increase in external
      pO2 from 20 to 100% O2 at 2.7% O2/min, fractional leghemoglobin oxygenation first
      increased gradually and then more rapidly, reaching saturation at a pO2 between
      76 and 100% O2. Plots of nitrogenase activity and respiration rate against Oi
      showed that rates increased with Oi up to a value of 57 nM, with half-maximal
      rates being attained at Oi values between 10 and 14 nM O2. The maximum
      nitrogenase activity achieved during the increase in pO2 (potential nitrogenase
      activity) was 30 to 57% of that measured in intact nodulated roots, showing that
      O2 limitation of nitrogenase activity could account for a significant proportion
      of the inhibition of TNA associated with the use of the probe. However, some
      factor(s) in addition to O2 must have limited the activity of single nodules at
      both subsaturating and saturating Oi. At Oi values greater than about 57 nM,
      nitrogenase activity and nodule respiration were inhibited, but, because this
      inhibition has been shown previously to be readily reversible when the Oi was
      lowered, it was not attributed to direct O2 inactivation of the nitrogenase
      protein. These results indicate that maximum nitrogenase activity in legume
      nodules is supported by a narrow range of Oi values. Possible biochemical
      mechanisms are discussed for both O2 limitation of nitrogenase activity at low Oi
      and inhibition of nitrogenase activity at high Oi.

PMID- 12231676
TI  - Stimulation of Callose Synthesis in Vivo Correlates with Changes in Intracellular
      Distribution of the Callose Synthase Activator [beta]-Furfuryl-[beta]-Glucoside.
AB  - [beta]-Furfuryl-[beta]-glucoside (FG) has been shown to be a specific endogenous
      activator of higher plant callose synthase (P. Ohana, D.P. Delmer, G. Volman,
      J.C. Steffens, D.E. Matthews, M. Benziman [1992] Plant Physiol 98: 708-715).
      Because glycosides such as FG are usually sequestered in vacuoles, we have
      proposed that activation of callose synthesis in vivo may involve a change in the
      compartmentation of FG and Ca2+, resulting in a synergistic activation of callose
      synthase. The use of suspension-cultured barley (Hordeum bulbosum L.) cells
      provides evidence that FG is largely sequestered in the vacuole. Furthermore,
      conditions that lead to induction of callose synthesis in vivo correspondingly
      lead to elevation of the cytoplasmic concentration of FG. These conditions
      include the lowering of cytoplasmic pH or elevation of cytoplasmic Ca2+.
      Oligogalacturonide elicitors have also been reported to cause similar changes in
      cytoplasmic pH and Ca2+ concentration (Y. Mathieu, A. Kurkdjian, H. Xia, J.
      Guern, A. Koller, M.D. Spiro, M. O'Neill, P. Albersheim, A. Darvill [1991] The
      Plant Journal 1: 333-343), and such an elicitor also causes an elevation in
      cytoplasmic FG coupled with stimulation of callose synthesis. These results
      support the concept that a relative redistribution of FG between cytoplasm and
      vacuole may be one of the components of the signal transduction pathway for
      elicitation of callose synthase in vivo.

PMID- 12231677
TI  - Abolition of an Inducible Highly Anionic Peroxidase Activity in Transgenic
      Tomato.
AB  - Locally induced expression of a highly anionic peroxidase has previously been
      correlated temporally and spatially with suberization of tissues responding to
      pathogen assault, wounding, or exogenously applied abscisic acid or fungal
      elicitors. DNA sequences corresponding to the 5[prime] regions of two tomato
      (Lycopersicon esculentum) genes encoding homologous anionic peroxidases were
      fused, inserted into a pTi-based plasmid designed to express a composite
      antisense transcript, and introduced into tomato via Agrobacterium-mediated
      transformation. RNA gel-blot analyses showed high expression of the antisense
      transcript in most transgenic plants and no detectable induction of native
      anionic peroxidase transcripts in wounded or abscisic acid or pathogen-treated
      tissues. Plants and fruits expressing the antisense transcript appeared normal in
      all respects. Electrophoretic analysis of anionic proteins from selected
      transgenic plants showed no detectable anionic peroxidase protein or activity.
      Depolymerization of polymeric material from the wound periderm of transgenic
      tomato fruits and analysis of the aliphatic products by gas-liquid
      chromatography/mass spectrometry showed that the content and composition of
      C16/C18 [omega]-hydroxy and dicarboxylic acids, characteristic of suberin, were
      not affected by the absence of the anionic peroxidase. Autofluorescence generated
      from cell wall phenolics at the wound lesion was also not affected by the absence
      of the highly anionic peroxidase.

PMID- 12231678
TI  - Constitutive and Inducible Aerobic and Anaerobic Stress Proteins in the
      Echinochloa Complex and Rice.
AB  - Anaerobic stress resulted in a change in the protein accumulation patterns in
      shoots of several Echinochloa (barnyard grass) species and Oryza sativa (L.)
      (rice) as resolved by two-dimensional gel electrophoresis. Of the six Echinochloa
      species investigated, E. phyllopogon (Stev.) Koss, E. muricata (Beauv.) Fern, E.
      oryzoides (Ard.) Fritsch Clayton, and E. crus-galli (L.) Beauv. are tolerant of
      anaerobiosis and germinate in the absence of oxygen, as does rice. In contrast,
      E. crus-pavonis (H.B.K.) Schult and E. colonum (L.) Link are intolerant and do
      not germinate without oxygen. Computer analysis of the protein patterns from the
      four tolerant species and rice indicated that the anaerobic response is of five
      classes: class 1 proteins, enhanced under anaerobiosis (9 to 13 polypeptides
      ranging from 16-68 kD); class 2 proteins, unique to anaerobiosis (1 to 5
      polypeptides ranging from 17-69 kD); class 3 proteins, remained constant under
      aerobiosis and anaerobiosis; class 4 proteins, prominent only in air and
      repressed under anoxia (3 to 7 polypeptides ranging from 19-45 kD); and class 5
      proteins, unique to aerobiosis (1 to 4 polypeptides ranging from 18-63 kD). In
      the intolerant species, E. colonum and E. crus-pavonis, no polypeptides were
      enhanced or repressed under anoxia (class 1 and class 4, respectively), whereas
      in the tolerant Echinochloa species and rice, a total of at least 9 to 13
      anaerobic stress proteins and 4 to 7 "aerobic" proteins were noted.
      Immunoblotting identified two of the major anaerobic stress proteins as fructose
      1,6-bisphosphate aldolase and pyruvate decarboxylase. Based on the differential
      response of the intolerant species to anaerobiosis, we suggest that another set
      of genes, whose products may not necessarily be among the major anaerobic stress
      polypeptides, might confer tolerance in Echinochloa under prolonged anaerobic
      stress.

PMID- 12231679
TI  - Localization of Branching Enzyme in Potato Tuber Cells with the Use of
      Immunoelectron Microscopy.
AB  - Potato branching enzyme, a key enzyme in the biosynthesis of starch, was
      localized in amyloplasts in starch-storage cells of potato (Solanum tuberosum L.)
      with the use of immunogold electron microscopy. Branching enzyme was found in the
      amyloplast stroma, concentrated at the interface of the stroma and the surface of
      the starch granule. ADP-glucose pyrophosphorylase, a key regulatory enzyme in
      starch synthesis, was localized for comparison to exclude possible artifacts. ADP
      glucose pyrophosphorylase, in contrast with branching enzyme, proved to be evenly
      distributed throughout the stroma. Branching enzyme also appears to be present in
      a membrane-bounded inclusion body in the stroma, whereas ADP-glucose
      pyrophosphorylase is not. The presence of branching enzyme predominantly at the
      surface of the starch granule indicates that branching takes place at that
      surface and not throughout the amyloplast stroma.

PMID- 12231680
TI  - Low-Temperature Effects on Photosynthesis and Correlation with Freezing Tolerance
      in Spring and Winter Cultivars of Wheat and Rye.
AB  - Winter cultivars of rye (Secale cereale L., cv Musketeer) and wheat (Triticum
      aestivum L. cvs Kharkov and Monopol), but not a spring cultivar of wheat
      (Glenlea), grown at cold-hardening temperatures showed, at high irradiances, a
      higher proportion of oxidized to reduced primary, stable quinone receptor (QA)
      than did the same cultivars grown under nonhardening conditions. In addition,
      there was a positive correlation between the effects of low-growth temperature on
      this increased proportion of oxidized QA, and a concomitant increase in the
      capacity for photosynthesis, and LT50, the temperature at which 50% of the
      seedlings are killed, in cultivars showing different freezing tolerances. This
      suggests that low-temperature modulation of the photosynthetic apparatus may be
      an important factor during the induction of freezing resistance in cereals.
      Finally, the control of photosystem II photochemistry by nonphotochemical
      quenching of excitation energy was identical for nonhardened and cold-hardened
      winter rye. However, examination of measuring temperature effects per se revealed
      that, irrespective of growth temperature, nonphotochemical quenching exerted a
      stronger control on photosystem II photochemistry at 10[deg] C rather than at
      20[deg] C.

PMID- 12231681
TI  - Patterns of Effective Permeability of Leaf Cuticles to Acids.
AB  - Plants in the field are frequently exposed to anthropogenic acid precipitation
      with pH values of 4 and below. For the acid to directly affect leaf tissues, it
      must pass through the leaf cuticle, but little is known about the permeability of
      cuticles to protons, or about the effect of different anions on this
      permeability. We investigated the movement of protons through isolated astomatous
      leaf cuticles of grapefruit (Citrus X paradisi Macfady.), rough lemon (Citrus
      limon [L.] Burm. fils cv Ponderosa), and pear (Pyrus communis L.) using
      hydrochloric, sulfuric, and nitric acids. Cuticles were enzymically isolated from
      leaves and placed in a diffusion apparatus with pH 4 acid on the morphological
      outer surface of the cuticle and degassed distilled water on the inner surface.
      Changes in pH of the solution on the inner surface were used to determine rates
      of effective permeability of the cuticles to the protons of these acids. Most
      cuticles exhibited an initial low permeability, lasting hours to days, then after
      a short transition displayed a significantly higher permeability, which persisted
      until equilibrium was approached. The change in effective permeability appears to
      be reversible. Effective permeabilities were higher for sulfuric acid than for
      the others. A model of the movement of protons through the cuticle is presented,
      proposing that dissociated acid groups in channels within the cutin are first
      protonated by the acid, accounting for the low initial effective permeability;
      then protons pass freely through the channels, resulting in a higher effective
      permeability.

PMID- 12231682
TI  - Lipids, Proteins, and Structure of Seed Oil Bodies from Diverse Species.
AB  - Oil bodies isolated from the mature seeds of rape (Brassica napus L.), mustard
      (Brassica juncea L.), cotton (Gossypium hirsutum L.), flax (Linus usitatis
      simum), maize (Zea mays L.), peanut (Arachis hypogaea L.), and sesame (Sesamum
      indicum L.) had average diameters that were different but within a narrow range
      (0.6-2.0 [mu]m), as measured from electron micrographs of serial sections. Their
      contents of triacylglycerols (TAG), phospholipids, and proteins (oleosins) were
      correlated with their sizes. The correlation fits a formula that describes a
      spherical particle surrounded by a shell of a monolayer of phospholipids embedded
      with oleosins. Oil bodies from the various species contained substantial amounts
      of the uncommon negatively charged phosphatidylserine and phosphatidylinositol,
      as well as small amounts of free fatty acids. These acidic lipids are assumed to
      interact with the basic amino acid residues of the oleosins on the surface of the
      phospholipid layer. Isoelectrofocusing revealed that the oil bodies from the
      various species had an isoelectric point of 5.7 to 6.6 and thus possessed a
      negatively charged surface at neutral pH. We conclude that seed oil bodies from
      diverse species are very similar in structure. In rapeseed during maturation, TAG
      and oleosins accumulated concomitantly. TAG-synthesizing acyltransferase
      activities appeared at an earlier stage and peaked during the active period of
      TAG accumulation. The concomitant accumulation of TAG and oleosins is similar to
      that reported earlier for maize and soybean, and the finding has an implication
      for the mode of oil body synthesis during seed maturation.

PMID- 12231684
TI  - Photoacclimation of Prochlorococcus sp. (Prochlorophyta) Strains Isolated from
      the North Atlantic and the Mediterranean Sea.
AB  - Two Atlantic (SARG and NATL1) strains and one Mediterranean (MED) strain of
      Prochlorococcus sp., a recently discovered marine, free-living prochlorophyte,
      were grown over a range of "white" irradiances (lg) and under low blue light to
      examine their photoacclimation capacity. All three strains contained divinyl (DV)
      chlorophylls (Chl) a and b, both distinguishable from "normal" Chls by their red
      shifted blue absorption maximum, a Chl c-like pigment at low concentration,
      zeaxanthin, and [alpha]-carotene. The presence of two phaeophytin b peaks in
      acidified extracts from both Atlantic strains grown at high lg suggests that
      these strains also had a normal Chl b-like pigment. In these strains, the total
      Chl b to DV-Chl a molar ratio decreased from about 1 at 7.5 [mu]mol quanta m-2 s
      1 to 0.4 to 0.5 at 133 [mu]mol quanta m-2 s-1. In contrast, the MED strain always
      had a low DV-Chl b to DV-Chl a molar ratio, ranging between 0.13 at low lg and
      0.08 at high lg. The discrepancies between the Atlantic and MED strains could
      result from differences either in the number of light-harvesting complexes (LHC)
      II per photosystem II or in the Chl b-binding capacity of the apoproteins
      constituting LHC II. Photosynthesis was saturated at approximately 5 fg C(fg Chl)
      1 h-1 or 6 fg C cell-1 h-1, and growth was saturated at approximately 0.45 d-1
      for both MED and SARG strains at 18[deg]C, but saturating irradiances differed
      between strains. Atlantic strains exhibited increased light-saturated rates and
      quantum yield for carbon fixation under blue light.

PMID- 12231683
TI  - Alteration of Gene Expression Associated with Abscisic Acid-Induced Chilling
      Tolerance in Maize Suspension-Cultured Cells.
AB  - ABA induces chilling tolerance in maize (Zea mays L., cv Black Mexican Sweet)
      suspension-cultured cells at 28[deg] C when ABA was added to the culture medium
      at least 6 h prior to chilling (4[deg] C), and this induction can be inhibited by
      blocking protein synthesis with cycloheximide treatment (Z. Xin, P.H. Li [1992]
      Plant Physiol 99: 707-711). De novo synthesis of proteins and changes in poly(A+)
      RNAs were investigated during the ABA induction of chilling tolerance at 28[deg]
      C as well as during chilling exposure. At 28[deg] C, ABA increased the net
      synthesis of 11 proteins. Five of these proteins, whose net synthesis was also
      increased by chilling (4[deg] C), were called group I ABA-induced proteins; the
      remaining six proteins, whose net synthesis was not altered by chilling, were
      called group II ABA-induced proteins. Chilling suppressed the net synthesis of
      three proteins. ABA treatment prior to chilling did not alleviate this
      suppression. ABA applied at the inception of chilling induced neither chilling
      tolerance nor accumulation of any of the group II proteins; however, once the
      group II proteins appeared, they were continually synthesized even in a chilling
      regimen. ABA induced seven in vitro translation products at 28[deg] C. Three of
      these products could also be induced by chilling; the remaining four were induced
      by ABA only at 28[deg] C. These results suggest that ABA-induced alteration of
      protein synthesis at 28[deg] C is associated with an increased chilling tolerance
      in maize suspension-cultured cells.

PMID- 12231685
TI  - Stimulation of Barley Plasmalemma H+-ATPase by Phytotoxic Peptides from the
      Fungal Pathogen Rhynchosporium secalis.
AB  - A small family of necrosis-inducing peptides has been identified as virulence
      factors of Rhynchosporium secalis, a fungal pathogen of barley (Hordeum vulgare
      L.) Two members of this family, NIP1 and NIP3, were found to stimulate the
      phosphohydrolyzing activity of the Mg2+-dependent, K+-stimulated H+-ATPase of
      plasma membrane vesicles isolated from barley leaves by partitioning in an
      aqueous two-phase system. Stimulation of enzyme activity was saturated by 10 to
      15 [mu]M fungal protein. Another member of the peptide family, NIP2, did not
      affect the enzyme, indicating that it has a different mode of action.

PMID- 12231686
TI  - Studies of the Enzymic Capacities and Transport Properties of Pea Root Plastids.
AB  - Plastids have been isolated from pea (Pisum sativum L.) roots with a high degree
      of purity and intactness. In these plastids, the activity of enzymes involved in
      carbohydrate metabolism have been analyzed and corrected for cytosolic
      contamination. The results show that fructose-1,6-bisphosphatase, NAD
      glyceraldehyde phosphate dehydrogenase, and phosphoglyceromutase are not present
      in pea root plastids. Transport measurements revealed that inorganic phosphate,
      dihydroxyacetone phosphate (DHAP), 3-phosphoglycerate, 2-phosphoglycerate,
      phosphoenolpyruvate, and glucose-6-phosphate (Glc6p) are transported across the
      envelope in a counterexchange mode. Transport of glucose-1-phosphate was
      definitely excluded. The oxidation of Glc6P by intact plastids resulted almost
      exclusively in the formation of DHAP. The parallel measurement of DHAP formation
      and NO2- consumption during Glc6P-supported nitrite reduction yielded a ratio of
      NO2-reduced/DHAP formed of 1.6, which is relatively close to the theoretical
      value of 2.0. These results show that the oxidation of Glc6P, involving the
      uptake of Glc6P and the release of DHAP, and the reduction of NO2- are very
      tightly coupled to each other.

PMID- 12231687
TI  - Conjugation of Indole-3-Acetic Acid (IAA) in Wild-Type and IAA-Overprodcing
      Transgenic Tobacco Plants, and Identification of the Main Conjugates by Frit-Fast
      Atom Bombardment Liquid Chromatography-Mass Spectrometry.
AB  - Transgenic plants overproducing indole-3-acetic acid (IAA) from expression of the
      Agrobacterium tumefaciens T-DNA IAA biosynthesis genes were used to study the
      conjugation of IAA. At the 11-node stage, free IAA, as well as ester- and amide
      conjugated IAA, was analyzed in wild-type tobacco SR1 and in transgenic plants
      denoted 35S-iaaM/iaaH (line C) and 35S-iaaM x 35S-iaaH (line X). The transgenic
      plants contained increased levels of both free and conjugated IAA, and the main
      increase in IAA conjugates occurred in amide conjugates. Two amide conjugates
      were identified by fritfast atom bombardment liquid chromatography-mass
      spectrometry as indole-3-acetylaspartic acid (IAAsp) and indole-3-acetylglutamic
      acid (IAGlu), and one ester conjugate was identified as indole-3-acetylglucose.
      IAAsp and IAGlu were also identified as endogenous substances in wild-type
      plants. In wild-type plants, the percent of total IAA in the free form was
      significantly higher in young leaves (73 [plus or minus] 7%, SD) than in old
      leaves (36 [plus or minus] 8%), whereas there was no difference between young (73
      [plus or minus] 8%) and old internodes (70 [plus or minus] 9%). In IAA
      overproducing transformants, both free and conjugated IAA levels were increased,
      but the percent free IAA was maintained constant (57 [plus or minus] 10%) for
      both leaves and internodes, independent of the total IAA level or tissue age.
      These results suggest that synthesis or transport of IAA conjugates is regulated
      in the vegetative wild-type plant, and that different organs possess a unique
      balance between free and conjugated IAA. The IAA-overproducing plant, however,
      acquires a lower proportion of free IAA in the stem and younger leaves,
      presumably determined by a higher conjugation in those tissues compared with wild
      type.

PMID- 12231688
TI  - Sucrose Synthase, Starch Accumulation, and Tomato Fruit Sink Strength.
AB  - Contrasting evidence has accumulated regarding the role of acid invertase and
      sucrose synthase in tomato fruit sink establishment and maintenance. In this work
      the relationships among the activities of sucrose synthase and acid invertase,
      Lycopersicon esculentum Mill cv UC-82B fruit growth, and starch accumulation were
      analyzed in fruit at 0 to 39 d after anthesis. Sucrose synthase, but not acid
      invertase, was found to be positively correlated with tomato fruit relative
      growth rate and with starch content in the pericarp tissue. A similar association
      between sucrose synthase activity and starch accumulation was also evident in the
      basal portion of the stem. Heat-shock treatments, which inhibited the increase in
      sucrose synthase activity at the beginning of the light period and had no effect
      on acid invertase activity, were used to examine the importance of sucrose
      synthase in relation to sucrose metabolism and starch synthesis. After the heat
      shock treatment, concomitantly with the suppressed sucrose synthase activity
      relative to the controls, there was a reduction in sucrose cleavage and starch
      accumulation. These data substantiate the conclusion that, during the early
      phases of tomato fruit development, sucrose synthase rather than acid invertase
      is the dominant enzyme in metabolizing imported sucrose, which in turn plays a
      part in regulating the import of sucrose into the fruit.

PMID- 12231689
TI  - Metabolic Adaptations of Plant Respiration to Nutritional Phosphate Deprivation.
AB  - Plants respond adaptively to orthophosphate (Pi) deprivation through the
      induction of alternative pathways of glycolysis and mitochondrial electron
      transport. These respiratory bypasses allow respiration to proceed in Pi
      deficient plant cells because they negate the necessity for adenylates and Pi,
      both pools of which are severely depressed following nutritional Pi starvation.

PMID- 12231691
TI  - Green Roots: Photosynthesis and Photoautotrophy in an Underground Plant Organ.
AB  - The potential for photosynthetic and photoautotrophic growth was studied in hairy
      root cultures of Asteraceae and Solanaceae species. Upon transfer to light,
      initially heterotrophic root cultures of Acmella oppositifolia and Datura innoxia
      greened rapidly, differentiated chloroplasts, and developed light-dependent CO2
      fixation in the cortical cells. Photosynthetic potential was expressed in root
      cultures of all the Asteraceae genera examined (Acmella, Artemisia, Rudbeckia,
      Stevia, and Tagetes). Hairy roots of A. oppositifolia and D. innoxia were further
      adapted to photoautotrophy by growing in the presence of light and added CO2 (1
      5%) and by direct or sequential transfers into media containing progressively
      lower sugar concentrations. The transition to photoautotrophy was accompanied by
      an increase in CO2 fixation and in the specific activity of 1,5-ribulose
      bisphosphate carboxylase/ oxygenase (Rubisco). During the adaptation of A.
      oppositifolia roots to photoautotrophy, the ratio of Rubisco to
      phosphoenolpyruvate carboxylase increased significantly, approaching that found
      in the leaves. The levels and patterns of alkaloids and polyacetylenes produced
      by Solanaceae and Asteraceae hairy roots, respectively, were dramatically altered
      in photomixotrophic and photoautotrophic cultures. Photoautotrophic roots of A.
      oppositifolia have been mainitained in vitro for over 2 years.

PMID- 12231692
TI  - Tobacco and Parsley 4-Coumarate:Coenzyme A Ligase Genes Are Temporally and
      Spatially Regulated in a Cell Type-Specific Manner during Tobacco Flower
      Development.
AB  - The enzyme 4-coumarate:coenzyme A ligase (4CL) plays a key role in
      phenylpropanoid metabolism by supplying the precursors (coenzyme A esters of
      cinnamic acid derivatives) used for the biosynthesis of diverse natural products,
      many of which play functional roles in floral organs. In this study, we used in
      situ hybridization and histochemical localization of [beta]-glucuronidase (GUS)
      activity to define in detail the temporal and spatial patterns of 4CL-1
      expression during tobacco flower development. Sectioned flowers from tobacco
      plants transgenic for a complete copy of the parsley (Petroselinum crispum) 4CL-1
      gene were hybridized to probes that distinguished between 4CL-1 transcripts and
      endogenous tobacco 4CL transcripts. Both probes hybridized with similar cell type
      specific patterns to carpels, anthers, petals, and sepals, and the sites of
      hybridization varied during flower development. The sites of hybridization
      generally coincided temporally and spatially with sites of 4CL-GUS expression,
      suggesting that most of the expression patterns are regulated by 4CL-1 promoter
      sequences, but lack of correlation between sites of 4CL mRNA accumulation and GUS
      activity in portions of the petal suggest that downstream sequences may mediate
      some aspects of developmentally regulated 4CL-1 expression. These results
      indicate that the introduced 4CL-1 gene correctly responds to endogenous tobacco
      developmental signals and demonstrate complex temporal and spatial patterns of
      expression during floral organ differentiation.

PMID- 12231693
TI  - Differential Reactivity of [beta]-Carotene Isomers from Dunaliella bardawil
      Toward Oxygen Radicals.
AB  - Dunaliella bardawil accumulates massive amounts of [beta]-carotene in two
      isoforms, a 9-cis and an all-trans stereoisomer, when grown under high
      irradiance, as a means to protect the cells against photoinhibition (A. Ben
      Amotz, A. Shaish, M. Avron [1989] Plant Physiol 91: 1040-1043). The purpose of
      this work has been to find out if the mechanism of protection involves scavenging
      of reactive oxygen species. For this purpose high- and low-[beta]-carotene
      containing cells were compared with respect to their sensitivity to several
      external oxidants [H2O2, methyl viologen, rose bengal, and 2,2[prime]-azobis(2
      amidinopropane)HCl]. All oxidants induce a light-stimulated degradation of [beta]
      carotene and of chlorophyll. The degradation of [beta]-carotene precedes that of
      chlorophyll, indicating that it is more reactive toward oxidants. The 9-cis
      [beta]-carotene is degraded faster than the all-trans stereoisomer when exposed
      to oxidants, both in intact cells and in isolated [beta]-carotene globules,
      indicating that it is a more effective scavenger of reactive oxygen species.
      Comparison of the sensitivity to different oxidants, between high- and low-[beta]
      carotene-containing cells, reveals similar rates of chlorophyll and [beta]
      carotene degradation in the two populations. Survival tests toward H2O2 and rose
      bengal show that high-[beta]-carotene cells have a similar sensitivity toward
      H2O2 but are more resistant toward rose bengal, a photoactivated generator of
      singlet oxygen, possibly due to masking of the latter by [beta]-carotene. These
      results suggest that the protection mechanism of massively accumulated [beta]
      carotene in Dunaliella against photoinhibition is not due to scavenging of
      reactive oxygen species.

PMID- 12231694
TI  - A Kinetic and Microautoradiographic Analysis of [14C]Sucrose Import by Developing
      Wheat Grains.
AB  - Assimilates enter developing wheat grains via a strand of phloem extending along
      the crease region of the grain. After phloem unloading, they move several hundred
      micrometers before being released into the endosperm cavity, from which they are
      absorbed by the developing endosperm. Extraphloem assimilate pools in the
      maternal tissue of the crease, therefore, play a central role in post-phloem
      transport. We investigated the location and turnover of 14C-assimilates in the
      crease tissues and endosperm cavity sap by pulse labeling the flag leaf with
      14CO2. Sucrose accounted for >90% of 14C at all times. Kinetic analysis of the
      crease sucrose pool and its depletion in excised grains showed that virtually the
      entire sucrose content of the crease tissues was involved in post-phloem
      transport and behaved basically as a single well-mixed compartment.
      Microautoradiographs also showed rapid movement of 14C throughout most of the
      crease tissues. Quantification of 14C concentration in the tissues showed a
      relatively shallow gradient of 14C and, presumably, of sucrose through the
      nucellus and chalaza. The steepest gradient in 14C content occurred in the
      vascular parenchyma between the chalaza and conducting cells (xylem and phloem).

PMID- 12231695
TI  - Calcium Antagonists Inhibit Sustained Gibberellic Acid-Induced Growth of Avena
      (Oat) Stem Segments.
AB  - The elongation response of Avena sativa (oat) stem segments to gibberellic acid
      (GA3) is of large magnitude, with high hormonal sensitivity and specificity, but
      without cell division activity. This system is therefore an excellent model for
      mechanistic studies on higher plant cell elongation and the action of
      gibberellin. At millimolar concentrations, the calcium antagonists verapamil, D
      600, nicardipine, diltiazem, bepridil, 8-(N,N,-diethylamino)-octyl-3,4,5
      trimethoxybenzoate HCl, and lanthanum substantially inhibited the growth of GA3
      treated segments but had no effect on the elongation of nonhormone-treated
      segments. Although verapamil reduced the maximum growth rate and caused premature
      cessation of growth, even preincubation of the segments with the drug prior to
      treatment with GA3 failed to inhibit the earliest measured stimulation of growth
      by the hormone. Inhibition by verapamil was not reversed by increased
      concentrations of GA3 or calcium. Neither the calcium ionophore A23187 nor
      agonist BAY K 8644 had any effect on growth. Light microscopic examination of
      epidermal peels from antagonist-treated internodal tissue revealed no obvious
      differences from the control except that the cells were not as elongated.
      Although these results may support a role for calcium ion movement in maintaining
      the GA3-induced growth of Avena stem segments, they do not support the
      involvement of calcium ion movement in the hormone-mediated initiation of growth.

PMID- 12231696
TI  - Hypoxic and Anoxic Induction of Alcohol Dehydrogenase in Roots and Shoots of
      Seedlings of Zea mays (Adh Transcripts and Enzyme Activity).
AB  - Alcohol dehydrogenase (ADH) is one of a number of enzymes of glycolysis and
      fermentation known to be synthesized preferentially under low O2 conditions. We
      examined levels of Adh1 transcripts and of ADH activity in 5-mm root tips, root
      axes (the remainder of the seminal root), and shoots of maize (Zea mays L. cv TX
      5855) seedlings. Seedlings with roots averaging about 60-mm long were transferred
      from fully aerobic conditions (solutions sparged with 40% [v/v] O2) to anaerobic
      (O2-free) conditions, or to an intermediate O2 concentration. There was no prior
      acclimation to low O2. In root tips, anoxia induced Adh1 transcripts and enzyme
      activity at 6 h, but this was followed by a rapid decline so that at 12 to 18 h
      neither were detectable and the root tips were dead. In contrast, higher levels
      of Adh1 transcripts and enzyme activity were maintained for at least 48 h in root
      axes and shoots. When induction at 6 h was measured over a wide range of O2
      concentrations, a peak in ADH activity occurred in all tissues at 4% (v/v) O2.
      Maximum levels of transcripts, however, were in the range of 0 to 4% O2,
      depending on the tissue. The time course of hypoxic induction (at 4% O2) in root
      tips showed a peak in transcript levels at 6 h, whereas ADH activity continued to
      rise throughout the 24-h experiment. These results show that in root tips, ADH
      induction by anoxia was small and transient relative to induction by hypoxia.

PMID- 12231697
TI  - Expression of an Endopeptidase (EP-C1) in Phaseolus vulgaris Plants.
AB  - Endopeptidase activity increases continually in pods of maturing fruits of French
      bean (Phaseolus vulgaris L. cv Goldstar) plants and is thought to participate in
      the protein mobilization in pods during the development of seeds (M. Endo, T.
      Minamikawa, D. Yamauchi, W. Mitsuhashi [1987] J Exp Bot 38: 1988-1995). In the
      present studies, one of the major endopeptidase forms, designated EP-C1, was
      purified as a 34-kD polypeptide from pods of maturing French bean fruits. EP-C1
      was found to be immunologically distinguished from other forms in extracts from
      pods, but homologous to SH-EP, the major cysteine endopeptidase expressed in
      cotyledons of germinating Vigna mungo seeds (W. Mitsuhashi, T. Minamikawa [1989]
      Plant Physiol 89: 274-279). The level of endopeptidase that reacted with the
      antiserum to EP-C1 increased in pods as the fruit maturation proceeded. EP-C1 was
      also immunologically detected in stems of French bean plants bearing fruits of
      later maturation stages. Protein immunoblotting showed that a 34-kD polypeptide
      corresponding to EP-C1 in molecular mass occurred in extracts from 7- to 9-d
      cotyledons of germinating French bean seeds. In addition, two other polypeptides
      with slightly higher molecular masses were observed in extracts from 3- to 5-d
      cotyledons. We suggest that these two polypeptides are intermediates involved in
      posttranslational processing of EP-C1. RNA blot hybridization with EP-C1 cDNA as
      a probe showed that EP-C1 mRNA occurred in pods of fruits at later maturing
      stages and also in cotyledons of 3- to 7-d germinating seeds.

PMID- 12231698
TI  - Leaf Isoprene Emission Rate Is Dependent on Leaf Development and the Level of
      Isoprene Synthase.
AB  - Isoprene (2-methyl-1,3-butadiene) is a major volatile hydrocarbon produced by
      many plant species. Here we report that in velvet bean (Mucuna sp.), isoprene
      emission is strongly dependent on leaf developmental state and that changes in
      extractable isoprene synthase activity parallel isoprene emission rates during
      leaf development. Both leaf emission and enzyme activity exhibit over 100-fold
      increases from leaf emergence to leaf age 14 d and exhibit similar patterns to 23
      d. This suggests that the enzyme, isoprene synthase, is responsible for the in
      vivo production of isoprene and that the level of the enzyme regulates the
      pattern of isoprene emission in response to leaf development.

PMID- 12231699
TI  - Fructan Synthesis in Excised Barley Leaves (Identification of Two Sucrose-Sucrose
      Fructosyltransferases Induced by Light and Their Separation from Constitutive
      Invertases).
AB  - Excised leaves of barley (Hordeum vulgare L.) exposed to continuous light
      accumulate large amounts of soluble carbohydrates. Carbohydrates were analyzed in
      deionized extracts by high-pressure liquid chromatography on an anion exchange
      column coupled with pulsed amperometric detection. During the first few hours of
      illumination, the main sugar to accumulate was sucrose. The levels of glucose and
      fructans (oligofructosylsucroses) increased later. The trisaccharide 1-kestose (1
      kestotriose) predominated initially among the fructans. Later, 6-kestose (6
      kestotriose) and tetra- and pentasaccharides accumulated also. Total extracts
      from barley leaves were chromatographed on a MonoQ column, and each fraction was
      assayed for enzymes of interest by incubation with 200 mM sucrose for 3 h,
      followed by carbohydrate analysis. Freshly excised leaves yielded two peaks of
      invertase, characterized by formation of fructose and glucose, but had almost no
      trisaccharide-forming activities. In leaves exposed to continuous light, two new
      enzyme activities appeared that generated fructan-related trisaccharides and
      glucose from sucrose. One of them was a sucrose-sucrose fructosyl-1-transferase
      (1-SST), producing 1-kestose exclusively: the peak fractions of this activity
      contained almost no invertase. The other was a sucrose-sucrose fructosyl-6
      transferase (6-SST), producing 6-kestose. It comigrated with one of the
      constitutive invertases on MonoQ but was separated from it by subsequent
      chromatography on alkyl Superose. Nevertheless, the preparation retained
      invertase activity, suggesting that this enzyme may act both as fructosidase and
      fructosyltransferase. When incubated with 1-kestose in addition to sucrose, this
      enzyme formed less 6-kestose but instead produced large amounts of the
      tetrasaccharide bifurcose (1&6-kestotetraose), the main fructan tetrasaccharide
      accumulating in vivo. These results suggest that two inducible enzymes, 1-SST and
      6-SST, act in concert to initiate fructan accumulation in barley leaves.

PMID- 12231700
TI  - Competitive Inhibition of Abscisic Acid-Regulated Gene Expression by
      Stereoisomeric Acetylenic Analogs of Abscisic Acid.
AB  - The properties of two enantiomeric synthetic acetylenic abscisic acid (ABA)
      analogs (PBI-51 and PBI-63) in relation to ABA-sensitive gene expression are
      reported. Using microspore-derived embryos of Brassica napus as the biological
      material and their responsiveness to ABA in the expression of genes encoding
      storage proteins as a quantitative bioassay, we measured the biological activity
      of PBI-51 and PBI-63. Assays to evaluate agonistic activity of either compound
      applied individually showed a dose-dependent increase in napin gene expression on
      application of PBI-63. Maximal activity of about 40 [mu]M indicated that PBI-63
      was an agonist, although somewhat weaker than ABA. PBI-63 has a similar
      stereochemistry to natural ABA at the junction of the ring and side chain. In
      contrast, PBI-51 showed no agonistic effects until applied at 40 to 50 [mu]M.
      Even then, the response was fairly weak. PBI-51 has the opposite stereochemistry
      to natural ABA at the junction of the ring and side chain. When applied
      concurrently with ABA, PBI-63 and PBI-51 had distinctly different properties. PBI
      63 (40 [mu]M) and ABA (5 [mu]M) combined gave results similar to the application
      of either compound separately with high levels of induction of napin expression.
      PBI-51 displayed a reversible antagonistic effect with ABA, shifting the typical
      ABA dose-response curve by a factor of 4 to 5. This antagonism was noted for the
      expression of two ABA-sensitive genes, napin and oleosin. To test whether this
      antagonism was at the level of ABA recognition or uptake, ABA uptake was
      monitored in the presence of PBI-51 or PBI-63. Neither compound decreased ABA
      uptake. Treatments with either PBI-51 or PBI-63 showed an effect on endogenous
      ABA pools by permitting increases of 5- to 7-fold. It is hypothesized that this
      increase occurs because of competition for ABA catabolic enzymes by both
      compounds. The fact that ABA pools did not decrease in the presence of PBI-51
      suggests that PBI-51 must exert its antagonistic properties through direct
      competition with ABA at a hormone-recognition site.

PMID- 12231701
TI  - Methotrexate Resistance in Datura innoxia (Uptake and Metabolism of Methotrexate
      in Wild-Type and Resistant Cell Lines).
AB  - A wild-type Datura innoxia cell line (Px4) was used to select methotrexate
      resistant cells through a stepwise procedure. Two independently selected cell
      lines, MTX161 and MTX132, were stable and shown to be 5 to 15 times more
      resistant to methotrexate than wild type. These methotrexate-resistant cells were
      similar to the wild-type cells in levels and kinetic properties of dihydrofolate
      reductase, the sensitivity of dihydrofolate reductase to methotrexate, the
      binding of [3H]methotrexate to soluble proteins, and the formation of
      methotrexate polyglutamate derivatives. High performance liquid chromatographic
      analyses indicated that methotrexate polyglutamylation is only slight and may not
      be significant in the toxicity of methotrexate to Datura cells. The uptake of
      methotrexate was also investigated in the wild-type and resistant cells. The Px4
      cells exhibited a linear uptake that lasted for 1 to 7 h. The uptake was
      saturable, pH and energy dependent, and had a Km of 65.6 nM and a Vmax of 12.5
      nmol h-1g-1 fresh weight. Neither MTX161 nor MTX132 exhibited the sustained
      uptake of methotrexate shown by the Px4 cells. As a result, there were greatly
      reduced concentrations of intracellular methotrexate in resistant cells.
      Resistant cell lines had 2- to 3-fold higher Km values for methotrexate uptake
      compared with Px4 cells. It is proposed that these cells became resistant as a
      result of a stable change in the membrane transport system for methotrexate.

PMID- 12231702
TI  - Characterization of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Activity
      during Maize Seed Development, Germination, and Seedling Emergence.
AB  - Many isoprenoid compounds are necessary for growth and development of the seed
      and seedling. The first committed step in the biosynthesis of isoprenoid
      compounds is the conversion of 3-hydroxy-3-methylglutaryl coenzyme A to
      mevalonate. This study shows that the specific activity of the rate-limiting
      enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is developmentally
      regulated during Zea mays seed development and seedling emergence. The highest
      activities were observed in seed development during stages of rapid mitotic
      divisions: 10 to 12 d after pollination in the endosperm (216.1 units) and embryo
      (140.2 units). During stages of maturation, the endosperm HMGR activity decreases
      to one-fifth the maximal activity, and the embryo activity remains high at one
      half the maximal activity. Both the endosperm and embryo HMGR activities decrease
      to a basal level (2.0 units) in the desiccated seed. At approximately 48 h after
      imbibition, the embryo HMGR activity significantly increases to 5.1 units. In
      seeds germinated under white light, root HMGR activity is 2- to 4-fold higher
      than shoot activity. In seeds germinated in the dark, both root and shoot HMGR
      activities are 1- to 5-fold higher relative to activities in light-grown seeds.

PMID- 12231703
TI  - Response of Photochemical Processes of Photosynthesis to Dinitrogen Fixation in
      Soybean.
AB  - Symbiotic N2 fixation activity brings about changes in the photochemical
      processes of photosynthesis in soybean (Glycine max L. Merr.). For a potential
      photochemical efficiency ([phi]Po) similar to that obtained with an exclusively
      mineral nutrition, soybean, at full bloom stage (R2) with a moderate N2 fixation
      activity, had a better electron transfer quantum yield ([phi]PSII) and a higher
      photochemical quenching. At the beginning seed stage (R5), corresponding to more
      intense N2 fixation, the same phenomena were enhanced; in addition, an effect on
      the photochemical (k2b) and nonphotochemical (Kn-k22) transfer rates and an
      earlier activation of the electron transfer chain were characterized using a new
      parameter, the relative induction time of PSII fluorescence (Ap/Fm). The response
      of the photochemical parameters was related to the N2 fixation level (performance
      of the host plant-microsymbiont association): the energetic cost of symbiotic N2
      fixation appeared to be met by a better photochemical efficiency of
      photosynthesis coupled with a decrease in thermal dissipation (kn - k22), by
      faster thylakoid energization, and by faster reopening of photosystem II centers
      at the time of fluorescence induction, as shown by decreased Ap/Fm.

PMID- 12231704
TI  - Characterization of Maize Acetyl-Coenzyme A Carboxylase.
AB  - Maize (Zea mays L.) leaf acetyl-CoA carboxylase (ACCase) was purified about 500
      fold by ammonium sulfate fractionation and gel filtration and blue Sepharose
      affinity and anion-exchange chromatography. Most ACCase activity (85%) recovered
      from the anion-exchange column was found in a highly purified fraction (specific
      activity 5.5 [mu]mol acid-stable product min-1 mg-1) that consisted primarily of
      a single 227-kD biotinylated polypeptide. The fraction represented 29% of the
      original activity and was designated ACCase I. A second partially purified ACCase
      activity (ACCase II) eluted earlier during anion-exchange chromatography,
      contained a single biotinylated polypeptide of 219 kD, was poorly recognized by
      antiserum raised against the ACCase I polypeptide, and was less inhibited by the
      herbicides haloxyfop or sethoxydim than was ACCase I. ACCase I and II both
      utilized propionyl-CoA as substrate about 50% as effectively as acetyl-CoA, and
      neither utilized methylcrotonyl-CoA. Immunoprecipitation with antiserum and
      protein blotting of crude extracts of leaf, embryo, and endosperm tissue and
      suspension cells indicated that most ACCase activity in these tissues was
      immunologically similar and consisted of ACCase I. Only leaves contained
      significant amounts of the ACCase II polypeptide; however, no ACCase II
      polypeptide was found in isolated mesophyll chloroplasts. The ACCase I and II
      polypeptides appear to be subunits of distinct ACCase isoforms.

PMID- 12231705
TI  - Temperature Dependence of the Linkage of Quantum Yield of Photosystem II to CO2
      Fixation in C4 and C3 Plants.
AB  - The temperature dependence of quantum yields of electron transport from
      photosystem II (PSII) ([phi]II, determined from chlorophyll a fluorescence) and
      CO2 assimilation ([phi]CO2, apparent quantum yield for CO2 assimilation) were
      determined simultaneously in vivo. With C4 species representing NADP-malic
      enzyme, NAD-malic enzyme, and phosphoenolpyruvate carboxykinase subgroups, the
      ratio of [phi]II/[phi]CO2 was constant over the temperature range from 15 to
      40[deg]C at high light intensity (1100 [mu]mol quanta m-2 s-1). A similar
      response was obtained at low light intensity (300 [mu]mol quanta m-2 s-1), except
      the ratio of [phi]II/[phi]CO2 increased at high temperature. When the true
      quantum yield for CO2 fixation ([phi]CO2*) was calculated by correcting for
      respiration in the light (estimated from temperature dependence of dark
      respiration), the ratio of [phi]II/[phi]C02* remained constant with varying
      temperature and under both light intensities in all C4 species examined. Because
      the [phi]II/[phi]CO2* ratio was the same in C4 monocots representing the three
      subgroups, the ratio was not affected by differences in the bio-chemical
      mechanism of concentrating CO2 in the bundle sheath cells. The results suggest
      that PSII activity is closely linked to the true rate of CO2 fixation in C4
      plants. The close relationship between [phi]II and [phi]CO2* in C4 species under
      varying temperature and light intensity conditions is apparently due to a common
      low level of photorespiration and a primary requirement for reductive power in
      the C3 pathway. In contrast, in a C3 plant the [phi] II/[phi]CO2* ratio is higher
      under normal atmospheric conditions than under nonphotorespiratory conditions and
      it increases with rising temperature. This decrease in efficiency in utilizing
      energy derived from PSII for CO2 fixation is due to an increase in
      photorespiration. In both the C3 and C4 species, photochemistry is limited under
      low temperature, and thus excess energy must be dissipated by nonphotochemical
      means.

PMID- 12231706
TI  - Characterization of a Lectin from Lactarius deterrimus (Research on the Possible
      Involvement of the Fungal Lectin in Recognition between Mushroom and Spruce
      during the Early Stages of Mycorrhizae Formation).
AB  - A lectin (LDetL) was isolated from carpophores of the mushroom Lactarius
      deterrimus, a specific symbiont of the spruce, by a combination of affinity,
      hydroxylapatite, and gel-filtration chromatography. Its molecular mass, as
      determined by gel filtration, is about 37,000 D, and its structure is dimeric,
      with two identical subunits assembled by noncovalent bonds. It appeared
      homogeneous on high-performance liquid chromatography gel filtration, but
      isoelectric focusing revealed microheterogeneity, with a main band in the pH zone
      near 6.5. Amino acid analysis showed that LDetL contains a large proportion of
      glycine and especially methionine. Hapten inhibition assay indicated that LDetL
      is most specific for [beta]-D-galactosyl(1->3)-D-N-acetyl galactosamine residues.
      The lectin was formed in the in vitro-cultivated mycelium, and anti-lectin
      antibodies revealed by indirect immunofluorescence the presence of lectin in the
      cell wall. Receptor sites for LDetL were found on the roots, especially on the
      root hairs, of axenically grown spruce seedlings. The lectin LDL previously
      isolated by us from the taxonomically related mushroom Lactarius deliciosus, a
      symbiont of the pine, does not bind to the spruce radicle. This suggests a role
      of the fungal lectin in recognition and specificity during the early stages of
      mycorrhizae formation.

PMID- 12231707
TI  - Assembly of in Vitro-Synthesized Large Subunits into Ribulose Bisphosphate
      Carboxylase/Oxygenase Is Sensitive to CI-, Requires ATP, and Does Not Proceed
      When Large Subunits Are Synthesized at Temperatures [greater than or equal
      to]32[deg]C.
AB  - In higher plants, ribulose bisphosphate carboxylase/oxygenase (Rubisco) consists
      of eight large "L" subunits, synthesized in chloroplasts, and eight small "S"
      subunits, synthesized as precursors in the cytosol. Assembly of these into
      holoenzyme occurs in the chloroplast stroma after import and processing of the S
      subunits. A chloroplast chaperonin interacts with the L subunits, which
      dissociate from the chaperonin before they assemble into holoenzyme. Our
      laboratory has reported L subunit assembly into Rubisco in chloroplast extracts
      after protein synthesis in leaves, intact chloroplasts, and most recently in
      membrane-free chloroplast extracts. We report here that the incorporation of in
      vitro-synthesized L subunits into holoenzyme depends on the conditions of L
      subunit synthesis. Rubisco assembly did not occur after L subunit synthesis at
      160 mM KCI. When L subunit synthesis occurred at approximately 70 mM KCI,
      assembly depended on the temperature at which L subunit synthesis took place.
      These phenomena were the result of postsynthetic events taking place during
      incubation for protein synthesis. We separated these events from protein
      synthesis by lowering the temperature during protein synthesis. Lower
      temperatures supported the synthesis of full-length Rubisco L subunits. The
      assembly of these completed L subunits into Rubisco required intervening
      incubation with ATP, before addition of S subunits. ATP treatment mobilized L
      subunits from a complex with the chloroplast chaperonin 60 oligomer. Addition of
      130 mM KCI at the beginning of the intervening incubation with ATP blocked the
      incorporation of L subunits into Rubisco. The inhibitory effect of high KCI was
      due to CI- and came after association of newly synthesized L subunits with
      chaperonin 60, but before S subunit addition. It is interesting that L subunits
      synthesized at [greater than or equal to]32[deg]C failed to assemble into Rubisco
      under any conditions. These results agree with previous results obtained in this
      laboratory using newly synthesized L subunits made in intact chloroplasts. They
      also show that assembly of in vitro-synthesized L subunits into Rubisco requires
      ATP, that CI- inhibits Rubisco assembly, and that synthesis temperature affects
      subsequent assembly competence of L subunits.

PMID- 12231708
TI  - Effects of Elevated Sucrose-Phosphate Synthase Activity on Photosynthesis,
      Assimilate Partitioning, and Growth in Tomato (Lycopersicon esculentum var
      UC82B).
AB  - The expression of a sucrose-phosphate synthase (SPS) gene from maize (Zea mays, a
      monocotyledon) in tomato (Lycopersicon esculentum, a dicotyledon) resulted in
      marked increases in extractable SPS activity in the light and the dark. Diurnal
      modulation of the native tomato SPS activity was found. However, when the maize
      enzyme was present the tomato leaf cells were unable to regulate its activation
      state. No detrimental effects were observed and total dry matter production was
      unchanged. However, carbon allocation within the plants was modified such that in
      shoots it increased, whereas in roots it decreased. There was, therefore, a
      change in the shoot:root dry weight ratio favoring the shoot. This was positively
      correlated with increased SPS activity in leaves. SPS was a major determinant of
      the amount of starch in leaves as well as sucrose. There was a strong positive
      correlation between the ratio of sucrose to starch and SPS activity in leaves.
      Therefore, SPS activity is a major determinant of the partitioning of
      photosynthetically fixed carbon in the leaf and in the whole plant. The
      photosynthetic rate in air was not significantly increased as a result of
      elevated leaf SPS activity. However, the light- and CO2-saturated rate of
      photosynthesis was increased by about 20% in leaves expressing high SPS. In
      addition, the temporary enhancement of the photosynthetic rate following brief
      exposures to low light was increased in the high SPS plants relative to controls.
      We conclude that the level of SPS in the leaves plays a pivotal role in carbon
      partitioning. Furthermore, high SPS levels have the potential to boost
      photosynthetic rates under favorable conditions.

PMID- 12231709
TI  - Evidence for a Large and Sustained Glycolytic Flux to Lactate in Anoxic Roots of
      Some Members of the Halophytic Genus Limonium.
AB  - Soil salinity and anaerobiosis often occur together. This led us to investigate
      the fermentative metabolism in roots of species from the halophytic genus
      Limonium (Plumbaginaceae). Root segments from hypoxically induced plants were
      incubated for 8 h under strict anoxia in the presence of [U-14C]glucose. In three
      species (Limonium latifolium, L. nashii, and L. humile), the pattern of 14C
      labeled end products was typical of higher plants, with a 14C flux to ethanol
      higher than that to lactate. However, in four species (L. ramosissimum, L.
      gougetianum, L perezii, and L. sinuatum), the rate of lactate fermentation was
      exceptionally high, and in the latter two species the 14C flux to lactate
      exceeded that to ethanol. These two species secreted most of the lactate produced
      into the medium. Calculations indicated that the cytoplasm would have been
      lethally acidified had this secretion not occurred. The effects of factors that
      might control lactate fermentation or secretion (O2 partial pressure, pH, salt
      concentration) were studied in two contrasting species: L. sinuatum and L.
      latifolium. In both species, the lactate:ethanol ratio was higher under hypoxia
      (0.1-3 kPa O2 partial pressure) than under strict anoxia. In L. sinuatum, this
      ratio was slightly increased by increasing the pH of the medium from 5.5 to 7.5,
      but salinity treatment had no effect. The potential contribution of lactate
      fermentation to the overall carbon and energy metabolism of halophytes is
      discussed.

PMID- 12231710
TI  - Localization of [gamma]-Glutamylcysteine Synthetase and Glutathione Synthetase
      Activity in Maize Seedlings.
AB  - Fresh weight, protein, cysteine, [gamma]-glutamylcysteine, glutathione, and the
      extractable activity of the enzymes of glutathione biosynthesis, [gamma]
      glutamylcysteine synthetase (EC 6.3.2.2) and glutathione synthetase (EC 6.3.2.3),
      were measured in roots, scutella, endosperms, and shoots of 3-, 7-, and 11-d-old
      maize (Zea mays L. cv LG 9) seedlings. In 3-d-old seedlings, the scutella
      represented 14% of the seedling fresh weight, containing 43% of total protein and
      63 and 55% of the activity of [gamma]-glutamylcysteine synthetase and glutathione
      synthetase, respectively; in 11-d-old seedlings, the corresponding values were
      4.5% for fresh weight, 8.0% for protein content, and 14 and 20% for the enzyme
      activities. The highest concentrations of thiols were found for cysteine (0.27
      mM) in the roots, for glutathione (4.4 mM) in the shoots, and for [gamma]
      glutamylcysteine (13 [mu]M) in the scutella of 3-d-old seedlings. The enzyme
      activities of roots were localized in subcellular fractions after sucrose density
      gradient centrifugation. Nearly half of the [gamma]-glutamylcysteine synthetase
      activity was detected in the root proplastids of 4-d-old seedlings, whereas <10%
      of the glutathione synthetase activity was localized in this organelle. Our
      results demonstrate the importance of scutella in glutathione synthesis in the
      early stage of seedling development. Unlike chloroplasts, root plastids show only
      a small proportion of glutathione synthetase activity.

PMID- 12231711
TI  - Light-Stimulated Apical Hook Opening in Wild-Type Arabidopsis thaliana Seedlings.
AB  - Apical hook opening and cotyledon unfolding are characteristic responses that
      occur during deetiolation of dicotyledonous seedlings. Light-stimulated apical
      hook opening and cotyledon unfolding in etiolated Arabidopsis thaliana seedlings
      appears to involve the activities of multiple photosensory systems. Red, far-red,
      and blue light are all effective in stimulating these responses in Arabidopsis.
      Stimulation of hook opening by red light and low fluence blue light is inductive,
      far-red reversible, and exhibits reciprocity, as is characteristic of many low
      fluence-dependent phytochrome-mediated responses. Far-red and high-fluence blue
      light appear to stimulate hook opening and cotyledon unfolding through high
      irradiance-response systems during long-term light treatments. Although a
      phytochrome high-irradiance-response system presumably mediates the responses in
      far-red light, the responses to high-fluence blue light may be mediated by a blue
      light-specific photosensory system.

PMID- 12231712
TI  - Characterization of Glucose-6-Phosphate Incorporation into Starch by Isolated
      Intact Cauliflower-Bud Plastids.
AB  - Intact plastids from cauliflower (Brassica oleracea var Prince de Bretagne) buds
      were isolated according to the method described by Journet and Douce (E.P.
      Journet and R. Douce [1985] Plant Physiol 79: 458-467). Incubation of these
      plastids with various 14C-labeled compounds revealed that glucose-6-phosphate can
      act as a precursor for starch synthesis. However, significant rates
      (incorporation of 120 nmol glucose mg-1 protein h-1) could only be observed when
      both 3-phosphoglyceric acid and ATP were present as well. Starch synthesis in
      isolated plastids was strongly dependent upon the intactness of the organelle.
      The presence of a high-affinity ATP/ADP translocator with a Km for ATP of 12
      [mu]M was demonstrated by uptake experiments with [14C]ATP. ADP inhibited both
      ATP uptake and effector-stimulated starch synthesis. Effector-stimulated glucose
      6-phosphate-dependent starch synthesis was not significantly influenced by
      fructose-6-phosphate or 2-deoxyglucose-6-phosphate but was strongly inhibited by
      triose phosphate and inorganic phosphate. Starch synthesis was also inhibited by
      4,4[prime]-diisothio-cyanostilbene-2,2[prime]-disulfonate, which is known to be a
      potent inhibitor of the chloroplast phosphate translocator. The data presented
      here support the view that starch biosynthesis in heterotrophic tissues is
      powered by increasing levels of cytosolic 3-phosphoglyceric acid and ATP when
      glucose-6-phosphate is available.

PMID- 12231713
TI  - Purification and Characterization of the Voltage-Dependent Anion-Selective
      Channel Protein from Wheat Mitochondrial Membranes.
AB  - An approximately 29-kD protein was purified from the membrane fraction of wheat
      (Triticum aestivum cv Dganit) mitochondria by the utilization of standard liquid
      chromatography techniques. The protein, designated MmP29 for mitochondrial
      membrane protein having a molecular mass of approximately 29 kD, exhibited
      cationic properties in a buffering solution, adjusted to pH 7.5. This positive
      charge enabled its passage through a diethylaminoethyl column, without
      interaction with the positively charged matrix. Subsequently, this protein was
      separated from the remaining polypeptides by a preferential elution from a
      hydroxylapatite/celite mixed column. Reconstituted liposomes containing this
      protein were characterized as being permeable to 8-amino-naphthalene 1,3,6
      trisulfonic acid disodium salt (Mr 445) but non-permeable to dextran fluorescein
      (Mr 40,000). Additionally, MmP29 was inserted into planar phospholipid membranes,
      and anion-selective, voltage-dependent channels were demonstrated. All of the
      MmP29 properties mentioned highly resemble voltagedependent, anion-selective
      channel (VDAC) proteins, suggesting that MmP29 is the mitochondrial outer
      membrane VDAC protein of wheat.

PMID- 12231714
TI  - Inhibition of Sucrose:Sucrose Fructosyl Transferase by Cations and Ionic
      Strength.
AB  - Fructans are storage carbohydrates found in many temperate grasses. The first
      enzyme in the biosynthetic pathway of most fructans is sucrose:sucrose fructosyl
      transferase (SST). In this report, we demonstrate that K+ and ionic strength
      noncompetitively inhibit the activity of SST from wheat (Triticum aestivum L.)
      stems. The Ki for this inhibition is high, 122 mM, but in the range of
      concentrations of K+ found in the tissue (205-314 mM). Addition of KCl to the
      assay system had no effect on the pH optimum (5.5) or the Km for sucrose (266 mM)
      but reduced the Vmax. At equivalent ionic strengths, inhibition by choline
      chloride was about half that of KCl, indicating that inhibition by ionic strength
      might be responsible for approximately 50% of the KCl inhibition. Inhibition by
      LiCl and (NH4)2SO4 was similar to that by choline chloride. Soluble invertase
      activity found in the SST preparations was less sensitive to KCl and more
      sensitive to choline chloride than was SST. SST from barley (Hordeum vulgare L.)
      stems and leaves, as well as SST from leaves of orchardgrass (Dactylis
      glomerata), was also inhibited by KCl. SST from onion (Allium cepa L.) bulbs and
      asparagus (Asparagus officinalis L.) stems was not inhibited by KCl; thus,
      inhibition of activity by KCl is not a universal characteristic of SST from all
      sources.

PMID- 12231715
TI  - KDEL-Containing Auxin-Binding Protein Is Secreted to the Plasma Membrane and Cell
      Wall.
AB  - The auxin-binding protein ABP1 has been postulated to mediate auxin-induced
      cellular changes associated with cell expansion. This protein contains the
      endoplasmic reticulum (ER) retention signal, the tetrapeptide lysine-aspartic
      acid-glutamic acid-leucine (KDEL), at its carboxy terminus, consistent with
      previous subcellular fractionation data that indicated an ER location for ABP1.
      We used electron microscopic immunocytochemistry to identify the subcellular
      localization of ABP1. Using maize (Zea mays) coleoptile tissue and a black
      Mexican sweet (BMS) maize cell line, we found that ABP1 is located in the ER as
      expected, but is also on or closely associated with the plasma membrane and
      within the cell wall. Labeling of the Golgi apparatus suggests that the transport
      of ABP1 to the cell wall occurs via the secretory system. Inhibition of secretion
      of an ABP homolog into the medium of BMS cell cultures by brefeldin A, a drug
      that specifically blocks secretion, is consistent with this secretion pathway.
      The secreted protein was recognized by an anti-KDEL peptide antibody, strongly
      supporting the interpretation that movement of this protein out of the ER does
      not involve loss of the carboxy-terminal signal. Cells starved for 2,4
      dichlorophenoxyacetic acid for 72 h retained less ABP in the cell and secreted
      more of it into the medium. The significance of our observations is 2-fold. We
      have identified a KDEL-containing protein that specifically escapes the ER
      retention system, and we provide an explanation for the apparent discrepancy that
      most of the ABP is located in the ER, whereas ABP and auxin act at the plasma
      membrane.

PMID- 12231716
TI  - Germination and Dormancy of Abscisic Acid- and Gibberellin-Deficient Mutant
      Tomato (Lycopersicon esculentum) Seeds (Sensitivity of Germination to Abscisic
      Acid, Gibberellin, and Water Potential).
AB  - Germination responses of wild-type (MM), abscisic acid (ABA)-deficient (sitw),
      and gibberellin (GA)-deficient (gib-1) mutant tomato (Lycopersicon esculentum
      Mill. cv Moneymaker) seeds to ABA, GA4+7, reduced water potential ([psi]), and
      their combinations were analyzed using a population-based threshold model (B.R.
      Ni and K.J. Bradford [1992] Plant Physiol 98: 1057-1068). Among the three
      genotypes, sitw seeds germinated rapidly and completely in water, MM seeds
      germinated more slowly and were partially dormant, and gib-1 seeds did not
      germinate without exogenous GA4+7. Times to germination were inversely
      proportional to the differences between the external osmoticum, ABA, or GA4+7
      concentrations and the corresponding threshold levels that would either prevent
      ([psi]b, log[ABAb]) or promote (log[GAb]) germination. The sensitivity of
      germination to ABA, GA4+7, and [psi] varied widely among individual seeds in the
      population, resulting in a distribution of germination times. The rapid
      germination rate of sitw seeds was attributable to their low mean [psi]b (-1.17
      MPa). Postharvest dormancy in MM seeds was due to a high mean [psi]b (-0.35 MPa)
      and a distribution of [psi]b among seeds such that some seeds were unable to
      germinate even on water. GA4+7 (100 [mu]M) stimulated germination of MM and gib-1
      seeds by lowering the mean [psi]b to -0.75 MPa, whereas ABA inhibited germination
      of MM and sitw seeds by increasing the mean [psi]b. The changes in [psi]b were
      not due to changes in embryo osmotic potential. Rather, hormonal effects on
      endosperm weakening opposite the radicle tip apparently determine the threshold
      [psi] for germination. The analysis demonstrates that ABA- and GA-dependent
      changes in seed dormancy and germination rates, whether due to endogenous or
      exogenous growth regulators, are based primarily upon corresponding shifts in the
      [psi] thresholds for radicle emergence. The [psi] thresholds, in turn, determine
      both the rate and final extent of germination within the seed population.

PMID- 12231717
TI  - Growth and Nutrient Uptake by Barley (Hordeum vulgare L. cv Herta): Studies Using
      an N-(2-Hydroxyethyl)ethylenedinitrilotriacetic Acid-Buffered Nutrient Solution
      Technique (I. Zinc Ion Requirements).
AB  - The critical range of Zn2+ activity in nutrient solution required for optimum
      growth of barley (Hordeum vulgare L. cv Herta) was studied using the synthetic
      chelating agent N-(2-hydroxyethyl)ethylenedinitrilotriacetic acid to buffer
      micronutrient metal ions. The activity of Zn2+ was varied over a wide range from
      approximately 0.1 x 10-11 to 22 x 10-11 M Zn2+. The dry weight of barley shoots
      reached a maximum at Zn2+ activities above approximately 3 x 10-11 M and was
      clearly depressed when Zn2+ activities were below about 1 x 10-11 M. The
      relationship in shoots between dry weight and Zn concentrations supports the view
      that there is a critical Zn concentration of about 25 [mu]g g-1 dry weight in
      whole shoots of barley seedlings. When Zn2+ activities in solution were near or
      below approximately 3 x 10-11 M, barley shoots accumulated higher concentrations
      of P, Mn, Ca, Mg, and Na, whereas Cu concentrations were reduced. P and Mn began
      to accumulate in the shoots before differences in dry weights were apparent and
      provided the earliest index of Zn deficiency. In Zn-deficient roots,
      concentrations of Ca and Mg increased by 25 to 30%, and those of Fe and Mn more
      than doubled. Zn appears to play a special role in regulating uptake of several
      mineral nutrients in barley.

PMID- 12231718
TI  - Growth and Nutrient Uptake by Barley (Hordeum vulgare L. cv Herta): Studies Using
      an N-(2-Hydroxyethyl)ethylenedinitrilotriacetic Acid-Buffered Nutrient Solution
      Technique (II. Role of Zinc in the Uptake and Root Leakage of Mineral Nutrients).
AB  - Barley seedlings (Hordeum vulgare L. cv Herta) were grown in N-(2
      hydroxyethyl)ethylenedinitrilotriacetic acid-buffered nutrient solutions with or
      without adequate Zn supplies. Fifteen-d-old Zn-deficient seedlings contained
      higher concentrations of Mn, Ca, Mg, and P in their shoots and more Fe, Mn, Cu,
      K, Ca, and P in their roots than did similar Zn-adequate seedlings, confirming
      results reported in our companion study (W.A. Norvell and R.M. Welch [1993] Plant
      Physiol 101: 619-625). Zn-deficient roots leaked greater quantities of K, Mn, Cu,
      and Cl than did roots supplied adequately with Zn; they also leaked significant
      amounts of Zn even though the seedlings were not supplied Zn during growth.
      Calculated uptake rates of P, Mn, and Na were sharply reduced, but uptake rates
      of K and Mg were stimulated by increasing the Zn2+ activity in nutrient
      solutions. Intact roots of Zn-deficient seedlings contained lower concentrations
      of 5,5[prime] -dithio-bis(2-nitrobenzoic acid) reactive sulfhydryl groups in
      comparison to Zn-adequate roots. Apparently, Zn is required for the uptake and
      retention of several mineral nutrients by roots, possibly by playing a protective
      role in preventing the oxidation of sulfhydryl groups to disulfides in root-cell
      plasma membrane proteins involved in ion channel-gating phenomena.

PMID- 12231719
TI  - Effects of the Alkaloid Gramine on the Light-Harvesting, Energy Transfer, and
      Growth of Anabaena sp. (PCC 7119).
AB  - Long-term and short-term effects of gramine on cells of Anabaena sp. were
      studied. Culture death was observed after an initial growth in the presence of
      0.5 mM gramine, and lower concentrations decreased both the specific growth rate
      and the growth yield. Cultures showed a reduction in the chlorophyll content as
      well as an increase in the level of accessory pigments, which were proportional
      to the alkaloid concentration. When cultures were excited with green light in the
      presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea, the fluorescence spectra of
      the cells showed a shoulder at 685 nm related to the photosystem II (PSII)
      antennae emission. This band was reduced when gramine was present during the
      growth, suggesting that gramine suppresses the energy transfer between the
      phycobilisomes and PSII. At lethal concentrations for cellular growth, gramine
      suppressed immediately the photosynthetic oxygen production as well as the
      electron transport from H2O to p-benzoquinone. The influence of gramine on the
      PSII photochemical reactions was investigated by flash-induced fluorescence
      measurements, and the results suggest that the alkaloid could act as an electron
      donor to the PSII reaction center.

PMID- 12231720
TI  - Involvement of Abscisic Acid in Ethylene-Induced Cotyledon Abscission in Cotton
      Seedlings.
AB  - Cotton (Gossypium hirsutum L. cv LG102) seedlings raised from seeds exposed to
      100 [mu]M norflurazon (NFZ) during imbibition contained reduced levels of free
      abscisic acid (ABA) and were visibly achlorophyllous. Exposure of untreated
      cotton seedlings to ethylene concentrations >1 [mu]L/L for 24 h resulted in
      cotyledon abscission. In contrast, exposure of NFZ-treated seedlings to
      concentrations of ethylene [less than or equal to]50 [mu]L/L elicited no
      cotyledon abscission. Application of ABA, an ABA analog, or jasmonic acid to NFZ
      treated seedlings restored ethylene-induced abscission. Isolated cotyledonary
      node explants prepared from NFZ-treated seedlings exhibited an altered dose
      response pattern of ethylene-induced petiole abscission. Endogenous levels of
      free IAA were unaltered in NFZ-treated seedlings. Ethylene treatment (50 [mu]L/L,
      24 h) had no effect on free indoleacetic acid (IAA) levels in either control or
      NFZ-treated seedlings. Levels of conjugated (ester plus amide) IAA were
      substantially increased in NFZ-treated seedlings regardless of ethylene
      treatment. These results indicate that endogenous ABA plays an essential, but
      physiologically undefined, role in ethylene-induced cotyledon abscission in
      cotton.

PMID- 12231721
TI  - A Pea Plasma Membrane Protein Exhibiting Blue Light-Induced Phosphorylation
      Retains Photosensitivity following Triton Solubilization.
AB  - Phosphorylation of a polypeptide of approximately 120 kD in pea (Pisum sativum
      L.) plasma membranes in response to blue light has been shown to be involved in
      phototropic curvature, but the relationship of this protein to the kinase and
      photoreceptor acting upon it is uncertain. Using two-phase aqueous partitioning
      to isolate right-side-out plasma membrane vesicles, we have obtained evidence
      suggesting that the photoreceptor, kinase, and substrate are localized to the
      plasma membrane fraction. Latent phosphorylation accessible through Triton X-100
      or freeze/thaw treatments of purified plasma membrane vesicles indicates that at
      least the kinase moiety is present on the internal face of the plasma membrane.
      Effects of solubilization of vesicles on fluence-response characteristics and on
      phosphorylation levels provide evidence that the receptor, kinase, and protein
      substrate are present together in individual mixed detergent micelles, either as
      a stable complex or as domains of a single polypeptide. In vivo blue-light
      irradiation results in a small but significant decrease in mobility of the 120-kD
      phosphorylated protein on sodium dodecylsulfate gel electrophoresis. This
      mobility shift is evident on Coomassie-stained gels and on western blots probed
      with polyclonal antibodies raised against the 120-kD protein. Among the plasma
      membrane proteins bound to the reactive nucleotide analog
      fluorosulfonylbenzoyladenine (FSBA), a distinct protein band at 120 kD can be
      detected on blots probed with anti-FSBA antibodies. This band exhibits an in vivo
      light-dependent mobility shift identical to that observed for the protein band
      and antibodies specific for the 120-kD protein, implying that the 120-kD protein
      has an integral nucleotide binding site and consistent with the possibility that
      the substrate protein is also a kinase.

PMID- 12231722
TI  - Heme Inhibition of [delta]-Aminolevulinic Acid Synthesis Is Enhanced by
      Glutathione in Cell-Free Extracts of Chlorella.
AB  - In plants, algae, and many bacteria, the heme and chlorophyll precursor, [delta]
      aminolevulinic acid (ALA), is synthesized from glutamate in a reaction involving
      a glutamyl-tRNA intermediate and requiring ATP and NADPH as cofactors. In
      particulate-free extracts of algae and chloroplasts, ALA synthesis is inhibited
      by heme. Inclusion of 1.0 mM glutathione (GSH) in an enzyme and tRNA extract,
      derived from the green alga Chlorella vulgaris, lowered the concentration of heme
      required for 50% inhibition approximately 10-fold. The effect of GSH could not be
      duplicated with other reduced sulfhydryl compounds, including mercaptoethanol,
      dithiothreitol, and cysteine, or with imidazole or bovine serum albumin, which
      bind to heme and dissociate heme dimers. Absorption spectroscopy indicated that
      heme was fully reduced in incubation medium containing dithiothreitol, and
      addition of GSH did not alter the heme reduction state. Oxidized GSH was as
      effective in enhancing heme inhibition as the reduced form. Co-protoporphyrin IX
      inhibited ALA synthesis nearly as effectively as heme, and 1.0 mM GSH lowered the
      concentration required for 50% inhibition approximately 10-fold. Because GSH did
      not influence the reduction state of heme in the incubation medium, and because
      GSH could not be replaced by other reduced sulfhydryl compounds or ascorbate, the
      effect of GSH cannot be explained by action as a sulfhydryl protectant or heme
      reductant. Preincubation of enzyme extract with GSH, followed by rapid gel
      filtration, could not substitute for inclusion of GSH with heme during the
      reaction. The results suggest that GSH must specifically interact with the enzyme
      extract in the presence of the inhibitor to enhance the inhibition.

PMID- 12231724
TI  - Strategies for Control of Fungal Diseases with Transgenic Plants.

PMID- 12231723
TI  - Decreased Membrane Integrity in Aging Typha latifolia L.Pollen (Accumulation of
      Lysolipids and Free Fatty Acids).
AB  - Aging of cattail (Typha latifolia L.) pollen was studied at 24[deg]C under
      conditions of 40 and 75% relative humidity (RH). The decline of viability
      coincides with increased leakage at imbibition; both processes develop much
      faster at the higher humidity condition. During aging phospholipids are
      deesterified and free fatty acids (FFAs) and lysophospholipids (LPLs) accumulate,
      again, much more rapidly at 75% RH than at 40% RH. The fatty acid composition of
      the remaining phospholipids hardly changes during aging, which suggests limited
      involvement of lipid peroxidation in the degradation process. Tests with
      phospholipase A2 revealed that the saturated fatty acids occur at the sn-1
      position of the glycerol backbone of the phospholipids. The fatty acid
      composition of the LPLs is similar to that of the phospholipids from which they
      were formed, indicating that the deesterification occurs at random. This favors
      involvement of free radicals instead of phospholipases in the deesterification
      process. Liposome studies were carried out to characterize components in the
      lipid fraction that might account for the leakage associated with aging.
      Entrapped carboxyfluorescein leaked much more from liposomes when they were
      partly made up from total lipids from aged pollen than from nonaged pollen. The
      components causing the leakage were found in both the polar and the neutral lipid
      fractions. Further purification and subsequent interchanging of the FFAs and LPLs
      between extracts from aged and nonaged pollen revealed that in neutral lipid
      extracts the FFAs are entirely responsible for the leakage, whereas in the
      phospholipid fraction the LPLs are largely responsible for the leakage. The
      leakage from the liposomes is not caused by fusion. We suggest that the observed
      loss of viability and increased leakage during aging are due to the nonenzymic
      accumulation of FFAs and LPLs in the pollen membranes.

PMID- 12231725
TI  - The Anticyclic Timing of Leaf Senescence in the Parasitic Plant Viscum album Is
      Closely Correlated with the Selective Degradation of Sulfur-Rich Viscotoxins.
AB  - Leaf senescence and abscission have been studied in the semi-parasitic plant
      mistletoe (Viscum album). Leaf senescence and abscission occur in the summer,
      when the metabolic activity of the host has reached its maximum. In contrast with
      their hosts, mistletoes selectively degrade only one major leaf protein during
      leaf senescence, the sulfur-rich viscotoxin, whereas most of the remaining leaf
      proteins are lost during abscission. The changes in viscotoxin content are
      paralleled by changes in the concentration of the corresponding mRNA. Shortly
      before the onset of leaf senescence, the mRNA for viscotoxin has disappeared from
      the leaves. The anticyclic timing of leaf senescence and the degradation of only
      one major leaf protein seems to reflect an adaptation of the parasite to its
      habitat.

PMID- 12231726
TI  - Transformation and Regeneration of Two Cultivars of Pea (Pisum sativum L.).
AB  - A reproducible transformation system was developed for pea (Pisum sativum L.)
      using as explants sections from the embryonic axis of immature seeds. A construct
      containing two chimeric genes, nopaline synthase-phosphinothricin acetyl
      transferase (bar) and cauliflower mosaic virus 35S-neomycin phosphotransferase
      (nptII), was introduced into two pea cultivars using Agrobacterium tumefaciens
      mediated transformation procedures. Regeneration was via organogenesis, and
      transformed plants were selected on medium containing 15 mg/L of
      phosphinothricin. Transgenic peas were raised in the glasshouse to produce
      flowers and viable seeds. The bar and nptII genes were expressed in both the
      primary transgenic pea plants and in the next generation progeny, in which they
      showed a typical 3:1 Mendelian inheritance pattern. Transformation of regenerated
      plants was confirmed by assays for neomycin phosphotransferase and
      phosphinothricin acetyl transferase activity and by northern blot analyses.
      Transformed plants were resistant to the herbicide Basta when sprayed at rates
      used in field practice.

PMID- 12231727
TI  - Expression of the le Mutation in Young Ovaries of Pisum sativum and Its Effect on
      Fruit Development.
AB  - The effect of the le mutation on the growth and gibberellin (GA) content of
      developing fruits was investigated using the near-isogenic lines of Pisum sativum
      L. 205+ (LeLe) and 205- (lele). Although stem elongation is known to be reduced
      in 205- plants by approximately 65%, the growth of pods and seeds was unaffected
      by the le mutation. GA1, GA3, and GA20 stimulated parthenocarpic development of
      unpollinated ovaries on both 205+ and 205- plants. GA20 was less active on 205-
      ovaries than on 205+, whereas GA1 had similar, high activity in both lines. The
      activity of GA3 was even higher than that of GA1 in both lines. Decapitation of
      205+ plants induced parthenocarpic development of unpollinated ovaries, but this
      treatment was much less effective on 205- plants. The contents of GA1 and GA8 in
      entire ovaries 6 d after anthesis, as well as in the pod and fertilized ovules,
      were substantially lower in 205- than in 205+ plants, whereas the reverse was
      true for the levels of GA20 and GA29. These results suggest that 3[beta]
      hydroxylation of GA20 to GA1 is reduced in ovaries as well as in vegetative
      tissues. Thus, the le mutation appears to be expressed in young reproductive
      organs of the 205- line, even though it does not affect the fruit phenotype.
      Because the content of GA3 in the ovary was similar in the two lines, one
      explanation for the normal fruit size in the 205- line is that GA3 is the native
      regulator of pod growth. Alternatively, sufficient GA1 may still be produced in
      205- fruits to maintain normal pod growth.

PMID- 12231728
TI  - Essential Arginyl Residue at the Active Site of Pyrophosphate:Fructose 6
      Phosphate 1-Phosphotransferase from Potato (Solanum tuberosum) Tuber.
AB  - The aim of this work was to test the proposal that the active site of
      pyrophosphate:fructose 6-phosphate 1-phosphotransferase (PFP) contains an
      essential arginyl residue. Enzyme activity was inhibited equally in the
      glycolytic and gluconeogenic directions by arginine-modifying reagents. The
      second-order rate constants for 2,3-butanedione and phenylglyoxal were 13.1 [plus
      or minus] 0.45 and 55.3 [plus or minus] 1.3 M-1 min-1, respectively. The
      corresponding values for the kinetic order of inactivation by these modifying
      reagents were 0.84 [plus or minus] 0.049 for 2,3-butanedione and 0.89 [plus or
      minus] 0.052 for phenylglyoxal. The substrates, fructose 6-phosphate and
      pyrophosphate, and a range of substrate analogs protected the enzyme from
      inactivation by 2,3-butanedione. These data suggest that modification of no more
      than one arginyl residue at, or close to, the active site is required to inhibit
      the enzyme. This result supports the proposal that the active site of PFP in
      plants is equivalent to that of the bacterial ATP-phosphofructokinase (S.M.
      Carlisle, S.D. Blakeley, S.M. Hemmingsen, S.J. Trevanion, T. Hiyoshi, N.J.
      Kruger, and D.T. Dennis [1990] J Biol Chem 265: 18366-18371).

PMID- 12231729
TI  - Plastid Genes Encoding the Transcription/Translation Apparatus Are Differentially
      Transcribed Early in Barley (Hordeum vulgare) Chloroplast Development (Evidence
      for Selective Stabilization of psbA mRNA).
AB  - Chloroplast genomes encode rRNAs, tRNAs, and proteins involved in transcription,
      translation, and photosynthesis. The expression of 15 plastid genes representing
      each of these functions was quantitated during chloroplast development in barley
      (Hordeum vulgare). The transcription of all plastid genes increased during the
      initial phase of chloroplast development and then declined during chloroplast
      maturation. RNAs corresponding to rpoB- rpoC1-rpoC2, which encode subunits of a
      plastid RNA polymerase, and rps16, which encodes a ribosomal protein, reached
      maximal abundance early in chloroplast development prior to genes encoding
      subunits of the photosynthetic apparatus (rbcL, atpB, psaA, petB). Transcription
      of rpoB as well as 16S rRNA, trnfM-trnG, and trnK was high early in chloroplast
      development and declined 10-fold relative to rbcL transcription during
      chloroplast maturation. RNA hybridizing to psbA and psbD, genes encoding reaction
      center proteins of photosystem II, was differentially maintained in mature
      chloroplasts of illuminated barley. Differential accumulation of psbD mRNA
      relative to rbcL mRNA was due to light-stimulated transcription of psbD. In
      contrast, enhanced levels of psbA mRNA in mature chloroplasts were due primarily
      to selective stabilization of the psbA mRNA. These data document dynamic
      modulation of plastid gene transcription and mRNA stability during barley
      chloroplast development.

PMID- 12231730
TI  - Assay of Proton-Coupled Glycolate and D-Glycerate Transport into Chloroplast
      Inner Envelope Membrane Vesicles by Stopped-Flow Fluorescence.
AB  - The transport of glycolate and D-glycerate across the inner envelope membrane of
      intact chloroplasts is rapid and mediated by a translocator with proton/substrate
      symport activity. The true initial rate of glycolate or D-glycerate transport
      could not be measured by conventional methods. To resolve the initial rates of
      glycolate and D-glycerate transport, a stopped-flow fluorescence assay was
      developed that allows the indirect observation of transport from about 4 ms after
      mixing. Inner envelope vesicles from pea (Pisum sativum) or spinach (Spinacia
      oleracea) chloroplasts were loaded with the fluorescent pH indicator pyranine (8
      hydroxypyrene-1,3,6-trisulfonic acid) by a freeze-thaw sonication protocol. A
      rapid quenching of pyranine fluorescence was detected after mixing the vesicles
      with either glycolate or D-glycerate. This quenching was the result of
      acidification of the interior of the vesicles. D-Glycerate- or glycolate-induced
      acidification displayed saturation kinetics and was inhibited by pretreatment of
      the vesicles with N-ethylmaleimide. D-Glycerate was more effective than L
      glycerate in causing the pH decrease. Also, L-mandelate inhibited D-glycerate
      induced acidification much more strongly than D-mandelate. The glycolate/D
      glycerate-induced pH decrease is consistent with glycolate/D-glycerate
      translocator activity. The assay was placed on a quantitative basis by converting
      fluorescence changes to pH and measuring the internal buffering capacity of the
      vesicles. The rates of transport across the inner envelope membrane were
      estimated to be as fast, if not faster, than those of transport in intact
      chloroplasts.

PMID- 12231731
TI  - Alfalfa (Medicago sativa L.) Root Exudates Contain Isoflavonoids in the Presence
      of Rhizobium meliloti.
AB  - Root exudates of alfalfa (Medicago sativa L.) inoculated with symbiotic Rhizobium
      meliloti bacteria contained three isoflavonoids that were not found in exudates
      of uninoculated plants. Data from proton nuclear magnetic resonance, mass
      spectrometry, and ultraviolet-visible absorbance analyses indicated that root
      exudates of inoculated plants contained aglycone and glycoside forms of the
      phytoalexin medicarpin and a formononetin-7-O-(6"-O-malonylglycoside), a
      conjugated form of the medicarpin precursor formononetin. The medicarpin
      molecules did not induce nod gene transcription in R. meliloti, but the
      formononetin-7-O-(6"-O-malonylglycoside) induced nod genes regulated by both
      NodD1 and NodD2 proteins in R. meliloti. Hydrolysis of either the malonyl or the
      glycosyl linkage from the formononetin conjugate eliminated nod gene-inducing
      activity. The nod gene-inducing activity of crude root exudates was increased 200
      and 65% upon inoculation with R. meliloti or R. leguminosarum bv phaseoli,
      respectively. When root exudate from uninoculated alfalfa was incubated with R.
      meliloti, high performance liquid chromatography analyses showed no evidence that
      bacterial metabolism produced medicarpin. These results indicate that alfalfa
      responds to symbiotic R. meliloti by exuding a phytoalexin normally elicited by
      pathogens and that the microsymbiont can use a precursor of the phytoalexin as a
      signal for inducing symbiotic nod genes.

PMID- 12231732
TI  - Photosynthetic Characteristics of Segregates from Hybrids between Flaveria
      brownii (C4 Like) and Flaveria linearis (C3-C4).
AB  - Characteristics related to C4 photosynthesis were studied in reciprocal F1
      hybrids and F2 plants from Flaveria brownii (C4 like) and Flaveria linearis (C3
      C4). The reciprocal F1 plants differed in 13C/12C ratios of leaves and the
      percentage of 14C initially incorporated into C4 acids, being more like the
      pollen parents in these traits. They did not differ in apparent photosynthesis or
      in O2 inhibition of apparent photosynthesis and differed only slightly in CO2
      compensation concentration at 175 [mu]mol quanta m-2 s-1 and 400 mL L-1 O2. The
      13C/12C ratios of 78 F2 progeny from the two F1 plants exhibited a normal
      distribution centered between those of the parents, with a few values slightly
      higher and lower than the parents. Apparent photosynthesis at 130 [mu]L L-1 CO2
      and inhibition of photosynthesis by O2 was nearly normally distributed in the F2
      population, but no values for F2 plants approached those for F. brownii (15.4
      [mu]mol m-2 s-1 and 7.8%, respectively). Distribution of the CO2 compensation
      concentration measured at 1000 [mu]mol quanta m-2 s-1 and 400 mL L-1 of O2 in the
      F2 population was skewed toward F. brownii with 72% of the progeny having values
      <9 [mu]L of CO2 L-1 compared to 1.5 and 27.2 [mu]L L-1 for F. brownii and F.
      linearis, respectively. Correlations among traits of F2 plants were low
      (coefficients of 0.30 to -0.49), indicating that the C4- related traits are not
      closely linked in segregating populations. Plants in the F2 population selected
      for high or low apparent photosynthesis at 130 [mu]L of CO2 L-1 (six each) did
      not rank consistently high or low for 13C/12C ratios, O2 inhibition of apparent
      photosynthesis, CO2 compensation concentration, or activities of
      phosphoenolpyruvate carboxylase or NADP-malic enzyme. This study confirms results
      of earlier work that indicates independent segregation of C4 traits and also
      shows that the C4-like parental type can be recovered, at least for some
      characteristics (13C/12C ratio), in segregating populations. Recovery of fully
      functional C4 plants awaits further experimentation with C4 x C3 or C4 x C3-C4
      hybrid plants that produce fertile progeny.

PMID- 12231733
TI  - Low Temperature Induces the Accumulation of Alcohol Dehydrogenase mRNA in
      Arabidopsis thaliana, a Chilling-Tolerant Plant.
AB  - mRNA encoding alcohol dehydrogenase (ADH) increases in etiolated seedlings and
      leaves of Arabidopsis thaliana (L.) Heynh. upon exposure to low temperature. The
      analysis of this response after water stress and abscisic acid (ABA) treatments
      in Arabidopsis wild type and ABA-deficient and -insensitive mutants indicates
      that cold accumulation of ADH mRNA could be induced by both anaerobic metabolism
      and increase of ABA concentration resulting from low temperature exposure. By
      using one Arabidopsis ADH null mutant, we show that ADH activity is not required
      for successful development of freezing tolerance in this species.

PMID- 12231734
TI  - Mutants of Arabidopsis thaliana Capable of Germination under Saline Conditions.
AB  - Three mutant strains of Arabidopsis thaliana var Columbia were selected for their
      ability to germinate in elevated concentrations of NaCl. They were not more
      tolerant than wild type at subsequent development stages. Wild-type strains could
      not germinate at concentrations > 125 mM NaCl. Two of mutant strains, RS17 and
      RS20, could withstand up to 225 mM, whereas RS19 was resistant to 175 mM. The RS
      mutants could also germinate under even lower osmotic potentials imposed by high
      concentrations of exogenous mannitol (550 mM), whereas the effects of elevated
      levels of KCl, K2SO4, and LiCl were similar among the mutants and wild type.
      Therefore, the mutants are primarily osmotolerant, but they also possess a degree
      of ionic tolerance for sodium. Sodium and potassium contents of seeds exposed to
      high salinities indicated that the NaCl-tolerant mutants absorbed more of these
      respective cations during imbibition. These higher internal concentrations of
      potassium and sodium could contribute to the osmotic adjustment of the
      germinating seeds to the low osmotic potential of the external medium. Genetic
      analysis of F1 and F2 progeny of outcrosses suggest that the salt-tolerant
      mutations are recessive and that they define three complementation groups.

PMID- 12231735
TI  - Stress Responses in Alfalfa (Medicago sativa L.) (XIV. Changes in the Levels of
      Phenylpropanoid Pathway Intermediates in Relation to Regulation of L
      Phenylalanine Ammonia-Lyase in Elicitor-Treated Cell-Suspension Cultures).
AB  - We have used high-resolution gas chromatography to determine the levels of trans
      cinnamic acid (CA) and trans-4-coumaric acid (4CA) in alfalfa (Medicago sativa
      L.) cell-suspension cultures to address the role of these phenylpropanoid pathway
      intermediates as potential negative regulators of phenylalanine ammonia-lyase
      (PAL) in vivo. Exogenous addition of CA to elicitor-treated cultures resulted in
      rapid increases in endogenous CA, 4CA, and CA-conjugate levels associated with
      inhibition of the appearance of PAL transcripts. Treatment of elicited cultures
      with [alpha]-aminooxy-[beta]-phenylpropionic acid (AOPP), a potent and specific
      inhibitor of PAL activity in vivo, resulted in reductions of CA and 4CA, with
      concomitant increases in PAL transcripts and extractable enzyme activity. In
      contrast, treatment with tetcyclacis, an inhibitor of CA 4-hydroxylase, resulted
      in increased CA and CA-conjugate levels, decreased 4CA levels, and decreased PAL
      transcript levels and enzyme activity. In tetcyclasis-treated cells, the
      inhibition of PAL transcript appearance preceded the increase in the levels of
      free CA and its conjugates. In elicited cells in which the phenylpropanoid
      pathway was not perturbed by metabolic inhibitors, PAL transcripts accumulated
      rapidly and transiently, beginning to decline by 2 h postelicitation. Changes in
      levels of total free or conjugated CA or 4CA did not consistently correlate with
      these changes in transcript levels. We propose that regulation of PAL transcript
      levels by endogenous phenylpropanoid pathway intermediates could involve
      compartmentalized pools that may exist because of the microsomal localization of
      cinnamic acid 4-hydroxylase.

PMID- 12231736
TI  - Only Specific Tobacco (Nicotiana tabacum) Chitinases and [beta]-1,3-Glucanases
      Exhibit Antifungal Activity.
AB  - Different isoforms of chitinases and [beta]-1,3-glucanases of tobacco (Nicotiana
      tabacum cv Samsun NN) were tested for their antifungal activities. The class I,
      vacuolar chitinase and [beta]-1,3-glucanase isoforms were the most active against
      Fusarium solani germlings, resulting in lysis of the hyphal tips and in growth
      inhibition. In additon, we observed that the class I chitinase and [beta]-1,3
      glucanase acted synergistically. The class II isoforms of the two hydrolases
      exhibited no antifungal activity. However, the class II chitinases showed limited
      growth inhibitory activity in combination with higher amounts of class I [beta]
      1,3-glucanase. The class II [beta]-1,3-glucanases showed no inhibitory activity
      in any combination. In transgenic tobacco plants producing modified forms of
      either a class I chitinase or a class I [beta]-1,3-glucanase, or both, these
      proteins were targeted extracellularly. Both modified proteins lack their C
      terminal propeptide, which functions as a vacuolar targeting signal.
      Extracellular targeting had no effect on the specific activities of the chitinase
      and [beta]-1,3-glucanase enzymes. Furthermore, the extracellular washing fluid
      (EF) from leaves of transgenic plants expressing either of the secreted class I
      enzymes exhibited antifungal activity on F. solani germlings in vitro comparable
      to that of the purified vacuolar class I proteins. Mixing EF fractions from these
      plants revealed synergism in inhibitory activity against F. solani; the mixed
      fractions exhibited inhibitory activity similar to that of EF from plants
      expressing both secreted enzymes.

PMID- 12231737
TI  - Ammonia Assimilation in Zea mays L. Infected with a Vesicular-Arbuscular
      Mycorrhizal Fungus Glomus fasciculatum.
AB  - To investigate nitrogen assimilation and translocation in Zea mays L. colonized
      by the vesicular-arbuscular mycorrhizal (VAM) fungus Glomus fasciculatum (Thax.
      sensu Gerd.), we measured key enzyme activities, 15N incorporation into free
      amino acids, and 15N translocation from roots to shoots. Glutamine synthetase and
      nitrate reductase activities were increased in both roots and shoots compared
      with control plants, and glutamate dehydrogenase activity increased in roots
      only. In the presence of [15N]ammonium, glutamine amide was the most heavily
      labeled product. More label was incorporated into amino acids in VAM plants. The
      kinetics of 15N labeling and effects of methionine sulfoximine on distribution of
      15N-labeled products were entirely consistent with the operation of the glutamate
      synthase cycle. No evidence was found for ammonium assimilation via glutamate
      dehydrogenase. 15N translocation from roots to shoots through the xylem was
      higher in VAM plants compared with control plants. These results establish that,
      in maize, VAM fungi increase ammonium assimilation, glutamine production, and
      xylem nitrogen translocation. Unlike some ectomycorrhizal fungi, VAM fungi do not
      appear to alter the pathway of ammonium assimilation in roots of their hosts.

PMID- 12231738
TI  - Sunflower (Helianthus annuus L.) Pathogenesis-Related Proteins (Induction by
      Aspirin (Acetylsalicylic Acid) and Characterization).
AB  - Sunflower leaf discs floated on a solution containing aspirin (acetylsalicylic
      acid) produced a set of new proteins extractable at pH 5.2 and excreted into the
      intercellular space. More than 80% of the proteins found in the intercellular
      fluids of induced leaf discs have been identified as pathogenesis-related (PR)
      proteins by their immunological relationship with tobacco PR proteins. Members of
      the four major classes of PR proteins have been characterized. Sunflower PR
      proteins of type 1 (PR1) and of type 3 (PR3) were found to have acidic
      isoelectric points, whereas the induced PR protein of type 2 (PR2) had a basic
      isoelectric point. Members of the type 5 PR proteins (PR5), known in tobacco as
      thaumatin-like proteins, showed a more complex pattern. Multiple sunflower PR5
      isomers of similar molecular weight but of different isoelectric points were
      excreted from the cells in response to the aspirin treatment. PR2 and PR3
      proteins were found at very low basal levels in untreated leaves, whereas PR1 and
      PR5 proteins could not be detected at all in the same extracts. Glucanase and
      chitinase activities were always associated with PR2 and PR3 proteins in
      partially purified sunflower extracts. All of these data indicate that, in
      response to aspirin treatment, sunflower plants produce a complete set of PR
      proteins characterized by an apparently exclusively extracellular localization.

PMID- 12231739
TI  - Development of Limit Dextrinase in Germinated Barley (Hordeum vulgare L.)
      (Evidence of Proteolytic Activation).
AB  - Barley (Hordeum vulgare L.) that had been malted for 5 d developed only a small
      amount of bound (inactive) limit dextrinase, and very little free (active) enzyme
      was detected. Continuation of malting for up to 10 d only slightly increased the
      amount of both bound and free forms. Grain grown under conditions of ample
      moisture (wet grown) for 5 d produced a much higher amount of bound enzyme but a
      similarly low amount of free enzyme compared to malting conditions. After 10 d of
      growth there was a decrease in the amount of bound enzyme and a large increase in
      the amount of free enzyme, such that almost all of the enzyme was present in the
      free form. A more detailed study of limit dextrinase development in wet-grown
      grains revealed that a bound form was rapidly produced soon after germination.
      Five to 6 d after germination the amount of bound enzyme decreased rapidly and a
      very low amount was found in grains 9 d after germination. Meanwhile, a free form
      appeared slightly later and its initial rate of development was slow. At about 5
      d after germination, precisely when the bound enzyme began to decrease, the free
      form increased rapidly, so that by 9 d after germination nearly all the enzyme
      was in the free form. The release of bound limit dextrinase in vitro occurred by
      proteolytic modification through the action of cysteine proteinases that were
      kept active or activated by the presence of reduced thiols in the extraction
      medium. The presence of cysteine proteinases was confirmed by inhibition studies
      using the inhibitors iodoacetamide, N-ethylmaleimide, antipain, and leupeptin. In
      addition, most of the bound form of limit dextrinase was soluble in 0.2 M sodium
      acetate buffer (pH 5.0) following extraction at 30[deg]C for 16 h and
      centrifugation at 3000g.

PMID- 12231740
TI  - Regulatory Phosphorylation of C4 Phosphoenolpyruvate Carboxylase (A Cardinal
      Event Influencing the Photosynthesis Rate in Sorghum and Maize).
AB  - C4 leaf phosphoenolpyruvate carboxylase (PEPC; EC 4.1.1.31) is subject to a
      day/night regulatory phosphorylation cycle. By using the cytoplasmic protein
      synthesis inhibitor cycloheximide (CHX), we previously reported that the
      reversible in vivo light activation of the C4 PEPC protein-serine kinase requires
      protein synthesis. In the present leaf gas-exchange study, we have examined how
      and to what extent the CHX-induced inhibition of PEPC protein kinase
      activity/PEPC phosphorylation in the light influences C4 photosynthesis. Detached
      Sorghum vulgare and maize (Zea mays) leaves fed 10 [mu]M CHX showed a gradual but
      marked decrease in photosynthetic CO2 assimilation capacity. A series of control
      experiments designed to assess deleterious secondary effects of the inhibitor
      established that this reduction in C4 leaf CO2 assimilation was not due to (a) an
      increased stomatal resistance to CO2 diffusion, (b) a decrease in the activation
      state of other photoactivated C4 cycle enzymes, and (c) a perturbation of the
      Benson-Calvin C3 cycle, as evidenced by the absence of an inhibitory effect of
      CHX on leaf photosynthesis by a C3 grass (Triticum aestivum). It is notable that
      the CHX-induced decrease in CO2 assimilation by illuminated Sorghum leaves was
      highly correlated with a decrease in the apparent phosphorylation status of PEPC
      and a concomitant change in carbon isotope discrimination consistent with a shift
      from a C4 to a C3 mode of leaf CO2 fixation. These collective findings indicate
      that the light-dependent activation of the PEPC protein-serine kinase and the
      resulting phosphorylation of serine-8 or serine-15 in Sorghum or maize PEPC,
      respectively, are fundamental regulatory events that influence leaf C4
      photosynthesis in vivo.

PMID- 12231741
TI  - Companion-Cell Specific Localization of Sucrose Synthase in Zones of Phloem
      Loading and Unloading.
AB  - An immunohistochemical approach was used in maize (Zea mays) and citrus (Citrus
      paradisi) to address the previously noted association between sucrose synthase
      and vascular bundles and to determine the localization of the low but detectable
      levels of sucrose synthase that remain in leaves after the import-export
      transition. Sucrose synthase protein was immunolocalized at the light microscope
      level using paraffin sections reacted with rabbit sucrose synthase polyclonal
      antisera and gold-conjugated goat anti-rabbit immunoglobulin G. Immunolabel was
      specifically observed in phloem companion cells of minor and intermediate veins
      in mature leaves of both species. Similar localization was apparent in the midrib
      of mature citrus leaves, with additional labeling in selected files of phloem
      parenchyma cells. A clear companion-cell specificity was evident in the phloem
      unloading zone of citrus fruit, where high activity of sucrose synthase has been
      demonstrated in vascular bundles during periods of rapid import. Sucrose synthase
      protein was not associated with adjacent cells surrounding the vascular strands
      in this tissue. The companion-cell specificity of sucrose synthase in phloem of
      both importing and exporting structures of these diverse species implies that
      this may be a widespread association and underscores its potential importance to
      the physiology of vascular bundles.

PMID- 12231742
TI  - Rapid, Blue-Light-Induced Acidifications at the Surface of Ectocarpus and Other
      Marine Macroalgae.
AB  - In most brown algae, photosynthesis saturated with red light can be stimulated by
      continuous blue light. Pulses of blue light lead to transient increases in
      photosynthetic rate. When a CO2-sensitive electrode was used, occasionally blue
      light was observed to cause an apparent increase of CO2 instead of the expected
      decrease. This was changed by buffering the seawater medium and, under these
      conditions, blue light caused stimulation of CO2 consumption. These results led
      to investigations of blue-light-dependent pH changes at the outer surface of the
      plants. Shifts of the pH were recorded in the presence of the photosynthetic
      inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea. In all brown algae tested and
      in the green algae Ulva and Enteromorpha, blue-light pulses caused transient
      acidification of 0.03 to 0.18 pH units, depending on the species. The kinetics
      showed lag phases of a few seconds and the minimum was reached after 5 to 9 min.
      Fluence response relationships indicated that the sensitivity (threshold) to blue
      light was very similar in all species. The responses in Ectocarpus changed with
      time, and about 5 h after the beginning of red light or darkness, a second
      component became evident, which peaked 20 min after the blue-light pulse. The
      refractory period of the whole system was about 3 h in Ectocarpus. The blue-light
      dependent pH changes show striking similarities to those of higher plant guard
      cells, and it is possible that similar responses may occur in other tissues of
      higher plants. In red algae, however, no blue-light-dependent acidifications
      could be detected. The possible role of the observed pH shifts in a mechanism of
      CO2 acquisition is discussed.

PMID- 12231743
TI  - Characterization and Solubilization of Kaurenoic Acid Hydroxylase from Gibberella
      fujikuroi.
AB  - A key step in gibberellin biosynthesis is the conversion of ent-kaurenoic acid to
      ent-7[alpha]-hydroxykaurenoic acid, mediated by the enzyme kaurenoic acid
      hydroxylase. A cell-free system obtained from Gibberella fujikuroi (Saw.) Wr. was
      used to characterize kaurenoic acid hydroxylase activity. Microsomal preparations
      from disrupted fungal cells, in the presence of O2 and NADPH, converted [17
      14C]ent-kaurenoic acid to oxidation products that were separated by high
      performance liquid chromatography and identified as ent-7[alpha]-hydroxykaurenoic
      acid and gibberellin A14 by combined gas chromatography-mass spectrometry. Flavin
      adenine dinucleotide and the chloride salts of several monovalent cations
      stimulated the conversion of ent-kaurenoic acid to these products, whereas CO and
      a number of known inhibitors of cytochrome P-450-dependent reactions, including
      paclobutrazol, tetcyclacis, BAS 111.W, flurprimidol, triarimol, metyrapone, and 1
      phenylimida-zole, significantly reduced kaurenoic acid hydroxylase activity.
      Kaurenoic acid hydroxylase was solubilized from fungal microsomes by treatment
      with 1 M KCl. The properties of the enzyme noted above suggest that kaurenoic
      acid hydroxylase from G. fujikuroi is a cytochrome P-450-dependent monooxygenase.

PMID- 12231744
TI  - Monoclonal Antibodies to the [alpha]- and [beta]-Subunits of the Plant
      Mitochondrial F1-ATPase.
AB  - We have generated nine monoclonal antibodies against subunits of the maize (Zea
      mays L.) mitochondrial F1-ATPase. These monoclonal antibodies were generated by
      immunizing mice against maize mitochondrial fractions and randomly collecting
      useful hybridomas. To prove that these monoclonal antibodies were directed
      against ATPase subunits, we tested their cross-reactivity with purified F1-ATPase
      from pea cotyledon mitochondria. One of the antibodies ([alpha]-ATPaseD) cross
      reacted with the pea F1-ATPase [alpha]-subunit and two ([beta]-ATPaseD and [beta]
      ATPaseE) cross-reacted with the pea F1-ATPase [beta]-subunit. This established
      that, of the nine antibodies, four react with the maize [alpha]-ATPase subunit
      and the other five react with the maize [beta]-ATPase subunit. Most of the
      monoclonal antibodies cross-react with the F1-ATPase from a wide range of plant
      species. Each of the four monoclonal antibodies raised against the [alpha]
      subunit recognizes a different epitope. Of the five [beta]-subunit antibodies, at
      least three different epitopes are recognized. Direct incubation of the
      monoclonal antibodies with the F1-ATPase failed to inhibit the ATPase activity.
      The monoclonal antibodies [alpha]-ATPaseD and [beta]-ATPaseD were bound to
      epoxide-glass QuantAffinity beads and incubated with a purified preparation of
      pea F1-ATPase. The ATPase activity was not inhibited when the antibodies bound
      the ATPase. The antibodies were used to help map the pea F1-ATPase subunits on a
      two-dimensional map of whole pea cotyledon mitochondrial protein. In addition,
      the antibodies have revealed antigenic similarities between various isoforms
      observed for the [alpha]- and [beta]-subunits of the purified F1-ATPase. The
      specificity of these monoclonal antibodies, along with their cross-species
      recognition and their ability to bind the F1-ATPase without inhibiting enzymic
      function, makes these antibodies useful and invaluable tools for the further
      purification and characterization of plant mitochondrial F1-ATPases.

PMID- 12231745
TI  - Estimation and Analysis of Cucumber (Cucumis sativus L.) Leaf Cellular Heat
      Sensitivity.
AB  - Triphenyl tetrazolium chloride (TTC) reduction by cucumber (Cucumis sativus L. cv
      Poinsett 76 and cv Ashley) leaf discs was used as a viability assay to examine
      the effect of temperature pretreatment on the tissue response to acute
      hyperthermia. Semi-logarithmic plots of TTC reduction as a function of incubation
      time at different temperatures from 40 to 60[deg]C resembled the heat survival
      curves of animal cells. Heat inactivation rates were obtained and subjected to
      "quasi" Arrhenius analyses by analytical methods derived from the animal studies.
      The Arrhenius plots of TTC reduction rates for cv Ashley leaf discs preincubated
      at 25 or 37[deg]C and for cv Poinsett 76 preincubated at 37[deg]C were linear
      with the same activation energy (Ea) of about 80 kcal mol-1. The Arrhenius plot
      of cv Poinsett 76 preincubated at 25[deg]C was nonlinear with an Ea of about 80
      kcal mol-1 at temperatures below 46[deg]C and an Ea of about 27.5 kcal mol-1 at
      temperatures above 47[deg]C. The significance of these differences is discussed
      in terms of the role of protein denaturation in the thermal sensitivity of
      cucumber disc reduction of TTC and the applicability of these methods to the
      analysis of plant cellular heat sensitivity.

PMID- 12231746
TI  - Ultraviolet-Induced Photodegradation of Cucumber (Cucumis sativus L.) Microsomal
      and Soluble Protein Tryptophanyl Residues in Vitro.
AB  - The in vitro effects of ultraviolet B (280-320 nm) radiation on microsomal
      membrane proteins and partially purified ribulose bisphosphate carboxylase
      (Rubisco) from cucumber (Cucumis sativus L.) was investigated by measuring the
      direct photolytic reduction of tryptophan fluorescence and the formation of
      fluorescent photooxidation products. Exposure of microsomes and Rubisco to
      monochromatic 300-nm radiation resulted in the loss of intrinsic tryptophan
      fluorescence and the production of blue-emitting fluorophores. The major product
      of tryptophan photolysis was tentatively identified as N-formylkynurenine (N-FK).
      Even though the rates of tryptophan photodegradation and N-FK formation were
      similar, the amount of blue fluorescence produced was significantly higher in the
      microsomes relative to Rubisco. Studies with various free radical scavengers and
      other modifiers indicated that tryptophan photodegradation requires oxygen and
      that the subsequent formation of N-FK may involve reactive oxygen species. The
      optimum wavelengths for loss of typtophan fluorescence were 290 nm for the
      microsomes and 280 nm for Rubisco. The temperature dependence of tryptophan
      fluorescence and rate of tryptophan photodegradation indicated an alteration in
      the cucumber microsomal membranes at about 24[deg]C, which influenced protein
      structure and tryptophan photosensitivity.

PMID- 12231747
TI  - Freeze-Induced Membrane Ultrastructural Alterations in Rye (Secale cereale)
      Leaves.
AB  - Freezing injury in protoplasts isolated from leaves of nonaccli-mated rye (Secale
      cereale cv Puma) is associated with the formation of the inverted hexagonal (HII)
      phase. However, in protoplasts from cold-acclimated rye, injury is associated
      with the occurrence of localized deviations in the fracture plane, a lesion
      referred to as the "fracture-jump lesion." To establish that these
      ultrastructural consequences of freezing are not unique to protoplasts, we have
      examined the manifestations of freezing injury in leaves of non-acclimated and
      cold-acclimated rye by freeze-fracture electron microscopy. At -10[deg]C, injury
      in nonacclimated leaves was manifested by the appearance of aparticulate domains
      in the plasma membrane, aparticulate lamellae subtending the plasma membrane, and
      by the frequent occurrence of the HII phase. The HII phase was not observed in
      leaves of cold-acclimated rye frozen to -35[deg]C. Rather, injury was associated
      with the occurrence of the fracture-jump lesion between the plasma membrane and
      closely appressed cytoplasmic membranes. Studies of the time dependence of HII
      phase formation in nonacclimated leaves indicated that freeze-induced dehydration
      requires longer times in leaves than in isolated protoplasts. These results
      demonstrate that the freeze-induced formation of the HII phase in nonacclimated
      rye and the fracture-jump lesion in cold-acclimated rye are not unique to
      protoplasts but also occur in the leaves from which the protoplasts are isolated.

PMID- 12231748
TI  - Brassinosteroid Stimulation of Hypocotyl Elongation and Wall Relaxation in
      Pakchoi (Brassica chinensis cv Lei-Choi).
AB  - Hypocotyl elongation of pakchoi (Brassica chinensis cv Lei-Choi) was stimulated
      by applying 300 ng of brassinosteroid (2[alpha],3[alpha],22[beta],23[beta]
      tetrahydroxy-24[beta]-methyl-B-homo-7- oxa-5[alpha]-cho-le stan-6-one, BR) in 1
      [mu]L of 50% ethanol to the apex of hypocotyls. BR had its greatest effect on
      elongation of the apical 3-mm region below the cotyledonary node (75%
      stimulation) between 6 and 18 h after treatment. Stress/strain (Instron) analysis
      of this 3-mm region revealed that plastic and elastic components of extension
      were not significantly different between BR-treated and control seedlings. In
      pressure-block experiments, the initial rate of relaxation was 2-fold faster in
      BR-treated plants as compared with controls, whereas after 125 min the total
      amount of relaxation and the relaxation rate were the same for the two
      treatments. Osmotic pressure of cell sap expressed from this 3-mm region showed a
      large decrease (28%) in BR-treated seedlings compared to the controls. We
      conclude that BR stimulates growth in pakchoi by accelerating the biochemical
      processes that cause wall relaxation, without inducing a large change in wall
      mechanical properties.

PMID- 12231749
TI  - Role of Ascorbate in Detoxifying Ozone in the Apoplast of Spinach (Spinacia
      oleracea L.) Leaves.
AB  - Both reduced and oxidized ascorbate (AA and DHA) are present in the aqueous phase
      of the extracellular space, the apoplast, of spinach (Spinacia oleracea L.)
      leaves. Fumigation with 0.3 [mu]L L-1 of ozone resulted in ozone uptake by the
      leaves close to 0.9 pmol cm-2 of leaf surface area s-1. Apoplastic AA was slowly
      oxidized by ozone. The initial decrease of apoplastic AA was <0.1 pmol cm-2 s-1.
      The apoplastic ratio of AA to (AA + DHA) decreased within 6 h of fumigation from
      0.9 to 0.1. Initially, the concentration of (AA + DHA) did not change in the
      apoplast, but when fumigation was continued, DHA increased and AA remained at a
      very low constant level. After fumigation was discontinued, DHA decreased very
      slowly in the apoplast, reaching control level after 70 h. The data show that
      insufficient AA reached the apoplast from the cytosol to detoxify ozone in the
      apoplast when the ozone flux into the leaves was 0.9 pmol cm-2 s-1. The transport
      of DHA back into the cytosol was slower than AA transport into the apoplast. No
      dehydroascorbate reductase activity could be detected in the apoplast of spinach
      leaves. In contrast to its extracellular redox state, the intracellular redox
      state of AA did not change appreciably during a 24-h fumigation period. However,
      intracellular glutathi-one became slowly oxidized. At the beginning of
      fumigation, 90% of the total glutathione was reduced. Only 10% was reduced after
      24-h exposure of the leaves to 0.3 [mu]L L-1 of ozone. Necrotic leaf damage
      started to become visible when fumigation was extended beyond a 24-h period. A
      close correlation between the extent of damage, on the one hand, and the AA
      content and the ascorbate redox state of whole leaves, on the other, was observed
      after 48 h of fumigation. Only the youngest leaves that contained high ascorbate
      concentrations did not exhibit necrotic leaf damage after 48 h.

PMID- 12231750
TI  - Computer Simulation Model for the Biosynthesis of Galactosyldiacylglycerols and
      Fatty Acid Desaturation in Plants (Determination of Rates of Desaturase Activity
      in Monogalactosyldiacylglycerol).
AB  - The level of unsaturation of the constituent fatty acids of many glycerolipids in
      plant membranes is modified by environmental factors. The measurement of the rate
      of the desaturation of these fatty acids is essential to an understanding of how
      plants adapt to changing environments. This is difficult because of the
      complexity of the system and the problems involved in measuring rates of these
      enzyme reactions in cell-free preparations. A computer program has been developed
      that simulates the synthesis of galactosyldiacylglycerols and desaturation of
      their fatty acids in chloroplasts. The program uses the rate of incorporation and
      distribution of 14C in fatty acids after 14CO2 feeding to estimate rates of
      desaturation in the fatty acids of glycerolipids. Data are presented to
      demonstrate the use of the program in comparing rates of desaturation in the five
      enzyme reactions associated with monogalactosyldiacylglycerol in the
      chloroplastic pathway of leaves from Brassica napus. The method represents a
      quick, reliable, and accurate measure of desaturase activity in vivo and is the
      only method available to estimate desaturase activity of all five enzymes at the
      same time.

PMID- 12231751
TI  - Acclimation of Photosynthesis and Dark Respiration of a Submersed Angiosperm
      beneath Ice in a Temperate Lake.
AB  - Ceratophyllum demersum L. remained physiologically active beneath ice of a
      southeastern Michigan lake. The effect of seasonally low photosynthetic photon
      flux density (PPFD) and cold but nonfreezing temperature on whole-plant
      physiology was studied. Net photosynthesis was measured at six temperatures and
      12 PPFDs. Net photosynthesis, soluble protein concentration, ribulose-1,5
      bisphosphate carboxylase/oxygenase (Rubisco) protein concentration, and Rubisco
      activity of winter plants were 32, 31, 33, and 70% lower, respectively, than
      those of plants collected in the summer. Optimum temperatures for net
      photosynthesis of winter and summer plants were 5 and 30[deg]C, respectively.
      Dark respiration of winter plants was up to 313% greater than that of summer
      plants. Reduced Rubisco activity and increased dark respiration interacted to
      reduce net photosynthesis. Interaction of reduced net photosynthesis and
      increased dark respiration increased CO2 and light compensation points and the
      light saturation point of winter plants. Growth of C. demersum was limited by the
      ambient phosphorus concentration of lake water during summer. Apical stem
      segments of winter-collected plants had 54 and 35% more phosphorus and nitrogen,
      respectively, than summer-collected plants. Physiologically active perennation
      beneath ice enabled C. demersum to accumulate phosphorus during the winter when
      it was most abundant. Partial uncoupling of phosphorus acquisition from
      utilization may reduce phosphorus limitation upon growth during the summer when
      phosphorus concentration is seasonally the lowest.

PMID- 12231752
TI  - Cotranslational Integration of Soybean (Glycine max) Oil Body Membrane Protein
      Oleosin into Microsomal Membranes.
AB  - Storage triglycerides in oil seeds are sequestered in discrete organelles termed
      oil bodies. They are bounded by a monolayer of phospholipids in which a few
      distinct proteins (oleosins) are embedded. Synthesis of soybean (Glycine max) 24
      kD oleosin was analyzed by in vitro transcription and translation in reticulocyte
      lysate in the presence of canine microsomes. Our results show that 24-kD oleosin
      is cotranslationally integrated into microsomal membranes. We demonstrate that
      oleosin is integrated into a bilayer membrane in preference to the oil body
      monolayer membrane, indicating that oleosin is synthesized on the endoplasmic
      reticulum (ER). A new model of oil body assembly involving a conformational
      change through initial association with the ER membrane is proposed.

PMID- 12231753
TI  - Identification and Characterization of a Biodegradative Form of Threonine
      Dehydratase in Senescing Tomato (Lycopersicon esculentum) Leaf.
AB  - Threonine dehydratase (TD; EC.4.2.1.16) is a key enzyme involved in the
      biosynthesis of isoleucine. Inhibition of TD by isoleucine regulates the flow of
      carbon to isoleucine. We have identified two different forms of TD in tomato
      (Lycopersicon esculentum) leaves. One form, present predominantly in younger
      leaves, is inhibited by isoleucine. The other form of TD, present primarily in
      older leaves, is insensitive to inhibition by isoleucine. Expression of the
      latter enzyme increases as the leaf ages and the highest enzyme activity is
      present in the old, chlorotic leaves. The specific activity of the enzyme present
      in older leaves is much higher than the one present in younger leaves. Both forms
      can use threonine and serine as substrates. Whereas TD from the older leaves had
      the same Km (0.25 mM) for both substrates, the enzyme from the young leaves
      preferred threonine (Km = 0.25 mM) over serine (Km = 1.7 mM). The molecular
      masses of TD from the young and the old leaves were 370,000 and 200,000 D,
      respectively. High levels of the isoleucine-insensitive form of threonine
      dehydratase in the older leaves suggests an important role of threonine
      dehydratase in nitrogen remobilization in senescing leaves.

PMID- 12231754
TI  - Convexity of the Photosynthetic Light-Response Curve in Relation to Intensity and
      Direction of Light during Growth.
AB  - Photosynthesis in the intermediate light range is most efficient when the
      convexity of the photosynthetic light-response curve is high. Factors determining
      the convexity were examined for intact leaves using Salix sp. and for a plant
      cell culture using the green microalga Coccomyxa sp. It was found that the leaf
      had lower convexity than diluted plant cells because the light gradient through
      the leaf was not fully matched by a corresponding gradient in photosynthetic
      capacity. The degree to which the leaf gradients were matched was quantified by
      measuring photosynthesis at both leaf surfaces using modulated fluorescence. Two
      principal growth conditions were identified as those causing mismatch of leaf
      gradients and lowering of the convexity relative to cells. The first was growth
      under low light, where leaves did not develop any noteworthy gradient in
      photosynthetic capacity. This led to decreased convexity, particularly in old
      leaves with high chlorophyll content and, hence, steep light gradients. Second
      and less conspicuous was growth under high light conditions when light was given
      bilaterally rather than unilaterally, which yielded leaves of high photosynthetic
      capacity at both surfaces. Two situations were also identified that caused the
      convexity to decrease at the chloroplast level: (a) increased light during
      growth, for both leaves and cells, and (b) increased CO2 concentration during
      measurement of high-light-grown leaves. These changes of the intrinsic convexity
      were interpreted to indicate that the convexity declines with increased capacity
      of ribulose-1,5-bisphosphate carboxylase/oxygenase relative to the capacity of
      electron transport.

PMID- 12231755
TI  - Oleoresinosis in Grand Fir (Abies grandis) Saplings and Mature Trees (Modulation
      of this Wound Response by Light and Water Stresses).
AB  - The stem content of diterpene resin acids (rosin) increases dramatically
      following wounding of grand fir (Abies grandis) saplings, but the level of
      monoterpene olefins (turpentine) in the stem decreases following injury, in spite
      of a significant increase in monoterpene cyclase (synthase) activity. However,
      this observation was explained when rapid evaporative losses of the volatile
      monoterpenes from the wound site was demonstrated by trapping experiments, a
      finding consistent with a role of turpentine as a solvent for the mobilization
      and deposition of rosin to seal the injury. Mature forest trees responded to stem
      wounding by the enhancement of monoterpene cyclization capacity in a manner
      similar to 2-year-old grand fir saplings raised in the greenhouse. Light and
      water stresses greatly reduced the constitutive level of monoterpene cyclase
      activity and abolished the wound-induced response. The diminution in monoterpene
      biosynthetic capacity was correlated with a dramatic decrease in cyclase protein
      as demonstrated by immunoblotting. Relief of stress conditions resulted in the
      restoration of cyclase activity (both constitutive and wound induced) to control
      levels. The results of these experiments indicate that grand fir saplings are a
      suitable model for studies of the regulation of defensive oleoresinosis in
      conifers.

PMID- 12231756
TI  - Detection in Vivo of Very Rapid Red Light-Induced Calcium-Sensitive Protein
      Phosphorylation in Etiolated Wheat (Triticum aestivum) Leaf Protoplasts.
AB  - Etiolated wheat (Triticum aestivum cv Mercia) leaf protoplasts respond to brief
      red-light irradiation by increasing in volume over a 10-min incubation period
      (M.E. Bossen, H.A. Dassen, R.E. Kendrick, W.J. Vredenberg [1988] Planta 174: 94
      100). When the calcium-sensitive dye Fluo-3 was incorporated into these
      protoplasts, red-light irradiation initiated calcium transients lasting about 2
      min (P.S. Shacklock, N.D. Read, A.J. Trewavas [1992] Nature 358: 153-155).
      Release of calcium in the protoplasts by photolysis of incorporated 1-{2-amino-5
      [1-hydroxy-1-(2-nitro-4, 5-methylenedioxyphenyl)-methyl]-phenoxy}-2-(2[prime]
      amino-5[prime]-methylp henoxy)-ethane-N,N, N[prime],N[prime] -tetraccetic acid,
      tetrasodium salt (caged calcium) or caged inositol trisphosphate frequently
      induced transient increases in intracellular calcium levels, although the
      kinetics of these changes showed variation between experiments. Upon exposure to
      red light, a pronounced increase in the phosphorylation of a 70-kD and to a
      lesser extent a 60-kD peptide was observed, commencing within 15 s and continuing
      for up to 2 min. Simultaneous far-red and red irradiation attenuated the
      response. Upon release of incorporated caged calcium by cage photolysis, the
      labeling of these two peptides was greatly increased. When incorporated caged
      inositol trisphosphate was photolyzed, only the labeling of the 70-kD peptide was
      enhanced. Phosphorylation of the 70-kD peptide was also increased when
      extracellular calcium was elevated, but it decreased with increasing
      extracellular EGTA. These data thus provide direct evidence for the operation of
      an in vivo transduction sequence involving red light-dependent, calcium-sensitive
      protein phosphorylation.

PMID- 12231757
TI  - Purification and Properties of a Plasma Membrane H+-ATPase from the Extremely
      Acidophilic Alga Dunaliella acidophila.
AB  - This paper describes partial purification and characterization of a vanadate
      sensitive H+-ATPase from plasma membranes of Dunaliella acidophila, an extremely
      acidophilic unicellular alga (I. Sekler, H.U. Glaser, U. Pick [1991] J Membr Biol
      121: 51-57). Purification is based on the insolubility in and stability of the
      enzyme in Triton X-100. The purified enzyme is highly enriched in a polypeptide
      of molecular mass 100 kD, which cross-reacts with antibodies against the plant
      plasma membrane H+-ATPase. Upon reconstitution into proteoliposomes, the enzyme
      catalyzes an ATP-dependent electrogenic H+ uptake. ATP hydrolysis is stimulated
      by lipids, is inhibited by vanadate, diethylstilbestrol,
      dicyclohexylcarbodiimide, erythrosine, and mercurials, and shows a sharp optimum
      at pH 6. Unusual properties of this enzyme, by comparison with plant plasma
      membrane H+-ATPases, are a higher affinity for ATP (Km = 40 [mu]M) and a larger
      stimulation by K+, which interacts with the enzyme from its cytoplasmic side.
      Comparative studies with cross-reacting antibodies, prepared against different
      domains of the plant H+-ATPase, suggest that the central hydrophilic domain
      containing the catalytic site is more conserved than the C- and N-terminal ends.
      The high abundance and stability of the plasma membrane H+-ATPase from D.
      acidophila make it an attractive model system for studies of the structure
      function relations and regulation of this crucial enzyme.

PMID- 12231758
TI  - Growth Depression in Mycorrhizal Citrus at High-Phosphorus Supply (Analysis of
      Carbon Costs).
AB  - Mycorrhizal-induced growth depression of plants in high-P soil has been reported
      in many species. The carbon costs of factors contributing to this growth
      depression were analyzed in Volkamer lemon (Citrus volkameriana Tan. & Pasq.)
      colonized by the mycorrhizal (M) fungus Glomus intraradices Schenck and Smith. M
      and nonmycorrhizal (NM) plants were each grown at two P-supply rates. Carbon
      budgets of M and NM plants were determined by measuring whole-plant carbon
      assimilation and respiration rates using gas-exchange techniques. Biomass, M
      colonization, tissue-P concentration, and total fatty acid concentration in the
      fibrous roots were determined. Construction costs of the fibrous roots were
      estimated from heat of combustion, N, and ash content. Root-growth respiration
      was derived from daily root growth and root-construction cost. M and NM plants
      grown in high-P soil were similar in P concentration, daily shoot carbon
      assimilation, and daily shoot dark respiration. At 52 d after transplanting
      (DAT), however, combined daily root plus soil respiration was 37% higher for M
      than for NM plants, resulting in a 20% higher daily specific carbon gain (mmol
      CO2 [mmol carbon]-1 d-1) in NM than M plants. Estimates of specific carbon gain
      from specific growth rates indicated about a 10% difference between M and NM
      plants. Absolute values of specific carbon gain estimated by whole-plant gas
      exchange and by growth analysis were in general agreement. At 52 DAT, M and NM
      plants at high P had nearly identical whole-plant growth rates, but M plants had
      19% higher root dry weight with 10% higher daily rates of root growth. These
      allocation differences at high P accounted for about 51% of the differences in
      root/soil respiration between M and NM plants. Significantly higher fatty acid
      concentrations in M than NM fibrous roots were correlated with differences in
      construction costs of the fibrous roots. Of the 37% difference in daily total
      root/soil respiration observed between high-P M and NM plants at 52 DAT,
      estimated daily growth respiration accounted for only about 16%, two-thirds of
      which was associated with construction of lipid-rich roots, and the remaining one
      third with greater M root growth rates. Thus, of the 37% more root/soil
      respiration associated with M colonization of high-P plants, 10% was directly
      attributable to building lipid-rich roots, 51% to greater M root biomass
      allocation, and the remaining 39% could have been used for maintenance of the
      fungal tissue in the root and growth and maintenance of the extramatrical hyphae.

PMID- 12231759
TI  - Pyrophosphorylases in Solanum tuberosum (IV. Purification, Tissue Localization,
      and Physicochemical Properties of UDP-Glucose Pyrophosphorylase).
AB  - The enzyme UDP-glucose pyrophosphorylase (UGPase) from potato (Solanum tuberosum
      L. cv Norchip) tubers was purified 177-fold to near homogeneity and to a specific
      activity of 1099 international units/mg of protein. The molecular mass of the
      purified enzyme was 53 kD as determined by SDS-PAGE and gel filtration.
      Immunological and activity assays detected UGPase at similar levels in potato
      stems, stolons, and tubers. Leaves and roots contained lower levels of UGPase
      activity and protein. Lineweaver-Burk plots for substrates inorganic
      pyrophosphate and UDP-glucose were linear in the pyrophosphorolytic direction,
      yielding Km values of 0.13 and 0.14 mM, respectively. However, Lineweaver-Burk
      plots for the substrates glucose-1-P and UTP were biphasic in nature when UGPase
      was assayed in the direction of UDP-glucose synthesis. At physiological substrate
      concentrations (i.e. from 0.05-0.20 mM), Km values of 0.08 mM (glucose-1-P) and
      0.12mM (UTP) were obtained. When substrate concentrations increased above 0.20
      mM, Km values increased to 0.68 mM (glucose-1-P) and 0.53 mM (UTP). These kinetic
      patterns of potato UGPase suggest a "negative cooperative effect" (A. Conway,
      D.E. Koshland, Jr. [1968] Biochemistry 7: 4011-4022) with respect to the
      substrates glucose-1-P and UTP. The biphasic substrate saturation curves were
      similar to the kinetics of the dimeric form of UGPase purified from Salmonella
      typhimurium (T. Nakae [1971] J Biol Chem 246: 4404-4411). The in vivo
      significance of the enzyme's "negative cooperativity" in the direction of UDP
      glucose synthesis and potato sweetening is discussed.

PMID- 12231760
TI  - Sensitivity to an Ethylene Biosynthesis-Inducing Endoxylanase in Nicotiana
      tabacum L. cv Xanthi Is Controlled by a Single Dominant Gene.
AB  - The ethylene biosynthesis-inducing xylanase (EIX) is known to be a potent
      elicitor of ethylene biosynthesis and other responses when applied to leaf tissue
      of Nicotiana tabacum L. cv Xanthi. In contrast, leaf tissue of the tobacco
      cultivar Hicks was insensitive to EIX at concentrations 100-fold higher than was
      needed to elicit responses from Xanthi. Cell-suspension cultures of Xanthi and
      Hicks showed similar differences in sensitivity to EIX. Equivalent levels of
      ethylene production were elicited in leaf discs of both cultivars after treatment
      with CuSO4. The F1 and Xanthi backcross progeny of Hicks and Xanthi crosses were
      all sensitive to EIX, whereas the F2 and Hicks backcross progeny segregated for
      sensitivity to EIX. Individual plants from the F2 and Hicks backcross that were
      insensitive to EIX produced only insensitive progeny when they were self
      pollinated. Progeny from sensitive plants either segregated for sensitivity to
      EIX or produced all sensitive progeny (an F2 plant). Sensitivity to EIX is
      controlled by a single dominant gene, based on chi-square analysis of segregation
      ratios.

PMID- 12231761
TI  - Expression of the Acc1 Gene-Encoded Acetyl-Coenzyme A Carboxylase in Developing
      Maize (Zea mays L.) Kernels.
AB  - A mutation (Acc1-S2) in the structural gene for maize (Zea mays L.) acetyl
      coenzyme A carboxylase (ACCase) that significantly reduces sethoxydim inhibition
      of leaf ACCase activity was used to investigate the gene-enzyme relationship
      regulating ACCase activity during oil deposition in developing kernels. Mutant
      embryo and endosperm ACCase activities were more than 600-fold less sensitive to
      sethoxydim inhibition than ACCase in wild-type kernel tissues. Moreover, in vitro
      cultured mutant kernels developed normally in the presence of sethoxydim
      concentrations that inhibited wild-type kernel development. The results indicate
      that the Acc1-encoded ACCase accounts for the majority of ACCase activity in
      developing maize kernels, suggesting that Acc1-encoded ACCase functions not only
      during membrane biogenesis in leaves but is also the predominant form of ACCase
      involved in storage lipid biosynthesis in maize embryos.

PMID- 12231762
TI  - Electrotropism of Maize (Zea mays L.) Roots (Facts and Artifacts).
AB  - Intact and decapped primary roots of maize (Zea mays L.) were exposed to DC
      electric fields of 0.5 to 8.0 V/cm in low-salinity media to resolve conflicting
      results about the direction of electrotropism. In DC fields of 0.5 V/cm or 1.0
      V/cm, intact roots always curved toward the cathode. In a field of 8.0 V/cm,
      intact roots curved toward the anode and stopped growth. Decapped roots also
      curved toward the anode both in weak and strong fields. The results indicate that
      growth toward the cathode is the true response of healthy roots.

PMID- 12231763
TI  - Structural Cell Wall Proteins.

PMID- 12231764
TI  - [beta]-Glucan Synthesis in the Cotton Fiber (I. Identification of [beta]-1,4- and
      [beta]-1,3-Glucans Synthesized in Vitro).
AB  - In vitro [beta]-glucan products were synthesized by digitonin-solubilized enzyme
      preparations from plasma membrane-enriched fractions of cotton (Gossypium
      hirsutum) fiber cells. The reaction mixture favoring [beta]-1,4-glucan synthesis
      included the following effectors: Mg2+, Ca2+, cellobiose, cyclic
      3[prime]:5[prime]-GMP, and digitonin. The ethanol insoluble fraction from this
      reaction contained [beta]-1,4-glucan and [beta]-1,3-glucan in an approximate
      ratio of 25:69. Approximately 16% of the [beta]-1,4-glucan was resistant to the
      acetic/nitric acid reagent. The x-ray diffraction pattern of the treated product
      favoring [beta]-1,4-glucan synthesis strongly resembled that of cellulose II. On
      the basis of methylation analysis, the acetic/nitric acid reagent-insoluble
      glucan product was found to be exclusively [beta]-1,4-linked. Enzymic hydrolysis
      confirmed that the product was hydrolyzed only by cellobiohydrolase I.
      Autoradiography proved that the product was synthesized in vitro. The degree of
      polymerization (DP) of the in vitro product was estimated by nitration and size
      exclusion chromatography; there were two average DPs of 59 (70%) and 396 (30%)
      for the [beta]-1,3-glucanase-treated sample, and an average DP of 141 for the
      acetic/nitric acid reagent-insoluble product. On the basis of product analysis,
      the positive identification of in vitro-synthesized cellulose was established.

PMID- 12231765
TI  - [beta]-Glucan Synthesis in the Cotton Fiber (II. Regulation and Kinetic
      Properties of [beta]-Glucan Synthases.
AB  - The regulation and kinetic properties of cellulose synthase as well as [beta]-1,3
      glucan synthase have been studied. The cellulose was detected using acetic/nitric
      acid insolubility as an indicator of cellulose (this product contained only
      [beta]-1,4-linked glucans; K. Okuda, L. Li, K. Kudlicka, S. Kuga, R.M. Brown, Jr.
      [1993] Plant Physiol 101: 1131-1142). These studies reveal that (a) [beta]-1,3
      glucan synthesis is enhanced up to 31-fold by cellobiose with a Ka of 1.16 mM;
      (b) cellulose synthesis is increased 12-fold by a combination of cellobiose (Ka =
      3.26 mM) and cyclic-3[prime]:5[prime]-GMP (Ka = 100 [mu]M); (c) the common
      components in the reaction mixture required by both enzymes are cellobiose,
      calcium, and digitonin; (d) cellulose synthase has an essential requirement for
      magnesium (Ka = 0.89 mM); (e) cellulose synthase also requires a low
      concentration of calcium (Ka = 90 [mu]M); (f) the optimal pH for cellulose
      synthase (7.6-8.0) is slightly higher than that for [beta]-1,3-glucan synthase
      (7.2-7.6); (g) the Km for UGP-Glc for cotton (Gossypium hirsutum) cellulose
      synthase is 0.40 mM; (h) the Km for UDP-Glc for for [beta]-1,3-glucan synthase is
      0.43 mM.

PMID- 12231766
TI  - [beta]-Glucan Synthesis in the Cotton Fiber (III. Identification of UDP-Glucose
      Binding Subunits of [beta]-Glucan Synthases by Photoaffinity Labeling with
      [[beta]-32P]5[prime]-N3-UDP-Glucose.
AB  - Using differential product entrapment and photolabeling under specifying
      conditions, we identifIed a 37-kD polypeptide as the best candidate among the UDP
      glucose-binding polypeptides for the catalytic subunit of cotton (Gossypium
      hirsutum) cellulose synthase. This polypeptide is enriched by entrapment under
      conditions favoring [beta]-1,4-glucan synthesis, and it is magnesium dependent
      and sensitive to unlabeled UDP-glucose. A 52-kD polypeptide was identified as the
      most likely candidate for the catalytic subunit of [beta]-1,3-glucan synthase
      because this polypeptide is the most abundant protein in the entrapment fraction
      obtained under conditions favoring [beta]-1,3-glucan synthesis, is coincident
      with [beta]-1,3-glucan synthase activity, and is calcium dependent. The possible
      involvement of other polypeptides in the synthesis of [beta]-1,3-glucan is
      discussed.

PMID- 12231767
TI  - Is Acetylcarnitine a Substrate for Fatty Acid Synthesis in Plants?
AB  - Long-chain fatty acid synthesis from [1-14C]acetylcarnitine by chloroplasts
      isolated from spinach (Spinacia oleracea), pea (Pisum sativum), amaranthus
      (Amaranthus lividus), or maize (Zea mays) occurred at less than 2% of the rate of
      fatty acid synthesis from [1-14C]acetate irrespective of the maturity of the
      leaves or whether the plastids were purified using sucrose or Percoll medium. [1
      14C]-Acetylcarnitine was not significantly utilized by highly active chloroplasts
      rapidly prepared from pea and spinach using methods not involving density
      gradient centrifugation. [1-14C]Acetylcarnitine was recovered quantitatively from
      chloroplast incubations following 10 min in the light. Unlabeled acetyl-L
      carnitine (0.4 mM) did not compete with [1-14C]acetate (0.2 mM) as a substrate
      for fatty acid synthesis by any of the more than 70 chloroplast preparations
      tested in this study. Carnitine acetyltransferase activity was not detected in
      any chloroplast preparation and was present in whole leaf homogenates at about
      0.1% of the level of acetyl-coenzyme A synthetase activity. When supplied to
      detached pea shoots and detached spinach, amaranthus, and maize leaves via the
      transpiration stream, 1 to 4% of the [1-14C]acetylcarnitine and 47 to 57% of the
      [1-14C]acetate taken up was incorporated into lipids. Most (78-82%) of the [1
      14C]acetylcarnitine taken up was recovered intact. It is concluded that
      acetylcarnitine is not a major precursor for fatty acid synthesis in plants.

PMID- 12231768
TI  - Long-Term Anaerobic Metabolism in Root Tissue (Metabolic Products of Pyruvate
      Metabolism).
AB  - The onset of anaerobiosis in barley root tissue (Hordeum vulgare L. cv Himalaya)
      results in the following metabolic responses. There are rapid increases in the
      levels of pyruvate, lactate, and ethanol. Malate and succinate concentrations
      increase over the first 12 h, after which they return to the levels found in
      oxygenated root tissue. Alanine concentration increases over the first 12 h, and
      this is matched by a corresponding decrease in aspartate. The initial
      stoichiometric decline in aspartate and increase in alanine suggests that the
      amino group of aspartate is conserved by transaminating pyruvate to alanine.
      Aspartate catabolism also probably provides the initial source of carbon for
      reduction to succinate under anoxic conditions. Under long-term anaerobiosis (>24
      h), there is no further accumulation of any of the fermentative end products
      other than ethanol, which also represents the major metabolic end product during
      long-term anaerobiosis. Although a number of the enzymes involved in fermentative
      respiration have been found to be induced under anaerobic conditions, neither
      aspartate amino-transferase nor malate dehydrogenase is induced in barley root
      tissue. The observations suggest that the long-term adaptations to hypoxic
      conditions may be quite different than the more well-characterized short-term
      adaptations.

PMID- 12231769
TI  - Effects of Anaerobiosis on Chlorophyll Fluorescence Yield in Spinach (Spinacia
      oleracea) Leaf Discs.
AB  - When spinach (Spinacia oleracea) leaf discs were incubated in a dark anaerobic
      environment, the chlorophyll fluorescence yield was much increased relative to
      the aerobic control. Occasionally, the fluorescence yield of the darkened
      anaerobic samples approached 80% of the maximum fluorescence. The anaerobic
      incubation period also induced in a leaf disc the capacity to exhibit a low light
      mediated chlorophyll fluorescence induction phenomenon. This involved a rapid and
      slow increase in fluorescence yield, followed by a slow quenching. This could be
      induced by light levels as low as 400 [mu]W m-2. The anaerobic-dependent increase
      in chlorophyll fluorescence yield could be relaxed by either far-red light, O2,
      or a saturating pulse of white light. It was concluded that the anaerobic
      dependent increase in chlorophyll fluorescence yield was due to a dark reduction
      of the plastoquinone pool and its relaxation by reoxidation. Darkened isolated
      chloroplasts did not exhibit a fluorescence yield increase under anaerobic
      conditions. Fluorescence slowly increased only when dithiothreitol or dithionite
      was added.

PMID- 12231771
TI  - Porphyrin Accumulation and Export by Isolated Barley (Hordeum vulgare) Plastids
      (Effect of Diphenyl Ether Herbicides).
AB  - We have investigated the formation of porphyrin intermediates by isolated barley
      (Hordeum vulgare) plastids incubated for 40 min with the porphyrin precursor 5
      aminolevulinate and in the presence and absence of a diphenylether herbicide that
      blocks protoporphyrinogen oxidase, the enzyme in chlorophyll and heme synthesis
      that oxidizes protoporphyrinogen IX to protoporphyrin IX. In the absence of
      herbicide, about 50% of the protoporphyrin IX formed was found in the
      extraplastidic medium, which was separated from intact plastids by centrifugation
      at the end of the incubation period. In contrast, uroporphyrinogen, an earlier
      intermediate, and magnesium protoporphyrin IX, a later intermediate, were located
      mainly within the plastid. When the incubation was carried out in the presence of
      a herbicide that inhibits protoporphyrinogen oxidase, protoporphyrin IX formation
      by the plastids was completely abolished, but large amounts of protoporphyrinogen
      accumulated in the extraplastidic medium. To detect extraplastidic
      protoporphyrinogen, it was necessary to first oxidize it to protoporphyrin IX
      with the use of a herbicide-resistant protoporphyrinogen oxidase enzyme present
      in Escherichia coli membranes. Protoporphyrinogen is not detected by some
      commonly used methods for porphyrin analysis unless it is first oxidized to
      protoporphyrin IX. Protoporphyrin IX and protoporphyrinogen found outside the
      plastid did not arise from plastid lysis, because the percentage of plastid
      lysis, measured with a stromal marker enzyme, was far less than the percentage of
      these porphyrins in the extraplastidic fraction. These findings suggest that of
      the tetrapyrrolic intermediates synthesized by the plastids, protoporphyrinogen
      and protoporphyrin IX, are the most likely to be exported from the plastid to the
      cytoplasm. These results help explain the extraplastidic accumulation of
      protoporphyrin IX in plants treated with photobleaching herbicides. In addition,
      these findings suggest that plastids may export protoporphyrinogen or
      protoporphyrin IX for mitochondrial heme synthesis.

PMID- 12231772
TI  - Thermal Instability of Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase from a
      Temperature-Conditional Chloroplast Mutant of Chlamydomonas reinhardtii.
AB  - Mutant 68-4PP of Chlamydomonas reinhardtii has only 10% of the normal level of
      ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) holoenzyme when grown
      at 35[deg]C. However, when grown at 25[deg]C, the amount of holoenzyme is greater
      than 35% of the wild-type level, and the purified enzyme has a reduced CO2/O2
      specificity factor. These mutant characteristics result from a chloroplast
      mutation that causes leucine-290 to be replaced by phenylalanine within the
      Rubisco large-subunit protein. A nuclear mutation (named S52-2B) was previously
      identified that can suppress both the in vivo instability and reduced CO2/O2
      specificity of the mutant enzyme. However, the effect of this nuclear mutation on
      the in vitro stability of the holoenzyme was not resolved. In the present study,
      purified Rubisco from mutant 68-4PP was found to be less thermally stable than
      the wild-type enzyme, and it had maximal carboxylase activity at a lower
      temperature. When incubated at 35[deg]C, the mutant enzyme lost carboxylase
      activity at a much faster rate than the wild-type enzyme. However, the nuclear
      S52-2B suppresor mutation improved the thermal stability of the mutant enzyme in
      all cases. These results indicate that structural changes in mutant 68-4PP
      Rubisco can account for its observed inactivation in vitro and degradation in
      vivo. Such structural alterations are alleviated by the function of a nuclear
      gene.

PMID- 12231773
TI  - The Low CO2-Inducible 36-Kilodalton Protein Is Localized to the Chloroplast
      Envelope of Chlamydomonas reinhardtii.
AB  - The localization of the 36-kD polypeptide of Chlamydomonas reinhardtii induced by
      photoautotrophic growth on low CO2 concentrations (0.03% in air [v/v], low CO2
      grown cells) has been investigated. This polypeptide was specifically localized
      to the chloroplast envelope membranes isolated from low CO2-grown cells and was
      not present in the chloroplast envelopes isolated from high (5% CO2 in air [v/v])
      CO2-grown cells. The 36-kD protein does not show carbonic anhydrase activity and
      was not present on the plasma membranes isolated from low CO2-grown cells. This
      protein may, in part, account for the different inorganic carbon uptake
      characteristics observed in chloroplasts isolated from high and low CO2-grown
      cells of C. reinhardtii.

PMID- 12231774
TI  - Phosphate Translocator of Isolated Guard-Cell Chloroplasts from Pisum sativum L.
      Transports Glucose-6-Phosphate.
AB  - Chloroplasts were isolated from ruptured guard-cell protoplasts of the Argenteum
      mutant of Pisum sativum L. and purified by centrifugation through a Percoll
      layer. The combined volume of the intact plastids and the uptake of phosphate
      were determined by silicone oil-filtering centrifugation, using tritiated water
      and [14C]sorbitol as membrane-permeating and nonpermeating markers and
      [32P]phosphate as tracer for phosphate. The affinities of the phosphate
      translocator for organic phosphates were assessed by competition with inorganic
      phosphate. The affinities for dihydroxyacetone phosphate, 3-phosphoglycerate
      (PGA), and phosphoenolpyruvate were in the same order as those reported for
      mesophyll chloroplasts of several species. However, the guard-cell phosphate
      translocator had an affinity for glucose-6-phosphate that was as high as that for
      PGA. Guard-cell chloroplasts share this property with amyloplasts from the root
      of pea (H.W. Heldt, U.I. Flugge, S. Borchert [1991] Plant Physiol 95: 341-343).
      An ability to import glucose-6-phosphate enables guard-cell chloroplasts to
      synthesize starch despite the reported absence of a fructose-1,6-bisphosphatase
      activity in the plastids, which would be required if only C3 phosphates could
      enter through the translocator.

PMID- 12231775
TI  - Expression of Low Molecular Weight Heat-Shock Proteins under Field Conditions.
AB  - Heat-shock proteins (HSPs) are known to be expressed in plants experiencing high
      temperature stress. We have examined the expression of class I cytoplasmic low
      molecular weight (LMW) HSPs and find that these HSPs also frequently accumulate
      in seeds, seed pods, and flowers during a normal growing season. We first
      examined the expression of class I cytoplasmic LMW HSPs by western blot analysis
      in a range of seed samples from both commercially grown and wild legumes. LMW
      HSPs were present in all seed samples, indicating that these HSPs are regularly
      expressed in these tissues. To examine more specifically conditions under which
      LMW HSPs were produced during an average growing season, additional studies of
      Medicago sativa were carried out during the fall season in Tucson, AZ. Plants
      were irrigated to avoid conditions of water stress, and canopy temperature was
      monitored throughout the study period. LMW HSP expression in leaves, flowers, and
      developing seed pods was analyzed by western blotting. Results show that in the
      field HSPs are frequently produced in flowers and seed pods, even in plants that
      show no HSP expression in leaves. Parallel greenhouse studies indicate that HSP
      expression in seeds is in part developmentally regulated. In total our data
      suggest a more widespread occurrence of HSPs in optimal growth environments and
      emphasize their potential role during reproduction.

PMID- 12231776
TI  - Elevated Levels of Both Sucrose-Phosphate Synthase and Sucrose Synthase in Vicia
      Guard Cells Indicate Cell-Specific Carbohydrate Interconversions.
AB  - A long series of reports correlate larger stomatal aperture size with elevated
      concentration of sucrose (Suc) in guard cells. To assess the role and autonomy of
      guard cells with respect to these changes, we have determined quantitatively the
      cellular distribution of the synthetic enzyme, Suc-phosphate synthase (SPS) and
      the degradative enzyme Suc synthase (SS) in Vicia leaflet. As expected for Suc
      exporting cells, the photosynthetic parenchyma had a high SPS:SS ratio of
      approximately 45. Also as expected, in epidermal cells, which had only few and
      rudimentary plastids, the SPS:SS ratio was low (0.4). Of all cells and tissues
      measured, those that had the highest specific activity of SPS (about 4.8 [mu]mol
      mg-1 of protein h-1) were guard cells. Guard cells also had a very high relative
      specific activity of SS.

PMID- 12231777
TI  - Maintenance of Chloroplast Components during Chromoplast Differentiation in the
      Tomato Mutant Green Flesh.
AB  - During ripening of tomato (Lycopersicon esculentum) fruit, chloroplasts develop
      into chromoplasts. The chloroplast-chromoplast transition is marked by the
      accumulation of carotenoids and the disappearance of chlorophyll, the degradation
      of the highly structured thylakoid membrane system, and a reduction in the levels
      of proteins and mRNAs associated with photosynthesis. In the tomato mutant green
      flesh (gf), detectable amounts of chlorophyll remain in the ripe, mutant fruit,
      giving rise to a rusty red fruit color and suggesting that at least chlorophyll
      degradation is defective in the mutant. We show here that the ultrastructure of
      the plastids in the ripe gf fruit maintained significant amouonts of the
      chloroplast thylakoid grana along with structures characteristic of tomato
      chromoplasts. The maintenance of chloroplast structure in the gf ripe fruit was
      paralleled on the molecular level by the retention of plastid photosynthetic
      components that normally decline significantly in ripening tomato fruits. These
      included the light-harvesting chlorophyll a/b-binding proteins of photosystem II,
      the second electron accepting plastoquinone of photosystem II binding protein,
      the large and small subunits of ribulose bisphosphate carboxylase/oxygenase, the
      33-kD oxygen evolution protein, and cytochrome b559. Similarly, photosynthetic
      transcripts, cab, psbA, rbcL, rbcS, and psbE mRNAs, also accumulated to higher
      levels in ripening gf fruit than wild type. It is interesting that the levels of
      some of these transcripts, especially cab mRNA, were noticeably higher in the
      mature gf green fruit than in the corresponding wild-type fruit. This suggests
      that the onset of the effect from the gf mutation might be earlier than fruit
      ripening. We also observed that when chloroplast formation was blocked during the
      development and ripening of gf fruit, these mutant fruits were bright red and
      their chromoplasts were indistinguishable from those found in wild-type ripe
      fruits grown and ripened either in the dark or in the light. These results
      suggest that the lesion in gf may alleviate conditions associated with
      chloroplast deterioration during the chloroplast-chromoplast transition in tomato
      ripening but has no direct effect on chromoplast differentiation per se. The
      ultrastructure of gf provides unequivocal evidence that, in ripening tomato,
      chromoplasts indeed differentiate from preexisting chloroplasts; on the other
      hand, chromoplast differentiation in the dark-matured and -ripened tomato fruits
      indicates that chromoplast development can be a process entirely independent of
      the chloroplasts.

PMID- 12231778
TI  - Induction and Characterization of a Cytochrome P-450-Dependent Camphor
      Hydroxylase in Tissue Cultures of Common Sage (Salvia officinalis).
AB  - (+)-Camphor, a major monoterpene of the essential oil of common sage (Salvia
      officinalis), is catabolized in senescent tissue, and the pathway for the
      breakdown of this bicyclic ketone has been previously elucidated in sage cell
      suspension cultures. In the initial step of catabolism, camphor is oxidized to 6
      exo-hydroxycamphor, and the corresponding NADPH- and O2-dependent hydroxylase
      activity was demonstrated in microsomal preparations of sage cells. Several well
      established inhibitors of cytochrome P-450-dependent reactions, including
      cytochrome c, clotrimazole, and CO, inhibited the hydroxylation of camphor, and
      CO-dependent inhibition was partially reversed by blue light. Upon treatment of
      sage suspension cultures with 30 mM MnCl2, camphor-6-hydroxylase activity was
      induced up to 7-fold. A polypeptide with estimated molecular mass of 58 kD from
      sage microsomal membranes exhibited antigenic cross-reactivity in western blot
      experiments with two heterologous polyclonal antibodies raised against cytochrome
      P-450 camphor-5-exo-hydroxylase from Pseudomonas putida and cytochrome P-450
      limonene-6S-hydroxylase from spearmint (Mentha spicata). Dot blotting indicated
      that the concentration of this polypeptide increased with camphor hydroxylase
      activity in microsomes of Mn2+-induced sage cells. These results suggest that
      camphor-6-exo-hydroxylase from sage is a microsomal cytochrome P-450
      monooxygenase that may share common properties and epitopes with bacterial and
      other plant monoterpene hydroxylases.

PMID- 12231779
TI  - Glutamine Synthetase and Ferredoxin-Dependent Glutamate Synthase Expression in
      the Maize (Zea mays) Root Primary Response to Nitrate (Evidence for an Organ
      Specific Response).
AB  - To define further the early, or primary, events that occur in maize (Zea mays)
      seedlings exposed to NO3-, accumulation of chloroplast glutamine synthetase (GS2;
      EC 6.3.1.2) and ferredoxin-dependent glutamate synthase (Fd-GOGAT; EC 1.4.7.1),
      transcripts were examined in roots and leaves. In roots, NO3- treatment caused a
      rapid (within 30 min), transient, and cycloheximide-independent accumulation of
      GS2 and Fd-GOGAT transcripts. In addition, 10 [mu]M external NO3- was sufficient
      to cause transcript accumulation. The induction was NO3- specific, since NH4Cl
      treatment did not affect mRNA levels. GS2 and Fd-GOGAT mRNA accumulation in roots
      was similar to that observed for nitrate reductase (NR) mRNA. Therefore, the four
      genes involved in NO3- assimilation (NR, nitrite reductase, GS2, and Fd-GOGAT)
      are expressed in the root primary response to NO3-, suggesting that all four
      genes can respond to the same signal transduction system. In contrast, relatively
      high levels of GS2 and Fd-GOGAT mRNAs were present in untreated leaf tissue, and
      NO3- treatment had little or no influence on transcript accumulation. Rapid,
      transient, and cycloheximide-independent NR mRNA expression was seen in the NO3-
      treated leaves, demonstrating that NO3- was not limiting. The NO3--independent
      constitutive expression of GS2 and Fd-GOGAT is likely due to the requirement for
      reassimilation of photorespiratory NH4+ in these young leaves.

PMID- 12231780
TI  - Changes in the Content of Two Glutamate Synthase Proteins in Spikelets of Rice
      (Oryza sativa) Plants during Ripening.
AB  - Nitrogen accumulation in the apical spikelets on the primary branches of the main
      stem of rice plants have been studied during the ripening process (0-35 d after
      flowering). The level of NADH-dependent glutamate synthase (GOGAT) protein and
      activity increased 4- and 6-fold, respectively, in the first 15 d after
      flowering. Maximum levels of NADH-GOGAT were found at that time when the
      spikelets had just begun to increase in dry weight and to accumulate storage
      proteins. Subsequently, both the level of NADH-GOGAT protein and its activity in
      spikelets declined rapidly. Although changes in ferredoxin (Fd)-dependent GOGAT
      paralleled changes in NADH-GOGAT, the relative abundance of NADH-GOGAT protein in
      the spikelets was about 3 times higher than that of Fd-GOGAT from 5 to 15 d after
      flowering. When the chaff (lemma and palea) was separated from the spikelets 10 d
      after the flowering, 16% of the NADH-GOGAT protein was found in the chaff and 84%
      in the young grain tissues (endosperm, testae, aleurone tissues, and embryo). On
      the other hand, Fd-GOGAT protein was distributed 52% in the chaff and 48% in the
      young grain tissues in spikelets of the same age. Activity of NADP-isocitrate
      dehydrogenase, which may generate the 2-oxoglutarate required for the GOGAT
      reactions, was much higher than that of total GOGAT activities on a spikelet
      basis during the ripening process. These results suggest that in rice plants NADH
      GOGAT is responsible for the synthesis of glutamate from the glutamine that is
      transported from senescing tissues to the spikelets.

PMID- 12231781
TI  - The Effects of Aluminum on the Influx of Calcium, Potassium, Ammonium, Nitrate,
      and Phosphate in an Aluminum-Sensitive Cultivar of Barley (Hordeum vulgare L.).
AB  - The mechanism by which aluminum interferes with ion influx is not known. In this
      study, the effects of aluminum on the influx of the cations calcium, potassium,
      and ammonium and the anions nitrate and phosphate were measured in an aluminum
      sensitive cultivar of barley (Hordeum vulgare L.). Aluminum (100 [mu]M) was found
      to inhibit the influx of the cations calcium (69%), ammonium (40%), and potassium
      (13%) and enhancing the influx of the anions nitrate (44%) and phosphate (17%).
      Aluminum interfered with the binding of the cations in the cell wall by the same
      order of magnitude as their respective influxes, whereas phosphate binding was
      strongly enhanced. The results are consistent with a mechanism whereby aluminum
      binds to the plasma membrane phospholipids, forming a positively charged layer
      that influences ion movement to the binding sites of the transport proteins. A
      positive charge layer would retard the movement of cations and increase the
      movement of anions to the plasma membrane in proportion to the charges carried by
      these ions.

PMID- 12231782
TI  - Phosphorylation of Soybean (Glycine max L.) Nodule Phosphoenolpyruvate
      Carboxylase in Vitro Decreases Sensitivity to Inhibition by L-Malate.
AB  - Phosphoenolpyruvate carboxylase (PEPC) from soybean (Glycine max L.Merr.) nodules
      was purified 187-fold to a final specific activity of 56 units mg-1 of protein.
      Sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) revealed
      one major polypeptide band, with a molecular mass of 110 kD, after the final
      purification step. Two-dimensional PAGE resolved four isoelectric forms of the
      purified enzyme. Antibodies raised against the purified enzyme immunoprecipitated
      PEPC activity from a desalted nodule extract. Two cross-reacting bands were
      obtained when protein immunoblots of crude nodule extracts subjected to SDS-PAGE
      were probed with the antiserum. One of these corresponded to the 110-kD subunit
      of PEPC, and the other had a molecular mass of about 60 kD. PEPC was shown to be
      activated in a time-dependent manner when desalted soybean nodule extracts were
      preincubated with Mg.ATP in vitro. Activation was observed when PEPC was assayed
      at pH 7 in the absence of glycerol but not at pH 8 in the presence of glycerol.
      When o.5 mM L-malate was included in the assay, activation was much more
      pronounced than without malate. Maximal activation was 30% in the absence of L
      malate and 200% in its presence. The L-malate concentrations producing 50%
      inhibition of PEPC activity were o.35 and 1.24 mM, respectively, before and after
      preincubation with Mg.ATP. The antiserum against soybean nodule PEPC was used to
      immunoprecipitate PEPC from a desalted nodule extract that had been preincubated
      with Mg.[[gamma]-32P]ATP. The immunoprecipitate was then subjected to SDS-PAGE,
      followed by autoradiography. The autoradiograph revealed intense labeling of the
      110-kD subunit of PEPC following preincubation with [[gamma]-32P]ATP. The data
      suggest that soybean nodule PEPC becomes phosphorylated by an endogenous protein
      kinase, resulting in decreased sensitivity of the enzyme to inhibition by L
      malate in vitro. The results are discussed in relation to the proposed functions
      of PEPC in legume nodules.

PMID- 12231783
TI  - Differential Expression of Two Soybean (Glycine max L.) Proline-Rich Protein
      Genes after Wounding.
AB  - We have investigated the wound-induced expression of two members of the soybean
      (Glycine max L.) proline-rich cell wall protein gene family and show that SbPRP1
      and SbPRP2 exhibit unique patterns of expression after physical damage. SbPRP1
      mRNA can be detected in the hook of soybean seedlings within 2 h after wounding
      and is present at high levels in the hook and elongating hypocotyl 20 h after
      wounding. In contrast, SbPRP2 mRNA increases transiently and rapidly throughout
      the soybean seedling after wounding. SbPRP2 is also induced by wounding in
      soybean leaves, but the pattern of mRNA accumulation in leaves is distinct from
      that seen in seedlings and reaches high levels of expression 20 h after physical
      damage. SbPRP2 mRNA levels were also found to increase in the mature hypocotyl
      and roots of seedlings in response to treatment with 10 [mu]M indoleacetic acid
      and naphthalene-1-acetic acid. These data indicate that the wound-induced
      expression of PRPs in soybean is tissue specific and that the regulation of these
      genes after physical damage may operate through different signal transduction
      pathways.

PMID- 12231784
TI  - Photoregulation of Fructose and Glucose Respiration in the Intact Chloroplasts of
      Chlamydomonas reinhardtii F-60 and Spinach.
AB  - The photoregulation of chloroplastic respiration was studied by monitoring in
      darkness and in light the release of 14CO2 from whole chloroplasts of
      Chlamydomonas reinhardtii F-60 and spinach (Spinacia oleracea L.) supplied
      externally with [14C] glucose and [14C]-fructose, respectively. CO2 release was
      inhibited more than 90% in both chloroplasts by a light intensity of 4 W m-2.
      Oxidants, oxaloacetate in Chlamydomonas, nitrite in spinach, and phenazine
      methosulfate in both chloroplasts, reversed the inhibition. The onset of the
      photoinhibitory effect on CO2 release was relatively rapid compared to the
      restoration of CO2 release following illumination. In both darkened chloroplasts,
      dithiothreitol inhibited release. Of the four enzymes (fructokinase,
      phosphoglucose isomerase, glucose-6-P dehydrogenase, and gluconate-6-P
      dehydrogenase) in the pathway catalyzing the release of CO2 from fructose, only
      glucose-6-P dehydrogenase was deactivated by light and by dithiothreitol.

PMID- 12231785
TI  - Expression of Engineered Nuclear Male Sterility in Brassica napus (Genetics,
      Morphology, Cytology, and Sensitivity to Temperature).
AB  - A dominant genetic male sterility trait obtained through transformation in
      rapeseed (Brassica napus) was studied in the progenies of 11 transformed plants.
      The gene conferring the male sterility consists of a ribonuclease gene under the
      control of a tapetum-specific promoter. Two ribonuclease genes, RNase T1 and
      barnase, were used. The chimaeric ribonuclease gene was linked to the bialophos
      resistance gene, which confers resistance to the herbicide phosphinotricine
      (PPT). The resistance to the herbicide was used as a dominant marker for the male
      sterility trait. The study presented here concerns three aspects of this
      engineered male sterility: genetics correlated with the segregation of the T-DNA
      in the progenies; expression of the male sterility in relation to the morphology
      and cytology of the androecium; and stability of the engineered male sterility
      under different culture conditions. Correct segregation, 50% male-sterile, PPT
      resistant plants, and 50% male-fertile, susceptible plants were observed in the
      progeny of seven transformants. The most prominent morphological change in the
      male-sterile flowers was a noticeable reduction in the length of the stamen
      filament. The first disturbances of microsporogenesis were observed from the free
      microspore stage and were followed by a simultaneous degeneration of microspore
      and tapetal cell content. At anthesis, the sterile anthers contained only empty
      exines. In some cases, reversion to fertility of male-sterile plants has been
      observed. Both ribonuclease genes are susceptible to instability. Instability of
      the RNase T1-male sterility trait increased at temperatures higher than 25[deg]
      C. Our results do not allow us to confirm this observation for the barnase male
      sterile plants. However, the male-sterile plants of the progeny of two
      independent RNase T1 transformants were stably male sterile under all conditions
      studied.

PMID- 12231786
TI  - Water Transport in Onion (Allium cepa L.) Roots (Changes of Axial and Radial
      Hydraulic Conductivities during Root Development).
AB  - The hydraulic architecture of developing onion (Allium cepa L. cv Calypso) roots
      grown hydroponically was determined by measuring axial and radial hydraulic
      conductivities (equal to inverse of specific hydraulic resistances). In the
      roots, Casparian bands and suberin lamellae develop in the endodermis and
      exodermis (equal to hypodermis). Using the root pressure probe, changes of
      hydraulic conductivities along the developing roots were analyzed with high
      resolution. Axial hydraulic conductivity (Lx) was also calculated from stained
      cross-sections according to Poiseuille's law. Near the base and the tip of the
      roots, measured and calculated Lx values were similar. However, at distances
      between 200 and 300 mm from the apex, measured values of Lx were smaller by more
      than 1 order of magnitude than those calculated, probably because of remaining
      cross walls between xylem vessel members. During development of root xylem, Lx
      increased by 3 orders of magnitude. In the apical 30 mm (tip region), axial
      resistance limited water transport, whereas in basal parts radial resistances
      (low radial hydraulic conductivity, Lpr) controlled the uptake. Because of the
      high axial hydraulic resistance in the tip region, this zone appeared to be
      "hydraulically isolated" from the rest of the root. Changes of the Lpr of the
      roots were determined by measuring the hydraulic conductance of roots of
      different length and referring these data to unit surface area. At distances
      between 30 and 150 mm from the root tip, Lpr was fairly constant (1.4 x 10-7 m s
      1 MPa-1). In more basal root zones, Lpr was considerably smaller and varied
      between roots. The low contribution of basal zones to the overall water uptake
      indicated an influence of the exodermal Casparian bands and/or suberin lamellae
      in the endodermis or exodermis, which develop at distances larger than 50 to 60
      mm from the root tip.

PMID- 12231787
TI  - Further Evidence for Stachyose and Sucrose/H+ Antiporters on the Tonoplast of
      Japanese Artichoke (Stachys sieboldii) Tubers.
AB  - Vacuoles of Japanese artichoke (Stachys sieboldii) tubers accumulate up to 180 mM
      stachyose ([alpha]-galactose-[1->6]-[alpha]-galactose-[1->6]-[alpha]-glucose-[1 <
      >2]-[beta]-fructose) against a concentration gradient, probably by means of an
      active stachyose/H+ antiporter situated on the tonoplast. The goal of this study
      was to use isolated tonoplast vesicles to provide further evidence for the
      existence of such a transport mechanism. Therefore, vesicles were prepared from
      purified vacuoles of dormant tubers. ATP- and pyrophosphate (PPi)-dependent
      fluorescence quenching of the [delta]pH probe 9-amino-6-chloro-2-methoxyacridine
      (ACMA) indicated that these vesicles were capable of building up a pH gradient
      ([delta]pH, inside acid). The potent V-type H+-ATPase inhibitor bafilomycin
      prevented the formation of a [delta]pH in the vesicles. Bafilomycin (as well as
      nitrate, but not vanadate) also inhibited ATP hydrolysis, confirming the
      tonoplast origin of the isolated vesicles. Addition of stachyose (or sucrose, but
      not of mannitol) to energized vesicles caused a recovery of ACMA fluorescence,
      indicating a sugar-dependent dissipation of [delta]pH. The rate of fluorescence
      recovery was dependent on the external sugar concentration used. It displayed a
      single saturable response to increasing sugar concentrations. Apparent Km values
      of 52 and 25 mM were computed for stachyose and sucrose antiporter activities,
      respectively. It was also demonstrated that energized vesicles showed a much
      higher rate of [14C]stachyose (3 mM) and [14C]sucrose (1 mM) uptake than
      deenergized vesicles. The results obtained with isolated tonoplast vesicles were
      very similar to those obtained earlier with intact vacuoles and, therefore,
      confirm the existence of active stachyose and sucrose/H+ antiporters on the
      tonoplast of Stachys tuber vacuoles.

PMID- 12231788
TI  - Photochemical and Nonphotochemical Fluorescence Quenching Processes in the Diatom
      Phaeodactylum tricornutum.
AB  - Nonphotochemical fluorescence quenching was found to exist in the dark-adapted
      state in the diatom Phaeodactylum tricornutum. Pretreatment of cells with the
      uncoupler carbonylcyanide m-chlorophenylhydrazone (CCCP) or with nigericin
      resulted in increases in dark-adapted minimum and maximum fluorescence yields.
      This suggests that a pH gradient exists across the thylakoid membrane in the
      dark, which serves to quench fluorescence levels nonphotochemically. The
      physiological processes involved in establishing this proton gradient were
      sensitive to anaerobiosis and antimycin A. Based on these results, it is likely
      that this energization of the thylakoid membrane is due in part to
      chlororespiration, which involves oxygen-dependent electron flow through the
      plastoquinone pool. Chlororespiration has been shown previously to occur in
      diatoms. In addition, we observed that cells treated with 3-(3,4-dichlorophenyl)
      1,1-dimethylurea exhibited very strong nonphotochemical quenching when
      illuminated with actinic light. The rate and extent of this quenching were light
      intensity dependent. This quenching was reversed upon addition of CCCP or
      nigericin and was thus due primarily to the establishment of a pH gradient across
      the thylakoid membrane. Preincubation of cells with CCCP or nigericin or
      antimycin A completely abolished this quenching. Cyclic electron transport
      processes around photosystem I may be involved in establishing this proton
      gradient across the thylakoid membrane under conditions where linear electron
      transport is inhibited. At steady state under normal physiological conditions,
      the qualitative changes in photochemical and nonphotochemical fluorescence
      quenching at increasing photon flux densities were similar to those in higher
      plants. However, important quantitative differences existed at limiting and
      saturating intensities. Dissimilarities in the factors that regulate fluorescence
      quenching mechanisms in these organisms may account for these differences.

PMID- 12231789
TI  - Influence of Temperature on Proton Secretion and Hexacyanoferrate (III) Reduction
      of Zea mays L. Roots.
AB  - Responses of potassium hexacyanoferrate (III) [HCF(III)] reduction and net proton
      secretion by Zea mays L. cv Goldprinz roots to changes in ambient temperature
      were investigated. Arrhenius plots of proton secretion and redox activity showed
      a constant slope between 5 and 20[deg]C, indicating that reaction kinetics do not
      change. Proton secretion without HCF(III) was strongly temperature dependent.
      This dependence was not altered when H+ efflux was stimulated by fusicoccin or by
      increased K+ concentration. The temperature coefficient for HCF(III) reduction
      was low, indicating that the velocity of this reaction was limited by apoplastic
      diffusion of the ferric complex. In the presence of HCF(III) but not
      hexacyanoferrate (II), temperature dependence of proton efflux markedly declined,
      indicating fundamental changes in the process(es) contributing to net proton
      secretion. It is concluded that HCF(III) establishes a proton extrusion path that
      is directly linked with the reduction reaction.

PMID- 12231790
TI  - Modification of Rubisco and Altered Proteolytic Activity in O3-Stressed Hybrid
      Poplar (Populus maximowizii x trichocarpa).
AB  - Exposing hybrid poplar (Populus maximowizii x trichocarpa) plants to ozone (O3)
      resulted in an acceleration of the visual symptoms of senescence and a decrease
      in the activity and quantity of ribulose-1,5-bisphosphate carboxylase/oxygenase
      (Rubisco). Whole plants, crude leaf extracts, and isolated intact chloroplasts of
      hybrid poplar clone 245 were used to test the hypothesis that O3-induced
      structural modifications of Rubisco affect the activity of this key
      photosynthetic enzyme. Proteolytic activity, per se, could not account for losses
      in Rubisco; acidic and alkaline protease activities declined or were unaffected
      in foliage of O3-treated poplar saplings. In vitro treatment of leaf extracts
      with O3 decreased total Rubisco activity and binding of the enzyme's transition
      state analog, 2-carboxyarabinitol bisphosphate. Additionally, O3 increased the
      loss of Rubisco large subunit (LSU) when extracts were incubated at 37[deg]C.
      Treatment of isolated intact chloroplasts with O3 accelerated both the loss of
      the 55-kD Rubisco LSU and the accumulation of Rubisco LSU aggregates, as
      visualized by immunoblotting. The time-dependent modification in Rubisco
      structure was the primary response of the isolated organelles to O3 treatment,
      with little proteolytic degradation of the LSU detected.

PMID- 12231791
TI  - Induction of UDP-Glucose:Salicylic Acid Glucosyltransferase Activity in Tobacco
      Mosaic Virus-Inoculated Tobacco (Nicotiana tabacum) Leaves.
AB  - Salicylic acid (SA) is a putative signal that activates plant resistance to
      pathogens. SA levels increase systemically following the hypersensitive response
      produced by tobacco mosaic virus (TMV) inoculation of tobacco (Nicotiana tabacum
      L. cv Xanthi-nc) leaves. The SA increase in the inoculated leaf coincided with
      the appearance of a [beta]-glucosidase-hydrolyzable SA conjugate identified as
      [beta]-O-D-glucosylsalicylic acid (GSA). SA and GSA accumulation in the TMV
      inoculated leaf paralleled the increase in the activity of a UDP
      glucose:salicylic acid 3-O-glucosyltransferase (EC 2.4.1.35) ([beta]-GTase)
      capable of converting SA to GSA. Healthy tissues had constitutive [beta]-GTase
      activity of 0.076 milliunits g-1 fresh weight. This activity started to increase
      48 h after TMV inoculation, reaching its maximum (6.7-fold induction over the
      basal levels) 72 h after TMV inoculation. No significant GSA or elevated [beta]
      Gtase activity could be detected in the healthy leaf immediately above the TMV
      inoculated leaf. The effect of TMV inoculation on the [beta]-GTase and GSA
      accumulation could be duplicated by infiltrating tobacco leaf discs with SA at
      the levels naturally produced in TMV-inoculated leaves (2.7-27.0 [mu]g g-1 fresh
      weight). Pretreatment of leaf discs with the protein synthesis inhibitor
      cycloheximide inhibited the induction of [beta]-GTase by SA and prevented the
      formation of GSA. Of 12 analogs of SA tested, only 2,6-dihydroxybenzoic acid
      induced [beta]-GTase activity.

PMID- 12231792
TI  - Induction of Pyrophosphate-Dependent Phosphofructokinase in Watermelon (Citrullus
      lanatus) Cotyledons Coincides with Insufficient Cytosolic D-Fructose-1,6
      Bisphosphate 1-Phosphohydrolase to Sustain Gluconeogenesis.
AB  - During germination of Citrullus lanatus, pyrophosphate-dependent
      phosphofructokinase (PFP) activity is induced. The peak of PFP activity coincides
      with the maximum gluconeogenic flux and high fructose-2,6-bisphosphate (Fru-2,6
      P2) concentrations. Determination of cytosolic fructose-1,6 bisphosphatase
      (FBPase) activity in crude extracts is unreliable because of the high PFP
      activity. The FBPase activity, after correction for the contaminating PFP, is
      only one-third of the PFP activity. Purified cytosolic FBPase is inhibited by Fru
      2,6-P2. The low cytosolic FBPase activity and high Fru-2,6-P2 most probably
      result in inadequate in vivo activity to catalyze the observed gluconeogenic
      flux. The total PFP activity is sufficient to catalyze the required carbon flux.

PMID- 12231793
TI  - Control of Plant Virus Diseases by Pathogen-Derived Resistance in Transgenic
      Plants.

PMID- 12231794
TI  - Direct Demonstration of a Growth-Induced Water Potential Gradient.
AB  - When transpiration is negligible, water potentials in growing tissues are less
      than those in mature tissues and have been predicted to form gradients that move
      water into the enlarging cells. To determine directly whether the gradients
      exist, we measured water potentials along the radius of stems of intact soybean
      (Glycine max [L.] Merr.) seedlings growing in vermiculite in a water-saturated
      atmosphere. The measurements were made in individual cells by first determining
      the turgor with a miniature pressure probe, then determining the osmotic
      potential of solution from the same cell, and finally summing the two potentials.
      The osmotic potentials were corrected for sample mixing in the probe. The
      measurements were checked with a thermocouple psychrometer that gave average
      tissue water potentials. In the elongating region, the water potential was
      highest near the xylem and lowest near the epidermis and in the center of the
      pith. In the basal, more mature region of the same stems, water potentials were
      near zero next to the xylem and throughout the tissue. These basal potentials
      reflected mostly the potential of the xylem, which extended into the elongating
      tissues. Thus, the high basal potential confirmed the high potential near the
      xylem in the elongating tissues. The psychrometer measurements for each tissue
      gave average potentials that agreed with the average of the cell potentials from
      the pressure probe. We conclude that a radial gradient was present in the
      elongating region that formed a water potential field in three dimensions around
      the xylem and that confirmed the predictions of Molz and Boyer (F.J. Molz and
      J.S. Boyer [1978] Plant Physiol 62: 423-429).

PMID- 12231795
TI  - Regulation of Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase Activity in
      Response to Reduced Light Intensity in C4 Plants.
AB  - The light-dependent regulation of ribulose-1,5-bisphosphate carboxylase/oxygenase
      (Rubisco) activity was studied in 16 species of C4 plants representing all three
      biochemical subtypes and a variety of taxonomic groups. Rubisco regulation was
      assessed by measuring (a) the ratio of initial to total Rubisco activity, which
      reflects primarily the carbamylation state of the enzyme, and (b) total Rubisco
      activity per mol of Rubisco catalytic sites, which declines when 2
      carboxyarabinitol 1-phosphate (CA1P) binds to carbamylated Rubisco. In all
      species examined, the activity ratio of Rubisco declined with a reduction in
      light intensity, although substantial variation was apparent between species in
      the degree of Rubisco deactivation. No relationship existed between the degree of
      Rubisco deactivation and C4 subtype. Dicots generally deactivated Rubisco to a
      greater degree than monocots. The total activity of Rubisco per catalytic site
      was generally independent of light intensity, indicating that CA1P and other
      inhibitors are not major contributors to the light-dependent regulation of
      Rubisco activity in C4 plants. The light response of the activity ratio of
      Rubisco was measured in detail in Amaranthus retroflexus, Brachiaria texana, and
      Zea mays. In A. retroflexus and B. texana, the activity ratio declined
      dramatically below a light intensity of 400 to 500 [mu]mol of photons m-2 s-1. In
      Z. mays, the activity ratio of Rubisco was relatively insensitive to light
      intensity compared with the other species. In A. retroflexus, the pool size of
      ribulose bisphosphate (RuBP) declined with reduced light intensity except between
      50 and 500 [mu]mol m-2 s-1, when the activity ratio of Rubisco was light
      dependent. In Z. mays, by contrast, the pool size of RuBP was light dependent
      only below 350 [mu]mol m-2 s-1. These results indicate that, in response to
      changes in light intensity, most C4 species regulate Rubisco by reversible
      carbamylation of catalytic sites, as commonly observed in C3 plants. In a few
      species, notably Z. mays, Rubisco is not extensively regulated in response to
      changes in light intensity, possibly because the activity of the CO2 pump may
      become limiting for photosynthesis at subsaturating light intensity.

PMID- 12231796
TI  - Effect of Intracellular Glutathione Level on the Production of 6-Methoxymellein
      in Cultured Carrot (Daucus carota) Cells.
AB  - To produce phytoalexin, 6-methoxymellein (6-MM) was induced in suspension
      cultures of carrot (Daucus carota) by buthionine sulfoximine (BSO) and CuCl2.
      Addition of BSO (a specific inhibitor of glutathione [GSH] synthesis) to the
      cultures lowered the cellular GSH levels. This depletion of GSH was BSO
      concentration dependent, and the extent of 6-MM accumulation was dependent on the
      GSH depletion. The accumulation of 6-MM induced by BSO was suppressed by
      exogenous GSH. Exogenous H2O2 stimulated the production of 6-MM when added 1 d
      after BSO treatment, whereas H2O2 added at time zero or on the 4th d of BSO
      treatment did not. Moreover, a synergistic effect of simultaneous addition of BSO
      and CuCl2 was observed. These results suggest that active oxygen species may be
      involved in the triggering of 6-MM synthesis.

PMID- 12231797
TI  - Physiological and Environmental Requirements for Poplar (Populus deltoides) Bark
      Storage Protein Degradation.
AB  - In poplar (Populus deltoides Bartr. ex Marsh), a 32-kD bark storage protein (BSP)
      accumulates in the bark during autumn and winter and declines during spring shoot
      growth. We investigated the physiological and environmental factors necessary for
      the degradation of poplar BSP. Poplar plants were exposed to short-day (SD)
      photoperiods for either 28 or 49 d. Plants exposed to short days for 28 d formed
      a terminal bud but were not dormant, whereas exposure to short days for 49 d
      induced bud dormancy. BSP accumulated in bark of plants exposed to both SD
      treatments. The level of BSP declined rapidly when nondormant plants were
      returned to long days. BSP levels did not decline in dormant plants that were
      exposed to long-day (LD) conditions. If dormant plants were first treated with
      either low temperatures (0[deg]C for 28 d) or with 0.5 M H2CN2 to overcome
      dormancy and then returned to long days, the level of BSP declined. Removal of
      buds from non-dormant or dormant plants in which dormancy had been overcome
      inhibited the degradation of BSP in LD conditions. BSP mRNA levels rapidly
      declined in plants exposed to long days, irrespective of the dormancy status of
      the plants or the presence or absence of buds. These results indicate that the
      buds of poplars are somehow able to communicate with bark storage sites and
      regulate poplar BSP degradation. These results further support an association of
      BSP mRNA levels with photoperiod because short days stimulate BSP mRNA
      accumulation, whereas long days result in a decline of BSP mRNA abundance.

PMID- 12231798
TI  - Wheat (Triticum aestivum L.) [gamma]-Gliadin Accumulates in Dense Protein Bodies
      within the Endoplasmic Reticulum of Yeast.
AB  - Following their sequestration into the endoplasmic reticulum (ER), wheat storage
      proteins may either be retained and packaged into protein bodies within this
      organelle or transported via the Golgi to vacuoles. We attempted to study the
      processes of transport and packaging of wheat storage proteins using the
      heterologous expression system of yeast. A wild-type wheat [gamma]-gliadin,
      expressed in the yeast cells, accumulated mostly within the ER and was deposited
      in protein bodies with similar density to natural protein bodies from wheat
      endosperm. This suggested that wheat storage proteins contain sufficient
      information to initiate the formation of protein bodies in the ER of a
      heterologous system. Only a small amount of the [gamma]-gliadin was transported
      to the yeast vacuoles. When a deletion mutant of the [gamma]-gliadin, lacking the
      entire N-terminal repetitive region, was expressed in the yeast cells, the mutant
      was unable to initiate the formation of protein bodies within the ER and was
      completely transported to the yeast vacuole. This strongly indicated that the
      information for packaging into dense protein bodies within the ER resides in the
      N-terminal repetitive region of the [gamma]-gliadin. The advantage of using yeast
      to identify the signals and mechanisms controlling the transport of wheat storage
      proteins and their deposition in protein bodies is discussed.

PMID- 12231799
TI  - Aluminum Effects on Calcium (45Ca2+) Translocation in Aluminum-Tolerant and
      Aluminum-Sensitive Wheat (Triticum aestivum L.) Cultivars (Differential Responses
      of the Root Apex versus Mature Root Regions).
AB  - The influence of Al exposure on long-distance Ca2+ translocation from specific
      root zones (root apex or mature root) to the shoot was studied in intact
      seedlings of winter wheat (Triticum aestivum L.) cultivars (Al-tolerant Atlas 66
      and Al-sensitive Scout 66). Seedlings were grown in 100 [mu]M CaCl2 solution (pH
      4.5) for 3 d. Subsequently, a divided chamber technique using 45Ca2+-labeled
      solutions (100 [mu]M CaCl2 with or without 5 or 20 [mu]M AlCl3, pH 4.5) was used
      to study Ca2+ translocation from either the terminal 5 to 10 mm of the root or a
      10-mm region of intact root approximately 50 mm behind the root apex. The Al
      concentrations used, which were toxic to Scout 66, caused a significant
      inhibition of Ca2+ translocation from the apical region of Scout 66 roots. The
      same Al exposures had a much smaller effect on root apical Ca2+ translocation in
      Atlas 66. When a 10-mm region of the mature root was exposed to 45Ca2+, smaller
      genotypic differences in the Al effects effects on Ca2+ translocation were
      observed, because the degree of Al-induced inhibition of Ca2+ translocation was
      less than that at the root apex. Exposure of the root apex to Al inhibited root
      elongation by 70 to 99% in Scout 66 but had a lesser effect (less than 40%
      inhibition) in Atlas 66. When a mature root region was exposed to Al, root
      elongation was not significantly affected in either cultivar. These results
      demonstrate that genotypic differences in Al-induced inhibition of Ca2+
      translocation and root growth are localized primarily in the root apex. The
      pattern of Ca2+ translocation within the intact root was mainly basipetal, with
      most of the absorbed Ca2+ translocated toward the shoot. A small amount of
      acropetal Ca2+ translocation from the mature root regions to the apex was also
      observed, which accounted for less than 5% of the total Ca2+ translocation within
      the entire root. Because Ca2+ translocation toward the root apex is limited, most
      of the Ca2+ needed for normal cellular function in the apex must be absorbed from
      the external solution. Thus, continuous Al disruption of Ca2+ absorption into
      cells of the root apex could alter Ca2+ nutrition and homeostasis in these cells
      and could play a pivotal role in the mechanisms of Al toxicity in Al-sensitive
      wheat cultivars.

PMID- 12231801
TI  - Inositol Trisphosphate Metabolism in Subcellular Fractions of Barley (Hordeum
      vulgare L.) Mesophyll Cells.
AB  - Phosphatases in cytosolic fractions, vacuoles, and vacuolar membranes from barley
      (Hordeum vulgare L.) leaves were found to dephosphorylate inositol 1,4,5
      trisphosphate (IP3). 1,4-inositol bisphosphate (1,4-IP2) is the main product of
      IP3 dephosphorylation by the cytosolic fraction. The activity was strictly Mg2+
      dependent. In contrast, IP3 dephosphorylation activity of both the soluble
      vacuolar and the tonoplast fractions was inhibited up to 50% by Mg2+. When
      vacuolar membranes were incubated with IP3, 1,4-IP2 was produced only under
      neutral and slightly alkaline conditions. Under acidic conditions, however,
      dephosphorylation yielded putative 4,5-inositol bisphosphate. Li+ (20 mM) and
      Ca2+ (100 [mu]M) strongly inhibited activity in the soluble vacuolar fraction but
      had only a slight effect on the activities of the cytosolic and tonoplast
      fractions.

PMID- 12231800
TI  - Stomatal Opening Is Induced in Epidermal Peels of Commelina communis L. by GTP
      Analogs or Pertussis Toxin.
AB  - Pretreatment with pertussis toxin or microinjection of guanosine- 5[prime]-(3
      thiotriphosphate) (GTP-[gamma]-S) into guard cells in peeled epidermis of
      Commelina communis L. promoted stomatal opening under subsaturating white light.
      Guanosine-5[prime]-(2-thiodiphosphate) (GDP-[beta]-S) and adenosine-5[prime]-(3
      thiotriphosphate) (ATP-[gamma]-S) did not change stomatal aperture under
      identical conditions. These results indicate that G proteins may be involved in
      the regulation of stomatal opening.

PMID- 12231802
TI  - Changes in Lipid Peroxidation and Lipolytic and Free-Radical Scavenging Enzyme
      Activities during Aging and Sprouting of Potato (Solanum tuberosum) Seed-Tubers.
AB  - Previous research has shown that cell membranes of potato (Solanum tuberosum L.
      cv Russet Burbank) seed-tubers lose integrity between 7 and 26 months of storage
      (4[deg]C, 95% relative humidity), and this loss coincides with a significant
      decrease in growth potential. The age-induced decline in membrane integrity is
      apparently due to increased peroxidative damage of membrane lipids.
      Malondialdehyde (MDA) and ethane concentrations (sensitive markers of lipid
      peroxidation and membrane damage) increased in seed-tuber tissues with advancing
      age. Moreover, in vivo ethane production from discs of cortex tissue from 13- and
      25-month-old seed-tubers was 87% greater (on average) than that from discs from 1
      month-old tubers. Calcium suppressed ethane production from all ages of tissue
      discs, and the effect was concentration dependent. Linoleic acid enhanced ethane
      production from 5- and 17-month-old tubers by 61 and 228%, respectively,
      suggesting that older tissue may contain a higher free-radical (FR) titer and/or
      lower free polyunsaturated fatty acid content. In addition, throughout plant
      establishment, the internal ethane concentration of older seed-tubers was 54%
      higher than that of younger seed-tubers. MDA concentration of tuber tissue
      declined by about 65% during the initial 7 months of storage and then increased
      267% as tuber age advanced to 30 months. The age-induced trend in tuber reducing
      sugar concentration was similar to that of MDA, and the two were linearly
      correlated. The age-dependent increase in reducing sugars may thus reflect
      peroxidative degeneration of the amyloplast membrane, leading to increased starch
      hydrolysis. Compared with 5-month-old seed tubers, 17- and 29-month-old seed
      tubers had significantly higher levels of lipofuscin-like fluorescent compounds
      (FCs), which are produced when MDA reacts with free amino acids. Age-dependent
      increases in MDA, ethane, and FCs were not associated with higher activities of
      phospholipase and lipoxygenase in tissue from older tubers. In fact, 8-month-old
      seed-tubers had significantly higher activities of these enzymes than 20-month
      old seed-tubers. However, the activities of superoxide dismutase, peroxidase, and
      catalase in 20-month-old tubers were substantially higher out of storage, and
      increased at a faster rate during plant establishment, than in 8-month-old seed
      tubers. Collectively, these results suggest that a gradual build-up of FRs leads
      to peroxidative damage of membrane lipids during aging of potato seed-tubers.

PMID- 12231804
TI  - Monovalent Cation Activation of Plant Pyruvate Dehydrogenase Kinase.
AB  - The pyruvate dehydrogenase kinase-catalyzed inactivation of the pyruvate
      dehydrogenase complex was studied using dialyzed, soluble proteins from
      mitochondria purified from green leaf tissue of Pisum sativum L. seedlings. At
      subsaturating ATP concentrations, K+ or NH4+, but not Na+, stimulated the
      pyruvate dehydrogenase kinase by lowering the Km(ATP). Micromolar concentrations
      of NH4+ were required to produce the same effect as millimolar concentrations of
      K+. This is apparent from the observations that the activation constant (Kact)
      for NH4+ was 0.1 mM, whereas the Kact(K+) was 0.7 mM. Maximal pyruvate
      dehydrogenase kinase velocities attained with NH4+ were higher than those with
      K+, and, therefore, NH4+ was able to stimulate PDH kinase further in the presence
      of saturating K+. This result supports our conclusion that photorespiratory NH4+
      production in plant mitochondria may be involved in regulating the entry of
      carbon into the Krebs cycle by way of the pyruvate dehydrogenase complex.

PMID- 12231803
TI  - Group 3 Late Embryogenesis Abundant Proteins in Desiccation-Tolerant Seedlings of
      Wheat (Triticum aestivum L.).
AB  - Dormant seeds and young seedlings of wheat (Triticum aestivum L.) tolerate
      desiccation. A transcript expressed in this desiccation-tolerant tissue has been
      cloned and sequenced (J. Curry, C.F. Morris, M.K. Walker-Simmons [1991] Plant Mol
      Biol 16: 1073-1076). This wheat cDNA clone encodes a protein that is homologous
      to other group 3 late embryogenesis abundant (LEA) proteins. In this report, we
      describe the production of polyclonal antibodies to the protein product of the
      cDNA clone and assess group 3 LEA protein levels in desiccation-tolerant tissue.
      The group 3 LEA antibodies detected four major proteins in wheat with molecular
      masses from 27 to 30.5 kD. The genes for these proteins mapped to wheat
      chromosomes 1A, 1B, and 1D. The group 3 LEA proteins were present in mature seed
      embryos and were maintained when growth-arrested, dormant seeds were hydrated for
      111 h. However, in germinating seeds the group 3 LEA proteins declined and were
      no longer detectable by 111 h. We severely dehydrated seedlings (more than 90%
      water loss) to assess group 3 LEA transcript and protein accumulation in tissues
      of these desiccation-tolerant plants. In response to dehydration, abscisic acid
      (ABA) levels increased dramatically and group 3 LEA mRNAs were induced in root,
      shoot, and scutellar tissue. However, group 3 LEA proteins were detected only in
      shoot and scutellar tissue and not in root tissue. Treatment of nonstressed
      seedlings with 20 [mu]M ABA resulted in low levels of group 3 LEA proteins in the
      roots, whereas higher levels were found in the shoot and scutellar tissue. When
      dehydrated seedlings were rehydrated, shoot and scutellar tissue resumed growth.
      The roots did not resume growth and subsequently died. New roots developed later
      from the scutellar tissue. Thus, in severely dehydrated wheat seedlings, the
      accumulation of high levels of group 3 LEA proteins is correlated with tissue
      dehydration tolerance.

PMID- 12231805
TI  - DNA Strand-Transfer Activity in Pea (Pisum sativum L.) Chloroplasts.
AB  - The occurrence of DNA recombination in plastids of higher plants is well
      documented. However, little is known at the enzymic level. To begin dissecting
      the biochemical mechanism(s) involved we focused on a key step: strand transfer
      between homologous parental DNAs. We detected a RecA-like strand transfer
      activity in stromal extracts from pea (Pisum sativum L.) chloroplasts. Formation
      of joint molecules requires Mg2+, ATP, and homologous substrates. This activity
      is inhibited by excess single-stranded DNA (ssDNA), suggesting a necessary
      stoichiometric relation between enzyme and ssDNA. In a novel assay with Triton X
      100-permeabilized chloroplasts, we also detected strand invasion of the
      endogenous chloroplast DNA by 32P-labeled ssDNA complementary to the 16S rRNA
      gene. Joint molecules, analyzed by electron microscopy, contained the expected
      displacement loops.

PMID- 12231806
TI  - Purification and Characterization of Membrane-Bound Inositol Phospholipid
      Specific Phospholipase C from Suspension-Cultured Rice (Oryza sativa L.) Cells
      (Identification of a Regulatory Factor).
AB  - A membrane-bound inositol phospholipid-specific phospholipase C was solubilized
      from rice (Oryza sativa L.) microsomal membranes and purified to apparent
      homogeneity using a series of chromatographic separations. The apparent molecular
      mass of the enzyme was estimated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis to be 42,000 D, and the isoelectric point was 5.1. The optimum pH
      for the enzyme activity was approximately 6.5, and the enzyme was activated by
      both Ca2+ and Sr2+. The chemical and catalytic properties of the purified
      membrane-bound phospholipase C differed from those of the soluble enzyme reported
      previously (K. Yotsushima, K. Nakamura, T. Mitsui, I. Igaue [1992] Biosci Biotech
      Biochem 56: 1247-1251). In addition, we found a regulatory factor for the
      phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolyzing activity of
      phospholipase C from rice cells. The regulatory factor was dissociated from the
      catalytic subunit of phospholipase C during the purification. The regulatory
      factor was necessary to induce PIP2-hydrolyzing activity of both membrane-bound
      and -soluble phospholipase C; these purified enzymes had no activity alone.
      Because the plasma membranes isolated from rice cells could also act as a
      regulatory factor, the regulatory factor seems to be localized in the plasma
      membranes. Regulation of inositol phospholipid turnover in rice cells is
      discussed.

PMID- 12231807
TI  - Metabolism of Transpired Ethanol by Eastern Cottonwood (Populus deltoides
      Bartr.).
AB  - Ethanol has previously been shown to be present in the xylem sap of flooded and
      nonflooded trees. Because of the constitutive presence of alcohol dehydrogenase
      in the mature leaves of woody plants, we hypothesized that the leaves and shoots
      of trees had the ability to metabolize ethanol supplied by the transpiration
      stream. 1-[14C]Ethanol was supplied to excised leaves and shoots of eastern
      cottonwood (Populus deltoides Bartr.) in short- and long-term experiments. More
      than 99% of the radiolabel was incorporated into plant tissue in short-term
      experiments, with more than 95% of the label remaining in plant tissue after 24
      h. In all experiments, less than 5% of the label was transpired as ethanol and
      less than 1% was emitted as CO2. In excised leaf experiments, less than 0.5% of
      the radiolabel escaped from the leaf. Fifty percent of the label was incorporated
      into the petioles of excised leaves; 56% was incorporated into the stems of
      excised shoots. Very little label reached the leaf mesophyll cells of excised
      shoots, as revealed by autoradiography. Radiolabel appeared primarily in the
      water- and chloroform-soluble fractions in short-term experiments, whereas in
      long-term experiments, label was also incorporated into protein. These results
      demonstrate that the leaves and stems of trees appear to have substantial ability
      to scavenge ethanol from the transpiration stream, allowing efficient recovery of
      ethanol produced elsewhere by hypoxic tissues. When labeled ethanol was supplied
      to excised petioles in a 5-min pulse, 41% of the label was incorporated into
      organic acids. Some label was also incorporated into amino acids, protein, and
      the chloroform-soluble fraction, with very little appearing in neutral sugars,
      starch, or the insoluble pellet. Labeled organic acids were separated by high
      performance liquid chromatography and were composed of acetate, isocitrate,
      [alpha]-ketoglutarate, and succinate. There was no apparent incorporation of
      label into phosphorylated compounds. We conclude that, in higher plants, ethanol
      is metabolized to acetaldehyde and then to acetate by alcohol and aldehyde
      dehydrogenases, and then into general metabolism.

PMID- 12231808
TI  - Dynamics of Photosystem Stoichiometry Adjustment by Light Quality in
      Chloroplasts.
AB  - Long-term imbalance in light absorption and electron transport by photosystem I
      (PSI) and photosystem II (PSII) in chloroplasts brings about changes in the
      composition, structure, and function of thylakoid membranes. The response entails
      adjustment in the photosystem ratio, which is optimized to help the plant retain
      a high quantum efficiency of photosynthesis (W.S. Chow, A. Melis, J.M. Anderson
      [1990] Proc Nat Acad Sci USA 87: 7502-7506). The dynamics of photosystem ratio
      adjustment were investigated upon the transfer of pea {Pisum sativum} plants from
      a predominantly PSI-light to a predominantly PSII-light environment and vice
      versa. The concentration of functional components (primary electron accepting
      plastoquinone of PSII [QA], P700) and that of constituent proteins were monitored
      during acclimation by A difference spectrophotometry and immunoblot analysis,
      respectively. Fully reversible changes in photosystem ratio occurred with a half
      time of about 20 h. They involved closely coordinated changes in the
      concentration of the QA, reaction center protein D1, D2, and the 9-kD apoprotein
      of the cytochrome b559 for PSII. Similarly, closely coordinated changes in the
      relative concentration of P700 and reaction center proteins of PSI were observed.
      The level of chlorophyll b and that of the light-harvesting complex II changed in
      accordance with the concentration of PSII in the acclimating thylakoids. Overall,
      adjustments in the photosystem ratio in response to PSI- or PSII-light conditions
      appeared to be a well-coordinated reaction in the chloroplast. The response was
      absent in the chlorophyll b-less chlorina f2 mutant of barley (Hordeum vulgare)
      and in a phycobilisomeless mutant of Agmenellum quadruplicatum, suggesting that
      photosystem accessory pigments act as the light-quality perception molecules and
      that PSI and PSII themselves play a role in the signal transduction pathway.

PMID- 12231809
TI  - Cyclic [beta]-1,6 -1,3 Glucans Are Synthesized by Bradyrhizobium japonicum
      Bacteroids within Soybean (Glycine max) Root Nodules.
AB  - We have previously reported that free-living cultures of Bradyrhizobium species
      produce novel oligosaccharides that are cyclic, contain between 10 and 13 glucose
      residues, and are linked by [beta]-1,6 and [beta]-1,3 glycosidic bonds (K.J.
      Miller, R.S. Gore, R. Johnson, A.J. Benesi, V.N. Reinhold [1990] J Bacteriol 172:
      136-142). In the present study, we show that these glucans are also synthesized
      by bacteroids of Bradyrhizobium japonicum USDA 110 within Glycine max root
      nodules.

PMID- 12231810
TI  - Aleurones from a Barley with Low [alpha]-Amylase Activity Become Highly
      Responsive to Gibberellin When Detached from the Starchy Endosperm.
AB  - The physiological and molecular bases for contrasting [alpha]-amylase phenotypes
      were examined in germinating seeds of two barley (Hordeum vulgare L.) cultivars,
      Morex and Steptoe. Morex is a high-quality malting barley that develops high
      [alpha]-amylase activity soon after germination. Steptoe is a feed barley that
      develops only low [alpha]-amylase activity levels during this period. The
      expression of all high- and low-isoelectric point (pl) [alpha]-amylase isozymes
      is reduced in Steptoe. The amount of [alpha]-amylase mRNA per gram of seedling
      tissue is correspondingly lower in Steptoe. Southern blot analysis revealed that
      the cultivars have the same copy number and organization for most high- and low
      pl genes. Steptoe seedlings or embryoless half-seeds produce little [alpha]
      amylase in response to exogenous applications of gibberellic acid (GA3) compared
      with Morex. However, when isolated aleurones of both cultivars are treated with
      GA3, they produce similar amounts of high- and low-pl [alpha]-amylase RNAs. This
      suggests that a factor in the starchy endosperm is responsible for lowered
      [alpha]-amylase response in Steptoe. The factor is probably not abscisic acid
      (ABA), since the two cultivars have similar concentrations of ABA during
      germination.

PMID- 12231811
TI  - Purification and Characterization of Geranyl Diphosphate Synthase from Vitis
      vinifera L. cv Muscat de Frontignan Cell Cultures.
AB  - A geranyl diphosphate synthase (EC 2.5.1.1), which catalyzes the formation of
      geranyl diphosphate from dimethylallyl diphosphate and isopentenyl diphosphate,
      was isolated from Vitis vinifera L. cv Muscat de Frontignan cell cultures.
      Purification of the enzyme was achieved successively by ammonium sulfate
      precipitation and chromatography on DEAE-Sephacel, hydroxylapatite, Mono Q,
      Phenyl Superose, Superose 12, and preparative nondenaturing polyacrylamide gels.
      The enzyme formed only geranyl diphosphate as a product. In all cases, neither
      neryl diphosphate, the cis isomer, nor farnesyl diphosphate was detected. The
      enzyme showed a native molecular mass of 68 [plus or minus] 5 kD as determined by
      gel permeation. On sodium dodecyl sulfate polyacrylamide gels, geranyl
      diphosphate synthase purified to electrophoretic homogeneity migrated with a
      molecular mass of 66 [plus or minus] 2 kD. Michaelis constants for isopentenyl
      diphosphate and dimethylallyl diphosphate were 8.5 and 56.8 [mu]M, respectively.
      The enzyme required Mn2+ and Mg2+ as cofactors and its activity was enhanced by
      Triton X-100. Inorganic pyrophosphate, aminophenylethyl diphosphate, and geranyl
      diphosphate had inhibitory effects on the enzyme.

PMID- 12231812
TI  - Modification of Phospholipid Catabolism in Microsomal Membranes of [gamma]
      Irradiated Cauliflower (Brassica oleracea L.).
AB  - Acceleration of membrane deterioration has been observed recently during storage
      of [gamma]-irradiated cauliflower (Brassica oleracea L., Botrytis group). In the
      present study, the activity of microsome-associated lipolytic enzymes was
      investigated in cauliflower florets exposed to 0 or 4 kilograys of [gamma]
      radiation and stored for 8 d at 13[deg]C. Radiolabeled breakdown products
      obtained from the metabolism of (16:0/18:2*)-phosphatidylcholine and (16:0/16:0)
      phosphatidyl-[N-methyl-3H]choline by microsomal membranes indicated that
      phospholipase D (EC 3.1.4.4), phosphatidic acid phosphatase (EC 3.1.3.4), and
      lipolytic acyl hydrolase were associated with the membranes. The rate of
      phosphatidylcholine catabolism by the membranes increased slowly in control
      cauliflower during storage. [gamma] irradiation caused an immediate rise in
      phosphatidylcholine catabolism that remained higher than that of the controls
      during subsequent storage. Collectively, the data suggest that enhancement of
      membrane lipolytic activity results from free-radical-induced stress. Rapid
      increase of the membrane-associated phospholipase D activity may be a key event
      leading to accelerated membrane deterioration following [gamma] irradiation.

PMID- 12231813
TI  - Endopolygalacturonase in Apples (Malus domestica) and Its Expression during Fruit
      Ripening.
AB  - The activity of polygalacturonase (PG) has been detected in ripe McIntosh apples
      (Malus domestica Borkh. cv McIntosh) both by enzyme activity measurement and
      immunoblotting using an anti-tomato-PG antibody preparation. PG activity
      increased during fruit ripening and remained steady, or decreased slightly, after
      5 months of controlled atmospheric storage. The enzyme had a relative molecular
      weight of 45,000 as determined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and 56,000 to 61,000 when determined by gel filtration. Viscosity
      and reducing end group measurements with a commercial pectin preparation showed
      that the enzyme is endo acting. In RNA and DNA blot hybridization experiments, a
      full-length tomato PG cDNA hybridized with the apple RNA and DNA, showing the
      identity of genes encoding the activity of the enzyme in tomato and apple.

PMID- 12231814
TI  - Characterization of the Oligogalacturonide-Induced Oxidative Burst in Cultured
      Soybean (Glycine max) Cells.
AB  - The rapid release of H2O2 by elicited plant cells, recently termed the oxidative
      burst, was investigated in suspension-cultured soybean (Glycine max Merr. cv
      Kent) cells stimulated with a purified polygalacturonic acid (PGA) elicitor.
      Examination of the elicited cells by fluorescence microscopy revealed that
      virtually every living cell participates in the elicitor-induced H2O2 burst.
      Measurement of the kinetics of the response using a macroscopic fluorescence
      based assay indicated that approximately 100 molecules of H2O2 are generated per
      PGA molecule added, achieving a cumulative H2O2 concentration of approximately
      1.2 mmol L-1 of packed cells. At the height of the defense response, 3 x 10-14
      mol of H2O2 cell-1 min-1 are produced, a value comparable to the rate of H2O2
      production by myeloid cells of mammals. Variables affecting the rate and
      magnitude of the soybean oxidative burst were found to be mechanical stress,
      extracellular pH, and cell age. The PGA-induced oxidative burst was shown to
      undergo both homologous and heterologous desensitization, a characteristic of
      signal transduction pathways in animals. Homologous desensitization was obtained
      with PGA, and heterologous desensitization was observed with the G protein
      activator mastoparan, consistent with earlier observations showing that G
      proteins perform a regulatory function in this pathway. Finally, a model
      describing the possible role of the PGA-induced oxidative burst in the overall
      scheme of plant defense is proposed.

PMID- 12231815
TI  - Aspects of Subunit Interactions in the Chloroplast ATP Synthase (I. Isolation of
      a Chloroplast Coupling Factor 1-Subunit III Complex from Spinach Thylakoids).
AB  - A chloroplast ATP synthase complex (CF1 [chloroplast-coupling factor 1]-CF0
      [membrane-spanning portion of chloroplast ATP synthase]) depleted of all CF0
      subunits except subunit III (also known as the proteolipid subunit) was purified
      to study the interaction between CF1 and subunit III. Subunit III has a putative
      role in proton translocation across the thylakoid membrane during
      photophosphorylation; therefore, an accurate model of subunit inter-actions
      involving subunit III will be valuable for elucidating the mechanism and
      regulation of energy coupling. Purification of the complex from a crude CF1-CF0
      preparation from spinach (Spinacia oleracea) thylakoids was accomplished by
      detergent treatment during anion-exchange chromatography. Subunit III in the
      complex was positively identified by amino acid analysis and N-terminal
      sequencing. The association of subunit III with CF1 was verified by linear
      sucrose gradient centrifugation, immunoprecipitation, and incorporation of the
      complex into asolectin liposomes. After incorporation into liposomes, CF1 was
      removed from the CF1-III complex by ethylenediaminetetracetate treatment. The
      subunit III-proteoliposomes were competent to rebind purified CF1. These results
      indicate that subunit III directly interacts with CF1 in spinach thylakoids.

PMID- 12231816
TI  - Aspects of Subunit Interactions in the Chloroplast ATP Synthase (II.
      Characterization of a Chloroplast Coupling Factor 1-Subunit III Complex from
      Spinach Thylakoids).
AB  - A complex between chloroplast-coupling factor 1 (CF1) and subunit III of the
      membrane-spanning portion of the chloroplast ATP synthase (CF0), isolated as
      described in the accompanying paper (C.M. Wetzel and R.E. McCarty [1993] Plant
      Physiol 102: 241-249), has been further characterized. A comparison of the ATPase
      activities of CF1, CF1-subunit III, and the chloroplast ATP synthase (CF1-CF0)
      holoenzyme revealed that the properties of CF1-subunit III more closely resemble
      those of CF1-CF0 than those of CF1. In particular, the Ca2+-ATPase activity after
      reduction of the enzyme with dithiothreitol was much lower in CF1-subunit III and
      CF1-CF0 than in CF1, suggesting that the association of the inhibitory [epsilon]
      subunit is tightened by the presence of either CF0 or subunit III. Cold stability
      is a property of CF1-CF0 in thylakoid membranes. The ATPase activity of CF1
      incubated in the cold in the presence of asolectin liposomes was lost more
      rapidly than that of either CF1-subunit III or CF1-CF0 incorporated into
      liposomes. Removal of the [epsilon] subunit from all three preparations resulted
      in marked stimulation of their ATPase activity. Although subunit III was also
      removed during depletion of the [epsilon] subunit, it is not known whether the
      two subunits interact directly. CF1 deficient in the [epsilon] subunit binds to
      liposomes containing either subunit III or CF0. Taken together, these results
      provide evidence that the association of CF1 and subunit III of CFo is specific
      and may play a role in enzyme regulation.

PMID- 12231817
TI  - Chloroplast Inner-Envelope ATPase Acts as a Primary H+ Pump.
AB  - The stromal pH of the chloroplast must be maintained higher than that of the
      surrounding cytosol for photosynthetic carbon assimilation to occur. Experimental
      evidence demonstrating how this is accomplished in the plant cell is lacking. In
      the experiments reported here, we studied H+ and K+ flux across membranes of
      purified chloroplast inner-envelope vesicles. We were able to demonstrate ATP
      dependent transport of both cations across the membranes of these vesicles. The
      data presented document the presence of an H+-pump ATPase in the chloroplast
      envelope. Energy-dependent K+ flux across these membranes occurs as a consequence
      of primary H+ pumping. The H+-pumping activity demonstrated in this report is
      consistent with a model involving the activity of this envelope ATPase as a
      primary mechanism facilitating a stroma:cytosol [delta]pH.

PMID- 12231818
TI  - Isolation and Initial Characterization of Arabidopsis Mutants That Are Deficient
      in Phytochrome A.
AB  - Phytochrome, a red/far-red-light photoreceptor protein of plants, is encoded by a
      small gene family. Phytochrome A (PHYA), the product of the PHYA gene, is the
      predominant molecular species of phytochrome in etiolated tissue and has been
      best characterized biochemically. To define a role for PHYA, we isolated new
      mutants, designated fre1 (far-red elongated), in Arabidopsis thaliana that were
      specifically deficient in PHYA spectral activity and protein accumulation. These
      mutants were identified on the basis of their long hypocotyl phenotype under
      continuous far-red light. Although the fre1 mutants lacked the hypocotyl response
      to continuous far-red light, their responses to continuous white light and to end
      of-day far-red-light treatments were normal. Thus, PHYA appears to play only a
      minor role in the regulation of hypocotyl elongation under natural conditions. In
      contrast, the fre1 mutation affected greening a fre1 mutant was less able than
      the wild type to deetiolate after growth in the dark. However, the potentiation
      effect of a red-light pulse on accumulation of chlorophyll was not changed
      significantly in the fre1 mutants. Thus, the function of PHYA might be highly
      specialized and restricted to certain phases of Arabidopsis development.

PMID- 12231819
TI  - Visualizing Enzyme Secretion from Individual Barley (Hordeum vulgare) Aleurone
      Protoplasts.
AB  - A method was developed to detect [alpha]-amylase gene expression and [alpha]
      amylase secretion from individual barley (Hordeum vulgare L. cv Himalaya)
      aleurone protoplasts. Protoplasts are incubated in liquid media with or without
      hormones and embedded in a thin film of agarose and starch, where they remain
      viable for up to 24 h. [alpha]-Amylase secreted by individual protoplasts digests
      the starch, and starch hydrolysis is visualized after 45 min by staining the
      preparation with I2KI. After I2KI staining, secreting protoplasts are surrounded
      by a clear, starch-free halo visible by light microscopy. The formation of starch
      free halos is dependent on the synthesis and secretion of [alpha]-amylase and is
      not caused by carry-over of preformed enzyme from incubation media. Treating
      protoplasts with inhibitors of protein synthesis or exposing them to anaerobic
      conditions for 2 h before embedding them in agarose prevents the formation of
      halos. When [alpha]-amylase secretion is observed by counting the percentage of
      secreting protoplasts, the data are comparable to that obtained by measuring
      [alpha]-amylase secretion from a population of cells. The response of individual
      protoplasts to gibberellic acid (GA3) and abscisic acid measured by the thin-film
      method is almost identical to the response of populations of protoplasts to these
      hormones, validating the utility of this method. Although not generally practical
      for quantifying secretion, the thin-film method is uniquely useful in
      distinguishing secreting from nonsecreting protoplasts. In none of our
      experiments did more than 60% of the protoplasts secrete [alpha]-amylase when
      exposed to GA3, even though more than 95% of the protoplasts in the preparations
      were viable. Similar results were obtained when the response to GA3 was assayed
      at the level of gene transcription by visualizing the transient expression of a
      plasmid containing the promoter from [alpha]-amylase fused to the reporter gene
      glucuronidase in single protoplasts. The thin-film secretion assay also revealed
      that the response of a population of protoplasts to GA3 was not uniform with
      time. The effect of GA3 treatment was to gradually increase the percentage of
      responding protoplasts up to a maximum of 50 to 60%. Abscisic acid, which
      inhibits [alpha]-amylase secretion by GA3-treated protoplasts, reduced the
      proportion of protoplasts that secrete the enzyme.

PMID- 12231820
TI  - The Anti-nptII Gene (A Potential Negative Selectable Marker for Plants).
AB  - An efficient negative selection procedure is crucial to the isolation of rare
      homologous recombinants in gene targeting. Although gene targeting is a common
      practice in lower eukaryotes and is becoming routine in mammals, its application
      to plants has not been achieved. In this report, we have evaluated an antisense
      construct against the neomycin phosphotransferase gene (nptII) as a negative
      selectable marker. The anti-nptII gene construct was able to suppress nptII
      expression both transiently and in transformed tobacco (Nicotiana tabacum) calli.
      A construct was made which includes both a hygromycin-resistance gene and the
      sense plus antisense genes for neomycin phosphotransferase. Hygromy-cin-resistant
      calli were obtained after Agrobacterium-mediated transformation. Subsequently,
      hygromycin-resistant calli were tested for kanamycin sensitivity. The growth on
      kanamycin medium of calli harboring both the sense and antisense gene constructs
      was retarded, whereas that of control calli transformed with only the sense nptII
      gene was not inhibited. Southern blot analysis confirmed the presence of both
      nptII and anti-nptII genes. Northern blot analyses revealed that antisense
      transcripts of the nptII gene were made and that the level of sense transcripts
      was greatly reduced in transgenic calli. These results suggest that the anti
      nptII gene could potentially be used as a negative selectable marker for gene
      targeting in plants.

PMID- 12231821
TI  - Optimal Thermal Environments for Plant Metabolic Processes (Cucumis sativus L.)
      (Light-Harvesting Chlorophyll a/b Pigment-Protein Complex of Photosystem II and
      Seedling Establishment in Cucumber).
AB  - Analysis of the temperatures providing maximal photosystem II fluorescence
      reappearance following illumination and thermal kinetic windows (TKWs), obtained
      from the temperature characteristics of enzyme apparent Km values, have been
      proposed as indicators of the bounds of thermal stress in plants. In this study,
      we have evaluated the temperature optimum for the accumulation of the chlorophyll
      a/b light-harvesting complex of photosystem II (LHCP II), its mRNA, and the mRNA
      of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco)
      in cucumber (Cucumis sativus L. cv Ashley) as a broader measure of metabolism
      than that provided by either the fluorescence reappearance or TKWs. The TKW for
      cucumber is between 23.5 and 39[deg]C, with the minimum apparent Km occurring at
      32.5[deg]C. The photosystem II variable fluorescence reappearance following
      illumination was maximal between 30 and 35[deg]C. Maximum synthesis of the LHCP
      II occurred at 30[deg] C. The light-induced accumulation of the LHCP II and the
      small subunit of Rubisco mRNAs showed similar temperature characteristics.
      Suboptimal temperatures delayed germination, altered cotyledonary soluble sugar
      content, and broadened the temperature range for chlorophyll accumulation. These
      results demonstrate an effect of seed reserve mobilization on the range of
      temperatures for chlorophyll accumulation, and suggest that metabolic temperature
      characteristics may be broadened by increasing available substrates for enzyme
      utilization. This study provides new information about the relationship between
      TKWs and cellular responses to temperature. In addition, the results suggest that
      the temperature range outside of which plants experience temperature stress is
      narrower than traditionally supposed.

PMID- 12231822
TI  - RNA-Binding Protein from Arabidopsis.

PMID- 12231823
TI  - Notice of Retraction.

PMID- 12231824
TI  - Transduction of Blue-Light Signals.

PMID- 12231825
TI  - Mannose-6-Phosphate Reductase, a Key Enzyme in Photoassimilate Partitioning, Is
      Abundant and Located in the Cytosol of Photosynthetically Active Cells of Celery
      (Apium graveolens L.) Source Leaves.
AB  - Mannitol, a major photosynthetic product and transport carbohydrate in many
      plants, accounts for approximately 50% of the carbon fixed by celery (Apium
      graveolens L.) leaves. Previous subfractionation studies of celery leaves
      indicated that the enzymes for mannitol synthesis were located in the cytosol,
      but these data are inconsistent with that published for the sites of sugar
      alcohol synthesis in other families and taxa, including apple (Malus) and a brown
      alga (Fucus). Using antibodies to a key synthetic enzyme, NADPH-dependent mannose
      6-phosphate reductase (M6PR), and immunocytochemical techniques, we have resolved
      both the inter-cellular and intracellular sites of mannitol synthesis. In leaves,
      M6PR was found only in cells containing ribulose-1,5-bisphosphate
      carboxylase/oxygenase. M6PR was almost exclusively cytosolic in these cells, with
      the nucleus being the only organelle to show labeling. The key step in transport
      carbohydrate biosynthesis that is catalyzed by M6PR displays no apparent
      preferential association with vascular tissues or with the bundle sheath. These
      results show that M6PR and, thus, mannitol synthesis are closely associated with
      the distribution of photosynthetic carbon metabolism in celery leaves. The
      principal role of M6PR is, therefore, in the assimilation of carbon being
      exported from the chloroplast, and it seems unlikely that this enzyme plays even
      an indirect role in phloem loading of mannitol.

PMID- 12231826
TI  - Expression of the [beta]-Glucuronidase Gene in Pollen of Lily (Lilium
      longiflorum), Tobacco (Nicotiana tabacum), Nicotiana rustica, and Peony (Paeonia
      lactiflora) by Particle Bombardment.
AB  - A [beta]-glucuronidase (GUS) gene that is under the control of the anther
      specific LAT52 promoter of tomato (Lycopersicon esculentum) and the nopaline
      synthetase polyadenylation terminator was successfully expressed in pollen of
      Lilium longiflorum, Nicotiana tabacum, Nicotiana rustica, and Paeonia lactiflora
      using a pneumatic particle gun. The GUS gene in plasmid pBI221 was also
      expressed, to a lesser extent, in pollen of all of these species. The presence of
      methanol in the substrate solution for histochemical GUS assay and the incubation
      time in this solution influenced successful detection of GUS expression in
      bombarded pollen. Cytological analysis of GUS-expressing pollen of lily showed
      that introduced gold particles were seen in intracellular compartments of pollen,
      including the vegetative cytoplasm, vegetative nucleus, and generative cytoplasm.

PMID- 12231827
TI  - Hormonal Characterization of Transgenic Tobacco Plants Expressing the rolC Gene
      of Agrobacterium rhizogenes TL-DNA.
AB  - Transgenic tobacco (Nicotiana tabacum L. cv Wisconsin 38) plants expressing the
      Agrobacterium rhizogenes rolC gene under the control of the cauliflower mosaic
      virus 35S RNA promoter were constructed. These plants displayed several
      morphological alterations reminiscent of changes in indole-3-acetic acid (IAA),
      cytokinin, and gibberellin (GA) content. However, investigations showed that
      neither the IAA pool size nor its rate of turnover were altered significantly in
      the rolC plants. The biggest difference between rolC and wild-type plants was in
      the concentrations of the cytokinin, isopentenyladenosine (iPA) and the
      gibberellin GA19. Radio-immunoassay and liquid chromatography-mass spectrometry
      measurements revealed a drastic reduction in rolC plants of iPA as well as in
      several other cytokinins tested, suggesting a possible reduction in the synthesis
      rate of cytokinins. Furthermore, gas chromatography-mass spectrometry
      quantifications of GA19 showed a 5- to 6-fold increase in rolC plants compared
      with wild-type plants, indicating a reduced activity of the GA19 oxidase, a
      proposed regulatory step in the gibberellin biosynthesis. Thus, we conclude that
      RolC activity in transgenic plants leads to major alterations in the metabolism
      of cytokinins and gibberellins.

PMID- 12231828
TI  - Two Related Biosynthetic Pathways of Mugineic Acids in Gramineous Plants.
AB  - The biosynthesis of mugineic acids was studied by feeding 2H- or 13C-labeled
      compounds to water-cultured roots in several gramineous plants. The fate of
      labeled compounds was monitored by using 2H- and 13C-nuclear magnetic resonance.
      On investigating the proton changes during biosynthesis by feeding D,L-[3,3,4,4
      d4]-methionine (98.6% 2H), 2H-labeled 2[prime]-deoxymugineic, mugineic, and 3
      epihydroxymugineic acids were isolated from root washings of wheat (Triticum
      aestivum L. cv Minori), barley (Hordeum vulgare L. cv Minorimugi), and beer
      barley (Hordeum vulgare L. cv AM Nijo Tochigi), respectively. The 2H-nuclear
      magnetic resonance study indicated that 12 deuteriums were incorporated into the
      labeled 2[prime]-deoxymugineic acid, suggesting that three molecules of L
      [3,3,4,4-d4]methionine were combined. In comparison, one of the deuteriums at C
      2[prime] position in the mugineic acid, and one each of the deuteriums at C
      2[prime] and C-3 positions in the 3-epihydroxymugineic acid, were lost. However,
      all other deuteriums were incorporated in a manner similar to that of the labeled
      2[prime]-deoxymugineic acid. When [1,4[prime],4"-13C3]2[prime]-deoxymugineic acid
      (20% 13C) was fed to oat roots (Avena sativa L. cv Amuri II), avenic acid A,
      which was 13C enriched at the corresponding positions, was obtained. These
      results revealed that L-methionine was the precursor for all these mugineic acids
      and that cleavage of the azetidine ring or hydroxylation of the 2[prime]
      deoxymugineic acid produced two related biosynthetic pathways in different
      gramineous plant species: L-methionine -> 2[prime]-deoxymugineic acid -> avenic
      acid A in oat; and L-methionine -> 2[prime]-deoxymugineic acid -> mugineic acid 
      > 3-epihydroxymugineic acid in barley and beer barley.

PMID- 12231829
TI  - Metabolism and Biological Activity of Gibberellin A4 in Vegetative Shoots of Zea
      mays, Oryza sativa, and Arabidopsis thaliana.
AB  - [17-13C,3H]Gibberellin A4 (GA4) was injected into the shoots of tall (W23/L317),
      dwarf-1 (d1), and dwarf-5 (d5) Zea mays L. (maize); tall (cv Nipponbare), dwarf-x
      (dx), and dwarf-y (dy) Oryza sativa L. (rice); and tall (ecotype Landsberg
      erecta), ga4, and ga5 Arabidopsis thaliana (L.) Heynh. [13C]GA4 and its
      metabolites were identified from the shoots by full-scan gas chromatography-mass
      spectrometry and Kovats retention indices. GA4 was metabolized to GA1 in all nine
      genotypes. GA4 was also metabolized in some of the genotypes to 3-epi-GA1, GA2,
      2[beta]-OH-GA2, 3-epi-GA2, endo-GA4, 16[alpha], 17-H2-16, 17-(OH)2-GA4, GA34,
      endo-GA34, GA58, 15-epi-GA63, GA71, and 16-epi-GA82. No evidence was found for
      the metabolism of GA4 to GA7 or of GA4 to GA3. The bioactivities of GA4 and GA1
      were determined using the six dwarf mutants for assay. GA4 and GA1 had similar
      activities for the maize and rice mutants. For the Arabidopsis mutants, GA4 was
      more active than GA1 at low dosages; GA4 was less active than GA1 at higher
      dosages.

PMID- 12231830
TI  - Genetic and Physiological Analysis of a New Locus in Arabidopsis That Confers
      Resistance to 1-Aminocyclopropane-1-Carboxylic Acid and Ethylene and Specifically
      Affects the Ethylene Signal Transduction Pathway.
AB  - A population of M2 seedlings of Arabidopsis thaliana was screened for mutants
      that were insensitive to the ethylene precursor 1-aminocyclopropane-1-carboxylate
      (ACC). Several independent lines were obtained and proved insensitive to both ACC
      and ethylene. Two lines were identified as alleles of a single recessive
      mutation, designated ain1. Linkage analysis indicated that the ain1 gene is
      located on chromosome 1, adjacent to the cer5 marker and, therefore, genetically
      distinct from previously identified ethylene resistance loci. General phenotypic
      aspects of ain1 mutants were similar to wild type. For both alleles, the level of
      insensitivity to ethylene at the seedling stage was indistinguishable in terms of
      elongation growth. In contrast, the gravitropic response of ain1-1 seedlings was
      slower than that of wild-type and ain1-2 seedlings. At the adult stage, stress
      responses of mutants were similar to wild type. However, ethylene-induced leaf
      senescence was delayed in both mutants. In addition, we observed significant
      interallelic variation in ethylene production rates. Growth inhibition
      experiments showed that the ain1 mutation does not confer resistance to other
      hormones. Thus, ain1 most probably affects a step specific for the ethylene
      signal transduction pathway.

PMID- 12231831
TI  - Evidence for Two Indoleacetic Acid-Induced Growth Responses in the Avena Straight
      Growth Indoleacetic Acid Assay.
AB  - Floating Avena sativa L. cv Victory coleoptile segments were used to determine
      whether the straight-growth indoleacetic acid (IAA) assay can be reconciled with
      the Avena curvature assay and the Cholodny-Went theory of photo- and
      gravitropism. Measurements of segment length after 5 h yield sigmoid-shaped IAA
      dose-response curves with the growth rate leveling off at 1 [mu]M. However,
      measurements made at 24 h generate bell-shaped curves with maximal growth being
      induced by 10 [mu]M IAA. The difference between short- and long-term IAA dose
      response curves is not due to IAA degradation; instead, it is the result of two
      growth responses to IAA. The initial one is rapid, responds to low concentrations
      of IAA, and lasts for 12 h. The second response is less sensitive to IAA than the
      first one. It appears after 6 h but is not obvious until the last 12 h of a 24-h
      incubation. The profile of short-term IAA dose-response curves reflects the
      initial growth response, whereas that of the 24-h curve is the sum of both growth
      responses. Linear-linear plots of 5- and 24-h dose-response curves show that
      coleoptile segment growth rate is proportional to IAA concentration up to 0.3
      [mu]M. When the efficiency of IAA action is taken into account, it is found that
      the most effective IAA concentration for short and long incubations is 0.4 [mu]M.
      It is concluded that the Avena straight-growth IAA assay is as sensitive as the
      Avena coleoptile curvature assay, and that it is consistent with the Cholodny
      Went theory.

PMID- 12231832
TI  - Ethylene-Mediated Posttranscriptional Regulation in Ripening Avocado (Persea
      americana) Mesocarp Discs.
AB  - Discs of avocado (Persea americana) fruit (15 x 3 mm thick) kept in a stream of
      moist air ripen within 72 h. Following cutting, a modest evolution of wound
      ethylene that dissipates in 24 h is followed by a burst of autocatalytic ethylene
      production associated with a respiratory climacteric, much as in the intact
      fruit. Aminoethoxyvinylglycine (AVG), an inhibitor of ethylene synthesis, and 2,5
      norbornadiene (NBD) and Ag+, inhibitors of ethylene action, inhibit disc
      ripening, as does 2,4-dichlorophenoxyacetic acid (2,4-D), a synthetic auxin. On
      the other hand, none of the foregoing agents except Ag+, at concentrations that
      delay or prevent ripening, suppress the induction of four ripening-related genes
      encoding cellulase, polygalacturonase (PG), cytochrome P-450 oxidase (P-450), and
      ethylene-forming enzyme (EFE, or 1-aminopropane-1-carboxylic acid oxidase),
      respectively. Whereas Ag+ fully inhibits the production of cellulase and PG
      mRNAs, it has little effect on the induction of EFE and P-450 mRNAs. Cellulase
      and PG enzyme activities are absent in extracts of discs treated with AVG, NBD,
      or 2,4-D, as are antigenically detectable cellulase and PG proteins. The strong
      appearance of ripening-related mRNAs in discs inhibited from softening by
      ethylene antagonists suggests posttranscriptional control by ethylene. Similarly,
      inhibition of ripening by 2,4-D without suppression of mRNA induction suggests
      translational control. Whether ethylene inhibits transcription or
      postttranscriptional events or both depends on its concentration.

PMID- 12231834
TI  - Compartmentation Analysis of Paraquat Fluxes in Maize Roots as a Means of
      Estimating the Rate of Vacuolar Accumulation and Translocation to Shoots.
AB  - Efflux analysis conducted after five loading periods of various lengths (2, 6,
      12, 18, or 24 h) was used to investigate uptake, compartmentation, and
      translocation of [14C]paraquat in maize (Zea mays L.) seedlings. The time course
      for net paraquat uptake (paraquat concentration in uptake solution = 25[mu]M)
      into maize roots was linear (56.7 nmol g-1 root fresh weight h-1) for 24 h.
      Estimates of changes in paraquat content in the vacuole, cytoplasm, and cell wall
      after 2-, 6-, 12-, 18-, and 24-h loading periods indicated that the cell wall
      saturated rapidly, whereas accumulation of paraquat into the vacuole increased
      linearly (12.4 nmol g-1 root fresh weight h-1) over 24 h. In contrast to vacuolar
      accumulation, cytoplasmic paraquat content appeared to approach saturation. The
      half-time for paraquat efflux from the cell wall (16.6 min [plus or minus] 1.2
      SD) and cytoplasm (58.8 min [plus or minus] 8.9 SD remained relatively constant
      regardless of the length of the loading period, whereas the half-time for efflux
      from the vacuole was considerably longer and increased linearly with increased
      loading time (6.1-18.7 h). The time course for paraquat translocation to the
      shoot was linear within a 24-h exposure to radiolabeled herbicide, but
      translocation did not begin until 5 h after initiation of treatment. The
      experimental approach used in these experiments provides a valuable method for
      examining the movement of paraquat in maize seedlings. Results indicate that the
      herbicide slowly accumulates in the vacuole of root cells but is also
      translocated to the shoot.

PMID- 12231833
TI  - Conditioning of Parsley (Petroselinum crispum L.) Suspension Cells Increases
      Elicitor-Induced Incorporation of Cell Wall Phenolics.
AB  - The elicitor-induced incorporation of phenylpropanoid derivatives into the cell
      wall and the secretion of soluble coumarin derivatives (phytoalexins) by parsley
      (Petroselinum crispum L.) suspension cultures can be potentiated by pretreatment
      of the cultures with 2,6-dichloroisonicotinic acid or derivatives of salicylic
      acid. To investigate this phenomenon further, the cell walls and an extracellular
      soluble polymer were isolated from control cells or cells treated with an
      elicitor from Phytophthora megasperma f. sp. glycinea. After alkaline hydrolysis,
      both fractions from elicited cells showed a greatly increased content of 4
      coumaric, ferulic, and 4-hydroxybenzoic acid, as well as 4-hydroxybenzaldehyde
      and vanillin. Two minor peaks were identified as tyrosol and methoxytyrosol. The
      pretreatment effect is most pronounced at a low elicitor concentration. Its
      specificity was elaborated for coumarin secretion. When the parsley suspension
      cultures were preincubated for 1 d with 2,6-dichloroisonicotinic, 4- or 5
      chlorosalicylic, or 3,5- dichlorosalicylic acid, the cells exhibited a greatly
      increased elicitor response. Pretreatment with isonicotinic, salicylic,
      acetylsalicylic, or 2,6-dihydroxybenzoic acid was less efficient in enhancing the
      response, and some other isomers were inactive. This increase in elicitor
      response was also observed for the above-mentioned monomeric phenolics, which
      were liberated from cell walls upon alkaline hydrolysis and for "lignin-like"
      cell wall polymers determined by the thioglycolic acid method. It was shown for 5
      chlorosalicylic acid that conditioning most likely improves the signal
      transduction leading to the activation of genes encoding phenylalanine ammonia
      lyase and 4-coumarate: coenzyme A ligase. The conditioning thus sensitizes the
      parsley suspension cells to respond to lower elicitor concentrations. If a
      similar mechanism were to apply to whole plants treated with 2,6
      dichloroisonicotinic acid, a known inducer of systemic acquired resistance, one
      can hypothesize that fungal pathogens might be recognized more readily and
      effectively.

PMID- 12231835
TI  - Polyuronides in Avocado (Persea americana) and Tomato (Lycopersicon esculentum)
      Fruits Exhibit Markedly Different Patterns of Molecular Weight Downshifts during
      Ripening.
AB  - Avocado (Persea americana) fruit experience a rapid and extensive loss of
      firmness during ripening. In this study, we examined whether the chelator
      solubility and molecular weight of avocado polyuronides paralleled the
      accumulation of polygalacturonase (PG) activity and loss in fruit firmness.
      Polyuronides were derived from ethanolic precipitates of avocado mesocarp
      prepared using a procedure to rapidly inactivate endogenous enzymes. During
      ripening, chelator (cyclohexane-trans-1,2-diamine tetraacetic acid [CDTA])
      soluble polyuronides increased from approximately 30 to 40 [mu]g of galacturonic
      acid equivalents (mg alcohol-insoluble solids)-1 in preripe fruit to 150 to 170
      [mu]g mg-1 in postclimacteric fruit. In preripe fruit, chelator-extractable
      polyuronides were of high molecular weight and were partially excluded from
      Sepharose CL- 2B-300 gel filtration media. Avocado polyuronides exhibited marked
      downshifts in molecular weight during ripening. At the postclimacteric stage,
      nearly all chelator-extractable polyuronides, which constituted from 75 to 90% of
      total cell wall uronic acid content, eluted near the total volume of the
      filtration media. Rechromatography of low molecular weight polyuronides on Bio
      Gel P-4 disclosed that oligomeric uronic acids are produced in vivo during
      avocado ripening. The gel filtration behavior and pattern of depolymerization of
      avocado polyuronides were not influenced by the polyuronide extraction protocol
      (imidazole versus CDTA) or by chromatographic conditions designed to minimize
      interpolymeric aggregation. Polyuronides from ripening tomato (Lycopersicon
      esculentum) fruit extracted and chromatographed under conditions identical with
      those used for avocado polyuronides exhibited markedly less rapid and less
      extensive downshifts in molecular weight during the transition from mature-green
      to fully ripe. Even during a 9-d period beyond the fully ripe stage, tomato fruit
      polyuronides exhibited limited additional depolymerization and did not include
      oligomeric species. A comparison of the data for the avocado and tomato fruit
      indicates that downshifts in polyuronide molecular weight are a prominent feature
      of avocado ripening and may also explain why molecular down-regulation of PG (EC
      3.2.1.15) in tomato fruit has resulted in minimal effects on fruit performance
      until the terminal stages of ripening.

PMID- 12231836
TI  - Subcellular Localization of Oxygen Defense Enzymes in Soybean (Glycine max [L.]
      Merr.) Root Nodules.
AB  - Soybean (Glycine max [L.] Merr.) root nodules contain the enzymes of the
      ascorbate-glutathione pathway to minimize oxidative damage. In the present study,
      fractionation and immunocytochemistry were used to determine the subcellular
      location of the enzymes of this pathway. All four enzymes (ascorbate peroxidase,
      monodehydroascorbate reductase, dehydroascorbate reductase, and glutathione
      reductase) were present in the soluble fraction from nodule plant cells and in
      isolated mitochondria. No activity was detected in peroxisomes. Bacteroids
      contained glutathione reductase but not the other enzymes of this pathway.
      Immunogold localization indicated that ascorbate peroxidase was present in the
      cytosol of infected and uninfected cells but not in the peribacteroid space.
      Results of immunogold and immunofluorescence studies indicated that
      monodehydroascorbate reductase was located primarily in the cell wall, suggesting
      that ascorbate regeneration in the cytoplasm may proceed primarily through the
      action of dehydroascorbate reductase. The possible roles of monodehydroascorbate
      reductase in cell wall metabolism are discussed.

PMID- 12231837
TI  - Isolation and Characterization of a Chromoplast-Specific Carotenoid-Associated
      Protein from Cucumis sativus Corollas.
AB  - The differentiation of chloroplasts to chromoplasts in corollas of cucumber
      (Cucumis sativus) is subject to developmental control. To study factors involved
      in the chloroplast-chromoplast conversion, a chromoplast-specific protein of 35
      kD was isolated, and polyclonal antibodies were prepared against it. This protein
      was found to be a principal component of the carotenoid-protein complex resolved
      from chromoplast membranes by nondenaturing gel electrophoresis. Immunological
      studies revealed that expression of this protein is regulated in a temporal and
      tissue-specific manner. Its steady-state level increased in parallel with flower
      development and carotenoid accumulation, peaking in mature flowers and then
      rapidly decreasing to very low levels. The protein was not detectable in cucumber
      leaves or fruits. To ascertain whether an organ-specific system regulates the
      chloroplast-chromoplast conversion and to enable future molecular studies of
      factors involved in this regulation, an in vitro bud culture system was
      established. Patterns of expression of the 35-kD protein and carotenoids in
      corollas of detached buds were similar to those in intact buds.

PMID- 12231838
TI  - Sensitivity of Stomata to Abscisic Acid (An Effect of the Mesophyll).
AB  - The effects of added abscisic acid (ABA) on the stomatal behavior of Commelina
      communis L. were tested using three different systems. ABA was applied to
      isolated epidermis or to leaf pieces incubated in the light in bathing solutions
      perfused with CO2-free air. ABA was also fed to detached leaves in a
      transpiration bioassay. The apparent sensitivity of stomata to ABA was highly
      dependent on the method used to feed ABA. Stomata of isolated epidermis were
      apparently most sensitive to ABA, such that a concentration of 1 [mu]M caused
      almost complete stomatal closure. When pieces of whole leaves were floated on
      solutions of ABA of the same concentration, the stomata were almost completely
      open. The same concentration of ABA fed through the midrib of transpiring
      detached leaves caused an intermediate response. These differences in stomatal
      sensitivity to added ABA were found to be a function of differences in the ABA
      concentration in the epidermes. Comparison of the three application systems
      suggested that, when leaf pieces were incubated in ABA or fed with ABA through
      the midrib, accumulation of ABA in the epidermes was limited by the presence of
      the mesophyll. Even bare mesophyll incubated in ABA solution did not accumulate
      ABA. Accumulation of radioactivity by leaf pieces floated on [3H]ABA confirmed
      ABA uptake in this system. Experiments with tetcyclacis, an inhibitor of phaseic
      acid formation, suggested that rapid metabolism of ABA in mesophyll can have a
      controlling influence on ABA concentration in both the mesophyll and the
      epidermis. Inhibition of ABA catabolism with tetcyclacis allows ABA accumulation
      and increases the apparent sensitivity of stomata to applied ABA. The results are
      discussed in the context of an important role for ABA metabolism in the
      regulation of stomatal behavior.

PMID- 12231839
TI  - Effect of Jasmonic Acid on the Interaction of Barley (Hordeum vulgare L.) with
      the Powdery Mildew Erysiphe graminis f.sp. hordei.
AB  - Jasmonic acid or its methyl ester induce de novo synthesis of a number of
      proteins of mostly unknown function in barley (Hordeum vulgare L.). In a topical
      spray application, 30 [mu]g of jasmonic acid per plant effectively protected
      barley against subsequent infection by Erysiphe graminis f.sp. hordei.
      Examination of jasmonic acid-induced barley proteins revealed the presence of
      several acid-soluble (pH 2.8) proteins. Two prominent groups of 25 kD and 10 to
      12 kD apparent molecular mass were present in the intercellular washing fluid.
      The set of extracellular, induced proteins showed no similarity to barley
      pathogenesis-related proteins. An in vivo test against E. graminis revealed no
      antifungal activity of the extracellular jasmonic acid-induced proteins.
      Experiments with the transcription inhibitor cordycepin showed no correlation
      between accumulation of jasmonic acid-induced proteins and protection. The
      application of jasmonic acid and E. graminis simultaneously resulted in
      independent extracellular accumulation of both jasmonic acid-induced proteins and
      of pathogenesis-related proteins. The data suggest that jasmonic acid directly
      inhibits appressoria differentiation of the fungus, and that it is not involved
      in the signal transduction mechanism leading to induction of pathogenesis-related
      proteins.

PMID- 12231840
TI  - Further Characterization of Expression of Auxin-Induced Genes in Tobacco
      (Nicotiana tabacum) Cell-Suspension Cultures.
AB  - We have described the modulation of four auxin-regulated genes during the growth
      cycle of suspension-cultured tobacco (Nicotiana tabacum [L.] var White Burley)
      cells. The genes were transiently expressed 2 to 8 h after transfer of stationary
      phase cells to fresh medium, during the transition from the quiescent phase of
      cells leaving the mitotic cycle to the synthesis phase of the cell cycle. After
      this transient induction, the cells showed a decreased sensitivity to auxin.
      Although the expression pattern suggests that induction of these genes might be
      important for cell division, over-production of antisense mRNA for one of these
      genes (pCNT103) did not influence cell division in transgenic tobacco cells.
      Furthermore, stimuli such as salicylic acid were capable of inducing gene
      expression but were unable to restore cell division. Although these data do not
      conclusively exclude a role for these genes in cell division, their significance
      in this process is discussed in view of their homology with other auxin-induced
      genes and in view of the specificity of hormone-induced early responses.

PMID- 12231841
TI  - Identification of Catabolites of Chlorophyll-Porphyrin in Senescent Rape
      Cotyledons.
AB  - Developing shoots of rape seedlings (Brassica napus L.) were excised and fed with
      4-[14C]5-aminolevulinic acid to label the pyrroles in chlorophyll (Chl)
      synthesized during the final phase of expansion and greening of the cotyledons.
      About 80% of 14C taken up into the cotyledons was incorporated into Chl. The
      subsequent incubation of labeled shoots in permanent darkness caused the rapid
      loss of labeled Chl while increasing proportions of 14C appeared in the fraction
      of water-soluble compounds. Reversed-phase high performance liquid chromatography
      resolved three nonfluorescent polar catabolites of Chl-porphyrin that were
      progressively accumulated as senescence advanced. At intermediate stages of
      senescence, the cotyledons contained a fluorescent radio-active derivative of Chl
      that was also detectable, together with traces of other putative fluorescent
      catabolites, in isolated senescent chloroplasts. The nonfluorescent catabolites,
      identified by means of radiolabeling, were also found to accumulate in attached
      cotyledons senescing under photoperiod; under these conditions, one of the
      compounds, NCC-1, was particularly abundant. The catabolites of rape exhibited
      the same ultraviolet spectra, characterized by a maximum at 320 nm, as a
      previously reported secoporphinoid catabolite from barley (B. Krautler, B. Jaun,
      W. Amrein, K. Bortlik, M. Schellenberg, P. Matile [1992] Plant Physiol Biochem
      30: 333-346). Different polarities suggest, however, that the structures may be
      different. A terminology for Chl catabolites is proposed because present
      knowledge suggests that a large number of different structures results from
      species-specific processing of breakdown products and may require a suitable
      nomenclature.

PMID- 12231842
TI  - The Extraction and Assay of 1-Kestose:Sucrose Fructosyl Transferase from Leaves
      of Wheat.
AB  - Isolating the enzymes responsible for fructan synthesis in plants has been
      hampered by unsuitable assays used during purification. It is believed that there
      are two enzymes necessary for fructan synthesis in higher plants, one initiating
      synthesis utilizing sucrose as donor and the other elaborating the polymer using
      fructan oligomers as donor. In this paper, a rapid quantitative assay is
      described to measure the latter fructosyl transfer. The activity was absent from
      leaves that were not synthesizing fructan. Activity in crude extracts showed a
      hyperbolic dependence upon sucrose concentration. Activity against 1-kestose
      showed a pronounced optimum, suggesting that self-transfer also occurred.

PMID- 12231843
TI  - Thermoinductive Regulation of Gibberellin Metabolism in Thlaspi arvense L. (II.
      Cold Induction of Enzymes in Gibberellin Biosynthesis).
AB  - Vernalization of Thlaspi arvense L. results in the alteration of gibberellin (GA)
      metabolism such that the metabolism and turnover of the GA precursor ent-kaur-16
      en-19-oic acid (kaurenoic acid) is dramatically increased. This cold-induced
      change in GA metabolism is restricted to the shoot tip, the site of perception of
      cold in this species (J.P. Hazebroek, J.D. Metzger [1990] Plant Physiol 94: 157
      165). In the present report additional biochemical information about the nature
      of this low-temperature-regulated process is provided. The endogenous levels of
      kaurenoic acid in leaves and shoot tips of plants were estimated by combined gas
      chromatography-chemical ionization mass spectrometry at various times after 4
      weeks of vernalization at 6[deg]C. The endogenous levels in shoot tips declined
      10-fold by 2 d after the plants were returned to 21[deg]C; this decline continued
      such that there was nearly 50-fold less kaurenoic acid by 10 d after the end of
      vernalization. No effect of vernalization on the endogenous levels of kaurenoic
      acid in leaves was observed. An in vitro enzyme assay was developed to monitor
      changes in the ability of tissues to convert kaurenoic acid to ent-7[alpha]
      hydroxykaur-16-en-19-oic acid (7-OH kaurenoic acid). The activity of this enzyme
      rapidly increased in microsomal extracts from shoot tips following the end of
      vernalization. No thermoinduced increase in activity was observed in leaves. The
      enzymic oxidation of ent-kaurene to ent-kaurenol was also induced in shoot tips
      by vernalization. However, this reaction does not appear to be rate limiting for
      GA biosynthesis, because substantial amounts of kaurenoic acid accumulated in
      noninduced shoot tips. These results corroborate our hypothesis that the
      conversion of kaurenoic acid to 7-OH kaurenoic acid is the primary step in GA
      metabolism regulated by vernalization in Thlaspi shoot tips.

PMID- 12231844
TI  - Investigation of the Calcium-Transporting ATPases at the Endoplasmic Reticulum
      and Plasma Membrane of Red Beet (Beta vulgaris).
AB  - Calcium-transporting ATPases were compared in endoplasmic reticulum (ER)- and
      plasma membrane-enriched fractions of red beet (Beta vulgaris L.) storage tissue
      by measuring 45Ca uptake and calcium-dependent phosphoenzyme formation. The
      plasma membrane fraction was prepared by aqueous two-phase partitioning of a
      microsomal fraction and collecting the upper phase. The ER-enriched fraction was
      obtained by submitting a sucrose-gradient ER-enriched fraction to aqueous two
      phase partitioning and collecting the lower phase; this reduced contaminating
      plasma membrane, which partitioned into the upper phase. The ATP-dependent
      calcium uptake observed in both fractions was released by the calcium ionophore
      A23187. Calcium uptake showed saturation kinetics for calcium with Km values of
      0.92 mmol m-3 for the ER fraction and 1.24 mmol m-3 for the plasma membrane
      fraction. Uptake into both fractions was inhibited by vanadate and erythrosin B,
      although the plasma membrane system was slightly more sensitive to both
      inhibitors. Cyclopiazonic acid and thapsigargin, at low concentrations, had no
      marked effect on uptake. The plasma membrane system was less substrate-specific
      for ATP than the ER system, since it was able to use GTP and ITP to drive calcium
      transport at up to 50% of the level obtained with ATP. Following phosphorylation
      with [[gamma]-32P]ATP, two high molecular mass, calcium-dependent phosphoproteins
      (119 and 124 kD) and a low molecular mass, calcium-independent phosphoprotein (17
      kD) were observed in the plasma membrane fraction. The ER fraction showed one
      high molecular mass phosphoprotein (119 kD) in the presence of calcium and two
      low molecular mass phosphoproteins (17 and 20 kD) that showed no calcium
      dependence. The low molecular mass phosphoproteins were insensitive to hydroxyl
      amine, but they did show turnover. The identity of these proteins is unknown, but
      they do not have the properties of phosphorylated intermediates of calcium
      ATPases. In contrast, the high molecular mass phosphoproteins displayed
      properties consistent with their representing phosphorylated intermediates of
      E1E2-type ATPases; they were hydroxylamine-sensitive, showed rapid turnover, and
      were inhibited by vanadate. Because they showed calcium-dependent phosphorylation
      and were sensitive to erythrosin B, the 119- and 124-kD phosphoproteins may be
      phosphorylated intermediates of the ER and plasma membrane calcium ATPases. These
      phosphoproteins were characterized further with respect to inhibitor sensitivity,
      responses to ions, and substrate specificity.

PMID- 12231845
TI  - Developmental Profile of Diacylglycerol Acyltransferase in Maturing Seeds of
      Oilseed Rape and Safflower and Microspore-Derived Cultures of Oilseed Rape.
AB  - Diacylglycerol acyltransferase (EC 2.3.1.20) activity was assayed during the
      maturation of seeds of oilseed rape (Brassica napus L.) and safflower (Carthamus
      tinctorius L.). Developmental studies were also conducted with microspore-derived
      embryos of oilseed rape (B. napus L. cv Topas) and an embryogenic microspore
      derived cell-suspension culture of winter oilseed rape (B. napus L. cv Jet Neuf).
      In the maturing seeds, diacylglycerol acyltransferase activity increased to a
      maximum during rapid accumulation of lipid and declined, thereafter, with seed
      maturity. In microspore-derived embryos of oilseed rape (cv Topas), high levels
      of diacylglycerol acyltransferase activity were found throughout the early
      torpedo to late cotyledonary developmental stages with maximum enzyme specific
      activity associated with the mid-cotyledonary developmental stage. The cell
      suspension culture of winter oilseed rape (cv Jet Neuf) contained 3 to 4%
      triacylglycerol on a dry weight basis and represented about half of the total
      lipid. The fatty acid profile of total lipid and triacylglycerol in the cell
      suspension culture was similar in samples taken during a 1-year period. The Jet
      Neuf culture contained diacylglycerol acyltransferase with specific activity
      similar to that of Topas microspore-derived embryos. Jet Neuf diacylglycerol
      acyltransferase also displayed an enhanced specificity for erucoyl-CoA over
      oleoyl-CoA when assayed with 14 [mu]M acyl-coenzyme A in the reaction mixture.
      The specific activity of diacylglycerol acyltransferase in homogenates prepared
      from the Jet Neuf culture ranged from 5 to 15 pmol of triacylglycerol min-1 mg-1
      of protein when assayed at intervals during a period of 1 year. Thus, the cell
      suspension culture may represent an attractive tissue source for purification and
      characterization of triacyl-glycerol biosynthetic enzymes.

PMID- 12231846
TI  - The Use of Fura-2 Fluorescence to Monitor the Movement of Free Calcium Ions into
      the Matrix of Plant Mitochondria (Pisum sativum and Helianthus tuberosus).
AB  - Purified mitochondria isolated from pea (Pisum sativum L. cv Alaska) stems and
      Jerusalem artichoke (Helianthus tuberosus L. cv OB1) tubers were loaded with the
      acetoxymethyl ester of the fluorescent Ca2+ indicator fura-2. This made possible
      the continuous monitoring of free [Ca2+] in the matrix ([Ca2+]m) without
      affecting the apparent viability of the mitochondria. Pea stem mitochondria
      contained an initial [Ca2+]m of approximately 60 to 100 nM, whereas [Ca2+]m was
      severalfold higher (400-600 nM) in mitochondria of Jerusalem artichoke tubers. At
      low extramitochondrial Ca2+ concentrations ([greater than or equal to]100 nM),
      there was an energy-dependent membrane potential increase in [Ca2+]m; the final
      [Ca2+]m was phosphate-dependent in Jerusalem artichoke but was phosphate
      independent in pea stem mitochondria. The data presented indicate that (a) there
      is no absolute requirement for phosphate in Ca2+ uptake; (b) plant mitochondria
      can accumulate external free Ca2+ by means of an electrophoretic Ca2+ uniporter
      with an apparent affinity for Ca2+ (Km approximately 150 nM) that is severalfold
      lower than that measured by conventional methods (isotopes and Ca2+-sensitive
      electrodes); and (c) [Ca2+]m is within the regulatory range of mammalian
      intramitochondrial dehydrogenases.

PMID- 12231847
TI  - Oxidation of External NAD(P)H by Mitochondria from Taproots and Tissue Cultures
      of Sugar Beet (Beta vulgaris).
AB  - The present study compares the exogenous NAD(P)H oxidation and the membrane
      potential ([delta][psi]) generated in mitochondria isolated from different
      tissues of an important agricultural crop, sugar beet (Beta vulgaris}. We
      observed that mitochondria from taproots, cold-stored taproots, and in vitro
      grown tissue cultures contain a functional NADH dehydrogenase, whereas only those
      isolated from tissue cultures displayed a functional NAD(P)H dehydrogenase. It is
      interesting that the NADH-dependent [delta][psi] of mitochondria from cold-stored
      taproots and from tissue cultures was not affected by free Ca2+ ions, whereas
      free Ca2+ was required for the mitochondrial NADPH oxidation by in vitro-grown
      cells and cytosolic NADH oxidation by mitochondria from fresh taproots. A
      tentative model accounting for the different response to Ca2+ ions of the NADH
      dehydrogenase in mitochondria from cold-stored taproots and tissue cultures of B.
      vulgaris is discussed.

PMID- 12231849
TI  - NADH Oxidase Activity of Plasma Membranes of Soybean Hypocotyls Is Activated by
      Guanine Nucleotides.
AB  - The activity of an auxin-stimulated NADH oxidase of the plasma membrane of
      hypocotyls of etiolated soybean (Glycine max Merr.) seedlings responded to
      guanine and other nucleotides, but in a manner that differed from that of enzymes
      coupled to the classic trimeric and low molecular weight monomeric guanine
      nucleotide-binding proteins (G proteins). In the presence and absence of either
      auxin or divalent ions, both GTP and GDP as well as guanosine-5[prime]-O-(3
      thiotriphosphate) (GTP-[gamma]-S) and other nucleoside di- and triphosphates
      stimulated the oxidase activity over the range 10 [mu]M to 1 mM. GTP and GTP
      [gamma]-S stimulated the activity at 10 nM in the absence of added magnesium and
      at 1 nM in the presence of added magnesium ions. Other nucleotides stimulated at
      100 nM and above. The NADH oxidase was stimulated by 10 [mu]M mastoparan and by
      40 [mu]M aluminum fluoride. Neither cholera nor pertussis toxins, tested at a
      concentration sufficient to block mammalian G protein function, inhibited the
      activity. Guanosine 5[prime]-O-(2-thiodi-phosphate) (GDP-[beta]-S) did not
      stimulate activity, suggesting that the stimulation in response to GDP may be
      mediated by a plasma membrane nucleoside diphosphate kinase through conversion of
      GDP to GTP. Auxin stimulation of the NADH oxidase was unaffected by nucleotides
      at either high or low nucleotide concentrations in the absence of added divalent
      ions. However, pretreatment of plasma membranes with auxin increased the apparent
      affinity for nucleotide binding. This increased affinity, however, appeared not
      to be the mechanism of auxin stimulation of the oxidase, since auxin stimulation
      was similar with or without low concentrations of guanine nucleotides. The
      stimulation by nucleotides was observed after incubating the membranes with 0.1%
      Triton X-100 prior to assay. The results suggest a role of guanine (and other)
      nucleotides in the regulation of plasma membrane NADH oxidase that differs from
      the interactions with G proteins commonly described for animal models.

PMID- 12231848
TI  - Respiration of Sugars in Spinach (Spinacia oleracea), Maize (Zea mays), and
      Chlamydomonas reinhardtii F-60 Chloroplasts with Emphasis on the Hexose Kinases.
AB  - The role of hexokinase in carbohydrate degradation in isolated, intact
      chloroplasts was evaluated. This was accomplished by monitoring the evolution of
      14CO2 from darkened spinach (Spinacia oleracea), maize (Zea mays) mesophyll, and
      Chlamydomonas reinhardtii chloroplasts externally supplied with 14C-labeled
      fructose, glucose, mannose, galactose, maltose, and ribose. Glucose and ribose
      were the preferred substrates with the Chlamydomonas and maize chloroplasts,
      respectively. The rate of CO2 release from fructose was about twice that from
      glucose in the spinach chloroplast. Externally supplied ATP stimulated the rate
      of CO2 release. The pH optimum for CO2 release was 7.5 with ribose and fructose
      and 8.5 with glucose as substrates. Probing the outer membrane polypeptides of
      the intact spinach chloroplast with two proteases, trypsin and thermolysin,
      decreased 14CO2 release from glucose about 50% but had little effect when
      fructose was the substrate. Tryptic digestion decreased CO2 release from glucose
      in the Chlamydomonas chloroplast about 70%. 14CO2 evolution from [1-14C]-glucose
      6-phosphate in both chloroplasts was unaffected by treatment with trypsin.
      Enzymic analysis of the supernatant (stroma) of the lysed spinach chloroplast
      indicated a hexokinase active primarily with fructose but with some affinity for
      glucose. The pellet (membranal fraction) contained a hexokinase utilizing both
      glucose and fructose but with considerably less total activity than the stromal
      enzyme. Treatment with trypsin and thermolysin eliminated more than 50% of the
      glucokinase activity but had little effect on fructokinase activity in the
      spinach chloroplast. Tryptic digestion of the Chlamydomonas chloroplast resulted
      in a loss of about 90% of glucokinase activity.

PMID- 12231850
TI  - Distribution of Gibberellins in Lathyrus odoratus L. and Their Role in Leaf
      Growth.
AB  - In sweet pea (Lathyrus odoratus L.) the mutant allele l reduced the level of
      gibberellin A1 (GA1) in expanding leaflets and resulted in smaller, more oval
      leaflets compared with the wild type. The apical portions of 6-d-old wild-type
      (L) seedlings also contained less GA1 and produced smaller, more oval leaflets
      than did comparable 20-d-old L seedlings. Application of GA1 markedly altered
      leaflet shape and, at certain dosages, restored the wild-type shape and size to
      leaflets of the l (dwarf) mutant. Taken together, these observations indicate
      that GA1 performs a regulatory role in the control of leaf growth in this
      species. The levels of GA1 precursors in the wild type were also determined.
      Rapidly expanding internodes contained much more gibberellin A19 (GA19) than
      gibberellin A20 (GA20), whereas the opposite was true for expanding leaflets.
      Although in entire apical portions of established seedlings the level of GA20
      exceeded that of GA19, apical portions of very young seedlings contained more
      GA19 than GA20. Basal stem tissue of established seedlings also contained
      substantially more GA19 than GA20 or GA1. Both stems and leaflets from the basal
      portion of the plant contained much less GA20 and GA1 than did the rapidly
      expanding apical tissue. The implications of these results for the regulation of
      GA1 biosynthesis are discussed.

PMID- 12231851
TI  - Synthesis of Benzylglucosinolate in Tropaeolum majus L. (Isothiocyanates as
      Potent Enzyme Inhibitors).
AB  - Benzylglucosinolate accumulates in mature plants of Tropaeolum majus L. The
      biosynthetic capacity for synthesis of benzylglucosinolate and the total content
      of benzylglucosinolate have been investigated during plant development and in
      different tissues. The content increased from 5 mg of benzylglucosinolate in the
      fresh seed to between 200 and 400 mg in the adult plant, depending on size. The
      biosynthetic capacity was measured using L-[U-14C]phenylalanine as precursor.
      Incorporation levels of approximately 30% were obtained with green leaves,
      whereas the incorporation levels obtained with other tissues were in the range of
      0 to 5%. Leaves were the primary site of benzylglucosinolate synthesis. The high
      amounts of benzylglucosinolate accumulated in other tissues (e.g. developing
      seeds) reflected transport of benzylglucosinolate from the leaves. The initial
      steps in the biosynthesis of glucosinolates and cyanogenic glycosides are thought
      to be similar and to be localized on microsomal membranes. However, a microsomal
      system prepared from T. majus was biosynthetically inactive. Inclusion of T.
      majus plant material during preparation of sorghum microsomes also inhibited
      their activity. Benzylisothiocyanate, generated by degradation of
      benzylglucosinolate during the homogenization procedure, strongly inhibited the
      sorghum enzyme system, and its presence may thus explain why the isolated T.
      majus microsomal system is inactive.

PMID- 12231852
TI  - Purification and Characterization of Porin from Corn (Zea mays L.) Mitochondria.
AB  - Mitochondrial porin from corn (Zea mays L. B 73) shoots was solubilized with
      lauryl(dimethyl)-amine oxide and purified by chromatography on a
      hydroxyapatite:celite column. On sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, the purified protein had an apparent molecular mass of 35 kD.
      When reconstituted in planar lipid bilayer membranes the porin formed ion
      permeable channels with single-channel conductance of 2.0 and 4.0 nanosiemens in
      1 M KCl. At low transmembrane voltages corn porin had the properties of a general
      diffusion pore with an estimated effective diameter of 1.6 nm and a small
      selectivity for anions over cations. The primary structure of corn porin seems to
      be quite different from that of other mitochondrial porins, because it did not
      cross-react with monoclonal antibodies against human porin and with polyclonal
      antibodies against yeast porin. Furthermore, the peptide maps of corn and bovine
      heart porins were very different. A sequence of 21 amino acids obtained by Edman
      degradation of peptides generated by porin proteolysis with Staphylococcus aureus
      V8 protease did not show any significant homology with known sequences of
      mitochondrial porins. Results of our investigation suggest that corn porin
      possesses functional properties similar to those of other mitochondrial porins,
      despite major structural differences.

PMID- 12231853
TI  - An in Vivo Nuclear Magnetic Resonance Investigation of Ion Transport in Maize
      (Zea mays) and Spartina anglica Roots during Exposure to High Salt
      Concentrations.
AB  - The response of maize (Zea mays L.) and Spartina anglica root tips to exposure to
      sodium chloride concentrations in the range 0 to 500 mM was investigated using
      23Na and 31P nuclear magnetic resonance spectroscopy (NMR). Changes in the
      chemical shift of the pH-dependent 31P-NMR signals from the cytoplasmic and
      vacuolar orthophosphate pools were correlated with the uptake of sodium, and
      after allowing for a number of complicating factors we concluded that these
      chemical shift changes indicated the occurrence of a small cytoplasmic
      alkalinization (0.1-0.2 pH units) and a larger vacuolar alkalinization (0.6 pH
      units) in maize root tips exposed to salt concentrations greater than 200 mM. The
      data were interpreted in terms of the ion transport processes that may be
      important during salt stress, and we concluded that the vacuolar alkalinization
      provided evidence for the operation of a tonoplast Na+/H+-antiport with an
      activity that exceeded the activity of the tonoplast H+ pumps. The intracellular
      pH values stabilized during prolonged treatment with high salt concentrations,
      and this observation was linked to the recent demonstration (Y. Nakamura, K.
      Kasamo, N. Shimosato, M. Sakata, E. Ohta [1992] Plant Cell Physiol 33: 139-149)
      of the salt-induced activation of the tonoplast H+- ATPase. Sodium vanadate, an
      inhibitor of the plasmalemma H+- ATPase, stimulated the net uptake of sodium by
      maize root tips, and this was interpreted in terms of a reduction in active
      sodium efflux from the tissue. S. anglica root tips accumulated sodium more
      slowly than did maize, with no change in cytoplasmic pH and a relatively small
      change (0.3 pH units) in vacuolar pH, and it appears that salt tolerance in
      Spartina is based in part on its ability to prevent the net influx of sodium
      chloride.

PMID- 12231854
TI  - A Novel Fungal Protease Expressed in Endophytic Infection of Poa Species.
AB  - The fungus Acremonium typhinum produces a novel endoprotease during symbiotic
      endophytic infection of the grass, Poa ampla. This protease is unusual because it
      is highly active in the presence of sodium dodecyl sulfate. The enzyme is a thiol
      containing serine protease and is localized to a crude membrane fraction. Similar
      protease activity has been detected in endophyte-infected Poa autumnalis and Poa
      sylvestris plants. Expression of this protease may be important in endophytic
      infection of Poa spp., because similar activity has not been detected in
      endophyte-infected Festuca arundinacea or Lolium perenne.

PMID- 12231856
TI  - Pigmented Soybean (Glycine max) Seed Coats Accumulate Proanthocyanidins during
      Development.
AB  - The dominant I gene inhibits accumulation of anthocyanin pigments in the
      epidermal layer of soybean (Glycine max) seed coats. Seed-coat color is also
      influenced by the R locus and by the pubescence color alleles (T, tawny; t,
      gray). Protein and RNA from cultivars with black (i,R,T) and brown (i,r,T) seed
      coats are difficult to extract. To determine the nature of the interfering plant
      products, we examined seed-coat extracts from Clark isogenic lines for
      flavonoids, anthocyanins, and possible proanthocyanidins by thin-layer
      chromatography. We show that yellow seed-coat varieties (I) do not accumulate
      anthocyanins (anthocyanidin glycosides) or proanthocyanidins (polymeric
      anthocyanidins). Mature, black (i,R,T) and imperfect-black (i,R,t) seed coats
      contained anthocyanins, whereas mature, brown (i,r,T) and buff (i,r,t) seed coats
      did not contain anthocyanins. In contrast, all colored (i) genotypes tested
      positive for the presence of proanthocyanidins by butanol/ HCl and 0.5% vanillin
      assays. Immature, black (i,R,T) and brown (i,r,T) seed coats contained
      significant amounts of procyanidin, a 3[prime],4[prime]-hydroxylated
      proanthocyanidin. Immature, black (i,R,T) or brown (i,r,T) seed-coat extracts
      also tested positive for the ability to precipitate proteins in a radial
      diffusion assay and to bind RNA in vitro. Imperfect-black (i,R,t) or buff (i,r,t)
      seed coats contained lesser amounts of propelargonidin, a 4[prime]-hydroxylated
      proanthocyanidin. Seed-coat extracts from these genotypes did not have the
      ability to precipitate protein or bind to RNA. In summary, the dominant I gene
      controls inhibition of not only anthocyanins but also proanthocyanidins in
      soybean seed coats. In homozygous recessive i genotypes, the T-t gene pair
      determines the types of proanthocyanidins present, which is consistent with the
      hypothesis that the T locus encodes a microsomal 3[prime]-flavonoid hydroxylase.

PMID- 12231855
TI  - A Plasma Membrane-Type Ca2+-ATPase of 120 Kilodaltons on the Endoplasmic
      Reticulum from Carrot (Daucus carota) Cells (Properties of the Phosphorylated
      Intermediate).
AB  - Cytosolic Ca2+ levels are regulated in part by Ca2+-pumping ATPases that export
      Ca2+ from the cytoplasm; however, the types and properties of Ca2+ pumps in
      plants are not well understood. We have characterized the kinetic properties of a
      120-kD phosphoenzyme (PE) intermediate formed during the reaction cycle of a Ca2+
      ATPase from suspension-cultured carrot (Daucus carota) cells. Only one Ca2+
      dependent phosphoprotein was formed when carrot membrane vesicles were incubated
      with [[gamma]-32P]ATP (W.L. Hsieh, W.S. Pierce, and H. Sze [1991] Plant Physiol
      97: 1535-1544). Formation of this 120-kD phosphoprotein was inhibited by
      vanadate, enhanced by La3+, and decreased by hydroxylamine, confirming its
      identification as an intermediate of a phosphorylated-type Ca2+-translocating
      ATPase. The 120-kD Ca2+-ATPase was most abundant in endoplasmic reticulum
      enriched fractions, in which the Ca2+-ATPase was estimated to be 0.1% of membrane
      protein. Direct quantitation of Ca2+-dependent phosphoprotein was used to examine
      the kinetics of PE formation. PE formation exhibited a Km for Ca2+ of 1 to 2
      [mu]M and a Km for ATP of 67 nM. Relative affinities of substrates, determined by
      competition experiments, were 0.075 [mu]M for ATP, 1 [mu]M for ADP, 100 [mu]M for
      ITP, and 250 [mu]M for GTP. Thapsigargin and cyclopiazonic acid, specific
      inhibitors of animal sarcoplasmic/endoplasmic reticulum Ca2+-ATPase, had no
      effect on PE formation; erythrosin B inhibited with 50% inhibition at <0.1 [mu]M.
      Calmodulin (1 [mu]M) stimulated PE formation by 25%. The results indicate that
      the carrot 120-kD Ca2+-ATPase is similar but not identical to animal plasma
      membrane-type Ca2+- ATPase and yet is located on endomembranes, such as the
      endoplasmic reticulum. This type of Ca2+ pump may reside on the cortical
      endoplasmic reticulum, which is thought to play a major role in anchoring the
      cytoskeleton and in facilitating secretion.

PMID- 12231857
TI  - Specificity and Photomorphogenic Nature of Ultraviolet-B-Induced Cotyledon
      Curling in Brassica napus L.
AB  - Three general classes of photomorphogenic photoreceptors have been characterized
      in higher plants: phytochrome, a blue light/ultraviolet (UV)-A photoreceptor(s),
      and a UV-B sensory system(s). Although a great deal is known about phytochrome
      and the blue light/UV-A photoreceptor(s), little is known about UV-B detection
      processes. One reason for this is the lack of readily quantifiable morphogenic
      responses that are specifically induced by UV-B radiation. We have discovered a
      response to UV-B, upward curling of Brassica napus L. cotyledons, that may be
      useful for probing the mechanism of UV-B photoreception. The process was
      initially observed when B. napus seeds were germinated under visible light plus
      UV-B radiation, but did not occur under visible light alone or visible light plus
      UV-A. When 5-d-old seedlings grown in visible light were given relatively short
      exposures of UV-B (100 min of 5.5 [mu]mol m-2 s-1), the curling response was also
      observed. Development of curling was separated from the application of this UV-B
      pulse by a 14-h latent period. Pulses of red light, blue light, farred light, and
      UV-A (100 min of 5.5 [mu]mol m-2 s-1) did not induce curling, indicating UV-B
      specificity Additionally, these other spectral regions did not reverse or enhance
      the UV-B-triggered response. The degree of curling showed a log-linear dependence
      on UV-B fluence (6-40 mmol m-2) and reciprocity with respect to length of
      exposure and fluence rate. The data indicate that curling is photomorphogenic in
      nature and may be triggered by a single photoreceptor species.

PMID- 12231858
TI  - Plant Phosphoinositides and Intracellular Signaling.

PMID- 12231859
TI  - The Guard Cell-Environment Connection.

PMID- 12231860
TI  - Magnitude and Kinetics of Stem Elongation Induced by Exogenous Indole-3-Acetic
      Acid in Intact Light-Grown Pea Seedlings.
AB  - Exogenously applied indole-3-acetic acid (IAA) strongly promoted stem elongation
      over the long term in intact light-grown seedlings of both dwarf (cv Progress No.
      9) and tall (cv Alaska) peas (Pisum sativum L.), with the relative promotion
      being far greater in dwarf plants. In dwarf seedlings, solutions of IAA (between
      10-4 and 10-3 M), when continuously applied to the uppermost two internodes via a
      cotton wick, increased whole-stem growth by at least 6-fold over the first 24 h.
      The magnitude of growth promotion correlated with the applied IAA concentration
      from 10-6 to 10-3 M, particularly over the first 6 h of application. IAA applied
      only to the apical bud or the uppermost internode of the seedling stimulated a
      biphasic growth response in the uppermost internode and the immediately lower
      internode, with the response in the latter being greatly delayed. This
      demonstrates that exogenous IAA effectively promotes growth as it is transported
      through intact stems. IAA withdrawal and reapplication at various times enabled
      the separation of the initial growth response (IGR) and prolonged growth response
      (PGR) induced by auxin. The IGR was inducible by at least 1 order of magnitude
      lower IAA concentrations than the PGR, suggesting that the process underlying the
      IGR is more sensitive to auxin induction. In contrast to the magnitude of the IAA
      effect in dwarf seedlings, applied IAA only doubled the growth in tall seedlings.
      These results suggest that endogenous IAA is more growth limiting in dwarf plants
      than in tall plants, and that auxin promotes stem elongation in the intact plant
      probably by the same mechanism of action as in isolated stem segments. However,
      since dwarf plants to which IAA was applied failed to reach the growth rate of
      tall plants, auxin cannot be the only limiting factor for stem growth in peas.

PMID- 12231861
TI  - Rapid and Reversible High-Affinity Binding of the Dinitroaniline Herbicide
      Oryzalin to Tubulin from Zea mays L.
AB  - Oryzalin, a dinitroaniline herbicide, was previously reported to bind to plant
      tubulin with a moderate strengthe interaction (dissociation constant [Kd] = 8.4
      [mu]M) that appeared inconsistent with the nanomolar concentrations of drug that
      cause the loss of microtubules, inhibit mitosis, and produce herbicidal effects
      in plants (L.C. Morejohn, T.E. Bureau, J. Mole-Bajer, A.S. Bajer, D.E. Fosket
      [1987] Planta 172: 252-264). To characterize further the mechanism of action of
      oryzalin, both kinetic and quasi-equilibrium ligand-binding methods were used to
      examine the interaction of [14C]-oryzalin with tubulin from cultured cells of
      maize (Zea mays L. cv Black Mexican Sweet). Oryzalin binds to maize tubulin dimer
      via a rapid and pH-dependent interaction to form a tubulin-oryzalin complex. Both
      the tubulin-oryzalin binding strength and stoichiometry are underestimated
      substantially when measured by kinetic binding methods, because the tubulin
      oryzalin complex dissociates rapidly into unliganded tubulin and free oryzalin.
      Also, an uncharacterized factor(s) that is co-isolated with maize tubulin was
      found to noncompetitively inhibit oryzalin binding to the dimer. Quasi
      equilibrium binding measurements of the tubulin-oryzalin complex using purified
      maize dimer afforded a Kd of 95 nM (pH 6.9; 23[deg]C) and an estimated maximum
      molar binding stoichiometry of 0.5. No binding of oryzalin to pure bovine brain
      tubulin was detected by equilibrium dialysis, and oryzalin has no discernible
      effect on microtubules in mouse 3T3 fibroblasts, indicating an absence of the
      oryzalin-binding site on mammalian tubulin. Oryzalin binds to pure taxol
      stabilized maize microtubules in a polymer mass- and number-dependent manner,
      although polymerized tubulin has a much lower oryzalin-binding capacity than
      unpolymerized tubulin. Much more oryzalin is incorporated into polyment during
      taxol-induced assembly of pure maize tubulin, and half-maximal inhibition of the
      rapid phase of taxol-induced polymerization of 5 [mu]M tubulin is obtained with
      700 [mu]M oryzalin. The data are consistent with a molecular mechanism whereby
      oryzalin binds rapidly, reversibly, and with high affinity to the plant tubulin
      dimer to form a tubulin-oryzalin complex that, at concentrations
      substoichiometric to tubulin, copolymerizes with unliganded tubulin and slows
      further assembly. Because half-maximal inhibition of maize callus growth is
      produced by 37 nM oryzalin, the herbicidal effects of oryzalin appear to result
      from a substoichiometric poisoning of microtubules.

PMID- 12231862
TI  - Induction of Nonphotochemical Energy Dissipation and Absorbance Changes in Leaves
      (Evidence for Changes in the State of the Light-Harvesting System of Photosystem
      II in Vivo).
AB  - Simultaneous measurements of nonphotochemical quenching of chlorophyll
      fluorescence and absorbance changes in the 400- to 560-nm region have been made
      following illumination of dark-adapted leaves of the epiphytic bromeliad Guzmania
      monostachia. During the first illumination, an absorbance change at 505 nm
      occurred with a half-time of 45 s as the leaf zeaxanthin content rose to 14% of
      total leaf carotenoid. Selective light scattering at 535 nm occurred with a half
      time of 30 s. During a second illumination, following a 5-min dark period,
      quenching and the 535-nm absorbance change occurred more rapidly, reaching a
      maximum extent within 30 s. Nonphotochemical quenching of chlorophyll
      fluorescence was found to be linearly correlated to the 535-nm absorbance change
      throughout. Examination of the spectra of chlorophyll fluorescence emission at 77
      K for leaves sampled at intervals during this regime showed selective quenching
      in the light-harvesting complexes of photosystem II (LHCII). The quenching
      spectrum of the reversible component of quenching had a maximum at 700 nm,
      indicating quenching in aggregated LHCII, whereas the irreversible component
      represented a quenching of 680-nm fluorescence from unaggregated LHCII. It is
      suggested that this latter process, which is associated with the 505-nm
      absorbance change and zeaxanthin formation, is indicating a change in state of
      the LHCII complexes that is necessary to amplify or activate reversible pH
      dependent energy dissipation, which is monitored by the 535-nm absorbance change.
      Both of the major forms of nonphotochemical energy dissipation in vivo are
      therefore part of the same physiological photoprotective process and both result
      from alterations in the LHCII system.

PMID- 12231863
TI  - Immunological Evidence for the Existence of a Carrier Protein for Sucrose
      Transport in Tonoplast Vesicles from Red Beet (Beta vulgaris L.) Root Storage
      Tissue.
AB  - Monoclonal antibodies were raised in mice against a highly purified tonoplast
      fraction from isolated red beet (Beta vulgaris L. ssp. conditiva) root vacuoles.
      Positive hybridoma clones and sub-clones were identified by prescreening using an
      enzyme-linked immunosorbent assay (ELISA) and by postscreening using a functional
      assay. This functional assay consisted of testing the impact of hybridoma
      supernatants and antibody-containing ascites fluids on basal and ATP-stimulated
      sugar uptake in vacuoles, isolated from protoplasts, as well as in tonoplast
      vesicles, prepared from tissue homogenates of red beet roots. Antibodies from
      four clones were particularly positive in ELISAs and they inhibited sucrose
      uptake significantly. These antibodies were specific inhibitors of sucrose
      transport, but they exhibited relatively low membrane and species specificity
      since uptake into red beet root protoplasts and sugarcane tonoplast vesicles was
      inhibited as well. Fast protein liquid chromatography assisted size exclusion
      chromatography on Superose 6 columns yielded two major peaks in the 55 to 65-kD
      regions and in the 110- to 130-kD regions of solubilized proteins from red beet
      root tonoplasts, which reacted positively in immunoglobulin-M(IgM)-specific
      ELISAs with anti-sugarcane tonoplast monoclonal IgM antibodies. Only
      reconstituted proteoliposomes containing polypeptides from the 55- to 65-kD band
      took up [14C]-sucrose with linear rates for 2 min, suggesting that this fraction
      contains the tonoplast sucrose carrier.

PMID- 12231864
TI  - Catalytic Properties of a Newly Discovered Acyltransferase That Synthesizes N
      Acylphosphatidylethanolamine in Cottonseed (Gossypium hirsutum L.) Microsomes.
AB  - We recently demonstrated that cotyledons of cotton (Gossypium hirsutum L.)
      seedlings synthesize N-acylphosphatidylethanolamine (NAPE), an unusual acylated
      derivative of phosphatidylethanolamine (PE), during postgerminative growth (K.D.
      Chapman and T.S. Moore [1993] Arch Biochem Biophys 301: 21-33). Here, we report
      the discovery of an acyltransferase enzyme, fatty acid:
      diacylphosphatidylethanolamine N-acyltransferase (designated NAPE synthase), that
      synthesizes NAPE from PE and free fatty acids (FFA) in cottonseed microsomes.
      [14C]NAPE was synthesized from [14C]palmitic acid and endogenous PE in a time-,
      pH-, temperature-, and protein concentration-dependent manner. [14C]Palmitic acid
      was incorporated exclusively into the N-acyl position of NAPE. [14C]palmitoyl
      coenzyme A (CoA) and [14C]-dipalmitoyl phosphatidylcholine (PC) were poor acyl
      donors for the synthesis of NAPE (i.e. 200- and 3000-fold lower incorporation
      efficiency than palmitic acid, respectively). Synthesis of NAPE from palmitoyl
      CoA and dipalmitoyl-PC was observed only after the release of FFA in microsomes.
      We observed a temperature optimum of 45[deg]C and a pH optimum of 8.0 for the
      synthesis of [14C]NAPE from [14C]palmitic acid (or from [14C]PE). NAPE synthase
      activity showed no apparent divalent cation requirement. Notably, activity was
      stimulated by HPO42-, HCO3-, SO42-, and NADPH, whereas activity was inhibited by
      Ca2+, Mn2+, Cd2+, ATP, ADP, flavin adenine disnucleotide, and flavin
      mononucleotide. Other nucleotide triphosphates (GTP and CTP) and pyridine
      dinucleotides (NAD, NADH, and NADP) did not appreciably affect NAPE synthase
      activity. Initial velocity measurements of NAPE synthase activity at increasing
      concentrations of palmitic acid showed non-Michaelis-Menten, biphasic kinetics. A
      high-affinity site (S0.5 = 7.2 [mu]M, Vmax = 18.8 nmol h-1 mg-1 of protein) and a
      low-affinity site (S0.5 = 32.0 [mu]M, Vmax = 44.9 nmol h-1 mg-1 of protein) were
      identified. Both sites exhibited positive cooperativity. Adding myristic,
      stearic, or oleic acids at equimolar amounts reduced the incorporation of
      [14C]palmitic acid into NAPE at low concentrations (10 [mu]M, high-affinity site)
      but not at high concentrations (50 [mu]M, low-affinity site), indicating that the
      two putative sites can be distinguished by their fatty acid preferences.

PMID- 12231865
TI  - Influence of Species of Vesicular-Arbuscular Mycorrhizal Fungi and Phosphorus
      Nutrition on Growth, Development, and Mineral Nutrition of Potato (Solanum
      tuberosum L.).
AB  - Growth, development, and mineral physiology of potato (Solanum tuberosum L.)
      plants in response to infection by three species of vesicular-arbuscular
      mycorrhizal (VAM) fungi and different levels of P nutrition were characterized. P
      deficiency in no-P and low-P (0.5 mM) nonmycorrhizal plants developed between 28
      and 84 d after planting. By 84 d after planting, P deficiency decreased plant
      relative growth rate such that no-P and low-P plants had, respectively, 65 and
      45% less dry mass and 76 and 55% less total P than plants grown with high P (2.5
      mM). A severe reduction in leaf area was also evident, because P deficiency
      induced a restriction of lateral bud growth and leaf expansion and, also,
      decreased the relative plant allocation of dry matter to leaf growth. Root growth
      was less influenced by P deficiency than either leaf or stem growth. Moreover, P
      deficient plants accumulated a higher proportion of total available P than high-P
      plants, indicating that P stress had enhanced root efficiency of P acquisition.
      Plant P deficiency did not alter the shoot concentration of N, K, Mg, or Fe;
      however, the total accumulation of these mineral nutrients in shoots of P
      stressed plants was substantially less than that of high-P plants. P uptake by
      roots was enhanced by each of the VAM symbionts by 56 d after planting and at all
      levels of abiotic P supply. Species differed in their ability to colonize roots
      and similarly to produce a plant growth response. In this regard, Glomus
      intraradices (Schenck and Smith) enhanced plant growth the most, whereas Glomus
      dimorphicum (Boyetchko and Tewari) was least effective, and Glomus mosseae
      ([Nicol. and Gerd.] Gerd. and Trappe) produced an intermediate growth response.
      The partial alleviation of P deficiency in no-P and low-P plants by VAM fungi
      stimulated uptake of N, K, Mg, Fe, and Zn. VAM fungi enhanced shoot
      concentrations of P, N, and Mg by 28 d after planting and, through a general
      improvement of overall plant mineral nutrition, promoted plant growth and
      development.

PMID- 12231866
TI  - Chromoplast-Targeted Proteins in Tomato (Lycopersicon esculentum Mill.) Fruit.
AB  - The chloroplast to chromoplast transition during tomato (Lycopersicon esculentum
      Mill.) fruit ripening is characterized by a dramatic change in plastid structure
      and function. We have asked whether this process is mediated by an increase in
      the steady-state level of RNA for plastid targeted proteins. Assays for import of
      radiolabeled translation products into isolated pea (Pisum sativum L.)
      chloroplasts were used to monitor levels of chromoplast-targeted proteins at four
      stages of tomato fruit development. We have found striking increases during
      development in levels of translatable RNA for two such proteins. Additionally,
      the import of in vitro translation products was examined for seven individual
      cDNA clones known to encode RNA that increase during fruit ripening. Three of
      these clones produced in vitro translation products that were imported into pea
      chloroplasts. This implies that there is synthesis and import of new proteins
      during the transition from chloroplast to chromoplast and that the plastid
      conversion is an active developmental program rather than a simple decline in
      synthesis of the photosynthetic apparatus. Furthermore, our results demonstrate
      the utility of this method for identification of structural genes involved in
      plastid morphogenesis.

PMID- 12231867
TI  - Partial Characterization of Glutathione S-Transferase Isozymes Induced by the
      Herbicide Safener Benoxacor in Maize.
AB  - The effects of the dichloroacetamide safener benoxacor on maize (Zea mays L. var
      Pioneer 3906) growth and glutathione S-transferase (GST) activity were evaluated,
      and GST isozymes induced by benoxacor were partially separated, characterized,
      and identified. Protection from metolachlor injury was closely correlated with
      GST activity, which was assayed with metolachlor as a substrate, as benoxacor
      concentration increased from 0.01 to 1 [mu]M. GST activity continued to increase
      at higher benoxacor concentrations (10 and 100 [mu]M), but no further protection
      was observed. Total GST activity with metolachlor as a substrate increased 2.6-
      to 3.8-fold in response to 1 [mu]M benoxacor treatment. Total GST activity from
      maize treated with or without 1 [mu]M benoxacor was resolved by fast protein
      liquid chromatography anion-exchange chromatography into four major activities,
      designated activity peaks A, B, C, and D in their order of elution. These GST
      activity peaks were enhanced to varying degrees by benoxacor. Activity peak B
      showed the least induction, whereas activity peak A was absent constitutively and
      thus highly induced by benoxacor. In contrast to earlier reports, there appear to
      be not one, but at least two, major constitutive isozymes (activity peaks A and
      D) having activity with metolachlor as substrate; there were at least three such
      isozymes in benoxacor-treated maize (activity peaks A, C, and D). The elution
      volumes of activity peaks A, B, C, and D were compared with those of partially
      purified maize GST I and GST II; also, the reactivity of polypeptides in these
      activity peaks with antisera to GST I or GST I/III (mixture) was evaluated.
      Evidence from these experiments indicated that activity peak B contained GST I,
      and activity peak C contained GST II and GST III. Activity peaks A and D
      contained unique GSTs that may play a major role in metolachlor metabolism and in
      the safening activity of benoxacor in maize. Isozymes present in activity peaks A
      and D were not detected in earlier reports because of the very low activity with
      the artificial substrate 1-chloro-2,4-dinitrobenzene. Immunoblotting experiments
      also indicated the presence of numerous unidentified GST subunits, including
      multiple subunits in chromatography fractions containing single peaks of GST
      activity; this is indicative of the likely complexity and diversity of the maize
      GST enzyme family.

PMID- 12231868
TI  - Comparative Induction of Nitrate and Nitrite Uptake and Reduction Systems by
      Ambient Nitrate and Nitrite in Intact Roots of Barley (Hordeum vulgare L.)
      Seedlings.
AB  - The induction by ambient NO3- and NO2- of the NO3- and NO2- uptake and reduction
      systems in roots of 8-d-old intact barley (Hordeum vulgare L.) seedlings was
      studied. Seedlings were induced with concentrations of NaNO3 or NaNO2 ranging
      from 0.25 to 1000 [mu]M. Uptake was determined by measuring the depletion of
      either NO3- or NO2- from uptake solutions. Enzyme activities were assayed in
      vitro using cell-free extracts. Uptake and reduction systems for both NO3- and
      NO2- were induced by either ion. The Km values for NO3- and NO2- uptake induced
      by NO2- were similar to those for uptake induced by NO3-. Induction of both the
      uptake and reduction systems was detected well before any NO3- or NO2- was found
      in the roots. At lower substrate concentrations of both NO3- and NO2- (5-10
      [mu]M), the durations of the lag periods preceding induction were similar.
      Induction of uptake, as a function of concentration, proceeded linearly and
      similarly for both ions up to about 10 [mu]M. Then, while induction by NO3-
      continued to increase more slowly, induction by NO2- sharply decreased between 10
      and 1000 [mu]M, apparently due to NO2- toxicity. In contrast, induction of NO3-
      reductase (NR) and NO2- reductase (NiR) by NO2- did not decrease above 10 [mu]M
      but rather continued to increase up to a substrate concentration of 1000 [mu]M.
      NO3- was a more effective inducer of NR than was NO2-; however, both ions equally
      induced NiR. Cycloheximide inhibited the induction of both uptake systems as well
      as NR and NiR activities whether induced by NO3- or NO2-. The results indicate
      that in situ NO3- and NO2- induce both uptake and reduction systems, and the
      accumulation of the substrates per se is not obligatory.

PMID- 12231869
TI  - Identification of the Main Species of Tetrapyrrolic Pigments in Envelope
      Membranes from Spinach Chloroplasts.
AB  - The chlorophyll precursors protochlorophyllide and chlorophyllide were identified
      in purified envelope membranes from spinach (Spinacia oleracea) chloroplasts.
      This was shown after pigment separation by high performance liquid chromatography
      (HPLC) using specific fluorescence detection for these compounds.
      Protochlorophyllide and chlorophyllide concentrations in envelope membranes were
      in the range of 0.1 to 1.5 nmol/mg protein. Chlorophyll content of the envelope
      membranes was extremely low (0.3 nmol chlorophyll a/mg protein), but the molar
      ratios of protochlorophyllide and chlorophyllide to chlorophyll were 100 to 1000
      times higher in envelope membranes than in thylakoid membranes. Therefore,
      envelope tetrapyrrolic pigments consist in large part (approximately one-half) of
      nonphytylated molecules, whereas only 0.1% of the pigments in thylakoids are
      nonphytylated molecules. Clear-cut separation of protochlorophyllide and
      chlorophyllide by HPLC allowed us to confirm the presence of a slight
      protochlorophyllide reductase activity in isolated envelope membranes from fully
      developed spinach chloroplasts. The enzyme was active only when envelope
      membranes were illuminated in the presence of NADPH.

PMID- 12231870
TI  - Short-Term Regulation of Crassulacean Acid Metabolism Activity in a Tropical
      Hemiepiphyte, Clusia uvitana.
AB  - Diel courses of net CO2 exchange of leaves were studied in Clusia uvitana
      (Clusiaceae), a tropical Crassulacean acid metabolism (CAM) hemiepiphyte, growing
      in the crown of a 47-m tall kapok tree on Barro Colorado Island, Panama.
      Measurements on days without precipitation showed that net uptake of atmospheric
      CO2 occurred at night, a feature of CAM, as well as in the early morning and late
      afternoon. During 36 h of almost continuous rainfall, nocturnal net CO2 uptake
      was abolished and the diel pattern of net CO2 exchange became similar to that of
      a C3 plant. Exposing well-watered, potted plants of Clusia in the laboratory to
      temperatures and photosynthetic photon flux densities similar to those during the
      tropical rainstorm also abolished nocturnal net CO2 uptake. In contrast,
      Kalanchoe pinnata (Crassulaceae), an obligate CAM plant, still showed net CO2
      dark fixation following the same low-light and moderate-temperature conditions,
      albeit at decreased rates. During these 12-h photoperiods, titratable acidity in
      Clusia increased slightly above its high level measured at the end of the
      previous dark period, whereas in Kalanchoe, the acid content decreased by about
      40%. A survey among outer canopy leaves of Clusia on Barro Colorado Island showed
      that leaves that exhibited little or no nocturnal acidification maintained high
      levels of H+ at dawn and dusk. Progressively lower levels of H+ at dusk were
      accompanied by progressively higher nocturnal increases in H+. The data suggest
      that in C. uvitana the rapid switching between CAM- and C3-type carbon fixation
      that may occur within 24 h in response to environmental changes is controlled by
      the acidity status of the leaves in the light. Nocturnal CO2 fixation is enhanced
      by conditions that decrease the organic acid content during the light period.

PMID- 12231871
TI  - Nitrate Fluxes and Nitrate Reductase Activity of Suspension-Cultured Tobacco
      Cells (Effects of Internal and External Nitrate Concentrations).
AB  - Cell suspensions of tobacco (Nicotiana tabacum L., cv KY14) were used to
      determine the responses of NO3- uptake and NO3- reductase activity (NRA) to
      exogenous NO3- levels in the absence of long-distance NO3- transport. Tobacco
      cells grown with complete Murashige and Skoog medium for 7 d were subcultured for
      3 d with NH4+-free media containing 0, 5, 10, 20, 30, and 40 mM NO3-. Cell NO3-,
      in vitro NRA, NO3- influx, and efflux of cell NO3- were determined. The NRA
      increased as cell NO3- increased. Cell NO3- efflux values increased as cell NO3-
      level increased. Cells with low intracellular NO3- had greater NO3- influx than
      cells with high intracellular NO3-. Woolf-Augustinsson-Hofstee transformations of
      the NO3- influx kinetic data revealed patterns characteristic of a high- and low
      affinity two-component NO3- uptake system. Apparent Vmax values generally
      decreased and Km values increased as cell NO3- concentration increased. The NRA
      of cells supplied with 10 and 20 mM NO3- after 3-d growth in N- free medium
      increased about 5-fold within 2 h and then remained constant for the next 2 h,
      whereas NRA of cells supplied with 5 mM NO3- increased only 2-fold during the 4-h
      period. Intracellular NO3- and other N metabolites associated with cell NO3-
      levels exerted differential effects on the NO3- influx activity and NRA of
      tobacco cells cultured in suspension. Expression of high NRA was correlated with
      both high external and intracellular NO3-, whereas maximum NO3- influx activity
      required a low (depleted) level of cell NO3-.

PMID- 12231872
TI  - Effects of O2 and CO2 on Nonsteady-State Photosynthesis (Further Evidence for
      Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase Limitation).
AB  - The effects of CO2 and O2 on nonsteady-state photosynthesis following an increase
      in photosynthetic photon flux density (PPFD) were examined in Spinacia oleracea
      to investigate the hypotheses that (a) a slow exponential phase (the ribulose-1,5
      bisphosphate carboxylase/oxygenase [Rubisco] phase) of nonsteady-state
      photosynthesis is primarily limited by Rubisco activity and (b) Rubisco
      activation involves two sequential, light-dependent processes as described in a
      previous study (I.E. Woodrow, K.A. Mott [1992] Plant Physiol 99: 298-303).
      Photosynthesis was found to be sensitive to O2 during the Rubisco phase in the
      approach of photosynthesis to steady state. Analyses of this sensitivity to O2
      showed that the control coefficient for Rubisco was approximately equal to 1
      during this phase, suggesting that Rubisco was the primary limitation to
      photosynthesis. O2 had almost no effect on the kinetics (described using a
      relaxation time, [tau] of the Rubisco phase for leaves starting in darkness or
      for leaves starting in low PPFD, but [tau] was substantially higher in the former
      case. CO2 was found to affect both the rate of photosynthesis and the magnitude
      of [tau] for the Rubisco phase. The [tau] value for the Rubisco phase was found
      to be negatively correlated with intercellular CO2 concentration (ci), and leaves
      starting in darkness had higher values of [tau] at any ci than leaves starting in
      low PPFD. The effects of CO2 and O2 on the Rubisco phase are consistent with the
      existence of two sequential, light-dependent processes in the activation of
      Rubisco if neither process is sensitive to O2 and only the second process is
      sensitive to CO2. The implications of the data for the mechanism of Rubisco
      activation and for the effects of stomatal conductance on nonsteady-state
      photosynthesis are discussed.

PMID- 12231873
TI  - Partial Purification of a cis-trans-Isomerase of Zeatin from Immature Seed of
      Phaseolus vulgaris L.
AB  - Investigation of the conversion of exogenous cis-zeatin to trans-zeatin in
      immature seeds of Phaseolus vulgaris L. led to the isolation of a cis-trans
      isomerase from the endosperm. The enzyme was purified more than 2000-fold by
      chromatography on a series of fast protein liquid chromatography (anion exchange,
      gel filtration, and hydrophobic interaction) and concanavalin A columns. The
      enzymic reaction favors conversion from the cis to the trans form and requires
      flavin, light, and dithiothreitol. cis-Zeatin riboside is also a substrate for
      the enzyme. Retention on the concanavalin A column indicated that the enzyme is a
      glycoprotein. The enzyme was stable for at least 8 weeks when stored at -80[deg]
      C. The occurrence of cis-trans-isomerization suggests that cis-zeatin and cis
      zeatin riboside formed by tRNA degradation could be precursors of biologically
      active cytokinins.

PMID- 12231874
TI  - Cellular Localization of Protoporphyrinogen-Oxidizing Activities of Etiolated
      Barley (Hordeum vulgare L.) Leaves (Relationship to Mechanism of Action of
      Protoporphyrinogen Oxidase-Inhibiting Herbicides).
AB  - Seven-day-old, etiolated barley (Hordeum vulgare L. var Post) leaves were
      fractionated into crude and purified etioplast, microsomal, and plasma membrane
      (PM) fractions. Protoporphyrinogen oxidase (Protox) specific activities of crude
      etioplast, purified etioplast, microsome, and PM fractions were approximately 29,
      26, 23, and 12 nmol h-1 mg-1 of protein, respectively. The herbicide acifluorfen
      methyl (AFM), at 1 [mu]M, inhibited Protox activity from crude etioplasts,
      purified etioplasts, microsomes, and PM by 58, 59, 23, and 0% in the absence of
      reductants. Reductants (ascorbate, glutathione [GSH], dithiothreitol [DTT], and
      NADPH) individually reduced the Protox activity of all fractions, except that
      microsomal Protox activity was slightly stimulated by NADPH. Ascorbate, GSH, or a
      combination of the two reductants enhanced Protox inhibition by AFM, and AFM
      inhibition of Protox was greatest in all fractions with DTT. NADPH enhanced AFM
      inhibition significantly only in etioplast fractions. Uroporphyrinogen I (Urogen
      I) and coproporphyrinogen I (Coprogen I) oxidase activities were found in all
      fractions; however, etioplast fractions had significantly more substrate
      specificity for protoporphyrinogen IX (Protogen IX) than the other fractions.
      Urogen I and Coprogen I oxidase activities were unaffected by AFM in all
      fractions, and 2 mM DTT almost completely inhibited these activities from all
      fractions. Diethyldithiocarbamate inhibited PM Protox activity by 62% but had
      less effect on microsome and little or no effect on etioplast Protox. Juglone and
      duroquinone stimulated microsomal and PM Protox activity, whereas the lesser
      effect of these quinones on etioplast Protox activity was judged to be due to PM
      and/or microsomal contaminants. These data indicate that there are microsomal and
      PM Protogen IX-oxidizing activities that are not the same as those associated
      with the etioplast and that these activities are not inhibited in vivo by AFM. In
      summary, these data support the view that the primary source of high
      protoporphyrin IX concentrations in AFM-treated plant tissues is from Protogen IX
      exported by plastids and oxidized by AFM-resistant extraorganellar oxidases.

PMID- 12231875
TI  - Changes in the Activities of Anti-Oxidant Enzymes during Exposure of Intact Wheat
      Leaves to Strong Visible Light at Different Temperatures in the Presence of
      Protein Synthesis Inhibitors.
AB  - Changes in activities of the enzymes involved in the metabolism of active oxygen
      species were followed in homogenates prepared from wheat leaves (Triticum
      aestivum L.) exposed to strong visible light (600 W m-2). The activities of
      superoxide dismutase (SOD), ascorbate peroxidase, and monodehydroascorbate
      reductase increased significantly on prolonged illumination of the leaves,
      indicating an increase in the rate of generation of active oxygen species. This
      increase was further exacerbated when high light stress was combined with low
      temperature (8[deg]C). Our results indicate that the increase in activities of
      SOD and ascorbate peroxidase involved de novo protein synthesis that was
      sensitive to the nuclear-directed protein synthesis inhibitor cycloheximide. The
      activity of catalase, on the other hand, decreased on exposure to strong light,
      which could be due to its photolability, particularly at lower temperatures.
      Ascorbate and total carotenoid contents also increased on light treatment of the
      leaves. The induction of the enzymes except for catalase and increase in the
      levels of ascorbate and total carotenoids in response to the stress conditions
      indicate that they play an important role in the protection of higher plants from
      the damaging effects of toxic active species.

PMID- 12231876
TI  - Ripening Physiology of Fruit from Transgenic Tomato (Lycopersicon esculentum)
      Plants with Reduced Ethylene Synthesis.
AB  - The physiological effects of reduced ethylene synthesis in a transgenic tomato
      (Lycopersicon esculentum) line expressing 1-aminocyclopropane-1-carboxylic acid
      (ACC) deaminase enzyme have been examined. Fruit from the transgenic line 5673
      ripen significantly slower than control fruit when removed from the vine early in
      ripening. In contrast, fruit that remain attached to the plants ripen much more
      rapidly, exhibiting little delay relative to the control. Ethylene determinations
      on attached fruit revealed that there was significantly more internal ethylene in
      attached than detached fruit. The higher ethylene content can fully account for
      the observed faster on-the-vine ripening. All of the data are consistent with a
      catalytic role for ethylene in promoting many, although not all, aspects of fruit
      ripening. Biochemical analyses of transgenic fruit indicated no significant
      differences from controls in the levels of ACC oxidase or polygalacturonase.
      Because transgenic fruit are significantly firmer than controls, this last result
      indicates that other enzymes may have a significant role in fruit softening.

PMID- 12231877
TI  - Phosphorylation and Dephosphorylation of Guard-Cell Proteins from Vicia faba L.
      in Response to Light and Dark.
AB  - Phosphorylation and dephosphorylation of proteins were investigated in guard-cell
      protoplasts from Vicia faba L. When guard-cell protoplasts were incubated with
      32Pi in the dark for 80 min, several proteins, with molecular masses of 42, 40,
      34, 32, 26, and 19 kD, were phosphorylated. Illumination of the dark-adapted
      protoplasts with red light caused dephosphorylation of the 26-kD protein, but
      there was no detectable change in levels of phosphorylation in other proteins. In
      the dephosphorylation of the 26-kD protein, far-red light of 730 nm was most
      effective, but when the light was turned off, the protein was phosphorylated to
      the original level within 10 min. Subcellular fractionation of guard-cell
      protoplasts indicated that the 26-kD protein was located in the chloroplast. The
      migration pattern of the 26-kD protein was exactly the same as the light
      harvesting Chl a/b protein complex of photosystem II (LHCPII) from Vicia
      mesophyll cells on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The
      dephosphorylated 26-kD protein was phosphorylated by adding sodium hydrosulfite,
      a strong reducing agent, under the far-red illumination of guard-cell
      protoplasts. The magnitude of dephosphorylation by red light (660 nm) was
      increased by 3-(3,4-dichlorophenyl)-1,1-dimethylurea, an electron transfer
      inhibitor of photosystem II (PSII). Light-induced dephosphorylation was inhibited
      by 1 nM okadaic acid, an inhibitor of serine/threonine protein phosphatase. From
      these results, it is concluded that the 26-kD protein is LHCPII and that LHCPII
      is present mostly in the phosphorylated form in the dark and is dephosphorylated
      by type 2A protein phosphatase under the light absorbed by photosystem I in Vicia
      guard-cell protoplasts.

PMID- 12231878
TI  - Chalcone Synthase and Flavonol Accumulation in Stigmas and Anthers of Petunia
      hybrida.
AB  - Flavonol aglycones are required for pollen germination in petunia (Petunia
      hybrida L.). Mutant plants lacking chalcone synthase (CHS), which catalyzes the
      first committed step in flavonoid synthesis, do not accumulate flavonols and are
      self-sterile. The mutant pollen can be induced to germinate by supplementing it
      with kaempferol, a flavonol aglycone, either at the time of pollination or by
      addition to an in vitro germination system. Biochemical complementation occurs
      naturally when the mutant, flavonol-deficient pollen is crossed to wild-type,
      flavonoid-producing stigmas. We found that successful pollination depends on
      stigma maturity, indicating that flavonol aglycone accumulation may be
      developmentally regulated. Quantitative immunoblotting, in vitro and in vivo
      pollen germination, and high-performance liquid chromatographic analyses of
      stigma and anther extracts were used to determine the relationship between CHS
      levels and flavonol aglycone accumulation in developing petunia flowers. Although
      substantial levels of CHS were measured, we detected no flavonol aglycones in
      wild-type stigma or anther extracts. Instead, the occurrence of a conjugated form
      (flavonol glycoside) suggests that a mechanism may operate to convert glycosides
      to the active aglycone form.

PMID- 12231879
TI  - Correlation between Ornithine Decarboxylase and Putrescine in Tomato Plants
      Infected by Citrus Exocortis Viroid or Treated with Ethephon.
AB  - We have investigated the arginine decarboxylase (ADC, EC 4.1.1.19) and ornithine
      decarboxylase (ODC, EC 4.1.1.17) activities and the levels of conjugated
      polyamines to explain the decrease of free putrescine level caused by citrus
      exocortis viroid (CEVd) and ethephon treatment in tomato (Lycopersicon esculentum
      Mill. cv Rutgers) plants (J.M. Belles, J. Carbonell, V. Conejero [1991] Plant
      Physiol 96: 1053-1059). This decrease correlates with a decrease in ODC activity
      in CEVd-infected or ethephon-treated plants; ADC activity was not altered. CEVd
      infection had no effect on polyamine conjugates, and ethephon produced a decrease
      in putrescine conjugates. Interference with ethylene action by silver ions
      prevented the decrease in ODC activity and in free and conjugated putrescine. It
      is suggested that changes in putrescine level after CEVd infection and ethephon
      treatment are regulated via ODC activity and that conjugation is not involved.

PMID- 12231880
TI  - Mitochondrial Contribution to Photosynthetic Metabolism (A Study with Barley
      (Hordeum vulgare L.) Leaf Protoplasts at Different Light Intensities and CO2
      Concentrations).
AB  - An oligomycin concentration that specifically inhibits oxidative phosphorylation
      was added to isolated barley (Hordeum vulgare L.) leaf protoplasts at various
      irradiances and carbon dioxide concentrations. At saturating as well as low light
      intensities, photosynthetic oxygen evolution was decreased as a result of the
      oligomycin treatment, whereas no effect was observed at intermediate light
      intensities. This was the same for photorespiratory and nonphotorespiratory
      conditions. These results were confirmed by measurements of fluorescence
      quenching under the same conditions. Metabolite analysis in the presence of
      oligomycin revealed a drastic decrease in the mitochondrial and cytosolic ATP/ADP
      ratios, whereas there was little or no effect on the chloroplastic ratio.
      Concomitantly, sucrose phosphate synthase activity was reduced. Under high
      irradiances, this inhibition of sucrose synthesis by oligomycin apparently caused
      a feedback inhibition on the Calvin cycle and the photosynthetic activity. Under
      low irradiances, a feedback regulation compensated, indicating that light was
      more limiting than the activity of regulative enzymes. Thus, the importance of
      mitochondrial respiratory activity might be different in different metabolic
      situations. At saturating light, the oxidation of excess photosynthetic redox
      equivalents is required to sustain a high rate of photosynthesis. At low light,
      the supply of ATP to the cytosol might be required to support biosynthetic
      reactions.

PMID- 12231881
TI  - Purification and Characterization of 3-Methylcrotonyl-Coenzyme A Carboxylase from
      Higher Plant Mitochondria.
AB  - 3-Methylcrotonyl-coenzyme A (CoA) carboxylase was purified to homogeneity from
      pea (Pisum sativum L.) leaf and potato (Solanum tuberosum L.) tuber mitochondria.
      The native enzyme has an apparent molecular weight of 530,000 in pea leaf and
      500,000 in potato tuber as measured by gel filtration. Polyacrylamide gel
      electrophoresis in the presence of sodium dodecyl sulfate disclosed two
      nonidentical subunits. The larger subunit (B subunit) is biotinylated and has an
      apparent molecular weight of 76,000 in pea leaf and 74,000 in potato tuber. The
      smaller subunit (A subunit) is biotin free and has an apparent molecular weight
      of 54,000 in pea leaf and 53,000 in potato tuber. The biotin content of the
      enzyme is 1 mol/133,000 g of protein and 1 mol/128,000 g of protein in pea leaf
      and potato tuber, respectively. These values are consistent with an A4B4
      tetrameric structure for the native enzyme. Maximal 3-methylcrotonyl-CoA
      carboxylase activity was found at pH 8 to 8.3 and at 35 to 38[deg]C in the
      presence of Mg2+. Kinetic constants (apparent Km values) for the enzyme
      substrates 3-methylcrotonyl-CoA, ATP, and HCO3- were: 0.1 mM, 0.1 mM, and 0.9 mM,
      respectively, for pea leaf 3-methylcrotonyl-CoA carboxylase and 0.1 mM, 0.07 mM,
      and 0.34 mM, respectively, for potato tuber 3-methylcrotonyl-CoA carboxylase. A
      steady-state kinetic analysis of the carboxylase-catalyzed carboxylation of 3
      methylcrotonyl-CoA gave rise to parallel line patterns in double reciprocal plots
      of initial velocity with the substrate pairs 3-methylcrotonyl-CoA plus ATP and 3
      methylcrotonyl-CoA plus HCO3- and an intersecting line pattern with the substrate
      pair HCO3- plus ATP. It was concluded that the kinetic mechanism involves a
      double displacement. Purified 3-methylcrotonyl-CoA carboxylase was inhibited by
      end products of the reaction catalyzed, namely ADP and orthophosphate, and by 3
      hydroxy-3-methylglutaryl-CoA. Finally, as for the 3-methylcrotonyl-CoA
      carboxylases from mammalian and bacterial sources, plant 3-methylcrotonyl-CoA
      carboxylase was sensitive to sulfhydryl and arginyl reagents.

PMID- 12231882
TI  - Iron Deficiency Induced by Chrysobactin in Saintpaulia Leaves Inoculated with
      Erwinia chrysanthemi.
AB  - In this communication, we examine the fate of iron during soft rot pathogenesis
      caused by Erwinia chrysanthemi on its host, Saintpaulia ionantha. The spread of
      soft rot caused by this enterobacterium was previously shown to depend on a
      functional genetic locus encoding a high-affinity iron assimilation system
      involving the catechol-type siderophore chrysobactin. Leaf intercellular fluid
      from healthy plants was analyzed with regard to the iron content and its
      availability for bacterial growth. It was compared to the fluid from diseased
      plants for the presence of strong iron ligands, using a new approach based on the
      iron-binding property of an ion-exchange resin. Further characterization allowed
      the identification of chrysobactin in diseased tissues, thus providing the first
      evidence for the external release of a microbial siderophore during pathogenesis.
      Competition for nutritional iron was also studied through a plant-bacterial cell
      system: iron incorporated into plant ferritin appeared to be considerably reduced
      in bacteria-treated suspension soybean cells. The same effect was visualized
      during treatment of soybean cells with axenic leaf intercellular fluid from E.
      chrysanthemi-inoculated saintpaulia leaves or with chrysobactin.

PMID- 12231883
TI  - Interaction between Aluminum Toxicity and Calcium Uptake at the Root Apex in Near
      Isogenic Lines of Wheat (Triticum aestivum L.) Differing in Aluminum Tolerance.
AB  - Aluminum (Al) is toxic to plants at pH < 5.0 and can begin to inhibit root growth
      within 3 h in solution experiments. The mechanism by which this occurs is
      unclear. Disruption of calcium (Ca) uptake by Al has long been considered a
      possible cause of toxicity, and recent work with wheat (Triticum aestivum L.
      Thell) has demonstrated that Ca uptake at the root apex in an Al-sensitive
      cultivar (Scout 66) was inhibited more than in a tolerant cultivar (Atlas 66)
      (J.W. Huang, J.E. Shaff, D.L. Grunes, L.V. Kochian [1992] Plant Physiol 98: 230
      237). We investigated this interaction further in wheat by measuring root growth
      and Ca uptake in three separate pairs of near-isogenic lines within which plants
      exhibit differential sensitivity to Al. The vibrating calcium-selective
      microelectrode technique was used to estimate net Ca uptake at the root apex of 6
      d-old seedlings. Following the addition of 20 or 50 [mu]M AlCl3, exchange of Ca
      for Al in the root apoplasm caused a net Ca efflux from the root for up to 10
      min. After 40 min of exposure to 50 [mu]M Al, cell wall exchange had ceased, and
      Ca uptake in the Al-sensitive plants of the near-isogenic lines was inhibited,
      whereas in the tolerant plants it was either unaffected or stimulated. This
      provides a general correlation between the inhibition of growth by Al and the
      reduction in Ca influx and adds some support to the hypothesis that a Ca/Al
      interaction may be involved in the primary mechanism of Al toxicity in roots. In
      some treatments, however, Al was able to inhibit root growth significantly
      without affecting net Ca influx. This suggests that the correlation between
      inhibition of Ca uptake and the reduction in root growth may not be a mechanistic
      association. The inhibition of Ca uptake by Al is discussed, and we speculate
      about possible mechanisms of tolerance.

PMID- 12231884
TI  - Tissue Printing as a Tool for Observing Immunological and Protein Profiles in
      Young and Mature Celery Petioles.
AB  - Tissue printing onto membranes such as nitrocellulose is a technique employed to
      study the localization of proteins, nucleic acids, and soluble metabolites from
      freshly cut tissue slices. We probed tissue prints of young and mature celery
      (Apium graveolens) petioles with antibodies raised against two proteins, spinach
      ribulose-1,5-bisphosphate carboxylase and tomato fruit catalase. The purposes of
      this study were to determine if these proteins are developmentally regulated and
      to determine if the patterns and intensities of cross-reactivity of antibodies on
      tissue blots corresponded only to the presence of specific epitopes or was
      related to the amount of protein present in any given area on the tissue prints.
      Different and distinct cross-reactivity patterns were observed with each of the
      two antibodies used. Tissue prints from young and mature tissues also showed
      differences in antibody cross-reactivity. Comparison of Coomassie blue staining
      patterns with antibody reactivity patterns showed that there is little
      relationship between tissue protein concentration and antibody reactivity.

PMID- 12231885
TI  - Demonstration of a Senescence Component in the Regulation of the Mannopine
      Synthase Promoter.
AB  - Regulation of the mannopine synthase (mas) promoter during senescence in leaves
      and flowers of tobacco (Nicotiana tabacum) plants was investigated. In plants
      transformed with a mas 5[prime]-[beta]-glucuronidase (GUS)-mas 3[prime]
      transcriptional fusion, we observed that following the onset of senescence in
      either intact or excised leaves of the transgenic lines, GUS activity increased
      significantly, whereas in excised leaves in which the senescence process was
      inhibited, GUS activity increased only marginally. During flower petal senescence
      in the transgenic tobacco, GUS activity increased approximately 6-fold over
      preanthesis- and anthesis-stage flowers.

PMID- 12231886
TI  - Pollen Expression of Herbicide Target Site Resistance Genes in Annual Ryegrass
      (Lolium rigidum).
AB  - Herbicide resistance can occur either through target-site insensitivity or by
      nontarget site-based mechanisms. Two herbicide-resistant biotypes of Lolium
      rigidum Gaud., one resistant to acetolactate synthase (ALS)-inhibiting herbicides
      (biotype WLR1) and the other resistant to acetyl CoA carboxylase (ACCase)
      inhibiting herbicides (biotype WLR96) through target-site insensitivity at the
      whole plant and enzymic levels, were found to express this resistance in the
      pollen. Pollen produced by resistant biotypes grew uninhibited when challenged
      with herbicide, whereas that from a susceptible biotype was inhibited. A third
      biotype, SLR31, resistant to ACCase-inhibiting and certain ALS-inhibiting
      herbicides at the whole plant level through nontarget site-based mechanisms, did
      not exhibit this expression in the pollen. The technique described may form the
      basis for a rapid screen for certain nuclear-encoded, target site-based herbicide
      resistance mechanisms.

PMID- 12231887
TI  - Control of mRNA Stability in Higher Plants.

PMID- 12231888
TI  - Probing Plasmodesmal Transport with Plant Viruses.

PMID- 12231889
TI  - Rapid Production of Multiple Independent Lines of Fertile Transgenic Wheat
      (Triticum aestivum).
AB  - Improvement of wheat (Triticum aestivum) by biotechnological approaches is
      currently limited by a lack of efficient and reliable transformation methodology.
      In this report, we detail a protocol for transformation of a highly embryogenic
      wheat cultivar, Bobwhite. Calli derived from immature embryos, 0.5 to 1 mm long,
      were bombarded with microprojectiles coated with DNA containing as marker genes
      the bar gene, encoding phosphinothricin-resistance, and the gene encoding [beta]
      glucuronidase (GUS), each under control of a maize ubiquitin promoter. The
      bombardment was performed 5 d after embryo excision, just after initiation of
      callus proliferation. The ability of plantlets to root in the presence of 1 or 3
      mg/L of bialaphos was the most reliable selection criteria used to identify
      transformed plants. Stable transformation was confirmed by marker gene expression
      assays and the presence of the bar sequences in high molecular weight chromosomal
      DNA of the resultant plants. Nine independent lines of fertile transgenic wheat
      plants have been obtained thus far, at a frequency of 1 to 2 per 1000 embryos
      bombarded. On average, 168 d elapsed between embryo excision for bombardment and
      anthesis of the T0 plants. The transmission of both the resistance phenotype and
      bar DNA to the T1 generation verified that germline transformation had occurred.

PMID- 12231890
TI  - C4 Photosynthetic Gene Expression in Light- and Dark-Grown Amaranth Cotyledons.
AB  - The patterns of expression for genes encoding several C4 photosynthetic enzymes
      were examined in light-grown and dark-grown (etiolated) cotyledons of amaranth
      (Amaranthus hypochondriacus), a dicotyledonous C4 plant. The large subunit and
      small subunit of ribulose-1,5-bisphosphate carboxylase (RuBPCase),
      phosphoenolpyruvate carboxylase (PEPCase), and pyruvate orthophosphate dikinase
      (PPdK) were all present in the cotyledons by d 2 after planting when the
      seedlings first emerged from the seed coat. Kranz anatomy was apparent in light
      grown cotyledons throughout development, and the overall patterns of C4 gene
      expression were similar to those recently described for developing amaranth
      leaves (J.L. Wang, D.F. Klessig, J.O. Berry [1992] Plant Cell 4: 173-184).
      RuBPCase mRNA and proteins were present in both bundle sheath and mesophyll cells
      in a C3-like pattern during early development and became progressively more
      localized to bundle sheath cells in the C4-type pattern as the cotyledons
      expanded over 2 to 7 d. PEPCase and PPdK polypeptides were localized to mesophyll
      cells throughout development, even though PEPCase transcripts were detected in
      both bundle sheath and mesophyll cells. Kranz anatomy also developed in
      cotyledons grown in complete darkness. In 7-d-old dark-grown cotyledons,
      RuBPCase, PPdK, and PEPCase were all localized to the appropriate cell types,
      although at somewhat lower levels than in light-grown cotyledons. These findings
      demonstrate that the leaves and postembryonic cotyledons of amaranth undergo
      common developmental programs of C4 gene expression during maturation.
      Furthermore, light is not required for the cell-type-specific expression of genes
      encoding RuBPCase and other photosynthetic enzymes in this dicotyledonous C4
      plant.

PMID- 12231891
TI  - Calcium Retrieval from Vacuolar Pools (Characterization of a Vacuolar Calcium
      Channel).
AB  - Voltage patch-clamp experiments at the whole-vacuole and single-channel levels
      were employed to study the retrieval of Ca2+ from vacuoles into the cytoplasm in
      sugar beet cell (Beta vulgaris L.) suspension cultures. Channels allowing the
      movement of Ca2+ out of the vacuole were identified at physiological conditions
      of pH, vacuolar membrane potential, and vacuole/cytoplasm Ca2+ concentrations.
      The operation of the channel was voltage dependent and inositol-1,4,5
      triphosphate insensitive and displayed high selectivity for Ca2+ ions. These
      channels bear similarities to the dihydropyridine-sensitive L-type Ca2+ channels
      from animal cells. Bay K-8644, an agonist, increased the frequency of channel
      openings, whereas nifedipine, an antagonist, reduced the channel activity. Both
      effects were elicited only from the vacuolar side of the channel. Channel
      activities were also inhibited by verapamil, La3+, and cytoplasmic Ca2+
      concentrations higher than 1 x 10-6 M. The modulation of the channel currents by
      cytoplasmic Ca2+ would suggest the role of these channels in triggering the
      initiation of signal transduction processes in plant cells.

PMID- 12231892
TI  - Effect of High Physiological Temperatures on NAD+ Content of Green Leaf
      Mitochondria (Apparent Inhibition of Glycine Oxidation).
AB  - We observed a rapid decline in the rate of glycine oxidation by purified pea
      (Pisum sativum L.) leaf mitochondria preincubated at 40[deg]C for 2 min. In
      contrast, exogenous NADH and succinate oxidations were not affected by the heat
      treatment. We first demonstrated that the inhibition of glycine oxidation was not
      attributable to a direct effect of high temperatures on glycine
      decarboxylase/serine hydroxymethyltransferase. We observed that (a) addition of
      NAD+ to the incubation medium resulted in a resumption of glycine-dependent O2
      uptake by intact mitochondria, (b) addition of NAD+ to the suspending medium
      prevented the decline in the rate of glycine-dependent O2 consumption by pea leaf
      mitochondria incubated at 40[deg]C, (c) NAD+ concentration in the matrix space
      collapses within only 5 min of warm temperature treatment, and (d) mitochondria
      treated with the NAD+ analog N-4-azido-2-nitrophenyl-4-aminobutyryl-3[prime]-NAD+
      retained high rates of glycine-dependent O2 uptake after preincubation at
      40[deg]C. Therefore, we conclude that the massive and rapid efflux of NAD+,
      leading to the apparent inhibition of glycine oxidation, occurs through the
      specific NAD+ carrier present in the inner membrane of plant mitochondria.
      Finally, our data provide further evidence that NAD+ is not firmly bound to the
      inner membrane.

PMID- 12231893
TI  - Sugar and Organic Acid Accumulation in Guard Cells of Vicia faba in Response to
      Red and Blue Light.
AB  - Changes in neutral sugar and organic acid content of guard cells were quantitated
      by high-performance liquid chromatography during stomatal opening in different
      light qualities. Sonicated Vicia faba epidermal peels were irradiated with 10
      [mu]mol m-2 s-1 of blue light, a fluence rate insufficient for the activation of
      guard cell photosynthesis, or 125 [mu]mol m-2 s-1 of red light, in the presence
      of 1 mM KCl, 0.1 mM CaCl2. The low-fluence-rate blue light stimulated an average
      net stomatal opening of 4.7 [mu]m in 2 h, whereas the saturating fluence rate of
      red light stimulated an average net opening of 3.8 [mu]m in 2 h. Under blue
      light, the malate content of guard cells increased to 173% of the initial level
      during the first 30 min of opening and declined as opening continued. Sucrose
      levels continuously rose throughout the blue light-stimulated opening, reaching
      215% of the initial level after 2 h. The starch hydrolysis products maltose and
      maltotriose remained elevated at all times. Under red light, guard cells showed
      very little increase in organic acid or maltose levels, whereas sucrose levels
      increased to 208% of the initial level after 2 h. Total measured organic
      metabolite concentrations were correlated with stomatal apertures in all cases
      except where substantial malate increases occurred. These results support the
      hypothesis that light quality modulates alternative mechanisms of osmotic
      accumulation in guard cells, including potassium uptake, photosynthetic sugar
      production, and starch breakdown.

PMID- 12231894
TI  - Selected Components of the Shade-Avoidance Syndrome Are Displayed in a Normal
      Manner in Mutants of Arabidopsis thaliana and Brassica rapa Deficient in
      Phytochrome B.
AB  - Several growth parameters associated with the phytochrome-mediated shade
      avoidance syndrome have been measured in seedlings and mature plants of a wild
      type and a hy3 mutant of Arabidopsis thaliana deficient in phytochrome B. Growth
      parameters were compared in plants grown in either white light (high red:far-red
      [R:FR] ratio) or white light plus added far-red (FR) light (low R:FR ratio). Wild
      type Arabidopsis exhibited increased hypocotyl and petiole extension under a low,
      compared with a high, R:FR ratio. The hy3 mutant did not respond to low R:FR
      ratio by increase in hypocotyl or petiole length. Extension growth of wild-type
      plants was stimulated by brief end-of-day FR pulses, but similar treatment had no
      effect on extension growth of hy3 mutant plants. However, some responses to low
      R:FR ratio seen in the wild-type plants were also evident in the hy3 mutants. The
      number of days to bolting, the developmental stage at bolting, the leaf area, and
      the specific stem weight (weight per unit of length) all decreased in the wild
      type and hy3 seedlings in response to low R:FR ratio. Low R:FR ratio caused a
      larger decrease in leaf area and specific stem weight in the mutant seedlings
      than in wild-type seedlings. The effects of low R:FR ratio on leaf area and
      specific stem weight were opposite to those of the hy3 lesion, which resulted in
      increased leaf area and specific stem weight in comparison with the wild type.
      Both leaf area and specific stem weight responses to low R:FR ratio also were
      unchanged in the ein mutant of Brassica rapa, known to be deficient in
      phytochrome B. These responses represent components of the shade-avoidance
      syndrome, and, consequently, the results indicate that phytochrome B cannot be
      solely responsible for the perception of R:FR ratio and the induction of shade
      avoidance responses. The hypothesis is proposed that different phytochromes may
      be responsible for the regulation of extension growth and the regulation of
      lateral or radial expansion.

PMID- 12231895
TI  - Acquisition of Desiccation Tolerance and Longevity in Seeds of Arabidopsis
      thaliana (A Comparative Study Using Abscisic Acid-Insensitive abi3 Mutants).
AB  - Two new abscisic acid (ABA)-insensitive mutants of Arabidopsis thaliana affected
      in the abi3 locus are described. These new mutants are severely ABA insensitive.
      Like the earlier described abi3-1 and the ABA-deficient and -insensitive double
      mutant aba,abi3, these new mutants vary in the extent of ABA-correlated
      physiological responses. Mutant seeds fail to degrade chlorophyll during
      maturation and show no dormancy, and desiccation tolerance and longevity are
      poorly developed. Carbohydrate accumulation as well as synthesis of LEA or RAB
      proteins are often suggested to be essential for acquisition of desiccation
      tolerance. In this work two points are demonstrated. (a) Accumulation of
      carbohydrates as such does not correlate with acquisition of desiccation
      tolerance or longevity. It is suggested that a low ratio of mono- to oligosac
      charides rather than the absolute amount of carbohydrates controls seed longevity
      or stability to desiccation tolerance. (b) Synthesis of a few assorted proteins,
      which is responsive to ABA in the later part of seed maturation, is not
      correlated with desiccation tolerance or longevity.

PMID- 12231896
TI  - Blue Light-Induced Phosphorylation of a Plasma Membrane-Associated Protein in Zea
      mays L.
AB  - Blue light induces a variety of photomorphogenic responses in higher plants,
      among them phototropic curvature, the bending of seedlings toward a
      unidirectional light source. In dark-grown coleoptiles of maize (Zea mays L.)
      seedlings, blue light induces rapid phosphorylation of a 114-kD protein at
      fluence levels that are sufficient to stimulate phototropic curvature.
      Phosphorylation in response to blue light can be detected in vivo in coleoptile
      tips preincubated in 32Pi or in vitro in isolated membranes supplemented with
      [[gamma]-32P]ATP. Phosphorylation reaches a maximum level in vitro within 2 min
      following an inductive light pulse, but substantial labeling occurs within the
      first 15 s. Isolated membranes remain activated for several minutes following an
      in vitro blue light stimulus, even in the absence of exogenous ATP. Phosphoamino
      acid analysis of the 114-kD protein detected phosphoserine and a trace of
      phosphothreonine. The kinase involved in phosphorylating the protein in vitro is
      not dependent on calcium. The 114-kD protein itself has an apparent binding site
      for ATP, detected by incubating with the nonhydrolyzable analog, 5[prime]-p
      fluorosulfonyl-benzoyladenosine. This result suggests that the 114-kD protein,
      which becomes phosphorylated in response to blue light, may also be capable of
      kinase activity.

PMID- 12231897
TI  - Correlation of Blue Light-Induced Phosphorylation to Phototropism in Zea mays L.
AB  - The physiology of light-induced phototropic curvature has been studied
      extensively in coleoptiles of grasses, particularly in Avena and Zea mays L. In
      Z. mays L., we have found that, in addition to curvature, blue light also induces
      rapid phosphorylation of a 114-kD protein in the tips of coleoptiles, and, in a
      previous report, we reported several characteristics of the phosphorylated
      substrate protein and kinase (J.M. Palmer, T.W. Short, S. Gallagher, W.R. Briggs
      [1993] Plant Physiol 102: 1211-1218). Here, we compare the phosphorylation
      response to several known aspects of phototropism physiology. Blue light-induced
      phosphorylation occurs only in the upper portion of the coleoptile and is absent
      from the node and mesocotyl. The specific activity of phosphorylation is highest
      in the extreme apical portion of the tip, which is also the site of maximal
      sensitivity to phototropic stimuli (A. W. Galston [1959] In Physiology of
      Movements, Encyclopedia of Plant Physiology, Springer, Berlin). Fluence-response
      determinations indicate that light dosage levels that stimulate curvature also
      stimulate phosphorylation. However, the threshold for inducing detectable
      phosphorylation in maize cannot be matched to the threshold for curvature
      induction. The recovery of sensitivity to phototropic stimuli after exposure to
      high fluences of light occurs with kinetics that are very similar to those for
      recovery of the phosphorylation response after a previous high-fluence light
      exposure. In addition, wavelengths of light in the blue and near-ultraviolet
      regions of the spectrum that maximally stimulate phototropic curvature also
      maximally stimulate in vitro phosphorylation in maize. The pattern of stimulation
      matches the absorption spectra of flavoproteins, which have been proposed as
      candidates for blue light photoreceptors.

PMID- 12231898
TI  - Cold-Induced Changes in Freezing Tolerance, Protein Phosphorylation, and Gene
      Expression (Evidence for a Role of Calcium).
AB  - The role of Ca2+ in cold-induced changes in protein phosphorylation, gene
      expression, and development of freezing tolerance has been studied in cell
      suspension cultures of a freezing-tolerant cultivar of alfalfa (Medicago sativa
      spp. falcata cv Anik). Chemical treatments to block Ca2+ channels, antagonize
      calmodulin action, or inhibit protein kinases markedly inhibited the cellular
      capacity to develop cold-induced freezing tolerance but had little effect on cell
      viability. An analysis of phosphoprotein profile by two-dimensional
      polyacrylamide gel electrophoresis revealed that at low temperature the relative
      level of phosphorylation of several proteins increased, whereas that of several
      others decreased. When cold acclimation was carried out in the presence of N-(6
      aminohexyl)-5-chloro-1-naphthalene-sulfonamide hydrochloride, an antagonist of
      calmodulin and Ca2+-dependent protein kinases, or the Ca2+ channel blocker La3+,
      the cold-induced changes in protein phosphorylation were strongly inhibited,
      cells lost their capacity to develop freezing tolerance, and accumulation of
      transcripts of cold acclimation-specific genes was substantially reduced. An
      inhibitor of protein kinases, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine
      dihydrochloride, had less pronounced effects on the cold-induced protein
      phosphorylation and caused only a partial inhibition of the cold-induced
      development of freezing tolerance and accumulation of the transcripts. The level
      of phosphorylation of one protein, of about 15 kD, increased more than 10-fold at
      low temperature and showed a strong positive correlation with cold-induced
      freezing tolerance and gene expression even when the latter were altered with
      various chemical treatments. These results suggest that Ca2+ and protein
      phosphorylation, or perhaps a coupling of the two, play an important role during
      the acquisition of freezing tolerance during cold acclimation.

PMID- 12231899
TI  - Phytochrome Control of the Development of Ascorbate Oxidase Activity in Mustard
      (Sinapis alba L.) Cotyledons.
AB  - The activity of ascorbate oxidase (AOX) in mustard (Sinapis alba L.) cotyledons
      was markedly increased by irradiation with continuous far-red light. The
      involvement of phytochrome in this light-mediated response was demonstrated by
      red/far-red reversibility experiments. To determine immunochemically the contents
      of AOX in cotyledons, the antibody against the enzyme was raised in a rabbit.
      However, the antiserum was not monospecific to AOX; it also recognized
      glycoproteins. To remove antibodies that are specific to a carbohydrate moiety of
      glycoproteins, the anti-AOX antiserum was applied to a horseradish peroxidase
      conjugated Sepharose column. By using the antibodies that were not retained in
      the column, the changes in the content of AOX were followed. Western immunoblot
      profiles revealed that the content of AOX protein in cotyledons notably increased
      after continuous far-red light treatment. Pulse-labeling experiments indicated
      that the synthesis of AOX protein occurred in the cotyledons. These results are
      in good agreement with the hypothesis that phytochrome-mediated increase in AOX
      activity is accompanied by the synthesis of the enzyme.

PMID- 12231900
TI  - Phosphatidate Kinase, a Novel Enzyme in Phospholipid Metabolism (Purification,
      Subcellular Localization, and Occurrence in the Plant Kingdom).
AB  - Microsomal membranes from suspension-cultured Catharanthus roseus cells possess
      an enzymic activity that catalyzes the ATP-dependent phosphorylation of
      phosphatidic acid (PA) to form diacylglycerol pyrophosphate (H. Behrbohm, J.B.
      Wissing [1993] FEBS Lett 315: 95-99). This enzyme activity, PA kinase, was
      purified and characterized. Plasma membranes, obtained from C. roseus microsomes
      by aqueous two-phase partitioning, were extracted, and PA kinase was purified
      3200-fold by applying different chromatographic steps that resulted in a specific
      activity of about 10 [mu]mol min-1 mg-1. Sodium dodecyl sulfate-gel
      electrophoresis of the fractions obtained from the final chromatographic step
      revealed a 39-kD protein that correlated with the enzyme activity; PA kinase
      activity could be eluted from this protein band. Subcellular localization,
      investigated with C. roseus cells, showed that the activity was confined to
      membrane fractions, and at least 80% was associated with plasma membranes. The
      data revealed the same distribution within the cellular membranes of PA kinase as
      reported for diacylglycerol kinase, which is a typical plasma membrane-located
      enzyme. Furthermore, PA kinase activity was detected in the calli of 16 different
      plant species and in the different organs of C. roseus plants and obviously
      occurs ubiquitously in the plant kingdom.

PMID- 12231901
TI  - Induction and Turnover of Nitrate Reductase in Zea mays (Influence of NO3-).
AB  - Zea mays (cv W64A x W182E) was used to investigate the induction and turnover of
      nitrate reductase (NR). In our system, 5 or 10 mM KNO3 gave the best growth over
      a 6-d growing period. With these NO3- levels, NR reached steady-state levels
      after 24 h. For the turnover experiments, the seedlings were transferred to a NO3
      -free medium after a 24-h induction. Shoot NR was less sensitive to the removal
      of NO3- than root NR, which declined almost as soon as NO3- was removed when the
      seedlings were induced with 5 or 10 mM NO3-. With 1 mM NO3-, however, removal of
      NO3- from medium resulted in declines in both NR activity and NO3- in shoot and
      root. Although there was a delay in the degradation of NR protein relative to the
      loss of NR activity, this protein was not reactivated when NO3- was resupplied.
      These results indicate that NO3- regulates NR by influencing the de novo
      synthesis of the NR protein and not by a reversible activation-inactivation of
      that protein.

PMID- 12231902
TI  - Differentiation of the Properties of the Branching Isozymes from Maize (Zea
      mays).
AB  - The multiple forms of branching enzyme (BE) from developing maize (Zea mays)
      endosperm were purified by modification of previous procedures such that amylase
      activity could be eliminated completely from the BE preparation. Three distinct
      assays for BE activity (phosphorylase a stimulation assay, BE linkage assay, and
      iodine stain assay) were used to characterize and differentiate the properties of
      the BE isoforms. This study presents the first evidence that the BE isoforms
      differ in their action on amylopectin. BEI had the highest activity in branching
      amylose, but its rate of branching amylopectin was less than 5% of that of
      branching amylose. Conversely, BEII isoforms had lower rates in branching amylose
      (about 9-12% of that of BEI) and had higher rates of branching amylopectin (about
      6-fold) than BEI. The implication of these findings to the mechanism of
      amylopectin synthesis in vivo are discussed.

PMID- 12231903
TI  - An in Vivo Study of Substrate Specificities of Acyl-Lipid Desaturases and
      Acyltransferases in Lipid Synthesis in Synechocystis PCC6803.
AB  - The cyanobacterium Synechocystis PCC6803 was fed heptanoic acid to study the
      substrate specificities of desaturases and acyltransferases in lipid synthesis.
      This aliphatic acid was elongated to C15, C17, and C19 fatty acids, which were
      incorporated into polar glycerolipids and desaturated. The double bonds were
      located at the [delta]6, [delta]9, [delta]12, and [omega]3 positions of the fatty
      acids. This suggests that the [delta]9 desaturase counts the carbon number from
      the carboxy terminus, whereas the so-called [delta]15 desaturase counts from the
      methyl terminus. The counting mechanisms of the [delta]6 and [delta]12
      desaturases are not fully understood. In the distribution of fatty acids at the
      sn positions of the glycerol moiety, the C17, C18, and C19 fatty acids were
      located at the sn-1 position, whereas the C15 and C16 fatty acids were located at
      the sn-2 position. This suggests that glycerol-3-phosphate acyltransferase
      specifically transfers heptadecanoic, octadecanoic, and nonadecanoic acids,
      whereas 1-acylglycerol-3-phosphate acyltransferase specifically transfers
      pentadecanoic and hexadecanoic acids.

PMID- 12231904
TI  - Feedback Regulation of Nitrate Influx in Barley Roots by Nitrate, Nitrite, and
      Ammonium.
AB  - The short-lived radiotracer 13N was used to study feedback regulation of nitrate
      influx through the inducible high-affinity transport system of barley (Hordeum
      vulgare L. cv Steptoe) roots. Both wild-type plants and the mutant line Az12:Az70
      (genotype nar1a;nar7w), which is deficient in the NADH-specific and NAD(P)H
      bispecific nitrate reductases (R.L. Warner, R.C. Huffaker [1989] Plant Physiol
      91: 947-953) showed strong feedback inhibition of nitrate influx within
      approximately 5 d of exposure to 100 fmu]M nitrate. The result with the mutant,
      in which the flux of nitrogen into reduced products is greatly reduced, indicated
      that nitrate itself was capable of exercising feedback regulation upon its own
      influx. This conclusion was supported by the observation that feedback in wild
      type plants occurred in both the presence and absence of L-methionine
      sulfoximine, an inhibitor of ammonium assimilation. Nitrite and ammonium were
      also found to be capable of exerting feedback inhibition upon nitrate influx,
      although it was not determined whether these ions themselves or subsequent
      metabolites were responsible for the effect. It is suggested that feed-back
      regulation of nitrate influx is potentially mediated through several nitrogen
      pools, including that of nitrate itself.

PMID- 12231905
TI  - Correlations between the 13C Content of Primary and Secondary Plant Products in
      Different Cell Compartments and That in Decomposing Basidiomycetes.
AB  - Relative carbon isotope ratio ([delta]13C values) of primary and secondary
      products from different compartments of annual plants, pine needles, wood, and
      decomposing Basidiomycetes have been determined. An enrichment in 13C was found
      for storage tissues of annual plants, because of the high level of the primary
      storage products sucrose and starch; however, the enrichment was even greater in
      leaf starch. All of these compounds had the same relative 13C enrichment in
      positions 3 and 4 of glucose. Secondary products in conifer needles (lignin,
      lipids) were depleted in 13C by 1 to 2 [per mille (thousand) sign] relative to
      carbohydrates from the same origin. Air pollution caused a small decrease in
      [delta]13C values; however, the relative content of plant products, especially of
      the soluble polar compounds, was also affected. Decomposing fungi showed a global
      accumulation of 13C by 4[per mille (thousand) sign] relative to their substrates
      in wood. Their chitin was enriched by 2[per mille (thousand) sign] relative to
      the cellulose of the wood. Hence, Basidiomycetes preferentially metabolize
      "light" molecules, whereas "heavy" molecules are preferentially polymerized. Our
      results are discussed on the basis of a kinetic isotope effect on the fructose
      1,6-bisphosphate aldolase reaction and of metabolic branching on the level of the
      triose phosphates with varying substrate fluxes.

PMID- 12231906
TI  - Aldoxime-Forming Microsomal Enzyme Systems Involved in the Biosynthesis of
      Glucosinolates in Oilseed Rape (Brassica napus) Leaves.
AB  - Glucosinolates and cyanogenic glucosides are synthesized from amino acids via
      similar intermediates, N-hydroxyamino acids and aldoximes. Microsomal
      preparations from young green leaves of oilseed rape catalyze the NADPH-dependent
      metabolism of homo-phenylalanine and dihomomethionine to the respective
      aldoximes, precursors of 2-phenylethyl and 3-butenyl glucosinolates. Cytochrome P
      450-type enzymes are not involved (in contrast to cyanogenic glucoside
      biosynthesis), because neither activity was affected by carbon monoxide or other
      cytochrome P-450 inhibitors. Copper ions and diethyl pyrocarbonate were potent
      inhibitors of the enzymes, and treatment of microsomes with detergents abolished
      the overall activity. Two distinct enzyme systems with similar properties appear
      to be involved, each specific for a particular substrate. One utilizes
      dihomomethionine and is not active with homophenylalanine or any other amino acid
      tested, and the other is specific for homophenylalanine. From the characteristics
      of these enzymes, it seems that these early steps in glucosinolate biosynthesis
      may be catalyzed by flavin-containing monooxygenases comparable to those found in
      mammalian tissues and elsewhere. The pathways for the biosynthesis of
      glucosinolates and cyanogenic glucosides have apparently evolved independently,
      despite the similar chemical conversions involved.

PMID- 12231907
TI  - [omega]-Hydroxylation of Oleic Acid in Vicia sativa Microsomes (Inhibition by
      Substrate Analogs and Inactivation by Terminal Acetylenes).
AB  - Oleic acid (18:1) is hydroxylated exclusively on the terminal methyl by a
      microsomal cytochrome P-450-dependent system ([omega]-OAH) from clofibrate
      induced Vicia sativa L. (var minor) seedlings (F. Pinot, J.-P. Salaun, H. Bosch,
      A. Lesot, C. Mioskowski, F. Durst [1992] Biochem Biophys Res Commun 184: 183
      193). This reaction was inactivated by two terminal acetylenes: (Z)-9-octadecen
      17-ynoic acid (17-ODCYA) and the corresponding epoxide, (Z)-9,10-epoxyoctadecan
      17-ynoic acid (17-EODCYA). Inactivation was mechanism-based, with an apparent
      binding constant of 21 and 32 [mu]M and half-lives of 16 and 19 min for 17-ODCYA
      and 17-EODCYA, respectively. We have investigated the participation of one or
      more [omega]-hydroxylase isoforms in the oxidation of fatty acids in this plant
      system. Lauric acid (12:0) is [omega]-hydroxylated by the cytochrome P-450
      [omega]-hydroxylase [omega]-LAH (J.-P. Salaun, A. Simon, F. Durst [1986] Lipids
      21: 776-779). Half-lives of [omega]-OAH and [omega]-LAH in the presence of 40
      [mu]M 17-ODCYA were 23 and 41 min, respectively. Inhibition of oleic acid [omega]
      hydroxylation was competitive with linoleic acid (18:2), but noncompetitive with
      lauric acid (12:0). In contrast, oleic acid did not inhibit [omega]-hydroxylation
      of lauric acid. Furthermore, 1-pentadecyltriazole inhibited [omega]-hydroxylation
      of oleic acid but not of lauric acid. These results suggest that distinct
      monooxygenases catalyze [omega]-hydroxylation of medium- and long-chain fatty
      acids in V. sativa microsomes.

PMID- 12231908
TI  - An in Vitro System of Indole-3-Acetic Acid Formation from Tryptophan in Maize
      (Zea mays) Coleoptile Extracts.
AB  - The formation of a product from tryptophan that had the same retention time as
      that of authentic indole-3-acetic acid (IAA) on high performance liquid
      chromatography was detected in crude extracts of maize (Zea mays) coleoptiles.
      The product was identified as IAA by mass spectrometry. The IAA-forming activity
      was co-purified with an indole-3-acetaldehyde (IAAld) oxidase activity by
      chromatography on hydrophobic and gel filtration (GPC-100) columns. During
      purification, the IAA-forming activity, rather than that of IAAld oxidase,
      decreased; but when hemoprotein obtained from the same tissue was added, activity
      recovered to the same level as that of IAAld oxidase. The promotive activity of
      the hemoprotein was confirmed by the result that the activity coincided with
      amounts of the hemoprotein after GPC-100 column chromatography. The hemoprotein
      was characterized and identified as a cytosolic ascorbate peroxidase (T. Koshiba
      [1993] Plant Cell Physiol [in press]). The reaction of the IAA-forming activity
      was apparently one step from tryptophan. The activity was inhibited by 2
      mercaptoethanol. The optimum temperature for the IAA-forming system as well as
      for the IAAld oxidase was 50 to 60[deg]C, and the acitivity at 30[deg]C was one
      third to one-half of that at 60[deg]C. The system did not discriminate the L- and
      D-enantiomers of tryptophan.

PMID- 12231909
TI  - The Elicitation of Ethylene Biosynthesis by a Trichoderma Xylanase Is Not Related
      to the Cell Wall Degradation Activity of the Enzyme.
AB  - A [beta]-1,4-endoxylanase (EIX) isolated from Trichoderma viride elicits plant
      defense responses in certain tobacco (Nicotiana tabacum L.) cultivars in addition
      to its xylan degradation activity. It was not clear whether elicitation occurs by
      cell wall fragments released by the enzymic activity or by the xylanase protein
      interacting directly with the plant cells. We used protoplasts isolated from
      tobacco leaves to test whether the cell wall is required for the stimulation of
      ethylene biosynthesis by EIX. Protoplasts of tobacco (cv Xanthi) responded to
      treatment with the EIX, as indicated by an increased production of ethylene and
      the loss of protoplast viability. Protoplasts prepared from ethylene-pretreated
      leaves produced more ethylene and had higher rates of cell death in response to
      EIX than protoplasts prepared from nonethylene-treated leaves. Protoplasts of an
      EIX-insensitive cultivar of tobacco (Hicks) were insensitive to high
      concentrations of EIX. The addition of a crude cell wall preparation to
      protoplasts during incubation with EIX did not enhance the induction of ethylene
      biosynthesis by nonsaturating as well as saturating concentrations of EIX. These
      data indicate that the xylanase activity of EIX is unrelated to the elicitation
      of ethylene biosynthesis through the production of some cell wall fragment, since
      the protein per se appears capable of eliciting ethylene biosynthesis in
      protoplasts.

PMID- 12231910
TI  - Membrane Response to Diclofop Acid Is pH Dependent and Is Regulated by the
      Protonated Form of the Herbicide in Roots of Pea and Resistant and Susceptible
      Rigid Ryegrass.
AB  - Electrophysiological studies in roots of pea (Pisum sativum L.) and rigid
      ryegrass (Lolium rigidum Gaud.) seedlings were conducted to elucidate the
      mechanism involved in the membrane response to the herbicide diclofop. In pea, a
      dicotyledonous plant insensitive to diclofop, membrane depolarization at varying
      pH values and herbicide concentrations increased at higher concentrations of the
      protonated form of diclofop acid (pKa 3.57). In unbuffered nutrient solution (pH
      5.7), diclofop acid (50 [mu]M) depolarized the membrane potential (Em) in roots
      of both resistant and susceptible biotypes of rigid ryegrass, whereas recovery of
      Em occurred only in the resistant biotype following removal of the herbicide.
      This differential response was correlated with an increase (450%) in the rate of
      acidification of the external solution by the susceptible biotype, and the Em
      differences between biotypes were eliminated in solutions buffered at pH 5.0 or
      6.0. In addition, p-chloromercuribenzene-sulfonic acid did not prevent the
      depolarization of Em by 50 [mu]M diclofop acid. It is concluded that the
      differential membrane response to diclofop acid in herbicide-resistant and 
      susceptible biotypes of rigid ryegrass is due to pH differences at the cell
      wall/plasmalemma interface. Although the membrane response is probably not
      involved in the primary inhibitory effect of diclofop on plant growth, it could
      reduce the concentration of the permeant protonated form of the herbicide and
      possibly could contribute to increased tolerance to diclofop and other weak acid
      herbicides.

PMID- 12231911
TI  - Harpin, An Elicitor of the Hypersensitive Response in Tobacco Caused by Erwinia
      amylovora, Elicits Active Oxygen Production in Suspension Cells.
AB  - Active oxygen (AO) production and a K+/H+ exchange response (XR) are two
      concurrent early events associated with incompatible plant-bacteria interactions
      that result in a hypersensitive response (HR). Recently, a protein, termed
      harpin, produced by Erwinia amylovora has been reported to be the elicitor
      responsible for the HR caused by this pathogen. Although both the bacterium and
      harpin are reported to induce XR in tobacco (Nicotiana tabacum) cell suspensions,
      there have been no reports regarding the concurrent production of AO in this
      system. Here we report that E. amylovora stimulates the AO response, whereas an
      E. amylovora mutant that does not produce harpin does not elicit the AO response.
      In addition, a cell-free preparation of harpin induces AO production. This study
      indicates that harpin may be the bacterial elicitor of the XR and AO responses
      during the development of E. amylovora-induced HR.

PMID- 12231912
TI  - Regulation of Cytosolic Calcium in Plants.

PMID- 12231913
TI  - Genetic Evidence That the Red-Absorbing Form of Phytochrome B Modulates
      Gravitropism in Arabidopsis thaliana.
AB  - Hypocotyls of dark-grown Arabidopsis seedlings exhibit strong negative
      gravitropism, whereas in red light, gravitropism is strongly reduced. Red/far-red
      light-pulse experiments and analysis of specific phytochrome-deficient mutants
      indicate that the red-absorbing (Pr) form of phytochrome B regulates normal
      hypocotyl gravitropism in darkness, and depletion of Pr by photoconversion to the
      far-red-absorbing form attenuates hypocotyl gravitropism. These studies provide
      genetic evidence that the Pr form of phytochrome has an active function in plant
      development.

PMID- 12231914
TI  - Galactose-Specific Lectins Protect Isolated Thylakoids against Freeze-Thaw
      Damage.
AB  - We have measured freeze-thaw damage to isolated spinach (Spinacia oleracea L.)
      chloroplast thylakoid membranes in the presence of different galactose-specific
      seed lectins to determine whether the binding of proteins to the membrane surface
      can lead to cryoprotection. Of the seven lectins investigated, five were
      protective to different degrees and two showed no measurable effect. Protection
      was afforded by a reduction of the solute permeability of the membranes. This
      reduced the solute influx during freezing and thereby osmotic rupture of the
      thylakoid vesicles during thawing. Using model membranes and fluorescently
      labeled lectins, we could show that the proteins bound exclusively to the
      digalactosyl lipids in the membranes. Binding was a prerequisite for the
      protective effect, because the presence of up to 5 mM galactose in the samples
      completely inhibited both binding of the lectins to thylakoid and model membranes
      and cryoprotection. The degree of binding was, in contrast, not related to the
      cryoprotective efficiency of different lectins; cryoprotection was a function of
      the hydrophobicity of the proteins.

PMID- 12231915
TI  - Density Gradient Study of Victorin-Binding Proteins in Oat (Avena sativa) Cells.
AB  - Victorin-binding proteins (VBPs) in oat (Avena sativa) cells were identified
      using native victorin and anti-victorin polyclonal antibodies. Homogenates of oat
      tissues were fractionated in continuous or discontinuous sucrose density
      gradients or with an aqueous two-phase method, and covalent binding sites of
      victorin were detected by western blotting. In a 20 to 45% (w/w) sucrose
      continuous density gradient, the 100-kD VBP was located in fractions of 37 to 44%
      sucrose, with a peak at 39% sucrose. Based on marker enzyme assays, plasma
      membranes peaked at 39 to 41% sucrose, mitochondria peaked at 41%, but Golgi and
      endoplasmic reticulum were in lower density fractions, peaking at 28 to 29% and
      22 to 24% sucrose, respectively. The 100-kD VBP was not found in plasma membranes
      purified by the aqueous two-phase method or in mitochondria purified by
      discontinuous density gradient centrifugation. Victorin binding to 65- and 45-kD
      proteins was detected in all fractions in the continuous sucrose density
      gradients. The 65- and 45-kD proteins were both detected in purified plasma
      membranes, but only the 65-kD protein was detected in purified mitochondria. The
      subcellular location of VBPs was the same in sensitive and resistant oat cells.

PMID- 12231916
TI  - C4 Photosynthesis (The CO2-Concentrating Mechanism and Photorespiration).
AB  - Despite previous reports of no apparent photorespiration in C4 plants based on
      measurements of gas exchange under 2 versus 21% O2 at varying [CO2],
      photosynthesis in maize (Zea mays) shows a dual response to varying [O2]. The
      maximum rate of photosynthesis in maize is dependent on O2 (approximately 10%).
      This O2 dependence is not related to stomatal conductance, because measurements
      were made at constant intercellular CO2 concentration (Ci); it may be linked to
      respiration or pseudocyclic electron flow. At a given Ci, increasing [O2] above
      10% inhibits both the rate of photosynthesis, measured under high light, and the
      maximum quantum yield, measured under limiting light ([phi]CO2). The dual effect
      of O2 is masked if measurements are made under only 2 versus 21% O2. The
      inhibition of both photosynthesis and [phi]CO2 by O2 (measured above 10% O2) with
      decreasing Ci increases in a very similar manner, characteristically of O2
      inhibition due to photorespiration. There is a sharp increase in O2 inhibition
      when the Ci decreases below 50 [mu]bar of CO2. Also, increasing temperature,
      which favors photorespiration, causes a decrease in [phi]CO2 under limiting CO2
      and 40% O2. By comparing the degree of inhibition of photosynthesis in maize with
      that in the C3 species wheat (Triticum aestivum) at varying Ci, the effectiveness
      of C4 photosynthesis in concentrating CO2 in the leaf was evaluated. Under high
      light, 30[deg]C, and atmospheric levels of CO2 (340 [mu]bar), where there is
      little inhibition of photosynthesis in maize by O2, the estimated level of CO2
      around ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) in the bundle
      sheath compartment was 900 [mu]bar, which is about 3 times higher than the value
      around Rubisco in mesophyll cells of wheat. A high [CO2] is maintained in the
      bundle sheath compartment in maize until Ci decreases below approximately 100
      [mu]bar. The results from these gas exchange measurements indicate that
      photorespiration occurs in maize but that the rate is low unless the
      intercellular [CO2] is severely limited by stress.

PMID- 12231917
TI  - Effects on Photosystem II Function, Photoinhibition, and Plant Performance of the
      Spontaneous Mutation of Serine-264 in the Photosystem II Reaction Center D1
      Protein in Triazine-Resistant Brassica napus L.
AB  - Wild-type and an atrazine-resistant biotype of Brassica napus, in which a glycine
      is substituted for the serine-264 of the D1protein, were grown over a wide range
      of constant irradiances in a growth cabinet. In the absence of serine-264, the
      function of photosystem II (PSII) was changed as reflected by changes in
      chlorophyll fluorescence parameters and in photosynthetic oxygen-evolving
      activity. The photochemical quenching coefficient was lower, showing that a
      larger proportion of the primary quinone acceptor is reduced at all irradiances.
      At low actinic irradiances, the nonphotochemical quenching coefficient was
      higher, showing a greater tendency for heat emission. Decreased rates of light
      limited photosynthesis (quantum yield) and lower oxygen yields per single
      turnover flash were also observed. These changes were observed even when the
      plants had been grown under low irradiances, indicating that the changes in PSII
      function are direct and not consequences of photoinhibition. In spite of the
      lowered PSII efficiency under light-limiting conditions, the light-saturated
      photosynthesis rate of the atrazine-resistant mutant was similar to that of the
      wild type. An enhanced susceptibility to photoinhibition was observed for the
      atrazine-resistant biotype compared to the wild type when plants were grown under
      high and intermediate, but not low, irradiance. We conclude that the replacement
      of serine by glycine in the D1 protein has a direct effect on PSII function,
      which in turn causes increased photoinhibitory damage and increased rates of
      turnover of the D1 protein. Both the intrinsic lowering of light-limited
      photosynthetic efficiency and the increased sensitivity to photoinhibition
      probably contribute to reduced crop yields in the field, to different extents,
      depending on growth conditions.

PMID- 12231918
TI  - A Novel Hydroxyproline-Deficient Arabinogalactan Protein Secreted by Suspension
      Cultured Cells of Daucus carota (Purification and Partial Characterization).
AB  - Arabinogalactan proteins (AGPs) are secreted or membrane-associated glycoproteins
      that have been operationally defined as binding to [beta]-glucosyl Yariv
      artificial antigen, being rich in arabinose and galactose, and containing high
      levels of alanine, serine, and hydroxyproline. Using an anti-AGP monoclonal
      antibody (MAC 207) bound to cyanogen bromide-activated Sepharose 4B, we have
      purified by immunoaffinity chromatography an extracellular AGP from the culture
      medium of suspension-cultured cells of carrot (Daucus carota). The apparent
      molecular mass of this highly glycosylated proteoglycan is 70 to 100 kD as judged
      by sodium dodecyl sulfate-polyacrylamide gels. Although its sugar analysis,
      [beta]-glucosyl Yariv binding, and high alanine, serine, and proline content are
      consistent with it being an AGP, the amino acid composition unexpectedly revealed
      this molecule to have no detectable hydroxyproline. This suggests that this
      glycoprotein is not a "classical" AGP, but represents the first example of a new
      class of hydroxyproline-poor AGPs. Deglycosylation of the AGP with anhydrous
      hydrogen fluoride revealed that the purified proteoglycan contains probably a
      single core protein with an apparent molecular mass of 30 kD. Direct
      visualization of the native AGP in the electron microscope showed ellipsoidal
      putative AGP monomers, approximately 25 nm by 15 nm, that showed a strong
      tendency to self assemble into higher-order structures. Upon desiccation, the
      glycosylated AGP formed paracrystalline arrays visible in the light microscope.
      Polarized Fourier transform infrared microspectroscopy of these arrays
      demonstrated a high degree of polarization of the sugar moieties under these
      conditions. These results put possible constraints on current models of AGP
      structure; a putative role for these novel AGPs as pectin-binding proteins is
      discussed.

PMID- 12231919
TI  - Plant Viability as a Function of Temperature Stress (The Richards Function
      Applied to Data from Freezing Tests of Growing Shoots).
AB  - Frost resistance of growing Salix viminalis L. shoots was determined by rating
      mortality percentage under two commonly used freezing conditions: a condition in
      which plants were encased in crushed ice and another in which plants were
      moistened with tap water prior to freezing. The mortality-temperature data were
      fitted with a logistic function (having a fixed inflection point halfway between
      the asymptotes) and with a Richards function, which is a double asymptotic
      sigmoid function with a variable inflection point. Different frost resistance
      curves were obtained, depending on the freezing conditions used. However,
      conditions were inadequate for efficient ice nucleation under either condition.
      This implies that the applied freezing conditions are not suitable when the
      purpose is to induce and duplicate early ice crystal formation conditions. The
      Richards derivatives were negatively skewed in the one case and positively skewed
      in the other case, giving inflection points, as a function of the upper
      asymptote, situated at 0.37 when shoots were frosted in the presence of ice and
      at 0.81 when shoots were frozen in the presence of added moisture. These values
      differed significantly from 0.50, through which the logistic function would have
      forced the curves. Because of the significant asymmetry in these frost-resistance
      curves, the Richards function led to a more accurate reflection of the
      temperature-mortality course of growing Salix stems than the logistic function.
      The Richards function possesses the flexibility needed to describe plant injury
      response in terms of physical and plant physiological mechanisms. Therefore, the
      Richards function is recommended rather than the logistic function for the
      assessment of frost resistance.

PMID- 12231920
TI  - ADP/ATP Translocator from Pea Root Plastids (Comparison with Translocators from
      Spinach Chloroplasts and Pea Leaf Mitochondria).
AB  - The kinetic properties of the adenosine 5[prime]-diphosphate/adenosine 5[prime]
      triphosphate (ADP/ATP) translocator from pea (Pisum sativum L.) root plastids
      were determined by silicone oil filtering centrifugation and compared with those
      of spinach (Spinacia oleracea L.) chloroplasts and pea leaf mitochondria. In
      addition, the ADP/ATP transporting activities from the above organelles were
      reconstituted into liposomes. The Km(ATP) value of the pea root ADP/ATP
      translocator was 10 [mu]M and that for ADP was 46 [mu]M. Corresponding values of
      the spinach ADP/ATP translocator were 25 [mu]M and 28 [mu]M, respectively.
      Comparable results were obtained for the reconstituted ATP transport activities.
      The transport was highly specific for ATP and ADP. Adenosine 5[prime]
      monophosphate (AMP) caused only a slight inhibition and phosphoenolpyruvate and
      inorganic pyrophosphate caused no inhibition of ATP uptake. With pea root
      plastids and spinach chloroplasts, Km values >1 mM were obtained for ADP-glucose.
      Since the concentrations of ATP and ADP-glucose in the cytosolic compartment of
      spinach leaves have been determined as 2.5 and 0.6 mM, respectively, a transport
      of ADP-glucose by the ADP/ATP translocator does not appear to have any
      physiological significance in vivo. Although both the plastidial and the
      mitochondrial ADP/ATP translocators were inhibited to some extent by
      carboxyatractyloside, no immunological cross-reactivity was detected between the
      plastidial and the mitochondrial proteins. It seems probable that these proteins
      derive from different ancestors.

PMID- 12231921
TI  - Soybean (Glycine max) Nodule Physical Traits Associated with Permeability
      Responses to Oxygen.
AB  - Nodule permeability (P) controls the amount of O2 entering the nodule and is an
      important determinant of N2 fixation. Modulation of water volume in the
      intercellular spaces of the nodule cortex was hypothesized to change the
      effective thickness of a diffusion barrier and account for changes in P. This
      hypothesis was examined by evaluating physical traits of nodules that may affect
      P. The first test of the hypothesis was to determine whether alterations in P may
      result in changing both the density and the air space content of nodules as the
      water content of intercellular spaces was varied. Density of nodules exposed to
      21 kPa O2 increased as the time following detachment from the plant increased
      from 5 to 60 min. Nodules from soybean (Glycine max [L.] Merr.) plants shaded for
      48 h had a lower fractional air space content than nodules from control plants.
      Nodule detachment and prolonged shading decreased P, and the increase in density
      and decrease in fractional air space content associated with decreased P in these
      treatments supports the proposed hypothesis. The second test of the hypothesis
      was to determine whether nodules released water easily in response to water
      potential gradients. The intrinsic capacitance of nodules determined by pressure
      volume analysis was 0.29 MPa-1 and indicated that the tissue can release
      relatively large amounts of water from the symplast with only small changes in
      total nodule water potential. Estimates of the bulk modulus of elasticity ranged
      from 0.91 to 2.60 MPa and indicated a high degree of elasticity. It was concluded
      that the physical properties of nodules were consistent with P modulation by the
      release and uptake of intercellular water in the nodule cortex.

PMID- 12231922
TI  - Growth Distribution during Phototropism of Arabidopsis thaliana Seedlings.
AB  - The elongation rates of two opposite sides of hypocotyls of Arabidopsis thaliana
      seedlings were measured during phototropism by using an infrared imaging system.
      In first positive phototropism, second positive phototropism, and red light
      enhanced first positive phototropism, curvature toward the light source was the
      result of an increase in the rate of elongation of the shaded side and a decrease
      in the rate of elongation of the lighted side of the seedlings. The phase of
      straightening that followed maximum curvature resulted from a decrease in the
      elongation rate of the shaded side and an increase in the elongation rate of the
      lighted side. These data for the three types of blue light-induced phototropism
      tested in this study and for the phase of straightening are all clearly
      consistent with the growth rate changes predicted by the Cholodny-Went theory.

PMID- 12231923
TI  - A Mutant of Arabidopsis thaliana with a Reduced Response to Fusicoccin. I.
AB  - Because fusicoccin (FC) has the the capacity to promote solute uptake, a
      selective procedure for isolating mutants of Arabidopsis thaliana with a reduced
      response to the toxin has been developed. The procedure is based on the
      incubation of A. thaliana seedlings in a solution containing the cation Paraquat
      (Pq) at a concentration that per se does not produce bleaching of the leaves upon
      illumination but does in the presence of FC because of the increased uptake of
      the toxic cation. Using this procedure, we identified, among the progenies of
      2010 M1 ethyl methanesulfonate-mutagenized plants, two mutants that stay green
      after exposure to FC and Pq. Some properties and inheritance of one of the two
      mutants (5-2) are described. Morphology of mutant plants is almost
      indistinguishable from that of the wild type. However, 5-2 seeds germinate and
      produce viable seedlings in the presence of FC plus the aminoglycoside antibiotic
      hygromycin B: plants of the mutant do not wilt when exposed to FC and stomata do
      not open or open only partially. In the presence of FC, the mutant appears less
      responsive than the wild type as far as the increment in fresh weight, the
      enlargement of leaf disc area, or the stimulation of H+ extrusion is concerned.
      Inheritance of the trait is monogenic dominant or semidominant, depending on the
      test used.

PMID- 12231924
TI  - PsaE Is Required for in Vivo Cyclic Electron Flow around Photosystem I in the
      Cyanobacterium Synechococcus sp. PCC 7002.
AB  - Electron transfer rates to P700+ have been determined in wild-type and three
      interposon mutants (psaE-, ndhF-, and psaE- ndhF-) of Synechococcus sp. PCC 7002.
      All three mutants grew significantly more slowly than wild type at low light
      intensities, and each failed to grow photoheterotrophically in the presence of 3
      (3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and a metabolizable carbon source.
      The kinetics of P700+ reduction were similar in the wild-type and mutant whole
      cells in the absence of DCMU. In the presence of DCMU, the P700+ reduction rate
      in the psaE mutant was significantly slower than in the wild type. In the
      presence of DCMU and potassium cyanide, added to inhibit the outflow of electrons
      through cytochrome oxidase, P700+ reduction rates increased for both the psaE-
      and ndhF- strains. The reduction rates for these two mutants were nonetheless
      slower than that observed for the wild-type strain. The further addition of
      methyl viologen caused the rate of P700+ reduction in the wild type to become as
      slow as that for the psaE mutant in the absence of methyl viologen. Given the
      ability of methyl viologen to intercept electrons from the acceptor side of
      photosystem I, this response reveals a lesion in cyclic electron flow in the psaE
      mutant. In the presence of DCMU, the rate of P700+ reduction in the psaE ndhF
      double mutant was very slow and nearly identical with that for the wild-type
      strain in the presence of 2,4-dibromo-3-methyl-6-isopropyl-p-benzoquinone, a
      condition under which physiological electron donation to P700+ should be
      completely inhibited. These results suggest that NdhF- and PsaE-dependent
      electron donation to P700+ occurs only via plastoquinone and/or cytochrome b6/f
      and indicate that there are three major electron sources for P700+ reduction in
      this cyanobacterium. We conclude that, although PsaE is not required for linear
      electron flow to NADP+, it is an essential component in the cyclic electron
      transport pathway around photosystem I.

PMID- 12231925
TI  - Photosystem II Reaction Center Damage and Repair in Dunaliella salina (Green
      Alga) (Analysis under Physiological and Irradiance-Stress Conditions).
AB  - Mechanistic aspects of the photosystem II (PSII) damage and repair cycle in
      chloroplasts were investigated. The D1/32-kD reaction center protein of PSII
      (known as the psbA chloroplast gene product) undergoes a frequent light-dependent
      damage and turnover in the thylakoid membrane. In the model organism Dunaliella
      salina (green alga), growth under a limiting intensity of illumination (100
      [mu]mol of photons m-2 s-1; low light) entails damage, degradation, and
      replacement of D1 every about 7 h. Growth under irradiance-stress conditions
      (2000 [mu]mol of photons m-2 s-1; high light) entails damage to and replacement
      of D1 about every 20 min. Thus, the rate of damage and repair of PSII appears to
      be proportional to the light intensity during plant growth. Low-light-grown cells
      do not possess the capacity for high rates of repair. Upon transfer of low-light
      grown cells to high-light conditions, accelerated damage to reaction center
      proteins is followed by PSII disassembly and aggregation of neighboring reaction
      center complexes into an insoluble dimer form. The accumulation of inactive PSII
      centers that still contain the D1 protein suggests that the rate of D1
      degradation is the rate-limiting step in the PSII repair cycle. Under irradiance
      stress conditions, chloroplasts gradually acquire a greater capacity for repair.
      The induction of this phenomenon occurs with a half-time of about 24 h.

PMID- 12231926
TI  - The Circadian Oscillator Coordinates the Synthesis of Apoproteins and Their
      Pigments during Chloroplast Development.
AB  - Greening has been studied at circadian times of maximal and minimal levels of
      mRNA for the light-harvesting chlorophyll a/b binding protein in photosystem II
      (Cab mRNA) after circadian synchronization of etiolated barley plantlets (Hordeum
      vulgare cv Apex) by heat-shock treatments. It was found that greening occurs
      faster and without a lag period when illumination was started at the time of
      maximal Cab mRNA accumulation. This holds true for the rate of accumulation of
      Cab and early light-inducible protein mRNAs, the levels of their correspondent
      proteins, and the levels of chlorophyll a and b. When illumination was started at
      the time of Cab mRNA minimum, a lag in the appearance of all components mentioned
      above was observed. Under these conditions, the lag in chlorophyll b accumulation
      was by far more pronounced than that found for chlorophyll a. The circadian
      oscillation in the capacity of chlorophyll synthesis appears to be controlled via
      [delta]-aminolevulinic acid ([delta]-ALA) synthesis. [delta]-ALA accumulation
      after levulinic acid treatment is itself under circadian control; the maxima in
      stationary concentrations coincide with those of Cab mRNA levels. The amounts of
      protochlorophyllide and photoconvertible protochlorophyllide showed only minor
      differences between circadian minima and maxima, the levels being slightly lower
      during the time of minimum.

PMID- 12231927
TI  - Passive Proton Conductance Is the Major Reason for Membrane Depolarization and
      Conductance Increase in Chara buckellii in High-Salt Conditions.
AB  - Chara buckellii G.O.A., a salt-tolerant alga, has a less negative membrane
      potential (Em) when cultured in saline medium (artificial Waldsea water) than
      when cultured in freshwater. The cell hyperpolarizes and membrane conductance
      (Gm) decreases when the external medium is changed from Waldsea control solution
      (WCS), a high-salt medium, to low-salt medium containing sufficient sorbitol to
      generate the same osmotic potential as WCS. Banding pattern and proton flux
      experiments show that C. buckellii has higher passive proton influx in the
      alkaline band in high-salt medium than in low-salt medium. Decrease of the
      passive proton influx by darkness or low external pH dramatically hyperpolarizes
      the membrane and decreases the conductance. The pH dependence curves of Em and Gm
      also indicate the existence of high passive proton conductance (GH) in C.
      buckellii. Ion substitution experiments show that Em and Gm of saltwater cells
      are not dependent on K+, Na+, Cl-, or SO42+. Mg2+ also affects Em and Gm, but its
      effect is probably on GH. We conclude that GH is the most important cause of the
      membrane depolarization and conductance increase in the saltwater alga C.
      buckellii.

PMID- 12231928
TI  - Fructan Hydrolysis Drives Petal Expansion in the Ephemeral Daylily Flower.
AB  - Dry weight, water content, soluble carbohydrate content, and carbohydrate
      composition of daylily (Hemerocallis hybrid cv Cradle Song) flower petals were
      monitored in the 3 d leading up to full opening and in the first day of
      senescence. Timing of events was related to the time (hour 0) when flower
      expansion was 60% complete. Petal dry weight increased linearly from hour -62
      (tight bud) to hour 10 (fully developed flower), then fell rapidly to hour 34 as
      senescence advanced. Increase in water content was proportional to dry weight
      increase from hour -62 to hour -14, but was more rapid as the bud cracked and the
      flower opened, giving an increase in fresh weight/dry weight ratio. Soluble
      carbohydrate was 50% of petal dry weight up to hour 10, then decreased during
      senescence to reach 4% by hour 34. Up until hour -14, fructan accounted for 80%
      of the soluble carbohydrate in the petals, whereas hexose accounted for only 2%.
      Fructan hydrolysis started just prior to bud crack at hour -14, reaching
      completion by hour 10 when no detectable fructan remained, and fructose plus
      glucose accounted for more than 80% of the total soluble carbohydrate. The
      proportion of sucrose remained constant throughout development. Osmolality of
      petal cell sap increased significantly during fructan hydrolysis, from 0.300 to
      0.340 osmolal. Cycloheximide applied to excised buds between hour -38 and hour 
      14 halted both fructan hydrolysis and flower expansion. The findings suggest that
      onset of fructan hydrolysis, with the concomitant large increase in osmoticum, is
      an important event driving flower expansion in daylily.

PMID- 12231929
TI  - Ethylene and Wound-Induced Gene Expression in the Preclimacteric Phase of
      Ripening Avocado Fruit and Mesocarp Discs.
AB  - Whereas intact postharvest avocado (Persea americana Mill.) fruit may take 1 or
      more weeks to ripen, ripening is hastened by pulsing fruit for 24 h with ethylene
      or propylene and is initiated promptly by cutting slices, or discs, of mesocarp
      tissue. Because the preclimacteric lag period constitutes the extended and
      variable component of the ripening syndrome, we postulated that selective gene
      expression during the lag period leads to the triggering of the climacteric.
      Accordingly, we sought to identify genes that are expressed gradually in the
      course of the lag period in intact fruit, are turned on sooner in response to a
      pulse, and are induced promptly in response to wounding (i.e. slicing). To this
      end, a mixed cDNA library was constructed from mRNA from untreated fruit, pulsed
      fruit, and aged slices, and the library was screened for genes induced by
      wounding or by pulsing and/or wounding. The time course of induction of genes
      encoding selected clones was established by probing northern blots of mRNA from
      tissues variously treated over a period of time. Four previously identified
      ripening-associated genes encoding cellulase, polygalacturonase (PG), cytochrome
      P-450 oxidase (P-450), and ethylene-forming enzyme (EFE, or 1-aminocyclopropane-1
      carboxylic acid synthase), respectively, were studied in the same way. Whereas
      cellulase, PG, and EFE were ruled out as having a role in the initiation of the
      climacteric, the time course of P-450 induction, as well as the response of same
      to pulsing and wounding met the criteria[mdash]together with several clones from
      the mixed library[mdash]for a gene potentially involved in preclimacteric events
      leading to the onset of the climacteric. Further, it was established that the
      continuous presence of ethylene is required for persisting induction, and it is
      suggested that in selected cases wounding may exert a synergistic effect on
      ethylene action.

PMID- 12231930
TI  - Two Isoforms of Dihydroxyacetone Phosphate Reductase from the Chloroplasts of
      Dunaliella tertiolecta.
AB  - Three isoforms of dihydroxyacetone phosphate reductase in extracts from
      Dunaliella tertiolecta have been separated by a diethylaminoethyl cellulose
      column chromatography with a shallow NaCl gradient. The chloroplasts contained
      the two major isoforms, and the third, minor form was in the cytosol. The
      isoforms are unstable in the absence of glycerol and they are cold labile, but
      they may be partially reactivated at 35[deg]C. The first chloroplast form to
      elute from the DEAE cellulose column was the major form when the cells were grown
      on high NaCl and it has been referred to as the form for glycerol production for
      osmoregulation or "osmoregulator form." The second form increased in specific
      activity when inorganic phosphate was increased in the growth media to stimulate
      growth, and it has been given the designation for the form for glyceride
      synthesis, "glyceride form." The osmoregulator form was stimulated by NaCl added
      to the enzyme assay, but not by reduced Escherichia coli thioredoxin. The
      glyceride form had properties similar to the enzyme in leaf chloroplast, such as
      inhibition by NaCl and by fatty acyl-coenzyme A derivatives and some stimulation
      by dithiothreitol, uridine diphosphate galactose, cyti-dine diphosphate
      dipalmatoyl diglyceride, and reduced E. coli thioredoxin. Thus, Dunaliella
      chloroplasts have a salt-stimulated osmoregulatory form of dihydroxyacetone
      phosphate reductase, which seems to have a role in glycerol production, and an
      isoform, which may be involved in glyceride synthesis and which has properties
      similar to the enzyme in chloroplasts of higher plants.

PMID- 12231931
TI  - Effect of Cations on Effective Permeability of Leaf Cuticles to Sulfuric Acid.
AB  - Many plants are exposed to prolonged episodes of anthropogenic acid precipitation
      with pH values of 4 or less, but there is little evidence of widespread direct
      damage to the plant cells. Acids appear to permeate leaf cuticle via charged
      pores, which act as a fixed buffer that delays but does not stop acid movement.
      We investigated the effect of cations on the movement of protons through
      astomatous isolated leaf cuticles of pear (Pyrus communis L.) and rough lemon
      (Citrus limon [L.] Burm. fils cv Ponderosa). Chloride salt solutions of Na, K,
      Ca, Cd, Mg, Gd, or Y in a diffusion apparatus were applied to the morphological
      inner surface of the cuticle, while the outer surface faced a large volume of pH
      3 or 4 sulfuric acid. Effective permeability was calculated from the change in
      the pH of the inner solution as measured with a pH microelectrode. Monovalent
      cations caused either no change (pear) or promotion (rough lemon) of proton
      movement. Divalent cations reduced proton movement in a concentration-dependent
      manner (both species), whereas trivalent cations (rough lemon only) caused the
      effective permeability to decrease to near zero. Inhibition by 10 mM CaCl2 was
      reversed with water. The effects of these cations on the permeability of cuticles
      to protons was used to elucidate mechanisms by which cations can protect leaves
      from acid precipitation in nature.

PMID- 12231932
TI  - Characterization of the Early Stages of Genetic Salt-Stress Responses in Salt
      Tolerant Lophopyrum elongatum, Salt-Sensitive Wheat, and Their Amphiploid.
AB  - Eleven unique cDNA clones corresponding to genes showing enhanced mRNA
      accumulation in the early stages of salt stress (early salt stress induced, ESI)
      were previously isolated. The accumulation of these mRNAs in Lophopyrum elongatum
      (Host) A. Love, salt-sensitive wheat (Triticum aestivum L.), and their amphiploid
      is compared. The accumulation of ESI mRNAs was much greater in the L. elongatum
      roots than in the shoots. Additionally, mRNA accumulation in the roots of the
      three genotypes showed a biphasic response. The first phase occurred within a few
      hours after the onset of stress and had a large osmotic shock component, as
      indicated by induction of the accumulation of these mRNAs by a nonsaline
      osmoticum. The ion-specific component, however, also played a role. External Ca2+
      reduced this response. The second phase was characterized by either constantly
      elevated mRNA levels or gradually increasing mRNA levels. The same biphasic
      response was elicited by exogenous abscisic acid (ABA). The response of all mRNAs
      to ABA closely approximated the response to 250 mM NaCl treatment in all three
      genotypes. The differences among the three genotypes in response to NaCl and ABA
      treatments were largely confined to the first phase of the response, in which
      mRNA levels were highest in L. elongatum and lowest in wheat. The levels of ESI
      mRNAs in the amphiploid closely approximated levels calculated on the basis of
      the doses of wheat and L. elongatum genomes in the amphiploid, which indicated an
      additive contribution of the genomes to early salt stress response in the
      amphiploid. The inducer of the ESI mRNA accumulation in response to NaCl and
      other osmotica is produced in the stressed roots and shows only minor, if any,
      translocation. A putative candidate for this inducer is root ABA.

PMID- 12231933
TI  - Chemical Signals from Avocado Surface Wax Trigger Germination and Appressorium
      Formation in Colletotrichum gloeosporioides.
AB  - The surface wax of the host, avocado (Persea americana) fruit, induced
      germination and appressorium formation in the spores of Colletotrichum
      gloeosporioides. Waxes from nonhost plants did not induce appressorium formation
      in this fungus, and avocado wax did not induce appressorium formation in most
      Colletotrichum species that infect other hosts. Bioassays of the thin-layer
      chromatographic fractions of the avocado wax showed that the fatty alcohol
      fraction was the main appressorium-inducing component. Testing of authentic n-C8
      to n-C32 fatty alcohols revealed that C24 and longer-chain alcohols induced
      appressorium formation. Gas-liquid chromatography/mass spectrometry analysis of
      free fatty alcohols revealed that avocado wax contains a high content of very
      long chains. Waxes from nonhost plants containing an even higher content of the
      very long-chain alcohols did not induce appressorium formation. Waxes from
      nonhost plants strongly inhibited appressorium induction by avocado wax. Thus, a
      favorable balance between appressorium-inducing very long-chain fatty alcohols
      and the absence of inhibitors allows the fungus to use the host surface wax to
      trigger germination and differentiation of infection structures in the pathogen.

PMID- 12231934
TI  - Role of Auxin in Maize Endosperm Development (Timing of Nuclear DNA
      Endoreduplication, Zein Expression, and Cytokinin).
AB  - The timing of developmental events and regulatory roles of auxin were examined in
      maize (Zea mays L.) endosperms. Zeatin, zeatin riboside, and indole-3-acetic acid
      (IAA) levels were determined by enzyme-linked immunosorbent (ELISA). Zeatin and
      zeatin riboside increased to maximal concentrations at an early stage (9 d after
      pollination [DAP]), corresponding to the stage when cell division rate was
      maximal. In contrast, IAA concentration was low at 9 DAP and abruptly increased
      from 9 to 11 DAP, thus creating a sharp decline in the cytokinin to auxin ratio.
      Coincident with the increase in IAA was an increase in DNA content per nucleus,
      attributed to postmitotic DNA replication via endoreduplication. Exogenous
      application of 2,4-dichlorophenoxyacetic acid (2,4-D) at 5 or 7 DAP hastened the
      time course of DNA accumulation per nucleus and increased the average nuclear
      diameter, whereas 2-(para-chlorophenoxy)isobutyric acid delayed such development.
      Exogenously applied 2,4-D hastened the accumulation of the zein polypeptides of
      apparent molecular masses of 12, 14, and 16 kD and the expression of mRNA
      hybridizing with a zein DNA probe. We conclude that an abrupt increase in auxin
      induces cellular differentiation events in endosperm, including endoredupliction
      and expression of particular zein storage proteins.

PMID- 12231935
TI  - Lack of Cross-Resistance of Imazaquin-Resistant Xanthium strumarium Acetolactate
      Synthase to Flumetsulam and Chlorimuron.
AB  - Acetolactate synthase (ALS) was isolated from a field population of cocklebur
      (Xanthium strumarium) that developed resistance to the herbicide Scepter
      following three consecutive years of application. The active ingredient of
      Scepter, imazaquin, gave an inhibitor concentration required to produce 50%
      inhibition of the enzyme activity that was more than 300 times greater for the
      resistant enzyme than for the wild-type cocklebur ALS. Tests with flumetsulam and
      chlorimuron show that the resistant ALS was not cross-resistant to these two
      other classes of ALS inhibitors.

PMID- 12231936
TI  - Activation of Cytosolic Pyruvate Kinase by Polyethylene Glycol.
AB  - Homogeneous cytosolic pyruvate kinase from endosperm of germinating castor oil
      (Ricinus communis L. cv Hale) seeds was potently activated by polyethylene
      glycol. The addition of 5% (w/v) polyethylene glycol to the pyruvate kinase
      reaction mixture caused a 2.6-fold increase in maximal velocity and 12.5- and 2
      fold reductions in Km values for phosphoenolpyruvate and ADP, respectively.
      Glycerol, ethylene glycol, and bovine serum albumin also enhanced pyruvate kinase
      activity, albeit to a lesser extent than polyethylene glycol. The addition of 5%
      (w/v) polyethylene glycol to the elution buffer during high-performance gel
      filtration chromatography of purified cytosolic pyruvate kinase helped to
      stabilize the active heterotetrameric native structure of the enzyme. A higher
      degree of inhibition by MgATP, but lower sensitivity to the inhibitors 3
      phosphoglycerate and fructose- 1,6-bisphosphate, was also observed in the
      presence of 5% (w/v) polyethylene glycol. It is concluded that (a) plant
      cytosolic pyruvate kinase activity and regulation, like that of other regulatory
      pyruvate kinases, is modified by extreme dilution in the assay medium, probably
      as a result of deaggregation of the native tetrameric enzyme, and (b) ATP is
      probably the major metabolic effector of germinating castor endosperm cytosolic
      pyruvate kinase in vivo.

PMID- 12231937
TI  - In Vitro Synthesis of Cellulose in Plants: Still a Long Way to Go!

PMID- 12231938
TI  - Pathway of Salicylic Acid Biosynthesis in Healthy and Virus-Inoculated Tobacco.
AB  - Salicylic acid (SA) is a likely endogenous regulator of localized and systemic
      disease resistance in plants. During the hypersensitive response of Nicotiana
      tabacum L. cv Xanthi-nc to tobacco mosaic virus (TMV), SA levels rise
      dramatically. We studied SA biosynthesis in healthy and TMV-inoculated tobacco by
      monitoring the levels of SA and its likely precursors in extracts of leaves and
      cell suspensions. In TMV-inoculated leaves, stimulation of SA accumulation is
      accompanied by a corresponding increase in the levels of benzoic acid. 14C-Tracer
      studies with cell suspensions and mock-or TMV-inoculated leaves indicate that the
      label moves from trans-cinnamic acid to SA via benzoic acid. In healthy and TMV
      inoculated tobacco leaves, benzoic acid induced SA accumulation. o-Coumaric acid,
      which was previously reported as a possible precursor of SA in other species, did
      not increase SA levels in tobacco. In healthy tobacco tissue, the specific
      activity of newly formed SA was equal to that of the supplied [14C]benzoic acid,
      whereas in TMV-inoculated leaves some isotope dilution was observed, presumably
      because of the increase in the pool of endogenous benzoic acid. We observed
      accumulation of pathogen-esis-related-1 proteins and increased resistance to TMV
      in benzoic acid- but not in o-coumaric acid-treated tobacco leaves. This is
      consistent with benzoic acid being the immediate precursor of SA. We conclude
      that in healthy and virus-inoculated tobacco, SA is formed from cinnamic acid via
      benzoic acid.

PMID- 12231939
TI  - Induction of Benzoic Acid 2-Hydroxylase in Virus-Inoculated Tobacco.
AB  - Salicylic acid (SA) plays an important role in the induction of plant resistance
      to pathogens. An accompanying article (N. Yalpani, J. Leon, M.A. Lawton, I.
      Raskin [1993] Plant Physiol 103: 315-321) shows that SA is synthesized via the
      decarboxylation of cinnamic acid to benzoic acid (BA), which is, in turn,
      hydroxylated to SA. Leaf extracts of tobacco (Nicotiana tabacum L. cv Xanthi-nc)
      catalyze the 2-hydroxylation of BA to SA. The monooxygenase catalyzing this
      reaction, benzoic acid 2-hydroxylase (BA2H), required NAD(P)H or reduced methyl
      viologen as an electron donor. BA2H activity was detected in healthy tobacco leaf
      extracts (1-2 nmol h-1 g-1 fresh weight) and was significantly increased upon
      inoculation with tobacco mosaic virus (TMV). This increase paralleled the levels
      of free SA in the leaves. Induction of BA2H activity was restricted to tissue
      expressing a hypersensitive response at 24[deg]C. TMV induction of BA2H activity
      and SA accumulation were inhibited when inoculated tobacco plants were incubated
      at 32[deg]C. However, when inoculated plants were incubated for 4 d at 32[deg]C
      and then transferred to 24[deg]C, they showed a 15-fold increase in BA2H activity
      and a 65-fold increase in free SA content compared with healthy plants incubated
      at 24[deg]C. Treatment of leaf tissue with the protein synthesis inhibitor
      cycloheximide blocked the induction of BA2H activity by TMV. The effect of TMV
      inoculation on BA2H could be duplicated by infiltrating leaf discs of healthy
      plants with BA. This response was observed even when applied levels of BA were
      much lower than the levels observed in vivo after virus inoculation. Feeding
      tobacco leaves with phenylalanine, cinnamic acid, or o-coumaric acid (putative
      precursors of SA) failed to trigger the induction of BA2H activity. BA2H appears
      to be a pathogen-inducible protein with an important regulatory role in SA
      accumulation during the development of induced resistance to TMV in tobacco.

PMID- 12231940
TI  - Biochemical Basis of Resistance of Tobacco Callus Tissue Cultures to
      Hydroxyphenylethylamines.
AB  - It has been reported that hydroxyphenylethylamines, such as tyramine and
      octopamine, are toxic to tobacco (Nicotiana tabacum L.) callus cultures grown in
      the presence of auxins, whereas calli grown in the presence of cytokinins and
      crown gall cultures are resistant to these amines (P. Christou and K.A. Barton
      [1989] Plant Physiol 89: 564-568). In an attempt to understand the underlying
      mechanism of this resistance, we compared the fates of tyramine in tyramine
      sensitive and tyramine-resistant tobacco tissue cultures (cv Xanthi nc). The very
      rapid formation of black-colored oxidation products from tyramine in sensitive
      tissues suggested that the toxicity might be caused by the oxidation of tyramine
      by phenol oxidases present in the tissues or released into the medium after
      subculture. This was confirmed through many indirect procedures (effect of
      exogenously added tyrosinase, induction of polyphenol oxidase [PPO] activity by
      auxin, etc.). The study of tyramine structure-activity relationships further
      suggested that the toxicity of tyramine might be due to the formation of
      indolequinones after oxidation by PPO. Subculture of calli grown on 2,4
      dichlorophenoxyacetic acid in a medium containing benzyladenine triggered a slow
      decrease in PPO activity and dramatic increases in peroxidase and tyramine
      hydroxycinnamoyl transferase (THT) activities. THT was undetectable in calli
      grown on 2,4-dichlorophenoxyacetic acid but very active in tyramine-resistant
      crown gall cultures. Moreover, when [3H]tyramine was fed in vivo to tyramine
      resistant tissues, it was rapidly integrated into cell walls in the wound
      periderm formed at the periphery of the calli. Both the conjugation of tyramine
      and its integration into cell walls could compete with the formation of toxic
      quinones and therefore play a part in the resistance. Thus, it seems likely that
      the control of the toxicity of hydroxyphenylethylamines by cytokinins results
      primarily from changes in the metabolism and the compartmentation of these
      amines.

PMID- 12231941
TI  - Transport of Water and Solutes across Maize Roots Modified by Puncturing the
      Endodermis (Further Evidence for the Composite Transport Model of the Root).
AB  - The effects of puncturing the endodermis of young maize roots (Zea mays L.) on
      their transport properties were measured using the root pressure probe. Small
      holes with a diameter of 18 to 60 [mu]m were created 70 to 90 mm from the tips of
      the roots by pushing fine glass tubes radially into them. Such wounds injured
      about 10-2 to 10-3% of the total surface area of the endodermis, which, in these
      hydroponically grown roots, had developed a Casparian band but no suberin
      lamellae. The small injury to the endodermis caused the original root pressure,
      which varied from 0.08 to 0.19 MPa, to decrease rapidly (half-time = 10-100 s)
      and substantially to a new steady-state value between 0.02 and 0.07 MPa. The
      radial hydraulic conductivity (Lpr) of control (uninjured) roots determined using
      hydrostatic pressure gradients as driving forces was larger by a factor of 10
      than that determined using osmotic gradients (averages: Lpr [hydrostatic] = 2.7 x
      10-7 m s-1 MPa-1; Lpr [osmotic] = 2.2 x 10-8 m s-1 MPa-1; osmotic solute: NaCl).
      Puncturing the endodermis did not result in measurable increases in hydraulic
      conductivities measured by either method. Thus, the endodermis was not rate
      limiting root Lpr: apparently the hydraulic resistance of roots was more evenly
      distributed over the entire root tissue. However, puncturing the endodermis did
      substantially change the reflection ([sigma]sr) and permeability (Psr)
      coefficients of roots for NaCl, indicating that the endodermis represented a
      considerable barrier to the flow of nutrient ions. Values of [sigma]sr decreased
      from 0.64 to 0.41 (average) and Psr increased by a factor of 2.6, i.e. from 3.8 x
      10-9 to 10.1 x 10.-9 m s-1(average). The roots recovered from puncturing after a
      time and regained root pressure. Measurable increases in root pressure became
      apparent as soon as 0.5 to 1 h after puncturing, and original or higher root
      pressures were attained 1.5 to 20 h after injury. However, after recovery roots
      often did not maintain a stable root pressure, and no further osmotic experiments
      could be performed with them. The Casparian band of the endodermis is
      discontinuous at the root tip, where the endodermis has not yet matured, and at
      sites of developing lateral roots. Measurements of the cross-sectional area of
      the apoplasmic bypass at the root tip yielded an area of 0.031% of the total
      surface area of the endodermis. An additional 0.049% was associated with lateral
      root primordia. These areas are larger than the artificial bypasses created by
      wounding in this study and may provide pathways for a "natural bypass flow" of
      water and solutes across the intact root. If there were such a pathway, either in
      these areas or across the Casparian band itself, roots would have to be treated
      as a system composed of two parallel pathways (a cell-to-cell and an apoplasmic
      path). It is demonstrated that this "composite transport model of the root"
      allows integration of several transport properties of roots that are otherwise
      difficult to understand, namely (a) the differences between osmotic and
      hydrostatic water flow, (b) the dependence of root hydraulic resistance on the
      driving force or water flow across the root, and (c) low reflection coefficients
      of roots.

PMID- 12231942
TI  - Determination of Auxin-Dependent pH Changes in Coleoptile Cell Walls by a Null
      Point Method.
AB  - The present debate on the validity of the "acid-growth theory" of auxin (indole-3
      acetic acid, IAA) action concentrates on the question of whether IAA-induced
      proton excretion into the cell wall is quantitatively sufficient to provide the
      shift in pH that is required to explain IAA-induced growth (see D.L. Rayle, R.E.
      Cleland [1992] Plant Physiol 99:1271-1274 for a recent apologetic review of the
      acid-growth theory). In the present paper a null-point method has been employed
      for determining the growth-effective cell-wall pH in the presence and absence of
      IAA after 60 min of treatment. Elongation of abraded maize (Zea mays L.) and oat
      (Avena sativa L.) coleoptile segments was measured with the high resolution of a
      displacement transducer. The abrasion method employed for rendering the outer
      epidermal cell wall permeable for buffer ions was checked with a dye-uptake
      method. Evidence is provided demonstrating that externally applied solutes
      rapidly and homogeneously penetrate into the epidermal wall, whereas penetration
      into the inner tissue walls is strongly retarded. "Titration" curves of IAA
      induced and basal elongation were determined by measuring the
      promoting/inhibiting effect of medium pH under iso-osmotic conditions in the
      range of pH 4.5 to 6.0. In maize, the null point (no pH-dependent change in
      elongation rate after 5-10 min of treatment with 10 mmol L-1 citrate buffer) was
      pH 5.00 after 60 min of IAA-induced growth, and the null-point pH determined
      similarly in IAA-depleted tissue (10 times smaller elongation rate) was 5.25.
      Corresponding titration curves with Avena segments led to slightly lower null
      point pH values both in the presence and absence of IAA-induced growth. After
      induction of acid-mediated extension by 1 [mu]mol L-1 fusicoccin (FC) in maize,
      the null-point pH shifted to 3.9. At 0.5 [mu]mol L-1, FC induced the same
      elongation rate as IAA but a 9-fold larger rate of proton excretion. At 0.033
      [mu]mol L-1, FC induced the same rate of proton excretion as IAA but had no
      appreciable effect on elongation. The implications of these results against the
      background of recent attempts to revitalize the acid-growth theory of IAA action
      are discussed.

PMID- 12231943
TI  - Alteration of [beta]-Tubulin Gene Expression during Low-Temperature Exposure in
      Leaves of Arabidopsis thaliana.
AB  - Responses of [beta]-tubulin gene expression to low-temperature exposure (4[deg]C)
      have been investigated in leaves of Arabidopsis thaliana. During low-temperature
      exposure, the patterns of both [alpha]- and [beta]-tubulin isoforms are altered;
      the effect is smaller for the [alpha]-tubulins than for the [beta]-tubulins,
      however. An examination of [beta]-tubulin gene expression revealed that during
      low-temperature exposure, transcript levels of TUB2, TUB3, TUB6, and TUB8
      decrease, whereas those of TUB4, TUB5, and TUB7 remain constant, and the TUB9
      transcript level increases. The changes in transcript levels of TUB6, TUB8, and
      TUB9 were detectable after 6 h of low-temperature treatment. As shown by
      transcription-blocking experiments, the in vivo decay rates at 25[deg]C are
      comparable to those at 4[deg]C for TUB5, TUB6, and TUB8 mRNAs, whereas TUB9 mRNA
      appears to be more stable at 4[deg]C than at 25[deg]C. Thus, decreases in
      transcript levels of TUB6 and TUB8 in response to low temperature appear to be
      regulated at the transcriptional level, and the increase in TUB9 transcript level
      that results from lowering the temperature from 25[deg]C to 4[deg]C may be due in
      part to its slower rate of decay at 4[deg]C. When a chimeric gene containing 1061
      base pairs of TUB8 5[prime] flanking DNA fused to the [beta]-glucuronidase coding
      region was used to produce transgenic Arabidopsis plants, the chimeric gene
      expression was down-regulated in response to low temperature as assayed by
      histochemical localization and RNA gel blots. These results confirm that the
      alteration of transcript levels of TUB8 in response to low temperature is
      regulated at the transcriptional level.

PMID- 12231944
TI  - Proteolysis during Development and Senescence of Effective and Plant Gene
      Controlled Ineffective Alfalfa Nodules.
AB  - Plant-controlled ineffective root nodules, conditioned by the in1 gene in
      Medicago sativa L. cv Saranac, undergo premature senescence and have reduced
      levels of many late nodulins. To ascertain which factors contribute to premature
      senescence, we have evaluated proteolysis as it occurs throughout the development
      of ineffective Saranac (in1Sa) and effective Saranac nodules. Cysteine protease
      activities with acidic pH optimum and enzyme proteins were present in both
      genotypes. We found that acidic protease activity was low in effective Saranac
      nodules throughout their development. In contrast, by 2 weeks after inoculation,
      acid protease activity of in1Sa nodules was severalfold higher than that of
      Saranac nodules and remained high until the experiment was terminated 8 weeks
      later. This increase in protease enzyme activity correlated with an increase in
      protease protein amounts. Increased protease activity and amount in in1Sa nodules
      was correlated with a decrease in nodule soluble protein. The time at which in1Sa
      nodules initially showed increased protease activity corresponded to when
      symbiosis deteriorated. High levels of phosphoenolpyruvate carboxylase (PEPC)
      protein were expressed in effective nodules by 12 d after inoculation and
      expression was associated with low proteolytic enzyme activity. In contrast,
      although PEPC was expressed in in1Sa nodules, PEPC protein was not found 12 d
      after inoculation and thereafter. Acidic protease from in1Sa nodules could also
      degrade purified leghemoglobin. These data indicate that premature senescence and
      low levels of late nodulins in in1Sa nodules can be correlated in part with
      increased proteolysis.

PMID- 12231945
TI  - Controlled Proteolysis Activates the Plasma Membrane Ca2+ Pump of Higher Plants
      (A Comparison with the Effect of Calmodulin in Plasma Membrane from Radish
      Seedlings).
AB  - The effects of calmodulin and of controlled trypsin treatments on the activity of
      the Ca2+ pump were investigated in plasma membrane purified from radish (Raphanus
      sativus L.) seedlings. Treatment of the plasma membrane with ethylenediaminetetra
      acetate (EDTA), which removed about two-thirds of the plasma membrane-associated
      calmodulin, markedly increased the stimulation of the Ca2+ pump by calmodulin. In
      EDTA-treated plasma membrane, stimulation by calmodulin of the Ca2+ pump activity
      was maximal at low free Ca2+ (2-5 [mu]M) and decreased with the increase of free
      Ca2+ concentration. The Ca2+ pump activity was stimulated also by a controlled
      treatment of the plasma membrane with trypsin: the effect of trypsin treatment
      depended on the concentration of both trypsin and plasma membrane proteins and on
      the duration of incubation. Stimulation of the Ca2+ pump activity by trypsin
      treatment of the plasma membrane was similar to that induced by calmodulin both
      in extent and in dependence on the free Ca2+ concentration in the assay medium.
      Moreover, the Ca2+ pump of trypsin-treated plasma membrane was insensitive to
      further stimulation by calmodulin, suggesting that limited proteolysis
      preferentially cleaves a regulatory domain of the enzyme that is involved in its
      activation by calmodulin.

PMID- 12231946
TI  - Controlled Proteolysis Mimics the Effect of Fusicoccin on the Plasma Membrane H+
      ATPase.
AB  - We analyzed the effects of controlled treatments with trypsin of plasma membrane
      (PM) isolated from radish (Raphanus sativus L.) seedlings on the activity of the
      PM H+-ATPase, and we compared them with those of fusicoccin (FC). Mild treatments
      of the PM with trypsin, which led to a decrease of the molecular mass of the
      peptide of about 10 kD, markedly increased the H+-ATPase activity. The effect
      strongly increased with the increase of pH of the assay medium from 6.1 to 7.5,
      so the pH optimum of the enzyme activity shifted from 6.8 in untreated PM to 7.1
      in trypsin-treated PM. The proteolytic treatment activated only the portion of PM
      H+-ATPase activity that is stable to preincubation in assay medium in the absence
      of ATP and determined a strong increase of Vmax and a less marked decrease of the
      apparent Km for Mg-ATP. All of these effects were very similar to those
      determined by FC, which activated the PM H+-ATPase without promoting its
      proteolytic cleavage. FC did not further activate the H+-ATPase activity of
      trypsin-treated PM under conditions in which the FC receptor was protected from
      the attack of trypsin. Conversely, trypsin treatment had little effect on the PM
      H+-ATPase preactivated with FC. Moreover, the activity of the PM H+-ATPase
      preactivated with FC was not further activated by Iysolecithin. These results
      indicate that the modification of the PM H+-ATPase of higher plants triggered by
      the FC-receptor complex hinders the inhibitory interaction of the regulatory C
      terminal domain with the active site.

PMID- 12231947
TI  - Circadian Rhythms in Stomatal Responsiveness to Red and Blue Light.
AB  - Stomata of many plants have circadian rhythms in responsiveness to environmental
      cues as well as circadian rhythms in aperture. Stomatal responses to red light
      and blue light are mediated by photosynthetic photoreceptors; responses to blue
      light are additionally controlled by a specific blue-light photoreceptor. This
      paper describes circadian rhythmic aspects of stomatal responsiveness to red and
      blue light in Vicia faba. Plants were exposed to a repeated light:dark regime of
      1.5:2.5 h for a total of 48 h, and because the plants could not entrain to this
      short light:dark cycle, circadian rhythms were able to "free run" as if in
      continuous light. The rhythm in the stomatal conductance established during the
      1.5-h light periods was caused both by a rhythm in sensitivity to light and by a
      rhythm in the stomatal conductance established during the preceding 2.5-h dark
      periods. Both rhythms peaked during the middle of the subjective day. Although
      the stomatal response to blue light is greater than the response to red light at
      all times of day, there was no discernible difference in period, phase, or
      amplitude of the rhythm in sensitivity to the two light qualities. We observed no
      circadian rhythmicity in net carbon assimilation with the 1.5:2.5 h light regime
      for either red or blue light. In continuous white light, small rhythmic changes
      in photosynthetic assimilation were observed, but at relatively high light
      levels, and these appeared to be attributable largely to changes in internal CO2
      availability governed by stomatal conductance.

PMID- 12231948
TI  - Elicitor-Induced Changes in Ca2+ Influx, K+ Efflux, and 4-Hydroxybenzoic Acid
      Synthesis in Protoplasts of Daucus carota L.
AB  - Suspension-cultured carrot cells (Daucus carota) and their protoplasts respond to
      a fungal elicitor prepared from the culture medium of Pythium aphanidermatum by
      accumulating 4-hydroxybenzoic acid (4-HBA). Protoplasts release the compound into
      the culture medium. Using 45CaCl2 as a tracer, we were able to demonstrate that
      the secretion of 4-HBA is preceded by a rapid increase in the Ca2+ influx and a
      concomitant K+ efflux. If the increased Ca2+ influx was prevented by
      ethyleneglycol-bis([beta]-aminoethylether)-N,N[prime]-tetraacetic acid, 4-HBA
      synthesis was inhibited by 70%. These results are discussed with regard to signal
      transduction from the plasma membrane to the nucleus of carrot protoplasts.

PMID- 12231949
TI  - Protein Kinases in Zucchini (Characterization of Calcium-Requiring Plasma
      Membrane Kinases).
AB  - Using an in situ phosphorylation assay with zucchini (Cucurbita pepo L. cv Dark
      Green) seedling tissue, we have identified numerous polypeptides that are capable
      of acting as protein kinases. Total protein preparations from different organs
      contain different kinase profiles, but all are within the range of 55 to 70 kD.
      At least four kinases are associated with highly purified plasma membranes from
      etiolated zucchini hypocotyls. The major phosphorylated polypeptides from plasma
      membranes range in apparent molecular mass from 58 to 68 kD. The plasma membrane
      kinases are activated by micromolar concentrations of calcium and phosphorylate
      serine, and, to a lesser extent, threonine residues. These characteristics are
      similar to those of a soluble calcium-dependent protein kinase that has been
      purified to homogeneity from soybean suspension cultures. Three of the zucchini
      plasma membrane kinases share antigenic epitopes with the soluble soybean kinase.
      The presence of kinase activity at different apparent molecular masses may be
      indicative of separate kinases with similar characteristics. The zucchini
      hypocotyl protein kinases are not removed from plasma membrane vesicles by 0.5 M
      NaCl/5 mM ethylenediaminetetraacetate or by detergent concentrations below the
      critical micelle concentration of two types of detergent. This indicates that the
      plasma membrane protein kinases are tightly associated with the membrane in
      zucchini seedlings.

PMID- 12231950
TI  - A Model of the Regulation of Nitrogenase Electron Allocation in Legume Nodules
      (I. The Diffusion Barrier and H2 Inhibition of N2 Fixation).
AB  - A mathematical model is presented to explain the regulation of nitrogenase
      electron allocation to N2 fixation (EAC) in legume nodules. The model is based on
      two assumptions: (a) that H2 inhibits N2 fixation in a competitive manner; and
      (b) that O2, H2, and N2 move into and out of nodules by diffusion and their
      movement is impeded by a diffusion barrier, the permeability of which is
      controlled to maintain a very low infected cell O2 concentration. When the model
      was used to simulate nodules displaying a range of values for total nitrogenase
      activity (TNA), maximum EAC values were predicted to be between 0.69 and 0.71,
      and a negative correlation was predicted to exist between EAC and TNA. These
      predictions were in good agreement with empirically derived values reported in
      the literature and support the suggestion that H2 inhibition of N2 fixation is a
      major determinant in the regulation of nitrogenase EAC in legume nodules. Two
      versions of the model were constructed. A closed-pore model assumed that the
      diffusion barrier consisted of a solid shell of water of variable thickness in
      the nodule cortex. An open-pore model assumed that a small number of gas-filled
      intercellular spaces connected the nodule central zone with the root atmosphere
      and these pores were opened or closed by water to provide variations in the
      nodule's permeability to gas diffusion. Because of differences in the diffusivity
      of gases in the gaseous and aqueous phases, the model predicted that, at a given
      infected cell O2 concentration, an open-pore diffusion barrier would result in
      less H2 accumulation in the infected cells than a closed-pore diffusion barrier.
      Therefore, the model may be used to test specific hypotheses about the physical
      structure of the barrier to gas diffusion in legume nodules.

PMID- 12231951
TI  - Cell Wall Metabolism in Ripening Fruit (VI. Effect of the Antisense
      Polygalacturonase Gene on Cell Wall Changes Accompanying Ripening in Transgenic
      Tomatoes).
AB  - Cell walls of tomato (Lycopersicon esculentum Mill.) fruit, prepared so as to
      minimize residual hydrolytic activity and autolysis, exhibit increasing
      solubilization of pectins as ripening proceeds, and this process is not evident
      in fruit from transgenic plants with the antisense gene for polygalacturonase
      (PG). A comparison of activities of a number of possible cell wall hydrolases
      indicated that antisense fruit differ from control fruit specifically in their
      low PG activity. The composition of cell wall fractions of mature green fruit
      from transgenic and control (wild-type) plants were indistinguishable except for
      trans-1,2-diaminocyclohexane-N,N,N[prime],N[prime]-tetraacetic acid (CDTA)
      soluble pectins of transgenic fruit, which had elevated levels of arabinose and
      galactose. Neutral polysaccharides and polyuronides increased in the water
      soluble fraction of wild-type fruit during ripening, and this was matched by a
      decline in Na2CO3-soluble pectins, equal in magnitude and timing. This, together
      with compositional analysis showing increasing galactose, arabinose, and rhamnose
      in the water-soluble fraction, mirrored by a decline of these same residues in
      the Na2CO3-soluble pectins, suggests that the polyuronides and neutral
      polysaccharides solubilized by PG come from the Na2CO3-soluble fraction of the
      tomato cell wall. In addition to the loss of galactose from the cell wall as a
      result of PG activity, both antisense and control fruit exhibit an independent
      decline in galactose in both the CDTA-soluble and Na2CO3-soluble fractions, which
      may play a role in fruit softening.

PMID- 12231952
TI  - Comparative Studies on Ferredoxin-NADP+ Oxidoreductase Isoenzymes Derived from
      Different Organs by Antibodies Specific for the Radish Root- and Leaf-Enzymes.
AB  - Determination of the prosthetic group and titration of sulfhydryl group of
      ferredoxin-NADP+ oxidoreductase (FNR) from roots of radish (Raphanus sativus var
      acanthiformis cv Miyashige) confirmed its similarity to leaf-FNR. Antisera
      directed against radish root-FNR and leaf-FNR distinguished the enzyme forms from
      roots and leaves of radish as well as other flowering plants. The FNR isoenzymes
      showed organ-specific distributions. In horsetail (Equisetum arvense L.) and
      cultured liverwort cells (Marchantia polymorpha), at least two FNR isoenzymes
      were distinguished by the antisera. FNR from Chlorella vulgaris reacted only with
      the anti-root-FNR antiserum. FNR from a cyanobacterium, Spirulina spp., failed to
      react with either antiserum.

PMID- 12231953
TI  - Evidence for a Single Naphthylphthalamic Acid Binding Site on the Zucchini Plasma
      Membrane.
AB  - The binding of [2,3,4,5,(n)-3H]N-1-napthylphthalamicacid ([3H]-NPA) to zucchini
      (Cucurbita pepo L.) plasma membranes was examined in detail using two different
      filtration assays and the results were rigorously analyzed by saturation curves,
      double-reciprocal plots, Scatchard plots, Hill plots, and the computer program
      Ligand (P.J. Munson, D. Rodbard [1980] Anal Biochem 107: 220-239). To facilitate
      these analyses, a new assay that allows rapid and quantitative analysis of
      [3H]NPA binding with high reproducibility and ease of manipulation has been
      developed. These detailed kinetic analyses indicate that only one binding site
      for [3H]NPA (Kd = 16 nM) was associated with the zucchini plasma membrane.
      Analysis of [3H]NPA dissociation by several auxin transport inhibitors revealed
      similar dissociation constants with both plasma and microsomal membrane.
      Collectively, these data indicate the presence of only one binding site for NPA
      associated with the zucchini plasma membrane.

PMID- 12231954
TI  - Expression and Accumulation Patterns of Nitrogen-Responsive Lipoxygenase in
      Soybeans.
AB  - Gene expression and protein accumulation patterns of nitrogen-responsive
      lipoxygenase (LOX-NR), as a representative vegetative storage protein, were
      investigated in nonnodulated soybeans (Glycine max [L.] Merr. cv Wye). The form
      of available nitrogen (supplied as NH4NO3, NH4+, NO3-, or urea) influenced the
      mRNA level and the amount of LOX protein, indicating that preferential
      accumulation of LOX may occur. Soybeans were grown with 0, 2, 5, and 16 mM total
      nitrogen to determine the extent to which LOX accumulation responded to soil
      nitrogen levels. Analysis of both mRNA and protein levels was conducted in shoot
      tips, stems, pod walls, and leaves over the entire life cycle of the plant. A
      general correlation between increasing available nitrogen level and LOX level was
      seen in the shoot tip and other organs throughout the soybean life cycle.
      However, appreciable amounts of LOX-NR mRNA and protein accumulated even when
      plants were grown under conditions of nitrogen deficiency. The results indicate
      that LOX may play an important role as a temporary storage site for amino acids
      in the developing shoot tip. The expression patterns of LOX-NR in plants grown
      under nitrogen deficiency suggest that these proteins, although responsive to
      nitrogen status, may not function solely as temporary storage pools for amino
      acids.

PMID- 12231955
TI  - Purification and Characterization of Catalase from Loblolly Pine (Pinus taeda L.)
      Megagametophytes.
AB  - Catalase (EC 1.11.1.6) was purified to near homogeneity from isolated
      megagametophytes of germinated loblolly pine (Pinus taeda L.) seeds, and
      monospecific antibodies were elicited in rabbits. Following a procedure that
      involved acetone extraction, (NH4)2SO4 fractionation, and four chromatographic
      steps (i.e. DE-52 cellulose, Superdex-200, hydroxylapatite, and phenyl-Sepharose
      CL-4B), catalase was purified about 140-fold to a final specific activity of 2215
      mmol min-1 mg-1 of protein. Cotton isocitrate lyase antibodies were used, and
      protein immunoblots revealed that the resolution on hydroxylapatite and phenyl
      Sepharose allowed for the complete separation of catalase from contaminating
      isocitrate lyase. The molecular masses of the native enzyme and its subunit are
      235 and 59 kD, respectively, indicating that the pine holoenzyme is a
      homotetramer. Loblolly pine catalase exists as multiple isoforms. When
      megagametophytes taken 7 d after imbibition at 30[deg]C were extracted, subjected
      to nondenaturing isoelectric focusing, and stained for catalase activity, at
      least four catalase isoforms were observed, including one dominant form with an
      isoelectric point of 6.87. Purified pine catalase is not a glycoprotein and has a
      ratio of absorbance at 208 nm to absorbance at 405 nm of 1.5. When probed with
      loblolly pine catalase antibodies, protein blots of cell-free extracts from
      megagametophytes of mature, stratified, and germinated loblolly pine seeds, the
      megagametophyte glyoxysomal fraction, and purified loblolly pine catalase all
      revealed one immunoreactive 59-kD polypeptide. This indicates that no detectable
      change in the enzyme's monomeric molecular mass occurs during seed stratification
      and germination, early seedling growth, and purification.

PMID- 12231956
TI  - Floridoside, L-Isofloridoside, and D-Isofloridoside in the Red Alga Porphyra
      columbina (Seasonal and Osmotic Effects).
AB  - The quantitative heteroside distribution in Porphyra columbina Montagne and
      Bangia atropurpurea (Roth) C. Agardh (Bangiales, Rhodophyta) has been measured
      using 13C-nuclear magnetic resonance spectroscopy and gas-liquid chromatography.
      In P. columbina, floridoside and both D- and L-isofloridoside were recorded, with
      concentrations of L-isofloridoside exceeding those of floridoside. All three
      compounds were also measured in B. atropurpurea. Marked changes in the relative
      amounts of the heterosides were recorded throughout the season. The role of L
      isofloridoside in the osmotic acclimation of P. columbina has been demonstrated.

PMID- 12231957
TI  - Transpiration Induces Radial Turgor Pressure Gradients in Wheat and Maize Roots.
AB  - Previous studies have shown both the presence and the absence of radial turgor
      and osmotic pressure gradients across the cortex of roots. In this work,
      gradients were sought in the roots of wheat (Triticum aestivum) and maize (Zea
      mays) under conditions in which transpiration flux across the root was varied
      This was done by altering the relative humidity above the plant, by excising the
      root, or by using plants in which the leaves were too young to transpire. Roots
      of different ages (4-65 d) were studied and radial profiles at different
      distances from the tip (5-30 mm) were measured. In both species, gradients of
      turgor and osmotic pressure (increasing inward) were found under transpiring
      conditions but not when transpiration was inhibited. The presence of radial
      turgor and osmotic pressure gradients, and the behavior of the gradient when
      transpiration is interrupted, indicate that active membrane transport or radial
      solvent drag may play an important role in the distribution of solutes across the
      root cortex in transpiring plants. Contrary to the conventional view, the flow of
      water and solutes across the symplastic pathway through the plasmodesmata cannot
      be inwardly directed under transpiring conditions.

PMID- 12231958
TI  - CO2 Exchange and Growth of the Crassulacean Acid Metabolism Plant Opuntia ficus
      indica under Elevated CO2 in Open-Top Chambers.
AB  - CO2 uptake, water vapor conductance, and biomass production of Opuntia ficus
      indica, a Crassulacean acid metabolism species, were studied at CO2
      concentrations of 370, 520, and 720 [mu]L L-1 in open-top chambers during a 23
      week period. Nine weeks after planting, daily net CO2 uptake for basal cladodes
      at 520 and 720 [mu]L L-1 of CO2 was 76 and 98% higher, respectively, than at 370
      [mu]L L-1. Eight weeks after daughter cladodes emerged, their daily net CO2
      uptake was 35 and 49% higher at 520 and 720 [mu]L L-1 of C02, respectively, than
      at 370 [mu]L L-1. Daily water-use efficiency was 88% higher under elevated CO2
      for basal cladodes and 57% higher for daughter cladodes. The daily net CO2 uptake
      capacity for basal cladodes increased for 4 weeks after planting and then
      remained fairly constant, whereas for daughter cladodes, it increased with
      cladode age, became maximal at 8 to 14 weeks, and then declined. The percentage
      enhancement in daily net CO2 uptake caused by elevated CO2 was greatest initially
      for basal cladodes and at 8 to 14 weeks for daughter cladodes. The chlorophyll
      content per unit fresh weight of chlorenchyma for daughter cladodes at 8 weeks
      was 19 and 62% lower in 520 and 720 [mu]L L-1 of CO2, respectively, compared with
      370 [mu]L L-1. Despite the reduced chlorophyll content, plant biomass production
      during 23 weeks in 520 and 720 [mu]L L-1 of CO2 was 21 and 55% higher,
      respectively, than at 370 [mu]L L-1. The root dry weight nearly tripled as the
      C02 concentration was doubled, causing the root/shoot ratio to increase with CO2
      concentration. During the 23-week period, elevated CO2 significantly increased
      CO2 uptake and biomass production of O. ficus-indica.

PMID- 12231959
TI  - Seasonal Variations in Rubber Biosynthesis, 3-Hydroxy-3-Methylglutaryl-Coenzyme A
      Reductase, and Rubber Transferase Activities in Parthenium argentatum in the
      Chihuahuan Desert.
AB  - The rubber content and the activities of enzymes in the polyisoprenoid pathway in
      Parthenium argentatum (guayule) were examined throughout the growing season in
      field plots in the Chihuahuan Desert. The rubber content of the plants was low in
      July and August and slowly increased until October. From October to December
      there was a rapid increase in rubber formation (per plant) from 589.0 mg to
      4438.0 mg. The percentage of rubber in the plants increased from 0.7% (mg/g dry
      weight) in August and 1.27% in October to 5.5% in December. The rapid increase in
      rubber formation may result from exposing the plants to low temperatures of 5 to
      7[deg]C. The activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) was 21.1
      nmol mevalonic acid (MVA) h-1 g-1 fresh weight in the bark of the lower stems in
      June during seedling growth and decreased to 5.1 nmol MVA h-1g-1 fresh weight in
      July and 2.9 nmol MVA h-1 g-1 fresh weight in September. From October to
      December, the activity increased from 5.0 to 29.9 nmol MVA h-1 g-1 fresh weight.
      The activity of rubber transferase was 65.5 nmol isopentenyl pyrophosphate (IPP)
      h-1 g-1fresh weight in the bark in September and increased to 357.5 nmol IPP h-1
      g-1 fresh weight in December. The rapid increase in the activities of HMGR and
      rubber transferase coincided with the rapid increase in rubber formation. The
      activities of MVA kinase and IPP isomerase did not significantly increase in the
      fall and winter. A tomato HMGR-1 cDNA probe containing a highly conserved C
      terminal region of HMGR genes hybridized at low stringency with several bands on
      blots of HindIII-digested genomic DNA from guayule. In northern blots with the
      HMGR-1 cDNA probe at low stringency, HMGR mRNA was high in June and November,
      corresponding to periods of high HMGR activity during seedling growth and rapid
      increase in rubber formation. The seasonal variations in rubber formation and
      HMGR mRNA, HMGR activity, and rubber transferase activity may be due to low
      temperature stimulation in the fall and winter months.

PMID- 12231960
TI  - Calcium Levels Affect the Ability to Immunolocalize Calmodulin to Cortical
      Microtubules.
AB  - Calcium affects the stability of cortical microtubules (MTs) in lysed
      protoplasts. This calmodulin (CaM)-mediated interaction may provide a mechanism
      that serves to integrate cellular behavior with MT function. To test the
      hypothesis that CaM associates with these MTs, monoclonal antibodies were
      produced against CaM, and one (designated mAb1D10) was selected for its
      suitability as an immunocytochemical reagent. It is shown that CaM associates
      with the cortical MTs of cultured carrot (Daucus carota L.) and tobacco
      (Nicotiana tabacum L.) cells. Inasmuch as CaM interacts with calcium and affects
      the behavior of these MTs, we hypothesized that calcium would alter this
      association. To test this, protoplasts containing taxol-stabilized MTs were lysed
      in the presence of various concentrations of calcium and examined for the
      association of CaM with cortical MTs. At 1 [mu]M calcium, many protoplasts did
      not have CaM in association with the cortical MTs, whereas at 3.6 [mu]M calcium,
      this association was completely abolished. Control experiments were performed to
      eliminate alternate explanations including differential antibody binding in the
      presence of calcium and/or taxol, detergent-induced redistribution of antigen,
      and epitope masking. The results are discussed in terms of a model in which CaM
      associates with MTs via two types of interactions, one that occurs in the
      presence of calcium and another that occurs only in its absence.

PMID- 12231961
TI  - Differential Involvement of the Circadian Clock in the Expression of Genes
      Required for Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase Synthesis, Assembly,
      and Activation in Arabidopsis thaliana.
AB  - We have investigated the role of the circadian clock in the regulation of
      expression of genes required for ribulose-1,5-bisphosphate carboxylase/oxygenase
      (Rubisco) synthesis, assembly, and activation. Circadian oscillations in RCA (the
      gene encoding Rubisco activase) and RBCS (the gene encoding Rubisco small
      subunit) mRNA accumulation, with peak abundance occurring soon after dawn, occur
      in Arabidopsis thaliana grown in a light-dark (LD) photoperiod. These
      oscillations persist in plants that have been transferred from LD to either
      continuous darkness (DD) or continuous light (LL). In contrast, CPN60[alpha] (the
      gene encoding [alpha]-chaperonin) and CPN60[beta] (the gene encoding [beta]
      chaperonin) mRNA abundance oscillates in a diurnal, but not in a circadian,
      fashion. Although rapid damping of the circadian oscillation in RCA mRNA
      abundance is observed in Arabidopsis that have been grown in LD and then
      transferred to DD for 2 d, the circadian oscillations in RCA and RBCS mRNA
      abundance persist for at least five continuous cycles in LL, demonstrating the
      robustness of the circadian oscillator.

PMID- 12231962
TI  - Multiple Effects of Dithiothreitol on Nonphotochemical Fluorescence Quenching in
      Intact Chloroplasts (Influence on Violaxanthin De-epoxidase and Ascorbate
      Peroxidase Activity).
AB  - Reversible nonphotochemical fluorescence quenching depends on thylakoid lumen
      acidification and violaxanthin de-epoxidation and is correlated with
      photoprotection of photosynthesis. The O2-dependent electron flow in the coupled
      Mehler-ascorbate peroxidase reaction (MP-reaction) mediates the electron flow
      necessary for lumen acidification and violaxanthin de-epoxidation in isolated,
      intact chloroplasts. Inhibition of violaxanthin de-epoxidation by dithiothreitol
      (DTT) was correlated with suppression of fluorescence quenching. In addition, DTT
      was also found to suppress fluorescence quenching due to inhibition of ascorbate
      peroxidase activity, a main enzyme of the MP-reaction, even in the presence of
      zeaxanthin. In intact, non-CO2-fixing chloroplasts, violaxanthin and
      antheraxanthin de-epoxidation and the ascorbate peroxidase activity show
      different sensitivities to increasing DTT concentrations. Violaxanthin de
      epoxidase activity, measured as the sum of zeaxanthin and antheraxanthin formed,
      was inhibited with an inhibitor concentration for 50% inhibition (I50) of 0.35 mM
      DTT. In contrast, inhibition of the O2-dependent electron flow and corresponding
      lumen acidification occurred with higher I50 values of 2.5 and 3 mM DTT,
      respectively, and was attributed to inhibition of ascorbate peroxidase activity
      (I50 = 2 mM DTT). Accordingly, the DTT-induced inhibition of the nigericin
      sensitive nonphotochemical fluorescence quenching was correlated linearly with
      the decreasing concentrations of zeaxanthin and antheraxanthin and was almost
      unaffected by DTT inhibition of the MP-reaction and correlated [delta]pH. The
      nigericin-insensitive, photoinhibitory kind of nonphotochemical fluorescence
      quenching up to 1 mM was mainly correlated with inhibition of violaxanthin de
      epoxidation. At higher DTT concentrations, it was attributed to inhibition of
      both violaxanthin de-epoxidation and MP-reaction. The results show that DTT has
      multiple, but distinguishable, effects on nonphotochemical fluorescence quenching
      in isolated chloroplasts, necessitating careful interpretation.

PMID- 12231963
TI  - A Purified Zinc Protease of Pea Chloroplasts, EP1, Degrades the Large Subunit of
      Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase.
AB  - A previously reported endopeptidase (EP1) from pea chloroplasts was purified over
      11,000-fold using a four-step protocol involving ultrafiltration, sucrose
      gradient centrifugation, isoelectric focusing, and high performance liquid
      chromatography gel filtration. The enzyme was determined to be a metalloprotease
      requiring bound Zn2+ and added Mg2+ or Ca2+ for proper activity. Its localization
      in the stroma of pea chloroplasts was confirmed by demonstrating its
      insensitivity to thermolysin when the envelope was intact. A contaminating serine
      protease that attacks EP1 was found. The contaminating protease was inhibited by
      4-(2-aminoethyl)-benzenesulfonyl fluoride, but not by o-phenanthroline, whereas
      EP1 sensitivities were the reverse. EP1 is able to hydrolyze the large subunit of
      native ribulose-1,5-bisphosphate carboxylase/oxygenase under physiological
      conditions.

PMID- 12231964
TI  - Penetration by Artificial Electron Acceptors of the Plasma Membrane-Bound Redox
      System into Intact Zea mays L. Roots Investigated by Proton-Induced X-Ray
      Emission.
AB  - Proton-induced x-ray emission was used to investigate the penetration of
      compounds of the membrane-impermeant electron acceptors hexabromoiridate IV,
      hexachloroiridate IV, and hexacyanoferrate III into corn (Zea mays L.) roots.
      Maps of the heavy element distribution in cross-sections of fixed, epoxy-embedded
      roots showed for hexabromoiridate IV small amounts of Br in samples treated for
      24 h with concentrations normally used in physiological experiments (0.02 mM).
      After treatment with high concentrations (0.8 mM) of these complexes, Fe and Ir
      as well as Br were found in root cross-sections. In samples taken at a distance
      of 5 mm behind the root tip, we found an even distribution of Fe, Ir, and Br over
      the whole cross-section. In samples taken 15 mm behind the root tip, about 99% of
      both Br and Ir was confined to the rhizodermal cell layer. The distribution did
      not change with the complex used. These data are consistent with the view that
      apoplastic diffusion of the electron acceptors was blocked by the hypodermal
      Casparian band.

PMID- 12231965
TI  - Characterization of Expression of Drought- and Abscisic Acid-Regulated Tomato
      Genes in the Drought-Resistant Species Lycopersicon pennellii.
AB  - A number of genes are induced by drought stress, and some of these genes are
      regulated by the plant hormone abscisic acid (ABA). In tomato (Lycopersicon
      esculentum), four genes have been identified and isolated that require elevated
      levels of endogenous ABA for expression: le4, le16, le20, and le25. To gain a
      better understanding of the role of these genes during stress, their expression
      has been studied in the drought-resistant relative of tomato, Lycopersicon
      pennellii. It was determined that homologous genes to all four of the L.
      esculentum genes were present in the L. pennellii genome. Studies were undertaken
      to compare the expression characteristics of these genes in L. esculentum, L.
      pennellii, and their F1. Using two methods of water-deficit imposition, whole
      plants to which water was withheld and detached leaves that were wilted to 88% of
      their original fresh weight, it was demonstrated that transcripts of these genes
      accumulated in L. pennellii in response to water deficit. In general, the
      increase occurred after a longer period of water deficit in L. pennellii than in
      tomato. As in drought-sensitive species, ABA levels were elevated by drought
      stress in L. pennellii, although the levels were reduced compared with those in
      tomato. All four tomato genes were responsive to ABA in L. esculentum and the F1,
      but only three of the four genes (le16, le20, and le25) were induced in response
      to exogenous application of ABA in L. pennellii. The patterns of expression of
      these genes in L. pennellii are generally similar to that of L esculentum;
      therefore, it is suggested that these genes play a similar, yet undefined, role
      in both genotypes rather than being genes that are responsible for the greater
      drought resistance of L. pennellii.

PMID- 12231966
TI  - Relationship between Proline and Abscisic Acid in the Induction of Chilling
      Tolerance in Maize Suspension-Cultured Cells.
AB  - Both proline and abscisic acid (ABA) induce chilling tolerance in chilling
      sensitive plants. However, the relationship between proline and ABA in the
      induction of chilling tolerance is unclear. We compared the time course of the
      increase in chilling tolerance induced by proline and ABA, and the time course of
      the uptake of both into the cultured cells of maize (Zea mays L. cv Black Mexican
      Sweet) at 28[deg]C. The plateau of proline-induced chilling tolerance preceded by
      12 h the plateau of ABA-induced chilling tolerance. The uptake of exogenous ABA
      into the cells reached a plateau in 1 h, whereas the uptake of exogenous proline
      gradually increased throughout the 24-h culture period. Although the proline
      content in ABA-treated cells was 2-fold higher than in untreated cells at the end
      of the 24-h ABA treatment at 28[deg]C, the correlation between the endogenous
      free proline content and the chilling tolerance in the ABA-treated cells was
      insignificant. Isobutyric acid treatment, which resulted in a larger accumulation
      of proline in the cells than ABA treatment, did not increase chilling tolerance.
      The induction of chilling tolerance by proline and ABA appeared to be additive.
      Cycloheximide inhibited ABA-induced chilling tolerance, but it did not inhibit
      proline-induced chilling tolerance. Newly synthesized proteins accumulate in ABA
      treated cells at 28[deg]C while the chilling tolerance is developing (Z. Xin and
      P.H. Li [1993] Plant Physiol 101: 277-284), but none of these proteins were
      observed in the proline-treated cells. Results suggest that proline and ABA
      induce chilling tolerance in maize cultured cells by different mechanisms.

PMID- 12231967
TI  - The Cytochrome c Reductase Integrated Processing Peptidase from Potato
      Mitochondria Belongs to a New Class of Metalloendoproteases.
AB  - The general mitochondrial processing peptidase that removes the N-terminal
      targeting signals from proteins imported into mitochondria forms part of a
      respiratory protein complex in potato (Solanum tuberosum L.). We have termed this
      complex the "cytochrome c reductase/processing peptidase complex" and show that
      it acts on a variety of precursor proteins from different intramitochondrial
      locations. In potato, biochemical methods fail to separate the ubiquinol
      cytochrome c oxidoreductase function from the function of the processing
      protease. On the other hand, inhibition of electron flow with antimycin A or
      myxothiazol does not affect processing activity. The integration into an
      oligomeric protein complex causes the unique properties of the processing enzyme.
      It is fully active at high pH and in the presence of high salt. It does not need
      externally added metal ions, but it is inhibited by EDTA and 1,10-phenanthroline.
      Other protease inhibitors have no effect on the processing activity. Taken
      together, the molecular genetic and physiological results indicate that the
      mitochondrial processing protease does not belong to the thermolysin superfamily
      of metalloproteinases but may be a member of a new class of metalloendoproteases.

PMID- 12231968
TI  - Oxidative Stimulation of Glutathione Synthesis in Arabidopsis thaliana Suspension
      Cultures.
AB  - A system based on Arabidopsis thaliana suspension cultures was established for
      the analysis of glutathione (GSH) synthesis in the presence of hydrogen peroxide.
      Mild oxidative stress was induced by use of the catalase inhibitor,
      aminotriazole, and its development was monitored by measurement of the oxidative
      inactivation of aconitase. Addition of 2 mM aminotriazole resulted in a 25%
      decrease in activity of aconitase over 4 h. During the subsequent 10 h, no
      further decrease in aconitase activity was measured despite a sustained
      inhibition of catalase. In combination with our failure to detect significant
      increases in the level of lipid peroxidation, another marker indicative of
      oxidative injury, these data suggest that although hydrogen peroxide initially
      leaked into the cytosol, its accumulation was limited by a cytosolic catalase
      independent mechanism. A 4-fold increase in the level of GSH, which was almost
      exclusively in the reduced form, was observed under the same treatment. To
      determine to what extent this increase in reduced GSH played a role in limiting
      the accumulation of hydrogen peroxide in the cytosol, we inhibited GSH synthesis
      with buthionine sulfoximine (BSO), a specific inhibitor of [gamma]
      glutamylcysteine synthetase. No significant oxidative injury was detected as a
      result of treatment with 50 [mu]M BSO alone, and furthermore, this treatment had
      no effect on cell viability, However, addition of 2 mM aminotriazole to cells
      preincubated with 50 [mu]M BSO for 15 h led to a rapid loss of aconitase activity
      (75% in 4 h), and significant accumulation of products of lipid peroxidation.
      Within 72 h, cell viability was lost completely. After removal of BSO from the
      growth medium, GSH levels recovered to normal over a period of 20 h. Addition of
      2 mM aminotriazole to cells at different time points during this recovery period
      demonstrated a strong correlation between the level of reduced GSH and the degree
      of protection against oxidative injury. These data strongly suggest that the
      induction of GSH synthesis by an oxidative stimulus plays a crucial role in
      determining the susceptibility of cells to oxidative stress.

PMID- 12231969
TI  - Use of Transgenic Plants with Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase
      Antisense DNA to Evaluate the Rate Limitation of Photosynthesis under Water
      Stress.
AB  - The biochemical lesion that causes impaired chloroplast metabolism (and, hence,
      photosynthetic capacity) in plants exposed to water deficits is still a subject
      of controversy. In this study we used tobacco (Nicotiana tabacum L.) transformed
      with "antisense" ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) DNA
      sequences to evaluate whether Rubisco or some other enzymic step in the
      photosynthetic carbon reduction cycle pathway rate limits photosynthesis at low
      leaf water potential ([psi]w). These transformants, along with the wild-type
      material, provided a novel model system allowing for an evaluation of
      photosynthetic response to water stress in near-isogenic plants with widely
      varying levels of functional Rubisco. It was determined that impaired chloroplast
      metabolism (rather than decreased leaf conductance to CO2) was the major cause of
      photosynthetic inhibition as leaf [psi]w declined. Significantly, the extent of
      photosynthetic inhibition at low [psi]w was identical in wild-type and
      transformed plants. Decreasing Rubisco activity by 68% did not sensitize
      photosynthetic capacity to water stress. It was hypothesized that, if water
      stress effects on Rubisco caused photosynthetic inhibition under stress, an
      increase in the steady-state level of the substrate for this enzyme, ribulose 1,5
      bisphosphate (RuBP), would be associated with stress-induced photosynthetic
      inhibition. Steady-state levels of RuBP were reduced as leaf [psi]w declined,
      even in transformed plants with low levels of Rubisco. Based on the similarity in
      photosynthetic response to water stress in wild-type and transformed plants, the
      reduction in RuBP as stress developed, and studies that demonstrated that ATP
      supply did not rate limit photosynthesis under stress, we concluded that stress
      effects on an enzymic step involved in RuBP regeneration caused impaired
      chloroplast metabolism and photosynthetic inhibition in plants exposed to water
      deficits.

PMID- 12231970
TI  - Changes in P-700 Oxidation during the Early Stages of the Induction of
      Photosynthesis.
AB  - Following dark adaptation, the response to irradiance of chlorophyll (Chl)
      fluorescence, the light-induced absorbance change around 820 nm (to measure
      reaction center Chl of photosystem I [PSI] P-700 oxidation), and CO2 fixation
      were examined in pea (Pisum sativum L.) leaves under a range of conditions.
      Initially, P-700 oxidation is restricted by a lack of regeneration of PSI
      electron acceptors, and the increase of oxidized P-700 (P-700+) that occurs
      during approximately the first 60 s of irradiation is largely independent of the
      resistance to electron flow between the two photosystems. Under these conditions,
      the quantum efficiency for linear electron flow is directly positively related to
      P-700+ accumulation, which is in contrast to the direct negative correlation that
      is the most frequently reported relationship between P-700+ accumulation and the
      quantum efficiency for linear electron flow.

PMID- 12231971
TI  - Illuminating Phytochrome Functions (There Is Light at the End of the Tunnel).

PMID- 12231972
TI  - Aluminum Tolerance in Wheat (Triticum aestivum L.) (I. Uptake and Distribution of
      Aluminum in Root Apices).
AB  - We investigated the uptake and distribution of Al in root apices of near-isogenic
      wheat (Triticum aestivum L.) lines differing in Al tolerance at a single locus
      (Alt1: aluminum tolerance). Seedlings were grown in nutrient solution that
      contained 100 [mu]M Al, and the roots were subsequently stained with hematoxylin,
      a compound that binds Al in vitro to form a colored complex. Root apices of Al
      sensitive genotypes stained after short exposures to Al (10 min and 1 h), whereas
      apices of Al-tolerant seedlings showed less intense staining after equivalent
      exposures. Differential staining preceded differences observed in either root
      elongation or total Al concentrations of root apices (terminal 2-3 mm of root).
      After 4 h of exposure to 100 [mu]M Al in nutrient solution, Al-sensitive
      genotypes accumulated more total Al in root apices than Al-tolerant genotypes,
      and the differences became more marked with time. Analysis of freeze-dried root
      apices by x-ray microanalysis showed that Al entered root apices of Al-sensitive
      plants and accumulated in the epidermal layer and in the cortical layer
      immediately below the epidermis. Long-term exposure of sensitive apices to Al (24
      h) resulted in a distribution of Al coinciding with the absence of K.
      Quantitation of Al in the cortical layer showed that sensitive apices accumulated
      5- to 10-fold more Al than tolerant apices exposed to Al solutions for equivalent
      times. These data are consistent with the hypothesis that Alt1 encodes a
      mechanism that excludes Al from root apices.

PMID- 12231973
TI  - Aluminum Tolerance in Wheat (Triticum aestivum L.) (II. Aluminum-Stimulated
      Excretion of Malic Acid from Root Apices).
AB  - We investigated the role of organic acids in conferring Al tolerance in near
      isogenic wheat (Triticum aestivum L.) lines differing in Al tolerance at the Al
      tolerance locus (Alt1). Addition of Al to nutrient solutions stimulated excretion
      of malic and succinic acids from roots of wheat seedlings, and Al-tolerant
      genotypes excreted 5- to 10-fold more malic acid than Al-sensitive genotypes.
      Malic acid excretion was detectable after 15 min of exposure to 200 [mu]M Al, and
      the amount excreted increased linearly over 24 h. The amount of malic acid
      excreted was dependent on the external Al concentration, and excretion was
      stimulated by as little as 10 [mu]M Al. Malic acid added to nutrient solutions
      was able to protect Al-sensitive seedlings from normally phytotoxic Al
      concentrations. Root apices (terminal 3-5 mm of root) were the primary source of
      the malic acid excreted. Root apices of Al-tolerant and Al-sensitive seedlings
      contained similar amounts of malic acid before and after a 2-h exposure to 200
      [mu]M Al. During this treatment, Al-tolerant seedlings excreted about four times
      the total amount of malic acid initially present within root apices, indicating
      that continual synthesis of malic acid was occurring. Malic acid excretion was
      specifically stimulated by Al, and neither La, Fe, nor the absence of Pi was able
      to elicit this response. There was a consistent correlation of Al tolerance with
      high rates of malic acid excretion stimulated by Al in a population of seedlings
      segregating for Al tolerance. These data are consistent with the hypothesis that
      the Alt1 locus in wheat encodes an Al tolerance mechanism based on Al-stimulated
      excretion of malic acid.

PMID- 12231974
TI  - Expression and Localization of Plant Protein Disulfide Isomerase.
AB  - A cDNA clone encoding a putative protein disulfide isomerase (PDI, EC 5.3.4.1)
      from alfalfa (Medicago sativa L.) was expressed in Escherichia coli cells, and an
      antiserum was raised against the expressed PDI-active protein. The antiserum
      recognized a protein of approximately 60 kD in extracts from alfalfa, soybean,
      and tobacco roots and stems. Levels of this protein remained relatively constant
      on exposure of alfalfa cell suspension cultures to the protein glycosylation
      inhibitor tunicamycin, whereas a slightly lower molecular mass form, also
      detected by the antiserum, was induced by this treatment. A lower molecular mass
      form of PDI was also observed in roots of alfalfa seedlings during the first 5
      weeks after germination. PDI levels increased in developing soybean seeds up to
      17 d after fertilization and then declined. Tissue print immunoblots revealed
      highest levels of PDI protein in the cambial tissues of soybean stems and
      petioles and in epidermal, subepidermal, cortical, and pith tissues of stems of
      alfalfa and tobacco. Immunogold electron microscopy confirmed the localization of
      PDI to the endoplasmic reticulum in soybean root nodules.

PMID- 12231975
TI  - Purification and Properties of a Monofunctional Imidazoleglycerol-Phosphate
      Dehydratase from Wheat.
AB  - Imidazoleglycerol-phosphate dehydratase (EC 4.2.1.19) activity was detected in
      extracts of several monocotyledonous and dicotyledonous plants using a newly
      developed assay method. The enzyme was purified 114,000-fold (to apparent
      homogeneity) from wheat germ by five chromatographic steps. Its native relative
      molecular weight (Mr) was determined to be 600,000 to 670,000, and it consists of
      identical subunits of Mr 25,500. In wheat germ, the dehydratase, unlike those of
      prokaryotic origin, is not associated with histidinol phosphatase activity. The
      reaction product was identified as imidazoleacetol phosphate (IAP) by comparing
      it with synthetic IAP as an authentic reference. The Km value for
      imidazoleglycerol phosphate was 0.36 mM at the optimal pH of 6.6. The enzyme
      required a reducing agent, such as 2-mercaptoethanol or dithiothreitol, and Mn2+
      for maximal activity. 3-Amino-1,2,4-triazole competitively inhibited the activity
      with a Ki value of 46 [mu]M. The purification of imidazoleglycerol-phosphate
      dehydratase from wheat germ and histidinol dehydrogenase from cabbage (A. Nagai,
      A. Scheidegger [1991] Arch Biochem Biophys 284: 127-132) suggests that at least
      the second half of the histidine biosynthesis in plants is identical to that in
      microorganisms.

PMID- 12231976
TI  - The Role of Flavonol Glycosides and Carotenoids in Protecting Soybean from
      Ultraviolet-B Damage.
AB  - The increase in ultraviolet-B (UV-B; 0.290-0.320 [mu]m) radiation received by
      plants due to stratospheric ozone depletion heightens the importance of
      understanding UV-B tolerance. Photosynthetic tissue is believed to be protected
      from UV-B radiation by UV-B-absorbing compounds (e.g. flavonoids). Although
      synthesis of flavonoids is induced by UV-B radiation, its protective role on
      photosynthetic pigments has not been clearly demonstrated. This results in part
      from the design of UV-B experiments in which experimental UV-A irradiance has not
      been carefully controlled, since blue/UV-A radiation is involved in the
      biosynthesis of the photosynthetic pigments. The relationship of flavonoids to
      photosynthetic performance, photosynthetic pigments, and growth measures was
      examined in an experiment where UV-A control groups were included at two
      biologically effective daily UV-B irradiances, 14.1 and 10.7 kJ m-2. Normal,
      chlorophyll-deficient, and flavonoid-deficient pigment isolines of two soybean
      (Glycine max) cultivars that produced different flavonol glycosides (Harosoy
      produced kaempferol, Clark produced quercetin and kaempferol) were examined.
      Plants with higher levels of total flavonoids, not specific flavonol glycosides,
      were more UV-B tolerant as determined by growth, pigment, and gas-exchange
      variables. Regression analyses indicated no direct relationship between
      photosynthesis and leaf levels of UV-B-absorbing compounds. UV-B radiation
      increased photosynthetic pigment content, along with UV-B-absorbing compounds,
      but only the former (especially carotenoids) was related to total biomass (r2 =
      0.61, linear) and to photosynthetic efficiency (negative, exponential
      relationship, r2 = 0.82). A reduction in photosynthesis was associated primarily
      with a stomatal limitation rather than photosystem II damage. This study suggests
      that both carotenoids and flavonoids may be involved in plant UV-B
      photoprotection, but only carotenoids are directly linked to photoprotection of
      photosynthetic function. These results additionally show the importance of UV-A
      control in UV-B experiments conducted using artificial lamps and filters.

PMID- 12231977
TI  - Ultrastructural Evidence That Intracellular Ice Formation and Possibly Cavitation
      Are the Sources of Freezing Injury in Supercooling Wood Tissue of Cornus florida
      L.
AB  - Although cellular injury in some woody plants has been correlated with freezing
      of supercooled water, there is no direct evidence that intracellular ice
      formation is responsible for the injury. In this study we tested the hypothesis
      that injury to xylem ray parenchyma cells in supercooling tissues is caused by
      intracellular ice formation. The ultrastructure of freezing-stress response in
      xylem ray parenchyma cells of flowering dogwood (Cornus florida L.) was
      determined in tissue prepared by freeze substitution. Wood tissue was collected
      in the winter, spring, and summer of 1992. Specimens were cooled from 0 to 
      60[deg]C at a rate of 5[deg]C h-1. Freezing stress did not affect the structural
      organization of wood tissue, but xylem ray parenchyma cells suffered severe
      injury in the form of intracellular ice crystals. The temperatures at which the
      ice crystals were first observed depended on the season in which the tissue was
      collected. Intracellular ice formation was observed at -20, -10, and -5[deg]C in
      winter, spring, and summer, respectively. Another type of freezing injury was
      manifested by fragmented protoplasm with indistinguishable plasma membranes and
      damaged cell ultrastructure but no evidence of intracellular ice. Intracellular
      cavitation may be a source of freezing injury in xylem ray parenchyma cells of
      flowering dogwood.

PMID- 12231978
TI  - Effects of Boron on Proton Transport and Membrane Properties of Sunflower
      (Helianthus annuus L.) Cell Microsomes.
AB  - Boron deficiency and toxicity inhibit ATP-dependent H+ pumping and vanadate
      sensitive ATPase activity in sunflower roots and cell suspensions. The effects of
      boron on H+ pumping and on passive H+ conductance, as well as on fluorescence
      anisotropy in KI-washed microsomes isolated from sunflower (Helianthus annuus L.
      cv Enano) cell suspensions, have been investigated. Boron deficiency reduced the
      total and vanadate-sensitive ATPase activities as well as the vanadate-sensitive
      ATP-dependent H+ pumping without affecting the amount of antigenic ATPase protein
      as measured by immunoblotting with an Arabidopsis thaliana plasma membrane anti
      H+-ATPase polyclonal antibody. Kinetic studies revealed that boron deficiency
      reduced Vmax of vanadate-sensitive ATPase activity with little change in the
      apparent Km for Mg2+-ATP. Proton leakage was greater in microsomal vesicles
      isolated from cells grown without boron and incubated in reaction medium without
      added boron, and this effect was reversed by addition of boron to the reaction
      medium. Fluorescence anisotropy indicated that diphenyl hexatriene and 1-(4
      trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene probes were immobilized to a
      greater extent in microsomes from cells grown without boron than in those from
      cells grown with 100 [mu]M H3BO3. The apparent decrease of membrane fluidity in
      microsomes from cells grown without boron was reversed by the addition of boron
      to the reaction medium. Taken together these data suggest that inhibition of H+
      gradient formation in microsomes from sunflower cells grown in the absence of
      boron could be due to the combined effects of reduced H+-ATPase activity and
      increased passive conductance across the membrane, possibly resulting from
      increased membrane rigidity.

PMID- 12231979
TI  - Submergence-Induced Ethylene Synthesis, Entrapment, and Growth in Two Plant
      Species with Contrasting Flooding Resistances.
AB  - Submergence-induced ethylene synthesis and entrapment were studied in two
      contrasting Rumex species, one flood-resistant (Rumex palustris) and the other
      flood-sensitive (Rumex acetosa). The application of a photoacoustic method to
      determine internal ethylene concentrations in submerged plants is discussed. A
      comparison with an older technique (vacuum extraction) is described. For the
      first time ethylene production before, during, and after submergence and the
      endogenous concentration during submergence were continuously measured on a
      single intact plant without physical perturbation. Both Rumex species were
      characterized by enhanced ethylene concentrations in the shoot after 24 h of
      submergence. This was not related to enhanced synthesis but to continued
      production and physical entrapment. In R. palustris, high endogenous ethylene
      levels correlated with enhanced petiole and lamina elongation. No dramatic change
      in leaf growth rate was observed in submerged R. acetosa shoots. After
      desubmergence both species showed an increase in ethylene production, the
      response being more pronounced in R. palustris. This increase was linked to the
      enhanced postsubmergence growth rate of leaves of R. palustris. Due to the very
      rapid escape of ethylene out of desubmerged plants to the atmosphere (90%
      disappeared within 1 min), substantial underestimation of internal ethylene
      concentrations can be expected using more conventional vacuum extraction
      techniques.

PMID- 12231980
TI  - Plasma Membrane Lipids Associated with Genetic Variability in Freezing Tolerance
      and Cold Acclimation of Solanum Species.
AB  - Simultaneous comparisons were made between a freezing-tolerant, cold-acclimating
      (CA) wild potato species (Solanum commersonii) and a freezing-sensitive,
      nonacclimating (NA) cultivated species (Solanum tuberosum). Comparative studies
      allowed differentiation of plasma membrane lipid changes associated with
      increased freezing tolerance following CA from lipid changes that can result from
      metabolic adjustment to reduced temperature during CA. Following CA treatment
      lipid changes found in both the NA and CA species included a decrease in palmitic
      acid, an increase in unsaturated to saturated fatty acid ratio, an increase in
      free sterols, an increase in sitosterol, and a slight decrease in cerebrosides.
      Lipid changes detected only in the acclimating species included an increase in
      phosphatidylethanolamine, a decrease in sterol to phospholipid ratio, an increase
      in linoleic acid, a decrease in linolenic acid, and an increase in acylated
      steryl glycoside to steryl glycoside ratio. These changes were either absent or
      opposite in the NA species, suggesting an association of these lipid changes with
      CA. Furthermore, the lipid changes associated with increased freezing tolerance
      during CA were distinct from lipid differences between the two species in the NA
      state.

PMID- 12231981
TI  - Concurrent Measurements of Oxygen and Carbon Dioxide Exchange during Lightflecks
      in Maize (Zea mays L.).
AB  - Leaves of maize (Zea mays L.) were enclosed in a temperature-controlled cuvette
      under 35 Pa (350 [mu]bars) CO2 and 0.2 kPa (0.2%)O2 and exposed to short periods
      (1-30 s) of illumination (light-flecks). The rate and total amount of CO2
      assimilated and O2 evolved were measured. The O2 evolution rate was taken as an
      indicator of the rate of photosynthetic noncyclic electron transport (NCET). In
      this C4 species, the response of electron transport during the lightflecks
      qualitatively mimicked that of C3 species previously tested, whereas the response
      of CO2 assimilation differed. Under short-duration lightflecks at high photon
      flux density (PFD), the mean rate of O2 evolution was greater than the steady
      state rate of O2 evolution under the same PFD due to a burst of O2 evolution at
      the beginning of the lightfleck. This O2 burst was taken as indicating a high
      level of NCET involved in the buildup of assimilatory charge via ATP, NADPH, and
      reduced or phosphorylated metabolites. However, as lightfleck duration decreased,
      the amount of CO2 assimilated per unit time of the lightfleck (the mean rate of
      CO2 assimilation) decreased. There was also a burst of CO2 from the leaf at the
      beginning of low-PFD lightflecks that further reduced the assimilation during
      these lightflecks. The results are discussed in terms of the buildup of
      assimilatory charge through the synthesis of high-energy metabolites specific to
      C4 metabolism. It is speculated that the inefficiency of carbon uptake during
      brief light transients in the C4 species, relative to C3 species, is due to the
      futile synthesis of C4 cycle intermediates.

PMID- 12231982
TI  - Photoinhibition and D1 Protein Degradation in Peas Acclimated to Different Growth
      Irradiances.
AB  - The relationship between the susceptibility of photosystem II (PSII) to
      photoinhibition in vivo and the rate of degradation of the D1 protein of the PSII
      reaction center heterodimer was investigated in leaves from pea plants (Pisum
      sativum L. cv Greenfeast) grown under widely contrasting irradiances. There was
      an inverse linear relationship between the extent of photoinhibition and
      chlorophyll (Chl) a/b ratios, with low-light leaves being more susceptible to
      high light. In the presence of the chloroplast-encoded protein synthesis
      inhibitor lincomycin, the differential sensitivity of the various light
      acclimated pea leaves to photoinhibition was largely removed, demonstrating the
      importance of D1 protein turnover as the most crucial mechanism to protect
      against photoinhibition. In the differently light-acclimated pea leaves, the rate
      of D1 protein degradation (measured from [35S]methionine pulse-chase experiments)
      increased with increasing incident light intensities only if the light was not
      high enough to cause photoinhibition in vivo. Under moderate illumination, the
      rate constant for D1 protein degradation corresponded to the rate constant for
      photoinhibition in the presence of lincomycin, demonstrating a balance between
      photodamage to D1 protein and subsequent recovery, via D1 protein degradation, de
      novo synthesis of precursor D1 protein, and reassembly of functional PSII. In
      marked contrast, in light sufficiently high to cause photoinhibition in vivo, the
      rate of D1 protein degradation no longer increased concomitantly with increasing
      photoinhibition, suggesting that the rate of D1 protein degradation is playing a
      regulatory role. The extent of thylakoid stacking, indicated by the Chl a/b
      ratios of the differently light-acclimated pea leaves, was linearly related to
      the half-life of the D1 protein in strong light. We conclude that photoinhibition
      in vivo occurs under conditions in which the rate of D1 protein degradation can
      no longer be enhanced to rapidly remove irreversibly damaged D1 protein. We
      suggest that low-light pea leaves, with more stacked membranes and less stroma
      exposed thylakoids, are more susceptible to photoinhibition in vivo mainly due to
      their slower rate of D1 protein degradation under sustained high light and their
      slower repair cycle of the photodamaged PSII centers.

PMID- 12231983
TI  - Covalent and Noncovalent Dimers of the Cyanide-Resistant Alternative Oxidase
      Protein in Higher Plant Mitochondria and Their Relationship to Enzyme Activity.
AB  - Evidence for a mixed population of covalently and noncovalently associated dimers
      of the cyanide-resistant alternative oxidase protein in plant mitochondria is
      presented. High molecular mass (oxidized) species of the alternative oxidase
      protein, having masses predicted for homodimers, appeared on immunoblots when the
      sulfhydryl reductant, dithiothreitol (DTT), was omitted from sodium dodecyl
      sulfate-polyacrylamide gel sample buffer. These oxidized species were observed in
      mitochondria from soybean (Glycine max [L.] Merr. cv Ransom), Sauromatum guttatum
      Schott, and mung bean (Vigna radiata [L.] R. Wilcz). Reduced species of the
      alternative oxidase were also present in the same mitochondrial samples. The
      reduced and oxidized species in isolated soybean cotyledon mitochondria could be
      interconverted by incubation with the sulfhydryl reagents DTT and azodicarboxylic
      acid bis(dimethylamide) (diamide). Treatment with chemical cross-linkers resulted
      in cross-linking of the reduced species, indicating a noncovalent dimeric
      association among the reduced alternative oxidase molecules. Alternative pathway
      activity of soybean mitochondria increased following reduction of the alternative
      oxidase protein with DTT and decreased following oxidation with diamide,
      indicating that electron flow through the alternative pathway is sensitive to the
      sulfhydryl/disulfide redox poise. In mitochondria from S. guttatum floral
      appendix tissue, the proportion of the reduced species increased as development
      progressed through thermogenesis.

PMID- 12231984
TI  - Expression of Acid Invertase Gene Controls Sugar Composition in Tomato
      (Lycopersicon) Fruit.
AB  - A wild tomato species, Lycopersicon chmielewskii, accumulates high levels of
      soluble sugar in mature fruit and, unlike the domesticated tomato species,
      Lycopersicon esculentum, accumulates sucrose rather than glucose and fructose.
      Genetic and biochemical analyses of progeny resulting from a cross of L.
      chmielewskii with L. esculentum have previously indicated that the trait of
      sucrose accumulation is controlled by a single recessive gene and is associated
      with low levels of acid invertase protein in the developing fruit. Analysis of
      progeny from the BC2F3 generation from the L. esculentum x L. chmielewskii cross
      revealed that sucrose-accumulating fruit accumulate sugar in two phases
      corresponding to fruit expansion and fruit maturation and that the majority of
      the sucrose was stored in the latter phase after the fruit had reached maximum
      size. The only significant enzymic difference between the sucrose-accumulating
      and hexose-accumulating fruit was the lack of acid invertase activity in sucrose
      accumulating fruit. Sucrose phosphate synthase activity did not increase in the
      sucrose-accumulating fruit during late development when the rate of sucrose
      accumulation increased. The lack of acid invertase activity in sucrose
      accumulating fruit was correlated with inheritance of the L. chmielewskii acid
      invertase gene and the absence of acid invertase mRNA in developing fruit. This
      suggests that the L.chmielewskii invertase gene is transcriptionally silent in
      fruit and that this is the basis for sucrose accumulation in progeny derived from
      the interspecific cross of L. esculentum and L. chmielewskii.

PMID- 12231985
TI  - Exogenous Abscisic Acid Mimics Cold Acclimation for Cacti Differing in Freezing
      Tolerance.
AB  - The responses to low temperature were determined for two species of cacti
      sensitive to freezing, Ferocactus viridescens and Opuntia ficus-indica, and a
      cold hardy species, Opuntia fragilis. Fourteen days after shifting the plants
      from day/night air temperatures of 30/20[deg]C to 10/0[deg]C, the chlorenchyma
      water content decreased only for O. fragilis. This temperature shift caused the
      freezing tolerance (measured by vital stain uptake) of chlorenchyma cells to be
      enhanced only by about 2.0[deg]C for F. viridescens and O. ficus-indica but by
      14.6[deg]C for O. fragilis. Also, maintenance of high water content by injection
      of water into plants at 10/0[deg]C reversed the acclimation. The endogenous
      abscisic acid (ABA) concentration was below 0.4 pmol g-1 fresh weight at
      30/20[deg]C, but after 14 d at 10/0[deg]C it increased to 84 pmol g-1 fresh
      weight for O. ficus-indica and to 49 pmol g-1 fresh weight for O. fragilis. Four
      days after plants were sprayed with 7.5 x 10-5 M ABA at 30/20[deg]C, freezing
      tolerance was enhanced by 0.5[deg]C for F. viridescens, 4.1[deg]C for O. ficus
      indica, and 23.4[deg]C for O. fragilis. Moreover, the time course for the change
      in freezing tolerance over 14 d was similar for plants shifted to low
      temperatures as for plants treated with exogenous ABA at moderate temperatures.
      Decreases in plant water content and increases in ABA concentration may be
      important for low-temperature acclimation by cacti, especially O. fragilis, which
      is widely distributed in Canada and the United States.

PMID- 12231986
TI  - Cytochrome and Alternative Pathway Respiration in Tobacco (Effects of Salicylic
      Acid).
AB  - In suspension cultures of NT1 tobacco (Nicotiana tabacum L. cv Bright Yellow)
      cells the cytochrome pathway capacity increased between d 3 and d 4 following
      subculturing and reached the highest level observed on d 7. The capacity
      decreased significantly by d 10 and was at the same level on d 14. Both
      alternative pathway capacity and the amount of the 35-kD alternative oxidase
      protein increased significantly between d 5 and d 6, reached the highest point
      observed on d 7, remained constant until d 10, and decreased by d 14. The highest
      capacities of the alternative and cytochrome pathways and the highest amount of
      the 35-kD protein were attained on the day that cell cultures reached a
      stationary phase of growth. Addition of salicylic acid to cell cultures on d 4
      caused a significant increase in alternative pathway capacity and a dramatic
      accumulation of the 35-kD protein by 12 h. The alternative pathway capacity and
      the protein level reached the highest level observed by 16 h after salicylic acid
      addition, and the cytochrome pathway capacity was at about the same level at each
      time point. The accumulation of the 35-kD alternative oxidase protein was
      significantly decreased by addition of actinomycin D 1 h before salicylic acid
      and was blocked by addition of cycloheximide. These results indicate that de novo
      transcription and translation were necessary for salicylic acid to cause the
      maximum accumulation of the 35-kD protein.

PMID- 12231987
TI  - Investigation of the Apparent Induction of Nitrate Uptake in Barley (Hordeum
      vulgare L.) Using NO3--Selective Microelectrodes (Modulation of Coarse Regulation
      of NO3- Uptake by Exogenous Application of Downstream Metabolites in the NO3-
      Assimilatory Pathway).
AB  - The influence of a 12-h pretreatment with either NO3-, NH4+, glutamine, or
      glutamate (300 [mu]M) on the apparent induction of NO3- uptake was investigated.
      Net fluxes of NO3- into roots of intact, 7-d-old barley (Hordeum vulgare L. cv
      Prato) seedlings in solution culture were estimated from ion activity gradients
      measured with NO3--selective microelectrodes in the unstirred layer of solution
      immediately external to the root surface. Control plants, pretreated with
      nitrogen-free nutrient solution, exhibited a sigmoidal increase in net NO3-
      uptake, reaching a maximum rate between 8 and 9 h after first exposure to NO3-.
      Plants pretreated with NH4+ or Glu exhibited a delay of several hours in the
      initiation of the induction process after they had been exposed to NO3-. In Gln
      pretreated plants, however, responses ranged from no delay of the induction
      process to delays comparable to those observed following NH4+ or Glu
      pretreatments. Only treatment with NO3-resulted in the induction of NO3- uptake,
      whereas pretreatments with NH4+, Gln, or Glu tended to delay induction of NO3-
      uptake upon subsequent exposure to NO3-.

PMID- 12231988
TI  - Ketol-Acid Reductoisomerase from Barley (Hordeum vulgare) (Purification,
      Properties, and Specific Inhibition).
AB  - Ketol-acid reductoisomerase (KARI, EC 1.1.1.86) was purified to homogeneity from
      etiolated barley shoots (Hordeum vulgare) using anion exchange, Red-Sepharose,
      hydrophobic interaction, and chromatofocusing steps. Purification yielded 0.25 to
      0.27 mg of pure KARI per 100 g fresh weight of starting material. The specific
      activity of the purified enzyme was 6 [mu]mol of NADPH oxidized min-1 mg-1 with
      acetohydroxybutyrate as substrate. The native enzyme had an apparent molecular
      weight of 115,000 as estimated by gel filtration and appeared to be a homodimer
      with a subunit molecular weight of 59,000, as determined by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. The Km values of the purified KARI
      for acetolactate, acetohydroxybutyrate, and NADPH (determined with
      acetohydroxybutyrate) were 11, 38, and 4.3 [mu]M, respectively. The Vmax obtained
      with acetohydroxybutyrate was 1.8 [mu]mol min-1 mg-1; the corresponding value for
      acetolactate was 0.16 [mu]mol min-1 mg-1. The enzyme showed optimum activity at
      pH 7.5. When either acetolactate or acetohydroxybutyrate was used as substrate,
      the experimental herbicidal compound 2-dimethyl-phosphinoyl-2-hydroxyacetic acid
      inhibited the purified KARI in a time-dependent and reversible manner. The
      initial inhibition was strictly competitive. The inhibition constant values were
      0.46 (using acetolactate as substrate) and 0.19 [mu]M (acetohydroxybutyrate),
      respectively.

PMID- 12231989
TI  - Effects of Acetyl-Coenzyme A Carboxylase Inhibitors on Root Cell Transmembrane
      Electric Potentials in Graminicide-Tolerant and -Susceptible Corn (Zea mays L.).
AB  - Herbicidal activity of aryloxyphenoxypropionate and cyclohexanedione herbicides
      (graminicides) has been proposed to involve two mechanisms: inhibition of acetyl
      coenzyme A carboxylase (ACCase) and depolarization of cell membrane potential. We
      examined the effect of aryloxyphenoxypropionates (diclofop and haloxyfop) and
      cyclohexanediones (sethoxydim and clethodim) on root cortical cell membrane
      potential of graminicide-susceptible and -tolerant corn (Zea mays L.) lines. The
      graminicide-tolerant corn line contained a herbicide-insensitive form of ACCase.
      The effect of the herbicides on membrane potential was similar in both corn
      lines. At a concentration of 50 [mu]M, the cyclohexanediones had little or no
      effect on the membrane potential of root cells. At pH 6, 50 [mu]M diclofop, but
      not haloxyfop, depolarized membrane potential, whereas both herbicides (50 [mu]M)
      dramatically depolarized membrane potential at pH 5. Repolarization of membrane
      potential after removal of haloxyfop and diclofop from the treatment solution was
      incomplete at pH 5. However, at pH 6 nearly complete repolarization of membrane
      potential occurred after removal of diclofop. In graminicide-susceptible corn,
      root growth was significantly inhibited by a 24-h exposure to 1 [mu]M haloxyfop
      or sethoxydim, but cell membrane potential was unaffected. In gramincide-tolerant
      corn, sethoxydim treatment (1 [mu]M, 48 h) had no effect on root growth, whereas
      haloxyfop (1 [mu]M, 48 h) inhibited root growth by 78%. However, membrane
      potential was the same in roots treated with 1 [mu]M haloxyfop or sethoxydim. The
      results of this study indicate that graminicide tolerance in the corn line used
      in this investigation is not related to an altered response at the cell membrane
      level as has been demonstrated with other resistant species.

PMID- 12231990
TI  - Five Nodulation Mutants of White Sweetclover (Melilotus alba Desr.) Exhibit
      Distinct Phenotypes Blocked at Root Hair Curling, Infection Thread Development,
      and Nodule Organogenesis.
AB  - In an effort to obtain a developmental sequence of mutations in the Rhizobium
      legume interaction within a single legume species, we have characterized the
      early events of nodule development in 10 nodulation mutants of sweetclover,
      Melilotus alba Desr. cv U389, representing five genetic loci. Both seed and root
      exudates from all of the sweetclover mutants induced expression of the nod genes
      of Rhizobium meliloti. Mutants in three loci were blocked in the early stages of
      root hair curling. Of these, a mutant in the sym-3 locus exhibited root hair
      deformations in response to inoculation with R. meliloti but produced no nodules
      or emerging nodule primordia, suggesting a blockage in the signal transduction
      events leading to nodule organogenesis. In contrast, mutants in both the sym-1
      and sym-5 loci formed ineffective nodules in response to inoculation but differed
      slightly in the type of root hair response observed. None of these three early
      mutants formed infection threads. Infection threads were observed in mutant sym-2
      as well as in ineffective nodules. Mutant sym-4 also formed infection threads but
      lacked nodules. The phenotypes observed for mutants from these five loci suggest
      that a secondary receptor or signal produced by the plant is required for nodule
      development.

PMID- 12231991
TI  - Identification of Distinct Internal and External Isozymes of Carbonic Anhydrase
      in Chlorella saccharophila.
AB  - External carbonic anhydrase (CA) was detected in whole cells of alkaline-grown
      Chlorella saccharophila but was suppressed by growth at acid pH or growth on
      elevated levels of CO2. Internal CA activity was measured potentiometrically as
      an increase in activity in cell extracts over that of intact cells. Cells grown
      under all conditions had equal levels of internal CA activity. Two isozymes were
      identified after electrophoretic separation of soluble proteins on cellulose
      acetate plates. The fast isozyme was found in cells grown under all conditions,
      whereas the slow isozyme was found only in cells grown at alkaline pH. Western
      blot analysis following sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      using antibodies produced against the periplasmic form of CA from Chlamydomonas
      reinhardtii revealed a single band at 39 kD, which did not change in intensity
      between growth conditions and was associated only with proteins eluted from the
      fast band. The slow isozyme was inactivated by incubation of cell extract at
      30[deg]C and by incubation in 10 mM dithiothreitol, whereas the internal form was
      unaffected. These results indicate that external and internal forms of CA differ
      in structure and their activities respond differently to environmental
      conditions.

PMID- 12231992
TI  - Oxidative Stress Affects [alpha]- Tocopherol Content in Soybean Embryonic Axes
      upon Imbibition and following Germination.
AB  - The content of [alpha]-tocopherol ([alpha]T) in isolated soybean (Glycine max,
      var Hood) embryonic axes was measured upon germination. Dry, high-vigor axes
      contained 1.2 [plus or minus] 0.1, nmol/axis and after an increase during the
      initial 6 h of imbibition, there was a decline to 1.0 [plus or minus] 0.1
      nmol/axis at 24 h of incubation. Incubation in the presence of the redox-cycling
      agent paraquat (4 mM) for 24 h increased the [alpha]T content to 1.9 [plus or
      minus] 0.2 nmol/axis. When the incubation medium was supplemented with 500 [mu]M
      Fe-EDTA over 24 h, the content of [alpha]T increased to 1.8 [plus or minus] 0.1
      nmol/axis. Isolated axes from soybean seeds stored for 56 months contained 6.5
      [plus or minus] 0.3 nmol of [alpha]T/axis after 24 h of imbibition as compared to
      1.0 [plus or minus] 0.1 nmol of [alpha]T/axis in axes from soybean seeds stored
      for 8 months. In all of these experimental situations, oxidant production as
      assessed in vivo by a fluorometric assay was increased by 4 mM paraquat (8-fold),
      500 [mu]M iron (2-fold), and 56 months of storage (4-fold) after 24 h of
      imbibition. The data presented here suggest that the cellular content of [alpha]T
      is physiologically adjusted as a response to conditions of oxidative stress.

PMID- 12231993
TI  - Casein Kinase II-Type Protein Kinase from Pea Cytoplasm and Its Inactivation by
      Alkaline Phosphatase in Vitro.
AB  - A casein kinase II-type protein kinase has been purified from the cytosolic
      fraction of etiolated pea (Pisum sativum L.) plumules to about 90% purity as
      judged from Coomassie blue stained sodium dodecyl sulfate-polyacrylamide gels.
      This kinase has a tetrameric [alpha][alpha]'[beta]2 structure with a native
      molecular mass of 150 kD, and subunit molecular masses of 41 and 40 kD for the
      two catalytic subunits ([alpha] and [alpha]') and 35 kD for the putative
      regulatory subunit ([beta]).Casein and phosvitin can be used as artificial
      substrates for this kinase. Both serine and threonine residues were
      phosphorylated when mixed casein, [beta]-casein, or phosvitin were used as the
      substrate, whereas only serine was phosphorylated if [alpha]-casein or histone
      III-S was the substrate. The kinase activity was stimulated 130% by 0.5 mM
      spermine (the concentration required for 50% of maximal enzyme activity [A50] =
      0.1 mM) and 80% by 2.5 mM spermidine (A50 = 0.4 mM), whereas putrescine and
      cadaverine had no effect. The kinase was very sensitive to inhibition by heparin
      (concentration for 50% inhibition [I50] = 0.025 [mu]g/mL). In contrast to most
      other casein kinase II-type protein kinases, this preparation was inhibited by K+
      and Na+, with I50 values of 75 and 65 mM, respectively. Pretreatment of the
      purified kinase preparation in vitro with alkaline phosphatase caused a 5-fold
      decrease in its activity. Additionally, this kinase also lost its activity when
      its [beta] subunit was autophosphorylated in the absence of substrate. These
      results suggest that the activity of this casein kinase II protein kinase may be
      regulated by the phosphorylation state of two different sites in its multimeric
      structure.

PMID- 12231994
TI  - Characterization of Paraquat Transport in Protoplasts from Maize (Zea mays L.)
      Suspension Cells.
AB  - Protoplasts isolated from maize (Zea mays L.) suspension cells were used to study
      transport of paraquat. [14C]Paraquat uptake was measured in 400-[mu]L centrifuge
      tubes using silicon oil centrifugation techniques. Approximately 50% of
      accumulation from a 100 [mu]M paraquat solution occurred in the first 10 s, and
      net accumulation reached a maximum after about 10 min. Membrane binding accounted
      for about 30% of apparent accumulation. Concentration-dependent uptake kinetics
      were characterized by a non-saturating curve, which was resolved into a linear
      and a saturable component. The Km of the saturable component was 132 [mu]M, and
      the Vmax was 0.512 nmol [mu]L of protoplasts-1 min-1. In the absence of sucrose,
      the Vmax of the saturable component was reduced by 52%, suggesting that paraquat
      uptake across the plasmalemma is energy dependent. Measurement of concentration
      dependent binding of paraquat to burst protoplasts showed a linear response. This
      suggests that the linear component from intact protoplast concentration kinetics
      represented paraquat binding to the plasmalemma surface. Calcium inhibited the
      saturable component, and this inhibition was shown by Lineweaver-Burk analysis to
      be noncompetitive. Putrescine, a divalent cationic polyamine with a charge
      distribution similar to that of paraquat, competitively inhibited paraquat
      uptake. These results show that paraquat transport characteristics at the
      plasmalemma of maize protoplasts are similar to those reported earlier for
      paraquat transport in roots of intact maize seedlings.

PMID- 12231995
TI  - Xyloglucan Endotransglycosylase Activity in Carrot Cell Suspensions during cell
      Elongation and Somatic Embryogenesis.
AB  - Xyloglucan endotransglycosylase (XET) has been proposed to contribute to cell
      elongation through wall loosening. To explore this relationship further, we
      assayed this enzyme activity in suspensions of carrot (Daucus carota L.) cells
      exhibiting various rates of cell elongation. In one cell line, elongation was
      induced by dilution into dichlorophenoxyacetic acid (2,4-D)-free medium. During
      this elongation, 93% of the XET activity was found in the culture medium; in
      nonelongating controls, by contrast, 68% was found in the cell extracts even
      though the specific activity of these extracts was lower than in the elongating
      cells. By far the highest rates of XET secretion per cell were in the elongating
      cells. A second cell line was induced to undergo somatic embryogenesis by
      dilution into 2,4-D-free medium. During the first 6 d, numerous globular
      embryoids composed of small, isodiametric cells were formed in the absence of
      cell elongation; extracellular XET activity was almost undetectable, and
      intracellular specific activity markedly declined. After 6 d, heart, torpedo, and
      cotyledonary embryoids began to appear (i.e. cell elongation resumed); the
      intracellular specific activity of XET rose rapidly and >80% of the XET activity
      accumulated in the medium. Thus, nonexpanding cell suspensions (whether or not
      they were rapidly dividing) produced and secreted less XET activity than did
      expanding cells. We propose that a XET molecule has an ephemeral wall-loosening
      role while it passes through the load-bearing layer of the wall on its way from
      the protoplast into the culture medium.

PMID- 12231996
TI  - Effect of Different Carbon Sources on Relative Growth Rate, Internal
      Carbohydrates, and Mannitol 1-Oxidoreductase Activity in Celery Suspension
      Cultures.
AB  - Little information exists concerning the biochemical route of mannitol catabolism
      in higher plant cells. In this study, the role of a recently discovered mannitol
      1-oxidoreductase (MDH) in mannitol catabolism was investigated. Suspension
      cultures of celery (Apium graveolens L. var dulce [Mill.] Pers.) were
      successfully grown on nutrient media with either mannitol, mannose, or sucrose as
      the sole carbon source. Cell cultures grown on any of the three carbon sources
      did not differ in relative growth rate, as measured by packed cell volume, but
      differed drastically in internal carbohydrate concentration. Mannitol-grown cells
      contained high concentrations of mannitol and extremely low concentrations of
      sucrose, fructose, glucose, and mannose. Sucrose-grown cells had high
      concentrations of sucrose early in the growth cycle and contained a substantial
      hexose pool. Mannose-grown cells had a high mannose concentration early in the
      cycle, which decreased during the growth cycle, whereas their internal sucrose
      concentrations remained relatively constant during the entire growth cycle.
      Celery suspension cultures on all three carbon substrates contained an NAD
      dependent MDH. Throughout the growth cycle, MDH activity was 2- to 4-fold higher
      in mannitol-grown cells compared with sucrose- or mannose-grown cells, which did
      not contain detectable levels of mannitol, indicating that MDH functions pre
      dominantly in an oxidative capacity in situ. The MDH activity observed in celery
      cells was 3-fold higher than the minimum amount required to account for the
      observed rate of mannitol utilization from the media. Cultures transferred from
      mannitol to mannose underwent a decrease in MDH activity over a period of days,
      and transfer from mannose to mannitol resulted in an increase in MDH activity.
      These data provide strong evidence that MDH plays an important role in mannitol
      utilization in celery suspension cultures.

PMID- 12231997
TI  - Current Nitrogen Fixation Is Involved in the Regulation of Nitrogenase Activity
      in White Clover (Trifolium repens L.).
AB  - Previous studies have shown that nitrogenase activity decreases dramatically
      after defoliation, presumably because of an increase in the O2 diffusion
      resistance in the infected nodules. It is not known how this O2 diffusion
      resistance is regulated. The aim of this study was to test the hypothesis that
      current N2 fixation (ongoing flux of N2 through nitrogenase) is involved in the
      regulation of nitrogenase activity in white clover (Trifolium repens L. cv
      Ladino) nodules. We compared the nitrogenase activity of plants that were
      prevented from fixing N2 (by continuous exposure of their nodulated root system
      to an Ar:O2 [80:20] atmosphere) with that of plants allowed to fix N2 (those
      exposed to N2:O2, 80:20). Nitrogenase activity was determined as the amount of H2
      evolved under Ar:O2. An open flow system was used. In experiment I, 6 h after
      complete defoliation and the continuous prevention of N2 fixation, nitrogenase
      activity was higher by a factor of 2 compared with that in plants allowed to fix
      N2 after leaf removal. This higher nitrogenase activity was associated with a
      lower O2 limitation (measured as the partial pressure of O2 required for highest
      nitrogenase activity). In experiment II, the nitrogenase activity of plants
      prevented from fixing N2 for 2 h before leaf removal showed no response to
      defoliation. The extent to which nitrogenase activity responded to defoliation
      was different in plants allowed to fix N2 and those that were prevented from
      doing so in both experiments. This leads to the conclusion that current N2
      fixation is directly involved in the regulation of nitrogenase activity. It is
      suggested that an N feedback mechanism triggers such a response as a result of
      the loss of the plant's N sink strength after defoliation. This concept offers an
      alternative to other hypotheses (e.g. interruption of current photosynthesis,
      carbohydrate deprivation) that have been proposed to explain the immediate
      decrease in nitrogenase activity after defoliation.

PMID- 12231998
TI  - Molecular Responses to Water Deficit.

PMID- 12231999
TI  - Recognition of Peroxisomes by Immunofluorescence in Transformed and Untransformed
      Tobacco Cells.
AB  - We report the visualization of peroxisomes in tobacco (Nicotiana tabacum) leaves
      using fluorescently labeled antibodies to glycolate oxidase. In transgenic
      tobacco leaves the expression of isocitrate lyase was also visualized. In dual
      probing experiments both enzymes were shown to be present together in all
      peroxisomes in transgenic tobacco leaves.

PMID- 12232000
TI  - Soybean Seed Coat Peroxidase (A Comparison of High-Activity and Low-Activity
      Genotypes).
AB  - Peroxidase activity in the seed coats of soybean (Glycine max [L.] Merr.) is
      controlled by the Ep locus. We compared peroxidase activity in cell-free extracts
      from seed coat, root, and leaf tissues of three EpEp cultivars (Harosoy 63,
      Harovinton, and Coles) to three epep cultivars (Steele, Marathon, and Raiden).
      Extracts from the seed coats of EpEp cultivars were 100-fold higher in specific
      activity than those from epep cultivars, but there was no difference in specific
      activity in crude root or leaf extracts. Isoelectric focusing of root tissue
      extracts and staining for peroxidase activity showed that EpEp cultivars had a
      root peroxidase of identical isoelectric point to the seed coat peroxidase,
      whereas roots of the epep types were lacking that peroxidase, indicating that the
      Ep locus may also affect expression in the root. In seed coat extracts,
      peroxidase was the most abundant soluble protein in EpEp cultivars, whereas this
      enzyme was present only in trace amounts in epep genotypes, as determined by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Histochemical
      localization of peroxidase activity in seed coats of EpEp cultivars shows that
      the enzyme occurs predominately in the cytoplasm of hourglass cells of the
      subepidermis. No obvious difference in the gross or microscopic structure of the
      seed coat was observed to be associated with the Ep locus. These results suggest
      that soybean seed coat peroxidase may be involved in processes other than seed
      coat biosynthesis.

PMID- 12232001
TI  - Overexpression of Superoxide Dismutase Protects Plants from Oxidative Stress
      (Induction of Ascorbate Peroxidase in Superoxide Dismutase-Overexpressing
      Plants).
AB  - Photosynthesis of leaf discs from transgenic tobacco plants (Nicotiana tabacum)
      that express a chimeric gene that encodes chloroplast-localized Cu/Zn superoxide
      dismutase (SOD+) was protected from oxidative stress caused by exposure to high
      light intensity and low temperature. Under the same conditions, leaf discs of
      plants that did not express the pea SOD isoform (SOD-) had substantially lower
      photosynthetic rates. Young plants of both genotypes were more sensitive to
      oxidative stress than mature plants, but SOD+ plants retained higher
      photosynthetic rates than SOD- plants at all developmental stages tested. Not
      surprisingly, SOD+ plants had approximately 3-fold higher SOD specific activity
      than SOD- plants. However, SOD+ plants also exhibited a 3- to 4-fold increase in
      ascorbate peroxidase (APX) specific activity and had a corresponding increase in
      levels of APX mRNA. Dehydroascorbate reductase and glutathione reductase specific
      activities were the same in both SOD+ and SOD- plants. These results indicate
      that transgenic tobacco plants that overexpress pea Cu/Zn SOD II can compensate
      for the increased levels of SOD with increased expression of the H2O2-scavenging
      enzyme APX. Therefore, the enhancement of the active oxygen-scavenging system
      that leads to increased oxidative stress protection in SOD+ plants could result
      not only from increased SOD levels but from the combined increases in SOD and APX
      activity.

PMID- 12232002
TI  - Effects of Ambient CO2 Concentration on Growth and Nitrogen Use in Tobacco
      (Nicotiana tabacum) Plants Transformed with an Antisense Gene to the Small
      Subunit of Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase.
AB  - Growth of the R1 progeny of a tobacco plant (Nicotiana tabacum) transformed with
      an antisense gene to the small subunit of ribulose-1,5-carboxylase/oxygenase
      (Rubisco) was analyzed under 330 and 930 [mu]bar of CO2, at an irradiance of 1000
      [mu]mol quanta m-2 s-1. Rubisco activity was reduced to 30 to 50% and 13 to 18%
      of that in the wild type when one and two copies of the antisense gene,
      respectively, were present in the genome, whereas null plants and wild-type
      plants had similar phenotypes. At 330 [mu]bar of CO2 all antisense plants were
      smaller than the wild type. There was no indication that Rubisco is present in
      excess in the wild type with respect to growth under high light. Raising ambient
      CO2 pressure to 930 [mu]bar caused plants with one copy of the DNA transferred
      from plasmid to plant genome to achieve the same size as the wild type at 330
      [mu]bar, but plants with two copies remained smaller. Differences in final size
      were due mostly to early differences in relative rate of leaf area expansion (m2
      m-2 d-1) or of biomass accumulation (g g-1 d-1): within less than 2 weeks after
      germination relative growth rates reached a steady-state value similar for all
      plants. Plants with greater carboxylation rates were characterized by a higher
      ratio of leaf carbon to leaf area, and at later stages, they were characterized
      also by a relatively greater allocation of structural and nonstructural carbon to
      roots versus leaves. However, these changes per se did not appear to be causing
      the long-term insensitivity of relative growth rates to variations in
      carboxylation rate. Nor was this insensitivity due to feedback inhibition of
      photosynthesis in leaves grown at high partial pressure of CO2 in the air (pa) or
      with high Rubisco activity, even when the amount of starch approached 40% of leaf
      dry weight. We propose that other intrinsic rate-limiting processes that are
      independent of carbohydrate supply were involved. Under plentiful nitrogen
      supply, reduction in the amount of nitrogen invested in Rubisco was more than
      compensated for by an increase in leaf nitrate. Nitrogen content of organic
      matter, excluding Rubisco, was unaffected by the antisense gene. In contrast, it
      was systematically lower at elevated pa than at normal pa. Combined with the
      positive effects of pa on growth, this resulted in the single-dose antisense
      plants growing as fast at 930 [mu]bar of CO2 as the wild-type plants at 330
      [mu]bar of CO2 but at a lower organic nitrogen cost.

PMID- 12232003
TI  - Effect of Severe Water Stress on Aspects of Crassulacean Acid Metabolism in
      Xerosicyos.
AB  - Xerosicyos danguyi H.Humb. (Cucurbitaceae) is a Crassulacean acid metabolism
      (CAM) species native to Madagascar. Previously, it was shown that when grown
      under good water conditions, it is a typical CAM plant, but when water stressed,
      it shifts to a dampened form of CAM, termed CAM-idling, in which stomata are
      closed day and night but with a continued, low diurnal organic acid fluctuation.
      We have now studied the kinetics of some metabolic features of the shift from CAM
      to CAM-idling under severe water stress and the recovery upon rewatering. When
      water is withheld, there is a steady decrease in relative water content (RWC),
      reaching about 50%, at which point the water potential decreases precipitously
      from about -2 or -3 bars to -12 bars. Abscisic acid (ABA) increases sharply at
      about 75% RWC. Stomata close, which limits CO2 uptake, and there is a dampened
      diurnal organic acid fluctuation typical of CAM-idling. Throughout an extended
      stress period to 50% RWC, there is no change in chlorophyll, protein, and
      ribulose bisphosphate carboxylase activity compared with the well-watered plants.
      Despite the fact that the tissue was already in CAM, the stress is accompanied by
      an increase in phosphoenolpyruvate carboxylase (PEPc) mRNA, extractable PEPc
      activity, and PEPc protein (such that the specific activity remained
      approximately constant) and a decrease in the apparent Km(PEP). It is not known
      if the changes in Km(PEP) in response to drought are related to or are separate
      from the increases in PEPc protein and mRNA. The changes in Km(PEP) could be in
      response to the decreased endogenous levels of organic acids, but evidently are
      not an assay artifact. The increases in PEPc protein and mRNA appear to be
      related to the water-stress treatment and may result from the increased
      concentration of ABA or the decreased levels of endogenous organic acids. When
      rewatered, the metabolism quickly returns to the well-watered control typical of
      CAM.

PMID- 12232004
TI  - Developmental Variability of Photooxidative Stress Tolerance in Paraquat
      Resistant Conyza.
AB  - Paraquat-resistant hairy fleabane (Conyza bonariensis L. Cronq.) has been
      extensively studied, with some contention. A single, dominant gene
      pleiotropically controls levels of oxidant-detoxifying enzymes and tolerance to
      many photooxidants, to photoinhibition, and possibly to other stresses. The weed
      forms a rosette on humid short days and flowers in dry long days and, thus, needs
      plasticity to photooxidant stresses. In a series of four experiments over 20
      months, the resistant and susceptible biotypes were cultured in constant 10-h low
      light short days at 25[deg]C. Resistance was measured as recovery from paraquat.
      The concentration required to achieve 50% inhibition of the resistant biotype was
      about 30 times that of the susceptible one just after germination, increased to
      >300 times that of the susceptibles at 10 weeks of growth, and then decreased to
      20-fold, remaining constant except for a brief increase while bolting. Resistance
      increased when plants were induced to flower by long days. The levels of plastid
      superoxide dismutase and of glutathione reductase were generally highest in
      resistant plants compared to those of the susceptibles at the times of highest
      paraquat resistance, but they were imperceptibly different from the susceptible
      type at the times of lower paraquat resistance. Photoinhibition tolerance
      measured as quantum yield of oxygen evolution at ambient temperatures was highest
      when the relative amounts of enzymes were highest in the resistant biotype.
      Resistance to photoinhibition was not detected by chlorophyll a fluorescence.
      Enzyme levels, photoinhibition tolerance, and paraquat resistance all increased
      during flowering in both biotypes. Imperceptibly small increases in enzyme levels
      would be needed for 20-fold resistance, based on the moderate enzyme increases
      correlated with 300-fold resistance. Thus, it is feasible that either these
      enzymes play a role in the first line of defense against photooxidants, or
      another, yet unknown mechanism(s) facilitate(s) the lower level of resistance, or
      the enzymes and unknown mechanisms act together.

PMID- 12232005
TI  - Kinematics and Dynamics of Sorghum (Sorghum bicolor L.) Leaf Development at
      Various Na/Ca Salinities (I. Elongation Growth).
AB  - In many salt-sensitive species, elevated concentrations of Ca in the root growth
      media ameliorate part of the shoot growth reduction caused by NaCl stress. The
      physiological mechanisms by which Ca exerts protective effects on leaf growth are
      still not understood. Understanding growth inhibition caused by a stress
      necessitates locating the leaf expansion region and quantifying the profile of
      the growth reduction. This will enable comparisons and correlations with spatial
      gradients of probable physiologically inhibiting factors. In this work we applied
      the methods of growth kinematics to analyze the effects of elevated Ca
      concentrations on the spatial and temporal distributions of growth within the
      intercalary expanding region of salinized sorghum (Sorghum bicolor [L.] Moench,
      cv NK 265) leaves. NaCl (100 mM) caused a decrease in leaf elongation rate by
      shortening the leaf growing zone by 20%, as well as reducing the peak value of
      the longitudinal relative elemental growth rate (REG rate). Increasing the Ca
      concentrations from 1 to 10 mM restored the length of the growing zone of both
      emerged and unemerged salinized leaves and increased the peak value of the REG
      rate. The beneficial effects of supplemental Ca were, however, more pronounced in
      leaves after their appearance above the whorl of encircling older leaf sheaths.
      Elevated Ca then resulted in a peak value of REG rate higher than in the
      salinized leaves. The peak value of unemerged leaves was not increased, although
      it was maintained over a longer distance. The duration of elongation growth
      associated with a cell during its displacement from the leaf base was longer in
      salinized than control leaves, despite the fact that the elongation zone was
      shorter in salinity. Although partially restoring the length of the elongation
      region, supplemental Ca had no effect on the age of cessation of growth.
      Elongation of a tissue element, therefore, ceased when a cellular element reached
      a certain age and not a specific distance from the leaf base.

PMID- 12232006
TI  - Two Sweetclover (Melilotus alba Desr.) Mutants Temperature Sensitive for
      Chlorophyll Expression.
AB  - The nonallelic sweetclover (Melilotus alba Desr.) mutants U371 (ch10/ch10
      genotype) and U372 (ch11/ch11 genotype) are derived from the U389 (+/+ genotype)
      parental strain. Growth of the U389 strain at a temperature of 17 or 26[deg]C
      results in plants normally green in appearance. The U371 and U372 mutant plants
      grown at 26[deg]C are slightly to moderately chlorophyll (Chl) deficient and have
      decreased Chl b/a ratios. Growth of the mutants at 17[deg]C results in plants
      severely deficient in Chl a, with markedly reduced levels of carotenoids except
      for violaxanthin, and with negligible amounts of Chl b or apoproteins for the
      light-harvesting complex of photosystem II. If mutant plants grown at 17[deg]C
      are transferred to 26[deg]C, during the next 20 d the amount of Chl per fresh
      weight will increase 5-fold and both the Chl b/a ratio and the expression of the
      light-harvesting complex apoproteins will progressively increase. Studies of the
      U371 mutant during the temperature-induced greening demonstrate progressive
      changes in chloroplast ultra-structure and leaf carbon isotope fractionation that
      parallel the increases in Chl. Changes observed in the leaf carbon isotope
      fractionation in the mutant suggest that, in addition to the already known
      effects of various abiotic factors, structural and metabolic internal factors can
      also influence whether the limitation in CO2 fixation is at the level of
      diffusion or carboxylation. Such temperature-initiated progressive greening in
      these and similar mutants may make them useful tools to elucidate not only the
      biosynthesis and assembly of the photosynthetic apparatus, but also physiological
      phenomena such as the influence of light-driven energy production on the overall
      carbon isotope fractionation during photosynthesis.

PMID- 12232007
TI  - Kinetics of Nodule Development in Glycine soja.
AB  - Nodule development in the interaction of Glycine soja Sieb. & Zucc. PI468.397
      with Bradyrhizobium japonicum USDA110 was studied by hypochlorite clearing and
      methylene blue staining. Even the earliest stages of nodule development could be
      observed. The entire length of the primary root was examined up to 15 d
      postinoculation. Markedly curled root hairs and the first cell divisions in the
      hypodermal layer (stage I) were observed 2 d postinoculation, and by 3 d cell
      division activity had spread to the outer layers of the cortex (stage II).
      Cortical cell division centers not associated with curled root hairs, frequently
      observed in soybean (Glycine max [L.] Merr.), were very rare in G. soja. The
      cortical cell division centers that had developed a well-defined nodule meristem
      (at or beyond stage IV) by 6 d postinoculation continued to develop, but the less
      advanced stages became arrested. Almost all nodules developed near the position
      of the root tip at the time of inoculation. In the parts of the root that
      developed after inoculation, regions with a high density of markedly curled root
      hairs per root length were observed. The percentage of the curled root hairs
      associated with cortical cell division centers, however, declined with each
      successive peak. Regulation of nodule development in G. soja was similar to that
      previously reported in soybean, although the rate of nodule development was
      slower.

PMID- 12232008
TI  - On the Function of Mitochondrial Metabolism during Photosynthesis in Spinach
      (Spinacia oleracea L.) Leaves (Partitioning between Respiration and Export of
      Redox Equivalents and Precursors for Nitrate Assimilation Products).
AB  - The functioning of isolated spinach (Spinacia oleracea L.) leaf mitochondria has
      been studied in the presence of metabolite concentrations similar to those that
      occur in the cytosol in vivo. From measurements of the concentration dependence
      of the oxidation of the main substrates, glycine and malate, we have concluded
      that the state 3 oxidation rate of these substrates in vivo is less than half of
      the maximal rates due to substrate limitation. Analogously, we conclude that
      under steady-state conditions of photosynthesis, the oxidation of cytosolic NADH
      by the mitochondria does not contribute to mitochondrial respiration.
      Measurements of mitochondrial respiration with glycine and malate as substrates
      and in the presence of a defined malate:oxaloacetate ratio indicated that about
      25% of the NADH formed in vivo during the oxidation of these metabolites inside
      the mitochondria is oxidized by a malate-oxaloacetate shuttle to serve
      extramitochondrial processes, e.g. reduction of nitrate in the cytosol or of
      hydroxypyruvate in the peroxisomes. The analysis of the products of the oxidation
      of malate indicates that in the steady state of photosynthesis the activity of
      the tricarboxylic acid cycle is very low. Therefore, we have concluded that the
      mitochondrial oxidation of malate in illuminated leaves produces mainly citrate,
      which is converted via cytosolic aconitase and NADP-isocitrate dehydrogenase to
      yield 2-oxoglutarate as the precursor for the formation of glutamate and
      glutamine, which are the main products of photosynthetic nitrate assimilation.

PMID- 12232009
TI  - Effects of Inhibitors of Protein Serine/Threonine Phosphatases on Pollination in
      Brassica.
AB  - We have examined the effect of the protein phosphatase inhibitors okadaic acid
      and microcystin on pollen-pistil interactions in Brassica. Inhibitor-treated
      flowers or floral buds were pollinated with untreated pollen and examined for
      pollen tube growth by fluorescence microscopy. Our results show that type 1 or
      type 2A serine/threonine phosphatases play a crucial role in the pollination
      responses of Brassica. We observed two distinct effects of protein phosphatase
      inhibitors on pollination: (a) the inhibition of pollen tube growth during cross
      pollination in flowers, and (b) the break-down of self-incompatibility or
      promotion of pollen tube growth during self-pollination in flower buds just prior
      to anthesis. Thus, treatment of flower pistils with protein phosphatase
      inhibitors resulted in the inhibition of pollen tube growth at the surface of the
      papillar cells of the stigma in crosses between different self-incompatible
      Brassica oleracea strains, in an interspecific cross between B. oleracea and
      Brassica campestris, and in self-pollinations of a self-fertile Brassica napus
      cultivar. With four different self-incompatibility genotypes, treatment of mature
      flowers with protein phosphatase inhibitors had no effect on self-pollination
      response. In contrast, treatment of flower buds just prior to the anthesis stage
      allowed self-pollen tube invasion of papillar cells. However, the magnitude of
      this effect was genotype dependent, being most pronounced in the S22 genotype.
      The data support the conclusion that pollinations in Brassica are controlled in
      part by the presence of phosphorylated proteins in the papillar cells of the
      stigma, and that the quantity of these proteins or their levels of
      phosphorylation changes during stigma development.

PMID- 12232010
TI  - Estimation of Bundle Sheath Cell Conductance in C4 Species and O2 Insensitivity
      of Photosynthesis.
AB  - Low conductance to CO2 of bundle sheath cells is required in C4 photosynthesis to
      maintain high [CO2] at the site of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco). Elevated [CO2] allows high CO2 assimilation
      rates by this enzyme and prevents Rubisco oxygenase activity and O2 inhibition of
      carboxylation. Bundle sheath conductance to CO2 was estimated by chemically
      inhibiting phosphoenolpyruvate carboxylase and calculating the slope of the
      linear response of leaf CO2 uptake to [CO2]. The inhibitor 3,3-dichloro-2
      dihydroxyphosphinoylmethyl-2-propenoate was supplied to detached leaves of
      Panicum maximum, Panicum miliaceum, and Sorghum bicolor at 4 mM. Uptake of CO2
      was measured at 210 mL L-1 O2 over the CO2 concentration range of 0.34 to 28 mL L
      1. Without the inhibitor, CO2 uptake increased steeply at low [CO2] and saturated
      at about 1 mL L-1. After inhibition, CO2 uptake was a linear function of [CO2]
      over much of the range tested. The slope of this CO2 response, taken as bundle
      sheath conductance, was 2.35, 1.96, and 1.13 mmol m-2 s-1 for P. maximum, P.
      miliaceum, and S. bicolor, respectively, on a leaf area basis. Conductance based
      on bundle sheath area was 0.76, 0.93, and 0.54 mmol m-2 s-1, respectively. Uptake
      of CO2 by leaves of P. maximum supplied with the inhibitor was not affected by
      reduction of [O2] from 210 to 20 mL L-1 over the range of [CO2] used. Because
      [CO2] in bundle sheath cells of inhibited leaves is likely to be much lower than
      ambient, the lack of O2 sensitivity of CO2 uptake cannot be ascribed to lack of
      O2 reaction with ribulose bisphosphate and is probably due to the low conductance
      of bundle sheath cells, especially at low ambient [CO2]. The likely result of
      reducing [O2] from 210 to 20 mL L-1 is to stimulate carboxylation of ribulose
      bisphosphate, thus further reducing [CO2] in bundle sheath cells and increasing
      CO2 diffusion to these cells from the mesophyll. However, the increase in
      diffusion is greatly limited by low conductance of the bundle sheath cell walls.
      Calculations based on estimated bundle sheath conductance show that changes in
      bundle sheath [CO2] of 0.085 to 0.5 mL L-1, which might be associated with
      reduced [O2], would have a negligible effect on CO2 uptake.

PMID- 12232011
TI  - The Interactive Effects of pH, L-Malate, and Glucose-6-Phosphate on Guard-Cell
      Phosphoenolpyruvate Carboxylase.
AB  - The interactive effects of pH, L-malate, and glucose-6-phosphate (Glc-6-P) on the
      Vmax and Km of guard-cell (GC) phosphoenolpyruvate (PEP) carboxylase (PEPC) of
      Vicia faba L. were determined. Leaves of three different physiological states
      (closed stomata, opening stomata, open stomata) were rapidly frozen and freeze
      dried. GC pairs dissected from the leaves were individually extracted and
      individually assayed for the kinetic properties of PEPC. Vmax was 6 to 9 pmol GC
      pair-1 h-1 and was apparently unaffected to a biologically significant extent by
      the investigated physiological states of the leaf, pH (7.0 or 8.5), L-malate (0,
      5, or 15 mM), and Glc-6-P (0, 0.1, 0.5, 0.7, or 5 mM). As reported earlier, the
      Km(PEP.Mg) was about 0.2 mM (pH 8.5) or 0.7 mM (pH 7.0), which can be compared
      with a GC [PEP] of 0.27 mM. In the study reported here, we determined that the in
      situ GC [Glc-6-P] equals approximately 0.6 to 1.2 mM. When 0.5 mM Glc-6-P was
      included in the GC PEPC assay mixture, the Km(PEP.Mg) decreased to about 0.1 mM
      (pH 8.5) or 0.2 mM (pH 7.0). Thus, Glc-6-P at endogenous concentrations would
      seem both to activate the enzyme and to diminish the dramatic effect of pH on
      Km(PEP.Mg). Under assay conditions, L-malate is an inhibitor of GC PEPC. In
      planta, cytoplasmic [L-malate] is approximately 8 mM. Inclusion of 5 mM L-malate
      increased the Km(PEP.Mg) to about 3.6 mM (pH 7.0) or 0.4 mM (pH 8.5). Glc-6-P
      (0.5 mM) was sufficient to relieve L-malate inhibition completely at pH 8.5. In
      contrast, approximately 5 mM Glc-6-P was required to relieve L-malate inhibition
      at pH 7.0. No biologically significant effect of physiological state of the
      tissue on GC PEPC Km(PEP.Mg) (regardless of the presence of effectors) was
      observed. Together, these results are consistent with a model that GC PEPC is
      regulated by its cytosolic chemical environment and not by posttranslational
      modification that is detectable at physiological levels of effectors. It is
      important to note, however, that we did not determine the phosphorylation status
      of GC PEPC directly or indirectly (by comparison of the concentration of L-malate
      that causes a 50% inhibition of GC PEPC).

PMID- 12232012
TI  - Regulation of Purine Metabolism in Intact Leaves of Coffea arabica.
AB  - The capacity of Coffea arabica leaves (5- x 5-mm pieces) to synthesize de novo
      and catabolize purine nucleotides to provide precursors for caffeine (1,3,7
      trimethylxanthine) was investigated. Consistent with de novo synthesis, glycine,
      bicarbonate, and formate were incorporated into the purine ring of inosine
      5[prime]-monophosphate (IMP) and adenine nucleotides ([sigma]Ade); azaserine, a
      known inhibitor of purine de novo synthesis, inhibited incorporation. Activity of
      the de novo pathway in C. arabica per g fresh weight of leaf tissue during a 3-h
      incubation period was 8 [plus or minus] 4 nmol of formate incorporated into IMP,
      61 [plus or minus] 7 nmol into [sigma]Ade, and 150 nmol into caffeine (the latter
      during a 7-h incubation). Coffee leaves exhibited classical purine catabolism.
      Radiolabeled formate, inosine, adenosine, and adenine were incorporated into
      hypoxanthine and xanthine, which were catabolized to allantoin and urea. Urease
      activity was demonstrated. Per g fresh weight, coffee leaf squares incorporated
      90 [plus or minus] 22 nmol of xanthine into caffeine in 7 h but degraded 102
      [plus or minus] 1 nmol of xanthine to allantoin in 3 h. Feedback control of de
      novo purine biosynthesis was contrasted in C. arabica and Cucurbita pepo, a
      species that does not synthesize purine alkaloids. End-product inhibition was
      demonstrated to occur in both species but at different enzyme reactions.

PMID- 12232013
TI  - Separate de Novo and Salvage Purine Pools Are Involved in the Biosynthesis of
      Theobromine but Not Caffeine in Leaves of Coffea arabica L.
AB  - In Coffea arabica leaves, the purine ring of theobromine (3,7-dimethylxanthine)
      and caffeine (1,3,7-trimethylxanthine) is provided by de novo purine
      biosynthesis: (a) [14C]glycine, [14C]bicarbonate, and [14C]formate were
      incorporated into inosine 5[prime]- monophosphate (IMP), sum of adenine
      nucleotides ([sigma]Ade), theobromine, and caffeine; and (b) incorporation of
      [14C]formate into IMP, [sigma]Ade, theobromine, and caffeine was inhibited by
      azaserine, a known inhibitor of de novo purine biosynthesis. Capacity of coffee
      leaves to salvage added purines was demonstrated by incorporation of
      [14C]hypoxanthine into [sigma]Ade and the incorporation of [14C]adenosine,
      [14C]adenine, [14C]inosine, and [14C]hypoxanthine into both theobromine and
      caffeine. Consistent with synthesis of theobromine from two separate purine
      nucleotide pools, one synthesized de novo and one via salvage, added xanthine
      5[prime]-monophosphate (XMP), inosine, or hypoxanthine failed to reduce the
      incorporation of [14C]formate into theobromine but diluted the specific
      radioactivity of [14C]adenosine and [14C]adenine incorporated into theobromine.
      Evidence that theobromine is not the immediate precursor of caffeine is provided:
      (a) [14C]xanthine was incorporated into caffeine but not into theobromine; (b)
      exogenous xanthine diluted the specific radioactivity of caffeine synthesized
      from [14C]adenine and [14C]hypoxanthine but caused accumulation of radiolabel in
      theobromine; (c) allopurinol, a known inhibitor of the conversion of hypoxanthine
      to xanthine, reduced incorporation of [14C]adenine and [14C]hypoxanthine into
      caffeine but caused accumulation of radiolabel in theobromine; and (d)
      incorporation of [14C]formate into caffeine, but not into theobromine, was
      reduced by added XMP, inosine, or hypoxanthine.

PMID- 12232014
TI  - Membrane-Associated and Soluble Lipoxygenase Isoforms in Tomato Pericarp
      (Characterization and Involvement in Membrane Alterations).
AB  - Membrane-associated and soluble lipoxygenases from green tomato (Lycopersicon
      esculentum Mill. cv Ailsa Craig) fruit have been identified. Microsomal
      lipoxygenase was localized partly in the plasma membrane and tonoplast fractions.
      The possibilities of glycosyl-phosphatidylinositol or transmembrane polypeptide
      anchors in the membrane were ruled out by differential solubilization and
      temperature-induced phase separation in Triton X-114. High performance liquid
      chromatography of reaction products combined with polarography showed that tomato
      lipoxygenase is capable of specific oxygenation of fatty acids esterified in
      phospholipids. This possibility of direct action on membrane phospholipids
      strengthened the hypothesis of a role for lipoxygenase in plant senescence and
      membrane turnover. Membrane-associated lipoxygenase is polymorphic, with two
      forms differing by their isoelectric points (pls) (around 4.2 and 5.1). The pl of
      the soluble lipoxygenase corresponds to the minor microsomal enzyme, with a pl of
      5.1. The charge-differing isoforms were separated and analyzed by western
      blotting using anti-soybean lipoxygenase antibodies. A single polypeptide with an
      apparent molecular weight of 92,000 was identified in each case for the soluble
      and microsomal enzymes. It is suggested that a charge modification of the soluble
      lipoxygenase allows its association with the membrane.

PMID- 12232015
TI  - Phytotoxicity of Acetohydroxyacid Synthase Inhibitors Is Not Due to Accumulation
      of 2-Ketobutyrate and/or 2-Aminobutyrate.
AB  - Acetohydroxyacid synthase (AHAS) is the site of action of herbicides of different
      chemical classes, such as imidazolinones, sulfonylureas, and triazolopyrimidines.
      Inhibition of AHAS causes the accumulation of 2-ketobutyrate (2-KB) and 2
      aminobutyrate (2-AB) (the transamination product of 2-KB), and it has been
      proposed that the phytotoxicity of these inhibitors is due to this accumulation.
      Experiments were done to determine the relationship between accumulation of 2-KB
      and 2-AB and the phytotoxicity of imazaquin to maize (Zea mays). Imazaquin
      concentrations that inhibit growth of maize plants also cause the accumulation of
      2-KB and 2-AB in the shoots. Supplementation of imazaquin-treated plants with
      isoleucine reduced the pools of 2-KB and 2-AB in the plant but did not protect
      plants from the growth inhibitory effects of imazaquin. Conversely, feeding 2-AB
      to maize plants increased 2-KB and 2-AB pools to much higher levels than those
      observed in imazaquin-treated plants, yet such high pools of 2-KB and 2-AB in the
      plant had no significant effect on growth. These results conclusively demonstrate
      that growth inhibition following imazaquin treatment is not due to accumulation
      of 2-KB and/or 2-AB in plants. Changes in the amino acid profiles after treatment
      with imazaquin suggest that starvation for the branched-chain amino acids may be
      the primary cause of growth retardation of maize.

PMID- 12232016
TI  - Water Relation Alterations Observed during Hypersensitive Reaction Induced by
      Bacteria.
AB  - Upon exposure to pathogenic bacteria, resistant and nonhost plants undergo a
      hypersensitive reaction (HR) that is expressed as rapid plant cell death. If
      sufficient concentrations of these bacteria are inoculated to such plant tissue,
      then that portion of the tissue rapidly collapses and becomes necrotic. As the
      tissue collapses the water relations of inoculated tissues become markedly
      disturbed. We measured a decline in the relative water content (RWC) in the leaf
      like cotyledons of cotton (Gossypium hirsutum cv Immune 216) within the first 4 h
      (cut at 1 h) after inoculation with Pseudomonas syringae pv tabaci. However, the
      decrease in RWC was not caused by a decrease in initial fresh weight but by
      increased water uptake during incubation in water. By 8 h after inoculation,
      cotyledons still on the plant had lost turgidity, and their area decreased. K+
      efflux was also observed concurrently with the decrease in RWC, providing a
      reason for the loss of turgidity in the tissue. These observations suggest that
      cells lose turgor and change shape from cylinders with large intercellular spaces
      to those of a more tabular shape. During this change cell walls come closer
      together, providing an avenue for increased water uptake through capillary
      action. The stomatal diffusive resistance of intact cotyledons increased; hence,
      water loss through stomata is not the cause of the observed wilting and RWC
      decline. An increase in K+ per dry weight suggests that phloem loading or
      movement may also be impaired during bacterially induced HR.

PMID- 12232017
TI  - Ammonium Uptake by Rice Roots (I. Fluxes and Subcellular Distribution of 13NH4+).
AB  - The time course of 13NH4+ uptake and the distribution of 13NH4+ among plant parts
      and subcellular compartments was determined for 3-week-old rice (Oryza sativa L.
      cv M202) plants grown hydroponically in modified Johnson's nutrient solution
      containing 2,100, or 1000 [mu]M NH4+ (referred to hereafter as G2, G100, or G1000
      plants, respectively). At steady state, the influx of 13NH4+ was determined to be
      1.31, 5.78, and 10.11 [mu]mol g-1 fresh weight h-1, respectively, for G2, G100,
      and G1000 plants; efflux was 11, 20, and 29%, respectively, of influx. The NH4+
      flux to the vacuole was calculated to be between 1 and 1.4 [mu]mol g-1 fresh
      weight h-1. By means of 13NH4+ efflux analysis, three kinetically distinct phases
      (superficial, cell wall, and cytoplasm) were identified, with t1/2 for 13NH4+
      exchange of approximately 3 s and 1 and 8 min, respectively. Cytoplasmic [NH4+]
      was estimated to be 3.72, 20.55, and 38.08 mM for G2, G100, and G1000 plants,
      respectively. These concentrations were higher than vacuolar [NH4+], yet 72 to
      92% of total root NH4+ was located in the vacuole. Distributions of newly
      absorbed 13NH4+ between plant parts and among the compartments were also
      examined. During a 30-min period G100 plants metabolized 19% of the influxed
      13NH4+. The remainder (81%) was partitioned among the vacuole (20%), cytoplasm
      (41%), and efflux (20%). Of the metabolized 13N, roughly one-half was
      translocated to the shoots.

PMID- 12232018
TI  - Ammonium Uptake by Rice Roots (II. Kinetics of 13NH4+ Influx across the
      Plasmalemma).
AB  - Short-term influxes of 13NH4+ were measured in intact roots of 3-week-old rice
      (Oryza sativa L. cv M202) seedlings that were hydroponically grown at 2, 100, or
      1000 [mu]M NH4+. Below 1 mM external concentration ([NH4+]0), influx was
      saturable and due to a high-affinity transport system (HATS). For the HATS, Vmax
      values were negatively correlated and Km values were positively correlated with
      NH4+ provision during growth and root [NH4+]. Between 1 and 40 mM [NH4+]0, 13NH4+
      influx showed a linear response due to a low-affinity transport system (LATS).
      The 13NH4+ influxes by the HATS, and to a lesser extent the LATS, are energy
      dependent processes. Selected metabolic inhibitors reduced influx of the HATS by
      50 to 80%, but of the LATS by only 31 to 51%. Estimated values for Q10 (the ratio
      of rates at temperatures differing by 10[deg]C) for HATS were greater than 2.4 at
      root temperatures from 5 to 10[deg]C and were constant at approximately 1.5
      between 5 and 30[deg]C for the LATS. Influx of 13NH4+ by the HATS was insensitive
      to external pH in the range from 4.5 to 9.0, but influx by the LATS declined
      significantly beyond pH 6.0. The data presented are discussed in the context of
      the kinetics, energy dependence, and the regulation of ammonium influx.

PMID- 12232019
TI  - Choline Synthesis in Spinach in Relation to Salt Stress.
AB  - Choline metabolism was examined in spinach (Spinacia oleracea L.) plants growing
      under nonsaline and saline conditions. In spinach, choline is required for
      phosphatidylcholine synthesis and as a precursor for the compatible osmolyte
      glycine betaine (betaine). When control (nonsalinized) leaf discs were incubated
      for up to 2 h with [1,2-14C]ethanolamine, label appeared in the N-methylated
      derivatives of phosphoethanolamine including phosphomono-, phosphodi-, and
      phosphotri- (i.e. phosphocholine) methyl-ethanolamine, as well as in choline and
      betaine, whereas no radioactivity could be detected in the mono- and dimethylated
      derivatives of the free base ethanolamine. Leaf discs from salinized plants
      showed the same pattern of labeling, although the proportion of label that
      accumulated in betaine was almost 3-fold higher in the salinized leaf discs.
      Enzymes involved in choline metabolism were assayed in crude leaf extracts of
      plants. The activites of ethanolamine kinase and of the three S
      adenosylmethionine:phospho-base N-methyltransferase enzymes responsible for N
      methylating phosphoethanolamine to phosphocholine were all higher in extracts of
      plants salinized step-wise to 100, 200, or 300 mM NaCI compared with controls. In
      contrast, choline kinase, phosphocholine phosphatase, and cytidine 5[prime]
      triphosphate: phosphocholine cytidylyltransferase activities showed little
      variation with salt stress. Thus, the increased diversion of choline to betaine
      in salt-stressed spinach appears to be mediated by the increased activity of
      several key enzymes involved in choline biosynthesis.

PMID- 12232020
TI  - Ectopic Overexpression of Asparagine Synthetase in Transgenic Tobacco.
AB  - Here, we monitor the effects of ectopic overexpression of genes for pea
      asparagine synthetase (AS1) in transgenic tobacco (Nicotiana tabacum). The AS
      genes of pea and tobacco are normally expressed only during the dark phase of the
      diurnal growth cycle and specifically in phloem cells. A hybrid gene was
      constructed in which a pea AS1 cDNA was fused to the cauliflower mosaic virus 35S
      promoter. The 35S-AS1 gene was therefore ectopically expressed in all cell types
      in transgenic tobacco and constitutively expressed at high levels in both the
      light and the dark. Northern analysis demonstrated that the 35S-AS1 transgene was
      constitutively expressed at high levels in leaves of several independent
      transformants. Furthermore, amino acid analysis revealed a 10- to 100-fold
      increase in free asparagine in leaves of transgenic 35S-AS1 plants (construct
      z127) compared with controls. Plant growth analyses showed increases (although
      statistically insignificant) in growth phenotype during the vegetative stage of
      growth in 35S-AS1 transgenic lines. The 35S-AS1 construct was further modified by
      deletion of the glutamine-binding domain of the enzyme (gln[delta]AS1; construct
      z167). By analogy to animal AS, we reasoned that inhibition of glutamine
      dependent AS activity might enhance the ammonia-dependent AS activity. The 3- to
      19-fold increase in asparagine levels in the transgenic plants expressing
      gln[delta]AS1 compared with wild type suggests that the novel AS holoenzyme
      present in the transgenic plants (gln[delta]AS1 homodimer) has enhanced ammonia
      dependent activity. These data indicate that manipulation of AS expression in
      transgenic plants causes an increase in nitrogen assimilation into asparagine,
      which in turn produces effects on plant growth and asparagine biosynthesis.

PMID- 12232021
TI  - DNA Replication-Dependent Histone H2A mRNA Expression in Pea Root Tips.
AB  - Histone H2A mRNA is selectively expressed in scattered subpopulations of cells in
      the pea (Pisum sativum) root apical meristem. To study whether this specific
      expression was associated with the cell cycle, a double-labeling technique was
      used to identify cells replicating DNA during S phase and those expressing H2A
      mRNA. Cells in S phase were detected by [3H]thymidine incorporation and
      autoradiography, whereas cells containing H2A mRNA were identified by in situ
      hybridization using digoxigenin-labeled probes. Approximately 92% of the
      [3H]thymidine-labeled S-phase cells expressed H2A mRNA and 85% of cells that
      expressed H2A mRNA were in S phase. In root tissue located basal to the
      promeristem, synchronous co-located expression was observed in scattered packets
      of proliferating cells. Furthermore, neither H2A mRNA nor S-phase cells could be
      detected within the quiescent center or mature root cap. When DNA synthesis was
      inhibited with hydroxyurea, a commensurate and specific decrease in steady-state
      levels of H2A mRNA was found. We conclude that cell-specific expression of pea
      histone H2A mRNA is replication dependent and that H2A mRNA is transiently
      accumulated during a period of the cell cycle that mostly overlaps the S phase.
      We propose that the overlap between H2A expression and S phase could occur if H2A
      mRNA accumulation began in late G1 and abated in late S.

PMID- 12232022
TI  - Salt Stress Perception and Plant Growth Regulators in the Halophyte
      Mesembryanthemum crystallinum.
AB  - We selected indicators of four different metabolic processes (Crassulacean acid
      metabolism [CAM], amino acid and nitrogen mobilization metabolism,
      osmoprotection, and plant defense mechanisms) to study the relationship between
      salt-stress-mediated and plant growth regulator (PGR)-induced responses in
      Mesembryanthemum crystallinum (ice plant). Nacl and PGRs (cytokinin and abscisic
      acid [ABA]) are efficient elicitors of the well-studied Nacl stress responses:
      induction of the CAM form of phosphoenolpyruvate carboxylase, proline pinitol
      accumulation, and the increase of an osmotin-like protein. NaCl and cytokinin are
      more effective than ABA in stimulating accumulation of proline and an osmotin
      like protein before the plants are committed to flowering. The results are
      consistent with a plant defense-induction model, in which environmental stress
      and PGRs are distinct signals whose subsequent effects lead to overlapping
      responses, the magnitude of which depends on plant developmental status.

PMID- 12232023
TI  - Increased Zinc Tolerance in Silene vulgaris (Moench) Garcke Is Not Due to
      Increased Production of Phytochelatins.
AB  - The concentration of acid-soluble thiols other than reduced glutathione (SH -
      GSH) increases in the roots of zinc-sensitive and zinc-tolerant Silene vulgaris
      (Moench) Garcke after exposure to zinc for 1 to 3 d. The concentration of SH -
      GSH in the roots is higher in the sensitive plants than in the tolerant ones,
      both at equal external zinc concentrations and at zinc concentrations causing the
      same level of root-length growth inhibition. High performance liquid
      chromatography analyses show that the increase in the concentration of SH - GSH
      is not only due to the production of phytochelatins, but is also due to an
      increase in the concentration of cysteine and the production of nonidentified
      thiols. The cysteine concentration increases equally in the roots of sensitive
      and tolerant plants. The accumulation of phytochelatins is higher in the roots of
      the sensitive plants, whereas the chain length distribution of phytochelatins is
      the same in sensitive and tolerant plants. It is concluded that increased zinc
      tolerance in S. vulgaris is not due to increased production of phytochelatins.

PMID- 12232024
TI  - Synergistic Enhancement of the Antifungal Activity of Wheat and Barley Thionins
      by Radish and Oilseed Rape 2S Albumins and by Barley Trypsin Inhibitors.
AB  - Although thionins and 2S albumins are generally considered as storage proteins,
      both classes of seed proteins are known to inhibit the growth of pathogenic
      fungi. We have now found that the wheat (Triticum aestivum L.) or barley (Hordeum
      vulgare L.) thionin concentration required for 50% inhibition of fungal growth is
      lowered 2- to 73-fold when combined with 2S albumins (at sub- or noninhibitory
      concentrations) from radish (Raphanus sativus L.) or oilseed rape (Brassica napus
      L.). Furthermore, the thionin antifungal activity is synergistically enhanced (2-
      to 33-fold) by either the small subunit or the large subunit of the radish 2S
      albumins. Three other 2S albumin-like proteins, the barley trypsin inhibitor and
      two barley Bowman-Birk-type trypsin inhibitor isoforms, also act synergistically
      with the thionins (2- to 55-fold). The synergistic activity of thionins combined
      with 2S albumins is restricted to filamentous fungi and to some Gram-positive
      bacteria, whereas Gram-negative bacteria, yeast, cultured human cells, and
      erythrocytes do not show an increased sensitivity to thionin/albumin combinations
      (relative to the sensitivity to the thionins alone). Scanning electron microscopy
      and measurement of K+ leakage from fungal hyphae revealed that 2S albumins have
      the same mode of action as thionins, namely the permeabilization of the hyphal
      plasmalemma. Moreover, 2S albumins and thionins act synergistically in their
      ability to permeabilize fungal membranes.

PMID- 12232025
TI  - Role of Expansin in Cell Enlargement of Oat Coleoptiles (Analysis of
      Developmental Gradients and Photocontrol).
AB  - Expansins are wall proteins that mediate a type of acid-induced extension in
      isolated plant cell walls (S. McQueen-Mason, D.M. Durachko, D.J. Cosgrove [1992]
      Plant Cell 4: 1425-1433). To assess the role of these proteins in the process of
      cell enlargement in living tissues, we compared the spatial and temporal growth
      patterns of oat (Avena sativa L.) coleoptiles with four wall properties related
      to expansin action. These properties were (a) the ability of isolated walls and
      living segments to extend in acidic buffer, (b) the ability of heat-inactivated
      walls to extend upon application of expansins, (c) the amount of immunologically
      detectable expansin in wall protein extracts, and (d) the extractable expansin
      activity of walls. Growth rate was maximal in the apical half of dark-grown
      coleoptiles and negligible in the basal region. This growth pattern correlated
      with properties a and b; in contrast, the amount and activity of extractable
      expansin (properties c and d) were reduced only in the most basal region. Upon
      exposure to white light, coleoptiles abruptly ceased elongation at 8 to 10 h
      after start of irradiation, and this cessation correlated with reductions in
      properties a to c. The growth cessation at 8 to 10 h also coincided with the loss
      of growth response to exogenous auxin and fusicoccin in excised coleoptile
      segments. These results lend correlative support to the hypothesis that expansin
      action is important for growth responses of living oat coleoptiles (e.g.
      responses to acidic buffers, auxin, fusicoccin, aging, and light). Our results
      suggest that changes in the susceptibility of the wall to expansin action, rather
      than changes in expansin activity, may be a key determinant of the growth
      patterns in oat coleoptiles.

PMID- 12232026
TI  - Effect of Iron Deficiency on the Respiration of Sycamore (Acer pseudoplatanus L.)
      Cells.
AB  - The effects of iron deficiency on cell culture growth, cell respiration,
      mitochondrial oxidative properties, and the electron transport chain were studied
      with suspension-cultured sycamore (Acer pseudoplatanus L.) cells. Iron
      deprivation considerably decreased the initial growth rates and limited the
      maximum density of the cells. Under these conditions, the cells remained swollen
      throughout their growth. The absence of iron led to a steady decline in the
      uncoupled rate of O2 consumption. When the uncoupled rate of O2 uptake closely
      approximated the respiratory rate, the cells began to collapse. At this stage,
      the level of all the cytochromes and electron paramagnetic resonance-detectable
      Fe-S clusters of the mitochondrial inner membrane were dramatically decreased.
      Nevertheless, it appeared from substrate oxidation measurements that this overall
      depletion in iron-containing components solely disturbed the functioning of
      complex II, whereas neither complexes I, III, or IV, nor the machinery involved
      in ATP synthesis, was apparently impaired in iron-deficient mitochondria.
      However, our results suggest that the impairment of complex II resulted in a
      strong reduction of the overall capacity of the mitochondrial electron transport
      chain, which was responsible for determining the rate of endogenous respiration
      in sycamore cells. Finally, this situation led to a depletion of various energy
      metabolites that could contribute to the premature cell death.

PMID- 12232027
TI  - Sorbitol as the Primary Carbon Source for the Growth of Embryogenic Callus of
      Maize.
AB  - The effects of various carbon sources on initiation and maintenance of
      embryogenic callus of maize (Zea mays L.) and on the regeneration of plants from
      embryogenic callus were studied. Growth of embryogenic callus tissue on media
      containing sucrose was typified by the subsequent growth of both embryogenic
      (regenerable) and nonembryogenic (nonregenerable) callus. Growth of embryogenic
      callus on sorbitol was unique among the carbon sources tested in that sorbitol
      supported the subsequent growth of only embryogenic callus. Further experiments
      demonstrated that embryogenic callus grown on sorbitol had a greater regenerative
      capacity (more plants produced per gram fresh weight of callus) than callus grown
      on sucrose. Sorbitol dehydrogenase was detected in embryogenic callus of maize at
      a specific activity roughly equivalent to that found in zygotic embryos of
      developing seeds. Nonembryogenic callus did not contain significant levels of
      sorbitol dehydrogenase activity.

PMID- 12232028
TI  - Methyl Jasmonate Induces Papain Inhibitor(s) in Tomato Leaves.
AB  - Leaves of 18- to 24-d-old tomato (Lycopersicon esculentum) plants exposed to
      gaseous methyl jasmonate (MJ) for 24 h at 30[deg]C in continuous light contained
      high levels of soluble protein that inhibited papain. Chromatographic analysis
      demonstrated that the active protein had a molecular mass of 80 to 90 kD.
      Induction of papain inhibitor was directly related to the concentration of air
      borne MJ up to a maximum of 0.1 [mu]L MJ per treatment and depended on the
      duration of exposure up to 18 h. Inhibitor activity in plants treated for less
      than 18 h increased with time after treatment. Levels remained constant for up to
      4 d after treatment, after which time activity decreased. The youngest leaf, leaf
      5, consistently lost activity at a faster rate than older, lower leaves.
      Inhibitor concentration in all leaves was reduced to minimum levels by 11 d after
      MJ treatment, but did not return to control levels. Treatment with MJ in the dark
      did induce inhibitor activity, but at a significantly lower rate. Polyclonal
      antibodies raised to purified potato tuber skin cysteine proteinase inhibitors
      (CPI) cross-reacted with the tomato inhibitor, suggesting that the tomato papain
      inhibitor and the potato CPI are closely related. No papain inhibitor activity
      was observed in extracts from wounded tomato leaves, nor was there any
      immunoreactivity with antibodies raised to potato tuber skin CPI.

PMID- 12232029
TI  - Biochemical Evidence for the Role of the Waxy Protein from Pea (Pisum sativum L.)
      as a Granule-Bound Starch Synthase.
AB  - Proteins were solubilized from starch extracted from developing pea (Pisum
      sativum L.) embryos and chromatography of these proteins on a Mono-Q column
      separated two peaks of starch synthase activity. The major activity peak
      comprised more than 80% of the total activity. This fraction contained only the
      Waxy protein, as shown by polyacrylamide gel electrophoresis in the presence of
      sodium dodecyl sulfate followed by staining for proteins or by immunoblot. A 77
      kD polypeptide associated with the starch granules and presumed by others to be a
      starch synthase could not be detected in any of the active fractions. The native
      molecular weight of the solubilized starch synthase was 59,600 [plus or minus]
      1700 as determined by sucrose density gradient. It is concluded that in pea seeds
      the Waxy protein and the starch synthase bound to the granule are the same
      protein.

PMID- 12232030
TI  - Long-Distance Water Transport in Aquatic Plants.
AB  - Acropetal mass flow of water is demonstrated in two submerged angiosperms,
      Lobelia dortmanna L. and Sparganium emersum Rehman by means of guttation
      measurements. Transpiration is absent in truly submerged plants, but the presence
      of guttation verifies that long-distance water transport takes place. Use of
      tritiated water showed that the water current arises from the roots, and the main
      flow of water is channeled to the youngest leaves. This was confirmed by
      measurement of guttation, which showed the highest rates in young leaves.
      Guttation rates were 10-fold larger in the youngest leaf of S. emersum (2.1 [mu]L
      leaf-1 h-1) compared with the youngest leaf of L. dortmanna (0.2 [mu]L leaf-1 h
      1). This is probably due to profound species differences in the hydraulic
      conductance (2.7 x 10-17 m4 Pa-1 s-1 for S. emersum and 1.4 x 10-19 m4 Pa-1 s-1
      for L. dortmanna). Estimates derived from the modified Hagen-Poiseuille equation
      showed that the maximum flow velocity in xylem vessels was 23 to 84 cm h-1, and
      the required root pressure to drive the flow was small compared to that commonly
      found in terrestrial plants. In S. emersum long-distance transport of water was
      shown to be dependent on energy conversion in the roots. The leaves ceased to
      guttate when the roots were cooled to 4[deg]C from the acclimatization level at
      15[deg]C, whereas the guttation was stimulated when the temperature was increased
      to 25[deg]C. Also, the guttation rate decreased significantly when vanadate was
      added to the root medium. The observed water transport is probably a general
      phenomenon in submerged plants, where it can act as a translocation system for
      nutrients taken up from the rich root medium and thereby assure maximum growth.

PMID- 12232031
TI  - Juvenile-Specific Localization and Accumulation of a Rhamnosyltransferase and Its
      Bitter Flavonoid in Foliage, Flowers, and Young Citrus Fruits.
AB  - 1-2-Rhamnosyltransferase catalyzes the production of disaccharide-flavonoids that
      accumulate to 75% of dry weight. Vast energy is expended in a short time span to
      produce these flavonoids. The highest rhamnosyltransferase activities and
      immunodetected concentrations were observed in early development of Citrus
      grandis (pummelo), coinciding with up to 13% of fresh weight as naringin. The
      concentration of naringin in leaves, petals, receptacles, filaments, albedo, and
      flavedo drops drastically during development and correlates directly with a
      decrease in the activity and amounts of 1-2-rhamnosyltransferase. Anthers had
      minute rhamnosyltransferase activities and low concentrations of naringin.
      Conversely, high 1-2-rhamnosyltransferase activity and naringin concentrations
      appeared in both young and mature ovaries, as well as in young fruits. The total
      amounts of naringin in mature leaves decreased without detectable in vitro
      degradation of naringin in leaves. There was still a net accumulation of naringin
      in the albedo and flavedo of older fruit even though these tissues had only
      traces of 1-2-rhamnosyltransferase. Traces of enzyme synthesis in fruits, or
      import of the product from leaves, may explain the net accumulation of naringin
      in growing fruits. Unlike the late-expressed genes for glycosyltransferases in
      anthocyanin biosynthesis, the rhamnosyltransferases from Citrus are active only
      in juvenile stages of development.

PMID- 12232032
TI  - Molecular Responses to Photooxidative Stress in Pinus sylvestris (L.) (II.
      Differential Expression of CuZn-Superoxide Dismutases and Glutathione Reductase.
AB  - The influence of photooxidative stress on genes expressing superoxide dismutase
      (Sod) and glutathione reductase (Gor) was analyzed in needles of top and side
      shoots of 3-year-old Pinus sylvestris (L.) seedlings. The study was carried out
      in the field during spring recovery. From mid-April the top shoots of seedlings
      protruded above the snow and thus were exposed to sunlight, whereas the side
      shoots were covered with snow until May 4. Needles were sampled from top and side
      shoots on five different occasions. At the beginning of May the mRNA levels for
      cytosolic CuZn-Sod were significantly higher in top-shoot needles than in side
      shoot needles. Similar results were obtained for chloroplastic CuZn-Sod mRNA.
      After May 6 we could not detect any significant differences between top- and side
      shoot needles for either CuZn-Sod mRNA level. Transcript accumulation for the
      chloroplastic CuZn-Sod was up to 4-fold higher than for cytosolic CuZn-Sod in
      both types of shoots. On June 1 minimum transcript levels were observed for both
      CuZn-SOD isoforms. Protein activity analysis for CuZn-SOD isozymes did not reveal
      any significant differences between top- and side-shoot needles during the whole
      period of measurements. The mRNA level for chloroplastic Gor was similar in both
      types of shoots. However, the total GR activity was significantly higher in top
      shoot needles than in side-shoot needles at the beginning of May. The analysis of
      mRNA accumulation for chloroplastic CuZn-Sod and Gor indicates that transcript
      levels were at least 5- to 20-fold higher for CuZn-Sod than for chloroplastic
      Gor. The differential expressions of Sod and Gor genes are discussed in relation
      to regulation of the enzymic scavenging system during photooxidative stress
      conditions.

PMID- 12232033
TI  - Purification of Potato Leaf Plasma Membrane Protein pp34, a Protein
      Phosphorylated in Response to Oligogalacturonide Signals for Defense and
      Development.
AB  - A potato (Solanum tuberosum L.) plasma membrane protein called pp34, the only
      known example of a plasma membrane protein that is phosphorylated specifically in
      response to defined Oligogalacturonide signals in plants, has been purified to
      apparent homogeneity. Polyclonal antibodies raised in rabbits against the
      purified pp34 protein immunoprecipitated a single thiophosphorylated protein
      species from potato plasma membranes, as analyzed by two-dimensional denaturing
      electrophoresis and fluorography. The pp34 antibodies also recognized a single
      protein in tomato (Lycopersicon esculentum L.) membranes that is
      thiophosphorylated in response to Oligogalacturonide elicitors, as demonstrated
      by western blotting and specific immunoprecipitation. These experiments confirm
      the identity of the tomato membrane protein as a pp34 homolog and establish the
      high monospecificity of the pp34 antibodies. This will permit further
      investigation of the role of protein phosphorylation in oligouronide signaling
      for defensive genes in potato and tomato plants.

PMID- 12232034
TI  - Xyloglucan Endotransglycosylase Activity Increases during Kiwifruit (Actinidia
      deliciosa) Ripening (Implications for Fruit Softening).
AB  - The activity of xyloglucan endotransglycosylase (XET) was as-sayed in three
      tissue zones of kiwifruit (Actinidia deliciosa [A. Chev.] C.F. Liang et A.R.
      Ferguson var deliciosa cv Hayward) at harvest and at several softening stages
      following a postharvest ethylene treatment. At harvest, extractable XET activity
      per unit fresh weight in the inner pericarp (IP) and core tissue was 4.5 and 42
      times higher, respectively, than in the outer pericarp (OP). Within 24 h of
      ethylene treatment there was an increase in the activity and specific activity of
      XET in all tissues that continued throughout softening. Activity increased most
      in the OP, where it showed a 12-fold rise 6 d after ethylene treatment compared
      with 4.5- and 2.5-fold increases in the IP and core tissues, respectively.
      Visible swelling of the cell wall in each tissue was observed 24 h after the
      first detectable rise in XET activity and was most pronounced in the OP, which
      showed the greatest percentage increase in XET activity. Xyloglucan,
      galactoglucomannan, and cell wall materials isolated and purified from kiwifruit
      OP were tested as donor substrates for kiwifruit XET. The enzyme showed activity
      against xyloglucan but was inactive against galactoglucomannan. XET was active
      against cell wall materials from unripe and ripe fruit, with swollen walls from
      the latter being the better substrate. The results indicate that XET may have a
      key role early in fruit ripening, loosening the cell wall in preparation for
      further modification by other cell wall-associated enzymes.

PMID- 12232035
TI  - The Xanthophyll Cycle, Protein Turnover, and the High Light Tolerance of Sun
      Acclimated Leaves.
AB  - Changes in photosynthesis rate and photochemical characteristics in response to
      high irradiance, followed by recovery at low irradiance, were determined in four
      groups of sun-acclimated leaves of spinach (Spinacia oleracea L.). These four
      groups were untreated control leaves, leaves treated with either an inhibitor of
      energy dissipation associated with the xanthophyll cycle (dithiothreitol, DTT) or
      an inhibitor of chloroplast-encoded protein synthesis (chloramphenicol, CAP), as
      well as leaves treated with a combination of DTT + CAP. In these sun leaves,
      treatment with either CAP or DTT alone did not result in an inhibition of the
      recovery from high-light-induced decreases in photochemical efficiency. Only the
      treatment with a combination of CAP + DTT caused a strong and irreversible
      depression of photochemical efficiency. We suggest that in the presence of DTT
      (and in the absence of xanthophyll cycle-associated energy dissipation), protein
      turnover may be involved in the recovery process. We further suggest that the
      reversible depression of photochemical efficiency in CAP-treated sun leaves
      reflects xanthophyll cycle-associated energy dissipation. In the leaves treated
      with CAP + DTT a slowly developing decrease in the maximal yield of chlorophyll
      fluorescence in high light may indicate an alternative, xanthophyll cycle
      independent dissipation process in the photochemical system. Moreover, CAP
      treatments did not cause any changes in the deepoxidation state of the
      xanthophyll cycle. However, CAP-treated leaves, but not those treated with CAP +
      DTT, exhibited some decrease in the pool size of the xanthophyll cycle during the
      exposure to high light.

PMID- 12232036
TI  - Sphingolipid Long-Chain Base Synthesis in Plants (Characterization of Serine
      Palmitoyltransferase Activity in Squash Fruit Microsomes).
AB  - The activity of serine palmitoyltransferase (palmitoyl-coenzyme A [CoA]:L-serine
      [Ser]-C-palmitoyltransferase [decarboxylating], EC 2.3.1.50), the enzyme
      catalyzing the first step in the synthesis of the long-chain base required for
      sphingolipid assembly, has been characterized in a plant system. Enzyme activity
      in a microsomal membrane fraction from summer squash fruit (Cucurbita pepo L. cv
      Early Prolific Straightneck) was assayed by monitoring the incorporation of L
      [3H]Ser into the chloroform-soluble product, 3-ketosphinganine. Addition of NADPH
      to the assay system resulted in the conversion of 3-ketosphinganine to
      sphinganine. The apparent Km for Ser was approximately 1.8 mM. The enzyme
      exhibited a strong preference for palmitoyl-CoA, with optimal activity at a
      substrate concentration of 200 [mu]M. Pyridoxal 5[prime]-phosphate was required
      as a coenzyme. The pH optimum was 7.6, and the temperature optimum was 36 to
      40[deg]C. Enzyme activity was greatest in the microsomal fraction obtained by
      differential centrifugation and was localized to the endoplasmic reticulum using
      marker enzymes. Two known mechanism-based inhibitors of the mammalian enzyme, L
      cycloserine and [beta]-chloro-L-alanine, were effective inhibitors of enzyme
      activity in squash microsomes. Changes in enzyme activity with size (age) of
      squash fruit were observed. The results from this study suggest that the
      properties and catalytic mechanism of Ser palmitoyltransferase from squash are
      similar to those of the animal, fungal, and bacterial enzyme in most respects.
      The specific activity of the enzyme in squash microsomes ranged from 0.57 to 0.84
      nmol min-1 mg-1 of protein, values 2- to 20-fold higher than those previously
      reported for preparations from animal tissues.

PMID- 12232037
TI  - The Regulation of Pyruvate Dehydrogenase Activity in Pea Leaf Mitochondria (The
      Effect of Respiration and Oxidative Phosphorylation).
AB  - The regulation of the pea (Pisum sativum) leaf mitochondrial pyruvate
      dehydrogenase complex by respiratory rate and oxidative phosphorylation has been
      investigated by measuring the respiratory activity, the redox poise of the
      quinone pool (Q-pool), and mitochondrial pyruvate dehydrogenase (mtPDC) activity
      under various metabolic conditions. It was found that, under state 4 conditions,
      mtPDC activity was unaffected by either the addition of succinate, 2
      oxoglutarate, or glycine or the overall respiratory rate and redox poise of the Q
      pool but was partially inhibited by NADH due to product inhibition. In the
      presence of ADP significant inactivation of PDC, which was sensitive to
      oligomycin, was observed with all substrates, apart from pyruvate, suggesting
      that inactivation was due to ATP formation. Inactivation of PDC by ADP addition
      was observed even in the presence of carboxyatractyloside, an inhibitor of the
      ATP/ADP translocator, suggesting that other mechanisms to facilitate the entry of
      adenylates, in addition to the adenylate carrier, must exist in plant
      mitochondria.

PMID- 12232038
TI  - Nitrate Reductase from the Marine Diatom Skeletonema costatum (Biochemical and
      Immunological Characterization).
AB  - Assimilatory nitrate reductase (NR) was purified from the marine diatom
      Skeletonema costatum (clone Skel) using Cibacron blue-Sepharose affinity
      chromatography. The single-step purification scheme yielded a 103-fold
      purification of specific activity with an overall recovery of 40.8%. Only NADH
      dependent NR activity (form EC 1.6.6.1) was observed in this species. Kinetic
      analysis revealed that this form had apparent Michaelis constants of 3.6 [mu]M
      for NADH and 295 [mu]M for NO3- when purified from cells grown in NO3--enriched
      seawater. The S. costatum NR exhibits a pH optimum of 7.4, a temperature optimum
      of 14[deg]C, and enzyme activity not sensitive to Mg2+ inhibition. The strong
      temperature dependence of NR activity in S. costatum may contribute to the
      seasonal and latitudinal distributions and abundances of this bloom-forming
      species. Chromatographically isolated NR was further purified by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, yielding a single polypeptide with an
      apparent molecular mass of 110 kD. The 110-kD polypeptide was used to generate
      polyclonal antibodies. The antiserum recognized a single 110-kD polypeptide in
      western blots of total proteins from S. costatum, as well as the native enzyme.
      Western blot analysis also revealed an antigenic similarity of NR from two
      additional diatom species, whereas no cross-reactivity was observed with NR from
      other phytoplankton taxa, including prymnesiophytes, dinoflagellate,
      cyanobacterium, and green alga. This result suggests a structural diversity of NR
      in phytoplankton and identifies the potential for development of taxon-specific
      NR antisera for ecological studies.

PMID- 12232040
TI  - The natural center of chromaticity space is not always achromatic: a new look at
      color induction.
AB  - Although current theories of color vision differ in many respects, they all
      assume the existence of a uniquely defined neutral point in chromaticity space.
      It generally is assumed that this point satisfies several criteria
      simultaneously. One of these criteria is that it is perceived as achromatic. A
      further criterion shared by most theories is the structural assumption that lines
      in chromaticity space of constant hue converge on the neutral point. The basic
      assumption that these two criteria coincide is clearly true for isolated spots of
      light presented in darkness, and it usually is taken for granted that this
      coincidence generalizes to more complex visual stimuli. Here, we show that this
      is not the case. Our experiments with infields in chromatic surrounds revealed
      that the point in chromaticity space that appears gray is clearly different from
      the point on which lines of constant hue converge. A plausible interpretation of
      this apparently paradoxical finding in terms of color scission is proposed.

PMID- 12232041
TI  - Linking individuals with ecosystems: experimentally identifying the relevant
      organizational scale for predicting trophic abundances.
AB  - Ecosystems are complex owing to the fact that emergent properties like trophic
      structure and productivity depend on details related to lower-scale interactions
      among individuals. A key challenge is identifying how much individual-level
      detail is needed to predict patterns at the ecosystem level. We tested for the
      effect of individual herbivore body size on trophic interactions and consequent
      abundances of plant and herbivore trophic levels in a New England meadow
      ecosystem. Body size is an important determinant of vulnerability to predation
      and thus should influence the way individuals tradeoff time spent foraging
      against time spent avoiding contact with predators. Such tradeoffs can then
      influence the degree of damage herbivores inflict on their plant resources. We
      experimentally assigned field-caught grasshoppers to three distinct body size
      treatment groups (small, normal, and large) and crossed them with two spider
      predator treatments (spider present and absent) in a fully replicated design. We
      observed size-dependent differences in grasshopper survival and development.
      Moreover, predators caused grasshoppers to inflict greater damage to herbs and
      lesser damage to grasses relative to treatments without predators. However, there
      were no size-dependent differences in net damage level on grasses and herbs in
      either predator or no predator treatments owing to size-dependent compensation in
      grasshopper foraging effort. We thus conclude that in this ecosystem the foraging
      predation risk tradeoff displayed by typical or average-sized herbivore is a
      sufficient amount of individual-level detail needed to explain ecosystem
      patterns.

PMID- 12232042
TI  - A push-pull approach to maximize vaccine efficacy: abrogating suppression with an
      IL-13 inhibitor while augmenting help with granulocyte/macrophage colony
      stimulating factor and CD40L.
AB  - Although a role for CD4(+) helper cells in CD8(+) cytotoxic T lymphocyte (CTL)
      induction by vaccines is widely recognized, much less is known about a
      counterbalancing role of CD4(+) T cells in down-modulating this response, or
      about ways to optimize vaccine responses through abrogation of this negative
      regulatory mechanism. Here, we discovered a synergistic enhancement of vaccine
      mediated CTL induction and protection by the relief of suppression through
      depletion of regulatory CD4(+) cells, including CD4(+) NKT cells, or blockade of
      IL-13 made by these cells, combined with the cytokine granulocyte/macrophage
      colony-stimulating factor and the costimulatory molecule CD40L. Indeed, in the
      absence of helper epitopes, granulocyte/macrophage colony-stimulating factor and
      the helper-mimetic molecule CD40L are not sufficient to replace help to induce
      CTL without abrogation of CD4(+) T cell-mediated suppression, suggesting a role
      for T cell help in overcoming suppression. The increased CTL induction translated
      to striking protection against viral infection by a vaccine by using this
      synergistic combined approach. These results argue for a push-pull approach to
      maximize vaccine efficacy, especially for HIV and cancer.

PMID- 12232043
TI  - p38 MAPK enhances STAT1-dependent transcription independently of Ser-727
      phosphorylation.
AB  - The transcription factor signal transducer and activator of transcription 1
      (STAT1) requires phosphorylation at both Tyr-701 and Ser-727 for full activation.
      IFN-gamma induces phosphorylation of both residues, whereas stress signals like
      UV or lipopolysaccharide stimulate phosphorylation of Ser-727 only. Using
      p38alpha mitogen-activated protein kinase (MAPK)-deficient cells, we show that
      the stress-induced phosphorylation of Ser-727 requires p38alpha MAPK activity,
      whereas IFN-gamma-stimulated Ser-727 phosphorylation occurs independently of the
      p38alpha pathway. Consistently, IFN-gamma stimulated expression of the STAT1
      target gene IRF1 to a similar extent in both wild-type and p38alpha-deficient
      cells. However, stress-induced activation of the p38 MAPK pathway considerably
      enhanced the IFN-gamma-induced expression of both the endogenous IRF1 gene and a
      reporter driven by the IFN-gamma-activated sequence element of the IRF1 promoter.
      This enhancement occurred independently of increased phosphorylation of Ser-727
      by the p38 pathway. Taken together, these results demonstrate an interaction
      between IFN-gamma signaling and the p38 pathway that leads to increased
      transcriptional activation by STAT1 independently of phosphorylation at Ser-727.

PMID- 12232044
TI  - Therapeutic neonatal hepatic gene therapy in mucopolysaccharidosis VII dogs.
AB  - Dogs with mucopolysaccharidosis VII (MPS VII) were injected intravenously at 2-3
      days of age with a retroviral vector (RV) expressing canine beta-glucuronidase
      (cGUSB). Five animals received RV alone, and two dogs received hepatocyte growth
      factor (HGF) before RV in an attempt to increase transduction efficiency.
      Transduced hepatocytes expanded clonally during normal liver growth and secreted
      enzyme with mannose 6-phosphate. Serum GUSB activity was stable for up to 14
      months at normal levels for the RV-treated dogs, and for 17 months at 67-fold
      normal for the HGF/RV-treated dog. GUSB activity in other organs was 1.5-60% of
      normal at 6 months for two RV-treated dogs, which was likely because of uptake of
      enzyme from blood by the mannose 6-phosphate receptor. The body weights of
      untreated MPS VII dogs are 50% of normal at 6 months. MPS VII dogs cannot walk or
      stand after 6 months, and progressively develop eye and heart disease. RV- and
      HGF/RV-treated MPS VII dogs achieved 87% and 84% of normal body weight,
      respectively. Treated animals could run at all times of evaluation for 6-17
      months because of improvements in bone and joint abnormalities, and had little or
      no corneal clouding and no mitral valve thickening. Despite higher GUSB
      expression, the clinical improvements in the HGF/RV-treated dog were similar to
      those in the RV-treated animals. This is the first successful application of gene
      therapy in preventing the clinical manifestations of a lysosomal storage disease
      in a large animal.

PMID- 12232045
TI  - High efficiency genetic modification of hair follicles and growing hair shafts.
AB  - A technique for genetic modification of hair follicles was developed which
      results in efficient alteration of the hair shaft phenotype. High-level in vivo
      transgene expression was maintained in hair follicles such that growing hair
      shafts were phenotypically altered. Mouse anagen skin fragments, maintained in
      histoculture, were genetically modified at high efficiency with adenoviral-GFP.
      The histocultured skin fragments were treated with collagenase which made hair
      follicles accessible to the adenoviral GFP gene, allowing high-efficiency
      transduction. These skin fragments were subsequently grafted on to nude mice
      where GFP was readily visualized in as many as 75% of hair follicles. Most
      follicles produced GFP-fluorescent growing hair shafts. This technique has
      produced efficient genetic modification of the hair shaft.

PMID- 12232046
TI  - Delayed onset of brain edema and mislocalization of aquaporin-4 in dystrophin
      null transgenic mice.
AB  - Cerebral water accumulation was studied during induction of brain edema in
      dystrophin-null transgenic mice (mdx-betageo) and control mice.
      Immunofluorescence and immunoelectron microscopic analyses of dystrophin-null
      brains revealed a dramatic reduction of AQP4 (aquaporin-4) in astroglial end-feet
      surrounding capillaries (blood-brain barrier) and at the glia limitans
      (cerebrospinal fluid-brain interface). The AQP4 protein is mislocalized, because
      immunoblotting showed that the total AQP4 protein abundance was unaltered. Brain
      edema was induced by i.p. injection of distilled water and 8-deamino-arginine
      vasopressin. Changes in cerebral water compartments were assessed by diffusion
      weighted MRI with determination of the apparent diffusion coefficient (ADC). In
      dystrophin-null mice and control mice, ADC gradually decreased by 5-6% from
      baseline levels during the first 35 min, indicating the initial phase of
      intracellular water accumulation is similar in the two groups. At this point, the
      control mice sustained an abrupt, rapid decline in ADC to 58% +/- 2.2% of the
      baseline at 52.5 min, and all of the animals were dead by 56 min. After a
      consistent delay, the dystrophin-null mice sustained a similar decline in ADC to
      55% +/- 3.4% at 66.5 min, when all of the mice were dead. These results
      demonstrate that dystrophin is necessary for polarized distribution of AQP4
      protein in brain where facilitated movements of water occur across the blood
      brain barrier and cerebrospinal fluid-brain interface. Moreover, these results
      predict that interference with the subcellular localization of AQP4 may have
      therapeutic potential for delaying the onset of impending brain edema.

PMID- 12232047
TI  - Binding of the Escherichia coli response regulator CheY to its target measured in
      vivo by fluorescence resonance energy transfer.
AB  - In Escherichia coli chemotaxis, signaling depends on modulation of the level of
      phosphorylation of CheY, a small protein that couples receptors and flagellar
      motors. Working in vivo, we used fluorescence resonance energy transfer (FRET) to
      measure the interaction of CheY approximately P with its target, FliM. Binding of
      CheY approximately P to FliM was found to be much less cooperative than motor
      switching; however, under the conditions of our experiment, most of the FliM
      appeared to be in the cytoplasm. We studied signal processing times in the
      chemotaxis pathway by measuring the changes in CheY approximately P binding to
      FliM on flash release of caged chemoeffectors. Following sudden addition of
      attractant, the amount of CheY approximately P bound to FliM decayed
      exponentially with a rate constant of about 2 s(-1). Following sudden addition of
      repellent, FliM occupancy increased with a rate constant of about 20 s(-1). Using
      these data, we were able to construct a simple model for the chemotactic pathway
      and to estimate values of rate constants for several key reactions.

PMID- 12232048
TI  - Molecular cloning and heterologous expression of the C-13 phenylpropanoid side
      chain-CoA acyltransferase that functions in Taxol biosynthesis.
AB  - The structural pharmacophore of Taxol, responsible for binding the N terminus of
      the beta-subunit of tubulin to arrest cell proliferation, comprises, in part, the
      13-O-(N-benzoyl-3-phenylisoserinoyl) side chain. To identify the side chain
      transferase of Taxol biosynthesis, a set of transacylases obtained from an
      enriched cDNA library (constructed from mRNA isolated from Taxus cuspidata cells
      induced with methyl jasmonate for Taxol production) was screened. A cDNA clone
      (designated TAX7) encoding a taxoid C-13 O-phenylpropanoyltransferase was
      isolated which yielded a recombinant enzyme that catalyzes the selective 13-O
      acylation of baccatin III with beta-phenylalanoyl CoA as the acyl donor to form N
      debenzoyl-2'-deoxytaxol. This enzymatic product was converted to 2'-deoxytaxol by
      chemical N-benzoylation, and the identity of this derivative was confirmed by
      spectrometric analyses. The full-length cDNA has an ORF of 1,335 bases and
      encodes a 445-aa protein with a calculated molecular weight of 50,546. Evaluation
      of kinetic parameters revealed K(m) values of 2.4 +/- 0.5 microM and 4.9 +/- 0.3
      microM for baccatin III and beta-phenylalanoyl-CoA, respectively. The pH optimum
      for the recombinant O-(3-amino-3-phenylpropanoyl)transferase is at 6.8.
      Identification of this clone completes acquisition of the five
      aroyl/acyltransferases involved in the biosynthesis of Taxol. Application of
      these transacylase genes in suitable host cells can improve the production yields
      of Taxol and could enable the preparation of second-generation Taxol analogs
      possessing greater bioactivity and improved water solubility.

PMID- 12232049
TI  - The Neandertal type site revisited: interdisciplinary investigations of skeletal
      remains from the Neander Valley, Germany.
AB  - The 1856 discovery of the Neandertal type specimen (Neandertal 1) in western
      Germany marked the beginning of human paleontology and initiated the longest
      standing debate in the discipline: the role of Neandertals in human evolutionary
      history. We report excavations of cave sediments that were removed from the
      Feldhofer caves in 1856. These deposits have yielded over 60 human skeletal
      fragments, along with a large series of Paleolithic artifacts and faunal
      material. Our analysis of this material represents the first interdisciplinary
      analysis of Neandertal remains incorporating genetic, direct dating, and
      morphological dimensions simultaneously. Three of these skeletal fragments fit
      directly on Neandertal 1, whereas several others have distinctively Neandertal
      features. At least three individuals are represented in the skeletal sample.
      Radiocarbon dates for Neandertal 1, from which a mtDNA sequence was determined in
      1997, and a second individual indicate an age of approximately 40,000 yr for
      both. mtDNA analysis on the same second individual yields a sequence that
      clusters with other published Neandertal sequences.

PMID- 12232050
TI  - Divergent effects of new cyclooxygenase inhibitors on gastric ulcer healing:
      Shifting the angiogenic balance.
AB  - Delayed gastric ulcer healing is a well recognized problem associated with the
      use of cyclooxygenase (COX) inhibitors. In contrast, NO-releasing COX inhibitors
      do not interfere with ulcer healing. These divergent effects may in part be due
      to differences in their effects on platelets, which are known to influence ulcer
      healing. Therefore, we compared the effects of a nonselective COX inhibitor
      (flurbiprofen), a nitric oxide-releasing COX inhibitor (HCT-1026), and a
      selective COX-2 inhibitor (celecoxib) on gastric ulcer healing, angiogenesis, and
      platelet/serum levels of vascular endothelial growth factor (VEGF) and
      endostatin. Gastric ulcers were induced in rats by serosal application of acetic
      acid. Daily treatment with the test drugs was started 3 days later and continued
      for 1 week. Celecoxib and flurbiprofen impaired angiogenesis and delayed ulcer
      healing, as well as increasing serum endostatin levels relative to those of VEGF.
      HCT-1026 did not delay ulcer healing nor impair angiogenesis, and also did not
      change the ratio of serum endostatin to VEGF. Incubation of human umbilical vein
      endothelial cells with serum from celecoxib- or flurbiprofen-treated rats
      resulted in suppressed proliferation and increased apoptosis, effects that were
      reversed by an antiendostatin antibody. These results demonstrate a previously
      unrecognized mechanism through which nonsteroidal antiinflammatory drugs can
      delay ulcer healing, namely, through altering the balance of anti- and
      proangiogenic factors in the serum. The absence of a delaying effect of HCT-1026
      on ulcer healing may be related to the maintenance of a more favorable balance in
      serum levels of pro- and antiangiogenic growth factors.

PMID- 12232051
TI  - Circuits and programmable self-assembling DNA structures.
AB  - Self-assembly is beginning to be seen as a practical vehicle for computation. We
      investigate how basic ideas on tiling can be applied to the assembly and
      evaluation of circuits. We suggest that these procedures can be realized on the
      molecular scale through the medium of self-assembled DNA tiles. One layer of self
      assembled DNA tiles will be used as the program or circuit that leads to the
      computation of a particular Boolean expression. This layer templates the assembly
      of tiles, and their associations then lead to the actual evaluation involving the
      input data. We describe DNA motifs that can be used for this purpose; we show how
      the template layer can be programmed, in much the way that a general-purpose
      computer can run programs for a variety of applications. The molecular system
      that we describe is fundamentally a pair of two-dimensional layers, but it seems
      possible to extend this system to multiple layers.

PMID- 12232055
TI  - Microtubule Components of the Plant Cell Cytoskeleton.

PMID- 12232052
TI  - Sequence-specific DNA binding by the vnd/NK-2 homeodomain of Drosophila.
AB  - The ventral nervous system defective (vnd)/NK-2 homeodomain and some flanking
      amino acid residues were expressed in Escherichia coli, purified to homogeneity,
      and the protein was covalently coupled to Sepharose. Oligodeoxynucleotides that
      contained 16-bp random sequences were purified by vnd/NK-2 affinity column
      chromatography, cloned, and sequenced. The consensus nucleotide sequence of the
      vnd/NK-2 homeodomain binding site was shown to be T(T/C)AAGTG(G/C). The apparent
      equilibrium dissociation constant (K(D)) of the vnd/NK-2 homeodomain for the
      consensus sequence is 1.9 x 10(-10) M. In addition, results of competition
      between oligodeoxynucleotides for binding to the vnd/NK-2 homeodomain and
      determination of the apparent K(D) values of oligodeoxynucleotides that differ
      from the consensus sequence by only a single base pair demonstrate that the four
      central nucleotides, AAGT, in this sequence play a major role in determining the
      affinity of binding.

PMID- 12232053
TI  - Mdm-2 and ubiquitin-independent p53 proteasomal degradation regulated by NQO1.
AB  - The tumor suppressor p53 is a labile protein whose level is known to be regulated
      by the Mdm-2-ubiquitin-proteasome degradation pathway. We have found another
      pathway for p53 proteasomal degradation regulated by NAD(P)H quinone
      oxidoreductase 1 (NQO1). Inhibition of NQO1 activity by dicoumarol induces p53
      and p73 proteasomal degradation. A mutant p53 (p53([22,23])), which is resistant
      to Mdm-2-mediated degradation, was susceptible to dicoumarol-induced degradation.
      This finding indicates that the NQO1-regulated proteasomal p53 degradation is Mdm
      2-independent. The tumor suppressor p14(ARF) and the viral oncogenes SV40 LT and
      adenovirus E1A that are known to stabilize p53 inhibited dicoumarol-induced p53
      degradation. Unlike Mdm-2-mediated degradation, the NQO1-regulated p53
      degradation pathway was not associated with accumulation of ubiquitin-conjugated
      p53. In vitro studies indicate that dicoumarol-induced p53 degradation was
      ubiquitin-independent and ATP-dependent. Inhibition of NQO1 activity in cells
      with a temperature-sensitive E1 ubiquitin-activating enzyme induced p53
      degradation and inhibited apoptosis at the restrictive temperature without
      ubiquitination. Mdm-2 failed to induce p53 degradation under these conditions.
      Our results establish a Mdm-2- and ubiquitin-independent mechanism for
      proteasomal degradation of p53 that is regulated by NQO1. The lack of NQO1
      activity that stabilizes a tumor suppressor such as p53 can explain why humans
      carrying a polymorphic inactive NQO1 are more susceptible to tumor development.

PMID- 12232056
TI  - Monitoring Phloem Unloading and Post-Phloem Transport by Microperfusion of
      Attached Wheat Grains.
AB  - Phloem unloading and post-phloem transport in developing wheat (Triticum aestivum
      L.) grains were investigated by perfusing the endosperm cavities of attached
      grains. Relative unloading ratio (RUR) and the rate of sucrose release into the
      endosperm cavity (SRR) were calculated, respectively, from 14C import and from
      sucrose washout from the cavity. RUR and SRR continued at or near in vivo rates
      over a wide range of cavity sap osmolality (90 to approximately 500 milliosmolal)
      and sucrose concentration (14-430 mM) and for long times (29 h). These are much
      greater ranges than have been observed for the endosperm cavity in vivo (230-300
      milliosmolal, and 40-120 mM, respectively), indicating that neither the cavity
      sap osmolality nor sucrose concentration are controlling factors for the rate of
      assimilate import into the cavity. The maintenance of in vivo transport rates
      over a wide range of conditions strongly implicates the role of transport
      processes within the maternal tissues of the wheat grain, rather than activities
      of the embryo or endosperm, in determining the rate of assimilate import into the
      grain. RUR was decreased by high concentrations of sucrose and sorbitol, but not
      of mannitol. By plasmolyzing some chalazal cells, sorbitol appeared to block
      symplastic transport across the crease tissues, but neither sucrose nor mannitol
      caused plasmolysis in maternal tissues of attached grains. The inhibition of RUR
      by KCN and carbonyl cyanide m-chlorophenyl (CCCP) and the continued import of
      sucrose into grains against its concentration gradient suggest that solute
      movement into the endosperm cavity might occur by active membrane transport.
      However, the evidence is weak, since KCN and CCCP appeared to act primarily on
      some aspect of symplastic (i.e. nonmembrane) transport. Also, sucrose could move
      from the endosperm cavity into the maternal tissues (i.e. opposite to the normal
      direction of sucrose movement), suggesting that transmembrane movement in the
      nucellus may be a reversible process. Pressure-driven flow into the grain could
      account for movement against a concentration gradient.

PMID- 12232057
TI  - The Use of Fluorescent Tracers to Characterize the Post-Phloem Transport Pathway
      in Maternal Tissues of Developing Wheat Grains.
AB  - Various polar fluorescent tracers were used to characterize the pathways for
      apoplastic and symplastic transport in the "crease tissues" (i.e. the vascular
      strand, chalaza, nucellus, and adjacent pericarp) of developing wheat (Triticum
      aestivum L.) grains. With mostly minor exceptions, the results strongly support
      existing views of phloem unloading and post-phloem transport pathways in the
      crease. Apoplastic movement of Lucifer yellow CH (LYCH) from the endosperm cavity
      into the crease was virtually blocked in the chalazal cell walls before reaching
      the vascular tissue. However, LYCH could move slowly along the cell wall pathway
      from the chalaza into the vascular parenchyma. Slow uptake of LYCH into nucellar
      cell cytoplasm was observed, but no subsequent symplastic movement occurred.
      Carboxyfluorescein (CF) imported into attached grains moved symplastically from
      the phloem across the chalaza and into the nucellus, but was not released from
      the nucellus. In addition, CF moved in the opposite direction (nucellus to
      vascular parenchyma) in attached grains. Thus, the post-phloem symplastic pathway
      can accommodate bidirectional transport even when there is an intense net
      assimilate flux in one direction. When fresh sections of the crease were placed
      in fluorochrome solutions (e.g. LYCH or pyrene trisulfonate), dye was rapidly
      absorbed into intact cells, apparently via unsealed plasmodesmata. Uptake was not
      visibly reduced by cold or by respiratory inhibitors, but was greatly reduced by
      plasmolysis. Once absorbed, the dye moved intercellularly via the symplast. Based
      on this finding, a size-graded series of fluorescein-labeled dextrans was used to
      estimate the size-exclusion limits (SEL) for the post-phloem symplastic pathway.
      In most, and perhaps all, cells of the crease tissues except for the pericarp,
      the molecular diameter for the SEL was about 6.2 nm. The SEL in much of the
      vascular parenchyma may be smaller, but it is still at least 3.6 nm. Channel
      diameters would likely be about 1 nm larger, or about 4.5 to 7.0 nm in the
      vascular parenchyma and 7.0 nm elsewhere. These dimensions are substantially
      larger than those for "conventional" symplastic connections (about 3 nm), and
      would have a greater than proportionate effect on the per channel diffusive and
      hydraulic conductivities of the pathway. Thus, relatively small and probably
      ultrastructurally undetectable adjustments in plasmodesmatal structure may be
      sufficient to account for assimilate flux through the crease symplast.

PMID- 12232058
TI  - Tissue Level Compartmentation of (R)-Amygdalin and Amygdalin Hydrolase Prevents
      Large-Scale Cyanogenesis in Undamaged Prunus Seeds.
AB  - Plum (Prunus domestica) seeds, which contain the cyanogenic diglucoside (R)
      amygdalin and lesser amounts of the corresponding monoglucoside (R)-prunasin,
      release the respiratory toxin HCN upon tissue disruption. Amygdalin hydrolase
      (AH) and prunasin hydrolase (PH), two specific [beta]-glucosidases responsible
      for hydrolysis of these glucosides, were purified to near homogeneity by
      concanavalin A-Sepharose 4B and carboxymethyl-cellulose chromatography. Both
      proteins appear as polypeptides with molecular masses of 60 kD upon sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, but they exhibit different
      isoelectric points (PH, 5.6-6.0; AH, 7.8-8.2). AH and PH were localized within
      mature plum seeds by tissue printing, histochemistry, and silver-enhanced
      immunogold labeling. As was previously shown in black cherry (Prunus serotina)
      seeds (E.Swain, C.P. Li, J.E. Poulton [1992] Plant Physiol 100: 291-300), AH and
      PH are restricted to protein bodies of specific procambial cells and are absent
      from the cotyledonary parenchyma, bundle sheath, and endosperm cells. In
      contrast, the cyanogenic glycosides in both plum and black cherry seeds, which
      were detected by tissue printing, occur solely in the cotyledonary parenchyma and
      are absent from the procambium and endosperm. It is concluded that tissue level
      compartmentation prevents large-scale cyanoglycoside hydrolysis in intact Prunus
      seeds.

PMID- 12232059
TI  - Generation of Large Numbers of Independently Transformed Fertile Barley Plants.
AB  - A rapid, efficient, and reproducible system to generate large numbers of
      independently transformed, self-fertile, transgenic barley (Hordeum vulgare L.)
      plants is described. Immature zygotic embryos, young callus, and microspore
      derived embryos were bombarded with a plasmid containing bar and uidA either
      alone or in combination with another plasmid containing a barley yellow dwarf
      virus coat protein (BYDVcp) gene. A total of 91 independent bialaphos-resistant
      callus lines expressed functional phosphinothricin acetyltransferase, the product
      of bar. Integration of bar was confirmed by DNA hybridization in the 67 lines
      analyzed. Co-transformation frequencies of 84 and 85% were determined for the two
      linked genes (bar and uidA) and for two unlinked genes (bar and the BYDVcp gene),
      respectively. More than 500 green, fertile, transgenic plants were regenerated
      from 36 transformed callus lines on bialaphos-containing medium; albino plants
      only were regenerated from 41 lines. T0 plants in 25 lines (three plants per
      line) were analyzed by DNA hybridization, and all contained bar. Most contained
      the same integration patterns for the introduced genes (bar, uidA, and the BYDVcp
      gene) as their parental callus lines. Transmission of the genes to T1 progeny was
      confirmed in the five families analyzed by DNA hybridization. A germination test
      of immature T1 embryos on bialaphos-containing medium was useful for selecting
      individuals that were actively expressing bar, although this was not a good
      indicator of the presence or absence of bar. Expression of bar in some progeny
      plants was indicated by resistance to the herbicide Basta. The T1 plants were in
      soil approximately 7 months after bombardment of the immature embryo.

PMID- 12232060
TI  - Purification of the Major Soybean Leaf Acid Phosphatase That Is Increased by Seed
      Pod Removal.
AB  - Fruit removal for 5 weeks after flowering increased acid phosphatase activity 10
      fold in soybean (Glycine max L. Merr. Var Hobbit) leaves compared with normal
      seed-pod-bearing plants. The major acid phosphatase activity in leaves was
      purified over 2700-fold, yielding a single polypeptide of 51 kD with a specific
      activity of 1353 units/mg protein using p-nitrophenylphosphate as the substrate.
      Isoelectric focusing demonstrated that the purified protein co-migrated with a
      majority of the activity that increased in leaves following seed-pod removal.
      Immunoblot analysis demonstrated that at least part of the increased activity was
      due to an increased abundance of the phosphatase protein. In situ enzyme activity
      staining localized most of the total phosphatase activity to vascular tissues,
      the leaf paraveinal mesophyll cell layer, and the lower epidermis. This
      distribution and the response to seed-pod removal paralleled previous results for
      soybean vegetative storage protein (VSP) [alpha] and [beta]. However, in a native
      polyacrylamide gel the VSP detected by immunological staining of
      electrophoretically transferred protein did not migrate with the majority of the
      phosphatase activity. Fractionation of crude leaf protein on concanavalin A
      Sepharose yielded a fraction containing 97% of the total VSP but only 0.1% of the
      total acid phosphatase activity.

PMID- 12232061
TI  - [beta]-Aminobutyric Acid Induces the Accumulation of Pathogenesis-Related
      Proteins in Tomato (Lycopersicon esculentum L.) Plants and Resistance to Late
      Blight Infection Caused by Phytophthora infestans.
AB  - Tomato (Lycopersicon esculentum L.) plants were sprayed with aqueous solutions of
      isomers of aminobutyric acid and were either analyzed for the accumulation of
      pathogenesis-related (PR) proteins or challenged with the late blight fungal
      agent Phytophthora infestans. The [beta] isomer of aminobutyric acid induced the
      accumulation of high levels of three proteins: P14a, [beta]-1,3 glucanase, and
      chitinase. These proteins either did not accumulate or accumulated to a much
      lower level in [alpha]- or [gamma]-aminobutyric acid-treated plants. Plants
      pretreated with [alpha]-, [beta]-, and [gamma]-aminobutyric acid were protected
      up to 11 d to an extent of 35, 92, and 6%, respectively, against a challenge
      infection with P. infestans. Protection by [beta]-aminobutyric acid was afforded
      against the blight even when the chemical was applied 1 d postinoculation.
      Examination of ethylene evolution showed that [alpha]-aminobutyric acid induced
      the production of 3-fold higher levels of ethylene compared with [beta]
      aminobutyric acid, whereas [gamma]-aminobutyric acid induced no ethylene
      production. In addition, silver thiosulfate, a potent inhibitor of ethylene
      action, did not abolish the resistance induced by [beta]-aminobutyric acid. The
      results are consistent with the possibility that [beta]-aminobutyric acid
      protects tomato foliage against the late blight disease by a mechanism that is
      not mediated by ethylene and that PR proteins can be involved in induced
      resistance.

PMID- 12232062
TI  - Biochemical Plant Responses to Ozone (IV. Cross-Induction of Defensive Pathways
      in Parsley (Petroselinum crispum L.) Plants).
AB  - Parsley (Petroselinum crispum L.) is known to respond to ultraviolet irradiation
      by the synthesis of flavone glycosides, whereas fungal or elicitor stress leads
      to the synthesis of furanocoumarin phytoalexins. We tested how these defensive
      pathways are affected by a single ozone treatment (200 nL L-1; 10 h). Assays were
      performed at the levels of transcripts, for enzyme activities, and for secondary
      products. The most rapid transcript accumulation was maximal at 3 h, whereas
      flavone glycosides and furanocoumarins were maximally induced at 12 and 24 h,
      respectively, after the start of ozone treatment. Ozone acted as a cross-inducer
      because the two distinct pathways were simultaneously induced. These results are
      consistent with the previously observed ozone induction of fungal and viral
      defense reactions in tobacco, spruce, and pine.

PMID- 12232063
TI  - Purification and Characterization of Cinnamyl Alcohol Dehydrogenase Isoforms from
      the Periderm of Eucalyptus gunnii Hook.
AB  - Cinnamyl alcohol dehydrogenase (CAD, EC 1.1.1.195) isoforms were purified from
      the periderm (containing both suberized and lignified cell layers) of Eucalyptus
      gunnii Hook stems. Two isoforms (CAD 1P and CAD 2P) were initially characterized,
      and the major form, CAD 2P, was resolved into three further isoforms by ion
      exchange chromatography. Crude extracts contained two aliphatic alcohol
      dehydrogenases (ADH) and one aromatic ADH, which was later resolved into two
      further isoforms. Aliphatic ADHs did not use hydroxycinnamyl alcohols as
      substrates, whereas both aromatic ADH isoforms used coniferyl and sinapyl alcohol
      as substrates but with a much lower specific activity when compared with benzyl
      alcohol. The minor form, CAD 1P, was a monomer with a molecular weight of 34,000
      that did not co-elute with either aromatic or aliphatic ADH activity. Sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blot
      analysis demonstrated that this protein was very similar to another CAD isoform
      purified from Eucalyptus xylem tissue. CAD 2P had a native molecular weight of
      approximately 84,000 and was a dimer consisting of two heterogenous subunits
      (with molecular weights of 42,000 and 44,000). These subunits were differentially
      combined to give the heterodimer and two homodimers. SDS-PAGE, western blots, and
      nondenaturing PAGE indicated that the CAD 2P heterodimer was very similar to the
      main CAD isoform previously purified in our laboratory from differentiating xylem
      tissue of E. gunnii (D. Goffner, I. Joffroy, J. Grima-Pettenati, C. Halpin, M.E.
      Knight, W. Schuch, A.M. Boudet [1992] Planta 188: 48-53). Kinetic data indicated
      that the different CAD 2P isoforms may be implicated in the preferential
      production of different monolignols used in the synthesis of lignin and/or
      suberin.

PMID- 12232064
TI  - Essentiality of Boron for Symbiotic Dinitrogen Fixation in Pea (Pisum sativum)
      Rhizobium Nodules.
AB  - The effect of boron deficiency on symbiotic nitrogen fixation in pea (Pisum
      sativum) was examined. The absence of boron in the culture medium resulted in a
      decrease of the number of nodules and an alteration of nodule development leading
      to an inhibition of nitrogenase activity. Examination of boron-deficient nodules
      showed dramatic changes in cell walls and in both peribacteroid and infection
      thread membranes, suggesting a role for boron in the stability of these
      structures. These results indicate that boron is a requirement for normal nodule
      development and functionality.

PMID- 12232065
TI  - Production and Characterization of Monoclonal Antibodies against Aspartate
      Aminotransferase-P1 from Lupin Root Nodules.
AB  - Six hybridoma clones were obtained that secreted monoclonal antibodies against
      the aspartate aminotransferase-P1 (AAT-P1) isoenzyme from root nodules of Lupinus
      angustifolius [L.] cv Uniharvest. This enzyme is found constitutively in the
      plant cytosol fraction. The monoclonal antibodies produced were all of the
      immunoglobulin G1 class, recognized two distinct epitopes on the protein, and
      represented the major paratopes found in the immunoglobulin fraction of sera
      taken from mice and rabbits immunized with the pure AAT-P1 protein. One of these
      epitopes was unique to lupin nodule AAT-P1. The other epitope was shown to be
      present on enzyme from lupin bean, white clover and tobacco leaves, lupin roots
      and nodules, and potato tubers. Both epitopes were recognized by the appropriate
      monoclonal antibodies in both their native and denatured forms. None of the
      monoclonal antibodies produced reacted with Rhizobium lupini NZP2257, Escherichia
      coli extracts, or with the inducible aspartate aminotransferase-P2 (AAT-P2)
      isoform also found in root nodules. A sandwich enzyme-linked immunosorbent assay
      utilizing two monoclonal antibodies recognizing the two distinct epitopes was
      developed and was capable of quantitating AAT-P1 in plant extracts. The limit of
      detection of AAT-P1 was less than 15 pg/mL and AAT-P1 protein could be quantified
      in the range 80 to 1000 pg/mL. Using this assay, AAT-P1 protein was shown to
      remain relatively constant during nodule development. Use of an AAT-P2-specific
      monoclonal antibody that inhibits the enzyme activity of this isoform enabled the
      direct determination of AAT-P1 enzyme activity in nodule extracts. Using these
      assays, specific activities of the individual isoforms were calculated; that of
      the AAT-P1 isoform was shown to be 7.5-fold higher than that of the AAT-P2
      isoform.

PMID- 12232066
TI  - The Effect of Xyloglucans on the Degradation of Cell-Wall-Embedded Cellulose by
      the Combined Action of Cellobiohydrolase and Endoglucanases from Trichoderma
      viride.
AB  - Two endoglucanases of Trichoderma viride, endoI and endoIV, were assayed for
      their activity toward alkali-extracted apple xyloglucans. EndoIV was shown to
      have a 60-fold higher activity toward xyloglucan than endoI, whereas
      carboxymethyl cellulose and crystalline cellulose were better substrates for the
      latter. The enzymic degradation of cellulose embedded in the complex cell-wall
      matrix of apple fruit tissue has been studied using cellobiohydrolase (CBH) and
      these two different endoglucanases. A high-performance liquid chromatographic
      method (Aminex HPX-22H) was used to monitor the release of cellobiose and
      oligomeric xyloglucan fragments. Synergistic action between CBH and
      endoglucanases on cell-wall-embedded cellulose was, with respect to their optimal
      ratio, slightly different from that reported for crystalline cellulose. The
      combination of endoIV and CBH solubilized twice as much cellobiose compared to a
      combination of endoI and CBH. Apparently, the concomitant removal of the
      xyloglucan coating from cellulose microfibrils by endoIV is essential for an
      efficient degradation of cellulose in a complex matrix. Cellulose degradation
      slightly enhanced the solubilization of xyloglucans. These results indicate
      optimal degradation of cell-wall-embedded cellulose by a three-enzyme system
      consisting of an endoglucanase with high affinity toward cellulose (endoI), a
      xyloglucanase (endoIV), and CBH.

PMID- 12232067
TI  - Expression of Erwinia uredovora Phytoene Desaturase in Synechococcus PCC7942
      Leading to Resistance against a Bleaching Herbicide.
AB  - The gene coding for phytoene desaturase of the bacterium Erwinia uredovora (crtI)
      was inserted into the chromosome of the cyanobacterium Synechococcus PCC7942
      strain R2-PIM8. For expression of crtI in the heterologous host, two constructs
      with different promoters were introduced into Synechococcus. In the first, crtI
      was fused to the 5[prime] region of the psbA gene of the xanthophycean microalga
      Bumilleriopsis filiformis. The second construct carried crtI inserted downstream
      of the neomycin phosphotransferase II gene (nptII) from the transposon Tn5.
      Expression of crtI under the control of the respective promoter was shown by
      immunodetection of the gene product. The functionality of the heterologously
      expressed phytoene desaturase CRTI in the transformants was demonstrated by
      enzymic assays. The transformants acquired very strong resistance toward the
      bleaching herbicide norflurazon.

PMID- 12232068
TI  - Involvement of Phenolic Esters in Cell Aggregation of Suspension-Cultured Rice
      Cells.
AB  - Fluorescence microscopy of rice (Oryza sativa L.) callus sections showed that all
      of the walls fluoresced blue in water (pH 5.8) and green in ammonia (pH 10.0),
      both characteristics of feruloyl esters. Such fluorescence in the walls of cells
      cultured in Gamborg's B5 medium was much stronger than that in amino acid (AA)
      medium. Laser scanning microscopy showed that the level of fluorescence was
      higher in the intercellular layer, especially at corner junctions between cells,
      suggesting that ferulic acid ester derivatives are located in the middle lamella
      as well as in the wall. Extracellular polysaccharides appearing during
      cultivation in AA medium were more highly feruloylated than those in B5 medium
      during cultivation. Both the levels of ferulic and diferulic acid and the
      relative proportion of diferulic acid in the walls of cells increased on transfer
      of the cells cultured in AA medium to B5 medium. The walls of cells cultured in
      B5 medium maintained constant levels and proportions of the phenolic acids.
      Removal of phenolic acids from wall preparations by carboxylesterase facilitated
      the solubilization of noncellulosic polysaccharides. Treatment of the cell
      aggregates grown in AA medium with an enzyme that hydrolyzes feruloyl esters
      decreased the size of the aggregates to between 20 and 500 [mu]m, compared with
      an original size between 200 and 1000 [mu]m. These findings suggest that feruloyl
      and diferuloyl esters between polysaccharides are involved in the aggregation of
      cultured rice cells.

PMID- 12232069
TI  - Aminomethylenediphosphonate: A Potent Type-Specific Inhibitor of Both Plant and
      Phototrophic Bacterial H+-Pyrophosphatases.
AB  - The suitability of different pyrophosphate (PPi) analogs as inhibitors of the
      vacuolar H+-translocating inorganic pyrophosphatase (V-PPase; EC 3.6.1.1) of
      tonoplast vesicles isolated from etiolated hypocotyls of Vigna radiata was
      investigated. Five 1,1-diphosphonates and imidodiphosphate were tested for their
      effects on substrate hydrolysis by the V-PPase at a substrate concentration
      corresponding to the Km of the enzyme. The order of inhibitory potency (apparent
      inhibition constants, Kiapp values, [mu]M, in parentheses) of the compounds
      examined was aminomethylenediphosphonate (1.8) > hydroxymethylenediphosphonate
      (5.7) [almost equal to] ethane-1-hydroxy-1,1-diphosphonate (6.5) >
      imidodiphosphate (12) > methylenediphosphonate (68) >>
      dichloromethylenediphosphonate (>500). The specificity of three of these
      compounds, aminomethylenediphosphonate, imidodiphosphate, and
      methylenediphosphonate, was determined by comparing their effects on the V-PPase
      and vacuolar H+-ATPase from Vigna, plasma membrane H+-ATPase from Beta vulgaris,
      H+-PPi synthase of chromatophores prepared from Rhodospirillum rubrum, soluble
      PPase from Saccharomyces cerevisiae, alkaline phosphatase from bovine intestinal
      mucosa, and nonspecific monophosphoesterase from Vigna at a PPi concentration
      equivalent to 10 times the Km of the V-PPase. Although all three PPi analogs
      inhibited the plant V-PPase and bacterial H+-PPi synthase with qualitatively
      similar kinetics, whether substrate hydrolysis or PPi-dependent H+-translocation
      was measured, neither the vacuolar H+-ATPase nor plasma membrane H+-ATPase nor
      any of the non-V-PPase-related PPi hydrolases were markedly inhibited under these
      conditions. It is concluded that 1, 1-diphosphonates, in general, and
      aminomethylenediphosphonate, in particular, are potent type-specific inhibitors
      of the V-PPase and its putative bacterial homolog, the H+-PPi synthase of
      Rhodospirillum.

PMID- 12232070
TI  - Adaptations of Photosynthetic Electron Transport, Carbon Assimilation, and Carbon
      Partitioning in Transgenic Nicotiana plumbaginifolia Plants to Changes in Nitrate
      Reductase Activity.
AB  - Transgenic Nicotiana plumbaginifolia plants that express either a 5-fold increase
      or a 20-fold decrease in nitrate reductase (NR) activity were used to study the
      relationships between carbon and nitrogen metabolism in leaves. Under saturating
      irradiance the maximum rate of photosynthesis, per unit surface area, was
      decreased in the low NR expressors but was relatively unchanged in the high NR
      expressors compared with the wild-type controls. However, when photosynthesis was
      expressed on a chlorophyll (Chl) basis the low NR plants had comparable or even
      higher values than the wild-type plants. Surprisingly, the high NR expressors
      showed very similar rates of photosynthesis and respiration to the wild-type
      plants and contained identical amounts of leaf Chl, carbohydrate, and protein.
      These plants were provided with a saturating supply of nitrate plus a basal level
      of ammonium during all phases of growth. Under these conditions overexpression of
      NR had little impact on leaf metabolism and did not stimulate growth or biomass
      production. Large differences in photochemical quenching and nonphotochemical
      quenching components of Chl a fluorescence, as well as the ratio of variable to
      maximum fluorescence, (FV/FM), were apparent in the low NR expressors in
      comparison with the wild-type controls. Light intensity-dependent increases in
      nonphotochemical quenching and decreases in FV/FM were greatest in the low NR
      expressors, whereas photochemical quenching decreased uniformly with increasing
      irradiance in all plant types. Nonphotochemical quenching was increased at all
      except the lowest irradiances in the low NR expressors, allowing photosystem II
      to remain oxidized on its acceptor side. The relative contributions of
      photochemical and nonphotochemical quenching of Chl a fluorescence with changing
      irradiance were virtually identical in the high NR expressors and the wild-type
      controls. Zeaxanthin was present in all leaves at high irradiances; however, at
      high irradiance leaves from the low NR expressors contained considerably more
      zeaxanthin and less violaxanthin than wild-type controls or high NR expressors.
      The leaves of the low NR expressors contained less Chl, protein, and amino acids
      than controls but retained more carbohydrate (starch and sucrose) than the wild
      type or high NR expressors. Sucrose phosphate synthase activities were remarkably
      similar in all plant types regardless of the NR activity. In contrast
      phosphoenolpyruvate carboxylase activities were increased on a Chl or protein
      basis in the low NR expressors compared with the wild-type controls or high NR
      expressors. We conclude that large decreases in NR have profound repercussions
      for photosynthesis and carbon partitioning within the leaf but that increases in
      NR have negligible effects.

PMID- 12232071
TI  - Novel Methods of Measuring Hydraulic Conductivity of Tree Root Systems and
      Interpretation Using AMAIZED (A Maize-Root Dynamic Model for Water and Solute
      Transport).
AB  - Steady-state and dynamic methods were used to measure the conductivity to water
      flow in large woody root systems. The methods were destructive in that the root
      must be excised from the shoot but do not require removal of the root from the
      soil. The methods involve pushing water from the excised base of the root to the
      apex, causing flow in a direction opposite to that during normal transpiration.
      Sample data are given for two tropical (Cecropia obtusifolia and Lacistema
      aggregatum) and two temperate species (Acer saccharum and Juglans regia cv Lara).
      A hysteresis was observed in the relationship between applied pressure and
      resulting flow during dynamic measurements. A mathematical model (AMAIZED) was
      derived for the dynamics of solute and water flow in roots. The model was used to
      interpret results obtained from steady-state and dynamic measurements. AMAIZED is
      mathematically identical with the equations that describe Munch pressure flow of
      solute and water in the phloem of leaves. Results are discussed in terms of the
      predictions of AMAIZED, and suggestions for the improvement of methods are made.

PMID- 12232072
TI  - A Genetic Analysis of Chloroplast Division and Expansion in Arabidopsis thaliana.
AB  - A nuclear recessive mutant of Arabidopsis thaliana, arc5, has been isolated in
      which there is no significant increase in chloroplast number during leaf
      mesophyll cell expansion and in which there are only 13 chloroplasts per
      mesophyll cell compared with 121 in wild-type cells. Mature arc5 chloroplasts in
      fully expanded mesophyll cells are 6-fold larger than in wild-type cells. A large
      proportion of arc5 chloroplasts also show some degree of central constriction,
      suggesting that the mutation has prevented the completion of the chloroplast
      division process. To examine the interaction of arc loci, a double mutant was
      constructed between arc1, a mutant possessing many small chloroplasts, and arc5.
      A second double mutant was also constructed between arc3, a previously discovered
      mutant also possessing few large chloroplasts per cell, and arc1. Analysis of
      these double mutants shows that chloroplast number per mesophyll cell is greater
      when arc5 and arc3 mutations are expressed in the arc1 background than when
      expressed alone. The cell-specific nature of arc mutants was also analyzed. The
      phenotypic traits characteristic of arc3 and arc5 are a reduction in chloroplast
      number and an increase in chloroplast size in mesophyll cells: these changes are
      also observed in reduced form in the epidermal and guard cell chloroplasts of
      arc3 and arc5 plants. Analysis of parenchyma sheath cell chloroplasts suggests
      that in leaves of arc1 plants the normal developmental distinction between
      mesophyll and parenchyma sheath chloroplasts is perturbed. The relevance of these
      findings to the analysis of the control of chloroplast division in mesophyll
      cells is discussed.

PMID- 12232073
TI  - Plant Defense Response to Fungal Pathogens (Activation of Host-Plasma Membrane H+
      ATPase by Elicitor-Induced Enzyme Dephosphorylation).
AB  - Elicitor preparations containing the avr5 gene products from race 4 of
      Cladosporium fulvum and tomato (Lycopersicon esculentum L.) cells near isogenic
      for the resistance gene Cf5 were used to investigate events following the
      treatment of host plasma membranes with elicitor. A 4-fold increase in H+-ATPase
      activity, coincident with the acidification of the extracellular medium, was
      detected immediately after elicitor treatment. The elicitor-induced stimulation
      of the plasma membrane H+-ATPase was inhibited by okadaic acid but not by
      staurosporine, suggesting that protein dephosphorylation was required for
      increased H+-ATPase activity. This observation was confirmed by [gamma]-32P
      labeling and immunodetection of the plasma membrane H+-ATPase. Effects of
      guanidine nucleotide analogs and mastoparan on the ATPase activity suggested the
      role of GTP-binding proteins in mediating the putative elicitor-receptor binding,
      resulting in activation of a phosphatase(s), which in turn stimulates the plasma
      membrane H+-ATPase by dephosphorylation.

PMID- 12232074
TI  - Composition and Distribution of Adenylates in Soybean (Glycine max L.) Nodule
      Tissue.
AB  - Adenylates (ATP, ADP, and AMP) may play a central role in the regulation of the
      O2-limited C and N metabolism of soybean nodules. To be able to interpret
      measurements of adenylate levels in whole nodules and to appreciate the
      significance of observed changes in adenylates associated with changes in O2
      limited metabolism, methods were developed for measuring in vivo levels of
      adenylate pools in the cortex, plant central zone, and bacteroid fractions of
      soybean (Glycine max L. Merr cv Maple Arrow x Bradyrhizobium japonicum strain
      USDA 16) nodules. Intact nodulated roots were either frozen in situ by flushing
      with prechilled Freon-113(-156[deg]C) or by rapidly (<1 s) uprooting plants and
      plunging them into liquid N2. The adenylate energy charge (AEC = [ATP + 0.5 x
      ADP]/[ATP + ADP + AMP]) of whole-nodule tissue (0.65 [plus or minus] 0.01, n = 4)
      was low compared to that of subtending roots (0.80 [plus or minus] 0.03, n = 4),
      a finding indicative of hypoxic metabolism in nodules. The cortex and central
      zone tissues were dissected apart in lyophilized nodules, and AEC values were
      0.84 [plus or minus] 0.04 and 0.61 [plus or minus] 0.03, respectively. Although
      the total adenylate pool in the lyophilized nodules was only 41% of that measured
      in hydrated tissues, the AEC values were similar, and the lyophilized nodules
      were assumed to provide useful material for assessing adenylate distribution. The
      nodule cortex contained 4.4% of whole-nodule adenylates, with 95.6% being located
      in the central zone. Aqueous fractionation of bacteroids from the plant fraction
      of whole nodules and the use of marker enzymes or compounds to correct for
      recovery of bacteroids and cross-contamination of the bacteroid and plant
      fractions resulted in estimates that 36.2% of the total adenylate pool was in
      bacteroids, and 59.4% was in the plant fraction of the central zone. These are
      the first quantitative assessments of adenylate distribution in the plant and
      bacteroid fractions of legume nodules. These estimates were combined with
      theoretical calculations of rates of ATP consumption in the cortex (9.5 nmol g-1
      fresh weight of nodule s-1), plant central zone (38 nmol g-1 fresh weight of
      nodule s-1), and bacteroids (62 nmol g-1 fresh weight of nodule s-1) of soybean
      nodules to estimate the time constants for turnover of the total adenylate pool
      and the ATP pool within each nodule fraction. The low values for time constant
      (1.6-5.8 s for total adenylate, 0.9-2.5 s for ATP only) in each fraction reflect
      the high metabolic activity of soybean nodules and provide a background for
      further studies of the role of adenylates in O2-limited nodule metabolism.

PMID- 12232075
TI  - The Effects of Illumination on the Xanthophyll Composition of the Photosystem II
      Light-Harvesting Complexes of Spinach Thylakoid Membranes.
AB  - The xanthophyll composition of the light-harvesting chlorophyll a/b proteins of
      photosystem II (LHCII) has been determined for spinach (Spinacia oleracea L.)
      leaves after dark adaptation and following illumination under conditions
      optimized for conversion of violaxanthin into zeaxanthin. Each of the four LHCII
      components was found to have a unique xanthophyll composition. The major
      carotenoid was lutein, comprising 60% of carotenoid in the bulk LHCIIb and 35 to
      50% in the minor LHCII components LHCIIa, LHCIIc, and LHCIId. The percent of
      carotenoid found in the xanthophyll cycle pigments was approximately 10 to 15% in
      LHCIIb and 30 to 40% in LHCIIa, LHCIIc, and LHCIId. The xanthophyll cycle was
      active for the pigments bound to all of the LHCII components. The extent of
      deepoxidation for complexes prepared from light-treated leaves was 27, 65, 69,
      and 43% for LHCIIa, -b, -c, and -d, respectively. These levels of conversion of
      violaxanthin to zeaxanthin were found in LHCII prepared by three different
      isolation procedures. It was estimated that approximately 50% of the zeaxanthin
      associated with photosystem II is in LHCIIb and 30% is associated with the minor
      LHCII components.

PMID- 12232076
TI  - Transient Responses of Cell Turgor and Growth of Maize Roots as Affected by
      Changes in Water Potential.
AB  - Transient responses of cell turgor (P) and root elongation to changes in water
      potential were measured in maize (Zea mays L.) to evaluate mechanisms of
      adaptation to water stress. Changes of water potential were induced by exposing
      roots to solutions of KCl and mannitol (osmotic pressure about 0.3 MPa). Prior to
      a treatment, root elongation was about 1.2 mm h-1 and P was about 0.67 MPa across
      the cortex of the expansion zone (3-10 mm behind the root tip). Upon addition of
      an osmoticum, P decreased rapidly and growth stopped completely at pressure below
      approximately 0.6 MPa, which indicated that the yield threshold (Ytrans,1) was
      just below the initial turgor. Turgor recovered partly within the next 30 min and
      reached a new steady value at about 0.53 MPa. The root continued to elongate as
      soon as P rose above a new threshold (Ytrans,2) of about 0.45 MPa. The time
      between Ytrans,1 and Ytrans,2 was about 10 min. During this transition turgor
      gradients of as much as 0.15 MPa were measured across the cortex. They resulted
      from a faster rate of turgor recovery of cells deeper inside the tissue compared
      with cells near the root periphery. Presumably, the phloem was the source of the
      compounds for the osmotic adjustment. Turgor recovery was restricted to the
      expansion zone, as was confirmed by measurements of pressure kinetics in mature
      root tissue. Withdrawal of the osmoticum caused an enormous transient increase of
      elongation, which was related to only a small initial increase of P. Throughout
      the experiment, the relationship between root elongation rate and turgor was
      nonlinear. Consequently, when Y were calculated from steady-state conditions of P
      and root elongation before and after the osmotic treatment, Yss was only 0.21 MPa
      and significantly smaller compared with the values obtained from direct
      measurements (0.42-0.64 MPa). Thus, we strongly emphasize the need for
      measurements of short-term responses of elongation and turgor to determine cell
      wall mechanics appropriately. Our results indicate that the rate of solute flow
      into the growth zone could become rate-limiting for cell expansion under
      conditions of mild water stress.

PMID- 12232077
TI  - Phytochelatins in Cadmium-Sensitive and Cadmium-Tolerant Silene vulgaris (Chain
      Length Distribution and Sulfide Incorporation).
AB  - In response to a range of Cd concentrations, the root tips of Cd-tolerant plants
      of Silene vulgaris exhibit a lower rate of PC production accompanied by a lower
      rate of longer chain PC synthesis than those of Cd-sensitive plants. At the same
      Cd exposure level, stable PC-Cd complexes are more rapidly formed in the roots of
      Cd-sensitive plants than in those of tolerant plants. At an equal PC
      concentration in the roots, the PC composition and the amount of sulfide
      incorporated per unit of PC-thiol is the same in both populations. Although these
      compounds might play some role in mechanisms that contribute to Cd
      detoxification, the ability to produce these compounds in greater amounts is not,
      itself, the mechanism that produces increased Cd tolerance in tolerant S.
      vulgaris plants.

PMID- 12232078
TI  - Nutrient Uptake Changes in Ascorbate Free Radical-Stimulated Onion Roots.
AB  - Long-term treatments with ascorbate free radical-stimulated glucose, fucose,
      sucrose, and nitrate uptake in Allium cepa roots. Glucose and fucose showed
      saturation kinetics in untreated roots, but after treatment with the ascorbate
      free radical, uptake was linear with time. Although the rates of nitrate and
      sucrose uptake increased after treatment with ascorbate free radical, the
      kinetics were similar to those observed in the controls. Ascorbate and
      dehydroascorbate inhibited nutrient uptake. The uptake rates for all nutrients
      increased throughout the 48-h period of pretreatment with ascorbate free radical.
      During the treatment an increase in the vacuole volume and tonoplast surface area
      also occurred. These results show the relationship between an increase in
      vacuolar volume and stimulated nutrient uptake from ascorbate-free radical,
      resulting in enhanced root elongation. These results suggest that activation of a
      transplasma membrane redox system by ascorbate-free radical is involved in these
      responses.

PMID- 12232079
TI  - Decapitation Reduces the Metabolism of Gibberellin A20 to A1 in Pisum sativum L.,
      Decreasing the Le/le Difference.
AB  - When the metabolism of [13C,3H]gibberellin (GA)20 in Pisum sativum L. was
      investigated using decapitated plants and stem sections, no evidence was obtained
      for the recently postulated inhibitor of GA20 3[beta]-hydroxylase (V.A. Smith
      [1992] Plant Physiol 99: 372-377). Instead, the results are consistent with the
      hypothesis that the mutation le reduces GA1 production by altering the structure
      or level of the 3[beta]-hydroxylase.

PMID- 12232080
TI  - Loss of Microtubules in the Interphase Cells of Onion (Allium cepa L.) Root Tips
      from the Cell Cortex and Their Appearance in the Cytoplasm after Treatment with
      Cycloheximide.
AB  - As part of a project to investigate the mechanism of cortical microtubule (MT)
      alignment, we examined the effects of cycloheximide (CHM) on cortical MTs in the
      root tip cells of Allium cepa L. Results show that although a preprophase band of
      MTs remained in the cell cortex, interphase MTs disappeared from the cortical
      cytoplasm and then appeared concomitantly in the inner cytoplasm when the rate of
      de novo protein synthesis was reduced with CHM (11-360 [mu]M for 2 h)

PMID- 12232081
TI  - How Do Chemical Signals Work in Plants that Grow in Drying Soil?

PMID- 12232082
TI  - Covalent Cross-Links in the Cell Wall.

PMID- 12232083
TI  - Chromoplast Biogenesis in Cucumis sativus Corollas (Rapid Effect of Gibberellin
      A3 on the Accumulation of a Chromoplast-Specific Carotenoid-Associated Protein).
AB  - The development of cucumber (Cucumis sativus L.) corollas is accompanied by the
      accumulation of chromoplasts. In mature corollas, chromoplasts, but no
      chloroplasts, were detected by electron microscopy. Chlorophyll was also
      undetectable in corollas at anthesis. The contents of carotenoids and a
      carotenoid-associated, chromoplast-specific, 35-kD protein in corollas increased
      in parallel with flower development, peaking concomitantly at anthesis. The
      involvement of phytohormones and light in the regulation of their expression was
      studied. When gibberellin A3 (GA3) was added to an in vitro bud culture system,
      accumulation of both carotenoids and the 35-kD protein was markedly enhanced. The
      specific up-regulation of the 35-kD protein was very rapid: after only 2 h of
      culture, increased levels were detected in GA3-treated versus untreated corollas.
      During this period, corolla fresh weight and total protein and carotenoid
      contents remained unchanged. Inclusion of abscisic acid in the culture medium
      counteracted the effect of GA3. Accumulation of the 35-kD protein was also
      enhanced when flower buds on plants were sprayed with GA3 or etiolated.

PMID- 12232084
TI  - A Peanut Nodule Lectin in Infected Cells and in Vacuoles and the Extracellular
      Matrix of Nodule Parenchyma.
AB  - Root nodules on peanut (Arachis hypogaea L.) accumulate a galactose/lactose
      binding lectin that is similar, but not identical, to the major seed lectin in
      peanut. The function of the peanut nodule lectin (PNL) is not known. In the
      current study, we have investigated the location of lectin in the nodule using
      immunogold labeling and enzyme-linked immunosorbant assays (ELISA). Lectin was
      most abundant in the nodule parenchyma, where it accumulated in vacuoles,
      suggesting a possible role as a vegetative storage protein. Lectin was also
      detected in the extracellular matrix in the nodule parenchyma, a location that
      corresponds to the tissue layer forming a barrier to oxygen diffusion. The
      potential for interactions between PNL and other cell wall components, including
      a previously described high-molecular weight glycoprotein that co-localizes with
      PNL, is discussed. Within infected cells, lectin was not detectable by immunogold
      labeling within the cytoplasm, but light labeling was suggestive of lectin
      localization within the symbiosome lumen. Analysis of fractionated symbiosomes by
      the more sensitive ELISA technique confirmed that lectin was present within the
      symbiosome, but was not bound to bacteroids. Our results indicate that PNL
      probably plays several roles in this nitrogen-fixing symbiosis.

PMID- 12232085
TI  - A Role for Cytokinins in De-Etiolation in Arabidopsis (det Mutants Have an
      Altered Response to Cytokinins).
AB  - When grown in the absence of light, Arabidopsis thaliana deetiolated (det)
      mutants develop many of the characteristics of light-grown plants, including the
      development of leaves and chloroplasts, the inhibition of hypocotyl growth
      elongation, and elevated expression levels of light-regulated genes. We show here
      that dark-grown wild-type seedlings exhibit similar phenotypic traits if any one
      of a variety of cytokinins are present in the growth medium. We further show that
      the striking phenotype of det mutants is unlikely to be caused by different
      levels of cytokinins in these mutants. The three major Arabidopsis cytokinins,
      zeatin, zeatin riboside, and isopentenyladenosine, accumulate to similar levels
      in wild-type seedlings grown in either the light or the dark. There is no
      consistently different pattern for the levels of these cytokinins in wild-type
      versus det1 or det2 mutants. However, det1 and det2 have an altered response to
      cytokinin in a detached leaf senescence assay and in tissue culture experiments.
      A model is proposed in which light and cytokinins act independently or
      sequentially through common signal transduction intermediates such as DET1 and
      DET2 to control the downstream light-regulated responses.

PMID- 12232086
TI  - Genetic Manipulation of the Cyanobacterium Synechocystis sp. PCC 6803
      (Development of Strains Lacking Photosystem I for the Analysis of Mutations in
      Photosystem II).
AB  - We have taken a genetic approach to eliminating the presence of photosystem I
      (PSI) in site-directed mutants of photosystem II (PSII) in the cyanobacterium
      Synechocystis sp. PCC 6803. By selecting under light-activated heterotrophic
      conditions, we have inactivated the psaA-psaB operon encoding the PSI reaction
      center proteins in cells containing deletions of the three psbA genes. We have
      also introduced deletions into both copies of psbD in a strain containing a
      mutation that inactivates psaA (ADK9). These strains, designated D1-/PSI- and D2
      /PSI-, may serve as recipient strains for the incorporation of site-directed
      mutations in either psbA2 or psbD1. The characterization of these cells, which
      lack both PSI and PSII, is described.

PMID- 12232087
TI  - Direct and Indirect Effects of Atmospheric Carbon Dioxide Enrichment on Leaf
      Respiration of Glycine max (L.) Merr.
AB  - Long-term and short-term effects of CO2 enrichment on dark respiration were
      investigated using soybean (Glycine max [L.] Merr.) plants grown at either 35.5
      or 71.0 Pa CO2. Indirect effects, or effects of growth in elevated CO2, were
      examined using a functional model that partitioned respiration into growth and
      maintenance components. Direct effects, or immediate effects of a short-term
      change in CO2, were examined by measuring dark respiration, first, at the CO2
      partial pressure at which plants were grown, and second, after equilibration in
      the reciprocal CO2 partial pressure. The functional component model indicated
      that the maintenance coefficient of respiration increased 34% with elevated CO2,
      whereas the growth coefficient was not significantly affected. Changes in
      maintenance respiration were correlated with a 33% increase in leaf total
      nonstructural carbohydrate concentration, but leaf nitrogen content of soybean
      leaves was not affected by CO2 enrichment. Thus, increased maintenance
      respiration may be a consequence of increased nonstructural carbohydrate
      accumulation. When whole soybean plants were switched from low CO2 to high CO2
      for a brief period, leaf respiration was always reduced. However, this direct
      effect of CO2 partial pressure was approximately 50% less in plants grown in
      elevated CO2. We conclude from this study that there are potentially important
      effects of CO2 enrichment on plant respiration but that the effects are different
      for plants given a short-term increase in CO2 partial pressure versus plants
      grown in elevated CO2.

PMID- 12232088
TI  - The Induction of Seed Germination in Arabidopsis thaliana Is Regulated
      Principally by Phytochrome B and Secondarily by Phytochrome A.
AB  - We examined whether spectrally active phytochrome A (PhyA) and phytochrome B
      (PhyB) play specific roles in the induction of seed germination in Arabidopsis
      thaliana (L.) Heynh., using PhyA- and PhyB-null mutants, fre1-1 (A. Nagatani,
      J.W. Reed, J. Chory [1993] Plant Physiol 102: 269-277) and hy3-Bo64 (J. Reed,
      P.Nagpal, D.S. Poole, M. Furuya, J. Chory [1993] Plant Cell 5: 147-157). When
      dormant seeds of each genotype imbibed in the dark on aqueous agar plates, the
      hy3 (phyB) mutant did not germinate, whereas the fre1 (phyA) mutant germinated at
      a rate of 50 to 60%, and the wild type (WT) germinated at a rate of 60 to 70%. By
      contrast, seeds of all genotypes germinated to nearly 100% when plated in
      continuous irradiation with white or red light. When plated in continuous far-red
      light, however, frequencies of seed germination of the WT and the fre1 and hy3
      mutants averaged 14, nearly 0, and 47%, respectively, suggesting that PhyB in the
      red-absorbing form prevents PhyA-dependent germination under continuous far-red
      light. When irradiated briefly with red or far-red light after imbibition for 1
      h, a typical photoreversible effect on seed germination was observed in the fre1
      mutant and the WT but not in the hy3 mutant. In contrast, when allowed to imbibe
      in the dark for 24 to 48 h and exposed to red light, the seed germination
      frequencies of the hy3 mutant were more than 40%. Immunoblot analyses of the
      mutant seeds showed that PhyB apoprotein accumulated in dormant seeds of the WT
      and the fre1 mutant as much as in the seeds that had imbibed. In contrast, PhyA
      apoprotein, although detected in etiolated seedlings grown in the dark for 5 d,
      was not detectable in the dormant seeds of the WT and the hy3 mutant. The above
      physiological and immunochemical evidence indicates that PhyB in the far-red
      absorbing form was stored in the Arabidopsis seeds and resulted in germination in
      the dark. Hence, PhyA does not play any role in dark germination but induces
      germination under continuous irradiation with far-red light. Finally, we examined
      seeds from a signal transduction mutant, det1, and a det1/hy3 double mutant. The
      det1 seeds exhibited photoreversible responses of germination on aqueous agar
      plates, and the det1/hy3 double mutant seeds did not. Hence, DET1 is likely to
      act in a distinct pathway from PhyB in the photoregulation of seed germination.

PMID- 12232089
TI  - Folate Metabolism in Datura innoxia (In Vivo and in Vitro Folylpolyglutamate
      Synthesis in Wild-Type and Methotrexate-Resistant Cells).
AB  - In vivo folylpolyglutamate pools of the wild-type (Px4) and methotrexate
      resistant (MTX161) Datura innoxia cell lines were detected by incorporation of
      [14C]p-aminobenzoate into folates. The folylpolyglutamate derivatives were
      cleaved to p-aminobenzoylpolyglutamates and separated according to glutamyl chain
      length by high-performance liquid chromatography. Hexaglutamates were the
      predominant form in both Datura cell lines. The proportions of individual
      folylpolyglutamates were unaffected by culturing the cells in medium containing
      products of one-carbon metabolism such as glycine, adenine, thymidine, or
      methionine. Radiolabeling of the hexaglutamates was greatly reduced in the
      presence of 10-8 M methotrexate (MTX) in the Px4 cells but not in the MTX161
      cells. Tetrahydrofolate, 5, 10-methylenetetrahydrofolate, and folinic acid were
      effective substrates for the folylpolyglutamate synthetase from Datura cells in
      vitro, whereas MTX and folate were poor substrates. In vivo, MTX can be slowly
      converted into its polyglutamate derivatives up to MTXGlu4 or MTXGlu5 in Datura
      cells in the longer term. Significantly lower levels of MTX polyglutamates in
      MTX161 cells were found compared with those of Px4 cells during prolonged (10 d)
      exposure to MTX. Although in vivo and in vitro folylpolyglutamate synthesis was
      found to be similar in both cell lines, about a 4-fold increase in specific
      activity of [gamma]-glutamyl hydrolase (GGH) was detected in the MTX161 cell
      line. The increase in GGH in the resistant cells suggested that breakdown of
      polyglutamylated forms of MTX may play a role in acquired MTX resistance.

PMID- 12232090
TI  - Modification of the Cellular Heat Sensitivity of Cucumber by Growth under
      Supplemental Ultraviolet-B Radiation.
AB  - The effect of ultraviolet B (UV-B) radiation on the thermal sensitivity of
      cucumber (Cucumis sativus L.) was studied using UV-B-sensitive cv Poinsett 76 and
      UV-B-resistant cv Ashley grown under control and elevated (300 mW m-2) UV-B
      radiation levels. Using both cotyledon and leaf discs, the ability of the tissue
      to reduce triphenyl tetrazolium chloride (TTC) was determined after treatment at
      50[deg]C for various times. Semilogarithmic plots of TTC reduction as a function
      of time at 50[deg]C were curvilinear. They were monophasic for the control
      cucumber and biphasic for cucumber grown in the presence of elevated UV-B.
      Treatment of cucumber plants at 37[deg]C for 24 h or of tissue discs at acute UV
      B levels for 1 h further modified their response to elevated temperature. These
      results suggest that growth of cucumber under enhanced UV-B radiation levels
      increased its ability to withstand elevated temperatures.

PMID- 12232091
TI  - Development of Endopeptidase Activities in Maize (Zea mays L.) Endosperms.
AB  - An activity stain was used after native polyacrylamide gel electrophoresis, and
      at least 17 different endopeptidase activities were detected in maize (Zea mays
      L.) endosperm extracts prepared during the first 6 d after imbibition. The
      enzymes detected were classified into four groups based on their time of
      appearance and on their mobility in polyacrylamide gels. The first group, which
      included two enzymes present in dry endosperms, disappeared soon after
      imbibition. The second group, comprising five activity bands, appeared during the
      first 2 to 3 d after imbibition and then disappeared. The third set of enzymes
      increased continuously throughout the experimental period. The fourth group
      appeared after d 3 and remained at a constant level after that time. The
      endopeptidase activities were characterized by the effect of specific inhibitors
      on their activities. The two enzymes of the first group are metalloendopeptidases
      based on their sensitivity to ethylenediaminetetracetate (EDTA). Enzymes of the
      second, third, and fourth groups are sulfhydryl-endopeptidases as judged by their
      sensitivity to antipain, chymostatin, leupeptin, and E-64 and by their
      requirement for 2-mercaptoethanol. Pepstatin, phenylmethylsulfonyl fluoride, or
      EDTA had no effect on these enzymes. Many of the second, third, and fourth group
      enzymes cleaved [alpha]-zein-rich proteins as well as such easily obtained
      proteins as gelatin (used in our standard assay) and hemoglobin. The second group
      had a high affinity for [gamma]-zein, whereas none of the bands in the fourth
      group of enzymes cleaved this type of zein. The two metalloenzymes of the first
      group cleaved neither [alpha]- nor [gamma]-zeins.

PMID- 12232092
TI  - Photosynthetic Acclimation to Elevated CO2 Occurs in Transformed Tobacco with
      Decreased Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase Content.
AB  - Inhibition of net carbon assimilation rates during growth at elevated CO2 was
      studied in transgenic tobacco (Nicotiana tabacum L.) plants containing zero to
      two copies of antisense DNA sequences to the small subunit polypeptide (rbcS)
      gene of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). High- and low
      Rubisco tobacco plants were obtained from the selfed progeny of the original line
      3 transformant (S.R. Rodermel, M.S. Abbott, L. Bogorad [1988] Cell 55: 673-681).
      Assimilation rates of high- and low-Rubisco tobacco plants increased 22 and 71%,
      respectively, when transferred from 35- to 70-Pa CO2 chamber air at 900 [mu]mol m
      2 s-1 photon flux density. However, CO2-dependent increases of net carbon
      assimilation rates of high- and low-Rubisco plants virtually disappeared after 9
      d of growth in elevated CO2 chamber air. Total above-ground dry matter production
      of high- and low-Rubisco plants was 28 and 53% greater, respectively, after 9 d
      of growth at 70 Pa compared with 35 Pa CO2. Most of this dry weight gain was due
      to increased specific leaf weight. Rubisco activity, Rubisco protein, and total
      chlorophyll were lower in both high- and low-Rubisco plants grown in enriched
      compared with ambient CO2 chamber air. Soluble leaf protein also decreased in
      response to CO2 enrichment in high- but not in low-Rubisco tobacco plants.
      Decreased Rubisco activities in CO2-adapted high- and low-Rubisco plants were not
      attributable to changes in activation state of the enzyme. Carbonic anhydrase
      activities and subunit levels measured with specific antibodies were similar in
      high- and low-Rubisco tobacco plants and were unchanged by CO2 enrichment.
      Collectively, these findings suggested that photosynthetic acclimation to
      enriched CO2 occurred in tobacco plants either with or without transgenically
      decreased Rubisco levels and also indicated that the down-regulation of Rubisco
      in CO2-adapted tobacco plants was related to decreased specific activity of this
      enzyme.

PMID- 12232093
TI  - Occurrence of Only One Form of Glutamine Synthetase in the Green Alga
      Monoraphidium braunii.
AB  - Anion-exchange chromatography of crude extracts from the green alga Monoraphidium
      braunii yielded two glutamine synthetase (GS) activities. The ratio of activities
      was markedly different when crude extracts were subjected to various processing
      conditions but was not influenced by environmental factors of cell cultures.
      However, high performance liquid chromatography anion-exchange chromatograms
      showed only one GS if the crude extracts were processed immediately after cell
      disruption. Moreover, standard chromatography of crude extracts obtained in the
      absence of dithioerythritol, a reductant generally used in disruption buffers,
      yielded a single activity peak. Enzyme samples from the two activities obtained
      in the presence of dithioerythritol were purified for physicochemical
      characterization and antibody production. Both enzyme samples exhibited similar
      reactions to different inactivating agents and were undistinguishable by size
      exclusion chromatography and native polyacrylamide gel electrophoresis.
      Additionally, the two GS preparations showed absolute antigenic identity as
      demonstrated by immunodiffusion and immunoblotting experiments.
      Immunocytochemistry of M. braunii cryosections evidenced a chloroplast-specific
      distribution of the enzyme, which rules out the existence of a cytoplasmic
      counterpart. All these results support the proposal that M. braunii possesses
      only one form of GS.

PMID- 12232094
TI  - Development of Desiccation Tolerance during Embryogenesis in Rice (Oryza sativa)
      and Wild Rice (Zizania palustris) (Dehydrin Expression, Abscisic Acid Content,
      and Sucrose Accumulation).
AB  - The ability of seeds to withstand desiccation develops during embryogenesis and
      differs considerably among species. Paddy rice (Oryza sativa L.) grains readily
      survive dehydration to as low as 2% water content, whereas North American wild
      rice (Zizania palustris var interior [Fasset] Dore) grains are not tolerant of
      water contents below 6% and are sensitive to drying and imbibition conditions.
      During embryogenesis, dehydrin proteins, abscisic acid (ABA), and saccharides are
      synthesized, and all have been implicated in the development of desiccation
      tolerance. We examined the accumulation patterns of dehydrin protein, ABA, and
      soluble saccharides (sucrose and oligosaccharides) of rice embryos and wild rice
      axes in relation to the development of desiccation tolerance during
      embryogenesis. Dehydrin protein was detected immunologically with an antibody
      raised against a conserved dehydrin amino acid sequence. Both rice and wild rice
      embryos accumulated a 21-kD dehydrin protein during development, and an
      immunologically related 38-kD protein accumulated similarly in rice. Dehydrin
      protein synthesis was detected before desiccation tolerance had developed in both
      rice embryos and wild rice axes. However, the major accumulation of dehydrin
      occurred after most seeds of both species had become desiccation tolerant. ABA
      accumulated in wild rice axes to about twice the amount present in rice embryos.
      There were no obvious relationships between ABA and the temporal expression
      patterns of dehydrin protein in either rice or wild rice. Wild rice axes
      accumulated about twice as much sucrose as rice embryos. Oligosaccharides were
      present at only about one-tenth of the maximum sucrose concentrations in both
      rice and wild rice. We conclude that the desiccation sensitivity displayed by
      wild rice grains is not due to an inability to synthesize dehydrin proteins, ABA,
      or soluble carbohydrates.

PMID- 12232095
TI  - Sucrose Modulation of Soybean Vsp Gene Expression Is Inhibited by Auxin.
AB  - We have shown that auxin represses soybean (Glycine max L.) vegetative storage
      protein gene (Vsp) expression in suspension-cultured cells and in leaves and
      petioles of excised trifoliates. The auxin analog naphthyleneacetic acid (NAA) at
      10 [mu]M strongly inhibited methyl jasmonate-induced Vsp expression in soybean
      suspension-cultured cells. Both indole-3-acetic acid and NAA inhibited methyl
      jasmonate- and wound-induced expression of the Vsp and LoxA excised soybean
      trifoliate leaves and petioles. The less active auxin analog phenylacetic acid
      had less effect on methyl jasmonate- and wound-induced expression of these genes.
      Addition of cytokinin to alter the auxin:cytokinin ratio did not reverse auxin
      inhibition of Vsp expression. Transcription of [beta]-glucuronidase (Gus)
      modulated by a methyl jasmonate-responsive domain derived from the VspB promoter
      was minimally influenced by auxin. In contract, sucrose-induced expression of Gus
      mediated by a sucrose-responsive domain of the VspB promoter was strongly
      inhibited by NAA. We conclude that auxin inhibits Vsp mRNA accumulation, in part,
      by repressing sugar-mediated activation of Vsp expression.

PMID- 12232096
TI  - A Comparison of Freezing Injury in Oat and Rye: Two Cereals at the Extremes of
      Freezing Tolerance.
AB  - A detailed analysis of cold acclimation of a winter rye (Secale cereale L. cv
      Puma), a winter oat (Avena sativa L. cv Kanota), and a spring oat cultivar (Ogle)
      revealed that freezing injury of leaves of nonacclimated seedlings occurred at 
      2[deg]C in both the winter and spring cultivars of oat but did not occur in
      winter rye leaves until after freezing at -4[deg]C. The maximum freezing
      tolerance was attained in all cultivars after 4 weeks of cold acclimation, and
      the temperature at which 50% electrolyte leakage occurred decreased to -8[deg]C
      for spring oat, -10[deg]C for winter oat, and -21[deg]C for winter rye. In
      protoplasts isolated from leaves of nonacclimated spring oat, expansion-induced
      lysis was the predominant form of injury over the range of -2 to -4[deg]C. At
      temperatures lower than -4[deg]C, loss of osmotic responsiveness, which was
      associated with the formation of the hexagonal II phase in the plasma membrane
      and subtending lamellae, was the predominant form of injury. In protoplasts
      isolated from leaves of cold-acclimated oat, loss of osmotic responsiveness was
      the predominant form of injury at all injurious temperatures; however, the
      hexagonal II phase was not observed. Rather, injury was associated with the
      occurrence of localized deviations of the plasma membrane fracture plane to
      closely appressed lamellae, which we refer to as the "fracture-jump lesion."
      Although the freeze-induced lesions in the plasma membrane of protoplasts of
      spring oat were identical with those reported previously for protoplasts of
      winter rye, they occurred at significantly higher temperatures that correspond to
      the lethal freezing temperature.

PMID- 12232097
TI  - A Contrast of the Plasma Membrane Lipid Composition of Oat and Rye Leaves in
      Relation to Freezing Tolerance.
AB  - The lipid composition of the plasma membrane isolated from leaves of spring oat
      (Avena sativa L. cv Ogle) was vastly different from that of winter rye (Secale
      cereale L. cv Puma). The plasma membrane of spring oat contained large
      proportions of phospholipids (28.8 mol% of the total lipids), cerebrosides (27.2
      mol%), and acylated sterylglucosides (27.3 mol%) with lesser proportions of free
      sterols (8.4 mol%) and sterylglucosides (5.6 mol%). In contrast, the plasma
      membrane of winter rye contained a greater proportion of phospholipids (36.6
      mol%), and there was a lower proportion of cerebrosides (16.4 mol%); free sterols
      (38.1 mol%) were the predominant sterols, with lesser proportions of
      sterylglucosides (5.6 mol%) and acylated sterylglucosides (2.9 mol%). Although
      the relative proportions of individual phospholipids, primarily
      phosphatidylcholine and phosphatidylethanolamine, and the molecular species of
      these two phospholipids were similar in oat and rye, the relative proportions of
      di-unsaturated species of these two phospholipids were substantially lower in oat
      than in rye. The relative proportions of sterol species in oat were different
      from those in rye; the molecular species of cerebrosides were similar in oat and
      rye, with only slight differences in the proportions of the individual species.
      After 4 weeks of cold acclimation, the proportion of phospholipids increased
      significantly in both oat (from 28.8 to 36.8 mol%) and rye (from 36.6 to 43.3
      mol%) as a result of increases in the proportions of phosphatidylcholine and
      phosphatidylethanolamine. For both oat and rye, the relative proportions of di
      unsaturated species increased after cold acclimation, but the increase was
      greater in rye than in oat. In both oat and rye, this increase occurred largely
      during the first week of cold acclimation. During the 4 weeks of cold
      acclimation, there was a progressive decrease in the proportion of cerebrosides
      in the plasma membrane of rye (from 16.4 to 10.5 mol%), but there was only a
      small decrease in oat (from 27.2 to 24.2 mol%). In both oat and rye, there were
      only small changes in the proportions of free sterols and sterol derivatives
      during cold acclimation. Consequently, the proportions of both acylated
      sterylglucosides and cerebrosides remained substantially higher in oat than in
      rye after cold acclimation. The relationship between these differences in the
      plasma membrane lipid composition of oat and rye and their freezing tolerance is
      presented.

PMID- 12232098
TI  - Expression of a Soybean (Glycine max [L.] Merr.) Seed Storage Protein Gene in
      Transgenic Arabidopsis thaliana and Its Response to Nutritional Stress and to
      Abscisic Acid Mutations.
AB  - Among the three subunits of [beta]-conglycinin, the 7S seed storage protein of
      soybean (Glycine max [L.] Merr.), expression of the [beta] subunit gene is
      unique. Accumulation of the [beta] subunit is enhanced in sulfate-deficient
      soybean plants, and its mRNA levels increase when abscisic acid (ABA) is added to
      the in vitro cotyledon culture medium. Transgenic Arabidopsis thaliana lines
      carrying a gene encoding the [beta] subunit was constructed and grown under
      sulfate deficiency. Accumulation of both [beta] subunit mRNA and protein were
      enhanced in developing A. thaliana seeds. Accumulation of one of the A. thaliana
      seed storage protein mRNAs was also enhanced by sulfate deficiency, although the
      response was weaker than that observed for the soybean [beta] subunit mRNA. When
      the aba1-1 or abi3-1 mutations were crossed into the transgenic A. thaliana line,
      accumulation of the [beta] subunit was significantly reduced, whereas
      accumulation of the A. thaliana seed storage protein was not greatly affected.
      These results indicate that soybean and A. thaliana share a common mechanism for
      response to sulfate deficiency and to ABA, although the sensitivity is different
      between the species. The transgenic A. thaliana carrying the [beta] subunit gene
      of [beta]-conglycinin will be a good system to analyze these responses.

PMID- 12232099
TI  - Investigation of Gene Expression, Growth Kinetics, and Wall Extensibility during
      Brassinosteroid-Regulated Stem Elongation.
AB  - Brassinosteroids promote stem elongation in a variety of plants but little is
      known about the mechanism of action of these plant growth regulators. We
      investigated a number of physiological and molecular parameters associated with
      brassinosteroid-enhanced elongation. Continuous growth recordings of soybean
      (Glycine max L. cv Williams 82) epicotyls showed that there was a 45-min lag
      before 0.1 [mu]M brassinolide (BR) exerted a detectable effect on elongation. BR
      caused a marked increase in Instron-measured plastic extensibility, suggesting
      that BR may promote elongation in part by altering mechanical properties of the
      cell wall (wall loosening). Structure-function studies suggested that the
      dimensions of the brassinosteroid side chain were critical for promotion of
      elongation and expression of BRU1, a gene regulated specifically by active
      brassinosteroids. Auxin-BR interactions were examined by using small auxin up RNA
      (SAUR) gene probes and the auxin-insensitive diageotropica (dgt) mutant of tomato
      (Lycopersicon esculentum Mill.). We have shown that in wild-type tomato, which
      elongates in response to exogenous auxin, a transcript of identical size to the
      soybean SAUR 15A is strongly induced within 1 h by 50 [mu]M 2,4
      dichlorophenoxyacetic acid or indoleacetic acid, whereas in the dgt mutant, which
      does not elongate in response to auxin, no transcript is expressed. Furthermore,
      BR promotes equal elongation of hypocotyls in both wild-type and dgt tomatoes but
      does not rapidly induce the SAUR 15A homolog in either genotype. BR does not
      cause rapid induction of SAUR 6B in elongating soybean epicotyls but does lead to
      increased expression after 18 h. This late BR activation of SAUR 6B is
      controlled, at least in part, at the transcriptional level and is not accompanied
      by an increase of free indoleacetic acid in the tissue. We conclude that although
      both BR and auxin affect wall relaxation processes, BR-promoted elongation in
      soybean and tomato stems acts via a mechanism that most likely does not proceed
      through the auxin signal transduction pathway.

PMID- 12232100
TI  - Carbohydrate Status of Tulip Bulbs during Cold-Induced Flower Stalk Elongation
      and Flowering.
AB  - The effect of a cold treatment on the carbohydrate status of the scales and
      flower stalk of Tulipa gesneriana L. cv Apeldoorn bulbs during growth after
      planting was studied and compared with bulbs not given cold treatment. Bulbs were
      stored dry for 12 weeks at 5[deg]C (precooled) or 17[deg]C (noncooled). Only the
      5[deg]C treatment led to rapid flower stalk elongation and flowering following
      planting at higher temperatures. Precooling enhanced mobilization of starch,
      fructans, and sucrose in the scales. The cold-stimulated starch breakdown was
      initially accompanied by increased [alpha]-amylase activity per scale. In
      noncooled bulbs, [alpha]-amylase activity slightly decreased or remained more or
      less constant. Cold-induced flower stalk elongation was partially accompanied by
      a decrease in the sucrose content and an increase in the glucose content and
      invertase activity per g dry weight. The starch content in internodes initially
      decreased and subsequently increased; [alpha]-amylase activity per g dry weight
      of the lowermost internode showed a peak pattern during starch breakdown and
      increased thereafter. The internodes of noncooled bulbs, on the contrary,
      accumulated sucrose. Their glucose content and invertase activity per g dry
      weight remained low. Starch breakdown was not found and [alpha]-amylase activity
      per g dry weight of the lowermost internode remained at a low level. Precooling
      of tulip bulbs thus favors reserve mobilization in the scales and flower stalk
      and glucose accumulation in the elongating internodes.

PMID- 12232101
TI  - Carbon Isotope Discrimination, Gas Exchange, and Growth of Sugarcane Cultivars
      under Salinity.
AB  - Physiological features associated with differential resistance to salinity were
      evaluated in two sugarcane (Saccharum spp. hybrid) cultivars over an 8-week
      period during which greenhouse-grown plants were drip-irrigated with water or
      with NaCI solutions of 2, 4, 8, or 12 decisiemens (dS) m-1 electrical
      conductivity (EC). The CO2 assimilation rate (A), stomatal conductance (g), and
      shoot growth rate (SGR) began to decline as EC of the irrigation solution
      increased above 2 dS m-1. A, g, and SGR of a salinity-resistant cultivar (H69
      8235) were consistently higher than those of a salinity-susceptible cultivar (H65
      7052) at all levels of salinity and declined less sharply with increasing
      salinity. Carbon isotope discrimination ([delta]) in tissue obtained from the
      uppermost fully expanded leaf increased with salinity and with time elapsed from
      the beginning of the experiment, but [delta] was consistently lower in the
      resistant than in the susceptible cultivar at all levels of salinity. Gas
      exchange measurements suggested that variation in [delta] was attributable
      largely to variation in bundle sheath leakiness to CO2 ([phi]). Salinity-induced
      increases in [phi] appeared to be caused by a reduction in C3 pathway activity
      relative to C4 pathway activity rather than by physical changes in the
      permeability of the bundle sheath to CO2. A strong correlation between [delta]
      and A, g, and SGR permitted these to be predicted from [delta] regardless of the
      cultivar and salinity level. [delta] thus provided an integrated measure of
      several components of physiological performance and response.

PMID- 12232102
TI  - Following Suberization in Potato Wound Periderm by Histochemical and Solid-State
      13C Nuclear Magnetic Resonance Methods.
AB  - The time course of suberization in wound periderm from potato (Solanum tuberosum
      L.) has been monitored by histochemical and high-resolution solid-state nuclear
      magnetic resonance (NMR) methods. Light microscopy conducted after selective
      staining of the lipid and double-bonded constituents shows that suberin is
      deposited at the outermost intact cell-wall surface during the first 7 d of wound
      healing; suberization forms a barrier to tissue infiltration at later times.
      Cross polarization-magic angle spinning 13C NMR spectra demonstrate the
      deposition of a polyester containing all major suberin functional groups after
      just 4 d of wound healing. Initially the suberin includes a large proportion of
      aromatic groups and fairly short aliphatic chains, but the spectral data
      demonstrate the growing dominance of long-chain species during the period 7 to 14
      d after wounding. The results of preliminary 13C-labeling experiments with sodium
      [2-13C]acetate and DL-[1-13C]phenylalanine provide an excellent prospectus for
      future NMR-based studies of suberin biosynthesis.

PMID- 12232103
TI  - Temporal and Spatial Expression Pattern of Sucrose Synthase during Tomato Fruit
      Development.
AB  - Sucrose synthase is proposed to play an important role in the early stages of
      tomato fruit (Lycopersicon esculentum Mill.) growth. In this work, the temporal
      and spatial expression patterns of sucrose synthase during tomato fruit
      development were investigated. Fruit contained the majority of the sucrose
      synthase protein and mRNA relative to other organs. Only trace levels of sucrose
      synthase protein and mRNA were detected in the stem, petiole, and roots. Sucrose
      synthase mRNA was detected in pistils prior to anthesis, reached peak levels in
      fruit 5 to 7 d after anthesis (DAA), and was not detectable after 35 DAA. Sucrose
      synthase protein levels reached a maximum at 20 to 25 DAA and then declined to
      nondetectable levels after 45 DAA. The lack of coordination between protein and
      mRNA levels suggests that sucrose synthase expression may be controlled at the
      levels of both transcription and translation. Sucrose synthase mRNA was
      differentially localized in the fruit, being most abundant in the mesocarp cells
      adjacent to the placenta, the columella, and the cells surrounding the vascular
      bundle. Except around the vascular tissue, the localization of sucrose synthase
      mRNA positively correlates with starch granule accumulation at the cellular
      level.

PMID- 12232104
TI  - A Model of the Regulation of Nitrogenase Electron Allocation in Legume Nodules
      (II. Comparison of Empirical and Theoretical Studies in Soybean).
AB  - In N2-fixing legumes, the proportion of total electron flow through nitrogenase
      (total nitrogenase activity, TNA) that is used for N2 fixation is called the
      electron allocation coefficient (EAC). Previous studies have proposed that EAC is
      regulated by the competitive inhibition of H2 on N2 fixation and that the degree
      of H2 inhibition can be affected by a nodule's permeability to gas diffusion. To
      test this hypothesis, EAC was measured in soybean (Glycine max L. Merr.) nodules
      exposed to various partial pressures of H2 and N2, with or without changes in TNA
      or nodule permeability to gas diffusion, and the results were compared with the
      predictions of a mathematical model that combined equations for gas diffusion and
      competitive inhibition of N2 fixation (A. Moloney and D.B. Layzell [1993] Plant
      Physiol 103: 421-428). The empirical data clearly showed that decreases in EAC
      were associated with increases in external pH2, decreases in external pN2, and
      decreases in nodule permeability to O2 diffusion. The model predicted similar
      trends in EAC, and the small deviations that occurred between measured and
      predicted values could be readily accounted for by altering one or more of the
      following model assumptions: K1(H2) of nitrogenase (range from 2-4% H2), Km(N2)
      of nitrogenase (range from 4-5% N2), the allocation of less than 100% of whole
      nodule respiration to tissues within the diffusion barrier, and the presence of a
      diffusion pathway that is open pore versus closed pore. The differences in the
      open-pore and closed-pore versions of the model suggest that it may be possible
      to use EAC measurements as a tool for the study of legume nodule diffusion
      barrier structure and function. The ability of the model to predict EAC provided
      strong support for the hypothesis that H2 inhibition of N2 fixation plays a major
      role in the in vivo control of EAC and that the presence of a variable barrier to
      gas diffusion affects the H2 and N2 concentration in the infected cell and,
      therefore, the degree of H2 inhibition.

PMID- 12232105
TI  - Elicitor-Induced Cinnamyl Alcohol Dehydrogenase Activity in Lignifying Wheat
      (Triticum aestivum L.) Leaves.
AB  - The substrate-specific induction of wheat (Triticum aestivum L. cv Fenman) leaf
      cinnamyl alcohol dehydrogenase (CAD, EC 1.1.1.195) was examined in relation to
      its role in regulating the composition of defensive lignin induced at wound
      margins. Treatment of wounds with a partially acetylated chitosan hydrolysate or
      spores of the nonpathogen Botrytis cinerea elicited lignification at wound
      margins and invoked significant increases in phenylalanine ammonia-lyase (EC
      4.3.1.5), peroxidase (EC 1.11.1.7), and CAD activities. The substrate-specific
      induction of CAD with time was determined in elicitor-treated leaves and in
      excised lignifying wounds. In whole leaf extracts no significant increases in p
      cou-maryl and coniferyl alcohol dehydrogenase activities were detectable, but a
      significant 5-fold increase in sinapyl alcohol dehydrogenase activity was evident
      32 h after elicitor treatment. Similarly, fungal challenge resulted in elevated
      levels of only sinapyl alcohol dehydrogenase in whole-leaf extracts. In excised
      lignifying tissues p-coumaryl alcohol dehydrogenase levels were similar to those
      observed in healthy tissue. A small yet significant increase in coniferyl alcohol
      dehydrogenase was apparent, but the most dramatic increase occurred in sinapyl
      alcohol dehydrogenase activity, which increased to values approximately 10 times
      higher than the untreated controls. Our results show for the first time that CAD
      induction in lignifying tissues of wheat is predominantly attributable to highly
      localized increases in sinapyl alcohol dehydrogenase activity.

PMID- 12232106
TI  - The Unsaturation of Membrane Lipids Stabilizes Photosynthesis against Heat
      Stress.
AB  - The effect of the unsaturation of glycerolipids of thylakoid membranes on the
      heat tolerance of the photosynthetic evolution of oxygen was studied in vivo by
      mutation and transformation of fatty-acid desaturases in the cyanobacterium
      Synechocystis PCC6803. The experimental results indicate that elimination of
      dienoic lipid molecules decreases, to a small but distinct extent, the heat
      tolerance of photosynthetic oxygen evolution, but that elimination of trienoic
      lipid molecules has no effect on the heat tolerance. This conclusion contrasts
      with the previous hypothesis that the heat tolerance of photosynthesis is
      enhanced upon an increase in the level of saturation of membrane lipids. It is
      also shown that light does not affect the nature of the effect of lipid
      unsaturation on the heat tolerance of photosynthesis.

PMID- 12232107
TI  - Dark and Circadian Regulation of mRNA Accumulation in the Short-Day Plant
      Pharbitis nil.
AB  - The developmental transition of the meristem from vegetative to reproductive
      growth is controlled by the cyclic alternation of light and darkness in
      photoperiodic plants. Photoperiod is perceived in the leaves or cotyledons, where
      a flower-inducing signal is produced and transmitted to the apex. To begin to
      understand the molecular basis of the photoperiodic induction of flowering, we
      investigated changes in gene expression at the level of mRNA abundance that occur
      in association with dark induction of flowering in the short-day species
      Pharbitis nil. Several cDNAs were isolated that corresponded to mRNAs whose
      abundance is altered after the transition to darkness. The pattern of increase in
      mRNA levels corresponding to one cDNA clone, PN1, showed a dark-induced maximum
      at 8 h of darkness, whereas a second clone, PN9, showed a dark-induced
      accumulation of mRNA with peak levels at 12 to 16 h of darkness. When plants were
      held in continuous darkness, both PN1 and PN9 exhibited rhythmic patterns of mRNA
      accumulation with an approximate circadian periodicity, suggesting that their
      expression is under the control of an endogenous clock. The observed pattern of
      expression of PN1 and PN9 in cotyledon tissue was unusual in that darkness rather
      than light promoted mRNA accumulation, which is a temporal pattern of expression
      distinct from that of several other Pharbitis genes, including Cab, PsaG, and
      actin, whose mRNAs were most prevalent or equally prevalent in the light. Brief
      illumination of an inductive dark period by a red light night break strongly
      inhibited the accumulation of both PN1 and PN9 mRNA. The expression of both PN1
      and PN9 was spatially regulated in that mRNA transcripts were detected in the
      cotyledons and stems, but not the roots, of photoperiodically competent
      seedlings. Both PN1 and PN9 appeared to be present as single-copy genes in the
      Pharbitis genome. Sequence analysis has not determined the identity of these
      genes. Overall, the accumulation of mRNAs corresponding to both PN1 and PN9
      closely paralleled the process of photoperiodic floral induction in P. nil, but a
      clear involvement with this process cannot be established from our findings
      because of the difficulty of separating photoperiodic events from other light
      regulated processes, especially those involved in photosynthesis, such as Cab
      gene expression. These results identify the products of circadian-regulated genes
      in photoreceptive tissue of P. nil and support the concept that circadian
      regulated gene expression interacting with darkness may be involved in the
      regulation of photoperiodically controlled physiological processes, including
      flower induction.

PMID- 12232108
TI  - Nucleotide Availability in Maize (Zea mays L.) Root Tips (Estimation of Free and
      Protein-Bound Nucleotides Using 31P-Nuclear Magnetic Resonance and a Novel
      Protein-Ligand-Binding Assay).
AB  - Sequestration of nucleotides in cells through protein binding could influence the
      availability of nucleotides and free energy for metabolic reactions and,
      therefore, affect rates of physiological processes. We have estimated the
      proportion of nucleotides bound to proteins in maize (Zea mays L.) root tips.
      Binding of nucleoside mono- and diphosphates to total root-tip protein was
      studied in vitro using high-performance liquid chromatography and a new ligand
      binding technique. We estimate that approximately 40% of the ADP, 65% of the GDP,
      50% of the AMP, and virtually all the GMP in aerobic cells are bound to proteins.
      In hypoxic cells, free concentrations of these nucleotides increase
      proportionately much more than total intracellular concentrations. Little or no
      binding of CDP, UDP, CMP, and UMP was observed in vitro. Binding of nucleoside
      triphosphate (NTP) to protein was estimated from in vivo 31P-nuclear magnetic
      resonance relaxation measurements. In aerobic root tips most (approximately 70%)
      of the NTP is free, whereas under hypoxia NTP appears predominantly bound to
      protein. Our results indicate that binding of nucleotides to proteins in plant
      cells will significantly influence levels of free purine nucleotides available to
      drive and regulate respiration, protein synthesis, ion transport, and other
      physiological processes.

PMID- 12232109
TI  - Purification and Kinetic Properties of Serine Acetyltransferase Free of O
      Acetylserine(thiol)lyase from Spinach Chloroplasts.
AB  - Serine acetyltransferase, a key enzyme in the L-cysteine biosynthetic pathway,
      was purified over 300,000-fold from the stroma of spinach (Spinacia oleracea)
      leaf chloroplasts. The purification procedure consisted of ammonium sulfate
      precipitation, anion-exchange chromatography (Trisacryl M DEAE and Mono Q
      HR10/10), hydroxylapatite chromatography, and gel filtration (Superdex 200). The
      purified enzyme exhibited a specific activity higher than 200 units mg-1 and a
      subunit molecular mass of about 33 kD upon polyacrylamide gel electrophoresis in
      the presence of sodium dodecyl sulfate. Moreover, the purified serine
      acetyltransferase appeared to be essentially free of O-acetyleserine(thiol)lyase,
      another enzyme component in the L-cysteine biosynthetic pathway. A steady-state
      kinetic analysis indicated that the mechanism of the enzyme-catalyzed reaction
      involves a double displacement. The apparent Km for the two substrates, L-serine
      and acetyl-coenzyme A, were 2.29 [plus or minus] 0.43 and 0.35 [plus or minus]
      0.02 mM, respectively. The rate of L-cysteine synthesis in vitro was measured in
      a coupled enzyme assay using extensively purified O-acetylserine(thiol)lyase and
      serine acetyltransferase. This rate was maximum when the assay contained
      approximately a 400-fold excess of O-acetylserine(thiol)lyase over serine
      acetyltransferase. Measurements of the relative level of O
      acetylserine(thiol)lyase and serine acetyltransferase activities in the stroma
      indicated that the former enzyme was present in much larger quantities than the
      latter. Thus, the activity ratio for these two enzymes [O
      acetylserine(thiol)lyase activity/serine acetyltransferase activity] measured in
      the stromal protein extract was 345. This strongly suggested that all the O
      acetylserine(thiol)lyase and serine acetyltransferase activities in the stroma
      are involved in bringing a full synthesis of L-cysteine in the chloroplast.

PMID- 12232110
TI  - A Mutant Isolated from the Cyanobacterium Synechococcus PCC7942 Is Unable to
      Adapt to Low Inorganic Carbon Conditions.
AB  - Using a novel screening procedure, we have selected a new class of mutant from
      the cyanobacterium Synechococcus PCC7942 that fails to adapt to growth at an
      extremely low inorganic carbon (Ci) concentration. The mutant (Tm17) reported in
      this study grows normally at or above air levels of CO2 (340 [mu]L L-1) but does
      not survive at 20 [mu]L L-1 CO2 in air. Air-grown Tm17 cells showed properties
      similar to wild-type cells in various aspects of the CO2-concentrating mechanism
      examined. Following transfer from air levels to 20 [mu]L L-1 CO2, however, the
      mutant cells failed to increase their photosynthetic affinity for Ci. This
      results in an approximately 10-fold difference in photosynthetic affinity between
      the wild-type and Tm17 cells under Ci-limiting conditions [the K0.5(Ci) values
      were 11 and 136 [mu]M, respectively]. Further examination of factors possibly
      contributing to this low photosynthetic affinity showed that Tm17 cells have no
      inducible high-affinity HCO3- transport and do not appear to show induction of
      increased carboxysomal carbonic anhydrase and ribulose-1,5-bisphosphate
      carboxylase/oxygenase activities. It appears that a common factor, possibly
      relating to CO2 detection and/or induction signal, or the HCO3-transport
      mechanism may have been impaired in the mutant. Complementation results indicate
      that the mutation responsible for the phenotype has occurred in an 8- to 10-kb
      EcoRI genomic DNA fragment.

PMID- 12232111
TI  - Oligomerization and the Affinity of Maize Phosphoenolpyruvate Carboxylase for Its
      Substrate.
AB  - When two different forms of phosphoenolpyruvate carboxylase (PEPC) from maize
      (Zea mays L.) leaves are present in an assay it is possible to estimate the ratio
      of Vmax to Km (V/K) for the two forms separately. This measure of the binding of
      the substrate by the enzyme permits evaluation of the effects of various
      treatments on the relative substrate-binding velocity of the enzyme. PEPC diluted
      1/20 is present in a mixture of a tetrameric form with a high affinity for
      phosphoenolpyruvate and a dimeric form with a low affinity (M.-X. Wu, C.R. Meyer,
      K.O. Willeford, R.T. Wedding [1990] Arch Biochem Biophys 281: 324-329). Malate at
      5 mM reduced (V/K)1,[mdash]the V/K of the probable tetrameric form[mdash]almost
      to zero, but reduced (V/K)2[mdash]the V/K of the probable dimer[mdash]by only
      about 80%. Glucose-6-phosphate (Glc-6-P) at 5 mM increased (V/K)1 to 155% of the
      control but had no effect on (V/K)2. Glycerol (20%) alone increased both V/Ks,
      and its effects are additive to the Glc-6-P effects, implying different
      mechanisms for activation by Glc-6-P and glycerol.

PMID- 12232112
TI  - Inhibition of Apoplastic and Symplastic Peroxidase Activity from Norway Spruce by
      the Photooxidant Hydroxymethyl Hydroperoxide.
AB  - Young, clonal Norway spruce trees (Picea abies L.) were exposed for 2 years at
      high altitudes to ambient atmospheric concentrations of photooxidants containing
      hydroxymethyl hydroperoxide (HMHP) as an important constituent. In spruce needles
      from a site with higher concentrations of organic peroxides in air, the
      apoplastic peroxidase activities were significantly lower than in needles exposed
      to lower organic peroxide concentrations. Guaiacol peroxidase activities in total
      needle extracts were not affected. In vitro HMHP at a concentration of 35 [mu]M
      inhibited apoplastic and total needle guaiacol peroxidase activities by 50% at pH
      5.25. At the same pH, ascorbate-specific peroxidase activity required about 100
      [mu]M HMHP for 50% inhibition. At pH 7, 1.46 mM HMHP caused a 50% reduction in
      guaiacol peroxidase and a 13% reduction in ascorbate peroxidase activity. The
      present results suggest that HMHP in ambient air may affect peroxidase activity
      in spruce needles. Peroxidases located in the relatively acidic aqueous phase of
      the cell walls appear to be more susceptible to HMHP inhibition than those
      present in neutral or slightly alkaline symplastic compartments of cells such as
      the cytosol or chloroplasts.

PMID- 12232113
TI  - Cell-Wall Autohydrolysis in Isolated Endosperms of Lettuce (Lactuca sativa L.).
AB  - Cell walls prepared from the endosperm tissue of hydrated lettuce (Lactuca sativa
      L.) seeds undergo autohydrolysis. Release of carbohydrates is most rapid (0.4-0.6
      [mu]g per endosperm) within the 1st h of incubation in buffer, but substantial
      autolysis is sustained for at least 10 h. Autolysis is temperature sensitive, and
      the optimum rate occurs at pH 5. The rate of autolysis increases markedly in the
      period just prior to radicle emergence. The cell-wall polysaccharide composition
      in micropylar and lateral endosperm regions differs significantly; the micropylar
      walls are rich in arabinose and glucose with substantially lower amounts of
      mannose. Although walls prepared from both micropylar and lateral regions undergo
      autolysis, micropylar walls release carbohydrates at a higher rate than lateral
      walls. Autolysis products elute as large polymers when subjected to size
      exclusion chromatography, suggesting that endo-enzyme activity is responsible for
      release of fragments containing arabinose, galactose, mannose, and uronic acids.
      Arabinose, galactose, mannose, and glucose are also released as monomers. As a
      function of time, the ratio of polymers to monomers decreases, indicating that
      exo-enzyme activity is also present. Thermoinhibition or treatment with abscisic
      acid suppresses germination and reduces the rates of autolysis of walls isolated
      from the endosperm by about 25%. Treatments that alleviate thermoinhibition
      (kinetin and gibberellic acid) increase the rates of autolysis by 20 to 30% when
      compared to thermoinhibited controls.

PMID- 12232114
TI  - Inorganic Phosphate (Pi) Enhancement of Dark Respiration in the Pi-Limited Green
      Alga Selenastrum minutum (Interactions between H+/Pi Cotransport, the Plasmalemma
      H+-ATPase, and Dark Respiratory Carbon Flow).
AB  - Inorganic phosphate (Pi) enrichment of the Pi-limited green alga Selenastrum
      minutum in the dark caused a 2.5-fold increase in the rate of O2 consumption.
      Alkalization of the media during Pi assimilation was consistent with a H+/Pi
      cotransport mechanism with a stoichiometry of at least 2 H+ cotransported per Pi.
      Dark O2 consumption remained enhanced beyond the period of Pi assimilation and
      did not recover until the medium was reacidified. This result, coupled with an
      immediate decrease in adenylate energy charge following Pi enrichment, suggested
      that respiration is regulated by the ATP requirements of a plasmalemma H+-ATPase
      that is activated to maintain intracellular pH and provide proton motive force to
      power Pi uptake. Concentrations of tricarboxylic acid cycle intermediates
      decreased following Pi enrichment and respiratory CO2 efflux increased,
      indicating that the tricarboxylic acid cycle was activated to supply reductant to
      the mitochondrial electron transport chain. These results are consistent with
      direct inhibition of electron transport by ADP limitation. Enhanced rates of
      starch breakdown and increases in glycolytic metabolites indicated that
      respiratory carbon flow was activated to supply reductant to the electron
      transport chain and to rapidly assimilate Pi into metabolic intermediates. The
      mechanism that initiates glycolytic carbon flow could not be clearly identified
      by product:substrate ratios due to the complex nature of Pi assimilation. High
      levels of triose-P and low levels of phosphoenolpyruvate were the primary
      regulators of pyruvate kinase and phosphofructokinase, respectively.

PMID- 12232115
TI  - Iron Transport to Developing Ovules of Pisum sativum (I. Seed Import
      Characteristics and Phloem Iron-Loading Capacity of Source Regions).
AB  - To understand the processes that control Fe transport to developing seeds, we
      have characterized seed growth and Fe accretion and have developed a radiotracer
      technique for quantifying phloem Fe loading in vegetative source regions of Pisum
      sativum. In hydroponically grown plants of cv Sparkle, developing ovules
      exhibited a seed-growth period of 22 d, with Fe import occurring throughout the
      22-d period. Average Fe content of mature seeds was 19 [mu]g. Source tissues of
      intact plants were abraded and pulse labeled for 4 h with 100 [mu]M 59Fe(III)
      citrate. Fe was successfully phloem loaded and transported to seeds from
      leaflets, stipules, and pod walls. Total export of 59Fe from labeled source
      regions was used to calculate tissue-loading rates of 36, 40, and 51 pmol of Fe
      cm-2 h-1 for the leaflet, stipule, and pod wall surfaces, respectively. By
      comparison, surface area measurements, along with seed-growth results, allowed us
      to calculate average theoretical influx values of 42 or 68 pmol of Fe cm-2 h-1
      for vegetative tissues at nodes with one or two pods, respectively. Additional
      studies with the regulatory pea mutant, E107 (a single-gene mutant of cv Sparkle
      that can overaccumulate Fe), enabled us to increase Fe delivery endogenously to
      the vegetative tissues. A 36-fold increase in Fe content of E107 leaves, relative
      to Sparkle, resulted in no increase in Fe content of E107 seeds. Based on these
      findings, we hypothesized that Fe is phloem loaded in a chelated form, and the
      expression/synthesis of the endogenous chelator is an important factor in the
      control of Fe transport to the seeds.

PMID- 12232116
TI  - Phosphorus Stress-Induced Proteoid Roots Show Altered Metabolism in Lupinus
      albus.
AB  - Proteoid roots develop in Lupinus albus L. in response to nutrient stress,
      especially P. Proteoid roots excrete citrate and thus increase the availability
      of P, Fe, and Mn in the rhizosphere. In an effort to understand citrate synthesis
      and organic acid metabolism in proteoid roots of lupin, we have evaluated in
      vitro enzyme activities of citrate synthase (CS), malate dehydrogenase (MDH), and
      phosphoenolpyruvate carboxylase (PEPC) in proteoid and normal roots of plants
      grown with or without P. Organic acid concentrations, respiration rates, and dark
      14CO2-labeling patterns were also determined. The in vitro specific activities of
      CS, MDH, and PEPC and in vivo dark 14CO2 fixation were higher in proteoid roots
      compared to normal roots, particularly under P stress. Western blot analysis
      showed that PEPC enzyme protein was more highly expressed in -P proteoid roots
      compared to other tissues. The majority of the fixed 14C was found in organic
      acids, predominantly malate and citrate. A larger fraction of citrate was labeled
      in P- stressed proteoid roots compared to other root tissue. Respiration rates of
      proteoid roots were 31% less than those of normal roots. The data provide
      evidence for increased synthesis of citrate in proteoid roots compared to normal
      roots, particularly under P stress. A portion of the carbon for citrate synthesis
      is derived from nonautotrophic CO2 fixation via PEPC in proteoid roots.

PMID- 12232117
TI  - Chlorophyll Fluorescence as a Possible Tool for Salinity Tolerance Screening in
      Barley (Hordeum vulgare L.).
AB  - The application of chlorophyll fluorescence measurements to screening barley
      (Hordeum vulgare L.) genotypes for salinity tolerance has been investigated.
      Excised barley leaves were cut under water and incubated with the cut end
      immersed in water or in a 100-mM NaCl solution, either in the dark or in high
      light. Changes in rapid fluorescence kinetics occurred in excised barley leaves
      exposed to the saline solution only when the incubation was carried out in the
      presence of high light. Fluorescence changes consisted of decreases in the
      variable to maximum fluorescence ratio and in increases in the relative
      proportion of variable fluorescence leading to point I in the Kautsky
      fluorescence induction curve. These relative increases in fluorescence at point I
      appeared to arise from a delayed plastoquinone reoxidation in the dark, since
      they disappeared after short, far-red illumination, which is known to excite
      photosystem I preferentially. We show that a significant correlation existed
      between some fluorescence parameters, measured after a combined salt and high
      light treatment, and other independent measurements of salinity tolerance. These
      results suggest that chlorophyll fluorescence, and especially the relative
      fluorescence at point I in the Kautsky fluorescence induction curve, could be
      used for the screening of barley genotypes for salinity tolerance.

PMID- 12232118
TI  - Water Relations and Low-Temperature Acclimation for Cactus Species Varying in
      Freezing Tolerance.
AB  - Opuntia ficus-indica and Opuntia streptacantha are widely cultivated cacti that
      can tolerate temperatures no lower than -10[deg]C, whereas Opuntia humifusa,
      which is native to southern Canada and the eastern United States, can tolerate 
      24[deg]C. As day/night air temperatures were decreased from 30/20 to 10/0[deg]C,
      the osmotic pressure increased 0.10 MPa for O. ficus-indica and O. streptacantha
      but 0.38 MPa for O. humifusa. The increases in osmotic pressures were due mostly
      to the synthesis of fructose, glucose, and sucrose. In addition, O. humifusa
      produced a substantial amount of mannitol during exposure to low temperatures.
      Substantial accumulation of sugars and mannitol in cells of O. humifusa may help
      prevent intracellular freeze dehydration and ice formation as well as provide
      noncolligative protection to its membranes. Mucilage was slightly higher in all
      three species at the lower temperatures. Extracellular nucleation of ice occurred
      closer to the equilibrium freezing temperature for plants at 10/0[deg]C compared
      with 30/20[deg]C, which could make the cellular dehydration more gradual and,
      thus, less damaging. Results from nuclear magnetic resonance indicated a
      restricted mobility of intracellular water at the lower temperatures, especially
      for O. humifusa, which is consistent with its lower water content and higher
      levels of low molecular weight solutes.

PMID- 12232119
TI  - A Vesicular Arbuscular Mycorrhizal Fungus (Glomus intraradix) Induces a Defense
      Response in Alfalfa Roots.
AB  - Flavonoid accumulation and activities of phenylalanine ammonia-lyase (PAL),
      chalcone isomerase (CHI), and chitinase were followed during early colonization
      of alfalfa roots (Medicago sativa L. cv Gilboa) by vesicular arbuscular (VA)
      fungi (Glomus intraradix). Formononetin was the only flavonoid detected that
      showed a consistent increase in the inoculated roots. This increase depended only
      on the presence of the fungus in the plant rhizosphere; no colonization of the
      root tissue was required. CHI and chitinase activities increased in inoculated
      roots prior to colonization, whereas the increase in PAL activity coincided with
      colonization. After reaching a maximum, activities of all enzymes declined to
      below those of uninoculated roots. PAL inactivation was not caused by a soluble
      inhibitor. Our results indicate that VA fungi initiate a host defense response in
      alfalfa roots, which is subsequently suppressed.

PMID- 12232120
TI  - Modulation of Fusicoccin-Binding Protein Activity in Mung Bean (Vigna radiata L.)
      Hypocotyls by Tissue Maturation and by Fusicoccin.
AB  - The phytotoxin fusicoccin (FC), after binding to a plasma membrane-localized
      receptor, causes higher plant cells to excrete protons. Ligand-binding analysis
      has been used to show that the plasma membrane of mung bean (Vigna radiata L.)
      hypocotyls contains both high-affinity (HA) and low-affinity (LA) binding sites
      for FC. The effect of tissue maturation on these sites was determined on isolated
      membrane vesicles from the meristematic region (hook) and the elongation zone and
      from mature hypocotyl tissues. In the meristematic region the HA:LA ratio was
      1:20. As hypocotyl tissues matured, the site density of HA increased and there
      was no change in LA density, so that the HA:LA ratio increased to 1:2 in maturet
      issues. FC-induced proton excretion correlates with the HA density, not the LA
      density. When sections isolated from each region were incubated with FC prior to
      isolation of membranes, there was an apparent conversion of LA to HA sites during
      the first 90 min in all regions. During the next 1 to 3 h there was a further 2.5
      to 3- fold increase in binding sites in all regions, accompanied by a slight
      decline in dissociation constant. The increase in binding sites, but not the
      apparent conversion of LA to HA, was partly blocked by cycloheximide. These data
      suggest that FC alters FC-binding protein activity in two ways: first, by causing
      an increase in affinity for FC of preexisting LA receptors, and second by
      inducing the synthesis of additional FC receptors. This apparent up-regulation of
      a phytotoxin receptor by its ligand in plants has not previously been reported.

PMID- 12232121
TI  - Cuticle Biosynthesis in Rapidly Growing Internodes of Deepwater Rice.
AB  - Submergence induces rapid elongation of deepwater rice (Oryza sativa L.)
      internodes. This adaptive feature allows deepwater rice to grow out of the water
      and to survive flooding. The growth response of submerged deepwater rice plants
      is, ultimately, elicited by gibberellin (GA). Little attention has been given to
      the synthesis and role of the cuticle during plant growth. We investigated two
      questions regarding the cuticle in rapidly elongating deepwater rice internodes:
      (a) how does cuticle formation keep pace with internodal growth, which can reach
      rates of up to 5 mm/h; and (b) does the cuticle contribute to tissue stress in
      rice internodes? Treatment with GA for 48 h caused an up to 60-fold increase in
      the incorporation of [14C]palmitic acid and an up to 6-fold increase in the
      incorporation of [14C]oleic acid into the cuticle of growing internodes. GA also
      caused a qualitative change in the incorporation pattern of palmitic acid into
      several cutin monomers, the most prominent of which was tentatively identified by
      thin-layer chromatography as a derivative of dihydroxyhexadecanoic acid. Rapidly
      growing plant organs exhibit longitudinal tissue stress: the epidermal cell layer
      is under tension with a tendency to contract, whereas the internal cells are
      under compression with a tendency to expand. As a result of tissue stress,
      longitudinally sliced sections of elongating internodes bend outward upon
      isolation from the plant. Treating rapidly growing rice internodes with cutinase
      reduced such outward bending, indicating that the cuticle contributes to tissue
      stress. Based on these results, we propose that rapidly elongating structures
      such as deepwater rice internodes constitute an excellent system to study cuticle
      formation at the biochemical and cellular level.

PMID- 12232122
TI  - Characterization and Quantification of Intrinsic Ice Nucleators in Winter Rye
      (Secale cereale) Leaves.
AB  - Extracellular ice formation in frost-tolerant organisms is often initiated at
      specific sites by ice nucleators. In this study, we examined ice nucleation
      activity (INA) in the frost-tolerant plant winter rye (Secale cereale). Plants
      were grown at 20[deg]C, at 5[deg]C with a long day, and at 5[deg]C with a short
      day (5[deg]C-SD). The threshold temperature for INA was -5 to -12[deg]C in winter
      rye leaves from all three growth treatments. Epiphytic ice nucleation-active
      bacteria could not account for INA observed in the leaves. Therefore, the INA
      must have been produced endogenously. Intrinsic rye ice nucleators were
      quantified and characterized using single mesophyll cell suspensions obtained by
      pectolytic degradation of the leaves. The most active ice nucleators in mesophyll
      cell suspensions exhibited a threshold ice nucleation temperature of -7[deg]C and
      occurred infrequently at the rate of one nucleator per 105 cells. Rye cells were
      treated with chemicals and enzymes to characterize the ice nucleators, which
      proved to be complexes of proteins, carbohydrates, and phospholipids, in which
      both disulfide bonds and free sulfhydryl groups were important for activity.
      Carbohydrates and phospholipids were important components of ice nucleators
      derived from 20[deg]C leaves, whereas the protein component was more important in
      5[deg]C-SD leaves. This difference in composition or structure of the ice
      nucleators, combined with a tendency for more frequent INA, suggests that more
      ice nucleators are produced in 5[deg]C-SD leaves. These additional ice nucleators
      may be a component of the mechanism for freezing tolerance observed in winter
      rye.

PMID- 12232123
TI  - Response of Xylem Ray Parenchyma Cells of Red Osier Dogwood (Cornus sericea L.)
      to Freezing Stress (Microscopic Evidence of Protoplasm Contraction).
AB  - Freezing behavior of wood tissue of red osier dogwood (Cornus sericea L.) cannot
      be explained by current concepts of freezing resistance. Previous studies
      indicated that water in wood tissue presumably froze extracellularly. However, it
      was observed that xylem ray parenchyma cells within these tissues could survive
      temperatures as low as -80[deg]C and the walls of these cells did not collapse
      during freezing (S.R. Malone and E.N. Ashworth [1991] Plant Physiol 95: 871-881).
      This observation was unexpected and is inconsistent with the current hypothesis
      of cell response during freezing. Hence, the objective of our study was to
      further examine the mechanism of freezing resistance of wood tissue of red osier
      dogwood. We studied freezing stress response of xylem ray parenchyma cells of red
      osier dogwood using freeze substitution and transmission electron microscopy.
      Wood samples were collected in winter, spring, and summer of 1992. Specimens were
      cooled from 0[deg]C to -60[deg]C at 5[deg]C/h. Freezing stress did not affect the
      structural organization of wood tissue. However, the xylem ray parenchyma cells
      showed two unique responses to a freezing stress: protoplasm contraction and
      protoplasm fragmentation. Protoplasm contraction was evident at all freezing
      temperatures and in tissues collected at different times of the year. Cells with
      fragmented protoplasm, however, were noticed only in tissues collected in spring
      and summer. Protoplasm contraction in winter tissue occurred without apparent
      damage to the protoplasm. In contrast, protoplasm contraction in spring and
      summer tissues was accompanied by substantial damage. No evidence of
      intracellular ice formation was observed in parenchyma cells exposed to freezing
      stress. Differences in protoplasm contraction and appearance of cells with
      fragmented protoplasm likely indicated seasonal changes in cold hardiness of the
      wood tissue of red osier dogwood. We speculate that the appearance of fragmented
      protoplasm may indicate that cells are being injured by an alternative mechanism
      in spring and summer.

PMID- 12232124
TI  - Drought Rhizogenesis in Arabidopsis thaliana (Differential Responses of Hormonal
      Mutants).
AB  - Drought rhizogenesis is an adaptive strategy that occurs during progressive
      drought stress and is characterized in the Brassicaceae and related families by
      the formation of short, tuberized, hairless roots. These roots are capable of
      withstanding a prolonged drought period and give rise to a new functional root
      system upon rehydration. The kinetics of drought rhizogenesis during progressive
      water shortage was analyzed in the Arabidopsis thaliana wild-type ecotypes
      Landsberg erecta and Columbia. In both genotypes, this response started from a
      similar threshold of soil humidity (about 2%). The intensity of drought
      rhizogenesis was compared in various A. thaliana hormonal mutants. The wild-type
      lines and most of the mutants achieved a similiar drought rhizogenetic index
      (DRI), defined as the maximum number of short roots produced per mg of root
      biomass, after progressive drought stress. However, this DRI was dramatically
      reduced in the abscisic acid (ABA)-deficient aba, ABA-insensitive abi1-1, and
      auxin-resistant axr1-3 mutants. These data indicate that endogenous ABA and auxin
      play a promotive role in drought rhizogenesis. The DRI was highly increased in
      the gibberellin (GA) biosynthetic mutant ga5, suggesting that some GAs might also
      participate in this process. The possible role and identity of the GA species
      involved is discussed in view of the unaltered DRI values of the ga2, ga3, and
      ga4 mutants. The present analysis also allowed further discrimination among the
      various ABA-insensitive (abi1 versus abi2 and abi3) and auxin-resistant (axr1
      versus aux1) mutants tested. In particular, drought rhizogenesis is the first
      physiological response shown to be differentially affected by the abi1-1 and abi2
      1 mutations.

PMID- 12232125
TI  - Mutants of Chloroplast Coupling Factor Reduction in Arabidopsis.
AB  - We have devised a two-step screening strategy for the selection of chloroplast
      coupling factor reduction mutants from an M2 population of Arabidopsis thaliana.
      The selection strategy relies on a lowered energetic threshold for catalytic
      activation of the enzyme that has been shown to accompany thioredoxin-mediated
      reduction of a cysteine bridge on the [gamma] subunit of coupling factor. We
      selected first for plants that grew poorly under low irradiance but performed
      satisfactorily at high irradiance when the transmembrane electrochemical
      potential of hydrogen ions is large and competent to maintain a high level of
      coupling factor activation without [gamma] subunit reduction. In the second step
      of the screen we monitored the flash-induced electrochromic change to select
      putative coupling factor reduction mutants from other sorts of mutations that
      shared the phenotype of poor growth and vigor when transferred from high to low
      irradiance. Among the mutants selected, one appears incapable of reducing
      coupling factor, whereas another behaves as though coupling factor is at least
      partially reduced even in dark-adapted plants.

PMID- 12232126
TI  - Quenching of Chlorophyll a Fluorescence in Response to Na+-Dependent HCO3-
      Transport-Mediated Accumulation of Inorganic Carbon in the Cyanobacterium
      Synechococcus UTEX 625.
AB  - In the cyanobacterium Synechococcus UTEX 625, the yield of chlorophyll a
      fluorescence decreased in response to the transport-mediated accumulation of
      intracellular inorganic carbon (CO2 + HCO3- + CO32- = dissolved inorganic carbon
      [DIC]) and subsequently increased to a near-maximum level following
      photosynthetic depletion of the DIC pool. When DIC accumulation was mediated by
      the active Na+-dependent HCO3- transport system, the initial rate of fluorescence
      quenching was found to be highly correlated with the initial rate of H14CO3-
      transport (r = 0.96), and the extent of fluorescence quenching was correlated
      with the size of the internal DIC pool (r = 0.99). Na+-dependent HCO3- transport
      mediated accumulation of DIC caused fluorescence quenching in either the presence
      or absence of the CO2 fixation inhibitor glycolaldehyde, indicating that
      quenching was not due simply to NADP+ reduction. The concentration of Na+
      required to attain one-half the maximum rate of H14CO3- transport, at 20 [mu]M
      external HCO3-, declined from 9 to 1 mM as the external pH increased from 8 to
      9.6. A similar pH dependency was observed when fluorescence quenching was used to
      determine the kinetic constants for HCO3- transport. In cells capable of Na+
      dependent HCO3- transport, both the initial rate and extent of fluorescence
      quenching increased with increasing external HCO3-, saturating at about 150
      [mu]M. In contrast Na+-independent HCO3- transport-mediated fluorescence
      quenching saturated at an HCO3- concentration of about 10 [mu]M. It was concluded
      that measurement of chlorophyll a fluorescence emission provided a convenient,
      but indirect, means of following Na+-dependent HCO3- transport and accumulation
      in Synechococcus.

PMID- 12232127
TI  - Iron: Nutritious, Noxious, and Not Readily Available.

PMID- 12232128
TI  - Design of New Plant Products: Engineering of Fatty Acid Metabolism.

PMID- 12232129
TI  - Metabolic Evidence for the Involvement of a [delta]4-Palmitoyl-Acyl Carrier
      Protein Desaturase in Petroselinic Acid Synthesis in Coriander Endosperm and
      Transgenic Tobacco Cells.
AB  - We have previously demonstrated that the double bond of petroselinic acid
      (18:1[delta]6cis) in coriander (Coriandrum sativum L.) seed results from the
      activity of a 36-kD desaturase that is structurally related to the [delta]9
      stearoyl-acyl carrier protein (ACP) desaturase (E.B. Cahoon, J. Shanklin, J.B.
      Ohlrogge [1992] Proc Natl Acad Sci USA 89: 11184-11188). To further characterize
      the biosynthetic pathway of this unusual fatty acid, 14C-labeling experiments
      were conducted using developing endosperm of coriander. Studies were also
      performed using suspension cultures of transgenic tobacco (Nicotiana tabacum L.)
      that express the coriander 36-kD desaturase, and as a result produce petroselinic
      acid and [delta]4-hexadecenoic acid. When supplied exogenously to coriander
      endosperm slices, [1-14C]palmitic acid and stearic acid were incorporated into
      glycerolipids but were not converted to petroselinic acid. This suggested that
      petroselinic acid is not formed by the desaturation of a fatty acid bound to a
      glycerolipid or by reactions involving acyl-coenzyme As (CoA). Instead, evidence
      was most consistent with an acyl-ACP route of petroselinic acid synthesis. For
      example, the exogenous feeding of [1-14C]lauric acid and myristic acid to
      coriander endosperm slices resulted in the incorporation of the radiolabels into
      long-chain fatty acids, including primarily petroselinic acid, presumably through
      acyl-ACP-associated reactions. In addition, using an in vitro fatty acid
      biosynthetic system, homogenates of coriander endosperm incorporated [2
      14C]malonyl-CoA into petroselinic acid, of which a portion was detected in a
      putative acyl-ACP fraction. Furthermore, analysis of transgenic tobacco
      suspension cultures expressing the coriander 36-kD desaturase revealed
      significant amounts of petroselinic acid and [delta]4-hexadecenoic acid in the
      acyl-ACP pool of these cells. Also presented is evidence derived from [U
      14C]nonanoic acid labeling of coriander endosperm, which demonstrates that the
      coriander 36-kD desaturase positions double bonds relative to the carboxyl end of
      acyl-ACP substrates. The data obtained in these studies are rationalized in terms
      of a biosynthetic pathway of petroselinic acid involving the [delta]4
      desaturation of palmitoyl-ACP by the 36-kD desaturase followed by two-carbon
      elongation of the resulting [delta]4-hexadecenoyl-ACP.

PMID- 12232130
TI  - Specificities of the Acyl-Acyl Carrier Protein (ACP) Thioesterase and Glycerol-3
      Phosphate Acyltransferase for Octadecenoyl-ACP Isomers (Identification of a
      Petroselinoyl-ACP Thioesterase in Umbelliferae).
AB  - This study was designed to address the question: How specific for double bond
      position and conformation are plant enzymes that act on oleoyl-acyl carrier
      protein (ACP)? Octadecenoyl-ACPs with cis double bonds at positions [delta]6,
      [delta]7, [delta]8, [delta]9, [delta]10, [delta]11, or [delta]12 and elaidyl
      (18:1[delta]9trans)-ACP were synthesized and used to characterize the substrate
      specificity of the acyl-ACP thioesterase and acyl-ACP:sn-glycerol-3-phosphate
      acyltransferase. The two enzymes were found to be specific for the [delta]9
      position of the double bond. The thioesterase was highly specific for the
      [delta]9 cis conformation, but the transferase was almost equally active with the
      cis and the trans isomer of 18:1[delta]9-ACP. In plants such as the Umbelliferae
      species coriander (Coriandrum sativum L.) that accumulate petroselinic acid
      (18:1[delta]6cis) in their seed triacylglycerols, a high petroselinoyl-ACP
      thioesterase activity was found in addition to the oleoyl-ACP thioesterase. The
      two activities could be separated by anion-exchange chromatography, indicating
      that the petroselinoyl-ACP thioesterase is represented by a distinct polypeptide.

PMID- 12232131
TI  - Apparent Role of Phosphatidylcholine in the Metabolism of Petroselinic Acid in
      Developing Umbelliferae Endosperm.
AB  - Studies were conducted to characterize the metabolism of the unusual fatty acid
      petroselinic acid (18:1cis[delta]6) in developing endosperm of the Umbelliferae
      species coriander (Coriandrum sativum L.) and carrot (Daucus carota L.). Analyses
      of fatty acid compositions of glycerolipids of these tissues revealed a
      dissimilar distribution of petroselinic acid in triacylglycerols (TAG) and the
      major polar lipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE).
      Petroselinic acid comprised 70 to 75 mol% of the fatty acids of TAG but only 9 to
      20 mol% of the fatty acids of PC and PE. Although such data appeared to suggest
      that petroselinic acid is at least partially excluded from polar lipids, results
      of [1-14C]acetate radiolabeling experiments gave a much different picture of the
      metabolism of this fatty acid. In time-course labeling of carrot endosperm, [1
      14C]acetate was rapidly incorporated into PC in high levels. Through 30 min,
      radiolabel was most concentrated in PC, and of this, 80 to 85% was in the form of
      petroselinic acid. One explanation for the large disparity in amounts of
      petroselinic acid in PC as determined by fatty acid mass analyses and 14C
      radiolabeling is that turnover of these lipids or the fatty acids of these lipids
      results in relatively low accumulation of petroselinic acid mass. Consistent with
      this, the kinetics of [1-14C]acetate time-course labeling of carrot endosperm and
      "pulse-chase" labeling of coriander endosperm suggested a possible flux of fatty
      acids from PC into TAG. In time-course experiments, radiolabel initially entered
      PC at the highest rates but accumulated in TAG at later time points. Similarly,
      in pulse-chase studies, losses in absolute amounts of radioactivity from PC were
      accompanied by significant increases of radiolabel in TAG. In addition,
      stereospecific analyses of unlabeled and [1-14C]acetate-labeled PC of coriander
      endosperm indicated that petroselinic acid can be readily incorporated into both
      the sn-1 and sn-2 positions of this lipid. Because petroselinic acid is neither
      synthesized nor further modified on polar lipids, the apparent metabolism of this
      fatty acid through PC (and possibly through other polar lipids) may define a
      function of PC in TAG assembly apart from its involvement in fatty acid
      modification reactions.

PMID- 12232132
TI  - The Synthesis of [gamma]-Aminobutyric Acid in Response to Treatments Reducing
      Cytosolic pH.
AB  - [gamma]-Aminobutyric acid (GABA) synthesis (L-glutamic acid + H+ -> GABA + CO2)
      is rapidly stimulated by a variety of stress conditions including hypoxia. Recent
      literature suggests that GABA production and concomitant H+ consumption
      ameliorates the cytosolic acidification associated with hypoxia or other
      stresses. This proposal was investigated using isolated asparagus (Asparagus
      sprengeri Regel) mesophyll cells. Cell acidification was promoted using hypoxia,
      H+/L-glutamic acid symport, and addition of butyrate or other permeant weak
      acids. Sixty minutes of all three treatments stimulated the levels of both
      intracellular and extracellular GABA by values ranging from 100 to 1800%. At an
      external pH of 5.0, addition of 5 mM butyrate stimulated an increase in overall
      GABA level from 3.86 (0.56 [plus or minus] SE) to 20.4 (2.16 [plus or minus] SE)
      nmol of GABA/106 cell. Butyrate stimulated GABA levels by 200 to 300% within 15
      s, and extracellular GABA was observed after 10 min. The acid load due to
      butyrate addition was assayed by measuring [14C]butyrate uptake. After 45 s of
      butyrate treatment, H+-consuming GABA production accounted for 45% of the imposed
      acid load. The cytosolic location of a fluorescent pH probe was confirmed using
      fluorescent microscopy. Spectrofluorimetry indicated that butyrate addition
      reduced cytosolic pH by 0.60 units with a half-time of approximately 2 s. The
      proposal that GABA synthesis ameliorates cytosolic acidification is supported by
      the data. The possible roles of H+ and Ca2+ in stimulating GABA synthesis are
      discussed.

PMID- 12232133
TI  - Isolation of an Arabidopsis thaliana Mutant, mto1, That Overaccumulates Soluble
      Methionine (Temporal and Spatial Patterns of Soluble Methionine Accumulation).
AB  - We isolated Arabidopsis thaliana mutants that are resistant to ethionine, a toxic
      analog of methionine (Met). One of the mutants was analyzed further, and it
      accumulated 10- to 40-fold more soluble Met than the wild type in the aerial
      parts during the vegetative growth period. When the mutant plants started to
      flower, however, the soluble Met content in the rosette region decreased to the
      wild-type level, whereas that in the inflorescence apex region and in immature
      fruits was 5- to 8-fold higher than the wild type. These results indicate that
      the concentration of soluble Met is temporally and spatially regulated and
      suggest that soluble Met is translocated to sink organs after the onset of
      reproductive growth. The causal mutation, designated mto1, was a single, nuclear,
      semidominant mutation and mapped to chromosome 3. Accumulation profiles of
      soluble amino acids suggested that the mutation affects a later step(s) in the
      Met biosynthesis pathway. Ethylene production of the mutants was only 40% higher
      than the wild-type plants, indicating that ethylene production is tightly
      regulated at a step after Met synthesis. This mutant will be useful in studying
      the translocation of amino acids, as well as regulation of Met biosynthesis and
      other metabolic pathways related to Met.

PMID- 12232135
TI  - Ammonium Uptake by Rice Roots (III. Electrophysiology).
AB  - The transmembrane electrical potential differences ([delta][psi]) were measured
      in epidermal and cortical cells of intact roots of 3-week-old rice (Oryza sativa
      L. cv M202) seedlings grown in 2 or 100 [mu]M NH4+ (G2 or G100 plants,
      respectively). In modified Johnson's nutrient solution containing no nitrogen,
      [delta][psi] was in the range of -120 to -140 mV. Introducing NH4+ to the bathing
      medium caused a rapid depolarization. At the steady state, average [delta][psi]
      of G2 and G100 plants were -116 and -89 mV, respectively. This depolarization
      exhibited a biphasic response to external NH4+ concentration similar to that
      reported for 13NH4+ influx isotherms (M.Y. Wang, M.Y. Siddiqi, T.J. Ruth, A.D.M.
      Glass [1993] Plant Physiol 103: 1259-1267). Plots of membrane depolarization
      versus 13NH4+ influx were also biphasic, indicating distinct coupling processes
      for the two transport systems, with a breakpoint between two concentration ranges
      around 1 mM NH4+. The extent of depolarization was also influenced by nitrogen
      status, which was larger for G2 plants than for G100 plants. Depolarization of
      [delta][psi] due to NH4+ uptake was eliminated by a protonophore (carboxylcyanide
      m-chlorophenylhydrazone), inhibitors of ATP synthesis (sodium cyanide plus
      salicylhydroxamic acid), or an ATPase inhibitor (diethylstilbestrol). The results
      of these observations are discussed in the context of the mechanisms of NH4+
      uptake by high- and low-affinity transport systems operating across the plasma
      membranes of root cells.

PMID- 12232134
TI  - Interactions between Light and the Circadian Clock in the Regulation of CAT2
      Expression in Arabidopsis.
AB  - In Arabidopsis seedlings germinated and grown in continuous light, CAT2 mRNA
      abundance peaks 1 d after imbibition, consistent with the role of catalase in
      detoxifying H2O2 generated during the [beta]-oxidation of fatty acids stored in
      the seed. A second peak of CAT2 mRNA abundance, of lower amplitude than the
      initial peak, appears 6 d after imbibition and may be associated with the
      development of photosynthetic competence and induction of photorespiration. This
      second peak in steady-state CAT2 mRNA abundance is regulated by light and is not
      seen in etiolated seedlings. CAT2 mRNA accumulation is induced by exposure to
      high-fluence blue or far-red light but not by red light. In addition, light
      induction is unaffected by several mutations that block blue light-mediated
      inhibition of hypocotyl elongation (blu1, blu2, blu3, hy4), suggesting
      phytochrome involvement. When etiolated seedlings are transferred to continuous
      white light, CAT2 mRNA rapidly (within 30 min) accumulates. It is interesting
      that in these seedlings CAT2 mRNA abundance undergoes pronounced oscillations
      with a circadian (24 h) periodicity, indicating control by the endogenous
      circadian clock. No such oscillations are detected in CAT2 mRNA abundance in
      etiolated seedlings prior to illumination. Control of CAT2 expression by the
      circadian clock is also seen in 5-week-old plants grown in a light-dark cycle and
      transferred either to continuous dark or to continuous light; in continuous light
      the circadian oscillations in CAT2 mRNA abundance persist for at least five
      circadian cycles, indicating the robustness of this circadian rhythm.

PMID- 12232136
TI  - Cyclic [beta]-1,6-1,3-Glucans of Bradyrhizobium japonicum USDA 110 Elicit
      Isoflavonoid Production in the Soybean (Glycine max) Host.
AB  - High levels of cyclic [beta]-1,6-1,3-glucans (e.g. 0.1 mg mg-1 of total protein)
      are synthesized by free-living cells as well as by bacteroids of Bradyrhizobium
      japonicum USDA 110 (K.J. Miller, R.S. Gore, R. Johnson, A.J. Benesi, V.N.
      Reinhold [1990] J Bacteriol 172: 136-142; R.S. Gore and K.J. Miller [1993] Plant
      Physiol 102: 191-194). These molecules share structural features with glucan
      fragments isolated from the mycelial cell wall of the soybean (Glycine max)
      pathogen Phytophthora megasperma. These latter glucans have been shown to be
      potent elicitors (at nanogram levels) of the phytoalexin glyceollin in G. max.
      Using the well-characterized soybean cotyledon bioassay, we now show that the
      cyclic [beta]-1,6-1,3-glucans of B. japonicum USDA 110 are also biologically
      active elicitors of glyceollin production (but at microgram levels). We further
      show that both classes of [beta]-glucans elicit the production of the isoflavone
      daidzein within soybean cotyledon wound droplets.

PMID- 12232138
TI  - Changes in Soybean Fruit Ca2+ (Sr2+) and K+ (Rb+) Transport Ability during
      Development.
AB  - Mineral uptake by soybean (Glycine max [L.] Merrill) seeds during development can
      significantly affect seed quality and value. Little is known about seed mineral
      transport mechanisms and control processes, although it is clear that each
      mineral displays a characteristic accumulation pattern. Ion-specific accumulation
      patterns could result from changes in source availability, in transport kinetics
      through the seed pod and seed coat, or in the mineral uptake capability of the
      embryo. Ca2+ and K+ have negligible and high phloem mobilities, respectively.
      Ca2+ accumulation lags behind dry matter (C and N) and K+ accumulation in soybean
      embryos. To eliminate source availability influences, the Ca2+ and K+ uptake
      ability of isolated embryos and of seeds in pod culture was examined during seed
      development. Sr2+ and Rb+ were used as transport analogs of Ca2+ and K+,
      respectively. Sr2+ and Rb+ uptake rates by isolated embryos increased with seed
      fresh weight, indicating that the embryo was not limiting Ca2+ accumulation.
      However, the pod-cultured embryo Sr2+ and Rb+ uptake rate trends differed: Rb+
      uptake increased with seed fresh weight, whereas Sr2+ uptake rates remained
      constant or decreased slightly. Ovule Sr2+ influx data suggest that the pod and
      seed coat impose a transport barrier that could account for the relative decline
      in embryo Ca2+ content during development.

PMID- 12232139
TI  - Involvement of Oxidative Processes in the Signaling Mechanisms Leading to the
      Activation of Glyceollin Synthesis in Soybean (Glycine max).
AB  - The efficiency of hydroperoxides (tert-butyl hydroperoxide, hydrogen peroxide)
      and sulfhydryl reagents (iodoacetamide, p-chloromercuribenzene sulfonic acid) as
      glyceollin elicitors was examined in relation to sulfhydryl oxidation, or
      alteration, and to lipid peroxidation, in 3-d-old soybean hypocotyl/radicle,
      Glycine max. These oxidative events were investigated as possible early steps in
      the transduction mechanisms leading to phytoalexin synthesis. Free protein
      sulfhydryl groups were not modified after any of the eliciting treatments, thus
      indicating that immediate massive protein oxidation or modification cannot be
      considered a signal transduction step. Unlike sulfhydryl reagents, which led to a
      decrease of the free nonprotein sulfhydryl group (free np-SH) pool under all of
      the eliciting conditions, the results obtained with hydroperoxides indicated that
      immediate oxidation of the np-SH is not required for the signal transduction.
      Moreover, elicitation with 10 mM tertbutyl hydroperoxide did not lead to further
      oxidation or to changes in np-SH level during the critical phase of phenylalanine
      ammonialyase activation (the first 20 h), suggesting that np-SH modifications are
      probably not involved in hydroperoxide-induced elicitation. On the other hand,
      all treatments leading to significant glyceollin accumulation were able to
      trigger a rapid (within 2 h) lipid peroxidation process, whereas noneliciting
      treatments did not. In addition, transition metals, such as Fe2+ and Cu+, were
      shown to stimulate both hydrogen peroxide-induced lipid peroxidation and
      glyceollin accumulation, again emphasizing that the two processes are at least
      closely linked in soybean. Among the oxidative processes triggered by activated
      oxygen species, oxidation of sulfhydryl compounds, or lipid peroxidation, our
      results suggest that lipid peroxidation is sufficient to initiate glyceollin
      accumulation in soybean. This further supports the hypothesis that lipid
      peroxidation could be involved as a step in the signal cascade that leads to
      induction of plant defenses.

PMID- 12232140
TI  - Branching Mutant rms-2 in Pisum sativum (Grafting Studies and Endogenous Indole-3
      Acetic Acid Levels).
AB  - Isogenic lines of pea (Pisum sativum L.) were used to determine the physiological
      site of action of the Rms-2 gene, which maintains apical dominance, and its
      effect on endogenous free indole-3-acetic acid (IAA) levels. In mutant rms-2
      scions, which normally produce lateral branches below node 3 and above node 7,
      apical dominance was almost fully restored by grafting to Rms-2 (wild-type)
      stocks. In the reciprocal grafts, rms-2 stocks did not promote branching in wild
      type shoots. Together, these results suggest that the Rms-2 gene inhibits
      branching in the shoot of pea by controlling the synthesis of a translocatable
      (hormone-like) substance that is produced in the roots and/or cotyledons and in
      the shoot. At all stages, including the stage at which aerial lateral buds
      commence outgrowth, the level of IAA in rms-2 shoots was elevated (up to 5-fold)
      in comparison with that in wild-type shoots. The internode length of rms-2 plants
      was 40% less than in wild-type plants, and the mutant plants allocated
      significantly more dry weight to the shoot than to the root in comparison with
      wild-type plants. Grafting to wild-type stocks did not normalize IAA levels or
      internode length in rms-2 scions, even though it inhibited branching, suggesting
      that the involvement of Rms-2 in the control of IAA level and internode length
      may be confined to processes in the shoot.

PMID- 12232141
TI  - Extraction and Isolation of Antifreeze Proteins from Winter Rye (Secale cereale
      L.) Leaves.
AB  - Apoplastic extracts of cold-acclimated winter rye (Secale cereale L. cv
      Musketeer) leaves were previously shown to exhibit antifreeze activity. The
      objectives of the present study were to identify and characterize individual
      antifreeze proteins present in the apoplastic extracts. The highest protein
      concentrations and antifreeze activity were obtained when the leaf apoplast was
      extracted with ascorbic acid and either CaCl2 or MgSO4. Seven major polypeptides
      were purified from these extracts by one-dimensional sodium dodecyl sulfate (SDS)
      polyacrylamide gel electrophoresis under nonreducing conditions. The five larger
      polypeptides, of 19, 26, 32, 34, and 36 kD, exhibited significant levels of
      antifreeze activity, whereas the 11- and 13-kD polypeptides showed only weak
      activity. Five of these polypeptides migrated with higher apparent molecular
      masses on SDS gels after treatment with 0.1 M dithiothreitol, which indicated the
      presence of intramolecular disulfide bonds. The apparent reduction of the
      disulfide bonds did not eliminate antifreeze activity in four of the polypeptides
      that contained intramolecular disulfide bonds and exhibited significant levels of
      antifreeze activity. The amino acid compositions of these polypeptides were
      similar in that they were all relatively enriched in the residues Asp/Asn,
      Glu/Gln, Ser, Thr, Gly, and Ala; they all lacked His, except for the 26-kD
      polypeptide, and they contained up to 5% Cys residues. These polypeptides were
      examined with antisera to other cystine-containing antifreeze proteins from fish
      and insects, and no common epitopes were detected. We conclude that cold
      acclimated winter rye leaves produce multiple polypeptides with antifreeze
      activity that appear to be distinct from antifreezes produced by fish and
      insects.

PMID- 12232142
TI  - Characterization of Sulfate Transport in Chlamydomonas reinhardtii during Sulfur
      Limited and Sulfur-Sufficient Growth.
AB  - We have characterized sulfate transport in the unicellular green alga
      Chlamydomonas reinhardtii during growth under sulfur-sufficient and sulfur
      deficient conditions. Both the Vmax and the substrate concentration at which
      sulfate transport is half of the maximum velocity of the sulfate transport (K1/2)
      for uptake were altered in starved cells: the Vmax increased approximately 10
      fold, and the K1/2 decreased approximately 7-fold. This suggests that sulfur
      deprived C. reinhardtii cells synthesize a new, high-affinity sulfate transport
      system. This system accumulated rapidly; it was detected in cells within 1 h of
      sulfur deprivation and reached a maximum by 6 h. A second response to sulfur
      limited growth, the production of arylsulfatase, was apparent only after 3 h of
      growth in sulfur-free medium. The enhancement of sulfate transport upon sulfur
      starvation was prevented by cycloheximide, but not by chloramphenicol,
      demonstrating that protein synthesis on 80S ribosomes was required for the
      development of the new, high-affinity system. The transport of sulfate into the
      cells occurred in both the light and the dark. Inhibition of ATP formation by the
      antibiotics carbonylcyanide m-chlorophenylhydrazone and gramicidin-S and
      inhibition of either F- or P-type ATPases by N,N-dicyclohexylcarbodiimide and
      vanadate completely abolished sulfate uptake. Furthermore, nigericin, a
      carboxylate ionophore that exchanges H+ for K+, inhibited transport in both the
      light and the dark. Finally, uptake in the dark was strongly inhibited by
      valinomycin. These results suggest that sulfate transport in C. reinhardtii is an
      energy-dependent process and that it may be driven by a proton gradient generated
      by a plasma membrane ATPase.

PMID- 12232143
TI  - Phosphopantethenylated Precursor Acyl Carrier Protein Is Imported into Spinach
      (Spinacia oleracea) Chloroplasts.
AB  - Acyl carrier protein (ACP) is an essential cofactor of fatty acid synthase. In
      plants, ACP is synthesized in the cytosol as a larger precursor protein and then
      is imported into the plastid where it is processed to a smaller mature form. The
      active form of ACP uses a covalently linked 4[prime]-phosphopantetheine
      prosthetic group derived from coenzyme A to covalently bind the acyl
      intermediates during fatty acid synthesis. The prosthetic group is added to ACP
      by holoACP synthase. This enzyme activity is associated with both the plastidial
      subcellular fraction and the soluble, or cytoplasmic, fraction. To gain further
      insight into potential in vivo pathways for the synthesis and maturation of ACP,
      in this study we examined whether precursor holoACP can be imported by isolated
      spinach (Spinacia oleracea) chloroplasts. Precursor holoACP containing a
      [35S]phosphopantetheine prosthetic group was prepared, and the radiolabel was
      used to demonstrate import of the phosphopantethenylated protein into isolated
      chloroplasts. In addition, timed chloroplast import assays indicated that in
      vitro import of the phosphopantethenylated protein is at least as efficient as
      import of the precursor apoprotein. Evidence was also obtained for a low level
      turnover of the prosthetic group among endogenous plastidial ACPs when coenzyme A
      was supplied exogenously.

PMID- 12232144
TI  - Induction of Microsomal Membrane Proteins in Roots of an Aluminum-Resistant
      Cultivar of Triticum aestivum L. under Conditions of Aluminum Stress.
AB  - Three-day-old seedlings of an Al-sensitive (Neepawa) and an Al-resistant (PT741)
      cultivar of Triticum aestivum were subjected to Al concentrations ranging from 0
      to 100 [mu]M for 72 h. At 25 [mu]M Al, growth of roots was inhibited by 57% in
      the Al-sensitive cultivar, whereas root growth in the Al-resistant cultivar was
      unaffected. A concentration of 100 [mu]M Al was required to inhibit root growth
      of the Al-resistant cultivar by 50% and resulted in almost total inhibition of
      root growth in the sensitive cultivar. Cytoplasmic and microsomal membrane
      fractions were isolated from root tips (first 5 mm) and the adjacent 2-cm region
      of roots of both cultivars. When root cytoplasmic proteins were analyzed by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis, no changes in
      polypeptide patterns were observed in response to Al stress. Analysis of
      microsomal membrane proteins revealed a band with an apparent molecular mass of
      51 kD, which showed significant accumulation in the resistant cultivar following
      Al exposure. Two-dimensional gel analysis revealed that this band comprises two
      polypeptides, each of which is induced by exposure to Al. The response of the 51
      kD band to a variety of experimental conditions was characterized to determine
      whether its pattern of accumulation was consistent with a possible role in Al
      resistance. Accumulation was significantly greater in root tips when compared to
      the rest of the root. When seedlings were subjected to Al concentrations ranging
      from 0 to 150 [mu]M, the proteins were evident at 25 [mu]M and were fully
      accumulated at 100 [mu]M. Time-course studies from 0 to 96 h indicated that full
      accumulation of the 51-kD band occurred within 24 h of initiation of Al stress.
      With subsequent removal of stress, the polypeptides gradually disappeared and
      were no longer visible after 72 h. When protein synthesis was inhibited by
      cycloheximide, the 51-kD band disappeared even when seedlings were maintained in
      Al-containing media. Other metals, including Cu, Zn, and Mn, failed to induce
      this band, and Cd and Ni resulted in its partial accumulation. These results
      indicate that synthesis of the 51-kD microsomal membrane proteins is specifically
      induced and maintained during Al stress in the Al-resistant cultivar, PT741.

PMID- 12232145
TI  - Light-Stimulated Cotyledon Expansion in Arabidopsis Seedlings (The Role of
      Phytochrome B).
AB  - Leaf and cotyledon expansion in dicotyledonous plants is a light-dependent
      developmental process. The unique role of phytochrome B has been tested by
      investigating expansion of cotyledons in wild-type and phytochrome-deficient
      mutants of Arabidopsis thaliana (L.) Heynh. A relatively rapid method for
      measuring cotyledon area was developed to quantify growth in large populations
      (average n [greater than or equal to] 100) of wild-type or mutant seedlings under
      different light and chemical treatments. Three-day-old wild-type (La-er)
      Arabidopsis seedlings, grown in saturating, low-fluence red light (2-4 [mu]mol m
      2 s-1), showed a >250% increase in cotyledon area after 48 h of bright-red light
      when compared with the phytochrome mutants hy1, hy2, and hy3. An increase in
      epidermal cell area was observed in wild-type cotyledons but not in hy3,
      indicating that light-stimulated growth is due in part to cell expansion. The
      mutant phenotype was rescued by feeding the chromophore precursor biliverdin to
      the chromophore biosynthesis mutants hy1 and hy6. This treatment did not rescue
      the hy3 mutant. Since the hy3 lesion is specific to phytochrome B, we conclude
      that this pigment is involved in the enhancement of cotyledon cell expansion in
      bright-red light.

PMID- 12232146
TI  - Recovery from Photoinhibition in Peas (Pisum sativum L.) Acclimated to Varying
      Growth Irradiances (Role of D1 Protein Turnover).
AB  - D1 protein turnover and restoration of the photochemical efficiency of
      photosystem II (PSII) after photoinhibition of pea leaves (Pisum sativum L. cv
      Greenfeast) acclimated to different light intensities were investigated. All peas
      acclimated to different light intensities were able to recover from
      photoinhibition, at least partially, at light intensities far above their growth
      light irradiance. However, the capacity of pea leaves to recover from
      photoinhibition under increasing high irradiances was strictly dependent on the
      light acclimation of the leaves; i.e. the higher the irradiance during growth,
      the better the capacity of pea leaves to recover from photoinhibition at moderate
      and high light. In our experimental conditions, mainly D1 protein turnover
      dependent recovery was monitored, since in the presence of an inhibitor of
      chloroplast-encoded protein synthesis, lincomycin, only negligible recovery took
      place. In darkness, neither the restoration of PSII photochemical efficiency nor
      any notable degradation of damaged D1 protein took place. In low light, however,
      good recovery of PSII occurred in all peas acclimated to different light
      intensities and was accompanied by fast degradation of the D1 protein. The rate
      of degradation of the D1 protein was estimated to be 3 to 4 times faster in
      photoinhibited leaves than in nonphotoinhibited leaves under the recovery
      conditions of 50 [mu]mol of photons m-2 s-1. In moderate light of 400 [mu]mol of
      photons m-2 s-1, the photoinhibited low-light peas were not able to increase
      further the rate of D1 protein degradation above that observed in
      nonphotoinhibited leaves, nor was the restoration of PSII function possible. On
      the other hand, photoinhibited high-light leaves were able to increase the rate
      of D1 protein degradation above that of nonphotoinhibited leaves even in moderate
      and high light, ensuring at least partial restoration of PSII function. We
      conclude that the capacity of photoinhibited leaves to restore PSII function at
      different irradiances was directly related to the capacity of the leaves to
      degrade damaged D1 protein under the recovery conditions.

PMID- 12232147
TI  - Effects of Two Strains of Tobacco Mosaic Virus on Photosynthetic Characteristics
      and Nitrogen Partitioning in Leaves of Nicotiana tabacum cv Xanthi during
      Photoacclimation under Two Nitrogen Nutrition Regimes.
AB  - Photoacclimation was studied in tobacco leaves (Nicotiana tabacum cv Xanthi)
      infected with two strains of tobacco mosaic virus (TMV) and grown under different
      light and nitrogen nutrition regimes. Photosynthetic acclimation measured by the
      quantum yield and the maximum rate in saturating light of CO2-saturated
      photosynthesis was impaired to a greater extent in tobacco leaves infected with
      TMV strain PV230 than in those infected with TMV strain PV42. Infection with TMV
      strain PV230 severely impaired photosynthetic acclimation at high light/low
      nitrogen and during transfer from low to high light. Expanding leaves showing
      chlorotic-mosaic symptoms had greatly reduced capacity to acclimate to high light
      compared with controls and with developed leaves without visible symptoms. We
      conclude that the failure of expanding leaves to acclimate was largely due to the
      destruction of chloroplasts in yellow areas of the tissue, accompanied by severe
      reduction in ribulose-1,5-bisphosphate carboxylase/oxygenase levels, and
      corresponding reduction in photosynthesis on a leaf-area basis. When corrected
      for areas of healthy green tissue, photoacclimation of infected leaves was the
      same as that of controls. Visible symptom development was greatest in high
      light/low nitrogen treatments. In developed leaves without visible symptoms,
      virus accumulation, which was as extensive as in expanding leaves, accelerated
      senescence and impaired photoacclimation during transfer from low light to high
      light. Generally, infection with TMV strain PV42 did not impair photosynthetic
      acclimation and even enhanced it in some treatments, even though virus
      accumulated to the same concentration as in PV230-infected leaves. These data
      show that TMV does not simply impair photoacclimation in tobacco by competing
      with chloroplasts for leaf nitrogen reserves. Rather, specific properties of
      severe strains, such as PV230, which lead to visible symptom development and
      patchy loss of photosynthetic activity in expanding leaves as well as general
      acceleration of chloroplast senescence in developed leaves, contribute to
      impaired photoacclimation, which is generally exacerbated by low nitrogen
      nutrition.

PMID- 12232148
TI  - Susceptibility of Tobacco Leaves to Photoinhibition following Infection with Two
      Strains of Tobacco Mosaic Virus under Different Light and Nitrogen Nutrition
      Regimes.
AB  - Sensitivity to photoinhibition under high light stress (2000 [mu]mol photons m-2
      s-1 for 2 h in air) and recovery from this stress were examined in leaves of
      control, uninfected tobacco (Nicotiana tabacum cv Xanthi) leaves and in leaves in
      tobacco plants infected with tobacco mosaic virus (TMV) when grown under low
      light (150-200 [mu]mol photons m-2 s-1) or high light (1200 [mu]mol photons m-2 s
      1) with high (8.0 mM) or low (0.5 mM) nitrate supply. Photoinhibition was
      monitored using the dark-adapted fluorescence parameters variable
      fluorescence/maximum fluorescence, an indicator of photosynthetic efficiency that
      correlated well with the quantum yield of photosynthetic oxygen evolution, and
      initial fluorescence, potentially an indicator of photoinhibitory damage.
      Susceptibility to photoinhibition was greater in low light- and low nitrogen
      grown control plants than in high light- or high nitrogen-treated plants.
      Compared with uninfected controls, infection with the masked strain PV42
      increased susceptibility to photoinhibition only in plants grown under low
      light/low nitrogen conditions. In expanding leaves, infection with severe strain
      TMV PV230 markedly accelerated photoinhibition under these conditions and under
      high light/low nitrogen conditions, even before visible symptoms were evident.
      High nitrogen levels during growth protected against this accelerated
      photoinhibitory response to virus infection during light stress and generally
      promoted recovery, at least prior to symptom development. As symptoms developed,
      the yellow regions provided evidence for chronic photoinhibitory damage, prior to
      and during the stress treatment, irrespective of growth conditions. Green regions
      of leaves showing visible symptoms were generally indistinguishable from control,
      uninfected plants during photoinhibitory stress and recovery. In developed leaves
      that remained free of visible symptoms during the experiments, in spite of the
      accumulation of about the same amounts of virus protein (S. Balachandran, C.B.
      Osmond, A. Makino [1994] Plant Physiol 104: 1043-1050) infection led to an
      acceleration of photoinhibition during stress treatments, especially in low
      light/low nitrogen treatments, in which chronic photoinhibitory damage was
      evident. These studies suggest a role for photoinhibitory damage in the
      acceleration of visible symptom development following TMV PV230 infection of
      expanding leaves, as well as in acceleration of senescence in developed leaves
      without visible symptoms.

PMID- 12232150
TI  - Abscisic Acid and Gibberellin Perception: Inside or Out?

PMID- 12232149
TI  - Diagnosis of the Earliest Strain-Specific Interactions between Tobacco Mosaic
      Virus and Chloroplasts of Tobacco Leaves in Vivo by Means of Chlorophyll
      Fluorescence Imaging.
AB  - Fluorescence imaging was used to diagnose early stages of the strain-specific
      interactions between tobacco mosaic virus (strain PV230) and chloroplasts
      following infection of tobacco leaves (Nicotiana tabacum cv Xanthi). The earliest
      indication of interaction in tissues that ultimately become chlorotic was a
      reduction in chlorophyll fluorescence, and there was little fluorescence
      quenching compared with adjacent healthy tissues. Subsequently, fluorescence
      increased but remained unquenched. In the late stages fluorescence declined again
      in chlorotic regions as the chloroticmosaic symptoms developed. These in vivo
      data showing altered fluorescence yields confirm strain-specific interaction of
      virus coat protein with photosystem II (PSII) components in vitro, leading to
      photoinhibition and photooxidation of chlorophyll in infected cells and the
      development of visible chlorotic-mosaic symptoms. Although mechanisms leading to
      the low, unquenched fluorescence condition are not known, the intermediate high,
      unquenched fluorescence condition is consistent with impaired PSII electron
      transport as measured in vitro. Fluorescence lesions appear more rapidly and
      develop more extensively in high light, consistent with the faster and larger
      extent of symptom formation in high-light-grown leaves than in low-light-grown
      leaves.

PMID- 12232151
TI  - Systemic Acquired Resistance.

PMID- 12232152
TI  - Deconstructing the Cell Wall.

PMID- 12232153
TI  - Low Temperature-Induced Cytoplasmic Acidosis in Cultured Mung Bean (Vigna radiata
      [L.] Wilczek) Cells.
AB  - Cold-induced changes in vivo in the cytoplasmic pH of suspension-cultured cells
      of mung bean (Vigna radiata [L.] Wilczek) were investigated by fluorescence-ratio
      imaging cryomicroscopy with special reference to the variations in the chilling
      sensitivity of cells during the growth cycle. Because of the preferential
      localization of the fluorophore in the cytoplasm under specified conditions and
      the ideal response of fluorescence to pH, fluorescein diacetate allows
      measurements to be made of temporal changes in cytoplasmic pH at low temperature.
      A remarkable difference was demonstrated in the cold-induced changes in
      cytoplasmic pH between cells at the early and late stages of exponential growth.
      The cells at the early stage of exponential growth were most sensitive to
      chilling, and the cytoplasmic pH decreased dramatically within a short period of
      incubation at 0[deg]C, decreasing from 7.4 to 6.8 after 4 h and to 6.3 after 18
      h. The cells at the late stage of exponential growth were chilling tolerant, and
      no significant decrease in the cytoplasmic pH was observed during the incubation
      at 0[deg]C for 24 h or even longer. From the results presented here, it appears
      that cold-induced cytoplasmic acidosis is characteristic of chilling-sensitive
      mung bean suspension-cultured cells.

PMID- 12232155
TI  - Evidence for an Extracellular Reception Site for Abscisic Acid in Commelina Guard
      Cells.
AB  - The phytohormone abscisic acid (ABA) triggers stomatal closing as a physiological
      response to drought stress. Several basic questions limit an understanding of the
      mechanism of ABA reception in guard cells. Whether primary ABA receptors are
      located on the extracellular side of the plasma membrane, within the
      intracellular space of guard cells, or both remains unknown. Furthermore, it is
      not clear whether ABA must be transported into guard cells to exert control over
      stomatal movements. In the present study, a combination of microinjection into
      guard cells and physiological assays of stomatal movements have been performed to
      determine primary sites of ABA reception in guard cells. Microinjection of ABA
      into guard cells of Commelina communis L. resulted in injected cytosolic
      concentrations of 50 to 200 [mu]M ABA and in additional experiments in lower
      concentrations of approximately 1 [mu]M ABA. Stomata with ABA-loaded guard cells
      (n > 180) showed opening similar to stomata with uninjected guard cells. The
      viability of guard cells following ABA injection was demonstrated by neutral red
      staining as well as monitoring of stomatal opening. Extracellular application of
      10 [mu]M ABA inhibited stomatal opening by 98% at pH 6.15 and by 57% at pH 8.0.
      The pH dependence of extracellular ABA action may suggest a contribution of an
      intracellular ABA receptor to stomatal regulation. The findings presented here
      show that intracellular ABA alone does not suffice to inhibit stomatal opening
      under the imposed conditions. Furthermore, these data provide evidence that a
      reception site for ABA-mediated inhibition of stomatal opening is on the
      extracellular side of the plasma membrane of guard cells.

PMID- 12232154
TI  - Phytochrome A and Phytochrome B Have Overlapping but Distinct Functions in
      Arabidopsis Development.
AB  - Plant responses to red and far-red light are mediated by a family of
      photoreceptors called phytochromes. In Arabidopsis thaliana, there are genes
      encoding at least five phytochromes, and it is of interest to learn if the
      different phytochromes have overlapping or distinct functions. To address this
      question for two of the phytochromes in Arabidopsis, we have compared light
      responses of the wild type with those of a phyA null mutant, a phyB null mutant,
      and a phyA phyB double mutant. We have found that both phyA and phyB mutants have
      a deficiency in germination, the phyA mutant in far-red light and the phyB mutant
      in the dark. Furthermore, the germination defect caused by the phyA mutation in
      far- red light could be suppressed by a phyB mutation, suggesting that
      phytochrome B (PHYB) can have an inhibitory as well as a stimulatory effect on
      germination. In red light, the phyA phyB double mutant, but neither single
      mutant, had poorly developed cotyledons, as well as reduced red-light induction
      of CAB gene expression and potentiation of chlorophyll induction. The phyA mutant
      was deficient in sensing a flowering response inductive photoperiod, suggesting
      that PHYA participates in sensing daylength. In contrast, the phyB mutant
      flowered earlier than the wild type (and the phyA mutant) under all photoperiods
      tested, but responded to an inductive photoperiod. Thus, PHYA and PHYB appear to
      have complementary functions in controlling germination, seedling development,
      and flowering. We discuss the implications of these results for possible
      mechanisms of PHYA and PHYB signal transduction.

PMID- 12232156
TI  - Perception of Gibberellin and Abscisic Acid at the External Face of the Plasma
      Membrane of Barley (Hordeum vulgare L.) Aleurone Protoplasts.
AB  - The response of protoplasts isolated from aleurone layers of barley (Hordeum
      vulgare L. cv Himalaya) to internally and externally applied hormone was analyzed
      to localize the site of perception of the hormonal signal. Protoplasts responded
      to externally applied gibberellic acid (GA3) with increased synthesis and
      secretion of [alpha]-amylase, transient expression of the glucuronidase reporter
      gene fused to the hormone-responsive elements of the [alpha]-amylase promoter,
      and the vacuolation typical of GA3-treated aleurone cells. When up to 250 [mu]M
      GA3 was microinjected into the protoplast cytoplasm, none of these responses were
      observed. This did not reflect damage to the protoplasts during the
      microinjection procedure, since microinjected protoplasts remained responsive to
      externally applied hormone. Nor did it reflect loss of microinjected GA3 from the
      protoplast, since 50% of microinjected [3H]GA20 was retained by protoplasts for
      at least 24 h. Externally applied abscisic acid (ABA) could reverse the
      stimulation of [alpha]-amylase synthesis and secretion, whereas microinjecting up
      to 250 [mu]M ABA was ineffective at antagonizing the stimulatory effect of GA3.
      These results suggest that the site of perception of GA3 and ABA in the barley
      aleurone protoplast is on the external face of the plasma membrane.

PMID- 12232157
TI  - Altered Phase Behavior in Membranes of Aging Dry Pollen May Cause Imbibitional
      Leakage.
AB  - Aging of dry pollen has been shown to coincide with increases of free fatty acids
      and lysophospholipids. These compounds reduce the integrity of hydrated liposomes
      made from isolated pollen phospholipids but do not lead to their total
      destruction. However, a massive, instantaneous leakage occurs upon imbibition of
      dry cattail pollen (Typha latifolia) that has aged to the point of complete loss
      of viability. To resolve the apparent discrepancy in stability between hydrated
      and dry membranes, the lyotropic phase behavior of two liposome systems
      containing lysophospholipid (12 mol%) was studied with differential scanning
      calorimetry and Fourier transform infrared spectroscopy. In both systems
      dehydration caused phase separation of the lipids. Fourier transform infrared
      data concerning phase behavior of isolated membranes from aging pollen and of
      membranes in situ did not show phase separations, probably because the assay
      technique was not sufficiently sensitive to detect them. However, aging of the
      pollen resulted in a permanent increase in the gel-to-liquid crystalline phase
      transition temperature (Tm) of isolated membranes and in a broadening of the
      transition in situ. We conclude that the increase in Tm of hydrated membranes may
      be more closely related to the leakage.

PMID- 12232158
TI  - Cells of the Upper and Lower Epidermis of Barley (Hordeum vulgare L.) Leaves
      Exhibit Distinct Patterns of Vacuolar Solutes.
AB  - Vacuolar saps were extracted from individual, anatomically uniform cells of the
      upper (adaxial) and lower (abaxial) epidermis of the third leaf of barley
      (Hordeum vulgare L.) using a modified pressure probe. Saps (volume 80-200 pL)
      were sampled at various times between 3 d before and 7 d after full-leaf
      expansion and were analyzed for their osmolality and their concentrations of NO3
      , malate, CI-, K+, and Ca2+. The osmolalities of upper and lower epidermis both
      increased with time but were similar to each other. In young leaves, K+ and Ca2+
      were evenly distributed between the two epidermal layers, but as the leaf aged,
      the upper epidermis accumulated high (40-100 mM) Ca2+, whereas cells of the lower
      epidermis accumulated K+ instead. Nitrate concentration was 100 to 150 mM higher
      in the upper than in the lower epidermis, whereas CI- was 50 to 120 mM higher in
      the lower epidermis. These differences did not depend on the leaf developmental
      stage. The uneven distribution of epidermal NO3- and CI- was maintainedover a
      wide range of epidermal sap concentrations of these ions and was not affected by
      NO3- or CI- starvation or by an increase in the light intensity from 120 to 400
      [mu]mol m-2 s-1. However, the latter did cause a decrease in epidermal NO3- and
      the appearance and accumulation of epidermal malate, particularly in the upper
      epidermis. The physiological implications of the results for solute storage in
      leaves and for the pathways of ion distribution to the epidermis are discussed.

PMID- 12232159
TI  - Action Spectra of Photosystems I and II in State 1 and State 2 in Intact Sugar
      Maple Leaves.
AB  - Photochemical activity, measured as energy storage of photosystems I (PSI) and II
      (PSII) together and individually, is studied in sugar maple (Acer saccharum
      Marsh.) leaves in the spectral range between 400 and 700 nm in state 1 and state
      2. Total photochemical activity remains the same in both state 1 and state 2
      between 580 and 700 nm, but it is lower in state 2 between 400 and 580 nm. Both
      PSI and PSII activities change significantly during the state transition due to
      the migration of light-harvesting chlorophyll a/b protein complex of PSII
      (LHCII). In the action spectra of PSI and PSII, peak positions vary depending on
      the association or dissociation of LHCII, except for the peak at 470 nm in the
      PSII spectrum. PSII activity is about 3 times higher than or equal to PSI in
      state 1 or state 2, respectively, over most of the spectrum except in the blue
      and far-red regions. At 470 nm, PSII activity is 8 or 1.6 times higher than PSI
      in state 1 or state 2, respectively. The amplitude of LHCII coupling-induced
      change is the same in both PSI and PSII between 580 and 700 nm, but it is less in
      PSI than in PSII between 400 and 580 nm, which explains the lower photochemical
      activity of the leaf in state 2 than in state 1. This may be due to a decrease in
      energy transfer efficiency of carotenoids to chlorophylls in LHCII when it is
      associated with PSI.

PMID- 12232160
TI  - Purification and Properties of Cystathionine [gamma]-Synthase from Wheat
      (Triticum aestivum L.).
AB  - Cysthathionine [gamma]-synthase (CS), an enzyme involved in methionine
      biosynthesis, was purified from an acetone powder prepared from wheat (Triticum
      aestivum L.). After several chromatographic steps and radiolabeling of the
      partially purified enzyme with sodium cyanoboro[3H]hydride, a single polypeptide
      with a molecular weight of 34,500 was isolated by sodium dodecyl sulfate-high
      performance electrophoresis chromatography. Since the molecular weight of the
      native enzyme was 155,000, CS apparently consists of four identical subunits. The
      pyridoxal 5[prime]-phosphate-dependent forward reaction has a pH optimum of 7.5
      and follows a hybrid ping-pong mechanism with Km values of 3.6 mM and 0.5 mM for
      L-homoserine phosphate and L-cysteine, respectively. L-Cysteine methyl ester,
      thioglycolate methyl ester, and sodium sulfide were also utilized as thiol
      substrates. The latter observation suggests that CS and phosphohomoserine
      sulfhydrase might be a single enzyme. CS does not seem to be a regulatory enzyme
      but was irreversibly inhibited by DL-propargylglycine (Ki = 45 [mu]M, Kinact =
      0.16 min-1). Furthermore, the homoserine phosphate analogs 4-(phosphonomethyl)
      pyridine-2-carboxylic acid, Z-3-(2-phosphonoethen-1-yl)pyridine-2-carboxylic
      acid, and DL-E-2-amino-5-phosphono-3-pentenoic acid acted as reversible
      competitive inhibitors with Ki values of 45, 40, and 1.1 [mu]M, respectively.

PMID- 12232161
TI  - Characteristics of Modified Leghemoglobins Isolated from Soybean (Glycine max
      Merr.) Root Nodules.
AB  - Hemoprotein derivatives of an abundant soybean (Glycine max Merr.) root nodule
      leghemoglobin, Lba, were studied for their modified spectral characteristics and
      physical properties. Three modified hemoprotein derivatives of Lba (Lbam1, Lbam2,
      and Lbam3) were purified by preparative isoelectric focusing. The ferric forms of
      these pigments were green and exhibited anomalous spectra in the visible region
      as compared to the Lba3+ forms. These modified pigments showed a hypochromic
      shift of 10 nm for the charge transfer absorption maximum; however, differences
      were not apparent in the Soret region. Upon binding with nicotinate, the [alpha]
      and [beta] bands were shifted significantly into the red region as compared to
      the Lba3+ nicotinate complex. The three Lbam fractions were reduced by dithionite
      or by NADH in the presence of riboflavin. Lbam2+ also bound nicotinate and
      displayed absorption spectra indistinguishable from those of Lba2+ nicotinate. In
      contrast to Lba2+, Lbam2+ displayed aberrant spectra when bound with either O2 or
      CO. These complexes exhibited a prominent charge transfer band at approximately
      620 nm and failed to exhibit spectra characteristic of Lba2+O2 and Lba2+CO. The
      protein moiety of these modified pigments was intact because their
      tyrosine/tryptophan ratios and their amino acid compositions were identical with
      those of Lba, nor were differences observed in the peptide profiles resulting
      from trypsin digests of purified Lba and Lbams. Automated Edman degradation of
      selected peaks further confirmed the intactness of the protein backbone including
      the absence of deamination. Pyridine hemochromogen for heme from Lbams could be
      formed, and the spectra displayed distinct differences compared to those of Lba.
      A new peak at 580 nm and a loss of a peak at 480 nm were observed for all three
      Lbams.

PMID- 12232162
TI  - Involvement of de Novo Protein Synthesis, Protein Kinase, Extracellular Ca2+, and
      Lipoxygenase in Arachidonic Acid Induction of 3-Hydroxy-3-Methylglutaryl Coenzyme
      A Reductase Genes and Isoprenoid Accumulation in Potato (Solanum tuberosum L.).
AB  - A series of inhibitors were tested to determine the participation of de novo
      protein synthesis, protein kinase activity, extracellular Ca2+, and lipoxygenase
      activity in arachidonic acid elicitation of 3-hydroxy-3-methylglutaryl coenzyme A
      reductase (HMGR) gene expression and sesquiterpene phytoalexin biosynthesis in
      potato (Solanum tuberosum L. cv Kennebec). Gene-specific probes were used to
      discriminate effects on the expression of two HMGR genes (hmg1 and hmg2) that
      respond differentially in tuber tissue following wounding or elicitor treatment.
      Inhibition of protein synthesis with cycloheximide completely blocked
      arachidonate-induced hypersensitive necrosis and browning, including HMGR gene
      induction and phytoalexin accumulation. This suggests that proteins necessary for
      coupling arachidonic acid reception to HMGR mRNA accumulation are either rapidly
      turned over or not present constitutively and are induced following elicitor
      treatment. Staurosporin, a potent inhibitor of protein kinases, and
      ethyleneglycol-bis([beta]-aminoethyl ether)-N,N[prime]-tetraacetic acid, a Ca2+
      chelator, inhibited arachidonate-induction of hmg2 gene expression and
      phytoalexin accumulation but did not inhibit the wound-induced expression of
      hmg1. However, staurosporin inhibited arachidonate's suppression of hmg1 gene
      expression. Eicosatetraynoic acid, a lipoxygenase inhibitor that suppresses
      elicitor-induced phytoalexin accumulation, also inhibited arachidonate's
      suppression of hmg1 and induction of hmg2. The results indicate that
      arachidonate's suppression of hmg1 and activation of hmg2 depend on a common
      intermediate or set of intermediates whose generation is sensitive to the
      inhibitors tested.

PMID- 12232163
TI  - Protein Phosphorylation Is Induced in Tobacco Cells by the Elicitor Cryptogein.
AB  - Changes in plasmalemma ion fluxes were observed when tobacco (Nicotiana tabacum)
      cells were treated with cryptogein, a proteinaceous elicitor from Phytophthora
      cryptogea. A strong alkalization of the culture medium, accompanied by a leakage
      of potassium, was induced within a few minutes of treatment. These effects
      reached a maximum after 30 to 40 min and lasted for several hours. This treatment
      also resulted in a rapid, but transient, production of activated oxygen species.
      All these physiological responses were fully sensitive to staurosporine, a known
      protein kinase inhibitor. Furthermore, a study of protein phosphorylation showed
      that cryptogein induced a staurosporine-sensitive phosphorylation of several
      polypeptides. These data suggest that phosphorylated proteins may be essential
      for the transduction of elicitor signals.

PMID- 12232164
TI  - Blue-Light Regulation of the Arabidopsis thaliana Cab1 Gene.
AB  - The steady-state level of Cab RNA in etiolated Arabidopsis thaliana increases as
      a result of a single pulse of blue light. The threshold for the response is at or
      below 10[deg] [mu]mol m-2 and begins within 1 h of irradiation. The response is
      not prevented by far-red treatment, and the blue-light source used does not
      elicit and observable very low fluence phytochrome response for RbcS RNA. The
      time course for blue-light-induced transcript accumulation differs from that of
      red, the blue beginning more quickly. Transcripts derived from the Cab1 (AB140;
      Lhcb1*3) member of the gene family are responsible in part for the blue-light
      induced accumulation. This is the same member of the gene family that is
      responsible for phytochrome-induced Cab gene expression (G.A. Karlin-Neumann, L.
      Sun, E.M. Tobin [1988] Plant Physiol 88: 1323-1331). The mutant hy4, which lacks
      blue-light-induced suppression of hypocotyl elongation, retains the ability of
      Cab RNA to respond to blue light.

PMID- 12232165
TI  - In Vitro Analysis of Light-Induced Transcription in the Wheat psbD/C Gene Cluster
      Using Plastid Extracts from Dark-Grown and Short-Term-Illuminated Seedlings.
AB  - We describe a plastid in vitro transcription system that reflects characteristic
      features of the light-regulated transcription observed in vivo. Multiple
      transcripts of the wheat (Triticum aestivum) psbD/C gene cluster comprise six
      distinct 5[prime] ends including four transcription initiation sites designated
      as D/C-1 through D/C-4. Transcripts from one particular site, D/C-3, were found
      to be conspicuously enhanced in abundance after 4 h of illumination in vivo. The
      plastid extract prepared from 5-d-old dark-grown wheat seedlings was capable of
      transcribing from the D/C-2 and D/C-4 sites in vitro but had almost no
      transcription activity from the light-responsive D/C-3 site (the D/C-1 site was
      not examined). The plastid extract from 4-h-illuminated seedlings initiated
      transcription from the light-responsive site (D/C-3). Transcription from the D/C
      2 and D/C-4 sites was not enhanced by using the extract from 4-h-illuminated
      seedlings, indicative of specific activation of the light-responsive promoter on
      the D/C-3 site by the extract from 4-h-illuminated seedlings. The plastid extract
      from 4-h-illuminated seedlings was divided into two fractions on a heparin
      Sepharose column, into which the light-induced component(s) responsible for
      activation of the D/C-3 promoter and RNA polymerase were separated. The fraction
      containing the component(s) activating the D/C-3 promoter induced the
      transcription activity from the D/C-3 site in the plastid extract from dark-grown
      seedlings. It is concluded that the plastid extract from 4-h-illuminated
      seedlings contains some light-regulatory component(s) that activate specifically
      the light-responsive promoter.

PMID- 12232166
TI  - Histochemical Demonstration and Localization of H2O2 in Organs of Higher Plants
      by Tissue Printing on Nitrocellulose Paper.
AB  - A sensitive tissue-print assay for the detection and histological localization of
      H2O2 in freshly cut organ sections was developed by impregnating nitrocellulose
      paper with a mixture of Kl and soluble starch. H2O2 transferred from the cut
      surface of the section to the dried paper forms I2, which can be visualized by
      the intensely colored I2-starch complex. The detection limit of the assay is in
      the range of 0.1 to 0.2 mmol L-1 H2O2. Due to the rapid immobilization of H2O2 in
      the paper, very clear prints of the tissue distribution of H2O2 can be obtained
      with a spatial resolution on the level of single cells. The application of this
      rapid and simple assay is explored in five experimental examples demonstrating
      that the in vivo level of H2O2 varies strikingly in different tissues and can be
      regulated by developmental factors such as hormones, light, and wounding. The
      results show that: (a) In the hypocotyl of soybean (Glycine max L.) seedlings the
      apoplastic H2O2 level increases strongly from top to base, accompanied by
      characteristic changes in its histological distribution. (b) In the epicotyl of
      pea (Pisum sativum L.) seedlings the induction of lateral expansion by ethylene
      is correlated with a depletion of H2O2 in the cell walls of the expanding
      tissues. (c) In the hypocotyl of bean (Phaseolus vulgaris L.) seedlings H2O2 is
      primarily localized in a ring of parenchymatic tissue between xylem and cortex
      next to lignifying cells but not in the lignifying cells themselves. (d) In the
      hypocotyl of sunflower (Helianthus annuus L.) and cucumber (Cucumis sativus L.)
      seedlings the light-mediated inhibition of elongation growth is correlated with a
      strong increase in H2O2 in the epidermis and in the vascular bundles. (e) Potato
      (Solanum tuberosum L.) tubers show high levels of H2O2 only in the outer cell
      layers but are able to accumulate H2O2 in the inner tissue upon wounding.

PMID- 12232167
TI  - Modulation of H+-ATPase Activity by Fusicoccin in Plasma Membrane Vesicles from
      Oat (Avena sativa L.) Roots (A Comparison of Modulation by Fusicoccin, Trypsin,
      and Lysophosphatidylcholine).
AB  - The fungal phytotoxin fusicoccin affects various transport processes in the
      plasma membrane of plant cells. The plasma membrane (PM) H+-ATPase (EC 3.6.1.35)
      seems to be the primary target of fusicoccin action. The kinetics of the
      stimulation of the PM H+-ATPase by fusicoccin was studied in PM vesicles isolated
      from oat (Avena sativa cv Adamo) roots by aqueous two-phase partitioning.
      Considerable stimulation of activity was observed only when roots were treated
      with fusicoccin prior to the PM isolation. Fusicoccin treatment shifted the pH
      optimum of the ATPase toward more alkaline values and increased Vmax. No effects
      on Km were observed. Treatment with trypsin resulted in stimulation of ATPase
      activity in control vesicles but not in the fusicoccin-treated vesicles. The
      characteristics of stimulation by trypsin in control vesicles were comparable
      with those of stimulation by fusicoccin. This result and the change of the
      polypeptide pattern on western blots suggest the involvement of the C-terminal
      inhibitory domain in the fusicoccin signal transduction chain. On the other hand,
      stimulation by lyso-PC demonstrated other characteristics than stimulation by
      fusicoccin. Lyso-PC was able to stimulate ATPase activity at both acidic and
      alkaline pH values. Kinetic analysis of the pH dependency curves revealed
      different mechanisms for activation by fusicoccin and by lyso-PC. Whereas
      fusicoccin shifted the pH dependency of formation of phosphorylated intermediate
      to more alkaline values, lyso-PC seemed to increase dephosphorylation
      independently of pH.

PMID- 12232168
TI  - A Study of the Effect of Inhibitors of the Animal Sarcoplasmic/Endoplasmic
      Reticulum-Type Calcium Pumps on the Primary Ca2+-ATPases of Red Beet.
AB  - The inhibitor sensitivity of the endoplasmic reticulum (ER) and plasma membrane
      (PM) calcium pumps of red beet (Beta vulgaris L.) were studied by measuring the
      ATP-driven accumulation of 45Ca2+ into isolated membrane vesicles. Both
      transporters were strongly inhibited by 50 [mu]mol m-3 erythrosin B, but only by
      50% in the presence of 100 mmol m-3 vanadate. A number of inhibitors considered
      to be specific for the sarcoplasmic reticulum (SR)/ER-type calcium pump in animal
      cells were used to further characterize the PM and ER Ca2+-ATPases in red beet
      and were compared with their effect on the transport and hydrolytic activities of
      the PM and tonoplast H+-ATPases. The hydroquinones 2,5-di(tert-butyl)-1,4
      benzohydroquinone and 2,5-di(tert-amyl)-1,4-benzohydroquinone produced around 20
      and 40% inhibition of activity, respectively, of the PM and ER calcium pumps and
      the PM H+-ATPase when present at concentrations of 30 mmol m-3. In contrast, the
      vacuolar proton pump displayed a much higher sensitivity to these two compounds.
      Nonylphenol appeared to have a general inhibitory effect on all four membrane
      transport proteins and gave almost complete inhibition when present at a
      concentration of 100 mmol m-3. Thapsigargin and the structurally related compound
      trilobolide produced 50% inhibition of both the ER and PM calcium pumps at
      concentrations of 12.5 and 24 mmol m-3, respectively. The PM and tonoplast proton
      pumps were also sensitive to these compounds. The ER and PM calcium pumps were
      almost completely insensitive to cyclopiazonic acid (CPA) up to a concentration
      of 20 mmol m-3. When present at 100 mmol m-3 CPA caused 30% inhibition of the
      transport properties of all four ATPases. The high concentrations of all of the
      inhibitors of the SR/ER Ca-ATPase required to inhibit the red beet ER calcium
      pump, together with the similar effects on the PM calcium pump and the PM and
      tonoplast proton pumps, suggests that these hydrophobic compounds have a general
      nonselective action in red beet, possibly through disruption of membrane lipid
      protein interactions.

PMID- 12232169
TI  - Detoxification of Formaldehyde by the Spider Plant (Chlorophytum comosum L.) and
      by Soybean (Glycine max L.) Cell-Suspension Cultures.
AB  - The phytotoxicity of formaldehyde for spider plants (Chlorophytum comosum L.),
      tobacco plants (Nicotiana tabacum L. cv Bel B and Bel W3), and soybean (Glycine
      max L.) cell-suspension cultures was found to be low enough to allow metabolic
      studies. Spider plant shoots were exposed to 7.1 [mu]L L-1 (8.5 mg m-3) gaseous
      [14C]-formaldehyde over 24 h. Approximately 88% of the recovered radioactivity
      was plant associated and was found to be incorporated into organic acids, amino
      acids, free sugars, and lipids as well as cell-wall components. Similar results
      were obtained upon feeding [14C]formaldehyde from aqueous solution to aseptic
      soybean cell-suspension cultures. Serine and phosphatidylcholine were identified
      as major metabolic products. Spider plant enzyme extracts contained two NAS+
      dependent formaldehyde dehydrogenase activities with molecular mass values of
      about 129 and 79 kD. Only the latter enzyme activity required glutathione as an
      obligatory second cofactor. It had an apparent Km value of 30 [mu]M for
      formaldehyde and an isoelectric point at pH 5.4. Total cell-free dehydrogenase
      activity corresponded to 13 [mu]g formaldehyde oxidized h-1 g-1 leaf fresh
      weight. Glutathione-dependent formaldehyde dehydrogenases were also isolated from
      shoots and leaves of Equisetum telmateia and from cell-suspension cultures of
      wheat (Triticum aestivum L.) and maize (Zea mays L.). The results obtained are
      consistent with the concept of indoor air decontamination with common room plants
      such as the spider plant. Formaldehyde appears to be efficiently detoxified by
      oxidation and subsequent C1 metabolism.

PMID- 12232170
TI  - Phytochrome B and at Least One Other Phytochrome Mediate the Accelerated
      Flowering Response of Arabidopsis thaliana L. to Low Red/Far-Red Ratio.
AB  - We have investigated the involvement of phytochrome B in the early-flowering
      response of Arabidopsis thaliana L. seedlings to low red:far-red (R/FR) ratio
      light conditions. The phytochrome B-deficient hy3 (phyB) mutant is early
      flowering, and in this regard it resembles the shade-avoidance phenotype of its
      isogenic wild type. Seedlings carrying the hy2 mutation, resulting in a
      deficiency of phytochrome chromophore and hence of active phytochromes, also
      flower earlier than wild-type plants. Whereas hy3 or hy2 seedlings show only a
      slight acceleration of flowering in response to low R/FR ratio, seedlings that
      are doubly homozygous for both mutations flower earlier than seedlings carrying
      either phytochrome-related mutation alone. This additive effect clearly indicates
      the involvement of one or more phytochrome species in addition to phytochrome B
      in the flowering response as well as indicating the presence of some functional
      phytochrome B in hy2 seedlings. Seedlings that are homozygous for the hy3
      mutation and one of the fca, fwa, or co late-flowering mutations display a
      pronounced early-flowering response to low R/FR ratio. A similar response to low
      R/FR ratio is displayed by seedlings doubly homozygous for the hy2 mutation and
      any one of the late-flowering mutations. Thus, placing the hy3 or hy2 mutations
      into a late-flowering background has the effect of uncovering a flowering
      response to low R/FR ratio. Seedlings that are triply homozygous for the hy3, hy2
      mutations and a late-flowering mutation flower earlier than the double mutants
      and do not respond to low R/FR ratio. Thus, the observed flowering responses to
      low R/FR ratio in phytochrome B-deficient mutants can be attributed to the action
      of at least one other phytochrome species.

PMID- 12232171
TI  - Blue Light Induces Phosphorylation at Seryl Residues on a Pea (Pisum sativum L.)
      Plasma Membrane Protein.
AB  - We have partially characterized the blue-light-stimulated in vitro
      phosphorylation of a membrane protein from etiolated Pisum sativum L. stems.
      Properties of the response have implicated its involvement in signal transduction
      of phototropic stimuli (T.W. Short, W.R. Briggs [1990] Plant Physiol 92: 179-185;
      P. Reymond, T.W. Short, W.R. Briggs [1992] Proc Natl Acad Sci USA 89: 4718-
      4721). Analysis of proteolysis products and phosphoamino acidanalysis indicate
      that the substrate protein is phosphorylated on multiple seryl residues. Kinetics
      of the in vitro reaction show phosphorylation to be complete within 2 to 5 min at
      30[deg]C in either light-exposed or dark-control plasma membrane preparations,
      regardless of whether the membranes were first solubilized in Triton X-100.
      Nucleotide competition assays show the kinase to be ATP specific. The pH optimum
      covers a broad range with a maximum near 7.5. A wide array of salts inhibits the
      phosphorylation at high concentrations, but millimolar concentrations of Mg2+ are
      required to form Mg.ATP complexes for maximal activity, whereas excess free Mg2+
      or Ca2+ are not required for the reaction.

PMID- 12232172
TI  - The Involvement of Respiration in Free Radical Processes during Loss of
      Desiccation Tolerance in Germinating Zea mays L. (An Electron Paramagnetic
      Resonance Study).
AB  - When germinating Zea mays L. seeds are rapidly desiccated, free radical-mediated
      lipid peroxidation and phospholipid de-esterification is accompanied by a
      desiccation-induced buildup of a stable free radical associated with rapid loss
      of desiccation tolerance. Comparison of the electron paramagnetic resonance and
      electron nuclear double resonance properties of this radical with those of the
      radical in dried, desiccation-intolerant moss showed that the two were identical.
      At the subcellular level, the radical was associated with the hydrophilic
      fraction resulting from lipid extraction. Isolated mitochondria subjected to
      drying were also found to accumulate an identical radical in vitro. When
      increasing concentrations of cyanide were used, a significant positive
      correlation was shown between rates of respiration and the accumulation of the
      radical in desiccation-intolerant tissues. Another positive correlation was found
      when rates of O2 uptake by radicles at different stages of germination were
      plotted against free radical content following desiccation. This indicates that
      free radical production is closely linked to respiration in a process likely to
      involve the desiccation-induced impairment of the mitochondrial electron
      transport chain to form thermodynamically favorable conditions to induce
      accumulation of a stable free radical and peroxidized lipids. Modulation of
      respiration using a range of inhibitors resulted in broadly similar modulation of
      the buildup of the stable free radical. One site of radical generation was likely
      to be the NADH dehydrogenase of complex I and probably as a direct consequence of
      desiccation-impaired electron flow at or close to the ubiquinone pool.

PMID- 12232173
TI  - Alterations in Water Status, Endogenous Abscisic Acid Content, and Expression of
      rab18 Gene during the Development of Freezing Tolerance in Arabidopsis thaliana.
AB  - Treatments as diverse as exposure to low temperature (LT), exogenous abscisic
      acid (ABA), or drought resulted in a 4 to 5[deg]C increase in freezing tolerance
      of the annual herbaceous plant Arabidopsis thaliana. To correlate the increase in
      freezing tolerance with the physiological changes that occur in response to these
      treatments, we studied the alterations in water status, endogenous ABA levels,
      and accumulation of rab18 (V. Lang and E.T. Palva [1992] Plant Mol Biol 20: 951
      962) mRNA. Exposure to LT and exogenous ABA caused only a minor decline in total
      water potential ([psi]w), in contrast to a dramatic decrease in [psi]w during
      drought stress. Similarly, the endogenous ABA levels were only slightly and
      transiently increased in LT-treated plants in contrast to a massive increase in
      ABA levels in drought-stressed plants. The expression of the ABA-responsive rab18
      gene was low during the LT treatment but could be induced to high levels by
      exogenous ABA and drought stress. Taken together, these results suggest that the
      moderate increases in freezing tolerance of A. thaliana might be achieved by
      different mechanisms. However, ABA-deficient and ABA-insensitive mutants of A.
      thaliana have impaired freezing tolerance, suggesting that ABA is, at least
      indirectly, required for the development of full freezing tolerance.

PMID- 12232174
TI  - Phosphoinositides in Barley (Hordeum vulgare L.) Aleurone Tissue.
AB  - [3H]Inositol labeling of barley (Hordeum vulgare L. cv Himalaya) aleurone layers
      and analysis of phospholipids by deacylation revealed the presence of
      phosphatidylinositol (PtdIns), PtdIns3P, and PtdIns4P but not PtdInsP2 species.
      In contrast to an earlier report (P.P.N. Murthy, G. Pliska-Matyshak, L.M.
      Keranen, P. Lam, H.H. Mueller, N. Bhuvarahamurthy [1992] Plant Physiol 98: 1498
      1501) systematic chemical degradation of PtdIns revealed no evidence of a second
      isomer of PtdIns. Evidence of the widespread occurrence of 3-phosphorylated
      PtdIns within the plant kingdom is presented.

PMID- 12232175
TI  - Hydraulic Signals from the Roots and Rapid Cell-Wall Hardening in Growing Maize
      (Zea mays L.) Leaves Are Primary Responses to Polyethylene Glycol-Induced Water
      Deficits.
AB  - We investigated mechanisms involved in inhibition of maize (Zea mays L.) leaf
      elongation growth following addition of non-penetrating osmolyte to the root
      medium. The elongation rate of the first true leaf remained inhibited for 4 h
      after addition of polyethylene glycol 6000 (PEG; -0.5 MPa water potential),
      despite progressive osmotic adjustment in the growing leaf tissues. Thus,
      inhibition of leaf growth did not appear to be directly related to loss of leaf
      capacity to maintain osmotic potential gradients. Comparative cell-wall-extension
      capacities of immature (still expanding) leaf tissues were measured by creep
      extensiometry using whole plants. Reductions in irreversible (plastic) extension
      capacity (i.e. wall hardening) were detected minutes and hours after addition of
      PEG to the roots, by both in vivo and in vitro assay. The onset of the wall
      hardening response could be detected by in vitro assay only 2 min after addition
      of PEG. Thus, initiation of wall hardening appeared to precede transcription
      regulated responses. The inhibition of both leaf growth and wall-extension
      capacity was reversed by removal of PEG after 4 h. Moreover, wall hardening could
      be induced by other osmolytes (mannitol, NaCl). Thus, the leaf responses did not
      appear to be related to any specific (toxic) effect of PEG. We conclude that
      hardening of leaf cell walls is a primary event in the chain of growth regulatory
      responses to PEG-induced water deficits in maize. The signaling processes by
      which PEG, which is not expected to penetrate root cell walls or membranes, might
      cause cell-wall hardening in relatively distant leaves was also investigated.
      Plants with live or killed roots were exposed to PEG. The killed roots were
      presumed to be unable to produce hormonal or electrical signals in response to
      addition of PEG; however, inhibition of leaf elongation and hardening of leaf
      cell walls were detected with both live and killed roots. Thus, neither hormonal
      signaling nor signaling via induced changes in surface electrical potential were
      necessary, and hydraulic signals appeared to generate the leaf responses.

PMID- 12232176
TI  - Correlation of Carbonic Anhydrase and Ribulose-1,5-Bisphosphate
      Carboxylase/Oxygenase Expression in Pea.
AB  - The enzyme carbonic anhydrase (carbonate dehydratase, EC 4.2.1.1) is an abundant
      soluble protein in the C3 plant chloroplast; however, its function in
      photosynthetic carbon assimilation is not well defined. In this study we have
      examined the relationship between carbonic anhydrase (CA) and ribulose-1,5
      bisphosphate carboxylase/oxygenase (Rubisco) expression during pea (Pisum
      sativum) development as well as in various tissues and cultivars. Although
      absolute levels of activity and transcript abundance for the two proteins can
      vary considerably during development, a relatively constant ratio of CA to
      Rubisco transcript abundance and enzyme activity appears to be initiated during
      greening and maintained in mature and senescing photosynthetic tissue. Various
      pea cultivars, although exhibiting differing amounts of Rubisco and CA, also
      appear to maintain an invariant CA:Rubisco ratio. These data are discussed with
      respect to gene copy number, regulation of expression, and the proposed role of
      CA in photosynthetic carbon fixation.

PMID- 12232177
TI  - Monensin Inhibition of Na+-Dependent HCO3- Transport Distinguishes It from Na+
      Independent HCO3- Transport and Provides Evidence for Na+/HCO3- Symport in the
      Cyanobacterium Synechococcus UTEX 625.
AB  - The effect of monensin, an ionophore that mediates Na+/H+ exchange, on the
      activity of the inorganic carbon transport systems of the cyanobacterium
      Synechococcus UTEX 625 was investigated using transport assays based on the
      measurement of chlorophyll a fluorescence emission or 14C uptake. In
      Synechococcus cells grown in standing culture at about 20 [mu]M CO2 + HCO3-, 50
      [mu]M monensin transiently inhibited active CO2 and Na+-independent HCO3-
      transport, intracellular CO2 and HCO3- accumulation, and photosynthesis in the
      presence but not in the absence of 25 mM Na+. These activities returned to near
      normal levels within 15 min. Transient inhibition was attributed to monensin
      mediated intracellular alkalinization, whereas recovery may have been facilitated
      by cellular mechanisms involved in pH homeostasis or by monensin-mediated H+
      uptake with concomitant K+ efflux. In air-grown cells grown at 200 [mu]M CO2 +
      HCO3- and standing culture cells, Na+-dependent HCO3- transport, intracellular
      HCO3- accumulation, and photosynthesis were also inhibited by monensin, but there
      was little recovery in activity over time. However, normal photosynthetic
      activity could be restored to air-grown cells by the addition of carbonic
      anhydrase, which increased the rate of CO2 supply to the cells. This observation
      indicated that of all the processes required to support photosynthesis only Na+
      dependent HCO3- transport was significantly inhibited by monensin. Monensin
      mediated dissipation of the Na+ chemical gradient between the medium and the
      cells largely accounted for the decline in the HCO3- accumulation ratio from 751
      to 55. The two HCO3- transport systems were further distinguished in that Na+
      dependent HCO3- transport was inhibited by Li+, whereas Na+-independent HCO3-
      transport was not. It is suggested that Na+-dependent HCO3- transport involves an
      Na+/HCO3- symport mechanism that is energized by the Na+ electrochemical
      potential.

PMID- 12232178
TI  - Protein Synthesis and Breakdown during Heat Shock of Cultured Pear (Pyrus
      communis L.) Cells.
AB  - Cultured pear (Pyrus communis L. cv Passe Crassane) cells were subjected to
      temperatures of 39, 42, and 45[deg]C. Heat-shock protein (hsp) synthesis was
      greater at 30[deg]C than at temperatures above 40[deg]C and continued for up to 8
      h. Both cellular uptake of radiolabeled methionine and total protein synthesis
      were progressively lower as the temperature was increased. Polysome levels
      decreased immediately when cells were placed at 39 or 42[deg]C, although at
      39[deg]C the levels began to recover after 1 h. In cells from both temperatures,
      reassembly occurred after transfer of cells to 25[deg]C Four heat-shock-related
      mRNAs[mdash]hsp17, hsp70, and those of two ubiquitin genes[mdash]all showed
      greatest abundance at 39[deg]C and decreased at higher temperatures. Protein
      degradation increased with time at 42 and 45[deg]C, but at 39[deg]C it increased
      for the first 2 h and then decreased. In the presence of cycloheximide, which
      prevented hsp synthesis, protein degradation at 39[deg]C was as great as that at
      45[deg]C in the absence of cycloheximide. The data suggest that hsps may have a
      role in protecting proteins from degradation at the permissive temperature of
      39[deg]C. At temperatures high enough to inhibit hsp synthesis, protein
      degradation was enhanced. Although ubiquitin may play a role in specific protein
      degradation, it does not appear to be involved in increased protein degradation
      occurring above 40[deg]C.

PMID- 12232179
TI  - The Role of Ascorbate Free Radical as an Electron Acceptor to Cytochrome b
      Mediated Trans-Plasma Membrane Electron Transport in Higher Plants.
AB  - The action of ascorbate free radical as an electron acceptor to cytochrome b
      mediated trans-plasma membrane electron transport is demonstrated. Addition of
      ascorbate free radical to ascorbate-loaded plasma membrane vesicles caused a
      rapid oxidation of the cytochrome, followed by a slower re-reduction. The fully
      reduced dehydroascorbate was ineffective.

PMID- 12232180
TI  - In Vitro Cellulose Synthesis in Plants.

PMID- 12232181
TI  - N Demand and the Regulation of Nitrate Uptake.

PMID- 12232182
TI  - Molecular Modeling Indicates that Two Chemically Distinct Classes of Anti-Mitotic
      Herbicide Bind to the Same Receptor Site(s).
AB  - Dinitroaniline and phosphorothioamidate herbicides disrupt microtubule assembly
      from tubulin protein dimers and thereby halt microtubule-based processes such as
      mitosis in plant cells. Despite the contrasting chemical properties of
      dinitroaniline and phosphorothioamidate herbicides, a three-dimensional molecular
      analysis revealed remarkable electrostatic similarity between these two classes
      of herbicide. From these data it is proposed that dinitroaniline and
      phosphorothioamidate herbicides share common binding site(s) in the plant cell.

PMID- 12232183
TI  - Nonvascular, Symplasmic Diffusion of Sucrose Cannot Satisfy the Carbon Demands of
      Growth in the Primary Root Tip of Zea mays L.
AB  - Nonvascular, symplasmic transport of sucrose (Suc) was investigated theoretically
      in the primary root tip of maize (Zea mays L. cv WF9 x Mo 17) seedlings.
      Symplasmic diffusion has been assumed to be the mechanism of transport of Suc to
      cells in the root apical meristem (R.T. Giaquinta, W. Lin, N.L. Sadler, V.R.
      Franceschi [1983] Plant Physiol 72: 362-367), which grow apical to the end of the
      phloem and must build all biomass with carbon supplied from the shoot or kernel.
      We derived an expression for the growth-sustaining Suc flux, which is the minimum
      longitudinal flux that would be required to meet the carbon demands of growth in
      the root apical meristem. We calculated this flux from data on root growth
      velocity, area, and biomass density, taking into account construction and
      maintenance respiration and the production of mucilage by the root cap. We then
      calculated the conductivity of the symplasmic pathway for diffusion, from
      anatomical data on cellular dimensions and the frequency and dimensions of
      plasmodesmata, and from two estimates of the diffusive conductance of a
      plasmodesma, derived from independent data. Then, the concentration gradients
      required to drive a growth-sustaining Suc flux by diffusion alone were calculated
      but were found not to be physiologically reasonable. We also calculated the
      hydraulic conductivity of the plasmodesmatal pathway and found that mass flow of
      Suc solution through plasmodesmata would also be insufficient, by itself, to
      satisfy the carbon demands of growth. However, much of the demand for water to
      cause cell expansion could be met by the water unloaded from the phloem while
      unloading Suc to satisfy the carbon demands of growth, and the hydraulic
      conductivity of plasmodesmata is high enough that much of that water could move
      symplasmically. Either our current understanding of plasmodesmatal ultrastructure
      and function is flawed, or alternative transport mechanisms must exist for Suc
      transport to the meristem.

PMID- 12232184
TI  - The Phosphate Transporter from Pea Mitochondria (Isolation and Characterization
      in Proteolipid Vesicles).
AB  - The phosphate transporter from mitochondria will exchange matrix phosphate for
      cytosolic phosphate and facilitate either phosphate/proton symport or
      phosphate/hydroxyl ion antiport. The phosphate transported into the matrix by
      this carrier is either used for ATP synthesis or exchanges back out to the
      cytosol on the dicarboxylate transporter, permitting entry of malate and
      succinate into the matrix. The phosphate transporter was solubilized from
      etiolated pea (Pisum sativum L. cv Alaska) mitochondrial membranes with Triton X
      114, purified approximately 500-fold by hydroxylapatite chromatography, and
      reconstituted into azolectin vesicles that were preloaded with 0.1 or 10 mM
      phosphate. Phosphate transport was measured as the exchange of preloaded
      phosphate for external [32P]phosphate. Phosphate/phosphate exchange occurred for
      over 40 min at room temperature with an apparent K0.5 of 1.6 mM and a maximum
      velocity of over 700 nmol (mg protein)-1 min-1. Diethyl pyrocarbonate was used as
      an inhibitor-stop reagent. Transport was inhibited by p-hydroxyphenylglyoxal, p
      hydroxymercuribenzoate, pyridoxal 5-phosphate, and dansyl chloride but was
      insensitive to sulfate, nitrate, and N-ethylmaleimide, the standard inhibitor for
      the mammalian phosphate transporter. Phosphate/hydroxyl exchange was stimulated
      when the proton gradient was collapsed with carbonyl cyanide m
      chlorophenylhydrazone, but phosphate/phosphate exchange was unaffected by the
      uncoupler.

PMID- 12232185
TI  - The Response of Maize Seedlings of Different Ages to Hypoxic and Anoxic Stress
      (Changes in Induction of Adh1 mRNA, ADH Activity, and Survival of Anoxia).
AB  - Previously we showed that there is only a transient induction of alcohol
      dehydrogenase 1 (Adh1) transcripts and only a small induction of alcohol
      dehydrogenase (ADH) enzyme activity in root tips of maize (Zea mays L.) seedlings
      subjected to strict anaerobiosis without prior acclimation by exposure to low O2
      (D.L. Andrews, B.G. Cobb, J.R. Johnson, M.C. Drew [1993] Plant Physiol 101: 403
      414). Acclimation of root tips of seedlings by low O2 before anoxia appeared to
      be necessary for full induction of ADH. Here we have examined the effect of
      seedling age on changes in the protein content, induction of Adh1 transcripts,
      and ADH enzyme activity in 5-mm root tips, root axes, and shoots of maize (cv
      TX5855). Their ability to survive anoxia was also recorded. Some seedlings were
      sparged with 4% O2 for 6 or 18 h (a hypoxic pretreatment) followed by anoxia
      (sparged with N2) for up to 48 h. Other seedlings were not acclimated before
      anoxia. In general, younger seedlings had higher initial (aerobic) levels of
      total protein, Adh1 transcripts, and ADH activity than did seedlings that were 2
      d older. For younger seedlings, anoxia alone induced Adh1 transcripts, which
      reached a peak within 6 to 12 h, whereas ADH activity increased throughout the 48
      h treatment. For older seedlings, anoxia caused only a small, transient induction
      of Adh1 transcripts or ADH activity. For seedlings of either age, hypoxia induced
      Adh1 transcripts and ADH activity, both of which were increased further by
      subsequent anoxia in the younger seedlings but to a lesser extent in the older
      seedlings. Despite differences in ADH activity, roots of seedlings of either age
      showed a similar resistance to anoxia. Thus, acclimation of maize seedlings to
      survive anoxia does not appear to be related to induction of high levels of ADH
      activity.

PMID- 12232186
TI  - Hypoxic Induction of Anoxia Tolerance in Roots of Adh1 Null Zea mays L.
AB  - Seedlings of alcohol dehydrogenase 1 null mutants (Adh1-) of Zea mays L., which
      fail to synthesize alcohol dehydrogenase 1 (ADH1) isozymes, were hypoxically
      acclimated by 18 h of exposure to an atmosphere of 4% (v/v) O2 in N2 at 25[deg]C.
      Their ability to tolerate subsequent anoxia by exposure to anaerobic (O2-free)
      conditions was compared with that of unacclimated seedlings that were transferred
      immediately from an atmosphere of 40% (v/v) O2 to anaerobic conditions. Only 10%
      of the root tips of unacclimated seminal roots survived 6 h of anoxia, whereas
      70% of the hypoxically acclimated root tips were viable at 24 h. During anoxia,
      acclimated root tips had enhanced ADH activity compared with unacclimated root
      tips, through induction of Adh2. Despite this, enzyme activity was still only
      about 5% that of acclimated, wild-type root tips and about half that of
      unacclimated, wild-type root tips. During anoxia, acclimated Adh1- root tips
      showed a higher rate of anaerobic respiration and ethanol production, greater
      concentrations of ATP and total adenylates, and a greater adenylate energy charge
      compared with unacclimated root tips. These results suggest that although
      enhanced ADH activity may have raised fermentation rates in acclimated Adh1-
      tissues and thereby contributed to energy metabolism and viability, the high
      levels of ADH activity inducible in acclimated, wild-type maize root tips appear
      to be in excess of that required to increase rates of fermentation.

PMID- 12232187
TI  - Wheat DNA Primase (RNA Primer Synthesis in Vitro, Structural Studies by
      Photochemical Cross-Linking, and Modulation of Primase Activity by DNA
      Polymerases).
AB  - DNA primase synthesizes short RNA primers used by DNA polymerases to initiate DNA
      synthesis. Two proteins of approximately 60 and 50 kD were recognized by specific
      antibodies raised against yeast primase subunits, suggesting a high degree of
      analogy between wheat and yeast primase subunits. Gel-filtration chromatography
      of wheat primase showed two active forms of 60 and 110 to 120 kD. Ultraviolet
      induced cross-linking with radioactive oligothymidilate revealed a highly labeled
      protein of 60 kD. After limited trypsin digestion of wheat (Triticum aestivum L.)
      primase, a major band of 48 kD and two minor bands of 38 and 17 kD were observed.
      In the absence of DNA polymerases, the purified primase synthesizes long RNA
      products. The size of the RNA product synthesized by wheat primase is
      considerably reduced by the presence of DNA polymerases, suggesting a modulatory
      effect of the association between these two enzymes. Lowering the primase
      concentration in the assay also favored short RNA primer synthesis. Several
      properties of the wheat DNA primase using oligoadenylate [oligo(rA)]-primed or
      unprimed polythymidilate templates were studied. The ability of wheat primase,
      without DNA polymerases, to elongate an oligo(rA) primer to long RNA products
      depends on the primer size, temperature, and the divalent cation concentration.
      Thus, Mn2+ ions led to long RNA products in a very wide range of concentrations,
      whereas with Mg2+ long products were observed around 15 mM. We studied the
      ability of purified wheat DNA polymerases to initiate DNA synthesis from an RNA
      primer: wheat DNA polymerase A showed the highest activity, followed by DNA
      polymerases B and CII, whereas DNA polymerase CI was unable to initiate DNA
      synthesis from an RNA primer. Results are discussed in terms of understanding the
      role of these polymerases in DNA replication in plants.

PMID- 12232188
TI  - Agrobacterium-Mediated Transformation of Subterranean Clover (Trifolium
      subterraneum L.).
AB  - We have developed a rapid and reproducible transformation system for subterranean
      clover (Trifolium subterraneum L.) using Agrobacterium tumefaciens-mediated gene
      delivery. Hypocotyl segments from seeds that had been allowed to imbibe were used
      as explants, and regeneration was achieved via organogenesis. Glucose and
      acetosyringone were required in the co-cultivation medium for efficient gene
      transfer. DNA constructs containing four genes encoding the enzymes
      phosphinothricin acetyl transferase, [beta]-glucuronidase (GUS), neomycin
      phosphotransferase, and an [alpha]-amylase inhibitor were used to transform
      subterranean clover. Transgenic shoots were selected on a medium containing 50
      mg/L of phosphinothricin. Four commercial cultivars of subterranean clover
      (representing all three subspecies) have been successfully transformed. Southern
      analysis revealed the integration of T-DNA into the subterranean clover genome.
      The expression of the introduced genes has been confirmed by enzyme assays and
      northern blot analyses. Transformed plants grown in the glasshouse showed
      resistance to the herbicide Basta at applications equal to or higher than rates
      recommended for killing subterranean clover in field conditions. In plants grown
      from the selfed seeds of the primary transformants, the newly acquired gene
      encoding GUS segregated as a dominant Mendelian trait.

PMID- 12232189
TI  - Pretreatment of Parsley (Petroselinum crispum L.) Suspension Cultures with Methyl
      Jasmonate Enhances Elicitation of Activated Oxygen Species.
AB  - Suspension-cultured cells of parsley (Petroselinum crispum L.) were used to
      demonstrate an influence of jasmonic acid methyl ester (JAME) on the elicitation
      of activated oxygen species. Preincubation of the cell cultures for 1 d with JAME
      greatly enhanced the subsequent induction by an elicitor preparation from cell
      walls of Phytophtora megasperma f. sp. glycinea (Pmg elicitor) and by the
      polycation chitosan. Shorter preincubation times with JAME were less efficient,
      and the effect was saturated at about 5 [mu]M JAME. Treatment of the crude Pmg
      elicitor with trypsin abolished induction of activated oxygen species, an effect
      similar to that seen with elicitation of coumarin secretion. These results
      suggest that JAME conditioned the parsley suspension cells in a time-dependent
      manner to become more responsive to elicitation, reminiscent of developmental
      effects caused by JAME in whole plants. It is interesting that pretreatment of
      the parsley cultures with 2,6-dichloroisonicotinic and 5-chlorosalicylic acid
      only slightly enhanced the elicitation of activated oxygen species, whereas these
      substances greatly enhanced the elicitation of coumarin secretion. Therefore,
      these presumed inducers of systemic acquired resistance exhibit a specificity
      different from JAME.

PMID- 12232190
TI  - Starch Phosphorylation in Potato Tubers Proceeds Concurrently with de Novo
      Biosynthesis of Starch.
AB  - The in vivo phosphorylation of starch was studied in Solanum tuberosum cv
      Dianella and Posmo. Small starch granules contain 25% more ester-bound phosphate
      per glucose residue than large starch granules. The degree of phosphorylation was
      found to be almost constant during tuber development. Isolated tuber discs
      synthesize starch from externally supplied glucose at a significant rate. Tuber
      discs supplied with glucose and [32P]orthophosphate incorporate radiolabeled
      phosphorus into the starch. The level of 32P incorporation is proportional to the
      amount of starch synthesized. The incorporation of 32P from orthophosphate is
      correlated to de novo synthesis of starch, since the incorporation of 32P is
      diminished upon inhibition of starch synthesis by fluoride. Based on the amount
      of [14C]glucose phosphate isolated after hydrolysis of purified starch from tuber
      discs incubated in the presence of [U-14C]glucose, approximately 0.5% of the
      glucose residues of the de novo-synthesized starch are phosphorylated. This value
      is in general agreement with the observed levels of phosphorus in starch
      accumulated during tuber development. Thus, the enzyme system responsible for
      starch phosphorylation is fully active in the isolated tuber discs, and the
      starch phosphorylation proceeds as an integrated part of de novo starch
      synthesis.

PMID- 12232191
TI  - 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Activity in the Endosperm of
      Maize vivipary Mutants.
AB  - During seed maturation the levels of the rate-limiting enzyme of isoprenoid
      biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) decrease
      while the levels of the isoprenoid compund abscisic acid (ABA) increase. In the
      present study, we demonstrate that HMGR specific activity is inversely correlated
      with endogenous ABA levels in Zea mays endosperm during seed development. HMGR
      specific activity and ABA levels were measured in the endosperm of the maize
      vivipary mutuants vp2, vp5, and vp7, which are defective in ABA biosynthesis, and
      vp1, which is defective in an ABA response element. Reduced ABA levels were
      observed in the endosperm of vp2, vp5, and vp7, whereas HMGR activity levels were
      higher compared with wild-type sibling endosperm activity. HMGR activities were
      increased by as much as 37% (vp2), 45% (vp5), and 58% (vp7) in the mutants.
      Endosperm HMGR activity in the vp1 mutant was also increased (41%) relative to
      wild-type siblings, even though vp1 does not have reduced ABA levels. In
      addition, exogenous ABA inhibits HMGR activity 34 to 50% in maize roots. These
      results sugggest the HMGR activity levels during seed development are regulated
      via a Vp1-dependent signal transduction pathway that is affected by the reduced
      ABA content of vp2, vp5, and vp7 endosperm.

PMID- 12232192
TI  - Ethylene-Induced Increase in Glutamine Synthetase Activity and mRNA Levels in
      Hevea brasiliensis Latex Cells.
AB  - Ethylene, used as a stimulant of latex production in Hevea brasiliensis,
      significantly activates the regenerating metabolism within the laticiferous
      cells. In this context, attention was focused on glutamine synthetase (GS; EC
      6.3.1.2), a key enzyme in nitrogen metabolism. A specific and significant
      activation of the cytosolic glutamine synthetase (GScyt) in the laticiferous
      cells after ethylene treatment parallels the increase of latex yield. A marked
      accumulation of the corresponding mRNA was found, but in contrast, a slight and
      variable increase of the polypeptide level is at the limit of detection by
      western blotting. The GS response to ethylene might be mediated by ammonia that
      increases in latex cytosol following ethylene treatment. The physiological
      significance for such a regulation by ethylene of the GScyt is discussed in terms
      of the nitrogen requirement for protein synthesis associated with latex
      regeneration.

PMID- 12232193
TI  - Identification of Intracellular Carbonic Anhydrase in Chlamydomonas reinhardtii
      with a Carbonic Anhydrase-Directed Photoaffinity Label.
AB  - A carbonic anhydrase (CA)-directed photoaffinity reagent, 125I-labeled p
      aminomethylbenzenesulfonamide-4-azidosalicylamide,was synthesized and shown to
      derivatize periplasmic CA in the unicellular green alga Chlamydomonas
      reinhardtii. The photoderivatization of purified C. reinhardtii periplasmic CA or
      intact C. reinhardtii cells with the reagent resulted in the modification of the
      large (37 kD) subunit of the enzyme. Photoderivatization of proteins in lysed C.
      reinhardtii cells also resulted in the specific labeling of a polypeptide of 30
      kD. Centrifugation of the cell extract prior to photoaffinity labeling revealed
      that the labeled peptide was present predominantly in a particulate fraction. The
      photoaffinity-labeled 30-kD polypeptide was not observed in extracts from a
      mutant of C. reinhardtii that is believed to be deficient in an intracellular
      form of CA. These results provide evidence that the 30-kD polypeptide, which is
      photoaffinity labeled in lysed C. reinhardtii cells, is an intracellular form of
      CA.

PMID- 12232194
TI  - Photoresponses of Light-Grown phyA Mutants of Arabidopsis (Phytochrome A Is
      Required for the Perception of Daylength Extensions).
AB  - Several aspects of the photophysiology of wild-type Arabidopsis thaliana
      seedlings were compared with those of a phytochrome A null mutant, phyA-1, and a
      mutant, fhy1, that is putatively involved in the transduction of light signals
      from phytochrome A. Although phyA seedlings display a near wild-type phenotype
      when grown in white light (W), they nevertheless display several photomorphogenic
      abnormalities. Thus, whereas the germination of wild-type and fhy1 seeds is
      almost fully promoted by a pulse of red light (R) or by continuous far-red light
      (FR), phyA seed germination is responsive only to R. Following growth under
      day/night cycles, but not under continuous W, the hypocotyls of light-grown phyA
      and fhy1 seedlings are more elongated than those of wild-type seedlings. For
      seedlings grown under low red/far-red (R/FR) ratio light conditions, phyA and
      fhy1 seedlings display a more marked promotion of hypocotyl elongation than wild
      type seedlings. Similarly, seedlings that are doubly null for phytochrome A and
      phytochrome B(phyA phyB) also have more elongated hypocotyls under low R/FR ratio
      conditions than phyB seedlings. This indicates that phytochrome A action in light
      grown seedlings is antagonistic to the action of phytochrome B. Although wild
      type, fhy1, and phyA seedlings flower at essentially the same time under both
      short-day and long-day conditions, an obvious consequence of phytochrome A
      deficiency is a pronounced late flowering under conditions where a short day of 8
      h of fluorescent W is extended by 8 h of low-fluence-rate incandescent light. The
      evidence thus indicates that phytochrome A plays a role in seed germination, in
      the control of elongation growth of light-grown seedlings, and in the perception
      of daylength.

PMID- 12232195
TI  - The Metabolites of the Herbicide L-Phosphinothricin (Glufosinate)
      (Identification, Stability, and Mobility in Transgenic, Herbicide-Resistant, and
      Untransformed Plants).
AB  - The metabolism of the herbicide L-phosphinothricin (L-Pt) was analyzed in tobacco
      (Nicotiana tabacum), alfalfa (Medicago sativa), and carrot (Daucus carota). In
      transgenic, Pt-resistant plants expressing the Pt-N-acetyltransferase gene (pat),
      L-Pt was acetylated, resulting in two forms of N-acetyl-Pt (ac-Pt). In transgenic
      plants expressing only low pat-encoded acetylating activity as well as in
      genetically unmodified plants, three metabolic compounds 4-methylphosphinico-2
      oxo-butanoic acid, 3-methylphosphinico-propanoic acid (MPP), and 4
      methylphosphinico-2-hydroxy-butanoic acid (MHB) were identified. Hence, the
      transgene-encoded acetylation of L-Pt competes with a plant-specific degradation.
      The compounds MPP, MHB, and ac-Pt were found to be the final, stable products of
      the plant's metabolic pathways. The mobility of these stable compounds in the
      plant was investigated: L-Pt as well as the derived metabolites were found to be
      preferentially transported to the upper regions of the plant.

PMID- 12232196
TI  - Comparison of Methods to Estimate Dark Respiration in the Light in Leaves of Two
      Woody Species.
AB  - Dark respiration in the light was estimated in leaves of two woody species
      (Heteromeles arbutifolia Ait. and Lepechinia fragans Greene) using two different
      approaches based on gas-exchange techniques: the Kok method and the Laisk method.
      In all cases, dark respiration in the light was lower (P < 0.05) than respiration
      in darkness, indicating that dark respiration was inhibited in the light. Rates
      of dark respiration in the light estimated by the Laisk method were 52% higher (P
      < 0.05) than those estimated by the Kok method. Differences between the methods
      could be explained by the low ambient CO2 concentrations required by the Laisk
      approach. The mean value of the inhibition of respiration by light for the two
      species, corrected for the ambient CO2 concentration effect, was 55%. Despite the
      differences in leaf characteristics between the species, values of the CO2
      photocompensation point, at which the rate of photosynthetic CO2 uptake equaled
      that of photorespiratory CO2 evolution, were very constant, suggesting an
      excellent consistency in the results obtained with the Laisk approach.

PMID- 12232197
TI  - Responses of Ribulose-1,5-Bisphosphate Carboxylase, Cytochrome f, and Sucrose
      Synthesis Enzymes in Rice Leaves to Leaf Nitrogen and Their Relationships to
      Photosynthesis.
AB  - The photosynthetic gas-exchange rates and various biochemical components of
      photosynthesis, including ribulose-1,5-bisphosphate carboxylase (Rubisco)
      content, cytochrome (Cyt) f content, and the activities of two sucrose synthesis
      enzymes, were examined in young, fully expanded leaves of rice (Oryza sativa L.)
      grown hydroponically in different nitrogen concentrations. The light-saturated
      rate of photosynthesis at an intercellular CO2 pressure of 20 Pa (CO2-limited
      photosynthesis) was linearly dependent on leaf nitrogen content, but
      curvilinearly correlated with Rubisco content. This difference was due to a
      greater than proportional increase in Rubisco content relative to leaf nitrogen
      content and the presence of a CO2 transfer resistance between the intercellular
      air spaces and the carboxylation sites. CO2-limited photosynthesis was
      proportional to Cyt f content, one of the key components of electron transport,
      but was not proportional to the activities of cytosolic fructose-1,6
      bisphosphatase and sucrose phosphate synthase, the two regulatory enzymes of
      sucrose synthesis. Light-saturated photosynthesis above an intercellular CO2
      pressure of 60 Pa (CO2-saturated photosynthesis) was curvilinearly dependent on
      leaf nitrogen content. This CO2-saturated photosynthesis was proportional to Cyt
      f content in the low- and normal-nitrogen leaves, and correlated better with the
      activities of cytosolic fructose-1,6-bisphosphatase and sucrose phosphate
      synthase in the high-nitrogen leaves. The increase in the activities of these two
      enzymes with increasing leaf nitrogen was not as great as the increase in Cyt f
      content. Thus, as leaf nitrogen increased, the limitation caused by the
      activities of sucrose synthesis enzymes came into play, which resulted in the
      curvilinear relationship. However, this limitation by sucrose synthesis enzymes
      did not affect photosynthesis under normal ambient air.

PMID- 12232198
TI  - Nitrogen Use within the Growing Leaf Blade of Tall Fescue.
AB  - Leaf elongation rate (LER) of grasses depends on N supply and is expressed mostly
      through cell production, whereas most N in mature leaf tissues is chloroplastic.
      Our objective was to evaluate a possible competition for N between cell
      production and chloroplast development processes, utilizing the gradient of cell
      development along the leaf growth zone of tall fescue (Festuca arundinacea
      Schreb.). Under the two contrasting N regimes, total N content was highest in the
      cell production zone, declined sharply as cells elongated, and remained
      relatively constant in more distal positions, at values close to those measured
      in mature tissues. A similar pattern was found for N in proteins and nucleic
      acids that were not soluble in 80% ethanol. Content of N compounds soluble in 80%
      ethanol was higher in the cell production and elongation zones than in mature
      parts of the leaf. NO3- N content was low in the cell production zone and
      increased in the cell elongation zone for high-N plants. The deposition rate of
      total N in the growth zone was much higher with plants in high N than in those
      shifted to no N. For both N regimes, most N was deposited during cell production
      and early cell elongation. Little N was deposited during cell maturation where
      ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) was being actively
      synthesized. This suggests that synthesis of Rubisco, and probably other
      chloroplastic proteins, occurs largely from recycling of N that was previously
      incorporated into proteins during cell production. Thus, Rubisco content in
      mature tissues is more closely associated with N deposited during cell production
      than with N deposited during its biosynthesis.

PMID- 12232199
TI  - Pectin Methylesterase Isoforms in Tomato (Lycopersicon esculentum) Tissues
      (Effects of Expression of a Pectin Methylesterase Antisense Gene).
AB  - We have identified two major groups of pectin methylesterase (PME, EC 3.1.1.11)
      isoforms in various tissues of tomatoes (Lycopersicon esculentum). These two
      groups exhibited differential immuno-cross-reactivity with polyclonal antibodies
      raised against tomato fruit PME or flax callus PME and differences in their
      accumulation patterns in tissues of wild-type and transgenic tomato plants
      expressing a PME antisense gene. The group I isoforms with isoelectric points
      (pls) of 8.2, 8.4, and 8.5 are specific to fruit tissue, where they are the major
      forms of PME activity. The group II PME isoforms, with pl values of 9 and above,
      are observed in both vegetative and fruit tissues. The group I isoforms cross
      react with polyclonal antibodies raised to a PME isoform purified from fruit,
      whereas the group II isoforms cross-react with antibodies to a PME purified from
      flax callus. Expression of a fruit-specific PME anti-sense gene impairs
      accumulation of the group I PME isoforms, with no apparent effect on the
      accumulation of the group II PME isoforms. The absence of any noticeable effects
      on growth and development of transgenic plants suggests that the group I PME
      isoforms are not involved in plant growth and development and may play a role
      under special circumstances such as cell separation during fruit ripening.

PMID- 12232200
TI  - Phosphorylation of a Renatured Protein from Etiolated Wheat Leaf Protoplasts Is
      Modulated by Blue and Red Light.
AB  - Red-light irradiation of etiolated wheat (Triticum aestivum L.) leaf protoplasts
      rapidly increases calcium-dependent phosphorylation in vivo of 70- and 60-kD
      peptides, and the phosphorylation is attenuated by simultaneous far-red light
      (K.M. Fallon, P.S. Shacklock, A.J. Trewavas [1993] Plant Physiology 101:1039
      1045). When these protoplasts were solubilized in sodium dodecyl sulfate and
      protein kinase was renatured in situ after gel electrophoresis, a single 60-kD
      protein kinase was detected. In situ phosphorylation was inhibited by prior
      exposure of etiolated protoplasts to 30 to 60 s of white, 1 to 2 min of blue, or
      2 to 5 min of red light. The effect of red light was attenuated by concomitant
      far-red light. The inhibition of in situ phosphorylation by light was lost after
      a further prolonged incubation of protoplasts in darkness. In situ
      phosphorylation was calcium dependent, and the electrophoretic mobility of the
      protein kinase was increased in the presence of calcium ions. Although treatment
      of protoplasts with ionophores and channel blockers produced data consistent with
      in vivo regulation of phosphorylation by cytosol calcium, additional light
      activated transduction pathways have to be invoked to explain all the
      observations.

PMID- 12232201
TI  - Isoprene Emission from Velvet Bean Leaves (Interactions among Nitrogen
      Availability, Growth Photon Flux Density, and Leaf Development).
AB  - Although isoprene synthesis is closely coupled to photosynthesis, both via ATP
      requirements and carbon substrate availability, control of isoprene emission is
      not always closely linked to photosynthetic processes. In this study we grew
      velvet bean (Mucuna sp.) under different levels of photon flux density (PFD) and
      nitrogen availability in an effort to understand better the degree to which these
      two processes are linked. As has been observed in past studies, we found that
      during early leaf ontogeny the onset of positive rates of net photosynthesis
      precedes that of isoprene emission by 3 to 4 d. Other studies have shown that
      this lag is correlated with the induction of isoprene synthase activity,
      indicating that overall control of the process is under control of that enzyme.
      During leaf senescence, photosynthesis rate and isoprene emission rate declined
      in parallel, suggesting similar controls over the two processes. This coordinated
      decline was accelerated when plants were grown with high PFD and high nitrogen
      availability. The latter effect included declines in the photon yield of
      photosynthesis, suggesting that an unexplained stress arose during growth under
      these conditions, triggering a premature decline in photosynthesis and isoprene
      emission rate. In mature leaves, growth PFD and nitrogen nutrition affected
      photosynthesis and isoprene emission in qualitatively similar, but quantitatively
      different, ways. This resulted in a significant shift in the percentage of fixed
      carbon that was re-emitted as isoprene. In the case of increasing growth PFD,
      isoprene emission rate was more strongly affected than photosynthesis rate, and
      more carbon was lost as isoprene. In the case of increasing nitrogen,
      photosynthesis rate increased more than isoprene emission rate, and leaves
      containing high amounts of nitrogen lost a lower percentage of their assimilated
      carbon as isoprene. Taken together, our results demonstrate that, although the
      general correlation between isoprene emission rate and photosynthesis rate is
      consistently expressed, there is evidence that both processes are capable of
      independent responses to plant growth environment.

PMID- 12232202
TI  - Acclimation of the Photosynthetic Apparatus to Growth Irradiance in a Mutant
      Strain of Synechococcus Lacking Iron Superoxide Dismutase.
AB  - The acclimation of the photosynthetic apparatus to growth irradiance in a mutant
      strain of Synechococcus sp. PCC 7942 lacking detectable iron superoxide dismutase
      activity was studied. The growth of the mutant was inhibited at concentrations of
      methyl viologen 4 orders of magnitude smaller than those required to inhibit the
      growth of the wild-type strain. An increased sensitivity of photosynthetic
      electron transport near photosystem I (PSI) toward photooxidative stress was also
      observed in the mutant strain. In the absence of methyl viologen, the mutant
      exhibited similar growth rates compared with those of the wild type, even at high
      growth irradiance (350 [mu]E m-2 s-1) where chronic inhibition of photosystem II
      (PSII) was observed in both strains. Under high growth irradiance, the ratios of
      PSII to PSI and of [alpha]-phycocyanin to chlorophyll a were less than one-third
      of the values for the wild type. In both strains, cellular contents of
      chlorophyll a, [alpha]-phycocyanin, and [beta]-carotene, as well as the length of
      the phycobilisome rods, declined with increasing growth irradiance. Only the
      cellular content of the carotenoid zeaxanthin seemed to be independent of growth
      irradiance. These results suggest an altered acclimation to growth irradiance in
      the sodB mutant in which the stoichiometry between PSI and PSII is adjusted to
      compensate for the loss of PSI efficiency occurring under high growth irradiance.
      Similar shortening of the phycobilisome rods in the sodB mutant and wild-type
      strain suggest that phycobilisome rod length is regulated independently of
      photosystem stoichiometry.

PMID- 12232203
TI  - Chilling Injury Induces Lipid Phase Changes in Membranes of Tomato Fruit.
AB  - Wide-angle x-ray diffraction has provided evidence for lipid phase separations in
      microsomal membranes from chill-injured tomato (Lycopersicon esculentum Mill. cv
      Caruso) fruit. Mature-green fruit stored for 20 d at 5[deg]C had not begun to
      ripen and were essentially free of chilling injury symptoms. Within 4 d of being
      returned to 25[deg]C, however, the fruit displayed characteristic symptoms of
      chilling injury, including translucent water-soaked patches, surface pitting, and
      irregular pigmentation. Membrane damage measured as electrolyte leakage from
      pericarp discs intensified after the fruit were returned to ambient temperature.
      Wide-angle x-ray diffraction patterns recorded at 25[deg]C for microsomal
      membranes isolated from untreated, mature-green fruit indicated that the membrane
      bilayers were exclusively liquid-crystalline. Diffraction patterns for microsomal
      membranes from fruit stored for 20 d at 5[deg]C showed only trace amounts of gel
      phase lipid, but within 4 d of subsequent exposure of the fruit to ambient
      temperature, there was evidence for a pronounced lateral phase separation of
      lipids within the membranes that would render them leaky. Inas-much as the phase
      separations were detectable at 25[deg]C and became pronounced only subsequent to
      the chilling episode, they appear to be an indirect rather than direct effect of
      exposure to low temperature. The diffraction data thus support the notion that
      the lipid phase changes observed here are not directly induced by low temperature
      but rather reflect subsequent biochemical changes in the bilayers that may
      contribute to the development of chilling symptoms.

PMID- 12232204
TI  - Competitive Inhibition of High-Affinity Oryzalin Binding to Plant Tubulin by the
      Phosphoric Amide Herbicide Amiprophos-Methyl.
AB  - Amiprophos-methyl (APM), a phosphoric amide herbicide, was previously reported to
      inhibit the in vitro polymerization of isolated plant tubulin (L.C. Morejohn,
      D.E. Fosket [1984] Science 224: 874-876), yet little other biochemical
      information exists concerning this compound. To characterize further the
      mechanism of action of APM, its interactions with tubulin and microtubules
      purified from cultured cells of tobacco (Nicotiana tabacum cv Bright Yellow-2)
      were investigated. Low micromolar concentrations of APM depolymerized preformed,
      taxol-stabilized tobacco microtubules. Remarkably, at the lowest APM
      concentration examined, many short microtubules were redistributed into fewer but
      2.7-fold longer microtubules without a substantial decrease in total polymer
      mass, a result consistent with an end-to-end annealing of microtubules with
      enhanced kinetic properties. Quasi-equilibrium binding measurements showed that
      tobacco tubulin binds [14C]oryzalin with high affinity to produce a tubulin
      oryzalin complex having a dissociation constant (Kd) = 117 nM (pH 6.9; 23[deg]C).
      Also, an estimated maximum molar binding stoichiometry of 0.32 indicates
      pharamacological heterogeneity of tobacco dimers and may be related to structural
      heterogeneity of tobacco tubulin subunits. APM inhibits competitively the binding
      of [14C]oryzalin to tubulin with an inhibition constant (Ki) = 5 [mu]M,
      indicating the formation of a moderate affinity tubulin-APM complex that may
      interact with the ends of microtubules. APM concentrations inhibiting tobacco
      cell growth were within the threshold range of APM concentrations that
      depolymerized cellular microtubules, indicating that growth inhibition is caused
      by microtubules depolymerization. APM had no apparent effect on microtubules in
      mouse 3T3 fibroblasts. Because cellular microtubules were depolymerized at APM
      and oryzalin concentrations below their respective Ki and Kd values, both
      herbicides are proposed to depolymerize microtubules by a substoichiometric
      endwise mechanism.

PMID- 12232205
TI  - Differential Gene Expression in Chilling-Acclimated Maize Seedlings and Evidence
      for the Involvement of Abscisic Acid in Chilling Tolerance.
AB  - An acclimation phenomenon was characterized in seedlings of chilling-sensitive
      maize (Zea mays L.) inbred G50 (Pioneer). Seedlings were germinated at 27[deg]C
      for 3 d and then exposed to chilling treatments of 4, 5, or 6[deg]C for 2, 4, 7,
      or 10 d in darkness. Damage symptoms in the more severe treatments included a
      waterlogged appearance and a discoloration of the tissue. The symptoms were most
      obvious in the mesocotyl. After a 10-d grow-out period in the greenhouse,
      moderately damaged seedlings exhibited chlorotic areas, an occasional disruption
      in leaf expansion, and a constriction of the mesocotyl. Growth and survival were
      improved by first exposing seedlings to a 14[deg]C acclimation treatment for 3 d
      before applying the chilling treatment. After chilling at 5[deg]C for 7 d, 79% of
      the acclimated seedlings survived, whereas only 22% of the nonacclimated
      seedlings survived. Differences in gene expression between acclimated and control
      seedlings were investigated using subtraction and differential screening
      techniques. Transcripts corresponding to three genes, car333, car30, and car757
      (chilling acclimation responsive), were present in higher levels in seedlings
      after acclimation. Sequence analysis identified car333 as cat3, which encodes
      maize mitochondrial catalase isozyme 3. Characterization of these three clones
      revealed that all corresponding transcripts were elevated in acclimated seedlings
      in a manner that depended on the organ, i.e. coleoptile, mesocotyl, or root.
      Although transcripts were elevated in all three organs in response to
      acclimation, car30 was most abundant in the coleoptile and root, whereas cat3 and
      car757 were most abundant in the coleoptile and mesocotyl. Catalase activity
      followed the same general trend as cat3 transcript levels. Exogenous treatment
      with abscisic acid (ABA) resulted in an improvement in growth and survival of
      nonacclimated, chilled seedlings. Inhibition of ABA biosynthesis with fluridone
      abolished acclimation-induced chilling tolerance, and exogenous application of
      ABA to fluridone-treated seedlings restored chilling tolerance. Exogenous ABA
      treatment also resulted in increases in cat3, car30, and car757 transcript levels
      and catalase activity in the same organ-specific manner as in acclimated
      seedlings. These results indicate that ABA synthesis is essential for chilling
      tolerance. However, measurement of ABA levels in mesocotyls during acclimation
      and chilling revealed only a marginal increase during acclimation and a dramatic
      increase during chilling, regardless of whether or not seedlings were acclimated.
      Thus, although ABA may be required for chilling tolerance, we have no conclusive
      evidence that the acclimation process is mediated by ABA.

PMID- 12232206
TI  - A Role for the Stele in Intertissue Signaling in the Initiation of Abscission in
      Bean Leaves (Phaseolus vulgaris L.).
AB  - A combination of microdissection and viscometric endo-[beta]-1,4-glucanhydrolase
      assays was used to investigate if the early appearance of the abscission-related
      isoelectric point-9.5 endo-[beta]-1,4-glucanhydrolase in the stele of the
      pulvinus and abscission zone of the foliar abscission zone of Phaseolus vulgaris
      L. prior to cell separation (reported by E. del Campillo, P.D. Reid, R. Sexton,
      L.N.Lewis [1990] Plant Cell 2: 245-254) indicates that the vascular tissue of
      this region has a specific role in abscission. We find that no endo-[beta]-1,4
      glucanhydrolase activity or cell separation is detectable in the abscission zone
      cortex if the abscission zone cortex is separated from the stele tissue. If the
      stele is separated from the abscission zone cortex after a lag period but again
      before any endo-[beta]-1,4-glucanhydrolase activity is present in the abscission
      zone cortex, then the enzyme is produced in the cortex and abscission ensues. We
      conclude that the cortex of the abscission zone is able to abscind independently
      of the vascular tissue only after the vascular tissue has begun to respond to
      abscission-promoting signals. We suggest that ethylene promotes formation of an
      abscission-permitting signal in the stele of the abscission zone and pulvinus,
      and that this signal is an essential elicitor for the synthesis of cell
      separation enzymes in the target cells of the abscission zone cortex.

PMID- 12232207
TI  - Regulation of Electron Transport in Photosystems I and II in C3, C3-C4, and C4
      Species of Panicum in Response to Changing Irradiance and O2 Levels.
AB  - Regulation of the quantum yields of linear electron transport and photosystem II
      photochemistry ([phi]II) with changing irradiance and gas-phase O2 concentration
      was studied in leaf tissue from Panicum bisulcatum (C3), Panicum milioides (C3
      C4), and Panicum antidotale (C4) at 200 [mu]bars of CO2 and 25[deg]C using
      infrared gas analysis and chlorophyll fluorescence yield measurements. When the
      O2 level was increased from 14 to 213 mbars at high irradiance, [phi]II increased
      by as much as 115% in P. bisulcatum but by no more than 17% in P. antidotale.
      Under the same conditions [phi]II increased to an intermediate degree in P.
      milioides. Measurements of accumulation of the photooxidized form of the
      photosystem I reaction center (P700+) based on the light-dependent in vivo
      absorbance change at 830 nm indicate that the steady-state concentration of P700+
      varied in an antiparallel manner with [phi]II when either the irradiance or O2
      concentration was changed. Hence, O2-dependent changes in [phi]II were indicative
      of variations in linear photosynthetic electron transport. These experiments
      revealed, however, that a significant capacity was retained for in vivo
      regulation of the apparent quantum yield of photosystem I ([phi]I) independently
      of [phi]II+ Coordinate regulation of quantum yields of photosystems I and II
      (expressed as [phi]I:[phi]II in response to changing irradiance and O2 level
      differed markedly for the C3 and C4 species, and the response for the C3-C4
      species most closely resembled that observed for the C4 species. The fraction of
      total linear electron transport supporting photorespiration at 213 mbars of O2
      was negligible in the C4 species and was 13% lower in the C3-C4 species relative
      to the C3 species as calculated from fluorescence and gas-exchange
      determinations. At high photon-flux rates and high O2 concentration, the
      potential benefit to light use for net CO2 uptake arising from lower
      photorespiration in P. milioides was offset by a reduced capacity for total CO2-
      and O2-dependent noncyclic electron transport in this species compared with P.
      bisulcatum.

PMID- 12232208
TI  - The LOX1 Gene of Arabidopsis Is Temporally and Spatially Regulated in Germinating
      Seedlings.
AB  - We examined the temporal and spatial expression patterns of the LOX1 gene during
      the development of Arabidopsis thaliana seedlings. Measurements of steady-state
      LOX1 mRNA levels indicated that this gene is transiently expressed during
      germination. LOX1 mRNA was not detected in seed that had imbibed (T0) but reached
      a maximum level by 1 d in both light- and dark-grown seedlings. The induction of
      the LOX1 gene was not light dependent; however, mRNA levels were 4-fold greater
      in light-grown seedlings. Immunoblot analysis of lipoxygenase protein levels and
      measurements of enzyme activity suggested that the induction of the LOX1 gene
      resulted in the production of functional lipoxygenase enzyme. Lipoxygenase
      protein was not present in dry seed or seed that had imbibed, but was first
      detected by immunoblot analysis after 1 and 2 d of growth in the light and dark,
      respectively. In both cases, lipoxygenase protein levels remained high for 2 d
      and then declined. Lipoxygenase activity paralleled the changes in protein
      levels. In situ hybridization studies revealed that the LOX1 gene is transiently
      expressed in the epidermis and the aleurone layer during germination. LOX1 mRNA
      levels were particularly high in the epidermis of the radicle and the adaxial
      side of the cotyledons. These results suggest that the LOX1 gene product is
      produced specifically during early germination and plays a role in the
      functioning of the epidermis.

PMID- 12232209
TI  - Isolation and Characterization of S-Adenosyl-L-Methionine:Tetrahydroberberine-cis
      N-Methyltransferase from Suspension Cultures of Sanguinaria canadensis L.
AB  - As part of a continuing study of the induction of alkaloid biosynthesis, we
      report the isolation to homogeneity and characterization of S-adenosyl-L
      methionine:tetrahydroberberine-cis-N-mehtyltransferase from suspension cultures
      of Sanguinaria canadensis that were induced to produce alkaloids by hormone
      depletion. This enzyme catalyzes the stereospecific transfer of a methyl group
      from S-adenosyl-L-methionine to the tertiary nitrogen of the protoberberine
      alkaloid tetrahydroberberine (canadine). The enzyme was purified 315-fold by
      ammonium sulfate precipitation, gel permeation chromatography, affinity dye
      chromatography, and both diethylaminoethyl and Mono-Q ion-exchange
      chromatography. The enzyme was further purified to an optimum specific activity
      of 225 nkat/mg of protein (3500-fold) and electrophoretic homogeneity by native
      polyacrylamide gel electrophoresis (PAGE). In contrast to previous reports with
      partially purified enzyme, the isolated protein was found to have a pH optimum of
      7.0, a temperature optimum of 25 to 30[deg]C, and an isoelectric point of 5.1.
      Furthermore, the molecular weight of the homogeneous protein was found to be
      39,000 by sodium dodecyl sulfate-PAGE. The homogeneous enzyme preferred
      tetrahydroberberine over all other substrates tested, showing an apparent Km of
      2.1 [mu]M, but also showed partial activity with tetrahydrojatrorrhizine and
      tetrahydropalmatrubine.

PMID- 12232210
TI  - Carotenoid Biosynthesis during Tomato Fruit Development (Evidence for Tissue
      Specific Gene Expression).
AB  - Tomato (Lycopersicon esculentum Mill. cv Ailsa Craig) fruit, at five stages of
      development, have been analyzed for their carotenoid and chlorophyll (Chl)
      contents, in vitro activities of phytoene synthase, phytoene desaturase, and
      lycopene cyclase, as well as expression of the phytoene synthase (Psy) and
      phytoene desaturase (Pds) genes. During ripening, the total carotenoids increased
      with a concomitant decrease in Chl. Although the highest carotenoid content
      (consisting mainly of lycopene and [beta]-carotene) was found in ripe fruit, the
      greatest carotenogenic enzymic activities were found in green fruit. Phytoene
      synthase was located in the plastid stroma, whereas the metabolism of phytoene
      was associated with plastid membranes during all stages of fruit development. The
      in vitro products of phytoene desaturation altered from being predominantly
      phytofluence and [zeta]-carotene in chloroplasts to becoming mainly lycopene in
      chromoplasts. The expression of Psy was detected in breaker and ripe fruit, as
      well as flowers, but was not detectable by northern blot analysis in leaves or
      green fruits. The Pds gene transcript was barely detectable in green fruit and
      leaves but was expressed in flowers and breaker fruit. These results suggest that
      transcription of Psy and Pds is regulated developmentally, with expression being
      considerably elevated in chromoplast-containing tissues. Antiserum to the
      Synechococcus phytoene synthase cross-reacted with phytoene synthase of green
      fruit only on western blots and not with the enzyme from ripe fruit. In contrast,
      a monoclonal antibody to the Psy gene product only cross-reacted with phytoene
      synthase from ripe fruit. The enzymes from green and ripe fruit had different
      molecular masses of 42 and 38 kD, respectively. The absence of detectable Psy and
      Pds mRNA in green tissues using northern blot analyses, despite high levels of
      phytoene synthase and desaturase activity, lends support to the hypothesis of
      divergent genes encoding these enzymes.

PMID- 12232211
TI  - A Metabolic Control Analysis of the Glutamine Synthetase/Glutamate Synthase Cycle
      in Isolated Barley (Hordeum vulgare L.) Chloroplasts.
AB  - Ammonia assimilation in chloroplasts occurs via the glutamine
      synthetase/glutamate synthase (GS/GOGAT) cycle. To determine the extent to which
      these enzymes contribute to the control of ammonia assimilation, a metabolic
      control analysis was performed on isolated barley (Hordeum vulgare L.) leaf
      chloroplasts. Pathway flux was measured polarographically as ammonium-plus-2
      oxoglutarate-plus-glutamine-dependent O2 evolution in illuminated chloroplasts.
      Enzyme activity was modulated by titration with specific, irreversible inhibitors
      of GS (phosphinothricin) and GOGAT (azaserine). Flux control coefficients (CJ0E0)
      were determined (a) by differentiation of best-fit hyperbolic curves of the data
      sets (flux versus enzyme activity), and (b) from estimates of the deviation
      indices (D/[prime]E0). Both analyses gave similar values for the coefficients.
      The control coefficient for GS was relatively high and the value did not change
      significantly with changes in 2-oxoglutarate concentration (C/0E0 = 0.58 at 5 mM
      2-oxoglutarate and 0.40 at 20 mM 2-oxoglutarate). The control coefficient for
      GOGAT decreased with decreasing glutamine concentrations, from 0.76 at 20 mM
      glutamine to 0.19 at 10 mM glutamine. Thus, at high concentrations of glutamine,
      GOGAT exerts a major control over flux with a significant contribution also from
      GS. At lower concentrations of glutamine, however, GOGAT exerts far less control
      over pathway flux.

PMID- 12232212
TI  - Immunopurification and Immunocharacterization of the Glucosinolate Biosynthetic
      Enzyme Thiohydroximate S-Glucosyltransferase.
AB  - Preparing homogeneous UDP-glucose:thiohydroximate S-glucosyltransferase (S-GT),
      the penultimate biosynthetic enzyme of glucosinolates, by standard
      chromatographic methods has yielded too little protein for adequate purity
      evaluation, identity verification, and structural analysis. The low yields were
      apparently due to low abundance in source tissues, aggravated by enzyme
      instability. Here we describe an immunological method for purification of
      workable quantities from florets of Brassica oleracea ssp. botrytis
      (cauliflower). Florets that had undergone browning due to exposure to sunlight
      contained higher S-GT activities than are normally found in Brassica tissues. S
      GT was adsorbed from crude tissue extracts onto an agarose-monoclonal antibody
      complex. Elution from the complex required harsh alkaline conditions (pH 11.5),
      giving extremely variable activity recoveries (maximum 20%). The eluate contained
      two proteins that could be separated readily by preparative polyacrylamide gel
      electrophoresis or anion-exchange chromatography. The overall S-GT protein
      recovery was estimated at less than 200 [mu]g/kg of cauliflower tissue. Molecular
      weight determinations with homogeneous cauliflower S-GT gave relative molecular
      weight (Mr) values of 55,500 as estimated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and 57,600 by gel chromatography; isoenzymes
      with isoelectric point values of 4.80 and 4.95 were identified. A polyclonal
      antibody raised against denatured enzyme showed broad cross-reactivity in
      immunoblots with S-GT from a number of Brassica species and other crucifers. The
      monoclonal antibody that was used in the immunopurification was much more
      specific; it exclusively precipitated S-GT isoenzymes that had their genomic
      origin in the primary diploids B. oleracea and Brassica campestris. Thus, all of
      the S-GT was precipitated from the amphidiploid Brassica napus, which is a hybrid
      of B. orleracea and B. campestris. About half of the S-GT was precipitated from
      the amphidiploids Brassica carinata and Brassica juncea, which have B. oleracea
      and B. campestris as one of their parents, respectively. It was shown that the S
      GT isoenzymes of B. juncea with Mr 55,500 and about 57,000 originate from the
      parents B. campestris and B. nigra, respectively.

PMID- 12232213
TI  - Methylammonium as a Transport Analog for Ammonium in Tomato (Lycopersicon
      esculentum L.).
AB  - Methylammonium (CH3NH3+) has been widely used as an analog of ammonium (NH4+) for
      examining transport in bacteria and fungi. We compared the kinetics of root
      CH3NH3+ and NH4+ uptake from solution culture in intact tomato (Lycopersicon
      esculentum cv T5) plants. Efflux of NH4+ and CH3NH3+ was negligible. The apparent
      maximum rate of absorption (apparent Vmax) was similar for NH4+ and CH3NH3+, but
      the apparent affinity (apparent Km) was about 10-fold greater for NH4+ than for
      CH3NH3+. In characterizing the interaction between NH4+ and CH3NH3+ transport, we
      used [15N]NH4+ and [14C]CH3NH3+ as well as improved methods for analysis of
      nonisotopic CH3NH3+ and NH4+. CH3NH3+ acted as an inhibitor of NH4+ influx.
      Relatively low concentrations of NH4+ strongly inhibited CH3NH3+ influx.
      Treatments with 1 mM methionine sulfoximine that blocked NH4+ assimilation had
      little influence on NH4+ inhibition of CH3NH3+ influx. These results suggest that
      the two ions share a common transport system in tomato, but because this
      transport system has a much greater affinity for NH4+, CH3NH3+ may be used as a
      transport analog only when ambient concentrations of NH4+ are very low.

PMID- 12232214
TI  - Gametophytic Self-Incompatibility: A Mechanism for Self/Nonself Discrimination
      during Sexual Reproduction.

PMID- 12232215
TI  - Active Oxygen Species in Plant Defense against Pathogens.

PMID- 12232216
TI  - Plant Expression of a Bacterial Cytochrome P450 That Catalyzes Activation of a
      Sulfonylurea Pro-Herbicide.
AB  - The Streptomyces griseolus gene encoding herbicide-metabolizing cytochrome
      P450SU1 (CYP105A1) was expressed in transgenic tobacco (Nicotiana tabacum).
      Because this P450 can be reduced by plant chloroplast ferredoxin in vitro,
      chloroplast-targeted and nontargeted expression were compared. Whereas P450SU1
      antigen was found in the transgenic plants regardless of the targeting, only
      those with chloroplast-directed enzyme performed P450SU1-mediated N-dealkylation
      of the sulfonylurea 2-methylethyl-2,3-dihydro-N-[(4,6-dimethoxypyrimidin-2
      yl)aminocarbonyl]-1, 2-benzoisothiazole- 7-sulfonamide-1,1-dioxide (R7402).
      Chloroplast targeting appears to be essential for the bacterial P450 to function
      in the plant. Because the R7402 metabolite has greater phytotoxicity than R7402
      itself, plants bearing active P450SU1 are susceptible to injury from R7402
      treatment that is harmless to plants without P450SU1. Thus, P450SU1 expression
      and R7402 treatment can be used as a negative selection system in plants.
      Furthermore, expression of P450SU1 from a tissue-specific promoter can sequester
      production of the phytotoxic R7402 metabolite to a single plant tissue. In
      tobacco expressing P450SU1 from a tapetum-specific promoter, treatment of
      immature flower buds with R7402 caused dramatically lowered pollen viability.
      Such treatment could be the basis for a chemical hybridizing agent.

PMID- 12232217
TI  - Complementation of the Tomato anthocyanin without (aw) Mutant Using the
      Dihydroflavonol 4-Reductase Gene.
AB  - We isolated the dihydroflavonol 4-reductase (DFR) gene from tomato (Lycopersicon
      esculentum) using a previously characterized cDNA as probe. Earlier studies had
      indicated that the DFR gene is present in tomato as a single gene located on
      chromosome 2 near the locus anthocyanin without (aw). Mutant alleles of the aw
      locus result in the complete absence of anthocyanin pigmentation throughout all
      stages of plant development. When the genomic DFR clone was introduced by
      Agrobacterium-mediated transformation into plants bearing the aw mutation,
      primary transgenic seedlings accumulated anthocyanins that could be observed
      while the plants were still in tissue culture and which continued to be observed
      as the plants matured. Progeny of self pollinated and backcrossed transgenic
      plants segregated for anthocyanin pigmentation, and Southern hybridization
      analyses indicated the presence of the DFR transgene exclusively in those plants
      with pigmentation. These data indicate that the aw locus likely corresponds to
      the structural gene for DFR and that DFR can be used as a visual, nondestructive,
      plant-derived marker gene for tomato.

PMID- 12232218
TI  - Regulation of Sterol Content in Membranes by Subcellular Compartmentation of
      Steryl-Esters Accumulating in a Sterol-Overproducing Tobacco Mutant.
AB  - The study of sterol overproduction in tissues of LAB 1-4 mutant tobacco
      (Nicotiana tabacum L. cv Xanthi) (P. Maillot-Vernier, H. Schaller, P. Benveniste,
      G. Belliard [1989] Biochem Biophys Res Commun 165: 125-130) over several
      generations showed that the overproduction phenotype is stable in calli, with a
      10-fold stimulation of sterol content when compared with wild-type calli.
      However, leaves of LAB 1-4 plants obtained after two steps of self-fertilization
      were characterized by a mere 3-fold stimulation, whereas calli obtained from
      these plants retained a typical sterol-overproducing mutant phenotype (i.e. a 10
      fold increase of sterol content). These results suggest that the expression of
      the LAB 1-4 phenotype is dependent on the differentiation state of cells. Most of
      the sterols accumulating in the mutant tissues were present as steryl-esters,
      which were minor species in wild-type tissues. Subcellular fractionation showed
      that in both mutant and wild-type tissues, free sterols were associated mainly
      with microsomal membranes. In contrast, the bulk of steryl-esters present in
      mutant tissues was found in the soluble fraction of cells. Numerous lipid
      droplets were detected in the hyaloplasm of LAB 1-4 cells by cytochemical and
      cytological techniques. After isolation, these lipid granules were shown to
      contain steryl-esters. These results show that the overproduced sterols of mutant
      tissues accumulate as steryl-esters in hyaloplasmic bodies. The esterification
      process thus allows regulation of the amount of free sterols in membranes by
      subcellular compartmentation.

PMID- 12232219
TI  - Photopolarization of the Fucus sp. Zygote by Blue Light Involves a Plasma
      Membrane Redox Chain.
AB  - Zygotes of fucoid algae are photopolarized by unidirectional blue light (BL).
      Polar axes are formed, fixed, and expressed by germination of a rhizoid.
      Hexacyanoferrate(III) ions (HCF) specifically inhibit transduction of the BL
      signal. HCF reduction by Fucus sp. zygotes occurs on the outer surface of the
      plasma membrane at higher rates in BL than in dark. These observations suggest
      that BL signal transduction involves a redox chain in the plasma membrane. Low
      doses of HCF (<50 pmol cell-1) inhibit photopolarization but not germination,
      hence uncoupling both processes. Exposure during the photosensitive period to
      higher doses of HCF together with BL significantly inhibits germination. Further
      results suggest that BL transduction is dependent on photosynthetic products that
      could also interact with redox processes.

PMID- 12232220
TI  - Light-Stimulated Carotenoid Biosynthesis during Transformation of Maize
      Etioplasts Is Regulated by Increased Activity of Isopentenyl Pyrophosphate
      Isomerase.
AB  - Light-stimulated carotenoid biosynthesis associated with the transformation of
      etioplasts to chloroplasts was investigated after dark-grown maize (Zea mays)
      seedlings were transferred into light. These studies focused on the enzymes of
      the pathway to detect those enzyme activities that were stimulated in the light
      and thus that were responsible for increased biosynthesis of carotenoids. In
      preliminary experiments, norflurazon, an inhibitor of phytoene desaturase, was
      used to prevent phytoene being further metabolized to carotenoids. Light
      dependent stimulation of phytoene accumulation indicated that the light-regulated
      steps are located in the pathway leading to phytoene synthesis. The use of the
      14C- labeled precursors mevalonic acid, isopentenyl pyrophosphate, and farnesyl
      pyrophosphate pointed to increased activity of an enzyme involved in the
      biosynthetic steps between isopentenyl pyrophosphate and farnesyl pyrophosphate.
      Determination of the activities of all five enzymes of the pathway involved in
      the sequence from mevalonic acid to phytoene revealed that the only enzyme
      activity stimulated by light was isopentenyl pyrophosphate isomerase. Over a 3-h
      period of illumination, this enzyme activity, like carotenoid biosynthesis, was
      stimulated 2.8-fold.

PMID- 12232221
TI  - Growth at Low Temperature Mimics High-Light Acclimation in Chlorella vulgaris.
AB  - Structural and functional alterations to the photosynthetic apparatus after
      growth at low temperature (5[deg]C) were investigated in the green alga Chlorella
      vulgaris Beijer. Cells grown at 5[deg]C had a 2-fold higher ratio of chlorophyll
      a/b, 5-fold lower chlorophyll content, and an increased xanthophyll content
      compared to cells grown at 27[deg]C even though growth irradiance was kept
      constant at 150 [mu]mol m-2 s-1. Concomitant with the increase in the chlorophyll
      a/b ratio was a lower abundance of light-harvesting polypeptides in 5[deg]C-grown
      cells as observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      and confirmed by western blotting.The differences in pigment composition were
      found to be alleviated within 12 h of transferring 5[deg]C-grown cells to
      27[deg]C. Furthermore, exposure of 5[deg]C-grown cells to a 30-fold lower growth
      irradiance (5 [mu]mol m-2 s-1) resulted in pigment content and composition
      similar to that in cells grown at 27[deg]C and 150 [mu]mol m-2 s-1. Although both
      cell types exhibited similar measuring-temperature effects on CO2-saturated O2
      evolution, 5[deg]C-grown cells exhibited light-saturated rates of O2 evolution
      that were 2.8-and 3.9-fold higher than 27[deg]C-grown cells measured at 27[deg]C
      and 5[deg]C, respectively. Steady-state chlorophyll a fluorescence indicated that
      the yield of photosystem II electron transport of 5[deg]C-grown cells was less
      temperature sensitive than that of 27[deg]C-grown cells. This appears to be due
      to an increased capacity to keep the primary, stable quinone electron acceptor of
      photosystem II (QA) oxidized at low temperature in 5[deg]C- compared with
      27[deg]C-grown cells regardless of irradiance. We conclude that Chlorella
      acclimated to low temperature adjusts its photosynthetic apparatus in response to
      the excitation pressure on photosystem II and not to the absolute external
      irradiance. We suggest that the redox state of QA may act as a signal for this
      photosynthetic acclimation to low temperature in Chlorella.

PMID- 12232222
TI  - Cleavage of Chlorophyll-Porphyrin (Requirement for Reduced Ferredoxin and
      Oxygen).
AB  - The chemical structures of some colorless catabolites that accumulate in
      senescent leaves have been established recently (B. Krautler, B. Jaun, W. Amrein,
      K. Bortlik, M. Schellenberg, P. Matile [1992] Plant Physiol Biochem 30: 333-346;
      W. Muhlecker, B. Krautler, S. Ginsburg, P. Matile [1993] Helv Chim Acta 76: 2976
      2980). Such studies suggest that oxygenolytic cleavage of chlorophyll-porphyrin
      may occur by the action of a dioxygenase. We have attempted to demonstrate such
      an enzyme activity and to explore the requirements of the cleavage reaction in a
      reconstituted system of chloroplast (Chlpl) components prepared from senescent
      rape (Brassica napus L.) cotyledons. Intact senescent Chpls (also referred to as
      gerontoplasts) contain small amounts of two fluorescent chlorophyll catabolites,
      Bn-FCC-1 and Bn-FCC-2, probably representing primary cleavage products. Upon the
      incubation of Gpls in the presence of glucose-6-phosphate (Glc6P) or ATP, these
      catabolites (predominantly FCC-1) were produced in organello. In a reconstituted
      system of thylakoids and stroma fraction the FCCs (predominantly FCC-2) were
      produced in the presence of ferredoxin (Fd) and cofactors (NADPH, Glc6P) helping
      to keep Fd in the reduced state. Reduced Fd could not be replaced by other
      electron donors, suggesting that the putative dioxygenase requires Fd for the
      operation of its redox cycle. Production of FCC-2 did not occur in the absence of
      oxygen and it was inhibited by chelators of Fe2+. The contributions to the
      production of FCCs from both parts of the reconstituted system, thylakoids and
      stroma, are heat labile. The enzymic process in the thylakoids yields
      pheophorbide a, the presumptive precursor of FCCs. However, native senescent
      thylakoids could not be replaced as a "substrate" by free pheophorbide a. The
      stromal enzyme appears to have an affinity for senescent thylakoids; thus,
      "loaded" thylakoids capable of FCC production in the presence of Fd and cofactors
      were obtained upon homogenization of senescent cotyledons in a medium containing
      sorbitol and ascorbate. Such thylakoids were inactive if prepared from mature
      green cotyledons. As senescence was induced, the capacity to generate FCCs
      appeared and peaked when about half of the chlorophyll had disappeared from the
      cotyledons. The effectiveness of a relevant inhibitor showed that cytoplasmic
      protein synthesis was required for inducing the catabolic machinery in the loaded
      thylakoids. Thylakoids from mature Chlpls were ineffective as substrate of the
      stromal enzyme prepared from Gpls. However, senescent thylakoids yielded FCCs if
      challenged with stroma from either Chlpls or Gpls. Therefore, the stromal part of
      the system is likely to be a constitutive enzyme, and the pace-setting step of
      the pathway of chlorophyll breakdown seems to be located in the thylakoids.

PMID- 12232223
TI  - Acetylene Reduction by Symbiosomes and Free Bacteroids from Broad Bean (Vicia
      faba L.) Nodules (Role of Oxalate).
AB  - We report the presence of oxalate in the organic acid fraction of broad bean
      (Vicia faba L.) nodule cytosol. Using both high-performance liquid chromatography
      and enzymic assays, high levels of oxalate were detected (70.4 [plus or minus]
      2.4 mM). To study the potential role of oxalate as an energy-yielding substrate
      for nitrogenase activity, free bacteroids were isolated from nodules and found to
      oxidize oxalate in support of C2H2 reduction under O2 tensions that were lower
      than those required to oxidize succinate, another dicarboxylate commonly detected
      in legume nodules. Symbiosomes of broad bean, isolated for the first time from
      amide-producing nodules, were provided with [14C]oxalate and found to have uptake
      kinetics with a lower affinity [Km(oxalate) = 330 [mu]M] than that for free
      bacteroids [Km(oxalate) = 130 [mu]M]. In anaerobic preparations of symbiosomes
      supplied with purified oxyleghemoglobin, O2 consumption was stimulated by oxalate
      from 20.2 [plus or minus] 0.8 nmol O2 min-1mg-1 protein to 24.5 [plus or minus]
      1.1 nmol O2 min-1 mg-1 protein but always remained lower than the rate of O2
      consumption in free bacteroids (32.2 [plus or minus] 1.4 nmol O2 min-1 mg-1
      protein). Under these conditions, C2H2 reduction activity was 9.7 [plus or minus]
      0.8 and 15.1 [plus or minus] 0.9 nmol C2H4 min-1 mg-1 protein for symbiosomes and
      bacteroids, respectively. These data support the suggestion that oxalate may play
      a role as a carbon substrate in support of N2 fixation in broad bean nodules.

PMID- 12232224
TI  - The rolB Gene of Agrobacterium rhizogenes Does Not Increase the Auxin Sensitivity
      of Tobacco Protoplasts by Modifying the Intracellular Auxin Concentration.
AB  - Phenotypical alterations observed in rolB-transformed plants have been proposed
      to result from a rise in intracellular free auxin due to a RolB-catalyzed
      hydrolysis of auxin conjugates(J.J. Estruch, J. Schell, A. Spena [1991] EMBO J
      10: 3125-3128).We have investigated this hypothesis in detail using tobacco
      (Nicotiana tabacum) mesophyll protoplasts isolated from plants transformed with
      the rolB gene under the control of its own promoter (BBGUS 6 clone) or the
      cauliflower mosaic virus 35S promoter (CaMVBT 3 clone). Protoplasts expressing
      rolB showed an increased sensitivity to the auxin-induced hyperpolarization of
      the plasma membrane when triggered with exogenous auxin. Because this
      phenotypical trait was homogeneously displayed over the entire population,
      protoplasts were judged to be a more reliable test system than the tissue
      fragments used in previous studies to monitor rolB gene effects on cellular auxin
      levels. Accumulation of free 1-[3H]-naphthaleneacetic acid (NAA) was equivalent
      in CaMVBT 3, BBGUS 6, and wild-type protoplasts, Naphthyl-[beta]-glucose ester,
      the major NAA metabolite in protoplasts, reached similar levels in CaMVBT 3
      protoplasts, reached similar levels in CaMVBT 3 and normal protoplasts and was
      hydrolyzed at the same rate in BBGUS 6 and normal protoplasts. Furthermore, NAA
      accumulation and metabolism in BBGUS 6 protoplasts were independent of the rolB
      gene expression level. Essentially similar results were obtained with
      indoleacetic acid. Thus, it was concluded that the rolB-dependent behavior of
      transgenic tobacco protoplasts is not a consequence of modifying the
      intracellular auxin concentration but likely results from changes in the auxin
      perception pathway.

PMID- 12232225
TI  - Wound-Associated Competency Factors Are Required for the Proximal Cell Responses
      of Soybean to the Phytophthora sojae Wall Glucan Elicitor.
AB  - Intact soybean (Glycine max L. [Merr.]) tissues show distinct proximal and distal
      cell responses to the Phytophthora sojae (Kauf. and Gerde.) wall glucan elicitor.
      Proximal cells respond with accumulations of glyceollin and phenolic polymers,
      whereas distal cells respond with an increase of isoflavone conjugates.
      Comparison of the activities of the P. sojae glucan in the classical cut
      cotyledon and a cotyledon infiltration assay suggests that the proximal, but not
      the distal, responses to elicitor require tissue wounding. Washing the surface of
      cut cotyledons prior to elicitor treatment also greatly diminishes the proximal
      responses, which can be restored in a dose-dependent manner by prior treatment of
      the washed cells with wound exudate from cut "donor" cotyledons. Thus, discrete
      wound-associated factors, which we term elicitation competency factors, are
      required for the proximal cell response to the glucan elicitor. The wound factors
      induce a competent state that is transient in nature. Maximal elicitor response
      is seen 2 to 3 h after wounding, and cells become elicitor nonresponsive after 4
      h. Competency is markedly affected by the age of tissues; cotyledons become more
      inherently competent as they approach senescence. The time course of attainment
      of the competent state and its duration are strongly affected by light and
      temperature. Since the wound-associated competency factors can also be obtained
      from washings of hypersensitive lesions, we hypothesize that similar competency
      factors may be released from hypersensitively dying cells in incompatible
      infections. This event may program the immediately surrounding cells to make them
      competent for the proximal defense responses.

PMID- 12232226
TI  - Purification and Characterization of Chloroplastic NADP-Isocitrate Dehydrogenase
      from Mixotrophic Tobacco Cells (Comparison with the Cytosolic Isoenzyme).
AB  - Green, mixotrophic tobacco (Nicotiana tabacum) cell cultures in the exponential
      growth phase were found to have two clearly distinguishable NADP-isocitrate
      dehydrogenase (ICDH; EC 1.1.1.42) isoenzymes. Their elution behavior during anion
      exchange column chromatography was similar to that described previously for the
      cytosolic (ICDH1) and chloroplastic (ICDH2) enzymes from pea (Pisum sativum)
      leaves. ICDH2 was absent in etiolated tobacco cell suspensions and appeared
      during the greening process. Both isoforms were purified to apparent
      electrophoretic homogeneity by ammonium sulfate fractionation and anion-exchange
      and affinity chromatography. The isoenzymes were separated on a DEAE-Sephacel
      column, but the most effective step was a Matrex Red-A column, which enabled an
      overall purification of 833- and 1328-fold for ICDH1 and ICDH2, respectively.
      Polyclonal antibodies were raised against each isoform. The ICDH2-specific
      antibody was used to localize tobacco leaf ICDH2 in situ by an immunogold
      labeling technique. The enzyme was found largely, if not exclusively, in the
      chloroplasts of green leaves. ICDH1 and ICDH2 were shown to have apparent native
      molecular weights of 117,000 and 136,000, respectively, and to consist of
      identical, 48.5-kD subunits. Similar apparent Km values for NADP, D(+)isocitrate,
      and Mg2+ were found for the two enzymes when assayed with Mg2+ as the metal
      cofactor.

PMID- 12232227
TI  - Genetic Enhancement of Cold Tolerance by Expression of a Gene for Chloroplast
      [omega]-3 Fatty Acid Desaturase in Transgenic Tobacco.
AB  - The increased production of trienoic fatty acids, hexadecatrienoic (16:3) and
      linolenic (18:3) acids, is a response connected with cold acclimation of higher
      plants and is thought to protect plant cells against cold damage. Transgenic
      tobacco (Nicotiana tabacum cv SR1) plants that contain increased levels of 16:3
      and 18:3 fatty acids, and correspondingly decreased levels of their precursors,
      hexadecadienoic and linoleic acids, were engineered by introduction of a
      chloroplast [omega]-3 fatty acid desaturase gene (the fad7 gene) isolated from
      Arabidopsis thaliana. When exposed to 1[deg]C for 7 d and then cultured at
      25[deg]C, the suppression of leaf growth observed in the wild-type plants was
      significantly alleviated in the transgenic plants with the fad7 gene. The low
      temperature- induced chlorosis was also much reduced in the plants transformed
      with the fad7 gene. These results indicate that increased levels of trienoic
      fatty acids in genetically engineered plants enhance cold tolerance.

PMID- 12232228
TI  - Incorporation of Label from 13C-, 2H-, and 15N-Labeled Methionine Molecules
      during the Biosynthesis of 2[prime]-Deoxymugineic Acid in Roots of Wheat.
AB  - The biosynthetic pathway of 2[prime]-deoxymugineic acid, a key phytosiderophore,
      was investigated by feeding 13C-, 2H-, and 15N-labeled methionine, the first
      precursor, to the roots of hydroponically cultured wheat (Triticum aestivum L. cv
      Minori). The incorporation of label from each methionine species was observed
      during their conversion to 2[prime]-deoxymugineic acid, using 2H-, 15N-, and 13C
      nuclear magnetic resonance (NMR). L-[1-13C]Methionine (99% 13C) was efficiently
      incorporated, resulting in 13C enrichment of the three carboxyl groups of
      2[prime]-deoxymugineic acid. Use of D,L-[15N]methionine (95% 15N) resulted in 15N
      enrichment of 2[prime]-deoxymugineic acid at the azetidine ring nitrogen and the
      secondary amino nitrogen. When D,L-[2,3,3,-2H3-S-methyl-2H3]methionine (98.2% 2H)
      was fed to the roots, 2H-NMR results indicated that only six deuterium atoms were
      incorporated, and that the deuterium atom from the C-2 position of each
      methionine was almost completely lost. [2,2,3,3-2H4]1-Aminocyclopropane-1
      carboxylic acid (98% 2H) was not incorporated into 2[prime]-deoxymugineic acid.
      These data and our previous findings demonstrated that only the deuterium atom
      from the C-2 position of L-methionine was lost, and that other atoms were
      completely incorporated when three molecules of methionine were converted to
      2[prime]-deoxymugineic acid. These observations are consistent with the
      conversion of L-methionine to azetidine-2-carboxylic acid, suggesting that L
      methionine is first converted to azetidine-2-carboxylic acid during biosynthesis
      leading to 2[prime]-deoxymugineic acid. Based on these results, a hypothetical
      pathway from L-methionine to 2[prime]-deoxymugineic acid was postulated.

PMID- 12232229
TI  - Acclimation, Hydrogen Peroxide, and Abscisic Acid Protect Mitochondria against
      Irreversible Chilling Injury in Maize Seedlings.
AB  - Our previous results indicated that 3-d-old dark-grown chilling-sensitive maize
      (Zea mays L.) seedlings did not survive 7 d of 4[deg]C chilling stress, but 69%
      of them survived similar stress when the seedlings were either preexposed to
      14[deg]C for 3 d or pretreated with 0.1 mM H2O2 for 4 h at 27[deg]C (T.K. Prasad,
      M.D. Anderson, B.A. Martin, C.R. Stewart [1994] Plant Cell 6: 65-74) or 1 mM
      abscisic acid (ABA) for 24 h at 27[deg]C (M.D. Anderson, T.K. Prasad, B.A.
      Martin, C.R. Stewart [1994] Plant Physiol 105: 331-339). We discovered that
      chilling imposed oxidative stress on the seedlings. Since H2O2 accumulated during
      the periods of both acclimation and nonacclimation, we concluded that H2O2 had
      dual effects at low temperature: (a) During acclimation, its early transient
      accumulation signals the induction of antioxidant enzymes such as catalase 3 and
      peroxidase to scavenge H2O2; and (b) at 4[deg]C in nonacclimated seedlings, it
      accumulates to damaging levels in the tissues because of low levels of these and
      perhaps other antioxidant enzymes. Three-day-old seedlings pretreated with H2O2
      (a mild oxidative stress) or ABA showed induced chilling tolerance. In the
      present study, we investigated whether mitochondria are a target for chilling
      induced oxidative stress and, if so, what differences do acclimation, H2O2, or
      ABA make to protect mitochondria from irreversible chilling injury. The results
      indicated that chilling, in general, impairs respiratory activity, the cytochrome
      pathway of electron transport, and ATPase activity regardless of the treatment.
      In pretreated seedlings, the activities of catalase 3 and peroxidase in the
      mitochondria increased severalfold compared with control and nonacclimated
      seedlings. The increases in these antioxidant enzymes imply that mitochondria are
      under oxidative stress and such increases could initiate a protective mechanism
      in the mitochondria. Mitochondrial respiration is partially cyanide resistant
      during chilling stress and also after the 1st d of recovery. Upon further
      recovery over 3 d, in contrast to nonacclimated seedlings, the mitochondria of
      acclimation-, H2O2-, and ABA-treated seedlings showed the following recovery
      features. (a) The mitochondrial respiration changed from a cyanide-resistant to a
      cyanide-sensitive cytochrome pathway, (b) cytochrome oxidase activity recovered
      to control levels, (c) the ability of mitochondria to generate ATP was regained,
      and (d) the antioxidant enzyme activities remained at or above control levels.
      Based on these results, we conclude that chilling impairs mitochondrial function
      and that chilling-induced oxidative stress seems to be a factor, at least in
      part, for causing possible irreversible damage to the mitochondrial membrance
      components. Acclimation, H2O2, and ABA provide a protective mechanism by inducing
      antioxidant enzymes to protect mitochondria from irreversible oxidative damage
      that is absent in nonacclimated seedlings. Therefore, we conclude that the
      ability of the seedlings to recover from chilling injury is, at least in part,
      due to the ability of the mitochondria to resume normal function.

PMID- 12232230
TI  - Light-Dependent Tyrosine Phosphorylation in the Cyanobacterium Prochlorothrix
      hollandica.
AB  - A light-dependent tyrosine kinase activity is present in soluble extracts from
      the cyanobacterium Prochlorothrix hollandica. The substrate of this tyrosine
      kinase activity is a soluble 88-kD protein that is phosphorylated when cultures
      of P. hollandica are adapted to high-light conditions. This phosphoprotein was
      identified by probing western blots of 32P-labeled soluble proteins from P.
      hollandica with an antibody specific for phosphotyrosine. This specificity was
      confirmed by competition experiments in which the antibody binding was abolished
      completely in the presence of excess phosphotyrosine but not phosphoserine and
      phosphothreonine. The kinetics of phosphorylation in vivo were determined by
      probing western blots with this antibody. Within 1 h following a switch from
      extended darkness to high light (200 [mu]mol photons m-2 s-1), the 88-kD protein
      was detectable upon India ink staining of western blots. After 3 h, the antibody
      recognized the phosphorylated form of this polypeptide. Within 6 h of a downshift
      from high to low light, the 88-kD protein was dephosphorylated. In vitro
      phosphorylation studies also showed that cell extracts can phosphorylate a
      tyrosine-containing artificial substrate; acid hydrolysis of both the artificial
      substrate and the 88-kD protein showed that phosphorylation occurred exclusively
      on tyrosine residues. Finally, experiments with high-light-adapted Synechococcus
      sp. PCC7942 suggest that a similar tyrosine phosphorylation event occurs in a
      phycobilisome-containing cyanobacterium.

PMID- 12232231
TI  - Retention of Photoinduction of Cytosolic Enzymes in aurea Mutant of Tomato
      (Lycopersicon esculentum).
AB  - The tomato (Lycopersicon esculentum Mill.) aurea (au) mutant has been
      characterized as a phytochrome-deficient mutant lacking spectrally detectable
      phytochrome A in etiolated seedlings. Seedlings of au grown under red light (RL)
      lack phytochrome regulation of nuclear genes encoding plastidic proteins, possess
      ill-developed chloroplasts, and are slow to de-etiolate. In the present study,
      the effect of phytochrome deficiency on photoinduction of enzymes in etiolated au
      seedlings was investigated. The photoinduction of the cytosolic enzymes amylase
      and nitrate reductase (NR) and of the plastidic enzyme nitrite reductase (NiR) in
      au was compared with that in the isogenic wild-type (WT) tomato and the high
      pigment (hp) mutant with exaggerated phytochrome response. In WT and hp, both
      brief RL pulses and continuous RL induced amylase, NR, and NiR activities,
      whereas in au no photoinduction of enzymes was observed with brief RL pulses, and
      continuous RL induced only amylase and NR activities. The time courses of
      photoinduction of NR and amylase in au under continuous RL followed patterns
      qualitatively similar to hp and WT. A blue-light pretreatment prior to continuous
      RL exposure was ineffective in inducing NiR activity in au. Only continuous white
      light could elicit a photoinduction of NiR in au seedlings. The norflurazon
      triggered loss of photoinduction of NiR in WT and hp indicated that NiR
      photoinduction depended on chloroplast biogenesis. The results indicate that
      observed photoinduction of NR and amylase in au may be mediated by a residual
      phytochrome pool.

PMID- 12232232
TI  - Improved Cytoplasmic pH Regulation, Increased Lactate Efflux, and Reduced
      Cytoplasmic Lactate Levels Are Biochemical Traits Expressed in Root Tips of Whole
      Maize Seedlings Acclimated to a Low-Oxygen Environment.
AB  - We tested the hypothesis (J.-H. Xia and P.H. Saglio [1992] Plant Physiol 100: 40
      46) that the enhanced ability of maize (Zea mays) root tips to survive anoxia,
      elicited by a 4-h exposure to 3% O2 ("acclimation"), is due to less cytoplasmic
      acidosis early in anoxia. Cytoplasmic pH and fermentation reactions were
      monitored in excised and intact (attached) maize root tips by simultaneous in
      vivo 13C- and 31P-NMR spectroscopy. We demonstrate that both excised and intact
      acclimated root tips have significantly higher cytoplasmic pH values under
      anoxia. This reduction in cytoplasmic acidosis is greater in intact root tips.
      Remarkably, cytoplasmic pH does not change when root tips are transferred from 3%
      O2 to anoxia. The earlier observation of considerable lactate efflux and lowered
      intracellular lactate in excised, acclimated root tips (ibid.) was extended to
      intact seedlings. The predominant fermentation end product retained in the cells
      of acclimated root tips is alanine. We discuss the relationship between
      cytoplasmic pH and levels of intracellular lactate and alanine in sugar-replete
      roots, and the role of cytoplasmic pH in determining survival under anoxia.

PMID- 12232233
TI  - Uridine Diphosphate Glucose Metabolism and Callose Synthesis in Cultured Pollen
      Tubes of Nicotiana alata Link et Otto.
AB  - Membrane preparations from cultured pollen tubes of Nicotiana alata Link et Otto
      contain a Ca2+ -independent (1-3)-[beta]-D-glucan (callose) synthase activity
      that has a low affinity for UDP-glucose, even when activated by treatment with
      trypsin (H. Schlupmann, A. Basic, S.M. Read [1993] Planta 191: 470-481).
      Therefore, we investigated whether UDP-glucose was a likely substrate for callose
      synthesis in actively growing pollen tubes. Deposition of (1-3)-[beta]-glucan
      occurred at a constant rate, 1.4 to 1.7 nmol glucose min-1, in tubes from 1 mg of
      pollen from 3 h after germination; however, the rate of incorporation of
      radioactivity from exogenous [14C]-sucrose into wall polymers was not constant,
      but increased until at least 8 h after germination, probably due to decreasing
      use of internal reserves. UDP-glucose was a prominent ultraviolet-absorbing
      metabolite in pollen-tube extracts, with 1.6 nmol present in tubes from 1 mg of
      pollen, giving a calculated cytoplasmic concentration of approximately 3.5 mM.
      Radioactivity from [14C]-sucrose was rapidly incorporated into sugar
      monophosphates and UDP-glucose by the growing tubes, consistent with a turnover
      time for UDP-glucose of less than 1 min; the specific radioactivity of extracted
      UDP-[14C]glucose was equal to that calculated from the rate of incorporation of
      [14C]sucrose into wall glucans. Large amounts of less metabolically active
      neutral sugars were also present. The rate of synthesis of (1-3)-[beta]-glucan by
      nontrypsin-treated pollen-tube membrane preparations incubated with 3.5 mM UDP
      glucose and a [beta]-glucoside activator was slightly greater than the rate of
      deposition of (1-3)-[beta]-glucan by intact pollen tubes. These data are used to
      assess the physiological significance of proteolytic activation of pollen-tube
      callose synthase.

PMID- 12232234
TI  - Purification and Characterization of Acetyl-Coenzyme A Carboxylase from Diclofop
      Resistant and -Susceptible Lolium multiflorum.
AB  - Acetyl-coenzyme A carboxylase (ACCase) was purified >100-fold (specific activity
      3.5 units mg-1) from leaf tissue of diclofopresistant and -susceptible biotypes
      of Lolium multiflorum. As determined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, the purified fractions from both biotypes contained a single 206
      kD biotinylated polypeptide. The molecular mass of the native enzyme from both
      biotypes was approximately 520 kD. In some cases the native dimer from both
      biotypes dissociated during gel filtration to form a subunit of approximately 224
      kD. The inclusion of 5% (w/v) polyethylene glycol 3350 (PEG) in the elution
      buffer prevented this dissociation. Steady-state substrate kinetics were analyzed
      in both the presence and absence of 5% PEG. For ACCase from both biotypes,
      addition of PEG increased the velocity 22% and decreased the apparent Km values
      for acetyl-coenzyme A (acetyl-CoA), but increased the Km values for bicarbonate
      and ATP. In the presence of PEG, the Km values for bicarbonate and ATP were
      approximately 35% higher for the enzyme from the susceptible biotype compared
      with the resistant enzyme. In the absence of PEG, no differences in apparent Km
      values were observed for the enzymes from the two biotypes. Inhibition constants
      (Ki app) were determined for CoA, malonyl-CoA, and diclofop. CoA was an S
      hyperbolic (slope replots)-I-hyperbolic (intercept replots) noncompetitive
      inhibitor with respect to acetyl-CoA, with Ki app values of 711 and 795 [mu]M for
      enzymes from the resistant and susceptible biotypes, respectively. Malonyl-CoA
      competitively inhibited both enzymes (versus acetyl-CoA) with Ki app values of
      140 and 104 [mu]M for ACCase from resistant and susceptible biotypes,
      respectively. Diclofop was a linear noncompetitive inhibitor of ACCase from the
      susceptible biotype and a nonlinear, or S-hyperbolic-I-hyperbolic, noncompetitive
      inhibitor of ACCase from the resistant biotype. For ACCase from the susceptible
      biotype the slope (Kis) and intercept (Kii) inhibition constants for diclofop
      versus acetyl-CoA were 0.08 and 0.44 [mu]M, respectively. ACCase from the
      resistant biotype had a Ki app value of 6.5 [mu]M. At a subsaturating acetyl-CoA
      concentration of 50 [mu]M, the Hill coefficients for diclofop binding were 0.61
      and 1.2 for ACCase from the resistant and susceptible biotypes, respectively. The
      Hill coefficients for diclofop binding and the inhibitor replots suggest that the
      resistant form of ACCase exhibits negative cooperativity in binding diclofop.
      However, the possibility that the nonlinear inhibition of ACCase activity by
      diclofop in the enzyme fraction isolated from the resistant biotype is due to the
      presence of both resistant and susceptible forms of ACCase cannot be excluded.

PMID- 12232235
TI  - Localization of Boron in Cell Walls of Squash and Tobacco and Its Association
      with Pectin (Evidence for a Structural Role of Boron in the Cell Wall).
AB  - B deficiency results in a rapid inhibition of plant growth, and yet the form and
      function of B in plants remains unclear. In this paper we provide evidence that B
      is chemically localized and structurally important in the cell wall of plants.
      The localization and chemical fractionation of B was followed in squash plants
      (Curcurbita pepo L.) and cultured tobacco cells (Nicotiana tabacum) grown in B
      replete or B-deficient medium. As squash plants and cultured tobacco cells became
      deficient, an increasingly large proportion of cellular B was found to be
      localized in the cell wall. Cytoplasmic B concentrations were reduced to
      essentially zero as plants became deficient, whereas cell wall B concentration
      remained at or above 10 [mu]g B/g cell wall dry weight in all experiments.
      Chemical and enzymic fractionation studies suggest that the majority of cell B is
      associated with pectins within the cell wall. Physical analysis of B-deficient
      tissue indicates that cell wall plastic extensibility is greatly reduced under B
      deficiency, and anatomical observations indicate that B deficiency impairs normal
      cell elongation in growing plant tissue. In plants in which B deficiency had
      inhibited all plant growth, tissues remained green and did not show any
      additional visible symptoms for at least 1 week with no additional B. This
      occurred even though cytoplasmic B had been reduced to extremely low levels (<0.2
      [mu]g/g). This suggests that B in these species is largely associated with the
      cell wall and that any cytoplasmic role for B is satisfied by very low
      concentrations of B. The localization of B in the cell wall, its association with
      cell wall pectins, and the contingent effects of B on cell wall extensibility
      suggest that B plays a critical, although poorly defined, role in the cell wall
      structure of higher plants.

PMID- 12232236
TI  - Immunolocalization of the Plasma Membrane H+ -ATPase in Minor Veins of Vicia faba
      in Relation to Phloem Loading.
AB  - The immunolocalization of the plasma membrane H+ -ATPase, which generates a
      proton motive force energizing the uptake of inorganic and organic solutes, was
      studied by electron microscopy. The cells studied were in minor veins of Vicia
      faba L. exporting leaves, where photosynthates are supposed to be absorbed from
      the apoplast by phloem transfer cells. Immunologically detectable H+ -ATPase
      varied among the different cell types and was considerably denser in the transfer
      cells than in the other cell types, particularly in the sieve tube. Moreover, the
      distribution of the H+ -ATPase was not homogeneous in transfer cells, that pump
      being more concentrated in the region adjacent to the bundle sheath, phloem
      parenchyma, and xylem vessels than along the smooth part of the wall bordering
      the sieve tube. These results show that the plasma membrane infoldings of
      transfer cells possess the proton-pumping machinery required to energize an
      efficient uptake of photosynthates from the phloem apoplast and an efficient
      retrieval of nitrogenous compounds from the vascular sap.

PMID- 12232237
TI  - Cell Expansion and Tracheary Element Differentiation Are Regulated by
      Extracellular pH in Mesophyll Cultures of Zinnia elegans L.
AB  - The effects of medium pH on cell expansion and tracheary element (TE)
      differentiation were investigated in differentiating mesophyll suspension
      cultures of Zinnia elegans L. In unbuffered cultures initially adjusted to pH
      5.5, the medium pH fluctuated reproducibly, decreasing about 1 unit prior to the
      onset of TE differentiation and then increasing when the initiation of new Tes
      was complete. Elimination of large pH fluctuations by buffering the culture
      medium with 20 mM 2-(N-morpholino)ethanesulfonic acid altered both cell expansion
      and TE differentiation, whereas altering the starting pH of unbuffered culture
      medium had no effect on either process. Cell expansion in buffered cultures was
      pH dependent with an optimum of 5.5 to 6.0. The direction of cell expansion was
      also pH dependent in buffered cultures. Cells elongated at pH 5.5 to 6.0, whereas
      isodiametric cell expansion was predominant at pH 6.5 to 7.0. The onset of TE
      differentiation was delayed when the pH was buffered higher or lower than 5.0.
      However, TEs eventually appeared in cultures buffered at pH 6.5 to 7.0,
      indicating that a decrease in pH to 5.0 is not necessary for differentiation.
      Very large TEs with secondary cell wall thickenings resembling metaxylem
      differentiated in cultures buffered at pH 5.5 to 6.0, which also showed the
      greatest cell expansion. The correlation between cell expansion and delayed
      differentiation of large, metaxylem-like TEs may indicate a link between the
      regulatory mechanisms controlling cell expansion and TE differentiation.

PMID- 12232238
TI  - Multiple Forms of Phospholipase D following Germination and during Leaf
      Development of Castor Bean.
AB  - Multiple molecular forms of phospholipase D (PLD; EC 3.1.4.4) were identified and
      partially characterized in endosperm of germinated seeds and leaves of castor
      bean (Ricinus communis L. var Hale). The different PLD forms were resolved by
      nondenaturing polyacrylamide gel electrophoresis, isoelectric focusing, and size
      exclusion chromatography. PLD was detected with both a PLD activity assay and
      immunoblots with PLD-specific antibodies. There were three major forms of PLD,
      designated types 1, 2, and 3, based on their mobility during nondenaturing
      polyacrylamide gel electrophoresis. Molecular masses of the PLD variants were
      estimated at 330, 230, and 270 kD for the types 1, 2, and 3, respectively.
      Isoelectric points of the native type 1, 2, and 3 PLDs were approximately 6.2,
      4.9, and 4.8. Under the in vitro assay conditions used, the three forms of PLD
      exhibited the same substrate specificity, hydrolyzing phosphatidylcholine (PC),
      phosphatidylethanolamine (PE), and phosphatidylglycerol (PG) but not
      phosphatidylserine (PS) and phosphatidylinositol (PI). The three forms of PLD
      differed in their substrate preferences, and the order of activities was: PLD 1,
      PE > PG = PC; PLD 2, PE > PG > PC; PLD 3, PE = PG = PC. The Km values of PLDs 1,
      2, and 3 for PC were 1.92, 2.62, and 5.18 mM, respectively. These PLDs were
      expressed differentially following seed germination and during leaf development.
      Type 1 was found in the early stages of seedling growth and in young leaves, type
      2 was present in all the tissues and growth stages examined, and type 3 was
      expressed in senescent tissues. The PLDs shifted from largely cytosolic to
      predominantly membrane-associated forms during leaf development. The present
      studies demonstrate the structural heterogeneity of plant PLD and growth stage
      specific expression of different molecular forms. The possible role for the
      occurrence of multiple molecular forms of PLD in cellular metabolism is
      discussed.

PMID- 12232239
TI  - A Sulfhydryl Reagent Modulates Systemic Signaling for Wound-Induced and Systemin
      Induced Proteinase Inhibitor Synthesis.
AB  - The sulfhydryl group reagent p-chloromecuribenzene sulfonic acid (PCMBS), an
      established inhibitor of active apoplastic phloem loading of sucrose in several
      plant species, is shown to be a powerful inhibitor of wound-induced and systemin
      induced activation of proteinase inhibitor synthesis and accumulation in leaves
      of tomato plants (Lycopersicon esculentum cv Castlemart). PCMBS, supplied to
      young tomato plants through their cut stems, blocks accumulation of proteinase
      inhibitors in leaves in response to wounding. The application of systemin
      directly to fresh wounds enhances systemic accumulation of proteinase inhibitors
      to levels higher than wounding alone. Placed on fresh wounds, PCMBS severely
      inhibits systemic induction of proteinase inhibitors, in both the presence and
      absence of exogenous systemin. PCMBS inhibition can be reversed by cysteine,
      dithiothreitol, and glutathione. Radiolabeled systemin placed on fresh wounds is
      readily transported from the wounded leaves to upper leaves. However, in the
      presence of PCMBS, radiolabeled systemin is not transported away from wound
      sites. Induction of proteinase inhibitor I synthesis by oligouronides (degree of
      polymerization [almost equal to] 20), linolenic acid, or methyl jasmonate was not
      inhibited by PCMBS. The cumulative data support a possible role for sulfhydryl
      groups in mediating the translocation of systemin from wound sites to distal
      receptor sites in tomato plants and further support a role for systemin as a
      systemic wound signal.

PMID- 12232240
TI  - Evidence That 2-Carboxyarabinitol 1-Phosphate Binds to Ribulose-1,5-Bisphosphate
      Carboxylase in Vivo.
AB  - An important question concerning the role of carboxyarabinitol 1-phosphate (CA1P)
      metabolism in the light-dependent regulation of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco) activity is the extent to which CA1P is bound to
      Rubisco in vivo. We report here the development of an extraction procedure using
      ammonium sulfate that stabilizes CA1P bound to Rubisco. This procedure exploits
      the ability of sulfate to bind at the catalytic site of Rubisco and to
      competitively balance the binding and release of CA1P from Rubisco. In darkened
      bean leaves about 75% of the Rubisco catalytic sites were found to be bound with
      CA1P. This confirms previous indirect estimates from gas exchange measurements.
      We have used this extraction procedure to examine CA1P-Rubisco interactions in
      bean during a natural transition from darkness to light. With increasing light
      intensity following sunrise, CA1P degradation proceeded in two distinct phases:
      first, a majority of the unbound CA1P pool was degraded at very low light levels
      ([less than or equal to]30 [mu]mol quanta m-2 s-1); second, CA1P initially bound
      to Rubisco was then degraded at increasing light levels (>30 [mu]mol quanta m-2 s
      1). These results indicate that there is a low-fluence activation of CA1P
      phosphatase that can occur prior to CA1P release by Rubisco activase. This
      activation may be mediated by NADPH. During sunrise in bean, the level of the
      catalytically competent form of Rubisco was regulated by CA1P metabolism.

PMID- 12232241
TI  - The Elusive Plant Mitochondrion as a Genetic System.

PMID- 12232242
TI  - Root Hair Deformation Activity of Nodulation Factors and Their Fate on Vicia
      sativa.
AB  - We used a semiquantitative root hair deformation assay for Vicia sativa (vetch)
      to study the activity of Rhizobium leguminosarum bv viciae nodulation (Nod)
      factors. Five to 10 min of Nod factor-root interaction appears to be sufficient
      to induce root hair deformation. The first deformation is visible within 1 h, and
      after 3 h about 80% of the root hairs in a small susceptible zone of the root are
      deformed. This zone encompasses root hairs that have almost reached their maximal
      size. The Nod factor accumulates preferentially to epidermal cells of the young
      part of the root, but is not restricted to the susceptible zone. In the
      interaction with roots, the glucosamine backbone of Nod factors is shortened,
      presumably by chitinases. NodRlv-IV(C18:4,Ac) is more stable than NodRlv
      V(C18:4,Ac). No correlation was found between Nod factor degradation and
      susceptibility. Degradation occurs both in the susceptible zone and in the mature
      zone. Moreover, degradation is not affected by NH4NO3 and is similar in vetch and
      in the nonhost alfalfa (Medicago sativa).

PMID- 12232243
TI  - Ion Channels in the Xylem Parenchyma of Barley Roots (A Procedure to Isolate
      Protoplasts from This Tissue and a Patch-Clamp Exploration of Salt Passageways
      into Xylem Vessels.
AB  - To identify mechanisms for the simultaneous release of anions and cations into
      the xylem sap in roots, we investigated voltage-dependent ion conductances in the
      plasmalemma of xylem parenchyma cells. We applied the patch-clamp technique to
      protoplasts isolated from the xylem parenchyma by differential enzymic digestion
      of steles of barley roots (Hordeum vulgare L. cv Apex). In the whole-cell
      configuration, three types of cation-selective rectifiers could be identified:
      (a) one activated at membrane potentials above about -50 mV; (b) a second type of
      outward current appeared at membrane potentials above +20 to +40 mV; (c) below a
      membrane potential of approximately -110 mV, an inward rectifier could be
      distinguished. In addition, an anion-specific conductance manifested itself in
      single-channel activity in a voltage range extending from about -100 to +30 mV,
      with remarkably slow gating. In excised patches, K+ channels activated at
      hyperpolarization as well as at depolarization. We suggest that salt is released
      from the xylem parenchyma into the xylem apoplast by simultaneous flow of cations
      and anions through channels, following electrochemical gradients set up by the
      ion uptake processes in the cortex and, possibly, the release and reabsorption of
      ions on their way to the xylem.

PMID- 12232244
TI  - Isolation of Temperature-Sensitive Mutants of Arabidopsis thaliana That Are
      Defective in the Redifferentiation of Shoots.
AB  - Three temperature-sensitive mutants of Arabidopsis thaliana that were defective
      in the redifferentiation of shoots were isolated as tools for the study of
      organogenesis. M3 lines were constructed by harvesting M3 seeds separately from
      each M2 plant. Comparative examination of shoot redifferentiation in root
      explants of 2700 M3 lines at 22[deg]C (permissive temperature) and at 27[deg]C
      (restrictive temperature) led to the identification of seven temperature
      sensitive mutant lines. Genetic tests of three of the seven mutant lines
      indicated that temperature-sensitive redifferentiation of shoots in these three
      lines resulted from single, nuclear, recessive mutations in three different
      genes, designated SRD1, SRD2, and SRD3. The morphology of root explants of srd
      mutants cultured at the restrictive temperature suggests that the products of
      these SRD genes function at different stages of the redifferentiation of shoots.

PMID- 12232245
TI  - Effects of Abscisic Acid Metabolites and Analogs on Freezing Tolerance and Gene
      Expression in Bromegrass (Bromus inermis Leyss) Cell Cultures.
AB  - Optical isomers and racemic mixtures of abscisic acid (ABA) and the ABA
      metabolites abscisyl alcohol (ABA alc), abscisyl aldehyde (ABA ald), phaseic acid
      (PA), and 7[prime]hydroxyABA (7[prime]OHABA) were studied to determine their
      effects on freezing tolerance and gene expression in bromegrass (Bromus inermis
      Leyss) cell-suspension cultures. A dihydroABA analog (DHABA) series that cannot
      be converted to PA was also investigated. Racemic ABA, (+)-ABA, ([plus or minus])
      DHABA, and (+)-DHABA were the most active in inducing freezing tolerance, (-)
      ABA, ([plus or minus])-7[prime]OHBA, (-)-DHABA, ([plus or minus])-ABA ald, and
      ([plus or minus])-ABA alc had a moderate effect, and PA was inactive. If the
      relative cellular water content decreased below 82%, dehydrin gene expression
      increased. Except for (-)-ABA, increased expression of dehydrin genes and
      increased accumulation of responsive to ABA (RAB) proteins were linked to
      increased levels of frost tolerance. PA had no effect on the induction of RAB
      proteins; however, ([plus or minus])- and (+)-DHABA were both active, which
      suggests that PA is not involved in freezing tolerance. Both (+)-ABA and (-)-ABA
      induced dehydrin genes and the accumulation of RAB proteins to similar levels,
      but (-)-ABA was less effective than (+)-ABA at increasing freezing tolerance. The
      (-)-DHABA analog was inactive, implying that the ring double bond is necessary in
      the (-) isomers for activating an ABA response.

PMID- 12232246
TI  - Nitrogen Reserve Mobilization during Regrowth of Medicago sativa L.
      (Relationships between Availability and Regrowth Yield).
AB  - An experiment was designed to study the role of N and C reserves on regrowth of
      the shoots following defoliation of forage species. Starch and N accumulation in
      root and crown tissue of nonnodulated Medicago sativa L. were modified during
      regrowth by applying different levels of N and different cutting heights. Plants
      were obtained with similar crown and root dry weights, but having either low
      starch and high tissue N or high starch and low tissue N. The plants were then
      submitted to a second defoliation and supplied with optimal N nutrition, and N
      flow from reserve was quantified using pulse-chase 15N labeling. Maximum yields
      following the second regrowth were obtained from those plants having a high
      tissue N, despite their low level of nonstructural carbohydrate. When N in the
      roots and crown exceeded 5 mg N plant-1 at the beginning of regrowth, about 68%
      was translocated to regrowing shoots. Highly significant correlations were also
      found between the amounts of N available in roots and crown at the beginning of
      regrowth and (a) the amount of N that was mobilized to new tissues, (b) the
      amount of N taken up during the regrowth period, and (c) the final shoot yield
      after 24 d of regrowth. No similar correlations were found for plants that varied
      in their initial starch content of roots and crown. It is suggested that N
      reserves were used mainly during the first 10 d after defoliation, and that the
      resulting aerial growth during this period should be sufficient to restore N2
      fixation and/or N uptake to levels equal to those prior to defoliation. These
      data emphasize (a) the importance of root N reserves in initiating and sustaining
      new shoot growth, and (b) the need for a re-evaluation of the contribution of C
      reserves to shoot regrowth.

PMID- 12232247
TI  - Microsensor Analysis of Oxygen in the Rhizosphere of the Aquatic Macrophyte
      Littorella uniflora (L.) Ascherson.
AB  - Oxygen released by the roots of submerged plants may oxidize organic compounds
      from the roots and reduced substances continuously supplied by diffusion from the
      surrounding anoxic hydrosoil. We provide here the first visualization of this
      gradient environment obtained by microsensor analysis of oxygen in the
      rhizosphere of the freshwater plant Littorella uniflora (L.) Ascherson. The
      plants were rooted in an agar medium, in which amorphous FeS provided the main
      oxygen sink. The oxygen concentration at the root surface ranged from 20 to 450
      [mu]M (atmospheric saturation = 280 [mu]M) between darkness and saturating light,
      and the oxic shell surrounding the roots varied from about 0.5 to 5 mm in
      thickness. The oxygen flux from the roots was a saturating function of the
      incident light intensity on the leaves, and the oxygen released was consumed
      mainly at the fluctuating oxic/anoxic interface. The oxic zones around individual
      roots are under dynamic control by light, root morphology, root density, and
      sediment reducing capacity, and, therefore, oxygen concentrations should be
      subject to substantial diurnal fluctuations in dense Littorella populations in
      nutrient-poor sediments.

PMID- 12232248
TI  - The Two Km's for ATP of Corn-Root H+-ATPase and the Use of Glucose-6-Phosphate
      and Hexokinase as an ATP-Regenerating System.
AB  - Plasma membrane vesicles derived from corn (Zea mays L.) roots retain a membrane
      bound H+-ATPase that is able to form a H+ gradient across the vesicle membranes.
      The activity of this ATPase is enhanced 2- to 3-fold when Triton X-100 or
      lysophosphatidylcholine is added to the medium at a protein:detergent ratio of
      2:1 (w/w). In the absence of detergent, the ATPase exhibits only one Km for ATP
      (0.1-0.2 mM), which is the same as for the pumping of H+. After the addition of
      either Triton X-100 or lysophosphatidylcholine, two Km's for ATP are detected,
      one in the range of 1 to 3 [mu]M and a second in the range of 0.1 to 0.2 mM. The
      Vmax of the second Km for ATP increases as the temperature of the assay medium is
      raised from 15[deg]C to 38[deg]C. The Arrhenius plot reveals a single break at
      30[deg]C, both in the absence and in the presence of detergents. In the presence
      of Triton X-100 the H+-ATPase catalyzes the cleavage of glucose-6-phosphate when
      both hexokinase and ADP are included in the assay medium. There is no measurable
      cleavage when the apparent affinity for ATP of the H+-ATPase is not enhanced by
      Triton X-100 or when 1 mM glucose is included in the assay medium. These data
      indicate that when the high-affinity Km for ATP is unmasked with the use of
      detergent, the ATPase can use glucose-6-phosphate and hexokinase as an ATP
      regenerating system.

PMID- 12232249
TI  - Induction of Enzymes Associated with Lysigenous Aerenchyma Formation in Roots of
      Zea mays during Hypoxia or Nitrogen Starvation.
AB  - Either hypoxia, which stimulates ethylene biosynthesis, or temporary N
      starvation, which depresses ethylene production, leads to formation of aerenchyma
      in maize (Zea mays L.) adventitious roots by extensive lysis of cortical cells.
      We studied the activity of enzymes closely involved in either ethylene formation
      (1-amino-cyclopropane-1-carboxylic acid synthase [ACC synthase]) or cell-wall
      dissolution (cellulase). Activity of ACC synthase was stimulated in the apical
      zone of intact roots by hypoxia, but not by anoxia or N starvation. However, N
      starvation, as well as hypoxia, did enhance cellulase activity in the apical
      zone, but not in the older zones of the same roots. Cellulase activity did not
      increase during hypoxia or N starvation in the presence of
      aminoethoxyvinylglycine, an inhibitor of ACC synthase, but this inhibition of
      cellulase induction was reversed during simultaneous exposure to exogenous
      ethylene. Together these results indicate both the role of ethylene in signaling
      cell lysis in response to two distinct environmental factors and the significance
      of hypoxia rather than anoxia in stimulation of ethylene biosynthesis in maize
      roots.

PMID- 12232250
TI  - Early Gravi-Electrical Responses in Bean Epicotyls.
AB  - The relationship between gravitropism and surface electrical potentials was
      studied using etiolated epicotyls of adzuki bean (Phaseolus angularis). Early
      downward curvature (or transient positive gravitropic response) was observed
      about 1 min after gravistimulation. The downward curvature was closely related to
      the speed of the subsequent upward curvature. Surface electrical potentials
      decreased cooperatively in a limited region on the upper side within only 0.5 to
      2 min. This is the earliest event found so far to follow gravistimulation of
      intact epicotyls. The rapid change in the potential had a high correlation with
      the early downward curvature and also the subsequent negative gravitropism. It is
      suggested that the rapid potential change plays an important role in gravity
      perception.

PMID- 12232251
TI  - Role of Endogenous Abscisic Acid in Potato Microtuber Dormancy.
AB  - Potato (Solanum tuberosum L. cv Russet Burbank) microtubers generated in vitro
      from single-node explants contained substantial amounts (approximately 250 pmol/g
      fresh weight) of free abscisic acid (ABA) and were completely dormant for a
      minimum of 12 weeks. Microtubers that developed in the presence of 10 [mu]M
      fluridone (FLD) contained considerably reduced amounts (approximately 5-25 pmol/g
      fresh weight) of free ABA and exhibited a precocious loss of dormancy. Inclusion
      of exogenous racemic ABA in the FLD-containing medium suppressed the premature
      sprouting of these microtubers in a dose-dependent manner. At a concentration of
      50 [mu]M, exogenous ABA restored internal ABA levels to control values and
      completely inhibited FLD-induced precocious sprouting. Exogenous jasmonic acid
      was ineffective in suppressing FLD-induced sprouting. Application of FLD to
      preformed, fully dormant microtubers also resulted in a reduction in internal ABA
      content and precocious sprouting. These results indicate that endogenous ABA is
      essential for the induction and maintenance of potato microtuber dormancy.

PMID- 12232252
TI  - Phosphatidate Kinase, A Novel Enzyme in Phospholipid Metabolism (Characterization
      of the Enzyme from Suspension-Cultured Catharanthus roseus Cells).
AB  - Phosphatidate kinase (adenosine 5[prime]-triphosphate:phosphatidic acid
      phosphotransferase), a novel enzyme of phospholipid metabolism, was detected
      recently in the plasma membranes of suspension-cultured Catharanthus roseus cells
      and purified (J.B. Wissing, H. Behrbohm [1993] Plant Physiol 102: 1243-1249). In
      the present work the properties of phosphatidate kinase are described. The enzyme
      showed a pH optimum of 6.1 and an isoelectric point of 4.8, and was rather stable
      in the presence of its substrates. Although the kinase accepted both ATP and GTP,
      with Km values of about 12 and 18 [mu]M, respectively, the only lipid substrate
      was phosphatidic acid; neither lysophosphatidic acid nor any other lipid tested
      was phosphorylated. With 32P- and 14C-labeled diacylglycerol pyrophosphate, the
      product of the enzyme, it was shown that the kinase catalyzes a reversible
      reaction. The activity of the extracted enzyme depended on the presence of
      surfactants such as Triton X-100 or [beta]-octylglucoside, whereas deoxycholate
      was strongly inhibitory. Kinetic analysis with Triton X-100/phosphatidate mixed
      micelles performed according to the "surface dilution" kinetic model showed
      saturation kinetics with respect to both bulk and surface concentration of
      phosphatidate. The interfacial Michaelis constant for phosphatidate was
      determined as 0.6 mol %.

PMID- 12232253
TI  - Microheterogeneous Cytosolic High-Mobility Group Proteins from Broccoli Co-Purify
      with and Are Phosphorylated by Casein Kinase II.
AB  - A group of low molecular weight protein substrates was found to co-purify with
      casein kinase II from broccoli (Brassica oleracea var italica). These substrates
      showed very high affinity toward casein kinase II and were efficiently
      phosphorylated even in the presence of an excess of exogenous substrates. The
      broccoli substrates were purified from cytosolic extracts as a double band of
      related proteins migrating at 18.7 and 20 kD. Further microheterogeneity was
      revealed by anion-exchange high-performance liquid chromatography and mass
      spectroscopy. The actual molecular masses of the three major components
      identified by mass spectroscopy were determined to be 12,691, 13,256, and 14,128
      D. The substrates showed characteristic amino acid composition with a high
      content of polar amino acids, including about 20% each of acidic and basic amino
      acids. They were soluble in 2% trichloroacetic acid. The substrates cross-reacted
      with an antibody against wheat high-mobility group protein d (HMGd) but not HMGa.
      The isolated broccoli HMGs showed general DNA-binding activity without preference
      for AT-rich DNA. The presence of these HMG proteins in the cytosolic fraction is
      similar to the distribution characteristics of the animal HMG-1 subgroup. On the
      basis of amino acid composition and DNA-binding specificity, the isolated
      broccoli HMGs resemble other plant HMGs homologous to the HMG-1 subgroup.

PMID- 12232254
TI  - Putrescine Channels in the Plasma Membrane of Arabidopsis thaliana.
AB  - The patch-clamp technique was used in the whole-cell configuration to study
      plasma membrane channels permeable to the diamine putrescine in protoplasts
      isolated from cultured cells of Arabidopsis thaliana L. Under our experimental
      conditions, no channels selectively mediating putrescine influx were observed.
      Inward K+ channels showed a low permeability to putrescine, the permeability
      ratio of putrescine relative to K+ being around 0.1. Further characterization of
      the previously identified outward channels mediating putrescine efflux (R.
      Colombo, R. Cerana, N. Bagni [1992] Biochem Biophys Res Commun 182: 1187-1192)
      indicated that their activity was regulated by the overall ion concentration of
      the external medium.

PMID- 12232255
TI  - Are Redox Reactions Involved in Regulation of K+ Channels in the Plasma Membrane
      of Limnobium stoloniferum Root Hairs?
AB  - The effects of the impermeant electron acceptor hexacyanoferrate III (HCF III)
      and the potassium channel blocker tetraethylam-monium (TEA) on the current
      voltage relationship and electrical potential across the plasma membrane of
      Limnobium stoloniferum root hairs was investigated using a modified sucrose gap
      technique. One millimolar HCF III immediately and reversibly depolarized the
      membrane by 27 mV, whereas the effect on the trans-membrane current was markedly
      delayed. After 6 min of treatment with this electron acceptor, outwardly
      rectifying current was inhibited by 50%, whereas the inwardly rectifying current
      was activated approximately 3-fold. Ten millimolar TEA blocked both outward (65%)
      and inward (52%) currents. Differential TEA-sensitive current was shown to be
      blocked (55%) by HCF III at -20 mV and was shown to be stimulated (230%) by this
      electron acceptor at -200 mV. The inward current at -200 mV was eliminated in the
      absence of K+ or after addition of 10 mM Cs+ and was not affected by addition of
      either 10mM Na+ or Li+, independent of the presence of HCF III. The addition of
      any alkali cation to the external medium decreased the outward current both in
      the presence and in the absence of HCF III. The membrane depolarization evoked by
      HCF III did not correlate with the corresponding modification of the inward
      current. HCF III is proposed to activate inwardly rectifying potassium channels
      and to inactivate outwardly rectifying potassium channels. It is concluded that
      the plasma membrane depolarization did not result from modulation of the
      potassium channels by HCF III and may originate from trans-plasma membrane
      electron transfer.

PMID- 12232257
TI  - Genetic Regulation of Development in Sorghum bicolor (VIII. Shoot Growth,
      Tillering, Flowering, Gibberellin Biosynthesis, and Phytochrome Levels Are
      Differentially Affected by Dosage of the ma3R Allele.
AB  - Sorghum [Sorghum bicolor (L.) Moench] homozygous for ma3R lacks a type II, light
      stable phytochrome of 123 kD and has a number of phenotypic characteristics
      consistent with the absence of functional phytochrome B. We have used plants
      heterozygous at Ma3 (Ma3/ma3R and ma3/ma3R) to determine the effect of dosage of
      ma3R on plant growth, flowering, gibberellin (GA) levels, and content of the 123
      kD phytochrome. Both Ma3/ma3R and ma3/ma3R produced the same number of tillers
      per plant as their respective homozygous non-ma3R parents. Height of the
      heterozygotes was intermediate between the homozygous parents, although it was
      more similar to the non-ma3R genotypes. In both field and growth-chamber
      environments, the timing of floral initiation and anthesis in the heterozygotes
      also was intermediate, again more similar to non-ma3R plants. In Ma3/ma3R, levels
      of GA53, GA19, GA20, and GA1 were almost exactly intermediate between levels
      detected in Ma3/Ma3 and ma3R/ma3R plants. Immunoblot analysis indicated that
      there was less of the 123-kD phytochrome in Ma3/ma3R than in homozygous Ma3,
      whereas none was detected in ma3R/ma3R. The degree of dominance of Ma3 and ma3
      over ma3R varies with phenotypic trait, indicating that mechanisms of activity of
      the 123-kD phytochrome vary among the biochemical processes involved in each
      phenotypic character. Although the heterozygotes were similar to homozygous Ma3
      and ma3 plants in growth and flowering behavior, Ma3/ma3R contained 50% less of
      the bioactive GA (GA1) than non-ma3R genotypes. Thus, sensitivity to endogenous
      GAs also may be regulated by the 123-kD phytochrome. To fully regulate plant
      growth and development, two copies of Ma3 or ma3 are required to produce
      sufficient quantities of the light-stable, 123-kD phytochrome.

PMID- 12232258
TI  - Endo-1,4-[beta]-Glucanase, Xyloglucanase, and Xyloglucan Endo-Transglycosylase
      Activities Versus Potential Substrates in Ripening Tomatoes.
AB  - In ripening fruits of tomato (Lycopersicon esculentum L. var 83-G-38), the
      amounts of cellulose and xyloglucan (XG) remained constant during tissue
      softening, but the relative molecular weight (Mr) of XG decreased markedly and
      the Mr of cellulose declined slightly. These changes could have been due to
      activities of non-specific endo-1,4-[beta]-glucanases and/or buffer-soluble XG
      endo-transglycosylase, both of which increased when tissue firmness declined most
      rapidly. Tomato extracts also reduced the viscosity of XG solutions, especially
      in the presence of added XG oligosac-charides. This depolymerizing (XGase)
      capacity differed from [beta]-glucanase and XG transglycosylase activity (a) by
      being almost entirely buffer insoluble, and (b) by declining precipitously during
      fruit softening. Although it disappeared from ripe fruit, XGase may have
      functioned in promoting wall loosening at earlier stages of fruit development
      when its activity was highest. By contrast, during aging of fruit in the ripening
      inhibited mutant rin there was no change in Mr of XG or cellulose, and activities
      of [beta]-glucanases and XG transglycosylase were lower than in wild-type tomato.
      Nevertheless, some softening of the fruit did take place over time and XG amounts
      declined, possibly because high XGase activity was maintained in the mutant,
      unlike in wild-type fruit.

PMID- 12232259
TI  - Proline Accumulation in Maize (Zea mays L.) Primary Roots at Low Water Potentials
      (I. Requirement for Increased Levels of Abscisic Acid).
AB  - Previous work showed that the concentration of proline (Pro) increases greatly in
      the primary root tip of maize (Zea mays L.) at low water potentials ([psi]w). It
      was also shown that the maintenance of root elongation at low [psi]w depends on
      increased levels of abscisic acid (ABA). In this study we have assessed whether
      ABA is required for the increase in Pro concentration. Seedlings were grown in
      vermiculite of various [psi]w, and endogenous ABA levels were decreased using
      either fluridone (FLU) or the vp5 mutant to inhibit carotenoid (and ABA)
      synthesis. In both treatments, Pro concentrations at low [psi]w were
      substantially decreased throughout the apical centimeter, which encompassed the
      elongation zone. Pro concentrations in FLU-treated roots were restored by
      addition of 7 [mu]M ABA to the vermiculite, which raised the internal ABA content
      to the level in untreated roots at the same [psi]w. Pro and water content
      profiles were combined with published growth-velocity distributions to calculate
      the distribution of net Pro and water deposition rates using the continuity
      equation. At a [psi]w of -1.6 MPa, the rate of Pro deposition in the root tip was
      decreased by 75% in FLU-treated compared to untreated roots. FLU treatment
      increased root diameter and, therefore, water content per unit length, but water
      deposition rates decreased due to the dominant influence of reduced longitudinal
      expansion. Thus, the decrease in Pro concentration was attributable entirely to
      the decrease in Pro deposition. The results demonstrate that increased ABA is
      required for high rates of Pro deposition and, thereby, high Pro concentrations
      in the growing region of maize primary roots at low [psi]w.

PMID- 12232260
TI  - A Cationic Channel in the Guard Cell Tonoplast of Allium cepa.
AB  - Stomatal movements depend on an osmoregulation process in which swelling or
      shrinking of the guard cells opens or closes the stomatal pore. Ions and water
      fluxes are an essential aspect of guard cell osmoregulation. Thus far, studies of
      these fluxes have focused on the guard cell plasma membrane. Guard cells,
      however, are a multi-compartment system that includes a prominent vacuole, which
      has a primary role in turgor regulation. This study reports on a detailed
      characterization of an ion channel at the guard cell tonoplast of Allium cepa
      (onion). We used patch-clamp methodology with isolated tonoplast patches to study
      conduction and gating at the single channel level. A voltage-dependent outward
      rectifying cationic channel (210 picosiemens) was the dominant conductance. In
      symmetrical solutions the channel displayed an ohmic behavior in its current
      voltage relationship. It also showed a very large rectification in the open
      probability. The channel was predominantly cationic and its sequence of ionic
      selectivity was weak (Na+ > K+ > Rb+ > Cs+). The channel conductance was not
      affected by intravacuolar pH. Analysis of membrane patches with multiple channels
      showed that the probability of a channel to open was independent of the opening
      of the other channels present in the patch and that there was a conservation of
      the open probability for different channels. Ensemble records generated using a
      pulse protocol showed slow activation and deactivation kinetics. A first-latency
      analysis of single-channel records in response to protocols with different
      prepulse duration indicated that this channel has more than one closed state.

PMID- 12232261
TI  - Dependence of the Extent and Direction of Average Stomatal Response in Zea mays
      L. and Phaseolus vulgaris L. on the Frequency of Fluctuations in Environmental
      Stimuli.
AB  - Stomatal responses to fluctuating light and CO2 were investigated in Zea mays and
      Phaseolus vulgaris. Slow-moving stomata can affect carbon gain and water loss by
      plants during light flecks, under dynamic cloud cover, during alternating windy
      and calm air conditions (which influence CO2 concentrations and humidity
      immediately around leaves in plant canopies), at natural CO2 vents, or in growth
      chambers with imperfect CO2 control. It was found that the frequency of constant
      amplitude fluctuations in light and CO2 dramatically affected the time-averaged
      stomatal conductance in both Zea and Phaseolus. During oscillations in light,
      average stomatal conductance was driven either above or below that observed at
      steady state at the average light level, depending on the frequency of the
      oscillations. Under oscillating CO2, the departure of average stomatal
      conductance away from that observed at steady state at the average CO2 level was
      also frequency dependent in both species. Upon cessation of oscillations and
      return of light or CO2 to the stable median level, stomatal conductance also
      returned to a steady state, matching that before oscillations were initiated.
      This work shows that fluctuations in light and CO2, and equally important, their
      frequency, can be critical in determining time-averaged stomatal conductance
      under unstable environmental conditions.

PMID- 12232262
TI  - Sensitivity Thresholds and Variable Time Scales in Plant Hormone Action.

PMID- 12232263
TI  - Coordination of Chloroplastic Metabolism in N-Limited Chlamydomonas reinhardtii
      by Redox Modulation (I. The Activation of Phosphoribulosekinase and Glucose-6
      Phosphate Dehydrogenase Is Relative to the Photosynthetic Supply of Electrons).
AB  - Extraction of Chlamydomonas reinhardtii CW-15 cells by rapid freezing and thawing
      demonstrates that the in vivo activity of the algal glucose-6-phosphate
      dehydrogenase (G6PDH) is inhibited by the presence of light and activated in the
      dark, whereas phosphoribulosekinase (PRK) is light activated and inhibited in the
      dark. The effects of darkening are reversed by incubation with dithiothreitol
      (DTT) and mimicked by chemical oxidants, indicating that, as in higher plants,
      reduction via the ferredoxin-thioredoxin system likely regulates these enzymes.
      The two enzymes varied in their sensitivity to reduction; the inclusion of 0.5 mM
      DTT during extraction inhibited G6PDH, whereas PRK required treatment with 40 mM
      DTT for 1 h to reach maximum activation. The activation change for both enzymes
      was nearly complete within the 1st min after cells were transferred between light
      and dark, but the level of activation was relative to the incident light at low
      intensities; G6PDH activity decreased with increasing light, whereas PRK became
      more active. The reductive inhibition of G6PDH saturated at very low light,
      whereas PRK activation kinetics closely followed the increase in photosynthetic
      oxygen evolution. These results indicate that light-driven redox modulation of
      G6PDH and PRK is more than an on/off switch, but acts to optimize the reduction
      and oxidation of carbon in the chloroplast in accordance with the supply of
      electrons.

PMID- 12232264
TI  - Coordination of Chloroplastic Metabolism in N-Limited Chlamydomonas reinhardtii
      by Redox Modulation (II. Redox Modulation Activates the Oxidative Pentose
      Phosphate Pathway during Photosynthetic Nitrate Assimilation).
AB  - The onset of photosynthetic NO3- assimilation in N-limited Chlamydomonas
      reinhardtii increased the initial extractable activity of the glucose-6-phosphate
      dehydrogenase (G6PDH), the key regulatory step of the oxidative pentose phosphate
      pathway. The total activated enzyme activity did not change upon NO3- resupply.
      The higher activity, therefore, represents activation of existing enzyme. No
      activation occurred during NH4+ assimilation. Incubation of extracts with DTT
      reversed the NO3- stimulation of G6PDH activity, indicating that the activation
      involved redox modulation of G6PDH. Phosphoribulosekinase, an enzyme activated by
      thioredoxin reduction, was inhibited at the onset of NO3- assimilation. A 2-fold
      stimulation of O2 evolution and a 70% decrease in the rate of photosynthetic CO2
      assimilation accompanied the enzyme activity changes. There was an immediate drop
      in the NADPH and an increase in NADP upon addition of NO3-, whereas NH4+ caused
      only minor fluctuations in these pools. The response of C. reinhardtii to NO3-
      indicates that the oxidative pentose phosphate pathway was activated to oxidize
      carbon upon the onset of NO3- assimilation, whereas reduction of carbon via the
      reductive pentose phosphate pathway was inhibited. This demonstrates a possible
      role for the Fd-thioredoxin system in coordinating enzyme activity in response to
      the metabolic demands for reducing power and carbon during NO3- assimilation.

PMID- 12232265
TI  - Ultraviolet-B-Responsive Anthocyanin Production in a Rice Cultivar Is Associated
      with a Specific Phase of Phenylalanine Ammonia Lyase Biosynthesis.
AB  - Seedlings of 17 rice (Oryza sativa L.) cultivars were classified on the basis of
      anthocyanin pigmentation into three groups: an acyanic group with 9 cultivars, a
      moderately cyanic group with 5 cultivars, and a cyanic group with 3 cultivars.
      Seedlings of the cyanic group were deep purple in color, possessing copious
      amounts of anthocyanin in shoots. Sunlight (SL)-mediated anthocyanin and
      phenylalanine ammonia lyase (PAL) induction in a cyanic cultivar, purple puttu,
      was compared with an acyanic cultivar, black puttu. A brief exposure of dark
      grown purple puttu seedlings to SL induced anthocyanin formation during a
      subsequent dark period with a peak at 24 h. The magnitude of SL-mediated
      anthocyanin induction is age dependent, the 4-d-old seedlings being the most
      responsive to SL. The anthocyanin induction in purple puttu seedlings is mediated
      exclusively by the ultraviolet-B (UV-B) component of SL. The SL-triggered
      anthocyanin induction was reduced by about 30% by a terminal far-red light pulse
      and was restored by a red light pulse, indicating the role of phytochrome in
      modulation of anthocyanin level. The SL-mediated induction of PAL showed two
      peaks, one at 4 h and the other at 12 h. Whereas the first PAL peak (4 h) was
      induced by phytochrome and was seen in both cultivars, the second PAL peak (12 h)
      was inducible by UV-B only in the cyanic purple puttu cultivar.

PMID- 12232266
TI  - Purification of a Membrane-Bound UDP-Glucose:Sterol [beta]-D-Glucosyltransferase
      Based on Its Solubility in Diethyl Ether.
AB  - Membrane-bound UDP-glucose:sterol [beta]-D-glucosyltransferase (UDPG-SGTase)
      catalyzes the formation of steryl glucosides from UDP-glucose and free sterols.
      This enzyme was purified from etiolated oat shoots (Avena sativa L. cv Alfred) in
      five steps. UDPG-SGTase was solubilized from a microsomal fraction with the
      detergent n-octyl-[beta]-D-thioglucopyranoside and then extracted into diethyl
      ether. Subsequent removal of the organic solvent, resolubilization with an
      aqueous buffer, and two column chromatographic steps on Q-Sepharose and Blue
      Sepharose resulted in a 12,500-fold overall purification. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of the final preparation revealed a 56-kD
      protein band, the intensity of which correlated with enzyme activity in the
      respective fractions. Polyclonal antibodies raised against this 56-kD protein did
      not inhibit enzyme activity but specifically bound to the native UDPG-SGTase.
      These results suggest that the 56-kD protein represents the UDPG-SGTase. The
      purified enzyme was specific for UDP-glucose (Km = 34 [mu]M), for which UDP was a
      competitive inhibitor (inhibitor constant = 47 [mu]M). In contrast to the
      specificity with regard to the glycosyl donor, UDPG-SGTase utilized all tested
      sterol acceptors, such as [beta]-sitosterol, cholesterol, stigmasterol, and
      ergosterol.

PMID- 12232267
TI  - Ozone-Induced Expression of Stress-Related Genes in Arabidopsis thaliana.
AB  - Ozone is a major gaseous pollutant that is known to have detrimental effects on
      plant growth and metabolism. We have investigated the effects of ozone on
      Arabidopsis thaliana growth and the pattern of expression of several stress
      related genes. A. thaliana plants treated with either 150 or 300 parts per
      billion (ppb) ozone daily for 6 h exhibited reduced growth and leaf curling.
      Fresh and dry weights of ozone-treated plants were reduced 30 to 48% compared to
      ambient air controls. RNA blot analyses demonstrated that mRNA levels for
      glutathione S-transferase (GST), phenylalanine ammonia-lyase (PAL), a neutral
      peroxidase, and a cytosolic Cu/Zn superoxide dismutase (SOD) were higher in
      plants treated with 300 ppb ozone than in ambient air-treated controls. The mRNA
      levels of lipoxygenase and a catalase were not affected by ozone treatment. Of
      the transcripts examined, GST mRNA levels increased the most, showing a 26-fold
      induction 3 h after the initiation of ozone treatment. PAL mRNA was also rapidly
      induced, reaching 3-fold higher levels than controls within 3 h of ozone
      treatment. The neutral peroxidase and SOD mRNA levels rose more slowly, with both
      reaching maximum levels corresponding to 5-fold and 3-fold induction,
      respectively, approximately 12 h after ozone treatment. These studies indicate
      that ozone-induced expression of stress-related genes in A. thaliana provides an
      excellent model system for investigating the molecular and genetic basis of ozone
      induced responses in plants.

PMID- 12232268
TI  - 5-enol-Pyruvyl-Shikimate-3-Phosphate Synthase from Zea mays Cultured Cells
      (Purification and Properties).
AB  - The shikimate pathway enzyme 5-enol-pyruvyl-shikimate-3-phosphate (EPSP) synthase
      (3-phosphoshikimate-1-carboxyvinyl transferase, EC 2.5.1.19) was purified from
      cultured maize (Zea mays L. var Black Mexican Sweet) cells. Homogeneous enzyme
      preparations were obtained by a four-step procedure using ammonium sulfate
      fractionation, anion- and cation-exchange chromatography, and substrate elution
      from a cellulose phosphate column. The last step resulted in two well-separated
      activities of about the same molecular weight. A 2000- to 3000-fold purification,
      with an overall recovery of one-fourth of the initial activity, was achieved.
      Both EPSP synthase isoforms were characterized with respect to structural,
      kinetic, and biochemical properties. Only slight differences are seen in
      molecular mass, activation energy, and apparent affinities for the two
      substrates. A more pronounced difference was found between their thermal
      inactivation rates. Two EPSP synthase isoforms were also elucidated in crude
      homogenates by anion-exchange fast protein liquid chromatography. This allowed us
      to follow their expression during a culture growth cycle. One form was found at
      substantial levels throughout, whereas the other increased in exponentially
      growing cells and declined in late-logarithmic phase. The analysis of highly
      purified plastid preparations demonstrated a plastidial localization of both
      proteins. Possible functional roles for maize EPSP synthase isozymes, with regard
      to the dual-pathway hypothesis and to the recent findings on defense-related
      aromatic biosynthesis in higher plants, are discussed.

PMID- 12232269
TI  - Regulation of Photosynthetic Induction State by the Magnitude and Duration of Low
      Light Exposure.
AB  - This study was undertaken to examine the dependence of the regulatory enzymes of
      photosynthetic induction on photon flux density (PFD) exposure in soybean
      (Glycine max L.). The induction state varies as a function of both the magnitude
      and duration of the PFD levels experienced prior to an increase in PFD. The
      photosynthetic induction state results from the combined activity of separate
      processes that each in turn depend on prior PFD environment in different ways.
      Direct measurement of enzyme activities coupled with determination of in situ
      metabolite pool sizes indicated that the fast-induction component was associated
      with the activation state of stromal fructose-1,6-bisphosphatase (FBPase, EC
      3.1.3.11) and showed rapid deactivation in the dark and at low PFD. The fast
      induction component was activated at low PFD levels, around 70 [mu]mol photons m
      2 s-1. Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco, EC 2.7.1.19)
      deactivated very slowly in the dark and required higher PFD for activation. Both
      enzymes saturated at lower PFD than did photosynthesis, around 400 [mu]mol
      photons m-2 s-1. Ribulose-5-phosphate kinase (EC 2.7.1.19) appeared never to be
      limiting to photosynthesis, and saturated at much lower PFD than either FBPase or
      Rubisco. Determination of photosynthetic metabolite pool sizes from leaves at
      different positions within a soybean canopy showed a limitation to carbon uptake
      at the stromal FBPase and possibly the sedoheptulose-1,7-bisphosphatase (EC
      3.1.3.37) in shade leaves upon initial illumination at saturating PFD levels.

PMID- 12232270
TI  - Iron-Deficiency Stress Responses in Cucumber (Cucumis sativus L.) Roots (A
      Possible Role for Ethylene?).
AB  - Most dicotyledonous species respond to Fe deficiency by developing several
      mechanisms known as Fe-deficiency stress responses. To study the regulation of
      these responses, young cucumber plants (Cucumis sativus L. cv Ashley) were grown
      in nutrient solution for 11 d, being deprived of Fe during the last 4 or 5 d.
      Inhibitors of ethylene synthesis (2 or 10 [mu]M aminoethoxyvinylglycine; 10 or 20
      [mu]M aminooxyacetic acid; 1, 2, 5, or 10 [mu]M Co2+ as CoCl2) or action (50,
      200, or 800 [mu]M Ag+ as silver thiosulfate) were added to the nutrient solution
      at different times during this period of growth with no Fe. After this period,
      the reduction of Fe3+ ethylenedi-aminetetraacetate by the roots of entire plants
      was measured with ferrozine by reading the absorbance at 562 nm after 2 h. The
      presence of the ethylene inhibitors in the nutrient solution inhibited the Fe
      deficiency stress responses ferric-reducing capacity and subapical root swelling.
      In another experiment, the addition of 1 [mu]M 1-aminocyclopropane-1-carboxylic
      acid (ACC), a precursor of ethylene synthesis, to the nutrient solution of plants
      having low ferric-reducing activity increased notably the ferric-reducing
      capacity and subapical root swelling. Here we show evidence that ethylene plays a
      role in the development of Fe-deficiency stress responses, since when ethylene
      synthesis or action was inhibited, the responses were also inhibited, and when a
      precursor of ethylene (ACC) was added, the responses were increased.

PMID- 12232271
TI  - A Nitrogen-Fixing Endophyte of Sugarcane Stems (A New Role for the Apoplast).
AB  - The intercellular spaces of sugarcane (Saccharum officinarum L.) stem parenchyma
      are filled with solution (determined by cryoscanning microscopy), which can be
      removed aseptically by centrifugation. It contained 12% sucrose (Suc; pH 5.5.)
      and yielded pure cultures of an acid-producing bacterium (approximately 104
      bacteria/mL extracted fluid) on N-poor medium containing 10% Suc (pH 5.5). This
      bacterium was identical with the type culture of Acetobacter diazotrophicus, a
      recently discovered N2-fixing bacterium specific to sugarcane, with respect to
      nine biochemical and morphological characteristics, including acetylene reduction
      in air. Similar bacteria were observed in situ in the intercellular spaces. This
      demonstrates the presence of an N2-fixing endophyte living in apoplastic fluid of
      plant tissue and also that the fluid approximates the composition of the
      endophytes's optimal culture medium. The apoplastic fluid occupied 3% of the stem
      volume; this approximates 3 tons of fluid/ha of the crop. This endogenous culture
      broth consisting of substrate and N2-fixing bacteria may be enough volume to
      account for earlier reports that some cultivars of sugarcane are independent of N
      fertilizers. It is suggested that genetic manipulation of apoplastic fluid
      composition may facilitate the establishment of similar symbioses with endophytic
      bacteria in other crop plants.

PMID- 12232272
TI  - Effect of Aerobic Priming on the Response of Echinochloa crus-pavonis to
      Anaerobic Stress (Protein Synthesis and Phosphorylation).
AB  - Echinochloa species differ in their ability to germinate and grow in the absence
      of oxygen. Seeds of Echinochloa crus-pavonis (H.B.K.) Schult do not germinate
      under anoxia but remain viable for extended periods (at least 30 d) when
      incubated in an anaerobic environment. E. crus-pavonis can be induced to
      germinate and grow in an anaerobic environment if the seeds are first subjected
      to a short (1-18 h) exposure to aerobic conditions (aerobic priming). Changes in
      polypeptide patterns (constitutive and de novo synthesized) and protein
      phosphorylation induced by aerobic priming were investigated. In the absence of
      aerobic priming protein degradation was not evident under anaerobic conditions,
      although synthesis of a 20-kD polypeptide was induced. During aerobic priming,
      however, synthesis of 37- and 55-kD polypeptides was induced and persisted upon
      return of the seeds to anoxia. Furthermore, phosphorylation of two 18-kD
      polypeptides was observed only in those seeds that were labeled with 32PO4 during
      the aerobic priming period. Subsequent chasing in an anaerobic environment
      resulted in a decrease in phosphorylation of these polypeptides. Likewise,
      phosphorylation of the 18-kD polypeptides was not observed if the seeds were
      labeled in an anaerobic atmosphere. These results suggest that the regulated
      induction of the 20-, 37-, and 55- kD polypeptides may be important for anaerobic
      germination and growth of E. crus-pavonis and that the specific phosphorylation
      of the 18-kD polypeptides may be a factor in regulating this induction.

PMID- 12232273
TI  - Nitrogen Source Regulation of Growth and Photosynthesis in Beta vulgaris L.
AB  - Sugar beets (Beta vulgaris L. cv F58-554H1) were grown hydroponically in a 16-h
      light, 8-h dark period at a photosynthetic photon flux density of 0.5 mmol m-2 s
      1 for 4 weeks in half-Hoagland culture solution containing only nitrate-nitrogen.
      Half of the plants were then transferred to half-Hoagland solution with ammonium
      nitrogen (7.35mM), while the other half continued on 7.5 mM nitrate. Growth
      analysis was carried out by sampling the plants at 3-d intervals over a period of
      21 d. Compared to plants supplied with nitrate, ammonium initially slowed the
      growth of shoots more than roots. Ammonium reduced both the area expansion of
      individual leaves and the relative water content of these leaves, but increased
      the amount of dry matter/area. The increase in specific leaf weight in ammonium
      grown leaves was associated with a doubling of chloroplast volume, as much as a
      62% rise in chlorophyll content, and a 4.3-fold higher accumulation of soluble
      protein. Ammonium nutrition substantially decreased the rate of expansion of
      photosynthetic (leaf) surface but did not decrease the rate of photosynthesis per
      area; in fact, net photosynthetic CO2 exchange rates were slightly higher than in
      nitrate plants, due to the build-up in stromal enzymes of the Calvin cycle,
      several of which increased in total extractable activity on a leaf area basis,
      e.g. ribulose-1,5- biphosphate carboxylase oxygenase, sedoheptulose-1,7
      biphosphatase. Nitrogen source had no effect on stomatal conductance. Rates of
      photosynthesis per chlorophyll were decreased slightly in ammonium-grown leaves,
      possibly due to an increased CO2-diffusion resistance associated with the
      enlarged chloroplasts.

PMID- 12232274
TI  - Differential Expression of the Two Subunits of Tomato Polygalacturonase Isoenzyme
      1 in Wild-Type and rin Tomato Fruit.
AB  - The [beta] subunit of tomato (Lycopersicon esculentum Mill.) fruit
      polygalacturonase 1 is a cell wall glycoprotein that binds to and apparently
      regulates the catalytic PG2 polypeptide in vivo. [beta] Subunit and
      polygalacturonase 2 (PG2) expression have been investigated in both wild-type and
      ripening inhibitor (rin) mutant fruit. During fruit development and ripening,
      [beta] subunit expression was unrelated to expression of the catalytic PG2
      protein. In wild-type fruit, [beta] subunit mRNA and protein were first detected
      early in development and increased to maximal levels before PG2 mRNA and protein
      were detected. At the onset of ripening [beta] subunit mRNA decreased
      dramatically, but [beta] subunit protein levels remained stable. In rin fruit,
      which fail to ripen, [beta] subunit expression was similar to that in wild type,
      although PG2 mRNA and protein were not detected. These data suggest that [beta]
      subunit expression is ethylene independent and regulated primarily by
      developmental cues. This conclusion is supported by results from ethylene-treated
      immature (20 days after pollination) wild-type and rin fruit in which no
      significant differences were observed in [beta] subunit expression patterns in
      response to ethylene treatment. Surprisingly, RNA blot analysis indicated that
      catalytic PG2 mRNA was induced in immature rin fruit after 3 d of exogenous
      ethylene treatment. In addition, [beta] subunit mRNA and protein were also
      detected at lower levels in root, leaf, and flower tissues of both genotypes,
      suggesting a broader functional role for the protein.

PMID- 12232275
TI  - Carbonic Anhydrase Activity in Isolated Chloroplasts of Wild-Type and High-CO2
      Dependent Mutants of Chlamydomonas reinhardtii as Studied by a New Assay.
AB  - In an assay of carbonic anhydrase (CA), NAH14CO3 soltution at the bottom of a
      sealed vessel releases 14CO2, which diffuses to the top of the vessel to be
      assimilated by photosynthesizing Chlamydomonas reinhardtii cells that have been
      adapted to a low-CO2 environment. The assay is initiated by illuminating the
      cells and is stopped by turning the light off and killing the cells with acid.
      Enzyme activity was estimated from acid-stable radioactivity. With bovine CA, 1.5
      Wilbur-Anderson units (WAU) was consistently measured at 5- to 6-fold above
      background. Sonicated whole cells of air-adapted wild-type C. reinhardtii had 740
      [plus or minus] 12.4 WAU/mg chlorophyll (Chl). Sonicated chloroplasts from a
      mixotrophically grown wall-less strain, cw-15, had 35.5 [plus or minus] 2.6
      WAU/mg Chl, whereas chloroplasts from wall-less external CA mutant strain cia5/cw
      15 had 33.8 [plus or minus] 1.9 WAU/mg Chl. Sonicated chloroplasts from the wall
      less mutant strain cia-3/cw-15, believed to lack an internal CA, had 2.8 [plus or
      minus] 3.2 WAU/mg Chl. Sonicated whole cells from cia3/cw-15 had 2.8 [plus or
      minus] 7.8 WAU/mg Chl. Acetazolamide, ethoxyzolamide, and p-aminomethylbenzene
      sulfonamide (Mafenide) at 100 [mu]M inhibited CA in sonicated chloroplasts from
      cia-5/cw-15. Treatment at 80[deg]C for 10 min inhibited this CA activity by 90.8
      [plus or minus] 3.6%. Thus, a sensitive 14C assay has confirmed the presence of a
      CA in cw-15 and cia-5/cw-15 chloroplasts and the lack of a CA in cia-3/cw-15
      chloroplasts. Our results indicate that HCO3- is the inorganic carbon species
      that is accumulated by chloroplasts of Chlamydomonas and that chloroplastic CA is
      responsible for the majority of internal CA activity.

PMID- 12232276
TI  - Maternal Effects Govern Variable Dominance of Two Abscisic Acid Response
      Mutations in Arabidopsis thaliana.
AB  - Three abscisic acid (ABA)-controlled responses (seed dormancy, inhibition of
      germination by applied ABA, and stomatal closure) were compared in wild-type
      versus homo- and heterozygotes of two Arabidopsis thaliana ABA-insensitive
      mutants, abi1 and abi2. We found that sensitivity of seeds to applied ABA is
      partially maternally controlled but that seed dormancy is determined by the
      embryonic genotype. The effects of the abi1 and abi2 mutations on ABA sensitivity
      of seed germination ranged from recessive to nearly fully dominant, depending on
      the parental source of the mutant allele. This maternal effect disappeared during
      vegetative growth. Stomatal regulation in heterozygotes showed substantial
      variability, but the average water loss was intermediate between that of
      homozygous mutants and wild type.

PMID- 12232277
TI  - Expression of Early Light-Inducible Proteins in Flag Leaves of Field-Grown
      Barley.
AB  - Early light-inducible protein (ELIP) mRNA and protein levels were analyzed during
      maturation and senescence of barley (Hordeum vulgare L.) flag leaves under field
      conditions. The data clearly demonstrate that ELIP mRNA levels are related to the
      sunlight intensity before sample collection. Levels of mRNAs encoding both low
      and high molecular mass ELIPs fluctuate in parallel. Changes in mRNA levels are
      accompanied by corresponding changes in protein levels except for days when
      average temperatures are high. Comparison of flag leaves at different stages of
      development in spring and winter barley varieties suggests that light-stress
      regulated ELIP gene expression is independent of the developmental stage of the
      leaves. Although chlorophyll content, photosystem II (PSII) efficiency, and 32-kD
      herbicide-binding protein of PSII levels decrease drastically after the onset of
      senescence, ELIP mRNA and protein still accumulate to high levels on bright days.

PMID- 12232278
TI  - Transcriptional and Posttranscriptional Regulation of Nitrogen-Responding
      Expression of Phosphoenolpyruvate Carboxylase Gene in Maize.
AB  - To study the regulation of gene expression for enzymes in the C4 photosynthetic
      pathway of maize (Zea mays L.) in response to changing N status in developing
      photosynthetic cells, we have studied in vitro transcription of the
      phosphoenolpyruvate carboxylase (PEPC) gene in leaf nuclei isolated from plants
      during recovery from N starvation. The induction was specific for the C4-type
      PEPC gene (C4Ppc1), and its transcription was N dependent and increased markedly
      by supply of an N source, but there was a discrepancy between the steady-state
      levels of mRNA and the stimulation of in vitro transcription. The results suggest
      that the N-inducible expression of C4Ppc1 is regulated both transcriptionally and
      posttranscriptionally by N availability. The in vitro transcription rate of
      C4Ppc1 was greatly stimulated by incubating detached leaves with zeatin alone,
      whereas the rate remained essentially unchanged by incubating with an exogenous N
      source alone. The results, taken together, imply that cytokinins up-regulate the
      transcription of C4Ppc1 in response to N status, whereas glutamine and/or its
      metabolite(s) up-regulate the level of the transcript. The transcription was
      totally inhibited by cycloheximide, indicating that the cytokinin-dependent
      transcription of C4Ppc1 requires the synthesis of protein.

PMID- 12232279
TI  - Effects of Growth Temperature on the Responses of Ribulose-1,5-Biphosphate
      Carboxylase, Electron Transport Components, and Sucrose Synthesis Enzymes to Leaf
      Nitrogen in Rice, and Their Relationships to Photosynthesis.
AB  - Effects of growth temperature on the photosynthetic gas-exchange rates and their
      underlying biochemical properties were examined in young, fully expanded leaves
      of rice (Oryza sativa L.). The plants were grown hydroponically under day/night
      temperature regimes of 18/15[deg]C, 23/18[deg]C, and 30/23[deg]C and all
      photosynthetic measurements were made at a leaf temperature of 25[deg]C and an
      irradiance of 1800 [mu]mol quanta m-2 s-1. Growth temperature affected the
      photosynthetic CO2 response curve. The relative ratio of the initial slope to the
      CO2-saturated photosynthesis increased with rising growth temperature. This was
      caused mainly by an increase in CO2-limited photosynthesis for a given leaf
      nitrogen content with rising growth temperature. However, there was no difference
      in ribulose-1,5-bisphosphate carboxylase (Rubisco) content at any given leaf
      nitrogen content among temperature treatments. In addition, the activation state
      and catalytic turnover rate of Rubisco were not affected by growth temperature.
      The increase in CO2-limited photosynthesis with rising growth temperature was the
      result of an increase in the CO2 transfer conductance between the intercellular
      airspaces and the carboxylation sites. The amounts of total chlorophyll and light
      harvesting chlorophyll a/b protein II increased for the same leaf nitrogen
      content with rising growth temperature, but the amounts of cytochrome f and
      coupling factor 1 and the activities of cytosolic fructose-1,6-bisphosphatase and
      sucrose-phosphate synthase were the same between plants grown at 23/18[deg]C and
      those grown at 30/23[deg]C. Similarly, CO2-saturated photosynthesis was not
      different for the same leaf nitrogen content between these treatments. For the
      18/15[deg]C-grown plants, a slight decrease in the amounts of cytochrome f and
      coupling factor 1 and an increase in the activities of cytosolic fructose-1,6
      bisphosphatase and sucrose-phosphate synthase were found, but these were not
      reflected in CO2-saturated photosynthesis.

PMID- 12232280
TI  - Chemically Induced Cuticle Mutation Affecting Epidermal Conductance to Water
      Vapor and Disease Susceptibility in Sorghum bicolor (L.) Moench.
AB  - Analysis of Sorghum bicolor bloomless (bm) mutants with altered epicuticular wax
      (EW) structure uncovered a mutation affecting both EW and cuticle deposition. The
      cuticle of mutant bm-22 was about 60% thinner and approximately one-fifth the
      weight of the wild-type parent P954035 (WT-P954035) cuticles. Reduced cuticle
      deposition was associated with increased epidermal conductance to water vapor.
      The reduction in EW and cuticle deposition increased susceptibility to the fungal
      pathogen Exserohilum turcicum. Evidence suggests that this recessive mutation
      occurs at a single locus with pleiotropic effects. The independently occurring
      gene mutations of bm-2, bm-6, bm-22, and bm-33 are allelic. These chemically
      induced mutants had essentially identical EW structure, water loss, and cuticle
      deposition. Furthermore, 138 F2 plants from a bm-22 x WT-P954035 backcross showed
      no recombination of these traits. This unique mutation in a near-isogenic
      background provides a useful biological system to examine plant cuticle
      biosynthesis, physiology, and function.

PMID- 12232281
TI  - A Low Molecular Mass Heat-Shock Protein Is Localized to Higher Plant
      Mitochondria.
AB  - When pea (Pisum sativum L. var Douce Provence) plants are shifted from a normal
      growth temperature of 25[deg] C up to 40[deg] C for 3 h, a novel 22-kD protein is
      produced and accumulates in the matrix compartment of green leaf mitochondria.
      HSP22 was purified and used as antigen to prepare guinea pig antiserum. The
      expression of HSP22 was studied using immunodetection methods. HSP22 is a nuclear
      encoded protein de novo synthesized in heat-stressed pea plants. The heat-shock
      response is rapid and can be detected as early as 30 min after the temperature is
      raised. On the other hand, HSP22 declines very slowly after pea leaves have been
      transferred back to 25[deg] C. After 100 h at 25[deg] C, the heat-shock pattern
      was undetectable. The precise localization of HSP22 was investigated and we
      demonstrated that HSP22 was found only in mitochondria, where it represents 1 to
      2% of total matrix proteins. However, the induction of HSP22 does not seem to be
      tissue specific, since the protein was detected in green or etiolated pea leaves
      as well as in pea roots. Finally, examination of matrix extracts by nondenaturing
      polyacrylamide gel electrophoresis and immunoblotting with anti-HSP22 serum
      revealed a high-molecular mass heat-shock protein complex of 230 kD, which
      contains HSP22.

PMID- 12232282
TI  - High Mitochondrial Activity but Incomplete Engagement of the Cyanide-Resistant
      Alternative Pathway in Guard Cell Protoplasts of Pea.
AB  - The respiratory properties of guard cell protoplasts (GCP) were examined in
      comparison with those of mesophyll protoplasts (MCP) from the same leaves of pea
      (Pisum sativum L. cv Arkel). The rates of respiratory O2 uptake by GCP were
      extremely high (280 [mu]mol mg-1 Chl h-1) and were several times greater than
      those of MCP. On the other hand, the rates of photosynthetic O2 evolution by GCP
      were similar to those of MCP. Also on the basis of protoplast volume, the
      respiratory rates of GCP were higher: more than three times those of MCP. The
      enzymes of the tricarboxylic acid cycle, per unit protein or unit protoplast
      volume, had a 2- to 5-fold higher activity in GCP than in MCP, indicating an
      enrichment of mitochondrial activity in GCP relative to that in MCP. Respiratory
      inhibitors were used to assess the activity of the cytochrome (cyanide-sensitive)
      and alternative (cyanide-resistant) pathways in GCP and MCP. The inhibition of
      respiration by KCN or antimycin A was more in GCP than that in MCP. The marked
      inhibition of respiratory O2 uptake by salicylhydroxamic acid in the presence of
      KCN showed the presence of the cyanide-resistant pathway in GCP. The activity of
      the cyanide-resistant electron transport path constituted only one-third of total
      respiration in GCP but accounted for two-thirds of respiration in MCP. The
      alternative pathway was not completely engaged in GCP but reached its full
      capacity in MCP.

PMID- 12232283
TI  - Biosynthesis of Phosphatidylglycerol in Isolated Mitochondria of Etiolated Mung
      Bean (Vigna radiata L.) Seedlings.
AB  - Phosphatidylglycerophosphate synthase (sn-glycerol-3-phosphate:CDP-diacylglycerol
      phosphatidyltransferase) and phosphatidylglycerophosphate phosphatase were
      characterized in mung bean (Vigna radiata L.) mitochondria. The synthase has a
      rather broad pH optimum between 7 and 9, whereas the phosphatase has one of about
      7. Both enzymic activities are stimulated by Triton X-100 and require divalent
      cations but differ in their cation specificities. The synthase shows apparent Km
      values of 9 and 3 [mu]M for sn-glycerol-3-phosphate and CDP-diacylglycerol,
      respectively. Phosphatidylglycerophosphate, in contrast to lysophosphatidic and
      phosphatidic acid, is effectively dephosphorylated by the phosphatase, which
      exhibits an apparent Km value of 12 [mu]M for its substrate. Each enzyme shows
      higher activities with the dipalmitoyl species of its substrate than with the
      dioleoyl species. These substrate specificities of both enzymes are predominantly
      based on differences in apparent Vmax values.

PMID- 12232284
TI  - Purification of the Fusicoccin-Binding Protein from Oat Root Plasma Membrane by
      Affinity Chromatography with Biotinylated Fusicoccin.
AB  - Fusicoccin (FC), a fungal phytotoxin, evokes a number of physiological responses
      after binding to the FC-binding protein (FCBP). For characterization of this
      plasma membrane protein and elucidation of the signal transduction pathway, we
      purified active FCBP from oat (Avena sativa L. cv Valiant) root plasma membranes
      using avidin-biotin affinity chromatography. For the binding of FCBP to
      immobilized avidin, a bifunctional FC derivative (FC-biotin, FCBio) was
      synthesized. FCBio retained high binding affinity for the FCBP (KD = 70 nM), it
      elicited a biological response comparable to FC, and it was bound by avidin. The
      purification of the FCBP involved three important steps. First, FCBio was bound
      to the FCBP in purified plasma membrane vesicles. Next, plasma membrane proteins
      were solubilized in detergent, and part of the solubilized proteins was
      precipitated by decreasing the detergent concentration below the critical micelle
      concentration. The FCBP remained in the soluble fraction, and this fraction was
      loaded on a "low-affinity" avidin column. Proteins, bound through a biotin moiety
      to the column, were specifically eluted with excess biotin. This resulted in
      fractions active in [3H]FC binding and two bands on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of 31 and 30 kD. The nonhydrophobic behavior
      of the FCBP was confirmed by means of phase separation with Triton X-114, wherein
      the FCBP migrated to the hydrophilic phase. Purification of the FCBP in active
      form using this novel affinity technique opens the possibility to study other
      features of the FCBP necessary for inducing physiological responses in plant
      cells.

PMID- 12232285
TI  - An Early Indicator of Resistance in Barley to Russian Wheat Aphid.
AB  - During early stages of infestation by Russian wheat aphids (Diuraphis noxia
      [Mordvilko]; RWAs), barley (Hordeum vulgare L.) leaf cells collapsed and showed
      autofluorescence in the mesophyll and bundle sheath adjacent to the RWA stylet
      sheath. The response was visually similar to the hypersensitive cell death
      response, typical of resistance to microbial pathogens. Resistant barley produced
      significantly more collapsed, autofluorescent cells (CAC) than did susceptible
      barley. RWA stylet entry sites and sheath paths also fluoresced, making them easy
      to observe in whole leaf sections. The number of CAC increased with the number of
      RWAs and with the number of days of feeding in resistant plants. The CAC could be
      observed 1 d following infestation, making this the most rapid plant response
      toward the RWAs known to date. The response may be useful in screening for
      resistant plants and may provide insight into resistance mechanisms in barley.

PMID- 12232286
TI  - Chlorophyll Biosynthetic Reactions during Senescence of Excised Barley (Hordeum
      vulgare L. cv IB 65) Leaves.
AB  - The chlorophyll (Chl) biosynthetic reactions were monitored during senescence of
      dark-incubated excised barley (Hordeum vulgare L. cv IB 65) leaves floated in
      double-distilled water or kinetin solution. Kinetin abolished the degradation of
      Chl but failed to check the net degradation of protochlorophyllide (Pchlide),
      suggesting that different sets of enzymes, i.e. kinetin sensitive and
      insensitive, are responsible for the degradation of Chl and Pchlide,
      respectively. Upon exposure of the leaves to light, the dark-accumulated Pchlide
      was efficiently phototransformed to chorophyllide (Chlide), even on the 7th d of
      dark incubation, demonstrating that the activity of Pchlide reductase, one of the
      late enzymes of the Chl biosynthetic pathway, is not substantially affected
      during senescence. The senescing leaves continued to synthesize Pchlide and
      Chlide until the 7th d, although at a reduced rate (20% of the 1st d). The
      decline of the rate of synthesis of Pchlide and Chlide is due to the loss of
      activity of two early enzymes of the Chl biosynthetic pathway, i.e. 5
      aminolevulinic acid dehydratase and porphobilinogen deaminase. Kinetin
      substantially checked the loss of activity of these two enzymes.

PMID- 12232287
TI  - A Re-Evaluation of the Role of the Infected Cell in the Control of O2 Diffusion
      in Legume Nodules.
AB  - Two different simulation models were constructed to describe O2 diffusion into
      the bacteria-infected cells of legume nodules: one based on a central zone of
      uniform spherical cells and the other on a central zone of packed, uniform
      cubical cells with air spaces along the edges. The cubical model more closely
      approximated the geometry and gas diffusion characteristics of infected cells
      than did the spherical model. The models relied on set values for the innermost
      O2 concentration in the infected cell (1-20 nM) and predicted values for the free
      O2 and oxygenated leghemoglobin gradients toward the cell:space interface. The
      cubical model but not the spherical model predicted saturation of leghemoglobin
      (Lb) oxygenation at or within a few micrometers of the gas-filled intercellular
      space and predicted that the space concentration could be as high as 1.3% O2 when
      the fractional oxygenation of Lb and respiration rate within the infected cell
      were typical of that which has been measured in vivo. In the model, the higher
      the space O2 concentration, the greater the saturation of Lb by O2 and the
      greater the collapse of Lb-facilitated diffusion near the cell:space interface.
      This was predicted to result in a greater resistance to O2 diffusion from the
      space to the bacteroids, thereby providing an intrinsic, homeostatic mechanism
      for controlling the rate of O2 influx into infected cells. Changes in the
      physiological features of the simulated cubical infected cell, such as the
      proportion of the cell as cytosol, the surface area of the cell exposed to a
      space, the maximum rate of cellular respiration, or the concentration of Lb in
      the cytoplasm, significantly altered the extent to which the infected cell would
      be able to regulate its diffusive resistance. These results demonstrate the
      possibility of a Lb-based mechanism for controlling the O2 concentration within
      the infected cells. If such a mechanism exists in legume nodules, it would give
      the infected cell an ability to exercise fine control over its internal
      environment, a process that could complement a physical diffusion barrier that
      may exist in the inner cortex or elsewhere in the nodule and provide coarse
      control over O2 diffusion.

PMID- 12232288
TI  - Metabolism of the Raffinose Family Oligosaccharides in Leaves of Ajuga reptans L.
      (Cold Acclimation, Translocation, and Sink to Source Transition: Discovery of
      Chain Elongation Enzyme).
AB  - Ajuga reptans is a frost-hardy, perennial labiate that is known for its high
      content of raffinose family oligosaccharide(s) (RFO). Seasonal variations in
      soluble nonstructural carbohydrate levels in above-ground parts of Ajuga showed
      that the RFO were by far the most predominant components throughout the whole
      year. RFO were lowest in summer (75 mg/g fresh weight) and highest in fall/winter
      (200 mg/g fresh weight), whereas sucrose and starch were only minor components.
      Cold treatment (14 d at 10/3[deg]C, day/night) of plants that were precultivated
      under warm conditions (25[deg]C) lowered the temperature optimum of net
      photosynthesis from 16[deg] to 8[deg]C, decreased the maximum rate, and increased
      the total nonstructural carbohydrate content of leaves by a factor of about 10,
      mainly because of an increase of RFO. The degree of polymerization of the RFO
      increased sequentially up to at least 15. A novel, galactinol-independent
      galactosyltransferase enzyme was found, forming from two molecules of RFO, the
      next higher and lower degree of polymerization of RFO. The enzyme had a pH
      optimum of 4.5 to 5.0 and may be responsible for RFO chain elongation. RFO were
      the main carbohydrates translocated in the phloem, with stachyose being by far
      the most dominant form. Studies of carbon balance during leaf development
      revealed a transition point between import and export at approximately 25%
      maximal leaf area. RFO synthesis could be detected even before the commencement
      of export, suggesting the existence of a nonphloem-linked RFO pool even in very
      young leaves. Taken together, it seems that Ajuga leaves contain two pools of RFO
      metabolism, a pronounced long-term storage pool in the mesophyll, possibly also
      involved in frost resistance, and a transport pool in the phloem.

PMID- 12232289
TI  - Changes in the Accumulation of [alpha]- and [beta]-Tubulin Isotypes during Cotton
      Fiber Development.
AB  - The expression of [alpha]- and [beta]-tubulin proteins in developing fibers and
      several other tissues of cotton (Gossypium hirsutum, cv Texas Marker 1) have been
      analyzed by immunoblots of one- and two-dimensional gels utilizing anti-tubulin
      antibodies as probes. As a percentage of total protein, fibers had greater
      amounts of tubulin than did hypocotyls, roots, leaves, or cotyledons. Both
      [alpha]- and [beta]-tubulin, having apparent molecular masses of approximately 50
      kD and isoelectric points between pH 5 and pH 6, were resolved on a single two
      dimensional gel. Under the conditions used, [alpha]-tubulin was less acidic in
      the isoelectric focusing dimension and migrated slightly faster in the sodium
      dodecyl sulfate dimension than did [beta]-tubulin. Nine [alpha]-tubulin isotypes
      that formed two distinct groups were identified on immunoblots of two-dimensional
      gels. The three most abundant [alpha]-tubulin isotypes were common to all tissues
      examined. Seven distinct [beta]-tubulin isotypes were also identified. Although
      their level of accumulation differed, four of the [beta]-tubulin isotypes were
      common to all tissues. Preferential accumulation of isotypes was more apparent in
      fibers than in the other tissues examined. Two [alpha]-tubulin isotypes and two
      [beta]-tubulin isotypes showed preferential accumulation in 10- and 20-d
      postanthesis fibers, respectively.

PMID- 12232290
TI  - The Role of Plastids in the Expression of Nuclear Genes for Thylakoid Proteins
      Studied with Chimeric [beta]-Glucuronidase Gene Fusions.
AB  - We have analyzed plastid and nuclear gene expression in tobacco seedlings using
      the carotenoid biosynthesis inhibitor nor-flurazon. mRNA levels for three nuclear
      encoded chlorophyll-binding proteins of photosystem I and photosystem II (CAB I
      and II and the CP 24 apoprotein) are no longer detectable in photobleached
      seedlings, whereas those for other components of the thylakoid membrane (the 33-
      and 23-kD polypeptides and Rieske Fe/S polypeptide) accumulate to some extent.
      Transgenic tobacco seedlings with promoter fusions from genes for thylakoid
      membrane proteins exhibit a similar expression behavior: a CAB-[beta]
      glucuronidase (GUS) gene fusion is not expressed in herbicide-treated seedlings,
      whereas PC-, FNR-, PSAF-, and ATPC-promoter fusions are expressed, although at
      reduced levels. All identified segments in nuclear promoters analyzed that have
      been shown to respond to light also respond to photodamage to the plastids. Thus,
      the regulatory signal pathways either merge prior to gene regulation or interact
      with closely neighboring cis elements. These results indicate that plastids
      control nuclear gene expression via different and gene-specific cis-regulatory
      elements and that CAB gene expression is different from the expression of the
      other genes tested. Finally, a plastid-directing import sequence from the maize
      Waxy gene is capable of directing the GUS protein into the photodamaged
      organelle. Therefore, plastid import seems to be functional in photobleached
      organelles.

PMID- 12232291
TI  - Defense Responses in Infected and Elicited Cucumber (Cucumis sativus L.)
      Hypocotyl Segments Exhibiting Acquired Resistance.
AB  - Segments from dark-grown cucumber (Cucumis sativus L.) hypocotyls were used to
      study defense reactions occurring upon fungal infection and induced by elicitors
      in the same tissue. The segments were rendered resistant to infection by
      Colletotrichum lagenarium either by growing the seedlings in the presence of
      dichloroisonicotinic acid (DCIA) or by preincubation of the cut segments with
      DCIA, salicylic acid (SA), or 5-chlorosalicylic acid (5CSA). This resistance
      appears to be due mainly to inhibition of fungal penetration into epidermal
      cells. In the resistant hypocotyl segments, the fungus induced, at the time of
      attempted penetration, an increased deposition of phenolics, which were
      visualized by autofluorescence. These phenolics were located mainly in the
      epidermal cell wall around and in the emerging papillae below appressoria and
      were quantified either as lignin-like polymers by the thioglycolic acid method or
      as 4-OH-benzaldehyde, 4-OH-benzoic, or 4-coumaric acid liberated upon treatment
      with alkali at room temperature. Pretreatment with DCIA, SA, and 5CSA induced
      little chitinase activity, but this activity greatly increased in resistant
      tissues upon subsequent infection. These observations indicate that resistance is
      associated with an improved perception of the pathogen stimulus resulting in the
      enhanced induction of diverse defense reactions. When the cut segments were
      pretreated with DCIA, SA, or 5CSA and then split and incubated with chitosan
      fragments, the deposition of cell wall phenolics was also enhanced. These
      pretreated and split segments also exhibited an increase in the rapid production
      of activated oxygen species induced by an elicitor preparation from Phytophthora
      megasperma f. sp. Glya. Pretreatment of the segments with methyl jasmonate
      neither induced resistance nor enhanced induction of cell wall phenolics upon
      fungal infection, although we observed in the corresponding split segments some
      increase in chitosan-induced cell wall phenolics and in elicitor-induced rapid
      production of activated oxygen species.

PMID- 12232292
TI  - Catalase Is Differentially Expressed in Dividing and Nondividing Protoplasts.
AB  - Based on our previous results that peroxidase is induced in dividing tobacco
      protoplasts but it is not expressed in the nondividing grapevine (Vitis vinifera
      L.) protoplasts during culture (C.I. Siminis, A.K. Kanellis, K.A. Roubelakis
      Angelakis [1993] Physiol Plant 87: 263-270), we further tested the hypothesis
      that oxidative stress may be implicated in the recalcitrance of plant
      protoplasts. The expression of catalase, a major defense enzyme against cell
      oxidation, was studied during isolation and culture of mesophyll protoplasts from
      the recalcitrant grapevine and regenerating tobacco (Nicotiana tabacum L.).
      Incubation of tobacco leaf strips with cell wall-degrading enzymes resulted in a
      burst of catalase activity and an increase in its immunoreactive protein; in
      contrast, no such increases were found in grapevine. The cathodic and anodic
      catalase isoforms consisted exclusively of subunits [alpha] and [beta],
      respectively, in tobacco, and of subunits [beta] and [alpha], respectively, in
      grapevine. The catalase specific activity increased only in grapevine protoplasts
      during culture. The ratio of the enzymatic activities to the catalase
      immunoreactive protein declined in dividing tobacco protoplasts and remained
      fairly constant in nondividing tobacco and grapevine protoplasts during culture.
      Also, in dividing tobacco protoplasts the de novo accumulation of the catalase
      [beta] subunit gave rise to the acidic isoenzymes, whereas in nondividing tobacco
      and grapevine protoplasts, after 8 d in culture, only the basic isoenzymes
      remained due to de novo accumulation of the [alpha] subunit. The pattern of
      catalase expression in proliferating tobacco leaf cells during callogenesis was
      similar to that in dividing protoplasts. The different responses of catalase
      expression in dividing and nondividing tobacco and grapevine mesophyll
      protoplasts may indicate a specificity of catalase related to induction of
      totipotency.

PMID- 12232293
TI  - Seasonal Acclimation of Stem Photosynthesis in Woody Legume Species from the
      Mojave and Sonoran Deserts of California.
AB  - Photosynthesis (Pn) was measured in stems of two desert legumes, Caesalpinia
      virgata at a low elevation site (118 m) in the Sonoran Desert and Senna armata at
      a higher elevation (950 m) in the Mojave Desert. The lower elevation site
      experienced higher spring and summer temperatures than the higher elevation site,
      but the air vapor pressure, irradiance, and rainfall patterns were similar. Mid
      morning maximum stem Pn was highest in May for C. virgata (7.8 [mu]mol m-2 s-1)
      and in July for S. armata (5.8 [mu]mol m-2 s-1). The seasonal variation in
      maximum stem Pn was not associated with changes in bulk tissue water potential or
      chlorenchyma tissue nitrogen concentration. The main environmental regulators of
      seasonal stem Pn were temperature and leaf to air vapor pressure gradient. Light
      response curves indicated no major differences in apparent quantum yield or light
      compensation point between the spring and summer, but light-saturated stem Pn at
      ambient temperature decreased for C. virgata between these seasons. The optimal
      temperature for stem Pn remained the same for both species between the spring and
      the summer. However, stem Pn of both species increased at all temperatures
      between the spring and summer. Potential stem Pn under optimal conditions and CO2
      saturated stem Pn increased for both species between spring and summer. The
      increase in stem Pn potential allowed these species to maintain stem Pn during
      the summer even though stem Pn responses to temperature and vapor pressure did
      not acclimate to seasonal climatic conditions.

PMID- 12232294
TI  - Two Distinct Aldolases of Class II Type in the Cyanoplasts and in the Cytosol of
      the Alga Cyanophora paradoxa.
AB  - Two aldolases from the alga Cyanophora paradoxa (Glaucocystophyta) can be
      separated by chromatography on diethylaminoethyl-Fractogel. The two aldolases are
      inhibited by 1 mM ethylene-diaminetetraacetate (EDTA) and, therefore, are class
      II aldolases. When cells of C. paradoxa were fractionated, one aldolase was
      associated with the cytosol fraction and the other was associated with the
      cyanoplast fraction. The Km(fructose-1,6-bisphosphate) was 600 [mu]M for the
      cytosolic aldolase and 340 [mu]M for the cyanoplast aldolase. The activity of the
      cytosolic aldolase was increased up to 4-fold by 100 mM K+ and slightly inhibited
      by Li+ and Cs+, whereas the cyanoplast aldolase was not affected by these ions.
      Inactivation by 1 mM EDTA could be partly restored by the addition of Co2+ or
      Mn2+ and to a lesser extent by Zn2+ or Mg2+. The molecular masses of the native
      cytosolic and cyanoplast aldolases are about 90 and 85 kD, respectively, as
      estimated by velocity centrifugation in sucrose gradients. Implications for the
      evolution of class I and II aldolases in chloroplasts of higher plants and algae
      will be discussed.

PMID- 12232295
TI  - Inward-Rectifying K+ Channels in Root Hairs of Wheat (A Mechanism for Aluminum
      Sensitive Low-Affinity K+ Uptake and Membrane Potential Control).
AB  - K+ is the most abundant cation in cells of higher plants, and it plays vital
      roles in plant growth and development. Extensive studies on the kinetics of K+
      uptake in roots have shown that K+ uptake is mediated by at least two transport
      mechanisms, one with a high and one with a low affinity for K+. However, the
      precise molecular mechanisms of K+ uptake from soils into root epidermal cells
      remain unknown. In the present study we have pursued the biophysical
      identification and characterization of mechanisms of K+ uptake into single root
      hairs of wheat (Triticum aestivum L.), since root hairs constitute an important
      site of nutrient uptake from the soil. These patch-clamp studies showed
      activation of a large inward current carried by K+ ions into root hairs at
      membrane potentials more negative than -75 mV. This K+ influx current was
      mediated by hyperpolarization-activated K+-selective ion channels, with a
      selectivity sequence for monovalent cations of K+ > Rb+ [almost equal to] NH4+ >>
      Na+ [almost equal to] Li+ > Cs+. Kinetic analysis of K+ channel currents yielded
      an apparent K+ equilibrium dissociation constant (Km) of [almost equal to]8.8 mM,
      which closely correlates to the major component of low-affinity K+ uptake. These
      channels did not inactivate during prolonged stimulation and would thus enable
      long-term K+ uptake driven by the plasma membrane proton-extruding pump.
      Aluminum, which is known to inhibit cation uptake at the root epidermis, blocked
      these inward-rectifying K+ channels with half-maximal current inhibition at
      [almost equal to]8 [mu]M free Al3+. Aluminum block of K+ channels at these Al3+
      concentrations correlates closely to Al3+ phytotoxicity. It is concluded that
      inward-rectifying K+ channels in root hairs can function as both a
      physiologically important mechanism for low-affinity K+ uptake and as regulators
      of membrane potential. The identification of this mechanism is a major step
      toward a detailed molecular characterization of the multiple components involved
      in K+ uptake, transport, and membrane potential control in root epidermal cells.

PMID- 12232296
TI  - Effects of NaCl on Flows of N and Mineral Ions and on NO3- Reduction Rate within
      Whole Plants of Salt-Sensitive Bean and Salt-Tolerant Cotton.
AB  - The effects of NaCl on the transport rates of cations, NO3-, and reduced N
      compounds between roots and shoot and on NO3- assimilation rate were examined on
      plants of two species differing in their sensitivity to salinity, bean (Phaseolus
      vulgare L. cv Gabriella) and cotton (Gossypium hirsutum L. cv Akala). Biomass
      production after 20 d in response to 50 and 100 mM NaCl decreased by 48 and 59%
      in bean, but only 6 and 14% in cotton. The comparison of the flow patterns
      obtained for control and NaCl-fed plants showed that salinity induced a general
      decrease in all the fluxes involved in partitioning of N and the various ions.
      This decrease was markedly higher in bean than in cotton. Within either species,
      the different flows (uptake, xylem flux, phloem flux) of a given element were
      affected by NaCl to the same extent with minor exceptions. No specific effect of
      salinity on any of the components of N partitioning were discerned. The greater
      sensitivity of nitrate reductase activity to NaCl in bean leaves compared to
      cotton leaves seems to be due to a decreased compartmentalization of ions rather
      than to a difference in salt tolerance of the enzyme itself. Overall, our data
      show that alteration of mineral nutrition is not solely the reflection of a
      decreased growth rate, but also is a general process that impairs uptake of all
      the minerals even at mild NaCl salinity.

PMID- 12232297
TI  - Surfactant-Increased Glyphosate Uptake into Plasma Membrane Vesicles Isolated
      from Common Lambsquarters Leaves.
AB  - Plasma membrane vesicles were isolated from mature leaves of lambsquarters
      (Chenopodium album L.) to investigate whether this membrane is a barrier to
      glyphosate uptake and whether surfactants possess differential abilities to
      enhance glyphosate permeability. Amino acids representing several structural
      classes showed [delta]pH-dependent transport, indicating that the proteins
      necessary for active, proton-coupled amino acid transport were present and
      functional. Glyphosate uptake was very low compared to the acidic amino acid
      glutamate, indicating that glyphosate is not utilizing an endogenous amino acid
      carrier to enter the leaf cells and that the plasma membrane appears to be a
      significant barrier to cellular uptake. In addition, glyphosate flux was much
      lower than that measured for either bentazon or atrazine, both lipid-permeable
      herbicides that diffuse through the bilayer. Glyphosate uptake was stimulated by
      0.01% (v:v) MON 0818, the cationic surfactant used in the commercial formulation
      of this herbicide for foliar application. This concentration of surfactant did
      not disrupt the integrity of the plasma membrane vesicles, as evidenced by the
      stability of imposed pH gradients and active amino acid transport. Nonionic
      surfactants that disrupt the cuticle but that do not promote glyphosate toxicity
      in the field also increased glyphosate transport into the membrane vesicles.
      Thus, no correlation was observed between whole plant toxicity and surfactant
      aided uptake. Current data suggest that surfactant efficacy may be the result of
      charged surfactants' ability to diffuse away from the cuticle into the subtending
      apoplastic space, where they act directly on the plasma membrane to increase
      glyphosate uptake.

PMID- 12232298
TI  - Licodione Synthase, a Cytochrome P450 Monooxygenase Catalyzing 2-Hydroxylation of
      5-Deoxyflavanone, in Cultured Glycyrrhiza echinata L. Cells.
AB  - Cultured Glycyrrhiza echinata L. (Leguminosae) cells produce a retrochalcone
      echinatin (4,4[prime]-dihydroxy-2-methoxychalcone) and its biosynthetic
      intermediate licodione [1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)-1,3
      propanedione, a dibenzoylmethane (keto form) or its enol tautomer ([beta]
      hydroxychalcone)], when treated with elicitor-active substances, e.g. yeast
      extract. A microsomal fraction (160,000g pellet) prepared from yeast extract
      induced suspension cultures of G. echinata catalyzed the formation of licodione
      from (2S)-liquiritigenin (7,4[prime]-dihydroxyflavanone) in the presence of NADPH
      and air. This licodione synthase activity was shown to be dependent on cytochrome
      P450 by its microsomal localization, requirement of NAD(P)H and O2 for activity,
      and inhibition by typical cytochrome P450 inhibitors. Licodione synthase activity
      transiently increased in the cells after treatment with yeast extract. When (2S)
      naringenin (5,7,4[prime]-trihydroxyflavanone) and NADPH were incubated with the
      same microsomal preparation, a polar compound, which further converted into
      apigenin (5,7,4[prime]-trihydroxyflavone) when treated with acid, was produced.
      The reaction mechanism of licodione synthase is likely to be 2-hydroxylation of
      the flavanone molecule and subsequent hemiacetal opening and is possibly the same
      as the previously suggested mechanism of flavone synthase II from soybean and,
      furthermore, closely related to isoflavone synthase from Pueraria lobata.

PMID- 12232299
TI  - Small GTP-Binding Proteins and Membrane Biogenesis in Plants.

PMID- 12232301
TI  - Disruption of Maize Kernel Growth and Development by Heat Stress (Role of
      Cytokinin/Abscisic Acid Balance).
AB  - Temperature stress during kernel development affects maize (Zea mays L.) grain
      growth and yield stability. Maize kernels (hybrid A619 x W64A) were cultured in
      vitro at 3 d after pollination and either maintained at 25[deg]C or transferred
      to 35[deg]C for 4 or 8 d, then returned to 25[deg]C until physiological maturity.
      Kernel fresh and dry matter accumulation was severely disrupted by the long-term
      heat stress (8 d at 35[deg]C) and did not recover when transferred back to
      25[deg]C, resulting in abortion of 97% of the kernels. Kernels exposed to
      35[deg]C for 4 d (short-term heat stress) exhibited a recovery in kernel growth
      and water content at about 18 d after pollination and kernel abortion was reduced
      to about 23%. During the cell division phase, abscisic acid (ABA) levels showed a
      steady decline in the control but maintained a moderate level in the heat
      stressed kernels. However, later in development heat-stressed kernels had
      significantly higher levels of ABA than the control. Cytokinin analysis confirmed
      a peak in zeatin riboside and zeatin levels in control kernels at 10 to 12d after
      pollination. In contrast, kernels subjected to 4 d of heat stress had no
      detectable levels of zeatin and the zeatin riboside peak was reduced by 70% and
      delayed until 18 d after pollination. The long-term heat-stressed kernels showed
      low to nondetectable levels of either zeatin riboside or zeatin. Regression
      analysis of ABA level against cytokinin level during the endosperm cell division
      phase revealed a highly significant negative correlation in nonstressed kernels
      but no correlation in kernels exposed to short-term or long-term heat stress.
      Application of benzyladenine to heat-stressed, growth-chamber-grown plants
      increased thermotolerance in part by reducing kernel abortion at the tip and
      middle positions on the ear. These results confirm that shift in hormone balance
      of kernels is one mechanism by which heat stress disrupts maize kernel
      development. The maintenance of high levels of cytokinins in the kernels during
      heat stress appears to be important in increasing thermotolerance and providing
      yield stability of maize.

PMID- 12232300
TI  - Purification and Characterization of an Endophytic Fungal Proteinase That Is
      Abundantly Expressed in the Infected Host Grass.
AB  - A novel Acremonium typhinum proteinase that is expressed during endophytic
      infection of the grass Poa ampla Merr. was purified from endophyte-infected leaf
      sheath tissue. It is a thiol-containing serine alkaline endoproteinase with bound
      carbohydrate. In the infected host tissue, this proteinase is an abundant protein
      localized within fungal membrane vesicles and in the plant and/or fungal cell
      walls. This proteinase was not expressed constitutively during fungus culture.
      Rather, its expression appeared to be induced by nutrient depletion. Expression
      of an antigenically similar proteinase was detected in five other endophyte
      infected Poa species. The regulated expression of the proteinase in culture and
      its abundance in infected plant tissue suggest that its expression may be
      involved in the symbiotic interaction of the plant and the fungus.

PMID- 12232302
TI  - Apoplastic Peroxidases and Lignification in Needles of Norway Spruce (Picea abies
      L.).
AB  - The objective of the present study was to investigate the correlation of soluble
      apoplastic peroxidase activity with lignification in needles of field-grown
      Norway spruce (Picea abies L.) trees. Apoplastic peroxidases (EC 1.11.1.7) were
      obtained by vacuum infiltration of needles. The lignin content of isolated cell
      walls was determined by the acetyl bromide method. Accumulation of lignin and
      seasonal variations of apoplastic peroxidase activities were studied in the first
      year of needle development. The major phase of lignification started after bud
      break and was terminated about 4 weeks later. This phase correlated with a
      transient increase in apoplastic guaiacol and coniferyl alcohol peroxidase
      activity. NADH oxidase activity, which is thought to sustain peroxidase activity
      by production of H2O2, peaked sharply after bud break and decreased during the
      lignification period. Histochemical localization of peroxidase with guaiacol
      indicated that high activities were present in lignifying cell walls. In mature
      needles, lignin was localized in walls of most needle tissues including mesophyll
      cells, and corresponded to 80 to 130 [mu]mol lignin monomers/g needle dry weight.
      Isoelectric focusing of apoplastic washing fluids and activity staining with
      guaiacol showed the presence of strongly alkaline peroxidases (isoelectric point
      [greater than or equal to] 9) in all developmental stages investigated. New
      isozymes with isoelectric points of 7.1 and 8.1 appeared during the major phase
      of lignification. These isozymes disappeared after lignification was terminated.
      A strong increase in peroxidase activity in autumn was associated with the
      appearance of acidic peroxidases (isoelectric point [less than or equal to] 3).
      These results suggest that soluble alkaline apoplastic peroxidases participate in
      lignin formation. Soluble acidic apoplastic peroxidases were apparently unrelated
      to developmentally regulated lignification in spruce needles.

PMID- 12232303
TI  - Accumulation of Vacuolar H+-Pyrophosphatase and H+-ATPase during Reformation of
      the Central Vacuole in Germinating Pumpkin Seeds.
AB  - Protein storage vacuoles were examined for the induction of H+-pyrophosphatase
      (H+-PPase), H+-ATPase, and a membrane integral protein of 23 kD after seed
      germination. Membranes of protein storage vacuoles were prepared from dry seeds
      and etiolated cotyledons of pumpkin (Cucurbita sp.). Membrane vesicles from
      etiolated cotyledons had ATP- and pyrophosphate-dependent H+-transport
      activities. H+-ATPase activity was sensitive to nitrate and bafilomycin, and H+
      PPase activity was stimulated by potassium ion and inhibited by
      dicyclohexylcarbodiimide. The activities of both enzymes increased after seed
      germination. On immunoblot analysis, the 73-kD polypeptide of H+-PPase and the
      two major subunits, 68 and 57 kD, of vacuolar H+-ATPase were detected in the
      vacuolar membranes of cotyledons, and the levels of the subunits of enzymes
      increased parallel to those of enzyme activities. Small amounts of the subunits
      of the enzymes were detected in dry cotyledons. Immunocytochemical analysis of
      the cotyledonous cells with anti-H+-PPase showed the close association of H+
      PPase to the membranes of protein storage vacuoles. In endosperms of castor bean
      (Ricinus communis), both enzymes and their subunits increased after germination.
      Furthermore, the vacuolar membranes from etiolated cotyledons of pumpkin had a
      polypeptide that cross-reacted with antibody against a 23-kD membrane protein of
      radish vacuole, VM23, but the membranes of dry cotyledons did not. The results
      from this study suggest that H+-ATPase, H+-PPase, and VM23 are expressed and
      accumulated in the membranes of protein storage vacuoles after seed germination.
      Overall, the findings indicate that the membranes of protein storage vacuoles are
      transformed into those of central vacuoles during the growth of seedlings.

PMID- 12232304
TI  - Iron Inefficiency in Maize Mutant ys1 (Zea mays L. cv Yellow-Stripe) Is Caused by
      a Defect in Uptake of Iron Phytosiderophores.
AB  - To determine the Fe inefficiency factors in the maize mutant ys1 (Zea mays L. cv
      Yellow Stripe), root exudates of Fe-inefficient ys1 and of two Fe-efficient maize
      cultivars (Alice, WF9) were collected in axenic nutrient solution cultures.
      Analysis by thin-layer chromatography and high-performance liquid chromatography
      revealed that under Fe deficiency ys1 released the phytosiderophore 2[prime]
      deoxymugineic acid (DMA) in quantities similar to those of Alice and WF9. Under
      nonaxenic conditions, DMA released by plants of all three cultivars was rapidly
      decomposed by microorganisms in the nutrient solution. Uptake experiments with
      59Fe-labeled DMA, purified from root exudates of either Fe-deficient Alice or ys1
      plants, showed up to 20 times lower uptake and translocation of 59Fe in ys1 than
      in Alice or WF9 plants. The presence of microorganisms during preculture and
      short-term uptake experiments had no significant effect on uptake and
      translocation rates of 59Fe in Alice and ys1 plants. We conclude that Fe
      inefficiency in the maize mutant ys1 is the result of a defect in the uptake
      system for Fe-phytosiderophores.

PMID- 12232305
TI  - Solubilization and Reconstitution of the Mg2+/2H+ Antiporter of the Lutoid
      Tonoplast from Hevea brasiliensis Latex.
AB  - The Mg2+/2H+ antiporter recently described on lutoid membrane (Z. Amalou, R.
      Gibrat, C. Brugidou, P. Trouslot, J.d'Auzac [1992] Plant Physiol 100: 255-260)
      was solubilized by octylglucoside and reconstituted into soybean liposomes using
      the detergent dilution method. Magnesium efflux or influx experiments were used
      to generate a H+ influx or efflux, respectively, monitored with the fluorescent
      probe 9-amino-6-chloro-2-methoxyacridine. Both experiments gave saturable H+
      fluxes as a function of internal or external Mg2+ concentrations with similar
      kinetic parameters Km and Vmax. The Km value for Mg2+ (about 2 mM) was identical
      to that previously found in lyophilized-resuspended lutoid (reference therein),
      whereas the Vmax value was 14-fold higher. Since only 10% of the initial proteins
      were recovered in proteoliposomes, and electrophoretic patterns of the two kinds
      of vesicles differed significantly, it was inferred that the increase in Vmax was
      due essentially to an enrichment of the protein antiporter in the reconstituted
      fraction, owing to a selective effect of octylglucoside at both solubilization
      and reconstitution steps. None of the various divalent cations used could
      dissipate the pH gradient of control liposomes of soybean lipids, unless the
      divalent/H+ exchanger A23187 was added, whereas a rapid dissipation of the pH
      gradient was observed with reconstituted proteoliposomes from lutoid proteins,
      with the cation selectivity sequence Zn2+ > Cd2+ > Mg2+ in the millimolar
      concentration range. The divalent ions Ca2+, Ba2+, and Mn2+ were incapable of
      generating a H+ efflux in reconstituted proteoliposomes, whereas both Mg2+/H+ and
      Ca2+/H+ exchanges were observed in lyophilized-resuspended lutoids. Therefore,
      the lutoid membrane seems to contain separate Mg2+/H+ and Ca2+/H transport
      systems, the latter being eliminated during the solubilization/reconstitution of
      lutoid membrane proteins.

PMID- 12232306
TI  - Purification and Characterization of Two Distinct NAD(P)H Dehydrogenases from
      Onion (Allium cepa L.) Root Plasma Membrane.
AB  - Highly purified plasma membrane fractions were obtained from onion (Allium cepa
      L.) roots and used as a source for purification of redox proteins. Plasma
      membranes solubilized with Triton X-100 contained two distinct polypeptides
      showing NAD(P)H-dependent dehydrogenase activities. Dehydrogenase I was purified
      by gel filtration in Sephacryl S-300 HR, ion-exchange chromatography in DEAE
      Sepharose CL-6B, and dye-ligand affinity chromatography in Blue-Sepharose CL-6B
      after biospecific elution with NADH. Dehydrogenase I consisted of a single
      polypeptide of about 27 kD and an isoelectric point of about 6. Dehydrogenase II
      was purified from the DEAE-unbound fraction by chromatography in Blue-Sepharose
      CL-6B and affinity elution with NADH. Dehydrogenase II consisted of a single
      polypeptide of about 31 kD and an isoelectric point of about 8. Purified
      dehydrogenase I oxidized both NADPH and NADH, although higher rates of electron
      transfer were obtained with NADPH. Maximal activity was achieved with NADPH as
      donor and juglone or coenzyme Q as acceptor. Dehydrogenase II was specific for
      NADH and exhibited maximal activity with ferricyanide. Optimal pH for both
      dehydrogenases was about 6. Dehydrogenase I was moderately inhibited by
      dicumarol, thenoyltrifluoroacetone, and the thiol reagent N-ethyl-maleimide. A
      strong inhibition of dehydrogenase II was obtained with dicumarol,
      thenoyltrifluoroacetone, and the thiol reagent p-hydroxymercuribenzoate.

PMID- 12232307
TI  - Plant Defense Response to Fungal Pathogens (II. G-Protein-Mediated Changes in
      Host Plasma Membrane Redox Reactions).
AB  - Elicitor preparations containing the avr5 gene products from races 4 and 2.3 of
      Cladosporium fulvum, and tomato (Lycopersicon esculentum L.) cells containing the
      resistance gene Cf5 were used to investigate the involvement of redox processes
      in the production of active oxygen species associated with the plant response to
      the fungal elicitors. Here we demonstrate that certain race-specific elicitors of
      C. fulvum induced an increase in ferricyanide reduction in enriched plasma
      membrane fractions of tomato cells. The addition of elicitors to plasma membranes
      also induced increases in NADH oxidase and NADH-dependent cytochrome c reductase
      activities, whereas ascorbate peroxidase activity was decreased. These results
      suggest that changes in the host plasma membrane redox processes, transferring
      electrons from reducing agents to oxygen, could be involved in the increased
      production of active oxygen species by the race-specific elicitors. Our results
      also show that the dephosphorylation of enzymes involved in redox reactions is
      responsible for the race-specific induced redox activity. The effects of
      guanidine nucleotide analogs and mastoparan on the activation of plasma membrane
      redox reactions support the role of GTP-binding proteins in the transduction of
      signals leading to the activation of the defense response mechanisms of tomato
      against fungal pathogens.

PMID- 12232308
TI  - Regulation of Periplasmic Carbonic Anhydrase Expression in Chlamydomonas
      reinhardtii by Acetate and pH.
AB  - The effects of mixotrophic growth with acetate and growth medium pH on expression
      of extracellular carbonic anhydrase (CA) in Chlamydomonas reinhardtii were
      evaluated. Addition of 10 mM acetate to the culture medium resulted in reduction
      of CA activity that was parallel to the reduction generated by growth of the
      algae in high external CO2 concentrations. This reduction in activity is a
      consequence of lower level of the CA protein as determined by western analysis.
      Transcript abundance of cah-1, the gene encoding the low CO2-induced CA, is also
      reduced by the addition of acetate as verified by northern analysis. Measurements
      of photosynthesis and respiration suggest that the acetate-induced reduction of
      CA expression is not a function of lowered photosynthetic capacity, but may be
      the result of increased internal CO2 concentration generated by high, acetate
      stimulated respiratory rates. Growth medium pH can also influence extracellular
      CA expression. The induction of CA activity, protein abundance, and transcript
      levels by exposure to limiting inorganic carbon (Ci) concentrations is much more
      pronounced at higher than at lower pH values. The relationship between pH
      regulation of CA expression and its role in the Ci-concentrating mechanism are
      discussed.

PMID- 12232309
TI  - Structure and Function of the Golgi Complex in Rice Cells (II. Purification and
      Characterization of Golgi Membrane-Bound Nucleoside Diphosphatase).
AB  - Inosine diphosphatase bound to Golgi membranes was studied in rice (Oryza sativa
      L. cv Nipponkai) cells. The enzyme was solubilized with Triton X-100 from
      isolated rice Golgi membranes and was highly purified employing a series of
      chromatography steps in the presence of 20% glycerol and 0.1% Triton X-100. The
      apparent molecular mass of the enzyme was estimated by gel filtration column
      chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis to
      be 200 and 55 kD, respectively. The isoelectric point of the enzyme was
      determined to be 7.5. The optimal pH for the enzyme activity was around 7 and the
      enzyme required Mg2+ for hydrolyzing activity. IDP, UDP, and GDP were effective
      substrate for the purified rice Golgi membrane-bound inosine diphosphatase,
      whereas activity with ADP, CDP, and thymidine 5[prime]-diphosphate was 10 to 20%
      of IDP. The Km values for IDP, UDP, and GDP were 0.48, 0.50, and 0.67 mM,
      respectively, and Vmax values were 1.85, 1.54, and 1.67 [mu]mol min-1 mg-1,
      respectively. These results indicate that the rice Golgi enzyme is a nucleoside
      diphosphatase that is specific for IDP, UDP, and GDP. Furthermore, this rice
      Golgi nucleoside diphosphatase stimulated the activity of glucan synthase I also
      localized in rice Golgi membranes. The results strongly support the view that
      this nucleoside diphosphatase is involved in regulation of [beta]-glucan
      synthesis in the plant Golgi complex.

PMID- 12232310
TI  - Characterization of Blue-Green Fluorescence in the Mesophyll of Sugar Beet (Beta
      vulgaris L.) Leaves Affected by Iron Deficiency.
AB  - The mesophyll of sugar beet (Beta vulgaris L.) leaves emits red (chlorophyll a)
      fluorescence and blue-green fluorescence when excited with ultraviolet light. The
      intensity of blue-green fluorescence was increased in mesophylls affected by iron
      deficiency. This increase was large and progressive. It was concomitant with a
      decrease of photosynthetic pigments per unit of leaf area. Most of the increase
      in blue-green fluorescence can be explained by the decrease of the screening of
      ultraviolet light by chlorophylls and carotenoids. In addition, chlorophylls
      selectively reabsorb blue fluorescence, which leads to a change in the form of
      the fluorescence emission spectra. This effect induces an increase of the blue-to
      green fluorescence ratio in control mesophylls that was concomitant with the
      decrease of chlorophyll per unit of leaf area. Iron deficiency induced a decrease
      of the blue-to-green fluorescence ratio that may be attributed to an accumulation
      of flavins fluorescing in the green. Time-resolved fluorescence measurements
      indicate that they are mostly riboflavin and/or flavin mononucleotide phosphate.
      Our data also indicate that the blue-green fluorescence emitted from the
      mesophyll contains fluorescence of nicotinamide nucleotides.

PMID- 12232311
TI  - Response of Cultured Maize Cells to (+)-Abscisic Acid, (-)-Abscisic Acid, and
      Their Metabolites.
AB  - The metabolism and effects of (+)-S- and (-)-R-abscisic acid (ABA) and some
      metabolites were studied in maize (Zea mays L. cv Black Mexican Sweet) suspension
      cultured cells. Time-course studies of metabolite formation were performed in
      both cells and medium via analytical high-performance liquid chromatography.
      Metabolites were isolated and identified using physical and chemical methods. At
      10 [mu]M concentration and 28[deg] C, (+)-ABA was metabolized within 24 h,
      yielding natural (-)-phaseic acid [(-)-PA] as the major product. The unnatural
      enantiomer (-)-ABA was less than 50% metabolized within 24 h and gave primarily (
      )-7[prime]-hydroxyABA [(-)-7[prime]-HOABA], together with (+)-PA and ABA glucose
      ester. The distribution of metabolites in cells and medium was different,
      reflecting different sites of metabolism and membrane permeabilities of
      conjugated and nonconjugated metabolites. The results imply that (+)-ABA was
      oxidized to (-)-PA inside the cell, whereas (-)-ABA was converted to (-)-7[prime]
      HOABA at the cell surface. Growth of maize cells was inhibited by both (+)- and (
      )-ABA, with only weak contributions from their metabolites. The concentration of
      (+)-ABA that caused a 50% inhibition of growth of maize cells was approximately 1
      [mu]M, whereas that for its metabolite (-)-PA was approximately 50 [mu]M. (-)-ABA
      was less active than (+)-ABA, with 50% growth inhibition observed at about 10
      [mu]M. (-)-7[prime]-HOABA was only weakly active, with 50% inhibition caused by
      approximately 500 [mu]M. Time-course studies of medium pH indicated that (+)-ABA
      caused a transient pH increase (+0.3 units) at 6 h after addition that was not
      observed in controls or in samples treated with (-)-PA. The effect of (-)-ABA on
      medium Ph was marginal. No racemization at C-1[prime] of (+)-ABA, (-)-ABA, or
      metabolites was observed during the studies.

PMID- 12232312
TI  - A Mutant of Arabidopsis Deficient in the Elongation of Palmitic Acid.
AB  - The overall fatty acid composition of leaf lipids in a mutant of Arabidopsis
      thaliana was characterized by an increased level of 16:0 and a concomitant
      decrease of 18-carbon fatty acids as a consequence of a single recessive nuclear
      mutation at the fab1 locus. Quantitative analysis of the fatty acid composition
      of individual lipids established that lipids synthesized by both the prokaryotic
      and eukaryotic pathways were affected by the mutation. Direct enzyme assays
      demonstrated that the mutant plants were deficient in the activity of 3-ketoacyl
      acyl carrier protein synthase II; therefore, it is inferred that fab1 may encode
      this enzyme. Labeling experiments with [14C]acetate and lipase positional
      analysis indicated that the mutation results in a small shift in the partitioning
      of lipid synthesis between the prokaryotic and eukaryotic pathways. Synthesis of
      chloroplast lipids by the prokaryotic pathway was increased with a corresponding
      reduction in the eukaryotic pathway.

PMID- 12232313
TI  - Differential Exudation of Polypeptides by Roots of Aluminum-Resistant and
      Aluminum-Sensitive Cultivars of Triticum aestivum L. in Response to Aluminum
      Stress.
AB  - Cultivars of Triticum aestivum differing in resistance to Al were grown under
      aseptic conditions in the presence and absence of Al and polypeptides present in
      root exudates were collected, concentrated, and analyzed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. Upon exposure to 100 and 200 [mu]M
      Al, root elongation in Al-sensitive cultivars was reduced by 30 and 65%,
      respectively, whereas root elongation in resistant cultivars was reduced by only
      15 and 30%. Accumulation of polypeptides in the growth medium increased with time
      for 96 to 120 h, with little additional accumulation thereafter. This pattern of
      exudation was virtually unaffected by exposure to 100 [mu]M Al in the Al
      resistant cultivars Atlas 66 and Maringa, whereas total accumulation was reduced
      in sensitive cultivars. Changes in exudation were consistent with alterations in
      root elongation. Al-induced or Al-enhanced polypeptide bands were detected in
      Atlas 66 and Maringa after 72 h of exposure to Al. Increased accumulation of 12-,
      22-, and 33-kD bands was observed at 75 [mu]M Al in Atlas 66 and 12-, 23-, and
      43.5-kD bands started to appear at 50 [mu]M Al in Maringa. In the Al-sensitive
      cultivars Roblin and Katepwa, no significant effect on polypeptide profiles was
      observed at values up to 100 [mu]M Al. When root exudates were separated by
      ultrafiltration and the Al content was measured in both high molecular mass (HMM;
      >10 kD) and ultrafiltrate (<10 kD) fractions, approximately 2 times more Al was
      detected in HMM fractions from Al-resistant cultivars than from Al-sensitive
      cultivars. Dialysis of HMM fractions against water did not release this bound
      Al;digestion with protease released between 62 and 73% of total Al, with twice as
      much released from exudates of Al-resistant than of Al-sensitive cultivars. When
      plants were grown in the presence of 0 to 200 [mu]M Al, saturation of the Al
      binding capacity of HMM exudates occurred at 50 [mu]M Al in Al-sensitive
      cultivars. Saturation was not achieved in resistant cultivars. Differences in
      exudation of total polypeptides in response to Al stress, enhanced accumulation
      of specific polypeptides, and the greater association of Al with HMM fractions
      from Al-resistant cultivars suggest that root exudate polypeptides may play a
      role in plant response to Al.

PMID- 12232314
TI  - Cryopreservation of Plant Mitochondria as a Tool for Protein Import or in
      Organello Protein Synthesis Studies.
AB  - Cryopreserved chloroplasts and thylakoids have recently been proven to be
      suitable for protein import and integration assays. The possibility of recovering
      intact plant mitochondria after storage would also facilitate a wide range of
      investigations that are currently underway on the molecular biology of these
      organelles, e.g. mitochondrial transcription, RNA editing, in organello protein
      synthesis, and protein or transfer RNA import. Therefore, we addressed the
      question whether cryopreservation of isolated plant mitochondria was also
      possible. Tobacco (Nicotiana tabacum) or broad bean (Vicia faba) mitochondria
      were quick frozen and stored in liquid nitrogen in the presence of various
      concentrations of ethylene glycol as a cryoprotectant. After thawing, up to 90%
      of the mitochondria stored in 5 to 10% ethylene glycol appeared to retain an
      intact outer membrane and normal oxidative phosphorylation activity. Their
      ultrastructural aspect, observed by electron microscopy, was similar to that of
      freshly prepared mitochondria. Furthermore, efficient in organello protein
      synthesis was carried out with mitochondria stored in the presence of 7.5%
      ethylene glycol. Finally, the precursor of the [beta] subunit of the
      mitochondrial F1-ATPase from Nicotiana plumbaginifolia was successfully
      translocated into V. faba cryopreserved mitochondria and processed. These data
      demonstrate that plant mitochondria cryopreserved under the conditions described
      here remain functional and can be used for a variety of physiological and
      biochemical studies.

PMID- 12232315
TI  - Ripening of Nectarine Fruit (Changes in the Cell Wall, Vacuole, and Membranes
      Detected Using Electrical Impedance Measurements).
AB  - Electrical impedance measurements were used to characterize changes in
      intracellular and extracellular resistance as well as changes in the condition of
      membranes during ripening of nectarines (Prunus persica [L.] Batsch cv Fantasia).
      These measurements were related to changes in fruit texture assessed by flesh
      firmness and apparent juice content. An electrical model indicated that, during
      ripening (d 1-5) of freshly harvested fruit, the resistance of the cell wall and
      vacuole declined by 60 and 26%, respectively, and the capacitance of the
      membranes decreased by 9%. Accurate modeling of the impedance data required an
      additional resistance component. This resistance, which declined by 63% during
      ripening, was thought to be associated with either the cytoplasmic or membrane
      resistance. Changes in tissue resistance measured using low frequencies of
      alternating current were closely related to flesh firmness. After storage at
      0[deg]C for 8 weeks, the nectarines developed a woolly (dry) texture during
      ripening at 20[deg]C. The main difference between these chilling-injured
      nectarines and fruit ripened immediately after harvest was the resistance of the
      cell wall, which was higher in woolly tissue (4435 [omega] after 5 d at 20[deg]C)
      than in nonwoolly tissue (2911 [omega] after 5 d at 20[deg]C). The results are
      discussed in relation to physiological changes that occur during the ripening and
      development of chilling injury in nectarine fruit.

PMID- 12232316
TI  - Differential Accumulation of Manganese-Superoxide Dismutase Transcripts in Maize
      in Response to Abscisic Acid and High Osmoticum.
AB  - The plant growth regulator abscisic acid (ABA) has multiple physiological effects
      during embryogenesis and seed formation. Although a number of genes induced by
      ABA have been characterized, the functions of the encoded proteins remain, for
      the most part, obscure. In this paper we demonstrate that members of the
      manganese-superoxide dismutase (MnSod) gene family encoding antioxidant isozymes
      of known function during development and oxidative stress respond differentially
      to ABA and high osmoticum in developing maize (Zea mays L.) embryos. Expression
      of the maize Sod3.1 does not respond to ABA or high osmoticum, whereas the steady
      state levels of the maize Sod3.2, Sod3.3, and Sod3.4 transcripts are induced by
      ABA. Total SOD-3 protein and enzymatic activity, however, remain constant.
      Additionally, we examined the requirement for ABA in the accumulation of MnSod
      transcripts in response to high osmoticum in wild-type and mutant embryos of an
      ABA-deficient line (M1A4; vp5). RNA blot analyses show that multiple Sod3
      transcripts are also found in line M1A4, and ABA increases the accumulation of
      the Sod3.2, Sod3.3, and Sod3.4 transcripts in both wild-type and vp5 mutant
      embryos. Interestingly, although accumulation of the Sod3.3 and Sod3.4
      transcripts in the vp5 mutant embryo was induced by ABA, it was not induced by
      high osmoticum. Both superoxide dismutase and ABA have been implicated in plant
      tolerance to environmental stress; results from this study demonstrate a
      connection between the action of ABA and oxidative stress during embryo
      maturation in maize.

PMID- 12232317
TI  - Formation and Stabilization of Rhizosheaths of Zea mays L. (Effect of Soil Water
      Content).
AB  - Field observations have shown that rhizosheaths of grasses formed under dry
      conditions are larger, more coherent, and more strongly bound to the roots than
      those formed in wet soils. We have quantified these effects in a model system in
      which corn (Zea mays L.) primary roots were grown through a 30-cm-deep prepared
      soil profile that consisted of a central, horizontal, "dry" (9% water content) or
      "wet" (20% water content) layer (4 cm thick) sandwiched between damp soil (15-17%
      water content). Rhizosheaths formed in dry layers were 5 times the volume of the
      subtending root. In wet layers, rhizosheaths were only 1.5 times the root volume.
      Fractions of the rhizosheath soil were removed from individual roots by three
      successive treatments; sonication, hot water, and abrasion. Sonication removed 50
      and 90% of the soil from rhizosheaths formed in dry and wet soils, respectively.
      After the heat treatment, 35% of the soil still adhered to those root portions
      where rhizosheaths had developed in dry soil, compared with 2% where sheaths had
      formed in wet soil. Root hairs were 4.5 times more abundant and were more
      distorted on portions of roots from dry layers than from wet layers. Drier soil
      enhanced adhesiveness of rhizosheath mucilages and stimulated the formation of
      root hairs; both effects stabilize the rhizosheath. Extensive and stable
      rhizosheaths may function in nutrient acquisition in dry soils.

PMID- 12232318
TI  - Transport of Ascorbic and Dehydroascorbic Acids across Protoplast and Vacuole
      Membranes Isolated from Barley (Hordeum vulgare L. cv Gerbel) Leaves.
AB  - Protoplasts, vacuoles, and chloroplasts were isolated from leaves of 8-d-old
      barley (Hordeum vulgare L. cv Gerbel) seedlings. Transport of ascorbate and
      dehydroascorbate into protoplasts and vacuoles was investigated. Contents of
      ascorbic acid, glutathione, and [alpha]-tocopherol and ascorbate peroxidase
      activity and glutathione reductase activity were analyzed in protoplasts,
      vacuoles, and chloroplasts. Uptake of ascorbate and dehydroascorbate by
      protoplasts showed saturation kinetics (Km = 90 [mu]M reduced ascorbic acid, 20
      [mu]M dyhydroascorbic acid). Effects of various membrane transport inhibitors
      suggested that transport was carrier mediated and driven by a proton
      electrochemical gradient. Translocation of ascorbate and dehydroascorbate into
      vacuoles did not show saturation kinetics. Neither was it influenced by effectors
      or by ATP but only by Mg2+, suggesting that translocation did not occur by
      carrier. Ascorbic acid was predominantly localized in the cytosol. Contents in
      the chloroplasts and vacuoles were low. The results are consistent with the view
      that ascorbate is synthesized in the cytosol and released to chloroplasts,
      apoplast, and vacuole following a concentration gradient. Translocation from the
      apoplast into the cytosol is against a steep gradient and appears to control the
      concentration of ascorbic acid in the apoplast. In its function as an
      antioxidant, ascorbate in the apoplast may be oxidized to dehydroascorbate, which
      can be efficiently transported back into the cytosol for regeneration to
      ascorbate.

PMID- 12232319
TI  - The Effects of Heavy Metals and Root Immersion on Isoflavonoid Metabolism in
      Alfalfa (Medicago sativa L.).
AB  - Modest increases in the concentration of medicarpin, 6-fold in leaves and 4-fold
      in roots, were observed in alfalfa (Medicago sativa L.) seedlings treated with 1
      mM metal salts for 72 h. However, medicarpin-3-O-glucoside-6"-O-malonate (MGM)
      and formononetin-7-O-glucoside-6"-O-malonate (FGM) levels were up to 50-fold
      lower in metal-treated compared to control roots. Approximately 10% of the
      "missing" conjugates could be accounted for in the root treatment solution, where
      FGM and MGM transiently accumulated prior to their hydrolysis. Time-course
      studies revealed that total isoflavonoid content (roots plus solution) increased
      slightly after CuCl2 treatment, whereas the levels of FGM and MGM increased
      rapidly in alfalfa roots immersed in water. This increase was reduced by
      aeration. The phenylalanine ammonia-lyase inhibitor L-[alpha]-aminooxy-[beta]
      phenylpropionic acid was used to show that immersion of the roots reduced
      conjugate rates of degradation, which explains their accumulation. In contrast,
      conjugate rates of degradation were elevated in CuCl2-treated roots, with 50% of
      the increase being due to hydrolysis. Up to 90% of formononetin and medicarpin
      produced in response to CuCl2 treatment arose via conjugate hydrolysis. Our
      results demonstrate that both immersion/anaerobiosis and abiotic elicitation
      modify isoflavonoid metabolism in alfalfa, and that metal-stimulated accumulation
      of phytoalexins may arise through the release from preformed stores rather than
      de novo synthesis.

PMID- 12232320
TI  - Overproduction in Escherichia coli and Characterization of a Soybean Ferric
      Leghemoglobin Reductase.
AB  - We previously cloned and sequenced a cDNA encoding soybean ferric leghemoglobin
      reductase (FLbR), an enzyme postulated to play an important role in maintaining
      leghemoglobin in a functional ferrous state in nitrogen-fixing root nodules. This
      cDNA was sub-cloned into an expression plasmid, pTrcHis C, and overexpressed in
      Escherichia coli. The recombinant FLbR protein, which was purified by two steps
      of column chromatography, was catalytically active and fully functional. The
      recombinant FLbR cross-reacted with antisera raised against native FLbR purified
      from soybean root nodules. The recombinant FLbR, the native FLbR purified from
      soybean (Glycine max L.) root nodules, and dihydrolipoamide dehydrogenases from
      pig heart and yeast had similar but not identical ultraviolet-visible absorption
      and fluorescence spectra, cofactor binding, and kinetic properties. FLbR shared
      common structural features in the active site and prosthetic group binding sites
      with other pyridine nucleotide-disulfide oxidoreductases such as dihydrolipoamide
      dehydrogenases, but displayed different microenvironments for the prosthetic
      groups.

PMID- 12232321
TI  - Poplar Bark Storage Protein and a Related Wound-Induced Gene Are Differentially
      Induced by Nitrogen.
AB  - Poplars (Populus deltoides Bartr. ex Marsh) accumulate a 32-kD bark storage
      protein (BSP) in phloem parenchyma and xylem ray cells during autumn and winter.
      Accumulation of poplar BSP is associated with short-day (SD) photoperiods. Poplar
      BSP shares sequence similarity with the product of the wound-inducible poplar
      gene win4. The influence of nitrogen availability and photoperiod on the levels
      of BSP, BSP mRNA, and win4 mRNA was investigated. In long-day (LD) plants BSP,
      BSP mRNA, and win4 mRNA levels were correlated with the amount of NH4NO3 provided
      to the plant. BSP mRNA and BSP were detected only in bark, whereas win4 mRNA was
      detected only in leaves. In LD plants treated with NH4NO3, BSP mRNA levels were
      significantly greater than those of win4. In nitrogen-deficient plants exposed to
      SD conditions, the accumulation of BSP mRNA and BSP was delayed for 2 weeks. This
      delay was eliminated by further SD exposure, and after 6 weeks of SD treatment
      similar levels of BSP and BSP mRNA were detected in the bark of SD plants
      regardless of the level of NH4NO3 treatment. win4 mRNA levels declined to
      undetectable levels in young leaves of SD plants but increased in mature leaves.
      These results indicate that BSP accumulation in both LD and SD plants is
      influenced by nitrogen availability. Although both BSP and win4 appear to be
      involved in nitrogen storage, our data suggest that BSP is probably the primary
      protein involved in both seasonal and short-term nitrogen storage in poplar.
      These results also suggest that nitrogen cycling and storage in poplar could
      involve a two-component system. In this system the win4 gene product may modulate
      accumulation and mobilization of leaf nitrogen, whereas BSP is involved in
      seasonal and short-term nitrogen storage during periods of excess nitrogen
      availability.

PMID- 12232322
TI  - Regulation of Glutamate Dehydrogenase and Glutamine Synthetase in Avocado Fruit
      during Development and Ripening.
AB  - The activity, protein, and isoenzymic profiles of glutamate de-hydrogenase (GDH)
      and glutamine synthetase (GS) were studied during development and ripening of
      avocado (Percea americana Mill. cv Hass) fruit. During fruit development, the
      activity and protein content of both GDH and GS remained relatively constant. In
      contrast, considerable changes in these enzymes were observed during ripening of
      avocado fruit. The specific activity of GDH increased about 4-fold, coincident
      with a similar increase in GDH protein content and mRNA levels. On the other
      hand, GS specific activity showed a decline at the end of the ripening process.
      On the isoenzymic profile of GDH, changes in the prevalence of the seven
      isoenzymes were found, with a predominance of the more cathodal isoenzymes in the
      unripe and of the most anodal isoenzymes in the ripe fruit. Two-dimensional
      electrophoresis revealed that avocado fruit GDH consists of two subunits whose
      association gives rise to seven isoenzymes. The results support the view that the
      predominance of the more anodal isoenzymes in the overripe fruit was due to the
      accumulation of the [alpha]-polypeptide.

PMID- 12232323
TI  - Purification and Characterization of a Potato Tuber Acid Phosphatase Having
      Significant Phosphotyrosine Phosphatase Activity.
AB  - The major acid phosphatase (APase) from potato (Solanum tuberosom L. cv Chiefton)
      tubers has been purified 2289-fold to near homogeneity and a final O-phospho-L
      tyrosine (P-Tyr) hydrolyzing specific activity of 1917 [mu]mol Pi produced min-1
      mg-1 of protein. Nondenaturing polyacrylamide gel electrophoresis of the final
      preparation resolved a single protein-staining band that co-migrated with APase
      activity. Following sodium dodecyl sulfate polyacrylamide gel electrophoresis,
      glycosylated polypeptides of 57 and 55 kD were observed. The two polypeptides are
      immunologically closely related, since both proteins cross-reacted on immunoblots
      probed with rabbit anti-(Brassica nigra APase) immunoglobulin G. Immunoblotting
      studies revealed that the 55-kD subunit did not arise via proteolytic cleavage of
      the 57-kD subunit after tissue extraction. The native molecular mass was
      approximately 100 kD, suggesting that the holoenzyme could exist as either a
      homodimer or a heterodimer. The enzyme displayed a pH optimum of 5.8, was
      activated 40% by 4 mM Mg2+, and was potently inhibited by molybdate, vanadate,
      and ZnCl2. The final preparation displayed the highest activity and specificity
      constant with P-Tyr, but also dephosphorylated other phosphomonoesters including
      p-nitrophenylphosphate, O-phospho-L-serine, phosphoenolpyruvate, PPi, and ATP.
      Antibodies to P-Tyr were used to demonstrate that several endogenous
      phosphotyrosylated tuber polypeptides could serve as in vitro substrates for the
      purified APase. Although the precise physiological significance of the potato
      APase's substantial in vitro activity with P-Tyr remains obscure, the possibility
      that this APase may function to dephosphorylate certain protein-located P-Tyr
      residues in vivo is suggested.

PMID- 12232324
TI  - Increased Activity of [gamma]-Glutamylcysteine Synthetase in Tomato Cells
      Selected for Cadmium Tolerance.
AB  - Two cell lines of tomato (Lycopersicon esculentum Mill cv VFNT-Cherry) were
      systematically compared for their capacity to tolerate cadmium. Unselected CdS
      cells died in the presence of 0.3 mM CdCl2. CdR6-0 cells, which were selected
      from CdS, survived and grew in medium supplemented with 0.3 mM CdCl2. Growth of
      CdR6-0 cells under this condition was accompanied by synthesis of cadmium-binding
      phytochelatins and maintenance of cellular glutathione (GSH) levels. CdR6-0 cells
      also exhibited increased tolerance to buthionine sulfoximine, in both the
      presence and absence of 0.1 mM CdCl2. The specific activity of [gamma]
      glutamylcysteine synthetase (EC 6.3.2.2) was approximately 2-fold higher in CdR6
      0 cells than in CdS cells, whereas there was no difference between cell lines in
      specific activity of GSH synthetase (EC 6.3.2.3). Increased activity of the first
      enzyme of GSH biosynthesis in CdR6-0 cells, presumably a result of selection for
      increased cadmium tolerance, provides an enhanced capacity to synthesize GSH and
      to maintain the production of phytochelatins in response to cadmium. This
      adaptation may contribute to the enhanced cadmium tolerance of CdR6-0 cells.

PMID- 12232326
TI  - Acclimation of Soybean Nodules to Changes in Temperature.
AB  - This study examines how O2 status, respiration rate, and nitrogenase activity of
      soybean (Glycine max) nodules acclimate to short-term (<30 min) temperature
      change from 20 to 15[deg]C or from 20 to 25[deg]C. Acclimation responses were
      compared between nodules on uninhibited plants and nodules that were severely O2
      limited by exposure to Ar:O2. In uninhibited nodules the decrease in temperature
      caused a rapid inhibition of nitrogenase activity followed by partial recovery,
      whereas in Ar:O2-inhibited nodules the temperature decrease caused a minor
      stimulation followed by a gradual decline in nitrogenase activity. In contrast,
      the temperature increase caused a gradual increase in nitrogenase activity in
      uninhibited nodules, and an initial inhibition followed by a rapid rise in Ar:O2
      inhibited nodules. In both uninhibited and Ar:O2-inhibited nodules, temperature
      had only minor effects on the degree to which nitrogenase activity was limited by
      O2 supply, but nodule permeability to O2 diffusion was greater at 25[deg]C, and
      less at 15[deg]C, than that measured at 20[deg]C. On the basis of these data, we
      propose that temperature change alters the nodule's respiratory demand and that
      the observed changes in nodule permeability occur to maintain control over the
      infected cell O2 concentration as the O2 demand increases at high temperature or
      decreases at low temperature.

PMID- 12232325
TI  - Localization of Membrane Proteins in the Cyanobacterium Synechococcus sp. PCC7942
      (Radial Asymmetry in the Photosynthetic Complexes).
AB  - Localization of membrane proteins in the cyanobacterium Synechococcus sp. PCC7942
      was determined by transmission electron microscopy utilizing immunocytochemistry
      with cells prepared by freeze-substitution. This preparation procedure maintained
      cellular morphology and permitted detection of cellular antigens with high
      sensitivity and low background. Synechococcus sp. PCC7942 is a unicellular
      cyanobacterium with thylakoids organized in concentric layers toward the
      periphery of the cell. Cytochrome oxidase was localized almost entirely in the
      cytoplasmic membrane, whereas a carotenoprotein (P35) was shown to be a cell wall
      component. The major photosystem II (PSII) proteins (D1, D2 CP43, and CP47) were
      localized throughout the thylakoids. Proteins of the Cyt b6/f complex were found
      to have a similar distribution. Thylakoid luminal proteins, such as the Mn
      stabilizing protein, were located primarily in the thylakoid, but a small,
      reproducible fraction was found in the outer compartment. The photosystem I (PSI)
      reaction center proteins and the ATP synthase proteins were found associated
      mostly with the outermost thylakoid and with the cytoplasmic membrane. These
      results indicated that the photosynthetic apparatus is not evenly distributed
      throughout the thylakoids. Rather, there is a radial asymmetry such that much of
      the PSI and the ATPase synthase is located in the outermost thylakoid. The
      relationship of this structure to the photosynthetic mechanism is discussed. It
      is suggested that the photosystems are separated because of kinetic differences
      between PSII and PSI, as hypothesized by H.-W. Trissl and C. Wilhelm (Trends
      Biochem Sci [1993] 18:415-419).

PMID- 12232327
TI  - Biosynthesis of p-Hydroxybenzoate from p-Coumarate and p-Coumaroyl-Coenzyme A in
      Cell-Free Extracts of Lithospermum erythrorhizon Cell Cultures.
AB  - The enzymatic formation of p-hydroxybenzoate from p-coumarate in cell-free
      extracts of cell cultures of Lithospermum erythrorhizon Sieb. et Zucc. was
      investigated. p-Coumaroyl-coenzyme A (p-coumaroyl-CoA) is the activated
      intermediate in this biosynthetic reaction. It is formed by an ATP-, Mg2+ -, and
      CoA-dependent 4-hydroxycinnamate:CoA ligase reaction. p-Coumaroyl-CoA is oxidized
      and cleaved to p-hydroxybenzoyl-CoA and acetyl-CoA in a thioclastic reaction in
      which NAD is an essential cofactor. These CoA esters are rapidly hydrolyzed to
      acetate and p-hydroxybenzoate, probably by thioesterases. The enzymes involved in
      the formation of p-hydroxybenzoate are soluble. p-Hydroxybenzalde-hyde is not an
      intermediate in this conversion, and S-denosylmethionine and uridine-5[prime]
      diphosphoglucose do not enhance formation of p-hydroxybenzoate in our system.

PMID- 12232328
TI  - Gas Exchange and Carbon Partitioning in the Leaves of Celery (Apium graveolens
      L.) at Various Levels of Root Zone Salinity.
AB  - Both mannitol and sucrose (Suc) are primary photosynthetic products in celery
      (Apium graveolens L.). In other biological systems mannitol has been shown to
      serve as a compatible solute or osmoprotectant involved in stress tolerance.
      Although mannitol, like Suc, is translocated and serves as a reserve carbohydrate
      in celery, its role in stress tolerance has yet to be resolved. Mature celery
      plants exposed to low (25 mM NaCl), intermediate (100 mM NaCl), and high (300 mM
      NaCl) salinities displayed substantial salt tolerance. Shoot fresh weight was
      increased at low NaCl concentrations when compared with controls, and growth
      continued, although at slower rates, even after prolonged exposure to high
      salinities. Gas-exchange analyses showed that low NaCl levels had little or no
      effect on photosynthetic carbon assimilation (A), but at intermediate levels
      decreases in stomatal conductance limited A, and at the highest NaCl levels
      carboxylation capacity (as measured by analyses of the CO2 assimilation response
      to changing internal CO2 partial pressures) and electron transport (as indicated
      by fluorescence measurements) were the apparent prevailing limits to A.
      Increasing salinities up to 300 mM, however, increased mannitol accumulation and
      decreased Suc and starch pools in leaf tissues, e.g. the ratio of mannitol to Suc
      increased almost 10-fold. These changes were due in part to shifts in
      photosynthetic carbon partitioning (as measured by 14C labeling) from Suc into
      mannitol. Salt treatments increased the activity of mannose-6-phosphate reductase
      (M6PR), a key enzyme in mannitol biosynthesis, 6-fold in young leaves and 2-fold
      in fully expanded, mature leaves, but increases in M6PR protein were not apparent
      in the older leaves. Mannitol biosynthetic capacity (as measured by labeling
      rates) was maintained despite salt treatment, and relative partitioning into
      mannitol consequently increased despite decreased photosynthetic capacity. The
      results support a suggested role for mannitol accumulation in adaptation to and
      tolerance of salinity stress.

PMID- 12232329
TI  - Identification of Peroxisome Membrane Proteins (PMPs) in Sunflower (Helianthus
      annuus L.) Cotyledons and Influence of Light on the PMP Developmental Pattern.
AB  - Boundary membranes were recovered from glyoxysomes, transition peroxisomes, and
      leaf-type peroxisomes purified from cotyledons of sunflower (Helianthus annuus
      L.) at three stages of postgerminative growth. After membranes were washed in 100
      mM Na2CO3 (pH 11.5), integral peroxisome membrane proteins (PMPs) were
      solubilized in buffered aminocaproic acid/dodecyl maltoside (0.63 M/1.5%) and
      analyzed by nondenaturing and sodium dodecyl sulfate (SDS)-polyacrylamide gel
      electrophoresis. Six prominent nondenatured PMP complexes and 10 prominent SDS
      denatured polypeptides were identified in the membranes of the three types of
      peroxisomes. A nondenatured complex of approximately 140 kD, composed mainly of
      24.5-kD polypeptides, decreased temporally, independently of seedling exposure to
      white, blue, or red light; only far-red light seemed to prevent its decrease. PMP
      complexes of approximately 120 and 70 kD, in contrast, were present at all stages
      and changed in polypeptide content. It remains to be determined whether these
      data reflect changes within in vivo complexes or within complexes formed
      following/during detergent solubilization. Conversion of glyoxysomes to leaf-type
      peroxisomes in white or red light after a 2-d dark period was accompanied by the
      appearance of three SDS-denatured PMPs: 27.5, 28, and 47 kD. The former two
      became part of the PMP120 and 70 complexes, as well as part of a new PMP130
      complex that also possessed the PMP47. Growth of seedlings in blue or far-red
      light did not promote the appearance of PMPs 27.5 or 28. Blue light promoted the
      appearance of PMP47, and far-red light seemed to prevent its appearance.
      Chlorophyll likely is not the photoreceptor involved in accumulation of PMPs
      because the PMP composition is distinctly different in seedlings irradiated with
      red or blue light of comparable fluence rates. Several lines of evidence indicate
      that the synthesis and acquisition of membrane and all matrix proteins are not
      coupled. The data provide evidence for a change in PMP composition when sunflower
      or any other oilseed glyoxysomes are converted to leaf-type peroxisomes and
      suggest that the change is regulated by both photobiological and temporal
      mechanisms.

PMID- 12232330
TI  - Depolarization-Activated K+ Channel in Chara Droplets.
AB  - A novel potassium channel was characterized in the droplet membrane of Chara
      gymnophylla. This channel has a conductance of about 90 pS (in symmetrical 0.15 M
      KCl), which is lower compared to the 170-pS K+ channel predominant in this
      preparation. In contrast to the large conductance K+ channel, the novel channel
      opened with a delay at depolarization and closed at hyperpolarization and did not
      require cytosolic Ca2+ for its opening. It also showed comparatively weak
      selectivity for K+ over other monovalent cations, although its cation to anion
      selectivity was high. Externally or internally applied Cs+ blocked the channel in
      a voltage-dependent manner, similarly to the 170-pS channel. The sensitivity of
      the 90-pS channel to external tetraethylammonium chloride (half-blocking
      concentration approximately 1.5 mM) was 20-fold higher compared to the large
      conductance channel. With respect to its voltage-gating kinetics, the 90-pS
      channel was identified as a "slow delayed rectifier."

PMID- 12232331
TI  - Herbicidal Activity of an Isopropylmalate Dehydrogenase Inhibitor.
AB  - Isopropylmalate dehydrogenase (IPMDH) is the third enzyme specific to leucine
      biosynthesis. It catalyzes the oxidative decarboxylation of 3-isopropylmalate (3
      IPM) to 2-ketoisocaproic acid. The partially purified enzyme from pea (Pisum
      sativum L.) shows a broad pH optimum of 7.8 to 9.1 and has Km values for 3-IPM
      and NAD of 18 and 40 [mu]M, respectively. O-Isobutenyl oxalylhydroxamate (O
      IbOHA) has been discovered to be an excellent inhibitor of the pea IPMDH, with an
      apparent inhibitor constant of 5 nM. As an herbicide, O-IbOHA showed only
      moderate activity on a variety of broadleaf and grass species. We characterized
      the herbicidal activity of O-IbOHA on corn (Zea mays L.), a sensitive species;
      giant foxtail (Setaria faberi) and morning glory (Ipomoea purpurea [L.] Roth),
      moderately tolerant species; and soybean [Glycine max L. Merr.), a tolerant
      species. Differences in tolerance among the species were not due to differences
      in the sensitivity of IPMDH. Studies with [14C]O-IbOHA suggested that uptake and
      translocation were not major limitations for herbicidal activity, nor were they
      determinants of tolerance. Moreover, metabolism could not account for the
      difference in tolerance of corn, foxtail, and morning glory, although it might
      account for the tolerance of soybean. Herbicidal activity on all four species was
      correlated with the accumulation of 3-IPM in the plants.

PMID- 12232332
TI  - Response of Fructan to Water Deficit in Growing Leaves of Tall Fescue.
AB  - Changes in dry matter and water-soluble carbohydrate components, especially
      fructan, were examined in the basal 25 mm of expanding leaf blades of tall fescue
      (Festuca arundinacea Schreb.) to assess their roles in plant response to water
      deficit. Water was withheld from vegetative plants grown in soil in controlled
      environment chambers. As stress progressed, leaf elongation rate decreased sooner
      in the light period than it did in the dark period. The decrease in growth rate
      in the dark period was associated with a decrease in local relative elongation
      rates and a shortening of the elongation zone from about 25 mm (control) to 15
      mm. Dry matter content of the leaf base increased 23% during stress, due mainly
      to increased water-soluble carbohydrate near the ligule and to increased water
      soluble, carbohydrate-free dry matter at distal positions. Sucrose content
      increased 258% in the leaf base, but especially (over 4-fold) within 10 mm of the
      ligule. Hexose content increased 187% in the leaf base. Content of total fructan
      decreased to 69% of control, mostly in regions farther from the ligule. Fructan
      hydrolysis could account for the hexose accumulated. Stress caused the osmotic
      potential to decrease throughout the leaf base, but more toward the ligule. With
      stress there was 70% less direct contribution of low-degree-of-polymerization
      fructan to osmotic potential in the leaf base, but that for sucrose and hexose
      increased 96 and 67%, respectively. Thus, fructan metabolism is involved but
      fructan itself contributes only indirectly to osmotic adjustment.

PMID- 12232333
TI  - Metabolism and Synthesis of Indole-3-Acetic Acid (IAA) in Zea mays (Levels of IAA
      during Kernel Development and the Use of in Vitro Endosperm Systems for Studying
      IAA Biosynthesis).
AB  - Kernels of Zea mays on an intact plant accumulate indole-3-acetic acid (IAA) at
      the rate of 190 ng g-1 fresh weight h-1. Of the IAA synthesized, 97% is in the
      esterified form and less than 3% remains as the free acid. The site of
      biosynthesis of the IAA, whether synthesized in the leaf and transported to the
      kernel, or in the kernel and remaining in the kernel, has not been established.
      In an attempt to determine the locus of synthesis, we grew isolated kernels on
      agar media not containing tryptophan or other possible aromatic precursors of IAA
      and observed IAA synthesis of 99 ng g-1 fresh weight h-1, approximately 52% of
      the in situ rate. Thus, the kernel contains all of the enzymes required for de
      novo aromatic biosynthesis of IAA and its ester conjugates. Furthermore,
      endosperm cells in suspension culture, grown on hormone-free media and in the
      absence of aromatic precursors, are able to synthesize IAA at a rate of 9.2 ng g
      1 fresh weight h-1, or 4.8% of the in situ rate. This finding establishes that
      all of the enzymes of IAA biosynthesis occur in the endosperm and that the
      endosperm is a site of IAA biosynthesis. Isolated endosperm, prepared from
      developing kernels, synthesized IAA from labeled anthranilate at a rate of 8.6 ng
      g-1 fresh weight h-1, or 4.5% of the in situ rate. Frozen endosperm preparations
      maintained the ability to synthesize labeled IAA from labeled anthranilate. The
      identity of the synthesized IAA was established by mass spectral analysis. We
      suggest that endosperm preparations of Z. mays are suitable for study of the
      mechanism(s) of IAA biosynthesis because they (a) have high rates of synthesis;
      (b) show stability to freezing, enabling enzyme storage; (c) provide a system
      with a known rate of in situ synthesis; and (d) are available in large amounts
      for use as an enzyme source.

PMID- 12232334
TI  - Counteractive Effects of ABA and GA3 on Extracellular and Intracellular pH and
      Malate in Barley Aleurone.
AB  - Barley (Hordeum vulgare L.) aleurone layers are known to constitutively acidify
      their surroundings, primarily by L-malic acid release (J. Mikola, M. Virtanen
      [1980] Plant Physiol 66: S-142). Here we demonstrate the antagonistic effects of
      the plant hormones gibberellic acid (GA3) and abscisic acid (ABA) on the
      regulation of extracellular pH (pHe) of barley aleurone layers. We observed a
      strong correlation between ABA-induced enhancement of extracellular acidification
      and an ABA-induced increase in L-malic acid release. In addition, ABA caused an
      increase in intracellular L-malate level. GA3 caused a slight decrease in
      intracellular L-malate level and was able to inhibit the ABA-induced increase in
      L-malate intracellular concentration and release. In addition, this ABA-induced L
      malate release could be completely inhibited by GA3. The ABA-induced release of L
      malic acid could not account for the total ABA-induced pHe decrease, suggesting
      the existence of an additional mechanism involved in the regulation of pHe. It
      has been reported that ABA induces an intracellular pH (pHi) increase, possibly
      due to the activation of plasma membrane proton pumps (R. Van der Veen, S.
      Heimovaara-Dijkstra, M. Wang [1992] Plant Physiol 100: 699-705). A pHi increase,
      such as that caused by ABA, might be correlated with the intracellular L-malate
      increase as suggested by the pH stat model of D.D. Davies ([1986] Physiol Plant
      67: 702-706). We studied if the effects of GA3 on L-malate concentration were
      correlated with changes in pHi and found that GA3 caused a pHi decrease and that
      GA3 and ABA could interfere in the regulation of pHi. In addition, we were able
      to mimic the effect of both hormones on L-malate release by bringing about
      artifical pHi changes with the weak acid 5,5-dimethyl-2,4-oxazolidinedione and
      the weak base methylamine. The physiological meaning of the effects of GA3 and
      ABA on the regulation of both pHe and pHi during grain germination are discussed.

PMID- 12232335
TI  - Genetically Programmed Chloroplast Dedifferentiation as a Consequence of Plastome
      Genome Incompatibility in Oenothera.
AB  - Comparision of chloroplast from plants with one of four plastome types (I, II,
      III, IV) in the nuclear background of Oenothera elata strain Johansen addressed
      the effects of plastome-genome incompatibility with respect to leaf pigmentation,
      plastid ultrastructure, chlorophyll a/chlorophyll b ratio, and photosynthetic
      electron transport. Previous observations of plastomes I, II, and IV in this
      nuclear background have revealed no indications of incompatibility, but the
      studies reported here demonstrate that chloroplasts of plastome IV have subtle
      alterations in their photosynthetic abilities, in particular, deficiencies in
      photosystem II. The well-characterized "hybrid bleaching" of plants with the AA
      genotype and plastome III involves leaves that become bleached in the center
      while remaining green at the tips, edges, and veins. Electron transport assays
      performed on fractionated bleached and green tissue from the same plants show
      photosynthetic defects in both the green and bleached regions, although defects
      in the latter are more severe. Ultrastructural studies show that chloroplasts in
      the bleached areas enlarge, thylakoid membranes become swollen and vesiculated,
      and production of new thylakoids is blocked, with chloroplasts appearing to
      undergo a programmed senescence. A time course revealed that the senescence is
      actually a reversible dedifferentiation. Alterations in the composition of medium
      to which AA/III seedlings were transferred showed that the presence of auxin can
      prevent the development of the typical incompatibility response, with leaf tissue
      remaining green rather than bleaching. It is proposed that differences in
      concentrations of plant growth regulators may be responsible for the persistence
      of normal chloroplasts near the vascular tissue and leaf blade edges and that
      seasonal fluctuations in auxin levels could explain the periodic bleaching that
      occurs in older plants.

PMID- 12232336
TI  - Anion Selectivity of Slow Anion Channels in the Plasma Membrane of Guard Cells
      (Large Nitrate Permeability).
AB  - Closing of stomatal pores in the leaf epidermis of higher plants is mediated by
      long-term release of potassium and the anions chloride and malate from guard
      cells and by parallel metabolism of malate. Previous studies have shown that
      slowly activating anion channels in the plasma membrane of guard cells can
      provide a major pathway for anion efflux while also controlling K+ efflux during
      stomatal closing: Anion efflux produces depolarization of the guard cell plasma
      membrane that drives K+ efflux required for stomatal closing. The patch-clamp
      technique was applied to Vicia faba guard cells to determine the permeability of
      physiologically significant anions and halides through slow anion channels to
      assess the contribution of these anion channels to anion efflux during stomatal
      closing. Permeability ratio measurements showed that all tested anions were
      permeable with the selectivity sequence relative to Cl- of NO3- > Br- > F- ~ Cl-
      ~ I- > malate. Large malate concentrations in the cytosol (150 mM) produced a
      slow down-regulation of slow anion channel currents. Single anion channel
      currents were recorded that correlated with whole-cell anion currents. Single
      slow anion channels confirmed the large permeability ratio for nitrate over
      chloride ions. Furthermore, single-channel studies support previous indications
      of multiple conductance states of slow anion channels, suggesting cooperativity
      among anion channels. Anion conductances showed that slow anion channels can
      mediate physiological rates of Cl- and initial malate efflux required for
      mediation of stomatal closure. The large NO3- permeability as well as the
      significant permeabilities of all anions tested indicates that slow anion
      channels do not discriminate strongly among anions. Furthermore, these data
      suggest that slow anion channels can provide an efficient pathway for efflux of
      physiologically important anions from guard cells and possibly also from other
      higher plant cells that express slow anion channels.

PMID- 12232337
TI  - Efficiency of Nitrogen Utilization in C3 and C4 Cereals.

PMID- 12232338
TI  - Regulation of Light Harvesting in Green Plants (Indication by Nonphotochemical
      Quenching of Chlorophyll Fluorescence).

PMID- 12232339
TI  - High-Oleate Oilseeds Fail to Develop at Low Temperature.
AB  - The fad2 mutants of Arabidopsis thaliana are deficient in activity of the
      endoplasmic reticulum oleate desaturase that is the main enzyme responsible for
      polyunsaturated lipid synthesis in developing seeds of oil crops. A comparison of
      wild-type and fad2 seeds developing on heterozygous (FAD2/-) plants was used as a
      model for genetically engineered high-oleate oilseeds of species such as soybean
      and canola. When fad2 seeds developed at normal temperatures (22[deg]C), they
      showed high viability compared to wild-type seeds. When a portion of seed
      development took place at 6[deg]C, germination of the wild-type siblings remained
      high but germination of fad2 segregants declined considerably. This was true even
      when exposure to low temperature was limited to the final stages of seed filling
      and maturation. Compared to wild-type seeds, fully viable fad2 seeds produced at
      22[deg]C had reduced lipid contents and were slower to germinate at 10 and
      6[deg]C. Taken together, these results indicate that for some oilseed species at
      least, molecular genetic manipulation of oleate levels in the oil may result in
      plant lines with unacceptable performance in the field.

PMID- 12232340
TI  - Reduction in Pectin Methylesterase Activity Modifies Tissue Integrity and Cation
      Levels in Ripening Tomato (Lycopersicon esculentum Mill.) Fruits.
AB  - Pectin methylesterase (PME, EC 3.1.1.11) is an ubiquitous enzyme in the plant
      kingdom; however, its role in plant growth and development is not yet understood.
      Using transgenic tomato (Lycopersicon esculentum Mill.) fruits that show more
      than 10-fold reduction in PME activity because of expression of an antisense PME
      gene, we have investigated the role of PME in tomato fruit ripening. Our results
      show that reduced PME activity causes an almost complete loss of tissue integrity
      during fruit senescence but shows little effect on fruit firmness during
      ripening. Low PME activity in the transgenic fruit pericarp modified both
      accumulation and partitioning of cations between soluble and bound forms and
      selectively impaired accumulation of Mg2+ over other major cations. Decreased PME
      activity was associated with a 30 to 70% decrease in bound Ca2+ and Mg2+ in
      transgenic pericarp. Levels of soluble Ca2+ increase 10 to 60%, whereas levels of
      soluble Mg2+ and Na+ are reduced by 20 to 60% in transgenic pericarp. Changes in
      cation levels associated with lowered PME activity do not affect the rate of
      respiration or membrane integrity of fruit during ripening. Overall, these
      results suggest that PME plays a role in determining tissue integrity during
      fruit senescence, perhaps by regulating cation binding to the cell wall.

PMID- 12232341
TI  - Utilization of Amygdalin during Seedling Development of Prunus serotina.
AB  - Cotyledons of mature black cherry (Prunus serotina Ehrh.) seeds contain the
      cyanogenic diglucoside (R)-amygdalin. The levels of amygdalin, its corresponding
      monoglucoside (R)-prunasin, and the enzymes that metabolize these cyanoglycosides
      were measured during the course of seedling development. During the first 3 weeks
      following imbibition, cotyledonary amygdalin levels declined by more than 80%,
      but free hydrogen cyanide was not released to the atmosphere. Concomitantly,
      prunasin, which was not present in mature, ungerminated seeds, accumulated in the
      seedling epicotyls, hypocotyls, and cotyledons to levels approaching 4 [mu]mol
      per seedling. Whether this prunasin resulted from amygdalin hydrolysis remains
      unclear, however, because these organs also possess UDPG:mandelonitrile
      glucosyltransferase, which catalyzes de novo prunasin biosynthesis. The reduction
      in amygdalin levels was paralleled by declines in the levels of amygdalin
      hydrolase (AH), prunasin hydrolase (PH), mandelonitrile lyase (MDL), and [beta]
      cyanoalanine synthase. At all stages of seedling development, AH and PH were
      localized by immunocytochemistry within the vascular tissues. In contrast, MDL
      occurred mostly in the cotyledonary parenchyma cells but was also present in the
      vascular tissues. Soon after imbibition, AH, PH, and MDL were found within
      protein bodies but were later detected in vacuoles derived from these organelles.

PMID- 12232342
TI  - Rice Triosephosphate Isomerase Gene 5[prime] Sequence Directs [beta]
      Glucuronidase Activity in Transgenic Tobacco but Requires an Intron for
      Expression in Rice.
AB  - In rice (Oryza sativa L.), cytosolic triosephosphate isomerase (TPI) is encoded
      by a single gene. TPI catalyzes a vital step in glycolysis, and RNA blots showed
      that the tpi gene is expressed in all vegetative tissues (root, culm, and leaves)
      and in rice suspension cells. No effect of light on expression was detected, but
      submergence of rice seedlings resulted in elevated levels of TPI mRNA in roots
      and culms. The 2767-bp 5[prime] upstream sequence of the tpi gene was fused
      translationally with the [beta]-glucuronidase (gusA) gene, and the resulting
      construct, TPI-GUS, was found to express constitutive, high levels of GUS
      activity in transgenic tobacco (Nicotiana tabacum) plants. However, the same
      construct yielded no GUS activity in stably transformed rice plants, and RNA
      blots showed that no GUS mRNA could be detected even though stable integration of
      functional copies of the construct was confirmed by Southern blot and genomic
      polymerase chain reaction analyses. Transient assays using particle bombardment
      yielded high levels of GUS expression from the TPI-GUS construct in tobacco
      leaves, but essentially no expression in rice, barley, or maize leaves. When the
      first intron of the tpi gene was included in the construct (TPI-int1-GUS),
      transient GUS activity was routinely obtained in rice leaves, revealing that the
      first intron of the rice tpi gene is crucial for its expression in rice. TPI-int1
      GUS also directed transient GUS expression in maize and barley leaves, but little
      or no activity was obtained from this construct in tobacco, tomato, or soybean
      leaves. These results with the rice tpi promoter are in accordance with mounting
      evidence that differences in gene expression exist between monocots and dicots.

PMID- 12232343
TI  - Effects of the Indole-3-Acetic Acid (IAA) Transport Inhibitors N-1
      Naphthylphthalamic Acid and Morphactin on Endogenous IAA Dynamics in Relation to
      Compression Wood Formation in 1-Year-Old Pinus sylvestris (L.) Shoots.
AB  - Both N-1-naphthylphthalamic acid (NPA) and methyl-2-chloro-9-hydroxyfluorene-9
      carboxylic acid (CF) inhibit the polar transport of indole-3-acetic acid (IAA)
      and, therefore, are attractive tools for investigating IAA's role in the
      regulation of plant growth. Ringing an intact conifer shoot with lanolin
      containing NPA or CF induces the formation of compression wood above the ring.
      This induction has been attributed to a postulated accumulation of IAA above the
      application site of the IAA transport inhibitor, but the validity of this
      postulation has never been confirmed. Using gas chromatography-selected ion
      monitoring-mass spectroscopy with [13C6]IAA as an internal standard, we measured
      the levels of endogenous free and conjugated IAA in 1-year-old Pinus sylvestris
      (L.) shoots ringed with NPA or CF. The level of free IAA was dramatically
      decreased below the ring, indicating that the polar transport of endogenous IAA
      was inhibited by the treatment. However, the free IAA level above the ring, where
      compression wood was formed, was also slightly lower than in control shoots. The
      lack of IAA accumulation above the site of the IAA transport inhibitor could not
      be explained by an increase in IAA conjugation. Furthermore, the turnover of [2
      14C]IAA, measured using high-performance liquid chromatography with on-line
      radioactivity monitoring, was the same in NPA-treated and control shoots. The
      decrease in IAA level above a NPA or CF ring is attributed to these substances
      being transported acropetally and interfering with polar IAA transport along the
      shoot. It is concluded that compression wood formation above a NPA or CF ring is
      not associated with an overall increase in cambial region IAA level or increased
      IAA turnover. Instead, we suggest that acropetally transported NPA and CF induce
      compression wood formation by interacting with the NPA receptor in
      differentiating tracheids, thereby locally increasing IAA in these cells.

PMID- 12232344
TI  - Carbon-Isotope Composition of Biochemical Fractions and the Regulation of Carbon
      Balance in Leaves of the C3-Crassulacean Acid Metabolism Intermediate Clusia
      minor L. Growing in Trinidad.
AB  - Carbon-isotope ratios ([delta]13Cs) were measured for various bio-chemical
      fractions quantitatively extracted from naturally exposed and shaded leaves of
      the C3-Crassulacean acid metabolism (CAM) intermediate Clusia minor, sampled at
      dawn and dusk on days during the wet and dry seasons in Trinidad. As the activity
      of CAM increased in response to decreased availability of water and higher photon
      flux density, organic acids and soluble sugars were enriched in 13C by
      approximately 3.5 to 4%[per mille (thousand) sign] compared to plants sampled
      during the wet season. The induction of CAM was accompanied by a doubling in size
      of the reserve carbohydrate pools. Moreover, stoichiometric measurements
      indicated that degradation of both chloroplastic reserves and soluble sugars were
      necessary to supply phosphoenolpyruvate for the synthesis of organic acids at
      night. Results also suggest that two pools of soluble sugars exist in leaves of
      C. minor that perform CAM, one a vacuolar pool enriched in 13C and the second a
      transport pool depleted in 13C. Estimates of carbon-isotope discrimination
      expressed during CAM, derived from the trafficking among inorganic carbon,
      organic acids, and carbohydrate pools overnight, ranged from 0.9 to 3.1%[per
      mille (thousand) sign]. The [delta]13C of structural material did not change
      significantly between wet and dry seasons, indicating that most of the carbon
      used in growth was derived from C3 carboxylation.

PMID- 12232345
TI  - Mannitol Metabolism in Celery Stressed by Excess Macronutrients.
AB  - The effect of excess macronutrients in the root environment on mannitol and
      sucrose metabolism was investigated in celery (Apium graveolens L. var dulce
      [Mill.] Pers.). Plant growth was inhibited progressively as macronutrient
      concentration in the media, as measured by electrical conductivity (E.C.),
      increased from 1.0 to 11.9 decisiemens m-1. Plants grown for 35 d at higher E.C.
      had a lower water content but similar dry weight in their roots, leaves, and
      petioles compared to plants grown at lower E.C. Macronutrient concentrations of
      leaves, roots, and petioles were not affected by the imposed stress, indicating
      that the macronutrient stress resulted in a water-deficit stress response rather
      than a salt-specific response. Mannitol accumulated in sink tissues and was
      accompanied by a drastic decrease in activity of mannitol-1-oxidoreductase.
      Sucrose concentration and activities of sucrose-metabolizing enzymes in sink
      tissues were not affected by the macronutrient stress. Mature leaves exhibited
      increased concentrations of both mannitol and sucrose, together with increased
      activity of mannose-6-phosphate reductase and sucrose phosphate synthase, in
      response to macronutrient stress. Thus, mannitol accumulation in osmotically
      stressed celery is regulated by diminished catabolism in sink tissues and
      increased capacity for mannitol biosynthesis in source leaves.

PMID- 12232346
TI  - Ammonium Assimilation and the Role of [gamma]-Aminobutyric Acid in pH Homeostasis
      in Carrot Cell Suspensions.
AB  - In vivo 15N NMR spectroscopy was used to monitor the assimilation of ammonium by
      cell-suspension cultures of carrot (Daucus carota L. cv Chantenay). The cell
      suspensions were supplied with oxygen in the form of either pure oxygen
      ("oxygenated cells") or air ("aerated cells"). In contrast to oxygenated cells,
      in which ammonium assimilation had no effect on cytoplasmic pH, ammonium
      assimilation by aerated cells caused a decrease in cytoplasmic pH of almost 0.2
      pH unit. This led to a change in nitrogen metabolism resulting in the
      accumulation of [gamma]-aminobutyric acid. The metabolic effect of the reduced
      oxygen supply under aerated conditions could be mimicked by artificially
      decreasing the cytoplasmic pH of oxygenated cells and was abolished by increasing
      the cytoplasmic pH of aerated cells. The activity of glutamate decarboxylase
      increased as the cytoplasmic pH declined and decreased as the pH recovered. These
      findings are consistent with a role for the decarboxylation of glutamate, a
      proton-consuming reaction, in the short-term regulation of cytoplasmic pH, and
      they demonstrate that cytoplasmic pH influences the pathways of intermediary
      nitrogen metabolism.

PMID- 12232347
TI  - The Apparent Turnover of 1-Aminocyclopropane-1-Carboxylate Synthase in Tomato
      Cells Is Regulated by Protein Phosphorylation and Dephosphorylation.
AB  - In suspension-cultured cells of tomato (Lycopersicon esculentum Mill.), the
      activity of 1-aminocyclopropane-1-carboxylate synthase (ACC-S) rapidly increases
      in response to fungal elicitors. The effect of inhibitors of protein kinases and
      protein phosphatases on the regulation of ACC-S was studied. K-252a, an inhibitor
      of protein kinases, prevented induction of the enzyme by elicitors and promoted
      its apparent turnover in elicitor-stimulated cells, causing a 50% loss of
      activity within 4 to 8 min in both the presence and absence of cycloheximide.
      Calyculin A, an inhibitor of protein phosphatases, caused a rapid increase of ACC
      S in the absence of elicitors and an immediate acceleration of the rate of ACC-S
      increase in elicitor-stimulated cells. In the presence of cycloheximide there was
      no such increase, indicating that the effect depended on protein synthesis.
      Cordycepin, an inhibitor of mRNA synthesis, did not prevent the elicitor-induced
      increase in ACC-S activity but strongly reduced the K-252a-induced decay and the
      calyculin A-induced increase of its activity. In vitro, ACC-S activity was not
      affected by K-252a and calyculin A or by treatments with protein phosphatases.
      These results suggest that protein phosphorylation/dephosphorylation is involved
      in the regulation of ACC-S, not by regulating the catalytic activity itself but
      by controlling the rate of turnover of the enzyme.

PMID- 12232348
TI  - Leaf Developmental Age Controls Expression of Genes Encoding Enzymes of
      Chlorophyll and Heme Biosynthesis in Pea (Pisum sativum L.).
AB  - The effects of leaf developmental age on the expression of three nuclear gene
      families in pea (Pisum sativum L.) coding for enzymes of chlorophyll and heme
      biosynthesis have been examined. The steady-state levels of mRNAs encoding
      aminolevulinic acid (ALA) dehydratase, porphobilinogen (PBG) deaminase, and
      NADPH:protochlorophyllide reductase were measured by RNA gel blot and
      quantitative slot-blot analyses in the foliar leaves of embryos that had imbibed
      for 12 to 18 h and leaves of developing seedlings grown either in total darkness
      or under continuous white light for up to 14 d after imbibition. Both ALA
      dehydratase and PBG deaminase mRNAs were detectable in embryonic leaves, whereas
      mRNA encoding the NADPH:protochlorophyllide reductase was not observed at this
      early developmental stage. All three gene products were found to increase to
      approximately the same extent in the primary leaves of pea seedlings during the
      first 6 to 8 d after imbibition (postgermination) regardless of whether the
      plants were grown in darkness or under continuous white-light illumination. In
      the leaves of dark-grown seedlings, the highest levels of message accumulation
      were observed at approximately 8 to 10 d postgermination, and, thereafter, a
      steady decline in mRNA levels was observed. In the leaves of light-grown
      seedlings, steady-state levels of mRNA encoding the three chlorophyll
      biosynthetic enzymes were inversely correlated with leaf age, with youngest,
      rapidly expanding leaves containing the highest message levels. A corresponding
      increase in the three enzyme protein levels was also found during the early
      stages of development in the light or darkness; however, maximal accumulation of
      protein was delayed relative to peak levels of mRNA accumulation. We also found
      that although protochlorophyllide was detectable in the leaves immediately after
      imbibition, the time course of accumulation of the phototransformable form of the
      molecule coincided with NADPH:protochlorophyllide reductase expression. In
      studies in which dark-grown seedlings of various ages were subsequently
      transferred to light for 24 and 48 h, the effect of light on changes in steady
      state mRNA levels was found to be more pronounced at later developmental stages.
      These results suggest that the expression of these three genes and likely those
      genes encoding other chlorophyll biosynthetic pathway enzymes are under the
      control of a common regulatory mechanism. Furthermore, it appears that not light,
      but rather as yet unidentified endogenous factors, are the primary regulatory
      factors controlling gene expression early in leaf development.

PMID- 12232350
TI  - Cell Wall Metabolism in Ripening Fruit (VII. Biologically Active Pectin Oligomers
      in Ripening Tomato (Lycopersicon esculentum Mill.) Fruits).
AB  - A water-soluble, ethanol-insoluble extract of autolytically inactive tomato
      (Lycopersicon esculentum Mill.) pericarp tissue contains a series of galacturonic
      acid-containing (pectic) oligosaccharides that will elicit a transient increase
      in ethylene biosynthesis when applied to pericarp discs cut from mature green
      fruit. The concentration of these oligosaccharides in extracts (2.2 [mu]g/g fresh
      weight) is in excess of that required to promote ethylene synthesis. Oligomers in
      extracts of ripening fruits were partially purified by preparative high
      performance liquid chromatography, and their compositions are described. Pectins
      were extracted from cell walls prepared from mature green fruit using chelator
      and Na2CO3 solutions. These pectins are not active in eliciting ethylene
      synthesis. However, treatment of the Na2CO3-soluble, but not the chelator
      soluble, pectin with pure tomato polygalacturonase 1 generates oligomers that are
      similar to those extracted from ripening fruit (according to high-performance
      liquid chromatography analysis) and are active as elicitors. The possibility that
      pectin-derived oligomers are endogenous regulators of ripening is discussed.

PMID- 12232349
TI  - Inhibitors of Protein Phosphatases 1 and 2A Block the Sugar-Inducible Gene
      Expression in Plants.
AB  - Genes coding for two major proteins of the tuberous root of sweet potato (Ipomoea
      batatas), namely, sporamin and [beta]-amylase, are inducible in leaves and
      petioles when they are supplied with high concentrations of sucrose or other
      metabolizable sugars, such as glucose and fructose, and the accumulation of a
      large amount of starch accompanies this induction. Three inhibitors of protein
      phosphatases 1 (PP1) and 2A (PP2A), namely, okadaic acid, microcystin-LR, and
      calyculin A, strongly inhibited the sucrose-inducible accumulation of mRNAs for
      sporamin, [beta]-amylase, and the small subunit of ADP-glucose pyrophosphorylase
      in petioles. However, these inhibitors did not have any major effect on the
      steady-state levels of mRNAs for catalase and glyceraldehyde-3-phosphate
      dehydrogenase, and the sucrose-inducible increase in the level of sucrose
      synthase mRNA was enhanced by okadaic acid. Inhibitors of PP1 and PP2A also
      inhibited sucrose-inducible expression of a fusion gene, consisting of the
      promoter of the sweet potato gene for [beta]-amylase and the coding sequence for
      [beta]-glucuronidase (GUS), in leaves of transgenic tobacco (Nicotiana tabacum).
      The inhibition was not due to inhibition of uptake and cleavage of sucrose, since
      okadaic acid also inhibited induction of the fusion gene by glucose or fructose.
      Addition of okadaic acid to leaves that had been treated with sucrose for 6 h
      inhibited further increases in GUS activity. These results suggest that the
      continuous dephosphorylation of proteins is required in the transduction of
      carbohydrate metabolic signals to the transcriptional activation of at least some
      sugar-inducible genes in plant.

PMID- 12232351
TI  - Biogenesis of Thylakoid Membranes in Chlamydomonas reinhardtii y1 (A Kinetic
      Study of Initial Greening).
AB  - Initiation of thylakoid membrane assembly was examined in degreened cells of
      Chlamydomonas reinhardtii y1 cells depleted of thylakoid membranes and
      photosynthetic activity by growth in the dark for 3 to 4 d. Photoreductive
      activities of photosystem II (PSII) and photosystem I (PSI) increased with no
      apparent lag when degreened cells were exposed to light at 38[deg]C. However,
      fluorescence transients induced by actinic light, which reflect the functional
      state of PSII, changed only slightly during the first 2 h of greening. When these
      cells were treated with 3-(3,4-dichlorophenyl)-1,1-dimethyl urea (DCMU) or
      saturating light, fluorescence increased commensurate with the cellular content
      of chlorophyll. In similar experiments with greening cells of C. reinhardtii CC
      2341 (ac-u-g-2.3), a PSI-minus strain, fluorescence increased with chlorophyll
      without treatment with DCMU. These data suggested that fluorescence of initial
      PSII centers in greening y1 cells was quenched by activity of PSI. Continuous
      monitoring of fluorescence in the presence or absence of DCMU showed that
      assembly of quenched PSII centers occurred within seconds after exposure of y1
      cells to light. These results are consistent with initial assembly of PSI and
      PSII within localized domains, where their proximity allows efficient energy
      coupling.

PMID- 12232352
TI  - Modeling Carbon Export Out of Mature Peach Leaves.
AB  - The characteristics of sorbitol and sucrose export out of mature leaves in
      seedlings of peach (Prunus persica L. Batsch cv GF 305) were investigated by
      simulating carbon fluxes through the leaf. Three treatments were employed: a
      control treatment and two treatments modifying leaf export, the latter using
      either shading or girdling. Photosynthesis and 14C partitioning into sorbitol and
      sucrose were measured during carbohydrate pool buildup at the beginning of the
      photoperiod, and the export rate of sorbitol and sucrose was modeled using a
      PSPICE (Simulation Program with Integrated Circuit Emphasis) simulator. The
      simulation allowed prediction of the resulting sorbitol and sucrose contents,
      which were compared to experimental carbohydrate contents. The apparent Km for
      sorbitol and sucrose phloem loading, estimated by carbon flux modeling, was 6.6
      and 4 mol m-3, respectively. The predicted export capacity of the leaf,
      characterized by the estimated Vmax values for phloem loading of sorbitol and
      sucrose, was similar to the photosynthetic carbon flux measured under the leaf
      growth conditions. This export capacity was enhanced in plants in which all
      leaves except those studied were shaded. The mature leaf had a higher storage
      capacity for sorbitol than for sucrose in control plants, especially in the
      girdled treatment. Sucrose content appears to be tightly regulated.

PMID- 12232353
TI  - Ethylene Production during Development of Mustard (Brassica juncea) and Canola
      (Brassica napus) Seed.
AB  - An open, continuous flow system was used to investigate ethylene production
      during degreening of maturing seed of mustard (Brassica juncea cv Cutlass and cv
      Lethbridge 22A) and canola (Brassica napus cv Westar and cv Alto). Isolated
      mustard seed evolved higher amounts of ethylene than those of canola, and this
      was particularly evident both early in embryogeny and later during the
      desiccation phase of seed maturation. The silique walls produced negligible
      amounts of ethylene in both species. The concentrations of ethylene surrounding
      seed as they matured within siliques were significantly higher in mustard than in
      canola, and this interspecies difference was greatest during the seed desiccation
      phase. In mustard, a 4-fold increase in silique internal ethylene levels was
      apparent during desiccation. In comparison, only a moderate increase in silique
      derived ethylene occurred in canola.

PMID- 12232354
TI  - Root Growth Maintenance at Low Water Potentials (Increased Activity of Xyloglucan
      Endotransglycosylase and Its Possible Regulation by Abscisic Acid).
AB  - Previous work suggested that an increase in cell wall-loosening contributes to
      the maintenance of maize (Zea mays L.) primary root elongation at low water
      potentials ([psi]w). It was also shown that root elongation at low [psi]w
      requires increased levels of abscisic acid (ABA). In this study we investigated
      the effects of low [psi]w and ABA status on xyloglucan endotransglycosylase (XET)
      activity in the root elongation zone. XET is believed to contribute to wall
      loosening by reversibly cleaving xyloglucan molecules that tether cellulose
      microfibrils. The activity of XET per unit fresh weight in the apical 10 mm
      (encompassing the elongation zone) was constant at high [psi]w but increased by
      more than 2-fold at a [psi]w of -1.6 MPa. Treatment with fluridone to decrease
      ABA accumulation greatly delayed the increase in activity at low [psi]w. This
      effect was largely overcome when internal ABA levels were restored by exogenous
      application. Spatial distribution studies showed that XET activity was increased
      in the apical 6 mm at low [psi]w whether expressed per unit fresh weight, total
      soluble protein, or cell wall dry weight, corresponding to the region of
      continued elongation. Treatment with fluridone progressively inhibited the
      increase in activity with distance from the apex, correlating with the pattern of
      inhibition of elongation. Added ABA partly restored activity at all positions.
      The increase in XET activity at low [psi]w was due to maintenance of the rate of
      deposition of activity despite decreased deposition of wall material. The loss of
      activity associated with decreased ABA was due to inhibition of the deposition of
      activity. The results demonstrate that increased XET activity is associated with
      maintenance of root elongation at low [psi]w and that this response requires
      increased ABA.

PMID- 12232356
TI  - Characterization of Flavonoid 3[prime],5[prime]-Hydroxylase in Microsomal
      Membrane Fraction of Petunia hybrida Flowers.
AB  - We have detected a flavonoid 3[prime],5[prime]-hydroxylase (F3[prime],5[prime]H)
      in the microsomal fraction of Petunia hybrida flowers. Activity varied with the
      development of flowers, peaking immediately prior to and during anthesis, but was
      absent in mature flowers. F3[prime],5[prime]H activity in flower extracts from
      genetically defined floral color mutants correlated strictly with the genotypes
      Hf1 and Hf2. No activity was detected in flowers from mutants homozygous
      recessive for both alleles. F3[prime],5[prime]H activity was dependent on NADPH
      and molecular oxygen; there was only slight activity with NADH. The enzyme
      catalyzes the hydroxylation of 5,7,4[prime]-trihydroxyflavonone at the 3[prime]
      and 5[prime] positions, and of 5,7,3[prime],4[prime]-tetrahydroxyflavonone and
      dihydroquercetin at the 5[prime] position. Hydroxylase activity was inhibited by
      plant growth regulators (1-aminobenzotriazole and tetcyclacis) and by CO, N
      ethylmaleimide, diethyldithiocarbamate, and cytochrome (Cyt) c. Activity was not
      affected by diethylpyrocarbonate or phenylmethylsulfonyl fluoride, but was
      enhanced by 2-mercaptoethanol. A polyclonal antibody that inhibits higher plant
      NADPH-Cyt P450 reductase inhibited the F3[prime],5[prime]H. The data are
      consistent with the suggestion that the P. hybrida F3[prime],5[prime]H is a
      monooxygenase consisting of a Cyt P450 and a NADPH-Cyt P-450 reductase. Cyts P450
      were detected in microsomal membranes and in solubilized detergent extracts of
      these membranes. F3[prime],5[prime]H activity was sensitive to low concentrations
      of all detergents tested, and therefore solubilization of the active enzyme was
      not achieved. Reaction products other than flavanones were observed in
      F3[prime],5[prime]H assays and these may be formed by enzymic oxidation of
      flavanones. The possibility of a microsomal flavone synthase of a type that has
      not been described in P. hybrida is discussed.

PMID- 12232355
TI  - Purification and Characterization of Cinnamoyl-Coenzyme A:NADP Oxidoreductase in
      Eucalyptus gunnii.
AB  - Cinnamoyl-coenzyme A:NADP oxidoreductase (CCR, EC 1.2.1.44), the entry-point
      enzyme into the monolignol biosynthetic pathway, was purified to apparent
      electrophoretic homogeneity from differentiating xylem of Eucalyptus gunnii Hook.
      The purified protein is a monomer of 38 kD and has an isoelectric point of 7.
      Although Eucalyptus gunnii CCR has approximately equal affinities for all
      possible substrates (p-coumaroyl-coenzyme A, feruloyl-coenzyme A, and sinapoyl
      coenzyme A), it is approximately three times more effective at converting
      feruloyl-coenzyme A than the other substrates. To gain a better understanding of
      the catalytic regulation of Eucalyptus CCR, a variety of compounds were tested to
      determine their effect on CCR activity. CCR activity is inhibited by NADP and
      coenzyme A. Effectors that bind lysine and cysteine residues also inhibit CCR
      activity. As a prerequisite to the study of the regulation of CCR at the
      molecular level, polyclonal antibodies were obtained.

PMID- 12232357
TI  - Transient Cl- and K+ Currents during the Action Potential in Chara inflata
      (Effects of External Sorbitol, Cations, and Ion Channel Blockers).
AB  - In voltage-clamp experiments, a two-pulse procedure was used to investigate the
      ionic currents underlying the action potential in Chara inflata. A prepulse
      hyperpolarized the membrane from a resting potential of about -100 to -200 mV.
      The prepulse was followed by a second pulse that changed the potential difference
      (p.d.) to -100 mV and less negative values in steps of 20 mV. This two-pulse
      procedure induces action potentials that have a reproducible time course, which
      is essential for any comparative investigation of the action potential. The two
      pulse procedure reveals that in the charophyte C. inflata the electric current
      flowing across the cell membranes during positive voltage-clamp steps from the
      resting p.d. consists of a leak current flowing from the start of the pulse,
      followed by a transient inward-going current, Ii, commencing after a delay, and
      preceding a delayed transient outward current, Io. The characteristics of the
      current components and their response to various ion channel blockers and ionic
      treatments suggest that: (a) Ii, which is blocked by the external application of
      9-anthracenecarboxylic acid, is carried by Cl- and (b) Io, which is blocked by
      the external application of the organic anions tetraethylammonium (TEA+) and
      nonyltriethylammonium, is carried mainly by K+. The magnitude and behavior of
      these K+ and Cl- currents could be modified by changes in the external
      concentration of CaCl2, LiCl, or NaCl but not sorbitol. Hence, it is concluded
      that NaCl-enhanced transient inward Cl- current, Ii, is due to ionic effects of
      NaCl rather than to its osmotic effects. The modification of the K+ current, Io,
      either by changing external K+ concentrations or by blocking the current with
      TEA+, also alters the Cl- currents Ii.

PMID- 12232358
TI  - Photosynthetic Acclimation in Pea and Soybean to High Atmospheric CO2 Partial
      Pressure.
AB  - Nonnodulated pea (Pisum sativum L. cv Frosty) and soybean (Glycine max [L.] Merr.
      cv Wye) plants were grown under artificial lights from germination with ample
      nutrients, 600 [mu]mol photons m-2 s-1, and either 34 to 36 (control) or 64 to 68
      Pa (enriched) CO2. For soybean, pod removal and whole-plant shading treatments
      were used to alter the source-sink balance and carbohydrate status of the plants.
      Growth of both species was substantially increased by CO2 enrichment despite some
      down-regulation of photosynthesis rate per unit leaf area ("acclimation").
      Acclimation was observed in young pea leaves but not old and in old soybean
      leaves but not young. Acclimation was neither evident in quantum yield nor was it
      related to triose phosphate limitation of net photosynthesis. A correlation
      between levels of starch and sugars in the leaf and the amount of acclimation was
      apparent but was loose and only weakly related to the source-sink balance of the
      plant. A consistent feature of acclimation was reduced ribulose bisphosphate
      carboxylase (RuBPCase) content, although in vivo RuBPCase activity was not
      necessarily diminished by elevated growth CO2 owing to increased percentage of
      activation of the enzyme. A proposal is discussed that the complexity of
      photosynthetic acclimation responses to elevated CO2 is as an expression of re
      optimization of deployment of within-plant resources at three levels of
      competition.

PMID- 12232360
TI  - CO2 Uptake and Electron Transport Rates in Wild-Type and a Starchless Mutant of
      Nicotiana sylvestris (The Role and Regulation of Starch Synthesis at Saturating
      CO2 Concentrations).
AB  - CO2 uptake rate, chlorophyll fluorescence, and 830-nm absorbance were measured in
      wild-type (wt) Nicotiana sylvestris (Speg. et Comes) and starchless mutant NS 458
      leaves at different light intensities and CO2 concentrations. Initial slopes of
      the relationships between CO2 uptake and light and CO2 were similar, but the
      maximum rate at CO2 and light saturation was only 30% in the mutant compared with
      the wt. O2 enhancement of photosynthesis at CO2 and light saturation was
      relatively much greater in the mutant than in the wt. In 21% O2, the electron
      transport rate (ETR) calculated from fluorescence peaked near the beginning of
      the CO2 saturation of photosynthesis. With the further increase of CO2
      concentration ETR remained nearly constant or declined a little in the wt but
      drastically declined in the mutant. Absorbance measurements at 830 nm indicated
      photosystem I acceptor side reduction in both plants at saturating CO2 and light.
      Assimilatory charge (postillumination CO2 uptake) measurements indicated trapping
      of chloroplast inorganic phosphate, supposedly in hexose phosphates, in the
      mutant. It is concluded that starch synthesis gradually substitutes for
      photorespiration as electron acceptor with increasing CO2 concentration in the wt
      but not in the mutant. It is suggested that starch synthesis is co-controlled by
      the activity of the chloroplast fructose bisphosphatase.

PMID- 12232359
TI  - Nuclear Mutation Inhibits Expression of the Chloroplast Gene That Encodes the
      Large Subunit of Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase.
AB  - Chlamydomonas reinhardtii mutant 76-5EN was recovered as a light-sensitive,
      acetate-requiring strain that failed to complement a chloroplast structural gene
      mutant of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco; EC 4.1.1.39).
      Further genetic analysis revealed that the new mutation was inherited in a
      mendelian pattern, indicating that it resides within the nucleus. The 76-5EN
      mutant lacks Rubisco holoenzyme but has wild-type levels of whole-chain electron
      transport activity and chlorophyll. During a 1-min pulse labeling with 35SO42-,
      little or no Rubisco large-subunit synthesis occurred in the mutant. Nuclear
      encoded small subunits were synthesized to a normal level and were subsequently
      degraded. When analyzed by northern hybridization, the 76-5EN mutant was found to
      have a decreased level of large-subunit mRNA. Large-subunit mRNA synthesis also
      appeared to be reduced during a 10-min pulse labeling with [32P]orthophosphate,
      but the labeled mRNA was stable during a 1-h chase. These results indicate that a
      nuclear gene mutation specifically disrupts the accumulation of large-subunit
      mRNA within the chloroplast. A deeper understanding of the nature of the 76-5EN
      gene may be useful for manipulating the expression of the agronomically important
      Rubisco enzyme.

PMID- 12232361
TI  - Partitioning of the Leaf CO2 Exchange into Components Using CO2 Exchange and
      Fluorescence Measurements.
AB  - Photorespiration was calculated from chlorophyll fluorescence and ribulose-1,5
      bisphosphate carboxylase/oxygenase (Rubisco) kinetics and compared with CO2
      evolution rate in the light, measured by three gas-exchange methods in mature
      sunflower (Helianthus annuus L.) leaves. The gas-exchange methods were (a)
      postillumination CO2 burst at unchanged CO2 concentration, (b) postillumination
      CO2 burst with simultaneous transfer into CO2-free air, and (c) extrapolation of
      the CO2 uptake to zero CO2 concentration at Rubisco active sites. The steady
      state CO2 compensation point was proportional to O2 concentration, revealing the
      Rubisco specificity coefficient (Ksp) of 86. Electron transport rate (ETR) was
      calculated from fluorescence, and photorespiration rate was calculated from ETR
      using CO2 and O2 concentrations, Ksp, and diffusion resistances. The values of
      the best-fit mesophyll diffusion resistance for CO2 ranged between 0.3 and 0.8 s
      cm-1. Comparison of the gas-exchange and fluorescence data showed that only
      ribulose-1,5-bisphosphate (RuBP) carboxylation and photorespiratory CO2 evolution
      were present at limiting CO2 concentrations. Carboxylation of a substrate other
      than RuBP, in addition to RuBP carboxylation, was detected at high CO2
      concentrations. A simultaneous decarboxylation process not related to RuBP
      oxygenation was also detected at high CO2 concentrations in the light. We propose
      that these processes reflect carboxylation of phosphoenolpyruvate, formed from
      phosphoglyceric acid and the subsequent decarboxylation of malate.

PMID- 12232362
TI  - Comparative Analysis of Short- and Long-Term Changes in Gene Expression Caused by
      Low Water Potential in Potato (Solanum tuberosum) Cell-Suspension Cultures.
AB  - To dissect the cellular response to water stress and compare changes induced as a
      generalized response with those involved in tolerance/acclimation mechanisms, we
      analyzed changes in two-dimensional electrophoretic patterns of in vivo
      [35S]methionine-labeled polypeptides of cultured potato (Solanum tuberosum) cells
      after gradual and long exposure to polyethylene glycol (PEG)- mediated low water
      potential versus those induced in cells abruptly exposed to the same stress
      intensity. Protein synthesis was not inhibited by gradual stress imposition, and
      the expression of 17 proteins was induced in adapted cells. Some polypeptides
      were inducible under mild stress conditions (5% PEG) and accumulated further when
      cells were exposed to a higher stress intensity (10 and 20% PEG). The synthesis
      of another set of polypeptides was up-regulated only when more severe water
      stress conditions were applied, suggesting that plant cells were able to monitor
      different levels of stress intensity and modulate gene expression accordingly. In
      contrast, in potato cells abruptly exposed to 20% PEG, protein synthesis was
      strongly inhibited. Nevertheless, a large set of polypeptides was identified
      whose expression was increased. Most of these polypeptides were not induced in
      adapted cells, but many of them were common to those observed in abscisic acid
      (ABA)-treated cells. These data, along with the finding that cellular ABA content
      increased in PEG-shocked cells but not in PEG-adapted cells, suggested that this
      hormone is mainly involved in the rapid response to stress rather than long-term
      adaptation. A further group of proteins included those induced after long
      exposure to both water stress and shock. Western blot analysis revealed that
      osmotin was one protein belonging to this common group. This class may represent
      induced proteins that accumulate specifically in response to low water potential
      and that are putatively involved in the maintenance of cellular homeostasis under
      prolonged stress.

PMID- 12232363
TI  - Coordinated Transcriptional Regulation of Storage Product Genes in the Maize
      Endosperm.
AB  - We have demonstrated that expression of genes involved in starch and storage
      protein synthesis of the maize (Zea mays L.) endosperm are coordinated. Genetic
      lesions altering synthetic events in one biosynthetic pathway affect expression
      of genes in both pathways. Initial studies focused on shrunken2 (sh2) and
      brittle2 (bt2) mutants because these genes encode subunits of the same enzyme,
      ADP-glucose pyrophosphorylase. Analysis of various sh2- and bt2- mutant alleles
      showed that the most severe mutations also conditioned the largest increase in
      transcripts. The analysis was extended by monitoring the transcripts of the
      genes, shrunken1 (sh1, structural gene for Suc synthase), sh2, bt2, waxy1 (wx1,
      structural gene for starch synthase), and those of the large and small zeins in
      isogenic maize lines at 14, 22, and 30 d postpollination. Endosperms were wild
      type for all of these genes or contained sh1-, sh2-, bt1-, bt2-, opaque2 (o2-),
      or amylose-extender1 (ae1-) dull1 (du1-) wx1- mutations. Transcripts increased
      continually throughout kernel development in the mutants relative to the standard
      W64A used. Variation in the amount of Suc entering the developing seed also
      altered transcript amounts. The results indicate that starch and protein
      biosynthetic genes act in a concerted manner, and both are sensitive to
      mutationally induced differences.

PMID- 12232364
TI  - Cytoplasmic Acidification and Secondary Metabolite Production in Different Plant
      Cell Suspensions (A Comparative Study).
AB  - In this study, a correlation is described between low cytoplasmic pH, measured
      with the fluorescent probes 2[prime],7[prime]-bis-(2-carboxyethyl)-5-(and-6)
      carboxyfluorescein (acetoxymethyl ester) and bis- [3-propyl-5-oxoisoxazol-4
      yl]pentamethine oxonol, and the production of secondary metabolites for several
      plant cell-suspension systems. Anthraquinone production in Morinda citrifolia
      suspensions is negligible in the presence of 2,4-dichlorophenoxyacetic acid (2,4
      D), whereas with naphthalene acetic acid (NAA) a significant accumulation is
      realized. NAA-grown cells showed a lower cytoplasmic pH than did 2,4-D-grown
      cells. Addition of 2,4-D or parachlorophenoxy acetic acid to NAA-grown cells
      resulted in an inhibition of anthraquinone production and an increase of the
      cytoplasmic pH, whereas addition of parachlorophenyl acetic acid had no effect on
      either parameter. Lignin production in Petunia hybrida cells could be induced by
      subculturing them in a medium without iron. These cells showed a lower
      cytoplasmic pH than control cells. Addition of Fe3+ led to a decreased lignin
      content and an increased cytoplasmic pH. Two cell lines of Linum flavum showed a
      different level of coniferin and lignin concentration in their cells. Cells that
      accumulated coniferin and lignin had a lower cytoplasmic pH than cells that did
      not accumulate these secondary metabolites. Apparently, in different species and
      after different kinds of treatment there is a correlation between acidification
      of the cytoplasm and the production of different secondary metabolites. The
      possible role of this acidification in secondary metabolite production is
      discussed.

PMID- 12232365
TI  - Direct Measurement of ATP-Dependent Proton Concentration Changes and
      Characterization of a K+-Stimulated ATPase in Pea Chloroplast Inner Envelope
      Vesicles.
AB  - Inner envelope membrane vesicles prepared from pea (Pisum sativum L. var Laxton's
      Progress No. 9) chloroplasts have K+-stimulated ATPase activity with a pH optimum
      of 8.4. ATP addition to inner envelope vesicles loaded with pyranine caused a
      decrease in pyranine fluorescence that was consistent with internal
      acidification. The transmembrane pH change induced by the addition of 5 mM ATP
      was about 0.4 unit. Measurement of phosphate released by ATP hydrolysis
      paralleled the pH change, indicating that intravesicular acidification was linked
      to ATPase activity. Vanadate, molybdate, N-ethylmaleimide, and dithiothreitol
      inhibited ATP-dependent vesicle acidification completely, whereas ATPase activity
      was only partially inhibited. These data indicate that pea chloroplast inner
      envelope vesicles contain a proton translocating ATPase and that the pyranine
      loading method can be utilized to study directly ATP-dependent H+ transport
      across these membranes.

PMID- 12232366
TI  - Correlation of Pectin Methylesterase Activity in Root Caps of Pea with Root
      Border Cell Separation.
AB  - We tested predictions of the hypothesis that pectin methylesterase in the root
      cap plays a role in cell wall solubilization leading to separation of root border
      cells from the root tip. Root cap pectin methylesterase activity was detected
      only in species that release large numbers of border cells daily. In pea (Pisum
      sativum) root caps, enzyme activity is correlated with border cell separation
      during development: 6-fold more activity occurs during border cell separation
      than after cell separation is complete. Higher levels of enzyme activity are
      restored by experimental induction of border cell separation. A corresponding
      increase in transcription of a gene encoding root cap pectin methylesterase
      precedes the increase in enzyme activity. A dramatic increase in the level of
      soluble, de-esterified pectin in the root tip also is correlated with pectin
      methylesterase activity during border cell development. This increase in acidic,
      de-esterified pectin during development occurs in parallel with a decrease in
      cell wall/apoplastic pH of cells in the periphery of the root cap.

PMID- 12232367
TI  - Evidence for a Transient Association of New Proteins with the Spirulina maxima
      Phycobilisome in Relation to Light Intensity.
AB  - Environmental parameters are known to affect phycobilisomes. Variations of their
      structure and relative composition in phycobiliproteins have been observed. We
      studied the effect of irradiance variations on the phycobilisome structure in the
      cyanobacterium Spirulina maxima and discovered the appearance of new polypeptides
      associated with the phycobilisomes under an increased light intensity. In high
      light, the six rods of phycocyanin associated with the central core of
      allophycocyanin contained only one to two phycocyanin hexamers instead of the two
      to three they contained in low light. The concomitant disappearance of a 33-kD
      linker polypeptide was observed. Moreover, in high light three polypeptides of
      29, 30, and 47 kD, clearly unrelated to linkers, were found to be associated with
      the phycobilisome fraction: protein labeling showed that a specific association
      of these polypeptides was induced by high light. One polypeptide, at least, would
      play the role of a chaperone protein. Not only the synthesis of these proteins,
      which appeared slightly increased in high light, but also their association with
      phycobilisome structure are light intensity dependent.

PMID- 12232368
TI  - The Effects of Excess Irradiance on Photosynthesis in the Marine Diatom
      Phaeodactylum tricornutum.
AB  - The response of Phaeodactylum tricornutum to excess light was remarkably similar
      to that observed in higher plants and green algae and was characterized by
      complex changes in minimal fluorescence yields of fully dark-adapted samples and
      declines in maximum variable fluorescence levels and oxygen evolution rates. In
      our study the parallel decreases in the effective rate constant for photosystem
      II (PSII) photochemistry, the variable fluorescence yield of a dark-adapted
      sample, and light-limited O2 evolution rates after short (0-10 min) exposures to
      photoinhibitory conditions could not be attributed to damage or down-regulation
      of PSII reaction centers. Instead, these changes were consistent with the
      presence of nonphotochemical quenching of PSII excitation energy in the antennae.
      This quenching was analogous to that component of nonphotochemical quenching
      studied in higher plants that is associated with photoinhibition of
      photosynthesis and/or processes protecting against photoinhibition in that it did
      not relax readily in the dark and persisted in the absence of a bulk
      transthylakoid proton gradient. The quenching was most likely associated with
      photoprotective processes in the PSII antenna that reduced the extent of
      photoinhibitory damage, particularly after longer exposures. Our results suggest
      that a large population of damaged, slowly recovering PSII centers did not form
      in Phaeodactylum even after 60 min of exposure to excess actinic light.

PMID- 12232369
TI  - Posttranslational Regulation of Nitrate Reductase in Higher Plants.

PMID- 12232370
TI  - Cell Cycle Regulation in Plants.

PMID- 12232371
TI  - Assembly of the Light-Harvesting Complexes (LHCs) of Photosystem II (Monomeric
      LHC IIb Complexes Are Intermediates in the Formation of Oligomeric LHC IIb
      Complexes).
AB  - The light-induced assembly of light-harvesting complex (LHC) II has been followed
      during the biogenesis of the plastid. Seedlings grown in intermittent light (IML)
      accumulate only small amounts of chlorophyll b. The minor LHC II apoproteins are
      present; however, the apoprotein levels of the major LHC II complex, LHC IIb, are
      severely depressed after exposure to IML. The levels of all LHC II apoproteins
      increase rapidly upon exposure to continuous illumination. The 25-kD, type 3 LHC
      IIb subunit appears to be more abundant during the early hours of greening in
      relation to its level in mature thylakoids. The LHC IIb apoproteins are initially
      associated with pigments to form monomeric pigment-protein complexes. The
      abundance of monomeric LHC IIb complexes gradually decreases during exposure to
      continuous light and a concomitant increase occurs in the amount of the trimeric
      and higher-order oligomeric forms. Pulse-chase experiments verify that labeled
      LHC IIb monomeric complexes are intermediates in the formation of trimeric and
      higher-order oligomeric LHC IIb-pigmented complexes. Therefore, the assembly of
      LHC II occurs via the initial pigmentation of the apoproteins to form monomeric
      complexes and proceeds in a sequential manner.

PMID- 12232372
TI  - Organization of the Light-Harvesting Complex of Photosystem I and Its Assembly
      during Plastid Development.
AB  - Photosystem I (PSI) holocomplexes were fractionated to study the organization of
      the light-harvesting complex I (LHC I) pigment-proteins in barley (Hordeum
      vulgare) plastids. LHC Ia and LHC Ib can be isolated as oligomeric, presumably
      trimeric, pigment-protein complexes. The LHC Ia oligomeric complex contains both
      the 24- and the 21.5-kD apoproteins encoded by the Lhca3 and Lhca2 genes and is
      slightly larger than the oligomeric LHC Ib complex containing the Lhca1 and Lhca4
      gene products of 21 and 20 kD. The synthesis and assembly of LHC I during light
      driven development of intermittent light-grown plants occurs rapidly upon
      exposure to continuous illumination. Complete PSI complexes are detected by
      nondenaturing Deriphat (disodium N-dodecyl-[beta]-iminodipropionate-160)-PAGE
      after 2 h of illumination, and their appearance correlates with that of the 730-
      to 740-nm emission characteristic of assembled LHC I. However, the majority of
      the newly synthesized LHC I apoproteins are present as monomeric complexes in the
      thylakoids during the early hours of greening. We propose that during development
      of the protochloroplast the LHC I apoproteins are first assembled into monomeric
      pigmented complexes that then aggregate into trimers before becoming attached to
      the pre-existing core complex to form a complete PSI holocomplex.

PMID- 12232373
TI  - The Three-Dimensional Structure of Pectate Lyase E, a Plant Virulence Factor from
      Erwinia chrysanthemi.
AB  - The three-dimensional structure of pectate lyase E (PelE) has been determined by
      crystallographic techniques at a resolution of 2.2 A. The model includes all 355
      amino acids but no solvent, and refines to a crystallographic refinement factor
      of 20.6%. The polypeptide backbone folds into a large right-handed cylinder,
      termed a parallel [beta] helix. Loops of various sizes and conformations protrude
      from the central helix and probably confer function. A putative Ca2+-binding site
      as well as two cationic sites have been deduced from the location of heavy atom
      derivatives. Comparison of the PelE and recently determined pectate lyase C
      (PelC) structures has led to identification of a putative polygalacturonate
      binding region in PelE. Structural differences relevant to differences in the
      enzymatic mechanism and maceration properties of PelE and PelC have been
      identified. The comparative analysis also reveals a large degree of structural
      conservation of surface loops in one region as well as an apparent aromatic
      specificity pocket in the amino-terminal branch. Also discussed is the sequence
      and possible functional relationship of the pectate lyases with pollen and style
      plant proteins.

PMID- 12232374
TI  - Biphasic Stimulation of Translational Activity Correlates with Induction of
      Translation Elongation Factor 1 Subunit [alpha] upon Wounding in Potato Tubers.
AB  - Potato (Solanum tuberosum) tubers exhibit an increase in translational activity
      in response to mechanical wounding. The response is biphasic, with an initial
      stimulation apparent within the first 2 h after wounding and a second increase
      occurring 12 to 24 h after wounding. Increased activity is apparent by
      measurement of protein synthesis both in vivo and in vitro using a cell-free
      extract. Accumulation of the translational elongation factor 1 subunit [alpha]
      (EF-1[alpha]) parallels translational activity. Changes in the steady-state level
      of EF-1[alpha] mRNA, and expression of a chimeric EF-1[alpha] promoter/[beta]
      glucuronidase construct in transgenic potato tubers, indicate that the gene
      encoding EF-1[alpha] is transcribed during both periods of translational
      stimulation. These results indicate that stimulation of translational activity is
      coordinated with increased expression and accumulation of translation factors.

PMID- 12232375
TI  - Light Stress and Oxidative Cell Damage in Photoautotrophic Cell Suspension of
      Euphorbia characias L.
AB  - A photoautotrophic cell-suspension culture of Euphorbia characias L. grown at 70
      [mu]mol photons m-2 s-1 was very sensitive to light stress: the gross
      photosynthesis measured by using a mass spectrometric 16O2/18O2 isotope technique
      showed a fast decrease at a rather low light intensity of 100 [mu]mol photons m-2
      s-1, far below the photosynthetic saturation level. The contribution of activated
      oxygen species on photosystem II photoinhibition was examined for a given light
      intensity. A protective effect on gross photosynthesis was observed with 1%
      oxygen. When light stress was applied to a methyl viologen-adapted cell
      suspension, photoinhibition was reduced. When 50 [mu]mol L-1 methyl viologen was
      added, photoinhibition was slightly enhanced. These responses suggested an
      involvement of superoxide radicals in the photoinhibition process of E. characias
      photoautotrophic cells. The long-term (16 h) effects of photoinhibition were then
      studied. Aldehyde (malondialdehyde and 4-hydroxyalcenals) production resulting
      from lipid peroxidation was stimulated in long-term stressed cells. When 50
      [mu]mol L-1 methyl viologen were added, increased aldehyde production was
      measured. Under 1% oxygen, the aldehyde production was comparable to that of
      nonstressed cells. The relationship among lipid peroxidation, light intensity,
      and net photosynthesis suggests that aldehyde production may result from cell
      death provoked by a prolonged energy deficit due to the inhibition of
      photosynthesis.

PMID- 12232376
TI  - The Role of Oxygen in the Regulation of Nitrogenase Activity in Drought-Stressed
      Soybean Nodules.
AB  - The aim of this study was to investigate the mechanism of nitrogenase inhibition
      in drought-stressed soybean (Glycine max L.) nodules to determine whether this
      stress was similar to other inhibitory treatments (e.g. detopping) known to cause
      an O2 limitation of nodule metabolism. Nodulated soybean plants were either
      detopped or subjected to mild, moderate, or severe drought stress by growth in
      different media and by withholding water for different periods. All treatments
      caused a decline in nitrogenase activity, and in the drought-stressed nodules,
      the decline was correlated with more negative nodule water potentials. Increases
      in rhizosphere O2 concentration stimulated nitrogenase activity much more in
      detopped plants than in drought-stressed plants, reflecting a greater degree of
      O2 limitation with the detopped treatment than with the drought-stressed
      treatment. These results indicated that drought stress differs from many other
      inhibitory treatments, such as detopping, in that its primary cause is not a
      decrease in nodule permeability and a greater O2 limitation of nodule metabolism.
      Rather, drought stress seems to cause a decrease in the maximum O2-sufficient
      rate of nodule respiration or nitrogenase activity, and the changes in nodule
      permeability reported to occur in drought-stressed nodules may be a response to
      elevated O2 concentrations in the infected cell that may occur as nodule
      respiration declines.

PMID- 12232377
TI  - Aluminum-Induced Rapid Root Inhibition and Changes in Cell-Wall Components of
      Squash Seedlings.
AB  - Growth of squash (Cucurbita maxima Duch.) roots was significantly inhibited by 1
      mM AlCl3 as early as 1 h after the treatment. The growth inhibition was confined
      to the elongating zone (1-6 mm from the root tip). Chemical analysis of cell-wall
      polysaccharides from roots revealed that aluminum increased pectin, hemi
      cellulose, and cellulose contents after 3 h of treatment. The effect of aluminum
      on pectin content was found in the elongating zone including the root tip,
      whereas change in cellulose content was confined to only nonelongating zones.
      Hemicellulose content increased in all of the regions along the root axis. The
      increase in the pectin fraction was due to the increases in uronic acids,
      galactose, and arabinose constituents, whereas hemicellulose content changed due
      to increases in glucose, xylose, galactose, and arabinose. The results clearly
      indicate that aluminum rapidly reduced squash root growth by inhibiting cell
      elongation and altering metabolism of cell-wall polysaccharides in the
      nonelongating zone as well as in the elongating zone.

PMID- 12232378
TI  - Effects of a Short-Term Shift to Low Temperature and of Long-Term Cold Hardening
      on Photosynthesis and Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase and Sucrose
      Phosphate Synthase Activity in Leaves of Winter Rye (Secale cereale L.).
AB  - The effect of a short-term (hours) shift to low temperature (5[deg]C) and long
      term (months) cold hardening on photosynthesis and carbon metabolism was studied
      in winter rye (Secale cereale L. cv Musketeer). Cold-hardened plants grown at
      5[deg]C exhibited 25% higher in situ CO2 exchange rates than nonhardened plants
      grown at 24[deg]C. Cold-hardened plants maintained these high rates throughout
      the day, in contrast to nonhardened plants, which showed a gradual decline in
      photosynthesis after 3 h. Associated with the increase in photosynthetic capacity
      following cold hardening was an increase in ribulose-1,5-bisphosphate
      carboxylase/oxygenase and sucrose phosphate synthase activity and 3- to 4-fold
      increases in the pools of associated metabolites. Leaves of nonhardened plants
      shifted overnight to 5[deg]C required 9 h in the light at 5[deg]C before maximum
      rates of photosynthesis were reached. The gradual increase in photosynthesis in
      leaves shifted to 5[deg]C was correlated with a sharp decline in the 3
      phosphoglycerate/triose phosphate ratio and by an increase in the ribulose
      bisphosphate/3-phosphoglycerate ratio, indicating the gradual easing of
      aninorganic phosphate-mediated feedback inhibition on photo-synthesis. We suggest
      that the strong recovery of photosynthesis in winter rye following cold hardening
      indicates that the buildup of photosynthetic enzymes, as well as those involved
      in sucrose synthesis, is an adaptive response that enables these plants to
      maximize the production of sugars that have both cryoprotective and storage
      functions that are critical to the performance of these cultivars during over
      wintering.

PMID- 12232379
TI  - Kinetics Analysis of the Plasma Membrane Sucrose-H+ Symporter from Sugar Beet
      (Beta vulgaris L.) Leaves.
AB  - The kinetics behavior of the H+-sucrose (Suc) symporter was investigated in
      plasma membrane vesicles from sugar beet (Beta vulgaris L.) leaves by analyzing
      the effect of external and internal pH (pHo and pHi, respectively) on Suc uptake.
      The apparent Km for Suc uptake increased 18-fold as the pHo increased from 5.5 to
      7.5. Over this same pHo range, the apparent Vmax for Suc uptake remained
      constant. The effects of pHi in the presence or absence of internal Suc were
      exclusively restricted to changes in Vmax. Thus, proton concentration on the
      inside of the membrane vesicles ([H+]i) behaved as a noncompetitive inhibitor of
      Suc uptake. The Km for the proton concentration on the outside of the membrane
      vesicles was estimated to be pH 6.3, which would indicate that at physiological
      apoplastic pH Suc transport might be sensitive to changes in pHo. On the other
      hand, the [H+]i for half-maximal inhibition of Suc uptake was approximately pH
      5.4, making regulation of Suc transport through changes in [H+]i unlikely. These
      results were interpreted in the framework of the kinetics models for co-transport
      systems developed by D. Sanders, U.-P. Hansen, D. Gradmann, and C. L. Slayman (J
      Membr Biol [1984] 77: 123-152). Based on their analysis, the behavior of the Suc
      symporter with respect to the [H+]i is interpreted as an ordered binding
      mechanism by which the binding of Suc on the apoplastic side of the membrane and
      its release on the symplastic side precedes that of H+ (i.e. a first-on, first
      off model).

PMID- 12232380
TI  - Regulation of Oleoresinosis in Grand Fir (Abies grandis) (Coordinate Induction of
      Monoterpene and Diterpene Cyclases and Two Cytochrome P450-Dependent Diterpenoid
      Hydroxylases by Stem Wounding).
AB  - Oleoresin (pitch) is a defensive secretion composed of monoterpene olefins
      (turpentine) and diterpene resin acids (rosin) that is produced in grand fir
      (Abies grandis Lindl.) stems in response to wounding. Monoterpene and diterpene
      biosynthesis are coordinately induced in wounded stems as determined by
      monitoring the activity of monoterpene and diterpene cyclases, as well as two
      cytochrome P450-dependent diterpenoid hydroxylases involved in the formation of
      ([mdash])-abietic acid, the principal resin acid of this species. The activity of
      these enzymes reaches maximum levels that are 5- to 100-fold higher than those of
      nowwounded control stems 10 d after wounding and this is followed by a
      synchronous decline. The increase in biosynthetic activity is consequently
      followed by the accumulation of a viscous mass of resin acids, with the loss of
      the volatile monoterpenes, at the site of injury. The observed coordinate
      induction of monoterpene olefin and abietic acid bio-synthesis and the results of
      oleoresin analysis are consistent with the role of the volatile monoterpenes as a
      solvent for the mobilization and deposition of resin acids at the wound site to
      seal the injury with a rosin barrier after the evaporation of the turpentine. The
      last step of resin acid biosynthesis is catalyzed by an operationally soluble
      aldehyde dehydrogenase that is not inducible by wounding but seemingly is
      expressed constitutively at a high level. In vivo [14C]acetate feeding and resin
      analysis indicate that this enzyme is not efficiently coupled to the earlier
      steps of the pathway.

PMID- 12232381
TI  - Ozone, Sulfur Dioxide, and Ultraviolet B Have Similar Effects on mRNA
      Accumulation of Antioxidant Genes in Nicotiana plumbaginifolia L.
AB  - We have studied the expression of antioxidant genes in response to near ambient
      conditions of O3, SO2, and ultraviolet B (UV-B) in Nicotiana plumbaginifolia L.
      The genes analyzed encode four different superoxide dismutases (SODs), three
      catalases (Cat1, Cat2, and Cat3), the cytosolic ascorbate peroxidase (cyt APx),
      and glutathione peroxidase (GPx). The experimental setup for each treatment was
      essentially the same and caused no visible damage, thus allowing direct
      comparison of the different stress responses. Our data showed that the effects of
      O3, SO2, and UV-B on the antioxidant genes are very similar, although the
      response to SO2 is generally less pronounced and delayed. The effects of the
      different stresses are characterized by a decline in Cat1, a moderate increase in
      Cat3, and a strong increase in Cat2 and GPx. Remarkably, SODs and cyt APx were
      not affected. Analysis of SOD and APx expression in the ozone-sensitive Nicotiana
      tabacum L. cv PBD6 revealed that induction of the cytosolic copper/zinc SOD and
      cyt APx occurs only with the onset of visible damage. It is proposed that
      alterations in mRNA levels of catalases and GPx, but not of SODs and cyt APx,
      form part of the initial antioxidant response to O3, SO2, and UV-B in Nicotiana.

PMID- 12232382
TI  - Differential Transcript Levels of Genes Associated with Glycolysis and Alcohol
      Fermentation in Rice Plants (Oryza sativa L.) under Submergence Stress.
AB  - Expression of genes encoding enzymes involved in specialized metabolic pathways
      is assumed to be regulated coordinately to maintain homeostasis in plant cells.
      We analyzed transcript levels of rice (Oryza sativa L.) genes associated with
      glycolysis and alcohol fermentation under submergence stress. When each
      transcript was quantified at several times, two types (I and II) of mRNA
      accumulation were observed in response to submergence stress. Transcripts of type
      I genes reached a maximum after 24 h of submergence and were reduced by transfer
      to aerobic conditions or by partial exposure of shoot tips to air. In a
      submergence-tolerant rice cultivar, transcript amounts of several type I genes,
      such as glucose phosphate isomerase, phosphofructokinase, glyceraldehyde
      phosphate dehydrogenase, and enolase, increased significantly compared to an
      intolerant cultivar after 24 h of submergence. This suggests that the mRNA
      accumulation of type I genes increases in response to anaerobic stress. mRNA
      accumulation of type II genes, such as aldolase and pyruvate kinase, reached a
      maximum after 10 h of submergence. Following transfer to aerobic conditions,
      their transcript levels were not so rapidly decreased as were type I genes. These
      results suggest that the mRNA levels of genes engaged in glycolysis and alcohol
      fermentation may be regulated differentially under submergence stress.

PMID- 12232383
TI  - Proton-Peptide Co-Transport in Broad Bean Leaf Tissues.
AB  - The transport of [14C]glycyl-glycine (Gly-Gly) has been characterized in leaf
      discs from mature exporting leaves of broad bean (Vicia faba L.). In terms of
      glycine (Gly) equivalents, the rate of transport of Gly-Gly was similar to that
      of Gly uptake. Uptake of Gly-Gly was localized mainly in the mesophyll cells,
      with little accumulation in the veins. It was optimal at pH 6.0, sensitive to
      thiol reagents and metabolic inhibitors, and exhibited a single saturable phase
      with an apparent Michaelis constant of 16 mM. Gly-Gly did not inhibit the uptake
      of labeled Gly. Addition of Gly-Gly induced a concentration-dependent pH rise in
      the medium, showing that peptide uptake is mediated with proton co-transport. Gly
      Gly also induced a concentration-dependent transmembrane depolarization of
      mesophyll cells with an apparent Michaelis constant of 15 mM. This depolarization
      was followed by a transient hyperpolarization. When present at a 10-fold excess,
      various peptides and tripeptides were able to inhibit Gly-Gly uptake with the
      following decreasing order of efficiency: Gly-Gly-Gly = leucine-Gly > Gly
      tyrosine > Gly-glutamine = Gly-glutamic acid > Gly-phenylalanine > Gly-threonine
      > Gly-aspartic acid = Gly-asparagine = aspartic acid-Gly. Gly inhibited the
      uptake of Gly-Gly only slightly, whereas tetraGly and the tripeptide glutathione
      were not inhibitory. The dipeptides inhibiting Gly-Gly uptake also induced
      changes in the transmembrane potential difference of mesophyll cells and were
      able to affect in a complex way the response normally induced by Gly-Gly.
      Altogether, the data demonstrate the existence of a low-affinity, broad
      specificity H+/peptide co-transporter at the plasma membrane of mesophyll cells.
      The physiological importance of this transporter for the exchange of nitrogenous
      compounds in mature leaves remains to be determined, as do the details of the
      electrophysiological events induced by the dipeptides.

PMID- 12232385
TI  - Factors Affecting the Acetylene to 15N2 Conversion Ratio in Root Nodules of
      Myrica gale L.
AB  - When nodules of actinorhizal plants are exposed to acetylene, there is often an
      initial peak rate of acetylene reduction followed by a decline and a partial
      recovery. Treatment of hydroponically grown Myrica gale L. with water deficiency
      or dark stress increased the magnitude of the acetylene-induced decline and
      decreased the extent of the recovery. When N2 fixation was measured with 15N2 in
      unstressed plants, the ratio of acetylene reduction (peak) to N2 fixation prior
      to acetylene exposure was 3.73 [plus or minus] 0.14 (mean [plus or minus] SE).
      This value does not differ significantly (P < 0.05) from the theoretical minimum
      value of 4.0. In water-stressed plants the conversion ratio for the peak rate was
      greater (4.32 [plus or minus] 0.10) and in dark-stressed plants it was lower
      (2.54 [plus or minus] 0.33) than 4.0. The conversion ratio for the recovered rate
      of acetylene reduction was much lower than 4.0 in all cases, with mean values
      ranging from 1.16 to 2.60. We conclude that the peak rate of acetylene reduction
      provides the most reliable estimate of N2 fixation. The recovered rate of
      acetylene reduction consistently underestimates N2 fixation, sometimes severely,
      and thus measurements of acetylene reduction made in closed systems also
      underestimate N2 fixation to varying degrees.

PMID- 12232384
TI  - Sensitivity of Superoxide Dismutase Transcript Levels and Activities to Oxidative
      Stress Is Lower in Mature-Senescent Than in Young Barley Leaves.
AB  - Antioxidant enzyme activities are inducible by oxidative stress and decrease
      during senescence. To determine if the age-dependent decrease of superoxide
      dismutase (SOD) activities is due to decreased sensitivity to oxidative stress,
      we have investigated the changes in steady-state levels of transcripts and
      activities of mitochondrial Mn-SOD (SOD1), chloroplastic Fe-SOD (SOD2), and
      cytoplasmic Cu-Zn-SOD (SOD3) in young and mature-senescent detached barley
      (Hordeum vulgare L.) leaves in response to incubation in darkness, growth light
      (20 W m-2), and photooxidative stress conditions (100 W m-2 with 21 or 100% O2).
      For a comparison, changes in the mRNA for ribulose bisphosphate carboxylase were
      also measured. After leaf detachment, the abundance of all three SOD mRNAs
      increased, then decreased and eventually stabilized after 6 h of incubation.
      After 20 h of incubation under darkness SOD transcripts decreased in both young
      and mature-senescent leaves. While under strong photooxidative stress the levels
      of the three SOD transcripts significantly increased in young leaves; in mature
      senescent leaves SOD2 and, to lesser extent, SOD1 and SOD3 transcripts decreased.
      Generally, SOD activity changes were similar to those of mRNAs. It is proposed
      that oxidative damage during senescence could be favored by the inability of
      senescing leaves to modulate the steady-state level of SOD mRNA, and probably
      those of other antioxidant enzymes, concomitant with the rate of oxyradical
      formation.

PMID- 12232386
TI  - Organization of Photosystem I Polypeptides (A Structural Interaction between the
      PsaD and PsaL Subunits).
AB  - The wild-type, PsaD-less, and PsaL-less strains of the cyanobacterium
      Synechocystis sp. PCC 6803 were used to study subunit interactions in photosystem
      I (PSI). When the membranes of a PsaD-less strain were solubilized with Triton X
      100 and PSI was purified using ion-exchange chromatography and sucrose-gradient
      ultracentrifugation, the PsaL subunit was substantially removed from the core of
      PSI, whereas other subunits, such as PsaE and PsaF, were quantitatively retained
      during purification. When the wild-type PSI was exposed to increasing
      concentrations of NaI, the PsaE, PsaD, and PsaC subunits were gradually removed,
      whereas PsaF, PsaL, PsaK, and PsaJ resisted removal by up to 3 M NaI. The absence
      of PsaL enhanced the accessibility of PsaD to removal by NaI. Treatment of the
      wild-type PSI complexes with glutaraldehyde at 4[deg] C resulted in a 29-kD cross
      linked product between PsaD and PsaL. The formation of such cross-linked species
      was independent of PSI concentrations, suggesting an intracomplex cross-linking
      between PsaD and PsaL. Taken together, these results demonstrate a structural
      interaction between PsaD and PsaL that plays a role in their association with the
      PSI core.

PMID- 12232387
TI  - Aerenchyma Carbon Dioxide Can Be Assimilated in Typha Iatifolia L. Leaves.
AB  - Leaf structural characteristics and gas-exchange measurements were used to
      determine whether photosynthetic tissue of Typha Iatifolia L. (cattail) utilized
      CO2 from the aerenchyma gas spaces, part of an internal pathway for gas transport
      in this wetland species. The partial pressure of CO2 (pCO2) in these aerenchyma
      gas spaces can be more than 10 times atmospheric pCO2. The photosynthetic tissue
      occurred in structurally similar adaxial and abaxial palisades, which were
      distinctly separated from each other by the aerenchyma gas spaces. In each
      palisade there were three to four layers of tightly packed, nonchlorophyllous
      cells separating the photosynthetic tissue from the aerenchyma gas space.
      Different lines of evidence indicated that CO2 conductance in the light was
      significantly greater across the epidermal surface than across the internal
      surface of both palisades. However, at an epidermal pCO2 of 350 [mu]bars and an
      internal pCO2 of 820 [mu]bars, the net rates of CO2 uptake (PN) across the
      epidermal and internal surfaces were about equal. PN across the internal surface
      was greater than across the epidermal surface at higher internal pCO2. Gas space
      pCO2 can be greater than 820 [mu]bars in the field, and therefore, PN across the
      internal surface could be a significant proportion of epidermal surface PN.

PMID- 12232388
TI  - Cytoplasmic Ca2+, K+, Cl-, and NO3- Activities in the Liverwort Conocephalum
      conicum L. at Rest and during Action Potentials.
AB  - Intracellular Ca2+, K+, Cl-, and NO3- activities were measured with ion-selective
      microelectrodes in the liverwort Conocephalum conicum L. at rest, during
      dark/light changes, and in the course of action potentials triggered by light or
      electrical stimuli. The average free cytosolic Ca2+ concentration was 231 [plus
      or minus] 65 nM. We did not observe any light-dependent changes of the free
      cytosolic Ca2+ concentration as long as no action potential was triggered. During
      action potentials, on average a 2-fold increase of the free cytoplasmic Ca2+
      concentration was recorded. Intracellular K+ activity was 76 [plus or minus] 10
      mM. It did not depend on K+ concentration changes in the bath solution between
      0.1 and 10 mM. The average equilibrium potential for K+ in the standard medium
      containing 1 mM K+ was -110 mV, which differed significantly from the resting
      potential of -151 [plus or minus] 2 mV. During action potentials, either a slight
      decrease or no changes in intracellular K+ activity were recorded. The average Cl
      activity was 7.4 [plus or minus] 0.2 mM in the cytoplasm and 43.5 [plus or
      minus] 7 mM in the vacuole. The activities of NO3- were 0.63 [plus or minus] 0.05
      mM in the cytoplasm and 3.0 [plus or minus] 0.3 mM in the vacuole. For both
      anions the vacuolar activity was 5 to 6 times higher than the cytoplasmic
      activity. After the light was switched off both the Cl- and the NO3- activity
      showed either no change or a slight increase. Illumination caused a gradual
      return to previous values or no change. During action potentials a slight
      decrease of intracellular Cl- activity was recorded. It was concluded that in
      Conocephalum, as in characean cells, chloride channels are involved in the
      depolarization phase of the action potentials. We discuss a model for the ion
      fluxes during an action potential in Conocephalum.

PMID- 12232389
TI  - Fumonisin- and AAL-Toxin-Induced Disruption of Sphingolipid Metabolism with
      Accumulation of Free Sphingoid Bases.
AB  - Fumonisins (FB) and AAL-toxin are sphingoid-like compounds produced by several
      species of fungi associated with plant diseases. In animal cells, both fumonisins
      produced by Fusarium moniliforme and AAL-toxin produced by Alternaria alternata
      f. sp. lycopersici inhibit ceramide synthesis, an early biochemical event in the
      animal diseases associated with consumption of F. moniliforme-contaminated corn.
      In duckweed (Lemna pausicostata Heglem. 6746), tomato plants (Lycopersicon
      esculentum Mill), and tobacco callus (Nicotiana tabacum cv Wisconsin), pure FB1
      or AAL-toxin caused a marked elevation of phytosphingosine and sphinganine,
      sphingoid bases normally present in low concentrations. The relative increases
      were quite different in the three plant systems. Nonetheless, disruption of
      sphingolipid metabolism was clearly a common feature in plants exposed to FB1 or
      AAL-toxin. Resistant varieties of tomato (Asc/Asc) were much less sensitive to
      toxin-induced increases in free sphinganine. Because free sphingoid bases are
      precursors to plant "ceramides," their accumulation suggests that the primary
      biochemical lesion is inhibition of de novo ceramide synthesis and reacylation of
      free sphingoid bases. Thus, in plants the disease symptoms associated with A.
      alternata and F. moniliforme infection may be due to disruption of sphingolipid
      metabolism.

PMID- 12232390
TI  - Characterization and Localization of a Phenoloxidase in Mung Bean Hypocotyl Cell
      Walls.
AB  - The occurrence of proteins able to oxidize polyphenols even in the absence of
      H2O2 was recently reported in mung bean (Vigna radiata L.) hypocotyl cell wall
      extracts (R. Goldberg, A. Chabanet, A.M. Catesson [1993] In K.G. Welinder, S.K.
      Rasmussen, C. Penel, H. Greppin, eds, Plant Peroxidases: Biochemistry and
      Physiology, pp. 296-300). Therefore, the possible presence of a laccase in the
      extracts was investigated using immunocytological and biochemical approaches. An
      enzyme catalyzing phenol oxidation in the presence of molecular O2 was extracted
      and purified from the cell walls. This 38-kD cationic protein, like o
      diphenoloxidases, was unable to oxidize p-diphenols or p-diamines. However, it
      crossreacted with an anti-laccase antiserum and, like laccases, its activity was
      inhibited by N-cetyl-N,N,N-trimethylammonium bromide but not by ferulic acid
      salts. Immunolabeling data showed that the 38-kD oxidase was absent from all
      cellulosic cell walls. It was localized only in lignifying and lignified cell
      walls. This restricted localization suggests that this laccase-like phenoloxidase
      could participate in the lignification process but not in the primary wall
      stiffening, which develops in the epidermal and cortical tissues along the mung
      bean hypocotyl.

PMID- 12232391
TI  - Comparison of the Stereospecificity and Immunoreactivity of NADH-Ferricyanide
      Reductases in Plant Membranes.
AB  - The substrate stereospecificity of NADH-ferricyanide reductase activities in the
      inner mitochondrial membrane and peroxisomal membrane of potato (Solanum
      tuberosum L.) tubers, spinach (Spinacea oleracea L.) leaf plasma membrane, and
      red beetroot (Beta vulgaris L.) tonoplast were all specific for the [beta]
      hydrogen of NADH, whereas the reductases in wheat root (Triticum aestivum L.)
      endoplasmic reticulum and potato tuber outer mitochondrial membrane were both
      [alpha]-hydrogen specific. In all isolated membrane fractions one or several
      polypeptides with an apparent size of 45 to 55 kD cross-reacted with antibodies
      raised against a microsomal NADH-ferricyanide reductase on western blots.

PMID- 12232392
TI  - Rapid Uptake of Aluminum into Cells of Intact Soybean Root Tips (A
      Microanalytical Study Using Secondary Ion Mass Spectrometry).
AB  - A wide range of physiological disorders has been reported within the first few
      hours of exposing intact plant roots to moderate levels of Al3+. Past
      microanalytic studies, largely limited to electron probe x-ray microanalysis,
      have been unable to detect intracellular Al in this time frame. This has led to
      the suggestion that Al exerts its effect solely from extracellular or remote
      tissue sites. Here, freeze-dried cryosections (10 [mu]m thick) collected from the
      soybean (Glycine max) primary root tip (0.3-0.8 mm from the apex) were analyzed
      using secondary ion mass spectrometry (SIMS). The high sensitivity of SIMS for Al
      permitted the first direct evidence of early entry of Al into root cells. Al was
      found in cells of the root tip after a 30-min exposure of intact roots to 38
      [mu]M Al3+. The accumulation of Al was greatest in the first 30 [mu]m, i.e. two
      to three cell layers, but elevated Al levels extended at least 150 [mu]m inward
      from the root edge. Intracellular Al concentrations at the root periphery were
      estimated to be about 70 nmol g-1 fresh weight. After 18 h of exposure, Al was
      evident throughout the root cross-section, although the rate of accumulation had
      slowed considerably from that during the initial 30 min. These results are
      consistent with the hypothesis that early effects of Al toxicity at the root
      apex, such as those on cell division, cell extension, or nutrient transport,
      involve the direct intervention of Al on cell function.

PMID- 12232393
TI  - Purification, Characterization, and Submitochondrial Localization of the 32
      Kilodalton NADH Dehydrogenase from Maize.
AB  - Plant mitochondria have the unique ability to directly oxidize exogenous NAD(P)H.
      We recently separated two NAD(P)H dehydrogenase activities from maize (Zea mays
      L.) mitochondria using anion-exchange (Mono Q) chromatography. The first peak of
      activity oxidized only NADH, whereas the second oxidized both NADH and NADPH. In
      this paper we describe the purification of the first peak of activity to a 32-kD
      protein. Polyclonal antibodies to the 32-kD protein were used to show that it was
      present in mitochondria from several plant species. Two-dimensional gel analysis
      of the 32-kD NADH dehydrogenase indicated that it consisted of two major and one
      minor isoelectric forms. Immunoblot analysis of submitochondrial fractions
      indicated that the 32-kD protein was enriched in the soluble protein fraction
      after mitochondrial disruption and fractionation; however, some association with
      the membrane fraction was observed. The membrane-impermeable protein cross
      linking agent 3,3[prime] -dithiobis-(sulfosuccinimidylpropionate) was used to
      further investigate the submitochondrial location of the 32-kD NADH
      dehydrogenase. The 32-kD protein was localized to the outer surface of the inner
      mitochondrial membrane or to the intermembrane space. The pH optimum for the
      enzyme was 7.0. The activity was found to be severely inhibited by p
      chloromercuribenzoic acid, mersalyl, and dicumarol, and stimulated somewhat by
      flavin mononucleotide.

PMID- 12232394
TI  - Alteration of the Amount of the Chloroplast Phosphate Translocator in Transgenic
      Tobacco Affects the Distribution of Assimilate between Starch and Sugar.
AB  - Tobacco plants (Nicotiana tabacum L.) transformed with sense and antisense
      constructs of a cDNA encoding the tobacco phosphate-triose phosphate-3
      phosphoglycerate translocator (phosphate translocator) were shown to contain
      altered amounts of phosphate translocator mRNA and protein. Phosphate
      translocator activity in intact chloroplasts isolated from transformed plants
      showed a 15-fold variation, from 20% of the wild-type activity in antisense
      transformants to 300% of the wild-type activity in sense transformants. However,
      the maximal rates of photosynthesis and the rates of photosynthetic carbon
      assimilation in ambient CO2 showed no consistent differences between
      transformants. Starch content was decreased by 20% and total soluble sugars were
      increased by 20% in leaves of antisense transformants compared to sense
      transformants. The 40% decrease in the ratio of starch to total soluble sugars in
      antisense transformants relative to sense transformants indicates that
      distribution of assimilate between starch and sugar had been altered. However,
      the amount of sucrose in the leaves was unchanged. The changes in total soluble
      sugars were accounted for completely by changes in glucose and fructose,
      suggesting the existence of a homeostatic mechanism for maintaining sucrose
      concentrations in the leaves at the expense of glucose and fructose.

PMID- 12232395
TI  - The H+/Cl- Symporter in Root-Hair Cells of Sinapis alba (An Electrophysiological
      Study Using Ion-Selective Microelectrodes).
AB  - In root-hair cells of Sinapis alba, cytosolic pH, cytosolic [Cl-], membrane
      potential, and membrane resistance have been measured to investigate proton
      driven Cl- transport across the plasma membrane. Rapid lowering of the external
      pH transiently increased cytosolic [Cl-] and acidified the cytoplasm. To an
      abrupt increase in external [Cl-] the cells reacted with a rapid initial
      depolarization and a subsequent slower hyperpolarization, which was accompanied
      by an increase in cytosolic [Cl-] and [H+]. These results are indicative of an
      nH+/Cl- symport with n > 1. Simultaneous recording of the membrane potential, the
      proton motive force, cytosolic pH, and cytosolic [Cl-] reveals that kinetically
      this Cl- transport depends on the pH gradient across the plasma membrane rather
      than on the membrane potential.

PMID- 12232396
TI  - Plastid Class I and Cytosol Class II Aldolase of Euglena gracilis (Purification
      and Characterization).
AB  - The plastidic class I and cytosolic class II aldolases of Euglena gracilis have
      been purified to apparent homogeneity. In autotrophically grown cells, up to 81%
      of the total activity is due to class I activity, whereas in heterotrophically
      grown cells, it is only 7%. The class I aldolase has been purified to a specific
      activity of 20 units/mg protein by anion-exchange chromatography, affinity
      chromatography, and gel filtration. The native enzyme (molecular mass 160 kD)
      consisted of four identical subunits of 40 kD. The class II aldolase was purified
      to a specific activity of 21 units/mg by (NH4)2SO4 fractionation, anion-exchange
      chromatography, chromatography on hydroxylapatite, and gel filtration. The native
      enzyme (molecular mass 80 kD) consisted of two identical subunits of 38 kD. The
      Km (fructose-1,6-bisphosphate) values were 12 [mu]M for the class I enzyme and
      175 [mu]M for the class II enzyme. The class II aldolase was inhibited by 1 mM
      ethylenediaminetetraacetate (EDTA), 0.8 mM cysteine, 0.5 mM Zn2+, or 0.5 mM Cu2+.
      Na+, K+, Rb+, and NH4+ (but not Li+ or Cs+) enhanced the activity up to 7-fold.
      After inactivation by EDTA, the activity could be partially restored by Mn2+,
      Cu2+, or Co2+. A subclassification of class II aldolases is proposed based on (a)
      activation/inhibition by Cys and (b) activation or not by divalent ions.

PMID- 12232397
TI  - Induction and Turnover of Nitrate Reductase in Zea mays (Influence of Light).
AB  - Both light and NO3- are necessary for the appearance of nitrate reductase (NR)
      activity (NRA) in photosynthetic tissues. To define the light effect more
      precisely, we examined the response to light/dark transitions on NRA, NR protein
      (NRP), and NR mRNA in 6-d-old maize (Zea mays cv W64A x W182E) seedlings that had
      been grown in a light/dark regime for 5 d and then induced with 5 mM KNO3 for 24
      h. The decay of NRA and NR mRNA in the shoot was immediate, but there were only
      minor changes in NRP during the initial 4 h in the dark. In root tissues, in
      contrast, there was a 4-h delay in the loss of NRA, NRP, and NR mRNA after
      transfer to the dark. When the seedlings were returned to light after a 2-h
      interval in the dark, shoot NRA reached 92% of the initial levels within 30 min
      of illumination. These results indicate that in the shoots (a) NR message
      production requires light and (b) the NRP that appears with light treatment and
      that is active is inactivated in the dark. The NRP can be reactivated when the
      light is turned on after short periods of darkness (2 h). Root tissues, on the
      other hand, probably respond to the supply of photosynthetically produced
      metabolites rather than to immediate products of the light reactions of
      photosynthesis.

PMID- 12232398
TI  - Immobilized and Free Apoplastic Pectinmethylesterases in Mung Bean Hypocotyl.
AB  - The nature and the action pattern of apoplastic pectinmethylesterase (PME)
      isoforms were investigated in mung bean [Vigna radiata (L.) Wilzeck] hypocotyls.
      Successive extractions of neutral and alkaline PME isoforms present in hypocotyl
      native cell walls (referred to as PE1, PE2, PE3, PE4, with increasingly basic
      isoelectric points) revealed that solubilization of PE1, PE2, and PE4 did not
      induce any significant decrease in the cell-wall-bound PME activity. The in vitro
      de-esterification occurring when isolated cell walls were incubated with pectin
      resulted, then, from the activity of PE3. In addition, pH control of PME activity
      was shown to be much stronger for enzymes bound to cell walls, in their native
      state or reintroduced after solubilization, than for enzymes in solution. Mature
      cell walls showed much more activity than young cell walls, and were relatively
      enriched in two acidic PME isoforms missing in young cell walls. One acidic PME
      was also detected in the extracellular fluid. The acidic and neutral isoforms
      that could be easily transferred from their binding sites to their substrate
      might be those involved in the demethylation process developing along the mung
      bean hypocotyl.

PMID- 12232399
TI  - Acclimation of Respiratory O2 Uptake in Green Tissues of Field-Grown Native
      Species after Long-Term Exposure to Elevated Atmospheric CO2.
AB  - C3 and C4 plants were grown in open-top chambers in the field at two CO2
      concentrations, normal ambient (ambient) and normal ambient + 340 [mu]LL-1
      (elevated). Dark oxygen uptake was measured in leaves and stems using a liquid
      phase Clark-type oxygen electrode. High CO2 treatment decreased dark oxygen
      uptake in stems of Scirpus olneyi (C3) and leaves of Lindera benzoin (C3)
      expressed on either a dry weight or area basis. Respiration of Spartina patens
      (C4) leaves was unaffected by CO2 treatment. Leaf dry weight per unit area was
      unchanged by CO2, but respiration per unit of carbon or per unit of nitrogen was
      decreased in the C3 species grown at high CO2. The component of respiration in
      stems of S. olneyi and leaves of L. benzoin primarily affected by long-term
      exposure to the elevated CO2 treatment was the activity of the cytochrome
      pathway. Elevated CO2 had no effect on activity and capacity of the alternative
      pathway in S. olneyi. The cytochrome c oxidase activity, assayed in a cell-free
      extract, was strongly decreased by growth at high CO2 in stems of S. olneyi but
      it was unaffected in S. patens leaves. The activity of cytochrome c oxidase and
      complex III extracted from mature leaves of L. benzoin was also decreased after
      one growing season of plant exposure to elevated CO2 concentration. These results
      show that in some C3 species respiration will be reduced when plants are grown in
      elevated atmospheric CO2. The possible physiological causes and implications of
      these effects are discussed.

PMID- 12232400
TI  - arc6, A Fertile Arabidopsis Mutant with Only Two Mesophyll Cell Chloroplasts.
AB  - A novel mutant of Arabidopsis thaliana, arc6 (accumulation and replication of
      chloroplasts), has been isolated from a transfer DNA-mutagenized population of
      Arabidopsis seedlings. arc6 has the most extreme arc mutant phenotype we have yet
      described, with only one to three chloroplasts per leaf mesophyll cell compared
      to a mean of 83 in cells of the wild-type var Wassilewskija. The chloroplasts of
      arc6 are 20-fold larger than wild-type chloroplasts.Chloroplast division is
      almost certainly precluded in arc6 mesophyll cells, since chloroplast number per
      cell does not increase during mesophyll cell expansion. arc6 chloroplasts are
      long and thin in cross-section and only one-half the width of wild-type
      chloroplasts and the arrangement of thylakoid membranes is largely unaltered.
      arc6 segregates as a monogenic recessive nuclear mutation in a normal Mendelian
      manner and the arc6 phenotype is stably inherited for at least four generations.
      arc6 plants grow normally and are fertile, although the rosette leaves appear
      curled and twisted. arc6 plants accumulate 70 to 75% of the biomass of wild type.
      The phenotype of this novel mutant is discussed in relation to the nature of the
      control of chloroplast division in leaf cells.

PMID- 12232401
TI  - Metabolic Control of Anaerobic Glycolysis (Overexpression of Lactate
      Dehydrogenase in Transgenic Tomato Roots Supports the Davies-Roberts Hypothesis
      and Points to a Critical Role for Lactate Secretion.
AB  - Roots of all plants examined so far have the potential for both ethanol and
      lactate fermentation. A short burst of lactate fermentation usually occurs when
      plant tissues are transferred from normoxic to anoxic conditions. According to
      the Davies-Roberts hypothesis, the consequent pH drop both initiates ethanol
      fermentation and blocks further production of lactate by inhibiting lactate
      dehydrogenase (LDH). However, the role of LDH in this pH control mechanism is
      still a matter of debate. To perturb the control system in a defined way, a
      barley LDH cDNA under the control of the cauliflower mosaic virus 35S promoter
      was introduced into tomato (Lycopersicon esculentum Mill. cv VFMT) using
      Agrobacterium rhizogenes. The transgenic root clones expressed up to 50 times the
      LDH activity of controls. The fermentative metabolism of these clones was
      compared using roots grown previously in normoxic conditions or roots given a 3-d
      hypoxic pretreatment. During the transition from normoxia to anoxia, lactate
      accumulation was no faster and no more extensive in transgenic roots than in
      controls. Similarly, during prolonged anoxia the flux of 14C from [U-14C] glucose
      to lactate and ethanol was not modified by the expression of the transgene.
      However, in both transgenic and control roots, hypoxic pretreatment increased the
      flux to lactate and promoted lactate export to the medium. These results show
      that LDH has a very low flux control coefficient for lactate fermentation,
      consistent with the Davies-Roberts hypothesis. Moreover, they suggest that
      lactate secretion exerts major control over long-term lactate glycolysis in vivo.

PMID- 12232402
TI  - Choline-O-Sulfate Biosynthesis in Plants (Identification and Partial
      Characterization of a Salinity-Inducible Choline Sulfotransferase from Species of
      Limonium (Plumbaginaceae).
AB  - Choline-O-sulfate is a compatible osmolyte accumulated under saline conditions by
      members of the halophytic genus Limonium and other Plumbaginaceae. A choline
      sulfotransferase (EC 2.8.2.6) responsible for the formation of choline-O-sulfate
      was characterized in Limonium species. A simple radiometric assay was developed
      in which [14C]choline was used as substrate, and the h [14C]choline-O-sulfate
      product was isolated by ion-exchange chromatography. The choline sulfotransferase
      activity was soluble, required 3[prime]-phosphoadenosine-5[prime]-phosphosulfate
      as the sulfate donor, and showed a pH optimum at 9.0. Apparent Km values were 25
      [mu]M for choline and 5.5 [mu]M for 3[prime]-phosphoadenosine-5[prime]
      phosphosulfate. Choline sulfotransferase activity was detected in various
      Limonium species but was very low or absent from species that do not accumulate
      choline-O-sulfate. In roots and leaves of Limonium perezii, the activity was
      increased at least 4-fold by salinization with 40% (v/v) artificial sea water.
      Choline sulfotransferase activity was also induced in cell cultures of L. perezii
      following salt shock with 20% (v/v) artificial sea water or osmotic shock with
      19% (w/v) polyethylene glycol 6000. Labeling experiments with [14C]choline
      confirmed that the enzyme induced in cell cultures was active in vivo.

PMID- 12232403
TI  - Comparison of Dehydrin Gene Expression and Freezing Tolerance in Bromus inermis
      and Secale cereale Grown in Controlled Environments, Hydroponics, and the Field.
AB  - There have been very few reports on the expression of stress-responsive genes in
      field-grown material. A barley dehydrin cDNA was used to investigate the
      expression of dehydrin-like transcripts after low-temperature and abscisic acid
      induced acclimation of bromegrass (Bromus inermis Leyss) suspension cells and of
      bromegrass and rye (Secale cereale) plants grown in the field and under
      controlled environmental conditions. Field-acclimated plants accumulated high
      levels of dehydrin transcripts and were very freezing tolerant. Plants grown in
      pots and hydroponics under controlled environments also accumulated dehydrin
      transcripts and showed increased freezing tolerance. Simulation of a combined
      drought and freezing stress in pots resulted in expression of dehydrin-like
      transcripts comparable to those observed in field-acclimated material.

PMID- 12232404
TI  - Metabolite Signals Regulate Gene Expression and Source/Sink Relations in Cereal
      Seedlings.

PMID- 12232405
TI  - Inhibition of Threonine Dehydratase Is Herbicidal.
AB  - Threonine dehydratase, the first enzyme in isoleucine biosynthesis, catalyzes
      deamination and dehydration of threonine to produce 2-ketobutyrate and ammonia.
      An antimetabolite, 2-(1-cyclohexen-3(R)-yl)-S-glycine (CHG), inhibits the plant
      enzyme. CHG inhibits the growth of Black Mexican Sweet corn (Zea mays) cells and
      of Arabidopsis thaliana plants. The herbicidal effects of CHG can be reversed by
      2-ketobutyrate, other intermediates of isoleucine biosynthesis, and by isoleucine
      itself. These results suggest that the herbicidal effects observed with CHG are a
      consequence of inhibition of threonine dehydratase. The enzyme could be a
      potential target site for an herbicide screening program.

PMID- 12232406
TI  - Expression of the Arabidopsis Gene Akr Coincides with Chloroplast Development.
AB  - Reduced expression of a nuclear gene of Arabidopsis thaliana, Akr, results in the
      formation of chlorotic plants due to a block in the proplastid-to-chloroplast
      development pathway (H. Zhang, D.C. Scheirer, W. Fowle, H.M. Goodman [1992] Plant
      Cell 4: 1575-1588). In an effort to discern the function of the Akr gene product
      in chloroplast development, transgenic plants containing an Akr::[beta]
      glucuronidase gene fusion were constructed to monitor the spatial and temporal
      patterns of Akr expression. Akr is expressed only in chloroplast-containing
      tissues and maximal expression occurs during the seedling stage, coincident with
      chloroplast development. This result is consistent with the hypothesis that Akr
      is required at an early stage of chloroplast development. The effects of an AKR
      deficiency on the expression of nuclear and plastid genes required for
      photosynthetic activity were also examined. Within chloroplast-deficient leaves
      of plants in which Akr expression is limited by the presence of Akr antisense
      transgenes or truncated Akr sense transgenes, mRNAs for the nuclear genes Cab2,
      Cab4, RbcS, and GapA are present at wild-type levels; similarly, levels of mRNAs
      for the plastid genes rbcL and psbA are not affected by the AKR deficiency. Thus,
      although expression of these photosynthetic genes is tightly coordinated with the
      development and maintenance of chloroplasts in wild-type plants, their expression
      is unaffected in AKR-deficient chlorotic leaves. Therefore, we propose that Akr
      functions in a pathway different from the one controlling the expression and
      regulation of the photosynthetic genes during chloroplast development, and at a
      specific developmental stage after the putative plastid factor is made.

PMID- 12232407
TI  - Acquired Resistance in Barley (The Resistance Mechanism Induced by 2,6
      Dichloroisonicotinic Acid Is a Phenocopy of a Genetically Based Mechanism
      Governing Race-Specific Powdery Mildew Resistance).
AB  - Treatment of susceptible barley (Hordeum vulgare) seedlings with 2,6
      dichloroisonicotinic acid (DCINA) induces disease resistance against the powdery
      mildew fungus (Erysiphe graminis f. sp. hordei). A cytological analysis of the
      interaction reveals the hypersensitive cell collapse in attacked, short epidermal
      cells, along with the accumulation of fluorescent material in papillae, that
      appear at the time of fungal arrest. The cell-type-specific hypersensitive
      reaction occurs prior to formation of haustoria, reminiscent of the mechanism
      identified in genetically resistant barley plants containing the functionally
      active Mlg gene (R. Gorg, K. Hollricher, P. Schulze-Lefert [1993] Plant J 3: 857
      866). This observation indicates that the mechanism of DCINA-induced resistance
      is a phenocopy of the mechanism governed by the Mlg locus. The onset of acquired
      resistance correlates with high-level transcript accumulation of barley defense
      related genes encoding pathogenesis-related protein-1, peroxidase, and chitinase
      but not [beta]-1,3-glucanase. Subcellular localization of peroxidase activity
      shows an increase in enzyme activity in the epidermal cell layer and in the
      intercellular fluids of barley leaves. Four out of more than 10 identified
      extracellular isozymes are induced by DCINA. The epidermal cell layer contains a
      major constitutively formed isozyme, together with two isozymes specifically
      induced by DCINA. The data support the hypothesis that host cell death and high
      level accumulation of defense-related gene transcripts are not only commonly
      controlled in certain types of race-specific resistance (A. Freialdenhoven, B.
      Scherag, K. Hollricher, D.B. Collinge, H. Thordal-Christensen, P. Schulze-Lefert
      [1994] Plant Cell 6: 983-994) but also in acquired resistance, which confers
      protection to a broad spectrum of different pathogens.

PMID- 12232408
TI  - The 7[prime]-Methyl Group of Abscisic Acid Is Critical for Biological Activity in
      Wheat Embryo Germination.
AB  - Wheat (Triticum aestivum L.) embryo germination is inhibited by natural (S)-(+)
      abscisic acid (ABA). In this report we have determined critical structural
      features of the ABA molecule, particularly the methyl and ketone groups of the
      ABA ring, required for inhibitory activity. To examine the ring residues a series
      of new optically active ABA analogs have been synthesized in which the 4[prime]
      keto, 7[prime]-, 8[prime]-, or 8[prime]- and 9[prime]-carbons have been replaced
      with hydrogen atoms. Each of the analogs was tested over a range of
      concentrations as a germination inhibitor. Enantiomers of the analogs altered at
      the 4[prime]-keto or 8[prime]- and 9[prime]-methyl groups were active, but less
      so than ABA. Both enantiomers of 7[prime]-demethylABA were inactive as
      germination inhibitors. The results show that the 7[prime]-methyl group is
      absolutely required for activity, but that the other residues are less critical
      for hormone recognition.

PMID- 12232409
TI  - Immunocytochemical Localization of Prunasin Hydrolase and Mandelonitrile Lyase in
      Stems and Leaves of Prunus serotina.
AB  - In macerates of black cherry (Prunus serotina Ehrh.) leaves and stems, (R)
      prunasin is catabolized to HCN, benzaldehyde, and D-glucose by the sequential
      action of prunasin hydrolase (EC 3.2.1.21) and (R)-(+)-mandelonitrile lyase (EC
      4.1.2.10). Immuno-cytochemical techniques have shown that within these organs
      prunasin hydrolase occurs within the vacuoles of phloem parenchyma cells. In
      arborescent leaves, mandelonitrile lyase was also located in phloem parenchyma
      vacuoles, but comparison of serial sections revealed that these two degradative
      enzymes are usually localized within different cells.

PMID- 12232410
TI  - Stimulation of Nitrate and Nitrite Efflux by Ammonium in Barley (Hordeum vulgare
      L.) Seedlings.
AB  - The inhibitory effect of NH4+ on net NO3- uptake has been attributed to an
      enhancement of efflux and, recently, to an inhibition of influx. To study this
      controversy, we devised treatments to distinguish the effects of NH4+ on these
      two processes. Roots of intact barley (Hordeum vulgare L.) seedlings, uninduced
      or induced with NO3- or NO2-, were used. Net uptake and efflux, respectively,
      were determined by following the depletion and accumulation in the external
      solutions. In roots of both uninduced and NO2- -induced seedlings, NO3- efflux
      was negligible; hence, the initial uptake rates were equivalent to influx. Under
      these conditions, NH4+ had little effect on NO3- uptake (influx) rates by either
      the low- or high-Km uptake systems. In contrast, in plants preloaded with NO3-,
      NH4+ and its analog CH3NH3+ decreased net uptake, presumably by enhancing NO3-
      efflux. The stimulatory effect of NH4+ on NO3- efflux was a function of external
      NH4+ and internal NO3- concentration. These results were corroborated by the
      absence of any effect of NH4+ on NO2- uptake unless the roots were preloaded with
      NO2-. In this case NH4+ increased efflux and decreased net uptake. Hence, the
      main effect of NH4+ on net NO3- and NO2- uptake appears to be due to enhancement
      of efflux and not to inhibition of influx.

PMID- 12232411
TI  - Vacuolar-Type H+ -ATPases Are Associated with the Endoplasmic Reticulum and
      Provacuoles of Root Tip Cells.
AB  - To understand the origin of vacuolar H+ -ATPases (V-ATPases) and their cellular
      functions, the subcellular location of V-H+ -ATPases was examined immunologically
      in root cells of oat seedlings. A V-ATPase complex from oat roots consists of a
      large peripheral sector (V1) that includes the 70-kD (A) catalytic and the 60-kD
      (B) regulatory subunits. The soluble V1 complex, thought to be synthesized in the
      cytoplasm, is assembled with the membrane integral sector (V0) at a yet undefined
      location. In mature cells, V-ATPase subunits A and B, detected in immunoblots
      with monoclonal antibodies (Mab) (7A5 and 2E7), were associated mainly with
      vacuolar membranes (20-22% sucrose) fractionated with an isopycnic sucrose
      gradient. However, in immature root tip cells, which lack large vacuoles, most of
      the V-ATPase was localized with the endoplasmic reticulum (ER) at 28 to 31%
      sucrose where a major ER-resident binding protein equilibrated. The peripheral
      subunits were also associated with membranes at 22% sucrose, at 31 to 34% sucrose
      (Golgi), and in plasma membranes at 38% sucrose. Immunogold labeling of root tip
      cells with Mab 2E7 against subunit B showed gold particles decorating the ER as
      well as numerous small vesicles (0.1-0.3 [mu]m diameter), presumably pro
      vacuoles. The immunological detection of the peripheral subunit B on the ER
      supports a model in which the V1 sector is assembled with the V0 on the ER. These
      results support the model in which the central vacuolar membrane originates
      ultimately from the ER. The presence of V-ATPases on several endomembranes
      indicates that this pump could participate in diverse functional roles.

PMID- 12232412
TI  - The rhd6 Mutation of Arabidopsis thaliana Alters Root-Hair Initiation through an
      Auxin- and Ethylene-Associated Process.
AB  - Root-hair initiation in Arabidopsis thaliana provides a model for studying cell
      polarity and its role in plant morphogenesis. Root hairs normally emerge at the
      apical end of root epidermal cells, implying that these cells are polarized. We
      have identified a mutant, rhd6, that displays three defects: (a) a reduction in
      the number of root hairs, (b) an overall basal shift in the site of root-hair
      emergence, and (c) a relatively high frequency of epidermal cells with multiple
      root hairs. These defects implicate the RHD6 gene in root-hair initiation and
      indicate that RHD6 is normally associated with the establishment of, or response
      to, root epidermal cell polarity. Similar alterations in the site of root-hair
      emergence, although less extreme, were also discovered in roots of the auxin-,
      ethylene-, abscisic acid-resistant mutant axr2 and the ethylene-resistant mutant
      etr1. All three rhd6 mutant phenotypes were rescued when either auxin
      (indoleacetic acid) or an ethylene precursor (1-aminocyclopropane-1-carboxylic
      acid) was included in the growth medium. The rhd6 root phenotypes could be
      phenocopied by treating wild-type seedlings with an inhibitor of the ethylene
      pathway (aminoethoxyvinylglycine). These results indicate that RHD6 is normally
      involved in directing the selection or assembly of the root-hair initiation site
      through a process involving auxin and ethylene.

PMID- 12232413
TI  - A Salt-Induced 60-Kilodalton Plasma Membrane Protein Plays a Potential Role in
      the Extreme Halotolerance of the Alga Dunaliella.
AB  - The halotolerant alga Dunaliella salina grows in saline conditions as varied as
      0.5 and 5 M NaCl, maintaining throughout this range a low intracellular ion
      concentration. To discover factors potentially involved in ionic homeostasis, we
      grew cells in media with different salinities or osmolarities and compared their
      protein profiles. The comparisons indicated that the amount of a 60-kD protein,
      p60, greatly increased with an increase in salinity and was moderately enhanced
      when NaCl was substituted with iso-osmotic glycerol. Cells transferred from low
      to high NaCl or from high glycerol to iso-osmotic NaCl media transiently ceased
      to grow, and resumption of growth coincided approximately with an increase in
      p60. The protein, extracted from a plasma membrane fraction, was purified to
      homogeneity. Anti-p60 antibodies cross-reacted with a 60-kD protein in Dunaliella
      bardawil. Immunoelectron microscopy of D. salina cell sections indicated that p60
      was exclusively located in the plasma membrane. Its induction by salt, the
      correlation between its accumulation and growth resumption in high concentrations
      of salt, and its plasma membrane localization suggest the possibility that p60
      could play a role in ionic homeostasis in conditions of high salinity, although
      different types of function could also be considered.

PMID- 12232414
TI  - The Metabolism of Gibberellin A20 to Gibberellin A1 by Tall and Dwarf Mutants of
      Oryza sativa and Arabidopsis thaliana.
AB  - The purpose of this study was to demonstrate the metabolism of gibberellin A20
      (GA20) to gibberellin A1 (GA1) by tall and mutant shoots of rice (Oryza sativa
      L.) and Arabidopsis thaliana (L.) Heynh. The data show that the tall and dx
      mutant of rice and the tall and ga5 mutant of Arabidopsis metabolize GA20 to GA1.
      The data also show that the dy mutant of rice and the ga4 mutant of Arabidopsis
      block the metabolism of GA20 to GA1. [17-13C,3H]GA20 was fed to tall and the
      dwarf mutants, dx and dy, of rice and tall and the dwarf mutants, ga5 and ga4, of
      Arabidopsis. The metabolites were analyzed by high-performance liquid
      chromatography and full-scan gas chromatography-mass spectrometry together with
      Kovats retention index data. For rice, the metabolite [13C]GA, was identified
      from tall and dx seedlings; [13C]GA1 was not identified from the dy seedlings.
      [13C]GA29 was identified from tall, dx, and dy seedlings. For Arabidopsis, the
      metabolite [13C]GA1 was identified from tall, ga5, and ga4 plants. The amount of
      [13C]GA1 from ga4 plants was less than 15% of that obtained from tall and ga5
      plants. [13C]GA29 was identified from tall, ga5, and ga4 plants. [13C]GA5 and
      [13C]GA3 were not identified from any of the six types of plant material.

PMID- 12232415
TI  - The 58-Kilodalton Calmodulin-Binding Glutamate Decarboxylase Is a Ubiquitous
      Protein in Petunia Organs and Its Expression Is Developmentally Regulated.
AB  - A cDNA coding for a 58-kD calcium-dependent calmodulin (CaM)-binding glutamate
      decarboxylase (GAD) previously isolated in our laboratory from petunia (Petunia
      hybrida) (G. Baum, Y. Chen, T. Arazi, H. Takatsuji, H. Fromm [1993] J Biol Chem
      268: 19610-19617) was used to conduct molecular studies of GAD expression. GAD
      expression was studied during petunia organ development using the GAD cDNA as a
      probe to detect the GAD mRNA and by the anti-recombinant GAD serum to monitor the
      levels of GAD. GAD activity was studied in extracts of organs in the course of
      development. The 58-kD CaM-binding GAD is expressed in all petunia organs tested
      (flowers and all floral parts, leaves, stems, roots, and seeds). The highest
      expression levels were in petals of open flowers. Developmental changes in the
      abundance of GAD mRNA and the 58-kD GAD were observed in flowers and leaves and
      during germination. Moreover, developmental changes in GAD activity in plant
      extracts coincided in most cases with changes in the abundance of the 58-kD GAD.
      We conclude that the 58-kD CaM-binding GAD is a ubiquitous protein in petunia
      organs and that its expression is developmentally regulated by transcriptional
      and/or posttranscriptional processes. Thus, GAD gene expression is likely to play
      a role in controlling the rates of GABA synthesis during petunia seed germination
      and organ development.

PMID- 12232416
TI  - Genotypes of the Common Bean (Phaseolus vulgaris L.) Lacking the Nodule-Enhanced
      Isoform of Glutamine Synthetase.
AB  - Glutamine synthetase (GS) is an octameric enzyme. The nodule cytosol of the
      common bean (Phaseolus vulgaris L.) has two major types of GS subunit
      polypeptides ([beta] and [gamma]). As a result, nine different isozymes
      containing varied proportions of [beta] and [gamma] can be generated. The
      isozymes are resolvable by native polyacrylamide gel electrophoresis. Staining
      the gel for GS activity reveals two isoforms, GSn1, which is nodule enhanced and
      is composed of the eight [gamma] polypeptide-containing isozymes, and GSn2, which
      is the isozyme [beta]8. We screened 104 cultivars and genotypes of common beans
      for variations in isozyme formation and found two, PI317350 and PI326054, that
      had no GSn1. The PI beans appeared to nodulate normally and had cytosolic protein
      concentrations and total GS activities similar to those of the cultivar UI-111,
      which has GSn1. They accumulated the [gamma] polypeptide, which had the same
      molecular weight (46,000) and isoelectric point (6.3) as the [gamma] polypeptide
      of UI-111. Experiments with extracts prepared by mixing UI-111 and the PI bean
      nodules suggested that the PI bean nodule extracts did not have an inhibitor or a
      proteolytic system that specifically inhibited or degraded GSn1. Nodules from UI
      111 and the PI beans were dissected into cortex and central infection zone tissue
      fractions. GSn2 was found in the cortex and the central infection zone tissue of
      all beans. Our results suggested that the reason we were unable to detect GSn1
      from the PI beans was not because their GSn1 and GSn2 had an identical
      electrophoretic mobility, nor was it due to an inhibited or unstable GSn1. Our
      results suggested that either their [gamma] gene had mutated in the region that
      is essential for the [gamma] polypeptide to assemble or the assembly of GS may
      require a chaperone. In the two PI beans, the chaperone accumulated to a lower
      level than it did in UI-111. This lower amount limited the assembly of the
      [gamma] polypeptide into GS.

PMID- 12232417
TI  - Expression of Sporophytic Storage Proteins in the Corm of the Quillwort (Isoetes
      echinospora Dur.).
AB  - Parenchyma cells from the corm tissue of the aquatic lycopod Isoetes echinospora
      Dur. were shown by electron microscopy to be packed with amyloplasts, lipid
      bodies, and protein bodies. The protein bodies are morphologically similar to
      those identified in seeds and certain vegetative tissues of higher plants.
      Globoid-containing protein bodies (1-10 [mu]m) isolated in a sucrose gradient
      possessed a buoyant density of 1.28 g/mL and contained globulin (salt-soluble)
      proteins. Sucrose gradient centrifugation of crude globulins revealed only two
      components with mean sedimentation coefficients of approximately 2S and 11S. The
      2S component, designated VSP-IsA, was composed of a 15.7-kD polypeptide. The 11S
      component, designated VSP-IsB, had a molecular mass of 215 kD as estimated by gel
      filtration and was composed of 39- to 42-kD polypeptides. Two-dimensional gel
      electrophoresis showed constituent polypeptides distinguished by differences in
      net charge and molecular mass. Affinity-purified antibodies against VSP-IsA and
      VSP-IsB prepared and used as probes on immunoblots cross-react only with their
      specific antigens, suggesting that the proteins are not immunologically related.
      Indirect immunolocalization studies confirmed that VSP-IsB is deposited in
      protein bodies. These globulin proteins, like those from some seeds, form the
      principal storage reserves of the corm tissue.

PMID- 12232418
TI  - Identification of Posttranslationally Modified 18-Kilodalton Protein from Rice as
      Eukaryotic Translation Initiation Factor 5A.
AB  - Using anther-derived rice (Oryza sativa L.) cell-suspension cultures, we have
      identified an 18-kD protein that is posttranslationally modified by spermidine
      and is influenced by endogenous polyamine levels. The posttranslationally
      modified residue has been identified as the unusual amino acid hypusine
      [N[epsilon]-(4-amino-2-hydroxybutyl)lysine] by reverse-phase high-performance
      liquid chromatography and gas chromatography-mass-spectrometry analyses.
      Differential labeling of the protein with labeled amines provided evidence that
      the butylamine moiety of spermidine is the immediate precursor of the hypusine
      residue in the protein. The eukaryotic translation initiation factor 5A (eIF-5A)
      is the only known mammalian protein that undergoes a similar posttranslational
      modification with hypusine. The purified 18-kD protein co-electrophoreses with
      human translational initiation factor eIF-5A in both isoelectric focusing and
      sodium dodecyl sulfate-polyacrylamide gels. The purified protein from rice
      stimulated methionyl-puromycin synthesis in vitro, indicating its functional
      similarity to mammalian eIF-5A. The results presented provide evidence that the
      posttranslationally modified 18-kD protein from rice containing hypusine is eIF
      5A and suggest the conservation of hypusine-containing translation initiation
      factor eIF-5A in eukaryotes.

PMID- 12232419
TI  - Regulation of Alternative Oxidase Activity by Pyruvate in Soybean Mitochondria.
AB  - The regulation of alternative oxidase activity by the effector pyruvate was
      investigated in soybean (Glycine max L.) mitochondria using developmental changes
      in roots and cotyledons to vary the respiratory capacity of the mitochondria.
      Rates of cyanide-insensitive oxygen uptake by soybean root mitochondria declined
      with seedling age. Immunologically detectable protein levels increased slightly
      with age, and mitochondria from younger, more active roots had less of the
      protein in the reduced form. Addition of pyruvate stimulated cyanide-insensitive
      respiration in root mitochondria, up to the same rate, regardless of seedling
      age. This stimulation was reversed rapidly upon removal of pyruvate, either by
      pelleting mitochondria (with succinate as substrate) or by adding lactate
      dehydrogenase with NADH as substrate. In mitochondria from cotyledons of the same
      seedlings, cyanide-insensitive NADH oxidation was less dependent on added
      pyruvate, partly due to intramitochondrial generation of pyruvate from endogenous
      substrates. Cyanide-insensitive oxygen uptake with succinate as substrate was
      greater than that with NADH, in both root and cotyledon mitochondria, but this
      difference became much less when an increase in external pH was used to inhibit
      intramitochondrial pyruvate production via malic enzyme. Malic enzyme activity in
      root mitochondria declined with seedling age. The results indicate that the
      activity of the alternative oxidase in soybean mitochondria is very dependent on
      the presence of pyruvate: differences in the generation of intramitochondrial
      pyruvate can explain differences in alternative oxidase activity between tissues
      and substrates, and some of the changes that occur during seedling development.

PMID- 12232420
TI  - Inhibition of Barnyardgrass 4-Hydroxyphenylpyruvate Dioxygenase by Sulcotrione.
AB  - 4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27) was partially purified from
      barnyardgrass (Echinochloa crus-galli L.) leaves and assayed by high-performance
      liquid chromatography analysis of product formation or by the capture of released
      14CO2. The bleaching herbicide sulcotrione [2-(2-chloro-4-methanesulfonylbenzoyl)
      1,3-cyclohexanedione] was shown to be a potent, linear competitive inhibitor of 4
      hydroxyphenylpyruvate dioxygenase. Kinetic analyses determined that the Km for
      the substrate, 4-hydroxyphenylpyruvate, was 4.3 [mu]M, and the Ki value was 9.8
      nM for sulcotrione.

PMID- 12232421
TI  - A Mutant of Arabidopsis with Increased Levels of Stearic Acid.
AB  - A mutation at the fab2 locus of Arabidopsis caused increased levels of stearate
      in leaves. The increase in leaf stearate in fab2 varied developmentally, and the
      largest increase occurred in young leaves, where stearate accounted for almost
      20% of total leaf fatty acids. The fatty acid composition of leaf lipids isolated
      from the fab2 mutant showed increased stearate in all the major glycerolipids of
      both the chloroplast and extrachloroplast membranes. Although the stearate
      content was increased, the fab2 mutant still contained abundant amounts of 18:1,
      18:2, and 18:3 fatty acids. These results are consistent with the expectations
      for a mutation partially affecting the action of the stromal stearoyl-acyl
      carrier protein desaturase. Positional analysis indicated that the extra 18:0 is
      excluded with high specificity from the sn-2 position of both chloroplast and
      extrachloroplast glycerolipids. Although stearate content was increased in all
      the major leaf membrane lipids, the amount of increase varied considerably among
      the different lipids, from a high of 25% of fatty acids in phosphatidylcholine to
      a low of 2.9% of fatty acids in monogalactosyldiacylglycerol.

PMID- 12232422
TI  - Tomato Fruit Polygalacturonase Isozyme 1 (Characterization of the [beta] Subunit
      and Its State of Assembly in Vivo).
AB  - Polygalacturonase isozyme 1 (PG1) is a heterodimer comprising a catalytic and
      noncatalytic or [beta] subunit, whereas polygalacturonase isozyme 2 (PG2)
      comprises only the catalytic subunit. To assess the state of assembly of PG1 in
      vivo, both subunits were purified to homogeneity and used to study assembly of
      the heterodimer. PG1 could be reconstituted in vitro from purified [beta] subunit
      and purified PG2 under a wide range of salt and pH conditions, and PG1
      reconstituted in vitro was indistinguishable from PG1 isolated from tomato
      (Lycopersicon esculentum) fruit. Specific antibodies indicated that the [beta]
      subunit was present in fruit of all developmental stages, but absent in
      vegetative tissue. The state of assembly of PG1 in vivo was tested based on the
      differential thermal stability of PG1 and PG2 by heating segments of ripe fruit
      pericarp tissue. Temperatures well below those required to inactivate PG1 in
      vitro caused the loss of activity of both PG1 and PG2, suggesting that only heat
      labile PG2 is present in vivo. In addition, when extracts of ripe fruit were
      rigorously maintained and analyzed at 4[deg]C, PG1 was absent or barely
      detectable. These results are consistent with the hypothesis that PG1 can
      assemble spontaneously and is essentially absent in intact tomato fruit but forms
      artifactually from PG2 and the [beta] subunit during the extraction of tomato
      fruit tissue when low temperatures are not rigorously maintained.

PMID- 12232423
TI  - Effects of 3,5-Dibromo-4-Hydroxybenzonitrile (Bromoxynil) on Bioenergetics of
      Higher Plant Mitochondria (Pisum sativum).
AB  - The herbicide bromoxynil (3,5-dibromo-4-hydroxybenzonitrile) was tested on
      mitochondria from etiolated pea (Pisum sativum L. cv Alaska) stems. This compound
      when used at micromolar concentrations ([almost equal to]20 [mu]M) inhibited
      malate- and succinate-dependent respiration by intact mitochondria but not
      oxidation of exogenously added NADH. Bromoxynil did not affect the activities of
      the succinic and the internal NADH dehydrogenases. Analyses of the effects
      induced by this herbicide on the membrane potential, [delta]pH, matrix Ca2+
      movements, and dicarboxylate transport demonstrated that bromoxynil is likely to
      act as an inhibitor of the dicarboxylate carrier. In addition, bromoxynil caused
      a mild membrane uncoupling at concentrations [greater than or equal to]20 [mu]M.
      No effect on the ATPase activity was observed.

PMID- 12232424
TI  - Molecular Genetic Alteration of Plant Respiration (Silencing and Overexpression
      of Alternative Oxidase in Transgenic Tobacco).
AB  - The alternative oxidase (AOX) of plant mitochondria is encoded by the nuclear
      gene Aox1. Sense and antisense DNA constructs of Nicotiana tabacum Aox1 were
      introduced into tobacco, and transgenic plants with both increased and decreased
      levels of mitochondrial AOX protein were identified. Suspension cells derived
      from wild-type and transgenic plants were grown in heterotrophic batch culture.
      Transgenic cells with increased AOX protein had an increased capacity for cyanide
      resistant, salicylhydroxamic acid-sensitive respiration compared to wild-type
      cells, whereas transgenic cells with decreased AOX protein had a decreased
      capacity for such respiration. Thus, genetic alteration of the level of AOX
      protein was sufficient to alter the capacity for electron transport through the
      alternative pathway. Under our standard growth conditions, "antisense" cells with
      dramatically reduced levels of AOX protein had growth and respiration rates
      similar to the wild type. However, whereas wild-type cells were able to grow
      under conditions that severely suppressed cytochrome pathway activity, antisense
      cells could not survive this treatment. This suggests that a critical function of
      AOX may be to support respiration when the cytochrome pathway is impaired. The
      much higher level of AOX protein in "sense" cells compared to the wild type did
      not appreciably alter the steady-state partitioning of electrons between the
      cytochrome path and the alternative pathway in vivo, suggesting that this
      partitioning may be subject to additional regulatory factors.

PMID- 12232425
TI  - A Novel Metabolic Pathway for Indole-3-Acetic Acid in Apical Shoots of Populus
      tremula (L.) x Populus tremuloides (Michx.).
AB  - Metabolism of indole-3-acetic acid (IAA) in apical shoots of Populus tremula (L.)
      x Populus tremuloides (Michx.) was investigated by feeding a mixture of [12C]IAA,
      [13C6]IAA, and [1[prime]-14C]IAA through the base of the excised stem. HPLC of
      methanolic plant extracts revealed eight major radiolabeled metabolites after a
      24-h incubation period. Comparison between feeds with [5-3H]IAA and [1[prime]
      14C]IAA showed that all detectable metabolites were nondecarboxylative products.
      The purified radiolabeled HPLC fractions were screened by frit-fast atom
      bombardment liquid chromatography-mass spectrometry for compounds with
      characteristic fragment pairs originating from the application with 12C and 13C
      isotopes. Samples of interest were further characterized by gas chromatography
      mass spectrometry. Using this procedure, oxindole-3-acetic acid (OxIAA), indole-3
      acetyl-N-aspartic acid (IAAsp), oxindole-3-acetyl-N-aspartic acid (OxIAAsp), and
      ring-hydroxylated oxindole-3-acetic acid were all identified as IAA metabolites.
      Furthermore, a novel metabolic pathway from IAA via IAAsp and OxIAAsp to OxIAA
      was established on the basis of refeeding experiments with the different IAA
      metabolites.

PMID- 12232426
TI  - Control of Internode Length in Pisum sativum (Further Evidence for the
      Involvement of Indole-3-Acetic Acid).
AB  - The effects of altered endogenous indole-3-acetic (IAA) levels on elongation in
      garden pea (Pisum sativum L.) plants were investigated. The auxin transport
      inhibitors 2,3,5-triiodobenzoic acid (TIBA) and 9-hydroxyfluorene-9-carboxylic
      acid (HFCA) were applied to elongating internodes of wild-type and mutant lkb
      plants. The lkb mutant was included because elongating lkb internodes contained 2
      to 3-fold less free IAA than those of the wild type. In the wild type, TIBA
      reduced both the IAA level and internode elongation below the site of
      application. Both TIBA and HFCA strongly promoted the elongation of lkb
      internodes and also raised IAA levels above the application site. The synthetic
      auxin 2,4-dichlorophenoxyacetic acid (2,4-D) also markedly increased internode
      elongation in lkb plants and virtually restored petioles and tendrils to their
      wild-type length. In contrast, treatment of wild-type plants with TIBA, HFCA, or
      2,4-D caused little or no increase in elongation above the application site. The
      ethylene synthesis inhibitor aminoethoxyvinylglycine also increased stem
      elongation in lkb plants, and combined application of HFCA and aminoethoxy
      vinylglycine restored lkb internodes to the wild-type length. It is concluded
      that the level of IAA in wild-type internodes is necessary for normal elongation,
      and that the reduced stature of lkb plants is at least partially attributable to
      a reduction in free IAA level in this mutant.

PMID- 12232427
TI  - Biosynthesis of Cardiolipin in Plant Mitochondria.
AB  - The properties of cardiolipin synthase were investigated in mitochondria and
      submitochondrial fractions from etiolated mung bean (Vigna radiata L.) seedlings.
      Direct evidence is presented that the enzyme utilizes CDP-diacylglycerol in
      addition to phosphatidylglycerol for the synthesis of cardiolipin. Cardiolipin
      synthase had an alkaline pH optimum of about 9 and required divalent cations for
      activity. Maximal activity was obtained in the presence of 16 mM MnCl2. The
      apparent Km values for CDP-diacylglycerol and phosphatidylglycerol were 0.8 and
      50 [mu]M, respectively. Cardiolipin synthase was localized predominantly in the
      inner membrane of mung bean mitochondria and displayed a substrate species
      specificity. Highest activities were measured with the dioleoyl species of both
      CDP-diacylglycerol and phosphatidylglycerol, and somewhat lower activities were
      measured with mixed species of the two substrates containing a palmitoyl and an
      oleoyl group. On the other hand, the cardiolipin synthase hardly used the
      dipalmitoyl species and strongly discriminated against CDP-dipalmitoylglycerol
      from a mixture with CDP-dioleoylglycerol.

PMID- 12232428
TI  - Floral Scent Production in Clarkia (Onagraceae) (I. Localization and
      Developmental Modulation of Monoterpene Emission and Linalool Synthase Activity).
AB  - The flowers of many plants emit volatile compounds as a means of attracting
      pollinators. We have previously shown that the strong, sweet fragrance of Clarkia
      breweri (Onagraceae), an annual plant native to California, consists of
      approximately 8 to 12 volatile compounds[mdash]three monoterpenes and nine
      benzoate derivatives (R.A. Raguso and E. Pichersky [1994] Plant Syst Evol [in
      press]). Here we report that the monoterpene alcohol linalool is synthesized and
      emitted mostly by petals but to a lesser extent also by the pistil and stamens.
      Two linalool oxides are produced and emitted almost exclusively by the pistil.
      These three monoterpenes are first discernible in mature unopened buds, and their
      tissue levels are highest during the first 2 to 3 d after anthesis. Levels of
      emission by the different floral parts throughout the life span of the flower
      were correlated with levels of these monoterpenes in the respective tissues,
      suggesting that these monoterpenes are emitted soon after their synthesis.
      Activity of linalool synthase, an enzyme that converts the ubiquitous C10
      isoprenoid intermediate geranyl pyrophosphate to linalool, was highest in petals,
      the organ that emits most of the linalool. However, linalool synthase activity on
      a fresh weight basis was highest in stigma and style (i.e. the pistil). Most of
      the linalool produced in the pistil is apparently converted into linalool oxides.
      Lower levels (0.1%) of monoterpene emission and linalool synthase activity are
      found in the stigma of Clarkia concinna, a nonscented relative of C. breweri,
      suggesting that monoterpenes may have other functions in the flower in addition
      to attracting pollinators.

PMID- 12232429
TI  - Immediate Activation of Respiration in Petroselinum crispum L. in Response to the
      Phytophthora megasperma f. sp. Glycinea Elicitor.
AB  - Treatment of parsley (Petroselinum crispum L.) cell cultures with the
      Phytophthora megasperma elicitor isolated from the fungus Phytophthora megasperma
      f. sp. Glycinea caused an immediate increase in the rate of respiratory CO2
      evolution in the dark. The respiratory response was biphasic, showing a rapid
      enhancement in the first 20 min and then a slower increase until a steady rate
      was attained 60 min posttreatment. The enhanced rate of CO2 evolution
      corresponded to the activation of phosphofructokinase and glucose-6-phosphate
      dehydrogenase, key enzymes in the regulation of carbohydrate flow to glycolysis
      and the oxidative pentose phosphate (OPP) pathway, respectively. The increased
      rate of CO2 evolution and the activation of phosphofructokinase and glucose-6
      phosphate dehydrogenase were maintained for the duration of the experiments,
      indicating long-term stimulation of respiration through both glycolysis and the
      OPP pathway. A 23% decrease in the C6:C1 ratio of 14CO2 evolution from labeled
      glucose 60 min after the addition of Phytophthora megasperma elicitor is
      consistent with an increased contribution of the OPP pathway to cellular
      respiration. Long-term activation of the OPP pathway following elicitation could
      serve to maintain the pools of substrates necessary during activation of the
      shikimic acid pathway, leading to the production of defensive compounds.

PMID- 12232430
TI  - Release of Photosynthetic Protein Catabolites by Blebbing from Thylakoids.
AB  - Thylakoid proteins and their catabolites have been detected in lipid-protein
      particles isolated from the stroma of intact chloroplasts obtained from primary
      leaves of 2-week-old bean seedlings (Phaseolus vulgaris L. cv Kinghorn). The
      lipid-protein particles bear morphological resemblance to plastoglobuli seen in
      the chloroplasts of senescing leaves, but they are much smaller. They range from
      10 to 320 nm in radius, are uniformly stained in thin sections visualized by
      transmission electron microscopy, and are discernible in the stroma of
      chloroplasts in corresponding thin-sectioned leaf tissue. The lipid-protein
      particles contain thylakoid lipids and are enriched in free fatty acids.
      Specifically, the free-to-esterified fatty acid ratio is about 1:1 in the
      particles compared to only 1:18 for corresponding thylakoid membranes. Western
      blot analyses indicate that these particles also contain thylakoid proteins and,
      in some cases, catabolites of these proteins including the CF1 [beta] and [gamma]
      subunits of ATPase, cytochrome f, and the 31- and 33-kD proteins of PSII. Lipid
      protein particles with similar properties were generated in vitro from isolated,
      light-stressed thylakoids. Collectively, these data suggest that blebbing of
      lipid-protein particles may be a means of removing potentially destabilizing
      macromolecular catabolites from thylakoid membrane bilayers.

PMID- 12232431
TI  - Modifications of Etioplasts in Cotyledons during Prolonged Dark Growth of Sugar
      Beet Seedlings (Identification of Etiolation-Related Plastidial Aminopeptidase
      Activities).
AB  - We studied the effects of prolonged dark growth on proplastids and etioplasts in
      cotyledons of sugar beet (Beta vulgaris L.) seedlings. Differentiation of
      proplastids into etioplasts occurred between d 4 and d 6 after imbibition, with
      the typical characteristics of increased synthesis of plastidial proteins,
      protein and carotenoid accumulation, size increase, development of plastid
      membranes and of the prolamellar body, and increase of the greening capacity.
      However, this situation of efficient greening capacity was short-lived. The
      greening capacity started to decline from d 6 after imbibition. This decline was
      due in part to reserve depletion and glucose limitation and also to irreversible
      damage to plastids. Indeed, electron microscopy observations in situ showed some
      signs of plastidial damage, such as accumulation of plastoglobuli and membrane
      alterations. The biochemical characterization of purified plastids also showed a
      decrease of proteins per plastid. Aminopeptidase activities, and to a lesser
      extent, neutral endopeptidase activities, were found to increase in plastids
      during this degenerative process. We identified two plastidial aminopeptidases
      showing a sharp increase of activity at the onset of the degenerative process.
      One of them, an alanyl aminopeptidase, was shown to be inactivated by exposure to
      light or addition of exogenous glucose, thus confirming the relationship with
      prolonged dark growth and indicating a relationship with glucose limitation.

PMID- 12232432
TI  - Control of Paraheliotropism in Two Phaseolus Species.
AB  - Paraheliotropic (light-avoiding) leaf movements have been associated with high
      light intensity, high temperature, and drought. We investigated leaf elevation
      for intact plants, pulvinus bending for excised motor organs, and size change for
      protoplasts from motor tissue for two Phaseolus species: Phaseolus acutifolius A.
      Gray, native to hot, arid regions, and Phaseolus vulgaris L., the common bean.
      Leaf angles above horizontal were measured for central trifoliolate leaflets of
      intact plants at 24, 27, and 30[deg]C at 500 and 750 [mu]mol photons (400-700 nm)
      m-2 s-1 over a range of water potentials; equivalent angles were determined for
      excised motor organs under similar conditions. Diameters were measured for
      protoplasts from abaxial and adaxial motor tissue over a range of photon flux
      density values, temperatures, and water potentials. In general, higher photon
      flux density and temperature resulted in elevation of leaves, bending of excised
      pulvini, and equivalent changes in protoplast volume (swelling of abaxial
      protoplasts and shrinking of adaxial protoplasts). In intact plants, lower water
      potentials yielded greater paraheliotropism; abaxial protoplasts increased in
      size, whereas adaxial ones did not change. P. acutifolius typically exhibited
      greater paraheliotropism than did P. vulgaris under the same conditions, a set of
      physiological responses likely to be highly adaptive in its native arid habitat.

PMID- 12232433
TI  - Use of a Gouy-Chapman-Stern Model for Membrane-Surface Electrical Potential to
      Interpret Some Features of Mineral Rhizotoxicity.
AB  - A consideration of mineral toxicity to roots only in terms of ion activities in
      the rooting medium can be misleading. A Gouy-Chapman-Stern model, by which
      relative ion activities at cell-membrane surfaces may be estimated, has been
      applied to problems of mineral rhizotoxicity, including the toxicity of Al3+,
      La3+, H+, Na+, and SeO42-, to wheat (Triticum aestivum L.) roots. The Gouy
      Chapman portion of the model is expressed in the Grahame equation, which relates
      the charge density ([sigma]) and electrical potential (E0) at the surface of a
      membrane to the concentrations of ions in a contracting bulk solution. The Stern
      modification of the theory takes into account changes in [sigma] caused by ion
      binding at the membrane surface. Several theoretical problems with the model and
      its use are considered, including the fact that previous authors have usually
      related the physiological effects of an ion at a membrane surface to the computed
      concentration (Ci0) of the unbound ion rather than its computed activity (ai0).
      This practice implies the false assumption that Ci0 is proportional to ai0. It is
      demonstrated here that ai0, computed from external activities (ai[infinity
      symbol]) by a Nernst equation [ai0 = ai[infinity symbol]exp([mdash]ZiFE0/RT),
      where Zi is the charge on the ion, F is the Faraday constant, R is the gas
      constant, and T is the temperature], correlates well with ion toxicity and that
      Ci0 sometimes correlates poorly. These conclusions also apply to issues of
      mineral nutrition.

PMID- 12232434
TI  - Expression of the Enzymes of Nitrate Reduction during the Anaerobic Germination
      of Rice.
AB  - During the anaerobic germination of rice (Oryza sativa L.), nitrate is
      translocated from the caryopsis and assimilated into the coleoptile (R. Reggiani,
      M. Mattana, N. Aurisano, A. Bertani [1993] Plant Cell Physiol 34: 379-383). Using
      antibodies against nitrate and nitrite reductases, proteins with the expected
      molecular mass were recognized by western blot analysis in extracts from 8-d-old
      rice coleoptiles. Both enzymes are de novo synthesized in 6- to 8-d-old
      seedlings, as shown by immunoprecipitation of radiolabeled proteins from young
      plants grown in the presence of [35S]methio-nine. The anaerobic synthesis of both
      enzymes was enhanced by the addition of 5 mM KNO3. The effect of exogenous
      nitrate on the expression of the corresponding genes in anaerobic rice
      coleoptiles was revealed by the analysis of their transcripts. The importance of
      the expression of these enzymes during the anaerobic development of rice
      seedlings is discussed.

PMID- 12232435
TI  - A Mutation at the fad8 Locus of Arabidopsis Identifies a Second Chloroplast
      [omega]-3 Desaturase.
AB  - Two independently isolated mutations at the fad7 locus in Arabidopsis produced
      plants with a temperature-conditional phenotype. Leaves of fad7 mutants grown at
      28[deg]C contained less than 30% of wild-type levels of trienoic fatty acids
      (16:3 plus 18:3) compared with more than 70% of wild-type levels for plants grown
      at 15[deg]C. Screening of an M2 population derived from the fad7-1 line led to
      the identification of a line, SH1, in which the proportion of trienoic acids was
      much less than in fad7 plants. The segregation pattern of F2 progeny from a cross
      between SH1 and wild type indicated that the additional fatty acid mutation in
      SH1 is at a new locus, designated fad8. In a genetic background that was wild
      type at the FAD7 locus, the fad8 mutation had no detectable effect on overall
      leaf fatty acid composition irrespective of the temperature at which plants were
      grown. However, fatty acid analyses of individual leaf lipids revealed small
      decreases in the levels of 18:3 in two chloroplast lipids. In fad8 plants grown
      at 22[deg]C, phospha-tidylglycerol contained 22.5% 18:3 compared with 33.5% in
      wild-type Arabidopsis. For sulfoquinovosyldiacylglycerol, the values were 31.4
      and 44.5%, respectively. Together with information from studies of the cloned
      FAD8 gene (S. Gibson, V. Arondel, K. Iba, C. Somerville [1994] Plant Physiol 106:
      1615-1621), these results indicate that the FAD8 locus encodes a chloroplast
      localized 16:2/18:2 desaturase that has a substrate specificity similar to the
      FAD7 gene product but that is induced by low temperature.

PMID- 12232436
TI  - Fourier-Transform Raman and Fourier-Transform Infrared Spectroscopy (An
      Investigation of Five Higher Plant Cell Walls and Their Components).
AB  - Infrared and Raman spectra of sequentially extracted primary cell walls and their
      pectic polymers were obtained from five angiosperm plants. Fourier-transform
      Raman spectrometry was shown to be a powerful tool for the investigation of
      primary cell-wall architecture at a molecular level, providing complementary
      information to that obtained by Fourier-transform infrared microspectroscopy. The
      use of an extraction procedure using imidazole instead of cyclohexane trans-1,2
      N,N,N[prime],N[prime]-diaminotetraacetate allows the extension of the infrared
      spectral window for data interpretation from 1300 to 800 cm-1, to 2000 to 800 cm
      1, and allows us to obtain Raman spectra from extracted cell-wall material. Wall
      constituents such as pectins, proteins, aromatic phenolics, cellulose, and
      hemicellulose have characteristic spectral features that can be used to identify
      and/or fingerprint these polymers without, in most cases, the need for any
      physical separation. The Gramineae (rice [Oryza sativa], polypogon [Polypogon
      fugax steud], and sweet corn [Zea mays]) are spectroscopically very different
      from the nongraminaceous monocotyledon (onion [Allium cepa]) and the dicotyledon
      (carrot [Daucus carota]); this reflects differences in chemical composition and
      cross-linking of the walls. The possibility of a taxonomic classification of
      plant cell walls based on infrared and Raman spectroscopies and the use of
      spectral fingerprinting for authentication and detection of adulteration of
      products rich in cell-wall materials are discussed.

PMID- 12232437
TI  - Distribution of Pyruvate Dehydrogenase Complex Activities between Chloroplasts
      and Mitochondria from Leaves of Different Species.
AB  - Protoplasts from barley (Hordeum vulgare), pea (Pisum sativum), wheat (Triticum
      aestivum), and spinach (Spinacia oleracea) leaves were fractionated into
      chloroplast- and mitochondrion-enriched fractions. Pyruvate dehydrogenase complex
      capacities in mitochondria (mtPDC) and chloroplasts (cpPDC) were measured in
      appropriate fractions under conditions optimal for each isozyme. The total
      cellular capacity of PDC was similar in barley and pea but about 50% lower in
      wheat and spinach. In pea a distribution of 87% mtPDC and 13% cpPDC was found on
      a cellular basis. In barley, wheat, and spinach the subcellular distribution was
      the opposite, with about 15% mtPDC and 85% cpPDC. cpPDC activity was constant at
      about 0.1 nmol cell-1 h-1 in cells from different regions along the developing
      barley leaf and showed no correlation with developmental patterns of
      photosynthetic parameters, such as increasing Chl and NADP-glyceraldehyde-3
      phosphate dehydrogenase activity. Similarly, the capacity of the mitochondrial
      isoform did not change during barley leaf development and had a developmental
      pattern similar to that of citrate synthase and fumarase. Differences in
      subcellular distribution of PDCs in barley and pea are proposed to be due to
      differences in regulation, not to changes in isozyme proportions during leaf
      development or to species-specific differences in phosphorylation state of mtPDC
      after organelle separation.

PMID- 12232438
TI  - Collapse of Water-Stress Emboli in the Tracheids of Thuja occidentalis L.
AB  - We report the kinetics of embolus formation and collapse in the tracheids of
      Thuja occidentalis L. stem segments. Radial wood sections were trimmed to 4 mm
      long paralleling the tracheids by 1 mm wide and 0.1 mm thick. They were observed
      under a dissecting microscope at 128x while sections were dehydrated and
      rehydrated. During dehydration, cavitations resulted in the formation of emboli
      in tracheids, but we concluded that the cavitated tracheids did not immediately
      fill with air at atmospheric pressure. This conclusion was based on the time
      required for the emboli to collapse after the rewetting of the dehydrated
      segment. By hypothesis, the time for the emboli to collapse should be
      proportional to the amount of air in the emboli. The time for all the emboli to
      collapse was a linear function of the dehydration time for times up to 15 min.
      For dehydrations greater than 80 min, the time for collapse after rewetting was
      constant, and we concluded that the tracheids have saturated with air by 80 min
      of dehydration. The kinetics of embolus formation is discussed in terms of the
      air-seeding hypothesis for cavitation, and collapse is discussed in terms of the
      physics of gas dissolution and diffusion. Embolus formation and dissolution in
      intact herbaceous and woody plants should follow the same physical laws.

PMID- 12232439
TI  - Intrathylakoid pH in Isolated Pea Chloroplasts as Probed by Violaxanthin
      Deepoxidation.
AB  - Light-driven violaxanthin deepoxidation was measured in isolated pea (Pisum
      sativum) chloroplasts without ATP synthesis (basal conditions) and with ATP
      synthesis (coupled conditions). Thylakoids stored in high salt (HS) or low salt
      (LS) storage medium were tested. In previous experiments, HS thylakoids and LS
      thylakoids were related to delocalized and localized proton coupling,
      respectively.Light-driven deepoxidase activity was compared to the pH dependence
      of deepoxidase activity established in dark reactions. At an external pH of 8,
      light-driven deepoxidation indicated effective pH values close to pH 6 for all
      reaction conditions. Parallel to deepoxidation, the thylakoid lumen pH was
      estimated by the fluorescent dye pyranine.In LS thylakoids under coupled
      conditions the lumen pH did not drop below pH 6.7. At pH 6.7, no deepoxidase
      activity is expected based on the pH dependence of enzyme activity. The results
      suggest that deepoxidation activity is controlled by the pH in sequestered
      membrane domains, which, under localized proton coupling, can be maintained at pH
      6.0 when the lumen pH is far above pH 6.0. The extent of violaxanthin conversion
      (availability), however, appeared to be regulated by lumenal pH. Dithiothreitol
      sensitive nonphotochemical quenching of chlorophyll fluorescence was dependent on
      zeaxanthin and not related to lumenal pH. Thus, zeaxanthin-dependent
      quenching[mdash]known to be pH dependent[mdash]appeared to be triggered by the pH
      of localized membrane domains.

PMID- 12232440
TI  - Regulation of Maize Leaf Nitrate Reductase Activity Involves Both Gene Expression
      and Protein Phosphorylation.
AB  - Nitrate reductase (NR; EC 1.6.6.1) activity increased at the beginning of the
      photoperiod in mature green maize (Zea mays L.) leaves as a result of increased
      enzyme protein level and protein dephosphorylation. In vitro experiments
      suggested that phosphorylation of maize leaf NR affected sensitivity to Mg2+
      inhibition, as shown previously in spinach. When excised leaves were fed 32P
      labeled inorganic phosphate, NR was phosphorylated on seryl residues in both the
      light and dark. Tryptic peptide mapping of NR labeled in vivo indicated three
      major 32P-phosphopeptide fragments, and labeling of all three was reduced when
      leaves were illuminated. Maize leaf NR mRNA levels that were low at the end of
      the dark period peaked within 2 h in the light and decreased thereafter, and NR
      activity generally remained high. It appears that light signals, rather than an
      endogenous rhythm, account primarily for diurnal variations in NR mRNA levels.
      Overall, regulation of NR activity in mature maize leaves in response to light
      signals appears to involve control of gene expression, enzyme protein synthesis,
      and reversible protein phosphorylation.

PMID- 12232441
TI  - A Salicylic Acid-Binding Activity and a Salicylic Acid-Inhibitable Catalase
      Activity Are Present in a Variety of Plant Species.
AB  - Recently, it has been demonstrated that the salicylic acid (SA)-binding protein
      (SABP) from tobacco (Nicotiana tabacum) is a SA-inhibitable catalase (Z. Chen, H.
      Silva, D.F. Klessig [1993] Science 262: 1883-1886). Here we report the presence
      of SABP and SA-inhibitable catalase activity in Arabidopsis, tomato, and
      cucumber. The cucumber SABP has properties similar to the tobacco SABP, including
      binding affinity and specificity for SA.

PMID- 12232442
TI  - Achieving tobacco cessation: current status, current problems, future
      possibilities.
AB  - Assisting smokers to achieve tobacco cessation has always been difficult. The
      development of pharmacological approaches to the attainment of abstinence from
      tobacco usage has been very helpful, although our understanding of optimal
      clinical use is still incomplete and imperfect. Bupropion and nicotine therapy
      (NT) will help reduce the severity of nicotine withdrawal symptoms, whether used
      separately or in combination. Effectiveness is greater with the combination of
      drugs than with either drug alone. Nevertheless, the initial 'quit rate' is
      usually less than 50%, and there is a considerable decrease in the abstinence
      rate after the course of therapy has been completed. Effectiveness is increased
      if higher doses of NT are employed, with or without concomitant bupropion. Much
      remains to be learned about optimal doses, preferred durations of therapy and
      tapering, prevention and management of relapses, and selection of modes of
      delivery of NT. The discovery that nicotine dependence has a major genetic
      component has stimulated much interest and many research studies. The preliminary
      results are interesting, to say the least.

PMID- 12232443
TI  - Infant lung function testing--moving into the clinic now?

PMID- 12232444
TI  - Quit or die: nothing in between?

PMID- 12232445
TI  - Tidal volume forced expiration in asthmatic infants: reproducibility and
      reversibility tests.
AB  - BACKGROUND: The tidal volume forced expiration technique used in infants is
      considered as the first practical noninvasive method of assessing airway
      physiology in infants. However, its role has been discussed mainly due to the
      high variability of the derived parameters. OBJECTIVES: The aim of the study was
      to assess the reproducibility of a complete measurement with the tidal volume
      forced expiration technique in infants as measured by the maximal flow at FRC
      (V(max)FRC). A second aim was to evaluate the bronchial reversibility test in
      infant asthma. METHODS: Thirty infants with asthma were investigated with the
      tidal volume forced expiration technique twice with 10 min in between and a third
      time 10 min after inhalation of terbutalin 0.5 mg. RESULTS: The mean V(max)FRC in
      the first investigation was 285 ml.s(-1) (coefficient of variation 57%),
      unchanged in the second investigation and significantly lower than the mean
      predicted value of 404 ml.s(-1). The relative difference between the 2
      investigations of V(max)FRC was mean 10.5% (SD 8.4) of the absolute V(max)FRC
      value and independent of the size of this V(max)FRC value. The 95% confidence
      interval for individual changes would then be up to 27% (mean + 2 SD). The
      infants with the lowest V(max)FRC percent predicted decreased further in
      V(max)FRC after inhalation of the bronchodilator (p < 0.05). CONCLUSIONS: The
      tidal volume forced expiration technique was able to measure flow at late
      expiration with the same reproducibility as seen with spirometry in adults, even
      if the flow was low. We found the technique acceptable for clinical practice and
      research, but the results from reversibility tests are difficult to interpret. A
      significant change of V(max)FRC would, however, be 27% or more.

PMID- 12232446
TI  - Comparison of subjective and objective measures in recurrently wheezy infants.
AB  - OBJECTIVES: The aim of this study was to compare subjective measures (overall
      health assessment both by the study physician and the child's mother) with
      objective measurements of forced expiratory volumes (FEV(t)) and maximal flow at
      functional residual capacity V(max)FRC) in recurrently wheezy infants. METHODS:
      Sixteen wheezy infants (12 boys) aged 8-26 months were studied. A clinical
      assessment at visit 1 was followed by the run-in period during which day- and
      nighttime asthma symptom scores were obtained. The actual study period consisted
      of 2 visits when patient's lung function was assessed. The first of which was
      during an acute exacerbation (visit 2), while the second was when the infant was
      asymptomatic (visit 3). FEV(t) were obtained by the raised volume rapid thoracic
      compression technique (RVRTC) and V(max)FRC by the tidal volume rapid thoracic
      compression technique (TVRTC). RESULTS: Mean FEV(t) but not mean V(max)FRC were
      significantly lower at visit 2 compared to visit 3 (FEV(0.5): p = 0.005, and
      FEV(0.75): p = 0.002; V(max)FRC: p = 0.15) and correlated well with overall
      health assessment by the study physician (FEV(0.5): r = 0.82, and FEV(0.75): r =
      0.84), but not with the overall health assessment by the mother. CONCLUSIONS: We
      have shown in the present study that objective measurements of FEV(t) from a
      raised lung volume correlate well with the overall health assessment by the study
      physician; this was in contrast to measurements of V(max)FRC in the tidal volume
      range. We therefore conclude that the RVRTC technique is a feasible method to
      assess and monitor obstructive lung disease in infancy.

PMID- 12232447
TI  - Initiation of CPAP therapy for OSA: does prophylactic humidification during CPAP
      pressure titration improve initial patient acceptance and comfort?
AB  - BACKGROUND: Heated humidifiers (HH) enable effective treatment of upper airway
      dryness during nasal continuous positive airway pressure (nCPAP) therapy for
      obstructive sleep apnoea (OSA), but the role of prophylactic use of HH during the
      initiation of nCPAP treatment has not been studied so far. OBJECTIVES: The aim of
      the present study was to investigate whether prophylactic HH during the
      initiation of CPAP would result in improved initial patient comfort and
      acceptance. METHODS: In 44 consecutive, previously untreated OSA patients with no
      history of upper airway dryness, CPAP titration with and without HH was performed
      on two consecutive nights in a randomised order. The patients were interviewed
      after each treatment night in order to establish the comfort of the treatment,
      and, after the second treatment, they were asked which of the two nights they
      considered more pleasant, and which treatment they would prefer for long-term
      use. RESULTS: Following CPAP titration with HH, 32 patients (73%) claimed to have
      had a better night's sleep than usual (i.e. without CPAP treatment) compared with
      33 patients (75%) saying the same following CPAP treatment without HH. For 21
      patients (47.7%) treatment with HH was more pleasant, 23 (52.3%) saw no
      difference or said that treatment without HH was more pleasant. Nineteen patients
      (43.2%) gave preference to treatment with HH for long-term use, while 25 patients
      (56.8%) had no preference or said they would prefer treatment without HH.
      CONCLUSIONS: The use of HH during the initiation phase of CPAP treatment was
      associated neither with an initial improvement in comfort nor with greater
      initial treatment acceptance.

PMID- 12232448
TI  - Serial evaluation of high-resolution computed tomography findings in patients
      with idiopathic pulmonary fibrosis in usual interstitial pneumonia.
AB  - BACKGROUND: The development of well-matured fibrosis in usual interstitial
      pneumonia (UIP) is strongly associated with an unfavorable outcome of patients
      with idiopathic pulmonary fibrosis (IPF). However, differences in the rates of
      development are likely to result in variable clinical courses in IPF patients.
      OBJECTIVE: We tried to evaluate the progression of honeycombing and ground-glass
      opacity on CT using a scoring system, and to examine those serial changes in the
      clinical course of disease. METHODS: A hospital-based, retrospective cohort
      study. Twenty-three patients with IPF diagnosed as UIP by surgical lung biopsy
      were analyzed during the initial examination by scoring the presence of
      honeycombing (HC: range, 0-24) and ground-glass opacity (GG: range, 0-24) on CT
      scan. We also compared the serial changes observed in the CT scores (interval: 2
      42 months, 2-6 examinations). RESULTS: (1) The serial change in the HC score in
      treated patients (n = 10) was similar to that in untreated patients (n = 16); (2)
      the HC score at the time of the initial examination and the rate of HC
      progression were both higher in the non-surviving patients (HC 12.3 +/- 3.7, mean
      +/- SD; deltaHC 4.2 +/- 1.3 per year) than in the surviving patients (HC 5.8 +/-
      2.7; deltaHC 1.2 +/- 0.7 per year) (p < 0.05); (3) the GG score did not correlate
      with the HC score at any of the examinations; (4) the HC score was higher in the
      lower lung field than in the upper and middle lung fields. CONCLUSIONS: Scoring
      of the honeycombing and its serial changes using the high-resolution computed
      tomography scoring method was useful for predicting the prognosis in patients
      with IPF/UIP. Corticosteroid treatment did not prevent the progression of HC.

PMID- 12232449
TI  - High-resolution computed tomography findings are correlated with disease severity
      in asthma.
AB  - BACKGROUND: The structural changes in the airways of asthmatics are also referred
      to as remodeling and can be identified using high-resolution computerized
      tomography (HRCT). OBJECTIVES: To find out whether there are any abnormal HRCT
      features which can be attributed to asthma and their clinical correlates, and any
      differences of abnormal HRCT features between asthmatics and patients with
      chronic obstructive pulmonary disease (COPD). METHODS: We performed (HRCT) scans
      to assess airway remodeling in 160 nonsmoker asthmatics compared with 27 patients
      with COPD. RESULTS: Bronchial wall thickening, hyperlucency, centrilobular
      prominence, bronchiectasis, thick linear opacities and mucoid impaction were all
      correlated with disease severity in asthma. FEV(1) values were inversely
      correlated with bronchial wall thickening, hyperlucency, mucoid impaction, linear
      shadows, centrilobular prominence and bronchiectasis. In addition, thick linear
      opacities, mucoid impaction and bronchiectasis were more prominent in those
      patients with a long duration of asthma. Bronchial wall thickening, thick linear
      opacities, mucoid impaction, bronchiectasis and emphysema were more prominent in
      COPD patients compared with asthmatics. There was no difference with regard to
      age, mean values of FEV(1) and the duration of asthma between allergic and
      nonallergic asthmatics as well as abnormal HRCT findings. CONCLUSIONS: COPD
      patients have more prominent HRCT findings as compared with asthmatics. In the
      asthmatics, abnormal HRCT findings are more prominent with increased severity,
      decreased FEV(1) values and the duration of asthma. The remodelling of airways in
      allergic asthmatics did not differ from that in their nonallergic counterparts as
      determined by HRCT.

PMID- 12232450
TI  - A health-related quality-of-life comparison of formoterol (Oxis) Turbuhaler plus
      budesonide (Pulmicort) Turbuhaler with budesonide Turbuhaler alone and
      noncorticosteroid treatment in asthma: a randomized clinical study in Russia.
AB  - BACKGROUND: In Russia, current therapy for the long-term management of asthma is
      mainly nonsteroidal. This situation provides the opportunity to evaluate new
      asthma treatments in a patient cohort with little previous exposure to inhaled
      corticosteroids. OBJECTIVES: To compare the effect of formoterol (Oxis)
      Turbuhaler plus budesonide (Pulmicort) Turbuhaler with budesonide Turbuhaler
      alone, on the health-related quality of life (HRQL) of patients with mild to
      moderate asthma. METHODS: A double-blind, parallel-group, randomized, 12-week
      study compared formoterol Turbuhaler plus budesonide Turbuhaler and budesonide
      Turbuhaler alone with an open control group of the investigator's choice of
      noncorticosteroid therapy. Patients completed the Short Form 36 (SF-36) and the
      Asthma Quality of Life Questionnaire (AQLQ). RESULTS: The improvement in HRQL
      scores for patients treated with noncorticosteroids was significantly less (p <
      0.05) than those treated with formoterol plus budesonide and budesonide alone in
      all domains of the SF-36 and AQLQ with one marginal exception (budesonide versus
      investigator's choice, SF-36, Mental Component Scale, p = 0.053). Improvements in
      HRQL scores of formoterol plus budesonide, compared with budesonide alone,
      although generally higher, were not significantly different. Formoterol plus
      budesonide was more effective in improving lung function and reducing both
      symptoms and the need for relief terbutaline inhalation. CONCLUSION: Formoterol
      Turbuhaler plus budesonide Turbuhaler and budesonide Turbuhaler alone
      significantly improved the HRQL of patients with mild to moderate asthma compared
      with noncorticosteroid treatment.

PMID- 12232451
TI  - Gastroesophageal reflux and bronchial responsiveness: correlation and the effect
      of fundoplication.
AB  - BACKGROUND: A causal relationship between gastroesophageal reflux (GER) and
      asthma has been suggested. Should this be the case, one could expect treatment of
      GER to diminish bronchial sensitivity. There has been a lack of trials evaluating
      the efficacy of antireflux surgery on airway reactivity. OBJECTIVES: To
      investigate the correlation between GER and bronchial responsiveness, and to
      determine the efficacy of Nissen fundoplication on bronchial responsiveness and
      pulmonary function. METHODS: A methacholine inhalation challenge was performed on
      15 consecutive GER patients preoperatively and approximately 5 months after
      Nissen fundoplication. Airway responsiveness was quantified with a dose-response
      slope (DRS), calculated by dividing the decrease in FEV(1) (%) with the dose of
      methacholine administered (micromoles). RESULTS: A positive correlation between
      the severity of distal esophageal reflux and bronchial responsiveness was found
      (r = 0.83, p < 0.001). There was an improvement in FEV(1) after fundoplication (p
      = 0.03). All 3 asthmatic patients participating in the study presented with
      bronchial hyperresponsiveness (BHR) which improved clearly in all of these
      patients after fundoplication. This resulted in an apparent trend for DRS to
      improve when the entire study population was considered (p = 0.12). CONCLUSIONS:
      According to the current study there seems to be a positive correlation between
      the severity of distal esophageal reflux and bronchial responsiveness. These data
      suggest that operative treatment of GER may ameliorate BHR in asthmatic patients.
      Moreover, the results of the present study suggest that fundoplication may
      improve pulmonary function in patients with GER.

PMID- 12232452
TI  - Low-molecular-weight heparin versus unfractionated heparin in the treatment of
      patients with acute pulmonary thromboembolism.
AB  - BACKGROUND: Low-molecular-weight heparin (LMWH) appears to be as effective as
      unfractionated heparin (UFH) for both treatment and prophylaxis of deep vein
      thrombosis (DVT), but limited data are available for its use in acute pulmonary
      thromboembolism (PTE). OBJECTIVE: To determine whether enoxaparin, a LMWH, was
      clinically as efficient and safe as UFH in patients with a diagnosis of acute
      PTE. MATERIAL AND METHODS: After exclusion of those with massive forms, 59
      patients with acute PTE were randomly assigned to either subcutaneous enoxaparin
      given twice daily (1 mg/kg/dose) or adjusted dose intravenous UFH. Oral
      anticoagulant treatment was begun on the second day and was given for at least 6
      months. We compared the treatment regimens at day 8 and day 90 with respect to a
      combined end point of major bleeding, recurrent venous thromboembolism (VTE), and
      death. RESULTS: In the first 8 days of treatment, 1 of 30 patients assigned to
      receive UFH (3.3%) reached one of the end points (recurrence), as compared with
      none of 29 patients assigned to enoxaparin. Statistically this difference was not
      significant (p = 0.508). By day 90, 3 patients assigned to UFH (10%) had
      symptomatic recurrent VTE, as compared with 1 patient assigned to enoxaparin
      (3.4%). There was neither major bleeding nor death in the study groups. There was
      an absolute difference of 6.4 percentage points between the two treatment groups,
      but the difference was statistically not significant (p = 0.318). CONCLUSION:
      Initial subcutaneous treatment with enoxaparin appeared to be as effective and
      safe as UFH in acute PTE.

PMID- 12232453
TI  - Kinetics of 5-aminolevulinic acid-induced fluorescence in organ cultures of
      bronchial epithelium and tumor.
AB  - BACKGROUND: 5-Aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX)
      fluorescence improves the differentiation of tumor and normal tissue in the
      bladder, skin and brain. OBJECTIVE: The kinetics of 5-ALA-induced protoporphyrin
      IX (PPIX) fluorescence in organ cultures of normal human bronchial epithelium and
      cocultures of bronchial epithelium and tumor have been studied. METHODS: Cultured
      biopsies of bronchial epithelium were exposed for 5 or 15 min, or continuously to
      5-ALA. PPIX fluorescence was quantified for up to 300 min by spectroscopy.
      Cocultures of normal bronchial epithelium and a non-small-cell lung cancer cell
      line (EPLC-32M1) were incubated with 5-ALA. Space-resolved fluorescence
      microscopy was used to quantify PPIX fluorescence kinetics in the tumor and
      normal epithelium. RESULTS: In cultures of normal epithelium, PPIX fluorescence
      kinetics were shown to depend on the duration of exposure to 5-ALA. There was a
      trend to higher fluorescence intensities with longer exposure times. In
      cocultures of bronchial epithelium and tumor, increases of fluorescence intensity
      were significantly greater in the tumor. Best tumor/normal tissue fluorescence
      ratios were found between 110 and 160 min after exposure to 5-ALA. CONCLUSION:
      Data obtained in this coculture system of bronchial epithelium and tumor is
      valuable to optimize modalities of fluorescence bronchoscopy for the diagnosis of
      early bronchial carcinoma.

PMID- 12232454
TI  - Therapeutic bronchoscopy for treatment-resistant COPD.

PMID- 12232455
TI  - Harm reduction--a treatment approach for resistant smokers with tobacco-related
      symptoms.
AB  - Smokers with chronic obstructive pulmonary disease (COPD) appear to represent a
      hard-core group, and this presents a dilemma for chest physicians. A reduction in
      cigarette smoking benefits health, and nicotine replacement therapy (NRT) can aid
      smoking reduction. Hence we studied the efficacy of nicotine gum in helping hard
      core smokers with severe COPD to quit. Seventeen smokers with severe COPD (FEV(1)
      38-47% of predicted normal) who smoked >30 cigarettes/day but were unable to quit
      were encouraged to reduce their smoking as much as possible by using 4-mg
      nicotine gum. Five gradually reduced their daily tobacco consumption and, 18
      months after starting NRT, were smoking an average of 6 cigarettes/day while
      still using nicotine gum. Compared to baseline, their respiratory symptoms had
      improved, and both FEV(1) and FVC had increased. There was no improvement in
      pulmonary function in the group of smokers who did not reduce their cigarette
      consumption. No adverse events relating to nicotine occurred among the patients
      who used NRT to reduce their smoking. We propose that this reduction approach
      should be considered for patients with respiratory disease who are unable or
      unwilling to stop smoking.

PMID- 12232456
TI  - Two cases of 'asthma' revealing a diverticulum of Kommerell.
AB  - Among embryonic aortic vascular malformations, persistence of a right aortic arch
      and aberrant left subclavian artery associated with a diverticulum of Kommerell
      is rare, and is estimated to occur in 0.1% of the general population. We report
      two cases of diverticulum of Kommerell in which tracheal compression due to the
      vascular ring induced respiratory symptoms such as asthmatic dyspnoea. This
      reminds us that at least a chest X-ray should be performed in newly diagnosed
      asthmatic patients, focusing on the trachea and upper mediastinum. In case of
      vascular abnormality, angiography and magnetic resonance are the best
      investigations to define the abnormal anatomy and guide surgery.

PMID- 12232457
TI  - Right-to-left atrial shunt without pulmonary artery hypertension.
AB  - A 70-year-old woman without any history of pulmonary or cardiac disease developed
      breathlessness with severe arterial hypoxemia. Cardiac ultrasound examination and
      spirometry were normal. Cardiac catheterization and intravenous microbubble
      injection demonstrated an interatrial right-to-left shunt. The defect was closed
      surgically, and the patient recovered immediately. On surgery, the aorta was
      elongated, inducing an angulation of the interatrial septum and leading to the
      atrial septal defect just above the inferior vena cava.

PMID- 12232458
TI  - Weaning from mechanical ventilation by long-term nasal positive pressure
      ventilation in two patients with acute respiratory distress syndrome associated
      with pneumococcal sepsis.
AB  - Only few data concerning weaning by nasal positive pressure ventilation (NPPV)
      are available, and successful weaning by using NPPV in patients with acute
      respiratory distress syndrome (ARDS) and severe complications has not yet been
      described. Two cases with ARDS and both preexisting thoracopulmonary disease
      (infundibulum abnormality and suspected COPD) and associated complications
      (recurrent sepsis, acute renal failure, need for lobectomy, severe malnutrition)
      could not be weaned by invasive ventilatory techniques. Both patients presented
      with rapid shallow breathing and PaCO(2) values >60 mm Hg during intermittent
      trials of spontaneous breathing, although the primary pathology and associated
      complications had been resolved. Patients were successfully adapted on NPPV in a
      stepwise approach after 93 days and 67 days of invasive ventilation. In one
      patient withdrawal from NPPV was possible after 2 months. In the other patient
      the duration of daily ventilation could be significantly reduced from 18 to 6
      h/day after 9 months on NPPV. Therefore, patients with ARDS who cannot be weaned
      by invasive ventilatory strategies might be removed successfully from invasive
      mechanical ventilation by using NPPV even when there are preexisting
      thoracopulmonary disease and major complications during invasive ventilation.

PMID- 12232459
TI  - Necrotizing sarcoid granulomatosis presenting with elevated serum soluble
      interleukin-2 receptor levels.
AB  - A 52-year-old woman presented with a one-week history of low-grade fever and
      dyspnea. A CT scan showed multiple pulmonary nodules with cavitation, as well as
      bilateral pleural thickenings with effusions. A specimen resected by video
      assisted thoracoscopic surgery showed multiple confluent granulomas with central
      necrosis and granulomatous vasculitis. These findings were consistent with
      necrotizing sarcoid granulomatosis. An elevated serum soluble interleukin-2
      receptor level became normal following clinical and radiological improvement.
      This indicates that the serum soluble interleukin-2 receptor can be a useful
      marker for the clinical management of necrotizing sarcoid granulomatosis.

PMID- 12232460
TI  - Miliary lung lesions and multiple intracranial tumors in a 26-year-old woman.

PMID- 12232461
TI  - Diffuse alveolar hemorrhage associated with myeloperoxidase-antineutrophil
      cytoplasmic antibody induced by propylthiouracil therapy.

PMID- 12232462
TI  - Acquisition of serial complexity in speech production: a comparison of phonetic
      and phonological approaches to first word production.
AB  - Comparison was made between performance-based and competence-based approaches to
      the understanding of first word production. The performance-related frame/content
      approach is representative of the biological/functional perspective of phonetics
      in seeking explanations based on motor, perceptual and cognitive aspects of
      speech actions. From this perspective, intrasyllabic consonant-vowel (CV) co
      occurrence patterns and intersyllabic sequence patterns are viewed as reflective
      of biomechanical constraints emerging from mandibular oscillation cycles. A
      labial-coronal sequence effect involved, in addition, the problem of interfacing
      the lexicon with the motor system, as well as the additional problem of
      initiation of movement complexes. Competence-based approaches to acquisition are
      within the generative phonological tradition; involving an initial assumption of
      innate, speech-specific mental structures. While various current phonological
      approaches to acquisition involve consideration of sequence effects and
      intrasyllabic patterns, they do not adequately establish the proposed mental
      entities in infants of this age, and are nonexplanatory in the sense of not
      considering the causes of the structures and constraints that they posit.

PMID- 12232463
TI  - Principal components representation of the two-dimensional coronal tongue
      surface.
AB  - This paper uses principal components (PC) analysis to represent coronal tongue
      contours for the 11 vowels of English in two consonant contexts (/s/, /l/), based
      upon five replicated measurements in three sessions for each of 6 subjects.
      Curves from multiple sessions and speakers were overlaid before analysis onto a
      common (x, y) coordinate system by extensive preprocessing of the curves
      including: extension (padding) or truncation within session, translation, and
      truncation to a common x range. Four PCs plus a mean level allow accurate
      representation of coronal tongue curves, but PC shapes depend strongly on the
      degree of padding or truncation. The PCs successfully reduced the dimensionality
      of the curves and reflected vowel height, consonant context, and physiological
      features.

PMID- 12232464
TI  - Articulation of extreme formant patterns for emphasized vowels.
AB  - This study examined formant, jaw and tongue dorsum measurements from X-ray
      microbeam recordings of American English speakers producing emphasized vs.
      unemphasized words containing high-front, mid-front and low vowels. For
      emphasized vowels, the jaw position, regardless of vowel height, was lower, while
      the tongue dorsum had a more extreme articulation in the direction of the
      phonological specification of the vowel. For emphasized low vowels, the tongue
      dorsum position was lower with the acoustic consequence of F1 and F2 bunched
      closer together. For emphasized high and mid-front vowels, the tongue was more
      forward with the acoustic consequence of F1 and F2 spread more apart. These
      findings are interpreted within acoustic models of speech production. They also
      provide empirical data which have application to the C/D model hypothesis that
      both increased lowering of jaw and enhanced tongue gesture are consequences of a
      magnitude increase in the syllable pulse due to emphasis.

PMID- 12232465
TI  - An acoustic study of contrasting plosives and click accompaniments in Xhosa.
AB  - The phonetic manifestation of distinctive plosive types and click accompaniments
      in Xhosa was investigated with measurements of voice onset time (VOT), closure
      duration, voicing during closure, and burst amplitude. There is a high degree of
      interspeaker as well as token-to-token variability in the voiceless unaspirated
      plosives and clicks concerning their pronunciation with or without audible
      ejection. The plosives are much more frequently ejective than the corresponding
      clicks. If present, ejection is manifested by increased VOT, burst amplitude, or
      both. Duration of voicing during closure is substantial only in the implosive,
      but not in the 'voiced' plosives and clicks. After nasals the percentage of
      voicing during closure is high in 'voiced' plosives due to the very short closure
      duration found in that context; in the post-nasal 'voiced' clicks closure is
      mostly reduced to zero. Aspirated plosives and clicks in Xhosa show VOT values
      that are on average relatively long when compared to other languages. Closure
      duration tends to be shorter in aspirated plosives and clicks than in other
      categories.

PMID- 12232466
TI  - Explaining attitudinal ratings of Dutch rising contours: morphological structure
      vs. the frequency code.
AB  - In this article, two hypotheses were tested to explain attitudinal ratings like
      SURPRISE, SUGGESTION, REMINDER etc. of four rising nuclear contours observed in a
      Dutch question corpus and described as (a) H*L H%, (b) H* H%, (c) L*H H% and (d)
      L* H%. According to one hypothesis, the middle tones in (a) and (c) should be
      parcelled out, such that their absence produces contours (b) and (d),
      respectively, predicting communality of meaning within (a, c) that excludes (b,
      d). That is, (b, d) could be viewed as undershot variants of (a, c), with
      undershoot expressing a shade of meaning different from that of the fully
      realised pitch accents. This hypothesis was not confirmed by the data, though.
      The other hypothesis was based on the concept of the 'frequency code', which
      associates high/rising F(0) values with non-assertive behaviour and appeared to
      provide a much better model to predict listeners' ratings.

PMID- 12232467
TI  - Long-term postural abnormalities in benign paroxysmal positional vertigo.
AB  - Benign paroxysmal positional vertigo (BPPV) is a disorder in which patients
      suffer from acute rotatory vertigo due to the presence of free otoconial debris
      migrating into one or more semicircular canals during head movements and
      resulting in abnormal stimulation of the ampullary crest. A prolonged loss of
      equilibrium of unclear origin is also present. Static posturography is a useful
      tool for the study of postural control systems and their role in these
      abnormalities. The aim of the present study was to evaluate the frequency of body
      sway and long-term instability of BPPV patients by posturography frequency
      analysis. Twenty patients with canalithiasis of the posterior semicircular canal
      and 20 normal controls were subjected to static posturography. Informed consent
      was obtained from all subjects. Patients were tested 1 h after diagnosis, and 3
      days and 12 weeks after the characteristic Epley repositioning maneuver. Patients
      with BPPV showed significantly increased body sway both on lateral (X) and
      anteroposterior (Y) planes compared to normal subjects. Corporal oscillation with
      a broad-frequency spectrum was observed in both closed and open eye tests. The
      repositioning maneuver decreased the X plane body sway, while the anteroposterior
      sway was unchanged. Twelve weeks after treatment, a normalization of the
      anteroposterior sway was observed. Results of this study suggest that the long
      term postural disturbance associated with BPPV differs from the acute
      disequilibrium that subsides after canalith repositioning: the former is a
      sagittal plane/broad spectrum body sway, while the latter is primarily a frontal
      plane/low frequency sway. The Epley maneuver was shown to reduce frontal sway, a
      postural abnormality that might therefore be linked to posterior semicircular
      canal function. Conversely, the observed sagittal body sway was only partially
      relieved by the restoration of canal function, and therefore, may be more related
      to the chronic dizziness observed in these patients.

PMID- 12232468
TI  - The glycocalyx and stereociliary interconnections of the vestibular sensory
      epithelia of the guinea pig. A freeze-fracture, low-voltage cryo-SEM, SEM and TEM
      study.
AB  - In this study freeze fracture, low-voltage cryo-SEM, SEM and TEM were used to
      characterise the glycocalyx and stereociliary interconnections in the hair cell
      bundle of the vestibular sensory epithelia of the guinea pig. The glycocalyx
      resembles a shell-like structure separately surrounding each stereocilium and
      kinocilium over its entire length. The lateral interciliary connections emerge
      from the glycocalyx layer, forming an extensive extracellular network maintaining
      the stereocilia as a bundle. These connections are morphologically similar to the
      glycocalyx, and grossly oriented in the same direction, indicative of a role in
      the mechanical transduction system. The matrix material around the glycocalyx
      also appears to be morphologically similar to the glycocalyx, suggesting the
      glycocalyx to be even more important in the mechanical transduction system. The
      tip-links are covered with a layer, which is a continuation of the glycocalyx
      covering the stereocilia.

PMID- 12232469
TI  - Preservation of residual hearing in children and post-lingually deafened adults
      after cochlear implantation: an initial study.
AB  - OBJECTIVE: To investigate whether the residual hearing of severely hearing
      impaired children and adults could be preserved using the soft surgery approach.
      PATIENTS AND METHODS: This project employed a prospective study design. All
      testing and surgery took place in the Institute of Physiology and Pathology of
      Hearing, Warsaw, Poland. Twenty-six patients (7 children and 19 post-lingually
      deafened adults) with residual hearing were assessed. Subjects were assessed
      using conventional pure-tone audiometry at least 1 month prior to surgery.
      Cochlear implant surgery with a Med-El Combi 40/40+ standard electrode array was
      conducted, using the soft surgery approach. Pure-tone audiometry thresholds were
      re-assessed at least 1 month after surgery. The researchers assessed change in
      auditory thresholds using pure-tone audiometry to determine preservation of
      residual hearing. RESULTS: Sixteen of 26 patients (62%) retained their residual
      hearing within 5 dB HL of pre-operative scores. Only 5 of 26 patients (19%) lost
      all measurable residual hearing after cochlear implantation. This suggests that
      surgeons are often able to preserve residual hearing during cochlear implant
      surgery using the soft surgery technique. CONCLUSIONS: Preservation of residual
      hearing is an important consideration in cochlear implantation in the light of
      changing selection criteria for cochlear implant candidates, and as younger
      children are receiving implants. This is important, as we do not know yet the
      long-term effects of inner ear damage due to traumatic insertions of electrodes.
      This finding suggests a good prognosis for future possibilities of re
      implantation.

PMID- 12232470
TI  - Effect of tonsillectomy on serum concentrations of interleukins and TNF-alpha in
      patients with chronic tonsillitis.
AB  - We investigated serum interleukin (IL)-1beta, IL-4, IL-6, IL-8 and tumor necrosis
      factor (TNF)-alpha levels in 17 children aged 5-12 years (mean 7) with chronic
      tonsillitis before and after tonsillectomy. Cytokine concentrations were measured
      by enzyme-linked immunosorbent assay. IL-1beta and IL-6 levels were significantly
      higher than the control levels (p < 0.05) in preoperative serum samples. Other
      cytokine levels were within normal limits. After tonsillectomy, IL-1beta and IL-6
      levels were significantly reduced (p < 0.05). It is suggested that IL-1beta and
      IL-6 may be mediators which have a role in chronic tonsillitis disease and that
      tonsillectomy has a significant effect on preoperative IL-1beta and IL-6 serum
      levels.

PMID- 12232471
TI  - Thymidine labeling index in laryngeal squamous cell carcinoma in correlation with
      pTNM, age, histological grade and recurrence.
AB  - In this study, our aim was to investigate the prognostic features of the
      thymidine labeling index (TLI) in laryngeal squamous cell carcinoma (SCC). The
      TLI values in tumor tissues and adjacent healthy tissues were assessed in 40
      patients who had a pathological diagnosis of laryngeal SCC. The data were
      correlated with age, pTNM, histological grade and recurrence. The tissues (tumor
      and adjacent tumor-free tissue) obtained during surgery were labeled with (3)H
      thymidine. A statistically significant difference was observed between tumoral
      tissue and adjacent tumor-free tissue (p < 0.05), but we could not confirm any
      statistically significant correlation between TLI and age, pTNM, histological
      grade and recurrence. In conclusion, TLI in laryngeal SCC had no significant
      relation with the clinicopathological features, probably due to the variation in
      tissue sampling and for tumor-dependent reasons. TLI may assist in
      differentiating malignant from benign lesions.

PMID- 12232472
TI  - Rhinomanometry: an update.
AB  - Rhinomanometry has been widely accepted and used as an objective method to assess
      nasal patency for more than two decades. Much knowledge was obtained with its
      application in nasal pathophysiology and measuring techniques are still an issue
      for continuous improvement. Background, concept and current techniques, past,
      present and future, reliability, indications and contraindications are discussed
      in details. Special attention is paid to problems of definition, correlation
      between rhinomanometric data and subjective sensation of nasal patency and
      calibration. It is concluded that rhinomanometry applied together with acoustic
      rhinometry gives the most reliable objective information on nasal patency in an
      authentic rhinologic laboratory.

PMID- 12232473
TI  - Sentinel node biopsy: the technique and the feasibility in head and neck cancer.
AB  - Management of the clinically N(0) neck in head and neck squamous cell carcinoma
      is still under debate. Tumour spread to the neck is the most important prognostic
      factor in head and neck cancer patients. The sentinel node technique comprises
      the identification of the sentinel node by means of dye or isotope or a
      combination, and surgical removal followed by histological examination. We have
      reviewed the preliminary reports indicating that sentinel node identification is
      technically feasible in head and neck cancer surgery, i.e. in solitary and
      unilaterally oral and pharyngeal cancer stages T1 and T2 with clinical N(0).
      However, the existing reports enrole observational studies, thus randomised
      trials should be considered to gain maximum valid data to prove that sentinel
      node biopsy has an effect on parameters such as loco-regional control and
      survival.

PMID- 12232474
TI  - Lack of reported mutations in a Japanese case of toxic multinodular goiter.
AB  - We describe a toxic multinodular goiter that was subjected to genomic sequencing
      of the thyroid-stimulating hormone receptor and the alpha-subunit of the
      stimulatory guanine nucleotide-binding protein. No mutation was detected in
      either gene. While frequent occurrence of thyroid-stimulating hormone receptor
      gene mutations in toxic multinodular goiters has been reported in areas such as
      part of Europe with a relatively high prevalence of iodine deficiency, toxic
      multinodular goiters in areas with an abundance of dietary iodine such as Japan
      seem unlikely to involve mutations of this gene.

PMID- 12232475
TI  - Primary extramedullary plasmacytoma of the tongue base. Case report and review of
      the literature.
AB  - BACKGROUND: Primary extramedullary plasmacytomas (PEMP) are rare malignant
      neoplasms with a predilection for the head and neck. Eighty percent of all PEMP
      are located in this area. CASE REPORT: The authors present a case of lingual
      plasmacytoma in a 65-year-old man, diagnosed on biopsy and treated with external
      beam radiotherapy.

PMID- 12232476
TI  - Leprosy: otolaryngologist's perspective.
AB  - A patient with hemi-facial erythematous swelling as a result of borderline
      leprosy and reversal reaction is reported. This uncommon presentation of the
      disease poses initial diagnostic difficulties to the otolaryngologist. The
      otolaryngologist must be familiar with otolaryngologic manifestations of leprosy,
      since early diagnosis and treatment reduces the risk of transmission of the
      disease and may avoid permanent nerve damage.

PMID- 12232477
TI  - Diagnosis, management and surgical treatment of non-tuberculous mycobacterial
      head and neck infection in children.
AB  - The aim of this study was to present our experience with the clinical
      characteristics of non-tuberculous mycobacterial (NTM) head and neck lymph node
      infections, the use of modern diagnostic tools and the appropriate therapeutic
      measures. We have reviewed the cases of 14 Caucasian children with NTM head and
      neck lymphadenitis who were treated in our clinic in the last 5 years. Three of
      the patients were male and 11 were female. Their age ranged from 15 to 98 months
      (mean age 45.7 +/- 21.76 months). Cervical lymph nodes were involved in all of
      our cases, while the submandibular region was found to be the area mostly
      affected. Overlying skin was involved in 7 cases. Diagnosis was based on
      intradermal skin testing with specific antigens for atypical mycobacteria,
      histological examination and specimen culture. Skin tests were positive for NTM
      in all of the patients with a predilection for Mycobacterium avium complex. The
      diagnosis was confirmed by histological examination in 13 cases. Specimen culture
      was positive in 9 cases, most of them growing M. avium-intracellulare complex.
      Treatment included complete surgical excision of the affected lymph nodes and the
      overlying skin, as well as functional neck dissection when required. A second
      procedure was performed in 2 patients. Successful evaluation of NTM infections of
      the head and neck lymph nodes should include a detailed history, thorough
      physical examination and specific laboratory investigations. The treatment of
      choice is complete surgical excision of all affected tissue.

PMID- 12232478
TI  - Endoscopic transnasal resection of a juvenile angiofibroma using an
      ultrasonically activated scalpel.
AB  - We report a case of juvenile nasopharyngeal angiofibroma (JNA). A 19-year-old
      male came to our clinic complaining of severe nasal obstruction and epistaxis.
      Imaging investigations using computed tomography and magnetic resonance imaging
      techniques revealed a soft tissue mass in the nasopharynx with minimal extension
      to the pterygopalatine fossa. After embolization of the internal maxillary
      artery, we successfully performed endoscopic transnasal surgery for a JNA using
      an ultrasonically activated scalpel. Endoscopic follow-up for the 18 months after
      the surgical procedure revealed no evidence of recurrence or residual tumor.

PMID- 12232479
TI  - Congenital ranula. A report of two cases.
AB  - We report 2 unusual cases of congenital ranula in male Nigerian infants. Clinical
      examination could not discern the orifice of the submandibular duct on the
      affected sides, while a lower occlusal radiograph revealed no obvious calculi.
      Diagnosis was mainly by clinical presentation. The paper highlights possible
      aetiopathogenesis, clinical aspects and diagnostic features. Emphasis is laid on
      the need for careful evaluation of oral ranulas in order to discern their origin
      and provide appropriate treatment.

PMID- 12232480
TI  - Primitive malignant melanoma of the parotid gland.
AB  - Melanoma of the parotid gland is a very rare event: it can occur as a primary
      disease or as spread of the intraglandular nodes. The authors report a case and
      review the few cases of primary melanoma of the parotid gland reported in the
      literature.

PMID- 12232481
TI  - Surgical oncology in the interplay of surgical and nonsurgical disciplines.
AB  - Advances in surgical tumor therapy are founded on a very close interaction
      between different surgical subspecialties as well as the inclusion of surgical
      into modern multimodality treatment concepts. The ongoing development of surgical
      techniques, e.g. microsurgical flap transfers or pouch reconstructions of
      intestinal reservoirs, has increasingly enabled organ- and function-preserving
      surgery. In addition, new materials (e.g. modular tumor endoprosthesis) has
      supported this development. The broad application of the sentinel node technique
      in melanoma and breast cancer and also in gastrointestinal tract cancers opens
      new concepts of diagnosis and therapy for lymphatic metastasized tumors. Locally
      advanced tumors can be treated in neoadjuvant protocols to increase the
      resectability rate and the probability for local control as a prerequisite for
      long-term survival. Especially for metastatic disease, interventional treatment
      techniques such as laser-induced thermotherapy (LITT) or photodynamic therapy
      have added valuable options to surgical treatment.

PMID- 12232482
TI  - Recent advances in minimally invasive colorectal cancer surgery.
AB  - Laparoscopy has improved surgical treatment of various diseases due to its
      limited surgical trauma and has developed as an interesting therapeutic
      alternative for the resection of colorectal cancer. Despite numerous clinical
      advantages (faster recovery, less pain, fewer wound and systemic complications,
      faster return to work) the laparoscopic approach to colorectal cancer therapy has
      also resulted in unusual complications, i.e. ureteral and bladder injury which
      are rarely observed with open laparotomy. Moreover, pneumothorax, cardiac
      arrhythmia, impaired venous return, venous thrombosis as well as peripheral nerve
      injury have been associated with the increased intraabdominal pressure as well as
      patient's positioning during surgery. Furthermore, undetected small bowel injury
      caused by the grasping or cauterizing instruments may occur with laparoscopic
      surgery. In contrast to procedures performed for nonmalignant conditions, the
      benefits of laparoscopic resection of colorectal cancer must be weighed against
      the potential for poorer long-term outcomes of cancer patients that still has not
      been completely ruled out. In laparoscopic colorectal cancer surgery, several
      important cancer control issues still are being evaluated, i.e. the extent of
      lymph node dissection, tumor implantation at port sites, adequacy of
      intraperitoneal staging as well as the distance between tumor site and resection
      margins. For the time being it can be assumed that there is no significant
      difference in lymph node harvest between laparoscopic and open colorectal cancer
      surgery if oncological principles of resection are followed. As far as the issue
      of port site recurrence is concerned, it appears to be less prevalent than first
      thought (range 0-2.5%), and the incidence apparently corresponds with wound
      recurrence rates observed after open procedures. Short-term (3-5 years) survival
      rates have been published by a number of investigators, and survival rates after
      laparoscopic surgery appears to compare well with data collected after
      conventional surgery for colorectal cancer. However, long-term results of
      prospective randomized trials are not available. The data published so far
      indicate that the oncological results of laparoscopic surgery compare well with
      the results of the conventional open approach. Nonetheless, the limited
      information available from prospective studies leads us to propose that minimally
      invasive surgery for colorectal cancer surgery should only be performed within
      prospective trials.

PMID- 12232483
TI  - Significance of surgery in the multimodality treatment of rectal cancer.
AB  - Since the NIH recommendations in 1990 the majority of patients with rectal cancer
      are treated by a multimodality approach. The last decade has seen considerable
      improvements in the overall management of rectal cancer, therefore a certain
      reorientation seems justified. Although many questions remain to be answered,
      some general recommendations for the treatment of rectal cancer focussed on the
      small pelvis can be given. Surgery with total mesorectal excision is the standard
      therapy for cancers of the middle and low rectum in stages T1/2 N0. Adjuvant
      radiochemotherapy and shortterm pre-operative radiotherapy are both feasible
      approaches for the treatment of stage II and stage III rectal carcinomas. The
      superiority of either concept awaits clarifying randomised trials. Patients with
      T4 rectal cancers should undergo long-term neoadjuvant radiochemotherapy with
      consecutive oncological resection. The exact mode of the neoadjuvant regimen
      combining high remission rates with low treatment-associated morbidity needs
      further refinements. Local excision should be restricted to patients with well
      differentiated, less than semi-circumferential T1 carcinomas. Tumours with less
      favourable histologies should not be treated locally unless general patient
      conditions forbid oncological resections. In these instances, additional
      radiochemotherapy appears able to reduce the risk of local recurrence.

PMID- 12232484
TI  - Sentinel lymphonodectomy in gastrointestinal cancer--where are we now?
AB  - Up to now, no reliable methods for the pre- or intraoperative prediction of the
      nodal status are available in gastrointestinal cancer patients. Therefore, after
      the successful application of the sentinel lymph node concept in melanoma and
      breast cancer, ongoing research on this field is extended to gastrointestinal
      tumor entities. According to recent experiences, the most promising tumor
      entities are colon, gastric and anal cancer. First results with these patients
      indicate that the method could be a reliable predictor of the nodal status and,
      thus, may have important future implications for adjuvant therapy and the extent
      of surgery. The dye method for colon cancer and the combined method (dye and
      radiocolloid) for gastric cancer seem to be appropriate approaches, even when the
      general experience is still low. In rectal cancer, however, current experience
      failed yet to yield satisfying results. Up to now, anal cancer has not been a
      focus of publication, even when the concept seems to be very attractive for the
      evaluation of the inguinal lymph node status.

PMID- 12232485
TI  - Preoperative lymph-node staging in gastrointestinal cancer--correlation between
      size and tumor stage.
AB  - Our data suggest that lymph-node size is not a reliable indicator for lymph-node
      metastasis in gastric, esophageal, and colon cancer. Despite a significant
      difference in diameter of metastatic and non-metastatic nodes, the accurate
      evaluation of lymph-node metastasis in gastro-intestinal carcinoma cannot be
      determined by nodal size, because the majority of counted lymph nodes is ?5 mm
      and the frequency of small lymph-node metastases is high. Therefore imaging
      techniques using the size as criterion of nodal infiltration can not exactly
      assess the nodal status of patients with gastro-intestinal carcinomas. For
      rational lymphadenectomy, the value of sentinel node biopsy in gastro-intestinal
      cancer is now discussed. At the moment it is too early to apply sentinel node
      biopsy in order to reduce the extent of lymphadenectomy in these carcinomas [11].
      Recent interest has focused on PET scanning in the detection of lymph-node
      metastases. PET represents a potentially ideal imaging modality for malignancy.
      It allows a quick and simultaneous assessment of both local and distant sites
      and, as a result of avid uptake of the glucose moiety, may potentially identify
      small tumor loads. There are only limited experience in detecting lymph-node
      metastases in gastro-intestinal carcinoma and the results of the published
      reports are controversially discussed [12, 13]. Our data demonstrate a high
      frequency of small lymph-node metastases in gastro-intestinal carcinoma and
      suggest that a careful histological search for small lymph-node metastases should
      be undertaken to avoid false-negative lymph-node staging. These results emphasize
      that a reliable pathological staging of gastro-intestinal cancer must be based on
      a standardized systematic lymphadenectomy because lymph-node sampling based on
      lymph-node size is not sufficient.

PMID- 12232486
TI  - Intraoperative radiofrequency ablation using a 3D navigation tool for treatment
      of colorectal liver metastases.
AB  - BACKGROUND: Resection as the only potential cure for colorectal liver metastasis
      is limited by the size and the intrahepatic localization of lesions.
      Radiofrequency ablation (RFA) may extend the limitations of surgery. PATIENTS AND
      METHODS: 23 consecutive patients suffering from a total of 128 colorectal liver
      metastases were treated by resection and intraoperative RFA. All of these
      patients were irresectable by standard surgery due to volume and distribution of
      the lesions. 17 patients were treated by chemotherapy before RFA, with only 1
      patient showing partial regression of liver metastases. In 12 lesions a new 3D
      navigation tool was used, that allows a virtual overlay of the RFA probe in real
      time. RESULTS: 60 metastases were resected, 68 metastases were treated by RFA.
      There was no mortality, and complications occurred in 4 patients only
      (1??temporary encephalopathy, 3x cholangitis). Local tumor control according to
      CT scan was achieved by RFA in 93% of lesions up to 30 mm diameter (n = 45) and
      in 44% of lesions larger than 30 mm (n = 23). All ablations using the navigation
      tool were successful. After a mean follow-up of 8 +/- 5 months 12 patients are
      free of disease, 8 patients have either recurrent or new metastases, and 3
      patients died of progressive disease. The estimated median survival time is 18
      months (95% confidence interval 13-22 months). CONCLUSIONS: Intraoperative RFA of
      colorectal liver metastases in combination with hepatic resection is safe. Up to
      a lesion size of 30 mm a reliable treatment with RFA is possible. The navigation
      aid increases the reproducibility of the procedure.

PMID- 12232487
TI  - Radio-chemotherapy as a preoperative treatment for advanced rectal cancer.
      Evaluation of down-staging and morbidity.
AB  - BACKGROUND: The standard therapy for patients with clinically resectable rectal
      cancer is generally considered to be surgery. If the patient is diagnosed with
      advanced disease, postoperative radio-chemotherapy (RCT) is usually recommended.
      In our study we aimed to investigate and analyze the effectiveness and toxicity
      of preoperative pelvic radiotherapy in combination with 5-fluorouracil (5-FU) in
      locally advanced rectal cancer. PATIENTS AND METHODS: From June 1999 to September
      2001 we evaluated 50 consecutive patients [37 male and 13 female; average age
      65.1 (range 46-79.5) years] with locally advanced rectal carcinoma. 32 patients
      were staged as uT3, 14 as uT4, and 4 as uT2. Regarding N-staging, 22 patients
      were diagnosed as uN0. 2 patients had distant metastases, with liver metastases
      in both instances. Conformal irradiation was performed with a box technique (4
      field technique) with a dose of 45 Gy (5 x 1.8 Gy per week for a total of 25
      sessions). From days 1-5 and 29-33, all patients received 5-FU (500 mg/m(2 ) per
      day, as a continuous i.v. injection). RESULTS: Remission was observed in 28
      patients (56%), with down-staging of at least one T-stage. A better success rate
      was achieved for patients with deep-seated tumors (64% of the patients in this
      group). Complete remission was observed in 4 patients (8.0%) and progression in 3
      (6.0%). 15 patients had no detectable change in tumor staging (30.0%). A surgical
      R0 resection could be achieved in 43 patients, an R1 resection (minimal margin)
      in 7. Side effects and toxicity (common toxicity criteria) of RCT included grade
      I-II dysuria in 5 patients (10%), grade I-II diarrhea in 20 patients (40%), and
      severe diarrhea in 2 patients (4.0%). Grade I-II skin reaction was noticed in 22
      patients (44.0%), severe skin reaction only in 1 patient. Regarding acute
      postoperative morbidity, abscess and fistula formation was noted in 8 patients
      (16.0%), with anastomosis leakage in 7 (14%). CONCLUSION: Preoperative
      radiotherapy appears to be a feasible therapeutic approach with moderate toxicity
      and the potential to induce down-staging. The data presented in this study
      confirm the preliminary reports on this neoadjuvant treatment.

PMID- 12232488
TI  - Second-Line Treatment of Advanced Colorectal Cancer with a Biweekly Oxaliplatin
      plus Irinotecan Combination Regimen.
AB  - BACKGROUND: Both oxaliplatin and irinotecan have demonstrated antitumor activity
      in pretreated colorectal cancer; experimental and early clinical data suggest
      that these two drugs may act synergistically. The aim of this study was to
      document the therapeutic index of a biweekly combination regimen in patients with
      metastatic colorectal cancer failing prior palliative first-line chemotherapy
      with raltitrexed. PATIENTS AND METHODS: In this study 27 patients with metastatic
      colorectal cancer were analyzed, who progressed while on or within 6 months after
      discontinuation of palliative first-line chemotherapy with raltitrexed. They
      received oxaliplatin 85 mg/m(2) and irinotecan 150 mg/m(2) both given on days 1
      and 15 every 4 weeks. RESULTS: The confirmed overall response rate was 37% (95%
      confidence interval, 19.4-57.7%), including 2 complete and 8 partial remissions.
      12 additional patients (44.4%) had stable disease, and in only 5 cases (18.5%)
      disease progression was not influenced by chemotherapy. The median progression
      free survival for all 27 patients was 8 months (range, 1-16+ months), and 16
      patients (59%) are still alive after a median follow-up time of 12.5 months.
      Hematologic adverse reactions, specifically leukocytopenia and neutropenia, were
      common though generally mild to moderate with grade 4 toxicity occurring in only
      2 cases. The most frequent non-hematologic adverse events included
      gastrointestinal symptoms; severe nausea/emesis and diarrhea, however, were noted
      in only 2 and 3 patients, respectively. CONCLUSIONS: Our data suggest that the
      described biweekly combination regimen of oxaliplatin and irinotecan has
      substantial antitumor activity in patients with progressive, raltitrexed
      pretreated metastatic colorectal cancer. Because of its favorable toxicity
      profile, further evaluation of this combination seems warranted.

PMID- 12232489
TI  - Cytoprotective effect of amifostine in radiation-induced acute mucositis - a
      retrospective analysis.
AB  - PURPOSE: To study the cytoprotective impact of amifostine against acute radiation
      mucositis. PATIENTS AND METHODS: A total of 117 cancer patients with carcinomas
      localized in pelvic organs, lung and head and neck were entered into this study.
      In a retrospective way, and in order to minimize the bias related to the
      investigator, 138 patients as historical controls were randomly selected from a
      database in our hospital. Acute radiation-induced gastrointestinal mucositis,
      esophagitis and stomatitis were assessed using the common toxicity criteria
      scale. The most severe grade recorded was evaluated as the final morbidity score
      for this patient. Mean toxicity score (MTS) was the mean value of recorded acute
      radiation toxicity. Mean interruption time (MIT) was the mean value of recorded
      interruption time due to radiation toxicity. RESULTS: A significantly reduced
      severity of symptomatology related to oral, esophageal and rectal mucosa was
      noted in the amifostine group (group A) (p < 0.05, chi-square test). Furthermore,
      a significant reduction of MTS as well as MIT was observed in group A versus the
      historical controls (group B) (p < 0.05, Mann-Whitney U test). CONCLUSION: The
      administration of amifostine seems to protect patients against radiation-induced
      mucositis, but further investigation with randomized trials is needed.

PMID- 12232490
TI  - Seminoma metastases mimicking primary pancreatic cancer.
AB  - BACKGROUND: A case of seminoma clinical stage III, arising from the right testis
      and mimicking a primary pancreatic malignancy is reported. CASE REPORT: A 57-year
      old male patient presented with obstructive jaundice. He suffered from recurrent
      abdominal pain and significant weight loss over the past 4 months. Abdominal CT
      scan showed a tumor in the head of the pancreas and multiple pathologically
      enlarged peripancreatic lymph nodes. In the laboratory findings there were signs
      of cholestasis and infection. A laparoscopic biopsy out of a suspicious lesion of
      the head of the pancreas and a surrounding lymph node was done. Histopathological
      examination reported metastasis of seminoma in a lymph node. Further laboratory
      findings showed an elevation of the human placental alkaline phosphatase (HPLAP)
      and urological examination revealed a suspect right testis. The patient underwent
      castration of the right testis and histopathological examination confirmed a
      seminoma. 4 cycles of chemotherapy including cisplatinum, etoposide and bleomycin
      led into complete response that is still ongoing. CONCLUSION: This case shows a
      seminoma with metastases at retroperitoneal site, mimicking a primary pancreatic
      neoplasm. It provides an example of the possibility of an uncommon clinical
      appearance of seminoma metastases and again underlines the importance of exact
      radiological and histopathological examination to distinguish between curable and
      incurable tumor.

PMID- 12232491
TI  - Mistletoe extracts standardised in terms of mistletoe lectins (ML I) in oncology:
      current state of clinical research.
AB  - PURPOSE: The aim of this review is to present the current state of clinical
      oncological research on mistletoe extracts standardised in terms of the active
      substance mistletoe lectin. METHODS: This review focuses on studies with clearly
      defined mistletoe extracts standardised in terms of mistletoe lectins I, II, and
      III (calculated as mistletoe lectin I, ML I) which belong to the category of
      rational phytotherapy. That means that studies with anthroposophic or homeopathic
      drugs will not be included. RESULTS: There are several preclinical studies that
      show a cytotoxic and immunostimulating effect of mistletoe extracts,
      predominantly on the cellular immune system. The clinical database, however, is
      not as good as the experimental results. So far, no direct anticancer action or
      any improvement in time to tumour progression or overall survival in cancer
      patients has been seen. The first results of a randomised phase III study suggest
      that additive administration of a mistletoe preparation may improve the quality
      of life. CONCLUSION: Mistletoe therapy has not gained an established place in
      oncology. Further, well-planned randomised clinical investigations will be
      necessary to verify the first positive findings with regard to an improvement of
      quality of life in cancer patients.

PMID- 12232492
TI  - Chronic epicondylitis: effects of real and sham acupuncture treatment: a
      randomised controlled patient- and examiner-blinded long-term trial.
AB  - OBJECTIVE: The clinical long-term effectiveness of real and sham acupuncture
      treatment on differentiated pain measurement was evaluated in chronic lateral
      epicondylitis, an example of a tendomyotic disorder. METHODS: Randomised,
      examiner- and patient-blinded controlled clinical study. OUTCOME MEASUREMENT:
      pain at rest, pain on movement, pain on exertion, frequency and duration of pain.
      Real acupuncture (n = 23) was tested versus invasive sham acupuncture (n = 22).
      Ten treatments were given (2 treatments/week). Patients were examined at baseline
      (E1) as well as 2 weeks (E2), 2 months (E3) and 1 year (E4) after the end of
      treatment. In the treatment with real acupuncture, acupuncture points were
      selected and mechanically stimulated while in the sham group non-acupuncture
      points were selected. RESULTS: There was no significant difference between the
      groups at baseline for any outcome parameter. Two weeks, 2 months and 1 year
      after the end of treatment there were significant reductions in all pain
      variables compared to baseline. At the first follow-up, significant group
      differences were registered for pain on motion and pain on exertion in favour to
      the real acupuncture group. These differences in pain intensity between the
      groups were no longer significant at the 2 months and 12 months follow-ups.
      CONCLUSION: The results suggest that, in the treatment of chronic epicondylitis,
      the selection of so-called real acupuncture points gives better results than
      invasive sham acupuncture at early follow-up. This additional effect can be
      interpreted as a specific effect of real acupuncture.

PMID- 12232493
TI  - Effect of sulfur baths on antioxidative defense systems, peroxide concentrations
      and lipid levels in patients with degenerative osteoarthritis.
AB  - BACKGROUND: Due to possible antiinflammatory effects, sulfur baths are widely
      used for the treatment of rheumatic diseases. Previously it was demonstrated that
      drinking cures with sulfur can improve the antioxidative defense system and lower
      the peroxide levels of patients with chronic degenerative osteoarthritis.
      OBJECTIVE: This study therefore sought to investigate the effect of 3-week
      therapy with sulfur baths on antioxidative defense systems, peroxide
      concentrations, and lipid levels in patients with degenerative osteoarthritis.
      PATIENTS AND METHODS: After randomization one group of patients (n = 19) received
      sulfur baths during their stay at a health resort (sulfur group), whereas the
      other age-matched patient group served as controls (n = 19, control group), only
      receiving spa therapy. Total cholesterol levels, HDL, LDL, triglycerides and the
      antioxidative status, glutathione peroxidase, and superoxide dismutase (SOD)
      activities, and peroxide concentration, as an oxidative stress parameter, were
      evaluated at the begin and end of therapy. RESULTS: A 17.2% decline in peroxide
      concentrations (p = 0.10, n.s.) and significant lower SOD activities (p < 0.001)
      were detected in the sulfur group at the end of the therapy. Until the end of
      therapy total cholesterol levels changed differentially (p = 0.007) in the sulfur
      group (from 229.11 +/- 34.47 mg/dl to 217.46 +/- 40.45 mg/dl) and in the control
      group (from 197.63 +/- 34.66 mg/dl to 207.95 +/- 33.02 mg/dl). A similar
      significant group difference was found for LDL (p = 0.017), with a 5.9% reduction
      in the sulfur group and a 6.1% increase in the control group. Triglyceride
      concentrations were nonsignificantly reduced in both groups after 3 weeks at the
      health resort (sulfur group 11.2%, control group 20.2%). HDL values only
      minimally changed in both groups. CONCLUSIONS: The results presented here suggest
      that a sulfur bath therapy could cause a reduction in oxidative stress,
      alterations of SOD activities, and a tendency towards improvement of lipid
      levels.

PMID- 12232494
TI  - [Short-term therapeutic fasting in the treatment of chronic pain and fatigue
      syndromes--well-being and side effects with and without mineral supplements].
AB  - BACKGROUND: Fasting followed by vegetarian diet has shown to be an effective
      treatment for rheumatoid arthritis, moreover fasting is frequently used as an
      adjunctive treatment in chronic pain and stress/exhaustion syndromes. Data on
      well-being and the frequency of side effects during fasting are mostly
      retrospective. Mineral supplements are frequently used in order to compensate for
      fasting-induced tissue acidosis and to reduce side effects. There are only
      limited data that support this practice. OBJECTIVE: To study the effects of oral
      mineral supplements on common side effects and well-being during short-term
      fasting. PATIENTS AND METHODS: 209 consecutive inpatients with chronic
      pain/exhaustion syndromes were recruited. In a controlled non-randomised study
      design all patients underwent fasting (250 kcal; 3 l fluid intake/day) over 7
      days, in study phase 1 without (n = 103) and in study phase 2 with (n = 106)
      concomitant prescription of standardised oral mineral supplements (3 x 2 to 3 x 3
      Bullrich's Vital). Weight, blood pressure and urinary pH were recorded daily.
      Well-being and mood as well as common side effects (i.e. fatigue, hunger, heart
      burn, headache) were assessed with standardised self-reports. RESULTS: Baseline
      characteristics of the 209 patients (mean age 54.7 +/- 10.5 years; 83.3% female)
      were balanced. Both groups showed a fasting-induced decrease of blood pressure, a
      slight decrease in mood and well-being on days 3 and 4 with consecutive increase
      and moderate hunger, i.e. in the evening. Side effects and general tolerability
      of fasting as well as well-being and mood were not different between the groups.
      There were no serious side effects in both groups. CONCLUSIONS: Short-term
      fasting in inpatients with pain and stress syndromes is safe and well tolerated,
      concomitant mineral supplements have no additive benefit.

PMID- 12232495
TI  - [The scientific effectiveness of identification of a therapeutically active
      ingredient of high potencies].
AB  - It is shown that scientific modelling of therapeutically active ingredients of
      high potencies is possible if some consequences from quantum theory are accepted.
      This modelling is distinguished from the description of non-locality in non
      physical context.

PMID- 12232496
TI  - Functional imaging of the auditory system: the use of positron emission
      tomography.
AB  - Modern brain imaging methods now afford unprecedented opportunities for the in
      vivo study of central auditory system function. Positron emission tomography
      (PET) has been used as a functional imaging technique for more than 15 years to
      study the distribution of cerebral haemodynamic changes associated with auditory
      stimulation, in subjects with normal and abnormal auditory function. Many of
      these studies concern processes related to, but not identical with, audition,
      such as speech perception, melodic processing and directed attention.
      Additionally, PET has been used to explore auditory perception in clinical
      populations such as cochlear implantees, neurosurgical candidates and people with
      tinnitus and auditory hallucinations. The spatial resolution of PET does not
      appear sufficient to address questions of a fine anatomical grain, e.g. exploring
      functional specialization within the primary and secondary auditory cortex.
      Nevertheless, PET has considerable potential as a tool in basic research on, and
      clinical assessment of, many auditory phenomena. Although functional magnetic
      resonance imaging can now be used for many studies for which formerly only PET
      was suitable, PET still possesses unique advantages. For example, it permits
      acquisition of data from inferior frontal and anterior temporal areas, can be
      used with subjects with cochlear and other implants (such as pacemakers) and can
      be used to map neurochemical pathways and receptors.

PMID- 12232497
TI  - Identification of differentially expressed cDNA clones from gerbil cochlear outer
      hair cells.
AB  - In order to identify genes that are associated with outer hair cell(OHC)-specific
      function, a plasmid library enriched with OHC-specific gene products was
      constructed using single cell-type-specific complementary DNA (cDNA) and a PCR
      subtractive hybridization strategy. As a first step, we created separate OHC and
      inner hair cell (IHC) cDNA pools from individually collected cells using a
      nonspecific reverse transcription polymerase chain reaction. Next, the OHC cDNA
      was subtracted against IHC cDNA using a PCR-based subtractive technique. IHCs and
      OHCs share many common features, making IHC cDNA an ideal 'driver' to 'subtract
      away' common hair cell gene products and enrich differentially expressed cDNAs,
      including OHC-specific genes. The subtracted OHC cDNAs were then cloned to
      generate an OHC - IHC subtracted cDNA plasmid library. Finally, a differential
      screening procedure was performed, resulting in 477 differentially positive
      clones. After analysis of these 477 clones, 50 known genes were identified,
      including two previously known OHC-specific proteins: oncomodulin and the
      recently described motor protein prestin. An additional 84 novel clones were also
      found. As this library of cDNA fragments represents differentially expressed
      genes in OHCs, it can be used as starting material for isolation and
      characterization of a complete set of OHC gene products, an important step in
      investigating normal and abnormal cochlear function.

PMID- 12232498
TI  - The cytocaud: a hair cell pathology in the waltzing Guinea pig.
AB  - The waltzing guinea pig displays severe inner ear dysfunction that involves both
      an auditory and a vestibular manifestation. The aim of this study was to
      characterize a pathological tail-like extension of the vestibular hair cells, the
      cytocaud. Our data suggest that nearly all type I hair cells in the waltzing
      guinea pig have cytocauds, which appear as membrane-bound tails containing
      mitochondria and cytoplasm that proceed in a basal direction toward the basement
      membrane. The extensions either attach to the basement membrane or penetrate it,
      and further proceed into the extracellular matrix. A core made of a thick and
      long (30 microm) actin-rich structure supports the slender long process. The
      actin core has cross-links that are periodically placed along the length of the
      cytocaud. Our data suggest that the cytocauds in vestibular hair cells of the
      waltzing guinea pig are highly organized structures associated with a failure to
      detach from the basement membrane.

PMID- 12232499
TI  - Calcitonin gene-related Peptide and choline acetyltransferase colocalization in
      the human vestibular periphery.
AB  - Within the vestibular system, calcitonin gene-related peptide (CGRP) has been
      localized in the efferent terminals and their brainstem neuronal cell bodies in
      several animal models. Presently, very few studies have verified these findings
      in the vestibular system in adult primates or humans. CGRP immunoreactivity
      (CGRPi) and its colocalization with choline acetyltransferase immunoreactivity
      (ChATi) in human vestibular end organs and Scarpa's ganglion were studied using
      polyclonal antibodies against CGRP and ChAT, at the light-microscopic level. The
      CGRPi axons ramified to produce numerous CGRPi terminals throughout the
      neurosensory epithelium of the maculae and cristae, primarily in the basal and
      midbasal areas. Numerous CGRPi efferent terminals made contact with both type II
      vestibular hair cells and the afferent chalices surrounding type I vestibular
      hair cells. All CGRP immunoreactive fibers also exhibited ChATi. As in the animal
      models, no CGRPi was found within Scarpa's ganglion. This study provides evidence
      for CGRPi in the human vestibular periphery and validates the biomedical
      relevance of the current animal models.

PMID- 12232500
TI  - Knowledge of stimulus repetition affects the magnitude and spatial distribution
      of low-frequency event-related brain potentials.
AB  - Rate effects are defined as a reduction in amplitude of an evoked brain response
      with increasing stimulus frequency. In auditory paired-stimulus paradigms, a
      smaller amplitude evoked response to the second stimulus at a latency of 50 ms
      has been proposed to index a preattentive sensory gating mechanism. The present
      study investigated the possibility that expectancy and/or attentional biases
      could alter evoked potentials associated with rate effects. EEG data were
      recorded from 30 channels while subjects received 240 trials of 1, 2 or 3 click
      stimuli (with successive stimuli being separated by 500-ms intervals). Half of
      the subjects knew (blocked condition) and half of the subjects did not know
      (mixed condition) how many stimuli they would receive on a given trial. Subjects
      in the blocked condition had a significantly larger rate effect than subjects in
      the mixed condition. This effect was present only for low-frequency components of
      the event-related brain potential (ERP; below 10 Hz) and occurred from 30 to 60,
      90 to 160 and 190 to 260 ms after stimulus presentation (P(1)-N(1)-P(2) complex).
      Mixed condition subjects also had larger contributions to their ERPs from
      temporal channels. These results suggest that the rate effect can be
      significantly altered by expectancy, and they are inconsistent with the thesis
      that ERPs near 50 ms in a paired-stimulus paradigm solely index a preattentive
      sensory gating mechanism.

PMID- 12232501
TI  - Cellular longevity: role of apoptosis and replicative senescence.
AB  - Cellular longevity refers to the lifespan of an individual cell. Normal cells
      have a finite lifespan and typically die by undergoing apoptosis, or enter into a
      state of irreversible growth arrest, termed replicative senescence, at the end of
      that lifespan. The lifespan of a cell is a balance between pro-survival/anti
      apoptotic and pro-apoptotic death-promoting factors. The role of heat shock
      proteins, Bcl-2 family members, antioxidant molecules, and telomere length and
      telomerase activity in the regulation of apoptosis and replicative senescence,
      will be discussed.

PMID- 12232502
TI  - Decline in the expression of C4 binding protein alpha-chain gene during ageing of
      the rat liver.
AB  - It appears that consistent changes in the levels of activity of a small cohort of
      genes (probably less than 1% of all active genes) occur in all mammalian cells
      during ageing. We have studied this phenomenon in rat liver using an optimised
      form of differential display. During this investigation we observed one gene
      which exhibited a decline in expression in livers from young adult (6 months) to
      aged adult (24 months) animals. The differential expression of this gene was
      confirmed by single strand conformational polymorphism (SSCP) gel analysis and
      Northern blotting. Densitometry of the latter indicated that there was a decline
      of 35% in its expression with age. Characterisation of the isolated PCR fragment
      demonstrated it to code for the alpha subchain of the complement 4 binding
      protein (C4BP). The C4BP is a key regulatory protein of the complement system and
      this observation therefore indicates that a decline in the efficiency of the
      complement system may be an important factor in the overall decline in immune
      function that has been observed during ageing.

PMID- 12232503
TI  - A single-stage mechanism controls replicative senescence through Sudden
      Senescence Syndrome.
AB  - Normal human cells have a finite proliferative potential in vitro. However, some
      DNA viral proteins, such as SV40 Tg, can alter this and extend the lifespan after
      which the cells enter crisis, a period when massive cell death occurs. Based on
      these observations, a two-stage model for cellular senescence has been proposed
      with a distinct function for each stage. Mortality stage 1 (M1) is hypothesized
      to cause cell senescence and is activated near the end of the proliferative
      lifespan, whereas Mortality stage 2 (M2) involves an independent mechanism that
      causes failure of cell division and crisis. Here, we present experimental
      evidence demonstrating that inhibition of the onset of Sudden Senescence Syndrome
      (SSS) by SV40 Tg greatly reduces the appearance of senescent cells in the culture
      and results in an increase in the population doublings (PD) to that of the number
      of cell generations (CGs). This is what causes the observed lifespan extension.
      Our results also provide an explanation for 'additional' telomere shortening
      during this 'extended' lifespan. Based on these observations, we suggest that
      crisis or M2 cannot be considered a 'mechanism' controlled by a specific set of
      genes. Our results do not support the previously proposed two-stage model and
      indicates SSS as the single, primary mechanism of cell senescence. Several recent
      findings from other laboratories that support our previously published self
      recombination model of the molecular mechanisms that control SSS are discussed.

PMID- 12232504
TI  - Role of heme oxygenase-1 in the biogenesis of corpora amylacea.
AB  - Corpora amylacea (CA) are glycoproteinaceous inclusions that accumulate in the
      human brain during normal aging and to a greater extent in Alzheimer's disease.
      We previously demonstrated that, in cultured rat astroglia, cysteamine (CSH)
      upregulates heme oxygenase-1 (HO-1) and promotes the transformation of normal
      mitochondria into CA-like inclusions. In the current study, primary cultures of
      neonatal rat astroglia were exposed to 880 micro M CSH for three months in the
      presence or absence of dexamethasone, a suppressor of HO-1 gene transcription.
      Cells were double-labeled with periodic acid-Schiff reagent (PAS) and antisera
      against ubiquitin, HO-1, or a mitochondrial epitope. CA were quantified and their
      immunostaining characteristics analyzed using confocal microscopy. HO-1
      immunofluorescence was more abundant in cultures exposed to CSH alone relative to
      untreated control cultures and cultures exposed to both CSH and dexamethasone.
      Mature CA appeared as large (5-50 microM), spherical or polygonal, intensely PAS
      positive inclusions within glial cytoplasm or deposited extracellularly. The
      inclusions manifested intense rim and, less commonly, homogeneous or stippled
      patterns of immunoreactivity for ubiquitin, HO-1, and the mitochondrial marker.
      Monolayers exposed to CSH exhibited 660% more CA relative to untreated controls
      (P < 0.05). Numbers of CA in cultures exposed to CSH were diminished by co
      administration of 50 microg/ml dexamethasone (P < 0.05 relative to CSH alone) or
      100 microg/ml dexamethasone (P < 0.05 relative to CSH alone). Numbers of CA in
      cultures co-treated with CSH and 50 microg/ml dexamethasone or 100 microg/ml
      dexamethasone were not significantly different from untreated control values. Up
      regulation of HO-1 may contribute to the formation of CA in aging astroglia.

PMID- 12232505
TI  - Life span: does the limit to survival depend upon metabolic efficiency under
      stress?
AB  - Survival to old age in natural populations is enhanced by high vitality and
      resilience which depends upon substantial homeostasis and energetic amd metabolic
      efficiency underlain by genes for stress resistance. Under this assumption
      increased longevity follows from primary selection for stress resistance where
      stress targets energy carriers. Furthermore old and young fitness should be
      correlated irrespective of age under the stressful selection regime of natural
      populations. In contrast, antagonistic pleiotropy is most likely under the less
      rigorous selection regime of well-nourished humans and laboratory populations
      surviving to old age. Similarly, hormesis for longevity, for example from a mild
      temperature stress or restricted food intake is most likely under benign
      environmental conditions. Assuming that aging in natural populations depends upon
      ecological circumstances, large evolutionary increases in life span are unlikely
      under the stress theory of aging since organisms are frequently close to their
      limits of survival where metabolic efficiency is at a premium. Exceptions can
      occur in island populations and for mutants under laboratory conditions since the
      risks from environmental hazards are reduced, and life span becomes extended as a
      consequence. In modern human populations, selection for stress resistance is less
      intense than in earlier times which should be permissive of the accumulation of
      stress-sensitive mutants under the mutation-accumulation theory of aging.
      However, this process is ultimately likely to restrict the evolution of life-span
      extensions in the future especially if abiotic conditions deteriorate, when
      survival would depend more directly on metabolic efficiency under stress.

PMID- 12232506
TI  - Application of the yeast two-hybrid system in molecular gerontology.
AB  - Most -- if not all -- proteins are bound to interact with other proteins to exert
      their function, and thus the identification of the interaction partners of a
      protein is vital in proteomics. The yeast two-hybrid system is a popular and
      effective tool for studying protein-protein interactions. Although the advantages
      of the system are manifold, it also has certain drawbacks and limitations. The
      two-hybrid system has been shown to be extremely useful for placing a protein of
      unknown function within a functional context, thereby providing information about
      a putative role of the uncharacterised protein. This concept has also been
      successfully applied in molecular gerontology.

PMID- 12232525
TI  - [Program of the French college for vascular disease].

PMID- 12232526
TI  - [Inaugural address of the President. The children of Charles Dotter].

PMID- 12232527
TI  - [Address of the general secretary].

PMID- 12232528
TI  - [The astronauts of the European Space Agency].

PMID- 12232529
TI  - [Risk of hemorrhage with oral anticoagulants for deep vein thrombosis].
AB  - Despite standardized tests (PT-INR) and better definition of therapeutic
      objectives, oral anticoagulation still leads to a significant number of
      hemorrhagic events. The risk is higher during the initial phase of treatment and
      for arterial indications, but must also be considered for other situations,
      including deep vein thrombosis, where the risk is less well defined. This risk
      can now be quantified on the basis of recent data used to identify at risk
      populations. The risk scores account for age, gender, associated cancer, weight,
      history of digestive tract bleeding or stroke, and comorbidity (recent myocardial
      infarction, hematocrit<30%, serum creatinine > 15 mg/l, diabetes). A high score
      is associated with higher risk of hemorrhagic events. Besides the patient's
      clinical status, the risk of hemorrhage is related to compliance, the level of
      anticoagulation, and drug interactions. Specialized monitoring centers provide a
      means of reducing the risk of morbidity and mortality. New anticoagulation agents
      must be developed to reduce the risk of hemorrhage which remains an important
      cause of morbidity and mortality, particularly in the elderly and patients at
      risk.

PMID- 12232530
TI  - [Ionizing radiation and hyperplasia of the intimal matrix: current data and
      perspectives].
AB  - Vascular reconstruction (bypasses or endoluminal procedures) is still associated
      with a significant rate of restenosis. For restenosis, smooth muscular cells are
      the principal actor by their property to migrate, proliferate and secrete extra
      cellular substance after their change of phenotype. A variety of pharmacological
      and mechanical strategies have been directed with limited success. Using ionizing
      radiation have been recently developed, aiming to reduce the cell proliferation
      and consecutive restenosis following vessel injury (anastomoses or angioplasty).
      We reviewed the use of radiations on animals, cellular action and recent clinical
      trials. Recent clinical trials confirm an effective action of using radiations
      for restenosis prevention. We reviewed methods of delivering radiations also
      drawback and consequences using these hopefully methods.

PMID- 12232531
TI  - [Fibrinogen: factor and marker of cardiovascular risk].
AB  - Most cardiovascular events result from a thrombotic complication in patients with
      atherosclerosis. Inflammation plays a central role both in the pathogenesis of
      atherosclerosis and in the development of complications (particularly plaque
      rupture). Fibrinogen is both a marker of inflammation and a major determinant of
      thrombosis and hemorrheology. Clinical data corroborate with epidemiological data
      showing that higher serum fibrinogen level (compared with matched controls) is
      predictive of both the risk of primary cardiovascular events in the general
      population and the risk of secondary events among patients. Fibrinogen level,
      determined by both environmental and genetic factors, is a good example of gene
      environment interaction. The rise in fibrinogen level indicative of significantly
      increased risk is actually very small, lying within the normal range. This
      explains why epidemiological data cannot be used to establish cardiovascular risk
      for individual patients in routine practice (excepting very high elevations
      rarely encountered). To date, fibrinogen is the only compound formally recognized
      as both a risk factor and a marker of cardiovascular risk. Other compounds,
      including CRP, von Willebrand factor, and more recently the CD40-CD40 ligand
      system, have also been shown to play a double role as predictors and markers.
      These new developments shed new light on fibrinogen as a risk marker/factor for
      atherothrombotic ischemic events.

PMID- 12232532
TI  - [Local care and medical treatment for ischemic diabetic ulcers].
AB  - Optimal medical treatment of ischemic diabetic ulcers is multifactorial.
      Infection is very common and it is necessary to distinguish between limb or life
      threatening infections and non-limb-threatening infections. The major pathogen
      associated with non-limb-threatening infection is staphylococcus aureus; oral
      antibiotics such as amoxicillin/clavulanate or clindamycin can be used. For
      severe infection, empiric antibiotic therapy is broader-spectrum covering
      staphylococci, streptococci, gram-negative bacilli and enterococci; intravenous
      administration is the rule. Duration of antibiotic therapy depends on severity
      and depth of infection, and on requirement of surgical debridment. Granulocyte
      colony-stimulating factor is a growth factor stimulating proliferation and
      function of neutrophils. As an adjunctive therapy for limb-threatening
      infections, it is associated with a lower rate of amputation. Increasing arterial
      perfusion if the patient is unsuitable for reconstructive surgery or angioplasty
      is desirable. Iloprost is an analogue of epoprostenol with effects on platelet
      aggregability and vasodilatation. It improves ulcer healing, decreases pain,
      slightly diminishes the rate of amputation. Systemic hyperbaric oxygen therapy
      can perhaps improve clinical outcome but additional research is needed to define
      the specific indications and benefits of this treatment modality. Local care is
      not rationalized and depends on local habits. Debridment is required. Non
      necrotic wounds can be covered by modern dressing (hydrophilic dressing,
      alginates, hydrocolloid). Necrotic wounds are dryed until surgical
      revascularization, or excised if they are limited and superficial. Pinch grafts
      are very useful for arterial ulcers. The place of topical growth factor like PDGF
      (platelet derived growth factor) and of living skin equivalents (dermagraft,
      apligraf) is not defined in ischaemic diabetic ulcers. Treatment of edema is
      necessary, because it retards or complicates healing. Inelastic bandages can be
      useful with good tolerance if ischemia is not critical. Pneumatic foot
      compression is under evaluation. Electric stimulation could be an adjuncting
      treatment, but with a problem of compliance. Reducing plantar pressure is always
      necessary.

PMID- 12232533
TI  - [Anterior jugular-internal jugular bypass to salvage a dialysis arteriovenous
      fistula].
AB  - Thrombosis of the anonymous vein can compromise the arteriovenous fistula in
      chronic renal patients on hemodialysis. Clinical manifestations include edema of
      the arm, stasis acrocyanosis, tugor of the neck and shoulder veins, and severe
      headache. The fistula may have to be closed to achieve symptom relief, requiring
      a catheter for dialysis until an new arteriovenous fistula becomes functional. In
      case of stenosis or occlusion of the brachiocephalic venous axis, the goal is to
      preserve a functional fistula yet resolve symptoms. Self-expanding stents have
      been used but results have been less than satisfactory or short-lived. Different
      surgical bypass techniques have been proposed. We report an anterior jugular
      internal jugular bypass used to salvage a dialysis arteriovenous fistula.

PMID- 12232534
TI  - [Spinal ischemia after biiliac aneurysm surgery related to Behcet's disease
      diagnosed two years later].
AB  - A 26-year-old woman underwent bypass surgery for biiliac aneurysm of unknown
      origin. The aorta was cross clamped below the renal arteries to insert a tube
      graft between the infra-renal aorta and the external iliac arteries with
      implantation of the internal iliac arteries on the prosthesis. Due to leakage
      from the posterior area of the proximal anastomosis, the proximal suture was
      redone. Total cross clamping lasted 65 minutes. No blood pressure drop was noted
      during or after the procedure. Postoperatively, the neurological examination
      revealed paraplegia with mild sensorial deficit and fecal and urinary
      incontinence. The fecal and urinary deficit resolved three months later. Nearly
      complete motor recovery was noted at the 18(th) postoperative month. The patient
      then presented oral and genital ulceration at 22 months postop leading to the
      diagnosis of Behcet's disease. Several risk factors have been suggested to
      explain spinal ischemia after abnormal aortic surgery: anatomic variablility of
      spinal perfusion, duration of aortic cross clamping, and intra- or postoperative
      episodes of hypotension. Thrombotic damage to the arterial system due to Behcet's
      disease could also perturb spinal blood supply and reproduce one of the
      mechanisms incriminated in ischemic spinal lesions occurring during aortic
      surgery for atheromatous aneurysm.

PMID- 12232535
TI  - [Lymphangioma in a patient with Maffuci syndrome of the lower legs].
AB  - Maffucci syndrome is a rare dysembryoplasia associating cartilage tumors similar
      to enchondromas in Ollier's disease and vessel tumors. We report the case of a 50
      year-old woman with Maffucci syndrome involving the lower legs who developed a
      variety of vascular proliferations. This patient had capillary hemangiomas,
      cavernous angiomas, and lymphangiomas facing the cartilage tumefactions on the
      thigh. Regular clinical surveillance is required for such patients due to the
      risk of degeneration of the enchondromas and the angiomas, but also due to the
      possible occurrence of other malignant tumors besides the cartilage and vessel
      tumors.

PMID- 12232536
TI  - [Factorial analysis and internal consistency of the French version of the Toronto
      Alexithymia Scale (TAS 20), in obese women].
AB  - The term alexithymia is derived from the Greek and means no words for feeling and
      is used to describe a personality trait characterized by the inability to
      experience and express emotion. Alexithymia is a relevant feature in subjects
      with eating disorders. The Toronto Alexithymia Scale (TAS) is the more used scale
      to assess alexithymia. The TAS 20 represents the latest revised and short version
      of the TAS, with psychometric properties clearly superior to the other
      alexithymia scales. The TAS 20 is a 20-items self-administered questionnaire
      including three subscales: ability to identify feelings, ability to describe
      feelings and externally oriented thinking. The TAS 20 was sparsely used in obese
      people and its validity was not studied at the present time in this specific
      population. The aim of this study was to assess the internal consistency and the
      factorial structure of the TAS 20 in a group of obese women. Method-The TAS 20
      was administered to 192 obese women willing to loose weight, aged from 18 to 60
      years. Their body mass index (BMI) was ranged from 27.5 to 55,0 kg/m2. The
      patients also completed a depression scale (Beck Depression Inventory 13).
      Cronbach's alpha coefficient was used to investigate the internal consistency of
      the scale. A confirmatory factorial analysis was performed to examine the
      validity of the initial three-factor structure in this population. The
      confirmatory factor analysis was conducted using STATISTICA 5.0((R)). Results-An
      exploratory factorial analysis using the principal components method was
      performed to search for a more relevant factorial structure. The global internal
      consistency value (a) was 0,74 for the full scale. The a coefficients were 0.78
      and 0.67 respectively, for the two first subscales, (ability to identify feelings
      and ability to describe feelings), but was low (a=0.33) for the last subscale
      (externally oriented thinking). This result questionned the initial three-factor
      solution and conducted us to perform a exploratory factorial analysis. This
      analysis yielded a six factors solution, explaining 58.7% of the total variance,
      with the sole item 3 forming the sixth factor. The factor analysis yielding a
      five factors solution was retained. This solution explained 53.6% of the total
      variance. The first factor (22.3% of the variance) was constituted by the
      majority of the first subscale's items (items 1, 3, 6, 7, 9, 11, 13, 14) and
      corresponded to the ability to identify feelings. Four items out of five of the
      second dimension ability to describe feelings (items 2, 4, 12, 17) constituted
      the fourth factor (7.1% of the variance) of the analysis. The third subscale
      (externally oriented thinking) was divided in three factors explaining
      respectively 10.7%, 7.5% and 6.0% of the variance. The first of them included the
      items 5, 10 and 18, the second one included the items 15, 16 and 20, and the last
      one included the items 8 and 19. We called these three factors emotional
      avoidance , lack of interest in psychological comprehension and cognitive
      avoidance , respectively. The parameter estimates of the confirmatory factorial
      analysis for this five-factor solution were: c(2) goodness-of-fit=287.50 (df=141;
      p<0.001), goodness-of-fit-index=0.87, adjusted goodness-of-fit index=0.82, root
      mean-square-residual=0.08. The different models were compared by testing the
      differences in the chi-squares. The five-factor solution was better than the
      other tested models. Discussion-The results of the present study indicate that
      the use of the TAS 20 to assess alexithymia in obese subjects willing to loose
      weight, requires a careful interpretation related to the features of this
      population. Exploratory factorial analysis suggests a five factors solution
      statistically and clinically more relevant than the three factors solution. The
      first dimension (ability to identify feelings) is retained. The second dimension
      (ability to describe feelings) could rather be linked to the common wishes of
      obese women to keep their own feelings to themselves than to a dimension of
      alexithymia. Our data suggest to t to divide the last initial dimension
      externally oriented thinking in three independant factors which we named:
      emotional avoidance , cognitive avoidance and lack of interest in psychological
      comprehension . Emotional and cognitive avoidance could be linked to the fact
      that our subjects wanted to loose weight and exhibited restrain eating. A
      positive correlation between restrain eating and alexithymia was previously
      reported. The last factor lack of interest in psychological comprehension would
      constitute an actual dimension of alexithymia: former studies found a negative
      correlation between alexithymia and psychologically oriented thinking.

PMID- 12232537
TI  - [Bipolarity correlated factors in major depression: about 155 Tunisian
      inpatients].
AB  - The distinction between the depressive troubles according to their inclusion in
      bipolar disorders or in recurrent depressive disorders offers an evident
      practical interest. In fact, the curative and mainly the preventive treatment of
      these troubles are different. So it is necessary to identify the predictive
      factors of bipolar development in case of inaugural depressive episode. In 1983,
      Akiskal was the first who identified those factors: pharmacological hypomania,
      puerperal depression, onset at early age (<25 years), presence of psychotic
      characteristics, hypersomnia and psychomotor inhibition. Through this study, the
      authors try to compare the epidemiological, clinical and evolution
      characteristics of major depression in bipolar disorders to recurrent depressive
      disorders in order to indicate the correlated factors with bipolarity. It is a
      retrospective and comparative study based on about 155 inpatients for major
      depressive episode during the period between January 1994 and December 1998.
      These patients were divided into two groups according the DSM IV criteria:
      bipolar group (96 patients) and recurrent depressive group (59 patients). Both
      groups were compared according to socio-demographic data, life events in
      childhood, personal and family history, clinical and evolution characteristics of
      the index depressive episode. The predictive factors proposed by Akiskal were
      systematically examined. It was found out that the following factors were
      correlated with bipolarity: high rate of separation and divorce (17.7% versus
      5.1%; p=0.02), family history of psychiatric disorders (56.3% versus 35.6%;
      p=0.012) especially bipolar ones (29.2% versus 3.4%; p=0,00008), onset at early
      age (mean age of onset: 24.8 8.2 years versus 34.1 12.6 years; p=0.000004),
      number of affective episode significantly more frequent (mean 3.6 versus 2.5;
      p=0.03), sudden onset of depressive episode (44.8% versus 15.9%; p=0.0003) and
      presence of psychotic characteristics (69.8% versus 16.7%; p=0.0001) catatonic
      characteristics (37.3% versus 20.3%; p=0.03), hypersomnia (51% versus 20.3%;
      p=0.03) and psychomotor inhibition (83.3% versus 42.4%; p=0.00007). Negatively
      correlated factors of bipolar depression were: somatic comorbidity such as
      diabetes, hypertension and rhumatismal diseases (12.5% versus 28.8%; p=0.012) and
      association with dysthymic disorders (2.2% versus 12.1%; p=0.029). No correlation
      was found between bipolarity and life events in childhood, seasonal character,
      alcoholic dependence and suicide attempt. Concerning the validity of predictive
      factors of bipolarity proposed by Akiskal, we found: history of bipolar disorders
      (Sensibility: 29.2%, specificity: 96.6%, Positive Predictive Value (PPV): 93%),
      hypersomnia (Sensibility: 51%, specificity: 80%, PPV: 80%), onset before the age
      of 25 years (Sensibility: 62.5%, specificity: 70%, PPV: 77%), psychomotor
      inhibition (Sensibility: 83.3%, specificity 58%, PPV: 76%), and psychotic
      characteristics (Sensibility: 69.8%, specificity: 62.7%, PPV: 75%). In spite of
      methodological differences, our results tallied with the other studies. We focus
      on the importance of the bipolar family history criterion, which has the highest
      PPV, and the limits of psychotic characteristics criterion which has the lowest
      PPV. This may be explained by the frequency of these characteristics of affective
      disorders in our cultural context. The association of the hypersomnia and
      psychomotor inhibition in one criterion in order to increase their diagnostic
      power. Our study helps us to identify the factors that would predict the bipolar
      evolution of a depressive episode allowing the use of specific treatment and
      ensuring the improvement of prognostic.

PMID- 12232538
TI  - [Influence of attention on an auditory-verbal learning test in schizophrenic
      patients].
AB  - Schizophrenic patients are known to feature alterations in their cognitive
      performances, principally in executive functions, attention and memory. In this
      last domain, studies have shown a relatively severe and global deficit, which can
      be assessed in chronic and first episode patients. It seems that the memory
      dysfunction is independent of age and intellectual level, but does correlate with
      negative psychopathology and global functioning. In the study of memory
      dysfunction, attentional capacities, information processing and symptomatology
      have to be considered as determining factors. It has been shown that patients
      with schizophrenia perform poorly in selective attention tasks and that this
      deficit may interfere with learning. In the same way, the slowing of information
      processing contributes to a superficial and incomplete learning. The impact of
      symptomatology has also to be considered, as negative and depressive symptoms are
      linked to mnesic performances. The majority of studies bearing on working memory
      and schizophrenia show an alteration of performances, but studies on long term
      memory are more equivocal. Procedural memory seems to be preserved, while
      declarative memory is impaired. These results support the hypothesis that in
      schizophrenia, memory processes that are consciously controlled are impaired,
      contrary to implicit learning which may be intact. Nevertheless, studies bearing
      on semantic memory and episodic memory show controversial results. Still, many
      authors argue that schizophrenic patients have difficulties in recalling learned
      material, specially when a delay or a interfering task are introduced in the
      test. Besides, the schizophrenic subjects do not use the semantic properties of
      the words, as well as the control subjects, when they have to learn a words list
      for example. The main goal of the present study was to examine the auditory
      verbal learning capacities of 31 schizophrenic patients (20 men and 11 women, 19
      56 years old), compared to 27 healthy subjects (11 men and 16 women, 23-56 years
      old). All subjects received an evaluation including the Rey Auditory-Verbal
      Learning Test, used to study the progressive acquisition of 15 disyllabic words
      which are successively orally presented five times to the subject. About forty
      five minutes after the last of the five immediate recalls, the delayed recall is
      assessed and a percentage of retention is also calculated. Visual reasoning and
      attention capacities were studied with the Progressive Matrix and the d2
      encumbrance test respectively. Global psychiatric symptomatology of the patients
      group was assessed with the Brief Psychiatric Rating Scale. Considering the
      literature existing on the verbal learning capacities of schizophrenic patients,
      it was expected that the patients would perform poorly and learn slower than
      controls. The initial learning of the material, which is a critical stage for
      schizophrenic patients, was studied with particular attention as well as the
      effect of the introduction of a delay upon the recall of the words list. A
      secondary objective of the study was to investigate the role of visual reasoning
      and attention upon auditory-verbal learning process. According to published
      studies, it is expected that schizophrenic patients manifest some impairment in
      the domains of visual reasoning and attention. The question is to know whether it
      alters performances in the auditory-verbal learning test or not. Finally, the
      links between clinical characteristics of the patients, like age and illness
      duration, and their learning performances were explored. Statistical analysis
      included first a descriptive analysis of data to examine differences between the
      two groups. Second, ANCOVAs were used in order to control the respective impact
      of educational level, attention capacities and verbal reasoning capacities upon
      learning performances. Third, Spearman's correlations were used to detect links
      between clinical characteristics of the patients and learning performances. The
      comparisons between patients and controls confirmed that schizophrenic patients
      scored less in the attentional and visual reasoning tasks. They also featured a
      lower educational level compared to the healthy subjects. In the auditory-verbal
      learning test, the patients showed altered performances in the five recalls, as
      well as in the delayed recall and for the retention percentage. In order to
      control the impact of educational level, attentional and visual reasoning
      capacities, these parameters were introduced in the statistical analyses.
      Educational level did not influence memory alterations in the schizophrenic
      group. However, attention and, to a lesser extend, visual reasoning had an impact
      on the comparison of memory scores: when controlling attention, almost no
      significant group effect remained. Finally, the exploratory analyses of links
      between clinical characteristics and memory only revealed the presence of a
      significant negative correlation between illness duration and learning
      performances. Thus, the analyze of data showed that schizophrenic subjects
      featured poor performances in the domains of attention, verbal reasoning and
      auditory-verbal memory. Further analyses taking into account group differences on
      attention suggest that the impairment featured by schizophrenic patients in the
      domain of verbal memory strongly relies on an attentional deficit. These results
      are discussed according to the existing literature and methodological
      limitations. Clinical implications are also discussed.

PMID- 12232539
TI  - [Study of psychometric properties of two new questionnaires assessing beliefs in
      hypochondriasis in a non-clinical population].
AB  - Most instruments focussing on hypochondriasis symptoms do not have for goal to
      assess beliefs specifically. Instead, these instruments are used to measure
      specific behaviors. To assess underlying beliefs with these kinds of instruments,
      you have to extract false beliefs by deduction. In cognitive therapy, it is
      important to target erroneous beliefs in order to change them. On the other hand,
      existing instruments are not really suitable to target erroneous health beliefs.
      Even if some questionnaires are built to assess beliefs directly, it seems that
      they only measure the conviction of having an illness and do not assess the
      general health beliefs present in excessive health worriers. However, many
      researchers argue that this other kind of beliefs are the ones responsible in
      maintaining hypochondriasis symptoms. Presently, researchers assume that
      erroneous beliefs can maintain worries about illness among people with
      hypochondriasis symptoms like false beliefs about worry maintain worries in
      people with General Anxiety Disorder (GAD). Even if the importance of false
      beliefs in the maintenance of pathological worries is now recognized, most
      instruments on hypochondriasis symptoms do not have for goal to assess erroneous
      beliefs concerning worry about health. For instance, although the questionnaire
      Why do people worry? (WW) shows good psychometric properties and measures beliefs
      related to general worries, this questionnaire is not specific enough to
      correctly evaluate beliefs associated to health worry. A new questionnaire has to
      emerge in order to assess false beliefs associated to worry about health. This
      manuscript presents the development and the validation of a new questionnaire:
      the General Health Beliefs Questionnaire (GHBQ) that assesses general health
      beliefs, and also presents the development and the validation of a new
      questionnaire assessing beliefs associated to worry about health: the Why do
      people Worry about Health? (WW-H) . In this study, the GHBQ's and the WW-H's
      psychometric qualities and the factorial structure were assessed. More precisely,
      this study examined the factorial structure, the temporal stability, the
      convergent, divergent and criteria validities of the GHBQ and the WW-H. Four
      hundred and twenty nine French-speaking university students (non-clinical
      participants) completed a battery of questionnaires at the beginning of a class.
      The questionnaires were: The General Health Beliefs Questionnaire (GHBQ), the Why
      do people Worry about Health (WW-H), the Illness Worry Scale (IWS), the Beck
      Depression Inventory-short form (BDI-short form) and the Beck Anxiety Inventory
      (BAI). A second administration took place three weeks later with the same sample
      to test the temporal stability of the GHBQ and the WW-H. The principal component
      analysis with orthogonal rotation (varimax) supports a five components solution
      for the GHBQ: 1) magical thinking, 2) health, 3) consequences, 4) responsibility,
      and 5) vulnerability. The principal component analysis with oblique rotation
      (direct oblimin) (d=0) found a two components solution for the WW-H: 1) utility
      and 2) magical thinking associated to worries about health. The internal
      consistency of the GHBQ and the WW-H is excellent (a=.80 and a=.90,
      respectively). A correlation of 0.49 was found between the GHBQ and the WW-H. The
      correlation between the GHBQ and the IWS who evaluates the tendency to worry
      (r=.50) and between the WW-H and the IWS (r=.49) showed that the convergent
      validity of these questionnaires is adequate. On a three weeks interval, the GHBQ
      (r=.70) and the WW-H (r=.71) showed a satisfying temporal stability. The means of
      the high worriers (80 superior percentile at the IWS) (M=38.8, ET=8.93) and the
      means of the moderate worriers (between the 40 and the 60 percentile at the IWS)
      (M=32.8, ET=8.00) on the GHBQ have been compared. A significant difference has
      been found between the two groups [F(1,181)=23,129, p<0,001]. Also, the means of
      the high worriers (M=27.3, ET=8.59) and the means of the moderate worriers
      (M=23.8, ET=8.56) on the WW-H haveave been compared. An ANOVA has found a
      significant difference between these two groups [F(1,180)=7,396, p=0,007]. These
      results show that general health beliefs and false beliefs associated to worry
      about health are more often present in high worriers than in moderate worriers.
      The GHBQ and the WW-H allow psychologists, physicians and psychiatrists to do a
      quicker and more exhaustive evaluation of general health beliefs and false
      beliefs associated to worry about health, in less costs. These questionnaires
      will improve the chances of success of the hypochondriasis' treatment by helping
      clinicians to detect and correct false beliefs more easily.

PMID- 12232540
TI  - [French validation study of the levels of emotional awareness scale].
AB  - According to a thesis based on the idea of an influence of cognitions in the
      structuring of internal reality, emotional awareness, ie the capacity of
      representing your own emotional experience and that of others, is a cognitive
      process that goes into maturation. Defining this concept, Lane and Schwartz
      present a cognitivo-developmental model in five stages of the processes of
      symbolization, accounting for the differences in levels of emotional awareness
      observed in individuals. The organization of these cognitive processes would thus
      be structured in well differentiated stages, in which the development of the
      emotions would be inseparable from the development of ego and of the relation to
      others. These authors focus on the capacity of representing in a conscious way
      the emotional experience and consider that verbal representations used to
      describe the contents of what is experience constitute a good reflection of the
      organization structural of the emotional awareness. Therefore, they worked out an
      instrument of evaluation: the Levels of Emotional Awareness Scale (LEAS), which
      measures the capacity to describe your own emotional experience and the one you
      allow to others, in an emotional situation. The system of quotation of this scale
      is based on the analysis of the verbal contents of the provided answers, in
      direct reference to the authors' theory of the levels of differentiation and
      integration of the emotional experience. It is therefore an empirical measurement
      which is centered specifically on the structural organization of the emotional
      experience. The various studies of validation of this instrument show that it
      presents solid metrological properties. This work presents the validation of the
      French version of Lane and Schwartz's LEAS. Validity and fidelity were studied in
      a group of 121 healthy subjects. This setting is part of a larger clinical
      evaluation, also including a collection of socio-demographic and clinical data,
      and other instruments of self-evaluation (Beck Depression Inventory, BDI,
      Hospital Anxiety and Depression Scale, HAD, and Toronto Alexithymia Scale, TAS).
      The face validity appears correct: the questionnaire was well accepted and seemed
      easy to complete. A principal components analysis of the correlation matrix of
      the set of items was used as the method of extraction of the various factors and
      made it possible to confirm the unidimensionality of the instrument. The number
      of factors to be retained was given according to Kaiser and Cattell criteria. The
      internal consistency was evaluated through computation of the Cronbach
      coefficient, whose value is 0.75 for the scale's global score. The confidence
      interval of the margin of error of LEAS scores was also measured; for the global
      score it is IC=[m 6.1]. The measure given by this rating scale may therefore be
      considered sufficiently accurate, since this interval is weak. A study of the
      frequency of quotation of each item of the instrument was carried out, in order
      to check the homogeneity and the uniformity of quotations, as well as a diagram
      of distribution of the score, showing that it follows a law which is close to a
      normal law. The concurrent validity could only be studied via the similar concept
      of alexithymia, measured with the TAS, for there is not other instrument
      validated in French evaluating the levels of emotional awareness, and these two
      instruments seem to measure different notions, because none of the correlations
      between the scores of these two questionnaires are significant. Concerning
      discriminant validity, the Pearson correlation coefficients between the global
      score for the LEAS, the BDI score and the HAD sub-scores for  depression  and 
      anxiety  were measured; it is clear that the level of emotional awareness is
      independent from negative affects. Furthermore, the study of the reliability made
      it possible to highlight excellent intra-class correlation coefficients
      (r=0.993). The French version of the Levels of Emotional Awareness Scale thus
      appears to be valid and accurate and should allow the study of levels of
      emotional awareness on psychopathology. It is about an easily acceptable and
      simple questionnaire of use in varied clinical circumstances.

PMID- 12232541
TI  - [Inferiority in normal and anxious populations].
AB  - BACKGROUND: The construct of inferiority can be defined as an intimate,
      unrealistic and persistent conviction to be always low-ranking in merit, value,
      intellectual and/or physical capacities (Weiner et Mohl, 1996; Yao et al., 1996).
      This can be considered as an important cognitive factor in anxiety disorders.
      But, does a feeling of inferiority also exist in normal subjects? We hypothesized
      that the feeling of inferiority might be a normal phenomenon if it is a transient
      experience, in relation to external events, and represents an aspect of self
      esteem. The Inferiority Scale (Yao et al., 1998), aimed at measuring the feeling
      of inferiority in anxiety, is a self-report instrument including 17 items
      assessing self-appraisal of inferiority and 17 items assessing inferiority linked
      to others' judgements. It showed good psychometric properties of reliability and
      validity in previous studies. The aim of our study was to confirm the existence
      of inferiority feeling in non-clinical subjects, and its continuity between
      normal and anxious populations. Method - We included 264 non-clinical subjects in
      the study. The mean age of the sample was 30.38 years old (SD=10.25) and 36% (94
      Ss) were men. The anxious population was composed with 57 subjects suffering from
      obsessive compulsive disorder (OCD) and 43 patients with social phobia according
      to DSM IV. The mean age of this population was 34.0 years old (SD=10.6) and 51%
      of them were men. The Inferiority Scale was used in our study for evaluating the
      feeling of inferiority. RESULTS: Most of non-clinical subjects reported low
      inferiority feelings and a part of the non-clinical subjects (15%) presented a
      moderate or strong feeling of inferiority, on the Inferiority Scale. The non
      clinical subjects group was divided into two sub-groups (Low and High
      Inferiority) with the median of the Inferiority Scale total score. The total
      score and the sub-scores of the Inferiority Scale were all significantly higher
      in the two anxiety groups than in the two non-clinical sub-groups (p<0.0001) and
      higher in non-clinical subjects with high inferiority, compared to those with low
      inferiority (p<0.0001). Noting that the social phobic group presented higher
      scores of the Inferiority Scale than the OCD group (p=0.0058). There was a
      significant and negative correlation between age and the Inferiority Scale in non
      clinical subjects, but there was no between-sex difference on the scale.
      CONCLUSION: Our results confirm the existence of inferiority feeling in non
      clinical subjects and suggest the existence of continuity of inferiority feeling
      as a psychological trait between normal and pathological populations.

PMID- 12232542
TI  - [Use of atypical antipsychotics in Charles Perrens psychiatric hospital
      (Bordeaux) analysis of prescribing practices for Amisulpride, Clozapine,
      Olanzapine and Risperidone].
AB  - The commercial introduction of atypical antipsychotics (AAP) constitutes a
      considerable step forward in the sense that it has led to a world-wide
      reappraisal of the established treatment strategies for people with psychoses
      (including schizophrenia and affective psychoses). They have allowed refinements
      in the pharmacologic management of psychoses but they have a higher acquisition
      cost than conventional neuroleptics. The cost of the newer AAP had a substantial
      effect on medical resources: the AAP account for only 43.2% of neuroleptic
      prescriptions, but 76.1% of medical costs associated with neuroleptic drugs, and
      in terms of treatment costs, a reduction (50%) was found with risperidone
      compared with olanzapine for a same number of treated patients. The aim of this
      paper was to examine the use of these drugs, to compare them and to assess their
      impact within the context of psychiatric hospital practice, by means of analysis
      of prescribing practices for amisulpride, clozapine, olanzapine and risperidone
      for all treated patients. We conducted an observational, naturalistic study at
      Charles Perrens psychiatric Hospital in Bordeaux (France) that reproduced the
      clinical conditions in which these new drugs are used. Four photographies of all
      the medical prescriptions concerning atypical antipsychotic drugs were done
      between October 1999 (four months after the introduction in France of the
      olanzapine, the last of the new antipsychotics) and June 2001 (n=682
      prescriptions). The total amount of these prescriptions corresponded to 527
      patients. Treatment groups were compared - first overall and after by considering
      2 groups: psychotic and non-psychotic patients - through descriptive analyses of
      sociodemographic characteristics of patients, diagnosis, percentages of patients
      receiving concomitant psychotropic medication and/or receiving treatment-emergent
      side effects and mean dosages of AAP therapy according to concomitant medication.
      In the same way, we compared the four AAP through their prescribing
      practices'evolution during the four survey. RESULTS: AAP drugs account for 43.2%
      of prescriptions (and conventional neuroleptics 56.8% of them). We recorded a
      significant increase between the four surveys (p<0.02): 36.6% at the beginning to
      47.8% at the end of the study. From the 682 collected prescriptions, 72 (10.6%)
      included clozapine, 130 (19.1%) amisulpride, 229 (33.6%) olanzapine and 251
      (36.8%) risperidone. Sixty five percent of AAP prescriptions involved psychotic
      patients. A relative stability in characteristics of AAP prescriptions during the
      four surveys was found. So, no significant differences were observed between
      amisulpride, olanzapine, risperidone, in terms of age, sex, sociodemographic
      characteristics, unlike clozapine. However, there were statistical differences
      between all the AAP in the concurrent use of other neuroleptic agents (p<0.02),
      hypnotic drugs (p<0.006), mood stabilizer drugs (p<0.03), and anticholinergic
      drugs (p<0.007). Statistically, the mean dosage of amisulpride increased when a
      mood stabilizer drug was coprescribed (p<0.0007), but it decreased with an
      antidepressant drug (p<0.004) or an hypnotic drug (p<0.02); clozapine 's one
      decreased every time an antidepressant drug was coprescribed (p<0.02); with
      olanzapine, there was a significant increase every time an other neuroleptic
      agent (p<0.03) or an anticholinergic drug (p<0.006) was associated; then for
      risperidone, the mean dosage increased with the coprescription of an other
      neuroleptic agent (p<0.00002), an anticholinergic (p<0.00003) or an adrenolytic
      drug (p<0.04). The pattern of prescribing practices that emerges from our four
      surveys suggests that these new AAP are significantly more and more often
      associated with a stabilizer mood drug (p<0.009) (particularly the olanzapine)
      or/and an anxiolytic drug (p<0.05) (like the amisulpride in particular).
      Considering the four AAP globally, but more with the risperidone, the association
      with a neurovegetative corrector agent decreased (p<0.004) during the four
      surveys. Then, concerning the psychoticng the four surveys. Then, concerning the
      psychotic patients, the AAP were significantly more often associated with other
      neuroleptic agents (p<0.03), the amisulpride in particular, with anticholinergic
      drugs (p<0.00005), but significantly less with mood stabilizer drugs (p<0.00003)
      principally the amisulpride and the risperidone, with antidepressant drugs
      (p<0.02) particularly the risperidone. This kind of survey, however it is too
      much rare, is very important because it shows the clinical conditions in which
      these new drugs are really used. The results show that AAP appear to be the
      replacements of the older neuroleptics used in the treatment of psychoses,
      including particularly schizophrenia, but also in the treatment of mood
      disorders, and they reflect actual clinical practices. Other surveys must be
      achieved to see if our study confirms the general trend concerning the use of
      these drugs and so as to reassess these prescribing practices.

PMID- 12232543
TI  - [Efficacy and acceptability of tianeptine and sertraline in the acute treatment
      phase of depression].
AB  - Efficacy and acceptability of tianeptine were investigated in a multicenter,
      randomized, double blind, and sertraline-controlled study. As a total, 212 in- or
      outpatients with DSM IV major depression single episode, recurrent and bipolar
      depression, were treated for 42 days either with tianeptine (37.5 mg) or with
      sertraline (50 mg). At inclusion, sociodemographic, physical and psychological
      parameters showed no significant intergroup differences. MADRS responders (50%
      reduction of baseline score) were 66% and 67% with tianeptine and sertraline,
      respectively. No statistical interdrug differences were observed either in the
      number of withdrawals or in the efficacy and acceptability parameters.

PMID- 12232544
TI  - [Second generation SSRIS: human monoamine transporter binding profile of
      escitalopram and R-fluoxetine].
AB  - BACKGROUND: Single isomers of the selective serotonin reuptake inhibitors
      citalopram (escitalopram, S-citalopram) and fluoxetine (R-fluoxetine) are
      currently under development for the treatment of depression and other psychiatric
      disorders. Previous studies conducted in laboratory animals have revealed that
      the biological effects on serotonin reuptake for citalopram reside in the S
      enantiomer. In contrast, both enantiomers of fluoxetine contribute to its
      biological activity. METHODS: In the present study, the potency and selectivity
      of escitalopram, R-fluoxetine, and all of the other currently available selective
      serotonine reuptake ihibitors were compared for binding affinity at the human
      serotonin, norepinephrine, and dopamine transporters and several select
      neurotransmitter receptors using radioligand binding assays. RESULTS: Both
      escitalopram and R-fluoxetine were potent inhibitors of the serotonin transporter
      (Ki=1,1 and 1,4 nmol/L, respectively). escitalopram was the most serotonin
      transporter-selective compound tested and was approximately 30 fold more potent
      than R-citalopram. CONCLUSIONS: As noted previously, paroxetine and sertraline
      possess moderate affinity (<50 nmol/L) for the human norepinephrine transporter
      and dopamine transporter, respectively. R-fluoxetine, unlike the other selective
      serotonin reuptake inhibitors, possesses moderate affinity (Ki=64 nmol/L) for the
      serotonin 2C receptor. Potential clinical correlates of these unique attributes
      of escitalopram and R-fluoxetine are discussed. (Biol Psychiatry 2001; 50: 345
      350 " 2001 Society of Biological Psychiatry).

PMID- 12232546
TI  - [Personality factors in depressive disorders: contribution of the psychobiologic
      model developed by Cloninger].
AB  - The psychobiological model of personality developed by Cloninger, including four
      dimensions of temperament and three dimensions of character, allows to explore
      personality factors associated with depressive disorders. The three main
      dimensions of temperament are Novelty Seeking (NS), ie the tendency towards
      excitement in response to novel or rewarding stimuli, Harm Avoidance (HA)
      hypothesized to represent the tendency to respond intensely to signals of adverse
      stimuli, and Reward Dependence reflecting the tendency to respond intensely to
      signals of reward and to maintain behavior previously associated with reward.
      These personality traits are hypothetically related to underlying
      neurotransmetter systems (especially NS to dopaminergic function and HA to
      serotonergic function). The two main dimensions of character are Self
      Directedness (SD) and Cooperativeness (C), measuring maturity traits respectively
      concerning individual and social adaptation; thus they are negatively correlated
      with the risk of personality disorder for a given patient. Many studies have been
      carried out with the Temperament and Character Inventory (TCI), or with the
      previous Tridimensional Personality Questionnaire (TPQ), in depressive disorders
      with cross-sectional but also with short-term and long-term longitudinal designs.
      They show primarily that patients with history of depressive disorders, even in
      euthymic phase, have very high Harm Avoidance scores. In prospective studies
      conducted in depressive patients, even after remission of the depressive
      episodes, the Harm Avoidance scores are lower than before treatment, but still
      elevated compared to the general population. The patients who fail to respond to
      antidepressant treatments have generally higher Harm Avoidance scores before
      treatment than the others. Overall, various results support four types of potent
      relationships between Harm Avoidance and depression: an influence of state on
      trait measure, a pathoplastic effect of Harm Avoidance on depressive expression,
      a vulnerability model (Harm Avoidance representing a susceptibility factor for
      depression), and a scar model with elevated Harm Avoidance scores even after
      remission of acute depressive symptoms. Other temperament dimensions, Novelty
      Seeking and Reward Dependence, are not consistently associated with depression
      characteristics nor affected by state effects, but Self-Directedness character
      dimension is often low when compared to subjects without depressive disorders,
      reflecting maladaptive personalities frequently associated to depressive
      disorders. Some studies suggest that low Self-Directedness scores can be
      predictive of suicidal behaviors. In cross-sectional studies, Harm Avoidance
      scores are highly positively correlated with depression intensity (r=0.23 to
      0.67) and Self-Directedness scores are highly negatively correlated with
      depression (r=- 0.37 to - 0.60). Some studies suggest that the temperamental
      dimensions assessed by the TCI could have a predictive value for the response to
      antidepressants treatments, but this result is controversial and needs further
      research. For example, a study conducted in 84 patients with major depressive
      disorder showed that temperament type based on TPQ traits explained 25% of the
      response to treatment variance: patients with high scores on both Harm Avoidance
      and Reward Dependence had a favourable response to either clomipramine or
      desipramine. Studies of the relationship of temperament dimensions to biological
      markers of depression have also been published. It has been shown for example
      that Reward Dependence and Harm Avoidance scores are significantly predictive of
      morning hypercortisolemia in depressed subjects. More specifically, correlations
      have been obtained between platelet serotonergic markers (5-HT2a receptors) and
      Harm Avoidance scores also in depressed patients. In conclusion, Harm Avoidance
      seems to be a vulnerability factor or at least an associated factor to depressive
      disorders. This temperament dimension is supposed to be highly heritable, and to
      be linked to the serotonergic system variations.

PMID- 12232545
TI  - [Pilot study comparing in blind the therapeutic effect of two doses of
      agomelatine, melatoninergic agonist and selective 5HT2C receptors antagonist, in
      the treatment of major depressive disorders].
AB  - Rational and method - Two doses of agomelatine (S-20098), a novel potential
      antidepressant drug with a new pharmacological profile (melatonin agonist and
      selective 5HT2C antagonist -MASSA), were compared in a double-blind, randomised,
      pilot study in order to estimate the antidepressant activity shown in preclinical
      data. Inpatients suffering from major depressive disorder (DSM III-R criteria)
      and presenting a minimal score of 25 for MADRS were selected at D -7. After one
      week of run-in placebo treatment, included patients received one evening dose of
      agomelatine (either 5 or 100 mg) for 4 to 8 weeks. Hospitalization was required
      at least for the first 3 weeks. Patients presenting a satisfying response to
      treatment (MADRS total score<15 or decrease 40% from inclusion score) could be
      treated as outpatients. A follow up of 2 weeks was performed after stopping the
      treatment. The total duration of the treatment period could vary, according to
      investigator's decision, between 7 and 11 weeks. Evaluation criteria included
      MADRS, HAMD-17, HAM-A, CGI and AMDP 5 at D0, D7, D14 and D28, and, when
      applicable, at D35, D42, D49 and D56. Safety evaluations included recording of
      adverse events, ECG monitoring and biology. Results - Thirty inpatients were
      selected and 28 included (14 per group). There was no major difference between
      groups at inclusion, neither for demographic nor evaluation criteria. One patient
      of each group was excluded of the ITT analysis; 19 patients completed the
      mandatory period up to D28: 10 in the 5 mg group and 9 in the 100 mg group; 10
      patients (5 in each group) carried on the study during the optional period, up to
      D56 for 7 out of them (4 in the 5 mg group, 3 in the 100 mg group). Efficacy
      criteria showed a significant improvement in both groups, with highly significant
      within group evolutions (p<0.001 whatever the criteria) and without significant
      difference between groups. However, better results were observed in the 5 mg
      group compared to the 100 mg group. Total MADRS scores then decreased from 30.7
      3.5 to 14.8 6.4 in the 5 mg group vs a decrease from 31.6 4.7 to 18.6 14.8 in the
      100 mg group. Furthermore, significant improvement between D14 and D28 visits
      were only seen in the 5 mg group. Analysis of somatic complaints (AMDP 5) showed
      with both treatment a strong decrease of symptoms during the study, especially
      for items related to sleep disorders (difficulties for falling asleep,
      interrupted sleep, shortened sleep, early wakening and drowsiness). Acceptability
      was good for both doses of agomelatine. However, there were slightly more
      emergent adverse events and severe treatment-related adverse event in the 100 mg
      group. No modifications of cardio-vascular parameters nor biological
      abnormalities were observed in both groups. Conclusion - Preliminary clinical
      data with agomelatine confirm the potential antidepressant effect in accordance
      with positive preclinical results. There was no significant difference between 5
      and 100 mg, both for efficacy and for safety. However, the data suggest that 5 mg
      could be a at least as effective and slightly better tolerated dose than 100 mg.
      Further double-blind controlled studies versus active comparators and placebo are
      required in order to confirm these results.

PMID- 12232547
TI  - [Anxiety and depressive disorders in tobacco dependence].
AB  - The association between tobacco dependence and various forms of anxiety and
      depressive disorders is well established. The presence of these disorders
      constitutes a key cause of failure in subjects seeking to stop smoking. In
      addition to the clinically manifest forms of such anomalies, systematic screening
      for minor forms of these disorders was performed at the Centre for Tobacco
      Studies of Creteil, France; as well as the standard questionnaire concerning
      personal and familial history and current psychological well-being, subjects were
      asked to complete two self-questionnaires, the HAD (Hospital Anxiety Depression
      score) and the BDI (Beck Depression Inventory, abridged version) together with
      the MINI (structured mini-interview). In a series of 400 heavy smokers, sub
      syndromes of such anxiety and depressive disorders were noted in 34% of subjects,
      and a combination of anxiety and depressive disorders was seen in 2/3 of these
      subjects, mainly general anxiety and social phobia, which were frequently
      preceded by depressive episodes. In these forms of tobacco dependence with
      anxiety and depressive disorder, relapse was very common in spite of nicotine
      substitution therapy (NST), usually as a result of a depressive episode that
      tended to subside very rapidly on resumption of cigarette smoking. Psychotropic
      therapy involving selective serotonin reuptake inhibitors (SSRIs) coupled with
      NST resulted in lasting success accompanied by an often unexpected and
      spectacular improvement in psychological status. These findings confirm the role
      of mood disorders in tobacco addiction in keeping with other types of addiction.

PMID- 12232548
TI  - Arteriovenous malformations in the basal ganglia region: Gamma Knife radiosurgery
      as first choice treatment in selected cases.
AB  - BACKGROUND: The authors report the results of Gamma Knife (GK) radiosurgery on a
      clinical series of selected patients with brain basal ganglia arteriovenous
      malformations (BG AVMs). Furthermore, clinico-epidemiological and anatomo
      functional pictures of BG AVMs and supratentorial cortical AVMs are comparatively
      analyzed, and their influence on the radiosurgical outcome is discussed. METHODS:
      At our Department, 33 BG AVMs (21 with FU >2 years) and 209 cortical AVMs (110
      with FU >2 years) with a radiosurgical volume 10 cc underwent GK from February
      1993 to July 2001. Mean age, male/female ratio (M/F), and bleeding rate at
      clinical onset in the 2 subgroups of patients were as follows: 25.5 years (5-62
      years), 16 M/17 F, and 30/33 (91%) in BG AVMs, respectively; 34.4 years (8-74
      years), 124 M/85 F, and 107/209 (51%) in cortical AVMs, respectively. Statistical
      analysis performed with contingency table method and deviance analysis according
      to generalized linear models showed that the differences concerning age at onset
      and bleeding rate were highly significant. RESULTS: The rates of complete
      obliteration, permanent morbidity, bleeding/rebleeding during latency period, and
      unsuccessful embolization attempt in the 2 subgroups of patients were as follows:
      81%, 4%, 8%, and 41.7% in BG AVMs, respectively; 85.5%, 2%, 2%, and 2% in
      cortical AVMs, respectively. CONCLUSIONS: In our experience, the different
      clinico-epidemiological and anatomo-functional characteristics between BG AVMs
      and cortical AVMs do not seem to influence the radiosurgical outcome as complete
      obliteration and permanent neurological sequelae rates are very similar in these
      2 subgroups of patients. GK radiosurgery may be considered the first choice
      treatment modality in BG AVMs with <10 cc volume (very high cure rate, very low
      permanent morbidity, and zero mortality). Although the haemorrhagic onset in BG
      AVMs is much more frequent than in cortical AVMs, the difference in the
      bleeding/rebleeding rate between the 2 subgroups of patients during the latency
      period is not statistically significant and this occurrence seems to be limited
      within the first year after GK.

PMID- 12232549
TI  - The role of constitutive nitric oxide synthase in pathogenesis of secondary
      lesion after spinal cord injury. Preliminary results.
AB  - BACKGROUND: Secondary lesion (SL) is an early phenomenon of cellular death
      following spinal cord injury (SCI). Nitric oxide (NO) could be involved in its
      pathogenesis. NO is a gaseous metabolite produced by 2 constitutive isoforms of
      NO synthase (cNOS), constantly active, and by 1 inducible isoform (iNOS),
      synthesized during inflammation and able to produce large amount of NO. High
      concentrated NO is toxic for cells; therefore, NO concentration is strictly and
      finely regulated. We suppose that major inhibitory effect on the iNOS expression
      is represented by the same physiological concentration of NO, synthesized by
      cNOS. The aim of this study is to assess the role of the 2 cNOS in pathogenesis
      of SL after SCI in rat. METHODS: A dorsal SCI has been performed on rats (n=5) by
      a vascular clip (50 g/mm(2) for 15"). Fifteen minutes after trauma, activity of
      nNOS and eNOS has been measured (U/mg) in the cervical, dorsal and lumbar
      segments of spinal cord. Uninjured rats (n=5) served as control group. m-RNA for
      iNOS in untreated rats (n=2) has been also investigated by Northern blotting.
      RESULTS: In injured rats nNOS activity has shown a reduction in dorsal and lumbar
      segments, compared to the control group. eNOS activity, highly variable in the
      control group, has not been detectable in injured spinal cord. i-NOS mRNA has not
      been found in spinal cord of uninjured rats. CONCLUSIONS: These results would be
      in line with our hypothesis and provide the bases for other investigations. New
      therapeutic strategies for SL prevention, based on the modulation of cNOS, will
      be evaluated.

PMID- 12232550
TI  - Surgical approaches to tumours of the lateral ventricles in the dominant
      hemisphere.
AB  - BACKGROUND: Intraventricular neoplasms are rare tumours (1% of the tumours of the
      central nervous system). The surgical approach sometimes is quite difficult,
      particularly in the dominant hemisphere. The best choice of surgical approach is
      discussed. METHODS: The authors describe a series of 25 patients who underwent
      surgical treatment for tumours situated in the lateral ventricles of the dominant
      hemisphere. They discuss the most influential factors in the choice of surgical
      approach, which must allow maximum exposure of the lesion and vascular feeding
      branches without damaging highly functional areas (motor, visual and language
      areas). In particular, they report their experience using a low transtemporal
      route, between the middle and inferior gyri, for removing tumours localized in
      the temporal horn and/or trigone which made it possible to keep postoperative
      visual and phasic deficits to a minimum. RESULTS: In 5 patients the approach was
      transfrontal, in 10 temporal, in 6 superior parieto-occipital and in 4
      transcallosal. Three patients died. Only 5 patients presented permanent deficits
      (anomia, apraxia and visual fields alterations). CONCLUSIONS: The size, site,
      hemisphere and vascularization of intraventricular tumours influence the choice
      of surgical approach. The basal transtemporal approach is particularly indicated
      to remove tumours of the temporal horn and trigone and it seems to reduce the
      risk of speech disturbances and alterations of posture.

PMID- 12232551
TI  - Osteochondroma of the spine: an enigmatic tumor of the spinal cord. A series of
      10 cases.
AB  - BACKGROUND: The aim of this study was to evaluate clinical, radiological and
      pathological features of vertebral osteochondromas with compressive myelopathy
      and to review the relevant English literature. Osteochondro-mas are common benign
      bony lesions of long bones but involvement of spine by solitary osteochondroma
      and its presentation as compressive myelopathy is rare. Most of the literature is
      in the form of case reports. METHODS: During a period of 20 years (1980-1999), 10
      cases of osteochondromas of the spine were encountered. Clinical, radiological
      and pathological features were reviewed. RESULTS: The age ranged from 13 to 45
      years (mean 25.3 years) and all except 1 were males. In 8 cases the pathology
      involved the cervical spine and in two cases dorsal spine was involved. All
      patients presented with progressive motor sensory deficit of 6 months to 30 years
      duration (mean 3.9 years). Decompressive laminectomy was carried out in all the
      patients. Fortunately, gradual and complete recovery was observed in all of them.
      CONCLUSIONS: Osteochondromas of the spine are not as rare as reported in the
      literature. In a young patient of compressive myelopathy this possibility should
      be considered. Magnetic resonance imaging, computed tomography and CT myelogram
      are useful in evaluating the size and extent of the lesion for subsequent
      surgical planning.

PMID- 12232552
TI  - Vertebral arterio-venous fistula presenting with intracranial hemorrhage.
AB  - Vertebral arteriovenous fistulas are rare lesions consisting of an abnormal shunt
      between the extracranial vertebral artery and the neighboring veins. The authors
      present a case of post-surgical high-flow left vertebral arteriovenous fistula
      presenting with intracranial hemorrhage. The patient underwent endovascular
      balloon occlusion of the fistula: after endovascular treatment a reduction of the
      flow was evident but the patient presented neurological deterioration related the
      occurrence of intraventricular-subarachnoid hemorrhage. Intracranial hemorrhage
      is a potential manifestation of high-flow vertebral AVF and a possible
      complication of endovascular fistula balloon occlusion. Direct endovascular
      occlusion of the vertebral artery may be primarily considered in selected cases.

PMID- 12232553
TI  - Brain metastases from hepatocellular carcinoma. A case report.
AB  - Brain metastasis from hepatocarcinoma are a decidedly rare occurrence in
      countries where this pathology is most frequent. The authors describe a case of
      metastases from hepatocellular carcinoma in a patient suffering from post-HBV
      hepatic cirrhosis with hemorrhagic onset. The "stroke-like" presentation of the
      cerebral localization of the disease can be explained by both the important
      vascularization of the tumor and the frequent hemocoagulative alterations caused
      by the cirrhosis. The importance of diagnostic neuroradiology is briefly
      addressed, with reference to the fundamental role played by MRI. Surgery of these
      lesions does not present any particular technical problems as long as they are
      located in accessible areas and the patient's general and neurological conditions
      allow it. Postoperative radiotherapy seems to improve the quality and quantity of
      residual life, although the number of patients described in the literature is too
      small to draw any definite conclusion. Promising molecular biology studies are
      under way to evaluate the role of oncosuppresor gene expression in
      hepatocarcinogenesis and in the way the disease spreads.

PMID- 12232554
TI  - Endocrine disorder as the only sign of chronic "non-hypertensive" hydrocephalus.
AB  - Three cases of "non-hypertensive" chronic hydrocephalus, 2 of which associated
      with early puberty and 1 with primary amenorrhea, are reported. Hormonal
      secretion deficiencies were confirmed by laboratory investigations. Only 1 of the
      3 patients was surgically treated with a shunting device.

PMID- 12232555
TI  - Pontine hemorrhage after frontal craniotomy. Report of a case.
AB  - This report describes the complication of pontine hemorrhage in a patient who had
      undergone supratentorial craniotomy for treatment of a frontal intracerebral
      hematoma. A literature review revealed no previous cases of pontine hemorrhage in
      this clinical scenario. Abnormal findings on neurological examination in the
      early postoperative period should alert the physician to the possibility of this
      complication.

PMID- 12232556
TI  - Thoracic epidural hemangiopericytoma. Case report.
AB  - Hemangiopericytoma is an uncommon mesenchymal neoplasm that rarely affects the
      spinal canal. We report a case of thoracic epidural hemangiopericytoma in a 39
      year-old man with symptoms of spinal cord compression studied by myelo-computed
      tomography (CT) and magnetic resonance imaging (MRI). Total resection was
      followed by complete recovery. Postoperative radiotherapy was performed. The
      clinical, radiological, and histological findings of epidural spinal
      hemangiopericytoma are reviewed in the light of relevant literature

PMID- 12232557
TI  - Radicular compression by lumbar intraspinal epidural gas pseudocyst in
      association with lateral disc herniation. Role of the posterior longitudinal
      ligament.
AB  - Among unusual abnormalities of the lumbar spine reported since the introduction
      of Computed Tomography (CT), the presence of gas lucency in the spinal canal,
      known as vacuum phenomenon, is often demonstrated. On the contrary, epidural gas
      pseudocyst compressing a nerve root in patients with a lateral disc herniation
      has rarely been reported. We report a case of a 44-year-old man who experienced
      violent low back pain and monolateral sciatica, exacerbated by orthostatic
      position, one week before admission. A lumbosacral spine CT showed the presence
      of vacuum phenomenon associated with a degenerated disc material and a capsulated
      epidural gas collection with evidence of root compression. A microsurgical
      interlaminar approach was carried out and, before the posterior longitudinal
      ligament was entered, a spherical "bubble" compressing the nerve roots was
      observed. The capsulated pseudocyst was dissected out, peeled off and excised en
      bloc. A large part of the posterior longitudinal ligament and the lateral disc
      herniation were removed. Postoperatively the patient was completely free of
      symptoms. The mechanism of exacerbation of pain was probably due to the increased
      radicular compression in the upright posture and, besides the presence of a
      lateral disc herniation, could be related to a pneumatic squeezing of gas from
      the intervertebral space into the well capsulated sac by the solicitated L4-L5
      motion segment. Histological study of the wall of the pseudocyst showed the
      presence of fibrous tissue identical to the ligament. We conclude that, in case
      of a lumbar disc herniation, it is recommended to perform a complete
      microdiscectomy and an accurate removal of the involved portion of posterior
      longitudinal ligament in order to prevent pseudocystic formations.

PMID- 12232558
TI  - Ossification of the ligamentum flavum in a Caucasian. Case report.
AB  - There have been few reports of ossification of the yellow ligaments causing
      spinal cord compression in Caucasian population. This disease is described mainly
      in Japanese patients and is termed as "Japanese disease". We describe the case of
      a 58-year-old Caucasian male with progressive paraparesis. Radiographic features
      were suggestive of ossification of the yellow ligaments in the lower thoracic
      level causing spinal cord compression. Early decompressive laminectomy and
      removal of the ossified ligament resulted in a marked clinical improvement. The
      etiological hypothesis, epidemiological, histological, clinical and radiological
      features of this disease are reviewed.

PMID- 12232559
TI  - Extremely rare complications in cerebrospinal fluid shunt operations.
AB  - The cerebrospinal fluid shunt operation, from its first realization in 1908 by
      Kausch till our days, is still of a significant importance for the long-term
      treatment of the internal hydrocephalus. Well known are many complications
      connected with the use of the valve systems (malfunction, infectious,
      overdrainage, secondary craniosynostosis and etc.). For a period of 17 years
      (1984-2000) at the Clinic of Pediatric Neurosurgery, Department of Neurosurgery,
      Sofia Medical University, 414 cerebrospinal fluid shunt operations were performed
      on children. 216 were drained to the right atrium of the heart, 198 to the
      peritoneal cavity. They were followed up by catamnesis until the year 2001. The
      authors describe 2 extremely rare cases with post-shunt complication as a result
      of a malfunction of the valve system, owing to a migration of the distal
      catheter: 1) in the anus; 2) in the urethra. In the first case the distal
      catheter perforated the colon transversum and by the way of the intestines went
      out through the anus. In the second case the distal catheter protruded out of the
      body through the bladder and the urethra. Their clinical appearance, the
      diagnostic examinations and the operative treatment are shown.

PMID- 12232560
TI  - Atrial fibrillation following investigation of rhythm management: AFFIRM trial
      outcomes. What might be their implications for arrhythmia control?

PMID- 12232561
TI  - Plasma levels of brain natriuretic peptide: a potential marker for HIV-related
      cardiomyopathy.
AB  - One of the most common and life-threatening cardiovascular complications of HIV
      infection is severe global left ventricular dysfunction due to primary heart
      muscle disease. At present, there is no single, cost-effective and reliable
      method of identifying the highly prevalent HIV-related cardiac dysfunction.
      Nonetheless, growing evidence supports the hypothesis that brain natriuretic
      peptide measurement has the potential to detect patients who develop HIV-related
      cardiomyopathy. If true, this hypothesis would have important clinical and public
      health implications.

PMID- 12232562
TI  - HR (Venoruton1000, Paroven, 0-[beta-hydroxyethyl]-rutosides) vs. Daflon 500 in
      chronic venous disease and microangiopathy: an independent prospective,
      controlled, randomized trial.
AB  - OBJECTIVES: The aim of this study was to demonstrate whether and how HR
      (Venoruton(1000), Paroven, 0-[beta-hydroxyethyl]-rutosides) and Daflon (diosmin,
      500 mg) were comparatively effective in improving the microcirculation in venous
      hypertension and microangiopathy. METHODS: A group of 90 patients with severe
      venous hypertension due to chronic venous insufficiency, ankle swelling, and
      lipodermatosclerosis were included. After informed consent, patients were
      randomized into a Venoruton and a Daflon (DF) group: patients in the Venoruton
      group received oral HR (2 g/day for 8 weeks); those in the Daflon group received
      three 500-mg tablets daily every 8 hours. The two groups were comparable for age
      and sex distribution. The mean age was 41 years (SD +/- 11) in the Venoruton
      group (46 patients) and 41.3 (SD +/- 12) in the DF group (44 patients). RESULTS:
      There were no differences in microcirculatory parameters between the Venoruton
      and DF treatment groups at inclusion. There was no significant change between
      inclusion and measurements at 8 weeks in the DF group. In comparison, a
      significant decrease (P < .05) in RF (resting skin flux) and RAS (rate of ankle
      swelling) was observed in the Venoruton group (P < .001). The decrease in
      capillary filtration was associated with improvement in signs and symptoms
      (measured by an analogue scale line) (P < .05). Symptomatic improvement was
      clinically and statistically significant and important only in the Venoruton
      group. No side effects and no drop-outs were observed. CONCLUSION: Venous
      microangiopathy was improved by the treatment with Venoruton. The comparison with
      Daflon indicates that HR is comparatively more effective both on microcirculatory
      parameters and on signs and symptoms.

PMID- 12232564
TI  - Comparison of verapamil and ibutilide for the suppression of immediate
      recurrences of atrial fibrillation after transthoracic cardioversion.
AB  - BACKGROUND: Verapamil and ibutilide blunt the atrial fibrillation-induced
      shortening of atrial refractoriness that may predispose to an immediate
      recurrence of atrial fibrillation after cardioversion. This study compared the
      efficacy of verapamil and ibutilide in preventing an immediate recurrence of
      atrial fibrillation. METHODS AND RESULTS: Transthoracic cardioversion was
      performed in 223 patients with atrial fibrillation. Atrial fibrillation recurred
      within 10 minutes after cardioversion on two occasions in 21 patients (9.4%).
      Twenty of these patients were randomly assigned to receive an infusion of either
      0.15 mg/kg of verapamil at a rate of 2 mg/min (11 patients), or 1 mg of ibutilide
      over 10 minutes (9 patients). Eight patients (73%) had another episode of
      immediate recurrence of atrial fibrillation after verapamil, compared to two
      patients (22%) after ibutilide (P<0.05). Including the results after crossover,
      immediate recurrence of atrial fibrillation occurred in 8 of 12 patients (67%)
      who received verapamil, compared to 3 of 16 patients (19%) who received ibutilide
      (P=0.02). Verapamil and/or ibutilide successfully prevented immediate recurrence
      of atrial fibrillation in 17 of 20 patients (85%). After 700 days of follow-up,
      there was no significant difference in the recurrence rate of atrial fibrillation
      between the patients in whom immediate recurrence of atrial fibrillation was
      prevented by verapamil and/or ibutilide and the patients who were successfully
      converted to sinus rhythm and did not have immediate recurrence of atrial
      fibrillation. CONCLUSIONS: Ibutilide is more effective than verapamil in
      preventing immediate recurrence of atrial fibrillation. Suppression of immediate
      recurrence of atrial fibrillation by ibutilide and/or verapamil may allow for
      long-term maintenance of sinus rhythm postcardioversion as often as in patients
      who do not experience immediate recurrence of atrial fibrillation.

PMID- 12232563
TI  - Oxidized low-density lipoprotein receptor LOX-1 and apoptosis in human
      atherosclerotic lesions.
AB  - BACKGROUND: Lectin-like oxidized LDL receptor-1 (LOX-1), a novel receptor for
      oxidized low-density lipoprotein, mediates oxidized low-density lipoprotein
      induced apoptosis of endothelial cells, monocyte adhesion to endothelium, and
      phagocytosis of aged cells. The present study examined the role of LOX-1 and
      apoptosis in human atherosclerotic lesions. METHODS AND RESULTS: Grafted vein (n
      = 8), human carotid artery endarterectomy (n = 11), and normal human internal
      mammary artery (n = 8) specimens were used to study the expression of LOX-1 and
      apoptosis. LOX-1 expression was determined by reverse transcriptase-polymerase
      chain reaction, Western analysis, and immunostaining. Presence of apoptosis was
      determined by fluorescent in situ nick end-labeling staining and by the presence
      of poly (ADP-ribose) polymerase protein (an apoptotic marker). Expression of LOX
      1 was significantly increased in atherosclerotic grafted vein and carotid artery
      specimens compared with that in normal arteries. LOX-1 was expressed in
      endothelial cells, macrophages, and smooth muscle cells. LOX-1 was extensively
      expressed in the new blood vessels in the core of advanced atherosclerotic
      lesions. Double immunostaining showed LOX-1 expression to be colocalized with
      apoptotic cells. Fluorescent in situ nick end-labeling staining showed that the
      apoptotic cells were present mostly in the rupture-prone regions of the
      atherosclerotic plaque. CONCLUSION: These observations indicate that LOX-1 is
      extensively expressed in the proliferated intima of grafted veins and in advanced
      atherosclerotic carotid arteries. Further, LOX-1 is colocalized with apoptotic
      cells. These observations may relate to the phenomenon of plaque rupture, and
      provide targets for developing new therapies.

PMID- 12232565
TI  - Cariporide for pharmacologic defibrillation after prolonged cardiac arrest.
AB  - BACKGROUND: We hypothesized that cariporide, a sodium-hydrogen exchange
      inhibitor, would be as cardioprotective during the global myocardial ischemia of
      prolonged cardiac arrest as it is in settings of coronary occlusion. METHODS AND
      RESULTS: Fifteen Sprague-Dawley rats were randomized to receive bolus injections
      of cariporide or placebo in a dose of 3 mgxkg(-1) into the right atrium either 5
      minutes before, or at 8 minutes after, onset of ventricular fibrillation.
      Ventricular fibrillation was electrically induced and untreated for 8 minutes.
      Precordial compression, together with mechanical ventilation, was then started
      and continued for an interval of 8 minutes prior to attempted resuscitation. All
      but one placebo-treated animal were successfully resuscitated. Spontaneous
      defibrillation with restoration of circulation was observed in both cariporide
      pretreatment and post-treatment groups but in none of the placebo-treated
      animals. Postresuscitation cardiac index, end-tidal CO(2), mean aortic pressure,
      left ventricular systolic pressure, left ventricular end-diastolic pressure, and
      left ventricular contractile and lusitropic functions (dP/dt(40), and -dP/dt)
      were significantly less impaired after cariporide, especially in the pretreated
      group, compared to electrically defibrillated controls. Postresuscitation
      ventricular premature beats were significantly reduced after cariporide. The
      duration of post-resuscitation survival was significantly increased in animals
      pretreated with cariporide. CONCLUSIONS: Cariporide, when administered prior to
      and during cardiac arrest, improved both the success of resuscitation and
      postresuscitation myocardial function.

PMID- 12232566
TI  - Contrast ultrasound targeted drug and gene delivery: an update on a new
      therapeutic modality.
AB  - The effective delivery of intravascular drugs and genes to regions of pathology
      is dependent on a number of factors that are often difficult to control. Foremost
      is the site-specific delivery of the payload to the region of pathology and the
      subsequent transport of the payload across the endothelial barrier. Ultrasound
      contrast agent microbubbles, which are typically used for image enhancement, are
      capable of amplifying both the targeting and transport of drugs and genes to
      tissue. Microbubble targeting can be achieved by the intrinsic binding properties
      of the microbubble shells or through the attachment of site-specific ligands.
      Once microbubbles have been targeted to the region of interest, microvessel walls
      can be permeabilized by destroying the microbubbles with low-frequency, high
      power ultrasound. A second level of targeting specificity can be achieved by
      carefully controlling the ultrasound field and limiting microbubble destruction
      to the region of interest. When microbubbles are destroyed, drugs or genes that
      are housed within them or bound to their shells can be released to the blood
      stream and then delivered to tissue by convective forces through the
      permeabilized microvessels. An alternative strategy is to increase payload volume
      by coinjecting drug- or gene-bearing vehicles, such as liposomes, with the
      microbubbles. In this manifestation, microbubbles are used for creating sites of
      microvessel permeabilization that facilitate drug or gene vehicle transport.
      Recent work in the emerging field of contrast ultrasound-based therapeutics, with
      particular emphasis on the delivery of drugs and genes to tissue through
      microvascular networks is reviewed.

PMID- 12232567
TI  - Nesiritide: a new drug for the treatment of decompensated heart failure.
AB  - Nesiritide, a recombinant human B-type natriuretic peptide, is the first in a new
      drug class for the treatment of decompensated heart failure. The drug binds to
      receptors in the vasculature, kidney, adrenal gland, and brain, and overcomes
      resistance to endogenous BNP present in patients with CHF. Nesiritide
      administration leads to a rapid and balanced vasodilatory effect, which results
      in a significant decrease in right and left ventricular filling pressures and
      systemic vascular resistance and at the same time in an increase in stroke volume
      and cardiac output without a change in heart rate. These early hemodynamic
      changes result in a rapid improvement in symptoms of heart failure. In addition,
      nesiritide lowers aldosterone, catecholamines, and endothelin-1 levels and its
      effect on the kidney leads to an increased natriuresis and diuresis without
      effect on serum potassium or renal function. Prior to its approval for clinical
      use, nesiritide was studied in 10 different clinical trials involving 941
      patients with moderate and severe CHF, including elderly patients, patients with
      both systolic and diastolic dysfunction, and patients with arrhythmias, renal
      insufficiency, and acute ischemic syndrome. In comparative studies with available
      vasoactive therapies frequently used for treatment of patients with decompensated
      heart failure, nesiritide was proven comparable in efficacy to inotropic drugs
      such as dobutamine, but superior in safety. In a recent study, nesiritide was
      found to be more effective and better tolerated than the vasodilator,
      nitroglycerin. The most common side effects expected with the use of nesiritide
      are headaches and decrease in blood pressure. At the recommended dose of
      nesiritide, headache was reported during the first 24 hours of treatment in 8% of
      patients and symptomatic hypotension in 4% of patients, compared to 20% and 5% in
      nitroglycerin-treated patients.

PMID- 12232569
TI  - Mountains on the moon: the role of imagination and style in science.

PMID- 12232568
TI  - Cocaine-induced channelopathies: emerging evidence on the multiple mechanisms of
      sudden death.
AB  - Sudden death due to cocaine in the absence of myocardial infarction has been
      attributed to the precipitation of life-threatening arrhythmias not unlike that
      due to antiarrhythmic drugs. Cocaine is a slow on-off sodium blocker and a fast
      on-off potassium blocker. Effects on repolarization are biphasic: At low
      concentrations, cocaine delays ventricular recovery, whereas at higher levels,
      cocaine hastens it. Two distinct clinical profiles emerge from case reports of
      electrocardiographically documented life-threatening arrhythmias attributed to
      cocaine. The first is monomorphic slow ventricular tachycardia or idioventricular
      rhythm that occurs in overdose situations and appears to reflect excessive sodium
      channel block; it may respond to sodium bicarbonate. The second is torsade de
      pointes that occurs in recreational users who have underlying risks for this
      tachycardia (such as fully or partially expressed congenital long QT syndrome)
      and reflects potassium channel blockade. These clinical observations can be
      explained by recent findings regarding the electrophysiologic effects of cocaine.
      Other patterns of severe arrhythmias due to cocaine may yet emerge.

PMID- 12232570
TI  - Adenomatous polyposis coli (APC) protein expression in primary and metastatic
      serous ovarian carcinoma.
AB  - The aim of this study was to investigate protein expression of adenomatous
      polyposis coli (APC) in primary and metastatic serous ovarian carcinoma. The
      expression of beta-catenin and E-cadherin was additionally analyzed. One hundred
      and thirteen primary (n = 56) and metastatic (n = 57) lesions were
      immunohistochemically stained for APC, E-cadherin, and beta-catenin. Staining
      extent was scored. Possible differences in immunoreactivity in primary and
      metastatic sites and the association between the proteins analyzed were evaluated
      statistically. Cytoplasmic immunoreactivity for APC was found in 67/113 (59%)
      tumors, most often in the majority (> 50%) of cells. E-cadherin was detected in
      102/113 (90%) carcinomas, while beta-catenin was expressed in 109/113 (97%)
      specimens. Nuclear expression of beta-catenin was seen in 3/113 (3%) specimens,
      all negative for APC. APC and beta-catenin were often coexpressed, but this
      finding failed to reach statistical significance (p = 0.11). A significant
      association was seen between E-cadherin and beta-catenin expression (p = 0.001).
      APC expression was comparable in primary and metastatic tumors (p > 0.05). In
      conclusion, APC expression is absent in a considerable number of both primary and
      metastatic ovarian carcinomas, but this finding is only rarely coupled to nuclear
      accumulation of beta-catenin. These findings support the role for beta-catenin
      signaling via the Wingless/Wnt pathway in ovarian carcinoma. The mechanism behind
      the down-regulated expression of APC in serous ovarian carcinoma and its
      significance has yet to be elucidated.

PMID- 12232571
TI  - Thymidine phosphorylase expression in gallbladder adenocarcinomas.
AB  - The expression of thymidine phosphorylase (TP), a potent chemotactic factor for
      endothelial cells, was studied in 60 adenocarcinomas of the gallbladder, by use
      of immunohistochemical techniques. Results on patterns of TP expression were
      correlated with angiogenesis (anti-CD31), histopathological variables, and
      patient survival. TP was frequently expressed in tumor cells, stromal cells,
      tumor-associated macrophages, and lymphocytes of gallbladder adenocarcinomas. The
      expression was mixed nuclear/cytoplasmic. However, only nuclear TP (TPnuc)
      expression by tumor cells was correlated with increased angiogenic activity. High
      angiogenesis, assessed as microvessel density (MVD), was the most significant
      prognostic factor. The subgroup of patients with TPnuc and medium/high MVD had
      the worst prognosis as evaluated by the survival curves. Furthermore, CD31+
      lymphocytes, frequently seen in carcinomas with high-fibroblastic TP reactivity,
      were connected with an improved survival. It is concluded that angiogenesis, as
      verified by multivariate analysis, is the most important prognostic factor in
      gallbladder carcinomas. In these tumors, high histologic grade and low CD31+
      lymphocytic infiltration are also independent predictors of poor prognosis. TP is
      associated with an aggressive phenotype apparently because of its anglogenic
      activity. Therapeutic strategies targeting TP may be of value in patients
      overexpressing this enzyme.

PMID- 12232572
TI  - Calcifying fibrous 'pseudotumor': clinicopathologic study of 15 cases and
      analysis of its relationship to inflammatory myofibroblastic tumor.
AB  - Calcifying fibrous pseudotumor (CFP) has been postulated to be a "late" stage of
      inflammatory myofibroblastic tumor (IMT). We analyzed 15 cases (8 females and 7
      males; aged 1 to 65 years). The anatomic distribution was wide, including 3 cases
      each in neck, mesentery/omentum, and GI tract and 2 cases each in mediastinum and
      paratesticular sites. Follow-up information was available in 10 patients (range 4
      to 228 months). Local recurrence occurred in 3 patients and was repeated in 2.
      Tumor size ranged from 0.6 to 25 cm. Lesions were well-circumscribed hypocellular
      spindle cell proliferations with dense stromal collagen, a lymphoplasmacytic
      infiltrate, and stromal calcifications. Features of conventional IMT were not
      seen. Immunostaining showed CD34 positivity in most cases as well as rare cells
      positive for smooth muscle actin and desmin, and consistent negativity for ALK-1
      and S-100 protein. These findings suggest that CFP is a distinctive benign
      mesenchymal neoplasm with a low risk for recurrence and, therefore, best labelled
      as "calcifying fibrous tumor." There is no convincing evidence to support an
      association between CFP and IMT.

PMID- 12232573
TI  - Lymph node lesion in adult-onset Still's disease resembling peripheral T-cell
      lymphoma: a report of three cases.
AB  - Adult-onset Still's disease (AOSD) is known to be a cause of fever of unknown
      origin. We describe the clinicopathologic, immunohistologic, and genotypic
      features of 3 patients with lymph node lesions from AOSD, which posed a serious
      diagnostic difficulty from peripheral T-cell lymphomas. The patients were 22-, 26
      , and 63-year-old Japanese women. At the onset of disease, all patients had
      multicentric lymphadenopathy in association with clinical and laboratory findings
      suggestive of a malignant lymphoma. None of the patients developed malignant
      lymphomas during the follow-up period. Histologically, the lesions were
      characterized by paracortical hyperplasia with prominent vascular proliferation.
      In the paracortical area, there was a mixed infiltrate including small-to-medium
      sized lymphocytes, variable numbers of eosinophils, plasma cells, and B
      immunoblasts. Polymerase chain reaction analysis demonstrated that neither clonal
      rearrangement of the T-cell receptor gamma-chain gene nor immunoglobulin heavy
      chain rearrangement was detected in any patient. Although AOSD appears to be a
      rare systemic inflammatory disorder, the lymph node lesion should be added to the
      differential consideration of benign lymph node lesions simulating node-based
      peripheral T-cell lymphoma.

PMID- 12232577
TI  - Images in pathology: intraoperative cytology of hydatid cyst.

PMID- 12232576
TI  - Images in pathology: multiple cytoplasmic vacuoles in a spindle cell liposarcoma.

PMID- 12232578
TI  - Low-grade fibrosarcoma (hyalinizing spindle cell tumor with giant rosettes) with
      pulmonary metastases at presentation: case report and review of the literature.
AB  - Hyalinizing spindle cell tumor with giant rosettes (HSCT) is presently considered
      a low-grade fibrosarcoma and is also considered a variant of low-grade
      fibromyxoid sarcoma by some. None of the HSCTs in the original series had
      manifested malignant behavior in the form of metastasis, but since that initial
      report, 2 patients have been reported with pulmonary metastases and another
      patient with multiple pulmonary nodules in the absence of an identifiable primary
      tumor. Our patient is the second recorded case of HSCT with pulmonary metastases
      at the time of diagnosis. A needle biopsy of the axillary mass in the present
      case consisted mainly of densely hyalinized collagen, whereas the lung nodules
      had the characteristic giant collagen rosettes surrounded by a bland spindle cell
      stroma. This case, in addition to at least 2 others in the literature, has
      demonstrated that the HSCT is a malignant neoplasm with the capacity to
      metastasize; however, the presence and even persistence of metastatic lesions in
      the lung has not altered to date an otherwise indolent clinical course. The fact
      should not be overlooked that the HSCT is a recently reported entity whose
      natural history and nosology are subjects of continuing observation, study, and
      discussion.

PMID- 12232579
TI  - Brain-invasive solitary fibrous tumor of the meninges: report of a case.
AB  - Solitary fibrous tumor is a mesenchymal neoplasm that most commonly arises in the
      pleura, but also in multiple extrapleural sites including, rarely, the meninges.
      Immunohistochemical findings facilitate its differentiation from other spindle
      cell lesions such as fibrous meningioma. Although the great majority of
      extrapleural solitary fibrous tumors behave in a benign fashion, only rare
      examples of brain-invasive tumors have been documented. We present a case of a
      brain-invasive solitary fibrous tumor arising in the meninges of a 40-year-old
      woman. The tumor was marked by focally prominent hypercellularity, moderate
      nuclear pleomorphism, and increased mitotic activity. Focal infiltration into the
      underlying brain parenchyma was observed. The tumor was CD34 positive and EMA
      negative.

PMID- 12232580
TI  - Lymph node infarction associated with infectious mononucleosis: report of a case
      resembling lymph node infarction associated with malignant lymphoma.
AB  - A completely infarcted lymph node should alert the pathologist to the high
      possibility of malignant lymphoma. The lymph node lesion of infectious
      mononucleosis (IM) shows marked histologic diversity and occasionally may be
      confused with malignant lymphoma. We report a rare case of IM showing extensive
      lymph node infarction whose lymph node lesion was similar to lymph node
      infarction associated with malignant lymphoma. This case describes a 32-year-old
      Japanese man who had signs and symptoms consistent with IM, which he was later
      proven serologically to have, but whose cervical lymph node showed extensive
      lymph node infarction with a thin area of granulation tissue beneath the capsule.
      The infarcted tissue contained numerous eosinophilic ghosts of large lymphoid
      cells. The thin granulation tissue was composed of numerous small lymphocytes,
      plasma cells, and histiocytes, in addition to large lymphoid cells including
      immunoblasts and granulocytes. CD20, CD3, and CD45RO immunostains revealed the
      mixed B- and T-cell nature of the ghosts of large lymphoid cells in the infarcted
      tissue as well as viable large cells in the granulation tissue. The patient was
      free from disease after 50 months' follow-up.

PMID- 12232581
TI  - Sclerosing epithelioid fibrosarcoma primary of the bone.
AB  - Sclerosing epithelioid fibrosarcoma (SEF) is an uncommon tumor originally
      described in soft tissues. We report a case of SEF primary of the left iliac bone
      in a 42-year-old woman. The tumor was grossly well circumscribed. The histologic
      examination disclosed a hypocellular neoplasm with densely hyalinized stroma. It
      was composed predominantly of small-to-moderate-sized round-to-ovoid cells,
      relatively uniform, often with clear cytoplasm, and arranged in nest, cord, and
      strand patterns. Because the distinctive morphologic patterns and the
      immunohistochemical profile of this entity may be mistaken for many different
      tumors, we here emphasize the differential diagnostic problems of this variant of
      fibrosarcoma. To our knowledge, this is the first tumor of this kind described in
      the bone.

PMID- 12232582
TI  - Rhabdoid epithelioid leiomyosarcoma of the uterine corpus: a case report and
      literature review.
AB  - A case of epithelioid leiomyosarcoma of the uterus with rhabdoid phenotype and
      early rhabdomyoblastic differentiation is described. A 72-year-old woman with a 5
      week history of increased abdominal girth was found to have a large pelvic mass.
      The uterus revealed a large intramyometrial and left adnexal necrotic tumor that
      had spread to the small bowel mesentery and to the anterior abdominal peritoneum.
      The tumor was an epithelioid leiomyosarcoma with rhabdoid phenotype and focal
      early rhabdomyoblastic differentiation, as confirmed by immunohistochemical and
      ultrastructural techniques. Also called composite extrarenal rhabdoid tumor
      (CERT), this lesion should be differentiated from malignant mixed mullerian
      tumor, rhabdomyosarcoma, endometrial stromal sarcoma, and pure rhabdoid tumors of
      the uterus. The recognition of a rhabdoid phenotype is of clinical importance
      since these tumors are prone to be aggressive.

PMID- 12232583
TI  - Cloning of the BPLA(2) Gene from Agkistrodon halys Pallas.
AB  - First strand cDNA synthesis was primed with synthetic oligonucleotide from total
      RNA extracted from the gland of the snake Agkistrodon halys Pallas. The pro
      BPLA(2) gene was then amplified by PCR and cloned into the pBS-ks vector. Its
      nucleotide sequence has been determined by analyzing the DNA sequence of three
      colonies containing the pro-BPLA(2) gene. The deduced amino acid sequence
      consists of 138 amino acids and agrees with the partly known amino acid sequence
      except for seven amino acid residues. The successful cloning of the BPLA(2) gene
      not only has made the determination of its total amino acid sequence possible,
      but also provided a good basis for further research work in the protein
      engineering of functional peptides from snakes.

PMID- 12232584
TI  - Expression of the Variable Region Genes of the Monoclonal Antibodies Against
      Metal-bound Tetrapeptide in E. coli.
AB  - The variable region genes of the light and heavy chains obtained from three stems
      of McAb against metal-bound tetrapeptide were joined into a single chain by a
      linker. A 39 bp fragment of the N-terminal of CGRP was joined to the C-terminal
      of the heavy chain to constitute the Lv-linker-Hv-CGRP single chain gene which
      was cloned into the vector pTC01 and expressed in E. coli 71/18. The molecular
      weight of the expressed product was approximately 26 kD as shown by SDS-PAGE. Its
      expression level was about 20%-30% to he total cellular proteins. The product was
      a soluble protein and showed binding activity with its hapten by indirect ELISA
      assay.

PMID- 12232585
TI  - Regulation of Hepatitis B Virus Gene Expression by Its Two Enhancers.
AB  - A linearized genome containing the entire HBV 3.5 kb mRNA transcriptional units
      was constructed. Based on it, a series of mutants with enhancer deletions or
      point mutations were generated. This system has served as a good model to study
      the regulation of hepatitis B virus gene expression by its two enhancers (ENI and
      ENII). The results showed that both ENI and ENII could increase the expression of
      HBsAg, and the two enhancers worked synergistically. They also could increase the
      expression of HBeAg, but the deletion of 2C and Ep of ENI had no effect on the
      expression of Hbe/cAg in the cytoplasm. The expression of C gene might be
      regulated mainly by ENII, but ENI could cooperate with the action of ENII. The
      data indicated that ENI and ENII might function differentially but cooperatively
      in regulation the transcription of the two 3.5 kb mRNAs which functioned
      distinctively.

PMID- 12232586
TI  - The Isolation and Structure Characterization of the Active Oligosaccharide DP-6
      from Cultured Panax ginseng Cells.
AB  - The oligosaccharins isolated from acid-hydrolyzed cultured cells of Panax ginseng
      are a mixture of DP-3 to 12. The samples were passed through an active carbon
      column, a Dowex (H(+)) column, and a Bio-Gel P-2 column to obtain
      oligosaccharides DP-6, 7 and 8. They were finally separated by HPLC and the DP-6
      oligosaccharide was obtained. Experiments showed that it could increase the
      growth rate of many cultured plant cells. Its structure was characterized by GC,
      GC-MS, FAB(-)-MS and (13)C-NMR measurements.

PMID- 12232587
TI  - Cloning and Expression of the cDNA Coding for Rat Peptidylglycine alpha-Amidating
      Monooxygenase.
AB  - The dDNA of genes encoding rat peptidylglycine alpha-aminating
      monooxygenase(rPAM) were cloned and their expression in E. coli studied. Three
      DNA fragments were isolated from the rat brain cDNA library using the methods of
      plaque hybridization and PCR. DNA sequencing showed that they contained the total
      coding sequence for rPAM-2. By using the sited-directed mutation and PCR
      recombination methods, we obtained intact genes coding for the rPHM domain, the
      rPAL domain and rPAM, respectively. Different plasmids of these genes controlled
      under T(7) or P(L) promoter were constructed and transformed into E. coli. The
      high-level expression of rPAM-N260 in E. coli was first observed and its
      antiserum was prepared for the immunoassay of natural or recombinant PAMs. By the
      analysis with SDS-PAGE and Western blot, the products of rPHM and rPAM in E. coli
      were detected, and the amount of rPHM reached over 10% of the total bacterial
      proteins. It was found that low temperature and copper ion obviously increased
      the stability and solubility of the rPHM expressed in E. coli.

PMID- 12232588
TI  - The DNA Sequence and Structural Characteristic of The 5'-Nontranscribed Spacer of
      Silkworm Attacus ricini rDNA.
AB  - We have found that the SacII-EcoRI fragment in the nontranscribed spacer (NTS) of
      silkworm Attacus ricini rDNA is a nuclear scaffold-associated region (SRA) and
      showed the function as the ARS element in yeast. This paper reports the sequence
      of this NTS region and the various characteristic potential functional motifs as
      analyzed by computer. It is 1 025 bp long and AT-Rich. With 9 bent DNA motifs, 10
      T-boxes, 5 A-boxes motifs, 13 topoisomerase II as well as 15 ARS consensus
      sequences. In addition, there are several dozens of inverted repeats and
      ATTA/TAAT, ATTTA/TAAAT, ATATTT/AAATAT motifs commonly believed to be the binding
      sites of many homeodomain proteins. These motifs, concentrated in the SAR region,
      may play very important role in the regulation of gene transcription and
      replication at the chromatin level.

PMID- 12232589
TI  - Influence of Lipid Composition on the Interaction of Apolipoprotein Model
      Peptides with Liposomes.
AB  - Two amphiphilic peptides, Ampl and Amp2, were synthesized according to the
      sequence of the lipid-binding domain in apoliporotein. Amp2 has a Val residue
      substituted for the Lys at the 4th position of Ampl. Interaction between Ampl /
      Amp2 and liposomes with different lipid compositions were compared by studying
      the blue shifts of the intrinsic fluorescence emission maxima, the peptide
      induced lipsome leakage and the quenching of tryptophan fluorescence by
      acrylamide. The influence of temperature on interactions was studied as well.
      Ampo1 interacted stronger with acidic lipids while Amp2 interacted stronger with
      zwitterionic lipids. The interaction was reinforced with the increasing extent of
      lipid unsaturation as well as with the increase of temperature. The lipid
      unsaturation had amore prominent effect.

PMID- 12232590
TI  - The Role of DNA Polymerase delta in HeLa Cell DNA Replication Studied by
      Antisense Technology.
AB  - We have investigated the biological role of DNA polymerase delta in HeLa cell DNA
      replication using antisense technology with the Lipofectin Delivery and the GPT
      selection method. Both of the oligonucleotides designed to inhibit the expression
      of DNA polymerase delta and alpha can specifically reduce the DNA replication
      level in HeLa cells. This is the first report directly proving that DNA
      polymerase delta plays an important role in mammalian cell DNA replication.

PMID- 12232591
TI  - Purification and Characterization of DNA Helicase BstH1 from Bacillus
      stearothermophilus.
AB  - We have partially purified a DNA helicase BstH1 from Bacillus stearothermophilus
      through Polymin P precipitation, ammonia sulfate precipitation and column
      chromatographic steps with Pheny1-Sepharose, DEAE-cellulose, phosphocellulose,
      FPLC Mono Q and Superose 12. Bsth1 possesses a DNA-Dependent ATPase activity in
      the presence of Mg(2+). The ATPase activity of BstH1 is differentially stimulated
      by the presence of different types of nucleic acids. BstH1 has an optimal ATPase
      activity at 55 degrees. The DNA helicase activity of BstH1 requires a 3'-terminal
      single-stranded DNA binding site to initiate the unwinding reaction in the 3'
      right curved arrow 5'direction. BstH1 can unwind blunt-ended duplex DNA in a
      concentration-dependent manner.

PMID- 12232592
TI  - Cloning of the LAC4 Promoter from K. lactis and Studies on the Function of its
      UASII.
AB  - The -661 - +21 bp region of the LAC4 gene form K. lactis CBS141 was obtained by
      PCR technique and fused with the lacZ gene from E. coli to construct and
      expression vector YFD 114. It was then transformed into K. lactis Y167. The
      function of the cloned LAC4 promoter was tested by induction with galactose,
      lactose, sorbitol or IPTG. The results revealed that galactose had higher
      inducing effect than lactose while sorbitol and IPTG had no inducing effect. The
      insertion of chemically synthesized LAC4 UASII at just the upstream of the cloned
      LAC4 promoter could increase its basic and induced expression level. The extents
      of increase were different with the orientation and the copy number of the
      inserted UASII.

PMID- 12232593
TI  - The Recombination and Expression of a Chimeric Antibody Light Chain Gene in Cells
      of Silkworm Bombyx mori.
AB  - A chimeric immunoglobulin light chain gene had been expressed in a baculovirus
      expression system, which was achieved by infecting the silkworm cells with the
      recombinant virus r-NPVL2 containing the cDNA of immunoglobulin against a small
      cell lung cancer. PCR analysis and Southern hybridization proved that the
      antibody light chain cDNA hand been integrated into the modified BmNPV genome.
      Expression products of human-mouse chimeric antibody light chain in the silkworm
      cells were detected by both Western blot and ELISA.

PMID- 12232594
TI  - Cooperation of HDL Receptor and Hepatic Lipase in the Selective Uptake of HDL(2)
      CE by Rat Hepatic Sinusoidal Cells.
AB  - The recombined (3)H-CE-HDL(2)(rHDL(2)) keeps the biological activities of the
      native HDL(2). After rat hepatic sinusoidal cells were incubated with rHDL(2) at
      37 degrees for 3 h (normal group), the cell-endocytic cpm was 995-/+147(mean-/+s,
      n=2). After the cells were further incubated for 2 h, the cell-release TCA
      precipitable cpm and the TCA-supernatant cpm were 78-/+32 and 12-/+9
      respectively. These values were 339-/+62, 19-/+11 and 9-/+5 respectively in the
      acetylimidazole-modified group, and 542-/+78, 34-/+14 and 9-/+8 respectively in
      the heparin-pretreated group. Our results suggested that: (1) Rat hepatic
      sinusoidal cells internalize HDL(2) and take up HDL(2)-CE by its HDL receptor,
      and HDL(3) was secreted out of the cells by retroendocytosis. (2) Hepatic lipase
      (HL) induces directly the selective uptake of HDL(2)-CE by the cells. (3) There
      is cooperation between the HDL receptor and HL in the selective uptake of HDL(2)
      CE by the cells.

PMID- 12232595
TI  - Interaction between the Anion Exchange Protein and the Glucose Transport Protein
      in Human Red Cell Membranes.
AB  - Cytochalasin B was used to inhibit the glucose transport through the glucose
      transport protein (GluT-1) in red cell membranes. It was observed that the anion
      transport was increased at the same time. The rate of anion transport was also
      increased when GluT-1 was bound with its substrate molecule-glucose. On the other
      hand, the experimental result on the relationship between glucose transport and
      Cl(-) concentration showed that K(m) was decreased and V(max) increased following
      the increase of Cl(-) concentration. There would be a bidirectional linkage
      between Band 3 (anion exchange protein) and GluT-1 in the intact red cell
      membranes. In other words, the conformation change of membrane protein could
      affect the function of other kinds of membrane proteins.

PMID- 12232596
TI  - Sequence Analysis of the Oligosaccharides from Scarlet Runner Bean Lectin.
AB  - Two oligosaccharide chains from scarlet runner bean (Phaseolus coccineus var.
      rubronanus) lectin (PCL) were obtained by hydrazinolysis, Bio-Gel P-2 column
      chromatography, NaBH(4) reduction and then separated on a Bio-Gel P-2 column. The
      oligosaccharides were methanolysed, acetylysed and then transformed into
      derivatives of trimethylsilane. Gas chromatographic studies of these two
      derivatives showed that their compositions were: Man(8)XylGlcNAc(2)
      (oligosaccharide I) and Man(6)XylGlcNAc(2)Fuc (oligosaccharide II). The size of
      these two oligosaccharides after digestion by alpha-mannosidase, beta-xylosidase
      and alpha-fucosidase separately, were determined on a standardized Bio-Gel P-4
      column. Thus the sequences of these two oligosaccharides were celucidated as:
      (Manalpha)(7)ManBetaXylBeta(GlcNAc)(2) and
      (Manalpha)(5)ManbetaXylbeta(GlcNAc)(2)Fucalpha.

PMID- 12232597
TI  - Effects of CF(0) Proton Flow on the Distribution of Light Energy Between PSI and
      PSII.
AB  - The Influence of energy transfer inhibitors of ATP synthase on the chlorophyll
      fluorescence quenching of thylakoids was studied by the saturation pulse method.
      Triphenyltin chloride (TPT) treatment could result in an increase of q(Q) and a
      decrease of q(E) of the thylakoids, but DCCD could not. This increase could be
      abolished when the deltapH across the thylakoid membrane was dissipated by
      uncouplers (1O mM NH(4)Cl plus 1&mgr;M nigericin) or in higher salt medium which
      could relieve localized protons on the thylakoid membrane. In the electron
      transport system of H(2)O right curved arrow PD(0X) or H(2)O right curved arrow
      PBQ coupled with PSII. The stimulatory effect of TPT on q(Q) also diminished. By
      the methods of modulated fluorescence and low temperature fluorescence
      measurement we observed that TPT markedly increased the imbalance of the
      distribution of light energy between PSI and PSII in favor of PSII. These results
      suggest that the CF(0) proton flow could influence the light energy distribution
      between the two photosystems. This might be materialized by the regulation of the
      membrane-localized protons on the photochemical efficiency of photosystem II.

PMID- 12232598
TI  - Large-scale Homologous Analysis of Genome Sequence.
AB  - We described a new method for the large-scale homologous analysis of genome
      sequences, which used hashing technique combined with sparse dynamic programming
      to get a sequence alignment. Three examples, the plant chloroplast genomes, the
      mammalian T-cell receptors C(alpha)/C(delta) gene loci and the mammalian gamma
      crystallin gene clusters were analysed. The results showed that the method was
      more rapid to obtain accurate enough data and might be useful in genome analysis.

PMID- 12232599
TI  - Identification of the Photoaffinity-labeled Abscisic Acid Binding Proteins from
      Maize Root Microsome.
AB  - ABA binding protein (ABA-BP) was solubilized with 0.2% (W/V) Triton X-100 from
      the microsomal membrane of maize root, with a specific binding activity of 0.56
      pmol ABA/g FW. When ABA was cross-linked to its binding sites by irradiating the
      microsomal proteins with light of 330 nm after incubation with low levels of H(3)
      (-/+)ABA, it was found that this kind of photoaffinity labeling was specific to
      ABA-BP. On PAGE and SDS-PAGE three major protein bands with molecular weights of
      72 kD, 47 kD and 37 kD were found with high radioactivity.

PMID- 12232600
TI  - The Effect of Tunicamycin on the Interaction of Fibronectin and HT1080 Cells.
AB  - We have found that the binding affinity of human plasma Fn to HT1O80 cell treated
      with TM was 2.61x1O(-8) M, the number of binding sites was 4.24x1O(4)/cell, while
      those of the control group was 2.50x1O(-8) M and 2.13x1O(5)/cell respectively.
      These results indicate that, the Fn binding sites on the cell surface decreased
      by 80% after TM treatment. The binding affinity of FnR in the TM-treated cell did
      not alter.

PMID- 12232601
TI  - Studies on the Function of Disulfide Bond Cys(112)-Cys(115) in Arrowhead
      Proteinase Inhibitors.
AB  - Two cysteine residues which compose the disulfide bond Cys(112)-Cys(115) in the
      arrowhead inhibitor were replaced by Ala and Ser respectively, using site
      directed mutagenesis. The mutant has similar inhibitory activities as that of the
      wild type. The result suggests that the disulfide bond of Cys(112)-Cys(115) in
      the arrowhead inhibitor is not indispensable to its inhibitory activity.

PMID- 12232602
TI  - Assignment of Proton Resonances and Conformational Characterization of
      Oligodeoxyribonucleic Acid d(CCGTACGG) in Solution.
AB  - Lycobetaine prepared from lycorine is a new anticancer agent. The experimental
      and quantum pharmacological studies revealed that lycobetaine can interact with
      DNA by intercalation, preferentially into GO base pairs. In order to provide
      detailed interaction model of lycobetaine-DNA, a self-complementary
      octanucleotide d(CCGTACGG) was designed and synthesized by using new HELP (high
      efficiency Liquid phase) According to its nature, the sample was prepared to the
      desired final concentration by adding salt and buffer solutions. Two-dimensional
      (1)H-(1)H COSY and NOESY spectra in 99.8% D(2)O and 95% H(2)O were recorded for
      the duplex, and the NMR techniques of presaturation and WATERGATE were applied to
      water suppression. Protons of every spin system were identified by their scalar
      couplings, then through their special couplings all protons in the molecule were
      assigned except the poorly resolved H5' and H5' ' resonances. The chemical shifts
      of exchangeable protons and NOE intensities of nonexchangeable protons indicate
      qualitatively that the d(CCGTACGG) helix is right-handed B-DNA in aqueous
      solution.

PMID- 12232603
TI  - Protein Engineering of Insulin: [B9Glu, B10Asp] Human Insulin.
AB  - B9Ser and B10His of the insulin B chain are substituted respectively by Glu and
      Asp using a gapped duplex DNA approach for site-directed mutagenesis. A mutant
      insulin-[B9Glu, B10Asp] human insulin was obtained. The receptor binding capacity
      of the mutant insulin is 34.4% as that of porcine insulin. However, the in vivo
      biological activity of [B9Glu, B10Asp] human insulin is almost as the same as
      that of porcine insulin.

PMID- 12232604
TI  - Cloning of a Tumor Antigen-related Gene in Small Cell Lung Carcinoma.
AB  - The Small Cell lung Carcinoma cell line NCI-H128 cDNA library constructed in
      Lambda gtll was screened by tumor associated antigen specific monoclonal antibody
      2F7. The No.4 positive clone was further investigated. The lysogen of the No.4
      clone could be induced at 42 degrees to produce 165 kD fusion protein by IPTG.
      This fusion protein can be detected by both the monoclonal antibody 2F7 and the
      anti-beta-galactosidase monoclonal antibody. Antigen Competitive Assay showed
      that the fusion protein purified by PAGE could compete with the natural tumor
      associated antigen on the membrane and combine with the monoclonal antibody 2F7.
      PCR reaction showed the inserted DNA fragment of No.4 Clone to be about 1.3 kb.
      The DNA inserted fragment was sub-cloned into the plasmid vector Bluescript-sk.
      Northern blot showed that it was specific for H128 cell line. These results
      showed that the gene of the tumor associated antigen which specifically reacted
      with the monoclonal antibody 2F7 was cloned.

PMID- 12232605
TI  - A Structure-function Analysis of the Human Ciliary Neurotrophic Factor.
AB  - The ciliary neurotrophic factor (CNTF) plays a very important role in the
      development and regeneration of the nervous system. In this study, the prediction
      of secondary structure and the hydrophobicity analysis of human CNTF were
      performed according to the amino acid sequence deduced from the nucleotide
      sequence of the cDNA. Based on the results of the prediction of structure, the
      human CNTF gene was modified by insertion and deletion mutagenesis. The various
      mutants were all highly expressed in E. coli. The recombinant proteins were
      purified from bacterial via DEAE A-50 and Sephacryl S-200 chromatography, and
      their survival-promoting activities were determined by using cultures of the
      dorsal root ganglion neurons of embryonic chick. The results showed that the
      alpha-helixes in CNTF were critical for the biological activity and the flexible
      C-terminus of human CNTF was not essential. Our data also indicated that the
      middle and the tail part of the D-helix might play crucial roles in the
      biological functions of CNTF.

PMID- 12232606
TI  - Construction and Expression of Mouse-human Chimeric Antibody SZ-51 Specific for
      Human Activated Platelets.
AB  - SZ-51, a murine monoclonal antibody (McAb) specific for alpha-granule membrane
      protein (GMP-140) on the surface of the activated human platelets, has shown
      promise for thrombus imaging and thrombolysis. In order to reduce the
      immunogenicity of the murine McAb SZ-51 in man and to obtain a high level of
      antibody production, we constructed two chimeras (alpha-Lys17-51BVK/Hu, alpha
      Lys30-51VH/Hu) by joining the variable regions gene of mouse antibody to the
      constant regions gene of human immunoglobulin (Ig)(gamma1,k). Both chimeric genes
      were cloned into two selectable expression vectors separately, which were co
      transfected into a non-Ig secreting murine myeloma cell line SP2/0 with the
      Lipofectin reagent. One transfectoma, which showed stable antigen (GMP-140)
      binding ability and a high level expression of 5 mg/L, was obtained.
      Immunoblotting analysis demonstrated that the chimeric antibody in the
      supernatant, like the native mouse SZ-51, had the characteristic of binding to
      GMP-140. In addition, the chimeric antibody can bind competitively to activated
      platelets with (125)I-labeled mouse SZ-51. Therefore, the SZ-51 chimeric antibody
      may be a potential agent for the diagnosis and therapy of thrombotic diseases in
      future.

PMID- 12232607
TI  - Cloning and Expression of the Cytochrome P-450nor2 cDNA from Cylindrocarpon
      tonkinense.
AB  - Cytochrome P-450nor is involved in the fungal denitrification and acts as a
      nitric oxide reductase. The cDNA library from Cylindrocarpon tonkinense was
      constructed with lambdagtll, and screened with antibodies. From the positive
      clones, the P-450nor2 cDNA fragments were recovered, and subcloned into the
      expression vector pYES2, then expressed in the yeast system. Western blot
      analysis showed that the expressed protein was hybridized with the antibody.
      Enzyme assay indicated that the expressed protein had the activities of P
      450nor2, which reduced NO to form N(2)O, employing NADH or NADPH as the sole
      electron donor.

PMID- 12232608
TI  - The Construction of GPRP-scu-PA(144-411) cDNA and the Study of Its Properties.
AB  - A synthetic nucleic acids fragment encoding the GPRP peptides was linked with the
      scu-PA (144-411) cDNA at its 5' end, and was subsequently inserted into the
      expression vector pKK233-2 and expressed in E. coli with a level of 5% of the
      total bacterial proteins. The expressed product of GPRP-scu-PA (144-411) cDNA was
      purified by affinity chromatography. Its < italic>K(m) was 40 &mgr;M, with the
      clotlysis rate 2-3 times of that of LUK, and the fibrin affinity 6 times higher
      than that of LUK. At the same time it had a low affinity for fibrinogen. These
      results showed that the GPRP peptide fragment was able to improve the fibrin
      specific affinity of urokinase.

PMID- 12232609
TI  - Changes of Myocardial Muscarinic Receptor during Septic Shock of the Rat.
AB  - The present study reports the structural and functional changes of myocardial
      muscarinic receptor during early and late septic shock, Septic shock was induced
      by caecum ligation and puncture (CLP). The results showed that the number of M
      receptor on sarcolemma (SL) increased and that on the light vesicle (LV)
      decreased during early septic shock. The (3)H-QNB binding of M receptor on SL
      increased by 33.37%. By contrast during late septic shock, the number of M
      receptor on LV increased and that on SL decreased. The (3)H-QNB binding of LV M
      receptor was increased by 29.26%. At the same time phosphorylation of the M
      receptor was decreased during early septic shock and increased during late septic
      shock. These results suggest that the changes of M receptors may be related to
      the myocardial dysfunction during septic shock.

PMID- 12232610
TI  - The Spectroscopic Study of E. coli Arginyl-tRNA Synthetase (ArgRS) and its
      Mutants.
AB  - The conformation of native enzyme ArgRS and its mutants ArgRS306KA, ArgRS306KR
      and ArgRS381KA was studied by absorbance spectrum, Difference spectrum with
      solvent perturbation, fluorescence spectrum and CD spectrum. The results showed
      that the chromophores of ArgRS306KR and ArgRS306KA had shifted to different micro
      environments in comparison to the native enzyme. Compared to the native enzyme,
      ArgRS306KA had and even bigger conformational change than ArgRS306KR, while the
      conformation difference between ArgRS381KA and ArgRS was not big enough to be
      perceivable in the spectrum. The analysis of CD spectrum showed the less the
      percentage of beta-turn in the ArgRS mutants, the lower the activity of the
      mutants. The conclusion can be drawn that the positive charge of Lys306 is very
      important to maintain the conformation of ArgRS, the change of conformation might
      be mainly responsible for the loss of enzyme of the mutants, while the
      substitution of Lys381 seems to cause no perceivable change of the enzyme
      conformation.

PMID- 12232611
TI  - Denaturation of Copper Zinc Superoxide Dismutase by Guaniding Hydrochloride.
AB  - The electron-transfer reaction between Fe(CN)(6)(4-) and copper zinc superoxide
      dismutase was used to detect the conformational changes of the active site of the
      enzyme. The analysis of the absorption, CD, ESR and fluorescence spectrum has
      provided the information of the conformational changes of the enzyme molecule at
      different sites. It was shown that inactivation occurred before the
      conformational change of the enzyme molecule. The results of kinetic analysis
      showed that conformational changes of the active site correlated closely with the
      changes of enzyme activity. Although being a relative stable metalloenzyme,
      copper zinc superoxide dismutase has a relative flexible active site.

PMID- 12232612
TI  - Functional Domains of the Regulatory Factor PHO81 of Saccharomyces cerevisiae.
AB  - It is found that minor changes around the basic motif (88-160) and the acidic
      motif (771-810) of the PHO81 protein can lead to the constitutive expression of
      the acid phosphatase gene (PHO5), and the two motifs work cooperatively. The
      PHO81 protein has six ankyrin repeats, which are the recognition sites of PHO81
      protein with the PHO80-PHO85 protein complex. It is found that the ankyrin
      repeats 1,2,4,5 and 6 are important for the PHO81 protein, but the deletion of
      Pro(509) and Leu(510) in ankyrin repeat 3 does not affect the PHO81 protein. We
      have found a candidate nucleoplasmin-like nuclear location sequence at 701-719 of
      the PHO81 protein and the deletion of the corresponding DNA fragment inactivates
      the PHO81 protein. However, when the conservative amino acids Arg701 and Lys702
      are constituted by Ser and Gln, or Lys717 replaced by Asn, or Arg719 is turned to
      Ser, the function PHO81 protein is not affected.

PMID- 12232613
TI  - The Effect of Yeast Transcriptional Factor PHO2 on the Gene Expression of PHO5,
      HIS4 and HO.
AB  - Yeast PHO2 protein plays a role in the expression of several different genes and
      acts as a multiple global activator. Here we report the comparison of the effect
      of PHO2 protein on the expression of PHO5, HIS4 and Ho genes. In the PHO2
      defective yeast strain, PHO5 gene could not be depressed in low Pi and the
      expression of the HIS4 and HO genes was decrease to 25% and 40% of the normal
      level respectively. When the PHO2 gene carried by low copy shuttle vector was
      transformed into this strain, the expression of the three genes could be
      restored. Previously the PHO2 gene was mutated on its conspicuous regions with
      site-directed mutagenesis, deletion and linker insertion. Here the effects of
      these mutations on these genes were compared.

PMID- 12232614
TI  - The Construction of T7 Promoter-based His(6)-tagging Vectors and the Single-step
      Purification of the Expression products.
AB  - T7 promoter-based fusion expression vectors have been constructed that directed
      the synthesis of heterologous proteins in E. coli as fusions with a stretch of
      six consecutive histidine residues His(6) at N Terminus. The vectors were also
      featured with strong T7 promoter, terminator, translational start, multiple
      cloning sites with seven unique restriction sites in all three reading frames and
      the f1 phage origin which allows the packaging of single-stranded plasmid,
      mutagenesis and DNA sequencing without subcloning steps. In most cases, expressed
      fusion proteins are soluble. The His(6) tag allows the fusion proteins purified
      in one step by immobilized metal (Ni(2+)) chelation affinity chromatography in
      the denatured or native state. As an example of the general utility of these
      expression vectors, the His(6)-fused catalytic subunits of mouse cAMP-dependent
      protein kinase were expressed with high activity by using these vectors and could
      be purified to homogeneity in one step.

PMID- 12232615
TI  - A T7 Promoter-based Versatile Expression Vector System.
AB  - A family of T7 promoter-based versatile expression plamides for E. coli Were
      constructed. These vectors were featured strong T7 promoter, translational start,
      stop elements, a multiple cloning site with eight unique restriction sites in all
      three reading frames and f1 phage origin which allows packaging of single
      stranded plasmid, mutagensis and gene sequencing without subcloning steps. With
      these vectors recombinant proteins can be expressed in mature or short fusion
      forms. Many heterolegous genes have been highly expressed using these vectors,
      most of them were expressed in soluble and active forms.

PMID- 12232616
TI  - The Construction and Application of the Multi-copy Integration Vector in K.
      lactis.
AB  - The vector pIRK was constructed by using a 2.2 kb EcoRI fragment of rDNA from
      Kluyveromyces lactis for targeted homologous recombination, with the URA3 gene
      from Saccharomyces cerevisiae acting as a selection marker. By the examination of
      the copy number, stability and chromosomal location of the vector in K. lactis
      transformants the results demonstrated that: (1) of the different transformants,
      the average copy number of the plasmid pIRK was 120 per cell; (2) after 50
      generations of growth in rich medium, the vector displayed high stability. (3)
      all integration events occurred in the chromosome IV where genomic rDNA located.
      Using this vector, the LAC4 gene cloned from K. fragilis was expressed. The yield
      of beta-galactosidase related directly to the vector's copy number. The highest
      activity of beta-galactosidase produced by transformants was 8.6 times higher
      than that produced by the wild type strain of K. fragilis under the same
      conditions.

PMID- 12232617
TI  - Studies on the Potential Phosphorylation Sites of the Yeast PHO2 Factor.
AB  - We report here that PHO2 protein is also phosphorylated by an unidentified
      protein kinase. A Ser-230 to Ala mutation in the consensus sequence (SPIK)
      recognized by cc2/CDC28-related kinase in the PHO2 protein led to the complete
      loss of its ability to activate the transcription of PHO5 gene. Further work
      showed that Pro-231 to Ser mutation inactivated PHO2 protein as well, while Ser
      230 to Asp mutation did not affect PHO2 activity. Since PHO2 Asp-230 mutant
      mimics Ser-230 phosphorylated PHO2, we postulate that only phosphorylated PHO2
      protein could activate the transcription of the PHO5 gene. The results of in
      vitro phospho-labelling experiments showed that the whole cell extract of the
      YPH499 strain grown under low phosphate conditions phosphorylated GST
      (glutathione S-transferase)- PHO2 (wild type) fusion protein, but not the GST
      PHO2 mutant (Pro-231 to Ser) protein in which the putative phosphorylation
      sequence was destroyed. We therefore propose that the PHO2 protein may also be
      phosphorylated in vitro at Ser-230, and the phosphorylation of this site may be
      necessary for its function in controlling PHO5 gene expression.

PMID- 12232618
TI  - Two Chain "Insulin/Insulin-like Growth Factor-I" Hybrids.
AB  - The two chain "Insulin/Insulin-like Growth Factor-I" hybrids, Ins/IGF-I(8) and
      Ins/IGF-I(11), were obtained by means of enzymatic semisynthesis, using
      desoctapeptide insulin (DOI) and the octapeptide and undecapeptide chemically
      synthesized according to the sequence 22-29 and 22-32 of IGF-I respectively as
      the starting materials. Comparative studies of the molecules with insulin
      indicate that the hybrid molecules retain in vivo the full activity of insulin.
      So the replacement of B27Thr by Asn and B30Ala by Thr, and the exchange of the
      sequence orders of B25 and B26, B28 and B29, as well as the extension of
      tripeptide (Gly-Tyr-Gly) at the B30 do not affect insulin activity.

PMID- 12232619
TI  - Effects of Three Protein Phosphatase Inhibitor on A(23187)-induced Apoptosis of
      HL-60 Cells.
AB  - Calcium ionophore A(23187) could increase the intracellular free Ca(2+)
      concentration and induce apoptosis in some cell lines. In this paper, we reported
      that A(23187) (1 &mgr;g/ml) could induce apoptosis of HL-60 cells after treating
      for 4 hours. Pretreatment with the nontoxic concentration of CsA (0.5 3
      &mgr;g/ml), an inhibitor of the protein phosphatase 2B (PP2B), could prevent
      apoptosis induced by A(23187). Neither okadaic acid (OA, inhibitor of PP1, PP2A,
      PP2C), nor sodium orthovanadate (SoV, inhibitor of tyrosine phosphatase), had
      such effect. The determination of intracellular Ca(2+) with flow cytometry showed
      that CsA did not prevent the increase of intracellular Ca(2+) induced by
      A(23187), which showed that CsA might affect the event in the downstream of
      calcium increase.

PMID- 12232620
TI  - The Expression of Human alpha(1,3) Fucosyltransferase in Human Liver Cancer by in
      situ Hybridization.
AB  - The increase of Lewis x and Sialyl Lewis x epitopes on the surface of cancer
      cells was known for decades. alpha(1,3) FuT is the key enzyme in the biosynthesis
      of these epitopes. The increase of the activity of this enzyme was actually found
      in many cancer tissues, cancer cell lines and the serum of the cancer patients.
      The recent cloning of the enzyme led to the possibility of the application of the
      sensitive methods with small amount of tissues to detect the expression of the
      gene. In this paper, probes for alpha(1,3) FuT type III, V and VI were prepared,
      and they are 447, 486 and 443 bp in length respectively. The DIG-labeled probe
      (type V) was used to detect the mRNA of the enzyme by in situ hybridization.
      Surgical samples from five patients with metastatic lesions, five cases without
      metastasis and two normal liver tissues from liver angioma patients were
      examined. The alpha(1,3) FuT mRNA level was highest in samples with the
      metasitatic lesion, and lowest in normal tissues and those of the original tumor
      lesion in them. The difference is very distinct. The possibility of the method to
      be used in evaluation the prognosis of the disease is discussed.

PMID- 12232621
TI  - The Accumulation of Diacylglycerol and Activation of Protein Kinase C Induced by
      High K(+) Exposure in the Frog Skeletal Muscle.
AB  - The effects of high K(+) exposure on the accumulation of diacylglycerol (DAG) and
      on the activation of protein kinase C (PKC) have been studied in frog skeletal
      muscle. The endogenous DAG increased by treatment with 80 mM K(+) for different
      lengths of time. Correspondingly, high K(+) exposure could induce a translocation
      of PKC. For instance, The membrane-associated PKC activity (pmol/min.g muscle)
      was increased from the control value of 523mmplus;37 to 725mmplus;33 and
      858mmplus;59 after 80 mM K(+) exposure for 2 and 60 minutes, while the cytosolic
      PKC activity was reduced from 543mmplus;35 to 307mmplus; mmplus;20 and
      254mmplus;46, respectively. The accumulation of DAG and the activation of PKC
      induced by high K(+) exposure suggest a possible role of the pathway of DAG/PKC
      in the regulation of the excitation-contraction coupling in skeletal muscle
      fibres.

PMID- 12232622
TI  - A New Computer-imitated Model of Spatial Interaction between Interleukin-2 and
      Interleukin-2 Receptor Complex.
AB  - It is very meaningful to construct the spatial model of ligand-receptor
      interaction between interleukin-2 (IL-2) and interleukin-2 receptor (IL-2R)
      complex for the further studies in the structure-function relationship of IL-2 or
      IL-2R. In our study of the IL-2 molecule, we have found that Glu62 residue takes
      part in the binding to IL-2R alpha subunit and have confirmed that Glu126 residue
      in the residue bound to the IL-2R gamma subunit. In consideration with these
      discoveries and the progress in IL-2R subunits study, we have suggested a new
      model of the spatial interaction between IL-2 and IL-2R.

PMID- 12232623
TI  - A 4.3 Mb YAC Contig in Human Xp11.2: Long-Range Restriction Mapping and
      Identification of CpG Islands.
AB  - The Xp11.2 region o the human X chromosome contains genes involved in a number of
      inherited diseased, with at least one locus that escapes X chromosome
      inactivation, as well as abnormal methylation polymorphism. We isolated a series
      of yeast artificial chromosome (YAC) clones by hybridization screening with DNA
      probes localized within this region and assembled them into a 4.3 Mb contig
      spanning from Xp11.21 to Xp11.23 by a combination of Alu-PCR fingerprinting, STS
      PCR and DNA probe cross hybridization. On the basis of these overlapping YAC
      clones we have constructed the long-range restriction map of this interval and
      placed exactly some DNA markers. Four CpG-dense regions between ARAF1 and OATL2
      were identified based on the long-range restriction mapping, which indicated the
      distribution of genes within this interval. It should assist in the future
      nucleic acid sequence analysis and novel gene identification in this region.

PMID- 12232624
TI  - A Konowledge-based Protein Modeling System and Its Evaluation III. A Sensitive
      Method for Evaluation Protein Model.
AB  - A new scoring table of compatibilities of residues with environments in a protein
      has been derived from environment-dependent amino acid substitution tables. The
      environments of the residues in the 3D structure are described by: (1) the
      secondary structure; (2) the solvent accessibility; (3) the hydrogen bonding. On
      the basis of the scoring table, an assessment method of protein models is
      proposed. Compared with the famous software Profile-3D, The method not only shows
      a more effective test of the accuracy of a 3D protein model, but also exhibits a
      higher sensitivity to the local misfolding. It is an important module in our
      protein modeling system PMODELING.

PMID- 12232625
TI  - Interaction of Colicin E(1) with Lipid Membranes.
AB  - In order to gain an insight into the mechanism of membrane insertion of the pore
      forming protein colicin E(1) and the structure of its membrane-bound form,
      circular dichroism, fluorescence spectroscopy experiments were carried out. The
      results revealed the law of conformational changes by lipid membrane induction of
      the colicin E(1) molecule, and suggest that the lipid membranes with negative
      charges have a strong inducing action on colicin E(1) molecules. With the
      induction of membrane, the colicin E(1) molecules in different conformational
      states can all be recovered to the conformation of membrane insertion in native
      state. The induction intensity of different kinds of lipids on colicin E(1) was
      in the following order: DMPG>DMPE>DMPC. The binding of colicin E(1) with lipid
      vesicles was tight and the membrane-bound proteins were resistant to
      denaturation.

PMID- 12232626
TI  - Changes in Glycosylation Alter the Affinity of the Human Transferrin for Its
      Placental Receptor.
AB  - By using serial lectin-Sepharose affinity chromatography (ConA, DSA, and LCA),
      the transferrins carrying the biantennary complex type of oligosaccharides from
      sera of healthy individuals and those carrying multiantennary oligosaccharides
      from sera of pregnant women were purified. The two kinds of transferrins were
      used to study their binding affinity for isolated placental transferring
      receptor. The results showed that the binding affinity of the highly branched
      transferring decreased to half of that for the biantennary type with a K(d) of
      9.80x10(-8) M as against the latter's 4.97x10(-8) M while the maximum binding
      remains constant. These results suggested that changes in glycosylation altered
      the affinity of the human transferrin for its placental receptor.

PMID- 12232627
TI  - The Construction and Complementary Expression of two TMV Defective Particles in
      Tobacco.
AB  - Two defective mutants of the tobacco mosaic virus (TMV), TMVRP and TMVCP were
      constructed and assembled in vitro. In TMVRP, the 3'-end and part of the TMV coat
      protein (CP) gene was deleted; in TMRCP, most of the replicase genes were
      deleted. These mutant particles were separately or complementally inoculated into
      the tobacco protoplasts by electroporation. The synthesis of TMV coat protein was
      deteted by immuno dot-blot technique at 2 h after inoculation only in those
      complementally infected protoplasts. In addition, using the RT/PCR technique, the
      minus-strand viral RNA of the TMV 3'-end including CP gene was also only detected
      in those protoplasts which were complementally infected with both of the mutant
      particles. The synthesis of the minus-strand RNA started to be detectable at 1h
      after inoculation and it was confirmed by Southern blot analysis.

PMID- 12232628
TI  - Purification of the 28 kD Protein from Maize Pollen and Studies on Its
      Properties.
AB  - A novel protein with ATPase activity was purified from the cytoplasmic extracts
      of maize pollen by acetone precipitation, ammonium sulfate fractionation,
      followed by DEAE-Sephadex A(50) and Mono S ion-exchange chromatography. The
      molecular weight was about 28 kD as determined by SDS-PAGE and the isoelectric
      point was pH 8.3 by IEF-PAGE. Western blotting analysis showed the 28 kD protein
      had no specific immuno-reactions with the anti-kinesin monoclonal or the anti
      dynamin polyclonal antibodies. The maximum ultraviolet absorbance was at 278 nm,
      CD spectrum analysis showed the that 28 kD protein with the feature of a
      globulin. Pharmacological studies indicated that the enzyme activity was strongly
      inhibited by Na(3)VO(4) but insensitive to NEM. It was inhibited about 50% by
      NaF. Oligomycin, KNO(3) and ouabain had no effects on its ATPase activity.

PMID- 12232629
TI  - Expression of Human Bone Morphogenetic Protein 2 in Bombyx mori Larvae and Its
      Purification.
AB  - Recombinant Bm-BacPAK-BMP2 virus which contains the human bone morphogenetic
      protein 2 (BMP2) cDNA gene under the control of polyhedrin gene promoter was
      generated by cotransfection into Bm-N cells with the transfer plasmid pBacPAK
      BMP2 and the modified Bombyx mori nuclear polyhedrosis virus Bm-BacPAK genomic
      DNA. On the fifth day after infection with the recombinant virus, Bombyx mori
      larvae produced about 10 &mgr;g rBMP2 in 1 ml hemolymph. The expressed rBMP2 was
      processed into 16 kD C-terminal fragments and formed 30 kD dimmers with disulfide
      bonds in vivo. The protein was purified to about 90% purity and induced cartilage
      locally in rats 7 days after subcutaneous transplantation.

PMID- 12232630
TI  - The Fusion Expression of HBV preS Epitopes and the Core Antigen.
AB  - The DNA fragments encoding the preS epitopes of HBV surface antigen were fused to
      the HBc gene and expressed in E. coli under the control of the tac promoter. The
      products were analyzed by ELISA and Western blotting, which confirmed that the
      hybrid proteins were expressed as expected. Analysis by electron microscopy and
      CsCl density gradient ultracentrifugation revealed that all fusion proteins were
      able to form particles, only with a slightly lower density than the native
      multimeric HBc. Partially purified fusion particles were then used as immunogen
      to Balb/c mice and high titer antibody against the preS1(21-47) epitope was
      observed, which demonstrated that the immunogenictiy of preS1 (21-47) could be
      greatly improved when fused in the el loop in HBc protein.

PMID- 12232631
TI  - Cloning of the Gene Fragment Encoding the Coenzyme-binding Domain of Yeast ADH I
      and Its Fusion Expression in E. coli.
AB  - In this communication we report the cloning and the over-expression of the
      coenzyme-binding domain of yeast alcohol dehydrogenase. A gene fragment about 400
      bp encoding the NAD binding domain of yeast S. cerevisiae alcohol dehydrogenase I
      was obtained by the PCR method. The domain was expressed as a fusion protein by a
      plasmid which was constructed by inserting the PCR-amplified gene fragment into
      the plasmid pWR590-1 which includes E. coli Lac promoter and a truncated Beta
      galactosidase gene. The fusion protein was characterized by SDS-PAGE and Western
      blot analysis. The yield of the fusion protein was 20% of the total E. coli
      protein.

PMID- 12232632
TI  - Purification and Kinetic Studies of Yeast Alcohol Dehydrogenase I.
AB  - An efficient procedure for the purification of yeast alcohol dehydrogenase I
      (ADHI) was developed. By using Blue-Sepharose 4B affinity chromatography, ADHI
      from yeast (S. cerevisiae) was purified 200-fold with an overall yield of 47% to
      homogeneity as judged by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis and starch gel electrophoresis. Results of studies on the product
      and dead-end inhibition kinetics were in agreement with and ordered Bi Bi
      mechanism as proposed by Wratten and Cleland. Dioxane was found to be a
      competitive inhibitor of this enzyme. The complexity of the reaction mechanism of
      this enzyme is discussed.

PMID- 12232633
TI  - An Unknown Protein Binding Specifically to the Coding Strand of the Estrogen
      Responsive Element.
AB  - An unknown protein, Designated ERE-C-SSBP, which binds to the single coding
      strand of estrogen response element (ERE) tightly and specifically, has been
      discovered unexpectedly during an attempt to establish an ER-ERE gel retardation
      assay with a 13 bp core fragment of the ERE as a probe. Some of its
      characteristics, such as subcellular location, tissue distribution, heat
      stability and relation with divalent metal ions are reported. Interestingly, it
      may be down-regulated by estrogen. Its value in 29 breast carcinoma samples is to
      some degree in reverse correlationship with that of ER. The significance of these
      findings is discussed.

PMID- 12232634
TI  - Affinity Purification of Hepatitis B Virus Surface Antigen Containing PreS1
      Region.
AB  - The large protein of hepatitis B virus surface antigen (LHBs) contained an
      attachment site of HBV to liver cells and the antibodies to preS1 were virus
      neutralizing. Therefore, vaccines containing preS1 would be more protective.
      However, One of the key problems in the preparation of gene-expressed proteins
      was the purification of the products. We have established a method of immuno
      affinity chromatography with the anti-HBsAg-preS1 monoclonal antibody. Using this
      technique, We have successfully purified gene-expressed fusion protein of
      hepatitis B virus surface antigen containing preS1 (21-47). Results showed that
      this method was simple, effective and specific as compared to other methods, and
      might be useful in the future.

PMID- 12232635
TI  - Fluorescence Red-edge-excitation Effects of Human Serum Albumin.
AB  - We have studied the fluorescence red-edge-excitation effects of human serum
      albumin. Our results indicate that the red-edge-excitation effects of human serum
      albumin depend on the pH, temperature and concentration of the denaturant. The
      different red-edge-excitation effects are produced by a redistribution of the
      energy levels both in the ground and the exited states of the chromphore aroused
      by changes of external conditions. Studying red-edge-excitation effects of HAS,
      we have observed that under of acidic pH and high temperature the two denatured
      states of HAS have different conformations, and at pH 7.4 with increasing
      temperature there was a conformation transition process similar to that of acid
      denaturation.

PMID- 12232636
TI  - Purification of Protein Disulfide-isomerase from Human Liver and Preparation of
      Its Antiserum.
AB  - Protein disulfide-isomerase has been isolated from human liver. The preparative
      procedure involved heat treatment, (NH(4))(2)SO(4) precipitation, CM-Sephadex C50
      and DEAE-fast flow chromatography. The enzyme was homogenous and had a molecular
      mass of 60 kD or 120 kD as determined by sodium dodecy1 sulphate electro-phoresis
      and gel filtration respectively, indicating that the enzyme was a 120 kD dimmer
      with a subunit with molecular mass of 60 kD. The enzyme activity was as high as
      830 U/g.protein as measured by the reactivation of "scrambled" ribonuclease. The
      antiserum of high titer was prepared by immunizing New Zealand rabbit with a
      mixture of the protein disulfide-isomerase and adjuvant.

PMID- 12232637
TI  - A Hepatitis B Virus Variant with an Ile to Ser Mutation at aa126 of HBsAg.
AB  - For the detection of HBV variants in patients vaccinated with HBV vaccine but
      failed to be protected, 16 children patients were studied by using the polymerase
      chain reaction (PCR) to amplify the HBV S gene fragment. To increase the
      sensitivity, a nested PCR method was used. These 10 HBV S gene fragments
      amplified from patients were cloned into M13mp18 phage vector and then sequenced
      respectively. One of them, No.19, was found to have a point mutation within a
      determinant coding region (nt524-nt595) of the HBsAg. There was a G at nt 531
      instead of T, leading to a change of Ile to Ser at aa126 of the major HBsAg. As
      aa126 is located in the first loop of the two-looped conformational structure of
      the determinant, and the Ile to Ser at aa 126 is a drastic change, it is
      suggested that the antigenicity of the HBsAg might be altered and the immune
      failure in patient No.19 was probably related to the mutation.

PMID- 12232638
TI  - Growth Promoting Activity of Chimeric Molecules of "Insulin-Insulin-like Growth
      Factor-I" 
AB  - The chimeric molecules of "Insulin-Insulin-like Growth Factor-I", Ins/IGFI(8) and
      Ins/IGF-I(11) were obtained by means of enzymatic semisynthesis. The growth
      promoting activity of these chimeric molecules were evaluated with a mouse
      mammary tumor derived cell line, GR2H6, and compared with that of IGF-I, insulin
      and desoctapeptide insulin (DOI). Both compounds have lower activities than IGF-I
      and effects similar to insulin, but are more potent mitogens than DOI. These
      results indicate that the C-terminus of insulin B-chain is importantly involved
      in its growth promoting activities.

PMID- 12232639
TI  - Characterization of the Insulin and Transferrin Receptors of Two Cancer Cell
      Lines.
AB  - The insulin and transferrin receptors of the PA-1 and GR2H6 cell lines were
      characterized respectively. The optimum pH for the binding of PA-1 cell is 7.0
      with insulin and with transferrin is 7.5 8.0. Scatchard plot and Hill plot
      analysis show respectively the receptor number of 2.97x10(6)/cell and
      6.21x10(7)/cell for insulin receptors of PA-1 and GR2H6 with kD of 4.16x10(-7) M
      and 7.57x10(-7) M, Hill coefficient of 0.78 and 0.82, showing a negative
      cooperativity; transferring receptors of PA-1 and GR2H6 were found to have
      respectively receptor number of 1.25x10(5)/cell and 1.40x10(5)/cell, with kD of
      1.38x10(-9) M and 1.66x10(-8) M. The Hill coefficient was 1.04 and 0.98, almost
      no different from 1, so transferrin receptors showed no cooperativity.

PMID- 12232640
TI  - The Study of a New Type of Membrane for Biosensor.
AB  - Polyvinyl alcohol (PVA) was selected to develop a new type of membrane for
      biosensor. The PVA membrane was first activated by cyanogens bromide, followed by
      coupling with ethyl diamine. After treated by glutaraldehyde, glucose oxidase and
      lactate oxidase were immobilized onto the membrane respectively. Coupled with
      oxygen electrode, the enzyme membrane was used to construct glucose and lactate
      biosensor respectively. The linear range was 5 mg/dl-800 mg/dl for glucose and
      1mg/dl-35 mg/dl for lactate, and the response time of these biosensors was 10
      seconds.

PMID- 12232641
TI  - [Responsibility of the anaesthesiologist in the preoperative risk evaluation].
AB  - Correct indications are essential to perform surgical procedures. However,
      appropriate timing to achieve minimal rates of complications even in high-risk
      patients or major surgery is at the top of the priority list. Perioperative
      responsibility is divided between anaesthesiologists and surgeons. While the
      surgeon is accountable for the surgical procedure, the anaesthesiologist is
      responsible for preoperative risk evaluation, perioperative management, and
      maintenance of vital organ functions. Both of these medical specialities must
      weigh the urgency of the procedure against patient-associated risk factors. Goals
      are optimal patient safety, efficient preoperative evaluation and subsequent
      optimisation to reduce the burden for the health care systems. For most patients
      without underlying diseases, a thorough history and physical examination is
      sufficient. In teaching hospitals, some laboratory results for screening of organ
      function are advisable. Patients can be stratified on clinical grounds into low-,
      medium-, and high-risk categories. Use of these categories, along with
      consideration of the type and urgency of surgery, allows for a reasonable
      approach to preoperative testing. Testing directed towards assessment of organ
      system functional reserve and identification of organs at risk rather than the
      diagnosis of a specific disease, is the primary goal of preoperative evaluation
      prior to surgery. These results are essential to prepare an effective anaesthetic
      plan. Along with increased patient comfort, the number of preoperative hospital
      days can be reduced by outpatient preoperative evaluation clinics.

PMID- 12232642
TI  - [Detection of air embolism by a re-usable Doppler probe integrated in a central
      venous line--application in-vivo].
AB  - PROBLEM: Air embolism frequently occurs under neurosurgical operations performed
      in the sitting position. Recently we reported the idea of inserting a re-usable
      doppler probe into a blind-ending lumen of a central venous catheter (Schregel
      Volk-Catheter, SVC). In vitro testing in a circulation model showed a high
      sensitivity: air bubbles as small as 0.5 microliter were reliably detected at a
      distance up to 4 cm from the tip of the SVC. METHOD: After approval by the local
      ethics committee pigs were anaesthetised and a cardiopulmonary bypass was
      connected. During the bypass period a 12 F SVC (Medex Medical, Germany) with one
      blind-ending lumen was positioned into the proximal vena cava cranialis or vena
      cava caudalis. An 8 MHz doppler probe (MTB Basler, Suisse) was introduced into
      the SVC and connected with the doppler device Multi-Dop T (DWL, Germany). Well
      defined air bubbles (3-6 microliter) were generated by a bubble generator and
      injected into the right femoral vein or the left vena jugularis interna. RESULTS:
      All bubbles were reliably detected by the re-usable doppler probe. Embolic events
      can be documented, counted and quantified by the Multi-Dop T. CONCLUSION: Using
      SVC's with a blind-ending lumen could improve and simplify the detection of air
      embolism. We see several advantages (e.g. sensitivity, costs) compared with
      established methods (precordial doppler, TEE) for detection of air embolism.

PMID- 12232643
TI  - [Precurarization of succinylcholine with cisatracurium: the influence of the
      precurarization interval].
AB  - PURPOSE: To determine the influence of two different pretreatment intervals, i.e.
      3 and 6 min, on the efficacy of 0.01 mg/kg cisatracurium in preventing
      succinylcholine-induced fasciculations and myalgia. METHODS: A total of 60 adult
      patients were randomized and received either 0.01 mg/kg cisatracurium
      (0.2*ED(95)) i.v. (Cis 3 group: pretreatment interval 3 min, Cis 6 group:
      pretreatment interval 6 min) or normal saline i.v. (placebo group) prior to
      injection of succinylcholine. The incidence and severity of fasciculations and
      myalgia and side-effects of precurarization were assessed. RESULTS: The incidence
      of muscle fasciculations was only reduced in the Cis 6 group (45%) compared with
      the Placebo group (85%), p<0.05. Cisatracurium was associated with a higher
      incidence of paralytic symptoms in both pretreatment groups (Cis 3: 75%, Cis 6:
      80%) compared with the Placebo group (30%), p<0.05. CONCLUSION: Cisatracurium is
      only effective in preventing succinylcholine-induced fasciculations when a longer
      pretreatment interval, i.e. 6 min instead of 3 min, is chosen. Precurarization
      led to signs of paralysis in both pretreatment groups in the majority (75-80%) of
      patients without reducing the incidence or severity of postoperative myalgia.

PMID- 12232644
TI  - [Differential diagnosis of left-sided thoracic venous catheters: case report of a
      persistent left superior vena cava].
AB  - The differential diagnosis of left-sided thoracic central venous catheters is
      discussed in context with the cannulation of a persistent left superior vena
      cava. In this case the catheter tip was seen lying to the left of the spine on
      frontal chest X-ray. In addition to the descending aorta, differential diagnoses
      are a persistent left-sided superior vena cava as well as other smaller veins
      such as the left internal thoracic vein, the left superior intercostal vein, or
      the pericardiophrenic vein. The misplacement of a venous catheter in a
      pericardiophrenic vein may result in a fatal pericardial tamponade.

PMID- 12232645
TI  - [Multiorgan failure due to chronic granulomatous disease].
AB  - A 21-year-old male patient developed an acute septic clinical picture with intra
      abdominal abscesses and multiorgan failure. The underlying disease was chronic
      granulomatous disease, an inherited disorder of granulocyte function caused by
      failure of intracellular superoxide production. In spite of surgical procedures
      and a calculated antibiotic and antimycotic therapy, the patient died within a
      few days from septic shock. This case report describes the typical problems of
      patients with a congenital immunodeficiency who grow out of the care of highly
      specialised pediatric-immunological departments.

PMID- 12232646
TI  - [Paracetamol in childhood. Current state of knowledge and indications for a
      rational approach to postoperative analgesia].
AB  - The administration of paracetamol (in the US known as acetaminophen) to children
      and infants for postoperative pain after minor surgery is a well established and
      safe treatment option, if appropriately used. However, if paracetamol is dosed
      according to traditional recommendations (about 20 mg/kg body weight) frequently
      a sufficient analgetic effect cannot be achieved immediately after painful
      interventions. Recently, a higher initial dose (40 mg/kg body weight) was
      suggested for effective postoperative pain control, which seems especially
      important for children after ambulatory anesthesia, but may also be associated
      with certain risks to the patient. Current recommendations also involve
      appropriate timing and route of administration of paracetamol to be most
      effective under different clinical circumstances. In contrast, the risk for liver
      toxicity appears to be very low, if the daily paracetamol dose does not exceed 90
      mg/kg body weight in otherwise healthy children, and if specific risk factors of
      the individual patient are always considered. This review discusses the recent
      publications on pharmacokinetics and -dynamics, the clinical use and dosing, as
      well as the risks and benefits of paracetamol for the treatment of postoperative
      pain in children and infants. Based on this information, specific dosing regimes
      for the postoperative period are suggested for neonates and infants, as well as
      for children in different age groups.

PMID- 12232647
TI  - [The modified technique of continuous suprascapular nerve block. A safe technique
      in the treatment of shoulder pain].
AB  - This study assesses a modified approach for suprascapular nerve block in a single
      shot and continuous catheter technique for the treatment of chronic shoulder
      pain. After thorough anatomic examinations, a new technique was performed in 30
      patients by inserting the catheter into the suprascapular fossa. Complications of
      the technique, time of onset, effect and patient satisfaction were evaluated. The
      results show that there were no complications due to the technique and only one
      patient had a minor VAS score during physiotherapeutic exercise. Local
      inflammation occurred in one patient and dislocation of the catheter in another
      patients. Patient satisfaction (97%) was very high. The modified technique of
      continuous suprascapular nerve block is a safe and easy-to-perform technique in
      the treatment of acute and chronic shoulder pain.

PMID- 12232648
TI  - Safety in anesthesia.
AB  - The specialty of anesthesiology has made extraordinary advances in anesthesia
      safety. Yet, anesthetic mortality and morbidity continue to be far from
      tolerable. Efforts to enhance safety in anesthesia must include adherence to
      explicit and implicit safety standards, must make use of equipment that offers
      modern safety features, must seek to detect and correct developing safety threats
      as early as possible and must have a structured system to analyze problems and to
      institute remedies to prevent their recurrence.

PMID- 12232649
TI  - [Efficient OP management. Suggestions for optimisation of organisation and
      administration as a basis for establishing statutes for operating theatres].
AB  - Economic aspects have gained increasing importance in recent years. The operating
      room (OR) is the most cost-intensive sector and determines the turnover process
      of a surgical patient within the hospital. Thus, optimisation of workflow
      processes is of particular interest for health care providers. If the results of
      surgery are viewed as a product, everything associated with surgery can be
      evaluated analogously to a manufacturing process. All steps involved in producing
      the end-result can and should be analysed with the goal of producing an
      efficient, economical and quality product. The leadership that physicians can
      provide to manage this process is important and leads to the introduction of a
      specialised "OR manager". This position must have the authority to issue
      directives to all other members of the OR team. An OR management subordinates
      directly to the administration of the hospital. By integrating and improving
      management of various elements of the surgical process, health care institutions
      are able to rationally trim costs while maintaining high-quality services. This
      paper gives a short introduction into the difficulties of organising an OR. Some
      suggestions are made to overcome common shortcomings in the daily practise. A
      proposal for an "OR statute" is presented that should be a basis for discussion
      within the OR team. It must be modified according to individual needs and
      prerequisites in every hospital. The single best opportunity for dramatic
      improvement in effective resource use in surgical services lies in the
      perioperative process. The management strategy must focus on process measurement
      using information technology and feed-back implementing modern quality management
      tools.However, no short-term effects can be expected from these changes.
      Improvements take about a year and continuous feed-back of all measures must
      accompany the reorganisation process.

PMID- 12232650
TI  - [Postoperative shivering].

PMID- 12232651
TI  - Treatment of spigelian hernia using totally extraperitoneal laparoscopy
      ambulatory surgery.
AB  - Spigelian hernia is an uncommon hernia of the abdominal wall. Diagnosis and
      treatment are controversial because it is frequently an emergency pathology. We
      report two patients with preoperative diagnosis and treatment using totally
      extraperitoneal laparoscopy under regional anesthesia in a day surgery
      department.

PMID- 12232653
TI  - Safe laparoscopic adhesiolysis with optical access trocar and ultrasonic
      dissection. A prospective study.
AB  - BACKGROUND: The objective of this clinical study was to examine the feasibility,
      safety, and adequacy of hemostasis of combined use of an optical trocar and
      ultrasonic dissection in laparoscopic adhesiolysis in patients with chronic
      abdominal pain. METHODS: In 105 patients, identification of anatomic layers of
      the abdominal wall, establishment of pneumoperitoneum, completeness of
      adhesiolysis, hemostasis, and complications and pain relief were studied.
      RESULTS: All abdominal wall layers could be determined during introduction as
      well as adherence of intraabdominal organs at the introduction site. Ultrasonic
      dissection enables an (almost) complete adhesiolysis in 103 (98%) patients and
      offered adequate hemostasis in 101 (96%) patients. Four perforations during
      laparoscopic adhesiolysis and no late (thermal) perforations were observed.
      CONCLUSIONS: With an optical trocar a safe introduction site of the abdominal
      wall can be chosen. The ultrasonic technique offers a sound adhesiolysis with
      adequate hemostasis and fewer thermal perforations and adds to feasibility and
      safety of laparoscopic adhesiolysis.

PMID- 12232652
TI  - Italian multicenter survey on laparoscopic treatment of gastro-esophageal reflux
      disease in children.
AB  - BACKGROUND: Skepticism is still present today about the laparoscopic treatment of
      gastro-esophageal reflux (GER) in children. We present the prospective experience
      and short-term results of eight Italian pediatric surgical units. METHODS: We
      included all the children with complicated GER, operated after January 1998 by
      single surgeons from eight different centers. Diagnostic aspects, type of
      fundoplication, and complications were considered. All the patients were followed
      for a minimum period of 6 months in order to detect complications or recurrences.
      RESULTS: 288 children were prospectively included. Mean age was 4.8 years (3 m-14
      y). Nissen fundoplication was done in 25%, floppy Nissen in 63%, Toupet in 1.7%,
      and anterior procedures (Lortat Jacob, Thal) in 10%. Gastrostomy was associated,
      if neurological impairment or feeding disorders were present. Mean follow-up was
      15 months and reoperation was necessary in 3.8% of cases. CONCLUSIONS: This
      experience underlines that minimal invasive access surgery in children is safe
      and that the laparoscopic approach is considered in eight centers the golden
      standard for surgical repair of gastro-esophageal reflux disease maintaining the
      same indications and techniques of the open approach.

PMID- 12232656
TI  - Present and future trends in multiple detector-row CT applications: CT
      angiography.

PMID- 12232655
TI  - Multislice helical CT of the abdomen.

PMID- 12232657
TI  - Multidetector-row CT cardiac imaging with 4 and 16 slices for coronary CTA and
      imaging of atherosclerotic plaques.

PMID- 12232658
TI  - CT of acute stroke in the clinical setting.

PMID- 12232659
TI  - Cloning and expression of cyt2Ba7 gene from a soil-isolated Bacillus
      thuringiensis.
AB  - Bacillus thuringiensis ( Bt) cyt genes coding hemolytic and cytolytic toxins
      constitute a gene family, which are divided into two groups: cyt1 and cyt2. A
      novel cyt2 gene was detected from a soil-isolated Bt strain T301, which was
      highly homologous to cyt2Ba1 and finally designated cyt2Ba7. Until now, Cyt2Ba
      has not been expressed alone in Bt or other hosts. In this study, the cyt2Ba7
      gene was cloned into the vector pQE30 and expressed as a fusion protein with
      6xHistidine residues in Escherichia coli. Unlike cyt1A, cyt2Ba7 was freely
      expressed and formed cytoplasmic inclusions without the need for a "helper"
      protein. The 6xHis-tagged Cyt2Ba7 was purified in one step by Ni-NTA affinity
      chromatography, examined cytolytic activity on Sf9 cells, and developed as an
      antigen to obtain the antiserum against Cyt2Ba by subcutaneous injection into
      rabbits. This gene was also cloned into the Bt-E. coli shuttle vector pHT3101 and
      expressed in Bt strain 4Q7. Immunoblotting analysis revealed that the antiserum
      was remarkably selective and specific to Cyt2Ba.

PMID- 12232660
TI  - Physiological alterations and regulation of heterocyst and nitrogenase formation
      in Het(-) Fix(-) mutant strain of Anabaena variabilis.
AB  - Physiological alterations and regulation of heterocyst and nitrogenase formation
      have been studied in Het(-) Fix(-) mutant strain of diazotrophic cyanobacterium
      Anabaena variabilis. Het(-) Fix(-) mutant strain of A. variabilis has been
      isolated by N-methyl-N'-nitro-N"-nitrosoguanidine (NTG) mutagenesis and was
      screened with the penicillin enrichment (500 microg ml(-1)). Growth, heterocyst
      differentiation, nitrogenase and glutamine synthetase (biosynthetic and
      transferase), (14)CO(2)-fixation, nitrate reductase (NR), nitrite reductase
      (NiR), glucose-6-phosphate dehydrogenase (G6PDH), and isocitrate dehydrogenase
      (IDH) activities, and NO(3)(-), NO(2)(-), and NH(4)(+) uptake and whole cell
      protein profile in different metabolic conditions were studied in the Het(-) Fix(
      ) mutant strain taking wild-type A. variabilis as reference. Het(-) Fix(-) mutant
      strain was incapable of assimilating elemental nitrogen (N(2)) due to its
      inability to form heterocysts and nitrogenase and this was the reason for its
      inability to grow in BG-11(0) medium (free from combined nitrogen). In contrast,
      wild-type strain grew reasonably well in the absence of combined nitrogen sources
      and also showed heterocyst differentiation (8.5%) and nitrogenase activity (10.8
      etamol C(2)H(4) formed microg(-1) Chl a h(-1)) in N(2)-medium. Wild-type strain
      also exhibited higher NR, NiR, and GS activities compared to its Het(-) Fix(-)
      mutant strain, which may presumably be due to acquisition of high uptake of
      NO(3)(-), NO(2)(-), and NH(2)(+). Wild-type strain in contrast to its Het(-) Fix(
      ) mutant strain also exhibited high level of G6PDH, IDH, and (14)CO(2) fixation
      activities. Low levels of G6PDH and IDH activities in Het(-) Fix(-) mutant strain
      further confirmed the lack of heterocyst differentiation and nitrogenase activity
      in the Het(-) Fix(-) mutant strain.NR, NiR, and GS activities in both the strains
      were energy-dependent and the energy required is mainly derived from
      photophosphorylation. Furthermore, it was found that de novo protein synthesis is
      necessarily required for the activities of NR, NiR, and GS in both wild-type and
      its Het(-) Fix(-) mutant strain.

PMID- 12232661
TI  - Development of heavy metal-resistant mutants of phosphate solubilizing
      Pseudomonas sp. NBRI 4014 and their characterization.
AB  - Pseudomonas sp. NBRI 4014 is a potent phosphorus solubilizer (284 microg/ml). It
      also produced significant levels of siderophore (143.87 microg/ml) and IAA (5.6
      microg/ml). Siderotyping indicated it was P. aeruginosa siderovar 1. Cadmium (180
      microM), nickel (420 microM), and chromium (370 microM) resistant mutants were
      developed and characterized for their PGPR properties. Mutants were stable under
      non-selective pressure. In cases of nickel and cadmium, there were reductions of
      the siderophore levels. However, they were able to promote root and shoot
      elongation in soybeans ( Glycine max PK 564) at a significant level (p < 0.05) in
      the presence of metals unfamiliar to the wild type. The persistence and stability
      of mutants were evident in rhizospheric soil, thus their exploitation for
      polluted/contaminated sites was supported.

PMID- 12232662
TI  - Telithromycin inhibition of protein synthesis and 50S ribosomal subunit formation
      in Streptococcus pneumoniae cells.
AB  - The new ketolide antibiotic telithromycin (HMR3647) has been examined for
      inhibitory effects in cells of Streptococcus pneumoniae. The antibiotic caused a
      proportional decline in cell growth rate and viability with an IC(50) of 15
      ng/ml. At a concentration of 7.5 ng/ml, protein synthesis in these cells was
      reduced by 50%. As seen in other organisms, this compound was also a very
      effective inhibitor of the formation of the 50S ribosomal subunit in growing
      cells. Pulse and chase labeling assays defined the reduced rate of 50S synthesis
      in antibiotic treated cells. At 7.5 ng/ml the rate was reduced to 50% of the
      control synthesis rate. An IC(50) of 15 ng/ml was found for the effect on this
      process. 30S ribosomal subunit formation was unaffected by the antibiotic.
      Inhibition of translation and 50S particle formation are equivalent targets for
      this antibiotic. The effects of telithromycin in S. pneumoniae are compared with
      those found in Staphylococcus aureus cells.

PMID- 12232663
TI  - Characterization of mycoviruses and analyses of chitinase secretion in the
      biocontrol fungus Metarhizium anisopliae.
AB  - Metarhizium anisopliae is the best-characterized entomopathogen and is used to
      control insect pests in sugar cane plantations in Brazil on a commercial scale.
      We have previously reported the infection of some M. anisopliae strains by dsRNA
      mycoviruses. Here we describe the purification and characterization of the
      viruses (MaV-A1, MaV-M5, MaV-RJ) in terms of dsRNA content, capsid proteins,
      electron microscopy, Western blot, and hybridization patterns. One spontaneous
      mutant lost some of the high molecular weight dsRNA components and showed
      significant alterations in colony morphology and spore production, suggesting
      that viral genes interfere with fungal phenotype. A comparison between dsRNA
      mycovirus-free and infected M. anisopliae isolates showed that virus-free
      isolates have increased endochitinase secretion. By comparing the following
      parameters: the buoyant density in CsCl of the presumed virions; the number and
      estimated molecular weight of the dsRNA components and the molecular mass of the
      capsid proteins to other mycoviruses previously described, we suggest the
      inclusion of MaV-A1 and MaV-M5 in the family Totiviridae and MaV-RJ in the family
      Partitiviridae.

PMID- 12232664
TI  - Amino acid deamination by ruminal Megasphaera elsdenii strains.
AB  - When ruminal fluid from a cow fed timothy hay was serially diluted (10-fold
      increments into anaerobic broth containing 15 mg ml(-1) Trypticase), the low
      dilutions (< or =10(-6)) had optical densities greater than 2.0 and ammonia
      concentrations greater than 100 m M. The optical densities and ammonia
      concentrations of the 10(-8) and 10(-9) dilutions were very low, but large cocci
      were observed in the 10(-8) dilution. The large cocci were isolated and
      identified by 16S rDNA sequencing as Megasphaera elsdenii. The freshly isolated
      strain (JL1) grew well on Trypticase, but less than 4% of the amino acid nitrogen
      in Trypticase was converted to ammonia. Optical density and ammonia production
      were twice as great if Casamino acids were provided, and similar results were
      obtained with seven other strains (B159, AW106, YT91, LC1, T81, J1, and YZ70).
      Specific activities of deamination (based on Casamino acids) of the eight strains
      ranged from 100 (strain JL1) to 325 (strain B159) nmol mg protein(-1) min(-1).
      None of the strains could utilize branched-chain amino acids as an energy source
      for growth, but specific activities of branched-chain amino acid deamination
      ranged from 15 to 65 nmol mg protein(-1) min(-1). All eight of the M. elsdenii
      strains grew well in the presence of 5 micro M monensin, and only two of the
      strains were strongly inhibited by 20 micro M monensin. On the basis of these
      results, it appears that M. elsdenii is deficient in peptidase activity and can
      utilize only a few amino acids. Some M. elsdenii strains produced ammonia and
      branched-chain volatile fatty acids nearly as fast as obligate amino acid
      fermenting ruminal bacteria, but the extent of this production was at least
      fourfold lower. Because all of the strains could tolerate 5 micro M monensin, it
      is unlikely that this feed additive would significantly inhibit M. elsdenii in
      vivo.

PMID- 12232665
TI  - Bioremediation of an industrial effluent containing monocrotophos.
AB  - Almost 30% of the precious agricultural output of India is lost owing to pest
      infestation. In India, pesticide consumption for protecting crops is about 3% of
      the total world consumption. Monocrotophos (MCP), an organophosphorus
      insecticide, is widely used to control insects on crops. Being readily water
      soluble and highly toxic, its removal from wastewater generated during
      manufacture becomes inevitable. Bioremediation of wastewater containing MCP by
      Arthrobacter atrocyaneus, Bacillus megaterium, and Pseudomonas mendocina was
      highest at pH 8.0, but maximum reduction in Chemical Oxygen Demand (COD) was at
      pH 7.0. Removal of MCP and reduction in COD by B. megaterium and Ps. mendocina
      were highest at 35 degrees C, while with A. atrocyaneus, it was maximum at 30
      degrees C, under aerated culture condition and inoculum density of 10(8)
      cells/ml. Use of pure cultures for bioremediation of effluent containing MCP
      appears to be the first such attempt.

PMID- 12232666
TI  - Transcription levels of Pseudomonas aeruginosa exotoxin a gene and severity of
      symptoms in patients with otitis externa.
AB  - Polymerase chain reaction (PCR)-based detection and transcription of the gene
      encoding a potent virulence factor, the exotoxin A, were done on 32 isolates of
      Pseudomonas aeruginosa belonging to 23 genotypes. These isolates were obtained
      from 22 patients who were admitted to the emergency room in a medical center
      during a 5-month period with the diagnosis of either unilateral or bilateral
      otitis externa. Patients showed symptoms that ranged from mild to severe. PCR
      amplification of a 396-bp fragment of the gene encoding the exotoxin A was done
      on extracted DNA. Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) was
      performed on extracted RNA to detect exotoxin A gene mRNA transcripts.
      Quantitation of RT-PCR amplicons from P. aeruginosa isolates associated with mild
      and severe symptoms was determined by end-point titration of c-DNA and scanning
      of amplicons with the Storm Gel and Blot Imaging System. Data have shown that all
      of the 32 isolates of P. aeruginosa carry the exotoxin A gene, and all isolates
      with the exception of two had the exotoxin A transcription demonstrated by the
      production of a 396-bp amplicon from RT-PCR-amplified RNA. The remaining two
      isolates amplified fragments that were slightly smaller than the expected size.
      Additional studies are needed to characterize these two mRNA transcripts.
      Transcription levels of exotoxin A gene associated with severe symptoms were
      significantly more elevated than those associated with mild to moderate symptoms.
      Studies are under way to determine expression of P. aeruginosa exotoxin A by
      detecting quantitatively levels of the translated exotoxin A protein produced by
      isolates associated with severe and mild to moderate symptoms.

PMID- 12232667
TI  - A conserved Ala320 in the FtsZ of Porphyromonas gingivalis is important for cell
      division.
AB  - We have previously cloned the gene encoding the cell division protein FtsZ,
      designated PgFtsZ, from Porphyromonas gingivalis, an oral anaerobic bacterium
      implicated in advanced periodontal disease. In the present study, we have shown
      that overexpression of ZDeltaC02, a mutant form of PgFtsZ in which 128 amino acid
      residues have been removed from the C-terminus, caused an inhibition of cell
      division in E. coli cells. However, overexpression of ZDeltaC03, missing 177
      residues from the C-terminus, did not inhibit cell division, suggesting that the
      49 residues between 281 and 329 are required for cell division. Sequence
      comparison of the known prokaryotic FtsZs revealed that this region contained a
      highly conserved domain, designated A-domain, in which Ala320 of PgFtsZ was
      conserved throughout a broad variety of species. Therefore, we analyzed the role
      of Ala320 by site-directed mutagenesis. We found that overexpression of ZA320H
      and ZA320R resulted in the normal phenotype, unlike the wild type. Immunoblot
      analysis showed that these mutant proteins were expressed at similar levels.
      These results suggest that Ala320 is highly conserved and is crucial for cell
      division.

PMID- 12232668
TI  - Efficient electrotransformation of corynebacterium diphtheriae with a mini
      replicon derived from the Corynebacterium glutamicum plasmid pGA1.
AB  - Efficient transformation of the human pathogen Corynebacterium diphtheriae was
      achieved with novel cloning vectors consisting of a mini-replicon from the
      cryptic C. glutamicum plasmid pGA1 as well as of the aph(3')-IIa or tetA(Z )
      antibiotic resistance genes. Plasmid-containing transformants of C. diphtheriae
      were recovered at frequencies ranging from 1.3 x 10(5) to 4.8 x 10(6) colony
      forming units (cfu)/microg of plasmid DNA. Vector DNA was directly transferred
      from Escherichia coli into C. diphtheriae with frequencies up to 5.6 x 10(5)
      cfu/microg of plasmid DNA. On the basis of the pGA1 mini-replicon, an expression
      vector system was established for C. diphtheriae by means of the P(tac) promoter
      and the green fluorescent reporter protein. In addition, other commonly used
      vector systems from C. glutamicum, including the pBL1 and pHM1519 replicons, and
      the sacB conditionally lethal selection marker from Bacillus subtilis, were shown
      to be functional in C. diphtheriae. Thus, the ability to apply the standard
      methods of C. glutamicum recombinant DNA technology will greatly facilitate the
      functional analysis of the recently completed C. diphtheriae genome sequence.

PMID- 12232669
TI  - Effect of drought on the growth and survival of the stress-tolerant bacterium
      Rhizobium sp. NBRI2505 sesbania and its drought-sensitive transposon Tn 5 mutant.
AB  - Studies were conducted to elucidate the nature of drought tolerance in the
      bacterium Rhizobium sp. NBRI2505 sesbania and its transposon Tn 5 induced mutant
      to assess the role of salt, pH, and temperature stresses in contributing to
      drought tolerance, and to correlate drought tolerance and symbiotic
      effectiveness. Rhizobium sp. NBRI2505 sesbania tolerated yeast extract mannitol
      broth (YEB) containing 28% salt (NaCl; wt/vol) for up to 18 h of incubation at 30
      degrees C, survived a 2-h incubation in YEB at 65 degrees C, and when subjected
      to drought stress, tolerated YEB containing 45% polyethylene glycol 6000 (PEG;
      wt/vol) for up to 5 days of incubation at 30 degrees C. One drought-sensitive
      mutant Rhizobium sp. NBRI2505 sesbania T112 (T112) containing a single Tn 5
      insertion was selected after screening about 10,000 clones. T112 was specifically
      defective in its tolerance for drought: when subjected to drought stress, it
      tolerated YEB containing 45% PEG for up to 2 days of incubation at 30 degrees C.
      T122 mutant was also more sensitive to the heat and desiccation stresses,
      compared with Rhizobium sp. NBRI2505 sesbania in the presence of 45% PEG. Our
      results demonstrated a positive effect of calcium on the survival of Rhizobium
      sp. sesbania under acidic stress conditions. The observed enhanced survival at pH
      3 of Rhizobium sp. NBRI2505 sesbania and T112 in the presence of 5% CaCO(3)
      suggests the requirement of calcium for growth and survival, which may have an
      ecological significance in acidic soils. Mutant strain T112 produced ineffective
      symbiosis with the plant host in the presence of 2.5 and 5% PEG, indicating that
      drought tolerance is required for effective symbiosis.

PMID- 12232670
TI  - Molecular cloning and characterization of nodD genes from Rhizobium sp. SIN-1, a
      nitrogen-fixing symbiont of Sesbania and other tropical legumes.
AB  - Rhizobium sp. SIN-1, a nitrogen-fixing symbiont of Sesbania aculeata and other
      tropical legumes, carries two copies of nodD, both on a sym plasmid. We have
      isolated these two nodD genes by screening a genomic library of Rhizobium sp. SIN
      1 with a nodD probe from Sinorhizobium meliloti. Nucleotide sequence and the
      deduced amino acid sequence analysis indicated that the nodD genes of Rhizobium
      sp. SIN-1 are most closely related to those of R. tropici and Azorhziobium
      caulinodans. Rhizobium sp. SIN-1 nodD1 complemented a S. meliloti nodD1 D2 D3
      negative mutant for nodulation on alfalfa, but failed to complement a nodD1
      mutant of S. fredii USDA191 for soybean nodulation. A hybrid nodD gene,
      containing the N-terminus of S. fredii USDA191 nodD1 and the C-terminus of
      Rhizobium sp. SIN-1 nodD1, complemented the nodD1 negative mutant of USDA191 for
      nodulation on soybean.

PMID- 12232671
TI  - Minimally invasive radiologically guided intervention for the treatment of
      salivary calculi.
AB  - PURPOSE: To describe the technique and examine the value of salivary stone
      extraction using a minimally invasive, radiologically guided approach as an
      alternative to salivary gland surgery for the treatment of benign salivary gland
      obstruction. METHODS: Eighty-six cases of sialolithiasis (83 patients) were
      treated by stone removal using a Dormia basket under local anesthesia and
      fluoroscopic guidance. Postoperative assessment was made clinically at review, by
      sialogram and by questionnaire. RESULTS: Of 86 cases of sialolithiasis treated,
      in 55 (64%) it was possible to remove all stones. In 12 cases (14%) part of a
      stone or some of a number of calculi were removed and in 19 cases (22%) the
      procedure failed. The commonest reason for failure was fixation of the stone
      within the duct. Symptoms at review (range 1-49 months, mean 17 months) were
      relieved in 55 of 67 (82%) of cases where a stone or portion of stone was
      removed. CONCLUSIONS: Stone removal from the salivary duct system by
      radiologically guided, minimally invasive approach is a simple procedure with low
      morbidity and high patient acceptance when appropriate selection criteria are
      applied. These criteria are considered and recommendations made.

PMID- 12232672
TI  - Balloon dilatation of salivary duct strictures: report on 36 treated glands.
AB  - PURPOSE: This paper describes the technique for balloon dilatation of salivary
      duct strictures and evaluates the clinical and radiographic findings in a
      consecutive series of 36 affected glands. METHODS: Thirty-four patients (36
      glands) had balloon dilatation of their salivary duct strictures performed under
      fluoroscopic control. They were evaluated immediately afterwards and at review by
      sialography. RESULTS: In 36 cases attempted, 33 (92%) strictures were dilated.
      The immediate post-treatment sialogram was available in 28 cases, of which 23
      (82%) demonstrated complete and four (14%) partial elimination of stricture. In
      one case the appearance was unchanged (4%). Review data (mean 6.8 months) were
      available on 25 glands: 12 were asymptomatic (48%), 12 (48%) had reduced symptoms
      and one (4%) failed to improve. Sialographic data were available on 21 glands: in
      10 (48%) the duct remained patent, in one (5%) the stricture was partially
      eliminated, in seven (33%) the strictures had returned and in the remaining three
      (14%) cases there was complete obstruction. CONCLUSIONS: Balloon dilatation is an
      effective treatment of salivary duct stenosis. In half the cases the stricture
      recurred but symptomatic improvement was achieved and maintained in the majority
      of cases.

PMID- 12232673
TI  - Multilineage differentiation of adult human bone marrow progenitor cells
      transduced with human papilloma virus type 16 E6/E7 genes.
AB  - We have established a new adult human bone marrow-derived cell line hMPC 32F,
      stably transduced with human papilloma virus type 16 E6/E7 genes, that displays
      mesenchymal multilineage differentiation ability in vitro. The hMPC 32F cells
      exhibited a population doubling time of 22 h and have been maintained in culture
      for about 20 passages. When cultured in conditions promoting osteogenic,
      adipogenic, or chondrogenic differentiation, hMPC 32F cells expressed mature
      differentiated phenotypes. These include (1) osteoblastic phenotype characterized
      by upregulated alkaline phosphatase (ALP) expression and extracellular matrix
      mineralization, (2) adipocytic phenotype with the presence of intracellular lipid
      droplets, and (3) chondrocytic phenotype of round cells surrounded by a sulfated
      proteoglycan-rich matrix. In addition, the hMPC 32F cells expressed
      differentiation lineage-specific genes, as detected by RT-PCR. Furthermore,
      osteogenic and adipogenic cultures responded to regulatory factors such as
      transforming growth factor-beta1 (TGF-beta1) and 1alpha, 25-dihydroxyvitamin D3
      (1,25(OH)2D3). Thus, continuous treatment of osteogenic cultures for 2 weeks with
      TGF-beta1 decreased ALP activity and mRNA expression and inhibited osteocalcin
      mRNA expression and matrix mineralization, whereas l,25(OH)2D3 had an additive,
      stimulatory effect. In adipogenic cultures, treatment with TGF-beta1 for 2 weeks
      markedly inhibited adipogenesis whereas 1,25(OH)2D3 had no obvious effect.
      Finally, clonal analysis of hMPC 32F cells revealed a high percentage of
      multipotent clones, although clones of more restricted differentiation potential
      were also present. These characteristics of the hMPC 32F cell line suggest their
      pluripotent, progenitor, and nontransformed nature and indicate their potential
      application for studying the mechanisms governing developmental potential of
      adult human bone marrow mesenchymal progenitor cells.

PMID- 12232674
TI  - Differential localization of myosin II isoforms in resting and activated
      osteoclasts.
AB  - Osteoclasts resorb bone through a cyclical process of attachment to matrix,
      polarization, retraction, and migration. Although this process requires major
      alterations in the organization of actin structures, little is known about roles
      that myosins play in osteoclast cytoskeletal dynamics. We performed
      immunolocalization of myosin II using antibodies against heavy chain isoforms IIA
      and IIB and found that osteoclasts expressed the isoforms in distinct subcellular
      locations. Myosin IIA was enriched in dynamic cytoskeletal compartments,
      including the sealing zones of polarized and unpolarized osteoclasts. In
      contrast, myosin IIB was generally absent from these regions and maintained a
      comparatively static distribution during different phases of the osteoclast
      activation cycle. Inhibition of myosin II in osteoclasts by treatment with 2,3
      butanedione monoxime caused detachment of unpolarized, but not polarized, cells
      from the bone matrix. These results suggest that myosin IIA is critical to
      development of an activated osteoclast phenotype.

PMID- 12232675
TI  - Osteoblast-mediated mineral deposition in culture is dependent on surface
      microtopography.
AB  - Osteoblast phenotypic expression in monolayer culture depends on surface
      microtopography. Here we tested the hypothesis that mineralized bone nodule
      formation in response to osteotropic agents such as bone morphogenetic protein-2
      (BMP-2) and dexamethasone is also influenced by surface microtopography. Fetal
      rat calvarial (FRC) cells were cultured on Ti implant materials (PT [pretreated],
      Ra = 0.6 microm; SLA [course grit blasted and acid etched], Ra = 4.0 microm; TPS
      [Ti plasma sprayed], Ra = 5.2 microm) in the presence of either BMP-2 (20 ng/ml)
      or 10(-8) M dexamethasone (Dex). At 14 days post-confluence, a homogenous layer
      of cells covered the surfaces, and stacks of cells that appeared to be nodules
      emerging from the culture surface were present in some areas on all three Ti
      surfaces. Cell proliferation decreased while alkaline phosphatase specific
      activity (ALPase) and nodule number generally increased with increasing surface
      roughness in both control and treated cultures. There was no difference in cell
      number between the control and Dex-treated cultures for a particular surface, but
      BMP-2 significantly reduced cell number compared with control or Dex-treated
      cultures. Treatment with Dex or BMP-2 further increased ALPase on all surfaces
      except for PT cultures with Dex. Dex had no effect on nodule area in cultures
      grown on PT or SLA disks, yet increased nodule number by more than 100% in
      cultures on PT disks. Though the effect of BMP-2 on nodule number was the same as
      Dex, BMP-2 increased nodule area on all surfaces except TPS, where area was
      decreased. Ca and P content of the cell layers in control cultures did not vary
      with surface roughness. However, cultures treated with Dex had increased Ca
      content on all surfaces, but the greatest increase was seen on SLA and TPS. BMP-2
      increased Ca content in cultures on all surfaces, with the greatest increase on
      the PT surface. BMP-2 treatment increased P content on all surfaces, whereas Dex
      only increased P on rough surfaces. Of all cultures examined, the Ca/P weight
      ratio was 2:1 only on rough surfaces with BMP-2, indicating the presence of bone
      like apatite. This was further validated by Fourier transform infrared (FTIR)
      imaging showing a close association between mineral and matrix on TPS and SLA
      surfaces with BMP-2-treated cells, and individual spectra indicated the presence
      of an apatitic mineral phase comparable to bone. In contrast, mineral on the
      smooth surface of BMP-2-treated cultures and on all surfaces where cultures were
      treated with Dex was not associated with the matrix and the spectra, not typical
      of bone apatite, implying dystrophic mineralization. This demonstrates that
      interactions between growth factor or hormone and surface microtopography can
      modulate bone cell differentiation and mineralization.

PMID- 12232676
TI  - Differences in sialic acid residues among bone alkaline phosphatase isoforms: a
      physical, biochemical, and immunological characterization.
AB  - High-performance liquid chromatography (HPLC) separates three human bone alkaline
      phosphatase (BALP) isoforms in serum; two major BALP isoforms, B1 and B2, and a
      minor fraction, B/I, which is composed on average of 70% bone and 30% intestinal
      ALP. The current studies were intended to identify an in vitro source of the BALP
      isoforms for physical, biochemical, and immunological characterizations. The
      three BALP isoforms were identified in extracts of human osteosarcoma (SaOS-2)
      cells, by HPLC, after separation by anion-exchange chromatography. All three BALP
      isoforms were similar with respect to freeze-thaw stability, solubility, heat
      inactivation, and inhibition by L-phenylalanine, L-homoarginine, and levamisole.
      The isoforms were also kinetically similar (i.e., maximal velocity and KM at pH
      8.8 and pH 10.0). The isoforms differed, however, with respect to sensitivity to
      precipitation with wheat germ agglutinin (WGA), P < 0.001, but not Concanavalin
      A. At 3.0 mg/ml, WGA precipitated approximately 25% of B/I but more than 80% of
      B1 and B2. Molecular weights were estimated by native gradient gel
      electrophoresis: B/I, 126 kDa; B1, 136 kDa; and B2, 141 kDa. Desialylation with
      neuraminidase reduced the apparent sizes of B1 and B2 to 127 kDa (i.e.,
      approximately to that of B/I). The total carbohydrate content was calculated to
      be 18 kDa, 28 kDa, and 33 kDa (i.e., 14%, 21%, and 23%) for the BALP isofonns,
      B/I, B1, and B2, respectively. The number of sialic acid residues was estimated
      to be 29 and 45, for each B1 and B2 homodimer, respectively. Apparent
      discrepancies between these estimates of molecular weight and estimates based on
      gel filtration chromatography were attributed to nonspecific interactions between
      carbohydrate residues and the gel filtration beads. All three BALP isoforms
      showed similar dose-dependent linearity in the commercial Alkphase-B and Tandem
      MP Ostase immunoassays, r = 0.944 and r = 0.985, respectively (P < 0.001). In
      summary, our data indicate that B1 and B2 have more (or more reactive) sialic
      acid residues compared with B/I, which mainly explains the apparent differences
      in molecular weight. Future investigations will focus on the clinical and
      functional significance of the revealed differences in sialic acid residues.

PMID- 12232677
TI  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces the
      osteoblastic differentiation of the human osteosarcoma cell line SaOS-2.
AB  - The Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) is a hematopoietic
      growth factor that regulates the in vitro and in vivo proliferation and
      differentiation of hematopoietic cells through the interaction with a specific
      heterodimeric receptor complex (GM-CSFR), consisting of an alpha and a beta chain
      with molecular weights of 80 and 120 KDa, respectively. We have studied the
      expression of the GM-CSFR (alpha chain) on the surface of the human osteosarcoma
      cell line SaOS-2 and the in vitro effects of different concentrations (10, 100,
      and 200 ng/ml) of GM-CSF on GM-CSFR expression and the biological activity of
      SaOS-2 cells. Our data show that SaOS-2 cells express GM-CSFR and that GM-CSF can
      down-regulate the expression of its own receptor on these cells. Furthermore, to
      evaluate the biological effects of GM-CSF on SaOS-2 cells, we have investigated
      cell proliferation and differentiation of these cells treated with different
      doses of the growth factor through: (1) a morphological analysis of typical
      osteoblast differentiation markers such as osteopontin and BSP-II; (2)
      measurement of alkaline phosphatase (ALP) activity; (3) production of bone ECM
      components (collagen I, fibronectin, tenascin, and laminin); (4) production of
      interleukin-6 (IL-6) and osteocalcin in the culture medium. The results show that
      the in vitro treatment of SaOS-2 cells with recombinant human GM-CSF causes a
      decreased cell proliferation and an increased production of osteopontin, BSP-II,
      ALP, IL-6, and most but not all ECM components. These findings suggest that GM
      CSF can regulate proliferation and differentiation of osteoblast-like SaOS-2
      cells and could also play an unexpected role in the maturation of bone tissue.

PMID- 12232678
TI  - Collagen Ialpha1 polymorphism is associated with bone characteristics in
      Caucasian children and young adults.
AB  - A large proportion of the variation in bone mass can be explained by genetic
      factors. We analyzed the G to T substitution in the Sp1 binding site in the first
      intron of the collagen type Ialpha1 (COLIA1) gene in relation to bone mass. The
      genotypes GG, GT, and TT were determined in 148 Caucasian children and young
      adults. We performed dual energy X-ray absorptiometry twice (mean follow-up time
      4.4 years), and speed of sound (SOS) was assessed by tibial ultrasonometry at
      follow-up. Genotype distribution was 104 (70%) GG, 40 (27%) GT and 4 (3%) TT.
      Carriers of the T-allele had a 0.5 SDS (standard deviation score) decreased bone
      mineral content (BMC) of total body (P = 0.001), and a 0.4 SDS decreased bone
      mineral density (BMD) for both lumbar spine (P = 0.04) and total body (P = 0.05).
      The genotype effect on BMD and BMC decreased after adjustment for height or body
      mass index. When we calculated apparent BMD, these differences diminished to 0.1
      SDS and were no longer significant. T-allele carriers had shorter stature (0.4
      SDS; P = 0.04) and smaller bones (0.5 SDS lower width of the lumbar vertebral
      body; P = 0.01). The T-allele was also associated with lower SOS (P = 0.03),
      independent of BMD and BMC, and lower lean body mass. Similar associations were
      found at follow-up. The change in BMD and BMC SDS between the first and second
      measurement did not differ between the GG and GT&TT group. In conclusion, the
      COLIA1 polymorphism in children and young adults is associated with several bone
      characteristics. However, at least a part of the COLIA1 effect on bone mass may
      be related to differences in frame size.

PMID- 12232679
TI  - Association of a common allelic polymorphism (C677T) in the methylene
      tetrahydrofolate reductase gene with a reduced risk of osteoporotic fractures. A
      case control study in Danish postmenopausal women.
AB  - Twin studies indicate a substantial genetic component in the development of
      osteoporosis. One of the latest studied candidate genes is the one coding for
      methylene tetrahydrofolate reductase (MTHFR) (C677T) in which a point mutation
      gives rise to a thermolabile variant of MTHFR. The aim of this study was to
      investigate the influence of this mutation on peripheral measures of bone density
      and on the odds ratios (OR) for hip and lower forearm fracture in a case control
      study of Danish postmenopausal women. A total of 74 women with lower forearm
      fracture, 41 women with hip fracture, and 207 age-matched controls were included.
      All had broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured
      at the heel as well as bone mineral density (BMD) measured by dual X-ray
      absorptiometry at the distal forearm. The MTHFR (C677T) genotypes were determined
      using polymerase chain reaction restriction fragment length polymorphism (PCR
      RFLP). Only 2 of 21 individuals with the TT genotype had sustained a fracture as
      opposed to 46 of 142 with the CT genotype and 67 of 159 with the CC genotype (P =
      0.007). Using logistic regression, the following odds ratios were found when
      comparing the individuals homozygotic for the C-allele with those homozygotic for
      the T-allele: lower forearm fracture OR = 3.93 (1.25; 12.40, P = 0.02), hip
      fracture OR = 6.99 (l.35; 36.92, P = 0.02) and the fractures combined OR = 4.33
      (1.73; 10.81, P = 0.002). In this study, the MTHFR (C677T) genotypes were not
      significantly associated with BMD at the lower forearm or with ultrasound
      parameters measured at the calcaneus. However, a significant increase in the odds
      ratio of fracture was found for the wild-type C-allele.

PMID- 12232680
TI  - Isolation of human osteoclasts formed in vitro: hormonal effects on the bone
      resorbing activity of human osteoclasts.
AB  - Osteoclasts are multinucleated cells that carry out bone resorption. Analysis of
      the direct effect of hormones on the bone-resorbing activity of human osteoclasts
      has been limited by difficulties in isolating these cells from the human
      skeleton. In this study, human osteoclasts formed from cultures of peripheral
      blood mononuclear precursors (PBMCs) on a Type-I collagen gel were isolated by
      collagenase treatment for investigating their resorptive activity. PBMCs were
      cultured in the presence of M-CSF, soluble RANKL, dexamethasone, and 1,25(OH)2D3.
      The isolated multinucleated cells expressed the osteoclast markers, TRAP, VNR,
      cathepsin K, calcitonin receptors and were capable of extensive lacunar
      resorption. Calcitonin inhibited the motility and resorptive activity of
      osteoclasts. RANKL significantly stimulated osteoclast resorption, but
      1,25(OH)2D3, PTH, and OPG did not. These findings indicate that calcitonin and
      RANKL act directly on human osteoclasts to inhibit and stimulate osteoclast bone
      resorbing activity, respectively, and that PTH, 1,25(OH)2D3, and OPG are more
      likely to influence osteoclast activity indirectly. This technique of human
      osteoclast isolation should permit the effects of cellular and hormonal/humoral
      factors on the bone-resorbing activity of mature human osteoclasts to be assessed
      independently of any effect such factors have on osteoclast formation. It should
      also make it possible to examine directly the resorptive activity and other
      characteristics of osteoclasts in specific bone disorders such as Paget's
      disease.

PMID- 12232681
TI  - Bone and celiac disease.
AB  - Celiac disease is an intestinal disease due to an abnormal immuno-mediated
      response to gluten and other peptides from different cereals in genetically
      susceptible subjects. Several systemic alterations, including bone alterations,
      may be present in affected subjects. Once considered rare, it is now known to be
      quite frequent in both Europe and North America, as the recent availability of
      specific serological markers has drastically changed our perspective on its
      prevalence. The diagnosis of celiac disease may be very difficult because the
      clinical picture is highly variable and the characteristic intestinal signs and
      symptoms may be completely absent. Among the extra-intestinal alterations, bone
      mass decrease and bone metabolism derangement are frequently present and can be
      the only signs of an otherwise silent celiac disease. Clinical and
      epidemiological data are now plentiful but no conclusive data on the pathogenesis
      of bone involvement in celiac disease are available yet. Bone alterations were
      once thought to derive from calcium and vitamin D deficiency secondary to simple
      intestinal malabsorption, but now a more complex interaction between cytokines
      and local/systemic factors influencing bone formation and reabsorption is
      envisaged, Also, there is now substantial evidence supporting a lifelong gluten
      free diet as the first-choice therapy for celiac disease, and as far as we know,
      this is the only effective measure to restore bone metabolism to an apparent
      normality. In the young, an early-started gluten-free diet can even lead to a
      satisfactory recovery of bone mass. In adults, however, there is no spontaneous
      recovery, and there are no conclusive data on the efficacy of standard therapies
      for osteoporosis in reducing the fracture risk. For these reasons, we feel that a
      review of the clinical findings on bone problems in celiac disease may be useful
      for both gastroenterologists and osteoporosis specialists.

PMID- 12232682
TI  - Is time since hip fracture influencing the discrimination between fractured and
      nonfractured subjects as assessed at the calcaneum by three technologically
      different quantitative ultrasound devices?
AB  - Because quantitative ultrasound (QUS) instruments from different manufacturers
      have significant technical differences, it is difficult to assess whether all of
      them can discriminate similarly between osteoporotic fractures and age-matched
      controls. Thus, to avoid any bias, reliable comparative assessment of the QUS
      devices should be carried out on the same population. Few studies have fulfilled
      this condition. Another source of variability in cross-sectional studies in which
      fractured and nonfractured subjects are compared is the time since osteoporotic
      fracture. Our study evaluated the ability of three calcaneal QUS devices to
      discriminate patients with osteoporotic hip fracture from control subjects, using
      the same population. In addition, a subset of patients was re-measured about 9
      months after the hip replacement surgery to check how the time since fracture
      affects the discriminatory ability of the different QUS devices. Fifty
      postmenopausal hip-fractured patients and 46 postmenopausal age-matched controls
      were included in this study and measured on three QUS devices, as well as 50
      young healthy controls to calculate the T-score. Odds ratio results showed that a
      decrease in UBIS trade mark BUA of 1 SD was associated with a significant
      increase in fracture risk (odds ratio adjusted = 2.30) comparable with Sahara
      broadband ultrasound attenuation (BUA) (OR adj. = 2.30), and Achilles BUA (OR
      adj. = 3.5). However, given the large overlap between the 95% intervals of each
      OR and for the areas under ROC curves, no significant difference was found
      between them. In the subset of 15 hip-fractured subjects, no significant
      differences were found between ultrasound parameters of the first visit and 9
      months after except for the heel width (soft tissue variation). Odds ratio and
      areas under the curve (AUC) tend to increase from visit 1 to 2 for the BUA and
      decrease substantially for the SOS for all but the Lunar Achilles+.
      Nonsignificant correlation was found between the absolute difference of the
      ultrasound parameters measured at the two visits and the time since fracture,
      except for the Sahara SOS (r = 0.45; P < 0.04). In conclusion, no significant
      differences between QUS technologies were observed in their positive and
      significant ability to discriminate hip-fractured patient from controls. However,
      this statement is shadowed when taking into account the time since fracture which
      seems to negatively influence results obtained on dry versus wet QUS systems. As
      a result, it is advisable that such parameters would be taken into account when
      designing a study aimed to demonstrate the discriminatory ability of heel
      ultrasound between normal and hip-fractured patients.

PMID- 12232683
TI  - In vitro mechanical and cellular responses of neonatal mouse bones to loading
      using a novel micromechanical-testing device.
AB  - Mechanical stimulation is critical for the maintenance of bone architecture and
      bone mass. These effects are dependent on the magnitude, duration, and rate of
      the mechanical stimuli. The goals of the present study were to develop and
      optimize a micromechanical-testing device for in vitro mechanical stimulation of
      whole viable bones, and to identify the physical parameters of loading that
      elicit maximal anabolic responses. The model was the 7-8-day-old neonatal CD-1
      mouse tibia. A range of cyclic strain magnitudes [500-7000 microstrain
      (microstrain)] and frequencies [0.2-30 hertz (Hz)] were applied to the neonatal
      bones. Incremental cyclic compression tests showed that the bones were
      nonlinearly viscoelastic. Bone stiffness and hysteresis energy dissipation were
      dependent on the maximum load magnitude. DNA and protein synthesis were
      significantly enhanced in bones that were cyclically loaded at 0.5 Hz/1000
      microstrain, 0.5 Hz/2000 microstrain, or l Hz/1000 microstrain, compared to
      nonloaded controls. Anabolic responses were maximal at a peak load of 100 mN at l
      Hz/1000 microstrain. Autoradiography of the bones loaded under these conditions
      showed proliferation of cells at periosteal surfaces. Hysteresis energy per cycle
      was greatest at loads that caused the largest anabolic responses. The parameters
      of strain and load that elicit optimal effects on the neonatal bones are
      comparable to those in other systems, validating the use of the instrumentation
      for studying the mechanisms of the anabolic responses. The findings also suggest
      that hysteresis energy per cycle may be a determinant of the anabolic response of
      bones to mechanical stimulation.

PMID- 12232684
TI  - Visuomotor control within a distributed parieto-frontal network.
AB  - The aim of this functional magnetic resonance imaging study was to investigate
      differences in visuomotor control with increasing task complexity. Twelve right
      handed volunteers were asked to perform their signature under different degrees
      of visual control: internally generated movement with closed eyes, signing with
      open eyes, tracking the line of the projected signature forwards, and tracking
      the line of the projected signature backwards. There was a gradual onset and
      disappearance of activation within a distributed network. Parietal, lateral and
      medial frontal brain areas were activated during all conditions, confirming the
      involvement of a parieto-frontal system. The weight of activation shifted with
      increasing task complexity. Internally generated movements activated
      predominantly the inferior parietal lobule and the ventral premotor cortex, as
      well as the rostral cingulate area, pre-supplementary motor area (pre-SMA) and
      SMA proper. Opening the eyes reduced SMA and cingulate activation and activated
      increasingly the occipito-parietal areas with higher task complexity. Visually
      guided movements produced an activation predominantly in the superior parietal
      lobule and dorsal premotor cortex. This study bridges human activation studies
      with the results of neurophysiological studies with monkeys. It confirms a
      gradual transition of visuomotor control with increasing task complexity within a
      distributed parieto-frontal network.

PMID- 12232685
TI  - Coupling of antagonistic ankle muscles during co-contraction in humans.
AB  - In 35 healthy human subjects coupling of EMGs recorded from the tibialis anterior
      (TA) and soleus (Sol) muscles during voluntary co-contraction was analysed in the
      time and frequency domains. Two patterns were observed in different subjects or
      in the same subject on different occasions. One pattern consisted of central
      peaks in the cumulant density function of the two signals, which was often
      accompanied by coherence in the 15-35 Hz frequency band. The other pattern
      consisted of a central trough in the cumulant density function, which was mostly
      accompanied by coherence around 10 Hz. When this was the case oscillations were
      usually observed in the cumulant density function with time lags of 100 ms. Both
      patterns could be observed in the same subject, but usually not at the same time.
      Coherence around 10 Hz associated with a central trough in the cumulant density
      function was less common during weak than during strong co-contraction. The
      central peak with coherence in the 15-35 Hz frequency band in contrast tended to
      be most common during weak contraction. There was a tendency for the 10-Hz
      coherence with central trough to occur when the contractions had been maintained
      for some time. Both patterns could be observed when sensory feedback in large
      diameter afferents was blocked by ischaemia. When a central peak with coherence
      in the 15-35 Hz frequency band was observed for paired TA and Sol EMG recordings
      (10 out of 19 subjects), a coupling in the same frequency band was also observed
      between the EMG activities from the two muscles and the EEG activity recorded
      from the leg area of the motor cortex. When the central trough and the coherence
      around 10 Hz was observed for the EMG recordings (8 out of 19 subjects), no
      significant coherence was observed between EEG and EMG in 7 of the 8 subjects. In
      the last subject coherence around 10 Hz was observed. It is suggested that these
      findings signify the existence of two different central input systems to
      antagonistic ankle motoneurones: one input activates one muscle while depressing
      the antagonist and the other coactivates antagonistic motoneurones. The data
      suggest that at least the latter input depends on motor cortical activity.

PMID- 12232686
TI  - Developmental aspects of the control of manual aiming movements in aligned and
      non-aligned visual displays.
AB  - The goal of the present study was to determine for children and adults whether
      practice of a manual aiming task performed on a vertical computer display by
      moving a mouse facilitates performance of the same task but with a different
      display orientation. Children (6, 7-8, and 9-10 year olds) and adults practiced a
      video aiming task using a vertical display. Prior to and after this practice
      phase, they performed the same task but this time using a horizontal display
      simulating aiming performance in a normal environment. For all age groups, the
      results indicated that, on the amplitude component of the task, what has been
      learned with a vertical display transferred positively to performance of the same
      task with a horizontal display. No transfer, either positive or negative, was
      noted on the direction component of the task. A kinematic analysis of the
      participants' aiming movements revealed that the positive transfer noted on the
      amplitude component of the task resulted from positive transfer occurring for
      both the response planning and the motor control processes. Also differences in
      aiming performance noted between the children and the adults were caused by both
      more efficient movement planning and online control processes. Finally, the
      kinematic analysis revealed that both children and adults were able to modulate
      online their initial movement impulse, providing evidence of continuous or pseudo
      continuous movement control based on visual afferent information.

PMID- 12232687
TI  - Saccades operate in violation of Hick's law.
AB  - Hick's law states that response times (RTs) increase in proportion to the
      logarithm of the number of potential stimulus-response (S-R) alternatives. We
      hypothesized that time-consuming processes associated with response selection
      contribute significantly to this effect. We also hypothesized that the latency of
      saccades might not conform to Hick's law since visually guided saccades can be
      automatically selected using topographically organized pathways that convert
      spatially coded visual activity into spatially coded motor commands. We evaluated
      these hypotheses by examining three response modalities for their compliance with
      Hick's law: saccades directed to a visual target (prosaccades), saccades directed
      away from the target (antisaccades) and manual responses in which each digit was
      associated with a specific target location (key-press responses). Both
      antisaccades and key-press responses conformed to Hick's law but saccade
      latencies were completely unaffected by S-R uncertainty. The significance of
      these findings is considered in terms of the processes of response selection and
      premotor programming.

PMID- 12232688
TI  - The time course of attention shifts following perturbation of upright stance.
AB  - Recent work has revealed the specific time course of attention shifts associated
      with balance control in a seated model using a dual-task paradigm. This work
      highlighted an initial "automatic" and later "attention-demanding" phase of the
      evoked balance reaction. The objective of the present study was to determine if
      comparable influences would be observed for performance of a visuomotor tracking
      task when responding to perturbations of upright stability. Small-amplitude floor
      translations were applied in the forward or backward direction to evoke
      stabilizing postural reactions. Balance reactions were evoked with and without
      the concurrent performance of a visuomotor tracking task using the right hand.
      Results showed significant disruptions (pauses) in tracking that invariably
      occurred after onset of the earliest balance reaction measured in ankle muscles.
      On average, there was a delay of 345 ms between ankle-muscle activation (average
      onset 144 ms) and the pause in visuomotor tracking. The concurrent tracking led
      to modest change in later phases of the balance reaction, as measured by an
      increase in center-of-pressure excursions, but did not affect the earliest phase
      of the reaction. These results support the view that compensatory balance
      reactions, even those evoked by small perturbations, are characterized by an
      initial "automatic" phase and subsequent control that may be more dependent on
      cognitive resources.

PMID- 12232689
TI  - Timing of bimanual movements in human and non-human primates in relation to
      neuronal activity in primary motor cortex and supplementary motor area.
AB  - This study investigates the timing of bimanual movements in a combined behavioral
      and physiological approach. Human subjects and rhesus monkeys performed the same
      bimanual task. In monkeys, we simultaneously recorded neuronal activity in the
      two hemispheres of primary motor cortex (MI) or supplementary motor area (SMA),
      and related it to bimanual coordination in the temporal domain. Both for monkeys
      and humans, the reaction times of bimanual movements never significantly exceeded
      the reaction times of the slower arm in unimanual movements. Consistent with
      this, the longest delay between neural activity onset in SMA and MI and movement
      initiation was observed in unimanual movements of the slower arm and not in
      bimanual movements. Both results suggest that the programming of bimanual
      movements does not require more processing time than unimanual movements. They
      are also consistent with the view that bimanual movements are programmed in a
      single process, rather than by combining two separate unimanual movement plans.
      In both humans and monkeys, movement initiation was highly correlated between the
      arms. However, once movements began, the temporal correlation between the arms
      progressively declined. Movement decorrelation was accompanied by a net
      decorrelation of neuronal population activity in MI and SMA, suggesting a
      functional connection between neuronal interactions and the level of bimanual
      coupling and decoupling. The similarity of neuronal activities in MI and SMA in
      relationship to behavioral timing lends support to the idea that both areas are
      involved in the temporal coordination of the arms.

PMID- 12232690
TI  - Conventional anticonvulsant drugs in the guinea pig kindling model of partial
      seizures: effects of acute phenobarbital, valproate, and ethosuximide.
AB  - This study addressed the anticonvulsant effects of phenobarbital, valproate, and
      ethosuximide in the amygdala of kindled guinea pigs to further validate this
      model for the screening of anticonvulsant drugs. Behavioral toxic effects were
      assessed at 30 min following drug administration using quantitative locomotor
      tests, as well as scores on a sedation and muscle relaxation rating index. The
      anticonvulsant efficacy of the drugs were evaluated from measurements of
      afterdischarge threshold (ADT), afterdischarge duration (ADD), and behavioral
      seizure severity (SS) during early and late phases of kindling acquisition, and
      in kindled guinea pigs. ADD and SS were also measured in response to both
      threshold and suprathreshold kindling stimulation. All drugs exerted slight to
      moderate sedative effects in guinea pigs on both the behavioral tests and rating
      index. We found that phenobarbital exhibited effective anticonvulsant properties
      in guinea pigs by consistently reducing ADD and SS in response to both threshold
      and suprathreshold kindling stimulation. Valproate exhibited effective
      anticonvulsant properties at threshold stimulation and less effective properties
      at suprathreshold stimulation. Lastly, we found that ethosuximide lacked
      effective anticonvulsant action at either threshold or suprathreshold kindling
      stimulation. Our results indicate that the guinea pig kindling model correctly
      predicted the actions of phenobarbital, valproate, and ethosuximide in the
      treatment of partial seizures. Guinea pig amygdala kindling appears to serve as a
      useful and valid model for partial epilepsy.

PMID- 12232691
TI  - Finger coordination in persons with Down syndrome: atypical patterns of
      coordination and the effects of practice.
AB  - The study addresses an issue of possible relations between the apparent
      "clumsiness" of persons with Down syndrome (DS) and changes in indices of finger
      coordination. We hypothesized that persons with DS would prefer less challenging,
      safer motor strategies reflected in finger coordination patterns. Maximal single-
      and multi-finger force production (MVC) tasks and multi-finger tasks that
      required the production of a controlled time pattern (ramp) of total force were
      studied. As compared to typical persons, persons with DS showed lower peak
      forces, lower force deficit (loss of finger force in multi-finger tasks as
      compared to single-finger tasks), and higher enslaving (involuntary force
      production by fingers that are not required to produce force). They showed higher
      variance of total force computed across several trials for ramp tasks. Their
      total force variance was higher than the sum of the variances of individual
      finger forces over the ramp duration, while in control participants the relation
      was opposite during the middle and late thirds of the ramp. Persons with DS
      practiced force production tasks over 3 days, one group practicing only one of
      the tasks (the ramp task with all four fingers acting together) while the other
      group practiced MVC and ramp tasks (variable practice). Practice led to an
      increase in MVC, force deficit, and enslaving. The relation between the total
      force variance and the sum of the variances of individual finger forces became
      closer to the one observed in typical persons. The effects of practice were more
      pronounced in the variable practice group. We conclude that persons with DS have
      a deficit in control of both single fingers and multi-finger groups. They use a
      less challenging, suboptimal strategy of multi-finger coordination which does not
      take advantage of the possibility of error compensation among the fingers.
      Practice is an effective way of improving finger coordination in DS, particularly
      when using variable tasks.

PMID- 12232692
TI  - Peripheral nerve regeneration through alginate gel: analysis of early outgrowth
      and late increase in diameter of regenerating axons.
AB  - Our previous study revealed that alginate gel cross-linked with covalent bonds
      promoted peripheral nerve regeneration in the cat and rat. The present study
      analyzed nerve regeneration through alginate gel in the early stages within 2
      weeks and the late stages up to 21 months after implantation. Four days after
      surgery, regenerating axons grew without Schwann cell investment through the
      partially degraded alginate gel, being in direct contact with the alginate
      without a basal lamina covering. Numerous mast cells infiltrated into the
      alginate. One to 2 weeks after surgery, regenerating axons were surrounded by
      common Schwann cells to form small bundles, with some axons at the periphery
      being partly in direct contact with alginate. At the distal stump, numerous
      Schwann cells had migrated into the alginate 8-14 days after surgery. They had no
      basal laminae. The diameter of regenerated myelinated fibers was small
      (approximately 1 micro m) at 8 weeks, but increased in diameter, having a
      distribution pattern similar to that of normal nerve 21 months after surgery.
      Much better nerve regeneration was found in alginate gel-, than collagen sponge-,
      and fibrin glue-implanted distal stump 12 months after surgery. These results
      indicate that alginate gel has good biocompatibility for regenerating axon
      outgrowth and Schwann cell migration, and that regenerated fibers can have a
      diameter as thick as that of normal fibers in the long term. Alginate gel is a
      promising material for use as an implant for peripheral nerve regeneration.

PMID- 12232693
TI  - Motor sequence learning with the nondominant left hand. A PET functional imaging
      study.
AB  - Whereas the human right hemisphere is active during execution of contralateral
      hand movements, the left hemisphere is engaged for both contra- and ipsilateral
      movements, at least for right-handed subjects. Whether this asymmetry is also
      found during motor learning remains unknown. Implicit sequence learning by the
      nondominant left hand was examined with the serial reaction time (SRT) task
      during functional brain imaging. As learning progressed, increases in brain
      activity were observed in left lateral premotor cortex (PMC) and bilaterally in
      supplementary motor areas (SMA), with the increase significantly greater in the
      left hemisphere. The left SMA site was similar to one previously identified with
      right-hand learning, suggesting that this region is critical for representing a
      sequence independent of effector. Learning with the left hand also recruited a
      widespread set of temporal and frontal regions, suggesting that motor skill
      learning with the nondominant hand develops within both cognitive and motor
      related functional networks. After skill acquisition, subjects performed the SRT
      task with their right hands, and sequence transfer was tested with the original
      and a mirror-ordered sequence. With the original sequence, the stimulus sequence
      and series of response locations remained unchanged, but the finger movements
      were different. With the mirror-ordered sequence, the response sequence involved
      finger movements homologous to those used during training. Performance of the
      original and mirror sequence by the right hand was significantly better than with
      random stimuli. Mirror transformation of the sequence by the right hand was
      associated with a marked increase in regional activity in the left motor cortex,
      consistent with a role for sequential transformation at this level of the motor
      output pathway.

PMID- 12232694
TI  - Interaction of visual and idiothetic information in a path completion task.
AB  - To assess the contribution of visual and vestibular information on human
      navigation, five blindfolded subjects were passively displaced along two sides of
      a triangular path using a mobile robot. Subjects were required to complete the
      triangle by driving the robot to the starting point either blindfolded or in full
      vision in a 7x6-m and a 38x38-m room. Room dimensions exerted a significant
      effect on performances: in the smaller environment blindfolded responses were
      always too short whereas subjects correctly reached the starting point when
      visual feedback was allowed. On the contrary, in the larger room subjects
      correctly responded while blindfolded but drove significantly farther than
      requested in full vision. Our data show that vestibular navigation is highly
      sensitive to both stored (knowledge of environment) and current visual
      information.

PMID- 12232695
TI  - Semantics affect the planning but not control of grasping.
AB  - The semantic meaning of a word label printed on an object can have significant
      effects on the kinematics of reaching and grasping movements directed towards
      that object. Here, we examined how the semantics of word labels might
      differentially affect the planning and control stages of grasping. Subjects were
      presented with objects on which were printed either the word "LARGE" or "SMALL."
      When the grip aperture in the two conditions was compared, an effect of the words
      was found early in the reach, but this effect declined continuously as the hand
      approached the target. This continuously decreasing effect is consistent with a
      planning/control model of action, in which cognitive and perceptual variables
      affect how actions are planned but not how they are monitored and controlled on
      line. The functional and neurological bases of semantic effects on planning and
      control are discussed.

PMID- 12232696
TI  - Context-specific adaptation of the gain of the oculomotor response to lateral
      translation using roll and pitch head tilts as contexts.
AB  - Previous studies established that vestibular and oculomotor behaviors can have
      two adapted states (e.g., gain) simultaneously, and that a context cue (e.g.,
      vertical eye position) can switch between the two states. The present study
      examined this phenomenon of context-specific adaptation for the oculomotor
      response to interaural translation (which we term "linear vestibulo-ocular
      reflex" or LVOR even though it may have extravestibular components). Subjects sat
      upright on a linear sled and were translated at 0.7 Hz and 0.3 gpeak acceleration
      while a visual-vestibular mismatch paradigm was used to adaptively increase (x2)
      or decrease (x0) the gain of the LVOR. In each experimental session, gain
      increase was asked for in one context, and gain decrease in another context.
      Testing in darkness with steps and sines before and after adaptation, in each
      context, assessed the extent to which the context itself could recall the gain
      state that was imposed in that context during adaptation. Two different contexts
      were used: head pitch (26 degrees forward and backward) and head roll (26 degrees
      or 45 degrees, right and left). Head roll tilt worked well as a context cue: with
      the head rolled to the right the LVOR could be made to have a higher gain than
      with the head rolled to the left. Head pitch tilt was less effective as a context
      cue. This suggests that the more closely related a context cue is to the response
      being adapted, the more effective it is.

PMID- 12232697
TI  - Movement reorganization to compensate for fatigue during sawing.
AB  - Peripheral (muscle) aspects of fatigue are well documented. However, little is
      known about the central aspects of fatigue that could influence, in particular,
      multijoint coordination. To investigate the central aspects of fatigue, we
      compared the multijoint kinematics of non-fatigued and fatigued individuals while
      sawing. Muscle fatigue was associated with decreases in sawing force and movement
      amplitude at the elbow whereas the basic characteristics of the saw trajectory,
      including the movement direction, extent and duration, remained invariant. This
      invariance was maintained by increasing the movement amplitude at the wrist,
      shoulder and trunk. The system thus takes advantage of the redundancy of the
      motor apparatus to maintain the endpoint trajectory despite fatigue.

PMID- 12232698
TI  - Plateau potentials in hindlimb motoneurones of female cats under anaesthesia.
AB  - Central respiratory drive potentials (CRDPs) were observed in intracellular
      recordings from hindlimb motoneurones of anaesthetized, paralysed,
      ovariohysterectomized female cats, artificially ventilated so as to have a strong
      respiratory drive under hyperoxic hypercapnea. The animals comprised two groups:
      three animals treated for 7 days with oestradiol benzoate (oestrous), and three
      untreated (non-oestrous). Several features of the CRDPs suggested the involvement
      of voltage-sensitive channels, including variability in the CRDP amplitude and
      potentiation of the CRDP by depolarizing currents. Clear plateau potentials,
      related to or triggered by depolarizing phases of the CRDPs, occurred in six
      motoneurones, three in response to depolarizing currents, three spontaneously.
      This is the first report of plateau potentials in mammalian motoneurones under
      anaesthesia. The mechanisms accessed here by the respiratory inputs are deduced
      to be particularly potent, perhaps because of a distal dendritic location.
      Plateau-like effects were more common in the oestrous animals, which suggests a
      specific role for the plateau potentials in the production of the stereotyped
      movements of female receptive behaviour.

PMID- 12232699
TI  - Diaphragmatic silent period to transcranial magnetic cortical stimulation for
      assessing cortical motor control of the diaphragm.
AB  - This study was designed to determine whether a silent period could be elicited in
      the diaphragm electromyographic (EMG) activity by transcranial magnetic
      stimulation (TMS) of the motor cortex and, if so, to assess the influence of
      reflex or voluntary control of breathing on diaphragmatic cortical silent period
      (cSP). Diaphragmatic EMG activity was recorded in six healthy volunteers after
      motor cortex TMS triggered by the inspiratory flow peak and applied during forced
      inspiration (FI), voluntary hyperventilation (vHV) and reflex hyperventilation
      (rHV) to a CO(2) stimulus. Electrophysiological and respiratory parameters were
      studied, including diaphragmatic cSP duration and transdiaphragmatic pressure
      swing (DeltaPdi). A diaphragmatic cSP was found and correlated with DeltaPdi
      values. DeltaPdi and cSP duration were similar in the vHV and rHV conditions but
      were significantly increased during FI. This study established for the first time
      the existence of a diaphragmatic cSP to motor cortex TMS. The diaphragmatic cSP
      duration depended on the magnitude of the respiratory effort, as assessed by
      DeltaPdi, but not on the mechanism (volitional or reflex) of diaphragm
      activation.

PMID- 12232700
TI  - [Development and functional structure of the epiphyseal plate].
AB  - The longitudinal growth of long bones occurs in the epiphyseal plates at their
      ends. After a center of ossification has developed in the epiphysis, a
      cartilaginous plate, characterized by a typical zonal arrangement is formed. The
      cartilaginous plate proliferates using cells from a reservoir at the epiphyseal
      (i.e. articular) side of the plate. The cells are orientated to longitudinal rows
      and become thickened towards the metaphysis. The extracellular matrix between the
      hypertrophic chondrocytes becomes calcified and is subsequently replaced in an
      ossification process by lamellar bone. Cell proliferation in the epiphyseal plate
      is regulated by a number of different factors (e.g. IGF-I and BMP-7). The
      extracellular matrix is rich in glycosaminoglycans, proteoglycans and type II
      collagen, whereas especially at the edges type I and type VI collagen can be
      observed, too. The three dimensional orientation of the epiphyseal plate is
      determined by local mechanical influences. The adjacent bony endplates exhibit a
      higher central mineralization pattern with lower density values at their edges.
      The region of failure predominantly concerns the proximal zone of the
      longitudinal rows. The mechanical properties of the epiphyseal plate are
      influenced by endocrine as well as by metabolic factors. Any case of an
      epiphysiolysis is caused by a misproportion between acting shear forces and
      cartilaginous strength.

PMID- 12232701
TI  - [Radiology and measurement in adolescent slipped capital femoral epiphysis].
AB  - Two X-rays taken in two planes perpendicular to each other secure the early
      diagnosis of adolescent slipped capital femoral epiphysis (SCFE). In imminent
      SCFE, two radiographic features are considered the most important signs: the
      broadening and the irregular demarcation of the upper femoral epiphyseal plate.
      In the beginning of SCFE, the process of dislocation is much better visible in
      the second radiographic plane (the lateral tangent of the femoral neck builds a
      smaller secant of the lateral femoral head). In chronic SCFE, the aforementioned
      radiographic signs including the epiphyseal dislocation are more marked. An
      additional feature can be various deformities of the femoral neck and duplicate
      contours of the medial demarcation of the femoral neck. In acute SCFE, there is a
      complete disruption of continuity between the metaphysis and epiphysis. Beside
      the marked gap in the epiphyseal plate, there is a severe dislocation between the
      femoral neck and the epiphysis. There are also partly patchy, partly cystic
      changes in the metaphyseal part of the femoral neck. The so-called acute on
      chronic slip, a sudden slip of the upper epiphysis after prolonged chronic
      slipping, is considered a specific case of SCFE. The long-term result of treated
      as well as untreated SCFE can be the gradual increase of coxarthrosis, which is
      typically more marked in the medial direction of the joint. The direction and the
      degree of the epiphyseal slip play an important role in the development of
      "epiphyseal" coxarthrosis. The planning of corrective operations as well as the
      quantitative evaluation of the prearthrotic deformity require the conversion of
      angles of dislocation that are projected on X-rays into anatomically correct
      angles. This conversion is done with tables that were created with the aid of
      computers and requires that the positioning of the femur for taking the X-rays is
      always done under standardized conditions.Mostly, in minor dislocations in the
      usual direction (medially and dorsally), the difference between the projected and
      the real angles is relatively small. Therefore, in these cases of SCFE it might
      not be necessary for practical and operative needs to convert these angles into
      real angles. However, this simplification is only then acceptable if the
      prescribed positioning of the femur for taking the X-rays is strictly adhered to
      so that additional errors of projection are excluded.

PMID- 12232702
TI  - [Value of ultrasound, CT, and MRI in the diagnosis of slipped capital femoral
      epiphysis (SCFE)].
AB  - Traditionally, radiographic assessment of the hip with anteroposterior and
      lateral views is the gold standard of diagnosis in SCFE. This paper evaluates the
      possible contributions of other methods of modern imaging to the early diagnosis
      and treatment. There is scientific evidence that ultrasound can diagnose the
      disease earlier than conventional radiography and also has the possibility to
      differentiate the classification between stable and unstable. MRI depicts marrow
      changes earlier than any other imaging method available and has a role in cases
      where the diagnosis is difficult to make as well as in assessing the risk of
      chondrolysis and avascular necrosis. To show the anatomic deformity,
      anteroposterior and lateral radiographs remain the mainstay of preoperative
      planning.

PMID- 12232703
TI  - [Treatment of acute slips and clinical results in slipped capital femoral
      epiphysis].
AB  - In looking at the pathoanatomy of slipped capital epiphysis, it is important to
      appreciate that the articular cartilage ruptures at the level of the physis as
      the articular cartilage also covers part of the femoral neck metaphysis. As a
      consequence, smoothness is lost and already with mild slips the irregularities
      may injure the acetabular cartilage structures and may cause tears of the labrum.
      Principally therefore an open revision and restoration of the anatomy as
      perfectly as possible is needed. The technique for open reduction was developed
      by Dunn in 1964 and then refined by Ganz in 1997 applying new anatomical vascular
      studies. However, the long-term data on the "conservative" approach of only using
      transfixation to avoid further slipping show relatively good results and long
      term studies of a more aggressive open approach will be needed to show evidence
      of further improvement. For the more severe cases, restoration of the correct
      anatomy by open reduction or improved axial relationships by more distant
      osteotomies have already been proven to give better results. Besides the extent
      of the slip, it is important to consider whether the slip is acute or chronic or
      acute and chronic. So far there are no data showing that the surgical treatment
      of slipped capital femoral epiphysis must be made on an emergency basis. However,
      prevention of further slips, e.g., by supine transport, is to be considered an
      emergency.

PMID- 12232704
TI  - [Management and treatment results for acute slipped capital femoral epiphysis].
AB  - The priorities in treating an acute slip are to avoid avascular necrosis and
      chondrolysis. Other aims in the unstable situation are to prevent further slip
      and to correct deformity. We reviewed the management of 16 unstable slips after
      nearly 9 years. Fifteen patients underwent reduction and stabilization with K
      wires within 24 h of the onset of severe symptoms. Only one patient in this group
      developed avascular necrosis (6.6%) and in no case was chondrolysis seen. No
      correlation was noted between slip magnitude and the development of avascular
      necrosis. Therefore, we recommend in cases of unstable slips early reduction and
      stabilization to reduce the risk of avascular necrosis and chondrolysis.

PMID- 12232705
TI  - [Dyamic screw fixation for slipped capital femoral epiphysis. Treatment results].
AB  - Slipped capital femoral epiphysis always requires surgical treatment. The
      operative technique depends on the degree of dislocation and the type of the
      slip. The goal of treatment is to achieve physeal stability until the epiphyseal
      plate closes without harming the further femoral growth. In situ fixation is
      generally recommended for slipped capital femoral epiphyses of a mild degree. For
      this purpose the technique of dynamic screw fixation (DSF) is applicable using a
      long cannulated screw with a short thread.DSF is easy to handle, provides
      sufficient long-term fixation of the epiphysis, does not promote premature
      closure of the epiphysis, and engenders few complications. Therefore, this
      technique is also applicable for the prophylactic treatment of the contralateral
      unaffected hip, which we always perform. Moreover, DSF can be used following
      gentle reduction of acute epiphysiolysis, if the amount of eventual residual
      dislocation does not exceed 30 degrees. We report our results with dynamic screw
      fixation of 29 slipped capital femoral epiphyses of a mild degree, and the
      prophylactic dynamic screw fixation of 34 unaffected hips. The fixation technique
      achieved a reliable stabilization with no visible growth disturbance of the
      femoral neck in all cases.

PMID- 12232706
TI  - [Results of treating slipped capital femoral epiphysis by pinning in situ].
AB  - The primary aim in treatment of chronic SCFE consists of immediate stabilization
      of the epiphysis to prevent further slipping. For mild degrees of slipping (<30
      degrees ), pinning in situ is the treatment of choice. With slips between 30 and
      50 degrees, the decision should be based on individual factors (age, functional
      limitation of the hip joint) whether pinning in situ is sufficient or whether an
      additional intertrochanteric osteotomy according to Imhauser should be
      performed.The choice of implant should ensure a safe and stable connection
      between the epiphysis and the femoral neck without resulting in a substantial
      impairment of growth of the femoral neck due to premature closure of the growth
      plate. Since 1982 we have used K wires for in situ pinning of the affected hip as
      well as for prophylactic pinning of the nonaffected hip with a low complication
      rate. In a clinical and radiological study, 65 patients with a chronic slip of
      less than 50 degrees could be assessed after in situ pinning. Almost 75% were
      pain-free after a follow-up interval of 9.8 years, and 92% achieved a good or
      very good result according to the criteria of the Iowa hip score, the mean score
      being 95.1 points. According to the radiological score of Schulitz, five patients
      (7.7%) demonstrated a grade I osteoarthritis. One patient showed a partial
      necrosis of the femoral head; chondrolysis was not observed.

PMID- 12232707
TI  - [Slipped capital femoral epiphysis and the "healthy" opposite hip].
AB  - The gold standard in the therapy of SCFE is the bilateral procedure in Central
      Europe. Several statistics demonstrate more than 30% of bilateral slippage as an
      average. Complications such as accidental pin perforation have become rare since
      the introduction of large cannulated screws. The advantage of screws as an
      implant is the easier removal of the device after termination of growth.
      Exceptionally, only the involved site may be operated on when cessation of growth
      is to be expected immediately. Because the disease takes place in the growing
      area of the femur, leg length differences up to 2 cm are not unusual and cannot
      always be avoided.

PMID- 12232708
TI  - [Early damage to the acetabular cartilage in slipped capital femoral epiphysis.
      Therapeutic consequences].
AB  - Epiphyseolysis capitis femoris represents the most common disorder of the
      adolescent hip, which is followed by a significant rate of early osteoarthrosis.
      Based on intraoperative findings during the surgical management of 23 hips with
      epiphyseolysis, early acetabular cartilage abrasion by a cam effect and
      acetabular rim impingement elicited by the prominent femoral metaphysis have been
      identified. Both phenomena cause direct damage to the hip joint, especially
      during flexion and flexion/internal rotation of the hip. As evidenced during
      surgery, the prominent and sometimes sharp-edged anterior neck metaphysis
      leveling or exceeding the femoral head showed marks of contusion and the labrum
      revealed erosions, scars, or tears. Moreover, adjacent acetabular cartilage
      damage was present ranging from superficial abrasions to a full thickness
      cartilage loss propagating into the weight-bearing area. In all patients the
      femoral head cartilage was intact; no avascular necrosis was present. These
      findings suggest that osteoarthrosis is triggered by direct mechanical damage in
      the epiphysiolysis hip already during the process of slipping and that
      chondrolysis appears to represent just the most severe form of this cartilage
      damage. Consequently, we propose that treatment should not only address the
      avoidance of a further slippage but also the prevention of impingement and cam
      leading to early acetabular cartilage damage.

PMID- 12232709
TI  - [Indication for and results of intertrochanteric osteotomy in slipped capital
      femoral epiphysis].
AB  - The progression of degenerative changes of the hip after slipped capital femoral
      epiphysis (SCFE) largely correlates with the patient's age at the time the
      deformity occurs and with the degree of the epiphyseal gliding. From the
      pathogenetic point of view, the altered biomechanical conditions of the hip joint
      with deformation of the proximal femur may result in an impingement of the
      femoral neck metaphysis against the anterior acetabular rim. Observations of the
      "natural course" or after "in situ fixation" of the epiphysis show the
      development of secondary hip arthritis at an average of 20 years after SCFE,
      specifically in slips with more than 30 degrees of epiphyseal gliding. The
      intertrochanteric osteotomy as introduced by G. Imhauser aims at restoring joint
      congruity to reduce the prearthrotic deformity and thus to decrease the incidence
      of later hip arthritis. The reorientation of the predominantly posteriorly
      slipped femoral epiphysis is achieved by an intertrochanteric flexion osteotomy,
      which reduces the potential for femoroacetabular impingement. On the basis of a
      long-term evaluation, the indication for and results of an intertrochanteric
      osteotomy for chronic unilateral SCFE were presented. Of the 51 patients operated
      on between 1962 and 1972 and examined clinically and radiographically at an
      average follow-up time of 24 years (20-29 years) after osteotomy, 55% showed a
      hip free of degenerative changes, 28% had developed moderate degenerative
      changes, and 17% had advanced arthritis. Aside from a few technical errors, the
      correction at the intertrochanteric level for moderate slips proved to be a safe
      procedure regarding risk for femoral head necrosis. The long-term development
      after SCFE is most important for patients with SCFE. More than half of the
      patients have hip joints free of degenerative changes more than 20 years after
      intertrochanteric osteotomy according to G. Imhauser, which compares favorably to
      the "natural course" or to "in situ fixation" and which supports the indication
      for this corrective procedure in SCFE.

PMID- 12232710
TI  - [Significance and results of subcapital osteotomy in severe slipped capital
      femoral epiphysis].
AB  - Today treatment with in situ fixation for mild slips in chronic SCFE is
      undisputed. However, it is far more difficult to give a definite recommendation
      in cases where a severe dorsal slip of >70 degrees has already occurred. With
      this position of the femoral head, a severe functional deficit combined with an
      early onset of osteoarthritis has to be expected. With these severe slips we
      prefer the subcapital osteotomy, a technique which results in an almost normal
      anatomical alignment of femoral head and acetabulum. In the literature, this
      procedure is subject to controversy because of the relatively high incidence of
      avascular necrosis and chondrolysis. In our own small collective of five
      patients, we did not observe these complications in the postoperative follow-up
      and the clinical results were excellent. After 8.5 years the Iowa score was a
      mean of 91.8 points. Only one patient showed radiological signs of grade I
      osteoarthritis; the follow-up interval was, however, relatively short.

PMID- 12232711
TI  - [Biomechanics of the tibiofemoral joint and knee braces].
AB  - We investigated whether the kinematics of modern knee braces reflect the natural
      movement of the knee, especially with regard to the roll-glide ratio. Seven
      commercially available modern knee braces were analyzed in a new measuring unit
      with a 6-D positional registration system, which had been developed for this
      study. The results were compared to the theoretically postulated joint movements.
      All knee braces produced a roll-glide ratio different from the natural movement
      of the knee. Only the Townsend brace protected the anterior cruciate ligament at
      the beginning of the movement.Biomechanically, none of the knee braces tested
      provided efficient protection for the knee movement. We propose a new functional
      external joint, which allows restoration of the natural roll-glide mechanism of
      the articulating surfaces.

PMID- 12232712
TI  - [F-18 FDG positron emission tomography in diagnosis and follow-up of patients
      with musculoskeletal tumors].
AB  - The purpose of this study was to assess the value of F-18 FDG whole body positron
      emission tomography in the primary and follow-up diagnosis of musculoskeletal
      tumors. Between May 1994 and January 2000, 79 patients [36 females, 43 males;
      mean age: 44 years (9-78)] suffering from different musculoskeletal tumors were
      additionally examined with PET. In total, 100 whole body PET examinations (48 for
      primary staging, 52 for follow-up) were performed using a PET scanner [ECAT EXACT
      47 (921)] with an axial field of view of 16.2 cm. The tracer was 370 MBq F-18
      FDG. The results were compared to those achieved with conventional diagnostic
      tools such as CT, MRT, bone scan, and histology. In the primary staging, PET
      exhibited a sensitivity of 100% and a specificity of 50% (two false-positive
      results). In examinations for follow-up purposes, we found a sensitivity of 88.9%
      and a specificity of 92.0%. In the diagnosis of skeletal and extraskeletal
      metastases (100 PET inspections), the sensitivity was 87.5% and the specificity
      89.7%. Besides this, PET was compared with standard diagnostic tools used in the
      follow-up procedures of those patients who had received chemo- and/or
      radiotherapy. In addition, the procedure was used to search for the unknown
      primary tumors in cases of secondary metastases in the skeleton and compared as
      well.PET with F-18 FDG as tracer has become an important additional method in the
      diagnosis of musculoskeletal tumors. It can be used for primary staging, search
      for metastases, and post therapeutic control. Negative results were seen when PET
      was used to search for metastases when the tumor was smaller than 5 mm, in cases
      of inflammatory diseases, and the differentiation of low-grade malignant tumors
      from benign lesions.

PMID- 12232713
TI  - [Spontaneous epiphyseal injury as a complication of a simple bone cyst of the
      femoral neck? Case report and review of the literature].
AB  - A case of a spontaneous epiphyseal injury of the femoral neck in an 8-year-old
      boy is reported. The same boy had been seen 8 months before for a pathological
      fracture caused by a simple bone cyst of the femoral neck on the same side. At
      the second visit the boy showed spontaneous severe pain of the hip, and
      radiography was performed under the presumed diagnosis of a slipped capital
      femoral epiphysis. However, it demonstrated a separation through the growth plate
      cranially and a fracture through the metaphysis inferiorly, leading to the
      differential diagnosis of a Salter-Harris type II fracture despite a nontraumatic
      patient history.A review of the literature failed to reveal a similar report of
      simultaneous occurrence of a simple bone cyst and epiphyseal injury of the femur.
      However, slipping of the proximal humeral epiphysis in connection with a simple
      bone cyst has been described by some authors. We propose a pathophysiological
      model for the simultaneous occurrence of epiphyseal injury and a simple bone
      cyst. Physeal involvement by a simple bone cyst and varus deformity of the
      femoral neck could cause weakening of the growth plate and predispose for
      epiphyseal injury. Based on these findings, we suggest that a simple bone cyst of
      the proximal femoral metaphysis can develop into a severe condition. Children
      presenting with this clinical picture should be treated vigorously and monitored
      for the development of complications leading to epiphyseal injury.

PMID- 12232714
TI  - [Surgical approaches for primary endoprosthesis of the knee joint].

PMID- 12232715
TI  - 2,4,6-trichlorophenol degradation by river sediment exposed to bleached kraft
      mill discharge.

PMID- 12232716
TI  - Effect of extrusion processing on fumonisin B(1) and hydrolyzed fumonisin B(1) in
      contaminated alkali-cooked corn.

PMID- 12232717
TI  - Persistence of methamidophos, diazinon, and malathion in tomatoes.

PMID- 12232718
TI  - PAH levels in bivalve mollusks from the Mexican subtropical Pacific.

PMID- 12232719
TI  - Direct determination of 1-hydroxypyrene in fish from coastal water by synchronous
      fluorimetry.

PMID- 12232721
TI  - Concentration and discrimination of selected trace metals by freshwater mollusks.

PMID- 12232720
TI  - Isotopic characterization of various brands of corroding grade refined lead
      metal.

PMID- 12232722
TI  - Mercury speciation and relationship between mercury and selenium in liver of
      Galeus melastomus from the Mediterranean sea.

PMID- 12232723
TI  - Heavy metal concentrations in fish from a pristine rainforest valley in Peru: a
      baseline study before the start of oil-drilling activities.

PMID- 12232724
TI  - Metal residues in process water used in seafood processing industries.

PMID- 12232725
TI  - Arsenic in groundwater of the Bengal delta plain aquifers in Bangladesh.

PMID- 12232726
TI  - Copper tolerance and accumulation potential of Chlamydomonas reinhardtii.

PMID- 12232727
TI  - Response of Chlamydomonas reinhardtii to herbicides: negative relationship
      between toxicity and water solubility across several herbicide families.

PMID- 12232728
TI  - Comparative contaminant toxicity: are amphibian larvae more sensitive than fish?

PMID- 12232729
TI  - Metabolic enzymes as biochemical markers of effect following exposure of fish to
      sodium pentachlorophenate (Na-PCP).

PMID- 12232730
TI  - Differentiating metal from ammonia toxicity in toxicity identification
      evaluations.

PMID- 12232731
TI  - Cadmium-fenitrothion interaction in the spider Pardosa lugubris and the fruit fly
      Drosophila melanogaster.

PMID- 12232732
TI  - Effects of dietary exposure to environmentally relevant concentrations of
      weathered Prudhoe Bay crude oil in ranch-raised mink ( Mustela vison).

PMID- 12232733
TI  - Sensitivity of the rooted macrophyte Myriophyllum aquaticum (Vell.) verdcourt to
      seventeen pesticides determined on the basis of EC(50).

PMID- 12232734
TI  - Endosulfan affects pheromonal detection and glands in the male red-spotted newt,
      Notophthalmus viridescens.

PMID- 12232735
TI  - [Partial Fusion of the wrist - an alternative procedure to the total wrist
      arthrodesis].
AB  - Despite the important observations that have been made concerning biomechanics
      and function of the wrist joint in recent years, the surgeon is still confronted
      with a huge number of delayed posttraumatic disorders of this joint. In the past,
      total wrist fusion was the leading salvage procedure, whereas today several
      salvage procedures are available to solve these problems. Partial wrist fusions
      are supposed to stabilize the carpus, immobilize destroyed articulating surfaces
      while allowing motion in the unharmed parts of the wrist. Acknowledging
      pathobiomechanical laws, they have been used for a growing number of indications
      with a large benefit. The patients profit of better functional results than can
      be observed in patients with total arthrodesis of the wrist. Furthermore, partial
      wrist fusion provides a more stable situation and the absence of pain for a
      longer period of time. However, further studies evaluating the clinical outcome
      of these salvage procedures are necessary and to be expected in the near future.

PMID- 12232736
TI  - [Pathomorphology, diagnosis and treatment of "hangman's fractures"].
AB  - In a retrospective study diagnostic procedures and outcome of treatment were
      evaluated in 33 patients with traumatic spondylolisthesis of the axis (Hangman's
      fracture) who were treated in our department between 1986 and 1999. There were 18
      men and 15 women with an average age of 41 (17-88) years. The cause of the injury
      was in 23 cases an accident as a driver of a car, in 2 cases an accident with a
      bike, 2 patients had an accident as a pedestrian. 5 patients fell on their head
      and 1 patient was hit by a beam. In 15 cases there were relevant accompanying
      injuries. To assess the stability of the injury, a subtle radiological
      examination was performed including functional X-rays. After introduction of the
      MRI and increasing experience with the method as a standard procedure in clinical
      practice it was used instead of functional X-rays to get a direct image of the
      involvement of the discoligamental structures.17 patients with stable lesions
      were treated conservatively, 15 with a Minerva-cast, 2 with a halo-jacket. One
      polytraumatized patient had temporary immobilization with a stiff-neck. 16
      patients with discoligamental instability C2/3 were treated operatively by
      Robinson-spondylodesis with additional anterior plating. In one case an
      additional posterior fusion was necessary. After 6-8 weeks all of the
      conservative treated patients achieved solid bony consolidation. The patients
      operated on did so as well within 6 to 8 weeks. Two polytraumatized patients
      died. 18 of the 31 surviving patients were free of pain. 12 patients complained
      of pain or tension of the cervical muscles during physical stress. 1 patient
      suffered of paresthesia of the ulnar left hand. Average duration of hospital stay
      was 12,9 days (1-47). All working people returned to their job. Differences in
      the outcome of the conservative and the operative treatment group could not be
      seen. We derive from these results that Hangman's fractures, mostly caused by a
      hyperextension trauma, achieve solid bony fusion by conservative treatment in
      most of the cases. The Minerva-cast has proved its capability. In cases of
      instable luxation fractures including tearment of the anterior longitudinal
      ligament and affection of the intervertebral disc C2/3 we suggest operative
      stabilization. We prefer the modified Robinson-spondylodesis with additional
      anterior plating which proved its value as a method achieving solid bony fusion
      combined with low rate of complications.

PMID- 12232737
TI  - [Clinical evaluation of the distal femoral nail].
AB  - METHOD: The clinical results after DFN-osteosynthesis of n=56 AO-classification
      33A-fractures (32%), 33C-fractures (43%), 32X-fractures (21%) and pseudarthrosis
      treatment (4%) are presented. RESULTS: Follow up was available for 54 fractures
      (96%) after a mean of 1.2 years (range 0.2-2.8 years). 95% of patients showed
      full-weight-bearing with a knee flexion of 120 (60-140) degrees. Extension
      deficit >10 degrees was observed in 5.4%. All fractures were consolidated. One
      soft-tissue infection, one partial loss of reduction and one implant failure were
      observed. A significant axial malalignment was found radiologically in 17%, a
      loosened spiralblade or locking screw in 7.4%. In 91% of cases the result was
      judged as good to excellent by patients and surgeons. CONCLUSION: The mechanical
      stability of the implant allows a save osteosynthesis of unstable supracondylar
      and complete articular femoral fractures without additional bone grafting.
      Mechanical stability and minimal invasive operative technique permit a safe bone
      healing without major complications.

PMID- 12232738
TI  - [Influence of unfractionated and low-molecular-weight heparin on bone healing: an
      animal model].
AB  - The inhibition of bone metabolism and development of osteoporosis under treatment
      with unfractionated heparins (UFH) have been discussed, whereas the
      pathomechanism and the question of whether low-molecular-weight heparins (LMWH)
      have an influence on bone healing as well remain unclear. In a blinded trial,
      three groups of ten rabbits received subcutaneous injections of an unfractionated
      heparin (sodium heparin), a low-molecular-weight heparin (certoparin), or normal
      saline over a period of 6 weeks after a standardized bone defect had been applied
      to both femur condyles. Healing of the defects was investigated in a depth of 1
      and 2 mm and the remaining volume of the bone defects was measured. After therapy
      with UFH, the volume of the defects remained significantly larger in a depth of 1
      mm (UFH/control: p<0.001; UFH/LMWH: p<0.005) and in the total depth (UFH/control:
      p<0.005; UFH/LMWH: p<0.025). After therapy with LMWH, there was no inhibition of
      defect healing (p>0.05). This study shows that the influence of heparins on
      fracture healing can be reduced significantly by using LMWH instead of UFH.

PMID- 12232739
TI  - ["Biorigid" interlocking after unreamed intramedullary nailing of tibial shaft
      fractures].
AB  - Between April 1996 and December 1999, 76 tibial shaft fractures were treated at
      the Department of Trauma Surgery of the Justus-Liebig-University in Giessen,
      Germany and the Department of Orthopedic Surgery of the University of Louisville,
      USA with a newly developed, unreamed, solid, small diameter tibial nail
      interlocked "biorigidly" with screws in grooves of the nail. 69 Patients were
      reviewed with a minimal follow-up period of 16 months. In 65 patients, the
      fractures united without exchange nailing, although four of these fractures
      showed a delay of healing. In further four cases, non-union occurred, one of
      which was associated with the only break of a nail located at a distal
      interlocking groove of the nail. In one patient, a late medullary infection so
      far has not recurred following treatment. In 358 implanted interlocking screws,
      no implant failure was observed. First clinical experience suggests that,
      especially due to the low rate of material fatigue, the biorigid nail is an
      alternative to other implants for unreamed intramedullary nailing of the tibia.

PMID- 12232740
TI  - [Good long term results with a cemented straight femoral shaft prosthesis made of
      titanium].
AB  - A higher-than-average rate of aseptic loosening has been postulated to be
      associated with the combination of a titanium stem and bone cement. In this
      prospective follow-up study we therefore investigated our first consecutive
      series of 250 implantations of a cemented femoral shaft prosthesis made of
      titanium alloy (BiCONTACT((R)), Aesculap, Tuttlingen, Germany). Average time of
      follow-up evaluation was 9.7 years (range 8.7-10.3 years). At follow-up, mean
      patient age was 81 years; 89 patients with 93 hips have deceased and two could
      not be located. Follow-up rate was 98.7% for the patients still alive at time of
      follow-up evaluation. Five patients have been revised, two for infection and one
      for aseptic loosening of a varus-malaligned stem; two radiologically well-fixed
      stems had been revised during acetabular revision. Survival estimate showed a
      calculated cumulative survival rate of 97.5% after 11 years [confidence limits:
      99.0% (upper) and 94.1% (lower)]. The average Harris hip score at time of follow
      up was 82.25 points.Radiologically, signs of loosening could be detected in 3
      stems: in one case varus malalignement deteriorated with time and in 2 cases
      osteolyses developed together with significant polyethylene wear. All 3 patients
      experienced only mild pain and revision had not been indicated so far. In
      conclusion, the long-term follow-up results with this cemented titanium femoral
      component are encouraging and are comparable to other successful cemented femoral
      components in primary total hip arthroplasty. No increased risk for aseptical
      loosening was associated to the combination of titanium and cement in this
      specific stem. Design parameters seem to play an important role in the
      development of aseptic loosening in cemented titanium stems.

PMID- 12232741
TI  - [Simultaneous traumatic rupture of the patellar and contralateral quadriceps
      tendon].
AB  - We report a very rare case of a simultaneous rupture of the right patellar and
      left quadriceps tendon in an otherwise healthy 37-year-old patient, who jumped
      off a kickboard. Suture of both tendons was performed on the day of trauma. We
      describe our postoperative treatment and report the follow-up examination one
      year after the trauma. Beside functional questionnaire, Lysholm score and
      physical examination and x-ray, quadriceps isokinetic testing was performed.

PMID- 12232742
TI  - [The hypothenar hammer syndrome].
AB  - The hypothenar hammer syndrome (HHS) is a rare form of secondary Raynaud's
      phenomenon in workers who frequently use the ulnar side of the palm as a hammer.
      Clinically the patient with HHS shows neurologic symptoms such as paresthesia,
      numbness and pain and signs of vascular insufficiency such as coldness, pallor,
      discoloration and blanching of the affected ulnar sided fingers. The diagnosis is
      verified by angiography, showing thrombosis or aneurysm of the distal ulnar
      artery. We report on the treatment and outcome of 5 patients with HHS. All
      patients were painfree after treatment. But with the ongoing working habit of
      using the hand as a hammer there is always the risk of a recurrence. Therefore
      the job environment has to be changed considerably and the most effort should go
      into prevention and prophylaxis. If the change of the working habit is not
      possible, the job is clearly at stake.

PMID- 12232743
TI  - [Technique of distal biceps tendon repair using a limited anterior approach].
AB  - From May 1999 to November 2001 an anatomical attachment of a ruptured distal
      biceps tendon to the radial tuberosity was performed through a limited anterior
      approach in 8 male patients with an age of 37 to 47 years. Through a small
      incision in the cubital fossa (3-4 cm) the remaining synovial sheet of the biceps
      tendon was followed to insert absorbable anchor hooks into the radial tuberosity.
      The distal biceps tendon then was anatomically reattached. Instruments for
      arthroscopic Bankart-repair were used. There were no specific complications like
      neurovascular damage or significant functional impairment. The contour of the
      biceps muscle was restored in all cases. 3 out of 7 patients developed mild
      heterotopic ossifications without functional deficits. In our experience the
      presented technique is a possible minimal invasive procedure of distal biceps
      tendon repair without major complications and with good functional results.

PMID- 12232744
TI  - [Coracoid pseudarthrosis caused by anterior shoulder dislocation with concomitant
      coracoid fracture].
AB  - Fractures of the coracoid process are rare and represent only 2-5% of all
      fractures of the scapula. The most frequent cause of a coracoid fracture is
      direct trauma, but indirect trauma may also lead to a fracture of this kind.
      Avulsion injuries as part of an acromioclavicular dislocation are the most
      frequent forms of trauma. For the rare cases of an anterior shoulder dislocation
      with concomitant coracoid fracture, two different mechanism are discussed. One
      cause of the coracoid fracture could be direct impact of the dislocated head of
      the humerus on the coracoid process, another may be the occurrence of a sudden
      strong pull of the muscles inserting at the coracoid process during shoulder
      dislocation.In the majority of cases, conservative treatment with six weeks of
      immobilization is appropriate. If a pseudarthrosis occurs and there is persistent
      pain, we recommend the operative fixation of the distal coracoid fragment by
      insertion of cancellous bone graft taken from the iliac crest and stabilization
      with a cannulated AO titanium small fragment screw and PDS cord.

PMID- 12232745
TI  - [Current recommendations for diagnosis and therapy of heparin-induced
      thrombocytopenia].
AB  - Thrombosis prophylaxis using heparins is mandatory in most trauma patients.
      However, heparins can induce heparin-induced thrombocytopenia (HIT), the most
      common and clinically important immune-mediated drug-dependent thrombocytopenia.
      Affected patients are at risk of developing new thromboembolic complications. HIT
      has to be considered if platelet counts decrease >50% between day 5-10 of heparin
      therapy that cannot be explained alternatively or if new thromboses occur in a
      sufficiently heparinised patient. Immediately changing the anticoagulant to
      danaparoid or lepirudin is most important. Proof of anti-platelet-factor
      4/heparin antibodies secures the diagnosis, usually retrospectively. Diagnosis
      and therapy are demonstrated in a typical HIT patient. HIT usually occurs in the
      second week of heparin administration. Heparin-reexposure within 100 days can
      lead to HIT before day 5. For early recognition of HIT, platelet counts should be
      monitored regularly. Because of earlier discharge of patients to rehabilitation
      or outpatient care, the problem of HIT-diagnosis and therapy gains increasing
      relevance in these sectors.

PMID- 12232746
TI  - [Intramedullary bone endoscopy (IBE). First results of experimental
      intramedullary endoscopy of long bone].
AB  - INTRODUCTION: Intramedullary preparation and endoscopy of long bone is not
      mentioned in literature. We present our first results of experimental
      intramedullary endoscopy of long bone. METHODS: Experimental tests were performed
      at 4 corpse bones (twice tibia, twice femur). RESULTS: Intramedullary endoscopy
      and preparation was possible in all cases. A good view for inspection of the
      medullary canal was achieved by using the endoscope (Wolf GmbH, Germany).
      CONCLUSION: Endoscopic preparation and intramedullary endoscopy in the long bone
      ist possible. By using the endoscopic tools, a "neocavum" for endoscopic
      manipulation could easily be created.

PMID- 12232747
TI  - Will early detection of non-axillary sentinel nodes affect treatment decisions?
AB  - Axillary lymph node involvement is the best prognostic factor for breast cancer
      survival. Staging breast cancers by axillary dissection remains standard
      management and is part of the UK national guidelines for breast cancer treatment.
      In the presence of involved axillary lymph nodes best treatment has been shown to
      be axillary clearance (Fentiman and Mansell, 1991), but clearly for women whose
      nodes are uninvolved avoidance of morbidity is optimal and this will be achieved
      by minimal dissection of the axilla. Thus, for node-negative women the
      introduction of the sentinel node biopsy technique may revolutionise the approach
      to the axilla. These will be women with mammographic screen detected small well
      and moderately differentiated tumours (Hadjiloucas and Bundred, 2000). The impact
      of sentinel node biopsy in women who have symptomatic large tumours is unproven,
      and around half of these women will require a second procedure to clear their
      axilla or radiotherapy as treatment. Even for those women found to have involved
      sentinel lymph nodes the ability to use early systemic chemotherapy followed by
      axillary clearance or radiotherapy may provide long-term survival gains. Sentinel
      node biopsy should not, however, become routine practice until randomised
      controlled trials have proven its benefit and safety in reducing morbidity.
      Several randomised controlled trials (including ALMANAC) are currently underway.

PMID- 12232748
TI  - The role of microvessel density on the survival of patients with lung cancer: a
      systematic review of the literature with meta-analysis.
AB  - In order to determine whether angiogenesis is a prognostic marker in lung cancer,
      we performed a systematic review of the literature to assess the prognostic value
      on survival of microvessel count in patients with lung cancer. Published studies
      were identified by an electronic search in order to aggregate survival results,
      after a methodological assessment using a quality scale designed by the European
      Lung Cancer Working Party. To be eligible, a study had to deal with microvessel
      count assessment in lung cancer patients on the primary site and to provide
      survival analysis according to microvessel count expression. Microvessel count
      has been assessed on surgical samples by immunohistochemistry using factor VIII
      in 14 studies, CD34 in 10 and CD31 in eight. Respectively 1866, 1440 and 1093 non
      small cell lung cancer patients were considered. The overall median quality
      scores were respectively 52, 59 and 59% for studies assessing microvessel count
      via factor VIII, CD34 and CD31, without significant difference between studies
      evaluable or not for meta-analysis nor between studies with significant or non
      significant results. Seven 'factor VIII' studies, nine 'CD34' and seven 'CD31'
      provided sufficient data allowing a meta-analysis on survival and were evaluable
      for results aggregation. This showed that a high microvessel count in the
      primitive lung tumour was a statistically significant poor prognostic factor for
      survival in non small cell lung cancer whatever it was assessed by factor VIII
      (HR: 1.81; 95% CI: 1.16-2.84), CD34 (HR: 1.99; 95% CI: 1.53-2.58) or CD31 (HR:
      1.80; 95% CI: 1.10-2.96). Variations in survival among the individual studies can
      be explained in addition to patients selection criteria by the heterogeneous
      methodologies used to stain and count microvessels: different antibody clones,
      identification of 'hotspots', Weidner or Chalkey counting method, cut-off
      selection. Microvessel count, reflecting the angiogenesis, appears to be a poor
      prognostic factor for survival in surgically treated non small cell lung cancer
      but standardisation of angiogenesis assessment by the microvessel count is
      necessary.

PMID- 12232749
TI  - Oxaliplatin, fluorouracil and leucovorin for advanced biliary system
      adenocarcinomas: a prospective phase II trial.
AB  - We studied the activity of combined oxaliplatin and fluorouracil-leucovorin in 16
      consecutive patients with advanced biliary tract adenocarcinomas. The disease
      control rate (responses and stable disease) was 56% (95% confidence interval, 29
      84%) and the median overall survival time was 9.5 months (range 0.9-26.8+).
      Therefore, this regimen might be active in biliary adenocarcinomas with further
      evaluation necessary.

PMID- 12232750
TI  - Impact of non-axillary sentinel node biopsy on staging and treatment of breast
      cancer patients.
AB  - The purpose of this study was to evaluate the occurrence of lymphatic drainage to
      non-axillary sentinel nodes and to determine the implications of this phenomenon.
      A total of 549 breast cancer patients underwent lymphoscintigraphy after
      intratumoural injection of (99m)Tc-nanocolloid. The sentinel node was
      intraoperatively identified with the aid of intratumoural administered patent
      blue dye and a gamma-ray detection probe. Histopathological examination of
      sentinel nodes included step-sectioning at six levels and immunohistochemical
      staining. A sentinel node outside level I or II of the axilla was found in 149
      patients (27%): internal mammary sentinel nodes in 86 patients, other non
      axillary sentinel nodes in 44 and both internal mammary and other non-axillary
      sentinel nodes in nineteen patients. The intra-operative identification rate was
      80%. Internal mammary metastases were found in seventeen patients and metastases
      in other non-axillary sentinel nodes in ten patients. Staging improved in 13% of
      patients with non-axillary sentinel lymph nodes and their treatment strategy was
      changed in 17%. A small proportion of clinically node negative breast cancer
      patients can be staged more precisely by biopsy of sentinel nodes outside level I
      and II of the axilla, resulting in additional decision criteria for postoperative
      regional or systemic therapy.

PMID- 12232751
TI  - Sentinel node detection in N0 cancer of the pharynx and larynx.
AB  - Neck lymph node status is the most important factor for prognosis in head and
      neck squamous cell carcinoma. Sentinel node detection reliably predicts the lymph
      node status in melanoma and breast cancer patients. This study evaluates the
      predictive value of sentinel node detection in 50 patients suffering from
      pharyngeal and laryngeal carcinomas with a N0 neck as assessed by ultrasound
      imaging. Following 99m-Technetium nanocolloid injection in the perimeter of the
      tumour intraoperative sentinel node detection was performed during lymph node
      dissection. Postoperatively the histological results of the sentinel nodes were
      compared with the excised neck dissection specimen. Identification of sentinel
      nodes was successful in all 50 patients with a sensitivity of 89%. In eight cases
      the sentinel node showed nodal disease (pN1). In 41 patients the sentinel node
      was tumour negative reflecting the correct neck lymph node status (pN0). We
      observed one false-negative result. In this case the sentinel node was free of
      tumour, whereas a neighbouring lymph node contained a lymph node metastasis
      (pN1). Although we have shown, that skipping of nodal basins can occur, this
      technique still reliably identifies the sentinel nodes of patients with squamous
      cell carcinoma of the pharynx and larynx. Future studies must show, if sentinel
      node detection is suitable to limit the extent of lymph node dissection in
      clinically N0 necks of patients suffering from pharyngeal and laryngeal squamous
      cell carcinoma.

PMID- 12232752
TI  - Phase II study to evaluate combining gemcitabine with flutamide in advanced
      pancreatic cancer patients.
AB  - A phase II study was undertaken to determine the safety of combining flutamide
      with gemcitabine, with response rate being the primary end point. Twenty-seven
      patients with histologically proven, previously untreated, unresectable
      pancreatic adenocarcinoma received gemcitabine, 1 g m(-2) intravenously on days
      1, 8 and 15 of a 28 day cycle, and flutamide 250 mg given orally three times
      daily. Treatment was halted if there was unacceptable toxicity, or evidence of
      disease progression. Toxicity was documented every cycle. Tumour assessment was
      undertaken after cycles 2 and 4, and thereafter at least every additional four
      cycles. One hundred and seventeen cycles of treatment were administered, median
      four cycles per patient (range 1-18). Gemcitabine combined with flutamide was
      well tolerated, with most toxicities being recorded as grade 1 or 2 and only nine
      treatment cycles associated with grade 3 toxicity. The most frequent toxicity was
      myelosuppression. One case of transient jaundice was recorded. The commonest
      symptomatic toxicity was nausea and vomiting. The response rate was 15% (four
      partial responses), median survival 6 months and 22% of patients were alive at 1
      year. These results suggest antitumour activity of the combination therapy to be
      equivalent to single agent gemcitabine.

PMID- 12232754
TI  - Serum insulin level, disease stage, prostate specific antigen (PSA) and Gleason
      score in prostate cancer.
AB  - In the present study, we assessed the relationship of serum insulin levels and
      three surrogate markers of recurrence, T stage, PSA, and Gleason score, in men
      with localized prostate cancer. Participants in our study were found through
      urology and radiation oncology clinics, and all eligible patients were asked to
      take part. All patients were asymptomatic and had been initially diagnosed on the
      basis of rising PSA or abnormal physical examination. Histological confirmation
      of diagnosis was obtained for all subjects. Serum insulin levels were determined
      by chemoluminescent assay with a standard, commercially available instrument.
      Patients were divided into three previously defined risk groups: Low risk: PSA <
      or =10, stage < or =T2a, or Gleason grade < or =6. Medium risk: 10 <PSA < or =15,
      Gleason 7 or stage T2b. High risk: Gleason >7, tumour in seminal vesicle biopsy,
      PSA >15 or stage T2c or T3. One hundred and sixty-three men with prostate cancer
      were studied. There was a significant increase in serum insulin with risk group
      (P=0.003, one way anova). Tukey's multiple range test showed that the insulin
      levels of high risk patients were significantly higher than the insulin levels of
      medium and low risk patients (P=0.05) but the insulin levels of medium and low
      risk patients were not significantly different from one another. Multivariate
      linear regression, with insulin as the dependent variable, Gleason score, PSA,
      and T stage (T1, T2, T3) as the independent variables, was significant overall
      (P<0.001, r(2)=0.120). Increased T stage was independently correlated with
      increased serum insulin levels (P<0.001). Gleason score was negatively,
      insignificantly correlated with serum insulin level (P=0.059). The positive
      correlation of PSA and insulin level was not significant (P=0.097). To assure
      normal distribution of insulin and PSA values, the regression was repeated with
      log (insulin) as the dependent variable, log (PSA), T stage (T1, T2, T3), and
      Gleason score as independent variables. The regression was significant overall
      (P=0.002, r(2) =0.095). Increased T stage was independently correlated with
      increased log (insulin level) (P=0.026). Gleason score was negatively,
      insignificantly correlated with log (insulin) level (P=0.728). The positive
      correlation of log (PSA) and log (insulin) levels was significant (P=0.010). The
      relationship between increased insulin level and advanced tumour stage in
      prostate cancer we describe here is biologically quite plausible, since insulin
      is a growth factor. Further studies may document whether serum insulin levels
      might be a useful biomarker of prostate cancer stage.

PMID- 12232753
TI  - Weekly epirubicin in patients with hormone-resistant prostate cancer.
AB  - The aim of this study was to investigate the benefit of weekly epirubicin in the
      treatment of metastatic hormone-resistant prostate cancer. One hundred and forty
      eight patients with metastatic hormone-resistant prostate cancer received weekly
      30-min intravenous infusions of epirubicin 30 mg m(2) of body surface area. The
      primary end-point was palliative response, defined as a reduction in pain
      intensity and an improvement in performance status. The secondary end-points were
      the duration of the palliative response, quality of life and survival. Fifty
      seven (44%) of the 131 evaluable patients met the primary criterion of palliative
      response after six treatment cycles and 73 (56%) after 12 cycles; the median
      duration of the response was 9 months (range 1-11). The median global quality of
      life improved in 52% of the patients after six cycles and in 68% after 12 cycles.
      The 12- and 18-month survival rates were respectively 56 and 31%, with a median
      survival of 13+ months (range 1-36). The treatment was well tolerated: grade 3
      neutropenia was observed in 8% of the patients, grade 3 anaemia in 7%, and grade
      3 thrombocytopenia in 3%. None of the patients developed grade 4 toxicity or
      congestive heart failure. Weekly epirubicin chemotherapy can lead to a rapid and
      lasting palliative result in patients with metastatic HRPC, and have a positive
      effect on the quality of life and survival.

PMID- 12232755
TI  - Irinotecan in patients with relapsed or cisplatin-refractory germ cell cancer: a
      phase II study of the German Testicular Cancer Study Group.
AB  - Despite generally high cure rates in patients with metastatic germ cell cancer,
      patients with progressive disease on first-line cisplatin-based chemotherapy or
      with relapsed disease following high-dose salvage therapy exhibit a very poor
      prognosis. Irinotecan has shown antitumour activity in human testicular tumour
      xenografts in nude mice. We have performed a phase II study examining the single
      agent activity of irinotecan in patients with metastatic relapsed or cisplatin
      refractory germ cell cancer. Refractory disease was defined as progression or
      relapse within 4 weeks after cisplatin-based chemotherapy or relapse after
      salvage high-dose chemotherapy with autologous stem cell support. Irinotecan was
      administered at a dose of 300 (-350) mg m(-2) every 3 weeks. Response was
      evaluated every 4 weeks. Fifteen patients have been enrolled. Median age was 35
      (19-53) years. Primary tumour localisation was gonadal/mediastinal in 12/3
      patients. Patients had been pretreated with a median of six (4-12) cisplatin
      containing cycles and 13 out of 15 patients had previously failed high-dose
      chemotherapy with blood stem cell support. Median number of irinotecan
      applications was two (1-3). Fourteen patients are assessable for response and all
      for toxicity. In one patient, no adequate response evaluation was performed.
      Toxicity was generally acceptable and consisted mainly of haematological side
      effects with common toxicity criteria 3 degrees anaemia (two patients), common
      toxicity criteria 3 degrees leukocytopenia (one patient) and common toxicity
      criteria 3 degrees thrombocytopenia (three patients). Common toxicity criteria
      3/4 degrees non-haematological toxicity occurred in five patients (33%): 1 x
      diarrhoea, 2 x alopecia, 1 x fever and in one patient worsening of pre-existing
      peripheral polyneuropathy from 1 degrees to 4 degrees. No response was observed
      to irinotecan therapy. Currently, 13 patients have died of the disease and two
      patients are alive with the disease. The patients included in our study exhibit
      similar prognostic characteristics as patients treated in previous trials
      evaluating new drugs in this setting. Irinotecan at a dose of 300-350 mg m(-2)
      every 3 weeks appears to have no antitumour activity in patients with cisplatin
      refractory germ cell cancer and, thus, further investigation in this disease is
      not justified.

PMID- 12232756
TI  - The imPaCT study: a randomised controlled trial to evaluate a hospital palliative
      care team.
AB  - A randomised controlled trial was undertaken to assess the effectiveness of a
      hospital Palliative Care Team (PCT) on physical symptoms and health-related
      quality of life (HRQoL); patient, family carer and primary care professional
      reported satisfaction with care; and health service resource use. The full
      package of advice and support provided by a multidisciplinary specialist PCT
      ('full-PCT') was compared with limited telephone advice ('telephone-PCT', the
      control group) in the setting of a teaching hospital trust in the SW of England.
      The trial recruited 261 out of 684 new inpatient referrals; 175 were allocated to
      'full-PCT', 86 to 'telephone-PCT' (2 : 1 randomisation); with 191 (73%) being
      assessed at 1 week. There were highly significant improvements in symptoms,
      HRQoL, mood and 'emotional bother' in 'full-PCT' at 1 week, maintained over the 4
      week follow-up. A smaller effect was seen in 'telephone-PCT'; there were no
      significant differences between the groups. Satisfaction with care in both groups
      was high and there was no significant difference between them. These data reflect
      a high standard of care of patients dying of cancer and other chronic diseases in
      an acute hospital environment, but do not demonstrate a difference between the
      two models of service delivery of specialist palliative care.

PMID- 12232758
TI  - Childhood solid tumours in relation to infections in the community in Cumbria
      during pregnancy and around the time of birth.
AB  - In a retrospective cohort study of all 99 976 live births in Cumbria, 1975-1992,
      we investigated whether higher levels of community infections during the mother's
      pregnancy and in early life were risk factors for solid tumours (brain/spinal and
      other tumours), diagnosed 1975-1993 under age 15 years. Logistic regression was
      used to relate risk to incidence of community infections in three prenatal and
      two postnatal quarters. There was an increased risk of brain/spinal tumours among
      children exposed around or soon after birth to higher levels of community
      infections, in particular measles (OR for trend=2.1, 95%CI : 1.3-3.6, P=0.008)
      and influenza (OR for exposure=3.3, 95%CI : 1.5-7.4, P=0.005). There was some
      evidence of an association between exposure to infections around and soon after
      birth and risk of other tumours, but this may have been a chance finding. The
      findings are consistent with other recent epidemiological studies suggesting
      brain tumours may be associated with perinatal exposure to infections.

PMID- 12232757
TI  - Population mixing and leukaemia in young people around the La Hague nuclear waste
      reprocessing plant.
AB  - In order to investigate for an association between population mixing and the
      occurrence of leukaemia in young people (less than 25 years), a geographical
      study was conducted, for the years 1979 to 1998, in Nord Cotentin (France). This
      area experienced between the years 1978 and 1992 a major influx of workers for
      the construction of a nuclear power station and a new nuclear waste reprocessing
      unit. A population mixing index was defined on the basis of the number of workers
      born outside the French department of 'La Manche' and living in each 'commune',
      the basic geographical unit under study. The analyses were done with indirect
      standardisation and Poisson regression model allowing or not for extra-Poisson
      variation. Urban 'communes' were considered as the reference population. The
      Incidence Rate Ratio was 2.7 in rural 'communes' belonging to the highest tertile
      of population mixing (95% Bayesian credible interval, 95%BCI=1.2-5.9). A positive
      trend was observed among rural strata with increasing population mixing index
      (IRR for trend=1.4, 95%BCI=1.1-1.8). The risk became stronger for Acute
      Lymphoblastic Leukaemia in children 1-6 years old in the highest tertile of
      population mixing (IRR=5.5, 95%BCI=1.4-23.3). These findings provide further
      support for a possible infective basis of childhood leukaemia.

PMID- 12232759
TI  - N-acetylgalactosaminyl transferase-3 is a potential new marker for non-small cell
      lung cancers.
AB  - N-acetylgalactosaminyl transferase-3 (GalNAc-T3) is an enzyme involved in the
      initial glycosylation of mucin-type O-linked proteins. In the present study, we
      used immunohistochemistry to examine GalNAc-T3 expression in 215 surgically
      resected non-small cell lung cancers. We analysed the biological and clinical
      importance of GalNAc-T3 expression, especially with regard to its potential as a
      prognostic factor. We found that normal bronchial epithelial cells, bronchial
      gland cells, and alveolar pneumocytes showed cytoplasmic immunostaining for
      GalNAc-T3. Low expression of GalNAc-T3, observed in 93 of 215 tumours (43.4%),
      was found more frequently in tumours from smokers than those from nonsmokers
      (P=0.001), in squamous cell carcinomas than nonsquamous cell carcinomas
      (P<0.0001), and in moderately and poorly differentiated tumours than well
      differentiated tumours (P=0.0002). Multivariate logistic regression analysis
      showed that an association of low GalNAc-T3 expression with squamous cell
      carcinomas was the only one significant relationship of GalNAc-T3 expression with
      various factors (P<0.0001). Moreover, tumours losing GalNAc-T3 expression had a
      significantly higher Ki-67 labelling index than tumours retaining GalNAc-T3
      expression (P=0.0003). Patients with low GalNAc-T3 expression survived a
      significantly shorter time than patients with high GalNAc-T3 expression in 103
      pStage I non-small cell lung cancers (5-year survival rates, 58% and 78%,
      respectively; P=0.02 by log-rank test) as well as in 61 pStage I nonsquamous cell
      carcinomas (5-year survival rates, 63% and 85%, respectively; P=0.03). Low GalNAc
      T3 expression was an unfavourable prognostic factor in pStage I non-small cell
      lung cancers (hazards ratio, 2.04; P=0.03), and in pStage I nonsquamous cell
      carcinomas (hazards ratio, 2.70; P=0.03). These results suggest that GalNAc-T3 is
      a new marker of non-small cell lung cancers with specificity for histology and
      prognosis.

PMID- 12232760
TI  - Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel
      is associated with good prognosis.
AB  - Progression of colorectal cancer may follow either of two main genetic routes:
      the chromosome- or microsatellite-instability pathways. Association between the
      patients' prognosis and microsatellite instability has been questioned. Improved
      survival has previously been found in patients with expression of HLA-DR antigens
      on their tumour cells. In this study, the expression of HLA-DR antigen was
      investigated by immunohistochemistry in 357 large bowel carcinomas stratified by
      microsatellite instability status. Sixteen per cent of the tumours showed strong
      HLA-DR expression and 35% had weak DR expression. We confirmed that patients with
      strong positive HLA-DR staining had improved survival (P<0.001) compared to
      patients with no HLA-DR expression. Strong epithelial HLA-DR staining was
      significantly associated with high level of microsatellite instability (P<0.001).
      In the subgroup of tumours with characteristics typical of the chromosomal
      instability phenotype, i.e. in microsatellite-stable tumours, the patients
      positive for the HLA-DR determinants showed better survival than those without
      HLA-DR expression. The protective effect of HLA-DR expression on survival was
      confirmed by multivariate analysis, both in the whole patient group and in the
      microsatellite-stable/microsatellite instability-low group. This might be
      explained by enhanced T-cell mediated anti-tumour immune responses against tumour
      cells in the HLA-DR positive tumours. The finding of better patient survival in
      the subgroup of strong HLA-DR positive microsatellite-stable tumours may have
      clinical implications for these patients.

PMID- 12232761
TI  - Immunofluorometric quantitation and histochemical localisation of kallikrein 6
      protein in ovarian cancer tissue: a new independent unfavourable prognostic
      biomarker.
AB  - Human kallikrein 6 protein is a newly discovered human kallikrein. We determined
      the amount of human kallikrein 6 in extracts of 182 ovarian tumours and
      correlated specific activity (ng hK6 mg(-1) total protein) with
      clinicopathological variables documented at the time of surgical excision and
      with outcome (progression free survival, overall survival) monitored over a
      median interval of 62 months. Thirty per cent of the tumours were positive for
      human kallikrein 6 (>35 ng hK6 mg(-1) total protein). Human kallikrein 6-specific
      immunohistochemical staining of four ovarian tissues that included benign,
      borderline and malignant lesions indicated a cytoplasmic location of human
      kallikrein 6 in tumour cells of epithelial origin, although the intensity of
      staining was variable. Tumour human kallikrein 6 (ng hK6 mg(-1) total protein)
      was higher in late stage disease, serous histotype, residual tumour >1 cm and
      suboptimal debulking (>1 cm) (P<0.05). Univariate analysis revealed that patients
      with tumour human kallikrein 6 positive specific activity were more likely to
      suffer progressive disease and to die (hazard ratio 1.71 (P=0.015) and 1.88
      (P=0.022), respectively). Survival curves demonstrated the same (P=0.013 and
      0.019, respectively). Multivariate analysis revealed that human kallikrein 6
      positivity was retained as an independent prognostic variable in several
      subgroups of patients, namely those with (low) grade I and II tumours (hazard
      ratio progression free survival 4.3 (P=0.027) and overall survival 4.1 (P=0.023))
      and those with optimal debulking (hazard ratio progression free survival 3.8
      (P=0.019) and overall survival 5.6 (P=0.011)). We conclude that tumour kallikrein
      6 protein levels have utility as an independent adverse prognostic marker in a
      subgroup of ovarian cancer patients with otherwise apparently good prognosis.

PMID- 12232762
TI  - The prognostic value of vascular endothelial growth factor in 574 node-negative
      breast cancer patients who did not receive adjuvant systemic therapy.
AB  - The growth and metastasising capacity of solid tumours are dependent on
      angiogenesis. Vascular endothelial growth factor is a mediator of angiogenesis.
      In this study we investigated whether vascular endothelial growth factor is
      associated with the natural course of the disease in primary invasive breast
      cancer. In 574 tumours of patients with node-negative invasive breast cancer the
      cytosolic levels of vascular endothelial growth factor were measured using a
      quantitative enzyme-linked immunosorbent assay. These patients did not receive
      adjuvant systemic therapy and were followed for a median follow-up time of 61
      months (range 2-155 months) after the primary diagnosis. Correlations with well
      known prognostic factors, and univariate and multivariate survival analyses were
      performed. Vascular endothelial growth factor level was positively associated
      with age and tumour size (P=0.042 and P=0.029, respectively). In addition,
      vascular endothelial growth factor level was inversely, but weakly correlated
      with progesterone receptor levels (PgR) (r(s)=-0.090, P=0.035). A high vascular
      endothelial growth factor level (equal or above the median level of 0.53 ng mg(
      1) protein) predicted a reduced relapse-free survival and overall survival in the
      univariate survival rate analysis (for both P=0.005). In the multivariate
      analysis as well, vascular endothelial growth factor showed to be an independent
      predictor of poor relapse-free survival and overall survival (P=0.045 and
      P=0.029, respectively), in addition to age, tumour size and PgR. The results show
      that cytosolic levels of vascular endothelial growth factor in tumour tissue
      samples are independently indicative of prognosis for patients with node-negative
      breast cancer who were not treated with adjuvant systemic therapy. This implies
      that vascular endothelial growth factor is related with the natural course of
      breast cancer progression.

PMID- 12232763
TI  - High level amplification of N-MYC is not associated with adverse histology or
      outcome in primary retinoblastoma tumours.
AB  - Twenty-five primary retinoblastoma tumours were analysed by real-time
      quantitative polymerase chain reaction to determine the genomic copy number of
      the N-MYC gene (2p24) relative to the copy number for REL, B2M, ALB, AF10 and
      MLL. Twenty-one of these tumours were shown by Comparative Genomic Hybridization
      to contain variable copy number increases of chromosomal material mapping to 2p.
      High level amplification (>30-fold) of N-MYC was found in three tumours, none of
      which showed adverse histological features and all patients are surviving at
      between 54 and 108 months post enucleation. Furthermore, the three tumours
      associated with metastasis and adverse patient outcome showed normal N-MYC copy
      number. Although high level amplification of N-MYC is an unfavourable prognostic
      indicator in neuroblastoma, these data show no evidence of a correlation between
      amplification of N-MYC and adverse outcome in retinoblastoma.

PMID- 12232764
TI  - Use of radiolabelled choline as a pharmacodynamic marker for the signal
      transduction inhibitor geldanamycin.
AB  - There is an urgent need to develop non-invasive pharmacodynamic endpoints for the
      evaluation of new molecular therapeutics that inhibit signal transduction. We
      hypothesised that, when labelled appropriately, changes in choline kinetics could
      be used to assess geldanamycin pharmacodynamics, which involves inhibition of the
      HSP90 molecular chaperone-->Raf1-->Mitogenic Extracellular Kinase-->Extracellular
      Signal-Regulated Kinase 1 and 2 signal transduction pathway. Towards identifying
      a potential pharmacodynamic marker response, we have studied radiolabelled
      choline metabolism in HT29 human colon carcinoma cells following treatment with
      geldanamycin. We studied the effects of geldanamycin, on net cellular
      accumulation of (methyl-(14)C)choline and (methyl-(14)C)phosphocholine
      production. In parallel experiments, the effects of geldanamycin on extracellular
      signal-regulated kinase 1 and 2 phosphorylation and cell viability were also
      assessed. Additional validation studies were carried out with the mitogenic
      extracellular kinase inhibitor U0126 as a positive control; a cyclin-dependent
      kinase-2 inhibitor roscovitine and the phosphatidylinositol 3-kinase inhibitor
      LY294002 as negative controls. Hemicholinium-3, an inhibitor of choline transport
      and choline kinase activity was included as an additional control. In
      exponentially growing HT29 cells, geldanamycin inhibited extracellular signal
      regulated kinase 1 and 2 phosphorylation in a concentration- and time-dependent
      manner. These changes were associated with a reduction in (methyl-(14)C)choline
      uptake, (methyl-(14)C) phosphocholine production and cell viability. Brief
      exposure to U0126, suppressed phosphocholine production to the same extent as
      Hemicholinium-3. In contrast to geldanamycin and U0126, which act upstream of
      extracellular signal-regulated kinase 1 and 2, roscovitine and LY294002 failed to
      suppress phosphocholine production. Our results suggest that when labelled with
      carbon-11 isotope, (methyl-(11)C)choline may be a useful pharmacodynamic marker
      for the non-invasive evaluation of geldanamycin analogues.

PMID- 12232765
TI  - ALA and ALA hexyl ester induction of porphyrins after their systemic
      administration to tumour bearing mice.
AB  - The use of synthetic lipophilic molecules derived from 5-aminolevulinic acid
      (ALA) is currently under investigation to enhance cellular ALA penetration. In
      this work we studied the effect of systemic administration to mice of the hexyl
      ester of ALA (He-ALA) on porphyrin tissue synthesis as compared to ALA. In most
      normal tissues as well as in tumour, He-ALA induced less porphyrin synthesis than
      ALA after its systemic administration either intravenous or intraperitoneal,
      although explant organ cultures exposed to either ALA or He-ALA revealed equally
      active esterases. The only tissue that accumulated higher porphyrin levels from
      He-ALA (seven times more than ALA) was the brain, and this correlated well with a
      rapid increase in ALA/He-ALA content in brain after administration of He-ALA.
      This may be ascribed to a differential permeability to lipophilic substances
      controlled by the blood-brain barrier, a feature which could be further exploited
      to treat brain tumours.

PMID- 12232766
TI  - Detection of peptide-specific CTL-precursors in peripheral blood lymphocytes of
      cancer patients.
AB  - Development of therapeutic vaccines is one of the major areas of tumour
      immunotherapy today. However, clinical trials of peptide-based cancer vaccines
      have rarely resulted in tumour regression. This failure might be due to an
      insufficient induction of cytotoxic T lymphocytes in the current regimes, in
      which cytotoxic T lymphocytes-precursors in pre-vaccination peripheral blood
      mononuclear cells are not measured. Initiation of immune-boosting through
      vaccination could be better than that of immune-priming with regard to induction
      of prompt and strong immunity. If this is also the case for therapeutic vaccines,
      pre-vaccination measurement of peptide-specific cytotoxic T lymphocytes
      precursors will be important. In the present study, we investigated whether
      cytotoxic T lymphocytes-precursors reacting to 28 kinds of peptides of vaccine
      candidates (13 and 15 peptides for HLA-A24(+) and HLA-A2(+) patients,
      respectively) were detectable in pre-vaccination peripheral blood mononuclear
      cells of 80 cancer patients. Peptide-specific cytotoxic T lymphocytes-precursors
      were found to be detectable in peripheral blood mononuclear cells of the majority
      of cancer patients (57 out of 80 cases, 71%). The mean numbers of positive
      peptides were 2.0 peptides per positive case. Peripheral blood mononuclear cells
      incubated with positive peptides, not with negative peptides, showed significant
      levels of HLA-class-I-restricted cytotoxicity to cancer cells. The profiles of
      positive peptides entirely varied among patients, and were not influenced by the
      cancer origin. These results may provide a scientific basis for the development
      of a new approach to cancer immunotherapy, e.g.) cytotoxic T lymphocytes
      precursor-oriented peptide vaccine.

PMID- 12232770
TI  - TNFalpha: kill or cure for demyelinating disease?

PMID- 12232771
TI  - Immunological research in clinical psychiatry: report on the consensus debate
      during the 7th Expert Meeting on Psychiatry and Immunology.
AB  - There is convincing evidence that cytokines are involved in the physiology and
      pathophysiology of brain function and interact with different neurotransmitter
      and neuroendocrine pathways. The possible involvement of the immune system in the
      neurobiological mechanisms that underlie psychiatric disorders has attracted
      increasing attention in recent years. Thus in the last decade, numerous clinical
      studies have demonstrated dysregulated immune functions in patients with
      psychiatric disorders. Such findings formed the basis of the 7th Expert Meeting
      on Psychiatry and Immunology in Muenster, Germany, where a consensus symposium
      was held to consider the strengths and weaknesses of current research in
      psychoneuroimmunology. Following a general overview of the field, the following
      topics were discussed: (1) methodological problems in laboratory procedures and
      recruitment of clinical samples; (2) the importance of pre-clinical research and
      animal models in psychiatric research; (3) the problem of statistical vs
      biological relevance. It was concluded that, despite a fruitful proliferation of
      research activities throughout the last decade, the continuous elaboration of
      methodological standards including the implementation of hypothesis-driven
      research represents a task that is likely to prove crucial for the future
      development of immunology research in clinical psychiatry.

PMID- 12232767
TI  - Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: mechanism of cell
      death.
AB  - Nutrient deprivation has been shown to cause cancer cell death. To exploit
      nutrient deprivation as anti-cancer therapy, we investigated the effects of the
      anti-metabolite 2-deoxy-D-glucose on breast cancer cells in vitro. This compound
      has been shown to inhibit glucose metabolism. Treatment of human breast cancer
      cell lines with 2-deoxy-D-glucose results in cessation of cell growth in a dose
      dependent manner. Cell viability as measured by the 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl tetrazolium bromide conversion assay and clonogenic survival are
      decreased with 2-deoxy-D-glucose treatment indicating that 2-deoxy-D-glucose
      causes breast cancer cell death. The cell death induced by 2-deoxy-D-glucose was
      found to be due to apoptosis as demonstrated by induction of caspase 3 activity
      and cleavage of poly (ADP-ribose) polymerase. Breast cancer cells treated with 2
      deoxy-D-glucose express higher levels of Glut1 transporter protein as measured by
      Western blot analysis and have increased glucose uptake compared to non-treated
      breast cancer cells. From these results we conclude that 2-deoxy-D-glucose
      treatment causes death in human breast cancer cell lines by the activation of the
      apoptotic pathway. Our data suggest that breast cancer cells treated with 2-deoxy
      D-glucose accelerate their own demise by initially expressing high levels of
      glucose transporter protein, which allows increased uptake of 2-deoxy-D-glucose,
      and subsequent induction of cell death. These data support the targeting of
      glucose metabolism as a site for chemotherapeutic intervention by agents such as
      2-deoxy-D-glucose.

PMID- 12232772
TI  - Association studies in psychiatric genetics: what are we doing?

PMID- 12232773
TI  - Association of the gamma-aminobutyric acid A receptor gene cluster with alcohol
      dependence in Taiwanese Han.

PMID- 12232774
TI  - Serotonin transporter gene and obese females with impulsivity.

PMID- 12232776
TI  - NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine
      D(2) and serotonin 5-HT(2)receptors-implications for models of schizophrenia.
AB  - Ketamine and PCP are commonly used as selective NMDA receptor antagonists to
      model the putative hypoglutamate state of schizophrenia and to test new
      antipsychotics. Recent findings question the NMDA receptor selectivity of these
      agents. To examine this further, we measured the affinity of ketamine and PCP for
      the high-affinity states of the dopamine D(2) and serotonin 5-HT(2) receptor and
      found that ketamine shows very similar affinity at the NMDA receptor and D(2)
      sites with a slightly lower affinity for 5-HT(2) (0.5 microM, 0.5 microM and 15
      microM respectively), while PCP shows similar affinity for the NMDA and 5-HT(2)
      sites, with a slightly lower affinity for the D(2) site (2 microM, 5 microM and
      37 microM respectively). Further, ketamine and PCP in clinically relevant doses
      caused a significant increase in the incorporation of [(35)S]GTP-gamma-S binding
      in CHO-cells expressing D(2) receptors, which was prevented by raclopride,
      suggesting a partial agonist effect at the D(2) receptor. Thus, ketamine and PCP
      may not produce a selective hypoglutamate state, but more likely produce a non
      selective multi-system neurochemical perturbation via direct and indirect
      effects. These findings confound the inferences one can draw from the
      ketamine/PCP models of schizophrenia.

PMID- 12232775
TI  - Serotonin transporter promoter variants in autism: functional effects and
      relationship to platelet hyperserotonemia.
AB  - The well-replicated platelet hyperserotonemia of autism has stimulated interest
      in serotonin (5-HT) in autism. We have examined the effects of the serotonin
      transporter gene (5-HTT, locus SLC6A4) promoter polymorphism (5-HTTLPR) on
      platelet 5-HT physiology in autism. Platelet 5-HT uptake rates and affinities
      (V(max) and K(m)), uptake site densities (B(max)) and 5-HT levels were examined
      in 31 French individuals with autism genotyped with respect to the 5-HTTLPR.
      Platelet 5-HT uptake and 5-HT levels were measured using HPLC; uptake sites were
      determined by radioligand binding. A 1.5-fold increased rate (V(max)) of platelet
      5-HT uptake was observed in ll genotype individuals compared to those with ls and
      ss genotypes (Mann- Whitney U-test, P = 0.022). However, no significant
      relationship was observed between genotype and uptake site density (U-test, P =
      0.51). Although median levels of platelet 5-HT in platelet-rich plasma were
      higher in the ll group, only trend level significance was observed (U-test, P=
      0.069); platelet 5-HT content measured in whole blood was similar across
      genotypes. Uptake rates were well correlated with B(max) values (r = 0.66, P =
      0.002); correlations between uptake and platelet 5-HT levels and between B(max)
      values and 5-HT levels were somewhat lower. While 5-HTTLPR alleles had an
      appreciable effect on platelet 5-HT uptake rates, effects on 5-HT levels and
      uptake site density were smaller or absent. Based on these preliminary data and
      prior studies of allele frequencies, we conclude that the 5-HTTLPR is not a major
      determinant of the group mean platelet serotonin elevation seen in autism.
      However, a role for increased uptake in the hyperserotonemia of autism can not be
      ruled out. In addition, it appears that studies of platelet 5-HT measures in
      autism and other disorders should take account of the effects of 5-HTTLPR
      genotype on 5-HT uptake

PMID- 12232777
TI  - Chronic lithium downregulates cyclooxygenase-2 activity and prostaglandin E(2)
      concentration in rat brain.
AB  - Rats treated with lithium chloride for 6 weeks have been reported to demonstrate
      reduced turnover of arachidonic acid (AA) in brain phospholipids, and decreases
      in mRNA and protein levels, and enzyme activity, of AA-selective cytosolic
      phospholipase A(2)(cPLA(2)). We now report that chronic lithium administration to
      rats significantly reduced the brain protein level and enzyme activity of
      cyclooxygenase-2 (COX-2), without affecting COX-2 mRNA. Lithium also reduced the
      brain concentration of prostaglandin E(2) (PGE(2)), a bioactive product of AA
      formed via the COX reaction. COX-1 and the Ca(2+)-independent iPLA(2) (type VI)
      were unaffected by lithium. These and prior results indicate that lithium targets
      a part of the AA cascade that involves cPLA(2) and COX-2. This effect may
      contribute to lithium's therapeutic action in bipolar disorder.

PMID- 12232778
TI  - A genome screen of 13 bipolar affective disorder pedigrees provides evidence for
      susceptibility loci on chromosome 3 as well as chromosomes 9, 13 and 19.
AB  - Bipolar affective disorder is a severe mood disorder that afflicts approximately
      1% of the population worldwide. Twin and adoption studies have indicated that
      genetic factors contribute to the disorder and while many chromosomal regions
      have been implicated, no susceptibility genes have been identified. We undertook
      a combined analysis of 10 cM genome screen data from a single large bipolar
      affective disorder pedigree, for which we have previously reported linkage to
      chromosome 13q14 (Badenhop et al, 2001) and 12 pedigrees independently screened
      using the same 400 microsatellite markers. This 13 pedigree cohort consisted of
      231 individuals, including 69 affected members. Two-point LOD score analysis was
      carried out under heterogeneity for three diagnostic and four genetic models. Non
      parametric multipoint analysis was carried out on regions of interest. Two-point
      heterogeneity LOD scores (HLODs) greater than 1.5 were obtained for 11 markers
      across the genome, with HLODs greater than 2.0 obtained for four of these
      markers. The strongest evidence for linkage was at 3q25-26 with a genome-wide
      maximum score of 2.49 at D3S1279. Six markers across a 50 cM region at 3q25-26
      gave HLODs greater than 1.5, with three of these markers producing scores greater
      than 2.0. Multipoint analysis indicated a 20 cM peak between markers D3S1569 and
      D3S1614 with a maximum NPL of 2.8 (P = 0.004). Three other chromosomal regions
      yielded evidence for linkage: 9q31-q33, 13q14 and 19q12-q13. The regions on
      chromosomes 3q and 13q have previously been implicated in other bipolar and
      schizophrenia studies. In addition, several individual pedigrees gave LOD scores
      greater than 1.5 for previously reported bipolar susceptibility loci on
      chromosomes 18p11, 18q12, 22q11 and 8p22-23.

PMID- 12232779
TI  - Dopamine D4 receptor and tyrosine hydroxylase genes in bipolar disorder: evidence
      for a role of DRD4.
AB  - The involvement of the mesocorticolimbic dopamine system in behaviors that are
      compromised in patients with mood disorder has led to the investigation of
      dopamine system genes as candidates for bipolar disorder. In particular, the
      functional VNTRs in the exon III of the dopamine D4 (DRD4) and in intron I of the
      tyrosine hydroxylase (TH) genes have been investigated in numerous association
      studies that have produced contrasting results. Likewise, linkage studies in
      multiplex bipolar families have shown both positive and negative results for
      markers in close proximity to DRD4 and TH on 11p15.5. We performed a linkage
      disequilibrium analysis of the DRD4 and TH VNTRs in a sample of 145 nuclear
      families comprised of DSM-IV bipolar probands and their biological parents. An
      excess of transmissions and non transmissions was observed for the DRD4 4- and 2
      repeat alleles respectively. The biased transmission showed a parent of origin
      effect (POE) since it was derived almost exclusively from the maternal meiosis (4
      repeat allele maternally transmitted 40 times vs 20 times non-transmitted; chi(2)
      = 6.667; df = 1; P = 0.009; while paternally transmitted 26 times vs 21 times non
      transmitted; chi(2) = 0.531; df = 1; P = 0.46). The analysis of TH did not reveal
      biased transmission of intron I VNTR alleles. Although replication of our study
      is necessary, the fact that DRD4 exhibit POE and is located on 11p15.5, in close
      proximity to a cluster of imprinted genes, suggests that genomic imprinting may
      be operating in bipolar disorder.

PMID- 12232780
TI  - A transcript map encompassing a susceptibility locus for bipolar affective
      disorder on chromosome 4q35.
AB  - Bipolar affective disorder is one of the most common mental illnesses with a
      population prevalence of approximately 1%. The disorder is genetically complex,
      with an increasing number of loci being implicated through genetic linkage
      studies. However, the specific genetic variations and molecules involved in
      bipolar susceptibility and pathogenesis are yet to be identified. Genetic linkage
      analysis has identified a bipolar disorder susceptibility locus on chromosome
      4q35, and the interval harbouring this susceptibility gene has been narrowed to a
      size that is amenable to positional cloning. We have used the resources of the
      Human Genome Project (HGP) and Celera Genomics to identify overlapping sequenced
      BAC clones and sequence contigs that represent the region implicated by linkage
      analysis. A combination of bioinformatic tools and laboratory techniques have
      been applied to annotate this DNA sequence data and establish a comprehensive
      transcript map that spans approximately 5.5 Mb. This map encompasses the
      chromosome 4q35 bipolar susceptibility locus, which localises to a "most
      probable" candidate interval of approximately 2.3 Mb, within a more conservative
      candidate interval of approximately 5 Mb. Localised within this map are 11
      characterised genes and eight novel genes of unknown function, which together
      provide a collection of candidate transcripts that may be investigated for
      association with bipolar disorder. Overall, this region was shown to be very gene
      poor, with a high incidence of pseudogenes, and redundant and novel repetitive
      elements. Our analysis of the interval has demonstrated a significant difference
      in the extent to which the current HGP and Celera sequence data sets represent
      this region.

PMID- 12232781
TI  - Neuronal overexpression of "readthrough" acetylcholinesterase is associated with
      antisense-suppressible behavioral impairments.
AB  - Molecular origin(s) of the diverse behavioral responses to anticholinesterases
      were explored in behaviorally impaired transgenic (Tg) FVB/N mice expressing
      synaptic human acetylcholinesterase (hAChE-S). Untreated hAChE-S Tg, unlike naive
      FVB/N mice, presented variably intense neuronal overexpression of the
      alternatively spliced, stress-induced mouse "readthrough" mAChE-R mRNA. Both
      strains displayed similar diurnal patterns of locomotor activity that were
      impaired 3 days after a day-to-night switch. However, hAChE-S Tg, but not FVB/N
      mice responded to the circadian switch with irregular, diverse bursts of
      increased locomotor activity. In social recognition tests, controls displayed
      short-term recognition, reflected by decreased exploration of a familiar,
      compared to a novel juvenile conspecific as well as inverse correlation between
      social recognition and cortical and hippocampal AChE specific activities. In
      contrast, transgenics presented poor recognition, retrievable by
      tetrahydroaminoacridine (tacrine, 1.5 mg kg(-1)). Tacrine's effect was short
      lived (24 h) suppression of the abnormal social recognition pattern in
      transgenics. Efficacy of antisense treatment was directly correlated with AChE-R
      levels and the severity of the impaired phenotype, being most apparent in
      transgenics presenting highly abnormal pre-treatment behavior. These findings
      demonstrate that neuronal AChE-R overproduction is involved in various behavioral
      impairments and anticholinesterase responses, and point to the antisense strategy
      as a potential approach for re-establishing cholinergic balance.

PMID- 12232782
TI  - Variation at the APOE -491 promoter locus is associated with altered brain levels
      of apolipoprotein E.
AB  - The apolipoprotein E (APOE, gene; apoE, protein) type 4 isoform is a well
      established risk factor for late-onset Alzheimer's disease (AD), and new data
      suggest that APOE promoter polymorphisms might also modulate AD risk, perhaps by
      altering transcription of the APOE gene. The current study was undertaken to
      determine whether the presence of the APOE promoter -491AA genotype (that appears
      to increase the risk for AD) is associated with an increase in the levels of apoE
      in brain tissue. Among 40 control and 20 autopsy-confirmed AD brain samples,
      levels of apoE were increased in the frontal cortex of AD cases (P < 0.001),
      consistent with the well-recognized up-regulation of APOE expression in reactive
      astrocytes. Among controls, the -491A allele appeared to impart a gene dose
      dependent effect on the levels of apoE in frontal cortex. The levels of apoE in
      the brains of AD patients with the -491AA genotype were increased as compared to
      control subjects with the same genotype (P< 0.001). These data support the notion
      that the -491AA APOE promoter genotype is associated with elevated brain
      apolipoprotein E levels, suggesting that the risk for AD may be modulated by the
      apoE protein level as well as by the apoE protein isoform.

PMID- 12232783
TI  - Regulatory region variability in the human presenilin-2 (PSEN2) gene: potential
      contribution to the gene activity and risk for AD.
AB  - We have analyzed the 5'-upstream promoter region of the presenilin 2 gene (PSEN2)
      for regulatory elements and examined Alzheimer disease (AD) patients and non
      demented individuals for polymorphisms in the 5' upstream promoter region of the
      PSEN2 gene. Direct sequencing analysis detected a common single adenine (A)
      nucleotide deletion polymorphism in the upstream promoter region of the PSEN2
      gene. Examination of cohorts of AD patients and age-matched control individuals
      revealed no statistically significant differences in the frequency of this
      polymorphism when compared with the total sample of AD patients and control
      individuals. However, subgroup and regression analysis suggested that the
      relatively rare -A/-A genotype increases risk of AD among subjects lacking
      apolipoprotein E (APOE) epsilon4 and among persons ages 65 years and younger. DNA
      sequence and DNA-protein binding analysis demonstrated that this mutation negates
      binding with putative repressor transcription factor (TF), interferon regulatory
      factor 2 (IRF2), in nuclear extracts prepared from the aged human brain
      neocortex. However this mutation creates a potential regulatory element,
      C/EBPbeta, that is responsive to pro-inflammatory (PI) induction. The expression
      activity assay with luciferase reporter gene into normal human neural progenitor
      cells in primary culture shows that the mutant PSEN2 regulatory region exhibits a
      1.8-fold higher level of basal expression and is sensitive to IL-1beta and
      Abeta42, but that it is synergistically induced 3.2-fold over the wild-type PSEN2
      by [IL-1beta+Abeta42]. These results suggest that under Pl and oxygen stress
      conditions relatively minor variations in PSEN2 promoter DNA sequence structure
      can enhance PSEN2 gene expression and that consequently these may play a role in
      the induction and/or proliferation of a Pl response in AD brain.

PMID- 12232784
TI  - Polymorphism in the cholesterol 24S-hydroxylase gene is associated with
      Alzheimer's disease.
AB  - Cholesterol and 24S-hydroxycholesterol are involved in the pathogenesis of
      Alzheimer's disease (AD). Increased serum cholesterol concentrations have been
      detected in patients with AD. 24S-Hydroxycholesterol is the primary cholesterol
      elimination product of the brain and possesses neurotoxic properties in vitro.
      The enzyme catalyzing the conversion of cholesterol to 24S-hydroxycholesterol,
      cholesterol 24S-hydroxylase (CYP46), is mainly expressed in neurons.
      Concentrations of 24S-hydroxycholesterol in cerebrospinal fluid (CSF) and serum
      differ significantly between AD patients and non-demented subjects. To test the
      hypothesis if polymorphisms in the CYP46 gene might influence the function of the
      respective enzyme and thus cholesterol metabolism in the human brain, we screened
      for polymorphisms in 114 AD patients and 144 healthy controls. Two intronic
      single nucleotide polymorphisms were observed and their allelic distribution was
      investigated. In our study sample, carriers of the C allele of the IVS3+43C --> T
      polymorphism were more prevalent in the group of AD patients than in healthy
      controls, while another IVS2-150A --> G polymorphism did not show a significant
      association with AD. The CC genotype of the IVS3+43C --> T polymorphism was
      associated with an increased 24S-hydroxycholesterol/cholesterol ratio in the CSF
      of AD patients. Our results indicate that the CYP46 gene locus may predispose to
      AD by increasing the 24S-hydroxycholesterol/cholesterol ratio in the brain.

PMID- 12232785
TI  - Association between the dopamine transporter gene and posttraumatic stress
      disorder.
AB  - Posttraumatic stress disorder (PTSD) is a chronic anxiety disorder that follows
      exposure to extreme events. A large twin study of Vietnam veterans had
      demonstrated a significant genetic contribution to chronic PTSD upon exposure to
      combat.(1,2) The underlying genes, however, have not been described. Given
      previous findings of abnormal dopamine (DA) function in PTSD, and given the
      putative effect of dopamine neurotransmission in shaping the responses to stress
      in animals, this study examined the association of the dopamine transporter (DAT)
      SLC6A3 3' variable number tandem repeat (VNTR) polymorphism with PTSD. The study
      evaluated 102 chronic PTSD patients and 104 carefully-documented trauma survivors
      (TS) who did not develop PTSD. Significant excess of 9 repeat allele was observed
      among PTSD patients (43% vs 30.5% in TS controls; chi(2) = 6.3, df = 1, P =
      0.012). An excess of 9 repeat homozygous genotype was also observed in PTSD
      (20.43% in PTSD vs 9.47% in TS controls; chi(2) = 6.11, df = 2, P < 0.047). These
      findings suggest that genetically determined changes in dopaminergic reactivity
      may contribute to the occurrence of PTSD among trauma survivors.

PMID- 12232786
TI  - Evidence that variation at the serotonin transporter gene influences
      susceptibility to attention deficit hyperactivity disorder (ADHD): analysis and
      pooled analysis.
AB  - Reduced central serotonergic activity has been implicated in poor impulse
      regulation and aggressive behaviour in animals, adults and also young
      children.(1,2) Two recently published studies have implicated variation at a
      polymorphism in the promoter of the serotonin transporter (5HTT; hSERT) in
      influencing susceptibility to ADHD.(3,4) Consistent with these results we have
      also found a trend for the long allele of the promoter polymorphism to influence
      susceptibility to ADHD in a sample of 113 ADHD parent proband trios (65
      transmissions vs 49 non-transmissions, chi(2) = 2.25, P = 0.13). A pooled
      analysis of our, and these published results demonstrated a significant over
      representation of the long allele of the promoter in ADHD probands compared to
      controls (chi(2) = 7.14, P = 0.008). We have also examined two other 5HTT
      polymorphisms (the VNTR in intron 2 and the 3' UTR SNP). TDT analysis
      demonstrated preferential transmission of the T allele of the 3' UTR SNP (chi(2)
      = 4.06, P = 0.04). In addition, ETDT analysis of haplotypes demonstrated
      significant preferential transmission of haplotypes containing the T allele of
      the 3' UTR SNP with the long allele of the promoter polymorphism (chi(2) = 13.18,
      3 df, P = 0.004) and the 10 repeat of the VNTR (chi(2) = 8.77, 3 df, P = 0.03).
      This study provides further evidence for the possible involvement of the
      serotonin transporter in susceptibility to ADHD.

PMID- 12232787
TI  - Synaptosomal-associated protein 25 (SNAP-25) and attention deficit hyperactivity
      disorder (ADHD): evidence of linkage and association in the Irish population.
AB  - Several lines of evidence have suggested that ADHD is a polygenic disorder
      produced by the interaction of several genes each of a minor effect. Synaptosomal
      associated protein 25 (SNAP-25) is a presynaptic plasma membrane protein which is
      expressed highly and specifically in the nerve cells. The gene encodes a protein
      essential for synaptic vesicle fusion and neurotransmitter release. Animal model
      studies showed that the coloboma mouse mutant has a hyperactive phenotype similar
      to that of ADHD. The hyperactive phenotype of this model has been shown to be the
      result of a deletion of the SNAP-25 gene. DNA variations within or closely mapped
      to the SNAP-25 gene may alter the level of expression and hence may have an
      effect on the function of synaptic vesicle fusion and neurotransmitter release.
      Using HHRR and TDT we analysed 93 ADHD nuclear families from Ireland and found
      increased preferential transmission of SNAP-25/DdeI allelel to ADHD cases; HHRR
      (chi(2) = 6.55, P = 0.01) and linkage (TDT) (chi(2) = 6.5, P = 0.015). In
      contrast to our findings, Barr et al(1) reported an increased transmission of
      allele 2 of the DdeI polymorphism though this was not statistically significant.
      However, they also reported a significantly increased transmission of a haplotype
      (made of allele 1 of MnlI and allele 2 of the DdeI) in their Canadian ADHD
      sample. It is not clear what the role of SNAP-25 in ADHD is until these findings
      are either confirmed or refuted in other ADHD samples.

PMID- 12232790
TI  - The role of mitochondrial factors in apoptosis: a Russian roulette with more than
      one bullet.
AB  - Mitochondria are 'life-essential' organelles for the production of metabolic
      energy in the form of ATP. Paradoxically mitochondria also play a key role in
      controlling the pathways that lead to cell death. This latter role of
      mitochondria is more than just a 'loss of function' resulting in an energy
      deficit but is an active process involving different mitochondrial proteins.
      Cytochrome c was the first characterised mitochondrial factor shown to be
      released from the mitochondrial intermembrane space and to be actively implicated
      in apoptotic cell death. Since then, other mitochondrial proteins, such as AIF,
      Smac/DIABLO, endonuclease G and Omi/HtrA2, were found to undergo release during
      apoptosis and have been implicated in various aspects of the cell death process.
      Members of the Bcl-2 protein family control the integrity and response of
      mitochondria to apoptotic signals. The molecular mechanism by which mitochondrial
      intermembrane space proteins are released and the regulation of mitochondrial
      homeostasis by Bcl-2 proteins is still elusive. This review summarises and
      evaluates the current knowledge concerning the complex role of released
      mitochondrial proteins in the apoptotic process.

PMID- 12232791
TI  - Cellular responses to mitochondrial dysfunction: it's not always downhill.

PMID- 12232792
TI  - Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced
      apoptosis pathway: absolute requirement for removal of caspase-6 prodomain.
AB  - Caspase activation resulting from cytochrome c release from the mitochondria is
      an essential component of the mechanism of apoptosis initiated by a range of
      factors. The activation of Bid by caspase-8 in this pathway promotes further
      cytochrome c release, thereby completing a positive feedback loop of caspase
      activation. Although the identity of the caspases necessary for caspase-8
      activation in this pathway are known, it is still unclear which protease directly
      cleaves caspase-8. In order to identify the factor responsible we undertook a
      biochemical purification of caspase-8 cleaving activity in cytosolic extracts to
      which cytochrome c had been added. Here we report that caspase-6 is the only
      soluble protease in cytochrome c activated Jurkat cell extracts that has
      significant caspase-8 cleaving activity. Furthermore the caspase-6 that we
      purified was sufficient to induce Bid dependent cytochrome c releasing activity
      in cell extracts. Inhibition of caspase-6 activity in cells significantly
      inhibited caspase-8 cleavage and apoptosis, therefore establishing caspase-6 as a
      major activator of caspase-8 in vivo and confirming that this pathway can have a
      critical role in promotion of apoptosis. We also show that caspase-6 is inactive
      until the short prodomain is removed. We suggest that the requirement for two
      distinct cleavage steps to activate an effector caspase may represent an
      effective mechanism for restriction of spontaneous caspase activation and
      aberrant entry into apoptosis.

PMID- 12232793
TI  - Programmed cell death eliminates all but one embryo in a polyembryonic plant
      seed.
AB  - Development of multiple embryos from a single zygote, the phenomenon called
      monozygotic polyembryony, is a widespread reproductive strategy found in higher
      plants and especially in gymnosperms. The enigma of plant monozygotic
      polyembryony is that only one embryo in a polyembryonic seed usually survives
      while the others are eliminated at an early stage. Here we report that programmed
      cell death (PCD) is the major mechanism responsible for elimination of
      subordinate embryos in a polyembryonic seed. Using post-fertilized pine (Pinus
      sylvestris) ovules, we show that once the dominant embryo is selected and,
      subsequently, the entire female gametophyte is affected by PCD, the cells of
      subordinate embryos initiate an autolytic self-destruction program. The
      progression of embryonic PCD follows a rigid basal-apical pattern, first killing
      the most basally situated cells, adjacent to the suspensor, and then proceeding
      towards the apical region until all cells in the embryonal mass are doomed. Our
      data demonstrate that during polyembryony, PCD serves to halt competition among
      monozygotic embryos in order to ensure survival of one embryo.

PMID- 12232795
TI  - T cell apoptosis by tryptophan catabolism.
AB  - Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that,
      expressed by different cell types, has regulatory effects on T cells resulting
      from tryptophan depletion in specific local tissue microenvironments. Different
      mechanisms, however, might contribute to IDO-dependent immune regulation. We show
      here that tryptophan metabolites in the kynurenine pathway, such as 3
      hydroxyanthranilic and quinolinic acids, will induce the selective apoptosis in
      vitro of murine thymocytes and of Th1 but not Th2 cells. T cell apoptosis was
      observed at relatively low concentrations of kynurenines, did not require Fas/Fas
      ligand interactions, and was associated with the activation of caspase-8 and the
      release of cytochrome c from mitochondria. When administered in vivo, the two
      kynurenines caused depletion of specific thymocyte subsets in a fashion
      qualitatively similar to dexamethasone. These data suggest that the selective
      deletion of T lymphocytes may be a major mechanism whereby tryptophan metabolism
      affects immunity under physiopathologic conditions.

PMID- 12232794
TI  - p53 deficiency fails to prevent increased programmed cell death in the Bcl-X(L)
      deficient nervous system.
AB  - Bcl-X(L) mice display a similar neurodevelopmental phenotype as rb, DNA ligase
      IV, and XRCC4 mutant embryos, suggesting that endogenous Bcl-X(L) expression may
      protect immature neurons from death caused by DNA damage and/or cell cycle
      dysregulation. To test this hypothesis, we generated bcl-x/p53 double mutants and
      examined neuronal cell death in vivo and in vitro. Bcl-X(L)-deficient primary
      telencephalic neuron cultures were highly susceptible to the apoptotic effects of
      cytosine arabinoside (AraC), a known genotoxic agent. In contrast, neurons
      lacking p53, or both Bcl-X(L) and p53, were markedly, and equivalently, resistant
      to AraC-induced caspase-3 activation and death in vitro indicating that Bcl-X(L)
      lies downstream of p53 in DNA damage-induced neuronal death. Despite the ability
      of p53 deficiency to protect Bcl-X(L)-deficient neurons from DNA damage-induced
      apoptosis in vitro, p53 deficiency had no effect on the increased caspase-3
      activation and neuronal cell death observed in the developing Bcl-X(L)-deficient
      nervous system. These findings suggest that Bcl-X(L) expression in the developing
      nervous system critically regulates neuronal responsiveness to an apoptotic
      stimulus other than inadequate DNA repair or cell cycle abnormalities.

PMID- 12232796
TI  - Isolation of AmphiCASP-3/7, an ancestral caspase from amphioxus (Branchiostoma
      floridae). Evolutionary considerations for vertebrate caspases.
AB  - Caspases are a large family of cysteine proteases that play an essential role as
      effectors of apoptosis in metazoans. Thirteen different caspases have been
      identified in vertebrates so far, and their function in apoptotic or inflammatory
      responses is well documented. We have taken advantage of the broadly accepted
      condition of amphioxus (Cephalochordata, Branchiostoma floridae) as the closest
      living relative to vertebrates to study the molecular evolution of caspases. Here
      we report for the first time the pattern of programmed cell death during
      development of cephalochordates. We also describe the isolation and functional
      characterisation of the first caspase related gene in amphioxus, which we named
      AmphiCASP-3/7. The amphioxus caspase is expressed throughout development, from
      the gastrula to larva stage. AmphiCASP-3/7 induced cell death when ectopically
      expressed in human HEK 293T cells, and the recombinant protein was inhibited by
      DEVD peptides. AmphiCASP-3/7 reflects the primitive condition of the executor
      vertebrates caspases -3 and -7, prior to vertebrate specific duplication.
      Interestingly, AmphiCASP-3/7 is functionally closer to vertebrate caspase-7, as
      shown by substrate specificity both in vitro and in MCF7 cells. Our phylogenetic
      and functional data help in drawing the evolutionary history of caspases, and
      illustrates an example of acquisition in vertebrates of novel functional
      properties after gene duplication.

PMID- 12232797
TI  - Osmotic stress sensitizes naturally resistant cells to TNF-alpha-induced
      apoptosis.
AB  - Most cells are naturally resistant to TNF-alpha-induced cell death and become
      sensitized when NF-kappaB transactivation is blocked or in the presence of
      protein synthesis inhibitors that prevent the expression of anti-apoptotic genes.
      In this report we analyzed the role of osmotic stress on TNF-alpha-induced cell
      death. We found that it sensitizes the naturally resistant HeLa cells to TNF
      alpha-induced apoptosis, with the involvement of an increase in the activity of
      several kinases, the inhibition of Bcl-2 expression, and a late increase on NF
      kappaB activation. Cell death occurs regardless of the enhanced NF-kappaB
      activity, whose inhibition produces an increase in apoptosis. The inhibition of
      p38 kinase, also involved in NF-kappaB activation, significantly increases the
      effect of osmotic stress on TNF-alpha-induced cell death.

PMID- 12232798
TI  - Photorepair of RNA polymerase arrest and apoptosis after ultraviolet irradiation
      in normal and XPB deficient rodent cells.
AB  - Cyclobutane pyrimidine dimers (CPDs) are directly involved in signaling for UV
      induced apoptosis in mammalian cells. Failure to remove these lesions, specially
      those located at actively expressing genes, is critical, as cells defective in
      transcription coupled repair have increased apoptotic levels. Thus, the blockage
      of RNA synthesis by lesions is an important candidate event triggering off active
      cell death. In this work, wild-type and XPB mutated Chinese hamster ovary (CHO)
      cells expressing a marsupial photolyase, that removes specifically CPDs from the
      damaged DNA, were generated, in order to investigate the importance of this
      lesion in both RNA transcription blockage and apoptotic induction. Photorepair
      strongly recovers RNA synthesis in wild-type CHO cell line, although the
      resumption of transcription is decreased in XPB deficient cells. This recovery is
      accompanied by the prevention of cells entering into apoptosis. These results
      demonstrate that marsupial photolyase has access to CPDs blocking RNA synthesis
      in vivo, and this may be affected by the presence of a mutated XPB protein.

PMID- 12232799
TI  - Caspase-12 processing and fragment translocation into nuclei of tunicamycin
      treated cells.
AB  - Excess endoplasmic reticulum (ER) stress induces processing of caspase-12, which
      is located in the ER, and cell death. However, little is known about the
      relationship between caspase-12 processing and cell death. We prepared antisera
      against putative caspase-12 cleavage sites (anti-m12D318 and anti-m12D341) and
      showed that overexpression of caspase-12 induced autoprocessing at D(318) but did
      not induce cell death. Mutation analysis confirmed that D(318) was a unique
      autoprocessing site. In contrast, tunicamycin, one of the ER stress stimuli,
      induced caspase-12 processing at the N-terminal region and the C-terminal region
      (both at D(318) and D(341)) and cell death. Anti-m12D318 and anti-m12D341
      immunoreactivities were located in the ER of the tunicamycin-treated cells, and
      some immunoreactivities were located around and in the nuclei of the apoptotic
      cells. Thus, processing at the N-terminal region may be necessary for the
      translocation of processed caspase-12 into nuclei and cell death induced by ER
      stress. Some of the caspase-12 processed at the N-terminal and C-terminal regions
      may directly participate in the apoptotic events in nuclei.

PMID- 12232801
TI  - Cell death in Leishmania induced by stress and differentiation: programmed cell
      death or necrosis?
AB  - Unicellular organisms, such as the protozoan parasite Leishmania, can be
      stimulated to show some morphological and biochemical features characteristic of
      mammalian apoptosis. This study demonstrates that under a variety of stress
      conditions such as serum deprivation, heat shock and nitric oxide, cell death can
      be induced leading to genomic DNA fragmentation into oligonucleosomes. DNA
      fragmentation was observed, without induction, in the infectious stages of the
      parasite, and correlated with the presence of internucleosomal nuclease activity,
      visualisation of 45 to 59 kDa nucleases and detection of TUNEL-positive nuclei.
      DNA fragmentation was not dependent on active effector downstream caspases nor on
      the lysosomal cathepsin L-like enzymes CPA and CPB. These data are consistent
      with the presence of a caspase-independent cell death mechanism in Leishmania,
      induced by stress and differentiation that differs significantly from metazoa.

PMID- 12232800
TI  - Distinct downstream pathways of caspase-11 in regulating apoptosis and cytokine
      maturation during septic shock response.
AB  - Caspase-11 is an essential mediator of septic shock response and caspase-11
      deficient mice are resistant to LPS-induced shock. Here we report that LPS
      induced caspase-11 regulates lymphocyte apoptosis by activating both caspase-3
      and caspase-7. The activation of caspase-11 preceded that of caspase-1 and
      caspases-3/-7, and in the absence of caspase-11, the activation of caspases-3/-7
      was significantly reduced. The early activation of caspases-3/-7 by caspase-11
      was not affected by blocking of caspase-1 activity and IL-1beta release, implying
      that caspase-11 activates caspases-3/-7 independently of caspase-1 activation.
      Furthermore, we show that caspase-11-mediated apoptosis under septic condition is
      Bid-independent. Our work suggests that the human homologue of caspase-11 may be
      an effective therapeutic target for treatment of septic shock.

PMID- 12232802
TI  - The C-terminal activation domain of the STAT-1 transcription factor is necessary
      and sufficient for stress-induced apoptosis.
AB  - It has previously been demonstrated that the STAT-1 transcription factor plays a
      key role in apoptosis induced by the cellular regulatory factors interferon gamma
      and TNF-alpha. Here we demonstrate that cells lacking STAT-1 show reduced cell
      death/apoptosis in response to stressful stimuli such as heat or ischaemia.
      Expression of STAT-1 in these cells does not enhance basal cell death but
      restores sensitivity to stress-induced death whereas this effect is not observed
      upon over-expression of STAT-3. Enhanced sensitivity to stress-induced cell death
      requires the C-terminal activation domain of STAT-1 and the phosphorylation sites
      at tyrosine 701 and serine 727. Moreover, we show for the first time in any
      system that the isolated C-terminal domain of STAT-1 is able to enhance stress
      induced cell death in the absence of the DNA binding domain or any other region
      of STAT-1. Hence, STAT-1 plays a key role in stress-induced cell death,
      potentially acting via a novel co-activator-type mechanism and represents a
      possible therapeutic target for strategies aimed at minimising cell death, for
      example, following ischaemic injury.

PMID- 12232804
TI  - Calabria: sun, sand, and cell death.

PMID- 12232805
TI  - Superoxide and nitric oxide--participation in cell communication.

PMID- 12232803
TI  - Decreased glycolytic metabolism contributes to but is not the inducer of
      apoptosis following IL-3-starvation.
AB  - IL-3 regulates the glycolytic pathway. In Baf-3 cells IL-3 starvation leads to a
      decrease in glucose uptake and in lactate production. To determine if there is a
      link between the decreased metabolism induced by growth factor-starvation and the
      induction of cell death, we have compared the cell death characteristics and the
      metabolic modifications induced by IL-3-deprivation or glucose-deprivation in Baf
      3 cells. We show that in both conditions cells die by an apoptotic process which
      involves the activation of similar Caspases. Different metabolic parameters (i.e.
      intracellular ATP levels and lactate accumulation in the culture medium) were
      measured. We show that IL-3 deprivation leads to a partial decrease in lactate
      production in contrast to glucose deprivation that completely inhibits lactate
      production. Similarly following IL-3-starvation a significant drop in the
      intracellular ATP levels in live cells is observed only after 16 h when a large
      fraction, more than 50 per cent of cells, is already apoptotic. On the contrary,
      glucose deprivation is followed by an abrupt decrease in ATP levels in the first
      2 h of treatment. However, in the presence of IL-3, cells are able to survive for
      an extended time in these conditions since 70% of cells survived with low ATP
      levels for up to 16 h. This was not due to partial inhibition of the apoptotic
      process by the low level of ATP as glucose-deprivation in the absence of IL-3 led
      to faster death kinetics of Baf-3 cells compared with IL-3 starvation only. These
      results indicate that the drop in ATP levels and the triggering of apoptosis can
      be dissociated in time and that when the glycolytic pathway is strongly
      inhibited, cells are able to survive with relatively low ATP levels if IL-3 is
      present. Finally we show that induction of bcl-x by IL-3 protects cells from
      glucose-deprivation induced cell death.

PMID- 12232806
TI  - [Editorial].

PMID- 12232807
TI  - [The incompetent expert--Possible measures against incompetent expertising].

PMID- 12232808
TI  - [Psychological aspects of lifestyle and prevention].

PMID- 12232809
TI  - [Prevention and lifestyle in gynaecology and obstetrics: a review].

PMID- 12232810
TI  - [Prevention with phyto-oestrogens].

PMID- 12232811
TI  - [Possibilities of preventing carcinomas of the breast].

PMID- 12232812
TI  - [New trends in the conservative and surgical treatment of endometriosis].

PMID- 12232813
TI  - [Evidence-based recommendations on treating locoregional and distant metastases
      of carcinomas of the breast].

PMID- 12232814
TI  - [Evidence-based recommendations on primary treatment of carcinomas of the
      breast].

PMID- 12232815
TI  - [Expression of the molecules HLA-G and HLA-E modulates cytokine production of
      monocyte generated dendritic cells].
AB  - OBJECTIVE: Preferential secretion of Th1-like cytokine is mainly a property of
      monocyte derived dendritic cells (DC). Since normal early pregnancy is
      characterized by a shift towards a Th2-like cytokine pattern, it may be assumed
      that cytokine secretion by DC during early pregnancy could be modulated by the
      non-classical HLA molecules G and E present on invasive trophoblast. MATERIAL AND
      METHODS: DC were cultivated from monocytes isolated from peripheral blood
      mononuclear cells. DC were cocultured with K-562 leukemia cells lacking the class
      I and II HLA antigens transfected with either HLA-G or HLA-E or ultratransfected
      cells (controls) and the concentrations of IL-8, IL-10, IL-12p70, IL-18 and TNF
      alpha were measured in the supernatants by ELISA. RESULTS: Coculture with
      ultratransfected cells resulted in a significant increase of the production of IL
      8 and TNF-alpha by mature and immature DC and of IL-10 by immature DC (p < 0.01).
      When cocultured with HLA-G and HLA-E transfected K-562 cells, the secretion of IL
      8 by immature and mature DC and that of IL-10 and TNF-alpha by immature DC was
      significantly (p < 0.01) decreased. The contact with HLA-G and HLA-E transfected
      cells had no effect on the production of IL-12p70 and IL-18 by DC. CONCLUSIONS:
      These results show that DC react with an increased cytokine release upon contact
      with cells lacking HLA class I and II antigens. The suppressive effect of HLA-G
      and HLA-E on the secretion of TNF-alpha (Th1 cytokine), IL-10 (Th2 cytokine) and
      IL-8 (chemokine) by immature DC could be interpreted as further evidence for the
      central immunotolerance role of HLA-G and HLA-E during early pregnancy.

PMID- 12232817
TI  - State of the art--a journey through the world of antithrombotic therapy.
AB  - The introduction of low-molecular-weight heparins (LMWHs) has contributed to
      major improvements in the management of venous thromboembolism (VTE). The LMWHs
      have been shown to be as effective as, and safer than, unfractionated heparin
      (UFH) in the prevention and treatment of VTE, and their use is included as a
      grade 1A recommendation in the Sixth American College of Chest Physicians
      Guidelines. Important practical disadvantages of treatment with UFH are the need
      for extended hospital stays and frequent monitoring of coagulation levels. In
      comparison, LMWHs offer convenient and cost-effective prophylaxis and treatment
      of VTE on an outpatient basis. The LMWHs have also had a major impact on the
      management of arterial thromboembolism. In patients with acute coronary syndromes
      (unstable angina and non-ST-segment elevation myocardial infarction), enoxaparin
      has demonstrated sustained clinical improvements in major ischemic outcomes
      compared with UFH. Antiplatelet agents have also contributed significantly to the
      development of effective antithrombotic therapy. Aspirin is the best known
      antiplatelet agent and has heretofore been the mainstay of antiplatelet therapy
      in unstable angina. New data indicate that combination therapy with aspirin and a
      novel thienopyridine, clopidogrel, may further improve outcomes in this
      indication.

PMID- 12232818
TI  - Discoveries in thrombosis care for medical patients.
AB  - Medical patients represent the majority of hospitalized patients, and at least
      75% of fatal pulmonary emboli occur in this group. Medical patients are at
      significant risk of thromboembolic disease, yet few are considered for
      thromboprophylaxis. Recent studies have identified the risk factor profiles in
      this group of patients, and a risk assessment model for medical patients has been
      developed. Risk stratification will help to ensure that patients receive
      appropriate thromboprophylaxis. It is clear that patients with severe chronic
      respiratory disease, congestive heart failure, and infectious disease are at high
      risk of symptomatic venous thromboembolism (VTE), particularly pulmonary
      embolism. Heparin-based prophylaxis significantly reduces the incidence of VTE.
      Low-molecular-weight heparin offers a safe and cost-effective alternative to
      unfractionated heparin in medical patients; to date, enoxaparin is the only low
      molecular-weight heparin licensed for thromboprophylaxis in this indication.

PMID- 12232819
TI  - Venous thromboembolism in cancer patients: expanding horizons.
AB  - Venous thromboembolism (VTE) and particularly idiopathic VTE may be
      paraneoplastic phenomena. The merits of screening patients with idiopathic VTE
      for occult cancer are still under debate, and randomized studies are required to
      establish its potential cost-effectiveness. Cancer and its related surgery
      greatly increase the risk of VTE. Thromboprophylaxis using agents such as low
      molecular-weight heparin (LMWH) has proved to be safe and effective in reducing
      the incidence of postoperative VTE. The ENOXACAN II study has shown that
      prolonging the standard 1-week regimen of the LMWH enoxaparin to 4 weeks may
      further reduce the incidence of postoperative VTE. Enoxaparin has also shown
      potential benefits in the secondary prevention of VTE and the reduction of
      bleeding complications. Emerging data indicate that LMWH may improve survival
      rates in cancer patients with VTE, making this a very important area for future
      research.

PMID- 12232820
TI  - Exploring the role of low-molecular-weight heparins in pregnancy.
AB  - Thromboembolic complications are leading causes of both maternal and fetal
      morbidity and mortality. To reduce the incidence of venous thromboembolism (VTE)
      in pregnancy and improve outcomes, a wider understanding of the risk factors
      involved and better identification of women at risk of thrombosis are required.
      Optimal management of thromboembolic disease, both to prevent VTE and to avoid
      recurrence of pregnancy complications such as miscarriage, centers on the use of
      low-molecular-weight heparin (LMWH). LMWHs, such as enoxaparin and dalteparin,
      have clinical and practical advantages compared with unfractionated heparin in
      terms of improved safety (significantly lower incidence of osteoporosis,
      thrombocytopenia, and possibly allergic skin reactions) and the potential for
      outpatient treatment of acute VTE. However, many unanswered questions remain,
      including who to treat, how to treat them, and when to treat in the case of
      patients with thrombophilia and a history of previous pregnancy complications.

PMID- 12232822
TI  - Introduction--venous thromboembolism management in the real world: your
      opportunity to participate in a critical assessment.

PMID- 12232821
TI  - Mapping out the future in venous thromboembolism and acute coronary syndromes.
AB  - Identification of risk factors for incident venous thromboembolism and predictors
      of recurrent venous thromboembolism and appropriate antithrombotic prophylaxis
      and therapy are vital to improve survival after pulmonary embolism and prevent
      complications such as venous stasis syndrome after deep-vein thrombosis. Risk
      stratification is increasingly important; future prophylaxis and treatment
      strategies should be targeted to the patients who will derive the greatest
      benefit. For established antithrombotic agents, the most appropriate dose, dosing
      schedule, and duration of prophylaxis and therapy are being refined. In addition,
      new antithrombotic agents such as the oral direct thrombin inhibitors are being
      identified and developed. The management of acute arterial thrombosis (for
      example, acute coronary syndromes) is an important and relatively new indication
      for antithrombotic agents such as the low-molecular-weight heparins and the
      platelet glycoprotein IIb/IIIa antagonists.

PMID- 12232823
TI  - Prolonged prophylaxis in orthopedic surgery: insights from the United States.
AB  - The U.S. Hip and Knee Registry is a voluntary national registry of outcome data
      for hip and knee surgery. In total, 469 orthopedic surgeons from 325 hospitals
      reported data on 7677 patients who underwent total hip arthroplasty (THA) and
      11,461 patients who underwent total knee arthroplasty (TKA). Data on patients
      enrolled between 1996 and 2000 indicate that 40% of THA patients and 42% of TKA
      patients received prophylaxis for a period of 8 to 21 days, including the in
      hospital period. Prolonged prophylaxis for more than 21 days was used in 49% of
      THA patients and 44% of TKA patients. Moreover, year on year, data indicate that
      the percentage of patients who receive prophylaxis for longer than 21 days is
      gradually increasing. In 2000, 53% of THA patients and 47% of TKA patients
      received prophylaxis for longer than 21 days.

PMID- 12232824
TI  - Managing venous thromboembolism in Latin American patients: emerging results from
      the Brazilian Registry.
AB  - A Brazilian National Registry was established in 1999 to investigate the
      incidence of risk factors for venous thromboembolism (VTE) in hospitalized
      medical and surgical patients and to investigate the use of thromboprophylaxis in
      these populations. A 4-year pilot study confirmed the feasibility and value of a
      registry project in this region, showing a dramatic increase in the use of low
      molecular-weight heparin (LMWH) over the study period, associated with a sixfold
      reduction in the incidence of symptomatic VTE. Data on more than 27,000 patients
      from the Brazilian Registry have revealed that almost 25% of high-risk patients
      and 45% of those at moderate risk currently receive no thromboprophylaxis. Among
      the high-risk patients-in whom general measures alone are not considered
      appropriate prophylaxis-42% of patients did not receive pharmacological
      prophylaxis with either LMWH or unfractionated heparin. The Brazilian Registry
      highlights the need to raise awareness of VTE risk factors and recommended
      prophylactic regimens in Latin America.

PMID- 12232825
TI  - Thromboprophylaxis in medical patients: focus on France.
AB  - In 2000, the French authorities licensed the low-molecular-weight heparin (LMWH)
      enoxaparin for thromboprophylaxis in acutely ill medical patients. However, the
      lack of official recommendations for this group of patients has contributed to
      inappropriate use of LMWH. The recent College of Internal Medicine of Paris
      (CIMOP) and Donnees Epidemiologiques chez les Patients A Risque Thromboembolique
      (DEPART) epidemiological studies have confirmed that LMWH is prescribed for 32%
      of medical inpatients and up to 44% of outpatients. However, they highlight
      overuse in elderly bedridden patients without acute illness and underuse in
      patients with severe infections or cardiopulmonary disease. Guidelines are
      urgently needed to encourage French physicians to target thromboprophylaxis for
      medical patients who are genuinely at high risk of thromboembolic disease and to
      prescribe the appropriate dose and duration of therapy.

PMID- 12232827
TI  - Differential regulation of interleukin (IL)-4, IL-5, and IL-10 during measles in
      Zambian children.
AB  - To determine the effect of measles virus infection on cytokine production in
      children from sub-Saharan Africa, temporal changes in cytokine production in vivo
      were analyzed and the T cell sources of type 1 and type 2 cytokines were
      identified in Zambian children with measles. The immune response during measles
      involved early type 1 responses, with production of interferon-gamma by CD8(+) T
      cells and of interleukin (IL)-2 by CD4(+) T cells. Subsequently, more-prolonged
      increases were observed in the type 2 cytokines IL-4 and IL-13, both produced by
      CD4(+) T cells. IL-5 was regulated differently from IL-4 and IL-13: levels were
      low compared with levels in control children and were reflected in lower
      eosinophil counts during measles. Immunoglobulin E was lower in children with
      measles, despite high levels of IL-4 and IL-13. Plasma levels of IL-10 were
      elevated for weeks, potentially contributing to impaired cellular immunity and
      depressed hypersensitivity responses following measles.

PMID- 12232828
TI  - The molecular epidemiology of varicella-zoster virus: evidence for geographic
      segregation.
AB  - Of 75 varicella-zoster virus (VZV) isolates obtained from patients in Africa,
      Asia, and the Far East, 74 (98.6%) were found to be positive for a BglI
      restriction site in gene 54. By contrast, <22% of strains from patients in the
      United Kingdom and in North and South America were positive for the BglI
      restriction site. Viruses positive for BglI were significantly more common in
      zoster occurring in patients of nonwhite origin (P<.05). Irrespective of the
      country in which the sample was obtained, 98% of strains positive for BglI
      clustered within a single phylogenetic group, which we termed "group A"; the
      exception was 1 strain that appeared to be recombinant genotype C/A. We used the
      BglI site to examine both the spread of type A viruses in the United Kingdom and
      the patterns of VZV infections within persons from different ethnic groups who
      grew up in the United Kingdom or abroad.

PMID- 12232829
TI  - Fetal feline immunodeficiency virus is prevalent and occult.
AB  - The feline model of human acquired immune deficiency syndrome, feline
      immunodeficiency virus (FIV), was used to model maternal-to-fetal human
      immunodeficiency virus type 1 (HIV-1) transmission. Fetuses were collected from
      cats infected with clade A FIV(Petaluma) (FIV-A-Pet) and clade C FIV(PaddyGammer)
      (FIV-C-Pgmr). Virus was detected by DNA polymerase chain reaction (PCR) and a
      quantitative RNA assay that used substitutional PCR. FIV in tissue sections was
      assayed by DNA and RNA in situ hybridization and immunohistochemistry. Viral DNA
      was detected in 67% and 92% of fetuses with FIV-A-Pet and FIV-C-Pgmr,
      respectively. A discordance was observed between placental and fetal FIV-A-Pet
      localization. FIV sequestration in fetal tissues was common without detectable
      virus in blood (occult infection). Viral RNA was not detected in amniotic fluid
      or fetal plasma. In situ assays demonstrated FIV DNA but neither RNA nor antigens
      in placentas and fetuses. If mother-to-offspring FIV infection reflects vertical
      HIV-1 transmission, fetal virus exposure is common and may be occult at term.

PMID- 12232830
TI  - The central nervous system as a reservoir for simian immunodeficiency virus
      (SIV): steady-state levels of SIV DNA in brain from acute through asymptomatic
      infection.
AB  - Latent reservoirs of human immunodeficiency virus (HIV) present significant
      challenges for eradicating HIV from infected persons, particularly reservoirs in
      the brain established during acute infection. A simian immunodeficiency virus
      (SIV)/macaque model of HIV dementia was used to show that viral DNA levels in the
      brain remained at constant levels from acute through asymptomatic infection,
      despite significant down-regulation of viral RNA in the brain after the acute
      phase of infection. Viral replication in the brain coincided with activation of
      macrophages and microglia in the central nervous system; down-regulation of viral
      replication coincided with increased infiltration of cytotoxic lymphocytes and
      reduced activation of macrophages and microglia in the brain. Comparison of viral
      genotypes in the central nervous system and peripheral blood mononuclear cells
      suggests that recrudescence of viral replication in brain occurs by reactivation
      of latent viral DNA. Latent virus in the brain must be considered in therapeutic
      strategies to eliminate HIV from infected persons.

PMID- 12232831
TI  - Link between the X4 phenotype in human immunodeficiency virus type 1-infected
      mothers and their children, despite the early presence of R5 in the child.
AB  - Coreceptor use was determined for human immunodeficiency virus type 1 (HIV-1)
      isolates of various subtypes from 11 women during pregnancy and their infected
      children. Isolates from peripheral blood mononuclear cells (n=79) and from plasma
      (n=59) were available. The clinical and immunological stages of HIV-1 infection
      were recorded. Coreceptor use was tested on human cell lines expressing CD4 and
      different chemokine receptors. The R5 virus predominated, and only 9 isolates
      from 2 mothers used CXC chemokine receptor 4. All children carried the R5 virus
      at the time of diagnosis of HIV-1 infection. In 2 children of mothers carrying
      the X4 virus, the virus switched from R5 to X4 or to R5X4 by age 18 months (child
      no. 9) and age 48 months (child no. 10), whereas no children followed up to a
      similar age whose mothers were carrying the R5 virus experienced such a switch
      (P=.048). This points to a link between the presence of X4 virus in the mother
      and the emergence of X4 virus in her child.

PMID- 12232832
TI  - Plasma stromal cell-derived factor (SDF)-1 levels, SDF1-3'A genotype, and
      expression of CXCR4 on T lymphocytes: their impact on resistance to human
      immunodeficiency virus type 1 infection and its progression.
AB  - Plasma stromal cell-derived factor (SDF)-1 levels, SDF1-3'A polymorphism, and
      CXCR4(+) T lymphocytes in relation to resistance to human immunodeficiency virus
      (HIV)-1 infection and its progression were investigated in a study of HIV
      positive patients, exposed but uninfected (EU) subjects, and healthy control
      subjects, all lacking CCR5 Delta 32 homozygosity. SDF1-3'A homozygosity was
      associated with low plasma SDF-1 levels in uninfected persons and was not related
      to long-term nonprogression. HIV-1 infection involved increased plasma SDF-1
      levels, which were not attributable to any kind of chronic viral infection,
      because all EU hemophiliacs were hepatitis C virus-positive but had normal SDF-1
      levels. High plasma SDF-1 levels and low CXCR4 expression on T lymphocytes was
      associated with long-term nonprogression, whereas in advancing disease expression
      of CXCR4 increased, accompanied by a decrease in plasma SDF-1 during the more
      advanced stages of HIV-1 infection. EU subjects with sexual exposure to HIV-1,
      but not EU hemophiliacs, showed an underpresentation of SDF1-3'A allele
      frequency, which was coupled with high plasma SDF-1 levels and low CXCR4
      expression.

PMID- 12232833
TI  - Polygenic control of human T lymphotropic virus type I (HTLV-I) provirus load and
      the risk of HTLV-I-associated myelopathy/tropical spastic paraparesis.
AB  - Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) is one outcome of infection with HTLV-I. A population
      association study of 229 patients with HAM/TSP and 202 healthy carriers of HTLV-I
      in southern Japan showed that this outcome of HTLV-I infection and the HTLV-I
      provirus load are under polygenic control. Of 58 polymorphic sites studied in 39
      non-HLA candidate gene loci, 3 new host genetic factors that influenced the risk
      of HAM/TSP or the provirus load of HTLV-I were identified. The promoter TNF -863A
      allele predisposed to HAM/TSP, whereas SDF-1 +801A 3'UTR, and IL-15 191C alleles
      conferred protection. Knowledge of HTLV-I-infected individuals' ages, sex,
      provirus load, HTLV-I subgroup, and genotypes at the loci HLA-A, HLA-C, SDF-1,
      and TNF-alpha allowed for the correct identification of 88% of cases of HAM/TSP
      in this Japanese cohort.

PMID- 12232834
TI  - Syphilis in pregnancy in Tanzania. I. Impact of maternal syphilis on outcome of
      pregnancy.
AB  - To measure the impact of maternal syphilis on pregnancy outcome in the Mwanza
      Region of Tanzania, 380 previously unscreened pregnant women were recruited into
      a retrospective cohort at delivery and tested for syphilis. Stillbirth was
      observed in 18 (25%) of 73 women with high-titer active syphilis (i.e., women
      with a rapid plasma reagin titer > or = 1 :8 and a positive Treponema pallidum
      hemagglutination assay or indirect fluorescent treponemal antibody test result),
      compared with 3 (1%) of 233 uninfected women (risk ratio [RR], 18.1; P<.001).
      Women with high-titer active syphilis were also at the greatest risk of having
      low-birth-weight or preterm live births (RR, 3.0 and 6.1, respectively), compared
      with women with other serological stages of syphilis. Among unscreened women, 51%
      of stillbirths, 24% of preterm live births, and 17% of all adverse pregnancy
      outcomes were attributable to maternal syphilis. Syphilis continues to be a major
      cause of pregnancy loss and adverse pregnancy outcome among women who do not
      receive antenatal syphilis screening and treatment.

PMID- 12232835
TI  - Syphilis in pregnancy in Tanzania. II. The effectiveness of antenatal syphilis
      screening and single-dose benzathine penicillin treatment for the prevention of
      adverse pregnancy outcomes.
AB  - Treatment for maternal syphilis with single-dose benzathine penicillin (2.4
      million units intramuscularly) is being implemented in many parts of sub-Saharan
      Africa. To examine the effectiveness of this regimen, a prospective cohort of
      1688 pregnant women was recruited in Tanzania. Birth outcomes were compared among
      women treated for high-titer (n=133; rapid plasma reagin [RPR] titer > or = 1:8
      and Treponema pallidum hemagglutination assay [TPHA]/fluorescent treponemal
      antibody [FTA] positive) and low-titer (n=249; RPR titer <1:8 and TPHA/FTA
      positive) active syphilis and 950 uninfected women. Stillbirth or low-birth
      weight live births were observed in 2.3% and 6.3%, respectively, of women treated
      for high-titer active syphilis and in 2.5% and 9.2%, respectively, of
      seronegative women. There was no increased risk for adverse pregnancy outcome for
      women treated for high-titer active syphilis (odds ratio [OR], 0.76; 95%
      confidence interval [CI], 0.4-1.4) or low-titer active syphilis (OR, 0.95; 95%
      CI, 0.6-1.5), compared with seronegative women. Single-dose treatment is
      effective in preventing adverse pregnancy outcomes attributable to maternal
      syphilis.

PMID- 12232836
TI  - Reemergence, in southwestern Alaska, of invasive Haemophilus influenzae type b
      disease due to strains indistinguishable from those isolated from vaccinated
      children.
AB  - Haemophilus influenzae type b (Hib) invasive disease and oropharyngeal carriage
      continue in rural Alaska despite widespread vaccination. This study investigated
      whether invasive-disease reemergence during 1996-1997 could be attributed to
      strains distinguishable from strains carried by vaccinated children. Twenty-four
      invasive and 42 carriage Hib isolates, collected during 1992-1997, were
      characterized by pulsed-field gel electrophoresis (PFGE), multilocus enzyme
      electrophoresis, and biotyping. This Hib population was highly clonal, since only
      2 strains, electrophoretic type (ET) 55/PFGE 1 and ET 56/PFGE 3, accounted for
      62% of all isolates. The ET 55/PFGE 1 and ET 56/PFGE 3 strains were found in 74%
      of the carriers and caused 80% of the invasive Hib disease that occurred during
      April 1996-March 1997. Strains causing invasive disease could not be
      distinguished from strains carried by vaccinated children. Continued monitoring
      of Hib carriage may provide insights into the epidemiology of continued
      transmission in an era of widespread vaccination.

PMID- 12232837
TI  - Diversity of penicillin-nonsusceptible Streptococcus pneumoniae circulating in
      Iceland after the introduction of penicillin-resistant clone Spain(6B)-2.
AB  - After the introduction and extensive dissemination of the multidrug-resistant
      Streptococcus pneumoniae clone Spain(6B)-2 between 1989 and the early to mid
      1990s, the prevalence of pneumococcal isolates expressing intermediate resistance
      to penicillin, mainly of capsular types 6, 19, and 23, also began to increase in
      Iceland. The purpose of this study was to investigate whether these isolates
      originated in Iceland or represented strains imported to the country. Isolates
      were characterized by pulsed-field gel electrophoresis; multilocus sequence
      typing; determination of pbp1a, pbp2b, and pbp2x gene restriction patterns; and
      partial sequencing of these pbp genes. The results indicate that, although
      singular events suggesting horizontal transfer of pbp genes (and capsular genes)
      were detected, the majority of clones circulating in the country had genetic
      backgrounds also detected abroad. The major mechanism of dissemination of
      penicillin resistance in Iceland appears to be the repeated introduction of
      multiple lineages, followed by clonal spread.

PMID- 12232838
TI  - Molecular basis for up-regulation by inflammatory cytokines of Shiga toxin 1
      cytotoxicity and globotriaosylceramide expression.
AB  - Mortality in postdiarrheal hemolytic-uremic syndrome (HUS) is associated with
      brain injury. Normally, brain cells are resistant to Shiga toxin (Stx), the
      putative pathogenic toxin in HUS. However, exposure of human brain endothelial
      cells (HBECs) to tumor necrosis factor (TNF) and/or interleukin (IL)-1 markedly
      up-regulates Stx receptor (globotriaosylceramide; Gb3) expression and
      cytotoxicity. To investigate how Gb3 is augmented, ceramide glucosyltransferase
      (CGT), lactosylceramide synthase (GalT2), Gb3 synthase (GalT6), and alpha
      galactosidase were studied in HBECs exposed to TNF and IL-1. TNF, both alone and
      in combination with IL-1, increased Stx-1 toxicity, Gb3 content, and Stx-1
      binding. TNF in combination with IL-1 increased CGT, GalT2, and GalT6 but did not
      change alpha-galactosidase activities or mRNA levels. Cytokine treatment did not
      change CGT, GalT2, or GalT6 mRNA half-lives. Thus, inflammatory cytokine up
      regulation of the sensitivity of HBECs to Stx-1 is the result of up-regulation,
      most likely via transcription, of the activities of 3 enzymes involved in Gb3
      synthesis.

PMID- 12232839
TI  - Epidemiology of endemic Bartonella bacilliformis: a prospective cohort study in a
      Peruvian mountain valley community.
AB  - Bartonella bacilliformis has caused debilitating illness since pre-Incan times,
      but relatively little is known about its epidemiology. A population-based,
      prospective cohort investigation was conducted in a Peruvian community with
      endemic bartonellosis. By use of house-to-house and hospital surveillance
      methods, cohort participants were monitored for evidence of bartonellosis. Of 690
      participants, 0.5% had asymptomatic bacteremia at study initiation. After 2 years
      of follow-up, the incidence of infection was 12.7/100 person-years. The highest
      rates were in children <5 years old, and there was a linear decrease in incidence
      with increasing age. Seventy percent of cases were clustered in 18% of
      households. Age and bartonellosis in a family member were the best predictors of
      B. bacilliformis infection. There were multiple clinical presentations and
      significant subclinical infection. A cost-effective control strategy should
      include vector control and surveillance efforts focused on children and clusters
      of households with highest endemicity.

PMID- 12232840
TI  - Identification of epitopes of Mycobacterium tuberculosis 16-kDa protein
      recognized by human leukocyte antigen-A*0201 CD8(+) T lymphocytes.
AB  - CD8(+) T cells could make an important contribution to protection against
      tuberculosis (TB), but the antigenic determinants recognized in the context of
      major histocompatibility complex class I molecules remain ill defined. Our aim
      was to identify nonamer peptides derived from the acr/16-kDa antigen. Two
      immunogenic peptides (p21-29 and p120-128) were identified by their ability to
      elicit cytotoxic CD8(+) T cells from juvenile patients recovering from TB.
      Epitope-specific recognition was demonstrated by the lysis of both Mycobacterium
      tuberculosis-infected and peptide-pulsed macrophages, the release of cytotoxic
      granules, and interferon-gamma and tumor necrosis factor-alpha production. CD8(+)
      T cell responses to p21-29 and p120-128 were detected ex vivo in freshly isolated
      peripheral blood mononuclear cells from patients with TB but not in those from
      healthy control subjects. Our data suggest that these antigenic peptides can play
      a critical role in effective immunity against mycobacterial infection and TB.

PMID- 12232841
TI  - Origin and dissemination of Plasmodium falciparum drug-resistance mutations in
      South America.
AB  - Multidrug resistance is a major obstacle to the control of Plasmodium falciparum
      malaria, and its origins and modes of dissemination are imperfectly understood.
      In this study, haplotyping and microsatellite analysis of malaria from 5 regions
      of the South American Amazon support the conclusion that the parasite mutations
      conferring mid- and high-level resistance to the antifolate combination
      sulfadoxine-pyrimethamine have a common origin. Parasites harboring these
      mutations are also found to share drug-resistance alleles that confer a unique
      chloroquine resistance phenotype and to be similar at loci not linked to drug
      resistance, although not genetically identical. Since the 1980s, multidrug
      resistant P. falciparum has spread in a north-northwest manner across the
      continent, from an origin likely in the lower Amazon. This study highlights the
      importance of continent-wide malaria-control policies and suggests that the
      containment of resistance to the next generation of therapies may be feasible.

PMID- 12232842
TI  - Profound bias in interferon-gamma and interleukin-6 allele frequencies in western
      Kenya, where severe malarial anemia is common in children.
AB  - The intensity of malaria transmission is related to the pattern of malarial
      disease observed in different regions, but populations may also differ in their
      underlying predispositions to severe malarial anemia or cerebral malaria. In
      western Kenya, where severe malarial anemia is much more common than cerebral
      malaria, the distributions of tumor necrosis factor (TNF)-alpha, interleukin (IL)
      10, transforming growth factor (TGF)-beta, IL-6, and interferon (IFN)-gamma
      alleles were examined in a cohort of young men. The cohort displayed a marked
      bias toward genotypes associated with low expression of IFN-gamma and IL-6,
      cytokines that, at high levels, have been implicated in malarial anemia and poor
      malaria outcomes. By contrast, the frequency of the TNF-alpha -238A allele, which
      has been associated with severe malarial anemia, was found to be similar to the
      frequency previously reported in comparison populations in Africa and elsewhere.
      IFN-gamma and IL-6 genotypes may play roles in the development of severe malaria
      and could contribute to the relative frequency of severe malarial anemia or
      cerebral malaria in exposed populations.

PMID- 12232843
TI  - Influence of filgrastim (granulocyte colony-stimulating factor) on human
      immunodeficiency virus type 1 RNA in patients with cytomegalovirus retinitis.
AB  - Filgrastim, or granulocyte colony-stimulating factor, reverses neutropenia
      associated with human immunodeficiency virus type 1 (HIV-1) and cytomegalovirus
      (CMV) infections. During a trial of anti-CMV retinitis therapies coadministered
      with antiretroviral therapy, 2-4 plasma specimens of HIV-1 RNA were collected
      from 36 HIV-1-infected patients receiving filgrastim to prevent neutropenia and
      from 36 patients not receiving filgrastim. For both groups, the crude mean and
      mean rate of change of HIV-1 log(10) RNA levels were similar. Adjustment for
      covariates (CD4(+) T cell lymphocytes, virus load at enrollment, level of
      neutropenia and antiretroviral therapy [mainly non-highly active antiretroviral
      therapy], and anti-CMV therapy during follow-up) resulted in a mean log(10) HIV-1
      RNA level for individuals receiving filgrastim versus those not receiving the
      drug of 5.11 versus 4.87 (P=.12) and respective log mean rates of change per
      month of -0.08 versus -0.21 (P=.08). This latter difference has borderline
      statistical significance, which suggests that filgrastim may reduce the decline
      of HIV-1 RNA loads.

PMID- 12232844
TI  - Characterization of sexually transmitted disease clinic patients with recent
      human immunodeficiency virus infection.
AB  - The serologic testing algorithm for recent human immunodeficiency virus (HIV)
      seroconversion (STARHS) distinguishes between recent acquisition of HIV infection
      (seroconversion, on average, in the past 129 days) or long-standing infection.
      STARHS was offered to sexually transmitted disease clinic patients to estimate
      HIV incidence and determine correlates of recent infection from October 1998
      through December 1999. Of the 5227 patients tested, 116 (2.1%) were HIV infected,
      and 28 had recent infections. The incidence was highest among homosexual men
      (5.3%/year; 95% confidence interval [CI], 2.6%-10.0%), those who had HIV-infected
      partners (8.6%/year; 95% CI, 2.9%-21.1%), and those who had gonorrhea (6.7%/year;
      95% CI, 1.5%-20.3%). Among homosexual men, African American (odds ratio [OR],
      3.61; 95% CI, 1.13-11.55) or Latino (OR, 3.08; 95% CI, 1.11-8.55) race/ethnicity,
      and having unprotected anal intercourse (OR, 2.98; 95% CL, 1.20-7.45) or
      gonorrhea (OR, 3.03 95% CI, 1.07-8.63) predicted the predominance of a recent
      seroconversion. HIV infections in San Francisco may be shifting from white men
      who have sex with men to men of color who have sex with men.

PMID- 12232845
TI  - Trends in causes of death among persons with acquired immunodeficiency syndrome
      in the era of highly active antiretroviral therapy, San Francisco, 1994-1998.
AB  - To understand recent temporal trends in acquired immunodeficiency syndrome (AIDS)
      mortality in the era of highly active antiretroviral therapy (HAART), trends in
      causes of death among persons with AIDS in San Francisco who died between 1994
      and 1998 were analyzed. Among 5234 deaths, the mortality rate for human
      immunodeficiency virus (HIV)-related or AIDS-related deaths declined after 1995
      (P<.01), whereas the mortality rate for non-HIV- or non-AIDS-related deaths
      remained stable. The proportion of deaths of persons with AIDS associated with
      septicemia, non-AIDS-defining malignancy, chronic liver disease, viral hepatitis,
      overdose, obstructive lung disease, coronary artery disease, and pancreatitis
      increased (P<.05). The standardized mortality ratio was high for these causes in
      both pre- and post-HAART periods, except for pancreatitis, a possible
      complication of HAART, which demonstrated an increasing standardized mortality
      ratio trend after 1996. With increasing AIDS survival, prevention of chronic
      diseases, assessment of long-term toxicity from HAART, and surveillance for
      additional causes of mortality will become increasingly important.

PMID- 12232846
TI  - Once-daily quadruple-drug therapy with adefovir dipivoxil, Lamivudine,
      Didanosine, and efavirenz in treatment-naive human immunodeficiency virus type 1
      infected patients.
AB  - A 48-week open-label study of 11 antiretroviral-naive, human immunodeficiency
      virus type 1 (HIV-1)-infected adults evaluated once-daily treatment with adefovir
      dipivoxil, lamivudine, didanosine, and efavirenz. At baseline, the median plasma
      HIV-1 RNA level was 4.99 log(10) copies/mL, and the median CD4 cell count was 471
      cells/mm(3). At 24 and 48 weeks after initiation of treatment, median HIV-1 RNA
      levels decreased from baseline by 4.77 and 4.99 log(10) copies/mL, respectively,
      and median CD4 cell counts increased by 135 and 177 cells/mm(3), respectively.
      The regimen was generally well tolerated. No patients withdrew from the study
      because of adverse events. However, 7 patients developed adefovir-related
      nephrotoxicity after >/=20 weeks of treatment; this resolved without sequelae
      after adefovir was discontinued. Overall adherence was 85%. Once-daily quadruple
      drug therapy with adefovir, lamivudine, didanosine, and efavirenz provides
      pronounced and durable suppression of HIV-1 RNA and elevation of CD4 cell counts
      over the course of 48 weeks, with generally good tolerability and adherence.

PMID- 12232847
TI  - Correlation of phylogenetic lineages of group B Streptococci, identified by
      analysis of restriction-digestion patterns of genomic DNA, with infB alleles and
      mobile genetic elements.
AB  - Phylogenetic lineages of pathogenic Streptococcus agalactiae (group B
      streptococci [GBS]) can be identified by analysis of restriction-digestion
      patterns (RDPs) of chromosomal DNA. The purpose of the present study was to
      correlate GBS RDP types and (1) alleles of the highly conserved gene encoding
      translation-initiation factor IF2, infB, and/or (2) the inserted elements IS1548
      and GBSi1. Only 1 combination of serotype and infB allele was found within each
      RDP type. Strains within a particular RDP type also tend to have the same
      inserted elements in each of 3 loci examined. A novel insertion sequence,
      designated "IS1563," was found within all RDP type II-2 strains. Most RDP types
      could be identified by a combination of serotype, infB allele, and inserted
      elements at each of the loci. These molecular markers can be used to identify GBS
      populations and to correlate RDP types and phylogenetic lineages identified by
      different methods.

PMID- 12232848
TI  - Are quinolone-resistant uropathogenic Escherichia coli less virulent?
AB  - The prevalence of hemolysin, type 1 fimbriae, P fimbriae, cytotoxic necrotizing
      factor-1 (CNF-1), aerobactin, and autotransporter toxin (sat) was analyzed by
      polymerase chain reaction and phenotypic assays of 42 epidemiologically unrelated
      Escherichia coli strains causing acute pyelonephritis in women (21 nalidixic acid
      susceptible and 21 nalidixic acid-resistant strains) and 58 E. coli strains
      causing cystitis in women (29 nalidixic acid-susceptible and 29 nalidixic acid
      resistant strains). Hemolysin and CNF-1 were less prevalent (P<.05) in nalidixic
      acid-resistant than in nalidixic acid-susceptible E. coli strains from patients
      with either pyelonephritis (14.3% vs. 52.4%) or cystitis (0% vs. 31.0%). Among E.
      coli strains causing cystitis, type 1 fimbriae expression was less prevalent
      (P<.05) in the nalidixic acid-resistant group (55.2%) than in the nalidixic acid
      susceptible group (86.2%). None of the nalidixic acid-resistant and 20.7% of the
      nalidixic acid-susceptible strains causing cystitis showed the proteolytic toxin
      Sat (P<.05). These results suggest that resistance to quinolones may be
      associated with a decrease in the presence or the expression of some virulence
      factors in uropathogenic E. coli.

PMID- 12232849
TI  - The responsiveness of human V delta 1 gamma delta T cells to Borrelia burgdorferi
      is largely restricted to synovial-fluid cells from patients with Lyme arthritis.
AB  - It has been shown that human gamma delta T cells expressing the V delta 1 T cell
      receptor (TCR) respond to the spirochete Borrelia burgdorferi. Lysates of 3
      Borrelia genospecies triggered the proliferation of peripheral-blood mononuclear
      cells not only from patients with skin manifestations of Borrelia infection and
      from patients with Lyme arthritis but also from healthy donors. However, with the
      exception of 1 patient with Lyme arthritis, no selective expansion of V delta 1
      expressing gamma delta T cells was induced. In contrast, synovial-fluid
      mononuclear cells (SFMC) from 3 of 5 patients with Lyme arthritis responded with
      a selective outgrowth of V delta 1 gamma delta T cells. V delta 1 gamma delta T
      cell lines established from SFMC coexpressed various TCR V gamma chains, although
      V gamma 8 was preferentially used. Thus, the responsiveness to Borrelia antigens
      is not a general property of V delta 1-expressing gamma delta T cells but is
      largely restricted to V delta 1 gamma delta T cells recruited into the inflamed
      tissue.

PMID- 12232850
TI  - Cognitive impairment in adults with good recovery after bacterial meningitis.
AB  - Adults without neurologic sequelae after bacterial meningitis are supposed to
      live without restrictions. Neuropsychological outcome was assessed in 51 adults
      from a prospective cohort with good recovery, defined as Glasgow Outcome Scale
      score 5, after pneumococcal or meningococcal meningitis. Patients who recovered
      well after pneumococcal meningitis showed cognitive slowness (P=.001). A
      cognitive disorder was found in 27% of these patients. Patients who previously
      had meningococcal meningitis were not significantly different from control
      subjects. Scores on general health and quality of life questionnaires revealed
      lower scores for patients with meningitis, which were related to cognitive
      slowing (R, -0.46 to -0.38). In conclusion, adults surviving pneumococcal
      meningitis were at significant risk of neuropsychological abnormalities, even if
      they were clinically well recovered.

PMID- 12232851
TI  - Risk factors for pneumonia in adults with chickenpox.

PMID- 12232853
TI  - Anemia in human immunodeficiency virus infection: the reticulocyte production
      index.

PMID- 12232855
TI  - Preface. Atrial fibrillation in patients undergoing surgery for mitral valve
      disease.

PMID- 12232854
TI  - Histone modifications depict an aberrantly heterochromatinized FMR1 gene in
      fragile x syndrome.
AB  - Fragile X syndrome is caused by an expansion of a polymorphic CGG triplet repeat
      that results in silencing of FMR1 expression. This expansion triggers methylation
      of FMR1's CpG island, hypoacetylation of associated histones, and chromatin
      condensation, all characteristics of a transcriptionally inactive gene. Here, we
      show that there is a graded spectrum of histone H4 acetylation that is
      proportional to CGG repeat length and that correlates with responsiveness of the
      gene to DNA demethylation but not with chromatin condensation. We also identify
      alterations in patient cells of two recently identified histone H3 modifications:
      methylation of histone H3 at lysine 4 and methylation of histone H3 at lysine 9,
      which are marks for euchromatin and heterochromatin, respectively. In fragile X
      cells, there is a decrease in methylation of histone H3 at lysine 4 with a large
      increase in methylation at lysine 9, a change that is consistent with the model
      of FMR1's switch from euchromatin to heterochromatin in the disease state. The
      high level of histone H3 methylation at lysine 9 may account for the failure of
      H3 to be acetylated after treatment of fragile X cells with inhibitors of histone
      deacetylases, a treatment that fully restores acetylation to histone H4. Using 5
      aza-2'-deoxycytidine, we show that DNA methylation is tightly coupled to the
      histone modifications associated with euchromatin but not to the heterochromatic
      mark of methylation of histone H3 at lysine 9, consistent with recent findings
      that this histone modification may direct DNA methylation. Despite the drug
      induced accumulation of mRNA in patient cells to 35% of the wild-type level, FMR1
      protein remained undetectable. The identification of intermediates in the
      heterochromatinization of FMR1 has enabled us to begin to dissect the epigenetics
      of silencing of a disease-related gene in its natural chromosomal context.

PMID- 12232856
TI  - Intraoperative alternatives for treating atrial fibrillation associated with
      mitral valve disease: introduction.

PMID- 12232857
TI  - The significance of atrial fibrillation ablation in patients undergoing mitral
      valve surgery.
AB  - Atrial fibrillation is present in close to 50% of all patients undergoing surgery
      for mitral valve disease.(1-3) However, surgical correction of atrial
      fibrillation in patients with other cardiac pathology that requires surgical
      intervention such as mitral valve disease was never considered as a standard
      approach. The Maze procedure for the treatment of atrial fibrillation was
      introduced in 1987 and was performed safely in hundreds of patients with
      excellent outcomes.(4-7) As a result, several centers have begun to combine the
      Maze procedure with other cardiac procedures, especially mitral valve surgery,
      without adding undue operative risk to patients.(8) When properly performed, the
      results with this combined approach have been excellent.(9,10)

PMID- 12232858
TI  - The technology in use for the surgical ablation of atrial fibrillation.
AB  - The purpose of this article is to present and evaluate the various technologies
      recently developed for the surgical treatment of atrial fibrillation as
      alternatives or adjuncts to the traditional Maze III procedure and other "cut and
      sew" techniques. The discussion contains a detailed consideration of the
      biophysical background of the most common ablation techniques, their mode of
      tissue injury, the methods of use, and the related complications through a review
      of the existing literature and analysis of experimental results. All of the
      current technologies presented are still being tested to augment the success
      rates and reduce the incidence of complications, although all are not available
      for clinical use. Radiofrequency and cryoablation have been used clinically on
      large numbers of patients with varying results. Microwave technology has been
      used in small groups of patients, and the results are to be evaluated. Laser
      technology is still in an experimental phase, and the clinical results are
      forthcoming. True transmurality, reduction of operative time, friendly use of
      ablation devices, and substantial reduction of complications appear to be the key
      factors for broad adoption of alternative energy sources for surgical ablation.

PMID- 12232859
TI  - Combined mitral valve surgery and the Maze III procedure.
AB  - Atrial fibrillation is present in approximately 50% of patients undergoing
      surgery for mitral valve disease. In the past, surgeons were forced to ignore
      atrial fibrillation when performing open-heart surgery for other indications
      simply because there was no proper surgical solution and little awareness of the
      medical consequences of atrial fibrillation. The Maze procedure was introduced in
      1987 and when properly performed, its results when combined with mitral valve
      surgery have been excellent, with no increase in perioperative morbidity and
      mortality and with documented long-term advantages over simply leaving patients
      with atrial fibrillation. In this study we evaluated our recent results in 53
      patients undergoing mitral valve surgery in combination with the Maze III
      procedure. Our results indicate that the Maze III procedure is just as safe and
      effective in controlling atrial fibrillation associated with mitral valve disease
      as it is in controlling atrial fibrillation not associated with mitral valve
      disease.

PMID- 12232860
TI  - Radiofrequency ablation of atrial fibrillation during mitral valve surgery.
AB  - Twenty-three patients underwent endocardial radiofrequency ablation of atrial
      fibrillation (AF) during mitral valve procedures with a previously described left
      atrial lesion pattern. A temperature-controlled 7-coil surgical probe delivered
      60-second lesions at 80 degrees C. The left atrial appendage was oversewn after
      ablation. Ages ranged from 28 to 88 years. Nineteen patients had chronic AF that
      was present for over 1 year in 74%; 12 patients had rheumatic mitral stenosis.
      Mean left atrial diameter was 5.4 +/- 0.7 cm. There was 1 operative death
      unrelated to the ablation, and no strokes or ablation-related complications were
      observed. At mean follow-up of 32.5 weeks, 86% of the 22 survivors were in sinus
      rhythm. All 18 patients with left atrial diameter <6 cm are in sinus rhythm. All
      postoperative atrial flutter was transient, and no patients required subsequent
      transcatheter ablation. This lesion pattern is safe and effective when applied in
      the method described here. It appears to be a reasonable alternative to the
      complete Maze 3 lesion pattern in patients with mitral valve disease.

PMID- 12232861
TI  - Combined atrial fibrillation and mitral valve surgery using radiofrequency
      technology.
AB  - Recently, intraoperative radiofrequency ablation of the left atrium combined with
      mitral valve surgery has become widely used. In our center, 30 patients underwent
      this combined procedure; median sternotomy was used in 16 patients, and port
      access was used in 14 patients. At hospital discharge, 18 patients (60%) were no
      longer in atrial fibrillation, and at 6 months, 19 patients (65%) remained in
      sinus rhythm. All sinus rhythm patients had a well-defined transmitral A wave
      detectable by echocardiography. One patient sustained a major stroke. Two
      patients required pacemaker implantation. Such encouraging preliminary results
      have triggered worldwide interest in the percutaneous and surgical treatment of
      atrial fibrillation. However, the excellent long-term results with the classic
      Cox-Maze III operation have not yet been achieved with these newer approaches.
      Further basic and clinical research is required before a predictable simple and
      safe technique can be introduced as a new standard for the surgical treatment of
      atrial fibrillation in patients with or without structural heart disease.

PMID- 12232862
TI  - Combined atrial fibrillation and mitral valve surgery using microwave technology.
AB  - Atrial fibrillation is associated with a significant morbidity and mortality and
      is typically related to patients with mitral valve disease. Microwave ablation is
      a new option for surgical treatment of chronic atrial fibrillation. We present
      our experience with surgical treatment of mitral valve disease and microwave
      ablation in patients with chronic atrial fibrillation. In 105 patients (73 women,
      32 men, 68.6 +/- 8 years of age from 45 to 83 years, ejection fraction 28% to
      80%, left atrial diameter 56 +/- 9.1 mm from 35 to 97 mm) with mitral valve
      disease, chronic atrial fibrillation was documented for 8.6 +/- 6.8 years.
      Microwave ablation was performed using a continuous ablation line starting at the
      posterior mitral valve annulus and incorporating the interior of all pulmonary
      veins. In 33 patients, mitral valve reconstruction was performed. Ten patients
      received biologic valve replacement; 3 of them got a stentless quattro mitral
      valve prosthesis. Survival rate was 99.1% (n = 104). In the 6-month follow-up, 42
      of 69 patients were in sinus rhythm (61%); in the 1-year follow-up, 37 of 64
      patients were in sinus rhythm (57.8%). Microwave ablation is a safe and efficient
      method for surgical treatment of chronic atrial fibrillation in patients with
      mitral valve disease.

PMID- 12232863
TI  - Microwave ablation for surgical treatment of atrial fibrillation.
AB  - Microwave energy is a relatively new energy modality that is being used for
      surgical atrial ablation as a treatment of atrial fibrillation. Microwave energy
      works by dielectric heating and has a favorable thermal profile that permits both
      rapid endocardial and epicardial ablation. The device is also extremely flexible
      and can be easily adapted to minimally invasive applications. The device has been
      used in over 600 patients with a success ranging from 70% to 90% and without any
      device-related complications. Many of these patients have had their ablations
      performed from the epicardium on the beating heart without the aid of
      cardiopulmonary bypass. Microwave atrial ablation is likely to become an
      important part of the surgical armamentarium, particularly for those performing
      minimally invasive approaches to cure atrial fibrillation.

PMID- 12232864
TI  - The solitary pulmonary nodule: accurate diagnosis allows appropriate treatment.

PMID- 12232865
TI  - The solitary pulmonary nodule: a primer on differential diagnosis.
AB  - Despite significant advances in noninvasive imaging techniques, management of the
      solitary pulmonary nodule (SPN) remains a challenge for chest physicians.
      Patients with SPNs are frequently asymptomatic, and the physical examination is
      seldom revealing. Accurate diagnosis is essential, because >50% of patients will
      require prompt disease-specific therapy. The complexity of the problem is best
      appreciated by reviewing the differential list, which includes nearly 80 distinct
      clinical entities. Consequently, a thorough understanding of the more common
      etiologies is necessary to adequately treat patients with SPNs.

PMID- 12232866
TI  - The pulmonologist's perspective regarding the solitary pulmonary nodule.
AB  - The pulmonologist's goal in managing a patient with a solitary pulmonary nodule
      is to distinguish the benign from malignant nodule and, where malignancy is
      either confirmed or strongly suspected, to expedite resection. By using
      established clinical features (eg, age, smoking status) and radiographic findings
      (eg, calcification, growth rate, size), a probability of malignancy can be
      determined. If necessary, noninvasive or adjuvant invasive testing is used to
      alter the probability to one that permits observation or demands resection. The
      proper use of these tests mandates knowledge about their performance
      characteristics. Decision-analytic approaches, using Bayesian analysis, may
      assist with the calculation of probability. These models have not consistently
      outperformed the clinician or adjuvant testing. The use of low-dose computed
      tomography (CT) scanning as a screening tool has led to the discovery of many
      small, indeterminate nodules. Management decisions for these nodules are
      influenced by their low prevalence of malignancy and small size. Future advances
      will add to our ability to effectively meet our stated goal.

PMID- 12232867
TI  - Radiologic evaluation of the solitary pulmonary nodule.
AB  - The radiologic evaluation of solitary pulmonary nodules can be a complex process.
      Modalities, which can be used, include the chest radiograph, computed tomography,
      and positron emission tomography scanning. Interventional radiology can also play
      a role with image-guided transthoracic needle aspiration of indeterminate
      pulmonary nodules. The primary role of radiologic evaluation is to try to
      differentiate benign from malignant pulmonary nodules. The imaging findings that
      can be helpful in making this distinction as well as the limitations of each of
      the modalities are discussed. For the purpose of this review, solitary pulmonary
      nodule mimics such as skin or rib lesions, vascular malformations, and areas of
      rounded atelectasis are not discussed.

PMID- 12232868
TI  - PET scanning and the solitary pulmonary nodule.
AB  - The finding of a solitary pulmonary nodule on a chest radiograph is a common
      problem in pulmonary medicine and is seen in about 1 in 500 chest radiographs. Of
      the benign lesions, 80% are infectious granulomas, 10% are hamartomas, and the
      remaining 10% are caused by a variety of rarer disorders including noninfectious
      granulomas and other benign tumors. The prevalence of malignancy ranges from 10%
      to 68% in the literature. Because of the high prevalence of malignancy and the
      poor survival for lung cancer, early detection, characterization, and directed
      treatment are important. Positron emission tomography with 18-Fluorodeoxyglucose
      (FDG-PET) can play an important role in the evaluation and management of solitary
      pulmonary nodules. This includes improved characterization of solitary pulmonary
      nodules with very high negative predictive value and improved staging information
      when performed in association with CT, especially for nodal staging and
      identification of unsuspected stage IV disease. PET also provides additional
      information for management of solitary pulmonary nodules by estimating the
      probability of malignancy.

PMID- 12232869
TI  - Fine needle aspiration of the solitary pulmonary nodule.
AB  - Percutaneous transthoracic needle biopsy is a well-established method of
      obtaining cytologic and histologic samples from a pulmonary nodule. Properly
      performed, needle biopsy is a simple and safe procedure. Pneumothorax is the most
      common complication, which, if symptomatic or large, is easily treated by chest
      tube insertion or aspiration. Minor hemorrhage and hemoptysis is the other common
      complication, which is rarely serious. Rare complications include air embolism
      and needle tract metastases. Needle biopsy has a high sensitivity and specificity
      for malignancy. For benign lesion, a specific diagnosis is less common, although
      with core needle biopsy, the yield of a specific benign diagnosis is increased.

PMID- 12232870
TI  - Management of the subcentimeter pulmonary nodule.
AB  - The most sensitive imaging modality for detection of pulmonary nodules is
      computed tomography (CT). Advances in radiologic techniques not only increase the
      number of nodules detected, but also the nodules that are identified are smaller.
      With increased use of spiral CT for lung cancer screening, there will be more
      subcentimeter pulmonary nodules (SCPNs) that will require further diagnostic
      workup. Radiologic evaluation including repeat observational CT or CT contrast
      enhancement should be performed. Bronchoscopic or needle biopsy of the majority
      of SCPNs is not practical. VATS is possible for SCPNs but should be performed in
      a controlled manner to reduce the resection of benign lesions. An SCPN management
      algorithm is necessary to expedite resection of a malignant lesion and to
      minimize removal of benign disease.

PMID- 12232871
TI  - Management of the solitary pulmonary nodule: directed resection.
AB  - The primary goals in management of a solitary pulmonary nodule are: 1) early
      detection and treatment of lung cancer at a curable stage; 2) avoidance of
      unnecessary surgery for benign lesions; 3) efficient, economic use of resources
      in distinguishing between benign and malignant lesions. Management depends on the
      nature of the nodule, the nature of the patient, and the approach of the
      physician or surgeon who assumes responsibility for further evaluation and
      treatment of the solitary pulmonary nodule. By combining appropriate diagnostic
      studies, and close personal attention, unnecessary excision of benign nodules can
      be kept to a minimum, patient anxiety allayed and excision of cancers undertaken
      with appropriate staging and without compromise of outcome.

PMID- 12232872
TI  - The solitary pulmonary nodule: aggressive excisional strategy.
AB  - Treatment of cancer at an early stage leads to enhanced survival. Low-dose spiral
      computed tomography (CT) scanning is readily available and allows early detection
      of solitary pulmonary nodules. Thoracic surgeons should embrace a calculated yet
      aggressive approach to early definitive diagnosis of solitary pulmonary nodules.
      Sputum cytology, bronchoscopy and biopsy, image-guided fine-needle aspiration
      cytology, and positron emission tomography with (18)fluorodeoxyglucose (FDG-PET)
      scanning are useful diagnostic tools, but problems unique to each and the
      possibility of false-negative examination have relegated their use to selected
      nodules. Serial radiographic examination remains the main noninvasive test for
      diagnosis of solitary pulmonary nodules. Video-thoracic surgery allows resection
      of pulmonary nodules with minimal morbidity and mortality. Today, diagnosis by
      excisional biopsy is an acceptable management strategy as more and smaller
      nodules are being detected but not diagnosed. In 2002, when in doubt, we should
      take out the solitary pulmonary nodule.

PMID- 12232874
TI  - The nymphal-adult molt of the silverleaf whitefly (Bemisia argentifolii): Timing,
      regulation, and progress.
AB  - The developmental progress of silverleaf whitefly (Bemisia argentifolii) 3rd
      instars and 4th instar/pharate adults was monitored using a tracking system that
      had been designed to identify synchronous individuals in another species of
      whitefly, the greenhouse whitefly, Trialeurodes vaporariorum. When reared on
      greenbean under conditions of LD 16:8 and a temperature of 26 +/- 2 degrees C,
      the body depth of 3rd instar SLWFs increased from approximately 0.04 mm (Stage 2)
      to 0.175-0.2 mm (Stage 7-8) and the body depth of the 4th instar increased from
      approximately 0.1 mm (Stage 1) to 0.25-0.30 mm (Stage 4-5). The durations of the
      3rd instar and the 4th instar/pharate adult were approximately 3 and 7 days,
      respectively. Examination of coronal sections of 4th instars revealed that adult
      eye and wing development are initiated during Stage 6, the stage in which an
      external examination showed that the eye has begun to undergo pigment diffusion.
      Ecdysteroid titers peaked at approximately 400 fg/ micro g protein during stages
      4 through 6A of the 4th instar, i.e., just prior to and upon the initiation of
      the pharate adult stage. Although adult development is initiated later in the
      SLWF than in the GHWF (adult eye and wing development begin in Stages 4 and 5,
      respectively, in GHWFs), the same rapidity of metamorphosis is observed in both
      species. Within approximately 24 h, the simple bi-layered wing bud developed into
      a deeply folded wing of nearly adult proportions and within an additional 12-24
      h, the nymphal eye and wing bud had been replaced by the well-differentiated eye
      and wing of the adult whitefly. Our study is the first to describe the
      regulation, timing, and progress of the nymphal-adult molt and of the structural
      changes that accompany nymphal-adult metamorphosis in the SLWF.

PMID- 12232873
TI  - Age-dependent response to insecticides and enzymatic variation in susceptible and
      resistant codling moth larvae.
AB  - Insecticide resistance in the codling moth, Cydia pomonella, partly results from
      increased metabolic detoxification. The aim of this study was to follow the age
      variations in larval susceptibility to deltamethrin and teflubenzuron in one
      susceptible (S) strain, and two resistant (Rv and Rt) ones selected for
      resistance to deltamethrin and diflubenzuron, respectively. The age variation of
      the activities of cytochrome P450-dependent monooxygenase (MFO), glutathione S
      transferases (GST), and esterases in S and both resistant strains were
      simultaneously investigated. The highest levels of insecticide resistance were
      recorded in late instars in both resistant strains, although Rv neonates
      exhibited enhanced resistance to deltamethrin. The involvement of an additional
      deltamethrin-specific mechanism of resistance, which could be mainly expressed in
      early instars, was supported by previous demonstration of a kdr point mutation in
      the Rv strain. The cross-resistance between deltamethrin and teflubenzuron
      indicated the involvement of non-specific metabolic pathways in resistance to
      teflubenzuron, rather than target site modification. A positive correlation
      between enhanced GST activities and deltamethrin resistance suggested that this
      mechanism might take place into the adaptive response of C. pomonella to
      pyrethroids treatments. Enhanced MFO activity was recorded in each instar of the
      two resistant strains compared to the susceptible one. But these activities were
      not correlated to the responses to deltamethrin nor to teflubenzuron. In the
      light of these findings, studying age-dependence of responses to selection is
      central to the implementation of monitoring tests of resistances, especially if
      the target instars are difficult to collect in the field.

PMID- 12232875
TI  - Cloning and expression of 32 kDa ferritin from Galleria mellonella.
AB  - We have sequenced a cDNA clone encoding 32-kDa ferritin subunit in the Wax Moth,
      Galleria mellonella. The 32-kDa ferritin subunit cDNA was obtained from PCR using
      identical primer designed from highly conserved regions of insect ferritins. RACE
      PCR was used to obtain the complete protein coding sequence. The 32-kDa ferritin
      subunit encoded a 232 amino acid polypeptide, containing a 19 leader peptide. The
      iron-responsive element (IRE) sequence with a predicted stem-loop structure was
      present in the 5'-untranslated region of the wax moth 32-kDa ferritin subunit
      mRNA. The 32-kDa sequence alignment had 78 and 69% identity with Manduca sexta
      and Calpodes ethlius (G), respectively. The G. mellonella ferritin subunits
      showed minimal identity with each other (19%). The glycosylation site (Asn-X
      Ser/Thr) was found in the 32-kDa subunit but not in the 26-kDa subunit. Northern
      blot analysis showed that the mRNA expression of the 32-kDa ferritin was detected
      in the fat body and midgut. The fat body expression increased after 6 h and the
      mRNA in midgut dramatically increased about 3-fold the expression level at 12 h
      after iron feeding. Western blot revealed that a protein level of the 32-kDa
      subunit is abundant in midgut after 12 and 24 h iron feeding.

PMID- 12232877
TI  - Killing people.

PMID- 12232876
TI  - Significance of penetration, excretion, and transovarial uptake to toxicity of
      three insect growth regulators in predatory lacewing adults.
AB  - Topical treatment of the predatory lacewing adults, Chrysoperla carnea (Stephens)
      (Neuroptera: Chrysopidae) before and after the onset of oviposition with
      diflubenzuron (DFB) at doses based on the maximum field recommended concentration
      resulted in a total inhibition of egg hatch due to death of the embryo. In
      contrast, pyriproxyfen (PYR) and tebufenozide (TEB) did not affect fecundity and
      egg fertility. To explain these differences in toxicity, the patterns of
      penetration through the cuticle, distribution inside the insect body, and
      excretion were studied using [(14)C]-labeled isotopes of each insect growth
      regulator (IGR). Penetration of DFB and TEB reached about 16 and 26% in 7 days,
      whereas 88% of PYR had penetrated in 24 h. However, the rate of excretion for PYR
      was very high, compared to that of DFB and TEB. Low amounts of absorbed
      radioactivity were recovered from the female body with the exception of DFB, the
      ovaries and the eggs deposited during a week. DFB and PYR concentration reached a
      peak in the eggs deposited at the fourth and second day after treatment,
      respectively. The current data indicate the importance of penetration through the
      insect cuticle. However, other mechanisms are likely to be involved in the
      selectivity of the current IGRs towards this beneficial insect.

PMID- 12232878
TI  - Detrusor instability with equivocal obstruction: A predictor of unfavorable
      symptomatic outcomes after transurethral prostatectomy.
AB  - AIMS: To elucidate whether preoperative urodynamic findings can predict outcomes
      of transurethral resection of the prostate (TUR-P). METHODS: Sixty-two patients
      with symptomatic benign prostatic hyperplasia were categorized in three different
      ways based on findings of preoperative pressure-flow study (PFS) and cystometry:
      urodynamic obstruction (determined by the Abrams-Griffiths nomogram), detrusor
      instability (DI), and combination of both. Outcomes of TUR-P regarding symptom,
      function, and quality of life (QOL) were analyzed by changes in the International
      Prostate Symptom Score (I-PSS), maximum flow rate in uroflowmetry, and QOL index
      before and after TUR-P, respectively. Overall outcome was defined as success when
      all of the three categories showed successful improvement. RESULTS: Neither
      urodynamic obstruction alone nor DI alone predicted outcomes of TUR-P. However,
      symptomatic and overall outcomes were significantly worse in patients who were
      not obstructed but had DI. Postoperative persistent DI was more frequently noted
      in patients without clear obstruction (60%) than in those with obstruction (27%).
      Patients with equivocal obstruction showed less satisfactory symptomatic outcomes
      of TUR-P when DI was accompanied. Persistent DI might be the principle cause of
      unfavorable outcomes. CONCLUSIONS: Preoperative evaluation of DI is of benefit
      because it enhances predictive value of the PFS.

PMID- 12232879
TI  - Data from frequency-volume charts versus maximum free flow rate, residual volume,
      and voiding cystometric estimated urethral obstruction grade and detrusor
      contractility grade in men with lower urinary tract symptoms suggestive of benign
      prostatic hyperplasia.
AB  - AIMS: To examine associations of data from frequency-volume charts with maximum
      free flow rate, residual volume, and voiding cystometric estimated urethral
      obstruction grade and detrusor contractility in men with lower urinary tract
      symptoms suggestive of benign prostatic hyperplasia (BPH). METHODS: The 160 men
      included in the study met the criteria of the International Scientific Committee
      on BPH, i.e., they voided more than 150 mL during uroflowmetry, their residual
      volume and prostate size were estimated, and they completed frequency-volume
      charts correctly. From the frequency-volume charts, voiding habits and fluid
      intake were evaluated. Pressure-flow studies were performed as well. RESULTS:
      Increasing residual volume was related to a decrease of maximum voided volume and
      to a decrease of maximum free flow rate. Cystometric capacity was little affected
      by residual volume. Low contractility did not result in high residual volume. A
      marked decrease in voided volumes with increasing obstruction grade was observed,
      due to a decrease of cystometric capacity and an increase of residual volume.
      Detrusor contractility was little associated with voided volumes. A higher
      voiding frequency was related to a higher fluid intake. However, increased
      standardized frequency (number of voidings per 1,000 mL) was associated with a
      substantial reduction of fluid intake. CONCLUSIONS: Infravesical obstruction is
      the most important factor influencing voided volumes, cystometric capacity, and
      residual urine volume. Frequency of voiding was not influenced significantly
      because patients with small voided volumes minimized their fluid intake.

PMID- 12232880
TI  - Short-term reproducibility of cystometry and pressure-flow micturition studies in
      healthy women.
AB  - AIMS: To evaluate the reproducibility of cystometry and pressure flow studies in
      women. We wanted to explore any clinically relevant effect of repeated, same
      session cystometry. METHODS: Thirty healthy women with a mean age of 52 years
      were investigated with repeat medium-fill water cystometry and pressure-flow
      micturition studies in a single session. RESULTS: Large test-retest variability
      was noted, with wide limits of agreement. Of statistical significance was an
      increase of first desire (FD) and normal desire (ND), and a decrease in bladder
      opening pressure. Maximum cystometric capacity was unchanged. CONCLUSIONS:
      Although the nature of the conditioning effect of the first fill remains to be
      explored, the phenomenon could possibly be used for improved urodynamic
      diagnosis.

PMID- 12232881
TI  - Morbidity after ambulatory urodynamics.
AB  - AIMS: To identify urinary symptoms and morbidity after ambulatory urodynamics.
      METHODS: One hundred consecutive women underwent ambulatory urodynamics for a
      variety of urinary complaints. Urinary symptom questionnaires were collected
      before investigation and again 48 hours later, reporting dysuria and haematuria.
      Women were screened for urinary tract infection before investigation and again 48
      hours later. RESULTS: Of the 91 women who completed the study, 1 (1.1%) had a
      positive urinary culture after the investigation but was asymptomatic. Seventeen
      women reported mild to moderate de novo dysuria. CONCLUSIONS: Urinary symptoms
      and morbidity after ambulatory monitoring is low.

PMID- 12232882
TI  - Clinical, urodynamic, and manometric findings in women with combined fecal and
      urinary incontinence.
AB  - AIMS: To determine the prevalence of fecal incontinence in patients with urinary
      incontinence, who were referred for urodynamic evaluation, and to compare
      clinical and manometric findings between double incontinence and isolated fecal
      incontinence. METHODS: Nine hundred women with urinary and/or fecal incontinence
      were prospectively investigated. Patients with double incontinence (group 1) were
      compared with 38 women with isolated fecal incontinence (group 2). Clinical data
      regarding obstetric and urogynecologic history, bowel habit, and type of fecal
      incontinence were collected. Urodynamics and anal manometry were performed.
      RESULTS: Seventy-eight patients (8.7%) presented double incontinence. A history
      of vaginal delivery and chronic straining was more frequent in patients with
      double incontinence (P=0.043). No differences were found in the severity of fecal
      incontinence. Physical examination showed a greater prevalence of rectocele (54%
      vs. 12%) in group 1. On urodynamics, 80% of women with double incontinence had
      stress urinary incontinence. Rectal sensation testing revealed a significantly
      higher rate of hyposensitivity in group 2 (22% vs. 43%). CONCLUSIONS: This study
      supports a close association between combined stress urinary and fecal
      incontinence, history of vaginal delivery, and chronic straining.

PMID- 12232884
TI  - Questionnaires for women with urinary symptoms.
AB  - AIMS: To identify the characteristics of optimal symptom questionnaires in women
      with lower urinary tract symptoms (LUTS). METHODS: Literature review. RESULTS:
      Although numerous questionnaires have been developed for the evaluation of female
      LUTS, no one instrument has emerged as that preferred for collecting and
      reporting subjective information about LUTS in women. Questionnaires currently
      available range widely in intended purpose, extent and style, and in the quality
      of testing used to validate them. CONCLUSIONS: Questionnaires should be
      constructed based on scientifically sound validation techniques that reflect
      disease and/or symptoms in the target population. They should be concise, easily
      administered and scored, discriminant between sphincter and bladder causes of
      incontinence, and able to measure severity and the effect of the symptom on the
      patient.

PMID- 12232883
TI  - Tension-free vaginal tape for stress urinary incontinence: Is there a learning
      curve?
AB  - AIM: To assess the learning curve characteristics of the first 30 tension-free
      vaginal tape (TVT) procedures carried out in our medical center and to evaluate
      its safety and short-term effectiveness. METHODS: A total of 30 incontinent women
      with urodynamically proven SUI were enrolled. None had undergone any previous
      anti-incontinence procedure. All were operated on by one surgeon, in accordance
      with the technique described by Ulmsten et al. in 1996. Mean follow-up was 11.4+/
      3.6 months (range, 5-17 months). RESULTS: Five (17%) bladder perforations
      occurred at the beginning of the study, due to inadvertent insertion of the
      applicator. All perforations were identified by intraoperative cystoscopy. Five
      other patients (17%) had increased intraoperative bleeding (>200 mL)
      necessitating vaginal tamponade. Blood transfusions were not required. Eight
      (27%) patients had immediate postoperative voiding difficulties, necessitating
      catheterization for 2-10 days, but none needed long-term catheterization. There
      was no local infection or rejection of the Prolene tape was found. All patients
      were subjectively cured of their stress incontinence; however, urodynamic
      evaluation revealed "asymptomatic genuine stress incontinence" in one patient.
      Sixteen of 21 patients (80%) with preoperative urge syndrome, had persistent
      postoperative symptoms. No patient developed de novo urge incontinence.
      CONCLUSION: The TVT operation is a new, minimally invasive surgical procedure
      with excellent short- and medium-term cure rates. However, there is a definite
      learning curve, and we believe that the operation should only be performed by
      experienced surgeons.

PMID- 12232885
TI  - Compliance with recommendations of the urodynamic society for standards of
      efficacy for evaluation of treatment outcomes in urinary incontinence.
AB  - The Urodynamic Society (US) published (1997) minimal standards to assess the
      efficacy of therapy for urinary incontinence (UI). The standards were developed
      by a US committee and were approved by the American Urological Society. The
      objective of our study was to evaluate compliance with these standards in recent
      UI research studies. A MEDLINE search was conducted for all articles in which
      outcomes of treatment for UI were reported (November, 1997-October, 1999).
      Reported data were compared with the recommended minimum standards including pre-
      and posttreatment data. Compliance rates for each data field were calculated by
      percentages for (1) the individual article and (2) overall compliance rate among
      all articles. A total of 39 articles that reported treatment for UI were
      selected. The treatments included various surgical procedures, injectables,
      pharmacologic treatments, and mechanical valves. Overall compliance for each
      article varied between 0% and 100%. Only one article met all 100% of the
      recommendations and one met none. The overall mean compliance rate for each
      article was 29%. We conclude that there is far less than optimal reporting of
      outcomes for treatment of UI per the recommendations of the Urodynamic Society.
      This low compliance makes standardized evaluation of treatment outcomes of UI
      difficult if not impossible. We suggest that initiation of funded cooperative
      clinical trials may improve the standardization in UI.

PMID- 12232887
TI  - Normal variation and influence of stress, caffeine intake, and sexual activity on
      uroflowmetry parameters of a middle-aged asymptomatic cohort of volunteer male
      urologists.
AB  - AIMS: To assess normal variations of uroflowmetry in middle-aged asymptomatic
      male urologists and to analyse the influence of stress, caffeine intake, and
      sexual activity. METHODS: Thirty-one male urologists from Quebec and Ontario were
      recruited for this study. All were healthy, not taking any current medications
      known to interfere with lower urinary tract function, and symptom-free
      (International Prostate Symptom Score less than 5). Each received two identical
      flowmeters to keep over a period of 2 weeks, one at home and one in his busiest
      office. Ten uroflow tracings, with a volume greater than 150 mL, were requested
      from each of them; five at home and five in the office. A total of 310 flows were
      analysed. The subjective level of stress, coffee intake, and sexual activity, in
      the hour before each uroflowmetrogram, was recorded, through a short self
      administered questionnaire and stress visual scale. RESULTS: are presented as an
      average per individual. The voided volume was 331.9 mL, with an SD of 94.8 mL.
      The voiding time was 32.7 seconds (SD=15.5). The peak flow rate was 20.5 mL/sec
      (SD=3.9), the mean flow rate was 14.3 mL/sec (SD=3.0), and the time to maximum
      flow was 7.2 sec (SD=4.0). Subjective levels of stress did not significantly
      change these parameters. Uroflows were obtained with and without coffee drinking.
      The voided volume was 337.4 mL (SD=109.2) vs. 290.8 mL (SD=77.3) (P=0.03), and
      peak flow rate 19.4 mL/sec (SD=4.1) vs. 18.9 mL/sec (SD=3.1) (P=0.49),
      respectively. CONCLUSIONS: Uroflowmetry parameters and voided volume are highly
      variable in a normal asymptomatic population. Subjective stress level does not
      seem to have an influence on these parameters. Coffee intake significantly
      increases the voided volume but does not change the peak flow rate. These
      conclusions should be considered when using uroflowmetry parameters as an outcome
      measure.

PMID- 12232886
TI  - Effects of pelvic floor muscle training on strength and predictors of response in
      the treatment of urinary incontinence.
AB  - AIMS: The objectives of this study were (1) to determine the effect of training
      on pelvic floor muscle strength; (2) to determine whether changes in pelvic floor
      muscle strength correlate with changes in continence; and (3) to determine
      whether demographic characteristics, clinical incontinence severity indices, or
      urodynamic measures predict response to pelvic floor muscle training. METHODS:
      One hundred thirty-four women with urinary incontinence (95=genuine stress
      incontinence [GSI]; 19=detrusor instability [DI]; 20=mixed incontinence [GSI+DI])
      were randomized to pelvic floor muscle training (n=67) or bladder training
      (n=67). Urinary diaries, urodynamic evaluation, and vaginal pressure measurements
      by using balloon manometry were performed at baseline and after 12 weeks of
      therapy. Primary outcome measures consisted of incontinent episodes per week and
      vaginal pressure measurements. RESULTS: Both treatment groups had a reduction in
      incontinent episodes (P</=0.004). Vaginal pressures increased more with pelvic
      floor muscle training than with bladder training (P=0.0003). Other than a weak
      correlation between a reduction in incontinent episodes/week and an increase in
      maximum sustained vaginal pressure in women with GSI (r=0.32, P=0.04), there were
      no significant correlations between increases in pelvic floor muscle strength and
      improvement in continence status. There were no significant correlations between
      baseline demographic characteristics, clinical incontinence severity, or
      urodynamic measures and increases in vaginal pressure or improvement in clinical
      severity after pelvic floor muscle training. CONCLUSIONS: Pelvic floor muscle
      training improves continence and increases vaginal pressure measurements, but the
      direct correlations between these alterations are weak. A woman's response to
      behavioral treatment does not depend on her demographic characteristics, clinical
      incontinence severity, urodynamic measures, or initial pelvic floor muscle
      strength.

PMID- 12232888
TI  - c-Fos expression in the spinal cord after acute sacral segmental nerve
      stimulation.
AB  - AIMS: Sacral nerve stimulation (SNS) can provide subjective and objective relief
      of pelvic pain and chronic voiding symptoms, but its mechanism is poorly
      understood. It is well known that a noxious stimulus applied to one part of the
      body can reduce the response to a subsequent stimulus elsewhere in the body. This
      phenomenon, known as diffuse noxious inhibitory controls (DNIC), seems to be the
      mechanism by which pain can be reduced by concurrent noxious stimulation.
      METHODS: On the basis of the DNIC concept, we investigated the expression of a
      protein product of proto-oncogene c-Fos (c-Fos) in the rat spinal cord after
      acute electrical stimulation of the sacral segmental nerve with or without lower
      urinary tract irritation. Adult male Sprague-Dawley rats were treated either by
      sacral nerve stimulation (SNS) from the S1 sacral foramen or chemical irritation
      of the lower urinary tract (LUT) or both. Rats were perfused transcardially, and
      spinal cords were removed and processed for c-Fos immunohistochemistry. c-Fos
      expression in the central nervous system was detected by immunohistochemistry by
      using the avidin-biotin technique. The number of c-Fos-positive cells and their
      locations in the spinal cord were evaluated. RESULTS: SNS and LUT irritation
      resulted in significant increases in c-Fos-positive cells in L6 and S1 spinal
      segments. In the animals treated by SNS and LUT irritation, counts of c-Fos
      positive cells in L6 and S1 segments were significantly smaller than expected.
      Distribution and number of c-Fos-positive cells in rats that received SNS and LUT
      irritation were almost the same as those induced by SNS alone in the S1 segment.
      CONCLUSIONS: SNS alone caused a near maximal response in c-Fos expression such
      that adding LUT irritation did not cause a linear increase in c-Fos. Subsequent
      LUT irritation could not induce additional expression of c-Fos within the spinal
      cord.

PMID- 12232889
TI  - Selective block of urethral sphincter contraction using a modified Brindley
      electrode in sacral anterior root stimulation of the dog.
AB  - AIMS: Patients with spinal cord injury often present with dysfunction of urinary
      bladder and urethral sphincter. One treatment option is sacral rhizotomy and
      sacral anterior root stimulation with the Finetech Brindley stimulator. However,
      a major disadvantage is the lack of selective stimulation, resulting in
      simultaneous contraction of sphincter and bladder followed by unphysiological
      micturition. This study investigated the possibility of selective bladder
      stimulation by using a Brindley electrode. METHODS: In 11 male anaesthetized
      foxhounds, a complete posterior rhizotomy was perormed. The anterior S2 roots
      were stimulated with different quasi-trapezoidal (QT) pulses (pulse length range,
      600-1,400 microsec; stimulation current, 0.1-2.0 mA; frequency, 20 Hz) by using a
      tripolar Brindley electrode. Sphincter and bladder pressures were measured
      urodynamically. RESULTS: All 11 animals showed a maximal reduction of the highest
      sphincter pressure over 80%, and in 6 of 11 trials, the sphincter pressure was
      inhibited completely (100%). With stimulations at maximal sphincter blockade, the
      average achievable bladder pressure was 33.48 cm H(2)O higher than the average
      sphincter pressure, and in three cases, a strong micturition was observed.
      Selective blockade of the sphincter was possible by applying QT pulses. The
      bladders remained uninfluenced by this blockade and kept their excitability at
      any time. CONCLUSIONS: This study shows that selective bladder stimulation with
      little or no coactivation of the sphincter is possible. A physiological
      micturition can be achieved by using a tripolar Brindley electrode. Introduction
      of this stimulation technique into clinical practice should not face major
      difficulties, considering that the device is an established electrode.

PMID- 12232890
TI  - Biochemical and morphological effects of bladder pumping on the urinary bladder
      in rats.
AB  - AIMS: To study the influence of bladder pumping on the urinary bladder in 44
      female rats. METHODS: Under halothane anesthesia, a urethral catheter was
      inserted into the bladder of 27 rats, and air (0.4-0.8 mL) was pumped in and out
      of the bladder at 0.5 cycles/second for a period of 5 minutes. Twenty-four hours
      after pumping, the bladder was harvested for measurement of the tissue levels of
      myosin, actin, and nerve growth factor, as well as for electron microscopy. In
      nine of the 27 rats, cystometry was performed without anesthesia before and 1, 7,
      30, and 90 days after bladder pumping. The remaining 17 rats that did not undergo
      pumping were anesthetized and their bladders were harvested as a control.
      RESULTS: Bladder pumping increased the bladder capacity and decreased the maximum
      bladder contraction pressure, but did not increase the residual volume. Bladder
      pumping also increased the tissue level of nerve growth factor and decreased the
      levels of myosin and actin. Electron microscopy showed degeneration of bladder
      smooth muscle cells and nerve fibers after bladder pumping, as well as
      derangement and disruption of collagen fiber bundles in the bladder wall. These
      functional and morphological effects of pumping disappeared within 90 days.
      CONCLUSIONS: Bladder pumping therapy appears to have various effects on the
      bladder wall collagen fiber bundles, smooth muscle cells, and nerves.

PMID- 12232891
TI  - Comparison of the experience with acute and chronic electrically stimulated
      detrusor myoplasty.
AB  - AIMS: To evaluate the acute and chronic urodynamic effects of electrically
      stimulated detrusor myoplasty in dogs. METHODS: Eight female mongrel dogs were
      studied acutely and six dogs chronically (0 to 12 weeks postoperatively).
      Bladders were wrapped with the rectus abdominis muscle, keeping an intact blood
      supply and at least two intercostal nerves of the flap preserved. Bladders were
      electrically stimulated with bipolar electrodes inserted into the muscle.
      Urodynamics and post void residual were measured post operatively in the acute
      studies and every 2 weeks for 3 months in chronic studies. RESULTS: Acutely, the
      increase in intravesical pressure was 45+/-7 cm H(2)O, which resulted in a
      postvoid residual of 26+/-3%. In the chronic study, increases of intravesical
      pressure sufficient to empty the bladder during myoplasty electrical stimulation
      were not sustained, although detrusor compliance and flap viability were
      preserved. CONCLUSIONS: The electrically stimulated detrusor myoplasty worked
      well acutely to increase vesical pressure sufficient to empty the bladder, but
      the chronically stimulated myoplasty did not maintain efficient bladder emptying
      primarily due to electrode problems. Further studies with improved electrode
      material and placement are required before clinical application of the
      electrically stimulated detrusor myoplasty can be assessed.

PMID- 12232892
TI  - Price survey. Contracts key to foley stability.

PMID- 12232893
TI  - Aurora moves to achieve 100% online purchasing.

PMID- 12232894
TI  - GHX, Broadlane form latest e-commerce linkup.
AB  - Broadlane agreed in June to connect its electronic commerce system to the
      supplier-owned site run by GHX. As a result, contract compliance could either
      improve or be more easily evaded, depending on hospitals' response to the wider
      choice of suppliers.

PMID- 12232895
TI  - Repairers must relabel instruments, court rules.
AB  - A federal appeals court decided that repair companies must be sure that
      endoscopic instruments they have worked on, especially those they have
      drastically altered, must be clearly identified as such. In some cases, that
      could mean that the original manufacturer's name must be removed, or the
      repairer's name added to the device's label.

PMID- 12232896
TI  - Strengthening system security to prepare for HIPAA.

PMID- 12232897
TI  - Choosing clinical IT tools that matter for physicians. How hospitals view the
      selection of CIS tools will influence physician adoption and physician
      recruitment well into the future.

PMID- 12232898
TI  - It's all about process. Focusing on improving the process rather than eliminating
      the paper is the key to reducing administrative costs.

PMID- 12232899
TI  - Walking through healthcare with a purpose. The key to a successful DM program is
      the right technology fit with both providers and patients.

PMID- 12232900
TI  - Healthy hearts. Minneapolis HMO achieves documented health gains with technology
      and patient self-management.

PMID- 12232901
TI  - Fertile fields. The healthcare sector represents an enormous prospective
      purchaser of security solutions. But the solutions that healthcare organizations
      choose--and why they choose them--reflect a portrait of organizations with plenty
      of ramp-up potential.

PMID- 12232902
TI  - Integrating new data sources. The next step for clinical decision support systems
      will bring greatly expanded capabilities to healthcare providers and
      organizations.

PMID- 12232903
TI  - Accent on access. Ambulatory health center improves physicians' productivity by
      giving them flexible access to their patients' records.

PMID- 12232904
TI  - What works. Scanning the future. Scanning and workflow help a clinical lab access
      and process information in hours instead of days.

PMID- 12232905
TI  - What works. Extreme storage. A single "super server" consolidates business files
      once housed on more than 100 smaller machines.

PMID- 12232906
TI  - Clinical information systems hotlist.

PMID- 12232907
TI  - A matter of trust.

PMID- 12232908
TI  - Employee success management: a cure for the staffing crisis?

PMID- 12232909
TI  - Hospital construction boom looms, changes to affect facilities' design.

PMID- 12232910
TI  - Analyst report: Blues plans to be even bigger players in years ahead.

PMID- 12232911
TI  - Broad-based coalition to create healthcare IT standards.

PMID- 12232912
TI  - HFMA industry study highlights importance of revenue-cycle management.

PMID- 12232913
TI  - If you suspect drug abuse.

PMID- 12232914
TI  - Homing in on nursing home codes.

PMID- 12232915
TI  - EMR? Not exactly. Good enough? For now.

PMID- 12232916
TI  - The penalty for bearing false witness.

PMID- 12232917
TI  - I knock on patients' doors.

PMID- 12232918
TI  - "The lawyers are running amok".

PMID- 12232919
TI  - Full-body scans--or scams?

PMID- 12232920
TI  - Hospital hardball.

PMID- 12232921
TI  - Practicing solo, but not alone.

PMID- 12232922
TI  - Music, medicine, and money for charity.

PMID- 12232923
TI  - When a health plan isn't a health plan.

PMID- 12232924
TI  - Life may be better without a white coat.

PMID- 12232925
TI  - Moving consumers to the head of the class.

PMID- 12232926
TI  - A voice in the wilderness cries elderly get too much.

PMID- 12232927
TI  - Lobbyists that the founders just never dreamed of.

PMID- 12232928
TI  - Examining costs of chronic conditions in a Medicaid population.
AB  - PURPOSE: To compare health care costs and their components in patients with
      chronic illnesses. DESIGN: Quasi-experimental retrospective database analysis of
      an integrated state-Medicaid dataset. METHODS: Nine chronic illnesses and 28 two
      disease combinations were evaluated in 284,060 patients. Dependent variables were
      total cost and the component costs (hospital, physician, home health and medical
      supplies, and pharmacy). Statistical analysis included analysis of variance
      (ANOVA) and multiple analysis of variance (MANOVA). RESULTS: The nine chronic
      illnesses studied were: psychosis, depression, cardiovascular illness, congestive
      heart failure, diabetes, acid peptic illness, respiratory illness/asthma,
      hypertension, and anxiety. Psychosis and depression patients had the highest mean
      yearly costs at $6,964 and $5,505, respectively. Highest component costs were
      mental health practitioners for psychosis and hospital costs for depression. All
      other conditions had significantly lower yearly costs. Component costs consisted
      primarily of pharmacy and hospital costs. Psychosis was a component in 5 of the 7
      most costly chronic-disease concurrences. The highest disease-concurrence mean
      cost was for psychosis and depression ($18,318). CONCLUSIONS: The unique resource
      needs of different chronic illnesses should be considered in benchmarking and
      evaluating chronic-disease management programs.

PMID- 12232929
TI  - Mental disorders in medical students at the University of the West Indies,
      Trinidad and Tobago. Audit at a doctor's practice.
AB  - A series of 32 consecutive students from one medical school presenting for
      psychiatric treatment over a two-year period between September 1997 and August
      1999 is described. The author treated 31 of these students, representing 288
      visits and 312 hours. On the basis of retrospective case note reviews, the author
      presents demographic data, the year of medical school in which the illness began,
      DSM IV diagnoses, treatment modalities, time absent from University as a result
      of mental illness and major stressors. Of the 32 subjects, 50% were male, with
      ages ranging from 20 to 34 years (mean 24.9 years). Ninety-four per cent were
      single, and 78% were Trinidadians. Thirty-one per cent were Trinidad and Tobago
      National Scholars. This finding achieved statistical significance. Seventy-two
      per cent presented during their clinical training. The most common source of
      referral was from members of the Faculty of Medical Sciences (31%). Relationship
      issues were the most commonly identified stressors in 31% of the subjects. Mood
      disorders and anxiety disorders were present in 59% of the students.
      Pharmacotherapy was used in 75% of the students. The majority (53%) of medical
      students with mental disorders were absent from university for less than one
      month. At follow-up in July 2001, 26 (81%) of the students had graduated, three
      (9%) were still in medical school and three (9%) had withdrawn from medical
      school as a result of mental illness. The study is limited in that only those
      seeking assistance from one doctor's practice are described. The findings would
      be further explored in longitudinal studies.

PMID- 12232930
TI  - The Postgraduate Diploma in Primary Care and Family Medicine at the University of
      the West Indies, St Augustine, Trinidad and Tobago.
AB  - This paper is a descriptive one and provides the background and programme
      description of the Postgraduate Diploma in Primary Care and Family Medicine at
      The University of the West Indies, St Augustine, Trinidad and Tobago. This time
      efficient model, built on the principles of adult learning, draws on the
      participants' past and present work experiences and uses their present work
      experiences as a source for reflection and change in a student-friendly,
      academic, educational setting. Core courses within the programme include medical
      education, biomedical ethics, evidence-based medicine and communication skills.
      There is also a strong clinical component to the programme.

PMID- 12232931
TI  - Carotid endarterectomy versus percutaneous angioplasty for carotid stenosis.

PMID- 12232932
TI  - Pedicled flaps in reconstructive surgery.
AB  - An audit was conducted of pedicled flaps used in reconstructive surgery in
      Trinidad from 1983 to 2000. This consisted of 65 flaps. There were four cases of
      partial flap necrosis: three involving tram flaps and the other involving the
      metacarpal artery flap. There were no cases of total flap loss. Pedicled flap
      coverage provides immediate closure of potentially difficult wounds. This early
      cover reduces the risk of infection as a result of increasing the blood supply
      and providing a physical barrier. This contributes to a shorter hospital stay and
      earlier rehabilitation. Our present team approach with the inclusion of a
      reconstructive surgeon now allows for uncompromised debridement in trauma and
      oncological resection.

PMID- 12232933
TI  - Persistent gestational trophoblastic disease presenting as left hemiparesis in a
      Jamaican teenager.
AB  - A 19-year-old woman, who delivered a macerated stillborn at 32 weeks' gestation
      and had persistent postpartum vaginal bleeding, presented with a left hemiparesis
      three and a half months after delivery. A clinical diagnosis of persistent
      gestational trophoblastic disease (GTD) was made, based on quantitative serum
      beta-hCG of more than 200,000 IU/ml, cannon ball metastases on chest X-ray and
      two ring enhancing lesions, metastases, in the right parietal lobe on Computed
      Axial Tomography (CAT) scan of the brain. Despite combination chemotherapy, with
      methotrexate, cyclophosphamide and actinomycin D, her condition worsened and she
      died.

PMID- 12232934
TI  - Pancreatitis and duodenal obstruction following abdominal aortic aneurysm repair.
AB  - This paper reports one case of pancreatitis and duodenal obstruction that
      occurred following repair of an abdominal aortic aneurysm. The patient had
      neither antecedent biliary or pancreatic disease nor alcohol abuse. The
      presentation was mild and the patient had an uneventful recovery without surgery.
      We present this uncommon entity and review the available literature.

PMID- 12232935
TI  - Images and diagnoses. Patient 1: Paget's disease. Patient 2: nipple eczma.

PMID- 12232936
TI  - Images and diagnoses. Pulmonary hypoplasia.

PMID- 12232937
TI  - Hypoglycaemia--was it all in the head?

PMID- 12232938
TI  - Diverticulitis of the vermiform appendix.

PMID- 12232939
TI  - Concurrent mucosa-associated lymphoid tissue lymphoma and adenocarcinoma of the
      stomach.

PMID- 12232940
TI  - Smoker: past, present and future?

PMID- 12232941
TI  - Magnetic resonance imaging and stroke.

PMID- 12232942
TI  - Issues in bioethics. Teaching medical ethics to health professionals.
AB  - New medical technologies, public concern about medical ethics, and the advent of
      numerous ethical dilemmas in healthcare have led many medical schools to increase
      their formal teaching of ethics. Ethical issues in healthcare may involve a
      complex mix of scientific, economic, social, cultural, religious, moral and legal
      issues. Education in medical ethics will therefore need to be on-going to
      accommodate changes that periodically occur in healthcare issues, policies, or
      the changing moral values of the society. This article proposes frameworks within
      which this process may occur.

PMID- 12232943
TI  - Jamaica cancer mortality statistics, 1999.
AB  - A total of 2697 cancer-related deaths were documented among Jamaicans for the
      year 1999, accounting for 17.7% of all deaths. Males accounted for 1466 and
      females for 1231. The age-adjusted cancer mortality rate was 171.7 per 100,000
      for males, 122.0 per 100,000 for females and 140.5 per 100,000 for the total
      population. Leading cancer mortality sites for males were prostate, lung and
      stomach and in females, breast, cervix uteri and large bowel. Most deaths were
      recorded in the 55-64 and 65-74 year-age groups. Despite well-established
      cervical cancer screening programmes, the calculated mortality rate for cancer of
      the cervix uteri in Jamaican females (15.8 per 100,000) is approximately two and
      a half times that seen in African-American females.

PMID- 12232944
TI  - Respiratory distress syndrome in Curacao. Conventional versus surfactant
      treatment.
AB  - The aim of this study was to determine the incidence of Respiratory Distress
      Syndrome (RDS) and to evaluate the efficacy of surfactant treatment at the
      Neonatal Intensive Care Unit (NICU) at the St Elisabeth Hospital, Curacao,
      Netherlands, Antilles. This was a retrospective cohort study of 86 infants, with
      moderate to severe RDS, out of 877 newborns admitted to the NICU between 1991 and
      1998. Results of conventional RDS treatment between 1991 and 1994 (n = 54, group
      1) were compared to results of treatment between 1994 and 1998 (n = 32, group 2)
      with surfactant and increased prenatal steroids. The incidence of RDS in group 1
      was 12%, and 7.5% in group 2. Use of prenatal steroids increased from 7.3% (group
      1) to 47% in group 2 (p < 0.05). Twenty-five infants died, 17 (31.5%) in group 1
      and 8 (25%) in group 2. The complication most frequently found in both study
      groups was Bronchopulmonary Dysplasia (BPD): sixteen infants (30%) in group 1 and
      9 infants (28%) in the surfactant-treated group. BPD was significantly associated
      with time on the ventilator in both groups (p < 0.05). We found no cases (0%) of
      Retinopathy of Prematurity (ROP) in group 1, and 3 cases (9%, p < 0.05) in group
      2. We found no differences in other complications between group 1 and 2. The mean
      time between birth and the first surfactant treatment in group 2 was more than
      nine hours. Surfactant rescue treatment in combination with prenatal steroids
      results in lower incidence of RDS and in lower mortality than conventional RDS
      treatment in this study. The increased incidence of ROP in the surfactant-treated
      group was probably the result of better detection. BPD and other complications
      remained unchanged. Earlier surfactant administration is suggested to reduce
      mortality and morbidity in the future.

PMID- 12232945
TI  - Paediatric HIV/AIDS in Jamaica. A hospital-based description.
AB  - The continuing worldwide epidemic of adult HIV/AIDS has led to an increase in the
      number of HIV-positive children mainly through perinatal transmission. Although
      national data are available, there is no published report of the epidemiology of
      HIV/AIDS in children in Jamaica. A multicentre retrospective analysis of 183 HIV
      seropositive children admitted to hospitals in Jamaica between 1990 and 1996 was
      conducted. Ages at diagnosis were available for 172 patients with 61% diagnosed
      in the first year of life. Clinical histories were available for 129 patients
      with the primary presenting symptoms of infected children being failure to
      thrive, pneumonia, diarrhoea, dermatitis and lymphadenopathy. Classification was
      possible in 128 patients: 49 were exposed, 76 were infected and three were
      seroreverters. Infected children had a longer hospital stay than those classified
      as exposed or seroreverters. As of December 31, 1997, 125 patients had defaulted,
      nine patients were alive and 51 were reported dead with a median age of death of
      12 months. From these data, it is estimated that the hospital-based HIV incidence
      among children in Jamaica increased from 0.149 per 10,000 person years in 1990 to
      1.331 per 10,000 person years in 1996. This study demonstrates a rise in the
      estimated incidence of HIV/AIDS but we were unable to estimate survival reliably
      since the data required were not available for 75% of children identified. These
      data highlight the urgent need for targeted interventions to reduce vertical
      transmission of HIV as well as a need for prospective studies to establish
      reliable data on incidence and long-term outcome for HIV-infected children.

PMID- 12232946
TI  - HIV infection seroprevalence and risk factor study among pregnant women attending
      the Antenatal Clinic at the University Hospital of the West Indies, Kingston,
      Jamaica.
AB  - The objectives of this study were to determine the seroprevalence and risk
      factors for Human Immunodeficiency Virus (HIV) infection among the antenatal
      clinic population at the University Hospital of the West Indies (UHWI). Pregnant
      mothers (4186) attending antenatal clinic at the UHWI were screened for HIV
      infection between September, 1998, and October, 2000. Tests were performed with
      the use of Abbott enzyme immunoassay (EIA) kits for the detection of antibodies
      to HIV 1 and 2. Demographic characteristics and risk factor assessments were
      performed using a questionnaire for all positive cases and four randomly selected
      negative controls matched by age to each positive case. Twenty-one women were
      found to be HIV positive. Nineteen of these women were not previously aware that
      they were HIV-positive. The seroprevalence of HIV infection among antenatal
      mothers was 0.5%. The mean age of cases was 29.3 +/- 4.6 years. There was no
      significant difference between cases and controls with regards to parity, socio
      economic status and educational achievement. Women residing in urban Kingston and
      St Andrew (Odds ratio (OR) 5, 95% confidence interval (CI) 1.4, 18), as well as
      those with a higher number of lifetime sexual partners (OR 1.42, 95% CI 1.13,
      1.79) and those with previous sexually transmitted diseases (OR 3.4, 95% CI 1.1,
      10.6) were at greater risk for HIV infection. In contrast, women who commenced
      coitus at a later age were at less risk of becoming infected (OR 0.79, 95% CI
      0.6, 0.97). This study demonstrates a low seroprevalence of HIV in the UHWI
      antenatal population compared to the reported seroprevalence of 2%-8% in pregnant
      women in Latin America and the Caribbean. The results from this study emphasize
      the continuing need for voluntary HIV testing and HIV/AIDS educational campaign
      for this vulnerable group.

PMID- 12232947
TI  - Did exclusive breast-feeding and early discharge lead to excessive bilirubin
      levels in newborns in Antigua and Barbuda?
AB  - Hyperbilirubinaemia is a common neonatal problem worldwide and is the leading
      cause of admission to the Special Care Nursery in Antigua and Barbuda. In 1990,
      the Innocenti Declaration in support of breast-feeding led to the adoption of the
      Baby-Friendly Hospital Initiative in many countries of the Caribbean, including
      Antigua and Barbuda. Comparing 1989 to the years 1992 to 1994, the Special Care
      Nursery at Holberton Hospital experienced a 40% increase in newborns admitted
      with hyperbilirubinaemia (peak total bilirubin > 12 mg/dl or 205 mumol/l). A
      retrospective review of Special Care Nursery and Maternity Ward records was
      undertaken to determine the incidence and aetiology of hyperbilirubinaemia from
      1992 to 1994. There were 3721 infants born in Antigua and Barbuda in those years,
      98% of Afro-Caribbean or mixed ancestry. The overall incidence of peak total
      bilirubin over 12 mg/dl (205 mumol/l) was 12.5% (466/3721), not inconsistent with
      the reported incidence of 8 to 20% in other countries. However, the incidence of
      higher levels of hyperbilirubinaemia in Antigua and Barbuda exceeded those
      reported for other countries. In Antigua and Barbuda, total bilirubin of 15 mg/dl
      (255 mumol/l) or higher was found in 263 of 3721 infants (7.1%) compared to 5.9%
      in India and 2% of breast-fed infants in the United States of America (USA).
      Total bilirubin of 20 mg/dl (340 mumol/l) or higher was seen in 91 of 3721
      infants (2.5%) exceeding reported prevalence in the USA for both African-American
      and Caucasian infants (1%) and equal to the reported prevalence in Asian infants
      (2%). The possible aetiologies of hyperbilirubinaemia in neonates with total
      bilirubin 18 mg/dl (306 mumol/l) or higher in our patients were investigated.
      Medical records of 134 of 156 (86%) infants having this level of
      hyperbilirubinaemia were available for review. The possible reason for
      hyperbilirubinaemia was ABO incompatibility in 4/134 (3%), Rh incompatibility in
      1/134 (1%), prematurity in 12/134 (9%) and sepsis neonatorum in 21/134 (16%). The
      hyperbilirubinaemia was idiopathic in 96/134 (71%) infants. Newborns in Antigua
      and Barbuda were discharged 3.7 days after their mothers' admission, with 50%
      discharged prior to 48 hours of age. Early discharge in developed countries has
      led to increased readmissions for hyperbilirubinaemia. Following the appointment
      of a dietitian to supervise breast-feeding, admissions for hyperbilirubinaemia
      fell by 50% by 1998. These data suggest that exclusive breast-feeding and early
      discharge led to an epidemic of neonatal hyperbilirubinaemia in Antigua and
      Barbuda.

PMID- 12232948
TI  - Socio-demographic and health system factors in relation to exclusive breast
      feeding in Tobago.
AB  - To determine the prevalence and significant correlates of exclusive breast
      feeding among nursing mothers, we conducted a survey among nursing mothers
      attending the Wellness Baby Clinic in Tobago from July 1 to December 1, 1998. A
      random sample of 151 mothers had face-to-face interviews with a standardized
      pretested questionnaire. Our results suggest that 48.3% and 20.8% of infants were
      exclusively breast-fed at two and four months respectively. Univariate logistic
      regression analyses showed that exclusive breast-feeding at two months was
      significantly positively associated with years of schooling completed by the
      mother, frequency of prenatal visits, mode of breast-feeding, mother's knowledge
      of the recommended duration of breast-feeding, and occupation of the child's
      father. Exclusive breast-feeding at four months was significantly positively
      associated with mother's age, years of schooling completed by the mother,
      frequency of prenatal visits, mother's knowledge of the recommended duration of
      breast-feeding, years of schooling completed by the child's father and occupation
      of the child's father. In multivariate logistic analyses, adjusting
      simultaneously for all relevant explanatory variables, exclusive breast-feeding
      at two months was significantly positively associated with frequency of prenatal
      clinic visits, mode of breast-feeding, mother's knowledge of the recommended
      duration of breast-feeding and occupation of the child's father. In addition,
      exclusive breast-feeding at four months was significantly positively associated
      with frequency of prenatal clinic visits, length of hospital stay, mother's
      knowledge of recommended duration of breast-feeding, years of schooling completed
      by the child's father, family structure and inversely associated with mother's
      age. In this sample, parental socio-demographic characteristics and health system
      factors were associated with subsequent infant feeding practices.

PMID- 12232949
TI  - M-mode echocardiographic findings in a contemporary Afro-Caribbean population
      referred for evaluation of congestive cardiac failure.
AB  - Congestive cardiac failure is emerging as a significant public health problem
      around the world, including the Caribbean. Recent reports from developed
      countries suggest that 30 to 40% of patients with congestive cardiac failure have
      normal systolic function. This percentage may be even higher in non-Caucasian,
      non-male populations. This study was undertaken to determine the M-mode
      echocardiographic findings in a current, consecutive series of Afro-Caribbean
      patients referred for congestive cardiac failure. There were 165 patients, 51%
      male, mean and standard deviation (SD) age of 63 +/- 15 years, referred between
      May 1998 and June 2000. Echocardiographic findings included left atrial size
      (LA), left ventricular (LV) end systolic (ESD) and end diastolic dimension (EDD),
      LV posterior wall thickness (PWT) and ventricular septal thickness (VST). LV
      ejection fraction (EF) was derived. LA > 4 cm, PWT or VST > 13 mm and LVEF < 50%
      were considered abnormal. Increased LV wall thickness (LV hypertrophy) only was
      the most frequent finding, 68/165 (41%), consistent with possible diastolic
      dysfunction. If a less restrictive definition for abnormal LV wall thickness, 12
      mm, is used, this finding increases to 79/165 (48%). Decreased LVEF (LV systolic
      dysfunction) was seen in 57/165, (35%) and was seen in significantly more men
      (42% versus 29%, p < 0.01). Valvular disease was seen in 13/165, 8%. Normal
      findings on echocardiography were found in 27/165 (16%), more commonly in women
      (19 versus 8, p < 0.05) and younger patients (54 years versus 65 years, p < 0.05)
      and in only 10% if 12 mm is used for LV wall limit. LV hypertrophy was seen in
      42% of patients (61% if 12 mm is used for LV wall limit) with systolic
      dysfunction. Thus, congestive cardiac failure with LV hypertrophy is the most
      frequent finding in this Afro-Caribbean population, with LV systolic dysfunction
      in only 35% of patients. These findings are consistent with possible diastolic LV
      dysfunction due to hypertension as the primary cause of cardiac failure in the
      population.

PMID- 12232951
TI  - Houses, neighbourhoods and health.

PMID- 12232950
TI  - A survey of essential national health research in nine developing countries.
AB  - A survey of Essential National Health Research (ENHR) was conducted between
      December 1997 and November 1998 in nine developing countries. A total of 27
      respondents from seven South East Asian and two Caribbean countries completed
      questionnaires. Respondents included 14 men and 13 women with a median age of 48
      years (range 25-69 years); 15 were researchers, seven were health providers,
      three policy makers and one a community representative (one no response). ENHR
      was formally adopted in five countries mainly through public policy statements.
      Seven countries had a mechanism in place for promotion of ENHR and national
      meetings were held in five countries in the year prior to the survey. A special
      activity was conducted in order to define health research priorities in eight
      countries and a list of these priorities was available in seven countries. The
      level of ENHR activity was ranked as low or moderate in most countries except
      India and Malaysia which were rated as moderate to high. Three countries reported
      that the process resulted in new or additional funds being made available for
      research, while India reported available funds being reallocated to meet the
      priorities defined. The respondents of six countries said that ENHR networking
      had led to tangible results, including improved collaboration among researchers
      and research institutions and the sharing of resources among different
      organizations (five countries). The ENHR process had resulted in research
      findings being used to formulate or change health policy in five countries. Most
      countries had not produced any new research protocols through the ENHR process.
      However, there were 250 new research protocols in India and 68 in Pakistan, of
      which 20 and between 25 and 35, respectively, were funded and 15 peer reviewed
      articles had been published from India. This survey does suggest that the ENHR
      process may be promoting health research on priority health problems and the use
      of results to formulate policy in selected countries. However, it is too early to
      assess the contribution of ENHR to health and development and a variety of
      different studies would be needed to conduct this assessment.

PMID- 12232952
TI  - Gender inequity and public health. Getting down to real issues.

PMID- 12232953
TI  - Body build from birth to adulthood and risk of asthma.
AB  - BACKGROUND: Few reports aimed at the study of adulthood obesity and asthma have
      taken into account the effects of size at birth and obesity in adolescence. This
      paper examines the combined effect of size at birth and obesity in both
      adolescence and adulthood on the risk of asthma at age 31 years. METHODS: The
      study was derived from a prospectively population-based Finnish birth cohort born
      in 1966, for which data were collected in pregnancy and at various ages.
      Adulthood doctor-diagnosed asthma with current symptoms and results of skin prick
      tests were obtained in 1997. The analysis was limited to 4719 subjects with
      complete information on asthma and atopy and anthropometric measures at various
      ages. RESULTS: Ponderal index at birth had a U-shaped association with adult
      atopy, OR 1.30 (95% CI: 1.11-1.52) for the lowest tertile and OR 1.33 (95% CI:
      1.13-1.55) for the highest tertile, as compared to the middle tertile. The
      association was independent of obesity later in life. Those obese (BMI > or =
      95th percentile) in adolescence (OR 2.09, 95% CI: 1.23-3.57) and in adulthood (OR
      1.99, 95% CI: 1.14-3.47) had a higher occurrence of adult asthma than those with
      BMI < 85th percentile. Both estimates were reduced after mutual adjustment.
      CONCLUSIONS: Size at birth has a long-lasting effect on atopy in adulthood, which
      is independent of weight in adolescence and adulthood. Those who were obese in
      adolescence and adulthood tended to have a higher risk of asthma in adulthood.
      These findings underline the importance of considering the life course of obesity
      in the analyses of asthma and atopy.

PMID- 12232954
TI  - Physical activity and coronary heart disease in older adults. A systematic review
      of epidemiological studies.
AB  - BACKGROUND: While there is good evidence to suggest an inverse relation of
      physical activity and cardiorespiratory fitness with coronary heart disease (CHD)
      in middle-aged men and women, much less is known about this association in older
      adults. The purpose of this paper was to explore the relation of physical
      activity and cardiorespiratory fitness with CHD in older adults by reviewing
      relevant studies. METHODS: Publications were identified in two ways: i)
      conducting a PUBMED search from its inception in 1966 until January 2001; and ii)
      scrutinizing the reference sections of identified papers. RESULTS: Ten studies
      relating physical activity and two relating cardiorespiratory fitness in older
      people to CHD met the inclusion criteria. With one exception, the studies were
      observational in nature and the majority of these were of prospective cohort
      design. Most studies featured men only. Of the eleven studies that presented data
      on older men, eight reported an inverse relation between physical activity or
      cardiorespiratory fitness and CHD, and statistical significance was seen in five
      of these. There were too few data on older women to draw clear conclusions
      regarding the association in this group. CONCLUSIONS: This review suggests that,
      in older adult men, physical activity and cardiorespiratory fitness are inversely
      related to CHD risk. This association is unlikely to be attributable to reverse
      causality or confounding. Except where such advice is contraindicated, older
      adult men may benefit from physical activity in terms of reduced CHD risk.

PMID- 12232955
TI  - Characteristics of suicidal adolescents and young adults presenting to primary
      care with non-suicidal (indeed non-psychological) complaints.
AB  - BACKGROUND: Some young people presenting to primary care experience suicidal
      symptoms that they do not report. METHOD: We conducted a survey of suicidal
      ideation among 15-24-year-old patients presenting to Australian general
      practitioners. RESULTS: Patients who experienced substantial, but unstated,
      suicidal symptoms tended to be female and somewhat younger; their depression and
      distress levels, while not as high as suicidal patients with psychological
      complaints, were nonetheless elevated. CONCLUSIONS: Young patients who evince any
      signs of depression or distress, particularly but not only young females, should
      be evaluated regarding psychological symptoms, including suicidal ideation.

PMID- 12232956
TI  - The role of gender in long-term sickness absence and transition to permanent
      disability benefits. Results from a multiregister based, prospective study in
      Norway 1990-1995.
AB  - BACKGROUND: The aim of the study was to identify predictors for the transition
      from long-term sickness absence into disability pension with a special focus on
      gender. METHODS: The study used data from a national database containing a 10%
      random sample of the Norwegian adult population (The KIRUT database). The study
      population were all individuals in the database who on 1 January 1990 were
      eligible for sick pay from the Norwegian National Insurance System: 83,398 men
      and 75,586 women. Individuals below 60 years with long-term sickness absence
      starting in 1990 and 1991 were identified, 6,434 men and 8,233 women, and
      followed up for three years. Background data were used as independent variables
      in a logistic regression of the probability for receiving disability pension
      during follow-up. RESULTS: Annual cumulative incidence of long-term sickness
      absence was 6.5% for women and 4.9% for men. During follow-up, 12.4% of the women
      and 12.6% of the men received disability pension. Among full-time employed women
      only 10.3% had become disability pensioners, while the corresponding proportion
      for women working part-time was 15.5%. For men the figures were 12.1% (full-time)
      and 18.1% (part-time). In the logistic regression of the whole sample the female
      odds ratio was insignificant. The dominant predictive factors for disability
      pension were age and duration of the sickness spells. Working part-time also
      increased the risk. Higher levels of education and having children below 7 years
      reduced the probability for disability pension. Separate regressions for men and
      women showed that the 'protective' effect of having small children only remained
      for women.

PMID- 12232957
TI  - Influence of commercial information on prescription quantity in primary care.
AB  - BACKGROUND: In the last few years we have witnessed many publicly-financed health
      services reaching a crisis point. Thus, drug expenditure is nowadays one of the
      main concerns of health managers, and its containment one of the first goals of
      health authorities in western countries. The objective of this study is to
      identify the effect of the perceived quality stated in commercial information,
      its uses, and how physicians perceive the influence it has on prescription
      amounts. METHODS: A cross-sectional study of 405 primary care physicians was
      conducted in Galicia (north-west Spain). The independent variables physician's
      education and speciality, physician's perception of the quality of available drug
      information sources, type of practice, and number of patients were collected,
      through a postal questionnaire. Environmental characteristics of the practice
      were obtained from secondary sources. Multiple regression models were constructed
      using as dependent variables two indicators of prescription volume. RESULTS: The
      response rate was 75.2%. Prescription amounts was found to be associated with
      perceived credibility of information provided by medical visitors, regulated
      physician training, and environmental characteristics of the practice (primary
      care team practice, urban environment). CONCLUSIONS: The study results suggest
      that in order to decrease prescription amounts it is necessary to limit the role
      of pharmaceutical companies in physician training, improve physician education
      and training, and emphasize more objective sources of information.

PMID- 12232958
TI  - Hospitalizations among employees in the Danish hotel and restaurant industry.
AB  - BACKGROUND: The aim of the present study was to provide a broad picture of the
      morbidity among employees in the Danish hotel and restaurant industry. METHODS:
      Cohorts of all 20-59-year-old employees in the Danish hotel and restaurant
      industry in the years 1981, 1986, 1991 and 1994 were formed to calculate age
      standardized hospitalization ratios (SHR) and time trends (1981-1997) for many
      different diagnoses. RESULTS: Both for women and men, significantly higher SHRs
      were found for infectious and parasitic diseases, neoplasms, diseases in the
      nervous system and sense organs, diseases of the circulatory system, diseases of
      the respiratory system, diseases of the digestive system and diseases of the
      musculoskeletal system among employees in hotels and restaurants than in the
      digestive system and diseases of the musculoskeletal system among employees in
      hotels and restaurants than in the working population at large. Furthermore,
      among women a significantly elevated risk was found for injuries in the lower
      extremities, injuries in the upper extremities and head injuries, and among men a
      high risk was found for head injuries and a low risk for ruptures in ligaments
      and muscles. The trend assessments did not detect any significant changes in SHRs
      over time. CONCLUSION: Employment in the Danish hotel and restaurant industry is
      associated with an elevated hospitalization risk due to many diseases, which may
      be related to occupation and lifestyle. In line with the official policy of
      reducing inequality in health, focus should be placed on the health problems in
      this group.

PMID- 12232959
TI  - Evidence-based prevention requires evidence-based performance. The case of
      screening for congenital heart disease in child health care.
AB  - STUDY OBJECTIVE: To illustrate to what extent the cost-effectiveness of an
      evidence-based prevention programme may depend on evidence-based performance, by
      the example of screening for congenital heart disease in Dutch child health care.
      METHODS: A patient follow-up study on 290 children with congenital heart disease,
      of which 83 with significant disorders, diagnosed over two years, and born in the
      south west of the Netherlands. RESULTS: Adequate screening for congenital heart
      disease at Dutch child health centres, compared to inadequate screening, proves
      to be effective (OR: 0.18; 95% CI: 0.04-0.87). However only 15% of all patients
      with significant disorders in this study was adequately screened. Total health
      care costs involved over two years amount to over $3 million. Of these costs, 13%
      are to be attributed to screening tests; 8% to referrals resulting from
      screening. The costs for screening and referrals, as they were actually
      performed, are estimated at about $72.000 per patient benefiting from it. Were
      all children to be screened adequately this sum would be reduced to about
      $15.000. CONCLUSION: Not only should prevention programmes be evidence-based, but
      also outcome and quality, monitored by periodically establishing whether they are
      optimally performed.

PMID- 12232960
TI  - Nutrition and inequalities. A note on sociological approaches.
AB  - BACKGROUND: This article provides an overview of three approaches taken to
      illuminate the sociological contribution to the field of nutrition and
      inequalities, in the hope of prompting future researchers to pursue the lines of
      enquiry suggested. APPROACHES: Under the heading of inequalities in food use, the
      paper first exemplifies the utility of 'political arithmetic', possibly the
      sociological approach best known in public health. This includes socio-economic
      patterning in food purchases as well as disadvantage in access, where studies of
      poverty represent a longstanding focus. A rural/urban dimension has, however,
      been left dormant. A second approach is illustrated by work on public
      understandings of nutrition, encompassing primarily small-scale studies of
      beliefs about nutrition, which emphasise the plurality of lay definitions of diet
      and health. Lacking are studies which build on this work to uncover the relation
      to health inequalities. Third to be introduced is sociological work on the social
      distribution of taste, which illuminates the potential for examining enduring,
      shared ideas of styles in eating embedded in forms of the social organisation of
      the home that is associated with different socio-economic levels. CONCLUSION: The
      paper ends with comment on practical implications for public health practice and
      policy designed to reduce inequalities in nutrition.

PMID- 12232961
TI  - Usefulness of a short food frequency questionnaire for screening of low intake of
      fruit and vegetable and for intake of fat.
AB  - BACKGROUND: Simple screening tools to identify intake of fruit, vegetables and
      fat are necessary to design effective public health intervention strategies in
      order to increase intake of fruit and vegetable and to reduce fat intake.
      METHODS: 108 men recorded their food intake for 14 days and filled in a 27-item
      food frequency questionnaire (FFQ) 1.5-2 months later. Estimates of fruit,
      vegetables and fat intake from the FFQ were compared with those from the weighed
      records. RESULTS: Mean intake of vegetables and fruit estimated from the diet
      records increased with increasing categories for frequency of intake assessed by
      the FFQ. Spearman correlation coefficient between frequency of intake of
      vegetables and fruit from the FFQ and amount of these food items estimated from
      the weighed records was 0.46 and 0.66, respectively. The ability of the FFQ to
      predict those having inadequate intake of fruits and vegetables based on weighed
      record data, was more than 90%. Almost 95% who reported use of fat spreads by the
      FFQ also reported this by the records. The correlation coefficient between the
      amount of fat used on bread from the two methods was 0.79. The correlation
      between fat intake estimated from both methods was 0.36 and for saturated fat
      intake the correlation was 0.38. CONCLUSION: The FFQ could be used to screen for
      low consumers of fruit, vegetable and fat spread in intervention programmes.
      However, the ability of the FFQ to identify persons with high (or low) intake of
      fat and saturated fat was not good.

PMID- 12232962
TI  - Alcohol-attributable and alcohol-preventable mortality in Italy. A balance in
      1983 and 1996.
AB  - BACKGROUND: Since the mid-1970s, a striking reduction in alcohol consumption has
      been observed in Italy and other developed countries. Alcohol-related mortality
      in Italy has been estimated for 1983 and 1996. METHODS: Alcohol-attributable and
      alcohol-preventable deaths were estimated by: i) data on prevalence of drinkers
      from two Italian surveys; ii) the parameters of meta-regression models
      investigating the relationship between alcohol intake and the risk of several
      conditions positively and negatively related to alcohol; and iii) the number of
      deaths from 21 alcohol-related conditions. RESULTS: About 68,000 and 42,000
      deaths were attributed to alcohol consumption in 1983 and in 1996 respectively,
      mostly from hemorrhagic stroke, liver cirrhosis, cancer, and injuries. About
      6,600 deaths from coronary heart disease were prevented by alcohol. Light intake
      (25 g/day or less) caused about 30% of deaths attributable to any consumption in
      women. In men, about one-half of the deaths were attributable to the highest
      category of intake (100 g/day or more), while a lower proportion of deaths was
      attributed to light intake (almost 7%). In 1996 the number of the deaths caused
      and those prevented by light intake was approximately the same (5,400 and 5,200
      respectively) and did not significantly differ. CONCLUSION: The estimated number
      of deaths attributable to alcohol consumption in Italy still far exceeds the
      number prevented for both women and men. Despite the cardiac protective effect,
      alcohol consumption remains a major public health problem in Italy. Both
      population and high risk strategies in preventing alcohol-related problems should
      be implemented.

PMID- 12232963
TI  - Methadone maintenance treatment, criminality and overdose-related deaths. An
      ecological study, 1983-1999.
AB  - BACKGROUND: Methadone maintenance treatments (MMTs) are the commonest
      substitution treatments offered to opiate addiction in Switzerland, in order to
      reduce criminal behaviour, infectious disease transmission and overdose death.
      METHOD: To investigate the relationship between the increase in the number of
      methadone maintenance treatments, criminal activity of addicts and overdose
      related deaths, an ecological study was undertaken in the Canton of Geneva, from
      1983 to 1999. RESULTS: The regular and extensive increase in the number of MMTs
      is not significantly associated, during the 1983-1999 period, with a fall either
      in drug addict incarcerations or in overdose-related deaths. However, a slight
      decrease is observed in the number of imprisoned opiate addicts since 1994, and a
      marked decrease is seen in overdose deaths from 1997 on. An important and stable
      number of these deaths is due to methadone itself. CONCLUSION: Public health
      objectives to diminish delinquency and overdose deaths cannot solely be fulfilled
      by extensive use of MMTs. A positive result could appear when access to MMT is
      highly favoured. This hypothesis must be proved correct by observational studies
      conducted on a general population.

PMID- 12232964
TI  - Heroin-assisted treatment as a response to the public health problem of opiate
      dependence.
AB  - Injection drug use (involving the injection of illicit opiates) poses serious
      public health problems in many countries. Research has indicated that injection
      drug users are at higher risk for morbidity in the form of HIV/AIDS and Hepatitis
      B and C, and drug-related mortality, as well as increased criminal activity.
      Methadone maintenance treatment is the most prominent form of pharmacotherapy
      treatment for illicit opiate dependence in several countries, and its application
      varies internationally with respect to treatment regulations and delivery modes.
      In order to effectively treat those patients who have previously been resistant
      to methadone maintenance treatment, several countries have been studying and/or
      considering heroin-assisted treatment as a complementary form of opiate
      pharmacotherapy treatment. This paper provides an overview of the prevalence of
      injection drug use and the opiate dependence problem internationally, the current
      opiate dependence treatment landscape in several countries, and the status of
      ongoing or planned heroin-assisted treatment trials in Australia, Canada and
      certain European countries.

PMID- 12232965
TI  - Heroin maintenance and attraction to treatment.

PMID- 12232966
TI  - Tobacco smoking as a form of child abuse.

PMID- 12232967
TI  - A history of psychiatric ethics.
AB  - In the not-far-distant past, ethics for all doctors was, at best, an ill-attended
      lecture or two on how to keep out of trouble; it was assumed the rest was
      absorbed by a form of social and professional osmosis. Although ethics has
      entered the undergraduate curriculum, continuing medical education programs,
      journals, and books, it still is in a state of flux. Although immense progress
      has been made in the last 30 to 40 years, much remains to be done. Trainees are
      often naive, and the older generation is on a steep learning curve. An
      encouraging feature is the current lively debate on matters ethical and how they
      can best be incorporated into everyday clinical practice. The long-held notion of
      ethics resting complacently in the paternal arms of Hippocrates has, with almost
      brutal haste, been projected into a rapidly evolving modern world of technologic,
      moral, and societal change. Yet, at its core, ethics has to retain its humanism
      and guard against influences from every quarter that tries to make it a set of
      rules, thereby negating the diversity and uniqueness of our patients. Even as you
      read, there will be new influences and pressures on clinical practice that have
      an ethical dimension. For instance, we are adjusting to new privacy laws in
      Australia that allow patients, whether public or private, access to their
      psychiatric records. Globalization is not restricted to world trade; it also
      operates in the framework of societal change and the wider dissemination and
      implementation of libertarian views. If such "freedoms" are not currently
      available to patients, they soon will be. This brief historical foray in
      identifying some of these forces can assist in their early recognition so that as
      a profession, we are forewarned and forearmed and, in that respect, be ahead of
      both Henry Ford ("History is more or less bunk...") [42] and the Bourbons ("They
      learn nothing and they forget nothing") [43].

PMID- 12232969
TI  - Ethical considerations in the integration of religion and psychotherapy: three
      perspectives.
AB  - The authors maintain that the integration of religion in psychotherapy is, at
      best, problematic and requires a respect for boundaries, but that the integration
      of a nonreligious but spiritual psychotherapy consisting of the three elements
      identified above (attention to the person, not the disease, considering one's
      work as vocation, and the pursuit of empathic understanding) is a therapeutic
      necessity and an ethical duty. The authors speak with distinct voices in the
      three major sections of the article but come to remarkably similar conclusions:
      (1) the ability to inquire into the religious and spiritual life of patients is
      an important element of psychotherapeutic competency; (2) information about the
      religious and spiritual lives of patients often reveals extremely important
      information; (3) the inquiry process must communicate respect and curiosity for
      this dimension of the patient's life even (and perhaps especially) when the
      content is at variance from that of the therapist; and (4) there is significant
      potential for therapeutic abuse when the therapist communicates in a manner
      reflecting a personal agenda that abandons the principle of psychotherapeutic
      neutrality. One area of potential disagreement came as the authors considered the
      possibility of different combinations of faith disciplines and therapy in
      designated religious settings that all parties recognize as such. One author
      (G.P.M.) believes that such combinations in these settings may be ethically
      permissible. The other two authors are concerned about such combinations because
      of the powerful but covert factor of transference in healing relationships. The
      authors eventually decided that this question was beyond the scope of the article
      and limited themselves to discussions about psychotherapy in secular settings.
      They each advocate the systematic inclusion of spiritual assessment as a core
      competency for psychotherapy education. In a way similar to the exploration of
      any deeply personal dimension of human experience, integrating spiritual and
      religious dimensions of our patients' lives into their treatment requires
      consummate professionalism, the highest quality of knowledge, skills, and
      attitudes, and thorough grounding in a sophisticated biopsychosocial model.

PMID- 12232968
TI  - Ethics and mental illness research.
AB  - There are many tasks ahead in the area of ethics and mental illness research. We
      face unknown challenges in psychiatric genetics projects, studies of
      psychopharmacological interventions in children, controversial scientific designs
      (e.g., symptom challenge, medication-free interval), and cross-disciplinary
      research incorporating goals and methods of health services, epidemiology, and
      social and behavioral science endeavors. Boundaries between innovative clinical
      practices and research-related experimentation will become increasingly difficult
      to distinguish, as will the roles between clinicians, clinical researchers, and
      basic scientists. Moreover, the institutions and systems in which research occurs
      are being rapidly and radically revised, raising new questions about oversight
      responsibilities and standards. Our ability to identify and respond to the
      ethical questions arising in this uncharted territory will depend on our
      willingness to self-reflect, to integrate the observations and insights of the
      past century, to think with great clarity, and to anticipate novel ethical
      problems that keep company with scientific advancements. It will also depend on
      data. Empirical study of ethical dimensions of human research is essential to
      anchor and attune the intuitions and theoretical constructs that we develop.
      Science and ethics have changed over the past 100 years, as they will over the
      next century. It is ironic that the ethical acceptability of psychiatric research
      is so much in question at this time, when it holds so much promise for advancing
      our understanding of mental illness and its treatment. The tension between the
      duty to protect vulnerable individuals and the duty to perform human science will
      continue to grow, as long as ethics and science are seen as separable, opposing
      forces with different aims championed by different heroes. The profession of
      psychiatry is poised to move toward a new, more coherent research ethics paradigm
      in which scientific and ethical issues are recognized as inextricably linked:
      science as a human activity carries complex ethical meanings and
      responsibilities, and ethics itself is subject to scrutiny and amenable to
      scientific inquiry. Building a broader, more versatile, and more effective
      repertoire of safeguards will be increasingly important, and safeguards, in this
      view, represent a modest price for the privilege of studying serious illnesses-
      diseases that cause grave suffering and yet are a source of both vulnerability
      and strength. In this paradigm, attention to ethics safeguards is no longer
      understood as a barrier to scientific advancement, but rather as the means by
      which psychiatric research may be conducted with broad societal support,
      honorably and, ultimately, with the expectation of bringing benefit to millions
      of people with mental illness.

PMID- 12232970
TI  - Ethics in managed care.
AB  - The current era of managed costs and care create ethical dilemmas based on
      economic constraints and incorporation of principles of distributive justice.
      Traditional ethical concerns related to confidentiality, conflicts of interest,
      double agentry, and honesty are complicated by interference in the doctor-patient
      relationship caused by intrusive utilization management. National health reform
      must take these issues seriously to ensure that the cure promised by such reform
      efforts is not worse than the disease. The challenge for psychiatrists is to
      adapt to these constraints without losing sight of traditional ethical medical
      positions. If the ethics become diseased, then no cure may exist at all.

PMID- 12232971
TI  - The ethical and legal implications of Jaffee v Redmond and the HIPAA medical
      privacy rule for psychotherapy and general psychiatry.
AB  - The 1996 Jaffee v Redmond US Supreme Court decision established a privilege for
      psychotherapeutic communications in the federal courts. The new privilege has
      both substantive and symbolic importance. In its strongly worded opinion in
      Jaffee v Redmond, the US Supreme Court made clear that confidentiality in
      psychotherapy takes precedence over certain other important societal goals. The
      new Health Insurance Portability and Accountability Act (HIPAA) medical privacy
      rule promulgated by the Department of Health and Human Services relies on Jaffee
      v Redmond in providing additional legal protections for confidential
      psychotherapy. Both the US Supreme Court's Jaffee v Redmond ruling and the HIPAA
      rule support the ethical protection of confidentiality of conversations between
      psychiatrists and patients.

PMID- 12232972
TI  - Non-sexual boundary crossings and boundary violations: the ethical dimension.
AB  - The ethical principles relative to nonsexual boundary issues derive from the
      first principle of respect for the dignity of the patient. Using a case vignette,
      the authors have explored the mutual derivation and inter-relations of these
      principles, with clinical approaches to patient care. Clinicians should be aware
      of the ethical underpinnings of sound therapeutic techniques that manifest
      respect for the patient.

PMID- 12232973
TI  - Post-termination sexual boundary violations.
AB  - In this essay, the author has focused on the rationale for an absolute
      prohibition of sexual contact between psychiatrists and former patients. The role
      of an ethics code is to proscribe professional misconduct that may have the
      potential to harm the patient. Because we know that in many cases of psychiatrist
      patient sex there is serious exploitation of the patient's vulnerability, we have
      clear prohibitions against sexual relations between a current patient and his or
      her psychiatrist. The same considerations apply to former patients. The
      transference (and countertransference) feelings established in the relationship
      persist well beyond termination. Even in the absence of a treatment that
      acknowledges the existence of transference, a power differential is unmistakable
      because of the fiduciary nature of the relationship. Moreover, the therapeutic
      relationship is effective because it will never be anything but a treatment
      relationship. The possibility of a future sexual affair between psychiatrist and
      patient erodes the conditions necessary for effective psychiatric therapy.
      Finally, most patients will feel the need to return to treatment at some point in
      the future, and the psychiatrist needs to preserve that potential as part of the
      duty to the patient. For all of these reasons, the current position of the APA on
      an absolute prohibition against sex with former patients is a sound and sensible
      one.

PMID- 12232974
TI  - Ethical issues in treating gay and lesbian patients.
AB  - Since the 1973 decision to remove homosexuality from the list of mental
      disorders, most mental health practitioners have shifted their clinical focus
      from "the cure" of homosexuality to treating the concerns of gay and lesbian
      patients. Some clinicians, however, reject the mental health mainstream's view
      and continue to conceptualize homosexuality as a mental disorder. Their clinical
      theories have been incorporated into wider societal debates regarding the status
      of gay and lesbian people. The sexual conversion or reparative therapies they
      practice, however, may include routine ethical violations in the realm of
      improper pressure, confidentiality, informed consent, and fiduciary
      responsibility to the patient's best interest. On the other hand, a
      normal/identity approach to treatment, particularly in its most reductionistic
      forms, may involve ethical lapses in the areas of informed consent and fiduciary
      responsibility to the patient's best interests as well.

PMID- 12232975
TI  - Ethics and forensic psychiatry.
AB  - This article has attempted to outline some of the important ethical issues faced
      by the psychiatrist in the forensic role. Much of forensic psychiatry is
      practiced by general psychiatrists without specific forensic training who must
      thereby familiarize themselves with the problem areas likely to be encountered in
      this work. They should also be knowledgeable about the ethics guidelines prepared
      by forensic psychology and forensic psychiatry organizations that are subject to
      frequent modification. Ethical problems often occur when psychiatrists exceed
      their expertise, their role as contracted, or the actual facts in the case.
      Psychiatric experts usually represent just a small part of most litigation, and
      an attitude of humility rather than grandiosity is appropriate. Expert witnesses
      serve as educators rather than decision makers in the case [21]. Given the
      complexity and uncertainty of medical decision making generally, whether in
      clinical or forensic medicine, forensic psychiatric opinions should be
      appropriately qualified by their limitations, acknowledged affirmatively rather
      than only on cross-examination. Expert witnesses commonly take an oath to "tell
      the truth, the whole truth." Forensic psychiatrists are not experts in moral
      matters and should not be rendering moral judgments or misusing their authority
      as psychiatrists to advance their own political or social ideology [19].
      Testimony should be based on data and theory generally accepted in the
      profession, recognizing that there will always be minority views. Psychiatrists,
      however, should not be testifying based upon idiosyncratic views unsupported by
      at least a respectable minority of the profession. As in clinical psychiatry,
      complex or challenging forensic cases often require consultation from a
      knowledgeable colleague.

PMID- 12232976
TI  - Ethical considerations in psychiatric profiling of political figures.
AB  - Questions concerning such matters as the effects of health and alcoholism on
      Boris Yeltsin's decision making; the mind of the Unabomber; the psychology and
      decision making of Saddam Hussein of Iraq, who was initially characterized by the
      US Government as "the madman of the Middle East"; the psychology of David Koresh
      and the Branch Davidians, who were involved in an extended siege with the Bureau
      of Alcohol, Tobacco, and Firearms and the Federal Bureau of Investigation that
      ended tragically on April 19, 1993; and, most recently, the psychology of the
      nineteen al-Qaeda terrorists responsible for the tragic events of September 11,
      2001 in which they claimed thousands of lives while giving their own, "killing in
      the name of God," and of their charismatic leader Osama bin Laden have led
      journalists to turn to social scientists, including psychiatrists, to offer
      commentary on public figures.

PMID- 12232977
TI  - Ethical considerations in the relationship between physicians and the
      pharmaceutical industry.
AB  - Persuasion, influence, and change are familiar domains in psychiatry. Frequently,
      therapists attempt to identify and understand the cognitions, affects, and
      perceptions their patients have developed or acquired and then, by a number of
      means, trigger therapeutic changes. Whereas they spend much work in the
      therapeutic setting attempting to delineate the mechanisms that produce such
      transformations and to influence change, physicians are often in a similar
      relationship with the pharmaceutical industry. However, in this relationship,
      they are the recipients of persuasion and influence.

PMID- 12232978
TI  - The ethics of e-mail communication in psychiatry.
AB  - In both medicine and science, practice has historically preceded ethical scrutiny
      and legal regulation. Recent examples include the debates over stem cell research
      and cloning. The technology existed and was in the initial stages of study prior
      to the sounding of alarms by ethicists and lawmakers. The same state of affairs
      has occurred with the use of electronic (E)-mail in psychiatric practice. The
      convenience and possibilities of E-mail have already entered into the practice of
      physicians without pause to consider the ethical implications: specifically,
      those related to privacy and confidentiality. The authors do not discuss the more
      questionable uses of the Internet such as physician prescribing to patients they
      have not evaluated face to face. In this article, the authors confine their
      discussion to situations in which E-mail communication is used as an adjunct to
      ongoing face-to-face meetings.

PMID- 12232979
TI  - [Duodecim 2002--growth without pain].

PMID- 12232980
TI  - [MARS].

PMID- 12232981
TI  - [Mental disorders and their drug treatment in a patient with HIV infection].

PMID- 12232982
TI  - [Hypopituitarism and hepatitis as complications of nephropathia epidemica].

PMID- 12232983
TI  - [Meeting a patient with hypochondria].

PMID- 12232985
TI  - [On reference values].

PMID- 12232984
TI  - [Unclear syncope].

PMID- 12232986
TI  - [Myeloma as a bone tumor].

PMID- 12232987
TI  - [Infertility--an increasing problem?].

PMID- 12232988
TI  - [Development of methods and legislation of reproductive medicine].

PMID- 12232989
TI  - [Basic infertility diagnostic tests].

PMID- 12232990
TI  - [Use of ultrasonography in the diagnostics of infertility].

PMID- 12232992
TI  - [Choosing the treatment for infertility].

PMID- 12232991
TI  - [Insulin resistance and infertility].

PMID- 12232993
TI  - [Single embryo transfer reduces pregnancy risks].

PMID- 12232994
TI  - [Prevention of infertility].

PMID- 12232995
TI  - [The agony of infertility].

PMID- 12232996
TI  - [Surgical treatment of refractive disorders].

PMID- 12232997
TI  - [Personality disorders and brain imaging].

PMID- 12232998
TI  - [ASA therapy or not?].

PMID- 12232999
TI  - [Popular treatment recommendations].

PMID- 12233000
TI  - [Pandemic influenza still a threat--where do we get the vaccine from?].

PMID- 12233002
TI  - [Should the second generation antipsychotic agents be used as drugs of choice?].

PMID- 12233003
TI  - [Cognition disorders after cerebrovascular accidents].

PMID- 12233001
TI  - [Mandatory bicycle helmet use is a good thing].

PMID- 12233004
TI  - [The diabetic heart].

PMID- 12233005
TI  - [How well are national practice guidelines known at health care centers?].

PMID- 12233006
TI  - [Massive fetomaternal bleeding--an insidious and serious pregnancy complication].

PMID- 12233007
TI  - [Clinical significance and imaging diagnostics of enlarged vestibular aqueduct].

PMID- 12233008
TI  - [Necrosis of the nose tip].

PMID- 12233009
TI  - [Pseudotumor and biopsy].

PMID- 12233010
TI  - [Without liver transplantation paracetamol intoxication is often be lethal, in
      spite of N-acetylcysteine therapy].

PMID- 12233012
TI  - Barcoding in health care.

PMID- 12233011
TI  - Information technology in health care: it's about privacy, patient care and
      getting paid.
AB  - While the healthcare provider industry's adoption of information may be
      considered to be slow, there are thousands of efforts to put technology to work
      to improve the bottom line and the missions of healthcare organizations.
      Healthcare Leadership & Management Report has published case studies of
      information technology implementation in recent issues and we would like to hear
      from healthcare leaders about their experiences with IT implementation success or
      failure. We will be happy to accept written submissions, or we will work with
      your staff to write the story so that our readers may benefit from your
      experience.

PMID- 12233013
TI  - Internal Marker. This little piggy....
AB  - The government's proposals for a new fixed-price market could mean that many
      trusts will make significant losses. Policy must balance the need to protect some
      trusts from the effects of fixed prices with the desire for financial incentives
      with 'bite'. The basis on which prices are struck is crucial. Quality will need
      careful monitoring.

PMID- 12233014
TI  - Microbiological contamination of pipeline installations.

PMID- 12233015
TI  - Towards 'Star Wars' technology.

PMID- 12233016
TI  - Full circle to in-house facilities services.
AB  - Careful consideration must be taken prior to in-sourcing in order to ensure that
      the decision is right for the organisation. There will be pressure to go for the
      quick fix, or the option that involves the least pain or takes the least time
      (this may be a knee jerk reaction to go straight back out to the market).
      Contractors will be alert to this due to market intelligence and as a result one
      problem may be solved but a number of others created as the organisation is put
      over yet another barrel. Before any decision is taken, an analysis of the
      circumstances relating to the outsourced services will need to be undertaken.
      There are several stages to go through when considering in-sourcing and on the
      whole the steps will mirror those that need to be considered when outsourcing
      services in the first instance. It is important to recognise that the change
      management process associated with in-sourcing services will need to be carefully
      managed. This point cannot be stressed enough. In-sourcing will require
      management of the outgoing contractor, the in-house team and the customers during
      the mobilisation phase. A facilities strategy that is aligned to the
      organisation's strategic direction--sharing core values and goals alongside a
      good specification are essential. To ensure services are delivered as specified,
      a robust and effective monitoring system will need to be developed and put into
      operation. Just as all organisations are different, the drivers influencing the
      in-sourcing decision will be different--with factors relevant to the host
      organisation. If in-sourcing has been thoroughly and carefully considered there
      is absolutely no reason why it should not be effective (as long as it is
      specified, resourced, managed and monitored in an appropriate manner). In
      sourcing is now being considered as a viable alternative to outsourcing, as a
      vehicle to add value, a sense of corporatism and team spirit to the organisation.

PMID- 12233017
TI  - Hereford Hospital: a 65 m Pounds PFI development project.
AB  - The new 340-bed acute general hospital at Hereford is one of a growing number of
      innovative PFI healthcare projects where Sodexho is a leading consortium member.
      The company is an equity partner with a 30-year contract to provide support
      services.

PMID- 12233018
TI  - Highly integrated system solutions for air conditioning.
AB  - Starting with the air handling unit, new features concerning energy efficient air
      treatment in combination with optimisation of required space were presented.
      Strategic concepts for the supply of one or more operating suites with a modular
      based air handling system were discussed. The operating theatre ceiling itself,
      as a major part of the whole integrated system, is no longer a simple air outlet:
      additional functions have been added in so-called media-bridges, so that it has
      changed towards a medical apparatus serving as a daily tool for the physicians
      and the operating staff. Last and not least, the servicing of the whole system
      has become an integral part of the facility management with remote access to the
      main functions and controls. The results are understood to be the basis for a
      discussion with specialists from medical and hygienic disciplines as well as with
      technically orientated people representing the hospital and building-engineering.

PMID- 12233019
TI  - Examining means of improving fire safety.
AB  - There are numerous products available to designers and architects for all areas
      of fire safety within buildings. Once the performance criteria have been set by
      the client, insurer, engineer or approving authority the options can be endless
      and generally those designers with historical experience with a particular fire
      safety product will specify these time and again. Most manufacturers of fire
      safety products produce the same types of products with variances on aesthetics
      and costs. The products mentioned above are specialised for particular
      applications, where other products may not be applicable. When choosing products
      for buildings, important areas which should also be considered are: Life
      expectancy of the product. New products may seem completely suitable to a
      particular design specification. However, if the product is fairly new, the
      expected life of the product may not be known. This should be considered as the
      client specification may be contradicted. Monopolies. Due to the nature of fire
      safety products, they are generally bespoke and specialised for certain
      applications. Therefore, there may only be one manufacturer of a product. This
      can sometimes lead to problems with clients since tender packages are the
      preferred method of assigning a particular product or system. In this case the
      performance which is being aimed for should be clearly stated and tenders also
      sent to manufacturers of similar products which closely fit this specification.

PMID- 12233020
TI  - Transformerless vs transformer-based on-line UPS.

PMID- 12233021
TI  - [Cholesterol values of an elderly person].

PMID- 12233022
TI  - [Diagnostics, therapy and prognosis of congenital heart disease in the fetus].

PMID- 12233023
TI  - [On receiving a breast cancer diagnosis].

PMID- 12233024
TI  - [Fever and nodular peritoneum in a middle-aged man].

PMID- 12233025
TI  - [An abnormal area of the palate in an infant].

PMID- 12233026
TI  - [How to develop clinical competence concerning psychiatric emergencies?].

PMID- 12233027
TI  - [Psychodynamic emergency psychiatry].

PMID- 12233028
TI  - [Crime and punishment].

PMID- 12233029
TI  - [An agitated psychotic patient].

PMID- 12233030
TI  - [Psychiatric assessment and treatment of a suicidal patient].

PMID- 12233031
TI  - [Doctor on duty, psychiatric patients and home visits].

PMID- 12233032
TI  - [Use of benzodiazepines in psychiatric emergency situations].

PMID- 12233033
TI  - [Antidepressant treatment and psychiatric emergency services].

PMID- 12233034
TI  - [A patient with substance abuse and the primary health care emergency services].

PMID- 12233035
TI  - [How to survive the task of being on duty in a psychiatric emergency unit?].

PMID- 12233036
TI  - [Is penicillin becoming old-fashioned?].

PMID- 12233037
TI  - [Antenatal corticosteroid therapy].

PMID- 12233038
TI  - [Neurological paraneoplastic syndromes].

PMID- 12233039
TI  - [Hormone therapies and ovarian cancer].

PMID- 12233040
TI  - [Nevi, sun and the risk of melanoma].

PMID- 12233041
TI  - [Asthma caused by bronchial irritation].

PMID- 12233042
TI  - [Leptospirosis--an increasingly common zoonosis].

PMID- 12233043
TI  - [Polypharmacy in an elderly person].

PMID- 12233044
TI  - [Antidepressant therapy and elderly persons].

PMID- 12233045
TI  - [Weight loss, joint pains and eczema].

PMID- 12233046
TI  - [Current treatment praxis of rheumatoid arthritis put into use].

PMID- 12233048
TI  - [Clinical staff and pediatric habilitation].

PMID- 12233047
TI  - [On the principles of osteitis treatment].

PMID- 12233049
TI  - [Clinical manifestations for early diagnosis of the patient with classical Menkes
      disease].
AB  - Early treatment reportedly prevents neurological disturbance in patients with
      Menkes disease. To promote early diagnosis, a questionnaire concerning symptoms
      during the neonatal period and at the age of 1 month was sent to the mothers of
      14 patients with Menkes disease. The height, body weight and head circumference
      were almost normal in most of the Menkes patients. At the age of one month, all
      patients had abnormal hair. The mothers noticed it in 8 cases, and in the
      remaining 6 cases, the abnormalities were confirmed by the photos at the age of
      one month. At this age, the mothers noticed weak activity in 5, jaundice in 5,
      dyspnea in 4 cases, feeding disturbance in 3, hypothermia in 2 and eczema in 2.
      These results suggest that recognizing hair abnormalities at a one-month check-up
      may provide a clue to the early diagnosis of Menkes disease.

PMID- 12233050
TI  - [Dystrophin gene analysis on 76 families with dystrophinopathy].
AB  - We report for the last 1 year and 9 months results of the molecular diagnosis of
      Duchenne (DMD) and Becker (BMD) muscular dystrophy at Kobe University. Analysis
      was done on 87 patients belonging to 76 families (66 DMD cases, 10 BMD cases). We
      first determined the presence of deletions or duplications using Southern blot
      analysis. Then analyzed small mutations (point mutations or small
      deletions/insertions) by mRNA analysis using RT-PCR and direct sequencing. 69
      mutations (89.5%) were found, 46 deletions (60.5%), 5 duplications (6.6%) and 17
      point mutations (22.4%) including 15 nonsense mutation. mRNA analysis from
      lymphocytes or muscle was useful for screening patients without a mutation
      identifiable by Southern blot analysis.

PMID- 12233051
TI  - [Measurement of the frontal and prefrontal lobe volumes in children with
      malnutrition by three dimensional magnetic resonance imaging scan].
AB  - To evaluate the effects of malnutrition in early life on the growth of the
      frontal and prefrontal lobes, we quantitatively measured the volumes of the
      frontal and prefrontal lobes by three dimensional (3-D) MRI in three children (1
      year 2 months to 2 years 5 months) with malnutrition. The 3-D MRI data were
      acquired by the fast spoiled gradient recalled (SPGR) sequence using a 1.5T MR
      imager. The frontal and prefrontal lobe volumes were measured by the volume
      measurement function of the Workstation. The data obtained were compared with
      those of 16 normal subjects (13 children aged 5 months to 14 years, and 3 adults
      aged 27 to 39 years). The volumes of the frontal and prefrontal lobes in the
      subjects were smaller compared with age matched controls. The results suggest
      that malnutrition in early life affects the growth of the frontal and prefrontal
      lobes.

PMID- 12233052
TI  - [Measurements of the frontal and prefrontal lobe volumes by three dimensional
      magnetic resonance imaging scan--III. Analysis of sex differences with advanced
      age].
AB  - To determine whether there is sex difference in the growth of the frontal and
      prefrontal lobes, we quantitatively measured the volume of these lobes by three
      dimensional (3-D) MRI in healthy 12 males (5 months to 39 years) and six females
      (1 year 11 months to 27 years). The left and right lobes were studied separately.
      The 3-D MRI data were acquired by the fast spoiled gradient recalled (SPGR)
      sequence using a 1.5T MR imager. The frontal and prefrontal lobe volumes were
      measured by the volume measurement function of the Workstation. In males, the
      left to right ratio (L/R ratio) of the frontal and prefrontal lobes increased
      with age. On the contrary, in females, L/R ratio of the frontal and prefrontal
      lobes showed no significant change with advancing age. These results highlighted
      sex-specific maturational changes of the frontal and prefrontal lobes and
      suggested that quantitative data on the frontal and prefrontal lobe are important
      in interpreting brain abnormalities in children with developmental disorders.

PMID- 12233053
TI  - [The evaluation of lateralized frontal lobe function in the patients with
      autistic or attention deficit/hyperactivity disorder].
AB  - The prefrontal lobes are involved in two functionally distinct cognitive
      selection mechanisms: processing based on internal representation, such as
      planning (context-dependent reasoning) and exploratory processing of novel
      cognitive situations (context-independent reasoning). On the basis of this
      working hypothesis, a cognitive bias task (CBT; Goldberg, 1994), designed as an
      activation procedure representing contextual reasoning, was used to explore
      developmental disorders of lateralization in the frontal lobes in autistic
      disorder and attention deficit/hyperactivity disorder (ADHD). The subjects
      included 3 patients with autistic disorder, 4 with ADHD. Ten normal right-handed
      males served as controls. In CBT, a high score indicated consistency of choice: a
      context dependent selection bias, and a low score showed independent selection
      bias. The autistic group showed a score significant lower than those in controls
      (p < 0.01). The ADHD group had also a lower score. These findings implicate a
      deficit in the development of hemispheric specialization in the symptoms of these
      developmental disorders.

PMID- 12233054
TI  - [Urolithiasis induced by combined ACTH and zonisamide treatment in a patient with
      startle induced epilepsy].
AB  - A 5-year-old boy had periodic spasms and startle-induced drop attacks. Zonisamide
      (ZNS) was partially effective for the former seizures, and propranolol for the
      latter. An add-on therapy with ACTH resulted in a transient disappearance of
      seizures and an improvement of EEG. However, the patient developed urolithiasis
      with resultant hematuria and pyelectasis during ACTH therapy. ZNS can induce
      urolithiasis by increasing urinary pH and calcium (Ca) excretion, and ACTH may
      facilitate this rare adverse effect of ZNS by further increasing the urinary Ca.
      Hydrochlorothiazide could resolve the urolithiasis by decreasing the urinary Ca
      excretion.

PMID- 12233055
TI  - [Infantile partial seizures due to temporal lesions--analysis of 4 cases].
AB  - We studied 4 cases of complex partial seizures due to temporal lesions presenting
      with benign partial epilepsy in infancy. None of them had neurologic
      abnormalities. All cases had complex partial seizures, and two had lateralizing
      signs. All cases had temporal lesions. One of them was detected only by fluid
      attenuated inversion recovery (FLAIR) imaging. Histopathologically they were
      astrocytomas (grade 2 and 3), glio neuronal hamartoma and focal cortical
      dysplasia. The present cases suggest that patient with infantile complex partial
      seizures should be carefully followed up, even after the disappearance of
      seizures, by serial MRI examination including FLAIR imaging and by clinical
      observation.

PMID- 12233056
TI  - [A case of childhood onset myoclonus epilepsy with ragged-red fibers--with
      special reference to various clinical manifestations].
AB  - There are few descriptions about the clinical course of children with myoclonus
      epilepsy with ragged-red fibers (MERRF). We reported a girl who was diagnosed as
      having MERRF at 10 years of age and developed various clinical manifestations
      including chronic respiratory failure, paralytic ileus and pancytopenia at 18
      years of age. Administration of cytochrome c worsened lactic acidosis and muscle
      weakness, while intravenous hyperalimentation with copper supplementation
      gradually improved these findings as well as pancytopenia. Cytochrome c oxidase
      is a copper dependent enzyme. Its activity is extremely low in MERRF patients. It
      was suspected that deficiency of serum copper and supplementation of cytochrome c
      worsened the clinical symptoms of our patient.

PMID- 12233057
TI  - [A case of Menkes disease with urinary bladder hemorrhage].
AB  - We report a case of Menkes disease with urinary bladder hemorrhage. Diverticulums
      were found at 1 year and 3 months of age. He had repetitive urinary tract
      infections at 2 years old and died of urinary hemorrhage at 2 years and 9 months.
      Large hematoma and diverticulum were found at necropsy. In patients with Menkes
      disease, attention should paid to urinary complications.

PMID- 12233058
TI  - [Prevention of gastroesophageal reflux in the severely disabled patients using
      pectin gel].

PMID- 12233059
TI  - [The result of questionnaire to teachers: how do they treat and think about
      eating disorders of children in a school for physically handicapped].

PMID- 12233060
TI  - [The concept, definition and diagnostic criteria of sarcoidosis].
AB  - The definition of sarcoidosis in the past international conference on sarcoidosis
      is introduced. Furthermore, the diagnostic criteria proposed by Japanese Research
      Committee for Diffuse Lung Diseases of the Japan Ministry of Welfare was
      discussed upon the problem.

PMID- 12233061
TI  - [Genetic background of sarcoidosis--special reference to HLA].
AB  - A comprehensive epidemiological study (ACCESS) recently conducted in the United
      States has recognized modest familial aggregation of sarcoidosis. Therefore,
      genetic factors, in particular human leukocyte antigens (HLAs) are believed to be
      important determinants of susceptibility to sarcoidosis. A previous case-control
      study on Japanese population has postulated that an amino acid, serine, at
      position 11 of beta subunit of HLA-DR confers susceptibility to sarcoidosis.
      Whereas, a more recent study suggests that protective HLA-DR alleles, which
      encode the DR1 and DR4 antigens, were found to share characteristic small
      hydrophobic residues at the same position. Meanwhile, the first genome scan on
      sarcoidosis has found the highest linkage score in the class III region, where
      HLA-DR genes do not exist. Complete clarification of genetic mechanisms of
      sarcoidosis awaits the precise identification of causative antigens, if any.

PMID- 12233062
TI  - [Etiology of sarcoidosis].
AB  - The cause(s) of sarcoidosis is unknown. Sarcoidosis seems to result from exposure
      of a genetically susceptible subject to a specific environmental antigen(s). From
      biopsy samples of lymph nodes from patients with sarcoidosis, Propionibacterium
      acnes has been isolated in culture, and many genomes of P.acnes or P.granulosum
      have been detected by quantitative PCR. Antigen-specific mitogenic responses of
      peripheral blood mononuclear cells were induced in sarcoidosis patients but not
      in healthy controls, when recombinant proteins from a propionibacterial trigger
      factor were used as stimulators. Sarcoidosis may arise from a Th1 immune response
      to one or more antigens of propionibacteria in an individual with a hereditary or
      acquired abnormality of the immune system.

PMID- 12233063
TI  - [Sarcoidosis--epidemiology and topics].
AB  - The incidence, clinical course, and clinical features of the disease sarcoidosis
      differ somewhat among populations and geographic regions. Pathogenically,
      sarcoidosis is characterized as antigen-driven macrophage-T cell activation
      leading to the formation of epithelioid cell granuloma. The etiological agents of
      sarcoidosis remain unknown. To clarify the etiological agents, as well as common
      disease features shared by all disease populations in all regions, numerous
      molecular studies have adopted strategies with T cell antigenic receptor,
      chemokine production, and ACE gene polymorphism. We expect trials of this type to
      produce fruitful results in the near future.

PMID- 12233064
TI  - [Epithelioid cell granuloma in sarcoidosis: light and electron microscopic
      morphology].
AB  - Light and electron microscopic features of epithelioid cell granuloma in
      sarcoidosis were presented, focusing on the lymph node and the lung which are
      mostly involved. The distribution of granulomas is frequently conglomerated with
      occasionally central necrosis. Hamazaki-Wesenberg body in lymph node is
      considered to be closely associated with Propionibacterium acnes. Granuloma is
      encircled by reticulin fibers and collagen fibers within the granuloma are
      detected in electron microscopy. Granuloma may disappear but some develop
      hyalinization and fibrosis associated with lymphatic and vascular involvement and
      specific organ structure. Vascular endothelial growth factor is
      immunohistochemically demonstrated in granuloma, which may be related to
      microvascular dilatation and proliferation. Thus, epithelioid cell granulomas
      play an central role in fibrosis and microangiopathy in sarcoidosis.

PMID- 12233065
TI  - [Origin of epithelioid cells in sarcoid granuloma].
AB  - Sarcoid epithelioid cells are believed to be a variant of tissue macrophages,
      which are derived from circulating monocytes in blood. Formation of monocytes and
      macrophages are controlled by hematopoietic growth factors, i.e.; colony
      stimulating factors in the bone marrow. In the presence of colony-stimulating
      factors and/or vitamin D3, blood monocytes can proliferate and differentiate into
      epithelioid cells and multinucleated giant cells. Recent observations that
      sarcoid granulomas themselves produce colony-stimulating factors and vitamin D3
      suggest vitamin D3 and colony-stimulating factors produced by sarcoid granulomas
      stimulate the proliferation and differentiation of circulating monocytes into
      macrophage-epithelioid cells, which form new sarcoid granulomas.

PMID- 12233066
TI  - [Characterization of distribution of immunological competent cells in sarcoid
      granuloma].
AB  - Sarcoidosis is a systemic, immunological disorder that is histologically defined
      the presence of noncaseating granuloma in the involved tissue. Granuloma
      formation follows the accumulation of large numbers of T lymphocytes within the
      lesions. To elucidate the immunopathologic situation of granuloma-formation in
      sarcoidosis, the relationship between activated T lymphocyte subsets including Th
      1 and Th-2 cells has been studied by using immunohistochemical, RT-TCR, and in
      situ hybridization techniques for functional T cell subsets and by using RT-PCR
      SSCP analysis for T cell clonotypes. The results of analysis of functional T cell
      subsets showed that T cells in internal area (core) of granulomas were
      predominantly Th-2 subset. On the other hand, Th-1 cells were present in
      abundance in the surrounding areas(rind). The additional results showed the
      presence of common T-cell clones in samples from different tissues, supporting
      the underlying Ag-specific mechanism in pathogenesis of sarcoidosis.

PMID- 12233068
TI  - [Clinical features and diagnostic approach of sarcoidosis].
AB  - Sarcoidosis is a multisystem disorder of unknown thiology. Patients with
      sarcoidosis present a variety of manifestations. The clinical feature of this
      disorder depends on age, gender and ethnicity of the patients, duration and
      activity of the illness, site and extent of organ involvement. In Japanese
      patients, ocular lesions as in prevalence cases showed a marked increase in
      recent years, while the proportion of patients with BHL or pulmonary involvement
      detected by chest X-ray mass survey was decreasing. Of symptoms at presentation,
      ocular symptom is most frequent and the following symptoms are skin
      manifestation, cough, general fatigue, fever and so on. Patients without symptoms
      at presentation are estimated as a quarter of patients. The diagnosis of
      sarcoidosis needs a compatible clinical feature and histologic demonstration of
      noncaseating granulomas. Additionally, other diseases presenting similar clinical
      pictures and/or pathologic findings should be excluded. In order to obtain a
      histologic confirmation of the disease and to assess extent, severity and
      activity of the disease, the further examinations for diagnostic work-up in
      patients with sarcoidosis are required after establishing clinical and
      radiological features.

PMID- 12233067
TI  - [Mechanism of sarcoid granuloma formation--participation of cytokines and
      chemokines].
AB  - In sarcoidosis, unknown antigen(s) causes Th1-mediated granulomatous inflammation
      with cytokines such as IFN gamma and IL-12, initially. IL-16, IL-8, IP-10 and
      RANTES are participated in the accumulation of CD4+ T cell. For the chemotaxis of
      macrophages and monocytes, MCP-1, MIP1-alpha and RANTES are participated. Local
      proliferation of T cell is induced by IL-2 and IL-15 and that of
      macrophage/monocyte lineage is done by M-CSF, GM-CSF and G-CSF. Removal of the
      causative antigen(s) allows immune-suppressive cytokines such as TGF beta to
      downregulate the immune response and granuloma formation. Failure of removal of
      causative antigen(s) can induce prolonged existence of granuloma and irreversible
      fibrosis.

PMID- 12233069
TI  - [Role of biochemical markers in sarcoidosis].
AB  - Sarcoidosis is a systemic granulomatous disease that affects various organs.
      However, its pathogenesis has not yet been fully understood. Biochemical markers
      in sarcoidosis appears to be closely related to the immunological events and the
      activity of inflammatory effector cells at sites of granuloma. These markers,
      therefore, have been expected to reflect the disease activity and/or to predict
      prognosis. Although some markers are helpful tools as diagnostic aids and disease
      activity markers, no single marker allows definitive diagnosis of sarcoidosis or
      may accurately predict the disease prognosis. Among numerous biochemical markers
      reported previously, only angiotensin converting enzyme (ACE) serum level has
      gained a proven value in the clinical field. Further studies are required to
      identify more useful biochemical markers, which allow definitive diagnosis or
      predict the disease activity and prognosis in sarcoidosis.

PMID- 12233070
TI  - [Roentgenographic type and CT findings in pulmonary sarcoidosis].
AB  - There are five roentgenographic type of intratracic changes, Type 0 means no
      visible intratracic findings. Type I is bilateral hilar lymphadenopathy, Type II
      is bilateral hilar adenopathy accompanied by parenchymal infiltration. Type III
      is only parenchymal infiltration and type IV is advanced fibrosis. CT findings
      are peribroncho-vascular markings, diffuse small nodules, and large irregular
      nodules. Usually diffuse small nodules had tendency to improve, although
      peribronchial markings, atelectacis, pleural thickening, and bullae are
      irreversible and progressive. CT plays an important role in the diagnosis and
      prognostic value in pulmonary sarcoidosis.

PMID- 12233071
TI  - [67Gallium whole body scintigraphy and single photon emission computed
      tomography(SPECT) in sarcoidosis].
AB  - 67Gallium scintigraphy has been used for years in sarcoidosis as a makers of
      activity, a determiner of the extent and distribution of the disease and an aid
      in therapeutic management. However, it is currently used mainly to assist in
      diagnosis in difficult cases, particularly in those with isolated extrathoracic
      sarcoidosis. The finding of the typical lambda or panda sign supports the
      diagnosis and reinforces the indication to perform an appropriate biopsy. In
      addition, the detection of clinical silent extrathoracic uptake may provide sites
      for biopsy. The importance of gallium scintigraphy lies in the possibility of
      whole-body screening for inflammation localizations, particularly when physical,
      laboratory, lung function and radiographic examinations fail to provide
      convincing evidence of active sarcoidosis. Furthermore, it can be helpful in the
      follow-up of the effect of supportive treatment. 18F-FDG PET is based on the
      increase of glucose metabolism in inflamed tissues. It may have great potential
      to assess sarcoidosis activity, but it is still largely experimental and is not
      routinely employed.

PMID- 12233072
TI  - [Histologic diagnosis of sarcoidosis].
AB  - In Japan, elderly patients with sarcoidosis, cardiac sarcoidosis and severe
      pulmonary sarcoidosis patients have been increased. The patients with ocular
      manifestations without intrathoracic involvement have been also increased and it
      is, however, difficult to establish the diagnosis and to confirm such patients as
      sarcoidosis. To detect the histological findings such as epithelioid cell
      granuloma is gold standard in diagnosis. Transbronchial lung biopsy, scalene node
      biopsy, muscle biopsy and video-assisted thoracoscopic surgery are useful
      procedure for getting the tissue samples. We performed TBLB in 655 patients with
      clinical features of sarcoidosis. In 125 out of 293 patients with stage 0, 229
      out of 272 with stage I, 66 out of 70 with stage II and 19 out of 20 with stage
      III patients, epithelioid cell granuloma was found. The effort to getting proper
      tissue samples of suspected sarcoidosis is important.

PMID- 12233073
TI  - [Bronchoalveolar lavage in sarcoidosis].
AB  - A characteristic feature of BAL in patients with sarcoidosis is an increase of
      the total cell number, lymphocytes percent, or CD4/CD8 ratio of T lymphocytes.
      With respect to T lymphocytes, sarcoidosis has been recognized as a granulomatous
      disease characterized by dominant expression of Th1 cytokines. Recently Th1
      cytokine profile in both CD4+ and CD8+ T lymphocytes in BAL fluid were
      demonstrated at the single-cell level. Furthermore, alveolar macrophages
      collected from BAL fluid were also investigated. Increased expression of 25
      hydroxyvitamin D3 1 alpha-hydroxylase with mRNA level in alveolar macrophage were
      revealed in active sarcoidosis. Previously we showed that the B allele of the
      vitamin D receptor gene polymorphism may be regarded as a risk factor in the
      onset of sarcoidosis. The metabolism of vitamin D may be related to granuloma
      formation.

PMID- 12233074
TI  - [Vasculitis and collagenous-vascular involvement in association with
      sarcoidosis].
AB  - Sarcoidosis is a systemic granulomatous disorder of unknown origin. It unusually
      complicates systemic vascular involvement. We concisely review clinico
      pathological findings of vascular involvement, including granulomatous angitis
      and microangiopathy. The clinical features of sarcoidosis may mimic those of many
      rheumatic disorders and sarcoidosis may coexist with autoimmune diseases. We
      review both rheumatologic manifestations, including bone, joint, and muscle of
      sarcoidosis and immunological findings of autoimmune diseases complicated with
      sarcoidosis, including 2-case reports of Sjogren's syndrome and
      dermatomyositis/polymyositis.

PMID- 12233075
TI  - [Hypercalcemia in sarcoidosis].
AB  - Although hypercalcemia has long been recognized as a complication of sarcoidosis,
      the incidence of hypercalcemia (> or = 11 mg/dl) in Japan is probably less than
      5%. 1 alpha, 25(OH)2D3 is the main cause for hypercalcemia in sarcoidosis and
      overproduced by sarcoid granulomata. Gamma-interferon produced by activated
      lymphocytes and macrophages plays a major role in the synthesis of 1 alpha,
      25(OH)2D3. PTH release is down regulated by high serum concentration of 1 alpha,
      25(OH)2D3. Parathyroid hormone related protein may also contribute to the
      hypercalcemia of sarcoidosis. Treatment of hypercalcemia and hypercalciuria
      consists of a low calcium diet, adequate hydration, minimization of exposure to
      sunlight and reducing overproduction of 1 alpha, 25(OH)2D3. Prednisone, 15 to 25
      mg/day, is the drug of choice to reduce the overproduction of 1 alpha, 25(OH)2D3.

PMID- 12233076
TI  - [Neurosarcoidosis].
AB  - Sarcoidosis is a chronic systemic disease of unknown causes characterized by
      noncauseating granuloma in various organs. Neurological involvement occurs in 5
      6% of patients with sarcoidosis. Most patients with neurosarcoidosis have
      extraneurologic abnormalities and extraneurologic biopsies usually support the
      diagnosis, however, nearly half of the patients with neurosarcoidosis present
      with neurological manifestations without systemic symptoms. Several cases of
      isolated neurosarcoidosis have been reported, making the diagnosis difficult.
      Although several diagnostic criteria have been proposed, neuropathological
      examination is required for the definite diagnosis. Brain biopsy may still be
      required in selected patients. Since it is often difficult to perform, clinical
      assessment with various combinations of modern neuroimaging techniques is
      important. Lumbar puncture is useful to rule out other diseases but CSF changes
      are not specific. Elevated serum ACE level is also not a specific diagnosis test.
      Any part of the CNS can be involved, but there is predilection for hypothalamus,
      pituitary gland, leptomeninges, and cranial nerves particularly facial nerve.
      Although corticosteroids are the main stay of therapy, refractory cases can be
      treated by immunosuppressive and radiation therapy.

PMID- 12233077
TI  - [Cardiac sarcoidosis].
AB  - Cardiac sarcoidosis induces heart failure death or sudden death in many cases and
      is thus often associated with a poor prognosis. In Japan 47-78% of sarcoidosis
      patients die of cardiac lesions. Early diagnosis is important in such cases, and
      a comprehensive judgment based on the endomyocardial biopsy, echocardiography and
      nuclear medicine examination findings should be made according to the 'Handbook
      of the Diagnosis of Cardiac Sarcoidosis'. Once a diagnosis is made the
      introduction of steroid therapy should be considered. Steroid administration
      should be conducted referring to the 'Guidelines to the Treatment of Cardiac
      Sarcoidosis'.

PMID- 12233078
TI  - [Cutaneous sarcoidosis].
AB  - The frequency of skin involvement of sarcoidosis is 10-30% of all cases, but the
      prevalence of a particular type of cutaneous lesion varies among races as well as
      individual cases. Cutaneous involvement is divided into specific and nonspecific
      categories. Specific lesions include nodules, plaques, lupus pernio, subcutaneous
      nodules, and other rare manifestations as well as scar infiltrates. Despite the
      clinical importance of scar infiltrates in the diagnosis of sarcoidosis, it is
      often overlooked because the lesions are usually small and asymptomatic. There is
      some clinical importance of cutaneous sarcoidosis; the ease in obtaining lesional
      samples which enables a histological diagnosis of sarcoidosis, and the
      association of a particular type of cutaneous lesion with other organ
      involvement.

PMID- 12233079
TI  - [Ocular sarcoidosis].
AB  - Ocular involvement of sarcoidosis is frequent, and it is often the initial
      clinical manifestation of the disease. The most common ocular lesions include
      granulomatous uveitis associated with iris and trabecular nodules, string of
      pearl-type vitreous opacities, retinal paerivasculitis mainly affecting veins,
      and patchy retino-choroidal exudates. A half of the patients with typical ocular
      lesions suggestive of sarcoidosis did not show the systemic evidence, and they
      remained as sarcoidosis suspects. Risks of visual deterioration are secondary
      glaucoma, vitreous opacities, cystoid macular edema, and retinal
      neovascularization. Thirty-four % of the patients were treated with systemic
      corticosteroids, and some patients required other treatment such as methotraxate.
      Twenty-one% of the patients resulted in the poor visual acuity of less that 0.5.

PMID- 12233080
TI  - [Sarcoidosis of the head and neck].
AB  - Sarcoidosis is a systemic granulomatous disorder characterized varying degrees of
      involvement of the skin, viscera, and lymph nodes by non-caseating granulomata.
      Otolaryngologic manifestations of sarcoidosis are seen in about 10% of patients
      with sarcoidosis; neck mass, followed by parotid swelling and reversible facial
      nerve palsy are most common. Hearing loss and peripheral vestibulopathy are rare,
      and are incompletely understood. Nasal sarcoidosis shows nasal obstruction,
      rhinorrhea and nasal bleeding, and nasal mucosa of the patients has small sarcoid
      nodules in the endoscopic findings. The otorhinolaryngologist is critical to the
      diagnosis, because of the ease of biopsy in most cases of sarcoidosis in the head
      and neck. Steroids are central to treatment.

PMID- 12233081
TI  - [Breast sarcoidosis].
AB  - Sarcoidosis is a multisystem disorder of unknown etiology characterized
      histologically by the presence of noncaseating epithelioid cell granuloma.
      Extrapulmonary organs most commonly affected are the lymph nodes and the skin.
      Sarcoid involvement of the breast is extremely rare but when present it may be
      confused with a malignant neoplasm clinically. A review of literature disclosed
      29 cases of breast sarcoidosis. In seventeen cases(61%) a breast tumor was first
      manifestation of systemic sarcoidosis. Three cases were co-exist with breast
      cancer. All but one cases were required excisional biopsy. We discuss some
      diagnostic problems such as sarcoid-like reaction briefly.

PMID- 12233082
TI  - [Heerfordt syndrome].
AB  - The Heerfordt syndrome is characterized by fever, uveitis, swelling of parotid
      gland and facial nerve palsy, and 53 cases have been reported in Japan until
      2000. In the present review, we mainly focused on those clinical cases reported.
      Most patients were between 20 and 40 years of age, and females appeared to have
      greater risk than males. The definite diagnosis of this syndrome is established
      histologically according to sarcoidosis. In addition 67 gallium scan is helpful
      for diagnosis, and it shows increased uptake of Ga to the ophthal lesion, parotid
      glands and hilar lesions. Therapeutic trial with prednisolone is sometimes
      required especially for facial palsy.

PMID- 12233083
TI  - [Corticosteroid therapy for sarcoidosis].
AB  - Even after 50-year experience of corticosteroid therapy for sarcoidosis, no
      definite protocol nor indication criteria have been established for the treatment
      of sarcoidosis. The high incidence of spontaneous remission, the high rate of
      relapse after steroid-induced remission, absence of sensitive marker to predict
      the disease progression, lack of evidences whether corticosteroids alter the
      natural history of sarcoidosis, and the adverse effects of long-term
      corticosteroid therapy have made the indication controversial. As a consensus
      statement at present, the most common indication of systemic corticosteroid
      therapy for sarcoidosis is systemic and symptomatic diseases including cardiac
      disease, neurologic disease, eye disease refractory to topical therapy, and
      hypercalcemia, as well as the progressive pulmonary disease.

PMID- 12233084
TI  - [Non-steroid therapy for sarcoidosis].
AB  - Sarcoidosis is a systemic granulomatous disease that the epidemiology remains
      unknown. The appropriate therapy for sarcoidosis also has not been well defined.
      Systemic therapy is clearly indicated for cardiac disease, neurologic disease,
      eye disease without response to topical therapy, hypercalcemia, and progressive
      symptomatic disease. Corticosteroid are very commonly used as systemic therapy
      for sarcoidosis. However, there are some patients who can not be controlled with
      corticosteroid alone and/or have adverse reactions to corticosteroid. Several
      cytotoxic agents, including methotrexate, azathioprine, cyclophosphamide,
      chlorambucil and cyclosporine A, have been used to treat sarcoidosis. There are
      no studies that have clearly concluded when these agents should be used for
      treatment. On the basis of safety and efficacy, methotrexate and azathioprine are
      the preferred drugs. The antimalarial agents, including chloroquine and
      hydroxychloroquine, most often used to treat sarcoidosis.

PMID- 12233085
TI  - [Prognosis and prognostic factors of sarcoidosis in Japan].
AB  - Sarcoidosis is a systemic granulomatous disease that primarily affects the lung
      and lymphatic systems. Sarcoidosis patients commonly have spontaneous remission
      and good prognosis. But some patients show chronic, progressive and life
      threatening conditions. Determination of prognosis based on the initial clinical
      presentation is important for the treatment. In this article, we review natural
      history, prognosis and the factors related prognosis of sarcoidosis patients in
      Japan. Shadows on chest radiograph were cleared in 76% of patients for 10 years.
      Approximately 15% of patients had severe organ dysfunction. In 60% of the
      sarcoidosis autopsy cases, the causes of death were attributed to organ
      involvement of sarcoidosis. Adverse prognostic factors are advanced age at onset,
      the presence of symptoms, extrathoracic involvement and treatment of
      corticosteroids.

PMID- 12233086
TI  - [The latest review of therapeutic angiogenesis using angiogenic growth factors to
      peripheral arterial diseases].
AB  - Therapeutic angiogenesis using angiogenic growth factors is expected to be a new
      treatment of patients with severe ischemic diseases. Indeed, human gene therapy
      for peripheral arterial disease(PAD) using VEGF gene demonstrated the beneficial
      effects. In contrast, we have reported the potent angiogenic activity of
      hepatocyte growth factor (HGF) in animal study and we planned gene therapy for
      ASO and Buerger disease using HGF gene (TREAT-HGF). In a prospective, open
      labeled clinical trial, we investigated the safety and biological efficiency of
      this gene therapy in patients with peripheral arterial disease(PAD) who had
      failed conventional therapy.

PMID- 12233087
TI  - [How I do it: partially thrombosed giant carotid-posterior communicating
      aneurysm].

PMID- 12233088
TI  - [Cerebrovascular disease (1): intracerebral hemorrhage, no. 3 in series of
      articles: basic knowledge of neuropathology for neurosurgeons].

PMID- 12233089
TI  - [Problems and proposals from neurosurgical practice, no. 6 in series of articles:
      controversy and reform proposals concerning insured medical care in
      neurosurgery].

PMID- 12233090
TI  - [Operative approaches to tumors in and around the anterior half of the third
      ventricle].

PMID- 12233091
TI  - [Recurrence of intracranial germinoma initially treated with chemotherapy only].
AB  - Irradiation for intracranial germinoma may be associated with significant
      neuroendocrinological sequelae, so the establishment of lower effective doses of
      radiation is desirable. Eight consecutive patients with intracranial germinoma
      underwent combination chemotherapy with BEP (bleomycin, etoposide, and cisplatin)
      or PE (cisplatin and etoposide) without irradiation between 1996 and 1997. The
      diagnosis was based on endoscopic or stereotactic biopsy, or transsphenoidal
      surgery in 7 cases. These 7 patients obtained complete response (CR) after
      treatment with chemotherapy only. The diagnosis of pure germinoma was based on
      neuroradiographic appearances and the normal levels of tumor markers in patients
      with suprasellar and pineal-region germ cell tumors. Although all patients
      obtained CR, 5 patients relapsed at a mean period of 19 months after the initial
      therapy. The mean follow-up period was 53 months. Two of these 5 patients had
      recurrence around the ventricle wall. Additional chemotherapy and total ventricle
      irradiation (24 Gy) achieved CR, but delayed seeding in the optic nerves outside
      the irradiated field was detected. One patient suffered peritoneal dissemination
      via a ventriculoperitoneal shunt with intracranial dissemination. Another patient
      obtained CR after PE therapy, but there was not histological verification.
      However, 35 months after the initial therapy, surgical extirpation of the
      recurrent tumor revealed immature teratoma. One patient refused treatment for
      recurrence at the initial tumor site and died 42 months after the initial
      treatment. Adequate initial therapy is absolutely essential for the treatment of
      intracranial germinoma. The chemotherapy regimens in use today cannot be
      recommended as initial therapy without irradiation because of the high recurrence
      rates.

PMID- 12233092
TI  - [Gamma knife radiosurgery for spontaneous carotid-cavernous sinus fistula (CCF)].
AB  - Gamma knife radiosurgery was carried out for spontaneous CCF (carotid-cavernous
      sinus fistula) in 8 patients (1 male and 7 females), and its results were
      reported. The ages ranged from 48 to 74 years with a mean of 60.6 years. As
      initial treatment before radiosurgery, embolization was carried out except in one
      patient, and radiotherapy was used in two patients. Six patients were in the
      category of Barrow's type D, and two patients were in the category of Barrow's
      type B. As it contained the fistula, the lateral wall of the cavernous sinus was
      irradiated with 8-14.5 Gy (mean 10.8 Gy). As a result, complete obliteration of
      CCF was confirmed by DSA in seven of the eight patients between 6 and 18 months
      after radiosurgery. There were no side effects observed during a follow-up period
      of 8 to 116 months. Although the main treatment for spontaneous CCF is
      intravascular surgery at present, gamma knife radiosurgery is a useful adjuvant
      treatment for the residual CCF after embolization.

PMID- 12233093
TI  - [Associated meningioma and neurofibroma at the same cervical level without
      clinical signs of neurofibromatosis: case report].
AB  - A 59-year-old woman presented with a history of progressive clumsiness and
      numbness in both hands. MRI suggested a solid mass extending, from the intradural
      extramedullary, extradurally at the left C1/2 level. However, intraoperative
      findings revealed the both the intradural tumor and the extradural tumor existed
      separately. Histopathological findings revealed coincident meningioma
      (intradural) and neurofibroma (extradural). These lesions were not associated
      with neurofibromatosis, and the patient did not have other tumors in either the
      brain or at other levels of the spine. The occurrence of different types of
      spinal tumors without clinical signs of neurofibromatosis is very rare. Only five
      cases have been reported in the literature. To our knowledge, this is the first
      case of occurrence of different types of spinal tumors at the same level.

PMID- 12233094
TI  - [Two cases of symptomatic arachnoid cysts in elderly patients--a comparison and
      analysis with child cases].
AB  - A symptomatic arachnoid cyst in an elderly patient is rare. We report two cases
      of symptomatic arachnoid cysts in elderly patients. The first case is that of a
      73-year-old woman complaining of headache and speech disturbance. She had an
      arachnoid cyst in the left interhemispheric fissure. This is rare. Only two
      interhemispheric arachnoid cysts in the elderly have ever been reported. The
      other case is that of a 64-year-old woman, having right hemiparesis and dementia
      and a cyst is shown in her left temporal lobe. Both patients underwent a
      cystectomy which resulted in the disappearance of their symptoms. Only 56 cases
      of symptomatic arachnoid cyst over the age of 60 years have ever been reported.
      We made an analysis of 58 cases, including our two cases, and compared it with
      child cases. In cases of the elderly, the symptoms are usually headache,
      hemiparesis, gait disturbance and dementia, which are similar to symptoms of
      chronic subdural hematoma and normal pressure hydrocephalus. On the other hand,
      child cases usually reveal signs of intracranial hypertension. Several authors
      have reported their therapeutic method for child symptomatic arachnoid cysts.
      However, it is difficult to determine the best method for treating child cases at
      this time. We think a cystectomy is the first choice of operative procedure for
      symptomatic arachnoid cyst in the elderly.

PMID- 12233095
TI  - [Congenital dermal sinus tract of recurrent pyrexia: case report].
AB  - The authors present a case of congenital dermal sinus tract with epidermoid
      tumor. This 1-year-old boy was referred to the pediatric service of another
      hospital with recurrent pyrexia of unknown origin in April, 1999. The
      pediatrician found two dimples, pigmentation, and coarse hairs on the midline in
      his sacral region. Computerized tomography (CT) scans revealed a spina bifida
      below the S1 level. Magnetic resonance (MR) imaging revealed a dermal sinus tract
      in the cranial direction to a cystic tumor at L2-4 levels. He was transferred to
      our hospital, and the tract and tumor were totally removed in June, 1999. The
      histological findings and Escherichia coli in the smear culture of the tumor
      contents identified it as an infected congenital dermal sinus tract with
      epidermoid tumor. The patient received antibiotics for two weeks after surgery
      and there was no clinical or radiographic recurrence of either infection or
      tumor. The authors propose early diagnosis and radical treatment, because
      infected congenital dermal sinus tract often leads to a bad neurological
      prognosis.

PMID- 12233096
TI  - [Third ventricular chordoid glioma: report of a surgical case].
AB  - We reported a rare case of third ventricular chordoid glioma and reviewed the
      literature. A 25-year-old male presented with a two-year history of voracious
      appetite. Three months prior to admission, he developed progressive memory
      impairment. CT scan showed a well circumscribed, slightly hyperdense mass without
      calcification in the third ventricle. The 4.5-cm oval mass occupying the anterior
      part of the third ventricle was homogeniously enhanced on MR images after
      administration of contrast medium. Small cystic components were present in the
      periphery of the mass. CT-guided stereotactic biopsy was performed.
      Microscopically, epithelioid tumor cells were embedded in mucinous stroma
      containing a lympho-plasmacytic infiltration. The tumor cells were immunoreactive
      for GFAP and vimentin. The MIB-1-positive rate was 1.2%. The histological
      diagnosis was a chordoid glioma. One month after the biopsy, a right frontal
      craniotomy was performed to remove the tumor via the anterior transcallosal
      interfornitial approach. The tumor arising from the anterior part of the third
      ventricle wall was soft, mildly vascular and light-grayish. The tumor was
      completely resected. The histological findings were identical with those of the
      biopsy specimens. Postoperatively, the patient developed diabetes inspidus,
      hyperthermia, worsening memory impairment, and transient hyponatremia. The
      patient's symptoms gradually improved and follow-up MR images showed no evidence
      of recurrent tumor 17 months after the resection. Despite low-grade appearance,
      attachment of the tumor to the hypothalamus preclude complete resection, and this
      may result in tumor recurrence and less favorable prognosis in the current
      reports. Early detection and aggressive resection followed by stereotactic
      radiotherapy are important in the management of chordoid glioma.

PMID- 12233097
TI  - [A case of dural arteriovenous fistula of the inferior petrosal sinus
      successfully treated by transarterial and transvenous embolizations].
AB  - A 69-year-old male was admitted with chemosis and exophthalmos of his right eye.
      Angiograms revealed a dural arteriovenous fistula (AVF) involving the right
      inferior petrosal sinus. The AVF was fed by the right occipital and ascending
      pharyngeal arteries and drained into the cavernous sinus and right superior
      ophthalmic vein from the right inferior petrosal sinus. He was treated by
      transarterial embolization with polyvinyl alcohol in order to reduce the shunt
      flow through the fistula. Then he was treated by transvenous embolization with
      GDC coils five days after the arterial embolization. Symptoms in his right eye
      have completely disappeared. Transvenous embolization combined with transarterial
      embolization is a useful and safe approach in the management of AVF involving the
      inferior petrosal sinus.

PMID- 12233098
TI  - [Atlas burst fracture (Jefferson fracture) requiring surgical treatment after
      conservative treatment--report of two cases].
AB  - Most cases of atlas burst fracture do not require surgical stabilization, because
      they can be successfully treated with external immobilization. The authors
      present two cases of atlas burst fracture in which surgical stabilization was
      required after external immobilization. The first patient was a 50-year-old male
      and the second patient was a 34-year-old male. Both presented with neck pain
      without neurological symptoms after a traffic accident. Neuroradiological
      examinations revealed atlas burst fracture in both patients. They were initially
      treated with conservative treatment; one with a rigid collar and the other with a
      halo vest. However, lateral offset of the atlas on the axis increased and atlanto
      axial instability became evident three months later in both patients. They
      underwent upper cervical arthrodesis with satisfactory results. The authors
      review surgical indication and its timing in patients with atlas burst fracture.

PMID- 12233099
TI  - [Serial magnetic resonance angiography in a case with isolated angiitis of the
      CNS].
AB  - Isolated angiitis of the central nervous system (IAC) is an idiopathic type of
      vasculitis, exclusively affecting small to medium-sized blood vessels of the
      central nervous system. We report serial angiographical findings, mainly
      demonstrated with magnetic resonance angiography (MRA) in a case of IAC. A 58
      year-old-female came to our hospital because of a sudden headache. Computed
      tomography (CT) did not show any particular findings. MRA 3 days after the onset
      revealed diffuse arterial dilatations and segmental stenoses of the middle and
      anterior cerebral arteries. However, these findings did not lead us to make a
      diagnosis of IAC. Two days later she was admitted with increased headache and
      subcortical hemorrhage in the left frontal lobe on CT. Subsequent MRA
      demonstrated remarkable changes such as dilatated main trunks with segmental
      stenoses. Steroid pulse therapy was started after definite diagnosis of IAC. She
      improved gradually and was headache-free 15 days after the onset. Nevertheless,
      follow-up MRA at 15 days revealed diffusely narrowed anterior and middle cerebral
      arteries with multiple segmental stenoses. Characteristic findings of angiitis
      showed improvement at 29 days and had disappeared at 73 days. The patient
      discontinued corticosteroids and has remained free from headache for the last 7
      months.

PMID- 12233100
TI  - [Coronary artery bypass grafting in octogenarian].
AB  - Coronary artery bypass graftings (CABG) in elderly patients are increasing in
      recent years. Several studies have shown that the rate of complications and
      mortality is higher in elderly patients than in younger ones. This report
      presents results of CABG in octogenarians. From January 1996 to December 1999,
      362 patients underwent isolated CABG, of whom 15 were over 80 years old (80-year
      group) and 122 were 70-79 years old (70-year group). Preoperative cardiac
      function was worse in the 80-year group than in 70-year group [60% vs 29% in
      Canadian Cardiovascular Society (CCS) class III or IV]. No significant difference
      was found between two groups in extracorporeal circulation time, aortic clamp
      time, the number of bypasses and postoperative complications. We conclude that
      CABG should not be excluded in octogenarians because of their chronological age
      alone.

PMID- 12233101
TI  - [Postintubation tracheal stenosis; problems associated with choice of
      management].
AB  - We experienced a case with tracheal stenosis due to postintubation damage, or so
      called cuff stenosis. A 50-year-old man who attempted suicide by pounding nails
      into his head and chest using carpenter's tools was treated by endotracheal
      intubation and immediately underwent emergency surgery in July 2000. The patient
      was placed on artificial ventilation with oral endotracheal intubation, and a
      tracheostomy was performed 4 days after the operation. After that, his
      respiration recovered and he was weaned from the respirator. He was discharged 22
      days after surgery with no respiratory symptoms. Two days after discharge, he
      complained of wheezing and dyspnea. Medical examination revealed that the
      cervical trachea had a severe circumferential stenosis 2.5 cm from the second
      tracheal cartilage. On retrospective inspection, the region of stenosis was
      compatible with the cuff site of the endotracheal tube used for the emergency
      operation. At first we tried nonoperative treatment, considering his mental
      state. However, we found that surgical treatment was ultimately necessary. A 2.5
      cm sleeve resection of the trachea (5 tracheal cartilage rings) was performed,
      followed by end-to-end suture using 21 stitches with 4-0 MEDIFIT C thread.
      Pathologically, the surgical specimen showed degeneration and necrosis of
      tracheal cartilage with excessive growth of granulation tissue. These findings
      revealed that the etiologic basis of the tracheal stenosis was attributed to
      pressure necrosis by the cuff. The postoperative course was uneventful. Sixteen
      months after the surgery, the granulation tissue had not recurred, and
      problematic stenosis was not visible in the trachea. In this report, we discussed
      a reasonable management of postintubation tracheal stenosis. Tracheoplasty has
      been proposed as the most reliable method for treating tracheal stenosis.
      However, the best treatment in each case is still somewhat controversial because
      various nonoperative treatment methods are recently available, including laser
      phototherapy, argon plasma coagulation, mechanical dilatation, stent replacement,
      and drug treatment. Therefore, it is very important to judge properly the
      absolute indication for surgical treatment. If granulations are removed
      successfully by the above-described nonoperative methods, attempts at repair lead
      only to regrowth of granulation tissue as long as there is necrotic tracheal
      cartilage. Thus, the determinant of treatment methods is whether postintubation
      damage extends to tracheal cartilage or not. For now, there is no accurate
      diagnostic study for viability of cartilage preoperatively. In the literature,
      symptoms due to airway stenosis occurred rapidly within one month in the case of
      patients with necrosis of tracheal cartilage. We concluded that the period
      between extubation and development of symptoms is very informative in the
      management of postintubation tracheal stenosis. Surgical approaches should be
      selected for a patient with a rapid and progressive course after extubation when
      the patient can tolerate it.

PMID- 12233102
TI  - [Coronary sinus atrial septal defect diagnosed by cyanosis after operation of
      ventricular septal defect].
AB  - We have experienced a case of coronary sinus atrial septal defect (ASD) with
      ventricular septal defect (VSD). Cardiac catheterization revealed a step-up of
      oxygen saturation in right ventricle, L-R shunt 70.3%, R-L shunt 6.9% and
      pulmonary hypertension (PH). Since diagnosis of coronary sinus ASD was difficult,
      the operation was performed under diagnosis of VSD. Although the operation was
      success, cyanosis appeared after the operation. Contrast echocardiography using
      subcostal 4 chamber view showed coronary sinus ASD with a large Thebesian valve
      and the right-to-left shunt of the ASD. The Thebesian valve seemed to lead the
      venous return flow to the left atrium. Coronary sinus ASD was closed using a
      Xenomedica patch.

PMID- 12233103
TI  - [Angiosarcoma arised from a solitary schwannoma of the chest wall].
AB  - Angiosarcomas rarely develop within a peripheral nerve or a peripheral nerve
      sheath tumor. A 68-year-old woman was admitted for right hemothorax. She had
      suffered from the left thoracic empyema and the right chest wall tumor which had
      been regarded as schwannoma clinically. Anemia got serious due to continuous
      bloody effusion. Although bleeding point was not detected by thoracotomy. The
      right chest wall tumor was resected. Postoperatively bloody effusion still
      drained continuously, she died ten days after the operation. Resected tumor was
      almost necrotized. The tumor was diagnosed as angiosarcoma pathologically, in
      which a part of schwannoma component resided. It is indicated that angiosarcoma
      in this case arised from degenerated schwannoma. It is necessary to consider
      angiosarcoma, rarely arised from degenerated schwannoma, during conservative,
      long-term observation on the care of schwannoma.

PMID- 12233104
TI  - [Comparison of the prothrombin levels between the patients with atrial
      fibrillation and patients with cardiac pacemaker implantation due to sick sinus
      syndrome during anticoagulation therapy with warfarin].
AB  - We measured the fully carboxylated prothrombin levels using the Carinactivase-1
      (CA-1) test and thus compared prothrombin levels between patients having atrial
      fibrillation (Af) without pacemaking and those having sick sinus syndrome due to
      Af with cardiac pacemaker implantation during anticoagulation therapy with
      warfarin. Total plasma samples were assayed for the CA-1 test, the prothrombin
      time international normalized ratio (PT-INR) and the thrombotest (TT). This
      prospective randomized study was carried out on 641 samples obtained at the
      Fukuoka University Hospital Department of Cardiovascular Surgery between May 1997
      and March 1999. The patients were divided into 2 groups consisting of: group A;
      144 patients having sick sinus syndrome due to Af implanted with a cardiac
      pacemaker who were treated with warfarin, group B; 497 patients atrial
      fibrillation without pacemaking who were treated with warfarin. The prothrombin
      levels in each group were 65.5 +/- 25.2 and 76.1 +/- 47.7 micrograms/ml,
      respectively. The normal prothrombin levels of group A decreased more
      significantly than in group B. Therefore, the PT-INR and TT were not
      significantly different between groups A and B. The dose of warfarin in each
      group was 2.4 +/- 1.0 and 2.6 +/- 1.4 g/day, respectively. The dose of warfarin
      in group A therefore decreased significantly different more than in group B. In
      conclusion, the normal prothrombin levels of patients atrial fibrillation
      increased more significantly than patients having sick sinus syndrome due to Af
      implanted with a cardiac pacemaker.

PMID- 12233105
TI  - [Arch translocation method for an arch aneurysm with open stent grafting using a
      nephrostomy catheter].
AB  - An 81-year-old female found to have an aneurysm in the distal aortic arch was
      successfully treated with arch translocation method. Under selective cerebral
      perfusion, a stent graft bound to a nephrostomy balloon catheter with a
      chainstitch was inserted from the ascending aorta into the descending aorta and
      its proximal end was sutured together with the distal aortic stump. Then a 4
      branched Dacron graft replaced the ascending aorta reconstructing cephalobracheal
      branches individually. Each proximal end of cephalobracheal branches was ligated.
      The patient had no neurological deficit except for recurrence nerve palsy that
      had already existed before the operation. Postoperative angiography revealed
      complete thrombocclusion of the aneurysm.

PMID- 12233107
TI  - [Cardiac surgery for chronic dialysis patients].
AB  - Chronic dialysis patients who received open heart surgery were examined, and main
      concern was perioperative management. There were 12 chronic dialysis patients and
      open heart surgeries were performed between October 1990 and June 2000. The
      patients were comprised of 7 men and 5 women with the average age being 64 with
      plus or minus 7.9. The operative procedure of 6 coronary artery bypass grafting
      (CABG) [on-pump], 1 CABG + mitral valve replacement (MVR), 3 aortic valve
      replacement (AVR), 1 mitral valvuloplasty (MVP) and 1 ascending aorta replacement
      were performed. All patients were discharged from the hospital with good
      conditions 27.1 days after operation. There were no hospital deaths. One
      postoperative complication of mediastinitis of the sternum has been found. A
      conventional dialysis was performed the day before the operation and an intra
      operative hemodialysis (HD) was performed, placing a dialyzer into a
      cardiopulmonary system during the operation. For the perioperative management, HD
      was started the day or 2 days after the operation with no immediate postoperative
      hemocatharsis and returned to the normal HD 7 days after the operation. The
      result of the perioperative management has been good.

PMID- 12233106
TI  - [Dor operation combined with redo coronary artery bypass grafting; report of two
      successful cases].
AB  - Case 1. A 69-year-old male, who had undergone coronary artery bypass grafting
      with saphenous vein graft for acute myocardial infarction 16 years previously,
      was admitted into our hospital for heart failure and recurrent angina. Coronary
      angiography showed occlusion of the graft and 75% stenosis in the proximal
      circumflex artery. Left ventriculography showed end-diastolic volume of 216 ml
      and ejection fraction of 24%. Dor operation combined with redo coronary artery
      bypass grafting was performed. Postoperatively, the ejection fraction improved to
      53% and the cardiac index improved from 1.8 to 2.2 l/min/m2. Case 2. A 67-year
      old male, who had undergone double coronary artery bypass grafting using
      saphenous vein grafts for acute myocardial infarction 8 years previously, was
      admitted into our hospital for heart failure and recurrent angina. Coronary
      angiography showed occlusion of the 2 grafts and 99% stenosis of the proximal
      left anterior descending artery. Although the left ventricle was slightly
      dilated, echocardiography demonstrated a thrombus in the left ventricle. Dor
      operation was performed concomitantly with removing of the thrombus and redo
      coronary artery bypass grafting. Postoperatively, the ejection fraction improved
      to 68% and the cardiac index improved from 1.6 to 2.3 l/min/m2. When the patients
      underwent coronary artery bypass surgery with saphenous vein grafts for acute
      myocardial infarction, they could be susceptible to left ventricular asynergy and
      graft failure on the long run. Therefore, the patients who need redo coronary
      revascularization may be potential candidates for Dor operation, and they require
      close examination regarding the myocardial viability, volume and shape of the
      left ventricle.

PMID- 12233109
TI  - [A difficult case of antiphospholipid syndrome with repeated restenosis of
      coronary artery and grafts].
AB  - A 65-year-old man complained of exertional angina. Coronary angiography revealed
      99% stenosis in the left anterior descending artery (LAD). He underwent
      percutaneous transluminal coronary angioplasty (PTCA) and stenting. Repeat
      angiography demonstrated restenosis of the previous PTCA and stenting site. He
      underwent coronary artery bypass grafting (CABG) with placement of the left
      internal thoracic artery (LITA) to LAD. Chest discomfort and V1-V3 ST elevation
      appeared on the first post operative day. Coronary angiography revealed occlusion
      of the LITA graft. He underwent re-operation. Because the radial artery was
      severely sclerotic, the great saphenous vein was used for the graft. Two weeks
      later, he began to show edema in the left lower extremity. Echoangiogram showed
      occlusion of the left deep vein with thrombus. He tested positive for
      anticardiolipin IgG and IgM antibodies. Eighteen months after re-operation, he
      had recurrent chest discomfort on exertion. Coronary angiography revealed 90%
      stenosis of the anastomosis (SVG-LAD). A second re-operation was performed. We
      used the right internal thoracic artery (RITA) for the graft. The postoperative
      angiography showed patent graft. The patient has been doing well without any
      complications.

PMID- 12233108
TI  - [Initial use of the newly developed voice-controlled robot system for a solitary
      pulmonary arterio-venous malformation].
AB  - We herein report an initial experience of thoracoscopic surgery for a solitary
      arterior-venous malformation (PAVM) with the AESOP 3000 HR voice-controlled robot
      to hold a thoracoscope. A 52-year-old woman was hospitalized due to a transient
      loss of consciousness. A brain magnetic resonance image and electroencephalogram
      (EEG) were normal. A chest computed tomogram indicated a suspicion of PAVM. The
      definite diagnosis of the PAVM was made by the 3-dimensional computed tomogram
      and pulmonary angiography. Thoracoscopic operation with the voice-controlled
      robot (AESOP 3000 HR) was conducted. The operating staffs were able to assemble
      the AESOP 3000 HR robotic system safely and quickly without difficulty. The robot
      functioned without problems throughout the procedure. No complications or events
      related or unrelated to the maneuvers of the robot during the operation were
      noted. The procedure of the pulmonary resection with the voice-controlled robot
      was successfully preformed by a single surgeon. The operating time was 110
      minutes, and the volume of the intraoperative bleeding was 10 g. The
      postoperative course was uneventful. The use of the AESOP 3000 HR robot may be
      more convenient and friendly in thoracoscopic procedure.

PMID- 12233110
TI  - [Surgical repair of left ventricular free wall rupture using layered fibrin glue
      sheet and fibrin glue; report of a case].
AB  - A 57-year-old man with acute myocardial infarction (#13:90%, #6-#8:75%) was
      admitted to our hospital after the administration of tissue plasminogen
      activator. Three hours' after emergent percutaneous transluminal coronary
      angioplasty, he developed left ventricular free wall rupture in the left
      circumflex artery area. After bleeding was completely controlled by aortic cross
      clamping, a three-layered of fibrin glue sheet (TachoComb) with fibrin glue was
      extensively applied to the ruptured site including the infarcted area. He was
      discharged on the 25th postoperative day and underwent coronary artery bypass
      grafting to the left anterior descending artery three weeks later. This
      experience suggests that the layered TachoComb and fibrin glue are effective for
      left ventricular free wall rupture.

PMID- 12233111
TI  - [Redo coronary artery bypass grafting using the patent left internal thoracic
      artery graft as an in flow with composite internal thoracic artery Y grafting;
      report of a case].
AB  - In redo coronary artery bypass grafting (CABG), graft selection and
      revascularization methods are major problems. We experienced a redo-CABG with
      occluded previous vein grafts. These grafts were to the circumflex artery and
      right coronary artery. We conducted operation using cardiopulmonary bypass. We at
      this operation, chose right internal thoracic artery (RITA) as a conduit and
      anastomosed it to the side of functioning left internal thoracic artery (LITA)
      graft, and then diogonal branch, posterolateral branch, and atrioventricular
      branch were revascularized with the RITA. Post operative course was uneventful.
      Internal thoracic artery (ITA) is superior to vein graft and other arterial graft
      as to long term patency. We believe composite Y graft with the use of bilateral
      ITA can be one of the revascularization strategy in redo CABG.

PMID- 12233112
TI  - [Aortobronchial fistula after replacement of descending thoracic aorta with
      ringed graft; report of a case].
AB  - A 79-year-old male patient complicated with aortobronchial fistula after
      replacement of descending thoracic aorta with ringed graft. He underwent
      replacement of the aortic arch using a four branched vascular graft and open
      stent grafting to replace the descending thoracic aorta after removing the ringed
      graft through median sternotomy. This procedure is useful for patients as the
      left thoracotomy is risky and the distal anastomotic site of the descending
      thoracic aorta is too far to anastomose.

PMID- 12233113
TI  - [Thymoma with idiopathic thrombocytopenic purpura preceded by mediastinal
      hemorrhage; report of a case].
AB  - A 62-year-old female with chest and right shoulder pain admitted to a hospital.
      The chest computed tomography (CT) scan showed a large anterior mediastinum mass
      with pleural effusion. Thymoma was suspected by percutaneous aspiration biopsy of
      it. She was referred to our hospital for operation with decreased serum platelet
      count (7.0 x 10(4)/microliter) and high platelet associated IgG (PA IgG) level
      (119.5 ng/10(7) cells). Result of bone marrow examination was normal,
      splenomegaly was not seen and no other autoimmune disease was not detected, so
      she was thought to have ITP. After giving her intravenous high-dose gamma
      globulin and her platelet count increased to normal, operation was done. Extended
      thymectomy was performed and postoperative course was uneventful. Pathological
      finding showed the mass mediastinum hematoma in thymus and there found a small
      thymoma. The hemorrhage was thought to occur from the thymoma. After the
      operation, her platelet count has not been changed to normal but remained lower
      level. Though myasthenia gravis, one of the autoimmune disease, improve after
      total thymectomy, it is thought that idiopathic thrombocytopenic purpura (ITP)
      could not improve after thymectomy.

PMID- 12233114
TI  - [Chylothorax after video-assisted thoracic surgery].
AB  - A 27-year-old male was admitted to our hospital with an abnormal shadow on chest
      X-ray. Chest computed tomography (CT) showed a localized mediastinal tumor.
      Thoracoscopic resection of the tumor was performed and the pathological diagnosis
      was bronchogenic cyst. Chylothorax occurred on postoperative day 1. Low fat diet
      therapy was performed. The discharge of chyliform pleural effusion was stopped on
      postoperative day 10. Thoracic drainage tube was removed and the patient
      discharged from hospital on postoperative day 19. He has been well for 10 months
      since operation, with no recurrence of the tumor or chylothorax.

PMID- 12233116
TI  - From e-strategy to implementation, the Web journey of Oakwood Healthcare.

PMID- 12233115
TI  - [Resection for pulmonary metastasis of gastrointestinal stromal tumor of the
      stomach at 10 years after gastrectomy; report of a case].
AB  - A 70-years-old male, who had received gastrectomy for leiomyosarcoma of the
      stomach 10 years ago, was found to have a left lung tumor on chest X-ray and
      computed tomography (CT). The tumor was diagnosed to be a pulmonary metastasis of
      gastric leiomyosarcoma. On admission, another tumor was detected at left
      occipital region by brain CT and was thought to be meningioma. Left lower
      lobectomy and brain tumor resection were performed serially. The histologic and
      immunohistochemical findings showed that both tumors were metastases of
      gastrointestinal stromal tumor (GIST) of the stomach after long disease-free
      interval. Compared with the primary tumor, cellular density, mitotic figures,
      bizarre nuclei, and necrotic foci were prominent in the metastatic tumors. This
      case suggest that GIST may recurrent as pulmonary metastasis after long disease
      free interval and should be follow up longer after resection. Patient prognosis
      with pulmonary metastases is considered to be reflected more exactly in
      biological malignant potential of metastatic tumor rather than that of primary
      tumor.

PMID- 12233117
TI  - Cleveland Clinic's new Web service helps patients research cancer treatment
      options.

PMID- 12233118
TI  - Harris four-country survey finds most health surfers positive about online
      healthcare information.

PMID- 12233119
TI  - Mercury reduction and elimination in healthcare facilities: an update.

PMID- 12233120
TI  - Healthcare's supply chain reaction.

PMID- 12233121
TI  - The digital hospital: looking before you leap.

PMID- 12233122
TI  - Our future leadership.

PMID- 12233123
TI  - Managing your vendor relationships.

PMID- 12233124
TI  - Promoting CAM services.

PMID- 12233125
TI  - The power of feedback.

PMID- 12233126
TI  - A fresh approach to funding.

PMID- 12233127
TI  - A Medicare reform package emerges.

PMID- 12233128
TI  - What makes a good boss?

PMID- 12233129
TI  - Redesign with customers in mind.

PMID- 12233130
TI  - Working with chief medical officers.

PMID- 12233131
TI  - Are you too wired?

PMID- 12233132
TI  - Maximizing the Internet to market to consumers.

PMID- 12233133
TI  - JCAHO: nursing shortage puts patients at risk, demands immediate attention.

PMID- 12233134
TI  - Poor communication is common cause of errors.

PMID- 12233136
TI  - Removing patient irritants improves care.

PMID- 12233135
TI  - QI project improves best practice use tenfold.

PMID- 12233137
TI  - Want to innovate? Look outside of health care.

PMID- 12233138
TI  - Develop a patient safety management system.

PMID- 12233139
TI  - Stunning HRT research points providers in new directions.

PMID- 12233140
TI  - Heart failure program proves that DM works--even under fee-for-service.
AB  - DM has a place in fee-for-service medicine. With ever-increasing pressures on the
      bottom line, a growing number of health care organizations are considering what
      DM can do to help them better meet their budgets as well as patient needs. In
      fact, even fee-for-service settings are experimenting with DM programs--in some
      cases, with solid success. See how a large integrated system in Minnesota was
      able to boost care of heart failure patients while turning a money-losing
      diagnosis into a profitable one.

PMID- 12233141
TI  - Sophisticated decision-support tools stay one step ahead of CVD.
AB  - Decision-support tools help providers put the focus on prevention. Cardiovascular
      disease is the nation's number one killer, and complications from this disease
      cost the health care system billions each year to treat. However, CVD can often
      be prevented if persons at risk are identified early so that interventions can
      begin. To assist providers in this process, a Longwood, FL-based company has
      unveiled two new tools designed to simplify risk identification and streamline
      patient tracking procedures so that providers can keep close tabs on care quality
      and patient progress.

PMID- 12233142
TI  - Resource kit designed to guide mental health providers toward an evidence-based
      approach.
AB  - Resource kits aim to elevate the prescribing patterns of mental health providers.
      Recognizing that there is little evidence to support many of the drug therapy
      choices made by mental health providers caring for individuals with severe mental
      illnesses, a nationwide effort is underway to help these providers base their
      decisions on solid evidence. Central to this effort is a new resource kit that
      will be distributed free of charge via the Internet. Get the details on how this
      kit is being developed and what it will offer.

PMID- 12233143
TI  - Retirement plan participation and features and standard of living of Americans 55
      or older.
AB  - This Issue Brief is the third in a series of Employee Benefit Research Institute
      (EBRI) publications based on data collected in 1998 and released in 2002 as the
      Retirement and Pension Plan Coverage Topical Module of the 1996 Survey of Income
      and Program Participation (SIPP). This report completes the series by examining
      the survey's more detailed questions concerning workers' employment-based
      retirement plans. Specifically, it examines the percentage of workers who are
      participating in a plan, and also workers' reasons for not participating in a
      plan when working in a job where a plan is sponsored; the features of, or
      decisions made concerning salary reduction plans; historical participation in
      employment-based retirement plans; and a comparison of the standard of living of
      individuals age 55 or older with their living standard in their early 50s. As of
      June 1998, 64.3 percent of wage and salary workers age 16 or older worked for an
      employer or union that sponsored any type of retirement plan (defined
      contribution or defined benefit) for any of its employees or members (the
      "sponsorship rate"). Almost 47 percent of these wage and salary workers
      participated in a plan (the "participation rate"), with 43.2 percent being
      entitled to a benefit or eligible to receive a lump-sum distribution from a plan
      if their job terminated at the time of survey (the "vested rate"). The
      predominant reason for choosing not to participate in a retirement plan was that
      doing so was unaffordable. The eligible participation rate for salary reduction
      plans was 81.4 percent. Fifty-six percent of all workers have participated in
      some type of retirement plan sometime during their work life through 1998. For
      those ages 51-60, almost 72 percent have ever participated in a plan. The median
      account balance in salary reduction plans in 1998 was $14,000. In 1998, 12.9
      percent of salary reduction plan participants eligible to take a loan had done
      so, and the average outstanding loan balance was $5,196. Nearly 80 percent of
      those age 55 or older reported that their standard of living is about the same or
      better now than it was when they were in their early 50s. The incidence of both
      pension income and health insurance from a former employer had a significant
      impact on retirees' ability to maintain their standard of living. In addition,
      those who spent their entire most recent lump-sum distribution were more likely
      to have a much worse standard of living in retirement than those who rolled over
      their entire most recent distribution.

PMID- 12233144
TI  - JCAHO approves National Patient Safety Goals for 2003.

PMID- 12233146
TI  - Revised behavior management and treatment standards approved for behavioral
      health care.

PMID- 12233145
TI  - New accreditation participation requirements approved.

PMID- 12233147
TI  - Sentinel event alert recommendation pool.

PMID- 12233148
TI  - New JCAHO accreditation options available for long-term care organizations.

PMID- 12233150
TI  - Rehabilitation therapy standards integrated for home care.

PMID- 12233149
TI  - Revised intent approved for assisted living on residents' lifestyle choices.

PMID- 12233151
TI  - Revisions approved for emergency management standards in home care.

PMID- 12233152
TI  - [Children with fever peaks and bone and joint pain: systemic juvenile idiopathic
      arthritis or acute lymphoblastic leukemia after all?].
AB  - In two 3-year-old infants, a girl and a boy, systemic juvenile idiopathic
      arthritis was suspected because of daily fever peaks, signs of polyarthritis and
      general malaise. Drug treatment was unsuccessful, and after extensive laboratory
      investigation acute lymphoblastic leukaemia (ALL) was diagnosed and treated
      adequately. ALL is the most common malignancy in childhood. About one-third of
      the patients present with joint or bone pain and fever. In this group of
      children, it can be difficult to identify ALL because it may mimic the clinical
      picture of systemic juvenile idiopathic arthritis and because of the possibility
      of a normal blood count at presentation. ALL should always be considered in the
      differential diagnosis in children with musculoskeletal pain and fever, even in
      the face of a normal blood count. In any case, a bone-marrow examination should
      be done before steroid treatment is given.

PMID- 12233153
TI  - [Eye problems due to contact lenses; an advisory report from the Health Council
      of the Netherlands].
AB  - In a recent report, the Committee on Health Risks of Contact Lenses from the
      Health Council of the Netherlands evaluated the health risks of contact lens wear
      in the Netherlands. Contact lens-related eye disease appears to be common, with
      an incidence of approximately 80,000 persons per year, who suffer from self
      limiting or mild conditions. Such conditions are multifactorial, caused for
      example by chronic hypoxia, tear-film dysfunction or inadequate fit of the lens.
      They can range from ocular irritation to giant papillary conjunctivitis, a common
      cause of permanent lens intolerance. A very serious complication of contact lens
      wear is infectious keratitis, caused by bacteria or fungi. This is most common in
      users of permanent-wear soft lenses (20 per 10,000 persons per year) and can lead
      to a severe loss of vision. Therefore, the Committee has recommended that
      permanent-wear lenses should not be used. Moreover, lens fitting and follow-up of
      contact lens wearers should be a prerequisite for optometrists and
      ophthalmologists. However, the Dutch government has not taken action with respect
      to this last recommendation.

PMID- 12233154
TI  - [Research code at the Academic Medical Center in Amsterdam: useful].
AB  - At the Academic Medical Centre (AMC) of the University of Amsterdam, the
      Netherlands, it was decided to set up a research code committee. The first thing
      that was done was to define what were considered the most relevant types of
      scientific misconduct: falsification, plagiarism and invasion of privacy. The
      committee decided that prevention is better than cure and therefore developed a
      guideline for desirable behaviour, i.e. how to act scientifically with care and
      integrity, instead of a guideline on what not to do. The committee also proposed
      an ombudsman whose services are available to all participants in research in the
      AMC, and to whom misconduct can be reported. The research code is a loose-leaf
      system, since new issues will come to the fore and included issues will need to
      be changed. This committee has created a code that provides a firm basis for
      scientific integrity within the AMC.

PMID- 12233155
TI  - [Reporting of scientific misconduct in health care research].
AB  - The incidence of scientific dishonesty in the Netherlands is not known, yet
      experiences at both the NWO (the Netherlands Organization for Scientific
      Research) and Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine)
      indicate that there must be several cases per year. For scientific fraud to be
      prevented students and researchers should receive thorough teaching, and in
      research laboratories an emphasis should be placed upon integrity. The Academic
      Medical Centre in Amsterdam has published a research protocol which is perfect
      for internal use. The Royal Netherlands Academy of Arts and Sciences publishes
      brochures on good research practice for researchers, teachers and students. The
      NWO and the Vereniging van Universiteiten (Dutch Association of Universities)
      have set up a committee for scientific integrity to function as a fallback
      mechanism and to assess the institutional procedures or to repeat the inquiries.
      As healthcare research institutions other than universities are involved since
      authorities are not always objective, an independent committee has been
      established to assess complaints about scientific dishonesty, the Scientific
      Integrity Health Research. Like the Committee on Publication Ethics it will
      publish its cases anonymously on an annual basis. Its judgments will be
      communicated to the people involved and the proper authorities.

PMID- 12233156
TI  - [The disc prosthesis: myths and facts].
AB  - The results of surgical treatment of degenerative low-back conditions by means of
      a fusion (spondylodesis) are in general less predictable than operative
      treatments for arthrosis of the (large) peripheral joints. Recently, new
      techniques of disc replacement have been developed as an alternative to
      traditional fusion operations. The most important theoretical advantage is the
      prevention of adjacent segment degeneration in the longer term. Because the disc
      prosthesis replaces the presumably painful intervertebral disc--just as an
      intercorporal fusion--the short-term results are expected to be comparable to
      ventral fusion. The results with a short follow-up period described in the
      literature are comparable to those published for spondylodesis. However, disc
      prosthesis requires a more extensive approach and therefore more serious
      complications are to be expected. In the longer term, prosthesis-related
      complications can be expected because these prostheses are used in young and
      active patients. Despite 15 years of small-scale experience in some European
      countries, there is a lack of reliable information about the middle and long-term
      performance of these prostheses in the peer-reviewed literature. Therefore, these
      implantations should be regarded as experimental procedures and should be
      confined to clinical trials in centres with sufficient experience in the
      operative treatment of degenerative low-back conditions as well as the necessary
      infrastructure to follow up these usually young patients in a scientifically
      responsible manner over a period of decades. These centres should also have the
      expertise necessary to adequately deal with the possible complications.

PMID- 12233157
TI  - [Medical maintenance treatment of chronic obstructive pulmonary disease (COPD)].
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic disorder of the lungs
      and airways that imposes a huge socioeconomic burden on both the patients and
      society. COPD is the only major chronic disease for which both the incidence and
      mortality are still rising worldwide. From the literature evidence-based insights
      can be obtained about maintenance medication for reducing symptoms and disease
      progression. Both anticholinergics and beta 2-sympathicomimetics have been proven
      to be effective bronchodilators for COPD, even though many patients fail to
      respond. This is confounded by the fact that a symptomatic response is not always
      reflected by an objective improvement in lung function. These substances do not
      have a favourable effect on the progressive deterioration of lung function.
      Theophyllines have limited effectiveness and the benefit-to-risk ratio is
      unfavourable. It has now been demonstrated that inhaled corticosteroids have no
      effect on the loss of lung function, and their prescription rates in patients
      with COPD should therefore be reduced. A reduction in exacerbation frequency
      seems to exist in some studies, yet this has not yet been conclusively
      demonstrated. Acetylcysteine has been proven to reduce exacerbation frequency.
      There is no place for maintenance therapy with antibiotics.

PMID- 12233158
TI  - [Citing electronic sources in scientific articles].
AB  - In 1995 a reference to an electronic source of information first appeared in this
      journal. Such sources are neither permanently available nor unchangeable. Both
      qualities are of central importance to the progress of scientific knowledge.
      Readers must have the opportunity to check the information referred to in
      scientific publications. It is scientifically useless to refer to a source that
      readers may not be able to find or where they find something else than the
      authors did when they wrote their article. However, electronic media, volatile as
      they may be, can be a very useful means of alerting readers to medical scientific
      developments. Therefore the editors of this journal have chosen to accept
      references to electronic information by way of a 'written communication' in
      parentheses in the text, until electronic scientific information is stored in an
      unalterable and generally accessible permanent form. The list of references at
      the end of scientific articles will be reserved to generally available paper and
      CD-ROM sources.

PMID- 12233159
TI  - [Diagnostic image (103). A pregnant woman with itching].
AB  - A 30-year-old woman in her first, twin, pregnancy presented with progressive
      erythematous edematous papulae and pruritus at 31 weeks amenorrhoea. She was
      diagnosed with polymorphic eruption of pregnancy. The symptoms disappeared after
      elective cesarean section at 36 weeks.

PMID- 12233160
TI  - [The adverse effects of smoking on healing of open tibial fractures].
AB  - OBJECTIVE: Survey of the influence of smoking on the healing of open tibial
      fractures. DESIGN: Retrospective. METHOD: During the period 1 January 1994 to 31
      December 2000, 168 patients were treated at the Department of Surgery (University
      Medical Center Utrecht, the Netherlands) due to an open tibial fracture; 118
      patients with 125 fractures were included in the study. On the basis of their
      smoking behaviour, patients were classified as 'non-smokers' or 'smokers'. For
      all of the patients it was ascertained whether or not complications had occurred
      during treatment. Whether the fracture had consolidated was determined on the
      basis of clinical and radiological criteria. RESULTS: Seventy-two (61%) patients
      were non-smokers and 46 were smokers. The non-smokers had 77 open tibial
      fractures and the smokers 48. Initial therapy was identical and wound infections
      occurred with similar incidences in both groups. However, there was a
      statistically significant difference in the incidence of osteitis between both
      groups: 7 (9%) times in the non-smokers and 13 (27%) times in smokers (p = 0.04).
      The mean time to consolidation was 26 weeks for non-smokers and 33 weeks for
      smokers (p = 0.04). Smokers remained longer in hospital and underwent more re
      operations. CONCLUSIONS: Smoking was negatively associated with the healing of
      open tibial fractures. In smoking patients, the time to consolidation was on
      average statistically significantly longer and they suffered more from osteitis.

PMID- 12233162
TI  - [Haemophilus influenzae type a as the causative agent of meningitis in an
      infant].
AB  - A 6-month-old girl had been ill with a cold for several days and was increasingly
      drowsy. She had been fully vaccinated against Haemophilus influenzae type b and
      had meningitis due to H. influenzae type a. She made a complete recovery after
      treatment with ceftriaxone and amoxicillin. In the Netherlands, vaccination with
      the conjugated H. influenzae type b vaccine was started in 1993 and since then
      invasive infections caused by H. influenzae type b have almost disappeared.
      Vaccination may suppress carriership of H. influenzae type b. However,
      vaccination does not elicit cross-protective antibodies against other serotypes
      of H. influenzae. H. influenzae non-type b may profit from the vaccination state,
      resulting in a higher carrier rate and an increased incidence of invasive
      infections. In the Netherlands, H. influenzae type a as the causative agent of an
      invasive infection has been recorded for the first time since registration
      started in 1975 and since then five such cases have been reported. In the
      literature, 45 cases of infection with H. influenzae type a have been described
      up until now.

PMID- 12233163
TI  - [Acute right heart failure due to aortic aneurysm: 2 patients with an aortocaval
      shunt].
AB  - Two patients, a 72-year-old man and a 34-year-old woman, presented with severe
      pain in the lower back and abdomen, respectively, accompanied by acute dyspnoea.
      One patient presented additionally with a palpable pulsatile abdominal mass and a
      continuous harsh bruit. He subsequently developed massive haemoptysis and went
      into deep shock. The second patient presented with peripheral cyanosis and a loud
      systolic heart murmur. She developed increasing respiratory distress and was
      maximally supported in the intensive care unit. Further investigation revealed
      acute left-to-right shunting based on rupture of an aortic aneurysm into the
      venous system in both patients; in the first this was into the V. cava inferior
      and in the second this was into the right atrium. In both patients, high-output
      heart failure was present. Acute right heart failure due to a fistula between the
      aorta and the venous system is a life-threatening and rapidly worsening
      haemodynamic disturbance. The diagnosis is not difficult but the condition is
      rare. In some cases, the patient's survival can be achieved by prompt diagnosis
      followed by operative closure of the fistula.

PMID- 12233164
TI  - [Hallucinations caused by paroxetine taken together with a levodopa-carbidopa
      preparation].

PMID- 12233165
TI  - [Pulmonary problems associated with lymphoplasmacytic lymphoma (Waldenstrom's
      macroglobulinemia)].

PMID- 12233166
TI  - [Signs of miliary tuberculosis: which diagnostic tests and when to treat?].

PMID- 12233167
TI  - No cause for alarm in IBS.

PMID- 12233168
TI  - Managing reflux oesophagitis.

PMID- 12233169
TI  - The GP's role in gallstone disease.

PMID- 12233170
TI  - Diagnosis and treatment of oesophageal cancer.

PMID- 12233171
TI  - Current thinking in coeliac disease.

PMID- 12233172
TI  - Rectal bleeding: history is key.

PMID- 12233173
TI  - Subarachnoid haemorrhage.
AB  - Aneurysmal SAH is a devastating condition arising suddenly and usually without
      warning. The best outcomes may be facilitated by prompt recognition/suspicion and
      immediate referral to the neurosurgical unit. Many contentious issues surround
      this subject and the ISAT trial should resolve many of these. Modern developments
      alongside evidence-based practice should hopefully optimise results.

PMID- 12233175
TI  - Mechanisms influencing the evolution of resistance to Qo inhibitor fungicides.
AB  - Fungicides inhibiting the mitochondrial respiration of plant pathogens by binding
      to the cytochrome bc1 enzyme complex (complex III) at the Qo site (Qo inhibitors,
      QoIs) were first introduced to the market in 1996. After a short time period,
      isolates resistant to QoIs were detected in field populations of a range of
      important plant pathogens including Blumeria graminis Speer f sp tritici,
      Sphaerotheca fuliginea (Schlecht ex Fr) Poll, Plasmopara viticola (Berk & MA
      Curtis ex de Bary) Berl & de Toni, Pseudoperonospora cubensis (Berk & MA Curtis)
      Rost, Mycosphaerella fijiensis Morelet and Venturia inaequalis (Cooke) Wint. In
      most cases, resistance was conferred by a point mutation in the mitochondrial
      cytochrome b (cyt b) gene leading to an amino-acid change from glycine to alanine
      at position 143 (G143A), although additional mutations and mechanisms have been
      claimed in a number of organisms. Transformation of sensitive protoplasts of M
      fijiensis with a DNA fragment of a resistant M fijiensis isolate containing the
      mutation yielded fully resistant transformants, demonstrating that the G143A
      substitution may be the most powerful transversion in the cyt b gene conferring
      resistance. The G143A substitution is claimed not to affect the activity of the
      enzyme, suggesting that resistant individuals may not suffer from a significant
      fitness penalty, as was demonstrated in B graminis f sp tritici. It is not known
      whether this observation applies also for other pathogen species expressing the
      G143A substitution. Since fungal cells contain a large number of mitochondria,
      early mitotic events in the evolution of resistance to QoIs have to be
      considered, such as mutation frequency (claimed to be higher in mitochondrial
      than nuclear DNA), intracellular proliferation of mitochondria in the
      heteroplasmatic cell stage, and cell to cell donation of mutated mitochondria.
      Since the cyt b gene is located in the mitochondrial genome, inheritance of
      resistance in filamentous fungi is expected to be non-Mendelian and, therefore,
      in most species uniparental. In the isogamous fungus B graminis f sp tritici,
      crosses of sensitive and resistant parents yielded cleistothecia containing
      either sensitive or resistant ascospores and the segregation pattern for
      resistance in the F1 progeny population was 1:1. In the anisogamous fungus V
      inaequalis, donation of resistance was maternal and the segregation ratio 1:0. In
      random mating populations, the sex ratio (mating type distribution) is generally
      assumed to be 1:1. Therefore, the overall proportion of sensitive and resistant
      individuals in unselected populations is expected to be 1:1. Evolution of
      resistance to QoIs will depend mainly on early mitotic events; the selection
      process for resistant mutants in populations exposed to QoI treatments may follow
      mechanisms similar to those described for resistance controlled by single nuclear
      genes in other fungicide classes. It will remain important to understand how the
      mitochondrial nature of QoI resistance and factors such as mutation,
      recombination, selection and migration might influence the evolution of QoI
      resistance in different plant pathogens.

PMID- 12233176
TI  - Toxicological and mechanistic studies on neonicotinoid cross resistance in Q-type
      Bemisia tabaci (Hemiptera: Aleyrodidae).
AB  - The tobacco whitefly, Bemisia tabaci Gennadius (Homoptera: Aleyrodidae) is a
      serious pest in numerous cropping systems and has developed a high degree of
      resistance against several chemical classes of insecticides. One of the latest
      group of insecticides introduced to the market were the neonicotinoids
      (chloronicotinyls), acting agonistically on insect nicotinic acetylcholine
      receptors. Resistance to neonicotinoid insecticides has recently been shown to
      occur, especially in Q-type B tabaci in some places in Almeria, Spain, whereas
      control of B-type B tabaci in many other intense cropping systems worldwide has
      remained on high levels. Our study revealed that neonicotinoid-resistant Q-type
      strains from Almeria were often more than 100-fold less susceptible to
      thiamethoxam, acetamiprid and imidacloprid when tested in discontinuous systemic
      laboratory bioassays. The resistance factors were generally 2- to 3-fold lower in
      leaf-dip bioassays. In addition to the Spanish strains, we obtained two other
      highly neonicotinoid-cross-resistant B tabaci greenhouse populations, one from
      Italy (December 1999) and one from Germany (June 2001). A molecular diagnostic
      analysis revealed that both strains also belong to the (Spanish) subtype Q of the
      B tabaci species complex. The resistance levels of Q-type whitefly strains
      derived from Almeria greenhouses in 1999 remained stable for at least two years,
      even when maintained in the laboratory without any selection pressure. The
      biochemical mechanisms conferring resistance to neonicotinoids have not yet been
      elucidated in detail, but synergist studies suggested a possible involvement of
      microsomal monooxygenases. Furthermore, we checked two Almerian strains of B
      tabaci isolated in 1998 and 1999 and demonstrated that neonicotinoid resistance
      is not due to an altered [3H]imidacloprid binding site of nicotinic acetylcholine
      receptors.

PMID- 12233177
TI  - Mechanisms of resistance to fungicides in field strains of Botrytis cinerea.
AB  - Field strains of Botrytis cinerea Pers ex Fr, the causal agent of grey mould
      diseases, were collected from French vineyards between 1993 and 2000. Several
      phenotypes have been characterized according to the inhibitory effects of
      fungicides towards germ-tube elongation and mycelial growth. Two types of
      benzimidazole-resistant strains (Ben R1 and Ben R2) could be detected; negative
      cross-resistance to phenylcarbamates (e.g. diethofencarb) was only found in Ben
      R1. Benzimidazole resistance was related to point mutations at codon 198 (Ben R1)
      or 200 (Ben R2) of the beta-tubulin gene. Most dicarboximide-resistant strains
      were also weakly resistant to aromatic hydrocarbon fungicides (e.g. dicloran) but
      remained sensitive to phenylpyrroles (e.g. fludioxonil). These resistant field
      strains (Imi R1) contained a single base pair mutation at position 365 in a two
      component histidine kinase gene, probably involved in the fungal osmoregulation.
      Three anilinopyrimidine-resistant phenotypes have been identified. In the most
      resistant one (Ani R1), resistance was restricted to anilinopyrimidines, but no
      differences were observed in the amino-acid sequences of cystathionine beta-lyase
      (the potential target site of these fungicides) from Ani R1 or wild-type strains.
      In the two other phenotypes (Ani R2 and Ani R3), resistance extended to various
      other groups of fungicide, including dicarboximides, phenylpyrroles and sterol
      biosynthesis inhibitors. This multi-drug resistance was probably determined by
      over-production of ATP-binding cassette transporters. The hydroxyanilide
      fenhexamid is a novel botryticide whose primary target site is the 3-keto
      reductase involved in sterol C-4 demethylations. Apart from the multi-drug
      resistant strain Ani R3, three other fenhexamid-resistant phenotypes have been
      recognized. For two of them (Hyd R1 and Hyd R2) fenhexamid-resistance seemed to
      result from P450-mediated detoxification. Reduced sensitivity of the target site
      could be the putative resistance mechanism operating in the third resistant
      phenotype (Hyd R3). Increased sensitivity to inhibitors of sterol 14 alpha
      demethylase recorded in Hyd R1 strains was related to two amino-acid changes at
      positions 15 and 105 of this enzyme.

PMID- 12233178
TI  - Amplified esterase genes and their relationship with other insecticide resistance
      mechanisms in English field populations of the aphid, Myzus persicae (Sulzer).
AB  - Myzus persicae samples were collected from populations present on a range of
      field crops between 1997 and 2000. A combination of biochemical, DNA-based
      diagnostics and bioassays was used to assess the presence of three insecticide
      resistance mechanisms: elevated carboxylesterase (E4 or FE4), insensitive
      acetylcholinesterase and insensitive sodium channels (knockdown resistance, kdr).
      For the carboxylesterases, both the levels of enzyme and the type of gene present
      (E4 or FE4) were determined. The results showed that during the time period
      studied there was a dramatic reduction in the proportion of aphids with very high
      levels of E4 and an increase in those with lower levels of FE4. There was also a
      slightly different E4 gene present in a limited number of samples. The change in
      esterase genes was accompanied by a virtual loss of the insensitive AChE variant
      and a maintenance of aphids with kdr. The selection pressures and other factors
      leading to these changes in field populations of M persicae are discussed.

PMID- 12233179
TI  - Temporal and spatial dynamics of insecticide resistance in Myzus persicae
      (Hemiptera: Aphididae).
AB  - Advances in understanding insecticide resistance in the peach-potato aphid, Myzus
      persicae (Sulzer), at the genotypic, biochemical and molecular levels have led to
      rapid and precise methods for the detection of several resistance mechanisms
      (elevated carboxylesterase, modified acetylcholinesterase or MACE, and knockdown
      resistance or kdr) in individual insects, and for monitoring their frequencies
      over space and time. This paper summarises the results of two long-term surveys
      of resistance dynamics in M persicae in England, based on samples collected
      directly from field and glasshouse crops or from four 12.2-m suction traps. The
      study showed marked fluctuations in resistance frequencies that probably reflect
      the counteracting forces of selection imposed by insecticides for aphids
      possessing more copies of esterase resistance genes, and selection against these
      forms when insecticide use is relaxed. There is growing evidence that several
      different resistance mechanisms in M persicae have associated fitness costs. In
      the case of esterase and MACE, these costs are apparently strong enough to effect
      a decline in resistance frequency over winter, and a more prolonged decline over
      successive cropping seasons when aphid numbers are insufficient to trigger
      intensive chemical applications. Changes in the overall frequency of resistance
      genotypes may also be influenced by the predominance of year-round
      parthenogenesis in M persicae in the UK, leading to non-random associations
      between mechanisms and selection operating on clonal lineages rather than
      individual genotypes.

PMID- 12233180
TI  - A non-Mendelian inheritance of resistance to strobilurin fungicides in Ustilago
      maydis.
AB  - Mutants of Ustilago maydis (DC) Corda with high resistance to azoxystrobin (RF
      164 to 4714, based on EC50 values), an inhibitor of mitochondrial electron
      transport at the cytochrome bc1 complex, were isolated in a mutation frequency of
      2.3 x 10(-7) after nitrosoguanidine mutagenesis and selection on media containing
      1 microgram ml-1 azoxystrobin in addition to 0.5 mM salicylhydroxamate (SHAM), a
      specific inhibitor of cyanide-resistant (alternative) respiration. Oxygen uptake
      in whole cells was strongly inhibited in the wild-type strains by azoxystrobin
      (1.5 micrograms ml-1) in addition to SHAM (1 mM), but not in the mutant isolates.
      Genetic analysis with nine such mutant isolates resulted in progeny phenotypes
      which did not follow Mendelian segregation, but satisfied the criteria of non
      Mendelian (cytoplasmic) heredity. In crosses between three mutant isolates with
      the compatible wild-type strains, the sensitivity was inherited by progeny
      maternally from the wild-type parent strain (criterion of uniparental
      inheritance). In crosses between wild-type strains and remaining mutant isolates,
      a continuous distribution of sensitivity in the progeny was found (criterion of
      vegetative segregation). The third criterion of cytoplasmic resistance (criterion
      of intracellular selection) was fulfilled by experiments on the stability of
      resistance phenotypes. With two exceptions, a reduction of resistance was
      observed in the mutant strains when they were grown on inhibitor-free medium.
      Recovery of the high resistance level was observed after they were returned to
      the selection medium. Cross-resistance studies with other fungicides, which also
      inhibit electron transport through complex III of respiratory chain, showed that
      mutations for resistance to azoxystrobin were also responsible for reduced
      sensitivity to kresoxim-methyl (RF 18 to 1199) and to antimycin-A (RF 20 to 305),
      which act at the Qo and Qi sites of the cytochrome bc1 complex, respectively.
      Studies of the fitness of azoxystrobin-resistant isolates showed that these
      mutations appeared to be pleiotropic, having significant adverse effects on
      growth in liquid culture and pathogenicity on young corn plants.

PMID- 12233181
TI  - Cross-resistance to imidazolinone herbicides in chlorsulfuron-resistant Raphanus
      raphanistrum.
AB  - Raphanus raphanistrum L has evolved widespread resistance to sulfonylureas in the
      Western Australia (WA) wheat belt. With the introduction of imidazolinone
      tolerant (IT) wheat (Tritcum aestivum L) and IT canola (Brassica napus L) in the
      WA wheat belt, it is important to understand the status of cross-resistance in
      this weed to sulfonylurea and imidazolinone (Imi) herbicides. A study was
      conducted to examine cross-resistance between chlorsulfuron and Imi herbicides (a
      mixture of imazapic and imazapyr) in 46 R raphanistrum populations collected from
      across the WA wheat belt. Plants were treated with herbicides and assessed for
      phytotoxicity under glasshouse conditions. Of the 46 R raphanistrum populations,
      32 were resistant to chlorsulfuron and four were resistant to imazapic +
      imazapyr. Of the 70% chlorsulfuron-resistant populations, 13% showed cross
      resistance to imazapic + imazapyr. However, the cross-resistant populations
      treated with imazapic + imazapyr showed a lower resistance level than the
      chlorsulfuron-treated populations. These results suggest that weed populations
      with such cross-resistance will not be controlled effectively by Imi herbicides.
      Although the resistance levels of the cross-resistant populations to Imi
      herbicides were low, the cross-resistance levels of R raphanistrum should be
      determined before growing IT crops, particularly IT canola.

PMID- 12233182
TI  - Field and laboratory selection of Frankliniella occidentalis (Pergande) for
      resistance to insecticides.
AB  - Response of western flower thrips, Frankliniella occidentalis (Pergande), to
      selection for resistance to insecticides commonly used to control this pest in
      Murcia (south-east Spain) was studied under field and laboratory conditions. In
      the field, plots within sweet pepper crops in commercial and experimental
      greenhouses were treated under different selection strategies: insecticide
      rotation versus formetanate reiteration, formetanate reiteration versus
      acrinathrin reiteration, and formetanate reiteration versus methiocarb
      reiteration. Thrips populations were sampled monthly and bioassayed against
      methiocarb, methamidophos, acrinathrin, endosulfan, deltamethrin and formetanate.
      In the laboratory, F occidentalis strains were selected against each insecticide
      for several generations. To evaluate cross-resistance, each selected strain was
      bioassayed with the other insecticides. Frankliniella occidentalis populations
      showed a rapid development of acrinathrin resistance, reaching high levels in
      field and laboratory conditions. Formetanate and methiocarb resistance were also
      observed, although development was slower and at moderate levels. Cross
      resistances between acrinathrin/deltamethrin and acrinathrin/formetanate were
      detected under field and laboratory conditions. Formetanate/methiocarb cross
      resistance was suspected in laboratory selections, but not in field assays.
      Simultaneous moderate resistance levels to the three specific insecticides
      against thrips (formetanate, methiocarb and acrinathrin) were shown in laboratory
      selection strains, indicating a general mechanism of resistance, probably
      metabolic.

PMID- 12233183
TI  - Evaluation of metabolic detoxifying enzyme activities and insecticide resistance
      in Frankliniella occidentalis.
AB  - The western flower thrips Frankliniella occidentalis (Pergande) is a very
      significant pest of a number of different agricultural crops in the south-east of
      Spain. The importance of thrips as a pest is not due mainly to the direct damage
      inflicted on the plant, but to the loss in commercial value which occurs as a
      consequence of the development of dark spots caused by the tomato spotted wilt
      virus (TSWV) which they transmit. The economic threshold is therefore almost
      zero, which enhances the problems of resistance management. The present work is
      part of a global project that attempts to evaluate the status of insecticide
      resistance in field populations of thrips obtained from several agricultural
      crops. We have studied, in either individual or pooled insects, some enzyme
      systems classically related to detoxification of insecticides: esterase and
      glutathione-S-transferase (GST). The activity of these enzymes from laboratory
      populations selected with various classes of insecticides has also been measured
      using several appropriate substrates. An increase in GST mean activity was found
      in two field-collected strains. Differences in frequency distributions of
      esterase and GST activities were found for both field-collected strains and for a
      laboratory strain selected with acrinathrin. These activities were compared with
      those of a wild-type reference strain.

PMID- 12233185
TI  - What impact will EPPO's new resistance risk assessment guideline have on
      selection pressure in the European Union?
AB  - This paper examines practical and regulatory implications, including both costs
      and benefits, resulting from implementation of EPPO's new resistance risk
      analysis guideline. Crop-protection companies operating in Europe are preparing
      risk analyses and management strategies, and are monitoring for resistance.
      However, this is a complex and expensive process involving technical, commercial
      and regulatory functions. The actual cost of filling these data gaps is
      consequently greater than many would have anticipated. The agrochemical industry
      has a vested interest in managing resistance and is committed to maintaining the
      essential contribution of crop-protection products to sustainable agriculture.
      However, with increasing regulatory costs, it is important that regulatory
      authorities concentrate requirements for resistance risk analyses, management
      strategies and monitoring where these are most needed. Should these requirements
      be applied indiscriminately, crop-protection companies will have to consider
      whether or not it is economically justifiable to make these investments, or
      whether to remove less profitable uses from product labels. In such situations,
      minor crops stand to be disproportionately effected. One year after publication,
      it is too early to measure the guideline's impact on selection pressure. It is
      already clear that the guideline represents an unprecedented step forward in the
      regulation and harmonisation of resistance management. There are, however, valid
      arguments against regulation of resistance management. One of the most important
      criticisms that is levelled against the latter approach is that, with the best
      motivation and with appropriate use restrictions on labels, these actions alone
      do not solve the problem. It is critical that all stakeholders in the crop
      protection process are made aware of the importance of resistance management and
      of complying with prescribed strategies.

PMID- 12233184
TI  - EU regulatory aspects of resistance risk assessment.
AB  - The EPPO Standard PP 1/213(1) on resistance risk analysis is the basis for risk
      assessment within the authorisation process in Germany. Data for resistance risk
      analysis have to be provided by the applicant and risk-mitigation strategies
      prepared if necessary. The extent of data requirements and the intensity of the
      evaluation process depend mainly on the type of target organism, crop, mode of
      action of the active substance and the resistance history of the organism in
      combination with products of similar mode of action as the one being applied for.
      Because resistance risk is a very complicated issue during the authorisation of
      plant-protection products, intensive co-operation between applicants and
      regulators is essential prior to submission of the dossier, with due
      consideration of the amount of data necessary and, where required, the proposed
      resistance-management strategy.

PMID- 12233186
TI  - Phytophthora infestans: populations, pathogenicity and phenylamides.
AB  - Isolates of Phytophthora infestans (Mont) de Bary (the potato and tomato late
      blight pathogen) resistant to phenylamides appeared in Europe and North America
      in the late 1970s and early 1990s respectively. Concurrent, but coincidentally,
      with both these events there were radical structural shifts in the pathogen
      populations as immigrant genotypes from Mexico displaced the indigenous
      populations. Both A1 and A2 mating type isolates are now present in blighted
      crops, permitting alternative inoculum via germinating sexually produced oospores
      to influence dynamics of late blight populations. Studies of inheritance of
      ploidy, host-specific pathogenicity, mating type and resistance to antibiotics
      and phenylamide fungicides have provided insight into mechanisms of variation in
      this potent pathogen.

PMID- 12233187
TI  - Population changes in Phytophthora infestans in Taiwan associated with the
      appearance of resistance to metalaxyl.
AB  - In recent years, late blight, caused by Phytophthora infestans (Mont) De Bary,
      has increased in severity in many parts of the world, and this has been
      associated with migrations which have introduced new, arguably more aggressive,
      populations of the pathogen. In Taiwan, late blight has been endemic on outdoor
      tomato crops grown in the highlands since the early 1900s, but recent epidemics
      have been more damaging. To ascertain the present status of the Taiwanese
      population of P infestans, 139 isolates of the pathogen collected and maintained
      by the Asian Vegetable Research and Development Center (AVRDC) were characterized
      using mating type, metalaxyl sensitivity, allozyme genotype, mitochondrial
      haplotype and RFLP fingerprinting. Up to 1997, all isolates were found to belong
      to the old clonal lineage of P infestans (US-1 and variants), but in isolates
      from 1998 a new genotype appeared, and by 2000 this had apparently completely
      displaced the old population. This new genotype was an A1 mating type and has the
      dilocus allozyme genotype 100/100/111, 100/100 for the loci coding for glucose-6
      phosphate isomerase and peptidase, respectively. These characters, together with
      RG57 fingerprinting, indicated that these isolates belonged to the US-11 clonal
      lineage, a minority (11%) being a previously unreported variant of US-11. Whereas
      metalaxyl-resistant isolates were not detected in the old population, 96% of the
      new genotypes proved resistant, with the remainder being intermediate in
      sensitivity. It may be inferred from this sudden, marked change in the
      characteristics of the Taiwanese P infestans that a new population of the
      pathogen was introduced around 1997-98 and that this may well have already been
      metalaxyl-resistant when it arrived, although a role for in situ selection cannot
      be excluded.

PMID- 12233188
TI  - Natural variation in baseline data: when do we call a new sample 'resistant'?
AB  - Mortality of pear psylla to amitraz was studied by means of bioassays. Variation
      between samples, temporal variation within the season in one orchard and spatial
      variation between Swiss regions were considered. Variation between samples was
      large enough to produce different Probit functions and LC50 values. Temporal and
      spatial variations were too small to indicate resistance. Prediction intervals of
      the pooled functions using bootstrapping were calculated to determine if future
      samples come from a population with decreased sensitivity. Probabilistic criteria
      on the population level were proposed for resistance.

PMID- 12233189
TI  - Establishment of the baseline sensitivity and monitoring response of Papaver
      rhoeas populations to florasulam.
AB  - In accordance with the EPPO guideline for the efficacy evaluation of plant
      protection products, resistance risk analysis PP 1/213(1), a method was
      established to determine the baseline sensitivity of key weed species to
      florasulam, a new triazolopyrimidine sulfonanilide herbicide for post-emergence
      control of dicotyledonous weeds in cereals. The aim of the baseline monitoring
      project was to understand the natural variation in response to florasulam of
      diverse populations of Papaver rhoeas at the time of product launch. The method
      entailed seed collection from representative agricultural areas throughout
      Europe. The seed was subjected to glasshouse tests where dose-response studies
      were conducted and ED80 values generated. This enabled a sensitivity index to be
      calculated for each country, giving an indication of the variation in P rhoeas
      response to florasulam in the populations tested.

PMID- 12233190
TI  - Insecticide resistance in field populations of Frankliniella occidentalis
      (Pergande) in Murcia (south-east Spain).
AB  - Thirty-nine field populations of Frankliniella occidentalis (Pergande) were
      collected from different crops (sweet pepper, tomato, lettuce, artichoke, melon,
      cucumber, carnation, broad bean, peach and plum) in Murcia (south-east Spain).
      All populations were reared separately in the laboratory to obtain enough
      individuals for bioassays. Female thrips were bioassayed, using a standard
      topical application method, against methiocarb, methamidophos, acrinathrin,
      endosulfan, deltamethrin and formetanate. Methiocarb was the only insecticide
      that showed a high efficacy against F occidentalis at field dose rates.
      Acrinathrin and methamidophos were moderately effective, while endosulfan and
      deltamethrin were ineffective. Only moderate levels of resistance (Resistance
      Ratios at LC50 of 10-30) were detected for the selective insecticides methiocarb,
      formetanate and acrinathrin used against F occidentalis in crops where these
      insecticides are used intensively. This generalized and low level of resistance
      to these insecticides, coupled with a lack of efficacy for the three broad
      spectrum insecticides, was observed even in intensively managed vegetable crops.
      Implementation of IPM strategies in Murcia has contributed to more successful
      insecticide anti-resistance management.

PMID- 12233191
TI  - Quinoxyfen--resistance management and sensitivity monitoring in wheat: 1995-2000.
AB  - Wheat powdery mildew, Blumeria (= Erysiphe) graminis DC f sp tritici Marschal is
      one of the most important foliar diseases of cereals in Europe, and has shown a
      high potential for adaptability in sensitivity towards modern fungicides during
      the last 20 years. Quinoxyfen is a surface-mobile fungicide from a new chemical
      class that has been commercially used for the control of B graminis in Europe
      since 1997. When the compound was launched, a Resistance Management Strategy was
      implemented which included: no seed treatments, no autumn use, a specified window
      of application and recommendations for appropriate tank-mixing. To assess the
      success of this Management Strategy, a European-wide resistance monitoring
      programme was carried out between 1995 and 2000 using spore trap sampling, and a
      whole plant assay. The mean EC50 values found by year were 0.060 mg litre-1 in
      1995, 0.052 mg litre-1 in 1996, 0.071 ml litre-1 in 1997, 0.039 mg litre-1 in
      1998, 0.039 mg litre-1 in 1999 and 0.063 mg litre-1 in 2000. No new sensitivity
      classes were found. The slight shift to lower sensitivity in 1998 and 1999 was
      correlated with similar shifts in three wildtype isolates, and was ascribed to
      experimental variation. The monitoring programme will continue to assess the long
      term impact of the management recommendations on the resistance status of
      quinoxyfen.

PMID- 12233192
TI  - Analysis of insecticide-resistant Myzus persicae (Sulzer) populations collected
      in Italian peach orchards.
AB  - Several populations of the green peach aphid, Myzus persicae (Sulzer), were
      collected in the most important Italian peach-growing areas. In these
      populations, collected as primary colonies or as secondary ones, total esterase
      content and acetylcholinesterase sensitivity towards pirimicarb was assessed
      using biochemical assays. Most of the individuals analysed generally exhibited an
      elevated esterase content, and in some cases acetylcholinesterase insensitivity.
      The implications of resistance levels and distribution on M persicae control
      strategies are discussed.

PMID- 12233193
TI  - Activity of mesotrione on resistant weeds in maize.
AB  - Mesotrione is a new callistemone herbicide that inhibits the HPPD enzyme (p
      hydroxyphenylpyruvate dioxygenase) and introduces a new naturally selective tool
      into weed-management programmes for use in maize. Mesotrione provides control of
      the major broad-leaved weeds, and it can be used in integrated weed-management
      programmes depending on the grower's preferred weed-control strategy. At post
      emergence rates of 150 g AI ha-1 or less, mesotrione provides naturally selective
      control of key species that may show triazine resistance (TR), e.g. Chenopodium
      album L, Amaranthus species, Solanum nigrum L, as well as species of weed that
      show resistance to acetolactase synthase (ALS) inhibitors e.g. Xanthium
      strumarium L, Amaranthus spp and Sonchus spp. The data presented show that
      resistant and susceptible biotypes of these species with resistance to triazine
      herbicides, such as atrazine, simazine, terbutylazine and metribuzin, or ALS
      inhibitor herbicides, such as imazethepyr, remain susceptible to mesotrione.
      These results confirm that there is no cross-resistance in biotypes with target
      site resistance to triazine or ALS-inhibiting herbicides. It is important that
      herbicide choice and rotation becomes an integral part of planning weed
      management, so as to minimise the risks of crop losses from weed competition,
      build-up of weed seed in the soil and the further development of weed resistance
      across a range of herbicide modes of action.

PMID- 12233194
TI  - Docs win $7 million verdict in capitation dispute with HMO.

PMID- 12233195
TI  - Clinical integration model may offer new contracting option for IPAs, medical
      groups.
AB  - A California IPA recently completed a two-year journey that led to the early
      stage development of what is believed to be the first "clinically integrated"
      IPA. The new model allows the group to move away from capitation to FFS, but
      still negotiate collectively for its physicians.

PMID- 12233196
TI  - Online referrals one way capitated groups gain efficiencies, reduce errors.
AB  - An online referral system is just the latest money and time-saving tool in the e
      commerce arsenal at Hill Physicians Medical Group. Using a modified version of
      Healinx Corp.'s secure e-mail messaging platform, Hill is testing a custom-made
      online referral system at two primary care practices that appear to be helping
      the practice boost its bottom line under capitation.

PMID- 12233197
TI  - Report shows declines in HMO enrollment, capitation slowing.
AB  - Capitation losses appear to be leveling off. The decline in total HMO enrollment
      slowed in 2001 while Medicaid HMO enrollment grew for the 10th consecutive year.
      And despite a declining percentage of HMOs reimbursing primary care physicians
      and hospitals under capitation, the percentage of HMOs reimbursing some specialty
      physicians under capitation rose slightly, mirroring several other recent reports
      showing an increase in specialty cap.

PMID- 12233198
TI  - The economic model in theory.

PMID- 12233199
TI  - The importance of adequate length of antidepressant therapy.

PMID- 12233200
TI  - The SSRI therapeutic effective dose model.

PMID- 12233201
TI  - Goals and challenges of optimally treating depression in a managed care
      environment.

PMID- 12233202
TI  - Establishing the real cost of depression.

PMID- 12233203
TI  - Laboratory services regulations carry HIM implications.
AB  - This is Part 1 of a two-part article on national coverage and policies for
      clinical diagnostic laboratory services payable under medicare Part B. Part 1
      concentrates on the administrative policies. Part 2, which will appear in the
      October issue of the Journal, will focus on the national coverage policies
      developed for individual clinical diagnostic laboratory tests. For additional
      information regarding the new administrative policies, see the Centers for
      Medicare & Medicaid Services (CMS) Program Memorandum AB-02-030, which was issued
      to all Medicare contractors on March 5, 2002.

PMID- 12233204
TI  - United under HIPAA: a comparison of arrangements and agreements.

PMID- 12233205
TI  - On the horizon: a national healthcare information infrastructure.

PMID- 12233206
TI  - National healthcare information infrastructure.

PMID- 12233207
TI  - Documentation goes wireless: a look at mobile healthcare computing devices.
AB  - Patient care information often suffers as it travels from handwritten notes,
      dictation, or the memory of the clinician to the medical record. Hand-held
      devices equipped with mobile healthcare aplications can bring documentatin to the
      point of care. In this article, learn how mobile healthcare computing devices can
      decrease medical errors, increase efficiency, and improve the delivery of care.

PMID- 12233208
TI  - How the EHR transforms the HIM department: two stories. Document imaging,
      workflow restructure department.
AB  - HIM professionals have long known the electronic health record (EHR) will change
      the collection, storage, and maintenance of health information, not to mention
      the delivery of care, but what about the its effects on the HIM department? While
      revolutionizing the HIM process, there can't help but be major changes in the job
      descriptions, leadership, and even the physical layout of the department. In this
      article, learn how the implementation of the EHR transformed two HIM departments-
      for the better.

PMID- 12233209
TI  - Imaging system propels HIM department to EHR.

PMID- 12233210
TI  - HL7 standard shapes content, exchange of patient information.
AB  - NCVHS' endorsement of HL7 as the standard for electronic exchange of patient
      medical record information promises to simplify the transmission of such
      information between healthcare organizations. However, this endorsement also
      empowers HL7 to serve as the architect of the electronic health record. In this
      article, learn more about HL7 and what role can play in standards development.

PMID- 12233211
TI  - Transcription cost analysis reveals opportunities for savings, efficiencies.

PMID- 12233212
TI  - Practice brief. Maintaining a legally sound health record.

PMID- 12233213
TI  - ICD-9-CM committee presents new codes, changes.

PMID- 12233214
TI  - Change at hand: how PDAs can transform coding, billing.

PMID- 12233215
TI  - [Image of the month. Bourneville's tuberous sclerosis].

PMID- 12233216
TI  - [How I treat...advanced cancer of the pancreas with a novel approach directed
      against new targets].
AB  - A better knowledge of fundamental mechanisms of carcinogenesis allows the
      development of novel therapeutic tools specifically targeting the cancer cell.
      Our understanding of cellular and molecular mechanisms controlling cellular cycle
      and cell survival is an important step for new anti-cancer treatments. This
      review will focus on new therapeutic's strategies in advanced pancreatic cancer.

PMID- 12233217
TI  - [Clinical case of the month. Treatment of obstructive hypertrophic cardiomyopathy
      by percutaneous septal ablation].
AB  - Hypertrophic obstructive cardiomyopathy is a rare pathology characterized by the
      presence of an interventricular septal hypertrophy leading to an ejectional
      obstruction of the left ventricular outflow tract. Several therapeutic approaches
      have been proposed. Besides pharmacological and surgical (septal myomectomy or
      cardiac pacing) therapies, a more recent therapy is represented by a septal
      reduction obtained by percutaneous occlusion of the septal coronary branch
      supplying this myocardial segment. A clinical case leads to a review of the
      literature.

PMID- 12233218
TI  - [DHEA and rejuvenating intracrinology? Between reason and magic].
AB  - Slowing down ageing is a goal for a large part of the population. Some mercantile
      claims hold out bright prospects to DHEA. The effects of this hormone manifest
      themselves after intracrine conversion. In the skin, sebaceous glands enlarge and
      seborrhoea increases in post-menopausal women. No other effect is clinically
      discernable on the skin. At this level, DHEA does not show efficacy comparable to
      that of other anti-ageing compounds.

PMID- 12233219
TI  - [Hyperdense red blood cells and spherocytosis].
AB  - A 12-year old female, suffering from recurring episodes of icterus and abdominal
      pain, is hospitalized in emergency. She is not anemic but her hemogram reveals a
      high level of hyperdense red blood cells (32%; controls 0-2.5%) and an abnormal
      reticulocyte count (201 x 10(3)/microL; controls 29-84 x 10(3)/microL),
      indicating a 3.5 fold increase in RBC production. The same abnormalities are
      found in the patient's mother. The blood smear shows few spherocytes. RBC osmotic
      fragility is increased only after incubation. Hereditary spherocytosis is
      diagnosed following electrophoresis of membrane proteins which reveals a
      deficiency in band 3, a protein which links the lipid bilayer to the
      cytoskeleton. This case of hemolytic anemia-illustrates the physiopathologic and
      diagnostic significance of hyperdense RBC, which reflect the cell dehydration
      associated with the membrane disorder.

PMID- 12233220
TI  - [Prevention of type II diabetes by inhibiting the renin-angiotensin system].
AB  - Type 2 diabetes mellitus and arterial hypertension are part of the insulin
      resistance syndrome. Besides a metabolic component, insulin resistance has also
      an haemodynamic component, especially in relation with an endothelial
      dysfunction. Some studies suggested that inhibitors of angiotensin converting
      enzyme can improve insulin sensitivity. Interestingly enough, three clinical
      trials recently reported concordant results showing that the inhibition of the
      renin-angiotensin system significantly reduces the risk of developing type 2
      diabetes in patients at high risk of vascular complications, essentially with
      hypertension: the CAPPP trial with captopril (-14%, p = 0.39), the HOPE study
      with ramipril (-34%, p < 0.001) and the LIFE study with losartan (-25%, p <
      0.001). However, these observations could be criticized because such a protective
      effect was only considered as a secondary endpoint in these studies. Two large
      prospective, controlled, randomized, double-blind trials are ongoing to
      specifically confirm this interesting hypothesis, one with ramipril and the other
      with valsartan.

PMID- 12233221
TI  - [Arterial revascularization with free tissue transfer for salvage of ischemic
      limbs with extensive tissue loss: an alternative to amputation].
AB  - Severe limb ischemia is a common problem encountered in medical practice.
      Aggressive attempts at revascularization have extended the limits of limb
      salvage. However, in certain cases, extended tissue loss compromises the healing
      process. It often results in amputation despite bypass graft patency.
      Microvascular free tissue transfer combined with arterial revascularization
      allows healing of these wounds and limb preservation. This combined approach is
      the ultimate alternative to amputation.

PMID- 12233222
TI  - [Homograft mitral valve replacement].
AB  - The total homograft replacement of the left AV valve and subvalvular apparatus
      constitutes a delicate operation, which may prove beneficial in young patients
      with extensive bacterial endocarditis. The case of a staphylococcal endocarditis
      in a young drug addicted patient, operated three years previously of mitral valve
      repair for the same pathology, is presented. In addition to the complete excision
      of infected tissues and valvular substitution with biological material, this
      technique has the advantage of avoiding long term anticoagulation. The history,
      technical key points, and current indications of mitral homograft in the surgery
      of the left atrio-ventricular valves are reviewed.

PMID- 12233223
TI  - [Autism, TEACCH and Lovass methods: towards a synthesis].
AB  - Autism is a deficiency which remains controversial. Many therapies exist but none
      can really cure. Among different approaches, Lovaas and Teacch's are known in
      french speaking countries and seem antagonist. Some think they could be
      complementary. The purpose of this paper is to review this subject and prompt new
      thought and research.

PMID- 12233224
TI  - [Synovial metastases from colonic cancer presenting as arthritis of the knee.
      Characterization by 18FDG PET scan].
AB  - A case of carcinomatous monoarthritis involving the left knee due to colonic
      adenocarcinoma is described. Large recurrent synovial effusion, that will be
      later hematic, lytic lesion of the bones and chondrolysis were noted. Knee
      positron emitting tomography scan using FDG (FDG-PET) revealed a diffuse
      increased uptake in soft tissues assumed to be synovium, the hypertrophy of which
      was identified by ultrasonography. Whole body PET scan showed extensive lymph
      node, visceral and bone metastases, suggesting that the increase in the synovium
      could also be of metastatic origin. The final diagnosis of synovial
      carcinomatosis secondary to the known colonic adenocarcinoma was confirmed by
      histological analysis of biopsies obtained by arthroscopy. A review of the
      literature is realised. To our knowledge, this is the first synovial metastasis
      studied by FDG-PET.

PMID- 12233225
TI  - [How I investigate...a refractory hypertension].
AB  - Hypertension is a cardiovascular risk factor which needs a good evaluation before
      treatment. When this latter is decided, the target is to normalize high blood
      pressure. This requires a complete information of the patient; the latter will
      also receive individualized non pharmacological advices and, also, possibly
      different antihypertensive drugs. When blood pressure does not normalize, one
      must check the blood pressure measurement technique, the compliance to treatment
      and potential pharmacologic interferences. Secondary hypertension is only
      considered if resistance to therapy cannot be found. It should be remembered that
      obesity and sleep apnea disorders are responsible of many instances of refractory
      hypertension.

PMID- 12233226
TI  - [Clinical study of the month. The LIPS study: fluvastatin for prevention of
      cardiac events following percutaneous coronary angioplasty].
AB  - The prospective placebo-controlled LIPS study ("Lescol Intervention Prevention
      Study") demonstrated a significant cardiovascular protection by fluvastatin in
      patients with coronary artery disease (stable or unstable angina, silent
      ischemia), without major hypercholesterolaemia (135-270 mg/dl) following
      successful completion of their first percutaneous coronary intervention. When
      compared to the placebo group (n = 833), the fluvastatin group (n = 844) showed a
      relative risk reduction by 22% (relative risk: 0.78; 95% confidence interval:
      0.64-0.95; p = 0.01) of major adverse cardiac events after a median time of
      follow-up of 3.9 years. This effect is observed independently of baseline total
      cholesterol, of the presence of diabetes mellitus or the existence of multivessel
      disease. These results suggest that fluvastatin may favorably influence the
      restenosis process after percutaneous coronary intervention, even in the absence
      of severe hypercholesterolaemia.

PMID- 12233227
TI  - Improving employee comprehension. Eight tips for communicating information.

PMID- 12233228
TI  - Pressure ulcers. Two major concerns: involuntary weight loss and dehydration.

PMID- 12233229
TI  - Food and safety. Bioterrorism and our food supply.

PMID- 12233230
TI  - You are up to bat! Fourth base: home plate and a home run!

PMID- 12233231
TI  - OB/GYNs offer a rich source of referrals.

PMID- 12233232
TI  - Where do we go from here?

PMID- 12233233
TI  - Branding 101. It's time for healthcare to embrace this marketing mainstay.

PMID- 12233234
TI  - Facing the future.

PMID- 12233235
TI  - Are your patients satisfied?

PMID- 12233237
TI  - Boosting the bottom line with CRM.

PMID- 12233236
TI  - Measuring ROI: is it worth it? Interview by Richard K Thomas.

PMID- 12233238
TI  - Building on your quick wins.

PMID- 12233239
TI  - Minding your medical manners?

PMID- 12233240
TI  - The value of professional certification. Myth or reality?
AB  - Accountants do it. So do consultants, engineers, computer professionals, and
      public administrators. Fund-raising professionals do it too! What are all these
      professionals doing? They all participate in professional certification programs
      offered by leading professional associations. The Association for Healthcare
      Philanthropy (AHP) offers professional certification to its members through the
      Certified Fund Raising Executive (CFRE) Certification Board. The results of a
      2001 survey enlighten us on the true value of fund-raising certification.

PMID- 12233241
TI  - A new breed of donor. Trends in gift giving.
AB  - Let's say that as a result of a lot of hard work and personal sacrifice, you've
      accumulated a significant amount of money. Now you're looking for some charitable
      cause in which to invest. As you invest this money--money symbolizing the sum of
      your life's work--don't you wish to have some control, some degree of input into
      the manner in which the money is used? This attitude personifies today's newest
      type of donor.

PMID- 12233243
TI  - Join the team. One solution to the nursing shortage shows the importance of a
      positive attitude.

PMID- 12233242
TI  - HIPAA 101: stories from the field.

PMID- 12233245
TI  - An e-philanthro, update: are you ready for word of mouse?

PMID- 12233244
TI  - Get your organization in ship-shape.

PMID- 12233248
TI  - Doctors in a wired world: can professionalism survive connectivity?
AB  - The information revolution has the potential to reduce the asymmetry of
      information between patients and doctors and thereby to undermine a central
      pillar of physicians' claim to professional status: the possession of distinctive
      competence based on technical know-how selflessly applied and collectively
      monitored. A close analysis of the information revolution's likely effects
      suggests that for some patients with some conditions, their access to more and
      better information will indeed reduce the magic, mystery, and power of the
      medical profession. However, the information revolution also offers opportunities
      for physicians to bolster the cognitive and moral bases of professionalism. To
      seize those opportunities, physicians must master new roles and skills and avoid
      unacceptable conflicts of interest.

PMID- 12233247
TI  - Risky parental behavior and adolescent sexual activity at first coitus.
AB  - Data from the National Longitudinal Study of Adolescent Health (Add Health) were
      used to examine the impact of parents' behavior on adolescents' sexual experience
      and contraceptive use. All else being equal, adolescents whose parents engage in
      risky behaviors are especially likely to be sexually active and to have had sex
      before age 15. These findings are only partly attributable to the link between
      parents' risky behaviors (smoking, drinking, driving without seatbelts) and
      adolescents' risky behaviors (smoking, drinking, delinquent activity, association
      with substance-using peers). Although parental behaviors are effective predictors
      of adolescents' sexual activity, they are not effective predictors of
      contraceptive use or of method choice at first coitus. Overall, parents with low
      levels of self-efficacy seem to be especially likely to have children at risk of
      engaging in problem behaviors.

PMID- 12233246
TI  - Life course health development: an integrated framework for developing health,
      policy, and research.
AB  - The life course health development (LCHD) framework organizes research from
      several fields into a conceptual approach explaining how individual and
      population health develops and how developmental trajectories are determined by
      interactions between biological and environmental factors during the lifetime.
      This approach thus provides a construct for interpreting how people's experiences
      in the early years of life influence later health conditions and functional
      status. By focusing on the relationship between experiences and the biology of
      development, the LCHD framework offers a better understanding of how diseases
      occur. By suggesting new strategies for health measurement, service delivery, and
      research, as well as for improving health outcomes, this framework also supports
      health care-purchasing strategies to develop health throughout life and to build
      human health capital.

PMID- 12233249
TI  - Bargaining health benefits in the workplace: an inside view.
AB  - Before contract negotiations in 1999, the author served on an "issue-based"
      health benefits committee of faculty union representatives and university
      administrators. Although the committee solicited estimates from health insurers
      regarding the impact of higher copayments on monthly premiums, in subsequent
      negotiations, the projected cost savings did not lead to changes in coverage or
      copayments. The explanations offered are (1) national or regional employers may
      be reluctant to raise employees' health benefit copayments when labor markets are
      tight; (2) collective bargaining, particularly when other, nonmonetary issues are
      being bargained, may lead to results different from those from a strictly
      competitive model; and (3) employers with market power in the product market may
      shift these highest costs to consumers through higher prices.

PMID- 12233250
TI  - Teaching hospitals and quality of care: a review of the literature.
AB  - Because teaching hospitals face increasing pressure to justify their higher
      charges for clinical care, the quality of care in teaching and nonteaching
      hospitals is an important policy question. The most rigorous peer-reviewed
      studies published between 1985 and 2001 that assessed quality of care by hospital
      teaching status in the United States provide moderately strong evidence of better
      quality and lower risk-adjusted mortality in major teaching hospitals for elderly
      patients with common conditions such as acute myocardial infarction, congestive
      heart failure, and pneumonia. A few studies, however, found nursing care,
      pediatric intensive care, and some surgical outcomes to be better in nonteaching
      hospitals. Some factors related to teaching status, such as organizational
      culture, staffing, technology, and volume, may lead to higher-quality care.

PMID- 12233251
TI  - [Clinical and prognostic significance of seasonal factor in endogenous maniac
      states].
AB  - The study aimed at determination of clinical and prognostic significance of
      seasonal factor in endogenous maniac state development. Using clinico
      psychopathological and clinical follow-up study, 32 patients (30 women and 2 men)
      aged 20-50 years with seasonal endogenous mania were examined. Seasonal mania
      developed in 12 patients with bipolar affective disorder, in 13 patients with
      schizoaffective psychosis and 7 patients with attack-like schizophrenia (F31.1 -
      F31.6, F25 and F20.02 + F25 ICD-10 items respectively). Seasonal maniac state was
      shown to be a significant clinical symptom that might be regarded as a prognostic
      factor. In patients with bipolar disorder--with a prevalence of both mania and
      depression-seasonal mania development in autumn-winter period was a favourable
      prognostic trait, being observed mainly in manic depressive psychosis. In spring
      summer mania, prognosis was less favourable and was preferentially found in
      schizoaffective psychosis and attack-like schizophrenia.

PMID- 12233252
TI  - [The treatment of sleep disorders in opioid addicts].
AB  - Sleep disorders and hypnotic drug abuse in 112 opioid addicts were investigated.
      During intensive heroin use, regular or episodic benzodiazepines intake was found
      in 60.7% of the cases. The requirement for benzodiazepines in drug use may result
      from dissociated tolerance to opioids. Withdrawal insomnia was shown to develop
      in all the cases studied. The differentiation between objective and subjective
      requirements for hypnotics was carried out. The author suggests the term
      "hypnophilia". The interrelation between hypnophilia and higher anxiety is
      emphasized. Clozapine is a drug of choice in treatment of insomnia in opioid
      addicts.

PMID- 12233253
TI  - [The effect of some medications used in the treatment of cerebrovascular diseases
      on free radical oxidation in the model systems].
AB  - The effect of 5 medications used in the treatment of ischemic brain lesions on
      free radical oxidation was studied. The efficacy level was evaluated by
      chemoluminescent changes in the model systems generating active oxygen species
      and lipid peroxides radicals. The most active antioxidants inhibiting chemo
      luminescence proved to be mexidol, cavinton, instenon. Piracetam acts less
      effectively. Actovegin did not practically display any antioxidant activity.
      Thus, the medications studied have different effect on free radical oxidation,
      dysregulation of which underlies many neurological diseases i.e. ischemic blood
      circulation disorders.

PMID- 12233254
TI  - [The diagnostic significance of electrophysiological analysis of orientation
      reflex in hemispheric ischemic stroke].
AB  - Diagnostic significance of orientation reflex in response to neutral sound
      stimuli in hemispheric ischemic cerebral stroke is discussed. The following
      electrophysiological indices for orientation reflex were analysed:
      desynchronization reaction, non-specific vertex EEG potential and spontaneous
      electrodermographic activity--galvanic skin reflex to repeated sudden neutral
      audio stimuli were analysed. Beginning from the acute period of stroke, a follow
      up study was carried out. Correlations between stroke severity and orientation
      reflex stability as well as between a rate of some pattern diminution in the
      early rehabilitation period and hemispheric lateralization of the pathological
      focus and severity degree of the neurological deficit were found.

PMID- 12233255
TI  - [A complex of skull base and cervical spine anomalies and Chiari type I
      malformation].
AB  - To study a relationship between the skull base and cervical spine anomalies and
      Chiari type I malformation (CMI), 364 patients with CMI were examined using
      craniography and magnetic resonance imaging of the brain and spinal cord. To
      reveal bone anomalies and CMI, morphometric data analysis was performed. The
      control group consisted of 120 patients without central nervous system pathology,
      cranial and cervical spine anomalies. The data obtained allowed dividing the
      skull base and cervical spine anomalies identified in the CMI patients into 3
      groups: 1) primary anomalies (basilar invagination, platybasia, atlantal
      assimilation) predisposing to CMI development; frequent occurrence and reliable
      interrelation between these anomalies and CMI severity were found that confirmed
      the results reported in the literature on their key role in a small size of
      posterior cranial fossa; 2) combined with CMI bone anomalies, which do not
      influence CMI development (Klippel--Feil and Kimmerle anomalies); 3) secondary
      skull base and cervical spine deformations formed as a result of CMI impact
      (foramen magnum and cervical canal enlargement).

PMID- 12233256
TI  - [The changes of the function of lymphocytes natural killers in schizophrenics].
AB  - Cytotoxic activity and lymphocyte natural killers (NK) number as well as gamma
      interferon (gamma-IFN) production were studied in patients with paranoid (22
      patients) and progressive attack-like (39 patients) schizophrenia (47 male and 14
      female patients aged 16-62 years). Compared to controls, a decrease of NK
      activity and a trend towards gamma-IFN production decrease were found. In the
      patients, NK lymphocytes number was not changed. Cytotoxic activity was reduced
      only in the male patients, a frequency of cases with lower activity level being
      the highest in those with more severe form of paranoid schizophrenia. A
      significant difference of both indices was detected between men and women. In the
      men, the longer was the disease duration, the higher was cytotoxic activity and
      lymphocyte number increase. It was shown in vitro that monocytes are not involved
      in mechanisms changing the level of lymphocyte cytotoxicity in the patients and
      immune modulator enkad stimulats cytotoxic activity in the male patients.

PMID- 12233257
TI  - [Neurological symptoms in syphilis].

PMID- 12233259
TI  - [Hereditary spastic paraplegia].

PMID- 12233258
TI  - [A case of familial paroxysmal kinesic choreoathetosis].

PMID- 12233260
TI  - [Monoamine oxidase inhibitors: prospects for the use in clinical practice].

PMID- 12233261
TI  - [Neurobiological mechanisms of alcoholism (a review of a last decade
      literature)].

PMID- 12233262
TI  - [Mental disorders in patients with arterial hypertension with metabolic
      disturbances].
AB  - A battery of psychological tests has been used to study the psychic state and
      quality of life in 75 patients with mild and moderate arterial hypertension (AH)
      with or without (controls) different metabolic disturbances (diabetes mellitus,
      dyslipidaemia, obesity). Comparing to controls, the AH patients with metabolic
      disturbances suffered more frequently from different psychic disorders of
      neurotic register and their quality of life, general condition, activity and mood
      proved to be significantly worse. The authors conclude that psychological testing
      may be an important diagnostic tool in general hospital. It allows identification
      of the borderline mental disorders features, the correction of which appears to
      be of great importance for basic disease course and its therapy.

PMID- 12233263
TI  - [ECG diagnosis no. 1. What is your diagnosis? Atrioventricular block].

PMID- 12233264
TI  - [Autoimmune hepatitis and overlap syndrome: diagnosis].
AB  - Autoimmune hepatitis (AIH) is a rare autoimmune disease (incidence about 5% among
      all chronic liver disorders) that reflects a loss of tolerance to normal hepatic
      proteins. AIH is characterized by female preponderance, hypergammaglobulinemia,
      extrahepatic syndromes and a good response to immunosuppressive treatment. AIH
      may be subdivided into two or three subtypes. AIH type 1 is characterized by
      antinuclear autoantibodies (ANA) and/or smooth muscle antibodies (SMA). SMA are
      actin-specific, can occur without ANA and their presence relates strongly to AIH.
      AIH type 2 is defined by the presence of anti-liver-kidney microsomal antibodies
      (LKM-1). Patients with AIH type 2 are typically younger at the time of disease
      onset, exhibit higher inflammatory activity, suffer more frequent relapses under
      immunosuppressive treatment and are more likely to progress to cirrhosis. AIH
      type 3 is characterized by autoantibodies against the soluble liver antigen (SLA)
      and liver-pancreas antigen (LP), but ANA/SMA are frequently present and,
      therefore, some authors consider this autoantibody manifestation as belonging to
      AIH type 1. Antineutrophil cytoplasmic antibodies (ANCA) recognize cytoplasmic or
      nuclear components of neutrophilic granulocytes and are detected with high
      prevalence in patients with autoimmune liver diseases. They are associated with
      AIH type 1 but not with AIH type 2. However, 40-70% of patients with primary
      sclerosing cholangitis (PSC) also produce these autoantibodies. Autoimmune
      cholangitis is an idiopathic disorder with mixed hepatocellular and cholestatic
      findings that typically has antinuclear antibodies (ANA). It may be considered as
      an atypical form of primary biliary cirrhosis. It has been recognized that some
      forms of AIH may also occur with variable incidence and severity especially in
      patients with primary biliary cirrhosis (overlap AIH/PBC) or primary sclerosing
      cholangitis (AIH/PSC). On the basis of clinical, biochemical, serological,
      histological and radiological criteria a clear distinction between these
      conditions can be readily made in the majority of cases. An association of AIH
      typical autoantibodies (anti-LKM-1, anti-SLA/LP) in association with
      antimitochondrial autoantibodies (AMA) almost confirm the overlap syndrome
      AIH/PBC. In PSC patients expressing typical ERCP findings and suffering from
      inflammatory bowel disease (IBD), the diagnosis of an overlap syndrome between
      PSC/AIH can be readily made in the presence of ANCA and AIH relevant
      autoantibodies. Apart from this kind of overlap syndrome involving different
      types of autoimmune disorders within the liver AIH can be also associated with
      other organspecific autoimmune disorders as documented in the autoimmune
      polyglandular syndrome type 1 (APS-1). In this disease homozygosity for a defect
      in a single gene (AIRE) leads to a broad spectrum of organ specific autoimmune
      diseases.

PMID- 12233265
TI  - [Autoimmune hepatitis and overlap syndrome: therapy].
AB  - Autoimmune Hepatitis (AIH), primary biliary cirrhosis (PBC) and primary
      sclerosing cholangitis (PSC) represent acute and chronic inflammatory liver
      diseases in which immune reactions against host antigens are found to be the
      major pathological mechanism. Only for AIH there is evidence of an autoimmune
      etiology and humoral and cellular immune reactions are found directed against
      various liver cell antigens. By diverse autoantibodies several subgroups of
      autoimmune hepatitis can be distinguished. A very important disease promoting
      factor seems to be the genetically determined background for autoimmunity
      characterized by the HLA haplotype A1, B8 and DR3, respectively DR4. Although the
      histopathology of AIH shows no pathognomonic features distinguishing this type of
      hepatitis from virus induced chronic hepatitis there are some distinct
      characteristic morphological lesions. If untreated the prognosis of AIH is
      unfavourable but the benefit from immunosuppressive therapy with prednisolone and
      azathioprin is well established. In the last years there was increasing evidence
      for an overlap syndrome between AIH and PBC and rarely AIH and PSC. These
      patients are characterized by PBC characteristic bileduct lesions and oftenly
      antimitochondrial antibodies (AMA). They also show AIH typical inflammatory
      hepatic lesions in the periportal areas and portal tracts and oftenly the typical
      genetical background, the HLA haplotype A1, B8, DR3 or DR4. Most of these
      patients respond probably to a combination therapy containing prednisolon,
      azathioprine and ursodesoxycholic acid that leads to the reduction of the
      inflammatory activity.

PMID- 12233266
TI  - [Cholangiocarcinoma].
AB  - Cholangiocarcinomas (CCC) are rare tumors with an incidence of 2-4/100,000 per
      year. They are a heterogeneous group of neoplasias that include the most common
      perihilar or Klatskin tumor (60%), the intrahepatic (peripheral) CCC, the
      extrahepatic bile duct cancer, the gallbladder cancer and the cancer of the
      ampulla of Vater. At the time of diagnosis only 20% of patients can be treated by
      surgery, that offers the only chance for cure. Due to high recurrence rates liver
      transplantation is not indicated. Patients with advanced unresectable carcinoma
      have a dismal prognosis with an overall survival rate of only 6-8 months. Neither
      chemotherapy nor radiation therapy improves survival. In patients not eligible
      for curative surgery prevention or treatment of cholestatis is the main
      objective. This can be achieved endoscopically, percutaneously or by surgical
      biliodigestive anastomosis. Palliative chemotherapy results in response rates up
      to 20%. The most frequently used agents are 5-FU and Gemcitabine that can be
      combined with external or internal radiation. By combining different treatment
      modalities significant survival can be achieved in some patients. Evidence Based
      Medicine studies are needed before treatment strategies can be recommended for
      clinical practice.

PMID- 12233267
TI  - [Endoscopic polypectomy with the use of endoloop in giant gastric polyp: a case
      report].
AB  - The gastric polyps are lesions found in 2-3% of endoscopic procedures. We point
      out the hystologic nature of these lesions to a correct therapeutic evaluation.
      The endoscopic polypectomy is today safe; we report our experience in an
      endoscopic polypectomy with use of endoloop for a giant gastric polyp.

PMID- 12233268
TI  - Palivizumab in infants with gestational age < or = 28 weeks and bronchopulmonary
      dysplasia.
AB  - We report data from 11 patients < or = 28 weeks' gestation with severe
      bronchopulmonary dysplasia (BPD) prophylactically treated with palivizumab for
      prevention of respiratory syncytial virus (RSV) infection. All babies were
      receiving pharmacologic respiratory therapy at the moment of discharge from
      neonatal intensive care unit. Babies received 15 mg/kg i.m. palivizumab every 4
      weeks to a max of 5 doses during the period November-March. We compared them with
      8 similar infants that did not require therapy at discharge, nor were given any
      placebo. The treated infants did not present significant side effects. No baby in
      both groups was infected with RSV during the period of observation. We conclude
      from these preliminary data that palivizumab did not present contraindications in
      infants < or = 28 weeks' gestation with severe BPD requiring pharmacologic
      therapy at discharge. More data are required to evaluate efficacy to prevent RSV
      infection in these infants.

PMID- 12233269
TI  - Ectopic third molar in the condylar process: case report.
AB  - We describe an ectopic inferior third molar which is positioned in the condylar
      process and associated with an odontogenic cyst. The ectopic third molar is a
      quite frequent condition but it become unusual when the tooth is placed in the
      condylar region. In the reported case the removal of both the tooth and the cyst
      was recommended to solve the infective and articular symptoms and to prevent
      worse complications like pathologic fractures due to bone's absorption.

PMID- 12233270
TI  - [Simultaneous measurements of electrical coupling and action potential transfer
      in pairs of ventricular cardiomyocytes].
AB  - Spread and modulation of electrical activity in cardiac tissue requires
      intercellular transfer of current via gap junctions, specialised regions of
      densely packed ionic channels. Electrotonic interaction is determined not merely
      by intercellular electrical resistance (Rj) but rather by the interplay of Rj and
      sarcolemmal passive and active electrical properties (Zaniboni et al., Spitzer et
      al.). In this work we combined a well established protocol to measure Rj in cell
      pairs (Weingart e Maurer) with a stimulation protocol which allowed to
      simultaneously study parameters relative to action potential transfer during
      sequential stimulation. Current clamp experiments, performed on cardiomyocyte
      pairs held in double-patch configuration, allowed to simultaneously monitor, at a
      relatively high frequency (1 Hz), membrane resistance (Rm), resting potential
      (Vm), maximum depolarization rate (dv/dtmax) and time to peak of dv/dtmax in both
      cells as well as Rj. Spontaneous electrical uncoupling was observed in guinea pig
      cell pairs with little or no effect on action potential transfer. Pharmacological
      uncoupling with 40 microM beta-glycyrrhetinic acid reached, in one case, a much
      higher level of Rj and dramatically increased time delay for action potential
      appearance. When only Rj was measured over a short time interval after
      approximately two minutes from cell-attachments, values of Rj approximately 40 M
      omega in rat cell pairs (n = 20) and Rj approximately 15 M omega in guinea pig
      cell pairs (n = 24) were obtained. The possibility of monitoring simultaneously
      active and intercellular/cellular passive electrical properties makes this
      protocol particularly suitable to study dynamic changes in Rj during action
      potential transfer.

PMID- 12233271
TI  - [Osteochondroma. Report of a case with atypical localization and symptomatology].
AB  - Osteochondroma, the most common benign bone tumor, represents 10-15% of all bone
      tumors. It can occur frequently as solitary osteocartilagineous exostosis or
      rarely as hereditary multiple lesions. The most common sites of occurrence are
      long bones of the lower arm (50%), usually the lower end of the femur and upper
      end of the tibia. However, involvement of the small hand and foot bones occurs in
      10% of cases, pelvis in 5%, scapulae in 4%, and spine in 2%. Symptoms are not
      very specific. The authors present an atypical case of osteochondroma.

PMID- 12233272
TI  - Preliminary experience with a new osteosynthesis device for intertrochanteric
      fractures.
AB  - From 1999, at the Orthopaedic Clinic of the University of Siena, 56 patients were
      treated with the compression hip nail-plate system, a new synthesis device for
      the treatment of peritrochanteric fractures. The system consists in a new dynamic
      cephalic screw that could be combined with a plate or a femoral nail. The dynamic
      cephalic screw of the BCM system has a limited sliding method, impeding excursion
      greater than 10 mm and preventing excessive collapse of the fracture fragments
      that can evolve into a shortening of the limb. The canulated nail has a diameter
      of only 9 mm, which permits insertion into the shaft canal without reaming. The
      possibility of the double combination of the screw with a plate or with an
      intramedullary nail permits the surgeon to have a double solution with a single
      instrument at hand, and offers the opportunity of changing the choice of
      synthesis method to implant even during surgery.

PMID- 12233273
TI  - Crystalline aggregation in vitro: interaction between urinary macromolecules and
      the micromolecular environment.
AB  - The formation of calcium oxalate (CaOx) crystals, their growth and above all
      their agglomeration tendency are considered to be decisive factors in the renal
      stone formation. The aim of this study was to verify whether the formation in
      vitro of crystalline macroaggregates, induced by increasing loads of oxalate, is
      different in normal subjects as opposed to CaOx stone formers, free from urinary
      metabolic abnormalities. The possible interference of the urinary micromolecular
      environment on the activities of macromolecules with molecular weight greater
      than 10,000 Daltons was also evaluated. Formation of crystalline macroaggregates
      took place in controls at a relative CaOx supersaturation equivalent to 32.6 +/-
      12.9 and in stone formers at 34 +/- 12.3 (NS); the CaOx RS aggregation--CaOx RS
      nucleation delta was 11.4 +/- 12.2 in controls and 15.8 +/- 13.9 in stone formers
      (NS). Leaving aside the stone disease variable, the urine characterized by high
      baseline CaOx saturation, high ionic strength and high levels of citrate,
      magnesium and calcium, seemed particularly predisposed to macroaggregates
      formation; the opposite was true for urine characterized by a totally different
      micromolecular environment. A very close relationship was found between the CaOx
      RS aggregation--CaOx RS nucleation delta in urine filtered at 0.22 mu and in
      metastable solutions containing macromolecules in similar concentrations to those
      found in the native urine (r = 0.74, P < 0.0001). In conclusion the formation of
      crystalline macroaggregates in vitro does not present differences in normal
      subjects compared to CaOx stone formers free from urinary metabolic
      abnormalities. The urinary macromolecules seem to participate in the formation of
      the crystalline macroaggregates and their action seems to be affected by the
      urinary micromolecular environment and, even when they are re-suspended in a
      completely different medium, their action seems to be preserved intact.

PMID- 12233274
TI  - Healing of fresh tibial fractures with OP-1. A preliminary report.
AB  - Osteogenic proteins (OP) are elements of a class of natural growth factors called
      Bone Morphogenetic Proteins (BMP). A specific member of this class is OP-1, a
      human recombinant protein that has osteogenic properties. The osteoinductive and
      osteoconductive properties of OP-1, with its specific collagen matrix, promote
      the generation of new functionally active, biologically and biomechanically
      mature bone. We carried out a clinical study to verify the potential of this
      protein in fresh tibial closed fractures, using OP-1 associated with
      osteosynthesis by means of a monolateral external fixator.

PMID- 12233275
TI  - Percutaneous endoscopic gastrostomy after Billroth II gastrectomy.
AB  - Percutaneous endoscopic gastrostomy (PEG) is a valid alternative to surgical
      gastrostomy to provide nutritional support in patients unable to ingest food.
      Previous Billroth II gastroresection is no longer a contraindication. We describe
      our experience with 5 cases of PEG placement in patients who had previously
      undergone Billroth II gastroresection.

PMID- 12233276
TI  - Hypercalcemia due to ectopic secretion of parathyroid related protein from
      pancreatic carcinoma: a case report.
AB  - This case is a report of a male, 52 year old, heavy smoker, with a history of
      about 10 years of alcohol abuse (he quitted in 1993), gastric resection for ulcer
      (Billroth II 1970), hypoparathyroidism and macroamylasemia, died for undiagnosed
      pancreatic carcinoma revealed at necroscopy. The only clinical evidence of
      carcinoma were pulmonary metastasis and paraneoplastic syndrome characterized
      from hyponatriemia due to inappropriate secretion of antidiuretic hormone and
      elevation of seric calcium caused by parathyroid hormone related protein. In
      patients without endocrine abnormalities, such unusual paraneoplastic syndrome
      could cause hypercalcemia, but in our patient, the increased calcemia did not
      reach abnormal levels due to the previous hypoparathyroidism. At present time,
      there are no clinical reports of parathyroid related protein secretion by
      pancreatic carcinoma and therefore, it could speculate that this modification
      together with ectopic secretion of antidiuretic hormone, represent a peculiar
      evidence of otherwise unknown and undetectable pancreatic carcinoma.

PMID- 12233278
TI  - [Your ultrasound diagnosis? Hemangiosarcoma of the spleen].

PMID- 12233277
TI  - The CLOS MB intramedullary nail for the treatment of pathological femoral shaft
      lesions.
AB  - Advances in systemic and radiation therapy have led to considerable improvement
      in the prognosis of patients with metastatic disease. As a result, orthopedic
      surgeons are being asked with increasing frequency to evaluate and treat the
      manifestations of skeletal metastases. Intramedullary nailing is a valuable
      technique for stabilizing (impending) pathological femoral fractures or
      osteolytic lesions. From January 1999 to January 2001 we treated 5 patients for
      skeletal metastases in the diaphyseal region of the femur. One month after
      surgical stabilization of the pathological lesion involving the femur, we
      observed significant improvement in quality of life, including pain relief and
      early ambulation.

PMID- 12233279
TI  - [Hepatocellular carcinoma: risk groups--screening].
AB  - Cirrhosis of the liver has to be regarded as a premalignant condition independent
      of its etiology. The annual risk of developing HCC in cirrhosis is between 1% and
      6%. Surveillance-programs have been introduced to detect early stages of HCC in
      order to improve mortality. However, only controlled trials will answer the
      question of the efficacy of such programs. Studies on the potential benefit of
      surveillance-programs comparing survival in surveilled and unsurveilled patients
      are so far lacking. It seems clear, however, that surveillance-programs can
      detect small tumors, often unfocal and potentially treatable by a curative
      approach. Moreover, the etiology (HBV, HCV, genetic hemochromatosis) and activity
      of liver cirrhosis as measured by serum-transaminases, liver histology (small
      cell dysplasia and atypical regenerative nodules), Child-Pugh-stage and the
      concentration of alpha-fetoprotein at the beginning of a surveillance-program-
      all these factors reflect a high risk of developing HCC in an individual patient.
      Until programs are introduced on the basis of randomized, controlled trials of
      surveillance vs. usual care (with liver-related, specific deaths and all-cause
      mortality as end-points) it seems reasonable to screen high-risk patients semi
      annually by liver ultrasound and determination of AFP-concentration in the serum.

PMID- 12233280
TI  - [Nonsurgical therapy of hepatocellular carcinoma].
AB  - Several non-surgical local ablation methods for the treatment of hepatocellular
      carcinoma (HCC) have been developed. Among them, percutaneous ethanol injection
      is worldwide an accepted alternative to surgery in patients with small HCCs.
      Other local minimal-invasive treatment options, like one time radio-frequency
      thermal ablation seem to result in more effective tumor control. Randomized
      controlled trials showed no survival benefit after transarterial
      chemoembolization and its variants for the treatment of local advanced HCCs.
      Combined therapeutic strategies may play an increasing role in future in these
      cases. Effective chemotherapy is not available for metastasized or advanced HCCs.
      The role of novel techniques for the treatment of HCC has to be carefully
      determined in large controlled clinical studies.

PMID- 12233281
TI  - [Prevention of hepatocellular carcinoma].
AB  - Prevention is an increasingly important area of modern medicine. One of the
      foremost goals in the field of hepatology is prevention of hepatocellular
      carcinoma since this tumor has a poor prognosis and current therapeutic options
      are limited. Most hepatocellular carcinomas arise from chronic liver disease and
      liver cirrhosis which is considered a major risk factor for tumor development.
      The most common etiologic factors causing liver cirrhosis include chronic viral
      hepatitis, alcohol consumption, toxins and a few metabolic disorders. This review
      discusses current therapeutic concepts for prevention and treatment of chronic
      liver disease and cirrhosis.

PMID- 12233282
TI  - [Liver transplantation in hepatocellular carcinoma: new developments].
AB  - Today, liver transplantation is the only simultaneous treatment of cirrhosis as
      well as of HCC. A crucial factor for outcome after liver transplantation is the
      appropriate selection of patients. Tumor diameter and node number in correlation
      with the histopathological grading are used as surrogate markers to predict the
      prognostically relevant vascular invasion. Many centers accept patients suffering
      from a HCC with a maximum diameter of 5 cm and up to 3 tumor nodes. Total
      hepatectomy and liver transplantation for patients suffering from small
      hepatocellular carcinoma in cirrhosis result in 5- and 10-year-survival rates of
      70% and 60%, respectively. This result reflects low rates of postoperative
      mortality and tumor recurrence as well as a decreased mortality due to the
      underlying cirrhosis. In multivariate analyses, vascular invasion and
      histopathological grading were significant risk factors for patient survival.
      Histopathological grading was also identified as most important risk factor for
      vascular invasion.

PMID- 12233283
TI  - Clinical effectiveness of a new vaginal contraceptive cream: a preliminary
      report.

PMID- 12233285
TI  - Vas deferens anastomosis: a review of the literature and a report of three
      consecutive cases.

PMID- 12233286
TI  - Sterilization at the New York Hospital over a twenty year period, 1932 to 1952.

PMID- 12233288
TI  - A vaginal jelly alone as a contraceptive in postpartum patients.

PMID- 12233289
TI  - Vanderbilt cooperative study of maternal and infant nutrition.

PMID- 12233290
TI  - Conception control by plastic cervix cap.

PMID- 12233291
TI  - The induction of sexual maturity in the genitally hypoplastic adult.

PMID- 12233297
TI  - All you want to know about the pill.

PMID- 12233307
TI  - Comments on the Medical Tribune series on sterilization.

PMID- 12233310
TI  - Haitian government and private centre cooperate to provide family planning
      services and education.

PMID- 12233328
TI  - Premarital information efforts under way.

PMID- 12233330
TI  - [Contraception in diabetic women].

PMID- 12233342
TI  - Survival of mankind: the population viewpoint.

PMID- 12233352
TI  - Participatory pop-ed wins widening favor.

PMID- 12233353
TI  - PGH Training Centers helps institutionalize surgical sterilization in Philippine
      program.

PMID- 12233355
TI  - Thai nurses' family planning project expands into nationwide service program.

PMID- 12233377
TI  - Counseling the abortion patient: a pastoral perspective.

PMID- 12233378
TI  - Time to learn, time for a better life -- the Women's Education Project in Upper
      Volta.

PMID- 12233379
TI  - A regional approach to women's needs: the Women and Development Unit in the
      Caribbean.

PMID- 12233380
TI  - Introduction: some facts and figures.

PMID- 12233381
TI  - Social and economic factors affecting women's health.

PMID- 12233382
TI  - Yes to breast feeding, but...how?

PMID- 12233383
TI  - The special hardships of disabled women.

PMID- 12233384
TI  - The condition of women and children's well-being.

PMID- 12233385
TI  - How female education reduces fertility: models and needed research.

PMID- 12233386
TI  - Effective ways to communicate family planning: cases and strategies.

PMID- 12233387
TI  - Singapore: population.

PMID- 12233404
TI  - New report on statistical disclosure.

PMID- 12233405
TI  - 1980 census data products and coverage improvement.

PMID- 12233406
TI  - The 1980 census questionnaires.

PMID- 12233407
TI  - Standardizing population projections required in federal fund allocations.

PMID- 12233408
TI  - The metropolitan statistical area classification: final standards for
      establishing metropolitan statistical areas following the 1980 census.

PMID- 12233409
TI  - The "population problem" in the South Pacific. In 2 parts.

PMID- 12233410
TI  - A review of some of the major statistical agencies within the U.S. federal
      statistical system.

PMID- 12233412
TI  - Statistical work in new China.

PMID- 12233413
TI  - Documents relating to the metropolitan statistical area classification for the
      1980's.
AB  - "This statement provides background information on the metropolitan area concept
      and the development of the official standards for defining metropolitan
      statistical areas for [U.S.] Federal statistical purposes. It discusses each
      section of the new standards and points out how the new provisions differ from
      those previously in effect."

PMID- 12233415
TI  - [Publishing plan for population statistics and general elections 1980].

PMID- 12233419
TI  - Law and its impact on family formation and family size in Sri Lanka.

PMID- 12233421
TI  - [The Polish family in the light of the 1978 national census].

PMID- 12233422
TI  - Law and its impact on family formation and family size in Sri Lanka.

PMID- 12233423
TI  - [Survey program of the population census in 1980].

PMID- 12233424
TI  - [Regional differences in life expectancy].

PMID- 12233425
TI  - [The population of La Mancha in the sixteenth and seventeenth centuries].

PMID- 12233426
TI  - [On the aged population:  with regard to the Year of the Elderly].

PMID- 12233427
TI  - [Motivation with regard to attitudes toward procreation among married women].

PMID- 12233428
TI  - New Granadan native populations:  recent demographic research.

PMID- 12233431
TI  - The growth of urban population in the Philippines:  1975-1980.

PMID- 12233432
TI  - [The weight of immigration in Saudi Arabia].

PMID- 12233435
TI  - Population distribution and quality of life in the Taiwan area.

PMID- 12233437
TI  - Presidential address.

PMID- 12233438
TI  - Convocation address.

PMID- 12233439
TI  - Director's report.

PMID- 12233464
TI  - Urbanization processes and policies in Africa: lessons from Kenya, Tanzania,
      Zambia and Zimbabwe.

PMID- 12233468
TI  - A modified probability distribution for first birth interval.

PMID- 12233471
TI  - Beyond survival: children's growth for national development.

PMID- 12233472
TI  - Progress review of the child survival and development revolution 1983-1986.

PMID- 12233477
TI  - [The Italian migration chain: some thoughts on aspects of the Argentine case].

PMID- 12233478
TI  - Associative strategies against geographical uprooting and social isolation.

PMID- 12233479
TI  - Australia:  the coming of age.
AB  - Current demographic trends in Australia and their implications are assessed.  The
      author concludes that "Australia faces a relatively favourable demographic
      future:  ageing is proceeding at a slower pace here, the pattern of the labour
      force ageing is conducive to restructuring in the intermediate future, and a well
      established immigration policy can be used to accommodate demographics with
      social and economic goals.  The financing of social services for the aged will
      produce fewer concerns here partly because of less immediate demographic
      pressures and partly because of the orientation of the age-pension system."

PMID- 12233486
TI  - [Youth mortality in Poland].

PMID- 12233488
TI  - Black suburbanization in the mid-1980s:  trends and differentials.
AB  - "The 1980 U.S. Census revealed a marked acceleration in the suburbanization of
      blacks during the 1970s.  This paper provides a preliminary answer to whether
      that acceleration continued in the 1980s by examining the 1985 American Housing
      Survey (National and Metropolitan Samples).  These data sets permit racial and
      socioeconomic status comparisons in overall suburbanization level and in the
      propensity of recent movers to choose suburban destinations.  Blacks continue to
      exhibit low levels of suburbanization relative to whites, and only a small
      percentage of blacks originating in central cities move to suburban areas. 
      However, once in the suburbs, blacks tend to remain there at the same rate as
      whites.  Intrametropolitan racial segregation remains strong, although it shows
      signs of decreasing."  This paper was originally presented at the 1990 Annual
      Meeting of the Population Association of America (see Population Index, Vol.  56,
      No. 3, Fall 1990, p. 431).

PMID- 12233489
TI  - [Population and employment in Latin America].
AB  - Both high rates of labor force growth and large dependency ratios are forecast in
      this paper for the countries of Latin America in the 1990s. The author concludes
      that "population and employment problems must be given high priority in bilateral
      negotiations and/or with international organizations when deciding upon
      structural adjustment strategies." (SUMMARY IN ENG)

PMID- 12233490
TI  - Thai family demography:  a review and research prospects.
AB  - "This paper attempts to give an overview of demographic knowledge on the Thai
      family and to suggest directions for future research."  Aspects considered
      include marriage, marital disruption, household size and structure, headship,
      flexibility of Thai family structure, the family life cycle and inheritance
      patterns, and the impact of social change. (SUMMARY IN THA)

PMID- 12233491
TI  - [[The population of Thailand after the reproductive revolution]].
AB  - The "population of Thailand is one among the few population groups in [modern
      times] which has experienced [a] rapid decline in fertility level within two
      decades.  Thailand's population completed the reproductive revolution process so
      quickly that its age structure has not had time to adjust and still holds the
      potential for growth for several decades to come.... During the period of
      reproductive revolution from 1970 to 1990, the population increased by 20
      million.... As for the effect of reproductive revolution on the age structure of
      the population, the pattern is that the proportion of children (under 15 years of
      age) declines while the number and proportion of population in working-age group
      (15-59 years of age) and the elderly (60 years and over) tend to increase.... The
      reproductive revolution also results in a number of positive economic and social
      implications such as a higher per capita income, [a larger] work force, a gradual
      reduction in the number of new entrants into the labour market and the decrease
      in the number of school age population." (SUMMARY IN ENG)

PMID- 12233492
TI  - [[Population and industrial development]].
AB  - "Concurrent with the decline in population growth rate in the 1980s, Thailand
      experienced an unprecedented rate of economic growth....Such phenomenal economic
      growth has generally been attributed to the internationalization of the Thai
      economy through the rapid expansion of exports, foreign investment and tourism. 
      However, industries in the manufacturing sector...tend to be resource-based and
      labour-intensive.  Moreover, foreign investment in export-oriented industries
      tends to use Thailand as a base for assembling rather than producing goods and
      has been attracted primarily by cheap labour cost.  All these may contribute to
      the employment of [a] nonskilled, lowly-paid labour force, but not the
      development of scientific/technology based industries, the foundation for
      permanent and lasting economic development." (SUMMARY IN ENG)

PMID- 12233494
TI  - [Epidemiologic crisis in Hungary].

PMID- 12233497
TI  - [Population policy in Thailand].
AB  - Population policy may be defined differently by students of demography but it is
      generally defined as measures aiming at influencing demographic processes-
      fertility, mortality, and migration--through public and private programs.
      Population policy may also be classified into different types: direct and
      indirect policies; population influencing and population responsive policies;
      explicit and implicit policies; and domestic and international policies. For
      Thailand, earlier population policies tended to be policies aimed at increasing
      the size of population through pronatalist and public health measures. However,
      findings of various studies in the early 1960s indicated that the rate of
      population growth in Thailand since the end of World War II had been as high as
      3% per annum. These had led the government to eventually issue the first national
      population policy statement "supporting family planning through a voluntary
      system..." in March 1970. The first 5-year family planning program was included
      in the health plan of the Third National Economic and Social Development Plan
      (1972-1976). From the Fourth National Economic and Social Development Plan (1977
      1981) onwards, population policies were made more comprehensive to cover all
      dimensions of population: population growth; quality of population; and
      population distribution and human settlements. Since population policy is an
      integral component of overall economic and social policies, conflicts between
      objectives of sectoral policies have to be minimized as much as possible. Future
      options of the population policies were briefly discussed.

PMID- 12233498
TI  - [[A critical period in the evolution of the population of Thailand]].
AB  - "The paper, based on population projections for Thailand...examines the growth
      and the structure of the Thai population between 1990 and 2115.  The projections
      are prepared on the basis of the sex and age distribution of the 1990
      population.... The study concludes that in order to maintain...economic and
      social prosperity, security and [prevent] the eradication of the Thai race, the
      government will have to raise fertility of the population at least up to the
      replacement level." (SUMMARY IN ENG)

PMID- 12233500
TI  - Constitution of the Republic of Kazakhstan [28 January 1993].

PMID- 12233501
TI  - [An optimum population for Thailand].
AB  - "In Thailand to date, the systematic analysis to determining an appropriate size
      of the population using economic, social, political and cultural criteria has not
      been attempted, let alone conducting a research on an optimum population. What
      have been made to date are analyses indicating that the rate of population growth
      at certain [periods] tends to be too low or too high...thus leading to the policy
      to increase or reduce the rate of population growth. Difficulties in determining
      an optimum population [are] due to the dynamic nature of population development
      and the fact that all other factors affecting the welfare of population are
      always changing, [thus] it is not cost effective to conduct research for
      determining an optimum population for the purpose of policy formulation."
      (SUMMARY IN ENG)

PMID- 12233502
TI  - Some recent demographic developments in Ireland.

PMID- 12233503
TI  - Level of awareness about AIDS: a comparative study of girls of two senior
      secondary schools of Chandigarh.

PMID- 12233506
TI  - [Publications by authors affiliated with the School of Medicine, University of
      Puerto Rico: 1950-2000. I].

PMID- 12233505
TI  - [Why belong to an HMO?].

PMID- 12233516
TI  - [Population in the macro-econometric models of French planning].

PMID- 12233517
TI  - [Demographic trends and housing].

PMID- 12233518
TI  - [Main lines of evolution of the French population since World War II].

PMID- 12233519
TI  - [Duration and quality of life of the elderly population.  Toward a simultaneous
      consideration of mortality and incapacity in the forecasting of health needs].

PMID- 12233520
TI  - [In search of a population effect in the growth of the public function (1952
      1983)].

PMID- 12233521
TI  - [The influence of economic variables on marital fertility in France from 1959 to
      1981:  an attempt at evaluation according to birth order].

PMID- 12233522
TI  - [Economic activity and female life expectancy].

PMID- 12233524
TI  - [Demographic trends and the burden of financing retirement].

PMID- 12233523
TI  - [Demographic factors in the evolution of unemployment].

PMID- 12233526
TI  - [Tubal sterility operation with the aid of an operating microscope].

PMID- 12233527
TI  - Antecedents of early marital and fertility behavior: the effects of social
      origins and adolescent attitude formation.

PMID- 12233539
TI  - U.S.S.R.

PMID- 12233540
TI  - Indonesia.

PMID- 12233541
TI  - Ghana.

PMID- 12233589
TI  - From the countryside to the cities:  a comparative historical analysis of rural
      urban migration in Russia and in the Soviet Union during the industrialization
      drive.

PMID- 12233599
TI  - A study of vasectomy camps in industrial sector.

PMID- 12233600
TI  - A case study of district mobile health care team.

PMID- 12233602
TI  - Some field problems in follow-up surveys: a study of IUD acceptor.

PMID- 12233601
TI  - Effectiveness of auxiliary nurse midwife in delivering MCH service.

PMID- 12233603
TI  - Some guidelines for sub-centre supervision in F.W.  Programme.

PMID- 12233604
TI  - Socio-demographic and professional profile of trained indigenous dais.

PMID- 12233605
TI  - The role of planned and systematic supervision in the F.W. performance.

PMID- 12233606
TI  - [Legal and demographic aspects of terminating pregnancy and using
      contraceptives].

PMID- 12233607
TI  - [Special issue on a conference held at the Institute from November 29- December
      12, 1976].

PMID- 12233608
TI  - [Religion and family planning: the family, formation, relations, procreation].

PMID- 12233609
TI  - [Values: between development and population growth. A socio-anthropological
      study].

PMID- 12233610
TI  - [Research on internal migration in Egypt: a critical review].

PMID- 12233611
TI  - [Social organization strategies and family planning decision making in low-income
      families].

PMID- 12233612
TI  - Egypt: conflicting decree on FGM.

PMID- 12233613
TI  - [From slave trade to environmental crisis: a viewpoint].

PMID- 12233614
TI  - [A demographic analysis of East Africa].

PMID- 12233615
TI  - Demographic change, international migration, and public education.
AB  - "This paper studies the impact of demographic change and international migration
      on economic development and the education sector. We employ a simple simulation
      model for tracing the impact of international migration on the educational and
      economic system, under alternative assumptions on the education background and
      adaptation costs of migrants. An application to the case of the Netherlands shows
      that international migration of whatever (realistic) level will not be able to
      prevent strong population aging during the period 2010-2035. Given the current
      below-average educational and productive profile of the immigrant population in
      the Netherlands, increased migration will only make matters worse."

PMID- 12233616
TI  - A model of the impact of immigration on health and social service expenditures
      for the elderly.
AB  - "Immigration, primarily from the former Soviet Union, has swelled the population
      of Israel by 10% between 1990 and 1993 and total population growth by the end of
      the decade is expected to be over 30%. The research presented here represents
      part of a larger effort to project needs and costs for the entire population in
      order to assist health and social welfare services in planning and resource
      allocation. The paper presents an overview of the current demographic situation
      in Israel, a theoretical model for estimating the growth in needs, and estimates
      of needs and costs for services for the elderly population based upon this
      model."

PMID- 12233617
TI  - Demographic characteristics and the public bundle.
AB  - "This paper explores the relationship between the demographic characteristics of
      a community and the quantities of goods and services provided by its government,
      what we label the ?public bundle'. We consider three models of public
      spending.... To evaluate these models of spending, we examine how county and
      state spending in the United States is affected by the age and racial
      composition, and the total size of a jurisdiction. We find that the estimated
      effects of demographic characteristics in the state equations are strikingly
      different from the estimated effects in the county equations. One possible
      explanation for these differences is that a jurisdiction's spending is affected
      differently by its own demographic characteristics and by the characteristics of
      the surrounding area. We conclude that community preference is important in
      explaining local spending, but that its determination is more complex than simple
      theory suggests."

PMID- 12233618
TI  - The aging of the population and the financing of local governments.
AB  - "This paper explores the residential property tax burdens faced by elderly
      homeowners in the United States. The results demonstrate that the use of annual
      data in income and property tax liabilities to calculate tax burdens overstates
      the regressivity of the property tax.  The magnitude of the bias created by using
      annual income is determined by comparing tax burdens calculated from annual data
      with burdens calculated from tax liabilities and income data covering a 12-year
      period. The results indicate that while the residential property tax on the non
      elderly is approximately proportional, the pattern of burdens on the elderly
      remains regressive."

PMID- 12233619
TI  - On the role of budgetary policy during demographic changes.
AB  - "The paper investigates the relationship between old age income maintenance and
      budgetary policy when a growing proportion of the population is retired. Special
      attention is paid to the different kinds of adjustment required under pay-as-you
      go (PAYG) and fully-funded (FF) pension schemes. The paper shows that FF schemes
      reach spontaneously a new equilibrium while PAYG systems need policy action. With
      reference to PAYG systems, the paper shows that the tax increase called for by
      most governments is appropriate in the short-run, when the dependency ratio plays
      a dominant role. In the long-run, however, the increase in the tax rate is
      smaller, as the effects of the changes in the dependency ratio is offset by the
      lower need of public savings required for financing capital accumulation." The
      geographical focus is on developed countries.

PMID- 12233620
TI  - Demographics and debt service.
AB  - "The discussion on the effects of the ongoing demographic transition on
      government behaviour has never mentioned its likely effect on an expenditure item
      (apparently non age specific) such as the debt service. This paper attempts to
      show that such effects could be non-negligible in countries (such as most
      European countries) where social security wealth arises from mandatory
      participation in pension schemes."

PMID- 12233621
TI  - Implications of economic transition and demographics for financing pensions in
      the former socialist economies.
AB  - "This paper is concerned primarily with the financing of pensions, or the old-age
      income maintenance portion of the social security system.  While the discussion
      here will be limited to Hungary and Poland, most of the post-socialist countries
      of East and Central Europe and of the former Soviet Union face similar problems."
      The author suggests "a set of alternative pension financing strategies....A novel
      approach is to replace the payroll tax with part of a value-added tax, which may
      be a good short run solution to current financial crises of the pension systems
      in these countries."

PMID- 12233622
TI  - Aging, intergenerational distribution and public pension systems.
AB  - "This paper develops an intertemporal simulation model capable of addressing the
      macroeconomic and distributional effects of demographic shocks in a small open
      economy. Two sources of population aging are examined, viz. lower birth rates and
      prolonged expected lifetimes at retirement age. Due to strong expectational
      effects, both shocks are found to change average consumption in a downward
      direction, in the short run as well as in the long run. This effect is matched by
      a strong net acquisition of foreign assets. Furthermore, it turns out that the
      intergenerational distribution of the burden of adjusting to an aging population
      is strongly dependent on whether the benefit rate, the contribution rate, or the
      relative non-capital income of pensioners and workers is held fixed."

PMID- 12233623
TI  - Demographics, political power and economic growth.
AB  - "Growth theory may be used to predict the response of saving, capital formation,
      and output growth to large demographic shifts. Such large shifts would also be
      expected to alter the demand for government services and the desired levels of
      taxation in the population. This paper extends the overlapping-generations model
      of economic growth to predict the evolution of government tax and spending policy
      through the course of a major demographic shift. Simulations suggest that this
      approach may yield valuable insights into the evolution of policy in the United
      States and other industrialized economies."

PMID- 12233624
TI  - Poverty, demographic characteristics and public policy in CIS countries.
AB  - "The demographic characteristics of different regions in the former Soviet Union
      influence the nature of poverty in the newly successor independent states....
      Despite a common policy inheritance, major adjustments are needed in the major
      social protection instruments to reflect differences in demographics along with a
      changing resource base."

PMID- 12233625
TI  - Infant mortality and public policy.
AB  - "Arguing that conventional indices of poverty (such as the head-count ratio) do
      not capture all aspects of deprivation that large segments of the population
      experience in developing countries, the present paper concentrates on progress in
      reducing infant and child mortality, and the underlying factors. The role of
      public policy in reducing infant and child mortality is emphasised. While income
      matters, (independently) aspects of maternal care and access to certain basic
      health services also have a significant role. In particular, female literacy (as
      a proxy for mother's literacy) has a substantial negative effect. In the context
      of the concern for cost-effectiveness of public expenditure during structural
      adjustment, a case is made for reordering of priorities in educational and health
      expenditure, and for specific policy interventions designed to promote female
      literacy."

PMID- 12233626
TI  - Demographics and social security.
AB  - "This paper considers the welfare implications of the interactions between
      demographic changes and social security in an overlapping generations model in
      which retirement decisions are endogenous. Both a pay-as-you-go system and an
      actuarially-fair system are examined." The geographical focus is on the United
      States.

PMID- 12233627
TI  - Public pensions and declining fertility in a small open economy: an intertemporal
      equilibrium approach.
AB  - "The aging of the population in several industrial countries has raised concern
      about the financing of pay-as-you-go public pension schemes.  This paper employs
      a numerical applied general equilibrium model of the Netherlands to explore how a
      unilateral temporary decline in fertility affects a small open economy. It
      focuses on intergenerational distributional effects as well as on macroeconomic
      consequences for employment, saving, investment, and external trade and capital
      flows.  Furthermore, it discusses several policy options involving the public
      pension schemes to cope with the intergenerational distributional and
      macroeconomic effects of the decline in fertility."

PMID- 12233628
TI  - [Special section on the All-Union population census].

PMID- 12233629
TI  - [Statistical materials.  Results of the 1985 socio-demographic sample survey of
      the population].

PMID- 12233630
TI  - [Calculating urbanization levels for miro-regions].

PMID- 12233631
TI  - [Shifts in the distribution of population in the USSR].

PMID- 12233632
TI  - [Population geography in the USSR on the sixtieth anniversary of the Soviet
      state].

PMID- 12233633
TI  - [Urbanization in the USSR:  problems of spatial organization].

PMID- 12233635
TI  - [Regional population forecasts and ethnic processes].

PMID- 12233636
TI  - [Problems of population formation in the BAM (Baikal Amur Mainline) zone].

PMID- 12233637
TI  - [The present phase of development of million-population cities in Western
      Europe].

PMID- 12233638
TI  - [The spatial evolution of urbanization in the Socialist countries of Europe].

PMID- 12233639
TI  - The International POPLAB Program: a review.

PMID- 12233645
TI  - A modified logistic model applied to human populations.
AB  - "The use of the logistic curve for forecasting human populations [in the United
      Kingdom] considered by Leach is re-examined.  A modification of the use of the
      logistic curve is suggested, which changes the emphasis from fitting a logistic
      trend to providing a forecast logistic trend.  The assumption, used by Leach,
      that the variance of the additive disturbance term is constant is replaced by a
      more realistic supposition that the variance of the proportional disturbance is
      constant.  The forecasting performance of the modified logistic model is shown to
      be superior to that of the model used by Leach."  A reply by Leach (pp. 496-7)
      and a response by the author (p. 498) are included.

PMID- 12233646
TI  - The use of sigmoids in modelling and forecasting human populations.
AB  - "The aim of this paper is to present a review that might justify giving further
      consideration to the use of sigmoids in contemporary population modelling and
      forecasting.  To do this a brief account is given of the historical development
      of these models, pointing out why demographers have viewed these trend models
      with scepticism.  Most of the paper is devoted to showing that, despite these
      criticisms, sigmoid-based trend models are useful practical tools for the
      demographer."  Examples using data for various countries are presented.

PMID- 12233647
TI  - [Effectiveness of socio-economic factors in determining levels and patterns of
      fertility: a demography study of Egypt (1950-1979)].

PMID- 12233648
TI  - [Population statistics].

PMID- 12233649
TI  - [Alternative approaches in extension and rural development work: an analysis of
      differing perspectives in Egypt].

PMID- 12233650
TI  - [The problem of illiteracy in Egypt].

PMID- 12233651
TI  - [Population trends and data of the elderly in the Arab Republic of Egypt].

PMID- 12233652
TI  - [The 1882 Census].

PMID- 12233653
TI  - [Workshop on Population and Development].

PMID- 12233654
TI  - [Population statistics].

PMID- 12233655
TI  - Mortality among infants of low birth weight in Israel, 1977-1980.

PMID- 12233656
TI  - Population projection in Israel up to 2010.

PMID- 12233657
TI  - Population in Israel, by marital status, sex and age, aged 15-54, 1987.

PMID- 12233658
TI  - Immigration to Israel, January-June 1991.
AB  - "This publication presents data on the immigration to Israel in the first half of
      1991.  In the period under review the number of immigrants to Israel amounted to
      110,600...compared to 57,600 immigrants in the first half of 1990 and about
      141,900 immigrants in the second half of 1990."  About 80 percent of immigrants
      were from the former Soviet Union, and 17 percent from Ethiopia.

PMID- 12233659
TI  - Projections of the population in Israel up to 2005.
AB  - "The Central Bureau of Statistics presents herewith new projections of the
      development of the population in Israel up to 2005.  The projections are for the
      years 1995, 2000 and 2005.  At the base of these projections is the estimated
      population at the end of 1990, by sex, age and population group...."

PMID- 12233660
TI  - Complete life tables of Israel, 1987-1991.
AB  - "This publication presents complete life tables [for Israel] for 1987-1991.  Data
      are detailed by single ages, for males and females separately.  The data are
      presented for the entire population and for Jews and Non-Jews separately."

PMID- 12233661
TI  - Immigration to Israel, January-June 1993.
AB  - "This publication presents data on the immigration to Israel in the first half of
      1993.  In the period under review the number of immigrants to Israel amounted to
      36,000--[seven] percent more than in the first half of 1992 (33,800)." 
      Information is included on country of origin.

PMID- 12233662
TI  - Indicators of the number of Israeli residents abroad, 1992.
AB  - "The aim of this publication is to provide up-to-date information on the number
      of Israeli residents who leave the country to live abroad for prolonged periods
      and to explain the meaning and limitations of these data."

PMID- 12233663
TI  - Projections of population in Israel up to 2003, based on the population in 1993.

PMID- 12233664
TI  - 1993 immigrants from former USSR by last republic of residence and by selected
      demographic characteristics.
AB  - "The purpose of this supplement is to present the demographic characteristics of
      the immigrants from the (former) Soviet Union, who arrived in Israel in 1993, by
      last republic of residence.... It attempts to answer the question whether there
      are demographic and social differences between immigrants from the various
      republics."

PMID- 12233665
TI  - Internal migration in Israel, 1993.

PMID- 12233666
TI  - 1994 immigrants from former USSR by last republic of residence and by selected
      demographic characteristics.

PMID- 12233667
TI  - Households of immigrants from USSR who arrived in Israel in October-December
      1990: a follow-up survey, three years after immigration.

PMID- 12233668
TI  - Births from pre-marital pregnancies among Jews, 1972-1990.
AB  - "This publication presents data on first births of Jewish married women [in
      Israel] who became pregnant prior to marriage." The data are for the period 1972
      1990.

PMID- 12233669
TI  - Socio-demographic characteristics of women applying for interruption of pregnancy
      in Israel, 1993.

PMID- 12233670
TI  - Demographic characteristics of women applying for interruption of pregnancy in
      Israel, 1992.

PMID- 12233671
TI  - Census of population and housing 1972: summary of final data from Stage B.

PMID- 12233672
TI  - Families in Israel, 1981.
AB  - This article "presents data on families (households) in Israel for the year 1981.
      The data are based on the series of civilian Labour Force Surveys conducted
      since 1954, and relate to the characteristics of families in Israel with regard
      to size of family, population group, age, continent of birth, years of schooling,
      type of locality of residence and sex of head of family."

PMID- 12233673
TI  - Immigrants who left Israel and did not return:  arrived 1969/70-1987.

PMID- 12233674
TI  - Immigration to Israel, I-IX 1990.

PMID- 12233675
TI  - Immigrants from USSR, 1990-1992:  demographic characteristics, by last republic
      of residence.
AB  - "The purpose of the publication is to present data, for each immigration year
      separately, on the difference or similarity between Soviet immigrants from
      different regions.  The publication seeks to answer the question of whether there
      are differences in the demographic and social composition of immigrants from the
      republics as follows:  Russia, Ukraine, Belarus, Moldova, the Baltic States and
      the Asian Republics." The period covered is 1990-1992.

PMID- 12233676
TI  - Cohabitation before marriage, 1990.
AB  - "In this publication, an attempt was made to gauge the extent to which
      cohabitation prior to marriage occurs, and to identify demographic
      characteristics which characterize this phenomenon. This study only relates to
      the Jewish population with the most updated figures relating to couples who
      married in Israel in 1990. Additionally, a comparison is made with previous
      years, starting in 1985."

PMID- 12233677
TI  - Complete life tables of Israel, 1989-1993.

PMID- 12233678
TI  - Internal migration in Israel, 1994.

PMID- 12233679
TI  - Infant mortality, 1975-1977.

PMID- 12233680
TI  - Population in Israel by marital status, age and sex, 1983-86.

PMID- 12233682
TI  - Demographic characteristics of women applying for interruption of pregnancy in
      Israel, 1991.

PMID- 12233681
TI  - Complete life tables of Israel, 1988-1992.
AB  - "This publication presents complete life tables for [Israel for] 1988-1992.  In
      the tables data are detailed by single ages, for males and females separately. 
      The data are presented for the entire population and for Jews and Non-Jews
      separately."

PMID- 12233683
TI  - Residents who departed in 1973 and did not return by the end of 1977.

PMID- 12233684
TI  - Families in Israel, 1978.

PMID- 12233685
TI  - [Summary of data on international migration and place of work: census of
      population and housing 1972, final data from Stage B].

PMID- 12233686
TI  - [Population in localities, 1972-1976].

PMID- 12233687
TI  - [Emigration from Israel, 1948-1977].

PMID- 12233688
TI  - [The reproductivity of Jewish marriage cohorts in Israel, 1966-1976].

PMID- 12233689
TI  - [Internal migration (between localities) of Jews in Israel, 1976, 1977].

PMID- 12233690
TI  - [Population in localities, December 31, 1978].

PMID- 12233691
TI  - [Characteristics of couples in Israel, average 1976-1978].

PMID- 12233692
TI  - [Estimates of total fertility].

PMID- 12233693
TI  - Families in Israel, 1979.
AB  - This publication "presents data on families (households) in Israel for the year
      1979. The data are based on the series of civilian Labour Force Surveys conducted
      since 1954, and relate to the characteristics of families in Israel with regard
      to size of family, population group, age, continent of birth, years of schooling,
      type of locality of residence and sex of family head."

PMID- 12233694
TI  - [Types of households, average 1977-1979].

PMID- 12233695
TI  - Immigrants who arrived in 1977/78 and 1978/79 one year after immigration
      (comparative data).
AB  - Comparative data are presented on immigrants who arrived in Israel between
      September 1977 and August 1978 and those who arrived between September 1978 and
      August 1979.  The data are derived from the Survey of Absorption of Immigrants,
      which is considered "to follow-up the immigrants during the first year of their
      stay in Israel, from the point of view of absorption at work and in housing,
      social life, command of the Hebrew language and their position in these fields,
      and their feelings and attitudes as to their present situation and their future
      in Israel."

PMID- 12233696
TI  - [Immigration to Israel, 1980].

PMID- 12233697
TI  - Families in Israel, 1980.
AB  - This publication "presents data on families (households) in Israel for the year
      1980.  The data are based on the series of civilian Labour Force Surveys
      conducted since 1954, and relate to the characteristics of families in Israel
      with regard to size of family, population group, age, continent of birth, years
      of schooling, type of locality of residence and sex of family head."

PMID- 12233698
TI  - [Immigrants who left Israel within 1-5 years since immigration (arrived 1969
      1980)].

PMID- 12233699
TI  - [Sources of population increase in localities of 50,000 and more residents, June
      30, 1977; December 31, 1980].

PMID- 12233700
TI  - [Characteristics of couples in Israel, average 1978-1980].

PMID- 12233701
TI  - Immigrants who arrived in 1977/78, 1978/79 and 1979/80 one year after immigration
      (comparative data).

PMID- 12233702
TI  - Population and vital statistics, 1981.
AB  - "For various reasons some of the data relating to population estimates, vital
      statistics and causes of death in 1981 were not included in the Statistical
      Abstract of Israel No. 33, 1982.  The purpose of this [article] is to complete
      the missing data and to revise and update some other data."  Statistics are
      included on population by age, sex, marital status, population group, origin,
      continent of birth, period of immigration, and religion; marriages, divorces,
      live births, deaths, natural increase, infant deaths, and stillbirths by
      religion; characteristics of persons marrying and divorcing, including place of
      residence, religion, age, previous marital status, and year and duration of
      marriage; live births, deaths, and infant deaths by district, sub-district, and
      type of locality of residence; deaths by age, sex, and continent of birth; infant
      deaths by age, sex, and population group; and selected life table values by
      population group and sex.

PMID- 12233703
TI  - Census of population and housing, 1983.  Population and households in Jerusalem,
      Tel Aviv and Haifa, by statistical area, sub-quarter and quarter.  Selected
      demographic characteristics from the complete enumeration.

PMID- 12233706
TI  - [Some complementary observations on Portuguese emigration policy].

PMID- 12233707
TI  - [Migration, social mobility, and cultural identity:  facts and hypotheses about
      the Portuguese case].

PMID- 12233709
TI  - Types of female genital mutilation.

PMID- 12233711
TI  - Regional cerebral blood flow changes in drug-resistant depressed patients
      following treatment with transcranial magnetic stimulation: a statistical
      parametric mapping analysis.

PMID- 12233710
TI  - Nitric oxide as a mediator of glaucoma pathogenesis.

PMID- 12233712
TI  - [Efficient selection mechanisms: requirement for successful gene therapy. 5th
      Congress of the American Society of Gene Therapy].

PMID- 12233713
TI  - [Straying endoparasites--swimmer's dermatitis].

PMID- 12233714
TI  - Urinary excretion of pneumococcal cell wall polysaccharide in children.
AB  - The urinary excretion of the cell wall polysaccharide of Streptococcus pneumoniae
      was studied in 92 children with the NOW test. Cell wall polysaccharide was
      detected in 65% of pneumococcal carriers and in 10% of noncarriers. Excretion
      rates were similar in healthy children and in children with acute otitis media.
      The high rate of antigen excretion among nonill carriers suggests that
      colonization is a major source of urinary antigen in children.

PMID- 12233715
TI  - Persistence of antibody and immunologic memory in children immunized with
      hepatitis B vaccine at birth.
AB  - Forty-two healthy children immunized with a course of hepatitis B vaccine
      beginning at birth were tested at 6 years of age for persistence of anti
      hepatitis B antibody (anti-HBs) and then given a booster dose of vaccine.
      Although nearly one-half had become seronegative, all retained robust immunologic
      memory and rapidly regained a protective anti-HBs titer of at least 10 mIU/ml
      after booster vaccination.

PMID- 12233716
TI  - Dual infection with influenza A and B viruses.
AB  - A throat swab from a 7-year-old child with a mild influenza-like illness was
      cultured for respiratory viruses by standard and rapid plate culture methods.
      Standard culture yielded influenza B, whereas influenza A was obtained from rapid
      plate culture. Testing of the original sample by PCR confirmed the presence of
      both viruses. A surveillance program (Viral Watch) for respiratory viruses showed
      cocirculation of both these viruses in the community during this period.

PMID- 12233717
TI  - Placental transfer of ganciclovir in a woman with acquired immunodeficiency
      syndrome and cytomegalovirus disease.
AB  - A pregnant woman with AIDS developed cytomegalovirus (CMV) retinitis and
      pneumonitis, requiring intravenous ganciclovir. At 34 weeks gestation the woman
      delivered a 1.4-kg girl. Examination of the placenta revealed transplacental
      passage of CMV. Low concentrations of ganciclovir were detected in the neonate's
      plasma. The neonate had mild anemia but no other signs of congenital CMV
      infection.

PMID- 12233718
TI  - Spinal epidural abscess in a neonate.
AB  - A case of purulent spinal epidural abscess in a 20-day-old girl is presented. The
      patient had symptoms of fever, localized back pain and swelling over the
      interscapular area. The diagnosis was made by magnetic resonance imaging.
      Purulent material grew Staphylococcus aureus from the lesion. Because of severe
      cord compression surgical laminotomy and drainage were performed, and antibiotics
      were administered. One year later she was doing well without neurologic sequelae.

PMID- 12233720
TI  - Bibliography. Current world literature. Systemic lupus erythematosus and
      Sjogren's syndrome.

PMID- 12233719
TI  - Linezolid treatment of vancomycin-resistant Enterococcus faecium ventriculitis.
AB  - The successful treatment of a 7-month-old infant with shunt-associated
      ventriculitis caused by vancomycin-resistant Enterococcus faecium is presented.
      Linezolid was administered intravenously every 8 h; children have a greater
      volume of distribution and total body clearance than adults and therefore require
      more frequent dosing. The patient tolerated the therapy without adverse effects.

PMID- 12233721
TI  - Does your blood need a boost?

PMID- 12233722
TI  - Restoring peace--and health--to troubled snorers.

PMID- 12233723
TI  - Keeping your kidneys out of trouble.

PMID- 12233724
TI  - The latest crinkle in banishing wrinkles.

PMID- 12233725
TI  - Should people with diverticulosis avoid certain foods?

PMID- 12233726
TI  - The West Nile Virus epidemic.

PMID- 12233727
TI  - Which mosquito repellents work best?

PMID- 12233728
TI  - Beware the kiss of the peanut eater.

PMID- 12233729
TI  - Warning about placing babies in adult beds.

PMID- 12233730
TI  - Is modeling clay a hazard to children?

PMID- 12233731
TI  - Resource: assuring the safety of art and craft materials.

PMID- 12233732
TI  - Product recalls. BRIO snail pull toy...and Pottery Barn Kids wooden clacker and
      ride-on toys.

PMID- 12233733
TI  - The price of anticancer intervention. A paediatric perspective.

PMID- 12233734
TI  - The price of anticancer intervention. Secondary malignancies after radiotherapy.

PMID- 12233735
TI  - The price of anticancer intervention. Does surgery promote metastasis?

PMID- 12233736
TI  - Optimization of single-step purification of alkaline protease using different
      hydrophobic ligands.
AB  - The adsorption and desorption pattern of alkaline protease was studied using
      different aliphatic and aromatic hydrophobic ligands. Overall, higher adsorption
      was obtained on ligands coupled to 6% cross-linked gel than the 4% gel. The
      highest adsorption was obtained on butyl (94%) and phenyl (98.4%) of 6% cross
      linked gel. The adsorption was dependent on concentration and nature of the
      ligand. In a single-step operation, almost 20-fold purification with 40% yield of
      the enzyme was obtained using all the optimized experimental parameters.

PMID- 12233737
TI  - Study on the scale-up of human IgG3 purification using protein A affinity
      chromatography.
AB  - The purification of human IgG3 subclass out of IgG (Immunoglobulin-G) was studied
      using protein A-Sepharose affinity chromatography. The effect of operational
      parameters such as flow rate, ionic strength, pH and size of sample was
      investigated, and the process was scaled-up 10-fold. The use of 0.5 m NaCl in the
      loading buffer had a dramatic effect in the purity of IgG3 recovered in the
      flowthrough fraction (values in the order of 97% were consistently obtained).
      This was attributed to a more effective binding of IgG subclasses 1, 2 and 4 to
      protein A (well known classical mechanism based in Fc fragment) and in some
      extent to a decrease in the binding of subclass 3 to protein A by the alternative
      mechanism based in the Fab fragment. The increase in residence time also
      increased in a relevant way the purity of IgG3. This is attributed to an
      increased effectiveness of the mechanisms mentioned above. The recovery yields in
      the IgG3 rich fraction were in the range 21-32% and are possibly a consequence of
      binding to protein A by the alternative mechanism and also due to deactivation
      during processing.

PMID- 12233738
TI  - Electrophoretic methods for fractionation of native and heat-denatured bovine
      beta-lactoglobulin.
AB  - We have developed three electrophoretic methods for analytical and preparative
      separation of native and heat-denatured beta-lactoglobulin. The methods can be
      applied, e.g., to optimize dairy milk processing, especially in laboratories
      which are not provided with expensive column chromatographic instruments. The
      methods consist of native PAGE followed by electroelution. Consequently, the
      eluted proteins are in solution in a biologically active and native form, and can
      therefore be used immediately for further analyses.

PMID- 12233739
TI  - A study of the spatial organisation of microbial cells in a gel matrix subjected
      to treatment with ultrasound standing waves.
AB  - Retention and manipulation of microbial cells through exploitation of ultrasonic
      forces has been reported as a novel cell immobilisation technique. The spatial
      ordering of yeast cells, within suspensions subjected to an ultrasonic standing
      wave field, was analysed for the first time. A technique, based on 'freezing' the
      spatial arrangement using polymer gelation was developed. The resultant gel was
      then sectioned and examined using microscopic techniques. Light Microscopy
      confirmed the presence of specific regions in the ultrasonic field, where the
      cells are organised into bands corresponding to the standing waves' pressure
      nodal planes. Computer Image Analysis measurement of several physical parameters
      associated with this cell distribution matched the values derived from the
      theoretical model. The spatial cell-cell re-arrangement within each band and
      uneven distribution along the nodal planes have been analysed by Scanning
      Electron Microscopy. These results complement the ongoing study of the process of
      immobilisation of microbial cells by ultrasound standing waves.

PMID- 12233740
TI  - The potential of polymeric cryogels in bioseparation.
AB  - This is a review discussing the production and properties of cryogels (from the
      Greek kappa rho iota sigma (kryos) meaning frost or ice), immobilization of
      ligands in cryogels and the application of affinity cryogels in bioseparation.
      Cryotropic gel formation proceeds in a non-frozen liquid microphase existing in
      the macroscopically frozen sample. Due to the cryoconcentration of gel precursors
      in the non-frozen liquid microphase, cryogelation is characterised by a decrease
      in the critical concentration of gelation and an increase in gelation rates
      compared with traditional gelation at temperatures above freezing point. Cryogels
      can be obtained through the formation of both physically and covalently cross
      linked heterogeneous polymer networks. Interconnected systems of macropores and
      sponge-like morphology are typical for cryogels, allowing unhindered diffusion of
      solutes of practically any size. Most of the water present in spongy cryogels is
      capillary bound and can be removed mechanically by squeezing. The properties of
      cryogels can be regulated by the temperature of cryogelation, the time the sample
      is kept in a frozen state and freezing/thawing rates, by the nature of the
      solvent and by the use of soluble and insoluble additives. The unique macroporous
      morphology of cryogels, in combination with osmotic, chemical and mechanical
      stability, makes them attractive matrices for chromatography of large entities
      such as protein aggregates, membrane fragments, viruses, cell organells and even
      whole cells. Special attention is given to immunosorption of viruses on cryogel
      based sorbents. As chromatographic materials, cryogels can be used both in bead
      form and as spongy cylindrical blocks (monoliths) synthesized inside the
      chromatographic column. The macroporous nature of cryogels is also advantageous
      for their application as matrices in the immobilization of biocatalysts operating
      in both aqueous and organic solvents. New potential applications of cryogels are
      discussed.

PMID- 12233741
TI  - Refolding of protein inclusion bodies directly from E. coli homogenate using
      expanded bed adsorption chromatography.
AB  - To avoid the intrinsic problem of aggregation associated with the traditional
      solution-phase refolding process, we proposed a solid-phase refolding method
      integrated with the expanded bed adsorption chromatography. The model protein was
      a fusion protein of recombinant human growth hormone and a glutathione S
      transferase fragment. It was demonstrated that the inclusion body proteins in the
      cell homogenate could be directly refolded with higher yield. To verify the
      applicability of this method, we have tested with success three types of the
      starting materials, i.e., rhGH monomer, inclusion bodies containing the fusion
      protein, and the E. coli cell homogenate. This direct refolding process could
      reduce the number of the renaturation steps required and allow the refolding at a
      higher concentration, approximately 2 mg fusion protein per ml resin.

PMID- 12233742
TI  - Scaled down method for the reproducible recovery to high purity of human serum
      albumin from low volume blood samples.
AB  - A basic need for a protein-based dosimeter is a purified protein. In this
      communication we present an isolation protocol and an HPLC-based assay which
      allows one to determine the purity of the isolated albumin. A total of 168 human
      blood samples were collected from workers of a benzene processing plant and from
      nearby countryside at Kohtla-Jarve, Estonia. Albumin was isolated from plasma by
      sequential precipitation and the purity was determined by HPLC. The amount of
      albumin present in plasma varied between the individuals, being 147 +/- 26 mg/5
      ml (n = 168), which is about 59% of plasma albumin. However, the isolated albumin
      was highly pure (100.9 +/- 8.2%, n = 5). All albumin samples analyzed demonstrate
      two peaks in HPLC analysis. The two peaks detected were collected and subjected
      to MS analysis, which demonstrates a difference of 120 mass units between the two
      albumin products isolated. We have developed an assay, which is easy to carry out
      and is not too labor intense. The HPLC analysis can be applied to confirm the
      purity of the isolated albumin as well as to confirm the quantity of the albumin
      in samples.

PMID- 12233743
TI  - Acoustic field assisted demixing of aqueous two-phase polymer systems.
AB  - Acoustic field assisted demixing was employed to decrease the demixing time in
      polymer-polymer (polyethylene glycol-maltodextrin) two-phase system. Application
      of acoustic field has decreased the demixing time in these systems up to 2-fold.
      Ultrasonication has induced mild circulation currents in the phase dispersion,
      which has enhanced the rate of droplet coalescence, eventually resulting in
      decreased demixing time. In polymer-polymer systems, phase demixing was found to
      depend greatly on which of the phases is continuous and viscosity of the
      continuous phase was observed to have a strong influence on the movement of the
      droplets and hence the phase demixing. Addition of NaCl increased the demixing
      time and presence of E. coli cells did not seem to have any influence on phase
      demixing.

PMID- 12233744
TI  - Studies on the retention of plasmid DNA and Escherichia coli nucleic acids by
      hydrophobic interaction chromatography.
AB  - This work presents studies on the interactions of supercoiled plasmid DNA and
      Escherichia coli genomic DNA (gDNA) and RNA, with an hydrophobic interaction
      chromatography (HIC) gel, obtained by derivatisation of Sepharose CL-6B with 1,4
      butanediol diglycidyl ether. Nucleic acids purified from E. coli were injected
      separately in the above HIC column and eluted with 1.5 M (NH4)2SO4 in the buffer.
      The column was able to separate single-stranded from double-stranded nucleic
      acids. RNA and denatured gDNA were retarded in a different way due to the
      interactions of the exposed hydrophobic bases with the ligands. Supercoiled
      plasmid DNA, on the contrary, eluted in the flowthrough.

PMID- 12233745
TI  - Kinetic studies of clavulanic acid recovery by ion exchange chromatography.
AB  - Clavulanic acid (CA) is a beta-lactamase inhibitor produced by strains of
      Streptomyces clavuligerus. Nowadays, the combination of CA with amoxycillin is
      the most successful example of the use of a beta-lactam antibiotic sensitive to
      beta-lactamases together with an inhibitor of these enzymes. Clavulanic acid is
      purified from fermentation broth by a series of steps consisting mainly of two
      phase separation processes such as liquid-liquid extraction, adsorption or ion
      exchange chromatography, among others. Amberlite IRA 400, a strong anion-exchange
      resin, has a very high adsorption capacity for CA (Mayer et al. 1997). This resin
      can be pre-treated with NaCl (chloride cycle), to remove selectively only those
      anions, which are able to displace chloride from the resin or with NaOH (hydroxyl
      cycle), to remove all species of anions. In order to decide the best operating
      conditions for CA recovery by ion-exchange resins and then to construct a model
      of this separation process, batch experiments were conducted using Amberlite IRA
      400 in the chloride cycle. These runs were carried out in a 200 ml stirred tank,
      at two different initial solution pH, 6.2 and 4.0; the temperature was maintained
      at 10 degrees C and 20 degrees C during adsorption and 30 degrees C during the
      desorption step. It was possible, on the basis of these batch results, to model
      the separation process, including the adsorption kinetics, equilibrium data and
      mass transfer limitations.

PMID- 12233746
TI  - Parameters influencing protein extraction for whole broths in detergent based
      aqueous two-phase systems.
AB  - The parameters important for an optimisation of cloud point extraction in
      technical scale were investigated using a genetically engineered fusion protein
      derived from endoglucanase I expressed in Trichoderma reesei and the nonionic
      polyoxyethylene Agrimul NRE 1205. The key parameters are temperature, detergent
      concentration, and additional salts. These parameters are interdependent, thus
      there is an optimum in the partition coefficient with respect to detergent
      concentration and a maximum for the partition coefficient and the yield with
      respect to temperature. These results were confirmed for the detergent C12E5 to
      demonstrate that these optima are due to the nature of polyoxyethylenes. Cloud
      point extraction was found to be only slightly affected by pH. In the case
      studied extraction of whole broth is favourable for a high yield and partition
      coefficient, since fusion protein adhering to the cells can be solubilized.
      However some loss of detergent which remains in the fungal biomass was observed.

PMID- 12233747
TI  - Isolation, purification and preliminary characterization of cryophilic proteases
      of marine origin.
AB  - The isolation and preliminary characterization of a trypsin-like protease with
      high activity at 20 degrees C is described. This protease was isolated from
      Antarctic krill (Euphasia superba) by a two-step chromatography process and the
      use of zymogram analyses. The protease has a molecular weight of 30 kDa and a pI
      of 4.1. Its specific activity at 20 degrees C on BAPNA is 0.5 U/mg.

PMID- 12233748
TI  - Physical properties of detergent-based aqueous two-phase systems.
AB  - The physical behavior of the binary phase systems of the non-ionic
      polyoxyethylene detergent Agrimul NRE 1205 and water was investigated. This
      technical detergent can be used for the large-scale recovery of biomolecules in
      detergent based aqueous two-phase systems. The phase diagram was determined. It
      shows significant and unexpected differences to highly purified detergents. Very
      similar to neat detergents the phase diagram can be influenced by auxiliary
      chemicals thus shifting the entire phase diagram in general to lower
      temperatures. This was demonstrated by lowering the cloud-point by various
      additions. The concentration factor, as an important parameter of a first capture
      step in purification was investigated and modeled. Auxiliary chemicals,
      temperature change and change in detergent concentration also influence the
      viscosity and density of the phases. These experimental data are shown. They can
      help to explain the separation behavior of proteins. In large-scale separations
      aqueous two-phase systems are separated using disc-stack centrifuges. It is
      demonstrated that this is not a feasible method for detergent-based aqueous two
      phase extraction and the physical reason is presented.

PMID- 12233750
TI  - UK report recommends further research on water fluoridation and health.

PMID- 12233751
TI  - Professor warns of "brain drain" of diabetes researchers from Europe.

PMID- 12233752
TI  - India considers government agency to license infertility clinics.

PMID- 12233753
TI  - Australia proposes peer review of alleged negligence cases.

PMID- 12233754
TI  - New abortion guidelines proposed for Ireland.

PMID- 12233755
TI  - Aspects of MMR. Trying to find biological cause for autism does not make sense.

PMID- 12233756
TI  - Brain death. Fear has basis in reason.

PMID- 12233757
TI  - The advanced life support provider course.

PMID- 12233758
TI  - Can superstitious behaviour reduce work stress?

PMID- 12233763
TI  - Medicare program; Medicare-Endorsed Prescription Drug Card Assistance Initiative.
      Final rule.
AB  - This final rule describes the Department of Health and Human Services' (HHS)
      Medicare-Endorsed Prescription Drug Card Assistance Initiative, and sets forth
      the necessary requirements to participate in the initiative.

PMID- 12233764
TI  - Mental health and substance abuse emergency response criteria. Final rule.
AB  - Section 3102 of the Children's Health Act of 2000, Pub. L. 106-310, amends
      section 501 of the Public Health Service (PHS) Act (42 U.S.C. 290aa) to add a new
      subsection (m) entitled "Emergency Response." This newly enacted subsection
      501(m) authorizes the Secretary to use up to, but no more than, 2.5% of all
      amounts appropriated under Title V of the PHS Act, other than those appropriated
      under Part C, in each fiscal year to make "noncompetitive grants, contracts or
      cooperative agreements to public entities to enable such entities to address
      emergency substance abuse or mental health needs in local communities." Because
      Congress believed the Secretary needed the ability to respond to emergencies, it
      exempted any grants, contracts, or cooperative agreements authorized under this
      section from the peer review process. See section 501(m)(1) of the PHS Act.
      Instead, the Secretary is to use an objective review process by establishing
      objective criteria to review applications for funds under this authority.

PMID- 12233765
TI  - A functional angle on some after-effects in cortical vision.
AB  - The question of how our brains and those of other animals code sensory
      information is of fundamental importance to neuroscience research. Visual
      illusions offer valuable insight into the mechanisms of perceptual coding. One
      such illusion, the tilt after-effect (TAE), has been studied extensively since
      the 1930s, yet a full explanation of the effect has remained elusive. Here, we
      put forward an explanation of the TAE in terms of a functional role for
      adaptation in the visual cortex. The proposed model accounts not only for the
      phenomenology of the TAE, but also for spatial interactions in perceived tilt and
      the effects of adaptation on the perception of direction of motion and colour. We
      discuss the implications of the model for understanding the effects of adaptation
      and surround stimulation on the response properties of cortical neurons.

PMID- 12233766
TI  - Listening for bats: the hearing range of the bushcricket Phaneroptera falcata for
      bat echolocation calls measured in the field.
AB  - The hearing range of the tettigoniid Phaneropterafalcata for the echolocation
      calls of freely flying mouseeared bats (Myotis myotis) was determined in the
      field. The hearing of the insect was monitored using hook electrode recordings
      from an auditory interneuron, which is as sensitive as the hearing organ for
      frequencies above 16 kHz. The flight path of the bat relative to the insect's
      position was tracked by recording the echolocation calls with two microphone
      arrays, and calculating the bat's position from the arrival time differences of
      the calls at each microphone. The hearing distances ranged from 13 to 30 m. The
      large variability appeared both between different insects and between different
      bat approaches to an individual insect. The escape time of the bushcricket,
      calculated from the detection distance of the insect and the instantaneous flight
      speed of the bat, ranged from 1.5 to more than 4s. The hearing ranges of
      bushcrickets suggest that the insect hears the approaching bat long before the
      bat can detect an echo from the flying insect.

PMID- 12233767
TI  - Pursuit plunging by northern gannets (Sula bassana) feeding on capelin (Mallotus
      villosus).
AB  - Northern gannets (Sula bassana) are considered to obtain prey usually by rapid,
      vertical, shallow plunge dives. In order to test this contention and investigate
      underwater foraging behaviour, we attached two types of data-logging systems to
      11 parental northern gannets at Funk Island in the North-Wiest Atlantic. We
      documented, for the first time to the authors' knowledge, gannets performing
      long, flat-bottomed, U-shaped dives that involved underwater wing propulsion as
      well as rapid, shallow, V-shaped dives. The median and maximum dive depths and
      durations were 4.6 and 22.0 m and 8 and 38 s, respectively. Short, shallow dives
      were usually V-shaped and dives deeper than 8 m and longer than 10 s were usually
      U-shaped, including a period at constant depth (varying between 4 and 28s with
      median 8s). Diving occurred throughout the daylight period and deepest dives were
      performed during late morning. On the basis of motion sensors in the loggers and
      food collections from telemetered birds, we concluded that extended, deep dives
      were directed at deep schools of capelin, a small pelagic fish, and we
      hypothesized that V-shaped dives were aimed at larger, pelagic fishes and squids.
      Furthermore, these V-shaped dives allowed the birds to surprise their pelagic
      prey and this may be critical because the maximum swimming speeds of the prey
      species may exceed the maximum dive speeds of the birds.

PMID- 12233768
TI  - Experimental evidence for offspring learning in parent-offspring communication.
AB  - The offspring of birds and mammals solicit food from their parents by a
      combination of movements and vocalizations that have come to be known
      collectively as 'begging'. Recently, begging has most often been viewed as an
      honest signal of offspring need. Yet, if offspring learn to adjust their begging
      efforts to the level that rewards them most, begging intensities may also reflect
      offsprings' past experience rather than their precise current needs. Here we show
      that bird nestlings with equal levels of need can learn to beg at remarkably
      different levels. These experiments with hand-raised house sparrows (Passer
      domesticus) indicated that chicks learn to modify begging levels within a few
      hours. Moreover, we found that the begging postures of hungry chicks in natural
      nests are correlated with the average postures that had previously yielded them
      parental feedings. Such learning challenges parental ability to assess offspring
      needs and may require that, in response, parents somehow filter out learned
      differences in offspring signals.

PMID- 12233769
TI  - Rank orders and division of labour among unrelated cofounding ant queens.
AB  - Young, unrelated queens may cooperate in colony founding (pleometrosis) in many
      species of ants. Whereas the founding queens of many 'advanced' species rely
      completely on body reserves in order to rear their first young, queens of the
      ponerine Pachycondyla 'inversa' forage for food. In founding associations, only
      one queen specializes in this risky task. Here we show that the division of
      labour is strongly affected by aggressive interactions between cofounding queens:
      the dominant remains in the nest and guards the brood, whereas the subordinate is
      forced to leave and forage. The frequency of queen antagonism increased with the
      duration since food was last added to the foraging arena. Egg-laying rates did
      not differ significantly between nest-mate queens, but dominant queens destroyed
      and ate some of the eggs laid by subordinates.

PMID- 12233770
TI  - Co-option of male courtship signals from aggressive display in bowerbirds.
AB  - The pre-existing trait hypothesis suggests that females evolve a mating
      preference for an already existing male trait. This hypothesis poses a simple
      resolution to Darwin's long-standing question of how elaborate, male display
      traits evolve. The frequently observed convergence of aggressive and courtship
      displays across a wide array of species provides the only current support for
      this hypothesis. Here we provide much more detailed supporting evidence from
      bowerbird skrraa calls used in aggression and courtship. Consistent with the pre
      existing trait hypothesis we show that (i) putatively co-opted skrraa calls used
      in courtship and aggression are homologous, (ii) skrraa calls were used in
      aggression in bowerbirds before being used in courtship, (iii) historically,
      intense, aggressive-like courtship calls were present near the time of co-option,
      and (iv) bower types contemporaneous with co-option emphasize design features
      that provide females protection from the adverse effects of intense courtship
      displays. These results, plus evidence for a female preference for males with
      intense aggressive-like courtship skrraa calls, suggest that aggressive skrraa
      calls have been co-opted for use in male courtship display

PMID- 12233771
TI  - Fragile transmission cycles of tick-borne encephalitis virus may be disrupted by
      predicted climate change.
AB  - Repeated predictions that vector-borne disease prevalence will increase with
      global warming are usually based on univariate models. To accommodate the full
      range of constraints, the present-day distribution of tick-borne encephalitis
      virus (TBEv) was matched statistically to current climatic variables, to provide
      a multivariate description of present-day areas of disease risk. This was then
      applied to outputs of a general circulation model that predicts how climatic
      variables may change in the future, and future distributions of TBEv were
      predicted for them. The expected summer rise in temperature and decrease in
      moisture appears to drive the distribution of TBEv into higher-latitude and
      higher-altitude regions progressively through the 2020s, 2050s and 2080s. The
      final toe-hold in the 2080s may be confined to a small part of Scandinavia,
      including new foci in southern Finland. The reason for this apparent contraction
      of the range of TBEv is that its transmission cycles depend on a particular
      pattern of tick seasonal dynamics, which may be disrupted by climate change. The
      observed marked increase in incidence of tick-borne encephalitis in most parts of
      Europe since 1993 may be due to non-biological causes, such as political and
      sociological changes.

PMID- 12233772
TI  - Environmental sex determination in a reptile varies seasonally and with yolk
      hormones.
AB  - Most hypotheses that have been put forward in order to explain the persistence of
      environmental sex determination (ESD) in reptiles assume a relatively fixed
      association of sex with temperature-induced phenotype and no maternal influence
      on offspring sex. Here we demonstrate the association of maternally derived yolk
      hormone levels with the offspring sex ratio and describe two new aspects of
      temperature-dependent sex determination (TSD), i.e. seasonal variation in both
      thermal response and yolk steroid levels. Eggs from painted turtles (Chrysemys
      picta) were incubated at 28 degrees C. The hatchling sex ratio at 28 degrees C
      (i.e. the phenotypic reaction norm for sex at 28 degrees C) shifted seasonally
      from ca. 72% male to ca. 76% female. Yolk oestradiol (E2) increased seasonally
      while testosterone (T) decreased. The proportion of males in a clutch decreased
      as E2 levels increased and the E2:T ratio increased. These new findings are
      discussed in relation to heritability and adaptive explanations for the
      persistence of ESD in reptiles. Maternally derived yolk hormones may provide a
      mechanism for the seasonal shift in the sex ratio which in turn may help explain
      the persistence of ESD in reptiles. They may also explain those clutches of other
      reptiles with TSD that fail to yield only males at maximally masculinizing
      conditions.

PMID- 12233773
TI  - Colony sex ratios vary with queen number but not relatedness asymmetry in the ant
      Formica exsecta.
AB  - Split-sex-ratio theory assumes that conflict over whether to produce
      predominately males or female reproductives (gynes) is won by the workers in
      haplodiploid insect societies and the outcome is determined by colony kin
      structure. Tests of the theory have the potential to provide support for kin
      selection theory and evidence of social conflict. We use natural variation in
      kinship among polygynous (multiple-queen) colonies of the ant Formica exsecta to
      study the associations between sex ratios and the relatedness of workers to
      female versus male brood (relatedness asymmetry). The population showed split sex
      ratios with about 89% of the colonies producing only males, resulting in an
      extremely male-biased investment ratio in the population. We make two important
      points with our data. First, we show that queen number may affect sex ratio
      independently of relatedness asymmetry. Colonies producing only males had greater
      genetic effective queen number but did not have greater relatedness asymmetry
      from the perspective of the adult workers that rear the brood. This lack of a
      difference in relatedness asymmetry between colonies producing females and those
      producing only males was associated with a generally low relatedness between
      workers and brood. Second, studies that suggest support for the relatedness
      asymmetry hypothesis based on indirect measures of relatedness asymmetry (e.g.
      queen number estimated from relatedness data taken from the brood only) should be
      considered with caution. We propose a new hypothesis that explains split sex
      ratios in polygynous social insects based on the value of producing replacement
      queens.

PMID- 12233774
TI  - Spermicide by females: what should males do?
AB  - The female reproductive tract can be particularly aggressive towards ejaculates,
      often leading to the death of large numbers of sperm. It has been suggested that
      males can respond to these actions by investing more in sperm and donating larger
      ejaculates. Such counteractions may lead to arms races, which can have
      significant implications for the mating system. In a series of simple models we
      first show that arms races are not necessarily supported: in fact, sperm killing
      may even favour no change or reductions in sperm allocation. Second, we identify
      a simple mechanistic rule for sperm killing that determines whether an arms race
      or sperm reduction will be favoured. Which of these responses is favoured by
      selection depends on whether a certain number, or proportion, of sperm are
      killed. When a specific number is killed, larger investment in sperm is favoured
      and when a specific proportion is killed, no change or lower investment in sperm
      is favoured. Both of these mechanisms are biologically plausible.

PMID- 12233775
TI  - Fitness, reproduction and longevity among European aristocratic and rural Finnish
      families in the 1700s and 1800s.
AB  - The life histories of two socio-economically different groups of humans
      comprising birth cohorts from the 1700s and 1800s were investigated. It was
      discovered that fertility selection was greater among European aristocrats and
      mortality selection greater among rural Finns. The life history of the rural
      Finns involved shorter female life spans, a considerably longer period of
      reproduction, higher juvenile mortality, a greater total production of offspring
      and slightly higher individual fitness. In a comparison of parental cohorts, it
      was discovered that longevity and progeny survival improved significantly from
      the 1700s to the 1800s. Out of the three factors investigated, longevity was
      found to influence reproduction and fitness more than socio-economic group or
      birth cohort. The reproductive efficacy and fitness of women increased along with
      their life span. However, reproductive success and fitness were lower among women
      with the longest life span (over 80 years). Among men, reproductive success
      improved consistently along with the increase in longevity. When birth intervals
      were examined, it was discovered that the sex of previous offspring did not
      influence the interval between births.

PMID- 12233776
TI  - The relative roles of density and climatic variation on population dynamics and
      fecundity rates in three contrasting ungulate species.
AB  - The relative influences of density-dependent and -independent processes on vital
      rates and population dynamics have been debated in ecology for over half a
      century, yet it is only recently that both processes have been shown to operate
      within the same population. However, generalizations on the role of each process
      across species are rare. Using a process-orientated generalized linear modelling
      approach we show that variations in fecundity rates in populations of three
      species of ungulates with contrasting life histories are associated with density
      and winter weather in a remarkably similar manner. However, there are differences
      and we speculate that they are a result of differences in size between the
      species. Much previous research exploring the association between vital rates,
      population dynamics and density-dependent and -independent processes has used
      pattern-orientated approaches to decompose time-series into contributions from
      density-dependent and -independent processes. Results from these analyses are
      sometimes used to infer associations between vital rates, density and climatic
      variables. We compare results from pattern-orientated analyses of time-series
      with process-orientated analyses and report that the two approaches give
      different results. The approach of analysing relationships between vital rates,
      density and climatic variables may detect important processes influencing
      population dynamics that time-series methodologies may overlook.

PMID- 12233777
TI  - The importance of transients' dynamics in spatially extended populations.
AB  - Recent theoretical works on the dynamics of metapopulations have highlighted the
      existence of very long transients (supertransients) with abrupt changes in
      behaviour which occur following perturbation of the system away from its
      attractor. If this phenomenon is common in natural systems, populations that do
      not oscillate can begin to fluctuate wildly without any change in the
      environmental conditions. However, the frequency of occurrence of supertransients
      is currently poorly understood even in model systems. Here we explore their
      occurrence in metapopulation models which relax the important assumption of
      global synchrony of events implicit in all the coupled map lattice models for
      which supertransients have so far been demonstrated. We find supertransients in
      all the models but always only for a very restricted range of parameter
      combinations. However, we also report for the first time another type of longer
      lived transient (mesotransients) that occurs on shorter time-scales than
      supertransients and is found for a much wider set of conditions. We argue that
      these medium-term changes in the dynamics of populations can be of more
      ecological relevance than the long-term changes of supertransients.

PMID- 12233778
TI  - Canonical functions for dispersal-induced synchrony.
AB  - Two processes are universally recognized for inducing spatial synchrony in
      abundance: dispersal and correlated environmental stochasticity. In the present
      study we seek the expected relationship between synchrony and distance in
      populations that are synchronized by density-independent dispersal. In the
      absence of dispersal, synchrony among populations with simple dynamics has been
      shown to echo the correlation in the environment. We ask what functional form we
      may expect between synchrony and distance when dispersal is the synchronizing
      agent. We formulate a continuous-space, continuous-time model that explicitly
      represents the time evolution of the spatial covariance as a function of spatial
      distance. Solving this model gives us two simple canonical functions for
      dispersal-induced covariance in spatially extended populations. If dispersal is
      rare relative to birth and death, then covariances between nearby points will
      follow the dispersal distance distribution. At long distances, however, the
      covariance tails off according to exponential or Bessel functions (depending on
      whether the population moves in one or two dimensions). If dispersal is common,
      then the covariances will follow the mixture distribution that is approximately
      Gaussian around the origin and with an exponential or Bessel tail. The latter
      mixture results regardless of the original dispersal distance distribution. There
      are hence two canonical functions for dispersal-induced synchrony

PMID- 12233779
TI  - Mesoscale vortices and the paradox of the plankton.
AB  - Coexistence of competitive species is severely limited by the availability of
      resources and the characteristics of the environment. In particular, the so
      called 'competitive exclusion principle' states that, at equilibrium, the number
      of coexisting species cannot be larger than the number of resources for which
      they compete. However, many in situ observations have revealed prolonged
      coexistence of a large number of competitive plankton species, a phenomenon known
      as 'the paradox of the plankton'. Here we investigate this problem and show that
      ocean mesoscale vortices generate transport barriers and incomplete horizontal
      mixing, allowing for a prolonged survival of the less-fit species, even for fully
      homogeneous resource distributions. In such a situation, the temporarily less-fit
      plankton species are protected from competition by the action of the vortices.

PMID- 12233780
TI  - Linkage disequilibrium and phylogenetic congruence between chloroplast and
      mitochondrial haplotypes in Silene vulgaris.
AB  - Both the chloroplast and mitochondrial genomes are used extensively in studies of
      plant population genetics and systematics. In the majority of angiosperms, the
      chloroplast DNA (cpDNA) and mitochondrial DNA (mtDNA) are each primarily
      transmitted maternally, but rare biparental transmission is possible. The extent
      to which the cpDNA and mtDNA are in linkage disequilibrium is argued to be
      dependent on the fidelity of co-transmission and the population structure. This
      study reports complete linkage disequilibrium between cpDNA and mtDNA haplotypes
      in 86 individuals from 17 populations of Silene vulgaris, a gynodioecious plant
      species. Phylogenetic analysis of cpDNA and mtDNA haplotypes within 14
      individuals supports a hypothesis that the evolutionary histories of the
      chloroplasts and mitochondria are congruent within S. vulgaris, as might be
      expected if this association persists for long periods. This provides the first
      documentation of the evolutionary consequences of long-term associations between
      chloroplast and mitochondrial genomes within a species. Factors that contribute
      to the phylogenetic and linkage associations, as well as the potential for
      intergenomic hitchhiking resulting from selection on genes in one organellar
      genome are discussed.

PMID- 12233781
TI  - The ootheca of Mastotermes darwiniensis Froggatt (Isoptera: Mastotermitidae):
      homology with cockroach oothecae.
AB  - The basal termite Mastotermes darwiniensis produces an egg mass, the nature of
      which is controversial. The debate centres on whether it is homologous with the
      oothecae of mantids and cockroaches and, if so, whether its simple structure is
      plesiomorphic or apomorphic within the Dictyoptera. To help resolve these issues
      we observed primary reproductives of M. darwiniensis during oviposition and
      examined the morphology of the reproductive product. Oviposition is cockroach
      like in that the egg mass is assembled within the vestibulum and the eggs are
      issued externally in pairs. The reproductive product is an ootheca of the
      blattarian type. A distinct, tanned outer covering is stretched over the two
      parallel rows of eggs. No keel is present and no calcium oxalate crystals were
      apparent in the outer covering. We cannot rule out the possibility that the
      simple structure of the ootheca is plesiomorphic within Dictyoptera. However,
      based on (i) apomorphies shared by Mastotermes and Blattaria, and (ii) the life
      habits of Isoptera, a secondary reduction is the more plausible explanation.

PMID- 12233782
TI  - Induction of osteogenic protein-1 expression by interleukin-1beta in cultured
      rabbit articular chondrocytes.
AB  - To elucidate the effects of interleukin-1beta (IL-1beta) on osteogenic protein-1
      (OP-1) gene expression in a polylayer culture of rabbit articular chondrocytes,
      we measured rabbit OP-1 mRNA using quantitative TaqMan reverse transcriptase
      polymerase chain reaction (RT-PCR) techniques. Rabbit articular chondrocytes were
      isolated and cultured in minimum essential medium eagle alpha modification
      containing 10% fetal bovine serum for 7 days. IL-1beta was then added and
      cultures were continued for 48 or 96 hours. OP-1 gene expression was detected in
      cell cultures both with and without addition of IL-1beta. However, the level of
      expression was very low in the control group. OP-1 gene expression was
      significantly increased about 450- to 800-fold in IL-1beta-treated groups (0.1,
      1, and 10 ng/ml) versus the control group. Evaluation of serial changes in OP-1
      expression after addition of IL-1beta (10 ng/ml) revealed that OP-1 gene
      expression increased rapidly after addition of IL-1beta, reaching a peak at 48
      hours, and then decreasing. Simultaneous assay of CD44 expression demonstrated a
      rapid increase, similar to that of OP-1 expression, following addition of IL
      1beta: this was followed by a more gradual increase. Assay of hyaluronan synthase
      2 (HAS-2) expression following addition of IL-1beta showed an increase after OP-1
      expression had already reached a peak. Our results demonstrate that OP-1
      expression is induced by IL-1beta and suggest that this expression, like that of
      HAS-2, may play a role as a protective mechanism against inflammatory cytokines.

PMID- 12233783
TI  - Six gray single dose radiotherapy in the treatment of metastatic bone pain.
AB  - Bone metastases are observed in approximately 50% of patients with cancer and
      these are essential to influence the quality of life. As one of the most
      effective means of therapy for patients with bone metastases, radiotherapy can be
      applied as fractional and single dose. In this prospective study, we analyzed the
      pain relief after 6 Gy single dose irradiation in 62 patients with painful bone
      metastases. This was assessed by an 11-point scale questionnaire. In 88.7% of the
      treatments response was obtained after the single-dose radiotherapy (37.1%
      complete response, 51.6% partial response, 11.3% no response). In approximately
      53% of the treatments the response initiated within one week. We concluded that a
      single dose of 6 Gy was very effective in the palliation of painful bone
      metastases.

PMID- 12233784
TI  - Humoral GalNAc alpha1-3GalNAc-lipid reactivity of humans in hypomanic state.
AB  - A glycolipid having GalNAc alpha1-3GalNAc in the terminal increases a behavior
      climbing in a depression model, mouse forced swimming. Antidepressants, which
      sometimes induce hypomanic state in patients, increase the glycolipid and an anti
      manic substance lithium decreases the glycolipid in mice. We detected the humoral
      GalNAc alpha1-3GalNAc-lipid reactivity of humans in different affective states.
      Although the reactivity was also showed in serums of the depression patients and
      the volunteers without affective disorders, the reactivity was remarkably
      increased in serums of hypomania patients. These strongly suggest that the
      humoral glycolipid increased the activities of the hypomania patients, but did
      not relate to the decrease of the activities in the depression patients.

PMID- 12233785
TI  - Lipid peroxidation and antioxidant enzymes in Turkish population: relation to
      age, gender, exercise, and smoking.
AB  - The purpose of this study was to examine the change in lipid peroxidation and
      antioxidant enzyme activities in healthy subjects and to evaluate the
      concentrations of superoxide dismutase, glutathione peroxidase and
      malondialdehyde, an end product of lipid peroxidation in exercise and smoking.
      Study included 257 appearently healthy individuals, 133 males and 124 females. In
      all subjects, malondialdehyde (MDA) levels were analyzed as an indicator of the
      lipid peroxidation activities. Superoxide dismutase, glutathione peroxidase
      activities were measured as an indicator of antioxidant activities. Oxidative
      stress was estimated by the method based on thiobarbituric acid reactivity.
      Erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)
      activities were estimated on hemolysates by use of commercial available kits
      (Randox lab., Dublin, Ireland). For all groups serum lipid peroxidation and
      erythrocyte SOD and GSH-Px were obtained at the initial and the following
      periods. Serum MDA level was higher in the elderly than in the children and in
      the adults. MDA levels were higher in the smoking, acute exercise than their
      counterparts in the control groups. GSH-Px activity was significantly lower in
      the acute exercise group, and higher in the trained group than those as controls.
      SOD decreased in the elderly, smoking and acute exercise groups and increased in
      trained individuals. There was a significant increase in lipid peroxidation
      activity and a significant decrease in antioxidant enzyme activity in cases of
      acute exercise and smoking as well as the elderly.

PMID- 12233786
TI  - Pathogenesis and management of virus infection-induced exacerbation of senile
      bronchial asthma and chronic pulmonary emphysema.
AB  - The number of senile patients with therapy resistant bronchial asthma, chronic
      pulmonary emphysema increases due to the habit of smoking and increased number of
      older people, and these inflammatory pulmonary diseases are the leading causes of
      death worldwide. Rhinoviruses cause the majority of common colds, and provoke
      exacerbations of bronchial asthma and chronic pulmonary emphysema. Here, I review
      the pathogenesis and management of rhinovirus infection-induced exacerbation of
      senile bronchial asthma and chronic pulmonary emphysema.

PMID- 12233787
TI  - Effects of topical mitomycin on inner ear: a light and electron microscopic
      study.
AB  - Providing maintenance of myringotomy patency without use of ventilation tubes in
      the treatment of secretory otitis media has been one of the important study
      areas. For this reason, laser and Mitomycin C (MMC) are used together in
      experimental studies. But there has been no ultrastructural studies concerning
      whether leakage of MMC to middle ear during application of this procedure has an
      ototoxic effect or not and if so, to what extent. In this study, we searched the
      ultrastructural changes which occurred in the middle ear by direct applications
      of MMC to the middle ear for different time durations. The study was carried out
      over thirty adult guinea pigs without ear diseases. Bilateral myringotomy was
      performed and MMC was applied only to the right middle ear of each guinea pig.
      The first group received MMC once for 10 minutes, the second group received it
      once for 20 minutes, and the third group took it each day for 10 minutes during a
      one week period. The left ears of the samples were accepted as the control group.
      On the 8th day, sacrification was carried out. After electron and light
      microscopy examination, significant changes in the inner ear were observed in the
      third group though no significant change was observed for the first and the
      second groups. As a result it was concluded that the application of MMC to the
      middle ear once for a short duration causes no toxic effect on the inner ear.

PMID- 12233788
TI  - Ultrastructural localization of aquaporin 4 and alpha1-syntrophin in the vascular
      feet of brain astrocytes.
AB  - Aquaporin 4 (AQP4) is a recently discovered membrane bound water-selective
      channel and has been described at the light microscopic level to be predominantly
      expressed in the astrocytes of the brain, especially at the perivascular
      astrocyte endfoot processes. Alpha1-syntrophin, a member of dystrophin-associated
      protein, has also been reported at the light microscopic to be expressed level in
      the same site of astrocytes as AQP4 and interacts with other molecules through
      its PDZ domain. AQP4 expression has been reported to be absent at the sarcolemma
      and the perivascular astrocyte endfoot processes of alpha1-syntrophin knockout
      mice. Based on these observations, the molecular association between AQP4 and
      alpha1-syntrophin could be speculated. To test this hypothesis, we investigated
      the ultrasturctural localization of AQP4 and alpha1-syntrophin in the brain
      astrocytes by using double immunogold labeled electron microscopy. The results
      showed that AQP4 and alpha1-syntrophin colocalized frequently at the astrocyte
      membrane, especially at the perivascular astrocyte endfoot processes and
      suggested the presence of linkage between AQP4 and alpha1-syntrophin at the
      astrocyte plasma membrane.

PMID- 12233789
TI  - Clinical characteristics of gestational trophoblastic disease at a single
      institute.
AB  - Gestational trophoblastic diseases (GTD) represent a group of malignancies
      classified as invasive mole, choriocarcinoma, and placental-site trophoblastic
      tumors. The overall cure rate in the treatment of this malignant disorder now
      exceeds 90%. The aim of this study is retrospectively to evaluate the clinical
      characteristics and effectiveness of single-agent chemotherapy (CT) and
      combination chemotherapy according to the World Health Organization (WHO) risk
      groups of gestational trophoblastic diseases. Thirty one patients with GTD were
      treated in our institute between 1990-1998. Median age at presentation was 29
      years (range 19-70 years). All patients were classified with respect to the WHO
      scoring system. According to this system, patients were divided into three
      clinical groups: low-risk nonmetastatic (low-risk group with good prognosis), low
      risk metastatic, and high-risk metastatic (high risk group with poor prognosis).
      Eighteen patients in the nonmetastatic low-risk group with favorable prognostic
      factors received single agent CT (methotrexate and folinic acid), while 3
      patients with metastatic low-risk and 10 patients in the metastatic high-risk
      group with poor prognosis received combination CT (EMA-CO). Complete response
      (CR) was obtained in all patients in the low risk group with good prognosis,
      whereas 9/13 (69%) patients in the poor prognosis group achieved CR and 4 (31%)
      had partial responses. This clinical classification system may be currently
      prefer for determining initial therapy in women with malignant gestational
      trophoblastic tumors. And, our report confirms that the alternating EMA/CO
      regimen is a well-tolerated and effective combination for the treatment of women
      with high-risk GTD.

PMID- 12233790
TI  - Progress notes: Tufts University School of Medicine.

PMID- 12233791
TI  - Micronesian massage and massage oils: ancient practice and contemporary medical
      therapy.

PMID- 12233792
TI  - The precautionary principle: bearing witness to and alleviating suffering.

PMID- 12233793
TI  - Broadening the base: treating people together.

PMID- 12233794
TI  - Nothing.

PMID- 12233796
TI  - Prayer.

PMID- 12233795
TI  - Jin Shin Jyutsu outcomes in a patient with multiple myeloma.

PMID- 12233797
TI  - Effects of ashwagandha in a rat model of stroke.

PMID- 12233798
TI  - Women seek alternatives to hormone replacement therapy.

PMID- 12233799
TI  - The uncertainties of medicine: a cause for celebration.

PMID- 12233800
TI  - When to disbelieve the believable.

PMID- 12233801
TI  - The precautionary principle.

PMID- 12233802
TI  - Lipophil-mediated reduction of toxicants in humans: an evaluation of an ayurvedic
      detoxification procedure.
AB  - CONTEXT: Lipophilic toxicants have been associated with hormone disruption,
      immune system suppression, reproductive disorders, several types of cancer, and
      other diseases. Due to environmental persistence and bioaccumulation, body
      burdens of certain toxicants, such as dichlorodiphenyldichloroethylene (DDE) and
      polychlorinated biphenyls (PCBs), appear to be a health risk despite the
      toxicants' having been banned for decades. OBJECTIVE: To determine whether a
      safe, standardized, Ayurvedic detoxification procedure can mobilize lipid-soluble
      toxicants and stimulate their excretion. DESIGN: Cross-sectional and longitudinal
      evaluations. SETTING: Southeastern Iowa. PARTICIPANTS: In the cross-sectional
      study, 48 participants who had undertaken lipophil-mediated detoxification were
      compared with 40 control subjects. In the prospective, longitudinal evaluation,
      serum levels were measured in 15 subjects before and after they underwent the
      detoxification procedure. These 15 subjects served as their own controls.
      INTERVENTION(S): Ayurvedic lipophil-mediated detoxification procedure. MAIN
      OUTCOME MEASURE: Gas chromatographic analysis of 17 serum toxicant levels (9 PCB
      congeners and 8 pesticides or metabolites) on a lipid-adjusted and wet-weight
      basis (ng/g) as parts per billion. RESULTS: In the cross-sectional study, gas
      chromatographic analysis of 9 PCB congeners and 8 pesticides revealed that serum
      PCB levels were significantly lower in the detoxification subjects than in
      controls. Trans-nonachlor (TNC), p,p'-dichlorodiphenyldichloroethylene (p,p'
      DDE), oxychlordane, and hexachlorobenzene (HCB) levels were also markedly lower
      in the detoxification group. All subjects had undetectable levels of p,p'-DDT,
      lindane, and a-hexachlorocyclohexane (a-HCH). Beta-hexachlorocyclohexane (beta
      HCH) levels were significantly higher in detoxification subjects than in
      controls. In the longitudinal evaluation, after treatment, mean levels of PCBs
      (46%) and beta-HCH (58%) declined significantly in the subjects. CONCLUSIONS: The
      higher beta-HCH levels in the subjects in the longitudinal study appear to be an
      anomaly related to diet. The results of the 2 studies generally suggest that
      lipophil-mediated detoxification may be effective in reducing body burdens of fat
      soluble toxicants. As numerous people worldwide are at risk from high body
      burdens of such lipid-soluble agents, further studies to evaluate this procedure
      appear warranted.

PMID- 12233803
TI  - The effects of harp music in vascular and thoracic surgical patients.
AB  - CONTEXT: Music has been used in the acute clinical care setting as an adjunct to
      current treatment modalities. Previous studies have indicated that some types of
      music may benefit patients by reducing pain and anxiety, and may have an effect
      on physiological measures. OBJECTIVE: To evaluate the scientific foundation for
      the implementation of a complementary therapy, harp playing. The research
      questions for this pilot study were: Does live harp playing have an effect on
      patient perception of anxiety, pain, and satisfaction? Does live harp playing
      produce statistically and clinically significant differences in physiological
      measures of heart rate, systolic and diastolic blood pressure, respiratory rate,
      and oxygen saturation? DESIGN: A prospective, quasiexperimental, repeated
      measures design was used with a convenience sampling. SETTING: Orlando Regional
      Medical Center, Orlando Fla. PATIENTS: Subjects wer eligible for the study if
      they were postoperative and admitted to a hard-wired-bedside-monitored room of
      the Vascular Thoracic Unit within the 3 days of the study period. INTERVENTION: A
      singl e20-minute live harp playing session. MAIN OUTCOME MEASURES: Visual analog
      scales (VAS) were used to measure patient anxiety and pain. Patient satisfaction
      was measured with a 4-item questionnaire. Physiological measures (heart rate,
      systolic and diastolic blood pressure, respiratory rate, and oxygen saturation)
      were recorded from the bedside monitor. METHODS: Visual analog scales (VAS) were
      completed just before harp playing, 20 minutes after harp playing was started,
      and 10 minutes after completion. Patient satisfaction with the experience was
      measured with a 4-item questionnaire. Physiological measures (heart rate,
      systolic and diastolic blood pressure, respiratory rate, and oxygen saturation)
      were recorded from the bedside monitor at baseline (5 minutes before study
      setup), at zero, 5, 10, 15, and 20 minutes after harp playing began, and at 5 and
      10 minutes after harp playing stopped. RESULTS: Seventeen patients were used in
      this study, with a retrospective power of .91. Results indicate that listening to
      live harp music has a positive effect on patient perception of anxiety (P=.000),
      pain (P=.000) and satisfaction. Live harp playing also produced statistically
      significant differences in physiological measures of systolic blood pressure
      (P=.046), and oxygen saturation (P=.011). Although all values over time trended
      downward, the changes of other variables were not adequate to achieve statistical
      or clinical significance. CONCLUSION: Subjects in this study experienced
      decreased pain and anxiety with the harp intervention, and slight reductions in
      physiologic variable values. It is not possible in this study to determine if the
      results were due to the harp music, the presence of the harpist and data
      collector, or both. Future research is recommended using a control group and
      comparison of live versus recorded harp music with a wider variety of diagnoses
      and procedures.

PMID- 12233804
TI  - Testing the bioelectric shield.
AB  - A pendant was claimed to provide numerous health benefits, including reduced
      stress, increased strength, and protection from electromagnetic radiation from
      computers and mobile phones. Three experiments tested the effectiveness of this
      pendant's effect as a bioelectric shield. In the first experiment, 12 subjects
      who work with computers wore shields (6 real, 6 sham) for several weeks and were
      regularly tested for hand strength and mood changes. Both types of shield
      increased calmness, but the real shields did not have any greater effect. In 2
      further studies (in each N=40) hand strength was measured at baseline, with
      mobile phone, and with mobile phone and bioelectric or sham shield. The shields
      did not differ in their effects. Both studies showed a significant correlation
      between the change in strength with and without the shield and subjects'scores on
      a questionnaire concerning their belief in and use of alternative therapies. The
      shields appear to produce a measurable placebo effect but are otherwise
      ineffective.

PMID- 12233805
TI  - Complementary and alternative medical treatment of breast cancer: a survey of
      licensed North American naturopathic physicians.
AB  - CONTEXT: Complementary and alternative medicine (CAM) use is on the rise in the
      United States, especially for breast cancer patients. Many CAM therapies are
      delivered by licensed naturopathic physicians using individualized treatment
      plans. OBJECTIVE: To describe naturopathic treatment for women with breast
      cancer. DESIGN: Cross-sectional mail survey in 2 parts: screening form and 13
      page survey. SETTING: Bastyr University Cancer Research Center, Kenmore, Wash.
      PARTICIPANTS: All licensed naturopathic physicians in the United States and
      Canada (N=1,356) received screening forms; 642 (47%) completed the form. Of the
      respondents, 333 (52%) were eligible, and 161 completed the survey (48%). MAIN
      OUTCOME MEASURES: Demographics of naturopathic physicians, development of
      treatment plans, CAM therapies used, perceived efficacy of therapeutic
      interventions. RESULTS: Of those respondents screened, 497 (77%) had provided
      naturopathic care to women with breast cancer, and 402 (63%) had treated women
      with breast cancer in the previous 12 months. Naturopaths who were women were
      more likely than men to treat breast cancer (P < or = .004). Of the survey
      respondents, 104 (65%) practiced in the United States, and 57 (35%) practiced in
      Canada; 107 (66.5%) were women, and 54 (33.5%) were men. To develop naturopathic
      treatment plans, naturopathic physicians most often considered the stage of
      cancer, the patient's emotional constitution, and the conventional therapies
      used. To monitor patients clinically, 64% of the naturopathic physicians used
      diagnostic imaging, 57% considered the patient's quality of life, and 51% used
      physical examinations. The most common general CAM therapies used were dietary
      counseling (94%), botanical medicines (88%), antioxidants (84%), and supplemental
      nutrition (84%). The most common specific treatments were vitamin C (39%),
      coenzyme Q-10 (34%), and Hoxsey formula (29%).

PMID- 12233806
TI  - Greening healthcare: practicing as if the natural environment really mattered.
AB  - OBJECTIVE: The natural world's role in human well-being is an essential, yet
      often forgotten, aspect of healthcare. Of particular importance are the benefits
      one can derive through interaction with natural environments. While health is an
      obvious goal of allopathic medicine, many healthcare settings are neither
      nurturing nor healing. Reincorporating the natural world into the design of
      settings in which medicine is practiced is one way to complement conventional
      healing modalities and move healthcare toward being more "green." This article
      discusses the breadth of existing knowledge available on the positive aspects of
      interaction with nature and provides a comprehensive theoretical perspective for
      future research. DATA SOURCES: Computerized searches were conducted using
      MEDLINE, PsycINFO, the Social and Scientific Science Indices, Dissertation
      Abstracts, Lexus-Nexus, the University of Michigan library, and the Internet.
      Searches were conducted from June 2001 through March 2002. STUDY SELECTION:
      Keywords used included health, well-being stress, attention, nature, garden,
      landscape, restorative, and healing. The literature, published between 1960 and
      2001, came from various disciplines, including medicine, public health, nursing
      psychology, natural resources, history, and landscape architecture. Four
      components of well-being were used as a framework for literature selection:
      physical psychological-emotional social, and spiritual. DATA EXTRACTION: Articles
      were qualitatively reviewed to extract theories, hypotheses, and experimental
      evidence. DATA SYNTHESIS: Interaction with nature positively affects multiple
      dimensions of human health. Physiological effects of stress on the autonomic
      nervous system are lessened. Psychologically, deficits in attention can be
      restored or minimized, and people report feeling greater satisfaction with a
      variety of aspects of life. The presence of the natural world promotes social
      health by encouraging positive social interaction and lessening the frequency of
      aggressive behavior. Spiritual well-being is enhanced through the experience of
      greater interconnectedness, which occurs when interacting with the natural world.
      CONCLUSIONS: The literature reviewed provides evidence to support the intuitive
      belief that interaction with the natural world is a vital part of biopsychosocial
      spiritual well-being. Incorporating the natural world into healthcare could
      provide health benefits and improve the design of healthcare facilities. Applied
      more broadly to society, this knowledge may change the way we approach public
      health, guard and manage natural resources, and design environments for human
      use.

PMID- 12233808
TI  - Ginger syrup as an antiemetic in early pregnancy.
AB  - CONTEXT: Ginger (Zingiber officinale) has been used to ameliorate symptoms of
      nausea. A beverage containing ginger in a syrup may be easier to consume than a
      capsule or solid food. OBJECTIVE: To determine if ginger syrup mixed in water is
      an effective remedy for the relief of nausea and vomiting in the first trimester
      of pregnancy. DESIGN: Double-blind, placebo-controlled, randomized clinical
      trial. SETTING: Subjects were enrolled from the University of South Florida
      department of obstetrics and gynecology private practice office. PATIENTS: 26
      subjects in the first trimester of pregnancy. INTERVENTION: Subjects ingested 1
      tablespoon of commercially prepared study syrup (or placebo) in 4 to 8 ounces of
      hot or cold water 4 times daily. MAIN OUTCOME MEASURES: Duration and severity of
      nausea and vomiting over a 2-week period measured on a 10-point scale. RESULTS:
      After 9 days, 10 of the 13 (77%) subjects receiving ginger had at least a 4-point
      improvement on the nausea scale. Only 2 of the 10 (20%) remaining subjects in the
      placebo group had the same improvement. Conversely, no woman in the ginger group,
      but 7 (70%) of the women in the placebo group, had a 2-point or less improvement
      on the nausea scale. Eight of the 12 (67%) women in the ginger group who were
      vomiting daily at the beginning of the treatment stopped vomiting by day 6. Only
      2 of the 10 (20%) women in the placebo group who were vomiting stopped by day 6.
      CONCLUSION: The ingestion of 1 g of ginger in syrup in a divided dose daily may
      be useful in some patients experiencing nausea and vomiting in the first
      trimester of pregnancy.

PMID- 12233807
TI  - Leech therapy for symptomatic treatment of knee osteoarthritis: results and
      implications of a pilot study.
AB  - CONTEXT: Leech therapy was a mainstay in conventional treatment for pain from
      antiquity until the mid-19th century. Its use is still widespread in traditional
      healing procedures in Asia, Africa, and Arabic countries. There is renewed
      interest in leech therapy in the field of complementary medicine and empirical
      evidence for specific benefit in knee osteoarthritis. OBJECTIVES: To determine
      the effect of leech therapy as an adjunctive treatment in painful knee
      osteoarthritis, to investigate the onset of action, to evaluate patients'
      acceptance of this treatment, and to investigate the side effects of the
      procedure. DESIGN: Observational, controlled, nonrandomized pilot-study. SETTING:
      Subjects were inpatients of an academic teaching hospital of the University of
      Essen, Department of Internal and Integrative Medicine, Essen, Germany. PATIENTS:
      16 inpatients (mean age 69 +/- 9 years) with a confirmed diagnosis of
      osteoarthritis of the knee joint; 10 patients were treated with leeches and 6
      served as controls. INTERVENTION: A single trial of 4 leeches (Hirudo
      medicinalis) applied topically at painful periarticular sites of the knee joint
      in the experimental group (n = 10). Both groups received conventional treatment
      for pain with the exclusion of nonsteroidal anti-inflammatory drugs. MAIN OUTCOME
      MEASURES: Self-reported general knee pain, assessed by visual analog scale for 10
      days daily and in a follow-up after 28 days. Frequency of adverse effects also
      was recorded. RESULTS: Periarticular application of 4 leeches led to rapid relief
      of pain with sustained improvement after 4 weeks in the absence of major
      complications. CONCLUSION: Leech therapy may be an effective treatment for rapid
      reduction of pain associated with osteoarthritis of the knee. Its efficacy should
      be tested in larger randomized controlled trials with assessment of expectation
      bias.

PMID- 12233809
TI  - Kenny Ausubel: ecological medicine: interview by Bonnie Horrigan.

PMID- 12233810
TI  - Nitric oxide synthase gene therapy for cardiovascular disease.
AB  - Gene therapy refers to the transfer of specific genes to the host tissue to
      intervene in a disease process, with resultant alleviation of the symptoms of a
      particular disease. Cardiovascular gene transfer is not only a powerful technique
      for studying the function of specific genes in cardiovascular biology and
      pathobiology, but also a novel and promising strategy for treating cardiovascular
      diseases. Since the mid-1990s, nitric oxide synthase (NOS), the enzyme that
      catalyzes the formation of nitric oxide (NO) from L-arginine, has received
      considerable attention as a potential candidate for cardiovascular gene therapy,
      because NO exerts critical and diverse functions in the cardiovascular system,
      and abnormalities in NO biology are apparent in a number of cardiovascular
      disease processes including cerebral vasospasm, atherosclerosis, postangioplasty
      restenosis, transplant vasculopathy, hypertension, diabetes mellitus, impotence
      and delayed wound healing. There are three NOS isoforms, i.e., endothelial
      (eNOS), neuronal (nNOS) and inducible (iNOS). All three NOS isoforms have been
      used in cardiovascular gene transfer studies with encouraging results. This
      review will discuss the rationale of NOS gene therapy in different cardiovascular
      disease settings and summarize the results of experimental NOS gene therapy from
      various animal models of cardiovascular disease to date.

PMID- 12233811
TI  - Transcription factors and drugs in the brain.
AB  - In mammalian cells, protein de novo synthesis is mainly regulated at the stage of
      gene transcription by RNA polymerase II in the nucleus. Transcription factors are
      proteins that bind to the specific nucleotide sequences at promoter or enhancer
      regions on target genes to control the transcription of mRNA from genomic DNA. In
      this article, we have outlined the signal responsiveness of different
      transcription factors to particular drugs in the brain. Nuclear transcription
      factors rapidly respond to a variety of extracellular signals carried by
      neurotransmitters, hormones and autacoids as a third messenger in frequent
      situations. Translated proteins are responsible for a number of physiological and
      pathological events for a long period in the brain. We have also discussed
      possible involvement of transcription factors in molecular mechanisms underlying
      development of tolerance and dependence to drugs following acute and chronic
      administration.

PMID- 12233813
TI  - Possible involvement of M5 muscarinic receptor in the enhancing actions of the
      novel gastroprokinetic agent Z-338 on nifedipine-sensitive voltage-dependent Ca2+
      currents in guinea pig stomach.
AB  - We investigated the effects of the novel gastroprokinetic agent Z-338 (N-(N-N'
      diisopropylaminoethyl)-[2-(2-hydroxy-4,5-dimethoxybenzoylamino)-1,3-thiazole-4
      yl] carboxyamide monohydrochloride trihydrate) on L-type voltage-dependent Ca2+
      currents (ICa) in guinea pig gastric myocytes by using the whole-cell patch clamp
      technique. Bath-applied acetylcholine (ACh) produced biphasic effects on ICa,
      i.e., enhancement (1-100 nM) and inhibition (1-100 microM), both of which were
      abolished by pretreatment with atropine (10 microM) or intracellular perfusion of
      GDPbetaS (500 microM). Z-338 (> or = 1 nM, ED50: 120 nM) mimicked the enhancing
      effects of ACh, but did not inhibit ICa. The effects of Z-338 and ACh were non
      additive and blocked by atropine and GDPbetaS, but not by pertussis toxin (PTX)
      pretreatment (500 ng/ml). ACh (> or = 1 microM) induced slow inward currents via
      activation of the muscarinic receptor/PTX-sensitive G-protein pathway, but Z-338
      was devoid of these effects. Neither pirenzepine (1 microM), AF-DX116 (1 microM),
      nor oxybutynin (100 nM) could prevent Z-338 (1 microM) and ACh (10 nM) from
      enhancing ICa, whilst 4-DAMP (100 nM) blocked the effects of Z-338 and ACh. Bath
      application of protein kinase C (PKC) activator PDBu (phorbol-12,13-dibutyrate)
      (250 nM) enhanced ICa, and conversely, pipette inclusion of PKC inhibitor peptide
      (150 microM) abolished the effects of ACh and Z-338 on ICa. These results
      collectively suggest that although contribution of the M3 receptor is not
      excluded, the major actions of Z-338 on gastric myocytes are potentiation of ICa
      through activation of M5-like receptor.

PMID- 12233812
TI  - 5-Hydroxytryptamine receptors, especially the 5-HT4 receptor, in guinea pig
      urinary bladder.
AB  - The function of 5-hydroxytryptamine (5-HT) receptors, especially the 5-HT4
      receptor, in the urinary bladder were examined in preparations isolated from the
      guinea pig by in vitro receptor autoradiography and determinations of mechanical
      activity and acetylcholine (ACh) release. Specific [125I]SB207710 binding sites
      were detected evenly throughout the urinary bladder. 5-HT (3 x 10(-8)-10(-4) M)
      caused contractions of strips of the urinary bladder, in a concentration
      dependent manner. Ketanserin antagonized the 5-HT-induced contractions, while
      granisetron and SB204070 antagonized the contractions induced by high
      concentrations of 5-HT. Atropine inhibited the contractions induced by high
      concentrations of 5-HT. Ketanserin prevented the 5-HT-induced contractions in the
      presence of atropine, but granisetron and SB204070 did not affect the
      contractions under such a condition. 5-HT enhanced the electrically-stimulated (5
      Hz, 0.5 ms) outflow of [3H]acetylcholine from strips preloaded with [3H]choline,
      and the enhancement was antagonized by granisetron and SB204070. Thus, the
      contractile response to 5-HT was mediated by activations of 5-HT2, 5-HT3 and 5
      HT4 receptors. The 5-HT2 receptor may be a property of high affinity to 5-HT and
      located on the smooth muscle cells. The 5-HT4 as well as 5-HT3 receptor may be a
      property of low affinity to 5-HT and located on the cholinergic neurons.

PMID- 12233814
TI  - A1 and A2 adenosine receptor activation inversely modulates potassium currents
      and membrane potential in DDT1 MF-2 smooth muscle cells.
AB  - Adenosine receptors are widely distributed in mammalian tissues and have been
      possibly involved through transmembrane potential changes in cell function
      regulation. The effect of A1 and A2A adenosine receptor ligands on transmembrane
      potential measured with flow cytometry and potassium conductance measured by the
      patch-clamp technique was investigated in DDT1 MF-2 smooth muscle cells. The A1
      adenosine-receptor agonist CPA (50 nM) and the A2A adenosine-receptor agonist CGS
      21680 (50 nM) elicited a rapid and maintained increase and decrease in the
      potassium conductance, respectively, and a concomitant hyperpolarization and
      depolarization of the membrane, respectively. These effects were eliminated by
      subtype-selective adenosine receptor antagonists (DPCPX, CSC, ZM 241385, all 1
      microM). The ligand induced membrane potential changes were reversible. Based on
      these detected membrane potential changes along with the published voltage
      dependence of the adenylyl cyclase, the regulation of cAMP production by A1- and
      A2A-receptor activation is suggested to be mediated through the induced early
      hyperpolarization and depolarization. The interaction between the effects of
      these receptor subtypes allows for a complex regulation mechanism.

PMID- 12233815
TI  - Induction of cyclooxygenase-2 expression in glomeruli by aggregated protein.
AB  - Cyclooxygenase has two isozymes, a constitutive type (cyclooxygenase-1) and an
      inducible type (cyclooxygenase-2). The aim of the present study was to determine
      whether cyclooxygenase-2 is associated with the increased production in
      prostaglandin E2 in glomeruli by aggregated protein. Mice were injected with
      aggregated bovine serum albumin. Glomeruli were isolated using sieves and a
      magnet. Production of prostaglandin E2 was increased in glomeruli after injection
      of aggregated bovine serum albumin. RT-PCR analysis indicated enhanced expression
      of cyclooxygenase-2 mRNA in aggregated bovine serum albumin-loaded glomeruli.
      Western blotting analysis indicated an increase in cyclooxygenase-2 protein in
      glomeruli by aggregated bovine serum albumin. Glomeruli were incubated with
      indomethacin, NS-398 or niflumic acid in the presence of arachidonic acid.
      Indomethacin resulted in remarkable reduction of prostaglandin E2 levels in
      aggregated bovine serum albumin-loaded glomeruli. Niflumic acid also inhibited
      prostaglandin E2 production, and its inhibitory rate was more than that of NS
      398. In conclusion, aggregated protein induces cyclooxygenase-2 in glomeruli,
      suggesting that cyclooxygenase-2 is involved in the process of disposal of
      aggregated protein in glomeuli.

PMID- 12233816
TI  - Vasorelaxing effect of mesaconitine, an alkaloid from Aconitum japonicum, on rat
      small gastric artery: possible involvement of endothelium-derived hyperpolarizing
      factor.
AB  - Aconiti tuber, roots of aconite (Aconitum japonicum), has been used for centuries
      in Japan and China to increase peripheral body temperature. We previously
      reported that mesaconitine, an alkaloid from Aconitum japonicum, elicits
      endothelium-dependent and nitric oxide-mediated relaxation in isolated rat aorta.
      In the present study, we investigated the effect of mesaconitine on isolated rat
      small gastric arteries. Mesaconitine elicited a concentration-dependent (10, 30,
      100 microM) vasorelaxation in isolated rat gastric artery precontracted with
      norepinephrine, which was resistant to N(omega)-nitro-L-arginine (L-NNA) (an
      inhibitor of nitric oxide synthase) and indomethacin (an inhibitor of
      cyclooxygenase). The L-NNA- and indomethacin-resistant relaxation by mesaconitine
      was mainly endothelium-dependent, inhibited by high K+ (30 mM), and inhibited by
      a combination of Ca2+-dependent K channel blockers, charybdotoxin and apamin. The
      relaxation by mesaconitine was proportional to the external Ca2+ concentration.
      These results suggest that mesaconitine elicits vasorelaxation of isolated rat
      small gastric artery mainly via release of endothelium-derived hyperpolarizing
      factor.

PMID- 12233817
TI  - Involvement of gamma-aminobutyric acid (GABA) B receptors in the hypotensive
      effect of systemically administered GABA in spontaneously hypertensive rats.
AB  - We investigated the effects of intraduodenally (i.d.) administered gamma
      aminobutyric acid (GABA) on blood pressure (BP) in anesthetized spontaneously
      hypertensive rats (SHR) and the mechanism underlying this effect, especially the
      type of GABA receptor involved in the depressive effect of this amino acid. GABA
      (0.3 to 300 mg/kg, i.d.) caused a dose-related decrease in the BP of 9.20 +/-
      3.96 to 35.0 +/- 5.34 mmHg (mean +/- S.E.M.) that lasted for 30 to 50 min. The
      minimum effective i.d. dose of GABA was 0.3 to 1.0 mg/kg. Results pertaining to
      the mechanism underlying the GABA-induced effects on BP were as follows: a) GABA
      did not alter the BP-related effects of exogenous noradrenaline and
      acetylcholine; b) pretreatment with hexamethonium decreased the GABA-induced fall
      in BP, and GABA tended to reduce the pressor response associated with injection
      of dimethyl phenylpiperazinium; and c) pretreatment with 2-hydroxysaclofen
      markedly reduced the GABA-induced drop in BP, whereas pretreatment with
      bicuculline did not. In conclusion, in SHR, low-dose (0.3 to 1.0 mg/kg, i.d.)
      GABA had a hypotensive effect, which may result from attenuation of sympathetic
      transmission through the activation of GABA(B) receptors at presynaptic or
      ganglionic sites.

PMID- 12233818
TI  - Rebound contraction by nitric oxide in the longitudinal muscle of porcine gastric
      fundus.
AB  - The rebound contraction induced by electrical field stimulation (EFS) and nitric
      oxide (NO) donor, S-nitroso-L-cysteine (cysNO), were investigated in the
      longitudinal muscle of porcine gastric fundus (LM-PGF). Under the presence of
      atropine and guanethidine, cysNO and EFS produced sequential relaxation
      contraction in LM-PGF. Tetrodotoxin abolished the EFS-induced response, while
      leaving the cysNO-induced one unaffected. A soluble guanylate cyclase inhibitor,
      1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one, inhibited both cysNO and EFS
      induced biphasic response. A cGMP analogue only relaxed LM-PGF. A
      phosphodiesterase V inhibitor, zaprinast, prolonged the cysNO and the EFS-induced
      relaxation and inhibited the rebound contraction. The rebound contraction was
      inhibited by verapamil, an L-type Ca2+ channel blocker. The cysNO and the EFS
      induced biphasic response were inhibited by ryanodine plus cyclopiazonic acid or
      by ruthenium red, a ryanodine-receptor blocker. LM-PGF was relaxed on exposure to
      caffeine and then produced a verapamil-sensitive rebound contraction during the
      washout period. CysNO and EFS did not induce the rebound contraction in the
      presence of caffeine. These results suggest that the NO-induced rebound
      contraction involves both Ca2+-release from the ryanodine-sensitive store and
      Ca2+-influx through L-type channels. Although the NO-induced biphasic response is
      dependent on cGMP, rapid removal of cGMP seems necessary for the rebound
      contraction.

PMID- 12233819
TI  - Effects of sarpogrelate, a novel 5-HT2 antagonist, on 5-HT-induced endothelium
      dependent relaxations in porcine coronary artery.
AB  - The aim of the present study was to examine the effects of sarpogrelate, a 5-HT2
      antagonist, on 5-HT-induced endothelium-dependent relaxation in isolated porcine
      coronary artery preincubated with ketanserin (3 x 10(-6) M) and precontracted by
      U 46619 (5 x 10(-9) M) and compare its effects with other 5-HT2 antagonists such
      as ritanserin and cyproheptadine. The investigation showed that sarpogrelate (10(
      7)-10(-5) M) had a weak antagonistic effect on 5-HT-induced relaxation and its
      effect was weaker than that of ritanserin (10(-9)-10(-7) M) and cyproheptadine
      (10(-8)-10(-6) M). The rank order of the antagonistic effects was: ritanserin >
      cyproheptadine > sarpogrelate. The study also showed that both sarpogrelate and
      ritanserin had no inhibitory effect on bradykinin-induced relaxation. In our
      previous study, we investigated the binding affinity of sarpogrelate, ritanserin
      and cyproheptadine to the 5-HT2A-receptor in rabbit cerebral cortex membranes and
      the pKi values found were 7.22, 8.98 and 7.54, respectively (M. Rashid et al.,
      Jpn J Pharmacol 87, 189-194, 2001). Rank order of the calculated ratio of
      concentration of pA2 or pD'2 vs Ki was: sarpogrelate > ritanserin >
      cyproheptadine. Thus, these findings suggest that sarpogrelate has the lowest
      antagonistic effect on 5-HT-induced endothelium-dependent relaxation and the
      highest selectivity towards 5-HT2A receptor and might also be the safest drug
      with respect to its clinical implications in comparison with ritanserin and
      cyproheptadine.

PMID- 12233820
TI  - DNA microarray analysis of differentially expressed genes responsive to bisphenol
      A, an alkylphenol derivative, in an in vitro mouse Sertoli cell model.
AB  - To identify genes elicited by bisphenol A (BPA) in Sertoli cells, we carried out
      a microarray analysis of TTE3 cells (a mouse Sertoli cell line) treated with BPA.
      BPA (100, 200 and 400 microM) induced cell death concentration-dependently, with
      levels being 25%, 33% and 96%, respectively. Of the 1,081 genes analyzed, 3 genes
      showed decreased levels of expression while the remaining 10 genes showed
      increased levels in the cells treated with a subtoxic dose of BPA (200 microM).
      The expressions of six genes were confirmed by the TaqMan assay. These findings
      suggest that DNA microarray analysis is a useful tool for investigating the
      molecular mechanisms of the toxic effects of BPA in testicular cells.

PMID- 12233821
TI  - Induction of apoptosis in a human breast cancer cell overexpressing ErbB-2
      receptor by alpha-tocopheryloxybutyric acid.
AB  - The overexpression of ErbB-2 receptor relates to malignant transformation of
      breast cancer. The present study was carried out to establish the usefulness of
      alpha-tocopheryloxybutyric acid (TE) as a chemotherapeutic agent for human breast
      cancer. TE caused induction of apoptosis in MDA-MB-453 cells overexpressing the
      ErbB-2 receptor. TE reduced levels of activated ErbB-2 receptor and Akt. In
      contrast, TE induced the activation of p38, and SB203580, a specific inhibitor
      for p38, attenuated the TE-induced apoptosis. These data indicate that
      simultaneous occurrences of Akt inhibition and p38 activation by TE result in the
      cell death.

PMID- 12233822
TI  - Effect of 6-hydroxydopamine treatment in the area postrema on morphine-induced
      emesis in ferrets.
AB  - To investigate the role of catecholamine release in emesis, we examined the
      effects of pretreatment with 6-hydroxydopamine (6-OH-DA) administered into the
      area postrema in morphine-induced emesis in ferrets. In the 6-OH-DA pre-treated
      animals, the latency to the first emetic response induced by morphine
      hydrochloride (1.0 mg/kg, s.c.) was significantly prolonged and the number of
      retches and emetic episodes was markedly reduced. In the medulla oblongata, the
      levels of dopamine and homovanilic acid were reduced by 6-OH-DA pretreatment.
      These results suggest that catecholamine release in the medulla oblongata, mainly
      dopamine release, may play an important role in morphine-induced emesis in
      ferrets.

PMID- 12233823
TI  - Brain extraction of 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4
      oxobutyl]pyridinium ion (HPP+), a neurotoxic metabolite of haloperidol: studies
      using [3H]HPP+.
AB  - Tritium-labeled 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]pyridinium
      ion (HPP+) was synthesized enzymatically from [3H]haloperidol using rat liver
      microsomal preparations, and using prepared [3H]HPP+, the passage of HPP+ into
      the brain was investigated. Consequently, HPP+ showed a moderate brain uptake
      index, indicating that it is able to permeate the blood-brain barrier.
      Furthermore, HPP+ was detected in murine brains after being intravenously
      injected. These results suggested that HPP+, produced mainly in the liver, is
      taken up into the brain and induces damage to brain dopaminergic neurons.

PMID- 12233824
TI  - Effects of L-765,314, a selective and potent alpha 1B-adrenoceptor antagonist, on
      periarterial nerve electrical stimulation-induced double-peaked constrictor
      responses in isolated dog splenic arteries.
AB  - The periarterial nerve electrical stimulation (PNS) at a frequency of 1 or 4 Hz
      (30-s trains of pulses) readily caused a double peaked vasoconstriction in the
      canine splenic artery. The treatment with 1 microM L-765,314, a selective and
      potent alpha1B-adrenoceptor antagonist, markedly inhibited the second peaked
      constriction, whereas it did not modify the vasoconstrictor responses to
      exogenous noradrenaline (0.03-1 nmol) and A61603 (1-30 pmol), a selective alpha1A
      agonist. A large dose of 10 microM L-765,314 significantly blocked exogenous
      noradrenaline- and A61603-induced responses. It is concluded that PNS-induced
      responses are mediated via the postjunctional alpha1B-adrenoceptor subtype.

PMID- 12233825
TI  - Long-term outcome of 56 dogs with nasal tumours treated with four doses of
      radiation at intervals of seven days.
AB  - A retrospective study was undertaken on 56 dogs treated for nasal tumours by
      megavoltage radiotherapy with a hypofractionated schedule consisting of four
      doses of 9 Gy given at intervals of seven days. The dogs were followed until they
      died or were euthanased. The clinical signs had improved in 53 of the 56 dogs by
      the end of the treatment schedule. Mild acute radiation side effects were
      observed in the majority of the dogs but late radiation side effects were rare.
      Kaplan-Meier survival analysis revealed a median survival time after the final
      dose of radiation of 212 days. The one- and two-year survival rates were 45 per
      cent and 15 per cent. Fifty of the dogs were euthanased because the initial
      clinical signs recurred.

PMID- 12233826
TI  - Evaluation of the SNAP foal IgG test for the semiquantitative measurement of
      immunoglobulin G in foals.
AB  - The SNAP Foal IgG test (IDEXX) as evaluated for its accuracy and usefulness by
      measuring blood samples collected from 42 foals between 24 and 48 hours after
      birth. The results were compared with the single radial immunodiffusion (SRID)
      test as the reference method. The SNAP test was quick and easy to perform, and
      the results were similar to those obtained by SRID in 64 per cent of the samples.
      The best results were found with low (< 400 mg/dl) and high (> 800 mg/dl)
      concentrations of immunoglobulin G, with an accuracy of 80 per cent and 89 per
      cent, respectively. The intermediate concentrations were usually lower when
      measured by the SNAP test than by the SRID test, possibly owing to the variable
      volume of blood added to the test with the sample loop.

PMID- 12233827
TI  - Effect of insulin, transferrin and selenium and epidermal growth factor on
      development of buffalo oocytes to the blastocyst stage in vitro in serum-free,
      semidefined media.
AB  - The in vitro development of buffalo oocytes up to the blastocyst stage was
      studied in serum-free, semidefined media containing bovine serum albumin,
      follicle-stimulating hormone (FSH), insulin, transferrin and selenium (ITS) and
      epidermal growth factor (EGF). In experiment 1, oocytes aspirated from abattoir
      derived ovaries were cultured in eight serum-free, semidefined culture media
      containing different combinations of these four factors. In experiment 2, the
      maturation of buffalo oocytes and the development of the embryos were compared in
      a complex co-culture system and in the serum-free, semidefined media.
      Supplementation with FSH and EGF significantly (P < 0.05) increased the
      maturation rates of buffalo oocytes, and the yield of blastocysts was higher (P <
      0.05) in media containing EGF and ITS. The yield of blastocysts was lower in the
      serum-free semidefined media (P < 0.05) than in the complex co-culture system.

PMID- 12233828
TI  - Intraocular pressure and tear production in five herbivorous wildlife species.
AB  - The intraocular pressure and rate of tear production were measured in 18 addax
      antelopes (Addax nasomaculatus), four impalas (Aepyceros melampus), 11 wide
      lipped rhinoceroses (Ceratotherium simum), 10 white-tailed wildebeests
      (Connochaetes gnou) and seven scimitar-horned oryxes (Oryx dammah). The animals
      were anaesthetised with an intramuscular injection of etorphine hydrochloride and
      acepromazine maleate, and the Schirmer tear test I was used to evaluate tear
      production, and applanation tonometry was used to evaluate the intraocular
      pressure. The mean (sd) rate of tear production ranged from 17.6 (3.1) mm/minute
      in the rhinoceros to 28.8 (8.3) mm/minute in the addax. The intraocular pressure
      ranged from 8.0 (1.2) mmHg in the impala to 32.1 (10.4) mmHg in the rhinoceros.
      The rate of tear production in the addax and the intraocular pressure in the
      rhinoceros appear to be the highest values of these variables to have been
      reported in any species.

PMID- 12233829
TI  - Patterns of equine faecal egg counts following spring dosing with either
      fenbendazole or moxidectin.

PMID- 12233830
TI  - Outbreak of malignant catarrhal fever in brown brocket deer (Mazama gouazoubira)
      in Brazil.

PMID- 12233831
TI  - Isolation of Brucella abortus biovar 1 from cattle and water buffaloes on
      Trinidad.

PMID- 12233832
TI  - Withdrawal times for medicines on organic farms.

PMID- 12233833
TI  - BVA governance.

PMID- 12233834
TI  - BVA governance.

PMID- 12233835
TI  - Atypical actinobacillosis in a dairy replacement herd.

PMID- 12233844
TI  - Incidence of Escherichia coli O157:H7 in frozen beef patties produced over an 8
      hour shiftt.
AB  - A ground beef patty processor detected Escherichia coli O157:H7 in five
      production lots during routine testing with polymerase chain reaction (PCR)
      technology. This finding stimulated research to determine the incidence and
      potential entry points of the pathogen during processing. One of these lots
      (53,960 kg) was divided into 71 pallets (760 kg each) of food service ground beef
      patties. Ten cartons (19 kg each) were removed from each pallet, for a total of
      710 cartons. Four patties were taken from each carton and subdivided to provide
      comparable samples for E. coli O157:H7 analyses by three different laboratories.
      Two laboratories employed different immunoassay tests, and one used PCR to screen
      samples. One sample set was analyzed for aerobic plate, coliform, and E coli
      Biotype I counts to determine if any relationship existed between these microbial
      groups and the incidence of E. coli O157:H7. For 73 samples, presumptive positive
      results for E. coli O157:H7 were obtained by one or more methods. For 48 of these
      73 samples, positive results for the pathogen were culture confirmed. The largest
      number (29) of culture-confirmed positive E. coli O157:H7 results were detected
      by PCR. Most positive results were obtained during a short segment of processing.
      All culture-confirmed E. coli O157:H7 strains were further characterized by two
      genetic subtyping techniques, resulting in two to four different patterns,
      depending on the subtyping procedure employed. For any sample tested, the aerobic
      plate count was < 3.0 log CFU/g, and coliform and E. coli Biotype I counts were <
      or = 1.00 log CFU/g. The results of this study suggest that most positive samples
      were associated with a contaminated batch of raw material introduced just before
      the 1725- to 1844-h processing segment. These results also indicate that more
      aggressive sampling plans and genetic screening technologies such as PCR may be
      used to better detect low levels of E. coli O157:H7 in ground beef products.

PMID- 12233845
TI  - Detection and quantitation of enterohemorrhagic Escherichia coli O157, O111, and
      O26 in beef and bovine feces by real-time polymerase chain reaction.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O157:H7 and certain non-O157 EHEC
      serotypes (such as O26:H11, O26: NM, O11:H8, and O111:NM) have emerged as
      significant causes of human disease throughout the world. Important virulence
      attributes of EHEC are the intimin protein (encoded by the eae gene) and Shiga
      toxins 1 and 2 (encoded by the stx1 and stx2 genes, respectively). Two sets of
      real-time polymerase chain reaction (R-PCR) assays were developed for the
      simultaneous detection and quantitation of EHEC through the monitoring of the
      presence of the eae and stx genes, and these assays were evaluated. In the eaeR
      PCR assay, three sets of primers and TaqMan probes were designed for the
      amplification and real-time detection of a portion of the eae gene specific to
      the EHEC O26, O111, and O157 serotypes. In the stxR-PCR assay, two sets of
      primers and TaqMan probes were used to amplify and detect the stx1 and stx2
      genes. DNA prepared from 67 bacterial strains carrying known virulence markers
      was tested to determine the specificities of the two assays. In the eaeR-PCR
      assay, eaeO157- and eaeO111-specific primer-probe sets identified only EHEC O157
      and O111 strains, respectively. The eaeO26-specific primer-probe set identified
      all EHEC 026 isolates and some Shiga toxin-negative serotypes of enteropathogenic
      E. coli and rabbit diarrheagenic E. coli. The stxR-PCR assay was able to identify
      only those strains carrying either or both of the Shiga toxin-encoding genes. The
      detection range of both R-PCR assays was linear over DNA concentrations
      corresponding to 10(3) to 10(8) CFU/ml of an EHEC strain. Both assays were able
      to detect and quantify very low levels (1 to 10 CFU/g of food or feces) of EHEC
      in feces and ground beef enriched for 16 h in a modified Trypticase soy broth. In
      conclusion, eae- and stx-based R-PCR assays are reliable and sensitive methods
      for the rapid screening and specific and quantitative detection of important
      serotypes of EHEC in cattle and in foods of bovine origin.

PMID- 12233846
TI  - Selection of recently isolated colicinogenic Escherichia coli strains inhibitory
      to Escherichia coli O157:H7.
AB  - Escherichia coli strains were screened for their ability to inhibit E. coli
      O157:H7. An initial evaluation of 18 strains carrying previously characterized
      colicins determined that only colicin E7 inhibited all of the E. coli O157:H7
      strains tested. A total of 540 strains that had recently been isolated from
      humans and nine different animal species (cats, cattle, chickens, deer, dogs,
      ducks, horses, pigs, and sheep) were tested by a flip-plating technique.
      Approximately 38% of these strains were found to inhibit noncolicinogenic E. coli
      K12 strains. The percentage of potentially colicinogenic E. coli per animal
      species ranged from 14% for horse isolates to 64% for sheep strains. Those
      isolates that inhibited E. coli K12 were screened against E. coli O157:H7, and 42
      strains were found to be capable of inhibiting all 22 pathogenic strains tested.
      None of these 42 strains produced bacteriophages, and only 24 isolates inhibited
      serotype O157:H7 in liquid culture. The inhibitory activity of these strains was
      completely eliminated by treatment with proteinase K. When mixtures of these 24
      colicinogenic strains were grown in anaerobic continuous culture, the four-strain
      E. coli O157:H7 population was reduced at a rate of 0.25 log10 cells per ml per
      h, which was fivefold faster than the washout rate. Two strains originally
      isolated from cat feces (F16) and human feces (H30) were identified by repetitive
      sequences polymerase chain reaction as the predominant isolates in continuous
      cultures. The results of this work indicate that animal species other than cattle
      can be sources of anti-O157 colicinogenic strains, and these results also lead to
      the identification of at least two isolates that could potentially be used in
      preharvest control strategies.

PMID- 12233847
TI  - Suspending lettuce type influences recoverability and radiation sensitivity of
      Escherichia coli O157:H7.
AB  - An outbreak strain of Escherichia coli O157:H7 was inoculated onto closely
      related but structurally distinct types of lettuce (Lactuca sativa): Boston
      (butterhead lettuce), iceberg (crisphead lettuce), and green leaf and red leaf
      (colored variants of looseleaf lettuce). The E. coli O157:H7 was inoculated
      either onto the surface of cut leaf pieces or into a homogenized leaf suspension.
      Samples were gamma irradiated, and the radiation sensitivity of the inoculated
      bacteria was expressed as a D-value (the amount of ionizing radiation necessary
      to reduce the bacterial population by 90% [kGy]). The recovery of bacteria from
      nonirradiated leaf pieces was also measured. When inoculated onto the leaf
      surface, E. coli O157:H7 had significantly stronger radiation sensitivity on red
      leaf lettuce (D = 0.119 +/- 0.004 [standard error]) and green leaf lettuce (D =
      0.123 +/- 0.003) than on iceberg lettuce (D = 0.136 +/- 0.004) or Boston lettuce
      (D = 0.140 +/- 0.003). When E. coli O157:H7 was inoculated into a homogenized
      leaf suspension, its sensitivity was significantly stronger on iceberg lettuce (D
      = 0.092 +/- 0.002) than on green leaf lettuce (D = 0.326 +/- 0.012), Boston
      lettuce (D = 0.331 +/- 0.009), or red leaf lettuce (D = 0.339 +/- 0.010), with a
      threefold difference. Significantly fewer bacteria were recovered from the
      surface of iceberg lettuce than from the surfaces of the other types of lettuce
      examined. Following radiation doses of up to 0.5 kGy, the texture (maximum shear
      strength) of lettuce leaves was measured along the midrib and along the leaf edge
      for each type of lettuce. There was no meaningful change in texture for any type
      of lettuce for either leaf section examined at any dose up to 0.5 kGy. These data
      show (i) that relatively subtle differences between lettuce types can
      significantly influence the radiation sensitivity of associated pathogenic
      bacteria and (ii) that doses of up to 0.5 kGy do not soften lettuce leaves.

PMID- 12233848
TI  - Inactivation of acid-adapted and nonadapted Escherichia coli O157:H7 during
      drying and storage of beef jerky treated with different marinades.
AB  - The inactivation of both acid-adapted and unadapted Escherichia coli O157:H7
      during the processing of beef jerky was studied. Following inoculation with the
      pathogen, beef slices were subjected to different predrying marinade treatments,
      dried at 60 degrees C for 10 h, and stored at 25 degrees C for 60 d. The
      predrying treatments evaluated were as follows: (i) no treatment (C), (ii)
      traditional marinade (TM), (iii) double-strength TM modified with added 1.2%
      sodium lactate, 9% acetic acid, and 68% soy sauce with 5% ethanol (MM), (iv)
      dipping into 5% acetic acid for 10 min followed by application of TM (AATM), and
      (v) dipping into 1% Tween 20 for 15 min and then into 5% acetic acid for 10 min
      followed by TM (TWTM). Bacterial survivors were determined during drying and
      storage using tryptic soy agar with 0.1% pyruvate, modified eosin methylene blue
      agar, and sorbitol MacConkey agar. Results indicated that bacterial populations
      decreased during drying in the order of TWTM (4.9 to 6.7 log) > AATM > MM > C >
      or = TM (2.8 to 4.9 log) predrying treatments. Populations of acid-adapted E.
      coli O157:H7 decreased faster (P < 0.05) in AATM and TWTM than nonadapted cells
      during drying, whereas no significant difference was found in inactivation of
      acid-adapted and nonadapted inocula in C and TM samples. MM was more effective in
      inactivating the nonadapted than the adapted inoculum. Bacterial populations
      continued to decline during storage and dropped below the detection limit (-0.4
      log10 CFU/cm2) as early as day 0 (after drying) or as late as day 60, depending
      on acid adaptation, predrying treatment, and agar medium. The results indicated
      that acid adaptation may not increase resistance to the hurdles involved in jerky
      processing and that use of additional antimicrobial chemicals or preservatives in
      jerky marination may improve the effectiveness of drying in inactivating E. coli
      O157:H7.

PMID- 12233849
TI  - Irradiation temperature influences product quality factors of frozen vegetables
      and radiation sensitivity of inoculated Listeria monocytogenes.
AB  - Four frozen vegetables (broccoli, corn, lima beans, and peas) were gamma
      irradiated at subfreezing temperatures ranging from -5 to -20 degrees C to
      determine (i) the radiation sensitivity of an inoculated outbreak strain of
      Listeria monocytogenes (ATCC 49594), (ii) the effect of changing irradiation
      conditions (i.e., temperature) on that sensitivity, and (iii) the effect of the
      recommended radiation dose on the texture and color of irradiated frozen
      vegetables. The amounts of radiation necessary to reduce the bacterial population
      by 90% (D10-values) for L. monocytogenes differed significantly among vegetables
      at each irradiation temperature. D10 increased significantly with decreasing
      temperature for all vegetables, with each vegetable showing a different response
      pattern. At an irradiation temperature of -5 degrees C, D10 ranged from 0.505 kGy
      for broccoli to 0.613 kGy for corn. At -20 degrees C, D10 ranged from 0.767 kGy
      for lima beans to 0.916 kGy for peas. At -20 degrees C, radiation doses
      sufficient to achieve a 5-log10 kill (3.9 to 4.6 kGy) caused significant
      softening of peas and broccoli stems but not of corn or lima beans. Lower doses
      of comparable antimicrobial efficacy delivered at -5 degrees C (2.5 to 3.1 kGy)
      did not cause significant changes in texture in any vegetable. Color varied
      significantly among the dose-temperature combinations only for broccoli florets;
      this variation did not demonstrate a clear pattern of quality changes in response
      to irradiation.

PMID- 12233850
TI  - Control of Listeria monocytogenes on turkey frankfurters by generally-recognized
      as-safe preservatives.
AB  - Generally-recognized-as-safe chemicals applied to the surfaces of turkey
      frankfurters were evaluated for their ability to reduce populations of or inhibit
      the growth of Listeria monocytogenes. Frankfurters were treated prior to
      inoculation by dipping for 1 min in a solution of one of four preservatives
      (sodium benzoate, sodium propionate, potassium sorbate, and sodium diacetate) at
      three different concentrations (15, 20, and 25% [wt/vol]), with < 0.3% of the
      preservative being present for each frankfurter. Subsequently, 0.1 ml of a five
      strain mixture of L. monocytogenes (10(6) CFU/ml) was used to surface inoculate
      each frankfurter separately in a sterile stomacher bag. Inoculated frankfurter
      bags were held at 4, 13, and 22 degrees C, and L. monocytogenes cells were
      enumerated at 0, 3, 7, 10, and 14 days of storage. The results of this study
      revealed that at all three concentrations of all four preservatives, the initial
      populations of L. monocytogenes decreased immediately by 1 to 2 log10 CFU/g.
      After 14 days of storage at 4 degrees C, L. monocytogenes counts for all treated
      frankfurters were 3 to 4 log10 CFU/g less than those for the untreated
      frankfurters. After 14 days of storage at 13 degrees C, L. monocytogenes counts
      for frankfurters treated with 25% sodium benzoate or 25% sodium diacetate were
      3.5 to 4.5 log10 CFU/g less than those for untreated frankfurters, and those for
      frankfurters treated with 25% sodium propionate or 25% potassium sorbate were 2.5
      log10 CFU/g less than those for untreated frankfurters. In all instances, the
      degree of growth inhibition was directly proportional to the concentration of the
      preservative. Only frankfurters treated with 25% sodium diacetate or sodium
      benzoate were significantly inhibitory to L. monocytogenes when held at 22
      degrees C for 7 days or longer. Interestingly, the untreated frankfurters held at
      22 degrees C were spoiled within 7 days, with copious slime formation, whereas
      there was no evidence of slime on any treated frankfurters after 14 days of
      storage.

PMID- 12233851
TI  - Effect of organic acids and temperature on survival of Shigella flexneri in broth
      at pH 4.
AB  - The survival of bacterial pathogens in acidified foods depends not only on the
      hydrogen ion concentration, but also on the type of acid and the storage
      temperature. Shigella flexneri is a foodborne pathogen that is acid tolerant. The
      survival of S. flexneri 5348 in brain heart infusion broth supplemented with 0.04
      M acetic, citric, lactic, malic, or tartaric acid and adjusted to pH 4 with HCI
      or NaOH was studied. The control medium was brain heart infusion broth adjusted
      to pH 4 with HCI. Stationary-phase cells were inoculated into media at initial
      populations of 6 to 7 log10 CFU/ml and incubated at 4, 19, 28, and 37 degrees C.
      A two-phase linear inactivation model was applied to plate count data to derive
      lag times (tL) and slopes of the curves, from which D-values and time required
      for a 4-log10 decrease in population (T4D) were calculated. In all cases,
      survival increased with decreasing temperature. For each acid, tL, the D-value,
      and T4D increased with decreasing temperature. All acids inhibited S. flexneri to
      some extent but to differing degrees as follows: lactic acid, acetic acid >
      citric acid, malic acid, tartaric acid > HCl. The T4D values for the control
      medium and for media containing acetic, citric, lactic, malic, and tartaric acids
      were 64, 47, 50, 34, 58, and 52 h, respectively, at 37 degrees C and 2,607,
      1,498, 1,905, 1,346, 1,726, and 2,134 h, respectively, at 4 degrees C. The
      results of this study indicate that organic acids may aid in the inactivation of
      Shigella. However, these data also suggest that foods stored at or below room
      temperature containing low levels (< 1%) of acids could cause illness if
      contaminated with Shigella.

PMID- 12233852
TI  - Rapid determination of sanitizer concentration using impedance-based methods.
AB  - Chlorine, iodophor, and quaternary ammonium solutions of various concentrations
      were assayed with rapid test kits and with three Bactometer impedimetric test
      codes (the impedance, conductance, and capacitance test codes). An initial study
      was conducted to determine which test code was most suitable for each sanitizer.
      Impedance was shown to be the best for sodium hypochlorite solutions, conductance
      for iodophor solutions, and capacitance for quaternary ammonium solutions. When
      Bactometer results were compared with test kit results, linear regression
      revealed strong correlations for all three sanitizer solutions. For sodium
      hypochlorite concentrations of 0 to 100 ppm and 100 to 1,000 ppm, R2 values of
      0.87 and 0.99, respectively, were obtained. For iodophor concentrations between
      25 to 150 ppm, an R2 value of 0.95 was obtained. For quaternary ammonium compound
      concentrations of 100 to 1,000 ppm, an R2 value of 0.94 was obtained. The
      impedimetric methods proved to be simple and rapid (6 min) alternatives for
      measuring concentrations of the sanitizer solutions with a high level of
      certainty (P < 0.0002). The Bactometer will save time when multiple samples are
      tested.

PMID- 12233853
TI  - Effect of the licensing process on hygiene in retail butchers' premises in the
      West Midlands, United Kingdom.
AB  - As the result of a change in legislation, all retail butchers in England were
      required to be licensed by 1 November 2000. A fully implemented hazard analysis
      critical control point plan was a condition of the license. This longitudinal
      study assessed the effect of licensing on hygiene in a group of retail butchers
      in the West Midlands, England. A hygiene audit and environmental sampling were
      used to determine if the licensing process improved hygiene in the study group.
      At the end of the study, 30% of the original group were no longer trading as they
      had been, having either altered the product they were selling or ceased to trade.
      The remaining butchers showed a significant improvement in the hygiene of their
      premises, both in the audit scores and in the environmental sampling. The mean
      audit score for the group had improved from an initial score of 47.54 to 54.95 (P
      < 0.02). The contamination with Enterobacteriaceae on equipment used for cooked
      meat had also improved, decreasing from mean contamination levels of 1.38 log
      CFU/cm2 before licensing to mean contamination levels of -0.11 log CFU/cm2 after
      licensing (P < 0.00001).

PMID- 12233854
TI  - Detection of Alternaria fungal contamination in cereal grains by a polymerase
      chain reaction-based assay.
AB  - Alternaria sp. are important fungal contaminants of grain products; they secrete
      four structural classes of compounds that are toxic or carcinogenic to plants and
      animals and cause considerable economic losses to growers and the food-processing
      industry. Alternaria toxins have been detected by high-performance liquid
      chromatography (HPLC), enzyme-linked immunosorbent assay, and other techniques.
      Here, we report the development of a polymerase chain reaction (PCR)-based method
      for the detection of Alternaria DNA. PCR primers were designed to anneal to the
      ITS1 and ITS2 regions of the 5.8S rDNA gene of Alternaria alternata or Alternaria
      solani but not to other microbial or plant DNA. We compared the sensitivity of
      PCR in detecting Alternaria DNA, that of the HPLC method in detecting Alternaria
      alternariol and alternariol methyl ether toxins, and that of the morphological
      examination of mycelia and conidia in experimentally infested corn samples. The
      sensitivity of toxin detection for HPLC was above the level of contamination in a
      set of commercially obtained grain samples, resulting in negative scores for all
      samples, while the PCR-based method and mold growth plating followed by
      morphological identification of Alternaria gave parallel, positive results for 8
      of 10 samples. The PCR assay required just 8 h, enabling the rapid and
      simultaneous testing of many samples at a low cost. PCR-based evidence for the
      presence of Alternaria DNA followed by positive assay results for Alternaria
      toxins would support the rejection of a shipment of grain.

PMID- 12233855
TI  - Susceptibility of human rotavirus to ozone, high pressure, and pulsed electric
      field.
AB  - The rotavirus causes a food-transmitted gastroenteritis that affects mainly
      children. Currently, the food industry is interested in alternative food
      processing technologies, but research on the control of food-transmitted viruses
      by these technologies is limited. In this study, the human rotavirus was cultured
      on MA104 cells, and suspensions of the virus were prepared and treated with
      ozone, high pressure, and pulsed electric field (PEF). Virus viability was
      quantified as 50% tissue culture infectious doses (TCID50) per milliliter. Ozone
      at 25 microg/ml decreased rotavirus infectivity by 8 to 9 log10 TCID50/ml. High
      pressure was extremely effective against the rotavirus; treatment with 300 MPa
      for 2 min at 25 degrees C inactivated approximately 8 log10 TCID50/ml. A small
      fraction of the virus population, however, remained resistant to pressure
      treatments of up to 800 MPa for 10 min. Viruses surviving these extreme pressures
      showed a cytopathic effect different from that of the untreated viruses. The
      rotavirus was found to be resistant to PEF treatment at 20 to 29 kV/cm, for which
      no appreciable reductions in virus titer were observed.

PMID- 12233856
TI  - Rapid and simple estimation of microbiological quality of raw milk using
      chromogenic Limulus amoebocyte lysate endpoint assay.
AB  - A rapid chromogenic Limulus amoebocyte lysate (LAL) endpoint assay for the
      enumeration of total mesophilic microbial loads and coliforms was investigated as
      a means to assess the microbiological quality of raw milk. For experiment 1, raw
      milk samples (n = 25) were stored in a refrigerator (2 +/- 2 degrees C) and then
      analyzed at regular intervals (1, 5, 10, and 15 days). For experiment 2, fresh
      raw milk samples (n = 50) were tested to determine the utility of the LAL assay
      for fresh raw milk. The sample was diluted threefold in a 96-well microtiter
      plate with pyrogen-free water and assayed with a chromogenic LAL kit to find a
      final reaction point. The LAL results were compared with standard plate counts
      (SPC) and coliform counts determined by conventional plating methods. The results
      of the LAL assay were strongly correlated to conventional SPC (r2 = 0.93; n =
      100) and were highly correlated to coliforms (r2 = 0.74; n = 100). A highly
      significant linear relationship (r2 = 0.82; n = 50) was also observed between the
      predicted SPC based on the LAL value and the actual SPC. The results of LAL
      testing were classified into one of seven contamination groups. The data set for
      SPC was effectively differentiated using the LAL technique (P < 0.01). The
      chromogenic LAL assay was found to be a rapid (within 16 min) and simple (not
      requiring specific instruments) method for monitoring microbial levels in raw
      milk. This method may be successfully implemented to rapidly determine highly
      microbial contaminated raw milk (> 3.0 log10 CFU/ml of SPC).

PMID- 12233857
TI  - Evaluation of the 3M Petrifilm Enterobacteriaceae Count plate method for the
      enumeration of Enterobacteriaceae in foods.
AB  - Results of the 3M Petrifilm Enterobacteriaceae Count (EB) plate method were
      compared with those of the standard violet red bile glucose agar (VRBG) method
      for the detection and enumeration of Enterobacteriaceae. Studies involving 107
      bacterial strains demonstrated that the Petrifilm EB plate method is as sensitive
      as and more selective than the VRBG method. Sixty of the 62 pure
      Enterobacteriaceae cultures were recovered by both methods. In addition, 38 of
      the 45 non-Enterobacteriaceae organisms did not grow on the Petrifilm EB plate,
      while 28 of the 45 non-Enterobacteriaceae organisms did not grow on the VRBG
      plate. Colony counts from 174 naturally contaminated and 120 artificially
      inoculated dairy and nondairy food samples showed that the Petrifilm EB plate
      method performed as well as or better than the standard VRBG method for the
      enumeration of Enterobacteriaceae.

PMID- 12233858
TI  - Optimizing sporulation of Clostridium perfringens.
AB  - Many sporulation media have been developed for Clostridium perfringens, but none
      stimulates sporulation for all strains. The aim of our experiments was to develop
      a sporulation method using Duncan and Strong (DS) medium, which supports
      sporulation of a wide variety of strains. Different inoculation levels were
      tested, and the effects of sporulation-promoting substances and acid shock were
      evaluated. Furthermore, DS medium was compared with other sporulation media.
      Highest spore numbers in DS medium were obtained with a 10% 24-h fluid
      thioglycollate broth inoculum (5.0 x 10(5)/ml). Addition of theophylline and
      replacement of starch by raffinose increased spore yields for some strains, but
      most strains were not affected (average increases in log N/ml of 0.2 and 0.3,
      respectively). One strain was enhanced by the addition of bile, but other strains
      were strongly inhibited (average decrease in log N/ml of 2.5); agar did not
      influence sporulation. Neither short-time acid exposure nor addition of culture
      supernatant fluids of well-sporulating strains resulted in higher spore numbers
      in DS medium. None of the tested methods enhanced sporulation in general; only
      strain-dependent effects were obtained. Peptone bile theophylline medium was the
      most promising sporulation medium tested; peptone bile theophylline starch medium
      yielded highest spore numbers (2.5 x 10(5)/ml), but some strains failed to
      sporulate. In conclusion, adding theophylline to DS medium may optimize
      sporulation of C. perfringens, but peptone bile theophylline medium with or
      without starch is most suitable.

PMID- 12233859
TI  - Evaluation of antioxidative and mutagenic properties of 50% ethanolic extract
      from red beans fermented by Aspergillus oryzae.
AB  - Various bean products fermented by microorganisms are commonly consumed in Asian
      diets; however, the safety or functional properties of fermented beans can vary
      with different microbial species and with different processes being applied to
      different beans. The objectives of this study were to evaluate the antioxidative
      and mutagenic properties of 50% ethanolic extracts from red beans fermented by
      Aspergillus oryzae. The extracts' antioxidative activities, including
      alpha,alpha;-diphenyl-beta-picryl-hydrazyl (DPPH) radical-scavenging effects,
      Fe(2+)-chelating ability, and reducing power, were studied in vitro. The
      antioxidative effects provided by the extracts depended strongly on their
      concentrations. In general, antioxidative activity increased with extract
      concentration to a certain point and then leveled off as the concentration
      further increased. The fermented red bean extracts showed less of a scavenging
      effect on the DPPH radical and less reducing power than the commercial
      antioxidants alpha-tocopherol and butylated hydroxytoluene, but better Fe(2+)
      chelating ability. No mutagenicity or toxicity effect on any of the tested
      strains (Salmonella Typhimurium TA97, TA98, TA100, TA102, and TA1535) was found
      for the 50% ethanolic extracts of fermented red beans with the Ames mutagenicity
      assay. These results suggest that the 50% ethanolic extracts were not mutagenic.

PMID- 12233860
TI  - Detection of Listeria monocytogenes in pigs and pork.
AB  - In this study, we surveyed hogs (n = 300) as well as pork products (ground pork
      and raw chitterlings) for Listeria monocytogenes. Pig specimens collected before
      (tonsil swabs) and after slaughter (tonsils, lymph nodes, carcass swabs, and
      rectal contents) were examined for L. monocytogenes by enrichment with
      conventional enrichment broths followed by subculturing to selective agar. A
      multiplex polymerase chain reaction assay targeting the highly conserved 16S rRNA
      gene of the Listeria species as well as the hlyA gene unique to L. monocytogenes
      was used to screen aliquots of the enrichment (method I) as well as to confirm
      presumptive Listeria colonies from Columbia agar with 0.05% glucose supplemented
      with polymyxin B-acriflavine-lithium chloride-ceftazidime-aesculin-mannitol
      (PALCAM; method II). Subculturing to PALCAM agar was the more sensitive of the
      two methods on the basis of the overall detection of Listeria. For hog tissues,
      method I detected L. monocytogenes (0.87% positive) and no other Listeria spp. in
      all samples (n = 1,849). In contrast, method II detected significantly more (P <
      0.05) L. monocytogenes (2.38%) and Listeria spp. (0.38%) in these tissues. For
      small intestines (n = 300 raw chitterlings), L. monocytogenes was identified in
      8.3% of enrichments with University of Vermont modified Listeria enrichment
      broth; plating to PALCAM slightly improved recovery (9%). Overall, ground pork
      samples (n = 340) harbored L. monocytogenes (45% positive) and other Listeria
      species (1.5% positive), as determined by method I. Subculturing to PALCAM
      significantly (P < 0.05) improved the detection of L. monocytogenes (50.2%) but
      not that of other Listeria species (1.7%). L. monocytogenes isolates (n = 243)
      were assigned to serotype 1 (53.5%), serotype 4 (25%), and serotypes other than 1
      and 4 (21.4%).

PMID- 12233861
TI  - Salmonella spp. on chicken carcasses in processing plants in Poland.
AB  - Chickens at selected points in the slaughter process and after slaughter on the
      dressing line in poultry plants were sampled and analyzed for Salmonella. These
      chickens came from the northeast part of Poland. The examinations were carried
      out in quarters I, II, III, and IV of 1999. All the birds were determined to be
      healthy by a veterinary inspection. Swab samples were taken from the cloaca after
      stunning and from the skin surface and body cavity of the whole bird after
      evisceration, after rinsing at the final rinse station but before chilling in the
      spin-chiller, and after cooling in the continuous cooling plant at the end of the
      production day. In 1999, 400 whole chickens were examined. The percentage of
      these 400 chickens from which Salmonella spp. were isolated was relatively high
      (23.75%; Salmonella-positive results were observed in 95 cases). Salmonella spp.
      were found after stunning in 6% of the chickens (6 of 100 samples), after
      evisceration in 24% (24 of 100), before cooling in 52% (52 of 100), and after
      cooling in 13% (13 of 100). These results show that Salmonella spp. were found
      more often at some processing points than at others. The lowest Salmonella spp.
      contamination rate (6%) for slaughter birds was found after stunning, and the
      highest contamination rate was found before chilling (52%). The serological types
      of Salmonella spp. isolated from whole chickens were Salmonella Enteritidis,
      Salmonella Typhimurium, Salmonella Saintpaul, Salmonella Agona, and Salmonella
      Infantis. The results of these investigations indicate that Salmonella
      Enteritidis is the dominant serological type in infections of slaughter chickens,
      as it is in many countries.

PMID- 12233862
TI  - Use of pulsed ultraviolet laser light for the cold pasteurization of bovine milk.
AB  - Because of concerns that some potentially dangerous microorganisms may survive
      conventional heat pasteurization of milk and because the heat needed to sterilize
      milk affects marketability, the ability to efficiently cold pasteurized milk may
      become more desirable. In this pilot study, we investigated the use of pulsed
      ultraviolet (PUV) laser light to nonthermally (cold) pasteurized bovine milk.
      Dairy bulk tank milk was treated with UV light (248 nm) emitted from a pulsed
      excimer laser. The samples were then analyzed for surviving bacteria by spiral
      plate counting and subculturing in Trypticase soy broth. Other bulk tank milk
      samples were inoculated with one of eight relevant milk bacterial species before
      being exposed to laser light. There was no growth observed for any of the plated
      or subcultured samples exposed to 25 J/cm2. One bacterial isolate was then used
      to inoculate milk to further investigate bactericidal laser light doses. Growth
      was observed for samples treated with an average of 0.3 to 6.6 J/cm2 but not for
      those treated with 12.6 J/cm2. The results indicate that in principle, the
      bacterial content of milk can be adequately controlled by exposure to PUV laser
      light.

PMID- 12233863
TI  - Glufosinate-ammonium reduces growth and aflatoxin B1 production by Aspergillus
      flavus.
AB  - The herbicide glufosinate-ammonium (GA) [butanoic acid, 2-amino-4
      (hydroxymethylphosphinyl)-ammonium salt] was tested at concentrations from 2 to
      2,000 g GA per ml for activity against growth and aflatoxin B1 (AFB) production
      by the mycotoxigenic fungus Aspergillus flavus Link:Fr. The highest concentration
      (2,000 microg GA per ml) reduced colony diameter of A. flavus strain AF13 by 80%.
      AFB1 production was inhibited by 90% at this concentration. Reduction in mycelial
      dry weight and AFB1 production in response to GA application ranged from 17.2 to
      97.1% and from 39.1 to 90.1%, respectively. Of four concentrations tested, 2
      microg GA per ml was weakly inhibitory. In the kernel screening assay, AFB1
      production was inhibited 60 to 91% when kernels were preimmersed or immersed 5
      days after incubation in 200 microg GA per ml. Both concentrations (2 and 200
      microg GA per ml) reduced seed germination by 25 to 50%. Results indicate that GA
      has an inhibitory effect on growth and AFB1 production by A. flavus.

PMID- 12233864
TI  - Comparison of recovery of airborne microorganisms in a dairy cattle facility
      using selective agar and thin agar layer resuscitation media.
AB  - Thin agar layer (TAL) medium was developed at Kansas State University to improve
      the resuscitation of injured cells and has been shown to result in higher
      recovery than is obtained with selective media alone for cold-, heat-, salt-, and
      acid-injured cells. The experiment presented here was designed to determine the
      effectiveness of the TAL method for the recovery of possibly injured organisms
      from air. Eleven agar media were used for the experiment: tryptic soy agar (TSA),
      MacConkey sorbitol agar (MSA), TAL-MSA, Baird-Parker (BP) agar, TAL-BP agar,
      modified Oxford (MOX) agar, TAL-MOX agar, xylose lysine sodium desoxycholate
      (XLD) agar, TAL-XLD agar, Yersinia-selective (CIN) agar, and TAL-CIN agar. The
      TAL plates were prepared by pipetting 6 ml of selective agar into a BBL Rodac
      plate (65 by 15 mm). Selective agar was allowed to solidify, and then each plate
      was overlaid with 6 ml of TSA. Selective agar plates were prepared by pipetting
      12 ml of agar into BBL Rodac plates and allowing the agar to solidify. Samples
      were taken at an indoor cattle facility at five separate locations with a
      BioScience SAS air-sampling instrument. For each plate, 60 liters of air was
      sampled. Three replications of the experiment were performed. The TAL method
      resulted in higher counts of microorganisms on all media tested. In addition, 175
      isolates were selected randomly and identified in order to test the selectivity
      of TAL and the selective media for target organisms. The data obtained in this
      study show that the TAL resuscitation method is effective and necessary for the
      recovery of airborne organisms that may be injured.

PMID- 12233865
TI  - Monitoring of nitrite and N-nitrosamine levels in irradiated pork sausage.
AB  - Residual nitrite and N-nitrosamine levels were monitored on irradiated emulsion
      type cooked pork sausage in aerobic or vacuum packaging states during storage.
      The sausage was irradiated at 0, 5, 10, and 20 kGy and stored at 4 degrees C for
      4 weeks. The residual nitrite levels were significantly reduced by gamma
      irradiation (P < 0.05), whereas the vacuum packaging was more effective for
      nitrite reduction than aerobic packaging during storage. N-nitrosodimethylamine
      (NDMA) and N-nitrosopyrrolidine (NPYR) levels were significantly reduced in the
      vacuum packaged sausage irradiated with 20 kGy after 4 weeks. Reduction of NPYR
      in aerobically packaged sausage was also found after 4 weeks by irradiating with
      a 5-kGy or higher dose. NDMA reduction was shown in vacuum packaging and
      irradiation at 20 kGy. Gamma irradiation was effective in reducing the residual
      nitrite all throughout storage and N-nitrosamines in sausage after storage.

PMID- 12233866
TI  - Formation of biogenic amines in a typical semihard Italian cheese.
AB  - Given that the concentration of biogenic amines in cheeses depends on variety,
      age, and type of microflora, a study was undertaken to investigate the formation
      of these compounds during the ripening of a typical semihard Italian cheese.
      Tryptamine, phenylethylamine, putrescine, cadaverine, histamine, and tyramine
      contents were calculated in 30 samples of Montasio cheese characterized by
      different levels of proteolysis. Histamine and tyramine were the major amines.
      Tryptamine and phenylethylamine concentrations were very low at all ripening
      periods. Putrescine and cadaverine were present only in samples with anomalous
      fermentation processes. The relationship between the total amine content and the
      proteolytic maturation coefficient was calculated; however, even for higher
      levels of proteolysis, the biogenic amine content in Montasio cheese was below
      the level considered potentially toxic.

PMID- 12233867
TI  - Analytical methods for pesticide residue determination in bee products.
AB  - Monitoring pesticide residues in honey, wax, and bees helps to assess the
      potential risk of these products to consumer health and gives information on the
      pesticide treatments that have been used on the field crops surrounding the
      hives. The present review seeks to discuss the basic principles and recent
      developments in pesticide analysis in bee products and their application in
      monitoring programs. Consideration is given to extraction, cleanup,
      chromatographic separation, and detection techniques.

PMID- 12233868
TI  - Guidelines for the prevention of intravascular catheter-related infections.
      Centers for Disease Control and Prevention.
AB  - These guidelines have been developed for practitioners who insert catheters and
      for persons responsible for surveillance and control of infections in hospital,
      outpatient, and home health-care settings. This report was prepared by a working
      group comprising members from professional organizations representing the
      disciplines of critical care medicine, infectious diseases, health-care infection
      control, surgery anesthesiology interventional radiology pulmonary medicine,
      pediatric medicine, and nursing. The working group was led by the Society of
      Critical Care Medicine (SCCM), in collaboration with the Infectious Disease
      Society of America (IDSA), Society for Healthcare Epidemiology ofAmerica (SHEA),
      Surgical Infection Society (SIS), American College of Chest Physicians (ACCP),
      American Thoracic Society (ATS), American Society of Critical Care
      Anesthesiologists (ASCCA), Association for Professionals in Infection Control and
      Epidemiology (APIC), Infusion Nurses Society (INS), Oncology Nursing Society
      (ONS), Society of Cardiovascular and Interventional Radiology (SCVIR), American
      Academy of Pediatrics (AAP), and the Healthcare Infection Control Practices
      Advisory Committee (HICPAC) of the Centers for Disease Control and Prevention
      (CDC) and is intended to replace the Guideline for Prevention of Intravascular
      Device-Related Infections published in 1996 These guidelines are intended to
      provide evidence-based recommendations for preventing catheter-related
      infections. Major areas of emphasis include 1) educating and training health-care
      providers who insert and maintain catheters; 2) using maximal sterile barrier
      precautions during central venous catheter insertion; 3) using a 2% chlorhexidine
      preparation for skin antisepsis; 4) avoiding routine replacement of central
      venous catheters as a strategy to prevent infection; and 5) using
      antiseptic/antibiotic impregnated short-term central venous catheters if the rate
      of infection is high despite adherence to other strategies (i.e., education and
      training, maximal sterile barrier precautions, and 2% chlorhexidine for skin
      antisepsis). These guidelines also identify performance indicators that can be
      used locally by health-care institutions or organizations to monitor their
      success in implementing these evidence-based recommendations.

PMID- 12233869
TI  - Magnetic resonance imaging of articular cartilage: toward a redefinition of
      "primary" knee osteoarthritis and its progression.

PMID- 12233870
TI  - The challenges of estimating the national costs of osteoarthritis: are we making
      progress?

PMID- 12233871
TI  - Current consensus recommendations for rheumatoid arthritis therapy: a blind spot
      for osteoporosis prevention and treatment.

PMID- 12233872
TI  - First do no harm--a bone of contention in rheumatoid arthritis.

PMID- 12233873
TI  - HLA-DR/DQ haplotype in rheumatoid arthritis: novel allelic associations in UK
      Caucasians.
AB  - OBJECTIVE: To elucidate the relative importance of the HLA-DR and HLA-DQ loci in
      conferring genetic predisposition to rheumatoid arthritis (RA). METHODS: HLA-DRB1
      and HLA-DQB1 alleles were typed in a set of 685 patients with RA using sequence
      specific polymerase chain reaction. Allele and phenotype frequencies were
      compared with those in 2 large sets of historical, ethnically matched healthy
      controls, using the relative predispositional effect method. RESULTS: Positive
      association was confirmed with the shared epitope positive HLA-DRB1 alleles
      associated with RA in Caucasians. A significant susceptibility effect was
      observed with HLA-DRB1*09, described in other ethnically diverse populations but
      not in Caucasians. A significant underrepresentation of the HLA-DRB1*0103 variant
      was noted among the RA cases, supporting the proposed protective role of the
      DERAA motif at residues 70-74 of the DRbeta molecule. No HLA-DRB1 independent
      association of the HLA-DQB1 alleles, implicated in predisposing to RA, was
      evident. CONCLUSION: These data corroborate the shared epitope hypothesis of
      susceptibility to RA and provide strong evidence for the DRB1 locus as the
      primary RA susceptibility factor in the HLA region.

PMID- 12233874
TI  - Cytokine and chemokine mRNA produced in synovial tissue chronically infected with
      Chlamydia trachomatis and C. pneumoniae.
AB  - OBJECTIVE: We used a highly quantitative real-time reverse transcription
      polymerase chain reaction (RT-PCR) assay system to define the steady-state levels
      of mRNA encoding a large panel of soluble mediators of inflammation in synovial
      tissues from patients with chronic arthritis infected with Chlamydia trachomatis
      versus C. pneumoniae. METHODS: RNA/cDNA was prepared from synovial biopsies of 4
      patients with chronic arthritis and joint infection with C. trachomatis, 6 with
      C. pneumoniae at that site, 3 uninfected healthy controls, and 3 patients with
      undifferentiated oligoarthritis (UO) who were PCR negative for all organisms
      assayed. Real-time RT-PCR was used to assess relative mRNA levels from 12
      cytokine and 2 chemokine genes (IL-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-8, IL
      10, IL-12p35, IL-12p40, IL-15, IFN-gamma, TNF-alpha, MCP-1, RANTES). Input
      loading was normalized to 18S rRNA. Data were obtained for each mRNA from each
      sample in triplicate in comparison to the same mRNA level in the controls.
      RESULTS: In most C. trachomatis infected synovial tissue samples, high levels of
      IL-10 mRNA were present, with less mRNA for IL-8, IL-15, IFN-gamma, and TNF
      alpha. Synovial tissues from chronic arthritis patients with synovial C.
      pneumoniae showed significant levels of mRNA solely for IL-8 and IL-1beta. All
      other cytokine messengers assessed in each sample from each patient group were at
      or near control level. One patient with C. pneumoniae showed a high transcript
      level for RANTES, and one patient with C. trachomatis showed a high transcript
      level for MCP-1. No patient with UO showed elevated messenger level for any
      cytokines assayed, but RANTES mRNA was elevated in each. CONCLUSION: Our data
      suggest that while both C. trachomatis and C. pneumoniae have been associated
      with inflammatory joint disease, each elicits a somewhat different steady-state
      profile of mRNA encoding relevant cytokines and chemokines during chronic
      infection of synovial tissue. Precisely how these differing profiles relate to
      clinical aspects of synovial inflammation will require further study, but the
      observations confirm and extend data indicating potentially important differences
      in the pathobiology of these 2 bacterial species.

PMID- 12233875
TI  - Coexpression of microsomal prostaglandin E synthase with cyclooxygenase-2 in
      human rheumatoid synovial cells.
AB  - OBJECTIVE: Recently, microsomal prostaglandin (PG) E synthase (mPGES) was cloned
      as a terminal enzyme catalyzing PGH2 to PGE2. We investigated mPGES as well as
      cyclooxygenase (COX)-2, catalyzing arachidonic acid to PGH2, in synovial cells
      from patients with rheumatoid arthritis (RA). The effect of dexamethasone on
      mPGES expression was also studied. METHODS: Synovial cells were treated with
      interleukin 1beta (IL-1beta) and dexamethasone under various conditions, and
      expression of mPGES mRNA and protein was analyzed by Northern blot and Western
      blot, respectively. Conversions of arachidonic acid or PGH2 to PGE2 were measured
      by ELISA. Subcellular localization of mPGES and COX-2 was determined by
      immunofluorescent microscopic analysis. RESULTS: mPGES mRNA and protein
      expression were significantly upregulated by IL-1beta in synovial cells. COX-2
      mRNA and protein were also upregulated by IL-1beta, but with a different time
      course from that of mPGES. Conversion of PGH2 to PGE2 increased by IL-1beta and
      was correlated with mPGES expression. Increased conversion of arachidonic acid to
      PGE2 was maintained when mPGES and COX-2 were coexpressed. Subcellular
      localization of mPGES and COX-2 overlapped in the perinuclear region in IL-1beta
      stimulated synovial cells. Dexamethasone inhibited mRNA and protein expression
      for mPGES and increased conversion of arachidonic acid to PGE2, but inhibition of
      mPGES was weaker compared with that of COX-2 in IL-1beta stimulated cells.
      CONCLUSION: The results suggest that abundant PGE2 production at inflammation
      sites such as rheumatoid synovia is caused by the coordinated upregulation of
      mPGES and COX-2. Thus mPGES might be a potential new target for therapeutic
      strategies to control PGE2 synthesis specifically in patients with RA and other
      inflammatory diseases.

PMID- 12233876
TI  - Androgen receptors in human synoviocytes and androgen regulation of interleukin
      1beta (IL-1beta) induced IL-6 production: a link between hypoandrogenicity and
      rheumatoid arthritis?
AB  - OBJECTIVE: To investigate the hypothesis that synoviocytes possess androgen
      receptors (AR) that could be modulated by the non-aromatizable androgen,
      dihydrotestosterone (DHT), resulting in altered levels of inflammatory cytokines.
      METHODS: Using molecular analyses of AR in combination with the multiprobe
      ribonuclease protection assay and ELISA, we investigated the presence of AR and
      the effect of DHT on interleukin 1beta (IL-1beta) induced expression of the IL-6
      superfamily of cytokines in synoviocytes. RESULTS: Our studies corroborate the
      presence of AR in synoviocytes. DHT exerts a suppressive effect on IL-1beta
      induced IL-6, macrophage-colony stimulating factor (CSF), and granulocyte-CSF
      production by synoviocytes. This modulatory effect is exerted at both the
      transcriptional and translational level; 17beta-estradiol, at high
      concentrations, had a stimulatory effect. CONCLUSION: The identification of
      functional AR in synoviocytes and the modulatory effect of DHT on the
      inflammatory process in the joint suggest a direct link between hypoandrogenicity
      and rheumatoid arthritis (RA) disease status. Understanding the complex
      regulation of inflammatory cytokines by hormones may contribute to the
      development of new therapeutic targets for clinical intervention in RA.

PMID- 12233877
TI  - Tumor necrosis factor-alpha receptor II polymorphism in patients from southern
      Europe with mild-moderate and severe rheumatoid arthritis.
AB  - OBJECTIVE: To define the frequency of the exon 6 tumor necrosis factor-alpha (TNF
      alpha) receptor II (TNFRII) gene polymorphism in severe and mild-moderate
      rheumatoid arthritis (RA) and its possible influence on anti-TNF-alpha treatment
      responsiveness. METHODS: Two cohorts of patients with RA, the first (n = 97)
      defined as methotrexate responders (MTX-R) with mild-moderate synovitis, and the
      second (n = 78) defined as nonresponders to combination therapy and receiving
      anti-TNF-alpha treatment because of their severe and aggressive disease (TNF-T),
      were studied retrospectively and compared to age, sex, and ethnically matched
      controls (n = 84). In the prospective study, 66 patients with severe RA were
      followed over the first 6 months of anti-TNF-alpha therapy and their response was
      examined according to genotype. RESULTS: We observed a trend towards an increased
      frequency of the GG genotype in patients with severe RA (6.4%) in comparison with
      patients with mild-moderate disease (3.1%) and controls (1.2%). When looking at
      the response to anti-TNF-alpha therapy, we observed that after 12 weeks of
      treatment, 37.8% of the TT versus 10.7% of the TG/GG patients passed from high to
      medium-low disease activity (p = 0.03). CONCLUSION: In our cohorts of patients
      selected by response to the conventional therapy and by disease severity, our
      preliminary study results showed a trend towards a higher prevalence of the GG
      genotype for the exon 6 TNFRII polymorphism in the less responsive patients with
      more aggressive disease. We also found a lower degree of response to anti-TNF
      alpha treatments in patients carrying the G allele.

PMID- 12233878
TI  - The impact of functional status and change in functional status on mortality over
      18 years among persons with rheumatoid arthritis.
AB  - OBJECTIVE: To calculate mortality rate associated with rheumatoid arthritis (RA),
      to estimate the effect of initial functional status and of change in functional
      status on mortality among persons with RA, and to compare the mortality
      experience of such persons to that of the US population. METHODS: The study used
      a prospective panel of 1269 persons followed for a mean of 8.4 years (median 7
      yrs, interquartile range 3-12, maximum 18). Mortality status was ascertained from
      contacts with next of kin, study physicians, and search of the National Death
      Index. The Kaplan-Meier method was used to calculate the proportion dying in each
      time interval, with and without stratification for initial functional status
      [Health Assessment Questionnaire (HAQ) score] or average change in functional
      status. Cox proportional hazards regression was used to establish the effect of
      functional status, demographic characteristics, and health status on mortality
      risk. RESULTS: There were 270 deaths among the 1269 persons with RA. After 18
      years of followup the overall death rate was 39%. The death rates in the best
      through worst initial quartiles of HAQ score were 29, 33, 44, and 54%. The death
      rate was 51% among persons with declining HAQ score versus 31 and 32% among those
      with no change or improvement in this measure, respectively. Demographic and
      health status did not reduce the effect of HAQ or average change in HAQ on
      mortality risk. Compared to the US population, the persons with RA had a
      standardized mortality rate of 1.32. CONCLUSION: The persons with RA in this
      study had elevated mortality rates. Poor initial functional status and declining
      functional status significantly increased mortality risk among these persons with
      RA.

PMID- 12233879
TI  - Reduction of serum soluble CD26/dipeptidyl peptidase IV enzyme activity and its
      correlation with disease activity in systemic lupus erythematosus.
AB  - OBJECTIVE: CD26 is the cell surface activation antigen with dipeptidyl peptidase
      IV (DPPIV) enzyme activity at the extracellular domain that is preferentially
      expressed on memory T cells and has a role in T cell immune responses. The
      soluble form of CD26 is present in serum and recombinant soluble CD26 (rsCD26)
      can enhance in vitro antigen-specific T cell responses. To determine the role of
      soluble CD26 (sCD26) in the pathophysiology of patients with systemic lupus
      erythematosus (SLE), we measured levels of sCD26 and its specific DPPIV activity
      in serum. METHODS: Serum sCD26 levels and DPPIV activity were measured by
      sandwich ELISA in 53 patients with SLE and 54 healthy controls. Serum sCD26 was
      identified by immunoprecipitation and immunoblot analysis. Expression of CD26 on
      T cells was analyzed by flow cytometry. RESULTS: Serum levels of sCD26 and its
      specific DPPIV activity were significantly decreased in SLE and were inversely
      correlated with SLE disease activity index score, but not with clinical variables
      or clinical subsets of SLE. Close correlation between sCD26/DPPIV and disease
      activity was observed in the longitudinal study. CONCLUSION: Serum levels of
      sCD26 may be involved in the pathophysiology of SLE, and appear to be useful as a
      new disease activity measure for SLE.

PMID- 12233880
TI  - Increased prevalence of scleroderma in southwestern Ontario: a cluster analysis.
AB  - OBJECTIVE: To estimate the prevalence of scleroderma (systemic sclerosis, SSc) in
      3 cities, Windsor, Sarnia, and Woodstock, Ontario, within our referral area,
      which has a referral base population of 1 million. METHODS: To compare the
      addresses and exposures of referrals with SSc, we performed a case control study
      using our patients with scleroderma and 2 age and sex matched controls from the
      same rheumatologist's practice. RESULTS: Sixty-seven of 91 patients with SSc and
      87 of 154 controls responded. The mean age of patients with SSc was 53.2 years
      versus 52.8 years in controls. There was no statistically significant increase in
      the number of SSc patients from Windsor (population 197,694): 14 patients (15.4%)
      with SSc versus 18 controls (11.6%) (p < 0.41); or Sarnia (population 72,738): 7
      patients (7.7%) with SSc versus 7 controls (4.5%) (p < 0.31). However, there were
      9 cases (9.9%) from Woodstock (population 32,086) versus one control (0.64%) (p <
      0.0004). The point prevalence of scleroderma was at least 0.71/10,000 in Windsor,
      0.96/10,000 in Sarnia, and 2.8/10,000 in Woodstock. There were no significant
      between-group differences in exposure to industrial toxins or chemicals including
      vinyl chloride, silica, and benzene, but exposure rates in both groups were low.
      Occupations and proportion of those who were work disabled were not different.
      Patients with SSc were not more likely to have smoked cigarettes (p < 0.43);
      however, they were more likely to drink at least 6 drinks of alcohol per week (p
      < 0.04) and had more dental fillings (p < 0.05). Patients with SSc knew on
      average 3.2 others with this disease, and controls knew only 0.25 others with
      scleroderma (p < 0.00001). Two patients with SSc knew someone with SSc in their
      workplace versus none of the controls. CONCLUSION: Our a priori expected higher
      prevalence of scleroderma in Windsor and Sarnia did not reach significance, but
      the cluster in Woodstock seems statistically validated, and the exact reason for
      this cluster remains unclear. It is unlikely that all patients with SSc in
      Woodstock were seen by us, so the prevalence of scleroderma is at least
      2.8/10,000, which is a medium to high prevalence compared to other studies.
      Associations with alcohol and dental fillings require further study.

PMID- 12233881
TI  - Interleukin 10 (IL-10) influences autoimmune response in primary Sjogren's
      syndrome and is linked to IL-10 gene polymorphism.
AB  - OBJECTIVE: To investigate the association between serum levels of interleukin 10
      (IL-10), the synthesis of autoantibodies, salivary gland disease activity,
      clinical manifestations, and IL-10 microsatellite polymorphism in patients with
      primary Sjogren's syndrome (pSS). METHODS: Serum IL-10 and autoantibody levels
      [IgG anti-Ro and anti-La, total and IgA rheumatoid factor (RF)] were measured by
      ELISA. A minor salivary gland (MSG) biopsy was performed in all patients and the
      focus score was determined as a measure of salivary gland disease activity. In
      addition, IL-10 microsatellite typing was performed by polymerase chain reaction
      technique. RESULTS: IL-10 concentration was higher in patients (n = 39) than in
      controls (n = 15) (21.4 +/- 6.7 vs 2.5 +/- 3.5 pg/ml; p = 0.001). We found a
      significant positive correlation between IL-10 levels and titers of IgA RF, anti
      Ro, and anti-La antibodies, as well as focus score. In comparison with patients
      with low IL-10 production (< 9.5 pg/ml), patients producing high IL-10 had
      significantly more episodes of cutaneous vasculitis and a higher proportion of
      them carried the IL-10.G9 allele. CONCLUSION: Autoimmune response in pSS patients
      as well as salivary gland disease activity and cutaneous involvement appears to
      be mediated by IL-10 levels; in turn, there is a linkage with IL-10 gene
      polymorphism.

PMID- 12233882
TI  - Expression of hepatocyte growth factor and its receptor (c-met) in skin
      fibroblasts from patients with systemic sclerosis.
AB  - OBJECTIVE: To determine the effect of excessive induction of hepatocyte growth
      factor (HGF)/c-met signaling in fibroblasts derived from patients with systemic
      sclerosis (SSc). METHODS: Fibroblasts were obtained from skin of patients with
      SSc and healthy controls. The 2.4 kb interleukin 1alpha (IL-1alpha) cDNA was
      subcloned into pcDNA3 expression vector, which was stably transfected into normal
      fibroblasts by lipofection. HGF production in cultured fibroblasts was measured
      by ELISA. C-met protein (a receptor for HGF) in cultured fibroblasts was
      evaluated by immunocytochemistry using polyclonal anti-c-met antibody. Production
      of procollagen type I was estimated by an ELISA system using antibodies against
      procollagen type I C-peptide. RESULTS: Cultured skin fibroblasts expressed mRNA
      and protein of HGF constitutively in both SSc and control cultures. However, HGF
      production in SSc fibroblasts was significantly higher than in normal
      fibroblasts. In both SSc and normal fibroblasts, HGF production was dose
      dependently increased by the addition of recombinant IL-1alpha.
      Immunocytochemical staining revealed that c-met was spontaneously expressed in
      SSc fibroblasts, whereas no expression of c-met was detected in normal
      fibroblasts. C-met mRNA was expressed in normal fibroblasts transfected with the
      IL-1alpha gene. Addition of recombinant HGF (100 ng/ml) to cultured SSc
      fibroblasts significantly decreased procollagen type I production. CONCLUSION:
      High concentration of HGF inhibited collagen production in cultured fibroblasts
      derived from patients with SSc. Overexpression of HGF/c-met appears to be a
      biological feedback response to the fibrotic process of SSc, suggesting that the
      antifibrotic effect of HGF might be used as a novel strategy for treatment of
      SSc.

PMID- 12233883
TI  - Possible function of salivary gland epithelial cells as nonprofessional antigen
      presenting cells in the development of Sjogren's syndrome.
AB  - OBJECTIVE: To explore the potential of salivary gland epithelial cells to act as
      nonprofessional antigen-presenting cells (APC) in the development of Sjogren's
      syndrome (SS). METHODS: Expression of HLA-DR antigens, costimulatory molecules,
      and adhesion molecules on epithelial cells was immunohistochemically examined in
      labial salivary glands from patients with SS. An association with the expression
      of T cell derived cytokine messenger RNA (mRNA) was observed. The expression of
      these molecules was confirmed using cultured salivary gland epithelial cells. The
      ability of the salivary gland epithelial cells as nonprofessional APC was
      examined in a mixed culture system using the salivary gland epithelial cells and
      allogeneic lymphocytes. RESULTS: Expression of HLA-DR antigens, CD80,
      intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule
      (VCAM), and E-selectin was immunohistochemically detected on duct cells from all
      patients; however, the expression of CD86 was limited to only some patients.
      Concomitant expression of CD80 on duct cells and Th1 cytokine mRNA, and CD86 on
      duct cells and Th2 cytokine mRNA, was observed. Interferon-gamma (IFN-gamma)
      induced the cultured salivary gland epithelial cells to express HLA class I
      antigens, HLA-DR antigens, CD80, and ICAM-1, while tumor necrosis factor-alpha
      (TNF-alpha) induced the expression of HLA class I antigens, CD80, CD86, and VCAM.
      Cultured salivary gland epithelial cells treated with either IFN-gamma or TNF
      alpha also caused allogeneic lymphocytes to proliferate. CONCLUSION: The ability
      of salivary gland epithelial cells to express HLA-DR antigens, costimulatory
      molecules, and adhesion molecules and thus to act as nonprofessional APC was
      suggested. CD80 and CD86 expression of these cells was also suggested to be
      involved in the activation of Th1 and Th2, respectively.

PMID- 12233884
TI  - Magnetic resonance imaging criteria for distinguishing between inclusion body
      myositis and polymyositis.
AB  - OBJECTIVE: To develop diagnostic imaging criteria for polymyositis (PM) and
      sporadic inclusion body myositis (sIBM). METHODS: We investigated 220 patients
      with suspected inflammatory myopathies by magnetic resonance imaging (MRI).
      Findings were compared with the results of clinical and biological examinations
      and muscle biopsy. PM and IBM were diagnosed in 25 patients each. Quantitative
      and qualitative MRI analysis of the 3 muscle groups of the 2 thighs included
      fatty infiltration, atrophy, inflammation, and the type and distribution of the
      lesions. RESULTS: MRI was abnormal in all patients. Fatty infiltration and
      atrophy were more frequent in patients with sIBM (p < 0.05). Inflammation as the
      sole abnormality was preferentially encountered in PM (p = 0.05). Widespread
      abnormalities were more frequent in sIBM (p < 0.01). Abnormalities in PM tended
      to be distributed along the fascia. Involvement of the anterior group, an
      asymmetrical distribution, and a distal predominance were all more frequent in
      sIBM (p < 0.001). CONCLUSION: Despite some overlap in MRI findings between the 2
      diseases, MRI was useful for distinguishing PM from sIBM.

PMID- 12233885
TI  - Modified anti-CD3 therapy in psoriatic arthritis: a phase I/II clinical trial.
AB  - OBJECTIVE: Treatment of autoimmune diseases with therapies that tolerize
      pathogenic lymphocytes may obviate the need for longterm global
      immunosuppression. In vitro, non-Fc receptor binding derivatives of anti-murine
      CD3 monoclonal antibodies tolerize type 1 T cells and stimulate type 2 T cells.
      Recently, a humanized non-FcR binding derivative of the anti-human CD3 Mab OKT3,
      huOKT3gamma1(ala-ala), has been described. We hypothesized that this Mab may be
      safe and efficacious in the treatment of type 1 T lymphocyte mediated chronic
      autoimmune diseases such as psoriatic arthritis (PsA). METHODS: In a Phase I/II
      trial, 7 patients with PsA were treated with escalating daily doses of
      huOKT3gamma1(ala-ala) for 12 to 14 days. Number of tender and swollen joints and
      a visual analog pain scale were used to rate disease activity at entry and Day 30
      and Day 90 after treatment. RESULTS: At Day 30, 6 of 7 patients had > or = 75%
      improvement in the number of inflamed joints and an average 63% improvement on
      the patient pain scale. Two of 6 responders had sustained improvement at Day 90.
      No patient treated with an initial dose < or = 1 mg had significant side effects,
      nor did they have detectable increases in serum cytokines. One patient treated
      with 4 mg without escalation developed mild cytokine release symptoms associated
      with elevation of interleukin 10. Transient T cell depletion occurred following
      treatment with the maximum dose of 4 mg, which resolved by Day 30. Antiidiotypic
      antibodies developed in 2 patients; however, there was no concurrent decrease in
      efficacy. CONCLUSION: These data indicate that huOKT3gamma1(ala-ala) may be
      useful in treating PsA.

PMID- 12233887
TI  - Muscle derived, cell based ex vivo gene therapy for treatment of full thickness
      articular cartilage defects.
AB  - OBJECTIVE: To evaluate the effectiveness of transplanted allogeneic muscle
      derived cells (MDC) embedded in collagen gels for the treatment of full thickness
      articular cartilage defects, to compare the results to those from chondrocyte
      transplantation, and to evaluate the feasibility of MDC based ex vivo gene
      therapy for cartilage repair. METHODS: Rabbit MDC and chondrocytes were
      transduced with a retrovirus encoding for the beta-galactosidase gene (LacZ). The
      cells were embedded in type I collagen gels, and the cell proliferation and
      transgene expression were investigated in vitro. In vivo, collagen gels
      containing transduced cells were grafted to the experimental full thickness
      osteochondral defects. The repaired tissues were evaluated histologically and
      histochemically, and collagen typing of the tissue was performed. RESULTS: The
      MDC and chondrocyte cell numbers at 4 weeks of culture were 305 +/- 25% and 199
      +/- 25% of the initial cell number, respectively. The initial percentages of LacZ
      positive cells in the MDC and chondrocyte groups were 95.4 +/- 1.9% and 93.4 +/-
      3.4%, and after 4 weeks of culture they were 84.2 +/- 3.9% and 76.9 +/- 4.3%,
      respectively. In vivo, although grafted cells were found in the defects only up
      to 4 weeks after transplantation, the repaired tissues in the MDC and chondrocyte
      groups were similarly better histologically than control groups. Repaired tissues
      in the MDC group were mainly composed of type II collagen, as in the chondrocyte
      group. CONCLUSION: Allogeneic MDC could be used for full thickness articular
      cartilage repair as both a gene delivery vehicle and a cell source for tissue
      repair.

PMID- 12233886
TI  - The T cell receptor repertoire in psoriatic synovitis is restricted and T
      lymphocytes expressing the same TCR are present in joint and skin lesions.
AB  - OBJECTIVE: To investigate the T cell receptor (TCR) repertoire in psoriatic
      synovitis and to determine whether T lymphocytes in joint and skin lesions show
      the same Vbeta CDR3 region. METHODS: The expression of Valpha and Vbeta families
      was evaluated by reverse transcriptase-polymerase chain reaction. The CDR3 region
      of some Vbeta families was analyzed by cloning and sequencing. RESULTS: We found
      a diverse variable beta chain usage within psoriatic synovial fluid of 11
      patients although some Valpha and Vbeta families were more frequently expressed
      without evidence of clonality. Analysis of TCR in skin and synovial lesions of 3
      patients showed identical CDR3 sequences, indicating that T cells bearing the
      same TCR are present at the 2 sites of chronic inflammation. CONCLUSION: These
      data suggest that common or similar crossreactive antigens present in the 2
      locations are responsible for the expansion of the same TCR-bearing T cells
      possibly already activated by a superantigen. This supports the hypothesis that
      both polyclonal and oligoclonal lymphocyte activation contribute to the
      initiation and persistence of psoriatic arthritis.

PMID- 12233888
TI  - Challenges of estimating health service utilization for osteoarthritis patients
      on a population level.
AB  - OBJECTIVE: To examine how estimates of osteoarthritis (OA) related health service
      utilization and medical care charges vary based on how the population of patients
      is defined, we compared a large cohort of patients identified through an
      administrative OA diagnosis relative to a subgroup of patients in whom this
      diagnosis had been validated through medical record review. METHODS: We
      identified all members (> or = 18 years of age) of a Massachusetts group model
      health maintenance organization (HMO) with documentation of at least one health
      care encounter associated with an OA diagnosis during the period 1994-96 (n =
      10,740). From this population we randomly selected 700 subjects. Trained nurse
      reviewers abstracted relevant clinical, laboratory, and radiologic data from
      their medical records. Physician reviewers evaluated the abstracted information
      and rated the evidence for the presence of OA according to 3 levels (definite,
      possible, and unlikely). All persons rated by the physician reviewers as having
      definite OA were included in the validated subgroup (n = 442). Health service
      utilization and medical care charges were assessed in all persons with an
      administrative OA diagnosis who were not randomly sampled (n = 10,040) and the
      validated subgroup (n = 442) across the following domains: (1) ambulatory
      encounters associated with an OA diagnosis, (2) relevant radiographic studies,
      (3) relevant surgical procedures, and (4) relevant medication use. RESULTS: Those
      in the validated subgroup had higher rates of ambulatory OA associated health
      care encounters, radiographic studies, surgical procedures, and analgesic and/or
      antiinflammatory medication dispensings. Patients in the validated subgroup were
      significantly more likely to be in the highest quartile for total one year
      charges for the care of OA. CONCLUSION: Estimates of health service utilization
      are substantially higher for populations of patients in whom a diagnosis of OA
      has been validated through medical record review, as compared with unvalidated
      populations identified solely through diagnoses contained in administrative
      records. Thus using health service utilization estimates based on an unvalidated
      sample may lead to an inaccurate estimate when extrapolated to the overall
      population of patients with OA.

PMID- 12233891
TI  - The inflammatory process in the mechanism of decreased serum uric acid
      concentrations during acute gouty arthritis.
AB  - OBJECTIVE: To clarify the mechanism of decreased serum uric acid (SUA)
      concentrations during acute gouty arthritis. METHODS: Data from patients with
      acute gouty arthritis during and after an attack were investigated
      retrospectively. Other investigations, including changes in urinary excretion and
      biochemical markers, were performed prospectively. RESULTS: SUA was significantly
      lower in the acute phase (7.5 +/- 1.4 mg/dl) than in the intercritical phase (8.5
      +/- 0.9 mg/dl) (p < 0.0001). During the acute gout phase, a normal SUA level was
      found in 20 of 41 patients (49%). C-reactive protein (CRP) during acute attacks
      was significantly correlated with plasma interleukin 6 (IL-6) and cortisol (r =
      0.645, p < 0.005; r = 0.460, p < 0.05). Percentage change in SUA at onset of
      attack correlated with CRP and IL-6 (r = 0.762, p < 0.0001; r = 0.630, p <
      0.005), as well as with increased urinary excretion of uric acid, estimated by
      percentage change in fractional excretion of uric acid (FEua) during attack (r =
      0.447, p < 0.05). Further, change in FEua was correlated with plasma cortisol
      levels during the acute attack (r = 0.534, p < 0.05). CONCLUSION: Decrease in SUA
      during acute gouty arthritis is associated with increased urinary excretion of
      uric acid; an inflammatory process may play a role in the mechanism.

PMID- 12233890
TI  - Uricase formulated with polyethylene glycol (uricase-PEG 20): biochemical
      rationale and preclinical studies.
AB  - OBJECTIVE: Humans have a non-sense codon inserted into the 5 prime end of the
      open reading frame of urate oxidase, and thus express an enzymatically inactive
      fragment of this enzyme; and consequently are unable to metabolize uric acid into
      allantoin and are prone to develop hyperuricemia and gout. Various urate oxidases
      (uricase) from mammals and microorganisms have been administered to humans with
      hyperuricemia and gout. Although successful in lowering plasma uric acid, these
      therapies have had limited application due to undesirable biochemical properties
      of the enzymes used, the short circulating half-life, and inherent antigenicity
      of these preparations. METHODS: We compared urate oxidase from a variety of
      sources for specific enzyme activity, pH optimum, affinity, and retention of
      enzyme activity under physiological conditions. A variety of polyethylene glycols
      (PEG) were tested to formulate uricase. RESULTS: Urate oxidase from Candida
      utilis had more favorable enzymatic properties and PEG of 20,000 MW (termed
      uricase-PEG 20) had greatly reduced antigenicity and increased circulating half
      life as compared to those previously described. CONCLUSION: It is anticipated
      that uricase-PEG 20 may have utility as a treatment for hyperuricemia and gout.

PMID- 12233892
TI  - Rate of knee cartilage loss after partial meniscectomy.
AB  - OBJECTIVE: Surgical removal of the meniscus of the knee is thought to be a risk
      factor for later appearance of knee osteoarthritis (OA). We examined whether
      there is a difference in cartilage loss in those who undergo a partial
      meniscectomy compared to healthy controls. METHODS: Eight patients who underwent
      a meniscectomy (5 partial medial, 3 partial lateral) and 13 controls with normal
      knee radiographs and magnetic resonance imaging (MRI) had an MRI at baseline and
      at a mean 28.6 +/- 7.6 months followup. Articular cartilage volumes were
      determined by processing images acquired in the sagittal plane using T1 weighted
      fat saturation MRI on an independent work station. RESULTS: The mean +/- SD of
      percentage rates of cartilage loss from baseline volume were 4.1 +/- 2.8% per
      year for the meniscectomy subjects and -2.3 +/- 3.0% per year for the controls
      (difference 6.5% per year, 95% CI 3.7-9.3% per year; p < 0.001). After adjustment
      for age, body mass index, and sex the difference increased slightly to 6.9% per
      year (95% CI 3.4-10.3%; p = 0.001). CONCLUSION: This study suggests that
      significant rates of cartilage loss are seen in subjects post partial
      meniscectomy compared with healthy controls. This may be a useful model in which
      to examine therapies to prevent OA.

PMID- 12233889
TI  - A simple method of selecting gout patients for treatment with uricosuric agents,
      using spot urine and blood samples.
AB  - OBJECTIVE: To develop a simple means of selecting gout patients for treatment
      with uricosuric agents. METHODS: In 124 gout patients, spot urine and blood were
      sampled before breakfast and after overnight fast (except water) on the day of 24
      h urine collection. Spot urine uric acid/creatinine ratio (Ua/Cr mmol/mmol) and
      serum creatinine x Ua/Cr (Scr*Ua/Cr micromol/l) were calculated together with 24
      h urinary uric acid excretion/body surface (24 Ua/S). The patients were then
      classified either below or above 2.84 mmol/m2/day for 24 Ua/S. RESULTS:
      Classifications based on spot urine Ua/Cr (cut off value set at 0.34), spot urine
      Scr*Ua/Cr (cut off value set at 28.1), and a combination of spot urine Ua/Cr and
      Scr*Ua/Cr were found to be not significantly different in diagnostic accuracy for
      the detection of patients with 24 Ua/S below 2.84 mmol/m2 (77%, 81%, and 81%,
      respectively) and sensitivity (80%, 83%, and 76%, respectively). However,
      specificity by a combination of spot urine Ua/Cr, and spot urine Scr*Ua/Cr was
      higher than by spot urine Ua/Cr alone (91% vs 74%, P < 0.05), although the
      specificity was not significantly different between a combination and spot urine
      Scr*Ua/Cr alone (91% vs 78%) or between spot urine Ua/Cr and spot urine Scr*Ua/Cr
      (74% vs 78%). CONCLUSION: A combination of spot urine Ua/Cr and spot urine
      Scr*Ua/Cr may be clinically useful in selecting gout patients with 24 Ua/S below
      2.84 mmol/m2 for treatment with uricosuric agents without adverse effects.

PMID- 12233893
TI  - Heel spur formation and the subcalcaneal enthesis of the plantar fascia.
AB  - OBJECTIVE: To describe the structure and significance of subcalcaneal heel spurs
      associated with the plantar fascia. METHODS: The enthesis of the plantar fascia
      was removed from 17 elderly cadavers by sagittal saw cuts either side of the
      medial tuberosity, radiographs were taken, and the tissue was processed for
      routine histology. Sagittal sections were stained with toluidine blue, Masson's
      trichrome, or alcian blue, and sections were matched with the corresponding
      radiographs. RESULTS: Spurs develop on the deep surface of the plantar fascia but
      their formation is heralded by degenerative changes that occur within it.
      According to differences between small and large spurs, we propose that there are
      3 stages in their development: (1) an initial formation of cartilage cell
      clusters and fissures at the plantar fascia enthesis; (2) thickening of the
      subchondral bone plate at the enthesis as small spurs form; (3) development of
      vertically oriented trabeculae buttressing the proximal end of larger spurs. The
      spurs grow by a combination of intramembranous and chondroidal ossification.
      CONCLUSION: Contrary to popular belief, subcalcaneal heel spurs cannot be
      traction spurs as they do not develop within the plantar fascia itself. They are
      thus fundamentally different from heel spurs in the Achilles tendon. We suggest
      instead that they develop as a consequence of degenerative changes that occur in
      the plantar fascia enthesis.

PMID- 12233894
TI  - 14 day endoscopy study comparing risedronate and alendronate in postmenopausal
      women stratified by Helicobacter pylori status.
AB  - OBJECTIVE: Bisphosphonates are effective treatment for osteoporosis but have been
      associated with gastrointestinal (GI) mucosal injury. This study compared the
      incidence of gastric ulcers after treatment with risedronate, a pyridinyl
      bisphosphonate, or alendronate, a primary amino bisphosphonate, in healthy
      postmenopausal women stratified by Helicobacter pylori status. METHODS: Subjects
      were randomized to receive risedronate 5 mg (n = 318) or alendronate 10 mg (n =
      317) daily for 14 days. Endoscopy and evaluator-blind assessments of the
      esophageal, gastric, and duodenal mucosa were performed at baseline and on Days 8
      and 15. RESULTS: Overall, gastric ulcers > or = 3 mm were observed in 18 (6.0%)
      of 300 evaluable subjects in the risedronate group and 36 (12.1%) of 297 in the
      alendronate group during treatment (p = 0.013). On Day 8, the incidences of
      gastric ulcers in the risedronate and alendronate groups were 3.6% and 6.6%,
      respectively (p = 0.133), and on Day 15, they were 3.3% and 8.7% (p = 0.008). The
      incidence of gastric ulcers was not affected by H. pylori status. Mean gastric
      endoscopy scores at Days 8 and 15 were significantly lower in the risedronate
      group than in the alendronate group (p < 0.001). Mean esophageal and duodenal
      endoscopy scores were similar in the 2 groups at Days 8 and 15. When the
      treatment groups were combined, gastric endoscopy scores were significantly
      higher among H. pylori negative than H. pylori positive subjects at Days 8 and 15
      (p < 0.05). Upper GI adverse events were reported by 18 (5.7%) subjects in the
      risedronate group (19 events) and 28 (8.8%) subjects in the alendronate group (32
      events). Symptoms did not predict the presence of mucosal damage. CONCLUSION:
      Risedronate was associated with a significantly lower incidence of gastric ulcers
      than alendronate. H. pylori infection did not increase the incidence of
      bisphosphonate related gastric ulcers. The findings from this 14 day study in
      healthy volunteers support the hypothesis that bisphosphonates may differ from
      one another in their potential to produce upper GI mucosal damage.

PMID- 12233895
TI  - Influence of Helicobacter pylori eradication therapy on the occurrence of
      gastrointestinal events in patients treated with conventional nonsteroidal
      antiinflammatory drugs combined with omeprazole.
AB  - OBJECTIVE: To evaluate the effect of eradication treatment of Helicobacter pylori
      and the influence of H. pylori status on the incidence of gastrointestinal (GI)
      events in rheumatic patients receiving longterm conventional nonsteroidal
      antiinflammatory drug (NSAID) therapy combined with omeprazole. METHODS: Patients
      (n = 919) requiring longterm NSAID therapy entered this multicenter, open label,
      parallel group study. H. pylori positive patients were randomized to receive
      either eradication therapy (omeprazole 20 mg bid, amoxicillin 1 g bid, and
      clarithromycin 500 mg bid for 7 days) or no therapy. Both these groups and the H.
      pylori negative patients were given omeprazole, 20 mg once daily, along with
      NSAID for the study duration (5-8 weeks). Treatment failure (primary outcome
      variable) was defined as the occurrence of severe GI event (symptomatic ulcer,
      bleeding, perforation) or dyspepsia leading to discontinuation of NSAID therapy,
      unscheduled consultation, or upper GI tract endoscopy. RESULTS: Treatment failure
      was recorded in 9/294 (3.06%) infected patients receiving eradication therapy,
      8/219 (3.65%) infected patients receiving omeprazole alone, and 5/391 (1.28%) H.
      pylori negative patients (p > 0.05). H. pylori eradication did not appear to
      influence the incidence and severity of dyspeptic symptoms in infected patients.
      CONCLUSION: Our results do not support the use of H. pylori eradication therapy
      in rheumatic patients receiving conventional NSAID along with omeprazole.

PMID- 12233896
TI  - Prevalence of arthritis: analysis of data from the US Behavioral Risk Factor
      Surveillance System, 1996-99.
AB  - OBJECTIVE: Arthritis and other rheumatic conditions are a large and growing
      public health problem and constitute the most frequent cause of disability in the
      United States. Because many people with arthritis do not see a doctor for it,
      this study uses community surveys to estimate the prevalence of arthritis among
      adults and to identify subgroups with high prevalence rates of arthritis.
      METHODS: We used data from a cross sectional random digit telephone survey (the
      Behavioral Risk Factor Surveillance System) of noninstitutionalized adults aged
      18 years or older conducted from 1996 through 1999. Estimates of self-reported
      arthritis, defined as chronic joint symptoms or doctor diagnosed arthritis, were
      derived from data in 15 states and Puerto Rico, all of which used an optional
      arthritis survey module for one or more years from 1996 through 1999. RESULTS:
      After adjusting for age, we found that arthritis was more common among several
      groups not recognized consistently in previous studies to have high prevalence
      rates of arthritis: separated and divorced people, those out of work or unable to
      work, and current and former smokers. It was also more common among several
      previously recognized groups with high prevalence rates of arthritis: older
      people, women, people with low education, people with low household incomes,
      physically inactive people, and overweight and obese people. CONCLUSION: Because
      appropriate management can minimize the influence of arthritis, health care
      providers should ask patients in high risk groups about arthritis symptoms. In
      addition, clinical and public health interventions may be targeted toward those
      subgroups with high prevalence rates of arthritis to reduce the disability from
      arthritis and improve their health related quality of life.

PMID- 12233897
TI  - Disease course and outcome of juvenile rheumatoid arthritis in a multicenter
      cohort.
AB  - OBJECTIVE: To determine the disease course and outcome in a multicenter cohort of
      patients with juvenile rheumatoid arthritis (JRA). METHODS: All patients with JRA
      seen at 3 pediatric rheumatology centers were identified from databases and/or
      clinic records. Inclusion criteria were a diagnosis of JRA (1977 American College
      of Rheumatology criteria), a followup period of at least 5 years since onset, and
      a minimum age of 8 years. Patients were examined and completed a Childhood Health
      Assessment Questionnaire (CHAQ). Kaplan-Meier curves were constructed to estimate
      rates of remission, relapse, and arthroplasty. Remission was defined as absence
      of active arthritis while off treatment for at least 2 years. Outcome measures
      were active disease duration, CHAQ scores, pain determined by visual analog
      scales, physician's global assessments, and Steinbrocker functional
      classifications. Years of education and employment status were ascertained.
      RESULTS: We studied 392 patients of 652 (60%) who met the selection criteria. The
      probabilities of remission at 10 years after onset were 37, 47, 23, and 6% for
      patients with systemic, pauciarticular, RF- polyarticular, and RF+ polyarticular
      JRA, respectively. The probability of relapse varied from 30 to 100% at 15 years.
      The probability of arthroplasty varied from 13 to 57% after 15 years of active
      disease. We found 2.5% of patients assessed were in Steinbrocker Classes III or
      IV and 6% were in the highest CHAQ score (> 1.5) group. Compared with national
      statistics, fewer female patients received post-secondary education and
      unemployment rates for patients 20 to 24 years of age were higher. CONCLUSION:
      Our results indicate that JRA is a disease that often extends into adulthood.
      Compared to previous decades, functional outcome has improved; however, the
      estimated rate of arthroplasty remains very high. Patients with JRA may have
      difficulty entering the workforce.

PMID- 12233898
TI  - Gonadal function in male adolescents and young males with juvenile onset systemic
      lupus erythematosus.
AB  - OBJECTIVE: To evaluate gonadal function in male adolescents and young men with
      juvenile onset systemic lupus erythematosus (SLE). METHODS: Four young men with
      SLE underwent clinical and laboratory evaluation, testicular ultrasound, follicle
      stimulating hormone, luteinizing hormone, prolactin, testosterone, and anti-sperm
      antibody determination. The semen analyses were performed according to the WHO
      guidelines and Kruger strict criteria. All patients were asked to provide 3 semen
      samples over a period of 2 months. A new sample was collected 6 months later.
      RESULTS: The median disease duration was 6.6 years. The median age at initial
      ejaculation was 13.5 years. All 4 patients had severe disease with renal
      involvement (WHO class IV or V). The SLICC/ACR damage index at the time of study
      entry ranged between 0 and 3. The patients' Tanner stage was P5G5; all reported
      normal erection and libido. Gonadal evaluation by thorough examination of the
      genitalia and ultrasound was normal. Anti-sperm antibodies were negative in all
      patients. Only one patient showed high FSH and LH levels. The initial and final
      semen evaluations of the 4 patients were abnormal (azoospermia,
      oligoastenoteratospermia, or teratospermia). One patient was receiving
      azathioprine and 2 were receiving cyclophosphamide at the time of study entry.
      CONCLUSION: Although these patients had normal sexual activity and normal
      external genitalia, their fertility was decreased based on the sperm
      abnormalities. Serial semen analyses in larger study populations will be
      necessary to clarify the degree and duration of sperm abnormalities in male
      patients with SLE in general.

PMID- 12233899
TI  - Treatment of catastrophic antiphospholipid syndrome with defibrotide, a proposed
      vascular endothelial cell modulator.
AB  - OBJECTIVE: To define at the molecular level the vascular endothelial cell (VEC)
      injury characteristics of catastrophic antiphospholipid syndrome (CAPS) and to
      report successful therapeutic use of a VEC modulator, defibrotide. METHODS: We
      describe a 55-year-old man with primary APS with an intractable prothrombotic
      state (CAPS) resistant to combined therapy with heparin, warfarin, aspirin, and
      dipyridamole. Treatment with defibrotide was conducted in the context of an
      investigational phase II protocol where the dose was regulated and individualized
      by disease/patient-specific molecular and clinical markers. RESULTS: The patient
      entered complete remission with defibrotide treatment. During treatment, dose
      dependent pharmacological actions of defibrotide and key stress markers for VEC
      injury were identified. Evidence of defibrotide's polypharmacology included
      downregulation of cytokines, notably tumor necrosis factor-alpha, as the earliest
      effect, cellular differentiation of VEC, possibly with direct regulatory effect
      over cellular genes, and the reversal of platelet consumption and prothrombotic
      state. Von Willebrand antigen levels were used as the sole marker to guide
      therapy. CONCLUSION: This case demonstrates effective remission of CAPS with
      defibrotide treatment. In contrast to theories that CAPS is triggered by ischemic
      and thrombotic tissue damage, these data present VEC injury as the primary and
      representative lesion of CAPS. The pathogenesis may involve concurrent impairment
      of different VEC functions. Achieving remission may require a polypharmacologic
      approach, represented here by use of defibrotide.

PMID- 12233900
TI  - Massive splenomegaly and hypersplenism in a young woman with primary Sjogren's
      syndrome.

PMID- 12233901
TI  - A mosaic of cells in a patient with systemic lupus erythematosus.

PMID- 12233902
TI  - Arthroscopy and psoriatic knee joint synovitis.

PMID- 12233903
TI  - In quest of the Holy Grail: efficacy versus effectiveness in rheumatoid
      arthritis.

PMID- 12233904
TI  - SAPHO syndrome and transient hemiparesis in a child: coincidence or new
      association?

PMID- 12233905
TI  - CA15-3 and cancer associated serum antigen assays are alternatives to the KL-6
      assay for measuring serum MUC-1 levels in patients with interstitial lung disease
      associated with polymyositis/dermatomyositis.

PMID- 12233907
TI  - Antiinflammatory effect of simvastatin in patients with rheumatoid arthritis.

PMID- 12233906
TI  - Cerebral embolism complicating Libman-Sacks endocarditis--full recovery using
      recombinant tissue plasminogen activator.

PMID- 12233908
TI  - West Nile virus activity--United States, July 31-August 7, 2002, and Louisiana,
      January 1-August 7, 2002.
AB  - This report summarizes West Nile virus (WNV) surveillance data reported to CDC
      through ArboNET and by states and other jurisdictions as of August 7, 2002.

PMID- 12233909
TI  - Outbreak of Salmonella serotype Javiana infections--Orlando, Florida, June 2002.
AB  - On July 16, 2002, the Minnesota Department of Health identified two cases of
      Salmonella serotype Javiana infections among persons who had attended the 2002
      U.S. Transplant Games held at theme park A in Orlando, Florida, during June 25
      29. Isolates from both patients were indistinguishable by pulsed field gel
      electrophoresis (PFGE). The U.S. Transplant Games is a 4-day athletic competition
      among recipients of solid organ transplants (i.e., heart, liver, kidney, lung,
      and pancreas) and bone marrow transplants. Approximately 6,000 persons from the
      United States and five other countries, including 1,500 transplant-recipient
      athletes, participated in the games. This report summarizes the results of an
      ongoing epidemiologic and laboratory investigation that has identified 141 ill
      persons in 32 states who attended the games.

PMID- 12233910
TI  - Childhood lead poisoning associated with tamarind candy and folk remedies-
      California, 1999-2000.
AB  - Lead poisoning affects children adversely worldwide. In the United States,
      elevated blood lead levels (BLLs) (>10 microg/dL) result primarily from exposure
      to lead-based paint or from associated lead-contaminated dust and soil; however,
      other sources of lead exposure, including folk remedies, Mexican terra cotta
      pottery, and certain imported candies, also have been associated with elevated
      BLLs in children. This report describes five cases in California of lead
      poisoning from atypical sources. Health-care providers should be aware of the
      potential hazards of certain food products, and community members should be
      educated about potential sources of lead poisoning for children.

PMID- 12233911
TI  - Human rabies--California, 2002.
AB  - On March 31, 2002, a man aged 28 years residing in Glenn County, California, died
      from rabies encephalitis caused by a rabies virus variant associated with the
      Mexican free-tailed bat (Tadarida brasiliensis) (Figure). This report summarizes
      the investigation by the Glenn County Health Department (GCHD) and the California
      Department of Health Services (CDHS). Persons who observe abnormal behavior in
      any wildlife species should contact animal control or animal rescue agencies
      immediately and should avoid approaching or handling these animals.

PMID- 12233912
TI  - Outbreak of tularemia among commercially distributed prairie dogs, 2002.
AB  - Tularemia has been identified recently as the cause of a die-off in captured wild
      prairie dogs (Cynomys ludovicianus) (Figure) at a commercial exotic animal
      distributor in Texas. The Texas Department of Health and CDC immediately notified
      all state health departments and are investigating the outbreak.

PMID- 12233913
TI  - Multidetector row CT: principles and clinical applications.
AB  - Multidetector row CT (MDCT) is the latest advancement in CT technology. The use
      of multiple detector rows allows faster scanning and thinner collimation. These
      improvements allow routine scans to be performed faster with higher z-axis
      resolution. New applications can also be developed using this new technology. To
      fully appreciate the potential of these new MDCT scanners, it is important for
      the radiologist to be familiar with the scanner design and capabilities. This
      article reviews the basic principles of MDCT scanners. Scanner/detector design,
      beam collimation/slice thickness, radiation dose, data manipulation, and display
      are discussed.

PMID- 12233914
TI  - How we do it: pulmonary embolism.

PMID- 12233915
TI  - Case of the month. Gastric Cancer.

PMID- 12233916
TI  - Three-dimensional CT angiography with multidetector CT data: study optimization,
      protocol design, and clinical applications in the abdomen.
AB  - The quality and flexibility of abdominal CT angiograms have been well served by
      advances in multidetector technology and volume rendering techniques, which allow
      real-time, interactive modification of high-quality data sets. We have applied
      this approach to many of the established and developing roles of CT and we
      discuss and illustrate protocol design and application.

PMID- 12233917
TI  - Bacon on business: advice from an Elizabethan sage to 21st century medical
      leaders.

PMID- 12233918
TI  - Does consumption of cola beverages cause bone fractures in children?

PMID- 12233919
TI  - George Palade--Nobel Laureate for discoveries in cell biology.

PMID- 12233920
TI  - Direct current cardioversion of atrial fibrillation--the next 40 years.

PMID- 12233921
TI  - Safety of electrical cardioversion in patients with atrial fibrillation.
AB  - OBJECTIVES: To determine the incidence of thromboembolic complications after
      electively performed electrical cardioversion in patients with atrial
      fibrillation and to assess the clinical variables associated with an increased
      risk of thromboembolism after cardioversion. PATIENTS AND METHODS: This is a
      retrospective analysis of 834 successful electrical cardioversions performed in
      717 patients from 1990 through 1994. Outcome measures included embolic
      complications at 1-month follow-up after cardioversion and logistic regression
      models to measure the associations among clinical, anticoagulation, and
      thromboembolic events and to identify independent predictors of these events.
      RESULTS: The rate of embolic events after cardioversion was low (0.9%; 95%
      confidence interval, 0.4%-1.8%). Patients with a therapeutic international
      normalized ratio had no embolic events. Adequate anticoagulation was
      independently associated with reduced risk of thromboembolism. Hypertension and
      diabetes mellitus were independently associated with increased risk of
      embolization. CONCLUSION: Adequate anticoagulation reduced the risk of
      embolization after cardioversion. Diabetes mellitus and hypertension are
      independently associated with increased risk of embolization early after
      cardioversion.

PMID- 12233922
TI  - Absence of Kaposi sarcoma among Ethiopian immigrants to Israel despite high
      seroprevalence of human herpesvirus 8.
AB  - OBJECTIVE: To determine the prevalence of Kaposi sarcoma (KS) and human
      herpesvirus 8 (HHV-8) seropositivity in Ethiopian Jewish immigrants to Israel.
      METHODS: A Western blot assay was used to determine the seroprevalence of HHV-8
      in serum samples from 202 randomly selected human immunodeficiency virus (HIV)
      negative and 47 HIV-positive Ethiopian immigrants; samples were obtained on
      arrival of the immigrants in Israel. The Israel Cancer Registry provided
      comprehensive data on the occurrence of KS among Ethiopian immigrants and in the
      non-Ethiopian population of Israel. RESULTS: A total of 39.1% and 57% of the HIV
      negative and HIV-positive Ethiopians, respectively, were infected with HHV-8
      (P<.03). However, none of the Ethiopians examined and none of the other HIV
      negative Ethiopians among about 45,000 immigrants had KS. Moreover, only 1
      (0.85%) of 118 Ethiopian patients with acquired immunodeficiency syndrome (AIDS)
      developed KS compared with 49 (12.5%) of 391 non-Ethiopian AIDS patients
      (P<.001). CONCLUSION: Although HHV-8 infection is common in Ethiopian Jewish
      immigrants to Israel, these patients almost never develop KS, in marked contrast
      to the strong association usually observed. The mechanism behind this
      population's unique protection requires further study.

PMID- 12233923
TI  - Incidence of seizures in patients with multiple sclerosis: a population-based
      study.
AB  - OBJECTIVE: To determine whether multiple sclerosis (MS) is associated with
      occurrence of seizure activity. PATIENTS AND METHODS: The medical records of all
      incidence patients with MS in Olmsted County, Minnesota, from 1935 to 1991 were
      reviewed. The incidence of seizures was calculated by using 3 methods: including
      only seizures that occurred after definite diagnosis of MS, including all
      seizures occurring after onset of the first symptoms of MS, and including any
      seizures regardless of the time of onset relative to MS. These incidences were
      age-adjusted to the 1970 US population and then compared with the age-adjusted
      incidence rate of seizures in the general population of Olmsted County. RESULTS:
      The age-adjusted incidence of seizures among MS patients was not significantly
      higher than the age-adjusted incidence of seizures in the general population of
      Olmsted County. The age-adjusted incidence of first unprovoked seizures in
      Rochester, Minn, was 61 per 100,000 person-years. In patients with the definite
      diagnosis of MS, the age-adjusted Incidence was calculated at 61 per 100,000
      person-years (95% confidence interval [CI], 7-114). In the group with seizures
      after onset of symptoms, the age-adjusted incidence rate was 80 per 100,000
      person-years (95% CI, 24-135). In the group with seizures at any time in their
      life, the age-adjusted incidence rate was 82 per 100,000 person-years (95% CI, 41
      158). CONCLUSION: The present study does not suggest that occurrence of seizures
      is more common in MS patients than in the general population.

PMID- 12233924
TI  - Determination of potential adjuvant systemic therapy benefits for patients with
      resected cutaneous melanomas.
AB  - OBJECTIVE: To facilitate both better physician understanding of prognostic
      information (baseline and with adjuvant interferon) for individual patients who
      present with resectable melanomas and more informed patient decisions about
      whether they should receive adjuvant high-dose interferon therapy after resection
      of primary melanomas. PATIENTS AND METHODS: Baseline survival estimates were
      derived from a surgical database composed of 17,600 patients with complete
      clinical, pathologic, and follow-up data. Potential survival benefits ascribed to
      adjuvant interferon were obtained from results of a meta-analysis of Eastern
      Cooperative Oncology Group studies, which provided evidence for a uniform
      relative benefit of high-dose interferon across different baseline risk groups. A
      mathematical formula was then applied to these data to allow for individual
      prognostic information. RESULTS: The 5-year survival benefits in patients who
      received high-dose interferon after surgery, using the assumptions of the
      provided prognoses and interferon survival improvements, ranged up to 13%.
      CONCLUSIONS: These data should allow for a better understanding of baseline
      prognosis in individual patients and a better understanding of the potential
      benefits of adjuvant interferon. They should also help patients make more
      informed decisions regarding their treatment options.

PMID- 12233925
TI  - Medical services utilization and prognosis in Parkinson disease: a population
      based study.
AB  - OBJECTIVES: To investigate prognostic outcomes and utilization of medical
      services by patients with Parkinson disease (PD) and to identify predictors of
      such use. PATIENTS AND METHODS: Using the medical records linkage system of the
      Rochester Epidemiology Project, we identified an incidence cohort of 89 PD cases
      (Olmsted County, Minnesota, 1979-1988) and a reference group of 89 subjects
      without PD of the same age and sex and from the same population. Both patients
      with PD and reference subjects were followed up historically by medical record
      review from onset of PD (or index year) through death, last contact with the
      system, or end of study. RESULTS: Patients with PD had significantly more
      physician consultations per year (median, 7.9 vs 5.9; P=.001) and more emergency
      department visits per year (median, 0.6 vs 0.4; P=.05) than did reference
      subjects. Response to dopaminergic medications and higher education predicted
      more physician consultations among patients. The PD patients used neuroleptics
      and antidepressants significantly more frequently than reference subjects. The
      risk of nursing home placement was significantly increased for PD patients
      compared with reference subjects (relative risk, 6.7; 95% confidence interval,
      3.7-12.1; P<.001). Poor response to dopaminergic medications, lower education
      level, older age at onset of PD, and dementia predicted a shorter time between
      onset and nursing home placement among PD patients. Survival was significantly
      reduced in PD patients compared with reference subjects (relative risk, 2.2; 95%
      confidence interval, 1.4-3.4; P<.001). Good response to dopaminergic medications,
      higher education, younger age at onset of PD, and absence of dementia predicted
      better survival among PD patients. CONCLUSIONS: Patients with PD used outpatient
      and nursing home services more often than subjects without PD. Patients with PD
      also experienced a reduced survival time. Demographic and clinical
      characteristics influenced utilization patterns and outcomes.

PMID- 12233926
TI  - Primer on medical genomics. Part III: Microarray experiments and data analysis.
AB  - Genomics has been defined as the comprehensive study of whole sets of genes, gene
      products, and their interactions as opposed to the study of single genes or
      proteins. Microarray technology is one of many novel tools that are allowing
      global and high-throughput analysis of genes and gene products. In addition to an
      introduction on underlying principles, the current review focuses on the use of
      both complementary DNA and oligodeoxynucleotide microarrays in gene expression
      analysis. Genome-wide experiments generate a massive amount of data points that
      require systematic methods of analysis to extract biologically useful
      information. Accordingly, the current educational communication discusses
      different methods of data analysis, including supervised and unsupervised
      clustering algorithms. Illustrative clinical examples show clinical applications,
      including (1) identification of candidate genes or pathological pathways (ie,
      elucidation of pathogenesis); (2) identification of "new" molecular classes of
      diseases that may be relevant in disease reclassification, prognostication, and
      treatment selection (ie, class discovery); and (3) use of expression profiles of
      known disease classes to predict diagnosis and classification of unknown samples
      (ie, class prediction). The current review should serve as an introduction to the
      subject for clinician investigators, physicians and medical scientists in
      training, practicing clinicians, and other students of medicine.

PMID- 12233927
TI  - Virology, pathogenetic mechanisms, and associated diseases of Kaposi sarcoma
      associated herpesvirus (human herpesvirus 8).
AB  - Kaposi sarcoma-associated herpesvirus (KSHV) is a recently discovered and
      characterized member of the herpesvirus family. It is one of a few viruses proved
      to be associated with tumorigenesis in humans. Its causal association with 4
      clinical and epidemiologic variants of Kaposi sarcoma (classic, endemic,
      iatrogenic, and acquired immunodeficiency virus-associated) as well as with
      several lymphoproliferative disorders (notably primary effusion lymphoma and
      multicentric Castleman disease) is reviewed critically. Issues related to the
      epidemiology, transmission, and molecular and serologic diagnosis are discussed.
      Several intriguing oncogenic mechanisms of KSHV infection have been identified.
      These are often dependent on the interaction of KSHV with other viruses, such as
      human immunodeficiency virus, Epstein-Barr virus, or both. However, important
      problems remain and once resolved will substantially enhance our understanding of
      oncogenesis in general and viral-induced oncogenesis in particular. This may also
      translate into improved treatment and perhaps prevention of this common and
      intriguing viral infection.

PMID- 12233928
TI  - Colonoscopy as a screening test for colorectal cancer in average-risk
      individuals.
AB  - Screening for colorectal cancer has become the standard of care and is currently
      recommended by most major health organizations, including the American Cancer
      Society. Randomized controlled trials using fecal occult blood testing as the
      screening strategy have shown a reduction in mortality due to colorectal cancer.
      However, colorectal cancer differs from other cancers in that a variety of
      screening tests have been approved and recommended by experts. The advantages and
      disadvantages of different screening tests have been the subject of intense
      debate. Colonoscopy has theoretical advantages over other screening tests,
      including direct visualization of the entire colon and, more importantly, removal
      of precancerous adenomatous lesions. This review discusses the advantages and
      disadvantages of colonoscopy as a screening test for colorectal cancer with
      regard to efficacy, cost-effectiveness, and patient compliance.

PMID- 12233929
TI  - Human immunodeficiency virus: the initial physician-patient encounter.
AB  - Human immunodeficiency virus (HIV) infection is increasingly becoming a disease
      managed by HIV specialists. However, all primary care physicians have an
      important role that can affect the epidemic in the United States. These
      physicians must be able to appropriately identify patients at risk, screen for
      and diagnose HIV, provide counsel, and refer those who are infected to
      specialists. The primary care physician will often continue to provide medical
      care in collaboration with an HIV specialist. The patient will receive optimal
      care when the primary care physician is knowledgeable regarding HIV and the
      evaluation of the newly diagnosed patient. Through appropriate screening,
      evaluation, diagnosis, and counseling, the primary care physician will not only
      improve the care of the individual patient but also potentially decrease the
      spread of HIV. This article answers some of the questions that primary care
      physicians are likely to have when evaluating an adult with newly diagnosed HIV
      infection.

PMID- 12233930
TI  - Images and reflections from Mayo Clinic heritage.

PMID- 12233931
TI  - 65-year-old woman with painful leg ulcers.

PMID- 12233932
TI  - Multiple cardiovascular complications in a patient with relapsing polychondritis.
AB  - Relapsing polychondritis is an uncommon disease of unknown etiology, usually
      manifested by inflammatory changes of cartilaginous tissues. Cardiovascular
      complications are rare but have been associated with adverse prognosis. Aortitis,
      vasculitis of large- and medium-sized arteries with aneurysm formation,
      valvulitis, pericarditis, and atrioventricular conduction disturbances have been
      reported as late complications of relapsing polychondritis. We describe a 42-year
      old man who developed all the known cardiovascular complications of relapsing
      polychondritis except for clinically evident pericarditis. This case illustrates
      the multiple, varied, and potentially fatal cardiovascular complications that can
      occur with this disorder. Patients with relapsing polychondritis should be
      monitored closely for development of such complications.

PMID- 12233933
TI  - Demystifying seizures and epilepsy: introduction to the symposium on seizures.

PMID- 12233934
TI  - Characteristics of the epilepsies.
AB  - Epilepsy is not a specific disease but rather a heterogeneous group of disorders
      that have in common the characteristic of recurrent, usually unprovoked seizures.
      Epileptic seizures represent the intermittent and self-limited clinical
      manifestations (signs and symptoms) that result from abnormally excessive and
      synchronous activity of neurons. Seizures are categorized as partial (with the
      initial activation of a limited number of neurons in a part of 1 hemisphere) or
      generalized (with the initial activation of neurons throughout both hemispheres).
      Epilepsy, however, is more than just recurrent seizures. It includes a specific
      etiology, associated neurologic abnormalities, a genetic background,
      environmental factors, responses to various therapies, and other factors. The
      disability and the effect on quality of life may be different for each
      individual. A variety of epileptic conditions have associated clinical and
      electroencephalographic (EEG) features that can be categorized as syndromes. Many
      of the syndromes have different etiologies in different patients yet share common
      characteristics such as the age at seizure onset; seizure type(s); intellectual
      development; and findings on neurologic examinations, EEGs, and neuroimaging. The
      epilepsies are categorized into 3 groups (idiopathic, cryptogenic, and
      symptomatic) on the basis of the presumed etiologies. Understanding the
      characteristics of the epilepsy syndromes provides a powerful tool for the
      prognosis and treatment of individuals experiencing seizures. In this article, we
      discuss characteristic features of the epilepsies.

PMID- 12233935
TI  - Role and limitations of routine and ambulatory scalp electroencephalography in
      diagnosing and managing seizures.
AB  - The scalp electroencephalogram (EEG) is the cornerstone in the diagnosis and
      treatment of seizure disorders. The EEG, with its excellent temporal resolution,
      provides a direct measurement of cortical electrophysiology, revealing, for
      example, the presence of interictal epileptiform discharges that identify regions
      of an epileptogenic brain. We define the EEG characteristics of focal and
      generalized epileptiform discharges and provide evidence for their varying
      diagnostic importance in different patient populations. Identification of
      nonepileptiform EEG transients, such as wicket waves, small sharp spikes,rhythmic
      temporal theta activity, and 14- and 6-Hz positive bursts, that can be confused
      for epileptiform transients is emphasized. A final point is that the clinician
      must interpret EEG findings within the overall clinical context.

PMID- 12233936
TI  - Cognitive development in school-age children with vertically transmitted HIV
      infection.
AB  - We examined a broad range of neuropsychological functioning in school-age
      children with vertically transmitted HIV infection and a control group made up of
      siblings of children with HIV infection. Fourteen children with HIV (2
      asymptomatic, 8 mildly symptomatic, and 4 with AIDS) and 11 control children were
      administered a battery of neuropsychological tests assessing intelligence,
      receptive language, expressive language, visual and verbal memory, visual-motor
      speed and coordination, visual-motor and visual-spatial processing, fine motor
      skill, and academic achievement. Results revealed that school-age children with
      vertically transmitted HIV infection show many areas of cognitive function within
      the normal range. Despite normal cognitive development, subtle motor impairments
      were documented in children with vertically transmitted HIV infection. Our
      results are the first report of fine motor and motor strength deficits in school
      age children with vertically transmitted HIV. Lastly, computed tomography (CT)
      results suggest that children with HIV who have documented structural anomalies
      in the brain may be at risk for deficits in visual-motor and visual-spatial
      processing. This finding should be explored with larger samples and other
      measures to determine its generalizability.

PMID- 12233937
TI  - Tower of London test performance in children with poor arithmetic skills.
AB  - The Tower of London (TOL) has been used to assess executive functions in both
      children and adults with documented brain dysfunction. Like many other measures
      of executive function, it has not been widely used in the assessment of learning
      disabilities in children. However, if performance on the TOL discriminated among
      groups of children with different academic strengths and weaknesses, then it may
      be useful in identifying learning disability subtypes. The purpose of this study
      was to determine whether performance on the TOL would differ among 3 groups of
      children: those with arithmetic difficulties, those with reading difficulties,
      and those with no academic difficulties. The group with arithmetic difficulties
      exhibited significantly greater impairment on the TOL than either the group with
      reading difficulties or the group with no difficulties. The latter 2 groups
      performed similarly. The clinical utility of the TOL, as well as the relation
      between arithmetic deficits and executive functions, are discussed.

PMID- 12233938
TI  - Are planning, working memory, and inhibition associated with individual
      differences in preschool ADHD symptoms?
AB  - The association between executive function (EF; planning, working memory, and
      inhibition) and individual differences in symptoms of attention deficit
      hyperactivity disorder (ADHD) was explored in a sample of preschool children. One
      hundred sixty children (between the ages of 3 years, 0 months and 5 years, 6
      months), selected so as to oversample high ADHD scorers, performed 3 tasks
      previously shown to measure planning (Tower of London), working memory (Noisy
      Book) and inhibition ("Puppet Says..."). EF measures were reliable (kappa > .77)
      and were correlated with IQ (rs > .38) and age (rs > .59). Once IQ and age were
      controlled, planning and working memory (r = .41) were correlated. Planning and
      working memory were not correlated with inhibition (rs < .20). There was no
      association between ADHD and working memory or planning (rs < .12). There was a
      significant negative association between ADHD and conduct problems and inhibition
      (r = -.30 and r = -.25, respectively). Only the link with ADHD persisted after
      the effects of other factors were controlled for in a multiple regression.
      Specific deficits in inhibitory control rather than general EF deficits are
      associated with ADHD in the preschool period. This association is linear in
      nature, supporting the idea that ADHD is better seen as a continuum rather than a
      discrete category. This association provides evidence for Barkley's (1997) view
      that ADHD is underpinned by inhibitory deficits in the preschool period.

PMID- 12233939
TI  - Spatial cognition in young children with spinal muscular atrophy.
AB  - Success in visuospatial tasks has often been demonstrated in teenagers with
      spinal muscular atrophy (SMA). However, what has been tested in these studies,
      with the Wechsler Intelligence Scale for Children-Revised (Wechsler, 1974)
      performance scale, does not deal with the spatial capacities that co-occur with
      the advent of self-produced locomotion. Indeed, various studies have shown that
      occurrence of locomotion in infancy is correlated with the development of
      visuospatial cognitive competencies, suggesting that locomotor experience might
      play a central role in spatial development, especially in the realm of manual
      search for hidden objects. It is thus of interest to assess spatial search skills
      in SMA young children suffering total deprivation of locomotor experience. Twelve
      Type-2 SMA children with a mean age of 30 months were compared with controls with
      respect to their spatial search skills in a memory-for-locations task. In this
      search task, hiding containers were rotated 180 degrees before search was
      permitted. The performance obtained with the SMA group did not differ from that
      obtained in the healthy control group. SMA patients searched correctly for a
      hidden object in the 3-choice search task. Locomotor impairment does not appear
      to be a key risk factor for dramatic slowing down or deviation in the development
      of spatial search skills, as assumed by some authors. Further research is needed
      to identify the alternative pathways to normal spatial development that are used
      by SMA young children.

PMID- 12233940
TI  - Relations between visual and auditory continuous performance tests in a clinical
      population: a descriptive study.
AB  - Increased interest in auditory continuous performance tests (CPTs) exists despite
      the absence of a clear understanding about this procedure. The relation between
      auditory and visual CPTs and associations with IQ, achievement, and memory are
      evaluated in a referred sample of 634 children, ages 5.5 to 17.9. Age effects are
      found with CPT performance, regardless of modality. Total number correct or
      number of commissions correlations across tasks were greater than within-task
      number correct-number of commissions relations. The mean visual minus auditory
      correct difference score was 7.01; the mean commission difference score was -.85.
      Difference scores decreased with age and were not consistently related to other
      measures. Those with the lowest number correct on both CPTs (<25th percentile)
      were younger and had weaker short-term auditory memory and verbal learning
      skills; those falling in the problem quartile on commissions (>75th percentile)
      were younger and had poorer reading, verbal memory, and verbal learning. Total
      error scores (omissions + commissions) were inversely related to age. The
      auditory CPT has clinical utility, but other factors must be considered.

PMID- 12233941
TI  - Reading and phonological awareness in reading-disabled adults.
AB  - Sixty-eight students with reading disabilities (RDs) and 55 non-reading-disabled
      university undergraduates composed the sample. Students with RDs met either low
      achievement (LA) or regression-based discrepancy (D) criteria. In addition to IQ
      and reading decoding measures, all participants received measures of phonological
      awareness (PA), confrontation naming, and verbal fluency. Consistent with
      expectations, the D and LA subgroups did not differ from one another, and both
      performed worse than students without RD on phonological measures. However, only
      the LA subgroup performed worse on measures of confrontation naming and verbal
      fluency. Subgroups of readers who had LA without an IQ-achievement discrepancy
      (LA-no D) and readers who had both LA and a discrepancy (LA + D), performed worse
      than readers who had a discrepancy but whose reading achievement was above the
      16th percentile (D-no LA) on measures of PA, naming, and fluency; this subgroup
      did not differ from students without RDs. These results question the utility of
      determining RD in adults solely on the basis of IQ-achievement discrepancy
      criterion without regard to other linguistic skills or absolute reading level.

PMID- 12233942
TI  - Antiretroviral therapy in HIV-infected pregnant women and their infants: current
      interventions and challenges.
AB  - Advances in antiretroviral therapy for human immunodeficiency virus (HIV)
      infected pregnant women have improved maternal health and successfully reduced
      perinatal transmission from 25% to less than 5%. Maternal treatment is
      individualized and based on physical and laboratory evaluations. Three categories
      of drugs are currently approved for use in HIV disease including: (11 nucleoside
      and nucleotide reverse transcriptase inhibitors; (2) non-nucleoside reverse
      transcriptase inhibitors; and (3) protease inhibitors. Treatment decisions during
      pregnancy are complex and require consideration of the physiologic changes of
      pregnancy, drug interactions, possible maternal and fetal side effects, and
      psychosocial issues that influence adherence to the chosen therapy.

PMID- 12233943
TI  - Steroid use during pregnancy.
AB  - Health care providers and pregnant women share a concern for protecting the fetus
      from unnecessary and potentially teratogenic influences. Since the introduction
      of steroids for the induction of fetal surfactant production, there has been
      considerable experience in the use of corticosteroids during pregnancy. While the
      use of corticosteroids for surfactant induction in the preterm fetus has become
      commonplace, steroids are used for other obstetric and medical indications during
      pregnancy. Thus, finding a balance between drug benefits and possible side
      effects remains a critical issue.

PMID- 12233944
TI  - Use of antidiabetes agents in pregnancy: current practice and controversy.
AB  - Prior to the discovery of insulin, the combination of diabetes and pregnancy was
      considered potentially lethal. Advances in the care of diabetes, combined with
      advances in antepartum fetal testing, have reduced maternal and perinatal
      mortality outcomes to levels expected in nondiabetic pregnancies. As new oral
      antidiabetes medications are introduced, the safety and efficacy of using them
      during pregnancy are under investigation. This article describes the oral
      medications currently available to treat diabetes, reviews the body of research
      available on these agents, and discusses current recommendations and
      controversies.

PMID- 12233945
TI  - Vancomycin and gentamicin in neonates: hindsight, current controversies, and
      forethought.
AB  - The use of both vancomycin and gentamicin in the treatment of suspected or
      documented neonatal infections, while routine, is a challenge for bedside and
      advanced practice nurses caring for neonates in intensive care units. A review of
      the background information surrounding neonatal infections as well as the
      history, intended use, and the pharmacokinetic and pharmacodynamic properties of
      vancomycin and gentamicin is presented with the goal of aiding in proper
      treatment with these two medications. Specific attention is given to doses in
      special situations, means of drug monitoring, strategies for avoiding antibiotic
      resistance, alternative medication choices, and areas for future investigation.

PMID- 12233946
TI  - Moving toward safer practice: reducing medication errors in neonatal care.
AB  - Medication errors are a concern in all areas of health care, including neonatal
      units. In order to reduce errors and move toward safer practice, it is essential
      for clinicians to focus less on assigning blame to individuals and more on how
      these problems occurred. Only then will we fully understand the contributing
      factors and comprehensively address the reduction of medication errors. This
      article examines historical perspectives, contributing factors, and strategies
      for developing safer practice in neonatal care.

PMID- 12233947
TI  - Bias in qualitative research designs.

PMID- 12233948
TI  - Is there a doctor in the house?

PMID- 12233949
TI  - Body mass index and mortality in aboriginal Australians in the Northern
      Territory.
AB  - OBJECTIVE: To assess the association between body mass index and the risk of all
      cause and disease-specific mortalities in Australian Aborigines in a remote
      community. DESIGN: A community based cohort study. PARTICIPANTS AND SETTING: 744
      Aboriginal adults aged 20 to 77 years in a remote community in Northern
      Territory. Eighty-seven deaths occurred during the follow-up period of 5,040.8
      person-years. MEASURES: Mortality data for the period of 1992 and June 2000 were
      collected. Mortality rate ratios for each body mass index quartile was determined
      using a Cox proportional hazards model with adjustment for age, sex, and smoking
      and drinking status. RESULTS: An inverse relationship between BMI quartiles and
      the risk of all-cause, natural, and non-CVD mortality was found. Adjusted rate
      ratios (95% CI) of all-cause mortality were 0.92 (0.54-1.59), 0.71 (0.40-1.26)
      and 0.38 (0.19-0.75) for second, third and fourth BMI quartiles, respectively,
      with the first quartile as the reference. The fourth BMI quartile had the lowest
      risk of mortality with adjusted rate ratios of 0.38, 0.28, and 0.16 for deaths
      from all-cause, natural, and non-CVD, respectively. However, the associations
      between BMI and CVD and renal deaths did not reach statistical significance.
      CONCLUSIONS: BMI and mortality are inversely associated in Aboriginal adults in a
      remote community. Individuals with relatively higher BMI have a lower risk of
      death.

PMID- 12233951
TI  - Suicide differentials in Australian males and females by various measures of
      socio-economic status, 1994-98.
AB  - OBJECTIVES: To investigate Australian suicide differentials in males and females
      by three area-based measures of socio-economic status (SES). METHODS: Suicide
      data for 1994-98 were used to investigate area-based gradients of SES for the
      Index of Relative Socio-Economic Disadvantage (IRSED) (an overall measure of
      SES), the Index of Economic Resources (IER), and the Index of Education and
      Occupation (IEO), using Poisson regression models adjusting for age, country-of
      birth and urban-rural residence. RESULTS: After adjusting for age, country-of
      birth and urban-rural residence, significant increasing linear trends in suicide
      risk from high to low quintiles of SES were evident in males for the IRSED (an
      average multiplicative increase in suicide risk of 8% per quintile), IER (9%
      increase) and IEO (5% increase). For females, there was no evident SES gradient
      for the IRSED after adjusting for age, country-of-birth and urban-rural
      residence, but a significant positive linear trend from high to low quintiles of
      SES was found for the IER (6% increase per quintile). A significant decreasing
      linear trend (increasing suicide risk with increasing SES) was evident for the
      IEO (30% per quintle). CONCLUSION: Male suicide is positively associated with all
      three measures of SES examined. Female suicide is significantly associated with
      the IER (positive association) and IEO (negative), and because of this is not
      associated with the overall measure of SES. These findings partly explain why
      female suicide has been found to be poorly correlated with area-based measures of
      SES. IMPLICATIONS: Specific components of area-based socio-economic status
      provide a clearer picture of socio-economic suicide differentials in Australian
      females, with implications for population-based preventive strategies.

PMID- 12233950
TI  - Socio-economic mortality differentials in Sydney over a quarter of a century,
      1970-94.
AB  - OBJECTIVE: To examine trends in socio-economic differentials in all-cause
      mortality in Sydney over a 25-year period (1970-94). METHODS: Five measures of
      single indicators (two for occupation, two for education and one for income) and
      a composite measure of socio-economic disadvantage based on Census data (the
      Australian Bureau of Statistics' Index of Relative Socio-Economic Disadvantage)
      were used as indicators of socio-economic status by local govemment area. The
      relationship between mortality and socio-economic status was examined using
      quintiles based on these six measures of socio-economic status. RESULTS: Socio
      economic differentials in mortality were evident for males and females for all
      periods, and over the 25-year period the relative socio-economic differentials
      did not decline. For males, the socio-economic status differential in mortality
      widened, irrespective of socio-economic status indicator used, whereas for
      females it widened only when certain socio-economic indicators were used:
      occupation (unemployment measure) and income, but was not significant for the
      other single indicators or for the composite indicator. CONCLUSIONS: Sydney
      trends of widening inequalities are generally similar to those reported for
      Britain and for other industrialised countries, suggesting that this is a common
      phenomenon and that policies to reduce health inequalities over the past quarter
      of a century have not been effective.

PMID- 12233952
TI  - The health of the Australian workforce: 1998-2001.
AB  - OBJECTIVE: To describe the health of the Australian workforce in relation to
      occupational status. METHODS: Data on 9,167 workers, collected between 1998 and
      2001, were obtained from the Campbell National Health Monitor, a cross-sectional
      national, health survey. Professional, white-collar and blue-collar workers were
      compared on five health outcomes: self-rated health, long-and short-term
      conditions, reduced activity days and work absences. RESULTS: One in 10 workers
      (M:11%; F:10%) rated their health as poor. Two-thirds (M: 60%; F: 64%) reported
      long-term conditions with four in five (M:77%; F: 83%) reporting short-term
      conditions. Smaller proportions took health-related actions, with 21% of men and
      28% of women reducing their activity, and 17% of men and 20% of women taking time
      off work in a given month. Occupational inequalities in self-rated health were
      evident for both men and women, with professionals reporting the best health and
      blue-collar workers the worst (p < 0.001). Male, but not female, white- and blue
      collar workers also had higher rates of short-term conditions (OR 1.25, 1.06-1.50
      and 1.25, 1.07-1.46, respectively) and reduced activity days due to health (OR
      1.43, 1.20-1.71 and 1.25, 1.07-1.47, respectively) compared with professionals.
      However, blue-collar workers reporting health problems were the least likely to
      take time off work (poor health: p = 0.043; short-term conditions: p = 0.001;
      long-term conditions: p = 0.003). CONCLUSIONS AND IMPLICATIONS: Blue-collar
      workers are the least healthy occupational grouping. They are also the most
      likely to present to work unwell. With employment conditions rapidly changing,
      better understanding of the impact of these changes on workers' health is vital.

PMID- 12233953
TI  - Working together to reduce health inequalities: reflections on a collaborative
      participatory approach to health research.
AB  - With mounting evidence that health problems are related to social inequalities,
      health researchers increasingly need to engage with disadvantaged and
      marginalised groups. These groups can present specific challenges to conventional
      research method. This paper reflects on the need for health researchers to meet
      these challenges in order to gain a deeper understanding of the ways in which
      social disadvantage affects people's health, and to develop appropriate
      interventions for those groups. Models of collaborative, participatory and action
      research are defined on a continuum. The value of a collaborative participatory
      approach to health research is discussed. Key processes in collaboration are
      outlined, and some of the methodological tensions and ethical issues that arise
      when using such an approach are addressed. The recognition that power is directly
      related to knowledge lies at the heart of the collaborative participatory
      research project. Collaborative participatory research offers a strategy that
      embraces self-determination, encourages and even demands ongoing consultation and
      negotiation, and provides opportunities for capacity-building and empowerment in
      the communities involved in the research. Nowhere is such a strategy more needed
      in Australia today than for research with Indigenous communities.

PMID- 12233954
TI  - Research methods, evidence and public health.
AB  - In theory, our research questions should drive our choice of method. In practice,
      we know this is not always the case. At various stages of the research process
      different factors may apply to restrict the choice of research method. These
      filters might include a series of inter-related factors such as the political
      context of the research, the disciplinary affiliation of the researchers, the
      research setting and peer-review. We suggest that as researchers conduct research
      and encounter the various filters they come to know the methods that are more
      likely to survive the filtering process. In future projects they may favour these
      methods. Public health problems and research questions may increasingly be framed
      in the terms that can be addressed by a restricted array of methods. Innovative
      proposals - where new methods are applied to old problems, old methods to new
      areas of inquiry and high-quality interdisciplinary research - may be unlikely to
      survive the processes of filtering. This may skew the public health knowledge
      base, limiting public health action. We argue that we must begin to investigate
      the process of research. We need to document how and why particular methods are
      chosen to investigate particular sets of public health problems. This will help
      us understand how we know what we know in public health and help us plan how we
      may more appropriately draw upon a range of research methods.

PMID- 12233955
TI  - The SF-12 in the Australian population: cross-validation of item selection.
AB  - OBJECTIVE: To cross-validate the selection of the questionnaire items for the SF
      12 in an Australian sample. METHOD: The sample comprised respondents with
      complete data on the SF-36 summary measures and the 12 items that comprise the SF
      12 (n = 17,671) from the 1995 Australian National Health Survey. Two sets of
      mental and physical summary scales were analysed, based on either scoring from
      Australian normative data or the standard United States normative data scoring.
      Forward stepwise linear regression analyses of weighted data provided the
      proportion of variance in the summary scales explained by the SF-12 items.
      RESULTS: The SF-12 items predicted at least 90% of the variance in both the
      physical and mental summary scales of the SF-36, whether they were scored with
      Australian or United States normative data. IMPLICATIONS: The SF-12 is an
      appropriate substitute for the SF-36 when the summary scales are of interest but
      a briefer instrument is required.

PMID- 12233956
TI  - Surveillance of work-related disorders in Australia using general practitioner
      data.
AB  - OBJECTIVES: The focus of this paper is to compare the main findings regarding
      work-related problems managed in general practice with those of other data
      sources in the occupational and public health arenas that provide some
      information on work-related disorders in Australia, in order to examine the
      implications for surveillance and prevention. METHODS: Data on work-related
      disorders managed in general practice were obtained from a larger study of
      general practice activity that involved a cluster random sample of all
      significantly active general practitioners in Australia from 1998 to 2000. These
      data were compared with other Australian datasets containing information on work
      related disorders. RESULTS: Despite a predominance of musculoskeletal conditions
      in all the data sources, general practitioner data provided a different picture
      of work-related disorders in the community to workers' compensation information
      from the National Data Set of Compensation-based Statistics (NDS) and the limited
      information on work-related disorders available from other studies of general
      practice and emergency departments. The mix of conditions was different in many
      aspects, and diseases were much less common in the NDS. CONCLUSIONS: General
      practitioner data supplement data provided by other sources, particularly the
      NDS, and make an important contribution to filling some of the gaps in
      information about work-related diseases and more minor work-related injuries.
      IMPLICATIONS: General practitioners could prove a useful supplementary source of
      data on work-related disorders, but the optimal content of, and method for
      obtaining, these data is not clear.

PMID- 12233957
TI  - Results from the 4th National Clients of Treatment Service Agencies census:
      changes in clients' substance use and other characteristics.
AB  - OBJECTIVE: The 2001 Clients of Treatment Service Agencies (COTSA) census, the
      fourth since 1990, was conducted to enable a comparison of the drug and alcohol
      related problems being treated over an 11-year period. METHOD: The 24-hour census
      was conducted on Wednesday 2 May 2001 in all Australian States and Territories.
      All agencies providing treatment for drug and alcohol problems in Australia were
      asked to provide demographic, treatment and substance use information about all
      clients treated on census day. The data were analysed with frequencies and basic
      descriptive statistics. RESULTS: Of the agencies surveyed, 90.3% responded. The
      census suggests that, among the treatment population, the mean age of substance
      users has decreased and the proportion of clients who are women has increased.
      Treatment for opiate, cannabis and amphetamine problems increased; treatment for
      alcohol problems decreased. Substance use patterns differed according to sex,
      age, size of the population centre, and Indigenous status. CONCLUSIONS AND
      IMPLICATONS: Changes among the treatment population reflect changes in
      demographics and substance use among the broader drug-using community, with the
      exception of the presentation of alcohol problems for treatment. The reasons for
      the apparent decline in treatment for alcohol problems are not clear, although a
      number of factors, such as changes in treatment strategies and facilities and
      relative increases in other substance use problems, are considered. Any decrease
      in treatment for a significant health problem such as alcohol use disorder will
      have considerable public health implications.

PMID- 12233958
TI  - Fatal methadone toxicity: signs and circumstances, and the role of
      benzodiazepines.
AB  - OBJECTIVE: To describe the signs and symptoms and circumstances of fatal
      methadone toxicity and investigate the role of benzodiazepines in these deaths.
      METHODS: Data were extracted from 1994 New South Wales (NSW) coronial files and
      cause of death established independently. Cases were grouped according to the
      likely source of methadone. Data describing the clinical history and
      circumstances of death were extracted from witnesses' and police statements.
      RESULTS: Methadone contributed to the deaths of 57 of the 87 adult coronial cases
      in which it was detected in NSW in 1994. The most commonly reported early signs
      of severe methadone toxicity were ataxia, slurred speech and evident euphoria.
      The late signs were unconsciousness, loud snoring and brown pulmonary oedema
      fluid coming from the mouth or nose. Death occurred an average 5.1 and 6.0 hours
      after oral ingestion and intravenous injection of methadone, respectively.
      Benzodiazepines were significantly more likely to have contributed to deaths from
      methadone toxicity among maintenance patients and people taking methadone tablets
      for pain relief than deaths involving diverted methadone syrup and deaths to
      which methadone did not contribute (OR 4.8, 95% 1.7 to 14.4). CONCLUSIONS AND
      IMPLICATIONS: Benzodiazepines may contribute to deaths from methadone toxicity by
      increasing upper airways obstruction. Victims would have had a greater chance of
      survival if they had either been placed in the coma position or given mouth-to
      mouth ventilation and an ambulance had been called. Benzodiazepines are more
      likely to contribute to fatal methadone toxicity in newly admitted maintenance
      patients and those taking methadone tablets for pain relief.

PMID- 12233959
TI  - Methadone-related deaths in Western Australia 1993-99.
AB  - OBJECTIVES: To describe methadone-related deaths in Western Australia from 1993
      to 1999 and determine differences between deaths in methadone maintenance
      treatment (MMT) in the public and private sectors. METHOD: Review of coronial and
      clinical data for all cases identified by methadone detected from toxicological
      analysis of post-mortem samples between January 1993 and December 1999. RESULTS:
      Eighty-four methadone-related deaths were identified. The majority (64%) were
      accidental; 74% of these were caused by a combination of drug effects. Overall,
      benzodiazepines were present in 74% of all decedents. Thirty-six (43% of all
      decedents) were registered in MMT when they died. Twenty-two decedents were
      registered with Next Step, of whom two died in the first week of treatment. In
      contrast, 14 decedents were registered with the CBMP, of whom eight died in the
      first week of treatment. The mortality rate in MMT peaked in 1998 (7.7 per 1,000
      clients treated), one year after expansion into the private sector. A range of co
      existing health conditions were present among decedents including: blood-bome
      viruses (BBVs), chronic pain/injury, asthma, epilepsy, diabetes, obesity, kidney
      disease, cardiac disease, pancreatitis, gall stones, paraplegia, cerebral palsy,
      schizophrenia, depression, suicidal ideation and arthritis. CONCLUSIONS: Overall,
      methadone-related mortality did not increase significantly despite an increase in
      the population in MMT. Polydrug use, in particular the use of benzodiazepines in
      combination with methadone, was a major risk factor for premature mortality.
      IMPLICATIONS: More attention is needed to reduce the use of benzodiazepines in
      combination with methadone. Decentralisation of methadone services into general
      practice must be carefully monitored to minimise the risk of mortality.

PMID- 12233960
TI  - Epidemiology of physical activity participation among New South Wales school
      students.
AB  - OBJECTIVE: To examine the prevalence and socio-demographic distribution of
      physical activity among New South Wales school students in Years 8 and 10.
      METHODS: Cross-sectional survey of 2,026 randomly selected NSW high school
      students in 1997. The survey participants self-reported their physical activity
      participation during a normal week in summer and winter school terms. RESULTS:
      During summer school terms, 80.9% and 85.9% of Year 8 and Year 10 boys,
      respectively, and 80.8% and 77.7% of Year 8 and Year 10 girls, respectively, were
      adequately active. During winter school terms, 75.6% and 84.0% of Year 8 and Year
      10 boys, respectively, and 69.4% and 66.0% of Year 8 and Year 10 girls,
      respectively, were adequately active. The associations between socio-economic
      status, urban/rural place of residence and physical activity participation were
      neither strong nor consistent. There were complex relationships between physical
      activity participation and cultural background among boys, and large differences
      between different cultural groups of girls and large declines in participation
      from Year 8 to Year 10 among girls. CONCLUSIONS: Although the majority of boys
      and girls are adequately active, it is clear that a smaller proportion of girls
      than boys are vigorously active, particularly during winter. There were no clear
      differences across tertiles of SES or place of residence, but there were
      significant differences between girls from different cultural backgrounds.
      IMPLICATIONS: Efforts to increase the proportion of young people who are
      vigorously active should emphasise the needs and interests of girls, particularly
      those from Middle-Eastem and Asian cultural backgrounds.

PMID- 12233961
TI  - The effect of a smoke-free law on restaurant business in South Australia.
AB  - BACKGROUND: Despite evidence to the contrary from overseas research, the
      introduction of smoke-free legislation in South Australia (SA), which required
      all restaurants to go smoke-free in January 1999, sparked concerns among the
      hospitality industry about loss of restaurant business. This study aimed to
      determine whether the law had a detrimental impact on restaurant business in SA.
      METHODS: Using time series analysis, we compared the ratio of monthly restaurant
      turnover from restaurants and cafes in SA to (a) total retail tumover in SA
      (minus restaurants) for the years 1991 to 2001 and (b) Australian restaurant
      tumover (minus SA, Westem Australia and the Australian Capital Territory) for the
      years 1991-2000. RESULTS: There was no decline in the ratio of (a) SA restaurant
      turnover to SA retail turnover or (b) SA restaurant tumover to Australian
      restaurant turnover. CONCLUSION: The introduction of a smoke-free law applying to
      restaurants in SA did not adversely affect restaurant business in SA.

PMID- 12233962
TI  - Residential camps as a setting for nutrition education of Australian girls.
AB  - OBJECTIVE: To implement a planned nutrition education program aiming to promote
      healthy eating and consumption of a variety of foods in a residential camp
      setting for Australian girls aged 9-15 years. METHODS: 1,600 girls attending a
      seven-day residential camp in Queensland (2000) participated in a program
      involving the provision of healthy, tasty foods based on the Australian Dietary
      Guidelines for Children and Adolescents and a nutrition education package for use
      at the camp restaurants each evening that included nutrition information together
      with individual 'passport booklets involving puzzles and questions with
      incentives for completion. Process and impact evaluations were conducted by
      surveying a sample of participants using questionnaires and focus groups.
      RESULTS: Of those surveyed, 77% felt they had leamed something from the health
      promotion material; 94% said they had changed their eating habits to include more
      core food groups during the camp, with more than 40% stating they had increased
      vegetable consumption compared with their usual intake. However, approximately
      60% of campers were apparently unaware of the incentives offered and less than
      30% demonstrated completion of their passports. CONCLUSIONS: Barriers to the
      involvement of this target group in the health promotion activities need to be
      explored further. Involvement and training of key personnel is suggested to
      ensure consistent implementation and encouragement for all participants. Long
      term behaviour changes outside the camp environment should also be assessed in
      any future programs. IMPLICATIONS: Using residential camp settings to target
      children is an innovative strategy for nutrition education. Integration of such
      strategies into longer time frame programs may benefit participants and improve
      effectiveness of nutrition education programs aimed at this group.

PMID- 12233963
TI  - Using school management plans to track engagement in a public health
      intervention.

PMID- 12233964
TI  - Sex behind the prison walls.

PMID- 12233965
TI  - Keeping the turf (wars) trimmed.

PMID- 12233966
TI  - Rediscovering the value of the journal club.

PMID- 12233967
TI  - Practices and predictors of analgesic interventions for adults undergoing painful
      procedures.
AB  - BACKGROUND: Research is limited on analgesic practices associated with the
      commonly performed procedures of turning, inserting central venous catheters,
      removing wound drains, changing dressings on nonburn wounds, suctioning the
      trachea, and removing femoral sheaths. OBJECTIVES: To determine types of
      analgesics administered for procedures, the prevalence and amounts of drugs
      given, and factors predictive of analgesic administration. METHODS: Pain was
      assessed before and immediately after procedures. Analgesic, sedative, and
      anesthetic agents administered within 1 hour before and/or during each procedure
      were noted RESULTS: A total of 5957 adult patients at 164 national and 5
      international sites participated. Pain intensity increased at the time of
      procedure for all procedures. More than 63% of patients received no analgesics.
      Less than 20% received opiates; mean total dose of opiate was 6.44 mg (SD, 8.96
      mg). Only 10% of patients received combination therapy. Factors associated with
      the likelihood of receiving opiates were pain intensity before a procedure,
      femoral sheath removal, being white, and the duration of a procedure. Patients
      less likely to receive opiates had a medical diagnosis or were having tracheal
      suctioning. Only 14.5% of the variance in the amount of opiate administered was
      explained by factors entered into multiple regression models. Type of procedure
      was the only significant predictor of amount of opiate administered. CONCLUSIONS:
      Most patients were not intentionally medicated even though pain intensity
      increased during their procedure. When used, analgesic amounts were low, and
      combination therapy was infrequent. Clinical trials are needed to evaluate
      optimal pain management for patients undergoing procedures.

PMID- 12233968
TI  - Use of intercostal bupivacaine with epinephrine after surgery to decrease use of
      narcotics and duration of intubation.
AB  - BACKGROUND: Postoperative pain plays a significant part in the recovery of
      patients after open heart surgery. OBJECTIVE: To determine if the use of
      intercostal bupivacaine with epinephrine is associated with decreases in use of
      narcotics and intubation times after open heart surgery. METHODS: A randomly
      selected experimental group of 25 patients received injections of bupivacaine
      with epinephrine in the intercostal tissues before chest closure in open heart
      surgery. A control group of 22 patients received no bupivacaine, only standard
      care. Postoperative use of narcotics and intubation times were determined for
      both groups. RESULTS: Compared with the control group, the group given
      bupivacaine with epinephrine used significantly less narcotics (P=.008) and had
      significantly shorter intubation times (P=.003). CONCLUSION: Injection of
      intercostal bupivacaine with epinephrine before chest closure in open heart
      surgery decreases use of narcotics and length of intubation postoperatively, thus
      speeding up recovery times.

PMID- 12233969
TI  - The synergy model and the role of clinical nurse specialists in a multihospital
      system.
AB  - The role of clinical nurse specialists was formalized in the 1950s; the goal was
      to prepare inpatient, bedside nurses who would serve acutely ill patients via
      consultation and direct care. Clinical nurse specialists were to be expert
      clinicians, consultants, educators, and researchers. In the early stages of
      practice development, the focus was the specific needs of the assigned unit or
      floor. Organizational restructuring led to the elimination of many positions for
      clinical nurse specialists, with a shift of some of the nurses' responsibilities
      to others (ie, managers) or the abandonment of some of the traditional roles.
      Recently, a reversal occurred in this trend, evidenced by a steady growth in the
      demand for these advanced practice nurses by organizations seeking to improve
      patients' outcomes while remaining fiscally responsible. This demand led to
      changes in role expectations and expanded the responsibilities of clinical nurse
      specialists to a system-wide or organization-wide level. Contemporary practice of
      clinical nurse specialists is not well reflected in traditional role definitions
      or commonly accepted practice models. The Synergy Model, developed by the AACN
      Certification Corporation, was introduced as a way of linking certified practice
      to patients' outcomes. The model describes 8 nurse characteristics and 3 spheres
      of influence. This article describes how a group of clinical nurse specialists
      applied the model to successfully change from a unit-based to a multisystem
      practice.

PMID- 12233970
TI  - Acute care nurse practitioners: creating and implementing a model of care for an
      inpatient general medical service.
AB  - Changes in medical education and healthcare reimbursement are recent threats to
      most academic medical centers' dual mission of patient care and education.
      Financial pressures stem from reduced insurance reimbursement, capitation, and
      changes in public funding for medical residency education. Pressures for
      innovation result from increasing numbers of patients, higher acuity of patients,
      an aging population of patients with complex problems, and restrictions on
      residency workloads. A framework for addressing the need for innovation in the
      medical service at a large academic medical center is presented. The framework
      enables acute care nurse practitioners to provide inpatient medical management in
      collaboration with a hospitalist. The model's development, acceptance, successes,
      pitfalls, and evaluation are described. The literature describing the use of
      nurse practitioners in acute care settings is reviewed.

PMID- 12233971
TI  - Impact of a prolonged surgical critical illness on patients' families.
AB  - BACKGROUND: Long-term effects on patients' families after a prolonged stay in a
      surgical intensive care unit are unclear. We hypothesized that illnesses
      requiring more than 7 days' stay in the surgical intensive care unit would have
      significant, long-lasting effects on patients' families that would be related to
      patients' functional outcome. METHODS: All patients who stayed in the general
      surgery intensive care unit 7 days or more between July 1, 1996, and June 30,
      1997, were enrolled. A total of 128 patients met the entry criteria, and families
      of surviving patients were interviewed at baseline and 1, 3, 6, and 12 months
      later. Maximum dysfunction/impact was compared with patients' functional outcome.
      RESULTS: Significant disturbances in the families' lives occurred throughout the
      12 months of this study. Almost 60% of responding families provided a moderate or
      large amount of caregiving between 1 and 9 months after a prolonged illness,
      44.9% had to quit work after 1 month, and more than 36.7% of families had lost
      savings after 1 year. Some families moved to a less expensive home, delayed
      educational plans, or delayed medical care for another family member.
      CONCLUSIONS: An acute surgical illness that results in a prolonged stay in an
      intensive care unit has a substantial effect on patients' families that is
      maximal between 1 and 3 months and parallels the patient's functional outcome.
      Systems that provide support to both patients and their families should be
      emphasized in the hospital and after discharge.

PMID- 12233972
TI  - Outcomes of and resource consumption by high-cost patients in the intensive care
      unit.
AB  - BACKGROUND: Care of patients in an intensive care unit is among the most costly
      in hospitals. Little is known about high-cost patients within the intensive care
      unit or their outcomes of care. OBJECTIVES: To examine outcomes of and resource
      consumption by high-cost adult patients who received care in an intensive care
      unit at an academic medical center. METHODS: Data on patients admitted during the
      period January 1, 1995, through June 30, 1999, were analyzed retrospectively. An
      intensive care unit database, the hospital discharge data set, and a cost
      accounting data set were used to determine the total intensive care unit cost for
      the hospitalization. Patients were then stratified into cost deciles. Hospital
      and intensive care unit outcomes for patients in the top decile were compared
      with those of patients in the other deciles. RESULTS: Cost data were available on
      10,606 of the 11,244 patients who received care in an intensive care unit.
      Patients in the top decile accounted for 48.7% of all intensive care unit costs,
      and 67.6% of this group survived to discharge despite prolonged care. Patients
      transferred from an outside hospital were more likely to be in the top decile,
      have a longer stay in the intensive care unit, or die than were the other
      patients. CONCLUSIONS: A small group of patients accounts for a
      disproportionately higher amount of intensive care unit resources but has a
      relatively high survival rate. This cohort should be treated as an intact group
      that is not amenable to traditional cost-cutting measures.

PMID- 12233973
TI  - Outpatient costs of medications for patients with chronic heart failure.
AB  - BACKGROUND: The outpatient costs of medications prescribed for chronic heart
      failure are high and are often borne by individual patients. Lack of financial
      resources may force noncompliance with use of medications. OBJECTIVE: To compare
      the outpatient costs of medications for patients with different New York Heart
      Association classifications of chronic heart failure. METHODS: The charts of 138
      patients with chronic heart failure were reviewed retrospectively. Outpatient
      costs of medications were obtained from the Web sites of commercial pharmacies.
      Medications were classified by type according to the system of the American Heart
      Association. A mean cost for each classification of medication was used for
      analysis. RESULTS: The overall mean monthly cost of medications for chronic heart
      failure was $438. Patients with class II and class III chronic heart failure had
      the highest costs: $541 and $514, respectively. Analysis of variance indicated
      that the differences in monthly costs of medications between the patients with
      the 4 stages of chronic heart failure were significant (F = 4.86, P = .003). A
      post hoc Scheffe test revealed significant differences in costs between patients
      with class I and patients with class II heart failure (P = .02) and between
      patients with class I and those with class III heart failure (P = .02).
      CONCLUSIONS: The outpatient costs of medications for chronic heart failure are
      significant. Ability to pay for prescribed medications must be determined.
      Healthcare professionals must maintain an awareness of the costs of medications
      and patients' ability to pay.

PMID- 12233974
TI  - Caring for the silent patient.

PMID- 12233975
TI  - High-sensitivity C-reactive protein is the most effective prognostic measurement
      of acute coronary events.
AB  - Inflammation plays a major role in the pathogenesis of arterial atherosclerosis.
      The stages of atheroma development from early recruitment of leukocytes and fatty
      streaks to the unstable plaque and finally rupture are mediated by the
      inflammatory process. Several markers of vascular wall inflammation that can
      predict future risk of plaque rupture have been identified. However, these lack
      the specificity of CRP. Numerous large-scale prospective studies established hs
      CRP as a strong biochemical marker for the prediction of future first or
      recurrent coronary events. A Food and Drug Administration-approved method for
      measuring hs-CRP is currently available.

PMID- 12233976
TI  - Intermittent conduction disturbances.

PMID- 12233977
TI  - Clinical and translational research: introduction to the special issue.
AB  - This special issue represents an effort by the journal Experimental and Clinical
      Psychopharmacology to emphasize its interdisciplinary mission by encouraging the
      writing of articles on clinical research and the interchange between basic and
      clinical research on mental illness and the addictions. This special issue opens
      with a commentary from A. I. Leshner (2002), retired director of the National
      Institute on Drug Abuse, which emphasizes the importance of translating research
      findings into clinical practice. Four review articles and 12 original research
      reports provide a broad sampling of contemporary clinical research, including
      behavioral therapy, pharmacotherapy, psychiatric comorbidity, and special
      populations, and also illustrate linkages between clinical research and basic
      fields of inquiry, including behavioral theory, neuropsychology,
      neuropharmacology, and statistics.

PMID- 12233978
TI  - Experimental and clinical psychopharmacology: National Institute on Drug Abuse's
      clinical research agenda.
AB  - Studies of drugs and behavior are a core component of virtually every portfolio
      within the broad purview of the National Institute on Drug Abuse (NIDA).
      Moreover, psychopharmacological research is an important vehicle for advancing
      understanding of how drugs of abuse produce their effects, particularly including
      addiction. However, as with all major public health issues, simply understanding
      the issue is not enough. NIDA's psychopharmacology projects, therefore, span
      basic, clinical, and applied (e.g., medication development) research activities.
      These include the establishment of a nationwide clinical trials network designed
      to provide an infrastructure to test both behavioral and psychopharmacological
      treatments in a real-life practice setting with diverse patients.

PMID- 12233979
TI  - Applying laboratory research: drug anticipation and the treatment of drug
      addiction.
AB  - Basic research concerning drug tolerance and withdrawal may inform clinical
      practice, and vice versa. Three areas that integrate the work of the laboratory
      and the clinic are discussed: (a) drug overdose, (b) cue exposure treatment of
      addiction, and (c) pharmacological treatment of withdrawal symptoms. The areas
      are related in that they indicate the contribution of drug-paired cues to the
      effects of addictive drugs and the role of Pavlovian conditioning of drug effects
      in drug tolerance and withdrawal symptoms.

PMID- 12233980
TI  - How treatments for pathological gambling can be informed by treatments for
      substance use disorders.
AB  - Substance use disorders and pathological gambling share similarities in terms of
      diagnostic criteria, epidemiology, and clinical course. However, relatively few
      studies have evaluated the efficacy of treatments for gambling disorders. As
      interest in pathological gambling grows, adaptation of effective treatments from
      the field of substance abuse may advance the study of treatment for pathological
      gambling. This article reviews the similarities and differences between
      pathological gambling and substance use disorders. It describes psychotherapeutic
      and pharmacological treatments for substance use disorders and their translation
      to pathological gambling. Future research should consider investigating the onset
      and course of pathological gambling within the context of other psychiatric
      disorders, biological abnormalities associated with gambling, and combined
      effects of psychotherapy and pharmacotherapy in the treatment of this disorder.

PMID- 12233981
TI  - Neurocognitive impairment associated with alcohol use disorders: implications for
      treatment.
AB  - Between 50% and 80% of individuals with alcohol use disorders experience mild to
      severe neurocognitive impairment. There is a strong clinical rationale that
      neurocognitive impairment is an important source of individual difference
      affecting many aspects of addiction treatment, but empirical tests of the direct
      influence of impairment on treatment outcome have yielded weak and inconsistent
      results. The authors address the schism between applied-theoretical perspectives
      and research evidence by suggesting alternative conceptual models of the
      relationship between neurocognitive impairment and addiction treatment outcome.
      Methods to promote neurocognitive recovery and ways in which addiction treatments
      may be modified to improve psychosocial adaptation are suggested. Specific
      suggestions for future research that may help clarify the complex relations
      between neurocognitive impairment and addiction treatment are outlined.

PMID- 12233982
TI  - Clinical uses of naltrexone: a review of the evidence.
AB  - The implication of the opioidergic system in the pathogenesis of various
      substance use disorders has led to renewed interest in expanding the clinical
      uses of naltrexone, an opioid antagonist. This article examines the evidence for
      the efficacy of naltrexone in a variety of substance use and psychiatric
      disorders. Naltrexone can be an effective treatment for alcohol and opioid
      dependence if issues of compliance are adequately addressed. Thus far, no
      definitive role has been found for naltrexone in the treatment of other
      psychiatric disorders. Further research needs to be done in self-injurious
      behavior, gambling, cocaine, and nicotine dependence.

PMID- 12233983
TI  - A reinforcement-based therapeutic workplace for the treatment of drug abuse:
      three-year abstinence outcomes.
AB  - Long-term Therapeutic Workplace effects were evaluated in heroin- and cocaine
      dependent, unemployed, treatment-resistant young mothers. Participants were paid
      to work or to train in the Therapeutic Workplace but had to provide drug-free
      urine samples to gain daily access. Participants (N = 40) were randomly assigned
      to a Therapeutic Workplace or usual care control group. Therapeutic Workplace
      participants could work for 3 years. Relative to controls, Therapeutic Workplace
      participants increased cocaine (28% vs. 54% negative; p = .04) and opiate (37%
      vs. 60% negative; p = .05) abstinence on the basis of monthly urine samples
      collected until 3 years after intake. The Therapeutic Workplace can be an
      effective long-term treatment of cocaine and heroin addiction in poor and
      chronically unemployed young mothers.

PMID- 12233984
TI  - Contingent monetary reinforcement of smoking reductions, with and without
      transdermal nicotine, in outpatients with schizophrenia.
AB  - This study was conducted to examine the effects of contingent monetary
      reinforcement (CM) for smoking reduction, with and without transdermal nicotine,
      on cigarette smoking in individuals with schizophrenia. Fourteen outpatients
      participated in each of 3 conditions: (a) CM combined with 21 mg transdermal
      nicotine, (b) CM combined with placebo patch, and (c) noncontingent reinforcement
      combined with placebo patch. Each condition lasted 5 days. Carbon monoxide levels
      were measured 3 times daily, and nicotine withdrawal symptoms were measured once
      daily in each condition. Results indicated that CM reduced smoking but that 21 mg
      transdermal nicotine did not enhance that effect. These results offer further
      evidence supporting the efficacy of CM for reducing smoking among people with
      schizophrenia, but higher doses of nicotine replacement therapy, or another
      pharmacotherapy, may be needed to enhance that effect.

PMID- 12233985
TI  - Predicting natural resolution of alcohol-related problems: a prospective
      behavioral economic analysis.
AB  - This study investigated whether the relative allocation of discretionary monetary
      expenditures to alcoholic beverages versus savings (presumed to reflect relative
      preferences for immediate vs. delayed rewards) before quitting abusive drinking
      predicted natural resolution among untreated problem drinkers. Drinking, life
      events, income, and expenditures were assessed for the year before resolution and
      again 1 and 2 years later (N = 50). Compared with those who relapsed,
      participants who remained resolved at 2 years reported proportionally more pre
      resolution discretionary expenditures on savings and less on alcohol. Income and
      expenditures were similar across groups. The findings support the predictive
      utility of this functional index of relative reward preferences that operate over
      variable time horizons and suggest that temporal discounting is an important
      process in addictive behavior change.

PMID- 12233986
TI  - Using latent-variable models to analyze smoking cessation clinical trial data: an
      example among the methadone maintained.
AB  - The relationship between tobacco and illicit drug use was examined among 166
      methadone-maintained persons participating in a smoking cessation intervention.
      Latent-growth latent-variable models showed a significant relationship during
      treatment between rates of change in heroin and rates of change in tobacco use,
      with increased heroin use corresponding with increased tobacco use. Although
      levels of cocaine use were related to levels of tobacco use, there was no
      significant relationship between the rates of change of the 2 substances. A more
      traditional longitudinal structural equation model demonstrated a significant
      relationship between more heroin use during treatment and negative smoking
      cessation outcomes at 6-month follow-up. Findings demonstrate the utility of
      latent-growth models for analyzing short-term clinical trial data and strongly
      suggest that successful smoking cessation in this population requires a
      concurrent focus on reducing heroin use.

PMID- 12233987
TI  - Multimodal evaluation of risperidone for destructive behavior: functional
      analysis, direct observations, rating scales, and psychiatric impressions.
AB  - Risperidone, an atypical neuroleptic, has become a popular option for treating
      destructive behaviors of persons with developmental disabilities. A few studies
      have been conducted that evaluate the effects of risperidone on destructive
      behavior; however, none of these studies have combined objective measures with
      rating scales to evaluate the effects of risperidone on destructive behavior
      across home and clinical settings. This study evaluated the wide range of effects
      of risperidone on destructive behavior of 2 persons with developmental
      disabilities using weekly functional analysis sessions, daily observations,
      hourly home data, weekly rating scales, and monthly psychiatric impressions.
      Results indicate that risperidone does decrease destructive behavior and that,
      for the most part, all of the various measures yielded similar results.

PMID- 12233988
TI  - Carbamazepine in the treatment of cocaine dependence: subtyping by affective
      disorder.
AB  - Studies investigating carbamazepine (CBZ) in the treatment of cocaine dependence
      have been inconsistent. In this study, cocaine-dependent individuals with (n =
      57) and without (n = 82) affective disorder were compared in a 12-week, double
      blind, placebo-controlled trial. Urine drug screens (UDS) and self-report of drug
      use were collected weekly. Affective symptoms were measured monthly. Subjects
      receiving CBZ attended more medication sessions (p = .03). The CBZ-treated
      affective group had a trend toward fewer cocaine-positive UDS (p = .08) and a
      significantly longer time to first cocaine use (p = .06). CBZ treatment did not
      have any impact on cocaine use in individuals without affective disorders.

PMID- 12233989
TI  - Double-blind placebo-controlled trial of methylphenidate in the treatment of
      adult ADHD patients with comorbid cocaine dependence.
AB  - In this 12-week double-blind placebo-controlled trial of methylphenidate (MTP)
      versus placebo in 48 cocaine-dependent attention-deficit/hyperactivity disorder
      (ADHD) adults, the authors sought to determine whether MTP would be safe, control
      ADHD symptoms, and affect cocaine use. Efficacy indexes revealed significantly
      greater ADHD symptom relief in the MTP group. There were no group differences in
      self-reported cocaine use, urinalysis results, or cocaine craving. Because of the
      relatively small sample size, the results are preliminary. However, we found that
      MTP improved subjective reports of ADHD symptoms and did not worsen cocaine use
      while participants were in treatment.

PMID- 12233991
TI  - Gender differences among pathological gamblers seeking treatment.
AB  - This study investigated gender differences among treatment-seeking pathological
      gamblers. During treatment intake, 115 pathological gamblers completed the
      Addiction Severity Index (ASI; A. T. McLellan et al., 1985), including a section
      on gambling severity, as well as the South Oaks Gambling Screen (H. R. Lesieur &
      S. B. Blume, 1987). When age and income were controlled, gender differences
      emerged in ASI gambling, alcohol, and legal scores. Men initiated gambling, began
      gambling regularly, tried to stop gambling, and first entered gambling treatment
      at a younger age than women. Women were more likely to be living with someone
      with a gambling or drinking problem but themselves had fewer alcohol and legal
      problems. Results suggest that gender differences exist in the initiation of
      gambling dysfunction and its psychosocial correlates. Understanding these
      differences may assist in developing treatments that address differential needs
      of male and female pathological gamblers.

PMID- 12233990
TI  - Do men outperform women in smoking cessation trials? Maybe, but not by much.
AB  - Using data from 4 smoking cessation trials conducted from 1988 to 2000, the
      authors investigated whether men are more successful than women in quitting
      smoking. Odds ratios indicated that the abstinence rates were not significantly
      different for men and women. Thus, there may be little value to diverting
      research funds from efforts to develop more effective treatments for both men and
      women to efforts to explain a very small gender effect associated with existing
      treatments. However, it may be appropriate to make gender comparisons for new
      therapies for nicotine dependence. The authors recommend against analyses of
      gender differences in studies that do not account for gender in their research
      designs.

PMID- 12233992
TI  - Gender differences in psychiatric comorbidity among adolescents with substance
      use disorders.
AB  - The authors examined gender differences in rates of comorbid psychiatric
      disorders among adolescents with I or more psychoactive substance use disorders.
      Baseline diagnostic data were obtained from 135 adolescents, ages 12 to 19, and
      their parents-guardians, who participated in a study to develop and efficacy test
      Integrated Family and Cognitive-Behavioral Therapy. Rates of attention
      deficit/hyperactivity disorder and conduct disorder were higher among drug
      abusing male adolescents compared with drug-abusing female adolescents. However,
      high rates of disruptive behavior disorders also characterized drug-abusing
      female adolescents. Similarly, drug-abusing female adolescents exhibited a higher
      rate of major depression compared with drug-abusing male adolescents. However,
      rates of dysthymia, double depression (i.e., major depression and dysthymia), and
      bipolar disorder were equivalent between genders.

PMID- 12233993
TI  - Examining possible gender differences among cocaine-dependent outpatients.
AB  - Potential differences in sociodemographics, drug use, and measures of treatment
      outcome were examined among 137 male and 51 female cocaine-dependent outpatients.
      More women than men were unemployed, received public assistance, and were living
      with their children. Women reported fewer years of regular cocaine use, spending
      less money per week on cocaine, less prior treatment for cocaine abuse, and were
      more likely than men to test positive for cocaine at intake. With respect to
      other drug use, fewer women than men reported using sedatives and tested positive
      for sedatives at intake. Women reported a lower frequency of alcohol use before
      intake, and fewer women than men met criteria for cannabis dependence. Men and
      women experienced comparable improvement during the course of treatment and
      follow-up.

PMID- 12233994
TI  - Nonproblem drinking outcomes in adolescents treated for alcohol use disorders.
AB  - Change to nonproblem drinking was studied in 159 adolescents (70% male)
      presenting for alcohol use disorders (AUDs) treatment. A community sample (n =
      148,47% male) also was assessed. Clinical participants had a current AUD at
      baseline; 1 year later, 17% remained abstinent, 60% had at least 1 AUD symptom
      (problem drinkers), and 23% were drinking but had no AUD symptoms (nonproblem
      drinkers). Drinking among the nonproblem drinkers decreased and was lower than in
      the problem drinkers. Nonproblem drinkers increased in psychosocial functioning
      and decreased in the number of illicit drugs used relative to problem drinkers
      and generally did not differ from the abstainers. The results suggest alternative
      views of treatment goals, relapse, and treatment outcome in adolescents.

PMID- 12233995
TI  - Parasitological prevalence of bovine trypanosomosis in Kindo Koisha district,
      Wollaita zone, south Ethiopia.
AB  - A cross sectional survey to determine the distribution and prevalence of
      trypanosomosis was conducted in Kindo Koisha district, in the Wollaita zone in
      southern Ethiopia. A total of 1 008 adult cattle was examined at eight different
      localities. Dark field examination of the buffy coat, as well as stained thin
      blood film examination and packed cell volume (PCV) evaluation were the
      diagnostic techniques used. The overall prevalence of bovine trypanosomosis was
      15 %. Among the positive animals, 108 (71.1%), 43 (28.4%) and 1 (0.6%) were due
      to Trypanosoma vivax, Trypanosoma congolense and mixed infection (T. vivax and T.
      congolense), respectively. The infection rate of T. vivax and T. congolense
      varied significantly (P < 0.01). The mean PCV of the positive and negative
      animals ranged between 18.3-32.1% and 26.8-33.4%, respectively. The mean PCV of
      negative animals (28 %) was significantly higher than the mean PCV of positive
      animals (22.3%) (P < 0.001). There was an inverse association of PCV with the
      prevalence of trypanosomosis (P > 0.05). The herd average PCV values of each site
      decreased with increasing proportion of the positive herds of that particular
      site. Of the diagnostic tests employed, the microhaematocrit buffy coat technique
      is relatively sensitive and it has an added advantage of indicating the general
      condition of the animal by haematocrit measurement. In view of the risk of
      trypanosomosis, a control intervention through the strategic application of
      appropriate trypanocidal drugs is recommended. A tsetse fly control scheme to
      reduce host-tsetse fly contact is equally as important as chemotherapy and
      chemoprophylaxis against trypanosomosis.

PMID- 12233996
TI  - Seasonal abundance of four Culicoides spp. (Diptera: Ceratopogonidae) at Al-Ahsa
      oasis, Eastern Province, Saudi Arabia.
AB  - This report constitutes the first study of Culicoides spp. and their seasonal
      abundance at Al-Ahsa, the largest oasis in the Eastern Province of Saudi Arabia.
      New Jersey light traps were used to collect the midges at Mastock farm and Al
      Mansura village. The mean monthly abundance was determined from October 1993 to
      October 1994. The mean monthly number per trap reached its minimum value during
      January 1994, increasing gradually from February to reach its maximum value
      during September 1994. During the study period, the following species were
      collected: Culicoides schultzei group (September), non-spotted group of
      Culicoides (September), Culicoides imicola (May) and Culicoides newstaedi
      (March). The potential importance of the Culicoides spp. in relation to arboviral
      activity in Saudi Arabia is discussed.

PMID- 12233997
TI  - An overview of the eradication of Brucella melitensis from KwaZulu-Natal.
AB  - Brucella melitensis is a Gram-negative bacterium whose primary hosts are goats
      and sheep. Like the other BrucelIa spp., with the exception of Brucella ovis, it
      is not particularly host specific as it is pathogenic for a variety of other
      mammal species including humans. In humans the disease caused by it is rated as
      one of the most important zoonoses. Three outbreaks have been recorded in goats
      and sheep in South Africa; the first outbreak occurred in sheep in 1965 in the
      Mpumalanga and Northern Provinces (then both part of the Transvaal Province), the
      second occurred in sheep in 1989 near Pretoria, Gauteng Province, and the third
      and current outbreak was diagnosed in a flock of goats in northern KwaZulu-Natal
      in September 1994. Following the initial diagnosis of B. melitensis in north
      eastern KwaZulu-Natal, a serological survey was conducted in order to identify
      foci of infection in the goat and sheep populations. Six positive foci were
      identified. In March 1996 a test-and-slaughter eradication campaign was initiated
      in these areas. Initial test results revealed a prevalence of between 1.23% and
      4.02 %. All positive animals were identified and slaughtered. Eradication
      programmes were repeated between March 1996 and June 2000, in the populations at
      risk, and the disease prevalence was reduced in all the affected populations.

PMID- 12233998
TI  - Isolation of serovar C-3 Haemophilus paragallinarum from Zimbabwe: A further
      indication of the need for the production of vaccines against infectious coryza
      containing local isolates of H. paragallinarum.
AB  - Various isolates of Haemophilus paragallinarum, collected from a severe outbreak
      of infectious coryza in poultry from Zimbabwe, were serotyped and were found to
      belong to serovar C-3. Previously, isolates were serotyped using polyclonal
      antiserum produced against serogroup reference strains (0083 for serogroup A,
      0222 for serogroup B and Modesto, or H-18 for serogroup C) of H. paragallinarum.
      In this case, polyclonal antiserum produced against these reference isolates were
      used, as well as polyclonal antiserum that has been raised specifically against
      the serovar C-3 isolate 46 C-3. When using the latter serum at a 1 in 50
      dilution, no cross-reaction with other members of serogroup C were found. The
      severity of the disease outbreak in Zimbabwe, the vaccination history of the
      infected flocks on the sites and the isolation of the uniquely southern African
      serovar C-3, further highlights the need for vaccines composed of local isolates
      to control infectious coryza in regions where vaccination failures occur.

PMID- 12233999
TI  - Occurrence of concurrent trypanosomosis, theileriosis, anaplasmosis and
      helminthosis in Friesian, Zebu and Sahiwal cattle in Uganda.
AB  - An epidemiological investigation was conducted on farms in Tororo and Soroti
      districts of Uganda from January to February 2000 to determine the cause of
      reported persistent mortality of cattle. Blood and faecal material of 98 cattle
      comprising of 33 Friesians, 58 Zebu and 7 Sahiwal were examined. Results revealed
      that seven (7.1 %) cattle had trypanosome infection, mainly due to Trypanosoma
      vivax and T. brucei, 17 (17.3%) Fasciola infection, 28 (28.6%) gastrointestinal
      nematode infection, 33 (33.7%) Theileria sp. infection and 13 (13.3%) Anaplasma
      marginale infection. Mixed infections were detected in 30%, 20.6% and 43 % of the
      Friesian, Zebu and Sahiwal cattle respectively. Anaemia (PCV < 25) was detected
      in 24%, 19% and 14% of the Friesian, Zebu and Sahiwal cattle respectively.
      Persistent mortality of cattle on these farms could have been due to either
      single or mixed parasitic infections probably exacerbated by malnutrition.

PMID- 12234000
TI  - Seasonal availability of gastrointestinal nematode larvae to cattle on pasture in
      the central highlands of Kenya.
AB  - The type and level of infective strongylid nematode larvae on pasture were
      monitored fortnightly from July 1995 to June 1996 in the central highlands of
      Kenya. The number of larvae on pasture was moderate, reaching > 1,200 kg(-1) dry
      matter of grass during the period of, and soon after, the rains, and remained low
      in the dry seasons. The number of larvae on pasture was directly related to the
      rain-fall pattern which was found to be the most important factor for the
      development of eggs and free-living stages. Haemonchus was the predominant genus,
      followed in decreasing order by Trichostrongylus, Cooperia, Oesophagostomum and
      Bunostomum. The mean total adult worm burdens of tracer calves released at
      monthly intervals were related to the levels of herbage larvae and there was a
      positive correlation between faecal worm egg counts and worm burdens (r = 0.58)
      during the study period. These results indicate that a reduction in the
      contamination of pasture with nematode eggs before the rains could result in
      pastures carrying fewer larvae and thus form the basis of effective worm control
      programmes for cattle.

PMID- 12234001
TI  - The Kumm isolate of Ehrlichia ruminantium: in vitro isolation, propagation and
      characterization.
AB  - An effective culture system for Ehrlichia (Cowdria) ruminantium comb. nov. was
      first established in 1985 and many stocks were subsequently isolated and
      propagated in vitro. A notable exception, however, was the Kumm isolate that
      resisted all attempts at in vitro culture until the successful experiment
      described here. In one experiment white blood cells were harvested from
      heparinized blood derived from a sheep infected with the Kumm isolate. The cells
      were added to DH 82 cells and incubated at 37 degrees C. The high metabolic
      activity of the DH 82 cells necessitated that cell growth be retarded by the
      addition of cycloheximide. Colonies were first detected 19 days after culture
      initiation and, once the cultures were established, they could be passaged every
      3 days. Bovine and sheep endothelial cells were readily infected with culture
      supernatant obtained from the infected DH 82 cells. In a further experiment
      another sheep was infected, using a higher dose of the same batch of Kumm
      stabilate, and we attempted to infect several different cell lines: these were DH
      82 cells, bovine aorta (BA 886) cells, sheep brain endothelial (SBE 189) cells
      and sheep fibroblastoid cells (E2). Ten days after culture initiation only the E2
      cells had become positive for E. ruminantium. Culture supernatant from the first
      cultured isolate (Kumm-1) was less virulent for mice than that of the second
      cultured isolate (Kumm-2) which killed all mice. Upon molecular characterization
      with E. ruminantium 16S probes we found that Kumm-1 hybridized with a Senegal 16S
      genotype probe, whereas Kumm-2 hybridized only with an Omatjenne 16S genotype
      probe. The original stabilate used to infect the sheep hybridized with both
      probes. These results clearly indicate that two different stocks had been
      isolated in culture.

PMID- 12234002
TI  - Non-immune control of trypanosomosis: in vitro oxidative burst of PMA- and
      trypanosome-stimulated neutrophils of Boran and N'Dama cattle.
AB  - An in vitro assay that measures the generation of superoxide anions (O2-) was
      used to assess the level of oxidative burst of phorbol myristate acetate (PMA)-
      and trypanosome-stimulated neutrophils isolated from healthy Boran and N'Dama
      cattle, and those infected with Trypanosoma congolense. PMA stimulation of
      healthy bovine neutrophils resulted in between 300-400 % increase in O2-
      generation. Neutrophils of Boran cattle exhibited slightly higher but
      insignificant O2- generation capacity than those of the N'Dama breed. In vitro
      stimulation by trypanosomes of neutrophils isolated from Trypanosoma congolense
      infected cattle caused significant increases in O2- generation, especially on
      days 14, 28 and 42 post-infection, of both breeds of cattle. No significant
      differences were observed in O2- generation capacity of the neutrophils of both
      breeds of infected cattle throughout the period of assay. The results of this
      study have shown that PMA and trypanosomes do cause an enhanced in vitro
      oxidative burst, hence trypanosome phagocytosis and killing activity of
      neutrophils. Neutrophils have been shown to play very significant roles in
      parasite clearance, hence reduction of trypanosome parasitaemia. The rates of
      both in vitro generation of O2- and trypanosome phagocytosis over time did not
      differ significantly between Boran and N'Dama breeds of cattle, even during T
      congolense infection in this study. Hence, it may be inferred that sustained and
      higher parasitaemia, more pronounced neutropenia, inadequate bone marrow response
      and less effective trypanosome-specific immune response, rather than defective
      neutrophil trypanosome destruction, may be the problem of trypanosusceptible
      cattle breeds.

PMID- 12234003
TI  - Virulence of South African isolates of Haemophilus paragallinarum. Part 1: NAD
      dependent field isolates.
AB  - The virulence of four South African field isolates of NAD-dependent Haemophilus
      paragallinarum, representing the four serovars known to occur in that country,
      was investigated. During this study an alternative challenge model for infectious
      coryza was used, in which the infectivity as well the virulence of different
      isolates could be evaluated. The challenge model consisted of the direct
      challenge, via intrasinus injection of one chicken in a row of interconnected
      layer cages, containing 10 chickens, which are subsequently infected by natural
      routes. A scoring system of the clinical signs was established in which a score
      is given to the ability of the isolate to produce clinical signs in the challenge
      birds. The mean daily disease score for the flock can be calculated and plotted
      on a graph to give a graphic representation of the disease profile. A mean
      disease score, calculated over a 20-day examination period can be calculated.
      Isolates can then be compared to each other, either graphically or by a
      comparison of the mean disease scores. It has been demonstrated using this
      scoring system that the South African serogroup C isolates appear to be more
      virulent than the South African serogroup A or B isolates. It was further
      established that the serovar C-3 isolate appeared to be the most virulent.

PMID- 12234004
TI  - Virulence of South African isolates of Haemophilus paragallinarum. Part 2:
      naturally occurring NAD-independent field isolates.
AB  - Naturally occurring NAD-independent variants of Haemophilus paragallinarum, which
      have been isolates from poultry showing clinical signs of infectious coryza, were
      used to determine their virulence using a newly developed challenge model for
      infectious coryza. It was established that the NAD-independent isolates belonging
      to a particular serogroup, were less virulent when compared to the virulence of
      the NAD-dependent isolates from the same serogroup. It was shown that the
      virulence of the NAD-independent isolates belonging to serogroup C and serogroup
      A were very similar to each other. This differs to the results obtained with NAD
      dependent isolates reported on previously, in which the serogroup C isolates were
      found to be more virulent then the serogroup A isolates.

PMID- 12234005
TI  - Acaricide resistance profiles of single- and multi-host ticks from communal and
      commercial farming areas in the Eastern Cape and North-West Provinces of South
      Africa.
AB  - A field study (February 2000 to August 2001) was conducted on communal and
      commercial farms in the Eastern Cape and North-West Provinces of South Africa to
      detect the levels of tick resistance to commonly used acaricides. The larvae
      obtained from engorged females of the one-host tick Boophilus decoloratus, the
      two-host tick Rhipicepalus evertsi evertsi and the three-host ticks Amblyomma
      hebraeum and Rhipicephalus appendiculatus were tested against various
      concentrations of amitraz, chlorfenvinphos and cypermethrin using the Shaw Larval
      Immersion Test method. Ticks from the communal farms showed higher levels of
      resistance to cypermethrin and some resistance to chlorfenvinphos whilst no
      resistance was detected against amitraz. However, ticks from commercial farms
      were equally resistant to amitraz, chlorfenvinphos and cypermethrin. The B.
      decoloratus populations tested were considerably more resistant to all the
      acaricides tested than the R. evertsi evertsi, A. hebraeum and R. appendiculatus
      populations. This supports the hypothesis that single-host ticks develop
      resistance faster than multi-host ticks. This trend was recorded on most of the
      farms where single- and multi-host ticks co-existed. It was concluded that the
      use of acaricides at high frequencies and high concentrations was one of the main
      causes of tick resistance in the study areas. Possible factors which caused the
      resistance problems are discussed and acaricide management strategies
      recommended.

PMID- 12234006
TI  - Archaeal integrative genetic elements and their impact on genome evolution.
AB  - Integrases encoded in archaeal genomes can be classified into seven families on
      the basis of their sequences. They constitute a super-family of tyrosine DNA
      recombinases together with a number of bacterial integrases and they are likely
      to be responsible for the formation of integrated elements in archaeal
      chromosomes. An integrated element is defined as possessing an integrase, a block
      of foreign genes, and a direct repeat at the two ends with one repeat unit
      overlapping a tRNA gene. There are two types of archaeal integrated elements, the
      SSV viral type, including those that carry the partitioned integrase gene, intN
      and intC, and the pNOB8 type, including those with a tRNA gene overlapping the
      attL site 5' prior to an integrase gene. Both known and unknown genes are present
      in these integrated elements and their encoded proteins may have facilitated the
      adaptation of archaea during evolution.

PMID- 12234007
TI  - Alkane biodegradation in Pseudomonas aeruginosa strains isolated from a polluted
      zone: identification of alkB and alkB-related genes.
AB  - Pseudomonas aeruginosa strains that grow on crude oil as the sole source of
      carbon and energy were isolated from an environment in Morocco polluted by
      petroleum refinery effluents. The twenty isolates grew on saturated alkanes from
      C12 to C22. Three of the isolates were also able to grow on low molecular weight
      C6 to C10 n-alkanes, but the other 17 strains were not. The strains were tested
      for alkB and a/kB-related genes encoding alkane-1-monooxygenase (alkane
      hydroxylase). Oligonucleotide primers specific for the alkB gene of strain P.
      putida (GPo1 ) and for the alkB1 and alkB2 genes of P. aeruginosa strain PAO1
      allowed amplification from the P. aeruginosa isolates of fragments similar to
      alkB1 and alkB2 genes of strain PAO1. Only 3 strains carried an alkB gene very
      similar to that of strain GPo1, and these strains were the same ones that could
      utilise C6 to C10 n-alkanes.

PMID- 12234008
TI  - Gluconacetobacter diazotrophicus, a sugar cane endosymbiont, produces a
      bacteriocin against Xanthomonas albilineans, a sugar cane pathogen.
AB  - Gluconacetobacter diazotrophicus in liquid culture secretes proteins into the
      medium. Both medium containing Gluconacetobacter protein and a solution of this
      protein after acetone precipitation appeared to inhibit the growth of Xanthomonas
      albilineans in solid culture. This apparent inhibition of bacterial growth has,
      in fact, been revealed to be lysis of bacterial cells, as demonstrated by
      transmission electron microscopy. Fractionation of the Gluconacetobacter protein
      mixture in size-exclusion chromatography reveals a main fraction with lysozyme
      like activity which produces lysis of both living bacteria and isolated cell
      walls.

PMID- 12234009
TI  - Use of potassium tellurite for testing the survival and viability of Pseudomonas
      pseudoalcaligenes KF707 in soil microcosms contaminated with polychlorinated
      biphenyls.
AB  - This study shows that the oxyanion tellurite TeO3(2-) can be used as a tool to
      detect and quantify the release in soil microcosms of Pseudomonas
      pseudoalcaligenes KF707, a strain spontaneously resistant to tellurite with a
      minimal inhibitory concentration (MIC) of 150 microg ml(-1). KF707 cells which
      carry the genes for degradation of a wide range of polychlorinated biphenyl
      congeners (PCBs) were used for inoculation of laboratory microcosms prepared with
      two different PCB-contaminated soils (Ci/s and Di/s) in the presence or absence
      of biphenyl as carbon source. In all microcosms supplemented with biphenyl,
      significant survival of strain KF707 was noted over a time period of 35 days;
      conversely, in microcosms containing Ci/s soil without biphenyl addition a rapid
      decrease in KF707 inoculated cells was observed. By comparing the number of
      inoculated KF707 cells with the number of indigenous bacteria growing on biphenyl
      (IBGB) of both Ci/s and Di/s microcosms, it could be concluded that the
      KF707/IBGB ratio is a relevant parameter in determining the fate of the added
      strain. The efficacy of potassium tellurite as a selective marker to monitor
      strain KF707 in laboratory microcosms was confirmed by ARDRA analyses of the 16S
      rDNA, while the isolated indigenous bacteria growing on biphenyl were identified
      as members of three different species of the genus Pseudomonas. We also report
      that in microcosms inoculated with KF707 cells in the absence of biphenyl, only
      low chlorinated biphenyls were degraded.

PMID- 12234011
TI  - Evaluation of symbiotic effectiveness of various Rhizobium cicer strains.
AB  - Five local and seven standard strains of Rhizobium cicer were compared in terms
      of their efficiency in increasing the nitrogen content of the chickpea. Shoot dry
      weight, nodule number, nodule dry weight, protein and total nitrogen contents
      were taken as the parameters of plant productivity. Different combinations of the
      strains that were found to be promising (385, 620, Y-29 and 3379) were next
      employed. The maximum increase in total nitrogen content was only 3.5-fold in
      single infection whereas an increase as great as 35-fold was recorded for
      multiple infections. The double infection with Y-29 and 385 as well as the triple
      infection with Y-29, 620 and 3379 gave rise to the maximum values.
      Competitiveness of the strains in mixed infections was determined through their
      recovery from root surfaces and nodules and their subsequent identification. The
      effects of soil pH and of varying the concentration of some minerals on the
      outcome of symbiosis were also reported.

PMID- 12234010
TI  - Relationship of chemical structures of textile dyes on the pre-adaptation medium
      and the potentialities of their biodegradation by Phanerochaete chrysosporium.
AB  - Azo dye derivatives of azobenzene constitute the largest group of dyes used in
      the textile industry and possess recalcitrant chemical groups, such as those of
      azo and sulphonic acid. Some microorganisms are able to degrade these aromatic
      compounds. In the present work, decolourisation of culture media containing azo
      dyes by the ligninolytic fungus Phanerochaete chrysosporium was achieved under
      nitrogen-limited conditions. The dyes used in the study are derivatives of meta-
      or para-aminosulphonic or aminobenzoic acids and include in their structures
      groups such as guaiacol or syringol, which are bioaccessible to the lignin
      degrading fungus P. chrysosporium. The aim of this study was to pre-adapt the
      microorganism to the structure of the dyes and to establish the relationships of
      the chemical structure of the dye present in the pre-adaptation medium with the
      chemical structure of the dye to be degraded. The azo dye used in the pre
      adaptation medium that gave the best overall decolourisation performance was a
      meta-aminosulphonic acid and guaiacol derivative. The azo dye derivative of a
      meta-aminobenzoic acid and syringol showed a better performance in the
      decolourisation assays. Preliminary GC-MS studies indicated the formation of a
      nitroso substituted catechol metabolite, a precursor of aromatic ring cleavage,
      which was confirmed to occur by an enzymatic assay. The presence of this type of
      metabolite allows the establishment of a possible metabolic pathway towards
      mineralisation.

PMID- 12234012
TI  - Determination of the stability of protein pools from the cell wall of fungi.
AB  - Stability of the protein populations present in the cell wall of three
      ascomycetous fungi Candida albicans, Saccharomyces cerevisiae and Yarrowia
      lipolytica was investigated. Cell wall proteins were either labeled with biotin
      or radiolabeled with amino acids, and chased for a period of time representing
      several generations. Proteins linked by non-covalent or covalent bonds were
      separated and their turnover was analyzed. No significant turnover took place
      during the chase period, and in fact radioactive proteins were accumulated in the
      wall during the period possibly by transfer through the secretory pathway. This
      transfer did not involve de novo protein synthesis; it was inhibited by azide,
      and by incubation of a sec1 mutant of S. cerevisiae at the non-permissive
      temperature. It is concluded that proteins bound to the cell wall are stable and
      that there is no precursor-product relationship among those linked by non
      covalent bonds and the covalently bound ones.

PMID- 12234013
TI  - Destabilized green fluorescent protein for monitoring transient changes in
      mycobacterial gene expression.
AB  - The green fluorescent protein (GFP) is a useful reporter for the study of gene
      expression and protein localisation within living cells. The stability of GFP
      permits its intracellular accumulation and detection, but renders it less useful
      for assessing transient changes in gene expression. We have developed a
      destabilized form of GFP for monitoring gene expression in mycobacteria. By
      fusing to the C-terminal end of GFP an 11 amino acid peptide encoded by the E.
      coli ssrA gene, we have developed a form of GFP that exhibits gradual, time
      dependent degradation within the fast-growing species Mycobacterium smegmatis.
      This unstable variant of GFP detected transient changes in the activity of the
      stress-induced Mycobacterium tuberculosis sigE promoter; by contrast, unmodified
      GFP only detected a delayed 'switch-on' of this promoter upon exposure to acid
      stress. Both forms of the protein displayed equivalent stability in the slow
      growing species Mycobacterium bovis bacille Calmette-Guerin (BCG), suggesting
      differing recognition of the ssrA-encoded peptides in slow- and fast-growing
      mycobacteria. This system will facilitate studies exploring dynamic changes in
      mycobacterial gene expression.

PMID- 12234014
TI  - Tight junctions and compositionally related junctional structures in mammalian
      stratified epithelia and cell cultures derived therefrom.
AB  - The occurrence of extended tight junction (TJ) structures, including zonulae
      occludentes (ZO), and the spatial arrangement of TJ proteins in stratified
      mammalian epithelia has long been controversially discussed. Therefore, we have
      systematically examined the localization of TJ proteins in diverse stratified
      epithelial tissues (e.g., epidermis, heel pad, snout, gingiva, tongue, esophagus,
      exocervix, vagina, urothelium, cornea) of various species (human, bovine,
      rodents) as well as in human cell culture lines derived from stratified
      epithelia, by electron microscopy as well as by immunocytochemistry at both the
      light and the electron microscopic level, using antibodies to TJ proteins such as
      occludin, claudins 1 and 4, protein ZO-1, cingulin and symplekin. We have found
      an unexpected diversity of TJ-related structures of which only those showing
      colocalization with the most restricted transmembrane TJ marker protein,
      occludin, are presented here. While in epidermis and urothelium occludin is
      restricted to the uppermost living cell layer, TJ-related junctions are abundant
      in the upper third or even in the majority of the suprabasal cell layers in other
      stratified epithelia. Interfollicular epidermis contains, in the stratum
      granulosum, extended, probably continuous ZO-like structures which can also be
      traced at least through the Henle cell layer of hair follicles. Similar apical ZO
      like structures have been seen in the upper living cell layers of all other
      stratified epithelia and cell cultures examined, but in most of them we have
      noticed, in addition, junctional regions showing relatively broad, ribbon-like
      membrane contacts which in cross-section often appear pentalaminar, with an
      electron-dense middle lamella ("lamellated TJs", coniunctiones laminosae). In
      suprabasal layers of several stratified epithelia we have further observed TJ
      protein-containing junctions of variable sizes which are characterized by a 10-30
      nm dense lamina interposed between the two membranes ("sandwich junctions";
      iuncturae structae). Moreover, we have often observed variously sized regions in
      which the intermembrane distance is rather regularly bridged by short rod-like
      elements ("cross-bridged cell walls"; parietes transtillati), often in close
      vicinity of TJ-related structures or desmosomes. The significance of these
      structures and their possible biological importance are discussed.

PMID- 12234015
TI  - Targeting of carbonic anhydrase IV to plasma membranes is altered in cultured
      human pancreatic duct cells expressing a mutated (deltaF508) CFTR.
AB  - Human pancreatic duct cells secrete HCO3- ions mediated by a Cl-/HCO3- exchanger
      and a HCO3- channel that may be a carbonic anhydrase IV (CA IV) in a channel-like
      conformation. This secretion is regulated by CFTR (Cystic Fibrosis Transmembrane
      conductance Regulator). In CF cells homozygous for the deltaF508 mutation, the
      defect in targeting of CFTR to plasma membranes leads to a disruption in the
      secretion of Cl- and HCO3 ions along with a defective targeting of other
      proteins. In this study, we analyzed the targeting of membrane CA IV in the human
      pancreatic duct cell line CFPAC-1, which expresses a deltaF508 CFTR, and in the
      same cells transfected with the wild-type CFTR (CFPAC-PLJ-CFTR6) or with the
      vector alone (CFPAC-PLJ6). The experiments were conducted on cells in the
      stationary phase the polarized state of which was checked by the distribution of
      occludin and actin. We show that both cell lines express a 35-kDa CA IV at
      comparable levels. Analysis of fractions of plasma membranes purified on a
      Percoll gradient evidenced lower levels of CA IV (8-fold) in the CFPAC-1 than in
      the CFPAC-PLJ-CFTR6 cells. Quantitative analyses showed that 6- to 10-fold fewer
      cells in the CFPAC-1 cell line exhibited membrane CA IV-immunoreactivity than in
      the CFPAC-PLJ-CFTR6 cell line. Taken together, these results suggest that the
      targeting of CA IV to apical plasma membranes is impaired in CFPAC-1 cells. CA
      IV/gamma-adaptin double labeling demonstrated the presence of CA IV in the trans
      Golgi network (TGN) of numerous CFPAC-1 cells, indicating that trafficking was
      disrupted on the exit face of the TGN. The retargeting of CA IV observed in CFPAC
      PLJ-CFTR6 cells points to a relationship between the traffic of CFTR and CA IV.
      On the basis of these observations, we propose that the absence of CA IV in
      apical plasma membranes due to the impairment in targeting in cells expressing a
      deltaAF508 CFTR largely contributes to the disruption in HCO3- secretion in CF
      epithelia.

PMID- 12234016
TI  - Subunit composition and functional properties of G-protein heterotrimers on rat
      chromaffin granules.
AB  - Heterotrimeric G-proteins at the plasma membrane serve as switches between
      heptahelical receptors and intracellular signal cascades. Likewise endomembrane
      associated G-proteins may transduce signals from intracellular compartments
      provided they consist of a functional trimer. Using quantitative immunoelectron
      microscopy we found heterotrimeric G-protein subunits Galpha2, Galpha(q/11),
      Gbeta2 and Gbeta5 to reside on secretory granules in chromaffin cells of rat
      adrenal glands. Thus rat chromaffin granules are equipped with functional G
      proteins that consist of a specific alpha-, beta- and probably gamma-subunit
      combination. Serotonin uptake into a crude rat chromaffin granule preparation was
      inhibited by activated Galphao2 (10 nM) to nearly the same extent as by GMppNp
      (50 microM) whereas GDPbetaS was ineffective. The data support the idea that
      vesicular G-proteins directly regulate the transmitter content of secretory
      vesicles. In this respect Galphao2 appears to be the main regulator of vesicular
      momoamine transporter activity.

PMID- 12234017
TI  - TGFbeta1 -mediated epithelial to mesenchymal transition is accompanied by
      invasion in the SiHa cell line.
AB  - It has recently been suggested by several investigators that the epithelial
      mesenchymal transition-inducing capacity of TGFbetas contributes to invasive
      transition of tumors at later stages of carcinogenesis. In the present study, we
      examined the possibility of TGFbeta1-stimulated epithelial-mesenchymal transition
      in SiHa cell line, detailed molecular events in the process, and its possible
      contribution to the invasive transition of tumors. TGFbeta1-induced epithelial
      mesenchymal transition of SiHa cells was based on morphological and biochemical
      criteria; actin stress fiber formation, focal translocalization of integrin
      alphav, talin, and vinculin, fibronectin-based matrix assembly at the cell
      periphery, and translocalization and down-regulation of E-cadherin. TGFbeta1 also
      stimulated surface expression of integrin alphavbeta3 and FAK activation. Focal
      translocalization of integrin alphav preceded actin reorganization and
      fibronectin matrix assembly, and functional blocking of the integrin suppressed
      actin stress fiber formation. Furthermore, induction of actin reorganization and
      fibronectin matrix assembly by TGFbeta1 were shown to be mutually independent
      events. These changes were irreversible because 5 minutes pulse exposure to
      TGFbeta1 was sufficient to stimulate progress of actin reorganization and
      fibronectin matrix assembly. In further studies with raft culture, TGFbeta1 was
      found to stimulate invasion of SiHa cells into a type I collagen gel matrix. In
      conclusion, TGFbeta1 stimulated epithelial-mesenchymal transition of SiHa cells,
      indicating a positive role in the invasive transition of tumors.

PMID- 12234018
TI  - Choice of a primary care physician and its relationship to adherence among
      patients with diabetes.
AB  - OBJECTIVE: To investigate the association between selecting one's own primary
      care physician and adherence to treatment regimens as measured by patients'
      report of self-care behaviors and objective records of adherence to recommended
      prevention behaviors. STUDY DESIGN: A mail survey of physicians and their
      patients with diabetes. PATIENTS AND METHODS: Forty physicians and 1200 of their
      patients with diabetes (30 per physician) from 3 health centers of Kaiser
      Permanente in Northern California were surveyed. The questionnaires asked about
      satisfaction, treatment adherence, and physician behavior. Data from the Kaiser
      Permanente Diabetes Registry of Northern California were used to assess whether
      patients had undergone recommended prevention tests and screenings. RESULTS:
      Patients who chose their primary care physicians reported significantly greater
      adherence to their treatment regimens (P < .01) than those assigned to a primary
      care physician, and this relationship remained significant after controlling for
      possible confounding factors (eg, physician gender, patient gender, length of
      relationship). Objective records of prevention behaviors indicated that patients
      who chose their physicians were significantly more likely to have had a retinal
      exam (P < .02) and tests for total cholesterol (P < .001), high-density
      lipoprotein cholesterol (P < .03), and glycosylated hemoglobin (P < .02) during
      the past 12 months. CONCLUSIONS: The findings suggest that the manner in which
      patients are linked with primary care physicians is associated with patient
      behavior; therefore, HMOs might increase opportunities for patients to choose
      their doctors, while determining those factors that affect patient choice and why
      choice makes a difference.

PMID- 12234019
TI  - Methodology to improve data quality from chart review in the managed care
      setting.
AB  - BACKGROUND: Because inherent variability may exist in data collected by multiple
      reviewers or from potential difficulties with data abstraction tools, we
      developed a standardized method of evaluating interrater reliability (IRR) for
      clinical studies, HEDIS effectiveness of care measures, and onsite/medical record
      reviews. OBJECTIVE: To demonstrate the ability of our standardized methods of
      data collection and analysis of results to determine the extent of agreement
      between multiple reviewers; identify areas for improvement in data collection
      procedures; and improve data reliability. STUDY DESIGN: A prospective chart
      review with concurrent IRR. METHODS: A subsample of patient records included in
      the Highmark Blue Cross Blue Shield/Keystone Health Plan West basic medical
      review for each HEDIS measure was selected for the IRR study. An experienced
      nurse ("gold standard") conducted a blinded concurrent review of these records.
      Using the kappa statistic (kappa) we evaluated interobserver agreement between
      results of the onsite reviewers and the "gold standard" from 1997 through 2000.
      Revised data collection methods and enhanced reviewer training were incorporated
      for measures showing areas for rater improvement. RESULTS: Results across years
      showed excellent IRR for most measures; however, each year 1 or 2 measures showed
      areas for rater improvement (1997 Papanicolaou kappa = 0.50; 1998 well-child
      visits 3 to 6 years kappa = 0.37; 1999 comprehensive diabetes kappa = 0.73; high
      blood pressure kappa = 0.73). After reevaluating these measures, the results of
      the kappa showed excellent interrater agreement in subsequent years. CONCLUSIONS:
      Standardized methods of data collection and evaluation of IRR results provides
      health plans increased confidence in data collection, statistical analyses, and
      in reaching conclusions and deriving relevant recommendations.

PMID- 12234020
TI  - Pharmaceutical industry research and cost savings in community-acquired
      pneumonia.
AB  - OBJECTIVE: To provide financial justification for continuing pharmaceutical
      research in an environment that has met with increasing resistance from insurance
      carriers to paying for the care of patients enrolled in research studies. STUDY
      DESIGN: Matched case-control study of patients enrolled into inpatient community
      acquired pneumonia (CAP) pharmaceutical research protocols. PATIENTS AND METHODS:
      Case patients were enrolled into a CAP pharmaceutical research trial. Control
      patients were obtained from a prospective cohort study of CAP. Cases were matched
      to controls on the basis of age, sex, pneumonia severity index (PSI) grade, and
      comorbid illnesses as measured by the PSI and Acute Physiologic and Chronic
      Health Evaluation II (APACHE II) scoring systems. Financial data were obtained
      from hospital billing records. RESULTS: Twenty-five cases were identified and
      matched to appropriate controls. There was no statistically significant
      difference in mean PSI and APACHE II scores between cases and controls. There was
      a significant reduction in the total charges for hospital care of patients
      enrolled into a pharmaceutical industry trial ($6267 vs $9979; P = .03). As
      expected, the most dramatic reduction was in pharmacy charges ($642 vs $1797; P =
      .002), but there were trends toward lower charges in all cost subgroups.
      Interestingly, there was also a strong trend toward reduced length of hospital
      stay associated with enrollment in a pharmaceutical trial (4.5 vs 6.0 days; P =
      .06). CONCLUSION: Enrollment in a pharmaceutical research protocol results in
      significant cost savings in patients admitted to the hospital with CAP and may
      lead to earlier hospital discharge.

PMID- 12234021
TI  - Chiropractic and medical care costs of low back care: results from a practice
      based observational study.
AB  - OBJECTIVE: To compare the 1-year costs for patients treated for acute and chronic
      ambulatory low back pain by medical physicians and chiropractors. STUDY DESIGN:
      Prospective, practice-based observational study undertaken in 13 general medical
      practices and 51 chiropractic community-based clinics. PATIENTS AND METHODS: Of
      2872 study patients, 2263 had complete 1-year records of services. Service data,
      collected from billing records, chart audits, and provider questionnaires, were
      assigned relative value units that were converted into 1995 dollar costs.
      Prescription drug costs for medical patients were included. Patient data on
      health status, pain and disability, and socioeconomic characteristics were
      obtained from self-administered questionnaires. RESULTS: The direct office costs
      of treating both chiropractic and medical patients over a 1-year period were
      relatively small. Forty-three percent of chiropractic patients and 57% of medical
      patients incurred costs of less than $100. However, the mean costs associated
      with chiropractic patients ($214) were significantly higher than those for
      medical patients ($123), especially when compared with medical patients who were
      not referred for further treatment or evaluation ($103). Chiropractic patients
      had somewhat lower baseline levels of pain and disability than nonreferred
      medical patients, but the 2 groups were relatively similar on most patient
      characteristics. There also were no statistically significant differences in the
      improvements in pain and disability between these 2 groups of patients.
      CONCLUSION: The results of this study indicate that patients treated in
      chiropractic clinics incur higher costs over a 1-year period, but have about the
      same degree of relief as nonreferred patients treated in medical clinics.

PMID- 12234022
TI  - Health-related quality of life measurements and studies in rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a major cause of disability and
      impairment of health-related quality of life (HRQOL) in the United States.
      Increasingly, HRQOL assessments are becoming part of a package of materials
      reviewed by managed care providers in making formulary and reimbursement
      decisions. OBJECTIVE: To help managed care administrators understand how to
      interpret and apply the results of HRQOL assessment scales. METHODS: Several
      patient-reported instruments in common use in RA were reviewed, including the
      Health Assessment Questionnaire (HAQ), Modified HAQ, Arthritis Impact Measurement
      Scale, and the 36-item Short-Form Health Survey. RESULTS: These self-assessment
      scales help improve patient/physician communication and thus enable better
      treatment decision-making. The scales can also aid managed care administrators in
      evaluating the efficacy and the financial benefits of therapies. The HAQ was one
      scale that stood out as being short, easy to administer, and disease-specific for
      RA. CONCLUSIONS: Self-assessment reports, such as the HAQ, provide key data on
      disability and HRQOL from the patient's perspective. The information so gained
      enables the clinician to select the most cost-effective therapies and
      interventions that slow disease progression, maintain functional status, and
      improve HRQOL.

PMID- 12234023
TI  - Therapy-associated solid tumors.
AB  - As survival after a diagnosis of cancer improves, characterization of the late
      sequelae of treatment becomes critical. The development of second malignant
      neoplasms represents one of the most serious side effects of treatment with
      radiation and chemotherapy. Although secondary leukemia was the first reported
      carcinogenic effect resulting from cancer treatment, solid tumors now comprise
      the largest second tumor burden in some populations of survivors. It should be
      recognized, however, that solid cancers do not necessarily represent an adverse
      effect of therapy, but may also reflect the operation of shared etiologic
      factors, host determinants, gene-environment interactions, and other influences.
      Quantification of second cancer risk is important in terms of patient management,
      enabling clinicians to make informed decisions with regard to optimal treatment
      of the initial cancer, balancing efficacy against acute and chronic sequelae.
      This article focuses on selected highlights and recent developments in treatment
      associated solid malignancies, with emphasis on radiotherapy and chemotherapy in
      adults, and summarizes areas for future research. Although cancer therapy
      represents a double-edged sword, it should always be recognized that it is
      advances in treatment that are largely responsible for the tremendous improvement
      in patient survival. Thus, the benefit derived from many cancer therapies far
      outweighs any risk of developing a second cancer.

PMID- 12234024
TI  - Predictive factors for response to chemotherapy in advanced breast cancer.
AB  - Most breast cancer patients receive chemotherapy at some phase of their illness
      but only about half of them benefit from it. Identifying the factors predicting
      response to chemotherapy would also assist the clinician in selection of
      appropriate patients for chemotherapy, thus saving others from unnecessary
      exposure to toxic agents. At the present time, there is no tumour biological
      factor available for clinical use in the prediction of chemotherapy response in
      advanced breast cancer apart from oestrogen receptor status, which predicts
      response to hormonal therapy, or the HER2 receptor, which predicts response to
      trastuzumab. Interestingly, they both are also targets for those therapies.
      Several groups have tried to find such predictive factors for chemotherapy in
      advanced breast cancer but the results are so far disappointing. This review
      collects the rapidly expanding data published so far on the predictive value of
      tumour biological factors for chemotherapy response in advanced breast cancer. In
      conclusion, none of them is yet good enough for clinical use in advanced breast
      cancer.

PMID- 12234025
TI  - Pathogenesis of cognitive decline following therapeutic irradiation for head and
      neck tumors.
AB  - Cognitive decline is a significant but largely unrecognized sequela following
      irradiation for several head and neck tumors, particularly cancer of the
      nasopharynx and paranasal sinuses. In this article the cellular mechanisms of
      radiation-induced vascular damage in the temporal lobe and its effects on the
      medial temporal lobe memory systems are described. Recognition of the mechanisms
      and site of the injury should permit the use of treatment planning systems, such
      as 3-dimensional (3-D) conformal and intensity-modulated radiotherapy (IMRT)
      techniques, to spare large volumes of the temporal lobe from receiving a high
      dose. Furthermore, the emerging concepts of vascular irradiation damage as an
      inflammatory fibroproliferative response to endothelial injury may permit the
      application of measures directed at inhibiting the expression of proinflammatory
      genes and thus mitigate the inflammatory response. Moreover, comorbid factors
      such as hypertension, diabetes, lipidemia, obesity and smoking are known to
      promote atherogenesis and therefore may exacerbate radiation-induced vascular
      damage. Control of these factors may also reduce the incidence and severity of
      this sequela.

PMID- 12234026
TI  - Is LRIG1 a tumour suppressor gene at chromosome 3p14.3?
AB  - The LRIG1 gene (formerly LIG-1), recently cloned by us, displays structural
      similarities to the Drosophila Kek I gene. Kek I encodes a cell surface protein,
      Kekkon-1, which inhibits epidermal growth factor receptor-mediated signalling. We
      localized the LRIG1 gene to chromosome band 3p14.3, a region known to be deleted
      in various human cancers. In the present study LRIG1 gene expression was examined
      in different tumour cell lines and corresponding normal tissues by real-time RT
      PCR. In many tumour cell lines, LRIG1 expression appeared absent or was down
      regulated compared to corresponding normal tissues. The results are consistent
      with LRIG1 being a tumour suppressor gene in humans. However, further studies are
      justified to elucidate the explicit role of LRIG1 as a negative regulator of
      oncogenesis.

PMID- 12234027
TI  - Nm23 gene product expression in invasive breast cancer--immunohistochemical
      analysis and clinicopathological correlation.
AB  - The nm23 gene/protein is a putative metastatic suppressor identified a decade ago
      in a melanoma cell line. A number of laboratory, clinical and pathological
      studies have been carried out to define its real biological and biochemical
      function as a step in a complex metastatic process. In our study we examined the
      significance of nm23 expression in 164 breast cancer patients, aged 35 to 74
      years, in comparison to other parameters such as age, menopausal status,
      histological grade, tumor size, lymph node status, and hormone receptor status.
      Overall survival (OS) and disease-free survival (DFS) were analyzed. The median
      follow-up was 84 months. Significant changes in OS were found for tumor size,
      nodal involvement and histological grade but there was no convincing correlation
      with nm23 expression. When patients were stratified according to nm23 expression,
      it was shown that overall survival in nm23-positive patients was no longer than
      that in nm23 negative patients. It was also shown that patients who were lymph
      node negative and older than 50 years had longer OS than nm23-negative patients.
      A statistical analysis shows that there is a correlation between axillary node
      status and nm23 expression (p = 0.018) as well as between patients' ages and nm23
      expression (p = 0.043). There was no statistically significant correlation
      between nm23 expression, lymph node status and their combination on DFS.

PMID- 12234028
TI  - Does famotidine enhance tumor infiltrating lymphocytes in breast cancer? Results
      of a randomized prospective pilot study.
AB  - Thirty patients with breast cancer were prospectively randomized into case and
      control groups receiving 40 mg famotidine preoperatively for 10-14 days and
      routine premedication, respectively. Surgical specimens were evaluated
      objectively for tumor infiltrating lymphocytes in the center and in the periphery
      of the tumor along with evaluation of metastatic lymph nodes for reactive
      changes. Ten famotidine-treated cases (67%) showed significant lymphocytic
      infiltration in the center compared to 4 controls (27%) (p = 0.03). Eleven cases
      (77%) had significant lymphocytic infiltration in the periphery (p = 0.03)
      compared to 5 controls (33%). Considering both sites, lymphocytic response was
      significant in 9 (60%) cases as opposed to only 3 (20%) controls (p = 0.03). This
      response did not correlate with the stage, grade of tumor or menopausal status of
      patients in either group. Seventy-eight percent (78%) of the cases showed
      significant reactive changes in the metastatic lymph nodes as compared to 22% in
      controls (p < 0.01). This study suggests that famotidine enhances tumor
      infiltrating lymphocytes in breast cancer and might have potential as an
      immunomodulator. A larger confirmatory study is suggested.

PMID- 12234029
TI  - Lack of ErbB-2 oncogene product overexpression in soft tissue sarcomas.
AB  - The c-erbB-2 gene and its products (also designated HER-2 and c-neu) encode for a
      185-kd transmembrane glycoprotein with intracellular tyrosine kinase activity. c
      erbB-2 belongs to the epidermal growth factor receptor family, of which there are
      four known members, and has molecular homology to the epidermal growth factor
      receptor. It seems that this family is critical in control of growth,
      differentiation, and mobility of many normal and transformed epithelial cell
      types. We have looked for overexpression of c-erbB-2 gene product in paraffin
      embedded material from 230 cases of soft tissue sarcoma, in order to establish a
      possible new prognostic marker and a potentially new treatment option. In all the
      cases, irrespective of the sarcoma histological type, the immunostaining for erbB
      2 was negative. Applications of erbB-2 for prognostication as well as the option
      of receptor targeting by trastuzumab monoclonal antibodies were aborted.

PMID- 12234030
TI  - Cosmetic outcome and breast morbidity in breast-conserving treatment--results
      from the Danish DBCG-82TM national randomized trial in breast cancer.
AB  - A total of 266 recurrence-free breast cancer patients from the randomized DBCG
      82TM breast conservation trial were called in for a follow-up investigation to
      study the impact of surgical and radiation treatment factors on the cosmetic and
      functional outcome after breast conservation. The patients were interviewed and
      examined after a median follow-up time of 6.6 years, and 194 of them (73%)
      regarded the cosmetic result as excellent or good. Morbidity assessments showed
      that breast fibrosis, skin telangiectasia, and breast retraction were
      significantly associated with a less satisfactory cosmetic result. On univariate
      analysis, it was found that treatment with a direct anterior electron field
      produced more morbidity and inferior cosmetic outcomes compared with tangential
      photon treatment, while increasing breast size was associated with increased
      breast retraction and breast fibrosis. Treatment characteristics that emerged as
      independent prognostic factors of a poor cosmetic outcome on multivariate
      analysis were the use of a direct anterior electron field (OR = 2.15, CI 1.25
      3.70) and adjuvant systemic therapy (OR = 2.13, 1.22-3.71). A significant but
      relatively low level of concordance was found between the patients' and the
      clinician's evaluations of cosmetic results but self-assessments of breast
      morbidity and psychological distress were significantly related to the observed
      treatment-induced side effects after breast-conserving treatment, indicating that
      subjective perceptions and observations as reported by the patients are relevant
      for the identification of treatment factors that impact on normal tissue
      reactions.

PMID- 12234031
TI  - The Finnish Cancer Registry as follow-up source of a large trial cohort--accuracy
      and delay.
AB  - We evaluated the accuracy and time to reporting of cancer diagnoses obtained
      through the Finnish Cancer Registry (FCR) for the Alpha-Tocopherol Beta-Carotene
      Cancer Prevention (ATBC) Study in 1985-1997. In the ATBC Study suspect neoplasms
      were centrally reviewed through medical records and pathology specimens. The FCR
      data were compared against the reviewed data for 3600 cancers of eight sites. For
      most sites, 95% of the cases were reported to the FCR within 0.9 years with
      longer delays for lung and pancreatic cancers. Ninety-six percent of all FCR
      cases received the same primary site diagnosis in the ATBC review, and in 1.4% no
      malignancy was found. Conversely, 97% of cancers ascertained in the ATBC review
      had the same primary site in the FCR and 0.8% were unknown to the Registry. The
      accuracy of the FCR data is high but the delay in case notification should be
      considered in epidemiological studies.

PMID- 12234032
TI  - Dietary habits and lung cancer risk among Polish women.
AB  - The purpose of this case-control study was to examine the effect of usual diet,
      in relation to other risk factors, on the risk of different histologic types of
      lung cancer in women. A total of 242 women with histologically confirmed primary
      lung cancer and 352 healthy controls were enrolled in a study conducted in Cracow
      between 1991 and 1997. A multivariate analysis showed that frequent consumption
      of carrots (at least five times a week) significantly lowered the risk of lung
      cancer. The protective effects of carrots were statistically significant for
      squamous cell carcinoma, small cell carcinoma and adenocarcinoma. It was found
      that daily consumption of other vegetables had a significant protective effect
      against squamous cell carcinoma, and for all histologic types combined.
      Furthermore, a significantly reduced risk was observed in women who consumed
      margarine (at least three times a week). This effect was observed for all cell
      types. The results also suggest that frequent consumption of carrots and frequent
      consumption of margarine can have a protective influence against lung cancer
      irrespective of the number of cigarettes smoked and the amount of vodka drunk.

PMID- 12234033
TI  - Intensity-modulated radiotherapy of sacral chordoma--a case report and a
      comparison with stereotactic conformal radiotherapy.
AB  - In a case of partially resected sacral chordoma, the planning target volume (PTV)
      received 60 Gy and the gross target volume (GTV) 72 Gy using inversely planned,
      intensity-modulated, radiation therapy (IMRT). IMRT was compared with 3D
      conformal radiotherapy (CRT). With IMRT, it was found that dose distribution is
      more homogeneous within the PTV outside the GTV and allows simultaneous dose
      escalation within the GTV. The volume of bowel receiving a dose higher than 40 Gy
      was reduced from 400 cc with CRT to 220 cc with IMRT. If particle therapy is not
      available, IMRT seems to be a promising alternative in the treatment of sacral
      chordomas.

PMID- 12234034
TI  - Direct and indirect cost of general aviation crashes.
AB  - BACKGROUND: There have been few well-designed studies which estimate the costs
      inflicted on society from injuries, fatalities, and property damage caused by
      aviation crashes. Furthermore, indirect cost estimates from the human capital
      (HC) approach tend to be substantially smaller than those obtained from the
      willingness-to-pay (WTP) approach. OBJECTIVES: To estimate the direct and
      indirect costs of general aviation crashes in New Zealand, and to contrast the HC
      and WTP approaches used to estimate indirect costs. METHODS: The incidence,
      morbidity, and mortality from aviation crashes between 1988 and 1997 were
      estimated from national health and aviation records. Direct costs included
      medical treatment, damage to aircraft and property, and the cost of crash
      investigation. For the HC approach, we valued losses to society as the value of
      lost production from both employed work and household activity. For the WTP
      approach, we used the Land Transport Safety Authority's estimated values of
      society's willingness to pay to avoid a fatality or injury. RESULTS: The annual
      average direct cost of aviation crashes was $9.1 m (range: $8.0 m to $11.4 m).
      The annual average indirect cost using the HC approach was $13.6 m ($5.6 m to
      $32.2 m). Using the WTP approach the annual average indirect costs was $49.3 m
      ($20.6 m to $106.5 m). Indirect costs from premature deaths were the key cost
      drivers. A sensitivity analysis showed that these values were relatively robust
      to changes in parameters. CONCLUSION: The annual average cost of general aviation
      crashes in New Zealand was between $22.6 m and $58.4 m. Indirect costs using the
      WTP approach were 3.5 times greater than those estimated using the HC approach.

PMID- 12234035
TI  - Resting energy expenditure of rats acclimated to hypergravity.
AB  - BACKGROUND: The use of centrifugation at 1 G has been advocated as a control
      condition during spaceflight and as a countermeasure to compensate for the
      adverse effects of spaceflight. Rodents are the primary animal model for the
      study of the effects of spaceflight and will be used in the evaluation of
      centrifugation as a countermeasure and means of control at 1 G during flight.
      HYPOTHESIS: The present study was designed to assess whether resting energy
      expenditure (EER) of male rats was increased in relation to the magnitude of the
      level of gravity to which the animals were exposed. The influence of body mass
      and age on resting energy expenditure (EER) of male rats (n = 42, age 40-400 d)
      was determined following 2 wk of acclimation to 1, 2.3, or 4.1 G. Hypergravity
      environments were created by centrifugation. Measurements were made at the
      gravity level to which the animal was acclimated and during the lights-on period.
      RESULTS: In rats matched for body mass (approximately 400 g), mean O2 consumption
      and CO2 production were higher (18% and 27%, respectively) in the 2.3- and 4.1 -G
      groups than controls. Mean respiratory exchange ratio (RER) increased from 0.80
      to 0.87. EER was increased from 47 +/- 0.1 kcal x d(-1) at 1 G, to 57 +/- 1.5 and
      58 +/- 2.2 kcal x d(-1) at 2.3 and 4.1 G, respectively. There was no difference
      in EER between the hypergravity groups. When age differences were considered, EER
      (kcal x kg(-1) x d(-1)) with increased gravity was 40% higher than at 1 G. The
      increase in EER was not proportional over gravity levels. CONCLUSION: Acclimation
      of rats to hypergravity increases their EER, dependent on body mass and age, and
      may alter substrate metabolism. The increase in EER was not related to the level
      of gravity increase.

PMID- 12234036
TI  - Spatial reference and standing posture during high-speed Coriolis stimulation.
AB  - BACKGROUND: In a previous study, we found that sensation, gaze, and posture
      during Coriolis stimulation differ considerably between vision and nonvision
      conditions during rotations at 60 degrees x s(-1). To determine the validity of
      these findings at higher velocities, we compared standing postures during
      Coriolis stimulation up to 150 degrees x s(-1) between vision and nonvision
      conditions. METHODS: The 19 subjects underwent 5-min rotation tests at 50 to 150
      degrees x s(-1). While standing on a force platform attached to a rotating
      device, each subject tilted his or her head and then returned it to upright,
      first with the eyes covered, then with eyes open. Six subjects were re-examined 5
      d later after 4 consecutive days of 20-min rotations with their eyes open. We
      assessed success and failure to stand and recorded the center of pressure during
      rotation. RESULTS: Although success rates (number of successes/19) differed
      between vision and nonvision conditions at 50 degrees x s(-1) (94.7% vs. 57.9%),
      they steeply decreased as rotation velocity increased and showed no difference at
      70 degrees x s(-1) and faster velocities. After the 4-d exposure, however,
      subjects could stand at higher velocities particularly under the vision
      condition. A patient with bilateral labyrinthine loss, being examined for
      reference, could stand at 110 degrees x s(-1) even with the eyes covered.
      CONCLUSIONS: Untrained subjects frequently fell during high-speed Coriolis
      stimulation, apparently because vision was insufficient to provide a spatial
      reference frame from the stationary surroundings. Following rotation training
      with their eyes open, subjects appeared more able to use the visual reference
      frame and falls were reduced.

PMID- 12234037
TI  - Moderate exercise after altitude exposure fails to induce decompression sickness.
AB  - INTRODUCTION: The objective of this study was to determine the effect of exercise
      after altitude exposure (post-exposure exercise) on subsequent altitude
      decompression sickness (DCS) incidence. Existing USAF prohibition of exercise
      following altitude chamber training exposures and interest from operational
      personnel prompted our evaluation of post-exposure exercise as a DCS-inducing
      stressor. METHODS: After a 1-h resting preoxygenation, 67 subjects were exposed
      to 30,000 ft for 2-h while performing mild, upper body exercise. The subjects
      were monitored for venous gas emboli (VGE) with an echo-imaging system and
      observed for signs and symptoms of DCS. Subjects without DCS (n = 31) or with DCS
      which resolved during recompression (n = 29) were randomly assigned to post
      exposure rest (control, n = 29) or moderate exercise (50% of peak oxygen uptake,
      dual-cycle ergometry; n = 31) and both groups were monitored for delayed or
      recurring DCS. RESULTS: The altitude exposure resulted in 48.3% DCS in the 60
      volunteers serving as test or control subjects. Of 31 subjects assigned to the
      post-exposure exercise group, 15 had developed DCS which resolved during descent.
      No cases of DCS were observed or reported during or following post-exposure
      exercise. CONCLUSION: The results show that moderate exercise after exposure did
      not result in either delayed-onset or recurring DCS.

PMID- 12234039
TI  - The value of experienced medical personnel during the investigation of general
      aviation accidents.
AB  - A multidisciplinary approach to accident investigation is routine in commercial
      aircraft accidents. A medical team is usually assigned to assist with the
      investigation. As far as general aviation accidents are concerned, in a majority
      of cases, these resources are not available to the investigator-in-charge. We
      describe a general aviation accident to illustrate the scope of medical and human
      factors information that can be determined by professionals who assist the
      authorities with the investigation. Following the example, we suggest a method of
      identifying available expertise. Voluntary contributions from trained specialists
      need to be utilized to assist general aviation accident investigators and help
      promote aviation safety.

PMID- 12234038
TI  - Impact of influenza vaccination on civilian aircrew illness and absenteeism.
AB  - BACKGROUND: Approximately 10% of the general population worldwide acquires
      influenza infection every year. Airline crews run a particularly high risk of
      contracting influenza and influenza-like viruses because they come in contact
      with hundreds of potentially infected individuals every day. Respiratory diseases
      are the most frequent cause of absenteeism among flight crews in airline
      companies. Several studies have shown the efficacy of influenza vaccination in
      the workplace of healthy, working adults leading to increased productivity and
      lower absenteeism. We conducted a double blind, randomized, placebo-controlled
      study on flight crews of an airline company in order to determine the safety and
      efficacy of a trivalent inactivated influenza vaccine in reducing illness and
      absences from work. METHODS: The 813 healthy members of a Brazilian airline
      company were randomly assigned to receive injections of either an influenza
      vaccine or a placebo, with a follow-up period of 7 mo after vaccination. Primary
      outcomes included influenza-like illness episodes and absenteeism from work due
      to such episodes. RESULTS: Demographic characteristics were similar in the two
      groups. No significant side-effects occurred in either group. Compared to the
      placebo group, individuals receiving the vaccine showed 39.5% fewer episodes of
      flu-like illness (p < 0.001) and 26% fewer days of work lost (p = 0.03). The
      vaccinated group developed 33% fewer episodes of any severe flu-like illness (p <
      0.01). CONCLUSION: The data indicates that influenza vaccination is safe in
      airline flight crews and may produce health-related benefits including reduced
      absenteeism.

PMID- 12234040
TI  - Automated fault-management in a simulated spaceflight micro-world.
AB  - BACKGROUND: As human spaceflight missions extend in duration and distance from
      Earth, a self-sufficient crew will bear far greater onboard responsibility and
      authority for mission success. This will increase the need for automated fault
      management (FM). Human factors issues in the use of such systems include
      maintenance of cognitive skill, situational awareness (SA), trust in automation,
      and workload. This study examine the human performance consequences of operator
      use of intelligent FM support in interaction with an autonomous, space-related,
      atmospheric control system. METHODS: An expert system representing a model-base
      reasoning agent supported operators at a low level of automation (LOA) by a
      computerized fault finding guide, at a medium LOA by an automated diagnosis and
      recovery advisory, and at a high LOA by automate diagnosis and recovery
      implementation, subject to operator approval or veto. Ten percent of the
      experimental trials involved complete failure of FM support. RESULTS: Benefits of
      automation were reflected in more accurate diagnoses, shorter fault
      identification time, and reduced subjective operator workload. Unexpectedly,
      fault identification times deteriorated more at the medium than at the high LOA
      during automation failure. Analyses of information sampling behavior showed that
      offloading operators from recovery implementation during reliable automation
      enabled operators at high LOA to engage in fault assessment activities
      CONCLUSIONS: The potential threat to SA imposed by high-level automation, in
      which decision advisories are automatically generated, need not inevitably be
      counteracted by choosing a lower LOA. Instead, freeing operator cognitive
      resources by automatic implementation of recover plans at a higher LOA can
      promote better fault comprehension, so long as the automation interface is
      designed to support efficient information sampling.

PMID- 12234041
TI  - Acute mountain sickness, dehydration, and bicarbonate clearance: preliminary
      field data from the Nepal Himalaya.
AB  - BACKGROUND: In 1999, Basnyat et al. published preliminary data demonstrating an
      inverse correlation between hydration status and acute mountain sickness during
      an epidemiological study performed in the vicinity of Mount Everest. To expand on
      these findings, we have re turned to the Langtang area of the Nepal Himalaya to
      perform more specific studies of altitude illness related to dehydration and
      hypoxemia using urine studies, pulse oximetry, and physical examination.
      HYPOTHESIS: Dehydration will incite physiological changes aimed at the
      preservation of vascular volume homeostasis characterized by the production of
      sodium and water sparing hormones. As sodium is reabsorbed in the kidney,
      bicarbonate anion is also reabsorbed resulting in insufficient bicarbonate anion
      excretion by the kidney leading to an incomplete compensation for altitude
      induced hypocapnic alkalosis and the development of clinical disease. METHODS:
      Estimates of intravascular volume (urine specific gravity), oxygen saturation
      (pulse oximetry), urinary bi carbonate excretion (urine pH), and AMS (Lake Louise
      Score) were collected from Hindu pilgrims at 4243 m during an annual sacred
      festival at Lake Gosinkunda. RESULTS: Worsening altitude illness approx imated by
      increasing Lake Louise Score was associated with increasing urine specific
      gravity (p = 0.043), decreasing oxygen saturation (p = 0.020), and decreasing
      urine pH (p = 0.040) after rapid ascent to 4243 m. CONCLUSIONS: Worsening
      altitude illness, indicated by increasing Lake Louise score, was associated with
      increasing measures of dehydration, hypoxemia, and urine acidity.

PMID- 12234042
TI  - Plasma volume by Evans blue: effects of eating and comparison with other methods
      at altitude.
AB  - HYPOTHESIS: Measurements of plasma volume (PV) and its changes (delta%PV) by
      Evans blue (EB) dye are presumed to be valid only in fasting subjects. In
      addition, delta%PVEB with acute altitude exposure has not been compared with
      other methods employing the concentration or dilution of naturally occurring
      blood (hematocrit (Hct), hemoglobin (Hb)) and plasma (density, proteins)
      components, but should be similar if capillary permeability and the sampled
      vein/whole body Hct ratio remain unchanged. METHODS: PVEB was determined in six
      subjects while fasting or eating on different days, with injection and sampling
      in the same arm, 4-h extrapolation to time zero and correcting readings with the
      620-740 A method. For 93 experiments at altitude, delta%PVEB was obtained
      similarly from a 3-h extrapolation near the end of a 12-h chamber exposure to 426
      mm Hg (-4,880 m =16,000 ft) and at the same time on the preceding control day.
      RESULTS: Mean PVEB with and without eating was not significantly different (SE of
      absolute difference = +/- 2.8%). The EB decay curves had significantly more
      scatter with eating than fasting. The fasting vs. non-fasting values for the
      single 20-min post-injection point also gave a close comparison (r = +0.97). At
      altitude the loss in PV measured with EB was significantly greater (delta%PVEB = 
      6.3%) than losses estimated from Hct-Hb (-2.9%), plasma protein (-3.7%), and
      plasma density (-3.9%). The expected larger PV loss in subjects tolerant to
      altitude sickness compared with intolerant ones was most clearly shown by
      delta%PVEB (8.8%). CONCLUSIONS: Obtaining more samples can offset reproducibility
      lost by eating. The delta%PVEB were largest and nearest to values previously
      reported at altitude, perhaps because the single baseline and altitude samples
      utilized by the other methods are more sensitive to subtle, transient
      fluctuations in body water and vasomotor tone associated with apprehension,
      vomiting, fluid intake, and regional vasodilation and constriction.

PMID- 12234043
TI  - Performance of advanced trauma life support procedures in microgravity.
AB  - BACKGROUND: Medical operations on the International Space Station will emphasize
      the stabilization and transport of critically injured personnel and so will need
      to be capable of advanced trauma life support (ATLS). METHODS: We evaluated the
      ATLS invasive procedures in the microgravity environment of parabolic flight
      using a porcine animal model. Included in the procedures evaluated were
      artificial ventilation, intravenous infusion, laceration closure, tracheostomy,
      Foley catheter drainage, chest tube insertion, peritoneal lavage, and the use of
      telemedicine methods for procedural direction. RESULTS: Artificial ventilation
      was performed and appeared to be unaltered from the 1-G environment. Intravenous
      infusion, laceration closure, percutaneous dilational tracheostomy, and Foley
      catheter drainage were achieved without difficulty. Chest tube insertion and
      drainage were performed with no more difficulty than in the 1-G environment due
      to the ability to restrain patient, operator and supplies. A Heimlich valve and
      Sorenson drainage system were both used to provide for chest tube drainage
      collection with minimal equipment, without the risk of atmospheric contamination,
      and with the capability to auto-transfuse blood drained from a hemothorax. The
      use of telemedicine in chest tube insertion was demonstrated to be useful and
      feasible. Peritoneal lavage using a percutaneous technique, although requiring
      less training to perform, was found to be dangerous in weightlessness due to the
      additional pressure of the bowel on the anterior abdominal wall creating a high
      risk of bowel perforation. CONCLUSIONS: The performance of ATLS procedures in
      microgravity appears to be feasible with the exception of diagnostic peritoneal
      lavage. Minor modifications to equipment and techniques are required in
      microgravity to effect surgical drainage in the presence of altered fluid
      dynamics, to prevent atmospheric contamination, and to provide for the restraint
      requirements. A parabolic simulation system was developed for equipment and
      procedure verification, physiological research, and possible crew medical officer
      training in the future.

PMID- 12234044
TI  - Ergonomic assessment of a helicopter crew seat: the HH-60G flight engineer
      position.
AB  - BACKGROUND: Reports of back pain among military helicopter aircrew have appeared
      in the aviation medicine literature since the 1960s. Likewise, anecdotal
      complaints of back and neck pain among HH-60G crewmembers have long persisted.
      The purpose of the present study was to identify specific work factors that could
      contribute to increased musculoskeletal discomfort among HH-60G flight engineers
      and gunners, and to recommend actions to remedy observed workplace deficiencies.
      METHODS: The physical dimensions of the HH-60G flight engineer/gunner workstation
      were measured, and the activities and work postures of a flight engineer and
      gunner were observed and photographed during flight. Measurements of crew station
      dimensions were compared against anthropometric data for U.S. Air Force flying
      personnel to estimate of the percentage of the crew accommodated by the available
      work area. RESULTS: Results show that the current crew seat configuration forces
      the vast majority of HH-60G flight engineers/gunners to assume a variety of
      awkward neck, back, and lower extremity postures during flight. Based on existing
      epidemiological evidence, it is highly plausible that maintaining these postures
      for sustained periods of time could lead to increased musculoskeletal fatigue and
      discomfort in this population. CONCLUSIONS: Two major deficiencies that can be
      addressed to improve posture and reduce musculoskeletal stress among HH-60G
      flight engineers and gunners involve the design of the crew seat backrest, and
      the lack of space between the seat and the side of the aircraft for the legs and
      feet. Specific recommendations for crew seat design are provided.

PMID- 12234045
TI  - Pilot cerebral oxygen status during air-to-air combat maneuvering.
AB  - BACKGROUND: Successful monitoring of in-flight cerebral oxygen status (COS;
      cerebral hemoglobin concentration changes and oxygenation changes under dynamic
      flight conditions) was recently achieved using near-infrared spectroscopy (NIRS).
      In this study, we examined the effects of air-to-air combat maneuvering on COS.
      METHOD: Six F-15 fighter pilots performed 2-vs.-1 air-to-air combat one to three
      times in each of eight sorties. We took continuous measurements of the pilots' in
      flight COS using a commercial NIRS system. We measured the direct effects of G
      forces on COS as evidenced by relative concentrations of oxy- and deoxy
      hemoglobin. RESULTS: With respect to the G-levels reached during air combat
      maneuvering (Gz range of -0.4 to + 9.5), oxyhemoglobin concentration (O2Hb) and
      tissue oxygenation index (TOI, the ratio of oxygenated to total tissue
      hemoglobin) decreased with increasing G-forces during aerial combat maneuver
      (ACM). Maximum changes in relative O2Hb ranged from -4.2 to -26 micromol x L(-1).
      Subjects' experience as measured by total fighter time was an independent
      determinant of the magnitude of decrease in relative oxygenation. CONCLUSIONS: 1.
      Pilots' COS declined with dynamic G-forces experienced under aerial combat
      conditions. 2. Fighter pilots with more flying hours maintained a higher cerebral
      oxygen level at the same level of G-forces than pilots with less flying time. 3.
      NIRS technology in the form of the NIRO-300G has matured for continuous
      monitoring of in-flight cerebral oxygen status under vigorous field conditions.

PMID- 12234046
TI  - Percutaneous aspiration of fluid for management of peritonitis in space.
AB  - BACKGROUND: As a medical emergency that can affect even well-screened, healthy
      individuals, peritonitis developing during a long-duration space exploration
      mission may dictate deviation from traditional clinical practice due to the
      absence of otherwise indicated surgical capabilities. Medical management can
      treat many intra-abdominal processes, but treatment failures are inevitable. In
      these circumstances, percutaneous aspiration under sonographic guidance could
      provide a "rescue" strategy. HYPOTHESIS: Sonographically guided percutaneous
      aspiration of intra-peritoneal fluid can be performed in microgravity. METHODS:
      Investigations were conducted in the microgravity environment of NASA's KC-135
      research aircraft (0 G). The subjects were anesthetized female Yorkshire pigs
      weighing 50 kg. The procedures were rehearsed in a terrestrial animal lab (1 G).
      Colored saline (500 mL) was introduced through an intra-peritoneal catheter
      during flight. A high-definition ultrasound system (HDI-5000, ATL, Bothell, WA)
      was used to guide a 16-gauge needle into the peritoneal cavity to aspirate fluid.
      RESULTS: Intra-peritoneal fluid collections were easily identified, distinct from
      surrounding viscera, and on occasion became more obvious during weightless
      conditions. Subjectively, with adequate restraint of the subject and operators,
      the procedure was no more demanding than during the 1-G rehearsals. CONCLUSIONS:
      Sonographically guided percutaneous aspiration of intra-peritoneal fluid
      collections is feasible in weightlessness. Treatment of intra-abdominal
      inflammatory conditions in spaceflight might rely on pharmacological options,
      backed by sonographically guided percutaneous aspiration for the "rescue" of
      treatment failures. While this risk mitigation strategy cannot guarantee success,
      it may be the most practical option given severe resource limitations.

PMID- 12234047
TI  - Avulsion of the triceps tendon during acceleration stress.
AB  - The authors present a rare case of triceps tendon avulsion associated with +5 G
      force and muscle straining. Although failure of musculoskeletal system, mainly
      the cervical spine, secondary to high-G exposure has been reported, this is the
      first report they have found of a triceps tendon avulsion. Furthermore, unlike
      other traumatic triceps avulsions reported, the pilot involved had no known
      predisposing factors. Awareness of the possibility of such an injury must be
      maintained when a pilot of high performance aircraft presents with elbow pain.

PMID- 12234048
TI  - Safety of air travel following acute myocardial infarction.

PMID- 12234049
TI  - Safety of air travel following acute myocardial infarction.

PMID- 12234050
TI  - Hearing loss from cockpit noise in motor gliders.

PMID- 12234051
TI  - Control reversal using helmet-mounted displays.

PMID- 12234052
TI  - Hubertus Strughold Award. Earl H. Wood, M.D., Ph.D.

PMID- 12234053
TI  - The Young Investigator Award. Sophie Lelande, B.Sc., M.S.

PMID- 12234054
TI  - Nitric oxide-induced inhibition of mouse paw edema: involvement of soluble
      guanylate cyclase and potassium channels.
AB  - OBJECTIVE AND DESIGN: To investigate the effect of nitric oxide (NO) donors on
      inflammatory mouse paw edema (MPE). MATERIALS AND METHODS: Mice previously
      treated with sodium nitroprusside (SNP; 1.5, 5 and 10 micromol/kg) or S-nitroso-N
      acetyl-DL-penicillamine (SNAP; 7, 14 and 28 micromol/kg) were injected with
      inflammatory mediators in the paw. Paw edema, myeloperoxidase activity and
      vascular dye leakage were measured. RESULTS: Pre-treatment with SNP and SNAP (4 h
      or 12 h) reduced (approximately 50%) MPE induced by carrageenan, dextran sulfate,
      bradykinin and histamine but not by serotonin. Pre-treatment with SNP also
      inhibited carrageenan-induced increases in myeloperoxidase activity and vascular
      dye leakage. Methylene blue blocked the SNP-induced reduction in MPE when
      injected 30 min before or 2 h after SNP, but not 4 or 6 h after the NO donor.
      Tetraethylammonium blocked the SNP-induced reduction in MPE if injected 30 min
      before or 2, 4 or 6 h after SNP. CONCLUSIONS: NO donors have a long-lasting anti
      inflammatory effect in MPE, which involves guanylate cyclase and
      tetraethylammonium-sensitive potassium channels.

PMID- 12234055
TI  - Role of prostaglandins and nitric oxide in gastric damage induced by metamizol in
      rats.
AB  - OBJECTIVE AND DESIGN: In addition to the depletion of prostaglandins (PGs),
      oxygen free radicals generation and nitrogen species haven been implicated in non
      steroidal anti-inflammatory drugs (NSAIDs)-induced gastric injury. The aim of the
      present study was to examine changes in PGE2 generation and its relationship with
      proinflammatory parameters and nitric oxide (NO) production in the comparative
      pathogenesis of gastric injury induced by metamizol vs. diclofenac, NSAIDs that
      present different gastric tolerability and cyclooxygenase (COX) inhibition
      profiles. MATERIAL: Studies were performed in Wistar-Han rats. TREATMENTS:
      Metamizol (120, 500 and 1,000 mg/kg body weight) and diclofenac (50 mg/kg body
      weight) were given by oral administration. METHODS: Determinations were made of
      macroscopic and histological evaluation of gastric mucosal injury, gastric
      prostaglandin synthesis (PGE2 levels), myeloperoxidase activity (MPO), tumor
      necrosis factor-alpha levels (TNF-a), cyclic guanosine monophosphate (cGMP),
      nitric oxide synthase activity (NOS) and NOS mRNA expression. RESULTS: Metamizol,
      only at the highest doses assayed, provoked weak lesions in the gastric mucosa.
      To the contrary, diclofenac treatment presented the highest grade of lesion. All
      treatments decreased PGE2 gastric generation. Treatment of the animals with
      metamizol neither modified the MPO activity nor TNF-alpha levels. In contrast,
      statistically significant increases in both parameters were observed after
      diclofenac administration. cGMP levels were not influenced with diclofenac
      treatment, nevertheless metamizol reduced the nucleotide levels, which was
      accompanied by an inhibition of constitutive NOS (cNOS) activity without
      modifying the mRNA expression of the enzyme. CONCLUSIONS: In addition to
      inhibition of PG synthesis, damage induced by metamizol was associated with an
      inhibition of the NO/cGMP pathway and cNOS activity. In contrast, diclofenac
      induced gastric damage was associated with an increase of the inflammatory
      response.

PMID- 12234056
TI  - Release of algesic substances in human experimental muscle pain.
AB  - OBJECTIVE: We employed the 'delayed onset of muscle soreness' (DOMS) and the
      'hypertonic saline' muscle pain models in combination with muscle microdialysis
      to evaluate the role of potentially algesic substances (lactate, glutamate,
      prostaglandin E2 (PGE2), nitric oxide (NO) and substance P (SP)) in the
      development of human muscle pain. METHODS: DOMS was induced by 2 sets of 50
      concentric/eccentric contractions of the calf muscles 24 h before the start of
      microdialysis. During microdialysis pain was stimulated through calf muscle
      contractions (dorsal and plantar flexions of the foot). Hypertonic saline was
      injected into the biceps muscle (5 x 200 microl 5.8% NaCl, 2 min interval) during
      dialysis. The calf (no treatment) and biceps (normal saline) of the other side
      was used as control. RESULTS: Both models reliably induced muscle pain with
      similar intensities as assessed by visual analog scale. The DOMS exercise caused
      an increase of lactate in serum and the calf muscles of the DOMS leg. In
      addition, glutamate, PGE2 and substance P dialysate concentrations increased
      following contraction-induced pain stimulation (peak concentrations 125 +/- 20
      microM, 239 +/- 45 pg/ml and 60 +/- 11 pg/ml for glutamate, PGE2 and SP,
      respectively). This increase did not occur in the control leg (peak
      concentrations 97 +/- 12 microM, 114 +/- 26 pg/ml and 46 +/- 9 pg/ml for
      glutamate, PGE2 and SP, respectively). Concentrations of nitric oxide were lower
      in the DOMS than control leg, particularly during the first 4h of microdialysis.
      Injection of hypertonic saline into the biceps muscle caused a significant
      increase of dialysate glutamate concentrations (peak 50 +/- 3 microM) whereas
      glutamate remained constant after injection of normal saline (mean 26 +/- 1
      microM). Injection of hypertonic saline had no effect on lactate, PGE2 or NO
      levels. CONCLUSION: Our data support the notion that an inflammatory reaction may
      be involved in muscle soreness following eccentric exercise, whereas the
      injection of hypertonic saline into the muscle probably directly stimulates
      muscle nociceptors and causes glutamate release.

PMID- 12234057
TI  - Differential regulation of the expression of transporters associated with antigen
      processing, TAP1 and TAP2, by cytokines and lipopolysaccharide in primary human
      macrophages.
AB  - OBJECTIVE: Using microarray technique we analysed global changes in gene
      expression of interferon-y treated primary macrophages. Among the differential
      expressed genes identified we focussed on the expression of the transporters
      associated with antigen processing, TAP1 and TAP2, which are involved in the
      antigen presentation via MHC class 1. Patients suffering from TAP deficiency
      syndrome have clinical manifestations including recurrent bacterial infections of
      the respiratory tract and chronic necrotizing granulomatous skin lesions. This is
      one reason why the regulation of TAP gene expression in antigen presenting cells
      such as macrophages might provide important general insights into the generation
      of cellular immune response to multiple pathogens. Additionally IFN-alpha is
      important in adjuvant tumortherapie although the working mechanisms are unknown.
      Because of the possibility of the TAPs to be involved in these mechanisms we
      studied the expression of these transporters in human macrophages after
      stimulation with pro-inflammatory mediators. MATERIAL AND TREATMENT: Monocyte
      derived macrophages were treated for 24 h with either interferon-gamma,
      interferon-alpha, interleukin-1 (each 100 U/ml) or lipopolysaccharide (1
      microg/ml). METHODS: IFN-gamma induced gene expression was analysed using
      microarray technique. TAP expression was investigated by RT-PCR, northern blot-
      and western blot analysis. RESULTS: TAP1 and TAP2 were constitutively expressed
      at a low level. IFN-gamma upregulated the expression of both transporters. LPS
      caused an increase similar to the effect of IFN-gamma. Treatment with IFN-a
      stimulated also the expression, however, less than IFN-y. In contrast, IL-1beta
      stimulation had no effect. CONCLUSION: Our data show that the transporters
      associated with antigen presentation are differentially regulated by pro
      inflammatory mediators in human macrophages. The finding that IFN-alpha
      stimulates the expression of proteins involved in cytotoxic effector functions of
      macrophages contributes to the understanding of the immunoregulatory role of type
      1 interferons and may help to explain the efficacy of IFN-alpha in the treatment
      of tumors.

PMID- 12234058
TI  - Enhanced macrophage responsiveness to lipopolysaccharide and CD40 stimulation in
      a murine model of inflammatory bowel disease: IL-10-deficient mice.
AB  - OBJECTIVE: To elucidate the role of macrophages in the pathogenesis of
      inflammatory bowel disease, proinflammatory characteristics of macrophages were
      estimated in a murine model of spontaneous intestinal inflammation. MATERIALS AND
      METHODS: Peritoneal macrophages from IL-10deficient mice were stimulated with
      lipopolysaccharide (LPS) or an anti-CD40 monoclonal antibody (mAb). Cytokine
      release was assessed by enzyme-linked immunosorbent assay. CD40 expression was
      examined by two-color flow cytometric analysis. Induction of suppressor of
      cytokine signaling 3 (SOCS3) mRNA was evaluated by real-time quantitative RT-PCR.
      RESULTS: In the presence of LPS or anti-CD40 mAb, TNF-alpha and IL-12p70 release
      from macrophages of mutant mice was significantly higher than that from
      macrophages of wild-type mice. This may be due to the difference in IL-10
      production by macrophages, since activated macrophages of wild-type mice produced
      IL-10 in amounts sufficient to suppress an increased release of cytokines from
      activated macrophages of mutant mice. LPS and CD40 stimulation induced
      significantly high level of SOCS3 expression in macrophages of mutant mice in
      comparison to those of wild-type mice. CONCLUSIONS: Macrophages from a murine
      model of inflammatory bowel disease demonstrated enhanced responsiveness to
      immunological and bacterial stimuli. This suggests significant roles of
      macrophages in the pathogenesis of inflammatory bowel disease.

PMID- 12234059
TI  - Polyploidization and centrosome hyperamplification in inflammatory bronchi.
AB  - OBJECTIVE AND DESIGN: Inflammatory and tumorous bronchi were screened in order to
      obtain new tumor relevant cytogenetic parameters. MATERIAL OR SUBJECTS: Bronchial
      cells of 32 patients were cultivated by standard cell culture procedures.
      METHODS: Tetraploidy and aneuploidy was determined by enumeration of chromosome 7
      and 8 versus the number of centrosomes. The resulting data were correlated with
      histopathological data. RESULTS: Tetra- and aneuploidy of epithelial cells were
      detectable in 76% of tumor cell cultures, 75% of high grade inflammatory tissues
      and 40% of non- and low grade-inflammatory tissues. Additionally, we observed
      centrosome hyper-amplification and multipolar mitoses not only in the tumor but
      also in the early stages of inflammation. CONCLUSION: Inflammatory bronchi
      already show tumor-specific features and may consequently represent the
      preliminary genetic stage of cancer development in bronchi.

PMID- 12234060
TI  - Expression of 5-lipoxygenase mRNA is unchanged in the colon of patients with
      active inflammatory bowel disease.
AB  - BACKGROUND: In inflammatory bowel disease (IBD) the disease activity correlates
      with colonic concentrations of leukotrienes (LTs). The enzyme 5-lipoxygenase (5
      LO) is responsible for the enzymatic production of LTs. It has previously been
      demonstrated in experimental models of inflammation, that 5-LO is activated
      through intracellular translocation of the pre-formed enzyme, and increased
      constitutive activation of 5-LO has been demonstrated in idiopathic pulmonary
      fibrosis. The objective of the present study was to investigate whether de novo
      synthesis of 5-LO is increased in patients with quiescent IBD, or is induced
      during acute exacerbations of IBD. METHODS: Sixty-one individuals were included
      in the study. Twenty-eight had ulcerative colitis (UC), 21 had Crohn's disease
      (CD), and 12 were healthy controls. A standard rigid rectoscopy was performed in
      all individuals. The degree of inflammation was assessed using a semi
      quantitative scale. A mucosal biopsy was taken from the most inflamed area as
      judged macroscopically. mRNA for 5-LO was detected using a RT-PCR technique, and
      the assay applied was evaluated by control experiments. RESULTS: The expression
      of mRNA for 5-LO in colonic biopsies was similar in IBD patients with quiescent
      disease and healthy controls. When grouped according to endoscopically assessed
      disease activity the fraction of patients demonstrating 5-LO mRNA in colonic
      biopsies showed no significant change (p > 0,6; chi2 -test for trend).
      CONCLUSIONS: This study demonstrates no significant relationship between
      endoscopically assessed disease activity and relative presence of mRNA for 5-LO
      in colonic biopsies. Thus, there is no evidence of increased expression of 5-LO
      mRNA in either quiescent or active stages of IBD.

PMID- 12234061
TI  - Differential effects of nonsteroidal antiinflammatory drugs on the IL-1 altered
      expression of plasminogen activators and plasminogen activator inhibitor-1 by
      articular chondrocytes.
AB  - OBJECTIVE: To determine the in vitro effects of several nonsteroidal
      antiinflammatory drugs on the IL-1 altered expression and activity of tPA, uPA
      and PAI-1 by articular chondrocytes. METHODS: Bovine chondrocytes were cultured
      in alginate gel beads. Cells were treated with IL-1alpha in the presence or
      absence of drugs at various concentrations. Expression of mRNA for the
      plasminogen activators (uPA and tPA) and their inhibitor (PAI-1) were analyzed by
      RT-PCR-ELISA. The protein content of PAI-1 in culture media was deter mined by
      ELISA. PA activity was measured by a functional assay. RESULTS: All tested NSAIDs
      dose dependently inhibited the IL-1 induced mRNA expression of tPA, whereas only
      indomethacin and tiaprofenic acid were also able to reduce the expression of uPA.
      Expression of PAI-1 was elevated by IL-1 without an accompanying increase in
      secreted amounts of the inhibitor. Indomethacin, naproxen and tiaprofenic acid
      stimulated the release of PAI-1 into culture media, whereas meloxicam also
      induced expression of PAI-1 above IL-1 stimulated levels. CONCLUSION: In
      conclusion, our studies indicate that NSAIDs preferentially inhibit tPA
      expression by bovine articular chondrocytes. By increasing the production of PAI
      1 at therapeutical concentrations meloxicam could reduce PA activity, whereas the
      other NSAIDs tested mainly enhanced the release of this inhibitor from the
      extracellular matrix. In how far this would affect the enzyme-inhibitor balance
      within cartilage has to be determined in further studies.

PMID- 12234062
TI  - Expression of HER-2/neu receptor protein in adrenal tumors.
AB  - The HER-2/neu protein is overexpressed in many human carcinomas obtained from
      different tissues and may represent a useful target for therapy with the
      commercially available monoclonal antibody trastuzumab (herceptin). Novel
      therapeutic options are needed for metastasized adrenocortical cancer. Therefore,
      we studied expression of the HER-2/neu cell surface receptor protein using three
      different antibodies in 12 adrenal adenomas, 17 adrenocortical carcinomas and 5
      pheochromocytomas. Normal adrenals (n = 5) served as controls. One adenoma showed
      very weak membranous immunostaining with the Dako antibody, two others showed a
      nonspecific cytoplasmic staining pattern. A nonspecific reaction in the cytoplasm
      was demonstrable in seven carcinomas with the Novocastra antibody. In all
      pheochromocytomas, a granular intracytoplasmic and, rarely, slightly membranous
      immunostaining with the Dako antibody was found. From our data we conclude that
      specific and significant membranous immunostaining indicating strong
      overexpression (grade 3) of HER-2/neu protein is not present in adrenocortical
      tumors. The granular cytoplasmic immunostaining of the medulla may be helpful for
      differentiation of adrenocortical tumors from pheochromocytomas.

PMID- 12234064
TI  - The prognostic significance of the semiquantitatively determined estrogen
      receptor content of breast carcinomas. A clinicopathological study.
AB  - Response of breast carcinomas to tamoxifen treatment depends, among others, on
      the estrogen receptor status. The estrogen receptor content was
      semiquantitatively determined in immunostained sections of stage 1 and 2 cancers
      of patients who had undergone tumor excision, tamoxifen treatment, adjuvant
      chemotherapy and radiotherapy. Weighted scores of the estrogen receptor content
      of the tumors were established by calculating the arithmetic means of the
      intensity of stained nuclei and the number of positively stained nuclei.
      Statistically, a cut-off value of > or = 2.1 signified a good prognosis; all
      patients whose tumors disclosed a weighted score of > or = 2.1 were alive and
      free of disease at the 10-year postoperative follow-up examination. On the other
      hand, one third of the patients whose carcinomas had a weighted score of < 2.1
      presented with locally recurrent cancer, distant metastases, or both during the
      follow-up observation period. The statistically significant association between
      the patients' 10-year event-free survival and carcinomas with a weighted score of
      > or = 2.1 may serve oncologists in their decision making with respect to
      hormonal treatment.

PMID- 12234063
TI  - P63 expression in papillary and anaplastic carcinomas of the thyroid gland: lack
      of an oncogenetic role in tumorigenesis and progression.
AB  - P53 is considered one of the most important tumor suppressor genes and is mutated
      in up to 50% of all neoplasms. Well-differentiated thyroid carcinomas (WDTCs)
      only infrequently harbor p53 mutations. In contrast, these genetic alterations
      have been described in approximately 85% of anaplastic thyroid carcinomas and are
      considered a fundamental event in the malignant progression of WDTCs. However,
      alternative mechanisms to overcome p53 tumor suppressing properties in WDTCs and
      anaplastic carcinomas (ACs) have not been clarified to date. p63, a p53
      homologue, has been recently characterized. In contrast to p53, p63 gene encodes
      six isoforms, three with transactivating and three with dominant negative (deltaN
      p63) activities on p53 reporter genes. We hypothesized that overexpression of
      deltaN-p63 isoforms might constitute an alternative mechanism to overcome p53
      tumor suppressing properties in WDTCs and ACs lacking p53 alterations. We
      semiquantitatively evaluated p53 and p63 immunoexpression in 12 papillary
      carcinomas (PC) and 11 anaplastic carcinomas. Only nuclear expression was
      considered specific. All PCs lacked p53 expression; at variance, nine ACs showed
      p53 immunoreactivity (+: 1 case; ++: 6 cases; +++: 2 cases). In PCs, p63
      expression was restricted to scattered neoplastic cells juxtaposed to the
      basement membrane of papillary projections and to foci of squamous metaplasia. In
      ACs, p63 expression was observed in three cases, one of which lacked concurrent
      p53 immunoexpression. Our results do not support the hypothesis that p63 might
      constitute an alternative mechanism to overcome p53 tumor suppressing properties
      in thyroid neoplasms.

PMID- 12234065
TI  - Apoptosis in thymic epithelial tumors.
AB  - We studied Fas/FasL, Bcl-2, and M30 CytoDeath in five cases of normal thymus and
      41 cases of thymic epithelial tumors (TETs). In normal thymus, Fas was expressed
      in all epithelial cells, but not in thymic lymphocytes; FasL was weakly expressed
      only in medullary epithelium and Hassal's corpuscles. In TETs, Fas was expressed
      in all epithelial cells and lymphocytes, while FasL was differently expressed in
      epithelial cells of different subtypes of TETs, i.e., type A (2/2), AB (12/12),
      B1 (0/9), B1/B2 (0/3), B2 (0/1), B2/B3 (1/3), B3 (6/10) and C (1/1), but not in
      lymphocytes. Bcl2 protein was strongly expressed in medullary-derived lymphocytes
      of normal thymus and TETs, and weakly expressed only in medullary (spindle)
      epithelium of TETs. On M30 CytoDeath immunostaining, apoptotic indices were very
      low in all TETs (0-1.2). In conclusion, since FasL was expressed on the
      epithelial cells of lymphocyte-depleted (LD) areas of type B2/B3 and/or LD
      subtypes (type A, AB, B3, C), FasL expression could be relevant for the
      intracytoplasmic processes of T-cell selection and the regulation of the lymphoid
      cells inside the tumor, at least partly. However, tumorigenesis of TETs is not
      necessarily induced by abrogation of apoptosis.

PMID- 12234066
TI  - Effects of irradiation on biological behavior of carcinoma cells under carcinoma
      stromal cell interaction and air-liquid interface: a possible model for testing
      radiosensitivity of carcinoma of the upper aerodigestive tract using a collagen
      gel culture system.
AB  - Carcinoma-stromal cell interaction and air-liquid interface (ALI) constitute a
      specific microenvironment that modulates the biological behavior of carcinoma
      cells of the upper aerodigestive tract. Although radiotherapy is a useful tool
      for treating carcinomas of this organ, effects of irradiation on carcinoma cells
      under carcinoma-stromal cell interaction and ALI are unclear. To address this
      issue, we examined the effects of irradiation on the proliferation and apoptosis
      of squamous cell carcinoma cell lines (KB and HEp-2), using three-dimensional
      collagen gel culture with both carcinoma-stromal cell interaction and ALI. During
      the second week after irradiation with or without the two factors mentioned
      above, bromodeoxyuridin (BrdU) uptake and apoptosis of KB, and HEp-2 cell types
      decreased and increased, respectively. After this stage, the carcinoma cells with
      these two factors actively re-proliferated together with increased BrdU uptake
      and decreased apoptosis, whereas the magnitude of these parameters was
      considerably lower in culture without these factors. We applied our method to
      carcinoma tissues obtained from several clinical cases. At the same stage, the
      irradiated carcinoma cells replicated the phenomena observed in cell lines. The
      data indicate that carcinoma-stromal cell interaction and ALI together promote
      the re-proliferation of irradiated carcinoma cells and their decreased apoptosis,
      suggesting that our method is a possible model for testing radiosensitivity of
      carcinomas in a more physiological condition.

PMID- 12234067
TI  - Focal sarcoid-like change of the thyroid gland. A possible consequence of
      aspiration cytology?
AB  - An unusual case of focal accumulation of sarcoid-like granulomas occurring within
      the thyroid gland of a 43-year-old female patient is reported. The granulomas
      were found solely at the site of previous fine needle aspiration biopsy. The
      follow-up did not show any symptoms of systemic granulomatous disease. The
      pathogenesis of this lesion is discussed.

PMID- 12234068
TI  - Macrocystic serous adenoma of the pancreas.
AB  - Macrocystic serous adenoma of the pancreas (MSAP) is a rare neoplasm. Its
      preoperative diagnosis by physical examination and imaging studies is
      challenging, if not impossible. In recent years, a few cases of MSAP with correct
      cytodiagnosis by transabdominal fine-needle aspiration (TFNA) have been
      documented. This paper reports two cases of MSAP that were successfully diagnosed
      by TFNA cytology. Two adult women presented with epigastric discomfort. Abdominal
      imaging studies revealed a large pancreatic cystic lesion in both cases. TFNAs of
      the pancreatic lesions were subsequently performed and revealed a clear serous
      fluid containing small monolayered sheets of benign cuboidal epithelial cells
      with scant, clear or granular cytoplasm, vesicular nuclei and micronucleoli. The
      cell cytoplasm stained positively with periodic acid-Schiff (PAS) and negatively
      with PAS with prior digestion with diastase (PASD). The cytological findings in
      both cases were similar and suggested a serous cystadenoma. The two pancreatic
      lesions were removed by Whipple's operation. They showed features of a
      macrocystic serous adenoma of the pancreas that were characterized by a small
      number of large cystic cavities lined by a single layer of non-mucus secreting,
      PAS-positive and PASD-negative cuboidal epithelial cells. By electron microscopy,
      the epithelial lining cells showed short and aborted apical microvilli, well
      formed desmosomes and a large amount of intracytoplasmic glycogen, suggesting a
      centroacinar ductal cell origin.

PMID- 12234069
TI  - A case of segmental mediolytic arteriopathy involving both intracranial and
      intraabdominal arteries.
AB  - Segmental mediolytic arteriopathy (SMA) is an uncommon nonatherosclerotic and
      nonvasculitic arteriopathy. This disease is characterized by lytic degeneration
      of the arterial media, intramural dissection and thrombosed or ruptured aneurysm.
      SMA mainly involves the intraabdominal arterial system, resulting in
      intraabdominal and retroperitoneal hemorrhage. However, only a few cases of SMA
      with involvement of intracranial arteries have been reported. Here, we present a
      case of SMA developing subarachnoid hemorrhage due to dissection of the internal
      carotid and vertebral arteries. This patient was a 48-year-old male who died 13
      days after admission for sudden loss of consciousness. Computed tomography showed
      subarachnoid hemorrhage. At autopsy, the affected vessels included the right
      vertebral, left internal carotid, superior mesenteric, bilateral renal and left
      external iliac arteries. Histopathologically, the arteries showed segmental lytic
      degeneration and disappearance of medial smooth muscle cells, medial dissection
      and formation of pseudo-aneurysms, the wall of which consisted of a thin membrane
      of the adventitia. These histopathological features mimicked an entire wall
      dissection type of intracranial dissecting aneurysm, which exclusively affects
      the vertebro-basilar system. Thus, SMA should be considered a possible underlying
      disease in patients with spontaneous dissection of intracranial arteries.

PMID- 12234070
TI  - Epithelioid hemangioendothelioma with osteoclast-like giant cells.
AB  - Epithelioid hemangioendothelioma is an unusual entity of intermediate malignant
      vascular tumors and rarely admixes with multinucleated osteoclast-like giant
      cells. We describe such a case in a 50-year-old woman with an 1-year follow-up
      period. When the patient was 39 years old, a 0.7 x 1-cm firm mass was found in
      the left neck. She developed ascites three years later. At that time, the
      specimen from the neck mass was excised and found to be composed of cords of
      epithelioid cells in a myxoid hyaline stroma. Scattered intracytoplasmic vacuoles
      were seen. Immunohistochemical studies confirmed the diagnosis of epithelioid
      hemangioendothelioma. Abdominal ultrasonography and computed tomographic scan
      revealed multiple low density areas in the liver. Eleven years later, a
      metastatic lesion was found in the thoracic spine at the level of Th7-8. The
      histologic findings were basically similar to those of the left neck mass.
      However, because of the presence of Kp-1-positive multinucleated osteoclast-like
      giant cells throughout the tumor, the thoracic lesion was diagnosed as an
      epithelioid hemangiothelioma with osteoclast-like giant cells. This unique form
      of epithelioid hemangioendothelioma is extremely rare and should be distinguished
      from other benign and malignant tumors with osteoclast-like giant cells.

PMID- 12234071
TI  - Mother-infant interactions in western Lowland Gorillas (Gorilla gorilla gorilla):
      spatial relationships, communication, and opportunities for social learning.
AB  - This study investigated mother-infant interactions in lowland gorillas (Gorilla
      gorilla gorilla) with particular focus on the relative role of mothers and
      infants in creating situations that are potentially conducive to infant social
      learning. Eleven gorilla mother-infant dyads were focally observed in weekly 1-hr
      sessions for 12 months. Spatial relationships were affected by age as well as by
      ambient temperature. Although the youngest infant was encouraged by its mother to
      walk and climb, mothers showed little or no encouragement in other contexts. In
      contrast, infants were quite interested in their mothers' activities, on some
      occasions repeated their mother's behavior, and actively encouraged their mothers
      to share food, play, or follow them. These findings suggest that gorilla infants
      are more active than their mothers in creating situations that are potentially
      conducive to the acquisition of knowledge or skills.

PMID- 12234072
TI  - Thermoregulatory behavior in infant Norway rats (Rattus norvegicus) and Syrian
      golden hamsters (Mesocricetus auratus): arousal, orientation, and locomotion.
AB  - The responses of 2- and 8-day-old rats (Rattus norvegicus) and hamsters
      (Mesocricetus auratus) to thermal stimulation were assessed in 4 experiments. In
      Experiment 1, the surface underlying the pup was cooled, and the latency to
      escape to a region of warmth was measured. Experiment 2 required pups to locomote
      farther to gain access to warmth. Experiment 3 was similar to Experiment 1 except
      the underlying surface was heated. Finally, in Experiment 4, locomotor behavior
      was assessed during isothermal cooling in which there was no possibility for
      escape. In general, hamsters exhibited more rapid and robust responses to thermal
      stimulation than rats. A framework for interpreting these results is presented
      emphasizing how differences in locomotor and thermogenic capabilities influence
      thermoregulatory behavior under different task conditions.

PMID- 12234073
TI  - Contributions of endothermy to huddling behavior in infant Norway rats (Rattus
      norvegicus) and Syrian golden hamsters (Mesocricetus auratus).
AB  - Infant Syrian golden hamsters (Mesocricetus auratus) do not exhibit endogenous
      heat production before 3 weeks of age and do not huddle effectively during cold
      exposure, gaining little thermoregulatory benefit from the presence of multiple
      littermates. In contrast, infant Norway rats (Rattus norvegicus) produce heat
      endogenously and are effective at maintaining elevated body temperatures by
      huddling. Therefore, the ineffective huddling of infant hamsters may be due to
      the absence of endogenous heat production. The huddling behavior of infants in
      mixed huddles of 8-day-old hamsters and weight-matched 4-5-day-old rats was
      observed to explore this possibility. The results indicate that hamsters, even
      when cold, effectively gain access to heat-producing rats, supporting the idea
      that endothermy contributes to the behavior of huddling by providing heat to each
      individual and thermal stimuli to other infants to support aggregation.

PMID- 12234074
TI  - Recognition of conspecific odors by laboratory rats (Rattus norvegicus) does not
      show context specificity.
AB  - This experiment investigated how contextual cues affect recognition of
      conspecific odors in laboratory rats (Rattus norvegicus). Rats received 5
      encounters with the same odor in the same context. For the 6th test encounter,
      all rats received a simultaneous presentation of the original odor and a novel
      odor. The authors tested 1 group of rats (context same) in the same context as
      before. For the remaining 2 groups, the test encounter was in a different context
      that 1 group (context different) had experienced but that 1 group (context novel)
      had not. A significant preference to investigate the novel odor by context-same
      and context-different rats, but not by context-novel rats, suggests that odor
      recognition can occur following transfer to a different, but familiar, test
      context, indicating a lack of context specificity.

PMID- 12234075
TI  - Detection thresholds for intensity increments in a single harmonic of synthetic
      Japanese macaque (Macaca fuscata) monkey coo calls.
AB  - There is evidence that Japanese macaques (Macaca fuscata) are extremely sensitive
      to dynamic changes in the relative amplitudes of coo call harmonics during
      discrimination tests. To verify this evidence using more controlled stimulus
      configurations, the authors examined threshold sensitivity of macaque monkeys to
      amplitude increments added to the standard level of coo call harmonics.
      Psychophysical threshold determination methods paralleled those used previously
      to determine macaque sensitivity to amplitude increments added to vowel-like
      stimuli. Variation was detectable although thresholds were elevated relative to
      those obtained with vowel-like stimuli in another investigation (C. G. Le Prell,
      A. J. Niemiec, & D. B. Moody, 2001). This elevation was probably a function of
      natural amplitude modulation in the standard stimuli.

PMID- 12234076
TI  - Grooming and yawning trace adjustment to unfamiliar environments in laboratory
      Sprague-Dawley rats (Rattus norvegicus).
AB  - The authors studied grooming and yawning caused by mild stress in laboratory
      Sprague-Dawley rats (Rattus norvegicus). Two groups received 3 and 6 sequences of
      5 foot shocks at random intervals (RI) and fixed intervals (FI), respectively. A
      3rd group was not shocked (NS). The groups were exposed for 60 min twice.
      Grooming did not differ among groups, but yawning diminished with RI. Yawning
      increased and grooming decreased with the 2nd exposure, except in RI in which
      grooming increased. In NS and FI, grooming prevailed during the first 20 and 30
      min, respectively, whereas yawning dominated the remainder of the time. In RI,
      grooming occurred more than yawning. An upward shift on this scale causes
      grooming to substitute yawning, whereas a downward shift causes the reverse
      effect.

PMID- 12234077
TI  - Prenatal experience and postnatal perceptual preferences: evidence for
      attentional-bias in bobwhite quail embryos (Colinus virginianus).
AB  - Previous studies have indicated that concurrent multimodal sensory stimulation
      can interfere with prenatal perceptual learning. This study further examined this
      issue by exposing 3 groups of bobwhite quail embryos (Colinus virginianus) to (a)
      no supplemental stimulation, (b) a bobwhite maternal call, or (c) a maternal call
      paired with a pulsating light in the period prior to hatching. Experiments
      differed in terms of the types of stimuli presented during postnatal preference
      tests. Embryos receiving no supplemental stimulation showed no preference between
      stimulus events in all testing conditions. Embryos receiving exposure to the
      unimodal maternal call preferred the familiar call over an unfamiliar call
      regardless of the presence or absence of pulsating light during testing. Embryos
      exposed to the call-light compound preferred the familiar call only when it was
      paired with the light during testing. These results suggest that concurrent
      multimodal stimulation does not interfere with prenatal perceptual learning by
      overwhelming the young organism's limited attentional capacities. Rather,
      multimodal stimulation biases what information is attended to during exposure and
      subsequent testing.

PMID- 12234078
TI  - Imitation of conditional discriminations in pigeons (Columba livia).
AB  - In the present experiments, the 2-action method was used to determine whether
      pigeons could learn to imitate a conditional discrimination. Demonstrator pigeons
      (Columba livia) stepped on a treadle in the presence of 1 light and pecked at the
      treadle in the presence of another light. Demonstration did not seem to affect
      acquisition of the conditional discrimination (Experiment 1) but did facilitate
      its reversal of the conditional discrimination (Experiments 2 and 3). The results
      suggest that pigeons are not only able to learn a specific behavior by observing
      another pigeon, but they can also learn under which circumstances to perform that
      behavior. The results have implications for proposed mechanisms of imitation in
      animals.

PMID- 12234079
TI  - Maternal responsiveness to infant Norway rat (Rattus norvegicus) ultrasonic
      vocalizations during the maternal behavior cycle and after steroid and
      experiential induction regimens.
AB  - When removed from the nest and placed in a cool environment, Norway rat (Rattus
      norvegicus) pups emit ultrasonic vocalizations that can elicit maternal search
      behavior. The authors examined the behavior of pregnant dams, mothers, and virgin
      females during exposure to a pup that was either warm and silent or cool and
      vocalizing. Results indicate potentiated maternal reactions to a vocalizing pup:
      Mothers approached and maintained proximal orientation to a vocalizing pup far
      more than did virgin females. Elevated levels of proximal orientation appeared
      within hours of birth, increased during the 1st week postpartum, and declined by
      the time of weaning. Estrogen plus progesterone administration facilitated virgin
      females' proximal orientation toward vocalizing pups, whereas prolonged exposure
      to pups in the absence of hormones was without effect, suggesting that the
      ontogeny of the maternal response is regulated, at least in part, by maternal
      hormones.

PMID- 12234080
TI  - Stimulus control of maternal responsiveness to Norway rat (Rattus norvegicus) pup
      ultrasonic vocalizations.
AB  - Mother rats (Rattus norvegicus; 6 to 8 days postpartum) approach and maintain
      proximal orientation to a pup that is emitting ultrasonic vocalizations (USVs)
      far more than do virgin females (W. J. Farrell & J. R. Alberts, 2002). We used a
      playback regimen to examine the roles of acoustic and nonacoustic cues in
      regulating maternal proximal orientation toward vocalizing pups. When presented
      with recorded USVs, mothers of 6- to 8-day-old pups and nulliparous virgin
      females exhibited equivalent levels of proximal orientation toward the playback
      speaker. Mothers did show enhanced proximal orientation toward recorded USVs,
      however, if a silent pup was positioned below the speaker. Pup odors appear to be
      crucial for the maternal response to vocalizing pups, as peripherally induced
      anosmia attenuated maternal proximal orientation toward a vocalizing pup.
      Furthermore, spatial contiguity between olfactory and auditory stimuli was
      required for a maximal maternal response.

PMID- 12234081
TI  - Mice (Mus musculus) learn a win-shift but not a win-stay contingency under water
      escape motivation.
AB  - Twenty mice (Mus musculus), the second filial generation offspring from a C57BL/6
      and DBA/2J cross, received spatial win-shift and win-stay water escape training
      within a mixed design in which all mice received both types of training.
      Acquisition under win-shift was superior to win-stay with respect to errorless
      trials and latencies regardless of the order in which the procedures were
      experienced. Win-stay responding did not exceed chance levels during any training
      phase. These data contradict the claim that win-stay training is the more easily
      acquired of the 2 acquisition strategies under aversive motivation.

PMID- 12234082
TI  - Methods for obtaining menstrual-cycle data in menstrual-synchrony studies:
      commentary on Schank (2001).
AB  - J. C. Schank (2001) claimed to identify 2 categories of error-measurement error
      and recall biases-in the methodology used in studies of menstrual synchrony. This
      commentary focuses on the 2nd of these, recall biases, and other errors that he
      argued may result from "allowing participants to fill out menstrual-cycle-onset
      calendars" (p. 3). J. C. Schank's detailed discussion of various types of recall
      biases is inappropriate and misleading given that the majority of menstrual
      synchrony studies have used prospective menstrual calendars. The use of menstrual
      calendars is a well-accepted method in a number of research areas and demands
      little of participants. J. C. Schank questioned the validity of menstrual
      calendar data on the basis of assumptions about recall bias for which he had no
      evidence.

PMID- 12234083
TI  - Menstrual synchrony can be assessed, inherent cycle variability notwithstanding:
      commentary on Schank (2001).
AB  - J. C. Schank (2001) argued that biases in the calculation of synchrony (due to
      inherent variability in the menstrual cycle) and in respondents' recall of
      menstrual dates can produce spurious results. In this commentary, the major flaws
      in J. C. Schank's arguments regarding the calculation of synchrony are presented.
      Low standard deviations (< 2.0) of interwomen cycle lengths were found in a
      reanalysis of the Bedouin family data (A. Weller & L. Weller, 1997). This
      obviates J. C. Schank's major assumption that a high degree of cycle variability
      exists and his concern that high variability produces a spurious increase of
      onset differences over time. Furthermore, research that has used random control
      groups has found significantly greater levels of synchrony in their experimental
      groups, refuting J. C. Schank's arguments.

PMID- 12234084
TI  - A multitude of errors in menstrual-synchrony research: replies to Weller and
      Weller (2002) and Graham (2002).
AB  - This article replies to commentaries by A. Weller and L. Weller (2002) and by C.
      A. Graham (2002). The author of this reply argues that A. Weller and L. Weller
      merely defined away the problem of cycle variability for synchrony by assuming
      either that all cycles are 28-days long or that the expected difference between 2
      cycles is 1/4 the mean of the cycles of 2 rhythms. In her commentary, C. A.
      Graham stated that A. Weller and L. Weller's later research did not use recall
      data, but the author of this reply shows that this is not true. Menstrual
      synchrony research taken as a whole is plagued by a multitude of systematic
      errors that lead inevitably to the conclusion that there is no evidence for
      menstrual synchrony among women.

PMID- 12234085
TI  - Pharmacologic options for the management of multiple sclerosis symptoms.
AB  - Multiple sclerosis (MS) is a disease with a wide-ranging impact on physical
      functioning. Although pharmacotherapy plays an indispensable role in the
      management of MS symptoms, optimal disease management requires a
      multidisciplinary approach that combines medication, rehabilitation, and patient
      education. Successful control of symptoms is critical to quality of life for MS
      patients. Immunomodulating drugs provide a means of controlling the underlying
      disease process, but they are not a cure. This places responsibility on health
      care providers to control a patient's MS-related symptoms to limit disability and
      delay impairment in the activities of daily living. Owing to the importance of
      symptom control, comprehensive patient evaluations should be performed at regular
      intervals to determine the extent of neurological damage and disease progression
      and to address changing patient needs. The goal of interventions should be not
      only to treat the primary and secondary symptoms of MS but also to provide access
      to the psychosocial support that will help MS patients and their families
      continue to cope as disease status changes.

PMID- 12234086
TI  - The fugl-meyer assessment of motor recovery after stroke: a critical review of
      its measurement properties.
AB  - Measurement of recovery after stroke is becoming increasingly important with the
      advent of new treatment options under investigation in stroke rehabilitation
      research. The Fugl-Meyer scale was developed as the first quantitative evaluative
      instrument for measuring sensorimotor stroke recovery, based on Twitchell and
      Brunnstrom's concept of sequential stages of motor return in the hemiplegic
      stroke patient. The Fugl-Meyer is a well-designed, feasible and efficient
      clinical examination method that has been tested widely in the stroke population.
      Its primary value is the 100-point motor domain, which has received the most
      extensive evaluation. Excellent interrater and intrarater reliability and
      construct validity have been demonstrated, and preliminary evidence suggests that
      the Fugl-Meyer assessment is responsive to change. Limitations of the motor
      domain include a ceiling effect, omission of some potentially relevant items, and
      weighting of the arm more than the leg. Further study should test performance of
      this scale in specific subgroups of stroke patients and better define its
      criterion validity, sensitivity to change, and minimal clinically important
      difference. Based on the available evidence, the Fugl-Meyer motor scale is
      recommended highly as a clinical and research tool for evaluating changes in
      motor impairment following stroke.

PMID- 12234087
TI  - Muscle weakness and cocontraction in upper limb hemiparesis: relationship to
      motor impairment and physical disability.
AB  - The purpose of this article is to describe the relationship between poststroke
      upper limb muscle weakness and cocontraction, and clinical measures of upper limb
      motor impairment and physical disability. Electrormyographic (EMG) activity of
      the paretic and nonparetic wrist flexors and extensors of 26 chronic stroke
      survivors were recorded during isometric wrist flexion and extension. The root
      mean square (RMS) of the EMG signal was used as a measure of strength of
      contraction. A ratio of RMS of antagonist and agonist muscles was used as a
      measure of cocontraction. Upper limb motor impairment and physical disability
      were assessed with the Fugl-Meyer motor assessment (FMA) and the arm motor
      ability test (AMAT), respectively. The strength of muscle contraction was
      significantly stronger in the nonparetic limb (P < 0.001). The degree of
      cocontraction was significantly greater in the paretic limb (P < 0.001). The
      strength of muscle contraction in the paretic limb correlated significantly with
      FMA (r = 0.62 to 0.87, P < or = 0.001) and AMAT (r = 0.66 to 0.80, P < or =
      0.001) scores. Similarly, the degree of cocontraction correlated significantly
      with FMA (r = -0. 70 to -0.64, P < or = 0.001) and AMAT (r = -0. 72 to -0.62, P <
      or = 0.001) scores. Muscle weakness and degree of cocontraction correlate
      significantly with motor impairment and physical disability in upper limb
      hemiplegia. This relationship may provide insights toward development of specific
      interventions. However, additional studies are needed to demonstrate a cause and
      effect relationship.

PMID- 12234088
TI  - Narrative and procedural discourse production by severely aphasic patients.
AB  - Five cbronically aphasic subjects were trained on a computerized iconographic
      communication system (C-VIC). Their performance in producing single sentences
      scripts. and narratives was assessed using both spoken English and C-VIC. The
      requisite vocabulary necessary and the narrative complexity of the target
      productions were controlled. Subject performance using C-VIC indicates that the
      ability to construct discourse at the macrostructural level is largely intact.
      Despite significant improvements in spoken production after C-VIC training,
      especially at the single sentence level, the subjects' spoken discourse remains
      severely impaired by their failures at the microlinguistic level. These results
      point to the limits of currently available approaches to the remediation of
      aphasia and suggest avenues for future research.

PMID- 12234089
TI  - Hand motor recovery after stroke: a transcranial magnetic stimulation mapping
      study of motor output areas and their relation to functional status.
AB  - The respective contributions of the stroke and undamaged hemispheres to motor
      recovery after stroke remains controversial. The aim of this article is to
      evaluate the relationship between location and size of cortical motor areas and
      outcome after stroke. Twelve controls and 12 stroke patients were studied. Hand
      cortical motor output areas were determined using transcranial magnetic
      stimulation. Motor-evoked potentials were recorded simultaneouslyfrom both hands.
      Functional motor abilities were evaluated using well-validated measures. Surface
      area, weighted surface area, and center of gravity of motor output areas were
      calculated. Different patterns of motor output areas to the paretic band were
      observed; there was no motor output from the stroke hemisphere in patients with
      poor outcome, contrasting to large motor output area in the stroke hemisphere in
      patients with good outcome, regardless of infarct size or location. A significant
      correlation was found between measures of motor outcome in the stroke-affected
      upper extremity and both the surface area and weight of the central motor output
      area in the stroke hemisphere. No ipsilateral motor response was obtained after
      stimulation of either hemisphere. These data support an association between
      preservation of cortical motor output area to the paretic hand in the stroke
      hemisphere and good motor outcome.

PMID- 12234090
TI  - Assessing the motor status score: a scale for the evaluation of upper limb motor
      outcomes in patients after stroke.
AB  - The Motor Status Scale (MSS) measures shoulder, elbow (maximum score = 40),
      wrist, hand, and finger movements (maximum score = 42), and expands the
      measurement of upper extremity impairment and disability provided by the Fugl
      Meyer (FM) score. This work examines the interrater reliability and criterion
      validity of the MSS performed in patients admitted to a rehabilitation hospital
      21 +/- 4 days after stroke. Using the MSS and the FM, 7 occupational therapists
      masked to each other's judgments, evaluated 12 consecutive patients with stroke.
      Two therapists evaluated 6 additional patients on consecutive days. Intraclass
      correlation coefficients were significant for each group of raters for the
      shoulder/elbow and for the wrist/band (P < 0.0001); test-retest measures were
      also significant for the shoulder/elbow (Pearson correlation coefficient r =
      0.99, P < 0.004) and for the wrist/hand (Pearson correlation coefficient r =
      0.99, P < 0.003). The internal item consistency for the overall MSS was
      significant (Cronbach alpha = 0.98, P < 0.0001). Finally the correlation between
      the MSS and the FM (R2 = 0.964) was significant (P < 0.0001). The MSS affords a
      reliable and valid assessment of upper limb impairment and disability following
      stroke.

PMID- 12234091
TI  - Modified constraint-induced therapy after subacute stroke: a preliminary study.
AB  - OBJECTIVE: To determine the efficacy of a modified constraint-induced therapy
      (mCIT) administered to patients with subacute stroke. DESIGN: Prospective,
      multiple-baseline, before-after, randomized clinical trial. SETTING: Subacute
      outpatient clinic. SUBJECTS: Fourteen patients with subacute stroke who exhibited
      learned nonuse and stable motor deficits in their affected upper limbs.
      INTERVENTION: Four patients participated in half-hour, structured physical and
      occupational therapy sessions that emphasized affected arm use in valued
      functional activities, 3 times per week for 10 weeks. Their less affected upper
      limbs were restrained 5 days per week during 5 hours identified as times of
      frequent use (mCIT). Five patients received regular therapy (TR) with similar
      therapeutic contact time to mCIT and 5 patients received no therapy (CON). MAIN
      OUTCOME MEASURES: The Fugl-Meyer Assessment of Motor Recovery (Fugl), Action
      Research Arm (ARA) test, and Motor Activity Log (MAL). RESULTS: After
      intervention, Fugl, ARA, and MAL scores remained virtually the same for TR and
      CON groups; scores improved by 11.4 and 11.5points, respectively, on the Fugl and
      ARA for the mCIT group. Amount and quality of arm use, as measured by the MAL,
      also improvedfor mCIT patients (2.49 and 0.47, respectively). CONCLUSIONS: mCIT
      may be an efficacious method of improving affected arm function and use in stroke
      patients exhibiting learned nonuse.

PMID- 12234092
TI  - Interactions of the 18.5-kDa isoform of myelin basic protein with Ca(2+)
      calmodulin: in vitro studies using fluorescence microscopy and spectroscopy.
AB  - The interactions of the 18.5-kDa isoform of myelin basic protein (MBP) with
      calmodulin (CaM) in vitro have been investigated using fluorescence microscopy
      and spectroscopy. Two forms of MBP were used: the natural bovine C1 charge isomer
      (bMBP/C1) and a hexahistidine-tagged recombinant murine product (rmMBP), with
      only minor differences in behaviour being observed. Fragments of each protein
      generated by digestion with cathepsin D (EC 3.4.23.5) were also evaluated. Using
      fluorescence microscopy, it was shown that MBP and CaM interacted in the presence
      of Ca2+ under a variety of conditions, including high urea and salt
      concentrations, indicating that the interaction was specific and not merely
      electrostatic in nature. Using cathepsin D digestion fragments of MBP, it was
      further shown that the carboxyl-terminal domain of MBP interacted with Ca(2+)
      CaM, consistent with our theoretical prediction. Spectroscopy of the intrinsic
      fluorescence of the sole Trp residue of MBP showed that binding was cooperative
      in nature. The dissociation constants for formation of a 1:1 MBP-Ca(2+)-CaM
      complex were determined to be 2.1 +/- 0.1 and 2.0 +/- 0.2 microM for bMBP/C1 and
      rmMBP, respectively. Fluorescence spectroscopy using cathepsin D digestion
      fragments indicated also that the carboxyl-terminal region of each protein
      interacted with Ca(2+)-CaM, with dissociation constants of 1.8 +/- 0.2 and 2.8 +/
      0.9 microM for the bMBP/C1 and rmMBP fragments, respectively. These values show
      a roughly 1000-fold lower affinity of MBP for CaM than other CaM-binding
      peptides, such as myristoylated alanine-rich C-kinase substrate, that are
      involved in signal transduction.

PMID- 12234093
TI  - A role for cell cycle proteins in the serum-starvation resistance of Epstein-Barr
      virus immortalized B lymphocytes.
AB  - Epstein-Barr virus (EBV) is a B-lymphotropic human herpes virus that infects B
      lymphocytes and is associated with a broad spectrum of benign and malignant
      diseases. B cell infection by EBV causes indefinite cell proliferation that
      results in the development of immortalized lymphoblastoid cell lines (LCLs). We
      found that SNU-1103, a latency type III EBV-transformed LCL developed from a
      Korean cancer patient, resisted the G1 arrest that was normally caused by serum
      starvation. Western blot analyses revealed several alterations in the expression
      of key regulatory cell cycle proteins involved in the G1 phase. High expression
      of cyclin D2 and time-dependent increases in cyclin-dependent kinase 6 (CDK6) and
      cyclin D3 were observed in SNU-1103 during serum starvation. Very unexpectedly,
      in SNU-1103, the key G1 phase CDK inhibitor p21CiP1 was expressed at a
      consistently high level, while p27KiP1 expression was increased. Of three pRb
      family proteins, pRb expression was reduced and it became hypophosphorylated in
      SNU-1103 during serum starvation. Instead, p107 and p130 were expressed at
      consistently high levels in SNU-1103 during serum starvation. In conclusion,
      compared with an EBV-negative BJAB cell line, multiple cell cycle regulatory
      proteins were abnormally or inversely expressed in SNU-1103 during serum
      starvation.

PMID- 12234094
TI  - Screening regulatory sequences from bacterial artificial chromosome DNA of alpha-
      and beta-globin gene clusters.
AB  - In the forthcoming postgenomic era, identification of regulatory DNA sequences is
      becoming increasingly important for characterizing DNA-binding proteins and for
      elucidating the regulatory mechanisms of gene expression. Presently, there lack
      efficient methods to broadly screen and identify DNA regulatory elements on a
      large scale. We established herein an efficient strategy to screen regulatory
      sequences from bacterial artificial chromosome (BAC) DNAs containing human alpha-
      and beta-globin gene clusters based on polymerase chain reaction and
      electrophoretic mobility shift assay (EMSA) techniques without purified
      transcription factors. Twenty-three subclones derived from alpha-BAC DNA by bulk
      EMSA selection retained the ability to bind nuclear proteins of K562 cells when
      retested by EMSA. In 19 clones sequenced, 14 are identical to those registered in
      GenBank and five have one base difference. All of the 24 randomly picked beta-BAC
      clones showed specific binding with nuclear proteins of K562 cells. In 11 clones
      sequenced, eight are identical to those registered in GenBank and three have one
      base difference. This approach could be particularly powerful if combined with
      other systematic methods for identifying cis-regulatory DNA elements.

PMID- 12234095
TI  - Mammalian EGLN genes have distinct patterns of mRNA expression and regulation.
AB  - The mammalian EGLN family contains three paralagous genes (EGLN1, EGLN2, and
      EGLN3) encoding prolyl hydroxylase isoforms that mediate the oxygen-dependent
      targeting of the transcription factor hypoxia inducible factor alpha to the
      proteosome. The rat orthologue of EGLN3 (SM-20) exhibits tissue-restricted
      expression, is induced by growth factors in cultured vascular smooth muscle, and
      is up-regulated during myogenesis. To determine if all three EGLN genes are
      coordinately regulated, we examined their mRNA expression in murine tissues and
      in cultured cells. We now report that the three murine EGLN mRNAs have unique but
      overlapping patterns of tissue expression. The most striking differences were in
      the heart, where EGLN3 had its highest levels of expression, and the testis,
      where EGLN2 was the only isoform expressed. In cultured vascular smooth muscle
      cells, serum treatment led to up-regulation of EGLN1 and EGLN3, but not EGLN2,
      and only EGLN3 was superinduced by cyclohexamide. In cultured C2C12 myocytes,
      EGLN3 was up-regulated during differentiation, whereas EGLN1 and EGLN2 were
      constitutively expressed. The abundance of EGLN3 mRNA in the heart, its induction
      by growth factors in vascular smooth muscle, and its regulation during C2C12
      differentiation suggest a unique role for EGLN3 and might justify the development
      of isoformspecific inhibitors.

PMID- 12234096
TI  - Conformational changes and inactivation of rabbit muscle creatine kinase in
      dimethyl sulfoxide solutions.
AB  - The effects of dimethyl sulfoxide (DMSO) on creatine kinase (CK) conformation and
      enzymatic activity were studied by measuring activity changes, aggregation, and
      fluorescence spectra. The results showed that at low concentrations (< 65% v/v),
      DMSO had little effect on CK activity and structure. However, higher
      concentrations of DMSO led to CK inactivation, partial unfolding, and exposure of
      hydrophobic surfaces and thiol groups. DMSO caused aggregation during CK
      denaturation. A 75% DMSO concentration induced the most significant aggregation
      of CK. The CK inactivation and unfolding kinetics were single phase. The
      unfolding of CK was an irreversible process in the DMSO solutions. The results
      suggest that to a certain extent, an enzyme can maintain catalytic activity and
      conformation in water-organic mixture environments. Higher concentrations of DMSO
      affected the enzyme structure but not its active site. Inactivation occurred
      along with noticeable conformational change during CK denaturation. The
      inactivation and unfolding of CK in DMSO solutions differed from other
      denaturants such as guanidine, urea, and sodium dodecyl sulfate. The exposure of
      hydrophobic surfaces was a primary reason for the protein aggregation.

PMID- 12234097
TI  - Differential effects of a molybdopterin synthase sulfurylase (moeB) mutation on
      Escherichia coli molybdoenzyme maturation.
AB  - We have generated a chromosomal mutant of moeB (moeBA228T) that demonstrates
      limited molybdenum cofactor (molybdo-bis(molybdopterin guanine dinucleotide) (Mo
      bisMGD)) availability in Escherichia coli and have characterized its effect on
      the maturation and physiological function of two well-characterized respiratory
      molybdoenzymes: the membrane-bound dimethylsulfoxide (DMSO) reductase (DmsABC)
      and the membrane-bound nitrate reductase A (NarGHI). In the moeBA228T mutant
      strain, E. coli F36, anaerobic respiratory growth is possible on nitrate but not
      on DMSO, indicating that cofactor insertion occurs into NarGHI but not into
      DmsABC. Fluorescence analyses of cofactor availability indicate little detectable
      cofactor in the moeBA228T mutant compared with the wild-type, suggesting that
      NarGHI is able to scavenge limiting cofactor, whereas DmsABC is not. MoeB
      functions to sulfurylate MoaD, and in the structure of the MoeB-MoaD complex, Ala
      228 is located in the interface region between the two proteins. This suggests
      that the moeBA228T mutation disrupts the interaction between MoeB and MoaD. In
      the case of DmsABC, despite the absence of cofactor, the twin-arginine signal
      sequence of DmsA is cleaved in the moeBA228T mutant, indicating that maturation
      of the holoenzyme is not cofactor-insertion dependent.

PMID- 12234098
TI  - Hepatitis B viral core protein activates the hepatitis B viral enhancer
      II/pregenomic promoter through the nuclear factor kappaB binding site.
AB  - We here demonstrated that the hepatitis B viral (HBV) core protein (HBc)
      functions as a transcriptional activator on the pregenomic promoter of HBV.
      Detailed analyses on the HBV pregenomic promoter by serial deletion, mutation,
      and heterologous promoter system showed that the site responsible for activation
      was the nuclear factor kappaB (NF-kappaB) binding site (GGGACGTACT, nucleotides
      1408-1417) upstream of the enhancer II/pregenomic promoter. The electrophoretic
      mobility shift assay using the HBc-transfected HepG2 nuclear extracts showed that
      the HBc enhanced the NF-kappaB DNA-binding ability. These results suggest that
      the HBc functions as a positive regulator, which may enhance viral replication in
      hepatocytes.

PMID- 12234099
TI  - Selective inhibition of cathepsin B with cell-permeable CA074Me negatively
      affects L6 rat myoblast differentiation.
AB  - Active cathepsin B, in concert with other cellular proteases, has been implicated
      in the catabolic restructuring associated with myotube formation during skeletal
      myoblast cell differentiation (i.e., myogenesis). We have examined this role in
      differentiating myoblasts using the cell-permeable, cathepsin B selective
      inhibitor CA074Me. Cathepsin B activity levels in differentiating L6 rat
      myoblasts treated with CA074Me were significantly lower than levels in control
      myoblasts. Inhibition of cathepsin B activity by CA074Me occurred at each stage
      of differentiation and was dose related. Myotube size and number and induced
      levels of fusion-related creatine phosphokinase activity and myosin heavy-chain
      protein were reduced from 30 to 50% in CA074Me-treated myoblasts. These
      reductions were also dose related. In contrast, CA074Me did not affect levels of
      myogenin, an early marker of myogenesis, or levels of cathepsin L type and
      myokinase activities, two nonspecific enzymes. The negative effects associated
      with CA074Me were reversed when the drug was removed. Collectively, these data
      suggest that active cathepsin B plays a role in myoblast-myoblast fusion and
      consequently may be necessary for the complete expression of those genes
      associated with the fusion process.

PMID- 12234100
TI  - Acute regulation of hepatic lipase secretion by rat hepatocytes.
AB  - Hepatic lipase is involved in cholesterol uptake by the liver. Although it is
      known that catecholamines are responsible for the daily variation of enzyme
      activity, the mechanisms involved are poorly understood. Rat hepatocytes
      incubated with adrenaline or other Ca(2+)-mobilizing hormones were used as an
      experimental model. Adrenaline reduced in a similar proportion the secretion of
      both hepatic lipase and albumin. The effect of adrenaline disappeared completely
      in cells exposed to cycloheximide. Adrenaline decreased incorporation of [35S]Met
      into cellular and secreted proteins, but it affected neither degradation of
      [35S]Met-prelabeled proteins nor the abundance of total and specific (albumin,
      hepatic lipase, beta-actin) mRNA. Other Ca(2+)-mobilizing agents had the opposite
      effect on hepatic lipase secretion: it was decreased by vasopressin but was
      increased by epidermal growth factor. Vasopressin and epidermal growth factor had
      the opposite effect on [35S]Met incorporation into cellular and secreted
      proteins, but neither affected hepatic lipase mRNA. The acute effect of
      adrenaline, vasopressin, and epidermal growth factor on hepatic lipase secretion
      is the consequence of the effect of these hormones on protein synthesis and is
      therefore nonspecific.

PMID- 12234101
TI  - Expression of prolactin receptors and regulation of cell proliferation by
      prolactin, corticotropin-releasing factor, and corticosterone in a neuroblastoma
      cell line.
AB  - The aetiology of neuroblastoma remains obscure, although a number of
      neuropeptides have been implicated in its pathogenesis. Using the mouse
      neuroblastoma cell line Neuro2a as a model, we have investigated the mitogenic
      actions of prolactin (PRL) and two hypothalamo-pituitary-adrenal stress axis
      hormones, corticotropin-releasing factor (CRF) and corticosterone. Using
      established polyclonal PRL receptor antisera with immunofluorescence
      cytochemistry, we show that the Neuro2a cells possess immunoreactive forms of
      both the long and short forms of the receptor. PRL and CRF were effective as
      mitogens in Neuro2a cell cultures, where a 10(-7) M concentration of PRL or CRF
      elicited a two-fold increase in the numbers of cells after 72 h (p < 0.0001).
      Corticosterone, however, attenuated their proliferation. These data suggest that
      prolactin may act to increase the proliferation and regulation of neuroblastomas
      and that the effects of PRL may be modified by hypothalamo-pituitary-adrenal
      hormones.

PMID- 12234102
TI  - Myocardial drug distribution pattern following intrapericardial delivery: an MRI
      analysis.
AB  - OBJECTIVES: The main goal was to gain insights into the pharmacokinetics of
      intrapericardial drug delivery using magnetic resonance (MR) imaging analysis and
      the extracellular MR contrast agent gadopentetate dimeglumine (Gd-DTPA) as a
      model. BACKGROUND: Recent development of catheter-based techniques to access the
      intact pericardial space has increased interest in intrapericardial delivery for
      local cardiac therapy. Distribution and myocardial penetration of
      intrapericardial agents are not well characterized. METHODS: The intact
      pericardial space was percutaneously accessed through the right atrial appendage
      in ten anesthetized pigs, following which 5 mL Gd-DTPA (N = 8) or normal saline
      as control (N = 2) were administered. Animals were sacrificed at 1, 3, 3.5, 5, or
      8 hr. The whole heart was excised, washed with normal saline, and the chambers
      distended with saline-filled bags. Myocardial penetration of Gd-DTPA was analyzed
      by a series of short-axis T1-weighted turbospin-echo MR images. RESULTS: At 1, 3,
      and 3.5 hr after Gd-DTPA, a uniform ring of enhancement was found along the
      epicardium, with a depth density related to time after administration. No
      contrast ring was visible at 5 or 8 hr or in control animals. Transmural
      myocardial T1 values obtained 5 hr after Gd-DTPA administration were reduced,
      suggesting that Gd-DTPA had penetrated uniformly throughout the myocardium.
      CONCLUSIONS: Intrapericardial administration results in relatively uniform
      distribution of an agent across the ventricular epicardium. The depth of
      penetration is consistent with functional evidence that epicardial structures can
      be targeted by this technique.

PMID- 12234103
TI  - Left ventricular remodeling subsequent to reperfused myocardial infarction:
      evaluation of a rat model using cardiac magnetic resonance imaging.
AB  - PURPOSE: This study characterized the time course of ventricular remodeling
      subsequent to reperfused myocardial infarction (MI) in a rat model using cardiac
      magnetic resonance (MR) imaging. METHODS AND RESULTS: Short axis cine MR imaging
      was used to measure left ventricular ejection fraction (LVEF) and left
      ventricular volumes in Lewis rats at baseline, 1, 2, 4, 6, 8, and 10 weeks post
      MI. Ventricular pressure and myocardial mass were evaluated at the 10 week time
      point. RESULTS: Measurements of LVEF showed a significant decrease in cardiac
      function immediately after MI with no significant changes over the remainder of
      the time course. Measurements of left ventricular end-systolic volume (LVESV)
      showed significant increases over thefirst 4 weeks after MI with no significant
      changes over the remainder of the time course. Statistical analysis of the MR
      measurements of LVESV yielded a repeatability standard error of 3.3%, an inter
      observer standard error of 3.3%, and an intra-observer standard error of 1.6%.
      CONCLUSION: This study indicates that cine MRI can be used to longitudinally
      evaluate changes in ventricular structure and function in a rat model of left
      ventricular remodeling. In this animal model, preliminary results indicate that
      the majority of remodeling is completed by 4 weeks and no significant changes in
      LVEF are seen after the first week. The repeatability values indicate that
      cardiac MR could be used for evaluating new therapies for mitigating the effects
      of LV remodeling after reperfused MI.

PMID- 12234104
TI  - Improved accuracy of quantitative assessment of left ventricular volume and
      ejection fraction by geometric models with steady-state free precession.
AB  - The purpose of this study was to determine whether steady-state free precession
      (SSFP) could improve accuracy of geometric models for evaluation of left
      ventricular (LV) function in comparison to turbo gradient echo (TGrE) and thereby
      reduce the acquisition and post-processing times, which are commonly long by use
      of the Simpson's Rule. In 25 subjects, cine loops of the complete heart in short
      and horizontal long-axis planes were acquired using TGrE (TR/TE/flip =
      5.0/1.9/25) compared with SSFP (TR/TE/flip = 3.2/1.2/60). LV volumes and EF were
      measured with various geometric models for TGrE and SSFP. With three-dimensional
      data, the LV volumes were higher and the resulting EF lower for SSFP in contrast
      to TGrE (51 +/- 15% vs. 57 +/- 15%, p < 0.001). With SSFP, various geometric
      models yielded good to excellent correlations for LV volumes and LVEF compared to
      volumetric data (r = 0.94-0.98, mean relative difference 7.0-11.4%). In contrast,
      correlations were low using biplane or single-plane ellipsoid models in TGrE (r =
      0.71-0.75, mean relative difference 15.9-30.2%). A new combined geometric model,
      taking all three dimensions into account, yielded the highest accuracy for SSFP
      in comparison to volumetric data (r = 0.99, mean relative difference 4.7%).
      Geometric models for assessment of LV volumes and EF yield higher accuracy and
      reproducibility by use of the SSFP sequence than by standard TGrE. This may
      increase clinical utility of magnetic resonance by shorter acquisition and
      processing times.

PMID- 12234105
TI  - Three-dimensional myocardial strains at end-systole and during diastole in the
      left ventricle of normal humans.
AB  - This paper presents the three-dimensional strains in the normal human left
      ventricle (LV) at end-systole and during diastole. Magnetic resonance tissue
      tagging was used to measure strain in the left-ventricular heart wall in 10
      healthy volunteers aged between 28 and 61 years. The three-dimensional motion was
      calculated from the displacement of marker points in short- and long-axis cine
      images, with a time resolution of 30 msec. Homogeneous strain analysis of small
      tetrahedrons was used to calculate deformation in 18 regions of the LV over a
      time span of 300 msec starting at end systole. End-systolic radial strain was
      largest near the heart base, and circumferential and longitudinal strains were
      largest near the apex. During diastole, the circumferential-longitudinal shear
      strain (associated with LV torsion) was found to recover earlier than the axial
      strains. Assessment of three-dimensional diastolic strain is possible with MR
      tagging. Comparison of patient strain against normal strain may permit early
      detection of regional diastolic dysfunction.

PMID- 12234106
TI  - Noninvasive and invasive evaluation of noncompaction cardiomyopathy.
AB  - Noncompaction cardiomyopathy is a recently described rare congenital
      cardiomyopathy; patients can be asymptomatic or develop diastolic and/or systolic
      left ventricular dysfunction with heart failure, systemic emboli or ventricular
      arrhythmias. Long-term prognosis is poor. Currently, diagnosis is based on
      findings on 2D echocardiography; in the current case report we demonstrate the
      use of MRI to diagnose noncompaction cardiomyopathy.

PMID- 12234107
TI  - Coronary magnetic resonance angiography for assessment of the stent lumen: a
      phantom study.
AB  - PURPOSE: To evaluate the feasibility of visualizing the stent lumen using
      coronary magnetic resonance angiography in vitro. MATERIAL AND METHODS: Nineteen
      different coronary stents were implanted in plastic tubes with an inner diameter
      of 3 mm. The tubes were positioned in a plastic container filled with gel and
      included in a closed flow circuit (constant flow 18 cm/sec). The magnetic
      resonance images were obtained with a dual inversion fast spin-echo sequence. For
      intraluminal stent imaging, subtraction images were calculated from scans with
      and without flow. Subsequently, intraluminal signal properties were objectively
      assessed and compared. RESULTS: As a function of the stent type, various degrees
      of in-stent signal attenuation were observed. Tantalum stents demonstrated
      minimal intraluminal signal attenuation. For nitinol stents, the stent lumen
      could be identified, but the intraluminal signal was markedly reduced. Steel
      stents resulted in the most pronounced intraluminal signal voids. CONCLUSIONS:
      With the present technique, radiofrequency penetration into the stents is
      strongly influenced by the stent material. Thesefindings may have important
      implicationsforfuture stent design and stent imaging strategies.

PMID- 12234108
TI  - MRI of congenital heart disease: a paradigm of collaboration. new suggestions for
      a team approach from Madigan Army Medical Center.
AB  - Over the past decade, there has been increasing use of cardiac MRI in the
      evaluation of children with congenital heart disease. There has also been an
      increased number of radiologists and pediatric cardiologists desiring to perform
      cardiac MRI in the evaluation of these patients. At the present time, the number
      of pediatric cardiologists and radiologists fully trained in the use of MRI
      studies for CHD is inadequate to provide this modality at all institutions with
      MRI capabilities. This article describes the collaborative approach between
      pediatric cardiology and radiology at Madigan Army Medical Center and its
      implications for patient care and credentialing.

PMID- 12234109
TI  - Double-chambered right ventricle or sub-infundibular stenosis assessed by
      cardiovascular magnetic resonance.
AB  - This paper presents magnetic resonance findings in four adults with double
      chambered right ventricle or sub-infundibular stenosis, a condition that is
      treatable by surgery, but which can be difficult to assess echocardiographically.
      Four patients referred for cardiovascular magnetic resonance in the last 2 years
      were identified from CMR findings, although not necessarily from previous
      echocardiography, as having sub-infundibular stenosis. We used multislice spin
      echo imaging, cine imaging in oblique sagittal planes, and phase velocity
      mapping. We performed spin echo imaging of a post-mortem heart without known
      structural abnormality to illustrate right ventricular myocardial morphology.
      Results in patients showed evidence of sub-infundibular muscular obstruction
      separating the hypertrophied inlet and apical portions of the right ventricle
      from a thin-walled, unobstructed infundibular region in each case, with a
      systolic jet originating at least 15 mm beneath the unstenosed pulmonary valve.
      In addition to previously described structural components contributing to
      stenosis--enlargement and/or displacement of the septomarginal trabeculation,
      septoparietal trabeculations or the moderator band--CMR suggested additional
      components: a right ventricular papillary muscle in one, an anteriorly bulging
      aortic sinus in one, and hypertrophied muscular ridges of the parietal wall of
      the right ventricle. Even in this small group of patients, the causes of sub
      infundibular stenosis appeared to be varied and multi-factorial. The abilities of
      magnetic resonance to give unrestricted, multi-planar views of right ventricular
      anatomy, movement and flow make it well suited for diagnosis and characterization
      of sub-infundibular stenosis, especially in adults.

PMID- 12234110
TI  - The assessment of myocardial viability: a review of current diagnostic imaging
      approaches.
AB  - The management of patients with coronary artery disease, both in the post
      infarction setting, and in patients with chronic advanced left ventricular (LV)
      dysfunction, is complicated by the presence of both reversibly damaged and
      infarcted myocardium. Although acute revascularization with thrombolytic therapy
      and percutaneous angioplasty have served to reduce the overall mortality from
      myocardial infarction, the ability to predict whether or not dysfunctional
      myocardium will recoverfollowing revascularization presents the clinician with a
      serious challenge. The success of revascularization, both on improvement of LV
      function, and short and long-term prognosis, depends on both the existence and
      extent of viable but dysfunctional myocardium present, as there is little to be
      gained from revascularizing a territory consisting exclusively of scar. There is
      a clear demand for procedures that can identify reversible asynergy prospectively
      and thus deliver the information that is needed for clinical decision-making. The
      objective of this review is to summarize the diagnostic tools that are currently
      availablefor the identification of reversible injury (ie., stunned or hibernating
      myocardium). The relative merits of echocardiography, nuclear medicine imaging,
      and magnetic resonance imaging are discussed in detail. Within the discussion of
      each modality, special attention is paid to the more recent innovations that have
      arisen to enhance the diagnostic and prognostic value of older approaches. Cost,
      availability, and local expertise will always affect the clinical popularity of a
      given diagnostic approach. However, the overriding conclusion that emerges from
      this review is that the future "techniques of choice" will be those that can
      reliably predict and quantify the extent of potential functional recovery.

PMID- 12234111
TI  - 3T or not 3T, that is the question.

PMID- 12234112
TI  - Model of spike propagation reliability along the myelinated axon corrupted by
      axonal intrinsic noise sources.
AB  - We investigated how selected electromorphological parameters of myelinated axons
      influence the preservation of interspike intervals when the propagation of action
      potentials is corrupted by axonal intrinsic noise. Hereby we tried to determine
      how the intrinsic axonal noise influences the performance of axons serving as
      carriers for temporal coding. The strategy of this coding supposes that
      interspike intervals presented to higher order neurons would minimally be
      deprived of information included in interspike intervals at the axonal initial
      segment. Our experiments were conducted using a computer model of the myelinated
      axon constructed in a software environment GENESIS (GEneral NEural SImulation
      System). We varied the axonal diameter, myelin sheath thickness, axonal length,
      stimulation current and channel distribution to determine how these parameters
      influence the role of noise in spike propagation and hence in preserving the
      interspike intervals. Our results, expressed as the standard deviation of spike
      travel times, showed that by stimulating the axons with regular rectangular
      pulses the interspike intervals were preserved with a microsecond accuracy.
      Stimulating the axons with pulses imitating postsynaptic currents, greater
      changes of interspike intervals were found, but the influence of implemented
      noise on the jitter of interspike intervals was approximately the same.

PMID- 12234113
TI  - Inhibition of beta-1 receptor but not vagotomy can abolish the L-NAME evoked
      bradycardia in anesthetized rat.
AB  - We reported previously that the nitric oxide synthesis inhibitor N(omega)-nitro-L
      arginine methyl ester (L-NAME) decreases cardiac output. Several studies have
      shown that inhibition of nitric oxide synthesis decreases the heart rate. In the
      present study, we investigated the effect of a single bolus administration of L
      NAME on blood pressure and heart rate monitored for one hour in anesthetized rats
      and the influence of vagotomy and beta1-receptor blocker metoprolol on the L-NAME
      induced bradycardia. After L-NAME treatment, the blood pressure rose immediately
      after the injection of the drug (peak response in the third minute: +24%,
      p<0.001) and fell to the control level in the 20th minute. The heart rate
      decreased immediately after L-NAME administration, the lowest value being reached
      in the 10th minute (-14%, p<0.001). However, bradycardia was sustained even after
      the blood pressure had returned to the control level. Bilateral vagotomy failed
      to influence the negative chronotropic effect of L-NAME, but bradycardia was
      completely abolished by metoprolol pretreatment. We concluded that the
      bradycardia evoked by L-NAME is mainly due to the withdrawal of sympathetic tone
      upon the heart rate. However, the cause of sustained bradycardia after
      normalization of blood pressure cannot be elucidated.

PMID- 12234114
TI  - Do the oscillations of cardiovascular parameters persist during voluntary apnea
      in humans?
AB  - The aim of this study was to ascertain the persistence of heart rate and blood
      pressure oscillations at the onset of voluntary apnea in humans and to assess the
      dependence of the fluctuations parameters on the chemoreceptor activity. In 24
      young subjects (10 males, 14 females, mean age 20.4 years) heart rate
      (represented by its reciprocal value--RR-intervals), systolic blood pressure
      (SBP) and diastolic blood pressure (DBP) during controlled breathing (CB) of
      atmospheric air and oxygen followed by apnea were recorded continuously. The
      cosine functions were then fitted by nonlinear regression analysis to the heart
      rate, SBP and DBP oscillations during CB and at the onset of apnea. The
      parameters of oscillations were different during atmospheric air breathing
      compared to oxygen breathing. During oxygen breathing there was an increase of
      the RR-interval oscillations--relative bradycardia and enhanced magnitude of
      respiratory sinus arythmia. During apnea, the base level of the blood pressure
      oscillations was higher after breathing of atmospheric air compared to oxygen
      breathing. At least one cosine-like wave oscillation was present at the onset of
      apnea in the heart rate, SBP and DBP and the second wave was present in all
      assessed parameters in at least 70% of recordings. The oscillations in RR
      intervals are, to some extent, independent of blood pressure oscillations. No
      significant gender differences were found either in the duration of breath
      holding or in the RR and SBP oscillations parameters.

PMID- 12234115
TI  - Clarithromycin inhibits myometrial contractions in isolated human myometrium
      independent of stimulus.
AB  - Erythromycin has a well-known dual effect on the contractility of the
      gastrointestinal system and recently has also been shown to inhibit contractions
      of the rat myometrium. The aim of the present study was to investigate the
      effects of clarithromycin on oxytocin, prostaglandin F2alpha (PGF2alpha) and KCl
      induced contractions of human myometrium in vitro. Myometrial strips were
      obtained from pregnant women undergoing elective Cesarean section and the strips
      were suspended in a jacketed organ bath filled with Krebs solution at 37 degrees
      C (pH 7.4) and continuously aired with 95% oxygen and 5% carbon dioxide.
      Isometric contractions were measured using a force displacement transducer.
      Oxytocin, PGF2alpha, KCl and clarithromycin were applied to the tissue bath and
      the amplitude and frequency of contractions were evaluated at 20-min intervals.
      Freidmann analysis of variance, Kruskal Wallis and Wilcoxon Rank tests were used
      for statistical analysis of the data. Clarithromycin dose dependently inhibited
      the amplitude of contractions independent of the stimulus. Pre-treatment with
      apamin prevented clarithromycin-induced effects on amplitude and frequency of
      contractions. We conclude that the macrolide antibiotic clarithromycin may have a
      direct inhibitory effect on contractions of human myometrium.

PMID- 12234117
TI  - Streptozotocin induces lipolysis in rat adipocytes in vitro.
AB  - Streptozotocin (STZ) is used to induce experimental diabetes in animals and is
      also applied for the treatment of patients with insulinoma. The aim of the
      present work was to investigate the direct effect of STZ on lipolysis in isolated
      rat adipocytes. After the isolation, the cells were incubated in a Krebs-Ringer
      buffer of pH 7.4, at the temperature 37 degrees C for 90 min with different
      concentrations of STZ: 0.5, 1 or 2 mmol/l. STZ caused a significant rise in basal
      values (99%, 199%, and 377%, respectively) and epinephrine-stimulated (1
      micromol/l) lipolysis (15%, 24% and 46%, respectively). Augmentation of basal
      lipolysis by STZ was neither restricted by insulin (1 nmol/l) nor by H-89 (an
      inhibitor of protein kinase A, 50 micromol/l). These results indicate the
      stimulatory influence of STZ on the action of hormone-sensitive lipase in
      isolated cells of white adipose tissue. The obtained outcomes suggest that in
      studies employing STZ, it is necessary to consider its direct effect upon
      lipolysis in adipocytes.

PMID- 12234116
TI  - Effects of exercise on muscle metabolites and sarcoplasmic reticulum function in
      ovariectomized rats.
AB  - The relationships between exercise and metabolites as well as between exercise
      and sarcoplasmic reticulum function were studied in gastrocnemius muscle of
      ovariectomized-trained rats. Prolonged moderate-intensity exercise, treadmill up
      hill run for 90 min with a 10 degree incline, decreased the muscle glycogen
      content. Exercise until exhaustion further lowered the glycogen concentration to
      13% of the control, together with a significant decrease of ATP and glucose-6
      phosphate concentrations. Also, Ag+-induced Ca2+ release, measured in whole
      muscle homogenate, showed a 30% reduction on exhaustion, while Ca2+ uptake was
      unaffected by this exercise. ATPase activities, of both homogenate and SR
      vesicles, and Ca2+ transport in the latter preparation were not altered on
      exhaustion. It could be concluded from these results that muscular fatigue in
      ovariectomized rats after aerobic exercise is caused by the change in energy
      supply and Ca2+ release from the SR, this latter possibly due to metabolites
      generated by the exercise.

PMID- 12234118
TI  - Effect of hypothermia on insulin-receptor interaction in different rat tissues.
AB  - Experimental hypothermia caused extensive changes in the number of both classes
      of insulin receptors in different rat tissues. In the liver, the number of high
      affinity insulin receptors (HAIRs) decreased by 50% (from 25.3 to 12.6 fmol/mg
      membrane protein), whereas number of low affinity insulin receptors (LAIRs) was
      almost unchanged in comparison to normothermic animals (5.63 and 4.39 pmol/mg,
      respectively). In the adipose tissue, number of both classes was reduced--HAIRs
      by 81% (from 24.0 to 4.50 fmol/mg) and LAIRs by 92% (from 16.0 to 1.29 pmol/mg).
      In the skeletal muscle, capacity of HAIRs was not changed (16.2 and 19.3 fmol/mg
      in normo- and hypothermic animals, respectively), whereas number of LAIRs
      increased by 150% (from 6.65 to 16.6 pmol/mg). Hypothermic rats also showed lower
      amount (by 85%) of LAIRs in the heart muscle (9.37 and 1.43 pmol/mg in control
      and experimental animals, respectively). Simultaneously, no significant changes
      were found in HAIRs (16.3 and 11.9 fmol/mg, respectively) and LAIRs (4.43 and
      3.88 pmol/mg, respectively) in the brain. These differences in insulin receptors
      responses to hypothermia may reflect different physiological role of insulin in
      the regulation of target cell metabolism and/or the differences in tissue
      distribution of the insulin receptor isoforms.

PMID- 12234119
TI  - Sensitivity and specificity of the bioassay of estrogenicity in mammary gland and
      seminal vesicles of male mice.
AB  - Young intact (18 days old) and adult castrated males of CBA and C3H/Di mice were
      used for measuring the estrogenicity on the basis of growth response of mammary
      epithelial structures and the weight of seminal vesicles. It was demonstrated
      that heavier young males had disproportionally heavier seminal vesicles (sex
      steroid-responsive organs) than small animals at day 33 of age (that is on the
      day when experimental animals were killed and organs dissected). However, the
      weight of the spleen (sex steroid-nonresponsive organ) was proportionally related
      to body weight. To minimize variability in hormone responsiveness, all animals
      were weighed at the age of 18 days and only males weighing 8+/-1 g were used for
      hormone treatment. The percentage area of mammary fat pad occupiedby mammary
      epithelial structures was progressively increased by 17beta estradiol from dose
      0.01 microg x d(-1). The maximum effective dose of estradiol was 0.1 microg x d(
      1) and dose 10 microg x d(-1) of estradiol decreased mammary size to control
      level (inverted-U-shaped dose-response curve). Progesterone alone stimulated
      mammary growth only in high doses (500 microg x d(-1) and higher) in young intact
      males, but had no effect on mammary growth in adult castrated animals. In young
      intact males, estradiol alone, or progesterone alone decreased the weight of
      seminal vesicles. No such inhibitory effect of these hormones was noted in adult
      castrated males. Progesterone acted synergistically with estradiol to produce
      higher mammary growth compared to that in males treated with estradiol alone. In
      the presence of progesterone seminal vesicles weight was decreased by estradiol
      given in such low doses as 0.001 microg x d(-1) of estradiol, which is 10 times
      lower than that effective in animals treated with estradiol alone. On the other
      hand, in the adult castrated males a combination of estradiol plus progesterone
      stimulated seminal vesicles weight. The effects of a combination of estradiol
      plus progesterone in the mammary gland were mimicked by norethindrone acetate (a
      synthetic steroid exhibiting progestantial and estrogenic activities) and
      inhibited by both testosterone and cortisol. Estradiol, progesterone,
      norethindrone acetate, or testosterone did not affect spleen weight and size of
      mammary lymph nodes.However, cortisol significantly decreased not only spleen
      weights but also size of mammary lymph nodes. These results showthat simultaneous
      evaluation of mammary gland growth, seminal vesicles, and the spleen weight in
      the same animal is suitable for bioassay of estrogenicity as well as for
      detection of androgenic and antiandrogenic activities.

PMID- 12234121
TI  - Protective effects of topical alpha-tocopherol acetate on UVB irradiation in
      guinea pigs: importance of free radicals.
AB  - Reactive oxygen species can be generated by daily exposure of the skin to
      ultraviolet light and may cause some subchronic and chronic skin disorders. The
      aim of this study was to investigate a possible preventive role of alpha
      tocopherol acetate (ATA) on ultraviolet B (UVB) induced peroxidation by assessing
      lipid peroxide (LPO) levels and activity of reactive oxygen scavenging enzymes
      including glutathione peroxidase and superoxide dismutase (SOD) in guinea pigs.
      ATA was topically applied to the skin for three weeks before a single dose of 0.9
      J/cm2 UVB irradiation on the skin and lipid peroxide levels and antioxidants in
      plasma, skin and liver and erythrocytes were determined after decapitation.
      Topical application of ATA prevented the UVB irradiation-induced reduction of
      scavenging enzyme activities in skin and erythrocytes. In conclusion, we suggest
      that topical applications of ATA before UVB irradiation is effective in
      protecting the skin from unwanted effects of UVB irradiation.

PMID- 12234120
TI  - Influence of beta-resorcylidene aminoguanidine on selected metabolic parameters
      and antioxidant status of rats with diabetes mellitus.
AB  - We studied the effects of administration of beta-resorcylidene aminoguanidine
      (RAG) to Wistar strain rats with experimental diabetes mellitus (DM) induced by
      streptozotocin. The effects studied included antioxidant levels in plasma and the
      liver, oxidative damage of lipids represented by the formation of substances
      reacting with thiobarbituric acid (TBARP) and selected biochemical indicators.
      The administration of RAG did not significantly affect antioxidant status of
      diabetic rats or hemoglobin glycation and plasma concentration of fructosamine.
      In diabetic rats, application of RAG decreased formation of TBARP in plasma but
      not in the liver. Moderate steatosis of liver and increased plasma levels of
      triacylglycerols in diabetic rats were significantly improved by application of
      RAG.

PMID- 12234122
TI  - Comparative study of several lymphocyte functions in two strains of mice with
      different models of endotoxic shock.
AB  - Previously, the changes in phagocyte functions such as adherence, chemotaxis or
      TNFalpha production were found to be associated with oxidative stress in
      endotoxin-induced septic shock. However, in this type of oxidative stress the
      lymphocyte involvement has rarely been studied. In the present report, we
      analyzed the above functions in peritoneal lymphocytes from male and female
      BALB/c mice with a lethal endotoxic shock caused by intraperitoneal injection of
      E. coli lipopolysaccharide (LPS) (100 mg/kg), male and female Swiss mice with
      lethal endotoxic shock caused by intraperitoneal injection of LPS (150 and 250
      mg/kg, respectively) or non-lethal endotoxic shock (100 mg/kg). In peritoneal
      lymphocytes obtained at 0, 2, 4, 12 or 24 h after LPS injection, the first two
      functions of these cells in the immune response, i.e. adherence to tissues and
      directed migration (chemotaxis), were studied. At 0, 0.5, 1, 1.5, 2, 4, 12 and 24
      h after LPS injection, TNFalpha released by lymphocytes was also analyzed. The
      results show that endotoxic shock increases the adherence and TNFalpha release,
      and decreases the chemotaxis of peritoneal lymphocytes. These changes were more
      significant in mice with lethal than with non-lethal endotoxic shock, a fact that
      confirms the important role of lymphocytes during endotoxic shock.

PMID- 12234123
TI  - Nitric oxide synthase inhibition and glutamate binding in quinolinate-lesioned
      rat hippocampus.
AB  - The effect of lesions induced by bilateral intracerebroventricular (i.c.v.)
      injection of quinolinate (250 nmol of QUIN/ventricle), a selective N-methyl-D
      aspartate (NMDA) receptor agonist, on [3H]glutamate ([3H]Glu) binding to the main
      types of both ionotropic and metabotropic glutamate receptors (iGluR and mGluR)
      was investigated in synaptic membrane preparations from the hippocampi of 50-day
      old rats. The membranes from QUIN injured brains revealed significantly lowered
      binding in iGluR (by 31%) as well as in mGluR (by 22%) as compared to the
      controls. Using selected glutamate receptor agonists as displacers of [3H]Glu
      binding we found that both the NMDA-subtype of iGluR and group I of mGluR are
      involved in this decrease of binding. Suppression of nitric oxide (NO) production
      by N(G)-nitro-L-arginine (50 nmol of NARG/ventricle) or the increase of NO
      generation by 3-morpholinylsydnoneimine (5 nmol of SIN-1/ventricle) failed to
      alter [3H]Glu or [3H]CPP (3-((D)-2-carboxypiperazin-4-yl)-[1,2-(3)H]-propyl-1
      phosphonic acid; NMDA-antagonist) binding declines caused by QUIN-lesions. Thus,
      our findings indicate that both the NMDA-subtype of iGluR and group I of mGluR
      are susceptible to the QUIN-induced neurodegeneration in the rat hippocampus.
      However, the inhibition of NO synthesis did not reveal any protective action in
      the QUIN-evoked, NMDA-receptor mediated decrease of [3H]Glu binding. Therefore,
      the additional mechanisms of QUIN action, different from direct NMDA receptor
      activation/NO production (e.g. lipid peroxidation induced by QUIN-Fe-complexes)
      cannot be excluded.

PMID- 12234124
TI  - Measurement of leptin and insulin-like growth factor-I in seminal plasma from
      different species.
AB  - The multi-functional proteins, insulin-like growth factor-I (IGF-I) and leptin
      were present in seminal plasma from different species. Concentrations of IGF-I in
      equine and porcine semen were 20 and 17.5 ng/ml, respectively. Seminal plasma
      concentrations of leptin were 1 ng/ml in human and 11 ng/ml in porcine samples.

PMID- 12234125
TI  - Advanced glycation end products and nutrition.
AB  - Advanced glycation end products (AGEs) may play an important adverse role in
      process of atherosclerosis, diabetes, aging and chronic renal failure. Levels of
      N(epsilon)-carboxymethyllysine and fluorescent AGE values were estimated in two
      nutritional population groups--alternative group (vegetarians--plant food, milk
      products, eggs) and traditional group (omnivorous subjects). Vegetarians have a
      significantly higher carboxymethyllysine content in plasma and fluorescent AGE
      values. Intake of proteins, lysine and monosaccharides as well as culinary
      treatment, consumption of food AGEs (mainly from technologically processed
      products) and the routes of Maillard reaction in organism are the substantial
      sources of plasma AGEs. Vegetarians consume less proteins and saccharides. Lysine
      intake is significantly reduced (low content in plant proteins). Subjects on
      alternative nutrition do not use high temperature for culinary treatment and
      consume low amount of technologically processed food. Fructation induced AGE
      fluorescence is greater as compared with that induced by glucose. It is due to
      higher participation of a more reactive acyclic form of fructose. Intake of
      vegetables and fruit with predominance of fructose is significantly higher in
      vegetarians. Comparison of nutrition and plasma AGEs in vegetarian and omnivorous
      groups shows that the higher intake of fructose in alternative nutrition of
      healthy subjects may cause an increase of AGE levels.

PMID- 12234126
TI  - Citalopram inhibits L-type calcium channel current in rat cardiomyocytes in
      culture.
AB  - Selective serotonine reuptake inhibitors (SSRI) are believed to be less dangerous
      in the treatment of depressive disorder in comparison with tricyclic
      antidepressants (TCA) due to their relative lack of cardiotoxicity. Thus, we
      investigated the effect of citalopram (SSRI) on membrane electrophysiology in rat
      cardiomyocytes in tissue culture. The results were compared with those from
      amitriptyline (TCA). The whole-cell configuration patch-clamp technique was used.
      Both citalopram and amitriptyline exhibited the concentration-dependent
      inhibition of the L-type calcium channel current (ICa). Citalopram in
      concentrations of 3 microM and 10 microM inhibited peak calcium current by 2.7%
      and 8%, respectively. We demonstrated the same potency of citalopram and
      amitriptyline to inhibit ICa. These observations led us to conclude that
      citalopram and amitriptyline are drugs, which exhibit a similar potency for
      causing concentration-dependent inhibition of ICa.

PMID- 12234127
TI  - Tuberculosis and poverty.

PMID- 12234128
TI  - NRAMP1 and susceptibility to tuberculosis.

PMID- 12234129
TI  - Quality assurance programme for drug susceptibility testing of Mycobacterium
      tuberculosis in the WHO/IUATLD Supranational Reference Laboratory Network: five
      rounds of proficiency testing, 1994-1998.
AB  - SETTING: Quality assurance for the WHO/IUATLD Global Tuberculosis Drug Resistance
      Surveillance Programme. OBJECTIVE: To implement an ongoing proficiency-testing
      programme for drug susceptibility testing (DST) of Mycobacterium tuberculosis
      within the WHO/IUATLD Supranational Reference Laboratories Network (SRLN).
      DESIGN: Five culture panels, each consisting of 10 duplicate drug-susceptible and
      drug-resistant clinical isolates (100 strains) of M. tuberculosis were tested for
      resistance to streptomycin (SM), isoniazid (INH), rifampicin (RMP) and ethambutol
      (EMB). DST procedures included the proportion, absolute concentration and
      resistance ratio methods, as well as the radiometric BACTEC 460 method. RESULTS:
      The efficiency, sensitivity and specificity of M. tuberculosis DST as well as the
      intra-laboratory reproducibility showed that the laboratories tested
      susceptibility to RMP and to INH very reliably, with values ranging from 97% to
      99%. The testing of SM and EMB was less dependable, with values ranging from 90%
      to 95%. The sensitivity of testing of EMB increased from 60% in Round 1 to 98% in
      Round 5, without a concomitant decrease in specificity. CONCLUSIONS: This study
      has shown that regular proficiency testing can significantly improve the quality
      of DST, even in the most sophisticated TB laboratories. Mean DST efficiency
      levels of 92% for both SM and EMB and 97% and 99% for INH and RMP, respectively,
      are proposed as reasonable performance goals for the SRL network. Efficiency,
      consistently lower than these values, would require remedial action. Efficiency
      levels lower than mean -1 standard error, i.e., 80% for SM and EMB, 89% for INH
      and 95% for RMP, should always be considered as sub-standard performance for DST.

PMID- 12234130
TI  - Anti-tuberculosis drug resistance in community and prison patients, Orel Oblast,
      Russian Federation.
AB  - SETTING: Orel Oblast, Russian Federation. OBJECTIVES: To determine baseline
      levels of anti-tuberculosis drug resistance in Orel Oblast. DESIGN: Drug
      susceptibility testing (DST) records from 1 July 1999 to 30 June 2000 for
      patients with sputum acid-fast bacilli smear-positive pulmonary tuberculosis were
      reviewed. Treatment and incarceration status were obtained from the tuberculosis
      register. Patients with 1 month or less of prior treatment were defined as new
      cases; those previously treated for more than 1 month were defined as retreatment
      cases. RESULTS: Of 246 smear-positive isolates, 212 (86%) had DST performed. Of
      these, 190 (90%) were from new and 22 (10%) from retreatment cases; 171 (81%)
      were from community and 41 (19%) were from prison patients. Any drug resistance
      was more common among prison than community patients (44% vs. 30%, P = 0.05). MDR
      TB was found in 14 (6.6%) of 212 isolates, and was more prevalent in prison
      compared with community patients (12% vs. 5%, P = 0.05). Retreatment cases were
      more likely than new cases to have MDR-TB (prevalence ratio [PR] = 8.5, 95%CI =
      3.3-22.3), although the PR was higher for prison than for community retreatment
      cases (10.0 vs. 5.8). CONCLUSIONS: New cases with MDR-TB were less prevalent in
      Orel Oblast compared with other survey sites in Russia. Any drug resistance and
      MDR-TB were associated with prior treatment, especially in the prison population.
      Continued monitoring of trends in drug resistance following DOTS implementation
      is needed.

PMID- 12234131
TI  - Efficacy of common antiseptics against multidrug-resistant Mycobacterium
      tuberculosis.
AB  - OBJECTIVES: The incidence of infections caused by multidrug-resistant strains of
      Mycobacterium tuberculosis (MDR-TB) has been increasing. Antiseptics are
      frequently used to prevent mycobacterial infection. The aim of this study was to
      determine those antiseptics that are useful against MDR-TB. DESIGN: We evaluated
      bactericidal activity against clinical isolates of MDR-TB in vitro. METHOD:
      Thirteen strains of MDR-TB were tested against povidone-iodine (PVP-I), cresol,
      akyldiaminoethyl glycine hydrocloride (AEG), and glutaraldehyde. After bacilli
      were exposed to the antiseptic solution with 2% human serum, the disinfectant was
      inactivated by addition of neutraliser. RESULTS: PVP-1 at a final concentration
      of 0.2% killed all of the strains within 120 seconds, and PVP-I at 0.1% killed
      99.9% or more bacilli within 60 seconds. Most strains were killed after exposure
      to 0.5% cresol at 300 seconds and to 1.0% cresol at 60 seconds; 3.0% cresol
      killed all bacilli within 120 seconds, while 0.1%, 0.2%, and 0.5% AEG all
      required 60 minutes to kill 99.9% or more of the bacilli; 2.0% glutaraldehyde
      required 10 minutes to kill all bacilli. CONCLUSION: The bactericidal activities
      of antiseptics for MDR-TB were similar to those for drug-sensitive M.
      tuberculosis strains. PVP-I would be a useful antiseptic against MDR-TB. The
      bactericidal activities of glutaraldehyde are effective against MDR-TB as an
      antiseptic for medical equipment.

PMID- 12234132
TI  - Tuberculosis in the elderly in Hong Kong.
AB  - BACKGROUND: The rate of tuberculosis in Hong Kong has declined dramatically since
      the 1950s, but has remained high during the past decade, at around 110/100,000.
      The reason for the persistent high rate is not clear. OBJECTIVES: To study the
      trend of tuberculosis in Hong Kong during the past decade (1989 to 1998) and the
      clinical characteristics of tuberculosis patients > or = 60 years of age, and
      compare them with those of the younger age groups. METHODS: Notification rates of
      tuberculosis from 1989 to 1998 were obtained from the Hong Kong Government
      Tuberculosis and Chest Service (Chest Service), Department of Health, Hong Kong.
      In addition, all patients registered at the Chest Service for treatment of
      tuberculosis in 1996 were studied. RESULTS: During the past decade, the
      notification rate of tuberculosis, which included both bacteriologically
      confirmed and clinically active but bacteriologically not confirmed cases,
      decreased in those under 60, remained unchanged in those between 60-69, and
      increased in those > or = 70 years of age. An increase in the rate of
      bacteriologically confirmed cases (sputum smear or culture positive for
      Mycobacterium tuberculosis) in the older age groups was observed during the same
      period. In 1989, 31.9% of tuberculosis cases were over the age of 60 years; this
      proportion increased to 45.4% in 1998. The increase in the number of cases in
      those > or = 60 years could almost account for the total increase in number of
      cases during the last decade. Patients in the older age groups had more advanced
      disease at the time of diagnosis, and a higher proportion had comorbid illnesses.
      They also had significantly higher mortality compared with the younger age
      groups. CONCLUSION: The increasing longevity of the population and the high rate
      of tuberculosis in the elderly are important factors contributing to the
      persistent high rate of tuberculosis in Hong Kong in the past decade.

PMID- 12234133
TI  - Risk factors associated with default, failure and death among tuberculosis
      patients treated in a DOTS programme in Tiruvallur District, South India, 2000.
AB  - OBJECTIVE: To identify risk factors associated with default, failure and death
      among tuberculosis patients treated in a newly implemented DOTS programme in
      South India. DESIGN: Analysis of all patients registered from May 1999 through
      April 2000. A community survey for active tuberculosis was underway in the area;
      patients identified in the community survey were also treated in this programme.
      RESULTS: In all, 676 patients were registered during the period of the study.
      Among new smear-positive patients (n = 295), 74% were cured, 17% defaulted, 5%
      died and 4% failed treatment. In multivariate analysis (n = 676), higher default
      rates were associated with irregular treatment (adjusted odds ratio [AOR] 4.3;
      95%CI 2.5-7.4), being male (AOR 3.4; 95%CI 1.5-8.2), history of previous
      treatment (AOR 2.8; 95%CI 1.6-4.9), alcoholism (AOR 2.2; 95%CI 1.3-3.6), and
      diagnosis by community survey (AOR 2.1; 95%CI 1.2-3.6). Patients with multidrug
      resistant tuberculosis (MDR-TB) were more likely to fail treatment (33% vs. 3%; P
      < 0.001). More than half of the patients receiving Category II treatment who
      remained sputum-positive after 3 or 4 months of treatment had MDR-TB, and a large
      proportion of these patients failed treatment. Higher death rates were
      independently associated with weight <35 kg (AOR 3.8; 95%CI 1.9-7.8) and history
      of previous treatment (AOR 3.3; 95%CI 1.5-7.0). CONCLUSIONS: During this first
      year of DOTS implementation with sub-optimal performance, high rates of default
      and death were responsible for low cure rates. Male patients and those with
      alcoholism were at increased risk of default, as were patients identified by
      community survey. To prevent default, directly observed treatment should be made
      more convenient for patients. To reduce mortality, the possible role of
      nutritional interventions should be explored among underweight patients.

PMID- 12234134
TI  - Factors associated with patient and health system delays in the diagnosis of
      tuberculosis in South India.
AB  - OBJECTIVES: To investigate the factors associated with delay in 1) care-seeking
      (patient delay), and 2) diagnosis by health providers (health system delay),
      among smear-positive tuberculosis patients, before large-scale DOTS
      implementation in South India. METHODS: New smear-positive patients were
      interviewed using a structured questionnaire. RESULTS: Among 531 participants,
      the median patient, health system and total delays were 20, 23 and 60 days,
      respectively. Twenty-nine per cent of patients delayed seeking care for > 1
      month, of whom 40% attributed the delay to their lack of awareness about TB. Men
      postponed seeking care for longer periods than women (P = 0.07). In multivariate
      analysis, the patient delay was greater if the patient had initially consulted a
      government provider (adjusted odds ratio [AOR] 2.2, P < or = 0.001), resided at a
      distance >2 km from a health facility (AOR 1.6, P = 0.04), and was an alcoholic
      (AOR 1.6, P = 0.04). Health system delay was >7 days among 69% of patients.
      Factors associated with health system delay were: first consultation with a
      private provider (AOR 4.0, P < 0.001), a shorter duration of cough (AOR 2.6, P =
      0.001), alcoholism (P = 0.04) and patient's residence >2 km from a health
      facility (AOR 1.8, P = 0.02). The total delay resulted largely from a long
      patient delay when government providers were consulted first, and a long health
      system delay when private providers were consulted first. CONCLUSION: Public
      awareness about chest symptoms and the availability of free diagnostic services
      should be increased. Government and private physicians should be educated to be
      aware about the possibility of tuberculosis when examining out-patients.
      Effective referrals for smear microscopy should be developed between private and
      public providers.

PMID- 12234135
TI  - Why do patients with a cough delay seeking care at Lusaka urban health centres? A
      health systems research approach.
AB  - SETTING: Primary health centres in urban Lusaka, Zambia. OBJECTIVES: To describe
      the distribution and risk factors for delay among patients presenting with a
      cough to the urban health centres. DESIGN: A health systems research methodology
      was used. A participatory workshop analysed the problem and designed a cross
      sectional survey of patients attending two urban health centres. Initial data
      analyses were performed in a second workshop, with results discussed with a broad
      range of policy-makers, health care staff and community members interested in
      tuberculosis. RESULTS: A total of 427 patients were interviewed; 35% had delayed
      for more than one month. Delay was associated with older age, severe underlying
      illness, poor perception of the health services, distance from the clinic and
      prior attendance at a private clinic. There was no relationship between delay and
      knowledge about tuberculosis, nor with education, socio-economic level or gender.
      Tuberculosis and HIV were felt to be closely linked and highly stigmatised, but
      stigmatising attitudes were not associated with longer delays. CONCLUSIONS: The
      health systems research methodology was an effective way to engage the staff of
      the district health services in action-oriented research. Investing in
      improvements in the health system and ensuring accessibility for older and more
      disabled patients is likely to reduce delays in diagnosis and help to improve
      tuberculosis control in Lusaka.

PMID- 12234136
TI  - Tuberculosis in children dying with HIV-related lung disease: clinical
      pathological correlations.
AB  - SETTING: Chris Hani Baragwanath Hospital, Soweto, South Africa. OBJECTIVES: To
      compare post mortem histological, microbiological and biochemical findings with
      clinical and radiological data generated ante mortem in children infected with
      HIV dying from clinical lung disease. METHODS: Post mortem lung and liver
      biopsies were undertaken on 93 consecutive deaths in children with HIV. Specimens
      were processed for culture, histology and staining for M. tuberculosis,
      Pneumocystis carinii pneumonia (PCP) and cytomegalovirus (CMV). Post mortem
      diagnoses were compared with clinical and radiological data generated during the
      final hospitalisation. RESULTS: Tuberculosis (TB) was diagnosed post mortem in
      four (4.3%) cases; a further 17 (18.2%) patients had been treated empirically for
      TB before death, and the remaining 72 (77.5%) patients had not been treated for
      TB. TB was more prevalent in children aged 1 year or older (13.4%) than in
      younger patients (1.4%) (P < 0.025). Patients with PCP, CMV pneumonitis or
      lymphocytic interstitial pneumonitis (LIP) had the same clinical presentation or
      radiographic appearances as patients with TB. The only features distinguishing
      patients with TB were older age and ante mortem gastric aspirate cultures
      positive for M. tuberculosis. CONCLUSION: The diagnosis of TB in children
      infected with HIV remains difficult. Clinical and radiographic features are
      shared with other opportunistic diseases. Case identification strategies relying
      on clinical and radiographic findings lead to overtreatment, particularly in
      children younger than 1 year of age. Gastric aspirate cultures remain a reliable
      tool for the identification of infected patients.

PMID- 12234137
TI  - Observer variation in detecting lymphadenopathy on chest radiography.
AB  - OBJECTIVE: To assess inter- and intra-observer agreement in the detection of
      lymphadenopathy on chest radiography in children at risk for tuberculosis.
      PATIENTS AND METHODS: Retrospective examination of the antero-posterior and
      lateral chest radiographs of children aged 1 month to 11 years discharged from
      the short-stay ward of the Red Cross Children's Hospital, Cape Town, with a
      diagnosis of tuberculosis or pneumonia. Four paediatric pulmonologists viewed the
      radiographs independently. The main outcome measures were inter- and intra
      observer agreement on the presence or absence of lymphadenopathy, reported as
      present, absent or equivocal, and expressed as weighted kappa statistics.
      RESULTS: Weighted kappa for the six pairs of observers ranged from 0.14 (95%CI
      0.02-0.30) to 0.52 (95%CI 0.35-0.69). After a 3-month interval, intra-observer
      agreement ranged from 0.44 (95%CI 0.25-0.62) to 0.71 (95%CI 0.56-0.87). The
      average weighted kappa for inter-observer agreement was 0.33, and the average
      intra-observer kappa was 0.55. CONCLUSIONS: There was 'fair' inter- and
      'moderate' intra-observer agreement among paediatric pulmonologists in detecting
      lymphadenopathy on chest radiography in children. Caution is necessary when
      basing clinical decisions on the presence of lymphadenopathy on chest
      radiography.

PMID- 12234139
TI  - Ten-year trends in smoking behaviour among adults in southern Germany.
AB  - SETTING: The city of Augsburg and two adjacent counties, covering a population of
      532,987. OBJECTIVE: To provide a detailed description of trends in smoking
      behaviour among adults according to age, gender and educational status in
      southern Germany. DESIGN: Cross sectional surveys performed 10 years apart (1985
      and 1995) in the Augsburg region as part of the WHO MONICA project. PARTICIPANTS:
      Of a total of 9261 eligible subjects, 7938 adults aged 25-64 years (4022 in 1985
      and 3916 in 1995) from two separate random samples responded to the survey,
      giving a response rate of 79% in 1985 and 75% in 1995. RESULTS: In both surveys,
      daily smoking among men showed a clear pattern of reverse association with age
      and educational status, while women showed only an age-smoking pattern. Between
      1985 and 1995, daily smoking showed a general increase among women and a decrease
      among men, with most of the increase in smoking prevalence as well as in numbers
      of cigarettes consumed by smokers occurring in women with a low level of
      education. Smoking cessation generally showed a positive relation to education in
      each survey for both sexes, and an increasing trend among all educational groups
      in the 10-year period between 1985 and 1995. CONCLUSION: The 10-year trends in
      smoking behaviour in southern Germany show features of early stage III of the
      smoking epidemic, where smoking is decreasing among men and continuing to rise
      among women, but with signs of levelling off in some social strata. Particular
      attention should be paid to combating smoking trends among women with low levels
      of education.

PMID- 12234138
TI  - 5' dinucleotide repeat polymorphism of NRAMP1 and susceptibility to tuberculosis
      among Caucasian patients in Houston, Texas.
AB  - SETTING: Houston Tuberculosis Initiative (HTI) and Baylor College of Medicine,
      Houston, Texas. OBJECTIVE: To further explore the association between the
      polymorphisms of NRAMP1 and human susceptibility/resistance to tuberculosis (TB),
      specifically to determine whether the reported association shown for blacks and
      Asians holds true for Caucasian populations. DESIGN: In a case-control study, 135
      adult Caucasian TB patients and 108 adult Caucasian HIV-seronegative non-TB
      controls were analyzed for the association between the polymorphisms in NRAMP1
      gene and clinical TB. RESULTS: Heterozygote at 5'(GT)n, a dinucleotide repeat
      polymorphism in the promoter of NRAMP1, was observed at significantly higher
      frequencies among HIV-negative patients with pulmonary TB (41.6%; OR 2.02; 95%CI
      1.11-3.64), extra-pulmonary TB (66.7%; OR 4.80; 95%CI 1.34-17.15), and HIV
      seropositive TB patients (50%; OR 3.77; 95%CI 1.33-10.66) in comparison with the
      controls (27.8%). Homozygotes (GT)(10,10) were over-represented among HIV
      positive TB patients (18.2%; OR 6.86; 95%CI 1.55-30.21) compared to the controls
      (5.5%). CONCLUSION: These findings suggest that the 5'(GT)n polymorphism of
      NRAMP1 modifies TB susceptibility in this Caucasian population, and could
      possibly be related to the site of infection among HIV-negative individuals and
      HIV-coinfected TB.

PMID- 12234140
TI  - An outbreak of Legionnaires' disease in an inner city district: importance of the
      first 24 hours in the investigation.
AB  - OBJECTIVE: To present the main results of the investigation of an outbreak of
      Legionnaire's disease that occurred in an inner city district of Barcelona
      between 15 October and 15 November 2000. METHODS: Epidemiological surveys of
      patients and environmental investigations were initiated on the day the first
      five cases were notified. Water samples and smears from cooling tower trays were
      taken for microbiological analysis. Maps of the distribution of cases and
      possible contamination foci were elaborated. Incidences were calculated for each
      census tract. RESULTS: A total of 54 patients related to the outbreak were
      identified, with a case fatality rate of 5.5%. Incidence rate in the area closest
      to the cooling tower (6.40/1000) was significantly higher than that of the rest
      of the neighbourhood (2.23/1.000, RR 2.87, 95%CI 1.37-6.12, P = 0.0035). Cultures
      positive for Legionella pneumophila serogroup 1, subtypes Pontiac, Philadelphia
      or Allentown, were obtained from eight patients. On the 39th day of the
      investigation it was found that the strain isolated in one of the cooling towers
      coincided with the serogroup, subtype and molecular profiles identified in
      clinical samples. CONCLUSIONS: Rapid coordination of clinicians, microbiologists,
      epidemiologists and environmentalists permitted the source of infection and the
      affected cases to be correlated within a few days.

PMID- 12234141
TI  - Lack of toxicity from concomitant directly observed disulfiram and isoniazid
      containing therapy for active tuberculosis.
AB  - We retrospectively evaluated the use of disulfiram among alcoholic patients being
      treated for active tuberculosis. There were 13 alcoholics treated with
      disulfiram, 105 alcoholics not on disulfiram, and 249 non-alcoholics. Rates of
      toxicity were higher among alcoholics than among non-alcoholics (58% vs. 32%),
      but there was no difference between alcoholics taking and those not taking
      disulfiram (61% vs. 57%). There were no neurological side effects in the
      disulfiram group. Disulfiram appeared to be safe when added to intermittent,
      directly observed isoniazid-containing tuberculosis treatment, and was useful in
      managing complications of alcohol abuse. However, the small number of patients on
      disulfiram limits the strength of this negative finding.

PMID- 12234143
TI  - Nitrate uptake, nitrate reductase distribution and their relation to proton
      release in five nodulated grain legumes.
AB  - Nitrate uptake, nitrate reductase activity (NRA) and net proton release were
      compared in five grain legumes grown at 0.2 and 2 mM nitrate in nutrient
      solution. Nitrate treatments, imposed on 22-d-old, fully nodulated plants, lasted
      for 21 d. Increasing nitrate supply did not significantly influence the growth of
      any of the species during the treatment, but yellow lupin (Lupinus luteus) had a
      higher growth rate than the other species examined. At 0.2 mM nitrate supply,
      nitrate uptake rates ranged from 0.6 to 1.5 mg N g(-1) d(-1) in the order: yellow
      lupin > field pea (Pisum sativum) > chickpea (Cicer arietinum) > narrow-leafed
      lupin (L angustifolius) > white lupin (L albus). At 2 mM nitrate supply, nitrate
      uptake ranged from 1.7 to 8.2 mg N g(-1) d(-1) in the order: field pea > chickpea
      > white lupin > yellow lupin > narrow-leafed lupin. Nitrate reductase activity
      increased with increased nitrate supply, with the majority of NRA being present
      in shoots. Field pea and chickpea had much higher shoot NRA than the three lupin
      species. When 0.2 mM nitrate was supplied, narrow-leafed lupinreleased the most
      H+ per unit root biomass per day, followed by yellow lupin, white lupin, field
      pea and chickpea. At 2 mM nitrate, narrow-leafed lupin and yellow lupin showed
      net proton release, whereas the other species, especially field pea, showed net
      OH- release. Irrespective of legume species and nitrate supply, proton release
      was negatively correlated with nitrate uptake and NRA in shoots, but not with NRA
      in roots.

PMID- 12234144
TI  - Measuring and simulating crown respiration of Scots pine with increased
      temperature and carbon dioxide enrichment.
AB  - Acclimation to elevated atmospheric carbon dioxide concentration and temperature
      of respiration by the foliage in the crown of Scots pine (Pinus sylvestris) trees
      is measured and modelled. Starting in 1996, individual 20-year-old trees were
      enclosed in chambers and exposed to either normal ambient conditions (CON),
      elevated CO2 concentration (EC), elevated temperature (ET) or a combination of EC
      and ET (ECT). Respiration of individual leaves within the crown was measured in
      2000. To extrapolate the response of respiration of individual leaves to the
      whole crown, a multi-layer model was developed and used to predict daily and
      annual crown respiration, in which the crown structure and corresponding
      microclimate data were used as input. Respiration measurements showed that EC led
      to higher Q10 values (4.6%) relative to CON, but lower basal respiration rates at
      20 degrees C [R1.d(20)] (-7.1%) during the main growth season (days 120-240),
      whereas ET and ECT both reduced Q10 (-12.0 and -9.8%, respectively) throughout
      the year but increased R1.d(20) (27.2 and 21.6%, respectively) during the period
      of no-growth, and slightly reduced R1.d(20) (-1.7 and -2.8%, respectively) during
      the main growth season. Model computations showed that annual crown respiration
      increased: (1) by 16% in EC, with 92% of this increase attributable to the
      increase in foliage area; (2) by 35% in ET, with 66% related to the increase in
      foliage area and 17% to the rise in ambient temperature; and (3) by 27% in the
      case of ECT, with 43% attributable to the increase in foliage area and 29% to the
      rise in ambient temperature. Changed respiration parameters for individual
      leaves, induced by treatments, made only a small contribution to the annual crown
      respiration compared with the increased foliage area. The effects of changes in
      crown architecture and nitrogen distribution, caused by treatments, on the daily
      and annual course of crown respiration are discussed.

PMID- 12234142
TI  - The role of aquaporins in root water uptake.
AB  - The capacity of roots to take up water is determined in part by the resistance of
      living tissues to radial water flow. Both the apoplastic and cell-to-cell paths
      mediate water transport in these tissues but the contribution of cell membranes
      to the latter path has long been difficult to estimate. Aquaporins are water
      channel proteins that are expressed in various membrane compartments of plant
      cells, including the plasma and vacuolar membranes. Plant aquaporins are encoded
      by a large multigene family, with 35 members in Arabidopsis thaliana, and many of
      these aquaporins show a cell-specific expression pattern in the root. Mercury
      acts as an efficient blocker of most aquaporins and has been used to demonstrate
      the significant contribution of water channels to overall root water transport.
      Aquaporin-rich membranes may be needed to facilitate intense water flow across
      root tissues and may represent critical points where an efficient and spatially
      restricted control of water uptake can be exerted. Roots, in particular, show a
      remarkable capacity to alter their water permeability over the short term (i.e.
      in a few hours to less than 2-3 d) in response to many stimuli, such as day/night
      cycles, nutrient deficiency or stress. Recent data suggest that these rapid
      changes can be mostly accounted for by changes in cell membrane permeability and
      are mediated by aquaporins. Although the processes that allow perception of
      environmental changes by root cells and subsequent aquaporin regulation are
      nearly unknown, the study of root aquaporins provides an interesting model to
      understand the regulation of water transport in plants and sheds light on the
      basic mechanisms of water uptake by roots.

PMID- 12234145
TI  - Soil cations influence bryophyte susceptibility to bisulfite.
AB  - The hypothesis that metal ions absorbed by bryophytes from the underlying soil
      may ameliorate adverse effects of SO2 was investigated in the terricolous moss
      species Pleurozium schreberi (Brid.) Mitt. and Rhytidiadelphus triquetrus (Hedw.)
      Warnst. Dilute sodium bisulfite solutions (equivalent to dissolved SO2) were
      applied to shoots isolated from soil or in contact with artificial substrata.
      Marked inhibition of net photosynthesis was observed within 2 h of treatment with
      0.3 mM bisulfite in both mosses. Progressive recovery of net photosynthesis
      occurred 2-8 h after bisulfite treatment, although the extent of this depended on
      the concentration and pH of the solution. When R. triquetrus and P. schreberi
      were grown on artificial substrata (calcareous, acid-mineral or acid-organic)
      with weekly bisulfite applications, the only significant effect was poorer growth
      of P. schreberi receiving bisulfite on the calcareous and acid-organic substrata.
      In both species, growth on the calcareous substratum led to increased
      concentrations of exchangeable Ca2+, whereas exchangeable Fe3+ concentrations
      increased following growth on the acid-mineral soil. In another experiment the
      two mosses were pre-treated with either Ca2+ or Fe3+ before incubation with
      bisulfite. In P. schreberi, the depression of net photosynthetic rate caused by
      bisulfite was ameliorated from 33 to 64% of the control by pre-treatment with
      Fe3+, but it was unaffected by Ca2+ pre-treatment. In R. triquetrus, the
      amelioration caused by Fe3+ pre-treatment was from 16 to 60% of the control, but
      pre-treatment with Ca2+ gave a greater amelioration, to 75% of the control value.
      The responses are discussed in terms of soil preferences of the mosses and
      possible underlying bisulfite amelioration mechanisms.

PMID- 12234146
TI  - Intra- and interspecific variation in DNA content in Cistus (Cistaceae).
AB  - Flow cytometry, using propidium iodide and 4',6-diamidano-2-phenylindole
      staining, was used to estimate the nuclear DNA content (2C) and the proportion of
      A-T base pairs in 16 species of the Mediterranean genus Cistus. Genome sizes were
      shown to be constant within species, since no significant intraspecific variation
      in 2C DNA content was detected. At the genus level, up to about 1.5-fold
      differences in absolute DNA amounts were observed, ranging from 3.92 pg in C.
      crispus to 5.88 pg in C. monspeliensis. The (AT) : (GC) ratio was close to 1, and
      was similar for all species examined, ranging from 47.87% A-T content in C
      clusii, to 50.67% in C. populifolius. Pink-flowered species (subgenus Cistus) had
      lower DNA amounts than white-flowered species (subgenera Leucocistus and
      Halimioides). However, the distribution of DNA amounts in Cistus appeared to be
      continuous and did not permit a clear separation of infra-generic ranks in the
      genus.

PMID- 12234147
TI  - Modelling of temperature-controlled internode elongation applied to
      chrysanthemum.
AB  - The DIF concept states that equal internode length can be achieved with the same
      difference between day and night temperature irrespective of the mean 24 h
      temperature. However, the physiological background of the DIF concept is unclear.
      An attempt to model internode elongation is presented based on three plausible
      processes, namely (1) the accumulation of elongation requirements during the day,
      (2) elongation during the night using elongation requirements and (3) the
      limitation of internode length due to low turgor pressure unable to counter cell
      wall elasticity. Each reaction rate constant, one per process, depends on
      temperature according to Arrhenius' Law. The resulting process-based model
      describes internode elongation in time and was calibrated on a chrysanthemum data
      set. Chrysanthemum plants were grown in growth chambers with rigorously defined
      day and night temperatures. In total, 16 temperature treatments were applied,
      resulting from the combination of four day and four night temperatures (16, 20,
      24 and 28 degrees C). Internode elongation was measured for the tenth internode
      in ten plants per treatment. The percentage variance accounted for, R2adj, was
      almost 91%. Transferability of model parameters was shown to exist by cross
      validation. Simulation of the internode length in time as function of mean 24 h
      temperature and DIF showed that the DIF concept is not apparent after a growing
      period of 10 d, but is visible after 20 d. This model structure for describing
      internode elongation might also be applicable for other plants that show the DIF
      concept.

PMID- 12234148
TI  - Flower and spikelet morphology in sawgrass, Cladium jamaicense Crantz
      (Cyperaceae).
AB  - In recent systematic treatments of the Cyperaceae, spikelets of all but the most
      primitive tribes have been considered to be indeterminate, whereas historically
      the number of flowers, floral sex and distribution of sexes in spikelets have
      been important characters in suprageneric classifications. However, descriptions
      of these spikelet characteristics for sawgrass, Cladium jamaicense Crantz, vary
      among authors. Spikelet morphology was analysed using developmental and
      phenological studies of sawgrass populations in south Florida, USA. Sawgrass
      spikelets have two flowers that expand successively. Flowers are fundamentally
      hermaphroditic and protogynous. The first flower to expand (F1) terminates the
      spikelet axis, whereas the second flower (F2), ensheathed by an addorsed
      prophyll, develops in the axil of the last bract produced on the axis. In 86% of
      the spikelets examined from ramets of three populations, the gynoecium of the F1
      flower aborted, so this flower was functionally male and the spikelet was
      protandrous. However, in 14% of spikelets from these individuals, the F1 flower
      was hermaphroditic and could set seed. The F2 flower was typically hermaphroditic
      and matured stigmas, then anthers. Thus, spikelets in C. jamaicense are
      determinate and have two flowers that are dichogamous both within flowers and
      between flowers in a spikelet; spikelet sex expression can vary among plants and
      populations, especially in the first flower. These data for sawgrass suggest that
      a re-examination of spikelet development and phenology in other genera is needed
      to clarify the expression of these characters in the family.

PMID- 12234149
TI  - Correlation of cytokinin levels in the endosperms and roots with cell number and
      cell division activity during endosperm development in rice.
AB  - Cell number and cell division activity in rice (Oryza sativa) endosperms are
      possibly regulated by cytokinin levels in the endosperm and its source in the
      roots. This study tried to find the possible correlations among them. Six rice
      genotypes were grown in nutrient solution. Two patterns of endosperm cell
      division, synchronous and asynchronous, were observed among the genotypes based
      on the cell division rate of superior and inferior spikelets. Contents of zeatin
      (Z) + zeatin riboside (ZR) were much higher than those of N6-isopentenyladenine
      (iP) and N6-isopentenyladenosine (iPR) in both endosperms and roots. Changes in Z
      + ZR levels in endosperms were significantly correlated with those in roots, and
      both were very significantly correlated with the cell division rate. Changes in
      iP + iPR contents in the roots were not significantly correlated with those in
      the endosperms and the cell division rate. When roots were treated with kinetin,
      endosperm cell number and grain weight were increased. Such enhancement was more
      significantly achieved by the root kinetin treatment than by spraying kinetin on
      leaves and panicles. The results suggest that the cell number and cell division
      activity in rice endosperms are regulated by cytokinin levels in the endosperm
      and that root-derived Z + ZR play a pivotal role.

PMID- 12234150
TI  - A developmentally based categorization of branching in Trifolium repens L.:
      influence of nodal roots.
AB  - This study describes the successive stages of development of branches from
      axillary buds in fully rooted plants of Trifolium repens grown in near optimal
      conditions, and the way in which this developmental pathway differs when nodal
      root formation is prevented as plants grow out from a rooted base. Cuttings of a
      single genotype were established in a glasshouse with nodal root systems on the
      two basal phytomers and grown on so that nodal rooting was either permitted (+R)
      or prevented (-R). In +R plants, axillary tissues could be assigned to one of
      four developmental categories: unemerged buds, emerged buds, unbranched lateral
      branches or secondarily branched lateral branches. In -R plants, branch
      development was retarded, with the retardation becoming increasingly pronounced
      as the number of -R phytomers on the primary stolon increased. Retarded
      elongation of the internodes of lateral shoots on -R plants resulted in the
      formation of a distinct fifth developmental category: short shoots (defined as
      branches with two or more leaves but with mean internode length equal to, or less
      than, 10% of that of the immediately proximal internode on the parent stolon)
      which had reduced phytomer appearance rates but retained the potential to develop
      into lateral branches. Transfer of +R plants to -R conditions, and vice versa,
      after 66 d demonstrated that subsequent branch development was wholly under the
      control of the youngest nodal root present, regardless of the age and number of
      root systems proximal to it.

PMID- 12234151
TI  - Natural and induced polyploidy in Acacia dealbata Link. and Acacia mangium Willd.
AB  - Seeds were obtained from seven natural populations of Acacia dealbata, three
      natural populations of A. mangium and a seed orchard of A. mangium, representing
      the natural range of the two species. Polyploids were discovered in two of the
      seven populations of A. dealbata. The 2C DNA amount for diploid A. dealbata (2n =
      2x = 26) was 1.74 pg, and for diploid A. mangium (2n = 2x = 26) was 1.30 pg. A
      naturally occurring tetraploid of A. dealbata (2n = 4x = 52) had a 2C DNA amount
      of 3.41 pg and a naturally occurring triploid genotype had a 2C DNA amount of
      2.53 pg. The use of colchicine and oryzalin was investigated as a means of
      producing higher frequencies of tetraploids of both A. mangium and A. dealbata
      for incorporation into breeding programmes. Colchicine treatment gave tetraploid
      frequencies up to 29% for A. dealbata seedlings, and up to 18% for A. mangium
      seedlings. In contrast, no tetraploid A. mangium was detected following oryzalin
      treatment, and the low frequencies of tetraploids observed in A. dealbata could
      be attributed to their natural occurrence.

PMID- 12234152
TI  - Carbon dioxide concentration at night affects translocation from soybean leaves.
AB  - Studies have indicated that the concentration of carbon dioxide [CO2] during the
      dark period may influence plant dry matter accumulation. It is often suggested
      that these effects on growth result from effects of [CO2] on rates of
      respiration, but responses of respiration to [CO2] remain controversial, and
      connections between changes in respiration rate and altered growth rate have not
      always been clear. The present experiments tested whether translocation, a major
      consumer of energy from respiration in exporting leaves, was sensitive to [CO2].
      Nineteen-day-old soybean plants grown initially at a constant [CO2] of 350
      micromol mol(-1) were exposed to three consecutive nights with a [CO2] of 220
      1400 micromol mol(-1), with a daytime [CO2] of 350 micromol mol(-1). Change in
      dry mass of the individual second, third and fourth trifoliate leaves over the 3
      d period was determined, along with rates of respiration and photosynthesis of
      second leaves, measured by net CO2 exchange. Translocation was determined from
      mass balance for second leaves. Additional experiments were conducted where the
      [CO2] around individual leaves was controlled separately from that of the rest of
      the plant. Results indicated that low [CO2] at night increased both respiration
      and translocation and elevated [CO2] decreased both processes, to similar
      relative extents. The effect of [CO2] during the dark on the change in leaf mass
      over 3 d was largest in second leaves, where the change in mass was about 50%
      greater at 1400 micromol mol(-1) CO2 than at 220 micromol mol(-1) CO2. The
      response of translocation to [CO2] was localized in individual leaves. Results
      indicated that effects of [CO2] on net carbon dioxide exchange rate in the dark
      either caused or reflected a change in a physiologically important process which
      is known to depend on energy supplied by respiration. Thus, it is unlikely that
      the observed effects of [CO2] on respiration were artefacts of the measurement
      process in this case.

PMID- 12234153
TI  - A stochastic flowering model describing an asynchronically flowering set of
      trees.
AB  - A general stochastic model is presented that simulates the time course of
      flowering of individual trees and populations, integrating the synchronization of
      flowering both between and within trees. Making some hypotheses, a simplified
      expression of the model, called the 'shoot' model, is proposed, in which the
      synchronization of flowering both between and within trees is characterized by
      specific parameters. Two derived models, the 'tree' model and the 'population'
      model, are presented. They neglect the asynchrony of flowering, respectively,
      within trees, and between and within trees. Models were fitted and tested using
      data on flowering of Psidium cattleianum observed at study sites at elevations of
      200, 520 and 890 m in Reunion Island. The 'shoot' model fitted the data best and
      reproduced the strong irregularities in flowering shown by empirical data. The
      asynchrony of flowering in P. cattleianum was more pronounced within than between
      trees. Simulations showed that various flowering patterns can be reproduced by
      the 'shoot' model. The use of different levels of organization of the general
      model is discussed.

PMID- 12234154
TI  - A preliminary investigation of the role of auxin and cytokinin in sylleptic
      branching of three hybrid poplar clones exhibiting contrasting degrees of
      sylleptic branching.
AB  - Sylleptic branches grow out from lateral buds during the same growing season in
      which the buds are formed. This type of branching is present in poplar and in
      many tropical species. It results in the production of more branches, more leaves
      and expanded photosynthetic capacity and is thought to assist in increasing the
      overall growth and biomass of the tree at a young age. However, very little is
      known about the physiology of sylleptic branching in poplar, which is an
      extremely important source of fibre and fuel. In the present study of three
      hybrid poplar clones (11-11, 47-174 and 49-177) of Populus trichocarpa x P.
      deltoides exhibiting contrasting degrees of sylleptic branching, an analysis was
      carried out on parent shoot elongation and sylleptic branching, together with a
      preliminary comparison of the parent shoots' sensitivity to auxin
      (naphthaleneacetic acid) as a repressor of lateral bud outgrowth, and cytokinin
      (benzyladenine) as a promoter. Suggestive evidence was found for an inverse
      correlation between parent shoot sensitivity to auxin and the degree of sylleptic
      branching, as well as a partially positive correlation with respect to
      sensitivity to cytokinin. The present data are consistent with the hypothesis
      that auxin and cytokinin may play repressive and promotive roles, respectively,
      in the sylleptic branching of hybrid poplar.

PMID- 12234155
TI  - Acne vulgaris, I: pathogenesis and diagnosis.
AB  - Acne vulgaris is a chronic inflammatory disease of the pilosebaceous units. It is
      a pleomorphic disorder with multifactorial pathogenesis. The many expressions of
      acne rarely present a diagnostic challenge, but correct classification of acne is
      crucial in choosing the appropriate therapies. Although previous research has
      provided a better understanding of the pathogenic factors, there is still a great
      deal to be learned.

PMID- 12234156
TI  - Using oral tetracycline and topical betamethasone valerate to treat
      acrodermatitis continua of hallopeau.
AB  - Acrodermatitis continua of Hallopeau (ACH) is a rare type of localized pustular
      psoriasis. We report the case of a 65-year-old alcoholic woman who had severe
      inflammatory ACH for 10 years. Initial therapy with sulfasalazine was
      unsuccessful. The patient was then treated with oral tetracycline and topical
      betamethasone valerate with occlusive dressing. Her condition improved
      dramatically after one week.

PMID- 12234157
TI  - Acne vulgaris, II: treatment.
AB  - Treatment of acne vulgaris is based on a current understanding of the pathogenic
      factors. Effective management can be achieved for each individual patient using a
      variety of the powerful weapons in our therapeutic arsenal.

PMID- 12234158
TI  - Isotretinoin made S.M.A.R.T. and simple.
AB  - With the introduction of oral isotretinoin 20 years ago, an incredible triumph
      was achieved in the treatment of acne vulgaris. Much has been learned of the
      pathogenesis of acne and the mechanism by which isotretinoin affects acne. The
      teratogenicity of isotretinoin has cast a shadow on this effective drug with
      recent concern about the regulation of its use. The S.M.A.R.T. program has been
      implemented to address this concern. Alleged depressive mood effects of
      isotretinoin have resulted in further controversy. The efficacy of and
      indications for isotretinoin use are discussed here, with elaboration on the
      reported side effects. Given its established risks, treatment with isotretinoin
      may become severely curtailed if caution is not exercised.

PMID- 12234159
TI  - Fixed drug eruption to rofecoxib.
AB  - Rofecoxib, used for dysmenorrhea, caused a herpetiform fixed drug eruption
      predominantly involving the lips with classic clinical and histological findings
      in a red-brown lesion on the dorsal hand.

PMID- 12234160
TI  - Retinoic acid receptors and topical acne therapy: establishing the link between
      gene expression and drug efficacy.

PMID- 12234162
TI  - Acne 2002.

PMID- 12234161
TI  - The interaction between acne vulgaris and the psyche.
AB  - Acne is the most common problem that presents to dermatologists. Because it
      causes visible disfiguring of the face, it produces a great deal of
      embarrassment, frustration, anger, and depression in patients. In addition, acne
      is most common in adolescence and young adulthood, a time when patients are least
      capable of coping with additional stress. As a result, it is virtually impossible
      to separate acne from psychiatric disturbances. Some patients are severely
      affected and require more than just acne therapy. Dermatologists need to become
      more adept at diagnosing and treating causative, concomitant, and resultant
      psychiatric disturbances in patients with acne. This article is intended to
      highlight the scope of the problem, identify at-risk patients, and help
      dermatologists assist patients with both their acne and their psychologic
      response to it.

PMID- 12234163
TI  - Photo quiz. Trichrome tinea versicolor.

PMID- 12234164
TI  - Powerlifter's purpura: a valsalva-associated phenomenon.
AB  - The causes of purpura can be classified into intravascular, vascular, and
      extravascular mechanisms. We describe a case of cervicofacial purpura in a
      powerlifter attributed to the accompanying Valsalva-associated increased arterial
      pressure. Powerlifting should be added to the list of activities that may cause
      purpura.

PMID- 12234165
TI  - Conference synopsis: hematopoietic stem cell therapy in autoimmune diseases,
      October 2001.
AB  - Since 1996, patients with autoimmune diseases have been treated on single-arm
      investigational protocols with high-dose immunosuppressive therapy and autologous
      peripheral blood stem cell transplantation (HSCT). In a conference held in
      October 2001 at the City of Hope National Medical Center, participants discussed
      current laboratory studies in autoimmunity, the rationale of HSCT in autoimmune
      diseases, results of phase I-II studies, and the prospects for controlled trials.
      This conference synopsis summarizes major discussion points in clinical sessions
      and in sessions devoted to ethical and regulatory aspects of this investigational
      treatment. Protocols for controlled studies in multiple sclerosis (MS) and
      systemic sclerosis (SSc), originating in Europe and in the United States, have
      been designed or are in the final stages of design. The only controlled trial
      presently underway is for SSc in Europe (Autologous Stem Cell Transplantation
      International Scleroderma Trial [ASTIS]). There are current plans for a
      controlled trial for rheumatoid arthritis (RA) in Europe (ASTIRA) but not in the
      United States. Eventual cross-study analysis of the European and United States
      trials may give valuable comparative information on the different mobilization
      and immunosuppressive regimens used. Recognition of the importance of axonal
      degeneration in secondary progressive MS and the use of mitoxantrone as a rescue
      medication are two relatively recent developments now being considered in the
      design of controlled HSCT protocols in MS. The importance of informed consent and
      study accessibility was discussed as well as the continuing role of the US Food
      and Drug Administration in regulating these protocols in the United States.

PMID- 12234166
TI  - Efficient induction of minor histocompatibility antigen HA-1-specific cytotoxic T
      cells using dendritic cells retrovirally transduced with HA-1-coding cDNA.
AB  - Cytotoxic T-cells (CTLs) specific for the hematopoietic system-restricted minor
      histocompatibility antigen (mHag) HA-1 efficiently lyse HA-1-positive leukemic
      cells without affecting nonhematopoietic cells. HA-1-specific CTLs are thus
      potential tools for adoptive immunotherapy of relapsed leukemia after HLA-matched
      HA-1-mismatched stem cell transplantation (SCT). In vitro generation of HA-1
      specific CTLs from SC donors is possible using dendritic cells (DCs) pulsed with
      synthetic HA-1 peptide as stimulator cells. However, this approach requires at
      least 6 weeks of in vitro culturing under GMP (good manufacturing practice)
      conditions. Our data show that in vitro induction of HA-1-specific CTLs is more
      rapid with the use of DCs that are retrovirally transduced with the HA-1
      complementary DNA. Retrovirally transduced DCs showed functional and long-term
      stable expression of the HA-1 CTL epitope in primary CTL cultures. In 4 SC
      donors, HA-1-transduced DCs induced HA-1-specific CTLs in 14 to 21 days. The in
      vitro-generated CTL lines contained 6% to 9% T-cells that stained brightly with
      tetrameric HLA-A2/HA-1 peptide complexes (HA-1(A2) tetramer) and showed
      significant lysis of HA-1+ leukemic cells. The CTL induction procedure using
      peptide-pulsed DCs was less effective and required 28 to 35 days of T-cell
      culture. Thus, sustained presentation of mHag HA-1 by retrovirally transduced DCs
      facilitates the in vitro induction of HA-1-specific CTLs.

PMID- 12234167
TI  - Phase II study of a moderate-intensity preparative regimen with allogeneic
      peripheral blood stem cell transplantation for hematologic diseases: the Texas
      Transplant Consortium experience.
AB  - Conventional preparative regimens for allogeneic stem cell transplantation are
      associated with excessive regimen-related toxicity (RRT) in some patients because
      of underlying comorbidities, advanced age, or prior treatment. We studied a
      preparative regimen designed to reduce RRT, yet allow for adequate engraftment
      and development of a graft-versus-malignancy effect. Thirty patients (median age,
      57 years) were entered on study. Twenty-nine patientsreceived stem cells from HLA
      identical siblings and 1 from a sibling mismatched for 1 antigen at the A locus.
      Sixteen patients had received previous stem cell transplants (6 allogeneic and 10
      autologous). The preparative regimen consisted of fludarabine 30 mg/M2 per day IV
      on day -10 to day -5, busulfan 1 mg/kg per dose PO (n = 6) or 0.8 mg/kg per dose
      IV (n = 24) for 8 doses every 6 hours on day -6 to day -5, and horse-derived
      antithymocyte globulin 5 mg/kg per day IV (n = 12) or 15 mg/kg per day IV (n =
      18) on day -4 to day -1. GVHD prophylaxis consisted of cyclosporine (CYA) 3 mg/kg
      BID PO starting on day -3 (n = 13) or CYA and methotrexate 15 mg/m2 IV on day +1
      and 10 mg/m2 IV on day +3 and day +6 (n = 17). The median number of CD34 cells
      transplanted was 3.19 x 10(6)/kg. All patients demonstrated recovery of
      hematopoietic function. Twenty-six (89%) of 29 evaluable patients achieved
      greater than 90% donor cell chimerism before day 100. Three patients never
      achieved greater than 90% donor chimerism, and another 3 patients subsequently
      lost donor chimerism. All 6 of these patients had autologous reconstitution with
      progressive disease. RRT was minimal; 7 patients had greater than grade II
      nonhematologic toxicity and there were no toxic deaths attributable to the
      conditioning regimen. Transplantation-related mortality was 7% (95% confidence
      interval [CI], 6%-8%) at 3 months and 28% (95% CI, 23%-34%) at 12 months after
      transplantation. Non-relapse-related mortality was most often due to infection.
      Grade II or greater GVHD developed in 56% of evaluable patients, and all patients
      with disease response developed GVHD. Actuarial estimates of overall and disease
      free survival at 12 months were 52% (95% CI, 43%-63%) and 30% (95% CI, 24%-37%),
      respectively. Although this preparative regimen allowed adequate engraftment with
      minimal RRT, GVHD and infectious complications caused significant morbidity and
      mortality. Further study to define appropriate patient populations for this
      regimen, while limiting GVHD and infection risks, is needed.

PMID- 12234168
TI  - Effective purging of autologous hematopoietic stem cells using anti-B-cell
      monoclonal antibody-coated high-density microparticles prior to high-dose therapy
      for patients with non-Hodgkin's lymphoma.
AB  - Contamination of hematopoietic stem cells (HSCs) with tumor cells has been
      associated with increased incidence of relapse in patients with non-Hodgkin's
      lymphoma following autologous HSC transplantation. Effective purging of tumor
      cells may improve the results of HSC transplantation, but current methods of
      purging are technically difficult to perform with large numbers of cells and do
      not consistently remove all detectable cells. We report a pilot clinical trial in
      which 10 patients with relapsed B-cell non-Hodgkin's lymphoma received high-dose
      chemotherapy followed by infusion of autologous HSCs depleted of B-cells by high
      density microparticles (HDM) coated with anti-CD19 and anti-CD20 monoclonal
      antibodies (BCell-HDM). HSCs were mobilized with cyclophosphamide and granulocyte
      colony-stimulating factor. In 6 of the 10 patients, B-cells were detectable by
      immunocytochemical analysis of the apheresis products prior to treatment.
      Following treatment with the BCell-HDM, no B-cells were detected in the products
      from 5 of these patients, a result representing a median depletion of >2.2 logs
      (range, >0.4 to >5.1 logs). The median recovery of nontarget cells postdepletion
      was 73% for CD34 cells and 78% for CD3+ cells. All patients received high-dose
      cyclophosphamide, BCNU (carmustine), and etoposide prior to reinfusion of their B
      cell-depleted autologous HSCs. The median number of CD34+ cells cryopreserved was
      3.6 x 10(6) cells/kg (range, 2.2-10.1 x 10(6) cells/kg). Engraftment was rapid in
      all cases, with a median time to achieve an absolute neutrophil count of 0.5 x
      10(9)/L of 10 days (range, 8-11 days). The median time to achieve a platelet
      count of 20 x 10(9)/L unsupported by platelet transfusion was 11.5 days (range, 8
      17 days). This nonmagnetic negative-depletion technology is simple, rapid, and
      effective in depleting target cells to undetectable levels, with excellent
      recovery of nontarget cells.

PMID- 12234169
TI  - Influence of cytogenetic abnormalities on outcome after allogeneic bone marrow
      transplantation for acute myeloid leukemia in first complete remission.
AB  - Cytogenetic abnormalities detected at diagnosis are recognized as important in
      predicting response to chemotherapy in acute myeloid leukemia (AML). However,
      there is controversy concerning the prognostic significance of karyotype for
      outcome after allogeneic bone marrow transplantation (allo-BMT) performed in
      first complete remission (CR1). This single-institution report describes allo-BMT
      for AML in CR1 and the effect of diagnostic cytogenetic findings on the results
      of that treatment. Between August 1981 and December 1999, 93 patients underwent
      related donor (n = 82) or unrelated donor (n = 11) BMT. Conditioning and GVHD
      prophylaxis were achieved predominantly with busulfan and cyclophosphamide and
      with cyclosporine and methotrexate, respectively. Seventy-nine (85%) of 93
      patients had successful marrow karyotyping at diagnosis, and the patients were
      categorized into 3 prognostic groups based on the British Medical Research
      Council AML 10 trial classification: 15 patients(19%) were classified as having
      favorable risk [inv(16), t(8;2 1), t(15;17)]; 55 (70%) as having intermediate
      risk [no abnormality, +8, +21, +22, del(7q), del(9q), 11q23 rearrangement, and
      other numerical or structural abnormalities]; and 9 (11%) as having adverse risk
      [-5, del(5q), -7, 3q rearrangements, > or = 5 abnormalities, t(6;9), t(9;22)].
      The median follow-up was 93 months (range, 16-241 months). The overall survival
      (OS) rate, event-free survival (EFS) rate, relapse rate, and treatment-related
      mortality (TRM) were not statistically different between the groups. The 5-year
      actuarial EFS rates for favorable, intermediate, and adverse risk groups were 58%
      (95% confidence interval [CI], 29%-79%), 58% (95% CI, 43%-70%), and 67% (95% CI
      28%-88%), respectively. Reclassification of patients into cytogenetic prognostic
      subgroups according to Southwest Oncology Group criteria did not change these
      results. In univariate analysis, the only variable found to have a prognostic
      influence on OS (P = .04) and TRM (P = .03) was the type of donor (unrelated
      donor was linked to a worse prognosis), which was confirmed in multivariate
      analysis. Our study suggests that presentation karyotype has less prognostic
      significance for outcome following allo-BMT than for outcome following
      conventional chemotherapy. In particular, AML patients with poor prognostic
      cytogenetic changes in CR1 who are unlikely to be cured with chemotherapy alone
      may benefit from allo-BMT.

PMID- 12234170
TI  - Development and validation of a scale to measure symptoms of chronic graft-versus
      host disease.
AB  - Chronic GVHD (cGVHD) affects 30% to 90% of surviving allogeneic transplant
      recipients. Thus far, no quality-of-life instruments have been developed to
      measure the effect of this common complication of allogeneic transplantation on
      patients' functioning and well-being. Using a prospective cohort of 107 patients
      with active cGVHD who completed the symptom scale at enrollment and at intervals
      of 3 and 6 months, we developed a 30-item symptom scale with 7 subscales to
      capture the cGVHD-specific symptom burden. The symptom scale correlated highly
      with patients' self-assessed mild, moderate, and severe cGVHD manifestations in
      cross-sectional analysis. Reliability (Cronbach's alpha = 0.79-0.90), test-retest
      (r2 = 0.28-0.93), and convergent and discriminant validity compared to the
      Medical Outcomes Study Short Form 36 (SF-36) and Functional Assessment of Chronic
      Illness Therapy with BMT subscale (FACT-BMT) were assessed and found to be
      adequate. Longitudinal assessments showed that changes in overall health status
      correlated best with changes in quality of life as measured by the SF-36 and FACT
      BMT. In contrast, changes in cGVHD severity were best detected by changes in the
      symptom scale. We recommend that either the SF-36 or the FACT-BMT be combined
      with a cGVHD-specific symptom scale to measure the impact of cGVHD on patients'
      quality of life and that this endpoint be included in clinical trials testing
      cGVHD interventions. The cGVHD symptom scale is a short, simple, and valid
      measure of cGVHD manifestations and can be used to follow complication-specific
      symptoms using patient self-administered questionnaires.

PMID- 12234171
TI  - Correction of phenotype in a thalassemia mouse model using a nonmyeloablative
      marrow transplantation regimen.
AB  - Gene therapy, the replacement of normal human beta- or gamma-globin genes into
      the hematopoietic stem cells of patients with homozygous beta-thalassemia, is a
      promising therapy for the future. High-level lineage-specific stable globin
      expression in transduced cells reinfused into patients in an autologous
      transplantation setting could be curative, if successful. Previous studies have
      shown high-level donor chimerism in nonmyeloablated non-thalassemic hosts. We
      have now studied the conditions for stable long-term engraftment of normal cells
      into a thalassemia mouse model that lead to high-level donor chimerism and
      correction of the abnormal phenotype. Thalassemic female mice treated with 0 to
      300 cGy whole-body irradiation received transplantations of donor cells harvested
      from wild-type males. Engraftment of male cells was quantitated by Y-chromosome
      polymerase chain reaction analysis of blood and marrow progenitors, and changes
      in hemoglobin levels, red cell morphology, and spleen size were measured at
      various times posttransplantation. High-level stable donor cell engraftment was
      achieved in mice given 200 cGy and receiving transplants of 2 x 10(7) or more
      donor cells. The anemia, abnormal peripheral blood smears, and splenomegaly
      improved in the thalassemic mice that had successful engraftment. These studies
      demonstrate that stable and successful levels of engraftment of normal cells can
      correct the thalassemic phenotype without fully myeloablating the host. This
      animal model should allow us to test the amount of cytoreduction required and the
      level of engraftment and beta-globin expression needed in autologous
      transplantation of beta-globin gene-transduced cells to correct the abnormal
      phenotype in thalassemic mice, and it may be relevant to human clinical trials,
      as well.

PMID- 12234172
TI  - Design of photoactive ruthenium complexes to study interprotein electron
      transfer.

PMID- 12234173
TI  - Protection of DNA by alpha/beta-type small, acid-soluble proteins from Bacillus
      subtilis spores against cytosine deamination.
AB  - Spores of Bacillus subtilis contain high levels of proteins, termed alpha/beta
      type small, acid-soluble proteins (SASP), that protect the spore's DNA against
      different types of DNA damage. We tested one such protein, SspC, and two of its
      variants for their ability to protect plasmid DNA against hydrolytic deamination
      of cytosine to uracil. If unrepaired, such damage to DNA causes C to T mutations.
      We found that one SspC variant, SspC(Delta 11-D13K), protected DNA against
      cytosine deamination at two different temperatures (45 and 70 degrees C) and pH
      values (5.2 and 7.9), reducing the rate of deamination by as much as 10-fold. At
      70 degrees C, pH 7.9, the wild-type SspC and its variant, SspC(Delta 11),
      provided little protection against deamination but were effective in protecting
      DNA at 45 degrees C, pH 7.9. Parallel studies of the abilities of these proteins
      to protect DNA against restriction digestion revealed that there was a good
      correlation between the abilities of the proteins to protect against restriction
      endonucleases and reductions in cytosine deaminations. These results show that
      the binding of SspC variants to DNA can prevent attack on DNA bases by water and
      suggest a new general mechanism by which DNA-binding proteins in cells may be
      able to protect chromosomes from endogenous and exogenous reactive chemicals by
      excluding them from the vicinity of DNA.

PMID- 12234174
TI  - Purification and cloning of toxins from elapid venoms that target cyclic
      nucleotide-gated ion channels.
AB  - In 1999, we purified pseudechetoxin (PsTx), the first peptide toxin known to
      block cyclic nucleotide-gated (CNG) ion channels, from the venom of Pseudechis
      australis [Brown, R. L., Haley, T. L., West, K. A., and Crabb, J. W. (1999) Proc.
      Natl. Acad. Sci. U.S.A. 96, 754-759]. Here we report the cloning of the cDNA
      encoding PsTx, as well as the discovery and cloning of pseudecin, a homologous
      toxin from the venom of Pseudechis porphyriacus. The mature proteins are 211 and
      210 amino acids in length, and the amino acid sequences are 96.7% identical,
      differing in only seven residues. The purified toxins were applied to outside-out
      patches excised from Xenopus oocytes expressing CNG channels composed of the rod
      CNGA1 or olfactory CNGA2 channel subunits. Surprisingly, these patch-clamp
      studies revealed a 30-fold difference in affinity between PsTx and pseudecin for
      channels composed of CNGA2 subunits. The apparent K(i) of PsTx was 15 nM, while
      the affinity of pseudecin was 460 nM. The difference in affinities for the CNGA1
      subunit from rod photoreceptors was less pronounced, but the affinity of PsTx was
      70 nM, compared with 1000 nM for pseudecin. This difference in affinity may be
      instructive as we attempt to identify the regions of the toxins that contact CNG
      channels. As the only known protein blockers of CNG channels, these toxins
      promise to be valuable tools to study the structure of the external face of these
      channels.

PMID- 12234175
TI  - Protofibrillar islet amyloid polypeptide permeabilizes synthetic vesicles by a
      pore-like mechanism that may be relevant to type II diabetes.
AB  - Islet amyloid polypeptide (IAPP) and insulin are copackaged and cosecreted by
      pancreatic islet beta-cells. Non-insulin-dependent (type II) diabetes mellitus
      (NIDDM) is characterized by dysfunction and depletion of these beta-cells and
      also, in more than 90% of patients, amyloid plaques containing fibrillar IAPP. An
      aggregated but not necessarily fibrillar form of IAPP is toxic in cell culture,
      suggesting that prefibrillar oligomeric (protofibrillar) IAPP may be pathogenic.
      We report here that IAPP generates oligomeric species in vitro that are consumed
      as beta-sheet-rich fibrils grow. Protofibrillar IAPP, like protofibrillar alpha
      synuclein, which is implicated in Parkinson's disease pathogenesis, permeabilizes
      synthetic vesicles by a pore-like mechanism. The formation of the IAPP amyloid
      pore is temporally correlated to the formation of early IAPP oligomers and its
      disappearance to the appearance of amyloid fibrils. Neither pores nor oligomers
      were formed by the nonfibrillogenic rat IAPP variant. The IAPP amyloid pore may
      be critical to the pathogenic mechanism of NIDDM, as other amyloid pores may be
      to Alzheimer's disease and Parkinson's disease.

PMID- 12234176
TI  - Structure of the third intracellular loop of the human cannabinoid 1 receptor.
AB  - The third cytoplasmic loop (IC3) is a determinant in the dynamic life cycle of G
      protein-coupled receptors, including the activation, internalization,
      desensitization, and resensitization processes. Here, we characterize the
      structural features of the IC3 of the cannabinoid 1 receptor (CB1) in micelle
      solution using heteronuclear, (1)H,(15)N-high-resolution NMR methods. The IC3
      construct was designed to contain one-third of each of the transmembrane helices
      (TMs 5 and 6) to tether the protein to the hydrophobic portion of the micelle.
      Indeed, the NMR analysis illustrates prominent alpha-helices at the N-terminus
      (G1-R10) and C-terminus (Q37-T47) of the IC3 receptor domain, corresponding to
      the cytoplasmic termini of TM5 and TM6. The structural features of the central
      portion of the IC3 consist of a small alpha-helix, adjacent to the terminus of
      TM5. The remainder is mostly unstructured as indicated by the NMR-based
      observables (NOEs and chemical shifts). Despite the lack of secondary structure,
      the hydrophobic triplet of isoleucine residues in the center of the IC3 is found
      in molecular dynamics simulations to associate with the lipid environment,
      producing two smaller loops out of the IC3. Previous studies examining mastoparan
      and related peptides and their ability to activate G proteins have concluded an
      alpha-helix is required for efficient binding and activation. Our structural
      results for the IC3 of CB1 would then suggest that in the intact receptor the G
      protein is activated by the alpha-helices of the cytoplasmic ends of TM5 or TM6
      and not the unstructured central region of the IC3.

PMID- 12234177
TI  - Glycosylation affects the rate of traffic of the Shaker potassium channel through
      the secretory pathway.
AB  - We have examined the effect of glycosylation on the traffic of the voltage-gated
      Shaker potassium channel through the secretory pathway of mammalian cells. Shaker
      is glycosylated on two asparagines (N259 and N263) in the first extracellular
      loop. Electrophysiological experiments indicate that glycosylation is not
      necessary for channel integrity [Santacruz-Toloza et al. (1994) Biochemistry 33,
      5607]. Consistent with this, we observe that unglycosylated N259Q+N263Q mutant
      channel forms oligomers as efficiently as the wild type and that this occurs in
      the endoplasmic reticulum. We have compared the kinetics of secretory traffic of
      the wild-type glycosylated and the N259Q+N263Q unglycosylated channels. Surface
      biotinylation of newly synthesized proteins indicates that the rate of delivery
      of the unglycosylated channel to the cell surface is slower than that of wild
      type. We have further dissected channel traffic using quantitative imaging. We
      observe that mutant channel traffics more slowly from the endoplasmic reticulum
      to the Golgi than wild type at 20 degrees C. This may contribute to the slowed
      delivery of the mutant to the cell surface. Neither the surface fraction at
      steady state nor the stability of Shaker is significantly affected by
      glycosylation in COS cells.

PMID- 12234178
TI  - Systematic site-directed mutagenesis of human protein SRP54: interactions with
      signal recognition particle RNA and modes of signal peptide recognition.
AB  - The amino acid residues of human protein SRP54 which are required for binding to
      SRP RNA were identified by generating 40 nonoverlapping tri-alanine alterations
      within its methionine-rich M-domain (SRP54M). The mutant polypeptides were
      expressed in Escherichia coli, and their ability to bind to human and
      Methanococcus jannaschii SRP RNA were determined in vitro. Residues at positions
      379-387, 394-396, 400-405, and 409-411 of human SRP54 were within the predicted
      RNA binding site, and their alteration abolished the binding activities of the
      mutant polypeptides as expected. Changes at positions 418-423 had intermediate
      effects. Polypeptides containing mutations of 328-TLR-330 were inactive although
      these residues were far away from the presumed RNA binding site in the crystal
      structure of the free protein. Using the structures of the E. coli Ffh/4.5S core
      and of the human SRP54m dimer as templates, a molecular model of the complex
      between human SRP RNA helix 8 and a single SRP54M molecule was constructed in
      which Leucine 329 was positioned in closer proximity to the RNA binding domain.
      This representation was supported by studies of the SRP54m monomer/dimer ratio
      using gel filtration. The results were consistent with a change in the shape of
      the signal peptide binding groove upon binding of SRP54 to SRP RNA. We propose
      that the SRP RNA and a small region centered at a bulky nonpolar amino acid
      residue at position 329 of protein SRP54 play a critical role in the SRP
      dependent binding and release of signal peptides.

PMID- 12234179
TI  - Atomic force microscopy study of the effects of Mg(2+) and other divalent cations
      on the end-to-end DNA interactions.
AB  - Atomic force microscopy (AFM) was applied to directly visualize the end-to-end
      DNA interaction mediated by magnesium cations. We took advantage of the APS-mica,
      allowing the preparation of samples in a broad range of monovalent and divalent
      cations to separate the effects of Mg(2+) and Na(+) cations on the interaction of
      restriction DNA fragments with cohesive end. The AFM data clearly show that DNA
      restriction fragments with cohesive ends form substantial amount of circles in
      the presence of Mg(2+) cations, suggesting that Mg(2+) cations stabilize the
      interaction of cohesive ends. This effect depends on the MgCl(2) concentration,
      so that the yield of circles approaches 18% in the presence of 50 mM MgCl(2).
      Furthermore, we demonstrate that this conferred cohesive end stability is
      specific for divalent cations, as substitution of MgCl(2) with NaCl leads to a
      near complete loss of cohesive end stability. We further demonstrate that
      cohesive end stabilization is achieved by substituting Mg(2+) with Ca(2+),
      Mn(2+), or Zn(2+). The data obtained suggest that the end stabilization mediated
      by divalent cations is primarily the result of inter-base interactions rather
      than bridging of phosphate moieties.

PMID- 12234180
TI  - The relationship between ligand aggregation and G-quadruplex DNA selectivity in a
      series of 3,4,9,10-perylenetetracarboxylic acid diimides.
AB  - Human telomeres are comprised of d(TTAGGG) repeats that are capable of forming G
      quadruplex DNA structures. Ligands that bind to and stabilize these G-quadruplex
      DNA structures are potential inhibitors of the cancer cell-associated enzyme
      telomerase. Other potential biological uses of G-quadruplex targeting ligands
      have been proposed. One particularly challenging aspect of the contemplated uses
      of G-quadruplex targeting ligands is their selectivity for G-quadruplex DNA
      versus double-stranded DNA structures. We have previously reported the
      observation that two structurally related 3,4,9,10-perylenetetracarboxylic acid
      diimide-based G-quadruplex DNA ligands, PIPER [N,N'-bis(2-(1-piperidino)ethyl)
      3,4,9,10-perylenetetracarboxylic acid diimide] and Tel01 [N,N'-bis(3-(4
      morpholino)propyl)-3,4,9,10-perylenetetracarboxylic acid diimide], have different
      levels of G-quadruplex DNA binding selectivity at pH 7 as determined by
      absorbance changes in the presence of different DNA structures [Kerwin, S. M.,
      Chen, G., Kern, J. T., and Thomas, P. W. (2002) Bioorg. Med. Chem. Lett. 12, 447
      450]. Here we report that the less G-quadruplex DNA selective ligand PIPER can
      unwind double-stranded, closed circular plasmid DNA, as determined by a
      topoisomerase I assay. A model for the interaction of Tel01 with the G-quadruplex
      DNA structure formed by d(TAGGGTTA) was determined from NMR experiments. This
      model is similar to the previously published model for PIPER bound to the same G
      quadruplex DNA and failed to provide a structural basis for the observed
      increased selectivity of Tel01 interaction with G-quadruplex DNA. In contrast,
      investigation into the aggregation state of Tel01 and PIPER as well as other
      3,4,9,10-perylenetetracarboxylic acid diimide analogues bearing basic side chains
      demonstrates that ligand aggregation is correlated with G-quadruplex DNA binding
      selectivity. For all six analogues examined, those ligands that were aggregated
      at pH 7 in 70 mM potassium phosphate, 100 mM KCl, 1 mM EDTA buffer also
      demonstrated G-quadruplex DNA binding selectivity under these buffer conditions.
      Ligands that were not aggregated under these conditions display much lower levels
      of G-quadruplex DNA selectivity. The aggregation state of these ligands is
      extremely sensitive to the buffer pH. Tel01, which is aggregated at pH 7, is not
      aggregated at pH 6.4, where it demonstrates only modest G-quadruplex DNA binding
      selectivity, and PIPER in pH 8.5 buffer is both aggregated and highly G
      quadruplex DNA-selective. To our knowledge, these studies demonstrate the first
      DNA structure selectivity as achieved through pH-mediated ligand aggregation. The
      potential impact of these findings on the selectivity of other classes of G
      quadruplex DNA ligands is discussed.

PMID- 12234181
TI  - Single amino acid substitution in Bacillus sphaericus phenylalanine dehydrogenase
      dramatically increases its discrimination between phenylalanine and tyrosine
      substrates.
AB  - Homology-based modeling of phenylalanine dehydrogenases (PheDHs) from various
      sources, using the structures of homologous enzymes Clostridium symbiosum
      glutamate dehydrogenase and Bacillus sphaericus leucine dehydrogenase as a guide,
      revealed that an asparagine residue at position 145 of B. sphaericus PheDH was
      replaced by valine or alanine in PheDHs from other sources. This difference was
      proposed to be the basis for the poor discrimination by the B. sphaericus enzyme
      between the substrates L-phenylalanine and L-tyrosine. Residue 145 of this enzyme
      was altered, by site-specific mutagenesis, to hydrophobic residues alanine,
      valine, leucine, and isoleucine, respectively. The resultant mutants showed a
      high discrimination, above 50-fold, between L-phenylalanine and L-tyrosine. This
      higher specificity toward L-phenylalanine was due to K(m) values for L
      phenylalanine lowered more than 20-fold compared to the values for L-tyrosine.
      The greater specificity for L-phenylalanine in the wild-type Bacillus badius
      enzyme, which has a valine residue in the corresponding position, was also found
      to be largely due to a lower K(m) for this substrate. Activities were also
      measured with a range of six amino acids with aliphatic, nonpolar side chains,
      and with the corresponding oxoacids, and in all cases the specificity constants
      for these substrates were increased in the mutant enzymes. As with phenylalanine,
      these increases are mainly attributable to large decreases in K(m) values.

PMID- 12234182
TI  - The transmembrane domain of receptor-activity-modifying protein 1 is essential
      for the functional expression of a calcitonin gene-related peptide receptor.
AB  - Three receptor-activity-modifying proteins (RAMP) define specific interactions
      between calcitonin (CT) gene-related peptide (CGRP), adrenomedullin (AM) and
      amylin, and a CT receptor or a CT receptor-like receptor (CRLR). Both form
      heterodimeric RAMP/receptor complexes at the cell surface. This association
      represents a novel principle of G protein-coupled receptor function. RAMP1 is
      transported to the cell surface together with the CRLR or the CT receptor. Here,
      we have investigated the functional relevance of the short C-terminal
      intracellular tail QSKRTEGIV and of the single transmembrane domain of human (h)
      RAMP1 for their interactions with the hCRLR to constitute a CGRP receptor. To
      this end, hRAMP1 has been sequentially truncated from the C-terminus, and
      [(125)I]h alpha CGRP/hRAMP1/hCRLR association at the cell surface and cAMP
      accumulation in response to h alpha CGRP have been examined. With the C-terminal
      truncation of hRAMP1 by four amino acids wild-type hRAMP1 function was
      maintained, and the hCRLR was required for the transport of hRAMP1 to the cell
      surface. Further truncation of hRAMP1 through removal of the remaining five
      intracellular amino acids revealed CRLR-independent cell surface delivery but
      otherwise normal hRAMP1 activity. Sequential shortening of the hRAMP1
      transmembrane domain resulted in progressively impaired association with the
      hCRLR and, as a consequence, abolished CGRP receptor function. In conclusion, the
      intracellular QSKRT sequence adjacent to the transmembrane domain of hRAMP1
      provides a signal for intracellular retention. The sequence is unrelated to
      consensus endoplasmic reticulum retention/retrieval motives and overridden by the
      presence of the hCRLR. The entire single transmembrane domain of hRAMP1 together
      with one hydrophilic amino acid residue at its C-terminus is required for the
      formation of a fully functional CGRP/hRAMP1/hCRLR receptor complex.

PMID- 12234183
TI  - Fe(2+)-catalyzed oxidation and cleavage of sarcoplasmic reticulum ATPase reveals
      Mg(2+) and Mg(2+)-ATP sites.
AB  - Fe(2+) can substitute for Mg(2+) in activation of the sarcoplasmic reticulum (SR)
      ATPase, permitting approximately 25% activity in the presence of Ca(2+).
      Therefore, we used Fe(2+) to obtain information on the binding sites for Mg(2+)
      and the Mg(2+)-ATP complex within the enzyme structure. When the ATPase is
      incubated with Fe(2+) in the presence of H(2)O(2) and/or ascorbate, specific
      patterns of Fe(2+)-catalyzed oxidation and cleavage are observed in the SR
      ATPase, depending on its Ca(2+)-bound (E1-Ca(2)) or Ca(2+)-free conformation (E2
      TG), as well as on the presence of ATP. The ATPase protein in the E1-Ca(2) state
      is cleaved efficiently by Fe(2+) with H(2)O(2) and ascorbate assistance, yielding
      a 70-75 kDa carboxyl end fragment. Cleavage of the ATPase protein in the E2-TG
      state occurs within the same region, but with a more diffuse pattern, yielding
      multiple fragments within the 65-85 kDa range. When Fe(2+) catalysis is assisted
      by ascorbate only (in the absence of H(2)O(2)), cleavage at the same protein site
      occurs much more slowly, and is facilitated by ATP (or AMP-PNP) and Ca(2+). Amino
      acid sequencing indicates that protein cleavage occurs at and near Ser346, and is
      attributed to Fe(2+) bound to a primary Mg(2+) site near Ser346 and neighboring
      Glu696. In addition, incubation with Fe(2+) and ascorbate produces Ca(2+)- and
      ATP-dependent oxidation of the Thr441 side chain, as demonstrated by NaB(3)H(4)
      incorporation and analysis of fragments obtained by extensive trypsin digestion.
      This oxidation is attributed to bound Fe(2+)-ATP complex, as shown by structural
      modeling of the Mg(2+)-ATP complex at the substrate site.

PMID- 12234185
TI  - Solution structure and phosphopeptide binding to the N-terminal domain of
      Yersinia YopH: comparison with a crystal structure.
AB  - Virulence of pathogenic bacteria of the genus Yersinia requires the injection of
      six effector proteins into the cytoplasm of host cells. The amino-terminal domain
      of one of these effectors, the tyrosine phosphatase YopH, is essential for
      translocation of YopH, as well as for targeting it to phosphotyrosine-containing
      substrates of the type pYxxP. We report the high-resolution solution structure of
      the N-terminal domain (residues 1-129) from the Yersinia pseudotuberculosis YopH
      (YopH-NT) in complex with N-acetyl-DEpYDDPF-NH(2), a peptide derived from an in
      vivo protein substrate. In contrast to the domain-swapped dimer observed in a
      crystal structure of the same protein (Smith, C. L., Khandelwal, P., Keliikuli,
      K., Zuiderweg, E. R. P., and Saper, M. A. (2001) Mol. Microbiol. 42, 967-979),
      YopH-NT is monomeric in solution. The peptide binding site is located on a beta
      hairpin that becomes the crossover point in the dimer structure. The binding site
      has several characteristics that are reminiscent of SH2 domains, which also bind
      to pYxxP sequences.

PMID- 12234184
TI  - C2 domains of protein kinase C isoforms alpha, beta, and gamma: activation
      parameters and calcium stoichiometries of the membrane-bound state.
AB  - The independently folding C2 domain motif serves as a Ca(2+)-dependent membrane
      docking trigger in a large number of Ca(2+) signaling pathways. A comparison was
      initiated between three closely related C2 domains from the conventional protein
      kinase C subfamily (cPKC, isoforms alpha, beta, and gamma). The results reveal
      that these C2 domain isoforms exhibit some similarities but are specialized in
      important ways, including different Ca(2+) stoichiometries. In the absence of
      membranes, Ca(2+) affinities of the isolated C2 domains are similar (2-fold
      difference) while Hill coefficients reveal cooperative Ca(2+) binding for the PKC
      beta C2 domain but not for the PKC alpha or PKC gamma C2 domain (H = 2.3 +/- 0.1
      for PKC beta, 0.9 +/- 0.1 for PKC alpha, and 0.9 +/- 0.1 for PKC gamma). When
      phosphatidylserine-containing membranes are present, Ca(2+) affinities range from
      the sub-micromolar to the micromolar (7-fold difference) ([Ca(2+)](1/2) = 0.7 +/-
      0.1 microM for PKC gamma, 1.4 +/- 0.1 microM for PKC alpha, and 5.0 +/- 0.2
      microM for PKC beta), and cooperative Ca(2+) binding is observed for all three C2
      domains (Hill coefficients equal 1.8 +/- 0.1 for PKC beta, 1.3 +/- 0.1 for PKC
      alpha, and 1.4 +/- 0.1 for PKC gamma). The large effects of membranes are
      consistent with a coupled Ca(2+) and membrane binding equilibrium, and with a
      direct role of the phospholipid in stabilizing bound Ca(2+). The net negative
      charge of the phospholipid is more important to membrane affinity than its
      headgroup structure, although a slight preference for phosphatidylserine is
      observed over other anionic phospholipids. The Ca(2+) stoichiometries of the
      membrane-bound C2 domains are detectably different. PKC beta and PKC gamma each
      bind three Ca(2+) ions in the membrane-associated state; membrane-bound PKC alpha
      binds two Ca(2+) ions, and a third binds weakly or not at all under physiological
      conditions. Overall, the results indicate that conventional PKC C2 domains first
      bind a subset of the final Ca(2+) ions in solution, and then associate weakly
      with the membrane and bind additional Ca(2+) ions to yield a stronger membrane
      interaction in the fully assembled tertiary complex. The full complement of
      Ca(2+) ions is needed for tight binding to the membrane. Thus, even though the
      three C2 domains are 64% identical, differences in Ca(2+) affinity,
      stoichiometry, and cooperativity are observed, demonstrating that these closely
      related C2 domains are specialized for their individual functions and contexts.

PMID- 12234186
TI  - The Ff gene 5 single-stranded DNA-binding protein binds to the transiently folded
      form of an intramolecular G-quadruplex.
AB  - The Ff gene 5 protein (g5p) is classified as a single-stranded DNA-binding
      protein. However, we previously showed that g5p binds with high affinity to a
      SELEX-selected G-rich 58-mer DNA oligomer, I-3, that forms an intramolecular G
      quadruplex [Wen, J.-D., Gray, C. W., and Gray, D. M. (2001) Biochemistry 40, 9300
      9310]. In 200 mM NaCl at 37 degrees C, g5p binds to I-3 in two stages, the first
      stage being the formation of a discrete intermediate complex that appears to be a
      precursor to a saturated g5p x I-3 complex. For the present paper, CD
      spectroscopy and DMS methylation techniques were used to investigate the binding
      of g5p to the I-3 oligomer and to the truncated 26-nucleotide core of the I-3
      oligomer. The core sequence, called I-3c26, was d(GGGGTCAGGCTGGGGTTGTGCAGGTC).
      Results were the following: (1) The g5p binds in one stage to I-3c26 in 200 mM
      NaCl at 37 degrees C. (2) The intermediate complex of g5p.I-3 is formed by the
      binding of g5p to the core sequence. (3) G-quadruplex structures are maintained
      in both the g5p x I-3 and g5p x I-3c26 complexes, but the bound G-quadruplex
      structures are altered from their respective steady-state folded forms in 200 mM
      NaCl. (4) CD kinetics measurements showed that the I-3c26 quadruplex folds in two
      stages and that a transiently folded form is apparently the same as the altered
      structure to which g5p binds. (5) DMS methylation protection and interference
      experiments identified two guanines that are differentially involved in the
      steady-state folded and g5p-bound G-quadruplex structures. A model for a possible
      I-3c26 G-quadruplex structure is described.

PMID- 12234187
TI  - Pheophytin-protein interactions in photosystem II studied by resonance Raman
      spectroscopy of modified reaction centers.
AB  - Soret-excited resonance Raman spectra of two types of pheophytin-exchanged
      photosystem II RCs are reported. The cofactor composition of the reaction centers
      was modified by exchanging pheophytin a for 13(1)-deoxo-13(1)-hydroxypheophytin
      a, yielding one preparation with selective replacement of the photochemically
      inactive pheophytin (H(B)) and a second one exhibiting total replacement of H(B)
      and 40% replacement of H(A), the primary electron acceptor. Resonance Raman
      spectra indicate that the other bound cofactors present are not significantly
      perturbed by Pheo substitution. The resonance Raman contributions from H(A) and
      H(B) in the carbonyl stretching region are identified at 1679 and 1675 cm(-)(1),
      respectively, indicating that both pheophytin molecules in the photosystem II
      reaction center have hydrogen-bonded keto-carbonyl groups. This conclusion
      differs from what is observed in the functionally related RCs of purple non
      sulfur bacteria, where the keto-carbonyl group of H(B) is not hydrogen bonded,
      but confirms predictions from models based on protein sequence alignments.

PMID- 12234189
TI  - Identification of oxidized derivatives of neuroketals.
AB  - Oxidative stress and protein aggregation have been implicated in the pathogenesis
      of neurodegenerative diseases. The formation of neuroprostanes, isoprostane-like
      compounds formed from oxidation of docosahexaenoic acid, which is uniquely
      enriched in the brain, is increased in Alzheimer's disease. We recently
      identified the formation of a new class of highly reactive gamma-keto aldehydes,
      neuroketals, in vivo as products of the neuroprostane pathway. Neuroketals adduct
      to lysine residues of proteins with remarkable rapidity and induce cross-linking.
      Because neuroketals have either a 1,4-pentadiene or 1,4,7-octatriene side chain
      structure, we hypothesized that they could undergo further oxidation to form
      neuroketals with an additional hydroxyl group. Oxidation of docosahexaenoic acid
      in vitro yielded a series of compounds that were confirmed to be oxidized
      neuroketals by mass spectrometric analyses. Analysis of oxidized neuroketal
      adducts during oxidation of docosahexaenoic acid in the presence of lysine
      revealed the formation of oxidized Schiff base and hydroxylactam adducts.
      Oxidized hydroxylactam neuroketal-lysyl protein adducts, analyzed after digestion
      of proteins to individual amino acids, were not detected in nonoxidized rat brain
      synaptosomes but were readily detected following oxidation of synaptosomes. These
      studies indicate that neuroketals can undergo further oxidation, which in turn
      suggests that measurement of only unoxidized neuroketal adducts likely
      underestimates the amount of neuroketal adducts present in the brain in disorders
      of oxidant stress.

PMID- 12234188
TI  - Histidine 190-D1 and glutamate 189-D1 provide structural stabilization in
      photosystem II.
AB  - In photosynthesis, photosystem II (PSII) conducts the light-driven oxidation of
      water to oxygen. Tyrosine Z is Tyr 161 of the D1 polypeptide; Z acts as an
      intermediary electron carrier in water oxidation. In this report, EPR
      spectroscopy was used to study the effect of His 190 and Glu 189 on Z* yield and
      reduction kinetics. Neither mutation has a significant impact on the EPR line
      shape of Z*. At room temperature and pH 7.5, the E189Q-D1 mutation has a single
      turnover Z* yield that is 84% compared to wild-type. The H190Q-D1 mutation
      decreases the Z* yield at room temperature by a factor of 2.6 but has a more
      modest effect (factor of 1.6) at -10 degrees C. The temperature dependence is
      shown to be primarily reversible. Neither mutation has a dramatic effect on Z*
      decay kinetics. The Z* minus Z FT-IR spectrum, recorded at pH 7.5 on H190Q,
      reveals perturbations, including an increased spectral contribution from a PSII
      chlorophyll. The Z* minus Z FT-IR spectrum, recorded at pH 7.5 on E189Q, shows
      perturbations, including a decreased contribution from the carboxylate side chain
      of a glutamate or aspartate. Temperature-dependent changes in H190Q-D1 and E189Q
      D1 Z. yield are attributed to a reversible conformational change, which alters
      the electron-transfer rate from Z to P(680)(+). On the basis of these results, we
      conclude that H190 and E189 play a role in the structural stabilization of PSII.
      We postulate that some or all of the phenotypic changes observed in H190Q and
      E189Q mutants may be caused by structural alterations in PSII.

PMID- 12234190
TI  - Site-specific incorporation of (aminooxy)acetic acid into proteins.
AB  - By employing a general biosynthetic method for the elaboration of proteins
      containing unnatural amino acid analogues, we incorporated (aminooxy)acetic acid
      into positions 10 and 27 of Escherichia coli dihydrofolate reductase.
      Introduction of the modified amino acid into DHFR was accomplished in an in vitro
      protein biosynthesizing system by readthrough of a nonsense (UAG) codon with a
      suppressor tRNA that had been activated with (aminooxy)acetic acid. Incorporation
      of the amino acid proceeded with reasonable efficiency at codon position 10 but
      less well at position 27. (Aminooxy)acetic acid was also incorporated into
      position 72 of DNA polymerase beta. Peptides containing (aminooxy)acetic acid
      have been shown to adopt a preferred conformation involving an eight-membered
      ring that resembles a gamma-turn. Accordingly, the present study may facilitate
      the elaboration of proteins containing conformationally biased peptidomimetic
      motifs at predetermined sites. The present results further extend the examples of
      ribosomally mediated formation of peptide bond analogues of altered connectivity
      and provide a conformationally biased linkage at a predetermined site. It has
      also been shown that the elaborated protein can be cleaved chemically at the site
      containing the modified amino acid.

PMID- 12234191
TI  - Regulation of ganglioside biosynthesis by enzyme complex formation of
      glycosyltransferases.
AB  - Three key regulatory enzymes in ganglioside biosynthesis, sialyltransferase I
      (ST1), sialyltransferase II (ST2), and N-acetylgalactosaminyltransferase I
      (GalNAcT), have been expressed as fusion proteins with green, yellow, or red
      fluorescent protein (GFP, YFP, or RFP) in F-11A cells. F-11A cells are a
      substrain of murine neuroblastoma F-11 cells that contain only low endogenous ST2
      and GalNAcT activity. The subcellular localization of the fusion proteins has
      been determined by fluorescence microscopy, and the ganglioside composition of
      these cells was analyzed by high-performance thin-layer chromatography (HPTLC).
      ST2-GFP (85 kDa) shows a distinct Golgi localization, whereas ST1-YFP (85 kDa)
      and GalNAcT-RFP (115 kDa) are broadly distributed in ER and Golgi. Untransfected
      F-11A cells contain mainly GM3, whereas stable transfection with ST2 or GalNAcT
      results in the predominant expression of b-series complex gangliosides (BCGs).
      This result indicates that the expression of ST2 enhances the activity of
      endogenous GalNAcT and vice versa. The specificity of this reaction has been
      verified by in vitro activity assays with detergent-solubilized enzymes,
      suggesting the formation of an enzyme complex between ST2 and GalNAcT but not
      with ST1. Complex formation has also been verified by co-immunoprecipitation of
      ST2-GFP upon transient transfection with GalNAcT-HA-RFP and by GFP-to-RFP FRET
      signals that are confined to the Golgi. FRET analysis also suggests that ST2-GFP
      binds tightly to pyrene-labeled GM3 but not to ST1. We hypothesize that an ST2
      GM3 complex is associated with GalNAcT, resulting in the enhanced conversion of
      GM3 to GD3 and BCGs in the Golgi. Taken together, our results support the concept
      that ganglioside biosynthesis is tightly regulated by the formation of
      glycosyltransferase complexes in the ER and/or Golgi.

PMID- 12234192
TI  - Role of disulfide bonds in folding and activity of leiurotoxin I: just two
      disulfides suffice.
AB  - The aim of this study is to investigate the contribution of each disulfide bond
      in the folding and function of leiurotoxin I, a short scorpion toxin that blocks
      small conductance K(+) channels. The structure of leiurotoxin I contains a motif
      conserved in all scorpion toxins, formed by a helix and a double-stranded beta
      sheet and stabilized by three disulfide bridges. We synthesized three analogues,
      each presenting two alpha-aminobutyric acid (Abu) moieties replacing two bridged
      cysteine residues: LeTx1 ([Abu 3,21] Leiurotoxin I), LeTx2 ([Abu 8,26]
      Leiurotoxin I), and LeTx3 ([Abu 12,28] Leiurotoxin I). All three analogues fold
      into a major product containing two native disulfide bonds, while LeTx3 forms an
      additional isomer, containing non-native disulfides. In denaturing conditions,
      analogues LeTx2 and LeTx3 yield non-native isomers, while LeTx1 only forms the
      isomer with native disulfides. All isomers with native disulfides contain
      nativelike alpha-helical conformations and bind to synaptosomal membranes with
      affinities within a log of that shown by the native toxin. By contrast, the non
      native LeTx3A analogue exhibits a disordered conformation and a decreased
      biological potency. Our results indicate that the "CxxxC, CxC" cysteine spacing,
      conserved in all scorpion toxins and preserved in LeTx1, may play an active role
      in folding, and that only two native disulfide bonds in leiurotoxin I are
      sufficient to preserve a nativelike and active conformation. Thus, in the
      scorpion toxin scaffold, modifications of conserved and interior cysteine
      residues may permit modulation of function, without significantly affecting
      folding efficiency and structure.

PMID- 12234193
TI  - Role of tyrosine-103 in myoglobin peroxidase activity: kinetic and steady-state
      studies on the reaction of wild-type and variant recombinant human myoglobins
      with H(2)O(2).
AB  - Myoglobin (Mb) catalyzes a range of oxidation reactions in the presence of
      hydrogen peroxide (H(2)O(2)) through a peroxidase-like cycle. C110A and Y103F
      variants of human Mb have been constructed to assess the effects of removing
      electron-rich oxidizable amino acids from the protein on the peroxidase activity
      of Mb: a point mutation at W14 failed to yield a viable protein. Point mutations
      at C110 and Y103 did not result in significant changes to structural elements of
      the heme pocket, as judged by low-temperature electron paramagnetic spectroscopy
      (EPR) studies on the ground-state ferric proteins. However, compared to the
      native protein, the yield of globin radical (globin*) was significantly decreased
      for the Y103F but not the C110A variant Mb upon reaction of the respective
      proteins with H(2)O(2). In contrast with our expectation that inhibiting pathways
      of intramolecular electron transfer may lead to enhanced Mb peroxidase activity,
      mutation of Y103 marginally decreased the rate constant for reaction of Mb with
      H(2)O(2) (1.4-fold) as judged by stopped-flow kinetic analyses. Consistent with
      this decrease in rate constant, steady-state analyses of Y103F Mb-derived
      thioanisole sulfoxidation indicated decreased V(max) and increased K(m) relative
      to the wild-type control. Additionally, thioanisole sulfoxidation proceeded with
      lower stereoselectivity, suggesting that Y103 plays a significant role in
      substrate binding and orientation in the heme pocket of Mb. Together, these
      results show that electron transfer within the globin portion of the protein is
      an important modulator of its stability and catalytic activity. Furthermore, the
      hydrogen-bonding network involving the residues that line the heme pocket of Mb
      is crucial to both efficient peroxidase activity and stereospecificity.

PMID- 12234194
TI  - Irreversible inactivation of soybean lipoxygenase-1 by hydrophobic thiols.
AB  - Soybean lipoxygenase-1 is inactivated by micromolar concentrations of the
      following hydrophobic thiols: 1-octanethiol, 12(S)-mercapto-9(Z)-octadecenoic
      acid (S-12-HSODE), 12(R)-mercapto-9(Z)-octadecenoic acid (R-12-HSODE), and 12
      mercaptooctadecanoic acid (12-HSODA). In each case, inactivation is time
      dependent and not reversed by dilution or dialysis. Inactivation requires 13
      hydroperoxy-9(Z),11(E)-octadecadienoic acid (13-HPOD), which suggests that it is
      specific for the ferric form of the enzyme. Lipoxygenase catalyzes an oxygenation
      reaction on each of the aforementioned thiols, as judged by the consumption of
      O(2). These reactions also require 13-HPOD. 1-Octanethiol is converted to 1
      octanesulfonic acid, which was identified by GC/MS of its methyl ester. The rates
      of oxygen uptake for R- and S-12-HODE are about 5- and 2.5-fold higher than the
      rate with 1-octanethiol. The stoichiometries of inactivation imply that
      inactivation occurs on approximately 1 in 18 turnovers for 12-HSODA, 1 in 48
      turnovers for 1-octanethiol, 1 in 63 turnovers for S-12-HSODE, and 1 in 240
      turnovers for R-12-HSODE. These data imply that close resemblance to lipoxygenase
      substrates is not a crucial requirement for either oxidation or inactivation.
      Under the conditions of our experiments, inactivation was not observed with
      several more polar thiols: mercaptoethanol, dithiothreitol, L-cysteine,
      glutathione, N-acetylcysteamine, and captopril. The results imply that
      hydrophobic thiols irreversibly inactivate soybean lipoxygenase by a mechanism
      that involves oxidation at sulfur.

PMID- 12234195
TI  - Regulation of lipid composition in Acholeplasma laidlawii and Escherichia coli
      membranes: NMR studies of lipid lateral diffusion at different growth
      temperatures.
AB  - Lipid lateral diffusion coefficients have been directly determined by pulsed
      field gradient NMR spectroscopy on macroscopically aligned, fully hydrated
      lamellar phases containing dimyristoylphosphatidylcholine and total lipid
      extracts from Acholeplasma laidlawii and Escherichia coli. The temperature
      dependence of the diffusion coefficient was of the Arrhenius type in the
      temperature interval studied. The sharp increase in the diffusion coefficient at
      the growth temperature of E. coli obtained by FRAP measurements, using a
      fluorescent probe molecule (Jin, A. J., Edidin, M., Nossal, R., and Gershfeld, N.
      L. (1999) Biochemistry 38, 13275-13278), was not observed. Thus, we conclude that
      the lipid structural properties (i.e., those affecting the lipid phase behavior),
      rather than the lipid dynamics, are involved in the adjustment of the membrane
      lipid composition. Further support for this conclusion is given by the finding
      that lipid extracts from A. laidlawii grown at different temperatures have about
      the same diffusion coefficients. Finally, the lipid lateral diffusion in bilayers
      of phospholipids was found to be much faster than that in bilayers of mainly
      glucolipids, which can be understood in terms of a free volume theory for the
      diffusion process.

PMID- 12234197
TI  - Green chemistry.

PMID- 12234198
TI  - Origins, current status, and future challenges of green chemistry.
AB  - Over the course of the past decade, green chemistry has demonstrated how
      fundamental scientific methodologies can protect human health and the environment
      in an economically beneficial manner. Significant progress is being made in
      several key research areas, such as catalysis, the design of safer chemicals and
      environmentally benign solvents, and the development of renewable feedstocks.
      Current and future chemists are being trained to design products and processes
      with an increased awareness for environmental impact. Outreach activities within
      the green chemistry community highlight the potential for chemistry to solve many
      of the global environmental challenges we now face. The origins and basis of
      green chemistry chart a course for achieving environmental and economic
      prosperity inherent in a sustainable world.

PMID- 12234199
TI  - On inventing reactions for atom economy.
AB  - An important first step in making organic reactions more environmentally benign
      by design requires processes that are, to a first approximation, simple additions
      with anything else needed only catalytically. Since so few of the existing
      reactions are additions, synthesis of complex molecules requires the development
      of new atom-economic methodology. The prospect for such developments is probed in
      the context of ruthenium-catalyzed reactions. Using mechanistic reasoning, over
      20 new processes of varying complexity have been designed and implemented. While
      some involved oxidation-reduction processes, most involved C-C bond-forming
      reactions.

PMID- 12234200
TI  - The chemistry of dimethyl carbonate.
AB  - Dimethyl carbonate (DMC) is a versatile compound that represents an attractive
      eco-friendly alternative to both methyl halides (or dimethyl sulfate) and
      phosgene for methylation and carbonylation processes, respectively. In fact, the
      reactivity of DMC is tunable: at T = 90 degrees C, methoxycarbonylations take
      place, whereas at higher reaction temperatures, methylation reactions are
      observed with a variety of nucleophiles. In the particular case of substrates
      susceptible to multiple alkylations (e.g., CH(2)-active compounds and primary
      amines), DMC allows unprecedented selectivity toward mono-C- and mono-N
      methylation reactions. Nowadays produced by a clean process, DMC possesses
      properties of nontoxicity and biodegradability which makes it a true green
      reagent to use in syntheses that prevent pollution at the source. Moreover, DMC
      mediated methylations are catalytic reactions that use safe solids (alkaline
      carbonates or zeolites), thereby avoiding the formation of undesirable inorganic
      salts as byproducts. The reactivity of other carbonates is reported as well:
      higher homologues of DMC (i.e., diethyl and dibenzyl carbonate), are excellent
      mono-C- and mono-N-alkylating agents, whereas asymmetrical methyl alkyl
      carbonates (ROCO(2)Me with R > or = C(3)) undergo methylation processes with a
      chemoselectivity up to 99%.

PMID- 12234201
TI  - Microwave-accelerated homogeneous catalysis in organic chemistry.
AB  - The efficiency of microwave flash heating in accelerating organic transformations
      (reaction times reduced from days and hours to minutes and seconds) has recently
      been proven in several different fields of organic chemistry. This specific
      account mainly summarizes our own experiences in developing rapid, robust, and
      selective microwave-assisted transition metal-catalyzed homogeneous reactions.
      Applications include selective Heck couplings, cross-couplings, and asymmetric
      substitutions. The science of green chemistry was developed to meet the
      increasing demand for environmentally benign chemical processes. We believe the
      combination of metal catalysis and microwave heating will be of importance in the
      search for green laboratory-scale synthesis.

PMID- 12234203
TI  - Aqueous biphasic hydrogenations.
AB  - In addition to the useful physical properties of biphasic systems (easy
      separation of products and catalyst, facile catalyst reuse) aqueous media may
      largely influence the chemistry of catalytic reactions. By appropriate pH
      manipulations, the selectivity of hydrogenation of unsaturated aldehydes with
      ruthenium(II) phosphine catalysts was controlled from the exclusive formation of
      saturated aldehydes to that of unsaturated alcohols. Phase separation of the
      constituents of catalytic systems eliminated substrate inhibition (hydrogenation
      of aldehydes) and helped formation of catalytically active species
      ([RhH(PPh(3))(3)] from [RhCl(PPh(3))(3)] in hydrogenation of acetophenone). The
      reactive nature of H(2)O was revealed by fast catalysis of H/D exchange and
      deuteration processes.

PMID- 12234202
TI  - Unsaturated O- and N-heterocycles from carbohydrate feedstocks.
AB  - With reference to the impending transition of chemical industry from depleting
      fossil raw materials to renewable feedstocks--the end of cheap oil is predicted
      for 2040 at the latest--this account gives an overview on chemically transforming
      carbohydrates, by far the major part of the annually regrowing biomass, into the
      following unsaturated O- and N-heterocycles with versatile industrial application
      profiles: furans, pyrans, dihydropyranones, pyrroles, pyrazoles, imidazoles,
      pyridinols, pyrazines, and quinoxalines. Although the emphasis was laid on
      conversions that can be effected in practical one-pot procedures or in a few
      large-scale-adaptable steps, a broad structural variety of products emerges that
      have not only diverse chemical functionalities but also hydrophilic "residual
      sugar" portions that render them water-soluble and readily biodegradable.

PMID- 12234204
TI  - Supercritical carbon dioxide as a green reaction medium for catalysis.
AB  - Carbon dioxide in its liquid or supercritical state (scCO(2)) has a prodigious
      potential as an environmentally benign reaction medium for sustainable chemical
      synthesis. Since the mid-1990s, rapidly increasing research efforts have shown
      that scCO(2) can replace conventional and potentially hazardous solvents in a
      wide range of processes. There is also increasing evidence that the application
      of scCO(2) can broaden the scope of catalytic synthetic methodologies. On the
      basis of the experience in our laboratories, this report analyzes the impact of
      scCO(2) on green organometallic catalysis.

PMID- 12234206
TI  - 2-Arylindene metallocenes: conformationally dynamic catalysts to control the
      structure and properties of polypropylenes.
AB  - Polymerization of propylene with catalysts derived from unbridged 2-arylindene
      metallocenes leads to elastomeric, low-tacticity polypropylenes. The
      polymerization behavior of these conformationally dynamic catalyst systems is
      interpreted in terms of a multistate mechanism where the catalyst enchains the
      monomer from both stereoselective and nonstereoselective conformations during the
      lifetime of a single polymer chain. The structure and properties of the
      polypropylenes depend sensitively on the metallocene and the polymerization
      conditions (temperature, pressure, monomer concentration); samples of low to
      intermediate isotacticity ([mmmm] = 20-40%) are elastomeric, with low densities
      and broad melting ranges that extend to 150 degrees C. Samples of higher
      tacticity ([mmmm] = 40-70%) behave as softened thermoplastics.

PMID- 12234205
TI  - H(2)O(2) in CO(2): sustainable production and green reactions.
AB  - Hydrogen peroxide is a "green" oxidant whose relatively high cost has prevented
      it from being applied to commodity chemical processing. Interestingly, those
      attributes of the current H(2)O(2) process that contribute to the high cost also
      contribute to its nonsustainable features. We have consequently explored the
      generation of hydrogen peroxide both by the AQ route and directly from hydrogen
      and oxygen using liquid CO(2) as the solvent, because CO(2) provides some unique
      advantages to H(2)O(2) synthesis.

PMID- 12234207
TI  - Green, catalytic oxidations of alcohols.
AB  - Three methods are described, in the context of the guiding principles of green
      chemistry, for the catalytic oxidation of alcohols. The first employs a
      recyclable oligomeric TEMPO catalyst (PIPO) and sodium hypochlorite as the
      oxidant in a bromide-free and chlorinated hydrocarbon solvent-free system. The
      second involves a ruthenium/TEMPO catalyst and oxygen as the oxidant. The third
      consists of a recyclable water-soluble palladium-diamine complex in conjunction
      with air as the oxidant in an aqueous biphasic system. The mechanisms of the
      ruthenium/TEMPO- and palladium-catalyzed oxidations are discussed, and the
      mechanism of the former is compared with that of the analogous copper/TEMPO
      catalyst.

PMID- 12234208
TI  - TAML oxidant activators: a new approach to the activation of hydrogen peroxide
      for environmentally significant problems.
AB  - In the Institute for Green Oxidation Chemistry, we develop oxidation catalysts
      with useful lifetimes via an iterative design process in which oxidation
      sensitive ligand groups are identified and replaced. The process has led to
      catalysts with greatly enhanced stability toward oxidative and hydrolytic
      degradation. The iron catalysts described herein can be comprised exclusively of
      biochemically common elements. They are efficient and selective peroxide
      activators for many areas of technology. They are water-soluble and are effective
      in minute quantities (nanomolar to low micromolar) over a broad pH range. Various
      green chemistry applications are sketched.

PMID- 12234209
TI  - Solid acids for green chemistry.
AB  - Solid acids and especially those based on micelle-templated silicas and other
      mesoporous high surface area support materials are beginning to play a
      significant role in the greening of fine and specialty chemicals manufacturing
      processes. A wide range of important organic reactions can be efficiently
      catalyzed by these materials, which can be designed to provide different types of
      acidity as well as high degrees of reaction selectivity. The solid acids
      generally have high turnover numbers and can be easily separated from the organic
      components. The combination of this chemistry with innovative reaction
      engineering offers exciting opportunities for innovative green chemical
      manufacturing in the future.

PMID- 12234210
TI  - The use of ultra- and nanofiltration techniques in homogeneous catalyst
      recycling.
AB  - In recent years, the application of membrane technology in homogeneous catalyst
      recycling has received widespread attention. This technology offers a solution
      for the major drawback of homogeneous catalysis, that is, recycling of the
      catalyst. From both an environmental and an industrial point of view, this
      technology is very interesting, since it allows the future application of
      homogeneous catalysts in the synthesis of commercial products, leading to faster,
      cleaner and highly selective green industrial processes. In this account, an
      overview is given of the promising results obtained in the field of homogeneous
      catalyst recycling using nanofiltration membrane technology.

PMID- 12234211
TI  - Real-time electrochemical monitoring: toward green analytical chemistry.
AB  - This Account presents a survey of recent advances in electrochemical sensing
      technology relevant to green analytical chemistry and examines the potential
      advantages, limitations, and applications of these monitoring devices. Stricter
      environmental control and effective process monitoring have created considerable
      demands for innovative analytical methodologies. New devices and protocols, with
      negligible waste generation or no hazardous substances, and in situ real-time
      monitoring capability are particularly needed for addressing the challenges of
      green analytical chemistry. The coupling of modern electrochemical detection
      principles with recent advances in molecular recognition, microelectronics, and
      microfabrication has led to powerful, compact, and "user-friendly" analytical
      devices. The unique features of such electrochemical monitoring systems make them
      particularly attractive for addressing environmental and industrial problems and
      the challenges of green chemistry. These developments allow the instrument to be
      taken to the sample (rather than the traditional way of bringing the sample to
      the laboratory) and hence to ensure effective process or pollution control.

PMID- 12234212
TI  - A piece of my mind. The three-legged stool.

PMID- 12234213
TI  - Sewage yields clues to SV40 transmission.

PMID- 12234214
TI  - Multifaceted treatment aids depressed young.

PMID- 12234219
TI  - Testing for human papillomavirus in women with abnormal pap smear results.

PMID- 12234220
TI  - Testing for human papillomavirus in women with abnormal pap smear results.

PMID- 12234222
TI  - Long-term pulmonary consequences of elective cesarean delivery.

PMID- 12234224
TI  - Diagnosing temporal arteritis.

PMID- 12234225
TI  - Diagnosing temporal arteritis.

PMID- 12234227
TI  - Malpractice risk and patient complaints.

PMID- 12234229
TI  - Prognosis for gross motor function in cerebral palsy: creation of motor
      development curves.
AB  - CONTEXT: Lack of a valid classification of severity of cerebral palsy and the
      absence of longitudinal data on which to base an opinion have made it difficult
      to consider prognostic issues accurately. OBJECTIVE: To describe patterns of
      gross motor development of children with cerebral palsy by severity, using
      longitudinal observations, as a basis for prognostic counseling with parents and
      for planning clinical management. DESIGN: Longitudinal cohort study of children
      with cerebral palsy, stratified by age and severity of motor function and
      observed serially for up to 4 years during the period from 1996 to 2001. SETTING:
      Nineteen publicly funded regional children's ambulatory rehabilitation programs
      in Ontario. PARTICIPANTS: A total of 657 children aged 1 to 13 years at study
      onset, representing the full spectrum of clinical severity of motor impairment in
      children with cerebral palsy. MAIN OUTCOME MEASURES: Severity of cerebral palsy,
      classified with the 5-level Gross Motor Function Classification System; function,
      formally assessed with the Gross Motor Function Measure (GMFM). RESULTS: Based on
      a total of 2632 GMFM assessments, 5 distinct motor development curves were
      created; these describe important and significant differences in the rates and
      limits of gross motor development among children with cerebral palsy by severity.
      There is substantial within-stratum variation in gross motor development.
      CONCLUSIONS: Evidence-based prognostication about gross motor progress in
      children with cerebral palsy is now possible, providing parents and clinicians
      with a means to plan interventions and to judge progress over time. Further work
      is needed to describe motor function of adolescents with cerebral palsy.

PMID- 12234230
TI  - Ultrasound-guided extracorporeal shock wave therapy for plantar fasciitis: a
      randomized controlled trial.
AB  - CONTEXT: Extracorporeal shock wave therapy (ESWT) is increasingly used for
      plantar fasciitis, but limited evidence supports its use. OBJECTIVE: To determine
      whether ultrasound-guided ESWT reduces pain and improves function in patients
      with plantar fasciitis. DESIGN: Double-blind, randomized, placebo-controlled
      trial conducted between April 1999 and June 2001. SETTING: Participants were
      recruited from the community-based referring physicians (primary care physicians,
      rheumatologists, orthopedic surgeons, and sports physicians) of a radiology group
      in Melbourne, Australia. PARTICIPANTS: We screened 178 patients and enrolled 166;
      160 completed the 15-week protocol. Entry criteria included age at least 18 years
      with plantar fasciitis, defined as heel pain maximal over the plantar aspect of
      the foot of at least 6 weeks' duration, and an ultrasound-confirmed lesion,
      defined as thickening of the origin of the plantar fascia of at least 4 mm,
      hypoechogenicity, and alterations in the normal fibrillary pattern.
      INTERVENTIONS: Patients were randomly assigned to receive either ultrasound
      guided ESWT given weekly for 3 weeks to a total dose of at least 1000 mJ/mm(2) (n
      = 81), or identical placebo to a total dose of 6.0 mJ/mm(2) (n = 85). MAIN
      OUTCOME MEASURES: Overall, morning, and activity pain, measured on a visual
      analog scale; Maryland Foot Score; walking ability; Short-Form-36 Health Survey
      (SF-36) score; and Problem Elicitation Technique score, measured at 6 and 12
      weeks after treatment completion. RESULTS: At 6 and 12 weeks, there were
      significant improvements in overall pain in both the active group and placebo
      group (mean [SD] improvement, 18.1 [30.6] and 19.8 [33.7] at 6 weeks [P =.74 for
      between-group difference], and 26.3 [34.8] and 25.7 [34.9] at 12 weeks [P =.99],
      respectively). Similar improvements in both groups were also observed for morning
      and activity pain, walking ability, Maryland Foot Score, Problem Elicitation
      Technique, and SF-36. There were no statistically significant differences in the
      degree of improvement between treatment groups for any measured outcomes.
      CONCLUSION: We found no evidence to support a beneficial effect on pain,
      function, and quality of life of ultrasound-guided ESWT over placebo in patients
      with ultrasound-proven plantar fasciitis 6 and 12 weeks following treatment.

PMID- 12234231
TI  - Effectiveness of nurses as providers of birth labor support in North American
      hospitals: a randomized controlled trial.
AB  - CONTEXT: North American cesarean delivery rates have risen dramatically since the
      1960s, without concomitant improvements in perinatal or maternal health. A
      Cochrane Review concluded that continuous caregiver support during labor has many
      benefits, including reduced likelihood of cesarean delivery. OBJECTIVE: To
      evaluate the effectiveness of nurses as providers of labor support in North
      American hospitals. DESIGN: Randomized controlled trial with prognostic
      stratification by center and parity. Women were enrolled during a 2-year period
      (May 1999 to May 2001) and followed up until 6 to 8 postpartum weeks. SETTING:
      Thirteen US and Canadian hospitals with annual cesarean delivery rates of at
      least 15%. PARTICIPANTS: A total of 6915 women who had a live singleton fetus or
      twins, were 34 weeks' gestation or more, and were in established labor at
      randomization. INTERVENTION: Patients were randomly assigned to receive usual
      care (n = 3461) or continuous labor support by a specially trained nurse (n =
      3454) during labor. MAIN OUTCOME MEASURES: The primary outcome measure was
      cesarean delivery rate. Other outcomes included intrapartum events and indicators
      of maternal and neonatal morbidity, both immediately after birth and in the first
      6 to 8 postpartum weeks. RESULTS: Data were received for all 6915 women and their
      infants (n = 6949). The rates of cesarean delivery were almost identical in the 2
      groups (12.5% in the continuous labor support group and 12.6% in the usual care
      group; P =.44). There were no significant differences in other maternal or
      neonatal events during labor, delivery, or the hospital stay. There were no
      significant differences in women's perceived control during childbirth or in
      depression, measured at 6 to 8 postpartum weeks. All comparisons of women's likes
      and dislikes, and their future preference for amount of nursing support, favored
      the continuous labor support group. CONCLUSIONS: In hospitals characterized by
      high rates of routine intrapartum interventions, continuous labor support by
      nurses does not affect the likelihood of cesarean delivery or other medical or
      psychosocial outcomes of labor and birth.

PMID- 12234232
TI  - Inconsistency in evidentiary standards for medical testimony: disorder in the
      courts.
AB  - Several recent decisions by the US Supreme Court have strengthened the ability of
      federal courts to consider medical testimony regarding injuries associated with
      exposure to toxic substances. Judges are expected to examine the basis of all
      expert testimony before it is introduced at trial to ensure that it meets the
      same standards of intellectual rigor that professionals use outside the
      courtroom. However, courts have been inconsistent in measuring this testimony
      against the standards of medical practice, especially when courts consider
      testimony that is not supported by clinical trials or epidemiological studies. A
      number of courts have required standards for expert testimony that exceed those
      that physicians use in ordinary clinical decision making. In this article, we
      illustrate such inconsistencies across federal courts by contrasting different
      decisions in cases involving similar facts and expert testimony. We argue that
      there may be good reason to require a standard of admissibility that exceeds the
      standards of ordinary clinical decision making, but such requirements are not
      faithful to the mandate of the Supreme Court. Courts with especially demanding
      standards are misled if they believe that they are fairly representing medical
      practice. Physicians should respond by correcting courts' misinterpretations of
      medical practice and assisting in the development of legal standards that
      encourage thoughtful and informed consideration of medical testimony by judges
      and juries.

PMID- 12234233
TI  - New evidence for stroke prevention: scientific review.
AB  - CONTEXT: Stroke is a major cause of morbidity and mortality, and the application
      of evidence for stroke prevention varies considerably. OBJECTIVE: To review the
      most recent, high-quality evidence for primary and secondary stroke prevention.
      DATA SOURCES AND STUDY SELECTION: Searches of MEDLINE, The Cochrane Library, and
      the ACP Journal Club were performed to identify English-language articles
      published from 1998 to 2001 that focused on primary and secondary stroke
      prevention. The references of each retrieved article were scanned, and experts in
      the field were contacted to identify additional relevant articles. DATA
      EXTRACTION: Each of the articles was appraised, and its quality was graded with
      levels of evidence based on specific scientific methods that affect a study's
      validity. DATA SYNTHESIS: For primary prevention of stroke, adequate blood
      pressure reduction, and treatment of hyperlipidemia, use of antithrombotic
      therapy in patients with atrial fibrillation and of antiplatelet therapy in
      patients with myocardial infarction are effective and supported by evidence from
      several randomized trials. Effective strategies for the secondary prevention of
      stroke include treatment of hypertension and hyperlipidemia, antithrombotic
      therapy for patients with atrial fibrillation, antiplatelet therapy, and carotid
      endarterectomy in patients with severe carotid artery stenosis. CONCLUSIONS:
      Stroke is a major public health concern, and a significant body of evidence
      supports many primary and secondary prevention strategies.

PMID- 12234234
TI  - New evidence for stroke prevention: clinical applications.
AB  - Stroke is a leading cause of morbidity and mortality in most developed nations.
      There is a significant body of evidence supporting strategies that target primary
      and secondary stroke prevention. This evidence cannot be broadly applied to all
      patients, and each patient's situation and values must be considered with regard
      to shared evidence-based decision making. Several models can be used to apply
      evidence to individual patients, including formal clinical decision analysis,
      decision aids, or simpler tools such as the likelihood of being helped vs harmed.
      Various programmatic models of providing patient care in stroke prevention may
      also be useful; these include specialized clinics or disease-management programs,
      anticoagulation management services, and self-testing and management of
      anticoagulation by patients.

PMID- 12234235
TI  - Predicting gross motor function in cerebral palsy.

PMID- 12234236
TI  - Depression: a call for papers.

PMID- 12234237
TI  - Discontinuation of use and switching of antidepressants: influence of patient
      physician communication.
AB  - CONTEXT: Although current depression treatment guidelines recommend continuing
      antidepressant therapy for at least 4 to 9 months, many patients discontinue
      treatment prematurely, within 3 months. OBJECTIVES: To investigate the
      relationship between patient-physician communication and the continuation of
      treatment with antidepressants and to explore the demographics, adverse effects,
      therapeutic response, and frequency of follow-up visits. DESIGN, SETTING, AND
      PATIENTS: A total of 401 telephone interviews of depressed patients being treated
      with selective serotonin reuptake inhibitor (SSRI) therapy between December 15,
      1999, and May 31, 2000, were conducted and 137 prescribing physicians completed
      written surveys from Northern California Kaiser Permanente health maintenance
      organization outpatient clinics. MAIN OUTCOME MEASURES: Patient-physician
      communication about therapy duration and about adverse effects; therapy
      discontinuation or medication switching within 3 months after start of SSRI
      therapy. RESULTS: Ninety-nine physicians (72%) reported that they usually ask
      patients to continue using antidepressants for at least 6 months, but 137
      patients (34%) reported that their physicians asked them to continue using
      antidepressants for this duration and 228 (56%) reported receiving no
      instructions. Patients who said they were told to take their medication for less
      than 6 months were 3 times more likely to discontinue therapy (odds ratio [OR],
      3.12; 95% confidence interval [CI], 1.21-8.07) compared with patients who said
      they were told to continue therapy longer. Patients who discussed adverse effects
      with their physicians were less likely to discontinue therapy than patients who
      did not discuss them (OR, 0.49; 95% CI, 0.25-0.95). Patients who reported
      discussing adverse effects with their physicians were more likely to switch
      medications (OR, 5.60; 95% CI, 2.31-13.60). Fewer than 3 follow-up visits for
      depression, adverse effects, and lack of therapeutic response to medication were
      also associated with patients' discontinuing therapy. CONCLUSIONS: Discrepancies
      exist between instructions that physicians report they communicate to patients
      and what patients remember being told. Explicit instructions about expected
      duration of therapy and discussions about medication adverse effects throughout
      treatment may reduce discontinuation of SSRI use. Our finding that patients with
      3 or more follow-up visits were more likely to continue using the initially
      prescribed antidepressant medication suggests that frequent patient-physician
      contact may increase the probability that patients will continue therapy.

PMID- 12234243
TI  - Alternatives to animal experiments: producing the fruits.

PMID- 12234244
TI  - The implications of microarray technology for animal use in scientific research.
AB  - Microarray technology has the potential to affect the number of laboratory
      animals used, the severity of animal experiments, and the development of non
      animal alternatives in several areas scientific research. Microarrays can contain
      hundreds or thousands of microscopic spots of DNA, immobilised on a solid
      support, and their use enables global patterns of gene expression to be
      determined in a single experiment. This technology is being used to improve our
      understanding of the operation of biological systems during health and disease,
      and their responses to chemical insults. Although it is impossible to predict
      with certainty any future trends regarding animal use, microarray technology
      might not initially reduce animal use, as is often claimed to be the case. The
      accelerated pace of research as a result of the use of microarrays could increase
      overall animal use in basic and applied biological research, by increasing the
      numbers of interesting genes identified for further analysis, and the number of
      potential targets for drug development. Each new lead will require further
      evaluation i n studies that could involve animals. In toxicity testing,
      microarray studies could lead to increases in animal studies, if further
      confirmatory and other studies are performed. However, before such technology can
      be used more extensively, several technical problems need to be overcome, and the
      relevance of the data to biological processes needs to be assessed. Were
      microarray technology to be used in the manner envisaged by its protagonists,
      there need to be efforts to increase the likelihood that its application will
      create new opportunities for reducing, refining and replacing animal use. This
      comment is a critical assessment of the possible implications of the application
      of microarray technology on animal experimentation in various research areas, and
      makes some recommendations for maximising the application of the Three Rs.

PMID- 12234245
TI  - An assessment of progress in the use of alternatives in toxicity testing since
      the publication of the report of the second FRAME Toxicity Committee (1991).

PMID- 12234246
TI  - Good Cell Culture Practice. ECVAM Good Cell Culture Practice Task Force Report 1.

PMID- 12234247
TI  - In vitro phototoxicity testing: development and validation of a new concentration
      response analysis software and biostatistical analyses related to the use of
      various prediction models.
AB  - As demonstrated in several validation studies, the dermal phototoxic potential of
      chemicals in humans can be effectively assessed by in vitro methods. The core of
      these methods is to monitor dose-response curves of a chemical in the absence and
      presence of light, to quantify the difference between these two curves by
      appropriate measures (either the photo-irritancy factor [PIF], or the mean photo
      effect [MPE]), and to use these measures as predictors of in vivo phototoxicity.
      We present new concentration-response analysis software for in vitro
      phototoxicity testing, which runs on current personal computers, and takes into
      account all the limitations identified when using a former program. We also
      demonstrate the validity and robustness of this new software by applying it
      retrospectively to all data available from two phases of the EU/COLIPA validation
      trial for the 3T3 neutral red update in vitro phototoxicity test. Some frequently
      raised questions pertaining to the use of prediction models in phototoxicity
      testing are addressed, including: the necessity of using prediction models based
      on a cut-off; whether it is justifiable to use sharp prediction cut-off values;
      whether there is a biostatistical justification for the highest concentration of
      the test chemical; and whether repeated testing of a chemical is required.

PMID- 12234248
TI  - A method for the in vitro exposure of human cells to environmental and complex
      gaseous mixtures: application to various types of atmosphere.
AB  - The application of in vitro methods to the analysis of the effects of airborne
      materials is still limited, because there are no generally accepted concepts and
      technologies for efficiently exposing adherent growing cells to test atmospheres,
      especially those comprising complex mixtures of gaseous and particulate phases.
      The introduction of in vitro research into the field of inhalation toxicology
      offers a unique possibility for using human cells and tissues for pre-screening
      studies, thus reducing the necessity for animal experiments, and cutting the
      numbers of animals used in toxicological testing. We therefore developed a novel
      experimental concept that uses an exposure device based on the cell cultivation
      system CULTEX (Patent No. DE 198011763; PCT/EP99/00295). This allowed us to
      investigate environmental atmospheres, which were chemically and physically
      unmodified, in an in vitro system, by exposing the target cells directly at the
      air/liquid interface. The exposure device itself is small and flexible enough to
      be connected to a variety of aerosol-generating systems without the need for an
      incubator, as it fulfils all the requirements for maintaining cell viability over
      a defined period. The general applicability and the sensitivity of this in vitro
      approach for testing various generated atmospheres under the same cell-exposure
      conditions were demonstrated by studying dose-dependent cytotoxic effects in
      human lung epithelial cells exposed to air contaminated with single gases or
      complex mixtures, such as diesel exhaust fumes and side-stream cigarette smoke.

PMID- 12234249
TI  - Stable biocompatible adjuvants--a new type of adjuvant based on solid lipid
      nanoparticles: a study on cytotoxicity, compatibility and efficacy in chicken.
AB  - A new type of adjuvant was tested for its ability to initiate antibody production
      in chickens, and its cellular and tissue compatibility were assessed. The stable
      biocompatible adjuvants tested are based on surface-modified solid lipid
      nanoparticles (SLNs), made from paraffin or biodegradable glycerides, and are
      simply admixed to the antigens before administration. The tissue-damaging potency
      of four formulations of the new adjuvants (H1, H2, H3 and H4) were first tested
      in vitro by using human foreskin fibroblasts and RAW 264.7 macrophages. The
      adjuvants were well tolerated by both cell types. Immunisation studies in
      chickens were performed by using a Mycoplasma bovis antigen and mouse
      immunoglobulin G (IgG). The resulting antibodies were non-invasively extracted
      from egg yolk. The use of the various adjuvant formulations resulted in a
      significant production of specific antibodies after the first and second booster
      immunisations. Freund's complete adjuvant (FCA), considered until now to be the
      "gold standard" among the adjuvants, revealed the highest antibody titre against
      mouse IgG. SLNs with a particle size of more than 100 nm exhibited a clear
      adjuvant activity, whereas SLNs with a particle size below 100 nm, in various
      concentrations, revealed a lower adjuvant activity. Immunisation of chickens with
      the mouse IgG alone, dissolved in phosphate-buffered saline, resulted in a slow
      antibody titre development. At the end of the experiment, the chickens were
      examined for vaccination-associated tissue damage. In contrast to FCA, the SLN
      formulations caused only minor tissue irritation at the injection sites. In
      conclusion, SLNs seem to be a promising alternative to FCA for antibody
      production in chickens, and potentially in other animals.

PMID- 12234250
TI  - Ionizing radiation induces ataxia telangiectasia mutated kinase (ATM)-mediated
      phosphorylation of LKB1/STK11 at Thr-366.
AB  - The serine/threonine protein kinase LKB1 functions as a tumour suppressor, and
      mutations in this enzyme lead to the inherited Peutz-Jeghers cancer syndrome. We
      previously found that LKB1 was phosphorylated at Thr-366 in vivo, a residue
      conserved in mammalian, Xenopus and Drosophila LKB1, located on a C-terminal non
      catalytic moiety of the enzyme. Mutation of Thr-366 to Ala or Asp partially
      inhibited the ability of LKB1 to suppress growth of G361 melanoma cells, but did
      not affect LKB1 activity in vitro or LKB1 localization in vivo. As a first step
      in exploring the role of this phosphorylation further, we have generated a
      phosphospecific antibody specifically recognizing LKB1 phosphorylated at Thr-366
      and demonstrate that exposure of cells to ionizing radiation (IR) induced a
      marked phosphorylation of LKB1 at Thr-366 in the nucleus. Thr-366 lies in an
      optimal phosphorylation motif for the phosphoinositide 3-kinase-like kinases DNA
      dependent protein kinase (DNA-PK), ataxia telangiectasia mutated kinase (ATM) and
      ataxia telangiectasia-related kinase (ATR), which function as sensors for DNA
      damage in cells and mediate cellular responses to DNA damage. We demonstrate that
      both DNA-PK and ATM efficiently phosphorylate LKB1 at Thr-366 in vitro and
      provide evidence that ATM mediates this phosphorylation in vivo. This is based on
      the finding that LKB1 is not phosphorylated in a cell line lacking ATM in
      response to IR, and that agents which induce cellular responses via ATR in
      preference to ATM poorly induce phosphorylation of LKB1 at Thr-366. These
      observations provide the first link between ATM and LKB1 and suggest that ATM
      could regulate LKB1.

PMID- 12234251
TI  - Structural elucidation of zwitterionic carbohydrates derived from
      glycosphingolipids of the porcine parasitic nematode Ascaris suum.
AB  - Carbohydrates substituted with phosphocholine (PC) and phosphoethanolamine (PE)
      were released from zwitterionic glycosphingolipids of the pig parasitic nematode
      Ascaris suum by treatment with endoglycoceramidase. Individual glycans were
      obtained by HPLC on porous graphitic carbon followed by high-pH anion-exchange
      chromatography. In addition to the known pentasaccharides Gal alpha 3GalNAc beta
      4[PC6]GlcNAc beta 3Man beta 4Glc and Gal alpha 3GalNAc beta 4[PC6]GlcNAc beta
      3[PE6]Man beta 4Glc, the corresponding tri- and tetra-saccharides, as well as
      components with elongated structures, could be identified by matrix-assisted
      laser-desorption ionization-time-of-flight MS, methylation analysis, 1H- and 13C
      NMR spectroscopy, exoglycosidase cleavage and electrospray ionization ion-trap
      MS. The extended components comprised novel structural motifs such as di
      substituted alpha-galactose carrying two beta-linked galactosyl residues, which
      were found to bear, in part, further fucose, galactose, N -acetylgalactosamine
      and/or N -acetylglucosamine moieties. Furthermore, additional fucosylation of the
      PC-substituted N -acetylglucosamine and a non-terminal fucosyl motif were
      detected. In conclusion, this study contributes significant new information on
      the glycome of nematodes.

PMID- 12234252
TI  - alpha1B-Adrenergic receptor phosphorylation and desensitization induced by
      transforming growth factor-beta.
AB  - Transforming growth factor-beta (TGF-beta) induced alpha(1B)-adrenergic receptor
      phosphorylation in Rat-1 fibroblasts stably expressing these adrenoceptors. This
      effect of TGF-beta was rapid, reaching a maximum within 30 min and decreasing
      thereafter, and concentration-dependent (EC(50) 0.3 pM). The phosphoinositide 3
      kinase inhibitors wortmannin and LY294002, and the protein kinase C inhibitors
      staurosporine, Ro 318220 and bisindolylmaleimide, blocked the effect of this
      growth factor. alpha(1B)-Adrenergic receptor phosphorylation was associated with
      desensitization, as indicated by a reduction in the adrenergic-mediated
      production of [(3)H]inositol phosphates. Phosphorylation of alpha(1B)-adrenergic
      receptors by TGF-beta was also observed in Cos-1 cells transfected with the
      receptor. Co-transfection of the dominant-negative mutant of the regulatory
      subunit of phosphoinositide 3-kinase (Deltap85) inhibited the phosphorylation of
      alpha(1B)-adrenergic receptors induced by TGF-beta. Our results indicate that
      activation of TGF-beta receptors induces alpha(1B)-adrenergic receptor
      phosphorylation and desensitization. The data suggest that phosphoinositide 3
      kinase and protein kinase C play key roles in this effect of TGF-beta.

PMID- 12234253
TI  - Cloning and functional characterization of the human fractalkine receptor
      promoter regions.
AB  - We have previously shown that reduced expression of the fractalkine receptor,
      CX3CR1, is correlated with rapid HIV disease progression and with reduced
      susceptibility to acute coronary events. In order to elucidate the mechanisms
      underlying transcriptional regulation of CX3CR1 expression, we structurally and
      functionally characterized the CX3CR1 gene. It consists of four exons and three
      introns spanning over 18 kb. Three transcripts are produced by splicing the three
      untranslated exons with exon 4, which contains the complete open reading frame.
      The transcript predominantly found in leucocytes corresponds to the splicing of
      exon 2 with exon 4. Transcripts corresponding to splicing of exons 1 and 4 are
      less abundant in leucocytes and splicing of exons 3 and 4 are rare longer
      transcripts. A constitutive promoter activity was found in the regions extending
      upstream from untranslated exons 1 and 2. Interestingly, exons 1 and 2 enhanced
      the activity of their respective promoters in a cell-specific manner. These data
      show that the CX3CR1 gene is controlled by three distinct promoter regions, which
      are regulated by their respective untranslated exons and that lead to the
      transcription of three mature messengers. This highly complex regulation may
      allow versatile and precise expression of CX3CR1 in various cell types.

PMID- 12234254
TI  - Malaria vaccine: candidate antigens, mechanisms, constraints and prospects.
AB  - More than 30 years after the first report of successful vaccination against
      malaria using radiation-attenuated sporozoites, an effective malaria vaccine is
      not yet available. However, field and experimental data indicate that it can be
      developed. An astonishing amount of data has accumulated concerning parasite
      biology, host-parasite interactions, immunity and escape mechanisms, targets and
      modulators of immune responses. Nevertheless, so far this knowledge has not been
      enough to make us understand how to properly manipulate the whole system to build
      an effective vaccine. In this article, we describe candidate antigens,
      mechanisms, targets and trials performed with potential malaria vaccines and
      discuss the approaches, in vivo and in vitro models, constraints and how
      technologies such as DNA vaccination, genomics/proteomics and reverse
      immunogenetics are providing exciting results and opening new doors to make
      malaria vaccine a reality.

PMID- 12234255
TI  - Linkage relationships of genes coding for alpha2-macroglobulin, C3 and C4 in the
      zebrafish: implications for the evolution of the complement and Mhc systems.
AB  - The alpha2-macroglobulin (A2M) and the complement components C3 and C4 are
      related proteins derived from a common ancestor. Theoretically, this derivation
      could have occurred either by tandem duplications of their encoding genes or by
      polyploidization involving chromosomal segments, a chromosome or the whole
      genome. In tetrapods the A2M-, C3- and C4-encoding genes are generally each
      located on a different chromosome. This observation has been interpreted as
      supporting their origin by polyploidization. We identified and mapped (with the
      help of a radiation hybrid panel of cell lines) the A2M, C3 and C4 loci in the
      zebrafish, Danio rerio. Each of the three types of loci is present in the
      zebrafish in multiple copies, but all of the identified copies of a given type
      map to the same region in linkage groups 1 (C3) and 15 (A2M, C4). The A2M and C4
      loci are mapped in the same region not linked to any of the class I or class II
      major histocompatibility complex (Mhc) loci. These observations are interpreted
      as supporting the origin of the A2M family of genes by tandem duplications,
      followed by the dispersal of the copies to different chromosomes. It is also
      argued that the association of C4 with the class I/II loci in tetrapods is
      accidental and without functional significance.

PMID- 12234256
TI  - Cyclosporin-A differentially affects apoptosis during in vivo rat thymocyte
      maturation.
AB  - Maturation arrest and interference with selection are two well-documented effects
      of cyclosporin-A (CsA) on the thymus. We recently hypothesized that these effects
      are related and owing to the reduced T-cell receptor (TCR)-CD3 complex-mediated
      signal transduction in thymocytes upon CsA treatment. In this hypothesis, the
      maturation arrest is the result of the additional depletion of thymocytes that
      normally survive by positive selection, whereas the impaired self-tolerance
      induction is caused by an increased survival of thymocytes that normally undergo
      negative selection. In this view, it is anticipated that CsA differentially
      affects thymocyte apoptosis during in vivo thymocyte maturation. Indeed, we
      report in this study a strong increase in apoptotic cells in the thymic cortex on
      in situ analysis. Simultaneously, the number of apoptotic cells had decreased at
      the cortico-medullary zone which is held to be the site for negative selection.
      Rapamycin (Rapa) also interferes with thymocyte maturation by inhibiting cytokine
      driven proliferation. Hence, Rapa preferentially affects the early maturational
      stages of thymocyte development and is considered not to alter thymocyte
      selection and subsequent apoptotic events. Indeed, the number of apoptotic events
      appears not to be altered. However, possibly owing to the decrease in cortical
      macrophages, the apoptotic cells revealed an atypical enumeration around blood
      vessels. Taken together, our results favour the hypothesis that the dominant
      effect of CsA on the thymus is the reduction of the TCR-CD3 complex-mediated
      signal transduction in thymocytes upon interaction with stromal cells.
      Furthermore, the preferential localization of apoptotic cells next to blood
      vessels upon Rapa administration may indicate that endothelial cells are a back
      up system for the removal of apoptotic cells.

PMID- 12234257
TI  - An experimental vaccine expressing wild-type p53 induces protective immunity
      against glioblastoma cells with high levels of endogenous p53.
AB  - Inoculation of mice with a recombinant vaccinia virus expressing the full-length
      mouse wild-type p53 protein (Vp53-wt) was shown to induce partial protection
      against peripheral challenge with a mouse glioblastoma cell line, termed GL261,
      expressing high levels of nuclear, endogenous wild-type p53. In vivo experiments
      with knockout (KO) mice and mice treated with depleting doses of antibodies
      specific to lymphocyte subsets revealed that vaccine efficacy depended on CD4+
      and CD8+ T cells as well as on natural killer (NK) cells. Vp53-wt virus
      vaccinated mice that failed to develop tumours upon challenge with a minimal
      tumourigenic dose of GL261 cells remained completely resistant to further
      challenge with increased doses of GL261 cells. The efficacy of the Vp53-wt
      vaccine was improved by adding recombinant mouse interleukin-12 (rIL-12) as an
      adjuvant at the time of tumour challenge. The induction of T cells to p53 in Vp53
      wt virus-immune mice was also demonstrated at the tumour site by immunochemistry
      and was further confirmed by a delayed-type hypersensitivity response to the p53
      protein, although in vitro experiments using splenocytes from vaccinated mice
      failed to demonstrate CD4+ or CD8+ T-cell activity to p53.

PMID- 12234258
TI  - Establishment of animal model of antigen-specific T lymphocyte recruitment into
      nasal mucosa.
AB  - DO11.10 transgenic mice, expressing an ovalbumin (OVA)-specific alphabeta T-cell
      receptor (TCR), have been used as a model of various immune diseases associated
      with T lymphocytes. Some studies of immunoresponse in lung have involved adoptive
      transfer of DO11.10 mice. As of yet, however, there have been no studies of the
      adoptive transfer model in the upper airway. The purpose of this study was to
      establish an animal model to clarify the recruitment mechanism and the roles of
      Th2 cells in allergic rhinitis. In accordance with the adoptive transfer system,
      we generated Th0, Th1 and Th2 cells from DO11.10 mice and transferred them into
      wild type BALB/c mice. Following nasal OVA challenge to DO11.10 mice or to the
      BALB/c mice into which antigen-specific Th2 cells had been transferred, the
      number of local antigen-specific TCR-positive cells accompanying the local
      eosinophilia had significantly increased. However, nasal OVA challenge to BALB/c
      mice into which antigen-specific Th0 or Th1 cells were transferred failed to
      increase the number of local OVA-specific TCR positive cells. These observations
      suggest that an antigen-specific homing mechanism of Th2 cells may exist in nasal
      mucosa. Analysis of this model will assist in the development of new therapeutic
      strategy, which targets Th2 cells in allergic rhinitis.

PMID- 12234259
TI  - Increased Bcl-2 and reduced Bax expression in infected macrophages in slowly
      progressive primary murine Mycobacterium tuberculosis infection.
AB  - Mycobacterium tuberculosis (MTB) persists in host macrophages (Mphis) because it
      has developed mechanisms to escape Mphi killing. In vitro studies have shown that
      MTB can induce and inhibit apoptosis by causing the expression of Bax and Bcl-2,
      respectively, suggesting that the infected cells' fate depends on pro- and
      antiapoptotic signals. In the present study, we investigated the role of Bcl-2 in
      MTB infection in situ. The aim was to study the pattern and distribution of Bcl-2
      and Bax in cellular infiltrates of MTB-infected B6D2F1 hybrid mice and correlate
      the expression with the presence of MTB antigens (MAgs). Using formalin-fixed
      lung tissues (n = 45), our results showed a significant difference in the
      percentage of Mphis stained for Bcl-2 or MAgs and Bax (P < 0.0001). Bcl-2
      expression was increased in a population of Mphis and corresponded in intensity,
      colocalization and percentage with that of MAgs on the same cells, while Bax
      expression was reduced. In lymphocyte aggregates, Bcl-2 and Bax did not show any
      differences. We conclude that overexpression of Bcl-2 in Mphis containing MTB may
      be associated with intracellular survival of the bacilli, thus demonstrating one
      way by which MTB can escape the host's cellular response and killing.

PMID- 12234260
TI  - Histoplasma capsulatum inhibits apoptosis and Mac-1 expression in leucocytes.
AB  - Histoplasma capsulatum is a fungus found intracellularly in neutrophils and
      peripheral blood mononuclear cells (PBMCs), suggesting that it is capable of
      evading damage and survives inside these cells. In this study, we report that
      neutrophils from H. capsulatum-infected mice, and human neutrophils and
      mononuclear cells exposed to H. capsulatum presented less apoptosis than those
      from noninfected animals or cells exposed to medium only. Moreover, cells
      harvested from infected animals are resistant to apoptosis induced by
      dexamethasone - a proapoptotic stimulant. We also show that neutrophils harvested
      from infected mice and PBMCs from humans exposed to the fungus had a greatly
      decreased Mac-1 expression. We conclude that H. capsulatum induces an
      antiapoptotic state on leucocytes, which correlates with decreased cell-surface
      Mac-1 expression. These facts may represent an escape mechanism for the fungus by
      delaying cell death and allowing the fungus to survive inside leucocytes.

PMID- 12234262
TI  - Influence of the polyclonal activation induced by Plasmodium chabaudi on ongoing
      OVA-specific B- and T-cell responses.
AB  - Infection by Plasmodium chabaudi results in polyclonal activation, massive
      proliferation and differentiation of lymphocytes with parasite-unrelated
      specificities. To verify if polyclonal activation includes experienced B and T
      lymphocytes and if it modifies pre-established cytokine and Ig-isotype patterns,
      mice were immunized with ovalbumin (OVA) in alum, a condition that favours T
      helper 2/immunoglobulin G1 (Th2/IgG1) responses, and infected with P. chabaudi 7
      or 80 days later. Polyclonal activation markedly increased the number of anti-OVA
      Ig-secreting cells in the spleen, an effect more patent in mice infected 7 days
      after OVA immunization, but also evident in mice infected after 80 days. The Ig
      isotype profile predefined by immunization was not qualitatively modified by
      polyclonal activation. Thus, although P. chabaudi infection preferentially
      induces IgG2a, the expanded anti-OVA response is dominated by IgG1. Polyclonal
      expansion of the anti-OVA response did not yield an enlarged memory B-cell pool
      that could be recalled months later by OVA boosting. Moreover, polyclonal
      activation of anti-OVA IgG1-secreting cells did not increase this antibody in
      serum, a probable consequence of the high Ig turnover observed during infection.
      When OVA-specific T-cell cytokines were evaluated, we observed an increase of
      both interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) in mice infected 7
      days after immunization, whereas in those infected after 80 days, only IL-4 was
      augmented. These results suggest that polyclonal activation expands experienced B
      and T-cell compartments, preserving their antibody and cytokine patterns.

PMID- 12234261
TI  - Selective small antigenic structures are capable of inducing widespread
      autoimmunity which closely mimics the humoral fine specificity of human SLE.
AB  - Recent data have suggested that autoantibodies in lupus can progress from simple
      immunity against a few antigenic structures to a complex response against
      multiple autoantigens. Our aim was to determine whether these diverse epitope
      patterns can indeed be generated by antigenic challenge with a single, small
      structure. Rabbits were immunized with either a 60 kDa Ro peptide commonly
      antigenic in human systemic lupus erythematosus (SLE) (Ro 274-289) or one which
      is rarely a humoral target (Ro 500-515). Rabbits immunized with the antigenic
      peptide (Ro 274-289) not only developed antibodies to multiple epitopes of 60 kDa
      Ro and La, as has been described, but also produced non-cross-reactive antibodies
      to the common spliceosomal proteins Sm B' and D1, and nRNP A and C. Rabbits
      immunized with the Ro 274-289 peptide also mount a progressive, diversified
      immune response to the sequential antigenic regions of these proteins (60 kDa Ro,
      Sm B' and D1, nRNP A and C), which is nearly identical to that seen in human SLE.
      Animals immunized with the nonantigenic peptide Ro 500-515 develop antibodies
      only to 60 kDa Ro. These results demonstrate that loss of tolerance to select
      single, small antigenic structures can begin a cascade which virtually recreates,
      at the epitope level, the humoral autoimmune specificity seen in human SLE.

PMID- 12234263
TI  - Bcl-2-mediated regulation of CD69-induced apoptosis of human eosinophils:
      identification and characterization of a novel receptor-induced mechanism and
      relationship to CD95-transduced signalling.
AB  - Elimination of the eosinophils from the airways by selective induction of
      apoptosis represents a therapeutic approach for asthma. Here we report on a
      possible target molecule, the surface receptor CD69. To simulate an asthmatic
      response, segmental allergen challenge in mild asthmatics was performed.
      Eosinophil numbers increased in bronchoalveolar lavage (BAL) at 18 h. In contrast
      to blood cells, BAL eosinophils expressed the activation marker CD69. Purified
      blood eosinophils stimulated with granulocyte/macrophage colony-stimulating
      factor (GM-CSF) or interferon-gamma (IFN-gamma) expressed CD69 and showed
      prolonged viability. Only IFN-gamma enhanced constitutive CD95 expression.
      Coincubation with anti-CD69 or anti-CD95 monoclonal antibody (MoAb) induced
      apoptosis, as revealed by propidium iodide incorporation, membrane blebbing and
      nuclear fragmentation. Additionally, both anti-CD69 and anti-CD95 MoAb reduced
      cytokine-enhanced Bcl-2 expression. In conclusion, CD69 transduces a Bcl-2
      dependent death signal when ligated by a specific antibody. As, in contrast to
      the ubiquitous death-inducer CD95, the function of CD69 appears to be restricted
      to activated eosinophils, it represents an ideal target for therapeutic
      intervention in asthma.

PMID- 12234264
TI  - Successful generation of sperm protein 17 (Sp17)-specific cytotoxic T lymphocytes
      from normal donors: implication for tumour-specific adoptive immunotherapy
      following allogeneic stem cell transplantation for Sp17-positive multiple
      myeloma.
AB  - Sperm protein 17 (Sp17) is a highly immunogenic cancer-testis antigen expressed
      by tumour cells from up to 30% of patients with multiple myeloma (MM). We
      recently successfully generated Sp17-specific human leucocyte antigen (HLA)-A1
      and B27-restricted cytotoxic T lymphocytes (CTLs) from the peripheral blood of a
      healthy donor. Because CTLs were able to kill HLA-matched fresh myeloma cells, it
      may be possible to generate and administer myeloma-specific donor T cells to MM
      patients following allogeneic stem cell transplantation to enhance graft-versus
      myeloma (GVM) without inducing graft-versus-host disease (GVHD). To determine how
      widely applicable this approach is, we have determined the ability to generate
      Sp17-specific CTLs from four consecutive healthy donors with other HLA class I
      phenotypes. We found that Sp17-specific HLA class I-restricted CTLs could be
      easily generated from all four donors. Sp17-specific CTLs were primarily CD8 in
      phenotype and produced interferon-gamma and very little interleukin-4. These T
      cells killed target cells primarily via the perforin-mediated route. These
      results therefore suggest that myeloma-specific donor T-cell infusion that
      targets Sp17 to selectively enhance GVM could be applicable to patients with
      Sp17+ MM.

PMID- 12234265
TI  - Should physical activity and/or competitive sports be curtailed in pediatric
      heart transplant recipients?

PMID- 12234266
TI  - The history of pediatric heart and lung transplantation.
AB  - As is the case with other forms of solid organ transplantation, success with
      heart and lung transplantation in the pediatric population was a natural
      extension of success with these procedures in adults. As a result, to review the
      history of pediatric heart and lung transplantation, one must by necessity review
      the landmarks in research and the events that gave way to successful heart and
      lung transplantation in adults.

PMID- 12234267
TI  - Epstein-Barr virus-related lymphoproliferation in children after liver
      transplant: role of immunity, diagnosis, and management.
AB  - Tumor occurrence following immunosuppression remains a major concern in children
      after liver transplantation. More than 50% of these tumors belong to the post
      transplant lymphoproliferative diseases (PTLD) and are diagnosed during
      childhood. These PTLD are mostly related to primary Epstein-Barr virus (EBV)
      infection and a heavy immunosuppressive regimen. Improvement in their prognosis
      was reached thanks to a better knowledge of their pathogenesis, risk factors and
      clinical presentation, linked probably to earlier management. However, their
      incidence remains stable (occurring in 5-15% of children after liver
      transplantation) despite different pre-emptive strategies based on these
      parameters. Moreover, acute graft rejection and subsequent risk of graft loss is
      a common side-effect of PTLD treatment. EBV viral load determination by
      quantitative polymerase chain reaction (PCR) is so far the only predictive marker
      proposed for PTLD prevention and PTLD treatment monitoring, although limited by a
      lack of specificity. New immunologic techniques have allowed the demonstration of
      a defect of the EBV-specific cellular immunity in the patients with PTLD. The
      level of immunity is correlated to the viral load and improves during recovery
      from PTLD. These recent findings add further knowledge to PTLD pathogenesis and
      management.

PMID- 12234268
TI  - Stimulated cortisol secretion is not correlated with prednisone dose or with
      steroid side-effects in children after renal transplantation.
AB  - Impairment of adrenocortical function and other adverse effects have to be
      considered whenever corticosteroids are applied for a prolonged period of time.
      We hypothesized that the assessment of adrenal function with adrenocortiocotropin
      (ACTH) stimulation reflects the sensitivity to corticosteroids and would predict
      the development of side-effects in pediatric patients on triple immunosuppression
      after renal transplantation.

PMID- 12234269
TI  - Long-term survival after liver transplantation in children with metabolic
      disorders.
AB  - BACKGROUND: Liver transplantation for inherited metabolic disorders aims to save
      the patient's life when the disorder is expected to progress to organ failure,
      and to cure the underlying metabolic defect. METHODS: We retrospectively analyzed
      146 pediatric liver transplants (28 metabolic; 118 non-metabolic) performed
      between 1986 and 2000. RESULTS: Twenty-eight transplants were performed in 24
      children with metabolic disease (8 females; 16 males; age range 3 months to 17
      yr). Indications included alpha-1-antitrypsin deficiency (n = 8), two cases each
      of hyperoxaluria type 1, Wilson's disease, hereditary tyrosinemia type I,
      citrullinemia, methylmalonic acidemia, and one case each of propionic acidemia,
      Crigler-Najjar syndrome type I, neonatal hemachromatosis, hemophilia B, Niemann
      Pick disease type B, and cystic fibrosis. Eighteen transplants were whole organ
      grafts and 10 were lobar or segmental. Auxiliary liver transplants were performed
      in two patients and three received combined liver-kidney transplants. There were
      three deaths from sepsis, two from chronic rejection, and one from fulminant
      hepatitis. Seven of 10 patients currently of school age are within 1 yr of
      expected grade and three who had pretransplant developmental delay have remained
      in special education. Actuarial survival rates at 5 and 10 yr are 78% and 68%,
      respectively, with mean follow-up in excess of 5 yr. These results compare
      favorably to 100 pediatric patients transplanted for non-metabolic etiologies
      (65% and 61%, respectively) (p= NS). CONCLUSIONS: Pediatric liver transplantation
      for metabolic disorders results in excellent clinical and biochemical outcome
      with long survival and excellent quality of life for most recipients.

PMID- 12234270
TI  - Allograft rejection in pediatric liver transplantation: Comparison between
      cadaveric and living related donors.
AB  - The aim of this study was to determine whether living related liver
      transplantation has an immunological advantage compared with cadaveric liver
      transplants in children. The records of 100 pediatric primary liver transplant
      recipients performed between January 1992 and December 1998 at the University of
      California, San Francisco Medical Center, were reviewed retrospectively. Ten
      children who died or required a second graft within the first 14 post-operative
      days were excluded from this study group. Two children with combined kidney-liver
      transplants were also excluded. As a result, the study group included 51 children
      in the cadaveric liver transplantation (CLT) group and 37 children in the living
      related liver transplantation (LRLT) group. Until 1995, primary immunosuppression
      consisted of cyclosporin A, azathioprine and steroids. Since 1995, primary
      immunosuppression consisted of cyclosporin A, mycophenolate mofetil and steroids.
      Actuarial graft survival rates at 1, 2 and 5 yrs were 90%, 80.9% and 80.9% in the
      CLT group vs. 94.6%, 91.6% and 78.5% in the LRLT group, respectively (NS).
      Rejection was diagnosed in 40 of 51 cadaveric first grafts (78.4%) and 25 of 37
      living-related primary grafts (67.6%). Rejection episodes were diagnosed greater
      than 1 yr post-transplantation in 11 of 51 cadaveric first grafts (21.6%) and
      none of 37 living-related primary grafts (0%) (p < 0.05). LRLT succeeded in
      reducing the immunosuppressive therapy compared with CLT at 24 months after
      transplantation (p < 0.05). The overall incidence of rejection and graft survival
      rate were comparable in CLT and LRLT; however, rejection episodes in LRLT
      recipients diagnosed greater than 1 yr post-transplant were significantly fewer
      than CLT recipients. LRLT have a partial immunological advantage compared with
      CLT.

PMID- 12234271
TI  - Transient hyperphosphatasemia after organ transplantation in children.
AB  - Transient, isolated hyperphosphatasemia is a rare, benign condition of childhood.
      Few cases have been described in transplant patients. We report six cases: three
      after liver transplantation and three after kidney transplantation. Such a
      phenomenon was found to be as benign after organ transplantation as it is in
      healthy children. Hence, an isolated increase in the serum alkaline phosphatase
      level following transplantation should not be of concern in this population of
      patients.

PMID- 12234272
TI  - A strategy to calculate cyclosporin A area under the time-concentration curve in
      pediatric renal transplantation.
AB  - The complete area under the time-concentration curve (AUC) is considered the gold
      standard for cyclosporin A (CsA) monitoring, particularly in pediatric kidney
      graft recipients who have great absorption and drug clearance variability.
      However, complete AUC is time-consuming and expensive. For this reason, we
      retrospectively reviewed 131 complete 4-h AUC (AUC0-4) performed in 34 children
      (mean age 10.6 +/- 2 yr) in order to construct an equation to calculate AUC0-4.
      The median time after transplantation was 540 (range: 247-1,358) days. Multiple
      regression analysis was performed either with a single variable or with a
      combination of two variables. CsA blood concentration at the second hour after
      the oral morning dose (C2) was the best predictor of AUC0-4, where AUC0-4 = 424 +
      (2.65 x C2), R2 = 0.81, p < 0.001. Only the combination of C1 and C2 offered
      mathematical improvement over the C2 equation. The same analysis was made for
      pharmacokinetic curves performed earlier than 6 months (79 +/- 55 days, range 8
      169 days) and after 1 yr of transplantation. In both time-periods, C2 was the
      best parameter to use to calculate AUC0-4. The equations obtained during these
      two time-periods were very close to the one for the whole population. Our data
      shows that C2 can be safely used to estimate AUC0-4. However, for values above
      4,000 ng/h/mL, the formula overestimates the trapezoidal AUC0-4. The C2 equation
      simplifies the CsA monitoring as a result of its high predictive value and
      clinical feasibility.

PMID- 12234273
TI  - Hematopoietic and immune recovery after allogeneic peripheral blood stem cell
      transplantation and bone marrow transplantation in a pediatric population.
AB  - To compare the hematopoietic and immune recoveries after allogeneic
      transplantation with different cell sources, we analyzed the recovery patterns of
      blood components after allogeneic peripheral blood stem cell transplantation
      (PBSCT) in comparison with that after allogeneic bone marrow transplantation
      (BMT) in a pediatric population. Sixteen patients received PBSCT, and 24 received
      BMT between January, 1995 and March, 2000. The patients had acute lymphoblastic
      leukemia (ALL; n = 22), acute myelogenous leukemia (AML; n = 8), myelodysplastic
      syndrome (MDS; n = 3), or other diseases (n = 7). The median ages of patients in
      the PBSCT and BMT groups were 9 yr and 6 yr, respectively. Cyclosporin A (CsA)
      plus methotrexate or methylprednisolone was used as a graft-vs.-host disease
      (GvHD) prophylaxis regimen in the PBSCT group, whereas CsA alone or methotrexate
      alone was used in the BMT group. Circulating lymphocyte numbers and
      subpopulations determined by flow cytometric analysis were used as markers of
      immune recovery. In the PBSCT group, the median number of harvested CD34+ cells
      was 7.25 (range: 1.3-27.6) x 106/kg of the recipient's body weight, while the
      median number of harvested nucleated cells was 4.7 (range: 3.7-10.5) x 108/kg.
      All of the patients were engrafted. Myeloid engraftment occurred sooner after
      PBSCT than after BMT (median number of days to achieve absolute neutrophil counts
      (ANC) > 0.5 x 109/L; 11 and 15, respectively; p < 0.0001) and similar results
      were found for platelet engraftment (median number of days to achieve a platelet
      count of > 20 x 109/L; 12 and 21, respectively; p = 0.004). On the other hand,
      after PBSCT the absolute numbers of total circulating lymphocytes and lymphocyte
      subpopulations were not significantly different from those after BMT. The
      incidence of acute GvHD after PBSCT was the same as that after BMT, while chronic
      GvHD developed more frequently after PBSCT than after BMT (p = 0.005). In a
      pediatric population, the indications for PBSCT and BMT should be based on these
      findings in addition to regard for the donor's safety.

PMID- 12234274
TI  - Cat scratch disease and acute rejection after pediatric renal transplantation.
AB  - Cat scratch disease (CSD) can lead to unexplained fever, generalized
      lymphadenopathy and organomegaly in immunocompetent individuals. CSD has rarely
      been reported in immunocompromised transplant recipients, where its clinical
      features would mimic the more common post-transplant lymphoproliferative disease
      (PTLD). We report three cases of CSD seen recently in children who had received
      prior kidney transplants. The three children were between 7 and 9 yr old, and had
      received kidney transplants 2-4 yr prior, with stable renal function. In each
      case, there was unexplained fever with either lymphadenopathy or organomegaly.
      The diagnosis of CSD was suggested by a history of new cats being introduced into
      each household and confirmed in all cases by the serological presence of a
      significant titer (> 1 : 64) of IgM antibodies to Bartonella henselae. Tests for
      other bacterial infections, cytomegalovirus and Epstein-Barr virus infections
      were negative. All the patients showed a clinical improvement with anti-microbial
      therapy. In patients A and B, the CSD was associated with an acute rejection
      episode shortly after diagnosis. The rejection episodes were reversed by
      intravenous steroid pulse therapy. Only four cases of CSD have been previously
      reported following solid organ transplantation. Acute rejection following CSD has
      not been previously reported. CSD should be included in the differential
      diagnosis of fever in the post-transplant setting, especially where PTLD is
      suspected.

PMID- 12234275
TI  - Repeated detection of gas in the portal vein after liver transplantation: A sign
      of EBV-associated post-transplant lymphoproliferation?
AB  - A 1-yr-old child presented with intractable right sided pleural effusion and
      progressive clinical deterioration 3 weeks after liver transplantation for
      Alagille Syndrome. He had been treated successfully for severe acute rejection
      before. Ultrasound and Doppler mode studies repeatedly demonstrated air in the
      portal vein. Intra-abdominal and intra-thoracic lymphoproliferation was detected,
      and EBV virus load and serology were suggestive of primary EBV infection. Liver
      biopsy revealed blast-like infiltrates of B-cells, considered diagnostic for post
      transplant lymphoproliferative disease. The disease resolved upon reduction of
      immunosuppression. We suggest that the detection of portal vein gas in pediatric
      liver transplant recipients beyond the early post-operative period may be a sign
      of intra-abdominal post-transplant lymphoproliferative disease.

PMID- 12234276
TI  - Drug-induced lupus as a cause of relapsing inflammatory disease after renal
      transplantation.
AB  - We discuss the case of an 18-year-old-boy presenting with relapsing fever,
      arthralgia, myalgia and renal failure, 7 yr after renal transplantation. A
      thorough diagnostic work-up for infectious and inflammatory diseases revealed a
      mastoiditis and atypical mycobacteria, but symptoms persisted after treatment.
      Persistent antinuclear antibodies in combination with cardiolipin and
      myeloperoxidase antibodies, despite negative dsDNA antibodies, suggested a drug
      induced lupus-like syndrome. Six months after withdrawal of dihydralazine, all
      symptoms had disappeared. Drug-induced lupus should be considered as an important
      differential diagnosis in transplanted patients with recurrent inflammatory
      disease in conjunction with lupus-like symptoms and negative dsDNA antibodies. It
      may prevent a potentially hazardous reduction of immunosuppression in persistent
      inflammation.

PMID- 12234277
TI  - Application of MARS artificial liver support as bridging therapy before split
      liver retransplantation in a 15-month-old child.
AB  - Molecular Adsorbent Recirculating System (MARS) is a blood-filtering system
      designed to provide biological artificial liver support. We describe its use in a
      small child to illustrate its effectiveness and practicality in this age group. A
      15-month-old male underwent split liver transplantation for acute liver failure
      following bone marrow transplantation. After development of graft dysfunction we
      instituted MARS-dialysis. MARS therapy led to a dramatic fall in serum bilirubin
      and transaminases. Liver synthetic function was not affected. This was
      accompanied by a stabilization of the patients clinical condition until repeat
      split liver transplantation was performed 2 weeks after the first graft. MARS
      dialysis is practical in the small child. In this case, it did not provide
      definitive treatment but was an excellent bridging therapy before
      retransplantation.

PMID- 12234278
TI  - Necrotizing fasciitis following liver and small intestine transplantation.
AB  - Necrotizing fasciitis is a rare, subcutaneous infection. It can occur in patients
      after solid-organ transplantation. We herein report two patients who developed
      necrotizing fasciitis following combined liver and small intestine
      transplantation. The first patient experienced this infection 4 yr after
      transplantation and 1 yr after the closure of the ileostomy. The second patient
      suffered from necrotizing fasciitis 2 days after the transplant. Both cases were
      diagnosed on the physical findings, culture of subcutaneous lavage, and the
      computed tomography findings. The site of entrance of the organism was not clear
      in either case. Both patients had a fulminant course and died within 1 week from
      the onset, despite aggressive surgical intervention. Therefore, necrotizing
      fasciitis has to be recognized as a potential complication of intestinal
      transplantation.

PMID- 12234279
TI  - Induction of a transient graft vs. leukemia effect following unrelated cord blood
      transplantation.
AB  - Umbilical cord blood (UCB) has become a frequent source of allogeneic
      hematopoietic stem cells for transplantation. Of theoretical concern is a
      potential decrease in the graft vs. leukemia (GvL) effect, given the lesser
      degree of graft vs. host disease (GvHD) with this donor source. We report a case
      of recurrent acute non-lymphoblastic leukemia (ANLL) following stem cell
      transplantation with unrelated mismatched UCB, which responded to the induction
      of GvHD. The response was documented both morphologically and by evaluation of
      chimeric engraftment by molecular DNA techniques. In addition, WT-1, a purported
      marker of minimal residual disease in acute leukemia, correlated with remission
      status in this patient. In summary, the GvL effect is seen with allogeneic UCB
      transplantation and has the potential to be induced along with GvHD.

PMID- 12234280
TI  - Fulminant recurrence of atypical hemolytic uremic syndrome during a calcineurin
      inhibitor-free immunosuppression regimen.
AB  - Recurrence of hemolytic uremic syndrome (HUS) after kidney transplantation is
      frequent, occurring almost exclusively in patients with atypical HUS, which is
      not caused by Escherichia coli gastroenteritis and in which diarrhea is absent.
      Calcineurin inhibitors are associated with recurrence of HUS. In two children who
      underwent living donor kidney transplantation for atypical HUS, we pre-emptively
      employed sirolimus in a calcineurin inhibitor-free immunosuppression regimen.
      Both children had excellent early graft function, yet both developed severe
      recurrent disease and subsequently lost their grafts. Avoidance of calcineurin
      inhibitors did not prevent recurrence of severe HUS and graft loss.
      Transplantation for severe atypical HUS remains problematic.

PMID- 12234281
TI  - Increasing arteriovenous fistulas in hemodialysis patients: problems and
      solutions.
AB  - National guidelines promote increasing the prevalence of fistula use among
      hemodialysis patients. The prevalence of fistulas among hemodialysis patients
      reflects both national, regional, and local practice differences as well as
      patient-specific demographic and clinical factors. Increasing fistula prevalence
      requires increasing fistula placement, improving maturation of new fistulas, and
      enhancing long-term patency of mature fistulas for dialysis. Whether a patient
      receives a fistula depends on several factors: timing of referral for dialysis
      and vascular access, type of fistula placed, patient demographics, preference of
      the nephrologist, surgeon, and dialysis nurses, and vascular anatomy of the
      patient. Whether the placed fistula is useable for dialysis depends on additional
      factors, including adequacy of vessels, surgeon's experience, patient
      demographics, nursing skills, minimal acceptable dialysis blood flow, and
      attempts to revise immature fistulas. Whether a mature fistula achieves long-term
      patency depends on the ability to prevent and correct thrombosis. An optimal
      outcome is likely when there is (1) a multidisciplinary team approach to vascular
      access; (2) consensus about the goals among all interested parties
      (nephrologists, surgeons, radiologists, dialysis nurses, and patients); (3) early
      referral for placement of vascular access; (4) restriction of vascular access
      procedures to surgeons with demonstrable interest and experience; (5) routine,
      preoperative mapping of the patient's arteries and veins; (6) close, ongoing
      communication among the involved parties; and (7) prospective tracking of
      outcomes with continuous quality assessment. Implementing these measures is
      likely to increase the prevalence of fistulas in any given dialysis unit.
      However, differences among dialysis units are likely to persist because of
      differences in gender, race, and co-morbidity mix of the patient population.

PMID- 12234282
TI  - RNA expression profiling as prognostic tool in renal patients: toward
      nephrogenomics.
AB  - Damage to the kidney generally elicits tissue repair mechanisms, but these
      processes themselves conversely may result in the progression of chronic renal
      disease. In a majority of patients chronic renal insufficiency progresses to a
      common histological end point, marked by the presence of a vast amount of scar
      tissue, that is, glomerulosclerosis and interstitial fibrosis. These lesions are
      the result of an excessive production of extracellular matrix (ECM) components.
      Studies on RNA expression in experimental kidney disease have shown that renal
      mRNA levels for ECM components and cytokines can function as prognostic tools.
      This suggests that mRNA levels potentially predict outcome and reaction to
      therapy in patients with renal diseases. Timely detection of molecular
      alterations could allow early therapeutic intervention that slows down or even
      prevents the development of sclerotic and fibrotic lesions. This review first
      provides a short introduction on mechanisms of initiation and progression of
      renal disease. Molecular techniques are available to identify renal RNA sequences
      potentially involved in disease progression. We discuss several molecular
      techniques that are being used in kidney research for quantitation and detection
      of mRNA. This is followed by a brief overview of investigation in experimental
      renal diseases, which reveal that alterations in tissue ECM mRNA levels precede
      histological damage and can function as predictors of clinical outcome. In
      particular, studies in human kidney biopsies that evaluate the prognostic value
      of mRNA levels with respect to renal function are examined, paying special
      attention to the pitfalls that potentially are encountered when interpreting the
      results of such studies. Then, we elaborate on ways of optimal exploitation of
      mRNA quantification as a prognostic tool. The potential and limitations of
      microarray technology in the search for genes specifically involved in
      progression of renal disease are reviewed, including RNA expression profiling and
      large-scale DNA mutation screening. Finally, the future utilities of microarray
      in nephrology and renal pathology are discussed.

PMID- 12234283
TI  - Cystinuria in children: distribution and frequencies of mutations in the SLC3A1
      and SLC7A9 genes.
AB  - BACKGROUND: Cystinuria is a common inherited disorder of defective renal
      reabsorption of cystine, ornithine, lysine and arginine leading to
      nephrolithiasis. Two responsible genes have been identified so far: Mutations in
      the SLC3A1 gene encoding the heavy chain rbAT of the renal cystine transport
      system rbAT/b(0,+)AT cause cystinuria type I, while variants in SLC7A9, the gene
      of its light chain b(0,+)AT, have been demonstrated in non-type I cystinuria. In
      this study, we searched for mutations in both genes in a cohort of children with
      cystinuria. METHODS: Twenty-one cystinuric children from 16 families were
      analyzed by mutational analysis of the genes SLC3A1 and the SLC7A9. The patients
      were classified by the urinary amino acid excretion profile of their parents.
      Additionally, 10 unclassified patients were screened for genomic variants. The
      screening techniques included single strand conformation polymorphism analysis,
      restriction assays and direct sequencing. RESULTS: Two novel mutations were
      identified in SLC3A1 and three in SLC7A9; three were missense mutations and two
      frameshift mutations. In the pediatric patients, mutations were found in 54% of
      type I (SLC3A1) and in 25% of non-type I (SLC7A9) chromosomes. For this group of
      patients a total detection rate of 46.6% for mutations in both genes was
      delineated. In the cohort of unclassified 10 patients, 70% of mutations were
      determined. M467T and G105R were the preponderant mutations in SLC3A1 and SLC7A9,
      respectively; T216M was the major mutation in Turkey and Greece. CONCLUSIONS: The
      detection rate for mutations in SLC3A1 and SLC7A9 in children was 54% in the
      SLC3A1 gene for type I chromosomes and 25% in the SLC7A9 gene for non-type I
      chromosomes. It was lower than that in 10 further patients with an unclassified
      cystinuria, although the clinical characterization in the first group was more
      stringent; additionally, different spectrums of mutations were observed. The lack
      of detectable mutations in many patients indicates the possibility of other yet
      unidentified genes involved in cystinuria. We could not correlate the severity of
      the disease to the type of cystinuria in the pediatric patients.

PMID- 12234284
TI  - Linkage of creatinine clearance to chromosome 10 in Utah pedigrees replicates a
      locus for end-stage renal disease in humans and renal failure in the fawn-hooded
      rat.
AB  - BACKGROUND: Renal failure is an important health concern for persons with
      hypertension and diabetes. In the fawn-hooded rat, a renal failure locus, Rf-1,
      has been identified on rat chromosome 1. A study of African American sibpairs
      with end-stage renal disease (ESRD) replicated this finding on the orthologous
      region in humans, chromosome 10, with a maximum logarithm of odds (LOD) score of
      3.4. An important question is whether this region can be detected in healthy
      subjects prior to onset of ESRD by examining creatinine clearance as an indicator
      of early renal damage. METHODS: We analyzed 49 Utah Caucasian pedigrees and
      performed quantitative nonparametric linkage analysis using 21 markers spanning
      chromosome 10. Pedigree members (mean age of 40 +/- 17) were examined up to three
      different times over 10 years, with creatinine clearance measured at each exam.
      For examination 1, three overnight, timed, 12-hour urine samples were obtained
      and averaged. One 12-hour sample was obtained for examinations 2 and 3. RESULTS:
      Heritabilities of creatinine clearance were 0.33 (N = 1360), 0.36 (N = 1196), and
      0.53 (N = 718) for the three examinations, respectively. The nonparametric LOD
      score for examination 1 was 1.4 at marker D10S677 (approximately 117 cM). The LOD
      score at examination 2, an average of 21/2 years later, was 1.8 at marker
      D10S1239 (approximately 123 cM) and 1.9 at marker D10S1425 (approximately 137
      cM). The LOD score at examination 3, an average of 10 years from baseline, was
      2.1 at marker D10S2470 (approximately 113 cM). Thus, there is consistent evidence
      of linkage to this region from three different examinations spanning a period of
      10 years. CONCLUSIONS: These linkage results confirm the ESRD linkage and the rat
      renal failure linkage to this region even though the LOD score is somewhat
      weaker, probably due to the less severe phenotype that was analyzed. It also
      suggests that there may be a locus on chromosome 10 that leads to reduced renal
      function that can be detected while subjects are still healthy. Identification of
      the responsible gene may help in predicting renal disease progression in
      susceptible patients.

PMID- 12234285
TI  - CTGF expression in mesangial cells: involvement of SMADs, MAP kinase, and PKC.
AB  - BACKGROUND: The induction of excess matrix in renal fibrosis seems to be
      mediated, at least in part, by the transforming growth factor-beta (TGF-beta)
      mediated induction of connective tissue growth factor (CTGF) in mesangial cells.
      METHODS: By examining CTGF protein and mRNA expression and promoter activity in
      the presence or absence of TGF-beta or inhibitors, the signaling pathways
      controlling basal and TGF-beta-induced CTGF expression in mesangial cells were
      investigated. RESULTS: TGF-beta enhances CTGF mRNA and protein expression in
      mesangial cells. Mutation of a consensus SMAD binding element in the CTGF
      promoter completely abolished TGF-beta-induced CTGF expression and reduced basal
      CTGF expression. The previously identified basal control element-1 (BCE-1) site,
      but not Sp1 contributes to basal CTGF promoter activity. Ras/MEK/ERK, protein
      kinase C (PKC) and tyrosine kinase activity also contribute to basal and TGF-beta
      induced CTGF promoter activity in cultured mesangial cells. CONCLUSIONS: The TGF
      beta-induction of CTGF in mesangial cells requires SMADs and PKC/ras/MEK/ERK
      pathways. SMADs are involved in basal CTGF expression, which presumably reflects
      the fact that mesangial cells express TGF-beta endogenously. TGF-beta also
      induces CTGF through ras/MEK/ERK. Inhibiting ras/MEK/ERK seems not to reduce
      phosphorylation (that is, activation) of SMADs, suggesting that SMADs, although
      necessary, are insufficient for the TGF-beta-stimulation of the CTGF promoter
      through ras/MEK/ERK. Thus, maximal TGF-beta induction of CTGF requires synergy
      between SMAD and ras/MEK/ERK signaling.

PMID- 12234286
TI  - Enhanced MCP-1 expression during ischemia/reperfusion injury is mediated by
      oxidative stress and NF-kappaB.
AB  - BACKGROUND: Renal ischemia/reperfusion injury is a major cause of acute renal
      failure in both native kidneys and renal allografts. One important feature of
      such injury is monocyte/macrophage infiltration into the renal tissue. The
      infiltration of monocytes/macrophages can be induced by chemotactic factors
      produced by renal cells. Monocyte chemoattractant protein-1 (MCP-1) is a potent
      chemoattractant protein for monocyte recruitment. The objective of the present
      study was to investigate mechanisms of elevated MCP-1 expression in rat kidney
      during ischemia/reperfusion injury. METHODS: The left kidney was subjected to one
      hour of ischemia followed by reperfusion for various time periods. The expression
      of MCP-1 mRNA was determined by nuclease protection assay and MCP-1 protein was
      identified by immunohistochemistry. Activation of a nuclear factor-kappa B (NF
      kappaB) was determined by electrophoretic mobility shift assay and the level of
      lipid peroxides in the kidney was measured. RESULTS: There was a significant
      increase in MCP-1 expression in the ischemia/reperfusion kidney 2 hours after
      reperfusion (210% of the control). This increase was accompanied by activation of
      NF-kappaB, suggesting that this transcription factor might be involved in the
      event. The number of monocytes was significantly elevated in the kidney 3 days
      after ischemia/reperfusion. Pretreatment of rats with NF-kappaB inhibitors not
      only prevented NF-kappaB activation induced by ischemia/reperfusion, but also
      inhibited MCP-1 mRNA expression. Further analysis revealed that oxidative stress
      and increased IkappaB-alpha phosphorylation might be an underlying mechanism for
      NF-kappaB activation and subsequent MCP-1 mRNA expression in the
      ischemia/reperfusion kidney. CONCLUSION: The present study clearly demonstrates
      that enhanced MCP-1 expression in rat kidney during ischemia/reperfusion injury
      is mediated by NF-kappaB activation and oxidative stress. Elevated MCP-1
      expression might be responsible for increased monocyte infiltration in the
      injured kidney.

PMID- 12234287
TI  - Metabolic acidosis up-regulates PTH/PTHrP receptors in UMR 106-01 osteoblast-like
      cells.
AB  - BACKGROUND: Metabolic acidosis results in skeletal demineralization by multiple
      mechanisms. One of these involves the inorganic phase of bone by which hydrogen
      ion is buffered by bone carbonate. In addition, the cellular components of bone
      participate by the induction and repression of several skeletal genes. Previous
      studies have suggested that the action of parathyroid hormone (PTH), a major
      regulator of bone turnover, might be altered by acidosis. The present studies
      were designed to test directly, in vitro, whether acidosis altered the effects of
      PTH in UMR 106-01 osteoblast-like cells. METHODS: Studies were conducted in
      confluent cultures of UMR 106-01 cells in modified Eagle's medium (MEM) with 5%
      fetal bovine serum (FBS) at pH values varying from 7.4 to 7.1 by addition of HCl.
      After time periods of 4 to 48 hours, cells were tested for cyclic AMP generation
      in response to PTH. PTH binding and PTH/PTHrP receptor mRNA levels were
      determined by radioligand binding assay and Northern analysis respectively.
      RESULTS: After 48 hours, decreases in pH from 7.4 to 7.1 resulted in a
      progressive increase in PTH-stimulated cyclic-AMP generation from 1978 +/- 294 to
      4968 +/- 929 pmol/culture/5 min (P < 0.05). Basal cyclic AMP concentrations were
      unchanged. PTH binding increased 1.5- to twofold. Competitive inhibition binding
      revealed an increase in receptor number supported by up-regulation of PTH/PTHrP
      receptor mRNA up to twofold from control levels. CONCLUSIONS: These findings
      demonstrate that metabolic acidosis stimulates the response to PTH in UMR 106-01
      osteoblast-like cells by a mechanism that involves an increase in the levels of
      PTH/PTHrP receptor mRNA. Thus, the skeletal response to acidosis that includes an
      increase in bone resorption may result, at least in part, from an increase in
      PTH/PTHrP receptors leading to an enhanced effect of PTH on bone.

PMID- 12234288
TI  - Smad7 mediates transforming growth factor-beta-induced apoptosis in mesangial
      cells.
AB  - BACKGROUND: In addition to inhibiting cell growth, transforming growth factor
      beta (TGF-beta) has recently been reported to induce apoptosis in various cell
      lines. Smad proteins are the downstream effectors of TGF-beta signaling. Among
      them, Smad7 exerts negative feedback control over the action of TGF-beta.
      However, we do not know how the Smad proteins contribute to TGF-beta-induced
      apoptosis in mesangial cells. To investigate the function of Smad proteins, we
      examined the effect of Smad overexpression using adenoviral vector in mesangial
      cells. METHODS: Primary cultured rat mesangial cells were transfected with Smad7
      promoter-luciferase-plasmid by electroporation. Smad7 promoter activity was
      investigated by luciferase assay. The apoptotic phenomena elicited by TGF-beta
      and Smad7 overexpression were investigated using adenoviral vector (AdCMV-Smad7).
      Apoptosis was detected by the cell death detection ELISA assay, CPP32/caspase-3
      assay, and nucleosomal DNA laddering. RESULTS: TGF-beta significantly increased
      the protein expression and the promoter activity of Smad7 in rat mesangial cells.
      Overexpression of Smad7 induced DNA fragmentation and significant increases in
      cell death ELISA and CPP32/caspase-3 assay. On the other hand, overexpression of
      Smad2 and Smad3 did not elicit any significant increases in CPP32/caspase-3
      activity. Furthermore, the antisense oligonucleotide to Smad7 prevented the TGF
      beta-induced apoptosis. Overexpression of Smad7 did not affect nuclear factor
      kappaB activity in mesangial cells. CONCLUSIONS: These data indicate that TGF
      beta-induced apoptosis in mesangial cells is mediated through the activation of
      caspase-3 by Smad7, but not by Smad2 or Smad3. Our results provide new
      clarification on the function of Smad7 in TGF-beta signaling in mesangial cells.

PMID- 12234289
TI  - High-protein induced renal enlargement is growth hormone independent.
AB  - BACKGROUND: Growth hormone (GH) and insulin-like growth factors (IGFs) have been
      postulated as pathogenic factors in several forms of renal growth, including that
      induced by high-protein (HP) diets. Compensatory renal growth (CRG) following
      renal uninephrectomy is strictly GH dependent, while the exact role of GH as a
      regulating factor in HP induced renal growth has not been fully clarified.
      METHODS: To elucidate a possible direct role for GH in HP-induced renal growth,
      we examined the effect of a newly developed specific GH-receptor (GHR) antagonist
      (B2036-PEG) on renal growth and renal GH/IGF-system expression in HP-fed mice.
      RESULTS: Mice fed a HP diet (45% protein) for one week demonstrated renal
      hypertrophy and increased renal IGF-I. GH receptor antagonist (GHRA) treatment
      neither modified renal IGF-I nor abolished the renal hypertrophy. In contrast,
      however, GHRA administration did modify renal mRNA expression of many members of
      the GH and IGF systems. CONCLUSIONS: The major new finding is that HP-induced
      renal growth in adult mice is GH independent.

PMID- 12234290
TI  - Reduced p21, p27 and vitamin D receptor in the nodular hyperplasia in patients
      with advanced secondary hyperparathyroidism.
AB  - BACKGROUND: In uremic patients with secondary hyperparathyroidism (2HPT), nodular
      hyperplasia of parathyroid gland shows a monoclonal pattern of cell
      proliferation, in which a decreased density of vitamin D receptor (VDR) also is
      demonstrated. The present study aimed at elucidating the mechanism of parathyroid
      cell proliferation in relation to cell cycle determinants in patients with
      advanced 2HPT. METHODS: The expression of cyclin-dependent kinase inhibitors, p21
      and p27, and VDR were examined and compared among four groups of nodular (Nd; N =
      23) or diffuse (Df; N = 6) hyperplastic parathyroid glands resected due to 2HPT,
      primary adenomas (Ad; N = 15), and histologically-normal parathyroid glands (C; N
      = 20) removed during thyroidectomy. Immunohistochemical analyses for VDR, p21,
      p27 and Ki67 antigen were performed in formalin-fixed paraffin-embedded tissues
      by using specific polyclonal antibody. The distribution and the intensity of
      immunoreactivity was quantified by using NIH imaging, and was expressed as the
      labeling index (LI) of positive nuclear staining in a random set of 1000 cells.
      RESULTS: p21 LI was significantly diminished in both Nd (85 +/- 110; mean +/- SD)
      and Ad (136 +/- 122) as compared to that in Df (360 +/- 191) or C (359 +/- 228; P
      < 0.01). p27 LI was also significantly diminished in both Nd (97 +/- 156) and Ad
      (187 +/- 196) as compared to that in Df (532 +/- 146) or C (631 +/- 170; P <
      0.01). VDR LI in Nd (162 +/- 194) was also significantly lower than that in Df
      (495 +/- 337), Ad (383 +/- 262), or C (659 +/- 234), respectively (P < 0.01).
      Parathyroid sections with high nuclear VDR expression elicited high p21 and p27
      expression. Both p21 and p27 LI in Nd correlated significantly with nuclear VDR
      LI (r = 0.92; P < 0.01, r = 0.76; P < 0.01), but not with p53 LI, and inversely
      correlated with the glandular weight (r = 0.44; P < 0.05, r = 0.41; P < 0.05).
      CONCLUSIONS: The reduced expression of p21 and p27, in a VDR-dependent manner, is
      a major pathogenic factor for a nodular parathyroid gland growth.

PMID- 12234291
TI  - Alterations of PPARalpha and its coactivator PGC-1 in cisplatin-induced acute
      renal failure.
AB  - BACKGROUND: In this study we examined whether a recently characterized
      coactivator of Peroxisome proliferator activated receptor alpha (PPARalpha),
      Peroxisome proliferator activated receptor-gamma-coactivator-1 (PGC-1) plays a
      role in the regulation of fatty acid oxidation during cisplatin-induced
      nephrotoxicity. METHODS: Studies in mouse kidneys used quantitative reverse
      transcription-polymerase chain reaction (RT-PCR) to measure peroxisomal acyl
      coenzyme A (acyl-CoA) and PGC-1 mRNA levels and in situ hybridization to localize
      PGC-1 mRNA. Studies in LLCPK1 cells used quantitative RT-PCR and biochemical
      assays to measure mRNA levels and enzyme activities of peroxisomal acyl-CoA,
      mitochondrial carnitine palmitoyl transferase (CPT) and PGC-1. Eletrophoretic
      mobility shift assays (EMSA) and Western blot analysis of nuclear extracts, and
      transient transfection of PGC-1 were used to examine the effect of cisplatin on
      PPARalpha-regulated fatty acid oxidation. RESULTS: Cisplatin decreased mRNA
      levels of peroxisomal acyl-CoA enzyme in mouse kidney and also reduced the mRNA
      levels and enzyme activities of acyl-CoA and mitochondrial CPT-1 in LLCPK1 cells.
      DNA-protein binding studies demonstrated that exposure to cisplatin reduces
      PPARalpha/retinoid X receptor (RXRalpha) binding activity. Immunoblotting studies
      demonstrated that cisplatin had no effect on nuclear levels of PPARalpha or
      RXRalpha protein. In situ hybridization studies in mouse kidney demonstrated the
      localization of PGC-1 mRNA to proximal tubules and thick ascending limb of Henley
      (TALH) cells. Cisplatin diminished the expression of PGC-1 mRNA levels in mouse
      kidney and also in LLCPK1 cells. Transient expression of PGC-1 shows the nuclear
      localization of PGC-1 protein and increased PPARalpha transcriptional activity in
      LLCPK1 cells. CONCLUSIONS: These results demonstrate that cisplatin deactivates
      PPARalpha by reducing its DNA binding activity and the availability of its tissue
      specific coactivator PGC-1.

PMID- 12234292
TI  - Renal tubulointerstitial injury in weanling rats with hyperhomocysteinemia.
AB  - BACKGROUND: While hyperhomocysteinemia is associated with an increased risk of
      atherosclerosis and the related cardiovascular diseases, the effect of
      hyperhomocysteinemia on the kidney has not been clearly demonstrated. The purpose
      of this study was to investigate whether long-term hyperhomocysteinemia develops
      atherosclerotic lesions in the kidney. METHODS: The effects of various dietary
      combinations, including folate deficiency, choline deficiency and methionine
      loading, on the plasma homocysteine concentration, renal function and renal
      histopathology were examined for 12 weeks in male weanling Fisher rats. RESULTS:
      Folate deficiency, choline deficiency and methionine loading synergistically
      induced hyperhomocysteinemia up to 69.7 +/- 23.1 micromol/L (control, 11.6 +/-
      3.9 micromol/L, P < 0.01) without any change in blood pressure. Creatinine
      clearance was negatively correlated with the plasma homocysteine concentration (r
      = -0.55, P < 0.01). Arterial and arteriolar wall thickening, and focal
      tubulointerstitial fibrosis were found in the kidneys of the hyperhomocysteinemic
      rat. The lesions of tubulointerstitial fibrosis appeared striped or wedge-shaped
      at the subcapsular cortex of the kidney. In addition, the expression of vascular
      endothelial growth factor, an indicator of hypoxia, was increased in the adjacent
      more intact area of the cortex. These findings suggest that the renal
      tubulointerstitial lesions were likely to be mediated by severe ischemia due to
      regional circulatory disturbance. Folate supplementation diminished these
      vascular and tubulointerstitial changes. CONCLUSION: These results indicate that
      diet-induced chronic hyperhomocysteinemia could induce vascular remodeling and
      tubulointerstitial injury in the kidney, and that these changes were ameliorated
      by folate supplementation.

PMID- 12234293
TI  - IGF-1-induced lipid accumulation impairs mesangial cell migration and contractile
      function.
AB  - BACKGROUND: Chronic treatment of mesangial cells with insulin-like growth factor
      1 (IGF-1) results in intracellular lipid accumulation. These mesangial cells
      resemble foam cells. METHODS: To determine whether this phenotype affects cell
      function, lipid-laden mesangial cells were tested for their ability to migrate in
      response to IGF-binding protein-5 (IGFBP-5) and to contract in response to
      angiotensin II (Ang II). IGFBP-5 binding and subsequent activation of the signal
      transduction cascade for migration were examined. To confirm that lipid
      accumulation was responsible for impaired contractility, lipid was removed from
      lipid-laden mesangial cells and the cells were re-tested for contractile response
      to Ang II. RESULTS: In comparison to control mesangial cells, lipid-laden cells
      failed to migrate in response to IGFBP-5. Although cellular binding of IGFBP-5
      was not altered by lipid accumulation, IGFBP-5 failed to activate cdc42, a Rho
      GTPase required for IGFBP-5-mediated mesangial cell migration. These data
      indicate that lipid accumulation within the mesangial cell interferes with the
      signal transduction response to IGFBP-5. In addition, mesangial cells treated
      with IGF-1 had reduced contraction to Ang II. When lipid accumulation was
      exaggerated by adding cholesteryl esters to the culture medium, mesangial cells
      failed to contract in response to Ang II. Following removal of excess lipid from
      these mesangial cells, the contractile response to Ang II was restored.
      CONCLUSIONS: IGF-1 induces lipid accumulation in mesangial cells, which impairs
      their ability to respond to specific migratory and contractile stimuli. These
      observations are relevant to understanding functional abnormalities in diseases
      where mesangial foam cells occur, such as focal and segmental glomerulosclerosis
      and diabetic nephropathy.

PMID- 12234294
TI  - Hepatocyte growth factor gene therapy retards the progression of chronic
      obstructive nephropathy.
AB  - BACKGROUND: Unilateral ureteral obstruction (UUO) is characterized by progressive
      tubular atrophy and interstitial fibrosis. Rupture of the balance between cell
      proliferation and apoptosis plays a critical role in renal atrophy. Hepatocyte
      growth factor (HGF) is a cytokine function on cell survival and tissue
      regeneration. We studied the effects and possible mechanisms of HGF gene therapy
      on tubular cell survival and anti-fibrosis in chronic obstructed nephropathy.
      METHODS: An in vivo transfection procedure of repeatedly transducing skeletal
      muscles with the HGF gene using liposomes containing the hemagglutinating virus
      of Japan (HVJ liposome) was tested on UUO rats. Expression of HGF and c-Met were
      examined by in situ hybridization, ELISA, or immunohistochemical staining.
      Interstitial fibrosis and macrophage infiltration were evaluated by Masson's
      Trichrome staining, alpha-smooth muscle actin and ED-1 immunostaining. Cell
      survival indices including proliferating cell nuclear antigen (PCNA), Bcl-2, Bcl
      xL and Bax were measured by immunohistochemistry and Western blots. Apoptosis was
      determined by the TUNEL method. RESULTS: After HVJ-HGF gene transfer, endogenous
      HGF and c-Met were up-regulated in UUO kidneys. Renal fibrosis, macrophage
      infiltration and tubular atrophy were suppressed both at day 14 and 28 after UUO
      (P < 0.05 or 0.01). Tubular cell proliferation was activated while apoptosis was
      inhibited, especially at the late stage of UUO. Bcl-2 was enhanced in the HGF
      transfected UUO rats, while no changes of Bcl-xL and Bax were found. CONCLUSIONS:
      In vivo HGF gene transfection retards the progression of chronic obstructed
      nephropathy and protects tubular cell survival in the long-term UUO model. Bcl-2
      rather than Bcl-xL or Bax may contribute to the anti-apoptotic function of HGF.

PMID- 12234295
TI  - Lipoteichoic acid from Staphylococcus aureus reduces renal ischemia/reperfusion
      injury.
AB  - BACKGROUND: The aim of this study was to investigate whether in vivo
      administration of a low, sub-lethal dose of lipoteichoic acid (LTA), a bacterial
      wall-fragment derived from the Gram-positive bacterium Staphylococcus aureus,
      protects the kidney against the renal dysfunction and injury caused by
      ischemia/reperfusion (I/R). METHODS: Male Wistar rats were administered LTA from
      S. aureus (1 mg/kg, IP). After 24 hours, rats were subjected to bilateral renal
      ischemia (45 min) followed by reperfusion (6 h). Serum and urinary markers were
      measured for the assessment of renal function, tubular and reperfusion-injury.
      Renal sections were used for histological grading of renal injury and for
      immunohistochemical localization of P-selectin, inducible nitric oxide synthase
      (iNOS) and nitrotyrosine (indicative of peroxynitrite formation). Kidney
      myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were measured for
      assessment of polymorphonuclear (PMN) cell infiltration and lipid peroxidation,
      respectively. Nitric oxide (NO) production was determined by measurement of
      plasma nitrite/nitrate levels. RESULTS: LTA pretreatment significantly reduced
      renal dysfunction, tubular and reperfusion-injury caused by I/R of the kidney as
      well as histological evidence of renal injury. LTA also reduced the expression of
      P-selectin and kidney MPO activity associated with renal I/R. MDA levels were
      significantly reduced by LTA pretreatment suggesting a reduction in the lipid
      peroxidation and formation of reactive oxygen species (ROS). LTA pretreatment
      also markedly reduced both the expression of iNOS and the formation of
      nitrotyrosine associated with renal I/R. Although LTA significantly reduced
      plasma nitrite/nitrate levels associated with I/R, nitrite/nitrate levels
      remained at levels significantly higher than that measured from the plasma
      obtained from Sham-operated animals. CONCLUSIONS: These data suggest, to our
      knowledge for the first time, that LTA pretreatment for 24 hours significantly
      reduces renal I/R injury. We propose that the mechanism of the protective effect
      involves reduction of the production of NO, ROS and peroxynitrite subsequent to
      reduced P-selectin and iNOS expression and PMN recruitment. However, although LTA
      pretreatment resulted in a reduction of iNOS expression and NO production, we
      hypothesize that the remaining significant levels of NO contribute to the
      beneficial actions provided by LTA.

PMID- 12234296
TI  - Expression of the chemokines MCP-1/CCL2 and RANTES/CCL5 is differentially
      regulated by infiltrating inflammatory cells.
AB  - BACKGROUND: Chemokines are involved in the regulation of the cellular renal
      infiltrate in glomerulonephritis; however, it is unclear to which degree resident
      glomerular cells or infiltrating leukocytes contribute to the formation of
      chemokines in glomerular inflammatory lesions. We therefore examined whether
      monocytes/macrophages play a role in the expression of the C-C chemokines MCP
      1/CCL2 and RANTES/CCL5 in renal tissue in a lipopolysaccharide (LPS)-induced
      model of inflammation, where previously we have shown increased glomerular RANTES
      expression and glomerular infiltration of ED-1-positive cells. METHODS:
      Inflammatory lesions were induced by an intraperitoneal injection of LPS. The
      infiltration of monocytes into the glomerulus was reduced by two experimental
      approaches. First, rats were depleted of monocytes by the use of specific
      monocyte-antisera or by cytotoxic drugs. Second, the infiltration of monocytes
      into the kidney was reduced by using intercellular adhesion molecule-1 (ICAM-1)
      knockout mice. RESULTS: Both experimental approaches demonstrated a significant
      reduction in the number of infiltrating monocytes/macrophages after
      lipopolysaccharide injection. This reduction in the infiltration of inflammatory
      cells was associated with significantly reduced RANTES/CCL5 mRNA expression.
      However, MCP-1/CCL2 mRNA expression was not inhibited after the LPS injection by
      monocyte/macrophage depletion. Also, the increase in nuclear factor-kappaB (NF
      kappaB) binding activity after the LPS injection was not reduced in pretreated
      animals. The experiments therefore demonstrate that infiltrating
      monocytes/macrophages contribute to increased RANTES/CCL5 mRNA expression in
      inflammatory renal lesions, whereas MCP-1/CCL2 mRNA expression and NF-kappaB
      activation were not reduced by monocyte/macrophage depletion. CONCLUSION: MCP
      1/CCL2 released from renal tissue upon stimulation plays a major role in the
      regulation of monocyte/macrophage infiltration, which contributes significantly
      to increased renal RANTES/CCL5 expression. This cross-talk between resident renal
      cells and monocytes/macrophages is therefore likely to boost the number of
      infiltrating inflammatory cells.

PMID- 12234297
TI  - Differential effects of 19-nor-1,25-(OH)(2)D(2) and 1alpha-hydroxyvitamin D(2) on
      calcium and phosphorus in normal and uremic rats.
AB  - BACKGROUND: Calcitriol, 1,25-(OH)(2)D(3) (1,25D), the most active metabolite of
      vitamin D, has been used in the treatment of secondary hyperparathyroidism (SH)
      because it controls parathyroid gland growth and suppresses parathyroid hormone
      (PTH) synthesis and secretion. Due to the calcemic and phosphatemic actions of
      1,25D, two analogs with potentially less side effects, 19-nor-1,25-(OH)(2)D(2)
      (19-nor) and 1alpha(OH)D(2) (1alphaD(2)) are currently being used in the
      treatment of SH. METHODS: This study compares the effects of these two analogs on
      calcium (Ca) and phosphorus (P) metabolism in normal, uremic, and
      parathyroidectomized (PTX) rats. Using doses of 50 to 250 ng of 19-nor or
      1alphaD(2), experiments were conducted in normal and uremic rats. RESULTS: In
      uremic rats, 19-nor did not increase plasma Ca or P while 1alphaD2 caused a dose
      dependent increase in both. In addition, while the Ca x P product remained
      unchanged in 19-nor-treated rats, it increased progressively with
      1alphaD(2)administration. In metabolic studies in normal rats treated with
      vehicle, 10 ng of 1,25D, 100 ng of 19-nor or 100 ng 1alphaD(2), intestinal
      calcium absorption and urinary calcium excretion were significantly higher in
      1alphaD(2)-treated rats compared to those receiving 19-nor. Similar results were
      seen for intestinal phosphorus absorption and urinary phosphorus excretion.
      Finally, the skeletal response to these two analogs was tested in PTX rats fed a
      calcium-deficient diet and treated daily with 100 ng of 19-nor or 1alphaD(2). The
      increase in plasma calcium in 1alphaD2-treated rats was markedly higher than in
      those receiving 19-nor. Similar results were seen in plasma phosphorus when these
      studies were repeated using a phosphorus-deficient diet. CONCLUSIONS: These
      studies demonstrate that when given in large doses to rats 19-nor is less
      calcemic and phosphatemic than 1alphaD(2). The lower Ca x P product in 19-nor
      treated rats may be an important consideration in patient therapy. Further
      studies in patients are necessary to define the clinical applicability of these
      differences.

PMID- 12234298
TI  - A role for extrarenal cells in the regeneration following acute renal failure.
AB  - BACKGROUND: Recovery of renal function following acute tubular necrosis (ATN) is
      dependent on the replacement of necrotic tubular cells with functional tubular
      epithelium. The source of these new tubular cells is thought to be resident renal
      tubular cells. The discovery of pluripotent bone marrow-derived stem cells has
      led to a reexamination of the cellular source and processes involved in the
      recovery from organ injury. METHODS: To test the hypothesis in humans that
      extrarenal cells participate in the recovery following ATN, we examined the
      origin of tubular cells in male patients with resolving ATN who had received a
      kidney transplant from a female donor. Immunohistochmistry of kidney biopsies was
      performed to identify renal tubular epithelial cells (cytokeratin positive) and
      leukocytes (CD45 positive). Fluorescent in-situ hybridization was used to detect
      Y chromosome containing cells with DAPI serving as a nuclear stain. All staining
      was performed on the same section. RESULTS: The Y chromosome was detected in
      approximately 40% of tubular cell nuclei in male kidneys (positive control) and
      in no nuclei of female kidneys (negative control). In male recipients of female
      kidneys who developed ATN, 1% of tubules contained Y chromosome cells defined by
      their morphology, positive staining for cytokeratin, and negative staining for
      CD45. When present, multiple cells in a positive tubule stained for the Y
      chromosome. No Y chromosome containing tubular cells were seen in similar sex
      mismatched transplants in male recipients who did not develop ATN, suggesting
      that recipient derived cells do not routinely repopulate the transplanted kidney.
      CONCLUSIONS: This proof-of-principle clinical observation demonstrates that
      extrarenal cells can participate in the regenerative response following ATN.
      These findings provide rationale for the cellular therapy of acute renal failure.

PMID- 12234300
TI  - A shift in the Bax/Bcl-2 balance may activate caspase-3 and modulate apoptosis in
      experimental glomerulonephritis.
AB  - BACKGROUND: Although apoptosis has been linked to the renal cell deletion and
      ensuing renal fibrosis, its regulating mechanisms remain obscure. Of the known
      regulators of apoptosis, the best characterized is the Bax to Bcl-2 ratio.
      However, its importance in controlling apoptosis in glomerulonephritis is
      unclear. Here, using the nephrotoxic nephritis (NTN) model, we evaluated Bax/Bcl
      2 in relation to changes in the apoptosis co-ordination enzyme, caspase-3.
      METHODS: Kidneys were harvested at days 7, 15, 30 and 45 post-injection of anti
      glomerular basement membrane antibody into Wistar Kyoto rats. These were analyzed
      for apoptosis (in situ end labeling of fragmented DNA, light and electron
      microscopy), Bax/Bcl-2 protein (Western blotting), mRNA (Northern blotting) and
      distribution (immunohistochemistry), as well as caspase-3 activity (substrate
      cleavage assay), inflammation (ED1 staining), proliferation (proliferating cell
      nuclear antigen staining) and fibrosis (Masson's Trichrome staining). RESULTS:
      Bax mRNA was significantly increased while that of Bcl-2 was decreased throughout
      the time course (+265% and -62% by day 45). Increased Bax and decreased Bcl-2
      protein were noted, significantly so on day 7 (+177% and -21%) and day 45 (+363%
      and -17%). Bax protein was observed in dilated and atrophic tubules, sclerotic
      glomeruli and inflamed interstitium, while Bcl-2 was only visible in atrophic
      tubules. The ratios of Bax to Bcl-2 mRNA and protein were significantly increased
      at all time points. These correlated (P < 0.05) with up-regulated caspase-3
      activity (r = 0.742 and 0.531), apoptosis (r = 0.712 and 0.540), proliferation (r
      = 0.611, mRNA only), inflammation (ED1+, r = 0.474 and 0.419) and fibrosis (r =
      0.474 and 0.729). CONCLUSIONS: Our findings suggest that the changes in the ratio
      of Bax to Bcl-2 may contribute to the caspase-3 activation and the modulation of
      renal apoptosis associated with renal inflammation, tubular atrophy and renal
      fibrosis in experimental glomerulonephritis.

PMID- 12234299
TI  - Triptolide is a potent suppressant of C3, CD40 and B7h expression in activated
      human proximal tubular epithelial cells.
AB  - BACKGROUND: Previous studies have shown that triptolide possesses potent
      immunosuppressive and anti-inflammatory properties. Increasing recognition of the
      importance of the proximal tubular epithelial cells (PTEC) in renal disease and
      renal transplantation raises the question of whether triptolide suppresses the
      pro-inflammatory activity of PTEC. METHODS: Cultured human PTEC were exposed to
      tumor necrosis factor-alpha (TNF-alpha) and immunosuppressant (triptolide or CsA
      or FK506) for 24 hours, followed by RT-PCR, ELISA, flow cytometry and Western
      blotting analysis for complement C3, CD40, B7h expression. RESULTS: TNF-alpha up
      regulated C3, CD40 and B7h production by PTEC. This up-regulation was inhibited
      by all three immunosuppressants with different intensity. Firstly, triptolide (4
      to 8 ng/mL), CsA (4000 to 6000 ng/mL) and FK506 (2000 ng/mL) inhibited up
      regulation of C3 mRNA, but CsA and FK506 had less of an effect than triptolide.
      Secondly, triptolide (4 to 8 ng/mL) completely inhibited C3 expression at both
      mRNA and protein levels. In contrast, CsA and FK506 had only slight effects on C3
      expression at the protein level. Thirdly, triptolide (4 to 8 ng/mL), CsA (500 to
      2500 ng/mL) and FK506 (1250 ng/mL) inhibited up-regulation of CD40 and B7h mRNA,
      the effect on B7h and CD40 mRNA expression by CsA and FK506 being greater than
      that on C3 mRNA expression. CONCLUSION: Triptolide effectively inhibited up
      regulation of C3, CD40 and B7h on PTEC. Triptolide was more effective than CsA
      and FK506 at inhibiting C3 expression. This suggests that triptolide, at non
      cytotoxic concentrations, has the potential to reduce the inflammatory and
      immunostimulatory properties of PTEC, in addition to any of the previously
      reported actions on T cell or B cell function.

PMID- 12234301
TI  - Differential expression of proteins in renal cortex and medulla: a proteomic
      approach.
AB  - BACKGROUND: Western blotting has previously been used to identify changes in
      protein expression in renal tissue. However, only a few proteins can be studied
      in each experiment by Western blot. We have used proteomic tools to construct
      protein maps of rat kidney cortex and medulla. METHODS: Expression of proteins
      was determined by silver stain after two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE). Protein spots were excised and digested with trypsin.
      Peptide masses were identified by MALDI-TOF mass spectrometry. The Mascot search
      engine was used to analyze the peptide masses and identify the proteins. RESULTS:
      Seventy-two proteins were identified (54 unique proteins) out of approximately
      1000 spots visualized on each gel. Most of the spots were expressed both in
      cortex and medulla. Of the identified proteins, three were expressed only in
      medulla and one only in cortex. Nine proteins were expressed in both regions but
      to a greater extent in cortex and three proteins were expressed more in medulla.
      Differential expression was confirmed for three proteins by Western blot.
      CONCLUSIONS: A large group of proteins and their relative expression levels from
      cortical and medullary portions of rat kidneys were found. Sixteen proteins are
      differentially expressed. Proteomics can be used to identify differential
      expression of proteins in the kidney on a large scale. Proteomics should be
      useful to detect changes in renal protein expression in response to a large range
      of physiological and pathophysiological stimuli.

PMID- 12234302
TI  - Nitric oxide/platelet activating factor cross-talk in mesangial cells modulates
      the interaction with leukocytes.
AB  - BACKGROUND: Platelet activating factor (PAF) and nitric oxide (NO) exert opposite
      effects on adherence and activation of circulating leukocytes to endothelium.
      Several studies have implicated the production of PAF and NO by mesangial cells
      in the regulation of glomerular filtration, permeability and inflammation.
      However, the reciprocal interaction between PAF and NO in mesangial cells and
      their role in leukocyte adhesion has not been investigated. METHODS: We evaluated
      whether blockade of constitutive production of NO by two different NO synthase
      (NOS) inhibitors (L-NAME and L-NMMA) could modulate PAF synthesis, and conversely
      whether exogenous PAF could influence the production of NO by mesangial cells. We
      evaluated whether modulation of PAF synthesis by NOS inhibitors could affect
      leukocyte adhesion to mesangial cells. The effect of PAF-receptor antagonist
      WEB2170, of anti-beta(2) integrins and intracellular adhesion molecule-1 (ICAM-1)
      blocking antibodies and of soluble Sialyl-Lewis-a also was evaluated. RESULTS:
      Blockade of NO synthesis by NOS inhibitors induced a spontaneous synthesis of PAF
      that was conversely inhibited by NO generation. On the other hand, PAF inhibited
      both the basal and l-arginine induced synthesis of NO by mesangial cells.
      Moreover, NOS inhibition promoted the adhesion of polymorphonuclear cells and
      monocytes to mesangial cells by a mechanism dependent on the synthesis of PAF and
      on the interaction of beta(2) integrins and ICAM-1. CONCLUSIONS: These data
      indicate that PAF and NO exhibit a bi-directional effect on their respective
      synthesis in human mesangial cells, and suggest that their reciprocal regulation
      may be relevant for leukocyte adhesion to glomerular mesangial cells.

PMID- 12234303
TI  - Specific therapy of digoxin intoxication in dogs by hybrid kidney overexpressing
      multidrug resistance protein.
AB  - BACKGROUND: We have recently developed a unique hybrid artificial kidney, where
      the proximal tubular cell line, over-expressing multidrug resistance protein, MDR
      1 (PCTL-MDR), was cultured on hollow fibers. While this module efficiently
      removed digoxin in vitro, its efficacy in vivo remained to be determined.
      METHODS: The system was scaled up by connecting 10 similar modules in parallel,
      with the MDR-1 (PCTL-MDR) overexpressed proximal tubular cell line cultured as in
      our previous study. The system was connected to dogs intoxicated with digoxin, a
      representative substrate of MDR-1. Blood was circulated for 90 minutes through
      the system. Arterial and venous blood concentrations of digoxin and inulin were
      monitored. Complete blood cell count and granulocyte elastase were measured
      before and at the end of the study. RESULTS: By using the system with PCTL-MDR,
      the arterial digoxin concentration was dramatically decreased from 2.89 +/- 0.10
      to 0.92 +/- 0.11 ng/mL, but not by the system with PCTL alone. The clearance was
      22.4 +/- 2.1 and 1.5 +/- 0.2 mL/min for the PCTL-MDR and PCTL equipment,
      respectively. Inulin was not transported in either system. White blood cell and
      platelet counts were slightly reduced by the treatment while hematocrit was
      unchanged; the granulocyte elastase concentration was slightly increased.
      CONCLUSION: These data suggest that our new type of hybrid kidney can selectively
      remove digoxin sufficiently to reduce its systemic blood concentration in dogs
      with digoxin intoxication. Taking previous studies into consideration, this
      system may be a more powerful tool for the treatment of intoxication.

PMID- 12234304
TI  - Protective role of nitric oxide in mice with Shiga toxin-induced hemolytic uremic
      syndrome.
AB  - BACKGROUND: Nitric oxide (NO) is an endogenous vasodilator and platelet
      inhibitor. An enhanced NO production has been detected in patients with hemolytic
      uremic syndrome (HUS), although its implication in HUS pathogenesis has not been
      clarified. METHODS: A mouse model of Shiga toxin 2 (Stx2)-induced HUS was used to
      study the role of NO in the development of the disease. Modulation of l-arginine
      NO pathway was achieved by oral administration of NO synthase (NOS) substrate or
      inhibitors, and renal damage, mortality and platelet activity were evaluated. The
      involvement of platelets was studied by means of a specific anti-platelet
      antibody. RESULTS: Inhibition of NO generation by the NOS inhibitor L-NAME
      enhanced Stx2-mediated renal damage and lethality; this effect was prevented by
      the addition of l-arginine. The worsening effect of L-NAME involved enhanced Stx2
      mediated platelet activation, and it was completely prevented by platelet
      depletion. CONCLUSIONS: NO exerts a protective role in the early pathogenesis of
      HUS, and its inhibition potentiates renal damage and mortality through a
      mechanism involving enhanced platelet activation.

PMID- 12234305
TI  - Vasopeptidase inhibition and Ang-(1-7) in the spontaneously hypertensive rat.
AB  - BACKGROUND: Omapatrilat, a new vasopeptidase inhibitor, inhibits the activity of
      angiotensin-converting enzyme (ACE) and neutral endopeptidase 24.11 (NEP).
      Because these two enzymes participate in the degradation of the vasodilator and
      natriuretic peptide, angiotensin-(1-7) [Ang-(1-7)], we assessed whether
      omapatrilat treatment is associated with changes in the plasma and urinary
      excretion rates of the angiotensins. METHODS: We investigated in spontaneously
      hypertensive rats (SHR) (0.24 kg body weight) the effect of omapatrilat on plasma
      and urinary concentrations of angiotensin (Ang) I, Ang II and Ang-(1-7) during 17
      days of administration of either the drug (N = 15, 100 micromol/kg/day) or
      vehicle (N = 14) in the drinking water. Hemodynamic and renal excretory function
      studies were associated with histological examination of the expression of Ang-(1
      7) in the kidneys of both vehicle and omapatrilat-treated SHRs. RESULTS:
      Omapatrilat induced a sustained lowering of systolic blood pressure (-68 mm Hg)
      without changes in cardiac rate. The mild positive water balance produced by
      omapatrilat did not cause natriuresis or kaliuresis, although it was associated
      with a significant decrease in urine osmolality. Blood pressure normalization was
      accompanied by increases in plasma Ang I (2969%), Ang II (57%), and Ang-(1-7)
      (163%) levels, paralleling pronounced increases in urinary excretion rates of Ang
      I and Ang-(1-7) but not Ang II. Detection of Ang-(1-7) immunostaining in the
      kidneys of five other SHR exposed either to vehicle (N = 3) or omapatrilat (N =
      2) ascertained the source of the Ang-(1-7) found in the urine. Intense Ang-(1-7)
      staining, more pronounced in omapatrilat-treated SHR, was found in renal proximal
      tubules throughout the outer and inner regions of the renal cortex and the thick
      ascending loop of Henle, whereas no Ang-(1-7)-positive immunostaining was found
      in glomeruli and distal tubules. CONCLUSIONS: Omapatrilat antihypertensive
      effects caused significant activation of the renin-angiotensin system associated
      with increases in urinary excretion rates of Ang I and Ang-(1-7). Combined
      studies of Ang-(1-7) metabolism in urine and immunohistochemical studies in the
      kidney revealed the existence of an intrarenal source, which may account for the
      pronounced increase in the excretion rate of the vasodilator heptapeptide. These
      findings provide further evidence for a contribution of Ang-(1-7) to the
      regulation of renal function and blood pressure.

PMID- 12234306
TI  - Enhanced adherence of human uremic erythrocytes to vascular endothelium: role of
      phosphatidylserine exposure.
AB  - BACKGROUND: The exposure of phosphatidylserine (PS) on the outer leaflet of
      erythrocyte membrane may have several pathophysiological consequences including
      increased erythrocyte adherence to endothelial cells, a finding that seems
      relevant in pathologies with reported vascular injury. METHODS: Because PS
      externalization increases in erythrocytes from patients suffering from chronic
      uremia, which is frequently associated with vascular damage, the adherence of
      uremic erythrocytes to human umbilical vein endothelial cell (HUVEC) monolayers
      and the role of PS exposure on such cell-cell interaction were studied. RESULTS:
      The number of uremic erythrocytes adhering to HUVEC was markedly greater than
      with normal erythrocytes and significantly correlated (r = 0.88) with the
      percentage of PS-exposing erythrocytes in the population. Adhesion to the
      monolayers was significantly decreased when uremic erythrocytes were preincubated
      with either annexin V or PS-containing liposomes, and was strongly greater for PS
      positive than PS-negative fluorescence-activated cell sorter (FACS)-sorted uremic
      erythrocytes. Binding occurred preferentially in the gaps of HUVEC monolayers and
      was enhanced by matrix exposure. Uremic erythrocytes adhered to immobilized
      thrombospondin, and binding to endothelial cells was significantly reduced when
      monolayers were incubated with antibodies to thrombospondin. CONCLUSIONS: These
      findings suggest that PS externalization may promote increased uremic erythrocyte
      adhesion to endothelium, possibly via a direct interaction with matrix
      thrombospondin.

PMID- 12234307
TI  - Sexual dimorphism in renal ischemia-reperfusion injury in rats: possible role of
      endothelin.
AB  - BACKGROUND: Postischemic organ dysfunction is influenced by gender and sexual
      steroids. METHODS: To compare the susceptibility of the kidney to postischemic
      failure between sexes, the left vascular pedicle was clamped for 50 minutes in
      anesthetized male and female Wistar rats. Survival rate, renal and systemic
      hemodynamics and renal prepro-endothelin (pp-ET) mRNA expression were measured.
      RESULTS: Eight percent of males as compared to 75% of females survived for more
      than 7 days. Previous orchidectomy of mature rats or sexual immaturity improved
      the rate of 7 day survival to 67% and 58%, respectively, as compared to intact
      males (P < 0.05). Estradiol treatment of mature male animals also resulted in a
      significantly better survival. Ovariectomy, sexual immaturity or testosterone
      treatment had no impact on the course of renal failure in females. The early
      postischemic recovery of renal blood flow was delayed due to a dramatic increase
      in renal vascular resistance in male versus female rats. The expression of pp-ET
      gene in the kidneys was increased at 5 minutes following reperfusion and was
      significantly higher 2 hours after ischemia in males, but not in females.
      Pretreatment with the endothelin A receptor antagonist LU 135252 provided
      indistinguishable survival rates in intact male and female rats after warm renal
      ischemia. CONCLUSION: Female rats enjoy relative protection against postischemic
      renal failure. Furthermore, in intact males the effects of androgens upon
      ischemic kidney damage seem to be mediated by endothelin-induced vascular
      changes.

PMID- 12234308
TI  - Oral L-arginine does not improve endothelial dysfunction in children with chronic
      renal failure.
AB  - BACKGROUND: Cardiovascular disease is a major cause of mortality amongst patients
      with chronic renal failure (CRF). L-arginine has been used to improve endothelial
      function by increasing nitric oxide (NO) bioavailability and in animal models
      this in turn has attenuated the progression of atherosclerosis. We examined
      whether dietary L-arginine supplementation improved endothelial function in
      children with CRF. METHODS: A randomized, double-blind, placebo-controlled,
      crossover trial of L-arginine was conducted in 21 normotensive children aged 11.5
      +/- 3 (7 to 17) years with CRF (GFR 27.4 +/- 13.2 mL/min/1.73 m(2)) in whom
      endothelial dysfunction had previously been demonstrated. We examined the effect
      of L-arginineon the endothelial response to shear stress (NO-dependent) using a
      non-invasive technique of high-resolution ultrasound. Each subject was studied
      before and after 4 weeks of L-arginine (2.5 g/m(2) or 5 g/m(2) x 3/day) or
      placebo, separated by a rest period of 4 weeks. Brachial artery diameter was
      measured at rest, during increased flow (endothelial-dependent dilation) and
      after 25 microg of glyceryl trinitrate (endothelial-independent dilation) at each
      visit. RESULTS: After oral L-arginine, plasma L-arginine levels rose from 82 +/-
      20 to 179 +/- 110 micromol/L (P < 0.001). No significant change in endothelial
      dependent dilation during L-arginine (7.96 +/- 2.35 to 7.71 +/- 3.22%; P> 0.05)
      or placebo (8.2 +/- 2.89 to 8.3 +/- 3.14%; P> 0.05) was noted. There was no
      change in endothelial-independent dilation. CONCLUSION: Endothelial function was
      not improved with L-arginine, suggesting that dietary supplementation is not a
      useful clinical approach in children with CRF.

PMID- 12234309
TI  - Interstitial inflammation, sodium retention, and the pathogenesis of nephrotic
      edema: a unifying hypothesis.
AB  - BACKGROUND: The pathophysiology of edema in the nephrotic syndrome is
      controversial. Some investigators believe that sodium retention may result from a
      primary renal defect that causes an "overfilled" blood volume. In contrast, other
      authors believe that fluid escapes the vascular compartment due a low oncotic
      pressure, and sodium retention is a compensatory physiological response to an
      "underfilled" blood volume. The patients that best fit the "underfilled"
      hypothesis are children with minimal-change nephrotic syndrome (MCNS). METHODS:
      We analyzed critically the available evidence for and against each proposed
      pathogenic mechanism in the light of recent evidence indicating that the
      inflammatory infiltrate may play a role in primary renal sodium retention.
      RESULTS: Inflammatory infiltrate in the kidney is a constant characteristic in
      nephrotic syndrome associated with primary sodium retention and it is absent in
      most cases of MCNS in children CONCLUSIONS: We propose that primary sodium
      retention in the nephrotic syndrome depends on the existence and the intensity of
      renal inflammatory infiltrate, conspicuously absent in most cases of MCNS in
      children and present in other conditions associated with massive proteinuria. The
      tubulointerstitial inflammatory infiltrate is associated with increased
      vasoconstrictive mediators that result in increased tubular sodium reabsorption
      and with glomerular hemodynamic changes that reduce filtered sodium load.

PMID- 12234310
TI  - Autosomal-dominant medullary cystic kidney disease type 1: clinical and molecular
      findings in six large Cypriot families.
AB  - BACKGROUND: Autosomal-dominant medullary cystic kidney disease (ADMCKD), a
      hereditary chronic interstitial nephropathy, recently attracted attention because
      of the cloning or mapping of certain gene loci, namely NPHP1, NPHP2 and NPHP3 for
      familial juvenile nephronophthisis (NPH) and MCKD1 and MCKD2 for the adult form
      of medullary cystic kidney disease. Our aim was to present and discuss the
      clinical, biochemical, sonographic and histopathological findings in six large
      Cypriot families in whom molecular analysis has confirmed linkage to the MCKD1
      locus on chromosome 1q21. METHODS: The clinical, biochemical, sonographic and
      histopathological findings in 186 members of six large Cypriot families with
      ADMCKD-1 are presented. Creatinine clearance was calculated according to the
      Cockroft-Gault formula and was corrected to a body surface area (BSA) of 1.73 m2.
      DNA linkage analysis was performed with previously identified flanking
      polymorphic markers. RESULTS: This disease is characterized by the absence of
      urinary findings in the vast majority of patients, leading to end-stage renal
      failure (ESRF) at a mean age of 53.7 years. Hypertension and hyperuricemia are
      common, especially in males, the former encountered more frequently in advanced
      chronic renal failure (CRF). Gout has been noted in a small percentage of male
      patients. Loss of urinary concentrating ability was not a prominent early feature
      of the disease, while severe natriuresis was observed in a few males toward ESRF.
      Renal cysts are mainly corticomedullary or medullary, and they are present in
      about 40.3% of patients and appear more frequently near ESRF. CONCLUSION: ADMCKD
      type 1 is a common cause of ESRF among our dialysis population. The disease is
      difficult to diagnose clinically, particularly in the early stage when renal
      cysts are not usually present, making them a weak diagnostic finding. A dominant
      pattern of inheritance and DNA linkage analysis are helpful in the diagnosis of
      this disease.

PMID- 12234311
TI  - Delivery of erythropoietin by encapsulated myoblasts in a genetic model of severe
      anemia.
AB  - BACKGROUND: Existing animal models of anemia inadequately reflect the hematocrit
      usually present in chronic renal failure (CRF) patients and do not permit long
      term treatment studies. The transgenic mouse strain 134.3LC (Epo-TAg(H)) displays
      a severe chronic anemia resembling that observed clinically during CRF, while
      displaying an active, normal life span. This phenotype makes it a particularly
      interesting mouse model for testing erythropoietin (Epo)-based gene transfer
      strategies. METHODS: Ex vivo gene therapy was employed to administer mouse Epo to
      homozygous anemic Epo-TAg(H) mice. Encapsulated C(2)C(12) myoblasts genetically
      engineered to secrete 163 IU mouse Epo/10(6) cells/day were subcutaneously
      transplanted on the dorsal flank of the mice. Efficacy of delivered Epo was
      monitored by weekly measurements of animal hematocrit. RESULTS: Most treated
      homozygous Epo-TAg(H) mice displayed only a transient rise in hematocrit before
      eventually decreasing to levels as low as 3%. Administering the immunosuppressor
      anti-CD4+ monoclonal antibody (mAb) to homozygous Epo-TAg(H) mice, beginning at
      the time of implantation, permitted a rise in hematocrit that remained stable at
      elevated levels in cases of continued immunosuppression. CONCLUSIONS: Mice having
      the T antigen insertion in both Epo alleles appeared to develop an immune
      response to the natural mouse Epo delivered by encapsulated cells. By preventing
      this reaction using immunosuppression, we demonstrate that encapsulated myoblasts
      can deliver therapeutic doses of mouse Epo systemically and restore hemopoiesis
      in a genetic model of severe anemia.

PMID- 12234312
TI  - Mild renal insufficiency is associated with increased cardiovascular mortality:
      The Hoorn Study.
AB  - BACKGROUND: Cardiovascular mortality is extremely high in end-stage renal
      disease. Cardiovascular mortality risk also is increased in selected (high-risk)
      individuals with mild to moderate impairment of renal function. It is not clear
      whether a similar association exists in the general population and, if so,
      through what mechanisms. We investigated the association of renal function with
      all-cause and cardiovascular mortality in a population-based cohort and explored
      potential mechanisms underlying any such relationship. METHODS: An age-, sex-,
      and glucose-tolerance-stratified sample (N = 631) of a population-based cohort
      aged 50 to 75 years was followed prospectively. After up to 10.2 years of follow
      up, 117 subjects had died (50 of cardiovascular causes). At baseline, renal
      function was estimated by the serum creatinine level, the Cockcroft-Gault formula
      and Levey's equation. RESULTS: At baseline, the mean age was 64 +/- 7 years, 48%
      were men, 55% had hypertension, and 27% (by design) had type 2 diabetes. Serum
      creatinine was 91.7 +/- 19.0 micromol/L; creatinine clearance as estimated by the
      Cockroft-Gault formula was 72.5 +/- 13.7 mL/min/1.73 m(2), and the glomerular
      filtration rate (GFR) estimated by Levey's equation was 67.8 +/- 12.1 mL/min/1.73
      m(2). Renal function was inversely associated with all-cause and with
      cardiovascular mortality. Relative risks (95% confidence intervals) were 1.08
      (1.04 to 1.13) and 1.11 (1.07 to 1.16) per 5 micromol/L increase of serum
      creatinine; 1.07 (0.98 to 1.17) and 1.15 (1.01 to 1.31) for each decrease of 5
      mL/min/1.73 m(2) creatinine clearance; and 1.15 (1.05 to 1.26) and 1.26 (1.12 to
      1.42) for each decrease of 5 mL/min/1.73 m(2) of GFR. These associations remained
      after adjusting for age, sex, glucose tolerance status, hypertension, prior
      cardiovascular disease, low-density lipoprotein cholesterol, homocysteine,
      (micro)albuminuria, von Willebrand factor, soluble vascular adhesion molecule-1
      and C-reactive protein. Analyses in diabetic and hypertensive subjects gave
      similar results. CONCLUSION: Mild to moderate loss of renal function is strongly
      associated with an increased risk of cardiovascular mortality. The mechanism
      behind this association is unclear but does not appear to involve common risk
      factors such as hypertension, diabetes or hyperhomocysteinemia. Estimation of
      renal function by relatively simple methods therefore may be a valuable tool for
      cardiovascular risk assessment over and above that provided by conventional risk
      factors. Our results were obtained in a general middle-aged to elderly
      population, and thus have broad applicability.

PMID- 12234313
TI  - Inflammatory signals associated with hemodialysis.
AB  - BACKGROUND: Inflammation is highly prevalent in chronic hemodialysis patients.
      Because hemodialysis involves the contact of blood with "foreign" surfaces, and
      the documented activation of several humoral and cellular pathways during the
      procedure, the hemodialysis procedure has been suggested as a potential source of
      inflammation in this patient population. Earlier studies did not provide clear
      cut evidence of the potential contribution of the hemodialysis procedure to
      inflammation, as assessed by markers of inflammation such as cytokine levels and
      acute-phase protein production. METHODS: Nine patients were studied using primed
      constant infusion of l-(l-13C) leucine 2 hours before, during, and 2 hours after
      a single hemodialysis session. We evaluated the effects of hemodialysis on
      induction of interleukin-6 (IL-6) production as well as the fractional synthetic
      rates (FSR) of albumin and fibrinogen, two well-known acute-phase proteins.
      RESULTS: During hemodialysis, albumin FSR and fibrinogen FSR increased
      significantly compared to the measurements obtained during baseline period.
      During this period, albumin and fibrinogen FSR increased 64% and 34%,
      respectively, compared to baseline (P < 0.05). While the increase in IL-6
      concentration was modest during hemodialysis (14%), the levels further increased
      at the end of the 2-hour post-hemodialysis period (68% higher compared to
      baseline, P < 0.05). Fibrinogen FSR also demonstrated a further increase during
      the post-dialysis period (17% higher compared to the intradialytic period and 58%
      higher compared to baseline), while albumin FSR stabilized during this period.
      CONCLUSIONS: The results provide clear evidence of hemodialysis-induced
      inflammatory response. The process is most notable during the 2-hour post
      hemodialysis period.

PMID- 12234314
TI  - C-reactive protein and cardiovascular disease in peritoneal dialysis patients.
AB  - BACKGROUND: Elevated plasma concentrations of C-reactive protein (CRP) is a risk
      factor for cardiovascular disease (CVD) in the general population and in
      hemodialysis patients. The prognostic value of CRP is less well known in
      peritoneal dialysis (PD) patients. We examined the association between CRP and
      cardiovascular event (CVE) in a large population of PD patients. METHODS: Two
      hundred and forty patients starting PD were enrolled in this prospective study.
      The role of CRP was analyzed with respect to other known cardiovascular risk
      factors. RESULTS: The patients were followed for a mean duration of 41 +/- 21
      months; the median value of CRP was 7 mg/L. Eighty-nine cardiovascular events
      (CVE; 37.1%) occurred in 84 patients and the CRP levels were higher in patients
      who experienced CVE (27 +/- 14 vs. 6 +/- 8 mg/L; P < 0.0001). In the Cox model,
      patients in the three lower quartiles of the CRP levels had a decreased risk of
      CVE compared with those in the highest quartile. Cox regression analysis also
      revealed that age, a previous history of cardiovascular disease,
      hyperhomocysteinemia and hypoalbuminemia were risk factors for CVE. CRP levels
      were higher in patients who died during the study period (25 +/- 12 vs. 5 +/- 8
      mg/L; P = 0.003). In the Cox model, patients with CRP levels above the median had
      an increased risk of death compared with those in the lowest quartile.
      CONCLUSIONS: Chronic inflammation, as reflected by elevated CRP levels, is
      frequent in patients starting PD and independently contributes to an increased
      incidence of CVE in this population.

PMID- 12234315
TI  - A comparison of transplant outcomes in peritoneal and hemodialysis patients.
AB  - BACKGROUND: Studies examining the effect of pre-transplant dialysis modality on
      graft and patient survival after kidney transplantation have produced conflicting
      results. Therefore, we studied the effects of pre-transplant dialysis modality on
      outcomes in a large United States cohort. METHODS: We compared rates of
      transplantation between peritoneal dialysis and hemodialysis patients from the
      years 1995 to 1998 in the United States (N = 252,402) and outcomes after
      transplantation (N = 22,776), using data from the Centers for Medicare and
      Medicaid Services. RESULTS: In a Cox proportional hazards analysis that was
      adjusted for multiple patient characteristics, kidney transplantation was 1.39
      (95% CI = 1.35 to 1.43) times more likely in peritoneal dialysis vs. hemodialysis
      patients (P < 0.0001). Over the entire follow-up period, the adjusted risk for
      death-censored graft failure was 1.15 (1.04 to 1.26) times higher in peritoneal
      dialysis vs. hemodialysis (P < 0.05), but mortality and overall graft failure
      rates were not different. Pre-transplant dialysis modality did not affect
      outcomes for patients who survived with a functioning kidney for at least 3
      months. However, in adjusted Cox analyses restricted to the first 3 months,
      peritoneal dialysis was associated with a 1.23 (1.09 to 1.39) times higher risk
      for early graft failure (P < 0.001) and a 1.33 (1.16 to 1.53) times higher risk
      for death-censored graft failure (P < 0.001). Peritoneal dialysis patients,
      however, were seen to have a lower incidence of delayed graft function. In a
      smaller sample of patients with data on causes of early graft failure, graft
      thrombosis was more commonly listed as a cause of graft failure among peritoneal
      dialysis patients, 41% (64/156), compared to hemodialysis patients, 30%
      (106/349), P < 0.05. CONCLUSIONS: Kidney transplantation is more frequent in
      peritoneal dialysis than in hemodialysis patients, and transplantation in
      peritoneal dialysis patients is more frequently associated with early, but not
      late, graft failure. Delayed graft function was less common in peritoneal
      dialysis patients but this potential benefit appears to be offset by other
      factors which are associated with early graft loss. Additional studies are needed
      to determine what factors may help understand this early risk of graft failure.

PMID- 12234316
TI  - Expression of aquaporin-3 in human peritoneal mesothelial cells and its up
      regulation by glucose in vitro.
AB  - BACKGROUND: Aquaporin-3 (AQP3) is a member of the water channel family that is
      selective for the passage of not only water, but also glycerol and urea. Our
      recent study demonstrated the presence of aquaporin-1 in human peritoneal
      mesothelial cells (HPMC). Although transcripts encoding for AQP3 has been
      detected by reverse transcription-polymerase chain reaction (RT-PCR) in murine
      peritoneal mesothelium, to date there is no documentation of protein expression
      on peritoneal mesothelial cells. METHOD: Our present study was designed to
      explore the gene and protein expression of AQP3 in HPMC and its regulation under
      different concentrations of glucose. RESULTS: AQP3 protein was detected in the
      human peritoneal tissue by immunohistological staining using specific, affinity
      purified polyclonal anti-AQP3 antibodies. AQ3 transcripts and protein expression
      in cultured HPMC were investigated by RT-PCR and immunoblotting analysis
      respectively. Cell permeability to glycerol (flux) was measured using
      [(14)C]glycerol incorporation. AQP3 transcript and protein were weakly expressed
      in HPMC constitutively. The gene expression of AQP3 and its protein biosynthesis
      in HPMC were inducible following exposure to glucose in a dose- and time
      dependent manner (P < 0.0001). Glucose at a concentration of 200 mmol induced
      glycerol flux by 4.82-fold above the control value (P < 0.0001) and its effect
      was significantly inhibited by mercuric chloride (P < 0.01). CONCLUSION: Our
      novel observation demonstrated the AQP3 expression and biosynthesis in HPMC and
      in vitro studies revealed that glycerol permeability in HPMC was up-regulated by
      glucose. Further study is warranted to elucidate the role of AQP3 in HPMC for
      maintaining the ultrafiltration of the peritoneal membrane.

PMID- 12234317
TI  - Patient survival after renal transplantation: IV. Impact of post-transplant
      diabetes.
AB  - BACKGROUND: The development of de novo diabetes mellitus is a serious
      complication of kidney transplantation. This study examined the cardiovascular
      risk profile of patients with post-transplant diabetes (PTDM) and assessed the
      impact of PTDM on patient survival. METHODS: This analysis included 1811 adult,
      renal allograft recipients, transplanted in a single institution between 1983 and
      1998. Patient survival was analyzed by univariable and multivariable Cox
      regression considering PTDM as a time dependent variable. RESULTS: After a follow
      up period of 8.3 +/- 4.5 years, 293 patients (20%) developed PTDM, 14% lost their
      graft, and 20% died. Compared to patients without DM (NoDM, N = 1186) patients
      with PTDM were significantly older (40 +/- 14 vs. 48 +/- 12 years, P < 0.001),
      heavier (76 +/- 23 vs. 86 +/- 25 kg, P < 0.001), and included more African
      Americans (18 vs. 28%, P = 0.001). In addition, the incidence of PTDM was
      significantly higher in patients who were transplanted after 1995 than prior to
      that year. In contrast, there were no significant differences between PTDM and
      patients who had DM before the transplant (DM; N = 332). Compared to NoDM,
      patients with PTDM had significantly higher total serum cholesterol and
      triglycerides (TG), higher systolic blood pressure and higher pulse pressure
      throughout the post-transplant period. Of interest, all of these abnormalities
      preceded the development of PTDM. Hypertriglyceridemia was particularly
      pronounced in PTDM and elevated TG levels correlated with the subsequent
      development of PTDM, independent of other risk factors (P = 0.001 by multivariate
      Cox). Compared to NoDM (16% mortality) a significantly higher percent of DM (31%,
      P < 0.001) and PTDM (22%, P = 0.005) patients died. By Cox regression, PTDM
      correlated with reduced patient survival (hazard ratio = 1.80, CI 1.35 to 2.41, P
      = 0.001), and that relationship was independent of other correlates of reduced
      survival that included: increasing age; transplant year; reduced serum albumin;
      and male sex. CONCLUSION: s: PTDM is associated with an unfavorable
      cardiovascular risk profile that precedes the development of hyperglycemia. PTDM
      is an independent predictor of reduced survival in renal allograft recipients.

PMID- 12234318
TI  - Heat sterilization of peritoneal dialysis solutions influences ingestive behavior
      in non-uremic rats.
AB  - BACKGROUND: The appetite inhibitory effect of glucose-based peritoneal dialysis
      (PD) solutions may be due to glucose as such, or the hyperosmolality of the PD
      solution, or an effect of glucose degradation products (GDPs) formed in the PD
      solution during heat sterilization. This was studied in an experimental appetite
      model in rat. METHODS: The effect of different experimental PD solutions on
      ingestive behavior was investigated in non-uremic rats equipped with an implanted
      intraoral (i.o.) cannula through which a 1 mol/L sucrose solution was infused
      during tests. The amount of intake was recorded at 30 min after rats were infused
      intraperitoneally (IP) with 30 mL of different solutions. This method allowed an
      accurate and reproducible analysis of i.o. intake. The experimental PD solutions
      tested included (1) glucose based PD solutions with different glucose
      concentrations, sterilized by heat or microbiological filter, (2) glucose- and
      mannitol-based PD solutions with the same osmolality, sterilized by heat or
      microbiological filter; and (3) glucose based PD solutions, using different pH
      values (pH 3.0, pH 5.5 or pH 7.4) during heat sterilization. RESULTS: Following
      IP infusion of solutions, (1) the i.o. intake was significantly inhibited by
      glucose based, heat sterilized PD solutions and the degree of appetite
      suppression was related to the concentration of dialysate glucose in a dose
      dependent way; (2) the i.o. intake was significantly less suppressed by filter
      sterilized than by heat sterilized glucose-based solutions; (3) the i.o. intake
      was significantly less following the IP infusion of glucose-based than following
      the mannitol-based heat sterilized solutions; however, i.o. intake did not differ
      between the glucose-based and mannitol-based filter sterilized solutions; and (4)
      furthermore, the degree of suppression of i.o. intake induced by glucose-based PD
      solutions was influenced by the pH value during heat sterilization. The lower the
      pH of the PD solution during heat sterilization, the higher the i.o. intake.
      CONCLUSIONS: The IP infusion of glucose-based heat-sterilized PD solutions
      inhibited food intake in this experimental appetite model, and the degree of
      suppression depended on the concentration of dialysate glucose and the pH of the
      solution during heat sterilization. The results suggest that GDPs formed during
      heat sterilization may exert a more adverse effect than glucose itself on
      ingestive behavior, and that a reduction of the concentration of GDPs in the PD
      solution using filter sterilization or a low pH value in the PD solution during
      heat sterilization may improve food intake.

PMID- 12234319
TI  - Better long-term functional adaptation to the child's size with pediatric
      compared to adult kidney donors.
AB  - BACKGROUND: Pros and cons for pediatric kidney donors have been debated,
      especially with respect to survival rates. However, the effect of donor age on
      kidney function remains conflicting. The aim of this study was to compare short
      and long-term renal function according to the age of the donor, in grafts from
      adult living related (LRD), adult cadaveric and pediatric cadaveric donors
      (PedCD) following pediatric transplantation (Tx). METHODS: One hundred and thirty
      four children were repeatedly followed for four years, and 44 were followed for
      eight years. Absolute and relative glomerular filtration rate (GFR; inulin
      clearance, mL/min and mL/min/1.73 m(2), respectively) were determined within 6
      months, and yearly thereafter. RESULTS: Absolute GFR increased along with body
      growth in the PedCD group (P < 0.001) during the 4 years following Tx, leading to
      stable relative GFR, whereas absolute GFR of the LRD group did not change, with a
      progressive decrease of relative GFR (P < 0.001). Relative GFR did not differ
      between PedCD and LRD recipients by the sixth month but became higher in PedCD 4
      years post-Tx (70 +/- 25 vs 52 +/- 19 mL/min/1.73 m(2), P < 0.001). Among those
      followed for 8 years, relative GFR showed a slow decrease in both recipient
      groups from 6 years post-Tx. At 8 years post-Tx, relative GFR was still
      significantly higher in PedCD than in LRD (57 +/- 19 vs. 45 +/- 19; P < 0.05).
      CONCLUSIONS: Adult-sized grafts may adapt to pediatric recipients during the
      first months post-Tx, but graft function cannot improve thereafter along with the
      increase in body size of the recipient. Interestingly, the absolute GFR of
      children receiving pediatric grafts increased along with body growth, leading to
      a stable relative GFR up to 6 years post-Tx.

PMID- 12234320
TI  - Proteomic analysis of normal human urinary proteins isolated by acetone
      precipitation or ultracentrifugation.
AB  - BACKGROUND: Proteomic techniques have recently become available for large-scale
      protein analysis. The utility of these techniques in identification of urinary
      proteins is poorly defined. We constructed a proteome map of normal human urine
      as a reference protein database by using two differential fractionated techniques
      to isolate the proteins. METHODS: Proteins were isolated from urine obtained from
      normal human volunteers by acetone precipitation or ultracentrifugation,
      separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and
      identified by matrix-assisted laser desorption ionization-time-of-flight (MALDI
      TOF) mass spectrometry followed by peptide mass fingerprinting. RESULTS: A total
      of 67 protein forms of 47 unique proteins were identified, including
      transporters, adhesion molecules, complement, chaperones, receptors, enzymes,
      serpins, cell signaling proteins and matrix proteins. Acetone precipitated more
      acidic and hydrophilic proteins, whereas ultracentrifugation fractionated more
      basic, hydrophobic, and membrane proteins. Bioinformatic analysis predicted
      glycosylation to be the most common explanation for multiple forms of the same
      protein. CONCLUSIONS: Combining two differential isolation techniques magnified
      protein identification from human urine. Proteomic analysis of urinary proteins
      is a promising tool to study renal physiology and pathophysiology and to
      determine biomarkers of renal disease.

PMID- 12234321
TI  - The kidney proteome: a hint of things to come.

PMID- 12234322
TI  - Nodular parathyroid growth: role of vitamin D resistance.

PMID- 12234323
TI  - Renal insufficiency and the risk of cardiovascular mortality.

PMID- 12234325
TI  - Mycophenolate mofetil treatment for primary glomerular diseases.

PMID- 12234326
TI  - Hemodialysis vascular access in incident patients in Spain.

PMID- 12234328
TI  - Fetal and neonatal renal aspects of cyclooxygenase (COX) inhibition.

PMID- 12234330
TI  - The development of hypertension in acute and chronic renoparenchymal diseases.

PMID- 12234332
TI  - The effect of vitamin A on the course of infective and non-infective renal
      inflammation.

PMID- 12234333
TI  - Progressive renal and cardiovascular disease: optimal treatment strategies.

PMID- 12234334
TI  - Clustering of Saccharomyces boulardii strains within the species S. cerevisiae
      using molecular typing techniques.
AB  - AIMS: This study was undertaken to characterize and differentiate therapeutically
      relevant Saccharomyces yeasts. Among the isolates were so-called Saccharomyces
      boulardii strains, which are considered as probiotic agents, but whose taxonomic
      assignment is controversial. Moreover, the discriminative power of the applied
      molecular typing techniques should be evaluated. METHODS AND RESULTS: Genotyping
      was performed using species-specific polymerase chain reaction (PCR), randomly
      amplified polymorphic DNA-PCR, restriction fragment length polymorphism analysis
      of rDNA spacer regions and pulsed-field gel electrophoresis. Species-specific PCR
      assigned all of the product isolates to the species S. cerevisiae. By combining
      the other techniques, all isolates could be discriminated. Moreover, it could be
      demonstrated that probiotic S. boulardii strains form a separate cluster located
      within the species. CONCLUSIONS: With the exception of species-specific PCR, all
      of the applied methodologies were suitable for subspecies typing and indicated a
      close relationship between the probiotic strains. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The methods applied in this study are considered powerful tools for
      quality control of therapeutically relevant yeasts. It is of crucial importance,
      especially regarding S. boulardii yeasts, to verify the identity of the correct
      strain, since the beneficial properties are considered to be strain-specific.

PMID- 12234335
TI  - Phenotypic and molecular characterization of chickpea rhizobia isolated from
      different areas of Morocco.
AB  - AIMS: To determine the biodiversity of rhizobial strains nodulating Cicer
      arietinum L. in representative soils from various areas of Morocco. METHODS AND
      RESULTS: Symbiotic traits, utilization of 49 carbohydrate sources, resistance to
      antibiotics and heavy metals, tolerance to salinity, to extreme temperatures and
      pH were studied as phenotypic markers. In addition, restriction fragment length
      polymorphism (RFLP) of PCR-amplified 16S rDNAs were compared with those of
      reference strains. Numerical analysis of the phenotypic characteristics showed
      that the 48 strains studied fell into three distinct groups. RFLP analysis of 16S
      rRNA genes revealed an additional heterogeneity and four ribotypes were
      identified. CONCLUSIONS: Chickpea rhizobia isolated from Moroccan soils are both
      phenotypically and genetically diverse. Most of these rhizobia belong to the
      Mesorhizobium genus. However, some strains originating from a particular soil
      appeared to have 16S rRNA genes similar to Sinorhizobium as well as very distinct
      auxanographic characteristics compared with Mesorhizo- bium isolates.
      SIGNIFICANCE AND IMPACT OF THE STUDY: A well characterized collection of chickpea
      nodulating rhizobia in representative soils of Morocco has been generated, which
      can be used to develop efficient inoculants for this crop. This is the first
      report evidencing that chickpeas may be nodulated by bacteria from the
      Sinorhizobium genus.

PMID- 12234336
TI  - The prevalence and number of Salmonella in sausages and their destruction by
      frying, grilling or barbecuing.
AB  - AIMS: To determine the prevalence and number of Salmonella and Campylobacter in
      sausages and to evaluate their destruction during cooking. METHODS AND RESULTS:
      One hundred and sixty-two packs of uncooked economy or catering sausages,
      comprising 53 packs of frozen and 109 of chilled sausages, were purchased in
      Devon between March and July 2000. All were tested for the presence of Salmonella
      and 51 packs of chilled sausages were also examined for the presence of
      Campylobacter spp. To investigate the heat tolerance of Salmonella enterica
      serovar Typhimurium DT104 in sausage-meat, chilled, handmade and frozen sausages
      were inoculated with approx. 1.5 x 10(4) bacterial cells per sausage
      (approximately 300 cfu g(-1)) and then cooked by frying, grilling or barbecuing.
      The levels of creatinine kinase, lactate dehydrogenase and alkaline phosphatase
      in uncooked and cooked sausages were measured to evaluate their potential as
      indicators of adequate cooking and, therefore, pathogen elimination. Salmonella
      were detected in 7.5% of frozen and 9.1% of the chilled sausages (8.6% overall)
      but Campylobacter spp. were not isolated. After cooking, a visual assessment
      suggested that all of the sausages were thoroughly cooked. Despite this,
      barbecuing and frying sometimes allowed Salmonella cells to survive and the
      temperature profiles during cooking indicated that the lethal range was sometimes
      not reached. The enzyme levels tested were not reliable indicators of the
      inactivation of bacterial pathogens because Salmonella were sometimes isolated
      from sausages with low values of all three enzymes. CONCLUSIONS: Salmonella spp.
      are present in a significant proportion of sausages and are not always killed
      during the cooking process. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings
      have clear implications for public health.

PMID- 12234337
TI  - Development of an enzyme assay for rapid assessment of Escherichia coli in
      seawaters.
AB  - AIMS: An analytical protocol has been developed and applied for the detection of
      glucuronidase activity in marine waters as a rapid alternative approach to assess
      the microbiological quality of seawaters. METHODS AND RESULTS: The fluorogenic
      substrate 4-methylumbelliferyl-beta-D-glucuronide is cleaved to a fluorescent
      product, methylumbelliferone, by the enzyme beta-glucuronidase, specific to
      Escherichia coli and closely related enterobacterial species (Shigella). The
      results suggest that this test is related to E. coli numbers, as estimated by
      immunofluorescence, more significantly than to faecal coliform numbers, obtained
      from culture media. CONCLUSIONS: The determination of the potential rate of
      glucuronidase activity may be used as a diagnostic tool for the indirect
      estimation of the presence of E. coli in seawaters. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The method may be particularly useful in the early warning of seawater
      pollution, allowing the screening of coastal areas with different contamination
      levels in reduced time.

PMID- 12234338
TI  - Enumeration of faecal coliforms from recreational coastal sites: evaluation of
      techniques for the separation of bacteria from sediments.
AB  - AIMS: To identify the most efficient techniques for the separation of micro
      organisms from coastal sediments and, using these techniques, to determine the
      concentration of faecal indicator organisms in recreational coastal water and
      sediment. METHODS AND RESULTS: Sediment samples were taken from a range of
      recreational coastal sites and subjected to various physical techniques to
      separate micro-organisms from sediment particles. Techniques investigated
      included manual shaking, treatment by sonication bath for 6 and 10 min,
      respectively, and by sonication probe for 15 s and 1 min, respectively. The use
      of the sonication bath for 10 min was the most successful method for removing
      micro-organisms from sediment particles where sediments consisted mainly of sand.
      When sediments contained considerable proportions of silt and clay, however,
      manual shaking was most successful. Faecal coliforms were then enumerated by
      membrane filtration in both water and sediment from three recreational coastal
      sites, chosen to represent different physical sediment characteristics, over a 12
      month period. Faecal coliform concentrations were generally greater in sediment
      compared with overlying water for all samples. This was most evident in sediment
      consisting of greater silt/clay and organic carbon content. CONCLUSIONS: This
      study demonstrated the importance of sediment characteristics in determining the
      most efficient method for the separation of micro-organisms from coastal
      sediments. Sediment characteristics were also found to influence the persistence
      of micro-organisms in coastal areas. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Recreational coastal sediments can act as a reservoir for faecal coliforms;
      therefore, sampling only overlying water may greatly underestimate the risk of
      exposure to potentially pathogenic micro-organisms in recreational waters.

PMID- 12234339
TI  - Antifungal activities of two Lactobacillus plantarum strains against Fusarium
      moulds in vitro and in malting of barley.
AB  - AIMS: The Lactobacillus plantarum strains VTT E-78076 (E76) and VTT E-79098 (E98)
      were studied for their antifungal potential against Fusarium species. METHODS AND
      RESULTS: In vitro screening with automated turbidometry as well as direct and
      indirect impedimetric methods clearly showed Lact. plantarum cell-free extracts
      to be effective against Fusarium species including Fusarium avenaceum, F.
      culmorum, F. graminearum and F.oxysporum. However, great variation in growth
      inhibition was observed between different Fusarium species and even between
      strains. The antifungal potential of Lact. plantarum E76 culture, including cells
      and spent medium, was also examined in laboratory-scale malting with naturally
      contaminated two-rowed barley from the crops of 1990-96. The growth of the
      indigenous Fusarium flora was restricted by the addition of Lact. plantarum E76
      to the steeping water. However, the antifungal effect was greatly dependent on
      the contamination level and the fungal species/strains present on barley in
      different years. CONCLUSIONS: Lactobacillus plantarum strains E76 and E98 had a
      fungistatic effect against different plant pathogenic, toxigenic and gushing
      active Fusarium fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study
      indicates that Lact. plantarum strains with known and selected characteristics
      could be used as a natural, food-grade biocontrol agent for management of
      problems caused by Fusarium fungi during germination of cereals.

PMID- 12234340
TI  - Diversity among Bradyrhizobium isolates nodulating yardlong bean and sunnhemp in
      Guam.
AB  - AIMS: To isolate and characterize bradyrhizobia that nodulate yardlong bean and
      sunnhemp in Guam. METHODS AND RESULTS: Bradyrhizobia populations that nodulate
      yardlong bean and sunnhemp in Guam were examined for genetic diversity and their
      relatedness to Bradyrhizobium japonicum and B. elkanii reference strains. Genomic
      DNA of 58 isolates of Bradyrhizobium spp. was hybridized with B. japonicum nodY
      and B. elkanii nodK genes. Based on the hybridization patterns, the isolates were
      classified into three nodY-nodK hybridizing groups. Group I comprised the
      majority of the isolates and hybridized with nodY whereas group II isolates
      hybridized with nodK. The group III isolates, that did not hybridize with either
      nodY or nodK, formed nitrogen-fixing nodules on cowpea but did not nodulate
      soybean. DNA sequence analysis of a 280-bp fragment of the variable region of the
      16S rRNA gene of a few group III isolates showed that these isolates were more
      similar to Bradyrhizobium spp. than to B. japonicum or B. elkanii. CONCLUSIONS:
      The majority of the isolates nodulating yardlong bean and sunnhemp in Guam are
      similar to B. japonicum, although some isolates are similar to Bradyrhizobium
      spp. that nodulate a miscellaneous group of legumes including cowpea.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Since both yardlong bean and sunnhemp are
      nodulated by a range of bradyrhizobia, selection of superior strains may be based
      on nodulation effectiveness on both legumes.

PMID- 12234341
TI  - Comparative surface-to-hand and fingertip-to-mouth transfer efficiency of gram
      positive bacteria, gram-negative bacteria, and phage.
AB  - AIMS: To determine the transfer efficiency of micro-organisms from fomites to
      hands and the subsequent transfer from the fingertip to the lip. METHODS AND
      RESULTS: Volunteers hands were sampled after the normal usage of fomites seeded
      with a pooled culture of a Gram-positive bacterium (Micrococcus luteus), a Gram
      negative bacterium (Serratia rubidea) and phage PRD-1 (Period A). Activities
      included wringing out a dishcloth/sponge, turning on/off a kitchen faucet,
      cutting up a carrot, making hamburger patties, holding a phone receiver, and
      removing laundry from the washing machine. Transfer efficiencies were 38.47% to
      65.80% and 27.59% to 40.03% for the phone receiver and faucet, respectively.
      Transfer efficiencies from porous fomites were <0.01%. In most cases, M.luteus
      was transferred most efficiently, followed by phage PRD-1 and S. rubidea. When
      the volunteers' fingertips were inoculated with the pooled organisms and held to
      the lip area (Period B), transfer rates of 40.99%, 33.97%, and 33.90% occurred
      with M. luteus, S. rubidea, and PRD-1, respectively. CONCLUSIONS: The highest
      bacteral transfer rates from fomites to the hands were seen with the hard, non
      porous surfaces. Even with low transfer rates, the numbers of bacteria
      transferred to the hands were still high (up to 10(6) cells). Transfer of
      bacteria from the fingertip to the lip is similar to that observed from hard
      surfaces to hands. SIGNIFICANCE AND IMPACT OF THE STUDY: Infectious doses of
      pathogens may be transferred to the mouth after handling an everyday contaminated
      household object.

PMID- 12234342
TI  - A comparison between broiler chicken carcasses with and without visible faecal
      contamination during the slaughtering process on hazard identification of
      Salmonella spp.
AB  - AIMS: A comparison of the prevalence of Salmonella in chicken carcasses with and
      without visible faecal contamination during commercial slaughter practice was
      made. The relationship between Enterobacteriaceae, coliform and Escherichia coli
      counts and Salmonella status was also evaluated to establish the likelihood of
      using these groups as 'index' organisms to predict the presence of pathogen.
      METHODS AND RESULTS: Samples were removed immediately after evisceration, after
      the inside-outside shower and after chilling from the processing line for
      microbiological analysis. Of the carcasses visibly uncontaminated with faeces
      after the evisceration step 20% harboured salmonellas and 20.8% of the visibly
      contaminated carcasses were positive for the pathogen. When E. coli, coliforms
      and Enterobacteriaceae were used as predictor variables the error rates ranged
      from 33.3 to 60% for both sample types. CONCLUSIONS: There was no indication that
      any of the groups of organisms analysed could predict the incidence of
      salmonellas on the samples studied. Positive results for the pathogen were
      obtained at every tested step of the slaughtering process regardless of whether
      or not faecal contamination was present. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The present study demonstrated that carcasses not visibly contaminated with
      faeces carried Salmonella as well as the visibly contaminated carcasses.

PMID- 12234343
TI  - Application of laser scanning cytometry followed by epifluorescent and
      differential interference contrast microscopy for the detection and enumeration
      of Cryptosporidium and Giardia in raw and potable waters.
AB  - AIMS: The main goal of this study was to validate a new laser scanning cytometry
      method (ChemScanRDI) that couples immunofluorescence detection with differential
      interference contrast (DIC) confirmation, against manual microscopic enumeration
      of Giardia and Cryptosporidium (oo)cysts. This study also assessed the basic
      performance of the new Association Francaise de Normalisation (AFNOR) NF T 90-455
      method for Giardia and Cryptosporidium (oo)cyst enumeration with respect to
      (oo)cyst yield, linearity, repeatability, influence of turbidity and detection
      limit in raw and potable waters. METHODS AND RESULTS: The new standard method
      relies on cartridge (Envirocheck) filtration, immunomagnetic separation
      purification, immunofluorescence staining and detection followed by DIC
      confirmation. The recovery was 30-50% for both parasites at seeding levels from
      30 to 230 (oo)cysts. The method is linear from 0 to around 400 seeded (oo)cysts
      and the yield does not significantly vary for turbidity levels from 10 to 40
      Formazin Nephelometric Units (FNU). The results were obtained using manual
      microscopic enumeration of the (oo)cysts. The ChemScanRDI yielded counts that
      were at least equivalent to those obtained using manual microscopy for both
      parasites in raw and potable water concentrates, for seeding levels of 10-300 or
      10-100, respectively. The purification and labelling method proposed by the
      supplier of theChemScanRDI (Chemunex) reached very similar recoveries to the
      AFNOR protocol (70-86% in both cases). CONCLUSIONS: Laser scanning cytometry can
      be used as a more standardized alternative to manual enumeration as part of the
      new AFNOR standard method. SIGNIFICANCE AND IMPACT OF THE STUDY: By using laser
      scanning cytometry instead of manual microscopy, laboratories could circumvent
      the limitations of manual microscopy, namely: low sample throughput, operator
      subjectivity and operator fatigue. The study further supports the drive to
      incorporate laser scanning cytometry in the standard methods for Giardia and
      Cryptosporidium enumeration.

PMID- 12234344
TI  - Saccharomyces cerevisiae wine yeast populations in a cold region in Argentinean
      Patagonia. A study at different fermentation scales.
AB  - AIMS: To study the diversity and dynamics of indigenous Saccharomyces wine
      populations during Malbec spontaneous fermentation, a representative Patagonian
      red wine, at both industrial and laboratory scale. METHODS AND RESULTS: Two
      molecular techniques, including restriction fragment length polymorphism of
      mitochondrial (mt) DNA and polymorphism of amplified delta interspersed element
      sequences, were used for characterization of indigenous yeasts at strain level.
      The mtDNA restriction patterns showed the major discriminative power; however, by
      combining the two molecular approaches it was possible to distinguish a larger
      number of strains and, therefore, draw more representative conclusions about
      yeast diversity. Although a great diversity of wild Saccharomyces cerevisiae
      strains was observed, only nine represented more than half of the total
      Saccharomyces yeast biota analysed; five of these were common and took over the
      Malbec must fermentation in both vinifications. CONCLUSIONS: Many different
      indigenous S. cerevisiae strains were identified; nevertheless, the dominant
      strains in both industrial and laboratory vinification processes were just a few
      and the same. SIGNIFICANCE AND IMPACT OF THE STUDY: Small-scale fermentation
      appears to be a valuable tool in winemaking, one especially helpful in evaluating
      microbiological aspects of as well as possible interactions between inoculated
      selected strains and native strains.

PMID- 12234345
TI  - Diversity of Burkholderia isolates from woodland rhizosphere environments.
AB  - AIMS: Determination of genetic diversity among UK Burkholderia cepacia isolates
      from various environmental niches, principally woodland tree rhizospheres and
      onions. METHODS AND RESULTS: Genus determination was made using polymerase chain
      reaction (PCR) amplification and fatty acid methyl ester profiling. Genetic
      diversity was investigated by repetitive sequence genetic PCR fingerprinting.
      Several onion isolates were similar to clinical isolates but others were diverse.
      Some environmental isolates were possibly synonymous with B. cepacia and B.
      gladioli but most from woodland rhizospheres were distinct and clustered
      together. The 16S rRNA genes of representatives from these clusters were PCR
      amplified, sequenced and phylogenetically compared with all known Burkholderia
      and related species. This revealed that the rhizospheric isolates had closest
      affinity with Burkholderia spp. with known bioremediative and biocontrol
      capabilities and were unrelated to taxa comprising plant or human pathogenic
      strains. CONCLUSIONS: All of the analyses investigated revealed that
      environmental and onion isolates of B. cepacia complex bacteria are genetically
      diverse but that woodland rhizospheric isolates are related to each other and
      unrelated to plant or human pathogenic strains. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Woodland rhizospheric isolates of B. cepacia are potentially good
      candidates for use in bioremediation and biocontrol, as they appear distinct from
      plant or human pathogenic strains.

PMID- 12234346
TI  - Isolation and characterization of a mutant strain of Streptococcus uberis, which
      fails to utilize a plasmin derived beta-casein peptide for the acquisition of
      methionine.
AB  - AIMS: To isolate and characterize a mutant of Streptococcus uberis strain 0140J
      which fails to utilize a plasmin derived beta-casein peptide for the acquisition
      of methionine. METHODS AND RESULTS: Random insertional mutagenesis was used to
      isolate a mutant strain of Strep. uberis 0140J which was unable to utilize
      methionine from within a casein-derived peptide. The altered gene in the mutant
      strain showed homology to an oligopeptide permease gene of Streptococcus pyogenes
      (oppF). The mutant was unable to obtain specific amino acids from defined
      peptides of various lengths and its growth yield in skimmed milk was between 1
      and 10% that of the wild-type strain, but was restored following the inclusion of
      these amino acids. CONCLUSIONS: The oligopeptide permease homologue of Strep.
      uberis 0140J is necessary for the utilization of amino acids from within specific
      peptides. Efficient acquisition of essential amino acids by Strep. uberis 0140J
      is required for the bacterium to achieve an optimum yield in milk. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Streptococcus uberis is a major agent of bovine mastitis
      with a corresponding high economic loss. By targeting metabolic pathways
      essential to the growth of Strep. uberis it may be possible to prevent the
      establishment of growth of the bacterium in milk. This study has identified the
      acquisition of essential amino acids as playing a role in the growth of Strep.
      uberis in milk.

PMID- 12234347
TI  - Bacteriology of the Labrador dog gut: a cultural and genotypic approach.
AB  - AIMS: To carry out an extensive study of the microflora composition of the
      Labrador dog gut. METHODS AND RESULTS: Faecal specimens from four Labradors were
      collected and plated onto growth media designed to recover total anaerobes,
      bacteroides, bifidobacteria, lactobacilli, clostridia, Gram-positive cocci, total
      aerobes and coliforms. Morphologically different isolates were collected from all
      agars inoculated with faeces from one canine individual (repeated four times). A
      total of 157 out of 171 isolates were identified using 16S rRNA gene sequencing.
      Sequence analysis showed that agar selectivity was poor, especially when
      bacteroides and Gram-positive cocci were the targets. Bifidobacteria were not
      detected in any of the samples analysed, indicating their presence at low or
      negligible levels. The gene sequences of many of the isolates (n=45, representing
      29% of the total) did not correlate with known species in the Ribosomal Database
      Project and EMBL databases, suggesting the presence of novel gut diversity.
      CONCLUSIONS: Traditional culture methods fail to reflect the bacterial diversity
      present in Labrador dog faeces. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      has shown the value of molecular-based methodologies for determining bacterial
      profiles in the Labrador dog gut microbiota, but has also exposed the limitations
      of purportedly selective agars.

PMID- 12234348
TI  - Amplification of RNA by NASBA allows direct detection of viable cells of
      Ralstonia solanacearum in potato.
AB  - AIMS: The objective of this study was to develop a Nucleic Acid Sequence Based
      Amplification (NASBA) assay, targeting 16S rRNA sequences, for direct detection
      of viable cells of Ralstonia solanacearum, the causal organism of bacterial wilt.
      The presence of intact 16S rRNA is considered to be a useful indicator for
      viability, as a rapid degradation of this target molecule is found upon cell
      death. METHODS AND RESULTS: It was demonstrated by RNase treatment of extracted
      nucleic acids from R. solanacearum cell suspensions that NASBA exclusively
      detected RNA and not DNA. The ability of NASBA to assess viability was
      demonstrated in two sets of experiments. In the first experiment, viable and
      chlorine-killed cells of R. solanacearum were added to a potato tuber extract and
      tested in NASBA and PCR. In NASBA, only extracts spiked with viable cells
      resulted in a specific signal after Northern blot analysis, whereas in PCR,
      targeting 16S rDNA sequences, both extracts with viable and killed cells resulted
      in specific signals. In the second experiment, the survival of R. solanacearum on
      metal strips was studied using NASBA, PCR-amplification and dilution plating on
      the semiselective medium SMSA. A positive correlation was found between NASBA and
      dilution plating detecting culturable cells, whereas PCR-amplification resulted
      in positive reactions also long after cells were dead. The detection level of
      NASBA for R. solanacearum added to potato tuber extracts was determined at 104
      cfu per ml of extract, equivalent to 100 cfu per reaction. With purified RNA a
      detection level of 104 rRNA molecules was found. This corresponds with less than
      one bacterial cell, assuming that a metabolically active cell contains ca 105
      copies of rRNA. Preliminary experiments demonstrated the potential of NASBA to
      detect R. solanacearum in naturally infected potato tuber extracts. CONCLUSIONS:
      NASBA specifically amplifies RNA from viable cells of R. solanacearum even
      present in complex substrates at a level of 100 cfu per reaction. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The novel NASBA assay will be particularly valuable for
      detection of R. solanacearum in ecological studies in which specifically viable
      cells should be determined.

PMID- 12234349
TI  - An arsenic(III)-oxidizing bacterial population: selection, characterization, and
      performance in reactors.
AB  - AIMS: To select an autotrophic arsenic(III)-oxidizing population, named CASO1,
      and to evaluate the performance of the selected bacteria in reactors. METHODS AND
      RESULTS: An As(III)-containing medium without organic substrate was used to
      select CASO1 from a mining environment. As(III) oxidation was studied under batch
      and continuous conditions. The main organisms present in CASO1 were identified
      with molecular biology tools. CASO1 exhibited significant As(III)-oxidizing
      activity between pH 3 and 8. The optimum temperature was 25 degrees C. As(III)
      oxidation was still observed in the presence of 1000 mg l(-1) As(III). In
      continuous culture mode, the As(III) oxidation rate reached 160 mg l(-1) h(-1).
      The CASO1 consortium contains at least two organisms - strain b3, which is
      phylogenetically close to Ralstonia picketii, and strain b6, which is related to
      the genus Thiomonas. The divergence in 16S rDNA sequences between b6 and the
      closest related organism was 5.9%, suggesting that b6 may be a new species.
      CONCLUSIONS: High As(III)-oxidizing activity can be obtained without organic
      nutrient supply, using a bacterial population from a mining environment.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The biological oxidation of arsenite by the
      CASO1 population is of particular interest for decontamination of arsenic
      contaminated waste or groundwater.

PMID- 12234350
TI  - Culture conditions influencing phytase production of Mitsuokella jalaludinii, a
      new bacterial species from the rumen of cattle.
AB  - AIMS: The effects of pH, temperature, phytate, glucose, phosphate and surfactants
      on the phytase production of Mitsuokella jalaludinii, a new bacterial species
      from the rumen of cattle, were evaluated. METHOD AND RESULTS: By using batch
      fermentation, it was found that phytase production of M. jalaludinii was induced
      by sodium phytate. Inclusion of glucose into rice bran-soybean milk (RB-SM)
      medium inhibited the phytase production. Supplementation of 0.05-0.5% of
      phosphate to RB-SM medium neither inhibited nor stimulated the phytase
      production. The optimum pH and temperature for the phytase production of M.
      jalaludinii were 7.02 and 39 degrees C, respectively. Surfactants such as Tween
      80 (0.5% and 1.0%) and Triton X-100 (1.0%) did not affect the phytase production.
      CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: The study has provided
      important data on the culture conditions affecting phytase production of M.
      jalaludinii, which will facilitate future research on the optimization of
      fermentation processes for production of high phytase activity by M. jalaludinii.

PMID- 12234351
TI  - PCR detection of potentially pathogenic aeromonads in raw and cold-smoked
      freshwater fish.
AB  - AIMS: Development of a PCR assay for detection of aeromonads carrying the hlyA
      and/or aerA genes in fish. METHODS AND RESULTS: The protocol involves an
      overnight selective enrichment step in tryptic soy broth yeast extract containing
      10 microg ml(-1) of ampicillin followed by extraction of DNA and PCR
      amplification of two haemolysin genes that contribute to the virulence of Aer.
      hydrophila. This procedure can detect initial populations of 1-10 cfu g(-1)
      within 24 h in artificially contaminated samples. In naturally contaminated fish,
      both genes were detected in 13 out of 14 fresh fish lots (aeromonads levels
      between < 1 and 5.42 log cfu g(-1)) and in 4 out of 16 lots of vacuum-packed cold
      smoked fish (aeromonads levels between < 1 and 3.37 log cfu g(-1)). Before
      enrichment, dominant species were Aer. hydrophila HG1 (aerA+hlyA+), Aer.
      bestiarum HG2 (aerA+hlyA+) and Aer. caviae HG4 (aerA-hlyA-). After enrichment,
      Aer. hydrophila HG1 (aerA+hlyA+) was dominant. CONCLUSIONS: Fresh fish and even
      smoked fish carry hlyA+ and/or aerA+ aeromonads that can be detected by PCR
      within 24 h. SIGNIFICANCE AND IMPACT OF THE STUDY: The PCR assay described offers
      considerable potential as a rapid method with specificity, sensitivity and
      simplicity.

PMID- 12234352
TI  - Amplified fragment length polymorphism (AFLP) and biochemical typing of
      Photobacterium damselae subsp. damselae.
AB  - AIMS: The aim of the present study was to characterize subspecifically
      Photobacterium damselae subsp. damselae strains isolated from cultured Sparus
      aurata and Dicentrarchus labrax by means of phenotypic and molecular typing
      techniques (amplified fragment length polymorphism, AFLP). METHODS AND RESULTS:
      Seventy-one strains of P. damselae subsp. damselae were isolated from 38 cultured
      fishes at different fish farms located on the Mediterranean coast near Valencia,
      Spain. Most fish studied were asymptomatic and some were recovered during
      infectious outbreaks. Phenotypic characterization revealed a considerable degree
      of variability within the subspecies, including some characters, such as
      production of urease, which are used to differentiate P. damselae subsp. damselae
      from P. damselae subsp. piscicida. Genetic characterization was conducted on a
      selection of 33 strains, including two reference strains. Dice coefficient (Sd)
      and the unweighted pair group method with average linkage (UPGMA) were used for
      numerical analysis of banding patterns. AFLP type was defined on the basis of
      100% similarity in the dendrogram obtained, yielding 24 distinct AFLP profiles.
      At 70% similarity, 13 clusters were defined, thus confirming the great
      variability observed for the phenotypic traits. CONCLUSIONS: The AFLP variability
      shown by the isolates was high enough to discriminate between different strains
      which colonize the same fish. However, closely related AFLP types were usually
      derived from strains isolated at the same fish farm, indicating an
      epidemiological relationship. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      has confirmed that the AFLP technique allows discrimination of individual strains
      within P. damselae subsp. damselae for epidemiological studies, and that this
      subspecies exhibits greater variability than that described for subspecies
      piscicida.

PMID- 12234353
TI  - Protective effects of cold temperature and surface-contact on acid tolerance of
      Salmonella spp.
AB  - AIMS: To determine the effect of cold-storage temperature and surface contact on
      the survival of Salmonella spp. during acid challenge. To determine the
      contribution of sigma transcriptional factor (encoded by rpoS) in surface contact
      mediated acid tolerance. METHODS AND RESULTS: Salmonella serovar Typhimurium
      cells in exponential and stationary growth phase were subjected to acid challenge
      in planktonic and surface-associated states. Low temperatures offered protection
      against acid challenge to cells which were in stationary growth phase (but not to
      those in exponential growth phase). The cells from stationary, as well as
      logarithmic growth phase, acquired increased acid tolerance upon surface contact
      with various surfaces, such as fresh-cut apples, agar and polyethersulphone
      membranes. The alternative sigma transcription factor was not required to acquire
      surface contact-mediated acid tolerance. CONCLUSIONS: Salmonella spp. take
      advantage of low temperature and surface association to overcome acid challenge.
      Some of the acid tolerance mechanisms are independent of the sigma transcription
      factor regulon. SIGNIFICANCE AND IMPACT OF THE STUDY: Effective control measures
      during produce processing must take into account the different susceptibilities
      of planktonic vs surface-associated food-borne pathogens.

PMID- 12234354
TI  - Ascopyrone P, a novel antibacterial derived from fungi.
AB  - AIMS: To assess the antimicrobial efficacy of ascopyrone P (APP), a secondary
      metabolite formed by the fungi Anthracobia melaloma, Plicaria anthracina, Plic.
      leiocarpa and Peziza petersi belonging to the order Pezizales. METHODS AND
      RESULTS: In vitro testing using a well diffusion procedure showed that APP at a
      high concentration (approximately 5%) inhibited the growth of Gram-positive and
      Gram-negative bacteria. Using an automated microbiology reader, growth curve
      analysis showed that 2000-4000 mg l(-1) APP caused total or significant bacterial
      inhibition after incubation for 24 h at 30 degrees C. Against certain yeast
      strains, 1000- 2000 mg l(-1) APP enhanced growth, although at higher
      concentrations inhibition of some yeasts was observed. Clostridium and fungal
      strains were not sensitive to 2000 mg l(-1) APP. No significant cidal effect was
      observed after 2 h against Listeria monocytogenes or Escherichia coli. Results
      were identical whether the APP samples tested had been produced enzymatically or
      chemically. CONCLUSIONS: At a level of 2000 mg l(-1), APP demonstrated growth
      inhibitory activity against a broad range of bacteria, but not yeasts or moulds.
      SIGNIFICANCE AND IMPACT OF THE STUDY: A possible application for this novel
      natural antimicrobial is in food preservation, to control the growth of Gram
      negative and Gram-positive bacteria in raw and cooked foods. Effective dosage
      levels would be 500-4000 mg kg(-1), depending on food type. The efficacy,
      organoleptic and safety aspects of this compound in food still need to be
      assessed.

PMID- 12234355
TI  - Survival of Escherichia coli O157:H7 in farm water: its role as a vector in the
      transmission of the organism within herds.
AB  - AIMS: The study aimed to investigate the survival characteristics of Escherichia
      coli O157:H7 in farm water (FW), and in sterile distilled municipal water (SDW),
      stored outdoors under field conditions, with or without the addition of faeces
      (1% w/v), in a farmyard shed and the laboratory at 15 degrees C. METHODS AND
      RESULTS: Water samples were inoculated with E. coli O157:H7 at 10(3) and 10(6)
      ml(-1), and sampled over a 31-day period. In FW stored outdoors in a field, E.
      coli O157:H7 survived for 14 days at temperatures <15 degrees C, at both
      inoculation levels, while in the laboratory at 15 degrees C, the organism was
      still detectable at low levels (<1 log10 cfu ml(-1)) after 31 days. The addition
      of bovine faeces to water outdoors (1% w/v) resulted in survival for 24 days. In
      SDW inoculated at 10(6) ml(-1) and stored in the laboratory (15 degrees C), only
      a 2.5 log reduction was observed after 31 days, while the organism could not be
      detected after 17 days in the field. Preliminary screening of water samples
      stored outdoors isolated a bacterium which exhibited antimicrobial activity
      towards E. coli O157:H7. CONCLUSIONS: The survival of E. coli O157:H7 observed in
      this study illustrates the potential of farm water to act as a vehicle in the
      transfer of the organism across a herd. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      difficulty in extrapolating results from controlled laboratory situations to on
      farm conditions is also highlighted in this study.

PMID- 12234356
TI  - Influence of pH, temperature and culture media on the growth and bacteriocin
      production by vaginal Lactobacillus salivarius CRL 1328.
AB  - AIMS: To study the influence of pH, temperature and culture medium on the growth
      and bacteriocin production by vaginal Lactobacillus salivarius subsp. salivarius
      CRL 1328. METHODS AND RESULTS: The study was performed using a complete factorial
      experimental design. Lactobacillus salivarius was cultivated in LAPTg and MRS
      broths, adjusted to specific initial pH, and at different temperatures of
      incubation. The growth, which was evaluated by the Gompertz model, was higher in
      MRS broth than in LAPTg broth. The initial pH of the culture medium and the
      temperature had a dramatic effect on the production of bacteriocin. The optimal
      conditions for bacteriocin production were different to those for optimal growth.
      The decrease in the pH of the culture medium was parallel to the growth; pH had
      similar final values in both the MRS and the LAPTg broths. CONCLUSIONS: The
      optimal growth conditions were recorded in MRS broth, with an initial pH of 6.5
      and a temperature of 37 degrees C. The maximum bacteriocin activity was obtained
      in LAPTg after 6 h at 37 degrees C, and at an initial pH of 6.5 or 8.0.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The application of a complete factorial
      design, and the evaluation of the growth parameters through the Gompertz model,
      enabled a rapid and simultaneous exploration of the influence of pH, temperature
      and growth medium on both growth and bacteriocin production by vaginal Lact.
      salivarius CRL 1328.

PMID- 12234358
TI  - Integration of inflammatory signals by rolling neutrophils.
AB  - In inflammation, neutrophils roll along the endothelial wall of postcapillary
      venules and sample inflammatory signals. Neutrophil activation is required to
      generate beta(2) integrin bonds with the endothelium that are strong enough to
      withstand the flow forces and thus achieve arrest from the rolling state. Unlike
      naive T cells, neutrophils are not only activated by ligation of G-protein
      coupled receptors with chemokines and other chemoattractants but also receive
      signals from engagement of adhesion molecules including the selectins and beta(2)
      integrins. Rolling neutrophils integrate the sum total of inputs received while
      scanning the inflamed endothelium. In this process, the velocity of rolling
      neutrophils systematically decreases as a function of their contact time with the
      inflamed endothelium. If an activation threshold is reached, beta(2) integrins
      switch to the high-affinity conformation, redistribute on the cell surface, and
      trigger arrest and adhesion. Rolling cells that do not reach the activation
      threshold detach from the endothelium and are released back into the circulation.
      The role of chemokines, adhesion molecules, and other activating inputs involved
      in this response as well as signaling pathways are the subjects of ongoing
      investigations. This review provides a conceptual framework for neutrophil
      recruitment from the flowing blood.

PMID- 12234359
TI  - Glycosylation in the control of selectin counter-receptor structure and function.
AB  - Leukocyte trafficking is characterized by sequential cell adhesion and activation
      events that deliver specific leukocyte subsets to distinct extravascular
      locations under different pathophysiological circumstances. E-, P- and/or L
      selectin-dependent leukocyte-endothelial cell adhesive interactions contribute
      essentially to this process. Selectin counter-receptor activity on leukocyte and
      high endothelial venules is borne by specific glycoproteins whose ability to
      support adhesion requires specific post-translational modifications. These
      modifications are typified by serine/threonine-linked oligosaccharides capped
      with the sialyl Lewis x moiety, an alpha2-3sialylated, alpha1-3ucosylated
      tetrasaccharide synthesized by specific glycosyltransferases. Recent advances in
      glycan structure analysis and in characterizing mice with targeted deletions of
      glycosyltransferase and sulfotransferase genes discloses an essential role for 6
      O GlcNAc sulfate modification of the sialyl Lewis x tetrasaccharide in L-selectin
      counter-receptor activity. Related studies identify novel extended Core 1 type O
      glycans bearing the 6-sulfosialyl Lewis x moiety, define the molecular nature of
      the MECA-79 epitope, and disclose a requirement for the alpha1
      3fucosyltransferases FucT-IV and FucT-VII in the elaboration of L-selectin
      counter-receptor activities. Parallel studies also demonstrate that these 2
      fucosyltransferases, a core 2 GlcNAc transferase, and core 2-type sialyl Lewis x
      determinants make essential contributions to leukocyte P-selectin counter
      receptor activity, and figure prominently in the control of leukocyte E-selectin
      counter-receptor activity.

PMID- 12234361
TI  - A novel adhesion pathway that regulates dendritic cell trafficking and T cell
      interactions.
AB  - Dendritic cells (DC) are present in essentially every tissue, where they operate
      at the interface of innate and acquired immunity by recognizing pathogens and
      presenting pathogen-derived peptides to T cells. Cell-cell interactions between
      DC, T cells and endothelial cells are crucial to all immunological processes.
      Recently, several C-type lectin receptors have been characterized that are
      abundantly expressed on the surface of DC. It is now becoming clear that these
      lectin receptors serve not only as antigen-receptors recognizing pathogens, but
      they may also function as adhesion receptors and/or signaling molecules. In
      particular the DC specific C-type lectin DC-SIGN (CD209) regulates adhesion
      processes, such as DC trafficking by interacting with ICAM-2 and T cell synapse
      formation, upon binding of ICAM-3. C-type lectins such as DC-SIGN contain a
      lectin domain that recognizes in a Ca2+-dependent manner carbohydrates such as
      mannose-containing structures presented on the glycoproteins ICAM-2 and ICAM-3.
      Although the integrin LFA-1 is a counter-receptor for both ICAM-2 and ICAM-3, on
      DC, DC-SIGN is the high affinity adhesion receptor for ICAM-2/-3. Here we discuss
      how the heterogeneity of mannose-residues exposed on cellular proteins and
      pathogens regulates specific binding of a repertoire of DC-expressed C-type
      lectins that contribute to the diversity of immune responses created by DC.

PMID- 12234360
TI  - Rapid leukocyte integrin activation by chemokines.
AB  - Chemokines control selective targeting of circulating leukocytes to the
      microvasculature by triggering inside-out signal transduction pathways leading to
      integrin-dependent adhesion. Integrin activation by chemokines is very rapid, is
      downmodulated within minutes and appears to involve both enhanced heterodimer
      lateral mobility on the plasma membrane, facilitating encounters with dispersed
      ligand, as well as induction of a high-affinity state. These two modalities of
      integrin activation by chemokines involve distinct signaling pathways in the
      cell, yet complement each other functionally, allowing binding of rolling cells
      under conditions of low as well as high ligand density. Recent data show that
      chemokines generate both pro- and anti-adhesive intracellular signaling events,
      whose equilibrium is likely to be relevant to the kinetics of adhesion and de
      adhesion, and to cell movement during diapedesis and chemotaxis. Importantly,
      chemokines utilize different signaling mechanisms to modulate the activity of
      distinct integrin subtypes. These recent advances suggest that chemokines may
      regulate adhesive responses of immune cells based not only on patterns of
      chemokine receptor expression, but also on variable signaling pathways that can
      modulate the pro-adhesive responses of leukocytes as a function of their
      differentiated state, and of the local microenvironment.

PMID- 12234362
TI  - The role of endothelial cell lateral junctions during leukocyte trafficking.
AB  - An essential function of the inflammatory response is selective targeting of
      appropriate leukocyte types to a site of infection or injury. The past decade has
      witnessed an explosion in the level of detail concerning the identification and
      deciphering of the molecular mechanisms that capture leukocytes from flowing
      blood and promote leukocyte arrest on the vessel wall. In contrast, less
      information is known about the migration of adherent blood leukocytes through
      endothelial cell-to-cell borders (transendothelial migration, TEM) and into the
      underlying tissues. This article reviews the endothelial-dependent mechanisms
      that coordinate TEM in peripheral vasculature and highlights the role of certain
      lateral junctional proteins and protein complexes.

PMID- 12234363
TI  - Cell adhesion and polarity during immune interactions.
AB  - Intercellular interactions are critical for a coordinated function of different
      cell types involved in the immune response. Here we review the cellular and
      molecular events occurring during cell-cell immune contacts. Cognate naive CD4+ T
      lymphocyte-dendritic cell (DC) and primed T cell-antigen-presenting B lymphocyte
      interactions are discussed. The engagement of cytotoxic T lymphocytes (CTL) or
      natural killer cells (NK) with their targets is analyzed and compared to the
      process of T cell-antigen-presenting cell (APC) conjugate formation. The
      immunological synapse, a complex cluster of molecules organized at the contact
      area of cell conjugates, exhibits common features but shows some differences
      depending on cell types involved. Cellular interactions occur in sequential
      stages that involve dramatic changes in cell polarity and dynamic redistribution
      of cell membrane receptors. The role of membrane microdomains, adaptor molecules
      and the cytoskeleton in the regulation of the molecular reorganization at cell
      cell contacts is also discussed.

PMID- 12234364
TI  - TCR triggering on the move: diversity of T-cell interactions with antigen
      presenting cells.
AB  - Polarized T cells are mobile cells optimized for migration, receptor scanning,
      and signaling. When in contact with antigen-presenting cells (APCs), polarized T
      cells can develop a spectrum of biophysical interaction modes ranging from
      adhesive sticking to dynamic crawling. Both static and dynamic contacts support
      sustained triggering of the T-cell receptor (TCR), leading to signal induction, T
      blast formation, and proliferation. In dynamic interactions, T cells crawl across
      the surface of the APC at speeds of 2-6 micro m/min and simultaneously establish
      an asymmetric tight yet mobile junction plane, representing a dynamic
      immunological synapse. In dynamic synapses three functional compartments of the
      polarized T cell are in close contact with the APC surface, i.e. leading edge,
      cell body and uropod. Through its mobility, the asymmetric junction is
      topographically suited for receptor scanning and engagement at the leading edge,
      retrograde receptor movement along the junction, and exit from the uropod. Herein
      we develop a model on scanning encounters between T cells and APCs that includes
      the simultaneous engagement of T-cell leading edge and uropod and implicates a
      serial receptor triggering mode in cell-cell recognition.

PMID- 12234365
TI  - The regulation of actin remodeling during T-cell-APC conjugate formation.
AB  - The T-cell cytoskeleton is intimately involved in determining the efficiency and
      fidelity of the immune response. During T-cell interactions with antigen
      presenting cells (APCs), dynamic remodeling of the actin cytoskeleton is
      particularly important for stabilizing long-lived integrin-dependent adhesive
      interactions. In addition, actin remodeling is important for facilitating the
      sustained signaling required for full T-cell activation. Although the
      relationship between T-cell signaling and cytoskeletal remodeling is complex, new
      molecular genetic tools are making it possible to investigate individual
      molecular interactions in the context of bona fide conjugate formation. We
      describe here the progress from our laboratory toward defining the pathways
      required for actin remodeling during conjugate formation. Our studies show that
      engagement of T-cell receptor (TCR) and leukocyte functional antigen-1 (LFA-1)
      leads to distinct effects on the remodeling of individual cytoskeletal elements.
      Downstream of TCR, we find that p56Lck (Lck) plays a critical role in integrin
      dependent adhesion independent of its ability to activate zeta-associated protein
      of 70 kDa (ZAP-70). TCR engagement also results in the assembly of a signaling
      complex that facilitates the activation of Wiskott-Aldrich syndrome protein
      (WASP) by colocalization with Cdc42-GTP. These events, together with other
      parallel actin regulatory pathways, induce localized actin polymerization at the
      site of APC binding.

PMID- 12234367
TI  - Alpha4 integrins and the immune response.
AB  - The alpha4 integrins (alpha4beta1 and alpha4beta7) play multiple roles in the
      immune system. Alpha4 integrins impact hematopoiesis, leukocyte trafficking in
      immune surveillance and inflammation, and leukocyte activation and survival. To
      perform these functions, alpha4 integrins act as both adhesive and signaling
      receptors. Paxillin, a signaling adapter molecule, binds directly to the alpha4
      subunit cytoplasmic domain, and its binding is regulated by serine
      phosphorylation of the alpha4 subunit. This regulated interaction of paxillin
      with the alpha4 subunit is likely to regulate the diverse functions of alpha4
      integrins in the immune system. Furthermore, this protein-protein interaction may
      provide novel targets for the modulation of the immune response.

PMID- 12234366
TI  - The immunological synapse: integrins take the stage.
AB  - Adhesive interactions play important roles in coordinating T-cell migration and
      activation, specifically in the formation of the immunological synapse (IS), a
      specialized cell-cell junction. Recent demonstrations show several molecules
      implicated in T-cell signaling, including Vav, ADAP, and Rap-1, have major roles
      in integrin regulation and place adhesion molecules at center stage in addressing
      the question: what are the signals involved in the formation of the IS and full T
      cell activation? This review focuses on the role of integrins as an essential
      system for both physical adhesion and signaling in T-cell activation. The role of
      integrins appears to be quite distinct from classical costimulation and has been
      largely overlooked due to the ubiquitous use of serum in lymphocyte functional
      assays. Each major signal transduction pathway has branches leading to the
      nucleus and others that feed back on cytoskeletal and membrane regulation at the
      IS.

PMID- 12234368
TI  - Integrin structure: new twists and turns in dynamic cell adhesion.
AB  - The divalent-cation-dependent binding of alphabeta heterodimeric integrins to
      their ligands regulates most cellular processes. Integrin-ligand interactions are
      tightly controlled by inside-out activation signals. Ligand-bound integrins in
      turn transduce outside-in signals typical of other receptors. Precise information
      of how ligands bind to integrins is restricted to that of a small vWF A-type
      domain present in some alpha-subunits (alphaA). Both inside-out and outside-in
      signals elicit tertiary and quaternary changes in integrins, but the precise
      nature and scope and of these changes are unknown. The recently solved structures
      of the extracellular segment of integrin alphaVbeta3 in its unliganded and
      liganded states are generating exciting new insights into the design, wiring,
      function and regulation of this protein family. The structures reveal a
      surprising degree of flexibility at defined regions in the structure that is
      potentially controlled by cations. The quaternary structure of the ligand-binding
      region bears a striking resemblance to the nucleotide-binding pocket of G
      proteins, implying analogous activation and signaling mechanisms. Structural
      links exist through which ligand-induced tertiary changes may be translated into
      quaternary changes and vice versa. The structures also raise the tantalizing
      hypothesis that alphaA is a regulated endogenous integrin ligand, so that no
      special regulatory features are needed in this integrin. These findings provide
      the framework for new investigations of structure-activity relationships in
      integrins, with important implications for targeting these receptors
      therapeutically [corrected].

PMID- 12234369
TI  - Integrin activation and structural rearrangement.
AB  - Among adhesion receptor families, integrins are particularly important in
      biological processes that require rapid modulation of adhesion and de-adhesion.
      Activation on a timescale of < 1 s of beta2 integrins on leukocytes and beta3
      integrins on platelets enables deposition of these cells at sites of inflammation
      or vessel wall injury. Recent crystal, nuclear magnetic resonance (NMR), and
      electron microscope (EM) structures of integrins and their domains lead to a
      unifying mechanism of activation for both integrins that contain and those that
      lack an inserted (I) domain. The I domain adopts two alternative conformations,
      termed open and closed. In striking similarity to signaling G-proteins,
      rearrangement of a Mg2+-binding site is linked to large conformational movements
      in distant backbone regions. Mutations that stabilize a particular conformation
      show that the open conformation has high affinity for ligand, whereas the closed
      conformation has low affinity. Movement of the C-terminal alpha-helix 10 A down
      the side of the domain in the open conformation is sufficient to increase
      affinity at the distal ligand-binding site 9,000-fold. This C-terminal "bell
      rope" provides a mechanism for linkage to conformational movements in other
      domains. Recent structures and functional studies reveal interactions between
      beta-propeller, I, and I-like domains in the integrin headpiece, and a critical
      role for integrin epidermal growth factor (EGF) domains in the stalk region. The
      headpiece of the integrin faces down towards the membrane in the inactive
      conformation, and extends upward in a "switchblade"-like opening upon activation.
      These long-range structural rearrangements of the entire integrin molecule
      involving interdomain contacts appear closely linked to conformational changes
      within the I and I-like domains, which result in increased affinity and
      competence for ligand binding.

PMID- 12234370
TI  - Mechanisms contributing to the activity of integrins on leukocytes.
AB  - Understanding how the integrins on leukocytes operate is important because these
      receptors control the activity of leukocytes in all phases of their lives. Thus
      integrins control leukocyte development and maturation in bone marrow, the
      circulation of naive cells in secondary lymphoid tissue, e.g. the lymph nodes,
      and leukocyte responses to inflammatory signals emanating from injured tissues.
      Using as an example LFA-1, which is expressed by all leukocytes, we outline how
      the activity of this integrin is modified to meet the challenges posed by these
      leukocyte activities. Briefly, we discuss three means by which LFA-1 is adapted
      to bind more efficiently to its chief ligand, ICAM-1. LFA-1 can undergo changes
      in conformation leading to increased affinity, can be clustered on the membrane
      and, finally, when activated can move into the lipid raft compartment of the
      membrane. The study of humans with the beta2 deficiency syndrome termed leukocyte
      adhesion deficiency (LAD)-1 and analysis of LFA-1 null mice has given further
      insight into integrin activation mechanisms and the in vivo roles of LFA-1 and
      other leukocyte integrins.

PMID- 12234371
TI  - Genetic analysis of integrin activation in T lymphocytes.
AB  - Among the myriad receptors expressed by T cells, the sine qua non is the CD3/T
      cell receptor (CD3/TCR) complex, because it is uniquely capable of translating
      the presence of a specific antigen into intracellular signals necessary to
      trigger an immune response against a pathogen or tumor. Much work over the past 2
      decades has attempted to define the signaling pathways leading from the CD3/TCR
      complex that culminate ultimately in the functions necessary for effective T cell
      immune responses, such as cytokine production. Here, we summarize recent advances
      in our understanding of the mechanisms by which the CD3/TCR complex controls
      integrin-mediated T cell adhesion, and discuss new information that suggests that
      there may be unexpected facets to this pathway that distinguish it from those
      previously defined.

PMID- 12234372
TI  - Integrin-dependent regulation of gene expression in leukocytes.
AB  - In addition to their role in strengthening intercellular adhesion, leukocyte
      integrins transduce signals which affect genetic programs, consequently defining
      cell phenotype and function. These signals can be independently sufficient, or
      can cooperate with other environmental stimuli to affect gene expression
      regulation. In the past several years, there has been an emergence of mechanistic
      data which contribute to our understanding of these critical integrin roles. In
      this review, we describe anchorage-dependent T lymphocyte proliferation and, in
      particular, how leukocyte integrin engagement overcomes the G1 to S cell cycle
      restriction point in antigen-activated T cells. The related role of alphaLbeta2
      integrin (LFA-1) as a T cell co-stimulatory molecule is discussed. This includes
      defining mechanisms whereby LFA-1 engagement enhances transcriptional activation
      of numerous genes by regulating its association with transcription modulators
      such as JAB-1, and through interaction with other gene-activating signaling
      complexes such as JAK-STATs. Evidence is presented to support that leukocyte
      integrin engagement provides potent signals which stabilize otherwise labile
      activation mRNA transcripts, including those encoding cytokine and extracellular
      matrix degrading proteins. These integrin-dependent mechanisms, all described
      recently, play important roles in T cell differentiation and proliferation,
      immune surveillance and inflammatory responses.

PMID- 12234373
TI  - Regulation of monocyte gene expression by the extracellular matrix and its
      functional implications.
AB  - By binding to extracellular matrix (ECM) proteins, integrins integrate signals
      from outside the cell and transmit them inwards, thereby providing cells with
      information about location and allowing them to respond to stimuli in a manner
      appropriate to their environment. This is particularly important for monocytes
      and macrophages, given their wide distribution throughout the body and the vital
      role they play in immune and inflammatory responses. Integrin-mediated
      interaction of monocytes with ECM is a potent regulator of gene expression and is
      strongly synergized by the presence of growth factors. This synergy between
      growth factors and integrins is also apparent in the overlap seen in their
      signaling pathways. Integrin-mediated interaction with ECM results in increased
      expression of numerous inflammatory and immune response genes, revealing an
      important role for ECM-integrin interaction in affecting monocyte function and
      thus impacting on the development of pathologies. This is of particular relevance
      in the context of immune and inflammatory responses, where integrin-mediated
      adhesive interactions with the ECM-rich peripheral tissues are central to the
      localization of both resident and infiltrating monocytes at inflammatory sites.
      Here, we will review the functional effects of integrin-ECM interactions on
      monocytes, with particular attention to the regulation of gene expression by ECM
      and its functional implications.

PMID- 12234374
TI  - Migration and differentiation of CD8+ T cells.
AB  - Antigen-specific responses by CD8+ T cells require direct cell-cell interactions
      between T cells and antigen-presenting cells (APC). Initially, naive T cells must
      communicate with APC in lymphoid organs. Once stimulated, the resulting effector
      cells interact with APC in peripheral tissues. To this end, T cells must migrate
      to discrete sites throughout the body where antigen may be found. Recent progress
      in the field has revealed that the migratory abilities of T cells are critically
      dependent on their differentiation state, which is shaped by a multitude of
      factors. Thus, naive T cells are normally restricted to recirculate between the
      blood and secondary lymphoid tissues, although in some autoimmune diseases they
      may also accumulate in chronically inflamed tissues. When CD8+ T cells encounter
      antigen and differentiate into short-lived effector CTL, they lose the ability to
      home to lymph nodes but gain access to peripheral tissues and sites of
      inflammation. Long-lived memory cells exist in (at least) two flavors: central
      memory cells that migrate to both lymphoid organs and peripheral sites of
      inflammation, and effector memory cells that are preferentially localized in non
      lymphoid tissues. Our current understanding of the interplay of T cell
      differentiation and migration has been boosted by the development of T-GFP mice,
      in which transgenic green fluorescent protein is expressed selectively in naive
      and central memory T cells, but not in effector cytotoxic T cells (CTL). This
      review will focus on recent studies in which T-GFP mice were used to dissect the
      traffic signals for naive T cell homing to secondary lymphoid organs, the factors
      that influence the differentiation of naive CD8+ T cells into cytotoxic and
      memory cells, as well as the in vivo trafficking routes of antigen-experienced
      subsets.

PMID- 12234375
TI  - Protein kinase ERK contributes to differential responsiveness of human myeloma
      cell lines to IFNalpha.
AB  - BACKGROUND: Despite IFNalpha has been used extensively in the treatment of
      multiple myeloma (MM), there are also several reports suggesting that IFNalpha
      may aggravate isease in some MM patients. That means the effect of IFNalpha on
      the growth of myeloma cells in vivo may be different. In this study, we selected
      two human myeloma cell lines that vary remarkably in response to IFNalpha and
      focused on elucidating the mechanism of differential IFNalpha responsiveness.
      RESULTS: Sko-007 is a myeloma cell line whose growth is arrested by IFNalpha;
      however, IFNalpha promoted the proliferation of the other myeloma cell line U266.
      We observed that the growth-stimulation effect of IFNalpha on U266 cells did not
      result from up-regulation of the IL-6 receptors on cell surface; while IFNalpha
      treatment on Sko-007 cells significantly reduced gp130 expression. Moreover, the
      transcription factors STAT3 and STAT1, which are involved in the JAK/STAT signal
      transduction pathway, can be activated in both IFNalpha-stimulated and -inhibited
      myeloma cell lines; while the activation of the protein kinase ERK, which is
      involved in the Ras/MAPK signal transduction pathway, can be down-regulated in
      IFNalpha-arrested Sko-007 cells and up-regulated in IFNalpha-stimulated U266
      cells. In addition, both IFNalpha-induced growth-stimulation effect and the up
      regulated activation of ERK in U266 cells were efficiently inhibited by PD98059,
      the specific inhibitor of MAPK/ERK kinase (MEK). CONCLUSION: Myeloma cells
      responsiveness to IFNalpha is heterogeneous and the activation state of ERK in
      the Ras/MAPK signalling pathway mainly contributed to this difference.

PMID- 12234376
TI  - BRCA1 Zinc RING Finger Domain Disruption Alters Caspase Response in Ovarian
      Surface Epithelial Cells.
AB  - BACKGROUND: The frequently occurring 185delAG mutation occurs in the amino
      terminal zinc RING domain of the breast and ovarian cancer susceptibility gene,
      BRCA1. We sought to determine differential cell viability and apoptotic response
      of human ovarian surface epithelial cells with and without the 185delAG mutation.
      RESULTS: BRCA1wt and BRCA1+ cells were treated with staurosporine. Cell
      proliferation assays showed BRCA1wt cells grew to a greater extent compared to
      BRCA1+ cells. Trypan blue exclusion assays confirmed this observation. Western
      immunoblot analysis revealed that caspase 3 levels were higher after
      staurosporine treatment in BRCA1+ cells than in wild type cells, while full
      length DNA Fragmentation Factor 45 levels were lower in BRCA1+ cells. While there
      was no significant difference in levels of excision repair cross complementing
      protein1 (ERCC1) with BRCA1 status, BRCA1+ cells demonstrated cleavage of
      polyribose ADP polymerase (PARP) before wild type cells. CONCLUSIONS: Disruption
      of the BRCA1 RING domain caused altered cell viability and caspase-dependent
      apoptotic response after chemotoxic stress.

PMID- 12234377
TI  - Different glycosylation of cadherins from human bladder non-malignant and cancer
      cell lines.
AB  - BACKGROUND: The aim of the present study was to determine whether stage of
      invasiveness of bladder cancer cell lines contributes to alterations in glycan
      pattern of their cadherins. RESULTS: Human non-malignant epithelial cell of
      ureter HCV29, v-raf transfected HCV29 line (BC3726) and transitional cell cancers
      of urine bladder Hu456 and T24 were grown in cell culture. Equal amounts of
      protein from each cell extracts were separated by SDS-PAGE electrophoresis and
      were blotted on an Immobilon P membrane. Cadherins were immunodetected using anti
      pan cadherin mAb and lectin blotting assays were performed, in parallel. N
      oligosaccharides were analysed by specific reaction with Galanthus nivalis
      agglutinin (GNA), Sambucus nigra agglutinin (SNA), Maackia amurensis agglutinin
      (MAA), Datura stramonium agglutinin (DSA), Aleuria aurantia agglutinin (AAA),
      Phaseolus vulgaris agglutinin (PHA-L) and wheat germ agglutinin (WGA). The
      cadherin from HCV29 cell line possessed bi- and/or 2,4-branched triantennary
      complex type glycans, some of which were alpha2,6-sialylated. The cadherin from
      BC3726 cell line exhibited exclusively high mannose type glycans. Cadherins from
      Hu456 and T24 cell lines expressed high mannose type glycans as well as beta1,6
      branched oligosaccharides with poly-N-acetyllactosamine structures and alpha2,3
      linked sialic acid residues. Additionally, the presence of fucose and alpha2,6
      sialic acid residues on the cadherin from T24 cell line was detected.
      CONCLUSIONS: These results indicate that N-glycosylation pattern of cadherin from
      bladder cancer cell line undergoes modification during carcinogenesis.

PMID- 12234378
TI  - Primary Research: Short Communication: Evidence Supporting Rare AIDS-Kaposi's
      Sarcoma Metastasis In Keeping With Their Vascular Endothelial Evolution.
AB  - BACKGROUND: It is postulated that the unusual manifestations of Kaposis's sarcoma
      cells in nonendothelial brain tissues and on eyeballs in advanced acquired immune
      deficiency syndrome (AIDS) cases are metastasized AIDS-Kaposi's sarcoma cells
      arising from vascular endothelial cells. METHODS: Experiments were performed to
      explore the above hypothesis by testing for intercellular adhesion molecule-1
      (CD54 antigens) on cutaneous AIDS-Kaposi's sarcoma cells as well as on AIDS
      Kaposi's sarcoma cells isolated from eyeballs as studies have illustrated that,
      unlike localized Kaposi's sarcoma cells of primary lesions, proliferating
      Kaposi's sarcoma cells in proximity to primary lesions express a negative or
      diminished phenotype when evaluated for identical surface antigens. Parallel CD54
      antigen tests were done on vascular endothelial cells and monocytes/macrophages
      as endothelial cells are considered evolutionarily related to Kaposi's sarcoma
      cells and monocytes/macrophages are ideal CD54 antigen positive controls.
      RESULTS: Our data showed that only AIDS-Kaposi's sarcoma cells of the eyes did
      not express CD54 antigens. CONCLUSIONS: We therefore report that our findings
      support the postulation suggesting AIDS-Kaposi's sarcoma dissemination in
      advanced AIDS patients in keeping with their vascular endothelial heredity.

PMID- 12234379
TI  - Long-term reductions in tinnitus severity.
AB  - BACKGROUND: This study was undertaken to assess long-term changes in tinnitus
      severity exhibited by patients who completed a comprehensive tinnitus management
      program; to identify factors that contributed to changes in tinnitus severity
      within this population; to contribute to the development and refinement of
      effective assessment and management procedures for tinnitus. METHODS: Detailed
      questionnaires were mailed to 300 consecutive patients prior to their initial
      appointment at the Oregon Health & Science University Tinnitus Clinic. All
      patients were then evaluated and treated within a comprehensive tinnitus
      management program. Follow-up questionnaires were mailed to the same 300 patients
      6 to 36 months after their initial tinnitus clinic appointment. RESULTS: One
      hundred ninety patients (133 males, 57 females; mean age 57 years) returned
      follow-up questionnaires 6 to 36 months (mean = 22 months) after their initial
      tinnitus clinic appointment. This group of patients exhibited significant long
      term reductions in self-rated tinnitus loudness, Tinnitus Severity Index scores,
      tinnitus-related anxiety and prevalence of current depression. Patients who
      improved their sleep patterns or Beck Depression Inventory scores exhibited
      greater reductions of tinnitus severity scores than patients who continued to
      experience insomnia and depression at follow-up. CONCLUSIONS: Individualized
      tinnitus management programs that were designed for each patient contributed to
      overall reductions in tinnitus severity exhibited on follow-up questionnaires.
      Identification and treatment of patients experiencing anxiety, insomnia or
      depression are vital components of an effective tinnitus management program.
      Utilization of acoustic therapy also contributed to improvements exhibited by
      these patients.

PMID- 12234380
TI  - Peroxynitrite decomposition catalyst prevents apoptotic cell death in a human
      astrocytoma cell line incubated with supernatants of HIV-infected macrophages.
AB  - BACKGROUND: Oxidative stress has shown to contribute in the mechanisms underlying
      apoptotic cell death occurring in AIDS-dementia complex. Here we investigated the
      role of peroxynitrite in apoptosis occurring in astroglial cells incubated with
      supernatants of HIV-infected human primary macrophages (M/M). RESULTS: Flow
      cytometric analysis (FACS) of human cultured astrocytes shortly incubated with
      HIV-1-infected M/M supernatants showed apoptotic cell death, an effect
      accompanied by pronounced staining for nitrotyrosine (footprint of peroxynitrite)
      and by abnormal formation of malondialdehyde (MDA). Pretreatment of astrocytes
      with the peroxynitrite decomposition catalyst FeTMPS antagonized HIV-related
      astrocytic apoptosis, MDA formation and nitrotyrosine staining. CONCLUSIONS:
      Taken together, our results suggest that inhibition of peroxynitrite leads to
      protection against peroxidative stress accompanying HIV-related apoptosis of
      astrocytes. Overall results support the role of peroxynitrite in HIV-related
      programmed death of astrocytes and suggest the use of peroxynitrite decomposition
      catalyst to counteract HIV-1-related neurological disorders.

PMID- 12234383
TI  - Combating Kinetoplastid diseases.

PMID- 12234381
TI  - Reactivation of a silenced H19 gene in human rhabdomyosarcoma by demethylation of
      DNA but not by histone hyperacetylation.
AB  - BACKGROUND: The active copy of the imprinted gene H19 is turned off by
      inappropriate methylation in several pediatric tumors including Wilms' Tumour and
      embryonal rhabdomyosarcoma. H19 controls in cis the linked Insulin-like Growth
      Factor 2 (IGF2) gene, encoding an important growth factor. Recent work has
      suggested that methylation of a gene may lead to deacetylation of its associated
      histones and that silenced genes can be reactivated by increasing histone
      acetylation levels. RESULTS: Treatment of a rhabdomyosarcoma cell line which has
      a silent, methylated H19 gene with histone deacetylase (HDAC) inhibitors under
      conditions which gave maximal hyperacetylation of histone 4, both globally and at
      the H19 gene itself could not reactivate H19 or affect the active Insulin-like
      Growth Factor 2 (IGF2) gene, but caused clear up-regulation of the Tissue-type
      Plasminogen Activator (TPA) gene, a non-imprinted gene known to respond to
      changes in histone acetylation. In contrast, mild treatment of the cells with the
      methylation inhibitor 5-AzaC-2'-deoxycytidine (AzaC) on its own was able to
      reactivate H19. Combining AzaC treatment with HDAC inhibitors gave a reduced
      rather than enhanced reactivation. These findings were confirmed in mouse primary
      liver and kidney explants which maintain normal imprinting, where we also found
      that the silent Igf2 gene could not be reactivated by HDAC inhibitors.
      CONCLUSION: These results suggest that DNA methylation rather than histone
      acetylation is the primary determinant of silencing of H19 in rhabdomyosarcoma.

PMID- 12234384
TI  - Salivaria or Stercoraria? The Trypanosoma rangeli dilemma.
AB  - The taxonomic status of Trypanosoma rangeli as well as the tools for its
      molecular characterization is briefly commented.

PMID- 12234385
TI  - What can we hope to gain for trypanosomiasis control from molecular studies on
      tsetse biology ?
AB  - At times of crisis when epidemics rage and begin to take their toll on affected
      populations, as we have been witnessing with African trypanosomiasis in
      subSahara, the dichotomy of basic versus applied research deepens. While
      undoubtedly the treatment of thousands of infected people is the top priority,
      without continued research and development on the biology of disease agents and
      on ecological and evolutionary forces impacting these epidemics, little progress
      can be gained in the long run for the eventual control of these diseases. Here,
      we argue the need for additional research in one under-investigated area, that is
      the biology of the tsetse vector. Lacking are studies aimed to understand the
      genetic and cellular basis of tsetse interactions with trypanosomes as well as
      the genetic and biochemical basis of its ability to transmit these parasites. We
      discuss how this knowledge has the potential to contribute to the development of
      new vector control strategies as well as to improve the efficacy and
      affordability of the existing control approaches.

PMID- 12234387
TI  - PCR identification of Trypanosoma lewisi, a common parasite of laboratory rats.
AB  - Trypanosoma (Herpetosoma) lewisi is a trypanosome of the sub-genus Herpetosoma
      (Stercoraria section), parasite of rats (Rattus rattus and Rattus norvegicus)
      transmitted by fleas. T. lewisi has a stringent species specificity and cannot
      grow in other rodents such as mice. Rats are infected principally by oral route,
      through contamination by flea faeces or ingestion of fleas. Trypanosoma lewisi
      infections in rat colonies can interfere with research protocols and fleas of
      wild rats are often the source of such infections. Currently, diagnosis of T.
      lewisi in rats is performed by microscopic observation of stained blood smears.
      In the course of a research project at CIRDES, a T. lewisi infection was detected
      in the rat colony. In this study we evaluated PCR primer sets for their ability
      to diagnose multiple species of trypanosomes with a single amplification. We show
      that the use of ITS1 sequence of ribosomal DNA provides an efficient and
      sensitive assay for detection and identification of T. lewisi infection in rats
      and recommend the use of this assay for monitoring of T. lewisi infections in rat
      colonies.

PMID- 12234386
TI  - From the cell biology to the development of new chemotherapeutic approaches
      against trypanosomatids: dreams and reality.
AB  - Members of the Trypanosomatidae family comprise a large number of species that
      are causative agents of important diseases such as sleeping sickness, Chagas'
      disease and Leishmaniasis. These organisms are also of biological interest since
      they are able to change the morphology according to the environment where they
      live, through a process of reversible cell transformation, and possess structures
      and organelles that are not found in mammalian cells. This review analyses the
      process of transformation, which takes place during the life cycle of Trypanosoma
      cruzi in the vertebrate and invertebrate hosts. Special attention is given to the
      interaction of the parasite with vertebrate cells. In addition, the present
      knowledge of structures and organelles such as the nucleus, the plasma membrane,
      the sub-pellicular microtubules, the flagellum, the kinetoplast-mitochondrion
      complex, the peroxisome (glycosome), the acidocalcisome and the structures and
      organelles involved in the endocytic pathway, is reviewed from a cell biology
      perspective. The possible use of available data for the development of new anti
      parasite drugs is also discussed.

PMID- 12234388
TI  - Molecular determinants and regulation of Leishmania virulence.
AB  - A Leishmania model to explain microbial virulence in chronic infectious diseases
      is proposed. All these diseases progress from infection to symptomatic phase to
      host death or recovery. The outcome of each phase is depicted to result from the
      interactions of a distinct group of parasite molecules with a specific host
      immune compartment. The first group consists of invasive/evasive determinants,
      which are largely parasite cell surface and secreted molecules. Their activities
      help parasites establish infection by overcoming host immunologic and non
      immunologic barriers. These determinants do not cause disease per se, but are
      indispensable for infection necessary for the development of a disease-state. The
      second group of parasite molecules consists of "pathoantigenic" determinants -
      unique parasite epitopes present often within otherwise highly conserved
      cytoplasmic molecules. Immune response against these determinants is thought to
      result in immunopathology manifested as clinical signs or symptoms, namely the
      virulent phenotype. The third group of parasite molecules is hypothetically
      perceived as vaccine determinants. Their interactions with the host immune system
      lead to the elimination or reduction of parasites to effect a clinical cure.
      Differential expression of these determinants alone by parasites may alter their
      interactions with the hosts. Virulent phenotype is consequently presented as a
      spectrum of manifestations from asymptomatic infection to fatality. A secondary
      level of regulation lies in host genetic and environmental factors. The model
      suggests that different parasite determinants may be targeted by different
      strategies to achieve more effective control of leishmaniasis and other similar
      diseases.

PMID- 12234389
TI  - A Problem with the Individual Approach in the WHO Health Inequality Measurement.
AB  - BACKGROUND: In the World Health Report 2000, the World Health Organization made
      the controversial choice to measure inequality across individuals rather than
      across groups, the standard in the field. This choice has been widely discussed
      and criticized. DISCUSSION: We look at the three questions: (1) is the World
      Health Organization's health inequality measure value-free as it claims? (2) if
      it is not, what is the normative position implied by its approach when measuring
      health inequality? and (3) is the individual approach a logically consistent
      methodological choice for that normative position? SUMMARY: We argue that the
      World Health Organization's health inequality measure is not value-free. If it
      was, the health inequality information that the measurement collected could not
      reasonably be included in its ranking of how well national health systems
      performed. The World Health Organization's normative position can be interpreted
      as a quite expansive view of justice, in which health distributions that have
      causes amenable to human intervention are considered to be matters of justice.
      Our conclusion is that if the World Health Organization's health inequality
      measure is to be interpreted meaningfully in a policy context, its conceptual
      underpinning must be re-evaluated.

PMID- 12234391
TI  - Development of Japanese neurosurgery: from the Edo era to 1973.
AB  - IN JAPAN, ALTHOUGH eminent surgeons have performed major operations while the
      patient is under general anesthesia since the end of the 18th century and the
      beginning of the 19th century, neurosurgical operations were performed only
      sporadically for many years after 1877. The Japanese Neurological Society was
      formed in 1948. Independent departments of neurosurgery have been established
      since 1962. The Board of Neurological Surgery was founded in 1966. The Fifth
      International Congress of Neurological Surgery, held in Tokyo in 1973, strongly
      influenced young Japanese neurosurgeons.

PMID- 12234390
TI  - Annotated Bibliography on Equity in Health, 1980-2001.
AB  - The purposes of this bibliography are to present an overview of the published
      literature on equity in health and to summarize key articles relevant to the
      mission of the International Society for Equity in Health (ISEqH). The intent is
      to show the directions being taken in health equity research including theories,
      methods, and interventions to understand the genesis of inequities and their
      remediation. Therefore, the bibliography includes articles from the health equity
      literature that focus on mechanisms by which inequities in health arise and
      approaches to reducing them where and when they exist.

PMID- 12234392
TI  - The current state of neurosurgery in Japan.
AB  - JAPAN HAS TWO large neurosurgical societies, the Japan Neurosurgical Society
      (JNS) and the Japanese Congress of Neurological Surgeons (Japanese CNS). The JNS
      was founded in 1948, and the Japanese CNS in 1981. The total number of
      neurosurgeons in Japan exceeds 7500, with 5432 board certified. There are 1340
      training centers for neurosurgery in Japan; they are classified into two
      categories: Category A centers and Category C centers (training subcenters). For
      a neurosurgeon to be eligible to take the specialty board examination, he or she
      is required to have finished at least 6 years of training at a designated
      training center. A characteristic of Japanese neurosurgery is that neurosurgeons
      are engaged not only in surgical operations but also in various related
      activities, including performing radiological diagnostic procedures, such as
      angiography and endovascular surgery; working in the emergency room; and
      sometimes participating in neurorehabilitation and gamma knife treatment. In
      addition, a large number of neurosurgeons are engaged in research in various
      related fields. The JNS began to publish its official journal in 1948, initially
      in the Japanese language. Since 1990, the journal has been published exclusively
      in English (Neurologia Medico-chirurgica), whereas the official journal of the
      Japanese CNS is published in Japanese (Japanese Journal of Neurosurgery). Japan
      is blessed with advanced diagnostic and surgical technologies and instruments.
      They are available as needed throughout the country. Medical insurance is fully
      covered by the government or public insurance system; there is basically no
      private insurance in Japan. This article mentions socioeconomic problems relating
      to neurosurgical practice.

PMID- 12234393
TI  - The Kabuto, or the Japanese helmet: evolution from war implement to status
      symbol.
AB  - WARRIORS THROUGHOUT THE AGES have considered the unprotected head to be
      particularly vulnerable. The traditional Japanese helmet, the Kabuto, was the
      part of a protective suit of armor that reflected the wearer's character and
      personality. Over time, it changed from a primarily protective device to a
      vehicle for the expression of a distinctly Japanese sense of magnificent
      artistry. Each Kabuto was custom-made, and these helmets remain without peer in
      the world. They were designed and crafted to answer the demands of their era, and
      thus they provide historical evidence not only of the state of Japanese warfare,
      but also of social organization, metallurgical knowledge, artisanship, and
      aesthetic sensibility. Even now, during the national Golden Week Festival in
      early May, Kabuto are displayed in the alcoves of Japanese homes as a petition
      that the boys in the house be granted courage and good health. Thus, even in
      modern Japan, the Kabuto represents a talisman. We present an overview of the
      evolution of the Kabuto, with special reference to the Japanese sword and the
      warrior tradition.

PMID- 12234394
TI  - The role of radiosurgery for the treatment of pineal parenchymal tumors.
AB  - OBJECTIVE: Radiosurgery is an appealing alternative management strategy for
      selected patients with biopsy-proved pineal parenchymal tumors. The purpose of
      this report was to clarify its role in conjunction with other surgical,
      radiation, and medical approaches. METHODS: We retrospectively evaluated 16
      patients who had undergone radiosurgery as the primary or adjuvant treatment for
      pineal parenchymal tumors. Ten patients (62.5%) had pineocytomas, two (12.5%) had
      mixed pineocytoma and pineoblastoma, and four (25%) had pineoblastomas. The mean
      marginal dose was 15 Gy, and the mean tumor volume was 5.0 cm(3). The mean follow
      up periods from the time of diagnosis or the time of radiosurgery were 61 and 52
      months, respectively. RESULTS: The overall actuarial 2- and 5-year survival rates
      after diagnosis were 75.0 and 66.7%, respectively. In 14 patients who were
      evaluated with imaging, 4 (29%) demonstrated complete remission, 8 (57%) had
      partial remission, 2 (14%) had no change, and no patient had local progression.
      The local tumor control rate (complete remission, partial remission, or no
      change) was 100%. Five patients died during follow-up. One patient with a
      pineocytoma and three patients with pineoblastomas died secondary to
      leptomeningeal or extracranial spread tumor. No cause of death was established
      for one patient. Two patients developed adverse radiation effects after
      radiosurgery. CONCLUSION: Our initial experience suggests that stereotactic
      radiosurgery is a valuable primary management modality for patients with
      pineocytomas. As adjuvant therapy, radiosurgery may be used to boost local tumor
      dose during multimodality management of malignant pineal parenchymal tumors.

PMID- 12234395
TI  - Fractionated stereotactic radiotherapy for the treatment of optic nerve sheath
      meningiomas: preliminary observations of 33 optic nerves in 30 patients with
      historical comparison to observation with or without prior surgery.
AB  - OBJECTIVE: We investigated the safety and efficacy of stereotactic radiotherapy
      as an alternative therapy to surgical resection for optic nerve sheath
      meningiomas (ONSMs). METHODS: Thirty patients and 33 optic nerves with ONSMs were
      treated with conventional fractionated stereotactic radiotherapy treatment (CF
      SRT) between July 1996 and May 2001 with the use of a 6-MeV LINAC designed for
      and dedicated to radiosurgery. The LINAC technique involved daily CF-SRT
      involving a relocatable frame, an average of three isocenters, and high-radiation
      dose conformality established by noncoplanar arc beam shaping and differential
      beam weighting. The patients who were treated with CF-SRT were followed
      clinically with serial visual fields and radiographically with both magnetic
      resonance imaging and functional (111)In-octreotide single-photon emission
      computed tomography. The results of treatment were compared with a historical
      control group of ONSM patients who were either observed or treated surgically and
      then observed. RESULTS: Our study population comprised 18 women and 12 men with a
      median age of 44 years (age range, 20-76 yr). The median isosurface radiation
      dose was 51 Gy (dose range, 50-54.0 Gy), and the median clinical follow-up time
      was 89 weeks (range, 9-284 wk). Of 22 optic nerves with vision before CF-SRT, 20
      nerves (92%) demonstrated preserved vision, and 42% manifested improvement in
      visual acuity and/or visual field at follow-up. Comparison of our patients with a
      historical control group revealed preserved vision in only 16% of patients in a
      comparable period of observation, along with a 150% greater probability of visual
      improvement. Four patients (13%) had posttreatment morbidities, including visual
      loss (two patients), optic neuritis (one patient), and transient orbital pain
      (one patient). On magnetic resonance imaging studies, there was no evidence of
      tumor progression or recurrence in all patients, including tumor volume
      reductions noted in four patients. All six patients monitored with (111)In
      octreotide scintigraphy demonstrated significant decreases in tumor activity
      after CF-SRT. CONCLUSION: To date, this article describes the largest reported
      series of ONSMs. Although longer follow-up is necessary, we think that CF-SRT
      represents a safe alternative to surgery and offers a higher likelihood of
      preserved or improved vision in patients with ONSM. Our analysis suggests that CF
      SRT is also preferable to observation. Functional (111)In-octreotide single
      photon emission computed tomographic scintigraphy provides a useful technique for
      the assessment of tumor control that complements serial posttreatment magnetic
      resonance imaging in patients with ONSMs.

PMID- 12234396
TI  - Radiosurgery for treatment of recurrent intracranial hemangiopericytomas.
AB  - OBJECTIVE: Hemangiopericytomas are highly aggressive meningeal tumors with
      tendencies for recurrence and metastasis. The purpose of this retrospective,
      single-institution review was to evaluate the efficacy and role of stereotactic
      radiosurgery in the management of recurrent hemangiopericytomas. METHODS: We
      reviewed data for patients who underwent stereotactic radiosurgery at the
      University of Pittsburgh between 1987 and 2001. Fourteen patients underwent
      radiosurgery for 15 discrete tumors. Prior treatments included transsphenoidal
      resection (n = 1), craniotomy and resection (n = 27), embolization (n = 1), and
      conventional radiotherapy (n = 7). Clinical and radiological responses were
      evaluated. Follow-up periods varied from 5 to 76 months (mean, 31.3 mo; median,
      21 mo). The mean radiation dose to the tumor margin was 15 Gy. RESULTS: Seventy
      nine percent of patients (11 of 14 patients) with recurrent hemangiopericytomas
      demonstrated local tumor control after radiosurgery. Twelve of 15 tumors (i.e.,
      80%) dramatically decreased in size on follow-up imaging scans. Regional
      intracranial recurrences were retreated with radiosurgery for two patients (i.e.,
      15%); neither of those two patients experienced long-term tumor control. Local
      recurrences occurred 12 to 75 months (median, 21 mo) after radiosurgery. Local
      tumor control and survival rates at 5 years after radiosurgery were 76 and 100%,
      respectively (Kaplan-Meier method). We could not correlate prior irradiation or
      tumor size with tumor control. Twenty-nine percent of the patients (4 of 14
      patients) developed remote metastases. Radiosurgery did not seem to offer
      protection against the development of intra- or extracranial metastases.
      CONCLUSION: Gamma knife radiosurgery provided local tumor control for 80% of
      recurrent hemangiopericytomas. When residual tumor is identified after resection
      or radiotherapy, early radiosurgery should be considered as a feasible treatment
      modality. Despite local tumor control, patients are still at risk for distant
      metastasis. Diligent clinical and radiological follow-up monitoring is necessary.

PMID- 12234397
TI  - Correlations between magnetic resonance spectroscopy and image-guided
      histopathology, with special attention to radiation necrosis.
AB  - OBJECTIVE: The differentiation of tumor recurrence from radiation necrosis in
      patients with malignant gliomas who have been treated previously remains a
      challenge. Magnetic resonance imaging, single-photon emission computed
      tomography, and positron emission tomography cannot provide definitive
      histopathological insight. Multivoxel proton magnetic resonance spectroscopic
      imaging ((1)H MRSI) may be reliable in guiding the clinical management of
      untreated patients; however, its value in managing previously treated patients
      remains unclear. METHODS: Twenty-seven patients who had been treated previously
      with surgery, radiotherapy, and chemotherapy and reoperated for clinical and/or
      radiographic signs that caused suspicion for recurrent disease were studied.
      Tissues were categorized into four groups: spectroscopically normal, pure tumor,
      mixed tumor and radiation necrosis, and pure radiation necrosis. Spectral data
      for choline (Cho), lipid-lactate (Lip-Lac), N-acetylaspartate, and creatine (Cr)
      were analyzed as Cho/normal Cr (nCr), Lip-Lac/Cho, Lip-Lac/nCr, N
      acetylaspartate/Cho, N-acetylaspartate/nCr, and Cho/normal Cho (nCho).
      Stereotactic biopsies were obtained within 48 hours of (1)H MRSI and were
      directly correlated digitally with (1)H MRSI data. Logistic regression analysis
      was performed on the basis of data obtained from 99 (1)H MRSI observations to
      determine whether the (1)H MRSI ratios varied according to tissue category.
      RESULTS: (1)H MRSI ratios were found to distinguish pure tumor from pure
      necrosis. The odds of a biopsy's being pure tumor and having either a Cho/nCr
      value greater than 1.79 or a Lip-Lac/Cho value less than 0.75 are seven times the
      odds of that biopsy's being pure necrosis (odds ratio, 7.00; P = 0.0136). The
      odds of a biopsy's being pure necrosis and having either a Cho/nCr value less
      than 0.89 or a Cho/nCho value less than 0.66 are six times the odds of that
      biopsy's being pure tumor (odds ratio, 5.71; P = 0.0329). The odds of a biopsy's
      being pure necrosis and having either a Lip-Lac/Cho value greater than 1.36 or a
      Lip-Lac/nCr value greater than 2.84 are more than five times the odds of the
      biopsy's being pure tumor (odds ratio, 5.25; P = 0.0322). In addition, although
      only marginally significant, Lip-Lac/Cho and Lip-Lac/nCr ratios distinguish pure
      tumor from pure necrosis. No values suggested that mixed specimens could be
      distinguished in a statistically significant way from either pure tumor or pure
      necrosis. CONCLUSION: The data that we gathered suggest that metabolite ratios
      derived on the basis of (1)H MRSI spectral patterns do allow reliable
      differential diagnostic statements to be made when the tissues are composed of
      either pure tumor or pure necrosis, but the spectral patterns are less definitive
      when tissues composed of varying degrees of mixed tumor and necrosis are
      examined.

PMID- 12234398
TI  - Role of venous drainage in cerebral arteriovenous malformation surgery, as
      related to the development of postoperative hyperperfusion injury.
AB  - OBJECTIVE: To elucidate the role of venous drainage in cerebral arteriovenous
      malformation (AVM) surgery, with respect to the development of postoperative
      hyperperfusion injury. METHODS: For 52 patients with supratentorial AVMs,
      cortical capillary oxygenation (SaO(2)) was assessed intraoperatively, before and
      after resection, in the vicinity of the AVMs, by using a microspectrophotometric
      method. Assessed areas were defined as being related to feeding arteries or
      draining veins or as distant areas. Patients were divided into three groups on
      the basis of postoperative angiographic findings, as follows: Group 1, all former
      draining veins preserved (8 patients); Group 2, > or =1 former draining vein
      visible (12 patients); Group 3, no former draining veins visible (32 patients).
      Patients and SaO(2) values were pooled and compared by using paired and unpaired
      t tests (P < 0.05). Venous circulation times were calculated from digital
      subtraction angiography films. RESULTS: The postresectional relative increases in
      SaO(2) values were highest in draining vein areas (+40.8%, compared with +25% in
      feeder areas and +25.5% in distant areas). Five postoperative hyperemic
      complications occurred (9.6%), none in Group 1 (with all draining veins
      preserved), two (16.7%) in Group 2, and three (9.4%) in Group 3 (with all
      draining veins occluded). The lowest preresectional SaO(2) values (31.7 +/- 6.2%)
      were measured in the drainer areas of the five patients who subsequently
      developed hyperperfusion injuries. Among those patients, postresectional
      increases in SaO(2) values were significantly greater in drainer areas (+167.8%)
      than in feeder areas (+28.3%) or distant areas (+25.8%). Postoperative venous
      circulation times in former draining veins in Group 2 were significantly greater
      than those in Group 1 (8.9 +/- 1.5 s versus 6.3 +/- 0.6 s). Circulation times in
      normal veins in the five patients with hyperperfusion injury increased from 5.6
      +/- 1.0 seconds (preoperatively) to 8.4 +/- 1.9 seconds (postoperatively).
      CONCLUSION: Postoperative hyperperfusion injury after resection of cerebral AVMs
      can be explained on the basis of unconstrained arterial inflow into cortical
      areas, which are rendered hypoxic/ischemic by longstanding preoperative venous
      hypertension. The risk for postoperative breakthrough complications seems higher
      in the presence of multiple draining veins, which also participate in the
      physiological venous drainage system of the ipsilateral hemisphere.

PMID- 12234399
TI  - Management of intracranial vertebral artery dissections initially presenting
      without subarachnoid hemorrhage.
AB  - OBJECTIVE: The clinical and angiographic follow-up results for intracranial
      vertebral artery (VA) dissections that initially presented without subarachnoid
      hemorrhage (SAH) were retrospectively investigated, to clarify their management.
      METHODS: Twenty-one patients with VA dissections that initially presented without
      SAH were studied. Initial angiography revealed aneurysmal dilation in 11 cases
      (typical pearl-and-string sign in 8 cases, aneurysmal dilation only in 2, and
      aneurysmal dilation with double-lumen sign in 1), occlusion in 7, double-lumen
      sign in 2, and string-like stenosis in 1. Nine patients (six with pearl-and
      string sign, one with occlusion with aneurysmal dilations, and two with double
      lumen sign), including three patients who experienced subsequent SAH, underwent
      endovascular proximal parent artery occlusion. The other 12 patients were treated
      conservatively. All patients were monitored with magnetic resonance angiography
      or digital subtraction angiography. RESULTS: Three patients experienced
      subsequent SAH, 1 day (two patients) or 51 months after onset. Follow-up
      angiographic assessments of the 20 patients demonstrated complete resolution in
      five cases, reduction of aneurysmal dilation in one case, and partial
      recanalization in one case. However, enlargement or formation of an aneurysmal
      dilation was recognized in four cases and progression of dissection was observed
      in one case. Eighteen patients experienced good recoveries, and three patients
      demonstrated moderate disabilities as a result of the initial ischemic insult.
      CONCLUSION: The risk of bleeding from unruptured VA dissections is higher than
      previously considered. Therefore, endovascular treatment should be considered for
      patients with VA dissections with relatively large or growing aneurysmal
      dilations.

PMID- 12234400
TI  - Evaluation of vasospasm after subarachnoid hemorrhage by use of multislice
      computed tomographic angiography.
AB  - OBJECTIVE: Multislice computed tomographic angiography (CTA) can provide clearer
      vascular images, even of the peripheral arteries, than conventional CTA.
      Multislice CTA was compared with digital subtraction angiography (DSA) for the
      detection of cerebral vasospasm in patients with acute aneurysmal subarachnoid
      hemorrhage (SAH) to analyze whether multislice CTA can replace DSA in the
      detection of vasospasm after SAH. METHODS: Within 72 hours after the onset of
      symptoms, multislice CTA and DSA were performed in 20 patients with SAH.
      Multislice CTA and DSA were repeated on Day 7 to assess cerebral vasospasm.
      Regions of interest were established in the proximal and distal segments of the
      anterior and middle cerebral arteries on both multislice CTA and DSA images, and
      the agreement between the severity of vasospasm on multislice CTA and DSA images
      was statistically compared. The multislice Aquilon computed tomography system
      (Toshiba, Inc., Tokyo, Japan) used the following parameters: 1 mm collimation and
      3.5 mm per rotation table increment (pitch, 3.5). RESULTS: The degree of
      vasospasm as revealed by multislice CTA correlated significantly with the degree
      of vasospasm revealed by DSA (P < 0.0001). The agreement between the severity of
      vasospasm on multislice images obtained via CTA and DSA in the overall, proximal,
      and distal segments of the cerebral arteries was 91.6, 90.8, and 92.3%,
      respectively. CONCLUSION: Multislice CTA can detect angiographic vasospasm after
      SAH with accuracy equal to that of DSA.

PMID- 12234401
TI  - Cholinergic dysfunction in cognitive impairments after aneurysmal subarachnoid
      hemorrhage.
AB  - OBJECTIVE: Although cognitive impairments have been observed after subarachnoid
      hemorrhage (SAH), little is known about their neurobiological bases. To examine
      cholinergic function in such patients, we used a known test for Alzheimer's
      disease based on an exaggerated pupil dilation response to a cholinergic
      antagonist, tropicamide (the tropicamide drop test). METHODS: Seventeen patients
      who were treated surgically after aneurysmal SAH were divided into two groups on
      the basis of their scores on the Mini-Mental State Examination (MMSE): Group A
      (MMSE > or =28) and Group B (MMSE < or =27). The mean interval of time between
      surgery and administration of the MMSE was 4.7 +/- 2.1 years for Group A and 4.2
      +/- 1.3 years for Group B. The tropicamide drop test was performed within 1 month
      after the MMSE for each patient. After measurement of the baseline pupil diameter
      (R1, right pupil size: L1, left pupil size), one drop of 0.01% tropicamide was
      applied to the right eye and physiological saline to the left eye. Pupil diameter
      (R2, right pupil size; L2, left pupil size) was then remeasured. Data were
      represented as the dilation ratio of the right pupil (R2/R1) and as the relative
      dilation ratio of the right pupil to that of the left pupil (R2L1/R1L2). RESULTS:
      The mean dilation ratio of the right pupil (R2/R1) was higher in Group B (1.13 +/
      0.09) than in Group A (1.07 +/- 0.11), although the difference did not reach
      statistical significance (P = 0.18). The relative dilation ratio (R2L1/R1L2) was
      significantly higher in Group B (1.41 +/- 0.36) than in Group A (1.06 +/- 0.20)
      (P < 0.05). CONCLUSION: We determined cholinergic dysfunction in patients with
      cognitive impairment after SAH on the basis of the pupillary response to
      tropicamide. The results provide an insight into the pathophysiology of cognitive
      impairments after SAH, which might lead to future treatment strategies.

PMID- 12234402
TI  - Oxidative damage after severe head injury and its relationship to neurological
      outcome.
AB  - OBJECTIVE: We sought to establish the time course of reactive oxygen species
      after severe head injuries in humans and to investigate their relationship with
      clinical outcomes. METHODS: Both the markers of oxidative damage-malonylaldehyde
      (MDA) and the enzymatic and nonenzymatic antioxidant defenses (i.e., superoxide
      dismutase [SOD] and vitamin E [VE], respectively)-were studied. To assess the
      time course of MDA, SOD, and VE, jugular bulb (JB) and peripheral venous blood
      samples were obtained from 30 patients within 8 hours of severe head trauma onset
      (T(0)) and 6 (T(1)), 12 (T(2)), 24 (T(3)), and 48 hours (T(4)) after trauma
      onset. Patients were divided into good and poor outcome groups according to their
      6-month neurological outcome as determined on the basis of their Glasgow Outcome
      Scale scores and biochemical profiles. RESULTS: In JB samples, MDA levels
      increased significantly at T(1), T(2), T(3), and T(4) as compared with T(0); SOD
      activity increased significantly at T(2) and T(3) as compared with T(0); and VE
      levels decreased significantly at T(1), T(2), and T(3) as compared with T(0). The
      same variables did not change significantly over time in peripheral venous blood
      samples. Moreover, the MDA levels and SOD activity detected in JB samples were
      significantly higher in the poor outcome group at T(1) and T(2). No significant
      difference in VE levels was observed between the two outcome groups. CONCLUSION:
      Reactive oxygen species-mediated oxidative damage can play an important role in
      determining the prognosis of severe brain injury in humans.

PMID- 12234403
TI  - Preoperative evaluation of neurovascular compression in patients with trigeminal
      neuralgia by use of three-dimensional reconstruction from two types of high
      resolution magnetic resonance imaging.
AB  - OBJECTIVE: To assess the value of three-dimensional (3-D) images reconstructed
      from 3-D constructive interference in steady state (3-D-CISS) and 3-D fast inflow
      with steady-state precession (3-D-FISP) images for the visualization of
      neurovascular compression in patients with trigeminal neuralgia. METHODS: Twenty
      four consecutive patients with trigeminal neuralgia underwent preoperative 3-D
      FISP and 3-D-CISS imaging. 3-D reconstruction of nerves and vessels was performed
      with the use of a volume-rendering method. We compared the 3-D reconstructed
      images with intraoperative findings. RESULTS: 3-D-CISS and 3-D-FISP images
      scanned from the same position clearly delineated the trigeminal nerve and
      vessels. 3-D reconstructed images showed the spatial relationship between the
      trigeminal nerve and causative vessels. The responsible arteries were identified
      from the 3-D reconstructed images, which closely simulated the microscopic
      operative view. CONCLUSION: 3-D reconstructions from two types of high-resolution
      magnetic resonance images (3-D-CISS and 3-D-FISP) are very useful for creating
      preoperative simulations and in deciding whether to perform surgery in patients
      with trigeminal neuralgia.

PMID- 12234404
TI  - Long-term assessment of percutaneous stereotactic thermocoagulation of upper
      thoracic ganglionectomy and sympathectomy for palmar and craniofacial
      hyperhidrosisin 1742 cases.
AB  - OBJECTIVE: We sought to determine the long-term outcome of percutaneous
      stereotactic thermocoagulation for upper thoracic ganglionectomy and
      sympathectomy in patients with palmar and craniofacial hyperhidrosis with the use
      of a three-dimensional system of coordinates for the location of the T2 and T3
      ganglia on the basis of the findings in a cadaveric study. METHODS: From November
      1986 to May 1998, upper thoracic ganglionectomy and sympathectomy with the use of
      percutaneous stereotactic thermocoagulation were performed in 1688 patients with
      palmar hyperhidrosis and 54 patients with craniofacial hyperhidrosis as
      outpatient surgical procedures based on a three-dimensional coordinate system for
      determining the location of the thermocoagulation point, which was developed by
      the authors in a cadaveric study. The technique requires only local anesthesia.
      RESULTS: After initial thermocoagulation, sweating stopped in 3465 (99.5%) of
      3484 sides. Hyperhidrosis recurred within 2 to 59 months of treatment in 268
      procedures. All patients in whom hyperhidrosis recurred were retreated
      successfully, resulting in a final success rate of 99.9%. Complications of
      treatment included pneumothorax in seven procedures (0.2%) and partial Horner's
      syndrome in five procedures (0.15%). Decreased plantar sweating was noted during
      follow-up in 92% of patients. CONCLUSION: The results of this study indicate that
      upper thoracic ganglionectomy and sympathectomy performed with the use of
      percutaneous thermocoagulation are a very effective treatment for palmar and
      craniofacial hyperhidrosis that provides excellent immediate and long-term
      results as well as a low complication rate. The method is also effective as a
      retreatment for recurrences. Our data also suggest that performing ganglionectomy
      and sympathectomy in both T2 and T3 is unnecessary, because the procedure had
      equal long-term effectiveness when performed in T2 alone.

PMID- 12234405
TI  - The transsylvian approach is "minimally invasive" but not "atraumatic".
AB  - OBJECTIVE: In light of the competition between microneurosurgery and alternative
      methods such as stereotactic radiosurgery, we tested the hypothesis that changes
      in the cerebral circulation after microneurosurgery are common among patients
      without evidence of cerebrovascular or neoplastic disease. METHODS: Blood flow
      velocities (BFVs) were recorded with transcranial Doppler ultrasonography, before
      surgery and every other day after surgery, for a group of 50 patients who
      underwent transsylvian selective amygdalohippocampectomies for treatment of
      hippocampal sclerosis. Hexamethylpropylene amine oxime-single-photon emission
      computed tomographic testing, including acetazolamide testing of cerebrovascular
      reactivity, was performed during the second postoperative week for 20 of the 50
      patients. RESULTS: BFVs in basal arteries ipsilateral to the surgical approach
      increased significantly (P < 0.001) from preoperative baseline values of
      approximately 52 +/- 13 cm/s (mean +/- standard deviation) to values of
      approximately 86 +/- 27 cm/s on postoperative Day 3 and reached their maximal
      values of approximately 115 +/- 37 cm/s after a median of 7 days. BFVs in
      contralateral vessels exhibited a similar but somewhat attenuated pattern.
      Hexamethylpropylene amine oxime-single-photon emission computed tomography
      demonstrated ipsilateral regions of hypoperfusion in 100.0% of the cases and
      contralateral hypoperfusion in 80.0%. Cerebrovascular reactivity was impaired in
      83.3% of the cases ipsilaterally and in 33.3% contralaterally. CONCLUSION: A
      significant proportion of patients who undergo microneurosurgical procedures
      develop bilateral alterations of their cerebral circulation. The elevations in
      mean BFV values represent cerebral vasospasm. Because these changes remain
      asymptomatic for the majority of patients, the transsylvian approach can be
      considered "minimally invasive" but not "atraumatic." Alternative surgical routes
      and alternative treatment modalities should be investigated in a similar manner.

PMID- 12234406
TI  - Thoracoscopic techniques for the treatment of scoliosis: early results in
      procedure development.
AB  - OBJECTIVE: The goal of this study was to determine the effectiveness of an
      endoscopic option for anterior approaches to the thoracolumbar spine for
      scoliosis treatment. Fifty patients with 24 to 45 months of follow-up data were
      retrospectively studied. Techniques for endoscopic treatment of spinal disorders
      have been under development since 1993. The benefits of thoracoscopic surgery for
      the treatment of spinal deformities have been documented as improved observation
      of the spine, enhanced access to the extremes of the curve, decreased operative
      times and blood losses, shorter hospital stays and recuperative periods, and
      decreased overall costs. After more than 150 endoscopic procedures for the
      treatment of these spinal deformities had been performed, the next step was to
      develop a thoracoscopic technique for instrumentation, correction, and fusion for
      the treatment of primary thoracic scoliosis. Our goal has been to develop a safe,
      reproducible, and effective endoscopic technique for the treatment of scoliosis
      that can provide equal or better outcomes, compared with formal open surgical
      techniques. METHODS: Between October 1996 and October 1998, 50 patients with a
      diagnosis of primary thoracic scoliosis were selected to undergo thoracoscopic
      instrumentation, correction, and fusion. Postoperatively, patients were assessed
      with respect to restoration of spinal alignment, axial derotation, pain
      management, and incidence of complications. RESULTS: Endoscopic instrumentation
      was successfully performed for all patients. Curve correction averaged 50.2%,
      improving to 68.6% in the last 10 cases. Patients with hypokyphosis averaged 20.7
      degrees of correction. The preoperative axial rotation (as measured with a
      scoliometer) averaged 16 degrees, which was corrected to 5 degrees. Postoperative
      pain was less, and patients could discontinue the use of all pain medications by
      1 to 3 weeks, compared with patients who underwent formal open procedures, who
      required pain medication for 6 to 12 weeks. The hospital stays averaged 2.9 days.
      Our initial complication rate was high, which could be attributed to the
      development of a new technique. Keys to successful fusions include total
      discectomy, complete endplate removal, and the use of autogenous bone graft.
      CONCLUSION: Although these techniques are still in early development, the initial
      results for our thoracoscopic techniques are promising. With experience, surgical
      times are decreasing and fusion and curve correction rates are improving. With
      further evolution, patients should realize shortened hospitalizations, decreased
      rehabilitation times, and decreased levels of postoperative pain. This is a
      technically demanding procedure that requires demonstrated skills in endoscopic
      discectomy and fusion.

PMID- 12234407
TI  - NeuRobot: telecontrolled micromanipulator system for minimally invasive
      microneurosurgery-preliminary results.
AB  - OBJECTIVE: Microneurosurgery can be performed less invasively with the recent
      advances in neuronavigation and neuroendoscopy. For even less invasive
      microneurosurgery, we have developed a telecontrolled micromanipulator system.
      METHODS: The NeuRobot telecontrolled micromanipulator system was developed. With
      the use of this system, surgical simulations were performed with a human
      cadaveric head. RESULTS: The system consists of four main parts, i.e., a
      micromanipulator (slave manipulator), a manipulator-supporting device, an
      operation-input device (master manipulator), and a three-dimensional display
      monitor. Three 1-mm forceps and a three-dimensional endoscope, which could be
      remotely controlled with three degrees of freedom (rotation, neck swinging, and
      forward/backward motion), were installed in the slave manipulator. All surgical
      procedures were accurately performed with this system. CONCLUSION: The use of
      telecontrolled manipulator systems in neurosurgery is very promising, and we are
      convinced that this system will facilitate more accurate, less invasive
      microneurosurgery. The details of the NeuRobot system and preliminary results are
      presented.

PMID- 12234408
TI  - Modified, multipurpose, radiolucent sugita head frame for intraoperative cerebral
      angiography.
AB  - OBJECTIVE: Although several radiolucent head-fixation devices have been developed
      to allow intraoperative cerebral angiography, no device provides satisfactory
      freedom to obtain the most suitable head position. We recently designed a
      multipurpose radiolucent Sugita head frame (modified radiolucent Sugita frame)
      with satisfactory degrees of freedom and rigidity for intraoperative head
      positioning and head holding, respectively. DESCRIPTION OF INSTRUMENTATION: A
      short arm and a ring joint, made of engineering plastic, were added to the
      prototype radiolucent Sugita frame, to permit side-tilting movements of the
      frame. The shape of all handles at the joints was also changed and the size was
      enlarged, to facilitate adjustment of the head position. EXPERIENCE AND RESULTS:
      We used this modified radiolucent Sugita frame in 20 cases involving aneurysms or
      arteriovenous malformations. The frame performed satisfactorily in all cases, in
      terms of firm head fixation and unrestrained freedom of head positioning at the
      surgeon's request. The modified radiolucent Sugita frame was evaluated with
      respect to its resistance to physical forces. The physical strength of the
      modified radiolucent Sugita frame is almost equivalent to that of the metallic
      Sugita frame and is considered sufficient for clinical usage. CONCLUSION: With
      its rigidity, satisfactory degrees of freedom, and ease of handling, the clinical
      applicability of the dramatically improved radiolucent head frame enables us to
      obtain satisfactory intraoperative angiograms.

PMID- 12234409
TI  - Anterior communicating artery aneurysms.
AB  - ANTERIOR COMMUNICATING ARTERY aneurysms are complex lesions for which surgical
      success requires extensive preoperative and intraoperative planning. Adherence to
      the tenets of aneurysm surgery, including vascular control and preservation of
      perforating arteries, is essential for their exclusion from the circulation.

PMID- 12234410
TI  - Increased expression of phosphorylated c-Jun amino-terminal kinase and
      phosphorylated c-Jun in human cerebral aneurysms: role of the c-Jun amino
      terminal kinase/c-Jun pathway in apoptosis of vascular walls.
AB  - OBJECTIVE: Vascular remodeling via apoptotic mechanisms is an important factor in
      vascular diseases. c-Jun amino-terminal kinase (JNK) is a member of the mitogen
      activated protein kinase family and initiates apoptosis mainly via
      phosphorylation of the c-Jun transcription factor. We performed this study to
      clarify the roles of the JNK/c-Jun pathway and apoptosis in the pathogenesis of
      cerebral aneurysms. METHODS: Cerebral aneurysms from 12 patients and control
      vessels from 5 patients were studied. We analyzed the expression of
      phosphorylated JNK and phosphorylated c-Jun in cerebral aneurysms by using
      immunohistochemical methods. RESULTS: Immunoreactivity for phosphorylated JNK and
      phosphorylated c-Jun was increased in the vascular walls of the cerebral
      aneurysms studied. Immunoreactivity for single-stranded deoxyribonucleic acid (a
      marker of deoxyribonucleic acid damage) was also increased in aneurysmal tissue,
      compared with control vessels, and was colocalized with that for phosphorylated
      JNK and phosphorylated c-Jun in smooth muscle cells. CONCLUSION: These
      observations may lead to better understanding of the role of the JNK/c-Jun
      pathway in the development of cerebral aneurysms and to new strategies for
      treatment.

PMID- 12234411
TI  - Activity of anti-epidermal growth factor receptor monoclonal antibody C225
      against glioblastoma multiforme.
AB  - OBJECTIVE: Overexpression of epidermal growth factor receptor (EGFR) in
      glioblastoma multiforme (GBM) secondary to EGFR gene amplification is associated
      with a more aggressive tumor phenotype and a worse clinical outcome. The purpose
      of this study was to analyze whether blocking this receptor with the anti-EGFR
      chimeric monoclonal antibody C225 would decrease proliferation and increase
      apoptosis in GBM cells. METHODS: EGFR expression and amplification were analyzed
      for seven human GBM cell lines. These lines were then exposed to different
      concentrations of C225 for 48 hours, 72 hours, and 7 days, after which time
      cytotoxicity, apoptosis, and vascular endothelial growth factor expression were
      assessed in vitro. Two EGFR-amplified human GBM were implanted in the flanks of
      nude mice, and the animals received C225 twice per week intraperitoneally for 5
      weeks. Tumor volumes and survival times were compared with those of sham-treated
      mice. RESULTS: EGFR gene amplification was demonstrated in three of the primary
      GBM lines. C225 treatment produced significant cytotoxicity in all three EGFR
      amplified GBM lines, but not in unamplified lines. Flow cytometry demonstrated
      increased apoptosis in C225-treated, EGFR-amplified GBM lines, but not in
      unamplified lines. There was a decrease in vascular endothelial growth factor
      expression in all GBM lines with exposure to C225. Tumor-bearing mice treated
      with C225 experienced significant inhibition of tumor growth as well as a 200%
      increase in median survival. CONCLUSION: Blocking EGFR in GBM cells that
      overexpress this receptor significantly changes tumor cell biology by promoting
      apoptosis while decreasing proliferation and vascular endothelial growth factor
      expression. This approach holds great promise for the treatment of patients with
      GBMs.

PMID- 12234412
TI  - Barbarian medicine in feudal Japan.
AB  - THE FIRST EUROPEANS to discover Japan were Portuguese traders who arrived in
      1542. Fifteen years later, the Portuguese Jesuit priest and surgeon Luis De
      Almeida (1525-1583) founded the first Western hospital in Japan, for the care of
      lepers, syphilitics, and orphans. Because the hospital had a negative influence
      on the spread of Christianity, the Jesuits closed it in 1586. During the Tokugawa
      Shogunate (1600-1868), when Japan was secluded from the rest of the world, the
      only foreign physicians allowed to enter Japan were those employed by the Dutch
      factory at Dejima in Nagasaki. Only four of those physicians left behind seeds
      for the foundation of Western medicine in Japan, namely Caspar Schambergen, who
      founded a Japanese school of surgery in 1650; Engelbert Kampfer, who visited
      Japan in 1691 to 1692; Carl Peter Thunberg, who botanically explored Japan in
      1775 to 1776; and Philipp Franz Balthasar von Siebold, who practiced medicine in
      Nagasaki in 1823 to 1829 and 1859 to 1861. On the whole, Western medicine and
      surgery never established a real foothold in Japan until the fall of the
      shogunate and the restoration of the emperor in 1868.

PMID- 12234413
TI  - Glossopharyngeal nerve evoked potentials after stimulation of the posterior part
      of the tongue in dogs.
AB  - OBJECTIVE: Lower cranial nerve palsy is one of the most critical complications
      after posterior fossa surgery. However, no established monitoring procedures
      exist for glossopharyngeal nerve function. Therefore, glossopharyngeal nerve
      evoked potentials after stimulation of the posterior part of the tongue in dogs
      was studied to analyze whether glossopharyngeal nerve compound action potentials
      and evoked potentials are useful in the intraoperative monitoring of patients
      undergoing brainstem and cerebellopontine angle surgery. METHODS:
      Glossopharyngeal nerve action potentials and cortical potentials were evoked by
      stimulating the posterior part of the tongue in mongrel dogs. The potentials were
      evoked by supramaximal constant current electrical stimuli delivered with bipolar
      stainless steel needle electrodes and recorded with silver ball electrodes.
      RESULTS: Compound nerve action potentials were recorded from the exposed
      intracranial portion of the glossopharyngeal nerve. The latency of the initial
      negative peak of the action potentials was 2.8 +/- 0.6 milliseconds (mean +/-
      standard deviation; n = 17). Evoked cortical potentials were recorded on the
      coronal gyrus by stimulating the contralateral side. The latencies of the initial
      positive peak and negative peak were 20.1 +/- 3.7 and 35.7 +/- 8.2 milliseconds,
      respectively (n = 6). Ipsilateral tongue stimulation elicited biphasic evoked
      potentials on the coronal gyrus, which had small amplitudes and delayed
      latencies. Both compound nerve action potentials and cortical evoked potentials
      disappeared after sectioning of the glossopharyngeal nerve. CONCLUSION: The
      glossopharyngeal nerve action potentials and cortical potentials elicited by the
      stimulation of the posterior one-third of the tongue can be recorded. These
      evoked potentials represent a new means for intraoperative monitoring of patients
      undergoing surgery in the brainstem via the cerebellopontine angle, which
      involves the lower cranial nerves.

PMID- 12234414
TI  - Effects of anti-intercellular adhesion molecule-1 antibody on reperfusion injury
      induced by late reperfusion in the rat middle cerebral artery occlusion model.
AB  - OBJECTIVE: Inflammatory processes have been implicated in the mechanisms of
      reperfusion injury. The migration of leukocytes into ischemic tissue on
      reperfusion, which involves binding to the intercellular adhesion molecule (ICAM)
      of the endothelial cell, is thought to exacerbate tissue injury. The aim of the
      present study was to assess the effects of an anti-ICAM-1 antibody on reperfusion
      induced injury after late reperfusion in a rat middle cerebral artery occlusion
      (MCAO) suture model. METHODS: The animals were divided into four groups: 1) Group
      1 (n = 7), 6 hours of permanent MCAO; 2) Group 2 (n = 7), 3 hours of MCAO
      followed by 3 hours of reperfusion; 3) Group 3 (n = 6), 6 hours of permanent MCAO
      and treatment with anti-ICAM-1 antibody (designated 1A29, 1 mg/kg) at 2 hours
      after onset of MCAO; and 4) Group 4 (n = 6), 3 hours of MCAO followed by 3 hours
      of reperfusion and 1A29 treatment. During the experiment, regional cerebral blood
      flow was measured by a laser Doppler flowmetric scanning technique. At the 6-hour
      time point, all rats were killed, and the results of leukocyte infiltration by
      myeloperoxidase activity and histological analysis using 2,3,5
      triphenyltetrazolium chloride staining were examined. RESULTS: Regional cerebral
      blood flow values before and after MCAO were not significantly different among
      the four groups. Regional cerebral blood flow values after reperfusion were not
      significantly different in the two reperfused groups. The percentage brain injury
      volumes in both the total and cortical areas and the myeloperoxidase activity in
      the latter were significantly larger in Group 2 (the reperfused group) than in
      the other groups (P < 0.05) but were decreased by anti-ICAM-1 antibody treatment
      (Group 2 versus Group 4, P < 0.05). However, there were no differences between
      Groups 1 and 3 without reperfusion. Myeloperoxidase activities correlated
      positively with infarct volumes (P < 0.01). CONCLUSION: The findings of this
      study demonstrate that the anti-ICAM antibody treatment is effective at
      inhibiting early inflammatory processes and reperfusion-induced injury caused by
      late arterial recanalization, which would contribute to widening the therapeutic
      window of thrombolytic therapy.

PMID- 12234415
TI  - Transplanted neural stem cells survive, differentiate, and improve neurological
      motor function after experimental traumatic brain injury.
AB  - OBJECTIVE: Using the neural stem cell (NSC) clone C17.2, we evaluated the ability
      of transplanted murine NSCs to attenuate cognitive and neurological motor
      deficits after traumatic brain injury. METHODS: Nonimmunosuppressed C57BL/6 mice
      (n = 65) were anesthetized and subjected to lateral controlled cortical impact
      brain injury (n = 52) or surgery without injury (sham operation group, n = 13).
      At 3 days postinjury, all brain-injured animals were reanesthetized and
      randomized to receive stereotactic injection of NSCs or control cells (human
      embryonic kidney cells) into the cortex-hippocampus interface in either the
      ipsilateral or the contralateral hemisphere. One group of animals (n = 7) was
      killed at either 1 or 3 weeks postinjury to assess NSC survival in the acute
      posttraumatic period. Motor function was evaluated at weekly intervals for 12
      weeks in the remaining animals, and cognitive (i.e., learning) deficits were
      assessed at 3 and 12 weeks after transplantation. RESULTS: Brain-injured animals
      that received either ipsilateral or contralateral NSC transplants showed
      significantly improved motor function in selected tests as compared with human
      embryonic kidney cell-transplanted animals during the 12-week observation period.
      Cognitive dysfunction was unaffected by transplantation at either 3 or 12 weeks
      postinjury. Histological analyses showed that NSCs survive for as long as 13
      weeks after transplantation and were detected in the hippocampus and/or cortical
      areas adjacent to the injury cavity. At 13 weeks, the NSCs transplanted
      ipsilateral to the impact site expressed neuronal (NeuN) or astrocytic (glial
      fibrillary acidic protein) markers but not markers of oligodendrocytes
      (2'3'cyclic nucleotide 3'-phosphodiesterase), whereas the contralaterally
      transplanted NSCs expressed neuronal but not glial markers (double-labeled
      immunofluorescence and confocal microscopy). CONCLUSION: These data suggest that
      transplanted NSCs can survive in the traumatically injured brain, differentiate
      into neurons and/or glia, and attenuate motor dysfunction after traumatic brain
      injury.

PMID- 12234416
TI  - Beyond conservatism and the boundaries of a medical discipline: a short history
      of the department of neurosurgery at kyoto university graduate school of
      medicine.
AB  - CONSTANT CHANGE AND the occasional fusion of two different entities can result in
      the creation of masterpieces, not only in art but also in neurosurgery. Chisato
      Araki is one of the pioneers of neurosurgery in Japan; his 2-year sojourn in the
      United States and Europe provided him with an extraordinary amount of experience.
      He traveled throughout the world at a time when it took 30 days to journey from
      Yokohama to New York, and he visited with most of the leading contemporary
      neurosurgeons and observed their operations, never abandoning his highly honed
      critical insights. Driven by passion and a deep sense of duty to pass on his
      knowledge and perspective, he became a beacon of hope and encouragement for young
      physicians working in a country devastated by war. His successor, Hajime Handa,
      established neurosurgery as one of the branches of neuroscience and fostered the
      collaborations and exchanges among different disciplines that have become a
      tradition and hallmark of our Department of Neurosurgery. Through anecdotes and
      glimpses of the evolution of neurosurgery at our institution, we offer insights
      into the unique nature of Japanese neurosurgery that may illuminate the path
      toward the resolution of some of the recent and enduring problems encountered in
      our specialty.

PMID- 12234417
TI  - Hypertrophic pachymeningitis as a result of a retropharyngeal inflammatory
      pseudotumor: case report.
AB  - OBJECTIVE AND IMPORTANCE: An extremely rare case of a patient with hypertrophic
      pachymeningitis that resulted from an inflammatory pseudotumor of retropharynx is
      described. CLINICAL PRESENTATION: A 59-year-old man with a 9-year history of
      retropharyngeal inflammatory pseudotumor sought care for severe headache and
      multiple cranial nerve palsies. Magnetic resonance imaging and computed
      tomographic scans revealed pachymeningeal enhancement and obstructive
      hydrocephalus attributable to marked dural thickening around the foramen magnum.
      INTERVENTION: Decompression of the foramen magnum, C1 laminectomy, and meningeal
      biopsy were performed. The histological examination of the biopsy specimen
      revealed chronic inflammatory infiltrate in the hypertrophic dura mater.
      Corticosteroid pulse therapy was subsequently completed. Clinical and
      neuroradiological findings improved remarkably. CONCLUSION: A new case of
      hypertrophic pachymeningitis as a result of a retropharyngeal inflammatory
      pseudotumor is presented. We review and discuss the clinical features and the
      pathogenic mechanisms of hypertrophic pachymeningitis.

PMID- 12234418
TI  - Ruptured aneurysm of the ophthalmic artery trunk demonstrated by three
      dimensional rotational angiography: case report.
AB  - OBJECTIVE AND IMPORTANCE: Aneurysms arising from the ophthalmic artery are
      extremely rare, compared with carotid-ophthalmic aneurysms arising from the wall
      of the internal carotid artery. We present a very unusual type of aneurysm
      arising from the ophthalmic artery itself. CLINICAL PRESENTATION: A 54-year-old
      man presented with a sudden onset of headache and was transferred to a local
      hospital. Computed tomography demonstrated subarachnoid hemorrhage around the
      left anterior clinoid process, but digital subtraction angiography failed to
      localize the source of the hemorrhage. The patient was referred to our hospital
      for further evaluation and treatment. Conventional cerebral angiography did not
      reveal the source of the hemorrhage, but three-dimensional rotational angiography
      clearly demonstrated an aneurysm arising from the ophthalmic artery trunk, apart
      from the internal carotid artery. INTERVENTION: The patient underwent
      microsurgical clipping of the aneurysm via a left pterional craniotomy. The
      aneurysm originated from the bifurcation of the ophthalmic artery and a
      perforating artery to the optic nerve. The aneurysm was successfully obliterated,
      and the postoperative course was uneventful. CONCLUSION: This report is the first
      to describe a case of a ruptured aneurysm arising from the ophthalmic artery
      trunk. We discuss the clinical significance of an aneurysm at this site, as well
      as the role of three-dimensional rotational angiography in determining the source
      of subarachnoid hemorrhage.

PMID- 12234419
TI  - Direct surgery for posttraumatic carotid-cavernous fistula as a result of an
      intradural pseudoaneurysm: case report.
AB  - OBJECTIVE AND IMPORTANCE: Traumatic carotid-cavernous fistula (CCF) is currently
      treated with interventional neuroradiological embolization procedures. A rare
      case of posttraumatic CCF that resulted from an intradural pseudoaneurysm is
      presented. The patient was treated by direct surgery because an embolization
      procedure was not suitable. CLINICAL PRESENTATION: A 16-year-old boy developed
      chemosis in the right eye 17 days after a traffic accident. Angiography revealed
      a pseudoaneurysm that arose from the site of origin of the posterior
      communicating artery, drained directly into the cavernous sinus, and formed a
      high-flow CCF. INTERVENTION: Direct surgery was performed to repair the arterial
      laceration at the junction of the internal carotid artery and the posterior
      communicating artery. A clip was applied along the internal carotid artery. The
      posterior stump of the damaged posterior communicating artery was also included
      in the clip. Postoperatively, the CCF and pseudoaneurysm were completely
      obliterated, and the symptoms were cured. CONCLUSION: Awareness of an unusual
      intradural origin of a CCF and the possibility of a direct surgical treatment
      should be kept in mind.

PMID- 12234420
TI  - Optic nerve arteriovenous malformation causing optic apoplexy: case report.
AB  - OBJECTIVE AND IMPORTANCE: Vascular malformations in the optic pathway are rare.
      Only one case of pathologically confirmed arteriovenous malformation (AVM) of the
      optic nerve has been reported previously. We document the case of a patient with
      an optic nerve AVM who presented with optic apoplexy that was diagnosed with the
      use of magnetic resonance imaging. CLINICAL PRESENTATION: A 15-year-old girl
      developed left visual disturbance of sudden onset while playing badminton. A
      magnetic resonance imaging scan disclosed left optic nerve swelling and
      intraoptical hemorrhage, although an angiogram did not reveal abnormal vessels.
      INTERVENTION: The patient underwent total removal of the hematoma and tangles of
      the abnormal vessels in the left optic nerve, which was diagnosed pathologically
      as an AVM. The patient recovered visual acuity, but the left visual field defect
      remained unchanged. CONCLUSION: Along with cavernous malformations and optic
      gliomas, AVMs can be a rare cause of optic nerve apoplexy. T2-weighted magnetic
      resonance imaging is useful in rendering the diagnosis of an optic nerve AVM,
      observed as a mass lesion consisting of serpiginous, tangled, low-intensity
      bands. Early surgical treatment is recommended to obtain a rapid recovery.

PMID- 12234421
TI  - Intrasellar pleomorphic xanthoastrocytoma: case report.
AB  - OBJECTIVE AND IMPORTANCE: A patient with a primary intrasellar pleomorphic
      xanthoastrocytoma is described. CLINICAL PRESENTATION: A 78-year-old woman
      experienced slowly progressing bilateral visual disturbance. Analysis of magnetic
      resonance imaging scans indicated a well-enhanced tumor occupying intra- and
      suprasellar spaces with displacement of the pituitary gland anteriorly.
      INTERVENTION: Partial resection of the tumor via the transsphenoidal route
      brought about improvement of the patient's visual disturbance. The tumor was
      conspicuously pleomorphic and composed of plump to spindle-shaped large and
      bizarre cells with single or multiple nuclei and lipid-laden foamy cytoplasm. The
      neoplastic cells were positive for glial fibrillary acidic protein, S-100
      protein, and vimentin. The MIB-1 antibody labeling index was very low (<1%)
      CONCLUSION: Pleomorphic xanthoastrocytoma should be included in the differential
      diagnosis of tumors arising in the posterior hypophysis.

PMID- 12234422
TI  - Basilar trunk aneurysm surgically treated with anterior petrosectomy and external
      carotid artery-to-posterior cerebral artery bypass: technical note.
AB  - OBJECTIVE: We discuss a detailed surgical technique, its indications, and
      potential pitfalls in its use. METHODS: A surgical procedure combining Kawase's
      anterior petrosectomy and external carotid artery-to-posterior cerebral artery
      high-flow bypass was performed for the treatment of a patient with a fusiform
      basilar trunk aneurysm. RESULTS: Follow-up angiography revealed the successful
      obliteration of the aneurysm and that the graft was functioning well. Late
      ischemic complications, however, occurred 5 weeks after surgery. CONCLUSION:
      Kawase's approach is a versatile option for safe vascular reconstruction of the
      posterior cerebral artery and exposure of a basilar trunk aneurysm in the upper
      clival region. Although, theoretically, a high-flow bypass might decrease the
      risk of hemodynamic ischemia, it does not prevent thromboembolic complications.

PMID- 12234423
TI  - Three-dimensional contrast medium-enhanced computed tomographic cisternography
      for preoperative evaluation of surgical anatomy of intradural paraclinoid
      aneurysms of the internal carotid artery: technical note.
AB  - OBJECTIVE AND IMPORTANCE: Precise preoperative evaluation is especially important
      when internal carotid artery aneurysms in the paraclinoid region are clipped,
      because these vascular structures are located in close proximity to various
      important structures such as the optic nerve and anterior clinoid process. We
      report a new method for "simultaneously" describing the interrelationships among
      the aneurysm, internal carotid artery, optic nerve, and bony structures with
      three-dimensional contrast medium-enhanced computed tomographic (3-D CMECT)
      cisternography. METHODS: Informed consent was obtained from the patient. An 8-ml
      injection of iotrolan (Isovist; Schering, Berlin, Germany) (240 mg I/ml) was
      administered into the lumbar intrathecal space. A computed tomographic scan of
      the head was obtained 2 hours later with a multislice Asteion computed
      tomographic scanner (Toshiba, Inc., Tokyo, Japan). An Alatoview workstation
      (Silicon Graphics, Mountain View, CA) was used to reconstruct the three
      dimensional images. RESULTS: These images, as generated by 3-D CMECT
      cisternography, were found to accurately demonstrate the interrelationships of
      the internal carotid artery, aneurysm, and surrounding structures preoperatively.
      The findings obtained from these images proved to be quite similar to the
      intraoperative findings. 3-D CMECT cisternography clarified whether the
      paraclinoid aneurysm was intradural or extradural. CONCLUSION: 3-D CMECT
      cisternography was found to provide a useful means for preoperative evaluation of
      lesions in the paraclinoid area.

PMID- 12234424
TI  - Endoscopic cranioplasty with calcium phosphate cement for pterional bone defect
      after frontotemporal craniotomy: technical note.
AB  - OBJECTIVE: Postoperative pterional depression is a minor but unpleasant sequela
      of frontotemporal craniotomy. We developed a simple method for repair of this
      condition with the use of an endoscope and calcium phosphate cement. METHODS: The
      cranial defect was approached by means of endoscopic visualization through a
      small incision within the hairline. The defect was repaired with an injectable
      calcium phosphate cement. RESULTS: The bone defect was easily accessed and
      readily repaired in all five patients. No adverse reactions to the implant were
      observed. Satisfactory cosmetic results were obtained in all patients treated
      with the use of this method. CONCLUSION: This minimally invasive cranioplasty
      technique proved to be effective for the repair of the postoperative pterional
      defect.

PMID- 12234425
TI  - History of minimally invasive spine surgery.
AB  - Patients prefer minimally invasive techniques because such techniques reduce
      recovery times and provide cosmetic benefits. Reviewing the history of minimally
      invasive surgery helps us understand the advances in spine surgery. Minimally
      invasive spine surgery has adopted techniques from several fields to better treat
      spinal disorders. Minimally invasive spine surgery has been influenced by
      advances in lasers, endoscopy, and image guidance systems. Discogenic disorders
      have been treated by using chemonucleolysis, automated percutaneous discectomy,
      and intradiscal thermoablation. Endoscopic techniques have been used to treat
      spinal disorders. Thoracoscopes and laparoscopes have been used to perform
      anterior release of scoliotic or kyphotic deformities and to perform
      transthoracic microsurgical discectomies. The role of spinal thoracoscopy has
      expanded to include corpectomy, vertebral reconstruction with internal fixation,
      hardware application, and resection of neurogenic, spinal, and paraspinal tumors.
      Advances in interbody fusion cage technology have generated a great deal of
      interest in laparoscopic techniques. Image-guided systems are widely used in
      intracranial surgery and have been adapted to facilitate screw placement since
      the middle 1990s. The use of image-guided systems for pedicle screw placement has
      improved placement accuracy. The system relies on precise localization of the
      pedicles with computed tomography. Minimally invasive surgery is designed for
      "conventional" operations involving extensive anatomic dissections performed via
      small incisions; it yields shorter recovery times and less morbidity.

PMID- 12234426
TI  - Minimally invasive spine instrumentation.
AB  - OBJECTIVE: We discuss the instrumentation used with minimally invasive spine
      surgery. METHODS: Minimally invasive surgery has revolutionized all areas of
      surgery. The use of endoscopes permits surgical maneuvers to be performed through
      small incisions. RESULTS: Video-assisted thoracoscopic surgery can be used for a
      variety of spinal indications. The nerve roots and the spinal cord can be
      decompressed, bone grafts can be placed for interbody fusion and vertebral body
      reconstruction, and internal fixation devices can be applied to stabilize the
      spine. Thoracoscopy can be used to perform thoracic sympathectomies, to resect
      thoracic disk herniations, to biopsy thoracic vertebral body lesions, to release
      complex spinal curvatures for the reduction of scoliosis, to perform
      vertebrectomies, to resect tumors, to debride infections, and to treat spinal
      fractures. Laparoscopic techniques have been applied to the lumbar spine.
      Laparoscopic procedures have been used for anterior and posterior approaches to
      the lumbar spine. Anterior arthrodesis has been performed by laparoscopic
      insertion of the Bagby and Kuslich cages into the L4-5 and the L5-S1
      intervertebral disc spaces. Laparoscopic retroperitoneal techniques have been
      used for anterior plating to fixate the anterior column rigidly to restore
      stability. In addition, the posterolateral approach has been used for pedicle
      screw fixation of the lumbar spine using endoscopic techniques. CONCLUSION:
      Minimally invasive techniques have been used successfully for treating spinal
      disorders. With the use of endoscopic techniques, a spine surgeon can perform
      complex spinal instrumentation through small portals, thus reducing morbidity for
      the patient.

PMID- 12234427
TI  - Review: complications of minimally invasive spinal surgery.
AB  - Complications of minimally invasive spinal surgery can be related to anesthesia,
      patient positioning, and surgical technique. The performance of successful
      minimally invasive spinal surgery is beset with several technical challenges,
      including the limited tactile feedback, two-dimensional video image quality of
      three-dimensional anatomy, and the manual dexterity needed to manipulate
      instruments through small working channels, which all account for a very steep
      learning curve. Knowledge of possible complications associated with particular
      minimally invasive spinal procedures can aid in their avoidance. This article
      reviews complications associated with minimally invasive spinal surgery in the
      cervical, thoracic, and lumbar spine by reviewing reported data of sufficient
      detail or with sufficient numbers of patients. In addition, possible
      complications associated with anesthesia use, patient positioning, and surgical
      techniques during thoracoscopic and laparoscopic spinal procedures are reviewed.

PMID- 12234428
TI  - Minimally invasive cervical microendoscopic foraminotomy: an initial clinical
      experience.
AB  - OBJECTIVE: We have previously reported the feasibility of using the
      microendoscopic foraminotomy (MEF) technique in a cadaveric study. We now report
      our initial clinical experience with this novel technique. METHODS: From March
      1998 to January 2001, we prospectively used the MEF technique in 25 patients with
      cervical root compression from either foraminal stenosis or disc herniation. The
      patients' demographic, clinical presentation, surgical, and outcome data were
      recorded. Another 26 patients treated via open cervical laminoforaminotomy were
      used for comparison. RESULTS: MEF cases involved less blood loss (138 versus 246
      ml per level). MEF patients recovered more rapidly, had a shorter postoperative
      stay (20 versus 68 hours), and needed fewer narcotics (11 versus 40 equivalents).
      There were two durotomies after MEF. Overall, our initial experience with the MEF
      procedure yielded symptomatic improvement for approximately 87 to 92% of
      patients, depending on which symptom was analyzed. After MEF (mean follow-up, 16
      mo; minimum follow-up, 1 year), patients with radiculopathy experienced
      resolution of their symptoms in 54%, improvement in 38%, and no change in 8% of
      cases. For open surgery, radiculopathy resolved in 48%, improved in 40%, and
      remained unchanged in 12%. For neck pain, the MEF results were 40% resolved, 47%
      improved, and 13% unchanged. Open results for neck pain were 33% resolved, 56%
      improved, and 11% unchanged. Overall, there was no significant difference in
      outcomes between the groups. CONCLUSION: The MEF technique yielded clinical
      results equivalent to those of the open surgical group as well as to those
      described in the literature. MEF patients, however, had less blood loss, shorter
      hospitalizations, and a much lower postoperative pain medication requirement.

PMID- 12234429
TI  - Anterior microforaminotomy for treatment of cervical radiculopathy: part 1--disc
      preserving "functional cervical disc surgery".
AB  - OBJECTIVE: Anterior cervical microforaminotomy was developed by the senior author
      (H-DJ) under the concept of "functional spine surgery which directly eliminates
      compressive pathological factors while preserving functional anatomic features.
      The surgical results are reported. METHODS: Among approximately 400 patients who
      underwent anterior cervical microforaminotomy at the University of Pittsburgh
      between March 1993 and May 1999, 104 patients met the inclusion criteria for this
      study. Forty-five patients were men and 59 were women. Patient ages ranged from
      26 to 74 years (median, 46 yr). Compressive pathological lesions included
      spondylotic spurs in 44 cases (42.3%), soft disc herniation in 54 cases (51.9%),
      and a combination of the two in 6 cases (5.8%). RESULTS: Eighty-three patients
      (79.8%) experienced excellent results, 20 patients (19.2%) experienced good
      results, and 1 patient experienced fair results. No patient demonstrated a poor
      or unchanged outcome. All patients demonstrated excellent decompression in their
      postoperative magnetic resonance imaging scans, and all patients except one with
      discitis maintained their motion segments well, as indicated in postoperative
      dynamic roentgenograms. Two patients developed transient Horner's syndrome, one
      patient developed transient hemiparesis, and one patient developed discitis,
      resulting in spontaneous bone fusion. CONCLUSION: Anterior microforaminotomy
      provided good or excellent outcomes, with minimal morbidities, for 98% of 104
      patients with cervical discogenic radiculopathy. The functional anatomic features
      were well preserved for 99% of the patients.

PMID- 12234430
TI  - Anterior cervical microforaminotomy for spondylotic cervical myelopathy: part 2.
AB  - OBJECTIVE: Anterior microforaminotomy for spondylotic cervical myelopathy is
      reported with surgical results. METHODS: A retrospective study was performed for
      40 patients with spondylotic cervical myelopathy who had been surgically treated
      with anterior microforaminotomy at the University of Pittsburgh between April
      1994 and June 1999. Age ranged from 32 to 74 years (median, 51 yr). Twenty-eight
      patients were men, and 12 were women. All had undergone magnetic resonance
      imaging (MRI) scans preoperatively. All underwent MRI scans and dynamic
      roentgenograms 6 weeks after the operation. The duration of follow-up ranged from
      24 months to 86 months (median, 42 mo). RESULTS: Twenty-eight patients (70%) had
      radiculopathy in addition to their myelopathy. Single-level operations were
      performed in 13 patients (32.5%), two-level operations in 19 patients (47.5%),
      three-level operations in 5 patients (12.5%), and four-level operations in 3
      patients. Eleven patients (27.5%) had excellent results, 21 patients (52.5%) had
      good results, and 8 patients (20%) had unchanged results 6 weeks after the
      operation. Thirty-five patients (87.5%) were discharged the day of or the day
      after their operation. In all patients, MRI scans revealed good anatomic
      decompression, and dynamic roentgenograms revealed good stability. Postoperative
      complications included temporary deltoid weakness in one patient and temporary
      voice fatigue in another patient. In a final survey of 30 patients, 16 patients
      (53.3%) experienced excellent results, 11 patients (36.6%) experienced good
      results, and 3 patients (10%) experienced unchanged results. Final outcome survey
      with modified Japanese Orthopedic Association score is reported in 25 patients.
      CONCLUSION: Anterior microforaminotomy provided good to excellent surgical
      results in 80% of the patients with minimal morbidities 6 weeks after the
      operation and in 90% of the patients at long-term follow-up. Spinal stability was
      well maintained in all patients.

PMID- 12234431
TI  - Endoscopically assisted transoral-transpharyngeal approach to the craniovertebral
      junction.
AB  - OBJECTIVE: We describe a series of seven consecutive patients treated with
      endoscopically assisted transoral surgery for decompression of high cervical and
      clival abnormalities. METHODS: Seven endoscopically assisted transoral procedures
      were performed at the University of Florida from September 1999 to April 2000 for
      irreducible compression at the cervicomedullary junction. The abnormalities
      encountered were primary basilar invagination from congenital craniovertebral
      junction malformation (two cases), irreducible rheumatoid cranial settling (one
      case), secondary basilar invagination caused by migration of odontoid fracture
      fragments (one case), pseudogout granulation mass (one case), clivus chordoma
      (one case), and Chiari malformation with associated basilar invagination (one
      case). RESULTS: Successful decompression was achieved in all seven patients.
      There were no adverse neurological sequelae. One patient died from a
      perioperative myocardial infarction. At a mean clinical follow-up of 6.16 months,
      neurological status was noted to be stable or improved in all remaining patients.
      CONCLUSION: Endoscopically assisted transoral surgery represents an emerging
      alternative to standard microsurgical techniques for transoral approaches to the
      anterior cervicomedullary junction. Used in conjunction with intraoperative
      fluoroscopy, it provides a safe method for anterior decompression of the
      cervicomedullary junction without the need for extensive soft palate splitting,
      hard palate resection, or extended maxillotomy. Experience is required with
      greater numbers of patients and long-term follow-up to further validate this
      promising technique.

PMID- 12234432
TI  - Thoracic, lumbar, and sacral spine anatomy for endoscopic surgery.
AB  - We discuss the anatomy of the thoracic, lumbar, and sacral levels of the spinal
      cord. Given the nature of endoscopic surgery, it is recommended that the surgeon
      have thorough knowledge not only of the bony architecture but also of important
      visceral and other soft tissue structures. It is essential to understand the
      normal anatomy to recognize the abnormal and anatomic variations. We present the
      so-called normal anatomic configurations and illustrate how these structures vary
      at the different levels of the spinal column.

PMID- 12234433
TI  - Uniportal and biportal endoscopic thoracic sympathectomy.
AB  - Sypathectomy for treatment of hyperhidrosis and pain syndromes of the upper
      extremities has recently evolved from invasive open procedures to endoscopic
      procedures. These minimally invasive techniques also have evolved, from complex
      staged procedures with multiple ports to more simplified biportal and uniportal
      procedures that require minimal tissue disruption and more limited yet effective
      sympathectomy procedures. We describe our techniques, experience, and results
      using endoscopic sympathectomy procedures with further reduced invasiveness,
      morbidity, and complications.

PMID- 12234434
TI  - Uniportal endoscopic thoracic sympathectomy for treatment of palmar and axillary
      hyperhidrosis: analysis of 2000 cases.
AB  - OBJECTIVE: Primary hyperhidrosis of the upper limbs is a common and troublesome
      condition in Taiwan. Therefore, we present our experience in treating
      hyperhidrosis via uniportal endoscopic thoracic sympathectomy. METHODS: Between
      April 1993 and March 2000, a total of 2000 patients underwent endoscopic thoracic
      sympathectomy for treatment of palmar or axillary hyperhidrosis. There were 1520
      patients with palmar hyperhidrosis and 480 patients with axillary hyperhidrosis.
      There were 788 male and 1212 female patients, with a mean age of 22.9 years
      (range, 9-60 yr). All patients were placed in a semi-sitting position, with
      single-lumen-intubation anesthesia. We performed T2 sympathectomy at the second
      and third rib beds for patients with palmar hyperhidrosis, using an 8-mm, 0
      degree, offset thoracoscope (Karl Storz GmbH & Co., Tuttlingen, Germany), via a
      0.8-cm incision below each axilla. Similar procedures were used for T3 and T4
      sympathectomies at the third, fourth, and fifth rib beds for patients with
      axillary hyperhidrosis. Questionnaires were sent to all patients after surgery.
      RESULTS: Among these 2000 patients, successful bilateral sympathectomies were
      performed for 1992 patients. The operations were usually completed within 20
      minutes (range, 10-30 min). Most patients were discharged within 4 hours after
      surgery. The surgical complications were minimal, including pneumothorax (10
      cases, 0.5%), segmental atelectasis (7 cases, 0.35%), hemothorax (2 cases, 0.1%),
      and mild wound infections (2 cases, 0.1%). There were no surgery-related deaths.
      The mean postoperative follow-up period was 51.7 months (range, 6-89 mo). A total
      of 1720 patients (86%) developed compensatory sweating of the trunk and lower
      limbs. The recurrence rates for palmar and axillary hyperhidrosis after surgery
      were 0 and 4.1% in the first year, 0.1 and 8.2% in the second year, 0.5 and 10.4%
      in the third year, 0.6 and 14.1% in the fourth year, and 1.3 and 16.7% in the
      fifth year, respectively. CONCLUSION: Uniportal endoscopic thoracic sympathectomy
      is a safe, effective method for the treatment of patients with palmar or axillary
      hyperhidrosis. For surgery, both a semi-sitting position and single-lumen
      intubation anesthesia are recommended.

PMID- 12234435
TI  - Thoracoscopic approaches to the thoracic spine: experience with 241 surgical
      procedures.
AB  - INTRODUCTION: Microsurgical thoracoscopic approaches to the thoracic spine allow
      access to the spinal cord, spinal nerves, disc spaces, vertebral bodies,
      paravertebral soft tissues, and sympathetic chain with minimal invasiveness.
      METHODS: Between January 1994 and January 2000, 241 thoracoscopic procedures were
      performed: 164 thoracic sympathectomies, 60 discectomies, 5 neurogenic tumor
      resections, 8 corpectomies and spinal reconstructions, 2 anterior releases, and 2
      biopsies. Cases were reviewed to evaluate the efficacy, surgical results, and
      complications of the thoracoscopic procedures. RESULTS: An adequate sympathectomy
      was achieved in all 164 sympathectomies. There was 100% relief of palmar and 95%
      relief of axillary hyperhidrosis. Reflex sympathetic dystrophy responded poorly
      to sympathectomy with recurrent pain. Thoracoscopic discectomy achieved complete
      decompression in 98% of patients. Gross total tumor resection was achieved in all
      five paraspinal neurogenic tumors. There was no operative mortality. Morbidity
      compared favorably with open surgical approaches to the thoracic spine.
      CONCLUSION: Thoracoscopic spinal surgery is an effective technique that provides
      full, direct access to the ventral thoracic spine. Its morbidity rate appears to
      be lower than that associated with open thoracotomy. It improves patient comfort
      and cosmetic results and shortens recovery. This technique has become the
      authors' surgical approach of choice for removing benign intrathoracic paraspinal
      neurogenic tumors and central herniated thoracic discs and for performing
      biopsies and thoracic sympathectomies. The senior author still prefers open
      surgical approaches for most thoracic corpectomies and spinal reconstruction
      procedures.

PMID- 12234436
TI  - Vertebroplasty for osteoporotic compression fractures: current practice and
      evolving techniques.
AB  - Perutaneous vertebroplasty was developed in France by Deramond et al., who
      provided initial reports of the procedure in 1987. This minimally invasive
      procedure uses a large-bore bone-cutting needle to percutaneously access a
      vertebral body, inject bone cement, and thereby stabilize and reinforce the
      remaining bone structure. The procedure was used initially to treat aggressive
      hemangiomas, but it then was extended to the treatment of osteolytic metastases
      and myeloma and currently osteoporotic compression fractures refractory to
      medical therapy. In this article, we review the current technique and its
      indications along with emerging devices and areas of current research.

PMID- 12234437
TI  - Thoracoscopic-assisted treatment of thoracic and lumbar fractures: a series of
      371 consecutive cases.
AB  - OBJECTIVE: Conventional approaches for the treatment of thoracic and
      thoracolumbar fractures require extensive surgical exposure, often leading to
      significant postoperative pain and morbidity. Thoracoscopic spinal surgery was
      performed to reduce the morbidity of these approaches while still achieving the
      primary goals of spinal decompression, reconstruction, and stabilization.
      METHODS: Between May 1996 and May 2001, 371 patients with fractures of the
      thoracic and thoracolumbar spine (T3-L3) were treated with a thoracoscopically
      assisted procedure. In the first 197 patients, a conventional open anterior
      plating system was used. The last 174 patients were treated with the MACS-TL
      system (Aesculap, Tuttlingen, Germany), which was designed specifically for
      endoscopic placement, thereby significantly reducing operative times. RESULTS:
      Seventy-three percent of the fractures were located at the thoracolumbar
      junction. In 49% of patients, mobilization of the diaphragm was performed to
      expose the fracture, with later repair. Both x-ray canal compromise and neural
      deficit were present in 15% of patients. In 35% of patients, a stand-alone
      anterior thoracoscopic reconstruction was performed. In 65% of patients, a
      supplemental posterior pedicle-screw construct was also placed either before or
      after the anterior construct. A steep learning curve was present, with an average
      operating time of 300 minutes in the first 50% of cases and an average of 180
      minutes with the MACS-TL system. The severe complication rate was low (1.3%),
      with one case each of aortic injury, splenic contusion, neurological
      deterioration, cerebrospinal fluid leak, and severe wound infection. Compared
      with a group of 30 patients treated with open thoracotomy, thoracoscopically
      treated patients required 42% less narcotics for pain treatment after the
      operation. CONCLUSION: A complete anterior thoracoscopically assisted
      reconstruction of thoracic and thoracolumbar fractures can be safely and
      effectively accomplished, thereby reducing the pain and morbidity associated with
      conventional thoracotomy and thoracolumbar approaches. Although the learning
      curve is steep, the functional and cosmetic benefits to the patient warrant the
      difficult training process.

PMID- 12234438
TI  - Extracoelomic mini approach for anterior reconstructive surgery of the
      thoracolumbar area.
AB  - OBJECTIVE: An extracoelomic mini approach is introduced as a less invasive
      technique for surgery of the thoracolumbar area performed via the anterior
      approach. METHODS: Twenty-one patients with spinal pathological findings at the
      thoracolumbar junction were assessed. The reasons for surgery were as follows:
      burst fracture of the first lumbar vertebra (n = 5), degenerative disc at L1-L2
      (n = 4), spondylodiscitis at L1-L2 (n = 8) and at T11-L1 (n = 1), pathological
      fracture of the first lumbar vertebra (n = 2), and pseudarthrosis at T11-L1 after
      failed reconstruction (n = 1). The anterior surgical procedure was performed via
      an extracoelomic mini approach. Intersomatic fusion was performed in 13 patients,
      corpectomy and bone grafting in 4, corpectomy and vertebral replacement with
      titanium cage packed with bone cement in 3, and removal of a cage in a failed
      fusion and bridging the defect with a strut bone graft in 1. Posterior
      instrumentation of the affected segment was performed in the same sitting.
      RESULTS: The mean +/- standard deviation of operative time of the anterior
      procedure was 101.2+/-36.5 minutes. The mean blood loss during the anterior
      procedure was 724 +/- 483.5 ml. The procedure was safe. No pseudarthrosis was
      encountered, and the reconstructed bone was stable in the three patients in whom
      bone cement was used. CONCLUSION: The extracoelomic mini approach is less
      invasive; it results in less incisional morbidity, and it avoids opening the
      pleural and peritoneal cavities.

PMID- 12234439
TI  - Predictors of successful outcome for lumbar chemonucleolysis: analysis of 3000
      cases during the past 14 years.
AB  - OBJECTIVE: Among numerous minimally invasive procedures for the treatment of
      herniated lumbar disc disease (HLD), chymopapain chemonucleolysis has the longest
      history of clinical usage. Long-term studies indicated good clinical results with
      a low risk for patients. However, much confusion still remains about the
      indications. This study was conducted to evaluate the predictors of successful
      outcome for chemonucleolysis and to firmly establish the proper indications for
      this procedure. METHODS: Three thousand patients with HLD were treated with
      chemonucleolysis between 1984 and 1999. The clinical success rate in our series
      was 85%. The medical history and physical and radiological findings, including
      the type and direction of disc herniation, were analyzed retrospectively.
      RESULTS: The patient group with the chief complaint of leg pain achieved a better
      clinical outcome than the patient group with low back pain (88% versus 59%, P <
      0.05). A positive straight-leg-raising test was strongly correlated with good
      clinical outcome (P < 0.05). Patients manifesting a soft, protruded disc had a
      better outcome than those manifesting diffuse bulging disc (P < 0.05). Other
      prognostic factors favoring a good outcome were as follows: young age, short
      duration of symptoms, and no bony spur or calcification on radiological study.
      CONCLUSION: Chymopapain chemonucleolysis is a safe and effective procedure.
      Proper selection of patients is important for the success of treatment. We
      propose the following three clinical criteria (Kim's triad) for selection of
      patients: chief complaint of leg pain rather than back pain, positive straight
      leg-raising test, and soft protruded disc.

PMID- 12234440
TI  - Microendoscopic lumbar discectomy: technical note.
AB  - OBJECTIVE: The microendoscopic discectomy (MED) technique was initially developed
      in 1997 to treat herniated lumbar disc disease. Since then, thousands of cases
      have been successfully performed at more than 500 institutions. This article
      discusses the technical aspects of this procedure and presents a consecutive case
      series. METHODS: A total of 150 consecutive patients underwent MED. MED is
      performed by a muscle-splitting approach using a series of tubular dilators with
      consecutively increasing diameters. A tubular retractor is then inserted over the
      final dilator, and a specially designed endoscope is placed inside the tubular
      retractor. The microdiscectomy is performed endoscopically while the surgeon
      views the procedure on a video monitor. RESULTS: Clinical outcomes were
      determined using a modified MacNab criteria, which revealed that 77% of patients
      had excellent, 17% had good, 3% had fair, and 3% had poor outcomes. The average
      hospital stay was 7.7 hours. The average return to work period was 17 days.
      Complications primarily included dural tears, which occurred in 8 patients (5%)
      and were seen early on in the patient series. Complication rates diminished as
      the surgeon's experience with this technique increased. CONCLUSION: MED for
      lumbar herniated disc disease can be performed safely and effectively, resulting
      in a shortened hospital stay and faster return to work; however, there is a
      learning curve to this procedure.

PMID- 12234441
TI  - Current concepts in minimally invasive discectomy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the various minimally
      invasive procedures available for the treatment of lumbar disc disease. METHODS:
      A review of the literature, as well as my personal experience with minimally
      invasive approaches to the lumbar discs, was performed. This review included the
      percutaneous and open surgical approaches currently available and used for the
      treatment of lumbar disc disease. RESULTS: The primary minimally invasive
      procedures for the treatment of lumbar disc disease include the following: 1)
      chemonucleolysis, introduced by Lyman Smith in 1964; 2) percutaneous manual
      nucleotomy, introduced by Hijikata in 1975; 3) microdiscectomy, first performed
      by Yasargil in 1968; 4) automated percutaneous lumbar discectomy, introduced by
      Onik in 1984; 5) laser discectomy, first performed by Ascher and Choy in 1987; 6)
      endoscopic discectomy, first used by Schreiber and Suezawa in 1986 and improved
      by Mayer, Brock, and Mathews; 7) microendoscopic discectomy, introduced by Smith
      and Foley in 1995; and 8) intradiscal electrothermy, first reported by Saal and
      Saal in 2000. CONCLUSION: Although all percutaneous techniques have been reported
      to yield high success rates, to date no studies have demonstrated any of these to
      be superior to microsurgical discectomy, which continues to be regarded as the
      standard with which all other techniques must be compared.

PMID- 12234442
TI  - Microendoscopic decompressive laminotomy for the treatment of lumbar stenosis.
AB  - OBJECTIVE: By modifying existing microendoscopic discectomy techniques, we
      previously developed a novel surgical treatment of lumbar stenosis and validated
      its ability to achieve a thorough decompression in a cadaveric study. We now
      describe our clinical experience with this new, minimally invasive
      microendoscopic decompressive laminotomy (MEDL) technique. METHODS: A MEDL was
      performed in 25 patients with classic features of lumbar stenosis. By use of a
      fluoroscopically guided percutaneous technique, the working portal was docked on
      the lamina with minimal soft-tissue injury. With the angle of the endoscope
      combined with an oblique entry, a bilateral bony and ligamentous decompression
      was achieved under the midline, thereby preserving the supraspinous-interspinous
      ligaments and contralateral musculature. A second group of 25 patients treated
      with open decompression was used for comparison. RESULTS: Effective
      circumferential decompression was achieved in the majority of patients. The
      results for the MEDL group were as follows: operative time, 109 minutes per
      single level; blood loss, 68 ml; and postoperative stay, 42 hours. The results
      for the open-surgery group were as follows: operative time, 88 minutes; blood
      loss, 193 ml; and postoperative stay, 94 hours. The MEDL group needed
      significantly less narcotic medication after surgery. Overall, 16% of the MEDL
      patients reported resolution of their back pain, 68% improved symptomatically,
      and 16% remained unchanged. The outcome of the open group was very similar.
      CONCLUSION: Compared with an equivalent open technique, MEDL appears to offer a
      similar short-term clinical outcome with a significant reduction in operative
      blood loss, postoperative stay, and use of narcotics. This lower surgical stress,
      decreased tissue trauma, and quicker recovery are particularly important in this
      elderly population of patients.

PMID- 12234443
TI  - Is laparoscopic anterior lumbar interbody fusion a useful minimally invasive
      procedure?
AB  - OBJECTIVE: Laparoscopic anterior lumbar interbody fusion (LALIF) has been
      demonstrated to be safe and effective. Its use as a standard surgical technique
      has been recommended for arthrodesis in the lumbosacral region. We reviewed our
      experience with LALIF for safety, effectiveness, and usefulness. METHODS:
      Retrospective review of 14 patients who underwent LALIF was performed. All
      patients had a diagnosis of degenerative disc disease with medically retractable
      mechanical back pain. RESULTS: No intraoperative vascular or neurological injury
      was encountered. An average operating time of 300 minutes with blood loss of 60
      ml was found. The average hospital stay was 3.4 days. At 3 to 6 months after
      surgery, 80% fusion rates were achieved. CONCLUSION: Although LALIF is a safe and
      effective procedure, it has many disadvantages, which make it a less than optimal
      procedure for routine use. Other minimally invasive approaches to the anterior
      lumbar spine result in similar beneficial results without the drawbacks
      associated with LALIF.

PMID- 12234444
TI  - Microsurgical anterior approaches to the lumbar spine for interbody fusion and
      total disc replacement.
AB  - OBJECTIVE: Anterior approaches to the lumbar spine for the treatment of various
      degenerative or postoperative abnormalities associated with low back pain have
      always been a matter of debate. They are known to be associated with considerable
      surgical trauma, high postoperative morbidity, and, occasionally, unacceptably
      high complication rates. In 1997, we inaugurated two new microsurgical
      modifications of conventional anterior approach techniques, which have been
      applied in anterior lumbar interbody fusion and more recently in total disc
      replacement. This article describes the results of microsurgical anterior
      interbody fusion in a consecutive series of 171 patients as well as preliminary
      results of these techniques for total disc replacement in 26 patients. METHODS:
      The approaches are performed with the use of a surgical microscope. Lumbar
      segments L2-L5 are exposed through a lateral retroperitoneal approach. L5-S1 can
      be reached through a midline retroperitoneal or transperitoneal approach. Both
      approaches can be performed through a limited skin incision of 4 cm. RESULTS: An
      independent observer evaluated results of anterior lumbar interbody fusion in 171
      patients during a 2-year follow-up period. The clinical follow-up demonstrated
      low perioperative and postoperative morbidity with an average blood loss of less
      than 100 ml at the fusion site. Pseudoarthrosis rates were less than 5%, and
      clinical results, as evaluated in accordance with the scoring system developed by
      Prolo et al., did not differ significantly from conventional open techniques.
      Total disc replacement through a microsurgical anterior approach seems to be a
      promising alternative to fusion procedures with even less intraoperative and
      perioperative morbidity. CONCLUSION: Microsurgical anterior approaches to the
      lumbar spine provide a reasonable surgical alternative to conventional approaches
      for anterior interbody fusion and total disc replacement.

PMID- 12234445
TI  - Minimally invasive percutaneous posterior lumbar interbody fusion.
AB  - OBJECTIVE: The wide exposure required for a standard posterior lumbar interbody
      fusion (PLIF) can cause unnecessary trauma to the lumbar musculoligamentous
      complex. By combining existing microendoscopic, percutaneous instrumentation and
      interbody technologies, a novel, minimally invasive, percutaneous PLIF technique
      was developed to minimize such iatrogenic tissue injury (MIP-PLIF). METHODS: The
      MIP-PLIF technique was validated in three cadaveric torsos with six motion
      segments decompressed and fused. Preoperative variables measured from imaging
      included interpedicular distance, pedicular height and width, interspinous
      distance, lordosis, intervertebral height, Cobb angle, and foraminal height and
      volume. Using the METRx and MD spinal access systems (Medtronic Sofamor Danek,
      Memphis, TN), bilateral laminotomies were performed using a hybrid of
      microsurgical and microendoscopic techniques. The intervertebral disc spaces were
      then distracted and prepared with the Tangent (Medtronic Sofamor Danek) interbody
      instruments. Either a 10 or 12 by 22 mm interbody graft was then placed. Using
      the Sextant (Medtronic Sofamor Danek) system, percutaneous pedicle screw-rod
      fixation of the motion segment was completed. We then applied MIP-PLIF in three
      patients. RESULTS: For segments with preoperative intervertebral/foraminal height
      loss, MIP-PLIF was effective in restoring both heights in all cases. The amount
      of improvement (9.7 to 38% disc height increase; 7.7 to 29.9% foraminal height
      increase) varied directly with the size of the graft used and the original degree
      of disc and foraminal height loss. Segmental lordosis improved by 29% on average.
      Graft and screw placement was accurate in the cadavers, except for a single Grade
      1 screw violation of one pedicle. The average operative time was 3.5 hours per
      level. In our three clinical cases, the MIP-PLIF procedure required a mean of 5.4
      hours, estimated blood loss was 185 ml, and inpatient stay was 2.8 days, with no
      intravenous narcotic use after 2 days in any of the patients. All screw and graft
      placements were confirmed. CONCLUSION: A complete PLIF procedure can be safely
      and effectively performed using minimally invasive techniques, thereby
      potentially reducing the pain and morbidity associated with standard open
      surgery. Prospective, randomized outcome studies will be required to validate the
      efficacy of this exciting new surgical technique.

PMID- 12234446
TI  - The cerebrum.

PMID- 12234447
TI  - The supratentorial arteries.

PMID- 12234448
TI  - Aneurysms.

PMID- 12234449
TI  - The cerebral veins.

PMID- 12234450
TI  - The lateral and third ventricles.

PMID- 12234451
TI  - The anterior and middle cranial base.

PMID- 12234452
TI  - The orbit.

PMID- 12234453
TI  - The sellar region.

PMID- 12234454
TI  - The cavernous sinus, the cavernous venous plexus, and the carotid collar.

PMID- 12234455
TI  - Clinical medication review by a pharmacist of patients on repeat prescriptions in
      general practice: a randomised controlled trial.

PMID- 12234456
TI  - A systematic review of effectiveness and economic evaluation of new drug
      treatments for juvenile idiopathic arthritis: etanercept.

PMID- 12234457
TI  - Application of vitamin B(12)-targeting site on Lactobacillus helveticus B-1 to
      vitamin B(12) assay by chemiluminescence method.
AB  - Lactobacillus helveticus B-1 is assumed to have a vitamin B(12)-targeting (or
      B(12)-binding) site on the cells, since the binding reaction of vitamin B(12)
      with L. helveticus B-1 cells proceeded instantly and quantitatively. This
      reaction is specific to complete B(12) compounds, cobalamins, and can be used for
      a vitamin B(12) assay method by chemiluminescence. The calibration graph was
      linear from 0.1 to 10.0 ng/mL. The B(12) contents in oyster and sardine were 75.9
      and 39.4 microg/100g, respectively. These values were very close to those
      obtained using a chemilumi-ADVIA Centaur immunoassay system with intrinsic factor
      and to those obtained by microbiological assays.

PMID- 12234458
TI  - Factors influencing cDNA microarray hybridization on silylated glass slides.
AB  - cDNA microarray technology is becoming the technique of choice for studying gene
      expression and gene expression patterns. Although experimental protocols are
      available, only limited methodological information on microarray manufacture,
      hybridization, and signal interpretation has been published. The aim of this
      paper is to provide more insight into the practical aspects of microarray
      construction and hybridization. The influence of the size, composition, and
      concentration of the spotted DNA fragments on the final hybridization signal and
      the effect of hybridization volume, sample concentration, and sample depletion
      have been tested and are discussed.

PMID- 12234459
TI  - Alexa and Oregon Green dyes as fluorescence anisotropy probes for measuring
      protein-protein and protein-nucleic acid interactions.
AB  - The fluorescence properties of Alexa 488, Oregon Green 488, and Oregon Green 514
      (Molecular Probes (Eugene, OR)) are compared when conjugated to biomolecules and
      as model compounds free in solution. We show that these relatively new, green
      fluorescence probes are excellent probes for investigation of the thermodynamics
      of protein-protein and protein-nucleic acid interactions by fluorescence
      anisotropy. Unlike fluorescein, the emission of these dyes has minimal pH
      dependence near neutrality and is significantly less susceptible to
      photobleaching. Steady-state and time-resolved fluorescence anisotropy data are
      compared for two interacting proteins of different size and for the association
      of a transcription factor with a DNA oligonucleotide containing a specific
      binding site. The temperature dependence of the fluorescence lifetimes of the
      probes is reported, and the effects of molecular size and probe motion on steady
      state anisotropy data are discussed. The critical interplay among correlation
      time, fluorescence lifetime, and the observed steady-state anisotropy is
      evaluated.

PMID- 12234460
TI  - A diagnostic tool for monitoring multidrug resistance expression in human tumor
      tissues.
AB  - Studies on multidrug resistance (MDR) require a sensitive and quantitative assay
      of mRNA expression in clinical tumor samples. Based on the small size,
      heterogenity, and the possibility of partial degradation of clinical specimens,
      unambiguous data are often difficult to obtain. The aim of the present study was
      to develop a multiplex polymerase chain reaction (PCR) in combination with nested
      PCR for quantitative analyses of mRNA expression of MDR1, MRP (multidrug
      resistance protein), and DNA topoisomerase IIalpha in small amounts of tumor
      tissue. RNA samples extracted from the human cell line RPMI 8226 and its MDR
      sublines 8226/Dox6 and DOXint40c, that overexpress MDR1 and MRP, respectively,
      were used as model substrates. In the first step, cDNAs of the three genes as
      well as of the housekeeping gene beta-actin were simultaneously amplified in
      single tubes using 20 cycles of PCR after random-primed reverse transcription.
      When necessary, a second amplification step of the preamplified PCR products was
      employed using nested primer pairs. Primer competition was evaluated by analyses
      of serially diluted amounts of cDNA and at different numbers of PCR cycles. Based
      on the results obtained, this multiplex/nested PCR approach may provide a base
      for quantitative analyses of MDR1, MRP, and topoisomerase IIalpha mRNA expression
      in clinical tumor biopsies.

PMID- 12234461
TI  - Monitoring neurotensin[8-13] degradation in human and rat serum utilizing matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - A method was developed to quantify neurotensin (NT) fragment [8-13] and a novel
      NT[8-13] derivative, KK1, in human and rat serum utilizing matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). The method
      allows for simultaneous quantification of the major NT[8-13] metabolite, NT[9-13]
      (according to molecular mass), and detection of the major KK1 metabolite, KK1M
      (according to molecular mass). The degradation rates of NT[8-13] and KK1 were
      calculated to be 24.1+/-1.0 and 193+/-8min in human serum and 5.90+/-0.22 and
      153+/-4min in rat serum, respectively. The method utilizes a novel sample drying
      technique and spectrum acquisition protocol. In addition, an internal standard
      dissimilar in structure to the analytes was used. This method may be broadly
      applicable to the quantification of NT[8-13] and other peptide analogues of
      varying structure.

PMID- 12234462
TI  - A specific enzymatic high-performance liquid chromatography method to determine N
      methyl-D-aspartic acid in biological tissues.
AB  - Recently we demonstrated that N-methyl-D-aspartic acid (NMDA) is present as an
      endogenous compound in the nervous tissues and endocrine glands of the rat where
      it plays a role in the regulation of the luteinizing hormone, growth hormone, and
      prolactin (FASEB J. 14 (2000) 699; Endocrinology 141 (2000) 3861). Based on the
      prediction that NMDA could have future importance in neuroendocrinology, we have
      devised an improved method for the specific and routine determination of NMDA in
      biological tissue. This method is based on the detection by HPLC of methylamine
      (CH(3)NH(2)) which comes from the oxidation of NMDA by D-aspartate oxidase, an
      enzyme which specifically oxidizes NMDA, yielding CH(3)NH(2) as one of the
      oxidative products of the reaction. The sensitivity of the method permits the
      accurate determination of NMDA in the supernatant of a tissue homogenate at
      levels of about 5-10 picomol/assay. However, for those tissues in which the
      concentration of NMDA is less than 1nmol/g, the sample must be further purified
      by treatment with o-phthaldialdehyde in order to separate the NMDA from the other
      amino acids and amino compounds and then concentrated and analyzed by HPLC. Using
      this method we have conducted a comparative study in order to measure the amount
      of NMDA in neuroendocrine and other tissues of various animal phyla from mollusks
      to mammals.

PMID- 12234463
TI  - Measurement of extracellular pH, K(+), and lactate in ischemic heart.
AB  - Simultaneous and continuous measurements of extracellular pH, potassium (K(+)),
      and lactate (L(-)) in ischemic rabbit papillary muscle are presented for the
      first time. Potentiometric pH and K(+) sensors and an amperometric lactate
      biosensor were used. These miniature electrodes were previously developed and
      individually tested for this purpose. The pH sensor was based on an iridium oxide
      layer electrodeposited on a planar platinum electrode fabricated on a flexible
      substrate. The potentiometric K(+) sensor was based on a polymeric membrane and
      valinomycin ionophore. The L(-) biosensor was based on lactate oxidase and an
      organic conducting salt polarized at 0.15V vs Ag/AgCl reference electrode. The
      utility of this novel analytical system to cardiovascular research was
      demonstrated by using the system to study the interrelationship of cellular K(+)
      and lactate loss in ischemic myocardium, and the role of extracellular pH and
      buffer capacity on this relationship. The results indicated: (i) sequential brief
      episodes of ischemia produced reproducible trends of L(-), pH, and K(+) changes
      during the first three episodes, (ii) extracellular L(-) increased with
      increasing buffer capacity of extracellular compartment, (iii) the patterns of
      extracellular L(-) and K(+) changes were not related directly, and (iv) L(-)
      transport and lactic acid diffusion were not the primary cause of extracellular
      acidosis during ischemia.

PMID- 12234464
TI  - Application of matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry for monitoring the digestion of phosphatidylcholine by pancreatic
      phospholipase A(2).
AB  - Different methods were established for monitoring the phospholipase A(2)(PLA(2))
      activity but all of them are rather cumbersome and time consuming. In this paper
      we have investigated the suitability of matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the
      determination of the PLA(2) activity. Phosphatidylcholine (PC) was digested with
      pancreatic PLA(2) under different conditions, i.e., various Ca(2+), PC, and
      PLA(2) concentrations. The digestion products were analyzed by MALDI-TOF MS and
      the concentration of lysophosphatidylcholine (LPC)-generated upon PLA(2)
      digestion-was determined by the application of an internal standard (known
      concentration) and by a comparison of their signal-to-noise ratios. The results
      clearly demonstrate that the LPC concentration determined from the MALDI-TOF mass
      spectra correlates directly with the activity of the applied enzyme.
      Additionally, LPC concentration increased with an increase in Ca(2+), as well as
      in the PC concentration. A single MALDI-TOF mass spectrum provides immediate
      information on the digestion products as well as on the residual substrate
      without requirements for any previous derivatization. MALDI-TOF MS can be easily
      and simply applied for monitoring the PLA(2) activity and we assume that this
      method might also be useful for other types of phospholipases.

PMID- 12234465
TI  - Flow injection fluorescence immunoassay for gentamicin using sol-gel-derived
      mesoporous biomaterial.
AB  - Sol-gel-derived mesoporous biomaterials were used for the first time in the flow
      injection fluorescence immunoassay system. Anti-gentamicin antibody was
      immobilized in a mesoporous sol-gel material using tetramethoxysilane as a
      precursor and poly(ethylene glycol) as a template. The sol-gel glass was used to
      develop an immunoaffinity column for the flow-injection immunoassay of
      gentamicin. Little unspecific adsorption of gentamicin on the sol-gel and no
      antibody leaching under harsh elution conditions were found. The immunoassay is
      based on the competition between gentamicin and fluorescein isothiocyanate
      labeled gentamicin for a limited number of encapsulated antibody binding sites.
      NaOH solution of 5 x 10(-3)mol/L is used for the regeneration of encapsulated
      antibody binding sites after each measurement, which allows the immunoreactor to
      be used for up to 20 times without any loss of reactivity. Sample
      preconcentration is not needed and a single assay can be performed within 10 min.
      The calibration for gentamicin has a working range of 250-5000 ng/mL with a
      detection limit of 200 ng/mL, which is close to that of the fluorescence
      immunoassay and fluorescence polarization immunoassay using the same reactants.
      Comparison of the results from this method with that obtained from HPLC showed an
      excellent correlation.

PMID- 12234467
TI  - Direct quantification of human serum albumin in human blood serum without
      separation of gamma-globulin by the total internal reflected resonance light
      scattering of thorium-sodium dodecylbenzene sulfonate at water/tetrachloromethane
      interface.
AB  - A direct quantification of human serum albumin (HSA) in blood serum samples
      without separation is proposed based on the measurements of total internal
      reflected resonance light scattering (TIR-RLS) at water/tetrachloromethane
      (H(2)O/CCl(4)) interfaces. In the pH range of 6.37-6.59, the coadsorption of the
      binary complex of HSA-Th(IV) with sodium dodecylbenzene sulfonate occurs at the
      H(2)O/CCl(4) interface, forming an amphiphilic layer and displaying greatly
      enhanced TIR-RLS signals with the maximum peak located at 340-370 nm. The
      enhanced TIR-RLS intensity is in proportion to the HSA concentration in the range
      0.15-1.0 micro gml(-1). The limit of detection is 14.4 ngml(-1). The contents of
      HSA in blood serum samples were determined with the recovery of 97.1-102.3% and
      RSD of 0.6-2.9%, which are identical to those obtained according to the
      spectrofluorimetric method using chrome azurol S.

PMID- 12234466
TI  - Development of an assay and determination of kinetic parameters for chondroitin
      AC lyase using defined synthetic substrates.
AB  - Many techniques have been developed for the assay of polysaccharide lyases;
      however, none have allowed the measurement of defined and reproducible k(cat) and
      K(m) values due to the inhomogeneous nature of the polymeric substrates. We have
      designed three different substrates for chondroitin AC lyase from Flavobacterium
      heparinum that can be monitored by three different techniques: UV/Vis
      spectroscopy, fluorescence spectroscopy, and use of a fluoride ion-selective
      electrode. Each is a continuous assay, free from interferences caused by other
      components present in crude enzyme preparations, and allows meaningful and
      reproducible kinetic parameters to be determined. The development of these
      defined synthetic substrates has opened up a wide variety of mechanistic studies
      that can be performed to elucidate the detailed catalytic mechanism of this, and
      other, polysaccharide lyases. The application of these techniques, which include
      kinetic isotope effects and linear free energy analyses, was not possible with
      the previous polymeric substrates and will allow this relatively poorly
      understood class of polysaccharide-degrading enzymes to be studied
      mechanistically.

PMID- 12234468
TI  - Analysis of Cre-loxP interaction by surface plasmon resonance: influence of
      spermidine on cooperativity.
AB  - To study target site selectivity of one important class of DNA-binding proteins,
      site-specific DNA recombinases, we developed an automated real-time kinetic assay
      based on surface plasmon resonance (BIACORE) and formulated a curve-fitting model
      that takes into account cooperative interactions. Monitoring the interaction
      between the Cre DNA recombinase and its specific target site loxP by BIACORE, we
      found that Cre associates with loxP tightly and highly cooperatively. We observed
      that the cooperative moment of the Cre-loxP interaction is strongly dependent on
      the concentration of spermidine, a small polyamine influencing DNA conformation.
      Thus, DNA conformation can have a profound impact on substrate recognition and
      subsequent recombination.

PMID- 12234470
TI  - Measurement of adenylyl cyclase by separating cyclic AMP on silica gel thin-layer
      chromatography.
AB  - A procedure for isolation of cyclic AMP (cAMP) by thin-layer chromatography on
      silica gel is described. One-dimensional ascending chromatograms were developed
      using [H(2)O/C(2)H(5)OH/NH(4)HCO(3) (30%:70%:0.2M)] as the mobile phase. This
      procedure separated [32P]cAMP from other radioactive metabolites of [32P]ATP in
      up to 19 samples on one sheet (20 x 10 cm) over 40-60 min at room temperature (21
      degrees C). This simple and rapid isolation method provides a novel and
      convenient technique for the assay of adenylyl cyclase.

PMID- 12234469
TI  - A continuous 96-well plate spectrophotometric assay for branched-chain amino acid
      aminotransferases.
AB  - A new, continuous 96-well plate spectrophotometric assay for the branched-chain
      amino acid aminotransferases is described. Transamination of L-leucine with alpha
      ketoglutarate results in formation of alpha-ketoisocaproate, which is reductively
      aminated back to L-leucine by leucine dehydrogenase in the presence of ammonia
      and NADH. The disappearance of absorbance at 340 nm due to NADH oxidation is
      measured continuously. The specific activities obtained by this procedure for the
      highly purified human mitochondrial and cytosolic isoforms of BCAT compare
      favorably with those obtained by a commonly used radiochemical procedure, which
      measures transamination between alpha-ketoiso[1-14C]valerate and L-isoleucine.
      Due to the presence of glutamate dehydrogenase substrates (alpha-ketoglutarate,
      ammonia, and NADH) and L-leucine (an activator of glutamate dehydrogenase) in the
      standard assay mixture, interference with the measurement of BCAT activity in
      tissue homogenates by glutamate dehydrogenase is observed. However, by limiting
      the amount of ammonia and including the inhibitor GTP in the assay mixture, the
      interference from the glutamate dehydrogenase reaction is minimized. By comparing
      the rate of loss of absorbance at 340 nm in the modified spectrophotometric assay
      mixture containing leucine dehydrogenase to that obtained in the modified
      spectrophotometric assay mixture lacking leucine dehydrogenase, it is possible to
      measure BCAT activity in microliter amounts of rat tissue homogenates. The
      specific activities of BCAT in homogenates of selected rat tissues obtained by
      this method are comparable to those obtained previously by the radiochemical
      procedure.

PMID- 12234471
TI  - The determination of homocysteine-thiolactone in biological samples.
AB  - Homocysteine-thiolactone, a cyclic thioester of homocysteine, is synthesized by
      methionyl-tRNA synthetase in all cell types. A new assay for the determination of
      homocysteine-thiolactone in biological samples is described. The assay involves
      separation of homocysteine-thiolactone from macromolecules by ultrafiltration.
      Homocysteine-thiolactone is further purified and quantified by high-pressure
      liquid chromatography either on a reverse phase or a cation exchange micro-bore
      column. The detection and quantitation are obtained by monitoring the absorbance
      at 240 nm, a maximum in a UV spectrum of homocysteine-thiolactone. The
      sensitivity of detection is 5 pmol. This assay has been applied to bacteria
      (Escherichia coli and Mycobacterium smegmatis), the yeast Saccharomyces
      cerevisiae, cultured human vascular endothelial cells, and human plasma. The data
      support the conclusion that homocysteine-thiolactone is a ubiquitous metabolite
      whose levels are directly related to homocysteine levels.

PMID- 12234472
TI  - Detection of polymorphisms at exons 3 (Tyr113-->His) and 4 (His139-->Arg) of the
      microsomal epoxide hydrolase gene using fluorescence PCR method combined with
      melting curves analysis.
AB  - An association between exon 3 polymorphisms of the gene encoding microsomal
      epoxide hydrolase (mEH) and susceptibility to the development of chronic
      obstructive pulmonary disease (COPD) has been described. We have developed two
      methods for detecting polymorphisms at exons 3 (Tyr113-->His) and 4 (His139-
      >Arg) of the mEH gene based on different melting temperatures (T(m)) of
      fluorescent-labeled oligonucleotide hybridization probes using single-step assays
      that combine fluorescence PCR and melting curve analysis (LightCycler
      methodology). DNA was extracted from blood in 79 COPD patients and 146 healthy
      controls. Results were compared with those obtained by restriction fragment
      length polymorphism (RFLP) analysis to detect Tyr113His variants and a single
      strand conformation polymorphism (SSCP) assay for His139Arg detection. The T(m)
      of the exon 3 polymorphisms were 61.3 degrees C for Tyr113 (wild type) and 67.5
      degrees C for His113 (mutant). The T(m) values of the exon 4 polymorphisms were
      67.5 degrees C for His139 (wild type) and 59.2 degrees C for Arg139 (mutant). The
      within- and between-run melting peaks for the same allele differed by less than
      0.5 degrees C for both the exon 3 and the exon 4 polymorphisms. Thus, melting
      analysis allowed easy and unambiguous assignment of genotyping by means of the
      respective melting curves. The proportion of individuals who were homozygous
      mutant for exon 3 was significantly higher in the COPD group than in the control
      group (p=0.004). LightCycler fluorescence genotyping of exon 4 polymorphisms
      correlated perfectly with SSCP results. RFLP assay classified 2 patients as
      homozygous mutant while LightCycler analysis genotyped them as heterozygous. DNA
      analysis by PCR and sequencing confirmed the LightCycler result. These high-speed
      (about 40 min for 32 samples), highly sensitive, and specific small-volume assays
      with low labor requirements hold great promise as tools for rapid detection of
      COPD susceptibility.

PMID- 12234473
TI  - Microplate gel-filtration method for radioligand-binding assays.
AB  - A thin-layer gel-filtration chromatographic method has been developed in a 96
      well format to separate free and protein-bound ligand in radioligand-binding
      assays. The mobile phase in the gel-filtration plate is removed via quick
      centrifugation before samples are applied. Protein-bound ligand is recovered via
      centrifugation into another 96-well plate for radioactivity measurements. The
      method exhibits excellent recovery of protein-ligand complexes and less
      opportunity for dissociation of the complexes since it eliminates major dilution
      effects from the mobile phase of a column and from elution steps in conventional
      gel-filtration chromatography. It offers other advantages: simple, rapid,
      inexpensive, quantitative, and able to handle a large number of samples as
      required in drug discovery and clinical settings. This microplate gel-filtration
      method was optimized in studies of receptor-ligand interactions using estrogen
      receptors as examples and can be used in other radioligand-binding assays.

PMID- 12234474
TI  - Synthesis and conformational studies of a transmembrane domain from a diverged
      microsomal Delta(12)-desaturase.
AB  - Transmembrane domains of the acyl-coenzyme A and acyl phosphatidylcholine
      utilizing desaturases may control interactions with electron transport domains,
      be involved in substrate specificity and/or serve as a structural foundation for
      the enzyme. To experimentally define these domains and as a prelude to detailed
      NMR studies, a segment of the microsomal Delta(12)-desaturase/acetylenase CREP-1
      predicted to contain the amino-proximate transmembrane domain TM-A was chemically
      synthesized. A modified 9-fluorenylmethoxycarbonyl procedure was used that
      ensured complete deprotections at each homologation and the peptide was purified
      in good yield by reverse-phase high-performance liquid chromatography.
      Conformational studies of the hydrophobic peptide TM-A demonstrated its strong
      propensity for folding into an alpha-helical secondary structure. The helical
      content was 58-65% in aqueous solutions containing 40-80% 2,2,2-trifluoroethanol,
      a lipomimetic solvent, and was maximal at low temperatures. The peptide assumed a
      largely helical character when incorporated into phospholipid bilayers and
      detergent micelles. Experimental evidence is in agreement with neural network
      predictions that a transmembrane domain exists between residues R-44 and I-67 in
      this diverged Delta(12)-desaturase.

PMID- 12234475
TI  - Electrochemistry and electrocatalysis with heme proteins in chitosan biopolymer
      films.
AB  - Protein-chitosan (CS) films were made by casting a solution of proteins and CS on
      pyrolytic graphite electrodes. Myoglobin (Mb), hemoglobin (Hb), and horseradish
      peroxidase (HRP) incorporated in CS films gave a pair of stable, well-defined,
      and quasi-reversible cyclic voltammetric peaks at about -0.33V vs saturated
      calomel electrode in pH 7 buffers, respectively, while catalase (Ct) in CS films
      showed a peak pair at about -0.46V which was not stable. All these peaks are
      located at the potentials characteristic of heme Fe(III)/Fe(II) redox couples of
      the proteins. The electrochemical parameters such as formal potentials (E degrees
      (')) and apparent heterogeneous electron-transfer rate constants (k(s)) were
      estimated by square-wave voltammetry with nonlinear regression analysis. Chitosan
      films contained considerable water and formed hydrogel in aqueous solution.
      Positions of the Soret absorbance band suggest that Mb and Hb in CS films keep
      their secondary structure similar to the native states in the medium pH range,
      while HRP and Ct retain their native conformation at least in the dry CS films.
      Scanning electron microscopy of the films demonstrated that interaction between
      the proteins and CS would make the morphology of dry protein-CS films very
      different from the CS films alone. Oxygen, trichloroacetic acid, nitrite, and
      hydrogen peroxide were catalytically reduced by all four proteins in CS films.

PMID- 12234476
TI  - Comparative measurements of multicomponent phospholipid mixtures by electrospray
      mass spectroscopy: relating ion intensity to concentration.
AB  - Electrospray mass spectrometry allows direct identification and sensitive
      detection of multiple phospholipids in non-derivatized cell extracts. However,
      quantitative analyses are not straightforward, and are confounded by analyte and
      mass discrimination effects, and non-linear dependence of the ion intensity on
      concentration. This non-linearity is particularly severe in the negative mode and
      precludes even comparative measurements of anion concentrations. Herein, we
      report a general method for relating negative electrospray ion intensity to
      concentration when analyzing multicomponent phospholipid samples. In this method,
      the intensity of individual ions is measured at several different concentrations
      of the total mixture and the slope (n(E)) of the double log plot of sample
      concentration vs. intensity for each analyte is determined. The n(E) is then used
      to map intensity data to a quantity proportional to concentration for each
      analyte. The method allows facile and accurate comparison of negative spectra of
      complex mixtures containing structurally different anions.

PMID- 12234477
TI  - A fluorescence-based high performance liquid chromatographic method for the
      characterization of palmitoyl acyl transferase activity.
AB  - Although protein palmitoylation is essential for targeting many important
      signaling proteins to the plasma membrane, the mechanism by which palmitoylation
      occurs is uncharacterized, since the enzyme(s) responsible for this modification
      remain unidentified. To study palmitoyl acyl transferase (PAT) activity, we
      developed an in vitro palmitoylation (IVP) assay using a fluorescently labeled
      substrate peptide, mimicking the N-terminal palmitoylation motif of proteins such
      as non-receptor Src-related tyrosine kinases. The palmitoylated and non
      palmitoylated forms of the peptide were resolved by reverse-phase HPLC and
      detected by fluorescence. The method was optimized for PAT activity using lysates
      from the MCF-7 and Hep-G2 human tumor cell lines. The PAT activity was inhibited
      by boiling, reducing the incubation temperature, or adding 10 microM 2
      bromopalmitate, a known palmitoylation inhibitor. This IVP assay provides the
      first method that is suitable to study all facets of the palmitoylation reaction,
      including peptide palmitoylation by PAT(s), depalmitoylation by thioesterases,
      and evaluation of potential palmitoylation inhibitors.

PMID- 12234478
TI  - Quantitative high-performance liquid chromatography/electrospray ionization
      tandem mass spectrometric analysis of 2- and 3-series prostaglandins in cultured
      tumor cells.
AB  - This paper describes a rapid and simple technique for the simultaneous
      quantitative analysis of PGE(2), PGE(3), and other closely related prostaglandins
      from cultured cells using liquid chromatography/electrospray ionization tandem
      mass spectrometry. This method permits quantification of selected individual
      prostaglandins derived either from arachidonic acid (AA) or eicosapentaenoic acid
      (EPA) from cell extracts without tedious derivatization, lengthy sample
      preparation, and separation required by GC-MS- or HPLC-UV-based methods. The
      validation assessment showed that the quantitative determination is linear
      (r(2)>0.999) for both PGE(2) and PGE(3) in the range tested (1-500 ng/ml, 0.0028
      1.4 microM) and a coefficient of variation lower than 10% was obtained for
      samples analyzed on 3 separate days. The detection limit was 2.5 pg for both
      PGE(2) and PGE(3). Extraction efficiency of PGE(2) and PGE(3) from cell
      suspensions ranged from 89.4 to 98.2%. As an application of the method,
      prostaglandins formed by EPA in human lung cancer A549 cells were determined. A
      62% reduction of PGE(2) formation was noted when A549 cells were treated with 10
      microM of EPA. Concomitantly, EPA increased formation of PGE(3) by 10-fold in
      A549 cells. This is the first report that unequivocally demonstrates that EPA can
      be converted to PGE(3) by cyclooxygenase in human cancer cells.

PMID- 12234479
TI  - A modified kynurenine bioassay for quantitative determination of human interferon
      gamma.

PMID- 12234480
TI  - Variable estimation of genomic DNA methylation: a comparison of methyl-CpG
      binding domain column chromatography and bisulfite genomic sequencing.

PMID- 12234481
TI  - Stopped-flow fluorescence method for the detection of heme degradation products
      in solutions of chemically modified hemoglobins and peroxide.

PMID- 12234482
TI  - Be careful with the primers when screening your clones by polymerase chain
      reaction.

PMID- 12234483
TI  - Effects of choice of reverse-transcriptase enzyme and use of T4 gene 32 protein
      on banding patterns in agarose gel differential display.

PMID- 12234484
TI  - Structure-function relationship exists for ginsenosides in reducing cell
      proliferation and inducing apoptosis in the human leukemia (THP-1) cell line.
AB  - Ginsenosides of the 20(S)-protopanaxadiol and 20(S)-protopanaxatriol
      classifications including the aglycones, protopanaxadiol (PD), protopanaxatriol
      (PT), and ginsenosides Rh2 and Rh1 were shown to posses characteristic effects on
      the proliferation of human leukemia cells (THP-1). A similar efficacy was not
      apparent for ginsenoside Rg3. The concentrations to inhibit 50% of cells (LC50)
      for PD, Rh2, PT, and Rh1 were 13, 15, 19, and 210 microg/mL, respectively. PD and
      PT induced DNA fragmentation at the LC50 after 72 h of treatment, compared to
      Rh2, Rh1, dexamethasone, and untreated cells. Cell-cycle analysis confirmed
      apoptosis with PD and PT treatment of THP-1 cells resulting in a buildup of sub
      G1 cells after 24, 48, and 72 h of treatment. Rh2 and dexamethasone treatments
      also increased apoptotic cells after 24 h, whereas Rh1 did not. After 48 and 72
      h, Rh2, Rh1, and dexamethasone similarly increased apoptosis, but these effects
      were significantly (P<0.05) lower than those observed for both PD and PT
      treatments. Furthermore, treatments that produced the largest buildup of
      apoptotic cells were also found to have the largest release of lactate
      dehydrogenase. It can be concluded from these studies that the presence of sugars
      in PD and PT aglycone structures reduces the potency to induce apoptosis, and
      alternately alter membrane integrity. These cytotoxic effects were different to
      THP-1 cells than dexamethasone.

PMID- 12234485
TI  - Structural features associated with the binding of glutamine-containing peptides
      to Factor XIII.
AB  - Activated Factor XIII a2 catalyzes the formation of intermolecular gamma-glutamyl
      epsilon -lysyl cross-links in the fibrin network. Solution NMR studies were
      carried out to characterize, the structural features associated with the binding
      of glutamine-containing peptides to Factor XIII. A coupled uv/vis kinetic assay
      demonstrated that K9 peptide (1-10), alpha2-antiplasmin (1-15), and alpha2
      antiplasmin (1-15 Q4N) all function as glutamine-containing substrates for
      activated Factor XIII a2. 2D TOCSY spectra of the peptides exhibit upfield
      chemical shifts for the glutamine protons in the presence of Factor XIII. These
      results indicate that the reactive peptide glutamines are encountering a
      distinctive environment within the Factor XIII active site. 1D proton line
      broadening and 2D transferred-NOESY studies reveal that the glutamines and
      residues located C-terminally come in direct contact with the enzyme and adopt an
      extended conformation. Substrates with sequences similar to alpha2-antiplasmin (1
      15) are proposed to bind both at the catalytic site and at a neighboring apolar
      region.

PMID- 12234486
TI  - Enzymatic properties and regulation of ZPU1, the maize pullulanase-type starch
      debranching enzyme.
AB  - Starch debranching enzymes (DBE) are required for mobilization of carbohydrate
      reserves and for the normal structural organization of storage glucan polymers.
      Two isoforms, the pullulanase-type DBEs and the isoamylase-type DBEs, are both
      highly conserved in plants. To address DBE functions in starch assembly and
      breakdown, this study characterized the biochemical activity of ZPU1, a
      pullulanase-type DBE that is the product of the maize Zpu1 gene. Assays showed
      directly that recombinant ZPU1 (ZPU1r) expressed in Escherichia coli functions as
      a pullulanase-type enzyme, and 1H-NMR spectroscopy demonstrated that ZPU1r
      specifically hydrolyzes alpha(1-->6) branch linkages. Preferred substrates for
      ZPU1r hydrolytic activity were determined, as were pH, temperature, and thermal
      stability optima. Kinetic properties of ZPU1r with respect to two substrates,
      beta-limit dextrin and pullulan, were determined. ZPU1 activity was increased by
      incubation with thioredoxin h, and native activity was decreased in mutants that
      accumulate soluble sugars, suggesting potential regulatory mechanisms.

PMID- 12234487
TI  - Nitric oxide and protein nitration in the cystic fibrosis airway.
AB  - Cystic fibrosis (CF), characterized by chronic airway infection and inflammation,
      ultimately leads to respiratory failure. Exhaled nitric oxide (NO), elevated in
      most inflammatory airway diseases, is decreased in CF, suggesting either
      decreased production or accelerated metabolism of NO. The present studies
      performed on two groups of CF patients provide further support for a disordered
      NO airway metabolism in CF respiratory tract disease. Despite confirmation of
      subnormal NOS2 in the CF airway epithelium, alternative isoforms NOS1 and NOS3
      were present, and inflammatory cells in the CF airway expressed abundant NOS2.
      Increased immunohistochemical staining for nitrotyrosine was demonstrated in lung
      tissues from patients with CF as compared to control. To our knowledge, this is
      the first report localizing nitrotyrosine in diseased CF lung tissue. While the
      relative NOS2 deficiency in CF respiratory tract epithelium may contribute to the
      lower expired NO levels, these results suggest that increased metabolism of NO is
      also present in advanced CF lung disease. The significance of altered NO
      metabolism and protein nitration in CF remains to be fully elucidated.

PMID- 12234488
TI  - Cocoa extract protects against early alcohol-induced liver injury in the rat.
AB  - Oxidants have been shown to be involved in alcohol-induced liver injury. This
      study was designed to determine whether cocoa flavonoid extract, composed mostly
      of epicatechin and epicatechin oligomers, protects against early alcohol-induced
      liver injury in rats. Male Wistar rats were fed high-fat liquid diets with or
      without ethanol (10-14 g/kg per day) and cocoa extract (400 mg/kg per day)
      continuously for 4 weeks using an enteral feeding protocol. Mean body weight
      gains ( approximately 4 g/day) were not significantly different between treatment
      groups. Cocoa extract did not affect average daily urine ethanol concentrations (
      approximately 200mg/dL). After 4 weeks, serum alanine amino transferase levels of
      the ethanol group were increased nearly fourfold (110+/-16 IU/L) compared to
      control values (35+/-3 IU/L); this effect of ethanol was blocked by cocoa extract
      (60+/-6 IU/L). Additionally, enteral ethanol caused severe fat accumulation, mild
      inflammation, and necrosis in the liver; cocoa extract significantly blunted
      these changes. Increases in liver TNFalpha protein levels caused by ethanol were
      completely blocked by cocoa extract. Further, ethanol significantly increased the
      accumulation of protein adducts of 4-hydroxynonenal, a product of lipid
      peroxidation serving as an index of oxidative stress; again this was counteracted
      by the addition of cocoa extract. These results indicate that dietary flavanols
      such as those found in cocoa can prevent early alcohol-induced liver injury.

PMID- 12234489
TI  - Mutations of the WD repeats that compromise Tup1 repression function maintain
      structural integrity of the WD domain trypsin-resistant core.
AB  - The yeast global transcriptional repressor Tup1 contains 7 WD repeats in its C
      terminus that form a beta-propeller-like structure, in which the first and last
      WD repeats interact to make a closed circle. The WD domains of all proteins
      tested, including Tup1, form a compact structure resistant to trypsin digestion
      (Garcia-Higuera et al., Biochemistry 35 (1996) 13985-13994). We found that the in
      vitro formation of the trypsin-resistant core of Tup1 requires just five WD
      repeats (WD2-6). Deletion of the ST region between WD1 and WD2 destabilizes the
      trypsin-resistant core, but maintains Tup1 repression function in vivo. Linker
      insertion and point mutations in the WD repeats that compromise Tup1 repression
      function in vivo still maintain the trypsin-resistant core in vitro These results
      indicate that structural perturbation of the WD domain structure cannot explain
      the effects of these mutations on Tup1 repression function.

PMID- 12234490
TI  - The mechanism of inhibition of the sarco/endoplasmic reticulum Ca2+ ATPase by
      paxilline.
AB  - Paxilline, an indole alkaloid mycotoxin from Penicillium paxilli, is an inhibitor
      of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). Paxilline inhibited
      differing isoforms of SERCA with IC50s between 5 and 50 microM. It inhibited more
      potently the purified Ca2+ ATPase activity from skeletal muscle with an IC50 of 5
      microM. Detailed effects of this inhibitor on the Ca2+ and ATP dependence upon
      activity indicate that it affects the high-affinity Ca2+-binding (E1) form of the
      ATPase. In addition, paxilline is a "competitive" inhibitor with respect to high
      concentrations of ATP, increasing the regulatory binding site K(m), without
      affecting the catalytic binding site K(m). At higher concentrations, paxilline
      inhibits phosphoenzyme formation from ATP and inorganic phosphate, without
      affecting nucleotide binding. We therefore suggest that paxilline has two effects
      on the Ca2+ ATPase. At lower concentrations (5-10 microM), paxilline inhibits the
      ATP-dependent acceleration of Ca2+ release from the phosphoenzyme and/or
      phosphoenzyme decay. At higher concentrations, paxilline inhibits phosphoenzyme
      formation.

PMID- 12234491
TI  - Mechanisms of vanadate-induced cellular toxicity: role of cellular glutathione
      and NADPH.
AB  - Besides its insulin-mimetic effects, vanadate is also known to have a variety of
      physiological and pharmacological properties, varying from induction of cell
      growth to cell death and is also a modulator of the multidrug resistance
      phenotype. However, the mechanisms underlying these effects are still not
      understood. The present report analyzes the mechanisms of vanadate toxicity in
      two cell lines previously found to have different susceptibilities to this
      compound. It was shown that catalase and GSH reversed the sensitivity of a
      vanadate-sensitive cell line and NADPH sensitized vanadate-resistant cells. NADPH
      also increased the residues of P-Tyr and the induction of Ras protein expression
      in vanadate-resistant cells, while GSH avoided these effects in vanadate
      sensitive cells. Thus, it seems that the effects of vanadate in signal
      transduction are dependent on NADPH and are related to cell death. Based on the
      effects observed in the present study it was suggested that once inside the cell,
      vanadate is reduced to vanadyl in a process dependent on NADPH. Vanadyl then may
      react with H2O2 generating primarily peroxovanadium species (PV) rather than
      following the Fenton reaction. The PV compounds formed would be responsible for P
      Tyr increase, Ras induction, and cell death. The results obtained also point to
      vanadate as a possible chemotherapic in the use of multidrug-resistant tumors.

PMID- 12234492
TI  - Kinetic studies of guanine recognition and a phosphate group subsite on
      ribonuclease T1 using substitution mutants at Glu46 and Lys41.
AB  - pH-Dependent kinetic studies were performed with ribonuclease T1 (RNase T1) and
      its Glu46Ser, Lys41Met, and Lys41Thr mutants with GpC and polyinosinic acid
      (PolyI) as substrates. Plots of pH versus log(k(cat)/K(M)) for both substrates
      had ascending slopes that were significantly greater for RNase T1 compared with
      Glu46Ser-RNase T1, which indicated that the gamma-carboxyl group of conserved
      Glu46 must be deprotonated (anionic) for maximal interaction with N1H and N2H of
      the guanine moiety of GpC or the N1H of the hypoxanthine moiety of PolyI. The
      involvement of the epsilon -ammonium group of nonconserved Lys41 at the 2p
      subsite (i.e., for an RNA phosphate group two nucleotide positions 5'-upstream
      from the active site) was supported by comparisons of Lys41Met-RNase T1 and
      Lys41Thr-RNase T1 with wild-type. These mutants shared identical catalytic
      properties (i.e., k(cat) and K(M)) with wild-type using GpC as a substrate.
      However, k(cat)/K(M) for both were identical with each other but lower than those
      for wild-type when PolyI was the substrate (PolyI has a phosphate group that
      could interact at a putative 2p site). The pH dependence of this latter
      difference can be interpreted as reflecting the loss of the 2p subsite
      interaction with the wild-type enzyme upon deprotonation of the epsilon -ammonium
      group of Lys41. Subsite interactions for ribonucleases are shown to mainly
      increase k(cat) and result in an attenuated pH dependence of k(cat)/K(M).

PMID- 12234493
TI  - Interactions of lipoic acid radical cations with vitamins C and E analogue and
      hydroxycinnamic acid derivatives.
AB  - As a powerful natural antioxidant, lipoic acid exerts significant antioxidant
      activities in vivo and in vitro by deactivation of reactive oxygen and nitrogen
      species. In this study we present a novel synergistic interaction of lipoic acid
      with other endogenous or exogenous antioxidants. Antioxidants vitamins C and E
      analogue (Trolox C) and hydroxycinnamic acid derivatives were found to recycle
      lipoic acid by donating electrons to lipoic acid radical cations, thereby
      increasing the antioxidant capacity of lipoic acid in vivo and in vitro. The rate
      constant of the electron transfer is in the order 10(9)dm(3)mol(-1)s(-1), close
      to the diffusion-controlled limit, and transfer quantum yield is above 95%.

PMID- 12234494
TI  - Roles of Asp54 and Asp213 in Ca2+ utilization by soluble human CD39/ecto
      nucleotidase.
AB  - Soluble human CD39 (solCD39) rapidly metabolizes nucleotides, especially ADP
      released from activated platelets, thereby inhibiting further platelet activation
      and recruitment. Using alanine substitution mutagenesis, we established a
      functional role for aspartates D54 and D213 in solCD39. Kinetic analyses of D54A
      and D213A indicated decreased K(m)s of the mutants, compared to wild type, for
      the cofactor calcium and for the substrates ADP and ATP. These decreases in
      calcium and nucleotide affinity of the mutants were accompanied by increases in
      their rate of catalysis. The decreased affinity of the mutants for calcium was
      responsible for their diminished ability to reverse platelet aggregation in
      plasma anticoagulated with citrate, a known calcium chelator. Their ADPase
      activity in the presence of citrated plasma was also decreased, although this
      could be overcome with excess calcium. Thus, aspartates 54 and 213 are involved
      in calcium utilization and potentially involved in cation coordination with
      substrate in the catalytic pocket of solCD39.

PMID- 12234495
TI  - Yeast mitochondrial oxodicarboxylate transporters are important for growth on
      oleic acid.
AB  - The yeast genes ODC1 and ODC2 encode members of the Saccharomyces cerevisiae
      family of mitochondrial transport proteins that transport oxodicarboxylates. In
      these studies, the ODC1 gene was identified as able, in low-copy, to rescue a
      yeast strain that is unable to grow on oleic acid but can grow on other
      nonfermentable carbon sources. ODC2 was shown to be a high-copy suppressor of
      this mutant. Odc1delta odc2delta double mutants are unable to grow on oleic acid
      at 36 degrees C. ODC1 mRNA and protein expression is elevated in oleic acid
      medium as compared to glucose or glycerol. The ODC1 promoter contains sequences
      required for the oleic acid response. However, regulation of ODC1 does not
      require the transcription factors Oaf1p and Pip2p, known to mediate oleic acid
      induction of other genes. These studies provide the first link between these
      mitochondrial transporters and peroxisomal beta-oxidation.

PMID- 12234496
TI  - Cloning, expression, and characterization of a soluble calcium-activated
      nucleotidase, a human enzyme belonging to a new family of extracellular
      nucleotidases.
AB  - The salivary apyrases of blood-feeding arthropods are nucleotide-hydrolyzing
      enzymes implicated in the inhibition of host platelet aggregation through the
      hydrolysis of extracellular adenosine diphosphate. A human cDNA homologous to the
      apyrase cDNA of the blood-feeding bed bug was identified, revealing an open
      reading frame encoding a 371-amino acid protein. A cleavable signal peptide
      generates a secreted protein of 333 residues with a predicted core molecular mass
      of 37,193 Da. Expression in COS-1 cells produced a secreted apyrase in the cell
      media. The ADPase and ATPase activities were dependent upon calcium, with a pH
      optimum between pH 6.2 and 7.2. Interestingly, the preferred substrate was not
      ADP, as might be expected for an enzyme modulating platelet aggregation, but
      rather UDP, followed by GDP, UTP, GTP, ADP, and ATP. The nucleotidase did not
      hydrolyze nucleoside monophosphates. Size-exclusion chromatography and Western
      blot analysis revealed a molecular mass of approximately 34-37 kDa. Treatment of
      the enzyme with peptide N-glycosidase F indicated that the protein is
      glycosylated. Northern analysis identified the transcript in a range of human
      tissues, including testis, placenta, prostate, and lung. No traditional apyrase
      conserved regions or nucleotide-binding domains were identified in this human
      enzyme, indicating membership in a new family of extracellular nucleotidases.

PMID- 12234497
TI  - Electron acceptor specificity of ferredoxin (flavodoxin):NADP+ oxidoreductase
      from Escherichia coli.
AB  - Reduced flavodoxin I (Fld1) is required in Escherichia coli for reductive radical
      generation in AdoMet-dependent radical enzymes and reductive activation of
      cobalamin-dependent methionine synthase. Ferredoxin (Fd) and flavodoxin II (Fld2)
      are also present, although their precise roles have not been ascertained.
      Ferredoxin (flavodoxin):NADP+ oxidoreductase (FNR) was discovered in E. coli as
      an NADPH-dependent reductant of Fld1 that facilitated generation of active
      methionine synthase in vitro; FNR and Fld1 will also supply electrons for the
      reductive cleavage of AdoMet essential for generating protein or substrate
      radicals in pyruvate formate-lyase, class III ribonucleotide reductase, biotin
      synthase, and, potentially, lipoyl synthase. As part of ongoing efforts to
      understand the various redox pathways that will support AdoMet-dependent radical
      enzymes in E. coli, we have examined the relative specificity of E. coli FNR for
      Fd, Fld1, and Fld2. While FNR will reduce all three proteins, Fd is the
      kinetically and thermodynamically preferred partner. Fd binds to FNR with high
      affinity (K(d)<or=0.5 microM) and is reduced under single-turnover conditions
      with k(obs)=2.3s(-1) and under steady state conditions with k(cat)=0.15s(-1).
      Fld1 and Fld2 behave similarly with respect to FNR, with affinities approximately
      4- to 7-fold weaker and reduction rates that are 10- to 100-fold slower than
      those for Fd. Surprisingly we find that Fld1 and Fld2 can obtain electrons from
      reduced Fd at rates that are comparable to those obtained with reduced FNR. Thus
      we propose that the primary electron acceptor for E. coli FNR is Fd, while Fld1
      can obtain electrons slowly either from FNR or via Fd as a mediator.

PMID- 12234498
TI  - Chemo-enzymatic synthesis of the glycosylated alpha-mating factor of
      Saccharomyces cerevisiae and analysis of its biological activity.
AB  - The effect of glycosylation on a bioactive peptide was studied using yeast
      Saccharomyces cerevisiae alpha-mating factor, which is composed of 13 amino
      acids. In this study, we prepared glycosylated alpha-mating factor by chemo
      enzymatic synthesis. At first, N-acetylglucosaminyl alpha-mating factor (Trp-His
      Trp-Leu-Gln(GlcNAc)-Leu-Lys-Pro-Gly-Gln-Pro-Met-Tyr) was chemically synthesized
      by the solid-phase method. Then, using the transglycosylation activity of Mucor
      hiemalis endo-beta-N-acetylglucosaminidase, we synthesized glycosylated alpha
      mating factor with a glutamine-linked sialo complex type oligosaccharide. The
      biological activity of alpha-mating factor derivatives was examined by means of a
      growth arrest assay using secreted-protease-defective a cells of S. cerevisiae.
      The results showed that the bioactivity of glycosylated alpha-mating factor was
      lower than that of native alpha-mating factor. However, when sialic acid was
      removed from the complex type sugar chain of glycosylated alpha-mating factor,
      its bioactivity was recovered. Glycosylated alpha-mating factor exhibited higher
      resistance against proteolysis than native alpha-mating factor. It was found that
      the bioactivity of N-acetylglucosaminyl alpha-mating factor was higher than that
      of alpha-mating factor. Circular dichroism studies indicated that a slight change
      in the structure of alpha-mating factor may influence its activity.

PMID- 12234499
TI  - Specificity of chloroplast-localized peptide deformylases as determined with
      peptide analogs of chloroplast-translated proteins.
AB  - Peptide deformylase (DEF; EC 3.5.1.88) removes the N-formyl group from nascent
      polypeptides. Two nuclear-encoded DEFs in Arabidopsis thaliana (At) are localized
      to chloroplasts, and thus, the N-termini of chloroplast-translated proteins may
      be a consequence of AtDEFs' substrate specificity. Using peptide analogs of
      select chloroplast-translated proteins, AtDEF1 activity was as much as 100-fold
      lower than AtDEF2 activity and showed little variance with peptide sequence.
      However, AtDEF2 activity was significantly influenced by peptide sequence, with
      the most efficiently processed substrate mimicking the N-terminus of the nascent
      D1 polypeptide, a core protein of photosystem II. Though AtDEF2's specificity was
      predictive of N-formyl retention for some chloroplast proteins, exceptions
      suggests that additional factors in vivo aid in determining the retention of an N
      formyl group.

PMID- 12234500
TI  - Role of adrenoceptor subtypes in memory consolidation.
AB  - Noradrenaline release in areas within the forebrain occurs following activation
      of noradrenergic cells in the locus coeruleus (LoC). Release of noradrenaline by
      attentional/arousal/vigilance factors appears to be essential for learning and is
      responsible for the consolidation of memory. Noradrenaline can activate any of
      nine different adrenoceptor (AR) subtypes in the brain and selectivity of action
      may be achieved by the spatial location and relative density of the AR subtypes,
      by different affinities of the different subtypes and by temporal selectivity in
      terms of when the different ARs are activated in the memory formation process.
      This review examines the use of selective agonists and antagonists to determine
      the roles of the AR subtypes in the one-trial discriminated avoidance learning
      paradigm in the chick. A model is developed that integrates noradrenergic
      activity in basal ganglia (lobus parolfactorius (LPO)) and association cortex
      (intermediate medial hyperstriatum ventrale (IMHV)) leading to the consolidation
      of memory 30 min after training. There is evidence that beta(2)- and beta(3)-ARs
      are important in the association area but require input from alpha(2)-AR
      stimulated activity in the basal ganglia for consolidation. On the other hand,
      alpha(1)-AR activation in the IMHV is inhibitory and prevents consolidation.
      While there is no role for beta(1)-ARs in memory consolidation, they play a role
      in short-term memory (STM). The use of the precocial chick has clear advantages
      in having a temporally discrete learning task which allows for discrimination
      memory and whose development can be followed at discrete intervals after
      learning. These studies reveal clear roles for AR subtypes in the formation and
      consolidation of memory in the chick, which have allowed the development of a
      model that can now be tested in mammalian systems.

PMID- 12234501
TI  - MR microscopy and high resolution small animal MRI: applications in neuroscience
      research.
AB  - The application of magnetic resonance (MR) imaging in the study of human disease
      using small animals has steadily evolved over the past two decades and strongly
      established the fields of "small animal MR imaging" and "MR microscopy." An
      increasing number of neuroscience related investigations now implement MR
      microscopy in their experiments. Research areas of growth pertaining to MR
      microscopy studies are focused on (1). phenotyping of genetically engineered mice
      models of human neurological diseases and (2). rodent brain atlases. MR
      microscopy can be performed in vitro on tissue specimens, ex vivo on brain slice
      preparations and in vivo (typically on rodents). Like most new imaging
      technologies, MR microscopy is technologically demanding and requires broad
      expertise. Uniform guidelines or "standards" of a given MR microscopy experiment
      are non-existent. The main focus therefore of this review will be on biological
      applications of MR microscopy and the experimental requirements. We also take a
      critical look at the biological information that small animal (rodent) MR imaging
      has provided in neuroscience research.

PMID- 12234502
TI  - EAU guidelines on penile cancer.

PMID- 12234503
TI  - A randomised comparison of bicalutamide ('Casodex') 150 mg versus placebo as
      immediate therapy either alone or as adjuvant to standard care for early non
      metastatic prostate cancer. First report from the Scandinavian Prostatic Cancer
      Group Study No. 6.
AB  - OBJECTIVES: To assess the efficacy and tolerability of bicalutamide 150 mg
      ('Casodex'(1)) as immediate therapy, either alone or as adjuvant to treatment of
      curative intent, in patients with early (T1b-T4, any N, M0) prostate cancer.
      METHODS: This randomised, double-blind study was conducted in the Nordic
      countries as part of the 'Casodex' Early Prostate Cancer programme. Patients
      received bicalutamide 150 mg (n=607) or placebo (n=611) in addition to standard
      care. RESULTS: More than 80% of patients had not received therapy of primary
      curative intent. Median follow-up in both groups was 3 years. Median exposure to
      study treatment in the bicalutamide and standard care alone groups was 2.5 and
      2.3 years, respectively. Bicalutamide reduced the risk of objective disease
      progression by 57% compared with standard care alone (HR 0.43; 95% CI 0.34, 0.55;
      p<<0.0001). Survival data were immature (11.4% deaths) with no difference between
      the two treatment groups. CONCLUSIONS: Bicalutamide 150 mg as immediate therapy,
      either alone or as adjuvant to treatment of curative intent, significantly
      reduces the risk of disease progression in patients with early prostate cancer.
      The trial is ongoing to assess whether the reduction in risk of objective
      progression translates into an overall survival benefit.

PMID- 12234504
TI  - Long-term follow-up of radical retropubic prostatectomy for prostate cancer.
AB  - OBJECTIVES: The ultimate outcome of patients after radical prostatectomy is often
      predicted from statistical projections of short-term follow-up. Only actual long
      term follow-up can demonstrate true outcome. METHODS: One hundred thirty-one
      patients underwent retropubic prostatectomy for clinically organ confined
      prostate cancer and have been followed for a minimum of 22.5 years.
      Preoperatively, all but 12 had clinically palpable cancer. RESULTS: Overall
      survival in these patients was similar to an age-matched population, with 65%
      alive at 15 years, and 23% alive at 25 years. Thirty-seven percent of the
      patients recurred and 24% of all the patients died of prostate cancer. For
      patients with pathologically organ confined disease, 27% recurred, while those
      with extension outside the gland or positive nodes had an 83% recurrence rate.
      Although, the median time to recurrence was 7 years, recurrences occurred at a
      steady-state throughout the length of follow-up. Patients with higher grade
      tumors, even if organ confined, were significantly more likely to recur.
      CONCLUSIONS: In a cohort of patients treated with radical prostatectomy for
      predominantly palpable disease, long-term follow-up (79% deceased) reveals that
      37% will recur and 24% will die of prostate cancer. Almost half the recurrences
      occurred after 10 years, indicating that reports with shorter follow-up will
      underestimate the recurrence rate.

PMID- 12234505
TI  - Lack of effect of intrarectal lidocaine for pain control during transrectal
      prostate biopsy: a randomized prospective study.
AB  - INTRODUCTION AND OBJECTIVES: Transrectal ultrasound guided biopsy is an essential
      part in the diagnosis of prostate cancer. Although this procedure is well
      tolerated by most patients, sometimes it can result in some uneasiness. In this
      randomised double-blind placebo controlled study, we evaluated the effectiveness
      of intrarectal lidocaine during TRUS guided biopsy. MATERIALS AND METHODS: 100
      consecutive eligible patients who had elevated total prostate specific antigen
      (tPSA) and/or abnormal digital rectal examination (DRE) were included into this
      study. Patients were randomised into two groups. Group I received 20 cc of 2%
      intrarectal lidocaine 20 minutes before transrectal ultrasound guided biopsy and
      Group II received same amount of serum physiologic. Pain was assessed using a 10
      point modified visual analog scale. RESULTS: Mean patient age was 65.5+/-2.5 and
      64.5+/-11.5 years, mean tPSA was 12.3+/-3.6 and 11.3+/-1.7 ng/ml, mean biopsy
      duration was 6.8+/-2.5 and 6.6+/-2.2 minutes, mean pain score during transrectal
      ultrasound guided biopsy was 4.8+/-2.2 and 4.4+/-2.1 in Groups I and II,
      respectively. No statistically significant difference was observed with respect
      to age, tPSA, mean biopsy duration and pain score between these groups. There was
      only one patient who could not tolerate the procedure at all, and he was
      paradoxically in the lidocaine group. CONCLUSION: The use of intrarectal
      lidocaine is not superior to placebo during transrectal prostate biopsy for pain
      control.

PMID- 12234506
TI  - Ultrasound-guided fine needle cytology of retroperitoneal masses in patients with
      malignant germ cell tumours: diagnosis and therapeutic impact.
AB  - PURPOSE: There are few reports on the use of fine needle cytology (FNC) for the
      detection of retroperitoneal lymph node metastases from malignant germ cell
      tumours (MGCT). In order to determine efficiency of the procedure and its impact
      on therapeutic approaches, this study reviews experience with ultrasound-guided
      transabdominal FNC in patients with MGCT. PATIENTS AND METHODS: Twenty-four
      patients with known malignant germ cell tumour and four patients without previous
      histology, presented with retroperitoneal masses. They underwent ultrasound
      guided fine needle cytology (aspirations were done twice in two patients).
      Clinical data were retrieved from the medical records and all cytological
      specimens were reviewed. In metastatic cases, the cytologic findings were
      correlated with the histology of the primary tumour. RESULTS: Twenty-one of 30
      specimens (70%) were diagnosed as malignant, 6 (20%) were benign, and 3 (10%)
      were unsatisfactory for the cytologic diagnosis. Five of the 21 malignant lesions
      were < or =10mm. FNC yielded the correct diagnosis in all four cases of
      extragonadal malignant germ cell tumours. In four other patients, FNC solved
      significant staging problems at the diagnosis. In 7 of 11 patients with the
      suspicion of retroperitoneal recurrence and normal serum tumour markers during
      follow-up, FNC confirmed the malignant morphology of the lesions. CONCLUSIONS: In
      experienced hands, ultrasound-guided FNC can be a valuable method for the
      morphological diagnosis of retroperitoneal manifestations from MGCT. FNC should
      be added in follow-up and staging procedures (radiological imaging and serum
      tumour markers) in selected patients in whom the histological verification of
      such lesions is critical for the patient's management.

PMID- 12234507
TI  - Gonadal function and fertility in patients with bilateral testicular germ cell
      malignancy.
AB  - OBJECTIVE: To evaluate gonadal function and fertility in patients with bilateral
      testicular cancer (TC). METHODS: In 1999, 63 patients with bilateral invasive TC
      or carcinoma in situ (CIS) in the contralateral testis completed a mailed
      questionnaire evaluating their fatherhood (Cases). Their gonadal function had
      also been assessed after the first orchiectomy for TC before further treatment.
      The results were compared with those from 174 patients with unilateral TC
      (Controls). RESULTS: In Cases the post-orchiectomy serum levels of FSH and LH
      were above those of the Controls (p<0.001). Serum testosterone was similar,
      whereas sperm concentrations were lower in Cases (p<0.001). In Cases with
      metachronous invasive TC the level of serum FSH was associated with the interval
      between the two diagnoses. After the first orchiectomy, 10 of 25 Cases (40%)
      initiated a pregnancy, in 4 Cases by assisted fertilization. In the Control group
      74% of the patients who attempted fatherhood succeeded (p=0.002). CONCLUSIONS:
      After unilateral orchiectomy for TC elevated serum FSH and/or oligospermia
      represent a high-risk factor of metachronous bilateral TC or synchronous CIS. At
      least one-third of these patients attempting fatherhood are successful after the
      first orchiectomy. Assisted fertilization is often necessary and the overall
      paternity rate is below that of patients with unilateral TC.

PMID- 12234508
TI  - A new biopsy technique to investigate Peyronie's disease associated histologic
      alterations: results with two different forms of therapy.
AB  - OBJECTIVES: Peyronie's disease is the most frequent cause of penile curvature and
      occurs particularly in middle-age patients. The best technique for penile biopsy,
      in the evaluation of albuginea and cavernous tissue, has not been delineated yet.
      We present a new technique of penile biopsy, useful in the study of Peyronie's
      plaque, fibrosis and erectile dysfunction or any other pathological condition of
      the penis requiring a biopsy. METHODS: A treatment group (A) of 380 patients
      underwent Extra Shock Waves Treatment (ESWT) three times a week for 20 minutes,
      followed by a complete cycle of 12 injections of verapamil (10mg), every two
      weeks for six months. A control group (B) of 92 patients underwent verapamil
      injections alone. Three months after the end of the treatment, each patient
      underwent penile biopsy performed with Acu-Punch (Acuderm Inc.), a biopsy-punch
      armed with a well-sharpened rotating cylindrical blade, first used by
      dermatologists for cutaneous lesions. RESULTS: A reduction of the plaque volume
      was found in 260/380 patients (68.4%) of group A and in 28/92 (30.4%) of group B;
      painful erection weaned off in 312/340 patients of group A (91.7%) and in 36/82
      patients (43.9%) of group B. In all 472 patients an excellent specimen was
      obtained and both the tunica albuginea and the cavernous tissue were easily
      identified. In the 260 cases, in which the Extra Shock Waves Treatment was
      successful, scanning and transmission electron microscopy demonstrated a
      reduction in packing and clumping of the collagen fibers. CONCLUSIONS: This new
      technique of penile biopsy with Acu-Punch can replace surgical biopsies when a
      surgical operation is not indicated. Such a low-invasive technique could be
      performed in all cases of Peyronie's disease and allows a more extensive use of
      microscopic analysis in the study of Peyronie's disease.

PMID- 12234509
TI  - A new technique for augmentation phalloplasty: albugineal surgery with bilateral
      saphenous grafts--three years of experience.
AB  - OBJECTIVES: Penile augmentation surgery is a highly controversial issue due to
      the low level of standardisation of surgical techniques. The aim of the study is
      to illustrate a new technique to solve the problem of enlarging the penis by
      means of additive surgery on the albuginea of the corpora cavernosa, guaranteeing
      a real increase in size of the erect penis. METHODS: Between 1995 and 1997, 39
      patients who requested an increase in the diameter of their penises underwent
      augmentation phalloplasty with bilateral saphena grafts. The patients considered
      eligible for surgery were patients with either hypoplasia of the penis or
      functional penile dysmorphophobia. All the patients included in our study
      presented normal erection at screening. The average penis diameter in a flaccid
      state and during erection was found to be 2.1cm (1.6-2.7 cm) and 2.9 cm (2.2-3.7
      cm), respectively. Before surgery the patients were informed of the experimental
      nature of the surgical procedure. The increase in volume of the corpora cavernosa
      was achieved by applying saphena grafts to longitudinal openings made bilaterally
      in the albuginea along the whole length of the penis. RESULTS: No major
      complications and specifically no losses of sensitivity of the penis or erection
      deficiencies occurred during the post-operative follow-up period. All the
      patients resumed their sexual activity in 4 months. A measurement of the penile
      dimensions was carried out 9 months after surgery. No clinical meaningful
      increases in the diameter of the flaccid penis were documented. The average penis
      diameter during erection was found to be 4.2 cm (3.4-4.9) with post-surgery
      increases in diameter varying from 1.1 to 2.1cm (p<0.01). CONCLUSIONS: The penile
      enlargement phalloplasty technique with albuginea surgery suggested by the
      authors definitely is indicated for increasing the volume of the corpora
      cavernosa during erection. Albuginea surgery with saphena grafts has been found
      to be free from aesthetic and functional complications with excellent patient
      satisfaction.

PMID- 12234510
TI  - Study of the association between ischemic heart disease and use of alpha-blockers
      and finasteride indicated for the treatment of benign prostatic hyperplasia.
AB  - OBJECTIVE: Given the high possibility of co-occurrence of benign prostatic
      hyperplasia (BPH) and cardiovascular disease, we evaluated whether patients using
      BPH drugs are at an increased risk of acute hospital admission for ischemic heart
      disease (IHD). METHODS: A nested case control study within a cohort of 4414 men
      (aged > or =30 years) who had a history of using BPH products between 1992 and
      1998 was conducted. Cases were defined as men with a first record of an acute
      hospital admission for IHD during the study period; three controls were matched
      to each case on year of birth, pharmacy and calendar time (index date). RESULTS:
      The study population comprised 220 cases and 515 controls. Current use of alpha
      blockers (adjusted odds ratio 1.0, 95% confidence interval: 0.5-2.2) or
      finasteride (adjusted odds ratio 0.3, 95% CI: 0.1-1.4) was not associated with
      hospital admission for IHD. Furthermore, current use of BPH drugs was not
      associated with IHD in patient subgroups (age, history of cardiovascular disease,
      diabetes), nor with duration of use prior to hospitalization. CONCLUSION:
      Although the power of the study was low, we found no evidence for an association
      between current use of BPH drugs and hospital admission for IHD. Therefore, our
      study seems to confirm the good cardiovascular safety profile of modern BPH
      drugs.

PMID- 12234511
TI  - The use of biodegradable PGA stents to judge the risk of post-TURP incontinence
      in patients with combined bladder outlet obstruction and overactive bladder.
AB  - OBJECTIVE: For patients with the combination of severe bladder outlet obstruction
      (BOO) and severe overactive bladder (OB), no straightforward and safe treatment
      exists due to the risk of urge incontinence after TURP. In this study we have
      used a biodegradable polyglycolic stent to simulate the status after TURP and
      register the risk for urge incontinence. METHODS: A total of 37 patients with
      severe OB, combined with moderate to severe BOO, were asked if they wanted to
      participate. Under cystoscopic vision a polyglycolic biodegradable stent was
      inserted in the prostatic urethra. RESULTS: Twenty-five of the patients noticed
      no or only minor leakage and 19 of these have been subjected to TURP with good
      results. Three patients are on the waiting-list for TURP. Twelve of 37 patients
      were found to have major leakage after stent insertion. During the stent period,
      we noted five cases of complications, due to UTI, stent crash and irritation. All
      of these patients recovered within three weeks. CONCLUSIONS: A biodegradable PGA
      stent seems to be a new and unique tool to test the risk for post-TURP
      incontinence in patients with combined BOO and severe OB.

PMID- 12234512
TI  - Laparoscopic dismembered pyeloplasty--the method of choice in the presence of an
      enlarged renal pelvis and crossing vessels.
AB  - OBJECTIVE: Herein we report our experience of 49 consecutive pyeloplasties that
      were all laparoscopically performed with an intracorporeally sutured anastomosis.
      We describe the operative technique, complications and outcomes during a follow
      up period of 1-53 months (mean 23.2 months). PATIENTS AND METHODS: Forty-nine
      patients (28 women and 21 men) with a mean age of 34 years (range 6-65 years)
      underwent a laparoscopic dismembered pyeloplasty because of primary ureteropelvic
      junction (UPJ) obstruction with hydronephrosis in each case. The preoperative
      evaluation included an evaluation for pain, an excretory urography (IVP), renal
      scan and sometimes CT angiography to evaluate for crossing vessels. Follow-up
      studies included an IVP, renal scan and renal ultrasound 4 weeks postoperatively
      and every 3 months thereafter. Success was considered as improvement of the pain
      score and IVP (less hydronephrosis, visible UPJ and/or normalization of drainage)
      or absence of an obstructive pattern during the washout phase of a renal scan.
      RESULTS: There was no conversion to open surgery. The mean operative time was 165
      min (range 90-240 min). Blood loss was negligible. Crossing vessels were noted in
      57.1% of the patients (28/49). Postoperative hospital stay was 3.7 days (range 3
      6 days). One patient had a leakage of the anastomosis on postoperative day 1 and
      needed to undergo laparoscopic repair. The mean follow-up is 23.2 months (range 1
      53 months). There was one single late failure. This patient later underwent an
      open revision of the laparoscopic pyeloplasty. In all other patients (48/49), the
      obstruction was resolved or significantly improved. The long-term success rate is
      97.7%. CONCLUSIONS: The results of dismembered laparoscopic pyeloplasties compare
      favorably with those achieved by open pyeloplasties with less perioperative
      morbidity and discomfort. We do believe that laparoscopic dismembered pyeloplasty
      with an intracorporeal anastomosis is the method of choice in the treatment of
      the UPJ obstruction in the presence of an enlarged renal pelvis and crossing
      vessels.

PMID- 12234513
TI  - Externally coated ureteral metallic stents: an unfavorable clinical experience.
AB  - OBJECTIVE: The purpose of the present study was to evaluate the use of externally
      coated stents in patients with malignant ureteral obstruction. MATERIALS AND
      METHODS: We have prospectively evaluated 16 patients, 10 men and 6 women, with
      malignant ureteral obstruction treated successfully by placement of Passager
      metal stents (Boston Scientific, Natick, MA, USA) bypassing the stricture. Mean
      patient age was 65.6 years (range 62-78 years). Ureteral patency was confirmed 24
      and 48 hours by injection of contrast material through the nephrostomy tube, and
      after patency confirmation the nephrostomy catheter was removed. RESULTS: All
      stents were positioned successfully, and the postoperative course was uneventful.
      In 13 cases (81.2%) the prostheses finally migrated into the bladder hindering
      overall ureteral patency (mean time of migration: 1.5 months). Patency was
      achieved in the remaining ureters (n=3), during the follow-up period (mean: 8
      months, range 6-16 months), without any need for further intervention.
      CONCLUSION: The inappropriate anchorage and the increased ureteral peristalsis
      are the main causes of migration towards the bladder, thus, minimizing the
      usefulness of this stent for the treatment of ureteral strictures.

PMID- 12234514
TI  - Modulation of viscero-somatic H-reflex during bladder filling: a possible tool in
      the differential diagnosis of neurogenic voiding dysfunctions.
AB  - OBJECTIVE: Despite evidence that the activation of visceral afferents modulates
      spinal motoneurone activity in humans, the circuits responsible for this
      modulation remain unclear. The aim of the present study was to assess the effect
      of urinary bladder filling on the excitability of somatic spinal motoneurones in
      patients affected by overactive bladder secondary to neurogenic and non
      neurogenic causes in both patients with bladder underactivity and normal subjects
      by means of a urodynamic evaluation. METHODS: In order to evaluate the influence
      of bladder filling on somatic reflexes, we studied the H-reflex evoked by
      electrical stimuli applied to the tibial nerve at the popliteal fossa and
      recorded from the soleus muscle. The H-reflex was tested in the following
      conditions: (1). empty bladder; (2). medium bladder filling; (3). maximum bladder
      filling; (4). five minutes after bladder emptying. The H-reflex amplitude at
      empty bladder was considered as the control value. RESULTS: In healthy subjects,
      we observed a progressive reduction in the H-reflex amplitude during bladder
      filling. In spinal cord-injured patients affected by a neurogenic overactive
      bladder, bladder filling failed to inhibit the H-reflex amplitude; a decrease in
      the H-reflex amplitude similar to that displayed by normal subjects was observed
      in patients with a non-neurogenic overactive bladder. By contrast, H-reflex
      behavior was unmodified in neurogenic underactive bladder patients and was
      similar to normal subjects in psychogenic underactive patients. CONCLUSIONS: As
      behavior of the H-reflex varies during bladder filling in neurogenic and non
      neurogenic overactive bladder patients as well as in neurogenic and non
      neurogenic underactive bladder patients, H-reflex modulation may be considered a
      useful tool in the differential diagnosis of voiding dysfunctions.

PMID- 12234515
TI  - The effect of different diets on urine composition and the risk of calcium
      oxalate crystallisation in healthy subjects.
AB  - OBJECTIVE: The aim of the study was to determine the impact of defined diet
      modifications on urine composition and the risk of calcium oxalate
      crystallisation. METHODS: Ten healthy male volunteers consumed a self-selected
      diet (SD) for 14 days, and three different standard diets for a period of 5 days
      each. Whereas the western-type diet (WD) is representative of the usual dietary
      habits, the normal mixed diet (ND) and the ovo-lacto-vegetarian diet (VD) were
      calculated according to the requirements. RESULTS: The risk of calcium oxalate
      crystallisation, calculated as relative supersaturation (EQUIL2) from urine
      composition, was highest during ingestion of diets SD and WD. The intake of diet
      ND resulted in a significant decrease in relative supersaturation with calcium
      oxalate by 58% (p<0.05) compared with diet WD, due to a significant decline in
      urinary calcium and uric acid excretion and a significant increase in urinary
      volume, pH-value and citrate excretion. In spite of an increase in urinary pH,
      citrate and magnesium excretion and a decline in calcium excretion, no further
      significant decrease in the risk of calcium oxalate crystallisation was observed
      on diet VD, due to a significant increase in urinary oxalate by 30% (p<0.05) on
      average. CONCLUSIONS: The change of usual dietary habits for a normal mixed diet
      significantly reduces the risk of calcium oxalate crystallisation. With a
      vegetarian diet a similar decline in urinary supersaturation with calcium oxalate
      can be achieved compared to a normal mixed diet. Since urinary oxalate excretion
      increased significantly, a vegetarian diet without adequate intake of calcium may
      not be recommended to patients with mild hyperoxaluria.

PMID- 12234516
TI  - Blunt renal trauma in children: 26 years clinical experience in an alpine region.
AB  - OBJECTIVES: From 1975 to 2001, 254 children aged younger than 17 were transferred
      to our department for renal trauma. We performed a retrospective study to assess
      causality and kind of the trauma, diagnostic procedures and therapeutic
      consequences, respectively. METHODS: The 254 children at a mean age of 10.56
      years (+/-3.8) ranging from 2 to 17 years were treated for kidney trauma. Among
      these, 166 presented with a grade I trauma according to the kidney injury scale
      of the American Association for the Surgery of Trauma without any other
      accompanying injuries and 88 had a grade II-V lesion, respectively. Diagnostic
      evaluation included various standard lab tests such as urinalysis and routine
      blood parameters, ultrasound, IVP and/or CT. RESULTS: Most of the traumatic
      injuries resulted from skiing accidents. However, 18 children had a severe
      polytrauma with laceration of other vital organs. Most of the renal injuries
      could be treated conservatively. Surgical treatment options included immediate
      exploration, reconstruction, partial resection, or even nephrectomy. No child
      died. CONCLUSIONS: Due to leisure time activities in our region, skiing accidents
      often result in isolated laceration of the kidney. About one third presented with
      a severe kidney trauma, and approximately 20% of all affected children required
      surgical therapy. However, most of the injured kidneys could be preserved and
      only four nephrectomies had to be performed.

PMID- 12234517
TI  - A candidate gene approach within the susceptibility region PCaP on 1q42.2-43
      excludes deleterious mutations of the PCTA-1 gene to be responsible for
      hereditary prostate cancer.
AB  - OBJECTIVE: The Prostate Carcinoma Tumor Antigen-1 (PCTA-1) is located at the
      prostate cancer susceptibility locus on chromosome 1q42.2-43 (PCaP). In this
      candidate gene approach, we searched for deleterious mutations within the PCTA-1
      gene and its promoter. MATERIALS AND METHODS: Seventy-seven familial prostate
      cancer cases from 36 German and French pedigrees were screened for germline
      mutations in the PCTA-1 gene using enzymatic mutation detection (EMD). Putative
      missense mutations were genotyped by RPLP and ddNTP primer extension assays in 88
      controls to assess allele frequencies and haplotypes. RESULTS: Several sequence
      variants were found but none of the findings indicated a deleterious mutation.
      Three affected brothers showed an intronic variation, which may interfere with
      correct splicing. Four non-conservative SNPs were characterized, coding for the
      amino acid alterations Y19F, C36R, V56M and S184R. All exchanges were found in
      controls with common allelic frequencies of at least 28%. Haplotype definition
      including six SNPs within the PCTA-1 gene revealed a complete linkage
      disequilibrium. Low haplotype diversity leads to a predominance of only two
      peptide variants of the PCTA-1 protein, coded by 95% of all chromosomes.
      CONCLUSIONS: PCTA-1 is not a classical high risk gene with deleterious mutations
      predisposing to hereditary prostate cancer. Its contribution to prostate cancer
      susceptibility as a low risk factor in sporadic disease has to be assessed in
      larger samples by association studies.

PMID- 12234520
TI  - The FLEXGene repository: exploiting the fruits of the genome projects by creating
      a needed resource to face the challenges of the post-genomic era.
AB  - Thanks to the results of the multiple completed and ongoing genome sequencing
      projects and to the newly available recombination-based cloning techniques, it is
      now possible to build gene repositories with no precedent in their composition,
      formatting, and potential. This new type of gene repository is necessary to
      address the challenges imposed by the post-genomic era, i.e., experimentation on
      a genome-wide scale. We are building the FLEXGene (Full Length EXpression-ready)
      repository. This unique resource will contain clones representing the complete
      ORFeome of different organisms, including Homo sapiens as well as several
      pathogens and model organisms. It will consist of a comprehensive, characterized
      (sequence-verified), and arrayed gene repository. This resource will allow full
      exploitation of the genomic information by enabling genome-wide scale
      experimentation at the level of functional/phenotypic assays as well as at the
      level of protein expression, purification, and analysis. Here we describe the
      rationale and construction of this resource and focus on the data obtained from
      the Saccharomyces cerevisiae project.

PMID- 12234521
TI  - Genetic immunization: what's in a name?
AB  - The concept and demonstration of genetic immunization (GI) was first introduced
      in 1992. At the time it appeared to be a revolutionary new approach in
      vaccinology. Since then, genetic immunization has been applied with much success
      in a wide variety of model and natural systems. It has also been used in several
      human clinical trials. Currently there is a general impression that genetic
      immunization has limitations inhibiting its broad use. The technique is thought
      to be poor at antibody production and more importantly not to work well in
      primates and humans (simian barrier). However, recent reports addressing these
      issues (poor antibody production and the simian barrier) showed improvements of
      GI to produce protective immune responses in humans. We propose that the apparent
      limitations of gene vaccines may arise from not using the technologies' potential
      to manipulate the immune system. This dearth of imaginative use is manifested in
      the tendency by some to term the technique DNA immunization. The apparent
      limitations of DNA vaccines may not be limitations for gene vaccines.

PMID- 12234522
TI  - The global emergence/resurgence of arboviral diseases as public health problems.
AB  - During the past 20 years there has been a dramatic resurgence or emergence of
      epidemic arboviral diseases affecting both humans and domestic animals. These
      epidemics have been caused primarily by viruses thought to be under control such
      as dengue, Japanese encephalitis, yellow fever, and Venezuelan equine
      encephalitis, or viruses that have expanded their geographic distribution such as
      West Nile and Rift Valley fever. Several of these viruses are presented as case
      studies to illustrate the changing epidemiology. The factors responsible for the
      dramatic resurgence of arboviral diseases in the waning years of the 20th century
      are discussed, as is the need for rebuilding the public health infrastructure to
      deal with epidemic vector-borne diseases in the 21st century.

PMID- 12234523
TI  - Infectious diseases in Mexico. A survey from 1995-2000.
AB  - Data obtained at a central laboratory for emerging, re-emerging, and other
      infectious diseases in Mexico from 1995-2000 are presented. An outstanding
      increase of DEN-3 circulation was identified. Aedes aegypti, the dengue vector,
      is widely distributed. Leptospirosis has become the most important differential
      diagnosis for dengue. Identification of rabies virus variants allowed cataloging
      of new transmitters of rabies. Rotavirus showed a clear seasonal distribution,
      while different proportions of pathogenic classes of Escherichia coli under
      endemic and outbreak conditions were seen. Serotypes of several bacteria are
      reported as well as the sources of isolation and frequency of Shigella,
      Salmonella, and Vibrio cholerae. Rise and disappearance of cholera could be
      followed along the past decade. Influenza strains were identified, as were
      several pathogens causing sexually transmitted infections. Laboratory support was
      important for surveillance after Hurricane Mitch. Multidrug-resistant strains of
      Mycobacterium tuberculosis are emerging and primary resistance is very high. It
      is now mandatory to search for antibodies to Trypanosoma cruzi in blood banks.
      Triatoma barberi, a peridomestic bug, is the main vector of Chagas disease.
      Localized cutaneous leishmaniosis increased in regions having a guerrilla element
      in Chiapas. Modern immunodiagnostic techniques are used for control studies of
      cysticercosis and similar techniques were recently standardized for Trichinella
      spiralis detection. Low iodine values in children's urine were found in several
      Mexican states; therefore, use of iodized salt should be encouraged.

PMID- 12234524
TI  - Magnitude and impact of diarrheal diseases.
AB  - Among the increasingly unacceptable costs of the diseases of poverty are the
      largely unmeasured but potentially huge human and economic long-term costs of
      common tropical infectious diseases, especially those such as repeated
      dehydrating and malnourishing diarrheal diseases (and enteric infections, even
      without overt liquid stools) that are so prevalent in the developmentally
      critical first year or two of early childhood. We review here the high costs of
      diseases of poverty, increasing diarrhea morbidity (despite decreasing
      mortality), and new emerging evidence for long-term consequences of early
      childhood diarrhea on growth and on physical and cognitive development, effects
      that may translate into costly impairment of human potential and productivity.

PMID- 12234525
TI  - Molecular biology of rotavirus cell entry.
AB  - Rotaviruses, the leading cause of severe dehydrating diarrhea in infants and
      young children worldwide, are non-enveloped viruses formed by three concentric
      layers of protein that enclose a genome of double-stranded RNA. The entry of
      rotaviruses into epithelial cells appears to be a multistep process during which
      at least three contacts between the virus and cell receptors occur. Different
      rotavirus strains display different requirements to infect cells. Some strains
      depend on the presence of sialic acid on the cell surface; however, interaction
      with a sialic acid-containing receptor does not seem to be essential, because
      variants that no longer need sialic acid to infect the cells can be isolated from
      sialic acid-dependent strains. Comparative characterization of the sialic acid
      dependent rotavirus strain RRV, its neuraminidase-resistant variant nar3, and the
      human rotavirus strain Wa have allowed to show that alpha2beta1 integrin is used
      by nar3 as its primary cell attachment site, and by RRV in a second interaction
      subsequent to its initial contact with a sialic acid-containing cell receptor.
      These first two interactions are mediated by the virus spike protein VP4. After
      attaching to the cell, all three strains interact with integrin alphaVbeta3 and
      protein hsc70, interactions perhaps important for the virus to penetrate into the
      cell's interior. The cell molecules proposed to serve as rotavirus receptors have
      been found associated with cholesterol and glycosphingolipid-enriched lipid
      microdomains, and disorganization of these domains greatly inhibits rotavirus
      infectivity. We propose that the functional rotavirus receptor is a complex of
      several cell molecules most likely immersed in plasma membrane lipid
      microdomains.

PMID- 12234526
TI  - Molecular characterization and diagnosis of trypanosoma cruzi and T. rangeli.
AB  - The parasitic protozoan Trypanosoma cruzi infects an estimated 16 million
      individuals in Latin America. In a variable proportion of patients, this
      infection can result in a life-threatening cardiac or digestive pathology
      recognized as Chagas disease. In the majority of cases, the parasitemic phase of
      infection is transient and often goes unnoticed against the high background of
      endemic diseases present in the low-income groups usually affected by T. cruzi
      infection. Consequently, diagnosis of the infection by direct microscopic
      examination is rarely possible; therefore, routine serologic procedures as well
      as modern molecular techniques provide the most sensitive indicators of human
      infection.

PMID- 12234527
TI  - New approaches to improve a peptide vaccine against porcine Taenia solium
      cysticercosis.
AB  - Cysticercosis caused by Taenia solium frequently affects human health and rustic
      porciculture. Cysticerci may localize in the central nervous system of humans
      causing neurocysticercosis, a major health problem in undeveloped countries.
      Prevalence and intensity of this disease in pigs and humans are related to social
      factors (poor personal hygiene, low sanitary conditions, rustic rearing of pigs,
      open fecalism) and possibly to biological factors such as immunity, genetic
      background, and gender. The indispensable role of pigs as an obligatory
      intermediate host in the life cycle offers the possibility of interfering with
      transmission through vaccination of pigs. An effective vaccine based on three
      synthetic peptides against pig cysticercosis has been successfully developed and
      proved effective in experimental and field conditions. The well-defined peptides
      that constitute the cysticercosis vaccine offer the possibility to explore
      alternative forms of antigen production and delivery systems that may improve the
      cost/benefit of this and other vaccines. Encouraging results were obtained in
      attempts to produce large amounts of these peptides and increased its
      immunogenicity by expression in recombinant filamentous phage (M13), in
      transgenic plants (carrots and papaya), and associated to bacterial immunogenic
      carrier proteins.

PMID- 12234528
TI  - Flavivirus susceptibility in Aedes aegypti.
AB  - Aedes aegypti is the primary vector of yellow fever (YF) and dengue fever (DF)
      flaviviruses worldwide. In this review we focus on past and present research on
      genetic components and environmental factors in Aedes aegypti that appear to
      control flavivirus transmission. We review genetic relationships among Ae.
      aegypti populations throughout the world and discuss how variation in vector
      competence is correlated with overall genetic differences among populations. We
      describe current research into how genetic and environmental factors jointly
      affect distribution of vector competence in natural populations. Based on this
      information, we propose a population genetic model for vector competence and
      discuss our recent progress in testing this model. We end with a discussion of
      approaches being taken to identify the genes that may control flavivirus
      susceptibility in Ae. aegypti.

PMID- 12234529
TI  - Signal transduction in Entamoeba histolytica induced by interaction with
      fibronectin: presence and activation of phosphokinase A and its possible relation
      to invasiveness.
AB  - Interaction of Entamoeba histolytica trophozoites with extracellular matrix (ECM)
      proteins activates signaling pathways through G-protein-coupled receptors.
      Increments of adenylyl cyclase activity and cAMP produce a striking
      reorganization of actin into structures that apparently facilitate adhesive,
      locomotive, and secretory activities. The reorganization of actin is induced by
      phosphorylation of actin-associated proteins by diverse kinases activated during
      the signaling process. Although cAMP-dependent kinases have not yet been
      identified in this parasite, the activation of the adenylyl cyclase route and its
      effects on particular motility-related functions strongly suggest their presence.
      Phosphokinase A (PKA) was detected by phosphorylation of the specific substrate,
      kemptide, its further activation by cAMP, and its inhibition by H89. The
      catalytic subunit of the enzyme was identified by immunofluorescence microscopy
      and by immunoprecipitation. Adhesion and damage to cultured cells were monitored
      by FN-binding and cytotoxicity assays. A cAMP-dependent kinase activated by
      effectors and agonists of adenylyl cyclase and also during interaction of
      trophozoites with fibronectin (FN) was found. The enzyme is associated with small
      granules in the cytoplasm and upon activation, a fraction of its catalytic
      subunit with an Mr of 100 kDa was translocated to the nucleus, while another
      fraction was aggregated into big clusters. Activity and translocation were
      blocked by H89, a specific inhibitor of PKA. Trophozoites stimulated by dBcAMP or
      forskolin-formed lamellae and restructured actin, but no significant increase in
      their adhesion to FN was observed and only showed 10% stimulus in their capacity
      to damage target cells. Treatment with H89 decreased adhesion to 40% and caused
      80% inhibition in cell damage. These amebas showed altered organization of the
      actin structures induced by dBcAMP or FN. Our results support previous
      suggestions concerning the participation of PKA in the response elicited by the
      interaction of E. histolytica trophozoites with ECM proteins. They also indicate
      that adhesion and secretion in conjunction with motile activities are related to
      invasion processes.

PMID- 12234530
TI  - From noxiustoxin to scorpine and possible transgenic mosquitoes resistant to
      malaria.
AB  - Scorpion venom contains different types of peptides toxic to a variety of
      organisms whose molecular targets have been described as mainly ion-channels of
      excitable cells where they cause impairment of function. Based on mouse, cricket,
      and crustacean bioassays, specific toxins for each group of animals have been
      found. Chromatographic techniques were used to isolate and chemically
      characterize these peptides. One of the best-studied peptides is noxiustoxin, a
      39-amino acid residue-long peptide specific for K(+)-channels. Hadrurin is
      another scorpion venom peptide whose activity was shown to be bactericidal to a
      variety of species. Structural similarities of a newly discovered peptide
      (scorpine) with those of defensins and cecropins showed that scorpion venom
      contains peptides toxic to microorganisms and malaria parasites. Scorpine was
      shown to disrupt the sporogonic development of Plasmodium berghei. Using this
      system as a model for malaria, we introduced the gene of scorpine into a vector
      for generation of transgenic flies resistant to the infection by Plasmodium. The
      final aim of this work is to incorporate this gene under the promoter of
      proteolytic enzymes of digestive tract of mosquitoes for synthesis and liberation
      of toxic peptide(s) into stomach of freshly fed mosquitoes potentially carrying
      Plasmodium gametes. In this manner, a putative transgenic mosquito with these
      characteristics would secrete a toxic peptide with digestive enzymes into midgut,
      impairing proper development of Plasmodium, hence controlling malaria, one of the
      most important tropical diseases worldwide.

PMID- 12234531
TI  - Phenotypic diversity of antigen-presenting cells in ovine-afferent intestinal
      lymph.
AB  - The phenotypic and functional repertoire of antigen-presenting cells (APCs)
      remains incompletely characterized, particularly during the migratory phase of
      their life history, when these cells leave peripheral tissues and travel via
      afferent lymphatic vessels to regional lymph nodes. Lymphatic cannulation
      procedures were used to collect ovine APCs as they migrated from the mucosa of
      the small intestine to regional lymph nodes. A panel of 19 new monoclonal
      antibodies (mAbs) was produced to characterize surface molecules expressed on
      APCs by means of two-color flow cytometry and microscopy. Two broad patterns of
      mAb reactivity were evident. Twelve mAbs reacted almost exclusively with cells in
      the APC-gated region, because all these mAbs stained < 3% of cells in the
      lymphocyte-gated region. Within this group, some mAbs identified distinct subsets
      of dendritic cells (DCs). The second group of seven mAbs displayed high-intensity
      staining on cells in the APC-gated region but also reacted with variable numbers
      (4-26%) of cells in the lymphocyte-gated region. This indicates that molecules
      recognized by these mAbs are highly expressed on APCs but also occur on other
      lineages. When new mAbs were analyzed by two-color flow cytometry of cells in
      afferent intestinal lymph, a wide range of differences in reactivity were
      observed, especially on CD11b(+), CD11c(+), CD4(+), MHCII(+), and
      gammasigmaTCR(+) cells. Although molecular specificities of mAbs reported here
      remain undefined, marked heterogeneity of staining patterns indicates
      considerable phenotypic, and probably functional, diversity within APC population
      in afferent intestinal lymph. MAbs reported here will provide useful tools to
      explore these features further.

PMID- 12234532
TI  - Molecular taxonomy of trypanosomatids: some problems and pitfalls.
AB  - Trypanosomids appear to have attracted the particular attention of taxonomists,
      and a wealth of data from studies using a variety of techniques are available.
      There are, however, some potential pitfalls in such studies. A general problem in
      the taxonomy of Trypanosomatids resides in that only a small amount of its true
      diversity is reflected in the reduced number of isolates identified and studied
      from this family. An associated problem is that of confusion over the identity of
      the organisms. Other concerns include the problems of long branch attractions and
      mutational saturation, the loss of phylogenetic signal from the accumulation of
      overlapping mutations, and the fact that gene phylogeny cannot be equated with
      organism phylogeny and that organisms are more than just the sum of their genes.
      Additional complications can occur due to numerous cases of horizontal gene
      transfer between organisms. The use of a large sample of recent isolates from the
      field is also important so that the true diversity of these organisms is
      reflected in these studies, and bias due to selection, contamination, and
      misidentification when isolates have been maintained for long periods in culture
      is eliminated.

PMID- 12234533
TI  - The future outlook of antimalarial drugs and recent work on the treatment of
      malaria.
AB  - With the emergence of multidrug-resistant falciparum malaria, new drugs and drugs
      in combination are urgently needed. New antimalarial drugs investigated at the
      Hospital for Tropical Diseases of the Faculty of Tropical Medicine at Mahidol
      University in Bangkok, Thailand in recent years for treatment of uncomplicated
      and severe falciparum malaria are as follows: atovaquone, and artemisinin
      derivatives (artesunate, artemether, arteether, and dihydroartemisinin) combined
      with other antimalarials.Malarone, artemisinin derivatives combined with
      lumefantrine or doxycycline, and mefloquine combined with tetracycline or
      doxycycline have been evaluated with improvement of the cure rate in
      uncomplicated malaria. Artemisinin derivatives intravenously or intrarectally
      combined with mefloquine may be alternatives to intravenous quinine for treatment
      of severe malaria. In Thailand, drug treatment for uncomplicated malaria consists
      of the combinations or artesunate plus mefloquine or artemether plus lumefantrine
      or quinine plus tetracycline. In treatment of severe malaria, antimalarial drugs
      of choice are intravenous quinine or artemisinin derivatives.

PMID- 12234534
TI  - Wolbachia endosymbiotic bacteria of filarial nematodes. A new insight into
      disease pathogenesis and control.
AB  - Filarial nematodes are parasitic worms that cause some of the most devastating of
      all tropical diseases such as elephantiasis and river blindness. Studies on the
      inflammatory pathogenesis of filarial disease have shown that endotoxin-like
      activity derived from endosymbiotic Wolbachia bacteria is the major inflammatory
      stimulus of filarial nematodes. Wolbachia appear to have evolved as essential
      symbionts of their filarial nematode hosts. Antibiotic depletion of bacteria
      shows that they are required for normal fertility and development of the worm and
      may even protect the parasites from host immunity. In addition to the uncovering
      of a fascinating symbiotic relationship, this discovery means we can now consider
      using antibiotics as a new approach to the treatment of filarial diseases.

PMID- 12234535
TI  - Infectivity of resting spores of Massospora cicadina (Entomophthorales:
      Entomophthoraceae), an entomopathogenic fungus of periodical cicadas (Magicicada
      spp.) (Homoptera: Cicadidae).
AB  - Massospora cicadina Peck is a fungal pathogen of 13- and 17-year periodical
      cicadas (Magicicada spp.). In northwest Arkansas, during the spring 1998
      emergence of the 13-year periodical cicada, Magicicada tredecassini (Brood XIX),
      <1% of emerging cicadas were infected with the conidial stage of M. cicadina,
      similar to data collected from the same population in 1985. However, in northwest
      Arkansas plots treated with M. cicadina resting spores collected from infected 17
      year Magicicada septendecim cicadas (Brood IV) in 1997 from southern Iowa, 10
      months prior to the 1998 emergence in Arkansas, conidial stage infections of M.
      cicadina in 13-year Arkansas M. tredecassini cicadas increased significantly to
      10.6% (7.9% in males and 2.6% in females). These data suggest that M. cicadina
      resting spores do not require a dormancy of 13 or 17 years between cicada
      emergences. Instead M. cicadina resting spores appear to be capable of
      germinating and infecting periodical cicadas after less than 1 year. In addition,
      M. cicadina resting spores derived from one species (17-year M. septendecim
      cicadas) were infective for a second species (13-year M. tredecassini cicadas). A
      mean of 1.4 x 10(6)(SE = 1.8 x 10(5)) mature resting spores were produced per
      infected male M. septendecim.

PMID- 12234536
TI  - Pathogenic effects of bacteria isolated from larvae of Hylesia metabus Crammer
      (Lepidoptera: Saturniidae).
AB  - Hylesia metabus larvae are susceptible to several pathogens indigenous to the
      area in which they are found. Some larvae show symptoms characteristic of
      bacterial infection; they become flaccid and lethargic, and show a marked loss of
      appetite. We isolated and identified 29 bacterial strains from live, dead and
      experimentally infected H. metabus larvae, and evaluated their pathogenic
      activity. The bacteria which caused mortality in the larvae were: Pseudomonas
      aeruginosa (60-93.3%), Proteus vulgaris (20%), Alcaligenes faecalis, Planococcus
      sp. and Bacillus megaterium (10%), at doses of 3-4 x 10(7). Although P.
      aeruginosa is a well-known insect pathogen, this is the first report of its
      pathogenic activity on H. metabus. The potential risk to humans and low virulence
      make it unlikely that P. aeruginosa could be used in an augmentative biological
      control programme. However its natural incidence may be enhanced using parasites
      and predators of H. metabus as carriers.

PMID- 12234537
TI  - Use of tetracycline in larval diet to study the effect of Wolbachia on host
      fecundity and clarify taxonomic status of Trichogramma species in cured bisexual
      lines.
AB  - Endosymbionts of the genus Wolbachia were efficiently cured from Trichogramma
      species by incorporating 0.02% tetracycline into the artificial diet used to rear
      larvae. Use of this technique yielded stable cured lines (bisexual and
      arrhenotokous lines) in which no Wolbachia organisms were detected by PCR for up
      to 14 generations after curing. Four cured strains of Trichogramma pretiosum
      showed a significantly lower total fecundity compared to their Wolbachia-infected
      counterpart. However, the fecundity of a single cured strain of Trichogramma
      evanescens was similar to its Wolbachia-infected counterpart. These differences
      in the effect on fecundity may be due to differences between the Wolbachia
      strains infecting T. pretiosum or T. evanescens, providing additional evidence
      for the hypothesis that a specific interaction exists between some Trichogramma
      species and their Wolbachia symbionts. Tetracycline in larval diet was also used
      to generate bisexual strains of Trichogramma oleae and Trichogramma cordubensis
      so that these species could be crossed with the closely related species,
      respectively, T. pretiosum and T. evanescens, to test their compatibility. These
      crosses showed a lack of compatibility, validating maintenance of these as
      distinct species.

PMID- 12234538
TI  - Incidence of hemocytes and parasites in coastal populations of blue mussels
      (Mytilus edulis)--testing correlations with area, season, and distance to
      industrial plants.
AB  - Blue mussel hemocytes (cells with immunoresponse activities) are suggested as
      indicators of anthropogenic contamination. We compared hemocyte numbers,
      granulocytoma (aggregated hemocytes), and parasites among populations of mussels
      from different areas of Skagerrak (a north and a south), seasons (summer and
      autumn), and impact levels (close or far from industrial activities). Seasonal
      hemocyte numbers were larger in the north compared to the south. Northern
      unimpacted populations had higher hemocyte numbers than populations close to
      industries, while no differences were found in the south. More uneven tissue
      distributions were found in populations far from industries in the north area and
      in populations close to industries in the south area. Parasites were more common
      in northern mussels than in southern, but no relationship to impact level was
      found. Mussels with granulocytoma, however, were found in all populations from
      the impacted sites while in none of the other populations suggesting
      granulocytoma as a possible indicator of industrial impact.

PMID- 12234539
TI  - Molecular studies of co-formulated strains of the entomopathogenic fungus,
      Beauveria bassiana.
AB  - A 28S rDNA intron was used as a molecular marker to distinguish between two
      single spore strains of Beauveria bassiana, Bb123 and Bb151. When co-formulated
      and assayed against larvae of Galleria mellonella these strains exhibited no
      synergistic increase in virulence, rather Bb123 usually dominated. This study
      shows that the success of any strain to infect Galleria is dependent on the dose
      and method of inoculation (injection versus immersion). The result of co
      formulated strains grown on solid culture also showed that usually one strain
      dominated, i.e., strain displacement could happen both in vivo and in vitro. The
      speed by which one strain was displaced following successive sub-culturing on PDA
      partly depended on the ratio of Bb151 and Bb123. The co-formulated inoculum could
      widen the window over which parent strains would be active on different water
      activity media. Co-infection did result in heterokaryosis within the Galleria
      host. Molecular studies also showed that the heterokaryon was not stable and
      could revert back to the parent strain.

PMID- 12234540
TI  - Preliminary description of a new entomoparasitic nematode infecting Lutzomyia
      longipalpis sand fly, the vector of visceral leishmaniasis in the New World.
AB  - Phlebotomine sandflies are vectors of important pathogens world-wide, including
      Leishmania spp. in the Neotropics. Entomoparasites have been described from
      phlebotomines, including virus, bacteria, protozoa, fungi, nematodes, and mites,
      some of which are capable of killing the host. In the present study,
      interference, fluorescence, and scanning electron microscopies were used for the
      first time to detect and morphologically characterize a new entomoparasite
      infecting Lutzomyia longipalpis. Several filiform larvae and eggs in different
      stages were encountered in the abdomen of female and male insects. Pairs of large
      egg-bearing nematodes found within cyst-like structures or free in the hemocel
      accompanied by larvae could be the adult sexual stages. This entomoparasite
      infects sand flies naturally in the field. We believe that stress caused by the
      colonization procedure produced an increase in the infection rate among sand
      flies affecting their development. These findings could be applied to future
      biological control studies of sand fly vectors.

PMID- 12234541
TI  - Influence of antibiotics on the offspring production of the Wolbachia-infected
      parthenogenetic parasitoid Encarsia formosa.
AB  - Three different concentrations of the antibiotic tetracycline in honey were
      tested for their influence on the offspring production and longevity of the
      parasitoid wasp Encarsia formosa. Several earlier publications did not provide a
      conclusive answer on the effect that the Wolbachia have on these wasps. The
      results of our experiments show that at high tetracycline hydrochloride
      concentrations in honey (50mg/ml) the antibiotic is toxic to the females, all
      females died within three days after the antibiotic treatment. The concentration
      5mg/ml was less toxic although the treated females also lived shorter and
      produced less offspring than the control females. At the lowest tested
      concentration of 1mg/ml there was no significant difference either in offspring
      production or in longevity between the control and the treated females. The
      antibiotic treatment at both 5 and 1mg/ml resulted in exclusively male progeny
      after the first two days of oviposition. These results are consistent with the
      theory that in species in which all individuals are infected the Wolbachia should
      not impose a large fitness cost.

PMID- 12234542
TI  - Differences between the pathogenic processes induced by Steinernema and
      Heterorhabditis (Nemata: Rhabditida) in Pseudaletia unipuncta (Insecta:
      Lepidoptera).
AB  - Larvae of Pseudaletia unipuncta are moderately susceptible to infections caused
      by entomopathogenic nematodes, being a desirable host to study pathogenic
      processes caused by Heterorhabditis bacteriophora, Steinernema carpocapsae, and
      Steinernema glaseri and their associated bacteria. The ability of the infective
      stage of these nematodes to invade hosts is quite different. S. carpocapsae
      invades the highest number of insects and presents the highest penetration rate,
      followed by H. bacteriophora. Regression analysis between the number of insects
      parasitized and the number of IJs counted per insect, over time, showed a high
      correlation for S. carpocapsae whereas for H. bacteriophora it was low. Dose
      response was most evident at a concentration below 100 IJs per insect on H.
      bacteriophora, whereas on S. carpocapsae it was found for doses ranging from 100
      to 2,000 IJs. Student's t test analysis of dose-response showed parallel, yet
      unequal, slopes for both strains of H. bacteriophora, whereas distinct
      regressions were obtained for S. carpocapsae and S. glaseri, thus, evidencing
      each species develop a distinct pathogenic process. Insects injected with
      Photorhabdus luminescens died within 50 h after injection, whereas those treated
      with X. nematophila died much later. Moreover, the mortality in insects exposed
      to H. bacteriophora complex and injected with P. luminescens was close, but
      insects injected with bacteria died faster. Insect mortality in treatments with
      complexes S. carpocapsae and S. glaseri was significantly higher than that which
      was observed in insects injected with symbiotic bacteria.

PMID- 12234543
TI  - Toxicity of Bacillus thuringiensis insecticidal proteins for Helicoverpa armigera
      and Helicoverpa punctigera (Lepidoptera: Noctuidae), major pests of cotton.
AB  - The susceptibilities of the major pests of cotton in Australia, Helicoverpa
      armigera and Helicoverpa punctigera, to some insecticidal proteins from Bacillus
      thuringiensis were tested by bioassay. A commercial formulation, DiPel, and
      individual purified insecticidal proteins were tested. H. armigera was
      consistently more tolerant to B. thuringiensis insecticidal proteins than was H.
      punctigera, although both were susceptible to only a limited range of these
      proteins. Only Cry1Ab, Cry1Ac, Cry2Aa, Cry2Ab, and Vip3A killed H. armigera at
      dosages that could be considered acceptable. There was no significant difference
      in the toxicities of Cry1Fa and Cry1Ac for H. punctigera but Cry1Fa had little
      toxicity for H. armigera. The five instars of H. armigera did not differ
      significantly in their susceptibility to DiPel on the basis of LC(50). However,
      there were significant differences in the susceptibility to Cry1Ac and Cry2Aa of
      three strains of H. armigera. Bioassays conducted with Cry1Ac and Cry2Aa showed
      that there was a small but significant negative interaction between these delta
      endotoxins.

PMID- 12234544
TI  - Comparative activity of baculoviruses against the codling moth Cydia pomonella
      and three other tortricid pests of tree fruit.
AB  - The granulovirus of Cydia pomonella (L.) (CpGV) offers potential for selective
      control of codling moth. Two major limitations of CpGV are its narrow host range
      and lack of persistence in the orchard agroecosystem. The nucleopolyhedroviruses
      of the alfalfa looper Autographa californica (Speyer) (AcMNPV) and those of the
      celery looper Anagrapha falcifera (Kirby) (AfMNPV) have broad host ranges.
      Comparative assays of CpGV, AcMNPV, and AfMNPV against codling moth neonate
      larvae revealed a 54-93-fold greater susceptibility of codling moth to the
      granulovirus than to the two nucleopolyhedroviruses based on the LC(50) values
      for each virus. The LC(50)s for CpGV, AfMNPV, and AcMNPV were 32.7
      capsules/mm(2), 1.77 x 10(3) occlusion bodies (OBs)/mm(2), and 3.05 x
      10(3)OBs/mm(2), respectively. The LT(50) determined for AfMNPV using an
      approximate LC(95) of the virus against neonate larvae was 3.6 days. Histological
      examination of tissues in moribund codling moth larvae that had been treated with
      AfMNPV revealed the presence of nonoccluded and unenveloped virus rods in midgut
      tissue. Neither OBs nor signs of infection were detected in other tissues. The
      activity of AfMNPV was also evaluated in three other tortricid apple pests
      (obliquebanded leafroller, Choristoneura rosaceana (Harris); Pandemis leafroller,
      Pandemis pyrusana Kearfott; and the oriental fruit moth, Grapholitha molesta
      (Busck)). Codling and Oriental fruit moths were significantly more susceptible to
      AfMNPV than were the two leafroller species.

PMID- 12234545
TI  - Measures of Bacillus thuringiensis persistence in the corn whorl.

PMID- 12234546
TI  - Examining time trends in the Oldowan technology at Beds I and II, Olduvai Gorge.
AB  - The lithic analysis of the Bed I and II assemblages from Olduvai Gorge reveals
      both static and dynamic time trends in early hominids' technology from 1.8 to 1.2
      m.y.a. The Bed I Oldowan (1.87-1.75 m.y.a.) is characterized by the least effort
      strategy in terms of raw material exploitation and tool production. The inclusion
      of new raw material, chert, for toolmaking in the following Developed Oldowan A
      (DOA, 1.65-1.53 m.y.a.) facilitated more distinctive and variable flaking
      strategies depending on the kind of raw materials. The unique characters of DOA
      are explainable by this raw material factor, rather than technological
      development of hominids. The disappearance of chert in the subsequent Developed
      Oldowan B and Acheulian (1.53-1.2 m.y.a.) necessitated a shift in tool production
      strategy more similar to that of Bed I Oldowan than DOA. However, the evidence
      suggests that Bed II hominids might have been more skillful toolmakers, intensive
      tool-users, and engaged in more active transport of stone tools than the Bed I
      predecessors. Koobi Fora hominids maintained a more static tool-using behavior
      than their Olduvai counterparts due mainly to a stable supply of raw materials.
      They differed from Olduvai hominids in terms of less battering of cores,
      consistent transport behavior, and few productions of side-struck flakes,
      indicating a regional variation of toolmaking and using practice. However, they
      shared with Olduvai hominids a temporal trend toward the production of larger
      flakes from larger cores after 1.6 m.y.a. Increased intake of animal resources
      and the expansion of ranging area of Homo ergaster would have led to the
      development of technological organization. Technological changes in the Oldowan
      industry are attested at Olduvai Gorge, Koobi Fora, and Sterkfontein, suggesting
      that it was a pan-African synchronous phenomenon, beginning at 1.5 m.y.a.

PMID- 12234547
TI  - Pairwise difference analysis in modern human origins research.
AB  - Pairwise difference analysis is a phenetic method that groups taxa on the basis
      of the number of differences they exhibit. Recently, pairwise difference analysis
      has been used to investigate the phylogenetic relationships of hominid fossils at
      the centre of the modern human origins debate. It has been argued that the
      results of these analyses disprove the African replacement model of modern human
      origins, and support instead its competitor, the multiregional evolution model.
      However, this inference is problematic because the ability of pairwise difference
      analysis to recover phylogenetic information from morphological data has not been
      demonstrated. With this in mind, we conducted pairwise difference analyses of
      craniodental and soft tissue evidence from a group of extant primates for which a
      reliable molecular phylogeny is available, the hominoids. We found that the
      phylogenies yielded by the pairwise difference analyses were incompatible with
      the molecular phylogeny for the group. Given the robustness of the molecular
      phylogeny, these results suggest that pairwise difference analysis cannot be
      relied on to generate reliable estimates of primate phylogeny from morphological
      data. The corollary of this is that the results of published pairwise difference
      analyses of hominid fossils are not informative regarding the origin of modern
      humans.

PMID- 12234548
TI  - Notharctine primates (Adapiformes) from the early to middle Eocene (Wasatchian
      Bridgerian) of Wyoming: transitional species and the origins of Notharctus and
      Smilodectes.
AB  - Notharctine adapiform primates are an abundant element of early (Wasatchian) and
      middle (Bridgerian) Eocene faunal assemblages from the western interior of North
      America. Early Eocene notharctine samples are dominated by Cantius with Pelycodus
      and Copelemur being much rarer and more restricted in their geographic
      distribution. Cantius is replaced in the middle Eocene by Notharctus and
      Smilodectes, both of which are common but less widespread, being best known from
      southwestern Wyoming. The origin of these two middle Eocene taxa has not been
      well understood, due to a lack of transitional Wasatchian-Bridgerian notharctine
      faunal samples or because known samples had not been adequately studied. Field
      work at South Pass in the Greater Green River Basin has produced a relatively
      large sample of earliest Bridgerian notharctines. Combining this sample with a
      large, but previously under-studied, sample of notharctines from the latest
      Wasatchian and earliest Bridgerian in the Wind River Basin has clarified the
      relationships among Notharctus,Smilodectes, and earlier occurring notharctines.
      Notharctus first appears in the latest Wasatchian (Wa7), represented by N.
      venticolus. Phylogenetic analysis supports a Notharctus clade that shares sister
      taxon status with Cantius nunienus and indicates that Notharctus arose through
      bifurcation of the lineage containing the last common ancestor of C. nunienus and
      Notharctus. The origins of Smilodectes are less clear. Phylogenetic analysis
      supports a clade consisting of Smilodectes and Copelemur, but the origins of both
      taxa are not established as yet. North American notharctines are typified by
      relatively low taxonomic diversity, but relatively high abundance and high dental
      morphological variation (disparity). These attributes are opposite to those of
      North American omomyids, reflecting differences in ecomorphospace between these
      two primate radiations.

PMID- 12234549
TI  - The Gravettian occipital bone from the site of Malladetes (Barx, Valencia,
      Spain).
AB  - The juvenile occipital bone from the site of Malladetes in Valencia (Spain) is
      described and compared with other European Pleistocene representatives of the
      genus Homo. This specimen derives from a Gravettian cultural context and has been
      AMS radiocarbon-dated to 25,120 +/- 240 years BP. As such, it provides evidence
      on early modern human anatomy from the Central Mediterranean region of the
      Iberian peninsula. The clear evidence for a late survival of Neandertals in
      southern Iberia, has led to considerable debate surrounding the biological and
      cultural interactions between these Pleistocene humans and their early modern
      human successors, and it is within this context that the Malladetes specimen
      represents an important contribution to the discussion. The recently discovered
      Upper Paleolithic infant from the site of Lagar Velho in Portugal is said to show
      a mosaic of Neandertal and early modern human characteristics throughout the
      skeleton and is argued to represent the strongest evidence yet recovered in favor
      of hybridization between these two Pleistocene populations. Our analysis of the
      Malladetes occipital, however, reveals no evidence of Neandertal genetic
      influence.

PMID- 12234550
TI  - The palaeoecology of the Upper Ndolanya Beds at Laetoli, Tanzania.
AB  - The palaeoecology of the fauna from the Ndolanya Beds, Laetoli, Tanzania, has
      been analysed to reconstruct the environment of this 2.6 Ma site. Community
      profiles have been constructed in relation to three variables that carry
      ecological meaning: body weight, locomotor adaptations and feeding preferences.
      Comparing the similarities and differences in the structure of the fossil faunas
      with those of modern environments allows us to draw inferences about
      palaeoenvironmental conditions, and this is based on a comparative dataset of 15
      modern environments (44 localities) covering a wide range of climatic and
      ecological conditions across Asia, Africa and Central America. In addition, 16
      fossil sites in East and South Africa have been analysed in the same way, and
      both sets of comparative data have been used as the basis for comparison with an
      ecological diversity analysis of the fauna from the Upper Ndolanya Beds. The
      Ndolanya fauna is characterized by a predominance of medium to large sized
      terrestrial and herbivorous species. There is evidence of taphonomic bias that
      eliminated many of the smaller species. A comparison of multivariate analyses of
      23 selected modern localities conducted both with and without the small species
      included, indicates that the loss of these species does not adversely influence
      the results of an ecological diversity analysis. The evidence suggests that at
      the time of the deposition of the Ndolanya Beds the Laetoli region was a semi
      arid bushland. This is considerably drier and more open than is suggested for the
      earlier Laetolil Beds.

PMID- 12234551
TI  - The late Neandertal supraorbital fossils from Vindija Cave, Croatia: a biased
      sample?
AB  - The late Neandertal sample from Vindija (Croatia) has been described as
      transitional between the earlier Central European Neandertals from Krapina
      (Croatia) and modern humans. However, the morphological differences indicating
      this transition may rather be the result of different sex and/or age compositions
      between the samples. This study tests the hypothesis that the metric differences
      between the Krapina and Vindija supraorbital samples are due to sampling bias. We
      focus upon the supraorbital region because past studies have posited this region
      as particularly indicative of the Vindija sample's transitional nature.
      Furthermore, the supraorbital region varies significantly with both age and sex.
      We analyzed four chords and two derived indices of supraorbital torus form as
      defined by Smith & Ranyard (1980, Am. J. phys. Anthrop.93, pp. 589-610). For each
      variable, we analyzed relative sample bias of the Krapina and Vindija samples
      using three sampling methods. In order to test the hypothesis that the Vindija
      sample contains an over-representation of females and/or young while the Krapina
      sample is normal or also female/young biased, we determined the probability of
      drawing a sample of the same size as and with a mean equal to or less than
      Vindija's from a Krapina-based population. In order to test the hypothesis that
      the Vindija sample is female/young biased while the Krapina sample is male/old
      biased, we determined the probability of drawing a sample of the same size as and
      with a mean equal or less than Vindija's from a generated population whose mean
      is halfway between Krapina's and Vindija's. Finally, in order to test the
      hypothesis that the Vindija sample is normal while the Krapina sample contains an
      over-representation of males and/or old, we determined the probability of drawing
      a sample of the same size as and with a mean equal to or greater than Krapina's
      from a Vindija-based population. Unless we assume that the Vindija sample is
      female/young and the Krapina sample is male/old biased, our results falsify the
      hypothesis that the metric differences between the Krapina and Vindija samples
      are due to sample bias.

PMID- 12234552
TI  - The impact of political conflict on moral maturity: a cross-national perspective.
AB  - This cross-national study of moral reasoning among adolescents in Northern
      Ireland, Scotland and the Republic of Ireland, addresses the problem of possible
      moral truncation in Northern Ireland due to the political conflict. The
      Sociomoral Reflection Measure-Short Form (SRM-SF; Gibbs et al. (1992) Moral
      Maturity: Measuring the Development of Sociomoral Reflection. Englewood Cliffs,
      NJ: Erlbaum. was presented to a proportionate stratified sample of 14-15 year
      olds (n = 613) from three locations including a small town, large town and city
      in each country to control for urbanization. This adolescent sample consisted of
      participants from both of Northern Ireland's religious communities and was
      matched for age and sex. Analysis of the results suggested that despite the
      violent atmosphere over the last 30 years, the Northern Irish adolescents were
      not developmentally delayed in moral terms as previously feared (Fraser (1972)
      Special Education,61, 6-8; Fields (1973). A Society on the Run: A Psychology of
      Northern Ireland. Harmondsworth, Middlesex: Penguin; (1976) Northern Ireland:
      Society Under Siege. New Brunswick and London: Transaction Books; Lyons (1973)
      The Northern Teacher, 19-30)

PMID- 12234553
TI  - Knowledge, use of and attitudes towards peer support: a 2-year follow-up to the
      Prince's Trust survey.
AB  - This present study investigated how school peer support systems studied 2 years
      earlier in a survey funded by The Prince's Trust have evolved. In all, 413 pupils
      (actual and potential users of the systems) aged 13-14 (Year 9--Y9) and 15-16
      (Year 11--Y11), 34 teachers in charge of systems and 80 peer supporters in 35
      secondary schools were interviewed using structured schedules for the pupils and
      semi-structured ones for the teachers and peer supporters. All of these
      interviews focussed on the respondents' perceptions and experiences of the
      school's peer support system, including: the perceived benefits to users of the
      system; benefits to peer supporters; problems with the system and the attempts
      made to overcome them. There was widespread support for the systems and a strong
      sense that both teachers and peer supporters were increasingly confident about
      the value of their service. However, some problems remain, notably with regard to
      gender. The study documents difficulties in the recruitment and retention of boys
      as peer supporters because of peer pressure to conform to a "macho" image. The
      issue is discussed and some solutions presented.

PMID- 12234554
TI  - Victimizing behaviour among juvenile and young offenders: how different are
      perpetrators?
AB  - This study examined the victimizing behaviours of incarcerated juvenile and young
      offenders. A total of 108 juveniles and young offenders completed questionnaires
      relating to victimizing behaviours and were administered the Custodial Adjustment
      Questionnaire (CAQ: Thornton, 1987 In Applying Psychology to Imprisonment: Theory
      and Practice, McGurk B.J., Thornton, D. and Williams, M. (Eds). London: HMSO, pp.
      445-465) and Hostility and Direction of Hostility Questionnaire (HDHQ: Caine et
      al., 1967. Manual of the Hostility and Direction of Hostility Questionnaire.
      London: University of London press). It was found that 50.9% of all respondents
      reported victimizing others, with verbal assaults and threats being the most
      common form of such behaviours. Furthermore, staff-identified "victimizers" were
      significantly more likely to report victimizing behaviour than the rest of the
      sample. Those who had been in custody longer were more likely to report
      victimizing others, as were younger offenders (15-17-year olds as compared to 18
      21-year olds). Victimizers were also more likely to report having previously
      experienced victimization themselves. On the psychometric measures, self-reported
      victimizers scored significantly higher on the deviance sub-scale of the CAQ, and
      on a number of the sub-scales of the HDHQ. These findings are discussed in terms
      of previous literature and their practical implications considered.

PMID- 12234555
TI  - Heterosexual risk behaviour among young teenagers in Scotland.
AB  - This paper provides the first detailed data on the heterosexual sexual experience
      of a large sample of 14-year-olds in Scotland. The paper investigates the
      prevalence, nature and correlates of early heterosexual intercourse, and the
      extent and correlates of condom use. Questionnaires were administered in 24
      schools under examination conditions (N=7630). Eighteen per cent of boys and 15%
      of girls reported having had intercourse. Sixty per cent reported condoms were
      "used throughout". The most important correlate of sexual experience was low
      level of parental monitoring; the key predictor for condom use was whether or not
      the respondent talked to their partner about protection before having sexual
      intercourse.

PMID- 12234557
TI  - Changes in adolescents' and mothers' autonomy and connectedness in conflict
      discussions: an observation study.
AB  - Behaviour in conflicts in 76 dyads of mothers and their 11-16-year-old
      adolescents was observed twice in a 2-year interval. In concordance with
      individuation theory (Youniss and Smollar, 1985, Adolescent relations with
      mothers, fathers and friends. Chicago, IL: University of Chicago Press), we found
      an increase across assessments in adolescents' autonomy. In accordance with
      Steinberg's (1990, At the Threshold: The Developing Adolescent, Feldman, S. and
      Elliott, G. (Eds). Cambridge, MA: Harvard University Press, pp. 255-276)
      developmental theory, we observed a decrease of connectedness with their mothers
      in younger adolescents and an increase of connectedness in older adolescents.
      Changes in mothers' connectedness with their children paralleled the changes in
      adolescents, but only the increase of connectedness of mothers of older
      adolescents was statistically significant. Higher levels of connectedness were
      observed in mother-daughter than in mother-son dyads. In addition, female
      adolescents were more successful in changing their mothers' position than their
      male age-peers. As decreases in connectedness were moderate, it is still true
      that some connectedness between adolescents and parents is maintained across
      adolescence, as suggested by individuation theory.

PMID- 12234556
TI  - Evaluation of a comprehensive AIDS education curriculum in Hungary--the role of
      good educators.
AB  - The aim of this research was to evaluate a school-based AIDS education programme
      in Eastern Europe. Four evaluation segments were undertaken: process and outcome
      evaluations of the training of AIDS educators and of the educational activities
      for students. While most AIDS education curricula focus on the content of the
      education, our findings demonstrate that other aspects--including the
      characteristics of those educators who appear to be most effective, the way in
      which education is affected by teachers' attitudes, and the cultural implications
      of transferring programmes from one country to another--also need to be
      considered, especially in international environments.

PMID- 12234558
TI  - Children's satisfaction with out-of-home care in South Australia.
AB  - Two studies were undertaken to assess children's satisfaction with their current
      placement experiences in South Australian alternative care. A total of 99
      children with a mean age of 11 years were interviewed while still in care. Over
      80 per cent of children reported being satisfied with both their case-worker and
      their placement, although children in residential (group) care reported being
      less satisfied than their counterparts in foster care. Foster homes were
      generally considered secure, happy and supportive, and case-workers were
      considered helpful, caring and willing to listen. Comparisons of background
      characteristics, measures of adjustment and demographic characteristics suggested
      that the samples interviewed were highly representative of the population of
      children referred for placements during the study period.

PMID- 12234559
TI  - The measurement of puberty: a review.
AB  - This paper has two main objectives. Firstly, to review the feasibility and
      validity of the various methods that have been used to measure puberty. With an
      appreciation of these measurement issues, the second objective is to summarize
      the evidence-base as to whether the age at menarche and the age at onset of
      puberty has decreased in recent years. In consideration of these methodologies,
      all of which report different levels of reliability and validity, it is only
      possible at present to draw inferences about possible changes in pubertal age and
      onset. Moreover, the wide variations in sample size, selection of participants
      (usually non-random), and study design reported in the reviewed studies have
      compounded this situation further. The paper closes by providing a summary of the
      findings which will be of relevance to those intending to critically review the
      current evidence surrounding age of puberty, as well as those set on carrying out
      future research into this area.

PMID- 12234560
TI  - Adolescents carrying handguns and taking them to school: psychosocial correlates
      among public school students in Illinois.
AB  - The current study sought to examine psychosocial correlates of adolescents
      carrying a handgun and taking a handgun to school. Survey participants were
      approximately 22,000 6th, 8th, and 10th grade public school students from
      throughout Illinois. Results showed that the strongest correlates of handgun
      carrying behaviours were variables directly associated with handguns and
      violence, both behaviours and beliefs, as well as delinquency variables. These
      findings have many implications for intervention by parents, schools, and policy
      makers to reduce the incidence of adolescent handgun carrying and taking a
      handgun to school.

PMID- 12234563
TI  - Cancer and thromboembolic disease: how important is the risk of thrombosis?
AB  - The overall incidence of postoperative DVT in patients with cancer is twice as
      high as in cancer-free patients. Immobilisation and chemotherapy increase the
      risk of thrombosis as does the insertion of central venous lines. Patients with
      cancer who have established thrombosis exhibit a remarkably high risk of
      recurrent thromboembolism, particularly in the first months after the
      interruption of anticoagulant treatment: the risk is double that of non-cancer
      patients. Even during anticoagulant treatment, the cumulative incidence of
      recurrent thromboembolism is 3.5 times higher in patients with malignancy than in
      cancer-free patients. Conversely, there is a high rate of cancer detection in
      patients with idiopathic VTE: the risk of concomitant cancer is approximately
      four times higher in these patients than in those with thrombosis triggered by
      known factors. Extensive screening for cancer in patients with idiopathic venous
      thrombosis allows early detection of malignancies and identification of
      malignancy at an early stage.

PMID- 12234564
TI  - Cancer and thromboembolic disease: pathogenic mechanisms.
AB  - Almost all types of cancer are associated with an activation of coagulation.
      However, elevation of haemostatic markers of coagulation does not predict venous
      thrombosis. Multiple and interdependent processes between the tumour and the
      patient induce a hypercoagulable state. Tumour procoagulant activity, host
      inflammatory responses and extrinsic factors are involved. Tumour cells express
      the procoagulants, tissue factor and cancer procoagulant. They also release
      inflammatory cytokines and vascular endothelial growth factor, substances that
      enhance procoagulant activity and angiogenesis. Tumour-induced coagulation is
      intrinsically involved with tumour growth, angiogenesis and metastasis.

PMID- 12234565
TI  - Preventing thromboembolic complications in cancer patients after surgery: a role
      for prolonged thromboprophylaxis.
AB  - Patients undergoing major abdominal surgery for malignancy are at particularly
      high risk of developing VTE. Extra protection against this can be given to
      patients with cancer by using a higher dose of LMWH than normally used for
      prophylaxis, with no increase in bleeding complications. Despite
      thromboprophylaxis with high-dose LMWH for the first postoperative week, the rate
      of late VTE is estimated to be between 10% and 20%. A meta-analysis of two
      studies using dalteparin or enoxaparin has shown that prolonging
      thromboprophylaxis for a further 3 weeks significantly reduces the risk of late
      occurring VTE by 62%. Thromboprophylaxis with LMWH for at least one month should
      be considered in patients undergoing surgery for malignant disease.

PMID- 12234566
TI  - Managing thromboembolic disease in the cancer patient: efficacy and safety of
      antithrombotic treatment options in patients with cancer.
AB  - Management of thromboembolic disease in patients with cancer can be challenging.
      Patients with cancer who have established thrombosis are at increased risk of
      recurrent VTE and of anticoagulant-associated bleeding compared to patients with
      no cancer. The optimal treatment of VTE in patients with cancer should lower the
      risk of recurrent VTE without increasing the risk of bleeding and ideally improve
      a patient's quality of life. Initial treatment of VTE in patients with cancer
      should be with LMWH, which may be administered, subcutaneously, at home. The
      current standard of care for long-term treatment of VTE remains oral
      anticoagulant, which should be administered for as long as the cancer is active.
      However, the use of oral anticoagulants can be problematic in these patients due
      to possible anorexia and vomiting. The efficacy and safety of long-term treatment
      of VTE in cancer patients with LMWH is currently under investigation.

PMID- 12234567
TI  - Can low-molecular-weight heparins improve outcome in patients with cancer?
AB  - Patients with cancer who experience a thrombotic episode have a greater mortality
      rate than those without thromboembolic complications. VTE appears to be a more
      aggressive disease in patients with cancer, who often have a greater thrombus
      burden than cancer-free patients. An increased risk of VTE associated with
      certain tumour types, such as ovarian cancer, may be linked to overexpression of
      coagulation proteases. Retrospective trial data suggest that LMWHs prolong
      survival in some cancers. LMWHs are effective both in the prevention and
      treatment of thromboembolic disease in patients with cancer and this may be their
      most important effect, contributing to an improved outcome. They may also act by
      inhibiting coagulation proteases, which affect tumour biology or by a direct
      effect on malignant cells. A prospective trial to investigate the effect of long
      term treatment with the LMWH dalteparin on survival of patients with advanced
      cancer is currently being evaluated.

PMID- 12234568
TI  - What is the role for antithrombotics in cancer care? Interactive session with
      panel discussion.

PMID- 12234569
TI  - Ethnomedical knowledge of plants used by Kunabi Tribe of Karnataka in India.
AB  - Therapeutic effects and medicinal efficacy of the wild herbs were identified and
      administered by the tribal people to cure various ailments. Recently, the
      practice of herbal medicine has been diminishing, which may lead to the loss of
      valuable information about healing herbs. The Uttara Kannada District of
      Karnataka in India is one of the rich biodiversity centers of Western Ghats. Many
      tribes like Gowlis, Siddis, Halakki Okkaligas and Kunabis inhabit the semi
      evergreen forests of the District. The mixed marathi speaking Kunabis have
      migrated from Goa and settled here a long time back and are even today without
      modern facilities. Thus, in the way of revitalization of traditional herbal
      medicines, it is an effort to record the valuable ethnomedical knowledge of the
      tribe Kunabis of Uttara Kannada District in Karnataka. A total of 45 species of
      plants used by Kunabi community people are described here based on an
      ethnomedical field survey. These plants belong to 26 families and are used to
      treat a wide range of discomforts like fever, cough, skin diseases, rheumatism,
      snakebite, jaundice, dysentery, etc.

PMID- 12234570
TI  - Structure of a novel diterpenoid ester, fritillahupehin from bulbs of Fritillaria
      hupehensis Hsiao and K.C. Hsia.
AB  - A new diterpenoid ester, fritillahupehin (1) together with three known fatty
      acids: palmitic acid (2), lignoceric acid (3) and azelaic acid (4) were isolated
      from the bulbs of Fritillaria hupehensis Hsiao and K.C. Hsia. The structure of
      fritillahupehin has been established to be ent-kauran-16beta-yl lignocerate by
      means of spectroscopic and chemical evidence. Compounds 2-4 were isolated from
      Fritillaria sp. for the first time.

PMID- 12234571
TI  - Tannin composition of barbatimao species.
AB  - A comparative study of tannin composition of three species known as barbatimao
      (Stryphnodendron adstringens, Stryphnodendron polyphyllum and Dimorphandra
      mollis) was developed by TLC, hydrolysis followed by PC, and colorimetry.
      Principal component analysis of the data obtained showed strong differentiation
      between the genus Dimorphandra and Stryphnodendron. Additionally, barks from the
      two Stryphnodendron sp. also presented considerable differences in the tannin
      structure.

PMID- 12234572
TI  - The genus Hypericum--a valuable resource of anti-Staphylococcal leads.
AB  - In the present study, extracts of 34 species and varieties of the genus Hypericum
      were screened for activity against a clinical isolate of methicillin-resistant
      Staphylococcus aureus, which in addition possessed a multidrug efflux mechanism
      conferring a high level of resistance to therapeutically useful antibiotics.
      Thirty-three of the 34 chloroform extracts showed significant activity in a disk
      diffusion assay, and five extracts had minimum inhibitory concentrations of 64
      microg/ml, indicating that this genus has great potential to yield compounds with
      potent activity against multidrug-resistant bacteria.

PMID- 12234573
TI  - Effect of extract of medicinal plants on the labeling of blood elements with
      Technetium-99m and on the morphology of red blood cells: I--a study with
      Paullinia cupana.
AB  - Drugs can alter the labeling and the morphology of red blood cells. As Paullinia
      cupana is used in popular medicine, we evaluated its influence on the labeling
      process using technetium-99m (Tc-99m). Blood was incubated with P. cupana,
      stannous chloride and Tc-99m. Samples were centrifuged and plasma (P) and blood
      cells (BC) were separated and precipitated with trichloroacetic acid. Soluble
      (SF) and insoluble fractions (IF) were isolated. The morphology of the blood
      cells was evaluated under an optical microscope. The results showed a significant
      (P = 0.05) decrease in the uptake of radioactivity for the RBC (97.93 +/- 0.74 to
      36.90 +/- 4.71%), in IF-P and in IF-BC due to P. cupana extract. The study of the
      morphology of the RBC revealed alterations in the shape of these cells. We
      suggest that the P. cupana effect could be explained by an inhibition of the
      stannous and pertechnetate ions or oxidation of the stannous ion or by damages in
      the plasma membrane.

PMID- 12234574
TI  - Stilbenes from Sphaerophysa salsula.
AB  - A new stilbene, (trans)-4-[2-(3, 5-dimethoxyphenyl) ethenyl]-1,2-benzenediol (1),
      was isolated from the whole herbs of Sphaerophysa salsula, together with (trans)
      4-[2-(3, 5-dimethoxy phenyl) ethenyl]-2-methoxyphenol (2) and daucosterol. The
      structure of 1 was determined on the basis of spectroscopic evidences.

PMID- 12234575
TI  - Iristectorone K, a novel monocyclic triterpene ester from Iris germanica rhizomes
      growing in Turkey.
AB  - A new monocyclic triterpene ester (1) was isolated from the rhizomes of Iris
      germanica from Turkey. Structure elucidation of compound (1) was carried out by
      the combined application of HMQC, HMBC, DEPT, COSY and NOESY experiments and
      named as iristectorone K.

PMID- 12234576
TI  - Saponins from Styrax officinalis.
AB  - Three triterpene saponins named Styrax-saponin A-C (1-3) were found in pericarps
      of Styrax officinalis together with the deacylsaponin (4). Structural
      determinations were achieved using 1D-, 2D-NMR and mass spectrometry.

PMID- 12234577
TI  - Antibacterial and antifungal activities of Dracontomelon dao.
AB  - The crude methanolic extracts of the leaves, stem and root barks of
      Drancantomelon dao and their subsequent partitioning (petrol, dichloromethane,
      ethyl acetate, butanol) gave fractions which demonstrated a very good level of
      broad spectrum antibacterial activity. The dichloromethane and butanol fractions
      of the leaf were the most active. Only the leaf fractions had antifungal
      activity, particularly the dichloromethane and butanol.

PMID- 12234578
TI  - Antibacterial, antifungal activity of Harpullia petiolaris.
AB  - The methanol extracts of Harpullia petiolaris, leaves, stem and root barks and
      heartwoods were fractionated into petrol, dichloromethane, ethyl acetate and
      butanol. All fractions exhibited antibacterial activity.

PMID- 12234579
TI  - Antimicrobial and antifungal activity of crude extracts and isolated saponins
      from Astragalus verrucosus.
AB  - The antimicrobial and antifungal properties of several crude extracts and pure
      saponins, astraverrucins I-VI, from the aerial parts of Astragalus verrucosus
      were investigated by the disc diffusion method. Antimycotic activity was observed
      on more polar extracts, but only one saponin showed an appreciable activity.

PMID- 12234580
TI  - Antinociceptive and antidiarrhoeal activity of Zanthoxylum rhetsa.
AB  - The methanolic extract of the Zanthoxylum rhetsa Roxb. stem bark, given by oral
      route to mice at doses of 250 and 500 mg/kg, significantly reduced the abdominal
      contraction induced by acetic acid and the diarrhoeal episodes induced by castor
      oil in mice.

PMID- 12234581
TI  - Antimicrobial activity of Bridelia ferruginea leaves extracts.
AB  - Methanol, ethyl acetate, and hexane extracts of Bridelia ferruginea leaves
      exhibited significant activity against Pseudomonas frutescens, Bacillus subtilis,
      Echerichia coli, Staphylococcus aureus and Streptococcus faecalis.

PMID- 12234582
TI  - In vitro antiviral activity of thirty-six plants from La Reunion Island.
AB  - Methanol extracts of 36 medicinal plants from La Reunion Island were evaluated
      against two viruses: Herpes simplex type 1 (HSV-1) and poliovirus type 2 (PV).
      Five of them showed an effect against HSV-1 and five against PV, Senecio
      ambavilla being inhibitor for both viruses.

PMID- 12234583
TI  - Hyperglycemic effect of leaves of Mimosa pudica Linn.
AB  - Ethanolic extract of Mimosa pudica leaves given by oral route to mice at a dose
      of 250 mg/kg showed a significant hyperglycemic effect.

PMID- 12234584
TI  - Isolation and structural elucidation of 3,4',5,7-tetraacetyl quercetin from Adina
      cordifolia (Karam ki Gaach).
AB  - 3,4',5,7-tetraacetyl quercetin (1) was isolated from the heartwood of Adina
      cordifolia. The structure was elucidated on the basis of spectral evidence.

PMID- 12234585
TI  - Roraimine: a bisbenzylisoquinoline alkaloid from Cissampelos sympodialis roots.
AB  - The roots of Cissampelos sympodialis yielded Roraimine (1), a novel
      bisbenzylisoquinoline alkaloid and liriodenine (2), a known oxoaporphine
      alkaloid.

PMID- 12234586
TI  - 3-[(123)I]Iodo-alpha-methyl-L-tyrosine: uptake mechanisms and clinical
      applications.
AB  - 3-[(123)I]Iodo-alpha-methyl-L-tyrosine (IMT) is an artificial amino acid which
      has gained considerable interest in Nuclear Medicine in the last two decades.
      Although the tracer is not incorporated into proteins it exhibits high uptake in
      brain tumors and appears to be a valuable tool especially for the diagnostic
      evaluation and therapy planning of patients with cerebral gliomas. In this paper
      the present knowledge of the uptake mechanisms and the clinical applications of
      IMT are reviewed and the clinical perspectives discussed.

PMID- 12234587
TI  - Benzofuran derivatives as Abeta-aggregate-specific imaging agents for Alzheimer's
      disease.
AB  - The purpose of this study is to develop potential I-123 labeled diagnostic
      imaging agents targeting amyloid plaques in Alzheimer's disease (AD). Formation
      and accumulation of aggregates of beta-amyloid (Abeta) peptides in the brain are
      critical factors in the development and progression of AD. Small molecule-based
      benzofuran derivatives were designed and synthesized. Both 5- and 6
      iodobenzofuran derivatives displayed excellent competition for I-125 TZDM binding
      to Abeta40 aggregates with K(i) values in the subnanomolar range. The
      radioiodinated ligands, with a high specific activity, were successfully prepared
      through an iododestannylation reaction from the corresponding tributyltin
      derivatives using hydrogen peroxide as the oxidant in high yields (60-80%) and
      with high radiochemical purities (greater than 95%). After an iv injection, all
      four radioiodinated ligands displayed high brain uptakes ranging from 0.5 to 1.5%
      initial dose/organ in normal mice. The radioactivity washed out from the mouse
      brain slowly (less than 50% at 2 h post injection), suggesting high in vivo non
      specific binding. In conclusion, the benzofuran ligands displayed excellent
      binding affinity for Abeta aggregates. The long retention of these ligands in the
      normal mouse brain suggests that there may be high binding for these probes in
      the brain not associated with Abeta plaques. Additional modifications are
      necessary to improve the in vivo imaging properties for plaque detection.

PMID- 12234588
TI  - Biodistribution study of [(123)I] ADAM in mice: correlation with whole body
      autoradiography.
AB  - Iodine-123 labeled 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine
      ([(123)I] ADAM) has been suggested as a promising serotonin transporter (SERT)
      imaging agent. Much research has been accomplished, mainly focusing on the SERT
      binding sites in the central nervous system (CNS). However, the biodistribution
      of [(123)I] ADAM using whole body autoradiography (WBAR) has never been
      previously described, to the best of our knowledge. In this study, we assayed the
      biodistribution of [(123)I] ADAM in tissues/organs removed from mice, and
      measured their radioactivity with a scintillation counter (SC). The results
      showed that the liver has the highest uptake. On the other hand, the WBAR clearly
      demonstrated that [(123)I] ADAM was bound to SERT-rich sites including those in
      the brain stem, lung, adrenal glands and intestinal mucosa. This radiotracer also
      accumulated in the liver, kidney, and thyroid. The results from both methods were
      compared; each has its own complementary role in the biodistribution studies. The
      SC method revealed the total amount of radiotracer accumulation in each organ,
      and the WBAR demonstrated more anatomical details of the radiotracer's
      distribution. The whole body distribution results of the radioligand using both
      methods explore the usage of this novel radioligand for most possible SERT
      binding sites, not only in the CNS but also in the peripheral nervous system and
      neuroendocrine tissues. These findings suggest that [(123)I] ADAM is a
      potentially useful imaging agent for SERT.

PMID- 12234590
TI  - Synthesis and evaluation of (11)C-labeled (S)-N-[[1-(2-phenylethyl) pyrrolidin-2
      yl]methyl]-3-methylthiobenzamide as a PET 5-HT(1A) receptor ligand.
AB  - We prepared 5-HT(1A) receptor ligands (S)-N-[[1-(2-phenylethyl)pyrrolidin-2
      yl]methyl]-3-[11C]methylthiobenzamide ([11C](S)-PPMMB) (Ki = 4.3 nM) and the less
      active [(11)C](R)-PPMMB (Ki = 160 nM) by reduction of the disulfide dimer and
      subsequent [(11)C]methylation of demethyl (S)- and (R)-PPMMB, respectively. Both
      radioligands showed similar brain distribution in mice with relatively higher
      affinity for the hippocampus being rich in 5-HT(1A) receptors than for other
      brain regions. Uptake of [(11)C](S)-PPMMB was not reduced by carrier-loading nor
      by pretreatment with 5-HT(1A) receptor ligands. [(11)C](S)-PPMMB is therefore not
      a suitable radioligand for mapping 5-HT(1A) receptors using positron emission
      tomography.

PMID- 12234589
TI  - PET examination of [(11)C]5-methyl-6-nitroquipazine, a radioligand for
      visualization of the serotonin transporter.
AB  - Radiohalogenated 5-halo-6-nitroquipazine analogues have been shown to be
      potential radioligands for visualization of the serotonin transporter (5-HTT)
      with PET and SPECT. In the present study a methylated analogue, 5-methyl-6
      nitroquipazine (MNQP), was radiolabeled with carbon-11 in a two step reaction via
      a palladium catalyzed cross coupling reaction between N-t-BOC-protected 5
      tributylstannyl-6-nitroquipazine and [(11)C]methyl iodide as key step.
      [(11)C]MNQP was examined in the cynomolgus monkey brain with positron emission
      tomography (PET) and the appearance of labeled metabolites in monkey plasma was
      measured with gradient HPLC. Radioactivity increased continuously in all brain
      regions during the 90 minutes acquisition time. Highest accumulation of
      radioactivity was observed in the thalamus and brainstem, regions with a known
      high density of 5-HTT. The calculated ratios between the thalamus and brainstem
      to the 5-HTT poor cerebellum were 1.5 and 1.3-1.4, respectively, 80 minutes after
      radioligand injection. Pretreatment with citalopram prior to the PET measurement
      markedly reduced the binding in the thalamus and the brainstem. At 15 and 30
      minutes after injection of [(11)C]MNQP approximately 90% and 60%, respectively,
      of radioactivity in plasma represented unchanged radioligand. The slow kinetics
      and moderate ratios recorded however, may limit its use as a PET radioligand for
      quantitative studies of the serotonin transporter with PET.

PMID- 12234591
TI  - Synthesis and biodistribution of a new (99m)Tc nitrido complex for cerebral
      imaging.
AB  - The bis(N-isopentyl dithiocarbamato) nitrido technetium-99m complex
      [(99m)TcN(IPEDTC)(2)] (IPEDTC: N-isopentyl dithiocarbamato) has been synthesized
      by the reduction of (99m)TcO(4)(-) into [(99m)TcN](2+) with stannous chloride in
      the presence of succinic dihydrazide and propylenediamine tetraacetic acid,
      followed by the addition of the sodium salt of N-isopentyl dithiocarbamate. The
      radiochemical purity of the complex was over 90% as measured by thin layer
      chromatography. In vitro studies showed that the complex possessed good stability
      under physiological conditions. Its partition coefficient indicated that it was a
      lipophilic complex. The electrophoresis results showed the complex was neutral.
      Biodistribution in mice showed that the complex accumulated in brain with high
      uptake and good retention. The brain uptake (ID%/g) was 2.22, 2.06 and 2.45 and
      the brain/blood ratio was 1.01, 2.34 and 3.22 at 5, 30 and 60 min post-injection,
      respectively. These results for the complex suggested that it could be a
      potential brain perfusion imaging agent.

PMID- 12234592
TI  - Carbon-11 labeled radioligands for imaging brain cannabinoid receptors.
AB  - Two radioligands, [(11)C] SR149080 and its morpholino analog [(11)C] SR149568,
      were synthesized by reaction of the respective phenolic precursors with [(11)C]
      methyl iodide. Both radioligands had appropriate regional brain distribution for
      cannabinoid receptors in mice with peak target to non-target ratios of 2.2 for
      [(11)C] SR149080 and 1.6 for [(11)C] SR149568 at 90 and 30 minutes post-injection
      respectively. The uptake of both tracers was blocked with a 1 mg/kg dose of
      SR141716A.

PMID- 12234593
TI  - Age-related changes of myocardial norepinephrine transporter density in rats:
      implications for differential cardiac accumulation of MIBG in aging.
AB  - The myocardial regional distribution of [(125)I]MIBG was examined in various aged
      (7-, 18-, 42-, 47-, and 65-week-old) rats and compared with the effects of
      regional myocardial blood flow and norepinephrine transporter (NET) function on
      regional [(125)I]MIBG accumulation in aged rats. In 7- and 18-week-old rats, the
      accumulation of [(125)I]MIBG was higher in the inferior wall than anterior wall.
      However, in more than 42-week-old rats, the uptake of MIBG was lower in the
      inferior wall than that the anterior wall. The uptake of [(99m)Tc]MIBI was
      greater in the inferior wall than the anterior wall in 18-week-old rats, but was
      reduced in the inferior wall compared to the anterior wall in 42- and 47- week
      old rats. Furthermore, the in vitro binding studies of [(3)H]desipramine to
      cardiac membranes showed that the B(max) value of NET was larger for the inferior
      wall than the anterior wall in 7-week-old rats, but was smaller for the inferior
      wall than the anterior wall in 47-week-old rats. The K(D) values for both walls
      were significantly larger in 47-week-old than 7-week-old rats. These results
      indicated that myocardial MIBG accumulation was lower in the inferior wall than
      the anterior wall of older rats, and that this differential MIBG accumulation in
      aging was related to the regional changes in myocardial blood flow and NET
      functions in the inferior wall.

PMID- 12234594
TI  - Transport of cis- and trans-4-[(18)F]fluoro-L-proline in F98 glioma cells.
AB  - The transport mechanisms of cis-4-[(18)F]fluoro-L-proline (cis-FPro) and trans-4
      [(18)F]fluoro-L-proline (trans-FPro) were studied in F98 rat glioma cells in
      comparison to the natural parent [(3)H]-L-proline. Uptake rates of cis-FPro and
      trans-FPro in F98 glioma cells were 50-70% lower than those of [(3)H]-L-proline.
      The amino transport system A inhibitor MeAIB reduced the uptake of [(3)H]-L
      proline by 30% and uptake of cis-FPro by 46% while uptake of trans-FPro was not
      significantly changed. BCH inhibited the uptake of all tracers by 35-44%, serine
      by 70-90% and L-proline by 60 -80%. Absence of Na(+) reduced uptake of all
      tracers significantly but no further inhibitory effect could be observed which
      suggests a component of unspecific uptake. Radioactivity of cis- and trans-FPro
      in the acid precipitable fraction was < 1% after 120 min incubation time while
      [(3)H]-L-proline exhibited a 20% incorporation into protein. Whole body PET scans
      in humans demonstrated a retention of cis-FPro in the renal cortex, liver and the
      pancreas while trans-FPro was retained particularly in muscles. We conclude that
      system A amino acid transport appears to be selectively relevant for cis-FPro
      which may contribute to the observed differences in whole body distribution of
      cis-FPro and trans-FPro in humans.

PMID- 12234595
TI  - Comparative antiproliferative effects of (111)In-DTPA-hEGF, chemotherapeutic
      agents and gamma-radiation on EGFR-positive breast cancer cells.
AB  - The antiproliferative effects of (111)In-DTPA-hEGF on breast cancer cells
      expressing high levels of EGFR were compared with those of chemotherapeutic
      agents or gamma-radiation. MDA-MB-468 cells were cultured with (111)In-DTPA-hEGF
      (30 MBq/microg, 1.8 x 10(5) MBq/micromol), DTPA-hEGF, methotrexate, doxorubicin,
      paclitaxel or 5-fluorouracil. Cell growth was measured colorimetrically. The
      IC(50) for 111In-DTPA-hEGF was < 70 pM (11 kBq/mL) versus 500 pM for DTPA-hEGF.
      The IC(50) for paclitaxel, methotrexate, doxorubicin and 5-fluorouracil was 6 nM,
      15 nM, 20 nM and 4 microM respectively. (111)In-DTPA-hEGF (70 pM, 11 kBq/mL)
      delivered approx. 6 Gy to breast cancer cells producing growth inhibition
      equivalent to 4 Gy of gamma-radiation. We conclude that (111)In-DTPA-hEGF
      exhibited potent antiproliferative effects towards breast cancer cells at
      concentrations much lower than chemotherapeutic agents and equivalent to those
      produced by several Gy of high dose rate gamma-radiation.

PMID- 12234596
TI  - Production and purification of gallium-66 for preparation of tumor-targeting
      radiopharmaceuticals.
AB  - Gallium-66 (T(1/2) = 9.49 h) is an intermediate-lived radionuclide that has
      potential for positron emission tomography (PET) imaging of biological processes
      with intermediate to slow target tissue uptake. We have produced (66)Ga by the
      (66)Zn(p,n) (66)Ga nuclear reaction using a small biomedical cyclotron and have
      investigated methods for purifying (66)Ga that could be applied to the
      development of an automated processing system. Measured yields of (66)Ga were
      very high with a production yield of nearly 14 mCi/microA-h at 14.5 MeV
      bombardment energy, a value in excellent agreement with theoretical predictions
      based on literature cross sections for the (66)Zn(p,n) (66)Ga reaction. Gallium
      66 has been purified from irradiated zinc targets two ways, by cation-exchange
      chromatography and diisopropyl ether extraction. The concentrations of stable
      contaminants in (66)Ga following the two processing methods were determined, and
      it was found that iron and zinc were present at levels up to an order of
      magnitude higher after cation-exchange chromatography. The bioconjugates DOTA
      Tyr(3)-octreotide and DOTA-biotin were labeled with (66)Ga purified by both
      methods. Following purification of (66)Ga by solvent extraction, radiochemical
      yields in excess of 85% were obtained for both compounds, in contrast to much
      lower labeling yields (less than 20%) obtained after the cation-exchange
      separation. Higher concentrations of stable contaminants likely contributed to
      the poor radiochemical yields for labeling DOTA-Tyr(3)-octreotide and DOTA-biotin
      with cation-exchanged (66)Ga. The lower purity and radiolabeling yields obtained
      using cation-exchange do not warrant the development of an automated processing
      system based on this method. Therefore, work is in progress to automate the
      diisopropyl ether extraction method for routine processing of (66)Ga.

PMID- 12234597
TI  - Preparation of (99m)Tc-C(60)(OH)(x) and its biodistribution studies.
AB  - The biological behavior of fullerene derivatives shows their considerable
      potential for medical applications. In order to provide a C(60) derivative for
      biodistriburtion studies, the (99m)Tc-labeling of C(60)(OH)(x) was optimized.
      Gamma counting and single photon emission computed tomography (SPECT) were used
      to assess the biodistribution of the (99m)Tc-labeled compound in mice and
      rabbits. Biodistribution studies in mice and imaging of rabbits indicated that
      (99m)Tc-C(60)(OH)(x) was widely distributed in all tissues. A significant
      percentage of total activity was retained for 48 h, particularly in the kidneys,
      bone, spleen, and liver. All tissues displayed a slow clearance over 48 h, except
      for bone, which showed slightly increasing localization within 24 h.

PMID- 12234598
TI  - Cationic complex: (99m)Tc-N,N'-dimethyldiaminedithiol.
AB  - Diaminedithiol (DADT) or N-monosubstituted DADT is known to form lipophilic
      neutral chelates with technetium. As a result, they are used for brain imaging
      agents. However, 99mTc-N,N'-dimethylDADT has been demonstrated to have a positive
      charge and a lower lipophilicity (log P = 0.1) in this experiment. The results of
      a biodistribution study showed that most activity was found in the intestine
      after 1 hr, which is the evidence of bile excretion. Increased heart-uptake in
      mice suggests that this compound or its derivatives can be used as a myocardial
      imaging agent.

PMID- 12234599
TI  - Glutamate antagonists limit tumor growth.
AB  - The management of malignancies in humans constitutes a major challenge for
      contemporary medicine. Despite progress in chemotherapy, bone marrow
      transplantation, surgical measures, and radiation technologies, and in
      immunological and immunomodulatory approaches, humans continue to succumb to
      cancer due to tumor recurrence and metastatic disease. The excitatory
      neurotransmitter glutamate, which regulates proliferation and migration of
      neuronal progenitors and immature neurons during the development of the mammalian
      nervous system, is present in peripheral cancers. Since both neuronal progenitors
      and tumor cells possess propensity to proliferate and to migrate, and since
      glutamate and glutamate receptors are known to modify these phenomena in the
      nervous system, we proceeded to investigate the possible influence of glutamate
      antagonists on the proliferation and migration of tumor cells. We found and
      recently reported that glutamate N-methyl-D-aspartate (NMDA) and alpha-amino-3
      hydroxy-5-methyl-4-isoxazole-propionate (AMPA) antagonists inhibit the
      proliferation of human colon adenocarcinoma, astrocytoma, breast and lung
      carcinoma, and neuroblastoma cells in vitro. The antiproliferative effect of
      glutamate antagonists is Ca(2+)-dependent and results from decreased cell
      division and increased cell death. Glutamate antagonists produce morphological
      alterations in tumor cells, which consist of reduced membrane ruffling and
      pseudopodial protrusions, and decrease their motility and invasive growth.
      Furthermore, glutamate antagonists enhance in vitro cytostatic and cytotoxic
      effects of common chemotherapeutic agents used in cancer therapy. These findings
      demonstrate the anticancer potential of glutamate antagonists and suggest that
      they may be used as an adjunctive measure in the treatment of cancer.

PMID- 12234600
TI  - Characterization of the cAMP binding site of purified S-adenosyl-homocysteine
      hydrolase from bovine kidney.
AB  - The enzyme S-adenosyl-homocysteine hydrolase (AdoHcyase) which catalyzes the
      reversible hydrolysis of AdoHcy to adenosine and homocysteine is an adenosine
      binding protein. In the present study we examined the characteristics of
      [(3)H]cAMP binding to purified AdoHcyase from bovine kidney in comparison with
      the high affinity adenosine binding site of AdoHcyase. AdoHcyase exhibits one
      [(3)H]cAMP binding site with an affinity of K(d)=23.1+/-1.1nM and a B(max) of
      116.6+/-3.8pmol/mg protein. Binding of [(3)H]cAMP obeyed a monophasic reaction
      with a k(+1) value of 0.035min/M. The dissociation of AdoHcyase-[(3)H]cAMP
      complex exhibited a time- and temperature-dependent character. After a 240min
      incubation at 0 degrees only 5-10%, however, at 20 degrees 90% were displaceable.
      Adenosine and cAMP displace each other with similar affinities of EC(50) 57nM vs.
      EC(50) 65nM. 2'-Deoxyadenosine, N(6)-methyladenosine, and NECA displace 25nM
      [(3)H]cAMP and 10nM [(3)H]adenosine with EC(50) values of 94, 90 and 80nM,
      respectively. All other nucleosides studied, adenine, inosine, adenosine-2',3'
      dialdehyde, 2-chloroadenosine, aristeromycin, and adenine nucleotides were only
      week competitors for [(3)H]cAMP and [(3)H]adenosine. These compounds displace
      [(3)H]cAMP and [(3)H]adenosine with equal potencies. Our data indicate that the
      binding site for nanomolar concentrations of cAMP and adenosine at the AdoHcyase
      appears to be identical. The physiological implications of a cAMP binding site at
      the AdoHcyase remain to be established.

PMID- 12234601
TI  - Antagonist interaction with endogenous AT(1) receptors in human cell lines.
AB  - Using Chinese Hamster Ovary cells expressing human AT(1) receptors cells (CHO
      hAT(1)), it was previously shown that insurmountable inhibition of the
      angiotensin II response by non-peptide antagonists is related to the duration of
      their receptor occupancy. In the present study it was shown that these
      antagonists displayed similar binding characteristics to endogenously expressed
      AT(1) receptors in human adrenal cortex cells (NCI-h295) and renal vascular
      smooth muscle cells (HVSMC). Competition binding studies with [(3)H]candesartan
      for NCI-h295 cells, with [(125)I]Sar(1)-Ile(8) angiotensin II for HVSMC and with
      both radioligands for CHO-hAT(1) cells displayed the same potency order for
      unlabelled antagonists: candesartan>EXP3174>irbesartan>losartan. The AT(2)
      receptor antagonist PD123319 displayed low potency in all instances. The apparent
      half-lives of the antagonist-AT(1) receptor complexes in NCI-h295 cells and HVSMC
      were comparable to those obtained under identical conditions with CHO-hAT(1)
      cells. Angiotensin II increased the inositol phosphate accumulation dose
      dependently with half-maximal response at 17.4+/-1.6nM for NCI-h295 cells and
      4.5+/-0.8nM for HVSMC. Pre-incubation of the cells with losartan only produced
      concentration-dependent rightward shifts of the angiotensin II concentration
      response curve. The maximal response was decreased by 85-92% with candesartan, 70
      88% with EXP3174 and 60% with irbesartan. The similar binding and inhibitory
      properties of these antagonists among the investigated cell types validates the
      use of CHO-hAT(1) cells for investigating pharmacological properties of human
      AT(1) receptors.

PMID- 12234602
TI  - Contribution of apoptosis in the cytotoxicity of the oxaliplatin-irinotecan
      combination in the HT29 human colon adenocarcinoma cell line.
AB  - Interactions between the topoisomerase I inhibitor irinotecan (CPT-11) and the
      platinum derivative oxaliplatin (L-OHP) were investigated in HT29 colon cancer
      cell line. Synergism was observed when cells were simultaneously exposed to drugs
      or when cells were first exposed to CPT-11. Flow cytometric studies showed a
      G(2)/M accumulation when cells were exposed to the simultaneous and CPT-11-->L
      OHP combinations whereas a persistent S phase delay was observed when cells were
      first exposed to L-OHP. We characterised the cytotoxic effect by assessing the
      induction of apoptosis. Irinotecan induced substantial DEVDase activity and
      poly(ADP-ribose) polymerase cleavage while this activity was moderate and delayed
      after exposure to L-OHP. Combination experiments showed a sequence-dependent
      onset of apoptosis, the CPT-11-->L-OHP schedule being the earliest and the most
      effective; on the other hand the apoptotic signaling generated by CPT-11 was
      partly inhibited in the simultaneous combination and in the L-OHP-->CPT-11
      sequence. Cell death studies using a dual staining technique showed a shift from
      apoptosis to necrosis when combining these drugs at high concentrations.
      Synergistic interactions observed using CPT-11 before L-OHP may be linked to an
      early apoptotic signaling while the L-OHP-induced S phase block could account for
      the observed additive effect in the reverse sequence. An additional phenomenon
      might work towards synergism for the simultaneous combination.

PMID- 12234603
TI  - Diverse functional coupling of cyclooxygenase 1 and 2 with final prostanoid
      synthases in liver macrophages.
AB  - Lipopolysaccharide (LPS) treatment of resident liver macrophages resulted in a
      coordinated enhanced expression of cytosolic phospholipase A(2) (cPLA(2)),
      cyclooxygenase (COX)-2 and prostaglandin E(2)-synthase. LPS-pretreated liver
      macrophages showed a higher release of PGE(2) after zymosan, phorbol ester and
      A23187, of PGF(2alpha) after zymosan and A23187, whereas the release of
      thromboxane B(2) and PGD(2) was unchanged. Inhibition of COX-1 and -2 by specific
      inhibitors (SC560, SC236) inhibited the prostanoid release between 50-80% and 20
      40%, respectively, indicating a predominant role for COX-1. In detail (1) the
      zymosan-induced release of all prostanoids was inhibited to a similar degree by
      the COX-1 inhibitor (about 70%) and the COX-2 inhibitor (20-30%), (2) PGE(2)
      release after all stimuli was inhibited to a greater extent by SC560 (70-90%)
      compared to SC236 (5-30%), (3) the phorbol ester- and A23187-induced release of
      PGF(2alpha) and PGD(2) was inhibited equally (40-50%) by both inhibitors, (3)
      TxB(2) release after phorbol ester and A23187 was inhibited by SC560 by 50 and
      30%, and by SC236 by 50 and 70%, respectively. cPLA(2), COX-1 and -2, and the
      final prostanoid synthases were found in different subcellular fractions. These
      results indicate, that the functional coupling of COX-1 and -2 to final
      prostanoid synthases depends on the stimulation of the cells.

PMID- 12234604
TI  - Potentiation of 1,25-dihydroxyvitamin D(3)-induced differentiation of human
      promyelocytic leukemia cells into monocytes by costunolide, a germacranolide
      sesquiterpene lactone.
AB  - Costunolide, a germacranolide sesquiterpene lactone that exists in several
      medicinal plants, is known to be a possible anti-cancer and chemopreventive agent
      for tumorigenesis. In this report, we investigated the effect of costunolide on
      cellular differentiation in the human promyelocytic leukemia HL-60 cell culture
      system. Costunolide markedly increased the degree of HL-60 leukemia cell
      differentiation when simultaneously combined with 5nM 1,25-dihydroxyvitamin D(3)
      (1,25-(OH)(2)D(3)). Costunolide by itself had very weak effects on the
      differentiation of HL-60 cells. Cytofluorometric analysis and cell morphologic
      studies indicated that costunolide potentiated 1,25-(OH)(2)D(3)-induced cell
      differentiation predominantly into monocytes. Inhibitors for PKC, PI3-K, and ERK
      markedly inhibited HL-60 cell differentiation induced by costunolide in
      combination with 1,25-(OH)(2)D(3). In addition, pretreatment of HL-60 cells with
      costunolide before the 1,25-(OH)(2)D(3) addition also potentiated cell
      differentiation in a concentration- and time-dependent manner, and the enhanced
      levels of cell differentiation closely correlated with the inhibitory levels of
      NF-kappaB-binding activity by costunolide. These results indicate that PKC, PI3
      K, ERK and NF-kappaB may be involved in 1,25-(OH)(2)D(3)-mediated cell
      differentiation enhanced by costunolide.

PMID- 12234605
TI  - Comparative analysis of human and rat S1P(5) (edg8): differential expression
      profiles and sensitivities to antagonists.
AB  - Five guanine nucleotide-binding protein-coupled receptors (S1P(1-5)) for the
      lysophospholipid mediator sphingosine 1-phosphate (S1P) have thus far been
      described. Whereas tissue distribution and functional properties of the human
      S1P(1-4) genes are well characterized, only limited functional and expression
      data are available for S1P(5), todate. Northern blot analysis indicated that
      human S1P(5) (hS1P(5)) is an alternatively spliced gene, with a 5.4-kb transcript
      that is predominantly expressed in peripheral tissues, and a 2.4-kb transcript
      expressed in brain, spleen, and peripheral blood leucocytes. In contrast, rat
      S1P(5) (rS1P(5)) was exclusively detected in brain and skin. Expression of
      hS1P(5) and rS1P(5) in mammalian CHO-K1 or HEK293 cells conferred onto the cells
      the ability to mobilize intracellular calcium as determined by a functional
      Fluorometric Imaging Plate Reader assay, when challenged with S1P and dihydro
      S1P, respectively. Applying a lipid library with 200 bioactive lipids in a
      functional Fluorometric Imaging Plate Reader assay did not reveal additional
      agonists. However, both receptors exhibited differential sensitivity towards the
      S1P- and lysophosphatidic acid-receptor antagonist, suramin: rS1P(5)-mediated
      intracellular calcium mobilization was partly inhibited by suramin (IC(50): 5800
      microM), whereas hS1P(5) was completely antagonized (IC(50): 130 microM). Both
      receptors were sensitive towards inhibition with the related drug (8,8'
      (carbonylbis(imino-3,1-phenylene))bis(1,3,5-naphthalenetrisulfonic acid)) but
      IC(50) values differed significantly (340 microM for hS1P(5), 4000 microM for
      rS1P(5)). In addition, rS1P(5) displayed antiproliferative effects in transfected
      CHO-K1 and HEK293 cells in contrast to hS1P(5). Taken together, our data imply
      that differences between hS1P(5) and rS1P(5) will be an important point to be
      considered in the development of selective receptor antagonists.

PMID- 12234606
TI  - Modulation of agonist responses at the A(1) adenosine receptor by an irreversible
      antagonist, receptor-G protein uncoupling and by the G protein activation state.
AB  - Potency and intrinsic activity of agonists depend on ligand structure, but are
      also regulated by receptor-G protein stoichiometry. A potential functional
      reserve in adenosine A(1) receptor-mediated G protein activation was investigated
      by stimulation of guanosine-5'-(gamma-[35S]thio)-triphosphate ([35S]GTPgammaS)
      binding by the full agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) and the
      partial agonist 5'-deoxy-5'-methylthioadenosine (MeSA). Pretreatment of rat brain
      membranes with the irreversible antagonist 1-propyl-3-[3-[[4
      (fluorosulfonyl)benzoyl]oxy]-propyl]-8-cyclopentylxanthine revealed no classical
      receptor reserve for either agonist. The functional significance of the G protein
      coupling state of the receptor and occupancy of G proteins by guanine nucleotides
      was assessed after partial uncoupling of receptor-G protein complexes with N
      ethylmaleimide and in the presence of increasing GDP concentrations. Agonist
      EC(50) values in G protein activation were increased after NEM pretreatment and
      at higher GDP concentrations, and a decrease in the relative intrinsic activity
      of MeSA was observed. The shift of agonist concentration-response curves to the
      right, the decrease in maximal effects and the decrease in relative intrinsic
      activity of the partial agonist point to a functional reserve which has to be
      attributed to GDP-free receptor-G protein complexes. The mechanisms of action of
      FSCPX, NEM and GDP were fully consistent with the two-state model of receptor
      activation. The apparent reserve revealed by GDP reflects a shift from
      spontaneously active GDP-free receptor-G protein complexes (RG)(*), which can
      bind [35S]GTPgammaS, to (RG) occupied by GDP. The abundance of (RG)(*) is favored
      by agonists and by the absence of GDP.

PMID- 12234607
TI  - The activity profile of the hexacyclic camptothecin derivative DX-8951f in
      experimental human colon cancer and ovarian cancer.
AB  - DX-8951f or exatecan mesylate ((1S,9S)-1-amino-9-ethyl-5-fluoro-2,3-dihydro-9
      hydroxy-4-methyl-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10
      13(9H,15H)-dione methanesulfonate dihydrate), is a new water-soluble derivative
      of camptothecin. We determined the activity of DX-8951f in experimental human
      colon cancer and ovarian cancer, being tumor types sensitive to camptothecins.
      With the use of the MTT assay, DX-8951f was more potent than SN-38 in four out of
      five human colon cancer cell lines and three out of four human ovarian cancer
      cell lines (P<0.05). DX-8951f was considerably more potent than topotecan in all
      cell lines tested (P<0.05). Prolonged exposure to DX-8951f resulted in a greater
      increase in inhibition of cell proliferation as compared to that obtained with SN
      38 or topotecan (P<0.05). Overexpression of Pgp, MRP1, and LRP did not affect the
      in vitro activity of DX-8951f. DX-8951f administered daily x 5 or weekly x 2
      resulted in growth inhibition <50% in two human colon cancer xenografts grown
      s.c. in nude mice. In three human ovarian cancer xenografts, however, >50% growth
      inhibition was observed at both schedules. In the OVCAR-3 human ovarian cancer
      model, DX-8951f showed considerably greater activity than topotecan (P<0.01). DX
      8951f combined with cisplatin or paclitaxel did not indicate the presence of a
      pharmacological interaction. In OVCAR-3 xenografts the combination was clearly
      more effective than DX-8951f alone, as the number of complete remissions
      increased substantially. In conclusion, this study shows that DX-8951f is highly
      potent in vitro and highly effective in experimental human ovarian cancer in
      vivo. Prolonged exposure to DX-8951f in vitro greatly increased the
      antiproliferative effects, which may be a rationale for testing a continuous
      infusion schedule in the clinic. Addition of cisplatin or paclitaxel improved the
      in vivo antitumor effects of DX-8951f.

PMID- 12234608
TI  - Novel competitive irreversible inhibitors of aldehyde dehydrogenase (ALDH1):
      restoration of chemosensitivity of L1210 cells overexpressing ALDH1 and induction
      of apoptosis in BAF(3) cells overexpressing bcl(2).
AB  - 4-Amino-4-methyl-pent-2-ynthioc acid S-methyl ester (ampal thiolester: ATE) was
      used as a lead compound to synthesise new amino-substituted derivatives of alpha,
      beta acetylenic thiolester compounds as inhibitors of aldehyde dehydrogenase 1,
      (ALDH1). Of these compounds, the dimethyl derivative (DIMATE) was a competitive
      irreversible inhibitor (K(i) approximately 280 microM) of baker's yeast ALDH1 in
      vitro showing 80% inhibition at 400 microM when preincubated with the enzyme for
      30min, whereas the trimethyl ammonium and the morpholine derivatives showed only
      15% inhibition at 600 microM even after 60min preincubation. ATE inhibited ALDH1
      activity in ALDH1-transfected L1210 T cells resistant to
      hydroperoxycyclophosphamide (HCPA) and inhibited growth synergistically in the
      presence of HCPA. In non-transfected L1210 counterparts ATE did not potentiate
      growth inhibition by HCPA. DIMATE was a 30-100-fold more effective growth
      inhibitor than ATE. Endogenous ALDH1 activities of BAF(3) cells over-expressing
      different levels of bcl(2) (0-100%) were similar (16-20mU/mg protein) and were
      all inhibited by DIMATE, reaching 20-30% at 4 microM. Up to 4 microM no
      apoptosis, as measured by DNA-fragmentation was observed, but at 8 and 10 microM
      DIMATE, DNA-fragmentation increased concomitantly with ALDH1 inhibition. No DNA
      fragmentation was observed with ALDH1 irreversible inhibitors devoid of a
      thiolester group or with thiolesters which were not inhibitors of ALDH1. It was
      seen only with competitive irreversible inhibitors having the methanethiol and
      enzyme-inhibitory moieties. The methanethiol putatively released from DIMATE by
      ALDH1 esterase activity plays a role, albeit undefined, in lowering
      intramitochondrial glutathione levels which decreased by 47% as DNA-fragmentation
      increased.

PMID- 12234609
TI  - Degradation of nociceptin (orphanin FQ) by mouse spinal cord synaptic membranes
      is triggered by endopeptidase-24.11: an in vitro and in vivo study.
AB  - We analyzed spinal metabolic pathway of nociceptin/orphanin FQ related to pain
      transmission or modulation in the both in vitro and in vivo experiments.
      Nociceptin was degraded by spinal synaptic membranes. Major metabolites of
      nociceptin were free phenylalanine, nociceptin (1-13) and nociceptin (14-17).
      Both the degradation of nociceptin and the accumulation of the major cleavage
      metabolites, nociceptin (1-13) and nociceptin (14-17), were strongly inhibited by
      a metal chelator and also by specific inhibitors of endopeptidase-24.11,
      thiorphan and phosphoramidon. Furthermore, purified endopeptidase-24.11
      hydrolyzed nociceptin at the cleavage site (Lys(13)-Leu(14) bond) identical to
      that by spinal synaptic membranes. Recently, we have found that nociceptin,
      injected intrathecally at small doses (fmol order) elicits a behavioral response
      consisting of scratching, biting and licking in mice. In the present study, we
      have examined the effect of peptidase inhibitors on the behavioral response
      elicited by intrathecal injection of nociceptin in mice. Phosphoramidon
      simultaneously injected with nociceptin additively enhanced nociceptin-induced
      behavioral response, whereas the nociceptin-induced behavioral response was
      unaffected by either bestatin, an aminopeptidase inhibitor or captopril, an
      angiotensin-converting enzyme inhibitor. However, the nociceptin effect was
      potentiated by combined injection of phosphoramidon and bestatin, indicating that
      inhibition of aminopeptidase may also contribute to inducing the behavioral
      response to nociceptin. These data suggest that endopeptidase-24.11 plays a major
      role in initial stage of nociceptin metabolism at the spinal cord level in mice.

PMID- 12234610
TI  - A novel pathway regulating the mammalian target of rapamycin (mTOR) signaling.
AB  - Originally discovered as an anti-fungal agent, the bacterial macrolide rapamycin
      is a potent immunosuppressant and a promising anti-cancer drug. In complex with
      its cellular receptor, the FK506-binding protein (FKBP12), rapamycin binds and
      inhibits the function of the mammalian target of rapamycin (mTOR). By mediating
      amino acid sufficiency, mTOR governs signaling to translational regulation and
      other cellular functions by converging with the phosphatidylinositol 3-kinase
      (PI3K) pathway on downstream effectors. Whether mTOR receives mitogenic signals
      in addition to nutrient-sensing has been an unresolved issue, and the mechanism
      of action of rapamycin remained unknown. Our recent findings have revealed a
      novel link between mitogenic signals and mTOR via the lipid second messenger
      phosphatidic acid (PA), and suggested a role for mTOR in the integration of
      nutrient and mitogen signals. A molecular mechanism for rapamycin inhibition of
      mTOR signaling is proposed, in which a putative interaction between PA and mTOR
      is abolished by rapamycin binding. Collective evidence further implicates the
      regulation of the rapamycin-sensitive signaling circuitry by phospholipase D, and
      potentially by other upstream regulators such as the conventional protein kinase
      C, the Rho and ARF families of small G proteins, and calcium ions. As the mTOR
      pathway has been demonstrated to be an important anti-cancer target, the
      identification of new components and novel regulatory modes in mTOR signaling
      will facilitate the future development of diagnostic and therapeutic strategies.

PMID- 12234611
TI  - Effects of FK228, a novel histone deacetylase inhibitor, on human lymphoma U-937
      cells in vitro and in vivo.
AB  - FK228 [(E)-(1S,4S,10S,21R)-7-[(Z)-ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia
      5,8,20,23-tetraazabicyclo-[8,7,6]-tricos-16-ene-3,6,9,19,22-pentanone; FR901228,
      depsipeptide] is a novel histone deacetylase inhibitor that shows therapeutic
      efficacy in Phase I trials of patients with malignant lymphoma. However, its
      mechanism of action has not been characterized. In this study, we examined the in
      vitro and in vivo effects of FK228 on human lymphoma U-937 cells. FK228 very
      strongly inhibited the growth of U-937 cells with an IC(50) value of 5.92 nM. In
      a scid mouse lymphoma model, mice treated with FK228 once or twice a week
      survived longer than control mice, with median survival times of 30.5 (0.56
      mg/kg) and 33 days (0.32 mg/kg), respectively (vs. 20 days in control mice).
      Remarkably, 2 out of 12 mice treated with FK228 (0.56 mg/kg once or twice a week)
      survived past the observation period of 60 days. The apoptotic population of U
      937 cells time-dependently increased to 37.7% after 48 hr of treatment with
      FK228. In addition, FK228 induced G1 and G2/M arrest and the differentiation of U
      937 cells to the CD11b(+)/CD14(+) phenotype. Expression of p21(WAF1/Cip1) and
      gelsolin mRNA increased up to 654- and 152-fold, respectively, after 24hr of
      treatment with FK228. FK228 caused histone acetylation in p21(WAF1/Cip1) promoter
      regions, including the Sp1-binding sites. In conclusion, (i) FK228 prolonged the
      survival time of scid mice in a lymphoma model, and (ii) the beneficial effects
      of FK228 on human lymphoma may be exerted through the induction of apoptosis,
      cell cycle arrest, and differentiation via the modulation of gene expression by
      histone acetylation.

PMID- 12234612
TI  - SU9516, a cyclin-dependent kinase 2 inhibitor, promotes accumulation of high
      molecular weight E2F complexes in human colon carcinoma cells.
AB  - The E2F family plays a critical role in the expression of genes required for
      entry into and progression through S phase. E2F-mediated transcription is
      repressed by the tumor suppressor retinoblastoma protein (pRb), which results in
      sequestration of E2F in a multiprotein complex that includes pRb. Derepression of
      E2F results from a series of complex phosphorylation events mediated by cyclin
      D/cdk4 and cyclin E/cdk2. We have employed a novel 3-substituted indolinone
      compound, 3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2
      one (SU9516), which selectively inhibits cdk2 activity (Lane et al., Cancer Res
      2001;61:6170-7) to investigate these events. Electrophoretic mobility gel shift
      assays were performed on SU9516-treated and -untreated HT-29, SW480, and RKO
      human colon cancer cell extracts. Treatment with 5 microM SU9516 prevented
      dissociation of pRb from E2F1 in all cell lines (HT-29>RKO>SW480). Treatment
      effects were time-dependent, demonstrating greater inhibition at 48 hr versus
      24hr in HT-29 cells. Furthermore, E2F species were sequestered in complexes with
      p107, p130, DP-1, and cyclins A and E. After a 24-hr treatment with 5 microM
      SU9516, cyclin D1 and cdk2 levels decreased by 10-60%. These findings delineate a
      previously undescribed mechanism for SU9516-mediated cell growth arrest through
      down-regulation of cyclin D1, inhibition of cdk2 levels and activity, and pan
      sequestration of E2F.

PMID- 12234613
TI  - Complementary DNA cloning and characterization of cytochrome P450 2D29 from
      Japanese monkey liver.
AB  - A cDNA was cloned from Japanese monkey liver mRNA by reverse transcriptase
      polymerase chain reaction (RT-PCR) using oligonucleotide primers based on the
      marmoset cytochrome P450 2D19 (CYP2D19) nucleotide sequence. The full-length cDNA
      encoded a 497 amino acid protein (designated CYP2D29) that is 96, 91, and 88%
      homologous to human CYP2D6, cynomolgus monkey CYP2D17, and marmoset monkey
      CYP2D19, respectively. Yeast cells (Saccharomyces cerevisiae AH-22 strain)
      transfected with pGYR1 vectors containing the CYP2D29 cDNA were cultured, and
      microsomal fractions were obtained. Reduced carbon monoxide-difference spectra
      and western blot analysis using polyclonal antibodies raised against rat CYP2D2
      demonstrated that in yeast cell microsomal fractions, the level of CYP2D29
      holoenzyme was similar to that of CYP2D6 holoenzyme. However, western blot
      analysis indicated that the level of CYP2D29 in Japanese monkey liver microsomes
      might be much higher than that of CYP2D6 in human liver microsomes. Japanese
      monkey liver microsomes exhibited much higher activities than did human liver
      microsomes, expressed as nmol/min/mg protein, for debrisoquine (DB) 4
      hydroxylation and bufuralol (BF) 1"-hydroxylation (typical reactions catalyzed by
      CYP2D6), whereas recombinant CYP2D29 activity, expressed as nmol/min/nmol CYP,
      was similar to that of CYP2D6 for DB and BF hydroxylation. In kinetic analyses,
      the K(m) value of CYP2D29 for DB 4-hydroxylation was much lower than that of
      Japanese monkey liver microsomes, whereas the K(m) value of CYP2D6 for DB 4
      hydroxylation was similar to that of human liver microsomes. In contrast, K(m)
      values for BF 1"-hydroxylation were similar for Japanese monkey and human liver
      microsomes and yeast cell microsomal fractions expressing recombinant CYP2D29 or
      CYP2D6. These results suggest that the properties of Japanese monkey CYP2D29 are
      similar to those of human CYP2D6, but their populations and/or some other factors
      in liver microsomes may cause the difference in microsomal DB 4-hydroxylase
      activities between Japanese monkeys and humans.

PMID- 12234614
TI  - Chemosensitization by fibroblast growth factor-2 is not dependent upon
      proliferation, S-phase accumulation, or p53 status.
AB  - Fibroblast growth factor-2 (bFGF/FGF-2) is a pleiotropic growth factor that
      functions as a survival factor and directs apoptosis during embryogenesis and
      development. As a survival factor, FGF-2 would be expected to protect cells
      against drug toxicities. Such protection has been reported in some cells treated
      with some chemotherapeutic drugs. However, we recently demonstrated that FGF-2
      can sensitize NIH 3T3 mouse fibroblasts to the cytotoxic and apoptotic effects of
      cisplatin. Sensitization requires prolonged incubation of cells with FGF-2 before
      the addition of cisplatin, and it requires an FGF-2 concentration (5-10 ng/mL)
      that is higher than that needed for its mitogenic effects (0.5 ng/mL). We now
      report that FGF-2 can also sensitize MCF7 human breast cancer cells and A2780
      human ovarian cancer cells, as well as NIH 3T3 cells, to cisplatin. FGF-2 did not
      affect the cisplatin sensitivity of SKOV3 ovarian cancer cells or a panel of
      seven pancreatic cancer cell lines. We have demonstrated that the sensitizing
      effect is not simply a function of the mitogenic activity of FGF-2 on cells, as
      we did not observe sensitization with other growth-stimulatory factors (FGF-1 and
      epidermal growth factor); the sensitizing effect of FGF-2 was observed even with
      cell lines that were not growth-stimulated by FGF-2; and sensitization was not
      restricted to cells in S-phase of the cell cycle. These results indicate that
      cell proliferation is neither necessary nor sufficient for sensitization by FGF
      2. Moreover, sensitization to cisplatin appears to be p53-independent, as p53
      null 3T3 10-1 cells were equally sensitized by FGF-2. Finally, FGF-2 also
      sensitized NIH 3T3 and MCF7 cells to carboplatin, and had smaller effects on the
      sensitivity of these cell lines to doxorubicin and docetaxel. FGF-2 had no effect
      on sensitivity to etoposide in any cell line tested. Therefore, sensitization by
      FGF-2 was most effective with the platinum compounds, suggesting that this
      activity may be specific to particular mechanisms of drug action.

PMID- 12234615
TI  - Use of Chlamydomonas reinhardtii mutants for anticancer drug screening.
AB  - We investigated the possibility of utilizing alga cells instead of mammalian
      cells for the screening of anticancer drugs. The alga cells grow in synthetic
      media whereas the mammalian cells require complex and more expensive media along
      with heavy investment and manpower. To assess the validity of this new approach,
      analysis of growth inhibition by antitumor agents was carried out jointly on a
      wall-less (cw15) mutant of Chlamydomonas reinhardtii, that obviates the problem
      of drug uptake, and the murine leukemic cell line L1210, commonly used for
      anticancer drug screening. The presence of the topoisomerases I and II
      (approximately 97 and approximately 2 x 170 kDa, respectively) in the nuclear
      extracts of C. reinhardtii and their possible role as targets of the drugs was
      also investigated. Concentrated extracts were separated into >100 and <100 kDa
      fractions and their topoisomerase I and II activities were measured on relaxation
      of supercoiled plasmid DNA, decatenation of the catenated kinetoplast DNA and
      cleavage of plasmid DNA. Our results do not show significant difference in growth
      inhibition by antitumorals between the wall-less mutant of the alga and the
      murine leukemic cell line L1210. We noted that alga cells were inhibited by
      antibiotics that target gyrase, a bacterial variant of topoisomerase II which is
      also found in chloroplasts. At the molecular level, the alga nuclear fractions,
      >100 and <100 kDa, displayed the same activities as the mammalian enzymes
      topoisomerases I and II, respectively, and were blocked by the same poisons. We
      concluded that the wall-less cw15 mutant of C. reinhardtii could advantageously
      replace mammalian cells in the screening of the anticancer drugs. The alga
      enzymes could also provide an opportunity to delineate the phylogeny of the
      topoisomerase superfamily.

PMID- 12234616
TI  - Effects of nitrosopropofol on mitochondrial energy-converting system.
AB  - Nitrosopropofol (NOPR) is a relatively stable compound obtained from the reaction
      between the general anesthetic 2,6 diisopropylphenol (propofol) and
      nitrosoglutathione (GSNO) and bearing a more acidic phenol group than propofol.
      It interfered with mitochondrial energetic metabolism in a concentration
      dependent manner. Concentrations as high as 100 or 200 microM disrupted both
      oxidative phosphorylation and electron transport. Low concentrations of NOPR (50
      microM) markedly slowed down the electron transport rate which was insensitive
      both to ADP and uncoupler stimulation and spontaneously gradually stopped.
      Consequently, both the transmembrane potential production and the ATP synthesis
      system were affected. In the presence of 10 or 20 microM NOPR, mitochondria
      respired but showed a worsening of the respiratory control and produced a
      transmembrane potential useful to respond to a phosphorylation pulse, but were
      not able to restore it. These results were consistent with ATP synthesis and
      swelling experiments. NOPR was effective at concentrations lower than those
      required by the combination of propofol and GSNO, suggesting that mitochondria
      might be able to catalyze the reaction between GSNO and propofol and that the
      resulting metabolite was more active on mitochondrial membrane structure than the
      parent compounds. Although the details of the process are yet unknown, the
      mechanism presented may be of potential relevance to rationalize the
      pathophysiological effects of propofol.

PMID- 12234617
TI  - Effect of free iron on collagen synthesis, cell proliferation and MMP-2
      expression in rat hepatic stellate cells.
AB  - Various studies on hepatic fibrosis occurring in iron overload suggest that
      excess of tissue iron may be involved in the stimulation of collagen synthesis.
      Anyway, up to date, direct evidence on the role of iron in hepatic fibrosis is
      lacking. Moreover, it is not clear whether iron acts as direct initiator of
      fibrogenesis or as mediator of hepatocellular necrosis. In the present study, we
      investigated the effect of nontoxic doses of iron on collagen metabolism and
      proliferation, key features of liver fibrosis, by means of cultures of hepatic
      stellate cells, the liver cells responsible for collagen production. Iron
      treatment increased collagen synthesis without affecting noncollagen proteins.
      The maximum effect was observed at 5 microM iron (+132%). At this dose, no cell
      damage or proliferation was detected. Conversely, higher doses of iron (10 and 25
      microM) induced cell proliferation and a lower increase in collagen synthesis,
      suggesting the prevalence of proliferative effect on the synthetic one. These
      effects occurred without the intervention of serum factors and were not mediated
      by lipid peroxidation. Our results strongly support the hypothesis that iron "per
      se" may act as a profibrogenic agent. Finally, we provide evidence that iron
      plays a role also in matrix degradation, by stimulating some metalloprotease
      activities. Iron treatment increased metalloprotease-2 activity in hepatic
      stellate cells, while no changes were observed for interstitial collagenase
      activity suggesting that, in these conditions, a pathological accumulation of
      hepatic extracellular matrix may occur.

PMID- 12234618
TI  - Regulation of anandamide tissue levels by N-arachidonylglycine.
AB  - N-arachidonylglycine (NAGly), the carboxylic analog of the endocannabinoid
      anandamide, occurs in rat and bovine brain as well as in peripheral sites and
      shows activity against tonic, formalin-induced pain. It was also observed, using
      cell membrane preparations, that it inhibits the hydrolytic activity of fatty
      acid amide hydrolase (FAAH) on anandamide (N-arachidonylethanolamide). These data
      suggested that it may serve as an endogenous regulator of tissue anandamide
      concentrations. In this report, we show findings derived from mass spectrometric
      analyses, indicating that blood levels of anandamide in rats given 10 mg/kg p.o.
      of NAGly were increased significantly by more than 9-fold when compared with
      vehicle-treated controls. In vitro evidence in RAW 264.7 cells using a deuterium
      labeled NAGly demonstrated that it was not a precursor or source of arachidonic
      acid for the observed 50% rise in anandamide levels, suggesting that the increase
      was due to some effect other than increased biosynthesis of anandamide. Moreover,
      the findings presented here suggest that NAGly can serve as a model for the
      design of agents to provide pharmacological control of tissue anandamide
      concentrations.

PMID- 12234619
TI  - Inhibition of cytochrome P450 2E1 by propofol in human and porcine liver
      microsomes.
AB  - While almost anesthetics are metabolized by the cytochrome P450 (CYP) 3A4, some
      major volatile ones such as halothane and sevoflurane are metabolized by CYP2E1
      in humans. To determine whether 2,6-diisopropylphenol (propofol), a widely used
      intravenous anesthetic agent, known to inhibit CYP3A4 and CYP1A2, also inhibits
      CYP2E1, 6-OH hydroxylation of chlorzoxazone, a prototypical CYP2E1 substrate, was
      estimated using two pools of human microsomes and one pool of porcine microsomes
      from seven livers. Basal human enzyme activities were characterized by a V(max)
      of 1426+/-230 and 288+/-29 pmol min(-1)mg(-1) protein and a K(m) of 122+/-47 and
      149+/-42 microM, while the corresponding porcine activities were associated with
      a V(max) of 352+/-42 pmol min(-1)mg(-1) protein and a K(m) of 167+/-38 microM. A
      competitive inhibition of CYP2E1 by propofol was observed with low inhibition
      constants in the therapeutic range in both porcine (19 microM) and human (48
      microM) liver microsomes. These in vitro results suggest that propofol could have
      a protective effect on toxic metabolite activation of compounds catalyzed by
      CYP2E1.

PMID- 12234620
TI  - Contribution of different phospholipases and arachidonic acid metabolites in the
      response of gallbladder smooth muscle to cholecystokinin.
AB  - Guinea pig gallbladder muscle strips were used to investigate the contribution of
      different sources of diacylglicerol (DAG) in the cholecystokinin (CCK)-induced
      contraction. The involvement of arachidonic acid (AA) in this response was also
      investigated. Three distinct pathways for DAG production were investigated with
      specific phospholipase (PL) inhibitors. U-73122 (10 microM) was used for
      inhibition of phosphoinositide-specific-PLC (PI-PLC), D-609 (100 microM) for
      phosphatidylcholine specific-PLC (PC-PLC), and propranolol (100 microM) for
      phospholipase D (PLD). Separate or combined inhibition of each of these enzymes
      showed that the CCK-induced output of DAG involves the parallel activation of
      each of these phospholipases. Thus, after inhibition of a PL subtype, the
      remaining subtypes were able to functionally compensate in mediating CCK-induced
      contraction. Inhibition of AA production via DAG-lipase or phospholipase A(2)
      (PLA(2)) was accomplished using RHC-80267 (40 microM), mepacrine (100 microM) and
      4-BPB (100 microM). These inhibitors diminished contractile response, indicating
      that AA is an important modulator of CCK-induced contraction. Indomethacin (10
      microM) and nordihydroguaiaretic acid (NDGA, 100 microM), which inhibit
      subsequent steps in AA metabolism through the cyclooxygenase and 5-lipooxygenase
      pathways, also inhibited contractions. Taken together, these results show that
      CCK redundantly activates PC-PLC, PI-PLC and PLD, to produce DAG, which in turn
      stimulates PKC and provides a substrate for the generation of AA. sPLA(2) is also
      a source of AA, whose metabolites are, in part, responsible for determining the
      magnitude of the CCK-evoked contraction.

PMID- 12234621
TI  - Cyclic AMP differentially modulates CD40L expression on human nai;ve and memory
      CD4(+) T cells.
AB  - Although differences in nai;ve and memory T cell signaling have been recognized,
      how these differences relate to cell regulation and function is not well
      understood. In this study, we investigated CD40 ligand (CD40L) regulation by
      cyclic AMP (cAMP) and prostaglandin E(2) (PGE(2)) and observed differential
      effects depending upon the cell subset and mode of activation. cAMP inhibited CD3
      induced CD40L in both nai;ve and memory subsets, although greater inhibition was
      observed in memory cells. With CD3/CD28 costimulation, cAMP inhibited CD40L in
      memory cells but had a minimal effect on nai;ve cells. In primed T cells, cAMP
      increased CD40L on nai;ve cells but inhibited expression on memory cells.
      Differential cAMP effects appear interrelated to calcium signaling since the
      level of CD40L induced by calcium ionophore was increased by cAMP in both cell
      subsets, although nai;ve cells were more calcium responsive. Calcium-dependent
      calcineurin activity appeared necessary for CD40L expression, although no
      interaction of calcineurin and cAMP regulation was demonstrable. In contrast,
      inhibitors of Ca(2+)/calmodulin-dependent protein kinase IV (CaMKIV) blocked cAMP
      effects to increase CD40L and resulted in marked CD40L inhibition. The importance
      of CaMKIV in cAMP regulation was confirmed by transfection studies using a
      dominant negative CaMKIV construct. We conclude that cAMP differentially
      regulates CD40L expression in a manner that appears dependent upon CaMKIV
      activation. In view of the central role of CD40L expression in immunity as well
      as the pathophysiology of common diseases, it is of interest that cAMP can either
      increase or decrease CD40L expression depending upon the T cell subtype and
      mechanism of cell activation.

PMID- 12234622
TI  - Biochemical and biological properties of phospholipases A(2) from Bothrops atrox
      snake venom.
AB  - Phospholipases A(2) (PLA(2)s), of molecular mass 13-15kDa, are commonly isolated
      from snake venom. Two myotoxins with PLA(2) activity, BaPLA(2)I and BaPLA(2)III,
      with estimated molecular masses of 15kDa were isolated from the venom of Bothrops
      atrox using Sephacryl S-100-HR and reverse-phase chromatography. BaPLA(2)I was
      basic, with a pI of 9.1, while BaPLA(2)III was neutral with a pI of 6.9. On a
      molecular basis, BaPLA(2)III exhibited higher catalytic activity on synthetic
      substrates than BaPLA(2)I. Comparison of the N-terminal residues of BaPLA(2)I
      with other PLA(2) proteins from snake venoms showed that it has the highest
      homology (94%) with B. asper myotoxin II and homology with a PLA(2) Lys(49) from
      B. atrox (89%). In contrast, BaPLA(2)III demonstrated 75, 72, and 71% homology
      with PLA(2) from Vipera ammodytes meridionalis, B. jararacussu, and B. jararaca,
      respectively. BaPLA(2)I and BaPLA(2)III were capable, in vitro, of inducing mast
      cell degranulation and, in vivo, of causing creatine kinase release, edema, and
      myonecrosis typical of PLA(2)s from snake venoms, characterized by rapid
      disruption of the plasma membrane as indicated by clumping of myofilaments and
      necrosis of affected skeletal muscle cells. BaPLA(2)I- and BaPLA(2)III-specific
      monoclonal and polyclonal antibodies, although incapable of neutralizing PLA(2)
      edematogenic activity, blocked myonecrosis efficiently in an in vivo
      neutralization assay. The results presented herein suggest that the biological
      active site responsible for edema induction by these two PLA(2) enzymes is
      distinct from the myonecrosis active site and is not dependent upon the catalytic
      activity of the PLA(2) enzyme.

PMID- 12234623
TI  - Role of mast cell chymase in allergen-induced biphasic skin reaction.
AB  - Intradermal injection of human chymase (EC 3.4.21.39) into the mouse ear elicited
      an edematous skin reaction in a biphasic manner, with a transient reaction
      peaking at 1 hr, followed by a delayed response persisting for at least 24hr. The
      kinetics of this reaction was analogous to the biphasic skin reaction induced by
      ascaris extract in actively sensitized mice. A similarity between the two
      dermatitis models was also shown by histological analysis, i.e. accumulation of
      inflammatory cells was observed exclusively in the later phases of the skin
      reaction. A chymase inhibitor, SUN-C8077 [3-(3-aminophenylsulfonyl)-7
      chloroquinazorine 2,4(1H, 3H)-dione], significantly inhibited both the early- and
      late-phase responses of the skin reaction induced by ascaris extract. These
      findings suggest that chymase may play an important role in the allergen-induced
      biphasic skin reaction. A histamine receptor antagonist, homochlorcyclizine,
      inhibited the early-phase but not the late-phase of the chymase-induced skin
      reaction. In addition, human chymase showed chemotactic activity to human
      polymorphonuclear leukocytes in vitro. Mast cell chymase may participate in the
      two phases of allergic skin inflammation by two distinct mechanisms, i.e.
      histamine- and leukocyte-dependent mechanisms, respectively.

PMID- 12234624
TI  - Some new aspects of 17alpha-estradiol metabolism in man.
AB  - 17Alpha-estradiol (1,3,5(10)-estratriene-3,17alpha-diol) together with a tracer
      dose of the tritium-labeled compound was administered orally and sublingually to
      male volunteers. The serum concentrations of 17alpha-estradiol (free and
      liberated by enzymatic hydrolysis) were quantified by GC/MS, and the serum total
      radioactivity and urinary radioactivity excretion were determined. After oral
      administration, 17alpha-estradiol was rapidly and intensively conjugated; only
      tiny quantities of the free steroid (<1% of total) appeared in serum. Sublingual
      administration resulted in temporary (up to 3 h p.a.) higher serum levels of the
      free compound. The metabolite patterns obtained by TLC of extracts from serum and
      urine demonstrated that 17alpha-estradiol is the subject of a poor phase I
      metabolism in man. A great discrepancy was found in the serum concentrations of
      17alpha-estradiol (free + conjugated) determined by GC/MS and the serum
      radioactivity expressed in 17alpha-estradiol equivalents. By TLC analysis of the
      steroid conjugates extracted from serum, various 17alpha-estradiol conjugate
      peaks were found. By enzymatic hydrolysis with beta-glucuronidase/aryl sulfatase
      from Helix pomatia they were only partially cleaved. Thus, the difference between
      the serum radioactivity and the 17alpha-estradiol levels determined by GC/MS had
      to be attributed to an incomplete conjugate hydrolysis. It has been shown with
      the synthesized 17alpha-estradiol sulfate conjugates that only the 3-sulfate is
      cleaved by enzymatic hydrolysis, whereas the 17-sulfate group resists enzymatic
      hydrolysis. The methanolysis procedure (acetyl chloride in MeOH) has proved to be
      an efficient method for cleaving both the 3-sulfate group and the 17-sulfate
      group. In contrast to the 17alpha-estradiol conjugates in serum, the urinary
      conjugates were intensively split by the enzyme preparation. From this, it has to
      be concluded that the serum conjugates were deconjugated and newly reconjugated
      before urinary excretion.

PMID- 12234625
TI  - Dexamethasone and retinoic acid differentially regulate growth and
      differentiation in an immortalised human clonal bone marrow stromal cell line
      with osteoblastic characteristics.
AB  - Clonogenic immortalised human pre-osteoblastic cell lines provide useful species
      specific experimental tools for the study of the regulation of osteoblastic
      proliferation and differentiation. Steroid hormones are major regulators of bone
      formation. Although much is known about the effects of dexamethasone on
      osteoblastic growth and differentiation in vitro, there is less information on
      the effects of trans-retinoic acid (RA), particularly in human cultures. We have
      established a clonal adult human cell line (C1) derived from a bone marrow
      aspirate. The cell line appeared to be bi-potential. The cells were able to
      differentiate into an adipocytic phenotype under appropriate culture conditions.
      When grown in osteogenic medium, the cells expressed alkaline phosphatase (ALP)
      and osteocalcin mRNA. The C1 cells also expressed several other osteoblastic
      markers such as collagen type 1 (COL 1), PTH/PTH-rp receptor constitutively.
      Transcripts for the osteoblast transcription factor Cbfa1 was also detected under
      basal conditions. In addition treatment with 1,25(OH)(2)D(3) (10(-7)M) led to a
      marked increase in osteocalcin mRNA expression suggesting that this cell line
      represents a pre-osteoblastic population. We compared the effects of Dex and RA
      on osteoblastic function. For the assessment of PTH/PTH-rp receptor, osteocalcin
      and Cbfa1 mRNA expression and PTH-stimulated adenylate cyclase responsiveness,
      the cells were grown in the presence of Dex and RA and harvested on Days 1, 3, 7
      and 14. RA (10(-7)M) had a mitogenic effect on the C1 cells. In contrast, Dex
      (10(-7)M) inhibited proliferation. A similar effect was observed with primary
      human bone marrow stromal cultures. Both Dex and RA inhibited COL 1 synthesis and
      decreased COL1 mRNA. Dex stimulated ALP activity and increased ALP mRNA
      expression whilst RA had an inhibitory effect. Dex treatment led to an increase
      in PTH/PTH-rp receptor mRNA and PTH-induced cAMP accumulation with a peak
      response at 24 h and this effect was sustained for up to 14 days. In contrast,
      long-term culture with RA resulted in a reduction in the cAMP response to PTH
      (Days 7 and 14) with no effect on PTH/PTH-rp receptor mRNA expression.
      Osteocalcin and Cbfa1 mRNA expression did not alter in the presence of Dex and RA
      at these time points. This study shows that Dex and RA have differential effects
      on the expression of the phenotypic markers and genes associated with osteoblast
      maturation. This homogeneous cell line can therefore be used further to elucidate
      the cellular and molecular mechanisms of action of Dex and RA at the different
      developmental stages of human osteoblastic differentiation. This cell line may
      thus provide a useful species-specific in vitro model for the evaluation of key
      genes and signalling molecules involved in osteogenesis. This would be of help in
      the design of 'in vivo' studies.

PMID- 12234626
TI  - On the structures of hydroxylated metabolites of estradiol 17-sulfate by rat
      liver microsomes.
AB  - The metabolism of estradiol 17-sulfate (ES) by hepatic microsomes of female rats
      produced four new metabolites in addition to 2- and 4-hydroxyestradiol 17
      sulfates (2- and 4-OH-ES), which were detected on an HPLC chromatogram. By
      comparison with synthetic specimens, three of these compounds were identified as
      6alpha-, 6beta-, and 7beta-hydroxyestradiol 17-sulfates. To elucidate the
      structure of the remaining metabolite, a large-scale incubation of ES was carried
      out, followed by isolation using preparative HPLC to give the single material,
      which was assigned as 15beta-hydroxyestradiol 17-sulfate by instrumental
      analyses. On the other hand, when ES was incubated with the microsomes of male
      rats, 2-OH-ES was produced accompanied by two minor products: 4-OH-ES and a
      metabolite of unknown structure. The results show clearly that the metabolism of
      ES by rat hepatic microsomes is remarkably different between the sexes.

PMID- 12234627
TI  - Ternary gradient elution markedly improves silver-ion high performance liquid
      chromatography of unsaturated sterols.
AB  - A wide variety of unsaturated sterols can accumulate in eukaryotic cells as a
      consequence of normal metabolism, genetic disorders, and actions of enzyme
      inhibitors. Resolving these sterol mixtures into individual components by
      conventional chromatographic methods is inefficient because unsaturated sterols
      differ little in polarity, hydrophobicity, and volatility. Although sterol
      mixtures are well-resolved by silver-ion high performance liquid chromatography
      (Ag(+)-HPLC), existing methods require derivatization to acetates for best
      results, and the isocratic mobile phases lead to long analysis times and low
      sensitivity for late-eluting sterols. We show that these problems can be overcome
      with ternary gradient elution using acetone, hexanes, and acetonitrile.
      Separation of a mixture of 20 underivatized sterols gave dramatically shortened
      analysis times, with good peak shapes for both early- and late-eluting
      components. In a similar separation of blood sterols from a patient with Smith
      Lemli-Opitz syndrome, the band for 7-dehydrocholesterol was much narrower than
      with isocratic elution. Column re-equilibration was rapid, and the separations
      could be monitored with ultraviolet spectroscopy at 210 nm, which affords
      universal, non-destructive detection of unsaturated sterols. Also discussed are
      retention mechanisms and reproducibility of Ag(+)-HPLC separations. The overall
      results represent a major advance in chromatographic methods for resolving
      mixtures of unsaturated sterols differing in the number and position of olefinic
      bonds.

PMID- 12234629
TI  - Identification of intrinsic and reflexive components of human arm dynamics during
      postural control.
AB  - In this study a new methodology to quantify reflexive feedback gains from the
      mechanical behavior of the human arm during posture maintenance is proposed.
      Disturbance experiments were carried out on human subjects using continuous
      random force inputs. The task instruction was 'minimize displacements',
      prescribing a maximum performance task. For the separation of intrinsic and
      reflexive components, system identification in the frequency domain is applied.
      From the time records of position and force, frequency response functions (FRFs)
      are estimated. Given a model structure and an appropriate estimate of the
      intrinsic component, an estimate of the reflex gains for length and velocity are
      obtained from the FRFs. The feedback gains vary considerably with the frequency
      content of the disturbance signal. The results show that reflexive dynamics are
      substantial for narrow-band and especially low-frequency input signals. It is
      likely that high reflex gains are most effective for low-frequency inputs (< 3
      Hz) that do not excite the closed-loop system's eigenfrequency. Also significant
      negative reflex gains are estimated for near-sinusoidal inputs (> 1.5 Hz). It is
      concluded that this new methodology can offer interesting insights into the
      ability of the central nervous system to modulate reflexive feedback gains.

PMID- 12234628
TI  - Developmental regulation of intracellular and surface androgen receptors in T
      cells.
AB  - Increasing information indicates that testosterone actions on cells are mediated
      not only through the classical intracellular androgen receptor (iAR), but also
      through membrane androgen receptors (mAR) on cell surfaces. Here, we investigate
      the expression pattern of mAR and iAR in thymic T cells, which is compared with
      that of splenic T cells. Thymic T cells are testosterone-sensitive in vivo, i.e.
      treatment of female C57BL/10 mice with testosterone for 3 weeks decreased the
      total number of thymic T cells by approximately 90%. The percentage of CD4(-)
      CD8(-) T cells increased, whereas that of the subsequent CD4(+) CD8(+) T cells
      was diminished. Flow cytometry and confocal laser scanning microscopy (CLSM) with
      different anti-iAR antibodies localized iAR predominantly in the cytoplasm, but
      not on the surface of thymic T cells. The iAR are functionally active since the
      iAR are induced by testosterone to translocate from cytoplasm to nucleus, and
      they bind the testosterone analogue 3H-R1881 with high affinity (K(d)
      approximately 2.2 nM) and saturable capacity (approximately 10,000 binding sites
      per cell) as determined by Scatchard analysis. By contrast, the impeded ligand
      testosterone-BSA-FITC (T-BSA-FITC) did not bind to the surface of thymic T cells.
      In accordance, testosterone was unable to induce any rapid rise in the
      intracellular free Ca(2+) concentration of Fura-2 loaded thymocytes. This
      indicates that thymic T cells do not express any significant amounts of mAR.
      Conversely, splenic T cells express functionally active mAR, whereas their
      expressed iAR are not functional in the genomic pathway. Our results support the
      view of a delicately balanced developmental regulation of iAR and mAR in T cells.

PMID- 12234630
TI  - Somatotopic organization of rat thalamocortical slices.
AB  - The thalamocortical slice is widely employed for in vitro studies of cortical
      circuits. This preparation was developed in order to preserve anatomical and
      functional connectivity between the ventrobasal thalamus and somatosensory
      (whisker/barrel) cortex of young mice, and thalamocortical slice experiments have
      contributed significantly to our understanding of the thalamocortical synapse.
      Cortical somatotopy within thalamocortical slices, however, has not been
      characterized, and this greatly limits their use in studies that require
      identification of cortical areas associated with particular regions of the
      sensory periphery. To address this shortcoming we used electrophysiological
      recording and neuroanatomical labeling techniques in rats to mark the position of
      functionally defined whisker barrels, in vivo. We subsequently processed the
      brains in a plane appropriate for TC slices and characterized the location of
      somatotopically identified barrels in relation to other aspects of slice
      topology. We found that barrels associated with the large mobile whiskers occupy
      a particular location in TC slices, but that there are certain constraints to
      studying this portion of the barrelfield in vitro.

PMID- 12234631
TI  - Intracellular injection in fixed slices: obtaining complete dendritic arbors of
      large cells.
AB  - Intracellular injection of Lucifer yellow into fixed brain slices is widely used
      to demonstrate dendritic morphology. A major limitation of this technique is that
      large dendritic arbors are usually truncated at the cut surfaces. Here we
      describe modifications that allowed us to obtain complete dendritic arbors of
      large spiny stellate cells. Lucifer Yellow cadaverine biotin-X (LY-X) was
      injected into individual neurons within 300-1000 microm thick aldehyde-fixed
      slices of kitten visual cortex. Subsequently, the LY-X was histochemically
      reacted using standard ABC methods to obtain a permanent record of the injected
      cells. Dendrites, studded with a variety of dendritic spines, were darkly labeled
      and well defined against virtually no background. Somatic spines, dendritic
      varicosities and growth cones were common in the younger animals. Computer
      assisted reconstructions demonstrated that, in older animals, the dendritic
      arbors of cells injected in 300 microm slices were truncated, whereas the arbors
      of cells injected deep within thick slices were complete. The modifications
      described here remove the most critical limitation of intracellular injection in
      slices, allowing quantitative analysis of even large dendritic arbors.

PMID- 12234632
TI  - Simultaneous HPLC quantification of monoamines and metabolites in the blood-free
      rat cochlea.
AB  - Monoamine quantification in peripheral sensory receptors, such as the cochlea, is
      of major interest since monoamines could play a role in neurotransmission. A
      three-step biochemical protocol was developed to analyze monoamine content within
      the cochlea. Removal of the blood by aortic perfusion was carried out with an
      anticoagulant solution prior to the dissection of the cochlea from the temporal
      bone. The cochlear monoamines and some of their metabolites were then quantified,
      from homogenated cochlear tissue, by a new application of high performance liquid
      chromatography coupled to electrochemical detection. This method demonstrated
      enough sensitivity to detect norepinephrine (NE), dopamine (DA), serotonin (5-HT)
      and some of their metabolites (3,4-dihydroxyphenylacetic acid, DOPAC;
      homovanillic acid, HVA; and 5-hydroxyindole-3-acetic acid, 5-HIAA). Furthermore,
      it enabled the demonstration of noise-induced changes in the cochlear
      concentrations of NE, DA, DOPAC and HVA. In addition, the aortic perfusion
      allowed removal of the blood-borne 5-HT from the cochlea without inducing
      systemic alterations or monoamine degradation, as shown by the absence of effects
      on NE, DA, DOPAC, HVA or 5-HIAA concentrations. The present methodology may
      constitute a useful strategy to analyze monoamine turnover in the cochlea and
      other peripheral sensory receptors.

PMID- 12234633
TI  - Imaging calcium dynamics in the nervous system by means of ballistic delivery of
      indicators.
AB  - The use of fluorescence-based calcium indicators has, over the years, unraveled
      important calcium-dependent mechanisms underlying neuronal function and
      development. However, difficulties associated with the loading of calcium
      indicators have limited their widespread use, particularly for the study of
      neuronal processing in the adult nervous system. Here, we show that in the
      central and peripheral nervous systems, populations of neurons and their
      processes, including dendritic spines and filopodia, can be labeled rapidly and
      efficiently by delivering calcium indicator-coated particles using a 'gene gun'.
      Importantly, neuronal labeling occurred both in vitro and in vivo, and across a
      wide range of ages and preparations. The labeled cells demonstrate spontaneous
      and evoked calcium transients, indicating that particle-mediated delivery is not
      deleterious to neuronal function. Furthermore, unlike loading with patch
      pipettes, cytoplasmic content is preserved following ballistic loading. This
      enables the study of calcium-dependent second messenger pathways without loss of
      signaling components. The ballistic delivery of calcium indicators thus opens up
      many new avenues for further exploration of the structure and function of the
      nervous system from single spines to neuronal networks.

PMID- 12234634
TI  - A microdialysis method for the recovery of IL-1beta, IL-6 and nerve growth factor
      from human brain in vivo.
AB  - Intracerebral microdialysis is used extensively as a research tool in the
      investigation of the neurochemical and metabolic changes that occur following
      acute brain injury. Microdialysis has enabled elucidation of intra-cerebral
      levels of substances such as lactate, pyruvate and glycerol but, as yet, has not
      been used effectively to recover macromolecules from the human brain. Traumatic
      brain injury is known to result in the generation of cytokines and neurotrophins
      into extracellular fluid compartment of the brain, with effects on neuronal
      damage and repair. We have developed a technique of in vivo sampling of the
      interstitial fluid of the brain of patients with severe head injuries which has
      allowed the measurement of IL-1beta, IL-6 and nerve growth factor. This report
      confirms the safety and effectiveness of this modified microdialysis method in
      the clinical setting of a neurological intensive care unit. The technique
      provides a timely addition to the armamentarium of the clinical scientist and
      will potentially lead to a greater understanding of neuroinflammation following
      acute traumatic brain injury.

PMID- 12234635
TI  - Development of a novel experimental rat model for neonatal pre-ganglionic upper
      brachial plexus injury.
AB  - A neonatal upper brachial plexus injury, referred to as Erb's palsy, is a serious
      obstetric problem. Some surgical methods are used to treat this injury, but they
      are inadequate. To seek new treatments for Erb's palsy, we used a model for
      cervical preganglionic root transection in neonate rats and evaluated the
      behavioral and histological compatibility of this model with Erb's palsy. Two
      groups were used in this study. In the group, receiving the Erb operation, the
      left anterior and posterior roots of spinal vertebra C5-C7 were transected at the
      preganglionic level, and the results were compared with those of a group that
      received a sham operation. In the group, receiving the Erb operation, walking
      difficulties and behavioral abnormalities were observed. These observations were
      noted on the side where the transection took place, and the problems were
      attributed to proximal muscle weakness in the forelimb. Additionally, the forepaw
      grip was not impaired. Furthermore, in this group, the number of anterior horn
      cells in the cervical cord on the transected side was significantly lower than
      that on the contralateral side (P < 0.001). The results of this study indicate
      that the model fulfills the criteria for the clinical symptoms of Erb's palsy and
      that it may also serve as a new method for enabling treatment of the condition.

PMID- 12234636
TI  - Ultrastructural identification of dividing cells in the adult mammalian central
      nervous system.
AB  - In most parts of the adult mammalian central nervous system cell division is a
      relatively rare event, which makes it difficult to study at the ultrastructural
      level. We designed a protocol for reliable ultrastructural identification of
      proliferating cells in a tissue volume using DNA-incorporated 5-bromo-2
      deoxyuridine (BrdU) as a marker. After BrdU administration the tissue is fixed
      and embedded in hydrophilic resin (LR Gold) and then cut in serial 1-2 microm
      sections and mounted on glass slides. BrdU is detected at the light microscopic
      level using immunogold labeling followed by silver enhancement, according to a
      standard procedure. After detection of labeled nuclei the section is reembedded
      in resin on the same glass slide. The glass is then dissolved in hydrofluoric
      acid and labeled cells cut in ultrathin sections for further ultrastructural
      analysis. The technique was tested and refined in sections of the intestine
      containing numerous dividing cells and, once optimized, was then applied to
      identify the ultrastructure of slowly proliferating putative stem cells in the
      adult mouse spinal cord.

PMID- 12234637
TI  - Quantifying axial secretory-granule motion with variable-angle evanescent-field
      excitation.
AB  - The trajectory of secretory vesicles to their fusion sites at the plasma membrane
      is expected to give insight into the mechanisms that underlie vesicle transport,
      maturation and the initiation of membrane fusion. Evanescent-wave (EW) microscopy
      allows the tracking of fluorescently labeled granules and vesicles prior to
      fusion with nanometer precision in xy-direction. At the same time, the
      exponential sensitivity of granular fluorescence to experimental parameters can
      preclude quantitative estimates of the granule's approach to the plasma membrane.
      Thus, it has remained controversial to which extent axial distance can be
      obtained from simple intensity measurements. We used the information contained in
      a stack of images acquired at 80-125 nm penetration depth of the EW field to
      estimate individual granule diameter and axial distance. A population analysis on
      90 granules revealed an average diameter of 305 +/- 47 nm, below the diffraction
      limited 352 +/- 31 nm obtained from xy measurements at fixed depth penetration.
      Stimulation of exocytosis by potassium depolarization resulted in the selective
      loss of the 18 +/- 5% of granules located closest to the plasma membrane, while a
      second population of granules located 60 nm deeper within the cytoplasm increased
      by recruitment of granules previously located at > or = 120 nm depth. These
      measurements extend and corroborate previous observations at fixed penetration
      depth of functionally distinct granule populations. Parameters influencing the
      accuracy of the parameter estimation are evaluated in the appendix.

PMID- 12234638
TI  - Carbon fiber microelectrodes with multiple sensing elements for in vivo
      voltammetry.
AB  - Electrically evoked dopamine release was monitored in the striatum of
      anesthetized rats using voltammetric microelectrode assemblies with two to four
      separately addressable carbon fiber sensing elements. The sensing elements were
      disk-shaped, had a diameter of about 1 microm, and were separated from each other
      by less than 15 microm. The microelectrodes were used to monitor extracellular
      dopamine at multiple depths beneath the brain surface during electrical
      stimulation of the medial forebrain bundle. When the sensing elements were 10-15
      microm apart, the stimulus responses at each element were distinct, suggesting
      that each response was representative of a distinct recording site. The
      possibility of performing measurements at distinct but closely spaced sites
      provides a potential route to high spatial resolution information about
      extracellular events. On the other hand, when the individual sensing elements
      were about 1 microm apart, similarities between the observed stimulus responses
      suggest that the multiple elements were recording from a single site. The ability
      to perform multiple chemical measurements at a single site presents several
      opportunities for new approaches to the in vivo study of neurochemistry.

PMID- 12234639
TI  - Comparison of intracranial pressure measured in the cerebral cortex and the
      cerebellum of the rat.
AB  - In this study, we evaluated the accuracy of intracranial pressure (ICP)
      measurement in rats by insertion of a miniature ICP probe in the parenchyma of
      the cerebellum. A comparison was made between the ICP values measured
      simultaneously in the parenchyma of the cerebral cortex and the cerebellum. In
      order to obtain a wide range of ICP, animals were subjected to a severe closed
      head injury (CHI), a moderate CHI or to a sham operation. ICP values ranged from
      0.8 to 43.9 mmHg. After 15 min stabilisation the first measurement was taken and
      followed by a second measurement 25 min after onset to allow comparison of ICP
      changes at the two implantation sites. Linear regression analysis showed a highly
      significant correlation at 15 min: Y = 0.919X + 0.655 (R(2) = 0.977), and at 25
      min: Y = 0.931X + 0.698 (R(2) = 0.976). The differences in ICP measurement
      between cerebellar and cerebral site were not significantly different from zero
      at both time points. Altman-Bland plots showed that the difference in ICP
      readings between the two locations could differ maximally by 5.3 mmHg. The
      largest differences were detected when high ICP values were recorded. We conclude
      that in rats the ICP measurement in the cerebellum is comparable to the ICP
      measurement in the cerebral cortex. The cerebellar ICP can be used as a valuable
      alternative during experimental procedures.

PMID- 12234640
TI  - A discovery of new features of gastropod local field potentials by application of
      wavelet tools.
AB  - Odor input evokes characteristic, time-evolving (non-stationary) events in the
      spontaneously active central ganglia of the snail Helix pomatia. Assuming
      stationarity for the signals, one could, as the first approach, apply the Fourier
      based methods, frequency amplitude characteristics (FAC) measures, for analyzing
      such events. We could thus for the first time describe such events in frequency
      and amplitude and show that the frequency, at which power increases most, is
      specific to the odor or its class [Comp. Biochem. Physiol. 123A (1999a) 95; Comp.
      Biochem. Physiol. 124A (1999b) 297]. Wavelet tools assume no record stationarity
      and are suitable for describing the dynamically evolving brain electrical signals
      precisely and quantitatively. We, therefore, tested these tools for the typical
      odor experiments with the procerebrum (PC), the pedal ganglion (PG) and the
      visceral ganglion (VG) of the Helix, which we earlier analyzed by the FAC
      measures and compared both results. The two basic findings of the present wavelet
      analysis are as follows: (i) the wavelet energy fluctuations clearly visualize
      dynamical interactions among the major bands (0.1-3.1 Hz), implying a possible
      'mutual exclusion' between slow components < 0.8 Hz and faster ones > 0.8 Hz.
      (ii) Entropy behavior was characteristically different for each of the three
      brain regions. Only in PC the response to aversive odorants (decrease of entropy
      = more ordered state) is differentiated in entropy from that to attractive ones
      (increase of entropy=more disordered or more complexly ordered state) indicating
      the odor-discriminating function of this region. In VG entropy of the intrinsic
      activity is so high (highly disordered state) due to the strong wideband activity
      reaching > 50 Hz that odor stimulation results mainly in lowering of entropy (=
      more ordered state) regardless of the nature of the odor. In PG, however, odor
      presentation generally increases entropy due to the robust, wide-band activation
      at > 3 Hz (sensorimotor function) that is generated as a secondary, but dominant
      and robust, response. In respect to describing time evolution of different
      frequency band components the present wavelet tools can much more sensitively do
      so, as compared with the FAC measures. They can also characterize a change in the
      neuroelectrical state in terms of entropy.

PMID- 12234642
TI  - Clinical impairment of benzodiazepines--relation between benzodiazepine
      concentrations and impairment in apprehended drivers.
AB  - BACKGROUND: Acute intake of benzodiazepines is followed by concentration
      dependent deterioration of performance in controlled experimental studies.
      Whether this is true in a population of benzodiazepine users is uncertain. We
      studied the relationship in a population of suspected drugged drivers. METHODS:
      In Norway physicians examine and take blood samples from nearly all suspected
      drivers. Our material comprised 818 samples containing only one benzodiazepine
      and our reference group consisted of 10,759 cases containing only alcohol.
      RESULTS: 159 drivers (19%) were considered as not impaired and 659 (81%) as
      impaired. None of the background factors, e.g. gender, age or time of day when
      apprehended, related significantly to either the physician's conclusion or to
      blood levels of benzodiazepines. Impaired subjects had significantly higher blood
      levels of diazepam (n=411) (P<0.001), oxazepam (n=73) (P<0.05) and flunitrazepam
      (n=211) (P<0.05) than those not impaired. The risk of being assessed as impaired
      did rise with increasing benzodiazepine blood level, with odds ratios (ORs) for
      being assessed as impaired of 1.61, 3.65 and 4.11 for the three supratherapeutic
      drug levels. The corresponding OR found for different elevated blood-alcohol
      concentrations were 1.49, 2.94 and 10.49. CONCLUSION: The blood concentration of
      benzodiazepines was the only characteristic which was related to impairment. This
      indicated a drug-concentration related effect of benzodiazepines on performance
      and paves the way for a discussion on legal limits for benzodiazepines in
      relation to driving.

PMID- 12234641
TI  - Intention-to-treat meets missing data: implications of alternate strategies for
      analyzing clinical trials data.
AB  - True intention-to-treat analyses are rare in reports of randomized clinical
      trials. To highlight the complex issues that arise in conducting and interpreting
      data from intention-to-treat analyses in studies with substantial levels of
      protocol violation (e.g. attrition, noncompliance, or withdrawal of
      participants), data from a clinical trial of treatment for cocaine dependence
      were analyzed using three strategies to manage missing data: Strategy 1 addressed
      the effectiveness of treatments based on data collected from participants up to
      the point of dropout. Strategy 2 addressed the effectiveness of treatments based
      on data from the full intended duration of the protocol including data collected
      after participant dropout. The third strategy used a more novel approach, which
      used an intention-to-treat strategy for the full duration of the trial and the
      full sample, but also evaluated the effect of treatment retention outcomes by
      including an independent variable to reflect active treatment retention as a time
      varying covariate. Conclusions about the relative efficacy of the study
      treatments varied to some extent depending on the analytic strategy used. These
      findings suggest that investigators should make every effort to conduct intent-to
      treat analyses, but also to make use of multiple analytic strategies to fully
      understand the effects of the treatments studied. Moreover, regardless of the
      strategy used, investigators should clearly describe their handling of data from
      participants who violate the protocol.

PMID- 12234643
TI  - Increased mortality among previously apprehended drunken and drugged drivers.
AB  - Most studies in the field of impaired driving have focused on the hazards imposed
      on society by the impaired drivers, whereas little attention has been paid to the
      future outcome of the drivers. The aim of the study was to identify mortality
      rates and causes of death among drunken and drugged drivers during the years
      after apprehension. Prospective cohort study on apprehended drunken and drugged
      drivers, follow-up period: 7.5 years, outcome variable: death. Apprehended
      drivers 20-39 years old who provided samples positive for alcohol (n=2531) or
      drugs other than alcohol (n=918) constituting the total national samples of these
      two driver categories in 1992. The mortality rate among male drunken drivers was
      higher than in an age-matched Norwegian population (standardised mortality ratio,
      SMR=3.7 (95% Cl 2.9-4.7). The SMR for drugged drivers was 18.1 (14.9-21.8) for
      men and 27.9 (14.4-48.8) for women. In a subgroup of male drugged drivers using
      heroin, SMR was 39.8 (28.8-53.6). The dominant causes of death among drunken and
      drugged drivers were drug poisoning/overdose, accidents and suicide. Apprehension
      for drunken or drugged driving and subsequent analytical verification, is an
      indicator of increased risk of future premature death in the age group 20-39
      years, particularly for drugged drivers. To our knowledge this is a new finding,
      and studies to confirm it should be carried out in other countries. If verified,
      the results should lead to the consideration of new public health approaches
      towards apprehended impaired drivers.

PMID- 12234644
TI  - Status hearings in drug court: when more is less and less is more.
AB  - We examined the effects of increasing the number of times misdemeanor drug court
      clients appeared before a judge for judicial status hearings. Our previous
      findings showed no main effect of increased hearings during the first 14 weeks of
      the program. The present study examined participants' discharge status in the
      program, and also explored potential interactions between client characteristics
      and the frequency of judicial status hearings on outcomes. Results revealed no
      main effects for hearing frequency on graduation status. Drug offenders who
      satisfied DSM-IV criteria for antisocial personality disorder (APD) achieved more
      weeks of urinalysis-confirmed drug abstinence when assigned to more frequent
      judicial status hearings, whereas subjects without APD achieved more abstinence
      and were more likely to graduate successfully from the program when assigned to
      less frequent hearings. Additionally, clients with a history of substance abuse
      treatment achieved more weeks of abstinence when assigned to more frequent
      hearings. These findings lend useful guidance to drug courts. Status hearings are
      expensive and time consuming and should be targeted to clients who would benefit
      most from them.

PMID- 12234645
TI  - Predictors of drug abuse treatment entry among crack-cocaine smokers.
AB  - The goal of this study was to identify factors that predicted drug abuse
      treatment program entry among a community sample of 430 crack-cocaine users.
      Subjects were recruited using a targeted sampling methodology and responded to
      interviewer-administered questionnaires at 6 months intervals over a 3-year
      period. At baseline, 40.5% (n=174) reported they had never been in a drug abuse
      treatment program. During the observation period, 37.7% (n=162) of the sample
      reported they had entered a program. Of these, 43.8% (n=71) reported that their
      treatment was court-ordered. Slightly more than one-quarter (n=44) entered
      treatment for the first time. A host of variables, including individual
      characteristics, frequency and duration of crack use, frequency of drunkenness,
      Addiction Severity Index (ASI) family/social, medical, and psychiatric status
      composite scores, perceived need for treatment, history of treatment, and medical
      insurance coverage, was explored. The results of Cox proportional hazards model
      suggested that younger people, users with more severe legal problems, people who
      perceived a need for treatment, and individuals with prior treatment experience
      had a greater likelihood of entering treatment. Developing a strategy to
      practically apply these findings may facilitate treatment entry among a
      population involved with a dangerous and debilitating drug.

PMID- 12234646
TI  - What motivates adolescent smokers to make a quit attempt?
AB  - A sample of 120 adolescent smokers (80 males, 40 females), most of whom were
      referred by school personnel after being caught with cigarettes at school
      (n=113), reported motivations for making a quit attempt during a smoking
      cessation project. Most students (n=76) were randomly assigned to a four session
      cessation program that included discussion of a number of motivational topics,
      and the remaining students were assigned to a self-help control group that
      received a pamphlet recommending strategies for quitting. Reported motivations
      for quitting did not differ significantly across the two treatment conditions.
      Concern about future health (73%) was the most popular reason given for making a
      quit attempt, followed by concern about current health (65%). Concerns about
      physical appearance (59%), the cost of cigarettes (52%), and athletic performance
      (51%) were also listed as motivators by a majority of the participants. Future
      health was the most popular choice for the most important motivator to quit
      (35%). Females and participants with fewer best friends smoking were more likely
      to report that the prevalence of non-smoking teenagers, the relationship between
      smoking and weight, and physical appearance concerns were motivators to quit.
      African Americans were more likely than Whites to list current health concern as
      the most important motivator.

PMID- 12234647
TI  - Ketamine impairs multiple cognitive domains in rhesus monkeys.
AB  - Available evidence suggests that recreational use and abuse of the dissociative
      anaesthetic ketamine is increasing. Characterization of the cognitive risks of
      ketamine exposure contributes substantially to understanding this growing public
      health threat. Although prior human studies demonstrate that ketamine impairs a
      range of cognitive skills, investigation in nonhuman models permits more precise
      exploration of neurochemical mechanisms which may underlie detrimental behavioral
      effects. Adult male rhesus monkeys (N=7) were trained on a neuropsychological
      battery including tests of memory (delayed match-to-sample, DMS; self-ordered
      spatial search, SOSS), reaction time (RT), reinforcer efficacy and sustained
      attention (progressive ratio, PR) and fine motor coordination (bimanual motor
      skill, BMS). Battery performance was then serially challenged with acute doses of
      ketamine (0.3, 1.0, 1.78 mg/kg IM). Ketamine impaired DMS and SOSS in a dose x
      difficulty dependent manner with the most difficult task conditions disrupted at
      the 1.0 and 1.78 mg/kg doses. Thus, both visual recognition memory and working
      memory indices were affected. Ketamine also slowed RT and BMS performance and
      interfered with PR performance at the 1.78 mg/kg dose. Overall the present
      findings confirm that ketamine interferes with multiple aspects of cognition at
      subanesthetic doses in monkeys.

PMID- 12234648
TI  - Consequences of monosodium glutamate or goldthioglucose arcuate nucleus lesions
      on ethanol-induced locomotion.
AB  - It has been suggested that the endogenous opioid system, especially beta
      endorphins, may play an important role in the behavioral effects of ethanol. The
      main site of beta-endorphin synthesis in the brain is the hypothalamic arcuate
      nucleus (ARC). In the present study, we used the neurotoxins monosodium glutamate
      (MSG) or goldthioglucose (GTG) to produce a selective ARC lesion and to assess
      its effects on the locomotion observed after ethanol administration. The results
      show that MSG or GTG pre-treatment produces a blockade of the increased
      locomotion produced by the injection of low and moderate doses of ethanol (0.5
      and 1.5 g/kg, respectively). These effects were observed in the absence of any
      change in blood ethanol levels. On the other hand, MSG (but not GTG) pre
      treatment enhanced the locomotor depression produced by higher doses of this
      alcohol (2.5 g/kg). Finally, caffeine (10 mg/kg)-induced locomotion was
      unaffected by the aforementioned neurotoxic agents. Thus, taken together, the
      present results suggest that MSG and GTG administration produce a blockade of the
      stimulating effects of ethanol on locomotion in mice and thus provides further
      support for a role of the ARC in the behavioral effects observed after ethanol
      administration.

PMID- 12234649
TI  - Mental disorders in ecstasy users: a prospective-longitudinal investigation.
AB  - OBJECTIVES: To investigate the relationship between ecstasy use and mental
      disorders in a representative sample of adolescents and young adults. METHOD:
      Data for this investigation were drawn from the Early Developmental Stages of
      Psychopathology (EDSP) study, an epidemiological-longitudinal study in which 14
      24 year-olds were examined prospectively over a period of about 4 years. Results
      are based on N=2462 participants who completed the whole study period and for
      whom drug use behavior could be determined. RESULTS: (1). Ecstasy users, compared
      with non-users, were at significantly increased risk of DSM-IV substance related
      disorders, including alcohol use disorders (52.6 vs. 15.6%; OR=5.6, 95% CI=3.8
      8.1). Further, ecstasy users also had a higher risk of alcohol use disorders,
      when compared with users of other illicit substances (52.6 vs. 40.3%; OR=1.7, 95%
      CI=1.1-2.4). (2). Ecstasy users had significantly higher rates for almost all DSM
      IV mental disorders examined when compared with non-users (any non-substance use
      disorder: 68.7 vs. 44.5%; OR=3.1, 95% CI=2.1-4.4) and compared with users of
      other illicit drugs (any non substance use disorder: 68.7 vs. 55.5%; OR=1.8, 95%
      CI=1.2-2.6). (3). Ecstasy users also reported significantly higher rates of
      prescription medicine use, though they did not use more medical services than non
      drug users. (4). Analyses of temporal patterns of ecstasy use and disorder onset
      revealed that the first use of ecstasy was secondary to the onset of DSM-IV
      mental disorders in the majority of cases. Still, subjects with mental disorders
      at baseline also showed a significantly increased risk for initiation of ecstasy
      use during the 4-year follow-up period. CONCLUSIONS: Care should be taken in
      cross sectional studies in interpreting mental disorder signs and symptoms merely
      as a consequence of ecstasy use, as ecstasy use might be associated with the use
      of multiple substances, and onset of mental disorder is more likely to precede
      rather than to follow use of ecstasy and related substances.

PMID- 12234650
TI  - Development and psychometric properties of the Verona Service Satisfaction Scale
      for methadone-treated opioid-dependent patients (VSSS-MT).
AB  - We adapted the 32-item Verona Service Satisfaction Scale (VSSS-32) to assess
      opioid-dependent patient satisfaction with services received from methadone
      treatment centres. The preliminary version of the VSSS for methadone treatment
      (VSSS-MT) was filled out anonymously and completed by 516 randomly recruited
      patients. After exploratory factor analysis and item refinement, the definitive
      27-item VSSS-MT accounted for 58.8% of the total variance, comprising four
      factors: Basic Interventions, Specific Interventions, Social Worker Skills, and
      Psychologist Skills. These factors showed good to excellent internal
      reliabilities (Chronbach's alpha: 0.91, 0.85, 0.87, and 0.92, respectively). At
      test-retest, intraclass correlation coefficients of VSSS-MT overall and factor
      scores were fair to good. The results of this study suggest that the VSSS-MT
      measures, briefly but also multidimensionally, opioid-dependent patient
      satisfaction with methadone treatment centres.

PMID- 12234651
TI  - Impact of alcohol detoxification on anxiety and depressive symptoms.
AB  - Anxiety and depression are frequently encountered 'collateral' symptoms in
      alcohol abusing subjects. The present study investigated the effect of
      detoxification on these symptoms over 4-5 weeks of abstinence from alcohol.
      Psychopathology and global functioning were assessed at baseline and at weekly
      intervals over this period from 28 alcoholics treated on an inpatient basis. At
      intake, they displayed high levels of anxiety and depression; also, global
      functioning was seriously impaired. Following detoxification, scores on all
      measures of psychopathology were notably reduced. These findings allude to the
      depression-inducing properties of alcohol, which should be considered in the
      differential diagnosis of mood symptoms in alcohol abusing individuals.

PMID- 12234652
TI  - Chasing the dragon, related to the impaired lung function among heroin users.
AB  - AIM: To describe the pulmonary function and prevalence of dyspnoea among
      methadone patients and to study the relation with exposure to heroin by inhaling.
      STUDY POPULATION: A sample of 100 patients from methadone maintenance treatment
      (84% male, average age 42 years). MEASUREMENTS: Questionnaires were used to
      measure life-time exposure to heroin, cocaine, cannabis, tobacco, and symptoms of
      dyspnoea. Spirometry was performed and residual difference of measured FEV(1)
      from the age, sex, height and ethnicity predicted value (delta FEV(1)) was used
      as a main outcome parameter. FINDINGS: The median delta FEV(1) was -0.26 l (inter
      quartile range -0.70; +0.12). Twenty per cent experienced dyspnoea while 'walking
      at a normal pace with someone of their own age'. History of cigarette smoking was
      reported by 98%; heroin smoking by 88%. Multiple linear regression analysis
      showed a statistically significant association between heroin-smoking and delta
      FEV(1), logistic regression analysis showed an association between heroin-smoking
      and prevalence of dyspnoea. CONCLUSIONS: Chronic heroin smoking seems to be
      related to an impaired lung function and higher prevalence of dyspnoea. However,
      part of the observed lung function impairment will be caused by tobacco smoking.
      Further research is needed to quantify the effect of heroin smoking and
      disentangle the effect of smoking heroin and tobacco.

PMID- 12234653
TI  - EphA receptors and ephrin-A ligands exhibit highly regulated spatial and temporal
      expression patterns in the developing olfactory system.
AB  - The spatiotemporal expression patterns of the chemorepulsive EphA receptors,
      EphA4 and EphA7, and three ephrins-A2, A4 and A5, were examined in the developing
      rat primary olfactory system. Unlike the visual system that has simple and stable
      gradients of Ephs and ephrins, the olfactory system demonstrates complex
      spatiotemporal expression patterns of these molecules. Using
      immunohistochemistry, we demonstrate that expression of these molecules is
      dynamic and tightly regulated both within and between different cell types. We
      reveal restricted targeting of these proteins within subcellular compartments of
      some neurons. EphA4, ephrin-A2 and ephrin-A5 were expressed by primary olfactory
      axons during the embryonic formation of the olfactory nerve. There were no
      gradients in expression along the rostrocaudal or ventrodorsal axes in the nasal
      cavity and olfactory bulb. However, during the early neonatal period, axons
      expressing different levels of ephrin-A5 sorted out and terminated in a
      subpopulation of glomeruli that were mosaically dispersed throughout the bulb.
      The expression of EphA4 and ephrin-A2 was dramatically down-regulated on all
      axons during the early neonatal period of glomerular formation. The uniform co
      expression of receptors and ligands before glomerular formation suggests they
      play a generic role in axon-axon interactions in the olfactory nerve and nerve
      fibre layer. In contrast, loss of EphA4 from axons during glomerular formation
      may facilitate the interaction of ephrin-A5 with Eph receptors on target cells in
      the bulb. While EphA4, EphA5 and EphA7 are not mosaically expressed by bulbar
      neurons, other Eph receptors may have expression patterns complementary to the
      ephrin-A5-positive subpopulation of glomeruli.

PMID- 12234654
TI  - Lasting effects of adolescent nicotine exposure on the electroencephalogram,
      event related potentials, and locomotor activity in the rat.
AB  - Tobacco smoking initiated during adolescence is often associated with rapid onset
      of dependence and difficulty in maintaining abstinence. Animal models have
      demonstrated that adolescent nicotine exposure causes cell death and altered
      neurochemistry in the cortex and hippocampus; however, little is known about the
      neurophysiological consequences of adolescent nicotine exposure in the adult. The
      primary objective of this study was to assess the consequences of adolescent
      nicotine exposure on the adult electroencephalogram (EEG) and event-related
      potentials. Male Sprague-Dawley rats were administered nicotine (5.0 mg/kg per
      day) for 5 days between postnatal days 35 and 40 using transdermal nicotine
      patches. Following 6-7 weeks of nicotine withdrawal, EEG activity and event
      related potentials were assessed. Motor activity and sucrose preference were also
      examined during the nicotine withdrawal period. Additionally, a set of rats was
      exposed to multiple doses of nicotine for a single day to assess nicotine and
      cotinine blood levels. Transdermal nicotine produced nicotine (88+/-21.5 ng/ml)
      and cotinine (647.6+/-123.2 ng/ml) levels comparable to those previously
      reported. Reduced motor activity, decreased 1-4 Hz power in the cortical
      electroencephalogram, and increased cortical N1 amplitude were observed in
      nicotine-exposed rats compared to controls. These data demonstrate that
      transdermal nicotine patches provide an effective and non-invasive nicotine
      delivery system for the adolescent rat. The combined neurophysiological and
      locomotor activity changes observed in nicotine-exposed rats demonstrate that
      adolescent nicotine exposure has lasting neurobehavioral consequences. These
      changes may be indicative of a lasting 'nicotine abstinence syndrome'
      characterized by increased arousal, anxiety, or emotionality.

PMID- 12234655
TI  - Cocaine differentially alters behavior and neurochemistry in periadolescent
      versus adult rats.
AB  - This study examined whether there are differences in the behavioral and
      neurochemical effects of cocaine in periadolescent rats compared to adult rats.
      Periadolescent (postnatal days 28-35) and adult rats were injected with cocaine
      or vehicle for 7 days. Ten days later (day 17), rats either were challenged with
      cocaine, or dopamine transporter and receptor and serotonin transporter binding
      were examined. Adult rats became sensitized to the locomotor-activating effects
      of cocaine and there were increases in dopamine transporter density in the
      caudate putamen compared to vehicle-treated adult rats. In addition, serotonin
      transporter densities were increased in the ventromedial caudate putamen, nucleus
      accumbens shell, and the olfactory tubercle in cocaine-treated adult rats
      compared to vehicle-treated adult rats. In contrast, periadolescent rats did not
      show sensitization to cocaine and there was no effect of cocaine on either
      dopamine or serotonin transporter densities. These findings suggest that there
      are different neurochemical and behavioral adaptations to repeated cocaine
      administration in periadolescent versus adult rats.

PMID- 12234656
TI  - Reduction of early thalamic input alters adult corticocortical connectivity.
AB  - The functional specificity of mammalian isocortex requires that precise
      connections be established between cortical areas and their targets. While recent
      studies of cortical development have focused on intrinsic specification, the role
      of extrinsic factors has received considerably less attention. In the present
      study, we examined how early removal of thalamic input affects the development of
      visual corticocortical connections. Hamster pups received ablations of visual
      thalamic nuclei on the day of birth. At 30 days of age, an injection of
      horseradish peroxidase (HRP) was placed into the area of cortex deafferented by
      the early thalamic ablation to retrogradely label adult corticocortical
      connections. Ablated animals displayed a significant increase in the number of
      corticocortical connections compared to control animals. The increased
      connectivity in ablated animals was primarily due to a significant increase in
      the number of corticocortical projections arising from non-visual areas. These
      results demonstrate that an intact thalamocortical projection is necessary for
      the development of normal cortical connectivity.

PMID- 12234657
TI  - Deficiency of neuronal nitric oxide synthase (nNOS) worsens alcohol-induced
      microencephaly and neuronal loss in developing mice.
AB  - Previous work conducted in vitro suggests that nitric oxide (NO) protects
      developing neurons against the toxic effects of alcohol. We tested the hypothesis
      that neonatal mice carrying a null mutation for neuronal nitric oxide synthase
      (nNOS), the enzyme which synthesizes NO in neurons, have increased vulnerability
      to alcohol-induced microencephaly and neuronal loss. Wild-type mice and mutant
      (nNOS(-/-)) mice received a single intraperitoneal injection of ethanol (0.0,
      2.2, 3.3, or 4.4 g/kg) daily over postnatal days (PD) 4-9 and were sacrificed on
      PD 10. Peak blood alcohol concentrations were approximately 170, 280, and 385
      mg/dl for the 2.2, 3.3 and 4.4 g/kg/day treatment groups, respectively, and did
      not differ significantly between wild-type and nNOS(-/-) strains. Exposure to
      alcohol induced dose-dependent reductions in total brain weight, forebrain weight
      and cerebellum weight in both strains of mice. However, the reductions in brain
      weight were significantly more severe in the nNOS(-/-) mice than in wild type.
      Quantification of cerebellar neurons revealed that alcohol-induced losses of
      Purkinje cells and granule cells were both significantly greater in the nNOS(-/-)
      mice than in wild type. The increased vulnerability of nNOS-deficient neurons to
      alcohol-induced cell death was confirmed in vitro. Cerebellar granule cell
      cultures derived from nNOS(-/-) and wild-type mice were exposed for 24 h to 0,
      100, 200 or 400 mg/dl ethanol. At each alcohol concentration, the nNOS(-/-)
      neurons had a significantly greater cell loss than did the wild-type neurons. The
      results demonstrate that deficiency of nNOS decreases the ability of developing
      neurons to survive the toxic effects of alcohol. Because NO upregulates
      intracellular cGMP, which can activate cGMP-dependent protein kinase (PKG), we
      hypothesize that the NO-cGMP-PKG pathway has a neuroprotective role against
      alcohol toxicity within the developing brain.

PMID- 12234658
TI  - Developmentally regulated expression of CaMKII and iGluRs in the rat retina.
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) and the ionotropic
      glutamate receptors (iGluRs) have been shown to be pivotal in the maturation of
      synapses during development of the central nervous system. The purpose of the
      current study was to assay the expression profiles of these molecules during the
      development of the rat retina. The mRNA levels of CaMKII were determined by the
      semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR)
      method. The protein levels of CaMKII were assayed in slot blots. The CaMKII
      enzyme activity was also measured. In addition, the protein levels of iGluRs in a
      retinal membrane-enriched fraction were evaluated in Western blots. The results
      show that the levels of CaMKII (mRNA, protein, and activity) and distinct
      subunits of iGluR proteins increased during the first 2 weeks after birth. The
      highest level of CaMKII was reached during the second postnatal week, coincident
      with the peak of synaptogenesis in the inner plexiform layer of the rat retina.
      The expressions of NMDAR-NR1 and -NR2A were relatively low in the first postnatal
      week but rose quickly thereafter. However, NMDAR-NR2B was relatively high at
      postnatal day 5 (P5) and increased steadily during the postnatal period. Thus,
      the subunit compositional profile of the retinal NMDARs was altered during
      retinal maturation. The developmental pattern of AMPAR-GluR1 was similar to that
      of NMDAR-NR2B, with high expression at P5, and modest increases thereafter. The
      patterns of CaMKII and NR1/NR2A were better correlated than were CaMKII and NR2B,
      or CaMKII and GluR1. The temporal differences in subunit expression of these
      synaptically relevant molecules suggest that they play distinct roles during the
      development of the retina.

PMID- 12234659
TI  - Developmental expression of nitric oxide/cyclic GMP signaling pathways in the
      brain of the embryonic grasshopper.
AB  - Biochemical, cytochemical, and physiological investigations have demonstrated the
      presence of the nitric oxide/cyclic GMP signaling system in the brain of the
      adult locust, Schistocerca gregaria. Here, we characterize nitric oxide (NO)
      releasing neurons and neurons that synthesize cyclic GMP (cGMP) in response to a
      NO stimulus in the brain of the embryonic grasshopper. Using NADPH-diaphorase
      histochemistry to detect NO synthesizing cells we describe the appearance of
      several individually identifiable neurons. At embryonic stage 50% four NADPH
      diaphorase positive neurons can be detected in each brain hemisphere. In addition
      to the labeling of differentiating neurons, NADPH-diaphorase staining appears
      also in distinct proliferative cell clusters. At embryonic stage 70% the general
      organization of NADPH-diaphorase activity starts to resemble the adult brain. The
      immunocytochemical detection of NO-induced accumulation of cGMP starts at
      embryonic stage 45% resulting in the staining of large neuronal populations in
      all brain areas. During embryonic stages 50-70%, the number of cGMP
      immunoreactive cells increases from 200 to several hundred in each brain
      hemisphere. Since all NADPH-diaphorase positive local interneurons of the adult
      antennal lobe express GABA-immunoreactivity, we also report on the earliest
      appearance of GABA-immunoreactivity in the embryonic antennal lobe. Thus, we
      present a first developmental investigation of nitrergic and GABAergic
      transmitter phenotypes in the brain of the embryonic grasshopper.

PMID- 12234660
TI  - Developmental expression of serum response factor in the rat central nervous
      system.
AB  - Serum response factor (SRF), a transcription factor known to be essential for
      early embryonic development as well as post-natal regulation of both cellular
      proliferation and myogenic differentiation, is expressed broadly in neurons
      within the adult mammalian central nervous system (CNS). The function of SRF
      within the developing CNS is not well established, but it is likely to play an
      important role in neuraxial development and neuronal function, since many of its
      known target genes (e.g., c-fos) and transcriptional partners (e.g., Elk-1) are
      also highly expressed in neurons. Immunohistochemical survey of the post-natal
      developing rat brain revealed a progressive increase in SRF immunoreactivity in
      neurons of the cerebral and cerebellar cortices, and in selective subcortical
      regions from birth (P0) through post-natal day 28 (P28). SRF immunoreactivity
      stabilized from P28 into adulthood. A few loci, such as the nucleus of cranial
      nerve VII, showed the reverse expression pattern (strong immunoreactivity at P0
      P7, declining by P28). The developmental expression pattern of SRF overlaps
      significantly with that of myotonic dystrophy protein kinase, a potential
      upstream regulator, and of the LIM-only genes Lmo1, Lmo2 and Lmo3, whose products
      belong to a family of proteins known to be strong positive regulators of SRF's
      transcriptional activity. These data suggest that SRF has a significant function
      in the early post-natal development of the CNS.

PMID- 12234661
TI  - Inhibitory control of the urinary bladder in the neonatal rat in vitro spinal
      cord-bladder preparation.
AB  - Urinary bladder activity of the neonatal rat is tonically inhibited by neural
      input from the spinal cord passing through axons in the pelvic nerve. The present
      study was undertaken to examine the organization of this inhibitory mechanism
      using in vitro spinal cord-bladder preparations of neonatal rats in which the
      lumbosacral dorsal roots (DRs) or ventral roots (VRs) were transected.
      Isovolumetric bladder contractions occurring spontaneously or induced by
      electrical stimulation of the bladder wall (ES-BW) were measured. In DR
      transected (DRT) preparations, removal of the spinal cord significantly enhanced
      (50-59%) the amplitude of spontaneous and ES-BW-evoked bladder contractions;
      whereas in VR transected (VRT) preparations removal of the spinal cord produced
      only a small enhancement (6.7-12%). However, in VRT preparations, electrical
      stimulation of the dorsal roots reduced the amplitude of spontaneous
      contractions, an effect blocked by a nicotinic ganglionic blocking agent,
      hexamethonium. In DRT preparations, MK-801 enhanced the amplitude of spontaneous
      and ES-BW-evoked contractions. These results demonstrate that bladder activity of
      the neonatal rat is tonically inhibited by input from the lumbosacral spinal cord
      via parasympathetic pathways in the pelvic nerve. The inhibitory outflow is not
      dependent upon afferent input to the cord but is facilitated by NMDA
      glutamatergic transmission in the spinal cord. Antidromic activation of afferent
      axons also appears to induce inhibition in the bladder via a mechanism involving
      nicotinic cholinergic receptors. These findings suggest that spinal and
      peripheral inhibitory mechanisms may play an important role in controlling
      voiding in the neonatal rat.

PMID- 12234662
TI  - Integration and diversity of the regulatory network composed of Maf and CNC
      families of transcription factors.
AB  - Recent progress in the analysis of transcriptional regulation has revealed the
      presence of an exquisite functional network comprising the Maf and Cap 'n' collar
      (CNC) families of regulatory proteins, many of which have been isolated. Among
      Maf factors, large Maf proteins are important in the regulation of embryonic
      development and cell differentiation, whereas small Maf proteins serve as
      obligatory heterodimeric partner molecules for members of the CNC family. Both
      Maf homodimers and CNC-small Maf heterodimers bind to the Maf recognition element
      (MARE). Since the MARE contains a consensus TRE sequence recognized by AP-1, Jun
      and Fos family members may act to compete or interfere with the function of CNC
      small Maf heterodimers. Overall then, the quantitative balance of transcription
      factors interacting with the MARE determines its transcriptional activity. Many
      putative MARE-dependent target genes such as those induced by antioxidants and
      oxidative stress are under concerted regulation by the CNC family member Nrf2, as
      clearly proven by mouse germline mutagenesis. Since these genes represent a vital
      aspect of the cellular defense mechanism against oxidative stress, Nrf2-null
      mutant mice are highly sensitive to xenobiotic and oxidative insults. Deciphering
      the molecular basis of the regulatory network composed of Maf and CNC families of
      transcription factors will undoubtedly lead to a new paradigm for the cooperative
      function of transcription factors.

PMID- 12234663
TI  - Cloning and characterization of human and mouse SNRK sucrose non-fermenting
      protein (SNF-1)-related kinases.
AB  - We previously isolated, from the earliest population of CD34+ hematopoietic
      progenitors that form in the aorta of the human embryo, a partial DNA
      complementary to RNA (cDNA) sequence that was later identified as the human
      homologue of rat sucrose non-fermenting protein (SNF-1) related kinase (rSNRK), a
      novel SNF-1-related kinase previously characterized in the rat. In the present
      study we report the cloning of the complete human SNF-1 related kinase (hSNRK)
      cDNA and show that the gene spans 39.8 kb at region 3p21 and contains six exons.
      Recombinant expression of the hSNRK coding sequence in Escherichia coli led to
      the production of a functional protein kinase of 85 kDa. Reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis of hSNRK expression in fetal CD34+
      hematopoietic progenitors revealed its continuous expression throughout human
      development with higher levels in highly dividing CD34+ CD38+ cells compared to
      quiescent CD34+ CD38- cells. This observation, together with the expression of
      hSNRK in numerous human leukemic cell lines, may reflect an implication of hSNRK
      protein in hematopoietic cell proliferation or differentiation. In the mouse, the
      SNRK cDNA is 4.6-kb-long and encodes a protein of 748 amino acids with a
      predicted molecular mass of 81,930 Da. The proteins from human, rat and mouse are
      strongly conserved and are characterized by the presence of a serine/threonine
      kinase catalytic domain, a bipartite nuclear targeting signal and an ubiquitin
      associated domain. In situ hybridization and RT-PCR analysis of the pattern of
      mSNRK expression in the mouse reveals that it is temporally and spatially
      regulated during embryogenesis, and widespread expressed in adult tissues.

PMID- 12234664
TI  - A systematic investigation identifies a significant number of probable
      pseudogenes in the Escherichia coli genome.
AB  - Pseudogenes are open reading frames (ORFs) encoding dysfunctional proteins with
      high homology to known protein-coding genes. Although pseudogenes were reported
      to exist in the genomes of many eukaryotes and bacteria, no systematic search for
      pseudogenes in the Escherichia coli genome has been carried out. Genome
      comparisons of E. coli strains K-12 and O157 revealed that many protein-coding
      sequences have prematurely terminated orthologs encoding unstable proteins. To
      systematically screen for pseudogenes, we selected ORFs generated by premature
      termination of the orthologous protein-coding genes and subsequently excluded
      those possibly arising from sequence errors. Lastly we eliminated those with
      close homologs in this and other species, as these shortened ORFs may actually
      have functions. The process produced 95 and 101 pseudogene candidates in K-12 and
      O157, respectively. The assigned three-dimensional structures suggest that most
      of the encoded proteins cannot fold properly and thus are dysfunctional,
      indicating that they are probably pseudogenes. Therefore, the existence of a
      significant number of probable pseudogenes in E. coli is predicted, awaiting
      experimental verification. Most of them were found to be genes with paralogs or
      horizontally transferred genes or both. We suggest that pseudogenes constitute a
      small fraction of the genomes of free-living bacteria in general, reflecting the
      faster elimination than production of pseudogenes.

PMID- 12234665
TI  - Fugu and human sequence comparison identifies novel human genes and conserved non
      coding sequences.
AB  - The compact genome of the pufferfish, Fugu rubripes, has been proposed as a
      'reference' genome to aid in annotating and analysing the human genome. We have
      annotated and compared 85 kb of Fugu sequence containing 17 genes with its
      homologous loci in the human draft genome and identified three 'novel' human
      genes that were missed or incompletely predicted by the previous gene prediction
      methods. Two of the novel genes contain zinc finger domains and are designated
      ZNF366 and ZNF367. They map to human chromosomes 5q13.2 and 9q22.32,
      respectively. The third novel gene, designated C9orf21, maps to chromosome
      9q22.32. This gene is unique to vertebrates, and the protein encoded by it does
      not contain any known domains. We could not find human homologs for two Fugu
      genes, a novel chemokine gene and a kinase gene. These genes are either specific
      to teleosts or lost in the human lineage. The Fugu-human comparison identified
      several conserved non-coding sequences in the promoter and intronic regions.
      These sequences, conserved during 450 million years of vertebrate evolution, are
      likely to be involved in gene regulation. The 85 kb Fugu locus is dispersed over
      four human loci, occupying about 1.5 Mb. Contiguity is conserved in the human
      genome between six out of 16 Fugu gene pairs. These contiguous chromosomal
      segments should share a common evolutionary history dating back to the common
      ancestor of mammals and teleosts. We propose contiguity as strong evidence to
      identify orthologous genes in distant organisms. This study confirms the utility
      of the Fugu as a supplementary tool to uncover and confirm novel genes and
      putative gene regulatory regions in the human genome.

PMID- 12234667
TI  - Structure and spatio temporal expression of the full length DNA complementary to
      RNA coding for alpha2 type I collagen of zebrafish.
AB  - Twenty distinct genetic types of collagen have been identified up to now. Their
      structure and function are not completely elucidated. We have chosen zebrafish as
      a model to bring information about the role of collagen during embryogenesis. In
      the present study, we isolated four overlapping DNA complementary to RNA clones
      covering the 4879 nucleotides of a zebrafish messenger RNA (mRNA) encoding a
      fibrillar procollagen chain. The comparison of its primary structure with known
      other vertebrate collagens allowed to conclude that it encodes collagen pro
      alpha2(I) chain. The 5' untranslated region showed a typical stem-loop structure
      with three ATG codons which is found in mammals types I and III collagen chains
      (but not in type II), which are expressed in the same tissues. This suggests that
      the supposed regulatory role of the stem loop structure could be tissue specific.
      The comparison of the Gly-Gly doublets found along the helical domain of several
      species allowed to speculate that the Gly-Gly repeats could be a poikilotherm
      feature. Expression of pro-alpha2(I) was examined during zebrafish development by
      reverse transcriptase-polymerase chain reaction and in situ hybridization on
      whole embryo and tissue section. Col1a2 was expressed as early as stage10 h post
      fertilization (hpf) and two peaks of expression were observed at 20 and 48 hpf.
      alpha2 mRNAs, whose presence suggests a collagen synthesis, were detected
      principally in the superficial cell layers surrounding 20-72 hpf embryos which
      are characterized by an acellular collagen stratum. At 26-30 days, fibroblasts
      invade the dermis and take over from the epithelial cells to synthesize collagen.
      This suggests a fine regulation of collagen synthesis in these cells that remains
      to be elucidated. alpha2 mRNA were also detected in other tissues such as the
      tail fin primordium and the notochord primordium suggesting a participation of
      type I collagen in a pathway for notochord and tail formation.

PMID- 12234668
TI  - Temporal expression profile of late gene expression factor 4 from Bombyx mori
      nucleopolyhedrovirus.
AB  - Temporal expression profile of lef4, the gene encoding late gene expression
      factor 4 (LEF4) from the baculovirus, Bombyx mori nucleopolyhedrovirus (BmNPV),
      has been analysed. lef4 behaved like an early gene and the transcripts were
      detectable from 6 h post infection (hpi) which reached maximal levels by 18-24
      hpi, and declined considerably at later times. The LEF4 open reading frame was
      bacterially expressed as a glutathione S-transferase (GST) fusion protein which
      was solubilized from the inclusion bodies and purified by adsorption to the
      affinity matrix, GST-Sepharose. Using polyclonal antibodies raised against the
      bacterially expressed protein, the temporal profile of LEF4 synthesis in BmNPV
      infected BmN cells was analysed. The LEF4 protein levels were also higher at 24
      hpi compared to 12 or 36 hpi, correlating with the RNA patterns. The protein was
      predominantly localized to the nucleus of the infected BmN cell and only a small
      portion was present in the cytosolic fraction. Preliminary studies with antisense
      lef4 expression revealed substantial reduction in expression from the viral
      polyhedrin promoter without significantly affecting the viral DNA replication.

PMID- 12234669
TI  - Genetic evidence for a dystrophin-glycoprotein complex (DGC) in Caenorhabditis
      elegans.
AB  - Dystrophin is the product of the gene mutated in Duchenne muscular dystrophy
      (DMD). Neither the function of dystrophin nor the physiopathology of the disease
      have been clearly established so far. In mammals, the dystrophin-glycoprotein
      complex (DGC) includes dystrophin, as well as transmembrane and cytoplasmic
      proteins. Since Caenorhabditis elegans possesses a dystrophin-like gene (dys-1),
      we investigated whether homologues of the DGC members could also be found in the
      C. elegans genome. Conserved homologues were found for dystroglycan, delta/gamma
      sarcoglycan and syntrophin. Divergent but related proteins were found for alpha-
      and beta-sarcoglycans. No sarcospan counterpart was found. The expression of the
      conserved homologues was inactivated using the RNA interference technique.
      Phenotypes similar to that of dys-1 were obtained, both in the wild-type
      background and in combination with other mutations. These results strongly
      suggest that a protein complex comprising functional analogies with the DGC
      exists in C. elegans.

PMID- 12234670
TI  - A novel Syk-family tyrosine kinase from Schistosoma mansoni which is
      preferentially transcribed in reproductive organs.
AB  - The complete coding deoxyribonucleic acid for a novel tyrosine kinase (TK) of the
      human parasite Schistosoma mansoni has been cloned and characterized. The
      molecule was designated TK4. The sequence predicts a translation product of about
      140 kDa containing two Src homology 2 domains and a tyrosine kinase domain. Data
      base analyses indicate that TK4 belongs to the Syk family of TKs which has not
      been identified in schistosomes or other Acoelomata yet. The presence of a member
      of the Syk family in this phylum supports previous findings demonstrating that TK
      subclasses were established early in evolution. Although Northern blot and
      reverse transcription polymerase chain reaction analyses show transcription of
      TK4 in larval stages and adult schistosomes of both genders, TK4 is more
      abundantly transcribed in males. In situ hybridization data demonstrate the
      gender-independent occurrence of TK4 transcripts in parenchymatic cells.
      Significant signals were detected in the oocytes of the female and in the
      spermatocytes of the male suggesting that TK4, among other functions, may play a
      role in germ cell development. This is an unexpected finding considering that Syk
      family TKs of invertebrates and vertebrates described so far are not involved in
      the differentiation of the gonads.

PMID- 12234671
TI  - Multiple splice variants of Par3 and of a novel related gene, Par3L, produce
      proteins with different binding properties.
AB  - The partitioning-defective 3 (par3) gene encodes a protein with three
      postsynaptic density90/DiscslargeA/ZO-1 (PDZ) domains that is required for cell
      polarity establishment in metazoans. Par3 is a component of a protein complex
      that can include Cdc42-GTP, Par6 and atypical protein kinase Cs (aPKCs). We now
      describe the identification of a related human gene, Par3L. Both Par3L and Par3
      are expressed as numerous alternatively spliced variants. Although Par3
      expression appears to be ubiquitous, that of Par3L is more restricted. Multiple
      variants are often expressed simultaneously within a specific cell type or
      tissue. Although all of the Par3L/Par3 isoforms can associate with tight
      junctions in epithelial cells, they show different binding properties. No Par3L
      isoforms and only a subset of Par3 isoforms detectably bind aPKCs. These data
      suggest that aPKC binding or phosphorylation is not required for targeting of
      Par3/Par3L to cell-cell contacts. Par3L isoforms also show differential binding
      to Par6. Despite these differences, the N-terminal region of Par3L, like that of
      Par3, can disrupt the formation of tight junctions when ectopically expressed in
      Madin-Darby canine kidney (MDCK) cells.

PMID- 12234672
TI  - Mouse cytosolic and mitochondrial deoxyribonucleotidases: cDNA cloning of the
      mitochondrial enzyme, gene structures, chromosomal mapping and comparison with
      the human orthologs.
AB  - Two of the five known mammalian 5'-nucleotidases show a preference for the
      dephosphorylation of deoxynucleoside-5'-phosphates. One is a cytoplasmic enzyme
      (dNT-1), the other occurs in mitochondria (dNT-2). The human mitochondrial
      enzyme, recently discovered and cloned by us, is encoded by a nuclear gene
      located on chromosome 17 p11.2 in the critical region deleted in the Smith
      Magenis syndrome (SMS), a genetic disease of unknown etiology. Looking for a
      model system to study the possible involvement of dNT-2 in the disease, we have
      cloned the cDNA of the mouse ortholog. The deduced protein sequence is 84%
      identical to the human ortholog, has a very basic NH(2)-terminus, a very high
      calculated probability of being imported into mitochondria and contains the
      DXDXT/V motif conserved among nucleotidases. Expression in Escherichia coli of
      the predicted processed form of the protein produced an active
      deoxyribonucleotidase. We also identified in genomic sequences present in the
      data base the structures of the murine genes for the cytosolic and mitochondrial
      deoxyribonucleotidases (Nt5c and Nt5m). PAC clones for the two loci were isolated
      from a library and used for chromosomal localization by fluorescent in situ
      hybridization. Both genes map on chromosome 11: Nt5c at 11E and Nt5m at 11B,
      demonstrating the presence of the dNT-2 locus in the mouse shaker-2 critical
      region, the murine counterpart of the human SMS region. We performed pair-wise
      dot-plot and PIP (percent identity plot) analyses of mouse and human
      deoxyribonucleotidase genes, and found a strong conservation that extends also to
      some intronic sequences of possible regulatory significance.

PMID- 12234673
TI  - Pika and vole mitochondrial genomes increase support for both rodent monophyly
      and glires.
AB  - Complete mitochondrial genomes are reported for a pika (Ochotona collaris) and a
      vole (Volemys kikuchii) then analysed together with 35 other mitochondrial
      genomes from mammals. With standard phylogenetic methods the pika joins with the
      other lagomorph (rabbit) and the vole with the other murid rodents (rat and
      mouse). In addition, with hedgehog excluded, the seven rodent genomes
      consistently form a homogeneous group in the unrooted placental tree. Except for
      uncertainty of the position of tree shrew, the clade Glires (monophyletic rodents
      plus lagomorphs) is consistently found. The unrooted tree obtained by ProtML
      (Protein Maximum Likelihood, a program in MOLPHY) is compatible with a
      reclassification of mammals [Syst. Biol. 48, 1-5 (1999)] which is also supported
      by other recent studies. However, when this tree is rooted with marsupials plus
      platypus, the outgroup often joins the lineage leading to the three murid
      rodents, so the rodents are no longer monophyletic. Apart from misplacing the
      root, the presence of the outgroups also distorts other parts of the unrooted
      tree. Either constraining the tree to maintain rodents monophyletic, or omitting
      murids, maintains the ingroup tree and sees the outgroup join on the edge to
      Xenarthra, to Afrotheria, or to these two groups together. This emphasises the
      importance of carrying out both an unrooted and a rooted analysis. It is known
      from cancer research that murid rodents have reduced activity in some DNA repair
      mechanisms and this alters their substitution pattern - this may be the case for
      mitochnodrial DNA as well. Comparing nucleotide compositions may identify taxa
      that differ in aspects of their DNA repair mechanisms.

PMID- 12234666
TI  - Expressed sequence tag analysis of expression profiles of zebrafish testis and
      ovary.
AB  - In the present study, two gonad cDNA libraries from zebrafish testes and ovaries
      were constructed and a total of 1025 expressed sequence tag (EST) clones were
      generated from the two libraries: 501 from the testis library and 524 from the
      ovary library. A total of 641 of the EST clones were identified to share
      significant sequence identity with known sequences in GenBank, representing at
      least 478 different zebrafish genes. In order to understand the molecular
      compositions of the two gonad organs, the expression profiles of the identified
      clones in these two gonad cDNA libraries were analyzed. Both gonad libraries have
      a higher portion of clones for nuclear proteins and a lower portion for proteins
      in translational machinery, cytoskeleton and mitochondria than our previously
      characterized whole-adult cDNA library. Most abundant cDNA clones in the two
      gonad libraries were identified and over 10% of ovary clones were found to encode
      egg membrane proteins (zona pellucida or ZP proteins). Furthermore, the testis
      library showed a more even distribution of cDNA clones with relatively fewer
      abundant clones that tend to contribute redundant clones in EST projects; thus,
      the testis library can supply more unique and novel cDNA sequences in a zebrafish
      EST project. Another aim of this study is to identify cDNA clones that can be
      used as molecular markers for the analysis of the gonad development in zebrafish.
      Eleven potential clones were selected to analyze their expression patterns by
      Northern blot hybridization. Most of them showed a specific or predominant
      expression in the expected testis or ovary tissue. At last, four of the clones
      were found, by section in situ hybridization, to be expressed specifically in the
      germ cells of the testis or ovary and thus they are suitable molecular markers
      for analyses of spermatogenesis and oogenesis.

PMID- 12234674
TI  - FOXD4a and FOXD4b, two new winged helix transcription factors, are expressed in
      human leukemia cell lines.
AB  - Winged helix factors are important regulators of embryonal development and tissue
      differentiation. They are also involved in translocations found in acute
      leukemias and solid tumors. We have detected transcripts from five known and four
      novel winged helix genes in leukemia cell lines and CD34(+) blood progenitor
      cells by reverse trancription-polymerase chain reaction with degenerate primers
      on the highly conserved DNA binding domain. The genomic clones coding for two new
      winged helix proteins, FOXD4a and FOXD4b were isolated by high-stringency
      hybridization of a human phage library. FOXD4a and FOXD4b are encoded by a 1319
      and 1250 bp single exon coding for a winged helix DNA binding domain, an amino
      terminal acidic region and a carboxy-terminal proline- and alanine-rich region
      which correspond to putative transcriptional regulatory motifs. TATA box, CCAAT
      box, and transcription factor binding motifs have been identified in the 5'
      region of the genes. In addition, foxD4a and foxD4b cDNA has been isolated from
      NB-4 mRNA. The fox genes are transcribed in a tissue-restricted pattern in adult
      and fetal human tissues. FoxD4a and foxD4b mRNA was expressed in the leukemia
      cell lines KG-1, Kasumi, NB-4, HL-60, U937, THP-1, HEL, U266, Jurkat, and Raji.
      It has already been shown that winged helix factors are also involved in
      carcinogenesis. Based upon these studies, our results suggest that FOXD4a and
      FOXD4b may play a role in leukemogenesis.

PMID- 12234675
TI  - SDR-O: an orphan short-chain dehydrogenase/reductase localized at mouse
      chromosome 10/human chromosome 12.
AB  - We report cloning a cDNA that encodes a novel short-chain
      dehydrogenase/reductase, SDR-O, conserved in mouse, human and rat. Human and
      mouse liver express SDR-O (short-chain dehydrogenase/reductase-orphan) mRNA
      intensely. The mouse embryo expresses SDR-O mRNA as early as day seven. Human SDR
      O localizes on chromosome 12; mouse SDR-O localizes on chromosome 10 with CRAD1,
      CRAD2 and RDH4. SDR-O shares highest amino acid similarity with rat RoDH1 and
      mouse RDH1 (69-70%), but does not have the retinol and 3alpha-hydroxysteroid
      dehydrogenase activity of either, nor is it active as a 17beta- or 11beta
      hydroxysteroid dehydrogenase. Short-chain dehydrogenase/reductases catalyse the
      metabolism of ligands that bind with nuclear receptors: the occurrence of
      'orphan' nuclear receptors may imply existence of 'orphan' SDR, suggesting that
      SDR-O may catalyse the metabolism of another class of nuclear receptor ligand.
      Alternatively, SDR-O may not have a catalytic function, but may regulate
      metabolism by binding substrates/products and/or by serving as a regulatory
      factor.

PMID- 12234676
TI  - Organization, sequence, and phylogenetic analysis of the ribosomal protein S3
      gene from Drosophila virilis.
AB  - Ribosomal protein S3 (RPS3) is a multifunctional ribosomal protein: it is a
      structural and functional component of the ribosome, and also a DNA repair enzyme
      involved in the DNA base excision repair pathway. Here we cloned and
      characterized the genomic organization of the ribosomal protein S3 gene (RpS3)
      homolog in Drosophila virilis. We then compared gene structure and protein
      sequences of RpS3 from vertebrates, invertebrates, and plants. These comparisons
      revealed that RpS3 genes from plants to mammals have highly conserved coding and
      amino acid sequences, and also protein size. Further comparisons of the protein
      sequences show that important domains are well conserved in both localization and
      sequence. In contrast, comparison of gene size and organization reveals differing
      patterns and levels of conservation. Whereas invertebrate RpS3 genes are small in
      size and gene organization is variable (from zero to four introns), vertebrates
      have a considerably larger (but variable) gene size and a uniform gene
      organization. The larger gene size in vertebrates is due to increased number and
      expansion of introns. Although the plant RpS3 genes are relatively small (
      approximately 1.8 kb), their organization resembles that seen in vertebrates. The
      high conservation through different phyla may suggest that RPS3 might be under
      great functional constraints, both in its capacity as a component of the ribosome
      and as a component of a DNA repair system. Finally, electrophoretic mobility
      shift assays indicate that an upstream element binds a nuclear protein(s).

PMID- 12234677
TI  - Molecular cloning and expression of the cDNAs encoding luciferin-regenerating
      enzyme from Luciola cruciata and Luciola lateralis.
AB  - In the firefly light organ, oxyluciferin, a product of the light-emitting
      reaction of firefly luciferase, is thought to be converted into luciferin.
      Previously, we isolated the luciferin-regenerating enzyme (LRE) from Photinus
      pyralis. LRE plays an important role in the recycling of oxyluciferin into
      luciferin. We have cloned two cDNAs encoding LRE, G-LRE and H-LRE, from poly(A)+
      RNA of the lanterns of Luciola cruciata and Luciola lateralis, using reverse
      transcription-polymerase chain reaction, 5'-RACE (5'-rapid amplification of cDNA
      ends) and 3'-RACE. The putative translation products have molecular masses of
      33,804 and 34,285 Da, corresponding to 309 and 307 amino acids, respectively. The
      deduced amino acid sequence of G-LRE shows 57 and 56% identity with H-LRE and A
      LRE (P. pyralis), respectively. LRE (G-LRE, H-LRE, A-LRE) shows at most 39% amino
      acid sequence identity with insect anterior fat protein (AFP) and mammalian
      senescence marker protein-30 (SMP30). G-LRE and H-LRE were successfully expressed
      under the control of the lac promoter in Escherichia coli.

PMID- 12234678
TI  - Molecular cloning, characterization and mapping of the canine glucocorticoid
      receptor DNA binding factor 1 (GRLF1).
AB  - Progressive rod-cone degeneration (prcd) is an autosomal recessive retinal
      degeneration of dogs that maps to chromosome 9 (CFA9). Positional cloning and
      candidate gene approaches are presently used to identify the disease-causing
      gene. To complement these strategies and identify novel candidate genes, we have
      used a subtraction approach to detect modified gene expression caused by prcd
      that may be causally associated with the disease, or, alternatively, be involved
      in the molecular mechanisms leading to the disease phenotype. With this technique
      we characterized a 4503 nucleotide open reading frame (ORF) within a 5.6 kb cDNA
      that predicts a protein of 1500 amino acids. The gene shows about 90% homology to
      the human and rat glucocorticoid receptor DNA binding factor 1 (GRLF1) gene, also
      known as p190-A. The transcript was detected in several tissues, including
      retina, and the protein was localized to the photoreceptor cell layer. The canine
      GRLF1 maps near the telomere of CFA1 close to CRX, a region synteny to human
      chromosome 19q13 (HSA19q13). Based on its chromosomal location, GRLF1 has been
      excluded as a candidate gene for prcd. Northern blot analysis also failed to
      prove down-regulation of the gene in early stages of disease in six different non
      allelic canine retinal degenerations. However, we were able to show that in
      advanced stages of prcd, GRLF1 is expressed in remaining photoreceptor cells,
      thus, providing a challenging task to uncover the gene's exact function in the
      retina and degenerative processes.

PMID- 12234680
TI  - Identification and characterization of a novel U14 small nucleolar RNA gene
      cluster in Oryza sativa.
AB  - Small nucleolar RNAs (snoRNAs) are required for ribose 2'-O-methylation of
      eukaryotic ribosomal RNA. Through computer search in international rice genome
      database, a novel U14 snoRNA gene cluster, consisting of two U14 snoRNA gene
      candidates, was found on rice chromosome II. They both have box C/D sequences and
      a 14 nucleotides (nt)-long complementarity to rice 18S ribosomal RNA (rRNA).
      Functional analysis of this gene cluster indicated that both were transcribed in
      vivo and might guide the methylations of C418 in rice 18S rRNA. By using primer
      extension, 5' and 3' rapid amplification of cDNA ends, the 5' and 3' ends of two
      snoRNAs were determined. The 52 nt long intergenic spacer of the gene cluster is
      rich in uridine. The absence of a conserved promoter element in this spacer, the
      proximity of the genes and the detection of transcripts containing linked U14
      snoRNAs by reverse transcript polymerase chain reaction suggest that the rice U14
      snoRNAs encoded in the cluster are transcribed as a polycistron under an upstream
      promoter, and individual U14 snoRNAs are released after processing of the
      precursor RNAs.

PMID- 12234679
TI  - G350 of Escherichia coli RNase P RNA contributes to Mg2+ binding near the active
      site of the enzyme.
AB  - G350 of Escherichia coli RNase P RNA is a highly conserved residue among all
      bacteria and lies near the known magnesium binding site for the RNase P ribozyme,
      helix P4. Mutations at G350 have a dramatic effect on substrate cleavage activity
      for both RNA alone and holoenzyme; the G350C mutation has the most severe
      phenotype. The G350C mutation also inhibits growth of cells that express the
      mutant RNA in vivo under conditions of magnesium starvation. The results suggest
      that G350 contributes to Mg(2+) binding at helix P4 of RNase P RNA.

PMID- 12234681
TI  - An improved general approach for cloning and characterizing telomeres: the
      protozoan parasite Trypanosoma cruzi as model organism.
AB  - We here describe a general strategy for cloning and characterizing telomeric and
      sub-telomeric regions of the human protozoan parasite Trypanosoma cruzi. The use
      of a bacterial artificial chromosome vector and a telomeric adaptor produced
      stable telomeric recombinant clones with inserts ranging from 5 to 25 kb.
      Analysis of these recombinants provided unique landmarks for chromosomal mapping
      and sequencing and enabled us to derive a more accurate picture of T. cruzi
      telomeric organization.

PMID- 12234682
TI  - A unique pause pattern during telomere addition by the error-prone telomerase
      from the ciliate Paramecium tetraurelia.
AB  - Telomeric DNA - the short, tandemly repeated sequences at the ends of chromosomes
      - is synthesized by telomerase, a ribonucleoprotein enzyme that copies a specific
      template sequence within its integral RNA moiety. The error-prone telomerase from
      the ciliate Paramecium tetraurelia stereotypically misincorporates TTP at
      telomerase RNA templating nucleotide C52, accounting for the 30% TTTGGG repeats
      randomly distributed in wild-type telomeres. Paramecium tetraurelia telomerase
      has been isolated from macronuclear extracts and characterized with respect to
      the extension of telomeric primers in vitro. Unlike telomerase activities from
      other species, the predominant pause during telomeric repeat synthesis by P.
      tetraurelia telomerase does not occur at the 5' end of the templating domain
      (templating nucleotide C49). Instead, the pause by P. tetraurelia telomerase is
      at templating nucleotide C53, immediately prior to incorporation of dGTP (or TTP)
      at C52. The configuration of the catalytic site at this template position during
      telomere synthesis is most likely responsible for the high incidence of
      misincorporation of TTP at C52. The gene for the P. tetraurelia telomerase
      catalytic subunit, telomerase reverse transcriptase (TERT), has been cloned and
      sequenced. A comparative analysis of the P. tetraurelia TERT with homologs from
      other species, including that from another Paramecium species that does not make
      a high percentage of misincorporation errors, has been initiated. This study may
      delineate those TERT structural elements that contribute to telomerase fidelity.

PMID- 12234683
TI  - The genomic organization, promoter position and expression profile of the mouse
      MRG15 gene.
AB  - MORF4 (mortality factor on chromosome 4) and the novel related MRG (MORF4-related
      gene) gene family were identified when MORF4 was shown to induce senescence in a
      subset of tumor cell lines. The gene on chromosome 15 (MRG15) has high similarity
      to Drosophila MSL3, which is a component of the dosage compensation complex.
      MRG15 also has a chromodomain and may therefore function as a chromatin
      remodeling factor in a complex(es) involving a histone acetyltransferase, similar
      to MSL3. To complement our studies on human MRG15, we cloned and characterized
      the mouse MRG15 gene. Mouse MRG15 is expressed ubiquitously in adult tissues and
      at various embryonic stages, and expression in adult testis is higher than in
      other tissues. MRG15-b, which is an alternatively spliced form of MRG15-a and has
      a 39-amino-acid insertion in the chromodomain, is also expressed in all mouse
      tissues examined and localizes to the nucleus of cells. It is possible that MRG15
      b may lack the function of the chromodomain because of the additional amino acids
      and could potentially be the equivalent of the human MORF4 in the mouse. The
      mouse MRG15 gene is composed of twelve exons and spans over 24 kb DNA. Using
      luciferase constructs we have determined that there is a functional promoter
      sequence 1.8 kb upstream of the ATG start codon. This region contains no TATA box
      but has GC-rich regions, consistent with the ubiquitous expression we have
      observed.

PMID- 12234684
TI  - The genomic sequence of the murine major vault protein and its promoter.
AB  - Vaults are ribonucleoproteins of unknown function, consisting of three different
      proteins and multiple copies of small untranslated RNA molecules. One of the
      protein subunits has been identified as TEP1, a protein that is also associated
      with the telomerase complex. Another protein appears to contain a functional PARP
      domain and is hence called VPARP. The third protein, major vault protein (MVP),
      is believed to make up 70% of the total mass of the vault complex and to be
      responsible for the typical barrel-shaped structure of vaults. We have isolated
      the murine MVP cDNA and compared the amino acid sequence with MVP from other
      species. Over 90% of sequence identity was found between mouse, human and rat,
      and a considerable degree of identity between mouse and MVPs from lower
      eukaryotes. We also found that the genomic structure of the murine MVP gene
      closely resembles the organization of the human MVP gene, both consisting of 15
      exons of which most have exactly the same size. Finally we have isolated a
      genomic region upstream (and partially overlapping) the first untranslated exon,
      that displayed promoter activity in a luciferase reporter assay. Furthermore, we
      showed that the sequences from the first exon together with the 5'-end of the
      first intron enhance the promoter activity, implying the presence of essential
      promoter elements in this region. Alignment of the murine promoter region with
      the homologous sequences of the human gene revealed an identity of 58%. The
      apparent presence of conserved promoter elements suggests a similar regulation of
      human and murine MVP expression.

PMID- 12234685
TI  - Molecular cloning and expression of gerbil granulocyte/macrophage colony
      stimulating factor.
AB  - Using a combination of cross species reverse transcriptase-polymerase chain
      reaction and 3' rapid amplification of cDNA ends techniques, we cloned the cDNA
      encoding gerbil granulocyte/macrophage colony-stimulating factor (GM-CSF). The
      open reading frame had 81% nucleotide identity with its mouse counterpart, while
      the mature protein had 80% homology with mature mouse GM-CSF. COS-7 cells
      transfected with gerbil GM-CSF cDNA secreted high levels of bioactive GM-CSF, as
      their supernatant stimulated gerbil bone-marrow cell proliferation and colony
      formation in semi-solid medium.

PMID- 12234686
TI  - Genomic structure and identification of a truncated variant message of the mouse
      estrogen receptor alpha gene.
AB  - Estrogen receptor alpha (ERalpha) is a ligand-dependent transcription factor that
      directs the transcription of a wide number of estrogen-regulated genes. ERalpha
      mediates the effects of 17-beta-estradiol in both males and females, and was the
      first estrogen receptor identified. Despite the cloning of the mouse ERalpha cDNA
      over 15 years ago, the precise genomic organization of the mouse ERalpha gene has
      not yet been elucidated. In order to determine the structure of this gene,
      overlapping BAC and P1 clones containing partial genomic sequences of the mouse
      ERalpha cDNA were obtained from a mouse ES cell genomic library. Using standard
      restriction fragment analysis followed by Southern blotting, the mouse ERalpha
      gene was determined to be greater than 220 kb in length. The introns vary widely
      in size, from 1.8 to 60 kb in length. Sequencing of intron-exon boundaries shows
      that these boundaries are highly conserved between the human and mouse ERalpha
      genes. Additionally, we have identified a splice variant message of mouse ERalpha
      arising from a failure to properly splice at the 3' end of exon 4; the resulting
      message is predicted to produce a protein lacking the ligand-binding domain.
      Variant message was detected by RT-PCR in several tissues, including uterus,
      ovary, mammary gland, placenta and testis.

PMID- 12234687
TI  - Characterization of IS999, an unstable genetic element in Mycobacterium avium.
AB  - An IS3-family insertion element, IS999, was identified in the opportunistic
      pathogen Mycobacterium avium. The 1347 bp element has 29 bp inverted repeats and
      two overlapping open reading frames coding for putative transposases. It was
      detected in the genomes of ten of 12 M. avium isolates examined. Copy numbers
      ranged from four to 16. IS999 is less stable than IS1245, the most commonly-used
      marker for typing M. avium isolates. Among 60 colonies picked from a single
      patient isolate, there were two distinct IS1245 restriction fragment length
      polymorphism banding patterns compared to eight distinct IS999 patterns (five in
      one IS1245 group and three in the other). In view of its instability, we asked
      whether transposition of IS999 might have phenotypic consequences. Nucleotide
      sequence analysis of insertion sites in four isolates revealed 16 putative
      structural genes that were variably disrupted by IS999. Insertions into hdhA, a
      gene that codes for a putative short chain alcohol dehydrogenase, were
      distributed non-randomly between colony type variants, consistent with phenotypic
      consequences that exert selective pressure. These observations illustrate the
      genetic heterogeneity that can exist within populations of M. avium that appear
      to be homogeneous by IS1245 analysis. IS999 may be a useful marker for tracking,
      at the sub-strain level, the rapid genetic drift that M. avium isolates undergo
      in nature and in the laboratory.

PMID- 12234688
TI  - Structural and functional characterization of the human PAX7 5'-flanking
      regulatory region.
AB  - The human PAX7 gene is a member of the paired box containing gene family of
      transcription factors implicated in development of the skeletal muscle of the
      trunk and limbs as well as elements of the central nervous system. To understand
      the molecular mechanisms involved in its expression, we have localized the
      transcription start sites in adult skeletal muscle and functionally characterized
      the 5'-flanking regulatory region responsible for PAX7 expression in this tissue.
      The major transcription start was identified 664 bp upstream from the ATG codon
      using primer extension and 5'-rapid amplification of cDNA ends (5'-RACE).
      Analysis of the 5'-flanking sequence revealed the absence of a TATA-box and the
      presence of an inverted CCAAT-box. Several consensus sites for common
      transcriptional regulators including Oct-1, NF1, AP2, AP4, CREB, Sp1, Nkx2.5, and
      MyoD are present in the promoter region. To determine the sites critical for the
      function of the PAX7 promoter, a series of deletion fragments of the 5'-flanking
      region were cloned adjacent to luciferase reporter gene and expressed in RD, Cos
      7 and JAR cell lines. The maximal promoter activity was achieved by a fragment
      extending from the position -403 to +373. No strong positive or negative
      regulatory elements were discovered by adding of further sequences (up to 2.97
      kb). A polymorphic (CCT)(n) repeat sequence was found 107 bp upstream of the
      transcription initiation site. PCR-based systematic screening for length
      variations in 227 unrelated individuals of a Caucasian population showed a
      bimodal distribution of three alleles containing 8, 10 or 11 repeat units. When
      different variants of this PAX7 gene-linked polymorphic region (PAX7-LPR) were
      fused to a luciferase reporter gene and transfected into RD cells, the variant
      with 11 repeat units revealed higher transcriptional efficiency compared to the 8
      or 10 repeat alleles.

PMID- 12234689
TI  - Cloning and characterization of the 5'-flanking region of the rat neuron-specific
      Class III beta-tubulin gene.
AB  - The promoter regions of several neuron-specific structural proteins (e.g.
      neurofilaments, peripherin, Talpha1-tubulin) have revealed potential regulatory
      elements that could contribute to the choice of a neuronal phenotype during
      development. We initiated study of the 5'-flanking region of the rat Class III
      neuron-specific beta-tubulin gene (betaIII-tubulin) because this gene is
      expressed at the time of terminal mitosis only in neurons and thus its promoter
      should be an excellent tool for studying neuron-specific gene expression during
      the transition from proliferative progenitor cell to early neuronal
      differentiation. We identified the minimal promoter region needed to drive
      expression of the betaIII-tubulin gene. This minimal region contains multiple
      putative binding sites for the transcription factors SP1 and AP2, as well as a
      central nervous system enhancer regulatory element and an E-box. A primer
      extension analysis identifies a single transcription start site. We highlight
      several putative regulatory elements that may modulate the expression of the
      betaIII-tubulin gene in a stage- and tissue-specific manner. In addition, we show
      that the first 490 bp of the promoter are sufficient to regulate betaIII-tubulin
      gene expression during neuronal differentiation of PCC7 cells.

PMID- 12234690
TI  - Ligand-dependent transcriptional enhancement by DNA curvature between two half
      motifs of the estrogen response element in the human estrogen receptor alpha
      gene.
AB  - We previously reported five DNA bend sites (ERB-4 to -1, and ERB+1) in the
      promoter region of the human estrogen receptor alpha (ERalpha) gene [FEBS Lett.
      444 (1999) 117]. One of these sites, ERB-2, was accompanied by two half motifs of
      the estrogen response element (ERE) and several short poly(dA)(.)poly(dT) tracts
      including an A(4) tract located next to a half ERE motif. This A(4) tract and the
      20 bp immediate flanking sequence containing a half ERE motif (T3B) exhibited DNA
      curvature. Transcription assays using luciferase as a reporter gene indicated
      that T3B sequence conferred positive estrogen responsiveness. Mutations
      introduced in this sequence indicated that both bendability and estrogen
      responsiveness were synergistically associated with the A(4) tract located next
      to the half ERE motif. This motif and a mutant sequence, GGTTA, had affinity for
      ERalpha protein, which seems to account for ERalpha protein binding to the region
      without an ERE motif. These findings suggest that some DNA curvature acts as a
      transcriptional modulator by modifying the state of ligand effects.

PMID- 12234691
TI  - Tumour necrosis is an independent prognostic marker in non-small cell lung
      cancer: correlation with biological variables.
AB  - BACKGROUND: Tumour necrosis (TN) is recognized to be a consequence of chronic
      cellular hypoxia. TN and hypoxia correlate with poor prognosis in solid tumours.
      METHODS: In a retrospective study the prognostic implications of the extent of TN
      was evaluated in non-small cell lung cancer (NSCLC) and correlated with
      clinicopathological variables and expression of epidermal growth factor receptor,
      Bcl-2, p53 and matrix metalloproteinase-9 (MMP-9). Tissue specimens from 178
      surgically resected cases of stage I-IIIA NSCLC with curative intent were
      studied. The specimens were routinely processed, formalin-fixed and paraffin
      embedded. TN was graded as extensive or either limited or absent by two
      independent observers; disagreements were resolved using a double-headed
      microscope. The degree of reproducibility was estimated by re-interpreting 40
      randomly selected cases after a 4 month interval. RESULTS: Reproducibility was
      attained in 36/40 cases, Kappa score = 0.8 P < 0.001. TN correlated with T-stage
      (P = 0.001), platelet count (P = 0.004) and p53 expression (P = 0.031). Near
      significant associations of TN with N-stage (P = 0.063) and MMP-9 expression (P =
      0.058) were seen. No association was found with angiogenesis (P = 0.98). On
      univariate (P = 0.0016) and multivariate analysis (P = 0.023) TN was prognostic.
      CONCLUSION: These results indicate that extensive TN reflects an aggressive
      tumour phenotype in NSCLC and may improve the predictive power of the TMN staging
      system. The lack of association between TN and angiogenesis may be important
      although these variables were not evaluated on serial sections.

PMID- 12234692
TI  - Genetic polymorphisms and lung cancer susceptibility: a review.
AB  - Lung cancer is a major cause of cancer-related death in the developed countries
      and the overall survival rate has still an extremely poor. Cigarette smoking is
      an established risk factor for lung cancer although a possible role for genetic
      susceptibility in the development of lung cancer has been inferred from familial
      clustering of the disease and segregation analyzes. Everyone may have a unique
      combination of polymorphic traits that modify genetic susceptibility and response
      to drugs, chemicals and carcinogens. Developments in molecular biology have led
      to growing interest in investigation of biological markers, which may increase
      predisposition to lung carcinogenesis. Therefore, the high-risk genotype of an
      individual could be determined easily. As there are the great number of
      carcinogen-activating and -detoxifying enzymes, the variation in their expression
      and the complexity of exposures to tobacco carcinogens, the existence of multiple
      alleles at loci of those enzymes may result in differential susceptibilities of
      individuals. This review summarize data addressing the relationships of lung
      cancer to markers of genetic susceptibility genes, including metabolic
      polymorphisms other than well-investigated cytochrome P450s or glutathione S
      transferases, DNA repair genes and the p53 tumor suppressor gene. Among genetic
      polymorphisms reviewed here, myeloperoxidase gene (a G to A mutation) and
      microsomal epoxide hydrolase exon 4 polymorphism (substitution of Arg for His)
      were significantly associated with lung cancer risk. As lung cancer is a
      multifactorial disease, an improved understanding of the interplay of
      environmental and genetic polymorphisms at multiple loci may help identify
      individuals who are at increased risk for lung cancer. Hopefully, in the future
      we will be able to screen for lung cancer susceptibility by using specific
      biomarkers.

PMID- 12234693
TI  - Characteristics of female smokers attending a lung cancer screening program: a
      pilot study with implications for program development.
AB  - Anticipating the development of lung cancer early detection programs, we examined
      the: (1) feasibility of a lung cancer early detection program; (2)
      characteristics of enrollees (e.g. motivation to quit smoking); (3) correlates of
      enrollee motivation to quit smoking; and (4) rates of smoking cessation following
      screening. Brief surveys were completed before and after screening, which
      involved sputum cytology, chest X-ray, bronchoscopy, spiral CT, and a meeting
      with an oncologist to discuss smoking cessation. Of the 168 eligible women who
      were heavy smokers recruited via newspaper and cancer center advertisements, 55
      agreed to undergo screening. Enrollees showed low-to-moderate levels of quit
      motivation and high levels of nicotine addiction; enrollees were interested in a
      range of smoking cessation treatments; 20% of enrollees exhibited clinical-levels
      of emotional distress; 64% of enrollees reported low levels of self-efficacy
      (i.e. self-confidence) to quit; 24% of enrollees reported low levels of quitting
      pros and 25% reported high levels of quitting cons; 31% of enrollees showed high
      levels of fatalistic beliefs about cancer; and all enrollees recognized their
      elevated lung cancer risk. Greater motivation to quit smoking was related to:
      greater age, lower nicotine addiction, fewer health symptoms, and higher quitting
      self-efficacy and quitting pros. Finally, 16% of enrollees quit smoking after
      screening. Overall, many women eligible for screening refused to undergo
      comprehensive screening that included bronchoscopy and spiral CT. Screening may
      represent an opportunity for quitting smoking, although more intensive smoking
      cessation interventions that target nicotine addiction and self-efficacy may be
      needed to maximize the health benefits of an early detection program.

PMID- 12234694
TI  - Molecular changes track recurrence and progression of bronchial precancerous
      lesions.
AB  - Diagnosis of lung cancer is reached when the disease had grown to advanced stages
      in its natural history. Thus, novel molecular markers for early detection and
      risk assessment are needed. Here we performed a longitudinal study of 20
      morphological lesions occurred in the bronchial tree of high-risk patients. The
      lesions were subjected to LIFE (laser-induced fluorescence endoscopy)
      bronchoscopy and molecular follow-up over a 4 year period. The presence and the
      persistence of specific genetic alterations were correlated with recurrence or
      progression of the disease on follow-up. Molecular lesions considered as highly
      predictive of invasion could be prospectively used as diagnostic markers of high
      risk for lung cancer in exposed patients.

PMID- 12234695
TI  - Staging small cell lung cancer: Veterans Administration Lung Study Group versus
      International Association for the Study of Lung Cancer--what limits limited
      disease?
AB  - Small cell lung cancer (SCLC) is usually classified into a two-stage system,
      limited (LD) and extensive disease (ED). However, the criteria for these two
      categories remain controversial. The widely used Veterans Administration Lung
      Study Group (VALG) definition of LD includes patients with primary tumor and
      nodal involvement limited to one hemithorax. In contrast, the International
      Association for the Study of Lung Cancer (IASLC) recommends that LD should
      additionally include all patients without distant metastasis. As a consequence,
      since treatment modalities for LD and ED could be different, individual clinical
      outcome of SCLC patients may be influenced by the staging system chosen. Among
      109 consecutive SCLC patients treated in our clinic between 1989 and 1999 (mean
      age 68+/-9.1 years, 81% male) 23 patients (21%) could be either classified as LD
      or ED (LD-ED), depending on the staging system used. The prognosis of this
      overlapping group (LD-ED: median survival 291 days) was not statistically
      different from patients with limited disease defined by VALG criteria (LD-VALG:
      385 days, log-rank test P = 0.42). On the other hand the survival difference
      between LD-ED patients and the ED-IASLC population was relevant (ED-IASLC: 208
      days, P = 0.05), indicating that LD-ED patients should rather be included in the
      LD category. This is further supported by the results of a multivariate Cox
      regression analysis with all clinically relevant data. Only stage as defined by
      IASLC criteria was an independent prognostic factor in the likelihood-ratio
      forward (hazard ratio = 1.94, CI = 1.26-2.99; P = 0.005) and backward model
      (hazard ratio = 1.76, CI: 1.12-2.76; P = 0.012), confirming the higher
      discriminatory power of the IASLC definition. In conclusion, the IASLC staging
      criteria for SCLC patients have a higher prognostic impact and are therefore
      preferable in clinical practice and future therapeutic trials.

PMID- 12234696
TI  - Preoperative cytodiagnosis of very small-sized peripheral-type primary lung
      cancer.
AB  - To demonstrate the importance of preoperative diagnosis of pulmonary cancers
      presenting as peripheral small-sized solitary shadows we evaluated the results of
      morphologic definitive diagnosis together with various clinical factors in 91
      tumors with less than 15-mm diameter resected surgically between 1983 and 1999.
      Histologically, these tumors consisted of 73 adenocarcinomas, nine squamous cell
      carcinomas, and nine other types. Regarding the pathologic stage, 57 tumors were
      classified in stage IA, three in IB, six in IIA, seven in IIIA, 14 in IIIB, and
      four in IV. Comparing various biopsy techniques, the sensitivity of preoperative
      cytodiagnosis was 43.7% for transbronchial brushing (n = 48), 52.9% for
      transbronchial forceps biopsy-stamp cytology (n = 51), 66.6% for transbronchial
      fine needle aspiration (n = 78), and 85.0% for percutaneous fine needle
      aspiration (n = 20). The overall sensitivity of preoperative cytodiagnosis was
      79.0% for transbronchial biopsy (n = 81), and 87.3% for transbronchial and
      percutaneous biopsy (n = 87). Of 73 clinical N0 cases in which lobectomy was
      performed, 10 cases (13.6%) were diagnosed as between pathological degrees N1, N2
      and N3. However, lung cancer cases with less than 10-mm diameter did not have
      lymph node metastasis. Our study of histologic differentiation showed that all
      cases of well-differentiated adenocarcinomas (n = 20) were pathological degree
      N0. The overall sensitivity of preoperative diagnosis increased to 89.1% in cases
      (n = 74) of tumors with 11-15-mm diameter. The sensitivity of cytodiagnosis for
      peripheral small-sized primary lung cancers is high, and we can estimate
      histological differentiation based on the cytological findings. Therefore,
      cytodiagnosis is an effective and indispensable diagnostic method for
      determination of the optimal treatment approach, including approaches such as
      intentionally limited resection.

PMID- 12234697
TI  - Remediastinoscopy after neoadjuvant therapy for non-small cell lung cancer.
AB  - Despite technical difficulties due to mediastinal fibrosis, remediastinoscopy can
      be a valuable tool in the restaging of non-small cell lung cancer after
      neoadjuvant therapy. The aim of our study was to evaluate the feasibility,
      sensitivity and accuracy of remediastinoscopy. From November 1994 to July 2001 we
      performed a remediastinoscopy in 27 patients after neoadjuvant therapy. Their age
      ranged from 35 to 80 years (mean 61.9+/-11.9). In all 27 patients it was possible
      to perform a remediastinoscopy without major technical difficulties and take
      biopsies of the lymph nodes that were initially invaded by tumour.
      Remediastinoscopy was positive in 11 patients (40.7%) and negative in 16 (59.3%).
      In the 11 patients with a positive remediastinoscopy a complete resection was not
      judged possible and therefore, an unnecessary thoracotomy was avoided. In four
      patients, remediastinoscopy turned out to be false negative. So, in our series,
      sensitivity was 73%, specificity 100% and accuracy 85%. The positive and negative
      predictive values were 100 and 75%, respectively. Previous mediastinoscopy is no
      contra-indication for a repeat one after neoadjuvant therapy. Although
      sensitivity and accuracy are lower than that of a first mediastinoscopy,
      remediastinoscopy is useful to select patients for surgical resection after
      induction therapy.

PMID- 12234698
TI  - Large cell neuroendocrine carcinoma of the lung: pathological study and clinical
      outcome of 18 resected cases.
AB  - Large cell neuroendocrine carcinoma of the lung (LCNEC) has been recently
      redefined by the World Health Organisation (WHO) classification but the
      appropriate treatment remains unclear. We reviewed 18 consecutive resected cases
      of LCNEC. Two pathologists assessed diagnosis by applying rigorously the last WHO
      criteria. We reported the pathological features and the clinical outcome of this
      particular tumour. All patients were men with a median age of 63 years.
      Clinicopathologic stages corresponded to stage I (n = 8), II (n = 8) and IIIA (n
      = 2). All patients were treated as non-small cell lung carcinoma (NSCLC) and
      underwent surgery without any adjuvant treatment except four post-operative
      radiotherapy for N2 or T3 disease. The evolution was pejorative for 14 patients:
      one patient died of post-operative complications and 13 patients relapsed with
      distant metastases that occurred in 10 cases within 6 months after surgery. One
      year survival rate was 27% and survival rate at the end of follow-up was 22%,
      which were both less than expected for stage-comparable NSCLC. Survival was
      neither influenced by lymph node status nor by pathological or molecular
      findings. Among the 10 evaluable patients with metastatic disease that received
      palliative platin-etoposide chemotherapy only two had partial tumour regressions
      (20%). Our study suggests that applying to LCNEC the NSCLC standard treatment
      lead to poor prognosis even in localised disease with a high incidence of early
      metastatic spread and a low response rate to chemotherapy. This way of relapse
      underlies the necessity of an efficient chemotherapy in order to improve
      survival.

PMID- 12234699
TI  - Hematogenous dissemination of lung cancer cells during surgery: quantitative
      detection by flow cytometry and prognostic significance.
AB  - Shedding of neoplastic cells into the circulation is an essential event for the
      hematogenous metastasis of solid tumors. Recently, several studies reported that
      a high frequency of cancer cells could be detected in the bloodstream during
      surgery. The intraoperative detection of hematogenous dissemination of cancer
      cells was able to identify a subset of patients with malignant diseases at high
      risk for postoperative metastasis and to predict a poor prognosis. In order to
      evaluate the association between intraoperative dissemination of cancer cells and
      postsurgical survival of patients with non-small cell lung cancer (NSCLC), we
      developed a flow cytometric assay for specific detection of lung cancer cells in
      the blood. The monocyte-enriched population in the blood was separated by a
      modified Ficoll-Hypaque density centrifugation and then labeled with a
      combination of monoclonal antibodies specific for CD45, cytokeratin (CK) and two
      antigens expressed on lung cancer cells (2F7 and S5A). The assay could detect
      quantitatively lung cancer cells (defined as CD45(-1) CK(+) 2F7/S5A(+) cells),
      with the sensitivity limit of one cancer cell in 10(5) normal leukocytes. The
      specificity for lung cancer was 97%, which was calculated from the results of
      healthy subjects (20 cases) and patients affected with benign pulmonary diseases
      (26 cases) or esophageal cancer (14 cases). Blood samples of 31 NSCLC patients
      were collected from pulmonary vein during open thoracic surgery. Fifteen of them
      (48.4%) were found to have positive test results. The average cancer cell counts
      in these cases were 0.306 x 10(6)/l. Patients under 55 years of age had a
      significantly higher percentage of positive findings than those over 55 years of
      age (P < 0.05). The positive rate increased over the stages and lymph node
      status, but the differences were not statistically significant. Moreover,
      patients with squamous cell carcinoma at later stages (stages III and IV) had an
      increased frequency of positive test results than those at earlier stages (stages
      I and II, P < 0.05). In contrast, no such a difference was found in cases with
      adenocarcinoma. On the basis of 30-months follow-up date, the median survival
      time and 2-year survival rate for patients with positive and negative findings
      were 11 vs. 27 months, and 26.7 vs. 62.5%, respectively. There was a
      statistically significant difference between overall survival curves that favored
      the patients with negative test results (P = 0.023). Multivariate analysis
      indicated the stage of disease and the positive test results as two independent
      factors that affected survival time (P = 0.017 and 0.027). When a comparison was
      made within the patients at stages III and IV, the presence of cancer cells in
      blood was associated with a significantly shorter survival. These data indicate
      that the hematogenous dissemination of lung cancer cells during surgery would be
      one of the mechanisms of postoperative tumor metastasis. The detection of these
      cells may help to identify patients with poor prognosis.

PMID- 12234700
TI  - The influence of gender on survival and tumor recurrence following adjuvant
      therapy of completely resected stages II and IIIa non-small cell lung cancer.
AB  - This study evaluates the influence of gender on survival and tumor recurrence
      following adjuvant therapy of completely resected stages II and IIIa non-small
      cell lung cancer (NSCLC). The Eastern Cooperative Oncology Group conducted a
      randomized prospective trial of adjuvant therapy in patients with completely
      resected stages II and IIIa NSCLC. A laboratory correlative study assessed the
      prevalence and prognostic significance of p53 and K-ras mutations. Patients were
      randomized to receive either radiotherapy (RT) alone or four cycles of cisplatin
      and VP-16 administered concurrently with radiotherapy (CRT). Median survival was
      35 months for the 285 men and 41 months for the 203 women enrolled in the study
      (P = 0.12). The relative risk (RR) of death for men vs women was 1.19 (95%
      confidence interval [CI], 0.95-1.49). Median survival of the 147 men and 95 women
      randomized to the RT arm was 39 months each (P = 0.35). Median survival of the
      138 men and 108 women randomized to the CRT arm was 30 and 42 months,
      respectively (P = 0.18). Disease recurrence patterns were similar between the
      genders. Univariate and multivariate analyses demonstrated improved survival for
      women with tumors of non-squamous histology (P < 0.01). The distribution of p53
      and K-ras mutations was similar between the genders and had no influence on
      survival. Gender does not influence survival following adjuvant RT or CRT
      administered to patients with completely resected stages II and IIIa NSCLC.
      However, women with non-squamous histology have increased survival when compared
      to men.

PMID- 12234701
TI  - Study of either ifosfamide or teniposide compared to a standard chemotherapy for
      extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group
      randomized study (E1588).
AB  - This randomized study of previously untreated patients with extensive disease
      small cell lung cancer was designed (a) to compare the survival of patients
      treated with either effective standard chemotherapy or an investigational anti
      cancer drug as initial therapy and (b) to evaluate response rates and toxic
      effects of such therapies. One hundred and thirty-five patients were randomly
      assigned to receive as initial therapy, either the standard CAV regimen-
      cyclophosphamide (1000 mg/m(2)), doxorubicin (50 mg/m(2)) and vincristine (1.4
      mg/m(2)) every 3 weeks--or the phase II drugs ifosfamide (1.5 gm/m(2)/days 1-5)
      with mesna (300 mg/m(2)) dose at 0, 4 and 8 h after IV daily ifosfamide every 3
      weeks or teniposide (60 mg/m(2)/days 1-5) every 3 weeks. Nonresponders received
      salvage chemotherapy-etoposide (120 mg/m(2) on days 1, 2 and 3) and cisplatin (60
      mg/m(2) on day 1), repeated every 3 weeks. Among the 46 patients on CAV, there
      were two complete and 24 partial responses (56%). Among the 43 patients on
      ifosfamide, there were three complete and 18 partial responses (49%), while among
      the 46 patients on teniposide, there were two complete and 18 partial responses
      (43%). Eighty-three of the patients proceeded onto salvage regimen, of which 81
      were analyzable for response and toxicity. Among the 81 patients who continued on
      salvage therapy and were evaluable for response, the overall best response rate
      was 61% for CAV+salvage, 54% for ifosfamide+salvage, and 53% for
      teniposide+salvage. These rates were not significantly different (P=0.962). Of
      the 135 analyzable patients, 130 (96%) have died. The estimated median survival
      time was 42 weeks for CAV patients, 43 weeks for ifosfamide, and 38 weeks for
      teniposide. Seven patients survived longer than 2 years (four on CAV, one on
      ifosfamide and two on teniposide). There were 29 life-threatening complications
      to the induction regimen (22 (48%) on CAV, four (9%) on ifosfamide and three (7%)
      on teniposide) and seven lethal complications (two on CAV, four on ifosfamide and
      one on teniposide). The treatments were significantly different with respect to
      the overall degree of toxicity (P < 0.0001) with CAV being more toxic. The data
      of this study, like the previous ECOG study suggests that the administration of a
      new agent followed by effective salvage chemotherapy in the treatment of
      extensive disease small cell lung cancer may have no adverse effect on survival.

PMID- 12234702
TI  - Phase II study of weekly irinotecan and carboplatin for refractory or relapsed
      small-cell lung cancer.
AB  - We designed a phase II study of weekly irinotecan (CPT-11) and carboplatin for
      refractory or relapsed small cell lung cancer (SCLC) and assessed the response
      rate, survival, and toxicity. Twenty-nine patients with refractory or relapsed
      SCLC were entered onto the trial. The median time off chemotherapy was 3.5 months
      (range: 0.8-12.9). Patients were treated at 4-week intervals using CPT-11 (50
      mg/m(2) intravenously on days 1, 8 and 15) plus carboplatin (AUC = 2 mg/ml min,
      intravenously on days 1, 8, 15). All patients were assessable for toxicity and
      survival; 28 patients were assessable for response. There were nine partial
      responses (PRs). Overall response rate was 31.0% (95% CI: 15.3-50.8%). The median
      time to progression was 3.5 months. Median survival time was 6.1 months. Major
      toxicity was myelosuppression. Grade 3 to 4 neutropenia and thrombocytopenia
      occurred in 52 and 21% of patients, respectively. Grade 3-4 diarrhea was observed
      in 7%. There was one treatment-related death due to febrile neutropenia and
      sepsis. This combination of CPT-11 and carboplatin seems to be active second-line
      regimen with acceptable toxicity against small cell lung cancer.

PMID- 12234703
TI  - IV international conference on prevention and early detection of lung cancer,
      Reykjavik, Iceland, August 9-12, 2001.

PMID- 12234704
TI  - Cutaneous dendritic cells in the crossfire between innate and adaptive immunity.

PMID- 12234705
TI  - Effects of topical vehicles on growth of the lipophilic Malassezia species.
AB  - In the present study, the abilities of major Malassezia species, M. sympodialis,
      M. globosa and M. furfur, to assimilate topical agents, which have been widely
      used as a material of ointment for skin diseases, were tested. Obvious growth of
      M. furfur on GYEP agar plate was noted in the presence of white petrolatum,
      purified white petrolatum, hydrophilic ointment and heparinoid in hydrophilic
      ointment, and also M. sympodialis showed similar growth when they were cultured
      with hydrophilic or heparinoid in hydrophilic ointment. In contrast, M. globosa
      did not grow on GYEP in the presence of the any topical agents tested. These
      results suggest that Malassezia species, especially M. furfur and M. sympodialis,
      assimilate several topical agents and showed the drug-depended cell growth.

PMID- 12234706
TI  - Dysfunction of dermal fibroblasts induced by advanced glycation end-products
      (AGEs) and the contribution of a nonspecific interaction with cell membrane and
      AGEs.
AB  - Advanced glycation end-products (AGEs) have been reported to accumulate in the
      dermal skin. However, it remains unknown whether the AGEs interact with the
      dermal fibroblasts and influence their function. Previously, we demonstrated that
      AGEs hastened photoaging of the skin by means of active oxygen species such as
      *O(2)(-), H(2)O(2), and *OH, generated during UVA irradiation. The purpose of the
      present study was to clarify the influence of AGEs on the functions of dermal
      fibroblasts under physiological conditions. It was found that AGEs decreased both
      hyaluronic acid (HA) synthesis and activity of elastase-type matrix
      metalloproteinase (ET-MMP). Because the reactions of both HA synthesis and ET-MMP
      were found to take place at the cell membrane region, it appeared that AGEs
      modulated cellular dysfunction through an interaction with the cell membrane. To
      clarify the mechanisms of these dysfunction in relation to AGEs, we examined the
      interaction between AGEs and cell membranes, and obtained the following results:
      (1) AGEs associated with the cell membranes and liposomal membrane prepared with
      phosphatidyl choline; (2) AGEs hydrophobically modified the circumstances of the
      cell membrane and liposome membrane as evaluated by experiments using a
      fluorescence probe; (3) AGEs increased the fluidity of the cell membrane and
      liposomal membrane as estimated by ESR spin-labeling using 5-doxylstearic acid;
      and (4) AGEs accelerated lactate dehydrogenase (LDH) leakage from the cells. On
      the basis of these experimental results, we proposed that AGEs modulated cell
      function through a nonspecific interaction with the membranes of dermal
      fibroblasts.

PMID- 12234707
TI  - Lack of association of TNF-238A and -308A in Japanese patients with psoriasis
      vulgaris, psoriatic arthritis and generalized pustular psoriasis.
AB  - Tumor necrosis factor (TNF)-alpha is one of the proinflammatory cytokines and
      immunomodulators, and has an important pathogenetic role in psoriasis. The TNF
      alpha gene (TNFA) is in the human leukocyte antigen (HLA) class III locus on
      chromosome 6, which might be related to the pathogenesis of psoriasis. It has
      been suggested that some polymorphisms of the TNFA gene promoter, especially G to
      A conversions at nt-238 and -308 (TNF-238A and -308A), may be associated with
      psoriasis in Caucasians. We investigated single nucleotide polymorphisms (SNPs)
      of the TNFA gene promoter in Japanese psoriasis patients, including 18 with
      psoriasis vulgaris (PsV), 11 with psoriatic arthritis (PsA), two with generalized
      pustular psoriasis (GPP), and six with GPP with arthritis. The DNA fragment of
      the TNFA gene from nt-400 to -69 was amplified by polymerase chain reaction (PCR)
      and the products were sequenced. Although TNF-238A and other polymorphisms were
      not found in PsV and psoriatic arthritis patients, one male patient with GPP and
      PsA had TNF-308A. This suggests that TNFA gene promoter polymorphism in the
      region examined is less associated with the pathogenesis of psoriasis in Japanese
      patients, however there might be the possibility that TNFA gene promoter
      polymorphism is associated with GPP. Further investigation will be required to
      prove this.

PMID- 12234708
TI  - Size control of decorin dermatan sulfate during remodeling of collagen fibrils in
      healing skin.
AB  - Recently it has been reported that the molecular size of decorin dermatan sulfate
      (DS) was increased in healing skin after hapten application and that the
      elongated DS was distributed in enlarged interfibrillar space among thin collagen
      fibrils in situ. Here we show that such modulation of the length of decorin DS is
      temporary. Although the size of decorin DS was evidently increased on day 15, it
      decreased to almost normal size on day 35 when the altered disaccharide
      composition of DS was also recovered. Electron microscopic observation revealed
      that elongated decorin DS was localized among thin collagen fibrils packed
      loosely in hapten-treated skin on day 15. In contrast, decorin DS of normal size
      was distributed among thick collagen fibrils packed tightly on day 35. These
      results suggest that size control of decorin DS plays important roles in
      organization of collagen fibrils into bundles by regulating interfibrillar space
      in healing skin, particularly in maturation of collagen fibrils through
      shortening of decorin DS in later stages of healing.

PMID- 12234709
TI  - Keratin 1 and keratin 10 mutations causing epidermolytic hyperkeratosis in
      Chinese patients.
AB  - Epidermolytic hyperkeratosis (EHK) is a rare dominantly inherited skin disorder
      with erythroderma and hyperkeratosis. Mutations have been found in keratin 1 (K1)
      or keratin 10 (K10) gene. In the present study, we reported three sporadic and
      one familial Chinese EHK patients with their mutation findings. All the mutations
      turned out to be single heterozygous point substitutions. A novel mutation
      designated as E477K of K1 was identified in one patient, and previous reported
      mutations in codon 156 of K10, i.e. R156S, R156P, R156H were found in other
      patients. This is the first report of the keratin mutations in Chinese kindreds.
      The results showed that the possible correlation between the genotype and
      phenotype in these patients was complex, not only depended on the position of the
      mutation but also on the actual amino acid substitution. And palmoplantar
      keratoderma (PPKD) can be an accompanied symptom caused by either K1 or K10
      mutation.

PMID- 12234710
TI  - Expression of inducible nitric oxide synthase in skin lesions of acute herpes
      zoster.
AB  - Histopathologically, the skin lesions of acute herpes zoster (AHZ) are
      characterized by epidermal necrotic vesicles with inflammation. Nitric oxide (NO)
      is generated from L-arginine by nitric oxide synthase (NOS), and immune
      inflammation involves the activation of NOS in both effector cells and target
      cells. NO can cause apoptosis and necrosis of target cells such as keratinocytes.
      We proposed that a large burst of NO in AHZ may cause the epidermal necrosis.
      Skin biopsies were taken from 13 patients with AHZ. The expression of inducible
      type NOS (iNOS) was examined by immunoperoxidase staining and reverse
      transcription-polymerase chain reaction (RT-PCR). In the skin specimen of AHZ,
      moderate-to-strong staining for iNOS was observed in inflammatory cells and
      necrotic keratinocytes, while weak staining was observed in non-necrotic
      peripheral keratinocytes. RT-PCR using skin specimen of AHZ corroborated the
      immunoperoxidase findings, yielding bright bands for iNOS. Normal control skin
      showed minimal or negative expression both by immunoperoxidase stains and RT-PCR.
      Increased expression of iNOS is consistent with the hypothesis that high level of
      NO induced by iNOS may be associated with the epidermal necrosis with
      inflammation seen in the skin lesions of AHZ.

PMID- 12234711
TI  - Repeated cationic multilamellar liposome-mediated gene transfer enhanced
      transduction efficiency against murine melanoma cell lines.
AB  - We investigated whether repeated cationic multilamellar liposome-mediated gene
      transfers enhanced the transduction efficiency against murine melanoma cell lines
      and experimental subcutaneous melanoma. In the former, the murine melanoma cell
      line, B16F10, was transfected by our original cationic multilamellar liposomes
      containing pVLacZ, which express beta-galactosidase in eukaryotic cells. Cells
      were exposed to the liposomes in a single, double, or triple procedure during the
      cell logarithmic proliferative period. We then evaluated the transduction
      efficiency by X-gal staining and beta-galactosidase assay. The number of positive
      cells and level of beta-galactosidase activity were significantly increased by
      repeated exposures compared with a single one. Cells transfected by the
      fluorescently labeled cationic liposome containing pEGFP-C1 showed both an
      increased uptake of liposomes and an increased number of EGFP expression cells
      following repeated exposures. In the latter, murine subcutaneous melanomas, which
      were made by transplantation of B16F10 in C57BL6 mice, were transfected by same
      liposomes. Subcutaneous melanomas were exposed to the liposomes in a single,
      double, or triple procedure. We then evaluated the transduction efficiency by the
      beta-galactosidase assay. The level of beta-galactosidase activity was
      significantly increased by repeated exposures compared with a single one. The
      results indicate that repeated exposures to the liposomes enhanced the
      transduction efficiency toward murine melanoma cells and experimental
      subcutaneous melanoma, and may provide a basis for the repeated-exposure protocol
      for human trials.

PMID- 12234712
TI  - Domain structure of erythrocyte membranes in psoriasis: an EPR study.
AB  - Membrane fluidity of erythrocytes from psoriatic patients in active and inactive
      period of the disease was studied by electron paramagnetic resonance (EPR).
      Comparison of simulated and experimental EPR spectra of erythrocyte membranes
      from controls and psoriatics showed that they are essentially superimposition of
      three components; two regions with a high degree of order of the lipid acyl
      chains and one region with poor alignments of hydrocarbon chains (with a small
      order parameter). In psoriatic erythrocytes not only the portion of the most
      rigid domain was enlarged, but also the order parameter of this domain was
      increased, while the order parameters of two other domains were the same than in
      normal erythrocytes. Results obtained in this article showed that the portion of
      the most rigid domain (W(A)) better correlated with polymorphonuclear elastase
      (PMN elastase) than with PASI score. Additionally, correlation between PMN
      elastase and W(A) in the active period of the disease was observed to be higher
      than in the inactive period. Therefore, portion of the most ordered domain (W(A))
      seems to be a good marker for evaluation of the disease activity in psoriatic
      patients.

PMID- 12234713
TI  - Eotaxin gene single nucleotide polymorphisms in the promoter and exon regions are
      not associated with susceptibility to atopic dermatitis, but two of them in the
      promoter region are associated with serum IgE levels in patients with atopic
      dermatitis.
AB  - Eotaxin is believed to play an important role in atopic dermatitis (AD) as a
      potent chemoattractant and activator of eosinophils and Th2 lymphocytes. The
      eotaxin gene is located at chromosome 17q21.1-q21.2, and linkage findings of AD
      on chromosome 17 were reported. Recently we have identified single nucleotide
      polymorphisms (SNPs) of eotaxin gene (-426C > T, -384A > G, 67G > A). To learn
      whether eotaxin gene SNPs are associated with susceptibility to AD or phenotypes
      of AD, we investigated the genotype frequencies at each SNP of the gene in AD
      patients and in controls. We examined 140 Japanese AD patients and 140 healthy
      Japanese individuals. Genotyping was performed using the polymerase chain
      reaction-restriction fragment length polymorphism method. No significant
      difference was observed in allele or genotype frequencies of any SNP between AD
      patients and controls. Serum immunoglobulin E (IgE) levels were significantly
      lower in CT and TT genotype than in CC (P = 0.038) in -426C > T SNP, and lower in
      GG than in AA and AG with borderline significance (P = 0.053) in -384A > G SNP in
      AD patients. Eotaxin gene SNPs in the promoter and exon regions are not
      associated with susceptibility to AD, but two of them in the promoter region are
      associated with phenotype of AD.

PMID- 12234714
TI  - Uniqueness of medical data mining.
AB  - This article addresses the special features of data mining with medical data.
      Researchers in other fields may not be aware of the particular constraints and
      difficulties of the privacy-sensitive, heterogeneous, but voluminous data of
      medicine. Ethical and legal aspects of medical data mining are discussed,
      including data ownership, fear of lawsuits, expected benefits, and special
      administrative issues. The mathematical understanding of estimation and
      hypothesis formation in medical data may be fundamentally different than those
      from other data collection activities. Medicine is primarily directed at patient
      care activity, and only secondarily as a research resource; almost the only
      justification for collecting medical data is to benefit the individual patient.
      Finally, medical data have a special status based upon their applicability to all
      people; their urgency (including life-or-death); and a moral obligation to be
      used for beneficial purposes.

PMID- 12234715
TI  - Confidentiality issues for medical data miners.
AB  - The first task in any medical data mining effort is ensuring patient
      confidentiality. In the past, most data mining efforts ensured confidentiality by
      the dubious policy of withholding their raw data from colleagues and the public.
      A cursory review of medical informatics literature in the past decade reveals
      that much of what we have "learned" consists of assertions derived from
      confidential datasets unavailable for anyone's review. Without access to the
      original data, it is impossible to validate or improve upon a researcher's
      conclusions. Without access to research data, we are asked to accept findings as
      an act of faith, rather than as a scientific conclusion. This special issue of
      Artificial Intelligence in Medicine is devoted to medical data mining. The
      medical data miner has an obligation to conduct valid research in a way that
      protects human subjects. Today, data miners have the technical tools to merge
      large data collections and to distribute queries over disparate databases. In
      order to include patient-related data in shared databases, data miners will need
      methods to anonymize and deidentify data. This article reviews the human subject
      risks associated with medical data mining. This article also describes some of
      the innovative computational remedies that will permit researchers to conduct
      research AND share their data without risk to patient or institution.

PMID- 12234716
TI  - Data mining a diabetic data warehouse.
AB  - Diabetes is a major health problem in the United States. There is a long history
      of diabetic registries and databases with systematically collected patient
      information. We examine one such diabetic data warehouse, showing a method of
      applying data mining techniques, and some of the data issues, analysis problems,
      and results. The diabetic data warehouse is from a large integrated health care
      system in the New Orleans area with 30,383 diabetic patients. Methods for
      translating a complex relational database with time series and sequencing
      information to a flat file suitable for data mining are challenging. We discuss
      two variables in detail, a comorbidity index and the HgbA1c, a measure of
      glycemic control related to outcomes. We used the classification tree approach in
      Classification and Regression Trees (CART) with a binary target variable of
      HgbA1c >9.5 and 10 predictors: age, sex, emergency department visits, office
      visits, comorbidity index, dyslipidemia, hypertension, cardiovascular disease,
      retinopathy, end-stage renal disease. Unexpectedly, the most important variable
      associated with bad glycemic control is younger age, not the comorbiditity index
      or whether patients have related diseases. If we want to target diabetics with
      bad HgbA1c values, the odds of finding them is 3.2 times as high in those <65
      years of age than those older. Data mining can discover novel associations that
      are useful to clinicians and administrators [corrected].

PMID- 12234717
TI  - Using dependency/association rules to find indications for computed tomography in
      a head trauma dataset.
AB  - Analysis of a clinical head trauma dataset was aided by the use of a new, binary
      based data mining technique, termed Boolean analyzer (BA), which finds
      dependency/association rules. With initial guidance from a domain user or domain
      expert, the BA algorithm is given one or more metrics to partition the entire
      dataset. The weighted rules are in the form of Boolean expressions. To augment
      the analysis of the rules produced, we applied a probabilistic interestingness
      measure (PIM) to order the generated rules based on event dependency, where
      events are combinations of primed and unprimed variables. Interpretation of the
      dependency rules generated on the clinical head trauma data resulted in a set of
      criteria that identified minor head trauma patients needing computed tomography
      (CT) scans. The BA criteria contained fewer variables than were found using
      recursive partitioning of Chi-square values (five variables versus seven
      variables, respectively). The BA five-variable criteria set was more sensitive
      but less specific than the seven-variable Chi-square criteria set. We believe
      that the BA method has broad applicability in the medical domain, and hope that
      this paper will stimulate other creative applications of the technique.

PMID- 12234718
TI  - Analysis of respiratory pressure-volume curves in intensive care medicine using
      inductive machine learning.
AB  - We present a case study of machine learning and data mining in intensive care
      medicine. In the study, we compared different methods of measuring pressure
      volume curves in artificially ventilated patients suffering from the adult
      respiratory distress syndrome (ARDS). Our aim was to show that inductive machine
      learning can be used to gain insights into differences and similarities among
      these methods. We defined two tasks: the first one was to recognize the
      measurement method producing a given pressure-volume curve. This was defined as
      the task of classifying pressure-volume curves (the classes being the measurement
      methods). The second was to model the curves themselves, that is, to predict the
      volume given the pressure, the measurement method and the patient data. Clearly,
      this can be defined as a regression task. For these two tasks, we applied C5.0
      and CUBIST, two inductive machine learning tools, respectively. Apart from
      medical findings regarding the characteristics of the measurement methods, we
      found some evidence showing the value of an abstract representation for
      classifying curves: normalization and high-level descriptors from curve fitting
      played a crucial role in obtaining reasonably accurate models. Another useful
      feature of algorithms for inductive machine learning is the possibility of
      incorporating background knowledge. In our study, the incorporation of patient
      data helped to improve regression results dramatically, which might open the door
      for the individual respiratory treatment of patients in the future.

PMID- 12234719
TI  - Logistic-based patient grouping for multi-disciplinary treatment.
AB  - Present-day healthcare witnesses a growing demand for coordination of patient
      care. Coordination is needed especially in those cases in which hospitals have
      structured healthcare into specialty-oriented units, while a substantial portion
      of patient care is not limited to single units. From a logistic point of view,
      this multi-disciplinary patient care creates a tension between controlling the
      hospital's units, and the need for a control of the patient flow between units. A
      possible solution is the creation of new units in which different specialties
      work together for specific groups of patients. A first step in this solution is
      to identify the salient patient groups in need of multi-disciplinary care.
      Grouping techniques seem to offer a solution. However, most grouping approaches
      in medicine are driven by a search for pathophysiological homogeneity. In this
      paper, we present an alternative logistic-driven grouping approach. The starting
      point of our approach is a database with medical cases for 3,603 patients with
      peripheral arterial vascular (PAV) diseases. For these medical cases, six basic
      logistic variables (such as the number of visits to different specialist) are
      selected. Using these logistic variables, clustering techniques are used to group
      the medical cases in logistically homogeneous groups. In our approach, the
      quality of the resulting grouping is not measured by statistical significance,
      but by (i) the usefulness of the grouping for the creation of new multi
      disciplinary units; (ii) how well patients can be selected for treatment in the
      new units. Given a priori knowledge of a patient (e.g. age, diagnosis), machine
      learning techniques are employed to induce rules that can be used for the
      selection of the patients eligible for treatment in the new units. In the paper,
      we describe the results of the above-proposed methodology for patients with PAV
      diseases. Two groupings and the accompanied classification rule sets are
      presented. One grouping is based on all the logistic variables, and another
      grouping is based on two latent factors found by applying factor analysis. On the
      basis of the experimental results, we can conclude that it is possible to search
      for medical logistic homogenous groups (i) that can be characterized by rules
      based on the aggregated logistic variables; (ii) for which we can formulate rules
      to predict to which cluster new patients belong.

PMID- 12234721
TI  - Syntactic reasoning and pattern recognition for analysis of coronary artery
      images.
AB  - This paper presents a new approach to the application of structural pattern
      recognition methods for image understanding, based on content analysis and
      knowledge discovery performed on medical images. This presents in particular
      computer analysis and recognition of local stenoses of the coronary arteries
      lumen. These stenoses are the result of the appearance of arteriosclerosis
      plaques, which in consequence lead to different forms of ischemic cardiovascular
      diseases. Such diseases may be seen in the form of stable or unstable
      disturbances of heart rhythm or infarctions. Analysis of the correct morphology
      of these arteries lumen is possible with the application of the syntactic
      analysis and pattern recognition methods, in particular with the attributed
      grammar of LALR type. In the paper, we shall describe all stages of analysis and
      understanding of images in the context of obtained features, and we shall also
      present the proper algorithm of syntactic reasoning based on the acquired
      knowledge.

PMID- 12234720
TI  - Bayesian learning for cardiac SPECT image interpretation.
AB  - In this paper, we describe a system for automating the diagnosis of myocardial
      perfusion from single-photon emission computerized tomography (SPECT) images of
      male and female hearts. Initially we had several thousand of SPECT images, other
      clinical data and physician-interpreter's descriptions of the images. The images
      were divided into segments based on the Yale system. Each segment was described
      by the physician as showing one of the following conditions: normal perfusion,
      reversible perfusion defect, partially reversible perfusion defect, fixed
      perfusion defect, defect showing reverse redistribution, equivocal defect or
      artifact. The physician's diagnosis of overall left ventricular (LV) perfusion,
      based on the above descriptions, categorizes a study as showing one or more of
      eight possible conditions: normal, ischemia, infarct and ischemia, infarct,
      reverse redistribution, equivocal, artifact or LV dysfunction. Because of the
      complexity of the task, we decided to use the knowledge discovery approach,
      consisting of these steps: problem understanding, data understanding, data
      preparation, data mining, evaluating the discovered knowledge and its
      implementation. After going through the data preparation step, in which we
      constructed normal gender-specific models of the LV and image registration, we
      ended up with 728 patients for whom we had both SPECT images and corresponding
      diagnoses. Another major contribution of the paper is the data mining step, in
      which we used several new Bayesian learning classification methods. The approach
      we have taken, namely the six-step knowledge discovery process has proven to be
      very successful in this complex data mining task and as such the process can be
      extended to other medical data mining projects.

PMID- 12234722
TI  - Mining knowledge for HEp-2 cell image classification.
AB  - HEp-2 cells are used for the identification of antinuclear autoantibodies (ANAs).
      They allow for recognition of over 30 different nuclear and cytoplasmic patterns,
      which are given by upwards of 100 different autoantibodies. The identification of
      the patterns has recently been done manually by a human inspecting the slides
      with a microscope. In this paper, we present results on the analysis and
      classification of cells using image analysis and data mining techniques. Starting
      from a knowledge acquisition process with a human operator, we developed an image
      analysis and feature extraction algorithm. The collection of the dataset was done
      based on an expert's image reading and based on the automatic extracted features.
      A dataset containing 132 features for each entry was set up and given to a data
      mining algorithm to find out the relevant features among this large feature set
      and to construct the classification knowledge. The classifier was evaluated by
      cross validation. The results gave the expert new insights into the necessary
      features and the classification knowledge and show the feasibility of an
      automated inspection system.

PMID- 12234724
TI  - MLO, a novel modulator of plant defenses and cell death, binds calmodulin.

PMID- 12234725
TI  - New frontiers in plant development: from genes to phenotype.

PMID- 12234729
TI  - Toll and interleukin-1 receptor (TIR) domain-containing proteins in plants: a
      genomic perspective.
AB  - Toll and interleukin-1 receptor (TIR) domains were originally described from
      comparisons of proteins found in mammals and Drosophila. They are now known to
      occur in several organisms, with the most TIR proteins being found in
      Arabidopsis: our analysis of the sequenced Arabidopsis genome has revealed the
      presence of at least 135 proteins containing TIR domains. Several novel types of
      TIR-domain-containing proteins are found in Arabidopsis that are not found in
      other genomes. Here, we discuss the roles of TIR-domain-containing proteins in
      pathogen resistance and as candidate signaling modules.

PMID- 12234730
TI  - Alternative splicing of transcripts encoding Toll-like plant resistance proteins 
      what's the functional relevance to innate immunity?
AB  - Innate immunity in plants and animals shares many structural and functional
      homologies, which suggests an ancient origin of cellular defense mechanisms in
      both kingdoms. Pathogen sensing in animal innate immunity is mediated by Toll
      like receptors (TLRs). These receptors have TIR (Toll/interleukin-1 receptor)
      domains and leucine-rich repeats, which are modules also present in many plant
      resistance (R) proteins. Molecular analysis of transcripts encoding animal TLRs
      and Toll-like plant R proteins revealed many cases of alternative splicing.
      Recent studies of the tobacco N and the Arabidopsis RPS4 genes, both encoding
      Toll-like plant R proteins, showed that intron-deprived genes have reduced or no
      activity, suggesting that alternative splicing is a crucial component in these
      signaling pathways.

PMID- 12234731
TI  - Light and shade in the photocontrol of Arabidopsis growth.
AB  - Plants have evolved sophisticated sensing mechanisms that operate through
      phytochromes, perceiving changes in the red:far-red ratio, which trigger
      morphological changes to avoid shade. The shade-avoidance response essentially
      redirects resources and growth potential from the leaf and storage organs into
      increased extension growth to optimize light capture by plants. Recent studies
      implicate ATHB-2, a homeodomain-leucine zipper transcription factor, as a
      regulator of shade-avoidance responses and establish a strong link between this
      factor and auxin signaling. The action of ATHB-2 is likely to generate changes in
      auxin distribution that produce distinct but coordinated effects on different
      cell types across the plant. Future studies should highlight how polarity of
      auxin transport is altered in response to light-quality changes.

PMID- 12234732
TI  - Oxidative stress, antioxidants and stress tolerance.
AB  - Traditionally, reactive oxygen intermediates (ROIs) were considered to be toxic
      by-products of aerobic metabolism, which were disposed of using antioxidants.
      However, in recent years, it has become apparent that plants actively produce
      ROIs as signaling molecules to control processes such as programmed cell death,
      abiotic stress responses, pathogen defense and systemic signaling. Recent
      advances including microarray studies and the development of mutants with altered
      ROI-scavenging mechanisms provide new insights into how the steady-state level of
      ROIs are controlled in cells. In addition, key steps of the signal transduction
      pathway that senses ROIs in plants have been identified. These raise several
      intriguing questions about the relationships between ROI signaling, ROI stress
      and the production and scavenging of ROIs in the different cellular compartments.

PMID- 12234733
TI  - Cell polarization, a crucial process in fungal defence.
AB  - Plant cells responding to fungal attack undergo large morphological alterations,
      along with rapid and extensive metabolic reprogramming. Cytological analysis of
      single infected plant cells revealed a large complexity of interdependent, rapid
      and dynamic changes of a multitude of cellular components. Among these changes
      are major rearrangements of the cytoskeleton, translocation of cytoplasm and of
      the cell nucleus to the fungal penetration site, and local apposition of barrier
      material around this site, which results in massive cell-wall reinforcement. If
      this first line of defence is overcome by the pathogen, in many cases, it is
      followed by hypersensitive plant cell death, which stops growth of the
      penetrating fungus and finally leads to its death. The speed and magnitude of the
      initial defence response appear to be crucial to plant disease resistance.

PMID- 12234734
TI  - Comparison of driving forces in sustainable food production and the future of
      plant biotechnology in Switzerland and China.

PMID- 12234735
TI  - Science and politics: Hans Stubbe and the Institute of Plant Genetics and Crop
      Plant Research at Gatersleben.

PMID- 12234741
TI  - Iatrogenic multiple pregnancy.
AB  - Iatrogenic - physician-made - multiple pregnancies (IMPs) significantly
      contribute to the epidemic of twins and high-order multiples in most developed
      and in many developing countries. The primary etiology for IMPs is treatment of
      reduced fecundity, some but not all of which is associated with specific
      lifestyle changes of women in the second half of the 20th century. IMPs
      contribute to increased perinatal morbidity and mortality related to prematurity
      and low birth weights. In addition, the use of assisted conception techniques
      increases the frequency of monozygotic twinning and related pathology. Because
      assisted conceptions are costly interventions, current numbers of IMPs represent
      a balance between the need to maximize success rates and the desire to minimize
      the untoward outcome rates. We believe that eliminating procedures associated
      with unavoidable IMPs and controlling the number of transferred embryos can
      achieve a significant reduction in the adverse perinatal outcomes and costs
      associated with IMPs.

PMID- 12234742
TI  - Normal and abnormal growth of multiples.
AB  - Growth curves of twins and triplets do not support a growth restriction patterns
      seen in singletons. At the same time that individual members of a twin or a
      triplet set may be smaller than singletons of the same gestational age, only a
      minority are indeed SGA by singleton standards. When comparing the entire 'fetal
      mass' of a multiple pregnancy to that of singletons, multiple gestations are in
      fact growth promoted, and their individual smaller size are better described as
      growth adaptation. Data from large twin and triplet series suggest that
      significant birth weight discordance result from the inability of the uterine
      milieu to equally nurture twins. In order to promote maturity - gestational age -
      mild compensation in the form of size discordance begins after mid-gestation.
      When the uterine environment competently nurtures multiples, total birth weight
      increases and discordance decreases. Failed adaptation, however, may result in
      significant growth discordance and restriction.

PMID- 12234743
TI  - The twin-twin transfusion syndrome.
AB  - The aetiology of twin-twin transfusion syndrome (TTTS), which affects 10-15% of
      monochorionic (MC) twin pregnancies, remains poorly understood. Although all MC
      twins have placental vascular anastomoses, unbalanced intertwin transfusion has
      been shown by ex vivo injection and in vivo Doppler studies of chorionic plate
      vasculature to be mediated by > or =1 arterio-venous anastomoses (AVA) in
      association with absent bi-directional arterio-arterial anastomoses (AAA). TTTS
      presents in the mid trimester with the oligo-polyhydramnios sequence, the donor
      may have a small or non-visible bladder and abnormal umbilical artery Doppler,
      while the recipient has a large bladder and may develop cardiac hypertrophy,
      triscupid regurgitation, and eventually hydrops. Recently, discordant renal renin
      angiotensin expression, endothelin and atrial natriuretic peptide have been
      implicated in the pathogenesis. Survival has increased from <20% to <60-70% with
      modern treatments, although survivors remain at increased risk of antenatally
      acquired cerebral white matter injury, and neurodevelopmental sequelae are
      documented in c.10% (range 5-23%). The recent introduction of a staging system
      for TTTS facilitates selection of therapy with less invasive amnioreduction and
      septostomy preferred for early stage disease, and more aggressive modalities such
      as laser ablation and cord occlusion with their attendant risk of procedure
      related fetal loss, reserved for advanced stage disease.

PMID- 12234744
TI  - Neonatal and long-term outcomes of very low birth weight infants from single and
      multiple pregnancies.
AB  - The revolution in artificial reproductive technologies has resulted in a dramatic
      rise in the incidence of multiple pregnancies. Many of these infants are born
      prematurely, often extremely so. Consequently, perinatal morbidity and mortality
      are highly correlated with plurality. The primary mechanism for this increased
      risk is prematurity. Studies of the relationship between plurality and outcome
      are frequently hampered by major differences in case mix between singletons,
      twins and high multiples. For example, high multiples tend to receive earlier
      prenatal care, receive more antenatal steroids, are more often delivered by
      Caesarean section and more often suffer from respiratory distress syndrome.
      However, recent studies that appropriately account for relevant confounding
      variables have suggested that very low birth weight infants from high multiple
      pregnancies are at excess risk for mortality when compared with twins and
      singletons. This article reviews the current available evidence.

PMID- 12234745
TI  - Neuromaturation of multiples.
AB  - Etiology of preterm birth and degree of maturation are the primary determinants
      of a preterm infant's survival and complications. Multiple gestation increases
      the likelihood of preterm birth but its influence on rate of maturation or
      complications of prematurity has been controversial, primarily because of
      confounding variables (e.g. race, aetiology of preterm delivery, degree of
      prematurity and pregnancy complications). Very low birthweight preterm multiples
      have virtually the same rates of neonatal mortality, complications and
      neuromaturation as preterm singletons of the same gestational age. There is no
      advantage of delivering twins or higher order multiples before 30 weeks
      gestation, unless a fetus decompensates in utero. Survival improves for near term
      intermediate-size preterm multiples while intrauterine growth decelerates and
      placental and fetal neuromaturation accelerate. These data and the high fetal
      death rate at term support delivery of multiples as soon as there is fetal lung
      maturity, and consideration of elective delivery of twins at 35-38 weeks
      gestation and triplets at 33-35 weeks gestation.

PMID- 12234746
TI  - Neurological outcome in twins.
AB  - Twins are at greater risk of death and severe morbidity than singletons which is
      in excess of that attributable to their greater prematurity. Monozygous,
      specifically monochorionic, twins are at greater risk than dichorionic twins. The
      major morbidity is neurological impairment usually presenting as cerebral palsy
      or severe learning disability and frequently, but not always, associated with
      fetal death of a co-twin. The likely pathogenesis of the neurological impairment
      is ischaemia attributable to haemodynamic imbalance via placental vascular
      anastomoses. In addition to the neurological impairment, congenital cardiac,
      renal, intestinal and other anomalies are more common but discordant in
      monozygous twins. It has been hypothesized that cerebral palsy and other
      neurological impairment in apparently singleton infants is attributable to early
      loss of a twin, the 'vanishing' twin phenomenon. It is also postulated that other
      congenital anomalies in singletons may be attributable to the same phenomenon.

PMID- 12234747
TI  - Breast-feeding multiples.
AB  - Human breast milk is the best nutrition for human infants. Its advantages over
      the milk of other species, such as cows, include both a reduced risk for
      infections, allergies and chronic diseases, together with the full nutritional
      requirements for growth and development. Breast-feeding is as important for
      multiples as for singletons. Despite the advantages, multiples receive less
      breast-feeding than singletons. Common reasons for not breast-feeding multiples
      include the fear of not fulfilling the infants' needs and the difficulty of
      coping with the demands on the mother's time. In addition, many multiples are
      delivered prematurely and by Caesarean section. Maternal pain and discomfort
      together with anxiety over the infants' condition are not conducive to successful
      breast-feeding. During lactation, the mother needs to add calories to her daily
      diet. It has been recommended to add approximately 500-600 kcal/day for each
      infant. Thus, between eating, nursing and sleeping, life is very busy for the
      mother of multiples. However, there is evidence that, with appropriate nutrition,
      one mother can nourish more than one infant. Also, simultaneous breast-feeding
      can save much time. Combined efforts of parents, close family, friends and the
      medical team can help to make either full or partial breast-feeding of multiples
      possible. However, when breast-feeding is not possible, health care workers need
      to carefully avoid judgmental approaches that may induce feelings of guilt.

PMID- 12234748
TI  - Educating families, before, during and after a multiple birth.
AB  - Couples who are expecting twins and higher order births need specific information
      and support to help them prepare for the care of their babies. Professionals
      caring for such families should be aware of their special needs and ensure close
      liaison in order to provide a coordinated service throughout the pregnancy and
      early childhood.

PMID- 12234749
TI  - Mourning and psychological issues in multiple birth loss.
AB  - Grief after the death of some or all multiples differs from mourning for a
      singleton loss in many important respects. A review of the unique features of
      grief for a multiple birth loss is followed by practical suggestions for empathic
      care. Cherished mementos and photos, and disposition options for deceased
      children are discussed. Counselling needs of parents and siblings are detailed,
      and management options for many complex pregnancy and infant loss scenarios are
      presented. The abundant resources listed will help caregivers and families better
      cope with one of the most difficult complications of plural parenthood.

PMID- 12234750
TI  - Allee effect, spatial structure and species coexistence.
AB  - Both positive and negative interactions among species are common in communities.
      Until recently, attention has focused on negative interactions such as
      competition. However, the importance of positive interactions such as the Allee
      effect has recently been recognized. We construct a single-patch model that
      incorporates both an Allee effect and competition between two species. A species
      that experiences an Allee effect cannot establish in a patch which is already
      occupied by a competitor unless its density is over a critical value. This
      effect, when translated into a metapopulation, makes migrants of a species unable
      to colonize patches where another species has established. This interaction
      between the Allee effect and inter-specific competition creates and stabilizes
      spatial segregation of species. Therefore, under circumstances in which
      competition would preclude local coexistence, the presence of an Allee effect can
      allow coexistence at a metapopulation scale. Furthermore, we found that a species
      can resist displacement if stronger competitors experience an Allee effect.

PMID- 12234751
TI  - Population dynamics of clock-controlled biological species: models and why
      circadian rhythms are circadian.
AB  - Conventional models of population dynamics of biological species do not take into
      account the fact that activity of most living organisms is under control of
      biological clocks, which are oscillators with periods near 1 day, 1 year, and so
      on. Here proposed are new categories of population dynamics models which are
      combinations of Lotka-Volterra type of equations (as a simplest example; in fact,
      an arbitrary type may be used) and equations of the biological oscillators. Such
      models may be particularly useful in addressing to those problems which are
      inaccessible with conventional models. A simple example of such models with
      distributed clock periods is proposed and studied numerically and analytically to
      consider why periods of biological rhythms are not precisely one day or one year,
      etc., as is often questioned. For this purpose, a notion of survival index is
      introduced to measure the degree of success in survival. It turns out that clock
      periods equal or close to that of the milieu are not necessarily advantageous for
      survival and can even lead to extinction; survival is then most successful at the
      edge of entrainment. This may provide a clue to answer the question. It is also
      found that survival is difficult for those species which cannot be entrained by
      the environmental cycle.

PMID- 12234752
TI  - HIV coreceptor usage and drug treatment.
AB  - The human immunodeficiency virus (HIV) infects a wide range of human cells. Cell
      entry is mediated through the CD4 receptor and a variety of coreceptors, most
      importantly the chemokine receptors CCR5 and CXCR4. Some antiretroviral agents
      selectively inhibit different HIV phenotypes depending on their coreceptor usage.
      Here, we analyse mathematical models, which describe the in vivo interaction of
      HIV phenotypes, differing in their coreceptor usage, with two target cell types
      (naive and memory CD4+ T cells). In particular, we investigate how the selection
      pressures on CCR5- and CXCR4-using HIV variants change as a result of treatment
      with coreceptor-specific antiretroviral agents. Our main result is that CXCR4
      inhibitors increase the selection pressure in favor of the emergence of CCR5
      using variants, thus selecting for coexistence of CXCR4- and CCR5-using variants,
      whereas CCR5 inhibitors increase the selection pressure against CCR5-using
      variants, thus selecting against coexistence. These results shed new light on the
      potential risks and benefits of coreceptor inhibitors.

PMID- 12234753
TI  - Functional consequences of nutrient translocation in mycelial fungi.
AB  - Fungi are of fundamental importance for plant and microbial nutrition with
      primary roles in decomposition and nutrient recycling. They also have great
      potential for use in areas of biotechnology such as bioremediation of organic and
      inorganic pollutants and biocontrol of plant pathogens. In all these contexts,
      environmental heterogeneity has a strong influence on growth and function. A
      large class of fungi overcome the difficulties encountered in such environments
      by the mechanism of translocation which results in the internal redistribution of
      nutrients within the fungal mycelium. In this paper, we use a combination of
      experimental techniques and mathematical modelling to examine fungal growth in
      general, and in particular, translocation in the common soil saprophytic fungus
      Rhizoctonia solani. A detailed mathematical model is presented where
      translocation is considered to have both diffusive and metabolically-driven
      components. A calibration experiment provided the necessary parameter values.
      Growth experiments were compared with model solutions and thus we provide strong
      evidence that diffusion is the dominant mechanism for translocation in
      homogeneous environments. In heterogeneous environments, we conclude that
      diffusion is still vital for exploration, i.e. the expansion of the fungal
      network into the surrounding area. However, we also conclude that localized
      resources may be utilized faster if energy is invested, i.e. when exploitation of
      the fungal microenvironment is enhanced by metabolically driven translocation.

PMID- 12234754
TI  - A study of the middle-scale nucleotide clustering in DNA sequences of various
      origin and functionality, by means of a method based on a modified standard
      deviation.
AB  - The deviation from randomness in the distribution of nucleotides in genomic
      sequences is quantified and studied, using a modified standard deviation (MSD).
      This method implies a "per block" computation of the standard deviation of the
      nucleotide frequencies of occurrence, using local means (means taken in a
      neighborhood of each block). This quantity may serve as a scale-dependent measure
      of the nucleotide clustering. In the present work, the meso-scale of tenths of
      nucleotides is principally explored, by means of suitably adjusted filter
      parameters. This length scale is of an order of magnitude not directly affected
      by the grammar and syntax rules of the protein-coding procedure, remaining
      shorter than the scale of appearance of large-scale characteristics of the
      genome. MSD has been found to distinguish systematically between the sequences of
      different origin and functionality. The most near-random are found to be coding
      sequences of prokaryotes, while in intronic and intergenic regions of eukaryotic
      genomes, extended clustering of similar nucleotides is observed. The
      distributions of MSD values of large collections of sequences are found to be in
      most cases characteristic of their biological role and origin. Protein- and non
      coding, prokaryotic and eukaryotic DNA as well as promoter, rRNA, viral and
      organelle sequences have been examined. The presented results corroborate a
      recently proposed model for genome evolution. The method is also applied for an
      assessment of the annotation of ORFs taken from the complete genome of
      Saccharomyces cerevisiae.

PMID- 12234755
TI  - On the dimerization of the primitive tRNAs: implications in the origin of genetic
      code.
AB  - RNAs that catalyse their own aminoacylation have been recently selected in vitro.
      These findings support the notion that the primitive aminoacyl-tRNA synthetases
      may have been RNAs. In this paper, we propose a structural model for the first
      aminoacyl-tRNA synthetase consisting of an RNA complex formed between two
      primitive tRNA molecules through two intermolecular loop-strand interactions, and
      with implications in the origin of the genetic code.

PMID- 12234756
TI  - Synchrony and heterochrony in ontogeny (of fish).
AB  - The ontogeny of an organism is a complex process that strongly depends on the
      timing of developmental processes. In this article, I discuss ontogeny of fish
      (and other organisms) in temporal terms, based on the hypothesis that organisms
      as self-organized entities may create their own times for their development, and
      that this development consists of a sequence of longer stabilized states (steps)
      with shorter, intermittent less-stable intervals (thresholds). If viewed within
      the context of structure-to-structure, organ-to-organ and/or organism-to
      environment relationships, then the saltatory pattern of ontogeny emerges at each
      transition from one stabilized state to another. I consider two timing mechanisms
      essential to ontogeny - synchrony (coordinating) and heterochrony (implementing);
      their possible roles are discussed. Besides this, a new context and understanding
      for the term heterochrony is proposed. At least three levels of heterochrony
      should be distinguished: interspecific, intraspecific and intraindividual.
      However, the difference among these three types of heterochrony is not in the
      phenomenon itself but in the way we perceive and classify it.

PMID- 12234757
TI  - Futile cycles revisited: a markov chain model of simultaneous glycolysis and
      gluconeogenesis.
AB  - We have used a random walk model of glycolysis and gluconeogenesis to investigate
      the bioenergetic implications of considering the cell cytoplasm to be a uniform
      well-mixed compartment. Radiotracer studies conducted on hepatocytes harvested
      from fasted rats and incubated with 40 mM glucose and 10 mM lactate demonstrated
      simultaneous glycolysis and gluconeogenesis, with net glycolysis. Tracer
      introduced as glycerol was incorporated both into glucose (via gluconeogenesis)
      and into pyruvate (via glycolysis). The data allow us to place a lower bound on
      the energetic cost of futile cycles involving adenosine triphosphate (ATP)
      hydrolysis in the early phosphorylation steps of glycolysis. Applying the Markov
      Chain model for glucose undergoing metabolism to pyruvate, the expected number of
      ATP molecules hydrolysed is not less than 15 ATP molecules per glucose molecule.
      The data suggest that, in hepatocytes under the circumstances of this experiment,
      either glycolysis is a net consumer of ATP, or glycolysis and gluconeogenesis are
      compartmentalized to a greater extent than is generally supposed.

PMID- 12234758
TI  - Frequency-dependent selection in sexual family-structured populations.
AB  - In this paper, a two-phenotype, single-locus, n -allele matrix game diploid model
      incorporating interactions between full sibs influencing personal fitness is
      investigated. Necessary and sufficient conditions for an ESS are given. We show
      that if a strategy is an ESS for this model with the payoff matrix A, then it
      must be an ESS for the standard game formulation with payoff matrix A+(r/2) A(T)
      where r is the probability to interact with a sib, but it is also possible that
      no ESS exists. Moreover, under the assumption of weak selection, the partial
      change in phenotype frequencies brings the population closer to an ESS when it
      exists.

PMID- 12234759
TI  - A lotka-volterra model of coexistence between a sexual population and multiple
      asexual clones.
AB  - At carrying capacity, small advantages in competitive ability can compensate a
      sexual population for its two-fold disadvantage in growth capacity when facing
      invasion by asexual mutants. In this paper, we develop a generic analytical model
      to consider the ecology of a sexual population comprising equal numbers of males
      and females, competing for shared prey resources with multiple female-only
      clones. We assume that the clones arise from the sexual population and are
      distinguished from it only by having narrower resource niches and twice the
      growth capacity. For sexual populations, at density-dependent carrying capacity,
      intra-specific competition between clonal individuals prevents them from
      realizing their two-fold advantage in intrinsic growth. This prediction leads to
      three novel outcomes: (i) a sexual population can coexist with any number of
      clones, provided their combined competitive impact remains less than the impact
      of the clones on each other; (ii) a sexual species can immediately exclude
      asexual invaders if it is a fast growing and strong competitor of shared
      resources and also has refuge in an abundant alternative resource; (iii) the rate
      of accumulation of clones in a sexual population will be slowed by intra and
      inter-specific competition amongst the clones themselves, in addition to the
      competitive impact from the original sexual population.

PMID- 12234760
TI  - Introduction.

PMID- 12234761
TI  - Calcium cycling, historic overview and perspectives. Role for autonomic nervous
      system regulation.
AB  - The human heart proceeds from a relaxed state (diastole) to a fully contracted
      state (systole) and recovery in 600ms. During this period, Ca(2+) inside the
      myocardial cell rises from about 10nM to about 100nM and returns to the former.
      The contractile-relaxation cycle is tightly coupled to the Ca(2+)transient. In
      the normal physiological state, the autonomic nervous system (ANS) plays a major
      role in the regulation of cardiac function and important changes occur in
      diseases of the heart. Sympathetic overdrive is a major determinant of the
      critical transition from initial compensatory hypertrophy to decompensated
      failure. Cardiac myocytes from failing hearts are characterized by a number of
      abnormalities in excitation-contraction coupling, that are a direct consequence
      of beta-adrenergic signaling defects. Although desensitized in cardiac
      hypertrophy and failure, the beta-adrenergic signaling pathway retains receptor
      capacity, a characteristic that is used in therapeutic approaches. There are
      several putative Ca(2+)-dependent pathways that exert counterbalancing negative
      regulation over cAMP-dependent positive inotropic effect and may represent
      potential targets for contractile stimulation. This review is focused on the
      interactions between sympathetic drive and aspects of calcium signaling in the
      heart.

PMID- 12234762
TI  - Structure-function relationships in Ca(2+) cycling proteins.

PMID- 12234763
TI  - Calcium, calmodulin, and calcium-calmodulin kinase II: heartbeat to heartbeat and
      beyond.
AB  - Calcium (Ca) is the key regulator of cardiac contraction during excitation
      contraction (E-C) coupling. However, differences exist between the amount of Ca
      being transported into the myocytes upon electrical stimulation as compared to Ca
      released from the sarcoplasmic reticulum (SR). Moreover, alterations in E-C
      coupling occur in cardiac hypertrophy and heart failure. In addition to the
      direct effects of Ca on the myofilaments, Ca plays a pivotal role in activation
      of a number of Ca-dependent proteins or second messengers, which can modulate E-C
      coupling. Of these proteins, calmodulin (CaM) and Ca-CaM-dependent kinase II
      (CaMKII) are of special interest in the heart because of their role of modulating
      Ca influx, SR Ca release, and SR Ca uptake during E-C coupling. Indeed, CaM and
      CaMKII may be associated with some ion channels and Ca transporters and both can
      modulate acute cellular Ca handling. In addition to the changes in Ca, CaM and
      CaMKII signals from beat-to-beat, changes may occur on a longer time scale. These
      may occur over seconds to minutes involving phosphorylation/dephosphorylation
      reactions, and even a longer time frame in altering gene transcription
      (excitation-transcription (E-T) coupling) in hypertrophic signaling and heart
      failure. Here we review the classical role of Ca in E-C coupling and extend this
      view to the role of the Ca-dependent proteins CaM and CaMKII in modulating E-C
      coupling and their contribution to E-T coupling.

PMID- 12234764
TI  - Local Ca(2+) signaling and EC coupling in heart: Ca(2+) sparks and the regulation
      of the [Ca(2+)](i) transient.
AB  - The elementary event of Ca(2+) release in heart is the Ca(2+) spark. It occurs at
      a low rate during diastole, activated only by the low cytosolic [Ca(2+)](i).
      Synchronized activation of many sparks is due to the high local [Ca(2+)](i) in
      the region surrounding the sarcoplasmic reticulum (SR) Ca(2+) release channels
      and is responsible for the systolic [Ca(2+)](i) transient. The biophysical basis
      of this calcium signaling is discussed. Attention is placed on the local
      organization of the ryanodine receptors (SR Ca(2+) release channels, RyRs) and
      the other proteins that underlie and modulate excitation-contraction (EC)
      coupling. A brief review of specific elements that regulate SR Ca(2+) release
      (including SR lumenal Ca(2+) and coupled gating of RyRs) is presented. Finally
      integrative calcium signaling in heart is presented in the context of normal
      heart function and heart failure.

PMID- 12234766
TI  - On Koch's postulates, causality and genetics of cardiomyopathies.

PMID- 12234765
TI  - Calcium cycling in congestive heart failure.

PMID- 12234767
TI  - Frequency-dependent acceleration of relaxation in the heart depends on CaMKII,
      but not phospholamban.
AB  - Frequency-dependent acceleration of relaxation (FDAR) is an intrinsic
      physiological mechanism, which allows more rapid ventricular diastolic filling at
      higher heart rates. FDAR is also observed in isolated myocardial trabeculae and
      cardiac myocytes, but its mechanism is still poorly understood. We tested the
      hypothesis that FDAR results mainly from Ca/calmodulin-dependent protein kinase
      II (CaMKII) dependent stimulation of sarcoplasmic reticulum (SR) Ca transport,
      but does not require phospholamban. Experiments were performed at 23 or 35
      degrees C in isolated ventricular muscle and single myocytes from wild-type (WT)
      and phospholamban knockout (PLB-KO) mice and rat ventricular myocytes. Isometric
      twitch force of muscles and unloaded shortening and Ca transients in myocytes
      were measured ([Ca](o)=1mM) in the absence and presence of CaMKII inhibitors (1
      microM KN-93 or 20 microM autocamtide-2 related inhibitory peptide, AIP).
      Stimulation frequency was altered over a wide range (0.2-8Hz) and post-rest vs
      steady state twitches were also compared. In both WT and PLB-KO mouse muscles
      FDAR of twitch force was prominent, but was largely suppressed by KN-93. FDAR of
      twitch contractions was associated with FDAR of Ca transients in PLB-KO myocytes,
      and both were inhibited by KN-93. Similarly, a different CaMKII inhibitor (AIP)
      inhibited FDAR of contraction and Ca transients in rat ventricular myocytes. We
      conclude that FDAR results mainly from CaMKII-dependent stimulation of SR Ca
      transport, but does not require phospholamban.

PMID- 12234768
TI  - Depressed PKA activity contributes to impaired SERCA function and is linked to
      the pathogenesis of glucose-induced cardiomyopathy.
AB  - We have previously described a cardiomyopathy induced by culturing ventricular
      myocytes from normal adult rats in a medium containing high concentrations of
      glucose, which recapitulates cellular changes associated with early onset
      diabetic cardiomyopathy. This investigation was designed to evaluate cellular
      mechanisms that could contribute to slowed cytosolic Ca(2+) removal and myocyte
      relaxation in glucose-induced cardiomyopathy. Isolated ventricular myocytes were
      cultured overnight in medium containing normal glucose (n=5.5mM) or high glucose
      (HG=25.5mM). Cytosolic Ca(2+) removal was monitored with fluo-3 and myocyte
      mechanics with video-edge detection. Electrically stimulated Ca(2+) transients
      were prolonged in HG cells (A(T/PK)=215+/-7ms, n=41) compared to N myocytes
      (A(T/PK)=173+/-5ms, n=34). By pharmacological and ionic manipulations, Ca(2+)
      removal attributable to SERCA was slower in the HG group (A(D/PK)=290+/-17ms,n
      =41) compared to N (A(D/PK)=219+/-10, n=34), whereas NCX function was similar in
      both groups of cells. Total PKA activity was depressed in HG myocytes by 56%
      compared to N cells. beta-adrenergic receptor stimulation with ISO (10(-7)M)
      normalized myocyte relaxation, Ca(2+) transients and PKA activity in HG myocytes.
      Furthermore, inhibition of PKA with H89 (10(-5)M) depressed peak fractional
      shortening (PS) and slowed relengthening (A(R/PK)) to a greater extent in N (-50%
      for PS and 92% for A(R/PK)) than in HG cells (-25% for PS and 48% A(R/PK)).
      Depressed cytosolic Ca(2+) removal was not, however, associated with changes in
      basal levels of phosphorylated PLB, nor levels of SERCA, NCX or PLB proteins. We
      conclude that cellular mechanisms associated with the early onset glucose-induced
      cardiomyocyte dysfunction involves alterations in Ca(2+) regulation, which may be
      a common manifestation of other forms of cardiomyopathies.

PMID- 12234769
TI  - Cellular thiols redox status: a switch for NF-kappaB activation during myocardial
      post-ischaemic reperfusion.
AB  - Myocardial ischaemia/reperfusion induces NF-kappaB activation, but little is
      known about the stimuli through which it occurs. Aims of the study were to
      investigate whether: (a) oxidative stress induced by ischaemia/reperfusion is
      linked with NF-kappaB activation; (b) counteraction of oxidative stress by N
      acetyl cysteine (NAC) reduces NF-kappaB activation. At this purpose, in isolated
      rat hearts, we induced mild (15 min) and severe (30 min) ischaemia; a group of
      the hearts submitted to severe ischaemia were treated with NAC. Our data indicate
      that reperfusion after severe ischaemia activates NF-kappaB: the presence of p65
      in the nuclear extracts was 274.5+/-18.6% vs aerobia; (P<0.05) and an induced DNA
      binding activity was detected. NF-kappaB translocation occurs in parallel with
      myocardial decrease in reduced glutathione and protein -SH (from 9.2+/-0.4 to
      5.4+/-0.3 nmol/mg prot, P<0.01, and from 350.3+/-16.6 to 296.0+/-9.1 nmol/mg
      prot, P<0.05) and accumulation of oxidised glutathione-GSSG-(from 0.075+/-0.005
      to 0.118+/-0.007 nmol/mg prot, P<0.01). When ischaemia/reperfusion does not
      result in any oxidative stress (in mild ischaemia or severe ischaemia plus NAC),
      NF-kappaB does not translocate. A significant correlation was found between the
      activation of NF-kappaB and the accumulation of GSSG in the myocardium. Our data
      indicate that an oxidative shift of cellular thiolic pools can modulate the genic
      transcription of the heart through NF-kappaB activation.

PMID- 12234770
TI  - Alpha(1)-adrenoceptor subtypes mediate negative inotropy in myocardium from
      alpha(1A/C)-knockout and wild type mice.
AB  - Cardiac alpha(1)-adrenoceptors (AR) have two predominant subtypes (alpha(1A)-AR
      and alpha(1B)-AR) however, their roles in regulating contraction are unclear. We
      determined the effects of stimulating alpha(1A)-AR (using the subtype-selective
      agonist A61603) and alpha(1B)-AR (using a gene knockout mouse lacking alpha(1A)
      AR) separately, and together (using phenylephrine) on Ca(2+) transients,
      intracellular pH, and contraction of mouse cardiac trabeculae. Stimulation of
      alpha(1)-AR subtypes separately or together caused a triphasic contractile
      response. After a transient ( approximately 3%) force rise (phase 1), force
      declined markedly (phase 2), then partially recovered (phase 3). In phase 2, the
      force decline (% of initial) with combined alpha(1A)-AR plus alpha(1B)-AR
      stimulation (50+/-3%) was more than with separate subtype stimulation (P<0.01),
      suggesting alpha(1A)-AR and alpha(1B)-AR mediate additive effects during phase 2.
      Force decline in phase 2 paralleled decreases of Ca(2+) transients that were
      reduced more with combined vs. separate subtype stimulation. During phase 3 the
      final force reduction was similar with stimulation of alpha(1A)-AR (20+/-5%), or
      alpha(1B)-AR (20+/-3%), or both (26+/-4%) suggesting alpha(1A)-AR and alpha(1B)
      AR mediate non-additive effects during phase 3. In contrast, Ca(2+) transients
      recovered fully in phase 3 suggesting reduced force in phase 3 involved decreased
      myofilament Ca(2+)-sensitivity. Decreased Ca(2+)-sensitivity was not mediated by
      changes of intracellular pH since this was not affected by alpha(1)-AR
      stimulation. In contrast to mouse trabeculae, rat trabeculae demonstrated a
      positive inotropic response to alpha(1)-AR stimulation. In conclusion, for mouse
      myocardium in vitro both alpha(1)-adrenoceptor subtypes mediate negative inotropy
      involving decreased Ca(2+) transients and a decreased Ca(2+) sensitivity that
      does not involve altered intracellular pH.

PMID- 12234771
TI  - Dissociation of stress-activated protein kinase (p38-MAPK and JNKs)
      phosphorylation from the protective effect of preconditioning in vivo.
AB  - The aim of the present study was to examine and compare the role of the stress
      activated protein kinases in ischemic and stretch-induced preconditioning. A
      model of anesthetized rabbits was used, and the preconditioning protocol included
      one or three cycles of short ischemia/reperfusion, or short mechanical stretch
      with acute pressure overload without or with the addition of the stretch blocker
      gadolinium. Infarct size was determined after 2h reperfusion and p38 MAPK and
      JNKs phosphorylation was determined after 20 min of prolonged ischemia.
      Preconditioning stimuli were equally effective in reducing the infarct size
      (14.2+/-3.4%, 12.9+/-3.0%, 15.9+/-3.3%, P<0.01 vs control). The addition of the
      stretch channel blocker gadolinium abrogated the effect of stretch
      preconditioning only, without any effect on ischemic preconditioning. Comparing
      p38-MAPK and p46/p54 JNKs phosphorylation in the ischemic and non-ischemic
      regions of the heart at the time of sustained ischemia, activation was observed
      in the ischemic or mechanically preconditioned groups compared with the control.
      The addition of gadolinium abolished this activation. The above results indicate
      that the phosphorylation of p38-MAPK and p46/p54 JNKs is increased in
      preconditioning but this effect can be dissociated from the protective effect of
      ischemic preconditioning. Activation of the stress-activated protein kinases may
      be related to the increased contracture, a characteristic of ischemic
      preconditioning.

PMID- 12234772
TI  - Late Na currents affected by alpha subunit isoform and beta1 subunit co
      expression in HEK293 cells.
AB  - Peak Na current underlies excitability and conduction in the heart, and late non
      inactivating or slowly inactivating Na current plays a role in action potential
      duration. We hypothesized that different alpha subunit isoforms or beta1 subunit
      co-expression might affect late Na current. The human Na channel alpha subunits
      hNa(v)1.5 (hH1a) and hNa(v)1.4 (hSkM1) were transfected with and without the
      hNa(V)beta1 (beta1) subunit in HEK293 cells and studied by whole cell patch
      clamp. The inactivation relationship for hH1a was 28mV negative to that for
      hSkM1, and beta1 shifted the midpoint positively by 22mV for hH1a and 8mV for
      hSkM1. When pre-pulse duration was varied from 10ms to 10s, "steady-state" was
      approached more slowly for hH1a. beta1 caused hH1a but not hSkM1 to reach "steady
      state" earlier. Both isoforms showed two recovery components but hH1a showed a
      "cardiac phenotype" with a smaller slow component that was unaffected by beta1.
      The amplitude of a late current (at 750ms) was significantly greater for hH1a
      than hSkM1, but beta1 decreased late current for hH1a and eliminated the
      difference. Under the study conditions the alpha subunit isoforms have distinct
      functional phenotypes and co-expression with beta1 tends to diminish these
      distinctions. These properties may provide mechanisms for regional and transmural
      distribution of late Na current and late Na current amplitudes during development
      and in disease states.

PMID- 12234773
TI  - L-nitro-arginine inhibits increase in endothelin binding sites induced by
      ischemia and reperfusion.
AB  - We have demonstrated that ischemia and reperfusion promoted augmented contractile
      response to endothelin-1 (ET) in coronary arteries in the presence of
      polymorphonuclear leukocytes (PMN). It has been also reported that ischemia and
      reperfusion increase ET binding sites in cardiac membrane in isolated rat heart
      perfused by blood cell-free system. To determine the role of PMN and L-arginine
      to nitric oxide (NO) pathway in these phenomena, isolated perfused rabbit hearts
      were subjected to 30 min of global ischemia followed by 30 min of reflow in the
      absence or presence of PMN and 10(-5)M of L-nitro-arginine (LNA). PMN was
      prepared with Percoll density gradients from peritoneal exudate elicited by
      glycogen. PMN activated with 10(-6)M of phorbol myristate acetate or their
      supernatant were infused into the coronary perfusion circuit after 5 min of
      reflow. LNA was added to perfusate also after reflow. The effect of superoxide
      dismutase (SOD: 50 IU/ml) was also determined. After the end of protocols,
      membrane fraction was isolated from the hearts for (125)I-ET-1 binding assay. ET
      1 binding (Bmax) showed a significant increase by ischemia and reperfusion
      (P<0.01 vs control). That was markedly augmented with addition of activated PMN
      or their supernatant (both P<0.01), but abolished either by LNA or SOD (P<0.01
      and P<0.05, respectively). These results indicate that increase in ET-receptor by
      ischemia and reperfusion is mediated by free radicals generated via L-arginine to
      NO pathway.

PMID- 12234774
TI  - Nitric oxide induces caspase-dependent apoptosis and necrosis in neonatal rat
      cardiomyocytes.
AB  - Excessive nitric oxide (NO) production has been implicated in the pathophysiology
      of cardiomyocyte (CMC) apoptosis and necrosis induced by ischemia/reperfusion,
      inflammation and NO-donating chemicals. Although caspases are known to be
      involved in apoptosis, the present study examined whether caspases also play a
      role in NO-induced CMC necrosis. Neonatal rat CMCs were labeled with Annexin-V
      and propidium iodide, and apoptosis and necrosis were analyzed by confocal images
      and fluorescence activated cell sorter analysis. CMC apoptosis and necrosis were
      also evaluated by determining DNA fragmentation in the cell and the supernatant
      fractions. Treatment of CMCs with the NO donor, diethylenetriamine NO (DETA/NO)
      or S-nitroso-N-acetyl-penicillamine (SNAP) at concentrations of 10 and 100 microM
      for 24h induced predominantly apoptosis over necrosis, but a higher concentration
      (1mM) of DETA/NO or SNAP provoked both apoptosis and necrosis. The lower doses of
      DETA/NO-induced apoptosis was associated with a gradual increase in caspase-3
      activity over 24h without appreciable activation of poly ADP-ribose polymerase
      (PARP), while the higher dose of DETA/NO induced a marked increase in caspase-3
      activity and CMC apoptosis until 2h after the treatment, and increased necrotic
      CMCs thereafter associated with robust activation of PARP. The caspase inhibitor
      Z-DEVD-FMK but not the poly ADP-ribose polymerase (PARP) inhibitor 3
      aminobenzamide (3-AB) abolished caspase-3 activation and CMC apoptosis induced by
      100 microM DETA/NO. However, both Z-DEVD-FMK and 3-AB abolished PARP activation
      and CMC necrosis induced by 1mM DETA/NO. The amount of nicotinamide adenine
      dinucleotide (NAD) and adenine nucleotides in CMCs was not significantly affected
      by treatment with 10 and 100 microM DETA/NO, but was significantly reduced by
      treatment with 1mM DETA/NO without a decline of adenylate energy charge. The
      depletion of NAD and adenine nucleotides was abrogated by Z-DEVD-FMK and 3-AB.
      These results suggest that caspase activation play a crucial role in CMC
      apoptosis induced by lower concentrations of NO as well as in CMC necrosis
      induced by a higher concentration of and a longer exposure to NO. NO-induced CMC
      necrosis is likely mediated by PARP activation which occurs as a consequence of
      caspase activation.

PMID- 12234775
TI  - Glucose uptake and adenoviral mediated GLUT1 infection decrease hypoxia-induced
      HIF-1alpha levels in cardiac myocytes.
AB  - Hypoxia causes a large array of adaptive and physiological responses in all cells
      including cardiac myocytes. In order to elucidate the molecular effects of
      increased glucose flux on hypoxic cardiac myocytes we focused on the basic helix
      loop-helix transcription factor, hypoxia inducible factor 1 alpha (HIF-1alpha),
      which is rapidly upregulated in hypoxic cells and elicits a number of responses
      including augmentation of glucose uptake. Primary cultures of neonatal rat
      cardiac myocytes as well as embryonic rat heart-derived myogenic H9c2 cells
      demonstrated a significant upregulation of HIF-1alpha when subjected to hypoxia
      of 6-8h in the absence of glucose. Re-addition of extracellular glucose to the
      medium resulted in a decrease of HIF-1alpha levels by almost 50%. This glucose
      effect was blocked by addition of glycolytic inhibitors. In addition, glucose
      uptake and glycolysis resulted in substantial decreased levels of p53, which is
      regulated by HIF-1alpha. Adenoviral infection of cultures of cardiac myocytes
      with the facilitative glucose transporter, GLUT1 followed by hypoxia of 24h also
      resulted in a significant reduction in the protein expression of HIF-1alpha
      compared to control vector-infected cultures. GLUT1 infected cultures also
      demonstrated fewer apoptotic cells and a reduction in the release of cytochrome c
      after hypoxia. Inhibition of the ubiquitin-proteasomal pathway by a variety of
      26S proteasomal inhibitors increased HIF-1alpha to similar levels under both
      normoxic and hypoxic conditions and in the presence or absence of glucose. This
      result suggested that glucose induces HIF-1alpha degradation via a proteasomal
      pathway. This conclusion was substantiated by immunoprecipitation experiments of
      total cell extracts, which demonstrated an increase of ubiquitinated HIF-1alpha
      relative to total HIF-1alpha in the presence of glucose during hypoxia. Thus,
      glucose as well as GLUT1 overexpression diminishes hypoxia-induced HIF-1alpha
      protein via an ubiquitin-proteasomal pathway in hypoxic cardiac myocytes. This
      represents a novel feedback mechanism that may play an important role in
      adaptation of cardiac myocytes to hypoxia and ischemia.

PMID- 12234776
TI  - The mechanism of excitation-contraction coupling in phenylephrine-stimulated
      human saphenous vein.
AB  - The human saphenous vein (HSV) is the most widely used graft in coronary artery
      revascularization procedures and is susceptible to spasm perioperatively. The aim
      of this study is to elucidate the mechanism(s) of agonist-induced excitation
      contraction coupling in this vessel. Isometric contraction experiments were
      combined with in situ smooth muscle intracellular Ca(2+) concentration
      ([Ca(2+)](i)) imaging by confocal microscopy of intact undistended HSV segments
      during activation with phenylephrine (PE; 50 microM). Stimulation with PE
      produced a sustained contraction. Preincubation with 5 microM nifedipine, a
      blocker of the L-type voltage-operated Ca(2+) channel, or 50 microM SKF-96365, a
      blocker of both the voltage- and receptor-operated channels, reduced force
      generation by 25-30%. Ca(2+) imaging revealed that PE elicited only a transient
      rise in [Ca(2+)](i), suggesting that Ca(2+) plays only a minor role. However, a
      requirement for basal Ca(2+) levels was demonstrated when PE contractions could
      not be maintained in Ca(2+)-free medium. In light of the transient Ca(2+)
      response, it appears that signals other than Ca(2+) must maintain the tonic
      contraction elicited by PE, such as those that sensitize the myofilaments to
      Ca(2+). Application of HA-1077 (a Rho kinase inhibitor) at the peak of the
      contraction completely abolished the plateau phase of the response, whereas
      application of genistein (a tyrosine kinase inhibitor) reduced this phase by
      approximately 50%. The foregoing results suggest that, whereas the transient
      Ca(2+) signal can contribute to the development of force, maintenance of the
      plateau phase of the PE contraction in the HSV is the result of myofilament
      Ca(2+) sensitization by Rho kinase and tyrosine phosphorylation. The elucidation
      of the mechanisms of excitation-contraction coupling in the HSV may be useful for
      the development of therapeutic strategies for the alleviation of vein graft
      spasm.

PMID- 12234777
TI  - Role of glycocalyx in leukocyte-endothelial cell adhesion.
AB  - The binding of fluorescently labeled microspheres (FLMs, 0.1-microm diameter)
      coated with antibody (1a29) to ICAM-1 was studied in postcapillary venules during
      topical application of the chemoattractant N-formylmethionyl-leucyl-phenylalanine
      (fMLP). FLM adhesion to endothelial cells (ECs) increased dramatically from 50 to
      150 spheres per 100-microm length of venule after superfusion of the mesentery
      with fMLP and equaled or exceeded levels of leukocyte (WBC) adhesion. Removal of
      the EC glycocalyx by micropipette infusion of the venule with heparinase
      increased FLM-EC adhesion to levels attained with fMLP. Subsequent application of
      fMLP did not increase FLM adhesion further, suggesting that the FLMs saturated
      all ICAM-1 binding sites. Perfusion with heparinase after suffusion with fMLP
      significantly increased FLM-EC adhesion above levels attained with fMLP. However,
      WBC adhesion fell because of possible removal of selectins necessary to maintain
      WBC rolling at the wall. It is concluded that the glycocalyx serves as a barrier
      to adhesion and that its shedding during natural activation of ECs may be an
      essential part of the inflammatory response.

PMID- 12234778
TI  - Comparison of effects of two hemoglobin-based O(2) carriers on intestinal
      integrity and microvascular leakage.
AB  - Two "blood substitutes," a diaspirin cross-linked human hemoglobin [bis(3,5
      dibromosalicyl)fumarate, DBBF-Hb] and a bovine polymerized hemoglobin (PolyHbBv),
      advanced to clinical trials, are used in this study. Previously, we have shown
      that injection of DBBF-Hb into the rat circulation produces venular leakage and
      intestinal epithelial disruption. The purpose of this study was to determine
      whether PolyHbBv, currently approved for veterinary use in the United States,
      shows similar effects. In anesthetized Sprague-Dawley rats, the mesenteric
      microvasculature was perfused with DBBF-Hb (n = 6), PolyHbBv (n = 5), cyanomet Hb
      (CNmet-DBBF-Hb), or HEPES-buffered saline with 0.5% bovine serum albumin (HBS
      BSA) (controls, n = 7) for 10 min, followed by FITC-albumin for 3 min, and then
      fixed for microscopy. For DBBF-Hb, the mean leak number per micrometer venule
      length [2.41 +/- 0.33 (+/-SE) x 10(-3)] was significantly greater than for
      PolyHbBv (0.53 +/- 0.14 x 10(-3)), CNmet-DBBF-Hb (0.36 +/- 0.14 x 10(-3)), and
      HBS-BSA (0.12 +/- 0.08 x 10(-3)) (P < 0.01). Corresponding quantities for leak
      area were 0.10 +/- 0.03, 0.010 +/- 0.003, 0.005 +/- 0.003, and 0.02 +/- 0.02
      microm(2)/microm. In rats injected with DBBF-Hb (n = 8), intestinal epithelial
      integrity was significantly compromised compared with those injected with
      PolyHbBv (n = 5) or saline (n = 6). These results indicate that intravascular
      PolyHbBv produces significantly less disruption of the intestinal exchange
      barrier than does DBBF-Hb, probably because the heme is not so easily oxidized.

PMID- 12234779
TI  - Influence of posture on left ventricular long- and short-axis shortening.
AB  - End-diastolic volume and left ventricular stroke volume are increased in the
      supine compared with upright position, but the contribution of long-axis (LAS)
      and short-axis shortening (SAS) to these changes with change in posture has not
      been established. We examined long- and short-axis motion and dimensions with
      echocardiography in 10 healthy subjects in the upright and supine position. Long
      axis length at end diastole was almost identical, whereas the diastolic short
      axis diameter was increased in the supine position. At end systole, there was a
      decreased long-axis length and increased short-axis length in the supine vs.
      upright position. Both LAS and SAS were enhanced in supine vs. upright positions
      [LAS: 9.3 +/- 2.2 vs. 15.1 +/- 3.1 mm (P < 0.001); SAS: 12.7 +/- 3.2 vs. 16.3 +/-
      2.8 mm (P < 0.001)], presumably via Starling mechanisms. LAS increased more in
      the lateral part of the mitral annulus than in the septal part [7.7 +/- 2.6 vs.
      4.0 +/- 2.8 mm (P < 0.006)], which implies that the more spherical form, in the
      supine position, induces more stretch at the lateral free wall than in the
      ventricular septum. These findings support the notion that Starling mechanisms
      affect systolic LAS.

PMID- 12234780
TI  - Adenosine A(3) receptor activation protects the myocardium from
      reperfusion/reoxygenation injury.
AB  - Ischemia-reperfusion induces both necrotic and apoptotic cell death. The ability
      of adenosine to attenuate reperfusion-induced injury (RI) and the role played by
      adenosine receptors are unclear. We therefore studied the role of the A(3)
      receptor (A(3)R) in ameliorating RI using the specific A(3)R agonist 1-[2-chloro
      6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxi-N-methyl-b-D
      ribofuranuronamide (2-Cl-IB-MECA). Isolated rat hearts and cardiomyocytes were
      subjected to ischemia or simulated ischemia, followed by
      reperfusion/reoxygenation. The end points were percent infarction/risk zone and
      annexin-V (apoptosis) and/or propidium iodide positivity (necrosis),
      respectively. In isolated hearts, 2-Cl-IB-MECA significantly limited infarct size
      (44.2 +/- 2.7% in control vs. 21.9 +/- 2.4% at 1 nM and 35.8 +/- 3.3% at 0.1 nM,
      P < 0.05). In isolated myocytes, apoptosis and necrosis were significantly
      reduced compared with controls (5.7 +/- 2.6% vs. 17.1 +/- 1.3% and 13.7 +/- 2.0%
      vs. 23.1 +/- 1.5%, respectively, P < 0.0001). In both models, the beneficial
      effects were abrogated using the A(3)R antagonist MRS-1191. The involvement of
      A(2a) receptor activation was also examined. This is the first study to
      demonstrate that A(3)R activation at reperfusion limits myocardial injury in the
      isolated rat heart and improves survival in isolated myocytes, possibly by
      antiapoptotic and antinecrotic mechanisms.

PMID- 12234781
TI  - Antiadrenergic effects of adenosine A(1) receptor-mediated protein phosphatase 2a
      activation in the heart.
AB  - The ability of adenosine A(1) receptors to activate type 2a protein phosphatase
      (PP2a) and account for antiadrenergic effects was investigated in rat myocardial
      preparations. We observed that the adenosine A(1) receptor agonist N(6)
      cyclopentyladenosine (CPA) significantly reduces the isoproterenol-induced
      increase in left ventricular developed pressure of isolated heats, and this
      effect is blocked by pretreatment of hearts with the PP2a inhibitor cantharidin.
      CPA alone or given in conjunction with isoproterenol stimulation decreases
      phosphorylation of phospholamban and troponin I in ventricular myocytes. These
      dephosphorylations are blocked by an adenosine A(1) receptor antagonist and by
      PP2a inhibition with okadaic acid. Adenosine A(1) receptor activation was also
      shown to increase carboxymethylation of the PP2a catalytic subunit (PP2a-C) and
      cause translocation of PP2a-C to the particulate fraction in ventricular
      myocytes. These results support the hypothesis that adenosine A(1) receptor
      activation leads to methylation of PP2a-C and subsequent translocation of the
      PP2a holoenzyme. Increases in localized PP2a activity lead to dephosphorylation
      of key cardiac proteins responsible for the positive inotropic effects of beta
      adrenergic stimulation.

PMID- 12234782
TI  - HSC73-tubulin complex formation during low-flow ischemia in the canine
      myocardium.
AB  - Canine myocardium was exposed to bouts of low-flow ischemia to identify the
      interactions that develop between the microtubule-based cytoskeleton and the heat
      shock protein 70 (HSP70) family of heat shock proteins in viable cardiomyocytes.
      "Moderate" or "severe" low-flow ischemia was produced in chronically instrumented
      dogs by reducing circumflex coronary flow by 50% for 2 h or by 75% for 5 h
      followed by reperfusion for 2 and 24 h, respectively. Electron and
      immunofluorescence microscopy demonstrated either partial or nearly complete
      depolymerization of the intermyofibrillar microtubules in areas of myofibril
      disruption and partial dissolution of the perinuclear microtubule girdle. In
      contrast, centrosomal tubulin arrays appeared to remain intact following low-flow
      ischemia. In cardiomyocytes displaying myofibril disruption, constitutively
      expressed HSP73 (HSC73) colocalized with intact but not disrupted microtubules
      and with perinuclear and centrosomal tubulin following moderate ischemia.
      Microtubule depolymerization and high molecular weight tubulin-HSC73 complexes
      were present in more severely ischemic tissue. These results suggest that HSC73
      directly interacts with tubulin and may protect selected elements of the
      microtubule network and limit myofibril disruption during reversible low-flow
      ischemia.

PMID- 12234783
TI  - Altered function in atrium of transgenic mice overexpressing triadin 1.
AB  - Triadin 1 is a protein in the cardiac junctional sarcoplasmic reticulum (SR) that
      interacts with the ryanodine receptor, junctin, and calsequestrin, proteins that
      are important for Ca(2+) release. To better understand the role of triadin 1 in
      SR-Ca(2+) release, we studied the time-dependent expression of SR proteins and
      contractility in atria of 3-, 6-, and 18-wk-old transgenic mice overexpressing
      canine cardiac triadin 1 under control of the alpha-myosin heavy chain (MHC)
      promoter. Three-week-old transgenic atria exhibited mild hypertrophy. Finally,
      atrial weight was increased by 110% in 18-wk-old transgenic mice. Triadin 1
      overexpression was accompanied by time-dependent changes in the protein
      expression of the ryanodine receptor, junctin, and cardiac/slow-twitch muscle SR
      Ca(2+)-ATPase isoform. Force of contraction was already decreased in 3-wk-old
      transgenic atria. The application of caffeine led to a positive inotropic effect
      in transgenic atria of 3-wk-old mice. Rest pauses resulted in an increased
      potentiation of force of contraction after restimulation in 3- and 6-wk-old mice
      and a reduced potentiation of force of contraction in 18-wk-old transgenic mice.
      Hence, triadin 1 overexpression triggered time-dependent alterations in SR
      protein expression, Ca(2+) homeostasis, and contractility, indicating for the
      first time an inhibitory function of triadin 1 on SR-Ca(2+) release in vivo.

PMID- 12234784
TI  - Tropomyosin 3 expression leads to hypercontractility and attenuates myofilament
      length-dependent Ca(2+) activation.
AB  - Tropomyosin (TM), an integral component of the thin filament, is encoded by three
      striated muscle isoforms: alpha-TM, beta-TM, and TPM 3. Although the alpha-TM and
      beta-TM isoforms are well characterized, less is known about the function of the
      TPM 3 isoform, which is predominantly found in the slow-twitch musculature of
      mammals. To determine its functional significance, we ectopically expressed this
      isoform in the hearts of transgenic mice. We generated six transgenic mouse lines
      that produce varying levels of TPM 3 message with ectopic TPM 3 protein
      accounting for 40-60% of the total striated muscle tropomyosin. The transgenic
      mice have normal life spans and exhibit no morphological abnormalities in their
      sarcomeres or hearts. However, there are significant functional alterations in
      cardiac performance. Physiological assessment of these mice by using closed-chest
      analyses and a work-performing model reveals a hyperdynamic effect on systolic
      and diastolic function. Analysis of detergent-extracted fiber bundles
      demonstrates a decreased sensitivity to Ca(2+) in force generation and a decrease
      in length-dependent Ca(2+) activation with no detectable change in interfilament
      spacing as determined by using X-ray diffraction. Our data are the first to
      demonstrate that TM isoforms can affect sarcomeric performance by decreasing
      sensitivity to Ca(2+) and influencing the length-dependent Ca(2+) activation.

PMID- 12234785
TI  - Effect of cardiac pacing on forearm vascular responses and nitric oxide function.
AB  - We examined the hypothesis that changes in heart rate at rest influence
      bioactivity of nitric oxide (NO) in humans by examining forearm blood flow
      responses during cardiac pacing in six subjects. Peak forearm and mean forearm
      blood flows across the cardiac cycle were continuously recorded at baseline and
      during pacing, with the use of high-resolution brachial artery ultrasound and
      Doppler flow velocity measurement. The brachial artery was cannulated to allow
      continuous infusion of saline or N(G)-monomethyl-L-arginine (L-NMMA). As heart
      rate increased, no changes in pulse pressure and mean or peak blood flow were
      evident. L-NMMA had no effect on brachial artery diameter, velocity, or flows
      compared with saline infusion. These results contrast with our recent findings
      that exercise involving the lower body, associated with increases in heart rate
      and pulse pressure, also increased forearm blood flow, the latter response being
      diminished by L-NMMA. These data suggest that changes in blood pressure, rather
      than pulse frequency, may be the stimulus for shear stress-mediated NO release in
      vivo.

PMID- 12234786
TI  - Acute and chronic NOS inhibition enhances alpha(2)- adrenoreceptor-stimulated
      RhoA and Rho kinase in rat aorta.
AB  - We demonstrated that arteries from rats made hypertensive with chronic nitric
      oxide (NO) synthase (NOS) inhibition (N(omega)-nitro-L-arginine in drinking
      water, LHR) have enhanced contractile sensitivity to alpha(2)-adrenergic
      receptors (alpha(2)-AR) agonist UK-14304 compared with arteries from normotensive
      rats (NR). NO may regulate vascular tone in part through suppression of RhoA and
      Rho kinase (ROK). We hypothesized that enhanced RhoA and ROK activity augments
      alpha(2)-AR contraction in LHR aortic rings. Y-27632 eliminated UK-14304
      contraction in LHR and NR aortic rings. The order of increasing sensitivity to Y
      27632 was the following: endothelium-intact NR, LHR, and endothelium-denuded NR.
      UK-14304 stimulated RhoA translocation to the membrane fraction in LHR and
      denuded NR but not in intact NR aorta. Basally, more RhoA was present in the
      membrane fraction in denuded NR than in intact NR or LHR aorta. Relaxation to S
      nitroso-N-acetyl-penicillamine and Y-27632 in denuded ionomycin-permeabilized
      rings was greater in NR than in LHR. Together these studies indicate alpha(2)-AR
      contraction depends on ROK activity more in NR than LHR aorta. Additionally,
      endogenous NO may regulate RhoA activation, whereas chronic NOS inhibition
      appears to cause RhoA desensitization.

PMID- 12234787
TI  - Quantification of interventricular asynchrony during LBBB and ventricular pacing.
AB  - The quantification of mechanical interventricular asynchrony (IVA) was
      investigated. In 12 dogs left bundle branch block (LBBB) was induced by radio
      frequency ablation. Left ventricular (LV) and right ventricular (RV) pressures
      were recorded before and after induction of LBBB and during LBBB + LV apex pacing
      at different atrioventricular (AV) delays. Four IVA measures were validated using
      computer simulations on experimentally obtained pressure signals. The most robust
      measure for IVA was the time delay between the upslope of the LV and RV pressure
      signals (DeltaT(up)), estimated by cross correlation. The induction of
      experimental LBBB decreased DeltaT(up) from -6.9 +/- 7.0 ms (RV before LV) to 
      33.9 +/- 7.6 ms (P < 0.05) in combination with a significant decrease of LV
      maximal first derivative of pressure development over time (dP/dt(max)). During
      LV apex pacing, DeltaT(up) increased with decreasing AV delay up to +20.9 +/-
      14.6 ms (P < 0.05). Interventricular resynchronization (DeltaT(up) = 0 ms)
      significantly improved LV dP/dt(max) by 15.1 +/- 5.9%. QRS duration increased
      significantly after induction of LBBB but did not change during LV apex pacing.
      In conclusion, DeltaT(up) is a reliable measure of mechanical IVA, which adds
      valuable information concerning the nature of asynchronous activation of the
      ventricles.

PMID- 12234788
TI  - Probing the link between citrate and malonyl-CoA in perfused rat hearts.
AB  - Little is known about the sources of cytosolic acetyl-CoA used for the synthesis
      of malonyl-CoA, a key regulator of fatty acid oxidation in the heart. We tested
      the hypothesis that citrate provides acetyl-CoA for malonyl-CoA synthesis after
      its mitochondrial efflux and cleavage by cytosolic ATP-citrate lyase. We expanded
      on a previous study where we characterized citrate release from perfused rat
      hearts (Vincent G, Comte B, Poirier M, and Des Rosiers C. Citrate release by
      perfused rat hearts: a window on mitochondrial cataplerosis. Am J Physiol
      Endocrinol Metab 278: E846-E856, 2000). In the present study, we show that
      citrate release rates, ranging from 6 to 22 nmol/min, can support a net increase
      in malonyl-CoA concentrations induced by changes in substrate supply, at most 0.7
      nmol/min. In experiments with [U-(13)C](lactate + pyruvate) and [1-(13)C]oleate,
      we show that the acetyl moiety of malonyl-CoA is derived from both pyruvate and
      long-chain fatty acids. This (13)C-labeling of malonyl-CoA occurred without any
      changes in its concentration. Hydroxycitrate, an inhibitor of ATP-citrate lyase,
      prevents increases in malonyl-CoA concentrations and decreases its labeling from
      [U-(13)C](lactate + pyruvate). Our data support at least a partial role of
      citrate in the transfer from the mitochondria to cytosol of acetyl units for
      malonyl-CoA synthesis. In addition, they provide a dynamic picture of malonyl-CoA
      metabolism: even when the malonyl-CoA concentration remains constant, there
      appears to be a constant need to supply acetyl-CoA from various carbon sources,
      both carbohydrates and lipids, for malonyl-CoA synthesis.

PMID- 12234789
TI  - Role of ANG II in coronary capillary angiogenesis at the insulin-resistant stage
      of a NIDDM rat model.
AB  - With the use of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of human
      non-insulin-dependent diabetes mellitus (NIDDM), we assessed whether ANG II is
      involved in coronary capillary angiogenesis at the insulin-resistant stage of
      NIDDM (20 wk of age). In OLETF rats, ANG II labeling and angiotensin type 1
      (AT(1)) receptor expression in coronary vessels were increased more than in
      nondiabetic controls. A marked increase in vascular expression of vascular
      endothelial growth factor (VEGF) at both mRNA and protein levels was found in
      OLETF rats. The increased expression level of VEGF was associated with
      accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) activated by
      increased advanced glycation end products (AGEs). Morphometric analysis showed a
      significantly increased total coronary capillary density, which was a result of
      arterialization of the venular capillary portion in OLETF rats. Treatment of
      OLETF rats with candesartan, an AT(1) receptor blocker, inhibited vascular
      expressions of VEGF, HIF-1alpha, and AGEs, and ameliorated the morphometric
      changes. These results suggest a key role of ANG II in the pathogenesis of the
      coronary capillary remodeling in this NIDDM model.

PMID- 12234790
TI  - Defective intracellular Ca(2+) signaling contributes to cardiomyopathy in Type 1
      diabetic rats.
AB  - The goal of the study was to determine whether defects in intracellular Ca(2+)
      signaling contribute to cardiomyopathy in streptozotocin (STZ)-induced diabetic
      rats. Depression in cardiac systolic and diastolic function was traced from live
      diabetic rats to isolated individual myocytes. The depression in contraction and
      relaxation in myocytes was found in parallel with depression in the rise and
      decline of intracellular free Ca(2+) concentration ([Ca(2+)](i)). The
      sarcoplasmic reticulum (SR) Ca(2+) store and rates of Ca(2+) release and
      resequestration into SR were depressed in diabetic rat myocytes. The rate of
      Ca(2+) efflux via sarcolemmal Na(+)/Ca(2+) exchanger was also depressed. However,
      there was no change in the voltage-dependent L-type Ca(2+) channel current that
      triggers Ca(2+) release from the SR. The depression in SR function was associated
      with decreased SR Ca(2+)-ATPase and ryanodine receptor proteins and increased
      total and nonphosphorylated phospholamban proteins. The depression of
      Na(+)/Ca(2+) exchanger activity was associated with a decrease in its protein
      level. Thus it is concluded that defects in intracellular Ca(2+) signaling caused
      by alteration of expression and function of the proteins that regulate
      [Ca(2+)](i) contribute to cardiomyopathy in STZ-induced diabetic rats. The
      increase in phospholamban, decrease in Na(+)/Ca(2+) exchanger, and unchanged L
      type Ca(2+) channel activity in this model of diabetic cardiomyopathy are
      distinct from other types of cardiomyopathy.

PMID- 12234791
TI  - Arterial intima-media thickness: site-specific associations with HRT and habitual
      exercise.
AB  - We determined the site-specific relations of hormone replacement therapy (HRT)
      and habitual exercise status with intima-media thickness (IMT) in both elastic
      (carotid) and muscular (femoral) arteries in 77 healthy postmenopausal women: 43
      women were sedentary (20 no-HRT and 23 HRT users) and 34 women were endurance
      trained (14 no-HRT and 20 HRT users). Femoral IMT was not different among the
      sedentary HRT and endurance-trained no-HRT and HRT groups, but was lower (P <
      0.005) in these three groups than in the sedentary no-HRT women. There were no
      significant group differences in carotid IMT. However, in older women (> or =65
      yrs) carotid IMT was smaller (P < 0.05) in HRT compared with no-HRT women. We
      conclude that both endurance training and HRT status are independently associated
      with a smaller IMT and these effects are evident primarily in muscular arteries.
      These results suggest that HRT and habitual exercise may protect postmenopausal
      women against cardiovascular disease through influences on IMT. The site-specific
      relations may be due to a greater number of smooth muscle cells and plasticity of
      muscular arteries compared with elastic arteries and/or differences in
      heterogeneous influences such as metabolic requirements and hydrostatic
      pressures.

PMID- 12234792
TI  - Peroxynitrite triggers a delayed resistance of coronary endothelial cells against
      ischemia-reperfusion injury.
AB  - Experiments were designed to test whether nitric oxide (NO) and peroxynitrite
      trigger delayed coronary endothelial protection induced by preconditioning (PC)
      in rats. Prolonged ischemia reperfusion markedly reduced the response of isolated
      coronary arteries to acetylcholine, and this was prevented by PC performed 24 h
      earlier. The NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L
      NAME) administered during PC abolished its delayed endothelial protective effect,
      whereas the inducible NOS inhibitor N-(3(aminomethyl)benzyl)acetaminide had no
      effect. Delayed endothelial PC was also abolished by the peroxynitrite scavengers
      selenomethionine or uric acid given during PC. In parallel, the NO/peroxynitrite
      donor S-morpholinosydnonimine and authentic peroxynitrite, administered 24 h
      before prolonged ischemia-reperfusion mimicked endothelial PC, whereas the NO
      donor S-nitroso-N-acetylpencillamine had no effect. This suggests that
      peroxynitrite is an essential trigger of the delayed coronary endothelial
      protection induced by PC in rat hearts.

PMID- 12234793
TI  - Angiotensin II contributes to arterial compliance in congestive heart failure.
AB  - Arterial compliance is determined by structural factors, such as collagen and
      elastin, and functional factors, such as vasoactive neurohormones. To determine
      whether angiotensin II contributes to decreased arterial compliance in patients
      with heart failure, this study tested the hypothesis that administration of an
      angiotensin-converting enzyme inhibitor improves arterial compliance. Arterial
      compliance and stiffness were determined by measuring carotid artery diameter,
      using high-resolution duplex ultrasonography, and blood pressure in 23 patients
      with heart failure secondary to idiopathic dilated cardiomyopathy. Measurements
      were made before and after intravenous administration of enalaprilat (1 mg) or
      vehicle. Arterial compliance was inversely related to both baseline plasma
      angiotensin II (r = -0.52; P = 0.015) and angiotensin-converting enzyme
      concentrations (r = -0.45; P = 0.041). During isobaric conditions, enalaprilat
      increased carotid artery compliance from 3.0 +/- 0.4 to 5.0 +/- 0.4 x 10(-10) N(
      1). m(4) (P = 0.001) and decreased the carotid artery stiffness index from 17.5
      +/- 1.8 to 10.1 +/- 0.6 units (P = 0.001), whereas the vehicle had no effect.
      Thus angiotensin II is associated with reduced carotid arterial compliance in
      patients with congestive heart failure, and angiotensin-converting enzyme
      inhibition improves arterial elastic properties. This favorable effect on the
      pulsatile component of afterload may contribute to the improvement in left
      ventricular performance that occurs in patients with heart failure treated with
      angiotensin-converting enzyme inhibitors.

PMID- 12234794
TI  - Differential involvement of MMP-2 and VEGF during muscle stretch- versus shear
      stress-induced angiogenesis.
AB  - Capillary growth in skeletal muscle occurs via the dissimilar processes of
      abluminal sprouting or longitudinal splitting, which can be initiated by muscle
      stretch and elevated shear stress, respectively. The distinct morphological
      hallmarks of these types of capillary growth suggest that discrete sets of
      angiogenic mediators play a role in each situation. Because proteolysis and
      proliferation are two key steps associated with capillary growth, we tested
      whether differences in the regulation of matrix metalloproteinases (MMPs) or VEGF
      may be associated with the two types of capillary growth. We found significant
      increases in MMP-2 total protein and percent activation, and membrane type-1 MMP
      mRNA levels, compared with controls after muscle stretch but not after shear
      stress stimulation. In contrast, VEGF protein and endothelial cell proliferation
      increased after either angiogenic stimulus. We observed that MMP-2 regulation
      occurs independent of VEGF signaling, because VEGF did not induce MMP-2
      production or activation in isolated endothelial cells. Our data suggest that the
      involvement of MMPs in capillary growth is dependent on the nature of the
      angiogenic stimulus.

PMID- 12234795
TI  - Left ventricular targeting of reporter gene expression in vivo by human BNP
      promoter in an adenoviral vector.
AB  - To selectively introduce genes into the mouse myocardium, we used a recombinant
      adenovirus encoding a transgene composed of a cardiac-specific promoter [the
      proximal human brain natriuretic peptide (hBNP) promoter] coupled to a luciferase
      reporter gene (Ad.hBNPLuc). Activity in vitro and in vivo was compared with
      Ad.CMVLuc, which contained the cytomegalovirus (CMV) enhancer/promoter. We tested
      cell-specific and inducible regulation of Ad.hBNPLuc in vitro. Expression was
      higher in neonatal cardiac myocytes than in a fibroblast cell line and was
      induced by interleukin-1beta, phenylephrine, and isoproterenol in myocytes. For
      in vivo experiments, Ad.hBNPLuc, Ad.CMVLuc, or vehicle was injected into the left
      ventricular (LV) free wall of the mouse heart. In Ad.hBNPLuc-injected mice,
      luciferase activity was only detected in the heart. In contrast, Ad.CMVLuc
      injected mice had detectable luciferase activity in all tissues examined. Our
      studies indicate that 1) the cardiac-specific hBNP promoter and direct cardiac
      injection limit expression of the transgene to the LV free wall; and 2) transgene
      expression in vitro is inducible and cardiac myocyte specific. Thus the use of
      the proximal hBNP promoter in recombinant adenoviral vectors may allow cardiac
      specific and inducible expression of therapeutic genes in vivo and prevent some
      of the side effects of systemic adenovirus administration.

PMID- 12234796
TI  - Molecular mechanics of mouse cardiac myosin isoforms.
AB  - Two myosin isoforms are expressed in myocardium, alphaalpha-homodimers (V(1)) and
      betabeta-homodimers (V(3)). V(1) exhibits higher velocities and myofibrillar
      ATPase activities compared with V(3). We also observed this for cardiac myosin
      from normal (V(1)) and propylthiouracil-treated (V(3)) mice. Actin velocity in a
      motility assay (V(actin)) over V(1) myosin was twice that of V(3) as was the
      myofibrillar ATPase. Myosin's average force (F(avg)) was similar for V(1) and
      V(3). Comparing V(actin) and F(avg) across species for both V(1) and V(3), our
      laboratory showed previously (VanBuren P, Harris DE, Alpert NR, and Warshaw DM.
      Circ Res 77: 439-444, 1995) that mouse V(1) has greater V(actin) and F(avg)
      compared with rabbit V(1). Mouse V(3) V(actin) was twice that of rabbit V(actin).
      To understand myosin's molecular structure and function, we compared alpha- and
      beta-cardiac myosin sequences from rodents and rabbits. The rabbit alpha- and
      beta-cardiac myosin differed by eight and four amino acids, respectively,
      compared with rodents. These residues are localized to both the motor domain and
      the rod. These differences in sequence and mechanical performance may be an
      evolutionary attempt to match a myosin's mechanical behavior to the heart's power
      requirements.

PMID- 12234797
TI  - Monocyte chemotactic protein-1 directly induces human vascular smooth muscle
      proliferation.
AB  - Although monocyte chemotactic protein-1 (MCP-1) is best known for its ability to
      recruit mononuclear cells, few studies have examined the effects of this
      chemokine on other events in the vascular response to injury. The purpose of the
      present study was to determine the influence of MCP-1 on human vascular smooth
      muscle (VSMC) proliferation. MCP-1 induced concentration-dependent VSMC
      proliferation as measured by bromodeoxyuridine (BrdU) uptake. Direct cell
      counting demonstrated a twofold increase in VSMC after stimulation with MCP-1.
      This mitogenic effect was similar to that observed with the prototypical
      atherogenic cytokine platelet-derived growth factor. Immunohistochemistry and
      Western blot analysis revealed that MCP-1 increased both proliferating nuclear
      cell antigen and cyclin A expression. Whereas MCP-1 did not promote nuclear
      factor-kappaB activation, MCP-1-induced VSMC proliferation appeared to be
      dependent on phosphotidylinositol 3-kinase activation. In conclusion, MCP-1
      directly induces VSMC growth, which is associated with activation of cell cycle
      proteins and intracellular proliferative signals. Within the inflammatory
      paradigm of vascular remodeling, these data suggest that MCP-1 is more than
      simply a chemokine but also a potent mitogen for VSMC proliferation.

PMID- 12234798
TI  - Influence of hemodynamic conditions on fractional flow reserve: parametric
      analysis of underlying model.
AB  - Pressure-based fractional flow reserve (FFR) is used clinically to evaluate the
      functional severity of a coronary stenosis, by predicting relative maximal
      coronary flow (Q(s)/Q(n)). It is considered to be independent of hemodynamic
      conditions, which seems unlikely because stenosis resistance is flow dependent.
      Using a resistive model of an epicardial stenosis (0-80% diameter reduction) in
      series with the coronary microcirculation at maximal vasodilation, we evaluated
      FFR for changes in coronary microvascular resistance (R(cor) = 0.2-0.6 mmHg. ml(
      1). min), aortic pressure (P(a) = 70-130 mmHg), and coronary outflow pressure
      (P(b) = 0-15 mmHg). For a given stenosis, FFR increased with decreasing P(a) or
      increasing R(cor). The sensitivity of FFR to these hemodynamic changes was
      highest for stenoses of intermediate severity. For P(b) > 0, FFR progressively
      exceeded Q(s)/Q(n) with increasing stenosis severity unless P(b) was included in
      the calculation of FFR. Although the P(b)-corrected FFR equaled Q(s)/Q(n) for a
      given stenosis, both parameters remained equally dependent on hemodynamic
      conditions, through their direct relationship to both stenosis and coronary
      resistance.

PMID- 12234799
TI  - Alpha(1)-AR-induced positive inotropic response in heart is dependent on myosin
      light chain phosphorylation.
AB  - The possible involvement of different kinases in the alpha(1)-adrenoreceptor (AR)
      mediated positive inotropic effect (PIE) was investigated in rat papillary muscle
      and compared with beta-AR-, endothelin receptor- and phorbol ester-induced
      changes in contractility. The alpha(1)-AR-induced PIE was not reduced by the
      inhibitors of protein kinase C (PKC), MAPK (ERK and p38), phosphatidyl inositol 3
      kinase, or calmodulin kinase II. However, PKC inhibition attenuated the effect of
      phorbol 12-myristate 13-acetate (PMA) on contractility. alpha(1)-AR-induced PIE
      was reduced by approximately 90% during inhibition of myosin light chain kinase
      (MLCK) by 1-(5-chloronaphthalene-1-sulfonyl)1H-hexahydro-1,4-diazepine (ML-9).
      Endothelin-induced PIE was also reduced by ML-9, but ML-9 had no effect on beta
      AR-induced PIE. The Rho kinase inhibitor Y-27632 also reduced the alpha(1)-AR
      induced PIE. The alpha(1)-AR-induced PIE in muscle strips from explanted failing
      human hearts was also sensitive to MLCK inhibition. alpha(1)-AR induced a modest
      increase in (32)P incorporation into myosin light chain in isolated rat
      cardiomyocytes. This effect was eliminated by ML-9. The PIE of alpha(1)-AR
      stimulation seems to be dependent on MLCK phosphorylation.

PMID- 12234800
TI  - Urocortin protects the heart from reperfusion injury via upregulation of p42/p44
      MAPK signaling pathway.
AB  - Reperfusion of ischemic myocardium is essential for tissue salvage but
      paradoxically contributes to cell death. We hypothesized that activation of
      potential survival pathways such as p42/p44 MAPK may prevent lethal reperfusion
      injury. Urocortin is a peptide factor that affects the p42/p44 MAPK signaling
      pathway. Both isolated and in vivo rat heart models were used to examine the
      potential for urocortin to prevent reperfusion injury. Isolated rat hearts
      underwent 35-min regional ischemia and 2-h reperfusion, with urocortin perfused
      for 20 min from the onset of reperfusion. In the in vivo study, urocortin was
      administered as an intravenous bolus 3 min before reperfusion with a protocol of
      25-min regional ischemia and 2-h reperfusion. Blockade of the p42/p44 MAPK
      pathway with the inhibitor PD-98059 was used in both models. Urocortin attenuated
      lethal reperfusion-induced injury both in vitro and in vivo via a p42/p44 MAPK
      dependent mechanism. Furthermore, Western blot analysis demonstrated the ability
      of urocortin to directly upregulate this signaling pathway. In conclusion, we
      believe that the p42/p44 MAPK-dependent signaling pathway represents an important
      survival mechanism against reperfusion injury.

PMID- 12234801
TI  - Mechanosensitive release of parathyroid hormone-related peptide from coronary
      endothelial cells.
AB  - 10.1152/ajpheart.00925. 2001.-Parathyroid hormone-related peptide (PTHrP) is
      expressed throughout the cardiovascular system and is able to dilate vessels.
      This study investigated whether mechanical forces generated by changes in
      regional perfusion influence PTHrP release from the coronary vascular bed.
      Experiments were performed in vitro on saline-perfused rat hearts or isolated
      coronary endothelial cells exposed to cyclic strain and in vivo in anesthetized
      pigs. In vitro, PTHrP release from saline-perfused rat hearts was strongly
      correlated with coronary flow (r = 0.84). Increasing coronary flow from 5 to 10
      ml/min increased PTHrP release from 442 +/- 42 to 1,563 +/- 167 pg/min.
      Increasing the viscosity of the perfusate did not change basal PTHrP release.
      Increasing flow without a concomitant increase in pressure did not lead to an
      increase in release rate, but reduction in pressure under flow-constant
      conditions reduced PTHrP release rate. Cyclic strain induced a strain-dependent
      release of PTHrP from endothelial cells that was inhibited by the addition of a
      calcium-chelating agent. In vivo, there was a net release of PTHrP in the
      coronary circulation and decreases in coronary flow and pressure decreased the
      PTHrP release rate. Bradykinin in the presence of constant pressure increased
      PTHrP release, probably by increasing the intracellular calcium concentration in
      coronary endothelial cells. In summary, mechanical forces evoked by blood flow
      can trigger a constant PTHrP release.

PMID- 12234802
TI  - Hu protein R-mediated posttranscriptional regulation of VEGF expression in rat
      gastrocnemius muscle.
AB  - Hypoxic exercise increases VEGF expression and the formation of new capillaries.
      In addition to hypoxia-inducible factor regulation at the transcriptional level,
      VEGF message stabilization is also a key regulatory step for VEGF expression. In
      vitro experiments have identified Hu protein R (HuR) as a potential
      posttranscriptional regulator of VEGF gene expression. Here, we report that in
      rat skeletal muscle (gastrocnemius muscle), 1) HuR binds to a known regulatory
      sequence located in the VEGF mRNA 3'-untranslated region (1,631-1,678 bp); 2) HuR
      specifically binds to the A/U-rich element AUUUUA (1,665-1,670 bp) and an
      additional A/U-rich region containing the consensus sequence UUUUUUA (1,658-1,664
      bp); 3) binding of HuR to VEGF mRNA is seen already 5 min after acute ischemia,
      remaining elevated throughout a 60-min ischemic period; 4) a second inducible HuR
      VEGF mRNA binding factor is evident 30 and 60 min postischemia; and 5) VEGF mRNA
      and protein levels are increased 20 and 30 min, respectively, after acute
      ischemia. These findings suggest that acute ischemia induces a rapid binding of
      HuR to the VEGF mRNA 3'-untranslated region. In skeletal muscle, this specific
      protein-RNA interaction may be an important posttranscriptional regulatory
      mechanism for increasing VEGF expression in response to hypoxia or acute
      ischemia.

PMID- 12234803
TI  - Reverse flux through cardiac NADP(+)-isocitrate dehydrogenase under normoxia and
      ischemia.
AB  - Little is known about the role of mitochondrial NADP(+)-isocitrate dehydrogenase
      (NADP(+)-ICDH) in the heart, where this enzyme shows its highest expression and
      activity. We tested the hypothesis that in the heart, NADP(+)-ICDH operates in
      the reverse direction of the citric acid cycle (CAC) and thereby may contribute
      to the fine regulation of CAC activity (Sazanov and Jackson, FEBS Lett 344: 109
      116, 1994). We documented a reverse flux through this enzyme in rat hearts
      perfused with the medium-chain fatty acid octanoate using [U-(13)C(5)]glutamate
      and mass isotopomer analysis of tissue citrate (Comte et al., J Biol Chem 272:
      26117-26124, 1997). In this study, we assessed the significance of our previous
      finding by perfusing hearts with long-chain fatty acids and tested the effects of
      changes in O(2) supply. We showed that under all of these conditions citrate was
      enriched in an isotopomer containing five (13)C atoms. This isotopomer can only
      be explained by substrate flux through reversal of the NADP(+)-ICDH reaction,
      which is evaluated at 3-7% of flux through citrate synthase. Small variations in
      reversal fluxes induced by low-flow ischemia that mimicked hibernation occurred
      despite major changes in contractile function and O(2) consumption of the heart
      as well as citrate and succinate release rates and tissue levels. Our data show a
      reverse flux through NADP(+)-ICDH and support its hypothesized role in the fine
      regulation of CAC activity in the normoxic and O(2)-deprived heart.

PMID- 12234804
TI  - Coronary perfusion and muscle lengthening increase cardiac contraction: different
      stretch-triggered mechanisms.
AB  - An increase in coronary perfusion, transversal stretch of the myocardium,
      increases developed force (F(dev)) (Gregg effect) through activation of stretch
      activated ion channels (SACs). Lengthening of the muscle, longitudinal stretch of
      the myocardium, causes an immediate increase in F(dev) followed by a slow F(dev)
      increase (Anrep effect). In isometrically contracting perfused papillary muscles
      of Wistar rats, we investigated whether both effects were based on similar
      stretch-induced mechanisms by measuring F(dev) and intracellular Ca(2+)
      concentration ([Ca(2+)](i)) after a muscle length increase from 85% to 95% L(max)
      (length at which maximal isometric force develops) at low and high coronary
      perfusion before and after inhibition of SACs with gadolinium (10 micromol/l
      Gd(3+)). The increase of F(dev) and peak [Ca(2+)](i) by the Gregg effect was of
      similar magnitude as the Anrep effect (from 3.5 +/- 0.8 to 3.9 +/- 1.2 mN/mm(2)
      and from 3.0 +/- 0.7% to 3.8 +/- 0.9% normalized [Ca(2+)](i), means +/- SE). SAC
      blockade completely blunted the increase of F(dev) and peak [Ca(2+)](i) by the
      Gregg effect; however, it did not affect the Anrep effect. The slow force
      response, but not the calcium response, was augmented by an increase in coronary
      perfusion. Therefore, increased coronary perfusion, transversal stretch of the
      myocardium, and muscle lengthening, longitudinal stretch of the myocardium,
      increase myocardial contraction in the rat through different stretch-triggered
      mechanisms.

PMID- 12234805
TI  - Endothelin-induced modulation of neuropeptide Y and norepinephrine release from
      the rat mesenteric bed.
AB  - The effect of three endothelin (ET) agonists [ET-1, ET-3, and sarafotoxin
      (STX6C)] on the nerve stimulation-induced release of norepinephrine (NE) and
      neuropeptide Y-immunoreactive compounds (NPY-ir) from the perfused mesenteric
      arterial bed of the rat as well as the effect on perfusion pressure were
      examined. ET-1, ET-3, and STX6C all produced a significant, concentration
      dependent decrease in the evoked release of NPY-ir but had no effect on the
      release of NE. In contrast, all three ETs potentiated the nerve stimulation
      induced increase in perfusion pressure. The inhibition of nerve stimulation
      induced NPY-ir release by ET-1 was significantly blocked by the ET(A)/ET(B)
      antagonist PD-142893 and the ET(B) antagonist RES-701-1 but not by the ET(A)
      antagonist BQ-123. The potentiation of the nerve stimulation-induced increase in
      perfusion pressure by ET-1 was significantly blocked by PD-142893 and BQ-123 and
      attenuated by RES-701-1. Prior exposure of the preparation to indomethacin or
      meclofenamate failed to alter the attenuation of the evoked release of NPY-ir or
      the potentiation of the increase in perfusion pressure produced by ET-1 or ET-3.
      These results are consistent with the idea that sympathetic cotransmitters can be
      preferentially modulated by paracrine mediators at the vascular neuroeffector
      junction.

PMID- 12234806
TI  - Blood-brain barrier tight junctions are altered during a 72-h exposure to lambda
      carrageenan-induced inflammatory pain.
AB  - In this study, we examined the effect of lambda-carrageenan-induced inflammatory
      pain on the functional and structural properties of the rat blood-brain barrier
      (BBB) over a 72-h time period. Systemic inflammation was induced by an
      intraplantar injection of 3% lambda-carrageenan into the right hind paw of female
      Sprague-Dawley rats. In situ brain perfusion and Western blot analyses were
      performed at 1, 3, 6, 12, 24, 48, and 72 h. In situ brain perfusion showed lambda
      carrageenan significantly increased brain uptake of [(14)C]sucrose at 1, 3, 6,
      and 48 h (139 +/- 9%, 166 +/- 19%, 138 +/- 13%, and 146 +/- 7% compared with
      control, respectively). Capillary depletion analysis insured the increased brain
      uptake was due to increased BBB permeability and not vascular trapping. Western
      blot analyses for zonula occludens-1 (ZO-1) and occludin were performed on
      isolated cerebral microvessels. ZO-1 expression was significantly increased at 1,
      3, and 6 h and returned to control expression levels by 12 h. Total occludin
      expression was significantly reduced at 1, 3, 6, 12, and 48 h. This investigation
      demonstrated that lambda-carrageenan-induced inflammatory pain elicits a biphasic
      increase in BBB permeability with the first phase occurring from 1-6 h and the
      second phase occuring at 48 h. Furthermore, changes in BBB function are
      correlated with altered tight junctional protein expression of occludin and ZO-1.
      Changes in the structure of tight junctions may have important clinical
      ramifications concerning central nervous system homeostasis and therapeutic drug
      delivery.

PMID- 12234807
TI  - Cardioprotection by multiple preconditioning cycles does not require
      mitochondrial K(ATP) channels in pigs.
AB  - To test whether cardioprotection induced by ischemic preconditioning depends on
      the opening of mitochondrial ATP-sensitive K(+) (K(ATP)) channels, the effect of
      channel blockade was studied in barbital-anesthetized open-chest pigs subjected
      to 30 min of complete occlusion of the left anterior descending coronary artery
      and 3 h of reflow. Preconditioning was elicited by two cycles of 5-min occlusion
      plus 10-min reperfusion before the 30-min occlusion period. 5-Hydroxydecanoate (5
      mg/kg iv) was injected 15 min before preconditioning or pharmacological
      preconditioning induced by diazoxide (3.5 mg/kg, 1 ml/min iv). Infarct size
      (percentage of the area at risk) after 30 min of ischemia was 35.1 +/- 9.9% (n =
      7). Preconditioning markedly limited myocardial infarct size (2.7 +/- 1.6%, n =
      7), and 5-hydroxydecanoate did not abolish protection (2.4 +/- 0.9%, n = 8).
      Diazoxide infusion also significantly limited infarct size (14.6 +/- 7.4%, n =
      7), and 5-hydroxydecanoate blocked this effect (30.8 +/- 8.0%, n = 7). Thus the
      opening of mitochondrial K(ATP) channels is cardioprotective in pigs, but these
      data do not support the hypothesis that opening of mitochondrial K(ATP) channels
      is required for the endogenous protection afforded by preconditioning.

PMID- 12234808
TI  - ATP-sensitive K(+) channel activation by nitric oxide and protein kinase G in
      rabbit ventricular myocytes.
AB  - The present investigation tested the hypothesis that nitric oxide (NO)
      potentiates ATP-sensitive K(+) (K(ATP)) channels by protein kinase G (PKG)
      dependent phosphorylation in rabbit ventricular myocytes with the use of patch
      clamp techniques. Sodium nitroprusside (SNP; 1 mM) potentiated K(ATP) channel
      activity in cell-attached patches but failed to enhance the channel activity in
      either inside-out or outside-out patches. The 8-(4-chlorophenylthio)-cGMP Rp
      isomer (Rp-CPT-cGMP, 100 microM) suppressed the potentiating effect of SNP. 8-(4
      Chlorophenylthio)-cGMP (8-pCPT-cGMP, 100 microM) increased K(ATP) channel
      activity in cell-attached patches. PKG (5 U/microl) added together with ATP and
      cGMP (100 microM each) directly to the intracellular surface increased the
      channel activity. Activation of K(ATP) channels was abolished by the replacement
      of ATP with ATPgammaS. Rp-pCPT-cGMP (100 microM) inhibited the effect of PKG. The
      heat-inactivated PKG had little effect on the K(ATP) channels. Protein
      phosphatase 2A (PP2A, 1 U/ml) reversed the PKG-mediated K(ATP) channel
      activation. With the use of 5 nM okadaic acid (a PP2A inhibitor), PP2A had no
      effect on the channel activity. These results suggest that the NO-cGMP-PKG
      pathway contributes to phosphorylation of K(ATP) channels in rabbit ventricular
      myocytes.

PMID- 12234809
TI  - Hypertension induced by blockade of ET(B) receptors in conscious nonhuman
      primates: role of ET(A) receptors.
AB  - The role of endothelin-B (ET(B)) receptors in circulatory homeostasis is
      ambiguous, reflecting vasodilator and constrictor effects ascribed to the
      receptor and diuretic and natriuretic responses that could oppose the
      hypertensive effects of ET excess. With the use of conscious, telemetry
      instrumented cynomolgus monkeys, we characterized the hypertension produced by
      ET(B) blockade and the role of ET(A) receptors in mediating this response. Mean
      arterial pressure (MAP) and heart rate (HR) were measured 24 h/day for 24 days
      under control conditions and during administration of the ET(B)-selective
      antagonist A-192621 (0.1, 1.0, and 10 mg/kg bid, 4 days/dose) followed by
      coadministration of the ET(A) antagonist atrasentan (5 mg/kg bid) + A-192621 (10
      mg/kg bid) for another 4 days. High-dose ET(B) blockade increased MAP from 79 +/-
      3 (control) to 87 +/- 3 and 89 +/- 3 mmHg on the first and fourth day,
      respectively; HR was unchanged, and plasma ET-1 concentration increased from 2.1
      +/- 0.3 pg/ml (control) to 7.24 +/- 0.99 and 11.03 +/- 2.37 pg/ml. Atrasentan + A
      192621 (10 mg/kg) decreased MAP from hypertensive levels (89 +/- 3) to 75 +/- 2
      and 71 +/- 4 mmHg on the first and fourth day, respectively; plasma ET-1 and HR
      increased to 26.64 +/- 3.72 and 28.65 +/- 2.89 pg/ml and 113 +/- 5 (control) to
      132 +/- 5 and 133 +/- 7 beats/min. Thus systemic ET(B) blockade produces a
      sustained hypertension in conscious nonhuman primates, which is mediated by ET(A)
      receptors. These data suggest an importance clearance function for ET(B)
      receptors, one that influences arterial pressure homeostasis indirectly by
      reducing plasma ET-1 levels and minimizing ET(A) activation.

PMID- 12234810
TI  - Overexpression of A(3) adenosine receptors decreases heart rate, preserves
      energetics, and protects ischemic hearts.
AB  - To determine whether A(3) adenosine receptor (A(3)AR) signaling modulates
      myocardial function, energetics, and cardioprotection, hearts from wild-type and
      A(3)AR-overexpressor mice were subjected to 20-min ischemia and 40-min
      reperfusion while (31)P NMR spectra were acquired. Basal heart rate and left
      ventricular developed pressure (LVDP) were lower in A(3)AR-overexpressor hearts
      than wild-type hearts. Ischemic ATP depletion was delayed and postischemic
      recoveries of contractile function, ATP, and phosphocreatine were greater in
      A(3)AR-hearts. To determine the role of depressed heart rate and to confirm
      A(3)AR-specific signaling, hearts were paced at 480 beats/min with or without 60
      nmol/l MRS-1220 (A(3)AR-specific inhibitor) and then subjected to ischemia
      reperfusion. LVDP was similar in paced A(3)AR-overexpressor and paced wild-type
      hearts. Differences in ischemic ATP depletion and postischemic contractile and
      energetic dysfunction remained in paced A(3)AR-overexpressor hearts versus paced
      wild-type hearts but were abolished by MRS-1220. In summary, A(3)AR
      overexpression decreased basal heart rate and contractility, preserved ischemic
      ATP, and decreased postischemic dysfunction. Pacing abolished the decreased
      contractility but not the ATP preservation or cardioprotection. Therefore, A(3)AR
      overexpression results in cardioprotection via a specific A(3)AR effect, possibly
      involving preservation of ATP during ischemia.

PMID- 12234811
TI  - Superoxide contributes to vascular dysfunction in mice that express human renin
      and angiotensinogen.
AB  - This study examined vascular function and the role of superoxide in mice that
      chronically express human renin (R+) and human angiotensinogen (A+). Responses of
      aortas from R+/A+ mice and from their normotensive littermates (RA- mice) were
      examined in vitro. Endothelium-dependent relaxation to acetylcholine was impaired
      in vessels from R+/A+ mice (e.g., maximal relaxation to 100 microM acetylcholine
      was 45 +/- 5% and 65 +/- 3% in R+/A+ and RA- mice, respectively; P < 0.05).
      Relaxation was also impaired to the endothelium-independent dilators authentic
      nitric oxide and nitroprusside in vessels from R+/A+ mice. Maximal vasorelaxation
      to the endothelium-independent, non-nitric oxide dilator papaverine was similar
      in R+/A+ and RA- mice. Incubation of vessels from R+/A+ mice with Tiron (1 mM), a
      superoxide scavenger, improved relaxation to acetylcholine, nitric oxide, and
      nitroprusside. In contrast, incubation with diethyldithiocarbamate (1 mM), an
      inhibitor of copper-containing SODs, reduced acetylcholine- and nitroprusside
      induced relaxation in vessels from both R+/A+ and RA- mice. Basal superoxide
      levels, measured with lucigenin-enhanced chemiluminescence (5 microM lucigenin)
      and hydroethidine-based fluorescent confocal microscopy, were higher in vessels
      from R+/A+ mice and were Tiron and polyethylene glycol-SOD sensitive. These
      results suggest that increased superoxide contributes to impaired nitric oxide
      mediated relaxation in this genetic model of chronic angiotensin II-dependent
      hypertension.

PMID- 12234812
TI  - Alpha(1)-adrenoceptor stimulation directly induces growth of vascular wall in
      vivo.
AB  - Previous studies suggesting that norepinephrine is directly trophic for the
      vascular wall have been confounded by concomitant hemodynamic disturbances.
      Herein, a microcatheter connected to an osmotic minipump was implanted adjacent
      to the rat carotid for 2-wk perivascular suffusion of agents at systemic levels
      ~1,000 times below the threshold for altering arterial pressure. Norepinephrine
      decreased lumen and adventitial areas and circumference by 10, 14, and 5%,
      respectively (all P < 0.05); a nonsubtype-specific alpha(1)-adrenoceptor (AR)
      antagonist had no effect. When begun at the time of balloon injury, 2-wk
      norepinephrine increased lumen loss by 45%, increased neointimal area by 64% and
      collagen content by 33%, and reduced vessel circumference by 5% (all P < 0.05).
      alpha(1)-AR antagonists decreased neointimal area by 33% (all P < 0.05).
      alpha(1)A-AR antagonist reduced lumen loss by 70%, neointimal area by 54%,
      circumference decline by 84%, and adventitial thickening by 87% (all P < 0.05),
      whereas alpha(1B)-, alpha(1D)-, alpha(2)- and beta-AR antagonists were without
      effect. These are the first in vivo studies demonstrating that norepinephrine is
      directly trophic for the vascular wall and augments injury-induced intimal lesion
      growth.

PMID- 12234813
TI  - Mechanisms mediating regional sympathoactivatory responses to stimulation of NTS
      A(1) adenosine receptors.
AB  - Selective activation of adenosine A(1) and A(2a) receptors in the subpostremal
      nucleus tractus solitarius (NTS) increases and decreases mean arterial pressure
      (MAP), respectively, and decreases heart rate (HR). We have previously shown that
      the decreases in MAP evoked by NTS A(2a) receptor stimulation were accompanied
      with differential sympathetic responses in renal (RSNA), lumbar (LSNA), and
      preganglionic adrenal sympathetic nerve activity (pre-ASNA). Therefore, now we
      investigated whether stimulation of NTS A(1) receptors via unilateral
      microinjection of N(6)-cyclopentyladenosine (CPA) elicits differential activation
      of the same sympathetic outputs in alpha-chloralose-urethane-anesthetized male
      Sprague-Dawley rats. CPA (0.33-330.0 pmol in 50 nl) evoked dose-dependent
      increases in MAP, variable decreases in HR, and differential increases in all
      recorded sympathetic outputs: upward arrow pre-ASNA >> upward arrow RSNA > or =
      upward arrow LSNA. Sinoaortic denervation + vagotomy abolished the MAP and LSNA
      responses, reversed the normal increases in RSNA into decreases, and
      significantly attenuated increases in pre-ASNA. NTS ionotropic glutamatergic
      receptor blockade with kynurenate sodium (4.4 nmol/100 nl) reversed the responses
      in MAP, LSNA, and RSNA and attenuated the responses in pre-ASNA. We conclude that
      afferent inputs and intact glutamatergic transmission in the NTS are necessary to
      mediate the pressor and differential sympathoactivatory responses to stimulation
      of NTS A(1) receptors.

PMID- 12234814
TI  - Role of oxidative phosphorylation and ATP release in mediating birth-related
      pulmonary vasodilation in fetal lambs.
AB  - We investigated the hypothesis that birth-related pulmonary vasodilation is
      mediated in part by an increase in oxidative phosphorylation and ATP release in
      response to oxygen exposure at birth. Studies were done in fetal lambs to
      evaluate the independent effects of oxygen, lung distension alone, or lung
      distension accompanied by oxygenation and shear stress on fetal pulmonary blood
      flow and resistance and plasma ATP levels in the pulmonary artery. The effect of
      each intervention was evaluated in lambs assigned to one of three groups: control
      or pretreatment with 2,4-dinitrophenol or antimycin-A, inhibitors of oxidative
      phosphorylation. Exposure to oxygen alone or with lung distension was associated
      with increases in plasma ATP levels and pulmonary blood flow and a decrease in
      pulmonary vascular resistance. Plasma ATP levels did not change during lung
      distension alone. 2,4-Dinitrophenol and antimycin-A attenuated the pulmonary
      vasodilator response to oxygen but did not attenuate the response to lung
      distension alone. An increase in oxidative phosphorylation and ATP release during
      oxygen exposure may contribute to birth-related pulmonary vasodilation in fetal
      lambs.

PMID- 12234815
TI  - Transmural gradients of cardiac myofiber shortening in aortic valve stenosis
      patients using MRI tagging.
AB  - Aortic valve stenosis impairs subendocardial perfusion with a risk of
      irreversible subendocardial tissue damage. A likely precursor of damage is
      subendocardial contractile dysfunction, expressed by the parameter TransDif,
      which is defined as epicardial minus endocardial myofiber shortening, normalized
      to the mean value. With the use of magnetic resonance tagging in two short-axis
      slices of the left ventricle (LV), TransDif was derived from LV torsion and
      contraction during ejection. TransDif was determined in healthy volunteers
      (control, n = 9) and in patients with aortic valve stenosis before (AVSten, n =
      9) and 3 mo after valve replacement (AVRepl, n = 7). In the control group,
      TransDif was 0.00 +/- 0.14 (mean +/- SD). In the AVSten group, TransDif increased
      to 0.96 +/- 0.62, suggesting impairment of subendocardial myofiber shortening. In
      the AVRepl group, TransDif decreased to 0.37 +/- 0.20 but was still elevated. In
      eight of nine AVSten patients, the TransDif value was elevated individually (P <
      0.001), suggesting that the noninvasively determined parameter TransDif may
      provide important information in planning of treatment of aortic valve stenosis.

PMID- 12234816
TI  - Effects of Na(+)/Ca(2+) exchanger downregulation on contractility and [Ca(2+)](i)
      transients in adult rat myocytes.
AB  - Postmyocardial infarction (MI) rat myocytes demonstrated depressed Na(+)/Ca(2+)
      exchange (NCX1) activity, altered contractility, and intracellular Ca(2+)
      concentration ([Ca(2+)](i)) transients. We investigated whether NCX1
      downregulation in normal myocytes resulted in contractility changes observed in
      MI myocytes. Myocytes infected with adenovirus expressing antisense (AS)
      oligonucleotides to NCX1 had 30% less NCX1 at 3 days and 66% less NCX1 at 6 days.
      The half-time of relaxation from caffeine-induced contracture was twice as long
      in ASNCX1 myocytes. Sarcoplasmic reticulum (SR) Ca(2+)-ATPase abundance, SR
      Ca(2+) uptake, resting membrane potential, action potential amplitude and
      duration, L-type Ca(2+) current density and cell size were not affected by ASNCX1
      treatment. At extracellular Ca(2+) concentration ([Ca(2+)](o)) of 5 mM, ASNCX1
      myocytes had significantly lower contraction and [Ca(2+)](i) transient amplitudes
      and SR Ca(2+) contents than control myocytes. At 0.6 mM [Ca(2+)](o), contraction
      and [Ca(2+)](i) transient amplitudes and SR Ca(2+) contents were significantly
      higher in ASNCX1 myocytes. At 1.8 mM [Ca(2+)](o), contraction and [Ca(2+)](i)
      transient amplitudes were not different between control and ASNCX1 myocytes. This
      pattern of contractile and [Ca(2+)](i) transient abnormalities in ASNCX1 myocytes
      mimics that observed in rat MI myocytes. We conclude that downregulation of NCX1
      in adult rat myocytes resulted in decreases in both Ca(2+) influx and efflux
      during a twitch. We suggest that depressed NCX1 activity may partly account for
      the contractile abnormalities after MI.

PMID- 12234817
TI  - Structural and functional changes in left ventricle during normotensive and
      preeclamptic pregnancy.
AB  - Increased cardiac output in pregnancy is associated with cardiac remodeling and
      possible reduction in contractility, which may worsen in preeclampsia. Left
      ventricular (LV) geometry and function were compared between nonpregnant controls
      (n = 12) and normotensive (n = 44) and preeclamptic (n = 15) pregnant women using
      echocardiography. Load-independent comparisons of LV systolic function compared
      end-systolic stress (ESS) and rate-corrected velocity of circumferential fiber
      shortening (V(CFC)). Mean arterial pressures were 101 +/- 14 mmHg in
      preeclampsia, 76 +/- 6 mmHg in normotensive pregnancy, and 78 +/- 6 mmHg in
      controls (P < 0.005 vs. preeclampsia). LV mass increased during normotensive
      pregnancy (66 +/- 13 to 76 +/- 16 g/m(2); P < 0.05; controls, 65 +/- 10 g/m(2); P
      < 0.05) and was greater in preeclampsia (90 +/- 18 g/m(2); P < 0.05). In
      normotensive pregnancy, ESS decreased (59 +/- 9 to 52 +/- 11 g/cm(2); P < 0.05;
      controls, 66 +/- 14 g/cm(2); P < 0.005). ESS was greater in preeclampsia (60 +/-
      14 g/cm(2); P < 0.05). In controls, there was an inverse relationship between ESS
      and V(CFC) (r = -0.78). The ESS-V(CFC) relationships in normotensive and
      preeclamptic pregnancy were unchanged from controls. We conclude that LV
      hypertrophy in normotensive and preeclamptic pregnancy matches changes in cardiac
      work, and LV contractility is preserved.

PMID- 12234818
TI  - Pyruvate improves redox status and decreases indicators of hepatic apoptosis
      during hemorrhagic shock in swine.
AB  - Previous studies have shown that the liver is the first organ to display signs of
      injury during hemorrhagic shock. We examined the mechanism by which pyruvate can
      prevent liver damage during hemorrhagic shock in swine anesthetized with
      halothane. Thirty minutes after the induction of a 240-min controlled arterial
      hemorrhage targeted at 40 mmHg, hypertonic sodium pyruvate (0.5 g. kg(-1). h(-1))
      was infused to achieve an arterial concentration of 5 mM. The volume and
      osmolality effects of pyruvate were matched with 10% saline (HTS) and 0.9% saline
      (NS). Although the peak hemorrhage volume increased significantly in both the
      pyruvate and HTS group, only the pyruvate treatment was effective in delaying
      cardiovascular decompensation. In addition, pyruvate effectively maintained the
      NADH/NAD redox state, as evidenced by increased microdialysate pyruvate levels
      and a significantly lower lactate-to-pyruvate ratio. Pyruvate also prevented the
      loss of intracellular antioxidants (GSH) and a reduction in the GSH-to-GSSG
      ratio. These beneficial effects on the redox environment decreased hepatic
      cellular death by apoptosis. Pyruvate significantly increased the ratio of Bcl-Xl
      (antiapoptotic molecule)/Bax (proapoptotic molecule), prevented the release of
      cytochrome c from mitochondria, and decreased the fragmentation of caspase 3 and
      poly(ADP ribose) polymerase (DNA repair enzyme). These beneficial findings
      indicate that pyruvate infused 30 min after the onset of severe hemorrhagic shock
      is effective in maintaining the redox environment, preventing the loss of the key
      antioxidant GSH, and decreasing early apoptosis indicators.

PMID- 12234819
TI  - TLR4 inactivation and rBPI(21) block burn-induced myocardial contractile
      dysfunction.
AB  - Both large burns and severe gram-negative sepsis are associated with acute
      myocardial contractile dysfunction. Because others have reported that burn injury
      may be followed by transient endotoxemia, we hypothesized that bacterial
      endotoxin induces contractile impairment after burn trauma. We tested this
      hypothesis in two rodent models. In each model, postburn myocardial contractility
      was assessed using Langendorff preparations of excised hearts. In the first
      model, mice expressing either a mutant form of or no Toll-like receptor 4 (TLR4),
      a critical element of the mammalian endotoxin receptor, were resistant to
      postburn myocardial contractile dysfunction. In the second model, starting 30 min
      or 4 h after burn injury, rats were infused with recombinant
      bactericidal/permeability-increasing protein (rBPI(21)), a protein that binds and
      neutralizes endotoxin. Hearts from rBPI(21)-treated animals were completely
      protected from postburn contractile impairment. Because burn-induced contractile
      dysfunction can be prevented either by blocking signaling through the endotoxin
      receptor or by neutralizing circulating LPS, bacterial endotoxin may contribute
      to impaired myocardial contractility after burn injury.

PMID- 12234820
TI  - Reactive oxygen species generated during myocardial ischemia enable energetic
      recovery during reperfusion.
AB  - We studied the differences between the functional and bioenergetic effects of
      antioxidants (AOX) administered before or after myocardial ischemia. Sprague
      Dawley rat hearts were perfused with a modified Krebs-Henseleit solution and
      bubbled with 95% O(2)-5% CO(2). The protocol consisted of 10 min of baseline
      perfusion, 20 min of global ischemia, and 30 min of reperfusion. An AOX, either
      1,2-dihydroxybenzene-3,5-disulfonate (Tiron), a superoxide scavenger, or N-acetyl
      L-cysteine, was infused during either baseline or reperfusion. An additional
      group received deferoxamine as a bolus before ischemia. Hearts were freeze
      clamped at baseline, at end of ischemia, and at end of reperfusion for analysis
      of high-energy phosphates. All AOX, when given before ischemia, inhibited
      recovery of ATP compared with controls. Both Tiron and deferoxamine also
      inhibited recovery of phosphocreatine. AOX given before ischemia decreased the
      efficiency of contraction during reperfusion compared with controls. All of the
      changes in energetics and efficiency brought on by preischemic AOX treatment
      could be blocked by a preconditioning stimulus. This suggests that reactive
      oxygen species, which are generated during ischemia, enhance bioenergetic
      recovery by increasing the efficiency of contraction.

PMID- 12234821
TI  - Aging impairs endothelium-dependent vasodilation in rat skeletal muscle
      arterioles.
AB  - Blood flow capacity in skeletal muscle declines with age. Reduced blood flow
      capacity may be related to decline in the maximal vasodilatory capacity of the
      resistance vasculature. This study tested the hypothesis that aging results in
      impaired vasodilatory capacity of first-order (1A) arterioles isolated from rat
      hindlimb locomotory muscle: 1A arterioles (90-220 microm) from gastrocnemius and
      soleus muscles of young (4 mo) and aged (24 mo) Fischer-144 rats were isolated,
      cannulated, and pressurized via hydrostatic reservoirs. Vasodilatory responses to
      increasing concentrations of ACh (10(-9) to 10(-4) M), adenosine (ADO, 10(-10) to
      10(-4) M), and sodium nitroprusside (SNP, 10(-10) to 10(-4) M) were evaluated at
      a constant intraluminal pressure of 60 cmH(2)O in the absence of flow. Flow
      induced vasodilation was also evaluated in the absence of pressure changes.
      Responses to ADO and SNP were not altered by age. Endothelium-dependent
      vasodilation induced by flow was significantly reduced in arterioles from both
      gastrocnemius and soleus muscles. In contrast, endothelium-dependent vasodilation
      to ACh was reduced only in soleus muscle arterioles. These results indicate that
      aging impairs vasodilatory responses mediated through the endothelium of
      resistance arterioles from locomotory muscle, whereas smooth muscle vasodilatory
      responses remain intact with aging. Additionally, ACh-induced vasodilation was
      altered by age only in soleus muscle arterioles, suggesting that the mechanism of
      age-related endothelial impairment differs in arterioles from soleus and
      gastrocnemius muscles.

PMID- 12234822
TI  - Tyrosine kinases regulate intracellular calcium during alpha(2)-adrenergic
      contraction in rat aorta.
AB  - We have demonstrated enhanced contractile sensitivity to the alpha(2)
      adrenoreceptor (alpha(2)-AR) agonist UK-14304 in arteries from rats made
      hypertensive with chronic nitric oxide synthase (NOS) inhibition (LHR) compared
      with arteries from normotensive rats (NR); additionally, this contraction
      requires Ca(2+) entry. We hypothesized that tyrosine kinases augment alpha(2)-AR
      contraction in LHR arteries by increasing Ca(2+). The tyrosine kinase inhibitor
      tyrphostin 23 significantly attenuated UK-14304 contraction of denuded thoracic
      aortic rings from NR and LHR. However, tyrphostin 23 did not alter UK-14304
      contraction in ionomycin-permeabilized aorta, which indicates that tyrosine
      kinases regulate intracellular Ca(2+) concentration. The Src family inhibitor PP1
      and the epidermal growth factor receptor kinase inhibitor AG-1478 did not alter
      alpha(2)-AR contraction, whereas the mitogen-activated protein kinase
      extracellular signal-regulated kinase kinase inhibitor PD-98059 attenuated the
      contraction. Contraction to CaCl(2) in ionomycin-permeabilized LHR rings was
      greater than in NR rings. UK-14304 augmented CaCl(2) contraction in ionomycin
      permeabilized rings from both groups but to a greater extent in LHR aorta.
      Together, these data suggest that alpha(2)-AR stimulates contraction via two
      pathways. One, which is enhanced with NOS inhibition hypertension, activates
      Ca(2+) sensitivity and is independent of tyrosine kinases. The other is tyrosine
      kinase dependent and regulates intracellular Ca(2+) concentration.

PMID- 12234823
TI  - Preload-adjusted maximal power of right ventricle: contribution of end-systolic P
      V relation intercept.
AB  - To assess whether preload-adjusted maximal power (PAMP), which is calculated as
      W(max)/V (where W(max) is maximal power and V(ed) is end-diastolic volume with
      beta = 2) is an index of right ventricular (RV) contractility, we measured RV
      pressure (P) and volume (V) and pulmonary artery pressure and flow in 10 dogs at
      baseline and after inotropic stimulation. PAMP was derived from steady-state
      data, whereas the slope (E(es)) and intercept (V(d)) of the end-systolic P-V
      relationship were derived from data obtained during vena caval occlusion.
      Inotropic stimulation increased E(es) (from 0.96 +/- 0.25 to 1.62 +/- 0.28
      mmHg/ml; P < 0.001) and V(d) (from -3.0 +/- 17.2 to 12.4 +/- 10.8 ml; P < 0.05)
      but not PAMP (from 0.24 +/- 0.10 to 0.36 +/- 0.22 mW/ml(2); P = 0.09). We found a
      strong relationship between the optimal beta-factor for preload adjustment and
      V(d). A corrected PAMP, PAMP(c) = W(max)/(V(ed) - V(d))(2), which incorporated
      the V(d) dependency, was sensitive to the inotropic changes (from 0.23 +/- 0.12
      to 0.54 +/- 0.17 mW/ml(2); P < 0.001) with a good correlation with E(es) (r =
      0.88; P < 0.001).

PMID- 12234824
TI  - Effects of omega-3 polyunsaturated fatty acids on cardiac sarcolemmal Na(+)/H(+)
      exchange.
AB  - Myocardial ischemia-reperfusion activates the Na(+)/H(+) exchanger, which induces
      arrhythmias, cell damage, and eventually cell death. Inhibition of the exchanger
      reduces cell damage and lowers the incidence of arrhythmias after ischemia
      reperfusion. The omega-3 polyunsaturated fatty acids (PUFAs) are also known to be
      cardioprotective and antiarrhythmic during ischemia-reperfusion challenge. Some
      of the action of PUFAs may occur via inhibition of the Na(+)/H(+) exchanger. The
      purpose of our study was to determine the capacity for selected PUFAs to alter
      cardiac sarcolemmal (SL) Na(+)/H(+) exchange. Cardiac membranes highly enriched
      in SL vesicles were exposed to 10-100 microM eicosapentanoic acid (EPA) or
      docosahexanoic acid (DHA). H(+)-dependent (22)Na(+) uptake was inhibited by 30
      50% after treatment with > or =50 microM EPA or > or =25 microM DHA. This was a
      specific effect of these PUFAs, because 50 microM linoleic acid or linolenic acid
      had no significant effect on Na(+)/H(+) exchange. The SL vesicles did not exhibit
      an increase in passive Na(+) efflux after PUFA treatment. In conclusion, EPA and
      DHA can potently inhibit cardiac SL Na(+)/H(+) exchange at physiologically
      relevant concentrations. This may explain, in part, their known cardioprotective
      effects and antiarrhythmic actions during ischemia-reperfusion.

PMID- 12234825
TI  - Sexual dimorphism in the complexity of cardiac pacemaker activity.
AB  - This study explored the effects of gender and aging on the complexity of cardiac
      pacemaker activity. Electrocardiogram signals were studied in normal women (n =
      240) and men (n = 240) ranging in age from 40 to 79 yr. Nonlinear analysis of
      short-term resting R-R intervals was performed using the correlation dimension
      (CD), approximate entropy (ApEn), and largest Lyapunov exponent (LLE). Evidence
      of nonlinear structure was obtained by the surrogate data test. CD, ApEn, and LLE
      were negatively correlated with age. Despite similar means and SDs of the R-R
      intervals, women had a significantly higher CD, ApEn, and LLE compared with men
      in the age strata of 40-44 and 45-49 yr. CD and ApEn were strongly (r > 0.71)
      correlated with low- and high-frequency components. We conclude that the resting
      cardiac pacemaker activity of women is more complex than that of men in middle
      age, and the gender-related difference diminishes after the age of 50 yr. The
      higher complexity implies a more comprehensive neural modulation.

PMID- 12234826
TI  - Premature excitation and onset of reentrant ventricular tachycardia.
AB  - It was hypothesized that quantitative sinus rhythm electrogram measurements could
      be used to predict conduction events that result from premature stimulation and
      reentrant ventricular tachycardia inducibility. Sinus rhythm activation and
      electrogram-duration maps were constructed from bipolar electrograms acquired at
      196-312 sites in the epicardial border zone of 43 canine hearts (25 with and 18
      without reentrant ventricular tachycardia inducible by premature stimulation).
      From these maps, lines of electrical discontinuity, where blocks would occur
      during premature excitation, were estimated. The mean error in distance between
      the estimated and actual block lines of premature excitation was 0.97 +/- 0.49
      cm. Based on the quantitative characteristics of the activation and electrogram
      duration maps and the longest block line that formed during premature excitation,
      it was possible to predict whether reentry would occur (sensitivity, 94.7%;
      specificity, 79.6%). In reentry experiments, the breakthrough-point location
      along the unidirectional arc of the block that initiated reentry was also
      predictable (mean error, 0.79 +/- 0.19 cm). Sinus rhythm measurements are useful
      to predict conduction events that result from premature stimulation and reentry
      inducibility.

PMID- 12234827
TI  - An implantable bolus infusion pump for use in freely moving, nontethered rats.
AB  - One of the current constraints on functional neuroimaging in animals is that to
      avoid movement artifacts during data acquisition, subjects need to be
      immobilized, sedated, or anesthetized. Such measures limit the behaviors that can
      be examined, and introduce the additional variables of stress or anesthetic
      agents that may confound meaningful interpretation. This study provides a
      description of the design and characteristics of a self-contained, implantable
      microbolus infusion pump (MIP) that allows triggering of a bolus injection at a
      distance in conscious, behaving rats that are not restrained or tethered. The MIP
      is externally triggered by a pulse of infrared light and allows in vivo bolus
      drug delivery. We describe application of this technology to the intravenous
      bolus delivery of iodo[(14)C]antipyrine in a freely moving animal, followed
      immediately by lethal injection, rapid removal of the brain, and analysis of
      regional cerebral blood flow tissue radioactivity with the use of
      autoradiography. The ability to investigate changes in brain activation in
      nonrestrained animals makes the MIP a powerful tool for evaluation of complex
      behaviors.

PMID- 12234828
TI  - Validation of formamide as a detubulation agent in isolated rat cardiac cells.
AB  - Kawai M, Hussain M, and Orchard CH. Am J Heart Circ Physiol 277: H603-H609, 1999
      developed a technique to detubulate rat ventricular myocytes using formamide and
      showed that detubulation results in a decrease in cell capacitance, Ca(2+)
      current density, and Ca(2+) transient amplitude. We have investigated the
      mechanism of this detubulation and possible direct effects of formamide. Staining
      ventricular cells with di-8-ANEPPS showed that the t tubule membranes remain
      inside the cell after detubulation; trapping of FITC-labeled dextran within the t
      tubules showed that detubulation occurs during formamide washout and that the t
      tubules appear to reseal within the cell. Detubulation had no effect on the
      microtubule network but resulted in loss of synchronous Ca(2+) release on
      electrical stimulation. In contrast, formamide treatment of atrial cells did not
      significantly change cell capacitance, Ca(2+) current amplitude, action potential
      configuration, the Ca(2+) transient or the response of the Ca(2+) transient to
      isoprenaline. We conclude that formamide washout induces detubulation of single
      rat ventricular myocytes, leaving the t tubules within the cell, but without
      direct effects on cell proteins that might alter cell function.

PMID- 12234829
TI  - Respiratory variations of aortic VTI: a new index of hypovolemia and fluid
      responsiveness.
AB  - In 12 mechanically ventilated and anesthetized rabbits, we investigated whether
      the magnitude of respiratory changes in the aortic velocity time integral
      (VTI(Ao)), recorded by transthoracic echocardiography (TTE) during a stepwise
      blood withdrawal and restitution, could be used as a reliable indicator of volume
      depletion and responsiveness. At each step, left and right ventricular dimensions
      and the aortic diameter and VTI(Ao) were recorded to calculate stroke volume (SV)
      and cardiac output (CO). Respiratory changes of VTI(Ao) (maximal - minimal values
      divided by their respective means) were calculated. The amount of blood
      withdrawal correlated negatively with left and right ventricular diastolic
      diameters, VTI(Ao), SV, and CO and correlated directly with respiratory changes
      of VTI(Ao). Respiratory VTI(Ao) variations (but not other parameters) at the last
      blood withdrawal step was also correlated with changes in SV after blood
      restitution (r = 0.83, P < 0.001). In conclusion, respiratory variations in
      VTI(Ao) using TTE appear to be a sensitive index of blood volume depletion and
      restitution. This dynamic parameter predicted fluid responsiveness more reliably
      than static markers of cardiac preload.

PMID- 12234830
TI  - TENS attenuates response to colon distension in paraplegic and quadriplegic rats.
AB  - Individuals with spinal cord injuries above thoracic level 6 experience episodic
      bouts of life-threatening hypertension as part of a condition termed autonomic
      dysreflexia (AD). The hypertension can be caused by stimulation of the skin,
      distension of the urinary bladder or colon, and/or muscle spasms. Transcutaneous
      electrical nerve stimulation (TENS) may reduce the severity of AD because TENS
      has been used to inhibit second-order neurons in the dorsal horn. Therefore, we
      tested the hypothesis that TENS attenuates the hemodynamic responses to colon
      distension. Eleven Wistar rats underwent spinal cord transection between thoracic
      vertebrae 4 and 5 (paraplegic, n = 6) or between cervical vertebra 7 and thoracic
      vertebra 1 (quadriplegic, n = 5). After recovery, all rats were instrumented with
      a radiotelemetry device for recording arterial pressure. Subsequently, the
      hemodynamic responses to graded colon distension were determined before and
      during TENS. During TENS the hemodynamic responses to colon distension were
      significantly attenuated. Thus TENS may be a preventive approach to reduce the
      severity of AD in paraplegic and quadriplegic individuals.

PMID- 12234831
TI  - No ischemic preconditioning in heterozygous connexin43-deficient mice.
AB  - Protein kinase Cepsilon (PKCepsilon) plays a central role in ischemic
      preconditioning (IP) in mice and rabbits, and activated PKCepsilon colocalizes
      with and phosphorylates connexin43 (Cx43) in rats and humans. Whether or not Cx43
      contributes to the mechanism(s) of IP in vivo is yet unknown. Therefore, wild
      type (n = 8) and heterozygous Cx43-deficient mice (n = 8) were subjected to 30
      min occlusion and 120 min reperfusion of the left anterior descending coronary
      artery. IP was induced by one cycle of 5 min occlusion and 10 min reperfusion (n
      = 8/8 mice) before the sustained occlusion. Infarct size was reduced by IP in
      wild-type mice [11.3 +/- 3.4% vs. 23.7 +/- 7.2% of the left ventricle (LV), P <
      0.05] but not in Cx43-deficient mice (26.0 +/- 6.0% vs. 25.1 +/- 3.8% of LV).
      Also, three cycles of 5 min occlusion and 10 min reperfusion (n = 5) did not
      induce protection in Cx43-deficient mice (27.6 +/- 5.5 % of LV). Thus Cx43
      contributes to the protection of IP in mice in vivo.

PMID- 12234832
TI  - Endogenous reactive oxygen species is an important mediator of miconazole
      antifungal effect.
AB  - We investigated the significance of endogenous reactive oxygen species (ROS)
      produced by fungi treated with miconazole. ROS production in Candida albicans was
      measured by a real-time fluorogenic assay. The level of ROS production was
      increased by miconazole at the MIC (0.125 micro g/ml) and was enhanced further in
      a dose-dependent manner, with a fourfold increase detected when miconazole was
      used at 12.5 micro g/ml. This increase in the level of ROS production was
      completely inhibited by pyrrolidinedithiocarbamate (PDTC), an antioxidant, at 10
      micro M. In a colony formation assay, the decrease in cell viability associated
      with miconazole treatment was significantly prevented by addition of PDTC.
      Moreover, the level of ROS production by 10 clinical isolates of Candida species
      was inversely correlated with the miconazole MIC (r = -0.8818; P < 0.01). These
      results indicate that ROS production is important to the antifungal activity of
      miconazole.

PMID- 12234833
TI  - Discovery of a novel and potent class of FabI-directed antibacterial agents.
AB  - Bacterial enoyl-acyl carrier protein (ACP) reductase (FabI) catalyzes the final
      step in each elongation cycle of bacterial fatty acid biosynthesis and is an
      attractive target for the development of new antibacterial agents. High
      throughput screening of the Staphylococcus aureus FabI enzyme identified a novel,
      weak inhibitor with no detectable antibacterial activity against S. aureus.
      Iterative medicinal chemistry and X-ray crystal structure-based design led to the
      identification of compound 4 [(E)-N-methyl-N-(2-methyl-1H-indol-3-ylmethyl)-3-(7
      oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide], which is 350-fold more
      potent than the original lead compound obtained by high-throughput screening in
      the FabI inhibition assay. Compound 4 has exquisite antistaphylococci activity,
      achieving MICs at which 90% of isolates are inhibited more than 500 times lower
      than those of nine currently available antibiotics against a panel of multidrug
      resistant strains of S. aureus and Staphylococcus epidermidis. Furthermore,
      compound 4 exhibits excellent in vivo efficacy in an S. aureus infection model in
      rats. Biochemical and genetic approaches have confirmed that the mode of
      antibacterial action of compound 4 and related compounds is via inhibition of
      FabI. Compound 4 also exhibits weak FabK inhibitory activity, which may explain
      its antibacterial activity against Streptococcus pneumoniae and Enterococcus
      faecalis, which depend on FabK and both FabK and FabI, respectively, for their
      enoyl-ACP reductase function. These results show that compound 4 is
      representative of a new, totally synthetic series of antibacterial agents that
      has the potential to provide novel alternatives for the treatment of S. aureus
      infections that are resistant to our present armory of antibiotics.

PMID- 12234834
TI  - Biochemical and genetic characterization of the vanC-2 vancomycin resistance gene
      cluster of Enterococcus casseliflavus ATCC 25788.
AB  - The vanC-2 cluster of Enterococcus casseliflavus ATCC 25788 consisted of five
      genes (vanC-2, vanXY(C-2), vanT(C-2), vanR(C-2), and vanS(C-2)) and shared the
      same organization as the vanC cluster of E. gallinarum BM4174. The proteins
      encoded by these genes displayed a high degree of amino acid identity to the
      proteins encoded within the vanC gene cluster. The putative D,D-dipeptidase-D,D
      carboxypeptidase, VanXY(C-2), exhibited 81% amino acid identity to VanXY(C), and
      VanT(C-2) displayed 65% amino acid identity to the serine racemase, VanT. VanR(C
      2) and VanS(C-2) displayed high degrees of identity to VanR(C) and VanS(C),
      respectively, and contained the conserved residues identified as important to
      their function as a response regulator and histidine kinase, respectively.
      Resistance to vancomycin was expressed inducibly in E. casseliflavus ATCC 25788
      and required an extended period of induction. Analysis of peptidoglycan
      precursors revealed that UDP-N-acetylmuramyl-L-Ala-delta-D-Glu-L-Lys-D-Ala-D-Ser
      could not be detected until several hours after the addition of vancomycin, and
      its appearance coincided with the resumption of growth. The introduction of
      additional copies of the vanT(C-2) gene, encoding a putative serine racemase, and
      the presence of supplementary D-serine in the growth medium both significantly
      reduced the period before growth resumed after addition of vancomycin. This
      suggested that the availability of D-serine plays an important role in the
      induction process.

PMID- 12234835
TI  - Multidrug pump inhibitors uncover remarkable activity of plant antimicrobials.
AB  - Plant antimicrobials are not used as systemic antibiotics at present. The main
      reason for this is their low level of activity, especially against gram-negative
      bacteria. The reported MIC is often in the range of 100 to 1,000 micro g/ml,
      orders of magnitude higher than those of common broad-spectrum antibiotics from
      bacteria or fungi. Major plant pathogens belong to the gram-negative bacteria,
      which makes the low level of activity of plant antimicrobials against this group
      of microorganisms puzzling. Gram-negative bacteria have an effective permeability
      barrier, comprised of the outer membrane, which restricts the penetration of
      amphipathic compounds, and multidrug resistance pumps (MDRs), which extrude
      toxins across this barrier. It is possible that the apparent ineffectiveness of
      plant antimicrobials is largely due to the permeability barrier. We tested this
      hypothesis in the present study by applying a combination of MDR mutants and MDR
      inhibitors. A panel of plant antimicrobials was tested by using a set of bacteria
      representing the main groups of plant pathogens. The human pathogens Pseudomonas
      aeruginosa, Escherichia coli, and Salmonella enterica serovar Typhimurium were
      also tested. The results show that the activities of the majority of plant
      antimicrobials were considerably greater against the gram-positive bacteria
      Staphylococcus aureus and Bacillus megaterium and that disabling of the MDRs in
      gram-negative species leads to a striking increase in antimicrobial activity.
      Thus, the activity of rhein, the principal antimicrobial from rhubarb, was
      potentiated 100- to 2,000-fold (depending on the bacterial species) by disabling
      the MDRs. Comparable potentiation of activity was observed with plumbagin,
      resveratrol, gossypol, coumestrol, and berberine. Direct measurement of the
      uptake of berberine, a model plant antimicrobial, confirmed that disabling of the
      MDRs strongly increases the level of penetration of berberine into the cells of
      gram-negative bacteria. These results suggest that plants might have developed
      means of delivering their antimicrobials into bacterial cells. These findings
      also suggest that plant antimicrobials might be developed into effective, broad
      spectrum antibiotics in combination with inhibitors of MDRs.

PMID- 12234836
TI  - Mutations in 23S rRNA account for intrinsic resistance to macrolides in
      Mycoplasma hominis and Mycoplasma fermentans and for acquired resistance to
      macrolides in M. hominis.
AB  - The mechanisms of intrinsic resistance of Mycoplasma hominis to 14- and 15
      membered macrolides were investigated in comparison with those of M. pneumoniae,
      which is naturally susceptible to macrolides. Radiolabeled erythromycin was not
      accumulated by M. hominis PG21, but addition of an ABC transporter inhibitor
      increased the level of erythromycin uptake more than two times, suggesting the
      existence of an active efflux process. The affinity of [(14)C]erythromycin to
      ribosomes isolated from M. hominis was dramatically reduced relative to that to
      ribosomes isolated from M. pneumoniae. The nucleotide sequences of 23S rRNA of
      both ribosomal operons rrnA and rrnB and ribosomal proteins L4 and L22 of M.
      hominis were obtained. Compared to the sequence of M. pneumoniae, M. hominis
      harbored a G2057A transition in its 23S rRNA sequence, as did M. fermentans,
      another mycoplasma that is erythromycin resistant. An additional C2610U change
      was also found in the sequence of M. hominis. Moreover, two M. hominis clinical
      isolates with acquired resistance to 16-membered macrolides were examined for
      mutations in domain II and domain V of 23S rRNA and in ribosomal proteins L4 and
      L22. Compared to the sequence of reference strain PG21, one isolate harbored a
      A2059G transition and a C2611U transition in one of the two rrn operons, while
      the other one was mutated only at position 2059, also on the same operon. No
      mutation was found in the two ribosomal protein sequences. Overall, the present
      study is an exhaustive characterization of the intrinsic resistance of M. hominis
      to 14- and 15-membered macrolides and the first description of mycoplasma
      clinical isolates resistant to macrolide, lincosamide, and streptogramin
      antibiotics harboring a mutation at position 2611 in the 23S rRNA.

PMID- 12234837
TI  - The carboxyl terminus of peptidoglycan stem peptides is a determinant for
      methicillin resistance in Staphylococcus aureus.
AB  - A mecA-containing Staphylococcus aureus strain was grown in the presence of high
      concentrations of D-serine, D-threonine, and D-phenylalanine. These growth
      conditions resulted in the replacement of the carboxyl-terminal (fifth) D-alanine
      residue of peptidoglycan stem peptides with the D-amino acid present in the
      growth medium and a reduced ability to grow in the presence of methicillin. The
      most dramatic effect was seen with D-serine. With 32 mM D-serine, strains that
      had been able to grow in the presence of 800 micro g of methicillin per ml were
      only able to grow in the presence of less than 50 micro g/ml. The results also
      suggest that in S. aureus vancomycin resistance mediated through the
      incorporation of precursors not terminating in D-alanyl-D-alanine would be
      mutually exclusive with expression of mecA-mediated methicillin resistance.

PMID- 12234838
TI  - Beta-lactamases in ampicillin-resistant Escherichia coli isolates from foods,
      humans, and healthy animals.
AB  - TEM-, SHV-, and OXA-type beta-lactamases were studied by PCR with 124 ampicillin
      resistant (AMP(r)) Escherichia coli isolates recovered from foods of animal
      origin (n = 20) and feces of humans (n = 49) and healthy animals (n = 55). PCR
      showed that 103 isolates were positive for TEM and negative for SHV and OXA.
      Three E. coli isolates showed a positive reaction for OXA, and one showed a
      positive reaction for SHV. The remaining 17 E. coli isolates were negative for
      the three enzymes by PCR. Fifty-seven of the 103 bla(TEM) amplicons were
      sequenced. Different molecular variants of bla(TEM-1) were found in 52 isolates:
      bla(TEM-1a) (n = 9), bla(TEM-1b) (n = 36), bla(TEM-1c) (n = 6), and bla(TEM-1f)
      (n = 1). Four inhibitor-resistant TEM (IRT) beta-lactamase-encoding genes were
      also detected: bla(TEM-30c) (IRT-2), bla(TEM-34b) (IRT-6), bla(TEM-40b) (IRT-11),
      and bla(TEM-51a) (IRT-15). A new bla(TEM) gene, named bla(TEM-95b), which showed
      a mutation in amino acid 145 (P-->A) was detected. It was found in a food isolate
      of chicken origin (AMP(r), amoxicillin-clavulanic acid susceptible). The promoter
      region in 24 bla(TEM) amplicons was analyzed, and the weak P3 promoter was found
      in 23 of them (bla(TEM-1) in 20 amplicons and bla(TEM-51a), bla(TEM-30c), and
      bla(TEM-95b) in 1 amplicon each). The strong Pa/Pb promoter was found only in the
      bla(TEM-34b) gene. No extended-spectrum beta-lactamases were detected. Mutations
      at position -42 or -32 in the ampC gene promoter were demonstrated in 4 of 10 E.
      coli isolates for which the cefoxitin MIC was >/=16 micro g/ml. Different
      variants of bla(TEM-1) and IRT bla(TEM) genes were found among the AMP(r) E. coli
      isolates from foods and the feces of humans and healthy animals, and a new gene,
      bla(TEM-95b) (P3), was detected.

PMID- 12234839
TI  - Comparison of the in vitro activity of the glycylcycline tigecycline (formerly
      GAR-936) with those of tetracycline, minocycline, and doxycycline against
      isolates of nontuberculous mycobacteria.
AB  - We compared the in vitro activity of the glycylcycline tigecycline (formerly GAR
      936) with those of tetracycline, doxycycline, and minocycline by broth
      microdilution against 76 isolates belonging to seven species of rapidly growing
      mycobacteria (RGM) and 45 isolates belonging to five species of slowly growing
      nontuberculous mycobacteria (NTM). By using a resistance breakpoint of >4 micro
      g/ml for tigecycline and >8 micro g/ml for tetracycline, all RGM were highly
      susceptible to tigecycline, with inhibition of 50% of isolates at < or =0.12
      micro g/ml and inhibition of 90% of isolates at 0.25 micro g/ml for Mycobacterium
      abscessus and inhibition of both 50 and 90% of isolates at < or =0.12 micro g/ml
      for M. chelonae and the M. fortuitum group. The MICs of tigecycline were the same
      for tetracycline-resistant and -susceptible strains, and RGM isolates were 4- to
      11-fold more susceptible to tigecycline than to the tetracyclines. In contrast,
      no slowly growing NTM were susceptible to tigecycline, and isolates of M. marinum
      and M. kansasii were less susceptible to this agent than to minocycline. This new
      antimicrobial offers exciting therapeutic potential for the RGM, especially for
      isolates of the M. chelonae-M. abscessus group, against which the activities of
      the currently available drugs are limited.

PMID- 12234840
TI  - In vitro antimicrobial activity of GSQ1530, a new heteroaromatic polycyclic
      compound.
AB  - GSQ1530 is a compound derived from a newly identified class of antibiotics
      referred to as heteroaromatic polycyclic (HARP) antibiotics. The aim of this
      study was to assess the in vitro antimicrobial activity of GSQ1530. By using an
      NCCLS broth microdilution assay, the activities of GSQ1530 and other antibiotics
      were coevaluated against 215 clinical isolates. The MICs at which 90% of isolates
      are inhibited (MIC(90)s) of GSQ1530 for methicillin-susceptible Staphylococcus
      aureus and methicillin-resistant S. aureus (MRSA) were 2 and 4 micro g/ml,
      respectively. The MIC(90)s of GSQ1530 for the streptococci tested were 2 micro
      g/ml or less, regardless of their susceptibilities to other antibiotics. The
      MIC(90) of GSQ1530 for the enterococci tested (including vancomycin-resistant
      enterococci) was 4 micro g/ml. No cross-resistance was found between GSQ1530 and
      other known antibiotics. In a separate assay, GSQ1530 demonstrated excellent
      activity against vancomycin-intermediate-susceptible staphylococci (MIC(90), 1
      micro g/ml). The minimal bactericidal concentration test was conducted with 73
      clinical isolates; GSQ1530 was cidal against streptococci and staphylococci but
      static against enterococci. An in vitro killing kinetic study revealed a time
      dependent profile, with at least a 3-log reduction of bacterial growth within 6 h
      after exposure to four times the MICs of GSQ1530 for both S. aureus and
      Streptococcus pneumoniae. The checkerboard study showed that GSQ1530 had a
      synergistic interaction with rifampin against MRSA. The test medium was found to
      have little effect on in vitro antimicrobial potency. The MICs of GSQ1530 for
      gram-positive cocci were 4- to 32-fold higher in the presence of serum proteins.
      GSQ1530 has high levels of plasma protein binding (91 and 89% for rat and human
      plasma, respectively). These preliminary results demonstrate that GSQ1530, a
      representative compound of our novel HARP antibiotics, has broad-spectrum
      activity against gram-positive bacteria. This novel class of antibacterial
      compounds is profiled in vivo to assess the therapeutic potential in humans.
      Ongoing in vivo studies will assess whether this class of molecules has promising
      in vivo efficacy and safety profiles.

PMID- 12234841
TI  - Effect of prolonged fluconazole treatment on Candida albicans in diffusion
      chambers implanted into mice.
AB  - Fluconazole is an azole agent with primarily fungistatic activity in standard in
      vitro susceptibility tests. The present study was undertaken to develop a
      diffusion chamber model system in mice in order to study the in vivo effects of
      prolonged fluconazole treatment on Candida albicans. Chambers containing 100 C.
      albicans yeast cells were implanted subcutaneously on the flanks of C57BL/6 mice
      and were then retrieved 6 or 14 weeks later (after fluconazole treatment for 4 or
      12 weeks, respectively). Leukocyte counts demonstrated that implantation of the
      chambers did elicit an inflammatory response but that only small numbers of
      inflammatory cells were able to enter the chamber interior. Treatment with
      fluconazole at 10 mg/kg of body weight/day for 12 weeks not only reduced the
      numbers of viable organisms within the chambers compared to those in untreated
      mice (mean +/- standard deviation of log(10) CFU of 0.7 +/- 1.2 versus 2.3 +/-
      2.0; P < 0.001 by the Bonferroni test) but also increased the numbers of chambers
      that became sterile over the treatment period (14 of 16 versus 6 of 19; P =
      0.0009 by the chi-square test). However, treatment for only 4 weeks had minimal
      effects on the numbers of chamber CFU, and none of the chambers became sterile
      during this period. Distribution of retrieved organisms between interior fluid
      and the chamber filters was approximately equal in all the treatment groups. This
      model system appears to be useful for evaluating the effects of antifungal drugs
      over prolonged periods in vivo. Its use in the present study demonstrates that
      fluconazole can increase the rate of sterilization of C. albicans foci that are
      protected from the host's inflammatory response.

PMID- 12234842
TI  - 16alpha-bromoepiandrosterone, an antimalarial analogue of the hormone
      dehydroepiandrosterone, enhances phagocytosis of ring stage parasitized
      erythrocytes: a novel mechanism for antimalarial activity.
AB  - Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S), which are the most
      abundant hormones secreted by the adrenal cortex and are present in plasma at
      approximately 6 micro M, as well as their analogue, 16alpha-bromoepiandrosterone
      (EPI), exerted antimalarial activities against two chloroquine-sensitive
      Plasmodium falciparum strains (Palo Alto, 50% inhibitory concentration [IC(50)]
      of EPI, 4.8 +/- 0.68 micro M; T996/86, IC(50) of EPI, 7.5 +/- 0.91 micro M, and
      IC(50) of DHEA-S, 19 +/- 2.6 micro M) and one mildly chloroquine-resistant strain
      (FCR-3, IC(50) of EPI, 6.5 +/- 1.01 micro M). Both EPI and DHEA/DHEA-S are potent
      inhibitors of glucose-6-phosphate dehydrogenase (G6PD), and G6PD deficiency is
      known to exert antimalaria protection via enhanced opsonization and phagocytosis
      of rings, the early forms of the parasite. Plasma-compatible antimalarial EPI
      concentrations did not inhibit G6PD activity and did not induce ring opsonization
      by immunoglobulin G and complement fragments, as observed in G6PD deficiency, but
      nevertheless remarkably stimulated ring phagocytosis. Plasma-compatible, low
      micromolar concentrations of EPI induced exposure on the ring surface of
      phosphatidylserine, a signal for phagocytic removal independent of opsonization.
      We propose that enhanced ring phagocytosis due to exposure of negatively charged
      membrane phospholipids may explain the antimalarial activity of EPI.

PMID- 12234843
TI  - Bactericidal effect and pharmacodynamics of cethromycin (ABT-773) in a murine
      pneumococcal pneumonia model.
AB  - Cethromycin (ABT-773), a new ketolide, possesses potent in vitro activity against
      Streptococcus pneumoniae. The objective of this study was to investigate the in
      vivo bactericidal activity of cethromycin against macrolide-susceptible and 
      resistant S. pneumoniae in a murine pneumonia model and to describe the
      pharmacodynamic (PD) profile of cethromycin. Eight (two macrolide susceptible,
      six macrolide resistant) clinical isolates of S. pneumoniae were investigated.
      Cyclophosphamide administration rendered ICR mice transiently neutropenic prior
      to intratracheal inoculation with 0.05 ml of an S. pneumoniae suspension
      containing 10(7) to 10(8) CFU/ml. Oral cethromycin was initiated 12 to 14 h
      postinoculation over a dosage range of 0.1 to 800 mg/kg of body weight/day. Lungs
      from seven to eight mice per treatment and control groups were collected at 0 and
      24 h posttherapy to assess bacterial density. The cumulative mortality (n = 12 to
      13) was assessed at 120 h (end of therapy) and at 192 h (3 days posttherapy).
      Recovery of pneumococci from the lungs of infected animals prior to the
      initiation of therapy ranged from 4.6 to 7.2 log(10) CFU. Growth in untreated
      control animals over a 24-h study period increased 0.3 to 2.7 log(10) CFU.
      Cethromycin demonstrated a substantial bactericidal effect, regardless of
      macrolide susceptibility. Correlation between changes in bacterial density (24 h)
      and survival over both 120 and 192 h were statistically significant. All three PD
      parameters demonstrated a significant correlation with changes in log(10)
      CFU/lung (Spearman's correlation coefficient, P < 0.001); however, the goodness
      of fit as assessed with the maximum effect (E(max)) model revealed that the
      maximum concentration of free drug in serum (C(max free))/MIC and the area under
      the free drug concentration-time curve (AUC(free))/MIC best explained the
      relationship between drug exposure and reductions in viable bacterial counts.
      These data reveal that an approximate cethromycin AUC(free)/MIC of 50 or C(max
      free)/MIC of 1 results in bacteriostatic effects, while higher values (twofold)
      maximize survival.

PMID- 12234844
TI  - Bactericidal activity of rifampin-amikacin against Mycobacterium ulcerans in
      mice.
AB  - To identify the most active curative treatment of Buruli ulcer, two regimens
      incorporating the use of rifampin (RIF) were compared with the use of RIF alone
      in a mouse footpad model of Mycobacterium ulcerans infection. Treatments began
      after footpad swelling from infection and continued for 12 weeks with five doses
      weekly of one of the following regimens: (i) 10 mg of RIF/kg alone; (ii) 10 mg of
      RIF/kg and 100 mg of amikacin (AMK)/kg; and (iii) 10 mg of RIF/kg, 100 mg of
      clarithromycin (CLR)/kg, and 50 mg of sparfloxacin (SPX)/kg. The activity of each
      regimen was assessed in terms of the reduction of the average lesion index and
      acid-fast bacillus (AFB) and CFU counts. All three regimens displayed various
      degrees of bactericidal activity against M. ulcerans. The ranking of bactericidal
      activity was found to be as follows: RIF-AMK > RIF-CLR-SPX > RIF. RIF-AMK was
      able to cure M. ulcerans-infected mice and prevent relapse 26 weeks after
      completion of treatment. To determine the impact of different rhythms of
      administration of RIF-AMK on the suppression of M.ulcerans growth, mice were
      given the RIF-AMK combination for 4 weeks but doses were administered either 5
      days a week or twice or once weekly. After completion of treatment, the mice were
      kept under supervision for 30 additional weeks. M. ulcerans was considered to
      have grown in the footpad if swelling was visually observed and harvests
      contained more than 5 x 10(5) AFB per footpad. The proportion of mice in which
      growth of M. ulcerans occurred, irrespective of drug dosage, was compared with
      the control mice to determine the proportion of M. ulcerans killed. Each dosage
      of RIF-AMK was bactericidal for M. ulcerans (P < 0.001), but the effect was
      significantly stronger in mice treated 5 days per week. The promising results of
      RIF-AMK treatment in M. ulcerans-infected mice support the clinical trial that is
      currently in progress under World Health Organization auspices in Ghana.

PMID- 12234845
TI  - Ligands of the peripheral benzodiazepine receptor are potent inhibitors of
      Plasmodium falciparum and Toxoplasma gondii in vitro.
AB  - The increase in resistance of the malaria parasite Plasmodium falciparum to
      currently available drugs demands the development of new antimalarial agents. In
      this quest, we have found that ligands to the peripheral benzodiazepine receptor
      such as flurazepam, an agonist of the benzodiazepine family, and PK11195, an
      antagonist derived from isoquinoline, were active against Plasmodium falciparum.
      These two compounds effectively and rapidly inhibited parasite growth in vitro,
      irrespective of parasite resistance to chloroquine and mefloquine. Treatment with
      both drugs induced a sharp and consistent decline in parasitemia, a complete
      inhibition of parasite replication, and the destruction of parasites within the
      host red blood cells. Using electron microscopy, we showed that dramatic
      morphological changes, involving swollen endoplasmic reticulum and the reduction
      of hemozoin, were consistent with parasite death. The potent activities of
      flurazepam and PK11195 were also evaluated for antagonist or synergistic effects
      with currently used antimalarial drugs such as chloroquine and mefloquine.
      Moreover, flurazepam was found to be active against Toxoplasma gondii, another
      member of the phylum Apicomplexa. Taken together, our results indicated that
      benzodiazepines could be considered promising candidates in the treatment of both
      malaria and toxoplasmosis.

PMID- 12234846
TI  - Itraconazole preexposure attenuates the efficacy of subsequent amphotericin B
      therapy in a murine model of acute invasive pulmonary aspergillosis.
AB  - Antagonism has been described in vitro and in vivo for azole-polyene combinations
      against Aspergillus species. Using an established murine model of invasive
      pulmonary aspergillosis, we evaluated the efficacy of several amphotericin B
      (AMB) dosages given alone or following preexposure to itraconazole (ITC). Mice
      were immunosuppressed with cortisone acetate and cyclophosphamide. During
      immunosuppression, animals were administered either ITC solution (50 mg/kg of
      body weight) or saline by oral gavage twice daily for 3 days prior to infection.
      Infection was induced by intranasally inoculating mice with a standardized
      conidial suspension (1 x 10(8) CFU/ml) of Aspergillus fumigatus strain AF 293.
      AMB was then administered by daily intraperitoneal injections (0.25, 0.5, 1.0,
      and 3.0 mg/kg) starting 24 h after inoculation and continuing for a total of 72
      h. Drug pharmacokinetics of AMB and ITC in plasma were determined by high
      performance liquid chromatography. Four different endpoints were used to examine
      the efficacy of antifungal therapy: (i) viable counts from harvested lung tissue
      (in CFU per milliliter), (ii) the whole-lung chitin assay, (iii) mortality at 96
      h, and (iv) histopathology of representative lung sections. At AMB doses of >0.5
      mg/kg/day, fewer ITC-preexposed mice versus non-ITC-preexposed mice were alive at
      96 h (0 to 20 versus 60%, respectively). At all time points, the fungal lung
      burden was consistently and significantly higher in animals preexposed to ITC, as
      measured by the CFU counts (P = 0.001) and the chitin assay (P = 0.03). Higher
      doses of AMB did not overcome this antagonism. ITC preexposure was associated
      with poorer mycological efficacy and survival in mice treated subsequently with
      AMB for invasive pulmonary aspergillosis.

PMID- 12234847
TI  - Biochemical-genetic analysis and distribution of DES-1, an Ambler class A
      extended-spectrum beta-lactamase from Desulfovibrio desulfuricans.
AB  - Desulfovibrio spp. are gram-negative anaerobes phylogenetically related to
      Bacteroides spp., which are rarely isolated and which are mostly isolated from
      intra-abdominal abscesses. Desulfovibrio desulfuricans clinical isolate D3 had a
      clavulanic acid-inhibited beta-lactam resistance profile and was resistant to
      some expanded-spectrum cephalosporins. A beta-lactamase gene, bla(DES-1), was
      cloned from whole-cell DNA of isolate D3 and expressed in Escherichia coli.
      Purified beta-lactamase DES-1, with a pI value of 9.1, had a relative molecular
      mass of ca. 31 kDa and a mature protein of 288 amino acids. DES-1 was distantly
      related to Ambler class A beta-lactamases and most closely related to PenA from
      Burkholderia pseudomallei (48% amino acid identity). It was weakly related to
      class A beta-lactamases CblA, CepA, CfxA, and CfxA2 from other anaerobic species,
      Bacteroides spp. and Prevotella intermedia. Its hydrolysis spectrum included
      amino- and ureidopenicillins, narrow-spectrum cephalosporins, ceftriaxone, and
      cefoperazone. bla(DES-1)-like genes were not identified in phylogenetically
      related Desulfovibrio fairfieldensis isolates. However, they were found in some
      but not all D. desulfuricans strains, thus suggesting that these genes may be
      present in a given D. desulfuricans subspecies.

PMID- 12234848
TI  - EBR-1, a novel Ambler subclass B1 beta-lactamase from Empedobacter brevis.
AB  - Empedobacter brevis (formerly designated Flavobacterium breve) is a gram-negative
      aerobe involved in nosocomial infections. The Ambler class B beta-lactamase gene
      bla(EBR-1) was cloned and expressed in Escherichia coli from E. brevis clinical
      strain ASS-1, which had reduced susceptibility to expanded-spectrum
      cephalosporins and carbapenems. Purified beta-lactamase EBR-1 hydrolyzed
      penicillins, cephalosporins, and carbapenems efficiently but not aztreonam.
      Kinetic parameters of EBR-1 were similar to those of class B enzymes such as
      BlaB, IND-2, and GOB-1 identified from other Flavobacteriaceae species, except
      for meropenem, which was more hydrolyzed by beta-lactamase GOB-1. EBR-1, with a
      pI of 8.0 and a relative molecular mass of ca. 25 kDa, was classified in
      functional subgroup 3a, which includes most of the class B beta-lactamases. EBR
      1, which belongs to molecular subclass B1 of metalloenzymes, shares 58, 57, and
      42% amino acid identity with the most closely related beta-lactamases, IND-1/IND
      2 from Chryseobacterium indologenes, CGB-1 from Chryseobacterium gleum, and BlaB
      from Chryseobacterium meningosepticum, respectively.

PMID- 12234849
TI  - Intracellular accumulation of human immunodeficiency virus protease inhibitors.
AB  - Intracellular accumulation of the protease inhibitors (PIs) saquinavir (SQV),
      ritonavir (RTV), and indinavir (IDV) was determined in 50 human immunodeficiency
      virus-positive patients. Following extraction, PIs were quantified by mass
      spectrometry. Paired plasma and intracellular samples were collected over a full
      dosing interval from patients (13 on SQV, 6 on RTV, 8 on IDV, 16 on SQV plus RTV,
      7 on IDV plus RTV) with a plasma viral load of <400 copies/ml. Data were
      expressed as intracellular/plasma drug concentration ratios. A hierarchy of
      intracellular accumulation was demonstrated by the following medians: 9.45 for
      SQV > 1.00 for RTV > 0.51 for IDV. Coadministration of RTV did not boost ratios
      of SQV or IDV within the cell or in plasma, although absolute plasma and
      intracellular SQV concentrations were increased by RTV. Seven individuals
      receiving SQV in hard-gel capsule form (median, 32 months) had higher
      intracellular/plasma drug ratios than all other patients receiving SQV (median,
      17.62 versus 4.83; P = 0.04), despite consistently low plasma SQV concentrations.
      How this occurs may provide insight into the mechanisms that limit adequate drug
      penetration into sanctuary sites.

PMID- 12234850
TI  - Comparative evaluation of a new fluorescent carboxyfluorescein diacetate-modified
      microdilution method for antifungal susceptibility testing of Candida albicans
      isolates.
AB  - This report presents a fluorescent carboxyfluorescein diacetate (CFDA)-modified
      microdilution method used for the susceptibility testing of Candida albicans to
      amphotericin B, fluconazole, ketoconazole, itraconazole, voriconazole, and
      flucytosine. Four different broth microdilution susceptibility testing methods
      were simultaneously evaluated at 24 and 48 h. The MICs determined using the CFDA
      modified method (MIC(cfda)) were compared to those obtained by the standard broth
      microdilution method (MIC(visual)) and a procedure employing the indicator Alamar
      blue (MIC(alamar)). The reference MIC was determined visually as recommended by
      the NCCLS M27-A protocol, and then quantified spectrophotometrically following
      agitation (MIC(spec)). The CFDA-modified microdilution method was demonstrated to
      effectively determine the MICs for all the antifungal drugs tested at both 24 and
      48 h. The results from both the MIC(spec) and MIC(cfda) methods yielded >80%
      agreement within +/-1 dilution and >90% agreement within +/-2 dilutions at 24 h
      in comparison to the reference MIC(visual) method, respectively. The trailing
      growth phenomenon that occurs with azole antifungal drugs and many strains of C.
      albicans did not inhibit the effectiveness of the MIC(spec) and MIC(cfda)
      methods. The MIC(spec) and MIC(cfda) methods shared 92.8% agreement within +/-1
      dilution at 24 h and 87.6% agreement within +/-1 dilution at 48 h.

PMID- 12234851
TI  - Imiquimod 5-percent cream does not alter the natural history of recurrent herpes
      genitalis: a phase II, randomized, double-blind, placebo-controlled study.
AB  - Present strategies for control of herpes genitalis recurrences require multiple
      daily doses of antiviral medication. Imiquimod, an immune response modifier,
      induces alpha interferon and interleukin-12; application in the presence of local
      herpes antigens during a recurrence may augment herpes simplex virus (HSV)
      specific cell-mediated immunity. To test this theory, we performed a randomized,
      double-blind, placebo-controlled study of imiquimod 5% cream to assess safety and
      efficacy for decreasing recurrences. Patients with six or more recurrences of
      herpes genitalis per year applied study cream (imiquimod or placebo) to lesions
      one, two, or three times per week for 3 weeks for each recurrence during a 16
      week treatment period. This was followed by a 16-week observation period. Of 124
      patients randomized to the study, 103 completed the treatment period and 93
      completed the observation period. The median times to first genital herpes
      recurrence were 53 days for those receiving placebo (n = 30) and 54, 60, and 64
      days for those receiving imiquimod one time per week (n = 34), two times per week
      (n = 32), and three times per week (n = 28), respectively. The median annualized
      recurrence rates during the treatment period were 3.8, 4.9, 3.2, and 3.1,
      respectively. There were no statistically significant differences in the time to
      first recurrence or in the annualized recurrence rate between the imiquimod and
      placebo groups in either the treatment or the observation period. A trend in
      increased rates of local adverse events at the application site and a delay in
      lesion healing with more frequent dosing suggested a pharmacologic effect.
      Although clinical efficacy has been observed for imiquimod in other conditions in
      which a TH1-type immune response may be beneficial, including other viral
      infections such as those caused by human papillomavirus, no apparent effect on
      the short-term natural history of herpes genitalis recurrences was observed.

PMID- 12234852
TI  - DNA sequence analysis of DNA gyrase and DNA topoisomerase IV quinolone resistance
      determining regions of Salmonella enterica serovar Typhi and serovar Paratyphi A.
AB  - The mutations that are responsible for fluoroquinolone resistance in the gyrA,
      gyrB, parC, and parE genes of Salmonella enterica serovar Typhi and serovar
      Paratyphi A were investigated. The sequences of the quinolone resistance
      determining region of the gyrA gene in clinical isolates which showed decreased
      susceptibilities to fluoroquinolones had a single mutation at either the Ser-83
      or the Asp-87 codon, and no mutations were found in the gyrB, parC, and parE
      genes.

PMID- 12234853
TI  - Mutations in the aph(2")-Ic gene are responsible for increased levels of
      aminoglycoside resistance.
AB  - Random PCR mutagenesis of the enterococcal aph(2")-Ic gene followed by selection
      for mutant enzymes that confer enhanced levels of aminoglycoside resistance
      resulted in mutants of APH(2")-Ic with His-258-Leu and Phe-108-Leu substitutions,
      all of which conferred rises in the MICs of several aminoglycosides. The mutated
      residues are located outside conserved regions of aminoglycoside
      phosphotransferases.

PMID- 12234854
TI  - A resistance-nodulation-cell division family xenobiotic efflux pump in an
      obligate anaerobe, Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis, a gram-negative obligate anaerobe, contains two
      homologs of an Escherichia coli resistance-nodulation-cell division-type
      multidrug exporter gene, acrB, in putative operons, together with homologs of
      membrane fusion protein gene acrA and outer membrane channel gene tolC. MIC
      determination and accumulation assays with mutants with disruptions of one or
      more genes showed that one cluster, named xepCAB, pumped out multiple agents
      including rifampin, puromycin, and ethidium bromide.

PMID- 12234855
TI  - Penicillin-binding protein 1A, 2B, and 2X alterations in Canadian isolates of
      penicillin-resistant Streptococcus pneumoniae.
AB  - Alterations within the penicillin-binding domain of penicillin-binding protein
      (PBP) genes pbp1a, pbp2b, and pbp2x were determined for 15 Canadian isolates of
      Streptococcus pneumoniae. All penicillin-nonsusceptible S. pneumoniae isolates
      showed a variety of PBP 2X substitutions and contained a Thr445-Ala change after
      the PBP 2B SSN motif. Only isolates for which penicillin MICs were > or =0.5
      micro g/ml had PBP 1A alterations near the STMK and SRN motifs. Sequence analysis
      revealed identical PBP 1A, PBP 2B, and PBP 2X substitution patterns among all
      isolates for which penicillin MICs were > or =1 micro g/ml.

PMID- 12234856
TI  - -11 Mutation in the ampC promoter increasing resistance to beta-lactams in a
      clinical Escherichia coli strain.
AB  - A mutation was discovered in the Pribnow box of the ampC promoter in a clinical
      Escherichia coli strain. This -11 C-to-T transition created a perfect homology
      with the -10 consensus sequence. The new promoter was cloned upstream of the cat
      gene of pKK232-8 and induced a sixfold increase in promoter strength.

PMID- 12234857
TI  - Prospective, multicenter surveillance study of Candida glabrata: fluconazole and
      itraconazole susceptibility profiles in bloodstream, invasive, and colonizing
      strains and differences between isolates from three urban teaching hospitals in
      New York City (Candida Susceptibility Trends Study, 1998 to 1999).
AB  - Since the 1990s, the substantial increase in the rate of Candida glabrata
      infections has become a serious problem. As most C. glabrata infections arise
      from the host's endogenous microflora, the present prospective, multicenter
      analysis included all clinical isolates associated with colonization and with
      systemic and hematogenous candidiasis. Among 347 C. glabrata isolates, the
      overall rates of resistance to fluconazole (MIC > or = 64 micro g/ml) and
      itraconazole (MIC > or = 1 micro g/ml) were 10.7 and 15.2%, respectively,
      although for half (n = 148) of the itraconazole-susceptible isolates the MICs
      (0.25 to 0.5 micro g/ml) were in the susceptible-dependent upon dose range.
      Fluconazole resistance was more common among C. glabrata isolates obtained from
      centers caring for patients with cancer (MICs at which 90% of isolates are
      inhibited [MIC(90)s] = 32 micro g/ml) or AIDS (MIC(90)s > 64 micro g/ml) than
      among C. glabrata isolates from a community-based university medical center
      (MIC(90)s = 16 micro g/ml) (P = 0.001). Thirty-three bloodstream isolates and
      those obtained from other body sites had similar in vitro susceptibility
      profiles. The fluconazole MIC(90)s (< or =16 micro g/ml) for C. glabrata yeast
      isolates from the gastrointestinal tract were lower than those (> or =64 micro
      g/ml) for C. glabrata isolates from respiratory and urinary tract samples (P =
      0.01). A similar discrepancy for itraconazole was not significant (P > 0.5). We
      did not observe differences in fluconazole or itraconazole susceptibility
      profiles among C. glabrata isolates associated with either hematogenous
      dissemination or colonization. The significant discrepancy in antifungal
      susceptibility among C. glabrata organisms isolated from hospitals in the same
      geographic region emphasizes the significance of periodic susceptibility
      surveillance programs for individual institutions, especially those providing
      care to patients at risk.

PMID- 12234858
TI  - In vitro activity of the new oxazolidinone AZD2563 against Enterococci.
AB  - The activity of a new oxazolidinone antimicrobial, AZD2563, was assessed against
      >500 clinical isolates of enterococci representing six species. All isolates,
      including those resistant to other antibiotic classes, were inhibited by AZD2563
      at concentrations </=2 micro g/ml, except for four strains resistant to
      linezolid. In most cases, AZD2563 was twofold more active than linezolid against
      enterococci.

PMID- 12234859
TI  - In vitro activities of newer quinolones against bacteroides group organisms.
AB  - The activities of BMS-284576, clinafloxacin, moxifloxacin, sitafloxacin,
      trovafloxacin, imipenem, cefoxitin, and clindamycin against 589 Bacteroides
      fragilis group isolates were determined. The activity of BMS-284576 was
      comparable to that of trovafloxacin. Sitafloxacin and clinafloxacin were the most
      active quinolones, and moxifloxacin was the least active. B. fragilis was the
      most susceptible of the species, and Bacteroides vulgatus was the most resistant.
      Association of specific antibiotic resistance with Bacteroides species was noted
      for all quinolones.

PMID- 12234860
TI  - Use of fluoroquinolones in patients with chronic hepatitis C virus-induced liver
      failure.
AB  - Fluroquinolone antibiotics have been reported to have antiviral properties
      against RNA viruses, including hepatitis C virus (HCV). In the present study,
      five patients with advanced liver disease secondary to chronic HCV received 500
      mg daily of oral ciprofloxacin for 30 days. Serum HCV-RNA levels and liver enzyme
      abnormalities remained largely unchanged. Thus, the role of fluoroquinolones as
      antiviral agents for chronic HCV in patients with advanced liver disease appears
      to be limited.

PMID- 12234861
TI  - Comparison of in vitro activities of gatifloxacin and ciprofloxacin against four
      taxa of rapidly growing mycobacteria.
AB  - By using current NCCLS broth microdilution methods, we found that gatifloxacin
      inhibited 90% of the isolates of the Mycobacterium fortuitum group at < or =0.12
      micro g/ml and 90% of the Mycobacterium chelonae isolates at < or =4 micro g/ml.
      Gatifloxacin was generally fourfold more active than ciprofloxacin. We recommend
      that both gatifloxacin and ciprofloxacin be tested routinely against rapidly
      growing mycobacteria.

PMID- 12234862
TI  - Carbapenem-resistant Pseudomonas aeruginosa in malaysia producing IMP-7 beta
      lactamase.
AB  - We have isolated and identified a carbapenem-resistant Pseudomonas aeruginosa
      strain from Malaysia that produces an IMP-7 metallo-beta-lactamase. This isolate
      showed high-level resistance to meropenem and imipenem, the MICs of which were
      256 and 128 micro g/ml, respectively. Isoelectric focusing analyses revealed pI
      values of >9.0, 8.2, and 7.8, which indicated the possible presence of IMP and
      OXA. DNA sequencing confirmed the identity of the IMP-7 determinant.

PMID- 12234863
TI  - Efficacy of linezolid against methicillin-resistant or vancomycin-insensitive
      Staphylococcus aureus in a model of hematogenous pulmonary infection.
AB  - We investigated the activities of linezolid, vancomycin, and teicoplanin in a
      murine model of hematogenous pulmonary infection with Staphylococcus aureus. Our
      results demonstrate that linezolid clearly reduced bacterial numbers in the
      methicillin-resistant S. aureus hematogenous infection model and significantly
      improved the survival rate of immunocompromised mice infected with vancomycin
      insensitive S. aureus compared with vancomycin and teicoplanin. The
      pharmacokinetic profiles also reflected the effectiveness of linezolid.

PMID- 12234864
TI  - Inhibition of human immunodeficiency virus type 1 integration by diketo
      derivatives.
AB  - A series of diketo derivatives was found to inhibit human immunodeficiency virus
      type 1 (HIV-1) integrase activity. Only L-708,906 inhibited the replication of
      HIV-1(III(B)) (50% effective concentration, 12 micro M), HIV-1 clinical strains,
      HIV-1 strains resistant to reverse transcriptase or fusion inhibitors, HIV-2 (ROD
      strain) and simian immunodeficiency virus (MAC(251)). The combinations of L
      708,906 with zidovudine, nevirapine, or nelfinavir proved to be subsynergistic.
      In cell culture, addition of L-708,906 could be postponed for 7 h after
      infection, a moment coinciding with HIV integration. Inhibition of integration in
      cell culture was confirmed by quantitative Alu-PCR.

PMID- 12234865
TI  - In vitro activities of investigational triazoles against Fusarium species:
      effects of inoculum size and incubation time on broth microdilution
      susceptibility test results.
AB  - We studied the effects of inoculum size and incubation time on the susceptibility
      testing results for various antifungal agents against 22 Fusarium isolates by the
      NCCLS microdilution method. Increased inoculum size and extended incubation time
      resulted in elevated MICs. Posaconazole and voriconazole exhibited promising
      antifungal activities.

PMID- 12234866
TI  - Inhibition of human immunodeficiency virus type 1 isolates by the integrase
      inhibitor L-731,988, a diketo Acid.
AB  - L-731,988 inhibits human immunodeficiency virus (HIV) replication through
      integrase. In this study, approximately 600 nM L-731,988 inhibited the
      replication of 12 HIV type 1 isolates from multiple clades, including primary
      isolates and cloned viruses. These data suggest that diketo acids or their
      derivatives may prove useful on a worldwide basis in treating HIV infection.

PMID- 12234867
TI  - Simple method for assaying colistin methanesulfonate in plasma and urine using
      high-performance liquid chromatography.
AB  - A simple and sensitive high-performance liquid chromatographic method is
      described for the determination of colistimethate sodium in plasma and urine. The
      accuracy and reproducibility was within 10.1 and 11.2% with rat plasma and urine,
      respectively. Several commonly coadministered antibacterial agents do not
      interfere with the assay.

PMID- 12234868
TI  - Antimicrobial properties of milk: dependence on presence of xanthine oxidase and
      nitrite.
AB  - Human and bovine milk inhibited the metabolic activity of Escherichia coli, as
      shown by luminescence monitoring of constructs expressing the luxCDABE genes.
      Inhibition was dependent on both xanthine oxidase (XO) activity and on the
      presence of nitrite, implying that XO-generated nitric oxide functions as an
      antibacterial agent.

PMID- 12234869
TI  - Fluoroquinolone-resistant Streptococcus pneumoniae strains occur frequently in
      elderly patients in Japan.
AB  - We identified and genetically characterized seven fluoroquinolone-resistant
      Streptococcus pneumoniae strains among 293 clinical strains isolated from 1999 to
      2001 in Japan. The resistant strains were isolated only from adults, and 7 of 31
      isolates (22.6%) were from patients more than 20 years old. Resistant strains
      were not found in 262 isolates from children under age 10.

PMID- 12234871
TI  - Effects of the Des-F(6)-quinolone garenoxacin (BMS-284756), in comparison to
      those of ciprofloxacin and ofloxacin, on joint cartilage in immature rats.
AB  - We did not observe signs of chondrotoxicity in immature rats treated orally with
      garenoxacin (BMS-284756) at doses up to five times 600 mg/kg of body weight or
      with ciprofloxacin, whereas ofloxacin induced typical cartilage lesions. The peak
      plasma garenoxacin concentration was 25.5 mg/liter after administration of a dose
      of 600 mg/kg once daily for 5 days. Assuming that this model is predictive of
      human risk, BMS-284756 and ciprofloxacin should be more suitable for pediatric
      use than ofloxacin.

PMID- 12234870
TI  - Inducible AmpC beta-lactamase of a new member Enterobacteriaceae.
AB  - Extensive biochemical testing and 16S rRNA and rpoB sequence analysis revealed
      that clinical strain CF01Ent1, initially identified as Buttiauxella agrestis by
      the use of Api 32 biochemical strips, is a new organism in the Enterobacteriaceae
      family. It produced an inducible AmpC-type beta-lactamase whose sequence shares
      69 to 72% identity with those of the other AmpC-type beta-lactamases of
      ENTEROBACTERIACEAE: This enzyme exhibits an atypical high affinity for all beta
      lactams tested.

PMID- 12234872
TI  - In vitro synergistic interaction between amphotericin B and pentamidine against
      Scedosporium prolificans.
AB  - To develop new approaches for the treatment of invasive infections caused by
      Scedosporium prolificans, the in vitro interaction between amphotericin B and
      pentamidine against 30 clinical isolates was evaluated using a checkerboard
      microdilution method based on the National Committee for Clinical Laboratory
      Standards M38-P guidelines. The interaction between the drugs was analyzed using
      fractional inhibitory concentration index (FICI) analysis and response surface
      modeling. Amphotericin B alone was inactive against all the isolates. The
      geometric mean MIC for pentamidine was 57 micro g/ml (range, 8 to 256 micro g/ml;
      MIC at which 50% of the isolates tested were inhibited [MIC(50)], 64 micro g/ml;
      MIC(90), 128 micro g/ml). The combination was synergistic against 28 of 30
      isolates (93.3%) by FICI analysis and 30 of 30 (100%) by response surface
      modeling analysis. Antagonism was not observed.

PMID- 12234873
TI  - Inhibition of secretion of interleukin-1alpha and tumor necrosis factor alpha by
      the ketolide antibiotic telithromycin.
AB  - The antibiotic telithromycin was examined for its effect on secretion of
      interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, IL-10, and tumor necrosis factor
      alpha (TNF-alpha) by lipopolysaccharide (LPS)-stimulated monocytes of eight human
      donors. Secretion of each cytokine was significantly increased by LPS alone,
      whereas treatment with telithromycin significantly inhibited secretion of IL
      1alpha and TNF-alpha but not secretion of IL-1beta, IL-6, and IL-10.
      Telithromycin had immunomodulatory effects as a result of alteration of secretion
      of IL-1alpha and TNF-alpha by monocytes.

PMID- 12234874
TI  - Effects of clarithromycin and amoxicillin on gastric emptying in rats.
AB  - The effects of oral administration of clarithromycin (CLR), amoxicillin (AMX),
      and lansoprazole (LPZ) on gastric emptying in rats were investigated by a glass
      powder method and a phenol red method. By both test methods, no significant
      effects on gastric emptying were observed when CLR, AMX, or LPZ was administered
      alone or when the three drugs were administered concomitantly. The levels of
      gastrointestinal absorption of [(14)C]CLR and [(14)C]AMX were measured. Four
      hours after injection of [(14)C]CLR or [(14)C]AMX into the stomach and duodenum
      loops of rats, 86.63 and 1.27% of the original amount of [(14)C]CLR administered
      were recovered in the contents of the stomach and duodenum loops, respectively,
      and 80.01 and 55.88% of the original amount of [(14)C]AMX administered were
      recovered in the contents of the stomach and duodenum loops, respectively.

PMID- 12234875
TI  - Gene dosage and linezolid resistance in Enterococcus faecium and Enterococcus
      faecalis.
AB  - Resistance to linezolid has been associated with a G2576U mutation in domain V of
      the 23S rRNA. We analyzed nine clinical isolates of linezolid-resistant
      enterococci and showed a clear association between the number of 23S rRNA genes
      containing this mutation and the level of linezolid resistance expressed.

PMID- 12234876
TI  - Contribution of the C-8-methoxy group of gatifloxacin to inhibition of type II
      topoisomerases of Staphylococcus aureus.

PMID- 12234878
TI  - Retinopathy of prematurity.

PMID- 12234879
TI  - What do you do about ROP screening in "big" babies?

PMID- 12234880
TI  - How double eyelashes give you swollen legs.

PMID- 12234881
TI  - Ocular disease in patients with tuberculosis and HIV presenting with fever in
      Africa.
AB  - AIMS: To investigate ocular disease in patients with tuberculosis (TB) and HIV in
      Africa presenting with fever, and to determine if indirect ophthalmoscopy is
      useful in the diagnosis of mycobacteraemia. METHODS: A prospective study of all
      adult patients admitted with fever to a large central hospital in Malawi, Africa.
      All recruited patients had an ophthalmic examination, HIV tests, chest x ray,
      sputum examinations, bacterial and mycobacterial blood cultures, and malaria
      slide to observe the presence of parasites. RESULTS: 307 patients were recruited;
      109 (36%) had TB, including 53 (17%) with mycobacteraemia; 255 (83%) had HIV and
      191 (62%) had AIDS. Of the patients with TB 102 (94%) had HIV. Choroidal
      granulomas were found in four patients, all of whom had AIDS; three (2.8% of
      those with TB) had disseminated TB with mycobacteraemia, and one had persistent
      fever but no other evidence of TB. Among the patients with AIDS, 32 (17%) had
      microangiopathy manifest by cotton wool spots; one (0.5%) had signs of active
      cytomegalovirus (CMV) retinitis. The presence of microangiopathy was not related
      to TB. CONCLUSIONS: In Malawian patients with TB presenting acutely with fever,
      choroidal granulomas were found in 2.8%, and were concurrent with mycobacteraemia
      and AIDS. Ophthalmoscopy was not a useful aid in the diagnosis of
      mycobacteraemia. Cytomegalovirus (CMV) retinitis is rarely seen in African AIDS
      patients. This may be the result of mortality early in the disease course, or
      differences in race, HIV subtype, or comorbidity.

PMID- 12234882
TI  - Knowledge about cataract, glaucoma, and age related macular degeneration in the
      Hong Kong Chinese population.
AB  - AIMS: Patients' knowledge and participation in their care are important in
      prevention of blindness from common eye diseases such as cataract, glaucoma, and
      age related macular degeneration (AMD). The aim of this study was to measure
      knowledge of these conditions in the Hong Kong Chinese population. METHODS:
      Subjects aged 40 and above in the Shatin district of Hong Kong were randomly
      selected as part of a larger study of causes of adult visual loss. The subjects
      received eye examinations in which the primary cause of visual disability was
      recorded. The respondents were asked by trained interviewers in a standardised
      fashion about their knowledge of cataract, glaucoma, and AMD. Their answers were
      rated for accuracy by a senior ophthalmologist. RESULTS: Out of the 2538 eyes
      examined, 7.0% had visual acuity less than 6/18. Fully 69.6% of the visual
      disability for those aged 60 or above was caused by cataract, AMD, or glaucoma.
      Awareness of cataract in particular was high, in that over 90% of respondents had
      heard of it. However, only 22.9% of them could describe cataract symptoms
      correctly, and these percentages were even lower in glaucoma (10.2%) and AMD
      (<1%). Over 40% of subjects did not know that surgery was an appropriate
      treatment for cataract. CONCLUSION: This sample of the Hong Kong Chinese
      population had limited knowledge of common eye diseases. Educational programmes
      to enhance public awareness may be needed to improve the effectiveness of health
      promotion and thus prevent unnecessary blindness.

PMID- 12234883
TI  - Incidence of iris colour change in latanoprost treated eyes.
AB  - AIMS: To determine the incidence of increased iris pigmentation in eyes treated
      with chronic latanoprost. This is an observational, cohort study. METHODS: The
      anterior segments of both eyes of 43 patients with glaucoma were photographed
      after unilateral latanoprost therapy. Two independent, masked observers analysed
      the slides of both eyes of the study participants, and compared the iris
      pigmentation of both eyes of each patient using a stereo viewer. RESULTS: 30
      patients (69.7%) had a definite acquired iridial anisochromia; 15 patients (50%)
      had increased superficial iris pigmentation with a "granular" appearance (type 1
      change), and 15 patients (50%) had an increased "stromal pigmentation"-that is,
      the affected iris appeared darker than the fellow eye, but without a "granular"
      appearance (type 2 change). CONCLUSION: The incidence of increased iris
      pigmentation induced by latanoprost is much higher than previously reported. The
      high prevalence of mixed iris colour found in this population and the fact that
      the patients studied were undergoing unilateral therapy may explain these
      results.

PMID- 12234884
TI  - Pulsatile ocular blood flow: the effect of the Valsalva manoeuvre in open angle
      and normal tension glaucoma: a case report and prospective study.
AB  - AIM: A case of severe normal tension glaucoma is reported in a trumpet player,
      along with a study investigating the association between glaucoma and raised
      intrathoracic pressure, using measurements of pulsatile ocular blood flow (POBF).
      METHODS: Three patient groups were studied; normals (n = 34), untreated primary
      open angle glaucoma (POAG) (n = 20), and untreated normal tension glaucoma (NTG)
      (n = 22), with a total of 76 patients who underwent measurements of POBF using
      the OBF pneumotonometer at rest and while forcibly exhaling through a mouthpiece
      connected to a mercury manometer (30 mm Hg) (Valsalva manoeuvre). RESULTS: POBF
      fell during Valsalva in all groups with the greatest predictor being the resting
      value of POBF. There was no evidence of significant differences in the mean
      change in POBF occurring during the Valsalva manoeuvre for the three groups
      studied before or after adjusting for the sex, the resting POBF, and the resting
      IOP of the patients (p = 0.294 and p = 0.542, respectively). However,
      statistically significant associations were found between the change in POBF and
      sex (p = 0.049), resting POBF (p<0.0001) and resting IOP (p = 0.032). Males had a
      greater drop, on average, in POBF during Valsalva manoeuvre than females after
      adjusting for the other factors. Additionally, there was a significant difference
      in the mean change in IOP during Valsalva for the three groups (p = 0.002), with
      the difference occurring between the normal and POAG groups (p<0.005). The POAG
      group had, on average, a drop in IOP during Valsalva, while the other two groups
      had an increase in IOP. Also noted was a significant difference in the
      distributions of the risk factors among the three groups (p = 0.002).
      CONCLUSIONS: This study demonstrates no difference between groups with respect to
      resting or Valsalva POBF, but does demonstrate a possible trend with respect to
      IOP, with a drop in IOP occurring during Valsalva in the POAG group. There is,
      however, much variability in the data left unexplained by our models. Thus,
      unfortunately, we cannot advise our trumpet player whether his NTG is directly
      related to his trumpet playing.

PMID- 12234885
TI  - Clinicopathological correlation of polypoidal choroidal vasculopathy revealed by
      ultrastructural study.
AB  - AIMS: To describe the clinical and histopathological findings in a patient with
      polypoidal choroidal vasculopathy. METHODS: A 76 year old Japanese man had a
      discrete, orange-red lesion of 1 disc diameter in the macula, with the
      fluorescein and indocyanine green angiographic and optical coherence tomographic
      findings compatible with polypoidal choroidal vasculopathy. He underwent a
      surgical removal of the macular lesion, followed by light and electron
      microscopic examinations. RESULTS: The histopathological examination revealed
      that the specimen consisted of degenerated retinal pigment epithelium-Bruch's
      membrane-choriocapillaris complex and inner choroid. A tortuous, unusually
      dilated venule was present adjacent to an arteriole with marked sclerotic
      changes, appearing to form arteriovenous crossing. These vessels seemed to
      represent native inner choroidal vessels, and had haemorrhage per diapedesis.
      Blood cells and fibrin filled the lumina of the vessels and accumulated in the
      extravascular spaces, indicating vascular stasis. CONCLUSION: Hyperpermeability
      and haemorrhage due to stasis of a dilated venule and an arteriole involved by
      sclerosis at the site where they cross in the inner choroid might cause oedema
      and degeneration of the tissue. Voluminous accumulation of blood cells and fibrin
      might generate elevation of tissue pressure sufficient to displace the weakened
      lesion anteriorly. The result suggests that the polypoidal vessels in this case
      represent abnormality in the inner choroidal vasculature.

PMID- 12234886
TI  - Autofluorescence imaging after selective RPE laser treatment in macular diseases
      and clinical outcome: a pilot study.
AB  - AIM: Selective retinal pigment epithelium (RPE) laser treatment is a new
      technique which selectively damages the RPE while sparing the neural retina. One
      difficulty is the inability to visualise the laser lesions. The aim of the study
      was to investigate whether fundus autofluorescence (AF) is changed because of the
      RPE damage, and thus might be used for treatment control. Additionally, the
      clinical course of patients with various macular diseases was evaluated. METHODS:
      26 patients with macular diseases (diabetic maculopathy (DMP), soft drusen
      maculopathy (AMD), and central serous retinopathy (CSR)) were treated and
      followed up for at least 6 months. Treatment was performed with a train of
      repetitive short laser pulses (800 ns) of a frequency doubled Nd:YAG laser
      (parameters: 532 nm, 50 and 500 pulses at 100 and 500 Hz, retinal spot diameter
      200 micro m, pulse energies 75-175 micro J). AF was excited by 488 nm and
      detected by a barrier filter at 500 nm (HRA, Heidelberg Engineering, Germany).
      Patients were examined by ophthalmoscopy, fluorescein angiography, and
      autofluorescence measurements at various times after treatment (10 minutes, 1
      hour, 1 and 6 weeks, 3, 6, and 12 months). RESULTS: Fluorescein angiography
      showed leakage from the irradiated areas for about 1 week after treatment. None
      of the laser lesions was ophthalmoscopically visible during treatment.
      Identification of the lesions was possible by AF imaging showing an intensity
      decay in the irradiated area in 22 out of 26 patients, predominantly in patients
      with CSR and AMD. Lesions could be identified 10 minutes after treatment as
      hypoautofluorescent spots, which were more pronounced 1 hour later. During follow
      up the laser spots became hyperautofluorescent. In patients with DMP some AF
      images were less helpful because of diffuse oedema and larger retinal thickness.
      In these cases ICG angiography was able to confirm therapeutic success very well.
      Most of the patients have had benefit from the treatment, with best results
      obtained for CSR patients. CONCLUSION: Imaging of non-visible selective RPE laser
      effects can be achieved by AF measurements predominantly in patients without
      retinal oedema. Therefore, AF may replace invasive fluorescein angiography in
      many cases to verify therapeutic laser success. Selective laser treatment has the
      potential to improve the prognosis of macular diseases without the risk of laser
      scotomas.

PMID- 12234887
TI  - Entonox as an analgesic agent during panretinal photocoagulation.
AB  - BACKGROUND/AIMS: Panretinal photocoagulation (PRP) reduces the risk of visual
      loss in proliferative diabetic retinopathy but some patients cannot tolerate PRP
      because of pain. Inhaled Entonox was evaluated as an analgesic during PRP.
      METHODS: A randomised, crossover, double masked pilot study was performed.
      Patients inhaled either air or Entonox and half the PRP was applied. The
      treatment was completed with the alternate inhaled gas. Patients graded pain
      experienced during both stages of the treatment using a visual analogue scale.
      Pain scores were compared using a paired t test. RESULTS: 20 patients
      participated. Mean pain scores from the Entonox and air treatments were 2.94 (SD
      2.73) versus 3.73 (SD 3.20) respectively (p<0.03). CONCLUSION: Entonox can be
      used as a safe and effective analgesic agent during PRP treatment.

PMID- 12234888
TI  - Measurement of optic nerve sheath diameter by ultrasound: a means of detecting
      acute raised intracranial pressure in hydrocephalus.
AB  - AIM: To evaluate the utility of measuring the optic nerve sheath diameter in
      children with shunted hydrocephalus, suspected of having raised intracranial
      pressure. METHODS: 23 children with shunted hydrocephalus were examined, six had
      well controlled ICP, 17 however manifested symptoms suggestive of intracranial
      hypertension. A clinical history was taken from all patients and their parents or
      carers. The shunt valve was examined clinically, and signs of raised intracranial
      pressure were sought. Ultrasound examination was performed in both eyes to
      measure the optic nerve sheath diameters 3 mm behind the globe. These
      measurements were compared with control data obtained from 102 children who
      attended the radiology department for unrelated renal ultrasound examination.
      RESULTS: Control data suggested that the upper limit of normal for optic nerve
      sheath diameter is 4.5 mm (measured 3 mm behind the globe) in patients over 1
      year of age, and 4.0 mm in children less than 1 year of age. Those patients with
      functioning ventriculoperitoneal shunts had a mean optic nerve sheath diameter of
      2.9 (SD 0.5) mm; those with raised intracranial pressure had a mean optic nerve
      sheath diameter of 5.6 (0.6) mm (p<0.0001). These results confirm that optic
      nerve sheath diameters in excess of the control data are strongly suggestive of
      raised intracranial pressure. CONCLUSION: The evaluation of the optic nerve
      sheath diameter is a simple non-invasive procedure, which is a potentially useful
      tool in the assessment and monitoring of children with hydrocephalus suspected of
      having raised intracranial pressure.

PMID- 12234889
TI  - Lyophilisates for drug delivery in ophthalmology: pharmacokinetics of fluorescein
      in the human anterior segment.
AB  - AIMS: To assess the ocular bioavailability of fluorescein from a novel water
      free, freeze dried ophthalmic drug delivery system compared to conventional
      preservative-free fluorescein eye drops. METHODS: Sodium fluorescein 0.17% was
      dissolved in an aqueous solution of hydroxypropylmethyl cellulose 1.0% (HPMC),
      deposited on sterilised flexible hydrophobic poly(tetrafluoroethylene) (PTFE)
      carrier strips and freeze dried under aseptic conditions. The fluorescein dose of
      the lyophilisate was 68 micro g, corresponding to a single conventional drop of
      40 micro l fluorescein 0.17% solution. In a randomised, open label study 12
      healthy volunteers applied the lyophilised fluorescein to one eye and one drop of
      conventional fluorescein ophthalmic solution to the fellow eye. Fluorophotometry
      measurements of fluorescein concentrations in the anterior segment were performed
      with the Fluorotron Master II (Ocumetrics, USA) before and +15, 30, 45, 60, 120,
      and 180 minutes after application. RESULTS: At all times anterior chamber
      fluorescein concentration was greater in the lyophysilate treated eye than the
      solution treated eye. The magnitude of this difference ranged from 2-5.3 times
      and was statistically significant. CONCLUSION: The greater intraocular
      bioavailability of fluorescein from the lyophilisate relative to the solution
      suggests that it may be a useful method for delivering substances to the eye.

PMID- 12234890
TI  - Vision impairment and older drivers: who's driving?
AB  - AIM: To establish the association between impaired vision and drivers' decisions
      to stop driving, voluntarily restrict driving, and motor vehicle accidents.
      METHODS: Driving related questions were included in a population based study that
      determined the prevalence and incidence of eye disease. Stratified random cluster
      samples based on census collector districts were selected from the Melbourne
      Statistical Division. Eligible participants aged 44 years and over were
      interviewed and underwent a comprehensive ophthalmic examination. The outcomes of
      interest were the decision to stop driving, limiting driving in specified
      conditions, and driving accidents. The associations between these outcomes and
      the legally prescribed visual acuity (<6/12) for a driver's licence were
      investigated. RESULTS: The mean age of the 2594/3040 (85%) eligible participants
      was 62.5 (range 44-101). People with visual acuity less than 6/12 were no more
      likely to have an accident than those with better vision (chi(2) = 0.175, p>0.9).
      Older drivers with impaired vision, more so than younger adults, restrict their
      driving in visually demanding situations (p<0.05). Of the current drivers, 2.6%
      have vision less than that required to obtain a driver's licence. The risk of
      having an accident increased with distance driven (OR 2.57, CL 1.63, 4.04 for
      distance >31 000 km) but not with age. CONCLUSION: There was no greater
      likelihood of self reported driving accidents for drivers with impaired vision
      than those with good vision. While many older drivers with impaired vision limit
      their driving in adverse conditions and some drivers with impaired vision stop
      driving, there are a significant number of current drivers with impaired vision.

PMID- 12234892
TI  - Screening for retinopathy of prematurity.
AB  - AIM: A cross sectional (prevalence) study was performed to assess the usefulness
      and sensitivity of commonly employed criteria to identify infants for routine
      ophthalmoscopic screening for retinopathy of prematurity (ROP). METHODS: At a
      tertiary care centre between 1 January 1992 and 30 June 1998, experienced
      vitreoretinal specialists screened 438 premature infants for ROP. Retinal
      maturity and the presence of ROP were determined by indirect ophthalmoscopic
      examinations. RESULTS: Of the eligible infants surviving 28 days, 276 (91.7%) of
      301 infants with birth weights </=1500 g and 162 (52.3%) of 310 infants with
      birth weights between 1501 and 2500 g were screened for ROP. 10 (3.9%) of the 310
      infants with larger birth weights developed stage 1 or 2 ROP. Two (0.6%) of the
      310 infants with larger birth weights developed stage 3 ROP. These two infants
      progressed to threshold ROP and required treatment. CONCLUSIONS: Relatively
      restrictive criteria to identify premature infants eligible for routine
      ophthalmoscopic screening for ROP may be the cause for some infants going
      unexamined and their ROP undetected.

PMID- 12234891
TI  - Incidence of ROP in two consecutive Swedish population based studies.
AB  - AIMS: To prospectively analyse the present incidence of ROP (retinopathy of
      prematurity) in a well defined geographical area in Sweden, and to compare it
      with that from a decade earlier in exactly the same area. METHODS: Infants born
      between 1 August 1998 and 31 July 2000 with a birth weight of 1500 g or less were
      studied. They were screened for ROP from 5 weeks of postnatal age until the
      retina was entirely vascularised. The incidence of ROP, with its various stages,
      was compared with that of a previous (1988-90) population based study in the same
      geographical area. RESULTS: The incidence of ROP in the present study was 36.4%
      (mild (18.2%) and severe ROP (18.2%)), which was similar to that of the previous
      study. Gestational age at birth remained the most important risk factor for ROP.
      We found a change in the distribution of ROP. The probability of ROP,
      particularly severe ROP, was highest in the most immature infants while it was
      lower in the least immature ones. CONCLUSIONS: The incidence of ROP remained the
      same in two consecutive population based studies. The more "mature" infants
      developed ROP, particularly severe ROP, less often, while the most immature
      infants had ROP more often, particularly severe ROP.

PMID- 12234893
TI  - Psychophysical characterisation of early functional loss in glaucoma and ocular
      hypertension.
AB  - AIM: The psychophysical evaluation of selective cell loss in early glaucoma and
      ocular hypertension. METHODS: Contrast sensitivity was measured for the detection
      of luminance modulated gratings at a range of spatial (0.5, 2, 8 c/deg) and
      temporal (0, 16 Hz) frequency combinations in three groups of age matched
      patients (primary open angle glaucoma, ocular hypertension, normal controls;
      n=16). Stimuli of 5 degrees were presented foveally and at 15 degrees along the
      nasal horizontal meridian under photopic conditions. RESULTS: Fovea: Compared to
      the normal group, the thresholds for the glaucoma patients were significantly
      elevated at all spatial and temporal frequencies (p<0.0001), but this reduction
      was not significantly different at any particular spatial or temporal frequency
      (p>0.1). There was no difference in contrast sensitivity between the normals and
      OHTs (p>0.10). Periphery: The thresholds of the glaucoma patients were elevated
      compared to the normal controls (p<0.01). The loss of sensitivity was slightly
      greater at the higher spatial frequencies for both stationary and flickering
      patterns but this did not reach significance (p=0.09). The contrast sensitivity
      in normal and OHT groups was not significantly different (p>0.10). CONCLUSIONS:
      In early glaucoma, the reduction in contrast sensitivity to stimuli which isolate
      the magnocellular pathway (0.5 c/deg, 16 Hz) was not significantly different
      compared with the reduction in contrast sensitivity to stimuli that isolate the
      parvocellular pathway. These findings are not consistent with the hypothesis that
      the magnocellular pathway is selectively damaged in early glaucoma.

PMID- 12234894
TI  - Three dimensional ultrasound of retinoblastoma: initial experience.
AB  - AIM: To use 3D ultrasonography (3DUS) for the diagnosis of retinoblastoma.
      METHODS: Five eyes of three children with retinoblastoma were evaluated using a
      commercially available computerised 3DUS system. Interactive sectioning of the
      stored and reconstructed 3D volumes were performed. 3DUS and histopathological
      findings were correlated after enucleation. RESULTS: 3DUS examination revealed
      characteristics consistent with retinoblastoma: endophytic mass, retinal
      detachment, intratumoural calcifications, and secondary orbital shadowing. Unlike
      2D imaging, 3DUS allowed for analysis of the acquired and stored volumes.
      Rotation and sectioning of this volume allowed the discovery of new oblique and
      coronal views. For example, calcium related orbital shadows were seen as 3D
      volumes and (coronal) cross sections of the optic nerve were evaluated for
      evidence of intraneural invasion by retinoblastoma. CONCLUSION: This is the first
      reported series of patients examined with 3DUS imaging for retinoblastoma. This
      technique allowed for new oblique and coronal views of the tumour and optic
      nerve. The ability to retrospectively analyse the (scanned and stored) ocular
      volume facilitated patient care, teaching, tumour-volume analysis, and
      telemedicine.

PMID- 12234895
TI  - Diabetic macular oedema: the effect of photocoagulation on fluorescein transport
      across the blood-retinal barrier.
AB  - BACKGROUND/AIM: The visual loss secondary to diabetic macular oedema can be
      controlled to some extent by photocoagulation, though the mechanism of action is
      largely unknown. The purpose of the present study was to quantitate the effect of
      photocoagulation on the blood-retinal barrier using fluorescein as a tracer of
      passive and active transport. METHODS: A prospective study of 46 eyes in 34
      patients with clinically significant macular oedema (CSMO) examined by vitreous
      fluorometry before and 6 months after macular photocoagulation treatment.
      RESULTS: In 23 eyes CSMO was not present at follow up (responding eyes), in
      another 23 other eyes CSMO was still present (non-responding eyes). With
      reference to the presence or absence of CSMO at follow up, the passive transport
      (permeability) for responding eyes decreased after photocoagulation in contrast
      with an increase in non-responding eyes; the difference between the groups at
      follow up was significant (p=0.03). The active transport for responding eyes
      decreased slightly at follow up, while it increased for non-responding eyes; the
      difference between the groups at follow up was not significant (p=0.09).
      CONCLUSION: Following photocoagulation a reduction of diabetic macular oedema,
      defined as disappearance of CSMO, is paralleled by a decrease of the passive
      permeability while the hypothesis of an increase in the active transport from the
      retina to the blood could not be supported by this study.

PMID- 12234896
TI  - Effect of inhalation of different mixtures of O(2) and CO(2) on retinal blood
      flow.
AB  - AIM: To determine the effects of various mixtures of O(2) and CO(2) on retinal
      blood flow in healthy subjects. METHODS: A randomised, double masked, four way
      crossover trial was carried out in 12 healthy male non-smoking subjects. Gas
      mixtures (100% O(2), 97.5% O(2) + 2.5% CO(2), 95% O(2) + 5% CO(2), and 92% O(2) +
      8% CO(2)) were administered for 10 minutes each. Two non-invasive methods were
      used: laser Doppler velocimetry (LDV) for measurement of retinal blood velocity
      and fundus imaging with the Zeiss retinal vessel analyser (RVA) for the
      assessment of retinal vessel diameters. Arterial pH, pCO(2), and pO(2) were
      determined with an automatic blood gas analysis system. Retinal blood flow
      through a major temporal vein was calculated. RESULTS: Retinal blood velocity,
      retinal vessel diameter, and retinal blood flow decreased during all breathing
      periods (p <0.001 each). Administration of 92% O(2) + 8% CO(2) significantly
      increased SBP, MAP, and PR (p <0.001 each, versus baseline), whereas the other
      gas mixtures had little effect on systemic haemodynamics. Addition of 2.5%, 5%,
      and 8% CO(2) to oxygen caused a marked decrease in pH and an increase in pCO(2)
      (p <0.001 versus pure oxygen). CONCLUSIONS: Breathing of pure oxygen and oxygen
      in combination with carbon dioxide significantly decreases retinal blood flow.
      Based on these data the authors speculate that hyperoxia induced vasoconstriction
      is not due to changes in intravascular pH and cannot be counteracted by an
      intravascular increase in pCO(2).

PMID- 12234897
TI  - Long term visual outcome in amblyopia treatment.
AB  - AIM: To evaluate long term visual outcome of treatment for amblyopia. METHODS: In
      a previous study, 44 children with unilateral amblyopia caused by strabismus or
      anisometropia were enrolled in a prospective study investigating the results of
      treatment. All children were regularly examined up to at least 8 years of age and
      outcome was evaluated. All subjects were invited to a re-examination and in total
      26 subjects attended. Two of these were excluded because of insufficient records.
      The final sample consists of 24 subjects. Mean follow up time was 10.4 (SD 1.9)
      years. RESULTS: For the amblyopic eyes, 17% deteriorated in visual acuity, 50%
      were stable, and 33% gained in visual acuity. For the non-amblyopic eyes, 8% lost
      one line in visual acuity, 38% were stable, and 54% gained in visual acuity. No
      eye in any subject shifted more than 0.2 logMAR units. The increase in visual
      acuity for the non-amblyopic eyes was significant, while the increase for the
      amblyopic eyes was not. All straight eyed anisometropic amblyopes showed a
      distinct decrease in magnitude of anisometropia. CONCLUSIONS: Visual acuity was
      essentially stable in the amblyopic eyes 10 years after cessation of treatment in
      the studied population.

PMID- 12234898
TI  - Motor and sensory characteristics of infantile nystagmus.
AB  - BACKGROUND/AIMS: Past studies have explored some of the associations between
      particular motor and sensory characteristics and specific categories of non
      neurological infantile nystagmus. The purpose of this case study is to extend
      this body of work significantly by describing the trends and associations found
      in a database of 224 subjects who have undergone extensive clinical and
      psychophysical evaluations. METHODS: The records of 224 subjects with infantile
      nystagmus were examined, where 62% were idiopaths, 28% albinos, and 10% exhibited
      ocular anomalies. Recorded variables included age, mode of inheritance, birth
      history, nystagmus presentation, direction of the nystagmus, waveform types,
      spatial and temporal null zones, head postures and nodding, convergence,
      foveation, ocular alignment, refractive error, visual acuity, stereoacuity, and
      oscillopsia. RESULTS: The age distribution of the 224 patients was between 1
      month and 71 years, with the mean age and mode being 23 (SD 16) years and 16-20
      years respectively. By far the most common pattern of inheritance was found to be
      autosomal dominant (n = 40), with the nystagmus being observed by the age of 6
      months in 87% of the sample (n = 128). 139 (62%) of the 224 subjects were
      classified as idiopaths, 63 (28%) as albinos, and 22 (10%) exhibited ocular
      anomalies. Conjugate uniplanar horizontal oscillations were found in 174 (77.7%)
      of the sample. 32 (14.3%) had a torsional component to their nystagmus. 182
      (81.2%) were classed as congenital nystagmus (CN), 32 (14.3%) as manifest latent
      nystagmus (MLN), and 10 (4.5%) as a CN/MLN hybrid. Neither CN nor MLN waveforms
      were related to any of the three subject groups (idiopaths, albinos, and ocular
      anomalies) MLN was found in idiopaths and albinos, but most frequently in the
      ocular anomaly group. The most common oscillation was a horizontal jerk with
      extended foveation (n = 49; 27%). The amplitudes and frequencies of the nystagmus
      ranged between 0.3-15.7 degrees and 0.5-8 Hz, respectively. Periodic alternating
      nystagmus is commonly found in albinos. Albino subjects did not show a
      statistically significantly higher nystagmus intensity when compared with the
      idiopaths (p>0.01). 105 of 143 subjects (73%) had spatial nulls within plus or
      minus 10 degrees of the primary position although 98 subjects (69%) employed a
      compensatory head posture. Subjects with spatial null zones at or beyond plus or
      minus 20 degrees always adopted constant head postures. Head nodding was found in
      38 subjects (27% of the sample). Horizontal tropias were very common (133 out of
      213; 62.4%) and all but one of the 32 subjects with MLN exhibited a squint. Adult
      visual acuity is strongly related to the duration and accuracy of the foveation
      period. Visual acuity and stereoacuity were significantly better (p<0.01) in the
      idiopaths compared to the albino and ocular anomaly groups. 66 subjects out of a
      sample of 168 (39%) indicated that they had experienced oscillopsia at some time.
      CONCLUSIONS: There are strong ocular motor and sensory patterns and associations
      that can help define an infantile nystagmus. These include the nystagmus being
      bilateral, conjugate, horizontal uniplanar, and having an accelerating slow phase
      (that is, CN). Decelerating slow phases (that is, MLN) are frequently associated
      with strabismus and early form deprivation. Waveform shape (CN or MLN) is not
      pathognomonic of any of the three subject groups (idiopaths, albinos, or ocular
      anomalies). There is no one single stand alone ocular motor characteristic that
      can differentiate a benign form of infantile nystagmus (CN, MLN) from a
      neurological one. Rather, the clinician must consider a host of clinical
      features.

PMID- 12234899
TI  - Squamous cell carcinoma of the eyelids.
AB  - AIM: To review the clinical features, management, and outcomes of surgical
      treatment of eyelid squamous cell carcinoma (SCC). METHODS: A retrospective
      review of all eyelid SCCs treated between 1992 and 2001. RESULTS: 51 cases were
      identified in 50 patients. Patient ages ranged from 26 to 93 years, with a mean
      age of 65 years. 33 patients were male and 17 were female. The lesion was found
      on the lower lid in 31 cases, upper lid in five cases, lateral canthus in six
      cases, and medial canthus in nine cases. Perineural invasion was found in four
      patients, and orbital invasion in three patients. Recurrence occurred in one
      patient. Treatment was by complete excision with histological confirmation of
      clear margins. Exenteration was required in three patients. No patients developed
      lymph node or distant metastases. One patient, who declined treatment, died as a
      result of the tumour. Mean follow up was 31.1 months. CONCLUSIONS: Eyelid SCC is
      a relatively uncommon, but potentially fatal disease. However, if detected early
      and treated adequately, the prognosis is generally excellent. Treatment by
      complete excision with histological confirmation of tumour clearance is
      recommended. Perineural spread is an adverse prognostic sign, which may require
      postoperative radiotherapy. Orbital invasion is a rare complication but, if
      recognised early, can be treated effectively with exenteration. Because
      presentation varies and histological examination is required for accurate
      diagnosis, any suspicious lesion occurring on the eyelids should be excised or
      biopsied. All patients with eyelid SCC should be advised of the risk of recurrent
      or new tumours and encouraged to attend lifelong follow up. Prevention remains of
      prime importance in minimising the morbidity and mortality of these lesions.

PMID- 12234900
TI  - Exertion of the suppressive effects of IFN-gamma on experimental immune mediated
      blepharoconjunctivitis in Brown Norway rats during the induction phase but not
      the effector phase.
AB  - BACKGROUND/AIMS: Interferon gamma (IFN-gamma) knockout mice exhibit severe
      allergic conjunctivitis (AC), indicating that IFN-gamma regulates the development
      of AC. The authors examined whether this inhibitory effect of IFN-gamma is
      exerted during the induction or effector phase of experimental AC. METHODS:
      Experimental immune mediated blepharoconjunctivitis (EC) was induced in Brown
      Norway (BN) rats, using ovalbumin (OVA) as the antigen. To investigate the role
      of IFN-gamma in the induction phase, EC was induced by active immunisation and
      IFN-gamma (10 micro g/time, total 70 micro g), or phosphate buffered saline (PBS)
      as a control, was injected intraperitoneally every other day from the day of
      immunisation. The rats were challenged with OVA eye drops 13 days after
      immunisation, and 24 hours later, the eyes were harvested for histology. To
      examine the effects of IFN-gamma in the effector phase, OVA specific T cells were
      transferred into syngeneic rats and IFN-gamma (10 micro g/time, total 50 micro g)
      or PBS was injected each day after the transfer until induction of EC 4 days
      later with an OVA challenge. To investigate the role of endogenous IFN-gamma
      during the effector phase, an anti-IFN-gamma monoclonal antibody (3 mg/time) was
      injected on days 3 and 4. RESULTS: Injection of IFN-gamma into actively immunised
      rats suppressed eosinophilic infiltration but not infiltration of mononuclear
      cells. In contrast, neither IFN-gamma nor anti-IFN-gamma affected EC in passively
      immunised rats. CONCLUSION: IFN-gamma is a suppressive cytokine for the
      development of EC and exerts this suppressive effect during the induction phase.

PMID- 12234901
TI  - Inhibitory effect of losartan, an AT1 angiotensin II receptor antagonist, on
      increased leucocyte entrapment in retinal microcirculation of diabetic rats.
AB  - BACKGROUND: The effectiveness of losartan for the treatment of leucocyte
      entrapment in the retinal microcirculation of diabetic rats was evaluated
      quantitatively. METHODS: After diabetes was induced by injection of
      streptozotocin (STZ), the rats were divided into two subgroups. The first
      subgroup (n = 6), received no medications; the second subgroup (n = 6) was given
      fresh drinking water supplemented with losartan (5 mg/kg/day) for 4 weeks. Six
      rats that were not injected with STZ or given medications served as controls. 4
      weeks after intervention, leucocyte dynamics in the retina were observed using
      acridine orange digital fluorography. Leucocyte entrapment in the retina was
      compared among the three groups. RESULTS: In the untreated diabetic rats, the
      number of trapped leucocytes (6.1 (SD 1.4) cells/mm(2)) increased significantly
      compared with control rats (2.8 (1.2) cells/mm(2); p = 0.005) and diabetic rats
      treated with losartan (3.1 (0.9) cells/mm(2); p = 0.0002). CONCLUSIONS: Losartan,
      an AT1 angiotensin II receptor antagonist, inhibited increased leucocyte
      entrapment in the diabetic retina. The authors demonstrated that losartan may
      have therapeutic efficacy in preventing development of diabetic retinopathy.
      Further clinical studies of the effect of the angiotensin receptor antagonist on
      preventing development of diabetic retinopathy are needed.

PMID- 12234902
TI  - Expression of T lymphocyte chemoattractants and activation markers in vernal
      keratoconjunctivitis.
AB  - BACKGROUND/AIMS: T lymphocytes are present in increased numbers in the
      conjunctiva of patients with vernal keratoconjunctivitis (VKC) and their
      activation has a central role in the pathogenesis of the chronic allergic
      inflammatory reactions seen in VKC. The aims of this study were to examine the
      expression of three recently described potent T lymphocyte chemoattractants, PARC
      (pulmonary and activation regulated chemokine), macrophage derived chemokine
      (MDC), and I-309, the MDC receptor CCR4, and T lymphocyte activation markers,
      CD25, CD26, CD62L, CD71, and CD30, and to correlate them with the counts of
      CD3(+) T lymphocytes in the conjunctiva of patients with VKC. METHOD:
      Conjunctival biopsy specimens from 11 patients with active VKC, and eight control
      subjects were studied by immunohistochemical techniques using a panel of
      monoclonal and polyclonal antibodies directed against PARC, MDC, I-309, CCR4,
      CD25, CD26, CD62L, CD71, and CD30. The numbers of positively stained cells were
      counted. The phenotype of inflammatory cells expressing chemokines was examined
      by double immunohistochemistry. RESULTS: In the normal conjunctiva, vascular
      endothelial cells in the upper substantia propria showed weak immunoreactivity
      for CD26. There was no immunoreactivity for the other antibodies. VKC specimens
      showed inflammatory cells expressing PARC, MDC, and I-309. The numbers of PARC(+)
      inflammatory cells were higher than the numbers of MDC(+) and I-309(+)
      inflammatory cells and the mean values of the three groups differed significantly
      (17.0 (SD 10.1); 9.5 (9.9), and 4.3 (7.9), respectively, p = 0.0117, ANOVA). The
      numbers of PARC(+) inflammatory cells had the strongest correlation with the
      numbers of CD3(+) T lymphocytes. Few CCR4(+) inflammatory cells were observed in
      only three specimens. Double immunohistochemistry revealed that all inflammatory
      cells expressing chemokines were CD68(+) monocytes/macrophages. The numbers of
      CD25(+) T lymphocytes were higher than the numbers of CD26(+), CD62L(+), CD71(+),
      and CD30(+) T lymphocytes and the mean values of the five groups differed
      significantly (46.2 (27.9), 30.7 (16.0), 20.1 (8.6), 7.8 (7.7), and 6.5 (4.0),
      respectively, p <0.001, ANOVA). The numbers of CD25(+) T lymphocytes had the
      strongest correlation with the numbers of CD3(+) T lymphocytes. CONCLUSION: These
      results suggest a potential role for PARC, MDC, and I-309 in attracting T
      lymphocytes into conjunctiva in VKC. T lymphocytes in VKC are activated and
      express several activation markers which might contribute to the pathogenesis of
      VKC.

PMID- 12234904
TI  - Acanthamoeba keratitis in Ghana.

PMID- 12234903
TI  - Systems of analysis of posterior capsule opacification.
AB  - This paper demonstrates the wide variety of systems for the analysis of posterior
      capsular opacification (PCO). No single system has been proved to be a gold
      standard and it is difficult to comment on the advantages of one system over
      another with the limited current knowledge on the effects of PCO on vision. There
      are few studies that actually compare the different systems of analysis.
      Researchers must ensure that the systems they use for PCO analysis are objective
      and must give maximum consideration to ensuring potential systematic errors are
      reduced to a minimum. Further research is required into how the various types and
      locations of PCO affect vision and how well different systems of analysis
      perform.

PMID- 12234905
TI  - Spontaneous venous pulsations should be monitored during glaucoma therapy.

PMID- 12234906
TI  - Uveitis initiating an autoimmune reaction resulting in Goodpasture's syndrome in
      a Chinese man.

PMID- 12234907
TI  - Need for measurement of porphyrins in teardrops in patients with congenital
      erythropoietic porphyria.

PMID- 12234908
TI  - Fusarium solani keratitis following LASIK for myopia.

PMID- 12234909
TI  - Uveal metastasis 43 years after resection of bronchogenic carcinoid.

PMID- 12234910
TI  - Recurrent corneal ulcerations with perforation in keratosis follicularis (Darier
      White disease).

PMID- 12234911
TI  - A perspective on bovine pericardium for orbital implants.

PMID- 12234912
TI  - Uveal melanoma: Finland v India.

PMID- 12234913
TI  - TTT for occult CNV: check the power!

PMID- 12234915
TI  - Nucleosome sliding: facts and fiction.
AB  - Nucleosome sliding is a frequent result of energy-dependent nucleosome
      remodelling in vitro. This review discusses the possible roles for nucleosome
      sliding in the assembly and maintenance of dynamic chromatin and for the
      regulation of diverse functions in eukaryotic nuclei.

PMID- 12234916
TI  - Atomic model of the papillomavirus capsid.
AB  - Papillomaviruses propagate in differentiating skin cells, and certain types are
      responsible for the onset of cervical cancer. We have combined image
      reconstructions from electron cryomicroscopy (cryoEM) of bovine papillomavirus at
      9 A resolution with coordinates from the crystal structure of small virus-like
      particles of the human papillomavirus type 16 L1 protein to generate an atomic
      model of the virion. The overall fit of the L1 model into the cryoEM map is
      excellent, but residues 402-446 in the 'C-terminal arm' must be rebuilt. We
      propose a detailed model for the structure of this arm, based on two constraints:
      the presence of an intermolecular disulfide bond linking residues 175 and 428,
      and the clear identification of a feature in the image reconstruction
      corresponding to an alpha-helix near the C-terminus of L1. We have confirmed the
      presence of the disulfide bond by mass spectrometry. Our 'invading arm' model
      shows that papilloma- and polyomaviruses have a conserved capsid architecture.
      Most of the rebuilt C-terminal arm is exposed on the viral surface; it is likely
      to have a role in infection and in immunogenicity.

PMID- 12234917
TI  - The structure of bacterial DnaA: implications for general mechanisms underlying
      DNA replication initiation.
AB  - The initiation of DNA replication is a key event in the cell cycle of all
      organisms. In bacteria, replication initiation occurs at specific origin
      sequences that are recognized and processed by an oligomeric complex of the
      initiator protein DnaA. We have determined the structure of the conserved core of
      the Aquifex aeolicus DnaA protein to 2.7 A resolution. The protein comprises an
      AAA+ nucleotide-binding fold linked through a long, helical connector to an all
      helical DNA-binding domain. The structure serves as a template for understanding
      the physical consequences of a variety of DnaA mutations, and conserved motifs in
      the protein suggest how two critical aspects of origin processing, DNA binding
      and homo-oligomerization, are mediated. The spatial arrangement of these motifs
      in DnaA is similar to that of the eukaryotic-like archaeal replication initiation
      factor Cdc6/Orc1, demonstrating that mechanistic elements of origin processing
      may be conserved across bacterial, archaeal and eukaryotic domains of life.

PMID- 12234918
TI  - The disulfide bond isomerase DsbC is activated by an immunoglobulin-fold thiol
      oxidoreductase: crystal structure of the DsbC-DsbDalpha complex.
AB  - The Escherichia coli disulfide bond isomerase DsbC rearranges incorrect disulfide
      bonds during oxidative protein folding. It is specifically activated by the
      periplasmic N-terminal domain (DsbDalpha) of the transmembrane electron
      transporter DsbD. An intermediate of the electron transport reaction was trapped,
      yielding a covalent DsbC-DsbDalpha complex. The 2.3 A crystal structure of the
      complex shows for the first time the specific interactions between two thiol
      oxidoreductases. DsbDalpha is a novel thiol oxidoreductase with the active site
      cysteines embedded in an immunoglobulin fold. It binds into the central cleft of
      the V-shaped DsbC dimer, which assumes a closed conformation on complex
      formation. Comparison of the complex with oxidized DsbDalpha reveals major
      conformational changes in a cap structure that regulates the accessibility of the
      DsbDalpha active site. Our results explain how DsbC is selectively activated by
      DsbD using electrons derived from the cytoplasm.

PMID- 12234919
TI  - Crystal structure of the BEACH domain reveals an unusual fold and extensive
      association with a novel PH domain.
AB  - The BEACH domain is highly conserved in a large family of eukaryotic proteins,
      and is crucial for their functions in vesicle trafficking, membrane dynamics and
      receptor signaling. However, it does not share any sequence homology with other
      proteins. Here we report the crystal structure at 2.9 A resolution of the BEACH
      domain of human neurobeachin. It shows that the BEACH domain has a new and
      unusual polypeptide backbone fold, as the peptide segments in its core do not
      assume regular secondary structures. Unexpectedly, the structure also reveals
      that the BEACH domain is in extensive association with a novel, weakly conserved
      pleckstrin-homology (PH) domain. Consistent with the structural analysis,
      biochemical studies show that the PH and BEACH domains have strong interactions,
      suggesting they may function as a single unit. Functional studies in intact cells
      demonstrate the requirement of both the PH and the BEACH domains for activity. A
      prominent groove at the interface between the two domains may be used to recruit
      their binding partners.

PMID- 12234920
TI  - Sprouty2 attenuates epidermal growth factor receptor ubiquitylation and
      endocytosis, and consequently enhances Ras/ERK signalling.
AB  - Drosophila Sprouty (dSpry) was genetically identified as a novel antagonist of
      fibroblast growth factor receptor (FGFR), epidermal growth factor receptor (EGFR)
      and Sevenless signalling, ostensibly by eliciting its response on the Ras/MAPK
      pathway. Four mammalian sprouty genes have been cloned, which appear to play an
      inhibitory role mainly in FGF- mediated lung and limb morphogenesis. Evidence is
      presented herein that describes the functional implications of the direct
      association between human Sprouty2 (hSpry2) and c-Cbl, and its impact on the
      cellular localization and signalling capacity of EGFR. Contrary to the consensus
      view that Spry2 is a general inhibitor of receptor tyrosine kinase signalling,
      hSpry2 was shown to abrogate EGFR ubiquitylation and endocytosis, and sustain EGF
      induced ERK signalling that culminates in differentiation of PC12 cells.
      Correlative evidence showed the failure of hSpry2DeltaN11 and mSpry4, both
      deficient in c-Cbl binding, to instigate these effects. hSpry2 interacts
      specifically with the c-Cbl RING finger domain and displaces UbcH7 from its
      binding site on the E3 ligase. We conclude that hSpry2 potentiates EGFR
      signalling by specifically intercepting c-Cbl-mediated effects on receptor down
      regulation.

PMID- 12234921
TI  - Pleiotropic defects in TCR signaling in a Vav-1-null Jurkat T-cell line.
AB  - The Rac/Rho-specific guanine nucleotide exchange factor, Vav-1, is a key
      component of the T-cell antigen receptor (TCR)-linked signaling machinery. Here
      we have used somatic cell gene-targeting technology to generate a Vav-1-deficient
      Jurkat T-cell line. The J.Vav1 cell line exhibits dramatic defects in TCR
      dependent interleukin (IL)-2 promoter activation, accompanied by significant
      reductions in the activities of the NFAT(IL-2), NFkappaB, AP-1 and REAP
      transcription factors that bind to the IL-2 promoter region. In contrast, loss of
      Vav-1 had variable effects on early TCR-stimulated signaling events. J.Vav1 cells
      display a selective defect in sustained Ca(2+) signaling during TCR stimulation,
      and complementation of this abnormality by exogenously introduced Vav-1 is
      dependent on the Vav-1 calponin homology domain. While JNK activation was
      severely impaired, the stimulation of Ras, ERK and protein kinase C-theta
      activities, as well as the mobilization of lipid rafts, appeared normal in the
      J.Vav1 cells. Finally, evidence is presented to suggest that the alternative Vav
      family members, Vav-2 and Vav-3, are activated during TCR ligation, and partially
      compensate for the loss of Vav-1 in Jurkat T cells.

PMID- 12234922
TI  - Modulation of T-lymphocyte development, growth and cell size by the Myc
      antagonist and transcriptional repressor Mad1.
AB  - Activated lymphocytes must increase in size and duplicate their contents (cell
      growth) before they can divide. The molecular events that control cell growth in
      proliferating lymphocytes and other metazoan cells are still unclear. Here, we
      utilized transgenesis to provide evidence suggesting that the basic helix-loop-
      helix-zipper (bHLHZ) transcriptional repressor Mad1, considered to be an
      antagonist of Myc function, inhibits lymphocyte expansion, maturation and growth
      following pre-T-cell receptor (pre-TCR) and TCR stimulation. Furthermore, we
      utilized cDNA microarray technology to determine that, of the genes repressed by
      Mad1, the majority (77%) are involved in cell growth, which correlates with a
      decrease in size of Mad1 transgenic thymocytes. Over 80% of the genes repressed
      by Mad1 have previously been found to be induced by Myc. These results suggest
      that a balance between Myc and Mad levels may normally modulate lymphocyte
      proliferation and development in part by controlling expression of growth
      regulating genes.

PMID- 12234923
TI  - Induction of COX-2 by LPS in macrophages is regulated by Tpl2-dependent CREB
      activation signals.
AB  - Macrophage activation by bacterial lipopolysaccharide (LPS) promotes the
      secretion of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF
      alpha) and interleukin-1beta (IL-1beta), and of secondary mediators, such as
      leukotrienes and prostaglandins (PGs). Mice lacking the gene encoding the
      serine/threonine protein kinase Tpl2/Cot produce low levels of TNF-alpha in
      response to LPS because of an ERK-dependent post-transcriptional defect, and they
      are resistant to LPS/D-galactosamine-induced endotoxin shock. In this study we
      demonstrate that prostaglandin E2 and its regulatory enzyme, COX-2, are also
      targets of Tpl2-transduced LPS signals in bone marrow-derived mouse macrophages.
      Thus, LPS-stimulated Tpl2(-/-) macrophages express low levels of COX-2 and PGE2,
      compared with wild-type Tpl2(+/+) cells. The ability of Tpl2 to regulate COX-2
      expression depends on ERK signals that activate p90Rsk and Msk1, which in turn
      phosphorylate CREB, a key regulator of COX-2 transcription. These data identify
      physiological targets of Tpl2 signaling downstream of ERK and further implicate
      Tpl2 in the pathophysiology of inflammation.

PMID- 12234924
TI  - Nonself recognition is mediated by HET-C heterocomplex formation during
      vegetative incompatibility.
AB  - Nonself recognition during vegetative growth in filamentous fungi is mediated by
      heterokaryon incompatibility (het) loci. In Neurospora crassa, het-c is one of 11
      het loci. Three allelic specificity groups, termed het-c(OR), het-c(PA) and het
      c(GR), exist in natural populations. Heterokaryons or partial diploids that
      contain het-c alleles of alternative specificity show severe growth inhibition,
      repression of conidiation and hyphal compartmentation and death (HCD). Using
      epitope-tagged HET-C, we show that nonself recognition is mediated by the
      presence of a heterocomplex composed of polypeptides encoded by het-c alleles of
      alternative specificity. The HET-C heterocomplex localized to the plasma membrane
      (PM); PM-bound HET-C heterocomplexes occurred in all three het-c incompatible
      allelic interactions. Strains containing het-c constructs deleted for a predicted
      signal peptide sequence formed HET-C heterocomplexes in the cytoplasm and showed
      a growth arrest phenotype. Our finding is a step towards understanding nonself
      recognition mechanisms that operate during vegetative growth in filamentous
      fungi, and provides a model for investigating relationships between recognition
      mechanisms and cell death.

PMID- 12234925
TI  - A role for cell polarity proteins in mitotic exit.
AB  - The budding yeast mitotic exit network (MEN) is a signal transduction cascade
      that controls exit from mitosis by facilitating the release of the cell cycle
      phosphatase Cdc14 from the nucleolus. The G protein Tem1 regulates MEN activity.
      The Tem1 guanine nucleotide exchange factor (GEF) Lte1 associates with the cortex
      of the bud and activates the MEN upon the formation of an anaphase spindle. Thus,
      the cell cortex has an important but ill-defined role in MEN regulation. Here, we
      describe a network of conserved cortical cell polarity proteins that have key
      roles in mitotic exit. The Rho-like GTPase Cdc42, its GEF Cdc24 and its effector
      Cla4 [a member of the p21-activated kinases (PAKs)] control the initial binding
      and activation of Lte1 to the bud cortex. Moreover, Cdc24, Cdc42 and Ste20,
      another PAK, probably function parallel to Lte1 in facilitating mitotic exit.
      Finally, the cell polarity proteins Kel1 and Kel2 are present in complexes with
      both Lte1 and Tem1, and negatively regulate mitotic exit.

PMID- 12234926
TI  - Fission yeast Mor2/Cps12, a protein similar to Drosophila Furry, is essential for
      cell morphogenesis and its mutation induces Wee1-dependent G(2) delay.
AB  - Fission yeast cells identify growing regions at the opposite ends of the cell,
      producing the rod-like shape. The positioning of the growth zone(s) and the
      polarized growth require CLIP170-like protein Tip1 and the Ndr kinase Orb6,
      respectively. Here, we show that the mor2/cps12 mutation disrupts the
      localization of F-actin at the cell ends, producing spherical cells and
      concomitantly inducing a G(2) delay at 36 degrees C. Mor2 is important for the
      localization of F-actin at the cell end(s) but not at the medial region, and is
      essential for the restriction of the growth zone(s) where Tip1 targets. Mor2 is
      homologous to the Drosophila Furry protein, which is required to maintain the
      integrity of cellular extensions, and is localized at both cell ends and the
      medial region of the cell in an actin-dependent fashion. Cellular localization of
      Mor2 and Orb6 was interdependent. The tyrosine kinase Wee1 is necessary for the
      G(2) delay and maintenance of viability of the mor2 mutant. These results
      indicate that Mor2 plays an essential role in cell morphogenesis in concert with
      Orb6, and the mutation activates the mechanism coordinating morphogenesis with
      cell cycle progression.

PMID- 12234927
TI  - Dual mode of degradation of Cdc25 A phosphatase.
AB  - The Cdc25 dual-specificity phosphatases control progression through the
      eukaryotic cell division cycle by activating cyclin-dependent kinases. Cdc25 A
      regulates entry into S-phase by dephosphorylating Cdk2, it cooperates with
      activated oncogenes in inducing transformation and is overexpressed in several
      human tumors. DNA damage or DNA replication blocks induce phosphorylation of
      Cdc25 A and its subsequent degradation via the ubiquitin-proteasome pathway. Here
      we have investigated the regulation of Cdc25 A in the cell cycle. We found that
      Cdc25 A degradation during mitotic exit and in early G(1) is mediated by the
      anaphase-promoting complex or cyclosome (APC/C)(Cdh1) ligase, and that a KEN-box
      motif in the N-terminus of the protein is required for its targeted degradation.
      Interestingly, the KEN-box mutated protein remains unstable in interphase and
      upon ionizing radiation exposure. Moreover, SCF (Skp1/Cullin/F-box) inactivation
      using an interfering Cul1 mutant accumulates and stabilizes Cdc25 A. The presence
      of Cul1 and Skp1 in Cdc25 A immunocomplexes suggests a direct involvement of SCF
      in Cdc25 A degradation during interphase. We propose that a dual mechanism of
      regulated degradation allows for fine tuning of Cdc25 A abundance in response to
      cell environment.

PMID- 12234928
TI  - VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of
      phosphorylation and cell contacts.
AB  - VE-cadherin is the essential adhesion molecule in endothelial adherens junctions,
      and the regulation of protein tyrosine phosphorylation is thought to be important
      for the control of adherens junction integrity. We show here that VE-PTP
      (vascular endothelial protein tyrosine phosphatase), an endothelial receptor-type
      phosphatase, co-precipitates with VE-cadherin, but not with beta-catenin, from
      cell lysates of transfected COS-7 cells and of endothelial cells. Co
      precipitation of VE-cadherin and VE-PTP required the most membrane-proximal
      extracellular domains of each protein. Expression of VE-PTP in triple-transfected
      COS-7 cells and in CHO cells reversed the tyrosine phosphorylation of VE-cadherin
      elicited by vascular endothelial growth factor receptor 2 (VEGFR-2). Expression
      of VE-PTP under an inducible promotor in CHO cells transfected with VE-cadherin
      and VEGFR-2 increased the VE-cadherin-mediated barrier integrity of a cellular
      monolayer. Surprisingly, a catalytically inactive mutant form of VE-PTP had the
      same effect on VE-cadherin phosphorylation and cell layer permeability. Thus, VE
      PTP is a transmembrane binding partner of VE-cadherin that associates through an
      extracellular domain and reduces the tyrosine phosphorylation of VE-cadherin and
      cell layer permeability independently of its enzymatic activity.

PMID- 12234929
TI  - Single-molecule investigation of the interference between kinesin, tau and MAP2c.
AB  - Motor proteins and microtubule-associated proteins (MAPs) play important roles in
      cellular transport, regulation of shape and polarity of cells. While motor
      proteins generate motility, MAPs are thought to stabilize the microtubule tracks.
      However, the proteins also interfere with each other, such that MAPs are able to
      inhibit transport of vesicles and organelles in cells. In order to investigate
      the mechanism of MAP-motor interference in molecular detail, we have studied
      single kinesin molecules by total internal reflection fluorescence microscopy in
      the presence of different neuronal MAPs (tau, MAP2c). The parameters observed
      included run-length (a measure of processivity), velocity and frequency of
      attachment. The main effect of MAPs was to reduce the attachment frequency of
      motors. This effect was dependent on the concentration, the affinity to
      microtubules and the domain composition of MAPs. In contrast, once attached, the
      motors did not show a change in speed, nor in their run-length. The results
      suggest that MAPs can regulate motor activity on the level of initial attachment,
      but not during motion.

PMID- 12234930
TI  - The light subunit of system b(o,+) is fully functional in the absence of the
      heavy subunit.
AB  - The heteromeric amino acid transporters are composed of a type II glycoprotein
      and a non-glycosylated polytopic membrane protein. System b(o,+) exchanges
      dibasic for neutral amino acids. It is composed of rBAT and b(o,+)AT, the latter
      being the polytopic membrane subunit. Mutations in either of them cause
      malfunction of the system, leading to cystinuria. b(o,+)AT-reconstituted systems
      from HeLa or MDCK cells catalysed transport of arginine that was totally
      dependent on the presence of one of the b(o,+) substrates inside the liposomes.
      rBAT was essential for the cell surface expression of b(o,+)AT, but it was not
      required for reconstituted b(o,+)AT transport activity. No system b(o,+)
      transport was detected in liposomes derived from cells expressing rBAT alone. The
      reconstituted b(o,+)AT showed kinetic asymmetry. Expressing the cystinuria
      specific mutant A354T of b(o,+)AT in HeLa cells together with rBAT resulted in
      defective arginine uptake in whole cells, which was paralleled by the
      reconstituted b(o,+)AT activity. Thus, subunit b(o,+)AT by itself is sufficient
      to catalyse transmembrane amino acid exchange. The polytopic subunits may also be
      the catalytic part in other heteromeric transporters.

PMID- 12234931
TI  - Disabled-2 exhibits the properties of a cargo-selective endocytic clathrin
      adaptor.
AB  - Clathrin-coated pits at the cell surface select material for transportation into
      the cell interior. A major mode of cargo selection at the bud site is via the
      micro 2 subunit of the AP-2 adaptor complex, which recognizes tyrosine-based
      internalization signals. Other internalization motifs and signals, including
      phosphorylation and ubiquitylation, also tag certain proteins for incorporation
      into a coated vesicle, but the mechanism of selection is unclear. Disabled-2
      (Dab2) recognizes the FXNPXY internalization motif in LDL-receptor family members
      via an N-terminal phosphotyrosine-binding (PTB) domain. Here, we show that in
      addition to binding AP-2, Dab2 also binds directly to phosphoinositides and to
      clathrin, assembling triskelia into regular polyhedral coats. The FXNPXY motif
      and phosphoinositides contact different regions of the PTB domain, but can stably
      anchor Dab2 to the membrane surface, while the distal AP-2 and clathrin-binding
      determinants regulate clathrin lattice assembly. We propose that Dab2 is a
      typical member of a growing family of cargo-specific adaptor proteins, including
      beta-arrestin, AP180, epsin, HIP1 and numb, which regulate clathrin-coat assembly
      at the plasma membrane by synchronizing cargo selection and lattice
      polymerization events.

PMID- 12234932
TI  - Distinct mechanisms of E2F regulation by Drosophila RBF1 and RBF2.
AB  - RBF1, a Drosophila pRB family homolog, is required for cell cycle arrest and the
      regulation of E2F-dependent transcription. Here, we describe the properties of
      RBF2, a second family member. RBF2 represses E2F transcription and is present at
      E2F-regulated promoters. Analysis of in vivo protein complexes reveals that RBF1
      and RBF2 interact with different subsets of E2F proteins. dE2F1, a potent
      transcriptional activator, is regulated specifically by RBF1. In contrast, RBF2
      binds exclusively to dE2F2, a form of E2F that functions as a transcriptional
      repressor. We find that RBF2-mediated repression requires dE2F2. More over, RBF2
      and dE2F2 act synergistically to antagonize dE2F1-mediated activation, and they
      co-operate to block S phase progression in transgenic animals. The network of
      interactions between RBF1 or RBF2 and dE2F1 or dE2F2 reveals how the activities
      of these proteins are integrated. These results suggest that there is a
      remarkable degree of symmetry in the arrangement of E2F and RB family members in
      mammalian cells and in DROSOPHILA.

PMID- 12234933
TI  - Alternating translocation of protein substrates from both ends of ClpXP protease.
AB  - In ClpXP protease complexes, hexameric rings of the ATP-dependent ClpX chaperone
      stack on one or both faces of the double-heptameric rings of ClpP. We used
      electron microscopy to record the initial binding of protein substrates to ClpXP
      and their accumulation inside proteolytically inactive ClpP. Proteins with N- or
      C-terminal recognition motifs bound to complexes at the distal surface of ClpX
      and, upon addition of ATP, were translocated to ClpP. With a partially
      translocated substrate, the non-translocated portion remained on the surface of
      ClpX, aligned with the central axis of the complex, confirming that translocation
      proceeds through the axial channel of ClpXP. Starting with substrate bound on
      both ends, most complexes translocated substrate from only one end, and rarely
      (<5%) from both ends. We propose that translocation from one side is favored for
      two reasons: initiation of translocation is infrequent, making the probability of
      simultaneous initiation low; and, further, the presence of protein within the cis
      side translocation channel or within ClpP generates an inhibitory signal blocking
      translocation from the trans side.

PMID- 12234934
TI  - Identification of p100 as a coactivator for STAT6 that bridges STAT6 with RNA
      polymerase II.
AB  - STAT6 is a central mediator of IL-4-induced gene responses. STAT6-mediated
      transcription is depend ent on the C-terminal transcription activation domain
      (TAD), but the mechanisms by which STAT6 activates transcription are poorly
      understood. Here, we have identified the staphylococcal nuclease (SN)-like domain
      and tudor domain containing protein p100 as a STAT6 TAD interacting protein. p100
      was originally characterized as a transcriptional coactivator for Epstein-Barr
      virus nuclear antigen 2. STAT6 interacted with p100 in vitro and in vivo. The
      interaction was mediated by the TAD domain of STAT6 and the SN-like domain of
      p100. p100 did not affect the immediate activation events of STAT6, but enhanced
      STAT6-mediated transcriptional activation and the IL-4-induced Igepsilon gene
      transcription in human B-cell line. Finally, p100 associated with the large
      subunit of RNA polymerase II and was mediating interaction between STAT6 and RNA
      polymerase II. These findings identify p100 as a novel coactivator for STAT6 and
      suggest that p100 functions as a bridging factor between STAT6 and the basal
      transcription machinery.

PMID- 12234935
TI  - RPD3 is required for the inactivation of yeast ribosomal DNA genes in stationary
      phase.
AB  - rRNA transcription in Saccharomyces cerevisiae is performed by RNA polymerase I
      and regulated by changes in growth conditions. During log phase, approximately
      50% of the ribosomal DNA (rDNA) genes in each cell are transcribed and maintained
      in an open, psoralen-accessible conformation. During stationary phase, the
      percentage of open rDNA genes is greatly reduced. In this study we found that the
      Rpd3 histone deacetylase was required to inactivate (close) individual rDNA genes
      as cells entered stationary phase. Even though approximately 50% of the rDNA
      genes remained open during stationary phase in rpd3Delta mutants, overall rRNA
      synthesis was still reduced. Using electron microscopy of Miller chromatin
      spreads, we found that the number of RNA polymerases transcribing each open gene
      in the rpd3Delta mutant was significantly reduced when cells grew past log phase.
      Bulk levels of histone H3 and H4 acetylation were reduced during stationary phase
      in an RPD3-dependent manner. However, histone H3 and H4 acetylation was not
      significantly altered at the rDNA locus in an rpd3Delta mutant. Rpd3 therefore
      regulates the number of open rDNA repeats.

PMID- 12234936
TI  - DNA methylation affects the cell cycle transcription of the CtrA global regulator
      in Caulobacter.
AB  - The Caulobacter chromosome changes progressively from the fully methylated to the
      hemimethylated state during DNA replication. These changes in DNA methylation
      could signal differential binding of regulatory proteins to activate or repress
      transcription. The gene encoding CtrA, a key cell cycle regulatory protein, is
      transcribed from two promoters. The P1 promoter fires early in S phase and
      contains a GAnTC sequence that is recognized by the CcrM DNA methyltransferase.
      Using analysis of CcrM mutant strains, transcriptional reporters integrated at
      different sites on the chromosome, and a ctrA P1 mutant, we demonstrate that
      transcription of the P1 promoter is repressed by DNA methylation. Moreover moving
      the native ctrA gene to a position near the chromosomal terminus, which delays
      the conversion of the ctrA promoter from the fully to the hemimethylated state
      until late in the cell cycle, inhibited ctrA P1 transcription, and altered the
      time of accumulation of the CtrA protein and the size distribution of swarmer
      cells. Together, these results show that CcrM-catalyzed methylation adds another
      layer of control to the regulation of ctrA expression.

PMID- 12234937
TI  - Characterization of novel SF3b and 17S U2 snRNP proteins, including a human Prp5p
      homologue and an SF3b DEAD-box protein.
AB  - Mass spectrometry was used to identify novel proteins associated with the human
      17S U2 snRNP and one of its stable subunits, SF3b. Several additional proteins
      were identified, demonstrating that 17S U2 snRNPs are significantly more complex
      than previously thought. Two of the newly identified proteins, namely the DEAD
      box proteins SF3b125 and hPrp5 (a homologue of Saccharomyces cerevisiae Prp5p)
      were characterized further. Immunodepletion experiments with HeLa nuclear extract
      indicated that hPrp5p plays an important role in pre-mRNA splicing, acting during
      or prior to prespliceosome assembly. The SF3b-associated protein SF3b125
      dissociates at the time of 17S U2 formation, raising the interesting possibility
      that it might facilitate the assembly of the 17S U2 snRNP. Finally,
      immunofluorescence/FISH studies revealed a differential subnuclear distribution
      of U2 snRNA, hPrp5p and SF3b125, which were enriched in Cajal bodies, versus
      SF3b155 and SF3a120, which were not; a model for 17S U2 snRNP assembly based on
      these findings is presented. Taken together, these studies provide new insight
      into the composition of the 17S U2 snRNP and the potential function of several of
      its proteins.

PMID- 12234938
TI  - Visualization of parental HSV-1 genomes and replication compartments in
      association with ND10 in live infected cells.
AB  - The relative location of active and repressed genes within the nucleus is
      becoming recognized as a significant factor in the control of gene expression. We
      have developed systems to visualize parental and replicated herpes simplex virus
      type 1 (HSV-1) amplicon genomes in association with PML nuclear bodies (ND10) in
      live cells. Plasmids containing viral replication and packaging signals, a gene
      expressing enhanced yellow fluorescent protein linked to the tetracycline
      repressor DNA binding domain and 14 copies of the tetracycline operator sequence
      were used to produce amplicon genomes packaged into normal viral particles. The
      frequency of the juxtaposition of viral genomes and ND10 was substantially
      increased by inclusion of an active HSV-1 Early gene transcription unit,
      indicating that the association is neither random nor passive. Furthermore, the
      ND10-associated genomes preferentially progressed to form viral replication
      compartments. Thus, active viral transcription contributes to the efficiency of
      viral genome association with ND10, and this in turn increases the probability
      that the genome will engage in active DNA replication. These studies in live
      cells provide a novel insight into virus-ND10 interactions and provide compelling
      visualization of their functional relevance.

PMID- 12234941
TI  - Cardiotrophin-1 in heart failure.

PMID- 12234939
TI  - Asymmetrical division of the kinetoplast DNA network of the trypanosome.
AB  - Trypanosome mitochondrial DNA is a network containing thousands of interlocked
      minicircles. Silencing of a mitochondrial topoisomerase II by RNA interference
      (RNAi) causes progressive network shrinking, allowing assessment of the minimal
      network size compatible with viability. We cloned surviving cells after short
      term RNAi and found, as expected, that the number of surviving clones decreased
      with the duration of RNAi. Unexpectedly, a clonal cell line contained
      heterogeneously sized networks, some being very small. Several experiments showed
      that cells survived network shrinkage by asymmetrical division of replicated
      networks, sacrificing daughters with the small progeny network. Therefore, the
      average network size gradually increased. During the network shrinkage and early
      stages of recovery, there were changes in the minicircle repertoire.

PMID- 12234942
TI  - Platelets, endothelial cells, inflammatory chemokines, and restenosis: complex
      signaling in the vascular play book.

PMID- 12234943
TI  - Cardiology patient pages. Pulmonary embolism and deep vein thrombosis.

PMID- 12234944
TI  - Demonstration that C-reactive protein decreases eNOS expression and bioactivity
      in human aortic endothelial cells.
AB  - BACKGROUND: C-reactive protein (CRP), the prototypic marker of inflammation, has
      been shown to be an independent predictor of cardiovascular events. Endothelial
      nitric oxide synthase (eNOS) deficiency is a pivotal event in atherogenesis.
      METHODS AND RESULTS: We tested the effect of CRP on eNOS expression and
      bioactivity in cultured human aortic endothelial cells (HAECs). CRP decreased
      eNOS mRNA, protein abundance, and enzyme activity in HAECs. Furthermore, eNOS
      bioactivity assayed by cyclic GMP levels was significantly reduced by CRP.
      Preincubation of cells with CRP also significantly increased the adhesion of
      monocytes to HAECs. CONCLUSION: CRP causes a direct reduction in eNOS expression
      and bioactivity in HAECs, further supporting its role in atherogenesis.

PMID- 12234945
TI  - Augmented expression of cardiotrophin-1 in failing human hearts is accompanied by
      diminished glycoprotein 130 receptor protein abundance.
AB  - BACKGROUND: Cardiotrophin-1 (CT-1), a member of the interleukin-6 superfamily, is
      a potent inducer of cardiomyocyte hypertrophy that prolongs myocyte survival.
      Although cardiac CT-1 gene expression is known to be upregulated in some animal
      models of congestive heart failure, the activation state of the CT-1 system in
      patients with congestive heart failure is unknown. METHODS AND RESULTS: This
      study was designed to determine left ventricular expression of CT-1 and its
      glycoprotein 130 (gp130)/leukemia inhibitory factor receptor complex in human end
      stage heart failure due to ischemic and dilated cardiomyopathy. In addition, we
      investigated the activation state of signal transducer and activator of
      transcription 3 (STAT3), the downstream effector of gp130 signaling. In the
      failing left ventricular myocardium, expression levels of CT-1 mRNA and protein
      were significantly increased by 142% and 68%, respectively, compared with non
      failing donor hearts. Immunohistochemistry confirmed the increased expression of
      CT-1 in cardiac myocytes. Although gp130 gene expression was increased by 91%
      (P<0.001), gp130 protein abundance was significantly diminished by 34% in the
      failing myocardium. In contrast, leukemia inhibitory factor receptor and
      suppressor of cytokine signaling-3 protein concentrations were not changed. In
      addition, the ratio of activated tyrosine phosphorylated STAT3 to total STAT3 was
      not significantly altered in failing hearts compared with non-failing controls.
      CONCLUSIONS: Our data suggest that gp130 receptor downregulation balances
      enhanced CT-1 expression in human heart failure and thereby inhibits excessive
      activation of the gp130 signaling pathway.

PMID- 12234946
TI  - Simvastatin lowers C-reactive protein within 14 days: an effect independent of
      low-density lipoprotein cholesterol reduction.
AB  - BACKGROUND: The early response of C-reactive protein to initiation of a
      hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) is not known. The
      purpose of this study was to determine the rate at which highly sensitive C
      reactive protein (hsCRP) levels change after initiation of simvastatin and
      whether this occurs independently of the change in LDL cholesterol. METHODS AND
      RESULTS: The study was a crossover, double-blind design including 40 subjects
      with elevated LDL cholesterol. Subjects were randomly assigned to 1 of 2 groups:
      simvastatin 40 mg for 14 days, then placebo for 14 days, or placebo first, then
      simvastatin. Simvastatin decreased LDL cholesterol by 56+/-4 mg/dL (P<0.0001) at
      day 7 and by an additional 8+/-3 mg/dL (P=0.02) at day 14. Baseline log(hsCRP)
      levels were similar in the 2 groups. By day 14, log(hsCRP) was significantly
      lower in patients on simvastatin when compared with placebo (P=0.011). Although
      there was no significant difference in fibrinogen levels, simvastatin produced a
      modest increase in log[lipoprotein(a)] (P=0.03) at days 7 and 14. There were no
      relationships between the decrease in LDL cholesterol and the decrease in hsCRP.
      CONCLUSIONS: Simvastatin lowers hsCRP by 14 days, independent of its effect on
      LDL cholesterol. This rapid impact of a statin on hsCRP has potential
      implications in the management of acute coronary syndromes.

PMID- 12234947
TI  - Alpha-tocopherol supplementation in healthy individuals reduces low-density
      lipoprotein oxidation but not atherosclerosis: the Vitamin E Atherosclerosis
      Prevention Study (VEAPS).
AB  - BACKGROUND: Epidemiological studies have demonstrated an inverse relationship
      between vitamin E intake and cardiovascular disease (CVD) risk. In contrast,
      randomized controlled trials have reported conflicting results as to whether
      vitamin E supplementation reduces atherosclerosis progression and CVD events.
      METHODS AND RESULTS: The study population consisted of men and women > or =40
      years old with an LDL cholesterol level > or =3.37 mmol/L (130 mg/dL) and no
      clinical signs or symptoms of CVD. Eligible participants were randomized to DL
      alpha-tocopherol 400 IU per day or placebo and followed every 3 months for an
      average of 3 years. The primary trial end point was the rate of change in the
      common carotid artery far-wall intima-media thickness (IMT) assessed by computer
      image-processed B-mode ultrasonograms. A mixed effects model using all
      determinations of IMT was used to test the hypothesis of treatment differences in
      IMT change rates. Compared with placebo, alpha-tocopherol supplementation
      significantly raised plasma vitamin E levels (P<0.0001), reduced circulating
      oxidized LDL (P=0.03), and reduced LDL oxidative susceptibility (P<0.01).
      However, vitamin E supplementation did not reduce the progression of IMT over a 3
      year period compared with subjects randomized to placebo. CONCLUSIONS: The
      results are consistent with previous randomized controlled trials and extend the
      null results of vitamin E supplementation to the progression of IMT in healthy
      men and women at low risk for CVD.

PMID- 12234948
TI  - High doses of vitamin C reverse Escherichia coli endotoxin-induced hyporeactivity
      to acetylcholine in the human forearm.
AB  - BACKGROUND: Acute inflammation causes endothelial vasodilator dysfunction that
      may be mediated by oxidative stress. METHODS AND RESULTS: In this randomized,
      double-blind, crossover study, forearm blood flow responses to acetylcholine
      (ACh) (endothelium-dependent dilator) and glyceryl-trinitrate (GTN) (endothelium
      independent dilator) were assessed before and after induction of acute systemic
      inflammation by low doses of Escherichia coli endotoxin (LPS) (20 IU/kg IV) in 8
      healthy volunteers. The acute effect of intra-arterial vitamin C (24 mg/min) or
      placebo was studied 4 hours after LPS, respectively. Vitamin C alone was
      administered in control experiments. LPS administration caused systemic
      vasodilation, increased white blood count, elevated body temperature, and reduced
      vitamin C plasma concentrations. LPS decreased the responses of forearm blood
      flow to ACh by 30% (P<0.05) but not to GTN. Vitamin C completely restored the
      response to ACh, which was comparable with that observed under baseline
      conditions. Vitamin C had no effect on basal blood flow or ACh- or GTN-induced
      vasodilation in control subjects. CONCLUSIONS: Our data demonstrate that impaired
      endothelial vasodilation caused by E coli endotoxemia can be counteracted by high
      doses of antioxidants in vivo. Oxidative stress may play an important role in the
      pathogenesis of endothelial dysfunction during inflammation.

PMID- 12234949
TI  - Wine drinking and risks of cardiovascular complications after recent acute
      myocardial infarction.
AB  - BACKGROUND: Scientific data on the clinical impact of moderate alcohol
      consumption after a recent acute myocardial infarction (AMI) are limited, and the
      specific effect of wine ethanol has not been studied. METHODS AND RESULTS: In
      survivors of a recent AMI, we analyzed the association between ethanol intake and
      the risk of recurrence. The patients were classified according to the amount of
      ethanol that they consumed regularly during follow-up. Major prognostic factors,
      including the severity of the prior AMI and drug treatment, were recorded and
      included in the analyses. Only patients with at least 2 reliable assessments of
      drinking (and dietary) habits were included (n=437). The average ethanol intake
      was 7.6% of the total energy intake, wherein wine ethanol represented 92% of the
      total. Among these patients, 104 cardiovascular complications occurred during a
      mean follow-up period of 4 years. In comparison with abstainers, the adjusted
      risk of complications was reduced by 59% (95% confidence interval: 17 to 80) in
      patients whose average ethanol intake was 7.7% of the total energy intake (about
      2 drinks/day), and by 52% (95% confidence interval: 4 to 76) in those whose
      average ethanol intake was of 16% of energy (about 4 drinks/day). CONCLUSION:
      Whereas moderate wine drinking was associated with a significant reduction in the
      risk of complications in this homogenous population of coronary heart disease
      patients, further studies are required to confirm the data, define the clinical
      and biological profile of the patients who would most benefit from wine drinking
      after recent AMI, and examine whether the relations found are due to ethanol or
      other wine ingredients.

PMID- 12234950
TI  - Randomized COMparison of platelet inhibition with abciximab, tiRofiban and
      eptifibatide during percutaneous coronary intervention in acute coronary
      syndromes: the COMPARE trial. Comparison Of Measurements of Platelet aggregation
      with Aggrastat, Reopro, and Eptifibatide.
AB  - BACKGROUND: The relative anti-aggregatory effects of currently prescribed
      platelet glycoprotein IIb/IIIa receptor antagonists during and after percutaneous
      coronary intervention for acute coronary syndromes have not been established.
      METHODS AND RESULTS: We randomized 70 acute coronary syndrome patients undergoing
      percutaneous coronary intervention to receive abciximab, eptifibatide, or
      tirofiban at doses used in the Evaluation of Platelet IIb/IIIa Inhibitor for
      STENTing (EPISTENT), Platelet glycoprotein IIb/IIIa in Unstable angina Receptor
      Suppression Using Integrilin Therapy (PURSUIT), and Platelet Receptor Inhibition
      in ischemic Syndrome Management in Patients Limited by Unstable Signs and
      symptoms (PRISM-PLUS)/Randomized Efficacy Study of Tirofiban for Outcomes and
      Restenosis (RESTORE) trials, respectively. Platelet aggregation (PA) in response
      to 20 micro mol/L of adenosine diphosphate was measured with turbidimetric
      aggregometry in both D-phenylalanyl-L-prolyl-L-arginine chloromethylketone and
      citrate-anticoagulated blood early (15 and 30 minutes) and late (4, 12, and 18 to
      24 hours) after drug initiation. At 15 and 30 minutes, PA was significantly less
      inhibited by the tirofiban-RESTORE regimen compared with abciximab (P=0.028) and
      eptifibatide regimens (P=0.0001). The abciximab regimen, however, showed
      increasingly varied anti-aggregatory effects during continued infusion for > or
      =4 hours. Citrate exaggerated ex vivo platelet inhibition after eptifibatide and
      tirofiban, but had the opposite effect on abciximab. Of all regimens evaluated,
      the eptifibatide regimen inhibited PA most consistently throughout both the early
      and late periods. CONCLUSIONS: Currently recommended drug regimens to inhibit the
      platelet glycoprotein IIb/IIIa receptor have distinct pharmacodynamic profiles
      that might affect their relative efficacy in acute coronary syndromes and
      percutaneous coronary intervention.

PMID- 12234951
TI  - Survival in primary pulmonary hypertension: the impact of epoprostenol therapy.
AB  - BACKGROUND: Primary pulmonary hypertension (PPH) is a severe and progressive
      disease. Without treatment, the median survival is 2.8 years, with survival rates
      of 68%, 48%, and 34% at 1, 3, and 5 years, respectively. Intravenous epoprostenol
      was the first Food and Drug Administration-approved therapy for PPH. The long
      term impact that epoprostenol has made on PPH remains to be defined. METHODS AND
      RESULTS: One hundred sixty-two consecutive patients diagnosed with PPH and
      treated with epoprostenol were followed for a mean of 36.3 months (median, 31
      months). Data including functional class, exercise tolerance, and hemodynamics
      were recorded in a customized database. Vital status was verified in each
      patient. Observed survival with epoprostenol therapy at 1, 2, and 3 years was
      87.8%, 76.3%, and 62.8% and was significantly greater than the expected survival
      of 58.9%, 46.3%, and 35.4% based on historical data. Baseline predictors of
      survival included exercise tolerance, functional class, right atrial pressure,
      and vasodilator response to adenosine. Predictors of survival after the first
      year of therapy included functional class and improvement in exercise tolerance,
      cardiac index, and mean pulmonary artery pressure. CONCLUSIONS: Intravenous
      epoprostenol improves long-term survival in PPH.

PMID- 12234952
TI  - Angiotensinogen gene promoter region variant modifies body size-ambulatory blood
      pressure relations in hypertension.
AB  - BACKGROUND: The extent to which genes modify the relationship between risk
      factors for hypertension and blood pressure (BP) is unclear. As angiotensinogen
      is expressed in adipose tissue and angiotensinogen (AGT) gene promoter variants
      influence the production of angiotensinogen, we evaluated the role of AGT gene
      variants as potential modifiers of body size-BP relations. METHODS AND RESULTS:
      Five hundred twenty-one hypertensives of African origin sampled from a group with
      a high mean body mass index (BMI) had 24-hour ambulatory BP (ABP) measurements
      determined off therapy and were genotyped for the AGT -6G-->A, -532C-->T, -20A-
      >C, and 704T-->C (M235T) gene variants. Genotypes were also determined in 547
      control subjects of African origin who had a normal clinic BP. The -6A and -532C
      alleles were concordant with the M235T variant. Although AGT gene variants had no
      independent effects on either the presence of hypertension or ABP values in
      hypertensives, the -20A-->C polymorphism had a marked influence on the relation
      between ambulatory systolic BP and BMI. This relation was present in patients
      homozygous for the -20A allele (n=399, r=0.23, P<0.0001), but absent in those
      with at least one copy of the -20C allele (n=122, r=0.01, P=0.89). The M235T
      polymorphism did not impact on the BMI-BP relation. Specificity of the -20A-->C
      polymorphism effect on the BMI-BP relation is further indicated by the lack of
      effect on the systolic BP-age relation. CONCLUSION: An AGT gene promoter region
      variant is an important modifier of the relation between body size and BP. Hence,
      these data corroborate the notion that genetic modifiers can produce a profound
      impact on BP-phenotypic relations.

PMID- 12234953
TI  - Sex-selective QT prolongation during rapid eye movement sleep.
AB  - BACKGROUND: We examined the effects of the various sleep stages on RR and QT
      intervals in healthy subjects and tested the hypothesis that there is a
      differential effect of sleep stage on QT interval in women compared with men.
      METHODS AND RESULTS: Eighteen healthy subjects (9 women, age 22 to 45 years)
      underwent polysomnography and simultaneous recording of ECG, blood pressure, and
      respiration. RR interval, RR variability, and QT values were measured in stable
      conditions (no abrupt changes of heart rate or blood pressure, stable breathing
      pattern) during inactive wakefulness during stages 2 and 3 to 4 of non-REM sleep
      and during REM sleep. The absolute QT interval was normalized for variations of
      RR (QTc). In men, RR interval and RR variability increased through all sleep
      stages. The QTc remained stable from wakefulness through all sleep stages. In
      women, however, RR interval increased only during non-REM and was virtually
      identical in wakefulness and in REM. RR variability remained very stable from
      wakefulness through all stages of sleep. Also, during REM in women, both absolute
      QT interval and QTc, regardless of the correction maneuver used, increased
      compared with wakefulness. CONCLUSIONS: The influence of sleep on RR, RR
      variability, and QTc is sex-dependent. We speculate that these differential sex
      effects on cardiac rate and repolarization may have important implications for
      sleep-selected cardiac arrhythmias in women.

PMID- 12234954
TI  - Human cardiac inwardly-rectifying K+ channel Kir(2.1b) is inhibited by direct
      protein kinase C-dependent regulation in human isolated cardiomyocytes and in an
      expression system.
AB  - BACKGROUND: Protein kinases A (PKA) and C (PKC) are activated in ischemic
      preconditioning and heart failure, conditions in which patients develop
      arrhythmias. The native inward rectifier potassium current (IK1) plays a central
      role in the stabilization of the resting membrane potential and the process of
      arrhythmogenesis. This study investigates the functional relationship between PKC
      and IK1. METHODS AND RESULTS: In whole-cell patch-clamp experiments with isolated
      human atrial cardiomyocytes, the IK1 was reduced by 41% when the nonspecific
      activator of PKC phorbol 12 myristate 13-acetate (PMA; 100 nmol/L) was applied.
      To investigate the effects of PKC on cloned channel underlying parts of the
      native IK1, we expressed Kir(2.1b) heterologously in Xenopus oocytes and measured
      currents with the double-electrode voltage-clamp technique. PMA decreased the
      current by an average of 68%, with an IC50 of 0.68 nmol/L. The inactive compound
      4-alpha-PMA was ineffective. Thymeleatoxin and 1-oleolyl-2-acetyl-sn-glycerol, 2
      specific activators of PKC, produced effects similar to those of PMA. Inhibitors
      of PKC, ie, staurosporine and chelerytrine, could inhibit the PMA effect (1
      nmol/L) significantly. After mutation of the PKC phosphorylation sites
      (especially S64A and T353A), PMA became ineffective. CONCLUSIONS: The human IK1
      in atrial cardiomyocytes and one of its underlying ion channels, the Kir(2.1b)
      channel, is inhibited by PKC-dependent signal transduction pathways, possibly
      contributing to arrhythmogenesis in patients with structural heart disease in
      which PKC is activated.

PMID- 12234955
TI  - Serotonin reuptake inhibitor (Paxil) does not prevent the vasovagal reaction
      associated with carotid sinus massage and/or lower body negative pressure in
      healthy volunteers.
AB  - BACKGROUND: The purpose of this study was to assess the effect of the serotonin
      reuptake inhibitor paroxetine hydrochloride (Paxil, SmithKline Beecham) on
      cardiovascular reflexes. We hypothesized that Paxil prevents neurally mediated
      syncope (NMS) by attenuating the sympathoinhibition and vagotonia associated with
      a vasovagal reaction. METHODS AND RESULTS: In a double-blind randomized study, 25
      healthy subjects with a positive response to either carotid sinus massage (CSM)
      or lower body negative pressure (LBNP) received Paxil (20 mg/d) or placebo for 6
      weeks. Arterial baroreflex sensitivity (BRS), muscle sympathetic nerve activity
      (SNA), baroreflex control of SNA, blood pressure, and heart rate responses to CSM
      and LBNP were measured at baseline and at 6 weeks. Nineteen subjects completed
      the study (Paxil, n=9; placebo, n=10). In the Paxil group, BRS decreased
      significantly compared with baseline (15.8+/-4.0 ms/mm Hg versus 11.0+/-2.6 ms/mm
      Hg, P=0.05); however, all 9 subjects continued to have a positive response to
      LBNP with presyncope. Paxil did not attenuate the sympathoinhibition or vagotonia
      associated with a positive LBNP response and had no significant effect on
      baroreflex control of SNA. In the control group, no significant change in BRS was
      noted compared with baseline. Seven out of 9 subjects who had a positive LBNP
      response at baseline had a repeat positive LBNP response, and the subject with a
      positive CSM at baseline had a negative response at 6 weeks. CONCLUSIONS: Paxil
      decreases arterial BRS but does not prevent the presyncope associated with LBNP.
      The effect of Paxil on the autonomic reflexes in patients with neurally mediated
      syncope remains unclear.

PMID- 12234956
TI  - Sirolimus-eluting stents for the treatment of obstructive superficial femoral
      artery disease: six-month results.
AB  - BACKGROUND: Stent implantation for obstructive femoropopliteal artery disease has
      been associated with poor long-term outcomes. This study evaluated the
      effectiveness of shape memory alloy recoverable technology (SMART) nitinol self
      expanding stents coated with a polymer impregnated with sirolimus (rapamycin)
      versus uncoated SMART stents in superficial femoral artery obstructions. METHODS
      AND RESULTS: Thirty-six patients were recruited for this double-blind,
      randomized, prospective trial. All patients had chronic limb ischemia and femoral
      artery occlusions (57%) or stenoses (average lesion length, 85+/-57 mm). Patients
      were eligible for randomization after successful guidewire passage across the
      lesion. Eighteen patients received sirolimus-eluting SMART stents and 18 patients
      received uncoated SMART stents. The primary end point of the study was the in
      stent mean percent diameter stenosis, as measured by quantitative angiography at
      6 months. The in-stent mean percent diameter stenosis was 22.6% in the sirolimus
      eluting stent group versus 30.9% in the uncoated stent group (P=0.294). The in
      stent mean lumen diameter was significantly larger in the sirolimus-eluting stent
      group (4.95 mm versus 4.31 mm in the uncoated stent group; P=0.047). No serious
      adverse events (death or prolonged hospitalization) were reported. CONCLUSIONS:
      The use of sirolimus-eluting SMART stents for superficial femoral artery
      occlusion is feasible, with a trend toward reducing late loss compared with
      uncoated stents. The coated stent also proved to be safe and was not associated
      with any serious adverse events.

PMID- 12234957
TI  - More accurate quantification of pulmonary blood flow by magnetic resonance
      imaging than by lung perfusion scintigraphy in patients with fontan circulation.
AB  - BACKGROUND: Quantitative evaluation of pulmonary perfusion using lung perfusion
      scintigraphy in patients with atriopulmonary anastomosis (APA) or total
      cavopulmonary connection (TCPC) or partial cavopulmonary connection (PCPC) is
      difficult because of preferential draining of the venae cavae to one lung.
      Scintigraphy is the gold standard. Phase-velocity MRI (PV-MRI) is a new technique
      for determining pulmonary perfusion. The aim of this study was therefore to
      determine whether PV-MRI is more accurate than scintigraphy for quantitative
      evaluation of pulmonary perfusion ratios in patients with APA, TCPC, or PCPC.
      METHODS AND RESULTS: We studied 15 patients with APA, TCPC, or PCPC (16+/-7 years
      old, 4 female). Twelve patients (15+/-8 years old, 3 female) with a single
      pulmonary blood source supplied by a subpulmonary ventricle, ensuring complete
      mixing of the radioactive tracer before entering the pulmonary circulation,
      served as controls. Pulmonary scintigraphy and PV-MRI were performed in all
      patients. Bland-Altman analysis showed a clinically unacceptable difference of
      7.1% right pulmonary blood flow (27.2% upper and -13.0% lower limit of agreement)
      between the two methods in the study group. The two methods agreed excellently in
      the control group (difference, 1.6%; 4.0% upper and -7.2% lower limit of
      agreement), showing that the bad agreement in the study group was caused by the
      problems encountered using pulmonary scintigraphy in patients with APA, TCPC, or
      PCPC. CONCLUSIONS: Because of preferential caval flow into either lung, PV-MRI is
      more accurate for evaluating pulmonary perfusion ratios than lung perfusion
      scintigraphy in patients with Fontan-like circulation.

PMID- 12234958
TI  - Female sex as a risk factor for in-hospital mortality among children undergoing
      cardiac surgery.
AB  - BACKGROUND: The purpose of this study was to investigate whether sex disparity in
      cardiovascular outcomes exists in children who undergo cardiac surgery. METHODS
      AND RESULTS: Statewide hospital discharge data from California from 1995 to 1997
      were used. Children <21 years old who had a procedure code (by ICD9-CM) that
      indicated cardiac surgery were selected. The outcome variable was binary, in
      hospital death versus alive at discharge. Twenty-three surgical procedures were
      selected and adjusted for risk by procedure type. We used logistic regression
      analysis to evaluate the effect of sex on in-hospital mortality, controlling for
      age, race and ethnicity, type of insurance, home income, type of admission, date
      and month of surgery, hospital case volume, and type of procedure. There were
      6593 cases of cardiac surgery, with 345 in-hospital deaths (mortality rate
      5.23%). Crude mortality rates for males (4.98%) and females (5.54%) were not
      significantly different. However, fewer females were neonates, and females had
      more low-risk procedures than males. Multivariate logistic regression showed that
      females had a higher odds ratio (OR) for mortality than males (OR 1.51, P<0.01).
      The OR for mortality was 3.86 for neonates and 2.98 for infants compared with
      children aged > or =1 year. Low-volume hospitals had higher mortality rates than
      high-volume hospitals (OR 1.67, P<0.01). The risk-adjusted length of hospital
      stay and charges were similar between females and males. CONCLUSIONS: For
      children undergoing cardiac surgery, female sex was associated with 51% higher
      odds of death than male sex. The mechanism by which female sex acts as a risk
      factor requires further investigation.

PMID- 12234959
TI  - Deposition of platelet RANTES triggering monocyte recruitment requires P-selectin
      and is involved in neointima formation after arterial injury.
AB  - BACKGROUND: Chemokines expressed on atherosclerotic endothelium or deposited by
      activated platelets have been implicated in monocyte recruitment during
      atherogenesis and restenosis. Although the involvement of P-selectin in these
      processes is evident from studies in knockout mice, it has not been elucidated
      whether delivery of platelet chemokines requires P-selectin, thus serving as a P
      selectin-dependent effector function. METHODS AND RESULTS: Using
      immunofluorescence and laminar flow assays, we found that the deposition of the
      platelet-derived chemokine RANTES and monocyte arrest subsequently triggered by
      RANTES immobilized on inflamed endothelium are more efficient after preperfusion
      than after static preincubation of platelets and appear to depend on interactions
      of platelet but not endothelial P-selectin. This was revealed by the effects of P
      selectin antibodies and comparison of P-selectin-deficient and wild-type
      platelets. Immunohistochemistry detected a substantial luminal expression of
      RANTES on neointimal lesions in wire-injured carotid arteries of apolipoprotein E
      (apoE)-deficient mice but not of mice with a combined deficiency in apoE and P
      selectin (or platelet P-selectin). As assessed by histomorphometry, treatment of
      apoE-deficient mice with the RANTES receptor antagonist Met-RANTES markedly
      reduced neointimal plaque area and macrophage infiltration. CONCLUSIONS: Our data
      suggest that RANTES deposition and subsequent monocyte arrest are promoted by
      platelet P-selectin and involved in wire-induced intimal hyperplasia, and that
      blocking RANTES receptors attenuates neointima formation and macrophage
      infiltration. This mechanism represents an important component explaining the
      protection against neointimal growth in P-selectin-deficient mice and may
      represent a novel approach to the treatment of restenosis or atherosclerosis by
      the administration of chemokine receptor antagonists.

PMID- 12234960
TI  - Protective function of transcription factor TR3 orphan receptor in atherogenesis:
      decreased lesion formation in carotid artery ligation model in TR3 transgenic
      mice.
AB  - BACKGROUND: Smooth muscle cells (SMCs) play a key role in intimal thickening in
      atherosclerosis and restenosis. The precise signaling pathways by which the
      proliferation of SMCs is regulated are largely unknown. The TR3 orphan receptor,
      the mitogen-induced nuclear orphan receptor (MINOR), and the nuclear receptor of
      T cells (NOT) are a subfamily of transcription factors belonging to the nuclear
      receptor superfamily and are induced in activated SMCs. In this study, we
      investigated the role of these transcription factors in SMC proliferation in
      atherogenesis. METHODS AND RESULTS: Multiple human vascular specimens at distinct
      stages of atherosclerosis (lesion types II to V by American Heart Association
      classification) derived from 14 different individuals were studied for expression
      of these transcription factors. We observed expression of TR3, MINOR, and NOT in
      neointimal SMCs, whereas no expression was detected in medial SMCs. Adenovirus
      mediated expression of a dominant-negative variant of TR3, which suppresses the
      transcriptional activity of each subfamily member, increases DNA synthesis and
      decreases p27(Kip1) protein expression in cultured SMCs. We generated transgenic
      mice that express this dominant-negative variant or full-length TR3 under control
      of a vascular SMC-specific promoter. Carotid artery ligation of transgenic mice
      that express the dominant-negative variant of TR3 in arterial SMCs, compared with
      lesions formed in wild-type mice, results in a 3-fold increase in neointimal
      formation, whereas neointimal formation is inhibited 5-fold in transgenic mice
      expressing full-length TR3. CONCLUSIONS: Our results reveal that TR3 and possibly
      other members of this transcription factor subfamily inhibit vascular lesion
      formation. These transcription factors could serve as novel targets in the
      treatment of vascular disease.

PMID- 12234961
TI  - Overexpression of soluble fas attenuates transplant arteriosclerosis in rat
      aortic allografts.
AB  - BACKGROUND: The killing of vascular cells by activated macrophages is an
      important step in the process of destabilization of the arterial wall. The death
      receptor Fas is implicated in vascular cell death. Hence, we extended our studies
      in a rat aortic allograft model, using adenovirus-mediated overexpression of
      soluble Fas (sFas) to block Fas binding to Fas ligand (Fas-L). The contribution
      of Fas to vascular cell injury and consequent transplant arteriosclerosis was
      investigated. METHODS AND RESULTS: Activated monocytes in the presence of
      macrophage colony-stimulating factor induce endothelial cell apoptosis in vitro,
      which was significantly inhibited by adenovirus-mediated sFas overexpression.
      Next, donor rat abdominal aortas were either untreated or transduced with
      adenoviruses encoding (1) rat soluble Fas (Ad3rsFas), (2) no insert (Ad3Null),
      and (3) beta-galactosidase (Ad3nBg). A total of 175 aortic grafts were harvested
      2 to 90 days after transplantation. Vascular cell apoptosis and CD45+ cell
      infiltration were significantly reduced in Ad3rsFas-transduced aortas, as
      compared with control allografts. Moreover, the control allografts developed
      marked intimal thickening, whereas Ad3rsFas-transduced allografts had
      significantly less neointima until the 90-day time point. CONCLUSIONS: sFas
      overexpression protects the integrity of the vessel wall from immune injury and
      attenuates transplant arteriosclerosis.

PMID- 12234962
TI  - Intracellular action of matrix metalloproteinase-2 accounts for acute myocardial
      ischemia and reperfusion injury.
AB  - BACKGROUND: Matrix metalloproteinases are best recognized for their ability to
      degrade the extracellular matrix in both physiological and pathological
      conditions. However, recent findings indicate that some of them are also involved
      in mediating acute processes such as platelet aggregation and vascular tone. The
      acute contractile defect of the heart after ischemia-reperfusion may involve the
      proteolytic degradation of the thin filament protein troponin I; however, the
      protease responsible for this remains obscure. METHODS AND RESULTS: Here we
      report that matrix metalloproteinase-2 is colocalized with troponin I within the
      thin myofilaments of cardiomyocytes in ischemic-reperfused hearts and that
      troponin I is a novel intracellular target for proteolytic cleavage by matrix
      metalloproteinase-2. Inhibition of matrix metalloproteinase-2 activity prevented
      ischemia-reperfusion-induced troponin I degradation and improved the recovery of
      mechanical function of the heart. CONCLUSIONS: These data reveal for the first
      time a novel molecular mechanism by which matrix metalloproteinase-2 causes acute
      myocardial dysfunction after ischemia-reperfusion-injury and that matrix
      metalloproteinase-2 has a biological action within the cell.

PMID- 12234963
TI  - Stimulation of arteriogenesis in skeletal muscle by microbubble destruction with
      ultrasound.
AB  - BACKGROUND: The application of ultrasound to microbubbles in skeletal muscle
      creates capillary ruptures. We tested the hypothesis that this bioeffect could be
      used to stimulate the growth and remodeling of new arterioles via natural repair
      processes, resulting in an increase in skeletal muscle nutrient blood flow.
      METHODS AND RESULTS: Pulsed ultrasound (1 MHz) was applied to exposed rat
      gracilis muscle after intravenous microbubble injection. Capillary rupturing was
      visually verified by the presence of red blood cells in the muscle, and animals
      were allowed to recover. Ultrasound-microbubble-treated and contralateral sham
      treated muscles were harvested 3, 7, 14, and 28 days later. Arterioles were
      assessed by smooth muscle alpha-actin staining, and skeletal muscle blood flow
      was measured with 15- micro m fluorescent microspheres. An approximately 65%
      increase in arterioles per muscle fiber was noted in treated muscles compared
      with paired sham-treated control muscles at 7 and 14 days after treatment. This
      increase in arterioles occurred across all studied diameter ranges at both 7 and
      14 days after treatment. Arterioles per muscle fiber in sham-treated and
      untreated control muscles were comparable, indicating that the surgical
      intervention itself had no significant effect. Hyperemia nutrient blood flow in
      treated muscles was increased 57% over that in paired sham-treated control
      muscles. CONCLUSIONS: Capillary rupturing via microbubble destruction with
      ultrasound enhances arterioles per muscle fiber, arteriole diameters, and maximum
      nutrient blood flow in skeletal muscle. This method has the potential to become a
      clinical tool for stimulating blood flow to organs affected by occlusive vascular
      disease.

PMID- 12234964
TI  - K(ATP) channel gene expression is induced by urocortin and mediates its
      cardioprotective effect.
AB  - BACKGROUND: Urocortin is a novel cardioprotective agent that can protect cardiac
      myocytes from the damaging effects of ischemia/reperfusion both in culture and in
      the intact heart and is effective when given at reperfusion. METHODS AND RESULTS:
      We have analyzed global changes in gene expression in cardiac myocytes after
      urocortin treatment using gene chip technology. We report that urocortin
      specifically induces enhanced expression of the Kir 6.1 cardiac potassium channel
      subunit. On the basis of this finding, we showed that the cardioprotective effect
      of urocortin both in isolated cardiac cells and in the intact heart is
      specifically blocked by both generalized and mitochondrial-specific K(ATP)
      channel blockers, whereas the cardioprotective effect of cardiotrophin-1 is
      unaffected. Conversely, inhibiting the Kir 6.1 channel subunit greatly enhances
      cardiac cell death after ischemia. CONCLUSIONS: This is, to our knowledge, the
      first report of the altered expression of a K(ATP) channel subunit induced by a
      cardioprotective agent and demonstrates that K(ATP) channel opening is essential
      for the effect of this novel cardioprotective agent.

PMID- 12234965
TI  - Treatment of acute ischemic stroke: Part I: recanalization strategies.

PMID- 12234966
TI  - Images in cardiovascular medicine. Effect of percutaneous transluminal
      angioplasty on severely stenotic femoral lesions: in vivo demonstration by
      noninvasive magnetic resonance imaging.

PMID- 12234967
TI  - Guidelines for the reporting of renal artery revascularization in clinical
      trials. American Heart Association.

PMID- 12234968
TI  - Images in cardiovascular medicine. Percutaneous heart valve in the chronic in
      vitro testing model.

PMID- 12234969
TI  - Recent clinical trial updates.

PMID- 12234970
TI  - Impact of revised criteria for myocardial infarction.

PMID- 12234971
TI  - Cancer prevention science and practice.

PMID- 12234972
TI  - Wnt signaling regulates expression of the receptor tyrosine kinase met in
      colorectal cancer.
AB  - Overexpression of the receptor tyrosine kinase Met is an early event in the
      colorectal adenoma-carcinoma sequence. This suggests a link with disruption of
      adenomatous polyposis coli-controlled regulation of beta-catenin/T-cell factor
      (TCF)-mediated transcriptional activation, which is crucial in initiating
      tumorigenesis. Indeed, in intestinal biopsies from patients with familial
      adenomatous polyposis, we find Met already overexpressed in dysplastic aberrant
      crypt foci, the earliest neoplastic lesions of colorectal cancer (CRC). Moreover,
      in CRC cells, induction of dominant-negative TCF proteins and the consequent
      abrogation of beta-catenin/TCF-mediated transcriptional activation lead to a
      strong down-regulation of Met expression. Our results indicate that Met
      expression is part of a genetic program controlled by the Wnt pathway and suggest
      a role for Met in controlling the turnover and differentiation of intestinal
      epithelium.

PMID- 12234973
TI  - Direct association of TSLC1 and DAL-1, two distinct tumor suppressor proteins in
      lung cancer.
AB  - The tumor suppressor gene TSLC1, which we recently identified in human non-small
      cell lung cancer, encodes a membrane glycoprotein of the immunoglobulin
      superfamily. Here, we report that TSLC1 directly associates with DAL-1, a gene
      product of another lung tumor suppressor belonging to the protein 4.1 family.
      TSLC1 additionally interacts with the actin filament through DAL-1 at the cell
      cell attached site where the complex formation of TSLC1 and DAL-1 is dependent on
      the integrity of actin cytoskeleton. Redistribution of both TSLC1 and DAL-1 to
      the newly generated membrane ruffling areas suggests that these proteins are also
      involved in cell motility accompanying the actin rearrangement. Furthermore,
      restoration of TSLC1 expression strongly suppressed the metastasis of a human non
      small cell lung cancer cell line, A549, from the spleen to the liver in nude
      mice. These findings, together with frequent loss of their expression in lung
      cancers, suggest that TSLC1 and DAL-1 play a critical role in the same pathway
      involved in the suppression of lung tumor formation and metastasis.

PMID- 12234974
TI  - Cell lineage-specific effects associated with multiple deficiencies of tumor
      susceptibility genes in Msh2(-/-)Rb(+/-) mice.
AB  - Cooperative effects of genetic alterations are frequently observed during
      carcinogenesis. Mice carrying germ-line mutations in both Rb and p53 or Msh2 and
      p53 die earlier of tumors than mice with only one of these genes inactivated.
      Mice with a single wild-type Rb allele develop a syndrome of multiple
      neuroendocrine neoplasia, and inactivation of both alleles of Msh2 gene
      predisposes mice to gastrointestinal cancer, lymphomas and tumors of the skin
      that exhibit a mismatch repair defect. Here we showed that Msh2(-/-)Rb(+/-) mice
      developed lymphomas later than Msh2-deficient littermates, and the lymphomas
      observed in Msh2(-/-)Rb(+/-) mice have increased rates of apoptosis and rarely
      spread to other organs and tissues. In contrast to lymphomagenesis, courses of
      neuroendocrine, intestinal, and skin carcinogenesis were not significantly
      influenced by the Msh2(-/-)Rb(+/-) genetic combination. In these mice,
      neuroendocrine tumors displayed a loss of the remaining wild-type Rb allele but
      did not show microsatellite instability. On the other hand, the intestinal and
      skin tumors exhibited microsatellite instability but kept the remaining wild-type
      allele of Rb. Taken together, these data not only revealed a novel biological
      interaction between Rb and Msh2 but also cell lineage specificity effects
      associated with multiple deficiencies in these tumor susceptibility genes.

PMID- 12234975
TI  - Arginine-glycine-aspartic acid (RGD)-peptide binds to both tumor and tumor
      endothelial cells in vivo.
AB  - Targeting tumor cells or tumor vasculature by peptides is a promising strategy
      for delivering cytotoxic drugs for cancer therapy. The identification of
      efficient targeting peptides depends on the availability of informative methods
      for determining cellular binding specificities. Here, we have used fluorescence
      activated cell-sorting (FACS) analysis in combination with an isopentane freezing
      method to show targeted binding of the Arg-Gly-Asp (RGD)-4C-peptide labeled with
      FITC, not only to endothelial cells but also to tumor cells in human breast
      cancer xenografts grown in nude mice. Nontumorous cells showed only background
      binding. This study suggests, that the RGD-4C-peptide can target tumor
      endothelial cells as well as tumor cells. Consequently, it should be possible to
      design a combination therapy approach against both targets.

PMID- 12234976
TI  - Expression of a "self-"antigen by human tumor cells enhances tumor antigen
      specific CD4(+) T-cell function.
AB  - CD4(+) T cells can recognize "self" tumor antigens, but the impact of tumor cell
      expression of self-antigens on CD4(+) T-cell function in humans is unknown. Here,
      we identify a new epitope (ISPNSVFSQWRVVCDSLEDYD) derived from tyrosinase-related
      protein-1 (TRP-1) using a predictive algorithm and mice transgenic for a chimeric
      HLA-DRB1*0401 molecule. We then compared the functions of TRP-1-epitope-specific,
      CD4(+) T-cell responses in normal healthy individuals to those found in patients
      with metastatic malignant melanoma. Surprisingly, we found that tumor-bearing
      patients had significantly higher levels of TRP-1-specific, CD4(+) T-cell
      function than healthy volunteers as measured ex vivo. Thus, the net effect of
      "self" antigen expression by tumor cells was the enhancement of tumor antigen
      specific CD4(+) T-cell function, rather than immunosuppression. These findings
      indicate that antigens expressed by malignant melanoma cells can partially
      activate CD4(+) T lymphocytes.

PMID- 12234977
TI  - In vivo interferon regulatory factor 3 tumor suppressor activity in B16 melanoma
      tumors.
AB  - Delivery of transcription factors to cancer cells to reprogram gene expression
      may represent a novel strategy to augment the production of immune stimulatory
      cytokines and trigger a more potent antitumor response. In the present study, a
      bicistronic retroviral vector (AP2) was used to transduce B16-F0 melanoma cells
      with IFN regulatory factor (IRF)-3, which has been shown to activate type I IFN
      genes (IFN-beta and IFN-alpha) as well as other cytokines. Gene-modified B16
      melanoma cells were inoculated s.c. into C57BL/6 syngeneic mice. In animals
      receiving IRF-3 B16 melanoma cells, tumors grew at a 4- to 5-fold reduced rate,
      and tumors that developed from these mice had a moderate-to-dense infiltration of
      inflammatory cells, whereas only low levels of lymphocyte infiltration were
      observed in mock-transduced B16 tumors. Furthermore, tumor growth was not
      inhibited in severe-combined immunodeficient mice after inoculation of IRF-3
      expressing B16 cells, which suggested that IRF-3-mediated antitumor responses
      were dependent on a functional adaptive lymphocyte response. Interestingly, these
      in vivo effects on tumor growth correlated with higher mRNA expression of
      chemokines such as MIP-1beta, RANTES, and IP-10, as well as dramatic increases in
      vitro in the inducibility of cytokine mRNA such as IFN-beta, TNF-alpha and
      interleukin 6. Our results demonstrate that with weakly antigenic tumors such as
      B16 melanoma, IRF-3 gene transfer can mediate important antitumor responses.
      These findings suggest a novel role for IRF-3 as a potential molecular target for
      gene therapy of cancer.

PMID- 12234978
TI  - Prevention of thymic lymphoma development in Atm-/- mice by dexamethasone.
AB  - We have reported (M. Yan et al., FASEB J., 15: 1132-1138, 2001) that spontaneous
      DNA synthesisis markedly increased in the thymocytes from the atrophied thymi of
      young Atm-/- mice. We, therefore, set out to determine whether this elevated DNA
      synthesis is responsible for the development of thymic lymphomas in all Atm-/-
      mice by 4-5 months of age. We show here that in Atm-/- mice: (a) increased DNA
      synthesis occurs, especially in the immature CD4(-) CD8(-) (dominant negative)
      and CD8(+) thymocyte populations; (b) the relative percentage of dominant
      negative cells increases significantly during postnatal development, with a sharp
      peak at 4 weeks of age; and (c) dexamethasone suppresses DNA synthesis in these
      thymocytes and prevents thymic lymphoma development. These observations suggest
      that ataxia telangiectasia mutated (ATM) down-regulates the proliferation of
      thymocytes, allowing T-cell development and differentiation. The results also
      show that dexamethasone, like ATM, checks DNA synthesis in developing thymocytes.
      Finally, the data document for the first time that dexamethasone prevents or
      slows thymic lymphoma development in Atm-/- mice.

PMID- 12234979
TI  - GADD153 and 12-lipoxygenase mediate fenretinide-induced apoptosis of
      neuroblastoma.
AB  - The synthetic retinoid fenretinide induces apoptosis of neuroblastoma cells and
      in vitro acts synergistically with chemotherapeutic drugs used to treat
      neuroblastoma. The mechanisms of fenretinide-induced cell death of neuroblastoma
      cells are complex, involving cellular signaling pathways as yet incompletely
      defined but, in part, involving the generation of reactive oxygen species (ROS).
      In an attempt to characterize the mechanism of action of fenretinide, cDNA array
      filters were screened to identify apoptotic genes regulated in response to
      treatment of SH-SY5Y cells with fenretinide. Expression of the stress-induced
      transcription factor, GADD153, was up-regulated at both the protein and mRNA
      levels in response to fenretinide. Overexpression of GADD153 increased apoptosis
      in the presence and absence of fenretinide, whereas reduced expression of GADD153
      by expression of antisense DNA abrogated the response to fenretinide. Although
      fenretinide is a partial retinoic acid receptor (RAR)-beta/gamma agonist,
      RARbeta/gamma antagonists did not block the induction of GADD153 by fenretinide;
      conversely, the induction of GADD153 was blocked by antioxidants. Enzyme
      inhibitors were used to identify pathways mediating the ROS-dependent effects of
      fenretinide: inhibitors of phospholipase A(2) and lypoxygenases (LOX), and
      specific inhibitors of 12-LOX, but not 5-LOX or 15-LOX, inhibited the induction
      of ROS, apoptosis, and GADD153 in response to fenretinide. The inhibition of ROS
      and apoptosis was reversed by the addition of the 12-LOX products, 12 (S)
      hydroperoxyeicosatetraenoic acid (12-HpETE) and 12 (S)-hydroxyeicosatetraenoic
      acid (12-HETE). Fenretinide did not increase free arachidonic acid levels, but
      increased LOX activity without a detectable increase in 12-LOX protein. These
      results suggest that fenretinide induces apoptosis via RAR-dependent and 
      independent pathways in which the RAR-independent pathway is characterized by a
      fenretinide-dependent increase in 12-LOX activity, leading to the induction of
      GADD153. The targeting of 12-LOX and/or GADD153 in neuroblastoma cells may thus
      present a novel pathway for the development of drugs inducing apoptosis of
      neuroblastoma with improved tumor specificity.

PMID- 12234980
TI  - Increased mitotic phosphorylation of histone H3 attributable to AIM-1/Aurora-B
      overexpression contributes to chromosome number instability.
AB  - Phosphorylation of histone H3 at Ser-10 is required for maintenance of
      properchromosome dynamics during mitosis. AIM-1, a mammalian Ipl1/aurora kinase
      involved in H3 phosphorylation, is transcriptionally overexpressed in many tumor
      cell lines. Increased expression of the AIM-1 gene has been observed in human
      colorectal tumors of advanced grade and stage. Here we report that forced
      exogenous overexpression of AIM-1 in Chinese hamster embryo cells causes
      increased mitotic Ser-10 phosphorylation with concomitant induction of lagging
      chromosomes during mitosis. Lagging chromosomes could also be induced by
      transfection with mutated histone H3 (S10E), which is thought to maintain Ser-10
      in the phosphorylated state. In the present study, chromosome number instability
      and increased tumor invasiveness were noted in constitutively AIM-1
      overexpressing cells in vivo. Increased mitotic Ser-10 phosphorylation was also
      observed in various colorectal tumor cells with high AIM-1 expression levels.
      These data suggest that increased H3 histone phosphorylation as a result of AIM-1
      overexpression is a major precipitating factor of chromosome instability and,
      thus, may play a role in carcinogenesis.

PMID- 12234981
TI  - 9-cis-retinoic acid but not 4-(hydroxyphenyl)retinamide inhibits prostate
      intraepithelial neoplasia in Noble rats.
AB  - In most previous studies, the incidence and multiplicity of chemically induced
      prostate tumors have been used as end points for assessing the efficacy of
      various chemopreventive agents. In this study, we used prostate intraepithelial
      neoplasia (PIN) in Noble rats as an intermediate end point to examine the
      chemopreventive efficacy of two retinoids, 9-cis-retinoic acid (9cRA) and 4
      (hydroxyphenyl)retinamide, which in previous studies have shown promising
      inhibitory effects on various carcinogenesis models. We found that 80-100% of
      Noble rats treated for 36 weeks with testosterone + 17beta-estradiol developed
      multiple PIN lesions predominantly in the dorso-lateral prostate, which appears
      relevant to the place of origin of PIN and carcinoma in the human prostate. 9cRA
      at 50 or 100 mg/kg diet significantly decreased the multiplicity of PIN, whereas
      4-(hydroxyphenyl) retinamide at 392 or 784 mg/kg diet, did not have an inhibitory
      effect on PIN. Thus, we provide for the first time evidence that the testosterone
      + 17beta-estradiol-induced PIN in Noble rats could be used as a potential
      intermediate end point in assessing the efficacy of retinoids and possibly of
      other agents on prostate carcinogenesis, and that 9cRA alone or in combination
      with other agents may have clinical promise in preventing the development of
      prostate cancer in men.

PMID- 12234982
TI  - Differential induction of N(2),3-ethenoguanine in rat brain and liver after
      exposure to vinyl chloride.
AB  - Although vinyl chloride (VC) clearly induces hepatic angiosarcoma in humans and
      rodents, a causal association with brain tumors has not been definitively
      established with the available epidemiological and experimental evidence. Because
      VC acts by genotoxic mechanisms, DNA adduct formation is thought to be a
      sensitive biomarker of early events in carcinogenesis. Adult male Sprague Dawley
      rats were exposed to 0 or 1100 ppm VC for 1 or 4 weeks (6 h/day, 5 days/week) by
      inhalation. Male weanlings were similarly exposed for 5 days. Another group of
      male adults was exposed to 1100 ppm [(13)C(2)]VC in a nose-only inhalation
      apparatus for 5 days (6 h/day). A sensitive gas chromatography high-resolution
      mass spectrometry assay was used to measure the major promutagenic DNA adduct,
      N(2),3-ethenoguanine (N(2),3-epsilonG), in rat brain and hepatocyte (HEP) DNA.
      The respective concentrations of N(2),3-epsilonG in control rat brain DNA at 1
      and 4 weeks were 5.0 +/- 0.9 and 5.6 +/- 1.1 N(2),3-epsilonG/10(8) unmodified
      guanine. There was no change in N(2),3-epsilonG in adult rat brain after exposure
      to 1100 ppm VC for 1 or 4 weeks. In HEPs from the same animals, these adduct
      concentrations increased from 5.5 +/- 1.4 to 55 +/- 2.0 N(2),3-epsilonG/10(8)
      unmodified guanine after a 1-week exposure and from 3.0 +/- 0.3 to 110 +/- 20
      N(2),3-epsilonG/10(8) unmodified guanine after a 4-week exposure. When weanlings
      were exposed to 1100 ppm VC for 5 days, there was a statistically significant (P
      = 0.04) increase in N(2),3-epsilonG in brain from 1.5 +/- 0.2 to 4.4 +/- 1.1
      N(2),3-epsilonG/10(8) unmodified guanine. Weanlings exposed to 1100 ppm VC had an
      even greater increase in N(2),3-epsilonG in HEPs from 1.6 +/- 0.1 to 97 +/- 5.0
      N(2),3-epsilonG/10(8) unmodified guanine. [(13)C(2)]N(2),3-epsilonG was not
      detected in brain DNA from adult rats exposed to 1100 ppm [(13)C(2)]VC for 5 days
      but was present in HEP DNA at 55 +/- 4.0 [(13)C(2)]N(2),3-epsilonG/10(8)
      unmodified guanine. The concentrations of the endogenous adduct in both organs
      were unchanged after this exposure. 7-(Oxoethyl)guanine (OEG), the major DNA
      adduct formed by VC, was reduced to 7-(2-hydroxyethyl)guanine and measured by
      liquid chromatography-electrospray ionization-tandom mass spectrometry in brain
      and HEP DNA from rats exposed to 1100 ppm VC for 1 week. Whereas 4.0 +/- 0.8
      OEG/10(6) unmodified guanine were present in HEP DNA from VC-exposed rats, no
      adducts were detectable in brain DNA (detection limit, 0.3 OEG/10(6) unmodified
      guanine). These findings indicate that the genotoxic metabolite of VC is not
      formed in or transported to adult rat brain. Thus, it is unlikely that N(2),3
      epsilonG or other VC-induced promutagenic DNA adducts play a significant role in
      initiating carcinogenesis in adult rat brain after exposure to VC. The data for
      weanling rats are less clear. Whereas a small increase in N(2),3-epsilonG in the
      brains of weanlings was found after exposure to 1100 ppm VC, the resulting adduct
      concentration was similar to that measured in unexposed adults. Future exposures
      of weanling rats to the stable isotopically labeled compound will be necessary to
      conclusively determine whether this increase was due to VC.

PMID- 12234983
TI  - Molecular dosimetry and repair of N(2),3-ethenoguanine in rats exposed to vinyl
      chloride.
AB  - Although the DNA adducts of vinyl chloride (VC) have been well characterized,
      previous studies have used single concentrations of VC that are well above
      contemporary human exposures. This study examined the exposure response to VC in
      male Sprague Dawley rats with respect to the molecular dose of the promutagenic
      DNA adduct N(2),3-ethenoguanine (N(2),3-epsilonG). Adult rats were exposed by
      inhalation to 0, 10, 100, or 1100 ppm VC for 1 or 4 weeks (6 h/day, 5 days/week).
      Weanling rats were similarly exposed for 5 days. The amount of N(2),3-epsilonG in
      hepatocyte (HEP) and nonparenchymal cell (NPC) fractions obtained from the liver
      was measured with a sensitive immunoaffinity/gas chromatography/high-resolution
      mass spectrometry assay. Endogenous N(2),3-epsilonG was present in HEPs and NPCs
      from all unexposed rats. The exposure response to VC in each group and cell
      population was supralinear, with a linear increase from 0 to 100 ppm, and a
      plateau between 100 and 1100 ppm. There was no statistically significant
      difference in N(2),3-epsilonG concentrations between HEPs and NPCs in any adult
      exposure group, which suggests that factors other than adduct concentrations
      contribute to the particular susceptibility of NPCs to VC-induced carcinogenesis.
      The accumulation of N(2),3-epsilonG with respect to time was nearly linear in
      rats exposed to 600 ppm VC for 1, 2, 4, or 8 weeks (4 h/day, 5 days/week), and no
      repair of N(2),3-epsilonG was detected in rats exposed to VC for 4 weeks and
      allowed to recover for 1 week. N(2),3-epsilonG concentrations in HEPs from
      weanling rats were 2-3-fold greater than those in adult rats exposed for the same
      time. Higher adduct concentrations in young rats may contribute to their greater
      susceptibility to VC-induced hepatic angiosarcoma as well as their particular
      susceptibility to hepatocellular carcinoma. The molecular dosimetry of N(2),3
      epsilonG in liver appears to be a sensitive and informative biomarker of
      genotoxic effect after exposure to VC. N(2),3-epsilonG was the predominant etheno
      adduct measured in vivo after exposure to VC, and the saturable nature of VC
      metabolism was reflected in its molecular dose. The relationships between
      endogenous N(2),3-epsilonG and that formed by low exposures to VC were
      demonstrated. Conclusions drawn from these exposures may be more relevant for
      risk assessment purposes than those drawn from high exposures where activation,
      detoxication, and repair pathways may be saturated or otherwise perturbed. These
      data are well suited for consideration in future risk assessments of VC that
      incorporate nontumor mode of action data.

PMID- 12234984
TI  - Identification of Nrf2-regulated genes induced by the chemopreventive agent
      sulforaphane by oligonucleotide microarray.
AB  - Electrophiles formed during metabolic activation of chemical carcinogens and
      reactive oxygen species generated from endogenous and exogenous sources play a
      significant role in carcinogenesis. Cancer chemoprevention by induction of phase
      2 proteins to counteract the insults of these reactive intermediates has gained
      considerable attention. Nuclear factor E2 p45-related factor 2 (Nrf2), a bZIP
      transcription factor, plays a central role in the regulation (basal and or
      inducible expression) of phase 2 genes by binding to the "antioxidant response
      element" in their promoters. Identification of novel Nrf2-regulated genes is
      likely to provide insight into cellular defense systems against the toxicities of
      electrophiles and oxidants and may define effective targets for achieving cancer
      chemoprevention. Sulforaphane is a promising chemopreventive agent that exerts
      its effect by strong induction of phase 2 enzymes via activation of Nrf2. In the
      present study, a transcriptional profile of small intestine of wild-type (nrf2
      +/+) and knock out (nrf2 -/-) mice treated with vehicle or sulforaphane (9
      micromol/day for 1 week, p.o.) was generated using the Murine Genome U74Av2
      oligonucleotide array (representing approximately 6000 well-characterized genes
      and nearly 6000 expressed sequence tags). Comparative analysis of gene expression
      changes between different treatment groups of wild-type and nrf2-deficient mice
      facilitated identification of numerous genes regulated by Nrf2 including
      previously reported Nrf2-regulated genes such as NAD(P)H:quinone reductase
      (NQO1), glutathione S-transferase (GST), gamma-glutamylcysteine synthetase (GCS),
      UDP-glucuronosyltransferases (UGT),epoxide hydrolase, as well as a number of new
      genes. Also identified were genes encoding for cellular NADPH regenerating
      enzymes (glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and
      malic enzyme), various xenobiotic metabolizing enzymes, antioxidants (glutathione
      peroxidase, glutathione reductase, ferritin, and haptaglobin), and biosynthetic
      enzymes of the glutathione and glucuronidation conjugation pathways. The data
      were validated by Northern blot analysis and enzyme assays of selected genes.
      This investigation expands the horizon of Nrf2-regulated genes, highlights the
      cross-talk between various metabolic pathways, and divulges the pivotal role
      played by Nrf2 in regulating cellular defenses against carcinogens and other
      toxins.

PMID- 12234985
TI  - PC-SPES inhibits colon cancer growth in vitro and in vivo.
AB  - PC-SPES is a mixture of eight herbs with antiproliferative activity in prostate
      cancer cell lines and antitumor effects in animal models of prostate cancer. In
      addition, evidence of clinical efficacy in advanced prostate cancer has been
      reported. PC-SPES has also been shown to have antitumor activity against several
      other cancer cell lines including breast and neuroepithelial cancer, melanoma,
      and leukemia cell lines. Because of these findings, we investigated the effects
      of PC-SPES in vitro in colon cancer cell lines SW480, SW620, and DLD-1 and in
      vivo in the Apc(min) mouse, a murine model for intestinal carcinogenesis. For the
      in vitro studies, colon cancer cell lines were exposed to an ethanolic extract of
      PC-SPES compared with a diluent control [ethanol < or = 0.3% (v/v)]. PC-SPES
      resulted in a marked suppression of cell proliferation in all colon cancer cells
      studied. PC-SPES (3 micro l/ml) caused a 95% inhibition of cell proliferation of
      the DLD-1 colon cancer cell line, and similar results were observed in the SW480
      and SW620 colon cancer cell lines. Cell cycle analysis demonstrated a drastic (>
      or =60%) accumulation of cells in the G(2)-M phase with a concomitant decrease of
      cells in the G(0)-G(1) phase in all colon cancer cell lines studied after
      treatment with PC-SPES (1.5 micro l/ml for 48 h). Western blot analysis
      demonstrated a decrease in protein levels of beta-tubulin in the SW620 cell line
      exposed to PC-SPES. Terminal deoxynucleotidyl transferase-mediated nick end
      labeling analysis revealed an increase in apoptotic colon cancer cells incubated
      with PC-SPES. For the in vivo studies, female 4-5-week-old Apc(min) mice were
      randomized to two groups: a PC-SPES-treated group (n = 11) received 250 mg/kg/day
      (0.2 ml) PC-SPES via gastrointestinal gavage; and a control group (n = 10)
      received 0.2 ml of the vehicle solution (1.5% carboxymethylcellulose with 0.2%
      Tween 20) via gastrointestinal gavage. Both groups were treated five times a week
      for 10 weeks. After treatment, the gastrointestinal tract was dissected for polyp
      scoring by two observers blinded to treatment. The Apc(min) mice given PC-SPES
      had a 58% reduction in tumor number and a 56% decrease in tumor load. No effect
      on either food intake or body weight was observed in the treated versus sham
      groups. The present study is the first to report the potent activity of PC-SPES
      against colon cancer. Both cell cycle arrest and apoptosis occurred after
      treatment with PC-SPES. This suggests that the components of this herbal mixture,
      either independently or in combination, acted in colon cancer, resulting in a
      drastic effect on tumor initiation and tumor progression.

PMID- 12234986
TI  - Soluble syndecan-1 and serum basic fibroblast growth factor are new prognostic
      factors in lung cancer.
AB  - Syndecan-1 is a ubiquitous and multifunctional extracellular matrix
      proteoglycan,which mediates basic fibroblast growth factor (bFGF) binding and
      activity. Shedding of syndecan-1 ectodomain from the plasma membrane is highly
      regulated. We evaluated the influence of soluble syndecan-1 and serum bFGF
      determined by ELISA on outcome in 184 lung cancer patients (non-small cell lung
      cancer, n = 138; small cell lung cancer, n = 46). Serum syndecan-1 and bFGF
      levels were determined from sera taken before treatment. The median follow-up of
      the patients alive (n = 21) was 8.1 years (range, 6.6-8.9 years). High serum
      syndecan-1 and bFGF levels tended to occur in the same patients (P = 0.044). When
      the serum values corresponding to the highest tertile were used as the cutoff
      value, the median survival time of the patients with a high serum syndecan-1
      level (>59 ng/ml) was 4 months [95% confidence interval (CI), 3-6 months] as
      compared with 11 months (9-16 months) among those with lower serum levels (P =
      0.0001), and the median survival time of the patients with a high bFGF level
      (>3.4 pg/ml) was 5 months (3-8 months) versus 11 months (8-14 months) in those
      with a lower level (P = 0.023). In general, the prognostic influence of both
      factors was independent of the histological subtype. Both serum syndecan-1 level
      (relative risk, 1.8; 95% CI, 1.1-3.1) and serum bFGF level (relative risk, 1.6;
      95% CI, 1.0-2.7) had independent influence on survival in a multivariate survival
      analysis in non-small cell lung cancer. We conclude that high serum syndecan-1
      and bFGF levels at diagnosis are associated with poor outcome in lung cancer.

PMID- 12234987
TI  - The possible role of postoperative azotemia in enhanced survival of patients with
      metastatic renal cancer after cytoreductive nephrectomy.
AB  - Cytoreductive nephrectomy prior to systemic therapy significantly increases
      survival in patients with metastatic renal cancer. This result is generally
      ascribed to the benefits of resection of the primary tumor including reduction of
      tumor burden, removal of a source for growth factors and metastases, and enhanced
      immune response. On the basis of mathematical models of tumor invasion, we
      propose that the observed effects of cytoreductive nephrectomy may be caused by
      resection of the kidney rather than the cancer. The models predict that the
      graded metabolic acidosis associated with mild renal failure after unilateral
      nephrectomy may alter the dynamics of the tumor-host interface sufficiently to
      reduce and even reverse the rate of invasion. A review of patient data from the
      surgical arm of the Southwest Oncology Group (SWOG) 8949(2) trial demonstrates
      significantly improved survival in patients who experienced postoperative
      increase in blood urea nitrogen (BUN) and creatinine compared with those who did
      not (17-month survival versus 4-month survival; P = 0.0007). This is generally
      consistent with the predictions of the mathematical models. If confirmed, these
      results suggest novel and broadly applicable tumor therapies.

PMID- 12234988
TI  - Silencing of secretin receptor function by dimerization with a misspliced variant
      secretin receptor in ductal pancreatic adenocarcinoma.
AB  - Secretin receptors that are key for regulation of healthy pancreatic ductal
      epithelial cells have been reported to be functionally absent on ductal
      pancreatic adenocarcinomas. Here, we examine the possible presence and function
      of molecular forms of the secretin receptor in pancreatic cancer cell lines and
      in primary tumors. Surprisingly, reverse transcription-PCR and sequencing
      demonstrated wild-type secretin receptor mRNA in each of four cell lines and
      three primary tumors. Lack of biological response to nanomolar concentrations of
      secretin was best explained by the demonstrated coexpression of a second and
      predominant transcript in each of the cell lines and tumors. This represented a
      variant of the secretin receptor in which the third exon was spliced out to
      eliminate residues 44-79 from the NH(2)-terminal tail. This spliceoform has only
      recently been recognized in a rare gastrinoma, where it was incapable of binding
      secretin or signaling, and possessed dominant-negative activity to suppress
      hormone action at the wild-type secretin receptor (1). Overexpression of wild
      type secretin receptor in Panc-1 cells driven by transfection of fully processed
      cDNA resulted in normal responsiveness to low concentrations of secretin,
      establishing the ability of these cells to produce a receptor capable of normal
      biosynthesis, trafficking, and signaling. Bioluminescence resonance energy
      transfer demonstrated that the variant receptor could form a heterodimer with
      wild-type receptor, providing a molecular mechanism for its dominant-negative
      activity. This suggests that missplicing is responsible for expression of a
      secretin receptor variant having the ability to suppress the function of wild
      type receptor by a direct interaction. In 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assays in receptor-bearing Chinese hamster ovary
      cells, the secretin receptor was shown to have growth-inhibitory effects.
      Suppression of this activity in pancreatic carcinoma might, therefore, facilitate
      tumor growth and progression of this aggressive neoplasm.

PMID- 12234989
TI  - The human immunodeficiency virus (HIV)-1 protease inhibitor saquinavir inhibits
      proteasome function and causes apoptosis and radiosensitization in non-HIV
      associated human cancer cells.
AB  - Cancer cells frequently show high constitutive activity of the antiapoptotic
      transcription factor nuclear factor kappaB (NF-kappaB), which results in their
      enhanced survival. Activation of NF-kappaB classically depends on degradation of
      its inhibitor IkappaBalpha by the 26s proteasome. Specific proteasome inhibitors
      induce apoptosis in cancer cells and, at nonlethal concentrations, sensitize
      cells to the cytotoxic effects of ionizing radiation and chemotherapeutic drugs.
      Recently, the protease coded by the HIV-I virus has been shown to share cleavage
      activities with the proteasome. For this reason, we investigated whether the HIV
      I protease inhibitor saquinavir can inhibit NF-kappaB activation, block 26s
      proteasome activity in prostate cancer cells, and promote their apoptosis. The
      effect of saquinavir on LPS/IFN-gamma-induced activation of NF-kappaB was
      assessed by gel-shift assays and by Western analysis of corresponding
      IkappaBalpha-levels. Its effect on 20s and 26s proteasome activity was analyzed
      with a fluorogenic peptide assay using whole cell lysates from LnCaP, DU-145, and
      PC-3 prostate cancer cells pretreated with saquinavir for 9 h. Proteasome
      inhibition in living cells was assessed using ECV 304 cells stably transfected
      with an expression plasmid for an ubiquitin/green fluorescence protein fusion
      protein (ECV 304/10). Apoptosis was monitored morphologically and by flow
      cytometry. Saquinavir treatment prevented LPS/IFN-gamma-induced activation of NF
      kappaB in RAW cells and stabilized expression of IkappaBalpha. It inhibited 20s
      and 26s proteasome activity in lysates from LnCaP, DU-145, and PC-3 prostate
      cancer cells with an IC(50) of 10 micro M and caused the accumulation of an
      ubiquitin/green fluorescence protein fusion protein in living ECV 304/10 cells.
      Incubation of PC-3 and DU-145 prostate cancer, U373 glioblastoma, and K562 and
      Jurkat leukemia cells with saquinavir caused a concentration-dependent induction
      of apoptosis. In the case of PC-3 and DU-145, saquinavir sensitized the surviving
      cells to ionizing radiation. We conclude that saquinavir inhibits proteasome
      activity in mammalian cells as well as acting on the HIV-I protease. Because
      saquinavir induced apoptosis in human cancer cells, HIV-I protease inhibitors
      might become a new class of cytotoxic drugs, alone or in combination with
      radiation or chemotherapy.

PMID- 12234991
TI  - Inhibition of epidermal growth factor receptor signaling in malignant pleural
      mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is a rare malignancy with no known curative
      modality. Approximately 70% of MPMs have high levels of expression of the
      epidermal growth factor receptor (EGFR), and a subset of cell lines derived from
      MPM patients express both EGFR and transforming growth factor alpha, suggesting
      an autocrine role for EGFR in MPM. We have determined the effects of EGFR
      inhibition in MPM cell lines in vitro, using four MPM cell lines derived from
      previously untreated patients with epithelial (H2461 and H2591), sarcomatoid
      (H2373), and biphasic (MSTO-211H) MPM. All four cell lines expressed EGFR at
      levels comparable with the non-small cell lung carcinoma (NSCLC) cell line A549,
      as shown by Western blot analysis. ZD1839 significantly inhibited epidermal
      growth factor-dependent cell signaling including phosphorylation of AKT and
      extracellular signal-regulated kinases 1 and 2 in all MPM cell lines.
      Furthermore, treatment with ZD1839 led to a significant dose-dependent reduction
      of colony formation (41-89% at 10 microM) when MPM cells were grown in soft
      agarose. MSTO-211H, H2461, and H2373 were more sensitive to the growth-inhibitory
      effects of ZD1839 than was the NSCLC cell line A549, whereas H2591 had similar
      sensitivity to A549. This variability in growth-inhibitory effects is not related
      to the amount of EGFR present on MPM cells or to the degree of inhibition of EGFR
      phosphorylation by ZD1839. We show that H2373 MPM cells, which show 89% growth
      inhibition at 10 microM ZD1839, undergo a dose-dependent arrest at the G(1)-S
      phase of the cell cycle and a corresponding increase in p27 levels. However,
      H2591 cell lines, which show 41% growth inhibition at 10 microM ZD1839, undergo
      no significant cell cycle changes or changes in p27 levels. Our findings
      demonstrate that in vitro, ZD1839 is as effective or more effective against MPM
      cell lines as it is against the NSCLC cell line A549 and suggest that ZD1839 may
      be an effective therapeutic option for patients with MPM.

PMID- 12234990
TI  - Antifolates targeting purine synthesis allow entry of tumor cells into S phase
      regardless of p53 function.
AB  - The class of folate antimetabolites typified by (6R)-dideazatetrahydrofolate
      (lometrexol, DDATHF) are specific inhibitors of de novo purine synthesis because
      of potent inhibition of glycinamide ribonucleotide formyltransferase (GART) but
      do not induce detectable levels of DNA strand breaks. As such, they are a test
      case of the concept that ribonucleotide depletion can be sensed by p53, resulting
      in a G(1) cell cycle block. The GART inhibitors have been proposed previously to
      be cytotoxic in tumor cells lacking p53 function but only cytostatic in p53 wild
      type tumor cells. We have investigated this concept. Cell cycle progression into
      and through S phase was slowed by DDATHF, but both p53 +/+ and -/- human colon
      carcinoma cells entered and completed one S phase in the presence of drug. This
      inability of p53 to initiate a G(1) arrest after DDATHF treatment was mirrored by
      an independence of the cytotoxicity of DDATHF on p53 function. We conclude that
      carcinoma cells are killed equally well by DDATHF and related compounds whether
      or not the p53 pathway is intact and that the utility of GART inhibitors would
      not be limited to p53-negative tumors.

PMID- 12234992
TI  - Tirapazamine: a hypoxia-activated topoisomerase II poison.
AB  - Tirapazamine (TPZ), a hypoxia-selective cytotoxin, has demonstrated activity in
      cancer clinical trials. Under hypoxic conditions, TPZ is reduced to a radical
      that leads to DNA double-strand breaks (DSBs), single-strand breaks, and base
      damage. A previous finding of an association of the DSBs with protein led us to
      investigate the involvement of topoisomerase II (topo II) in their formation.
      Nuclear extracts from human lung cancer cells treated with either the topo II
      poison etoposide or TPZ under hypoxic conditions had markedly reduced topo II
      activity as judged by an inability to convert kinetoplast DNA from the catenated
      to the decatenated form. Because topo II poisons, such as etoposide, cause DNA
      DSBs, we hypothesized that pretreatment of cells with merbarone or aclarubicin,
      known catalytic inhibitors of topo II, would abrogate DNA DSBs caused by topo II.
      Cells pretreated with these catalytic inhibitors abrogated both DNA DSBs and cell
      kill induced by etoposide or by TPZ. Etoposide- and TPZ-mediated DSBs were also
      greatly reduced in a small cell lung cancer cell line with low levels of nuclear
      topo IIalpha. We also showed that topo IIalpha becomes covalently bound to DNA
      after TPZ treatment under hypoxic conditions, and that the cleavable complexes
      formed by TPZ are more stable over time than those formed by etoposide. Taken
      together, these data suggest that TPZ exerts its cytotoxic effect at least in
      part through poisoning topo II. Because TPZ is activated only under hypoxic
      conditions, which are characteristic of solid tumors, these data implicate TPZ as
      a tumor-specific topo II poison.

PMID- 12234993
TI  - Growth inhibitory effects of the dual ErbB1/ErbB2 tyrosine kinase inhibitor PKI
      166 on human prostate cancer xenografts.
AB  - Experiments with human prostate cancer cell lines have shown that forced
      overexpression of the ErbB2-receptor tyrosine kinase (RTK) promotes androgen
      independent growth and increases androgen receptor-transcriptional activity in a
      ligand-independent fashion. To investigate the relationship between ErbB-RTK
      signaling and androgen in genetically unmanipulated human prostate cancer, we
      performed biochemical and biological studies with the dual ErbB1/ErbB2 RTK
      inhibitor PKI-166 using human prostate cancer xenograft models with isogenic
      sublines reflecting the transition from androgen-dependent to androgen
      independent growth. In the presence of low androgen concentrations, PKI-166
      showed profound growth-inhibitory effects on tumor growth, which could be
      partially reversed by androgen add-back. At physiological androgen
      concentrations, androgen withdrawal greatly enhanced the ability of PKI-166 to
      retard tumor growth. The level of extracellular signal-regulated kinase
      activation correlated with the response to PKI-166 treatment, whereas the
      expression levels of ErbB1 and ErbB2 did not. These results suggest that
      ErbB1/ErbB2 RTKs play an important role in the biology of androgen-independent
      prostate cancer and provide a rationale for clinical evaluation of inhibitors
      targeted to this pathway.

PMID- 12234994
TI  - Adenovirus infection enhances dendritic cell immunostimulatory properties and
      induces natural killer and T-cell-mediated tumor protection.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells with the potential for
      cancer immunotherapy. Adenoviral-mediated gene transfer is an attractive means to
      manipulate the immunostimulatory properties of DCs for therapeutic advantage.
      Because adenovirus induces DC maturation, we postulated that it would
      significantly alter their immune functions. Infected DCs markedly increased
      allogeneic and antigen-specific T-cell proliferation, and augmented natural
      killer cell lytic activity and IFN-gamma production. The enhanced effector cell
      stimulation by infected DCs was dependent on their secretion of interleukin 12.
      Immunization with infected DCs pulsed with tumor antigen protected against flank
      tumors in 78% of mice and induced a memory response. Antitumor immunity was
      dependent on both T cells and natural killer cells. Antigen-pulsed, mock-infected
      DCs were nonprotective. The findings that adenoviral vectors alone critically
      alter DC immune functions and antitumor properties have important implications
      for the design and interpretation of immunotherapy regimens using vector-based
      gene transfer to modulate immunity.

PMID- 12234995
TI  - Inhibition of cytolytic T lymphocyte proliferation by autologous CD4+/CD25+
      regulatory T cells in a colorectal carcinoma patient is mediated by transforming
      growth factor-beta.
AB  - Cancer patients often develop CTLs that lyse autologous tumor cells in culture.
      However, tumors can progress in vivo despite the presence of CTLs. Various
      mechanisms have been reported to down-modulate CTL functions. In this study, the
      role of CD4+/CD25+ regulatory T cells in CTL induction and proliferation of
      established CTLs was investigated in a patient with CRC. CD4+ cytotoxic and
      regulatory T-cell lines were derived from the peripheral blood mononuclear cells
      of the same patient in mixed-lymphocyte tumor culture. The cytotoxic T-cell line
      and a clonal derivative specifically lysed the autologous tumor cells but not the
      B lymphocytes. Only HLA-A1-matched allogeneic CRC cells were lysed by the CTL
      clone. The clone produced IFN-gamma and TNF-alpha. The regulatory CD4+/CD25+ T
      cell line was tumor cell-dependent in its growth but did not lyse autologous
      tumor cells. This T-cell line suppressed pokeweed mitogen responses of allogeneic
      lymphocytes, proliferative activity of the established, autologous CTLs, and
      induction of CTLs in autologous, freshly isolated peripheral blood mononuclear
      cells. The immunosuppressive effect of the CD4+/CD25+ regulatory T cells was
      mediated by transforming growth factor-beta and did not require cell-to-cell
      contact. Thus, although CRC patients can develop specific CTLs against their
      tumors, the development of regulatory T cells may allow the escape of tumor cells
      from immune surveillance by the CTLs in vivo.

PMID- 12234996
TI  - The hepatocyte nuclear factor 3 alpha gene, HNF3alpha (FOXA1), on chromosome band
      14q13 is amplified and overexpressed in esophageal and lung adenocarcinomas.
AB  - Genomic amplification is observed in many, if not all, types of human malignancy
      and is one of the mechanisms for the activation of dominant-acting oncogenes in
      tumorigenesis. In the present study, three amplified restriction fragments were
      identified in an esophageal adenocarcinoma (P16) using the restriction landmark
      genome scanning two-dimensional gel technique. These fragments were cloned,
      sequenced, and mapped to chromosome band 14q13. Using the sequence tagged site
      amplification mapping approach, we defined the core-amplified domain by screening
      75 normal-tumor paired esophageal samples. The frequency of 14q13 amplification
      is 6.7% in esophageal tumors, and the amplicon spans >6 Mb in 1 tumor but is
      contained in a region <0.3 Mb in all of the remaining amplified tumors.
      Quantitative reverse transcription-PCR (RT-PCR) of 8 genes and expressed sequence
      tags located within the core-amplified domain revealed that the HNF3alpha
      (FOXA1)(4) gene, a forkhead gene family member, was overexpressed in all of the
      amplified esophageal tumors. HNF3alpha amplification was confirmed by Southern
      blot and interphase fluorescence in situ hybridization analyses, and the results
      of real-time RT-PCR were consistent with that of the regular quantitative RT-PCR.
      Increased immunohistochemical nuclear staining of the HNF3alpha protein was
      detected in all of the tumors containing 14q13 amplification. Affymetrix
      oligonucleotide microarrays of 86 lung adenocarcinomas demonstrated that
      expression of the HNF3alpha mRNA was elevated (> or =2.5-fold of mean expression
      in normal lung) in 37% (32 of 86) of the tumors analyzed. Gene amplification of
      HNF3alpha was detected in 2 of the 5 overexpressed lung tumors examined. This is
      the first report of HNF3alpha amplification, and overexpression in esophageal and
      lung adenocarcinomas. Amplification of HNF3alpha in esophageal and lung tumors
      may suggest a potential oncogenic role for this gene in tumorigenesis.

PMID- 12234997
TI  - Mechanisms of energy restriction: effects of corticosterone on cell growth, cell
      cycle machinery, and apoptosis.
AB  - The restriction of energy intake has documented beneficial effects on numerous
      diseases including cancer, yet the mechanism(s) that accounts for these effects
      is unknown. Recently, we showed that the inhibitory activity against mammary
      carcinogenesis mediated by energy restriction (ER) is accompanied by an increase
      in the secretion of adrenal cortical steroids. However, ER caused a concomitant
      reduction in circulating levels of insulin-like growth factor-1, which also may
      be involved in inhibiting carcinogenesis. To determine what cellular and
      molecular effects may be because of corticosterone per se, detailed mechanistic
      studies were performed in vitro using a mouse mammary hyperplastic cell line
      (TM10). The following questions were addressed: (a) is corticosterone-mediated
      growth inhibition accounted for by disruption of cell cycle machinery; (b) is
      growth inhibition accompanied by the induction of apoptosis; and (c) is growth
      inhibition reversible? At doses of corticosterone (50-200 micro M for 24-72 h)
      that resulted in inhibition (up to 76%; P < 0.001) of growth, a dose- and time
      dependent G(1) arrest in cell cycle progression was observed. In the studies
      analyzing cell cycle regulatory molecules, corticosterone treatment of cells
      resulted in a strong induction (up to approximately 10-fold over control; P <
      0.01) of KIP1/P27 together with a decrease (up to 98%; P < 0.01) in cyclin
      dependent kinase 4 (CDK4) and cyclin D1 protein levels. Cells treated with
      corticosterone also showed an increased binding (up to 2.6-fold over control; P <
      0.01) of KIP1/P27 with CDK4, together with a strong decrease (up to 89%; P <
      0.01) in the kinase activity of the CDK4-cyclin D1 complex. Treatment of cells
      with KIP1/P27 antisense oligonucleotides reversed the growth inhibitory effects
      of corticosterone. Treatment of cells with RU 486, a glucocorticoid receptor
      blocker, reversed the effects of corticosterone on cell growth and KIP/P27
      protein levels suggesting the involvement of the glucocorticoid receptor in
      accounting for these effects. Additional studies assessing the biological fate of
      cells after corticosterone treatment showed that corticosterone exerted
      reversible growth inhibitory effects with limited apoptotic cell death. Together,
      these findings show a reversible cytostatic effect of corticosterone via
      perturbations in cell cycle regulators causing a G(1) arrest in the absence of
      increased levels of apoptosis. These data provide evidence for a role of
      corticosterone on some but not all of the cellular activities associated with ER
      mediated inhibition of mammary carcinogenesis.

PMID- 12234998
TI  - p53 controls global nucleotide excision repair of low levels of structurally
      diverse benzo(g)chrysene-DNA adducts in human fibroblasts.
AB  - Benzo(g)chrysene is a widespread environmental contaminant and potent carcinogen.
      We have measured the formation and nucleotide excision repair of covalent DNA
      adducts formed by the DNA-reactive metabolite of this compound in human
      fibroblasts, in which expression of the p53 tumor suppressor gene could be
      controlled by a tetracycline-inducible promoter. Cells were exposed for 1 h to
      0.01, 0.1, or 1.2 microM (+/-)-anti-benzo(g)chrysene diol-epoxide, and DNA
      adducts were assessed at various post-treatment times by subjecting isolated DNA
      to (32)P-postlabeling analysis. Four major DNA adducts were detected,
      corresponding to the reaction of either the (+)- or (-)-anti-benzo(g)chrysene
      diol-epoxide stereoisomer with adenine or guanine. Treatment with 1.2 microM
      resulted in a level of 1100 total adducts/10(8) nucleotides for both p53
      proficient and -deficient cells; removal of adducts was not observed in either
      case. In cells treated with 0.1 microM, the maximum level of total adducts at 24
      h was 150/10(8) nucleotides in p53-proficient cells and 210 adducts/10(8)
      nucleotides in p53-deficient cells. A concentration of 0.01 microM resulted in a
      maximum of 20 adducts/10(8) nucleotides in p53-proficient cells at 4 h, but 40
      adducts/10(8) nucleotides persisted in p53-deficient cells at 24 h. Whereas there
      were clear differences in the time course of adduct levels in p53-proficient
      compared with p53-deficient cells treated with 0.1 microM or 0.01 microM, these
      levels did not decrease extensively over 3 days. This is likely because of the
      stabilization of the diol-epoxide in cells, and consequent exposure and formation
      of adducts for many hours after the initial treatment. Furthermore, despite minor
      quantitative differences, all 4 of the adducts behaved similarly with respect to
      the effect of p53 expression on their removal. p53 appears to minimize the
      appearance of benzo(g)chrysene adducts in human cells by up-regulating global
      nucleotide excision repair and reducing the maximum adduct levels achieved. The
      fact that this p53-dependent effect is noted at levels of DNA adducts that are
      commonly found in human tissues (i.e., <100 adducts/10(8) nucleotides) because of
      environmental factors such as smoking is particularly significant with respect to
      human carcinogenesis related to environmental exposure.

PMID- 12234999
TI  - Alterations of p16(INK4a) and p14(ARF) in patients with severe oral epithelial
      dysplasia.
AB  - A number of genetic aberrations have been reported in end-stage squamous cell
      carcinoma of the head and neck, including p16(INK4a) and p14(ARF) (INK4a/ARF)
      inactivation rates of 70-85%. Still, the cell cycle-regulatory genes p16(INK4a)
      and p14(ARF) remain poorly understood in oral cavity premalignant lesions. This
      study evaluated INK4a/ARF locus alterations in 26 patients (28 samples) deemed to
      be at increased risk for malignant transformation to squamous cell carcinoma due
      to the diagnosis of severe oral epithelial dysplasia. Microscopically confirmed
      dysplastic oral epithelium and matching normal tissue were laser capture
      microdissected from paraffin sections, DNA was isolated, and molecular techniques
      were used to evaluate p16(INK4a) and p14(ARF) gene deletion, mutation, loss of
      heterozygosity (LOH), and hypermethylation events. Deletion of exon 1beta,
      1alpha, or 2 was detected in 3.8%, 11.5%, and 7.7% of patients, respectively.
      INK4a and ARF mutations were detected in 15.4% and 11.5% of patients with severe
      dysplasia of the oral epithelium. All identified mutations occurred in the
      INK4a/ARF conserved exon 2. Allelic imbalance was assessed using three markers
      previously reported to show high LOH rates in head and neck tumors. LOH was found
      in 42.1%, 35.0%, and 82.4% of patients for the markers IFNalpha, D9S1748, and
      D9S171, respectively. Hypermethylation of p16(INK4a) and p14(ARF) was detected in
      57.7% and 3.8% of patients, respectively, using nested, two-stage methylation
      specific PCR. The highest rates of p16(INK4a) hypermethylation occurred in
      lesions of the tongue and floor of the mouth. In addition, p16(INK4a)
      hypermethylation was significantly linked to LOH in two or more markers. These
      data support that INK4a/ARF locus alterations are frequent events preceding the
      development of oral cancer and that p16(INK4a) inactivation occurs to a greater
      extent in oral dysplasia than does p14(ARF) inactivation.

PMID- 12235000
TI  - Fully automated three-dimensional tracking of cancer cells in collagen gels:
      determination of motility phenotypes at the cellular level.
AB  - We developed a fully automated three-dimensional cell tracking system that
      quantified the effect of extracellular matrix components on the infiltration and
      migration of tumor cells. The three-dimensional trajectories of two highly
      invasive cell lines, the human HT-1080 fibrosarcoma and the human MDA-MB-231
      adenocarcinoma, were determined for long-term infiltration in plain or Matrigel
      containing collagen type I gels. We modeled the trajectories with a novel
      formulation of the continuous Markov chain model that can distinguish between the
      tendencies for infiltration or lateral motion. Parameters such as the speed of
      subpopulations, the persistence of motion in certain directions, the turning
      frequency of the cells, the ultimate direction of motion, and the cell
      distribution with the infiltration depth were obtained to quantify the migration
      and infiltration at the cellular level. Distinct migratory and infiltration
      phenotypes were identified for the two cell types that were significantly
      dependent on gel composition. The HT-1080 cell line expressed a high motility
      phenotype on the plain collagen gel surface. The Matrigel-containing gel
      significantly enhanced the infiltration and the turning frequency of the HT-1080
      cells. This study shows that tumor cell infiltration and migration are dynamic
      processes that depend significantly on the cell type and the microenvironment.

PMID- 12235001
TI  - Dissecting the oncogenic potential of Gli2: deletion of an NH(2)-terminal
      fragment alters skin tumor phenotype.
AB  - Development of basal cell carcinomas (BCCs) in skin is associated with
      uncontrolled Sonic hedgehog (Shh) signaling, which operates primarily through the
      Gli family of transcription factors. Gli2 is a mediator of physiological Shh
      signaling in skin and is sufficient to produce BCCs when overexpressed by use of
      a Keratin 5 (K5) promoter. Analysis of Gli protein deletion mutants has
      identified an NH(2)-terminal transcription repressor domain in Gli2 but not Gli1.
      To assess the potential involvement of the Gli2 repressor domain in skin tumor
      development, we overexpressed the Gli2DeltaN2 mutant in transgenic mice by use of
      the K5 promoter. K5-Gli2DeltaN2 mice developed a variety of skin tumors
      resembling human trichoblastomas, cylindromas, basaloid follicular hamartomas,
      and rarely, BCCs. In striking contrast, K5-Gli2 mice overexpressing wild-type
      Gli2 developed only BCCs. Other differences between tumors arising in these two
      sets of transgenic mice included their gross appearance, growth rate, and
      predilection for specific body sites. However, the expression levels of Shh
      target genes, which reflect the magnitude of Shh pathway activation, were not
      dramatically different. Tumors from K5-Gli2DeltaN2 mice, unlike human or mouse
      BCCs, gave rise to cell lines that constitutively expressed Shh target genes in
      vitro and were tumorigenic in nude mice. Interestingly, the phenotype of K5
      Gli2DeltaN2 mice was strikingly similar to that reported after K5 promoter-driven
      overexpression of GLI1, which lacks an NH(2)-terminal region homologous to the
      Gli2 repressor domain. These results underscore the qualitative difference in
      oncogenicity of GLI1 and Gli2 when overexpressed in skin, and reveal a previously
      unanticipated role for the Gli2 NH(2) terminus in defining tumor phenotype.

PMID- 12235002
TI  - Colony-stimulating factor-1 antisense treatment suppresses growth of human tumor
      xenografts in mice.
AB  - Matrix metalloproteinases (MMPs) foster cellular invasion by disrupting
      extracellular matrix barriers and thereby facilitate tumor development. MMPs are
      synthesized by both cancer cells and adjacent stromal cells, primarily
      macrophages. The production of macrophages is regulated by colony-stimulating
      factor-1 (CSF-1). Tissue CSF-1 expression increased significantly in embryonic
      and colon cancer xenografts. We, therefore, hypothesized that blocking CSF-1 may
      suppress tumor growth by decelerating macrophage-mediated extracellular matrix
      breakdown. Cells expressing CSF-1 and mice xenografted with CSF-1 receptor (c
      fms)- and CSF-1-negative malignant human embryonic or colon cancer cells were
      treated with mouse CSF-1 antisense oligonucleotides. Two weeks of CSF-1 antisense
      treatment selectively down-regulated CSF-1 mRNA and protein tissue expression in
      tumor lysates. CSF-1 blockade suppressed the growth of embryonic tumors to
      dormant levels and the growth of the colon carcinoma by 50%. In addition, tumor
      vascularity and the expression of MMP-2 and angiogenic factors were reduced. Six
      month survival was observed in colon carcinoma mice only after CSF-1 blockade,
      whereas controls were all dead at day 65. These results suggest that human
      embryonic and colon cancer cells up-regulate host CSF-1 and MMP-2 expression.
      Because the cancer cells used were CSF-1 negative, CSF-1 antisense targeted tumor
      stromal cell CSF-1 production. CSF-1 blockade could be a novel strategy in
      treatment of solid tumors.

PMID- 12235003
TI  - Alterations in gene expression profiles during prostate cancer progression:
      functional correlations to tumorigenicity and down-regulation of selenoprotein-P
      in mouse and human tumors.
AB  - To identify molecular changes that occur during prostate tumor progression, we
      have characterized a series of prostate cancer cell lines isolated at different
      stages of tumorigenesis from C3(1)/Tag transgenic mice. Cell lines derived from
      low- and high-grade prostatic intraepithelial neoplasia, invasive carcinoma, and
      a lung metastasis exhibited significant differences in cell growth,
      tumorigenicity, invasiveness, and angiogenesis. cDNA microarray analysis of 8700
      features revealed correlations between the tumorigenicity of the C3(1)/Tag-Pr
      cells and changes in the expression levels of genes regulating cell growth,
      angiogenesis, and invasion. Many changes observed in transcriptional regulation
      in this in vitro system are similar to those reported for human prostate cancer,
      as well as other types of human tumors. This analysis of expression patterns has
      also identified novel genes that may be involved in mechanisms of prostate
      oncogenesis or serve as potential biomarkers or therapeutic targets for prostate
      cancer. Examples include the L1-cell adhesion molecule, metastasis-associated
      gene (MTA-2), Rab-25, tumor-associated signal transducer-2 (Trop-2), and
      Selenoprotein-P, a gene that binds selenium and prevents oxidative stress. Many
      genes identified in the Pr-cell line model have been shown to be altered in human
      prostate cancer. The comprehensive microarray data provides a rational basis for
      using this model system for studies where alterations of specific genes or
      pathways are of particular interest. Quantitative real-time reverse transcription
      PCR for Selenoprotein-P demonstrated a similar down-regulation of the transcript
      of this gene in a subset of human prostate tumors, mouse tumors, and prostate
      carcinoma cell lines. This work demonstrates that expression profiling in animal
      models may lead to the identification of novel genes involved in human prostate
      cancer biology.

PMID- 12235004
TI  - Promotion of malignant astrocytoma cell migration by osteopontin expressed in the
      normal brain: differences in integrin signaling during cell adhesion to
      osteopontin versus vitronectin.
AB  - The extracellular matrix of the normal adult brain lacks expression of most of
      the adhesive glycoproteins that are known to promote cell attachment, and it has
      been thought that the malignant invasion of astrocytoma tumor is mediated
      primarily by remodeling of the matrix by the tumor cells. It has been reported,
      however, that normal brain neuropil does contain a protein(s) that promotes cell
      attachment. Therefore, we explored the possibility that the cell attachment
      protein, osteopontin, is expressed in the normal human brain. Here, we report
      that osteopontin is expressed in the cortical gray and white matter of normal
      adult brain, with the levels of osteopontin expression being equivalent to those
      in malignant astrocytic tumor biopsies as assessed by Western blot analysis.
      Immunoblotting identified osteopontin polypeptides with relative molecular
      weights of 60- and 65-kDa in normal brain white matter and in astrocytic tumors,
      with an additional 70-kDa polypeptide being identified in normal cortical gray
      matter and in some astrocytic tumors. Recombinant osteopontin was found to
      promote attachment of U-251MG human malignant astrocytoma cells in a process that
      was inhibited by anti-integrin monoclonal antibodies anti-alphavbeta3 (75%), anti
      alphavbeta5 (80%), and anti-alpha5 (40%). On attachment, integrins alphavbeta5
      and alphavbeta3 localized to focal adhesions, and there was an alteration in cell
      morphology with the formation of lamellae-like processes. The attachment was
      associated with activation of Rac in a slow and prolonged fashion and rapid
      activation of Rho. Similarly, integrins alphavbeta5 and alphavbeta3 localized to
      focal adhesions on attachment of the U-251MG cells to vitronectin, but on this
      substrate, the cells assumed a spread and flat morphology, and there was rapid
      activation of both Rac and Rho. Extracts of normal brain white matter were
      capable of promoting haptotactic migration, and this response was inhibitable by
      monoclonal antibodies anti-alphavbeta3 and anti-alpha5. Depletion of the
      osteopontin in these extracts abrogated the haptotactic response significantly
      (50%). These data indicate that the cell attachment protein, osteopontin, is
      expressed in the normal adult brain and that it has the potential to promote
      malignant astrocytoma cell invasion.

PMID- 12235005
TI  - Histidine-proline-rich glycoprotein has potent antiangiogenic activity mediated
      through the histidine-proline-rich domain.
AB  - Histidine-proline-rich glycoprotein (HPRG) is an abundant multidomain plasma
      protein evolutionarily related to high-molecular-weight kininogen. The cleaved
      form of high-molecular-weight kininogen has recently been demonstrated to exhibit
      antiangiogenic activities in vitro (J. C. Zhang et al., FASEB J., 14: 2589-2600,
      2000), mediated primarily through domain 5. HPRG contains a histidine-proline
      rich (H/P) domain with sequence and functional similarities to HKa-D5. We
      hypothesized that HPRG may also have antiangiogenic properties, localized within
      its H/P domain. The H/P domain is highly conserved among species, and because
      rabbit H/P domain is more resistant to internal proteolytic cleavage than the
      human domain, the rabbit HPRG (rbHPRG) was primarily used to assess the
      antiangiogenic activity of HPRG. Rabbit HPRG inhibited human umbilical vein
      endothelial cell (HUVEC) tube formation stimulated by fibroblast growth factor-2
      (FGF-2) or vascular endothelial growth factor on a Matrigel surface as well as
      cell proliferation of FGF-2 stimulated HUVECs. The antiangiogenic activity of
      rbHPRG was localized to the H/P domain by use of proteolytic fragments of rbHPRG
      and was further confirmed and characterized in two in vivo models of
      angiogenesis: the chorioallantoic membrane of the chick assay and the mouse
      Matrigel plug assay. Caspase-3 activation was observed in HUVECs stimulated with
      FGF-2 in the presence of rbHPRG, suggesting that apoptosis of activated
      endothelial cells may be one of the mechanisms underlying its antiangiogenic
      activity. Finally, the H/P domain of rbHPRG reduced tumor cell number when tumor
      cells were co-inoculated in the Matrigel plug assay. In conclusion, the H/P
      domain within HPRG induces the apoptosis of activated endothelial cells leading
      to potent antiangiogenic effects.

PMID- 12235006
TI  - The desmoplastic response to infiltrating breast carcinoma: gene expression at
      the site of primary invasion and implications for comparisons between tumor
      types.
AB  - The gene expression patterns of desmoplasia are becoming exposed through the
      application of global gene expression technologies such as cDNA microarrays or
      serial analysis of gene expression (SAGE). These patterns represent the sum of
      the many cellular components of the host stromal response to an infiltrating
      carcinoma. In studies of human neoplasms, it would be useful to identify those
      prototypical genes that characteristically indicate the recognizable forms of the
      responses to individual tumor types. Such genes may offer clues to better
      understand the process of invasion itself, the interactions between tumor and
      host cells, and tumor-specific differences in invasion. We used SAGE-defined
      genes and in situ transcript labeling to characterize the desmoplastic stroma
      induced by infiltrating ductal carcinomas of the breast. Principal component
      analysis identified 103 SAGE tags as specific for invasive breast carcinomas, in
      comparison with in situ duct carcinomas or normal breast epithelium. Of these, 68
      tags corresponded to known genes. Six of the 68 genes from this breast cancer
      "invasion-specific" cluster were further characterized by in situ hybridization
      to breast cancer tissues. Results of in situ hybridization demonstrated that each
      gene was expressed within one of five distinct regions of the invasive tumors
      (neoplastic epithelium; angioendothelium; inflammatory, panstromal, and
      juxtatumoral stroma), reflecting a defined architectural structure to the
      transcriptome of invasive breast cancers. Two of these 6 genes were specifically
      expressed by the stromal cells within the invasive carcinoma; however, 1
      (collagen 1alpha1) was expressed throughout the stromal response (panstromal
      expression), whereas the second (osteonectin) was specifically expressed within
      the juxtatumoral stromal cells, indicating a critical "regionality" of gene
      expression within the stromal response itself. A comparison of the gene
      expression profiles of the juxtatumoral stroma in breast and pancreatic
      carcinomas indicated important differences between the two, suggesting tumor
      specific or organ-specific differences in the desmoplastic responses. Some of the
      genes presented are novel markers of the invasive process, imply communication at
      the host/tumor interface, and suggest potential therapeutic targets.

PMID- 12235007
TI  - Periostin secreted by epithelial ovarian carcinoma is a ligand for
      alpha(V)beta(3) and alpha(V)beta(5) integrins and promotes cell motility.
AB  - Periostin (PN) is a secreted protein that shares a structural homology to the
      axon guidance protein fasciclin I in insects. Previously, we reported that PN
      expression is up-regulated in epithelial ovarian tumors. We further examined the
      role of PN in ovarian cancer. PN is expressed in several normal tissues but not
      in normal ovaries and has a tendency for higher expression in fetal tissues.
      Ovarian cancer cells secrete PN, which can accumulate in malignant ascites of
      ovarian cancer patients. Purified recombinant PN supports adhesion of ovarian
      epithelial cells that can be inhibited by monoclonal antibodies against
      alpha(V)beta(3) or alpha(V)beta(5) integrin, but not by anti-beta(1) integrin
      antibody. Furthermore, alpha(V)beta(3) integrin, but not beta(1) integrins,
      colocalizes to the focal adhesion plaques formed on PN. Cells plated on PN form
      fewer stress fibers and are more motile compared with those plated on
      fibronectin. We propose PN functions as a ligand for alpha(V)beta(3) and
      alpha(V)beta(5) integrins to support adhesion and migration of ovarian epithelial
      cells.

PMID- 12235008
TI  - Raloxifene, a mixed estrogen agonist/antagonist, induces apoptosis in androgen
      independent human prostate cancer cell lines.
AB  - Raloxifene, a selective estrogen receptor (ER) modulator, is a mixed estrogen
      agonist/antagonist that has been shown to prevent osteoporosis and breast cancer
      in women. Because the prostate contains high levels of ER-beta, the present study
      investigated the effect of raloxifene in three well-characterized, androgen
      independent human prostate cancer cell lines: (a) PC3; (b) PC3M; and (c) DU145.
      Reverse transcriptase-PCR and Western blot analysis for ER-alpha and ER-beta
      demonstrated that all three cell lines express ER-beta, whereas only PC3 and PC3M
      cells were positive for ER-alpha. After the treatment with raloxifene, a dramatic
      increase in cell death was observed in a dose-dependent manner in the three
      prostate cancer cell lines (10(-9) to 10(-6) M range). Because the three prostate
      cancer cell lines demonstrated similar morphological changes after the raloxifene
      treatment, PC3 (ER-alpha/ER-beta+) and DU145 (ER-beta+ only) cells were selected
      to further characterize the raloxifene-induced cell death. Using the nucleus
      specific stain 4',6-diamidino-2-phenylindole, nuclear fragmentation was observed
      in a time-dependent manner in both cell lines after exposure to 10(-6) M
      raloxifene. Using the terminal deoxynucleotidyl transferase-mediated nick end
      labeling apoptotic assay, it was demonstrated that the nuclear fragmentation was
      caused by apoptosis. To investigate the possibility that caspase activation is
      involved in raloxifene-induced apoptosis, cells were treated with the pan-caspase
      inhibitor ZVAD. The results demonstrated that the dramatic change in cellular
      morphology after treatment with raloxifene was no longer observed when cells were
      pretreated with ZVAD. Immunoblot demonstrated activation of caspases 8 and 9 in
      PC3 and DU145 cells, respectively. Taken together, these results demonstrate that
      the mixed estrogen agonist/antagonist, raloxifene, induces apoptosis in androgen
      independent human prostate cancer cell lines.

PMID- 12235009
TI  - Metallothionein promotes laminin-1-induced acinar differentiation in vitro and
      reduces tumor growth in vivo.
AB  - Laminin-1 was found previously to promote the morphological differentiation of a
      salivary gland cell line (HSG) into acinar-like structures with polarized nuclei
      (1). Here, microarray analysis showed that laminin-1 induced mainly one gene
      family of proteins, the metal binding metallothioneins (MTs), out of more than
      10,500 cDNAs screened. Northern and protein analyses demonstrated that MT was
      increased some 5-10-fold by laminin-1 as early as 6 h after incubation. Cells
      transfected with this gene formed 3-5-fold larger acinar-like structures on
      exposure to laminin-1 in vitro and smaller, more differentiated tumors in vivo.
      We conclude that MTs are important in acinar cell morphological differentiation
      and may have novel functions other than metal binding.

PMID- 12235010
TI  - Identifying microcalcifications in benign and malignant breast lesions by probing
      differences in their chemical composition using Raman spectroscopy.
AB  - We have applied Raman spectroscopy to analyze the chemical composition of
      microcalcifications occurring in benign and malignant lesions in the human
      breast. Microcalcifications were initially separated into two categories based on
      their Raman spectrum: type I, calcium oxalate dihydrate, and type II, calcium
      hydroxyapatite. Type I microcalcifications were diagnosed as benign, whereas type
      II were subdivided into benign and malignant categories using principal component
      analysis, a statistical technique. Although type II microcalcifications are
      primarily composed of calcium hydroxyapatite, they also contain trace amounts of
      several biological impurities. Using principal component analysis, we were able
      to highlight subtle chemical differences in type II microcalcifications that
      correlate with breast disease. On the basis of these results, we believe that
      type II microcalcifications formed in benign ducts typically contain a larger
      amount of calcium carbonate and a smaller amount of protein than those formed in
      malignant ducts. Using this diagnostic strategy, we were able to distinguish
      microcalcifications occurring in benign and malignant ducts with a sensitivity of
      88% and a specificity of 93%. This is a significant improvement over current X
      ray mammography techniques, which are unable to reliably differentiate
      microcalcifications in benign and malignant breast lesions.

PMID- 12235012
TI  - Lung edema clearance: 20 years of progress.

PMID- 12235011
TI  - Significance of blood vessel leakiness in cancer.
AB  - Despite major advances in the field of tumor angiogenesis, relatively little
      attention has been paid to the permeability of blood vessels in tumors. The
      leakiness of tumor vessels is well documented in experimental tumor models and in
      human cancer, but the mechanism is poorly understood, as are the implications to
      the rate of cancer growth, predisposition to metastasis, and delivery of
      macromolecular therapeutics to tumor cells. Sixteen experts in the fields of
      cancer biology and vascular biology gathered at the William Guy Forbeck "Focus on
      the Future" Conference to discuss this topic. The meeting was the first of its
      kind focused on the significance of blood vessel leakiness in tumors. The
      participants discussed the cellular basis of tumor vessel leakiness, endothelial
      barrier function of blood vessels, monitoring tumor vessel leakiness, mediators
      of endothelial leakiness, consequences of tumor vessel leakiness, genomic
      analysis of vascular targets, targeting drugs to tumor vessels, and therapeutic
      manipulation of tumor vessels. The group concluded that a more complete
      understanding of the basic biology of tumor vessels will be necessary to fully
      appreciate the consequences of vessel leakiness in cancer. New research tools
      such as intravital measurements of tumor blood flow and vessel leakiness, in vivo
      phage display, magnetic resonance imaging, and use of selective angiogenesis
      inhibitors will contribute to this understanding.

PMID- 12235013
TI  - Intramuscular triacylglycerol utilization in human skeletal muscle during
      exercise: is there a controversy?
AB  - Intramuscular triacylglyerols (IMTGs) represent a potentially important energy
      source for contracting human skeletal muscle. Although the majority of evidence
      from isotope tracer and (1)H-magnetic resonance spectroscopy (MRS) studies
      demonstrate IMTG utilization during exercise, controversy regarding the
      importance of IMTG as a metabolic substrate persists. The controversy stems from
      studies that measure IMTG in skeletal muscle biopsy samples and report no
      significant net IMTG degradation during prolonged moderate-intensity (55-70%
      maximal O(2) consumption) exercise lasting 90-120 min. Although postexercise
      decrements in IMTG levels are often reported from direct muscle measurements, the
      marked between-biopsy variability (approximately 23%) that has been reported with
      this technique in untrained subjects is larger than the expected decrease in IMTG
      content, effectively precluding significant findings. In contrast, recent data
      obtained in endurance-trained subjects demonstrated reduced variability between
      duplicate biopsies (approximately 12%), and significant changes in IMTG were
      detected after 120 min of moderate-intensity exercise. Therefore, it is our
      contention that the muscle biopsy, isotope tracer, and (1)H-MRS techniques report
      significant and energetically important oxidation of free fatty acids derived
      from IMTGs during prolonged moderate exercise.

PMID- 12235014
TI  - Assessment of respiratory mechanics in small animals: the simpler the better?

PMID- 12235015
TI  - A reevaluation of the validity of unrestrained plethysmography in mice.
AB  - Presently, unrestrained plethysmography is widely used to assess bronchial
      responsiveness in mice. An empirical quantity known as enhanced pause is derived
      from the plethysmographic box pressure [P(b)(t), where t is time] and assumed to
      be an index of bronchoconstriction. We show that P(b)(t) is determined largely by
      gas conditioning when normal mice breathe spontaneously inside a closed chamber
      in which the air is at ambient conditions. When the air in the chamber is heated
      and humidified to body conditions, the changes in P(b)(t) are reduced by about
      two-thirds. The remaining changes are thus due to gas compression and expansion
      within the lung and are amplified when the animals breathe through increased
      resistances. We show that the time integral of P(b)(t) over inspiration is
      accurately predicted by a term containing airway resistance, functional residual
      capacity, and tidal volume. We conclude that unrestrained plethysmography can be
      used to accurately characterize changes in airway resistance only if functional
      residual capacity and tidal volume are measured independently and the chamber gas
      is preconditioned to body temperature and humidity.

PMID- 12235016
TI  - Noninvasive measurement of midexpiratory flow indicates bronchoconstriction in
      allergic rats.
AB  - This study was designed to evaluate the value and applicability of tidal
      breathing pattern analysis to assess bronchoconstriction in conscious rats. Using
      noninvasive, head-out body plethysmography and the decrease in tidal
      midexpiratory flow (EF(50)), we measured airway responsiveness (AR) to inhaled
      acetylcholine and allergen in conscious Brown-Norway rats, followed by invasive
      determination of pulmonary conductance (GL) and EF(50) in anesthetized rats. Dose
      response studies to acetylcholine showed that noninvasively recorded EF(50)
      closely reflected the dose-dependent decreases observed with the invasive
      monitoring of simultaneously measured GL and EF(50). After sensitization and
      intratracheal boost to ovalbumin or saline, rats were assessed for early and late
      AR to aerosolized ovalbumin. Ovalbumin aerosol challenge resulted in early and
      late AR in allergen-sensitized rats, whereas controls were unresponsive. The
      allergen-specific AR, as measured noninvasively by EF(50), was similar in degree
      compared with invasively recorded EF(50) and GL and was associated with enhanced
      IgE and airway inflammation. We conclude that EF(50) is a noninvasive and
      physiologically valid index of bronchoconstriction in a rat model of asthma.

PMID- 12235017
TI  - Bradykinin does not mediate cutaneous active vasodilation during heat stress in
      humans.
AB  - To test the hypothesis that bradykinin effects cutaneous active vasodilation
      during hyperthermia, we examined whether the increase in skin blood flow (SkBF)
      during heat stress was affected by blockade of bradykinin B(2) receptors with the
      receptor antagonist HOE-140. Two adjacent sites on the forearm were instrumented
      with intradermal microdialysis probes for local delivery of drugs in eight
      healthy subjects. HOE-140 was dissolved in Ringer solution (40 microM) and
      perfused at one site, whereas the second site was perfused with Ringer alone.
      SkBF was monitored by laser-Doppler flowmetry (LDF) at both sites. Mean arterial
      pressure (MAP) was monitored from a finger, and cutaneous vascular conductance
      (CVC) was calculated (CVC = LDF/MAP). Water-perfused suits were used to control
      body temperature and evoke hyperthermia. After hyperthermia, both microdialysis
      sites were perfused with 28 mM nitroprusside to effect maximal vasodilation.
      During hyperthermia, CVC increased at HOE-140 (69 +/- 2% maximal CVC, P < 0.01)
      and untreated sites (65 +/- 2% maximal CVC, P < 0.01). These responses did not
      differ between sites (P > 0.05). Because the bradykinin B(2)-receptor antagonist
      HOE-140 did not alter SkBF responses to heat stress, we conclude that bradykinin
      does not mediate cutaneous active vasodilation.

PMID- 12235018
TI  - Cardiopulmonary resuscitation in the mouse.
AB  - We sought to develop a model of cardiac arrest and resuscitation on mice that
      would be comparable to that of large mammals and would allow for more fundamental
      investigations on cardiopulmonary arrest and cardiac resuscitation. A model of
      cardiopulmonary resuscitation previously developed by our group on rats was
      adapted to anesthetized, mechanically ventilated adult male Institute of Cancer
      Research mice that weighed 46 +/- 3 g. The trachea was intubated through the
      mouth, and end-tidal PCO(2) (PET(CO(2))) was measured with a microcapnometer.
      Catheters were advanced into the aorta and into the right atrium, and coronary
      perfusion pressure (CPP) was computed. A 1.5-mA alternating current was delivered
      to the right ventricular endocardium, which produced ventricular fibrillation or
      a pulseless rhythm. Precordial compression was begun 4 min later. Ten sequential
      studies were performed, during which five animals were successfully resuscitated
      and five failed resuscitation efforts. Successful resuscitation was contingent on
      the restoration of threshold levels of CPP and PET(CO(2)) during chest
      compression. As in rats, swine, and human patients, threshold levels of mean
      aortic pressure, CPP, and PET(CO(2)) were critical determinates of
      resuscitability in this murine model of threshold level of cardiac arrest and
      resuscitation.

PMID- 12235019
TI  - Exercise endurance 1, 3, and 6 h after caffeine ingestion in caffeine users and
      nonusers.
AB  - The purpose of the present study was to examine the duration of caffeine's
      ergogenic effect and whether it differs between users and nonusers of the drug.
      Twenty-one subjects (13 caffeine users and 8 nonusers) completed six randomized
      exercise rides to exhaustion at 80% of maximal oxygen consumption after ingesting
      either a placebo or 5 mg/kg of caffeine. Exercise to exhaustion was completed
      once per week at either 1, 3, or 6 h after placebo or drug ingestion. Exercise
      time to exhaustion differed between users and nonusers with the ergogenic effect
      being greater and lasting longer in nonusers. For the nonusers, exercise times 1,
      3, and 6 h after caffeine ingestion were 32.7 +/- 8.4, 32.1 +/- 8.6, and 31.7 +/-
      12.0 min, respectively, and these values were each significantly greater than the
      corresponding placebo values of 24.2 +/- 6.4, 25.8 +/- 9.0, and 23.2 +/- 7.1 min.
      For caffeine users, exercise times 1, 3, and 6 h after caffeine ingestion were
      27.4 +/- 7.2, 28.1 +/- 7.8, and 24.5 +/- 7.6 min, respectively. Only exercise
      times 1 and 3 h after drug ingestion were significantly greater than the
      respective placebo trials of 23.3 +/- 6.5, 23.2 +/- 7.1, and 23.5 +/- 5.7 min. In
      conclusion, both the duration and magnitude of the ergogenic effect that followed
      a 5 mg/kg dose of caffeine were greater in the nonusers compared with the users.

PMID- 12235020
TI  - Dysanaptic growth of conducting airways after pneumonectomy assessed by CT scan.
AB  - In immature dogs after pneumonectomy (PNX), pulmonary viscous resistance is
      persistently elevated predominantly as a result of a high airway resistance
      (Raw). We examined the anatomical basis for this observation by using
      computerized tomography scans obtained from foxhounds 4-10 mo after right PNX.
      Airways of the left lower lobe were followed from generations z = 0 (trachea) to
      z = 12. By 4 mo post-PNX, airway length increased significantly relative to sham
      operated dogs, but airway cross-sectional area (CSA) did not. By 10 mo post-PNX,
      average airway CSA was 24% above that in controls. Theoretically, the increased
      airway length and CSA should reduce lobar Raw by 50%. However, post-PNX airway
      dilatation did not normalize total CSA, and estimated resistance due to
      turbulence and convective acceleration increased threefold; i.e., the 50%
      reduction in lobar Raw would be offset by the loss of four of seven lobes. Thus
      the expected reduction in work of breathing in the whole animal is only ~30%,
      consistent with previously measured work of breathing in pneumonectomized dogs.
      We conclude that airway structure adapts slowly and incompletely, resulting in
      limited functional compensation.

PMID- 12235021
TI  - Cutaneous vascular function during acute hyperglycemia in healthy young adults.
AB  - Although it is well established that severe chronic hyperglycemia is associated
      with microvascular disease, it is not known whether transient hyperglycemia
      similar to that observed with impaired glucose tolerance or early Type 2 diabetes
      contributes to this pathology by altering microvascular function. To test the
      hypothesis that acute hyperglycemia decreases microvascular vasodilator
      responsiveness in human skin, we measured the cutaneous vasodilator response to
      local warming. This response can be divided into two phases, an initial peak that
      relies predominantly on local sensory nerves and a second slower phase that is
      largely dependent on endothelial nitric oxide. We reasoned that a change in one
      or both phases would indicate a change in the corresponding mechanism(s) with
      hyperglycemia. Twenty-eight healthy volunteers (14 women, 14 men) were randomly
      divided into three groups, corresponding to 6 h of euglycemia (n = 8), 6 h when
      glucose was clamped at approximately 7 mmol/l (n = 10), or 6 h when glucose was
      varied to mimic a postprandial pattern (i.e., peak glucose approximately 11.1
      mmol/l) commonly observed in individuals with impaired glucose tolerance (n =
      10). Insulin concentrations in all instances were maintained at approximately 65
      pmol/l by means of continuous infusions of somatostatin and insulin. Glucagon and
      growth hormone were also continuously infused to maintain their basal
      concentrations. Despite substantial differences in both the level and pattern of
      glucose concentrations, neither maximum cutaneous vasodilation nor the pattern of
      the vasodilator response to local warming differed over the 6 h of study. We
      conclude that acute hyperglycemia similar to levels commonly observed in people
      with either early Type 2 diabetes or impaired glucose tolerance does not alter
      the vasodilator response to local warming of the skin in humans.

PMID- 12235022
TI  - Glutamate ingestion and its effects at rest and during exercise in humans.
AB  - Glutamate is central to several transamination reactions that affect the
      production of ammonia, alanine, glutamine, as well as TCA cycle intermediates
      during exercise. To further study glutamate metabolism, we administered 150 mg/kg
      body wt of monosodium glutamate (MSG) and placebo to seven male subjects who then
      either rested or exercised (15-min cycling at approximately 85% maximal oxygen
      consumption). MSG ingestion resulted in elevated plasma glutamate, aspartate, and
      taurine, both at rest and during exercise (P < 0.05), whereas most other amino
      acids were unchanged. Neither plasma alanine nor ammonia was altered at rest.
      During exercise and after glutamate ingestion, alanine was increased (P < 0.05)
      and ammonia was attenuated (P < 0.05). Glutamine was also elevated after
      glutamate ingestion during rest and exercise trials. MSG administration also
      resulted in elevated insulin levels (P < 0.05), which were parallel to the trend
      in C-peptide levels. Thus MSG can successfully elevate plasma glutamate, both at
      rest and during exercise. The plasma amino acid responses suggest that increased
      glutamate availability during exercise alters its distribution in transamination
      reactions within active muscle, which results in elevated alanine and decreased
      ammonia levels.

PMID- 12235023
TI  - Vestibulosympathetic reflex during mental stress.
AB  - Increases in sympathetic neural activity occur independently with either
      vestibular or mental stimulation, but it is unknown whether sympathetic
      activation is additive or inhibitive when both stressors are combined. The
      purpose of the present study was to investigate the combined effects of
      vestibular and mental stimulation on sympathetic neural activation and arterial
      pressure in humans. Muscle sympathetic nerve activity (MSNA), arterial pressure,
      and heart rate were recorded in 10 healthy volunteers in the prone position
      during 1) head-down rotation (HDR), 2) mental stress (MS; using arithmetic), and
      3) combined HDR and MS. HDR significantly (P < 0.05) increased MSNA (9 +/- 2 to
      13 +/- 2 bursts/min). MS significantly increased MSNA (8 +/- 2 to 13 +/- 2
      bursts/min) and mean arterial pressure (87 +/- 2 to 101 +/- 2 mmHg). Combined HDR
      and MS significantly increased MSNA (9 +/- 1 to 16 +/- 2 bursts/min) and mean
      arterial pressure (89 +/- 2 to 100 +/- 3 mmHg). Increases in MSNA (7 +/- 1
      bursts/min) during the combination trial were not different from the algebraic
      sum of each trial performed alone (8 +/- 2 bursts/min). We conclude that the
      interaction for MSNA and arterial pressure is additive during combined vestibular
      and mental stimulation. Therefore, vestibular- and stress-mediated increases of
      MSNA appear to occur independently in humans.

PMID- 12235024
TI  - Determinants of maximal O(2) uptake in rats selectively bred for endurance
      running capacity.
AB  - O(2) transport during maximal exercise was studied in rats bred for extremes of
      exercise endurance, to determine whether maximal O(2) uptake (VO(2 max)) was
      different in high- (HCR) and low-capacity runners (LCR) and, if so, which were
      the phenotypes responsible for the difference. VO(2 max) was determined in five
      HCR and six LCR female rats by use of a progressive treadmill exercise protocol
      at inspired PO(2) of approximately 145 (normoxia) and approximately 70 Torr
      (hypoxia). Normoxic VO(2 max) (in ml. min(-1). kg(-1)) was 64.4 +/- 0.4 and 57.6
      +/- 1.5 (P < 0.05), whereas VO(2 max) in hypoxia was 42.7 +/- 0.8 and 35.3 +/-
      1.5 (P < 0.05) in HCR and LCR, respectively. Lack of significant differences
      between HCR and LCR in alveolar ventilation, alveolar-to-arterial PO(2)
      difference, or lung O(2) diffusing capacity indicated that neither ventilation
      nor efficacy of gas exchange contributed to the difference in VO(2 max) between
      groups. Maximal rate of blood O(2) convection (cardiac output times arterial
      blood O(2) content) was also similar in both groups. The major difference
      observed was in capillary-to-tissue O(2) transfer: both the O(2) extraction ratio
      (0.81 +/- 0.002 in HCR, 0.74 +/- 0.009 in LCR, P < 0.001) and the tissue
      diffusion capacity (1.18 +/- 0.09 in HCR and 0.92 +/- 0.05 ml. min(-1). kg(-1).
      Torr(-1) in LCR, P < 0.01) were significantly higher in HCR. The data indicate
      that selective breeding for exercise endurance resulted in higher VO(2 max)
      mostly associated with a higher transfer of O(2) at the tissue level.

PMID- 12235025
TI  - Influence of head position on thermal stress in newborns: simulation using a
      thermal mannequin.
AB  - The influence of head position on thermal stress was assessed by using a heavily
      clothed thermal mannequin in three different body positions [supine, face
      straight up (FSU); supine, face to the side (FTS); prone, FTS] and with or
      without the head covered by a bonnet. The mannequin was exposed to air
      temperatures of 29, 32, 34, and 36 degrees C. When the head is uncovered, body or
      head position has no impact on heat loss. When the head is covered, dry heat loss
      from the mannequin as a whole (and that from the head in particular) is lower (
      0.35 to -0.40 W) in the FTS position than in the FSU position as a result of
      decreased heat loss from the surface area of the face in contact with the
      mattress. In the FTS position and with the head covered, there was no difference
      in heat loss between the prone and supine positions. The results suggest that in
      heavily clothed newborns whose head is covered by a bonnet, thermal stress
      depends on the head position.

PMID- 12235026
TI  - Break point of serum creatine kinase release after endurance exercise.
AB  - We investigated whether there is a break point of creatine kinase (CK) release
      after daily endurance exercise and whether CK response depends on individual
      physical characteristics. Fifteen healthy young men performed 90 min of bicycle
      exercise for 3 consecutive days. Body composition, properties of the quadriceps
      femoris muscle (QFM), and aerobic and anaerobic capacities were estimated before
      the test. Blood samples were obtained 22 times during the experimental period.
      Endurance exercise significantly elevated serum CK from 3 h after the first
      exercise session (P < 0.05) and gradually increased thereafter. Subjects were
      classified into two groups according to their peak CK values: high responders
      (HR; >500 IU/l of CK) and low responders (LR; <300 IU/l of CK). Peak CK values
      during the experimental period correlated (P < 0.01) with workload/cross
      sectional area of the QFM (r = 0.658), workload/volume of the QFM (r = 0.648),
      and knee extensor strength/body mass (r = -0.634); however, the HR and LR groups
      were separated in each variable. Thus the break point of CK release after
      endurance exercise under these conditions is 300-500 IU/l, two or three times
      higher than in the resting condition, and is associated with properties of the
      QFM.

PMID- 12235027
TI  - Comparative responses to alpha,beta-methylene-ATP in cat pulmonary, mesenteric,
      and hindquarter vascular beds.
AB  - Responses to the P2X-purinoceptor agonist alpha,beta-methylene-ATP (alpha,beta
      MeATP) were investigated in the pulmonary, hindquarter, and mesenteric vascular
      beds in the cat. Under constant-flow conditions, injections of alpha,beta-MeATP
      caused dose-related increases in perfusion pressure in the pulmonary and
      hindquarter beds and a biphasic response in the mesenteric circulation. In the
      pulmonary vascular bed, the order of potency was alpha,beta-MeATP > U-46619 >
      angiotensin II, whereas, in the hindquarters, the order of potency was
      angiotensin II > U-46619 > alpha,beta-MeATP. The order of potency was similar in
      the hindquarter and mesenteric beds when the pressor component of the response to
      alpha,beta-MeATP was compared with responses to angiotensin II and U-46619. The
      P2X-receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid
      attenuated the pressor response to alpha,beta-MeATP in the hindquarter
      circulation and the pressor component in the mesenteric vascular bed. Pressor
      responses to alpha,beta-MeATP were not altered by cyclooxygenase, alpha
      adrenergic, or angiotensin AT(1) antagonists. These data show that alpha,beta
      MeATP has potent pressor activity in the pulmonary circulation, where it was 100
      fold more potent than angiotensin II. In contrast, alpha,beta-MeATP had modest
      pressor activity in the systemic bed, where it was 1,000-fold less potent than
      angiotensin II. These data suggest that responses to alpha,beta-MeATP are
      dependent on the vascular bed studied and may be dependent on the density of P2X
      receptors in the vascular bed.

PMID- 12235028
TI  - Decreased airway narrowing and smooth muscle contraction in hyperresponsive pigs.
AB  - Increased smooth muscle contractility or reduced smooth muscle mechanical loads
      could account for the excessive airway narrowing and hyperresponsiveness seen in
      asthma. These mechanisms were investigated by using an allergen-induced porcine
      model of airway hyperresponsiveness. Airway narrowing to electric field
      stimulation was measured in isolated bronchial segments, over a range of
      transmural pressures (0-20 cmH(2)O). Contractile responses to ACh were measured
      in bronchial segments and in isolated tracheal smooth muscle strips isolated from
      control and test (ovalbumin sensitized and challenged) pigs. Test airways
      narrowed less than controls (P < 0.0001). Test pigs showed reduced contractility
      to ACh, both in isolated bronchi (P < 0.01) and smooth muscle strips (P < 0.01).
      Thus isolated airways from pigs exhibiting airway hyperresponsiveness in vivo are
      hyporesponsive in vitro. The decreased narrowing in bronchi from hyperresponsive
      pigs may be related to decreased smooth muscle contractility. These data suggest
      that mechanisms external to the airway wall may be important to the
      hyperresponsive nature of sensitized lungs.

PMID- 12235029
TI  - Intensity-controlled treadmill running in mice: cardiac and skeletal muscle
      hypertrophy.
AB  - Whereas novel pathways of pathological heart enlargement have been unveiled by
      thoracic aorta constriction in genetically modified mice, the molecular
      mechanisms of adaptive cardiac hypertrophy remain virtually unexplored and call
      for an effective and well-characterized model of physiological mechanical
      loading. Experimental procedures of maximal oxygen consumption (VO(2 max)) and
      intensity-controlled treadmill running were established in 40 female and 36 male
      C57BL/6J mice. An inclination-dependent VO(2 max) with 0.98 test-retest
      correlation was found at 25 degrees treadmill grade. Running for 2 h/day, 5
      days/wk, in intervals of 8 min at 85-90% of VO(2 max) and 2 min at 50% (adjusted
      to weekly VO(2 max) testing) increased VO(2 max) to a plateau 49% above sedentary
      females and 29% in males. Running economy improved in both sexes, and
      echocardiography indicated significantly increased left ventricle posterior wall
      thickness. Ventricular weights increased by 19-29 and 12-17% in females and
      males, respectively, whereas cardiomyocyte dimensions increased by 20-32, and 17
      23% in females and males, respectively; skeletal muscle mass increased by 12-18%.
      Thus the model mimics human responses to exercise and can be used in future
      studies of molecular mechanisms underlying these adaptations.

PMID- 12235031
TI  - Increased rate of force development and neural drive of human skeletal muscle
      following resistance training.
AB  - The maximal rate of rise in muscle force [rate of force development (RFD)] has
      important functional consequences as it determines the force that can be
      generated in the early phase of muscle contraction (0-200 ms). The present study
      examined the effect of resistance training on contractile RFD and efferent motor
      outflow ("neural drive") during maximal muscle contraction. Contractile RFD
      (slope of force-time curve), impulse (time-integrated force), electromyography
      (EMG) signal amplitude (mean average voltage), and rate of EMG rise (slope of EMG
      time curve) were determined (1-kHz sampling rate) during maximal isometric muscle
      contraction (quadriceps femoris) in 15 male subjects before and after 14 wk of
      heavy-resistance strength training (38 sessions). Maximal isometric muscle
      strength [maximal voluntary contraction (MVC)] increased from 291.1 +/- 9.8 to
      339.0 +/- 10.2 N. m after training. Contractile RFD determined within time
      intervals of 30, 50, 100, and 200 ms relative to onset of contraction increased
      from 1,601 +/- 117 to 2,020 +/- 119 (P < 0.05), 1,802 +/- 121 to 2,201 +/- 106 (P
      < 0.01), 1,543 +/- 83 to 1,806 +/- 69 (P < 0.01), and 1,141 +/- 45 to 1,363 +/-
      44 N. m. s(-1) (P < 0.01), respectively. Corresponding increases were observed in
      contractile impulse (P < 0.01-0.05). When normalized relative to MVC, contractile
      RFD increased 15% after training (at zero to one-sixth MVC; P < 0.05).
      Furthermore, muscle EMG increased (P < 0.01-0.05) 22-143% (mean average voltage)
      and 41-106% (rate of EMG rise) in the early contraction phase (0-200 ms). In
      conclusion, increases in explosive muscle strength (contractile RFD and impulse)
      were observed after heavy-resistance strength training. These findings could be
      explained by an enhanced neural drive, as evidenced by marked increases in EMG
      signal amplitude and rate of EMG rise in the early phase of muscle contraction.

PMID- 12235030
TI  - Effects of sprint training on contractility and [Ca(2+)](i) transients in adult
      rat myocytes.
AB  - The effects of 6-8 wk of high-intensity sprint training (HIST) on rat myocyte
      contractility and intracellular Ca(2+) concentration ([Ca(2+)](i)) transients
      were investigated. Compared with sedentary (Sed) myocytes, HIST induced a modest
      (5%) but significant (P < 0.0005) increase in cell length with no changes in cell
      width. In addition, the percentage of myosin heavy chain alpha-isoenzyme
      increased significantly (P < 0.02) from 0.566 +/- 0.077% in Sed rats to 0.871 +/-
      0.006% in HIST rats. At all three (0.6, 1.8, and 5 mM) extracellular Ca(2+)
      concentrations ([Ca(2+)](o)) examined, maximal shortening amplitudes and maximal
      shortening velocities were significantly (P < 0.0001) lower and half-times of
      relaxation were significantly (P < 0.005) longer in HIST myocytes. HIST myocytes
      had significantly (P < 0.0001) higher diastolic [Ca(2+)](i) levels. Compared with
      Sed myocytes, systolic [Ca(2+)](i) levels in HIST myocytes were higher at 0.6 mM
      [Ca(2+)](o), similar at 1.8 mM [Ca(2+)](o), and lower at 5 mM [Ca(2+)](o). The
      amplitudes of [Ca(2+)](i) transients were significantly (P < 0.0001) lower in
      HIST myocytes. Half-times of [Ca(2+)](i) transient decline, an estimate of
      sarcoplasmic reticulum (SR) Ca(2+) uptake activity, were not different between
      Sed and HIST myocytes. Compared with Sed hearts, Western blots demonstrated a
      significant (P < 0.03) threefold decrease in Na(+)/Ca(2+) exchanger, but SR
      Ca(2+)-ATPase and calsequestrin protein levels were unchanged in HIST hearts. We
      conclude that HIST effected diminished myocyte contractile function and
      [Ca(2+)](i) transient amplitudes under the conditions studied. We speculate that
      downregulation of Na(+)/Ca(2+) exchanger may partly account for the decreased
      contractility in HIST myocytes.

PMID- 12235032
TI  - Rate of NO scavenging alters effects of recombinant hemoglobin solutions on
      pulmonary vasoreactivity.
AB  - Many hemoglobin-based oxygen carriers (HBOCs) produce systemic and pulmonary
      hypertension and may increase microvascular permeability as a consequence of
      nitric oxide (NO) scavenging. In this study, we examined the effects of two
      recombinant human hemoglobin solutions, rHb1.1 and rHb2.0 for injection (rHb2.0),
      with different rates of NO scavenging on vasoconstrictor reactivity and vascular
      permeability in isolated, saline-perfused rat lungs. We hypothesized that rHb1.1,
      a first-generation HBOC with an NO scavenging rate similar to that of native
      human hemoglobin, would exacerbate pulmonary vasoconstriction and permeability
      and that rHb2.0, a second-generation HBOC with an NO scavenging rate
      approximately 20- to 30-fold lower than that of rHb1.1, would minimally influence
      these responses. Consistent with this hypothesis, rHb1.1 enhanced pulmonary
      vasoconstrictor reactivity to both hypoxia and thromboxane mimetic U-46619 in a
      dose-dependent fashion. In contrast, rHb2.0 produced little or no change in
      reactivity to these stimuli. Furthermore, whereas rHb1.1 abrogated pulmonary
      vasodilation to the NO-donor S-nitroso-N-acetyl-penicillamine (SNAP), dose
      dependent responses to SNAP were preserved, albeit attenuated, in lungs treated
      with rHb2.0. Finally, the capillary filtration coefficient was unaltered by
      either rHb1.1 or rHb2.0. We conclude that pulmonary hemodynamic responses to
      rHb2.0 are greatly reduced compared with those observed with rHb1.1, consistent
      with rHb2.0 having a diminished capacity to scavenge NO. In addition, neither
      hemoglobin solution measurably altered microvascular permeability in this
      preparation.

PMID- 12235033
TI  - Early postexercise muscle glycogen recovery is enhanced with a carbohydrate
      protein supplement.
AB  - In the present study, we tested the hypothesis that a carbohydrate-protein (CHO
      Pro) supplement would be more effective in the replenishment of muscle glycogen
      after exercise compared with a carbohydrate supplement of equal carbohydrate
      content (LCHO) or caloric equivalency (HCHO). After 2.5 +/- 0.1 h of intense
      cycling to deplete the muscle glycogen stores, subjects (n = 7) received, using a
      rank-ordered design, a CHO-Pro (80 g CHO, 28 g Pro, 6 g fat), LCHO (80 g CHO, 6 g
      fat), or HCHO (108 g CHO, 6 g fat) supplement immediately after exercise (10 min)
      and 2 h postexercise. Before exercise and during 4 h of recovery, muscle glycogen
      of the vastus lateralis was determined periodically by nuclear magnetic resonance
      spectroscopy. Exercise significantly reduced the muscle glycogen stores (final
      concentrations: 40.9 +/- 5.9 mmol/l CHO-Pro, 41.9 +/- 5.7 mmol/l HCHO, 40.7 +/-
      5.0 mmol/l LCHO). After 240 min of recovery, muscle glycogen was significantly
      greater for the CHO-Pro treatment (88.8 +/- 4.4 mmol/l) when compared with the
      LCHO (70.0 +/- 4.0 mmol/l; P = 0.004) and HCHO (75.5 +/- 2.8 mmol/l; P = 0.013)
      treatments. Glycogen storage did not differ significantly between the LCHO and
      HCHO treatments. There were no significant differences in the plasma insulin
      responses among treatments, although plasma glucose was significantly lower
      during the CHO-Pro treatment. These results suggest that a CHO-Pro supplement is
      more effective for the rapid replenishment of muscle glycogen after exercise than
      a CHO supplement of equal CHO or caloric content.

PMID- 12235034
TI  - Effects of intervals between jumps or bouts on osteogenic response to loading.
AB  - Prolonged loading repetitions can diminish the mechanosensitivity of bones, and
      increased intervals between loading might restore sensitivity. This study was
      designed to investigate the effects of intervals between loadings or bouts on
      osteogenic response. Forty female Fisher 344 rats aged 5 wk were divided into a
      control group and three exercise groups: 20 jumps in a single bout with a 3-s
      (S3) or 30-s (S30) jump interval, or 20 jumps in 2 bouts (10 x 2) separated by a
      6-h interval with a 3-s jump interval (D3). After 8 wk of training, the bone
      masses per body weight of the femur and tibia were significantly greater in the
      three exercise groups than in the control group, and these values were also
      greater in S30 than in S3, although they were at the same level in D3 and S3.
      These data suggest that a longer interval (30 s) between individual loading had
      more effective anabolic effects on bone than a shorter interval (3 s).

PMID- 12235035
TI  - Ascent rate, age, maximal oxygen uptake, adiposity, and circulating venous
      bubbles after diving.
AB  - Decompression sickness in diving is recognized as a multifactorial phenomenon,
      depending on several factors, such as decompression rate and individual
      susceptibility. The Doppler ultrasonic detection of circulating venous bubbles
      after diving is considered a useful index for the safety of decompression because
      of the relationship between bubbles and decompression sickness risk. The aim of
      this study was to assess the effects of ascent rate, age, maximal oxygen uptake
      (VO(2 max)), and percent body fat on the production of bubbles after diving.
      Fifty male recreational divers performed two dives at 35 m during 25 min and then
      ascended in one case at 9 m/min and in the other case at 17 m/min. They performed
      the same decompression stops in the two cases. Twenty-eight divers were Doppler
      monitored at 10-min intervals, until 60 min after surfacing, and the data were
      analyzed by Wilcoxon signed-rank test to compare the effect of ascent rate on the
      kinetics of bubbles. Twenty-two divers were monitored 60 min after surfacing. The
      effect on bubble production 60 min after surfacing of the four variables was
      studied in 47 divers. The data were analyzed by multinomial log-linear model. The
      analysis showed that the 17 m/min ascent produced more elevated grades of bubbles
      than the 9 m/min ascent (P < 0.05), except at the 40-min interval, and showed
      relationships between grades of bubbles and ascent rate and age and interaction
      terms between VO(2 max) and age, as well as VO(2 max) and percent body fat.
      Younger, slimmer, or aerobically fitter divers produced fewer bubbles compared
      with older, fatter, or poorly physically fit divers. These findings and the
      conclusions of previous studies performed on animals and humans led us to support
      that ascent rate, age, aerobic fitness, and adiposity are factors of
      susceptibility for bubble formation after diving.

PMID- 12235036
TI  - Role of components of the phagocytic NADPH oxidase in oxygen sensing.
AB  - It has been hypothesized that O(2) sensing in type I cells of the carotid body
      and erythropoietin (EPO)-producing cells of the kidney involves protein
      components identical to the NADPH oxidase system responsible for the respiratory
      burst of phagocytes. In the present study, we evaluated O(2) sensing in mice with
      null mutant genotypes for two components of the phagocytic oxidase. Whole body
      plethysmography was used to study unanesthetized, unrestrained mice. When exposed
      to an acute hypoxic stimulus, gp91(phox)-null mutant and wild-type mice increased
      their minute ventilation by similar amounts. In contrast, p47(phox)-null mutant
      mice demonstrated increases in minute ventilation in response to hypoxia that
      exceeded that of their wild-type counterparts: 98.0 +/- 18.0 vs. 20.0 +/- 13.0%
      (n = 11, P = 0.003). In vitro recordings of carotid sinus nerve (CSN) activity
      demonstrated that resting (basal) neural activity was marginally elevated in
      p47(phox)-null mutant mice. With hypoxic challenge, mean CSN discharge was 1.5
      fold greater in p47(phox)-null mutant than in wild-type mice: 109.61 +/- 13.29
      vs. 72.54 +/- 7.65 impulses/s (n = 8 and 7, respectively, P = 0.026).
      Consequently, the hypoxia-evoked CSN discharge (stimulus-basal) was approximately
      58% larger in p47(phox)-null mutant mice. Quantities of EPO mRNA in kidney were
      similar in gp91(phox)- and p47(phox)-null mutant mice and their respective wild
      type controls exposed to hypobaric hypoxia for 72 h. These findings confirm the
      previous observation that absence of the gp91(phox) component of the phagocytic
      NADPH oxidase does not alter the O(2)-sensing mechanism of the carotid body.
      However, absence of the p47(phox) component significantly potentiates ventilatory
      and chemoreceptor responses to hypoxia. O(2) sensing in EPO-producing cells of
      the kidney appears to be independent of the gp91(phox) and p47(phox) components
      of the phagocytic NADPH oxidase.

PMID- 12235037
TI  - Modulation of upper airway collapsibility during sleep: influence of respiratory
      phase and flow regimen.
AB  - We hypothesized that upper airway collapsibility is modulated dynamically
      throughout the respiratory cycle in sleeping humans by alterations in respiratory
      phase and/or airflow regimen. To test this hypothesis, critical pressures were
      derived from upper airway pressure-flow relationships in six tracheostomized
      patients with obstructive sleep apnea. Pressure-flow relationships were generated
      by varying the pressure at the trachea and nose during tracheostomy (inspiration
      and expiration) (comparison A) and nasal (inspiration only) breathing (comparison
      B), respectively. When a constant airflow regimen was maintained throughout the
      respiratory cycle (tracheostomy breathing), a small yet significant decrease in
      critical pressure was found at the inspiratory vs. end- and peak-expiratory time
      point [7.1 +/- 1.6 (SE) to 6.6 +/- 1.9 to 6.1 +/- 1.9 cmH(2)O, respectively; P <
      0.05], indicating that phasic factors exerted only a modest influence on upper
      airway collapsibility. In contrast, we found that the inspiratory critical
      pressure fell markedly during nasal vs. tracheostomy breathing [1.1 +/- 1.5 (SE)
      vs. 6.1 +/- 1.9 cmH(2)O; P < 0.01], indicating that upper airway collapsibility
      is markedly influenced by differences in airflow regimen. Tracheostomy breathing
      was also associated with a reduction in both phasic and tonic genioglossal muscle
      activity during sleep. Our findings indicate that both phasic factors and airflow
      regimen modulate upper airway collapsibility dynamically and suggest that
      neuromuscular responses to alterations in airflow regimen can markedly lower
      upper airway collapsibility during inspiration.

PMID- 12235038
TI  - Phospholipids modulate the biophysical properties and vasoactivity of PACAP-(1-
      38).
AB  - The purpose of this study was to elucidate the interactions between pituitary
      adenylate cyclase-activating peptide (PACAP)-(1--38) and phospholipids in vitro
      and to determine whether these phenomena modulate, in part, the vasorelaxant
      effects of the peptide in the intact peripheral microcirculation. We found that
      the critical micellar concentration of PACAP-(1--38) was 0.4-0.9 microM. PACAP-(1
      -38) significantly increased the surface tension of a
      dipalmitoylphosphatidylcholine monolayer and underwent conformational transition
      from predominantly random coil in saline to alpha-helix in the presence of
      distearoyl-phosphatidylethanolamine-polyethylene glycol (molecular mass of 2,000
      Da) sterically stabilized phospholipid micelles (SSM) (P < 0.05). Using
      intravital microscopy, we found that aqueous PACAP-(1--38) evoked significant
      concentration-dependent vasodilation in the intact hamster cheek pouch that was
      significantly potentiated when PACAP-(1--38) was associated with SSM (P < 0.05).
      The vasorelaxant effects of aqueous PACAP-(1--38) were mediated predominantly by
      PACAP type 1 (PAC(1)) receptors, whereas those of PACAP-(1--38) in SSM
      predominantly by PACAP/vasoactive intestinal peptide type 1 and 2
      (VPAC(1)/VPAC(2)) receptors. Collectively, these data indicate that PACAP-(1--38)
      self-associates and interacts avidly with phospholipids in vitro and that these
      phenomena amplify peptide vasoactivity in the intact peripheral microcirculation.

PMID- 12235039
TI  - Deep breaths, methacholine, and airway narrowing in healthy and mild asthmatic
      subjects.
AB  - Deep breaths taken before inhalation of methacholine attenuate the decrease in
      forced expiratory volume in 1 s and forced vital capacity in healthy but not in
      asthmatic subjects. We investigated whether this difference also exists by using
      measurements not preceded by full inflation, i.e., airway conductance, functional
      residual capacity, as well as flow and residual volume from partial forced
      expiration. We found that five deep breaths preceding a single dose of
      methacholine 1) transiently attenuated the decrements in forced expiratory volume
      in 1 s and forced vital capacity in healthy (n = 8) but not in mild asthmatic (n
      = 10) subjects and 2) increased the areas under the curve of changes in
      parameters not preceded by a full inflation over 40 min, during which further
      deep breaths were prohibited, without significant difference between healthy (n =
      6) and mild asthmatic (n = 16) subjects. In conclusion, a series of deep breaths
      preceding methacholine inhalation significantly enhances bronchoconstrictor
      response similarly in mild asthmatic and healthy subjects but facilitates
      bronchodilatation on further full inflation in the latter.

PMID- 12235040
TI  - Nitric oxide contributes to 20-HETE-induced relaxation of pulmonary arteries.
AB  - In contrast to its constrictor effects on peripheral arteries, 20
      hydroxyeicosatetraenoic acid (20-HETE) is an endothelial-dependent dilator of
      pulmonary arteries (PAs). The present study examined the hypothesis that the
      vasodilator effects of 20-HETE in PAs are due to an elevation of intracellular
      calcium concentration ([Ca(2+)](i)) and the release of nitric oxide (NO) from
      bovine PA endothelial cells (BPAECs). BPAECs express cytochrome P-450 4A (CYP4A)
      protein and produce 20-HETE. 20-HETE dilated PAs preconstricted with U-46619 or
      norepinephrine and treated with the cytochrome P-450 inhibitor 17-octadecynoic
      acid and the cyclooxygenase inhibitor indomethacin. The dilator effect of 20-HETE
      was blocked by the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester
      (L-NAME) or by removal of endothelium. 20-HETE significantly increased
      [Ca(2+)](i) and NO production in BPAECs. 20-HETE-induced NO release was blunted
      by removal of extracellular calcium, as well as NO synthase inhibitors (L-NAME).
      These results suggest that 20-HETE dilates PAs at least in part by increasing
      [Ca(2+)](i) and NO release in BPAECs.

PMID- 12235041
TI  - Nonuniform activation of the agonist muscle does not covary with index finger
      acceleration in old adults.
AB  - This study examined the patterns of activation in the superficial and deep parts
      of the first dorsal interosseus muscle and in the antagonist muscle, second
      palmar interosseus, during postural tasks (position holding) and slow movements
      (position tracking) of the index finger performed by young and old adults. The
      position-tracking task involved the index finger lifting light loads (2.5, 10,
      and 35% of maximum) with shortening and lengthening contractions as steadily as
      possible. Steadiness was quantified in both tasks as the standard deviation of
      index finger acceleration. The fluctuations in acceleration during the two tasks
      were greater for the old subjects (62-72 yr) compared with young subjects (19-27
      yr), especially with the lightest loads. The two groups of subjects activated the
      superficial and deep parts of first dorsal interosseus at similar intensities
      during the position-holding task, whereas the deep part was more active during
      the shortening and lengthening contractions of the position-tracking task. The
      nonuniform activation of first dorsal interosseus, therefore, was not associated
      with the difference in the standard deviation of acceleration between the young
      and old subjects. Furthermore, there was no association between the average level
      of coactivation by the antagonist muscle and the standard deviation of
      acceleration for either group of subjects across these tasks. Thus the greater
      variability in motor output exhibited by the older adults could not be explained
      by either the nonuniform activation of the agonist muscle or the average level of
      coactivation by the antagonist muscle.

PMID- 12235042
TI  - Interaction between reactive oxygen species and nitric oxide in the microvascular
      response to systemic hypoxia.
AB  - Systemic hypoxia results in oxidative stress due to a change in the reactive
      oxygen species (ROS)-nitric oxide (NO) balance. These experiments explored two
      mechanisms for the altered ROS-NO balance: 1) decreased NO synthesis by NO
      synthase due to limited O(2) substrate availability and 2) increased superoxide
      generation. ROS levels and leukocyte adherence in mesenteric venules of rats
      during hypoxia were studied in the absence and presence of an NO donor [spermine
      NONOate (SNO)] and of the NO precursor L-arginine. We hypothesized that if the
      lower NO levels during hypoxia were due to O(2) substrate limitation, L-arginine
      would not prevent hypoxia-induced microvascular responses. Graded hypoxia
      (produced by breathing 15, 10, and 7.5% O(2)) increased both ROS (123 +/- 6, 148
      +/- 11, and 167 +/- 3% of control) and leukocyte adherence. ROS levels during
      breathing of 10 and 7.5% O(2) were significantly attenuated by SNO (105 +/- 6 and
      108 +/- 3%, respectively) and L-arginine (117 +/- 5 and 115 +/- 2%,
      respectively). Both interventions reduced leukocyte adherence by similar degrees.
      The fact that the effects of L-arginine were similar to those of SNO does not
      support the idea that NO generation is impaired in hypoxia and suggests that
      tissue NO levels are depleted by the increased ROS during hypoxia.

PMID- 12235043
TI  - PGE(2) sensitizes cultured pulmonary vagal sensory neurons to chemical and
      electrical stimuli.
AB  - Mediators of inflammation, such as PGE(2), are known to sensitize the airways to
      inhaled irritants and circulating autacoids. Evidence from in vivo studies has
      shown the involvement of vagal pulmonary C-fiber afferents in the PGE(2)-elicited
      airway hypersensitivity. However, whether PGE(2) acts directly on these sensory
      nerves is unclear. The present study aimed to investigate whether PGE(2) has
      direct potentiating effects on nodose and jugular pulmonary C neurons cultured
      from adult Sprague-Dawley rats and, if so, determine whether the EP(2) prostanoid
      receptor is involved. Pulmonary neurons were identified by retrograde labeling
      with a fluorescent tracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine
      perchlorate. Using perforated patch-clamp technique, our results showed that 1)
      PGE(2) pretreatment (1 microM) increased the whole cell current density elicited
      by capsaicin and phenylbiguanide, chemical agents known to stimulate pulmonary C
      fibers; 2) selective activation of the EP(2) prostanoid receptor by butaprost (3
      10 microM) increased the whole cell current density elicited by capsaicin; and 3)
      PGE(2), as well as butaprost, increased the number of action potentials evoked by
      current injection. Therefore, we conclude that PGE(2) directly sensitizes vagal
      pulmonary C neurons to chemical and electrical stimulation. Furthermore,
      butaprost modulates the neurons in a manner similar to that of PGE(2), suggesting
      that the effects of PGE(2) are mediated, at least in part, through the EP(2)
      prostanoid receptor.

PMID- 12235044
TI  - A finite element model of cell deformation during magnetic bead twisting.
AB  - Magnetic twisting cytometry probes mechanical properties of an adherent cell by
      applying a torque to a magnetic bead that is tightly bound to the cell surface.
      Here we have used a three-dimensional finite element model of cell deformation to
      compute the relationships between the applied torque and resulting bead rotation
      and lateral bead translation. From the analysis, we computed two coefficients
      that allow the cell elastic modulus to be estimated from measurements of either
      bead rotation or lateral bead translation, respectively, if the degree of bead
      embedding and the cell height are known. Although computed strains in proximity
      of the bead can be large, the relationships between applied torque and bead
      rotation or translation remain virtually linear up to bead rotations of 15
      degrees, above which geometrical nonlinearities become significant. This
      appreciable linear range stands in contrast to the intrinsically nonlinear force
      displacement relationship that is observed when cells are indented during atomic
      force microscopy. Finally, these computations support the idea that adhesive
      forces are sufficient to keep the bead firmly attached to the cell surface
      throughout the range of working torques.

PMID- 12235045
TI  - Effects of botulinum toxin A injection and exercise on the growth of juvenile rat
      gastrocnemius muscle.
AB  - Botulinum toxin A (Btx) injections and supervised exercise are often used
      concurrently to treat calf muscle spasticity in children. This study has analyzed
      the early effects of Btx-induced paralysis and increased activity by voluntary
      wheel running on cell growth-related processes in juvenile rat gastrocnemius
      muscle. Btx injection at 29 days of age prevented the normal increases in wet
      mass (50%) and fiber cross-sectional area (34%) seen by 36 days of age in control
      rats. Btx-injected vs. contralateral muscles had 22% fewer myonuclei per fiber
      length but greater than twofold the number of MyoD-positive nuclei at 36 days of
      age. The accretion of 5-bromo-2'-deoxyuridine-labeled newly produced myonuclei
      did not differ between limbs. Voluntary exercise during the 7 days increased the
      mass (18%) and fiber size (23%) of Btx-injected and contralateral muscles but did
      not affect any other variable. Thus Btx injection and exercise had early effects
      on muscle and fiber size without consistently associated changes in myonuclear
      production or number. This suggests the presence of noncontractile activity
      dependent, growth-promoting cytoplasmic events in juvenile muscle.

PMID- 12235046
TI  - A5 cells are silenced when REM sleep-like signs are elicited by pontine
      carbachol.
AB  - The A5 noradrenergic neurons are considered important for cardiorespiratory
      regulation. We hypothesized that A5 cells are silenced during rapid eye movement
      (REM) sleep, thereby contributing to cardiorespiratory changes and suppression of
      hypoglossal (XII) motoneuronal activity. We used an anesthetized, paralyzed, and
      artificially ventilated rat in which pontine microinjections of carbachol trigger
      signs of REM sleep, including hippocampal theta rhythm, motor suppression, and
      silencing of locus coeruleus neurons. All 16 putative noradrenergic A5 cells
      recorded were strongly suppressed when the REM sleep-like episodes were elicited
      and also after intravenous clonidine. Antidromic mapping showed that none of six
      neurons tested projected to the XII nucleus, whereas three of five projected to
      the nucleus of the solitary tract and two of four to the rostral ventrolateral
      medulla. Bilateral microinjections of clonidine into the A5 regions did not alter
      XII nerve activity. These data suggest that A5 neurons are silenced during
      natural REM sleep. This will lead to decreased norepinephrine release and may
      alter synaptic transmission in the nucleus of the solitary tract and rostral
      ventrolateral medulla without, however, a detectable impact on XII motoneurons.

PMID- 12235047
TI  - Exercise effects on muscle beta-adrenergic signaling for MAPK-dependent NKCC
      activity are rapid and persistent.
AB  - This study investigated exercise adaptation of signaling mechanisms that control
      Na(+)-K(+)-2Cl(-) cotransporter (NKCC) activity in rat skeletal muscle. An acute
      bout of exercise increased total and NKCC-mediated (86)Rb influx. Inhibition of
      extracellular signal-regulated kinase (ERK) activation abolished the exercise
      induced NKCC upregulation. Treadmill training (20 m/min, 20% grade, 30 min/day, 5
      days/wk) stimulated total (86)Rb influx and increased NKCC activity in the soleus
      muscle after 2 wk and in the plantaris muscle after 4 wk. Exercise-induced NKCC
      activity was associated with a 1.4- to 2-fold increase in ERK phosphorylation.
      Isoproterenol, which activates ERK and NKCC in sedentary muscle, caused a
      remarkable inhibition of the exercise-induced NKCC activity. Furthermore,
      isoproterenol inhibition of exercise-induced NKCC activity was accompanied with
      decreased ERK phosphorylation in the plantaris muscle. Akt (protein kinase B)
      phosphorylation on both Thr(308) and Ser(473), which activates Akt and inhibits
      NKCC activity in sedentary muscle, was stimulated by acute and chronic exercise.
      This Akt activation was unaffected by isoproterenol. These results indicate an
      immediate and persistent exercise adaptation of the signal pathways that
      participate in the control of potassium transport.

PMID- 12235048
TI  - Does nitric oxide buffer arterial blood pressure variability in humans?
AB  - Animal studies suggest that nitric oxide (NO) plays an important role in
      buffering short-term arterial pressure variability, but data from humans
      addressing this hypothesis are scarce. We evaluated the effects of NO synthase
      (NOS) inhibition on arterial blood pressure (BP) variability in eight healthy
      subjects in the supine position and during 60 degrees head-up tilt (HUT).
      Systemic NOS was blocked by intravenous infusion of N(G)-monomethyl-L-arginine (L
      NMMA). Electrocardiogram and beat-by-beat BP in the finger (Finapres) were
      recorded continuously for 6 min, and brachial cuff BP was recorded before and
      after L-NMMA in each body position. BP and R-R variability and their transfer
      functions were quantified by power spectral analysis in the low-frequency (LF;
      0.05-0.15 Hz) and high-frequency (HF; 0.15-0.35 Hz) ranges. L-NMMA infusion
      increased supine BP (systolic, 109 +/- 4 vs. 122 +/- 3 mmHg, P = 0.03; diastolic,
      68 +/- 2 vs. 78 +/- 3 mmHg, P = 0.002), but it did not affect supine R-R interval
      or BP variability. Before L-NMMA, HUT decreased HF R-R variability (P = 0.03),
      decreased transfer function gain (LF, 12 +/- 2 vs. 5 +/- 1 ms/mmHg, P = 0.007;
      HF, 18 +/- 3 vs. 3 +/- 1 ms/mmHg, P = 0.002), and increased LF BP variability (P
      < 0.0001). After L-NMMA, HUT resulted in similar changes in BP and R-R
      variability compared with tilt without L-NMMA. Increased supine BP after L-NMMA
      with no effect on BP variability during HUT suggests that tonic release of NO is
      important for systemic vascular tone and thus steady-state arterial pressure, but
      NO does not buffer dynamic BP oscillations in humans.

PMID- 12235049
TI  - Effects of exercise and thermal stress on caffeine pharmacokinetics in men and
      eumenorrheic women.
AB  - The influence of gender, exercise, and thermal stress on caffeine
      pharmacokinetics is unclear. We hypothesized that these factors would not have an
      effect on the metabolism of caffeine. Eight women participated in four 8-h trials
      and six men participated in two 8-h trials after the ingestion of 6 mg/kg
      caffeine. The women performed two resting trials (1 in the follicular phase and 1
      in the luteal phase of the menstrual cycle) and two exercise trials (90 min of
      cycling exercise at 65% of maximal O(2) uptake, 1 h after caffeine ingestion) in
      the follicular phase (1 without and 1 with an additional thermal stress). The men
      performed one exercise and one resting trial. Menstrual cycle, gender, and
      exercise, with or without an additional thermal stress, had no effect on the
      pharmacokinetic measurements or urine caffeine. There was a trend for higher
      plasma caffeine and lower plasma paraxanthine concentrations in the women. These
      results confirm that gender, exercise, and thermal stress have no effect on
      caffeine pharmacokinetics in men and women.

PMID- 12235050
TI  - Vascular response to infusions of a nonextravasating hemoglobin polymer.
AB  - The clinical utility of cross-linked tetrameric hemoglobin solutions is limited
      by peripheral vasoconstriction thought to be due to scavenging of nitric oxide.
      In addition, transfusion of crude preparations of hemoglobin polymers can cause
      arterial hypertension. We tested the hypothesis that eliminating low-molecular
      weight components from the polymer solution would prevent extravasation and its
      associated pressor response. A zero-link polymer of bovine hemoglobin was
      developed without chemical linkers left between the tetramers. Transfusion of
      unprocessed preparations of these polymers in rats resulted in appearance of the
      polymer in the renal hilar lymph. However, eliminating the low-molecular-weight
      components with a 300-kDa diafiltration resulted in an average hydrodynamic
      radius of 250 A and in undetectable levels of polymer in hilar lymph. Exchange
      transfusion in anesthetized rats and cats and in awake cats produced no increase
      in arterial pressure. In anesthetized cats, exchange transfusion with an albumin
      solution reduced hematocrit from 30 to 18%, increased cerebral blood flow, and
      dilated pial arterioles. In contrast, reducing hematocrit by transfusing the
      diafiltered polymer did not increase cerebral blood flow as pial arterioles
      constricted. These results are consistent with the hypothesis that the increase
      in arterial pressure associated with cell-free hemoglobin transfusion depends on
      hemoglobin extravasation. Constriction observed in the cerebrovascular bed with a
      nonextravasating hemoglobin polymer at low hematocrit is presumably a regulatory
      response to prevent overoxygenation at low blood viscosity.

PMID- 12235051
TI  - Mechanical properties of rat soleus after long-term spinal cord transection.
AB  - The effects of a complete spinal cord transection (ST) on the mechanical
      properties of the rat soleus were assessed 3 and 6 mo post-ST and compared with
      age-matched controls. Maximal tetanic force was reduced by approximately 44 and
      approximately 25% at 3 and 6 mo post-ST, respectively. Similarly, maximum twitch
      force was reduced by approximately 29% in 3-mo and approximately 17% in 6-mo ST
      rats. ST resulted in faster twitch properties as evidenced by shorter time to
      peak tension (approximately 45%) and half-relaxation time (approximately 55%) at
      both time points. Maximum shortening velocity was significantly increased in ST
      rats whether measured by extrapolation from the force-velocity curve
      (approximately twofold at both time points) or by slack-test measurements (over
      twofold at both time points). A significant reduction in fatigue resistance of
      the soleus was observed at 3 (approximately 25%) and 6 mo (approximately 45%)
      post-ST. For the majority of the speed-related properties, no significant
      differences were detected between 3- and 6-mo ST rats. However, the fatigue
      resistance of the soleus was significantly lower in 6- vs. 3-mo ST rats. These
      data suggest that, between 3 and 6 mo post-ST, force-related properties tended to
      recover, speed-related properties plateaued, and fatigue-related properties
      continued to decline. Thus some specific functional properties of the rat soleus
      related to contractile force, speed, and fatigue adapted independently after ST.

PMID- 12235052
TI  - Living high-training low increases hypoxic ventilatory response of well-trained
      endurance athletes.
AB  - This study determined whether "living high-training low" (LHTL)-simulated
      altitude exposure increased the hypoxic ventilatory response (HVR) in well
      trained endurance athletes. Thirty-three cyclists/triathletes were divided into
      three groups: 20 consecutive nights of hypoxic exposure (LHTLc, n = 12), 20
      nights of intermittent hypoxic exposure (four 5-night blocks of hypoxia, each
      interspersed with 2 nights of normoxia, LHTLi, n = 10), or control (Con, n = 11).
      LHTLc and LHTLi slept 8-10 h/day overnight in normobaric hypoxia (approximately
      2,650 m); Con slept under ambient conditions (600 m). Resting, isocapnic HVR
      (DeltaVE/DeltaSp(O(2)), where VE is minute ventilation and Sp(O(2)) is blood O(2)
      saturation) was measured in normoxia before hypoxia (Pre), after 1, 3, 10, and 15
      nights of exposure (N1, N3, N10, and N15, respectively), and 2 nights after the
      exposure night 20 (Post). Before each HVR test, end-tidal PCO(2) (PET(CO(2))) and
      VE were measured during room air breathing at rest. HVR (l. min(-1). %(-1)) was
      higher (P < 0.05) in LHTLc than in Con at N1 (0.56 +/- 0.32 vs. 0.28 +/- 0.16),
      N3 (0.69 +/- 0.30 vs. 0.36 +/- 0.24), N10 (0.79 +/- 0.36 vs. 0.34 +/- 0.14), N15
      (1.00 +/- 0.38 vs. 0.36 +/- 0.23), and Post (0.79 +/- 0.37 vs. 0.36 +/- 0.26).
      HVR at N15 was higher (P < 0.05) in LHTLi (0.67 +/- 0.33) than in Con and in
      LHTLc than in LHTLi. PET(CO(2)) was depressed in LHTLc and LHTLi compared with
      Con at all points after hypoxia (P < 0.05). No significant differences were
      observed for VE at any point. We conclude that LHTL increases HVR in endurance
      athletes in a time-dependent manner and decreases PET(CO(2)) in normoxia, without
      change in VE. Thus endurance athletes sleeping in mild hypoxia may experience
      changes to the respiratory control system.

PMID- 12235053
TI  - Three-dimensional mapping of smooth muscle in the distal conducting airways of
      mouse, rabbit, and monkey.
AB  - Airway smooth muscle remodeling is implicated in a number of constrictive
      pulmonary diseases such as asthma and may include changes in smooth muscle
      orientation and abundance. Both factors were compared in the normal distal
      bronchioles of the mouse, rabbit, and rhesus monkey (respiratory bronchioles
      included). Airway smooth muscle was measured by using a three-dimensional
      approach employing confocal microscopy and whole-mount cytochemistry with
      fluorochrome-conjugated phalloidin, a probe for polymerized actin. Smooth muscle
      orientation had a wide range of angles along the airway, but the distribution was
      conserved among species and among distal airway generations. At the bifurcation
      of proximal bronchioles, smooth muscle was nearly parallel to the longitudinal
      axis of the airway. Smooth muscle abundance was significantly different between
      species (abundance was less in the monkey compared with the mouse and rabbit),
      and there was a trend for abundance to decrease with each more distal airway
      generation. This study defines the normal distribution of smooth muscle in three
      test species and provides a basis for future comparisons with the diseased state.

PMID- 12235054
TI  - Phonospirometry for noninvasive measurement of ventilation: methodology and
      preliminary results.
AB  - We measured tracheal flow from tracheal sounds to estimate tidal volume, minute
      ventilation (VI), respiratory frequency, mean inspiratory flow (VT/TI), and duty
      cycle (TI/Ttot). In 11 normal subjects, 3 patients with unstable airway
      obstruction, and 3 stable asthmatic patients, we measured tracheal sounds and
      flow twice: first to derive flow-sound relationships and second to obtain flow
      volume relationships from the sound signal. The flow-volume relationship was
      compared with pneumotach-derived volume. When subjects were seated, facing
      forward and with neck rotation, flexion, and standing, flow-volume relationship
      was within 15% of pneumotach-derived volume. Error increased with neck extension
      and while supine. We then measured ventilation without mouthpiece or nose clip
      from tracheal sounds during quiet breathing for up to 30 min. Normal results +/-
      SD revealed tidal volume = 0.37 +/- 0.065 liter, respiratory frequency = 19.3 +/-
      3.5 breaths/min, VI = 6.9 +/- 1.2 l/min, VT/TI = 0.31 +/- 0.06 l/s, and TI/Ttot =
      0.37 +/- 0.04. Unstable airway obstruction had large VI due to increased VT/TI.
      With the exception of TI/Ttot, variations in ventilatory parameters were closer
      to log normal than normal distributions and tended to be greater in patients. We
      conclude that phonospirometry measures ventilation reasonably accurately without
      mouthpiece, nose clip, or rigid postural constraints.

PMID- 12235055
TI  - Historical perspectives on lung edema clearance.
AB  - Early studies of fluid transport across the pulmonary epithelium were conducted
      in intact animals or isolated lungs. Although the location and cells responsible
      for transport cannot be determined with studies in whole mammalian lungs, such
      preparations remain indispensable for determining the physiological and clinical
      relevance of in vitro investigations of cells and their transport proteins. Three
      different approaches have been used to study transport and exchange between the
      vascular and air space compartments in intact lungs. Some of the advantages and
      limitations of these methods are briefly reviewed here.

PMID- 12235056
TI  - Invited review: Active fluid clearance from the distal air spaces of the lung.
AB  - Active ion transport drives iso-osmolar alveolar fluid clearance, a hypothesis
      originally suggested by in vivo studies in sheep 20 yr ago. Over the last two
      decades, remarkable progress has been made in establishing a critical role for
      active sodium transport as a primary mechanism that drives fluid clearance from
      the distal air spaces of the lung. The rate of fluid transport can be increased
      in most species, including the human lung, by cAMP stimulation. Catecholamine
      independent mechanisms, including hormones, growth factors, and cytokines, can
      also upregulate epithelial fluid clearance in the lung. The new insights into the
      role of the distal lung epithelium in actively regulating lung fluid balance has
      important implications for the resolution of clinical pulmonary edema.

PMID- 12235057
TI  - Invited review: Clearance of lung liquid during the perinatal period.
AB  - At birth, the distal lung epithelium undergoes a profound phenotypic switch from
      secretion to absorption in the course of adaptation to air breathing. In this
      review, we describe the developmental regulation of key membrane transport
      proteins and the way in which epinephrine, oxygen, glucocorticoids, and thyroid
      hormones interact to bring about this crucial change in function. Evidence from
      molecular, transgenic, cell culture, and whole lung studies is presented, and the
      clinical consequences of the failure of the physiological mechanisms that
      underlie perinatal lung liquid absorption are discussed.

PMID- 12235059
TI  - Selected contribution: Lung hypoxia: antioxidant and antiapoptotic effects of
      liposomal alpha-tocopherol.
AB  - The aim of this study is to examine the antioxidant and antiapoptotic activity of
      liposomal alpha-tocopherol (LAT) in anesthetized rats exposed to severe hypoxia.
      It was shown that intratracheal application of LAT normalized lung phospholipid
      composition and inhibited lipid peroxidation in lung tissues, which in turn
      decreased lung edema and damage and improved breathing pattern, oxygen diffusion,
      and lung gas exchange. LAT also limited the overexpression of genes encoding
      hypoxia inducible factor-1alpha and both studied forms of phospholipase A(2), and
      it increased the power of cellular antioxidant and antiapoptotic defense by
      overexpressing genes encoding Mn- and Cu-Zn-cofactored superoxide dismutases, Bcl
      2, and heat shock 70 proteins. The overexpression of studied caspases and their
      activity were downregulated, which significantly (1.6-2 times) limited apoptosis
      in lung cells. Finally, all these positive changes decreased mortality during
      hypoxia from approximately 60% in untreated animals to approximately 30% in the
      group of rats treated with LAT. The data obtained indicate that LAT may be useful
      for the correction of hypoxic lung injury.

PMID- 12235061
TI  - FAP: another indication to treat H pylori.

PMID- 12235060
TI  - Hepatocellular carcinoma: is current therapy really altering outcome?
AB  - Progress in the management of hepatocellular carcinoma (HCC) has been slow and
      has limited impact on outcome. Most patients with HCC have two diseases--chronic
      liver disease and HCC--and complex interactions between the two have major
      implications for diagnosis and prognosis as well as the management of HCC. The
      disease is most prevalent in those areas of the world where the infrastructure
      for clinical trials is least developed. Also, the aetiology of the disease varies
      around the world and it is still not known whether HCCs of different aetiologies
      have different prognoses. Current treatment is making an impact on the management
      of HCC but further progress awaits not only the development of more effective
      treatments but also the development of adequate methodologies to assess the
      impact of these treatments.

PMID- 12235062
TI  - Functional dyspepsia: bye-bye to PPIs.

PMID- 12235063
TI  - Do those with positive faecal occult blood tests need upper gastrointestinal
      investigations if no colorectal cancer cause is found?

PMID- 12235065
TI  - Laparoscopic fundoplication is the treatment of choice for gastro-oesophageal
      reflux disease. Antagonist.

PMID- 12235064
TI  - Laparoscopic fundoplication is the treatment of choice for gastro-oesophageal
      reflux disease. Protagonist.

PMID- 12235066
TI  - Mechanisms of gastro-oesophageal reflux in preterm and term infants with reflux
      disease.
AB  - BACKGROUND: Transient lower oesophageal sphincter relaxation (TLOSR) is the
      predominant mechanism of gastro-oesophageal reflux (GOR) in healthy infants but
      the mechanisms of GOR in infants with GOR disease (GORD) are poorly understood.
      AIMS: To measure the occurrence of TLOSR, GOR, and gastric emptying (GE) rate in
      preterm and term infants with GORD. PATIENTS: Thirty six infants were studied and
      grouped as normals or GORD based on a routine clinical assessment and
      confirmation of an assessment of GORD by reflux symptom charts and oesophageal pH
      monitoring. METHODS: A micromanometric assembly incorporating a micro pH
      electrode recorded oesophageal motility and pH. GE rate was determined using the
      (13)C-octanoic acid breath test. RESULTS: TLOSR was the predominant mechanism of
      GOR, triggering 50-100% of GOR episodes (median 91.5%). Abdominothoracic
      straining significantly increased the occurrence of GOR in association with
      TLOSR. In infants with GORD, the number of TLOSRs overall was similar to normals
      but the proportion of TLOSRs accompanied by acid GOR was significantly higher
      than in normals (16.5% v 5.7%, respectively; p<0.001). Infants with GORD had a
      similar GE rate to normals. CONCLUSIONS: In infant GORD, acid reflux associated
      TLOSRs are abnormally common and likely to be a major contributing factor to the
      pathophysiology of GORD. Infants with GORD do not have delayed GE.

PMID- 12235067
TI  - Relationship between Helicobacter pylori babA2 status with gastric epithelial
      cell turnover and premalignant gastric lesions.
AB  - BACKGROUND: Helicobacter pylori blood group antigen binding adhesin (BabA)
      mediates bacterial adherence to human blood group antigens on gastric epithelium.
      Although strains harbouring babA2 were recently found to be associated with
      peptic ulcer and gastric cancer, the role of babA2 in cellular turnover, severity
      of gastritis, and premalignant changes is poorly understood. AIM: We correlated H
      pylori babA2, vacuolating toxin (vacA), and cytotoxin associated gene A (cagA)
      genotypes with the severity of gastric inflammation and epithelial cell turnover
      in a group of Chinese patients from an area with a high incidence of gastric
      cancer. PATIENTS AND METHODS: H pylori isolates were obtained from 104 Chinese
      patients who participated in a gastric cancer prevention programme. Genotype
      variants of babA2, vacA, and cagA were determined by polymerase chain reaction.
      Antrum and corpus histopathology was examined according to the updated Sydney
      classification. Apoptosis was scored by terminal uridine deoxynucleotidyl nick
      end labeling (TUNEL) and proliferation by Ki-67 immunostaining. RESULTS: Of the
      104 patients, 102 (98.1%) harboured cagA(+) strains and all had vacA s1 genotype.
      The babA2(+) strains were found in 83 (79.8%) patients and were associated with
      higher lymphocytic infiltration (p=0.028), presence of glandular atrophy (odds
      ratio (OR) 7.5, 95% confidence interval (CI) 2.3-24.3), and intestinal metaplasia
      (OR 7.4, 95% CI 2.2-25.3) in the antrum. Increased epithelial proliferation was
      also noted in individuals infected with babA2(+) strains (p=0.025). Strains
      harbouring cagA(+)/vacA s1 genotypes lacked this association in the absence of
      babA2. CONCLUSIONS: The presence of babA2(+) H pylori strains alone or in
      combination with cagA(+) and vacA s1 was associated with the presence of
      preneoplastic gastric lesions.

PMID- 12235068
TI  - Impact of Helicobacter pylori infection and mucosal atrophy on gastric lesions in
      patients with familial adenomatous polyposis.
AB  - BACKGROUND AND AIMS: The role of Helicobacter pylori and atrophic gastritis in
      the pathogenesis of gastric lesions in familial adenomatous polyposis (FAP) has
      not been clarified. PATIENTS: Thirty one patients with FAP. METHODS: The presence
      of fundic gland polyposis (FGP) and gastric adenoma (GA) was determined by upper
      endoscopy with biopsies. The degree of gastric mucosal atrophy and H pylori
      status were determined by serological and histological findings. Germline
      mutation in the adenomatous polyposis coli (APC) gene was determined by
      polymerase chain reaction based single strand conformation polymorphism and
      direct sequencing. RESULTS: Gastric lesions were detected in 23 patients (74%).
      FGP and GA were found in 52% and 39%, respectively. APC gene mutation was
      identified in 22 of 30 patients. Patients with FGP were less frequently infected
      with H pylori than those without FGP (13% v 67%). The former patients had a lower
      degree of atrophy than the latter. Patients with GA tended to be more frequently
      infected with H pylori and they had higher degrees of atrophy than those without
      GA. When subjects were subdivided by gastric lesions (FGP alone, FGP+GA, GA
      alone, and negative groups), the GA alone group had the lowest pepsinogen I/II
      ratio and the highest seropositivity for H pylori. GA was found more frequently
      in patients positive for the APC mutation whereas no such a trend was observed in
      FGP. CONCLUSIONS: In FAP, H pylori associated atrophic gastritis contributes
      negatively to FGP. It seems to contribute positively to GA, especially in
      patients with truncating APC gene mutation.

PMID- 12235069
TI  - Impact of acid secretion, gastritis, and mucus thickness on gastric transfer of
      antibiotics in rats.
AB  - BACKGROUND AND AIMS: The success of Helicobacter pylori eradication regimens
      depends on gastric pH, inflammation, and mucus thickness. Our aim was to
      investigate the effects of acid secretion, inflammation, and mucolysis on gastric
      antibiotic transfer. SUBJECTS AND METHODS: A total of 134 anaesthetised rats were
      given metronidazole, amoxicillin, or clarithromycin intravenously and gastric
      contents were aspirated via an indwelling cannula. Acid secretion was controlled
      by either omeprazole or pentagastrin while gastritis was induced by infection
      with H pylori or dosing with iodoacetamide. Mucolysis was achieved by instilling
      pronase into the gastric lumen. RESULTS: Metronidazole transfer increased with
      acid secretion and fell with omeprazole, independently of gastric pH.
      Clarithromycin was also transferred with acid but was then rapidly degraded.
      Omeprazole prevented this degradation, raising gastric luminal concentrations.
      Omeprazole did not alter amoxicillin transfer. Gastritis induced by H pylori did
      not alter gastric transfer of metronidazole and amoxicillin but that of
      clarithromycin was increased by 23%. However, gastritis induced by iodoacetamide
      reduced clarithromycin transfer without any effect on metronidazole or
      amoxicillin transfer. Pronase treatment increased amoxicillin transfer fourfold
      and metronidazole by 66% but reduced clarithromycin transfer by 35%. CONCLUSIONS:
      Metronidazole and clarithromycin are predominantly transferred with gastric acid
      rather than by an acid trapping mechanism. Pronase increases the appearance of
      amoxicillin and metronidazole in gastric secretions.

PMID- 12235070
TI  - Pan-colonic decrease in interstitial cells of Cajal in patients with slow transit
      constipation.
AB  - BACKGROUND: Interstitial cells of Cajal (ICC) are required for normal intestinal
      motility. ICC are found throughout the human colon and are decreased in the
      sigmoid colon of patients with slow transit constipation. AIMS: The aims of this
      study were to determine the normal distribution of ICC within the human colon and
      to determine if ICC are decreased throughout the colon in slow transit
      constipation. PATIENTS: The caecum, ascending, transverse, and sigmoid colons
      from six patients with slow transit constipation and colonic tissue from patients
      with resected colon cancer were used for this study. METHODS: ICC cells were
      identified with a polyclonal antibody to c-Kit, serial 0.5 microm sections were
      obtained by confocal microscopy, and three dimensional software was employed to
      reconstruct the entire thickness of the colonic muscularis propria and submucosa.
      RESULTS: ICC were located within both the longitudinal and circular muscle
      layers. Two networks of ICC were identified, one in the myenteric plexus region
      and another, less defined network, in the submucosal border. Caecum, ascending
      colon, transverse colon, and sigmoid colon displayed similar ICC volumes. ICC
      volume was significantly lower in the slow transit constipation patients across
      all colonic regions. CONCLUSIONS: The data suggest that ICC distribution is
      relatively uniform throughout the human colon and that decreased ICC volume is
      pan-colonic in idiopathic slow transit constipation.

PMID- 12235071
TI  - Double blind, randomised, placebo controlled study of four weeks of lansoprazole
      for the treatment of functional dyspepsia in Chinese patients.
AB  - BACKGROUND: The use of proton pump inhibitors for the treatment of functional
      dyspepsia is controversial and the role of Helicobacter pylori infection in
      functional dyspepsia is uncertain. AIM: To evaluate the efficacy of different
      doses of lansoprazole for the treatment of functional dyspepsia in Chinese
      patients. METHOD: Patients with a clinical diagnosis of functional dyspepsia
      according to the Rome II criteria and normal upper gastrointestinal endoscopy
      were recruited and randomised to receive: (1) lansoprazole 30 mg, (2)
      lansoprazole 15 mg, or (3) placebo, all given daily for four weeks. Dyspepsia
      symptom scores and quality of life (SF-36 score) were evaluated before and four
      weeks after treatment. RESULTS: A total of 453 patients were randomised. There
      was no difference in the proportion of patients with complete symptom relief in
      the lansoprazole 30 mg (23%) and lansoprazole 15 mg (23%) groups compared with
      the placebo group (30%). The proportion of H pylori positive patients with a
      complete response was similar with lansoprazole 30 mg (34%) and lansoprazole 15
      mg (20%) versus placebo (22%). All symptom subgroups (ulcer-like, dysmotility
      like, reflux-like, and unspecified dyspepsia) had similar proportions of patients
      with complete symptom relief after treatment. CONCLUSION: Proton pump inhibitor
      treatment is not superior to placebo for the management of functional dyspepsia
      in Chinese patients.

PMID- 12235072
TI  - Effect of stress on the paracellular barrier in the rat ileum.
AB  - BACKGROUND: Restraint stress induces permeability changes in the rat small
      intestine but little is known of the ultrastructural events leading to defects of
      the paracellular sealing or of the short term evolution of these alterations.
      METHODS: In the present study, we performed transmission electron microscopy in
      the terminal ileum perfused with lanthanum after two hours of immobilisation
      stress and in non-stressed control rats. Moreover, immunohistochemistry of the
      tight junction (TJ) associated proteins, occludin and zonula occludens 1 (ZO-1),
      was carried out together with western blot analysis of the transmembrane protein
      occludin. TJ morphology was also assessed after a 22 hour recovery period.
      RESULTS: Immobilisation stress induced a significant increase in epithelial
      permeability to the lanthanum tracer (p<0.005) which recovered completely after
      22 hours. Compared with unstressed controls, in stressed rats no differences were
      found on freeze fracture analysis. The TJ related immunofluorescence signals of
      occludin and of ZO-1 were irregularly distributed in stressed rats after two
      hours but returned to a normal pattern at 24 hours although with minor intensity.
      No quantitative alterations in occludin were detectable in stressed rats by
      immunoblot whereas a perinuclear concentration of occludin was observed by
      immunolocalisation. CONCLUSIONS: Immobilisation stress induced an increase in TJ
      permeability in the rat terminal ileum. These changes were mainly due to
      modifications and redistribution of the TJ transmembrane protein occludin and of
      the plaque protein ZO-1 whereas protein synthesis, at least that of occludin, was
      not affected by stress.

PMID- 12235073
TI  - Autophagocytosis of the apical membrane in microvillus inclusion disease.
AB  - BACKGROUND: Microvillus inclusion disease (MID) is a disorder with the clinical
      signs of intractable diarrhoea in the newborn and infancy. The typical
      pathological features of the disease are well known whereas the pathophysiology
      is still unclear. AIM: This study was performed to define possible alterations of
      the cytoskeleton and exocytic as well as endocytic pathways within enterocytes in
      MID. PATIENTS: Four patients with MID were studied. Three had a congenital onset
      of diarrhoea and one patient had a late onset form. METHODS: Thin frozen sections
      of small bowel biopsies of patients were labelled by antibodies against the
      cytoskeleton and the brush border enzyme sucrase-isomaltase. The binding sites of
      the primary antibodies were visualised by immunogold particles in the electron
      microscope. Biopsies were labelled in organ culture to analyse the biosynthetic
      and endocytic pathways within the enterocytes. RESULTS: Labelling with antibodies
      against actin and villin did not differ significantly in control and patient
      biopsies. Biosynthetic labelling revealed normal intracellular processing and
      transport of the brush border enzyme sucrase-isomaltase. Secretory granules in
      crypt epithelial cells were positive for sucrase-isomaltase, differing in its
      labelling density between patients. Patient biopsies showed microvillus inclusion
      bodies which endocytosed cationised ferritin within five minutes after uptake as
      well as ovalbumin after incubation for 10 minutes. These microvillus inclusion
      bodies correspond to early endosomes because they lack lysosome associated
      membrane proteins. Late endosomes and lysosomes containing sucrase-isomaltase did
      not reveal microvillus-like structures. CONCLUSION: Microvillus inclusion bodies
      in MID originate from autophagocytosis of the apical membrane of enterocytes with
      engulfing of microvilli.

PMID- 12235074
TI  - Antidiarrhoeal properties of a novel sigma ligand (JO 2871) on toxigenic
      diarrhoea in mice: mechanisms of action.
AB  - BACKGROUND AND AIMS: Sigma ligands display antisecretory activity against various
      secretagogues, suggesting antidiarrhoeal properties. In this study, we evaluated:
      (i) the antidiarrhoeal effect of JO 2871, a high affinity sigma ligand, in three
      models of toxigenic diarrhoea in mice; and (ii) the site and mechanism of action
      of this compound. METHODS: Faeces were collected after toxin or vehicle
      administration in male DBA2 or NMRI mice. Diarrhoea was determined by cumulative
      stool weight (mg) over a 120 minute period. Diarrhoea was induced by intravenous
      administration of Salmonella enteriditis lipopolysaccharide (LPS), or oral
      administration of Escherichia coli heat stable (E coli-sta) or Clostridium
      difficile toxins. Two sigma ligands, igmesine and JO 2871, were administered
      either orally or intravenously, 60 and 30 minutes before the toxins,
      respectively. JO 2871 was also given orally 30 minutes after E coli-sta. In
      addition, JO 2871 was administered intracerebroventricularly five minutes before
      LPS and E coli-sta. BMY 14802 (1000 microg/kg orally), a sigma receptor
      antagonist, or cyclosomatostatin (CSS 1 microg/kg intravenously), a somatostatin
      antagonist, were given five minutes prior to JO 2871 in LPS, E coli-sta, and C
      difficile toxin treated mice. Gastric emptying and intestinal transit were
      evaluated after oral JO 2871 and BMY 14802 and intravenous CSS. RESULTS: Stool
      weight measured 120 minutes after administration of the toxins was significantly
      increased. Oral JO 2871 and igmesine dose dependently inhibited toxigenic
      diarrhoea in all models. ED(50) values obtained using JO 2871 (1-20 microg/kg)
      were more than 40 times lower than those obtained with igmesine. Oral JO 2871
      given after E coli-sta also inhibited diarrhoea in a dose dependent manner
      (ED(50) 50 microg/kg). Both sigma ligands were active by the intravenous route on
      LPS and E coli-sta induced stool weight increases. JO 2871 administered
      intracerebroventricularly failed to block this effect at any dose tested. Both
      BMY 14802 and CSS reversed the antidiarrhoeal effect of oral JO 2871. JO 2871,
      BMY 14802, and CSS did not affect transit parameters. CONCLUSIONS: JO 2871 exerts
      a potent oral antidiarrhoeal effect, acting peripherally through sigma sites and
      somatostatin release.

PMID- 12235075
TI  - ICAM-1 and VCAM-1 antisense oligonucleotides attenuate in vivo leucocyte
      adherence and inflammation in rat inflammatory bowel disease.
AB  - BACKGROUND: Recruitment of circulating cells to the inflamed intestine is
      modulated by adhesion molecules expressed on the surface of both leucocytes and
      endothelial cells. AIMS: The objective of this study was to test whether 2'-O
      methoxyethyl chimeric antisense oligonucleotides directed against endothelial
      intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1
      (VCAM-1) can downregulate leucocyte-endothelial interactions and thereby
      attenuate inflammation in rat experimental ileitis. METHODS: Indomethacin (7.5
      mg/kg ) was injected subcutaneously into Sprague-Dawley rats 48 and 24 hours
      prior to intravital microscopy. Animals were treated with either ICAM-1 (ISIS
      17470), VCAM-1 (ISIS 18155), or scrambled control antisense oligonucleotides
      administered subcutaneously or intravenously in parallel with indomethacin.
      Leucocyte trafficking was observed in ileal submucosal collecting venules.
      Macroscopic and histological grades of inflammation were measured 48 hours after
      the first indomethacin application. ICAM-1 and VCAM-1 expression in ileal
      submucosal venules was detected by immunohistochemistry. RESULTS: Intravenous
      administration of ICAM-1 oligonucleotides 2 mg/kg (rolling leucocytes 5.7
      (2.4)/0.01 mm(2) endothelial surface, adherent leucocytes 0.8 (1.1)) and VCAM-1
      oligonucleotides 8 mg/kg (9.2 (4.4), 0.6 (0.8)) significantly reduced leucocyte
      adhesion compared with diseased controls (27.8 (5.3), 14 (4.4)) in a dose
      dependent manner whereas subcutaneous treatment did not. Correspondingly,
      macroscopic and histological inflammation was significantly decreased. ICAM-1
      oligonucleotides markedly reduced endothelial ICAM-1 expression while VCAM-1
      oligonucleotides clearly diminished endothelial VCAM-1 expression. CONCLUSIONS:
      Both ICAM-1 and VCAM-1 2'-O-methoxyethyl chimeric antisense oligonucleotides
      attenuate rat ileitis by downregulation of leucocyte adherence and thus are
      potential candidates for anti-inflammatory treatment in inflammatory bowel
      disease.

PMID- 12235076
TI  - Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the
      basis of suspected adverse reaction reports to the Committee on Safety of
      Medicines.
AB  - BACKGROUND: 5-aminosalicylates are extensively prescribed for the treatment of
      ulcerative colitis but have a wide range of described adverse effects. AIMS: To
      determine whether serious adverse effect profiles differ for sulphasalazine and
      mesalazine. METHODS: Analysis of suspected serious adverse reactions reported to
      the Committee on Safety of Medicines of the UK in 1991-1998. Adverse effect
      profiles were categorised for interstitial nephritis, pancreatitis, serious skin
      reactions, hepatitis and hepatic failure, and blood dyscrasias. Report rates were
      calculated using prescribing data from the Department of Health and compared for
      mesalazine and sulphasalazine. Further analysis was undertaken for sulphasalazine
      according to disease indication of inflammatory bowel disease or rheumatoid
      arthritis. RESULTS: A total of 4.7 million prescriptions were dispensed for
      sulphasalazine compared with 2.8 million for mesalazine. Interstitial nephritis
      was only described for mesalazine, with 11.1 reports per million prescriptions.
      Pancreatitis was reported seven times as frequently for mesalazine (7.5 per
      million prescriptions) compared with sulphasalazine (1.1 per million
      prescriptions) (odds ratio (OR) 7.0; 95% confidence interval (CI) 2.6-18.6;
      p<0.001). There were no reports of serious skin disorders in patients prescribed
      sulphasalazine for inflammatory bowel disease. Blood dyscrasias were reported
      significantly more often in patients receiving sulphasalazine for rheumatoid
      arthritis than for inflammatory bowel disease (OR 5.31; 95% CI 2.6-11.0;
      p<0.001), and there was a similar trend for hepatic disorders. CONCLUSIONS:
      Spontaneous reports suggest that within the five sets of disorders considered,
      there is no evidence to indicate a safety advantage of mesalazine over
      sulphasalazine in the treatment of inflammatory bowel disease. Pancreatitis and
      interstitial nephritis appear significantly more common with mesalazine, and
      advice on renal monitoring in patients who receive mesalazine may need
      reinforcing.

PMID- 12235077
TI  - Upregulation of matrix metalloproteinases in a model of T cell mediated tissue
      injury in the gut: analysis by gene array and in situ hybridisation.
AB  - BACKGROUND AND AIM: Matrix metalloproteinases (MMPs) have been implicated in
      tissue remodelling and ulceration in inflammatory bowel disease and coeliac
      disease. Studies to date have concluded that stromelysin 1 is functionally
      involved in mucosal degradation. However, there are many other MMPs whose
      function in the gut is currently unknown. This work had two aims: firstly, to use
      gene array technology to measure changes in MMP and tissue inhibitor of
      metalloproteinase (TIMP) expression in a model of T cell mediated injury in the
      gut, and secondly, to correlate data from gene arrays with that generated by in
      situ hybridisation. METHODS: T cells in explants of human fetal gut were
      activated with pokeweed mitogen or anti-CD3 plus interleukin 12. Gene array
      analysis and in situ hybridisation were performed to investigate changes in MMP
      gene expression. RESULTS: Both gene array analysis and in situ hybridisation
      indicated marked upregulation of stromelysin 2 and macrophage metalloelastase
      expression in the explants associated with mucosal destruction. The arrays also
      confirmed our previous observation that interstitial collagenase (MMP-1),
      stromelysin 1 (MMP-3), and gelatinase B (MMP-9) are upregulated but there was no
      change in MMP-2, -7, -8, -9, -11, -13, -14-17, or -19. Following T cell
      activation, transcripts for TIMPs were reduced. CONCLUSIONS: These results show
      that there is differential upregulation of MMPs during T cell responses in the
      gut and suggest that further studies on the role of stromelysin 2 and macrophage
      metalloelastase may show that they have a functional role. In addition, the
      increase in MMPs and reduction in TIMPs suggest that the protease/antiprotease
      balance in the mucosa may determine the extent of mucosal degradation.

PMID- 12235078
TI  - Which 5-ASA?

PMID- 12235079
TI  - Flat and depressed colorectal tumours in a southern Swedish population: a
      prospective chromoendoscopic and histopathological study.
AB  - BACKGROUND: Flat and depressed colorectal tumours are common in Japan but are
      very rare or non-existent in Western countries. AIMS: To study the occurrence of
      flat colorectal tumours in a southern Swedish population. METHODS: In this
      prospective study, 371 consecutive European patients were examined by high
      resolution video colonoscopy combined with chromoendoscopy. The nature of the
      lesions was determined by histopathological examination. RESULTS: A total of 973
      tumours were found; 907 (93.2%) were protruding and 66 (6.8%) were flat or
      depressed. Of the flat/depressed tumours, five (7.7%) were early adenocarcinomas
      infiltrating the submucosa. Eleven carcinomas (1.2%) were found among protruding
      tumours. High grade dysplasia was observed in 18% (n=11) of flat/depressed
      adenomas in contrast with 7.3% (n=65) of protruding adenomas, and occurred in
      smaller flat/depressed tumours compared with protruding ones (mean diameter 8 mm
      v 23 mm, respectively). Furthermore, high grade dysplasia was significantly more
      common in flat elevated tumours with central depression or in depressed adenomas
      (35.7%; 5/14) than in flat elevated adenomas (12.8%; 6/47). CONCLUSION: Flat and
      depressed tumours exist in a Western population. Future studies should address
      whether or not chromoendoscopy with video colonoscopy is necessary in the search
      for flat colorectal neoplasms.

PMID- 12235080
TI  - Pk11195, a mitochondrial benzodiazepine receptor antagonist, reduces apoptosis
      threshold in Bcl-X(L) and Mcl-1 expressing human cholangiocarcinoma cells.
AB  - BACKGROUND: Cholangiocarcinoma cells express high levels of the antiapoptotic
      proteins Bcl-X(L) and Mcl-1 and are markedly chemo- and radioresistant.
      Mitochondria have emerged as central players in apoptosis. Antiapoptotic members
      of the Bcl-2 protein family localise to the outer mitochondrial membrane and
      regulate mitochondrial release of apoptogenic proteins. Mitochondrial
      benzodiazepine receptor (mBzR) ligands have been shown to reverse Bcl-2 action
      and facilitate apoptosis. AIM: We evaluated the ability of the mBzR antagonist
      Pk11195 to overcome preapoptotic mitochondrial dysfunction in Egi-1 and Tfk-1,
      two human cholangiocarcinoma cell lines expressing high levels of Bcl-X(L) and
      Mcl-1. MATERIALS AND METHODS: Cells growing in culture were used to perform in
      vitro experiments over 48-96 hours following treatment. The cytotoxic agents used
      were 5 fluorouracil 10 microM and etoposide (Vp16) 10 microM, together with
      ultraviolet and 0.5-1 Gy x ray irradiation with or without 75 microM Pk11195.
      Apoptosis and mitochondrial dysfunction were measured at single cell resolution
      by flow cytometry using the mitochondrial fluorochrome DiOC6(3). Severe combined
      immunodeficient non-obese diabetic (SCID-NOD) mice with subcutaneous xenografts
      using the Egi-1 and Tfk-1 cell lines were treated with etoposide with or without
      addition of Pk11195 over a 72 hour period during which time the xenograft growth
      patterns were monitored. RESULTS: In vitro, the effect of Pk11195 on induction of
      apoptosis in cholangiocarcinoma cells following stimulation by chemotherapy or
      radiotherapy was found to be both time and dose dependent, with Pk11195
      increasing rates of apoptosis by 50-95%. Intraperitoneal administration of
      Pk11195 in combination with Vp16 was found to increase the growth inhibiting
      effects of Vp16 on xenografts during the treatment phase. PK11195 75 microM on
      its own had no intrinsic cytotoxic efficacy. CONCLUSION: This is the first study
      to demonstrate that functional antagonism of coexpressed Bcl-X(L) and Mcl-1
      proteins using the mBzR antagonist Pk11195 can facilitate apoptosis in
      cholangiocarcinoma following chemotherapy and radiotherapy.

PMID- 12235081
TI  - Natural history of primary sclerosing cholangitis and prognostic value of
      cholangiography in a Dutch population.
AB  - BACKGROUND: Median survival of patients with primary sclerosing cholangitis (PSC)
      has been estimated to be 12 years. Cholangiography is the gold standard for
      diagnosis but is rarely used in estimating prognosis. AIMS: To assess the natural
      history of Dutch PSC patients and to evaluate the prognostic value of a
      cholangiographic classification system. PATIENTS: A total of 174 patients with
      established PSC attending a university hospital and three teaching hospitals from
      1970 to 1999. METHODS: Charts were reviewed for validity and time of diagnosis,
      concurrent inflammatory bowel disease, interventions, liver transplantation,
      occurrence of cholangiocarcinoma, and death. Follow up data were obtained from
      the charts and from the attending clinician or family physician. Median follow up
      was 76 months (range 1-300). The earliest available cholangiography was scored
      using a radiological classification system for the severity of sclerosis,
      developed in our institution. Survival curves were computed by the Kaplan-Meier
      method. Cholangiographic staging was used to construct a prognostic model,
      applying Cox proportional hazards analysis. RESULTS: The estimated median
      survival from time of diagnosis to death from liver disease or liver
      transplantation was 18 years. Cholangiocarcinoma was found in 18 (10%) patients.
      Fourteen patients (8%) underwent liver transplantation. Cholangiographic scoring
      was inversely correlated with survival. A combination of intrahepatic and
      extrahepatic scoring, together with age at endoscopic retrograde
      cholangiopancreatography, proved strongly predictive of survival. CONCLUSIONS:
      The observed survival was considerably better than reported in earlier series
      from Sweden, the UK, and the USA. Classification and staging of cholangiographic
      abnormalities has prognostic value.

PMID- 12235082
TI  - Cigarette smoking, appendectomy, and tonsillectomy as risk factors for the
      development of primary sclerosing cholangitis: a case control study.
AB  - BACKGROUND AND AIMS: The strong clinical association between primary sclerosing
      cholangitis (PSC) and ulcerative colitis (UC) suggests common factors in their
      pathogenesis. Smoking, previous appendectomy, and tonsillectomy have been
      associated with a decreased risk of developing UC. In this study, our aim was to
      examine these risk factors in patients with PSC with and without underlying
      inflammatory bowel disease (IBD). METHODS: The smoking habits and history of
      previous appendectomy and/or tonsillectomy of 170 patients with PSC, 41 without
      underlying IBD, 170 patients with UC but normal liver function tests, and 170 age
      and sex matched community controls were obtained by questionnaire. RESULTS: A
      total of 112 PSC patients (66%) had never smoked compared with 66 controls (39%).
      Only 12 PSC patients (7%) were current smokers versus 43 controls (25%). The
      resultant odds ratio of having PSC was 0.17 (95% confidence interval (CI) 0.08
      0.35) among current smokers and 0.33 (95% CI 0.21-0.52) among ever
      (former+current) smokers. Among former smokers, the odds of having PSC were also
      significantly decreased (odds ratio 0.45, 95% CI 0.26-0.73; p<0.05). In the
      subgroup of PSC patients without IBD, only 5% were current smokers versus 26% of
      matched controls, and never smokers were overrepresented (68% v 37%). The rate of
      previous appendectomy was similar in all three study groups (14%, 12%, and 13%)
      but the frequency of tonsillectomy was reduced in the PSC group (21% v 31%;
      p=0.05). CONCLUSION: PSC, like UC, is a disease of non-smokers as the odds of
      having PSC was significantly decreased among current and former smokers. The
      association between non-smoking and PSC was independent of whether the PSC
      patient had underlying IBD. Previous tonsillectomy but not appendectomy may also
      be associated with a decreased risk of PSC but this warrants further study.

PMID- 12235083
TI  - Pancreatic stellate cells contribute to regeneration early after acute
      necrotising pancreatitis in humans.
AB  - BACKGROUND AND AIM: The aim of this study was to systematically analyse the
      pattern of regeneration in human acute pancreatitis by testing whether pancreatic
      stellate cells, their myofibroblastic offspring, and pancreatic ductules are
      involved in the regenerative process. PATIENTS AND METHODS: Between January 1994
      and November 2000, 24 necrosectomy specimens containing vital tissue were
      obtained for pathological examination. Formalin fixed tissue samples were
      routinely processed and immunostained for cytokeratins 7 and 19, smooth muscle
      actin, desmin, Ki-67, and CD68. Pancreatic tissue from organ donors served as
      normal controls. RESULTS: Necrosectomy specimens were obtained between 11 and 41
      days after the onset of symptoms. In vital areas of necrosectomy samples,
      spherical hypercellular spheres consisting of loose vascular connective tissue
      occurred, in part showing duct-like profiles which sprouted from remnant exocrine
      tissue almost perpendicular to the periphery of the spheres. In normal tissue,
      only a few stellate cells and myofibroblasts were present around ducts and
      ductules. In contrast, numerous stellate cells and myofibroblasts were detected
      in the hypercellular regenerative spheres after acute pancreatitis, both being
      situated within the loose tissue and forming compact periductular sheaths.
      Stellate cells/myofibroblasts and ductule cells exhibited increased proliferative
      activity. CONCLUSIONS: Pancreatic stellate cells and their activated
      myofibroblastic offspring may participate in regeneration after acute necrotising
      pancreatitis in humans. Time course studies are needed to further strengthen this
      regeneration concept.

PMID- 12235084
TI  - Extracellular signal regulated kinases are key mediators of mitogenic signals in
      rat pancreatic stellate cells.
AB  - BACKGROUND: Pancreatic stellate cells (PSCs) have been implicated in pancreatic
      fibrosis as they synthesise increased amounts of extracellular matrix proteins in
      response to activation by profibrogenic mediators such as cytokines. AIMS: The
      purpose of this study was to analyse cytokine receptor stimulated signalling
      pathways involved in PSC activation. Using a rat culture model of PSCs, we have
      also tested the potential of the platelet derived growth factor (PDGF) antagonist
      trapidil and PD98059, a specific inhibitor of extracellular signal regulated
      kinase (ERK) activation, to suppress PSC growth. METHODS: Cultured PSCs were
      stimulated with PDGF, and the signal transduction pathways activated in response
      to the mitogen were analysed by immunoblotting, kinase assays, and
      electrophoretic mobility shift assays. Furthermore, comparison of signalling
      cascades activated in PSCs before and after completing transdifferentiation to
      alpha-smooth muscle actin expressing myofibroblasts was performed. Biological
      effects of PDGF, trapidil, and PD98059 were analysed by proliferation assays and
      correlated with molecular effects of the substances. RESULTS: PDGF induced rapid
      activation of Raf-1, ERKs 1 and 2, as well as AP-1 proteins. The transforming
      growth factor beta activated transcription factor Smad2 was found to be
      constitutively phosphorylated in PSCs of different transdifferentiation grades.
      Furthermore, the results indicate a correlation between ERK activities and
      induction of PSC activation. Trapidil efficiently inhibited both PDGF induced ERK
      activation and, in common with PD98059, PSC proliferation. CONCLUSIONS: Our data
      suggest that ERKs play a key role in the regulation of PSC growth and that
      inhibition of the ERK signalling pathway may become a strategy to prevent
      activation of these cells.

PMID- 12235085
TI  - Histological features and HLA class II alleles in hepatitis C virus chronically
      infected patients with persistently normal alanine aminotransferase levels.
AB  - OBJECTIVE: A significant proportion of individuals with chronic hepatitis C virus
      (HCV) infection have persistently normal alanine aminotransferase (ALT) levels.
      Although data are controversial, such patients usually have weaker histological
      damage and a lower progression rate of fibrosis. The aims of this study were: (1)
      to compare demographic, virological, and histological parameters of HCV patients
      with normal ALT values with those of HCV patients with elevated ALT levels; and
      (2) to determine whether HLA class II alleles contribute to the persistence of
      normal ALT levels in HCV patients. PATIENTS AND METHODS: Eighty three patients
      with chronic HCV infection and persistently normal ALT values (group 1) and 233
      patients with chronic HCV infection and elevated ALT levels (group 2) were
      studied. Histological features were expressed using Knodell and Metavir scores.
      HLA DRB1* and DQB1* genotyping was performed using hybridisation with sequence
      specific oligonucleotides after genomic amplification. The kappa2 and Fisher's
      exact tests were used to compare discrete variables and phenotype frequencies
      between the two groups, and Wilcoxon's test was used for continuous variables. A
      multivariate logistic regression model was used to determine which variables
      predicted normal ALT values. RESULTS: ALT levels were correlated with the
      severity of liver damage. In group 1, 93% of patients had an F0 or F1 Metavir
      index of fibrosis compared with 47% of patients in group 2 (p<0.001). A longer
      duration of infection (p<0.001) and increased DRB1*11 phenotype frequency
      (pc=0.03) were observed among patients with normal ALT. The two groups did not
      differ with regard to the mode of contamination or viral genotype. After logistic
      regression, young age (p=0.0008), female sex (p=0.01), long duration of infection
      (p=0.0001), and HLA DRB1*11 (p=0.050) were more strongly associated with
      persistence of normal ALT. CONCLUSIONS: Our study confirms that patients with
      chronic hepatitis C and normal ALT levels have less severe liver disease than
      those with elevated ALT levels. This particular biochemical outcome may be
      explained, at least in part, by host immunogenetic factors such as the presence
      of HLA-DRB1*11.

PMID- 12235086
TI  - Regulation of circulating immune complexes by complement receptor type 1 on
      erythrocytes in chronic viral liver diseases.
AB  - BACKGROUND AND AIM: Complement receptor type 1 (CR1) is a transmembrane protein,
      and human erythrocyte CR1 (E-CR1) is involved in the transport of circulating
      immune complexes (IC) from the circulation to the reticuloendothelial system,
      including the liver and spleen. In chronic viral hepatitis, increased levels of
      IC containing viral particles and an association with various extrahepatic
      manifestations have been reported. However, regulatory mechanisms for IC levels
      are not fully understood. PATIENTS/SUBJECTS AND METHODS: We analysed IC, E-CR1,
      and quantitative polymorphism of the CR1 gene in 149 patients with chronic viral
      liver diseases and in 64 normal blood donors using an enzyme linked immunosorbent
      assay, radioimmunoassay, and polymerase chain reaction-restriction fragment
      length polymorphism, respectively. We also analysed the effect of CR1 gene
      polymorphism on IC binding to E-CR1 using molecular methods. RESULTS: E-CR1
      levels in patients with chronic hepatitis and chronic viral liver diseases as a
      whole correlated inversely with increased levels of IC. Moreover, significantly
      high levels of IC were observed in patients with chronic hepatitis C (CH-C) who
      were homozygous for the E-CR1 low density allele. We also found low levels of E
      CR1 in liver cirrhosis and CH-C but not in CH-B. Low levels of E-CR1 in CH-C were
      observed, even after considering the polymorphism of the CR1 gene. Finally, we
      demonstrated CR1 gene polymorphism dependent binding of hepatitis virus
      containing IC. CONCLUSIONS: Our results emphasise the important role of E-CR1 in
      clearance of IC from the circulation and the acquired, rather than inherited,
      decrease in E-CR1 in chronic viral liver diseases, especially of type C.

PMID- 12235087
TI  - Fatal hepatitis B reactivation following discontinuation of nucleoside analogues
      for chronic hepatitis B.
AB  - BACKGROUND: Nucleoside analogues such as lamivudine for chronic hepatitis B have
      an excellent safety profile while patients are on therapy but reactivation flares
      occur in 19-50% of patients after stopping therapy, some of whom develop liver
      decompensation. AIMS: To describe and report three cases who developed fatal
      hepatitis B reactivation after stopping nucleoside analogue therapy. SUBJECTS AND
      RESULTS: Three patients are described who developed hepatitis B reactivation and
      liver decompensation after stopping therapy. One of the three patients was
      participating in a famciclovir trial and the other two were receiving lamivudine
      therapy for active hepatitis B infection. All three patients had documented
      hepatitis B flares, and all had hepatitis B virus DNA detected at that time. All
      patients developed decompensated liver disease despite one patient having had a
      prior liver biopsy showing absence of cirrhosis. Reintroduction of lamivudine
      therapy failed to halt progression of liver decompensation even after hepatitis B
      virus DNA had been demonstrated to be absent. Sequencing for lamivudine resistant
      mutants in two cases where serum was available failed to show evidence of
      mutations associated with lamivudine resistance. CONCLUSION: Hepatitis B virus
      reactivation, leading to decompensation and death, are possible complications of
      treatment withdrawal and patients should be monitored closely if therapy is
      ceased.

PMID- 12235088
TI  - Collagenous colitis with mucosal tears on endoscopic insufflation: a unique
      presentation.

PMID- 12235090
TI  - Susceptibility to primary sclerosing cholangitis in Brazil is associated with HLA
      DRB1*13 but not with tumour necrosis factor alpha -308 promoter polymorphism.

PMID- 12235091
TI  - Slow transit constipation: more than one disease?

PMID- 12235089
TI  - Hepatitis C and HIV-1 coinfection.
AB  - Hepatitis C virus (HCV) has emerged as the cause of the second major epidemic of
      viral infection after human immunodeficiency virus (HIV) within the past two
      decades, and coinfection of HIV and HCV represents a growing problem for the
      future. This article reviews the current evidence on the epidemiology and
      clinical implications of an interaction between HIV-1 and HCV infection, and the
      current status of the management of patients with combined infection.

PMID- 12235092
TI  - Rectal proliferation and alcohol abuse.

PMID- 12235093
TI  - Surveillance for hepatocellular carcinoma in liver cirrhosis: have programmes
      improved because patients have?

PMID- 12235094
TI  - Motilin agonists and dyspepsia: throwing out the baby with the bath water.

PMID- 12235095
TI  - Causes of obvious jaundice in South West Wales.

PMID- 12235096
TI  - Reducing dyspepsia costs in the community.

PMID- 12235097
TI  - Behaviour of Crohn's disease according to the Vienna classification.

PMID- 12235098
TI  - Malformation syndromes due to inborn errors of cholesterol synthesis.

PMID- 12235099
TI  - Do oxysterols control cholesterol homeostasis?

PMID- 12235100
TI  - The role of cholesterol efflux in regulating the fertilization potential of
      mammalian spermatozoa.

PMID- 12235101
TI  - Hot new therapy for sepsis and the acute respiratory distress syndrome.

PMID- 12235102
TI  - c-Rel delivers a one-two punch in Th1 cell differentiation.

PMID- 12235103
TI  - Cancer therapy and renal injury.

PMID- 12235104
TI  - Do NKT cells control autoimmunity?

PMID- 12235105
TI  - The plastic fetal pituitary.

PMID- 12235106
TI  - Synergistic enhancement of bone formation and healing by stem cell-expressed VEGF
      and bone morphogenetic protein-4.
AB  - We investigated the interaction between angiogenic and osteogenic factors in bone
      formation and bone healing with ex vivo gene therapy using muscle-derived stem
      cells genetically engineered to express human bone morphogenetic protein-4
      (BMP4), VEGF, or VEGF-specific antagonist (soluble Flt1). Our results show that
      although VEGF alone did not improve bone regeneration, it acted synergistically
      with BMP4 to increase recruitment of mesenchymal stem cells, to enhance cell
      survival, and to augment cartilage formation in the early stages of endochondral
      bone formation. These early effects, coupled with accelerated cartilage
      resorption, eventually led to a significant enhancement of bone formation and
      bone healing. The beneficial effect of VEGF on bone healing elicited by BMP4
      depends critically on the ratio of VEGF to BMP4, with an improper ratio leading
      to detrimental effects on bone healing. Finally, we show that soluble Flt1
      inhibits bone formation elicited by BMP4. Thus, VEGF plays an important role in
      bone formation elicited by BMP4, and it can significantly enhance BMP4-elicited
      bone formation and regeneration through multiple mechanisms. This study has
      important implications for the formulation of new strategies to improve bone
      healing through increasing mesenchymal stem cell recruitment and survival, in
      combination with muscle-derived stem cell-based gene therapy.

PMID- 12235107
TI  - A mouse model of human oral-esophageal cancer.
AB  - Squamous cancers of the oral cavity and esophagus are common worldwide, but no
      good genetically based animal model exists. A number of environmental factors as
      well as genetic alterations have been identified in these cancers, yet the
      specific combination of genetic events required for cancer progression remains
      unknown. The Epstein-Barr virus ED-L2 promoter (L2) can be used to target genes
      in a specific fashion to the oral-esophageal squamous epithelium. To that end, we
      generated L2-cyclin D1 (L2D1(+)) mice and crossbred these with p53-deficient
      mice. Whereas L2D1(+) mice exhibit a histologic phenotype of oral-esophageal
      dysplasia, the combination of cyclin D1 expression and p53 deficiency results in
      invasive oral-esophageal cancer. The development of the precancerous lesions was
      significantly reversed by the application of sulindac in the drinking water of
      the L2D1(+)/p53(+/-) mice. Furthermore, cell lines derived from oral epithelia of
      L2D1(+)/p53(+/-) and L2D1(+)/p53(-/-) mice, but not control mice, formed tumors
      in athymic nude mice. These data demonstrate that L2D1(+)/p53(+/-) mice provide a
      well-defined, novel, and faithful model of oral-esophageal cancer, which allows
      for the testing of novel chemopreventive, diagnostic, and therapeutic approaches.

PMID- 12235108
TI  - Circulating levels of IGF-1 directly regulate bone growth and density.
AB  - IGF-1 is a growth-promoting polypeptide that is essential for normal growth and
      development. In serum, the majority of the IGFs exist in a 150-kDa complex
      including the IGF molecule, IGF binding protein 3 (IGFBP-3), and the acid labile
      subunit (ALS). This complex prolongs the half-life of serum IGFs and facilitates
      their endocrine actions. Liver IGF-1-deficient (LID) mice and ALS knockout
      (ALSKO) mice exhibited relatively normal growth and development, despite having
      75% and 65% reductions in serum IGF-1 levels, respectively. Double gene disrupted
      mice were generated by crossing LID+ALSKO mice. These mice exhibited further
      reductions in serum IGF-1 levels and a significant reduction in linear growth.
      The proximal growth plates of the tibiae of LID+ALSKO mice were smaller in total
      height as well as in the height of the proliferative and hypertrophic zones of
      chondrocytes. There was also a 10% decrease in bone mineral density and a greater
      than 35% decrease in periosteal circumference and cortical thickness in these
      mice. IGF-1 treatment for 4 weeks restored the total height of the proximal
      growth plate of the tibia. Thus, the double gene disruption LID+ALSKO mouse model
      demonstrates that a threshold concentration of circulating IGF-1 is necessary for
      normal bone growth and suggests that IGF-1, IGFBP-3, and ALS play a prominent
      role in the pathophysiology of osteoporosis.

PMID- 12235109
TI  - Differential effects of the early and late intrauterine environment on
      corticotrophic cell development.
AB  - The developing embryo and fetus respond to a range of intrauterine stressors, but
      the effect of chronic intrauterine stress on the programmed development of
      pituitary corticotrophs has not been investigated. We have used a pregnant sheep
      model in which the embryonic environment at conception has been surgically
      perturbed by uterine carunclectomy. This procedure results in the development of
      fetuses that either are placentally restricted and chronically hypoxemic or that
      demonstrate compensatory placental growth and maintain normoxemia throughout late
      gestation. We found that uterine carunclectomy resulted in the emergence of a
      population of non-corticotrophin-releasing hormone (non-CRH) target cells that
      secreted high amounts of adrenocorticotrophic hormone (ACTH) in the fetal
      pituitary. This change in corticotroph development was independent of late
      gestation hypoxemia. However, chronic hypoxemia during late gestation (in either
      carunclectomized or non-carunclectomized uterine environments) resulted in a
      reduction in the proportion of ACTH stored in CRH-target. Thus, the early and
      late intrauterine environments differentially program the development of specific
      corticotrophic cell types in the fetal pituitary. These patterns of altered
      corticotroph development are important given the central roles of the hypothalamo
      pituitary-adrenal axis in the fetal adaptive response to intrauterine stress and
      in the early programming of adult disease.

PMID- 12235110
TI  - Testing the NKT cell hypothesis of human IDDM pathogenesis.
AB  - Defects in IL-4-producing CD1d-autoreactive NKT cells have been implicated in
      numerous Th1-mediated autoimmune diseases, including diabetes, multiple
      sclerosis, rheumatoid arthritis, lupus, and systemic sclerosis. Particular
      attention has been focused on autoimmune insulin-dependent diabetes mellitus
      (IDDM) because nonobese diabetic (NOD) mice and humans with IDDM are both
      reported to express severe deficiencies in the frequency and Th2 functions of NKT
      cells. Furthermore, experimental manipulations of the NKT defect in the NOD mouse
      induced corresponding changes in disease. Taken together, these converging
      studies suggested a general role of NKT cells in natural protection against
      destructive autoimmunity. However, in previous reports the identification of NKT
      cells was based on indirect methods. We have now devised a direct, highly
      specific CD1d tetramer-based methodology to test whether humans with IDDM have
      associated NKT cell defects. Surprisingly, although we find marked and stable
      differences in NKT cells between individuals, our study of IDDM patients and
      healthy controls, including discordant twin pairs, demonstrates that NKT cell
      frequency and IL-4 production are conserved during the course of IDDM. These
      results contradict previous conclusions and refute the hypothesis that NKT cell
      defects underlie most autoimmune diseases.

PMID- 12235111
TI  - Adenoviral transfer of HSP-70 into pulmonary epithelium ameliorates experimental
      acute respiratory distress syndrome.
AB  - The acute respiratory distress syndrome (ARDS) provokes three pathologic
      processes: unchecked inflammation, interstitial/alveolar protein accumulation,
      and destruction of pulmonary epithelial cells. The highly conserved heat shock
      protein HSP-70 can limit all three responses but is not appropriately expressed
      in the lungs after cecal ligation and double puncture (2CLP), a clinically
      relevant model of ARDS. We hypothesize that restoring expression of HSP-70 using
      adenovirus-mediated gene therapy will limit pulmonary pathology following 2CLP.
      We administered a vector containing the porcine HSP-70 cDNA driven by a CMV
      promoter (AdHSP) into the lungs of rats subjected to 2CLP or sham operation.
      Administration of AdHSP after either sham operation or 2CLP increased HSP-70
      protein expression in lung tissue, as determined by immunohistochemistry and
      Western blot hybridization. Administration of AdHSP significantly attenuated
      interstitial and alveolar edema and protein exudation and dramatically decreased
      neutrophil accumulation, relative to a control adenovirus. CLP-associated
      mortality at 48 hours was reduced by half. Modulation of HSP-70 production
      reduces pathologic changes and may improve outcome in experimental ARDS.

PMID- 12235112
TI  - Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient
      receiving bone marrow transplantation.
AB  - Duchenne muscular dystrophy (DMD) is a severe progressive muscle-wasting disorder
      caused by mutations in the dystrophin gene. Studies have shown that bone marrow
      cells transplanted into lethally irradiated mdx mice, the mouse model of DMD, can
      become part of skeletal muscle myofibers. Whether human marrow cells also have
      this ability is unknown. Here we report the analysis of muscle biopsies from a
      DMD patient (DMD-BMT1) who received bone marrow transplantation at age 1 year for
      X-linked severe combined immune deficiency and who was diagnosed with DMD at age
      12 years. Analysis of muscle biopsies from DMD-BMT1 revealed the presence of
      donor nuclei within a small number of muscle myofibers (0.5-0.9%). The majority
      of the myofibers produce a truncated, in-frame isoform of dystrophin lacking
      exons 44 and 45 (not wild-type). The presence of bone marrow-derived donor nuclei
      in the muscle of this patient documents the ability of exogenous human bone
      marrow cells to fuse into skeletal muscle and persist up to 13 years after
      transplantation.

PMID- 12235113
TI  - PTEN overexpression suppresses proliferation and differentiation and enhances
      apoptosis of the mouse mammary epithelium.
AB  - The phosphatase PTEN regulates growth, adhesion, and apoptosis, among many other
      cell processes. To investigate its role during mouse mammary gland development,
      we generated MK-PTEN, a transgenic mouse model in which human PTEN is
      overexpressed in ductal and alveolar mammary epithelium during puberty,
      pregnancy, lactation, and involution. No obvious phenotype was observed in
      mammary tissue of pubescent virgin mice. However, MK-PTEN females could not
      lactate normally, and approximately 30% of pups died, with survivors exhibiting
      growth retardation. Transgenic offspring nursed by wild-type foster mothers,
      conversely, developed normally. This phenotype is consistent with a reduced
      number of alveolar epithelial cells due to a decrease in cell proliferation and
      an increase in apoptosis. Using mammary-enriched cDNA microarrays, we identified
      several genes that were preferentially expressed in MK-PTEN mammary tissue,
      including the IGF-binding protein-5 (Igfbp5) gene, and others whose expression
      was reduced, including the genes for c-Jun amino-terminal kinase. Secretory
      epithelial cell differentiation was impaired, as measured by the expression of
      specific milk protein genes. MK-PTEN mice also exhibited a 50% decrease in the
      phosphorylation state of Akt. Taken together, these results suggest that PTEN
      controls mammary gland development and, consequently, lactation.

PMID- 12235114
TI  - Genetic evidence that HNF-1alpha-dependent transcriptional control of HNF-4alpha
      is essential for human pancreatic beta cell function.
AB  - Mutations in the genes encoding hepatocyte nuclear factor 4alpha (HNF-4alpha) and
      HNF-1alpha impair insulin secretion and cause maturity onset diabetes of the
      young (MODY). HNF-4alpha is known to be an essential positive regulator of HNF
      1alpha. More recent data demonstrates that HNF-4alpha expression is dependent on
      HNF-1alpha in mouse pancreatic islets and exocrine cells. This effect is mediated
      by binding of HNF-1alpha to a tissue-specific promoter (P2) located 45.6 kb
      upstream from the previously characterized Hnf4alpha promoter (P1). Here we
      report that the expression of HNF-4alpha in human islets and exocrine cells is
      primarily mediated by the P2 promoter. Furthermore, we describe a G --> A
      mutation in a conserved nucleotide position of the HNF-1alpha binding site of the
      P2 promoter, which cosegregates with MODY. The mutation results in decreased
      affinity for HNF-1alpha, and consequently in reduced HNF-1alpha-dependent
      activation. These findings provide genetic evidence that HNF-1alpha serves as an
      upstream regulator of HNF-4alpha and interacts directly with the P2 promoter in
      human pancreatic cells. Furthermore, they indicate that this regulation is
      essential to maintain normal pancreatic function.

PMID- 12235115
TI  - TNF-alpha mediates chemokine and cytokine expression and renal injury in
      cisplatin nephrotoxicity.
AB  - The purpose of these studies was to examine the role of cytokines in the
      pathogenesis of cisplatin nephrotoxicity. Injection of mice with cisplatin (20
      mg/kg) led to severe renal failure. The expression of cytokines, chemokines, and
      ICAM-1 in kidney was measured by ribonuclease protection assays and RT-PCR. We
      found significant upregulation of TNF-alpha, TGF-beta, RANTES, MIP-2, MCP-1,
      TCA3, IL-1beta, and ICAM-1 in kidneys from cisplatin-treated animals. In
      addition, serum, kidney, and urine levels of TNF-alpha measured by ELISA were
      increased by cisplatin. Inhibitors of TNF-alpha production (GM6001,
      pentoxifylline) and TNF-alpha Ab's reduced serum and kidney TNF-alpha protein
      levels and also blunted the cisplatin-induced increases in TNF-alpha, TGF-beta,
      RANTES, MIP-2, MCP-1, and IL-1beta, but not ICAM-1, mRNA. In addition, the TNF
      alpha inhibitors also ameliorated cisplatin-induced renal dysfunction and reduced
      cisplatin-induced structural damage. Likewise, TNF-alpha-deficient mice were
      resistant to cisplatin nephrotoxicity. These results indicate cisplatin
      nephrotoxicity is characterized by activation of proinflammatory cytokines and
      chemokines. TNF-alpha appears to play a central role in the activation of this
      cytokine response and also in the pathogenesis of cisplatin renal injury.

PMID- 12235116
TI  - Critical roles of c-Rel in autoimmune inflammation and helper T cell
      differentiation.
AB  - Different members of the Rel/NF-kappaB family may play different roles in
      immunity and inflammation. We report here that c-Rel-deficient mice are resistant
      to autoimmune encephalomyelitis and are defective in Th1, but not Th2 responses.
      The Th1 deficiency appears to be caused by selective blockade of IL-12 production
      by c-Rel-deficient antigen-presenting cells, as well as by a complete abrogation
      of IFN-gamma expression in c-Rel-deficient T cells. Interestingly, c-Rel
      deficiency does not affect T-bet expression, suggesting that c-Rel may act
      downstream of T-bet during Th1 cell differentiation. Thus, unlike NF-kappaB1,
      which selectively regulates Th2 cell differentiation, c-Rel is essential for Th1
      cell differentiation and Th1 cell-mediated autoimmune inflammation.

PMID- 12235117
TI  - Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in
      human pancreatic islets.
AB  - In type 2 diabetes, chronic hyperglycemia is suggested to be detrimental to
      pancreatic beta cells, causing impaired insulin secretion. IL-1beta is a
      proinflammatory cytokine acting during the autoimmune process of type 1 diabetes.
      IL-1beta inhibits beta cell function and promotes Fas-triggered apoptosis in part
      by activating the transcription factor NF-kappaB. Recently, we have shown that
      increased glucose concentrations also induce Fas expression and beta cell
      apoptosis in human islets. The aim of the present study was to test the
      hypothesis that IL-1beta may mediate the deleterious effects of high glucose on
      human beta cells. In vitro exposure of islets from nondiabetic organ donors to
      high glucose levels resulted in increased production and release of IL-1beta,
      followed by NF-kappaB activation, Fas upregulation, DNA fragmentation, and
      impaired beta cell function. The IL-1 receptor antagonist protected cultured
      human islets from these deleterious effects. beta cells themselves were
      identified as the islet cellular source of glucose-induced IL-1beta. In vivo, IL
      1beta-producing beta cells were observed in pancreatic sections of type 2
      diabetic patients but not in nondiabetic control subjects. Similarly, IL-1beta
      was induced in beta cells of the gerbil Psammomys obesus during development of
      diabetes. Treatment of the animals with phlorizin normalized plasma glucose and
      prevented beta cell expression of IL-1beta. These findings implicate an
      inflammatory process in the pathogenesis of glucotoxicity in type 2 diabetes and
      identify the IL-1beta/NF-kappaB pathway as a target to preserve beta cell mass
      and function in this condition.

PMID- 12235118
TI  - Craniosynostosis in transgenic mice overexpressing Nell-1.
AB  - Previously, we reported NELL-1 as a novel molecule overexpressed during premature
      cranial suture closure in patients with craniosynostosis (CS), one of the most
      common congenital craniofacial deformities. Here we describe the creation and
      analysis of transgenic mice overexpressing Nell-1. Nell-1 transgenic animals
      exhibited CS-like phenotypes that ranged from simple to compound synostoses.
      Histologically, the osteogenic fronts of abnormally closing/closed sutures in
      these animals revealed calvarial overgrowth and overlap along with increased
      osteoblast differentiation and reduced cell proliferation. Furthermore, anomalies
      were restricted to calvarial bone, despite generalized, non-tissue-specific
      overexpression of Nell-1. In vitro, Nell-1 overexpression accelerated calvarial
      osteoblast differentiation and mineralization under normal culture conditions.
      Moreover, Nell-1 overexpression in osteoblasts was sufficient to promote alkaline
      phosphatase expression and micronodule formation. Conversely, downregulation of
      Nell-1 inhibited osteoblast differentiation in vitro. In summary, Nell-1
      overexpression induced calvarial overgrowth resulting in premature suture closure
      in a rodent model. Nell-1, therefore, has a novel role in CS development, perhaps
      as part of a complex chain of events resulting in premature suture closure. On a
      cellular level, Nell-1 expression may modulate and be both sufficient and
      required for osteoblast differentiation.

PMID- 12235119
TI  - Reorganization of the microtubule array in prophase/prometaphase requires
      cytoplasmic dynein-dependent microtubule transport.
AB  - When mammalian somatic cells enter mitosis, a fundamental reorganization of the
      Mt cytoskeleton occurs that is characterized by the loss of the extensive
      interphase Mt array and the formation of a bipolar mitotic spindle. Microtubules
      in cells stably expressing GFP-alpha-tubulin were directly observed from prophase
      to just after nuclear envelope breakdown (NEBD) in early prometaphase. Our
      results demonstrate a transient stimulation of individual Mt dynamic turnover and
      the formation and inward motion of microtubule bundles in these cells. Motion of
      microtubule bundles was inhibited after antibody-mediated inhibition of
      cytoplasmic dynein/dynactin, but was not inhibited after inhibition of the
      kinesin-related motor Eg5 or myosin II. In metaphase cells, assembly of small
      foci of Mts was detected at sites distant from the spindle; these Mts were also
      moved inward. We propose that cytoplasmic dynein-dependent inward motion of Mts
      functions to remove Mts from the cytoplasm at prophase and from the peripheral
      cytoplasm through metaphase. The data demonstrate that dynamic astral Mts search
      the cytoplasm for other Mts, as well as chromosomes, in mitotic cells.

PMID- 12235120
TI  - Computer simulations reveal motor properties generating stable antiparallel
      microtubule interactions.
AB  - An aster of microtubules is a set of flexible polar filaments with dynamic plus
      ends that irradiate from a common location at which the minus ends of the
      filaments are found. Processive soluble oligomeric motor complexes can bind
      simultaneously to two microtubules, and thus exert forces between two asters.
      Using computer simulations, I have explored systematically the possible steady
      state regimes reached by two asters under the action of various kinds of
      oligomeric motors. As expected, motor complexes can induce the asters to fuse,
      for example when the complexes consist only of minus end-directed motors, or to
      fully separate, when the motors are plus end directed. More surprisingly,
      complexes made of two motors of opposite directionalities can also lead to
      antiparallel interactions between overlapping microtubules that are stable and
      sustained, like those seen in mitotic spindle structures. This suggests that such
      heterocomplexes could have a significant biological role, if they exist in the
      cell.

PMID- 12235121
TI  - Sec16p potentiates the action of COPII proteins to bud transport vesicles.
AB  - SEC16 encodes a 240-kD hydrophilic protein that is required for transport vesicle
      budding from the ER in Saccharomyces cerevisiae. Sec16p is tightly and
      peripherally bound to ER membranes, hence it is not one of the cytosolic proteins
      required to reconstitute transport vesicle budding in a cell-free reaction.
      However, Sec16p is removed from the membrane by salt washes, and using such
      membranes we have reconstituted a vesicle budding reaction dependent on the
      addition of COPII proteins and pure Sec16p. Although COPII vesicle budding is
      promoted by GTP or a nonhydrolyzable analogue, guanylimide diphosphate (GMP-PNP),
      Sec16p stimulation is dependent on GTP in the reaction. Details of coat protein
      assembly and Sec16p-stimulated vesicle budding were explored with synthetic
      liposomes composed of a mixture of lipids, including acidic phospholipids (major
      minor mix), or a simple binary mixture of phosphatidylcholine (PC) and
      phosphatidylethanolamine (PE). Sec16p binds to major-minor mix liposomes and
      facilitates the recruitment of COPII proteins and vesicle budding in a reaction
      that is stimulated by Sar1p and GMP-PNP. Thin-section electron microscopy
      confirms a stimulation of budding profiles produced by incubation of liposomes
      with COPII and Sec16p. Whereas acidic phospholipids in the major-minor mix are
      required to recruit pure Sec16p to liposomes, PC/PE liposomes bind Sar1p-GTP,
      which stimulates the association of Sec16p and Sec23/24p. We propose that Sec16p
      nucleates a Sar1-GTP-dependent initiation of COPII assembly and serves to
      stabilize the coat to premature disassembly after Sar1p hydrolyzes GTP.

PMID- 12235122
TI  - Sphingosine-1-phosphate phosphohydrolase in regulation of sphingolipid metabolism
      and apoptosis.
AB  - Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that
      regulates diverse biological processes by binding to a family of G protein
      coupled receptors or as an intracellular second messenger. Mammalian S1P
      phosphatase (SPP-1), which degrades S1P to terminate its actions, was recently
      cloned based on homology to a lipid phosphohydrolase that regulates the levels of
      phosphorylated sphingoid bases in yeast. Confocal microscopy surprisingly
      revealed that epitope-tagged SPP-1 is intracellular and colocalized with the ER
      marker calnexin. Moreover, SPP-1 activity and protein appeared to be mainly
      enriched in the intracellular membranes with lower expression in the plasma
      membrane. Treatment of SPP-1 transfectants with S1P markedly increased ceramide
      levels, predominantly in the intracellular membranes, diminished survival, and
      enhanced apoptosis. Remarkably, dihydro-S1P, although a good substrate for SPP-1
      in situ, did not cause significant ceramide accumulation or increase apoptosis.
      Ceramide accumulation induced by S1P was completely blocked by fumonisin B1, an
      inhibitor of ceramide synthase, but only partially reduced by myriocin, an
      inhibitor of serine palmitoyltransferase, the first committed step in de novo
      synthesis of ceramide. Furthermore, S1P, but not dihydro-S1P, stimulated
      incorporation of [3H]palmitate, a substrate for both serine palmitoyltransferase
      and ceramide synthase, into C16-ceramide. Collectively, our results suggest that
      SPP-1 functions in an unprecedented manner to regulate sphingolipid biosynthesis
      and is poised to influence cell fate.

PMID- 12235123
TI  - DEDD regulates degradation of intermediate filaments during apoptosis.
AB  - Apoptosis depends critically on regulated cytoskeletal reorganization events in a
      cell. We demonstrate that death effector domain containing DNA binding protein
      (DEDD), a highly conserved and ubiquitous death effector domain containing
      protein, exists predominantly as mono- or diubiquitinated, and that
      diubiquitinated DEDD interacts with both the K8/18 intermediate filament network
      and pro-caspase-3. Early in apoptosis, both cytosolic DEDD and its close
      homologue DEDD2 formed filaments that colocalized with and depended on K8/18 and
      active caspase-3. Subsequently, these filamentous structures collapsed into
      intracellular inclusions that migrated into cytoplasmic blebs and contained DEDD,
      DEDD2, active caspase-3, and caspase-3-cleaved K18 late in apoptosis. Biochemical
      studies further confirmed that DEDD coimmunoprecipitated with both K18 and pro
      caspase-3, and kinetic analyses placed apoptotic DEDD staining prior to caspase-3
      activation and K18 cleavage. In addition, both caspase-3 activation and K18
      cleavage was inhibited by expression of DEDDDeltaNLS1-3, a cytosolic form of DEDD
      that cannot be ubiquitinated. Finally, siRNA mediated DEDD knockdown cells
      exhibited inhibition of staurosporine-induced DNA degradation. Our data suggest
      that DEDD represents a novel scaffold protein that directs the effector caspase-3
      to certain substrates facilitating their ordered degradation during apoptosis.

PMID- 12235124
TI  - A yeast model system for functional analysis of beta-catenin signaling.
AB  - We have developed a novel Saccharomyces cerevisiae model system to dissect the
      molecular events of beta-catenin (beta-cat) signaling. Coexpression of mammalian
      beta-cat with TCF4 or LEF1 results in nuclear accumulation of these proteins and
      a functional complex that activates reporter gene transcription from constructs
      containing leukocyte enhancer factor (LEF)/T cell factor (TCF) response elements.
      Reporter transcription is constitutive, requires expression of both beta-cat and
      TCF4 or LEF1, and is not supported by mutated LEF/TCF binding elements or by TCF4
      or LEF1 mutants. A cytoplasmic domain of E-cadherin or a functional fragment of
      adenomatous polyposis coli (APC) protein (APC-25) complexes with beta-cat,
      reduces beta-cat binding to TCF4, and leads to increased cytoplasmic localization
      of beta-cat and a reduction in reporter activation. Systematic mutation of
      putative nuclear export signal sequences in APC-25 decreases APC-25 binding to
      beta-cat and restores reporter gene transcription. Additional beta-cat signaling
      components, Axin and glycogen synthase kinase 3beta, form a multisubunit complex
      similar to that found in mammalian cells. Coexpression of the F-box protein beta
      transducin repeat-containing protein reduces the stability of beta-cat and
      decreases reporter activation. Thus, we have reconstituted a functional beta-cat
      signal transduction pathway in yeast and show that beta-cat signaling can be
      regulated at multiple levels, including protein subcellular localization, protein
      complex formation, and protein stability.

PMID- 12235125
TI  - Beta-catenin-induced melanoma growth requires the downstream target
      Microphthalmia-associated transcription factor.
AB  - The transcription factor Microphthalmia-associated transcription factor (MITF) is
      a lineage-determination factor, which modulates melanocyte differentiation and
      pigmentation. MITF was recently shown to reside downstream of the canonical Wnt
      pathway during melanocyte differentiation from pluripotent neural crest cells in
      zebrafish as well as in mammalian melanocyte lineage cells. Although expression
      of many melanocytic/pigmentation markers is lost in human melanoma, MITF
      expression remains intact, even in unpigmented tumors, suggesting a role for MITF
      beyond its role in differentiation. A significant fraction of primary human
      melanomas exhibit deregulation (via aberrant nuclear accumulation) of beta
      catenin, leading us to examine its role in melanoma growth and survival. Here, we
      show that beta-catenin is a potent mediator of growth for melanoma cells in a
      manner dependent on its downstream target MITF. Moreover, suppression of melanoma
      clonogenic growth by disruption of beta-catenin-T-cell transcription factor/LEF
      is rescued by constitutive MITF. This rescue occurs largely through a prosurvival
      mechanism. Thus, beta-catenin regulation of MITF expression represents a tissue
      restricted pathway that significantly influences the growth and survival behavior
      of this notoriously treatment-resistant neoplasm.

PMID- 12235126
TI  - Involvement of TRPC in the abnormal calcium influx observed in dystrophic (mdx)
      mouse skeletal muscle fibers.
AB  - Duchenne muscular dystrophy results from the lack of dystrophin, a cytoskeletal
      protein associated with the inner surface membrane, in skeletal muscle. The
      absence of dystrophin induces an abnormal increase of sarcolemmal calcium influx
      through cationic channels in adult skeletal muscle fibers from dystrophic (mdx)
      mice. We observed that the activity of these channels was increased after
      depletion of the stores of calcium with thapsigargin or caffeine. By analogy with
      the situation observed in nonexcitable cells, we therefore hypothesized that
      these store-operated channels could belong to the transient receptor potential
      channel (TRPC) family. We measured the expression of TRPC isoforms in normal and
      mdx adult skeletal muscles fibers, and among the seven known isoforms, five were
      detected (TRPC1, 2, 3, 4, and 6) by RT-PCR. Western blot analysis and
      immunocytochemistry of normal and mdx muscle fibers demonstrated the localization
      of TRPC1, 4, and 6 proteins at the plasma membrane. Therefore, an antisense
      strategy was used to repress these TRPC isoforms. In parallel with the repression
      of the TRPCs, we observed that the occurrence of calcium leak channels was
      decreased to one tenth of its control value (patch-clamp technique), showing the
      involvement of TRPC in the abnormal calcium influx observed in dystrophic fibers.

PMID- 12235127
TI  - Hyaluronan-CD44 interaction hampers migration of osteoclast-like cells by down
      regulating MMP-9.
AB  - Osteoclast (OC) precursors migrate to putative sites of bone resorption to form
      functionally active, multinucleated cells. The preOC FLG 29.1 cells, known to be
      capable of irreversibly differentiating into multinucleated OC-like cells,
      displayed several features of primary OCs, including expression of specific
      integrins and the hyaluronan (HA) receptor CD44. OC-like FLG 29.1 cells adhered
      to and extensively migrated through membranes coated with fibronectin,
      vitronectin, and laminins, but, although strongly binding to HA, totally failed
      to move on this substrate. Moreover, soluble HA strongly inhibited OC-like FLG
      29.1 cell migration on the permissive matrix substrates, and this behavior was
      dependent on its engagement with CD44, as it was fully restored by function
      blocking anti-CD44 antibodies. HA did not modulate the cell-substrate binding
      affinity/avidity nor the expression levels of the corresponding integrins. MMP-9
      was the major secreted metalloproteinase used by OC-like FLG 29.1 cells for
      migration, because this process was strongly inhibited by both TIMP-1 and GM6001,
      as well as by MMP-9-specific antisense oligonucleotides. After HA binding to
      CD44, a strong down-regulation of MMP-9 mRNA and protein was detected. These
      findings highlight a novel role of the HA-CD44 interaction in the context of OC
      like cell motility, suggesting that it may act as a stop signal for bone
      resorbing cells.

PMID- 12235128
TI  - Molecular and functional interaction of the ATP-binding cassette transporter A1
      with Fas-associated death domain protein.
AB  - ATP-binding cassette transporter A1 (ABCA1) is a major regulator of cellular
      cholesterol and phospholipid homeostasis. Its function has not been fully
      characterized and may depend on the association with additional proteins. To
      identify ABCA1-interacting proteins a human liver yeast two-hybrid library was
      screened with the 144 C-terminal amino acids of ABCA1. Fas-associated death
      domain protein (FADD) was identified to bind to ABCA1, and this interaction was
      confirmed by pull-down assays and co-immunoprecipitations. Recombinant expression
      of a dominant negative form of FADD or the C terminus of ABCA1 in the human
      hepatoma cell line HepG2 markedly reduced the transfer of phospholipids to apoA
      I. This indicates that the binding of additional proteins, one of them being full
      length FADD, is required for ABCA1 function. The association of FADD with ABCA1
      provides an unexpected link between high density lipoprotein metabolism and an
      adaptor molecule mainly described in death receptor signal transduction.

PMID- 12235129
TI  - Tryptophan fluorescence reveals conformational changes in the acetylcholine
      binding protein.
AB  - The recent characterization of an acetylcholine binding protein (AChBP) from the
      fresh water snail, Lymnaea stagnalis, shows it to be a structural homolog of the
      extracellular domain of the nicotinic acetylcholine receptor (nAChR). To
      ascertain whether the AChBP exhibits the recognition properties and functional
      states of the nAChR, we have expressed the protein in milligram quantities from a
      synthetic cDNA transfected into human embryonic kidney (HEK) cells. The protein
      secreted into the medium shows a pentameric rosette structure with ligand
      stoichiometry approximating five sites per pentamer. Surprisingly, binding of
      acetylcholine, selective agonists, and antagonists ranging from small alkaloids
      to larger peptides results in substantial quenching of the intrinsic tryptophan
      fluorescence. Using stopped-flow techniques, we demonstrate rapid rates of
      association and dissociation of agonists and slow rates for the alpha
      neurotoxins. Since agonist binding occurs in millisecond time frames, and the
      alpha-neurotoxins may induce a distinct conformational state for the AChBP-toxin
      complex, the snail protein shows many of the properties expected for receptor
      recognition of interacting ligands. Thus, the marked tryptophan quenching not
      only documents the importance of aromatic residues in ligand recognition, but
      establishes that the AChBP will be a useful functional as well as structural
      surrogate of the nicotinic receptor.

PMID- 12235130
TI  - Binding and activation by the zinc cluster transcription factors of Saccharomyces
      cerevisiae. Redefining the UASGABA and its interaction with Uga3p.
AB  - Uga3p, a member of zinc binuclear cluster transcription factor family, is
      required for gamma-aminobutyric acid-dependent transcription of the UGA genes in
      Saccharomyces cerevisiae. Members of this family bind to CGG triplets with the
      spacer region between the triplets being an important specificity determinant. A
      conserved 19-nucleotide activation element in certain UGA gene promoter regions
      contains a CCGN(4)CGG-everted repeat proposed to be the binding site of Uga3p,
      UAS(GABA). The function of conserved nucleotides flanking the everted repeat has
      not been rigorously investigated. The interaction of Uga3p with UAS(GABA) was
      characterized in terms of binding in vitro and transcriptional activation of lacZ
      reporter genes in vivo. Electromobility shift assays using mutant UAS(GABA)
      sequences and heterologously produced full-length Uga3p demonstrated that
      UAS(GABA) consists of two independent Uga3p binding sites. Simultaneous
      occupation of both Uga3p binding sites of UAS(GABA) with high affinity is
      essential for GABA-dependent transcriptional activation in vivo. We present
      evidence that the two Uga3p molecules bound to UAS(GABA) probably interact with
      each other and show that Uga3p((1-124)), previously used for binding studies, is
      not functionally equivalent to the full-length protein with respect to binding in
      vitro. We propose that the Uga3p binding site is an asymmetric site of 5'
      SGCGGNWTTT-3' (S = G or C, W = A, or T and n = no nucleotide or G). However,
      UAS(GABA), is a palindrome containing two asymmetric Uga3p binding sites.

PMID- 12235131
TI  - Identification of specific glycoforms of major histocompatibility complex class I
      heavy chains suggests that class I peptide loading is an adaptation of the
      quality control pathway involving calreticulin and ERp57.
AB  - Glycosylation analysis was used to probe the sequence of events accompanying the
      binding of antigenic peptides to the major histocompatibility complex class I
      heavy chains. Free heavy chains were isolated from the beta(2)-microglobulin
      negative cell line Daudi and from the B-lymphoblastoid cell line Raji. Heavy
      chains were also isolated from Raji cells in multimolecular complexes (peptide
      loading complexes) containing the transporter associated with antigen processing,
      tapasin and ERp57 with and without the lectin-like folding chaperone,
      calreticulin. Calreticulin is a soluble protein that recognizes primarily the
      terminal glucose of Glc(1)Man(7-9)GlcNAc(2) glycans. This paper shows that
      monoglucosylated glycoforms of heavy chain, which exist transiently in the
      endoplasmic reticulum in the initial stages of the glycosylation processing
      pathway, are present in the peptide loading complex. The data are consistent with
      a model in which the release of peptide-loaded major histocompatibility complex
      class I molecules from calreticulin, induced by deglucosylation of the heavy
      chain N-linked glycan, signals the dissociation of the complex. This is
      consistent with the hypothesis that the class I loading process is an adaptation
      of the quality control mechanism involving calreticulin and ERp57.

PMID- 12235132
TI  - Molecular mechanisms for lipopolysaccharide-induced biphasic activation of
      nuclear factor-kappa B (NF-kappa B).
AB  - The nuclear factor-kappaB (NF-kappaB) is an important transcription factor
      necessary for initiating and sustaining inflammatory and immune reactions. The
      inducers of NF-kappaB are well characterized, but the molecular mechanisms
      underlying multiple in vivo NF-kappaB activation processes are poorly understood.
      The injection of lipopolysaccharide resulted in a biphasic activation of NF
      kappaB during the 18-h observation period in various organs of mice. The early
      and late phases of NF-kappaB activation occurred at 0.5-2 h and 8-12 h,
      respectively. Platelet-activating factor, which is released in response to
      lipopolysaccharide injection, was responsible for the activation of the early
      phase of NF-kappaB. The early NF-kappaB activity led to the induction of
      proinflammatory cytokines, tumor necrosis factor (TNF), and interleukin (IL)
      1beta, which are known to be efficient inducers of NF-kappaB. Using the TNF
      knockout and IL-1 receptor knockout mice, we found that TNF and IL-1beta had a
      role in the second phase activation of NF-kappaB. These cytokines did promote the
      synthesis of platelet-activating factor, which in turn induced the secondary
      activation of NF-kappaB. These observations describe a novel autoregulatory
      molecular mechanism for the biphasic activation of NF-kappaB.

PMID- 12235133
TI  - Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate actin
      polymerization and filopodium formation. Wiskott-Aldrich Syndrome protein.
AB  - Wiskott-Aldrich Syndrome protein (WASp) is a key regulator of the Arp2/3 complex
      and the actin cytoskeleton in hematopoietic cells. WASp is capable of forming an
      auto-inhibited conformation, which can be disrupted by binding of Cdc42 and
      phosphatidylinositol 4,5-bisphosphate, leading to its activation. Stimulation of
      the collagen receptor on platelets and crosslinking the B-cell receptor induce
      tyrosine phosphorylation of WASp. Here we show that the Src family kinase Hck
      induces phosphorylation of WASp-Tyr(291) independently of Cdc42 and that this
      causes a shift in the mobility of WASp upon SDS-PAGE. A phospho-mimicking mutant,
      WASp-Y291E, exhibited an enhanced ability to stimulate actin polymerization in a
      cell-free system and when microinjected into primary macrophages induced
      extensive filopodium formation with greater efficiency than wild-type WASp or a
      Y291F mutant. We propose that phosphorylation of Tyr(291) directly regulates WASp
      function.

PMID- 12235134
TI  - A novel sterol 14alpha-demethylase/ferredoxin fusion protein (MCCYP51FX) from
      Methylococcus capsulatus represents a new class of the cytochrome P450
      superfamily.
AB  - Sterol 14alpha-demethylase encoded by CYP51 is a member of the cytochrome P450
      (CYP) superfamily of enzymes and has been shown to have an essential role in
      sterol biosynthesis in eukaryotes, with orthologues recently being described in
      some bacteria. Examination of the genome sequence data for the proteobacterium
      Methylococcus capsulatus, a bacterial species known to produce sterol, revealed
      the presence of a single CYP with strong homology to CYP51, particularly to a
      form in Mycobacterium tuberculosis. This M. capsulatus CYP51 protein represents a
      new class of CYP consisting of the CYP domain naturally fused to a ferredoxin
      domain at the C terminus via an alanine-rich linker. Expression of the M.
      capsulatus MCCYP51FX fusion in Escherichia coli yielded a P450, which, when
      purified to homogeneity, had the predicted molecular mass approximately 62 kDa on
      SDS/PAGE and bound lanosterol as a putative substrate. Sterol 14alpha-demethylase
      activity was shown (0.24 nmol of lanosterol metabolized per minute per nanomole
      of MCCYP51FX fusion) by gas chromatography/mass spectrometry with the activity
      dependent upon the presence of ferredoxin reductase and NADPH. Our unique
      findings describe a new class of naturally existing cytochrome P450, which will
      provide pivotal information for CYP structure/function in general.

PMID- 12235135
TI  - Modulation of the hepatitis C virus RNA-dependent RNA polymerase activity by the
      non-structural (NS) 3 helicase and the NS4B membrane protein.
AB  - The hepatitis C virus (HCV) nonstructural protein 5B (NS5B) is believed to be the
      central catalytic enzyme responsible for HCV replication but there are many
      unanswered questions about how its activity is controlled. In this study we
      reveal that two other HCV proteins, NS3 (a protease/helicase) and NS4B (a
      hydrophobic protein of unknown function), physically and functionally interact
      with the NS5B polymerase. We describe a new procedure for generating highly pure
      NS4B, and use this protein in biochemical studies together with NS5B and NS3. To
      study the functional effects of the protein-protein interactions, we have
      developed an in vitro replication assay using the natural noncoding 3' regions of
      the respective positive ((+)-3'-untranslated region) and negative ((-)-3'
      terminal region) RNA strands of the HCV genome. Our studies show that NS3
      dramatically modulates template recognition by NS5B and changes the synthetic
      products generated by this enzyme. The use of an NTPase-deficient mutant form of
      NS3 demonstrates that the NTPase activity (and thus helicase activity) of this
      protein is specifically required for these effects. Moreover, NS4B is found to be
      a negative regulator of the NS3-NS5B replication complex. Overall, these results
      reveal that NS3, NS4B, and NS5B can interact to form a regulatory complex that
      could feature in the process of HCV replication.

PMID- 12235136
TI  - Bi-functional, substrate mimicking RNA inhibits MSK1-mediated cAMP-response
      element-binding protein phosphorylation and reveals magnesium ion-dependent
      conformational changes of the kinase.
AB  - The design of specific inhibitors for protein kinases is an important step toward
      elucidation of intracellular signal transduction pathways and to guide drug
      discovery programs. We devised a model approach to generate specific, competitive
      kinase inhibitors by isolating substrate mimics containing two independent
      binding sites with an anti-idiotype strategy from combinatorial RNA libraries. As
      a general test for the ability to generate highly specific kinase inhibitors, we
      selected the transcription factor cAMP-response element-binding protein (CREB)
      that is phosphorylated on the same serine residue by the protein kinase MSK1 as
      well as by RSK1. The sequences and structures of these kinases are very similar,
      about 60% of their amino acids are identical. Nevertheless, we can demonstrate
      that the selected RNA inhibitors inhibit specifically CREB phosphorylation by
      MSK1 but do not affect CREB phosphorylation by RSK1. The inhibitors interact
      preferentially with the inactive form of MSK1. Furthermore, we demonstrate that
      RNA ligands can be conformation-specific probes, and this feature allowed us to
      describe magnesium ion-dependent conformational changes of MSK1 upon activation.

PMID- 12235137
TI  - A- and B-utrophin have different expression patterns and are differentially up
      regulated in mdx muscle.
AB  - Duchenne muscular dystrophy (DMD) is a fatal childhood disease caused by
      mutations that abolish the expression of dystrophin in muscle. Utrophin is a
      paralogue of dystrophin and can functionally replace it in skeletal muscle. A
      method to induce utrophin up-regulation in muscle should therefore be
      therapeutically useful in DMD. We have previously shown that there are two full
      length utrophin mRNA species: A and B. Here we describe the generation and
      characterization of antibodies specific to A- and B-utrophin. We show that both
      mRNA isoforms are translated into full-length proteins, which have very different
      expression patterns. B-utrophin is expressed in vascular endothelial cells; A
      utrophin is expressed at the neuromuscular junction, choroid plexus, pia mater,
      and renal glomerulus. We have analyzed the expression of A- and B-utrophin
      protein and RNA in dystrophin-deficient tissues. We conclude that (i) the
      previously described expression patterns of utrophin represent a composite of A-
      and B-utrophin, (ii) A- but not B-utrophin is up-regulated in dystrophin
      deficient striated muscle, and (iii) this up-regulation occurs post
      transcriptionally with an additional transcriptional component in skeletal
      muscle. These results have important implications for understanding the biology
      of utrophin and are crucial for future studies aiming to effect its therapeutic
      up-regulation in DMD patients.

PMID- 12235139
TI  - Hsp31, the Escherichia coli yedU gene product, is a molecular chaperone whose
      activity is inhibited by ATP at high temperatures.
AB  - The Escherichia coli chromosome contains several uncharacterized heat-inducible
      loci that may encode novel molecular chaperones or proteases. Here we show that
      the 31-kDa product of the yedU gene is an efficient homodimeric molecular
      chaperone that is conserved in a number of pathogenic eubacteria and fungi. Heat
      shock protein (Hsp) 31 relies on temperature-driven conformational changes to
      expose structured hydrophobic domains that are likely responsible for substrate
      binding. Complementing the function of refolding, remodeling, and holding
      chaperones, Hsp 31 preferentially interacts with early unfolding intermediates
      and rapidly releases them in an active form after transfer to low temperatures.
      Although Hsp 31 does not appear to exhibit intrinsic ATPase activity, binding of
      ATP at high temperatures restricts the size or availability of the substrate
      binding site, thereby modulating chaperone activity. The possible role of ATP in
      coordinating the function of the cellular complement of molecular chaperones is
      discussed.

PMID- 12235138
TI  - Interaction of HCF-1 with a cellular nuclear export factor.
AB  - HCF-1 is a cellular protein required by VP16 to activate the herpes simplex virus
      (HSV) immediate-early genes. VP16 is a component of the viral tegument and, after
      release into the cell, binds to HCF-1 and translocates to the nucleus to form a
      complex with the POU domain protein Oct-1 and a VP16-responsive DNA sequence.
      This VP16-induced complex boosts transcription of the viral immediate-early genes
      and initiates lytic replication. In uninfected cells, HCF-1 functions as a
      coactivator for the cellular transcription factors LZIP and GABP and also plays
      an essential role in cell proliferation. VP16 and LZIP share a tetrapeptide HCF
      binding motif recognized by the beta-propeller domain of HCF-1. Here we describe
      a new cellular HCF-1 beta-propeller domain binding protein, termed HPIP, which
      contains a functional HCF-binding motif and a leucine-rich nuclear export
      sequence. We show that HPIP shuttles between the nucleus and cytoplasm in a CRM1
      dependent manner and that overexpression of HPIP leads to accumulation of HCF-1
      in the cytoplasm. These data suggest that HPIP regulates HCF-1 activity by
      modulating its subcellular localization. Furthermore, HPIP-mediated export may
      provide the pool of cytoplasmic HCF-1 required for import of virion-derived VP16
      into the nucleus.

PMID- 12235140
TI  - Potassium-evoked glutamate release liberates arachidonic acid from cortical
      neurons.
AB  - Brain cells in situ contain low concentrations of free polyunsaturated fatty
      acids such as arachidonic acid (AA) that are released following pathological
      insults. As a large rise in extracellular [K(+)] accompanies cerebral ischemia,
      we explored whether this was a stimulus for cellular AA release employing a
      murine mixed cortical cell culture preparation radiolabeled with AA. Elevating
      the [K(+)](o) from 5 to 52 mm induced a time-dependent increase in [(3)H]AA
      release, which reached a plateau after 15 min. Removal of [Ca(2+)](o) or addition
      of CdCl(2) (100 microm) diminished the net high K(+)-induced AA release, as did
      treatment of the cultures with tetanus toxin (300 ng/ml) to block endogenous
      neurotransmitter release. Pharmacological antagonism of both ionotropic and
      metabotropic glutamate receptors completely prevented high K(+)-evoked AA
      release, indicating that glutamate was the neurotransmitter in question. Addition
      of exogenous glutamate mimicked precisely the characteristics of AA release that
      followed increases in [K(+)](o). Finally, glutamate and AA were released solely
      from neurons as tetanus toxin did not cleave astrocytic synaptobrevin-2, nor was
      AA released from pure astrocyte cultures using the same stimuli that were
      effective in mixed cultures. Taken in toto, our data are consistent with the
      following scenario: high [K(+)](o) depolarizes neurons, causing an influx of
      Ca(2+) via voltage-gated Ca(2+) channels. This Ca(2+) influx stimulates the
      release of glutamate into the synaptic cleft, where it activates postsynaptic
      glutamate receptors. Events likely converge on the activation of a phospholipase
      A(2) family member and possibly the enzymes diacylglycerol and monoacylglycerol
      lipases to yield free AA.

PMID- 12235141
TI  - A human sex hormone-binding globulin isoform accumulates in the acrosome during
      spermatogenesis.
AB  - Human sex hormone-binding globulin (SHBG) binds estradiol and testosterone with
      high affinity. Plasma SHBG is produced by hepatocytes, but the human SHBG gene is
      also expressed in the testis. Little is known about SHBG gene expression in the
      human testis, but human SHBG transcripts accumulate in a spermatogenic stage
      dependent manner in the testes of mice containing an 11-kb human SHBG transgene.
      We have now found that human SHBG transcripts containing an alternative exon 1
      sequence are located specifically in the testicular germ cells of these
      transgenic mice, whereas murine SHBG transcripts are confined to Sertoli cells.
      In addition, we have detected immunoreactive human SHBG in the acrosome during
      all stages of spermiogenesis in mice containing an 11-kb human SHBG transgene.
      Western blots of germ cell extracts from these transgenic mice and from human
      sperm indicate that the immunoreactive human SHBG in the acrosome composes
      electrophoretic variants, which are 3-5 kDa smaller than the major
      electrophoretic isoforms of human SHBG in the blood. This apparent size
      difference is due in part to differences in glycosylation of plasma and acrosomal
      SHBG isoforms. The function of the human SHBG isoform in the acrosome is unknown,
      but it binds steroid ligands with high affinity. This is the first demonstration
      that human SHBG transcripts encode an SHBG isoform that remains within a cellular
      compartment.

PMID- 12235142
TI  - Interactions of STAT3 with caveolin-1 and heat shock protein 90 in plasma
      membrane raft and cytosolic complexes. Preservation of cytokine signaling during
      fever.
AB  - Interleukin-6 (IL-6) initiates STAT3 signaling in plasma membrane rafts with the
      subsequent transit of Tyr-phosphorylated STAT3 (PY-STAT3) through the cytoplasmic
      compartment to the nucleus in association with accessory proteins. We initially
      identified caveolin-1 (cav-1) as a candidate STAT3-associated accessory protein
      due to its co-localization with STAT3 and PY-STAT3 in flotation raft fractions,
      and heat shock protein 90 (HSP90) due to its inclusion in cytosolic STAT3
      containing 200-400-kDa complexes. Subsequent immunomagnetic bead pullout assays
      showed that STAT3, PY-STAT3, cav-1, and HSP90 interacted in plasma membrane and
      cytoplasmic complexes derived from uninduced and stimulated Hep3B cells. This was
      a general property of STAT3 in that these interactions were also observed in
      alveolar epithelial type II-like cells, lung fibroblasts, and pulmonary arterial
      endothelial cells. Exposure of Hep3B cells to the raft disrupter methyl-beta
      cyclodextrin for 1-10 min followed by IL-6 stimulation for 15 min preferentially
      inhibited the appearance of PY-STAT3 in the cav-1-enriched sedimentable
      cytoplasmic fraction, suggesting that these complexes may represent a trafficking
      intermediate immediately downstream from the raft. Because IL-6 is known to
      function in the body in the context of fever, the possibility that HSP90 may help
      preserve IL-6-induced STAT3 signaling at elevated temperature was investigated.
      Geldanamycin, an HSP90 inhibitor, markedly inhibited IL-6-stimulated STAT3
      signaling in Hep3B hepatocytes cultured overnight at 39.5 degrees C as evaluated
      by DNA-shift assays, trafficking of PY-STAT3 to the nucleus, cross-precipitation
      of HSP90 by anti-STAT3 polyclonal antibody, and reporter/luciferase construct
      experiments. Taken together, the data show that IL-6/raft/STAT3 signaling is a
      chaperoned pathway that involves cav-1 and HSP90 as accessory proteins and
      suggest a mechanism for the preservation of this signaling during fever.

PMID- 12235143
TI  - Determinants for removal and degradation of transit peptides of chloroplast
      precursor proteins.
AB  - The stromal processing peptidase (SPP) cleaves a large diversity of chloroplast
      precursor proteins, removing an N-terminal transit peptide. We predicted
      previously that this key step of the import pathway is mediated by features of
      the transit peptide that determine precursor binding and cleavage followed by
      transit peptide conversion to a degradable substrate. Here we performed
      competition experiments using synthesized oligopeptides of the transit peptide of
      ferredoxin precursor to investigate the mechanism of these processes. We found
      that binding and processing of ferredoxin precursor depend on specific
      interactions of SPP with the region consisting of the C-terminal 12 residues of
      the transit peptide. Analysis of four other precursors suggests that processing
      depends on the same region, although their transit peptides are highly divergent
      in primary sequence and length. Upon processing, SPP terminates its interaction
      with the transit peptide by a second cleavage, converting it to a subfragment
      form. From the competition experiments we deduce that SPP releases a subfragment
      consisting of the transit peptide without its original C terminus. Interestingly,
      examination of the ATP-dependent metallopeptidase activity responsible for
      degradation of transit peptide subfragments suggests that it may recognize other
      unrelated peptides and, hence, act separately from SPP as a novel stromal
      oligopeptidase.

PMID- 12235144
TI  - Neuronal differentiation-dependent expression of the disialic acid epitope on
      CD166 and its involvement in neurite formation in Neuro2A cells.
AB  - We previously demonstrated that alpha2,8-linked disialic acid (diSia) residues
      occur in several glycoproteins of mammalian brains (Sato, C., Fukuoka, H., Ohta,
      K., Matsuda, T., Koshino, R., Kobayashi, K., Troy, F. A., II, and Kitajima, K.
      (2000) J. Biol. Chem. 275, 15422-15431). The role of the diSia epitope on these
      glycoproteins is not known, whereas the importance of the diSia epitope on
      glycolipids is well documented in neurite formation. In this study, we
      demonstrated that the diSia epitope (Neu5Acalpha2 --> 8Neu5Acalpha2 --> 3Gal) on
      glycoproteins, but not on glycolipids, is involved in neurite formation in a
      mouse neuroblastoma cell line, Neuro2A, based on the following lines of evidence.
      First, the amount of diSia epitope on glycoproteins increased during retinoic
      acid-induced neurite formation. Second, retinoic acid treatment primarily
      increased the diSia epitope on a 100-kDa glycoprotein. We identified this protein
      as CD166 (SC1), an immunoglobulin superfamily cell adhesion molecule involved in
      neurite extension. Third, a monoclonal antibody against the diSia epitope
      specifically inhibited neurite formation. We also demonstrated that alpha2,8
      sialyltransferase III mRNA expression increased 1.7-fold after the induction of
      neurite formation, suggesting that alpha2,8-sialyltransferase III is responsible
      for formation of the diSia epitope on CD166.

PMID- 12235145
TI  - The tyrosine phosphatase PRL-1 localizes to the endoplasmic reticulum and the
      mitotic spindle and is required for normal mitosis.
AB  - PRL-1 is one of three closely related protein-tyrosine phosphatases, which are
      characterized by C-terminal farnesylation. Recent reports suggest that they are
      involved in the regulation of cell proliferation and transformation. However,
      their biological function has not yet been determined. Here we show that PRL-1
      mRNA is overexpressed in a number of human tumor cell lines, including HeLa
      cells. Using immunofluorescence we studied the subcellular localization of
      endogenous PRL-1, and our results demonstrate that PRL-1 exhibits cell cycle
      dependent localization; in non-mitotic HeLa cells, PRL-1 is localized to the
      endoplasmic reticulum in a farnesylation-dependent manner. In mitotic cells PRL-1
      relocalizes to the centrosomes and the spindle apparatus, proximal to the
      centrosomes, in a farnesylation-independent manner. Conditional expression of a
      catalytic domain mutant in HeLa cells results in a delay in the progression of
      cells through mitosis but has no effect on other phases of the cell cycle.
      Further, expression of a farnesylation site PRL-1 mutant results in mitotic
      defects, characterized by chromosomal bridges in anaphase and lagging
      chromosomes, without affecting spindle checkpoint function. Together, these
      results suggest that PRL-1 function is regulated in a cell cycle-dependent manner
      and implicate PRL-1 in regulating progression through mitosis, possibly by
      modulating spindle dynamics.

PMID- 12235146
TI  - Role of the C-terminal extensions of alpha-crystallins. Swapping the C-terminal
      extension of alpha-crystallin to alphaB-crystallin results in enhanced chaperone
      activity.
AB  - Several small heat shock proteins contain a well conserved alpha-crystallin
      domain, flanked by an N-terminal domain and a C-terminal extension, both of which
      vary in length and sequence. The structural and functional role of the C-terminal
      extension of small heat shock proteins, particularly of alphaA- and alphaB
      crystallins, is not well understood. We have swapped the C-terminal extensions
      between alphaA- and alphaB-crystallins and generated two novel chimeric proteins,
      alphaABc and alphaBAc. We have investigated the domain-swapped chimeras for
      structural and functional alterations. We have used thermal and non-thermal
      models of protein aggregation and found that the chimeric alphaB with the C
      terminal extension of alphaA-crystallin, alphaBAc, exhibits dramatically enhanced
      chaperone-like activity. Interestingly, however, the chimeric alphaA with the C
      terminal extension of alphaB-crystallin, alphaABc, has almost lost its activity.
      Pyrene solubilization and bis-1-anilino-8-naphthalenesulfonate binding studies
      show that alphaBAc exhibits more solvent-exposed hydrophobic pockets than alphaA,
      alphaB, or alphaABc. Significant tertiary structural changes are revealed by
      tryptophan fluorescence and near-UV CD studies upon swapping the C-terminal
      extensions. The far-UV CD spectrum of alphaBAc differs from that of alphaB
      crystallin whereas that of alphaABc overlaps with that of alphaA-crystallin. Gel
      filtration chromatography shows alteration in the size of the proteins upon
      swapping the C-terminal extensions. Our study demonstrates that the unstructured
      C-terminal extensions play a crucial role in the structure and chaperone
      activity, in addition to generally believed electrostatic "solubilizer" function.

PMID- 12235147
TI  - RNA interference reveals a requirement for myocyte enhancer factor 2A in activity
      dependent neuronal survival.
AB  - RNA interference (RNAi) provides a powerful method of gene silencing in
      eukaryotic cells, including proliferating mammalian cells. However, the utility
      of RNAi as a method of gene knock-down in primary postmitotic mammalian neurons
      remained unknown. Here, we asked if RNAi might be utilized to allow the
      assessment of the biological function of a specific gene in the nervous system.
      We employed a U6 promoter-driven DNA template approach to induce hairpin RNA
      triggered RNAi to characterize the role of the transcription factor myocyte
      enhancer factor 2A (MEF2A) in the neuronal activity-dependent survival of granule
      neurons of the developing rat cerebellum. We found that the expression of MEF2A
      hairpin RNAs leads to the efficient and specific inhibition of endogenous MEF2A
      protein expression in primary cerebellar granule neurons. We also found that RNAi
      of MEF2A reduces significantly MEF2 response element-mediated transcription in
      granule neurons and inhibits activity-dependent granule neuron survival. Taken
      together, our RNAi experiments have revealed that MEF2A plays a critical role in
      activity-dependent neuronal survival. In addition, our findings indicate that
      RNAi does operate in postmitotic mammalian neurons and thus offers a rapid
      genetic method of studying gene function in the development and function of the
      mammalian nervous system.

PMID- 12235148
TI  - Characterization of the second type of human beta-galactoside alpha 2,6
      sialyltransferase (ST6Gal II), which sialylates Galbeta 1,4GlcNAc structures on
      oligosaccharides preferentially. Genomic analysis of human sialyltransferase
      genes.
AB  - A novel member of the human beta-galactoside alpha2,6-sialyltransferase (ST6Gal)
      family, designated ST6Gal II, was identified by BLAST analysis of expressed
      sequence tags and genomic sequences. The sequence of ST6Gal II encoded a protein
      of 529 amino acids, and it showed 48.9% amino acid sequence identity with human
      ST6Gal I. Recombinant ST6Gal II exhibited alpha2,6-sialyltransferase activity
      toward oligosaccharides that have the Galbeta1,4GlcNAc sequence at the
      nonreducing end of their carbohydrate groups, but it exhibited relatively low and
      no activities toward some glycoproteins and glycolipids, respectively. It is
      concluded that ST6Gal II is an oligosaccharide-specific enzyme compared with
      ST6Gal I, which exhibits broad substrate specificities, and is mainly involved in
      the synthesis of sialyloligosaccharides. The expression of the ST6Gal II gene was
      significantly detected by reverse transcription PCR in small intestine, colon,
      and fetal brain, whereas the ST6Gal I gene was ubiquitously expressed, and its
      expression levels were much higher than those of the ST6Gal II gene. The ST6Gal I
      gene was also expressed in all tumors examined, but no expression was observed
      for the ST6Gal II gene in these tumors. The ST6Gal II gene is located on
      chromosome 2 (2q11.2-q12.1), and it spans over 85 kb of human genomic DNA
      consisting of at least eight exons and shares a similar genomic structure with
      the ST6Gal I gene. In this paper, we have shown that ST6Gal I, which has been
      known as the sole member of the ST6Gal family, also has the counterpart enzyme
      (ST6Gal II) like other sialyltransferases.

PMID- 12235149
TI  - A physical and functional interaction between yeast Pol4 and Dnl4-Lif1 links DNA
      synthesis and ligation in nonhomologous end joining.
AB  - Genetic studies have implicated the Saccharomyces cerevisiae POL4 gene product in
      the repair of DNA double-strand breaks by nonhomologous end joining. Here we show
      that Pol4 preferentially catalyzes DNA synthesis on small gaps formed by the
      alignment of linear duplex DNA molecules with complementary ends, a DNA substrate
      specificity that is compatible with its predicted role in the repair of DNA
      double-strand breaks. Pol4 also interacts directly with the Dnl4 subunit of the
      Dnl4-Lif1 complex via its N-terminal BRCT domain. This interaction stimulates the
      DNA synthesis activity of Pol4 and, to a lesser extent, the DNA joining activity
      of Dnl4-Lif1. Notably, the joining of DNA substrates that require the combined
      action of Pol4 and Dnl4-Lif1 is much more efficient than the joining of similar
      DNA substrates that require only ligation. Thus, the physical and functional
      interactions between Pol4 and Dnl4-Lif1 provide a molecular mechanism for both
      the recruitment of Pol4 to in vivo DNA double-strand breaks and the coupling of
      the gap filling DNA synthesis and DNA joining reactions that complete the
      microhomology-mediated pathway of nonhomologous end joining.

PMID- 12235150
TI  - Structural and functional consequences of mutating cysteine residues in the amino
      terminus of human multidrug resistance-associated protein 1.
AB  - Multidrug resistance-associated protein 1 (MRP1) is a member of the ATP-binding
      cassette membrane transport superfamily and is responsible for multidrug
      resistance in cancer cells. Currently, there are nine known human MRPs. Distinct
      from many other members of the ATP-binding cassette superfamily, human MRP1 and
      four other MRPs have an additional membrane-spanning domain (MSD) with a putative
      extracellular amino terminus. The functional significance of this additional MSD
      (MSD1) is currently unknown. To understand the role of MSD1 in human MRP1
      structure and function, we studied the amino-terminal 33 amino acids. We found
      that the amino terminus of human MRP1 has two cysteine residues (Cys(7) and
      Cys(32)) that are conserved among the five human MRPs that have MSD1. Mutation
      analyses of the two cysteines in human MRP1 revealed that the Cys(7) residue is
      critical for the MRP1-mediated drug resistance and leukotriene C(4) transport
      activity. On the other hand, mutation of Cys(32) reduced only moderately the MRP1
      function. The effect of Cys(7) mutation on MRP1 activity appears to be due to the
      5-7-fold decrease in the maximal transport rate V(max). We also found that
      mutation of Cys(7) changed the amino-terminal conformation of MRP1. This
      conformational change is likely responsible for the decrease in V(max) of LTC(4)
      transport mediated by the mutant MRP1. Based on these studies, we conclude that
      the amino terminus of human MRP1 is important and that the Cys(7) residue plays a
      critical role in maintaining the proper structure and function of human MRP1.

PMID- 12235151
TI  - Eph B4 receptor signaling mediates endothelial cell migration and proliferation
      via the phosphatidylinositol 3-kinase pathway.
AB  - The goals of this study were 2-fold: 1) to determine whether stimulation of Eph
      B4 receptors promotes microvascular endothelial cell migration and/or
      proliferation, and 2) to elucidate signaling pathways involved in these
      responses. The human endothelial cells used possessed abundant Eph B4 receptors
      with no endogenous ephrin B2 expression. Stimulation of these receptors with
      ephrin B2/Fc chimera resulted in dose- and time-dependent phosphorylation of Akt.
      These responses were inhibited by LY294002 and ML-9, blockers of
      phosphatidylinositol 3-kinase (PI3K) and Akt, respectively. Eph B4 receptor
      activation increased proliferation by 38%, which was prevented by prior blockade
      with LY294002, ML-9, and inhibitors of protein kinase G (KT5823) and MEK
      (PD98059). Nitrite levels increased over 170% after Eph B4 stimulation,
      indicating increased nitric oxide production. Signaling of endothelial cell
      proliferation appears to be mediated by a PI3K/Akt/endothelial nitric-oxide
      synthase/protein kinase G/mitogen-activated protein kinase cascade. Stimulation
      with ephrin B2 also increased migration by 63% versus controls. This effect was
      inhibited by blockade with PP2 (Src inhibitor), LY294002 or ML-9 but was
      unaffected by the PKG and MEK blockers. Eph B4 receptor stimulation increased
      activation of both matrix metalloproteinase-2 and -9. The results from these
      studies indicate that Eph B4 stimulates migration and proliferation and may play
      a role in angiogenesis.

PMID- 12235152
TI  - Crystal structure of rat heme oxygenase-1 in complex with heme bound to azide.
      Implication for regiospecific hydroxylation of heme at the alpha-meso carbon.
AB  - Heme oxygenase (HO) catalyzes physiological heme degradation consisting of three
      sequential oxidation steps that use dioxygen molecules and reducing equivalents.
      We determined the crystal structure of rat HO-1 in complex with heme and azide
      (HO-heme-N(3)(-)) at 1.9-A resolution. The azide, whose terminal nitrogen atom is
      coordinated to the ferric heme iron, is situated nearly parallel to the heme
      plane, and its other end is directed toward the alpha-meso position of the heme.
      Based on resonance Raman spectroscopic analysis of HO-heme bound to dioxygen,
      this parallel coordination mode suggests that the azide is an analog of dioxygen.
      The azide is surrounded by residues of the distal F-helix with only the direction
      to the alpha-meso carbon being open. This indicates that regiospecific
      oxygenation of the heme is primarily caused by the steric constraint between the
      dioxygen bound to heme and the F-helix. The azide interacts with Asp-140, Arg
      136, and Thr-135 through a hydrogen bond network involving five water molecules
      on the distal side of the heme. This network, also present in HO-heme, may
      function in dioxygen activation in the first hydroxylation step. From the
      orientation of azide in HO-heme-N(3)(-), the dioxygen or hydroperoxide bound to
      HO-heme, the active oxygen species of the first reaction, is inferred to have a
      similar orientation suitable for a direct attack on the alpha-meso carbon.

PMID- 12235153
TI  - Characterization of an antagonist interleukin-6 dimer by stable isotope labeling,
      cross-linking, and mass spectrometry.
AB  - The homodimeric form of a recombinant cytokine interleukin-6 (IL-6(D)) is known
      to antagonize IL-6 signaling. In this study, spatially proximal residues between
      IL-6 chains in IL-6(D) were identified using a method for specific recognition of
      intermolecular cross-linked peptides. Our strategy involved mixing 1:1 (15)N
      labeled and unlabeled ((14)N) protein to form a mixture of isotopically labeled
      and unlabeled homodimers, which was chemically cross-linked. This cross-linked IL
      6(D) was subjected to proteolysis by trypsin and the generated peptides were
      analyzed by electrospray ionization time-of-flight mass spectrometry (MS).
      Molecular ions from cross-linked peptides of intermolecular origin are labeled
      with [(15)N/(15)N] + [(15)N/(14)N] + [(14)N/(15)N] + [(14)N/(14)N] yielding
      readily identified triplet/quadruplet MS peaks. All other peptide species are
      labeled with [(15)N] + [(14)N] yielding doublet peaks. Intermolecular cross
      linked peptides were identified by MS, and cross-linked residues were identified.
      This intermolecular cross-link detection method, which we have designated "mixed
      isotope cross-linking" MIX may have more general application to protein-protein
      interaction studies. The pattern of proximal residues found was consistent with
      IL-6(D) having a domain-swapped fold similar to IL-10 and interferon-gamma. This
      fold implies that IL-6(D)-mediated antagonism of IL-6 signaling is caused by
      obstruction of cooperative gp130 binding on IL-6(D), rather than direct blocking
      of gp-130-binding sites on IL-6(D).

PMID- 12235154
TI  - Tyrosinase-catalyzed oxidation of fluorophenols.
AB  - The activity of the type 3 copper enzyme tyrosinase toward 2-, 3-, and 4
      fluorophenol was studied by kinetic methods and (1)H and (19)F NMR spectroscopy.
      Whereas 3- and 4-fluorophenol react with tyrosinase to give products that undergo
      a rapid polymerization process, 2-fluorophenol is not reactive and actually acts
      as a competitive inhibitor in the enzymatic oxidation of 3,4
      dihydroxyphenylalanine (L-dopa). The tyrosinase-mediated polymerization of 3- and
      4-fluorophenols has been studied in detail. It proceeds through a phenolic
      coupling pathway in which the common reactive fluoroquinone, produced
      stereospecifically by tyrosinase, eliminates an inorganic fluorine ion. The
      enzymatic reaction studied as a function of substrate concentration shows a
      prominent lag that is completely depleted in the presence of L-dopa. The kinetic
      parameters of the reactions can be correlated to the electronic and steric
      effects of the fluorine substituent position. Whereas the fluorine electron
      withdrawing effect appears to control the binding of the substrates (K(m) for 3-
      and 4-fluorophenols and K(I) for 2-fluorophenol), the k(cat) parameters do not
      follow the expected trend, indicating that in the transition state some
      additional steric effect rules the reactivity.

PMID- 12235155
TI  - The components of the Saccharomyces cerevisiae mannosyltransferase complex M-Pol
      I have distinct functions in mannan synthesis.
AB  - The yeast Saccharomyces cerevisiae processes N-linked glycans in the Golgi
      apparatus in two different ways. Whereas most of the proteins of internal
      membranes receive a simple core-type structure, a long branched polymer termed
      mannan is attached to the glycans of many of the proteins destined for the cell
      wall. The first step in mannan synthesis is the initiation and extension of an
      alpha-1,6-linked polymannose backbone. This requires the sequential action of two
      enzyme complexes, mannan polymerases (M-Pol) I and II. M-Pol I contains the
      proteins Mnn9p and Van1p, although the stoichiometry and individual contributions
      to enzyme action are unclear. We report here that the two proteins are each
      present as a single copy in the complex. Both proteins contain a DXD motif found
      in the active site of many glycosyltransferases, and mutations in this motif in
      Mnn9p or Van1p reveal that both proteins contribute to mannose polymerization.
      However, the effects of these mutations on both the in vivo and in vitro activity
      are distinct, suggesting that the two proteins may have different roles in the
      complex. Finally, we show that a simple glycoprotein based on hen egg lysozyme
      can be used as a substrate for modification by purified M-Pol I in vitro.

PMID- 12235156
TI  - Crystal structure of the heterodimeric complex of the adaptor, ClpS, with the N
      domain of the AAA+ chaperone, ClpA.
AB  - Substrate selectivity and proteolytic activity for the E. coli ATP-dependent
      protease, ClpAP, is modulated by an adaptor protein, ClpS. ClpS binds to ClpA,
      the regulatory component of the ClpAP complex. We report the crystal structure of
      ClpS in complex with the isolated N-terminal domain of ClpA in two different
      crystal forms at 2.3- and 3.3-A resolution. The ClpS structure forms an
      alpha/beta-sandwich and is topologically analogous to the C-terminal domain of
      the ribosomal protein L7/L12. ClpS contacts two surfaces on the N-terminal domain
      in both crystal forms; the more extensive interface was shown to be favored in
      solution by protease protection experiments. The N-terminal 20 residues of ClpS
      are not visible in the crystal structures; the removal of the first 17 residues
      produces ClpSDeltaN, which binds to the ClpA N-domain but no longer inhibits ClpA
      activity. A zinc binding site involving two His and one Glu residue was
      identified crystallographically in the N-terminal domain of ClpA. In a model of
      ClpS bound to hexameric ClpA, ClpS is oriented with its N terminus directed
      toward the distal surface of ClpA, suggesting that the N-terminal region of ClpS
      may affect productive substrate interactions at the apical surface or substrate
      entry into the ClpA translocation channel.

PMID- 12235157
TI  - Intracellular calcium and myosin isoform transitions. Calcineurin and calcium
      calmodulin kinase pathways regulate preferential activation of the IIa myosin
      heavy chain promoter.
AB  - Intracellular calcium levels can have profound effects on muscle biology via
      alterations in gene expression. In particular, intracellular calcium levels
      increase during muscle activation and are thought to underlie fast-to-slow shifts
      in muscle gene expression. In the present work, we determined that increased
      intracellular calcium has a significant effect on the activity of the adult fast
      myosin heavy chain (MyHC) promoters in the order of MyHC IIa>> IId/x > IIb. We
      have identified the pathways by which the calcium signal mediates increased
      activation of the MyHC IIa promoter. Inhibition of calcineurin or calcium
      calmodulin kinase greatly attenuates ionophore-induced activation of the MyHC IIa
      promoter, whereas protein kinase C inhibitors have no effect. Inhibition and
      overexpression studies with members of the mitogen-activated protein kinase
      family reveal roles for MEK1/MEK2 and MEKK1, but not p38 or phosphatidylinositol
      3-kinase. Downstream mediators of these effects are the activities of the MEF-2
      and NFAT transcription factors, whose binding sites in the MyHC IIa promoter are
      required for calcium-induced activation of the MyHC IIa promoter.

PMID- 12235158
TI  - Crystal structure of Tritrichomonas foetus inosine monophosphate dehydrogenase in
      complex with the inhibitor ribavirin monophosphate reveals a catalysis-dependent
      ion-binding site.
AB  - Inosine monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step in
      GMP biosynthesis. The resulting intracellular pool of guanine nucleotides is of
      great importance to all cells for use in DNA and RNA synthesis, metabolism, and
      signal transduction. The enzyme binds IMP and the cofactor NAD(+) in random
      order, IMP is converted to XMP, NAD(+) is reduced to NADH, and finally, NADH and
      then XMP are released sequentially. XMP is subsequently converted into GMP by GMP
      synthetase. Drugs that decrease GMP synthesis by inhibiting IMPDH have been shown
      to have antiproliferative as well as antiviral activity. Several drugs are in use
      that target the substrate- or cofactor-binding site; however, due to differences
      between the mammalian and microbial isoforms, most drugs are far less effective
      against the microbial form of the enzyme than the mammalian form. The high
      resolution crystal structures of the protozoan parasite Tritrichomonas foetus
      IMPDH complexed with the inhibitor ribavirin monophosphate as well as
      monophosphate together with a second inhibitor, mycophenolic acid, are presented
      here. These structures reveal an active site cation identified previously only in
      the Chinese hamster IMPDH structure with covalently bound IMP. This cation was
      not found previously in apo IMPDH, IMPDH in complex with XMP, or covalently bound
      inhibitor, indicating that the cation-binding site may be catalysis-dependent. A
      comparison of T. foetus IMPDH with the Chinese hamster and Streptococcus pyogenes
      structures reveals differences in the active site loop architecture, which
      contributes to differences in cation binding during the catalytic sequence and
      the kinetic rates between bacterial, protozoan, and mammalian enzymes.
      Exploitation of these differences may lead to novel inhibitors, which favor the
      microbial form of the enzyme.

PMID- 12235159
TI  - Human papilloma virus 16 E6 oncoprotein inhibits retinoic X receptor-mediated
      transactivation by targeting human ADA3 coactivator.
AB  - The expression of human papillomavirus (HPV) E6 oncoprotein is causally linked to
      high-risk HPV-associated human cancers. We have recently isolated hADA3, the
      human homologue of yeast transcriptional co-activator yADA3, as a novel E6
      target. Human ADA3 binds to the high-risk (cancer-associated) but not the low
      risk HPV E6 proteins and to immortalization-competent but not to immortalization
      defective HPV16 E6 mutants, suggesting a role for the perturbation of hADA3
      function in E6-mediated oncogenesis. We demonstrate here that hADA3 directly
      binds to the retinoic X receptor (RXR)alpha in vitro and in vivo. Using chromatin
      immunoprecipitation, we show that hADA3 is part of activator complexes bound to
      the native RXR response elements within the promoter of the cyclin-dependent
      kinase inhibitor gene p21. We show that hADA3 enhances the RXR(alpha)-mediated
      sequence-specific transactivation of retinoid target genes, cellular retinoic
      acid-binding protein II and p21. Significantly, we demonstrate that E6 inhibits
      the RXR(alpha)-mediated transactivation of target genes, implying that
      perturbation of RXR-mediated transactivation by E6 could contribute to HPV
      oncogenesis.

PMID- 12235160
TI  - N-terminal residues regulate the catalytic efficiency of the Hsp90 ATPase cycle.
AB  - Hsp90 is an abundant molecular chaperone involved in a variety of cellular
      processes ranging from signal transduction to viral replication. The function of
      Hsp90 has been shown to be dependent on its ability to hydrolyze ATP, and in
      vitro studies suggest that the dimeric nature of Hsp90 is critical for this
      activity. ATP binding occurs at the N-terminal domains of the Hsp90 dimer,
      whereas the main dimerization site resides in the very C-terminal domain. ATP
      hydrolysis is performed in a series of conformational changes. These include the
      association of the two N-terminal domains, which has been shown to stimulate the
      hydrolysis reaction. In this study, we set out to identify regions in the N
      terminal domain that are important for this interaction. We show that N-terminal
      deletion variants of Hsp90 are severely impaired in their ability to hydrolyze
      ATP. However, nucleotide binding of these constructs is similar to that of the
      wild type protein. Heterodimers of the Hsp90 deletion mutants with wild type
      protein showed that the first 24 amino acids play a crucial role during the
      ATPase reaction, because their deletion abolishes the trans-activation between
      the two N-terminal domains. We propose that the turnover rate of Hsp90 is
      decisively controlled by intermolecular interactions between the N-terminal
      domains.

PMID- 12235161
TI  - The Kruppel-like factor Zf9 and proteins in the Sp1 family regulate the
      expression of HSP47, a collagen-specific molecular chaperone.
AB  - In several cells and tissues the synthesis of HSP47, a collagen-specific
      molecular chaperone in the endoplasmic reticulum, is closely correlated with the
      synthesis of collagen. We previously reported that the Sp1 binding site at -210
      bp in the promoter region and the first and second introns are required for the
      tissue-specific expression of HSP47 in transgenic mice (Hirata, H., Yamamura, I.,
      Yasuda, K., Kobayashi, A., Tada, N., Suzuki, M., Hirayoshi, K., Hosokawa, N., and
      Nagata, K. (1999) J. Biol. Chem. 274, 35703-35710). Here, we analyze how these
      introns influence the transcriptional regulation of the hsp47 gene in BALB/c 3T3
      cells, which produce high levels of HSP47. In vitro promoter analysis using a
      luciferase reporter and gel mobility shift analysis revealed that two cis-acting
      elements in the first and second introns, BS5-B and EP7-D, respectively, are
      required for the activation of hsp47 in BALB/c 3T3 cells. Several members of the
      Kruppel-like factor (KLF) family of proteins were identified as BS5-B-binding
      proteins by yeast one-hybrid analysis using these elements as baits. One of these
      proteins, KLF-6/Zf9, binds to the BS5-B element and activates expression of the
      reporter construct when transfected into cells. Chromatin immunoprecipitation
      assay analysis revealed that the endogenous KLF-6/Zf9 binds the BS5-B elements
      that contain the CACCC motif, which is a consensus recognition sequence for other
      proteins in the KLF family. We also showed that BS5-B and EP7-D are bound by two
      members of the Sp1 family, Sp2 and Sp3. These results suggest that at least three
      sequences are required for the constitutive expression of hsp47 in BALB/c 3T3
      cells: the -210 bp Sp1 binding site, the BS5-B element in the first intron, and
      the EP7-D element in the second intron. We suggest that KLF proteins regulate the
      transcription of hsp47 by binding the BS5-B element in cooperation with Sp2
      and/or Sp3.

PMID- 12235162
TI  - Crystal structure of brain pyridoxal kinase, a novel member of the ribokinase
      superfamily.
AB  - The three-dimensional structures of brain pyridoxal kinase and its complex with
      the nucleotide ATP have been elucidated in the dimeric form at 2.1 and 2.6 A,
      respectively. Results have shown that pyridoxal kinase, as an enzyme obeying
      random sequential kinetics in catalysis, does not possess a lid shape structure
      common to all kinases in the ribokinase superfamily. This finding has been shown
      to be in line with the condition that pyridoxal kinase binds substrates with
      variable sizes of chemical groups at position 4 of vitamin B(6) and its
      derivatives. In addition, the enzyme contains a 12-residue peptide loop in the
      active site for the prevention of premature hydrolysis of ATP. Conserved amino
      acid residues Asp(118) and Tyr(127) in the peptide loop could be moved to a
      position covering the nucleotide after its binding so that its chance to
      hydrolyze in the aqueous environment of the active site was reduced. With respect
      to the evolutionary trend of kinase enzymes, the existence of this loop in
      pyridoxal kinase could be classified as an independent category in the ribokinase
      superfamily according to the structural feature found and mechanism followed in
      catalysis.

PMID- 12235163
TI  - The active principle of garlic at atomic resolution.
AB  - Despite the fact that many cultures around the world value and utilize garlic as
      a fundamental component of their cuisine as well as of their medicine cabinets,
      relatively little is known about the plant's protein configuration that is
      responsible for the specific properties of garlic. Here, we report the three
      dimensional structure of the garlic enzyme alliinase at 1.5 A resolution.
      Alliinase constitutes the major protein component in garlic bulbs, and it is able
      to cleave carbon-sulfur bonds. The active enzyme is a pyridoxal-5'-phosphate
      dependent homodimeric glycoprotein and belongs to the class I family of pyridoxal
      5'-phosphate-dependent enzymes. In addition, it contains a novel epidermal growth
      factor-like domain that makes it unique among all pyridoxal-5'-phosphate
      dependent enzymes.

PMID- 12235164
TI  - Electrophile response element-mediated induction of the cystine/glutamate
      exchange transporter gene expression.
AB  - In mammalian cultured cells, the cystine/glutamate exchange transport mediated by
      system x(c)- is important to maintain intracellular GSH levels. System x(c)-
      consists of two protein components, xCT and the heavy chain of 4F2 antigen. The
      activity of system x(c)- is induced by various stimuli, including electrophilic
      agents like diethyl maleate. In the present study, we have investigated the
      mechanism of the transcriptional regulation of xCT mRNA by diethyl maleate. The
      xCT gene consisted of twelve exons and sequence analysis identified four
      electrophile response element (EpRE)-like sequences between -230 and -1 in the 5'
      flanking region, designated EpRE-1 to EpRE-4. To identify sequences mediating the
      constitutive and induced expression of xCT, a series of 5'-deletion mutants
      created from the 5'-flanking region were cloned into a luciferase reproter vector
      and transfected into BHK21 cells. The 5'-deletion analysis revealed that the
      sequence between -116 and -82 is essential for the basal expression and the
      sequence between -226 and -116 containing EpRE-1 is essential in response to
      diethyl maleate. Mutational analysis demonstrated that EpRE-1 is critically
      involved in the response to diethyl maleate. Other stress agents like arsenite,
      cadmium, and hydroquinone seemed to induce system x(c)- activity via the same
      sequence. Furthermore, the experiments using the mouse embryonic fibroblasts
      derived from the Nrf2-deficient mice revealed that the induction of xCT gene by
      electrophilic agents is mediated by Nrf2. EpRE occurs in a broad spectrum of
      genes for the proteins that are involved in the defense against xenobiotics and
      regulates their expression. The present results have demonstrated that xCT is a
      novel member of this protein family.

PMID- 12235165
TI  - Fibroblast growth factor-2 induces Lef/Tcf-dependent transcription in human
      endothelial cells.
AB  - Lef/Tcf proteins belong to a family of architectural transcription factors that
      control developmental processes and play an important role in oncogenesis.
      Classical activators of Lef/Tcf-dependent transcription comprise the Wnt family
      of proteins, which translocate beta-catenin into the nucleus and allow the
      formation of transactivation-competent Lef/Tcf-beta-catenin complexes. Here we
      show that in human endothelial cells fibroblast growth factor-2 (FGF-2) reduces
      GSK-3 activity and augments nuclear levels of beta-catenin. FGF-2 induced Lef/Tcf
      dependent transcription of a cyclin D1-luciferase construct. Gel shift assays
      revealed binding of Tcf-4 as the only Lef/Tcf family member and of beta-catenin
      to the Lef/Tcf site in the cyclin D1 promoter. Cotransfection with a dominant
      negative Tcf-4 construct inhibited the FGF-2-induced cyclin D1 promoter activity.
      Overexpression of an uninhibitable GSK-3beta mutant resulted in partial
      inhibition of FGF-2-mediated cyclin D1 induction. The importance for cyclin D1 in
      FGF-2-induced angiogenesis in vivo is shown in cyclin D1(-/-) mice, where FGF-2
      induced new vessel formation was significantly reduced compared with FGF-2
      induced angiogenesis in cyclin D1(+/+) mice. In conclusion, FGF-2 is a novel
      modulator of Lef/Tcf-beta-catenin signaling in endothelial cells, suggesting that
      angiogenic properties of FGF-2 are at least in part mediated by Lef/Tcf-beta
      catenin activation.

PMID- 12235167
TI  - Hepatic lipase: a pro- or anti-atherogenic protein?
AB  - Hepatic lipase (HL) plays a role in the metabolism of pro- and anti-atherogenic
      lipoproteins affecting their plasma level and composition. However, there is
      controversy regarding whether HL accelerates or retards atherosclerosis. Its
      effects on different lipoprotein classes show that, potentially, HL may promote
      as well as decrease atherogenesis. Studies in animals with genetically modulated
      HL expression show that it depends on the model used whether HL acts pro- or anti
      atherogenic. In humans, HL activity seems to correlate inversely with
      atherosclerosis in (familial) hypercholesterolemia, and positively in
      hypertriglyceridemia. In normolipidemia, HL activity is weakly associated with
      coronary artery disease (CAD). Genetically low or absent HL activity is usually
      associated with increased CAD risk, especially if plasma lipid transport is
      impaired due to other factors. Since HL promotes the uptake of lipoproteins and
      lipoprotein-associated lipids, HL may affect intracellular lipid content. We
      hypothesize that the prime role of HL is to maintain, in concert with other
      factors (e.g., lipoprotein receptors), intracellular lipid homeostasis. This, and
      the uncertainties about its impact on human atherosclerosis, makes it difficult
      to predict whether HL is a suitable target for intervention to lower CAD risk.
      First, the physiological meaning of changes in HL activity under different
      conditions should be clarified.

PMID- 12235168
TI  - Metabolic origins and clinical significance of LDL heterogeneity.
AB  - LDLs in humans comprise multiple distinct subspecies that differ in their
      metabolic behavior and pathologic roles. Metabolic turnover studies suggest that
      this heterogeneity results from multiple pathways, including catabolism of
      different VLDL and IDL precursors, metabolic remodeling, and direct production. A
      common lipoprotein profile designated atherogenic lipoprotein phenotype is
      characterized by a predominance of small dense LDL particles. Multiple features
      of this phenotype, including increased levels of triglyceride rich lipoprotein
      remnants and IDLs, reduced levels of HDL and an association with insulin
      resistance, contribute to increased risk for coronary heart disease compared with
      individuals with a predominance of larger LDL. Increased atherogenic potential of
      small dense LDL is suggested by greater propensity for transport into the
      subendothelial space, increased binding to arterial proteoglycans, and
      susceptibility to oxidative modification. Large LDL particles also can be
      associated with increased coronary disease risk, particularly in the setting of
      normal or low triglyceride levels. Like small LDL, large LDL exhibits reduced LDL
      receptor affinity compared with intermediate sized LDL. Future delineation of the
      determinants of heterogeneity of LDL and other apoB-containing lipoproteins may
      contribute to improved identification and management of patients at high risk for
      atherosclerotic disease.

PMID- 12235169
TI  - FATP1 channels exogenous FA into 1,2,3-triacyl-sn-glycerol and down-regulates
      sphingomyelin and cholesterol metabolism in growing 293 cells.
AB  - Biosynthesis of lipids was investigated in growing 293 cells stably expressing
      fatty acid (FA) transport protein 1 (FATP1), a bifunctional polypeptide with FA
      transport as well as fatty acyl-CoA synthetase activity. In short-term (30 s)
      incubations, FA uptake was increased in FATP1 expressing cells (C8 cells)
      compared with the vector (as determined by BODIPY 3823 staining and radioactive
      FA uptake). In long-term (4 h) incubations, incorporation of [(14)C]acetate,
      [3H]oleic acid, or [(14)C]lignoceric acid into 1,2,3-triacyl-sn-glycerol (TG) was
      elevated in C8 cells compared with vector, whereas incorporation of radiolabel
      into glycerophospholipids was unaltered. The increase in TG biosynthesis
      correlated with an increase in 1,2-diacyl-sn-glycerol acyltransferase activity in
      C8 cells compared with vector. In contrast, incorporation of [(14)C]acetate into
      sphingomyelin (SM) and cholesterol, and [3H]oleic acid or [(14)C]lignoceric acid
      into SM was reduced due to a reduction in de novo biosynthesis of these lipids in
      C8 cells compared with vector. The results indicate that exogenously supplied
      FAs, and their subsequently produced acyl-CoAs, are preferentially channeled by
      an FATP1 linked mechanism into the TG biosynthetic pathway and that such
      internalized lipids down-regulate de novo SM and cholesterol metabolism in
      actively growing 293 cells.

PMID- 12235170
TI  - Uptake of long-chain fatty acids in HepG2 cells involves caveolae: analysis of a
      novel pathway.
AB  - We investigated the role of caveolae in uptake and intracellular trafficking of
      long chain fatty acids (LCFA) in HepG2 human hepatoma cells. The uptake of
      [(3)H]oleic acid and [(3)H]stearic acid into HepG2 cells was measured by
      radioactive assays and internalization of the non-metabolizable fluorescent fatty
      acid 12-(N-methyl)-N-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino] (12-NBD) stearate
      into single HepG2 cells was semi-quantitatively assessed by laser scanning
      microscopy. The initial rate of [(3)H]oleic acid uptake (V(0)) in HepG2 cells
      exhibited saturable transport kinetics with increasing concentrations of free
      oleic acid (V(max) 854 +/- 46 pmol mg protein(-1) min(-1), K(m) 100 +/- 14
      nmol/l). While inhibition of clathrin coated pits did not influence LCFA uptake
      in HepG2, inhibition of caveolae formation by filipin III, cyclodextrin, and
      caveolin-1 antisense oligonucleotides resulted in reduction of [(3)H]oleic acid
      uptake by 54%, 45%, and 23%, respectively. Furthermore, filipin III inhibited the
      uptake of [(3)H]stearic acid and its fluorescent derivative 12-NBD stearate by
      44% and 50%, respectively. Transfection studies with alpha-caveolin
      1/cyanofluorescent protein chimeras showed significant colocalization of caveolae
      and internalized 12-NBD stearate. In conclusion, these data suggest a significant
      role for caveolae mediated uptake and intracellular trafficking of LCFA in HepG2
      cells.

PMID- 12235171
TI  - Dietary trans-10,cis-12 conjugated linoleic acid induces hyperinsulinemia and
      fatty liver in the mouse.
AB  - Conjugated linoleic acids (CLA) are a class of positional, geometric, conjugated
      dienoic isomers of linoleic acid (LA). Dietary CLA supplementation results in a
      dramatic decrease in body fat mass in mice, but also causes considerable liver
      steatosis. However, little is known of the molecular mechanisms leading to
      hepatomegaly. Although c9,t11- and t10,c12-CLA isomers are found in similar
      proportions in commercial preparations, the respective roles of these two
      molecules in liver enlargement has not been studied. We show here that mice fed a
      diet enriched in t10,c12-CLA (0.4% w/w) for 4 weeks developed lipoatrophy,
      hyperinsulinemia, and fatty liver, whereas diets enriched in c9,t11-CLA and LA
      had no significant effect. In the liver, dietary t10,c12-CLA triggered the
      ectopic production of peroxisome proliferator-activated receptor gamma
      (PPARgamma), adipocyte lipid-binding protein and fatty acid transporter mRNAs and
      induced expression of the sterol responsive element-binding protein-1a and fatty
      acid synthase genes. In vitro transactivation assays demonstrated that t10,c12-
      and c9,t11-CLA were equally efficient at activating PPARalpha, beta/delta, and
      gamma and inhibiting liver-X-receptor. Thus, the specific effect of t10,c12-CLA
      is unlikely to result from direct interaction with these nuclear receptors.
      Instead, t10,c12-CLA-induced hyperinsulinemia may trigger liver steatosis, by
      inducing both fatty acid uptake and lipogenesis.

PMID- 12235172
TI  - Promoting export of macrophage cholesterol: the physiological role of a major
      acute-phase protein, serum amyloid A 2.1.
AB  - We show that murine macrophages that have ingested cell membranes as a source of
      cholesterol exhibit a marked increase in acyl-CoA:cholesterol acyl transferase
      (ACAT) activity. Exposure of these macrophages to acute-phase high-density
      lipoprotein (HDL) results in a marked reduction of ACAT and enhancement of
      cholesteryl ester hydrolase (CEH) activities, phenomena not seen with native HDL.
      These complementary but opposite effects of acute-phase HDL on the two enzyme
      systems that regulate the balance between esterified (storage) cholesterol and
      unesterified (transportable) cholesterol are shown to reside with serum amyloid A
      (SAA) 2.1, an acute-phase apolipoprotein of HDL whose plasma concentration
      increases 500- to 1,000-fold within 24 h of acute tissue injury. Mild trypsin
      treatment of acute-phase HDL almost completely abolishes the apolipoprotein
      mediated effects on the cholesteryl ester cycle in cholesterol-laden macrophages.
      The physiological effect of SAA2.1 on macrophage cholesterol is to shift it into
      a transportable state enhancing its rate of export, which we confirm in tissue
      culture and in vivo. The export process is shown to be coupled to the ATP binding
      cassette transport system. Our findings integrate previous isolated observations
      about SAA into the sphere of cholesterol transport, establish a function for a
      major acute-phase protein, and offer a novel approach to mobilizing macrophage
      cholesterol at sites of atherogenesis.

PMID- 12235173
TI  - Overexpression of SR-BI by adenoviral vector promotes clearance of apoA-I, but
      not apoB, in human apoB transgenic mice.
AB  - Scavenger receptor BI (SR-BI) is a multi-ligand lipoprotein receptor that
      mediates selective lipid uptake from HDL, and plays a central role in hepatic HDL
      metabolism. In this report, we investigated the extent to which SR-BI selective
      lipid uptake contributes to LDL metabolism. As has been reported for human LDL,
      mouse SR-BI expressed in transfected cells mediated selective lipid uptake from
      mouse LDL. However, LDL-cholesteryl oleoyl ester (CE) transfer relative to LDL-CE
      bound to the cell surface (fractional transfer) was approximately 18-fold lower
      compared with HDL-CE. Adenoviral vector-mediated SR-BI overexpression in livers
      of human apoB transgenic mice ( approximately 10-fold increased expression)
      reduced plasma HDL-cholesterol (HDL-C) and apolipoprotein (apo)A-I concentrations
      to nearly undetectable levels 3 days after adenovirus infusion. Increased hepatic
      SR-BI expression resulted in only a modest depletion in LDL-C that was restricted
      to large LDL particles, and no change in steady-state concentrations of human
      apoB. Kinetic studies showed a 19% increase in the clearance rate of LDL-CE in
      mice with increased SR-BI expression, but no change in LDL apolipoprotein
      clearance. Quantification of hepatic uptake of LDL-CE and LDL-apolipoprotein
      showed selective uptake of LDL-CE in livers of human apo B transgenic mice.
      However, such uptake was not significantly increased in mice over-expressing SR
      BI. We conclude that SR-BI-mediated selective uptake from LDL plays a minor role
      in LDL metabolism in vivo.

PMID- 12235174
TI  - Interactions of acyl carnitines with model membranes: a (13)C-NMR study.
AB  - Esterification of fatty acids with the small polar molecule carnitine is a
      required step for the regulated flow of fatty acids into mitochondrial inner
      matrix. We have studied the interactions of acyl carnitines (ACs) with model
      membranes [egg yolk phosphatidylcholine (PC) vesicles] by (13)C-nuclear magnetic
      resonance (NMR) spectroscopy. Using AC with (13)C-enrichment of the carbonyl
      carbon of the acyl chain, we detected NMR signals from AC on the inside and
      outside leaflets of the bilayer of small unilamellar vesicles prepared by
      cosonication of PC and AC. However, when AC was added to the outside of pre
      formed PC vesicles, only the signal for AC bound to the outer leaflet was
      observed, even after hours at equilibrium. The extremely slow transmembrane
      diffusion ("flip-flop") is consistent with the zwitterionic nature of the
      carnitine head group and the known requirement of transport proteins for movement
      of ACs through the mitochondrial membrane. The partitioning of ACs (8-18 carbons)
      between water and PC vesicles was studied by monitoring the [(13)C]carbonyl
      chemical shift of ACs as a function of pH and concentration of vesicles.
      Significant partitioning into the water phase was detected for ACs with chain
      lengths of 12 carbons or less. The effect of ACs on the integrity of the bilayer
      was examined in vesicles with up to 25 mol% myristoyl carnitine; no gross
      disruption of the bilayer was observed. We hypothesize that the effects of high
      levels of long-chain AC (as found in ischemia or in certain diseases) on cell
      membranes result from molecular effects on membrane functions rather than from
      gross disruption of the lipid bilayer.

PMID- 12235175
TI  - Thermal behavior of liposomes containing PCs with long and very long chain PUFAs
      isolated from retinal rod outer segment membranes.
AB  - About one-fourth the phosphatidylcholines (PC) from retina photoreceptor rod
      outer segment (ROS) membranes contain docosahexaenoic acid (22:6n-3) at sn-2 and
      a very long chain polyunsaturated fatty acid (VLCPUFA) (C24 to C36) at the sn-1
      position of the glycerol backbone. In order to study the thermotropic behavior of
      these PCs, subfractions and molecular species of PC (16:0/22:6, 18:0/22:6,
      22:6/22:6, 32:5/22:6, 32:6/22:6, 34:5/22:6), were isolated from bovine ROS, and
      liposomes containing different proportions of these PCs and dimyristoyl-PC (DMPC)
      or dipalmitoyl PC (DPPC) were compared using the fluorescence probes Laurdan and
      1,6-diphenyl-1,3,5-hexatriene (DPH). With both probes, the 22:6n-3 containing PCs
      from ROS, in all proportions tested, decreased the transition temperature (Tt) of
      both DMPC and DPPC. Below the transition temperature, coexistence of phases was
      evidenced in all cases. Liposomes formed with 100% of any of these PCs did not
      show phase transitions in the temperature range studied (8 degrees C to 50
      degrees C). At physiological temperatures, as it is likely to be the case in ROS
      membranes, all of these PC species were in the liquid-crystalline state. With
      Laurdan, all dipolyunsaturated PCs seemed to behave similarly: despite the large
      number of double bonds per molecule, all of them decreased the Tt of DPPC less
      than did the hexaenoic PCs. With DPH, an ample difference was detected between
      the dipolyunsaturates, 22:6/22:6-PC and VLCPUFA/22:6-PCs, and between the latter
      and hexaenoic PCs throughout the temperature range studied. This difference is
      consistent with the interpretation that the largest "disorder" produced by PCs
      containing a VLCPUFA like 32:6n-3 at the sn-1 position occurs toward the center
      of the membrane.

PMID- 12235176
TI  - ApoC-III gene polymorphisms and risk of coronary artery disease.
AB  - Several polymorphisms in the apolipoprotein C-III (apoC-III) gene have been
      associated with hypertriglyceridemia, but the link with coronary artery disease
      risk is still controversial. In particular, apoC-III promoter sequence variants
      in the insulin responsive element (IRE), constitutively resistant to
      downregulation by insulin, have never been investigated in this connection. We
      studied a total of 800 patients, 549 of whom had angiographically documented
      coronary atherosclerosis, whereas 251 had normal coronary arteriograms. We
      measured plasma lipids, insulin, apoA-I, apoB, and apoC-III and assessed three
      polymorphisms in the apoC-III gene, namely, T-455C in the IRE promoter region,
      C1100T in exon 3, and Sst1 polymorphic site (S1/S2) in the 3' untranslated
      region. Each variant influenced triglyceride levels, but only the T-455C (in
      homozygosity) and S2 alleles influenced apoC-III levels. In coronary artery
      disease (CAD) patients, 18.6% were homozygous for the -455C variant compared with
      only 9.2% in CAD-free group (P < 0.001). In logistic regression models,
      homozygosity for -455C variant was associated with a significantly increased risk
      of CAD (OR = 2.5 and 2.18 for unadjusted and adjusted models, respectively)
      suggesting that it represents an independent genetic susceptibility factor for
      CAD.

PMID- 12235177
TI  - The HIV protease inhibitor ritonavir increases lipoprotein production and has no
      effect on lipoprotein clearance in mice.
AB  - This study examined the effect of human immunodeficiency virus (HIV) protease
      inhibitor therapy on lipoprotein production and catabolism in vivo. The HIV
      protease inhibitor ritonavir was given to C57BL/6 mice fed either a basal low-fat
      diet or a Western type high-fat diet. Fasted mice were injected with Triton
      WR1339 followed by hourly blood collection to monitor lipoprotein production.
      Results showed that ritonavir increased VLDL triglyceride production by 30% over
      a 4 h period when mice were fed the low-fat basal diet. The ritonavir effect was
      more pronounced under high-fat feeding conditions, with a 2-fold increase in VLDL
      triglyceride production rate. Ritonavir did not alter hepatic expression levels
      of diacylglycerol acyltransferase or microsomal triglyceride transfer protein,
      but increased hepatic apolipoprotein B (apoB) secretion rates under both low- and
      high-fat dietary conditions. In contrast to its effect on lipoprotein production,
      ritonavir did not alter triglyceride-rich lipoprotein clearance from circulation
      under either dietary condition. Taken together, these results indicate that the
      hyperlipidemic effect of HIV protease inhibitors is a direct result of increased
      hepatic lipoprotein production. The mechanism appears to be related to their role
      in preventing proteasome-mediated degradation of apoB and activated sterol
      regulatory element binding proteins in the liver.

PMID- 12235179
TI  - Inheritance of cholesterol metabolism of probands with high or low cholesterol
      absorption.
AB  - Heredity of cholesterol absorption and synthesis was studied in siblings of
      hypercholesterolemic probands with low and high serum cholestanol to cholesterol
      ratio (assumed to indicate low and high absorption of cholesterol, respectively).
      Cholesterol synthesis was assayed with sterol balance technique and measuring
      serum cholesterol precursor to cholesterol ratios (synthesis markers of
      cholesterol), and cholesterol absorption with measuring dietary cholesterol
      absorption percentage and serum plant sterol and cholestanol to cholesterol
      ratios (absorption markers of cholesterol). In the siblings of the low absorption
      families, cholesterol absorption percentage and ratios of absorption markers were
      significantly lower, and cholesterol and bile acid synthesis, cholesterol
      turnover, fecal steroids and ratios of synthesis markers significantly higher
      than in the siblings of the high absorption families. The ratios of absorption
      and synthesis markers were inversely interrelated, and they were correlated with
      cholesterol absorption and synthesis in the siblings. In addition, low absorption
      was associated with high body mass index, low HDL cholesterol, and serum sex
      hormone binding globulin levels, suggesting that low absorption was associated
      with metabolic syndrome. Intrafamily correlations were significant for serum
      synthesis markers, cholestanol, triglycerides, and blood glucose level. In
      conclusion, cholesterol absorption efficiency and synthesis are partly inherited
      phenomena, and they can be predicted by the ratios of non-cholesterol sterols to
      cholesterol in serum.

PMID- 12235178
TI  - Effect of atorvastatin on plasma apoE metabolism in patients with combined
      hyperlipidemia.
AB  - Atorvastatin, a synthetic HMG-CoA reductase inhibitor used for the treatment of
      hyperlipidemia and the prevention of coronary artery disease, significantly
      lowers plasma cholesterol and low-density lipoprotein cholesterol (LDL-C) levels.
      It also reduces total plasma triglyceride and apoE concentrations. In view of the
      direct involvement of apoE in the pathogenesis of atherosclerosis, we have
      investigated the effect of atorvastatin treatment (40 mg/day) on in vivo rates of
      plasma apoE production and catabolism in six patients with combined
      hyperlipidemia using a primed constant infusion of deuterated leucine.
      Atorvastatin treatment resulted in a significant decrease (i.e., 30-37%) in
      levels of total triglyceride, cholesterol, LDL-C, and apoB in all six patients.
      Total plasma apoE concentration was reduced from 7.4 +/- 0.9 to 4.3 +/- 0.2 mg/dl
      (-38 +/- 8%, P < 0.05), predominantly due to a decrease in VLDL apoE (3.4 +/- 0.8
      vs. 1.7 +/- 0.2 mg/dl; -42 +/- 11%) and IDL/LDL apoE (1.9 +/- 0.3 vs. 0.8 +/- 0.1
      mg/dl; -57 +/- 6%). Total plasma lipoprotein apoE transport (i.e., production)
      was significantly reduced from 4.67 +/- 0.39 to 3.04 +/- 0.51 mg/kg/day (-34 +/-
      10%, P < 0.05) and VLDL apoE transport was reduced from 3.82 +/- 0.67 to 2.26 +/-
      0.42 mg/kg/day (-36 +/- 10%, P = 0.057). Plasma and VLDL apoE residence times and
      HDL apoE kinetic parameters were not significantly affected by drug treatment.
      Percentage decreases in VLDL apoE concentration and VLDL apoE production were
      significantly correlated with drug-induced reductions in VLDL triglyceride
      concentration (r = 0.99, P < 0.001; r = 0.88, P < 0.05, respectively, n = 6). Our
      results demonstrate that atorvastatin causes a pronounced decrease in total
      plasma and VLDL apoE concentrations and a significant decrease in plasma and VLDL
      apoE rates of production in patients with combined hyperlipidemia.

PMID- 12235180
TI  - Identification of Egr1 as the oncostatin M-induced transcription activator that
      binds to sterol-independent regulatory element of human LDL receptor promoter.
AB  - Previously, we identified the low density lipoprotein receptor (LDLR) promoter
      region -17 to -1 as a novel sterol-independent regulatory element (SIRE) that
      mediates the stimulating effect of oncostatin M (OM). The goal of this study was
      to identify the OM-induced transcription activator that binds to the SIRE
      sequence. By conducting a electrophoretic mobility shift assay (EMSA) followed by
      UV crosslinking and SDS-PAGE, we show that a protein with a molecular mass of 85
      kDa was present in the OM-induced SIRE DNA-protein complex. Western blotting and
      supershift assays reveal that the 85 kDa factor is early growth response gene 1
      (Egr1). The interaction of Egr1 with the SIRE sequence was further confirmed in
      vivo by chromatin immunoprecipitation assays. The functional role of Egr1 in LDLR
      transcription was assessed by cotransfection of an Egr1 expression vector with an
      LDLR promoter reporter construct. We show that overexpression of Egr1
      significantly increases LDLR promoter activity when cotransfected with
      CCAAT/enhancer binding protein beta (c/EBPbeta) or with cAMP-responsive element
      binding protein (CREB) expression vectors. Our studies clearly demonstrate that
      Egr1 is the OM-induced transcription factor that binds to the SIRE sequence of
      the LDLR promoter and also suggest that Egr1 may have a functional role in OM
      induced upregulation of LDLR transcription through interaction with other SIRE
      binding proteins such as c/EBPbeta or CREB.

PMID- 12235181
TI  - Omega-carboxyl variants of 7-ketocholesteryl esters are ligands for beta(2)
      glycoprotein I and mediate antibody-dependent uptake of oxidized LDL by
      macrophages.
AB  - beta(2)-Glycoprotein I (beta(2)-GPI) is a major antigen for anticardiolipin
      antibodies (aCL, Abs) present in patients with antiphospholipid syndrome. We
      recently reported that beta(2)-GPI specifically binds to oxidized LDL (oxLDL) and
      that the beta(2)-GPI's major ligand, oxLig-1 is 7-ketocholesteryl-9
      carboxynonanoate (Kobayashi, K., E. Matsuura, Q. P. Liu, J. Furukawa, K. Kaihara,
      J. Inagaki, T. Atsumi, N. Sakairi, T. Yasuda, D. R. Voelker, and T. Koike. 2001.
      A specific ligand for beta(2)-glycoprotein I mediates autoantibody-dependent
      uptake of oxidized low density lipoprotein by macrophages. J. Lipid Res. 42: 697
      709). In the present study, we demonstrate that omega-carboxylated 7
      ketocholesteryl esters are critical for beta(2)-GPI binding. A positive ion mass
      spectrum of a novel ligand, designated oxLig-2, showed fragmented ions at m/z 383
      and 441 in the presence of acetone, which share features of oxLig-1 and 7
      ketocholesterol. In the negative ion mode, ions at m/z 627, 625, and 243 were
      observed. oxLig-2 was most likely 7-ketocholesteryl-12-carboxy (keto)
      dodecanoate. These ligands were recognized by beta(2)-GPI. Liposome binding to
      macrophages was significantly increased depending on the ligand's concentration,
      in the presence of beta(2)-GPI and an anti-beta(2)-GPI Ab. Synthesized variant, 7
      ketocholesteryl-13-carboxytridecanoate (13-COOH-7KC), also showed a significant
      interaction with beta(2)-GPI and a similar binding profile with macrophages.
      Methylation of the carboxyl function diminished all of the specific ligand
      interactions with beta(2)-GPI. Thus, omega-carboxyl variants of 7-ketocholesteryl
      esters can mediate anti-beta(2)-GPI Ab-dependent uptake of oxLDL by macrophages,
      and autoimmune atherogenesis linked to beta(2)-GPI interaction with oxLDL.

PMID- 12235182
TI  - The N-linked oligosaccharides at the amino terminus of human apoB are important
      for the assembly and secretion of VLDL.
AB  - We determined the role of N-linked glycosylation of apolipoprotein B (apoB) in
      the assembly and secretion of lipoproteins using transfected rat hepatoma McA
      RH7777 cells expressing human apoB-17, apoB-37, and apoB-50, three apoB variants
      with different ability to recruit neutral lipids. Substituting Asn residue with
      Gln at the single glycosylation site within apoB-17 (N(158)) decreased its
      secretion efficiency to a level equivalent to that of wild-type apoB-17 treated
      with tunicamycin, but had little effect on its synthesis or intracellular
      distribution. When selective N-to-Q substitution was introduced at one or more of
      the five N-linked glycosylation sites within apoB-37 (N(158), N(956), N(1341),
      N(1350), and N(1496)), secretion efficiency of apoB-37 from transiently
      transfected cells was variably affected. When all five N-linked glycosylation
      sites were mutated within apoB-37, the secretion efficiency and association with
      lipoproteins were decreased by >50% as compared with wild-type apoB-37.
      Similarly, mutant apoB-50 with all of its N-linked glycosylation sites
      mutagenized showed decreased secretion efficiency and decreased lipoprotein
      association in both d < 1.02 and d > 1.02 g/ml fractions. The inability of mutant
      apoB-37 and apoB-50 to associate with very low-density lipoproteins was
      attributable to impaired assembly and was not due to the limitation of lipid
      availability. The decreased secretion of mutant apoB-17 and apoB-37 was not
      accompanied by accumulation within the cells, suggesting that the proportion of
      mutant apoB not secreted was rapidly degraded. However unlike apoB-17 or apoB-37,
      accumulation of mutant apoB-50 was observed within the endoplasmic reticulum and
      Golgi compartments. These data imply that the N-glycans at the amino terminus of
      apoB play an important role in the assembly and secretion of lipoproteins
      containing the carboxyl terminally truncated apoB.

PMID- 12235183
TI  - Fatty acids differentially regulate hepatic cholesteryl ester formation and
      incorporation into lipoproteins in the liver of the mouse.
AB  - These experiments tested the hypothesis that fatty acids (FAs) that drive
      cholesterol esterification also enhance sterol secretion and were undertaken
      using a mouse model where lipoprotein-cholesterol output by the liver could be
      assessed in vivo. The turnover of sterol in the animals was kept constant (
      approximately 160 mg/d per kg) while the liver was enriched with the single FAs
      8:0, 14:0, 18:1, or 18:2. Under these conditions, the steady-state concentration
      of cholesteryl ester in the liver varied 6-fold, from 1.2 to 7.9 mg/g, and the
      expansion of this pool was directly related to the specific FA enriching the
      liver (FA 18:1>18:2>8:0> 14:0). Secretion of lipoprotein-cholesterol varied 5
      fold and was a linear function of the concentration of cholesteryl ester in the
      liver. These studies demonstrate that unsaturated FAs drive the esterification
      reaction and enhance lipoprotein cholesterol secretion by the liver under
      conditions where cholesterol balance across this organ is constant. Thus,
      individual FAs interact with cholesterol to profoundly regulate both the output
      and uptake of sterol by the liver, and these effects are articulated through the
      esterification reaction.

PMID- 12235184
TI  - ApoB-48 and apoB-100 differentially influence the expression of type-III
      hyperlipoproteinemia in APOE*2 mice.
AB  - Apolipoprotein E (apoE) is essential for the clearance of plasma chylomicron and
      VLDL remnants. The human APOE locus is polymorphic and 5-10% of APOE*2
      homozygotes exhibit type-III hyperlipoproteinemia (THL), while the remaining
      homozygotes have less than normal plasma cholesterol. In contrast, mice
      expressing APOE*2 in place of the mouse Apoe (Apoe(2/2) mice) are markedly
      hyperlipoproteinemic, suggesting a species difference in lipid metabolism (e.g.,
      editing of apolipoprotein B) enhances THL development. Since apoB-100 has an LDLR
      binding site absent in apoB-48, we hypothesized that the Apoe(2/2) THL phenotype
      would improve if all Apoe(2/2) VLDL contained apoB-100. To test this, we crossed
      Apoe(2/2) mice with mice lacking the editing enzyme for apoB (Apobec(-/-)).
      Consistent with an increase in remnant clearance, Apoe(2/2). Apobec(-/-) mice
      have a significant reduction in IDL/LDL cholesterol (IDL/LDL-C) compared with
      Apoe(2/2) mice. However, Apoe(2/2).Apobec(-/-) mice have twice as much VLDL
      triglyceride as Apoe(2/2) mice. In vitro tests show the apoB-100-containing VLDL
      are poorer substrates for lipoprotein lipase than apoB-48-containing VLDL. Thus,
      despite a lowering in IDL/LDL-C, substituting apoB-48 lipoproteins with apoB-100
      lipoproteins did not improve the THL phenotype in the Apoe(2/2).Apobec(-/-) mice,
      because apoB-48 and apoB-100 differentially influence the catabolism of
      lipoproteins.

PMID- 12235185
TI  - Brain astrocyte synthesis of docosahexaenoic acid from n-3 fatty acids is limited
      at the elongation of docosapentaenoic acid.
AB  - The phospholipids, particularly phosphatidylethanolamine, of brain gray matter
      are enriched with docosahexaenoic acid (22:6n-3). The importance of uptake of
      preformed 22:6n-3 from plasma compared with synthesis from the alpha-linolenic
      acid (18:3n-3) precursor in brain is not known. Deficiency of 18:3n-3 results in
      a compensatory increase in the n-6 docosapentaenoic acid (22:5n-6) in brain,
      which could be formed from the precursor linoleic acid (18:2n-6) in liver or
      brain. We studied n-3 and n-6 fatty acid incorporation in brain astrocytes
      cultured in chemically defined medium using delipidated serum supplemented with
      specific fatty acids. High performance liquid chromatography with evaporative
      light scattering detection and gas liquid chromatography were used to separate
      and quantify cell and media lipids and fatty acids. Although astrocytes are able
      to form 22:6n-3, incubation with 18:3n-3 or eicosapentaenoic acid (20:5n-3)
      resulted in a time and concentration dependent accumulation of 22:5n-3 and
      decrease in 22:6n-3 g/g cell fatty acids. Astrocytes cultured with 18:2n-6 failed
      to accumulate 22:5n-6. Astrocytes secreted cholesterol esters (CE) and
      phosphatidylethanolamine containing saturated and monounsaturated fatty acids,
      and arachidonic acid (20:4n-6) and 22:6n-3. These studies suggest conversion of
      22:5n-3 limits 22:6n-3 synthesis, and show astrocytes release fatty acids in CE.

PMID- 12235186
TI  - Optimizing DHA levels in piglets by lowering the linoleic acid to alpha-linolenic
      acid ratio.
AB  - We examined the effect of altering the linoleic acid (LA, 18:2n-6) to alpha
      linolenic acid (ALA, 18:3n-3) ratio in the dietary fats of 3 day old piglets fed
      formula for 3 weeks. The LA-ALA ratios of the experimental formulas were 0.5:1,
      1:1, 2:1, 4:1, and 10:1. The level of LA was held constant at 13% of total fats
      while the level of ALA varied from 1.3% (10:1 group) to 26.8% (0.5:1 group).
      Incorporation of the n-3 long chain PUFA EPA and 22:5n-3 into erythrocytes,
      plasma, liver, and brain tissues was linearly related to dietary ALA. Conversely,
      incorporation of DHA into all tissues was related to dietary ALA in a curvilinear
      manner, with the maximum incorporation of DHA appearing to be between the LA-ALA
      ratios of 4:1 and 2:1. Feeding LA-ALA ratios of 10:1 and 0.5:1 resulted in lower
      and similar proportions of DHA in tissues despite the very different levels of
      dietary ALA (1.3 vs. 26.8% of total fats, respectively). These results are
      relevant to term infant studies in that they confirm our earlier findings of the
      positive effect on DHA status by lowering the LA-ALA ratio from 10:1 to 3:1 or
      4:1, and they predict that ratios of LA-ALA below 4:1 would have little further
      beneficial effect on DHA status.

PMID- 12235188
TI  - Distinct ontogenic patterns of overt and latent DGAT activities of rat liver
      microsomes.
AB  - We have studied the ontogeny of the two functional diacylglycerol acyltransferase
      (DGAT) activities (overt and latent) during postnatal development in rat liver.
      We find that the ontogenic patterns of the two are highly distinct. Overt DGAT
      shows a transient rise in activity up to day 4 postnatally, after which it
      declines until weaning; thereafter, it increases steadily to reach high adult
      values that may contribute to the high rates of turnover of cytosolic
      triacylglycerol (TAG). By contrast, latent DGAT activity increases continuously
      during the suckling period but falls sharply upon weaning onto chow but not onto
      a high-fat diet. Rates of TAG secretion by hepatocytes are higher than in the
      adult during the first 7 days after birth, and are largely dependent on the
      mobilization of the abundant intrahepatocyte TAG as a source of acyl moieties.
      When the hepatic steatosis is cleared (after day 7) the TAG secretion rate
      declines by 80% to reach adult values. Quantification of the content of mRNA for
      the DGAT1 and DGAT2 genes does not show correlation with either of the DGAT
      activities. We conclude that post-translational modification may play an
      important role in the overt and latent distribution of DGAT activity in the liver
      microsomal membrane.

PMID- 12235187
TI  - Inhibition of hepatocyte apoB secretion by naringenin: enhanced rapid
      intracellular degradation independent of reduced microsomal cholesteryl esters.
AB  - The grapefruit flavonoid, naringenin, is hypocholesterolemic in vivo, and
      inhibits basal apolipoprotein B (apoB) secretion and the expression and
      activities of both ACAT and microsomal triglyceride transfer protein (MTP) in
      human hepatoma cells (HepG2). In this report, we examined the effects of
      naringenin on apoB kinetics in oleate-stimulated HepG2 cells and determined the
      contribution of microsomal lumen cholesteryl ester (CE) availability to apoB
      secretion. Pulse-chase studies of apoB secretion and intracellular degradation
      were analyzed by multicompartmental modeling. The model for apoB metabolism in
      HepG2 cells includes an intracellular compartment from which apoB can be either
      secreted or degraded by both rapid and slow pathways. In the presence of 0.1 mM
      oleic acid, naringenin (200 micro M) reduced the secretion of newly synthesized
      apoB by 52%, due to a 56% reduction in the rate constant for secretion.
      Intracellular degradation was significantly increased due to a selective increase
      in rapid degradation, while slow degradation was unaffected. Incubation with
      either N-acetyl-leucinyl-leucinyl-norleucinal (ALLN) or lactacystin showed that
      degradation via the rapid pathway was largely proteasomal. Although these changes
      in apoB metabolism were accompanied by significant reductions in CE synthesis and
      mass, subcellular fractionation experiments comparing naringenin to specific ACAT
      and HMG-CoA reductase inhibitors revealed that reduced accumulation of newly
      synthesized CE in the microsomal lumen is not consistently associated with
      reduced apoB secretion. However, naringenin, unlike the ACAT and HMG-CoA
      reductase inhibitors, significantly reduced lumenal TG accumulation. We conclude
      that naringenin inhibits apoB secretion in oleate-stimulated HepG2 cells and
      selectively increases intracellular degradation via a largely proteasomal, rapid
      kinetic pathway. Although naringenin inhibits ACAT, CE availability in the
      endoplasmic reticulum (ER) lumen does not appear to regulate apoB secretion in
      HepG2 cells. Rather, inhibition of TG accumulation in the ER lumen via inhibition
      of MTP is the primary mechanism blocking apoB secretion.

PMID- 12235189
TI  - The simultaneous quantification of cytochrome P450 dependent linoleate and
      arachidonate metabolites in urine by HPLC-MS/MS.
AB  - A method for the simultaneous quantification of urinary linoleic and arachidonic
      acid derived epoxides and diols, as well as the arachidonate omega hydroxylated
      product has been developed. The method employs negative mode electrospray
      ionization and HPLC with tandem mass spectroscopy for quantification. Odd chain
      length saturated epoxy and dihydroxy fatty acids are used as analytical
      surrogates resulting in linear calibrations (r (2) > or = 0.9995). Standard
      addition analyses showed that matrix effects do not prevent these surrogates from
      yielding reliable quantitative results. Using 4 ml urine aliquots at a final
      extract volume of 100 micro l and injecting 10 micro l, method detection limits
      and limits of quantification were < or =0.5 and 1.5 nM, respectively. The
      sensitivity for dihydroxy lipids was from 3- to 10-fold greater than the
      corresponding epoxy fatty acid. Shot to shot run times of 31 min were achieved.
      Rodent and human urine analyses indicated the method sensitivity is sufficient
      for general research applications. In addition, diurnal fluctuations in linoleate
      and arachidonate derived metabolites were observed in human subjects.

PMID- 12235190
TI  - International workshop on cellular and molecular aspects of omega-3 fatty acids
      and cancer.

PMID- 12235191
TI  - Protein turnover, amino acid profile and amino acid flux in juvenile shrimp
      Litopenaeus vannamei: effects of dietary protein source.
AB  - The effect of dietary protein on protein synthesis and growth of juvenile shrimps
      Litopenaeus vannamei was investigated using three different diets with equivalent
      protein content. Protein synthesis was investigated by a flooding dose of
      tritiated phenylalanine. Survival, specific growth and protein synthesis rates
      were higher, and protein degradation was lower, in shrimps fed a
      fish/squid/shrimp meal diet, or a 50% laboratory diet/50% soybean meal variant
      diet, than in those fed a casein-based diet. The efficiency of retention of
      synthesized protein as growth was 94% for shrimps fed the fish meal diet,
      suggesting a very low protein turnover rate; by contrast, the retention of
      synthesized protein was only 80% for shrimps fed the casein diet. The amino acid
      profile of the casein diet was poorly correlated with that of the shrimps. 4 h
      after a single meal the protein synthesis rates increased following an increase
      in RNA activity. A model was developed for amino acid flux, suggesting that high
      growth rates involve a reduction in the turnover of proteins, while amino acid
      loss appears to be high.

PMID- 12235192
TI  - Enhanced haemolymph circulation by insect ventral nerve cord: hormonal control by
      Pseudaletia unipuncta allatotropin and serotonin.
AB  - The ventral diaphragm (VD) in many insects is a muscular membrane that
      essentially partitions a perineural sinus from the rest of the abdomen. In the
      true armyworm moth Pseudaletia unipuncta (Lepidoptera: Noctuidae) we describe how
      the VD is characterized by a series of aliform muscles inserted into a tissue
      matrix that is fused to the dorsal surface of the ventral nerve cord (VNC)
      itself. Because of this arrangement, the abdominal VNC can attain high rates of
      lateral oscillation, and is capable of directing haemolymph flow. We have
      previously demonstrated Manduca sexta allatotropin (Manse-AT)-like
      immunoreactivity throughout the central nervous system (CNS) in P. unipuncta, and
      that both Manse-AT and serotonin (5-HT) are dose-dependent stimulators of the
      dorsal vessel. Here we describe both Manse-AT- and 5-HT-like immunoreactivity
      associated with the VD. Furthermore, both Manse-AT and 5-HT are dose-dependent
      stimulators of the rates of VNC oscillation, and together are capable of
      maintaining highly elevated rates of VNC oscillation for extended periods of
      time. These data indicate that both the dorsal vessel and the VD/VNC are
      similarly modulated by both Manse-AT and 5-HT, and that VNC oscillations play a
      more active role in overall haemolymph circulation than previously recognized.

PMID- 12235193
TI  - The superfast extraocular myosin (MYH13) is localized to the innervation zone in
      both the global and orbital layers of rabbit extraocular muscle.
AB  - Extraocular muscles (EOMs) are the most molecularly heterogeneous and
      physiologically diverse mammalian striated muscles. They express the entire array
      of striated muscle myosins, including a specialized myosin heavy chain MYH13,
      which is restricted to extraocular and laryngeal muscles. EOMs also exhibit a
      breadth of contractile activity, from superfast saccades to slow tracking and
      convergence movements. These movements are accomplished by the action of six
      ultrastructurally defined fiber types that differ from the type IIa, IIb, IIx and
      I fibers found in other skeletal muscles. Attempts to associate different eye
      movements with either the expression of different myosins or the activity of
      particular EOM fiber types are complicated by the molecular heterogeneity of
      several of the fiber types, and by electromyography studies showing that the
      majority of extraocular motor units participate in both fast and slow eye
      movements. To better understand the role of MYH13 in ocular motility, we
      generated MYH13-sequence-specific antibodies and used SDS-PAGE to quantify the
      regional distribution of myosin in EOM and to characterize its heterogeneity in
      single fibers. These studies demonstrate that MYH13 is preferentially expressed
      in the majority of orbital and global fibers in the central innervation zone of
      rabbit EOM. Many individual fibers express MYH13 with the fast IIb myosin and
      varying amounts of IIx myosin. The differential localization of MYH13, coupled
      with specialization of the sarcoplasmic reticulum and thin filament systems,
      probably explains how activation of the endplate band region enables the majority
      of EOM fibers to contribute to superfast contractions.

PMID- 12235194
TI  - Regulation of early embryonic behavior by nitric oxide in the pond snail Helisoma
      trivolvis.
AB  - Helisoma trivolvis embryos display a cilia-driven rotational behavior that is
      regulated by a pair of serotonergic neurons named ENC1s. As these cilio
      excitatory motor neurons contain an apical dendrite ending in a chemosensory
      dendritic knob at the embryonic surface, they probably function as sensorimotor
      neurons. Given that nitric oxide (NO) is often associated with sensory neurons in
      invertebrates, and has also been implicated in the control of ciliary activity,
      we examined the expression of NO synthase (NOS) activity and possible function of
      NO in regulating the rotational behavior in H. trivolvis embryos. NADPH
      diaphorase histochemistry on stage E25-E30 embryos revealed NOS expression in the
      protonephridia, buccal mass, dorsolateral ciliary cells and the sensory dendritic
      knobs of ENC1. At stages E35-40, the pedal ciliary cells and ENC1's soma, apical
      dendrite and proximal descending axon were also stained. In stage E25 embryos,
      optimal doses of the NO donors SNAP and SNP increased the rate of embryonic
      rotation by twofold, in contrast to the fourfold increase caused by 100 micro mol
      l(-1) serotonin. The NOS inhibitors L-NAME (10 mmol l(-1)) and 7-NI (100 micro
      mol l(-1)) decreased the rotation rate by approximately 50%, whereas co-addition
      of L-NAME and SNAP caused a twofold increase. In an analysis of the surge and
      inter-surge subcomponents of the rotational behavior, the NO donors increased the
      inter-surge rotation rate and the surge amplitude. In contrast, the NO inhibitors
      decreased the inter-surge rotation rate and the frequency of surges. These data
      suggest that the embryonic rotational behavior depends in part on the
      constitutive excitatory actions of NO on ENC1 and ciliary cells.

PMID- 12235195
TI  - Vibrometric studies of the middle ear of the bullfrog Rana catesbeiana I. The
      extrastapes.
AB  - Laser vibrometry was used to measure the vibration velocity at different points
      on the ossicular apparatus of the bullfrog Rana catesbeiana in response to free
      field sound. The ascending process of the extrastapes, neglected in most accounts
      of frog middle ear mechanics, supports a rocking motion of the extrastapes and is
      critical to the normal function of the ossicular apparatus. The articulation
      between extrastapes and the bony stapes shaft acts as a hinge, although movement
      at this hinge is usually small. The ratio of tympanic membrane to footplate
      vibration velocity is significantly greater in male frogs than in female frogs.
      Differences in this ratio between male and female frogs are probably mainly due
      to flexion between the extrastapes and stapes rather than to differences in the
      coupling between tympanic membrane and extrastapes. It is argued that flexibility
      in the ossicular system represents a protective mechanism in frogs, and
      functional analogies are drawn between the stapes/extrastapes system of frogs and
      the tri-ossicular system of mammals.

PMID- 12235196
TI  - Vibrometric studies of the middle ear of the bullfrog Rana catesbeiana II. The
      operculum.
AB  - The operculum and stapes footplate, the two moveable elements within the oval
      window of the frog, have been thought to function independently. In this study,
      laser interferometry was used to record the vibrations of both structures in
      response to free-field airborne sound. Contrary to expectation, the operculum
      appears to be coupled to the footplate. Coupling is achieved both by means of
      ligaments and by a cartilaginous flange of the footplate that underlies the
      operculum. The stapes footplate rotates about an axis located ventrolaterally,
      but the axis for the operculum is dorsomedial. As a result of this unusual
      morphology, the opercularis muscle, which connects the operculum and shoulder
      girdle, can potentially affect the movements of both the operculum and footplate.
      The proposed roles of the opercularis system in seismic signal detection and
      extratympanic sound transmission are critically reviewed in the light of this new
      evidence. An alternative or additional role for the opercularis system is
      proposed, involving the protection of the inner ear from high-amplitude
      displacements of the stapes footplate during breathing and vocalisation.

PMID- 12235197
TI  - A kinematic model of swallowing in Aplysia californica based on
      radula/odontophore kinematics and in vivo magnetic resonance images.
AB  - A kinematic model of the buccal mass of Aplysia californica during swallowing has
      been developed that incorporates the kinematics of the odontophore, the muscular
      structure that underlies the pincer-like grasping structure, the radula. The
      model is based on real-time magnetic resonance images (MRIs) of the mid-sagittal
      cross section of the buccal mass during swallowing. Using kinematic relationships
      derived from isolated odontophores induced to perform feeding-like movements, the
      model generates predictions about movement of the buccal mass in the medio
      lateral dimension during the feeding cycle that are well-matched to corresponding
      coronal MRIs of the buccal mass during swallowing. The model successfully
      reproduces changes in the lengths of the intrinsic (I) buccal muscles I2 and I3
      measured experimentally. The model predicts changes in the length of the radular
      opener muscle I7 throughout the swallowing cycle, generates hypotheses about the
      muscular basis of radular opening prior to the onset of forward rotation during
      swallowing and suggests possible context-dependent functions for the I7 muscle,
      the radular stalk and the I5 (ARC) muscle during radular opening and closing.

PMID- 12235198
TI  - Individual variation in metabolic traits of wild nine-banded armadillos (Dasypus
      novemcinctus), and the aerobic capacity model for the evolution of endothermy.
AB  - A fundamental assumption of the aerobic capacity model for the evolution of
      endothermy is that basal (BMR) and peak (PMR) metabolic rates are functionally
      linked at the intraspecific level. The purpose of this study was to use the nine
      banded armadillo Dasypus novemcinctus as a model to test this assumption.
      Measurements of BMR, PMR, mass and rectal temperature were obtained over two
      summers from wild, adult individuals from a population in Louisiana, USA. BMR and
      PMR were positively correlated (r=0.62), and both were significantly higher (by
      46% for BMR and by 35% for PMR) in 1999 than in 1998. Similar results were
      obtained whether metabolic rates were expressed in whole-animal or mass
      independent units. These results suggest the existence of a functional link
      between BMR and PMR and are therefore consistent with the aerobic capacity model.
      In addition, this study confirmed that, compared with most eutherian mammals, the
      nine-banded armadillo exhibits low and highly variable basal and peak metabolic
      rates (20-60% the predicted values; 23% and 27% coefficients of variation) and
      rectal temperatures (range 32.7-35.3 degrees C). Such metabolic traits are,
      however, consistent with the general pattern previously observed for other
      members of the order Xenarthra and with the hypothesis that low metabolic rates
      in armored mammals evolved as a result of unbalanced selection in which, because
      of low predation risks, selection for a high aerobic capacity was much weaker
      than the opposing selection for energy conservation.

PMID- 12235199
TI  - Effects of age and size in the ears of gekkonomorph lizards: middle-ear
      sensitivity.
AB  - Previous studies of electrophysiological audiograms in gekkonomorph lizards
      revealed greater sensitivity in adults than in juveniles. We investigated whether
      this difference, as far as it is affected by the middle ear, is due to animal age
      or size. The velocity transfer function of the tympanic membrane (TM) was
      examined using laser interferometry in nine samples: adults of three large
      gekkonomorph species, adults of three small species (each related to one of the
      former), and juveniles of the large species, their sizes matching those of the
      small-species adults. Each transfer function exhibited an inverted 'V' or 'U'
      shape, with the velocity of TM motion peaking in the mid-frequency range and
      becoming poorer at lower and higher frequencies. Among samples, maximum TM
      velocity correlated with animal length, perhaps because of a damping change in
      the larger TM. The frequency at maximum velocity negatively correlated with
      measurements of TM area. Presumably, with a larger TM area, the best frequency
      shifted downward because of increased middle-ear mass or decreased stiffness. The
      bandwidth of the transfer function negatively correlated with animal length,
      being broader in smaller animals and sharper in larger animals. This effect can
      be attributed to increased mass, decreased damping, or both. Among the middle-ear
      morphological measurements, the one most closely correlated with body length was
      the length of the extracolumellar anchorage at the TM. Among the physiological
      variables investigated, maximum velocity was negatively correlated with the
      frequency at which it occurred. The dependence of these transfer function
      variables on animal and ear size was similar, regardless of whether the
      comparison was among adults of species of different sizes, or among age classes
      within a species, so that age differences appear to be largely the result of size
      differences.

PMID- 12235200
TI  - The sun compass of the sandhopper Talitrus saltator: the speed of the
      chronometric mechanism depends on the hours of light.
AB  - Experiments on solar orientation were conducted with adult amphipods (Talitrus
      saltator) subjected to a reduction and/or phase shift of the hours of light (L)
      or dark (D) with respect to the natural photoperiod: 15 h:9 h L:D (controls), 15
      h:9 h inverted (i.e. phase-shifted by 12 h and tested with the sun during the
      subjective night), 4 h:20 h, 20 h:4 h inverted. The sandhoppers were released in
      a confined environment, and individual orientation angles were recorded. The
      results confirm the continuous operation, through the entire 24-h period, of a
      chronometric mechanism of compensation for apparent solar motion. They show
      excellent agreement with a recently proposed model of compensation for the sun at
      constant (not differential) speed and they demonstrate a dependence of the speed
      of the chronometric mechanism on the L:D ratio in the 24-h period.

PMID- 12235201
TI  - Thermal acclimation changes DNA-binding activity of heat shock factor 1 (HSF1) in
      the goby Gillichthys mirabilis: implications for plasticity in the heat-shock
      response in natural populations.
AB  - The intracellular build-up of thermally damaged proteins following exposure to
      heat stress results in the synthesis of a family of evolutionarily conserved
      proteins called heat shock proteins (Hsps) that act as molecular chaperones,
      protecting the cell against the aggregation of denatured proteins. The
      transcriptional regulation of heat shock genes by heat shock factor 1 (HSF1) has
      been extensively studied in model systems, but little research has focused on the
      role HSF1 plays in Hsp gene expression in eurythermal organisms from broadly
      fluctuating thermal environments. The threshold temperature for Hsp induction in
      these organisms shifts with the recent thermal history of the individual but the
      mechanism by which this plasticity in Hsp induction temperature is achieved is
      unknown. We examined the effect of thermal acclimation on the heat-activation of
      HSF1 in the eurythermal teleost Gillichthys mirabilis. After a 5-week acclimation
      period (at 13, 21 or 28 degrees C) the temperature of HSF1 activation was
      positively correlated with acclimation temperature. HSF1 activation peaked at 27
      degrees C in fish acclimated to 13 degrees C, at 33 degrees C in the 21 degrees C
      group, and at 36 degrees C in the 28 degrees C group. Concentrations of both HSF1
      and Hsp70 in the 28 degrees C group were significantly higher than in the colder
      acclimated fish. Plasticity in HSF1 activation may be important to the adjustable
      nature of the heat shock response in eurythermal organisms and the environmental
      control of Hsp gene expression.

PMID- 12235202
TI  - Temperature affects the ontogeny of sexually dimorphic cuticular hydrocarbons in
      Drosophila melanogaster.
AB  - Hydrocarbons on the cuticle of mature Drosophila melanogaster flies play a
      crucial role in mate recognition, and protect against dehydration. We measured
      the effect of temperature on mature cuticular hydrocarbons (CHs) by (i) rearing
      two control strains at different temperatures, (ii) shifting the temperature
      after metamorphosis and (iii) inducing a single heat-shock pulse in control and
      heat-sensitive transgenic strains, over a period of 3 days following adult
      eclosion. This study describes the time course of the events involved in the
      production of male- and female-predominant CHs. We also found that 'immature'
      CHs, sexually monomorphic CHs on younger flies, were not affected by these
      treatments.

PMID- 12235203
TI  - Osmoregulation in the terrestrial Christmas Island red crab Gecarcoidea natalis
      (Brachyura: Gecarcinidae): modulation of branchial chloride uptake from the
      urine.
AB  - Crabs generally produce urine iso-osmotic to their haemolymph, but terrestrial
      crabs are able to vary the composition of their final excretory fluid (termed P)
      postrenally, in the branchial chambers. Regulatory aspects of branchial urine
      processing were investigated in the Christmas Island red crab Gecarcoidea natalis
      acclimated to drinking either freshwater (FW crabs) or 70% seawater (SW crabs).
      FW crabs released dilute P (mean [Cl(-)] 8.8 mmol l(-1)). Drinking 70% seawater
      caused the mean [Cl(-)] of the P to rise to 376 mmol l(-1) over 5 days,
      approaching the haemolymph [Cl(-)]. FW crabs with saline-perfused branchial
      chambers absorbed chloride at a high rate (10 mmol kg(-1) h(-1)), and haemolymph
      [Cl(-)] increased at approximately 20 mmol l(-1) h(-1). SW crabs exhibited
      elevated haemolymph osmolalities and ion concentrations and zero branchial
      chloride uptake. FW crabs that were salt-loaded by branchial chamber perfusion
      over several hours downregulated, and eventually ceased, chloride uptake. The
      rate of downregulation, but not the initial chloride flux, was dependent on
      initial haemolymph [Cl(-)]. Intravascular infusion of NaCl caused immediate
      reduction in branchial [Cl(-)] of 80%. Crabs ingested and regurgitated the
      perfusion saline, supporting suggestions that reingestion of urine could conserve
      water and ions. Dopamine upregulated branchial chloride transport in G. natalis.
      This is consistent with the ion-regulatory effects of dopamine in euryhaline
      marine brachyurans but contrasts with its inhibitory effects in the terrestrial
      anomuran Birgus latro. Dopamine increased the rate of urine release in FW crabs.
      Urine composition appears to be unimportant in ionic regulation, except in the
      case of magnesium, levels of which were elevated in the urine of SW crabs.

PMID- 12235204
TI  - Relationship between the membrane potential of the contractile vacuole complex
      and its osmoregulatory activity in Paramecium multimicronucleatum.
AB  - The electric potential of the contractile vacuole (CV) of Paramecium
      multimicronucleatum was measured in situ using microelectrodes, one placed in the
      CV and the other (reference electrode) in the cytosol of a living cell. The CV
      potential in a mechanically compressed cell increased in a stepwise manner to a
      maximal value (approximately 80 mV) early in the fluid-filling phase. This
      stepwise change was caused by the consecutive reattachment to the CV of the
      radial arms, where the electrogenic sites are located. The current generated by a
      single arm was approximately 1.3x10(-10) A. When cells adapted to a hypotonic
      solution were exposed to a hypertonic solution, the rate of fluid segregation,
      R(CVC), in the contractile vacuole complex (CVC) diminished at the same time as
      immunological labelling for V-ATPase disappeared from the radial arms. When the
      cells were re-exposed to the previous hypotonic solution, the CV potential, which
      had presumably dropped to near zero after the cell's exposure to the hypertonic
      solution, gradually returned to its maximum level. This increase in the CV
      potential occurred in parallel with the recovery of immunological labelling for V
      ATPase in the radial arm and the resumption of R(CVC) or fluid segregation.
      Concanamycin B, a potent V-ATPase inhibitor, brought about significant decreases
      in both the CV potential and R(CVC). We confirm that (i) the electrogenic site of
      the radial arm is situated in the decorated spongiome, and (ii) the V-ATPase in
      the decorated spongiome is electrogenic and is necessary for fluid segregation in
      the CVC. The CV potential remained at a constant high level (approximately 80
      mV), whereas R(CVC) varied between cells depending on the osmolarity of the
      adaptation solution. Moreover, the CV potential did not change even though R(CVC)
      increased when cells adapted to one osmolarity were exposed to a lower
      osmolarity, implying that R(CVC) is not directly correlated with the number of
      functional V-ATPase complexes present in the CVC.

PMID- 12235205
TI  - The formation of lymphatic vessels and its importance in the setting of
      malignancy.

PMID- 12235206
TI  - Lymphangiogenic gene therapy with minimal blood vascular side effects.
AB  - Recent work from many laboratories has demonstrated that the vascular endothelial
      growth factor-C/VEGF-D/VEGFR-3 signaling pathway is crucial for
      lymphangiogenesis, and that mutations of the Vegfr3 gene are associated with
      hereditary lymphedema. Furthermore, VEGF-C gene transfer to the skin of mice with
      lymphedema induced a regeneration of the cutaneous lymphatic vessel network.
      However, as is the case with VEGF, high levels of VEGF-C cause blood vessel
      growth and leakiness, resulting in tissue edema. To avoid these blood vascular
      side effects of VEGF-C, we constructed a viral vector for a VEGFR-3-specific
      mutant form of VEGF-C (VEGF-C156S) for lymphedema gene therapy. We demonstrate
      that VEGF-C156S potently induces lymphangiogenesis in transgenic mouse embryos,
      and when applied via viral gene transfer, in normal and lymphedema mice.
      Importantly, adenoviral VEGF-C156S lacked the blood vascular side effects of VEGF
      and VEGF-C adenoviruses. In particular, in the lymphedema mice functional
      cutaneous lymphatic vessels of normal caliber and morphology were detected after
      long-term expression of VEGF-C156S via an adeno associated virus. These results
      have important implications for the development of gene therapy for human
      lymphedema.

PMID- 12235207
TI  - Vaccination with minigenes encoding V(H)-derived major histocompatibility complex
      class I-binding epitopes activates cytotoxic T cells that ablate autoantibody
      producing B cells and inhibit lupus.
AB  - Current treatments for autoantibody-mediated diseases, such as lupus, can cause
      nonspecific immune suppression. In this paper, we used a bioinformatic approach
      to identify major histocompatibility complex class I-binding epitopes in the
      heavy chain variable region of anti-DNA antibodies from lupus-prone (NZB/NZW F1)
      mice. Vaccination of such mice with plasmid DNA vectors encoding these epitopes
      induced CD8(+) T cells that killed anti-DNA antibody-producing B cells, reduced
      serum anti-DNA antibody levels, retarded the development of nephritis, and
      improved survival. Vaccine-mediated induction of anti-V(H) cytotoxic T
      lymphocytes that ablate autoreactive B cells represents a novel approach to treat
      autoantibody-mediated diseases.

PMID- 12235208
TI  - IkappaB kinase signaling is essential for maintenance of mature B cells.
AB  - Nuclear factor (NF)-kappaB proteins play crucial roles in immune responses and
      cellular survival. Activation of NF-kappaB is mediated by the IkappaB kinase
      (IKK) complex, which is composed of two kinases, IKK1 and IKK2, and a regulatory
      subunit termed NF-kappaB essential modulator (NEMO). IKK2- and NEMO-deficient
      mice die at early embryonic stages. We therefore used conditional gene targeting
      to evaluate the role of these proteins in B cells in adult mice. B lineage
      specific disruption of either IKK signaling by deletion of NEMO, or of IKK2
      specific signals by ablation of IKK2 activity leads to the disappearance of
      mature B lymphocytes. We conclude that maintenance of mature B cells depends on
      IKK-mediated activation of NF-kappaB.

PMID- 12235209
TI  - A crucial role for the p110delta subunit of phosphatidylinositol 3-kinase in B
      cell development and activation.
AB  - Mice lacking the p110delta catalytic subunit of phosphatidylinositol 3-kinase
      have reduced numbers of B1 and marginal zone B cells, reduced levels of serum
      immunoglobulins, respond poorly to immunization with type II thymus-independent
      antigen, and are defective in their primary and secondary responses to thymus
      dependent antigen. p110delta(-/-) B cells proliferate poorly in response to B
      cell receptor (BCR) or CD40 signals in vitro, fail to activate protein kinase B,
      and are prone to apoptosis. p110delta function is required for BCR-mediated
      calcium flux, activation of phosphlipaseCgamma2, and Bruton's tyrosine kinase.
      Thus, p110delta plays a critical role in B cell homeostasis and function.

PMID- 12235210
TI  - DeltaNp73, a dominant-negative inhibitor of wild-type p53 and TAp73, is up
      regulated in human tumors.
AB  - p73 has significant homology to p53. However, tumor-associated up-regulation of
      p73 and genetic data from human tumors and p73-deficient mice exclude a classical
      Knudson-type tumor suppressor role. We report that the human TP73 gene generates
      an NH(2) terminally truncated isoform. DeltaNp73 derives from an alternative
      promoter in intron 3 and lacks the transactivation domain of full-length TAp73.
      DeltaNp73 is frequently overexpressed in a variety of human cancers, but not in
      normal tissues. DeltaNp73 acts as a potent transdominant inhibitor of wild-type
      p53 and transactivation-competent TAp73. DeltaNp73 efficiently counteracts
      transactivation function, apoptosis, and growth suppression mediated by wild-type
      p53 and TAp73, and confers drug resistance to wild-type p53 harboring tumor
      cells. Conversely, down-regulation of endogenous DeltaNp73 levels by antisense
      methods alleviates its suppressive action and enhances p53- and TAp73-mediated
      apoptosis. DeltaNp73 is complexed with wild-type p53, as demonstrated by
      coimmunoprecipitation from cultured cells and primary tumors. Thus, DeltaNp73
      mediates a novel inactivation mechanism of p53 and TAp73 via a dominant-negative
      family network. Deregulated expression of DeltaNp73 can bestow oncogenic activity
      upon the TP73 gene by functionally inactivating the suppressor action of p53 and
      TAp73. This trait might be selected for in human cancers.

PMID- 12235211
TI  - Histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, autoantigens in
      myositis, activate chemokine receptors on T lymphocytes and immature dendritic
      cells.
AB  - Autoantibodies to histidyl-tRNA synthetase (HisRS) or to alanyl-, asparaginyl-,
      glycyl-, isoleucyl-, or threonyl-tRNA synthetase occur in approximately 25% of
      patients with polymyositis or dermatomyositis. We tested the ability of several
      aminoacyl-tRNA synthetases to induce leukocyte migration. HisRS induced CD4(+)
      and CD8(+) lymphocytes, interleukin (IL)-2-activated monocytes, and immature
      dendritic cells (iDCs) to migrate, but not neutrophils, mature DCs, or
      unstimulated monocytes. An NH(2)-terminal domain, 1-48 HisRS, was chemotactic for
      lymphocytes and activated monocytes, whereas a deletion mutant, HisRS-M, was
      inactive. HisRS selectively activated CC chemokine receptor (CCR)5-transfected
      HEK-293 cells, inducing migration by interacting with extracellular domain three.
      Furthermore, monoclonal anti-CCR5 blocked HisRS-induced chemotaxis and
      conversely, HisRS blocked anti-CCR5 binding. Asparaginyl-tRNA synthetase induced
      migration of lymphocytes, activated monocytes, iDCs, and CCR3-transfected HEK-293
      cells. Seryl-tRNA synthetase induced migration of CCR3-transfected cells but not
      iDCs. Nonautoantigenic aspartyl-tRNA and lysyl-tRNA synthetases were not
      chemotactic. Thus, autoantigenic aminoacyl-tRNA synthetases, perhaps liberated
      from damaged muscle cells, may perpetuate the development of myositis by
      recruiting mononuclear cells that induce innate and adaptive immune responses.
      Therefore, the selection of a self-molecule as a target for an autoantibody
      response may be a consequence of the proinflammatory properties of the molecule
      itself.

PMID- 12235212
TI  - The proliferative capacity of individual naive CD4(+) T cells is amplified by
      prolonged T cell antigen receptor triggering.
AB  - Strong antigenic encounter by T cells rapidly induces immunological synapse
      formation and surface T cell receptor (TCR) downregulation. Although surface TCR
      expression can remain low for several days, T cells can still sustain antigenic
      signaling. It has been unclear whether prolonged antigenic signaling occurs in
      the absence of surface TCR replenishment, being maintained by a few
      "nondownregulatable" surface TCRs that might reside in a synaptosomal structure.
      Alternatively, the low surface TCR level induced by antigen might represent a
      dynamic state of expression involving continual surface TCR replenishment,
      reengagement by antigen, and ongoing downregulation. To resolve this issue, we
      studied in vivo-generated, dual-specificity primary naive CD4(+) T cells. On
      these cells, antigenic stimulus exclusively downregulated antigen-specific, but
      not antigen-nonspecific, TCRs. In addition to providing a means to track TCR
      engagement, this also allowed us to use the antigen nonspecific TCR to track TCR
      expression in isolation from TCR engagement by antigen. Surface TCR replenishment
      began within the first day of stimulation, and occurred synchronously with
      continuous antigen-specific TCR engagement and downregulation. Furthermore, by
      enhancing CD25 expression, extended signaling through surface-replenishing TCRs
      significantly amplified the number of daughter cells generated by naive CD4(+) T
      cells that had already committed to proliferate. This effect required TCR
      engagement and could not be substituted for by interleukin 2. These data
      demonstrate that TCR triggering and consumption can occur over an extended period
      of time, with a significant impact on the effector responses evoked from naive
      CD4(+) T cells.

PMID- 12235213
TI  - Major histocompatibility complex class I allele-specific cooperative and
      competitive interactions between immune evasion proteins of cytomegalovirus.
AB  - Cytomegaloviruses (CMVs) deploy a set of genes for interference with antigen
      presentation in the major histocompatibility complex (MHC) class I pathway. In
      murine CMV (MCMV), three genes were identified so far: m04/gp34, m06/gp48, and
      m152/gp40. While their function as immunoevasins was originally defined after
      their selective expression, this may not necessarily reflect their biological
      role during infection. The three immunoevasins might act synergistically, but
      they might also compete for their common substrate, the MHC class I complexes. To
      approach this question in a systematic manner, we have generated a complete set
      of mutant viruses with deletions of the three genes in all seven possible
      combinations. Surface expression of a set of MHC class I molecules specified by
      haplotypes H-2(d) (K(d), D(d), and L(d)) and H-2(b) (K(b) and D(b)) was the
      parameter for evaluation of the interference with class I trafficking. The data
      show the following: first, there exists no additional MCMV gene of major
      influence on MHC class I surface expression; second, the strength of the
      inhibitory effect of immunoevasins shows an allele-specific hierarchy; and third,
      the immunoevasins act not only synergistically but can, in certain combinations,
      interact antagonistically. In essence, this work highlights the importance of
      studying the immunosubversive mechanisms of cytomegaloviruses in the context of
      gene expression during the viral replicative cycle in infected cells.

PMID- 12235214
TI  - Constitutive versus activation-dependent cross-presentation of immune complexes
      by CD8(+) and CD8(-) dendritic cells in vivo.
AB  - Murine splenic dendritic cells (DCs) can be divided into two subsets based on
      CD8alpha expression, but the specific role of each subset in stimulation of T
      cells is largely unknown. An important function of DCs is the ability to take up
      exogenous antigens and cross-present them in the context of major
      histocompatibility complex (MHC) class I molecules to CD8(+) T cells. We
      previously demonstrated that, when cell-associated ovalbumin (OVA) is injected
      into mice, only the CD8(+) DC subset cross-presents OVA in the context of MHC
      class I. In contrast to this selectivity with cell-associated antigen, we show
      here that both DC subsets isolated from mice injected with OVA/anti-OVA immune
      complexes (OVA-IC) cross-present OVA to CD8(+) T cells. The use of immunoglobulin
      G Fc receptor (Fc(gamma)R) common gamma-chain-deficient mice revealed that the
      cross-presentation by CD8(-) DCs depended on the expression of gamma-chain
      containing activating FcgammaRs, whereas cross-presentation by CD8(+) DCs was not
      reduced in gamma-chain-deficient mice. These results suggest that although CD8(+)
      DCs constitutively cross-present exogenous antigens in the context of MHC class I
      molecules, CD8(-) DCs only do so after activation, such as via ligation of
      Fc(gamma)Rs. Cross-presentation of immune complexes may play an important role in
      autoimmune diseases and the therapeutic effect of antitumor antibodies.

PMID- 12235215
TI  - Inhibition of type 1 cytokine-mediated inflammation by a soluble CD30 homologue
      encoded by ectromelia (mousepox) virus.
AB  - CD30 is up-regulated in several human diseases and viral infections but its role
      in immune regulation is poorly understood. Here, we report the expression of a
      functional soluble CD30 homologue, viral CD30 (vCD30), encoded by ectromelia
      (mousepox) virus, a poxvirus that causes a severe disease related to human
      smallpox. We show that vCD30 is a 12-kD secreted protein that not only binds
      CD30L with high affinity and prevents its interaction with CD30, but it also
      induces reverse signaling in cells expressing CD30L. vCD30 blocked the generation
      of interferon gamma-producing cells in vitro and was a potent inhibitor of T
      helper cell (Th)1- but not Th2-mediated inflammation in vivo. The finding of a
      CD30 homologue encoded by ectromelia virus suggests a role for CD30 in antiviral
      defense. Characterization of the immunological properties of vCD30 has uncovered
      a role of CD30-CD30L interactions in the generation of inflammatory responses.

PMID- 12235216
TI  - Intracrine cysteinyl leukotriene receptor-mediated signaling of eosinophil
      vesicular transport-mediated interleukin-4 secretion.
AB  - We investigated whether cysteinyl leukotrienes (cysLT) are intracrine signal
      transducers that regulate human eosinophil degranulation mechanisms. Interleukin
      (IL)-16, eotaxin, and RANTES stimulate vesicular transport-mediated release of
      preformed, granule-derived IL-4 and RANTES from eosinophils and the synthesis at
      intracellular lipid bodies of LTC(4), the dominant 5-lipoxygenase-derived
      eicosanoid in eosinophils. 5-Lipoxygenase inhibitors blocked IL-16-, eotaxin-,
      and RANTES-induced IL-4 release; but neither exogenous LTC(4), LTD(4), nor LTE(4)
      elicited IL-4 release. Only after membrane permeabilization enabled cysLTs to
      enter eosinophils did LTC(4) and LTD(4) stimulate IL-4, but not RANTES, release.
      LTC(4)-elicited IL-4 release was pertussis toxin inhibitable, but inhibitors of
      the two known G protein-coupled cysLT receptors (cysLTRs) (CysLT1 and CysLT2) did
      not block LTC(4)-elicited IL-4 release. LTC(4) was 10-fold more potent than
      LTD(4) and at low concentrations (0.3-3 nM) elicited, and at higher
      concentrations (>3 nM) inhibited, IL-4 release from permeabilized eosinophils.
      Likewise with intact eosinophils, LTC(4) export inhibitors, which increased
      intracellular LTC(4), inhibited eotaxin-elicited IL-4 release. Thus, LTC(4) acts,
      via an intracellular cysLTR distinct from CysLT1 or CysLT2, as a signal
      transducer to selectively regulate IL-4 release. These results demonstrate that
      LTC(4), well recognized as a paracrine mediator, may also dynamically govern
      inflammatory and immune responses as an intracrine mediator of eosinophil
      cytokine secretion.

PMID- 12235217
TI  - Interleukin 2 signaling is required for CD4(+) regulatory T cell function.
AB  - Mice deficient in interleukin (IL)-2 production or the IL-2 receptor alpha or
      beta chains develop a lethal autoimmune syndrome. CD4(+) regulatory T cells have
      been shown to prevent autoimmune diseases, allograft rejection, and to down
      regulate antibody responses against foreign antigens. To assess the role of IL-2
      in the generation and function of regulatory T cells, we transferred CD4(+) T
      cells from mice genetically deficient in IL-2 or IL-2R(alpha) (CD25) expression.
      A small number of splenic or thymic CD4(+) T cells from IL-2 knockout mice can
      protect mice from spontaneous experimental autoimmune encephalomyelitis (EAE). In
      contrast, splenic or thymic CD4(+) T cells from CD25 knockout donor mice
      conferred little or no protection. We conclude that T cells with regulatory
      potential can develop, undergo thymic selection, and migrate to the peripheral
      lymphoid organs in the absence of IL-2, and do not protect from disease by means
      of IL-2 secretion. However, IL-2 signaling in regulatory T cells is essential for
      their protective function. Altogether, our results favor a model whereby IL-2
      induces regulatory T cell activity.

PMID- 12235218
TI  - A role for immune complexes in enhanced respiratory syncytial virus disease.
AB  - Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral
      pneumonia in infants and young children. Administration of a formalin inactivated
      vaccine against RSV to children in the 1960s resulted in increased morbidity and
      mortality in vaccine recipients who subsequently contracted RSV. This incident
      precluded development of subunit RSV vaccines for infants for over 30 years,
      because the mechanism of illness was never clarified. An RSV vaccine for infants
      is still not available. Here, we demonstrate that enhanced RSV disease is
      mediated by immune complexes and abrogated in complement component C3 and B cell
      deficient mice but not in controls. Further, we show correlation with the
      enhanced disease observed in children by providing evidence of complement
      activation in postmortem lung sections from children with enhanced RSV disease.

PMID- 12235219
TI  - Targeting the epidermal growth factor receptor for cancer therapy.

PMID- 12235220
TI  - Cancer prevention clinical trials.
AB  - Prevention of cancer through interventions based on sound scientific research
      remains an important strategy of oncology research at the National Cancer
      Institute (NCI). Reducing the burden of cancer in the United States is focused on
      clinical investigations in medical settings and public health intervention
      research on cancer risk factors regarding lifestyle and diet. Chemoprevention
      research at the NCI has progressed systematically to identify potential agents
      that reduce cancer risk and to develop public health strategies that take
      advantage of basic research results. In addition, advances in our understanding
      of molecular targets and pathways and our use of new and emerging technologies
      have become important tools for oncology research. Priority areas for
      chemoprevention research, identified from experimental and clinical research, are
      investigated in clinical trials to determine their ability to reduce cancer risk
      in selected populations or in the general population. Priority areas discussed in
      this review are the relationship of the arachidonic acid pathway to
      carcinogenesis, lung cancer prevention in former smokers, breast cancer
      prevention, and prostate cancer prevention. In addition, two lifestyle factors
      that have potential to influence cancer risk-obesity and functionally enhanced
      foods-are discussed in the context of their link between clinical and public
      health-related research.

PMID- 12235221
TI  - Chemotherapy for advanced non-small-cell lung cancer: who, what, when, why?
AB  - Despite the poor survival of patients with advanced (stage IIIB with pleural
      effusion or stage IV) non-small-cell lung cancer, the introduction of new
      chemotherapeutic agents has improved survival and quality of life with reduced
      toxicity compared with older cisplatin-based therapies. Randomized trials support
      the use of two-drug combinations for patients of all ages with performance status
      of 0 to 1. These two-drug combinations should contain at least one new agent.
      Some of these two-drug combinations may be acceptable in selected patients with a
      performance status of 2. Newer, targeted therapies hold promise to improve
      outcome without adding a great deal of additional toxicity.

PMID- 12235222
TI  - Complementary and alternative medicine use among women with breast cancer.
AB  - Complementary and alternative medicine (CAM) use has increased in recent years,
      with at least 42% of individuals in the United States using some form of CAM in
      1997. CAM includes a variety of modalities, ranging from nutritionally based
      interventions to behavioral techniques. This article reviews the status of CAM
      use among women with breast cancer. Patients are increasingly incorporating CAM
      into cancer prevention and treatment regimens. The prevalence of CAM use by
      breast cancer patients varies; however, it is typically higher than among
      individuals in the general population. Commonly used CAMs among women with breast
      cancer include nutritional/dietary supplements, relaxation strategies, and
      various types of social support groups. Apart from psychosocial interventions,
      little scientific evidence exists regarding the efficacy of CAM use for breast
      cancer patients. A common theme seen in many studies is that CAM use in women
      with breast cancer is highly correlated with increased psychosocial distress.

PMID- 12235224
TI  - Principles of clinical trial design.

PMID- 12235223
TI  - Safety issues in using complementary and alternative medicine.
AB  - PURPOSE: A number of reports have documented the apparent increasing popularity
      of complementary and alternative medicine (CAM) among cancer patients.
      Unfortunately, there are limited available published data regarding the potential
      toxicity of a variety of CAM strategies. METHODS: A review of the medical
      literature was undertaken to highlight the potential side effects of CAM.
      RESULTS: Although many CAM approaches are quite safe, both minor and major
      toxicities have been documented, including emesis, hypersensitivity reactions,
      cardiovascular events, neurologic dysfunction, hepatic and renal failure, and the
      development of malignant disease. CONCLUSION: It is important that oncologists
      are aware of what nonprescription CAM medications are being taking by their
      patients and have a basic understanding of the potential toxicities of these
      agents.

PMID- 12235226
TI  - Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical
      opportunities.
AB  - Degradation of the essential amino acid tryptophan along the kynurenine pathway
      (KP) yields several neuroactive intermediates, including the free radical
      generator 3-hydroxykynurenine, the excitotoxic N-methyl-D-aspartate (NMDA)
      receptor agonist quinolinic acid, and the NMDA and alpha7 nicotinic acetylcholine
      receptor antagonist kynurenic acid. The ambient levels of these compounds are
      determined by several KP enzymes, which in the brain are preferentially localized
      in astrocytes and microglial cells. Normal fluctuations in the brain levels of
      neuroactive KP intermediates might modulate several neurotransmitter systems.
      Impairment of KP metabolism is functionally significant and occurs in a variety
      of diseases that affect the brain. Pharmacological agents targeting specific KP
      enzymes are now available to manipulate the concentration of neuroactive KP
      intermediates in the brain. These compounds can be used to normalize KP defects,
      show remarkable efficacy in animal models of central nervous system disorders,
      and offer novel therapeutic opportunities.

PMID- 12235225
TI  - Anticancer drug discovery and development throughout the world.
AB  - This year's American Society of Clinical Oncology International Symposium devoted
      2 hours to a lively discussion of various aspects of anticancer drug discovery
      and development throughout the world. The scientific program started with an
      overview of efforts directed toward promoting international collaboration in
      natural product-derived anticancer drug discovery. This was followed by a
      discussion on the importance of interethnic differences and pharmacogenetics in
      anticancer drug development. Thereafter, this part of the program was completed
      by a description of the activities of the newly created Singapore-Hong Kong
      Australia Drug Development Consortium and an overview of the contribution of
      Japan to anticancer drug development. The logistics and regulatory aspects of
      clinical trials with new anticancer agents in different parts of the world were
      then presented, with an emphasis on Europe, North America, and Japan. The program
      was completed with a panel discussion of the efforts to harmonize the exchange of
      clinical data originating from one region of the globe with other territories,
      with input from official representatives of the United States Food and Drug
      Administration and the Medical Devices Evaluation Center of Japan.

PMID- 12235227
TI  - A novel approach for the increased delivery of pharmaceutical agents to
      peritoneum and associated lymph nodes.
AB  - A novel method for prolonging the retention of liposomes in the peritoneum while
      increasing liposome deposition in lymph nodes that drain the peritoneum is
      described. An aliquot (1 ml) of technetium-99m ((99m)Tc)-biotin-liposomes
      encapsulating blue dye was injected intraperitoneally in rats. Thirty minutes
      after administration of the (99m)Tc-blue-biotin-liposomes, five rats
      (experimental) were administered avidin (5 mg) intraperitoneally, whereas the
      remaining five rats served as controls. Scintigraphic images were acquired at
      baseline and 1 and 24 h after the liposome injection followed by a tissue
      biodistribution study. Images at 24 h clearly demonstrated very different
      distributions between the experimental and control animals. In experimental rats,
      most of the activity was visualized in the abdominal region, and in abdominal and
      mediastinal lymph nodes. The percentage of the injected dose (% ID) in the blood
      was significantly higher in the control group than in the experimental group
      (14.0 +/- 1.7 versus 0.17 +/- 0.03%; P < 0.001). The % ID in the spleen was also
      significantly greater for controls (23.3 +/- 3.9%) compared with the experimental
      group (0.78 +/- 0.8%; P = 0.001). Significant (99m)Tc activity was detected in
      blue-stained abdominal nodes (4.7%) and mediastinal nodes (2.3%) from the
      experimental animals, whereas no blue-stained nodes were detectable in the
      control animals. The intraperitoneal biotin-liposome/avidin delivery system
      described in this study could potentially be used for delivery of liposome
      encapsulated drugs to disease processes that become disseminated in the
      peritoneum such as metastatic ovarian, gastric, and colorectal cancer, as well as
      infectious peritonitis.

PMID- 12235228
TI  - Activation of delta-isoform of protein kinase C is required for oxidant-induced
      disruption of both the microtubule cytoskeleton and permeability barrier of
      intestinal epithelia.
AB  - Using monolayers of intestinal (Caco-2) cells, we showed that oxidants
      disassemble the microtubule cytoskeleton and disrupt barrier integrity
      (permeability) (Banan et al., 2000a). Because exposure of our parental cells to
      oxidants causes protein kinase C (PKC)-delta to be translocated to particulate
      fractions, we hypothesized that PKC-delta activation is required for these
      oxidant effects. Monolayers of parental Caco-2 cells were incubated with oxidant
      (H(2)O(2)) +/- modulators. Other cells were transfected with an inducible plasmid
      to stably overexpress PKC-delta or with a dominant negative plasmid to stably
      inhibit the activity of native PKC-delta. In parental cells, oxidants caused
      translocation of PKC-delta to the particulate (membrane + cytoskeletal)
      fractions, activation of PKC-delta isoform, increases in monomeric (S1) tubulin
      and decreases in polymerized (S2) tubulin, disruption of the microtubule
      cytoarchitecture, and loss of barrier integrity (hyperpermeability). In
      transfected cells, induction of PKC-delta overexpression by itself (3.5-fold over
      its basal level) led to oxidant-like disruptive effects. Disruption induced by
      PKC-delta overexpression was potentiated by oxidants. Overexpressed PKC-delta
      resided in particulate fractions, indicating its activation. Stable inhibition of
      native PKC-delta activity (98%) by dominant negative transfection substantially
      protected against all measures of oxidative disruption. We conclude that 1)
      oxidants induce loss of intestinal epithelial barrier integrity by disassembling
      the microtubules in large part through the activation of the PKC-delta isoform;
      and 2) overexpression and activation of PKC-delta is by itself a sufficient
      condition for disruption of these cytoskeleton and permeation pathways. Thus, PKC
      delta activation may play a key role in intestinal dysfunction in oxidant-induced
      diseases such as inflammatory bowel disease.

PMID- 12235229
TI  - Lithocholylcholine, a bile acid/acetylcholine hybrid, is a muscarinic receptor
      antagonist.
AB  - Previous work from our laboratory indicates that bile acids, specifically
      lithocholic acid conjugates, interact with muscarinic receptors on gastric chief
      cells. Structural similarities between acetylcholine and lithocholyltaurine
      suggest a potential molecular basis for their interaction with the same receptor.
      We synthesized a hybrid molecule consisting of the steroid nucleus of
      lithocholyltaurine and the choline moiety of acetylcholine. The new molecule,
      lithocholylcholine, is hydrolyzed by acetyl-cholinesterase. Lithocholylcholine
      inhibited binding of a cholinergic radioligand to Chinese hamster ovary cells
      expressing each of the five muscarinic receptor subtypes. The binding affinities
      (K(i); micromolar) of lithocholylcholine for these receptors were: M3 (1.0) > M1
      (2.7) > M2 (4.1) = M4 (4.9) > M5 (6.2). Lithocholylcholine inhibited
      intracellular signaling pathways mediated by interaction with M1, M2, and M3
      muscarinic receptors. Regarding M3 receptors, lithocholylcholine was 10-fold more
      potent than lithocholyltaurine in terms of binding affinity and inhibition of
      acetylcholine-induced increases in inositol phosphate formation and mitogen
      activated protein kinase phosphorylation. In a functional assay,
      lithocholylcholine inhibited acetylcholine-induced relaxation of rat aortic
      rings. These observations indicate that lithocholylcholine is a muscarinic
      receptor antagonist and provide further evidence that bile acids may have
      gastrointestinal signaling functions that extend beyond their effects on sterol
      metabolism, lipid absorption, and cholesterol elimination. Hybrid molecules
      created from bile acids and acetylcholine may be used to develop selective
      muscarinic receptor ligands.

PMID- 12235230
TI  - Effect of chronic administration of R-(+)-[2,3-Dihydro-5-methyl-3
      [(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1
      naphthalenyl)methanone mesylate (WIN55,212-2) or delta(9)-tetrahydrocannabinol on
      cannabinoid receptor adaptation in mice.
AB  - Agonist efficacy may influence the magnitude of neuroadaptation in response to
      chronic drug exposure. Chronic administration of either Delta(9)
      tetrahydrocannabinol (THC), a partial agonist, or R-(+)-[2,3-dihydro-5-methyl-3
      [(morpholinyl)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazinyl]-(1
      naphthalenyl)methanone mesylate (WIN55,212-2), a full agonist, for G protein
      activation produces tolerance to cannabinoid-mediated behaviors. The present
      study examined whether chronic administration of maximally tolerated doses of
      Delta(9)-THC and WIN55,212-2 produces similar cannabinoid receptor
      desensitization and down-regulation. Mice were treated with escalating doses of
      agonist for 15 days, with final doses of 160 mg/kg Delta(9)-THC and 48 mg/kg
      WIN55,212-2. Tolerance to cannabinoid-mediated hypoactivity, hypothermia, and
      antinociception was found after treatment with Delta(9)-THC or WIN55,212-2. In
      autoradiographic studies, cannabinoid-stimulated guanosine 5'-O-(3
      [(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding was significantly decreased
      in all regions of Delta(9)-THC- and WIN55,212-2-treated brains. In addition,
      Delta(9)-THC-treated brains showed greater desensitization in some regions than
      WIN55,212-2-treated brains. Concentration-effect curves for cannabinoid
      stimulated [(35)S]GTPgammaS binding confirmed that decreases in the hippocampus
      resulted from loss of maximal effect in both WIN55,212-2- and Delta(9)-THC
      treated mice. In the substantia nigra, the E(max) decreased and the EC(50) value
      increased for agonist stimulation of [(35)S]GTPgammaS binding in Delta(9)-THC
      treated mice. [(3)H]N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)
      4-methyl-1H-pyrazole-3-carboxamide (SR141716A) binding was decreased in all brain
      regions in Delta(9)-THC- and WIN55,212-2-treated mice, with no difference between
      treatment groups. These results demonstrate that chronic treatment with either
      the partial agonist Delta(9)-THC or the full agonist WIN55,212-2 produces
      tolerance to cannabinoid-mediated behaviors, as well as cannabinoid receptor
      desensitization and down-regulation. Furthermore, Delta(9)-THC produced greater
      desensitization than WIN55,212-2 in some regions, indicating that agonist
      efficacy is one determinant of cannabinoid receptor desensitization in brain.

PMID- 12235231
TI  - Nonpeptide antagonists of AT1 receptor for angiotensin II delay the onset of
      acute respiratory distress syndrome.
AB  - We have previously reported that losartan, a selective antagonist of AT1
      receptors for angiotensin II (AII), strongly suppresses the activation of
      neutrophils by N-formylmethionyl-leucyl-phenylalanine (fMLP) through a mechanism
      that does not involve inhibition of AT1 receptors. Herein, we analyze whether
      losartan would prevent the development of the acute respiratory distress syndrome
      (ARDS) triggered by lung bacterial infection. We found that losartan (0.2-200
      microg/kg/min) delays the onset of ARDS in Wistar rats challenged by i.t.
      instillation of Bordetella bronchiseptica. Although this effect was associated
      with a significant inhibition of lung-neutrophil recruitment, lung bacterial
      clearance was not impaired but rather, it was significantly improved. We also
      found that another nonpeptide AT1 receptor blocker, irbesartan, exerted similar
      effects to losartan, i.e., it was also able to inhibit neutrophil activation by
      fMLP and to delay the onset of ARDS in B. bronchiseptica-challenged rats. Neither
      the inhibitor of angiotensin-converting enzyme captopril, nor the nonselective
      peptide inhibitor of AII receptors saralasin reproduced these effects. Our data
      are consistent with the possibility that nonpeptide AT1 receptor blockers delay
      the onset of ARDS triggered by bacterial infection through a mechanism dependent,
      at least in part, on their ability to prevent neutrophil activation by N-formyl
      peptides.

PMID- 12235232
TI  - PPA250 [3-(2,4-difluorophenyl)-6-[2-[4-(1H-imidazol-1-ylmethyl) phenoxy]ethoxy]-2
      phenylpyridine], a novel orally effective inhibitor of the dimerization of
      inducible nitric-oxide synthase, exhibits an anti-inflammatory effect in animal
      models of chronic arthritis.
AB  - Nitric oxide (NO) plays an important role in various physiological processes.
      Excessive NO production is closely related to inflammatory and autoimmune
      diseases such as septic shock and rheumatoid arthritis. Suppression of excess NO
      formation in participating cells may be helpful in improving disease status. In
      this study, we examined the effects of a newly synthesized imidazole derivative,
      3-(2,4-difluorophenyl)-6-[2-[4-(1H-imidazol-1-ylmethyl) phenoxy]ethoxy]-2
      phenylpyridine (PPA250), on NO production in vitro and in vivo, as well as on the
      dimerization of inducible nitric-oxide synthase (iNOS). PPA250 at concentrations
      of 25 nM and higher inhibited NO production in activated mouse macrophage-like
      RAW264.7 cells. The IC(50) was approximately 82 nM. Western blot analysis
      revealed that PPA250 prevents dimerization of iNOS but has no effect on
      transcription and translation. In addition, oral administration of PPA250 (10
      mg/kg and higher) reduced the NO concentration in serum from mice in which sepsis
      was induced by bacterial lipopolysaccharide. Since the inhibitory activity was
      observed not only in vitro but also in vivo, we examined the therapeutic
      potential of PPA250 in two animal models of arthritis, collagen-induced arthritis
      in mice and adjuvant arthritis in rats. PPA250 suppressed the development of a
      destructive polyarthritis in both models after the appearance of clinical signs.
      These results indicate that inhibitors of iNOS homodimerization, including
      PPA250, could be useful therapeutic agents for inflammatory and autoimmune
      diseases, such as rheumatoid arthritis, in which NO is involved.

PMID- 12235233
TI  - Effect of cyclosporine a on hepatic compensatory growth: role of calcium status.
AB  - Cyclosporine A (CsA) has been reported to positively influence hepatic
      compensatory growth (HCG) in normal animals. The role of calcium in the CsA
      mediated influence on HCG was studied in normal and in chronically hypocalcemic
      rats, a model in which HCG is perturbed. CsA (3.33 mg/kg/day for 10 days) was
      administered before 2/3 partial hepatectomy (PHx). CsA did not influence serum
      Ca(2+) but significantly increased concentrations of the vitamin D hormone
      calcitriol. After PHx in normal animals, CsA accelerated DNA synthesis without
      influencing liver weight restitution, suggesting that its main effect was to
      mediate an accelerated progression through the cell cycle G(0) to G(1)/S
      phase(s). In hypocalcemic rats, CsA did not influence DNA synthesis, but
      normalization of circulating calcium alone accelerated DNA synthesis but
      abrogated the stimulatory effect of CsA, indicating that CsA could not
      superimpose its stimulatory effect on the calcium effect. In vitro investigation
      on the CsA mechanisms of action revealed a dose-dependent increase in hepatocyte
      basal resting cytoplasmic Ca(2+) and an increase in inositol-1,4,5-trisphosphate
      sensitive Ca(2+) pool, which was dependent on the presence of normal
      extracellular Ca(2+) during CsA exposure. CsA also mediated a significant
      increase in cellular Ca(2+) mobilization by phenylephrine, vasopressin, and
      epidermal growth factor (EGF) in the presence of extracellular Ca(2+)
      concentration. Our data, therefore, demonstrate that CsA accelerates HCG after
      PHx by, in part, increasing the cellular Ca(2+) pools and the response to EGF and
      Ca(2+)-mobilizing hormones known to be comitogens for hepatocytes.

PMID- 12235234
TI  - Analgesic effects of intrathecal administration of P2Y nucleotide receptor
      agonists UTP and UDP in normal and neuropathic pain model rats.
AB  - Recent electrophysiological, behavioral, and biochemical studies revealed that
      ATP plays a role in facilitating spinal pain transmission via ionotropic P2X
      nucleotide receptors, although the involvement of metabotropic P2Y nucleotide
      receptors remains unclear. In the present study, we examined the effects of i.t.
      administration of P2Y receptor agonists UTP, UDP, and related compounds on
      nociception in normal rats and tactile allodynia in a neuropathic pain model. In
      the paw pressure test using normal rats, i.t. administration of UTP (30 and 100
      nmol/rat) and UDP (30 and 100 nmol/rat), but not UMP (100 nmol/rat) or uridine
      (100 nmol/rat), significantly elevated the mechanical nociceptive thresholds,
      whereas ATP (30 and 100 nmol/rat) and alpha,beta-methylene-ATP (10 and 30
      nmol/rat) lowered them. Similarly, in the tail-flick test, UTP (10, 30, and 100
      nmol/rat) and UDP (100 nmol/rat) significantly prolonged the thermal nociceptive
      latency. In the von Frey filament test on normal rats, UTP (100 nmol/rat) and UDP
      (100 nmol/rat) produced no allodynia to the tactile stimulus, whereas ATP (100
      nmol/rat) induced a significant and long-lasting tactile allodynia. In the
      neuropathic pain model, in which the sciatic nerves of rats were partially
      ligated, UTP (30 and 100 nmol/rat) and UDP (30 and 100 nmol/rat) produced
      significant antiallodynic effects. Furthermore, UTP (100 nmol/rat) and UDP (100
      nmol/rat) caused no motor deficit in the inclined plane test. Taken together,
      these results suggest that the activation of UTP-sensitive P2Y(2) and/or P2Y(4)
      receptors and the UDP-sensitive P2Y(6) receptor, in contrast to P2X receptors,
      produces inhibitory effects on spinal pain transmission.

PMID- 12235235
TI  - Potent suppression of proliferation of a10 vascular smooth muscle cells by
      combined treatment with lovastatin and 3-allylfarnesol, an inhibitor of protein
      farnesyltransferase.
AB  - Statins, which inhibit 3-hydroxy-3-methylglutaryl-CoA reductase and thus the
      synthesis of cholesterol, are remarkably effective in the treatment of
      cardiovascular disease. In addition to their favorable effect on lipid profile,
      these drugs may also prevent the proliferation of vascular smooth muscle that is
      characteristic of atherosclerosis. We hypothesize that statins prevent the post
      translational prenylation, and thus inhibit the function, of critical small
      GTPases in vascular smooth muscle cells. We have therefore assayed the effect of
      lovastatin on both the growth of A10 vascular smooth muscle cells and the status
      of their Ras and RhoB proteins. We find that < or =1 microM lovastatin potently
      inhibits the proliferation of A10 cultures, and higher concentrations (> or =3
      microM) induce apoptosis. We have also tested the effect of 3-allylfarnesol (3
      alFOH), an inhibitor of farnesyl transferase (FTI). The data show that although >
      or =10 microM 3-alFOH is required for a cytostatic effect, the action of 3 microM
      3-alFOH can be greatly potentiated by even nanomolar levels of lovastatin. We
      also find that lovastatin and 3-alFOH exhibit synergism to cause the up
      regulation and relocalization of RhoB from the membrane to cytosolic
      compartments. This relocalization of RhoB, which is presumed to reflect an
      inhibition of its prenylation, correlates with the proapoptotic activities of
      combined 3-alFOH and lovastatin treatment. These data suggest that RhoB may be a
      valuable pharmacological target in cardiovascular disease, and that combinations
      of statins and certain FTIs may be of value in treatment of disorders that are
      characterized by excess cell proliferation.

PMID- 12235236
TI  - Inhibition of glucose- and calcium-induced insulin secretion from betaTC3 cells
      by novel inhibitors of protein isoprenylation.
AB  - The majority of low molecular weight G proteins undergoes a series of post
      translational modification steps, e.g., isoprenylation, at their C-terminal
      cysteine, which seem to be critical for the transport of the modified proteins to
      the membrane sites for interaction with their respective effector proteins. Using
      lovastatin, an inhibitor of mevalonic acid, and hence, isoprenoid biosynthesis,
      we demonstrated previously that protein isoprenylation is critical for
      physiological insulin secretion from normal rat islets. Herein, we used more
      selective synthetic inhibitors of protein prenylation to examine their effects on
      glucose- and calcium-mediated insulin secretion from betaTC3 cells. Both 3-allyl-
      and vinylfarnesols, which inhibit and/or modulate protein farnesyl transferases,
      significantly (80-95%) inhibited glucose- and KCl-stimulated insulin secretion
      from these cells. In a similar manner, the allyl and vinyl forms of
      geranylgeraniol, reagents targeted toward protein geranylation, attenuated
      insulin secretion elicited by glucose and KCl. Furthermore, manumycin A, a
      natural inhibitor of protein farnesylation, and geranylgeranyl transferase
      inhibitor-2147 (GGTI-2147), a peptidomimetic inhibitor of protein
      geranylgeranylation, also inhibited glucose- and KCl-induced insulin secretion to
      comparable degrees. Treatment of betaTC3 cells with either 3-vinylfarnesol or 3
      vinyl geranylgeraniol resulted in accumulation of unprenylated proteins in the
      cytosolic fraction. These data further support our original formulation that
      inhibition of isoprenylation of small molecular weight G proteins might impede
      their interaction with their putative effectors, which may be required for
      physiological insulin secretion.

PMID- 12235237
TI  - Molecular cloning and functional characterization of a unique mammalian cardiac
      Na(v) channel isoform with low sensitivity to the synthetic inactivation
      inhibitor (-)-(S)-6-amino-alpha-[(4-diphenylmethyl-1-piperazinyl)-methyl]-9H
      purine-9-ethanol (SDZ 211-939).
AB  - Cardiac voltage-dependent sodium channels (Na(v)) are drug targets for synthetic
      inactivation inhibitors typified by (+/-)-4- [3-(4-diphenylmethyl-1-piperazinyl)
      2-hydroxy propoxy]-1H-indole-2-carbonitrile (DPI 201-106), of which the molecular
      mode of action is not yet defined. The previous observation by Mevissen and
      coworkers in 2001 of the electrophysiological ineffectiveness of DPI 201-106 in
      the bovine heart, in contrast to other species, offers the opportunity for
      investigating these open questions. We now report about the molecular cloning,
      expression in Xenopus laevis oocytes, and electrophysiological characterization
      of a unique bovine heart sodium channel. Although the predicted 2022-amino acid
      bovine heart sodium channel (bH1) shares 92% identity with the rat and human
      isoforms and normal gating properties, it displays drastically reduced
      sensitivity to (-)-(S)-6-amino-alpha-[(4-diphenylmethyl-1-piperazinyl)-methyl]-9H
      purine-9-ethanol (SDZ 211-939). Experimental results with Anemonia sulcata toxin
      II (0.1-2.5 microM) exclude the possibility of an overall insensitivity of this
      isoform to various sodium channel modulators. The binding of SDZ 211-939 seems to
      be largely unaffected (EC(50) of 10.3 and 10.6 microM for bovine and rat
      isoforms, respectively) but the corresponding efficacy in bovine (V(m) of 0.15)
      is approximately 5 times smaller compared with the rat heart isoform (V(m) of
      0.69). The comparison of the primary structure of bH1 to other sodium channels
      and the gating properties obtained in presence or absence of SDZ 211-939 revealed
      a high degree of similarity. Whether the mechanism of channel modulation depends
      on the interaction of synthetic modulators with some possibly voltage-independent
      part of the inactivation machinery needs to be determined.

PMID- 12235238
TI  - Muscarinic agonist-mediated increases in serum corticosterone levels are
      abolished in m(2) muscarinic acetylcholine receptor knockout mice.
AB  - Muscarinic acetylcholine receptors (M(1)-M(5)) regulate many key functions in the
      central and peripheral nervous system. Due to the lack of receptor subtype
      selective ligands, however, the physiological roles of individual muscarinic
      receptor subtypes remain to be determined. In this study, we examined the effects
      of the muscarinic M(2)/M(4) receptor-preferring agonist [5R-(exo)]-6-[4-butylthio
      1,2,5-thiadiazol-3-yl]-1-azabicyclo-[3.2.1]-octane (BuTAC) on serum
      corticosterone levels in M(2) and M(4) receptor single knockout (KO) and M(2,4)
      receptor double KO mice. Responses were compared with those obtained with the
      corresponding wild-type (WT) mice. BuTAC (0.03-0.3 mg/kg s.c.) dose dependently
      and significantly increased serum corticosterone concentrations in WT mice to 5
      fold or greater levels compared with vehicle controls. In muscarinic M(2) and
      M(2,4) KO mice, however, BuTAC had no significant effect on corticosterone
      concentrations at doses of 0.1, 0.3, and 1 mg/kg s.c. In both WT and muscarinic
      M(4) KO mice increases in serum corticosterone concentrations induced by BuTAC
      (0.1 and 0.3 mg/kg) were not significantly different and were blocked by
      scopolamine. In summary, the muscarinic M(2,4)-preferring agonist BuTAC had no
      effect on corticosterone levels in mice lacking functional muscarinic M(2)
      receptors. These data suggest that the muscarinic M(2) receptor subtype mediates
      muscarinic agonist-induced activation of the hypothalamic-pituitary
      adrenocortical axis in mice.

PMID- 12235239
TI  - Biological activity of a novel nonpeptide antagonist to the interleukin-6
      receptor 20S,21-epoxy-resibufogenin-3-formate.
AB  - Interleukin (IL)-6 is a key mediator in the regulation and coordination of the
      immune response and participates in pathogenesis of cancer cachexia, autoimmune
      disease, and postmenopausal osteoporosis. In the course of a screening program
      aimed at IL-6 inhibitor from natural products, we isolated 20S,21-epoxy
      resibufogenin-3-formate (ERBF) from bufadienolide and examined the effect of ERBF
      on activities of various cytokines. ERBF dose dependently suppressed IL-6
      activity and caused a parallel rightward shift of dose-response curves to IL-6 at
      concentrations of 0.03 to 10 ng/ml. Analysis of data yields a pA(2) of 5.12 and a
      slope of 0.99. Selectivity of ERBF on activity of cytokines was examined using
      cytokine-dependent cell lines. ERBF did not affect IL-2-dependent growth of CTLL
      2 cells, IL-3-dependent growth of Baf3 cells, or tumor necrosis factor (TNF)alpha
      induced growth suppression in TNFalpha-sensitive L929 cells. ERBF also did not
      affect IL-4-stimulated expression of FcepsilonR II receptor (CD23) in U-937
      cells, the IL-8-induced chemotaxis of human neutrophils, or nerve growth factor
      stimulated neuronal differentiation in PC-12 cells. In contrast, ERBF dose
      dependently suppressed IL-6-induced neuronal differentiation in PC-12 cells.
      Furthermore, ERBF suppressed only IL-6-induced osteoclast formation without
      affecting osteoclast formation induced by IL-11, leukemia inhibitory factor, and
      1alpha,25-dihydroxyvitamin D(3). In receptor binding assay, unbound (free) IL-6
      was increased in a dose-dependent manner by pretreatment with ERBF on IL-6
      receptor (IL-6R), suggesting that ERBF suppresses binding of IL-6 to IL-6R. These
      results clearly indicate that ERBF is a novel specific small molecule to show IL
      6 receptor antagonist activity.

PMID- 12235240
TI  - Peptide antagonists of ethanol inhibition of l1-mediated cell-cell adhesion.
AB  - Ethanol inhibits cell-cell adhesion mediated by the L1 cell adhesion molecule. 1
      Octanol potently antagonizes this cellular action of ethanol and also prevents
      ethanol-induced dysmorphology and cell death in mouse whole embryo culture.
      NAPVSIPQ (NAP) and SALLRSIPA (SAL) are active peptide fragments of two
      neuroprotective proteins: activity-dependent neuroprotective protein and activity
      dependent neurotrophic factor. NAP and SAL are neuroprotective at femtomolar
      concentrations against a variety of neurotoxins and also prevent ethanol
      teratogenesis in mice. To explore the cellular basis for this action, we asked
      whether NAP and SAL antagonize ethanol inhibition of L1 adhesion. Aggregation
      assays were carried out in ethanol-sensitive, human L1-transfected NIH/3T3 cells
      in the absence and presence of NAP and SAL. Neither NAP nor SAL altered L1
      adhesion or L1 expression; however, both peptides potently and completely
      antagonized the inhibition of L1 adhesion by 100 mM ethanol (EC(50): NAP, 6 x 10(
      14) M; SAL, 4 x 10(-11) M). NAP also antagonized ethanol inhibition of cell-cell
      adhesion in bone morphogenetic protein-7-treated NG108-15 cells. In L1-expressing
      NIH/3T3 cells, SAL antagonism was reversible and could be overcome by increasing
      concentrations of ethanol. In contrast, NAP antagonism was irreversible and could
      not be overcome by increasing agonist concentration. Two scrambled NAP peptides
      (ASPNQPIV and PNIQVASP) were not antagonists at concentrations as high as 10(-7)
      M. Thus, two structurally unrelated classes of compounds, alcohols and small
      polypeptides, share two common actions: antagonism of ethanol inhibition of L1
      mediated cell adhesion and prevention of ethanol teratogenesis. These findings
      support the hypothesis that ethanol inhibition of L1 adhesion contributes to
      ethanol teratogenesis.

PMID- 12235241
TI  - Role of adenosine A(1) receptor in angiotensin II- and norepinephrine-induced
      renal vasoconstriction.
AB  - We investigated the contributions of adenosine A(1) receptors to angiotensin II-
      and norepinephrine-induced renal vasoconstriction. Intrarenal administrations of
      angiotensin II (3, 10, and 30 ng) or norepinephrine (100 and 500 ng) produced
      dose-dependent renal vasoconstriction in anesthetized dogs. Under resting
      conditions, angiotensin II (30 ng) and norepinephrine (500 ng) significantly
      decreased renal blood flow by -43 +/- 3 and -19 +/- 2%, respectively (n = 21).
      Intra-arterial infusion of adenosine (5 microg/kg/min) significantly augmented
      renal blood flow responses to both angiotensin II and norepinephrine (-64 +/- 4
      and -45 +/- 14%, n = 7). Renal blood flow responses to angiotensin II and
      norepinephrine were also augmented by inhibition of cellular uptake of adenosine
      with dipyridamole (10 microg/kg/min, n = 6). Blockade of adenosine A(1) receptors
      with 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902; 10 microg/kg/min) did
      not alter basal renal blood flow but significantly attenuated angiotensin II- and
      norepinephrine-induced renal vasoconstriction (-34 +/- 6 and -9 +/- 3%, n = 7).
      Furthermore, KW-3902 completely prevented augmentation of renal blood flow
      responses to angiotensin II and norepinephrine produced by adenosine or
      dipyridamole (n = 7 and 6, respectively). Administrations of angiotensin II (30
      ng) or norepinephrine (500 ng) into the common carotid artery significantly
      decreased carotid blood flow by -20 +/- 5 and -41 +/- 10%, respectively; however,
      neither adenosine (5 microg/kg/min) nor KW-3902 (10 microg/kg/min) affected the
      carotid blood flow responses to angiotensin II and norepinephrine (n = 5,
      respectively). Adenosine concentrations in dialysates were not significantly
      changed by administrations of angiotensin II (from 19 +/- 3 to 24 +/- 4 nM, n =
      6) or norepinephrine (from 16 +/- 3 to 19 +/- 3 nM, n = 6). These results suggest
      that basal interstitial adenosine levels influence both angiotensin II and
      norepinephrine-induced vasoconstriction via A(1) receptors in the kidney but not
      in the area drained by the common carotid artery. The responses of adenosine to
      angiotensin II- and norepinephrine-induced renal vasoconstriction may not be
      mediated through de novo intrarenal adenosine accumulation due to angiotensin II-
      and norepinephrine-induced renal vasoconstriction.

PMID- 12235242
TI  - DNA damage induces a novel p53-survivin signaling pathway regulating cell cycle
      and apoptosis in acute lymphoblastic leukemia cells.
AB  - Survivin is a novel member of the inhibitor of apoptosis protein (IAP) family.
      Here we report that the chemotherapeutic drug doxorubicin, a DNA-damaging agent,
      activates a p53-survivin signaling pathway inducing cell cycle arrest and
      apoptosis in childhood acute lymphoblastic leukemia (ALL). Treatment of wild-type
      (wt) p53 ALL cells (EU-3 cell line) with doxorubicin caused accumulation of p53,
      resulting in dramatic down-regulation of survivin, depletion of cells in G(2)/M,
      and apoptosis (increased sub-G(1) compartment). In contrast, doxorubicin
      treatment of mutant (mut) p53 cells (EU-6/ALL line) up-regulated survivin and
      induced G(2)/M arrest without inducing apoptosis. However, treating EU-6 with
      anti-survivin antisense resensitized these cells to doxorubicin, resulting in
      apoptosis. With a p53-null cell line (EU-4), although doxorubicin treatment
      arrested cells in G(2)/M, survivin expression was unchanged, and cells underwent
      only limited apoptosis. However, re-expression of wt-p53 in EU-4 cells could
      restore the doxorubicin-p53-survivin pathway, resulting in significantly
      decreased survivin expression and increased apoptosis in these cells after
      doxorubicin treatment. Following cotransfection of p53-null EU-4 cells with
      survivin promoter-luciferase constructs and either wt-p53 or different mut-p53
      expression vectors, wt-p53 inhibited survivin promoter activity; p53-mediated
      inhibition could be abrogated by overexpression of murine double minute2 (MDM2)
      protein. Together, these studies define a novel p53-survivin signaling pathway
      activated by DNA damage that results in down-regulation of survivin, cell cycle
      arrest, and apoptosis. Furthermore, our data indicate that loss of wt-p53
      function in tumor cells may contribute to up-regulation of survivin and
      resistance to DNA-damaging agents.

PMID- 12235243
TI  - In vivo characterization of the mitochondrial selective K(ATP) opener (3R)-trans
      4-((4-chlorophenyl)-N-(1H-imidazol-2-ylmethyl)dimethyl-2H-1-benzopyran-6
      carbonitril monohydrochloride (BMS-191095): cardioprotective, hemodynamic, and
      electrophysiological effects.
AB  - Recent studies have shown the importance of mitochondrial ATP-sensitive potassium
      channels (K(ATP)) in cardioprotection, and studies in vitro have shown that the
      benzopyran analog (3R)-trans- 4-((4-chlorophenyl)-N-(1H-imidazol-2
      ylmethyl)dimethyl-2H-1-benzopyran-6-carbonitril monohydrochloride (BMS-191095) is
      a selective mitochondrial K(ATP) opener with cardioprotective activity. The goal
      of this study was to show selective cardioprotection for BMS-191095 in vivo
      without hemodynamic or cardiac electrophysiological effects expected for
      nonselective K(ATP) openers. BMS-191095 reduced infarct size in anesthetized dogs
      (90-min ischemia + 5-h reperfusion) in a dose-dependent manner (ED(25) = 0.4
      mg/kg i.v.) with efficacious plasma concentrations of 0.3 to 1.0 microM, which
      were consistent with potency in vitro. None of the doses of BMS-191095 tested
      caused any effect on peripheral or coronary hemodynamic status. Further studies
      in dogs showed no effects of BMS-191095 on cardiac conduction or action potential
      configuration within the cardioprotective dose range. In a programmed electrical
      stimulation model, BMS-191095 showed no proarrhythmic effects, which is
      consistent with its lack of effects on cardiac electrophysiological status. BMS
      191095 is a potent and efficacious cardioprotectant that is devoid of hemodynamic
      and cardiac electrophysiological side effects of first generation K(ATP) openers,
      which open both sarcolemmal and mitochondrial K(ATP). Selective opening or
      activation of mitochondrial K(ATP) seems to be a potentially effective strategy
      for developing well tolerated and efficacious K(ATP) openers.

PMID- 12235244
TI  - Primaquine-induced hemolytic anemia: effect of 6-methoxy-8-hydroxylaminoquinoline
      on rat erythrocyte sulfhydryl status, membrane lipids, cytoskeletal proteins, and
      morphology.
AB  - Previous studies have shown that 6-methoxy-8-hydroxylaminoquinoline (MAQ-NOH), an
      N-hydroxy metabolite of the antimalarial drug, primaquine, is a direct-acting
      hemolytic agent in rats. To investigate the mechanism underlying this hemolytic
      activity, the effects of hemotoxic concentrations of MAQ-NOH on rat erythrocyte
      sulfhydryl status, membrane lipids, skeletal proteins, and morphology have been
      examined. Treatment of rat erythrocytes with a TC(50) concentration of MAQ-NOH
      (350 microM) caused only a modest and transient depletion of reduced glutathione
      (GSH) (~30%), which was matched by modest increases in the levels of glutathione
      disulfide and glutathione-protein mixed disulfides. Lipid peroxidation, as
      measured by thiobarbituric acid-reactive substances and F(2)-isoprostane
      formation, was induced in a concentration-dependent manner by MAQ-NOH. However,
      the formation of disulfide-linked hemoglobin adducts on membrane skeletal
      proteins and changes in erythrocyte morphology were not observed. These data
      suggest that hemolytic activity results from peroxidative damage to the lipid of
      the red cell membrane and is not dependent on skeletal protein thiol oxidation.
      However, when red cell GSH was depleted (>90%) by titration with diethyl maleate,
      hemolytic activity of MAQ-NOH was markedly enhanced. Of interest, exacerbation of
      hemotoxicity was not matched by increases in lipid peroxidation, but by the
      appearance of hemoglobin-skeletal protein adducts. Collectively, the data are
      consistent with the concept that MAQ-NOH may operate by more than one mechanism;
      one that involves lipid peroxidation in the presence of normal amounts of
      erythrocytic GSH, and one that involves protein oxidation in red cells with low
      levels of GSH, such as are seen in individuals with glucose-6-phosphate
      dehydrogenase deficiency.

PMID- 12235245
TI  - Postischemic recovery and oxidative stress are independent of nitric-oxide
      synthases modulation in isolated rat heart.
AB  - During myocardial ischemia and reperfusion, nitric oxide ((.)NO) was shown to
      exert either beneficial or detrimental effects. Uncoupled (.)NO synthases (NOS)
      can generate superoxide anion under suboptimal concentrations of substrate and
      cofactors. The aim of our study was to investigate the role of NOS modulation on
      1) the evolution of functional parameters and 2) the amount of free radicals
      released during an ischemia-reperfusion sequence. Isolated perfused rat hearts
      underwent 30 min of total ischemia, followed by 30 min of reperfusion in the
      presence of N(G)-nitro-D- or L-arginine methyl ester (NAME, 100 microM) or of D-
      or L-arginine (3 mM). Functional parameters were recorded and coronary effluents
      were analyzed with electron spin resonance to identify and quantify the amount of
      alpha-phenyl-N-tert-butylnitrone spin adducts produced during reperfusion. The
      antioxidant capacities of the compounds were determined with the oxygen radical
      absorbance capacity test. L-NAME-treated hearts showed a reduction of coronary
      flow and contractile performance, although neither L-NAME nor L-arginine improved
      the recovery of coronary flow, left end diastolic ventricular pressure, rate
      pressure product, and duration of reperfusion arrhythmia, compared with their D
      specific enantiomers. A large and long-lasting release of alkyl/alkoxyl radicals
      was detected upon reperfusion, but no differences of free radical release were
      observed between D- and L-NAME or D- and L-arginine treatment. These results may
      indicate that, in our experimental conditions, cardiac NOS might not be a major
      factor implicated in the oxidative burst that follows a global myocardial
      ischemia.

PMID- 12235246
TI  - Effects of folate treatment and homocysteine lowering on resistance vessel
      reactivity in atherosclerotic subjects.
AB  - Hyperhomocysteinemia is associated with arterial hypertension and endothelial
      dysfunction in healthy humans. Placebo-controlled vitamin intervention studies
      cannot distinguish intrinsic actions of homocysteine (tHcy) and folate
      concentrations on the endothelium. The present two-period crossover study
      investigates the effects of tHcy lowering through oral folic acid on antioxidant
      status and resistance vessel reactivity in patients with established coronary
      artery disease (CAD). We investigated 27 male patients with angiographically
      documented multivessel CAD aged 50 (range 46-56) years. Resistance vessel
      reactivity was assessed by measurement of postischemic reactive hyperemia (RH) in
      the forearm using venous occlusion plethysmography at baseline, after 6 weeks of
      treatment with 5 mg of oral folic acid, and after a washout period of another 6
      weeks. Plasma folate increased 3.49-fold with a mean tHcy reduction of 21.3%.
      Peak reactivity of resistance vessels improved significantly (18.97-23.60 ml/min(
      1) per 100 ml; P = 0.01) with unchanged total antioxidant status (TAS; 0.912
      0.944 microM; P = 0.4). This effect was limited to subjects (n = 14) with a tHcy
      reduction >2 microM (median reduction, 14.4-9.6 microM, P < 0.001). In the 13
      subjects with a below-median reduction, tHcy remained unaltered (9.7-9.6 microM,
      P = 0.88) and TAS increased significantly (0.923-1.055 microM, P = 0.006),
      whereas RH peak flow was not affected (20.22-22.99 ml/min(-1) per 100 ml, P =
      0.28). Homocysteine lowering >2 microM through folic acid supplementation
      improves resistance vessel reactivity in patients with CAD. Our data support the
      hypothesis that homocysteine lowering may have intrinsic vasoprotective effects
      largely independent of folate.

PMID- 12235247
TI  - Tyrosine kinase inhibitors suppress the growth of non-hodgkin B lymphomas.
AB  - Non-Hodgkin lymphomas usually become resistant to chemotherapy and relapse due to
      the their intense antiapoptotic robustness. Furthermore, the slow growth of these
      malignancies limits the effectiveness of drugs aimed mainly at the proliferative
      pathways. Because protein tyrosine kinases (PTKs) play a key role in both
      proliferative and antiapoptotic pathways we screened our library of PTK
      inhibitors for agents that induce growth arrest and apoptosis in non-Hodgkin B
      cell lymphoma cell lines. Herein, we describe the identification of a family of
      PTK inhibitors whose most potent member is AGL 2592. This agent induces growth
      arrest and massive apoptosis in a number of non-Hodgkin lymphoma cell lines. We
      also show that the lymphoma cell lines are much more sensitive to this class of
      agents compared with other malignant carcinoma cells. AGL 2592 induces a dose
      dependent and time-dependent inhibition of tyrosine phosphorylation of numerous
      proteins, including Stat3, and an increase of Bcl-2 phosphorylation, both
      biochemical hallmarks of growth inhibition and apoptosis.

PMID- 12235248
TI  - Stereoselective metabolism of bufuralol racemate and enantiomers in human liver
      microsomes.
AB  - A new HPLC method was developed using a chiral column to efficiently separate
      four 1"-hydroxybufuralol (1"-OH-BF) diastereomers that are major metabolites of
      bufuralol (BF). Employing this method, we examined diastereomer selectivity in
      the formation of 1"-OH-BF from BF racemate or enantiomers in four individual
      samples of human liver microsomes. Three different human liver microsomes showed
      a selectivity of 1"R-OH < 1"S-OH for BF enantiomers, which was similar to that of
      recombinant CYP2D6 expressed in insect cell microsomes, whereas one human liver
      microsomal fraction yielded a selectivity of 1"R-OH > 1"S-OH for BF enantiomers,
      which was similar to those of recombinant CYP2C19 expressed in insect cell
      microsomes. Recombinant CYP1A2 and CYP3A4 showed a selectivity similar to that of
      CYP2D6, but their BF 1"-hydroxylase activities were much lower than those of
      CYP2D6. In inhibition studies, quinidine, a known CYP2D6 inhibitor, markedly
      inhibited BF 1"-hydroxylation in the fractions of human liver microsomes that
      showed the CYP2D6-type selectivity. Furthermore, omeprazole, a known CYP2C19
      inhibitor, efficiently suppressed the formation of 1"-OH-BF diastereomers from BF
      in the microsomal fraction that showed the CYP2C19-type selectivity. From these
      results, we concluded that the diastereomer selectivity in the formation of 1"-OH
      BF from BF differs between CYP2D6 and CYP2C19, both of which can be determinant
      enzymes in the diastereoselective 1"-hydroxylation of BF in human liver
      microsomes.

PMID- 12235250
TI  - Nociceptin/orphanin FQ modulation of ionic conductances in rat basal forebrain
      neurons.
AB  - Nociceptin/orphanin FQ (N/OFQ) is an endogenous opioid-like heptadecapeptide that
      plays an important role in a variety of physiological functions. N/OFQ and its
      receptor opioid receptor-like orphan receptor-1 are abundant in the diagonal band
      of Broca (DBB), a basal forebrain nucleus where the loss of cholinergic neurons
      is linked to memory and spatial learning deficits. In the whole animal, central
      injections of N/OFQ have been shown to disrupt spatial learning. In this study,
      we investigated the basis for these behavioral observations by examining the
      cellular effects of N/OFQ on chemically identified DBB neurons. Whole cell patch
      clamp recordings were performed on enzymatically dissociated DBB neurons. Under
      voltage-clamp conditions, bath application of N/OFQ (10 pM-1 microM) resulted in
      a dose-dependent depression of whole cell currents. Single cell reverse
      transcription-polymerase chain reaction analysis identified cholinergic and fewer
      GABAergic cells to be N/OFQ-responsive. [Nphe(1)]nociceptin-(1-13)-NH(2) and
      CompB (J-113397) antagonized the N/OFQ response, but both compounds also
      displayed partial agonist activity. Using a combination of channel blockers we
      determined that the effects of N/OFQ were mediated via a suite of Ca(2+) (N- and
      L-type) and Ca(2+)-dependent K(+) (iberiotoxin-sensitive) conductances. In
      addition, biophysical analysis of voltage subtraction protocols revealed that
      N/OFQ reduces transient outward and the delayed rectifier K(+) currents. Because
      N-type and L-type Ca(2+) channels are important in the context of
      neurotransmitter release, our observations indicate that N/OFQ inhibition of
      Ca(2+)-dependent conductances in cholinergic neurons would be expected to result
      in depression of acetylcholine release, which may explain the behavioral actions
      of N/OFQ in the brain.

PMID- 12235249
TI  - 5-Hydroxytryptamine(2B) receptor function is enhanced in the N(omega)-nitro-L
      arginine hypertensive rat.
AB  - Arterial hyperresponsiveness to serotonin (5-hydroxytryptamine, 5-HT) is observed
      in experimental models and human forms of hypertension. Presently, we test the
      hypothesis that the 5-HT(2B) receptor is up-regulated and necessary for
      maintaining elevated blood pressure in a rat made hypertensive by the nitric
      oxide synthase inhibitor N(omega)-nitro-L-arginine (LNNA; 0.5 g/l). After 2 weeks
      of treatment, thoracic aorta were removed from LNNA hypertensive (systolic blood
      pressure = 189 +/- 5 mm Hg) and sham normotensive rats (121 +/- 1 mm Hg),
      denuded, and mounted into isolated tissue baths for measurement of isometric
      contraction. In sham tissues, 5-HT-induced contraction was mediated by the 5
      HT(2A) receptor as evidence by a parallel rightward shift in response to 5-HT by
      the 5-HT(2A/2C) receptor antagonist ketanserin (10 nM) and lack of shift by the 5
      HT(2B) receptor antagonist 6-methyl-1,2,3,4-tetrahydro-1-[3,4
      dimethoxyphenyl)methyl]-9H-pyrido[3,4-b]indole hydrochloride (LY272015) (10 nM).
      In contrast, LY272015 produced a 4-fold rightward shift to 5-HT in aorta from
      LNNA hypertensive rats, and blockade by ketanserin did not occur at low
      concentrations of 5-HT. Maximal contraction to the 5-HT(2B) receptor agonist 1-[5
      (2-thienylmethoxy)-1H-3-indolyl]propan-2-amine hydrochloride was significantly
      greater in LNNA hypertensive rats (percentage of phenylephrine contraction in
      sham = 7 +/- 4, and in LNNA = 61 +/- 7%). 5-HT(2B) receptor protein was present
      in aortic homogenates from sham and LNNA rats, but the density of 5-HT(2B)
      receptor protein in LNNA homogenates was 300% that in sham. Importantly, the 5
      HT(2B) receptor antagonist LY272015 reduced blood pressure of the LNNA
      hypertensive but not the sham normotensive rats. Thus, these data suggest that
      the up-regulated 5-HT(2B) receptor in the LNNA hypertensive rats is
      physiologically activated to maintain elevated blood pressure.

PMID- 12235251
TI  - Pharmacological actions of a novel, potent, tissue-selective benzopyran estrogen.
AB  - We have identified a new benzopyran derivative, 3-(4-methoxy) phenyl-4-[[4-[2-(1
      piperidinyl)ethoxy]phenyl]methyl]-2H-1-benzopyran-7-ol hydrochloride (CHF 4227),
      with improved in vivo estrogen agonist/antagonist effects. CHF 4227 binds with
      high affinity to the human estrogen receptor-alpha and -beta (dissociation
      constant K(i) = 0.017 and 0.099 nM, respectively). In immature rats, oral
      administration of CHF 4227 for 3 days inhibited the uterotrophic action of
      17alpha-ethynyl estradiol (EE2) (ED(50) = 0.016 mg/kg. day); raloxifene was 25
      times less potent as estrogen antagonist (ED(50) = 0.39 mg/kg. day), whereas both
      compounds were found to be devoid of uterotrophic activity. In line with its
      estrogen antagonist effect, CHF 4227 significantly prevented the development of
      dimethylbenz[a]anthracene (DMBA)-induced mammary tumors, the incidence being
      reduced from 87.5 to 26.3% 6 months after DMBA administration. In ovariectomized
      (OVX) rats treated orally for 4 weeks, CHF 4227 completely inhibited OVX effects
      on bone density (ED(50) = 0.003 mg/kg. day) and on serum osteocalcin levels. The
      protective effects on bone were comparable with those achieved with EE2, whereas
      raloxifene was less efficacious and 100 times less potent. CHF 4227 reduced serum
      cholesterol (ED(50) = 0.007 mg/kg. day) and had little to no stimulatory effects
      on uterine weight, uterine peroxidase activity, and endometrium epithelial
      thickness. In conclusion, CHF 4227 compares favorably in efficacy and potency
      with raloxifene in preventing bone loss and in antagonizing EE2 stimulation of
      the uterus. This profile along with the minimal uterine stimulation suggests a
      therapeutic advantage to CHF 4227 over EE2 or raloxifene for the treatment of
      postmenopausal women.

PMID- 12235252
TI  - The hypotensive action of rilmenidine is dependent on functional N-methyl-D
      aspartate receptor in the rostral ventrolateral medulla of conscious
      spontaneously hypertensive rats.
AB  - Rilmenidine is a second-generation centrally acting antihypertensive drug that
      acts mainly through the activation of the imidazoline (I(1)) receptor in the
      rostral ventrolateral medulla (RVLM). To investigate the contribution of the N
      methyl-D-aspartate receptor (NMDAR) to the hypotensive action of rilmenidine,
      experiments were undertaken in conscious male spontaneously hypertensive rats
      (SHRs). Microinjection of cumulative doses of rilmenidine (10, 20, and 40 nmol)
      at 10- to 15-min intervals, into the RVLM elicited dose-dependent hypotensive and
      bradycardic response. Pretreatment with intra-RVLM 2-amino-5-phosphonopentanoic
      acid (AP5) (2 nmol), a selective NMDAR antagonist, not only abolished the
      hypotensive response elicited by intra-RVLM rilmenidine (40 nmol) but also
      converted it to a pressor response (-24 +/- 1 versus 17 +/- 7 mm Hg; P < 0.05)
      and significantly attenuated the bradycardic response (-72 +/- 18 versus -24 +/-
      20 bpm; P < 0.05). The blood pressure response to intra-RVLM N-methyl-D-aspartate
      (NMDA) depended on the dose applied. Whereas intra-RVLM NMDA (>20 pmol) produced
      the expected pressor response, a lower dose (10 pmol) reduced mean arterial
      pressure (MAP) (-14 +/- 3 mm Hg) and heart rate (-21 +/- 12 bpm). The divergent
      MAP responses were attenuated by intra-RVLM AP5 (2 nmol), which implicates the
      NMDAR in the pressor as well as the depressor response. The present findings
      suggest that the NMDAR in the RVLM of the SHR 1) exerts dual effects on blood
      pressure, with the response type depending on the level of NMDAR activation, and
      2) plays a pivotal role in the hypotension mediated by I(1) receptor activation
      in the RVLM.

PMID- 12235253
TI  - Reinforcing strength of a novel dopamine transporter ligand: pharmacodynamic and
      pharmacokinetic mechanisms.
AB  - Drugs that block dopamine uptake often function as positive reinforcers but can
      differ along the dimension of strength or effectiveness as a positive reinforcer.
      The present study was designed to examine pharmacological mechanisms that might
      contribute to differences in reinforcing strength between the piperidine-based
      cocaine analog (+)-methyl 4beta-(4-chlorophenyl)-1-methylpiperidine-3-alpha
      carboxylate [(+)-CPCA] and cocaine. Drugs were made available to rhesus monkeys
      (n = 5) for i.v. self-administration under a progressive ratio schedule. Both
      compounds maintained responding with sigmoidal or biphasic dose-response
      functions (0.1-1.0 mg/kg/injection). (+)-CPCA was one-fourth as potent as cocaine
      and maintained fewer injections per session, at maximum. For in vitro binding in
      monkey brain tissue, (+)-CPCA was about one-half as potent as cocaine at the
      dopamine transporter (DAT), and the two compounds had similar affinities at the
      norepinephrine transporter. (+)-CPCA was less than 1/10 as potent as cocaine at
      the serotonin transporter. In ex vivo binding in rat striatum, occupancy of the
      DAT increased directly with dose to a maximum of approximately 80% for both
      compounds, and (+)-CPCA was about one-fourth as potent as cocaine. Ex vivo DAT
      occupancy was significantly higher for cocaine than (+)-CPCA at 2 min after
      injection but similar at other times. Thus, the primary differences between these
      compounds were in serotonin transporter affinity and the kinetics of DAT binding.
      These results suggest that (+)-CPCA is a weaker positive reinforcer than cocaine
      because it has a slower onset of action over the first few minutes after i.v.
      injection.

PMID- 12235254
TI  - Divergent proarrhythmic potential of macrolide antibiotics despite similar QT
      prolongation: fast phase 3 repolarization prevents early afterdepolarizations and
      torsade de pointes.
AB  - Macrolide antibiotics are known to have a different proarrhythmic potential in
      the presence of comparable QT prolongation in the surface ECG. Because the extent
      of QT prolongation has been used as a surrogate marker for cardiotoxicity, we
      aimed to study the different electrophysiological effects of the macrolide
      antibiotics erythromycin, clarithromycin, and azithromycin in a previously
      developed experimental model of proarrhythmia. In 37 Langendorff-perfused rabbit
      hearts, erythromycin (150-300 microM, n = 13) clarithromycin (150-300 microM, n =
      13), and azithromycin (150-300 microM, n = 11) led to similar increases in QT
      interval and monophasic action potential (MAP) duration. In bradycardic
      (atrioventricular-blocked) hearts, eight simultaneously recorded epi- and
      endocardial MAPs demonstrated increased dispersion of repolarization in the
      presence of all three antibiotics. Erythromycin and clarithromycin led to early
      afterdepolarizations (EADs) and torsade de pointes (TdP) after lowering of
      potassium concentration. In the presence of azithromycin, no EAD or TdP occurred.
      Erythromycin and clarithromycin changed the MAP configuration to a triangular
      pattern, whereas azithromycin caused a rectangular pattern of MAP prolongation.
      In 13 additional hearts, 150 microM azithromycin was administered after previous
      treatment with 300 microM erythromycin and suppressed TdP provoked by
      erythromycin. In conclusion, macrolide antibiotics lead to similar prolongation
      of repolarization but show a different proarrhythmic potential (erythromycin >
      clarithromycin > azithromycin). In the presence of azithromycin, neither EAD nor
      TdP occur. This effect may be related to a rectangular pattern of action
      potential prolongation, whereas erythromycin and clarithromycin cause triangular
      action potential prolongation and induce TdP.

PMID- 12235255
TI  - Nonopioid and neuropathy-specific analgesic action of the nootropic drug
      nefiracetam in mice.
AB  - Nootropic drug nefiracetam and related compounds are used in diseases with
      learning and memory deficits. Recent studies have implicated relationships
      between learning, memory, and chronic pain. Thus, in the present report, we have
      studied the effects of nootropic drug nefiracetam on the thermal and mechanical
      hyperalgesia induced by partial sciatic nerve ligation or streptozotocin
      treatment in mice. In the thermal paw withdrawal test, p.o., s.c., i.t., and
      i.c.v. administration of nefiracetam dose dependently reversed the thermal
      hyperalgesia observed in nerve-injured mice. Nefiracetam (p.o. and i.t.) also
      significantly reversed the thermal hyperalgesia observed in streptozotocin
      induced diabetic mice. In the paw pressure test, p.o. and i.t. administration of
      nefiracetam dose dependently reversed the mechanical hyperalgesia observed in
      both nerve-injured and diabetic mice. In contrast, nefiracetam had no effect in
      sham-operated or control nondiabetic mice in all paradigms. Among other
      pyrrolidine nootropics (p.o.), aniracetam produced significant analgesic effects.
      Other analogs also had some, but not significant, analgesic effects. Finally,
      nefiracetam (p.o.)-induced analgesia in injured mice was not affected by opioid
      antagonist naloxone (s.c., i.t., and i.c.v.) but was dose dependently inhibited
      by nicotinic antagonist mecamylamine (i.t. and i.c.v.). The analgesic effect of
      i.t. nefiracetam was also blocked by i.t. mecamylamine pretreatment. Together,
      these findings suggest that nefiracetam, a new member of the piracetam group of
      cognition enhancers, could be a good therapeutic tool against neuropathic pain.
      We also demonstrate that nefiracetam-induced analgesic action was nonopioid in
      nature and was due to stimulation of nicotinic cholinergic system at spinal and
      supraspinal levels.

PMID- 12235256
TI  - Angiotensin-converting enzyme inhibitor-associated angioedema is characterized by
      a slower degradation of des-arginine(9)-bradykinin.
AB  - Angioedema (AE) is a rare but potentially life-threatening side effect of therapy
      with inhibitors of angiotensin-converting enzyme (ACE), the main bradykinin (BK)-
      inactivating metallopeptidase in humans. The pathogenesis of ACE inhibitor (ACEi)
      associated AE (AE+) is presently unknown, although there is increasing evidence
      of a kinin role. We analyzed the metabolism of endogenous BK (B(2) receptor
      agonist) and its active metabolite, des-Arg(9)-BK (B(1) receptor agonist), in the
      presence of an ACEi during in vitro contact activation of plasma from
      hypertensive patients (n = 39) who presented AE+. Kinetic parameters were
      compared with those measured in a control group (AE-) of hypertensive patients (n
      = 39) who never manifested any acute or chronic side effects while treated with
      an ACEi. The different kinetic parameters were analyzed using a mathematical
      model (y = k t(alpha) e(-beta t)) previously applied to a normal, healthy
      population. The slope of BK degradation, but not its formation from high
      molecular-weight kininogen, was lower in AE+ patients when compared with the AE-
      controls. des-Arg(9)-BK accumulation during the kinetic measurements was
      significantly higher in AE+ plasma. This accumulation of the B(1) agonist in AE+
      patients paralleled its half-life of degradation. In conclusion, our results
      show, for the first time, that an abnormality of endogenous des-Arg(9)-BK
      degradation exists in the plasma of patients with ACEi-associated AE, suggesting
      that its pathogenetic mechanism lies in the catabolic site of kinin metabolism.

PMID- 12235257
TI  - Inhibition of epidermal growth factor receptor-mediated signaling by "Combi
      triazene" BJ2000, a new probe for Combi-Targeting postulates.
AB  - The Combi-Targeting concept postulates that a molecule termed combi-molecule (C
      molecule) with binary epidermal growth factor receptor (EGFR) targeting/DNA
      damaging properties and with the ability to be hydrolyzed to another EGFR
      inhibitor should induce sustained antiproliferative activity in cells
      overexpressing EGFR. Because we postulate that the EGFR affinity of the C
      molecule and that of its hydrolytic metabolites are critical parameters for
      sustained potency against EGFR-overexpressing cells, we synthesized BJ2000
      (IC(50) = 0.1 microM, competitive binding at ATP site), a novel C-molecule that
      can decompose into a 6-amino-4-anilinoquinazoline FD105 (IC(50) = 0.2 microM).
      Studies using the EGFR-overexpressing A431 cells revealed that BJ2000 could
      damage DNA and block epidermal growth factor-stimulated EGFR autophosphorylation
      by a partially irreversible mechanism. Blockade of EGFR autophosphorylation
      subsequently induced inhibition of mitogen-activated protein kinase activation
      and c-fos gene expression. Enzyme-linked immunosorbent assay and growth factor
      mediated stimulation of proliferation assays in the EGFR-expressing NIH3T3HER14
      demonstrated the preferential EGFR-targeting properties of BJ2000, and more
      importantly suggest that blockade of EGFR phosphorylation by this drug translate
      into significant growth inhibitory effects. These properties culminated into
      irreversible antiproliferative effects as confirmed by a sulforhodamine B assay.
      Five days after a 2-h treatment, BJ2000 retained significant antiproliferative
      effect in A431 cells, whereas its reversible metabolite FD105 almost completely
      lost its activity. This result in toto lend support to the Combi-Targeting
      concept according to which a molecular conjugate kept small enough to interact
      with EGFR and designed to degrade into another inhibitor of the same target plus
      a DNA-damaging species may induce sustained growth inhibitory effect in EGFR
      overexpressing cells.

PMID- 12235259
TI  - Prenatal opiate withdrawal activates the chick embryo hypothalamic pituitary
      adrenal axis and dilates vitelline blood vessels via serotonin(2) receptors.
AB  - Opiate withdrawal during pregnancy may occur because of voluntary or forced
      detoxification, or from rapid cycling associated with exposure to short-acting
      "street" opiates. Thus, animal modeling of prenatal withdrawal and development of
      potential therapeutic interventions is important. Direct developmental effects of
      opiates and/or withdrawal can be studied using a chick model. In ovo
      administration of the long-acting opiate N-desmethyl-l-alpha-noracetylmethadol
      (NLAAM) induces opiate dependence in the chick embryo. We examined activation of
      the hypothalamic-pituitary-adrenal (HPA) axis (assessed via serum corticosterone)
      and hemodynamic changes (assessed as changes in apparent diameter of vitelline
      (extraembryonic) blood vessels) after chronic NLAAM exposure and naloxone (Nx)
      precipitated withdrawal during late stages of embryogenesis. Nx-precipitated
      withdrawal increased corticosterone 2- to 4.5-fold and diameters of vitelline
      blood vessels by 15 to 45%. NLAAM exposure itself did not effect these measures.
      In a second set of experiments, isobutylmethylxanthine (IBMX), a
      phosphodiesterase inhibitor, was injected into eggs with embryos. IBMX similarly
      increased corticosterone and vitelline vessel diameter, with a similar time
      course and response magnitude. Previous studies found that serotonin(2) (5-HT(2))
      receptors were involved in other withdrawal manifestations, so we determined
      whether they were likewise involved. Pretreatment with the 5-HT(2) antagonist
      ritanserin completely blocked HPA axis activation and vasodilation associated
      with both Nx-precipitated withdrawal and IBMX administration. This indicates that
      5-HT(2) receptors, directly or indirectly, mediate these withdrawal
      manifestations in the chick embryo.

PMID- 12235258
TI  - Tonic inhibitory role for cAMP in alpha(1a)-adrenergic receptor coupling to
      extracellular signal-regulated kinases 1/2.
AB  - alpha(1a)-Adrenergic receptors (ARs) couple to phosphoinositide hydrolysis,
      adenylyl cyclase, and mitogen-activated protein kinase (MAPK) pathways. However,
      the interaction among these signaling pathways in activating extracellular signal
      regulated kinase 1/2 (ERK1/2) is not well understood. We investigated the
      coupling of alpha(1a)-ARs to ERK1/2 in Chinese hamster ovary (CHO)-K1 cells
      stably transfected with mouse alpha(1a)-ARs, as well as the interaction between
      ERK1/2 and norepinephrine-induced cAMP accumulation. alpha(1a)-AR activation by
      norepinephrine increased the cytosolic Ca(2+) concentration and phosphorylated
      ERK1/2 in a time- and concentration-dependent manner. ERK1/2 phosphorylation was
      blocked by the MAPK kinase 1/2 inhibitor 2'-amino-3'-methoxyflavone (PD 98059)
      and the alpha(1)-AR antagonist prazosin. A transient elevation in intracellular
      Ca(2+) was required for the phosphorylation of ERK1/2; however, activation of
      protein kinase C did not seem to be required for ERK1/2 phosphorylation.
      Norepinephrine also stimulated cAMP accumulation in transfected CHO-K1 cells in a
      concentration-dependent manner via alpha(1a)-ARs, which was blocked by the Ca(2+)
      chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Norepinephrine
      induced ERK1/2 phosphorylation was inhibited by the adenylyl cyclase activator
      forskolin and was enhanced by the adenylyl cyclase inhibitor 9-(tetrahydro-2
      furanyl)-9H-purine-6-amine (SQ 22536) and the protein kinase A inhibitor 4-cyano
      3-methylisoquinoline. In conclusion, in transfected CHO-K1 cells, alpha(1a)-AR
      activation activates both phospholipase C and adenylyl cyclase-mediated signaling
      pathways. alpha(1a)-AR-mediated ERK1/2 phosphorylation was dependent on a rise in
      intracellular Ca(2+), and this pathway was reciprocally regulated by the
      concomitant activation of adenylyl cyclase, which inhibits ERK1/2
      phosphorylation. Thus, alpha(1a)-AR stimulation of cAMP production may play an
      important role in regulating ERK1/2 phosphorylation in cell lines and native
      tissues.

PMID- 12235260
TI  - Dual mechanisms for ethanol-induced inhibition of monocyte chemotactic protein-3
      mRNA expression in activated glial cells.
AB  - The differential display of mRNA technique was used to screen the expressed genes
      in control and 50 mM chronic ethanol-treated rat C6 glial cells, with and without
      activation by lipopolysaccharide (LPS) combined with phorbol 12-myristate 13
      acetate (PMA). One differentially expressed transcript was identified as that
      corresponding to the chemokine monocyte chemotactic protein (MCP)-3. MCP-3 is a
      broadly active chemokine that functions in chemoattraction and activation of
      monocytes, T lymphocytes, eosinophils, basophils, natural killer cells, and
      dendritic cells. Steady-state MCP-3 mRNA levels were elevated 6-fold after 24-h
      stimulation of control cells but less than 3-fold after stimulation of 9-day
      chronic ethanol-exposed cells. One- and 5-day exposures to 50 mM ethanol were not
      effective at reducing steady-state MCP-3 mRNA levels in stimulated cells, whereas
      1-day exposure to >150 mM ethanol was effective. Stimulation with tumor necrosis
      factor-alpha elevated MCP-3 mRNA in C6 glial cells to a lesser extent than with
      LPS plus PMA, but the effects of ethanol were consistent. To gain insight into
      possible mechanisms for ethanol-induced reductions in steady-state MCP-3 mRNA,
      additional studies examined nuclear MCP-3 RNA levels and MCP-3 mRNA degradation.
      MCP-3 RNA content was greatly reduced in isolated nuclei from acute and chronic
      ethanol-exposed cells, suggesting transcriptional inhibition. On the other hand,
      acute ethanol exposure enhanced degradation of preexisting MCP-3 mRNA, indicating
      message destabilization. Thus, the results are consistent with a dual mechanism
      for ethanol-induced reductions in steady-state MCP-3 mRNA levels.

PMID- 12235261
TI  - Inflammatory cytokines, but not bile acids, regulate expression of murine hepatic
      anion transporters in endotoxemia.
AB  - Endotoxin-mediated cholestasis stems from impaired hepatobiliary transport of
      bile acids and organic anions due to altered expression and activity of
      transporters, including Oatp, Mrp, Ntcp, and Bsep. However, the mechanisms by
      which the Oatp and Mrp genes are down-regulated are largely unknown. Using in
      vivo and in vitro murine models of inflammation, we examined the role of
      cytokines and bile acids in regulating Oatp and Mrp. Endotoxin
      (lipopolysaccharide, LPS), interleukin (IL)-6, IL-1beta, tumor necrosis factor
      (TNF)-alpha, cholic acid, taurocholate, or taurodeoxycholate was administered in
      vivo to mice or in vitro to Hepa 1-6 mouse hepatoma cells. Mrp, Oatp, and Bsep
      mRNA levels were measured by reverse transcription-polymerase chain reaction. Mrp
      efflux activity was measured using 5-carboxyfluorescein. In vivo, LPS treatment
      profoundly suppressed hepatic mRNA levels of Mrp2, Mrp3, Oatp1, Oatp2, and Bsep
      to 15, 60, 44, 30, and 32% of controls, respectively (p < 0.05), but did not
      significantly alter Mrp1 expression. IL-6 or IL-1beta administration suppressed
      Mrp2, Oatp1, Oatp2, and Bsep mRNA levels to 20 to 60% controls (p < 0.05). TNF
      alpha administration affected mRNA levels of Mrp2, Mrp3, and Oatp2 but not Oatp1
      or Bsep. Bile acid treatment increased the in vivo expression of Bsep but not Mrp
      or Oatp. Likewise, significantly lower mRNA levels of Mrp2 with a corresponding
      decrease in cellular efflux of 5-carboxyfluorescein was seen in vitro in IL-6-
      and IL-1beta-treated Hepa 1-6 cells, whereas bile acids did not have significant
      effects. In conclusion, cytokines are key mediators in regulating hepatic
      expression of anion transporters in inflammatory cholestasis, whereas bile acids
      likely play a minor role.

PMID- 12235262
TI  - Inhibitory effects of the antiestrogen agent clomiphene on cardiac sarcolemmal
      anionic and cationic currents.
AB  - The aim of this study was to determine the effects of the antiestrogen agent
      clomiphene on cardiac anionic and cationic sarcolemmal ion channels. Whole-cell
      recordings were made from rat and guinea pig ventricular myocytes. Clomiphene
      inhibited the volume-regulated chloride current [I(Cl,vol), activated by cell
      swelling after hypotonic shock (approximately 145 mOsM)] with an IC(50) value of
      approximately 9.4 microM. In contrast, at concentrations up to 100 microM,
      clomiphene failed to inhibit both the chloride current activated by cyclic AMP
      (I(Cl,cAMP)) and the anionic background current (I(AB)). At 10 microM, clomiphene
      blocked the voltage-gated fast sodium current and the L-type calcium current
      (I(Ca,L)) in both species. The voltage-independent fractional block of I(Ca,L)
      induced by clomiphene (10 microM) was approximately 82%, this concentration also
      inhibited the inwardly rectifying K(+) current with a fractional current block of
      approximately 26% at -90 mV. Fractional block of outward current at +70 mV in rat
      was approximately 25%, implying that delayed rectifying K(+) channels were also
      affected by clomiphene. We conclude that clomiphene shows selectivity for
      I(Cl,vol) over I(Cl,cAMP) and I(AB) and therefore represents a useful tool for
      studying chloride conductances in isolated ventricular myocytes with interfering
      currents blocked. However, due to its effects on cation conductances it would be
      of little value in this regard for other types of in vitro or in vivo
      experiments.

PMID- 12235263
TI  - 1-[4-[4[(4R,5R)-3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1
      dioxido-1-benzothiepin-5-yl]phenoxy]butyl]-4-aza-1-azoniabicyclo[2.2.2]octane
      methanesulfonate (SC-435), an ileal apical sodium-codependent bile acid
      transporter inhibitor alters hepatic cholesterol metabolism and lowers plasma low
      density lipoprotein-cholesterol concentrations in guinea pigs.
AB  - Male Hartley guinea pigs (10/group) were assigned either to a control diet (no
      drug treatment) or to diets containing 0.4, 2.2, or 7.3 mg/day of an ileal apical
      sodium-codependent bile acid transporter (ASBT) inhibitor, 1-[4-[4[(4R,5R)-3,3
      dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin
      5-yl]phenoxy]butyl]-4-aza-1-azoniabicyclo[2.2.2] octane methanesulfonate (SC
      435). Based on food consumption, guinea pigs received 0, 0.8, 3.7, or 13.4
      mg/kg/day of the ASBT inhibitor. The amount of cholesterol in the four diets was
      maintained at 0.17%, equivalent to 1200 mg/day in the human situation. Guinea
      pigs treated with 13.4 mg/kg/day SC-435 had 41% lower total cholesterol and 44%
      lower low-density lipoprotein (LDL)-cholesterol concentrations compared with
      control (P < 0.01), whereas no significant differences were observed with either
      of the lower doses of SC-435. Hepatic cholesterol esters were significantly
      reduced by 43, 56, and 70% in guinea pigs fed 0.8, 3.7, and 13.4 mg/kg/day of the
      ASBT inhibitor, respectively (P < 0.01). In addition, the highest dose of the
      inhibitor resulted in a 42% increase in the number of very low-density
      lipoprotein (VLDL) triacylglycerol molecules and a larger VLDL diameter compared
      with controls (P < 0.05). Acyl-CoA cholesterol/acyltransferase activity was 30%
      lower with the highest dose treatment, whereas cholesterol 7alpha-hydroxylase,
      the regulatory enzyme of bile acid synthesis, was 30% higher with the highest
      ASBT inhibitor dose (P < 0.05). Furthermore, bile acid excretion increased 2-fold
      with the highest dose of SC-435 compared with the control group (P < 0.05). These
      results suggest that the reduction in total and LDL-cholesterol concentrations by
      the ASBT inhibitor is a result of alterations in hepatic cholesterol metabolism
      due to modifications in the enterohepatic circulation of bile acids.

PMID- 12235264
TI  - Histamine h(4) and h(2) receptors control histamine-induced interleukin-16
      release from human CD8(+) T cells.
AB  - Histamine is known to trigger the release of interleukin (IL)-16 from human
      CD8(+) cells. However, the individual roles of the presently known histamine
      receptor subtypes (H(1)-H(4)) in this inflammatory response have not been fully
      characterized. Histamine stimulation of human CD8(+) T lymphocytes purified from
      peripheral blood led to a 5- to 8-fold increase in the basal release of IL-16
      within 24 h, and this increase was significantly blocked by the H(2)-selective
      antagonist, cimetidine, or by thioperamide, an antagonist of H(3) and H(4)
      receptors, respectively. The H(1) antagonist pyrilamine showed limited effects.
      Agonists selective for H(2) (dimaprit), H(3/4) (R-(-)-alpha-methylhistamine), and
      H(4) (clobenpropit) were capable of inducing the release of bioactive IL-16
      because CD8(+) cell supernatants induced CD4(+) cell migration, which was
      abrogated by an anti-IL-16 antibody. Furthermore, preincubation of lymphocytes
      with pertussis toxin abolished IL-16 release triggered by activation of the
      G(i/o)-coupled H(4) receptor but not by the H(2) receptor. Messenger RNA
      expression studies confirmed H(4), H(2), and H(1) expression in human CD8(+)
      lymphocytes, whereas H(3) mRNA was completely absent. All leukocyte populations
      investigated expressed mRNA for H(4), with highest levels found in eosinophils,
      dendritic cells, and tonsil B cells. H(4) expression was also detected in human
      lung, trachea, and various cells of human lung origin, such as fibroblasts,
      bronchial smooth muscle cells, epithelial, and endothelial cells. Since many of
      those are known sources of IL-16, immune cell- and lung cell-expressed H(4)
      receptors may have a general role in the control of this mediator of inflammatory
      disorders such as asthma.

PMID- 12235265
TI  - Sirolimus oral absorption in rats is increased by ketoconazole but is not
      affected by D-alpha-tocopheryl poly(ethylene glycol 1000) succinate.
AB  - The contributions of cytochrome P450 3A (CYP3A) and P-glycoprotein to sirolimus
      oral bioavailability in rats were evaluated by coadministration of sirolimus
      (Rapamune) with the CYP3A inhibitor ketoconazole or the P-glycoprotein inhibitor
      D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS). Groups of six
      male Sprague-Dawley rats (250-300 g) were administered Rapamune (1 mg/kg) by oral
      gavage, alone and with ketoconazole (30 mg/kg) or TPGS (50 mg/kg). Sirolimus
      levels were measured in whole blood over a 6-h time course. Sirolimus C(max) (6.6
      +/- 1.6 versus 26 +/- 7 ng/ml) and area under the concentration versus time curve
      from 0 to 6 h (AUC(0-6)) (22 +/- 7 versus 105 +/- 27 ng. h/ml) were increased 3-
      to 5-fold by ketoconazole. Median T(max) (1.5-2 h) was unchanged. TPGS had no
      effect on sirolimus absorption. The interaction of sirolimus with P-glycoprotein
      was also evaluated in vitro using HCT-8 and Caco-2 cell monolayers. Consistent
      with published reports, sirolimus was a good inhibitor of P-glycoprotein,
      inhibiting polarized basolateral-to-apical flux of rhodamine 123 with an IC(50)
      of 0.625 to 1.25 microM (cyclosporine caused >80% inhibition at 5 microM).
      Sirolimus did not demonstrate significant polarized flux in either direction
      using the same monolayers (basolateral-to-apical flux was <2 times the apical-to
      basolateral). Moreover, sirolimus flux was not impacted by cyclosporine,
      suggesting that it does not undergo P-glycoprotein-mediated transport in this
      system. The lack of significant sirolimus transport by P-glycoprotein may, in
      part, explain the lack of a TPGS effect on sirolimus absorption in rats.

PMID- 12235266
TI  - Inhibition of improgan antinociception by the cannabinoid (CB)(1) antagonist N
      (piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3
      carboxamide (SR141716A): lack of obligatory role for endocannabinoids acting at
      CB(1) receptors.
AB  - Improgan, a nonopioid antinociceptive agent, activates descending, pain-relieving
      mechanisms in the brain stem, but the receptor for this compound has not been
      identified. Because cannabinoids also activate nonopioid analgesia by a brain
      stem action, experiments were performed to assess the significance of cannabinoid
      mechanisms in improgan antinociception. The cannabinoid CB(1) antagonist N
      (piperidin-1-yl)-5-(4-chloro phenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole
      3-carboxamide (SR141716A) induced dose-dependent inhibition of improgan
      antinociception on the tail-flick test after i.c.v. administration in rats. The
      same treatments yielded comparable inhibition of cannabinoid [R-(+)-(2,3-dihydro
      5-methyl-3-[(4-mor pholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazin-6-yl)(1
      naphthalenyl)methanone monomethanesulfonate, WIN 55,212-2] analgesia. Inhibition
      of improgan and WIN 55,212-2 antinociception by SR141716A was also observed in
      Swiss-Webster mice. Radioligand binding studies showed no appreciable affinity of
      improgan on rat brain, mouse brain, and human recombinant CB(1) receptors, ruling
      out a direct action at these sites. To test the hypothesis that CB(1) receptors
      indirectly participate in improgan signaling, the effects of improgan were
      assessed in mice with a null mutation of the CB(1) gene with and without
      SR141716A pretreatment. Surprisingly, improgan induced complete antinociception
      in both CB(1) (-/-) and wild-type control [CB(1) (+/+)] mice. Furthermore,
      SR141716A inhibited improgan antinociception in CB(1) (+/+) mice, but not in
      CB(1) (-/-) mice. Taken together, the results show that SR141716A reduces
      improgan antinociception, but neither cannabinoids nor CB(1) receptors seem to
      play an obligatory role in improgan signaling. Present and previous studies
      suggest that Delta(9)-tetrahydrocannabinol may act at both CB(1) and other
      receptors to relieve pain, but no evidence was found indicating that improgan
      uses either of these mechanisms. SR141716A will facilitate the study of improgan
      like analgesics.

PMID- 12235268
TI  - Cross-talk between AT(1) and AT(2) angiotensin receptors in rat anococcygeus
      smooth muscle.
AB  - Schild regressions for the selective AT(1) and AT(2) receptor antagonists,
      losartan and PD123319 (S-[+]-1-[(4-dimethylamino]-3-methylphenyl)methyl]-5
      [diphenylacetyl]-4,5,6,7-tetrahydro-1H-imidazol[4,5-c]pyridine-6-carboxilic
      acid), respectively, were calculated to analyze the heterogeneity of receptor
      populations in the rat anococcygeus muscle. For a one-receptor system, the Schild
      regression has a slope of unity and an intercept of K(B) for competitive
      antagonists. However, in a two-receptor system, a deviation from the single
      receptor plot will occur. This is predicated on the assumption that the secondary
      receptor is less sensitive to the antagonist than the primary receptor. Results
      showed that the Schild regression for losartan did not produce a slope of unity,
      and PD123319 did not produce any effect. However, tissue incubation with losartan
      plus PD123319 resulted in a Schild regression that has a slope of unity and a
      pK(B) of 9.32. In the presence of prazosin, an alpha(1)-adrenoceptor antagonist,
      losartan did not produce any effect. Conversely, PD123319 enhanced the
      angiotensin II (Ang II)-induced contraction in a concentration-dependent fashion,
      suggesting an inhibitory AT(2)-mediated effect. This effect was confirmed with
      assays that showed a relaxant response induced by Ang II on precontracted tissues
      incubated with prazosin. PD123319 and N(G)-nitro-L-arginine methyl ester [nitric
      oxide (NO) synthase inhibitor)] markedly inhibited the relaxant response of Ang
      II. In contrast, losartan did not produce any significant effect. Consequently,
      results show that the mechanism underlying the AT(2)-mediated effect is highly
      dependent on NO generation. Results indicate the presence of a heterogeneous
      angiotensin receptor population in the rat anococcygeus muscle following a
      negative cross-talk relationship between the AT(1) and AT(2) subtypes.

PMID- 12235267
TI  - Interaction of cytochrome P450 3A inhibitors with P-glycoprotein.
AB  - Many clinically important drug interactions occur due to inhibition of human
      liver cytochrome P450 3A (CYP3A) metabolism. The drug efflux pump P-glycoprotein
      (Pgp) can be an additional locus contributing to these drug interactions because
      there is overlap in drugs that are substrates for both proteins. We screened a
      number of CYP3A inhibitors (macrolide antibiotics, azole antifungals, and
      ergotpeptides) for their ability to interact with Pgp, compared with prototypical
      Pgp inhibitors. We used cell lines expressing human, mouse, and rat mdr1 genes.
      Pgp antagonism was defined by interactions of the drugs with four cell lines (LLC
      PK1, L-MDR1, L-mdr1a, and L-mdr1b) using a microfluorometric calcein-AM assay and
      characterized for their inhibitor constant (K(i)) toward calcein-AM. The
      compounds were further defined for their ability to inhibit MDR1 by their effect
      on vinblastine accumulation into L-MDR1 cells. Representative compounds from each
      class of drugs were further tested as Pgp substrates, defined by the ability of
      human Pgp or mouse mdr1a/Pgp to transport them across a polarized kidney
      epithelial cell in vitro. These same compounds were administered radiolabeled in
      vivo to mdr1a (+/+) and (-/-) mice and the distribution of radioactivity
      compared. The results are summarized as follows: 1) Some drug interactions with
      Pgp were substrate- and/or assay-dependent. 2) Ergot alkaloids were identified as
      a class of MDR1/Pgp chemosensitizers. 3) The Ergot alkaloids revealed species
      differences in the structure-activity relationships for inhibition of Pgp.
      Simultaneous inhibition of Pgp by many CYP3A inhibitors contributes to human
      variation in the extent of drug-drug interactions.

PMID- 12235269
TI  - Decrease in efficacy and potency of nonsteroidal anti-inflammatory drugs by
      chronic delta(9)-tetrahydrocannabinol administration.
AB  - Cannabinoids have been shown to increase the release of arachadonic acid, whereas
      nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to decrease the
      analgesic effects of cannabinoids. We evaluated the antinociceptive effects of
      chronic administration of Delta(9)-tetrahydrocannabinol (Delta(9)-THC),
      anandamide (an endogenous cannabinoid), arachadonic acid, ethanolamine, and
      methanandamide on several NSAIDs via p.o. and/or i.p. routes of administration
      using the mouse p-phenylquinone (PPQ) test, a test for visceral nociception. Our
      studies with a cannabinoid receptor (CB1) antagonist [N-(piperidin-1-yl)-5-(4
      chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide
      hydrochloride (SR141716A)], a CB2 antagonist [N-((1S)-endo-1,3,3-trimethyl
      bicyclo-heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3
      carboxamide) (SR144528)], and an another CB2 agonist [1,1-dimethylbutyl-1-deoxy
      Delta(9)-THC (JWH-133)] were performed to better characterize PPQ interactions
      with cannabinoid receptors. The acute affects of Delta(9)-THC were blocked by
      SR141716A (i.p.) and partially blocked by SR144528 (i.p.). When NSAIDs (p.o.)
      were administered, the ED(50) values were as follows: 23 mg/kg aspirin, 3 mg/kg
      indomethacin, 5 mg/kg celecoxib, 3 mg/kg ketorolac, 57 mg/kg acetaminophen (32.3
      99.8), and 0.8 mg/kg diclofenac (0.1-4.9). In animals given chronic Delta(9)-THC,
      only diclofenac and acetaminophen were active. Conversely, chronic methanandamide
      (i.p.) did not alter the antinociceptive effects of the NSAIDs. Neither the CB1
      or CB2 antagonist blocked the effects of the NSAIDs. The effects of chronic
      arachadonic acid, ethanolamine, and anandamide could not be evaluated. In
      summary, our data indicate that chronic Delta(9)-THC alters the cyclooxygenase
      system. Alternatively, the data suggest that this alteration is not due to
      chronic endogenous cannabinoid release. Based upon these data, we hypothesize
      that human subjects who are chronic users of Delta(9)-THC may not respond to
      analgesic treatment with the above NSAIDs.

PMID- 12235270
TI  - Differential effects of linoleic Acid metabolites on cardiac sodium current.
AB  - 9,10-Epoxy-12-octadecenoic acid (EOA), a metabolite of linoleic acid, causes
      cardiac arrest in dogs. Other metabolites of linoleic acid also have toxic
      effects. This study investigates the mechanism of action of four of these
      compounds on cardiac Na(+) current (I(Na)). The whole-cell patch-clamp technique
      was used to investigate the effects of EOA, 9,10-dihydroxy-12-octadecenoic acid
      (DHOA), and their corresponding methyl esters (9,10-epoxy-12-octadecenoic methyl
      ester, EOM; and 9,10-dihydroxy-12-octadecenoic methyl ester, DHOM) on I(Na) in
      isolated adult rat ventricular myocytes. Extracellular application of each
      compound elicited a concentration-dependent inhibition of I(Na). The dose
      response curve yielded 50% inhibition concentrations of 301 +/- 117 microM for
      DHOA, 41 +/- 6 microM for DHOM, 34 +/- 5 microM for EOA, and 160 +/- 41 microM
      for EOM. Although there was no effect on activation, 50 microM DHOM, EOA, and EOM
      significantly hyperpolarized the steady-state inactivation curve by approximately
      -6 mV. Furthermore, EOM significantly increased the slope of the steady-state
      inactivation curve. These compounds also seemed to stabilize the inactivated
      state because the time for recovery from inactivation was significantly slowed
      from a control value of 12.9 +/- 0.5 ms to 30.5 +/- 3.3, 31.4 +/- 1.4, and 20.5
      +/- 1.0 ms by 50 microM DHOM, EOA, and EOM, respectively. These compounds have
      multiple actions on Na(+) channels and that despite their structural similarities
      their actions differ from each other. The steady-state block of I(Na) suggests
      that either the pore is being blocked or the channels are prevented from gating
      to the open state. In addition, these compounds stabilize the inactivated state
      and promote increased population of a slower inactivated state.

PMID- 12235271
TI  - Modulation of hippocampal glutamatergic transmission by ATP is dependent on
      adenosine a(1) receptors.
AB  - Excitatory glutamatergic synapses in the hippocampal CA1 region of rats are
      potently inhibited by purines, including adenosine, ATP, and ATP analogs.
      Adenosine A(1) receptors are known to mediate at least part of the response to
      adenine nucleotides, either because adenine nucleotides activate A(1) receptors
      directly, or activate them secondarily upon the nucleotides' conversion to
      adenosine. In the present studies, the inhibitory effects of adenosine, ATP, the
      purportedly stable ATP analog adenosine-5'-O-(3-thio)triphosphate (ATPgammaS),
      and cyclic AMP were examined in mice with a null mutation in the adenosine A(1)
      receptor gene. ATPgammaS displaced the binding of A(1)-selective ligands to
      intact brain sections and brain homogenates from adenosine A(1) receptor wild
      type animals. In homogenates, but not in intact brain sections, this displacement
      was abolished by adenosine deaminase. In hippocampal slices from wild-type mice,
      purines abolished synaptic responses, but slices from mice lacking functional
      A(1) receptors showed no synaptic modulation by adenosine, ATP, cAMP, or
      ATPgammaS. In slices from heterozygous mice the dose-response curve for both
      adenosine and ATP was shifted to the right. In all cases, inhibition of synaptic
      responses by purines could be blocked by prior treatment with the competitive
      adenosine A(1) receptor antagonist 8-cyclopentyltheophylline. Taken together,
      these results show that even supposedly stable adenine nucleotides are rapidly
      converted to adenosine at sites close to the A(1) receptor, and that inhibition
      of synaptic transmission by purine nucleotides is mediated exclusively by A(1)
      receptors.

PMID- 12235272
TI  - Lipopolysaccharide-induced acute renal failure in conscious rats: effects of
      specific phosphodiesterase type 3 and 4 inhibition.
AB  - In conscious, chronically instrumented rats we examined 1) renal tubular
      functional changes involved in lipopolysaccharide (LPS)-induced acute renal
      failure; 2) the effects of LPS on the expression of selected renal tubular water
      and sodium transporters; and 3) effects of milrinone, a phosphodiesterase type 3
      (PDE3) inhibitor, and Ro-20-1724, a PDE4 inhibitor, on LPS-induced changes in
      renal function. Intravenous infusion of LPS (4 mg/kg b.wt. over 1 h) caused an
      immediate decrease in glomerular filtration rate (GFR) and proximal tubular
      outflow without changes in mean arterial pressure (MAP). LPS-induced fall in GFR
      and proximal tubular outflow were sustained on day 2. Furthermore, LPS-treated
      rats showed a marked increase in fractional distal water excretion, despite
      significantly elevated levels of plasma vasopressin (AVP). Semiquantitative
      immunoblotting showed that LPS increased the expression of the Na(+),K(+),2Cl(-)
      cotransporter (BSC1) in the thick ascending limb, whereas the expression of the
      AVP-regulated water channel aquaporin-2 in the collecting duct (CD) was
      unchanged. Pretreatment with milrinone or Ro-20-1724 enhanced LPS-induced
      increases in plasma tumor necrosis factor-alpha and lactate, inhibited the LPS
      induced tachycardia, and exacerbated the acute LPS-induced fall in GFR.
      Furthermore, Ro-20-1724-treated rats were unable to maintain MAP. We conclude 1)
      PDE3 or PDE4 inhibition exacerbates LPS-induced renal failure in conscious rats;
      and 2) LPS treated rats develop an escape from AVP in the CDs, which could be
      aimed to protect against water intoxication in septic conditions associated with
      decreased GFR and high levels of AVP.

PMID- 12235273
TI  - Role of the nitric oxide pathway in kappa-opioid-induced hypothermia in rats.
AB  - The effect of central and peripheral administration of a nitric oxide synthase
      inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on the hypothermia induced
      by the selective kappa-opioid receptor agonist trans-(+/-)3,4-dichloro-N-methyl-N
      (2-[1-pyrrolidinyl]-cyclohexyl)-benzeneacetamide methane sulfate (U50,488H) was
      studied in male Sprague-Dawley rats. In the first series of experiments, we
      examined the effect of subcutaneous (s.c.) administration of L-NAME on the
      hypothermia induced by s.c. injection of U50,488H. L-NAME, at a dose of 50 mg/kg
      s.c., had no influence on body temperature (Tb). Coadministration of L-NAME (50
      mg/kg, s.c.) with U50,488H (10 mg/kg, s.c.) blocked the hypothermia induced by
      U50,488H. In the second series of experiments, we investigated the effect of
      intracerebroventricular (i.c.v.) administration of L-NAME on the hypothermia
      induced by s.c. injection of U50,488H. L-NAME itself, given i.c.v. at a dose of 1
      mg/rat, did not evoke any change in Tb. Administration of L-NAME (1 mg/rat,
      i.c.v.) caused a significant suppression of U50,488H hypothermia. The results
      indicate that either central or peripheral nitric oxide synthesis is required for
      the production of hypothermia induced by U50,488H.

PMID- 12235274
TI  - (-)-(9S)-9-(3-Bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin
      8(4H)-one 1,1-dioxide (A-278637): a novel ATP-sensitive potassium channel opener
      efficacious in suppressing urinary bladder contractions. I. In vitro
      characterization.
AB  - Alterations in the myogenic activity of the bladder smooth muscle are thought to
      serve as a basis for the involuntary detrusor contractions associated with the
      overactive bladder. Activation of ATP-sensitive K(+) (K(ATP)) channels has been
      recognized as a potentially viable mechanism to modulate membrane excitability in
      bladder smooth muscle. In this study, we describe the preclinical pharmacology of
      (-)-(9S)-9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin
      8(4H)-one 1,1-dioxide (A-278637), a novel 1,4-dihydropyridine K(ATP) channel
      opener (KCO) that demonstrates enhanced bladder selectivity for the suppression
      of unstable bladder contractions in vivo relative to other reference KCOs. A
      278637 activated K(ATP) channels in bladder smooth muscle cells in a glyburide
      (glibenclamide)-sensitive manner as assessed by fluorescence membrane potential
      assays using bis-(1,3-dibutylbarbituric acid)trimethine oxonol (EC(50) = 102 nM)
      and by whole cell patch clamp. Spontaneous (myogenic) phasic activity of pig
      bladder strips was suppressed (IC(50) = 23 nM) in a glyburide-sensitive manner by
      A-278637. A-278637 also inhibited carbachol- and electrical field-stimulated
      contractions of bladder strips, although the respective potencies were 8- and 13
      fold lower compared with inhibition of spontaneous phasic activity. As shown in
      the accompanying article [Brune ME, Fey TA, Brioni JD, Sullivan JP, Williams M,
      Carroll WA, Coghlan MJ, and Gopalakrishnan M (2002) J Pharmacol Exp Ther 303:387
      394], A-278637 suppressed myogenic contractions in vivo in a model of bladder
      instability with superior selectivity compared with other KCOs, WAY-133537 [(R)-4
      [3,4-dioxo-2-(1,2,2-trimethyl-propylamino)cyclobut-1-enylamino]-3-ethyl
      benzonitrile] and ZD6169 [(S)-N-(4-benzoylphenyl)3,3,3-trifluro-2hydroxy-2-methyl
      priopionamide]. A-278637 did not interact with other ion channels, including L
      type calcium channels or other neurotransmitter receptor systems. The
      pharmacological profile of A-278637 represents an attractive basis for further
      investigations of selective K(ATP) channel openers for the treatment of
      overactive bladder via myogenic etiology.

PMID- 12235275
TI  - (-)-(9S)-9-(3-Bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin
      8(4H)-one 1,1-dioxide (A-278637): a novel ATP-sensitive potassium channel opener
      efficacious in suppressing urinary bladder contractions. II. in vivo
      characterization.
AB  - ATP-sensitive potassium (K(ATP)) channel openers (KCOs) have been shown to
      inhibit spontaneous myogenic contractile activity of the urinary bladder, a
      mechanism hypothesized to underlie detrusor instability and symptoms of
      overactive bladder. However, the therapeutic utility of KCOs has been limited by
      a lack of differentiation of bladder versus vascular effects. In this study, we
      evaluated the in vivo potency and bladder selectivity of (-)-(9S)-9-(3-bromo-4
      fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A
      278637), a novel dihydropyridine KCO, in a pig model of detrusor instability
      secondary to partial bladder outlet obstruction. For comparison, we profiled two
      KCOs, ((R)-4-[3,4-dioxo-2-(1,2,2-trimethyl-propylamino)-cyclobut-1-enylamino]-3
      ethyl-benzonitrile (WAY-133537) and (S)-N-(4-benzoylphenyl)-3,3,3-trifluro-2
      hydroxy-2-methyl-propionamide (ZD6169), reported previously to have improved
      bladder selectivity in vivo and a calcium channel blocker, nifedipine. Effective
      doses of A-278637, WAY-133537, ZD6169, and nifedipine to inhibit unstable
      contraction area under the curve by 35% and to decrease mean arterial pressure by
      10% were 4.2 and 12, 109 and 51, 661 and 371, and 136 and 30 nmol/kg i.v.,
      yielding corresponding bladder selectivity ratios of 3, 0.5, 0.6, and 0.2.
      Therefore, A-278637 was approximately 5- to 6-fold more bladder-selective than
      the other KCOs and 15-fold more selective than nifedipine, the latter
      approximately 4.5-fold vascular-selective. The potency of KCOs to inhibit
      unstable contraction in vivo was accurately predicted by their potency to inhibit
      spontaneous contractile activity of pig detrusor strips in vitro. These results
      indicate that A-278637, with enhanced potency and bladder selectivity compared
      with the other compounds evaluated, could serve as a useful tool in the
      investigation of smooth muscle K(ATP) channel openers as novel therapeutic agents
      for the treatment of overactive bladder.

PMID- 12235276
TI  - N-methyl-D-aspartate antagonists and WIN 55212-2 [4,5-dihydro-2-methyl-4(4
      morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1-i,j]quinolin-6
      one], a cannabinoid agonist, interact to produce synergistic hypothermia.
AB  - CB(1) cannabinoid receptors mediate profound hypothermia when cannabinoid
      agonists are administered to rats. Glutamate, the principal excitatory
      neurotransmitter in the central nervous system (CNS), is thought to tonically
      increase body temperature by activating N-methyl-D-aspartate (NMDA) receptors.
      Because NMDA antagonists block cannabinoid-induced antinociception and catalepsy,
      intimate glutamatergic-cannabinoid interactions may exist in the CNS. The present
      study investigated the effect of two NMDA antagonists on the hypothermic response
      to WIN 55212-2 [4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl
      carbonyl)-6H-pyrrolo[3,2,1-i,j]quinolin-6-one], a selective cannabinoid agonist,
      in rats. WIN 55212-2 (1-10 mg/kg i.m.) produced dose-dependent hypothermia that
      peaked 60 to 180 min postinjection. Dextromethorphan (5-75 mg/kg i.m.), a
      noncompetitive NMDA antagonist, or LY 235959 [(-)-6-[phosphonomethyl
      1,2,3,4,4a,5,6,7,8,8a-decahydro-isoquinoline-2-carboxylate]](1-4 mg/kg i.m.), a
      competitive and highly selective NMDA antagonist, evoked hypothermia in a dose
      sensitive manner, suggesting that endogenous glutamate exerts a hyperthermic tone
      on body temperature. A dose of dextromethorphan (10 mg/kg) that did not affect
      body temperature by itself potentiated the hypothermic response to WIN 55212-2
      (1, 2.5, or 5 mg/kg). The enhancement was strongly synergistic, indicated by a
      2.7-fold increase in the relative potency of WIN 55212-2. Similarly, a dose of LY
      235959 (1 mg/kg) that did not affect body temperature augmented the hypothermia
      associated with a single dose of WIN 55212-2 (2.5 mg/kg), thus confirming that
      NMDA receptors mediated the synergy. We have demonstrated previously that CB(1)
      receptors mediate WIN 55212-2-evoked hypothermia in rats. The present data are
      the first evidence that NMDA antagonists exert a potentiating effect on
      cannabinoid-induced hypothermia. Taken together, these data suggest that
      interactions between NMDA and CB(1) receptors produce synergistic hypothermia.

PMID- 12235277
TI  - Relationship between alpha(1)-adrenergic receptor-induced contraction and
      extracellular signal-regulated kinase activation in the bovine inferior alveolar
      artery.
AB  - The endogenous adrenergic agonists norepinephrine (NE) and epinephrine regulate
      vascular tone by stimulating alpha(1)-adrenergic receptors (ARs) on smooth muscle
      cells to cause contraction. In addition, alpha(1)-ARs also couple to growth
      factor pathways, through stimulation of mitogen-activated protein kinases
      (MAPKs). MAPKs are a family of serine-threonine kinases that include
      extracellular signal-regulated kinase (ERK) and a variety of other kinases that
      are able to activate transcription factors when stimulated. We examined alpha(1)
      AR stimulation of contraction and ERK activation in the bovine inferior alveolar
      artery (BIAA), using in vitro contraction studies and Western blotting. Using
      antagonists selective for individual adrenergic receptor types, we found that
      only alpha(1)-ARs were coupled to ERK activation and contraction. NE stimulated
      contraction (EC(50) = 11 microM) and ERK activation (EC(50) = 21 microM) with
      similar potency. Using alpha(1)-AR subtype-selective antagonists, we identified
      the alpha(1)-AR subtypes coupled to each response. Affinity values for alpha(1)
      AR subtype-selective antagonists were consistent with alpha(1A)-AR-mediated
      contraction. In contrast, simultaneous treatment with concentrations of these
      antagonists selective for each alpha(1)-AR subtype (alpha(1A)-, alpha(1B)-, and
      alpha(1D)-AR) was required to inhibit ERK activation, suggesting that all three
      alpha(1)-ARs activate ERK in BIAA. Transmural electrical stimulation of BIAA
      segments resulted in activation of ERK, which was inhibited by the alpha(1)-AR
      selective antagonist BE 2254 (2-[[beta-(4-hydroxyphenyl)ethyl]aminomethyl]-1
      tetralone). These data suggest that in an intact artery, NE released from
      sympathetic nerves stimulates alpha(1)-ARs to cause contraction and ERK
      activation, and that redundancy among subtypes exists for alpha(1)-AR activation
      of ERK.

PMID- 12235278
TI  - A cell-based reporter gene assay for determining induction of CYP3A4 in a high
      volume system.
AB  - Assessing the inducibility of CYP3A4 by various xenobiotics can predict potential
      drug interactions. In the present investigation, human hepatoma cells were stably
      integrated with either the CYP3A4 enhancer region and a luciferase reporter gene
      or the CYP3A4-luciferase construct and the human pregnane X receptor (PXR).
      Several colonies containing one to three copies of luciferase per cell were
      identified by Southern blot analysis. Those transformants producing high
      luciferase activity in response to rifampicin were used to standardize a 96-well
      plate screening system with minimal inter- and intraplate variability.
      Standardization also consisted of assessing viability of cells cultured in medium
      containing various serum concentrations. In cells maintained for 48 h in medium
      with less than 5% serum, a significant (p < 0.01) decline was observed in
      viability accompanied by altered induction. A defined serum-free medium also
      produced less viable cells but did not alter the inductive response. Treatment of
      transformants with various concentrations of rifampicin produced a dose-response
      curve with maximal induction at 10 microM (5.6 +/- 0.18- and 2.1 +/- 0.3-fold
      above dimethyl sulfoxide (DMSO)-treated cells in transformants with and without
      PXR, respectively). Of additional agents examined for their ability to induce
      CYP3A4, omeprazole (200 microM) was the most potent inducer (12.8 +/- 1.9- and
      2.4 +/- 0.2-fold above DMSO-treated cells in transformants with and without PXR,
      respectively). Mifepristone and mevastatin produced modest induction
      (approximately 3-fold) in the cell line containing exogenous PXR, but produced
      less than 1.2-fold increases in cells lacking PXR. Thus, only potent inducers can
      be identified in the cell line without PXR. In contrast, cells containing the
      receptor can be used to rank CYP3A4 induction. Because a high volume of chemicals
      can be readily and accurately screened for their ability to induce CYP3A4 with
      this format, such a system could be valuable in the initial stages of preclinical
      drug development.

PMID- 12235279
TI  - Characterization of nociceptin/orphanin FQ-induced pain responses by the novel
      receptor antagonist N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl)
      benzamide monohydrochloride.
AB  - At the spinal level, nociceptin/orphanin FQ (Noc/OFQ) produces pronociceptive and
      allodynic effects at low doses (picogram range), while causing antinociceptive
      effects at high doses (microgram range). The discrepancy of pain modulation by
      Noc/OFQ at low and high doses raised a question whether Noc/OFQ exerted actions
      through the same Noc/OFQ receptor. In the present study, we examined the
      involvement of the Noc/OFQ receptor in pain responses with the novel nonpeptide
      antagonist N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) benzamide
      monohydrochloride (JTC-801). Allodynia and hyperalgesia evoked by intrathecal
      administration of Noc/OFQ (50 pg/mouse) were dose dependently blocked by
      simultaneous administration of JTC-801 with IC(50) values of 32.2 and 363 pg,
      respectively. JTC-801 did not induce allodynia by itself. Subcutaneous injection
      of formalin into a hindpaw evoked biphasic pain behaviors such as flinching and
      biting in mice. Noc/OFQ at 10 pg increased the second-phase pain behaviors evoked
      by 1% formalin, whereas it strongly inhibited both the first-phase and second
      phase pain evoked by 2% formalin at 1 microg. Although the pronociceptive effect
      by 10 pg of Noc/OFQ was dose dependently blocked by JTC-801 with an IC(50) value
      of 4.58 pg, the antinociceptive effects by 1 microg of Noc/OFQ were not
      antagonized by JTC-801. Furthermore, both phases of 2% formalin-induced pain
      behaviors were relieved by JTC-801. These results demonstrate that pronociceptive
      responses induced by a low dose of Noc/OFQ may be mediated through the Noc/OFQ
      receptor in the spinal cord and that JTC-801 can be a useful antagonist to
      examine the involvement of endogenous Noc/OFQ and mediation of the Noc/OFQ
      receptor under physiological and pathophysiological conditions including pain.

PMID- 12235280
TI  - Meeting report for the ASPET Ray Fuller Symposium: lower urinary tract disorders:
      physiology, pharmacology, and therapeutic approaches.

PMID- 12235281
TI  - Intracellular calcium signaling.

PMID- 12235282
TI  - Metalloproteinase inhibitors: biological actions and therapeutic opportunities.
AB  - Tissue inhibitors of metalloproteinases (TIMPs) are the major cellular inhibitors
      of the matrix metalloproteinase (MMP) sub-family, exhibiting varying efficacy
      against different members, as well as different tissue expression patterns and
      modes of regulation. Other proteins have modest inhibitory activity against some
      of the MMPs, including domains of netrins, the procollagen C-terminal proteinase
      enhancer (PCPE), the reversion-inducing cysteine-rich protein with Kazal motifs
      (RECK), and tissue factor pathway inhibitor (TFPI-2), but their physiological
      significance is not at all clear. Alpha2-macroglobulin, thrombospondin-1 and
      thrombospondin-2 can bind to some MMPs and act as agents for their removal from
      the extracellular environment. In contrast, few effective inhibitors of other
      members of the metzincin family, the astacins or the distintegrin
      metalloproteinases, ADAMs have been identified. Many of these MMP inhibitors,
      including the TIMPs, possess other biological activities which may not be related
      to their inhibitory capacities. These need to be thoroughly characterized in
      order to allow informed development of MMP inhibitors as potential therapeutic
      agents. Over activity of MMPs has been implicated in many diseases, including
      those of the cardiovascular system, arthritis and cancer. The development of
      synthetic small molecule inhibitors has been actively pursued for some time, but
      the concept of the use of the natural inhibitors, such as the TIMPs, in gene
      based therapies is being assessed in animal models and should provide useful
      insights into the cell biology of degradative diseases.

PMID- 12235283
TI  - Get a ligand, get a life: integrins, signaling and cell survival.
AB  - Programmed cell death is crucial for the development and maintenance of
      multicellular organisms. The decision to live, or to die, depends, at the
      cellular level, upon the cell's interaction with extracellular cues that trigger
      cell signaling pathways promoting survival or death. The extracellular matrix
      (ECM) influences the execution of the apoptotic program through the actions of
      adhesion receptors. Among these, integrins initiate a variety of downstream
      signaling events in response to ECM ligation. Integrins directly activate
      survival pathways via the PI 3-kinase and MAPK pathways and act as essential
      cofactors for their stimulation by growth factors. Conversely, elevated integrin
      expression in the absence of appropriate ligands, or in the presence of natural
      or synthetic antagonists, can promote apoptosis under otherwise permissive growth
      conditions. Integrins thus act in a crucial biosensory role, coordinating
      survival or death responses as a function of ECM composition. This dual function
      provides an elegant mechanism through which tissue-remodeling events may regulate
      cell death or survival in a temporal, ECM-governed manner.

PMID- 12235284
TI  - Domains of type 1 protein phosphatase inhibitor-2 required for nuclear and
      cytoplasmic localization in response to cell-cell contact.
AB  - Inhibitor-2 of type 1 protein phosphatase is a phosphoprotein conserved among all
      eukaryotes, and it appears in both the nucleus and cytoplasm of tissue culture
      cells. We discovered that endogenous inhibitor-2 is concentrated in the nucleus
      of cells cultured at low density, whereas cells growing at high density excluded
      inhibitor-2 from the nucleus. There was rapid redistribution of inhibitor-2 when
      cells were replated at low or high density. Localization of myc-tagged forms of
      inhibitor-2 showed that residues 119-197 were required for nuclear accumulation
      in low-density cells and residues 78-119 were required for cytoplasmic
      localization in high-density cells. Fusion of inhibitor-2 residues 78-119 to
      green fluorescent protein was sufficient to produce cytoplasmic retention.
      Inhibitor-2 fused to triple tandem green fluorescent protein (100 kDa) was
      imported into the nucleus of low-density cells but was not excluded from the
      nucleus when cells reached high density, implying that inhibitor-2 was actively
      imported into the nucleus but exited by passive diffusion instead of active
      export. We conclude that inhibitor-2 contains two separate domains that control
      its localization in the nucleus or cytoplasm. This change in inhibitor-2
      localization may direct inhibitor-2 to different forms of protein phosphatase 1
      or change the localization of protein phosphatase, as part of the cellular
      response to cell-cell contacts at high density.

PMID- 12235285
TI  - Meiotic telomere clustering is inhibited by colchicine but does not require
      cytoplasmic microtubules.
AB  - Telomere clustering, the defining feature of the bouquet, is an almost universal
      feature of meiotic prophase, yet its mechanism remains unknown. The microtubule
      depolymerizing agent colchicine was found to inhibit bouquet formation. Telomeres
      in colchicine-treated cells remained scattered in the nuclear periphery, whereas
      untreated cells exhibited a prominent telomere cluster. Colchicine administered
      after the bouquet had formed did not affect telomere dispersal. The effect of
      colchicine on bouquet formation appeared to be separable from its effect on
      cytoplasmic microtubules; amiprophos methyl, a highly effective plant microtubule
      depolymerizing drug, did not affect telomere clustering. Inhibition of bouquet
      formation was limited to colchicine and the related drug podophyllotoxin out of
      the variety of microtubule-depolymerizing drugs tested, suggesting that the
      target involved in bouquet formation has a structural specificity.

PMID- 12235286
TI  - Reorganization and polarization of the meiotic bouquet-stage cell can be
      uncoupled from telomere clustering.
AB  - Striking cellular reorganizations mark homologous pairing during meiotic
      prophase. We address the interdependence of chromosomal and cellular polarization
      during meiotic telomere clustering, the defining feature of the bouquet stage, by
      examining nuclear positioning and microtubule and nuclear pore reorganization.
      Polarization of meiotic cellular architecture was coincident with telomere
      clustering: microtubules were focused on the nuclear surface opposite the
      telomere cluster, the nucleus was positioned eccentrically in the cell such that
      the telomeres faced the direction of nuclear displacement and nuclear pores were
      clustered in a single region of the nuclear surface opposite the telomeres.
      Treatment of pre-bouquet stage cells with colchicine inhibited telomere
      clustering. Asymmetric nuclear positioning and nuclear pore clustering were
      normal in the presence of unclustered telomeres resulting from colchicine
      treatment. Nuclear pores were positioned normally with respect to the cell cortex
      in the absence of telomere clustering, indicating that telomere positioning is
      not required for polarization. This work provides evidence of meiotic cell
      polarization and suggests that telomeres may be positioned relative to an
      asymmetry present in the cell at the time of bouquet formation.

PMID- 12235287
TI  - Epithelial monolayer wounding stimulates binding of USF-1 to an E-box motif in
      the plasminogen activator inhibitor type 1 gene.
AB  - Several proteases and their co-expressed inhibitors modulate the interdependent
      processes of cell migration and matrix proteolysis during wound repair.
      Transcription of the gene encoding plasminogen activator inhibitor type 1 (PAI
      1), a serine protease inhibitor important in the control of barrier proteolysis
      and cell-to-matrix adhesion, is spatially-temporally regulated following
      epithelial denudation injury in vitro as well as in vivo. Using a well-defined
      culture model of acute epidermal wounding and reepithelialization, PAI-1
      mRNA/protein synthesis was induced early after monolayer scraping and restricted
      to cells comprising the motile cohort. PAI-1 levels in locomoting cells remained
      elevated (relative to the distal, contact-inhibited monolayer regions) throughout
      the time course of trauma repair. Targeted PAI-1 downregulation by transfection
      of antisense PAI-1 expression constructs significantly impaired keratinocyte
      migration and monolayer scrape wound closure. Injury-induced PAI-1 transcription
      closely paralleled growth state-dependent controls on the PAI-1 gene. An E-box
      motif (CACGTG) in the PAI-1 proximal promoter (located at nucleotides -160 to 
      165), previously shown to be necessary for serum-induced PAI-1 expression, was
      bound by nuclear factors from wound-stimulated but not quiescent, contact
      inhibited, keratinocytes. UV crosslinking approaches to identify E-box-binding
      factors coupled with deoxyoligonucleotide affinity chromatography and gel
      retardation assays confirmed at least one major E-box-binding protein in both
      serum- and wound-activated cells to be USF-1, a member of the helix-loop-helix
      family of transcription factors. An intact hexanucleotide E-box motif was
      necessary and sufficient for USF-1 binding using nuclear extracts from both serum
      and wound-simulated cells. Two species of immunoreactive USF-1 were identified
      by western blotting of total cellular lysates that corresponded to the previously
      characterized phosphorylated and non-phosphorylated forms of the protein. USF-1
      isolated by PAI-1 promoter-DNA affinity chromatography was almost exclusively
      phosphorylated. Only a fraction of the total cellular USF-1 in proliferating
      cultures, by comparison, was phosphorylated at any given time. PAI-1 E-box
      binding activity, assessed by probe mobility shift criteria, increased within 2
      hours of monolayer scrape injury, a time frame consistent with wound-stimulated
      increases in PAI-1 transcription. Relative to intact cultures, scrape site
      juxtaposed cells had significantly greater cytoplasmic and nuclear USF-1
      immunoreactivity correlating with the specific in situ-restricted expression of
      PAI-1 transcripts/protein in the wound-edge cohort. USF-1 immunocytochemical
      staining declined significantly with increasing distance from the denudation
      site. These data are the first to indicate that binding of USF-1 to its target
      motif can be induced by 'tissue' injury in vitro and implicate USF-1 as a
      transcriptional regulator of genes (e.g. PAI-1) involved in wound repair.

PMID- 12235288
TI  - Retinoic acid receptor beta2 and neurite outgrowth in the adult mouse spinal cord
      in vitro.
AB  - Retinoic acid, acting through the nuclear retinoic acid receptor beta2
      (RARbeta2), stimulates neurite outgrowth from peripheral nervous system tissue
      that has the capacity to regenerate neurites, namely, embryonic and adult dorsal
      root ganglia. Similarly, in central nervous system tissue that can regenerate,
      namely, embryonic mouse spinal cord, retinoic acid also stimulates neurite
      outgrowth and RARbeta2 is upregulated. By contrast, in the adult mouse spinal
      cord, which cannot regenerate, no such upregulation of RARbeta2 by retinoic acid
      is observed and no neurites are extended in vitro. To test our hypothesis that
      the upregulation of RARbeta2 is crucial to neurite regeneration, we have
      transduced adult mouse or rat spinal cord in vitro with a minimal equine
      infectious anaemia virus vector expressing RARbeta2. After transduction, prolific
      neurite outgrowth occurs. Outgrowth does not occur when the cord is transduced
      with a different isoform of RARbeta nor does it occur following treatment with
      nerve growth factor. These data demonstrate that RARbeta2 is involved in neurite
      outgrowth, at least in vitro, and that this gene may in the future be of some
      therapeutic use.

PMID- 12235290
TI  - The growth of Drosophila bristles and laterals is not restricted to the tip or
      base.
AB  - The highly elongated bristles of Drosophila have proven to be a valuable model
      system for studying cellular morphogenesis. Extending bristles contain a series
      of large bundles of actin filaments juxtaposed to the plasma membrane and
      centrally located microtubules. Models to explain the extension of the bristle
      have principally focused on the assembly of actin filaments at the distal tip of
      the bristle. We have used time-lapse observations of wild-type and mutant
      bristles and the related arista laterals and come to the conclusion that growth
      takes place throughout the growing cellular extension. This distributed growth
      can explain the behavior of split laterals and the shape changes seen at the tip
      during bristle and lateral outgrowth. Inhibitor studies suggest that the
      microtubule cytoskeleton is essential for maintaining the highly biased axial
      growth of these structures. We have used fluorescence recovery after photo
      bleaching to study the dynamics of the cytoskeleton during bristle growth. Our
      experiments show that actin bundles in growing bristles are quite stable and move
      in a retrograde fashion. The bristle microtubules are less stable. The retrograde
      movement of the peripheral actin appears to be counterbalanced by the distally
      directed movement of cytoplasm in the center of the bristle.

PMID- 12235291
TI  - Src family tyrosine kinases regulate adhesion-dependent tyrosine phosphorylation
      of 5'-inositol phosphatase SHIP2 during cell attachment and spreading on collagen
      I.
AB  - Inositol phosphatases play an important role in regulation of cellular levels of
      lipid second messengers. Recently we have reported a novel function for SHIP2 in
      cell adhesion and spreading. In this study, we further characterize the adhesion
      dependent tyrosine phosphorylation of SHIP2 and examine the role of Src family
      tyrosine kinases in the regulation of SHIP2 function. SHIP2 was tyrosine
      phosphorylated during cell attachment and spreading on collagen I, but not on
      fibronectin, collagen IV, laminin or poly-L-lysine. SHIP2 tyrosine
      phosphorylation, induced by plating on a collagen-I-coated surface but not by
      epidermal growth factor or insulin treatment of cells, was completely blocked by
      small molecule inhibitors of Src family kinases. SHIP2 could be phosphorylated in
      vitro by recombinant Src kinase and tyrosines 986-987 in the NPXY motif of SHIP2
      appear to be the major sites of phosphorylation for Src both in vitro and in
      vivo. An activated form of Src induced strong tyrosine phosphorylation of SHIP2
      while a dominant-negative form decreased collagen-I-dependent SHIP2
      phosphorylation. SHIP2 associated with the adapter protein Shc via its NPXY motif
      during cell spreading on collagen I in a Src activity-dependent manner.
      Expression of SHIP2 with mutated NPXY motif caused deregulation of lamellipodia
      formation during spreading on collagen I. These observations indicate that SHIP2
      is regulated by Src family kinases during cell attachment and spreading on
      collagen I and suggest an important role for SHIP2 as a part of a signaling
      pathway that regulates actin cytoskeleton remodeling.

PMID- 12235289
TI  - Anaphase onset does not require the microtubule-dependent depletion of
      kinetochore and centromere-binding proteins.
AB  - Spindle checkpoint proteins, such as Mad2 and BubR1, and the motors
      dynein/dynactin and CENP-E usually leave kinetochores prior to anaphase onset by
      microtubule-dependent mechanisms. Likewise, 'chromosome passenger proteins'
      including INCENP are depleted from the centromeres after anaphase onset and then
      move to the midzone complex, an event that is essential for cytokinesis. Here we
      test whether the cell cycle changes that occur at anaphase onset require or
      contribute to the depletion of kinetochore and centromere proteins independent of
      microtubules. This required the development of a novel non-antibody method to
      induce precocious anaphase onset in vivo by using a bacterially expressed
      fragment of the spindle checkpoint protein Mad1 capable of activating the APC/C,
      called GST-Mad1F10. By injecting PtK1 cells in nocodazole with GST-Mad1F10 and
      processing the cells for immunofluorescence microscopy after anaphase sister
      chromatid separation in nocodazole we found that Mad2, BubR1, cytoplasmic dynein,
      CENP-E and the 3F3/2 phosphoepitope remain on kinetochores. Thus depletion of
      these proteins (or phosphoepitope) at kinetochores is not required for anaphase
      onset and anaphase onset does not produce their depletion independent of
      microtubules. In contrast, both microtubules and anaphase onset are required for
      depletion of the 'chromosome passenger' protein INCENP from centromeres, as
      INCENP does not leave the chromosomes prior to anaphase onset in the presence or
      absence of microtubules, but does leave the centromeres after anaphase onset in
      the presence of microtubules.

PMID- 12235293
TI  - Spatial organisation and behaviour of the parental chromosome sets in the nuclei
      of Saccharomyces cerevisiae x S. paradoxus hybrids.
AB  - We demonstrate that the genomes of Saccharomyces cerevisiae and S. paradoxus are
      sufficiently divergent to allow their differential labeling by genomic in situ
      hybridisation (GISH). The cytological discrimination of the genomes allowed us to
      study the merging of the two genomes during hybrid mating. GISH revealed that in
      hybrid nuclei the two genomes are intermixed. In hybrid meiosis, extensive
      intraspectific nonhomologous pairing takes place. GISH on chromosome addition and
      substitution strains (with chromosomes of S. paradoxus added to or replacing the
      homoeologous chromosome of an otherwise S. cerevisiae background) was used to
      delineate individual chromosomes at interphase and to examine various aspects of
      chromosome structure and arrangement.

PMID- 12235292
TI  - Visualization of translated tau protein in the axons of neuronal P19 cells and
      characterization of tau RNP granules.
AB  - Localization of tau mRNA to the axon requires the axonal localization cis signal
      (ALS), which is located within the 3' untranslated region, and trans-acting
      binding proteins, which are part of the observed granular structures in neuronal
      cells. In this study, using both biochemical and morphological methods, we show
      that the granules contain tau mRNA, HuD RNA-binding protein, which stabilizes
      mRNA, and KIF3A, a member of the kinesin microtubule-associated motor protein
      family involved in anterograde transport. The granules are detected along the
      axon and accumulate in the growth cone. Inhibition of KIF3A expression caused
      neurite retraction and inhibited tau mRNA axonal targeting. Taken together, these
      results suggest that HuD and KIF3A proteins are present in the tau mRNA axonal
      granules and suggest an additional function for the kinesin motor family in the
      microtubule-dependent translocation of RNA granules. Localized tau-GFP expression
      was blocked by a protein synthesis inhibitor, and upon release from inhibition,
      nascent tau-GFP 'hot spots' were directly observed in the axon and growth cones.
      These observations are consistent with local protein synthesis in the axon
      resulting from the transported tau mRNA.

PMID- 12235294
TI  - Osteoclast spreading kinetics are correlated with an oscillatory activation of a
      calcium-dependent potassium current.
AB  - Cell movement and spreading involve calcium-dependent processes and ionic channel
      activation. During bone resorption, osteoclasts alternate between spread, motile
      and resorptive phases. We investigated whether the electrical membrane properties
      of osteoclasts were linked to their membrane morphological changes. Rabbit
      osteoclasts were recorded by time-lapse videomicroscopy performed simultaneously
      with patch-clamp whole cell and single channel recordings. Original image
      analysis methods were developed and used to demonstrate for the first time an
      oscillatory activation of a spontaneous membrane current in osteoclasts, which is
      directly correlated to the membrane movement rate. This current was identified as
      a calcium-dependent potassium current (IK(Ca)) that is sensitive to both
      charybdotoxin and apamin and was generated by a channel with unitary conductance
      of approximately 25+/-2 pS. Blockade of this current also decreased osteoclast
      spreading and inhibited bone resorption in vitro, demonstrating a physiological
      role for this current in osteoclast activity. These results establish for the
      first time a temporal correlation between lamellipodia formation kinetics and
      spontaneous peaks of IK(Ca), which are both involved in the control of osteoclast
      spreading and bone resorption.

PMID- 12235295
TI  - Improperly folded green fluorescent protein is secreted via a non-classical
      pathway.
AB  - The green fluorescent protein is a cytosolic protein frequently used as a
      molecular tag to study protein localization in intact cells. We discovered that
      this protein is secreted into the medium by several but not all cell lines
      through a non-classical secretory pathway that is insensitive to brefeldin A.
      Green fluorescent protein is secreted efficiently by Chinese hamster ovary cells,
      with 60% of synthesized proteins secreted over 8 hours. This pathway is sensitive
      to changes in temperature but not to factors in serum or chemicals known to
      affect other non-classical protein secretion pathways. Fluorescence is observed
      in cells expressing green fluorescent protein, indicating that some of the
      protein must be fully folded in the cytosol. However, secreted green fluorescent
      protein is not fluorescent and therefore not folded properly. Furthermore,
      cellular fluorescence does not change over 6 hours whereas a significant
      proportion of green fluorescent protein is secreted. Thus, nascent green
      fluorescent protein either is folded correctly or incorrectly, and the improperly
      folded molecules can be exported. Non-classical secretion might be a route by
      which cells remove an excess of improperly folded, cytosolic proteins.

PMID- 12235296
TI  - The vegetative state.

PMID- 12235297
TI  - Cognitive neuroscience and brain rehabilitation: a promise kept.

PMID- 12235298
TI  - Infection and multiple sclerosis--a new hypothesis?

PMID- 12235299
TI  - We are how we eat?

PMID- 12235300
TI  - The Babinski sign.
AB  - Babinski's life and the story of the Babinski sign are summarised. The
      physiological basis of the sign is discussed.

PMID- 12235302
TI  - Changes in appetite, food preference, and eating habits in frontotemporal
      dementia and Alzheimer's disease.
AB  - BACKGROUND: Despite numerous reports of changes in satiety, food preference, and
      eating habits in patients with frontotemporal dementia, there have been few
      systematic studies. OBJECTIVES: To investigate the frequency of changes in eating
      behaviours and the sequence of development of eating behaviours in frontotemporal
      dementia and Alzheimer's disease, using a caregiver questionnaire. METHODS: Three
      groups of patients were studied: frontal variant frontotemporal dementia (fv-FTD)
      (n = 23), semantic dementia (n = 25), and Alzheimer's disease (n = 43). Level of
      education and dementia severity was similar in the three groups. The
      questionnaire consisted of 36 questions investigating five domains: swallowing
      problems, appetite change, food preference, eating habits, and other oral
      behaviours. RESULTS: The frequencies of symptoms in all five domains, except
      swallowing problems, were higher in fv-FTD than in Alzheimer's disease, and
      changes in food preference and eating habits were greater in semantic dementia
      than in Alzheimer's disease. In semantic dementia, the developmental pattern was
      very clear: a change in food preference developed initially, followed by appetite
      increase and altered eating habits, other oral behaviours, and finally swallowing
      problems. In fv-FTD, the first symptom was altered eating habits or appetite
      increase. In Alzheimer's disease, the pattern was not clear although swallowing
      problems developed in relatively early stages. CONCLUSIONS: Change in eating
      behaviour was significantly more common in both of the frontotemporal dementia
      groups than in Alzheimer's disease. It is likely that the changing in eating
      behaviours reflects the involvement of a common network in both variants of
      frontotemporal dementia-namely, the ventral (orbitobasal) frontal lobe, temporal
      pole, and amygdala.

PMID- 12235301
TI  - The genetic basis of Parkinson's disease.
AB  - Although the mechanisms underlying neurodegeneration in Parkinson's disease are
      not fully understood, considerable evidence suggests that genetic factors can
      influence susceptibility to the disease. In this article, we critically review
      this evidence and examine studies estimating patterns of inheritance. In a few
      families, Parkinson's disease is clearly inherited in a Mendelian fashion, and in
      some of these the disease causing genes have already been identified. Possible
      pathogenic mechanisms by which these genes cause Parkinson's disease are
      discussed. Further candidate genes and systematic efforts to identify genes
      influencing susceptibility to the disease in general are also summarised. The
      identification of such susceptibility genes will eventually enable us to more
      accurately classify this complex disease.

PMID- 12235303
TI  - Abnormal verbal event related potentials in mild cognitive impairment and
      incipient Alzheimer's disease.
AB  - BACKGROUND: It has been reported that patients with amnesia have a reduced effect
      of word repetition upon the late positive component of the event related
      potential (ERP), which peaks at around 600 ms after word onset. OBJECTIVE: To
      study a word repetition ERP paradigm in subjects with mild cognitive impairment.
      SUBJECTS: 14 patients with mild cognitive impairment (mean mini-mental state
      examination score = 27); 14 normal elderly controls. METHODS: Auditory category
      statements were each followed by a single visual target word (50% "congruous"
      category exemplars, 50% "incongruous") while ERPs were recorded. N400 (an ERP
      component elicited by semantically "incongruous" words) and LPC amplitude data
      were submitted to analysis of variance. RESULTS: The latency of the N400 was
      slower in mild cognitive impairment. In normal controls, the ERPs to "congruous"
      targets showed a late positive component to new words, which was greatly
      diminished with repetition. This repetition effect in normal subjects started
      before 300 ms at right frontal sites, and peaked at approximately 600 ms post
      stimulus over posterior sites. In contrast, the group with mild cognitive
      impairment had a reduced repetition effect (p < 0.02), which started around 500
      ms, with a more central distribution. Further comparisons within the cognitive
      impairment group showed no appreciable congruous word repetition effect among
      seven individuals who subsequently converted to probable Alzheimer's disease. The
      congruous word repetition effect in the group with mild cognitive impairment was
      almost entirely accounted for by the non-converters. The amplitude of the
      congruous late positive component word repetition effect was significantly
      correlated (0.38 < or = r < or = 0.73) with several verbal memory measures.
      CONCLUSIONS: The congruous word repetition ERP effect appears sensitive to the
      memory impairment in mild cognitive impairment and could have value in predicting
      incipient Alzheimer's disease.

PMID- 12235304
TI  - Testing cognitive function in elderly populations: the PROSPER study. PROspective
      Study of Pravastatin in the Elderly at Risk.
AB  - OBJECTIVES: For large scale follow up studies with non-demented patients in which
      cognition is an endpoint, there is a need for short, inexpensive, sensitive, and
      reliable neuropsychological tests that are suitable for repeated measurements.
      The commonly used Mini-Mental-State-Examination fulfils only the first two
      requirements. METHODS: In the PROspective Study of Pravastatin in the Elderly at
      Risk (PROSPER), 5804 elderly subjects aged 70 to 82 years were examined using a
      learning test (memory), a coding test (general speed), and a short version of the
      Stroop test (attention). Data presented here were collected at dual baseline,
      before randomisation for active treatment. RESULTS: The tests proved to be
      reliable (with test/retest reliabilities ranging from acceptable (r=0.63) to high
      (r=0.88) and sensitive to detect small differences in subjects from different age
      categories. All tests showed significant practice effects: performance increased
      from the first measurement to the first follow up after two weeks. CONCLUSION:
      Normative data are provided that can be used for one time neuropsychological
      testing as well as for assessing individual and group change. Methods for
      analysing cognitive change are proposed.

PMID- 12235305
TI  - Potentially reversible conditions in 1000 consecutive memory clinic patients.
AB  - OBJECTIVES: To investigate the prevalence and classification of potentially
      reversible conditions in a prospective memory clinic cohort of younger and
      elderly patients with cognitive symptoms. PATIENTS: 1000 consecutive patients
      referred during a period of 54 months to a university hospital multidisciplinary
      memory clinic based in neurology. METHODS: All patients were referred for
      diagnostic evaluation and treatment of cognitive symptoms. The multidisciplinary
      staff prospectively established a standardised consensus report for each patient
      based on the results of clinical and ancillary investigations with classification
      of cognitive profile, primary underlying cause, and concomitant conditions.
      RESULTS: The mean age of the patients was 66.1 years (range 17-98) and 43% met
      diagnostic criteria for dementia. A potentially reversible primary aetiology for
      cognitive symptoms was identified in 19% and a potentially reversible concomitant
      condition in 23% of all patients. In the subgroup of patients with dementia, 4%
      had a potentially reversible primary aetiology. Careful clinical examination,
      routine laboratory tests, and cranial computed tomography identified most of
      these conditions. CONCLUSIONS: Reversible conditions are most often encountered
      in patients with mild cognitive disturbances. Although treatment may not always
      result in full reversal of cognitive symptoms, potentially reversible conditions
      should be identified in the diagnostic evaluation of the patient.

PMID- 12235306
TI  - Pituitary tumours and acromegaly (Pierre Marie's disease).

PMID- 12235307
TI  - Effect of chronic pallidal deep brain stimulation on off period dystonia and
      sensory symptoms in advanced Parkinson's disease.
AB  - OBJECTIVE: To investigate the efficacy of chronic pallidal deep brain stimulation
      (DBS) on off period dystonia, cramps, and sensory symptoms in advanced
      Parkinson's disease (PD). METHODS: 16 patients (6 women, 10 men; mean age at
      surgery 65 years) suffering from advanced PD were followed up prospectively for
      one year after implantation of a monopolar electrode in the posteroventral
      lateral globus pallidus internus. Unilateral DBS was performed in 9 patients. 10
      patients had bilateral procedures (contemporaneous bilateral surgery in 7 and
      staged bilateral surgery in 3 instances). The decision whether to perform
      unilateral or bilateral surgery depended on the clinical presentation of the
      patient. Patients were formally assessed preoperatively, at 3-5 days, 3 months,
      and 12 months after surgery. RESULTS: In patients who underwent unilateral
      surgery, pain was present in 7 (78%), off dystonia in 5 (56%), cramps in 6 (67%),
      and dysaesthesia in 4 (44%). In patients who underwent bilateral surgery, pain
      was present in 7 (70%), off dystonia in 6 (60%), cramps in 7 (70%), and
      dysaesthesia in 4 (40%). With unilateral DBS, contralateral off period dystonia
      was improved by 100% at 1 year postoperatively, pain by 74%, cramps by 88%, and
      dysaesthesia by 100%. There was less pronounced amelioration of ipsilateral off
      period dystonia and sensory symptoms. With bilateral DBS, total scores for
      dystonia were improved by 86%, for pain by 90%, for cramps by 90%, and for
      dysaesthesia by 88%. The benefit appeared early at the first evaluation 3-5 days
      after surgery and was stable throughout the follow up period. CONCLUSIONS:
      Pallidal DBS yields major improvement of off period dystonia, cramps, and sensory
      symptoms in patients with advanced PD.

PMID- 12235308
TI  - Essential tremor and cerebellar dysfunction: abnormal ballistic movements.
AB  - BACKGROUND: Clinical characteristics reminiscent of cerebellar tremor occur in
      patients with advanced essential tremor. Ballistic movements are known to be
      abnormal in cerebellar disease. The hypothesis was proposed that ballistic
      movements are abnormal in essential tremor, reflecting cerebellar dysfunction.
      OBJECTIVE: To elucidate the role of the cerebellum in the pathophysiology of
      essential tremor. METHODS: Kinematic parameters and the triphasic
      electromyographic (EMG) components of ballistic flexion elbow movements were
      analysed in patients assigned to the following groups: healthy controls (n = 14),
      pure essential postural tremor (ET(PT); n = 17), and essential tremor with an
      additional intention tremor component (ET(IT); n = 15). RESULTS: The main
      findings were a delayed second agonist burst (AG(2)) and a relatively shortened
      deceleration phase compared with acceleration in both the essential tremor
      groups. These abnormalities were most pronounced in the ET(IT) group, which had
      additional prolongation of the first agonist burst (AG(1)) and a delayed
      antagonist burst (ANT). CONCLUSIONS: Abnormalities of the triphasic pattern and
      kinematic parameters are consistent with a disturbed cerebellar timing function
      in essential tremor. These abnormalities were most pronounced in the ET(IT)
      group. The cerebellar dysfunction in essential tremor could indicate a basic
      pathophysiological mechanism underlying this disorder. ET(PT) and ET(IT) may
      represent two expressions within a continuous spectrum of cerebellar dysfunction
      in relation to the timing of muscle activation during voluntary movements.

PMID- 12235309
TI  - Oropharyngeal swallowing in craniocervical dystonia.
AB  - OBJECTIVE: To clarify the pathophysiology of dysphagia by electrophysiological
      methods. METHOD: Electrophysiological methods related to oropharyngeal swallowing
      were used to investigate 25 patients with cervical dystonia and 25 age matched
      normal volunteers. RESULTS: Dysphagia was suspected in 36% of patients with
      cervical dystonia on the basis of clinical assessment. The incidence of dysphagia
      increased to 72% on electrophysiological evaluation of pharyngeal swallowing.
      Submental muscle electromyographic (EMG) and laryngeal relocation times were
      significantly prolonged and the triggering time to swallowing reflex was
      significantly delayed. Some abnormalities seen in cricopharyngeal sphincter
      muscle EMG indicated that the striated sphincter muscle is hyperreflexive in some
      patients. CONCLUSION: Neurogenic dysphagia was more prominent and longer lasting
      than mechanical dysphagia, which was transient and varied from patient to
      patient. Although these electrophysiological methods were not suitable for
      detecting anatomical changes during swallowing, as in videofluoroscopic studies,
      observations supported the neurogenic cause of dysphagia in patients with any
      kind of cervical dystonia.

PMID- 12235310
TI  - Neck muscle vibration induces lasting recovery in spatial neglect.
AB  - OBJECTIVES: To evaluate whether neck muscle vibration is an effective technique
      for neglect rehabilitation, with lasting beneficial effects. METHODS: The effects
      of differential treatment of visual exploration training alone or in combination
      with neck muscle vibration were evaluated in a crossover study of two matched
      groups of 10 patients suffering from left sided neglect. Each group received a
      sequence of 15 consecutive sessions of exploration training and combined
      treatment. The effects of treatment were assessed with respect to different
      aspects of the neglect disorder such as impaired perception of the egocentric
      midline, exploration deficits in visual and tactile modes, and visual size
      distortion. The transfer of treatment effects to activities of daily living was
      examined by a reading test and a questionnaire of neglect related everyday
      problems. All variables were measured six times: three baseline measurements, two
      post-treatment measurements, and one follow up after two months. RESULTS: The
      results showed superior effects of combination treatment. A specific and lasting
      reduction in the symptoms of neglect was achieved in the visual mode, which
      transferred to the tactile mode with a concomitant improvement in activities of
      daily living. The improvement was evident two months after the completion of
      treatment. In contrast, isolated exploration training resulted in only minor
      therapeutic benefits in visual exploration without any significant transfer
      effects to other tasks. CONCLUSIONS: Neck muscle vibration is a decisive factor
      in the rehabilitation of spatial neglect and induces lasting recovery when given
      as a supplement to conventional exploration training.

PMID- 12235312
TI  - Periodic limb movement syndrome.

PMID- 12235311
TI  - Myopathy with antibodies to the signal recognition particle: clinical and
      pathological features.
AB  - OBJECTIVES: To study myopathies with serum antibodies to the signal recognition
      particle (SRP), an unusual, myositis specific antibody associated syndrome that
      has not been well characterised pathologically. METHODS: Clinical, laboratory,
      and myopathological features were evaluated in seven consecutive patients with a
      myopathy and serum anti-SRP antibodies, identified over three years. The anti-SRP
      myopathy was compared with myopathology in other types of inflammatory and immune
      myopathies. RESULTS: The patients with anti-SRP antibodies developed weakness at
      ages ranging from 32 to 70 years. Onset was seasonal (August to January).
      Weakness became severe and disability developed rapidly over a period of months.
      Muscle pain and fatigue were present in some patients. No patient had a
      dermatomyositis-like rash. Serum creatine kinase was very high (3000 to 25 000
      IU/l). Muscle biopsies showed an active myopathy, including muscle fibre necrosis
      and regeneration. There was prominent endomysial fibrosis, but little or no
      inflammation. Endomysial capillaries were enlarged, reduced in number, and
      associated with deposits of the terminal components of complement (C5b-9,
      membrane attack complex). Strength improved in several patients after
      corticosteroid treatment. CONCLUSIONS: Myopathies associated with anti-SRP
      antibodies may produce severe and rapidly progressive weakness and disability.
      Muscle biopsies show active myopathy with pathological changes in endomysial
      capillaries but little inflammation. Corticosteroid treatment early in the course
      of the illness is often followed by improvement in strength. In patients with
      rapidly progressive myopathies and a high serum creatine kinase but little
      inflammation on muscle biopsy, measurement of anti-SRP antibodies and
      pathological examination of muscle, including evaluation of endomysial
      capillaries, may provide useful information on diagnosis and treatment.

PMID- 12235314
TI  - Tuberous sclerosis presenting in late adult life.
AB  - A 59 year old woman presented with a three year history of left sided weakness.
      Magnetic resonance imaging of the brain showed a large high signal lesion
      occupying most of the right temporal lobe with mass effect. A probable diagnosis
      of low grade glioma led to temporal lobectomy. Histology revealed dysplastic
      cortical morphology typical of tuberous sclerosis. There were no clinical signs
      or family history of the disease. Ultrasound showed multiple bilateral renal
      angiomyolipomas, confirming the diagnosis of tuberous sclerosis. Molecular
      genetic analysis of peripheral white blood cells identified a novel mis-sense
      mutation R1409W in exon 33 of the TSC2 gene.

PMID- 12235313
TI  - Optic neuromyelitis syndrome in Brazilian patients.
AB  - OBJECTIVES: To report the clinical features and outcome of 24 Brazilian patients
      with optic neuromyelitis syndrome (ONM); discuss the underlying pathological
      events associated with the ONM syndrome; review the nosological situation of ONM
      in the group of inflammatory and demyelinating diseases of the central nervous
      system. PATIENTS AND METHODS: Patients with ONM treated at the Hospital da Lagoa,
      Rio de Janeiro were studied. Demographic, clinical, magnetic resonance imaging,
      cerebrospinal fluid, and pathological data were analysed. RESULTS: The study
      consisted of 20 women, four men of whom 10 were white and 14 Afro-Brazilians.
      Clinical course was recurrent in 22 cases and monophasic in two. Neurological
      manifestations at inclusion were: sensory impairment (66%), bilateral (41.6%) or
      unilateral blindness (20.8%), paraplegia or quadriplegia (37.5%). The EDSS was
      moderate/severe in 70.8%. The underlying pathological events were respectively
      pulmonary tuberculosis and upper respiratory infection in the two monophasic
      cases; in the 22 recurrent ONM patients: pulmonary tuberculosis (3),
      neurocysticercosis (1), polyarteritis nodosa (1), antinuclear antibody and
      rheumatoid factor (1), antiphospholipid antibody primary syndrome (1), diabetes
      mellitus (1), hypothyroidism (1), and amenorrhea-galactorrhea (4). Normal
      cerebrospinal fluid was found in 52% and an inflammatory profile in 48%. Only
      four recurrent ONM white patients had brain and spinal cord magnetic resonance
      imaging and cerebrospinal fluid findings compatible with the diagnosis of
      multiple sclerosis. Large lesions were seen in 62% of spinal magnetic resonance
      images. Six of 12 recurrent ONM Afro-Brazilian died. There were no statistical
      differences in the demographic data of the two ethnic groups. Afro-Brazilians
      were significantly more severely impaired and had a higher mortality rate than
      the white patients. CONCLUSION: These cases were classified as follows: two
      monophasic acute disseminated encephalomyelitis; one recurrent disseminated
      encephalomyelitis; three recurrent ONM associated with Hughes syndrome,
      autoantibodies and polyarteritis nodosa; six recurrent ONM with endocrinopathies;
      and finally, four multiple sclerosis cases. The remaining cases were not
      associated with any other condition. It would seem clear that ONM is a syndrome
      rather than a single disease.

PMID- 12235315
TI  - Nikolai Nilovich Burdenko (1876-1946).

PMID- 12235316
TI  - Is multiple sclerosis a sexually transmitted infection?
AB  - It is proposed that multiple sclerosis may be transmitted chiefly by sexual
      contact. Arguments favouring this include: migration studies that suggest a
      transmissible agent in adolescence; clusters of multiple sclerosis which have
      occurred in low prevalence areas following entry of young males; the similarity
      of multiple sclerosis to tropical spastic paraplegia, a known sexually
      transmitted infection with resemblance to primary progressive multiple sclerosis;
      an increased rate in drug misusers; a similar age of onset and sex pattern to
      that found in sexually transmitted disease; increased incidence of multiple
      sclerosis in those using oral contraceptives; low multiple sclerosis rates in
      societies with a strict moral code; longitudinal shifts in sex prevalence that
      show an increase in women after the sexual revolution of the 1960s; and important
      exceptions to the worldwide distribution corresponding to countries with
      permissive attitudes to sex. Family, conjugal pair, twin, and adoption studies
      are compatible with an infectious cause of multiple sclerosis if this is sexually
      transmitted. It is not proposed that sexual transmission is the only cause but
      that inherited factors create a susceptibility to a sexually transmitted
      neurotropic agent. It is hoped this hypothesis might encourage a new direction of
      neurological research.

PMID- 12235317
TI  - Neuropsychological sequelae of bilateral posteroventral pallidotomy.
AB  - OBJECTIVES: To document the impact of bilateral posteroventral pallidotomy on
      cognitive status. METHODS: 17 patients with Parkinson's disease were evaluated
      with a neuropsychological battery before and six months after bilateral
      pallidotomy. A comparison group (n = 8) was also assessed at six month intervals.
      Outcome variables were tests of memory, language, visuospatial function,
      attention, executive skills, and depression. RESULTS: Despite a large number of
      variables studied, a significant postsurgical change was found only in
      performance of the tower of London task, a measure of planning abilities. The
      effect size of this change was larger than that of the comparison group, and a
      reliable change index score established that 5 of 13 surgical patients had
      statistically reliable reductions in planning performance. CONCLUSIONS: Patients
      with a young age of onset and long duration of Parkinson's disease who underwent
      bilateral pallidotomy had a relatively circumscribed reduction in
      neuropsychological functioning, being limited to motor planning efficiency. These
      data suggest that the cognitive role of the posteroventral globus pallidus is
      limited, at least in people with Parkinson's disease.

PMID- 12235318
TI  - Posterior alien hand syndrome after a right thalamic infarct.
AB  - The alien hand syndrome, as originally defined, should be reserved for cases in
      which the hand feels foreign "together with" observable involuntary motor
      activity. These involuntary movements are unusual during or after acute stroke.
      Three varieties of alien hand syndrome have been reported, involving lesions of
      the corpus callosum alone, the corpus callosum plus dominant medial frontal
      cortex, and posterior cortical and subcortical areas. A patient with posterior
      alien hand syndrome of vascular aetiology is reported. Imaging studies disclosed
      an isolated infarction of the right thalamus sparing other cerebral regions.

PMID- 12235319
TI  - Paradoxical absence of nuclear inclusion in cerebellar Purkinje cells of
      hereditary ataxias linked to CAG expansion.
AB  - Degeneration of cerebellar cortex is one of the principal features of hereditary
      ataxias linked to expansion of CAG repeat. In an attempt to clarify possible
      correlation between neuronal depletion and neuronal intranuclear inclusions, both
      triggered by the pathological expansion of CAG repeat, cerebellar sections from
      SCA1, SCA2, SCA3, and DRPLA cases were immunostained with anti-ubiquitin or anti
      expanded polyglutamine antibody (1C2) and were screened for the presence of
      neuronal intranuclear inclusions. Although the degree of cerebellar degeneration
      varied greatly, cerebellar Purkinje cells were uniformly characterised by the
      absence of neuronal intranuclear inclusion. Complete absence of neuronal
      intranuclear inclusion in Purkinje cells is apparently paradoxical and hardly
      explained if neuronal intranuclear inclusion formation is positively correlated
      to a mechanism accelerating neuronal death. It may, otherwise, suggest an
      intrinsic link between neuronal intranuclear inclusion formation and
      neurodegeneration in opposite directions in human Purkinje cells, more or less
      affected in these CAG repeat disorders.

PMID- 12235320
TI  - Vim thalamotomy for Holmes' tremor secondary to midbrain tumour.
AB  - Holmes' (rubral or midbrain) tremor is an unusual combination of 2 Hz to 5 Hz
      rest, postural, and kinetic tremors of an upper extremity. This tremor has been
      considered to result from the lesions in the vicinity of the red nucleus in the
      midbrain. There has been no systematic analysis of the surgical target in the
      Holmes' tremor so far of nucleus ventrointermedius (Vim) or globus pallidus
      interna. This 26 year old man gradually developed a disabling midbrain tremor
      involving both the distal and proximal parts of the left upper arm. Additional
      neurological findings included oculomotor palsy and ataxia of the left arm. On
      the radiological studies, a mass lesion (germinoma) was found on the midbrain
      tegmentum, which was treated by conventional radiation therapy. Although there
      was improvement in the radiological imaging, his midbrain tremor became
      intolerable despite medical treatment. The authors performed MR guided
      stereotactic Vim thalamotomy. With radiofrequency lesioning in the right Vim, his
      resting, postural, and action tremors were much alleviated in both the distal and
      proximal parts of the left upper extremity. The authors consider that Vim
      thalamotomy is still an effective means of controlling midbrain tremors involving
      the proximal upper limb.

PMID- 12235321
TI  - Increased serum concentrations of tissue plasminogen activator correlate with an
      adverse clinical outcome in patients with bacterial meningitis.

PMID- 12235322
TI  - Amelioration of spinal myoclonus with levetiracetam.

PMID- 12235323
TI  - Coma with focal neurological signs caused by Datura stramonium intoxication in a
      young man.

PMID- 12235324
TI  - Hyperthyroidism with increased factor VIII procoagulant protein as a predisposing
      factor for cerebral venous thrombosis.

PMID- 12235325
TI  - Neuropathological findings in multiple system atrophy with dystonia.

PMID- 12235326
TI  - Neuropsychological and psychiatric complications in endoscopic third
      ventriculostomy.

PMID- 12235327
TI  - Social phobia in spasmodic torticollis: some conceptual issues.

PMID- 12235328
TI  - Executive dysfunction and depressive symptoms in cerebrovascular disease.

PMID- 12235330
TI  - Complications of ureteral stent placement.
AB  - The recent increase in usage of ureteral stents in the management of a variety of
      urinary tract disease processes mandates familiarity with these devices, their
      consequences, and their potential complications, which at times can be
      devastating. Radiology plays an important role in the routine monitoring of
      stents and in the evaluation of these consequences and complications. It may also
      offer solutions for their correction. Stents should be monitored while in place,
      promptly removed when no longer needed, and changed periodically if chronically
      indwelling. Risk factors for complications should be minimized with high fluid
      intake, timely evaluation of clinical complaints, and aggressive treatment of
      documented infection. Certain patients may not be best served by indwelling stent
      placement, and urinary diversion by means of other mechanisms may be indicated.
      The implanting physician is responsible for informing the patient of the
      requirements, consequences, and complications associated with stent placement.
      Failure to do so has obvious management and potential medicolegal implications.

PMID- 12235331
TI  - Benign versus malignant hepatic nodules: MR imaging findings with pathologic
      correlation.
AB  - According to the currently used nomenclature, there are only two types of
      hepatocellular nodular lesions: regenerative lesions and dysplastic or neoplastic
      lesions. Regenerative nodules include monoacinar regenerative nodules,
      multiacinar regenerative nodules, cirrhotic nodules, segmental or lobar
      hyperplasia, and focal nodular hyperplasia. Dysplastic or neoplastic nodules
      include hepatocellular adenoma, dysplastic foci, dysplastic nodules, and
      hepatocellular carcinoma (HCC). Many of these types of hepatic nodules play a
      role in the de novo and stepwise carcinogenesis of HCC, which comprises the
      following steps: regenerative nodule, low-grade dysplastic nodule, high-grade
      dysplastic nodule, small HCC, and large HCC. State-of-the-art magnetic resonance
      (MR) imaging facilitates detection and characterization in most cases of hepatic
      nodules. State-of-the-art MR imaging includes single-shot fast spin-echo imaging,
      in-phase and opposed-phase T1-weighted gradient-echo imaging, T2-weighted fast
      spin-echo imaging with fat saturation, and two-dimensional or three-dimensional
      dynamic multiphase contrast material-enhanced imaging.

PMID- 12235333
TI  - Collaboration system for radiology workstations.
AB  - Consultation between radiologists and referring physicians is part of routine
      medical practice. Nevertheless, a typical picture archiving and communication
      system contains no provision that will allow this critical interaction to occur
      on-line. The authors describe an image viewing system designed for real-time
      interactive consultation over the Internet. The system has two main components:
      an image viewer and a collaboration server. The image viewer connects to the
      collaboration server over an Internet-compatible network. Once the image viewer
      is connected, its display can be synchronized with that of another connected
      image viewer, so that radiologists can point out image findings and diagnoses in
      real time to remotely located physicians. The image viewer can retrieve images
      from any DICOM-compatible archive. In addition to standard image manipulation
      functions, the image viewer contains a new user interface for image annotation.
      Developed specifically for medical imaging, this user interface is activated by
      mouse actions instead of conventional on-screen controls, greatly improving the
      ease with which annotations can be created. The collaboration system is based on
      a simple yet flexible programming interface that can be readily generalized to
      other types of collaborative applications. The system was developed with the Java
      programming language because of Java's integrated support of Internet-compatible
      networking capabilities.

PMID- 12235334
TI  - CT during hepatic arteriography and portography: an illustrative review.
AB  - The combination of computed tomography (CT) during arterial portography (CTAP)
      and CT during hepatic arteriography (CTHA) has been used for evaluation of
      hepatic neoplasms before partial hepatic resection. Focal hepatic lesions that
      can be demonstrated with CTAP and CTHA include regenerative nodules, dysplastic
      nodules, dysplastic nodules with malignant foci, hepatocellular carcinoma,
      cholangiocarcinoma, hemangioma, and metastases. CTAP is considered the most
      sensitive modality for detection of small hepatic lesions, particularly small
      hepatic tumors such as hepatocellular carcinoma and metastatic tumors. CTHA can
      demonstrate not only hypervascular tumors but also hypovascular tumors and can
      help differentiate malignant from benign lesions. However, various types of
      nontumorous hemodynamic changes are frequently encountered at CTAP or CTHA and
      appear as focal lesions that mimic true hepatic lesions. Such hemodynamic changes
      include several types of arterioportal shunts, liver cirrhosis, Budd-Chiari
      syndrome, inflammatory changes, pseudolesions due to an aberrant blood supply,
      and laminar flow in the portal vein. Familiarity with the CTAP and CTHA
      appearances of various hepatic lesions and nontumorous hemodynamic changes allows
      the radiologist to improve the diagnostic accuracy.

PMID- 12235335
TI  - Three-dimensional multi-detector row CT portal venography in the evaluation of
      portosystemic collateral vessels in liver cirrhosis.
AB  - Multi-detector row computed tomography (CT) offers distinct advantages over
      traditional spiral CT. Multi-detector row CT scanners are faster and allow
      thinner collimation than single-detector row spiral CT scanners. The use of multi
      detector row CT combined with postprocessing of the imaging data with a variety
      of three-dimensional reformatting techniques (eg, maximum intensity projection,
      shaded surface display, volume rendering) allows creation of vascular maps whose
      quality equals or exceeds that of maps created at classic angiography for many
      applications. Three-dimensional multi-detector row CT portal venography can help
      determine the extent and location of portosystemic collateral vessels (eg, left
      gastric vein, short gastric vein, esophageal and paraesophageal varices,
      splenorenal and gastrorenal shunts, paraumbilical and abdominal wall veins) in
      patients with liver cirrhosis and is probably the optimal imaging technique in
      this setting.

PMID- 12235336
TI  - Transhepatic portal vein embolization: anatomy, indications, and technical
      considerations.
AB  - Portal vein embolization (PVE) is increasingly being accepted as a useful
      procedure in the preoperative treatment of patients selected for major hepatic
      resection. PVE is performed via either the percutaneous transhepatic or the
      transileocolic route and is usually reserved for patients whose future liver
      remnants are too small to allow resection. It is a safe and effective method for
      inducing selective hepatic hypertrophy of the nondiseased portion of the liver
      and may thereby reduce complications and shorten hospital stays after resection.
      A thorough knowledge of hepatic segmentation and portal venous anatomy is
      essential before performing PVE. In addition, the indications and
      contraindications for PVE, the methods for assessing hepatic lobar hypertrophy,
      the means of determining optimal timing of resection, and the possible
      complications of PVE need to be fully understood before undertaking the
      procedure. Technique may vary among operators, and further research is necessary
      to determine the best embolic agents available and the expected rates of liver
      regeneration for PVE. Nevertheless, as hepatobiliary surgeons become more
      experienced at performing extended hepatic resections, PVE may be requested more
      frequently.

PMID- 12235337
TI  - Transcatheter arterial chemoembolization for hepatocellular carcinoma: anatomic
      and hemodynamic considerations in the hepatic artery and portal vein.
AB  - Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver.
      Although several therapeutic options have been advocated, transcatheter arterial
      chemoembolization (TACE) in particular has been widely performed in the treatment
      of HCC. Still, hepatic arteriography and portography are mandatory for evaluation
      of (a) the resectability and multiplicity of HCCs and (b) the hemodynamic status
      of the portal vein. Thereafter, TACE can be considered as the initial therapeutic
      modality. The possibility of nontarget organ complications during TACE (eg,
      ischemic cholecystitis, splenic infarction, gastrointestinal mucosal lesions,
      pulmonary embolism and infarction, spinal cord injury, ischemic skin lesions)
      should be taken seriously. A thorough understanding of the anatomic variants and
      hemodynamic features of the hepatic artery and portal vein is the first step in
      performing effective and safe TACE for HCC.

PMID- 12235339
TI  - Algorithmic approach to CT diagnosis of the abnormal bowel wall.
AB  - Computed tomography demonstrates intestinal wall abnormalities that can be
      analyzed by categorizing attenuation changes in the intestinal wall and
      transposing morphologic characteristics learned from barium studies. These
      attenuation patterns include white, gray, water halo sign, fat halo sign, and
      black. The white pattern represents avid contrast material enhancement that
      uniformly affects most of the thickened bowel wall. If the bowel wall is enhanced
      to a degree equal to or greater than that of venous opacification in the same
      scan, it should be classified in the white attenuation pattern. Common diagnoses
      with this pattern include idiopathic inflammatory bowel diseases and vascular
      disorders. The gray pattern is defined as a thickened bowel wall with limited
      enhancement whose homogeneous attenuation is comparable with that of enhanced
      muscle. This pattern is used to differentiate between benign and malignant
      disease, but it is the least specific of the patterns and should be combined with
      morphologic observations. The water halo sign indicates stratification within a
      thickened bowel wall that consists of either two or three continuous,
      symmetrically thickened layers. Common diagnoses with this sign include
      idiopathic inflammatory bowel diseases, vascular disorders, infectious diseases,
      and radiation damage. The fat halo sign refers to a three-layered target sign of
      thickened bowel in which the middle or "submucosal" layer has a fatty
      attenuation. Common diagnoses with this sign include Crohn disease in the small
      intestine and idiopathic inflammatory bowel diseases in the colon. Black
      attenuation is the equivalent of pneumatosis, and this pattern is commonly seen
      in ischemia, infection, and trauma.

PMID- 12235341
TI  - Helical CT features of arrhythmogenic right ventricular cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC), also known as
      arrhythmogenic right ventricular dysplasia, is a disorder of the heart muscle of
      unknown origin. It is characterized by electrical instability of the heart as a
      result of replacement of the right ventricular myocardium with fatty or fibrous
      fatty tissue. Dilatation of the right ventricle; fatty tissue in conspicuous
      trabeculae of the right ventricle, especially in the anterior wall, apex, and
      inferior (diaphragmatic) wall; and a scalloped appearance (bulging) of the right
      ventricular wall are characteristic findings at helical computed tomography (CT)
      that may be used to diagnose ARVC. Fatty tissue in the left ventricle and
      ventricular septum is seen relatively frequently in ARVC, and fat in the
      ventricular septum is another useful finding for diagnosis of ARVC with helical
      CT. ARVC is usually diagnosed on the basis of clinical or pathologic findings,
      and electron-beam CT is superior to nongated helical CT in assessment of abnormal
      right ventricular function. However, with knowledge of the characteristic
      findings, standard nongated helical CT can be helpful in diagnosing ARVC.

PMID- 12235342
TI  - Prenatal diagnosis of congenital cardiac anomalies: a practical approach using
      two basic views.
AB  - Structural cardiac anomalies are estimated to occur in 8 of every 1,000 live
      births. Cardiovascular anomalies are frequently associated with other congenital
      anomalies because the heart is among the last organs to develop completely in the
      embryo. The guidelines for routine prenatal evaluation of both the American
      College of Radiology and the American Institute of Ultrasound in Medicine require
      evaluation of the fetal heart. The ultrasonographic (US) view that is most
      commonly used is the four-chamber view, which allows assessment of abnormalities
      involving the atria and the ventricles. However, this view is not adequate for
      demonstrating the outflow tracts of the aorta and pulmonary artery. A base view
      that demonstrates the crossing of the great vessels can be obtained just superior
      to the four-chamber view. Addition of the base view to routine US evaluation with
      the four-chamber view increases not only the sensitivity for detection of cardiac
      anomalies but also the accuracy of diagnosis.

PMID- 12235344
TI  - Anomalies of the distal ureter, bladder, and urethra in children: embryologic,
      radiologic, and pathologic features.
AB  - Congenital anomalies of the lower urinary tract are a significant cause of
      morbidity in infancy. Radiologic investigation is an important source of clinical
      information in lower urinary tract disorders but should not inconvenience the
      patient, expose the patient to unnecessary radiation, or delay surgical
      correction. In pediatric patients with suspected underlying urologic structural
      anomalies, screening ultrasonography is commonly the initial diagnostic study. If
      dilatation of the urinary tract is confirmed, voiding cystourethrography is
      performed to determine the presence of vesicoureteral reflux (VUR) and other
      causes of upper tract dilatation. If VUR is confirmed, follow-up with nuclear
      cystography or echo-enhanced cystosonography may be performed. If VUR is
      excluded, nuclear diuresis renography is the primary test for differentiating
      between obstructed and nonobstructed megaureter. Intravenous urography can be
      used to specifically identify an area of obstruction and to determine the
      presence of duplex collecting systems and a ureterocele. Computed tomography and
      magnetic resonance (MR) imaging are unsuitable for general screening but provide
      superb anatomic detail and added diagnostic specificity. MR imaging is mandatory
      in the evaluation of associated spinal anomalies. MR urography can demonstrate
      ectopic extravesical ureteric insertions, thereby providing a global view of the
      malformation. Familiarity with anomalies of the lower urinary tract is essential
      for correct diagnosis and appropriate management.

PMID- 12235345
TI  - US of neurovascular occlusive disease: interpretive pearls and pitfalls.
AB  - Ultrasonography (US) of the head and neck is a convenient but operator-dependent
      screening tool for detection and diagnosis of neurovascular occlusive disease. In
      US examination of the extracranial carotid arteries, stenosis is most commonly
      graded according to the peak systolic Doppler velocity in the region of maximal
      luminal narrowing rather than according to the percentage of atheromatous plaque
      occupying the lumen. However, the peak systolic velocity is not always reliable
      in estimation of the degree of stenosis. General diagnostic pitfalls include
      technical difficulties with scanning, failure to review the spectral waveform
      patterns, the presence of additional stenotic lesions, and anatomic variants.
      Specific examples of pitfalls include tandem lesions, differentiation of pseudo
      occlusion from true total occlusion, pseudonormalization of velocities in cases
      of very severe stenosis, lesions of the carotid artery origin or aortic valve,
      progression of subclavian steal, underestimation of severe stenosis due to
      heavily calcified plaque, a persistent trigeminal artery, and contralateral
      carotid artery stenosis. Although conventional angiography remains the standard
      of reference for assessment of carotid artery disease, recognition of these
      common sources of error in US can improve the accuracy of this noninvasive test
      in diagnosis of carotid artery occlusion.

PMID- 12235347
TI  - Paget disease of bone.

PMID- 12235346
TI  - Neuronal tumors of the central nervous system: radiologic findings and pathologic
      correlation.
AB  - Pure neuronal and mixed neuronal-glial tumors of the central nervous system are
      uncommon but fascinating because they are less aggressive than the more common
      glial tumors and their prognosis is excellent. Neurologic manifestations are
      varied and include seizures, symptoms of increased intracranial pressure, and
      neurologic deficits according to tumor location. Many neuronal tumors of the
      central nervous system demonstrate characteristic radiologic findings. At
      magnetic resonance (MR) imaging, gangliocytomas demonstrate low signal intensity
      on T1-weighted images, high signal intensity on T2-weighted images, and frequent
      enhancement on gadolinium-enhanced T1-weighted images. Characteristic MR imaging
      findings of Lhermitte-Duclos disease are a nonenhancing mass in a cerebellar
      hemisphere with a striated pattern. Central neurocytomas are typically located in
      the lateral ventricles near the foramen of Monro with a characteristic attachment
      to the septum pellucidum. Ganglioneurocytoma is a rare variant of central
      neurocytoma that is characterized by differentiation toward ganglion cells. In
      ganglioglioma, a well-defined cystic mass with a solid mural nodule is typically
      seen. Extension of enhancement to the leptomeninges is characteristic of
      desmoplastic infantile ganglioglioma and correlates with the firm dural
      attachment of the solid component. Dysembryoplastic neuroepithelial tumor has a
      well-demarcated, multilobulated or gyriform appearance.

PMID- 12235348
TI  - From the archives of the AFIP. Radiologic spectrum of Paget disease of bone and
      its complications with pathologic correlation.
AB  - Paget disease of bone is a common disorder affecting approximately 3%-4% of the
      population over 40 years of age. The pathologic abnormality in Paget disease is
      excessive and abnormal remodeling of bone. Three pathologic phases have been
      described: the lytic phase (incipient-active), in which osteoclasts predominate;
      the mixed phase (active), in which osteoblasts cause repair superimposed on the
      resorption; and the blastic phase (late-inactive) in which osteoblasts
      predominate. Radiographic appearance of Paget disease reflects these pathologic
      changes and is often characteristic. Initially, there is osteolysis, particularly
      affecting the skull (osteoporosis circumscripta) and subchondral long bones, with
      subsequent development of trabecular and cortical thickening and enlargement of
      bone in the mixed phase of the disease. Finally, areas of sclerosis may develop
      in the blastic phase. Frequent sites of involvement include the skull (25%-65% of
      cases), spine (30%-75%), pelvis (30%-75%), and proximal long bones (25%-30%).
      Bone scintigraphy typically demonstrates marked increased uptake of radionuclide
      in all phases of Paget disease. Computed tomography and magnetic resonance
      imaging often show changes similar to those seen radiographically in
      noncomplicated Paget disease with maintenance of yellow marrow. Complications of
      Paget disease include the effects of osseous weakening (deformity and fracture),
      arthritis, neurologic symptoms, and neoplastic involvement. Sarcomatous
      transformation is the most feared complication, occurring in approximately 1% of
      cases, and is seen on images as focal bone destruction extending through the
      cortex with an associated soft-tissue mass. Recognition of the radiologic
      spectrum of the appearances of Paget disease usually allows prospective diagnosis
      and differentiation of its associated complications, which helps guide therapy
      and improve patient management.

PMID- 12235349
TI  - Best cases from the AFIP. Ileocecal enteric duplication cyst: radiologic
      pathologic correlation.

PMID- 12235350
TI  - Special focus session. MR arthrography.
AB  - Direct magnetic resonance (MR) arthrography with injection of saline solution or
      diluted gadolinium can be useful for evaluating certain pathologic conditions in
      the joints. It is most helpful for outlining labral-ligamentous abnormalities in
      the shoulder and distinguishing partial-thickness from full-thickness tears in
      the rotator cuff, demonstrating labral tears in the hip, showing partial- and
      full-thickness tears of the collateral ligament of the elbow and delineating
      bands in the elbow, identifying residual or recurrent tears in the knee following
      meniscectomy, increasing the certainty of perforations of the ligaments and
      triangular fibrocartilage in the wrist, correctly identifying ligament tears in
      the ankle and increasing the sensitivity for ankle impingement syndromes,
      assessing the stability of osteochondral lesions in the articular surface of
      joints, and delineating loose bodies in joints. Indirect MR arthrography with
      intravenous administration of diluted gadolinium may be performed when direct
      arthrography is inconvenient or not logistically feasible. Although indirect MR
      arthrography has some disadvantages vis-a-vis direct MR arthrography, it does not
      require fluoroscopic guidance or joint injection and it is superior to
      conventional MR imaging in delineating structures when there is minimal joint
      fluid. In addition, vascularized or inflamed tissue will enhance with this
      method. Indirect MR arthrography can be used to rule in or diagnose abnormalities
      and to exclude abnormalities.

PMID- 12235351
TI  - AAPM/RSNA physics tutorial for residents: topics in CT. Image processing in CT.
AB  - Several image-processing methods for computed tomographic (CT) examinations are
      currently being used in clinical radiology departments. Image processing involves
      operations such as reformatting of original CT images, volume-rendered displays,
      surface-rendered displays, and physiologic imaging analysis. The reformatting
      process does not alter the CT voxels in any way; instead it uses them in off-axis
      views and displays the images produced from the original reconstruction process
      in an orientation other than how they were originally generated. Sagittal,
      coronal, oblique, and curved reformatting are standard reformatting methods.
      Other reformatting techniques include maximum-intensity projection, minimum
      intensity projection, and variable thickness viewing. Volume and surface
      rendering are two different methods for reformatting axial images into three
      dimensional views. CT perfusion allows the measurement of physiologic parameters
      over time. Additional postprocessing efforts can potentially add value to the
      patients and their outcomes, as can be seen in the cases that illustrate this
      article.

PMID- 12235353
TI  - Principal component analysis for content-based image retrieval.
AB  - Most picture archiving and communication systems provide image search
      capabilities that support queries based on patient demographics and study
      descriptions. In a preliminary study, principal component analysis was used to
      represent and retrieve images on the basis of content. Principal component
      analysis reduces the dimensionality of the search to a basis set of prototype
      images that best describes the images. Each image is described by its projection
      on the basis set; a match to a query image is determined by comparing its
      projection vector on the basis set with that of the images in the database. The
      training image database consisted of 100 axial brain images from a three
      dimensional T1-weighted magnetic resonance imaging study. The algorithm was
      evaluated by using 96 axial images from eight patients. Image retrieval was
      considered accurate if the automated algorithm returned the match section to
      within 3 mm of an expert-selected section; the retrieval accuracy was 83% when
      the images were preprocessed for uniformity in intensity and geometry. Principal
      component analysis can be applied to content-based retrieval of medical images.
      The algorithm is designed to be part of an automated image selection module that
      filters relevant images from an imaging study.

PMID- 12235354
TI  - Image interpretation session. Sunday, December 1, 2002.

PMID- 12235356
TI  - Nanocrystal targeting in vivo.
AB  - Inorganic nanostructures that interface with biological systems have recently
      attracted widespread interest in biology and medicine. Nanoparticles are thought
      to have potential as novel intravascular probes for both diagnostic (e.g.,
      imaging) and therapeutic purposes (e.g., drug delivery). Critical issues for
      successful nanoparticle delivery include the ability to target specific tissues
      and cell types and escape from the biological particulate filter known as the
      reticuloendothelial system. We set out to explore the feasibility of in vivo
      targeting by using semiconductor quantum dots (qdots). Qdots are small (<10 nm)
      inorganic nanocrystals that possess unique luminescent properties; their
      fluorescence emission is stable and tuned by varying the particle size or
      composition. We show that ZnS-capped CdSe qdots coated with a lung-targeting
      peptide accumulate in the lungs of mice after i.v. injection, whereas two other
      peptides specifically direct qdots to blood vessels or lymphatic vessels in
      tumors. We also show that adding polyethylene glycol to the qdot coating prevents
      nonselective accumulation of qdots in reticuloendothelial tissues. These results
      encourage the construction of more complex nanostructures with capabilities such
      as disease sensing and drug delivery.

PMID- 12235357
TI  - Significance and statistical errors in the analysis of DNA microarray data.
AB  - DNA microarrays are important devices for high throughput measurements of gene
      expression, but no rational foundation has been established for understanding the
      sources of within-chip statistical error. We designed a specialized chip and
      protocol to investigate the distribution and magnitude of within-chip errors and
      discovered that, as expected from theoretical expectations, measurement errors
      follow a Lorentzian-like distribution, which explains the widely observed but
      unexplained ill-reproducibility in microarray data. Using this specially designed
      chip, we examined a data set of repeated measurements to extract estimates of the
      distribution and magnitude of statistical errors in DNA microarray measurements.
      Using the common "ratio of medians" method, we find that the measurements follow
      a Lorentzian-like distribution, which is problematic for subsequent analysis. We
      show that a method of analysis dubbed "median of ratios" yields a more Gaussian
      like distribution of errors. Finally, we show that the bootstrap algorithm can be
      used to extract the best estimates of the error in the measurement. Quantifying
      the statistical error in such measurements has important applications for
      estimating significance levels, clustering algorithms, and process optimization.

PMID- 12235355
TI  - Unfolding of quadruplex structure in the G-rich strand of the minisatellite
      repeat by the binding protein UP1.
AB  - The mouse hypervariable minisatellite (MN) Pc-1 consists of tandem repeats of
      d(GGCAG) and flanked sequences. We have previously demonstrated that single
      stranded d(GGCAG)(n) folds into the intramolecular folded-back quadruplex
      structure under physiological conditions. Because DNA polymerase progression in
      vitro is blocked at the repeat, the characteristic intramolecular quadruplex
      structure of the repeat, at least in part, could be responsible for the
      hypermutable feature of Pc-1 and other MNs with similar repetitive units. On the
      other hand, we have isolated six MN Pc-1 binding proteins (MNBPs) from nuclear
      extracts of NIH 3T3 cells. Here, we describe one of those MNBPs, MNBP-B, that
      binds to the single-stranded d(GGCAG)(n). Amino acid sequences of seven
      proteolytic peptide fragments of MNBP-B were determined, and the cDNA clones were
      isolated. MNBP-B was proven identical to the single-stranded DNA-binding protein,
      UP1. Recombinant UP1 bound to single-stranded d(GGCAG)(n) and other G-rich
      repetitive sequences, such as d(GTCAGG)(n) and d(GTTAGG)(n). In addition, UP1 was
      demonstrated by CD spectrum analysis to unfold the intramolecular quadruplex
      structure of d(GGCAG)(5) and d(TTAGGG)(4) and to abrogate the arrest of DNA
      synthesis at the d(GGG)(n) site. This ability of UP1 suggests that unfolding of
      quadruplex DNA is required for DNA synthesis processes.

PMID- 12235358
TI  - One O-linked sugar can affect the coil-to-beta structural transition of the prion
      peptide.
AB  - It has been known that the structural transition from PrP(C) to PrP(Sc) leads to
      the prion formation. This putative conformational change challenges the central
      dogma of the protein folding theory-"one sequence, one structure." Generally,
      scientists believe that there must be either a posttranslational modification or
      environmental factors involved in this event. However, all of the efforts to
      solve the mystery of the PrP(C) to PrP(Sc) transition have ended in vain so far.
      Here we provide evidence linking O-linked glycosylation to the structural
      transition based on prion peptide studies. We find that the O-linked alpha-GalNAc
      at Ser-135 suppresses the formation of amyloid fibril formation of the prion
      peptide at physiological salt concentrations, whereas the peptide with the same
      sugar at Ser-132 shows the opposite effect. Moreover, this effect is sugar
      specific. Replacing alpha-GalNAc with beta-GlcNAc does not yield the same effect.

PMID- 12235360
TI  - Familial hemiplegic migraine mutations increase Ca(2+) influx through single
      human CaV2.1 channels and decrease maximal CaV2.1 current density in neurons.
AB  - Insights into the pathogenesis of migraine with aura may be gained from a study
      of human Ca(V)2.1 channels containing mutations linked to familial hemiplegic
      migraine (FHM). Here, we extend the previous single-channel analysis to human
      Ca(V)2.1 channels containing mutation V1457L. This mutation increased the channel
      open probability by shifting its activation to more negative voltages and reduced
      both the unitary conductance and the density of functional channels in the
      membrane. To investigate the possibility of changes in Ca(V)2.1 function common
      to all FHM mutations, we calculated the product of single-channel current and
      open probability as a measure of Ca(2+) influx through single Ca(V)2.1 channels.
      All five FHM mutants analyzed showed a single-channel Ca(2+) influx larger than
      wild type in a broad voltage range around the threshold of activation. We also
      expressed the FHM mutants in cerebellar granule cells from Ca(V)2.1alpha(1)-/-
      mice rather than HEK293 cells. The FHM mutations invariably led to a decrease of
      the maximal Ca(V)2.1 current density in neurons. Current densities were similar
      to wild type at lower voltages because of the negatively shifted activation of
      FHM mutants. Our data show that mutational changes of functional channel
      densities can be different in different cell types, and they uncover two
      functional effects common to all FHM mutations analyzed: increase of single
      channel Ca(2+) influx and decrease of maximal Ca(V)2.1 current density in
      neurons. We discuss the relevance of these findings for the pathogenesis of
      migraine with aura.

PMID- 12235359
TI  - Fast synaptic inhibition promotes synchronized gamma oscillations in hippocampal
      interneuron networks.
AB  - Networks of GABAergic interneurons are of critical importance for the generation
      of gamma frequency oscillations in the brain. To examine the underlying synaptic
      mechanisms, we made paired recordings from "basket cells" (BCs) in different
      subfields of hippocampal slices, using transgenic mice that express enhanced
      green fluorescent protein (EGFP) under the control of the parvalbumin promoter.
      Unitary inhibitory postsynaptic currents (IPSCs) showed large amplitude and fast
      time course with mean amplitude-weighted decay time constants of 2.5, 1.2, and
      1.8 ms in the dentate gyrus, and the cornu ammonis area 3 (CA3) and 1 (CA1),
      respectively (33-34 degrees C). The decay of unitary IPSCs at BC-BC synapses was
      significantly faster than that at BC-principal cell synapses, indicating target
      cell-specific differences in IPSC kinetics. In addition, electrical coupling was
      found in a subset of BC-BC pairs. To examine whether an interneuron network with
      fast inhibitory synapses can act as a gamma frequency oscillator, we developed an
      interneuron network model based on experimentally determined properties. In
      comparison to previous interneuron network models, our model was able to generate
      oscillatory activity with higher coherence over a broad range of frequencies (20
      110 Hz). In this model, high coherence and flexibility in frequency control
      emerge from the combination of synaptic properties, network structure, and
      electrical coupling.

PMID- 12235361
TI  - Topical colchicine selection of keratinocytes transduced with the multidrug
      resistance gene (MDR1) can sustain and enhance transgene expression in vivo.
AB  - For skin gene therapy, achieving prolonged high-level gene expression in a
      significant percentage of keratinocytes (KC) is difficult because we cannot
      selectively target KC stem cells. We now demonstrate that topical colchicine
      treatment can be used to select, in vivo, KC progenitor cells transduced with the
      multidrug resistance gene (MDR1). When human skin equivalents containing MDR1
      transduced KC were grafted onto immunocompromised mice, topical colchicine
      treatments significantly increased (7-fold) the percentage of KC expressing MDR1,
      compared to vehicle-treated controls, for up to 24 wk. Topical colchicine
      treatment also significantly enhanced the amount of MDR1 protein expressed in
      individual KC. Furthermore, quantitative real-time PCR analysis of MDR1 transgene
      copy number demonstrates that topical colchicine treatment selects and enriches
      for KC progenitor cells in the skin that contain and express MDR1. For clinical
      skin gene therapy applications, this in vivo selection approach promises to
      enhance both the duration and expression level of a desired therapeutic gene in
      KC, by linking its expression to the MDR1 selectable marker gene.

PMID- 12235362
TI  - Antiviral and antitumor peptides from insects.
AB  - Insects can rapidly clear microbial infections by producing a variety of immune
      induced molecules including antibacterial and/or antifungal
      peptides/polypeptides. In this report, we present the isolation, structural
      characterization, and biological properties of two variants of a group of
      bioactive, slightly cationic peptides, referred to as alloferons. Two peptides
      were isolated from the blood of an experimentally infected insect, the blow fly
      Calliphora vicina (Diptera), with the following amino acid sequences:
      HGVSGHGQHGVHG (alloferon 1) and GVSGHGQHGVHG (alloferon 2). Although these
      peptides have no clear homologies with known immune response modifiers, protein
      database searches established some structural similarities with proteins
      containing amino acid stretches similar to alloferon. In vitro experiments reveal
      that the synthetic version of alloferon has stimulatory activities on natural
      killer lymphocytes, whereas in vivo trials indicate induction of IFN production
      in mice after treatments with synthetic alloferon. Additional in vivo experiments
      in mice indicate that alloferon has antiviral and antitumoral capabilities. Taken
      together, these results suggest that this peptide, which has immunomodulatory
      properties, may have therapeutic capacities. The fact that insects may produce
      cytokine-like materials modulating basic mechanisms for human immunity suggests a
      source of anti-infection and antitumoral biopharmaceuticals.

PMID- 12235363
TI  - Experimental autoimmune encephalomyelitis mobilizes neural progenitors from the
      subventricular zone to undergo oligodendrogenesis in adult mice.
AB  - The destiny of the mitotically active cells of the subventricular zone (SVZ) in
      adult rodents is to migrate to the olfactory bulb, where they contribute to the
      replacement of granular and periglomerular neurons. However, these adult neural
      progenitors also can be mobilized in periventricular white matter and triggered
      to differentiate into astrocytes and oligodendrocytes in response to lysolecithin
      induced demyelination. To mimic the environmental conditions of multiple
      sclerosis, we assessed the proliferation, migration, and differentiation
      potential of adult SVZ progenitor cells in response to experimental autoimmune
      encephalomyelitis (EAE) in mice. Inflammation and demyelination were observed in
      all mouse brains after EAE induction. EAE induced cell proliferation throughout
      the brain and especially within the lesions. Proliferating cells were neural
      progenitors, astrocytes, and oligodendrocyte precursors. EAE enhanced the
      migration of SVZ-derived neural progenitors to the olfactory bulb and triggered
      their mobilization in the periventricular white matter. The mobilized cells gave
      rise to neurons, astrocytes, and oligodendrocytes in the olfactory bulb but
      essentially to astrocytes and oligodendrocytes in the lesioned white matter. Our
      data indicate that the adult mouse SVZ is a source of newly generated
      oligodendrocytes and thus may contribute, along with oligodendrocyte precursors,
      to the replacement of oligodendrocytes in inflammatory demyelinating diseases of
      the central nervous system such as multiple sclerosis.

PMID- 12235364
TI  - Food-web structure and network theory: The role of connectance and size.
AB  - Networks from a wide range of physical, biological, and social systems have been
      recently described as "small-world" and "scale-free." However, studies disagree
      whether ecological networks called food webs possess the characteristic path
      lengths, clustering coefficients, and degree distributions required for
      membership in these classes of networks. Our analysis suggests that the
      disagreements are based on selective use of relatively few food webs, as well as
      analytical decisions that obscure important variability in the data. We analyze a
      broad range of 16 high-quality food webs, with 25-172 nodes, from a variety of
      aquatic and terrestrial ecosystems. Food webs generally have much higher
      complexity, measured as connectance (the fraction of all possible links that are
      realized in a network), and much smaller size than other networks studied, which
      have important implications for network topology. Our results resolve prior
      conflicts by demonstrating that although some food webs have small-world and
      scale-free structure, most do not if they exceed a relatively low level of
      connectance. Although food-web degree distributions do not display a universal
      functional form, observed distributions are systematically related to network
      connectance and size. Also, although food webs often lack small-world structure
      because of low clustering, we identify a continuum of real-world networks
      including food webs whose ratios of observed to random clustering coefficients
      increase as a power-law function of network size over 7 orders of magnitude.
      Although food webs are generally not small-world, scale-free networks, food-web
      topology is consistent with patterns found within those classes of networks.

PMID- 12235365
TI  - The membrane trafficking protein calpactin forms a complex with bluetongue virus
      protein NS3 and mediates virus release.
AB  - Bluetongue virus, an arbovirus of the Orbivirus genus, infects and replicates in
      both insect and mammalian cells. However, the cytopathic effect (cpe) on each
      host is very different. Mammalian cells show substantial cpe, most likely a
      result of the mechanism of virus release, whereas insect cells show little cpe
      and appear to release virus without cell lysis. Expression analysis of each
      infected cell type shows one protein, the nonstructural (NS) protein NS3, to be
      differentially expressed in the different cell types, suggesting it may act in
      the virus egress pathway. The molecular basis of such an interaction, however,
      has never been clear. Here, by using yeast two-hybrid analysis, we show that NS3
      interacts with a cellular protein p11 (calpactin light chain), part of the
      annexin II complex that is involved in exocytosis. We map the NS3 region of
      interaction with p11 to a 13-residue peptide found at the N terminus of the
      protein and show it effectively competes with p36 (annexin II heavy chain) for
      p11 ligand binding. Further, we show that the C-terminal domain of NS3 interacts
      with VP2, the outermost protein of the fully assembled virus particle, suggesting
      that NS3 forms a bridging molecule that draws assembled virus into contact with
      the cellular export machinery. Our data describe the first host protein
      involvement in orbivirus egress and provide new insights into understanding
      arbovirus interactions with their hosts.

PMID- 12235367
TI  - Two degrees of separation in complex food webs.
AB  - Feeding relationships can cause invasions, extirpations, and population
      fluctuations of a species to dramatically affect other species within a variety
      of natural habitats. Empirical evidence suggests that such strong effects rarely
      propagate through food webs more than three links away from the initial
      perturbation. However, the size of these spheres of potential influence within
      complex communities is generally unknown. Here, we show for that species within
      large communities from a variety of aquatic and terrestrial ecosystems are on
      average two links apart, with >95% of species typically within three links of
      each other. Species are drawn even closer as network complexity and, more
      unexpectedly, species richness increase. Our findings are based on seven of the
      largest and most complex food webs available as well as a food-web model that
      extends the generality of the empirical results. These results indicate that the
      dynamics of species within ecosystems may be more highly interconnected and that
      biodiversity loss and species invasions may affect more species than previously
      thought.

PMID- 12235366
TI  - Abnormal gene expression in cloned mice derived from embryonic stem cell and
      cumulus cell nuclei.
AB  - To assess the extent of abnormal gene expression in clones, we assessed global
      gene expression by microarray analysis on RNA from the placentas and livers of
      neonatal cloned mice derived by nuclear transfer (NT) from both cultured
      embryonic stem cells and freshly isolated cumulus cells. Direct comparison of
      gene expression profiles of more than 10,000 genes showed that for both donor
      cell types approximately 4% of the expressed genes in the NT placentas differed
      dramatically in expression levels from those in controls and that the majority of
      abnormally expressed genes were common to both types of clones. Importantly,
      however, the expression of a smaller set of genes differed between the embryonic
      stem cell- and cumulus cell-derived clones. The livers of the cloned mice also
      showed abnormal gene expression, although to a lesser extent, and with a
      different set of affected genes, than seen in the placentas. Our results
      demonstrate frequent abnormal gene expression in clones, in which most expression
      abnormalities appear common to the NT procedure whereas others appear to reflect
      the particular donor nucleus.

PMID- 12235368
TI  - Acceleration of genomic evolution caused by enhanced mutation rate in
      endocellular symbionts.
AB  - Endosymbionts, which are widely observed in nature, have undergone reductive
      genome evolution because of their long-term intracellular lifestyle. Here we
      compared the complete genome sequences of two different endosymbionts, Buchnera
      and a protist mitochondrion, with their close relatives to study the evolutionary
      rates of functional genes in endosymbionts. The results indicate that the rate of
      amino acid substitution is two times higher in symbionts than in their relatives.
      This rate increase was observed uniformly among different functional classes of
      genes, although strong purifying selection may have counterbalanced the rate
      increase in a few cases. Our data suggest that, contrary to current views,
      neither the Muller's ratchet effect nor the slightly deleterious mutation theory
      sufficiently accounts for the elevated evolutionary rate. Rather, the elevated
      evolutionary rate appears to be mainly due to enhanced mutation rate, although
      the possibility of relaxation of purifying selection cannot be ruled out.

PMID- 12235369
TI  - Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness,
      and a prelamin A processing defect.
AB  - Zmpste24 is an integral membrane metalloproteinase of the endoplasmic reticulum.
      Biochemical studies of tissues from Zmpste24-deficient mice (Zmpste24(-/-)) have
      indicated a role for Zmpste24 in the processing of CAAX-type prenylated proteins.
      Here, we report the pathologic consequences of Zmpste24 deficiency in mice.
      Zmpste24(-/-) mice gain weight slowly, appear malnourished, and exhibit
      progressive hair loss. The most striking pathologic phenotype is multiple
      spontaneous bone fractures-akin to those occurring in mouse models of
      osteogenesis imperfecta. Cortical and trabecular bone volumes are significantly
      reduced in Zmpste24(-/-) mice. Zmpste24(-/-) mice also manifested muscle weakness
      in the lower and upper extremities, resembling mice lacking the farnesylated CAAX
      protein prelamin A. Prelamin A processing was defective both in fibroblasts
      lacking Zmpste24 and in fibroblasts lacking the CAAX carboxyl methyltransferase
      Icmt but was normal in fibroblasts lacking the CAAX endoprotease Rce1. Muscle
      weakness in Zmpste24(-/-) mice can be reasonably ascribed to defective processing
      of prelamin A, but the brittle bone phenotype suggests a broader role for
      Zmpste24 in mammalian biology.

PMID- 12235370
TI  - Insect feeding mobilizes a unique plant defense protease that disrupts the
      peritrophic matrix of caterpillars.
AB  - Plants frequently respond to herbivorous insect attack by synthesizing defense
      proteins that deter insect feeding and prevent additional herbivory. Maize (Zea
      mays L.) lines, resistant to feeding by a number of lepidopteran species, rapidly
      mobilize a unique 33-kDa cysteine protease in response to caterpillar feeding.
      The accumulation of the 33-kDa cysteine protease in the maize mid-whorl was
      correlated with a significant reduction in caterpillar growth that resulted from
      impaired nutrient utilization. Black Mexican Sweetcorn callus transformed with
      mir1, the gene encoding the 33-kDa cysteine protease, expressed the protease and
      growth of caterpillars reared on the transgenic callus was reduced 60-80%.
      Scanning electron microscopy was used to examine the effect of plant material
      expressing the 33-kDa cysteine protease on the structure of the caterpillar
      peritrophic matrix. Because the peritrophic matrix surrounds the food bolus,
      assists in digestive processes, and protects the caterpillar midgut from physical
      and chemical damage, disruption of peritrophic matrix may reduce caterpillar
      growth. The results indicated that the peritrophic matrix was severely damaged
      when caterpillars fed on resistant maize plants or transgenic Black Mexican
      Sweetcorn. The accumulation of the 33-kDa cysteine protease in response to
      caterpillar feeding, and its ability to damage the insect peritrophic matrix,
      represents an unusual host-plant resistance mechanism that may have applications
      in agricultural biotechnology.

PMID- 12235371
TI  - Lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 inhibit peroxynitrite
      formation, NF-kappa B and AP-1 activation, and IL-8 gene expression in human
      leukocytes.
AB  - Lipoxin A(4) (LXA(4)) and aspirin-triggered 15-epi-LXA(4) (ATL) are emerging as
      endogenous braking signals for neutrophil-mediated tissue injury. Recent studies
      indicate that peroxynitrite (ONOO(-)) may function as an intracellular signal for
      the production of IL-8, a potent proinflammatory cytokine in human leukocytes. In
      this study, we evaluated the impact of the metabolically stable analogues of
      LXA(4)/ATL on lipopolysaccharide (LPS)-induced ONOO(-) formation and ONOO(-)
      mediated IL-8 gene expression in human leukocytes. At nanomolar concentrations,
      LXA(4) analogues markedly reduced LPS-stimulated superoxide formation, evoked
      increases in intracellular diamino-fluorescein fluorescence (an indicator of NO
      formation), and consequently reduced ONOO(-) formation in isolated neutrophils,
      as well as in neutrophils, monocytes, and lymphocytes, in whole blood. LXA(4)/ATL
      analogues attenuated nuclear accumulation of activator protein-1 and nuclear
      factor-kappaB in both polymorphonuclear and mononuclear leukocytes and inhibited
      IL-8 mRNA expression and IL-8 release by 50-65% in response to LPS. The LXA(4)
      inhibitory responses were concentration dependent and were not shared by 15-deoxy
      LXA(4). None of the LXA(4) analogues studied affected neutrophil survival, nor
      reversed the apoptosis delaying action of LPS in neutrophils. In addition, LXA(4)
      analogues had no significant effect on exogenous ONOO(-)-induced IL-8 gene and
      protein expression. These findings suggest that by attenuating ONOO(-) formation,
      LXA(4) and ATL can oppose ONOO(-) signaling in leukocytes and provide a rationale
      for using stable synthetic analogues as antiinflammatory compounds in vivo.

PMID- 12235372
TI  - Low atmospheric CO(2) levels during the Permo- Carboniferous glaciation inferred
      from fossil lycopsids.
AB  - Earth history was punctuated during the Permo-Carboniferous [300-250 million
      years (Myr) ago] by the longest and most severe glaciation of the entire
      Phanerozoic Eon. But significant uncertainty surrounds the concentration of CO(2)
      in the atmosphere through this time interval and therefore its role in the
      evolution of this major prePleistocene glaciation. Here, I derive 24 Late
      Paleozoic CO(2) estimates from the fossil cuticle record of arborsecent lycopsids
      of the equatorial Carboniferous and Permian swamp communities. Quantitative
      calibration of Late Carboniferous (330-300 Myr ago) and Permian (270-260 Myr ago)
      lycopsid stomatal indices yield average atmospheric CO(2) concentrations of 344
      ppm and 313 ppm, respectively. The reconstructions show a high degree of self
      consistency and a degree of precision an order of magnitude greater than other
      approaches. Low CO(2) levels during the Permo-Carboniferous glaciation are in
      agreement with glaciological evidence for the presence of continental ice and
      coupled models of climate and ice-sheet growth on Pangea. Moreover, the Permian
      data indicate atmospheric CO(2) levels were low 260 Myr ago, by which time
      continental deglaciation was already underway. Positive biotic feedbacks on
      climate, and geotectonic events, therefore are implicated as mechanisms
      underlying deglaciation.

PMID- 12235373
TI  - Synapse formation is associated with memory storage in the cerebellum.
AB  - The idea that memory is encoded by means of synaptic growth is not new. However,
      this idea has been difficult to demonstrate in the mammalian brain because of
      both the complexity of mammalian behavior and the neural circuitry by which it is
      supported. Here we examine how eyeblink classical conditioning affects synapse
      number within the cerebellum; the brain region essential for long-term retention
      of the conditioned response. Results showed eyeblink-conditioned rats to have
      significantly more synapses per neuron within the cerebellar interpositus nucleus
      than both explicitly unpaired and untrained controls. Further analysis showed
      that the increase was caused by the addition of excitatory rather than inhibitory
      synapses. Thus, development of the conditioned eyeblink response is associated
      with a strengthening of inputs from precerebellar nuclei rather than from
      cerebellar cortex. These results demonstrate that the modifications of specific
      neural pathways by means of synaptogenesis contributes to formation of a specific
      memory within the mammalian brain.

PMID- 12235374
TI  - T cells from the tumor microenvironment of patients with progressive myeloma can
      generate strong, tumor-specific cytolytic responses to autologous, tumor-loaded
      dendritic cells.
AB  - Most untreated cancer patients develop progressive tumors. We tested the capacity
      of T lymphocytes from patients with clinically progressive, multiple myeloma to
      develop killer function against fresh autologous tumor. In this malignancy, it is
      feasible to reproducibly evaluate freshly isolated tumor cells and T cells from
      the marrow tumor environment. When we did this with seven consecutive patients,
      with all clinical stages of disease, we did not detect reactivity to autologous
      cancer cells. However, both cytolytic and IFN-gamma-producing responses to
      autologous myeloma were generated in six of seven patients after stimulation ex
      vivo with dendritic cells that had processed autologous tumor cells. The
      antitumor effectors recognized fresh autologous tumor but not nontumor cells in
      the bone marrow, myeloma cell lines, dendritic cells loaded with tumor-derived
      Ig, or allogeneic tumor. Importantly, these CD8(+) effectors developed with
      similar efficiency by using T cells from both the blood and the bone marrow tumor
      environment. Therefore, even in the setting of clinical tumor progression, the
      tumor bed of myeloma patients contains T cells that can be activated readily by
      dendritic cells to kill primary autologous tumor.

PMID- 12235375
TI  - Expression of the human DNA glycosylase hSMUG1 in Trypanosoma brucei causes DNA
      damage and interferes with J biosynthesis.
AB  - In kinetoplastid flagellates such as Trypanosoma brucei, a small percentage of
      the thymine residues in the nuclear DNA is replaced by the modified base beta-D
      glucosyl-hydroxymethyluracil (J), mostly in repetitive sequences like the
      telomeric GGGTTA repeats. In addition, traces of 5-hydroxymethyluracil (HOMeUra)
      are present. Previous work has suggested that J is synthesised in two steps via
      HOMedU as an intermediate, but as J synthesising enzymes have not yet been
      identified, the biosynthetic pathway remains unclear. To test a model in which
      HOMeUra functions as a precursor of J, we introduced an inducible gene for the
      human DNA glycosylase hSMUG1 into bloodstream form T.brucei. In higher eukaryotes
      SMUG1 excises HOMeUra as part of the base excision repair system. We show that
      expression of the gene in T.brucei leads to massive DNA damage in J-modified
      sequences and results in cell cycle arrest and, eventually, death. hSMUG1 also
      reduces the J content of the trypanosome DNA. This work supports the idea that
      HOMeUra is a precursor of J, freely accessible to a DNA glycosylase.

PMID- 12235377
TI  - Interaction of the ocr gene 0.3 protein of bacteriophage T7 with EcoKI
      restriction/modification enzyme.
AB  - The ocr protein, the product of gene 0.3 of bacteriophage T7, is a structural
      mimic of the phosphate backbone of B-form DNA. In total it mimics 22 phosphate
      groups over approximately 24 bp of DNA. This mimicry allows it to block DNA
      binding by type I DNA restriction enzymes and to inhibit these enzymes. We have
      determined that multiple ocr dimers can bind stoichiometrically to the archetypal
      type I enzyme, EcoKI. One dimer binds to the core methyltransferase and two to
      the complete bifunctional restriction and modification enzyme. Ocr can also bind
      to the component subunits of EcoKI. Binding affinity to the methyltransferase
      core is extremely strong with a large favourable enthalpy change and an
      unfavourable entropy change. This strong interaction prevents the dissociation of
      the methyltransferase which occurs upon dilution of the enzyme. This
      stabilisation arises because the interaction appears to involve virtually the
      entire surface area of ocr and leads to the enzyme completely wrapping around
      ocr.

PMID- 12235376
TI  - Genome sequence of Oceanobacillus iheyensis isolated from the Iheya Ridge and its
      unexpected adaptive capabilities to extreme environments.
AB  - Oceanobacillus iheyensis HTE831 is an alkaliphilic and extremely halotolerant
      Bacillus-related species isolated from deep-sea sediment. We present here the
      complete genome sequence of HTE831 along with analyses of genes required for
      adaptation to highly alkaline and saline environments. The genome consists of 3.6
      Mb, encoding many proteins potentially associated with roles in regulation of
      intracellular osmotic pressure and pH homeostasis. The candidate genes involved
      in alkaliphily were determined based on comparative analysis with three Bacillus
      species and two other Gram-positive species. Comparison with the genomes of other
      major Gram-positive bacterial species suggests that the backbone of the genus
      Bacillus is composed of approximately 350 genes. This second genome sequence of
      an alkaliphilic Bacillus-related species will be useful in understanding life in
      highly alkaline environments and microbial diversity within the ubiquitous
      bacilli.

PMID- 12235378
TI  - Micro-processing events in mRNAs identified by DHPLC analysis.
AB  - Post-transcriptional processes such as alternative splicing and RNA editing have
      a huge impact on the diversity of the proteome. Detecting alternatively spliced
      transcripts is difficult when they are rare. In addition, edited transcripts
      often differ from the genomic sequence by only a few nucleotides. Denaturing high
      performance liquid chromatography (DHPLC) is routinely used for single nucleotide
      polymorphism detection and we used this method to detect alternatively spliced or
      edited transcripts. As the sites of RNA editing appear to be conserved within
      gene families, we investigated whether editing sites are conserved in the murine
      homologue of the Drosophila cacophony transcript encoding the alpha1 subunit of a
      voltage-gated calcium channel that is edited at 10 independent positions.
      Although DHPLC analysis detects RNA editing at as low as 3% in control
      transcripts, no evidence of RNA editing was found in the analysed murine
      transcript. However an alternative exon was identified at the 3' end of the mouse
      Cacna1alpha transcript and an alternative micro-exon encoding only two amino
      acids (NP) was found in the extracellular loop before the IVS4 helix in the same
      transcript. In the homologous Drosophila transcript a micro-exon also encoding
      two amino acids was found at the same position before the IVS4 helix.

PMID- 12235379
TI  - G4 DNA unwinding by BLM and Sgs1p: substrate specificity and substrate-specific
      inhibition.
AB  - To understand the specific genetic instabilities associated with deficiencies in
      RecQ family helicases, we have studied the substrate preferences of two closely
      related members of this family, human BLM and Saccharomyces cerevisiae Sgs1p.
      Here we show that both BLM and Sgs1p preferentially unwind G4 DNA relative to
      Holliday junction substrates, and that substrate preference reflects binding
      affinity and maps to the conserved central helicase domain. We identify the
      porphyrin N-methyl mesoporphyrin IX (NMM) as a specific inhibitor of G4 DNA
      unwinding, and show that in the presence of NMM the helicase becomes trapped on
      the NMM-G4 DNA complex, consuming ATP but unable to unwind or dissociate. These
      results suggest that BLM and Sgs1p function proactively in replication to remove
      G4 DNA structures which would otherwise present obstacles to fork progression,
      rather than by promoting recombination to restart a fork that has stalled.

PMID- 12235380
TI  - High resolution crystal structure of domain I of the Saccharomyces cerevisiae
      homing endonuclease PI-SceI.
AB  - The homing endonuclease PI-SceI from Saccharo myces cerevisiae consists of two
      domains. The protein splicing domain I catalyzes the excision of the mature
      endonuclease (intein) from a precursor protein and the religation of the flanking
      amino acid sequences (exteins) to a functional protein. Furthermore, domain I is
      involved in binding and recognition of the specific DNA substrate. Domain II of
      PI-SceI, the endonuclease domain, which is structurally homologous to other
      homing endonucleases from the LAGLIDADG family, harbors the endonucleolytic
      center of PI-SceI, which in vivo initiates the homing process by introducing a
      double-strand cut in the approximately 35 bp recognition sequence. At 1.35 A
      resolution, the crystal structure of PI-SceI domain I provides a detailed view of
      the part of the protein that is responsible for tight and specific DNA binding. A
      geometry-based docking of the 75 degrees bent recognition sequence to the full
      length protein implies a conformational change or hinge movement of a subdomain
      of domain I, the tongs part, that is predicted to reach into the major groove
      near base pairs +16 to +18.

PMID- 12235382
TI  - Secondary structure polymorphism in Oxytricha nova telomeric DNA.
AB  - Tandem repeats of the telomeric DNA sequence d(T4G4) of Oxytricha nova are
      capable of forming unusually stable secondary structures incorporating Hoogsteen
      hydrogen bonding interactions. The biological significance of such DNA structures
      is supported by evidence of specific recognition of telomere end-binding proteins
      in the crystal state. To further characterize structural polymorphism of
      Oxytricha telomeric DNAs, we have obtained and interpreted Raman, ultraviolet
      resonance Raman (UVRR) and circular dichroism (CD) spectra of the tandem repeats
      d(G4T4G4) (Oxy1.5), d(T4G4)2 (Oxy2) and dT6(T4G4)2 (T6Oxy2) and related non
      telomeric isomers in aqueous salt solutions. Raman markers of Oxy1.5 identify
      both C2'-endo/anti and C2'-endo/syn conformations of the deoxyguanosine residues
      and Hoogsteen hydrogen bonded guanine quartets, consistent with the quadruplex
      fold determined previously by solution NMR spectroscopy. Raman, UVRR and CD
      signatures and Raman dynamic measurements, to monitor imino NH-->ND exchanges,
      show that the Oxy1.5 antiparallel quadruplex fold is distinct from the hairpin
      structures of Oxy2 and T6Oxy2, single-stranded structures of d(TG)8 and dT6(TG)8
      and previously reported quadruplex structures of d(T4G4)4 (Oxy4) and dG12.
      Spectral markers of the telomeric and telomere-related DNA structures are
      tabulated and novel Raman and UVRR indicators of thymidine and deoxyguanosine
      conformations are identified. The results will be useful for probing structures
      of Oxytricha telomeric repeats in complexes with telomere end-binding proteins.

PMID- 12235381
TI  - Secondary structure and DNA binding by the C-terminal domain of the
      transcriptional activator NifA from Klebsiella pneumoniae.
AB  - The NifA protein of Klebsiella pneumoniae is required for transcriptional
      activation of all nitrogen fixation (nif) operons except the regulatory nifLA
      genes. At these operons, NifA binds to an upstream activator sequence (UAS), with
      the consensus TGT-N(10)-ACA, via a C-terminal DNA-binding domain (CTD). Binding
      of the activator to this upstream enhancer-like sequence allows NifA to interact
      with RNA polymerase containing the alternative sigma factor, sigma(54). The
      isolated NifA CTD is monomeric and binds specifically to DNA in vitro as shown by
      DNase I footprinting. Heteronuclear 3D NMR experiments have been used to assign
      the signals from the protein backbone. Three alpha-helices have been identified,
      based on secondary chemical shifts and medium range Halpha(i)-NH(i)( + 1), and
      NH(i)-NH(i)( + 1) NOEs. On addition of DNA containing a half-site UAS, several
      changes are observed in the NMR spectra, allowing the identification of residues
      that are most likely to interact with DNA. These occur in the final two helices
      of the protein, directly confirming that DNA binding is mediated by a helix-turn
      helix motif.

PMID- 12235383
TI  - Density of points clustering, application to transcriptomic data analysis.
AB  - With the increasing amount of data produced by high-throughput technologies in
      many fields of science, clustering has become an integral step in exploratory
      data analysis in order to group similar elements into classes. However, many
      clustering algorithms can only work properly if aided by human expertise. For
      example, one parameter which is crucial and often manually set is the number of
      clusters present in the analyzed set. We present a novel stopping rule to find
      the optimal number of clusters based on the comparison of the density of points
      inside the clusters and between them. The method is evaluated on synthetic as
      well as on real transcriptomic data and compared with two current methods.
      Finally, we illustrate its usefulness in the analysis of the expression profiles
      of promyelocytic cells before and after treatment with all-trans retinoic acid.
      Simultaneous clustering for gene regulation and absolute initial expression
      levels allowed the identification of numerous genes associated with signal
      transduction revealing the complexity of retinoic acid signaling.

PMID- 12235384
TI  - Endogenous expression of a high-affinity pseudoknot RNA aptamer suppresses
      replication of HIV-1.
AB  - Aptamers, small oligonucleotides derived from an in vitro evolution process
      called SELEX, are promising therapeutic and diagnostic agents. Although very
      effective in vitro, only a few examples are available showing their potential in
      vivo. We have analyzed the effect of a well characterized pseudoknot RNA aptamer
      selected for tight binding to human immunodeficiency virus (HIV) type 1 reverse
      transcriptase on HIV replication. Transient intracellular expression of a
      chimeric RNA consisting of the human initiator tRNA(Met) (tRNA(Meti))/aptamer
      sequence in human 293T cells showed inhibition of HIV particle release by >75%
      when the cells were co-transfected with proviral HIV-1 DNA. Subsequent virus
      production of human T-lymphoid C8166 cells, infected with viral particles derived
      from co-transfected 293T cells, was again reduced by >75% as compared with the
      control. As the observed effects are additive, in this model for virus spread,
      the total reduction of HIV particle formation by transient intracellular
      expression of the pseudoknot RNA aptamer amounts to >95%. Low-dose HIV infection
      of human T cells stably expressing the aptamer did not show any virus replication
      over a period of 35 days. This is the first example of an RNA aptamer selected
      against a viral enzyme target to show powerful antiviral activity in HIV-1
      permissive human T-lymphoid cell lines.

PMID- 12235385
TI  - Sequence analysis of bacteriophage T4 DNA packaging/terminase genes 16 and 17
      reveals a common ATPase center in the large subunit of viral terminases.
AB  - Phage DNA packaging is believed to be driven by a rotary device coupled to an
      ATPase 'motor'. Recent evidence suggests that the phage DNA packaging motor is
      one of the strongest force-generating molecular motors reported to date. However,
      the ATPase center that is responsible for generating this force is unknown. In
      order to identify the DNA translocating ATPase, the sequences of the
      packaging/terminase genes of coliphages T4 and RB49 and vibriophages KVP40 and
      KVP20 have been analyzed. Alignment of the terminase polypeptide sequences
      revealed a number of functional signatures in the terminase genes 16 and 17. Most
      importantly, the data provide compelling evidence for an ATPase catalytic center
      in the N-terminal half of the large terminase subunit gp17. An analogous ATPase
      domain consisting of conserved functional signatures is also identified in the
      large terminase subunit of other bacteriophages and herpesviruses. Interestingly,
      the putative terminase ATPase domain exhibits some of the common features found
      in the ATPase domain of DEAD box helicases. Residues that would be critical for
      ATPase catalysis and its coupling to DNA packaging are identified. Com binatorial
      mutagenesis shows that the predicted threonine residues in the putative ATPase
      coupling motif are indeed critical for function.

PMID- 12235386
TI  - Topoisomerase III is required for accurate DNA replication and chromosome
      segregation in Schizosaccharomyces pombe.
AB  - The deletion of the top3(+) gene leads to defective nuclear division and
      lethality in Schizosaccharo myces pombe. This lethality is suppressed by
      concomitant loss of rqh1(+), the RecQ helicase. Despite extensive investigation,
      topoisomerase III function and its relationship with RecQ helicase remain poorly
      understood. We generated top3 temperature-sensitive (top3-ts) mutants and found
      these to be defective in nuclear division and cytokinesis and to be sensitive to
      DNA-damaging agents. A temperature shift of top3-ts cells to 37 degrees C, or
      treatment with hydroxyurea at the permissive temperature, caused an increase in
      'cut' (cell untimely torn) cells and elevated rates of minichromosome loss. The
      viability of top3-ts cells was decreased by a temperature shift during S-phase
      when compared with a similar treatment in other cell cycle stages. Furthermore,
      the top3-ts mutant was not sensitive to M-phase specific drugs. These results
      indicate that topoisomerase III may play an important role in DNA metabolism
      during DNA replication to ensure proper chromosome segregation. Our data are
      consistent with Top3 acting downstream of Rqh1 to process the toxic DNA structure
      produced by Rqh1.

PMID- 12235387
TI  - Oligomerization of the telomerase reverse transcriptase from Euplotes crassus.
AB  - The telomerase ribonucleoprotein reverse transcriptase uses its RNA subunit as a
      template to synthesize telomeric repeats and maintain telomere tracts on
      chromosome ends. In the ciliate Euplotes crassus, the core telomerase
      ribonucleoprotein particle undergoes a developmentally programmed assembly into
      three higher order complexes after mating. Here, we provide evidence using
      oligonucleotide-directed affinity purification that all of the E.crassus
      telomerase complexes contain at least two enzyme active sites. Furthermore, we
      show using co-immunoprecipitation experiments that EcTERT, the telomerase
      catalytic subunit, undergoes multimerization in vitro. Two independent
      interaction domains were identified in EcTERT, one at the N-terminus that spans
      amino acids 186-354 and one at the C-terminus that spans amino acids 755-857.
      Unexpectedly, we found that TERT can form head-to-head, tail-to-tail and head-to
      tail oligomers in vitro, implying that E.crassus telomerase has the potential to
      assume different conformations in vivo. Together, these data indicate that
      oligomerization is a conserved feature of telomerase and that the minimal
      functional unit of the enzyme is a dimer.

PMID- 12235389
TI  - Site-directed mutagenesis reveals roles for conserved amino acid residues in the
      hexameric DNA helicase DnaB from Bacillus stearothermophilus.
AB  - Site-directed mutagenesis studies on conserved amino acid residues within motifs
      H1, H1a, H2 and H3 of the hexameric replicative helicase DnaB from Bacillus
      stearothermophilus revealed specific functions associated with these residues. In
      particular, residues that coordinate a bound Mg2+ in the active site (T217 and
      D320) are important for the function of the enzyme but are not required for the
      formation of stable hexamers. A conserved glutamic acid (E241) in motif H1a is
      likely to be involved in the activation of a water molecule for in line attack on
      the gamma-phosphate of the bound nucleotide during catalysis. A conserved
      glutamine (Q362) in motif H3 acts as a gamma-phosphate sensor and mediates the
      conformational coupling of nucleotide- and DNA-binding sites. The nature of the
      residue at this position is also important for the primase-mediated activation of
      DnaB, suggesting that primase uses the same conformational coupling pathway to
      induce its stimulatory effect on the activity of DnaB. Together, these mutations
      reveal a conservation of many aspects of biochemical activity in the active sites
      of monomeric and hexameric helicases.

PMID- 12235388
TI  - Identification of mRNA decapping activities and an ARE-regulated 3' to 5'
      exonuclease activity in trypanosome extracts.
AB  - mRNA turnover is a regulated process that contributes to the steady state level
      of cytoplasmic mRNA. The amount of each mRNA determines, to a large extent, the
      amount of protein produced by that particular transcript. In trypanosomes, there
      is little transcriptional regulation; therefore, differential mRNA stability
      significantly contributes to mRNA levels in each stage of the parasite life
      cycle. To investigate the enzymatic activities that contribute to mRNA turnover,
      we developed a cell-free system for mRNA turnover using the trypanosome
      Leptomonas seymouri. We identified a decapping activity that removed m(7)GDP from
      mRNAs that contain an m(7)GpppN cap at their 5' end. In yeast, the release of
      m(7)GDP by the pyrophosphatase Dcp1p/Dcp2p is a rate-limiting step in mRNA
      turnover. A secondary enzymatic activity, similar to the human cap scavenger
      activity, was identified in the trypanosome extracts. Both the human and
      trypanosome scavenger activities generate m(7)GMP from short capped RNA and are
      inhibited by addition in trans of m(7)GpppG. A third enzymatic activity uncovered
      in the parasite extracts functioned as a 3' to 5' exonuclease. Importantly, this
      exonuclease activity was stimulated by an AU-rich element present in the RNA. In
      summary, the cell-free system has defined several RNA turnover steps that likely
      contribute to regulated mRNA decay in trypanosomes.

PMID- 12235390
TI  - Mediation of the A/B-DNA helix transition by G-tracts in the crystal structure of
      duplex CATGGGCCCATG.
AB  - The crystal structure of the DNA dodecamer duplex CATGGGCCCATG lies on a
      structural continuum along the transition between A- and B-DNA. The dodecamer
      possesses the normal vector plot and inclination values typical of B-DNA, but has
      the crystal packing, helical twist, groove width, sugar pucker, slide and x
      displacement values typical of A-DNA. The structure shows highly ordered water
      structures, such as a double spine of water molecules against each side of the
      major groove, stabilizing the GC base pairs in an A-like conformation. The
      different hydration of GC and AT base pairs provides a physical basis for solvent
      dependent facilitation of the A<-->B helix transition by GC base pairs. Crystal
      structures of CATGGGCCCATG and other A/B-DNA intermediates support a 'slide
      first, roll later' mechanism for the B-->A helix transition. In the distribution
      of helical parameters in protein-DNA crystal structures, GpG base steps show A
      like properties, reflecting their innate predisposition for the A conformation.

PMID- 12235391
TI  - Synthesis of stable-isotope enriched 5-methylpyrimidines and their use as probes
      of base reactivity in DNA.
AB  - A specific and efficient method is presented for the conversion of 2'
      deoxyuridine to thymidine via formation and reduction of the intermediate 5
      hydroxymethyl derivative. The method has been used to generate both thymidine and
      5-methyl-2'-deoxycytidine containing the stable isotopes 2H, 13C and 15N.
      Oligodeoxyribonucleotides have been constructed with these mass-tagged bases to
      investigate sequence-selectivity in hydroxyl radical reactions of pyrimidine
      methyl groups monitored by mass spectrometry. Studying the reactivity of 5
      methylcytosine (5mC) is difficult as the reaction products can deaminate to the
      corresponding thymine derivatives, making the origin of the reaction products
      ambiguous. The method reported here can distinguish products derived from 5mC and
      thymine as well as investigate differences in reactivity for either base in
      different sequence contexts. The efficiency of formation of 5-hydroxymethyluracil
      from thymine is observed to be similar in magnitude in two different sequence
      contexts and when present in a mispair with guanine. The oxidation of 5mC
      proceeds slightly more efficiently than that of thymine and generates both 5
      hydroxymethylcytosine and 5-formylcytosine but not the deaminated products.
      Thymine glycol is generated by both thymine and 5mC, although with reduced
      efficiency for 5mC. The method presented here should be widely applicable,
      enabling the examination of the reactivity of selected bases in DNA.

PMID- 12235393
TI  - Melting studies of dangling-ended DNA hairpins: effects of end length, loop
      sequence and biotinylation of loop bases.
AB  - The effects of 3' single-strand dangling-ends of different lengths, sequence
      identity of hairpin loop, and hairpin loop biotinylation at different loop
      residues on DNA hairpin thermodynamic stability were investigated. Hairpins
      contained 16 bp stem regions and five base loops formed from the sequence, 5'
      TAGTCGACGTGGTCC-N5-GGACCACGTCGACTAG-E(n)-3'. The length of the 3' dangling-ends
      (E(n)) was n = 13 or 22 bases. The identities of loop bases at positions 2 and 4
      were varied. Biotinylation was varied at loop base positions 2, 3 or 4. Melting
      buffers contained 25 or 115 mM Na+. Average t(m) values for all molecules were
      73.5 and 84.0 degrees C in 25 and 115 mM Na+, respectively. Average two-state
      parameters evaluated from van't Hoff analysis of the melting curve shapes in 25
      mM Na+ were DeltaH(vH) = 84.8 +/- 15.5 kcal/mol, DeltaS(vH) = 244.8 +/- 45.0
      cal/K.mol and DeltaG(vH) = 11.9 +/- 2.1 kcal/mol. In 115 mM Na+, two-state
      parameters were not very different at DeltaH(vH) = 80.42 +/- 12.74 kcal/mol,
      DeltaS(vH) = 225.24 +/- 35.88 cal/K.mol and DeltaG(vH) = 13.3 +/- 2.0 kcal/mol.
      Differential scanning calorimetry (DSC) was performed to test the validity of the
      two-state assumption and evaluated van't Hoff parameters. Thermodynamic
      parameters from DSC measurements (within experimental error) agreed with van't
      Hoff parameters, consistent with a two-state process. Overall, dangling-end DNA
      hairpin stabilities are not affected by dangling-end length, loop biotinylation
      or sequence and vary uniformly with [Na+]. Consider able freedom is afforded when
      designing DNA hairpins as probes in nucleic acid based detection assays, such as
      microarrays.

PMID- 12235392
TI  - DNA-PK-dependent binding of DNA ends to plasmids containing nuclear matrix
      attachment region DNA sequences: evidence for assembly of a repair complex.
AB  - We find that nuclear protein extracts from mammalian cells contain an activity
      that allows DNA ends to associate with circular pUC18 plasmid DNA. This activity
      requires the catalytic subunit of DNA-PK (DNA-PKcs) and Ku since it was not
      observed in mutants lacking Ku or DNA-PKcs but was observed when purified Ku/DNA
      PKcs was added to these mutant extracts. Purified Ku/DNA-PKcs alone did not
      produce association of DNA ends with plasmid DNA suggesting that additional
      factors in the nuclear extract are necessary for this activity. Competition
      experiments between pUC18 and pUC18 plasmids containing various nuclear matrix
      attachment region (MAR) sequences suggest that DNA ends preferentially associate
      with plasmids containing MAR DNA sequences. At a 1:5 mass ratio of MAR to pUC18,
      approximately equal amounts of DNA end binding to the two plasmids were observed,
      while at a 1:1 ratio no pUC18 end binding was observed. Calculation of relative
      binding activities indicates that DNA end-binding activities to MAR sequences was
      7-21-fold higher than pUC18. Western analysis of proteins bound to pUC18 and MAR
      plasmids indicates that XRCC4, DNA ligase IV and scaffold attachment factor A
      preferentially associate with the MAR plasmid in the absence or presence of DNA
      ends. In contrast, Ku and DNA-PKcs were found on the MAR plasmid only in the
      presence of DNA ends suggesting that binding of these proteins to DNA ends is
      necessary for their association with MAR DNA. The ability of DNA-PKcs/Ku to
      direct DNA ends to MAR and pUC18 plasmid DNA is a new activity for DNA-PK and may
      be important for its function in double-strand break repair. A model for DNA
      repair based on these observations is presented.

PMID- 12235394
TI  - Binding affinity of Escherichia coli RNA polymerase*sigma54 holoenzyme for the
      glnAp2, nifH and nifL promoters.
AB  - Escherichia coli RNA polymerase associated with the sigma54 factor (RNAP*sigma54)
      is a holoenzyme form that transcribes a special class of promoters not recognized
      by the standard RNA polymerase*sigma70 com plex. Promoters for RNAP*sigma54 vary
      in their overall 'strength' and show differences in their response to the
      presence of DNA curvature between enhancer and promoter. In order to examine
      whether these effects are related to the promoter affinity, we have determined
      the equilibrium dissociation constant K(d) for the binding of RNAP*sigma54 to the
      three promoters glnAp2, nifH and nifL. Binding studies were conducted by
      monitoring the changes in fluorescence anisotropy upon titrating RNAP*sigma54 to
      carboxyrhodamine-labeled DNA duplexes. For the glnAp2 and nifH promoters similar
      values of K(d) = 0.94 +/- 0.55 nM and K(d) = 0.85 +/- 0.30 nM were determined at
      physiological ionic strength, while the nifL promoter displayed a significantly
      weaker affinity with K(d) = 8.5 +/- 1.9 nM. The logarithmic dependence of K(d) on
      the ionic strength I was -Deltalog(K(d))/Deltalog(I) = 6.1 +/- 0.5 for the
      glnAp2, 5.2 +/- 1.2 for the nifH and 2.1 +/- 0.1 for the nifL promoter. This
      suggests that the polymerase can form fewer ion pairs with the nifL promoter,
      which would account for its weaker binding affinity.

PMID- 12235395
TI  - High throughput parallel synthesis of oligonucleotides with 1536 channel
      synthesizer.
AB  - A 1536 channel oligonucleotide synthesizer, the MultiSyn, was developed with the
      capability to simultaneously synthesize 1536 oligonucleotides of 20mer length in
      10 h. The instrument was designed to synthesize different sequences of various
      lengths in micro-wells and has synthesized oligonucleotides as long as 119 nt
      with reasonably good yields using CPG beads of 1000 A pore size. The instrument
      consists of four 384 channel synthesis modules. Phosphoramidite chemistry was
      employed and step yields as high as 99.3% were achieved. The enhancement of
      oligonucleotide synthesis throughput is accomplished by increasing the spatial
      density of reaction wells. We have identified several parameters that are
      critical in achieving a good synthesis yield and negligible failure rate in small
      reaction wells. The coefficient of variation (CV) of product yields in 1536
      reaction wells was 20%. The quality of the product was examined by capillary
      electrophoresis and mass spectrometry. The instrument has robustly synthesized
      oligonucleotides of various lengths for use as primers and probes for PCR
      amplifications, oligonucleotide microarrays and genotyping applications. This
      high throughput oligonucleotide synthesizer is a useful instrument for genomic
      applications, which require tens of thousands of probes or primers in a short
      time.

PMID- 12235396
TI  - Tripartite molecular beacons.
AB  - Molecular beacons (MBs) are hairpin-like fluorescent DNA probes that have single
      mismatch detection capability. Although they are extremely useful for many
      solution-based nucleic acid detections, MBs are expensive probes for applications
      that require the use of a large number of different DNA probes due to the high
      cost and tedious procedures associated with probe synthesis and purification. In
      addition, since both ends of MB probes are covalently modified with chromophores,
      they do not offer the flexibility for fluorophore change and the capability for
      surface immobilization through free DNA ends. In this report, we describe an
      alternative form of MB, denoted tripartite molecular beacon (TMB), that may help
      overcome these problems. A TMB uses an unmodified oligodeoxyribonucleotide that
      forms a MB-like structure with two universal single-stranded arms to bring on a
      universal pair of oligodeoxyribonucleotides modified separately with a
      fluorophore and a quencher. We found that TMBs are as effective as standard MBs
      in signaling the presence of matching nucleic acid targets and in precisely
      discriminating targets that differ by a single nucleotide. TMBs have the
      necessary flexibility that may make MBs more affordable for various nucleic acid
      detection applications.

PMID- 12235397
TI  - Rapid gene cloning using terminator primers and modular vectors.
AB  - We seek to create useful biological diversity by exploiting the modular nature of
      genetic information. In this report we describe experiments that focus on the
      modular nature of plasmid cloning vectors. Bacterial plasmids are modular
      entities composed of origins of replication, selectable markers and other
      components. We describe a new ligation-independent cloning method that allows for
      rapid and seamless assembly of vectors from component modules. We further
      demonstrate that gene cloning can be accomplished simultaneously with assembly of
      a modular vector. This approach provides considerable flexibility as it allows
      for 'menu driven' cloning of genes into custom assembled modular vectors.

PMID- 12235416
TI  - Evaluating the impact of organizational learning initiatives.
AB  - This article describes the process used to develop an evaluation model for
      organizational learning in a healthcare environment. This model moves away from
      the traditional focus on learner satisfaction and places greater emphasis on
      performance and impact evaluation. The evaluation model is grounded in the work
      of Kirkpatrick (1998) and Phillips (1991) and can be applied to a variety of
      programs. Using a highly practical approach, the model enables educators to
      determine the most appropriate level of evaluation for a learning opportunity and
      to identify effective and efficient strategies. This model could be readily
      adopted by healthcare organizations interested in enhancing the evaluation of the
      learning initiatives.

PMID- 12235417
TI  - A collaborative model: twenty healthcare agencies and academic institutions share
      resources to educate preceptors.
AB  - The Boston Collaborative Learning Group (BCLG), a 20-member consortium of
      healthcare agencies and academic institutions, originated in 1996 in response to
      a demand for innovative cost-effective measures. Directors of Staff Development
      and academicians collaborate and share resources in planning preceptor education
      programs. Over 750 Boston area nurses have attended 1 of 10 programs offered.
      This article provides an historical perspective on forming a consortium and the
      benefits of this collaborative model.

PMID- 12235418
TI  - The future roles of nurses.
AB  - Healthcare delivery in the United States is changing because of managed care and
      capitation. The future of hospital nursing is being reshaped because of the
      economic pressures of managed care and market-led health reforms. A variety of
      new healthcare job opportunities for nurses will now present themselves. Nurse
      leader roles will evolve to complement the new managed healthcare structure.
      Because of the organizational redesign of managed care, nurses will need to
      develop additional skills and education for these roles. This article discusses
      potential new roles nurses will occupy in a managed care environment.

PMID- 12235419
TI  - Preceptors' perceptions of a competency-based orientation.
AB  - The purpose of this study was to describe preceptors' perceptions of a competency
      based orientation. Results of a 26-item questionnaire that was distributed to all
      preceptors indicated the majority of preceptors agreed that 1. the identified
      core competencies were role- and unit-specific, and 2. competency-based
      orientation is an effective method of orientation. However, the majority of
      preceptors indicated that the length of time for completion of core competencies
      was insufficient; this may reflect in the new employee's ability to function as a
      competent practitioner. Learner-focused orientation programs that provide
      sufficient time for validation of competencies must be developed.

PMID- 12235420
TI  - Graduate students learn effective management.
AB  - This article describes an active learning approach used in a management seminar
      for master's students to assist them in internalizing knowledge gained in the
      seminar. Participating in a research project aimed at identifying the qualities
      of an effective nursing manager enabled students to improve their research
      abilities, examine their work environment, and thereby increase their motivation
      and satisfaction. The study results supported findings of earlier studies,
      emphasizing "human skills" as most important for effective management.

PMID- 12235421
TI  - W-H-E-E-L of Disaster.
AB  - Many states require long-term care facilities to develop mandatory training
      sessions on several safety, infection, and biohazard-related topics. The
      challenge for most facilities is how to make learning exciting and new. Many
      training sessions are mandatory, so the challenge for educators is how to take
      the boredom out of going to inservice programs. This article outlines an
      inservice program developed at Attic Angel Place in Madison, WI. Using the
      popular television show Wheel of Fortune as a model, the facility developed a
      similar game-like training program dealing with accident prevention, fire and
      tornado safety, and biohazardous materials. Of the facility's 175 full- and part
      time employees, 75 attended the "Wheel of Disaster."

PMID- 12235422
TI  - Creating and using staff development standards.
AB  - This article is an overview of the development of the revised Scope and Standards
      of Practice for Nursing Professional Development, published by the American
      Nurses Association in 2000. It provides some background information about the
      standards, and discusses implications for staff development educators. The
      framework for these revised standards is continuing competence, which is
      essential to promote evidence-based practice.

PMID- 12235423
TI  - Instant teaching tools.

PMID- 12235427
TI  - Why is it so important to ensure that women's health, gender-based competencies
      are woven into the fabric of undergraduate medical education?

PMID- 12235428
TI  - APGO Interdisciplinary women's health education retreat 2000. Executive summary.

PMID- 12235429
TI  - Interdisciplinary women's health education: the perspective of two students.

PMID- 12235430
TI  - Corporate support: the cornerstone of the retreat's success.

PMID- 12235431
TI  - A longitudinal women's health curriculum: a multi-method, multiperspective needs
      assessment.
AB  - OBJECTIVES: To define critical competencies in women's health for medical student
      education and to assess the degree to which they are taught. STUDY DESIGN: A set
      of competencies in women's health was developed. A multi-method needs assessment
      was implemented. RESULTS: Faculty and student evaluations revealed no major areas
      of disagreement but did identify major deficits in the basic sciences including
      the physiologic influence of estrogen on nongynecologic organ systems and of
      androgen on various organ systems, nutrition, and alternative medicine and the
      difference between the sexes in disease processes, presentation, and treatment.
      In the clinical years, there are important deficits in the teaching of diseases
      unique to women, limited attention to psychosocial aspects of women's health, and
      no cohesive teaching of a gender-specific approach to clinical evaluation.
      CONCLUSION: In the medical school curriculum, gender's effect on disease is
      inadequately addressed. An integrated longitudinal approach to gender-specific
      medicine is needed.

PMID- 12235432
TI  - Women's health competencies in the undergraduate psychiatry curriculum: past and
      future.
AB  - OBJECTIVE: To review the current psychiatry model clerkship objectives for their
      inclusion of women's health competencies and advise changes in light of
      recommendations of psychiatric educators and those developed at the Association
      of Professors of Gynecology and Obstetrics (APGO) Women's Health Education
      Retreat 2000. STUDY DESIGN: The clerkship objectives promulgated by the
      Association of Directors of Medical Student Education in Psychiatry (ADMSEP) were
      reviewed for their relevance to women's health. ADMSEP members were surveyed at
      their 1997 annual meeting and again by means of their listserve in 2000 for
      opinions regarding inclusion of women's health topics in their curricula.
      RESULTS: The current objectives imply many women's health competencies. Those
      pertaining to abuse are particularly comprehensive. Survey data suggest that
      educators perceive that psychiatric aspects of reproductive functioning,
      violence, and trauma; gender differences in prevalence, presentation, and
      treatment of psychiatric disorders; and gender aspects of the doctor-patient
      relationship merit particular emphasis in the clerkship curriculum. CONCLUSIONS:
      Women's health competencies are broadly but implicitly represented in the
      psychiatry clerkship objectives as currently formulated. Revisions should
      encompass more explicit appreciation of gender differences and specific
      additional knowledge, skills, and attitudes.

PMID- 12235433
TI  - Personal digital assistant for "real time" assessment of women's health in the
      clinical years.
AB  - OBJECTIVE: To assess in "real time" the degree to which women's health
      competencies are addressed in the clinical curriculum by using a personal digital
      assistant. STUDY DESIGN: Competencies for women's health were developed. Twelve
      students were supplied with a personal digital assistant, pre-loaded with a
      patient log system, for use in assessment of the inclusion of these competencies
      in the clinical arena. The students received instruction on completing the log
      for each patient for whom they were primarily responsible. RESULTS: There were
      2690 total encounters. In clerkships other than obstetrics and gynecology, gender
      was discussed in 10% to 20% of encounters. Other than obstetrics and gynecology
      diagnostic categories, no more than 15% of diagnoses included gender discussion.
      CONCLUSION: Student recording of patient encounters reveals a minimal amount of
      women's health discussion in the clinical years; however, the personal digital
      assistant is an effective tool with which to monitor curriculum content in the
      clinical setting.

PMID- 12235434
TI  - Evaluating women's health and gender.
AB  - Current medical education objectives rarely address the context of women's health
      and gender. Some educators may serendipitously focus on, for example, the effect
      of powerlessness or sex role stereotypes on health; however, more systematic
      teaching is needed. The adoption and evaluation of explicit learning objectives
      addressing behaviors and context by licensing bodies and medical schools will
      increase graduates' understanding of the determinants of women's health. We
      identify important educational objectives and evaluation techniques and
      strategies for their integration.

PMID- 12235435
TI  - The process of translating women's health care competencies into educational
      objectives.
AB  - "Women's Health Care Competencies for Medical Students" lists the competencies
      undifferentiated medical students should be able to demonstrate before
      graduation. The Association of Professors of Gynecology and Obstetrics (APGO) was
      among the groups asked to convert specified competencies into educational
      objectives. Working individually, APGO's Undergraduate Medical Education
      Committee members used APGO's Medical Student Educational Objectives, Seventh
      Edition, to construct objectives appropriate to preassigned competencies.
      Referring to the work of Miller, members determined the level of professional
      competence medical students should reach for each objective. Members also
      selected evaluation tools appropriate for the skill and its competency level from
      the Toolbox of Assessment Methods created by the Accreditation Council for
      Graduate Medical Education and the American Board of Medical Specialties. The
      group collectively revised the work of its members using a standard format to
      generate the final product.

PMID- 12235436
TI  - Women's health in the medical school curriculum: Building support for the
      adoption of core competencies.
AB  - Local adoption of the Association of Professors in Gynecology and Obstetrics
      women's health care competencies for medical students must be preceded by
      significant institutional groundwork. Nationally developed guidelines play an
      important role in persuading teaching faculty of the importance of including
      women's health and in augmenting institution-specific efforts.

PMID- 12235437
TI  - A student-initiated interactive course as a model for teaching reproductive
      health.
AB  - OBJECTIVE: Medical students at Stanford University established an elective
      lecture series in reproductive health to teach 10 women's health competencies to
      preclinical medical students. In the second year, student organizers implemented
      interactive components to improve the number of competencies students learned.
      STUDY DESIGN: We surveyed students from the first two years this series was
      offered to assess their preferred modes of learning and the number of
      competencies students perceived they had gained. Students were asked to self
      assess their learning of key reproductive health competencies taught in the
      course. RESULTS: We identified 4 factors associated with statistically
      significant improvements in the number of competencies students learned,
      according to self-assessment. CONCLUSION: Students who felt they learned more
      competencies agreed that they were active participants in the course, that their
      preferred style of learning was matched by the course, and that they had received
      academic credit for the course. Furthermore, students who attended an innovative
      reproductive health fair organized by students participating in the course
      perceived that they had learned significantly more competencies. We expect these
      self-assessed improvements to correlate with increased demonstration of the
      competencies as students progress to the clinical level.

PMID- 12235438
TI  - From the wall to the web: the use of bulletin boards and a web site to
      disseminate information about sex, gender and women's health.
AB  - Strategically placed bulletin boards were used to disseminate information about
      sex and gender biology and women's health competencies to medical students and
      faculty. This has proved to be an effective tool to rapidly introduce material
      when the curriculum cannot accommodate this new material. With the popularity of
      the internet, these bulletin boards were transferred to our website and became
      accessible to a greater audience both within and outside the medical center. This
      article describes the bulletin board sites, their content, and some of the
      benefits and problems visitors had.

PMID- 12235439
TI  - How virtual reality may enhance training in obstetrics and gynecology.
AB  - OBJECTIVE: Contemporary training in obstetrics and gynecology is aimed at the
      acquisition of a complex set of skills oriented to both the technical and
      personal aspects of patient care. The ability to create clinical simulations
      through virtual reality (VR) may facilitate the accomplishment of these goals.
      The purpose of this paper is 2-fold: (1) to review the circumstances and
      equipment in industry, science, and education in which VR has been successfully
      applied, and (2) to explore the possible role of VR for training in obstetrics
      and gynecology and to suggest innovative and unique approaches to enhancing this
      training. MATERIAL AND METHODS: Qualitative assessment of the literature
      describing successful applications of VR in industry, law enforcement, military,
      and medicine from 1995 to 2000. Articles were identified through a computer-based
      search using Medline, Current Contents, and cross referencing bibliographies of
      articles identified through the search. RESULTS: One hundred and fifty-four
      articles were reviewed. This review of contemporary literature suggests that VR
      has been successfully used to simulate person-to-person interactions for training
      in psychiatry and the social sciences in a variety of circumstances by using real
      time simulations of personal interactions, and to launch 3-dimensional trainers
      for surgical simulation. These successful applications and simulations suggest
      that this technology may be helpful and should be evaluated as an educational
      modality in obstetrics and gynecology in two areas: (1) counseling in
      circumstances ranging from routine preoperative informed consent to intervention
      in more acute circumstances such as domestic violence or rape, and (2) training
      in basic and advanced surgical skills for both medical students and residents.
      CONCLUSION: Virtual reality is an untested, but potentially useful, modality for
      training in obstetrics and gynecology. On the basis of successful applications in
      other nonmedical and medical areas, VR may have a role in teaching essential
      elements of counseling and surgical skill acquisition.

PMID- 12235440
TI  - Concept mapping: a tool to bridge the disciplinary divide.
AB  - The American College of Women's Health Physicians has been exploring an on-line
      educational tool-concept mapping-to facilitate the development of an
      interdisciplinary and woman-centered women's health curriculum, and to implement
      The Women's Health Care Competencies for Medical Students. By using an on-line
      concept map of the menstrual cycle, we have built upon a standard piece of
      curricula that describes a unique aspect of female physiology and transformed it
      into a knowledge framework that builds capacity. The concept map highlights
      relationships between concepts and across disciplines, connecting the
      competencies to enable meaningful learning so that a learner can adapt their
      knowledge to multiple settings, incorporate new learning, and generate new
      knowledge to grow the interdisciplinary field of women's health. The on-line
      format allows access from multiple sites and courses, and allows the curricula to
      grow organically over time without upsetting current curricular design.

PMID- 12235441
TI  - Introduction of contextual legal issues in an interdisciplinary program for the
      study of ethical dilemmas in obstetrics and gynecology for third-year medical
      students.
AB  - OBJECTIVE: To introduce contextual legal issues, and the role of law in resolving
      ethical dilemmas, in a women's health ethics curriculum for third-year medical
      students. METHODS: Seventeen third-year medical students at Emory University
      School of Medicine, rotating on an 8-week obstetrics and gynecology clerkship,
      and 8 third-year law students from the Georgia State University College of Law
      attended four 1-hour ethics sessions conducted by an obstetrician and
      gynecologist, a law professor and an ethics fellow. Each student group completed
      a short survey to evaluate the effectiveness of the sessions. RESULTS: The
      overwhelming majority, 20 of 25 (80%) of the combined student group ranked the
      sessions a level 6 or 7 (the highest level) and suggested continuation of the
      interdisciplinary group format. The majority of the combined student group, 14 of
      25 (56%), also viewed the multidisciplinary nature of the group as the most
      helpful aspect of the sessions. For the medical students, additional helpful
      aspects included having the legal perspective from persons who actually study the
      law. For the law students, other helpful aspects included the informal roundtable
      discussion format and the structured 4-quadrant model. CONCLUSION: Incorporation
      of medical and law students into a discussion group for resolving ethical
      dilemmas is a satisfying method for discussion of legal issues in the women's
      health ethics curriculum. It enriches the understanding of students from both
      disciplines.

PMID- 12235442
TI  - An interdisciplinary course in women's health integrating basic and clinical
      sciences: clinical anatomy and women's health.
AB  - Traditionally, undergraduate medical education is divided into preclinical and
      clinical years, with basic sciences taught during the first years and clinical
      sciences taught during the latter years. In an effort to better integrate the
      basic and clinical sciences in undergraduate medical education, and focus on
      women's health, we have developed a new interdisciplinary fourth-year elective at
      the University of Michigan Medical School. The elective, titled "Clinical Anatomy
      and Women's Health," is a joint effort between the Division of Anatomical
      Sciences and the Department of Obstetrics and Gynecology at the University of
      Michigan Health System. During the course students participate in didactic,
      laboratory, cadaveric dissection, and clinical-correlate sessions that focus on
      gynecologic anatomy and clinical issues in women's health. Educational goals and
      learning objectives were used to assess the effectiveness of the curriculum;
      revisions, based on outcomes of the educational assessment, will be implemented
      in the next offering of the course. Preliminary data from the first offering of
      the course in February 2002 are provided. The goals of this course include
      integrating basic science and clinical concepts while reducing the division
      between preclinical and clinical medical education, addressing issues of women's
      health, and encouraging lifelong learning by using basic science concepts and
      techniques of discovery in clinical practice.

PMID- 12235443
TI  - Equivalence approaches.

PMID- 12235444
TI  - Evaluation of potential losartan-phenytoin drug interactions in healthy
      volunteers.
AB  - BACKGROUND: Phenytoin, a cytochrome P450 (CYP) 2C9 substrate, has a narrow
      therapeutic index and nonlinear pharmacokinetics. Therefore there is the
      potential for significant concentration-related adverse effects when phenytoin is
      coadministered with other CYP2C9 substrates. Losartan, an antihypertensive agent,
      is also a substrate for CYP2C9. OBJECTIVE: Our objective was to assess the
      effects of losartan on the pharmacokinetics of phenytoin and the effects of
      phenytoin on the pharmacokinetics of losartan in a healthy population of
      volunteers. METHODS: A prospective, randomized, 3-period crossover study was
      conducted in 16 healthy volunteers with phenytoin alone, phenytoin in combination
      with losartan, and losartan alone. Each treatment was given for 10 days with a 3
      week washout period between treatments. On day 10, plasma concentrations of
      phenytoin and plasma and urine concentrations of losartan and its active
      carboxylic-acid metabolite E3174 were measured to determine steady-state
      pharmacokinetic parameters. RESULTS: Coadministration of losartan had no effect
      on the pharmacokinetics of phenytoin. Coadministration of phenytoin increased the
      mean area under the concentration-time curve from time zero to 24 hours [AUC(0
      24)] of losartan by 17% (355 +/- 220 ng x h/mL versus 427 +/- 177 ng x h/mL; P
      =.1), but this difference was not statistically significant. In the 14
      CYP2C9*1/*1 subjects, the mean AUC(0-24) of losartan was increased by 29% (284 +/
      84 ng x h/mL versus 402 +/- 128 ng x h/mL; P =.008). Coadministration of
      phenytoin significantly reduced the AUC(0-24) of E3174 by 63% (1254 +/- 256 ng x
      h/mL versus 466 +/- 174 ng x h/mL; P =.0001) and the formation clearance of
      losartan to E3174 (1.91 +/- 0.8 mL/h per kilogram versus 0.62 +/- 0.4 mL/h per
      kilogram; P =.0001). CONCLUSIONS: Losartan, a CYP2C9 substrate, had no effect on
      the pharmacokinetics of phenytoin. However, phenytoin inhibited the CYP2C9
      mediated conversion of losartan to E3174.

PMID- 12235445
TI  - Evaluation of peppermint oil and ascorbyl palmitate as inhibitors of cytochrome
      P4503A4 activity in vitro and in vivo.
AB  - OBJECTIVES: Our study was designed to determine the effect of peppermint oil and
      ascorbyl palmitate on cytochrome P4503A4 (CYP3A4) activity in vitro and oral
      bioavailability of felodipine in humans. METHODS: Reversible and mechanism-based
      inhibitions of nifedipine oxidation were studied in human liver microsomes. The
      oral pharmacokinetics of felodipine and its dehydrofelodipine metabolite were
      determined in 12 healthy volunteers after administration of felodipine, 10-mg
      extended-release tablet, with grapefruit juice (300 mL), peppermint oil (600 mg),
      ascorbyl palmitate (500 mg), or water in a randomized 4-way crossover study.
      RESULTS: Peppermint oil (inhibition constant [K(i)] = 35.9 +/- 3.3 microg/mL,
      mean +/- SEM) and 2 constituents, menthol (K(i) = 87.0 +/- 7.0 micromol/L), and
      menthyl acetate (K(i) = 124.0 +/- 7.0 micromol/L), produced reversible inhibition
      of nifedipine oxidation. Ascorbyl palmitate was more potent (K(i) = 12.3 +/- 0.5
      micromol/L). None of these substances were mechanism-based inhibitors. Grapefruit
      juice and peppermint oil increased the area under the curve (AUC) values of
      felodipine to 173% (range, 94%-280%; P <.01) and 140% (range, 77%-262%; P <.05),
      respectively, of those with water. They augmented the peak plasma concentration
      (C(max)) of felodipine and the AUC and C(max) of dehydrofelodipine but did not
      alter the half-life (t(1/2)) of either substance. Grapefruit juice decreased the
      dehydrofelodipine/felodipine AUC ratio, but peppermint oil did not. Ascorbyl
      palmitate did not change the pharmacokinetics of felodipine or dehydrofelodipine
      compared with water. CONCLUSIONS: Peppermint oil, menthol, menthyl acetate, and
      ascorbyl palmitate were moderately potent reversible inhibitors of in vitro
      CYP3A4 activity. Grapefruit juice increased the oral bioavailability of
      felodipine by inhibition of CYP3A4-mediated presystemic drug metabolism.
      Peppermint oil may also have acted by this mechanism. However, this requires
      further investigation. Ascorbyl palmitate did not inhibit CYP3A4 activity in
      vivo.

PMID- 12235446
TI  - Effect of levothyroxine administration on intestinal P-glycoprotein expression:
      consequences for drug disposition.
AB  - OBJECTIVE: Thyroid function alters the pharmacokinetics of many drugs; one
      example is the cardiac glycoside digoxin. Because digoxin disposition is affected
      by intestinal expression of P-glycoprotein, we hypothesized that thyroid hormones
      may regulate P-glycoprotein and influence disposition of P-glycoprotein
      substrates. METHODS: Duodenal expression of P-glycoprotein measured by reverse
      transcriptase-polymerase chain reaction of MDR1 messenger ribonucleic acid (mRNA)
      and by immunohistochemical examination was studied in 8 healthy volunteers (4 men
      and 4 women; age range, 22-29 years; body weight, 59-89 kg) before and after
      coadministration with levothyroxine (200 microg orally for 17 days), which
      resulted in suppression of thyroid-stimulating hormone. The pharmacokinetics of
      the P-glycoprotein substrate talinolol was assessed after intravenous (30 mg) and
      oral (100 mg) administration. RESULTS: Duodenal MDR1 mRNA expression and
      immunoreactive P-glycoprotein were increased 1.4-fold (not significant; P =.078)
      and 3.8-fold (P <.01), respectively, after administration of levothyroxine. The
      changes in P-glycoprotein expression were associated with minor alterations in
      talinolol half-life after both oral and intravenous administration. CONCLUSIONS:
      Expression of intestinal P-glycoprotein in humans appears to be influenced by
      thyroid hormones. The functional consequences need to be addressed in patients
      with hyperthyroidism.

PMID- 12235447
TI  - Clinical pharmacokinetics of irinotecan and its metabolites in relation with
      diarrhea.
AB  - OBJECTIVES: Our objective was to build population pharmacokinetic models that
      describe plasma concentrations of irinotecan (CPT-11) and its metabolites 7-ethyl
      10-hydroxycamptothecin (SN-38) and SN-38 glucuronide (SN-38G) and to investigate
      the pharmacokinetic-pharmacodynamic relationships between drug exposure and
      diarrhea, the major dose-limiting toxicity. METHODS: Data were obtained from 109
      patients (65 men and 44 women) who received 1.5-hour (range, 0.75- to 2.25-hour)
      intravenous infusions of irinotecan at doses that ranged from 100 to 350 mg/m(2);
      44 patients had a second course. The population pharmacokinetic models were
      developed to describe plasma concentration-time profiles. The area under the
      concentration-time curve from time zero to 60 hours [AUC (0-60)] was used as a
      measure of drug exposure to model the probabilities of diarrhea with use of a
      logistic regression model. RESULTS: A 3-compartment pharmacokinetic model best
      described the disposition of irinotecan, whereas SN-38 and SN-38G showed 2
      compartmental characteristics. The population estimate of clearance for
      irinotecan was 31.6 L/h, and the volume of distribution at steady-state (V(SS))
      was 263 L. The clearance divided by formation fraction (F(m)) was 712 L/h and
      66.8 L/h for SN-38 and SN-38G, respectively. The V(SS)/F(m) was 72,000 L for SN
      38 and 85.4 L for SN-38G. The frequencies of diarrhea scores in this study were
      46% (grade 0), 28% (grade 1), 20% (grade 2), 4% (grade 3), and 2% (grade 4).
      Significant correlations between AUC(0-60) and diarrhea scores were found for
      irinotecan (P <.05) and SN-38G (P <.01) but not for SN-38 or the biliary index.
      CONCLUSIONS: In this population analysis, irinotecan and SN-38G AUC values were
      appropriate predictors of the risk for diarrhea, and SN-38G AUC showed the
      stronger relationship of the two. The developed population models may be useful
      in further clinical development of this agent.

PMID- 12235448
TI  - Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in
      humans.
AB  - OBJECTIVES: Phytochemical-mediated modulation of cytochrome P450 (CYP) activity
      may underlie many herb-drug interactions. Single-time point phenotypic metabolic
      ratios were used to determine whether long-term supplementation of St John's
      wort, garlic oil, Panax ginseng, and Ginkgo biloba affected CYP1A2, CYP2D6,
      CYP2E1, or CYP3A4 activity. METHODS: Twelve healthy volunteers (6 females) were
      randomly assigned to receive either St John's wort, garlic oil, P ginseng, or G
      biloba for 28 days. For each subject, a 30-day washout period was interposed
      between each supplementation phase. Probe-drug cocktails of midazolam, caffeine,
      chlorzoxazone, and debrisoquin (INN, debrisoquine) were administered before
      supplementation (baseline) and at the end of supplementation. Presupplementation
      and postsupplementation phenotypic trait measurements were determined for CYP3A4,
      CYP1A2, CYP2E1, and CYP2D6 with the use of 1-hydroxymidazolam/midazolam serum
      ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6
      hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquin
      urinary recovery ratios (8-hour collection), respectively. RESULTS: Comparisons
      of presupplementation and postsupplementation ratios indicated that St John's
      wort significantly induced the activity of CYP2E1 and CYP3A4 (P <.0001). Among
      female subjects, St John's wort produced significantly greater increases in
      CYP3A4 phenotypic ratios that appeared to be unrelated to body mass index. This
      finding is suggestive of a sexual dimorphism in CYP3A4 inducibility. Garlic oil
      reduced CYP2E1 activity by 39% (P =.030), whereas no significant effect on CYP
      activity was observed for P ginseng and G biloba. CONCLUSIONS: Single-time point
      phenotypic metabolic ratios may provide a practical means of predicting CYP
      mediated herb-drug interactions in humans.

PMID- 12235449
TI  - Cytochrome P450 2E1 and 3A activities do not differ between Mexicans and European
      Americans.
AB  - OBJECTIVES: Population differences in the activity of various cytochrome P450
      (CYP) enzymes have been demonstrated on the basis of either genetic or
      environmental determinants. Hispanics are a large demographic group both
      worldwide and within the United States; hence the possibility of differences in
      metabolism between one such group-Mexicans-and a European-derived population was
      determined with respect to CYP2E1 and CYP3A. METHODS: Young healthy Mexican
      immigrants living in Los Angeles, Calif, who had maintained a traditional diet
      were compared with previously and identically studied groups of age-, sex-, and
      weight-matched European Americans who resided in middle Tennessee and ate a
      "western" diet (15 men and 15 women). In one study carried out in 15 women, the
      disposition of chlorzoxazone after an oral dose (250 mg) was compared. In the
      other investigation, all of the 15 subjects were men and received intravenous
      [(15)N(3)]-labeled midazolam (1 mg) and oral midazolam (2 mg) simultaneously to
      characterize the disposition of benzodiazepine in the two populations. RESULTS:
      Plasma concentration-time profiles of chlorzoxazone and its 6-hydroxy metabolite
      and the 0- to 24-hour urinary recovery of the latter were not different between
      Mexicans and European Americans. This indicates that CYP2E1 activity is similar
      in the two populations. Similarly, no significant intergroup differences were
      noted in the plasma concentration-time profiles of midazolam after either
      intravenous or oral administration. Accordingly, CYP3A does not appear to be
      different between Mexicans and European Americans. CONCLUSIONS: Similarity in the
      metabolism of chlorzoxazone between Mexicans and European Americans suggests that
      the risk associated with CYP2E1-mediated activation of procarcinogens is not
      different between these two populations. Likewise, the absence of any difference
      in the disposition of midazolam indicates that, from a pharmacokinetic
      standpoint, dosages of drugs metabolized by CYP3A need not be different between
      Mexicans and European Americans.

PMID- 12235450
TI  - Atovaquone plus chloroguanide versus mefloquine for malaria prophylaxis: a focus
      on neuropsychiatric adverse events.
AB  - OBJECTIVES: We performed a prospective, double-blind, randomized study to compare
      the occurrence of neuropsychiatric adverse events and concentration impairment
      during prophylactic use of either mefloquine or atovaquone plus chloroguanide
      (INN, proguanil). METHODS: Our potential study population consisted of all
      persons who were included in the MAL30010 trial at the Travel Clinic, Rotterdam,
      The Netherlands. All subjects were randomized to receive either active atovaquone
      (250 mg) plus chloroguanide (100 mg) daily plus a placebo for mefloquine weekly
      or active mefloquine (250 mg) weekly plus a placebo for atovaquone plus
      chloroguanide daily. Each subject was followed up from a baseline screening visit
      up to the index date, 7 days after he or she left the malaria-endemic area. We
      measured the interindividual and intraindividual changes in mood disturbance by
      means of the Dutch shortened Profile of Mood States and 3 domains of the
      Neurobehavioral Evaluation System, which included sustained attention, coding
      speed, and visuomotor accuracy between baseline and follow-up visit. RESULTS: The
      cohort consisted of 119 subjects with a mean age of 35 years. A significant
      deterioration in depression, anger, fatigue, vigor, and total mood disturbance
      domains occurred during use of mefloquine but not during use of atovaquone plus
      chloroguanide. Stratification for sex showed between-treatment differences in
      female patients but not in male patients. In both treatment groups, sustained
      attention deteriorated after travel, especially with increased duration of stay.
      CONCLUSIONS: Prophylactic use of mefloquine was associated with significantly
      higher scores on scales for depression, anger, and fatigue and lower scores for
      vigor than prophylactic use of atovaquone plus chloroguanide.

PMID- 12235451
TI  - Losartan and lercanidipine attenuate low-density lipoprotein oxidation in
      patients with hypertension and type 2 diabetes mellitus: a randomized,
      prospective crossover study.
AB  - OBJECTIVES: Lipoprotein oxidation, dyslipidemia, and hypertension are important
      underlying causes of accelerated atherosclerosis in patients with diabetes
      mellitus. The potential of antihypertensive medications to reduce lipid oxidation
      is, therefore, an important determinant in the choice of agents for patients with
      diabetes mellitus. The aim of this study was to compare the lowering effect of a
      new dihydropyridine calcium antagonist, lercanidipine, with that of the first
      angiotensin-receptor blocker, losartan, on low-density lipoprotein (LDL)
      oxidation. METHODS: Forty patients in metabolically stable condition who had type
      2 diabetes mellitus with hypertension were studied in this single-blind,
      randomized, prospective crossover study, comprising 2 treatment periods of 16
      weeks each, separated by a 4-week washout period. LDL oxidation was evaluated by
      dialdehyde analysis by means of the thiobarbituric acid-reactive substances assay
      with and without cupric sulfate, as well as determination of conjugated dienes in
      the LDL lipid extract. RESULTS: Lercanidipine and losartan both significantly
      reduced the propensity of the serum to oxidize LDL (P =.001). With one method of
      estimation (conjugated dienes), the effect of lercanidipine was superior to that
      of losartan (P =.04). Losartan lowered urinary albumin excretion but
      lercanidipine did not. CONCLUSIONS: Both lercanidipine and losartan attenuate LDL
      oxidation in patients with type 2 diabetes mellitus and hypertension. This
      observation may offer insight into the mechanisms of the therapeutic effects of
      these agents in patients with diabetes mellitus.

PMID- 12235452
TI  - The pharmacokinetics and pharmacodynamics of enoxaparin in obese volunteers.
AB  - OBJECTIVES: The objective of this study was to compare the pharmacokinetics of
      the low-molecular-weight heparin enoxaparin in obese and nonobese volunteers, by
      means of two administration regimens. METHODS: Enoxaparin was administered
      subcutaneously (1.5 mg/kg once daily for 4 days) and in a single 6-hour infusion
      (1.5 mg/kg) to 24 obese volunteers and 24 age-, sex-, and height-matched nonobese
      volunteers in a randomized, open-label, 2-way crossover design. Blood plasma was
      assessed for anti-Xa and anti-IIa activity and activated partial thromboplastin
      time. RESULTS: After subcutaneous administration, steady-state exposure was
      achieved after the second dose in nonobese volunteers and after the third dose in
      obese volunteers. Time to maximum anti-Xa activity was 1 hour longer in obese
      volunteers, but maximum anti-Xa activity was similar in both groups. For anti-Xa
      activity, exposure at steady-state was 16% higher in obese volunteers than in
      nonobese volunteers (90% confidence interval, 108%-125%). After intravenous
      infusion, total body clearance and volume of distribution at steady state were
      higher in obese volunteers than in nonobese volunteers, but when adjusted for
      weight, these values were about 10% lower in obese volunteers. Anti-IIa activity
      after subcutaneous administration did not differ significantly between obese and
      nonobese volunteers. Pharmacodynamic analysis of activated partial thromboplastin
      time showed similar results in obese and nonobese volunteers after both
      intravenous and subcutaneous administration. No deaths or serious adverse events
      occurred during the study. CONCLUSIONS: Enoxaparin was well tolerated when
      administered subcutaneously or intravenously, and there appears to be no need to
      modify the currently recommended dose for obese volunteers.

PMID- 12235453
TI  - Increased genotype frequency of N-acetyltransferase 2 slow acetylation in
      patients with rheumatoid arthritis.
AB  - OBJECTIVES: Acetylation polymorphism can alter therapeutic responses and toxicity
      to certain xenobiotics and may also be a factor that influences a patient's
      susceptibility to certain diseases. We investigated whether patients with
      rheumatoid arthritis (RA) differed from healthy individuals with regard to
      genotype of the polymorphic enzyme N-acetyltransferase 2 (NAT2). METHODS: NAT2
      polymorphism was compared in 118 healthy subjects and 82 patients with RA. NAT2
      alleles (*4, *5, *6, and *7) were determined by polymerase chain reaction
      restriction fragment length polymorphism methods with deoxyribonucleic acid
      extracted from peripheral blood. RESULTS: A statistically significant increase in
      the proportion of homozygous slow acetylators with 2 mutated alleles (84.1%) was
      found among patients with RA in comparison with healthy subjects (52.5%; P
      <.0001). The risk of development of RA was almost 5-fold greater in slow
      acetylators than in fast acetylators (odds ratio, 4.79; 95% confidence interval,
      2.28-10.21). There was no correlation between NAT2 polymorphism and presence of
      rheumatoid factor, extra-articular manifestations, and age at first occurrence of
      disease symptoms. CONCLUSIONS: NAT2 slow acetylation genotype may be a risk
      factor of individual susceptibility to RA.

PMID- 12235454
TI  - Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9
      genotypes.
AB  - OBJECTIVES: Our objective was to investigate the effects of genetic polymorphisms
      of cytochrome P450 (CYP) 2C9 on the pharmacokinetics of glyburide (INN,
      glibenclamide) and glimepiride, two widely used sulfonylurea antidiabetic drugs.
      METHODS: We conducted CYP2C9 genotyping for 29 healthy volunteers who had
      participated in our previous pharmacokinetic studies on glyburide or glimepiride.
      RESULTS: There were 17 subjects (59%) with the CYP2C9*1/*1 (wild-type) genotype,
      8 (28%) with the CYP2C9*1/*2 genotype, 3 (10%) with the CYP2C9*1/*3 genotype, and
      1 (3%) with the CYP2C9*2/*3 genotype. The pharmacokinetics of glyburide or
      glimepiride were not significantly changed among subjects with the CYP2C9*1/*2
      genotype. However, in individuals heterozygous for the CYP2C9*3 allele, the
      median total area under the plasma concentration-time curve of glyburide (n = 2)
      was 280% (P < or = .05) and that of glimepiride (n = 3) was 267% (P < or = .01)
      of the respective values in subjects with the CYP2C9*1/*1 genotype (n = 5 and n =
      12, respectively). Blood glucose responses to glyburide and glimepiride were not
      significantly affected by the CYP2C9 genotype. CONCLUSIONS: Genetic polymorphisms
      of CYP2C9 markedly affect the pharmacokinetics of both glyburide and glimepiride.
      The influence of the CYP2C9*3 variant allele on glyburide and glimepiride
      pharmacokinetics may be clinically significant.

PMID- 12235455
TI  - Pharmacokinetics of diltiazem and its metabolites in relation to CYP2D6 genotype.
AB  - OBJECTIVES: Recently, it was shown in vitro that the polymorphic enzyme
      cytochrome P450 (CYP) 2D6 mediates O-demethylation of diltiazem. The aim of this
      study was to compare the pharmacokinetics of diltiazem and its major metabolites
      in healthy human volunteers representing different CYP2D6 genotypes. METHODS:
      Norwegians of Caucasian origin were screened for their CYP2D6 genotype on the
      LightCycler (Roche Diagnostics, Mannheim, Germany) by melting-curve analysis of
      allele-specific fluorescence resonance energy transfer probes hybridized to
      polymerase chain reaction-amplified deoxyribonucleic acid. The first 5
      individuals identified with genotypes corresponding to a homozygous extensive,
      heterozygous extensive, or homozygous poor CYP2D6-metabolizing phenotype,
      respectively, were voluntarily enrolled in the pharmacokinetic study. The
      participants received diltiazem, 120 mg, as a single oral dose, and plasma
      samples were collected up to 24 hours after administration. Plasma samples were
      purified by solid phase extraction. Diltiazem and 7 phase I metabolites were
      analyzed by liquid chromatography-mass spectrometry. RESULTS: The
      pharmacokinetics of diltiazem was not significantly different between the
      subgroups. However, the systemic exposure of the pharmacologically active
      metabolites desacetyl diltiazem and N-demethyldesacetyl diltiazem was > or = 5
      times higher in poor CYP2D6 metabolizers than in extensive CYP2D6 metabolizers (P
      <.01). CONCLUSIONS: CYP2D6 activity does not have a major impact on the
      disposition of diltiazem. In contrast, desacetyl diltiazem and N
      demethyldesacetyl diltiazem are markedly accumulated in individuals expressing a
      deficient CYP2D6 phenotype. Because these metabolites exhibit pharmacologic
      properties of possible importance, individual CYP2D6 activity might be an aspect
      to consider in the clinical use of diltiazem.

PMID- 12235456
TI  - Ischemic stroke in a user of thermadrene: a case study in alternative medicine.
AB  - A case of a young user of Thermadrene (SportPharma USA, Inc, Concord, Calif), an
      herbal remedy for weight loss, was studied. We believe that Thermadrene can cause
      serious complications such as ischemic stroke. Because these remedies are
      available over the counter and are not regulated by the Food and Drug
      Administration or similar organizations, there is a need for critical scrutiny of
      their content and side effects, as is performed for other pharmaceuticals.

PMID- 12235458
TI  - Treatment of status epilepticus in children.
AB  - Status epilepticus is a medical emergency that requires prompt recognition and
      urgent treatment. Successful management of status epilepticus in children depends
      upon implementation of a treatment protocol modified according to current
      practices as well as availability of antiepileptic medications, out of hospital
      emergency services and intensive-care facilities. We propose a treatment protocol
      for status epilepticus in children in the Kingdom of Saudi Arabia.

PMID- 12235459
TI  - Acute retropharyngeal and parapharyngeal abscesses in children.
AB  - OBJECTIVE: Acute retropharyngeal and parapharyngeal abscess is a rare but serious
      disease in children. We reviewed our experience highlighting some of the unusual
      features of our cases. METHODS: Medical records of children less than 12-years
      old who were admitted to King Khalid University Hospital, Riyadh, Kingdom of
      Saudi Arabia, over a 10- year period with final diagnosis of deep neck infection,
      were reviewed. RESULTS: Eight patient's records were reviewed. Seven were less
      than 3-years of age. The retropharyngeal abscess was suspected clinically in 3
      cases only. The most common findings were fever, neck swelling and feeding
      problems. The duration of symptoms and signs were so variable. The most helpful
      diagnostic tests were direct visualization and computerized tomography scan of
      the cervical area. The combination of retropharyngeal and parapharyngeal abscess
      was encountered in 4 patients. Cefuroxime was the drug of choice in all patients.
      Five patients responded to conservative management with antibiotics alone. Two
      cases had unusual presentation, one with subacute neck swelling, and one with
      severe airway compromise one week after manipulation of the tonsils by
      traditional therapist. CONCLUSION: High index of suspicion is warranted in such
      rare and life threatening disease. Special attention should be directed to the
      parapharyngeal entity, which was not suspected clinically in any case. The use of
      traditional medicine could have serious consequences in some patients.

PMID- 12235460
TI  - Assessment of mother's knowledge and practice in use of oral rehydration solution
      for diarrhea in rural Bangladesh.
AB  - OBJECTIVE: To assess mothers' knowledge, attitude and use of oral rehydration
      solution (ORS) for diarrhea management at home, and feeding practices during
      diarrhea for children under 5-years of age, in a rural Health Development
      Project, Bangladesh. METHODS: This was a cross-sectional survey. This study was
      carried out in Cox's Bazar district, South Bangladesh, over a 2-week period,
      during May 1994. A sample of 300 households in the project area and a similar one
      in a control area were randomly selected using a multistage stratified technique.
      Data was collected by interviewing mothers at home using a standard questionnaire
      and through practical demonstration of how to prepare and use ORS correctly.
      Project and control households were compared regarding differences in knowledge
      and practice. RESULTS: More mothers in the project area received information
      regarding ORS than in the control area (63% versus 59%). The majority of mothers
      in both project and control areas recognized ORS packets (97% versus 95%). A
      significantly higher proportion of mothers in the project area knew how to
      prepare ORS correctly (64% versus 55%). Mothers' skill of using ORS was
      significantly associated with having seen a packet of ORS and mothers' education.
      The ORS use rate was lower in the project area compared with the control area
      (74% versus 84%). No significant differences in feeding practices during diarrhea
      were detected. CONCLUSION: The study showed that a significantly higher
      proportion of mothers in the project area knew how to prepare and use ORS
      correctly. However, the ORS use rate was inadequate. Repeated health education of
      mothers regarding diarrhea management is needed. Oral rehydration solution should
      be made available at health posts and households.

PMID- 12235461
TI  - Mothers' practices during pregnancy, lactation and care of their children in
      Riyadh, Saudi Arabia.
AB  - OBJECTIVE: To study mothers' practices during pregnancy, lactation and care
      during the first 2 years. METHODS: A cross section study was carried out in 5
      Primary Health Care Centres (PHCC) in Riyadh, Kingdom of Saudi Arabia. Two
      hundred and fifty women (50 from each PHCC) who have children less than 2-years
      of age who visited the selected PHCCs during the study period were selected by
      systematic random sampling. Data was collected via a questionnaire which
      contained sociodemographic characteristics of the mother and their children and
      mothers' practices during pregnancy, lactation and the care of their children.
      RESULTS: Approximately 73% of the mothers breast fed their children initially but
      only 37.6% are currently breast feeding their children. The majority of the
      mothers started breast feeding during 1-8 hours after delivery, 63% added
      supplementary foods to their children at 4-8 months. The majority of mothers
      visited antenatal clinics during pregnancy, vaccinated their children and
      followed up their children in well baby clinics. Half of the mothers are
      currently using contraceptives and 19% are consuming less food during pregnancy.
      The mothers' educational level was the most important factor associated with
      mothers' practices. CONCLUSION: Some mothers' practices during pregnancy,
      lactation and child care needs corrective intervention.

PMID- 12235462
TI  - Role of fine needle aspiration in diagnosing breast lesions.
AB  - OBJECTIVE: To determine the diagnostic efficacy of breast fine needle aspiration
      (FNA), using 72 cases that were having both FNA cytology and follow-up histology
      diagnosis. The study results were compared with results of 27 other studies in
      the literature. A review of literature regarding the additional benefits of
      performing "Triple Test" in increasing the cumulative diagnostic accuracy of FNA
      is also included. METHODS: Our study group consisted of 72 FNA cytologies of
      female breasts performed at our institution and followed by a histological
      diagnosis. The following parameters: Sensitivity, specificity, accuracy,
      predictive values, false positive and negative fraction rates were determined to
      establish the diagnostic efficacy of the breast FNA. RESULTS: The sensitivity of
      FNA procedure was 98.4% and specificity 60%, with the predictive value for
      positive diagnosis 93.9% and for negative diagnosis 85.7%. The overall diagnostic
      accuracy was 93%. The false positive fraction was 6% and the false negative
      fraction was 14.2%. The false positive and false negative cases were recorded as
      having a minimal effect on patient management, as all the false positive and
      negative diagnosis' were picked up at intra operative frozen sections, and hence
      no over or under treatment was given to the patients due to these FNA results.
      CONCLUSION: Fine needle aspiration breast biopsy is an efficient tool and yields
      a definitive diagnosis, and its use for routine diagnosis must be encouraged
      since it has high positive (93.9%) and negative (85.7%) predictive values.

PMID- 12235463
TI  - Efficacy of rifampicin plus doxycycline versus rifampicin plus quinolone in the
      treatment of brucellosis.
AB  - OBJECTIVE: The aim of this study was to compare the efficacy, tolerability and
      side effects of 2 treatment regimens for brucellosis. METHODS: Fifty-seven
      patients with brucellosis were followed up in our clinic. The patients were given
      rifampicin plus doxycycline or rifampicin plus quinolone. Thirty patients (group
      one) received rifampicin 600mg/daily plus doxycycline 100mg twice daily and 27
      patients (group 2) received quinolones (ofloxacin 200mg twice daily peroral) plus
      rifampicin 600mg/daily. Both regimens were administered for 45-days. During the
      course of treatment, patients were followed for the disappearance of physical
      signs and symptoms. All patients were followed up at least 6-months after
      cessation of therapy. Diagnosis of brucellosis was established by utilizing the
      following criteria; Isolation of brucella species in blood, body fluids (Sceptor,
      Becton-Dickinson, United States of America), compatible clinical picture
      supported by the detection of specific antibodies at significant titers or
      demonstration, or both, of an at least 4 fold rise in antibody titer in serum
      specimens taken after 2-weeks. Significant titer was determined to be >one/160 in
      the standart tube agglutination test (Brucella abortus Cromatest, Linear
      Chemicals, Spain). RESULTS: Of patients 14 (24.5%) were male and 43 (75.5%) were
      female. Mean age was 36.8   11.3 years (range 15-65). Sacroiliitis was the most
      common involvement in both groups 9 (30%) versus 6 (22%), followed by peripheral
      arthritis 6 (20%) versus 6 (22%). In this study, relapse rate was found 7.2% and
      6.7% for ofloxacin plus rifampicin and doxycycline plus rifampicin for a 6-week
      therapy (p>0.05). No significant adverse effects were associated with either
      combination. CONCLUSION: These results indicated that a 45-day course of
      doxycycline plus ofloxacin combination was as effective as the doxycycline plus
      rifampicin combination in patients with brucellosis.

PMID- 12235464
TI  - Evaluation of diagnosis of cutaneous leishmaniasis by direct smear, culture and
      histopathology.
AB  - OBJECTIVE: Definite diagnosis of cutaneous leishmaniasis is based on the
      isolation of the causative organism by smear and culture or its identification in
      tissue section. This study was conducted to evaluate the efficacy of different
      sampling techniques. These techniques are tissue sampling with dental broach,
      slit scrape method, aspiration of the lesion edge and biopsies. METHODS: This
      study was carried out in the Department of Dermatology, Baghdad Teaching
      Hospital, Baghdad, Iraq. Sixty patients with cutaneous leishmaniasis were seen,
      33 females and 27 males with a mean age of 15.7 years and the mean duration of
      the lesions was 8-weeks. The total number of lesions was 167, 60% ulcerative and
      40% nodular, 40% of patients had single lesion, while 60% had multiple lesions,
      and the highest number being 11 lesions. Smears and cultures were carried out in
      all patients using different sampling techniques. Biopsies were taken from 20
      patients. RESULTS: It was found that tissue sampling using dental broach was
      better than the other smearing techniques. It was positive in 71.5% while culture
      on Nicolle-Novy-MacNeal media was positive in 80% of cases and these figures were
      much higher in comparison to other published studies. The morphology of LD bodies
      (amastigotes) in smears was mainly spindle shape, other morphological forms like
      barrel, safety pin and umbrella like were noticed, while the morphology in
      histopathological sections were rounded with a nucleus and kinetoplast. However,
      in some sections spindle shape form similar to smear morphology were detected. LD
      bodies were seen in histopathological sections in 30% of patients. Other
      histopathological features were mainly abundance of lymphocytes and plasma cells
      in the wet ulcerative lesions while in dry nodular types there was a tendency to
      form granuloma with less lymphocytes and scanty plasma cells. CONCLUSION: Tissue
      sampling using dental broach appeared to be more efficient than other sampling
      techniques used in this study. Histopathological sections have identified the
      focal presence of the parasites. Thus, multiple site samples from the edge of the
      lesions are needed.

PMID- 12235465
TI  - Lamivudine in chronic hepatitis B virus.
AB  - OBJECTIVE: To access the effect of one year treatment with Lamivudine, and its
      durability on patients with compensated chronic hepatitis B. METHODS: Thirty-six
      patients with hepatitis B surface antigen positive, hepatitis B virus
      deoxyribonucleic acid (DNA) positive, were treated with 100 mg Lamivudine daily
      for one year, irrespective of their liver enzymes level, alanine aminotransferase
      or hepatitis B envelope antigen status. Patients with normal alanine
      aminotransferase and negative hepatitis B virus DNA at the end of the treatment
      were responders and those with persistent response 16 weeks off treatment were
      considered having durable response. RESULTS: Three patients dropped out and 33
      patients completed the study. Eight patients (24.2%) had normal alanine
      aminotransferase, 25 patients (75.8%) had increased alanine aminotransferase.
      Thirty patients (90.9%) were hepatitis B envelope antigen negative. Two patients
      (25%) with initial normal alanine aminotransferase and 7 patients (28%) with
      increased enzyme level, responded at end of treatment. One patient with positive
      hepatitis B envelope antigen responded to treatment. Only one patient relapsed
      during follow-up period off treatment. CONCLUSION: Lamivudine is associated with
      durable response in patients with hepatitis B virus and negative hepatitis B
      envelope antigen. Longer treatment for more than one year may be required to
      improve response rates.

PMID- 12235466
TI  - Effects of short term metformin administration on androgens in normal men.
AB  - OBJECTIVE: To study the effect of metformin on androgens in normal men. METHODS:
      A total of 12 healthy males volunteered to participate in the study. A blood
      sample was obtained from each of them and analyzed for the following:
      Testosterone (total and free), sex hormone binding globulin
      dehydroepiandrosterone sulphate, 17-hydroxyprogesterone, luteinizing hormone, and
      follicle stimulating hormone. In addition, each participant was subjected to a
      glucose tolerance test and his insulin level was measured. Metformin 850 mg twice
      daily for 2-weeks was given to each subject after which the above tests were
      repeated. A paired t-test was used to assess the statistical significance of any
      observed differences before and after metformin. RESULTS: After metformin
      administration, there was a significant reduction in serum level of total
      testosterone (p=0.0001), free testosterone (P=0.002), and 17 hydroxyprogesterone
      (p=0.0001). There was also a significant increase in serum level of sex hormone
      binding globulin (p=0.009) and dehydroepiandrosterone sulphate (P=0.0008). Serum
      levels of luteinizing hormone and follicle stimulating hormone showed no
      significant changes. Similarly, there were no changes in fasting plasma glucose,
      fasting serum insulin, weight, or blood pressure. CONCLUSION: Metformin
      administration was associated with a reduction in total testosterone, free
      testosterone, and 17-hydroxyprogesterone and an increase in sex hormone binding
      globulin and dehydroepiandrosterone sulphate in normal males. The clinical
      significance of these findings needs further investigation.

PMID- 12235467
TI  - Radiographic osteoarthritis and obesity.
AB  - OBJECTIVE: To determine the association between obesity and radiographic
      osteoarthritis (OA) of the knee and generalized OA. METHODS: A cross-sectional
      survey of patients attending 14 primary clinics for a variety of medical
      complaints was conducted. They were consented, interviewed, examined and
      radiographed for the presence of knee and generalized OA. The association between
      OA and weight was then assessed. This study was carried out in 14 primary care
      clinics in North Riyadh, Kingdom of Saudi Arabia, between September 1998 through
      to March 1999. RESULTS: Two hundred and nineteen patients (118 males, 101
      females) completed the study and their results were analyzed. We found a strong
      association between excess weight and knee OA in females [overall ratio (OR) 3.28
      (95% confidence intervals (CI), 2.07-5.36)] and a weaker link with knee OA in
      males [OR 1.88 (95% CI, 1.24-2.92)]. Generalized OA was found to be associated
      with obesity in females only [OR 1.93 (95% CI, 1.09-3.43)]. Reporting of joint
      symptoms in patients with radiographic knee OA was also associated with obesity
      (P=0.0001). CONCLUSION: Excess weight is strongly associated with knee OA in
      females and symptoms of joint pain in all OA patients, with a weaker but still
      significant link with male knee OA and generalized OA in females.

PMID- 12235468
TI  - The inter-relationship hematological parameters between Saudi newborns and
      parents.
AB  - OBJECTIVE: To determine the relationship of the hematological parameters between
      Saudi newborns and their parents. METHODS: This study was carried out at King
      Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia, over a one-year
      period. Venous blood samples were taken from 82 healthy Saudi pregnant women in
      labor at full term, their husbands, and umbilical cord blood after delivery.
      Estimation of the hematological indices, in addition to transferrin level were
      performed. RESULTS: A statistically significant correlation was found between
      parents and cord blood with regards to red blood count, mean corpuscular volume,
      mean corpuscular hemoglobulin, mean corpuscular hemoglobulin concentration and
      packed cell volume, while no correlation was found with hemoglobulin and
      transferrin. CONCLUSION: Some of the hematological indices could be mainly
      genetically determined including red blood count, mean corpuscular volume, mean
      corpuscular hemoglobulin concentration, and packed cell volume as significant
      correlation was found between parents and their newborns while hemoglobulin and
      transferrin levels were not as these variables are mainly affected by
      environmental factors.

PMID- 12235469
TI  - Incidence of differentiated cancer in nodular goiter.
AB  - OBJECTIVE: The study aims to determine the incidence of differentiated thyroid
      cancer in surgically treated thyroid nodules and to study its clinical and
      pathological aspect. The objective was to formulate a uniform departmental policy
      for the most appropriate surgical management of this potentially curable disease.
      METHODS: This is a prospective clinicopathological study carried out at the
      Department of General Surgery, Riyadh Medical Complex, Riyadh, Kingdom of Saudi
      Arabia, from January 1996 through to December 2000. A total of 483
      thyroidectomies were performed. Preoperative diagnosis of thyroid cancer was
      based on clinical and fine needle aspiration cytology (FNAC). The patients were
      identified as low risk and high risk groups for surgical treatment. The
      histopathological diagnosis of differentiated thyroid cancer was confirmed in 103
      patients (21.3%). The medical records of all these patients were reviewed for
      age, sex, clinical presentation, investigations and outcome of surgery. RESULTS:
      A total of 103 patients (21.3%) with histopathologically confirmed differentiated
      thyroid cancer were studied. The female to male ratio was 4:1. The mean age was
      36.7 years. Sixty-five percent of patients were between 21-40 years. Nodular
      goiter was the most frequent presentation observed in 78.6% cases. Fine needle
      aspiration cytology was suggestive of malignancy in 86.4% cases. Most of the
      patients (84.5%) were identified as low-risk. Papillary carcinoma was the most
      common tumor (89%) followed by follicular cancer (8.7%). Eight percent of
      patients had cervical lymph node involvement at presentation. Total lobectomy was
      performed in 50.5% and total thyroidectomy in an additional 29% of patients.
      Overall operative morbidity was 6.8% with zero mortality. Two (1.9%) patients
      presented with ipsilateral lymph node recurrence with mean follow up of 26.5
      months and underwent limited neck dissection. CONCLUSION: The relatively high
      incidence of differentiated thyroid cancer in surgically treated nodular is
      attributed to increased confidence in FNAC and careful patient selection. Total
      lobectomy with isthmusectomy for low risk and total thyroidectomy for high risk
      patients may be recommended as the preferred treatment modalities.

PMID- 12235470
TI  - Levels of maximum end-expiratory carbon monoxide and certain cardiovascular
      parameters following hubble-bubble smoking.
AB  - OBJECTIVE: The physiological effects of cigarette smoking have been widely
      studied, however, little is known regarding the effects of smoking hubble-bubble.
      We examined the acute effects of hubble-bubble smoking on heart rate, systolic,
      diastolic, and mean arterial blood pressure and maximum end-expiratory carbon
      monoxide. METHODS: This study was carried out in the student laboratory, School
      of Medicine, Department of Physiology, University of Jordan, Amman, Jordan,
      during the summer of 1999. In 18 healthy habitual hubble-bubble smokers, heart
      rate, blood pressure, and maximum end-expiratory carbon monoxide was measured
      before, during and post smoking of one hubble-bubble run (45 minutes). RESULTS:
      Compared to base line (time zero), at the end of smoking heart rate, systolic
      blood pressure, diastolic blood pressure, mean arterial blood pressure, and
      maximum end-expiratory carbon monoxide were increased 16   2.4 beats per minute,
      6.7   2.5 mm Hg, 4.4   1.6 mm Hg, 5.2   1.7 mm Hg, and 14.2   1.8 ppm, (mean  
      standard error of mean, P<.05). CONCLUSION: Acute short-term active hubble-bubble
      smoking elicits a modest increase in heart rate, systolic blood pressure,
      diastolic blood pressure, mean arterial blood pressure and maximum end-expiratory
      carbon monoxide in healthy hubble-bubble smokers.

PMID- 12235471
TI  - Influence of age, sex, folate and vitamin B12 status on plasma homocysteine in
      Saudis.
AB  - OBJECTIVE: To evaluate the reference intervals for fasting total plasma
      homocysteine concentrations in Saudi healthy males and females in relation to
      age, sex and the nutritional status of folate and vitamin B12. METHODS: A
      prospective study was conducted on randomly selected Saudi healthy males (n=642)
      and females (n=784) living in the Jeddah area, Kingdom of Saudi Arabia. Plasma
      homocysteine together with serum folate and plasma vitamin B12 concentrations
      were determined. Analysis of variance was used to examine differences among
      various groups according to age, sex or folate, or both or vitamin B12 status for
      different variables. Correlations were carried out using multiple linear
      regression analysis. RESULTS: Reference intervals for plasma homocysteine
      concentrations in Saudi healthy males and females (age 20 -69 years) was
      documented. The age-adjusted geometric mean of plasma homocysteine concentration
      was significantly greater in males (9.91 micromol/L) than in females (8.08
      micromol/L) (P<0.0001). In both males and females, values for serum folate and
      plasma vitamin B12 concentrations significantly and negatively correlated with
      plasma homocysteine concentrations (P<0.000). Serum total cholesterol showed
      significant positive correlations with plasma homocysteine in both males
      (r=0.448, P<0.000) and females (r=0.313; P < 0.000). Diastolic (r= 0.182;
      P<0.001) and systolic (r=0.309; P < 0.000) blood pressure values showed
      significant positive correlations with plasma homocysteine concentrations in
      females only. Stepwise multiple linear regression analysis showed that in both
      males and females, age, sex, serum folate, and waist-to-hip ratio and plasma
      vitamin B12 were significant determinants of plasma homocysteine concentrations.
      CONCLUSION: The first data on plasma homocysteine concentrations in Saudi healthy
      males and females are reported. Age and sex differences were confirmed and a
      significant inverse relationship between plasma homocysteine concentrations and
      that of serum folate and plasma vitamin B12 was observed. Various independent
      variables including age, sex, serum folate, waist-to-hip ratio and plasma vitamin
      B12 contributed to the changes in plasma homocysteine. Plasma homocysteine
      concentrations should be evaluated in patients at risk for cardiovascular and
      other related diseases in the Saudi population.

PMID- 12235472
TI  - Compliance with appointments and medications in a pediatric neurology clinic at a
      University Hospital in Riyadh, Saudi Arabia.
AB  - OBJECTIVE: The objectives of the study are to estimate the rate of epileptic
      patients' compliance with appointments and medications in a pediatric neurology
      clinic. Also to study the factors associated with non-compliance and to determine
      the parents' perceived reasons for non-compliance with appointments. METHODS: It
      is a prospective study in which 147 epileptic children who attended the neurology
      clinic during the first 12-months of the study period were included. Patients
      were recruited into the study after their parents were interviewed using a
      detailed questionnaire; their compliance with appointments was monitored
      prospectively over at least a one year from their recruitment into the study. The
      parents of the other 70 patients who did not attend the clinic were telephoned.
      Only 32 replied and were asked about the reasons for non-attendance to the
      clinic. RESULTS: Eighty-six percent of the patients' parents stated that they
      were complying with the medications while only 53% of them did not miss any
      appointment to the clinic during the study period. Compliers with appointments
      were more likely to comply with their medications too. Children with grand-mal
      epilepsy and absence seizures were found to be more likely to comply with taking
      medications than patients with febrile, rolandic and myoclonic seizures (P=0.01).
      Health belief model factors associated with non-compliance were 1. Children
      encountering side effects from their medications 2. Parents who were not
      satisfied with the provided services 3. Parents who thought that alternative
      medicine is more effective than traditional medicine 4. Parents who think that
      their children are not susceptible. Patients' perceived main reasons for non
      compliance were wrongly registered appointments (27.5%), forgetfulness (22.5%)
      and busy parents. CONCLUSION: Failure to keep the clinic appointment is an
      indicator of poor compliance with medications. A telephone call is recommended to
      reduce the role of clinic non-compliance. Developing a questionnaire form to
      investigate parents health belief model could be used routinely by social workers
      and then health education could be tailored for each patient and parent.

PMID- 12235473
TI  - Prosthetic dental treatment needs in Eastern [corrected] Saudi Arabia.
AB  - OBJECTIVE: The objective of this study was to determine the prosthetic treatment
      needs of an adult population in Al-Ahsa Area, Kingdom of Saudi Arabia. METHODS: A
      sample of adults attending the King Fahad Hospital Dental Center, Al-Ahsa,
      Kingdom of Saudi Arabia were examined for prosthetic treatment needs utilizing
      the World Health Organization criteria during 1999. Statistical analysis system
      was utilized to generate frequencies, means and standard deviations, and various
      statistical tests were carried out. RESULTS: A total of 435 adults, 192 (44.1%)
      males and 243 (55.9%) females with a mean age of 47.7 (standard deviation 15.4)
      years were examined for prosthetic treatment needs. About two-thirds (64.8%) of
      the sample were in need of an upper denture. A significantly higher number of
      males (68.8%) needed an upper denture as compared to the females (61.7%). About
      three-quarters (73.8%) of the sample were in need of a lower denture. The need
      for lower denture was similar among the males (75.0%) and females (72.8%). About
      one-sixth (17.2%) of the sample was in need of an upper bridge. A higher number
      of females (18.9%) needed an upper bridge as compared to the males (15.1%). About
      one-quarter (22.5%) of the sample was in need of a lower bridge. A higher number
      of females (25.5%) needed lower bridge as compared to the males (18.8%). The need
      for upper denture was similar in both urban (64.7%) and rural (65.1%) dwellers.
      The need for lower denture was also similar in both urban (73.2%) and rural
      (75.2%) dwellers. A higher number of rural dwellers needed an upper (20.2%) and
      lower (26.4%) bridge as compared to the upper (16%) and lower (20.9%) bridge in
      urban dwellers. CONCLUSION: The results indicate that more than one- quarter of
      the sample needs a denture. A significantly higher number of males needed
      dentures than females. More females were in need of a bridge as compared with
      males. A significantly higher percentage of urban population needed full dentures
      as compared with rural population.

PMID- 12235474
TI  - Satisfaction with physiotherapy among patients at a general hospital in Kuwait.
AB  - OBJECTIVE: A pilot survey was conducted with adult patients attending the
      Physiotherapy Department at the Farwaniah Hospital, Kuwait, during the year 2000,
      to validate a questionnaire measuring outpatients' satisfaction with different
      aspects of physiotherapy care and associated socio-demographic factors. METHODS:
      This study was carried out in the Department of Physiotherapy, Farwaniah
      Hospital, State of Kuwait, during a time period of 5-months. A structured
      questionnaire was developed to include questions relating to ease of contact for
      appointments, the organizational settings, quality of therapeutic services,
      overall satisfaction with the department, and willingness to re-utilize or to
      recommend the department in the future, along with socio-demographic data and the
      duration of the disease. RESULTS: A total of 144 questionnaires were completed by
      a group of mostly women (64%) married (70%) participants, with a mean age of 40
      years. Kuwaitis were 59% of the group, and less than 50% had a secondary
      education or more. A vast majority of participants perceived the department was
      easy to contact. Those with lower such perception were relatively older patients.
      On all other dimensions of satisfaction, the response was generally positive,
      regardless of socio-demographic variables or duration of disease. Less educated
      patients had a slightly lower tendency to recommend the department in the future
      (51%) than more educated ones (60%). CONCLUSION: Patients in Kuwait tend to
      express high levels of satisfaction with health services, an attitude, which may
      be biased by cultural reluctance to express public negative views. Alternatively,
      it may be influenced by the relatively sustained interaction between patients and
      their therapists. It is important to provide more orientation to older, less
      educated patients who may feel lost within a process they do not fully
      comprehend.

PMID- 12235475
TI  - Attitudes to premarital counseling among students of Abha Health Sciences
      College.
AB  - OBJECTIVE: The aim of this study is to explore the attitudes of the students of
      Health Sciences College in Abha, Kingdom of Saudi Arabia (KSA) towards premarital
      counseling. METHODS: This study was conducted among the students of Health
      Sciences Colleges in Abha, KSA, during the 2nd semester of the academic year of
      1999-2000. A self-administered questionnaire was distributed to all available
      students who answered it under the direct supervision of the Heads of
      Departments. The questionnaire consisted of 3 main parts; the first part was
      regarding socio-demographic and scientific characteristics, the 2nd part
      concerned with attitudes towards premarital counseling while the 3rd part
      explored the preferred items to be included in premarital counseling. Data of the
      questionnaire were entered and analyzed by statistical package for social
      sciences. Association between categorical variables were tested by Chi-square
      test and considered significant if (P-value less than 0.05). RESULTS: One hundred
      and eighty-six students responded, giving a response rate of 70%. Seventy percent
      of students showed acceptance of premarital counseling while 13% rejected it.
      Legalization of premarital counseling was agreed on by 19% compared to 41% who
      refused it. Family history and blood tests for hemoglobinopathies were the most
      common 2 items preferred to be included in premarital counseling by the
      respondents. CONCLUSION: This study showed that most of the students at Health
      Sciences College in Abha, KSA have good attitudes towards premarital counseling
      in spite of a few students who justify their refusal by the misunderstanding of
      Islamic rules. This misunderstanding needs intensification of health education in
      which religious leaders are involved to clarify and correct this misconception.

PMID- 12235476
TI  - Deficiencies of history taking among medical students.
AB  - OBJECTIVE: This study was designed to identify the deficiencies of the history
      taken by final medical students at the University of Bahr Elghazal, Khartoum,
      Sudan, during the academic year 2000 through to 2001. METHODS: Throughout the
      academic year the author observed the students while taking history. Each student
      was asked to give a fully written case history. I assessed the basic skills of
      history taking (questioning, facilitation, clarification, jargon use, initiation
      of interview and keeping to time limits). I also assessed the amount and accuracy
      of data obtained. The findings were rated on a 3-point scale (good, fair, poor).
      RESULTS: For the 45 students assessed, the deficiencies of history taking
      obtained included poor questioning (66.6%), poor facilitation (51.1%), poor
      clarification (40%), use or acceptance of jargons (42.2%), failure of proper
      initiation of interview (37.8%), failure of keeping to time limits (33.3%),
      failure of identification of major symptoms (33.3%), poor analysis of symptoms
      (53.3%), lack of control of the interview (31.1%), poor elucidation of previous
      events (48.9%) and poor coverage of social aspects (62.2%). CONCLUSION: The
      history obtained by our medical students is deficient and they generally lack the
      basic skills of interviewing. Many factors contribute to this, (namely deficient
      training, lack of staff and deficit of teaching hospitals). The author discussed
      possible solutions to remedy the history taking deficiencies.

PMID- 12235477
TI  - Ruptured sinus of Valsalva.
AB  - This case report is about a 24-year-old lady, labeled case of ventricular septal
      defect since birth, who presented with sudden onset of chest pain and palpitation
      followed by acute pulmonary edema. She was found to have clinical cardiomegaly,
      biventricular impulse, pansystolic murmur of ventricular septal defect with
      continuous murmur at the right lower sternal border. Electrocadiogram revealed
      frequent ventricular premature beat and chest skiagram revealed cardiomegaly with
      pulmonary venous congestion. Transthoracic color doppler echocardiography
      revealed ruptured non coronary sinus of valsalva to right ventricle with large
      left to right shunt, perimembraneous sub aortic ventricular septal defect with
      left to right shunt and prolapse of right coronary cusp with mild aortic
      regurgitation and good left ventricular systolic function. She underwent
      corrective surgery of ruptured sinus of valsalva and ventricular septal defect
      and aortic valve replacement.

PMID- 12235478
TI  - Retroperitoneal abscess as an initial presentation of cecal carcinoma.
AB  - We report an unusual case of cecal carcinoma presenting first time as
      retroperitoneal abscess. As the patient was septic on presentation and the
      underlying cancer was not clear, she was treated initially by extraperitoneal
      drainage of the abscess. She later underwent a palliative right hemicolectomy.
      She presented a month later with recurrence at the drainage site. This case
      highlights this unusual initial presentation of right colonic cancer, the
      diagnostic dilemma and the poor prognosis associated with it.

PMID- 12235479
TI  - Cold cellulitis. An unusual presentation of cutaneous leishmaniasis.
AB  - We describe a case of cutaneous leishmaniasis, which presented as what we call
      "cold cellulitis". This may be differentiated from classical
      cellulitis/erysipelas by 1. Lesser local reaction like pain and tenderness 2. No
      systemic symptoms 3. No leucocytosis 4. Negative bacteriological and serological
      assay for bacterial cellulitis/erysipelas, 5. Longer course of illness and 6.
      Failure to respond to antibiotics. However, awareness of this type and frequent
      skin smears or skin biopsy will settle the right diagnosis. A review of different
      leishmanial presentations is given for comparison.

PMID- 12235480
TI  - The congenital absence of the radius, scaphoid, trapezium, thumb and hypoplasia
      of the lunate.
AB  - The congenital absence of the right radius, scaphoid, trapezium, thumb and
      hypoplasia of the lunate are described in a 9-year-old boy. He had full extension
      of his elbow, while flexion motion was limited to 90 degrees. His hand was
      radially deviated. The thumb was absent. The index and middle fingers were united
      and immobile. The ring finger had movement only at the metacarpophalangeal joint,
      while the little finger had full motion. Complete blood count fell within normal
      ranges. He had no other malformations or mental retardation. No hereditary family
      history was found and there was no consanguineous marriage. This case is
      different from cases mentioned in the literature due to lunate hypoplasia and the
      anomalies of the index, middle and ring fingers.

PMID- 12235481
TI  - Transabdominal cervicoisthmic cerclage after multiple failed vaginal cerclages.
AB  - Cervical incompetence is a condition traditionally treated by cervical cerclage.
      We describe a patient who had 6 failed cervical cerclages and who was treated
      with transabdominal cervicoisthmic cerclage. There were no intra-operative or
      post-operative complications and the patient was regularly reviewed in the
      antenatal clinic by a senior physician and with a series of transvaginal
      ultrasounds. The patient went into labor at 36-weeks of gestation and had an
      emergency lower segment cesarean section, with a live male infant weighing 2.38
      kg. Both mother and baby did well after delivery.

PMID- 12235482
TI  - Clinical uses of e-mail.

PMID- 12235483
TI  - Pityriasis lichenoides et varioliformis acuta in pregnancy. Does it affect
      pregnancy outcome?

PMID- 12235484
TI  - Syncollin homo-oligomers associate with lipid bilayers in the form of doughnut
      shaped structures.
AB  - Syncollin is a 16-kDa protein that is associated with the luminal surface of the
      zymogen granule membrane in the pancreatic acinar cell. Detergent-solubilized,
      purified syncollin migrates on sucrose density gradients as a large (120-kDa)
      protein, suggesting that it exists naturally as a homo-oligomer. In this study,
      we investigated the structure of the syncollin oligomer. Chemical cross-linking
      of syncollin produced a ladder of bands, the sizes of which are consistent with
      discrete species from monomers up to hexamers. Electron microscopy of negatively
      stained syncollin revealed doughnut-shaped structures of outer diameter 10 nm and
      inner diameter 3 nm. Atomic force microscopy (AFM) of syncollin on mica supports
      at pH 7.6 showed particles of molecular volume 155 nm(3). Smaller particles were
      observed either at alkaline pH (11.0), or in the presence of a reducing agent
      (dithiothreitol), conditions that cause dissociation of the oligomer. AFM imaging
      of syncollin attached to supported lipid bilayers again revealed doughnut-shaped
      structures (outer diameter 31 nm, inner diameter 6 nm) protruding 1 nm from the
      bilayer. Finally, addition of syncollin to liposomes rendered them permeable to
      the water-soluble fluorescent probe 5(6)-carboxyfluorescein. These results are
      discussed in relation to the possible physiological role of syncollin.

PMID- 12235485
TI  - Modeling light-induced currents in the eye of Chlamydomonas reinhardtii.
AB  - Rhodopsin-mediated electrical events in green algae have been recorded in the
      past from the eyes of numerous micro-algae like Haematococcus pluvialis,
      Chlamydomonas reinhardtii and Volvox carteri. However, the electrical data
      gathered by suction-pipette techniques could be interpreted in qualitative terms
      only. Here we present two models that allow a quantitative analysis of such
      results: First, an electrical analog circuit for the cell in suction pipette
      configuration is established. Applying this model to experimental data from
      unilluminated cells of C. reinhardtii yields a membrane conductance of about 3
      Sm(-2). Furthermore, an analog circuit allows the determination of the
      photocurrent fraction that is recorded under experimental conditions. Second, a
      reaction scheme of a rhodopsin-type photocycle with an early Ca(2+) conductance
      and a later H(+) conductance is presented. The combination of both models
      provides good fits to light-induced currents recorded from C. reinhardtii.
      Finally, it allowed the calculation of the impact of each model parameter on the
      time courses of observable photocurrent and of inferred transmembrane voltage.
      The reduction of the flash-to-peak times at increasing light intensities are
      explained by superposition of two kinetically distinct rhodopsins and by assuming
      that the Ca(2+)-conducting state decays faster at more positive membrane
      voltages.

PMID- 12235486
TI  - A new level detector for ion channel analysis.
AB  - The algorithm proposed here for automatic level detection in noisy time series of
      patch-clamp current is based on the detection of jump-free sections in the time
      series. The detector moves along the time series and uses a chi(2) test for the
      detection of jumps. When a jump is detected, the mean value, the variance and the
      length of the preceding jump-free section are stored. A Student's t-test was
      employed for the assignment of detected jump-free sections to discrete levels of
      the Markov model and for rejection of all sections with multiple assignments. The
      choice of the two significance levels is based on a 3-D diagram displaying the
      average number of detected levels from several time series vs. the significance
      levels of jump detection and of level assignment. The correct one is selected out
      of several plateaus with integer number of levels by means of the criterion of
      minimum scatter or other plausibility considerations. The test has been applied
      to simulated data obtained from a 2-state model and a 5-state aggregated Markov
      model, and the influences of SNR and of gating frequency are shown. Finally, the
      performance of the level detector is compared with a fit-by-eye and with a fit of
      the amplitude histogram by a sum of gaussians. At high noise, the fit of
      amplitude histograms failed, whereas the other two approaches were about equal.

PMID- 12235487
TI  - Kinetically different populations of O-pyromellityl-gramicidin channels induced
      by poly-L-lysines in lipid bilayers.
AB  - Clustering of membrane proteins, in particular of ion channels, plays an
      important role in their functioning. To further elucidate the mechanism of such
      ion channel activity regulation, we performed experiments with a model system
      comprising the negatively-charged gramicidin analog, O-pyromellitylgramicidin
      (OPg) that forms ion channels in bilayer lipid membrane (BLM), and polycations.
      The effect of polylysines on the kinetics of OPg channels in BLM was studied by
      the method of sensitized photoinactivation. As found in our previous work, the
      interaction of polylysine with OPg led to the deceleration of the OPg
      photoinactivation kinetics, i.e., to the increase in the characteristic time of
      OPg photoinactivation. It was shown here that in a certain range of polylysine
      concentrations the photoinactivation kinetics displayed systematic deviations
      from a monoexponential curve and was well described by a sum of two exponentials.
      The deviations from the monoexponential approximation were more pronounced with
      polylysines having a lower degree of polymerization. These deviations increased
      also upon the elevation of the ionic strength of the bathing solution and the
      addition of calcium ions. A theoretical model is presented that relates the OPg
      photoinactivation kinetics at different concentration ratios of OPg and
      polylysine to the distribution of OPg molecules among OPg-polylysine clusters of
      different stoichiometry. This model is shown to explain qualitatively the
      experimental results, although the quantitative description of the whole body of
      evidence requires further development, assuming that the interaction of
      polylysine with OPg causes segregation of membrane domains enriched in OPg
      channels. The single-channel data, which revealed the insensitivity of the single
      channel lifetime of OPg to the addition of polylysine, are in good agreement with
      the theoretical model.

PMID- 12235488
TI  - Altered channel properties of porins from Haemophilus influenzae: isolates from
      cystic fibrosis patients.
AB  - Changes in amino-acid sequence of the unique pore-forming protein of H.
      influenzae (OmpP2; porin) have been associated with increased antimicrobial
      resistance in H. influenzae strains isolated from cystic fibrosis patients. From
      patients who were subjected to long-term antimicrobial therapy, H. influenzae
      strains 67d and 69a (patient 27) and strains 77a and 77f (patient 30) were
      isolated. Strains 67d and 77a were previously shown to have elevated values for
      minimal inhibitory concentrations of antibiotics compared to strains 69a and 77f.
      Porins were extracted from all four H. influenzae strains by detergent treatment
      and purified to homogeneity by ion exchange chromatography. By reconstitution of
      the clinical Hi porins into planar lipid bilayers, single-channel conductance,
      ionic selectivity, and voltage-gating characteristics were assessed. Porins 77a
      and 77f displayed similar single-channel conductance and ionic selectivity.
      Current-voltage relationships were determined for the different porins: porin 77f
      displayed substantial voltage gating at both positive and negative polarity;
      porin 77a gated at negative polarity only. Porins 67d and 69a showed substantial
      differences in their pore-forming properties: the single-channel conductance of
      porin 69a was significantly increased (1.05 nS) relative to porin 67d (0.73 nS).
      Porin 67d was twice as permeable to cations as porin 69a, and at both positive
      and negative polarities the extent of voltage gating was greater for porin 67d
      relative to porin 69a. Expression of the porins in an isogenic, porin-deleted H.
      influenzae background allowed for assessment of the contribution of each porin to
      the minimum inhibitory concentrations of various antimicrobial compounds. Porin
      67d was found to have a decreased susceptibility to the antimicrobials novobiocin
      and streptomycin. This decreased susceptibility of porin 67d to novobiocin and
      streptomycin correlates with its decrease in single-channel conductance.

PMID- 12235489
TI  - Electrolyte transport in the mouse trachea: no evidence for a contribution of
      luminal K(+) conductance.
AB  - Recent studies on frog skin acini have challenged the question whether Cl(-)
      secretion or Na(+) absorption in the airways is driven by luminal K(+) channels
      in series to a basolateral K(+) conductance. We examined the possible role of
      luminal K(+) channels in electrolyte transport in mouse trachea in Ussing-chamber
      experiments. Tracheas of both normal and CFTR (-/-) mice showed a dominant
      amiloride-sensitive Na+ absorption under both, control conditions and after cAMP
      dependent stimulation. The lumen-negative transepithelial voltage was enhanced
      after application of IBMX and forskolin and Cl(-) secretion was activated.
      Electrolyte secretion induced by IBMX and forskolin was inhibited by luminal
      glibenclamide and the blocker of basolateral Na(+2)Cl(-)K(+) cotransporter
      azosemide. Similarly, the compound 293B, a blocker of basolateral KCNQ1/KCNE3
      K(+) channels effectively blocked Cl(-) secretion when applied to either the
      luminal or basolateral side of the epithelium. RT-PCR analysis suggested
      expression of additional K(+) channels in tracheal epithelial cells such as Slo1
      and Kir6.2. However, we did not detect any functional evidence for expression of
      luminal K(+) channels in mouse airways, using luminal 293B, clotrimazole and
      Ba(2+) or different K(+) channel toxins such as charybdotoxin, apamin and a
      dendrotoxin. Thus, the present study demonstrates Cl(-) secretion in mouse
      airways, which depends on basolateral Na(+2)Cl(-)K(+) cotransport and luminal
      CFTR and non-CFTR Cl(-) channels. Cl(-) secretion is maintained by the activity
      of basolateral K(+) channels, while no clear evidence was found for the presence
      of a luminal K(+) conductance.

PMID- 12235490
TI  - Modifications of human cardiac sodium channel gating by UVA light.
AB  - Voltage-gated Na(+) channels are membrane proteins responsible for the generation
      of action potentials. In this report we demonstrate that UVA light elicits gating
      changes of human cardiac Na+ channels. First, UVA irradiation hampers the fast
      inactivation of cardiac Nav1.5 Na(+) channels expressed in HEK293t cells. A
      maintained current becomes conspicuous during depolarization and reaches its
      maximal quasi steady-state level within 5-7 min. Second, the activation time
      course is slowed by UVA light; modification of the activation gating by UVA
      irradiation continues for 20 min without reaching steady state. Third, along with
      the slowed activation time course, the peak current is reduced progressively.
      Most Na(+) currents are eliminated during 20 min of UVA irradiation. Fourth, UVA
      light increases the holding current nonlinearly; this phenomenon is slow at first
      but abruptly fast after 20 min. Other skeletal muscle Nav1.4 isoforms and native
      neuronal Na(+) channels in rat GH(3) cells are likewise sensitive to UVA
      irradiation. Interestingly, a reactive oxygen metabolite (hydrogen peroxide at
      1.5%) and an oxidant (chloramine-T at 0.5 mM) affect Na(+) channel gating
      similarly, but not identically, to UVA. These results together suggest that UVA
      modification of Na(+) channel gating is likely mediated via multiple reactive
      oxygen metabolites. The potential link between oxidative stress and the impaired
      Na(+) channel gating may provide valuable clues for ischemia/reperfusion injury
      in heart and in CNS.

PMID- 12235491
TI  - Anderson-Fabry disease with cerebrovascular complications in two Italian
      families.
AB  - We describe four patients with cerebrovascular complications from two unrelated
      Italian families with Anderson-Fabry disease. Clinical examination, neuroimaging
      (MRI), biochemical and genetic analyses were carried out in all the patients.
      Alpha-galactosidase A activity was detected by fluorimetric assay and genetic
      analysis was performed by DNA sequencing. Family 1. A male patient presented
      recurrent strokes when he was 34 years old, albuminuria and subsequently
      progressive renal failure to renal transplantation. Family 2. A male patient,
      aged 32 years, had diplopia for a few days and then recurrent strokes with left
      spastic hemiparesis and internuclear ophthalmoplegia. A female patient, aged 48
      years, presented L-dopa-responsive parkinsonism, and her sister had stroke when
      she was 55 years old. MRI was abnormal in all the patients and showed lacunar
      infarctions in the periventricular white matter, basal ganglia and pons. Lesions
      were detected by MRI even before stroke in a female patients. In patients with
      Anderson-Fabry disease, stroke is a frequent complication, and may be the first
      threatening clinical manifestation. In young people with undefined stroke, even
      without signs of renal involvement, it is important to consider the diagnosis of
      Anderson-Fabry disease and so to perform clinical examination and biochemical
      analyses. The pre-clinical stage of cerebrovascular involvement may be evaluable
      by MRI.

PMID- 12235492
TI  - Electrodermal activities and autonomic nervous system in Behcet's patients.
AB  - Behcet's disease is often a progressive disorder. In some cases, there is a
      possibility of subclinical involvement without neurologic signs and symptoms. The
      autonomic nervous system is affected in Behct's disease. The aim of the present
      study was to investigate autonomic nervous system functions in Behct's patients
      by analyzing electrodermal activities. A total of 16 patients and 16 healthy
      volunteers were accepted for the study. Skin potential recordings were taken at
      room temperature in a quiet place within a Faraday's cage. The mean values of
      basal skin potentials and skin potential responses in the patients' group were
      reduced when compared with those of the control group ( p=0.0001). There was no
      difference between the groups regarding the mean values of latency ( p=0.09). The
      findings suggest that electrodermal activities may reflect autonomic nervous
      system dysfunction in Behcet's patients, and the measurement of electrodermal
      activities may be useful for the assessment of autonomic nervous system
      involvement in Behcet's disease.

PMID- 12235493
TI  - Myasthenia gravis outcome measure: development and validation of a disease
      specific self-administered questionnaire.
AB  - We describe the development and validation of an outcome measure for patients
      with myasthenia gravis (MG) and show the correlation of the items with
      conventional MG measurements. In stage I, item generation, a group of
      methodologists, clinical experts generated a list of 56 items. The list was based
      on (1) a previous study on an MG sample, (2) clinical experience and (3) items
      proposed by MG patients. In stage 2, reduction of items, the list was reduced on
      the basis of results from field testing (41 patients completed the 56-item
      questionnaire). In stage 3, reliability and validity were assessed. A 25-item MG
      questionnaire (MGQ) was generated. Results were related to conventional measures
      of MG severity. Furthermore, the MGQ appeared reliable, sensitive and
      reproducible. The questionnaire was validated as an outcome measure.

PMID- 12235494
TI  - Ganglioside a/b ratio in different rat brain regions following chronic diazepam
      treatment.
AB  - Gangliosides are sialic acid-containing glycosphingolipids that play a variety of
      important functions in neurons. The main purpose of this study was to determine
      the a/b ratio of gangliosides in different rat brain regions (cerebral cortex,
      hypothalamus, caudate nucleus, hippocampus, thalamus and cerebellum) after
      prolonged diazepam treatment. Male Wistar rats were maintained on a nutritionally
      adequate diet and diazepam was administered in a dose of 10 mg/kg day for 180
      days. Total gangliosides were extracted according to Harth and the total
      ganglioside-NeuAc content was determined by Svennerholm's resorcinol method,
      modified by Miettinen and Takki-Luukkainen. The a/b ratio remained unchanged in
      rat hypothalamus, thalamus and cerebellum. It was slightly decreased in the
      caudate nucleus and hippocampus, but this was not statistically significant. A
      drastic decrease ( p<0.01) in ganglioside content, compared to control animals,
      was found in rat cerebral cortex. Ganglioside a/b profile did not change
      significantly in most of the brain regions (except in cerebral cortex), which
      suggests that adaptive changes occurred upon prolonged exposure to diazepam, in
      order to maintain the physiological ratio of ganglioside a- and b-series in
      distinct brain areas.

PMID- 12235495
TI  - Complete migration of ventriculoperitoneal shunt into the ventricle.
AB  - Proximal migration of ventriculoperitoneal (VP) shunt is extremely rare. A medium
      pressure VP shunt was inserted in a 10-month-old infant suffering from severe
      hydrocephalus. One month later, complete migration of the shunt into the lateral
      ventricle was encountered. Possible causative mechanisms and the literature on
      this subject are briefly discussed.

PMID- 12235496
TI  - Aphasia as a rare presentation of monosymptomatic demyelinating disease: case
      report and review of the literature.
AB  - We present a case of sudden-onset aphasia due to a single pathological lesion,
      which at neuroradiological imaging studies was suggestive of glioma, while on
      biopsy proved be of demyelinating nature. Every cause of demyelinating lesions of
      the central nervous system was considered in the differential diagnosis,
      concluding for a primary demyelinating disease. The clinical and radiological
      differences between multiple sclerosis and acute disseminated encephalomyelitis
      are discussed. Although aphasia has already been described in demyelinating
      diseases, we underline its rarity as onset symptom.

PMID- 12235497
TI  - [Epidemiology of orofacial pain].
AB  - BACKGROUND: Results of international epidemiologic studies indicate that
      orofacial pain occurs in approximately 10 percent of the adult population. Women
      are constantly more often affected than men by a ratio of 2:1, on the average.
      Most studies show a decline of prevalence in older age. Several sources of
      epidemiologic data about pain in the general population are available in Germany.
      The German National Health Survey ( n=7,124), besides some smaller studies in
      specific German regions, provides detailed results about gender- and age-specific
      prevalence (12 months, 7 days) of orofacial pain. PREVALENCES: With generally
      somewhat higher prevalence figures, results from the National Health Survey are
      well in the range of findings of international studies. Prevalence of orofacial
      pain in the total sample was 16 percent (12 months) and 7 percent (7 days),
      respectively. With 12 months and 7 days prevalence rates of 20 percent and 9
      percent, respectively, women were more frequently affected than men (12 percent,
      5 percent). Data from the National Health Survey also demonstrate that occurrence
      of orofacial pain is often associated with pain in other body regions. Of those
      with orofacial pain during the past 7 days, less than 10 percent reported
      orofacial pain as the sole pain problem. 43 percent of those with orofacial pain
      reported pain in 5 or more other localizations. Orofacial pain was less often
      reported to be the most severe pain problem than pain in other body regions. Yet,
      comparisons of pain intensity reported by subjects who felt that orofacial pain
      was the most severe pain problem during the past 7 days with reports of those who
      indicated that headache, neck pain, or back pain was their most severe pain show
      a similar distribution of mild, moderate and severe pain in these four
      localizations. HEALTH-RELATED QUALITY OF LIFE: Health-related quality of life as
      measured in the National Health Survey by the SF-36 Short Form questionnaire is
      strongly affected by orofacial pain. Even controlling for gender, age, and number
      of pains during the past 7 days statistically significant reduction of scores in
      5 out of 6 SF-36 subscales was observed in those with prevalent orofacial pain.

PMID- 12235498
TI  - [Jaw muscle pain--its neurobiological basis].
AB  - The masticatory muscles show morphologic, histochemical, electrophysical, and
      functional features that differ from the other muscles of the body. At least two
      kinds of masticatory muscle pain should be distinguished: A local pain associated
      with peripheral mechanical overuse, and a pain associated with changes in the
      central nociceptive system. Biomechanical factors appear to be important for the
      first type of muscle pain. Since the typical reaction of a painful muscle
      consists of inhibition of its activity, traditional concepts that postulate the
      maintenance of the pain by chronic overuse of the whole muscle are not supported
      by the current literature. Instead, differential overuse of discrete
      intramuscular regions appear to provide a more plausible explanation. On the
      other hand, the possible relationships between functional and structural
      neuroplastic changes and the second form of chronic muscle pain (e.g.,
      fibromyalgia) still remain speculative.

PMID- 12235499
TI  - [Diagnostic imaging assessment of temporomandibular joint pain].
AB  - INTRODUCTION: In the diagnostic process imaging is frequently performed for
      confirmation of pain symptoms or imaging-based signs were used for conclusions on
      pain. Therefore, the aim of this review was to show evidence about the
      association between temporomandibular joint (TMJ) pain - as a subgroup of
      orofacial pain conditions - and findings on TMJ images. METHODS: By handsearch
      and computer-based search statements of clinical studies, especially of the past
      20 years, were collected and critically assessed. RESULTS AND CONCLUSIONS: In the
      literature there exist some references to and indications for an association
      between TMJ pain and structure-based findings on TMJ images, i.e. morphology of
      the condyle, condyle-fossa relationship, form and position of the disc, signs of
      effusion of the upper resp. lower joint compartment, bone marrow signal
      abnormalities of the condyle, signal characteristics of the retrodiscal tissue.
      Despite some hints the relation between TMJ pain and so-called abnormalities on
      TMJ images remains unclear, complex and little predictive in individual cases.

PMID- 12235500
TI  - [Psychosocial factors in patients with temporomandibular pain].
AB  - The significance of psychosocial factors (pain concepts, psychological distress
      eg. depression and anxiety, disability) in patients with temporomandibular pain
      is increasingly noticed. The major diagnostic domains as well as the appropriate
      diagnostic procedures are described. Management should be based on a model
      elaborated in cooperation with patients, as to the formation and maintenance of
      the pain condition. It should be individualized as much as possible. For the
      majority of patients, symptomatic treatment in combination with clear behavioral
      directions is sufficient. However, some studies show that improvement is more
      stable and faster in patients with combined treatment conditions (e.g.occlusal
      appliance, stress management, relaxation training) than in patients receiving
      only singular treatment.

PMID- 12235501
TI  - [Principles on therapy of myoarthropathic pain].
AB  - The myoarthropathic pain is the major source of orofacial pain. The diagnosis is
      not always easy because the diagnostic signs are not pathognomonic and they may
      occur also with other pain disorders. The pain intensity fluctuates, and mild to
      medium intensity pain has the tendency to subside spontaneously or can be
      alleviated with simple, non-invasive therapies as counseling, self-control,
      analgesics, physiotherapy, and occlusal appliances. For most patients a
      combination of counseling, self-control and physiotherapy (home program) is
      sufficient to relieve the pain. Occlusal appliances should therefore be used only
      if these modalities fail or in presence of pain on awakening, ostheoarthritis, a
      painful discopathy, and/or a malocclusion caused by condylar remodeling secondary
      to ostheoarthrosis. Only in a small percentage of patients the myoarthropathic
      pain persists and becomes chronic. These patients need a multimodal therapy,
      according to the biopsychosocial pain model. In addition to the modalities just
      described, the treatment must address also the affective, emotional, cognitive,
      and behavioral pain component and be tailored to the single patient based on
      his/her psychosocial and constitutional characteristics. The goal is not pain
      relieve but improvement of the quality of life by teaching the patient more
      efficient pain coping strategies by means of behavioral and relaxation therapy.
      In addition, tricyclic antidepressants may be used in order to treat the somatic
      pain component caused by the neuroplastic changes that take place in the central
      nervous system in chronic pain conditions.

PMID- 12235502
TI  - [Pharmacotherapy of orofacial pain].
AB  - OBJECTIVES: Pharmacotherapy of chronic orofacial pain is unsatisfactory. Here we
      set out to prepare a systematic review of randomized controlled clinical trials
      (RCTs) on pharmacotherapy of facial pain. METHODS: The diagnostic groups
      "temporomandibular disorders" (TMDs), "atypical facial pain", and "trigeminal
      neuralgia" were included. RCTs published between 1966 and August 2001 were
      identified by Medline search, from review articles, and from the Cochrane and
      Bandolier databases. The quality of the trials was judged according to
      established criteria. Good or excellent pain reduction or >50% pain reduction
      were used as endpoints for successful treatment. Numbers needed to treat (NNTs)
      and their 95% confidence intervals were calculated where dichotomous data were
      available. RESULTS: Twelve studies were identified for the TMDs, 11 for
      trigeminal neuralgia, four for atypical facial pain. Many studies had
      methodological problems and small numbers of patients. There was sufficient
      evidence of efficacy of carbamazepin in trigeminal neuralgia, also for baclofen
      and lamotrigine. In the TMD studies, there was evidence of a moderate effect of
      muscle relaxants/tranquilizers. Two studies of atypical facial pain showed a
      moderate effect of antidepressants. CONCLUSIONS: Apart from studies in trigeminal
      neuralgia, there is little evidence of efficacy of pharmacotherapy in orofacial
      pain. High quality studies with sufficient numbers of patients using operational
      definitions of disease entities are warranted.

PMID- 12235503
TI  - [Burning mouth].
AB  - BACKGROUND: The complaint of burning mouth is fairly common. Epidemiological
      studies suggest a prevalence of around 15% in postmenopausal women and between
      0,7 and 7,9% for the general population. PURPOSE: The purpose of this article is
      to present a review of the literature on epidemiology, clinical symptoms,
      etiology, diagnosis, treatment and prognosis of burning mouth and burning mouth
      syndrome. RESULTS AND CONCLUSIONS: Potential causal factors have been extensively
      studied and reviewed, suggesting a multifactorial aetiology, that apparently
      includes local, systemic and psychogenic factors. However, reports of their
      relative importance are conflicting. Consequently this lack of evidence is
      reflected in inconsistent guidelines for diagnosis and treatment. Most of the
      authors emphasize the importance of history taking and clinical intraoral
      examination for diagnosis. The symptom of burning mouth associated with clinical
      mucosal abnormality has to be differentiated from burning mouth syndrome (BMS), a
      condition in which no mucosal abnormality is evident on examination. Whereas the
      symptom of burning mouth associated with clinical mucosal signs is described to
      be often manageable by eliminating possible causal factors, the background of
      most of the proposed treatments for BMS is empiric or even purely anecdotal. Only
      a few randomised controlled studies have been performed on treatment outcome.
      Their differing results are presented in a short overview.

PMID- 12235504
TI  - [Chronic facial pain from psychiatric point of view - differential diagnosis and
      therapeutic strategies].
AB  - Chronic facial pain may cause diagnostic and therapeutic difficulties, thus
      demanding a complete interdisciplinary consultation. As in 20 to 25% of patients
      with a nociceptive or primary neuropathic pain a psychiatric comorbidity is
      expected, it is necessary to include psychiatric and psychosomatic examinations.
      Every 8th male and every 4th female pain patient has the statistical risk of
      having a depression at the same time. Depression may develop as a consequence of
      pain, but may also be the primary basis for a pain syndrome. An independent
      coincidence is possible as well. Besides affective disorders, persistent
      somatoform pain syndromes, syndromes of conversion, hypochondriac or artificial
      disorders and pain in psychosis have to be excluded in patients presenting with
      chronic facial pain. In depression, persistent somatoform pain syndromes,
      atypical facial pain but also when dysfunctional illness beliefs and coping
      mechanisms are present, cognitive-behavioral therapy should be offered to the
      patient. Motivation to psychotherapy may be difficult, especially in patients
      relying exclusively on physical illness beliefs. The physician should develop and
      extend the physical illness beliefs together with the patient to a model that
      includes biological as well as psychosocial factors. Tricyclic antidepressants
      may be indicated not only in depression, but also in chronic pain due to the
      analgetic effects of these drugs. The choice of drug therapy should conform to
      the main complaints of depression and accompanying illnesses. Indication of
      antidepressants or neuroleptic drugs in somatoform pain syndromes is still
      unclear. Their potential slight effect may simply be due to the high comorbidity
      between somatoform pain syndromes and depression.

PMID- 12235505
TI  - [Neurosurgical therapy of facial neuralgias].
AB  - INTRODUCTION: Neuralgias of the face, especially trigeminal neuralgia and
      glossopharyngeal neuralgia are indications for surgical interventions after
      failed medical therapy. In contrast to other forms of headache or atypical facial
      pain, where surgical measures are considered to be contraindicated, percutaneous
      procedures or microvascular decompression are able to produce immediate and
      longstanding pain relief. Careful preoperative evaluation is essential to confirm
      the clinical diagnosis and to rule out other causes as multiple sclerosis or
      tumors afflicting the cranial nerves. The following study will summarize the
      common surgical techniques and their role considering a mechanism-based therapy
      as well as document long-term results of these measures. METHODS: Between 1977
      and 1997 316 thermo-controlled radiofrequency trigeminal rhizotomies (TK) and 379
      microvascular decompressions (MVD) were performed in our hospital to treat
      trigeminal neuralgia; additional 6 MVDs for glossopharyngeal neuralgia and one
      MVD of the intermediate facial nerve were carried out. Questionnaires were sent
      out to all patients still living in 1981, 1982, 1992 and 1998. For all other
      patients, interviews with relatives or the general practitioners were conducted.
      A retrospective analysis of postoperative pain relief was performed using Kaplan
      Meier curves at the latest follow-up. Additionally 80 patients underwent careful
      quantitative sensory testing with Von-Frey-hairs. RESULTS: 225 patients who
      underwent microvascular decompression and 206 with radiofrequency trigeminal
      rhizotomies were further analyzed. There was a 50% risk for pain recurrence two
      years after radiofrequency rhizotomy. On the other hand 64% of patients who
      underwent microvascular decompression remained painfree 20 years postoperatively.
      Patients with microvascular decompression without sensory deficit were painfree
      significantly longer than patients with postoperative hypesthesia. DISCUSSION:
      Etiology and pathogenesis of facial neuralgias are far from understood despite
      several hypotheses. Based on current models there is no explanation for the
      immediate pain relief especially after microvascular decompression. Some authors
      even discuss surgical trauma as the only cause for postoperative pain relief.

PMID- 12235506
TI  - Results of a randomized trial of HERMES-assisted versus non-HERMES-assisted
      laparoscopic antireflux surgery.
AB  - BACKGROUND: Speech recognition technology is a recent development in minimally
      invasive surgery. This study was designed to assess the impact of HERMES on
      operating room efficiency and user satisfaction. METHODS: Patients undergoing
      laparoscopic antireflux operations by surgeons experienced in minimally invasive
      surgery were randomized to HERMES-assisted or standard laparoscopic operations.
      The variables of interest were circulating nurse's time spent adjusting devices
      that are voice-controlled by HERMES, number of adjustments to devices requested,
      and surgeon and nurse satisfaction measured on a scale from 1 (dissatisfied) to
      10 (satisfied). RESULTS: A total of 30 cases were studied. In the non-HERMES
      cases, nurses were interrupted to make device adjustments an average of 15.3
      times per case versus 0.33 times per case in the with-HERMES cases (p < 0.01).
      The interruptions during the non-HERMES cases averaged 4.35 min per case versus
      0.16 min per case in the with-HERMES cases (p = 0.03). Average satisfaction
      scores for HERMES operations as opposed to non-HERMES operations were 9.2 versus
      5.3 for nurses (p < 0.01) and 9.0 versus 5.1 for surgeons (p < 0.01).
      CONCLUSIONS: Physician and nurse acceptance of HERMES was very high because of
      the smoother interruption-free environment.

PMID- 12235507
TI  - Controlled trial of the introduction of a robotic camera assistant (EndoAssist)
      for laparoscopic cholecystectomy.
AB  - BACKGROUND: The role of the human camera holder during laparoscopic surgery keeps
      valuable personnel from other duties. EndoAssist is a robotic camera-holding
      device controlled by the operator's head movements. This study assesses its
      introduction into clinical practice. METHOD: Ninety-three patients undergoing
      laparoscopic cholecystectomy were randomized to have either the robotic (40) or a
      human (46) assistant. Seven patients converted to open operation were excluded.
      Six surgeons were evaluated. Operating time and subjective assessments were
      recorded. Learning curves were constructed. RESULTS: The mean operating time was
      less using the robotic assistant (66 min) than with human assistance (74 min) (p
      < 0.05, two-tailed t-test). The learning curves for operating time showed that
      within three operations surgeons were trained in using the robot. The device was
      safe in use. CONCLUSION: The EndoAssist operating device is a significant asset
      in laparoscopic surgery and a suitable substitute for a human assistant. Surgeons
      became competent in the use of the robot within three operations. The robot
      offers stability and good control of the television image in laparoscopic
      surgery.

PMID- 12235508
TI  - Comparison of laparoscopic choledochotomy closure techniques.
AB  - BACKGROUND: Laparoscopic common bile duct exploration (CBDE) has traditionally
      been accompanied by T-tube drainage. However, other methods of choledochotomy
      closures have been reported. This study compared three laparoscopic methods of
      choledochotomy closure in a prospective, randomized fashion to determine which
      method should be the preferred technique. METHODS: In this porcine model, 24
      animals initially underwent laparoscopic common bile duct (CBD) clipping to
      simulate an obstruction. Two days later, the animals underwent laparoscopic clip
      removal and simulated CBDE through a 1.5-cm choledochotomy. The animals were then
      randomized to one of three groups: primary choledochotomy closure (group I),
      antegrade CBD stenting with primary closure (group II), or T-tube placement
      (group III). To assess for CBD stenoses and leaks, the animals were killed 2
      months postoperatively, at which time a cholangiogram was performed and the bile
      duct harvested. The ratio of proximal CBD to choledochotomy site was assessed
      radiographically and histologically. RESULTS: The operative time was
      significantly longer in group III (200 +/- 13 min, p < 0.05) than in group I (141
      +/- 17 min) and group II (154 +/- 16 min). The ratio of the proximal CBD diameter
      to the choledochotomy site diameter by cholangiogram was 2.1:1.0 in group I, to
      1.2:1.0 in group II, and 1.1:1.0 in group III (p < 0.01). The ratio of the
      proximal CBD intraluminal area to the choledochotomy site intraluminal area was
      2.1:1.0 in group I compared to 1.1:1.0 in groups II and III (p < 0.01). None of
      the animals developed jaundice or sepsis. CONCLUSION: Significant stenoses were
      present at the choledochotomy site in the primary closure group, and T-tube
      placement resulted in prolonged operative times. We conclude that laparoscopic
      antegrade CBD stenting with primary closure of the choledochotomy site is the
      preferred technique after choledochotomy in an animal model. Further assessment
      in a clinical trial is warranted.

PMID- 12235509
TI  - Laparoscopy-assisted hepatectomy using the Endoclose: a case report.
AB  - Hemostasis of a resected stump of liver is extremely difficult in laparoscopic
      hepatectomy. Although Pringle's maneuver, which is a total clamping of the
      hepatoduodenal ligament, is a useful technique, it is often difficult in
      laparoscopic circumstances. Moreover, total inflow occlusion leads to
      postoperative liver damage. Therefore, the local bleeding method is ideal. The
      Endoclose, a device for port site closure, is formed from an outer sheath and an
      inner needle with a notch to load the suture. The Endoclose is loaded with a
      suture and passed through the liver. The suture is left under the liver, and the
      device is removed. Next, the suture carrier is passed through the liver at an
      appropriate distance, and the suture is regrasped by this suture carrier and
      brought out of the liver. Herein we report a case in which a new bleeding control
      method using Endoclose was introduced for laparoscopy-assisted hepatectomy.

PMID- 12235510
TI  - Hand-assisted laparoscopic hepatic resection.
AB  - Thanks to recent advances, performance of liver resection is now possible using
      laparoscopic procedures. However, still there are some difficulties to overcome.
      The hand-assisted method lends safety and reliability to the laparoscopic
      procedure. A 54-year-old man diagnosed with hepatocellular carcinoma (HCC) was
      referred for hepatectomy. Angiography with computed tomography (CT) scans
      revealed a 2-cm hepatocellular carcinoma (HCC) at segment V, close to the
      gallbladder. A hand-assisted laparoscopic hepatic resection was performed. Four
      10-mm trocars, one for wall lifting and three for working, were placed in the
      upper abdomen. A small incision was added at the right side of umbilicus, and the
      operator's left hand was inserted through it. A microwave tissue coagulator and
      laparoscopic ultrasonic dissector were used for liver resection. Total operation
      time was 162 min; blood loss was 20 g. The postoperative course was uneventful,
      and the postoperative hospital stay was 7 days. We thus demonstrated that
      laparoscopic liver resection is safer and easier when the hand of the operator
      can be inserted into the abdomen. The small incision does not greatly diminish
      the benefits that accrue from minimally invasive laparoscopic surgery. The hand
      assisted procedure allows better access to the tumor. In addition, hand
      assistance restores the sense of touch to the operator and is an effective means
      of controlling sudden and unexpected bleeding.

PMID- 12235511
TI  - Videofluoroscopy of the swallowing act after partial supraglottic laryngectomy by
      CO(2) laser.
AB  - The evaluation of functional deglutition in patients after partial supraglottic
      laryngectomy by CO(2) laser was performed by videofluoroscopy of the swallowing
      act. We studied 20 patients in PA and LL projections, and the swallowing act, at
      25 frames per s, was captured on videotape. Aspiration was found in six patients,
      four of whom had manifest clinical symptoms of aspiration. Four patients had post
      deglutitive, one intra-deglutitive and one both intra- and post-deglutitive
      aspiration. Other swallowing disturbances or structural deformities were not
      detected. Dynamic radiological studies of swallowing, such as videofluoroscopy of
      the swallowing act, can provide valuable information regarding functional results
      after surgical procedures in the upper aerodigestive tract. Our encouraging
      results prove the validity of partial supraglottic laryngectomy by CO(2) laser as
      a method of treatment for carcinoma of the larynx.

PMID- 12235512
TI  - Management of tracheal stenosis with a titanium ring and nasal septal cartilage.
AB  - Surgical management of subglottic laryngeal and upper tracheal stenosis remains a
      formidable challenge. The significant number of proposed techniques only
      highlights the difficulties associated with effectively managing this problem.
      Between 1996 and 1999, seven patients with stenosis of the upper trachea were
      treated. The stenosis resulted from long-term intubation during intensive-care
      hospitalization in five patients and from tracheotomy complications in the other
      two. Six patients were male and one female, their ages ranging between 13 and 60
      years. The mean postoperative observation period was 3 years (1.5-4.5 years). In
      all patients, the stenosis exclusively involved the upper tracheal segment,
      measuring from 2 to 5 cm in length. The stenotic area of the trachea is exposed,
      and the local application of a solution of mitomicin C for a duration of 4 min is
      performed. A graft consisting of cartilage and mucosa is harvested from the nasal
      septum and is fixed with sutures to a titanium semi-ring. After the fixation of
      the graft on the ring, the entire construct is placed on the stenosed segment of
      the exposed trachea. The graft must cover the anterior exposed face of the
      trachea with the lateral members of the semicircular titanium ring adjacent to
      the lateral walls of the trachea, externally. The lateral tracheal walls are
      attracted laterally with sutures and are attached on the edges of the
      semicircular titanium ring. Four of the patients in whom no tracheotomy had been
      performed preoperatively needed none at all intraoperatively, and they were
      decannulated normally at the end of the procedure. Tracheotomy was deemed
      necessary for one patient's safety and was maintained for 7 days. In one patient
      with a preoperative tracheotomy, the point of the tracheotomy was displaced lower
      on the trachea and was maintained there for 7 days. The course of management
      described here and employed on seven patients involves a safe surgical procedure
      with excellent results. The placement of the titanium ring offers very good
      support for the graft and maintains the patency of the tracheal lumen. The main
      reasons for the failure of techniques using only cartilage grafts are therefore
      avoided. The number of cases presented here is certainly too small to establish
      definite conclusions; however, the initial results are extremely satisfying and
      urge us to suggest the use of this method in indicated cases.

PMID- 12235513
TI  - Internal jugular vein patency after lateral neck dissection: a prospective study.
AB  - In spite of anatomical preservation of the internal jugular vein (IJV), an
      occlusion rate of the vessel of up to 30% has been documented after selective or
      modified radical neck dissections. The aim of the present prospective study was
      to evaluate the patency of the IJV following selective lateral neck dissection
      (LND) in 34 patients affected by squamous cell carcinoma of the upper
      aerodigestive tract who underwent surgery concomitantly on the primary site and
      the neck. Eighteen patients received unilateral and 16 bilateral LND, for a total
      of 50 IJVs. Postoperative radiotherapy on the neck was delivered in four patients
      with histologic evidence of micro-extracapsular spread; the impact of this
      variable on IJV patency was assessed by the Fisher test. A preoperative baseline
      study of vein patency and flow by ultrasonography (US) was obtained.
      Postoperative controls were scheduled at 1 week, 1 month and 3 months following
      surgery. No patient developed either wound infection or a pharyngocutaneous
      fistula, and no signs or symptoms of IJV occlusion were observed during the
      postoperative course. At the first US control, 25 IJVs (50%) did not present any
      alteration in patency, and 23 (46%) and 2 (4%) had a reduced or absent flow,
      respectively. At the second and third controls, 33 (66%) and 45 (90%) of the IJVs
      presented with normal flow, respectively. At the end of the study, none of the
      patients showed evidence of occlusion. Postoperative radiotherapy did not have a
      statistically significant impact on IJV patency ( P=0.09). In conclusion, long
      term IJV occlusion after LND has to be considered an exceedingly rare event with
      negligible morbidity. However, alterations of IJV flow frequently occur in the
      immediate postoperative course.

PMID- 12235514
TI  - Immunolocalization of inducible nitric oxide synthase and 3-nitrotyrosine in
      recurrently inflamed, human palatine tonsils.
AB  - The purpose of this study was to evaluate the possible involvement of nitric
      oxide and its toxic metabolite--peroxynitrite--in the pathogenesis of recurrent
      tonsillitis. Tonsil specimens with recurrent inflammation were obtained from
      patients who required tonsillectomies as surgical treatment for their conditions.
      The relatively normal tonsils were obtained from patients who underwent uvulo
      palato-pharyngoplasty for habitual snoring or obstructive sleep apnea. The sites
      of inducible nitric oxide synthase (iNOS) expression in the tonsil specimens were
      examined with an immunohistochemical technique. The possible production of
      peroxynitrite was evaluated by immunolabeling of 3-nitrotyrosine (3-NT) as its
      biological footprint. Each section was given a score of 0 to 4 according to the
      labeling intensity seen, with the highest number representing the highest
      labeling intensity. We found that tonsils with recurrent inflammation had iNOS
      expression mainly in the mucosal epithelium, subepithelial regions and vascular
      endothelium. The parenchyma of the tonsils, where T- and B-cell clones are
      located, showed little iNOS immunoreactivity. The accumulation of 3-NT had a
      similar distribution pattern to that of iNOS expression. However, the normal
      tonsils showed limited iNOS expression on mucosal epithelium and rare 3-NT
      accumulation. Recurrently inflamed tonsils had significantly higher labeling
      scores for both iNOS and 3-NT compared to normal tonsils. Further, a higher iNOS
      score correlated with a higher 3-NT accumulation. These data suggest that iNOS
      expression and the formation of peroxynitrite may have an important role in the
      pathogenesis of recurrent tonsillitis.

PMID- 12235515
TI  - Angioneurotic edemas of the upper aerodigestive tract after ACE-inhibitor
      treatment.
AB  - There are rare cases in which inhibitors of the angiotensin-converting enzyme can
      cause an angioneurotic edema of the upper aerodigestive tract. The pathomechanism
      of this side effect depends on an interaction of the drug with hormones
      regulating vascular permeability, such as the kallikrein kinin system and the
      prostaglandin system. Angioedema is characterized by subcutaneous or submucosal
      swellings, which usually affect the lips, soft palate, tongue and larynx.
      Pathomechanisms, differential diagnosis and treatment of ACE-inhibitor-induced
      edema of the upper aerodigestive tract are described in three case reports.

PMID- 12235516
TI  - Rapid hematopoietic engraftment following fractionated TBI conditioning and
      transplantation with CD34(+) enriched hematopoietic progenitor cells from
      partially mismatched related donors.
AB  - Nineteen adult patients with poor-risk hematologic malignancy received T cell
      depleted (TCD) hematopoietic progenitor cell (HPC) transplant from partially
      mismatched related donors (PMRD). The preparative regimen (FITFA) included
      fractionated TBI, thiotepa, fludarabine, and horse (n = 3) or rabbit (n = 16)
      anti-thymocyte anti-sera (ATG). GVHD prophylaxis consisted of TCD by
      positive/negative selection using the Isolex 300i system and pre-transplant ATG
      with no post-transplant immunosuppression. The mean number (+/-s.d.) of
      transplanted CD34(+) and CD3(+) cells were 8.9 x 10(6)/kg +/-4.3 (range 2.6-19.3)
      and 1.4 x 10(4)/kg +/-1.2 (range 0.3-4.6) respectively. Seventeen patients
      evaluable for neutrophil engraftment achieved an ANC >0.5 x 10(9)/l at a median
      of 12 days (range 9-27), with evidence of full donor chimerism. Thirteen patients
      died of the following causes: relapse (n = 6), infections (n = 5), interstitial
      pneumonia (n = 1), and unknown causes (n = 1) None of the recipients of rabbit
      ATG required therapy for acute or chronic GVHD. Five patients are alive and
      disease-free at a median time of 303 days post transplant (range 100-660). The
      FITFA preparative regimen using fractionated TBI is well tolerated and is
      sufficiently immunosuppressive to allow rapid and stable donor origin
      hematopoietic engraftment without 'mega' doses of CD34(+) cells. Combination of
      stringent ex vivo TCD and pre-transplant ATG is effective GVHD prophylaxis.

PMID- 12235517
TI  - The helper T lymphocyte precursor (HTLp) frequency does not predict outcome after
      HLA-identical sibling donor G-CSF-mobilised peripheral blood stem cell
      transplantation.
AB  - Here, we report the first study assessing the helper T lymphocyte precursor
      (HTLp) frequency as a predictor of outcome in patients undergoing allogeneic PBSC
      transplantation. The HTLp assay uses limiting dilution analysis to measure the
      frequency, in PBMCs from the donor, of T lymphocytes capable of producing IL-2 in
      response to histocompatibility antigenic differences on PBMCs from the recipient.
      This assay has shown promise as a functional histocompatibility assessment used
      to predict the risk of recipients of HLA-matched donor bone marrow developing
      severe acute GVHD: the higher the HTLp frequency, the greater the significance of
      any histoincompatibility, and the greater the risk of severe acute GVHD. In the
      current report, the HTLp frequency was measured in 28 HLA-identical sibling pairs
      who subsequently underwent allogeneic PBSC transplantation for haematological
      malignancies. The HTLp frequency did not predict for acute GVHD (P = 0.38),
      chronic GVHD (P = 0.95), transplant-related mortality (P = 0.79), relapse (P =
      0.39) or overall survival (P = 0.84). Converting the HTLp frequency to HTLp
      infused per kilogram of recipient body weight also did not predict for any of the
      outcome measures. We conclude that, although the HTLp assay may be useful for
      patients undergoing BMT, it does not predict for outcome after HLA-identical
      sibling donor G-CSF-mobilised PBSC transplantation.

PMID- 12235518
TI  - The impact of antithymocyte globulin on short-term toxicity after allogeneic stem
      cell transplantation.
AB  - Antithymocyte globulin (ATG) is commonly used in allogeneic haematopoietic stem
      cell transplantation (HSCT). Little information is available, however, as to the
      optimal protocol for use and the side-effects occurring if ATG is administered in
      high daily doses (10-30 mg/kg). We report our experience with ATG Fresenius (ATG
      F) in conditioning for allogeneic HSCT. During a period of 3 days, 47 patients
      received doses between 10 and 30 mg/kg either over 4 h preceded by 1-1.5 mg/kg
      prednisolone 30 min before the start of ATG-F (protocol A) or alternatively, over
      12 h with 3-4 mg/kg prednisolone being administered before and 6 h after start of
      ATG (protocol B). During treatment with ATG-F, the side-effects observed included
      inflammation, disseminated intravascular coagulation, hyperdynamic circulation
      and renal dysfunction. Although these complications caused substantial morbidity,
      they were reversible within a few days. Side-effects were significantly more
      severe in patients treated according to protocol A than in those treated
      according to protocol B. As prolonged infusion of ATG-F does not reduce T cell
      clearance due to the long half-life of ATG-F, and since less cytokine release
      during conditioning might have beneficial long-term effects, we recommend
      administering ATG-F over 12 h preceded by high-dose steroid treatment.

PMID- 12235519
TI  - Engraftment syndrome in children undergoing autologous peripheral blood
      progenitor cell transplantation.
AB  - There is limited experience on engraftment syndrome (ES) in children. The present
      study analyzes the characteristics of ES in pediatric patients undergoing
      autologous peripheral blood progenitor cells transplantation (PBPCT). From 1993
      to 2001, 30 of 156 patients (19.2%) who underwent PBPCT developed ES (skin rash
      which involved more than 27% of the body surface and temperature >38.3 degrees C
      with no compatible infectious disease etiology, during neutrophil recovery). Of
      the 30 patients who developed ES, 20 (66%) developed hypoxia and/or pulmonary
      infiltrates, seven (23%) had hepatic dysfunction, six (20%) developed renal
      insufficiency, 16 (53%) showed weight gain and three (10%) experienced transient
      encephalopathy. Multivariate analysis showed that the only positive predictive
      factor for developing ES was mobilization with high-dose G-CSF (12 microg/kg
      twice daily) (RR 3.88, CI 95% 1.73-8.67; P < 0.0005). The overall transplant
      related mortality (TRM) was 8.33% and this was significantly higher in the
      patients who developed ES than in those who did not (23% vs 4.76%; P < 0.0001).
      We also found a higher morbidity in patients who developed ES, expressed as a
      statistically significant increase in supportive care (transfusion requirement,
      parenteral nutrition) and increase in the length of hospital stay. In summary, we
      have found ES to be the most important cause of morbidity and mortality in
      children undergoing autologous PBPCT.

PMID- 12235521
TI  - Fludarabine/melphalan conditioning for allogeneic transplantation in patients
      with multiple myeloma.
AB  - The purpose of the study was to determine the feasibility and efficacy of a
      reduced intensity conditioning regimen of fludarabine and melphalan for
      allogeneic transplantation in patients with multiple myeloma. From August 1996 to
      December 2000, 22 patients received a reduced intensity conditioning regimen with
      fludarabine and melphalan. Median age was 51 years (range, 45-64), median time
      from initial therapy to transplant was 36 months (range, 3-135 months). Disease
      phase prior to transplant was primary refractory in two patients, refractory
      relapse in 11 patients, sensitive relapse in eight patients and initial remission
      consolidation in one patient. The median number of prior therapies was five
      (range, 1-7), and median beta 2 microglobulin prior to transplant was 3.0 mg/l
      (range, 1.0-7.3). All patients received unmanipulated grafts from either HLA
      matched sibling donors (n = 13) or matched unrelated donors (n = 9). Eighteen
      patients received fludarabine 30 mg/m(2) for 4 days with melphalan 140 mg/m(2) as
      a single dose and four patients received fludarabine 25 mg/m(2) for 5 days with
      melphalan 90 mg/m(2) daily for 2 days. All 21 patients evaluable for engraftment
      achieved a neutrophil count of >0.5 x 10(9)/l after a median of 12 days (range, 9
      24), 18 patients achieved platelet transfusion independence after a median of 14
      days (range, 8-47). All engrafting patients had 100% donor cell engraftment.
      Seven patients achieved a complete remission. Six patients are currently alive
      with a median follow-up of 15 months (range, 10-47 months). The actuarial
      survival and progression-free survival is 30 +/- 11% and 19 +/- 9% at 2 years.
      Non-relapse mortality at 100 days was 19 +/- 10% and 40 +/- 10% at 1 year.
      Fludarabine/melphalan combinations are feasible and allow consistent engraftment
      of allogeneic progenitor cells from both related and unrelated donors in patients
      with multiple myeloma and should be explored in patients with less advanced
      disease.

PMID- 12235520
TI  - Partially matched related donor peripheral blood progenitor cell transplantation
      in paediatric patients adding fludarabine and anti-lymphocyte gamma-globulin.
AB  - Twenty-one paediatric patients (11 males and 10 females) received a CD34-selected
      partially matched related donor transplant for malignant (16 cases) and non
      malignant conditions (five cases). The average cell dose was 11.13 x 10(6)/kg.
      Fifteen of 16 patients with malignant conditions and one with non-malignant
      disease received total body irradiation plus cyclophosphamide. Three of 5
      patients with non-malignant conditions and one with leukaemia, received busulphan
      plus cyclophosphamide. One patient with Fanconi anaemia received 100 mg/kg of
      cyclophosphamide. Fludarabine (25 mg/m(2)/day for 5 days) was administered prior
      to all these regimens. Additionally, anti-lymphocyte gamma-globulin (12.5
      mg/kg/day) was administered from day -2 to day +2. Three (15%) patients failed to
      achieve complete chimaerism (CC). These patients received a second cell infusion.
      Two of them achieved CC. In the third patient, the percentage of donor cells was
      increased. The likelihood for engraftment was not related to the cell dose
      received. Acute graft-versus-host disease (GVHD) occurred in nine patients but
      only one developed GVHD >grade II. Eight patients developed active viral
      infections, which resolved after treatment. Patients receiving cell doses higher
      than our average had a significantly faster CD3 and CD4 cell recovery and
      experienced a lower incidence of viral infections. After 480 +/- 255 days of
      median follow-up, 16/21 patients are alive and well and have CC. Three patients
      died of leukaemic relapse and a fourth from progression of his disease (adreno
      leuko-dystrophy). We conclude that partially matched related donors are a
      feasible source of haemopoietic progenitor cells for transplantation for patients
      without matched familial or unrelated donors.

PMID- 12235522
TI  - Macrophage migratory inhibitory factor (MIF) expression in acute graft-versus
      host disease (GVHD) in allogeneic hemopoietic stem cell transplant recipients.
AB  - Graft-versus-host disease (GVHD) is a major complication after hemopoietic stem
      cell transplantation (HSCT), but its pathogenesis remains uncertain. Macrophage
      migratory inhibitory factor (MIF) is an important mediator in the allo-immune
      reaction during renal transplantation, yet its role in hemopoietic stem cell
      transplantation (HSCT) remains unexplored. This study investigated the potential
      role of MIF in acute graft-versus-host disease (aGVHD) following allogeneic HSCT.
      Forty-six randomly selected patients undergoing autologous or allogeneic HSCT
      were studied. Immunohistochemistry and in situ hybridization were performed to
      examine tissue MIF mRNA and protein expression on skin and colonic biopsy
      specimens. The associated T cell and macrophage activation was also studied by
      immunohistochemical studies. A semi-quantitative method was used to assess MIF
      staining, as well as T cell and macrophage staining. Serial blood samples were
      analyzed by ELISA for serum MIF levels. Immunohistochemistry and in situ
      hybridization performed in 15 skin and 19 colonic biopsies from 17 patients who
      developed moderate to severe aGVHD showed a significant increase in MIF mRNA and
      protein expression compared with normal controls (seven skin and five colonic
      biopsies). MIF was localized within the epidermis and the vascular area of skin,
      but diffusely expressed in the entire thickness of colon. Macrophage and T
      lymphocyte infiltration was confined to areas of strong MIF expression. Serial
      analysis by ELISA showed that only patients who developed aGVHD (n = 19)
      exhibited an increase (two- to three-fold) in serum MIF during HSCT, but not in
      the allogeneic HSCT recipients without aGVHD (n = 7) or those who received
      autologous HSCT (n = 8). In 14 out of 19 patients, serum MIF peaked before the
      onset of aGVHD. Local and systemic up-regulation of MIF expression is associated
      with the occurrence of acute GVHD. Its pathogenetic role remains to be further
      determined.

PMID- 12235523
TI  - Flow cytometric findings in platelets of patients following allogeneic
      hematopoietic stem cell transplantation.
AB  - Following allogeneic hematopoietic stem cell transplantation (HSCT) patients may
      have an increased bleeding tendency in spite of a normal platelet count.
      Moreover, an association between chronic graft-versus-host disease (cGVHD) and a
      thrombophilic state has been observed. Platelet receptors and granules from 27
      patients following HSCT (13 without cGVHD, 14 with cGVHD) were evaluated by flow
      cytometric analysis and compared to 62 healthy controls. Platelets from HSCT
      patients stained weakly with mepacrine indicating a reduced content of dense
      bodies, whereas no significant degranulation reaction of alpha granules and
      lysosomes was detectable. In addition, a lower surface expression of GP Ia/IIa
      was observed, indicating an acquired thrombocytopathy. The surface receptors are
      activated in HSCT patients, which could be seen by the lower surface expression
      of GP Ib internalized during the activation process and elevated levels of LIBS-1
      and PAC-1 antibody binding. Patients with cGVHD had a seven-fold increased ratio
      of microparticles. This study demonstrates platelet receptor and granule defects
      in patients following HSCT. The key role of platelets in HSCT-associated
      hemostatic disorders is underscored by the high levels of circulating
      microparticles in cGvHD patients which might explain the thrombophilic state in
      these patients.

PMID- 12235524
TI  - Performance of a hybrid central venous catheter utilized for both peripheral
      blood stem cell harvest and transplant support of patients undergoing autologous
      peripheral blood stem cell transplantation.
AB  - Patients undergoing autologous peripheral blood stem cell transplantation (PBSC)
      frequently require the sequential insertion of two central venous catheters, one
      for leukapheresis and one for transplant support. Hybrid catheters suitable for
      leukapheresis and long-term use have been increasingly used, but there is limited
      information regarding their performance and complication rate. The purpose of
      this study was to determine the performance of the Pheres-Flow hybrid catheter
      when utilized for both leukapheresis and transplant support, with particular
      emphasis on the incidence of infectious and occlusive complications. We
      prospectively analyzed the performance of 92 catheters in 82 consecutive patients
      who underwent autologous peripheral blood stem cell (PBSC) transplantation.
      Occlusion was the most frequent complication of this catheter with 29% of the
      patients experiencing difficulty drawing blood or infusing fluids. Infection was
      another frequent complication. Twenty-two percent of patients developed catheter
      related bloodstream infections and 15 catheters had to be removed because of
      proven or suspected infection that did not respond to antibiotic therapy.
      Nevertheless, 77% of patients were able to complete leukapheresis and transplant
      support with only one catheter. We conclude that the utilization of the Pheres
      Flow catheter for both leukapheresis and transplant support is feasible, but that
      new strategies need to be developed to decrease the incidence of occlusive and
      infectious complications of hybrid catheters.

PMID- 12235525
TI  - A case of severe B cell deficiency after allogeneic stem cell transplantation.
AB  - Insufficient immunological reconstitution is one of the serious complications of
      allogeneic stem cell transplantation (SCT). We report a case of severely impaired
      B-lymphopoiesis after allogeneic SCT for CML. The patient's bone marrow and blood
      cells display complete chimerism and he is currently free from leukemia. His
      serum immunoglobulin levels are below detection level, and B cells are absent at
      2 years post transplant in both the bone marrow and blood. Other populations
      appear to be normal. To the best of our knowledge, this is the first report of B
      lymphopoiesis being undetectable more than 2 years after allogeneic SCT.

PMID- 12235526
TI  - Peripheral blood stem cell transplantation for POEMS syndrome.
AB  - In common with other plasma cell dyscrasias in which a small tumour burden is
      associated with severe clinical symptoms (notably systemic AL amyloidosis) the
      possible benefits of dose intensification are yet to be fully explored in POEMS
      syndrome. One important issue is whether the toxicity of the procedure is
      significantly increased in this group. We report two cases of POEMS syndrome with
      solitary asymptomatic bone lesions treated with high-dose melphalan (200 mg/m(2))
      and peripheral blood stem cell (PBSC) rescue. In both cases there was minimal
      peri-transplant morbidity and a subsequent substantial and maintained improvement
      in the peripheral neuropathy.

PMID- 12235528
TI  - Full chimerism in nonmyeloablative stem cell transplantation in a beta
      thalassemia major patient (class 3 Lucarelli).
AB  - Bone marrow transplantation is the only therapeutic option that can eliminate
      thalassemic disease. Early results indicated that children in class 3 Lucarelli
      had a much worse outcome because of high nonrejection mortality and high
      rejection rate. We therefore tried to investigate a nonmyeloablative stem cell
      transplantation (NST) approach for such a disease in order to reduce mortality
      and rejection. We report here the case of successful NST in a 10-year-old girl
      who had class 3 Lucarelli beta-thalassemia major. The conditioning regimen
      consisted of busulfan, fludarabine, antilymphocyte globulin and total lymphoid
      irradiation. Her GVHD prophylaxis included mycophenolate mofetil and cyclosporin.
      The patient had full donor engraftment without acute and chronic GVHD. She is now
      alive and well and remains disease-free 1 year after transplant.

PMID- 12235527
TI  - Successful treatment of pure red cell aplasia with a single dose of rituximab in
      a child after major ABO incompatible peripheral blood allogeneic stem cell
      transplantation for acquired aplastic anemia.
AB  - Pure red cell aplasia (PRCA) is a well-known although infrequent hematologic
      complication after allogeneic bone marrow transplantation. PRCA occurs in cases
      of major ABO-mismatch between donor and recipient and is believed to be due to
      inhibition of donor erythroid progenitors by residual host isohemagglutinins. We
      report a 10-year-old boy with post-hepatitis aplastic anemia (AA) who developed
      PRCA after HLA-matched familial peripheral blood stem cell transplantation (SCT)
      following conditioning with Cph 200 mg/kg + ATG 90 mg/kg. Granulocyte engraftment
      occurred on day +18, platelet engrafted on day +40, while reticulocytopenia at 0%
      persisted until day +118, and erythroid precursors were totally absent from bone
      marrow. After a single dose of rituximab 200 mg/m(2)administered on day +118 PRCA
      resolved and on day +132 the reticulocytes rose to 5.7%. On day +139 the Hb
      reached 137 g/l and the erythroid lineage in BM increased to 21%. We conclude
      that due to the rapid recovery from PRCA and lack of side effects, rituximab
      should be tried as first-line treatment of PRCA after allo-SCT.

PMID- 12235529
TI  - Diagnosis and monitoring of primary cytomegalovirus infection by antigenemia
      test.

PMID- 12235530
TI  - Foraminal and far lateral lumbar disc herniations: surgical alternatives and
      outcome measures.
AB  - Far lateral disc herniations constitute 7-12% of all disc herniations. They may
      be purely far lateral or extraforaminal in location, located beyond the pedicles,
      or may include intraforaminal and even intracanalicular components. Occurring
      predominantly at the L4-L5 and L3-L4 levels in almost equal numbers, they are
      occasionally noted at L5-S1. Clinical syndromes reflect compression of the
      superiorly exiting nerve root and ganglion; ie an L4-L5 far lateral disc produces
      a L4 root syndrome. Clinical complaints often include severe radicular pain
      accompanied by very positive mechanical signs; Lasegue and reverse Lasegue
      (femoral stretch test) maneuvers. Neurological deficits, including motor, reflex,
      and sensory findings, are seen over 75% of the time. Although conservative
      management is occasionally successful (10%), surgery is usually required. The
      extent of stenosis and attendant degenerative changes dictate whether
      laminectomy, hemilaminectomy or laminotomy are required along with one of several
      facet resection options; full facetectomy, the intertransverse approach, medial
      facetectomy, or an extreme lateral procedure. Postoperatively, patients'
      neurological outcomes based on both surgeon and patient based outcome measures
      (SF-36), were comparable for the different surgical procedures which had been
      based on the individual patient's pathology.

PMID- 12235531
TI  - Decompression of the spinal subarachnoid space as a solution for syringomyelia
      without Chiari malformation.
AB  - STUDY DESIGN: Review and analysis of seven cases of syringomyelia treated
      surgically. OBJECTIVE: To demonstrate the beneficial role of decompressive
      surgery for the altered cerebrospinal fluid (CSF) flow dynamics in syringomyelia
      not associated with Chiari I malformation. A comparison between the pre- and post
      operative syrinx size and CSF flow in the subarachnoid space was made using cine
      mode magnetic resonance imaging (cine-MRI) and then correlated with clinical
      improvement. SETTING: University Hospital, Seoul, Korea. METHODS: Conventional
      spinal MRI and cine-MRI were performed in the region of CSF flow obstruction
      preoperatively in seven patients with syringomyelia not associated with Chiari I
      malformation. The group consisted of one case of syrinx with post-traumatic
      compression fracture, one case of post-traumatic arachnoiditis, two cases of
      holocord syrinx associated with hydrocephalus without Chiari malformation, one
      case of syrinx with post-traumatic pseudomeningeal cyst, one case of post
      laminectomy kyphosis-associated syringomyelia and one case of post-tuberculous
      arachnoiditis syringomyelia. Based on the preoperative cine-MRI, the types of
      surgery appropriate to correct the CSF flow obstruction were chosen:
      decompressive laminectomy-adhesiolysis and augmentation duraplasty in
      arachnoiditis cases, ventriculoperitoneal shunt for hydrocephalus, cyst
      extirpation in pseudomeningeal cyst and both anterior and posterior decompression
      fusion in the case of post-laminectomy kyphosis. A syrinx-draining shunt
      operation was performed in three cases; where the syringomyelia was associated
      with post-traumatic compression fracture refractory to a previous decompression,
      where hydrocephalus was present in which the decompression by
      ventriculoperitoneal shunt was insufficient and where post-traumatic
      arachnoiditis was present in which the decompression was impossible due to
      diffuse adhesion. Change in syrinx size was evaluated with post-operative MRI in
      all seven cases and restoration of flow dynamics was evaluated with cine-MRI in
      three of the cases, two patients with clinical improvement and one patient with
      no change of clinical status, respectively. RESULTS: Four out of seven patients
      showed symptomatic improvement after each decompressive operation. In the
      remaining three cases, reconstruction of the spinal subarachnoid space was not
      possible due to diffuse adhesion or was not the main problem as in the patient
      with syrinx associated with hydrocephalus who had to undergo a shunt operation.
      One of these three patients showed clinical improvement after undergoing
      syringosubarachnoid shunt. A decrease of syrinx size was observed in only two out
      of the five patients who showed clinical improvement after treatment. Of these
      five patients, two patients underwent post-operative cine-MRI and the restoration
      of normal CSF flow dynamics was noted in both patients. Of the remaining two
      patients, one underwent post-operative cine-MRI and there was no change in the
      CSF flow dynamics evident. CONCLUSION: These results suggest that the restoration
      of CSF flow dynamics between the syrinx and the subarachnoid space by
      decompressive operation is more effective than simple drainage of the syrinx
      cavity itself in the treatment of syringomyelia without Chiari malformation.

PMID- 12235532
TI  - Prediction of VO(2peak) in wheelchair-dependent athletes from the adapted Leger
      and Boucher test.
AB  - PURPOSE: :The purpose of this study was to provide a predictive peak oxygen
      uptake ([V]O(2) peak) equation in wheelchair-dependent athletes using the Adapted
      Leger and Boucher test. SUBJECTS AND PROTOCOL: :Fifty-six wheelchair-dependent
      athletes, 47 males and nine females (30.3+/-4 years), underwent a clinical
      examination to assess their anthropometric characteristics: height, mass, body
      mass index (BMI), lean body mass, arm length, and muscular arm volume. They
      performed a deceleration field test to assess the subject-wheelchair resistance
      defined as a mechanical variable, and they then performed the Adapted Leger and
      Boucher test to assess physiological data at maximal exercise ([V]O(2) peak,
      heart rate max) concomitantly with biomechanical (number of pushes) and
      performance variables (maximal aerobic velocity Va(max) and maximal distance).
      The [V]O(2) peak was measured directly using a portable telemetric oxygen
      analyzer. Subjects were then randomly assigned to an experimental group (n=49) to
      determine the predictive equation, and a validation group (n=7) to check the
      external validity of the equation. RESULTS: A stepwise multiple regression with
      [V]O(2) peak (l min(-1)) as the dependent variable led to the following equation:
      [V]O(2) peak=0.22 Va(max) - 0.63 log(age)+0.05 BMI 0.25 level+0.52, with
      r(2)=0.81 and SEE=0.01. Paraplegic subjects with high and low lesion level spinal
      injuries were attributed the coefficient of 1 and 0, respectively. The external
      validity of the equation was positive since the predicted [V]O(2) peak values did
      not significantly differ from directly measured [V]O(2) peak (P>0.05).
      CONCLUSION: We concluded that [V]O(2) peak in wheelchair-dependent athletes was
      predictable using the equation of the present study and the described incremental
      test.

PMID- 12235533
TI  - Perceived exertion and rehabilitation with wheelchair ergometer: comparison
      between patients with spinal cord injury and healthy subjects.
AB  - OBJECTIVES: The purpose of this study was to compare the effects of a
      rehabilitation program on the perceived exertion (PE) and the cardioventilatory
      responses during exercise in healthy people and paraplegics. METHODS: A group of
      seven healthy persons (age 26.6 SD 6.2 years) and one of seven paraplegics (age
      42 SD 15.9 years) participated in a rehabilitation program composed of Square
      Wave Exercise Tests (SWEET) during six weeks. The maximal oxygen uptake, the
      power output (PO), heart rate (HR) and measures of PE using the Borg CR 10 scale
      were investigated during a maximal graded test performed before and after the
      rehabilitation program. During the first SWEET session (SWEET 1) measures of PE
      and HR (base and peak) were also investigated and compared to the last session
      (SWEET 2) of the same absolute workload after the 6 weeks. RESULTS: Statistical
      analysis revealed no significant difference in both groups for PE between the two
      maximal graded tests. However, a significant decrease in the PE values (P<0.01)
      was observed in both groups during the SWEET 2. There was no significant
      difference in maximal HR between the two graded tests, but a significant decrease
      in HR (P<0.0001 for base HR and P<0.001 for peak HR) was observed in SWEET 2
      compared to 1. The maximal tolerated power (MTP) and the peak oxygen uptake
      increased significantly in both healthy and paraplegic groups (P<0.0001 and
      P<0.05 respectively) after the 6 weeks of rehabilitation exercise. CONCLUSION:
      The results of the present study suggest that PE could be used to control the
      exercise intensity during a rehabilitation training program for paraplegics,
      similar to healthy subjects. The increase in the peak oxygen uptake and MTP
      demonstrates the positive effects of the rehabilitation program on the physical
      fitness of the subjects.

PMID- 12235534
TI  - Effects of serotonin 1A agonist on acute spinal cord injury.
AB  - STUDY DESIGN: We evaluated the effects of serotonin (5-HT) agonists on in vitro
      models of spinal cord compressive injury. Evoked potentials in injured rat spinal
      cords (n=24) were recorded during perfusion with 5-HT agonists. OBJECTIVES: To
      evaluate the therapeutic effects of 5-HT agonists on the recovery of compound
      action potentials in injured spinal cords. METHODS: Rat dorsal columns were
      isolated, placed in a chamber, and injured by extradural compression with a clip.
      Conducting action potentials were activated by supramaximal constant current
      electrical stimuli and recorded during perfusion with 5-HT agonists and
      antagonists. RESULTS: After inducing compression injuries, mean action potential
      amplitudes were reduced to 33.9+/-5.4% of the pre-injury level. After 120 min of
      perfusion with Ringer's solution, the mean amplitudes recovered to 62.8+/-8.4% of
      the pre-injury level. At a concentration of 100 micro M, perfusion with
      tandospirone (a 5-HT1A agonist) resulted in a significantly greater recovery of
      mean action potential amplitudes at 2 h after the injury (86.2+/-6.9% of pre
      injury value) as compared with the control Ringer's solution (62.8+/-8.4% of pre
      injury value, P<0.05). In contrast, quipazine (a 5-HT2A agonist) accelerated the
      decrease of amplitude (54.5+/-11.7% of pre-injury value). 5-HT1A and 5-HT2A
      agonist did not consistently alter latencies of the action potentials.
      CONCLUSION: The 5-HT1A receptor agonist was effective for the recovery of spinal
      action potential amplitudes in a rat spinal cord injury model.

PMID- 12235535
TI  - Serum cystatin C as a marker of the renal function in patients with spinal cord
      injury.
AB  - OBJECTIVE: To investigate the relationship between serum cystatin C, serum
      creatinine, and (51)Cr-EDTA-clearance in patients with spinal cord injury.
      SETTING: The Spinal Cord Unit, Viborg-Kjellerup County Hospital. METHODS: Twenty
      four men and seven women aged 20.3 to 68.0 years with motor complete spinal cord
      injury (ASIA A or B) were included. Serum cystatin C was measured by an automated
      particle-enhanced nephelometric immunoassay (Dade Behring), serum creatinine by
      an enzymatic method (Vitros 950), and (51)Cr-EDTA-clearance by a multiple plasma
      sample method. RESULTS: A linear relationship was found between (51)Cr-EDTA
      clearance and the reciprocal values of cystatin C and creatinine. The correlation
      coefficient between (51)Cr-EDTA-clearance and 1/cystatin C was 0.72 compared to
      the correlation coefficient between (51)Cr-EDTA-clearance and 1/creatinine being
      0.26. Comparison of the area under the curves in the non-parametric receiver
      operating characteristics (ROC) plots for serum cystatin C (area under the curve
      (AUC)=0.912; SE=0.065), and serum creatinine (AUC=0.507; SE=0.115) revealed
      significant differences (P-values=0.0005). CONCLUSION: In patients with spinal
      cord injury serum cystatin C is a better marker of the renal function compared to
      serum creatinine.

PMID- 12235536
TI  - Importance of access to research information among individuals with spinal cord
      injury: results of an evidenced-based questionnaire.
AB  - OBJECTIVE: To assess the interests and accessibility of patients with a spinal
      cord injury (SCI) to information in different areas of SCI. SETTING: Spinal
      Program, Toronto Western Hospital, University Health Network. METHODS: An
      interest assessment survey and the SF-36 (short form-36) questionnaire were
      mailed to SCI patients living in the community. The interest assessment examined
      patients' interest in information in many areas related to SCI, their current
      knowledge in these areas and the accessibility of different information formats.
      RESULTS: Fourteen patients (45%) completed the questionnaires. Regardless of
      physical or mental health status, all patients expressed a high level of interest
      in SCI research and clinical trials. An Internet website proved to be the most
      preferred, accessible and comfortable information format for these patients.
      Patients expressed a lower interest in support groups and organizations. Results
      from the SF-36 showed poor social functioning was related to interest in support
      groups, and poor general health perception was related to interest in
      occupational and physical therapy. CONCLUSION: The majority of SCI patients have
      a high interest in accessing SCI research information. The Internet is a
      favorable, comfortable and accessible tool for providing this information and
      will benefit all SCI patients. These results suggest that a significant number of
      patients with SCI would benefit from an accessible Internet-based information
      database that is relevant to the SCI patients population.

PMID- 12235537
TI  - Complications of intermittent catheterization: their prevention and treatment.
AB  - STUDY DESIGN: Literature review to evaluate the complications seen in patients on
      intermittent catheterization (IC) and intermittent self-catheterization (ISC).
      OBJECTIVES: To find the prevalence of most complications seen in patients on IC.
      To study the prevention and the treatment of these complications. SETTING: An
      international literature review. METHODS: Most relevant articles on the subject
      are reviewed. CONCLUSION: Urinary tract infection is the most frequent
      complication in patients performing IC. Catheterization frequency and the
      avoidance of bladder overfilling are amongst the most important prevention
      measures. Asymptomatic bacteriuria does not need to be treated with antibiotics.
      Long-term antibacterial prevention does seem to bear a risk of development of
      bacterial resistance. Previous treatment with indwelling catheters is a risk
      factor for chronic infection and urinary sepsis. Prostatitis is more frequently
      present than often thought. Epididymitis and urethritis are rare. Trauma from
      catheterization occurs regularly, but lasting effects are more limited. However,
      the prevalence of urethral strictures and false passages increases with longer
      use of IC. The use of hydrophilic catheters might be able to lower the urethral
      complication rate but additional proof through comparative studies is needed. The
      most important prevention measures are good education of all involved in IC, good
      patient compliance, the use of a proper material and the application of a good
      catheterization technique.

PMID- 12235538
TI  - Pitfall in insertion of suprapubic catheter in patients with spinal cord
      injuries.
AB  - OBJECTIVE: To report an unusual presentation of a misplaced suprapubic catheter
      (SPC) in a spinal cord injury (SCI) patient. DESIGN: A case report of a SCI
      patient in whom a SPC was 'partially misplaced' in an emergency. SETTING: London
      Spinal Injuries Unit, Stanmore, UK. SUBJECT: A 33-year-old man who sustained a C5
      SCI in a road traffic accident 6 months ago. He had an indwelling urethral
      catheter, which blocked off and repeated attempts to reinsert another one per
      urethra were unsuccessful. MAIN OUTCOME MEASURE: A SPC was inserted in an
      emergency at the bedside, as he developed autonomic dysreflexia. The catheter
      initially drained clear urine but subsequently the flow became intermittent. He
      also started complaining of lower abdominal discomfort. RESULTS: The abdominal
      examination was unremarkable without signs of peritonism. An ultrasound scan of
      the abdomen revealed the eye of the catheter in the bladder but the balloon had
      been inflated in the subcutaneous tissues. It was reinserted under cystoscopic
      control in the operating theatre. CONCLUSION: The insertion of a SPC in a
      neuropathic patient can be a challenge even for an experienced urologist. As
      these patients often have small capacity bladders, the SPC should be inserted
      under cystoscopic control wherever possible. However if they are inserted blindly
      there should be a high index of suspicion for the potential complication of a
      misplaced catheter. The patient should undergo regular abdominal examination and
      an ultrasound scan should be performed as soon as possible for confirmation.

PMID- 12235539
TI  - Retropulsion of intervertebral discs associated with traumatic hyperextension of
      the cervical spine and absence of vertebral fracture: an uncommon mechanism of
      spinal cord injury.
AB  - STUDY DESIGN: Case report of a 68-year-old male who sustained cervical trauma
      following a bodysurfing accident. OBJECTIVE: To describe the pathology of a
      relatively uncommon mechanism of injury involving extradural cord compression
      associated with traumatic disc protrusion and herniation, following a cervical
      hyperextension injury in which there was no vertebral fracture or residual
      subluxation. SETTING: Department of Neuropathology, Royal Perth Hospital, West
      Australia. METHOD: Postmortem pathology report. RESULTS: Evidence of multiple
      ruptures of anterior longitudinal ligament with posterior intervertebral disc
      herniation and three discrete foci of central cord hemorrhage. CONCLUSION:
      Observations are consistent with cervical extension injury and an injury vector
      that involves intense axial loading sufficient to cause multiple disc failures,
      disc herniation and retropulsion leading to extradural disc compression and cord
      hemorrhage.

PMID- 12235543
TI  - [Myoclonic-astatic epilepsy in early childhood: review of clinical signs, EEG
      features, etiology, and therapy].
AB  - Myoclonic-astatic epilepsy in early childhood: review of topical knowledge of
      clinical signs, electroencephalographic characteristics, etiology and therapy.
      The classification of epilepsy in childhood is discussed continuously. On the
      basis of some selected cases, the clinical and electrophysiological
      characteristics of myoclonic-astatic epilepsy in early childhood are described.
      On the one side we describe similarities of this entity and on the contrary side
      variabilities of the individual cases. New molecular results are described as
      possible reasons of the individual course of this disease. The topical options
      regarding therapy are prescribed.

PMID- 12235544
TI  - [Clinical symptoms in 35 children and adolescents with craniopharyngeoma at the
      time of diagnosis].
AB  - AIM: Hormonal deficiencies, visual disturbances, or cerebral symptoms are often
      the symptoms through which craniopharyngiomas (CP) first become clinically
      manifest. As these symptoms can exist for a long period of time various
      specialists are often consulted before the final diagnosis is made. PATIENTS AND
      METHODS: Between the years 1970 and 1998, 37 children and adolescents with CP
      were treated in Erlangen. The documents of 35 patients (22 male, 13 female) were
      evaluated retrospectively. RESULTS: The median age of the children at diagnosis
      was 9,3 years (1,3 - 15,6 years). The most frequently documented symptoms were:
      headache 57 % (median duration 7 months; varying from 1 week to 6 years), visual
      disturbances 45 % (median duration 2 months, range 2 weeks to 10 years), and
      reduced growth 40 % (median duration 1 year, range 3 months to 5 years). On
      average the reported symptoms were present for 15 months (median 5 months, time
      span 1 week to 10 years). CONCLUSION: The clinical symptoms of CP are non
      specific and highly varied. Endocrine disturbances are the primary objective
      finding. Correct interpretation of the symptoms are required for the early
      diagnosis of CP.

PMID- 12235545
TI  - [Clinical and molecular genetic findings in four girls with Rett syndrome].
AB  - We report on four mental retarded girls with typical clinical signs of Rett
      syndrome. Rett syndrome is an X-linked neurodevelopment disorder which develops
      after a period of normal development at the age of 6 to 18 months, affecting 1/10
      000 - 15 000 girls. Recently, the MeCP2-gene encoding the methyl-CpG-binding
      protein 2 has been shown to be mutated in 80 percent of girls with Rett Syndrome,
      studied so far. In our patients with Rett syndrome two common mutations of the
      MeCP2-gene, R168X (n=2) and T158M were found. In the 4th patient a novel
      "missense" mutation R294G was identified.

PMID- 12235546
TI  - Butane abuse associated Encephalopathy.
AB  - Butane contained in household products is easily available for abuse and is not
      subject to legal prosecution in Germany. The toxicological properties of butane
      mainly affect the heart and the CNS. A serious pathophysiological mechanism is
      asphyxia due to the replacement of oxygen by butane. We report an abusive butane
      inhalation in a 15-year old girl, resulting in cardiopulmonary resuscitation and
      subsequent development of severe brain damage. After reviewing the medical
      literature and questioning German toxicological information centres it became
      obvious, that abuse of butane is an increasing problem. We give an survey about
      the complications associated with butane intoxication.

PMID- 12235547
TI  - [Congenital Hyposplenia with multiple additional anomalies: a variant of the
      Ivemark Syndrome].
AB  - We report an 18-months-old boy with congenital spleen hypoplasia and
      cardiovascular defects. Besides, several minor clinical manifestations such as
      facial anomalies, hypospadia glans penis, agenesis of the corpus callosum and
      iris anomalies were observed. A partial or complete lateralisation defect could
      be excluded. The patient's phenotype comprises a previously undescribed
      combination of major and minor clinical features of the Ivemark syndrome. The
      case indicates that a common genetic defect might be the cause of this syndrome,
      which shows a variable expression.

PMID- 12235548
TI  - [Transcatheter occlusion of the persisting arterial duct].
AB  - BACKGROUND: Transcatheter occlusion of the persisting arterial duct (PDA) is
      feasible using different techniques like coil-embolization (CE), Rashkind PDA
      occluder (Rash), Amplatzer Duct Occluder (ADO). Comparative studies with this
      devices in relation to the size of the PDA and the device are missing. Aim of
      this study was to evaluate the different systems at the own patient population.
      PATIENTS AND METHODS: From 1993 to 12/2001 transcatheter occlusion was attempted
      in 92 patients aged 4,13 years (range 0,07 to 14,39 years) using CE, Rash or ADO.
      All patients received echocardiographic examinations 24 hours before and after
      intervention, after 3, 6, and 12 months and than yearly. RESULTS: 91/92 PDAs
      could be successfully closed by 97 interventions. There were 63 CE, 25 Rash and 9
      ADO performed. Primary closure rate was 75 % for Rash, 80 % for ADO and 80,8 %
      for CE (n. s.) and after 6 months 88 % for Rash, 92,3 % for CE and 100 % for ADO
      (p < 0,001), although the size of the PDA increased significantly from CE (2,14 +
      1,1 min) to Rash (3,2 +/- 1,3 min) to ADO (4,9 +/- 1,9 min) (p < 0.05). In 6/7
      pts with residual shunts complete occlusion could be achieved by second
      intervention. CONCLUSION: In dependency of the size of the PDA and the right
      choice of the occluder almost all PDAs are closable with transcatheter
      techniques.

PMID- 12235549
TI  - [Influence of intertrochanteric varisation osteotomy on the gait of children with
      Perthes disease].
AB  - BACKGROUND: The purpose of this study was to investigate possible effects of
      intertrochanteric varisation osteotomy on the gait of children with Perthes
      disease. PATIENTS: Clinical and radiographic examinations and gait analysis were
      conducted on 50 children. METHOD: Gait analysis was conducted using the GANGAS
      system. RESULTS: Despite predominantly very good or good results shown by the
      clinical and radiographic examinations, gait analysis detected various functional
      deficits. CONCLUSIONS: The examinations show that for the group of patients
      described, gait analysis is a valuable method of recording functional deficits
      and early recognition of the need for postoperative, physiotherapeutic treatment,
      thus helping to avoid chronificating alterations of the gait and, consequently,
      potential secondary damage.

PMID- 12235550
TI  - [Severe 46,XY virilization deficit due to 17beta-hydroxysteroid dehydrogenase
      deficiency].
AB  - BACKGROUND: 17beta hydroxysteroid dehydrogenase deficiency is a presumable rare
      cause for a severe virilization disorder in children with 46,XY karyotype due to
      a defect in the testicular testosterone biosynthesis from androstenedione.
      PATIENT: We report on a 14 year old child with 46,XY karyotype with a
      predominantly female phenotype. RESULTS: Hormonal analysis showed low values for
      androstenedione and testosterone before and after stimulation with human
      chorionic gonadotropin, however, the androstenedione/testosterone ratio was
      elevated. Molecular genetic analysis proved the diagnosis of 17beta
      hydroxysteroid dehydrogenase deficiency due to a homozygous mutation (325+4 A-T)
      in the HSD17B3-gene, which leads to an aberrant splicing process. CONCLUSIONS:
      This case demonstrates that in addition to a meticulous steroid analysis a direct
      molecular genetic analysis can be helpful in the diagnosis of 17beta
      hydroxysteroid dehydrogenase deficiency.

PMID- 12235551
TI  - [Solid-pseudopapillary tumor of the pancreas in a 9-year-old girl].
AB  - Solid-pseudopapillary tumor of the pancreas constitutes a very rare benign or low
      grade malignant lesion occurring most commonly in young women and girls. It was
      first described by Frantz. Local infiltration, distant metastasis and recurrence
      are very rare. Until today, the histogenetic origin of the tumor cell remains to
      be elucidated. In 1996, solid-pseudopapillary tumor of the pancreas was
      introduced in the World Health Organization (WHO) classification of tumors of the
      exocrine pancreas. Our case report--like a recently published work by Lange et
      al.--intends to underline the significance of solid-pseudopapillary tumor in the
      differential diagnosis of a pancreatic mass.

PMID- 12235552
TI  - [Gonarthritis due to Salmonella enteritidis in a patient with systemic lupus
      erythematosus].
AB  - Extraintestinal manifestations of Salmonella infection occur more frequently in
      immunocompromised patients than in healthy persons. About 25 % present as septic
      arthritis. Particularly patients with SLE are predisposed. We report a case of a
      16-year old girl with systemic lupus erythematosus who developed septic arthritis
      of the left knee. Delayed diagnosis because of similar symptoms of arthritis due
      to lupus and purulent arthritis led to a destruction of the joint despite
      systemic antibiotic treatment. Seven months later an endoprosthesis was implanted
      with good outcome. Early diagnosis, adequate antibiotic therapy and, if
      necessary, surgical intervention are essential for successful treatment. In
      patients with SLE suffering from fever or arthritis it is necessary to think of
      infections particularly due to salmonella.

PMID- 12235554
TI  - [Imaging in rheumatology].
AB  - SUMMARY: Conventional radiography, ultrasonography, scintigraphy, computed
      tomography, and magnetic resonance imaging (MRI) are important diagnostic tools
      in rheumatology additional to clinical investigation. Radiography provides
      information both of the juxtaarticular and the abarticular bone. It is relevant
      in the diagnosis of rheumatoid arthritis, osteoarthritis, spondylarthropathies,
      and osteoporosis, and for the investigation of other regions like the thorax.
      Sonography is superior to radiography to delineate soft tissue structures such as
      effusions, tenosynovitis, tendinitis, paratendinitis, bursitis, and soft-tissue
      tumors, but also to evaluate bone surfaces. It helps to perform injections and
      punctures. Furthermore it is a new diagnostic tool for the diagnosis of temporal
      arteritis, Takayasu's arteritis, and Sjogren's syndrome. Echocardiography,
      abdominal and pleural sonography are also frequently used. MRI is useful to
      detect soft tissue lesions and bone lesions. It is helpful to depict synovial
      membrane, tendon, tendon sheaths, ligaments, cartilage, destructive joint
      processes, and rupture of synovial cysts. MRI is an established imaging technique
      in diagnosis of sacroiliitis and cervical arthritis as well as in diagnosis of
      osteonecrosis. It is an important diagnostic modality for demonstrating early
      arthritis. MRI is also of interest in diagnosis of neurological disorders of
      connective tissue diseases or vasculitis in rheumatology. Bone scintigraphy is an
      established imaging technique in diagnosis of skeletal diseases as well as in
      diagnosis of tumors. "Hot spots" are seen in locations of high bone turn over.
      Scintigraphy is also helpful to localize or exclude inflammation.

PMID- 12235553
TI  - [Induction of remission with infliximab in therapy-refractory Wegener's
      granulomatosis - Follow-up of six patients].
AB  - BACKGROUND AND QUESTION: The prognosis of patients with Wegener's granulomatosis
      (WG) refractory to standard treatment for the induction of remission
      (cyclophosphamide and steroids) has been poor so far. We report on the results of
      the follow-up of six patients refractory to the standard regimen (Fauci's scheme)
      with progressive, imminent visual loss, pulmonary and renal involvement,
      respectively. How long can remissions be successfully maintained with anti-TNF
      alpha-antibody infliximab? What side effects occur? PATIENTS AND METHODS:
      Patients received infliximab (3 mg/kg) in addition to standard therapy with
      cyclophosphamide and steroids. Intervals between the first two infliximab
      infusions were 2 weeks, thereafter 4 weeks. Based on the impression of higher
      efficacy patients received 5 mg/kg infliximab for subsequent infusions. RESULTS:
      Remission was induced after 4-6 infliximab infusions in five patients. Remission
      has been maintained in four patients for 16-26 months. After 12 months a
      pulmonary relapse occurred in one patient, who received azathioprine for the
      maintenance of remission. Infliximab was stopped in another patient because of a
      suspected infection. In the light of high cumulative cyclophosphamide doses (100
      g/275 g) and cyclophosphamide induced hemorrhagic cystitis, infliximab was added
      to azathioprine in the two patients with a pulmonary relapse and protrusion of
      the eye with imminent visual loss, respectively. Remission was induced in both
      patients. A carcinoid of the bronchus was diagnosed in one patient after 12
      months in remission. CONCLUSION: Infliximab means a new therapeutic option and
      offers better perspectives for a patient group with previously bad prognosis.

PMID- 12235555
TI  - Predictors of the risk of mortality in neurofibromatosis 2.
AB  - To evaluate clinical and molecular predictors of the risk of mortality in people
      with neurofibromatosis 2 (NF2), we analyzed the mortality experience of 368
      patients from 261 families in the United Kingdom NF2 registry, using the Cox
      proportional-hazards model and the jackknife method. Age at diagnosis,
      intracranial meningiomas, and type of treatment center were informative
      predictors of the risk of mortality. In Cox models, the relative risk of
      mortality increased 1.13-fold per year decrease in age at diagnosis (95%
      confidence interval [CI] 1.08-1.18) and was 2.51-fold greater in people with
      meningiomas compared with those without meningiomas (95% CI 1.38-4.57). The
      relative risk of mortality in patients treated at specialty centers was 0.34
      compared with those treated at nonspecialty centers (95% CI 0.12-0.98). In a
      separate model, the relative risk of mortality in people with constitutional NF2
      missense mutations was very low compared with those with other types of mutations
      (nonsense or frameshift mutations, splice-site mutations, and large deletions),
      but the CI could not be well quantified because there was only one death among
      people with missense mutations. We conclude that age at diagnosis, the strongest
      single predictor of the risk of mortality, is a useful index for patient
      counseling and clinical management (as are intracranial meningiomas). To ensure
      optimal care, we recommend that people with NF2 be referred to specialty
      treatment centers.

PMID- 12235556
TI  - [Buspirone chlorhydrate in the treatment of cerebellar ataxia].
AB  - AIM: To evaluate the efficiency of buspirone chlorhydrate in a group of patients
      who all presented sporadic or family primary cerebellar ataxia. PATIENTS AND
      METHODS: In this open label study of addiction, the following eligibility
      criteria were used: 1) Clinical: primary cerebellar ataxia; 2) Radiological:
      nuclear magnetic resonance showing pure cerebellar cortical atrophy; 3) Age: over
      20 years old. Any patient with a history of food deficiency, alcoholism,
      neoplasic, infectious, degenerative and vascular diseases was excluded from
      taking part in the study. Of the 20 patients examined initially, 18 met the
      eligibility criteria, and of these 11 reached the end of the study, although drop
      outs were not related to treatment. Four patients had been diagnosed as suffering
      from cerebellar cortical atrophy of the sporadic type and the remaining seven had
      a family type cerebellar cortical atrophy. All the patients were thoroughly
      evaluated and received scores both at the beginning and at the end of the study,
      according to the modified Massaquoi scale for clinical evaluation of cerebellar
      functioning, and the Hamilton Anxiety Scale. They were all administered buspirone
      chlorhydrate in doses that progressively increased by 5 mg/month over a total
      period of 12 months. The maximum dose was considered to be 1 mg/kg body weight,
      without exceeding 60 mg. The increase in dosage was stopped if it was not well
      tolerated by the patient

PMID- 12235557
TI  - [The potential P300 in the evaluation of the side effects of
      dexchlorpheniramine].
AB  - INTRODUCTION: The antihistamine chlorpheniramine presents multiple adverse side
      effects on the central nervous system. In earlier work it has been observed that
      a dose equal to the one used in this study alters the evoked potentials PN
      (processing negativity) and MMN (mismatch negativity), which are, respectively,
      indicators of selective attention and of an automatic mechanism for detecting
      changes in auditory stimulation. AIMS. The aim of the present study was to
      evaluate the effects of a single 4 mg dose of dexchlorpheniramine on the evoked
      potential P300, to enable us to better define its effects on the central nervous
      system. Subjects and methods. Using the double blind procedure, half a sample
      consisting in 20 subjects was administered 4 mg of dexchlorpheniramine and the
      other 10 received placebo. 150 minutes after ingestion the potential P300 was
      recorded using an active oddball paradigm. Likewise, efficiency in detecting
      target stimuli was also evaluated. RESULTS: results show that a single 4 mg dose
      of dexchlorpheniramine does not alter P300 nor efficiency in detecting target
      stimuli. CONCLUSIONS: Results show that the dose used has no effect on voluntary
      processes involving the categorization of target stimuli nor on their detection.
      However, the alteration of other attentional mechanisms observed in previous work
      using the same doses suggests that it would be advisable to employ different
      evoked potential paradigms in the evaluation of the side effects other active
      principles or psychoactive substances have on auditory attention.

PMID- 12235558
TI  - [Neuropsychological deficit in Parkinson's disease. Its relation with clinical
      variables].
AB  - INTRODUCTION: A correct diagnostic approach to the problem of Parkinson s disease
      dementia must be based on a thorough clinical history, with a longitudinal vision
      of the process, in which motor, behavioural, cognitive and systemic aspects of
      the disease and the degree of disability produced all have to be taken into
      consideration. Thus, after a meticulous neurological examination, careful
      neuropsychological evaluation is required to try and typify and quantify the
      deficits and the pattern of cognitive deterioration. Since cognitive alterations
      may occur during the first stages of the disease, the patient should be submitted
      to a neuropsychological exploration from the initial phases onwards, and then
      followed by longitudinal controls. AIMS. In an attempt to evaluate and determine
      the neuropsychological deficits associated with this disorder, we used an
      exhaustive neuropsychological battery which enables us to perform an in depth
      examination of the different neuropsychological functions. Our aim is also to
      link the neuropsychological performance of these patients with different clinical
      variables (years of schooling, evolution time, intensity, age of onset, motor
      alterations, depression and dopaminergic treatment). PATIENTS AND METHODS: Our
      sample was made up of 50 subjects divided into two groups according to their
      neurological diagnosis: subjects with Parkinson s disease (PD) and a control
      group. RESULTS: A significant decrease was found in the scores obtained in some
      of the tests by subjects with PD compared with subjects from the control group.
      CONCLUSIONS: In agreement with current research and our own results, we suggest
      that idiopathic PD is not accompanied by dementia, but by just certain specific
      deficits related with cortical functions, mainly in the frontal lobe. The
      dementia that develops in very old patients and those with a long evolution is
      more related with age than with the intensity of the symptoms of Parkinson.

PMID- 12235560
TI  - [Opsoclonus myoclonus syndrome: how long are we going to go on researching?].
AB  - INTRODUCTION: Opsoclonus myoclonus is a rare neurological syndrome affecting
      children and adults, and which is characterised by a sudden onset of chaotic eye
      movements and myoclonias. In children it generally appears before the age of
      three as a parainfectious or paraneoplasic process; the type of tumour most
      frequently associated with this syndrome is the neuroblastoma. CASE REPORT: We
      report the case of a 22 month old girl who, after a febrile syndrome probably
      caused by a virus, began to present myoclonias in the upper and lower limbs,
      opsoclonus, a marked ataxic gait and extreme irritability. After ruling out
      neoplasia, oral corticotherapy was started and the neurological picture gradually
      improved. CONCLUSION: By reporting this clinical picture, our intention is to
      make the particular aspects of this neurological condition known, and highlight
      the need for neoplasias to be detected in time and for early treatment in order
      to prevent sequelae, especially when it appears as a paraneoplasic syndrome.

PMID- 12235559
TI  - [Magnetic Resonance in children with dyskinetic cerebral palsy secondary to
      perinatal injury].
AB  - INTRODUCTION: The incidence of perinatal factors in the dyskinetic cerebral palsy
      (DCP) is high. The introduction of the magnetic resonance (MR) has improved our
      understanding of the pathophysiology and early diagnosis of injury. OBJECTIVE:
      Review the clinical characteristics of a group of patients with DCP and the
      appearance of their MR. PATIENTS AND METHODS: Retrospective study of 20 patients
      with DCP from 37 weeks of gestational age and perinatal injury with MR done.
      RESULTS: The perinatal injury was: fetal distress (15 cases), severe
      hyperbilirubinaemia (1 case) and neurological symptoms of unknown origin (3
      cases). From the 15 patients with fetal distress, 10 had clinical manifestations
      of neonatal hypoxia ischemia. The rest were clinical healthy. Seventeen patients
      had abnormal MR. Four of these had fetal distress without neonatal clinical
      manifestations. MR findings show high intensity areas on T2 weighted images in
      the nucleus thalamus in 6 cases, putamen in 4, thalamus and putamen in 1,
      thalamus and pallidus in 2, thalamus and lenticular in 3 and in the lenticular
      alone in one case. In 5 cases hipointensity areas on T1 weighted images at the
      same sites were identified and in 1 case prolongation of T1. In the child whose
      CDP was caused by severe hyperbilirubinaemia the MR was normal. CONCLUSIONS: The
      fetal distress occurring late in labour without neonatal hipoxic ischemic
      manifestations can precede the developmental of DCP. Our observations support
      that in CDP resulting from perinatal injury the MR shows characteristic focal
      abnormalities in the basal ganglia (putamen and thalamus).

PMID- 12235561
TI  - [Amaurosis fugax as the sole manifestation of a dural arteriovenous fistula].
AB  - INTRODUCTION: Ophthalmologic disorders caused by arteriovenous malformations
      (AVM) are generally related with alterations in the cavernous sinus or
      papilloedema. However, the appearance of amaurosis fugax (AF) as the sole
      clinical manifestation of an AVM has very rarely been reported in the literature.
      CASE REPORT: We present the case of a 64 year old male patient who displayed
      recurring episodes of temporary monocular blindness (AF) as a consequence of the
      haemodynamic disorders triggered off in the course of a dural AVM. DISCUSSION:
      The arteriovenous fistula, located in the anterior fossa, gives rise to theft
      phenomena in the region of the arteries that nourish the retina and trigger
      episodes of AF of an essentially haemodynamic nature.

PMID- 12235562
TI  - [Weston Hurst acute haemorrhagic leukoencephalitis. Neuropathological study of
      one case].
AB  - INTRODUCTION: Acute hemorrhagic leukoencephalitis (AHL), or Hurst disease is a
      rare, usually fatal, disease, probably due to an autoimmune cross reaction
      against myelin antigens present in the central nervous system, and which forms a
      spectrum of post infeccious demyelinating diseases with acute disseminated
      encephalomyelitis. CASE REPORT: The patient was a 21 year old female who
      presented with an acute encephalopathy and generalized seizures following a 15
      day febrile syndrome attributed to amygdalitis; a laboratory work up, including
      CSF, was non diagnostic, and a brain CT scan revealed diffuse cerebral edema.
      After 12 days the patient died from nosocomial pneumonia and multi organ failure;
      neuropathological examination of the brain confirmed the diagnosis of Hurst acute
      hemorrhagic leukoencephalitis, with a weak perilesional inflammatory reaction,
      unlike the usual picture in AHL. DISCUSSION: AHL should be a part of the
      differential diagnosis of acute encephalopathic diseases, particularly if
      preceded by systemic infections. The atypical laboratory findings, and the
      impossibilty of performing a brain MRI were obstacles to the diagnosis in this
      case. The relative paucity of the perivascular infiltrate is an atypical finding,
      and could be due to apoptotic clearance of the inflammatory cells, as has been
      described in other autoimmune demyelinating diseases.

PMID- 12235563
TI  - [Subdural empyema secondary to sinusitis: four pediatric cases].
AB  - INTRODUCTION: Perinasal sinus infections is a common and benign condition in most
      pediatric cases. Because of the widespread use of antibiotics, intracranial
      extension of sinusitis is rarely seen today. Nevertheless, the clinician must be
      aware of the gravity of this condition, because late recognition and delay in
      treatment can increase mortality and morbidity. The authors made a retrospective
      study of pediatric patients admitted to Garcia de Orta Hospital between 1996 and
      2001 with the diagnosis of subdural empyema and sinusitis. CASE REPORTS: Four
      patients were identified, with ages between 9 and 13 years. Prodromal
      manifestations of sinusitis were present in all, followed several days later by
      headaches, fever, vomiting and neurological abnormalities. Two patients presented
      in the emergency department with an acute confusional state and a non convulsive
      status epilepticus. The other two patients had a longer duration of disease,
      severe deterioration of consciousness and focal neurologic signs. Medical
      treatment was started in all cases at admission, but none improved significantly
      before being submitted to surgical intervention, which was repeated several times
      in two patients. Streptococcus milleri and anaerobic organisms were isolated.
      There was no mortality and global evolution was favorable, with a median follow
      up of 32 months. CONCLUSIONS: Clinical presentation of subdural empyema can be
      relatively inespecific, requiring a high degree of suspicion. Facing a young
      adolescent with fever of unknown origin associated with any neurological
      abnormality and previous history of sinusitis, neuroradiological investigation
      shoul be asked. Early diagnosis and treatment are the mainstays of successful
      outcome.

PMID- 12235564
TI  - ["Top-of-the-basilar" syndrome and Chagas' disease].
AB  - INTRODUCTION: As a chronic chagasic myocardiopathy, Chagas disease (CD) may give
      rise to cardiac insufficiency, arrhythmias, thromboembolism and stroke. Occlusive
      vascular disease of the rostral portion of the basilar artery or of its emergent
      branches may cause ischemia and necrosis in different areas of the midbrain,
      thalamic nuclei, cerebellum and occipital lobe. CASE REPORTS: We describe four
      patients (three males and a female, the average age being 54 years) with positive
      chagasic serology (indirect immunofluorescence and hemagglutination) and
      suffering from CD and top of the basilar syndrome. All of them underwent tests to
      determine proteins C and S, antithrombin III, factor V Leiden, and lupic
      anticoagulant, as well as being submitted to explorations using electrocardiogram
      (ECG), echocardiogram, carotid and transcranial echo Doppler, computerised
      tomography (CAT) and magnetic resonance imaging (MRI). RESULTS: The coagulopathy
      studies were normal or negative in the four patients. We also describe the
      findings from the electrocardiograms (blockage in right branch, two cases;
      auricular fibrillation, one case; repolarization disorder, one case) and the
      echocardiograms (left ventricular dysfunction, two patients; apical aneurysm, one
      patient; mural thrombus, one patient). Neuroimaging revealed one case of each of
      the following infarctions: bilateral thalamic, bilateral cerebellar and
      occipital, cerebellar, thalamic mesencephalic and occipital, and thalamic
      mesencephalic and occipitotemporal. CONCLUSIONS: In a patient with positive
      chagasic serology, with or without findings in the ECG and in the
      electrocardiogram that can be put down to a cardioembolic source, a vascular
      syndrome produced by occlusion of the distal basilar artery suggest a
      cardioembolism. We recommend secondary anticoagulation because of the high risk
      of recurrence.

PMID- 12235565
TI  - [Pharmacological treatment of Korsakoff's psychosis: a review of the literature
      and experience in two cases].
AB  - INTRODUCTION: Korsakoff s psychosis (KP) is a relatively frequent pathological
      condition in our community that has been infradiagnosed. The most common cause is
      chronic alcohol consumption, although it can be brought about by other
      aetiologies accompanied by vitamin deficiencies. The lack of thiamine entails an
      alteration in the synthesis of neurotransmitters, which provides the
      neurochemical foundation for the specific cognitive impairment that defines the
      syndrome. AIMS: To evaluate the application of pharmacological treatments, in
      accordance with the neurochemical disorders described in the literature, and
      report our experience in two cases treated with anticholinesterases. CASE
      REPORTS: 1) Female aged 47, with a history of addiction to alcohol. Following
      Wernicke s encephalopathy, which improved with parenteral thiamine, she presented
      a memory disorder compatible with KP. After two months treatment with donepezil,
      a cognitive improvement was observed in the neuropsychological tests. 2) Male
      aged 77, who presented KP a month after being diagnosed and treated for a post
      encephalitic vasculitis caused be varicella zoster virus. His cognitive and
      functional condition improved after 3 months treatment with donepezil. DISCUSSION
      AND CONCLUSIONS: There are not enough studies in the literature with
      representative samples that consider the effects of thiamine or of other forms of
      treatment on cognitive impairment in KP. Noradrenaline, serotonin, glutamate and
      acetylcholine have been proposed in the pathogeny of the syndrome. Based on
      experiences gained in cholinergic disorders, two cases responded to treatment
      with donepezil. Effective treatment must be based on a combination of
      aetiological and pharmacological treatment, and cognitive rehabilitation.

PMID- 12235566
TI  - [Long QT syndrome presented as epilepsy].
AB  - INTRODUCTION: Long QT syndrome is characterised by an alteration in cardiac
      repolarisation that brings about ventricular arrhythmias. The resulting cerebral
      hypoxia leads to fainting and convulsions that, in up to 10% of cases, are
      interpreted as epilepsy. CASE REPORT: We report the case of a patient of
      paediatric age who was affected by an isolated presentation of congenital long QT
      syndrome, which had initially been diagnosed as idiopathic epilepsy, and who
      suffered a sudden loss of consciousness while doing exercise. The initial
      electrocardiographic monitoring revealed a ventricular tachycardia in torsades de
      pointes, which was reversed by advanced cardiopulmonary revival manoeuvres. At 12
      days after admission, there was an absence of electrical brain activity and brain
      death resulted. CONCLUSION: The high mortality among symptomatic patients
      affected by long QT syndrome and the effectiveness of the treatment highlight the
      importance of a correct diagnosis. A detailed clinical history and an
      electroencephalogram with a simultaneous electrocardiogram (ECG) recording,
      together with continuous EEG recording for 24 hours, with the manual evaluation
      of the corrected QT, would all help in the identification of unsuspected cases. A
      complete study of the family, including the possible associated mutations, could
      be a new form of early diagnosis.

PMID- 12235567
TI  - [Reflex epilepsy from hot water: a new case and review of the literature].
AB  - INTRODUCTION: In approximately 5% of epilepsy patients, seizures are triggered
      off by a specific sensory stimulus, in other words, they have reflex epilepsies.
      Among these, seizures triggered off by hot water are exceptional, and especially
      so in our community as nearly all the cases have been reported as occurring in
      India. CASE REPORT: Our case involves a 2 year old girl who, from the first weeks
      onwards, presented bouts of paleness, hypotonia and loss of consciousness when
      her head came into contact with hot water. The findings from clinical,
      neurophysiological and neuroimaging studies are described and there was a good
      response to treatment with valproate. DISCUSSION: The induction of epileptic
      seizures by immersion in hot water has only rarely been reported in western
      countries. Its physiopathology remains unknown but genetic factors that determine
      an alteration in cranial thermoregulation seem to be involved. With similar
      clinical and electroencephalographic characteristics in patients, the prognosis
      is usually favourable because of a good response to pharmacological treatment and
      the tendency toward spontaneous remission of the seizures.

PMID- 12235568
TI  - [The role of the mitochondrial permeability transition pore in neurodegenerative
      processes].
AB  - AIMS: To review the role played by the mitochondrial permeability transition pore
      (MPTP) in different physiological and pathological processes. METHOD: Both
      genetic and functional alterations in mitochondria can lead to errors that
      trigger programmed cell death, which in turn give rise to a number of diseases
      that affect the nervous system. Over the last few years the mitochondrion has
      been seen as the link between the different signalling pathways involved in some
      degenerative processes. The mitochondrion seems to play an important part in the
      cellular decision making that leads, irreversibly, toward the execution phase in
      cellular death processes. This being the case, the action would be mediated by
      the permeability of its membranes, through the formation of the mitochondrial
      permeability transition pore, and would involve phenomena such as the dissipation
      of the mitochondrial electrochemical potential and the release of substances from
      within it. These substances include apoptosis inducing factor (AIF), apoptosis
      protease activating factor 1 (apaf 1), cytochrome c and members of the protease
      family: the caspases. These alterations have been described in neurodegenerative
      pathologies such as Alzheimer s and Parkinson s disease, amyotrophic lateral
      sclerosis and transmissible spongiform encephalopaties. CONCLUSIONS: Designing
      pharmaceutical products capable of interfering with the functions of MPTP would
      allow a better therapeutic approach in neurological pathologies.

PMID- 12235569
TI  - [The usefulness of dopaminergic drugs in traumatic brain injury].
AB  - OBJECTIVE: To review the bibliography indexed in MEDLINE so as to assess and/or
      compare the usefulness and indications of dopaminergic drugs in both cognitive
      and motor disorders due to head injuries (traumatic brain injury). DEVELOPMENT:
      Lesions due to head injuries cause both focal and diffuse cerebral damage which
      lead to neuropsychological and motor deficit. It is clear that motor alterations
      cause major physical disability, but neuropsychological alterations affect
      cognitive behaviour and emotional aspects which are very disabling and seriously
      affect both the patient and his family and also his return to social, family and
      working life. There is a wide range of drugs available to assist in the
      improvement or recovery of the patient. Some of the most important of these drugs
      are the dopaminergic agents, due to the importance of dopamine for proper frontal
      cerebral area function. CONCLUSIONS: This study confirms the indications for the
      use of dopaminergeric drugs when trying to improve or accelerate recovery from
      cognitive deficits in patients with traumatic cerebral damage. However, it is
      important to note that, in view of the complexity of cognitive function and the
      mechanisms of their recovery, it will be necessary to make randomized, double
      blind, prospective studies with a control group (if possible) so as to determine
      the real part played by these drugs in the recovery process of patients with
      traumatic brain damage.

PMID- 12235570
TI  - [Occupational therapy in neurology].
AB  - AIMS: To review the fundamentals of occupational therapy (OT) and to present its
      possible contributions in the field of neurological rehabilitation. DEVELOPMENT:
      As its name suggests, OT is a form of treatment that makes use of occupations.
      Furthermore, occupation is a purpose itself, since OT seeks to adapt the
      individual to the occupation and the occupation to the individual. The postulates
      on which OT rests are: 1. The occupational nature of human beings, 2. Human
      dignity, and 3. A dual therapeutic approach both focal and global. OT acts not
      only on the individual but also on the environment surrounding him or her.
      Neurology is one of the most important fields of application for OT, as patients
      suffering from neurological illnesses are often limited in their ability to
      perform activities of daily living. OT attempts to diminish or compensate for
      cognitive, perceptive or motor deficiencies so that the neurological patient may
      reach the highest degree of functioning and independence. Although up to now the
      efficiency of OT has not been evaluated in a systematic way, there are some
      studies that support its clinical usefulness in certain neurological disorders,
      such as cerebrovascular diseases, dementias and multiple sclerosis. CONCLUSION:
      OT can increase the independence and quality of life of neurological patients.
      New studies are needed to prove the efficacy of OT in different disorders and to
      analyse its financial implications.

PMID- 12235571
TI  - [Immunosuppressants and multiple sclerosis].
AB  - AIMS: Technological progress, improvements in the design of clinical trials and
      in MRI have led to a great variety of therapeutical approaches in dealing with
      multiple sclerosis (MS), some of which have been successful while others less so,
      despite promising results from animal models. DEVELOPMENT: In this paper we
      review the present state of therapy with immunosuppressants in MS and special
      attention is paid to trials conducted with cladribine, linomide, sulfasalazine,
      ciclophosphamide, mitoxantrone, cyclosporine A and azatioprine. CONCLUSION:
      Severe, unspecific immunosuppression lowers the anatomopathological and clinical
      activity of the disease, with slight improvements in the seizure rates and the
      MRI. While no effects have been found on the progression, serious short and long
      term side effects have been observed which, in some cases, prevent it from being
      administered. However, it is true that proof of the efficiency of these products
      may not have been possible owing to methodological problems they might be more
      useful alone or in combination with immunomodulators.

PMID- 12235572
TI  - [Neurosyphilis: forms of presentation and clinical management].
AB  - INTRODUCTION AND AIMS: Neurosyphilis results from the infection of the central
      nervous system by Treponema pallidum. It causes diverse clinical pictures which
      are occasionally similar to other, better known neurological diseases. In this
      paper our aim is to offer a global clinical vision of this entity by reviewing
      the different forms it can take and its diagnostic and therapeutic management.
      DEVELOPMENT: The forms of presentation of neurosyphilis can be grouped in two
      categories: early (asymptomatic, meningeal and meningovascular neurosyphilis) and
      late (progressive general paralysis and tabes dorsalis). Other less important
      forms, such as gummas, ocular forms, syphilitic amyotrophy or hypoacusis, have
      also been described. Diagnosis is complex and is based on the study of the
      cerebrospinal fluid. Given the difficulty involved in performing an accurate
      diagnosis, different criteria have been developed in which T. pallidum serology
      plays a key role. The most effective treatment is penicillin, although on
      occasions it may have no effect and we therefore recommend clinical and fluid
      analysis follow ups. Lastly, we describe the changes in incidence and clinical
      presentation, and the complications that may arise in diagnosis when HIV carrying
      patients also suffer from this disease. CONCLUSIONS: Neurosyphilis is a disease
      that still occurs nowadays and, due to its clinical polymorphism, must be borne
      in mind as a differential diagnosis in a number of neurological and psychiatric
      illnesses. This, together with the fact the serological tests are difficult to
      interpret and its irregular response to the usual treatment, makes it difficult
      to manage and means that the neurologist must have a thorough knowledge of the
      disorder.

PMID- 12235573
TI  - [Do we defend a brain oriented view of death?].
AB  - AIMS: To propose a new formulation of death based on the mechanisms involved in
      consciousness generation in human beings. DEVELOPMENT: Any complete formulation
      of death must include three different elements: a definition of death, its
      anatomofunctional substratum and the tests required to diagnose death. The three
      brain oriented formulations of death are: the whole brain, the brain stem, and
      the neocortical formulations of death. In this paper I review and discuss each of
      these formulations, and I propose a new formulation about human death based on
      the physiopathological mechanisms involved in the generation of consciousness.
      This contains two physiological components: arousal and awareness. Since the
      structures of the brain stem, the diencephalon and the cerebral cortex interact
      to generate consciousness, it would be a mistake to make a rigid distinction
      between their functions from the point of view of waking and content. Important
      interconnections between the brain stem, other subcortical structures and the
      neocortex give rise to both components of consciousness. The generation of
      consciousness, then, is based on the anatomy and the physiology of pathways
      throughout the whole brain. None of the three formulations above is wholly
      satisfactory. CONCLUSION: I propose a new formulation of death that identifies
      consciousness as the most important function of the organism, because it provides
      the essential human attributes and the highest level of control within the
      hierarchy of integrating functions of the organism

PMID- 12235576
TI  - [Experimentation with human stem cells].

PMID- 12235575
TI  - [Intrauterine spinal cord injury resulting from a transverse lie. Magnetic
      resonance imaging].

PMID- 12235578
TI  - [A pilot study of methylphenidate and parent training in the treatment of
      children with attention-deficit hiperactivity disorder].
AB  - OBJECTIVE: This study gives information about a parent training program and a
      clinical trial with a stimulant drug (methylphenidate) to reduce the symptoms of
      attention deficit hiperactivity disorder (ADHD) in a group of children in
      Venezuela. PATIENTS AND METHODS: 24 children, aged between 6 and 10 years and
      diagnosed as having ADHD, identified in ADHD screening days, were randomly
      assigned to two groups of treatment: parent training and a stimulant drug
      (methylphenidate). RESULTS: Both groups showed an improvement in their symptoms,
      to different degrees, after treatment. The differences were statistically
      significant, as evaluated by their parents, regarding the symptoms of
      inattention, hyperactivity and impulsivity. The teachers observed a significant
      improvement for the medication group with respect to the symptoms of
      hyperactivity and impulsivity, but no change in the inattention, whilst in the
      parent training group there was only significant difference in the ADHD index.
      There was no difference in the effectiveness of the two types of treatment.
      CONCLUSIONS: When the two programs of treatment were compared it was observed
      that both parent training and psychostimulant medication were effective in
      reducing the symptoms of ADHD. Although there was no difference in the
      effectiveness of the two programs, there was a tendency for medication to be more
      effective

PMID- 12235579
TI  - [Juvenile xanthogranuloma of the central nervous system].
AB  - INTRODUCTION: Juvenile xanthogranuloma (JXG) is a benign histiocytosis affecting
      mostly skin, although it may also be extracutaneous. Lesions tend to regress
      spontaneously, but there are cases of bad prognosis. CASE REPORT: We report the
      case of a girl aged 3 months with JXG involving skin and, asymptomatically,
      central nervous system (CNS) and lungs. At age 4 months, the bigger CNS lesion,
      placed in the right cavernous sinus and whose growth might have had important
      neurologic repercussions, was excised. After surgery she presented seizures with
      initial response to antiepileptic drugs. At age 8 and 10 months surgery was again
      necessary for appearance of a tension pseudoyst in postsurgical bed; a
      cystoperitoneal shunt was instaured and seizures were controlled. When the
      patient was 12 months old, the diagnosis of hypothyroidism was established, with
      a favourable response to levothyroxine. At present, the patient is 2 years 8
      months and has a slightly slow neurologic development, with occasional short
      seizures. Skin lesion is smaller, lung nodules have regressed and, regarding CNS
      lesions, the bigger has not recurred and the other one remains stable.
      CONCLUSIONS: Some authors propose doing JXG s extension study only when suggested
      by clinical findings, so long as an effective therapy and the advantage to
      presymptomatic treatment are not well established. We wonder whether early
      diagnostic and therapeutic approach to silent deep lesions might lead to a better
      outcome of patients with JXG, particularly those with CNS involvement.

PMID- 12235580
TI  - [Behcet's disease in children: cortical calcifications].
AB  - INTRODUCTION: Between 5 and 48% of the patients with Behcet s disease have
      neurological abnormalities. In children, meningoencephalitis as an initial
      manifestation of the disease is not frequent. CASE REPORT: We present a four
      years old girl with a Behcet s disease. When she was six months of age, during an
      hospitalization caused by malnutrition and respiratory infection, she had
      developed an aseptic meningoencephalitis and laboratory test showed
      hypergammaglobulinemia. When she was 21 months old, she had seizures as
      epilepticus status, and good response was achieve treating with anticonvulsive
      drugs. She did not repeat episodes of epileptic seizures, but the patient showed
      language and neuromotor problems. CT was abnormal with asymmetric ventricular
      dilatation and increased subarachnoides cortical sulci with multiple
      calcifications in those areas. She also suffered respiratory and gastrointestinal
      infections that required hospitalization. At the age of 3 years and 6 months, she
      had occular affection with uveitis, oral and genital ulceration. The clinical
      history of the girl consisting of meningoencephalitis, gastrointestinal and
      respiratory disorders, later presentation of uveitis and oral and genital ulcers
      confirmed the Behcet s disease diagnosis. CONCLUSION: We present a girl with
      multisystemic disorders characteristic of the Behcet s disease. Initially she had
      an aseptic meningoencephalitis developing cortical calcifications.

PMID- 12235581
TI  - [Molecular basis of Huntington's disease and possible pathogenic mechanisms].
AB  - INTRODUCTION: Huntington s disease is one of the, at least, nine neurological
      disorders caused by a CAG triplet expansion coding for a poly glutamine sequence
      in the corresponding protein. Huntington s disease affects 3 7 in 100.000
      individuals in Western Europe descendent population and the symptomatology
      comprises motor (including chorea and rigidity), cognitive (subcortical
      dementia), and psychological (including irritability and depression)
      manifestations until death. DEVELOPMENT: Neuropathology is extremely restricted,
      with atrophy occurring in the striatum and, to a lesser extent, in the cerebral
      cortex. Microscopically, the neuropathology is characterized by neuronal loss,
      reactive gliosis, and intraneuronal protein aggregates. Since the initial
      description of this disease by George Huntington in 1872, substantial advance has
      been achieved in the understanding of this pathology. The pathogenic gene and
      mutation were identified in 1993. This allowed the generation of multiple in
      vitro, cellular, and animal models of Huntington s disease. These studies have
      originated multiple hypotheses regarding the mechanism by which huntingtin with
      an expanded poly glutamine tract exerts its toxicity. CONCLUSION: We try to
      summarize the current knowledge about this disease from the clinical
      manifestations to the molecular basis, in an attempt to offer a global view of
      this pathology.

PMID- 12235582
TI  - [Initial axonal lesion in multiple sclerosis. Reasons for early treatment].
AB  - INTRODUCTION AND METHOD: There is no curative treatment for multiple sclerosis
      (MS) nor are there precise data that enable us to ensure a patient is given an
      accurate prognosis of his or her illness. A small percentage of patients will
      have such a particularly benign course that they will not require preventative
      treatment for the attacks. Unfortunately, many of them, above all those that
      display high lesion loads in the magnetic resonance imaging (MRI), will develop a
      relapsing remitting illness that will leave permanent sequelae. The initial
      inflammatory phases of MS are essential since they establish an accumulation of
      axonal lesion that will mark the future of a possible, more or less serious,
      neurodegenerative phase and which will become manifest in the second progressive
      phase. Until now, useful treatment in MS has acted on the inflammation, and
      efficiency is low in the later stages. For this reason, some authors recommend
      that IFN b 1a IM must be initiated in patients after the first attack, now that
      its use has recently been approved in the European Union in these cases.
      CONCLUSION: We believe that each patient should be informed and treatment
      proposed following the first demyelinating attack, provided he or she meets the
      criteria needed to be considered as having a high risk of developing MS, such as
      having a high lesion load in MRI.

PMID- 12235583
TI  - [Effectiveness and tolerability of the new antiepileptic drugs: the position of
      levetiracetam].
AB  - AIMS: To evaluate the effectiveness and tolerability of levetiracetam in relation
      to other antiepileptics. METHOD: Selecting the first choice antiepileptic for a
      particular patient must be based on solid evidence. Randomised double blind
      clinical trials offer perhaps the most solid evidence of the efficiency and
      tolerability of a medication. Nevertheless, trials that compare new
      antiepileptics in monotherapy are scarce. For this reason, we have performed a
      series of meta analyses that help to evaluate different drugs in a comparative
      manner. Unfortunately, the meta analyses published, although they do provide the
      specialist with valuable information, show limitations that make them difficult
      to interpret. The evidence available suggests that, in spite of there being a
      differentiating tendency between certain medications both in effectiveness and in
      tolerability, the differences between them do not reach statistical significance.
      CONCLUSIONS: Levetiracetam has been shown to be an antiepileptic drug with
      unquestionable advantages: favourable pharmacokinetic properties, rapid
      titration, high efficiency and low toxicity profile. In addition, there is
      preliminary evidence that it has a wide spectrum, that is to say, it is effective
      not only in focal but also in generalised seizures.

PMID- 12235584
TI  - [New discoveries regarding the physiopathology of the cerebellum].
AB  - OBJECTIVES: To report recent advances regarding the physiopathology of the
      cerebellum in childhood. DEVELOPMENT: Many advances have been made in
      understanding the physiopathology of the cerebellum so we have limited ourselves
      to evaluation of the data available on the possible part played by the cerebellum
      in cognitive function. We then give details of the congenital disorders of
      metabolism in which the cerebellum is directly involved, especially neuro imaging
      aspects. It is impossible to give details of each and every cerebellar syndrome
      with neurological clinical features so we describe only four disorders: Joubert s
      syndrome, the Dandy Walker syndrome, carbohydrate deficient glycoprotein syndrome
      and finally pontocerebellar hypoplasia in its two forms of presentation. We
      analyze recent advances in relation to clinical and neuro imaging aspects of
      various cerebellar disorders. CONCLUSIONS: Great advances have been made in
      understanding the cerebellum in childhood. It is important to know about them
      because of their implications, especially in cognitive function.

PMID- 12235585
TI  - [The contribution of the cerebellum to cognitive function in childhood].
AB  - INTRODUCTION: Cerebellum traditionally has been considered as a neural structure
      dedicated to motor control. Published studies in the last decades suggest that
      the cerebellum has an important role in behaviour and cognition specially in
      paediatric age. OBJECTIVE: We review the cerebellum role in cognitive function in
      developmental and acquired cerebellar pathology.

PMID- 12235586
TI  - [Clinical aspects and diagnostic and therapeutic approaches to motor and sensory
      hereditary neuropathies (NHMS)].
AB  - INTRODUCTION: The classifications of peripheral neuropathies are continually
      being revised in the light of advances in genetic and biochemical investigation.
      OBJECTIVE: We establish a classification based on the pathology found in
      different anatomical structures of nerves: the Schwann cell, myelin, axon and the
      different genes involved in causing neuropathies. Diagnosis is based on data from
      the clinical history, physical examination and electromyography and their
      correlation with the type of inheritance in relation to the different genes
      localized to (a) the Schwann cell: periaxin gene (PRX) encoding L and S periaxin.
      Stabilisation of the myelin acting as a signal tranducer. NDRG1 down stream
      regulated gene 1 and 2 acting as transcription factors in embryogenesis.
      EGR2/Krox 20 has an important function in myelinization. (b) Myelin: P0 membrane
      protein zero (MPZ) stabilizes the myelin. P1 myelin basic protein (MBP), is
      analogous to the myelin protein of the central nervous system (CNS) P2 found in
      the cytoplasm. PMP22 (peripheral myelin protein) also stabilizes the protein. MAG
      (myelin associated glycoprotein) has antigenic properties. (c). Axon. A
      foundational mutation (892C Y) in the gene of the lamina (LMNA) of the light
      neurofilaments (NF L). Mutations in the KIF1Bb gene which encodes the protein
      kinesin. We also make an aetiological analysis of some classical syndromes,
      especially the D jerine Sottas syndrome. CONCLUSION: The systematization used,
      based on clinical and electrophysiological data in relation to the different
      genes involved in the various anatomical structures constitutes a logical,
      diagnostic approach which is very useful.

PMID- 12235587
TI  - [Advances in the molecular genetics of the hereditary neuropathies].
AB  - OBJECTIVE: We reviewed current knowledge of the molecular and genetic bases of
      hereditary peripheral neuropathies, with special emphasis on the senso motor
      neuropathies and their different clinical phenotypes. DEVELOPMENT: The peripheral
      neuropathies show great clinical variability and genetic heterogeneity. To date
      12 genes and over 20 genetic loci have been described in relation to Charcot
      Marie Tooth disease and related neuropathies. The commonest form is the type 1A
      Charcot Marie Tooth disease (CMT1A) caused by tandem duplication of a monomer of
      1.5 megabases (Mb) on chromosome 17q11.2. The CMT 1A duplication is found in 70%
      of the patients with CMT 1. The deletion of 1.5 Mb is the most prevalent mutation
      (85%) in hereditary neuropathy with susceptibility to paralysis due to pressure.
      This monomer includes the PMP22 gene which is affected by a genetic dose effect.
      The different proteins encoded by the genes described are well expressed in the
      Schwann cell and in the nerve axon. They have different functions. There are the
      structural proteins of myelin, transcription factors, cytoskeleton components,
      molecular motors of the microtubules, proteins involved in growth and cellular
      differentiation or with presumed enzyme activity. CONCLUSIONS: Diagnosis of
      molecular pathology is important for genetic counselling. The development of new
      treatment for hereditary neuropathies is based on the generation of animal models
      for the different genes and on understanding the role of the proteins involved in
      axon Schwann cell interaction.

PMID- 12235588
TI  - [Neurophysiological evaluation of children with peripheral neuropathy].
AB  - OBJECTIVE: The purpose of this review is to demostrate the value and limitations
      of neurophysiological evaluation of children with peripheral neuropathy.
      DEVELOPMENT: The neurophysiological evaluation (NPE) is an extension of the
      neurologic examination. The NPE has a high diagnostic sensitiviy but lacks
      etiologic specificity. The NPE includes motor and sensory nerve conduction
      velocity studies (NCV), needle EMG, somatosensory evoked potential (SEP) and
      motor evoked potential (MEP). The NCV allows to determine the component of the
      peripheral nerve fiber involved (axon and/or myelin), type of fibers affected
      (motor and/or sensory), the location of the lesion (proximal and/or distal) and
      the pattern of the nerve involvement (segmental or continuos). The EMG allows to
      determine the presence and degree of denervation and reinervation. CONCLUSIONS:
      The combination of NCV, EMG, SEP and MEP allow: 1. To localize a lesion to the
      diferent regions of the peripheral nervous system (preganglionic and/or
      postganglionic segments of dorsal root, ventral root, spinal nerve, plexus and
      peripheral nerves); 2. To determine severity and prognosis; 3. To select
      candidates for reconstructive exploratory surgery; and 4. To determine treatment
      efficacy and/or natural course of the disease

PMID- 12235589
TI  - [Recent aspects of acute and chronic inflammatory polyneuropathies: Guillain
      Barre syndrome and chronic inflammatory demyelinating polyneuropathy].
AB  - INTRODUCTION: In last decade many advances have occurred in knowledge of
      pathogenic, in the different types of clinic expression and in the therapy of
      both acute and chronic polyneuritis. OBJECTIVE: To review the recent advances in
      the childhood expression of these disorders. DEVELOPMENT AND CONCLUSIONS: Into
      the broad term of Guillain-Barre syndrome (GBS) several types are considered:
      demyelinating, motor sensory axonal and motor axonal, and the Miller Fisher
      syndrome (MFS). Diagnostic criteria, clinical and neurophysiological are
      explained. The actual modes of treatment are reviewed, especially immunoglobulins
      and plasmapheresis. The chronic inflammatory demyelinating polyneuropathy (CIDP)
      is a rare disease in childhood but it is necessary think on it when a picture of
      demyelinating polyneuropathy that seems the more frequent Charcot Marie Tooth
      type 1 polyneuropathy, because the treatment of CIDP changes radically the
      prognosis. Last advances of pathogenic, diagnostic criteria and treatment with
      corticosteroids, immunoglobulins and plasmapheresis are reviewed.

PMID- 12235590
TI  - [Neurological complications of non neurological disorders: from protagonism to
      comorbidity].
AB  - INTRODUCTION: The development of scientific advances, constantly opening new
      frontiers of knowledge, leads to increasing complexity and specialization.
      DEVELOPMENT: The conflict between the never ending medical specialization and the
      opposite tendency, which is based mostly on economic grounds, prevents the
      acquisition of new knowledge across different disorders and diseases. Considering
      the brain as a complex adaptative system, it follows that in order to understand
      its pathogenic mechanisms and to design new therapies, the study of the
      interrelation of all parts concerned must be undertaken. Such approach requires
      the use of increasingly complex degrees of knowledge, covering different fields
      and disciplines. A first step might be the study of neurological complications of
      non neurological disorders. The former should leave its principal status in order
      to be studied as a consequence of the latter by disconcerted neurologists. The
      neurological complications of systemic cancer, congenital cardiopathy and
      autoinmune diseases are good examples of the need for a multidisciplinary
      approach to achieve a satisfactory capacity of diagnosis and treatment.

PMID- 12235591
TI  - [Neurological complications in patients with heart disease].
AB  - INTRODUCTION: The brain needs a constant supply of oxygen and nutrients from
      blood. This fact explains its tight dependence on the cardiovascular system as
      well as the after effects of heart disease on the central nervous system.
      OBJECTIVES: This study intends to describe the main conditions in which a
      neurological disorder appears secondarily to  or coincidentally with  heart
      disease. Methods. A bibliographical review of publications of neurological
      disorders related to heart disease is carried out. RESULTS: The main cardiac
      diseases that can induce neurological disorders include: disturbances of the
      cardiac rhythm, congenital heart diseases, and complications of cardiac
      catheterisation and reparative surgery. Likewise, other conditions  congenital or
      acquired  in which neurological and heart disorders coexist must be considered.
      CONCLUSIONS: Medical practice confirms that heart diseases account for different
      neurological conditions that can manifest by a very variable clinical
      expressivity.

PMID- 12235592
TI  - [Neurological complications of systemic cancer and its treatment].
AB  - INTRODUCTION: Therapeutic advances have attained excellent results in the battle
      against systemic cancer. This has meant cure for many and greater survival.
      However, these achievements have led to a dramatic increase in neurological
      complications due to the cancer itself and the surgical treatment on its own or
      combined with chemotherapy and radiotherapy. These complications, which are very
      common in childhood neoplasias, have had much less attention than those of
      adults, although recently excellent reviews have begun to be published.
      OBJECTIVE: In this paper we review the various complications of systemic cancer
      and its treatment in childhood, emphasizing the differences from that of adults.

PMID- 12235593
TI  - [Neurological involvement in rheumatic disorders and vasculitis in childhood].
AB  - INTRODUCTION: The rheumatic disorders and vasculites are inflammatory processes
      affecting connective tissue in different organs. The inflamed cells liberate
      destructive enzymes which harm tissues, producing IgE, IgM, IgG antibodies and
      autoimmune complexes. OBJECTIVE: To review the current classification of these
      conditions and describe the commonest neurological complications in children.
      Infantile systemic lupus erythematosus is the commonest; it affects the dermis,
      joints, blood vessels, heart, kidney and brain. Neurological features: vertigo,
      ataxia, convulsions, chorea and headache are seen in 25% of the patients.
      Juvenile idiopathic arthritis is another inflammatory disorder of unknown origin
      which affects joints, connective tissue and visceras. Neurological involvement is
      seen in 5%, in the form of cerebral vasculitis, cervical myelopathy, trapping and
      compression of peripheral nerves and neuropathy due to arteritis. Sydenham s
      rheumatic chorea, caused by b haemolytic streptococcal A infection, causing a
      pathological auto immune response is the best known and has increased in
      frequency again in recent years. Vasculitis is caused by inflammatory changes in
      the walls of large, medium and small blood vessels. They lead to deposits of auto
      immune antigen antibody complexes in the blood vessel walls. In the commonest
      infantile vasculites neurological complications are uncommon, but not rare, as
      occurs with Kawasaki disease, infantile Wegener s granulomatosis, Schonlein
      Henoch purpura and Behcet's disease. The usual treatment for this group of
      disorders is corticosteroids and immunosuppressive drugs.

PMID- 12235595
TI  - [Lymphocytic hypophysitis without pituitary dysfunction in a perimenopausic
      patient].

PMID- 12235596
TI  - The effect of dynamic versus isometric resistance training on pain and
      functioning among adults with osteoarthritis of the knee.
AB  - OBJECTIVE: To compare 16 weeks of isometric versus dynamic resistance training
      versus a control on knee pain and functioning among patients with knee
      osteoarthritis (OA). DESIGN: Randomized clinical trial. SETTING: Outpatient
      setting. PARTICIPANTS: A total of 102 volunteer subjects with OA of the knee
      randomized to isometric (n=32) and dynamic (n=35) resistance training groups or a
      control (n=35). INTERVENTIONS: Strength exercises for the legs, 3 times weekly
      for 16 weeks. Dynamic group: exercises across a functional range of motion;
      isometric: exercises at discrete joint angles. MAIN OUTCOME MEASURES: The time to
      descend and ascend a flight of 27 stairs and to get down and up off of the floor.
      Knee pain was assessed immediately after each functional task. The Western
      Ontario and McMaster Universities Osteoarthritis Index was used to assess
      perceived pain, stiffness, and functional ability. RESULTS: In the isometric
      group, time to perform all 4 functional tasks decreased (P<.05) by 16% to 23%. In
      the dynamic group, time to descend and ascend stairs decreased by 13% to 17%.
      Both groups decreased knee pain while performing the functional tasks by 28% to
      58%. Other measures of pain and functioning were significantly and favorably
      affected in the training groups. The improvements in the 2 training groups as a
      result of their respective therapies were not significantly different. The
      control group did not change over the duration of the study. CONCLUSION: Dynamic
      or isometric resistance training improves functional ability and reduces knee
      joint pain of patients with knee OA.

PMID- 12235597
TI  - Disability and health care costs in the Medicare population.
AB  - OBJECTIVE: To determine the effect of activity limitations on health care
      expenditures. DESIGN: Cross-sectional. SETTING: National survey. PARTICIPANTS:
      Data from the 1997 Medicare Current Beneficiary Survey (n=9298), a nationally
      representative sample of community-dwelling Medicare beneficiaries who were older
      than 64 years of age. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The
      impact of patient disability on health care costs (inpatient, outpatient, skilled
      nursing facility, home health, medications). Activity limitations were determined
      by patient assessment of restrictions in activities of daily living (ADLs).
      RESULTS: Over 20% (n=6,500,000) of the entire Medicare population had at least 1
      health-related activity limitation. Total median health care costs per year
      (interquartile range [IQR]) increased as the number of these limitation increased
      (0 ADLs: $1934 [IQR, $801-$4761]; 1-2 ADLs: $4540 [IQR, $1744-$12,937]; 3-4 ADLs:
      $7589 [IQR, $2580-$23,149]; 5-6 ADLs: $14,399 [IQR, $5425-$33,014]). After
      adjusting for confounding characteristics including the impact of comorbid
      illnesses, Medicare enrollees incurred higher health care costs as their number
      of activity limitations increased (0 ADLs: cost ratio=1.0; 1-2 ADLs: cost
      ratio=1.4 [95% confidence interval (CI), 1.2-1.6]; 3-4 ADLs: cost ratio=1.6 [95%
      CI, 1.3-2.0]; 5-6 ADLs: cost ratio=2.3 [95% CI, 1.7-3.2]). The cost increases
      were because of an increase in the frequency of all events (eg, hospital
      admissions, outpatient visits) rather than an increase in the intensity or cost
      of those events. In addition, with increasing activity limitations, there was a
      significant increase in the proportional impact of home health costs such that,
      for those with 5 or 6 limitations, home health costs exceeded the cost of
      outpatient visits. CONCLUSIONS: Activity limitation is an independent risk factor
      for increased health care costs and appears to be more than just a proxy for
      chronic illness.

PMID- 12235598
TI  - Vibratory facilitation of strength in fatigued muscle.
AB  - OBJECTIVE: To assess the effects of tendon vibration on isometric torque and
      electromyographic activity of fatigued muscles. DESIGN: Subjects performed a 30
      trial isometric (2-s maximal effort contractions alternating with 6-s rest
      periods) elbow extensor fatigue series. Three additional trials with the same
      work-to-rest ratio were then performed in which the triceps extensor tendon was
      subjected to a 60-Hz, 1-mm vibration during the rest intervals. SETTING: A
      biomechanics research laboratory. PARTICIPANTS: Thirteen healthy women without
      history of upper-extremity injury or neurologic disorder. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Elbow extension torque was measured with a
      load cell. Triceps and biceps brachii muscle activity was measured with surface
      electromyography electrodes. RESULTS: Elbow extension torque increased 10% (2 Nm)
      during the stimulation trials relative to the control trials (P<.05). The
      associated increase in mean peak-to-peak electromyographic amplitude was 47 %
      (103 microV) for the triceps brachii and 38% (33 microV) for the biceps brachii
      (all P<.05). The electromyographic frequency measures failed to reach the.05
      probability level of significance. CONCLUSIONS: Elbow extension torque and
      triceps electromyographic activity were facilitated by tendon vibration of
      fatigued triceps in healthy subjects. This finding supports the use of
      proprioceptive feedback to facilitate voluntary muscle contractions.

PMID- 12235599
TI  - Electromyographic assessment of back muscle weakness and muscle composition:
      reliability and validity issues.
AB  - OBJECTIVE: To assess the reliability and construct validity of various
      electromyographic indices developed to assess back muscle weakness and muscle
      fiber composition. DESIGN: A prospective study with repeated measures performed
      on 3 days along with comparisons of groups presenting different back strength
      and/or back muscle fiber composition. SETTING: A biomechanics laboratory within a
      rehabilitation center. PARTICIPANTS: Forty male volunteers (20 healthy, 20 with
      chronic low back pain) were assessed on 3 different days to assess reliability
      and to make group comparisons. Thirteen healthy women were also assessed once to
      obtain a third group with known lower strength and different back muscle fiber
      composition. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Surface
      electromyography was recorded for 4 pairs of homologous back muscles while the
      subjects performed, on a dynamometer, static trunk extension efforts.
      Electromyographic parameters were computed to assess muscle weakness and muscle
      fiber composition. The reliability of the data collected across the 3 sessions
      and comparisons between groups were determined. RESULTS: Electromyographic
      parameters generally showed good to excellent reliability, but were insensitive
      to differences in back muscle strength and did not appear to be related to muscle
      composition. Some trends were observed in the electromyographic parameters across
      the force levels, but the large interindividual variability impeded statistical
      comparisons. CONCLUSIONS: The assessment of muscle weakness and muscle fiber
      composition through electromyographic analysis does not appear feasible, at least
      on an individual basis, for the muscles of the back.

PMID- 12235600
TI  - Herpes zoster of the head and limbs: electroneuromyographic and clinical findings
      in 158 consecutive cases.
AB  - OBJECTIVES: To quantify electromyographic and neurographic changes and to
      correlate them with the clinical data of outpatients with herpes zoster. DESIGN:
      Prospective case series. SETTING: Outpatient department. PATIENTS: A consecutive,
      unselected series of 158 outpatient cases (88 women, 70 men; mean age, 64y) of
      herpes zoster of the head and limbs. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Blink reflex and electromyography and motor and sensory nerve
      conduction velocities of nerves and muscles corresponding to affected dermatomes.
      RESULTS: Postherpetic neuralgia (PHN), segmental zoster paresis, and
      polyneuropathy were found in 31%, 19%, and 2.5% of cases, respectively. Absence
      or reduction of sensory action potential amplitudes, blink reflex areas, and
      compound muscle action potential amplitudes were found in 60%, 31%, and 18% of
      cases, respectively. Sensory and motor conduction velocities and motor and blink
      reflex latencies were nearly always normal or only slightly slowed.
      Electromyographic signs of abnormal spontaneous activity were found in 36% of the
      cases. Electrophysiologic alterations were correlated among themselves, with age,
      with presence of segmental zoster paresis, and with absence of antiviral therapy.
      The extent of the skin rash (number of dermatomes affected by herpes zoster) was
      the only variable predictive of disappearance or improvement of PHN. CONCLUSIONS:
      Sensory axonal neuropathy, often associated with similar motor involvement, can
      be shown by classical electrophysiologic methods in herpes zoster. The severity
      of damage to motor fibers was related to damage to sensory fibers, but no
      relation was found between peripheral axon damage and PHN. The site of motor
      system damage may be the ventral roots, plexus, or peripheral nerve. The
      probability of complications and the severity of sensory and motor peripheral
      axonal damage were increased in older patients. Appropriate antiviral therapy
      seems to reduce the incidence of segmental zoster paresis and the severity of
      damage to the peripheral fibers. A reduced extent of herpetic rash was the only
      factor to correlate with a good outcome of PHN.

PMID- 12235601
TI  - Interruptions to amputee rehabilitation.
AB  - OBJECTIVES: To determine the frequency of interruptions to inpatient amputee
      rehabilitation, and to identify the causes, risk factors, and consequences of
      these interruptions. DESIGN: Retrospective cohort study. SETTING: Inpatient
      amputee rehabilitation service. PATIENTS: A total of 254 consecutive patients
      admitted within 90 days of amputation. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Patient age, gender, comorbid medical conditions, amputation
      type(s), days from amputation to admission, admission Medical Outcomes Study 36
      Item Short-Form Health Survey (SF-36) score, rehabilitation length of stay (LOS),
      whether a prosthesis was fabricated, discharge destination, discharge Houghton
      Scale score, discharge 2-minute walk test, and discharge SF-36 score. RESULTS:
      Interruptions occurred in 76 patients (30%). Impaired stump healing caused 46
      (18%) interruptions and acute medical illness caused 26 (10%); 4 (2%)
      interruptions were because of other causes. Higher incidence of interruption was
      associated with female gender, peripheral vascular disease, and decreased days
      from amputation to rehabilitation. The majority of patients with interruptions
      (60/76, 79%) returned to complete rehabilitation. Patients with interruptions had
      significantly longer rehabilitation LOS (48.5 vs 37.0d, P<.001), but functional
      outcome measures at rehabilitation discharge were similar between those patients
      who returned to complete rehabilitation after interruption and those patients
      without interruption. CONCLUSIONS: Interruptions to amputee rehabilitation are
      common and result in longer rehabilitation LOS but do not adversely affect
      rehabilitation outcomes in those who are able to return to complete
      rehabilitation. No subgroup of patients with exceptionally high incidence of
      interruption could be identified.

PMID- 12235602
TI  - Measuring shoulder internal rotation range of motion: a comparison of 3
      techniques.
AB  - OBJECTIVE: To compare the reliability of shoulder internal rotation (IR) range of
      motion (ROM) measured using 3 different methods: standard technique, manual
      scapular stabilization technique, and visual inspection technique. DESIGN:
      Prospective study. SETTING: Clinic-based sports medicine center. PARTICIPANTS:
      Convenience sample of 56 unimpaired high-school athlete volunteers.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Shoulder IR ROM was
      measured by using a digital inclinometer with each of the 3 techniques. All
      measurements were performed independently by 2 groups of examiners and repeated
      to determine intra- and interrater reliabilities. RESULTS: IR ROM measurements
      obtained with the scapula stabilized or by visual inspection were significantly
      less than when measured with the standard technique (P=.001). Intrarater
      reliability was good or excellent for all 3 methods (intraclass correlation
      coefficients=.63-.71), was similar for the scapular stabilization and visual
      inspection techniques, and was superior to that previously reported for similar
      measurements. In general, interrater reliability was lower than intrarater
      reliability for all measurements. CONCLUSION: Because the visual inspection and
      scapular stabilized techniques control for accessory scapulothoracic motion,
      these techniques may represent more valid measures of glenohumeral motion than
      the standard technique. Both the visual inspection and scapular stabilized
      techniques exhibited equally acceptable reliability for clinical use. However,
      because the visual inspection technique may be applied by a single examiner, we
      recommend its use to measure shoulder IR ROM in the clinical setting.

PMID- 12235603
TI  - Nonrandomized studies of rehabilitation for traumatic brain injury: can they
      determine effectiveness?
AB  - OBJECTIVE: To examine the feasibility of investigating rehabilitation
      effectiveness for traumatic brain injury (TBI) with a nonrandomized design.
      DESIGN: Observational cohort with confounder control by regression methodology.
      SETTING: Level I trauma center. PARTICIPANTS: Consecutive series of 365
      individuals with TBI discharged to inpatient rehabilitation or home (78% follow
      up). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Glasgow Outcome
      Scale (GOS), Sickness Impact Profile (SIP), Burden Inventory, and Perceived
      Quality of Life (PQOL). The predictors of interest: discharge to comprehensive
      inpatient rehabilitation or home and inpatient rehabilitation length of stay
      (LOS). RESULTS: Discharge to rehabilitation was associated with poorer
      functioning on the GOS (P=.03) and SIP (P=.57), an increase on the Burden
      Inventory (P=.14), and improved PQOL (P=.20). Similar results were found for
      longer lengths of inpatient rehabilitation. CONCLUSIONS: The results appear to be
      because of a confounding effect rather than rehabilitation. The study design
      could not control for confounding that resulted from unmeasured or difficult to
      measure aspects of the clinical decisions for discharge placement and
      rehabilitation LOS. Furthermore, typical severity indices were inadequate to
      control for injury severity and recovery. Matching designs that investigate TBI
      rehabilitation are also at risk for inadequate confounder control.

PMID- 12235604
TI  - Self-assessed secondary difficulties among paralytic poliomyelitis and spinal
      cord injury survivors in Japan.
AB  - OBJECTIVE: To determine the time course of secondary worsening of difficulties
      (SWD) experienced by postpolio and spinal cord injury (SCI) subjects in the
      general population. DESIGN: Self-report survey. SETTING: Multicenter study in
      general community in Japan. PARTICIPANTS: A total of 662 postpolio and 736 SCI
      subjects who had had contact with some rehabilitation facility. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Respondents completed a questionnaire
      about demographic factors, physical complaints, activities of daily living
      (ADLs), social participation, and a visual analog scale of time course for
      difficulties (VAST-D) devised for the present study in which the subjects drew a
      single curve to indicate the lifetime course of disability as they perceived it.
      RESULTS: Signs of SWD in all extremities of the polio patients and in the upper
      extremities of the SCI subjects were visually shown by the VAST-D. Additionally,
      the prevalence of postpolio syndrome and SWD in the SCI group was estimated to be
      55.3% and 45.1%, respectively. CONCLUSIONS: SWD was visually shown by the VAST-D
      in polio and SCI subjects.

PMID- 12235605
TI  - Racial differences in the incidence of limb loss secondary to peripheral vascular
      disease: a population-based study.
AB  - OBJECTIVE: To evaluate racial differences in limb loss caused by peripheral
      vascular disease in a diverse, statewide population. DESIGN: Retrospective
      analysis of a cohort of dysvascular amputees. SETTING: Maryland State Hospital
      Discharge Data from 1986 to 1997. PARTICIPANTS: Persons with a procedure code for
      lower-limb amputation (ICD9-CM code 84.11-.19) were identified. Patients with
      limb loss because of trauma, malignancy, or congenital anomalies were excluded.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Incidence rates
      standardized for age, gender, and race; and time trends. RESULTS: There were
      27,149 discharges with dysvascular amputations, yielding an average annual rate
      of 44.3 per 100,000 persons. Incidence rates for dysvascular amputations
      increased from 41.4 per 100,000 in 1986 to 47.2 per 100,000 in 1997. For all
      levels of amputation, annual incidence rates among African Americans were
      considerably higher than those of other persons. African Americans were 2 to 4
      times more likely to lose a lower limb than white persons of similar age and
      gender. CONCLUSIONS: Rising rates of lower-limb amputations in the general
      population combined with disproportionately higher rates among African Americans
      are concerning and warrant further investigation into their underlying causes and
      consequences.

PMID- 12235606
TI  - Gait outcomes after acute stroke rehabilitation with supported treadmill
      ambulation training: a randomized controlled pilot study.
AB  - OBJECTIVE: To investigate gait outcomes with supported treadmill ambulation
      training (STAT) associated with regular rehabilitation in acute stroke survivors.
      DESIGN: Randomized controlled trial, pilot study. SETTING: Rehabilitation
      medicine service at a Veterans Affairs medical center. PARTICIPANTS: Seven acute
      stroke survivors assigned to regular intervention group and 6 patients assigned
      to STAT intervention. INTERVENTIONS: Regular intervention consisted of 3 hours
      daily of physical therapy, kinesiotherapy, and occupational therapy. STAT group
      received regular rehabilitation with STAT substituted for usual gait training.
      Participants were tested at baseline, treated for an average of 3 weeks, and
      retested on discharge. The analysis of covariance procedure was used to test for
      differences between the 2 approaches. MAIN OUTCOME MEASURES: Functional
      Ambulation Category Scale, gait speed, walking distance, gait energy expenditure,
      and gait energy cost. RESULTS: The small sample size did not generate enough
      power to detect significant differences in any variable. However, medium to large
      effect sizes of 0.7 and 1.16 standard deviation units were observed for gait
      energy cost and walk distance, respectively. CONCLUSIONS: This pilot study
      indicated that STAT is a safe, feasible, and promising intervention for acute
      stroke survivors. A larger trial is warranted for statistical relevance.

PMID- 12235607
TI  - A new method of using heart rate to represent energy expenditure: the Total Heart
      Beat Index.
AB  - OBJECTIVES: To develop a new method of representing energy expenditure using
      heart rate and to determine its reproducibility compared with the criterion
      standard of oxygen cost. DESIGN: Repeated-measures design. SETTING: University
      gait analysis laboratory and gymnasium at 2 spinal injury units. PARTICIPANTS:
      Twenty unimpaired adults and 17 subjects with spinal cord injury (SCI).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Heart rate and oxygen
      consumption were measured on 20 unimpaired adults walking under controlled steady
      state and nonsteady-state conditions. New methods of estimating energy
      expenditure by using heart rate were compared with oxygen consumption, oxygen
      cost, and Physiological Cost Index (PCI). Nine subjects with SCI, walking with
      and without functional electric stimulation, were assessed to determine use of
      these new measures with this group. Sensitivity to change of the new measurement
      techniques was investigated in 10 subjects with SCI, comparing wheelchair pushing
      to walking. RESULTS: The Total Heart Beat Index (THBI) was developed as a new
      index, calculated by dividing the total heartbeats during activity by distance
      traveled. High repeatability was found under steady-state and nonsteady-state
      conditions (intraclass correlation coefficients,.893-.995). Sensitivity to change
      in activity level was also shown. CONCLUSIONS: The THBI is a simple parameter to
      calculate from continuous heart rate data and provides a reproducible alternative
      to gas analysis and the PCI.

PMID- 12235608
TI  - Hand strength and fatigue in patients with hereditary motor and sensory
      neuropathy (types I and II).
AB  - OBJECTIVES: To compare maximal isometric hand strength and fatigue between
      subjects with hereditary motor and sensory neuropathy (HMSN) and healthy controls
      and to test the reproducibility of handgrip strength (peak force of handgrip
      [PFgrip]) and fatigue. DESIGN: PFgrip and the decline in PFgrip during 3 sets of
      15 contractions were compared. SETTING: University hospital in The Netherlands.
      PARTICIPANTS: Twenty subjects with HMSN and 20 age- and sex-matched healthy
      controls; 15 healthy subjects for the reproducibility part of the study.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: PFgrip and the decline in
      PFgrip were compared by using a digital handgrip dynamometer. Two-point and
      lateral pinch measurements of subjects with HMSN were standardized against
      reference values. Reproducibility measurements were performed on 15 healthy
      subjects on 2 separate occasions within a 1-week interval. RESULTS: PFgrip was
      significantly lower in the HMSN subjects compared with controls (P<.05). Pinch
      measurements also showed a large variance from average normal performance. No
      significant difference was found in the decline in percentage of PFgrip.
      Reproducibility was excellent for PFgrip (intraclass correlation coefficient
      [ICC]=.98; 95% confidence interval [CI],.95-.99) but poor for fatigue (ICC=.62;
      95% CI,.20-.85). CONCLUSION: PFgrip and 2-point and lateral pinch in HMSN
      subjects were significantly reduced compared with healthy controls. Our findings
      indicated that the rate of decline of PFgrip during effort does not vary between
      groups.

PMID- 12235609
TI  - Joint coordination during whole-body lifting in women with low back pain after
      pregnancy.
AB  - OBJECTIVE: To quantify differences in the kinematics of lifting between women
      with low back and/or pelvic pain after pregnancy and women without. DESIGN:
      Comparison study. SETTING: Research laboratory. PARTICIPANTS: Volunteer sample of
      7 women with pain (positive pain drawing, no physical examination) and 9 female
      controls (not matched). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Duration of downward and upward phases, relative instant of box lift-off, joint
      angles, spatial angles of trunk and pelvis, pelvic angle relative to trunk, and
      phase angle relationships between joints. RESULTS: The duration of the upward
      phase +/- standard deviation was longer in the pain group (1731+/-290 ms vs
      1489+/-187 ms, P=.031). At box lift-off, this group had less hip joint flexion
      (101.9 degrees +/-20.8 degrees vs 78.7 degrees +/-12.4 degrees, P=.015) but more
      backward pelvis tilt relative to the trunk, that is, more lumbar spine flexion
      (126.3 degrees +/-16.8 degrees vs 109.0 degrees +/-12.3 degrees, P=.031). The
      pain group showed an immediate transition from lumbar spine flexion to extension,
      whereas the controls maintained peak flexion for about 600 ms. The peak phase lag
      between knee and hip joint extension in the upward phase was larger for the pain
      group (-29.7 degrees +/-8.3 degrees vs -17.2 degrees +/-5.5 degrees, P=.003).
      CONCLUSION: Women with low back and/or pelvic pain after pregnancy showed
      different kinematics of lifting. Further research is needed to determine the
      exact relationship between the altered kinematics and the underlying disorder.

PMID- 12235610
TI  - Reliability characteristics of the Donovan spinal cord injury pain classification
      system.
AB  - OBJECTIVE: To determine the interrater reliability of the Donovan system for
      classification of pain in spinal cord injury (SCI) as well as the clinician-based
      usefulness of each of the classification criteria used in the Donovan system.
      DESIGN: Information pertinent to the Donovan system was provided incrementally by
      videotape for each pain site. After each additional piece of information, the 3
      raters classified the pain site into 1 of 5 types and gave a confidence rating (5
      point Likert scale) regarding the accuracy of their classifications. Thus, each
      pain site was classified 6 separate times, each with an associated confidence
      rating. SETTING: Academic rehabilitation hospital. PARTICIPANTS: Twenty-eight
      persons with traumatic onset SCI reported 60 pain sites. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURE: The short-form McGill Pain Questionnaire.
      RESULTS: Interrater agreement ranged from 50% to 70%. Interrater agreement did
      not change as additional information was provided. In contrast, confidence
      ratings significantly increased as additional information was provided.
      CONCLUSIONS: There was considerable variability between raters using the Donovan
      system for classifying SCI pain. Additional clinical information increased the
      rater's confidence in the accuracy of their ratings but did not improve
      interrater agreement.

PMID- 12235611
TI  - Evaluation of manual wheelchair skills: is objective testing necessary or would
      subjective estimates suffice?
AB  - OBJECTIVE: To test the hypothesis that subjective estimates of the ability to
      perform manual wheelchair skills, by wheelchair users and the therapists working
      with them, accurately reflect the results of objective testing. DESIGN: Within
      subject comparisons. SETTING: Kinesiologic laboratory in a rehabilitation center.
      PARTICIPANTS: Twenty-one wheelchair users and their therapists. INTERVENTIONS:
      The wheelchair users and their therapists subjectively estimated how the
      wheelchair users would perform manual wheelchair skills, followed by an objective
      assessment. MAIN OUTCOME MEASURES: Wheelchair Skills Test (WST, version 2.4), a
      set of 50 standardized skills. RESULTS: The Spearman correlation coefficients
      between the total objective and subjective scores were.95 for the wheelchair
      users and.75 for the therapists. The mean difference between the total objective
      and subjective scores was statistically significant (P=.0002) for the wheelchair
      users (who overestimated their abilities by an average of 17.9%). The percentage
      concordance between subjective and objective scores for individual skills ranged
      from 57.1% to 100% for the wheelchair users and 50% to 100% for the therapists,
      with 25% and 35% of skills, respectively, for which there were no statistically
      significant associations (at a Bonferroni-adjusted alpha level of.001) between
      the objective and subjective scores. The skills that were misestimated by both
      were moving the armrests away, reaching a high object, transferring out of and
      into the wheelchair, folding the wheelchair, incline ascent, negotiation of
      gravel and irregular surfaces, and small curb ascent. CONCLUSION: Although
      subjective ratings by wheelchair users and their therapists provide excellent and
      good estimates respectively of overall manual wheelchair abilities, objective
      testing should be performed when accurate assessments of many specific manual
      wheelchair skills are required.

PMID- 12235612
TI  - The accuracy of clinical assessment of bladder volume.
AB  - OBJECTIVE: To determine the usefulness of physical examination in detecting
      elevated bladder volume. DESIGN: A blinded study of clinical examination by
      physicians to detect elevated bladder volumes compared with a criterion standard
      (ultrasonic bladder volume measurement). SETTING: Outpatient department of a
      general hospital in New Zealand. PARTICIPANTS: Sixteen healthy adult volunteers
      (age range, 21-37 y; body mass index range, 22.9-37.2 kg/m(2)) and 8 qualified
      resident physicians with 2 to 6 years of clinical experience. INTERVENTION:
      Elevated bladder volumes were achieved by randomly allocating the volunteers to
      void or not to void before the clinical examination. MAIN OUTCOME MEASURE:
      Clinical examination of the abdomen by abdominal palpation and suprapubic
      percussion, compared with portable ultrasound findings, to determine whether a
      healthy adult has a full bladder. RESULTS: For bladder volumes of 400 to 600 mL,
      physical examination to detect a full bladder was 81% sensitive (95% confidence
      interval [CI], 54-96), 50% specific (95% CI, 39-68), and 55% accurate (95% CI, 45
      65). The likelihood ratio for a positive finding on physical examination was 1.62
      (95% CI, 1.17-2.24). CONCLUSION: Physical examination of the abdomen by
      relatively junior physicians is unreliable in detecting bladder volumes between
      400 and 600 mL in healthy volunteers.

PMID- 12235614
TI  - Dysphonia associated with epidural steroid injection: a case report.
AB  - A 46-year-old patient with left-side low back pain developed symptoms of
      dysphonia and throat irritation 24 hours after receiving a fluoroscopically
      guided steroid injection into the epidural space. A direct laryngoscopy performed
      before a second injection detected no abnormalities. When dysphonia reappeared 48
      hours after that injection, laryngoscopy revealed edema in the anterior vocal
      cord with thick surrounding mucous. Full clinical resolution of the dysphonia was
      apparent by laryngoscopy 15 days after the second injection. The mechanism of
      dysphonia after epidural steroid injection is unknown, but it may result from a
      systemic steroid effect.

PMID- 12235613
TI  - Systematic review for the early prediction of motor and functional outcome after
      stroke by using motor-evoked potentials.
AB  - OBJECTIVE: To clarify the prognostic value of motor-evoked potentials (MEPs) in
      predicting motor and functional outcomes after acute stroke. DATA SOURCES: A
      computer-aided search to identify original prognostic studies published from 1988
      through 2000; relevant references cited in the retrieved articles were also
      included. STUDY SELECTION: A preliminary screening selected studies in which
      transcranial magnetic stimulation was assessed as a prognostic determinant for
      outcome at the level of impairments (motor recovery) and disabilities (functional
      recovery). The studies were then subjected to a critical review according to a
      priori methodologic criteria. DATA EXTRACTION: Data from the studies were used to
      construct contingency tables with MEPs as a prognostic determinant. The
      distribution of cells was statistically assessed with the Fisher exact test. The
      prognostic test properties were expressed as sensitivity and specificity. The
      clinical significance was determined by odds ratios. DATA SYNTHESIS: Of 85
      potentially relevant studies, 20 met the criteria for the preliminary screening;
      after the critical review, 5 studies were included for analysis and discussion.
      CONCLUSIONS: Analysis of the data from the 5 studies indicated obvious evidence
      for the prognostic value of MEPs for both motor and functional recovery. The
      prognostic test properties for subgroups of patients could be established. In
      predicting motor recovery of the upper extremity, the specificity was
      consistently very high for subgroups of patients with paralysis or severe
      paresis; this test property might be used in clinical practice. We discuss the
      prognostic value of MEPs and offer suggestions for further research.

PMID- 12235615
TI  - Deep venous thrombosis as a result of hypotonia secondary to intrathecal baclofen
      therapy: a case report.
AB  - After repair of the catheter of an implanted intrathecal baclofen (ITB) delivery
      system, a 17-year-old man with cerebral palsy developed acute lower-extremity
      hypotonia. Subsequently, he complained of right lower-extremity pain followed by
      swelling in the popliteal fossa. Doppler studies showed a thrombus extending from
      the femoral vein to the popliteal vein with probable extension into the distal
      portion of the leg. Deep vein thrombosis, an uncommon event in children, has not
      been reported previously as a complication of acute hypotonicity and
      immobilization associated with ITB, regardless of age. Clinicians caring for
      children being treated with ITB should be alert to this potential complication so
      that early diagnostic and treatment measures can be provided. In certain
      circumstances, it may be appropriate to consider prophylaxis against thrombosis.

PMID- 12235616
TI  - Upper-extremity deep vein thrombosis associated with peripherally inserted
      central catheters in acute spinal cord injury: a report of 2 cases.
AB  - Catheter-associated upper-extremity deep vein thrombosis (DVT) carries a 12% to
      36% risk of pulmonary embolism (PE). Acute spinal cord injury (SCI) is a
      thrombophilic state resulting from altered fibrinolytic and platelet function and
      abnormal concentrations of clotting factors. Patients with SCI are frequently
      burdened with the classic risk factors of Virchow's triad including stasis,
      hypercoagulability, and intimal trauma. We present 2 patients with acute cervical
      SCI, both with venous thrombosis of the upper extremity associated with
      peripherally inserted central catheters. Both thrombotic events were insidious,
      and 1 patient developed a large PE. A high index of suspicion is necessary to
      make the diagnosis, and prompt aggressive anticoagulation is warranted absent
      contraindications. Little is known about the prevalence of and the morbidity
      associated with upper-extremity DVT in the SCI population. Our experience
      suggests that catheter-related, upper-extremity venous thromboembolism in SCI
      deserves further study.

PMID- 12235617
TI  - A statement of principles: toward improved care of older patients in surgical and
      medical specialties.
AB  - The statement and recommendations in this report resulted from detailed
      discussions between geriatricians and specialists of 10 medical and surgical
      disciplines, including representatives of the American Academy of Physical
      Medicine and Rehabilitation. These physicians and their parent organizations are
      participants in a major project supported by the John A. Hartford Foundation and
      the American Geriatrics Society. The goal of this project is to improve the care
      of older patients. This position statement reviews demographic forces shaping
      contemporary health care, states the objectives of project, and lists 10 specific
      recommendations. The recommendations encompass attitudes, knowledge, medical
      training, clinical service delivery, and advocacy.

PMID- 12235618
TI  - Traumatic brain injury rehabilitation: are there alternatives to randomized
      clinical trials?
AB  - Randomized clinical trials (RCTs) are widely considered to be the gold standard
      of evidence for treatment efficacy, but they have not been widely applied to
      rehabilitation or, more specifically, traumatic brain injury rehabilitation.
      Ethical, scientific, and resource factors may limit the application of RCTs.
      Thus, rigorous observational alternatives to the RCT would be of great value. In
      the article by Powell et al, an attempt to rigorously apply an observational
      design to assess the relative effectiveness of inpatient rehabilitation versus
      home discharge failed to control for important confounding factors. It appears
      nearly impossible to successfully apply observational designs when the factors
      leading to the applications of different treatments are strongly related to the
      patient's perceived prognosis. However, observational designs may be successfully
      applied when regional or temporal variations in care are studied. Moreover, a
      number of developments in measurement, study design, and statistical analysis may
      expand the role of observational studies in answering questions of rehabilitation
      efficacy and effectiveness.

PMID- 12235619
TI  - Geriatrics and physical medicine and rehabilitation: common principles,
      complementary approaches, and 21st century demographics.
AB  - The demographic changes occurring in the United States transcend the capabilities
      of any specific medical specialty to provide optimum care for the elderly. This
      commentary discusses a statement of principles drafted by representatives of the
      American Academy of Physical Medicine and Rehabilitation who collaborated with
      members of 9 other medical and surgical specialties. In this commentary, we argue
      that geriatrics and physical medicine and rehabilitation (PM&R) share common
      principles and complementary approaches. We urge physiatrists and other
      rehabilitation professionals to address the needs of elderly patients and
      recommend that these principles be incorporated into PM&R practice.

PMID- 12235620
TI  - Sleep-disordered breathing.

PMID- 12235621
TI  - Antihypertensive therapy, nifedipine, and autonomic dysreflexia.

PMID- 12235623
TI  - Community-based referrals for electrodiagnostic studies involving possible carpal
      tunnel syndrome.

PMID- 12235625
TI  - High-tech homes mean a brighter future for seniors.

PMID- 12235624
TI  - State veterans homes digging into SNF occupancy rates.

PMID- 12235626
TI  - States harden stance on abuse.

PMID- 12235627
TI  - Promoting an easier swallow.

PMID- 12235628
TI  - Simple truths about staff retention.

PMID- 12235630
TI  - Hospital supply chain vital part of disaster management plan.

PMID- 12235629
TI  - Full body scans: fad or new frontier for hospital radiology?

PMID- 12235631
TI  - Report: HMO enrollment stabilizing, HMO Medicaid continues to grow.

PMID- 12235632
TI  - Hospitals must put cost and benefits in context.

PMID- 12235633
TI  - Curing energy pains: the energy efficiency best practice programme.
AB  - Energy efficiency provides hospitals with opportunities to save costs, help the
      environment and improve the internal environment for staff and patients. The
      Government has set the health sector an energy saving target of 20%, equivalent
      to cuts of 60 m Pounds by 2001 and 1.2 Mt carbon dioxide. These savings can be
      achieved and exceeded, cost-effectively, if good practise is adopted throughout
      the sector. Assistance in meeting the Government's energy target and meeting good
      practice benchmarks is available from the Energy Efficiency Best Practise
      programme through BRECSU.

PMID- 12235634
TI  - Maintenance as a corporate strategy.
AB  - As we move towards the 21st century, those Manufacturing Industries that survive,
      will have changed their "efficiency" focus away from the conventional wisdom of
      "efficient individual tasks", to focus on the "effectiveness of a total
      manufacturing process". This seemingly insignificant change of emphasis, (from
      task to process) must include "the integration of process plant maintenance into
      the production process". Manufacturing companies, which do not include an
      effective plant maintenance strategy into their business strategy, will not
      survive the business environment of the 21st Century.

PMID- 12235635
TI  - Sustainable regulation of construction.
AB  - The seminar examined the role building codes and regulations can have in
      promoting a more sustainable approach to construction, particularly through their
      application to non-industrial building materials. A range of building materials
      such as straw, bamboo, rammed earth, adobe, and cob (a mixture of clay and
      chopped straw) were described and illustrated by slides to show their building
      potential. The current codes have a prime concern to protect the health and
      safety of people from the built environment. They have been developed almost
      exclusively for mainstream industrial materials and methods of construction,
      which makes them difficult to use with alternative, indigenous, or non-industrial
      building materials, even though those materials may be considered more
      sustainable. The argument was put forward that with only one-third of the world
      population living in modern industrial buildings today, it is not sustainable to
      re-house the remaining rapidly expanding population in high technology dwellings.
      Many of the low technology building materials and methods now used by the
      majority of people in the world need only incremental improvement to be equal or
      superior to many of their industrial replacements. Since these can be more
      sustainable methods of building, there needs to be an acceptance of the use of
      alternative materials, particularly in the developing parts of the world, where
      they are being rejected for less sustainable industrial methods. However, many
      codes make it difficult to use non-industrial materials; indeed, many of the
      industrial materials would not meet the demands that must be now met if they were
      now being introduced as new materials. Consequently, there is a need to develop
      codes to facilitate the use of a wider range of materials than in current use,
      and research is needed to assist this development. Sustainable regulation should
      take into account the full range of real impacts that materials and systems have
      in areas such as resource use and depletion, toxicity of the processes that
      produce them, and their potential for re-use and recyclability.

PMID- 12235637
TI  - Demand for health cash plans continues to grow.

PMID- 12235636
TI  - Handwashing saves lives.

PMID- 12235638
TI  - The Society of Operations Engineers is announced.

PMID- 12235639
TI  - Brassica vegetables and prostate cancer risk: a review of the epidemiological
      evidence.
AB  - Epidemiological studies have yielded conflicting results on the associations of
      diet with prostate cancer. We review evidence that Brassica vegetables are
      associated with reduced prostate cancer risk. Brassica vegetables, which include
      broccoli, cabbage, mustard and collard greens, and bok choy, contain
      glucosinolates, the metabolic breakdown products of which are potent modulators
      of xenobiotic-metabolizing enzymes that protect DNA from damage. Twelve published
      studies give some information about Brassica vegetables and prostate cancer risk;
      six of these studies can be clearly interpreted. Of these, three reported
      statistically significant reduced risks (P < 0.05) and one reported a borderline
      significant reduced risk (P = 0.06) with high Brassica vegetable consumption. The
      epidemiological literature provides modest support for the hypothesis that high
      intakes of Brassica vegetables reduce prostate cancer risk.

PMID- 12235640
TI  - Fat and protein intake and subsequent breast cancer risk in postmenopausal women.
AB  - The role of diet in the etiology of breast cancer has been extensively evaluated.
      Case-control studies generally support an association, while cohort studies have
      produced inconsistent results. This study, carried out on the ORDET cohort, is
      the first prospective Italian study to address the relation between diet and
      breast cancer. Female volunteers were recruited from 1987 to 1992 among residents
      of Varese Province, Northern Italy, an area covered by a cancer registry. A
      semiquantitative self-administered food questionnaire was completed by
      participants. After a mean 5.5 yr of follow-up, 56 cases of invasive breast
      cancer were identified among the 3,367 postmenopausal members; 214 controls were
      randomly chosen from the cohort, matched to cases for age, menopausal status at
      recruitment, recruitment center, and recruitment period. The adjusted odds ratios
      for the highest tertile of intake vs. the lowest were 3.47 [95% confidence
      interval (CI) = 1.43-8.44] for total fat, 3.78 (95% CI = 0.95-15.0) for animal
      protein, and 0.42 (95% CI = 0.18-0.95) for total carbohydrates. These findings
      indicate a significant positive association between total fat and animal protein
      and risk of breast cancer and an inverse association with carbohydrates and
      constitute new evidence for a role of diet in the etiology of breast cancer.

PMID- 12235641
TI  - Dietary vitamin E affects neutrophil distribution and genetic instability in
      murine Mutatect tumors.
AB  - Vitamin E is best known for its ability to scavenge reactive oxygen and nitrogen
      species. Solid tumors are frequently infiltrated with leukocytes, a potential
      source of these reactive species. The Mutatect tumor model is a fibrosarcoma that
      can be grown subcutaneously in syngeneic C57BL/6 mice. We previously showed that
      these tumors are infiltrated with neutrophils and that the number of neutrophils
      correlates with the number of hypoxanthine phosphoribosyl transferase (hprt)
      mutations and loss of an interleukin-8 (IL-8) transgene. Neutrophils are a source
      of nitric oxide, and tumors contain nitrotyrosine, a marker of damage by nitric
      oxide-related species. We also showed previously that dietary vitamin E
      supplements markedly lower the frequency of hprt mutants and the level of
      myeloperoxidase (a neutrophil marker) in a tumor fraction containing "loosely
      bound" cells. In the present report, we examine the effect of dietary vitamin E
      in greater detail. No effect on inducible nitric oxide synthase expression or
      nitrotyrosine levels was observed. However, dietary vitamin E induced a major
      redistribution of neutrophils from the loosely bound cellular fraction to the
      "stromal" fraction, while the total number of neutrophils in tumors was
      essentially unchanged. The loss of the IL-8 transgene seen earlier in Mutatect
      tumors was largely prevented. Vitamin E also prevented the large increase in hprt
      mutants (in the cellular and stromal fractions). Thus vitamin E appears to be
      protective against genotoxicity by scavenging reactive species, but also its
      ability to affect the distribution of neutrophils within tumors may be important.

PMID- 12235642
TI  - Role of testosterone, estradiol, and insulin in diet- and exercise-induced
      reductions in serum-stimulated prostate cancer cell growth in vitro.
AB  - Prostate cancer risk is associated with a high-fat diet and a sedentary
      lifestyle. Placing men on a low-fat diet-and-exercise intervention reduces serum
      hormones, including estradiol, insulin, and free testosterone, that may play a
      role in prostate cancer growth. Eight men participated in a low-fat diet-and
      exercise program for a mean of 14.2 yr, and LNCaP cell growth in culture was
      measured in medium supplemented with 10% of each subject's serum as well as with
      testosterone, estradiol, and insulin added singly or in combination. These
      results were compared in the fetal bovine serum (FBS)-stimulated growth and cell
      growth in serum obtained from a control group of 14 overweight men. In separate
      tissue culture experiments, LNCaP and PC-3 cell growth was also measured in
      response to the addition of testosterone, estradiol, or insulin to steroid
      stripped FBS. LNCaP cell growth in medium with subject serum was 40% less than in
      FBS-stimulated medium and 49% less than in medium with serum from control,
      overweight men. Addition of testosterone, estradiol, and insulin to serum from
      diet-and-exercise subjects significantly stimulated LNCaP cell growth in vitro
      but accounted for only about half of the difference between the control and diet
      and-exercise subjects. Thus other serum changes must also account for the
      significant reduction in LNCaP cell growth observed using medium with serum from
      the diet-and-exercise subjects in the cell culture assay.

PMID- 12235643
TI  - Effect of dietary intake of vitamin A or E on the level of DNA damage,
      chromosomal aberrations, and micronuclei induced in freshly isolated rat
      hepatocytes by different carcinogens.
AB  - Hepatocytes freshly isolated from male Wistar rats fed a common diet or a vitamin
      A- or vitamin E-supplemented diet (each for 21, 28, or 41 days) were assayed for
      sensitivity to DNA breakage and cytogenetic changes induced by carcinogens.
      Different indirectly acting carcinogens were assayed. N-nitrosomorpholine (NMOR)
      was the only agent that induced DNA breaks, chromosomal aberrations, and
      micronuclei in all experiments. Benzo[a]pyrene (B[a]p) and dimethyldibenzo
      [c,g]carbazole (diMeDBC) induced only DNA breaks in all experiments.
      Occasionally, B[a]P induced chromosomal aberrations and micronuclei, and diMeDBC
      induced micronuclei, but not chromosomal aberrations. These results demonstrated
      that the tested carcinogens assayed at concentrations highly effective in a
      hypoxanthine phosphoribosyltransferase/V79 system significantly increased DNA
      damage, while cytogenetic changes were less frequent. In hepatocytes from rats
      fed vitamin A, a reduction in the severity of all three end points was observed
      after NMOR treatment. After B[a]P treatment, we found a reduction in DNA breaks
      and chromosomal aberrations; after treatment with diMeDBC, we observed a
      reduction in DNA breaks. Treatment with vitamin E was less effective: it reduced
      DNA strand breaks induced by B[a]P and partially reduced those induced by diMeDBC
      and NMOR and the level of micronuclei induced by NMOR and B[a]P. Both vitamins
      reduced the level of DNA strand breaks induced by the oxidative effect of a
      visible light-excited photosensitizer.

PMID- 12235644
TI  - Effects of n-6 and n-3 polyunsaturated fatty acids on gap junctional
      intercellular communication during spontaneous differentiation of the human colon
      adenocarcinoma cell line Caco-2.
AB  - Gap junctional intercellular communication (GJIC), which modulates cell growth
      and differentiation, may play an important role in tumor growth. Cancer cells
      have dysfunctional GJIC, but it is not known whether GJIC is mechanistically
      involved in the carcinogenic and anti-carcinogenic effects of n-6 and n-3
      polyunsaturated fatty acids (PUFAs) on colon tumor cells. Caco-2 cells were used
      as an in vitro model to study the effects of PUFAs on differentiated as well as
      undifferentiated human colon cells. The GJIC capacity of this cell line increased
      during spontaneous differentiation. However, no differential effects between n-6
      and n-3 PUFAs on GJIC were observed. Short-term incubation with linoleic acid
      (18:2n-6), alpha-linolenic acid (18:3n-3), arachidonic acid (AA, 20:4n-6), and
      eicosapentaenoic acid (EPA, 20:5n-3) did not influence GJIC, while long-term
      incubation (> 10 days) with linoleic acid and alpha-linolenic acid inhibited GJIC
      of these colon cells. Long-chain metabolites such as AA and EPA were not formed
      after incubation with linoleic acid and alpha-linolenic acid, thus excluding the
      involvement of prostaglandins in the observed effects. Although the exact
      mechanism of GJIC inhibition is unclear, cytotoxicity probably mediated by lipid
      peroxidation products seems to be related, because incubation with more PUFAs (AA
      and EPA) completely abolished GJIC.

PMID- 12235645
TI  - Effects of soybean extract on morphology and survival of Caco-2, SW620, and HT-29
      cells.
AB  - Soybean consumption may be beneficial to prevention of certain human cancers. Low
      incidence of colon cancer in Asian countries is associated with consumption of
      soybean products. A limited number of human and animal studies suggested that
      soybean consumption might prevent colon cancer; other studies did not support
      this conclusion. Therefore, it is important to understand the biological effects
      of soybeans on colon cells. In the present study, cultures of Caco-2, SW620, and
      HT-29 cells were treated with soybean extract, the soluble fraction of a soybean
      product. The crude extract contains proteins and many soluble components of
      soybeans. After incubation with soybean extract (1-6%, vol/vol) for 24 h, most
      Caco-2 cells were found to contain numerous vacuoles within the cytoplasm and to
      become very flat. Exposure to > 6% soybean extract resulted in cell death and
      giant vacuoles. Soybean extract (0.25-2%) induced small vacuoles within the
      cytoplasm of SW620 cells. SW620 cells detached from culture dishes at > 2%
      soybean extract. Exposure to 0.5-2% soybean extract produced vacuoles within HT
      29 cells similar to those observed in SW620 cells. Soybean extract significantly
      reduced density of Caco-2, SW620, and HT-29 cells. Reducing protein content of
      soybean extract reduced but did not abolish its effects on colon cells. Purified
      genistein (12.5 micrograms/ml) was capable of producing morphological changes
      similar to those observed after treatment of colon cells with soybean extract.
      Assays using annexin V-propidium iodide demonstrated that treatment of Caco-2 and
      SW620 cells with soybean extract increased cell death. Membranes of vacuoles in
      soybean-treated Caco-2 and SW620 cells were labeled with Texas red-conjugated
      wheat germ agglutinin, a cytological marker for the Golgi apparatus. Exposure to
      soybean extract enhanced protein levels of Rab6, a small GTP-binding protein that
      is involved in regulation of membrane traffic of the Golgi apparatus. Data from
      this study suggest that exposure to soybean extract or isoflavones affects
      morphology and survival of colon cancer cells and that the response to soybean
      extract varies depending on the cell lines examined.

PMID- 12235646
TI  - Dietary factors and the risk of lung cancer in New Caledonia (South Pacific).
AB  - Our objective was to study the relations between the risk of lung cancer and
      dietary factors in New Caledonia, in the South Pacific. A population-based case
      control study of respiratory cancers was conducted between 1993 and 1995 in New
      Caledonia; we analyzed data for 134 incident lung cancer cases (109 men and 25
      women) and 295 controls (227 men and 68 women) who had completed a food frequency
      questionnaire. Odds ratios (ORs) associated with food and nutrient intakes were
      calculated with unconditional logistic regression, with adjustment for smoking,
      age, and ethnicity. Analyses were performed separately for men and women. Among
      men, no significant associations were observed with any foods, including
      vegetables and fruits. Nonetheless, high consumption of dark green leafy
      vegetables (highest vs. lowest tertile of intake) was associated with decreased
      risk (OR = 0.5, 95% confidence interval = 0.2-1.2, P for trend = 0.12),
      particularly among Melanesians (OR = 0.4, 95% confidence interval = 0.1-1.0, P
      for trend = 0.07). A similar protective effect was also suggested for high
      consumption of poultry (P for trend = 0.06) and fresh fish (P for trend = 0.08).
      No significant association was found with nutrients. Among women, the analyses
      concerned few subjects and were not informative. This study suggests that high
      consumption of dark green leafy vegetables may reduce the risk of lung cancer
      among men in this population.

PMID- 12235647
TI  - Dietary factors in relation to endometrial cancer: a nationwide case-control
      study in Sweden.
AB  - The incidence of endometrial cancer varies up to 10-fold between high- and low
      incidence regions, suggesting the importance of environmental factors, including
      diet, in the etiology of this disease. However, few studies have examined the
      role of diet in the etiology of endometrial cancer. Using unconditional logistic
      regression to estimate odds ratios (OR) and 95% confidence intervals (CI), we
      analyzed data from a large, case-control study of Swedish-born postmenopausal
      women aged 50-74 yr (709 cases and 2,887 controls) residing in Sweden between
      1994 and 1995. We found no clear association between foods or food groups and
      endometrial cancer risk, although high consumption of certain foods, such as
      Brassica vegetables, coffee, and legumes, might be associated with small-to
      moderate reduced risks of endometrial cancer, while red meat consumption might be
      associated with a small-to-moderate increased risk. Daily use of calcium
      supplements appeared to lower endometrial cancer risk (OR = 0.5, 95% CI = 0.3
      0.9, P for trend = 0.04), especially among women with low calcium intake from
      dairy products. On the other hand, the use of iron supplements appeared to
      increase the risk (OR = 1.7, 95% CI = 0.9-3.3, P for trend = 0.03). The findings
      are discussed with respect to previous studies and the possible underlying
      mechanisms.

PMID- 12235648
TI  - Nutrient intakes and adenocarcinoma of the esophagus and distal stomach.
AB  - We studied the relationship between nutrient intakes and adenocarcinoma of the
      esophagus and distal stomach among 124 esophageal adenocarcinoma cases, 124
      distal stomach cancer cases, and 449 controls in a population-based case-control
      study in eastern Nebraska. The residual method was used to adjust nutrient intake
      quartiles or tertiles for energy intake. We observed significant inverse
      associations with risk of esophageal adenocarcinoma for dietary intakes of total
      vitamin A [highest vs. lowest quartile, multivariate odds ratio (OR) = 0.5, P for
      trend = 0.05], beta-cryptoxanthin (OR = 0.5, P = 0.05), riboflavin (OR = 0.5, P =
      0.01), folate (OR = 0.5, P = 0.03), zinc (OR = 0.5, P = 0.05), dietary fiber (OR
      = 0.5, P = 0.05), protein (OR = 0.5, P = 0.02), and carbohydrate (OR = 0.4, P =
      0.02). For distal stomach cancer, only vitamin C (OR = 0.6, P = 0.04), dietary
      fiber (OR = 0.4, P = 0.007), and carbohydrate (OR = 0.4, P = 0.004) were
      inversely associated with risk. Our analyses showed significant interaction
      between dietary fat intake, but not intakes of other nutrients, and respondent
      type for both cancer sites. Subgroup analyses among self-respondents revealed
      positive associations between saturated fat intake and risk of esophageal
      adenocarcinoma (OR = 1.0, 4.1, and 4.6 for intake tertiles, P for trend = 0.02)
      and risk of distal stomach cancer (OR = 1.0, 1.2, and 3.6, P = 0.03). However, no
      such associations were found among proxy respondents. Our data suggest that
      greater intake of dietary fiber, certain carotenoids, and vitamins may decrease
      the risk of esophageal adenocarcinoma, whereas greater intake of saturated fat
      may increase the risk of esophageal adenocarcinoma and distal stomach cancer.

PMID- 12235649
TI  - Impact of losses to follow-up on diet/alcohol and lung cancer analyses in the New
      York State Cohort.
AB  - The main objective of the study was to evaluate whether passive surveillance
      methods can be used in cohort studies without a significant distortion of risk
      estimates when the active follow-up of every participant is not possible. A
      nested case-control study including 525 lung cancer cases and 525 controls was
      conducted among participants of the New York State Cohort Study (n = 57,968 men
      and women), which allowed the active follow-up of a sample of the cohort and the
      assessment of the effect of losses to follow-up. Although there were some
      differences with respect to dietary intake between controls lost to follow-up and
      those located, the results of the nested case-control study including and
      excluding losses to follow-up were comparable. Moreover, the results derived from
      the passive and the active follow-up data were similar. Our findings lent
      credence to passive follow-up methods and suggested that losses to follow-up did
      not compromise the validity of the study. Although attempts to trace every
      participant are preferable in a cohort study, passive surveillance may yield
      unbiased risk estimates when a rare disease is being investigated.

PMID- 12235650
TI  - A randomized study of nutritional support in patients with colorectal and gastric
      cancer.
AB  - Involuntary weight loss is often seen among patients with gastrointestinal (GI)
      cancer. Weight loss may influence quality of life (QoL) and is a predictor of
      survival. The present study is an attempt to improve body weight development in
      GI cancer patients by individual support (IS), including nutritional measures.
      Patients were randomized in a 2 x 2 design between 1) IS, including nutritional
      support, 2) group rehabilitation (GR), 3) IS + GR (ISGR), or 4) standard care
      (SC). Data concerning dietary intake (24-h recalls), body weight, and QoL (EORTC
      QLQ C-30) were collected over 2 yr for 67 patients with colorectal or gastric
      cancer, randomized to IS or ISGR. Data on weight and QoL were collected for 70
      patients with the same diagnoses randomized to GR or SC. Despite a tendency to
      greater weight loss at inclusion, the IS + ISGR group managed to gain weight
      significantly more rapidly and to a greater extent than the GR + SC group. The
      differences became statistically significant at 12 and 24 mo (P < 0.05). Patients
      with weight loss at baseline increased their energy intake and weight more than
      those without weight loss. No differences were seen in QoL ratings between
      randomization groups, but there was a positive correlation between weight
      development and QoL and a negative correlation between fatigue and weight
      development. There was a numerical difference, not statistically significant (P =
      0.3), indicating a shorter time of survival in patients in the GR + SC group. IS,
      including nutritional support, leads to more rapid weight gain than SC in
      patients with newly diagnosed GI cancer.

PMID- 12235651
TI  - Clearance of ascorbic acid in plasma in patients before major maxillofacial
      surgery compared with that in volunteers.
AB  - Reduced concentration of ascorbic acid (AA) in plasma is often observed in tumor
      patients. Besides malnutrition, an increased AA consumption in tumor patients is
      discussed as a main reason for reduced AA concentration in plasma. A reduced AA
      concentration caused by malnutrition would not influence the total clearance
      (Cltot) of AA in plasma; however, a change in AA consumption would alter the
      Cltot. To investigate this further, a study was carried out on 20 patients
      hospitalized for major maxillofacial surgery and 20 volunteers. The Cltot of AA
      in plasma after bolus injection of AA (4 mg/kg body wt) in tumor patients was
      compared with that in volunteers. AA concentration in plasma (P < 0.05) was
      significantly lower in tumor patients (median and 25th and 75th percentiles:
      23.7, 14.6, and 32.7 mumol/l) than in volunteers (median and 25th and 75th
      percentiles: 66.5, 59.6, and 78.6 mumol/l). No significant change in Cltot was
      observed for tumor patients (median and 25th and 75th percentiles: 11.5, 8.0, and
      14.0 l/h) compared with volunteers (median and 25th and 75th percentiles: 11.3,
      9.9, and 13.2 l/h). No indication of an increased consumption of AA in tumor
      patients could be detected. The lowered concentration of AA in plasma observed in
      our patients might be the result of a reduced AA intake.

PMID- 12235652
TI  - Genotoxicity of fecal water in a free-living Irish population.
AB  - The alkaline single-cell gel electrophoresis (comet) assay was used to
      investigate the genotoxicity of fecal water (FW) isolated from 47 Irish subjects
      using Caco-2 colonocytes as target cells. Two methods of comet assay analysis
      were compared to determine the extent of DNA damage and to categorize the samples
      as having no, low-to-moderate, or high genotoxicity. FW was isolated from stool
      samples by centrifugation and tested for its ability to induce DNA damage in Caco
      2 cells. DNA damage was assessed using the comet assay by measuring the extent of
      DNA migration from the nucleus (microns, tail length) or by classifying the
      nuclei into five different categories depending on their morphology. Data
      collected from the two methods were used to categorize the FW samples on the
      basis of their genotoxic activity. Both methods showed good agreement. There was
      an approximately 50:50 split, with half the samples having some level of
      genotoxic activity and half having no genotoxicity. About one-third of the
      samples were considered to be highly genotoxic. There was a trend for low pH of
      the FW to be associated with increased DNA damage, but this was not significant.
      The results presented in this report show a relatively high incidence of
      genotoxic FW in samples derived from a free-living Irish population. Our data
      demonstrate the suitability of classifying nuclei on the basis of their
      morphology as a means of determining DNA damage. This procedure is very rapid
      and, therefore, advantageous in analyzing a large number of slides in the absence
      of an image analysis system.

PMID- 12235653
TI  - Effect of vegetables, tea, and soy on endogenous N-nitrosation, fecal ammonia,
      and fecal water genotoxicity during a high red meat diet in humans.
AB  - Red meat increases colonic N-nitrosation, and this may explain the positive
      epidemiological relationship between red meat intake and colorectal cancer risk.
      Vegetables, tea, and soy have been shown to block N-nitroso compound (NOC)
      formation and are associated with protection against colorectal cancer. To
      determine whether these supplements affect fecal NOC excretion during consumption
      of a high red meat (420 g/day) diet, 11 male volunteers were studied over a
      randomized series of 15-day dietary periods. Seven of these subjects completed a
      further dietary period to test the effects of soy (100 g/day). Soy significantly
      suppressed fecal apparent total NOC (ATNC) concentration (P = 0.02), but
      supplements of vegetables (400 g/day as 134 g broccoli, 134 g brussels sprouts,
      and 134 g petits pois) and tea extract (3 g/day) did not affect mean levels of
      fecal ATNC, nitrogen and ammonia excretion, and fecal water genotoxicity.
      However, fecal weight was increased (P < 0.001) and associated with reduced
      transit time (r = 0.594, P < 0.0001), so that contact between ATNC, nitrite, and
      ammonia and the large bowel mucosa would have been reduced. Longer transit times
      were associated with elevated fecal ATNC concentrations (r = 0.42, P = 0.002).
      Fecal nitrite was significantly suppressed during the tea supplement compared
      with the meat-only (P = 0.0028) and meat + vegetables diets (P = 0.005 for
      microgram NO2/g).

PMID- 12235654
TI  - Adolescent vitamin A intake alters susceptibility to mammary carcinogenesis in
      the Sprague-Dawley rat.
AB  - We tested the hypothesis that adolescent dietary vitamin A intake impacts mammary
      gland development and subsequent sensitivity to carcinogenesis. Sprague-Dawley
      rats were fed a purified diet that was vitamin A deficient, adequate (2.2 mg
      retinyl palmitate/kg diet), or supranutritional (16 mg retinyl palmitate/kg diet)
      from 21 to 63 days of age, the period of adolescent mammary gland development. At
      73 days of age, rats were given 1-methyl-1-nitrosourea (25 mg/kg body wt i.p.)
      and monitored for mammary tumors. Tumors appeared earlier and more frequently in
      rats fed vitamin A-deficient or -supplemented diets. Vitamin A deficiency during
      adolescence was associated with alveolar mammary gland development and precocious
      milk protein expression, while supplementation was associated with ductal gland
      development and suppression of milk protein expression. Differences in
      circulating estradiol and mammary gland estrogen receptor-alpha, and estrogen
      responsive progesterone receptor mRNA were not observed, suggesting that the
      effects of vitamin A on mammary gland development and carcinogenesis are estrogen
      independent. Mammary expression of another hormone receptor that regulates milk
      protein expression, the glucocorticoid receptor, was also unaffected. These
      results demonstrate that vitamin A intake during adolescence alters mammary gland
      differentiation and indicate that a narrow range of vitamin A intake during
      adolescence protects against carcinogenesis.

PMID- 12235655
TI  - Withania somnifera root extract prevents DMBA-induced squamous cell carcinoma of
      skin in Swiss albino mice.
AB  - The chemopreventive effect of Withania somnifera hydroalcoholic root extract
      (WSRE) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer was
      investigated in Swiss albino mice. The skin lesions were induced by the twice
      weekly topical application of DMBA (100 nmol/ 100 microliters acetone) for 8 wk
      on the shaved back of mice. WSRE was administered at the maximal tolerated dose
      of 400 mg/kg p.o. three times per week on alternate days 1 wk before DMBA and
      continued for 24 wk thereafter. The results of the study revealed a significant
      decrease in incidence and average number of skin lesions in mice compared with
      DMBA alone at the end of Week 24. Biochemical parameters were assessed in the
      lesions of WSRE-treated and untreated control mice. A significant impairment was
      noticed in the levels of reduced glutathione, malondialdehyde, superoxide
      dismutase, catalase, glutathione peroxidase, and glutathione S-transferase in
      skin lesions of DMBA-treated control mice compared with vehicle-treated mice.
      These parameters were returned to near normal by administration of WSRE to DMBA
      treated mice. The above findings were supported by histopathological studies.
      From the present study, it can be inferred that WRSE possesses potential
      chemopreventive activity in this experimental model of cancer. The
      chemopreventive activity may be linked to the antioxidant/free radical-scavenging
      constituents of the extract. The anti-inflammatory and immunomodulatory
      properties of WSRE are also likely to contribute to its chemopreventive action.

PMID- 12235656
TI  - Effects of dietary fat on virus-induced pancreatic carcinogenesis in guinea fowl.
AB  - The present study was performed to assess the effects of diets supplemented with
      low (5%) and high (20%) corn oil on a Pts 56 retrovirus-induced model of
      pancreatic carcinogenesis in guinea fowl. The early microscopic lesions appear
      after 3 mo after virus treatment and progress over time. Eight to 10 mo after
      initiation, up to 100% of virus-inoculated birds develop multiple hyperplastic
      and neoplastic pancreatic lesions of duct/ductular phenotype. Short-term (1-4 mo)
      feeding of low- or high-fat diets, beginning at Month 3, had no significant
      effects on body and pancreatic weight. However, the incidence, multiplicity, and
      areas of the pancreatic tissue occupied by intra- and interlobular aggregates of
      hyperplastic ducts with mucinous metaplasia of the lining cells were
      significantly increased compared with the birds fed the common diet. At the same
      time, development of ductular neoplasms, particularly carcinomas, was retarded
      compared with the common diet-fed controls. Long-term (5-7 mo) fat intake
      resulted in an increase in body weight gain, while absolute pancreatic weights
      remained relatively constant. Furthermore, the high- and low-fat diets caused a
      significant increase in areas of retrovirus-induced pancreatic lesions, as well
      as an increase in multiplicity of ductular neoplasms compared with short-term fat
      feeding. It is concluded that short-term feeding of diets supplemented with 5% or
      20% corn oil delayed the development of the common virus-induced ductular
      neoplasms, particularly carcinomas, and had an enhancing effect on development of
      hyperplastic inter- and intralobular aggregates of ducts. This finding was not
      observed, however, during the long-term feeding period of the study.

PMID- 12235657
TI  - The importance of by-products to the US beef industry.
AB  - The use of by-products as nutrient sources for beef cattle will continue to be
      driven by economics. As landfill prices continue to escalate, more by-product
      will become economically viable as cattle feed. These considerations will be
      counter-balanced by safety concerns. American consumers are becoming increasingly
      concerned with the production aspects of their food. The environmental concerns
      associated with additional landfills will have to be balanced against which by
      products consumers will accept in the production of the beef that they consume.
      These will most assuredly heighten over the coming years.

PMID- 12235658
TI  - Soybean hulls, wheat middlings, and corn gluten feed as supplements for cattle on
      forage-based diets.
AB  - Soybean hulls, wheat midds, and corn gluten feed are viable alternative
      supplements for forage-fed cattle. All three result from the processing of major
      Unites States agricultural crops, so large supplies are available. Their value is
      better for ruminant animals than for monogastrics because they contain digestible
      fiber components. These byproducts are widely available throughout the Unites
      States and will generally be more economical than traditional feed grains or
      commercial feeds when used appropriately as supplements to forage-based diets.
      Knowledge about the composition of base forage must be used in planning
      supplementation strategies because base forages vary in protein and mineral
      content [9]. Soybean hulls alone may be a good selection in situations in which
      forages are adequate or high in protein. In situations where forage is marginal
      or deficient in protein, wheat midds, corn gluten feed, or a mix of soybean hulls
      and corn gluten feed might be most desirable. All three feeds can be variable in
      nutrient composition, so they should be analyzed to ensure a balanced nutrient
      level in diets. Soybean hulls are especially variable in crude protein content
      and should always be analyzed when forages are marginal or deficient in protein.
      Despite the fact that published energy levels are substantially lower, research
      has shown that soybean hulls and wheat midds have a value comparable to corn and
      soybean meal in forage-based diets. Corn gluten feed has also been comparable to
      corn and soybean meal in most reports but is closer in value to its published
      energy levels. In general, results with soybean hulls have been surprisingly good
      and consistent, whereas responses to wheat midds and corn gluten feed
      supplementation have been more variable and sometimes disappointing. Feeding
      rates for soybean hulls can range from low to extremely high depending on forage
      availability and desired performance. Wheat midds should be limited in most
      situations to 50% of the expected dry matter intake because of their rapidly
      digested starch content. Corn gluten feed should be limited to approximately 50%
      of expected dry matter intake because of its high sulfur content. Several
      research groups are currently evaluating self-feeding programs for these
      byproducts, and while the potential for health and production problems exist,
      results have been encouraging in most cases. Self-feeding would reduce the labor
      costs of hand feeding and could provide backgrounders with a program to expand
      cattle numbers on a limited land base.

PMID- 12235659
TI  - Brewing by-products: their use as animal feeds.
AB  - Brewers grains, a by-product of beer production, are often used as a livestock
      feed. Because brewers grains provide protein, fiber, and energy, they can be
      useful in a variety of diets. Protein in brewers grains can meet a significant
      portion of supplemental protein requirements; in addition, they provide fiber and
      needed bulk in the diets of ruminants and horses. Brewers grains and other
      brewers by-products have also been fed to pigs, sheep, and poultry. Currently,
      the primary market for wet brewers grains is as a dairy cattle feed; however,
      some may be fed to beef cattle in feedlots. Brewers grains have historically been
      marketed wet or dry, but wet brewers grains currently make up the majority of the
      marketed product. Brewers grains provide protein, energy, and fiber in livestock
      diets, but product variability can influence their utilization and necessitate a
      testing program to determine nutrient content.

PMID- 12235660
TI  - Recycled poultry bedding as cattle feed.
AB  - Since the 1950s, recycled poultry bedding has been used as an economical
      feedstuff for beef cattle. It has been extensively studied at several experiment
      stations around the world with regard to its safety and nutritional aspects. It
      will continue to be closely scrutinized as the public increases its awareness of
      agricultural issues. As this study was being prepared, the news media was
      "spotlighting" bovine spongiform encephalopathy. Currently, in the United States
      there is a ban on incorporation of mammalian-derived protein feeds into ruminant
      diets. This has led to a requirement of beef cattle producers signing affidavits
      indicating that they had met this obligation. Some poultry companies use ruminant
      meat and bone meal in broiler diets when least-cost formulation indicates that it
      is economically desirable. This then poses the question of whether feeding RPB to
      beef cattle should be permitted if the birds had been fed ruminant meat and bone
      meal. It also raises the question of whether cattle grazing pastures fertilized
      with RPB are exposed to ruminant meat and bone meal. Because of the importance of
      pasture fertilization as a waste disposal solution for the poultry industry, it
      seems that the issue will be quickly resolved by omitting the ruminant meat and
      bone meal from poultry diets should concerns increase. Use of RPB, like many
      byproduct feeds, requires a higher level of management expertise than traditional
      feeds. Despite the potential problems discussed in this study, an informed beef
      cattle producer can gain a financially competitive edge by using RPB. A simple
      processing method, deep-stacking under polyethylene sheeting, can produce a safe
      product that will provide a complete diet when blended with an energy source and
      supplemented with some long-stem fiber. The diets can be used for both brood cows
      and stocker calves for extended periods of time, and the practice of feeding RPB
      is safe for both cattle and consumers [45]. Economic parameters will influence
      the future use of RPB; however, the general public's perception and acceptance
      will ultimately determine its long-term use.

PMID- 12235661
TI  - Feeding cotton products to cattle.
AB  - Despite the potential for gossypol toxicosis (particularly in pre-ruminants) and
      risk factors associated with impaired fertility in bulls, cottonseed products
      offer a safe alternative feed for cattle producers when fed at recommended
      levels. Beef producers seeking to lower production costs should consider using
      cotton byproducts in their feeding programs. If carefully incorporated, cotton
      byproduct feeds can reduce feed costs while maintaining or increasing the level
      of cattle performance. Cottonseed meal will remain a standard protein supplement
      for beef cattle throughout the country. Whole cottonseed has much potential for
      Southern producers near cotton gins if it is purchased in a timely fashion and
      fed according to recommendations. Cotton gin trash, cottonseed hulls, and cotton
      textile mill waste also have potential economic benefits, especially to producers
      located near cotton and cottonseed processing facilities.

PMID- 12235662
TI  - Peanut by-products fed to cattle.
AB  - Peanut by-products supply substantial quantities of feedstuffs to beef cattle
      grown in the same region where peanuts are produced. Included in the list of
      products fed to cattle are peanuts and peanut meal, peanut skins, peanut hulls,
      peanut hay, and silages. Residual peanut hay is by far the most widely used
      peanut by-product fed to beef cattle, and if it is properly harvested with
      minimal leaf shatter, it is comparable to good-quality grass hays in nutrient
      content. Peanut skins are often included in small quantities in cattle and pet
      foods, supplying both protein and energy. High tannin content of peanut skins can
      cause severe performance depressions in beef cattle if peanut skins are included
      at levels higher than 10% of the diet, unless diets contain relatively high CP
      (above 15% CP), or additional N sources are added such as ammonia or urea.
      Because dairy cattle diets are often above 16% CP in the total dietary DM, peanut
      skins may increase milk production when added at levels up to 16% of the dry
      matter. Peanut hulls are effectively used as a roughage source at levels up to
      20% of beef finishing diets, for bedding in dairy cattle loafing sheds (if tested
      and found to contain low aflatoxin levels), and in a variety of manufactured
      products. Peanut hulls are economically priced because of their quantity, their
      inherent high fiber, and low CP content, and they should not be fed as a primary
      feedstuffs for beef cattle. Peanut by-products are generally priced below other
      by-products, and they can be incorporated into a variety of supplements and diets
      for cow herds, growing-finishing cattle, and dairy cattle.

PMID- 12235663
TI  - Citrus pulp for cattle.
AB  - Citrus pulp is classified as an energy concentrate by-product feed. Citrus by
      products fed to beef cattle include citrus molasses, citrus meal, wet citrus
      pulp, dried citrus pulp, and pelleted citrus pulp; however, in current production
      systems, pulp (wet, dry, and pelleted) is the only by-product commonly used.
      Citrus pulp production in the United States is limited to specific subtropical
      regions, of which south central Florida remains the largest with additional
      production in California and Texas.

PMID- 12235664
TI  - Canola and sunflower meal in beef cattle diets.
AB  - It is apparent from the limited research that sunflower meal is a biologically
      and economically useful protein source for growing and finishing cattle.
      Similarly, beef cows can be provided supplemental protein effectively with
      sunflower meal. Sunflower meal may be especially useful in diets where degradable
      protein is required, such as lower quality forage or high corn finishing rations.
      The increased bulk of this relatively high fiber meal may affect logistics, but
      ruminants are positioned to be more tolerant of high fiber levels than other
      species. Additional research is warranted to evaluate practical and economic
      aspects of using sunflower meal in beef cattle diets.

PMID- 12235665
TI  - Potato by-product feeding in the Pacific northwest.
AB  - Potato by-products are an important component of cattle feeding operations
      throughout the Pacific Northwest. In turn, without cattle feeding operations,
      potato processors would have a major disposal problem with potato waste. It is
      estimated that 98% of the cattle throughout the Pacific Northwest are being fed
      potato waste in one form or another. This inexpensive energy source allows cattle
      feeders in the Pacific Northwest to feed cattle at a competitive price compared
      with cattle feeders in the Great Plains region.

PMID- 12235666
TI  - Health and production aspects of feeding sweetpotato to cattle.
AB  - If certain guidelines are followed when feeding sweetpotatoes to livestock it is
      possible to minimize health hazards. Careful herd management and the recognition
      of specific biomarkers such as excessive dental deterioration could aid in the
      early identification of feed problems. Where these tubers are produced locally in
      abundance there can be an economic and environmental incentive to divert waste
      sweetpotato by-products toward livestock feed. The feeding of culled
      sweetpotatoes and processed sweetpotato waste by-products can have three major
      benefits. First, expensive disposal costs are reduced. Second, negative
      environmental impacts from landfill dumping and crop spreading are limited.
      Third, the culled sweetpotatoes and SPCW offer an inexpensive and nutritious
      alternative feed ration for livestock that may increase economic returns.

PMID- 12235667
TI  - [Evaluation of gamma-glutamyltransferase activity and reduced glutathione
      concentration in liver of rats with acute chlorfenvinphos poisoning ].
AB  - The aim of this paper was estimation the GGT activity and GSH concentration in
      the liver of rats intoxicated with chlorfenvinphos. The experiment was conducted
      on male Wistar rats divided into three groups: control--which received oil and
      examined--receiving oil solution of chlorfenvinphos in dose of 0.5 LD50 and 0.1
      LD50. At the 1st, 24th and 48th hour after intoxication an activity of enzyme was
      determined. The GGT activity increased after 48th hour of intoxication with the
      lower dose of insecticide and after 1st, 24th and 48th with higher dose. The GSH
      concentration increased at the 1st, 24th and 48th hour of intoxication with
      chlorfenvinphos at dose 0.1 LD50 and at the 24th hour of intoxication with
      chlorfenvinphos at dose 0.5 LD50. We suppose that increase in the liver GGT
      activity can result from disturbance in hepatic function. This increase can
      influence on the reduced glutathione level.

PMID- 12235668
TI  - [Determination of eight trichothecene mycotoxins using GCMSMS methods. I.
      elaboration of MS/MS conditions].
AB  - Trichothecene mycotoxins are commonly distributed in cereals in the world. Rapid
      and accurate methods for the determination of these toxins are required to
      prevent the intoxication of human and to contribute to the supply of safe foods
      and feed. MSMS mode was applied for identification of eight trichothecene
      mycotoxins with Finnigan/Mat GCQ GC/MS system. We describe here optimal
      parameters of CID and to obtain best pairs of ions (precursor ions and daughter
      ions) for all analysed toxins.

PMID- 12235669
TI  - [Determination of chlorinated hydrocarbons in coffee beans].
AB  - Chlorinated hydrocarbons (gamma-HCH, DDT and their analogous metabolites) were
      determined in coffee beans. Four sorts of green coffee beans and 18 sorts of
      burnt coffee beans were used in the research. The method was based on extraction
      of fat and its destruction with concentrated sulphuric acid. Chlorinated
      hydrocarbons were extracted with n-hexane, separated and quantitatively
      determined by gas chromatography. The presence of chlorinated hydrocarbons was
      detected in green coffee beans and, in smaller quantities, in burnt coffee beans.
      The concentration of chlorinated hydrocarbons was lower in medium and darkly
      burnt coffee beans than lightly burnt coffee. The level of DDT and its
      metabolites in final product decreased after coffee burning at higher
      temperatures. After brewing the grind coffee beans the remains of chlorinated
      hydrocarbons were detected in coffee-grounds at concentration to those found in
      coffee beans. Drinking of natural coffee does not influence an increase of intake
      the chlorinated hydrocarbons by human beings.

PMID- 12235670
TI  - [Evaluation of qualitative properties of amaranth (Amaranthus)].
AB  - The work contains results of determination of protein, fat, carbohydrates, water,
      ash, energy value, B group vitamins (B1, B2, PP, B6) and minerals (Ca, P, Mg, Fe,
      Na, K, Cu, Mn, Zn, Co, Ni, Cr, Cd, Pb) in three products of amaranth. The
      nutrients components were determined by general approved analytical methods.
      Vitamins group B were determined using microbiological methods. Minerals like Ca,
      Mg, Fe, Na, K, Cu, Mn, Zn, Co, Ni, Cr, Cd and Pb were determined using the flame
      AAS method. Phosphorus was determined spectrophotometrically as phosphates with
      ammonium molybdate. Mean percentage content of protein, fat, caborhydrates, water
      and ash in products of amaranth examined (seeds, meal, expanded seeds "popping")
      were: 13.5-14.4; 7.1-7.6; 63.8-71.7; 3.0-12.3; 3.1-3.4 respectively; there energy
      value expressed in Kcal/100 g were 373-412. Vitamins content in products of
      amaranth (mg/100 g) were: 0.019-0.029 thiamin; 0.100-0.143 riboflavin; 1.02-1.20
      niacinamide and 0.563-0.615 pyridoxin. The levels (mg/100 g) of minerals were as
      follow: 204-223 Ca; 712-792 P; 8.3-9.7 Fe; 200-235 Mg; 2.9-3.1 Zn; 1.03-1.38 Cu;
      3.78-4.54 Mn; 6.30-8.42 Na; 318-337 K; 0.040-0.055 Cr; 0.185-0.292 Ni and 0.045
      0.051 Co. Mean contents of cadmium ranged 5-9 micrograms/100 g and lead 27-35
      micrograms/100 g in examined products of amaranth.

PMID- 12235671
TI  - [Microbiologic evaluation of instant soup concentrates].
AB  - The microbiological condition of instant soup powders purchased in retail network
      has been assessed. The study included 37 instant soups (8 types) manufactured by
      four Polish companies. The microbiological quality of a majority of soup powders
      fulfilled the requirements of the standard. No pathogenic bacteria (Salmonella,
      E. coli and Staphylococcus aureus) were detected, nor were there any spores of
      sulphitereducing anaerobic bacteria found. However, some samples of powders,
      mainly from one manufacturer, did have an excessive total number of bacteria (>
      10(5) cfu/g) and a reduced (down to 0.01 g) level of coliform count. Aerobic
      bacteria occurring in powders were of vegetative and spore forms and exhibited
      the activity of amylo-, lipo- and proteolytic exoenzymes. The quantity of moulds
      did not exceed 100 cfu/g in a majority of samples. They were mainly represented
      by Penicillium sp., Aspergillus sp., Alternaria sp. and Cladosporium sp.

PMID- 12235672
TI  - [Contents of calcium and phosphorus in the diet of youth from Warsaw elementary
      schools].
AB  - The purpose of this study was an assessment average daily intake of calcium and
      phosphorus by prepubertal adolescents (aged 11 and 12) during monitoring their
      diets in last 10 years. In 1989-1999 years, it was investigated 767 randomly
      selected girls and 817 boys, aged 11 and 12 in Warsaw. Information on dietary
      intake was obtained by 24-hour recall method, always spring, having
      representation of weekdays and weekends. Among environmental factors, nutrition,
      and particularly calcium intake is assumed to influence whether the genetically
      determined maximal peak bone mass is reached. However, near half of examined
      prepubertal adolescents have intake less than 600 mg calcium per day. It was also
      observed low calcium to phosphorus ratio in diets and stated Ca:P < 0.25 among
      10% diet in different groups of girls and boys. Consequently, due to consider the
      activity educational efforts directed to prepubertal adolescent with reference to
      means realization of calcium RDA in daily diet through increase milk and dairy
      products consumption.

PMID- 12235673
TI  - [Dietary knowledge and practice in pregnant women].
AB  - The objective of the study was to evaluate the level of knowledge about the
      influence of diet during pregnancy on the development and health of a child,
      among pregnant women in relation to their eating habits. The diet of a woman
      before and during pregnancy has immense influence on the course of pregnancy and
      health of a child--both after its delivery and in the future. Lack of dietary
      knowledge and the knowledge about consequences of malnutrition among future
      mothers may result in a lot of dietary indiscretion, which in turn can cause
      deficiency or excess of energy and particular nutrients, as well as abnormal
      course of pregnancy. Hence, for keeping a proper diet during pregnancy a woman
      must not only know the healthy eating guidelines, but also realise how a diet
      influences the course of pregnancy and child's health. The study was conducted
      with the use of 3 specially prepared questionnaires, among 77 women in the III
      trimester of pregnancy, participating in the Parturition School course. The first
      questionnaire referred to general data (age, education, antropometric data) and
      the way of supplementing diet with medicinal compounds supplying vitamins and
      minerals. The second questionnaire showed the dietary habits before pregnancy,
      while the third questioned the influence of diet on the course of pregnancy and
      health of the infant. In the second stage the eating habits of the subjects were
      studied also with the use of a 24-hour interview and an album of food products
      issued by the Institute of Food and Nutrition. Summing it up, the analysis of the
      results of the study showed that though pregnancy is a difficult period for a
      woman, it did not make the subjects pay particular attention to their diet. The
      study showed also that the majority of women does have knowledge on the influence
      of diet and the influence of her nourishment before pregnancy on the development
      of foetus, however, it hardly results in the change of their eating habits.

PMID- 12235674
TI  - [The sanitary condition of well water in the Pulawy region].
AB  - The objective of the examinations was sanitary hygienic assessment of well water
      within the Nitrogen Plant "Pulawy" area reach compared to the wells located some
      distance off the plant and within the Naleczow resort. The samples were collected
      for five years (1996-2000) and examined for the following physicochemical
      determinations: colour, turbidity, flavour, pH, total hardness, basicity,
      chlorides, iron, manganese, nitrites, nitrates, ammonia, oxidizability and
      bacteriological determinations: bacterium coli and coli faeces as well as total
      count of microorganisms. The examinations showed considerable bacteriological
      contamination and that with nitrate nitrogen, iron, manganese and high turbidity
      of the well water examined. The wells in the N. P. "Pulawy" demonstrated a
      substantially higher level of nitrates, faecal bacteria and their total count.
      Well water is polluted due to uncontrolled activity of the N. P. "Pulawy",
      domestic sewage and industrial wastes, improper location of wells and in some
      cases, their wrong protection.

PMID- 12235675
TI  - [The influence of deionized water on the health status of the population].
AB  - Basing on the literature dealing with the existence of considerable deficits of
      magnesium and calcium in the human organism and on that concerning experimental
      research of the influence of deionized water on animals, it has been shown that
      the deficits of the above-mentioned bioelements may get increased as resulting
      from the oral administration of that water. The purposefulness of continuing
      investigations with the object of recognizing the biological properties of
      deionized water, while being administered to mon for common consumption, could
      have been stated.

PMID- 12235676
TI  - [Tests of the microbiologic barrier in sterile packaging].
AB  - After decontamination, cleaning, maintenance and functional testing, sterilised
      items must be packed suitably. The package must protect sterilised items against
      microbial contamination during removal from the sterilising chamber, and during
      storage or transport until use. The ability of any given pack to withstand
      penetration by bacteria is termed bacterial barrier efficiency. The assurance to
      keep the contents of the packaging sterile is determined by quality of the
      materials and the quality of seals. The research was done to proof the microbial
      barrier, determined by quality of the packaging materials/systems used to
      sterilization in hospital practice in Poland. 4 packaging materials and 4 types
      of containers were tested. In all used methods the growth of microorganisms
      indicated the lack of the bacterial efficiency, the lack of growth--the bacterial
      barrier efficiency. It was proved that two tested specialistic sterilization
      papers, non woven material and specialistic containers (metal with a filter or
      valve, plastic with a filter) are effective microbial barriers because it was no
      microorganisms growth. It has been determined that sulphite bleachery paper of 60
      g/m2 and Schimmelbusch container do not provide the microbial barrier. Based on
      the performed studies it has been determined that sulphite bleachery paper and
      Schimmelbusch container can not be used as sterilization packaging system in
      sterilization practice in hospitals.

PMID- 12235677
TI  - [Hygiene during leisure time among third year students from the Department of
      Nursing and Health Sciences].
AB  - The aim of the study was the assessment of hygiene of leisure time among third
      year students from Faculty of Nursing and Health Science of Lublin Medical
      Academy. It analysed passive and active ways of spending free time. The study
      involved 106 students (55 stationary and 51 extramural) and it was conducted by
      means of questionnaire. The study revealed that students prefer passive types of
      spending their leisure time. The most popular activity was listening to the
      radio, to which they devoted average 2.9 hours a day (listening to music mainly).
      Extramural students listened to the radio shorter than stationary ones (the
      difference was statistically significant). Students spent also a lot of their
      time watching television (average 1.5 hours a day), reading books and newspapers
      (average 1.85 hours a day) and doing housework, which is an active way of rest
      (average 2.7 hours a day), mainly preparing meals and shopping. Students devoted
      the least of their free time to sleep during the day in spite of the fact it is
      an excellent way of rest. The study found also that physical activity was not a
      favourite type of spending free time. Every third student did not do any sport.
      Stationary students did sport 4 times longer than extramural (the difference was
      statistically significant). Only 31% practiced taking a daily walk and only 44%
      of students made tourist trips. 81.9% of them went away during summer holidays,
      but only 31% of them during the winter break. Undoubtedly, the way of spending
      free time by the students under examination was not hygienic as it did not give
      them a sense of relaxation and rest; also the students themselves were not
      satisfied with it.

PMID- 12235678
TI  - An assessment of ethical climate in three healthcare organizations.

PMID- 12235679
TI  - The healthcare organization: new efficiency endeavors and the organization ethics
      program.

PMID- 12235680
TI  - The paradox of paternalism and three steps careproviders can take to help all
      patients.

PMID- 12235681
TI  - Fair distribution and patients who receive more than one organ transplant.

PMID- 12235682
TI  - Case reports from the Harvard Ethics Consortium.

PMID- 12235683
TI  - Carl Schneider's the practice of autonomy: a precis.

PMID- 12235684
TI  - Patient autonomy: imperfect, insufficient, but still quite necessary.

PMID- 12235685
TI  - The alchemy of informed consent.

PMID- 12235686
TI  - Good-bye to all that ... autonomy.

PMID- 12235687
TI  - The practice of autonomy and the practice of bioethics.

PMID- 12235688
TI  - Reluctant patients: autonomy and delegating medical decisions.

PMID- 12235689
TI  - [Activity of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and
      superoxide dismutase (SOD-1) in single brain metastasis].
AB  - The aim of the study was to evaluate the activity of glutathione peroxidase (GSH
      Px), glutathione reductase (GSSG-R) and superoxide dysmutase (SOD-1) in the
      single brain metastases. The activity of the GSH-Px was evaluated with the use of
      spectrophotometry, GSSG-R was evaluated basing on the method of Mize and Langdon
      and SOD-1 with Sykes et al. method. The examinations were carried out in 36
      specimens (10 specimens of healthy brain tissue, 12 specimens of brain
      metastases, 14 specimens of glioma multiforme). The statistical analysis revealed
      significant increase (p < 0.001) of GSH-Px and GSSG-R activity within the single
      brain metastases in comparison with the healthy brain tissue.

PMID- 12235690
TI  - [Serum paraoxonase activity, total antioxidant potential and lipid peroxidation
      products in children with bronchial asthma exacerbation].
AB  - The aim of this study was to investigate serum paraoxonase (PON) activity, total
      antioxidant capacity and serum level of lipid peroxidation products in children
      with exacerbated bronchial asthma. The study was performed in 23 children (17
      males and 6 females, age 3-17 years) admitted to the hospital with asthma
      exacerbation. Aliquots of serum were collected before administration of any
      treatment. Control group comprised of 22 children (11 males, 11 females, age 3-17
      years) admitted to the Department of Orthopedics for planned surgery, none of
      them demonstrated symptoms of asthma or other allergic diseases. Paraoxonase
      activity demonstrated right-skewed distribution both in control and in
      experimental group. The mean PON activity was 15% lower in asthmatic group but
      the difference was not significant. Total antioxidant potential of assayed sera
      as ferric reducing ability was significantly decreased in the group with asthma (
      23.8%) and near-significantly correlated with number of days of hospitalization
      (r = -0.42; p = 0.07). The concentration of thiobarbituric acid-reactive
      substances (TBARS), a marker of lipid peroxidation, was 115.3% higher in
      asthmatic than in control group. TBARS correlated positively with eosinophils
      count in peripheral blood (r = 0.49; p < 0.01) and negatively with antioxidant
      capacity (r = -0.53, p < 0.05). We conclude that serum concentration of lipid
      peroxidation products is increased in children with bronchial asthma
      exacerbation. Total antioxidant capacity of serum is depressed during
      exacerbation of asthma. Serum paraoxonase activity tends to decrease in children
      during exacerbation of bronchial asthma, but the difference is not significant.

PMID- 12235691
TI  - [Usefulness of selected ultrasonographic methods for evaluation of fetal weight
      in twins].
AB  - Evaluation of three mathematical methods, based on ultrasound examination, in
      order to estimate foetal weight in twins and compare them with actual birth
      weight. Retrospective analysis of ultrasonicly assessed 27 pairs of twin babies,
      who were born within 10 day of ultrasound examination and then outcome's
      comparison with newborn weight, measured just after the delivery. The ultrasonic
      measurements were performed to calculate estimated foetal weight using
      mathematical models of Shepard, McCallum and Hadlock. All outcomes were compared
      to birth weight. Statistical analysis, employed in our research, was percentage
      error according to formula: % = (EFW - BW) x 100/EFW (EFW - estimated foetal
      weight, BW - birth weight). The mean foetal weight calculated according to
      Shepard's method was 2605.9 g and 2651.6 g, relatively for the first (I) and
      second (II) twin baby. By using McCallum's method outcomes were as follows: (I) 
      2558.4 g (II) -2655.4 g and for Hadlock's method: (I) -2480.9 g and (II) -2540.3
      g. Actual birth weight came to 2664.1 g for (I) and 2639.6 g for (II). Percentage
      error was found -2.23, using Shepard's method, -4.13, using McCallum's method and
      -7.38, using Hadlock's method, for the first twin-baby. Relatively, for the
      second twin-baby, values were found as follows: 0.45, 0.59, -3.91. Shepard's
      method is the most helpful in prediction of birth weight in twin pregnancy.
      Separate evaluation of each of twin babies can be more significant indicator in
      prognosis of appearance in intrauterine growth retardation (IUGR), comparatively
      to evaluation of weight's discordance between both twin-foetuses.

PMID- 12235693
TI  - [Effect of antibiotic therapy on levels of proinflammatory cytokines: interleukin
      IL-1, IL-6 and tumor necrosis factor TNF-alpha in serum of patients with Lyme
      borreliosis].
AB  - We estimated serum concentrations of cytokines: IL-1, IL-6, TNF-alpha in patients
      with diagnosed Lyme disease treated for 14 days with antibiotics. The detection
      of proinflammatory cytokines was performed by ELISA tests. The examination was
      carried out before and after the treatment. The comparison with control group
      stated statistically significant higher concentration of IL-1, IL-6 and TNF-alpha
      before and after the treatment. Comparing the concentrations of cytokines after
      treatment with control group showed normalization only in a few cases. In the
      majority of cases serum cytokines concentrations remained significantly higher.
      That is why we conclude that 14-day-therapy with antibiotic in patients with Lyme
      disease may not be sufficient.

PMID- 12235694
TI  - [T lymphocyte alpha/beta and gamma/delta in peripheral blood of children with
      acute lymphoblastic leukemia].
AB  - The improvement in acute lymphoblastic leukemia (ALL) children treatment results
      in the need of examining their immune system after therapy. The purpose of the
      research was the immune system evaluation in children with low risk ALL
      diagnosis, during the treatment and twelve months after therapy. The examined
      material included 41 children. A group of 16 patients was examined during the
      above the treatment, immediately after intensive chemotherapy. The other 25
      patients were examined twelve months after the completion of therapy. The
      lymphocyte immune phenotype was examined with FACScan flow cytometer using
      monoclonal antibodies. The study confirmed the intensive chemotherapy
      significantly decreases the number of leukocytes, lymphocytes and their
      subpopulations. The period of 12 months after cessation of the chemotherapy is
      sufficient to recover the immune system function in all examined low risk ALL
      children.

PMID- 12235692
TI  - [Effect of hyperglycemia on glutathione peroxidase and superoxide dismutase
      activity in patients with newly diagnosed carbohydrate metabolism disturbances].
AB  - The aim of our study was to estimate the changes of superoxide dismutase (both
      isoenzymes: SOD-Zn, Cu and SOD-Mn in serum and total activity in erythrocytes)
      and gluthatione peroxidase (in erythrocytes) activities in newly diagnosed
      carbohydrate metabolism disturbances. 80 subjects were divided into two groups:
      the control with normal oral tolerance glucose test (OGTT) (n = 44) and
      investigated group (concentration of fasting glucose over 6.1 mmol/l and/or
      concentration of glucose in second hour of OGTT over 7.8 mmol/l) (n = 36). No
      differences of superoxide dismutase and gluthatione peroxidase activities as well
      as negative correlation between gluthatione peroxidase activity and concentration
      of glucose in second hour of OGTT (R = -0.28; p = 0.032) were observed. Falling
      tendency of gluthatione peroxidase activity in erythrocytes in subjects with
      postprandial hyperglycaemia suggest that this enzyme could be an early marker of
      antioxidant status of carbohydrate metabolism disturbances.

PMID- 12235695
TI  - [Instillagel in prevention of postoperative urinary tract infection--randomized
      trial].
AB  - The progress of operative technique, introduction of new drugs, modernizing of
      medical equipment are the cause of long and complicated operations. For that
      reason, the number of patients, who need the catheterization of the urinary
      bladder is increasing. The use of the vesical catheter over 5 days is the cause
      of the urinary tract infection (bacterial and mycotic), the bacteraemia and the
      extension of the time of recovery. The aim of the study was the estimation of the
      usefulness of the preparation Instillagel used at the time of the urinary bladder
      catheterization in the patients before an operation, in aspect of frequency of
      urinary tract infection. Between January and December 2000, 59 patients were
      selected for the study. The patients were divided into two groups. In the first
      group, the preparation Instillagel was used at the time of the catheterization.
      In the control group 2% Lignocainum hydrochloricum was used at the time of the
      catheterization. The study was prospective and randomized. The usefulness of the
      preparation Insillagel was estimated through the comparison of frequency of the
      urinary tract infection in both groups. The catheterization of the urinary
      bladder was performed according to aseptic principle. The difference between
      number and age of the patients in both groups was not statistically significant
      (p = 0.8538). The time of the keeping of the vesical catheter was similar in both
      groups (p = 0.576635). The urinary tract infection estimated on the basis of
      clinical symptoms and laboratory findings was diagnosed in 13 patients (5
      patients in the first group, and 8 patients in the control group). The frequency
      of urinary tract infection was not statistically significant in both groups.
      CONCLUSIONS: The urinary tract infection is frequent complication in patients
      with catheter in the urinary bladder, before operation. The frequency of urinary
      tract infection was not statistically significant in both groups. The discomfort
      and pain occurred with the same frequency in both groups.

PMID- 12235696
TI  - [Epidemiology of secretory otitis media in children examined at the
      Otolaryngologic Clinic in Wroclaw in 1996-1999].
AB  - The aim of the work was an evaluation of epidemiological factors in otitis media
      with effusion (OME) in children. Material consisted of 191 children treated
      surgically in Wroclaw ENT Clinic. The control group consisted of 95 healthy
      children. The evaluation was based on detailed history of the patients and
      physical ORL examination. The factors taken into considerations were: age, sex,
      birth factors, breast feeding, attending to kindergarten, passive smoking, social
      and environmental factors, incidents of upper respiratory airways and middle ear
      infections before OME being diagnosed. Frequent upper respiratory infections,
      acute and recurrent middle ear infections, staying with other children
      (kindergarten) and passive smoking increase the risk of OME incidence.

PMID- 12235697
TI  - [Therapeutic management of hepatic encephalopathy].
AB  - Therapeutic management in hepatic encephalopathy depends on its etiology as well
      as progression degree. Both in acute and chronic encephalopathy one should tend
      to establish probable causes and try to eliminate them. Cutting down on proteins
      in diet is one of the most important suggestions in chronic hepatic
      encephalopathy. In order to reduce intestinal production of ammonia, non
      absorbable disaccharides (lactulose), antibiotics (neomycin) and sodium benzoate
      are the most commonly used. Branched chain amino acids administered orally or
      parenterally may be useful in improving patient's condition and restoring the
      balance of blood amino acids. The GABA-benzodiazepine receptor theory led to
      application of its antagonists, such as flumazenil, in the management of hepatic
      encephalopathy. However, providing a proper treatment is not easy due to unstable
      and often not very characteristic course of hepatic encephalopathy. What is more,
      clinical trials of some drugs used in the treatment of hepatic encephalopathy do
      not confirm their effectiveness.

PMID- 12235698
TI  - [Level of CA 125 antigen in serum of first trimester normal and miscarried
      pregnancy].
AB  - The ultrasound and titres of serum beta-HCG and progesterone are widely used to
      assess the risk of miscarriage at early stages of pregnancy. Although very
      useful, they are not considered as satisfactorily sensitive tests during the
      first three months of pregnancy. Therefore, their value is limited. Evaluation of
      serum levels of CA 125 antigen has been considered as useful in diagnosis and
      monitoring of some ovarian carcinomas. But there are some studies suggesting its
      predictive value when estimating the risk of miscarriage at early stages of
      pregnancy. The authors prove that women with threatening abortion revealed higher
      values of serum CA 125 antigen than those in control groups. The patients who had
      presented the highest values of the antigen later miscarried.

PMID- 12235699
TI  - [ Mutation of mtDNA and genetic background of hypertrophic cardiomyopathy].
AB  - The operation of the structural and functional units of the myocardial
      contractile apparatus relies on mutual myofilament movement, totally ATP
      dependent. As a consequence, cardiac action is integrally connected with the
      production of high energy ATP molecules, which are mainly synthesised in cellular
      mitochondrial structures. Mitochondrial dysfunction can lead to a reduced level
      of ATP, which is necessary to generate movement in the actino-myosin system. ATP
      insufficiencies may be a result of the genetic mitochondrial material (mtDNA)
      mutation, poorer expression of mitochondrial genes (at the transcription and/or
      translation stage), distorted import of proteins from the cytoplasm to the
      mitochondria or erroneous composition of mitochondrial breathing complexes. It
      has been proved that the efficacy of oxidative phosphorylation (mitochondrial ATP
      synthesis) is reduced with accumulated mutation of mitochondrial and/or nuclear
      DNA. The paper is a review of findings on the mutation of mitochondrial DNA
      discovered in patients with hypertrophy of the cardiac muscle. In many cases
      these changes accompany the mutations of the nuclear genes, but they may also be
      the only change discovered in the patient's genetic material.

PMID- 12235700
TI  - [Selected methods for evaluating the autonomic nervous system].
AB  - Dysfunction of autonomic nervous system, accompanying different diseases of
      central and peripheral nervous system, is manifested by cardiovascular,
      gastrointestinal, genitourinary, thermoregulatory, respiratory and pupillary
      disorders. In the paper the methods of autonomic nervous system evaluation are
      reviewed, in particular the most popular cardiovascular and thermoregulatory
      tests.

PMID- 12235701
TI  - [Molecular basis of the classical type of Ehlers-Danlos syndrome].
AB  - Classical type of Ehlers-Danlos syndrome (EDS) is the most common variant of the
      disease, however, its molecular background is still unknown. The paper presents
      the latest findings concerning this type of EDS. In most cases, mutations in
      genes encoding type V collagen were found. In some cases, the mutations were
      excluded indicating the genetic heterogeneity of the disease.

PMID- 12235702
TI  - [Foreign body in the kidney as a cause of erythruria in a 4-year old girl].
AB  - The case of the 4-year-old girl suffering from erythruria is presented. It was
      caused by the foreign body (needle) in the kidney. Surgical removal of the needle
      was performed.

PMID- 12235703
TI  - [Autoimmune hemolytic anemia with atypical presentation].
AB  - 3-year-old boy was admitted to our clinic because of anaemia, high erythrocyte
      sedimentation rate and hepatosplenomegaly. Clinical symptoms suggested
      myeloproliferative disease. Autoimmune hemolytic anaemia with atypical
      presentation was diagnosed on the basis of laboratory findings.

PMID- 12235704
TI  - [Cystic fibrosis and pregnancy].
AB  - The aim of this paper is to present a case of 25-year-old pregnant woman admitted
      to hospital because of severe cystic fibrosis, unstable diabetes and paranoid
      syndrome. Due to the team consisted of pulmonologist, gynaecologist and
      kinesipathist a healthy baby was born. The condition of the woman after
      childbirth was stable. The presented case is a rare example in literature
      concerning the case of pregnant woman suffering from mucoviscidosis as well as
      the trial of establishing the guidelines of management in these cases.

PMID- 12235705
TI  - [Cause of familial multiple sclerosis].
AB  - The multiple sclerosis was described in 3 persons of a family, in the mother and
      her two adult sons. In the report the necessity of MRI examination was emphasized
      when the neurological signs and symptoms appeared in the family of MS victim. The
      initiation of the immunomodulatory therapy in the early stage of the disease is
      an important step to influence the natural unfavourable course of the disease.

PMID- 12235706
TI  - [The effect of Lvov medical tradition on development of medical sciences in
      postwar Wroclaw].
AB  - In 1945 a group of scientists from Jan Kazimierz University of Lvov came to
      Wroclaw. They undertook a difficult task of rebuilding the local Medical
      University, which was severely destroyed during the World War II, and organizing
      medical studies in postwar Wroclaw. 17 of 26 directors of theoretical chairs and
      clinics which were opened between 1945-50 came from Lvov. In the restored
      institutions they continued researches which they had begun before the outbreak
      of the war in 1939.

PMID- 12235707
TI  - [Treatment of hyperkinetic disorders].

PMID- 12235708
TI  - [Evidence based therapy of children and adolescents with attention
      deficit/hyperactivity hyperkinetic syndrome (ADHS)].
AB  - The article reviews the empirical research on the efficacy of pharmacological and
      psychological treatment of children and adolescents with attention deficit
      hyperactivity disorders (ADHD). The importance of evidence based treatment is
      stressed. Then the results of the internationally most important treatment study
      in this field, the US Multimodal Treatment Study of Children with ADHD (MTA
      Study) are summarized. The study shows the efficacy of both pharmacological
      therapy (mainly stimulant treatment) and behaviour therapy. The combination of
      both interventions was not clearly superior to drug treatment plus counselling
      (medical management). However, Reanalyses show better effects of combined
      treatment. In the German speaking countries the Cologne Multimodal Interventions
      Study (COMIS) was conducted. Some main results of this study are summarised.
      Evidence based conclusions regarding the efficacy of different psychological and
      pharmacological interventions based on meta analyses, review articles and
      empirical studies are summarised.

PMID- 12235709
TI  - [Early prevention of externalizing disorders--basic principles and parent
      centered approaches to prevention of expansive childhood behavior disorders].
AB  - Conduct disorder is an area of mental disorder, in which prevention seems to be
      advisable for different reasons. First, relevant factors that help identifying a
      population at risk are well-known. Second, a number of research efforts showed
      negative developmental trajectories for children with early conduct disorder, and
      third, we have effective treatment programs that facilitate deriving prevention
      strategies. This paper first describes results which clarify the need for
      prevention. Then basic principles and contents of effective prevention programs
      for conduct disorder are described. Finally, four behaviorally oriented examples
      from the numerous existing universal, selected and indicated prevention programs
      are illustrated and discussed.

PMID- 12235710
TI  - [Attention deficit and hyperkinetic syndrome (ADHS) from the psychoanalytic
      viewpoint].
AB  - This paper assumes a psychodynamic background to ADHD, in other words, various
      syndromes many of which are diagnosed as ADHD are caused and maintained by inner
      conflicts. This assumption is based primarily on theories of well-known
      psychoanalysts who started working on symptoms forming the basis of an ADHD
      diagnosis at an early point of research, secondarily on psychoanalytic theories
      which became widely known in recent years. The author emphasizes psychodynamic
      and interactive aspects, whereas the symptoms underlying ADHD are marginalized.
      Furthermore she comments on the latest neurobiological research results, and on
      the one-sided tendency of psychostimulant administration combined or not with
      behavioural therapy and its social function concerning comprehensive the
      interaction between patient, parents and therapists. Finally a more comprehensive
      and integrative approach is proposed.

PMID- 12235711
TI  - [Impulsiveness in children with hyperkinetic syndrome].
AB  - As research on impulsive behaviour in hyperactive children has been rather
      neglected, this study first measured impulsivity using several instruments and
      then compared the outcomes. 31 boys with ADHD participated in this study as well
      as an equal sized male control group (mean age 9;4 years). Each subject completed
      two computerised tests of impulsivity: the Delay of Gratification Test (DGT) as
      well as the Continuous Performance Test (CPT). Additionally, the boy's impulsive
      behaviour was rated by two questionnaires for teachers (the Teacher Report Form,
      TRF, and the Conners Teacher Rating Scale, CTRS). Apart from impulsive behaviour
      the motor activity was measured, as the classification systems ICD-10 and DSM-IV
      differ on the concepts of "impulsivity" and "hyperactivity". The assessment was
      undertaken using a radar-actometer in order to find an association between
      "impulsivity" and "hyperactivity". As expected, there was a significant
      difference between the two groups concerning impulsive behaviour and motor
      activity. As opposed to that result, the correlations of the several instruments
      that measure impulsive behaviour were not constantly significant. The impulsivity
      item on the CTRS is not associated with the CPT and correlates moderate
      significantly with the DGT. These results led to the development of a model that
      includes the construct of "impulsivity" as separate dimension of ADHD.

PMID- 12235712
TI  - [Treatment effects of combined cognitive behavioral therapy with parent training
      in hyperkinetic syndrome].
AB  - In the past cognitive behavioral treatment concepts failed to demonstrate their
      clinical effectiveness in the treatment of ADHD children. We combined a cognitive
      treatment package (CBT) with a special focus on self-instructional and self
      management skills with a subsequent parent management training (PMT) in order to
      reduce academic problems and oppositional/aggressive behavior. 18 children with a
      diagnosis of ADHD combined type and Oppositional Defiant Disorder participated in
      the study. In an A-B study design the effects of a 12 weeks treatment phase (6
      weeks CBT; 6 weeks PMT) were compared with a preceding 4 weeks baseline. Core
      symptoms of ADHD, conduct and homework problems were assessed by weekly
      administration of parent and teacher questionnaires. CBT was effective in
      reducing the core symptoms of ADHD at home, in school and concerning homework
      problems. Moreover conduct problems at home and in school were reduced. PMT
      resulted in a further amelioration of the cited symptoms. We conclude that CBT is
      an important component in the treatment of ADHD provided that aspects of
      generalization are considered. PMT is a useful adjunct to CBT due to its
      effectiveness in situations where children still have problems of self guidance.

PMID- 12235713
TI  - [General practice of pedagogic management by teachers of hyperkinetic attention
      deficit disordered children in the classroom].
AB  - Attention Deficit/Hyperactivity Disorder is one of the most common behavior
      disorders in child and adolescent psychiatry. The problems resulting from the
      core symptoms of the disorder often endure into adolescence and adulthood placing
      these children at significant long-term risk for academic psychological and
      social morbidity. Despite the importance of the school in this process relatively
      few teachers of regular schools have sufficient knowledge about the foundations
      and principles of treatment concerning ADHD nor do they receive adequate training
      how to deal with ADHD related problems in the classroom. Moreover there is a
      significant lack of cooperation between schools, parents and therapeutic
      institutions inhibiting a multimodal treatment. This article resumes the
      experiences of a 3 months ADHD intervention program for teachers in a Cologne
      elementary school. It gives informations and advices for appropriate measurements
      in the classroom setting that include: 1. intensive information of teachers about
      the disorder, 2. intensified involvement of teachers in the treatment process and
      3. the implementation of distinct didactic elements and well structured
      principles of behavior therapy in the school lessons.

PMID- 12235714
TI  - Taurine and taurine-deficiency in the perinatal period.
AB  - Taurine, a non-protein sulfur amino-acid, is the most abundant free amino-acid in
      the body and plays an important role in several essential biological processes.
      Apart from its role in cholesterol degradation, it acts as neurotransmitter, and
      has a function as osmoregulator and antioxidant in most body tissues. During
      pregnancy, taurine accumulates in the maternal tissues, to be released in the
      perinatal period to the fetus via the placenta and to the newborn via the
      maternal milk. It is accumulated especially in the fetal and neonatal brain. Low
      maternal taurine levels result in low fetal taurine levels. Taurine-deficiency in
      the mother leads to growth retardation of the offspring, and to impaired
      perinatal development of the central nervous system and of the endocrine
      pancreas. The adult offspring of taurine-deficient mothers display signs of
      impaired neurological function, impaired glucose tolerance and vascular
      dysfunction; they may develop gestational diabetes and transmit the effects to
      the next generation. This transgeneration effect of taurine-deficiency in the
      perinatal period fits into the concept of fetal origin of adult disease.

PMID- 12235715
TI  - The effect of betamethasone administration to pregnant women on maternal serum
      indicators of infection.
AB  - OBJECTIVE: To study the effect of betamethasone therapy on maternal white blood
      cell count, C-reactive protein and erythrocyte sedimentation rate in women at
      high risk for preterm delivery. STUDY DESIGN: We included women at gestational
      age of 24 to 34 weeks who were treated by betamethasone for enhancement of fetal
      lung maturity, because of imminent preterm labor with intact membranes. Blood
      tests for white blood cell and differential count, C-reactive protein and
      erythrocyte sedimentation rate were drawn before betamethasone injection, 2 hours
      after, and then every 24 hours for three days. RESULTS: 105 women were included.
      The mean white blood cell count increased by 33% on day one, and returned to
      baseline level three days after the first injection of betamethasone. A
      significant rise in neutrophil count, and drop in lymphocyte count was noted as
      early as two hours after the first injection and lasted for two days. Mean C
      reactive protein and erythrocyte sedimentation rate levels were not changed
      significantly by betamethasone treatment. CONCLUSIONS: Antenatal betamethasone
      therapy causes a transient increase in maternal leukocyte count but has no effect
      on serum C-reactive protein and erythrocyte sedimentation rate. This information
      is relevant for preterm pregnant women who are at high risk for chorioamnionitis.

PMID- 12235716
TI  - Chorioamnionitis: elevated interleukin-6 and interleukin-8 concentrations in the
      lower uterine segment.
AB  - AIMS: To determine interleukin (IL)-6 and IL-8 concentrations in the lower
      uterine segment in patients with chorioamnionitis compared to those without.
      METHODS: Biopsy specimens from the lower uterine segment of 33 patients with
      chorioamnionitis were matched to specimens of 33 patients without. The biopsies
      had been taken during cesarean section. The concentrations of IL-6 and IL-8 in
      protein extracts of these specimens were determined by enzyme linked
      immunosorbent assays. RESULTS: Compared to the controls patients with
      chorioamnionitis showed significantly lower gestational age and higher parity,
      and were more likely to receive fenoterol or betamethasone. In the
      chorioamnionitis group the median IL-6 concentrations were higher than in the
      controls (61.5 and 19.4 pg/mg protein, respectively [p < 0.01]). The same applies
      to the median IL-8 concentrations (162.3 and 13.4 pg/mg protein, respectively [p
      < 0.001]). CONCLUSIONS: To our knowledge this is the first study which could
      clearly demonstrate significantly increased IL-6 and IL-8 levels in the lower
      uterine segment of patients with chorioamnionitis. Increased concentrations of
      pro-inflammatory cytokines may play a pivotal role in cervical softening and
      dilatation during chorioamniotic infection.

PMID- 12235717
TI  - Tyrphostins inhibit lipopolysaccharide induced preterm labor in mice.
AB  - OBJECTIVE: We tested whether lipopolysaccharide (LPS)-induced murine preterm
      birth was delayed by tyrphostins (inhibitors of tyrosine kinases). STUDY DESIGN:
      The tyrphostins, AG126 or AG1288, or the prostaglandin endoperoxide H synthase-2
      (PGHS-2) inhibitor, NS-398, were administered 2 h before LPS, with LPS, or 2 h
      after LPS and their effect on gestational length was measured. RESULTS: Only
      tyrphostins and NS-398 administered 2 h before LPS successfully delayed preterm
      birth (p < 0.05). CONCLUSIONS: Both tyrphostins AG126 and AG1288 as well as NS
      398 inhibited LPS induced preterm birth to the time of normal birth.

PMID- 12235718
TI  - Amniotic fluid matrix metalloproteinase-8 and the development of cerebral palsy.
AB  - AIMS: To examine if increased concentrations of matrix metalloproteinase-8 (MMP
      8) in amniotic fluid are associated with the development of cerebral palsy at the
      age of three years. METHODS: The relationship between amniotic fluid
      concentrations of MMP-8 and the development of cerebral palsy was examined in 116
      preterm singleton newborns (gestational age at birth < 35 weeks) born to mothers
      who underwent amniocentesis and were followed for at least 3 years. Amniotic
      fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas. MMP-8
      concentrations were measured by specific immunoassays. Cerebral palsy was
      diagnosed by neuro developmental assessment at the age of three years. RESULTS:
      Median amniotic fluid concentration of MMP-8 was significantly higher in mothers
      whose newborns developed cerebral palsy than in mothers whose newborns did not
      develop cerebral palsy (median 153.9 [range < 0.3-1535.9] ng/ml vs median 6.4
      [range < 0.3-3836.8] ng/ml; p < 0.01). Neonates who developed cerebral palsy were
      delivered at earlier gestational age than those without cerebral palsy. After
      adjustment for the gestational age at birth and the results of amniotic fluid
      culture, elevated concentrations of amniotic fluid MMP-8 significantly increased
      the odds of development of cerebral palsy (odds ratio, 6.0; 95% confidence
      interval, 1.1-33.0; p < 0.05). CONCLUSION: Increased concentrations of amniotic
      fluid MMP-8 are associated with the subsequent development of cerebral palsy at
      the age of 3 years.

PMID- 12235719
TI  - Echocardiographic screening for congenital heart disease: a randomized study.
AB  - OBJECTIVES: To assess the effectiveness and potential cost of an
      echocardiographic screening program for congenital heart disease (CHD). PATIENTS
      AND METHODS: Between 01/11/94 and 28/02/98 there were 9697 deliveries in The
      Royal Maternity Hospital Belfast. Mothers were randomized before delivery. 4875
      infants were allocated to the scan group, while 4822 were assigned to clinical
      assessment alone. High-risk infants were considered separately. Cases of CHD
      detected before hospital discharge were documented. The annual cost of screening
      was estimated and the time to accurate diagnosis in each group was assessed.
      RESULTS: During the study 124 scan allocated infants and 50 controls were
      identified as having significant CHD before hospital discharge. With a minimum of
      3 years follow-up there were 27 additional late diagnoses in controls and 1 in
      scanned infants. During a single year of the study the mean time to complete
      diagnosis was 2 days for scanned cases and 110 in controls. The projected cost of
      screening for all infants was 22 Pounds/infant for the first year. CONCLUSIONS:
      Adding echocardiography to clinical examination greatly enhances early detection
      of CHD. Although screening is expensive, once established it may reduce the cost
      of unnecessary outpatient referrals.

PMID- 12235720
TI  - Maternal obesity not maternal glucose values correlates best with high rates of
      fetal macrosomia in pregnancies complicated by gestational diabetes.
AB  - AIM: The current therapeutic strategies to reduce macrosomia rates in gestational
      diabetes (GDM) have focused on the normalizing of maternal glucose levels. The
      aim of our study was 1.) to compare maternal glycemic values with the presence of
      fetal macrosomia at different gestational ages (GA) and with LGA at birth in a
      cohort of women with glucose intolerance and standard diabetic therapy. METHODS:
      306 women with GDM and 97 with impaired glucose tolerance underwent ultrasound
      examinations at entry and, after initiation of therapy, monthly in addition to
      standard diabetic therapy. Measurements from the entry diagnostic oGTT, glucose
      profile and HbA1c and from subsequent glucose profiles obtained within 3 days of
      the ultrasound at 5 categories of GA age (20-23, 24-27 etc) were retrospectively
      compared between pregnancies with and without fetal macrosomia, defined as an
      abdominal circumference (AC) > or = 90th percentile. Maternal prepregnancy BMI
      was adjusted for and BMI > or = 30 kg/m2 was defined as obesity. RESULTS: At
      entry, neither the hourly oGTT values, HbA1c, nor the entry glucose profile
      differed significantly between pregnancies with and without fetal macrosomia. In
      a total of 919 pairs of ultrasound/glucose profiles there was no significant
      difference in glucose levels at every GA category neither in lean nor in obese
      woman except for the fasting glucose of 32-35 GA. The fetal macrosomia rate in
      each GA category and the rate of LGA were significantly higher in obese women:
      e.g. 14.5 vs 28% at diagnosis, 15.7 vs 26.7% at 32-35 weeks, 15.5 vs 25.0% at
      birth (p < 0.05 for each comparison). CONCLUSION: The association of maternal
      glucose values and fetal macrosomia was limited to the fasting glucose values
      between 32-35 weeks while maternal obesity appeared to be a strong risk factor
      for macrosomia throughout pregnancies with GDM. In obese women the high fetal
      macrosomia rate did not appear be normalized by therapy based on maternal
      euglycemia.

PMID- 12235721
TI  - Increased endothelial thrombomodulin (TM) expression in pregnancies complicated
      by IUGR.
AB  - Thrombomodulin (TM) is a cell surface receptor playing an important role in
      endothelial cell anticoagulant activity. TM is also known as a factor of
      angiogenesis; low TM activity correlates with impaired angiogenesis. Since
      vascular lesions with disorders of the placental coagulation and inadequate
      angiogenesis can be associated with IUGR, we hypothesized that thrombomodulin
      expression in the villous vasculature and syncytiotrophoblast of placentae
      complicated by IUGR might differ from those of normal pregnancies. Representative
      tissue samples of normal, IUGR as well as 1st and 2nd trimester (n = 12)
      placentae were collected. Immunohistochemistry (APAAP) of paraffin tissue
      sections was performed using monoclonal antibodies specific for TM and PECAM. The
      percentage of immunopositive vessels and the intensity of immunoreactivity was
      assessed. Vascular endothelium and syncytiotrophoblast stained positive for TM.
      Immunoreactivity for TM in villous vasculature rose significantly with
      gestational age. Villous vessels of IUGR placentae, showed a higher expression of
      TM, compared to placentae of appropriately grown fetus (p < 0.05). The number of
      terminal villi and the number of blood vessels per intermediate villi was
      significantly reduced in IUGR placentae (p < 0.05). These differences reflect
      inadequate vascularisation and impaired angiogenesis in IUGR.

PMID- 12235722
TI  - Serum amyloid A protein in the early detection of late-onset bacterial sepsis in
      preterm infants.
AB  - In order to evaluate serum amyloid A as an early diagnostic marker of late-onset
      sepsis, seventy-nine preterm infants with clinically suspected sepsis and 40
      healthy matched controls were assayed for serum amyloid A. In parallel, clinical
      and biochemical variables that are used to evaluate neonatal sepsis were
      compared. Forty-two episodes were diagnosed as sepsis. Serum amyloid A levels
      were elevated in the sepsis group (187.6 +/- 78.3 micrograms/ml), compared with
      infants who had no sepsis (10.2 +/- 8.3 micrograms/ml) and the control group (6.9
      +/- 3.3 micrograms/ml), and were significantly higher in gram-negative compared
      to gram-positive sepsis (221.8 +/- 84.4 micrograms/ml vs. 48.5 +/- 22.2
      micrograms/ml). Analysis of the data suggests serum amyloid A has the highest
      sensitivity (100%), specificity (93%) and positive predictive value (96%) for
      sepsis among the clinical and biochemical parameters that were tested. In
      conclusion, serum amyloid A seems to be a reliable early marker for the diagnosis
      of late-onset sepsis in preterm infants.

PMID- 12235723
TI  - Carbon dioxide levels do not predict duration of home oxygen requirement: a
      retrospective study.
AB  - Knowing how long an infant with chronic lung disease (CLD) might require oxygen
      is a useful tool for counseling parents. We aimed to determine if carbon dioxide
      levels (PCO2) measured near term in newborn infants with CLD still requiring low
      flow oxygen would be useful in predicting their duration of oxygen requirement. A
      retrospective study was conducted on infants with CLD discharged from the
      neonatal unit on home oxygen treatment. The PCO2 levels of 64 infants measured by
      capillary gas after 34 weeks corrected gestation was correlated with duration of
      home oxygen requirement. We have shown that PCO2 levels measured near to term on
      a capillary gas sample in infants with chronic lung disease correlate with length
      of oxygen dependency (r = 0.55; p < 0.0001). However it was impossible to
      accurately predict the length of oxygen dependency in an individual case. We
      conclude that it would be unwise to predict an individual infant's duration of
      oxygen requirement using the PCO2 levels prior to discharge. However it might be
      possible to counsel parents in general that infants with lower PCO2 levels prior
      to discharge are likely to have their oxygen withdrawn more rapidly than those
      with higher PCO2.

PMID- 12235724
TI  - A congenital anterior diaphragmatic hernia with massive pericardial effusion
      requiring neither emergency pericardiocentesis nor operation. A case report and
      review of the literature.
AB  - All previously reported cases of anterior, diaphragmatic hernia with massive
      pericardial effusion were treated by pericardiocentesis and radical surgery
      during the early neonatal period. However, we initially followed the course of
      our patient in the neonatal period. Subsequently, elective surgery was performed
      at 70 days of age. Including our case, cardiac tamponade has not been observed in
      any previously reported cases of congenital anterior diaphragmatic hernia with
      massive pericardial effusion. CONCLUSION: Emergency pericardiocentesis and
      surgery are not always required immediately after birth, even when the presence
      of this condition is suspected by prenatal diagnosis. Our observation may be
      beneficial to preterm low birth weight infants with this condition.

PMID- 12235725
TI  - Extravascular collection of fluid around the vertebra resulting from
      malpositioning of a peripherally inserted central venous catheter in extremely
      low birth weight infants.
AB  - Peripherally inserted central venous catheters (PICCs) have allowed central
      venous access via peripheral veins for a long period. PICCs have become an
      indispensable tool in neonatal medicine. Despite their benefits, PICCs involve
      some risks, which include infection, thrombosis, malpositioning, and
      extravascular collection of fluid. We presented two patients with extravascular
      collection of fluid around the vertebra resulting from malpositioning of PICCs.
      The PICCs were placed via the saphenous veins in both patients. The PICCs were
      judged to be centrally placed in the inferior vena cava by means of supine
      abdominal roentgenograms. The next day one patient exhibited frequent apneic
      attacks and the other exhibited twitching movements. A lumbar puncture revealed
      extravascular collection of fluid around the vertebra. In lateral view chest
      abdominal roentgenograms, the PICC tips were observed to be in the vertebral
      lumen. The PICCs were removed immediately and the condition of the patients
      improved. We stressed the usefulness of the lateral view abdominal roentgenograms
      for revealing the malpositioning of PICCs in the inferior vena cava.

PMID- 12235726
TI  - Placental boost to varicella-zoster antibodies in the newborn.
AB  - IgG antibodies to varicella-zoster (VZV) were analyzed in cord and the
      corresponding maternal blood samples using the indirect fluorescence antibody
      test and the fluorescent antibody to membrane antigen test. The investigations
      revealed protective antibody levels in 96.7% of both newborns and mothers. In the
      cord blood samples, significantly higher titers were detected being indicative of
      an active placental transfer of VZV-specific IgG.

PMID- 12235727
TI  - Enhancing decision-making by depressed pregnant patients.
AB  - AIMS: We provide the reader with clinical tools for enhancing decision-making by
      depressed pregnant patients. RESULTS: Ethical principles and the concept of fetus
      as patient support four clinical strategies for enhancing the autonomy of these
      patients: screening for depression; assessing the effects of depression on
      decision-making capacity; counseling about the adverse consequences of depression
      for pregnancy; and informing patients about the options for treatment of
      depression. CONCLUSION: These four strategies can be used to prevent ethical
      conflict in decisions about the management of pregnancy in patients with
      depression.

PMID- 12235728
TI  - [Type 2 diabetes: an equivalent of coronary heart disease].

PMID- 12235729
TI  - [The pathogenesis of type 2 diabetes--new aspects and clinical consequences].
AB  - Type 2 diabetes mellitus manifests itself in individuals who lose the ability to
      produce sufficient quantities of insulin to maintain normoglycemia in the face of
      insulin resistance. The ability to secrete adequate amounts of insulin depends on
      beta-cell function and mass. The endocrine pancreas has a remarkable capacity to
      adapt to conditions of increased insulin demand and only a minority of
      individuals fail to adapt and become diabetic with time. Secondary events that
      further reduce the function of beta-cells in type 2 diabetes mellitus are the so
      called beta-cell gluco- and lipotoxicity: chronic stimulation of islets by high
      glucose and free fatty acid levels results in the reduction of insulin secretion.
      Part of these effects are reversible once these metabolites are normalized and
      the beta-cell re-exposed to a physiologic environment. The essential role of the
      beta-cell failure in type 2 diabetes is reminiscent to the pathophysiology of
      type 1 diabetes. The possible link between both diseases and the therapeutic
      implications are discussed.

PMID- 12235730
TI  - [From obesity to diabetes].
AB  - The major risk factor for the development of insulin resistance and type 2
      diabetes is obesity. A key role is the new understanding of adipocytes as an
      endocrine system. Adipocytes secrete numerous substances that contribute to
      peripheral insulin resistance, including adiponectin, resistin, TNF-alpha and
      interleukin 6. There is also a role of free fatty acids by blocking directly
      intracellular metabolism of glucose and by their lipotoxicity. The pre-receptor
      metabolism of cortisol may be enhanced in visceral adipose tissue by activation
      of 11 beta-hydroxysteroid dehydrogenase type 1. The new class of
      thiazolidinediones (glitazones), binding to the peroxisome proliferator activated
      receptor (PPAR-gamma) lowers the levels of resistin and increases adiponectin,
      resulting in an improvement of glucose homeostasis. However, the first step to
      avoid insulin resistance should be an attempt to reduce body weight and to
      increase physical activity. These are successful means to avoid the development
      of type 2 diabetes from prediabetic states, as shown recently in 3 independent
      intervention trials.

PMID- 12235731
TI  - [Differential type 2 diabetes therapy based on pathophysiological aspects].
AB  - Type 2 Diabetes is characterized by a deficit in early insulin secretion and
      increased insulin resistance. Based on the measurement of fasting and 2 h
      postprandial blood glucose a simple typing of hyperglycemia is possible in
      isolated fasting hyperglycemia (IFH), isolated postprandial hyperglycemia (IPH)
      and combined hyperglycemia (CH). IFH is predominantly associated with insulin
      resistance whereas in IPH a more pronounced insulin deficit is found. This and
      other simple parameters such as BMI, comorbidities and age are the basis of
      differential therapy with OAD if best efforts with life style modification fail
      to reach the target values of the lipid triad. Patients with IFH profit
      particularly from metformin and long acting sulfonylureas (glimepiride,
      glibenclamide). Patients with IPH are candidates for prandial antidiabetics (AGI,
      nateglinide, repaglinide). Antihyperglycemic agents such as metformin and AGI
      bear no risk of hyperglycemia and reduce body weight. Prandial insulin
      secretagogues have lower risk of weight gain and hypoglycemia than long acting
      sulfonylureas. They are therefore beneficial in obese patients and the elderly.
      The same principles are valid for combination treatment. With exception of
      insulin secretagogues all OAD can be combined if monotherapy fails to reach the
      target levels of the gluco-triad. Instead of a stepwise treatment algorithm an
      individualized therapy based on pathophysiology and comorbidities taking into
      account the global risk seems to be beneficial.

PMID- 12235732
TI  - [General insulin therapy practice in type 2 diabetes mellitus].
AB  - In most patients with Type 2 Diabetes, the primary treatment goal is near
      normoglycemia. If diet, physical activity, and oral hypoglycemic agents fail to
      achieve the individual treatment goal, insulin therapy must be considered.
      Insulin therapy in patients with Type 2 Diabetes is safe, highly efficient and
      should be initiated not too late. We recommend to perform the insulin therapy in
      Type 2 Diabetics individually upon the patients characteristics, no general
      recommendation can be given. Possible approaches to start an insulin therapy in
      general practice are discussed. Insulin therapy may be initiated as bedtime
      insulin (depot insulin at bedtime) in combination with oral agents. In patients
      who fail to achieve good glycemic control with this combination therapy, mealtime
      insulin (short-acting insulin before the meals) may be introduced instead of the
      oral agents (multiple injection regimen). Bedtime insulin may be discontinued
      when fasting glucose concentrations remain in the desired range and no rise of
      glucose concentrations occurs during the night. The two-insulin-injection regimen
      with mixed insulin formulations may be initiated in patients with Type 2 Diabetes
      when a multiple injection regimen is not feasible. The two-insulin-injection
      should not be considered as the primary insulin strategy in patients with Type 2
      Diabetes.

PMID- 12235733
TI  - [Significance of postprandial glucose peaks for development of diabetic
      macroangiopathy].
AB  - Type-2 diabetes is associated with an excessively high mortality and morbidity
      due to cardiovascular disease. Numerous studies have demonstrated the relevance
      of postprandial hyperglycemia for atherosclerosis. Moreover, the form of isolated
      postprandial diabetes seems to be much more common than expected. Even mild
      postprandial hyperglycemia in the form of impaired glucose tolerance was shown to
      be associated with an increased rate of cardiovascular disease. This indicates
      the necessity of using OGTT in the screening of high-risk populations in order to
      detect asymptomatic diabetic subjects and enable appropriate treatment in time.
      Not using the OGTT would mean missing a large cohort of undiagnosed diabetic
      subjects, particularly among older people. Since an OGTT cannot be generally
      conducted, we recommend its performance in risk subjects and especially in
      elderly women. This would make it possible to institute preventive measures.

PMID- 12235734
TI  - [Management of cardiovascular risk factors in type 2 diabetes mellitus].
AB  - Cardiovascular disease is by far the major cause of morbidity and mortality in
      subjects with diabetes mellitus type 2. The risk of cardiovascular disease in
      persons with type 2 diabetes is greater for any given risk factor, alone or in
      combination, than it is in persons without diabetes. Independent risk factors for
      cardiovascular disease in type 2 diabetes are hyperglycemia, hypertension,
      dyslipidemia and smoking. Subjects with diabetes mellitus type 2 benefit from
      cardiovascular risk factor modification, either as a primary or secondary
      intervention, as much as or more than those without diabetes. Risk factor
      modification includes behavioral modification to affect regular physical
      activity, healthy diet, weight loss, and smoking cessation. In addition, an
      optimal glycemic control with HbA1c < 7% is crucial and, aggressive management of
      hypertension (< 130/80 mmHg) and dyslipidemia are particularly important.
      Finally, aspirin (100 mg/d) is standard in secondary prophylaxis of
      cardiovascular events and should strongly be considered in primary prophylaxis if
      subjects have more than 1 concomitant cardiovascular risk factors.

PMID- 12235735
TI  - [Treatment of hypertension in type 2 diabetes mellitus--2002 update].
AB  - Arterial hypertension and diabetes are potent independent risk factors for
      cardiovascular, cerebral, renal and peripheral (atherosclerotic) vascular
      disease. The prevalence of hypertension in diabetic individuals is approximately
      twice that in the non-diabetic population. Diabetic individuals with hypertension
      have a greater risk of macrovascular and microvascular disease than normotensive
      diabetic individuals. Hypertension is a major contributor to morbidity and
      mortality in diabetes, and should be recognized and treated early. Type 2
      diabetes and hypertension share certain risk factors such as overweight, visceral
      obesity, and possibly insulin resistance. Life-style modifications (weight
      reduction, exercise, limitation of daily alcohol intake, stop smoking) are the
      foundation of hypertension and diabetes management as the definitive treatment or
      adjunctive to pharmacological therapy. Additional pharmacological therapy should
      be initiated when life-style modifications are unsuccessful or hypertension is
      too severe at the time of diagnosis. All classes of antihypertensive drugs are
      effective in controlling blood pressure in diabetic patients. For single-agent
      therapy, ACE-inhibitors, angiotensin receptor blocker, beta-blockers, and
      diuretics can be recommended. Because of concerns about the lower effectiveness
      of calcium channel blockers in decreasing coronary events and heart failure and
      in reducing progression of renal disease in diabetes, it is recommended to use
      these agents as second-line drugs for patients who cannot tolerate the other
      preferred classes or who require additional agents to achieve the target blood
      pressure. The choice depends on the patients specific treatment indications since
      each of these drugs have potential advantages and disadvantages. In patients with
      microalbuminuria or clinical nephropathy, both ACE-inhibitors and angiotensin
      receptor blockers are considered first line therapy for the prevention of and
      progression of nephropathy. Since treatment is usually life-long, cost
      effectiveness should be included in treatment evaluation.

PMID- 12235736
TI  - [Systematic aspects and therapy of diabetic neuropathy].
AB  - Diabetic neuropathy (DN) is an important complication contributing to high
      morbidity and morbidity of diabetic subjects. Primarily, interventional
      strategies aim at normalization hyperglycemia (to prevent development and
      progression of DN), at early diagnosis and at prevention of ulcers and
      amputations. In addition, an increasing number of pharmaceutical agents is used
      to symptomatically treat dysesthesia and pain associated with DN. During recent
      years attempts have been made to pharmacologically treat DN by acting on
      underlying patho-physiological mechanisms (e.g. sorbitol pathway, non-enzymatic
      glycation, microvascular abnormalities). So far, these strategies have not
      changed clinical praxis. This review will give a systematic overview of DN and
      summarize current pharmacological options to symptomatically treat dysesthesia
      and pain associated with DN.

PMID- 12235738
TI  - [Who is he to review me...!].

PMID- 12235737
TI  - [Practical management of diabetic foot].
AB  - Prevention and the correct treatment of the diabetic foot have important social
      and economic consequences. Risk stratification is essential for choosing the
      appropriate treatment strategy. History and careful clinical examination identify
      the risk in each individual patient with diabetes. Peripheral neuropathy (PNP),
      foot deformation, peripheral arterial disease (PAD) and a history of previous
      ulcer or amputation are the most important risk factors. PAD must be diagnosed
      and treated by percutan transluminal angioplasty or bypass surgery where
      necessary. Primary foot deformation or secondary due to PNP require shoe
      modifications. Good metabolic control of diabetes and treatment of other
      cardiovascular risk factors (dyslipidemia, hypertension) delay or prevent the
      development of PNP and PAD. Therefore an early multidisciplinary approach is
      essential for each patient with diabetes and foot problems. In the presence of a
      foot ulcer, it's important to diagnose osteomyelitis by clinical or radiological
      examination. The choice and duration of antibiotic treatment and surgical
      intervention depends on the localisation and extension of infection around the
      ulcer and the presence of osteomyelitis. In case of limb threatening infection,
      the patient should be referred to a specialized treatment facility immediately.

PMID- 12235739
TI  - [How to effectively control pain in dental practice].

PMID- 12235740
TI  - [Complications and mortality in surgery of cerebral aneurysms].
AB  - AIM: To establish the risk factors for complications and fatal outcome after the
      operative occlusion of cerebral aneurysms. METHODS: Retrospective study on 91
      (lethality rate) and on 72 operated patients (complications). For survived and
      dead patients, as well as for patients with and without complications, following
      parameters were compared: gender, age, clinical condition, preoperative interval,
      use of temporary clips, vasospasm, outcome, as well as localization, size and
      intraoperative rupture of the aneurysm. RESULTS: Complications existed: in 54.5%
      of aneurysms of middle cerebral and 13.6% of aneurysms of internal carotid artery
      (p < 0.01); in 18.2% of patients in the first and 45.8% of patients in the third
      clinical Hunt and Hess group (p < 0.05); in 57.9% of patients with and 20.5% of
      patients without intraoperative rupture (p < 0.01); in 50% of patients with and
      18.7% of patients without vasospasm (p < 0.05). Average aneurysmal size was 18 mm
      in group with complications and 10.8 mm in patients with no complications (p <
      0.05), while average preoperative intervals in these two groups were 20 and 8.7
      days (p < 0.05). Lethality rate was 25% for the third and 83.3% for the fourth
      and fifth clinical group (p < 0.01), and the existence of complications
      significantly increased mortality (from 15.7% to 50%, p < 0.01). Good outcome
      existed in 19.2% of operated patients with complications and in 78.3% of those
      without complications (p < 0.01). CONCLUSIONS: Incidence of complications
      depended significantly on preoperative clinical condition, duration of
      preoperative interval, size, localization and intraoperative rupture of aneurysm.
      Complications significantly minimized the surgical treatment outcome and
      increased the lethality rate mortality.

PMID- 12235741
TI  - [Reconstruction of facial defects due to war injuries using vascularized pedicled
      galeal and parietal bone grafts].
AB  - Combat wounds are basically extensive and destructive. Such injuries cause
      defects of soft and bone structures of the face and neck. During primary surgical
      management of maxillofacial combat wounds the principle of minimal bone and soft
      tissue debridment was respected. Definitive reconstruction of the defect was
      performed after two or three months, when infection was cured and adjacent
      tissues were restituted. Each combat wound leaves behind fibrous changes in
      surrounding tissues. Success of the reconstructive procedures is more certain if
      flaps with its own blood supply are used, either arterial or vascularized grafts
      from the other parts of body (by microvascular technique). This paper presents
      our experiences with galeal flap in reconstruction of facial soft tissue defects,
      as well as galea, together with external table of parietal bone in reconstruction
      of soft and bony tissues of maxillofacial in 15 patients.

PMID- 12235742
TI  - [Clinical characteristics of speech-language dysfunctions in thalamic aphasia].
AB  - The aim of this study was to investigate the characteristic symptom cluster and
      the course of aphasia in 12 patients with single left thalamic lesion verified by
      CAT scan. The testing of language disorder was performed by standard linguistic
      tests for aphasia in the acute stage and one month after the insult. Although
      this clinical syndrome varied greatly it was possible to point out some common
      characteristics. Spontaneous speech was fluent, easily articulated, grammatically
      correct, with preserved melodic line. Word finding and understanding were
      impaired. The impaired comprehension and naming were prominent in all patients
      with different severity. Repetition skills were intact. During the naming testing
      patients accomplished better results after semantic help than after phonetic
      help. Verbal paraphasia errors appeared more frequently (9.78) than neologistic
      (2.22) and literal paraphasias (1.78). Results of the language fluency tests were
      worse during semantic categorization tests (5.50) than during animal naming
      (9.89). On the basis of these facts it was presumed that aphasia in patients with
      dominant thalamic lesion was the result of lexicosemantic language disorder. It
      was statistically proved that recovery from aphasia in these cases tended to be
      significant and rapid.

PMID- 12235743
TI  - [Predictive value of changes in the hemostasis system in patients with ischemic
      brain diseases].
AB  - The aim of this research was to determine the importance of tracking the dynamics
      of changes of the hemostatic system factors (aggregation of thrombocytes, D
      dimer, PAI-1, antithrombin III, protein C and protein S, factor VII and factor
      VIII, fibrin degradation products, euglobulin test and th activated partial
      thromboplastin time--aPTPV) in relation to the level of the severity of ischaemic
      brain disorders (IBD) and the level of neurological and functional deficiency in
      the beginning of IBD manifestation from 7 to 10 days, 19 to 21 day, and after 3
      to 6 months. The research results confirmed significant predictive value of
      changes of hemostatic system with the predomination of procoagulant factors,
      together with the insufficiency of fibrinolisys. Concerning the IBD severity and
      it's outcome, the significant predictive value was shown in the higher levels of
      PAI-1 and the lower level of antithrombin III, and borderline significant value
      was shown in the accelerated aggregation of thrombocytes and the increased
      concentration of D-dimer. It could be concluded that the tracking of the dynamics
      of changes in parameters of hemostatic system proved to be an easily accessible
      method with the significant predictive value regarding the development of more
      severe. IBD cases and the outcome of the disease itself.

PMID- 12235744
TI  - [Diagnostic importance of zinc in the etiologic determination of pleural
      effusions].
AB  - Concentration of zinc in blood serum and effusion was determined in 104 patients
      with the pleural effusion of different etiology. The importance of zinc
      concentration in serum and effusion was analyzed, as well as their relation
      regarding the differential diagnosis of pleural effusion. It was established that
      the isolated zinc concentrations in serum and pleural effusion could not be used
      separately either in differing transudates from exudates or in the diagnosis of
      the pleural diseases. The average value of zinc in the pleural effusion in
      relation to the serum value in patients with tuberculosis effusion was 1.37,
      higher than 1 in all patients and was significantly different from the average
      value of the ratio 0.74 in patients with nonspecific and malignant pleural
      effusions. The relation of zinc concentration in the effusion and serum higher
      than 1.0 reliably indicated the presence of tuberculous pleurisy.

PMID- 12235745
TI  - [Use of thrombin powder after tooth extraction in patients receiving
      anticoagulant therapy].
AB  - Patients with extreme hypocoagulation, which occurs either as an effect of some
      diseases with coagulation deficiency or because of the anticoagulant therapy
      (ACT), are a risk group for oral surgery. In the last decades decision to change
      or interrupt ACT before and after the procedure was abandoned and more often
      local heamostasis was being achieved by combining chemical and biological
      substances. The success of the surgical hemostasis and thrombin powder
      combination was tested on the group of 20 patients with ACT. The results were
      satisfactory despite thrombin powder solubility in the moist oral environment.

PMID- 12235746
TI  - Testing keratolytic effect of carbamide in various vehicles.
AB  - BACKGROUND: Urea is a natural protein degradation product widely used in
      keratolytic preparations due to its property to promote fibrinogen decomposition
      and to act as a proteolytic agent dissolving and denaturing proteins.
      Preparations containing 20% or 40% urea in commercial ambiphylic bases are widely
      used to produce keratolysis. At such high concentration urea recrystallization
      occurs and is separated over the preparation mass, particularly if the urea
      content is 40%. This was the initial reason to look for a new preparation
      formulation that would not have the above-mentioned technological inadequacy.
      Considering urea's water solubility and its high content in the preparations, the
      most convenient form, in which recrystallisation would not occur, was gel. The
      aim of this work was to experimentally estimate the influence of the vehicle upon
      the proteolytic effect of urea on keratin in the human hair model. METHODS: Hair
      geometrical properties, the change in longitudinal mass, and the change of
      disruptive force and disruptive hair elongation were measured. RESULTS: The
      effect of 20% and 40% urea was estimated in three various vehicles, of which two
      were of organic hydrogel type, and one was an ambiphylic base of mixed type-
      Basiscreme. CONCLUSION: Keratin proteolysis effects of urea incorporated into
      various bases, as measured by human hair disruption forces, depended upon the
      base; preparations containing 20% and 40% urea in Basiscreme (ambiphylic base)
      had no desired proteolytic effect upon keratin fibers; proteolysis was best
      expressed bay urea preparations in 3.5% NaCMC gel, and proteolytic effect of
      these preparations was best expressed in the first hour.

PMID- 12235747
TI  - [Evaluation of sensitivity in the fasciocutaneous neurovascular medial plantar
      island flap in reconstruction of soft tissue defects in the calcaneal region].
AB  - The soft tissue cover in the calcaneal region represents one of the great
      problems in the reconstructive surgery. The distant skin, muscle and
      musculocutaneous flaps are subjected to ulcers even with the orthopedic shoes.
      The island fasciocutaneus mid sole neurocutaneous flap can be a good substitute
      for the soft tissue cover due to its anatomic structure. The flap has the
      required dimensions, sticks well to the bone and the movements and mobility of
      the patient is unrestricted. This paper analyses the sensitivity of the
      transposed flap and the sole distal to the secondary defect observed in 30
      patients. The evaluation was made after tactile tests, two-point discrimination
      test, the warm-cold test, the electrostatus of medial plantar nerve (MPN), and
      the ninhydrin test. All the tests, including the electrostatus MPN, done after 3
      weeks and 3 months after the surgery, showed successful recovery of sensitivity
      in the transposed medial plantar flap. The results monitored after three months
      showed that the speed of the neural conduction recovery was 70% of normal neural
      reaction speed of the MPN. The modified operative techniques provide safe
      dissection of the plantar nerve with minimal neuropraxia. The postoperative
      recovery of sensitivity was more rapid, and without loss of sensitivity on the
      sole.

PMID- 12235748
TI  - [Combined alpha and beta blockers in the therapy of cardiovascular diseases].

PMID- 12235749
TI  - [Population exposure to and protection from artificial ultraviolet radiation].

PMID- 12235750
TI  - [Modern antiretroviral therapy].

PMID- 12235751
TI  - [Predialysis kidney transplantation].

PMID- 12235752
TI  - [Studying the history of military medicine and surgery].

PMID- 12235753
TI  - Facility profile. Medical center takes its cue from the community. Upper
      Chesapeake Medical Center, Bel Air, Md.

PMID- 12235754
TI  - Standing out from the crowd. How ES managers can get the respect they deserve.
AB  - Environmental services professionals have a number of theories about why they
      sometimes don't get the respect and attention they deserve. "Perhaps our job is
      like being an umpire ... if we are doing it right, no one notices and they are
      allowed to simply enjoy the game (or in this case focus on wellness)," speculates
      Keith Bednar, chief environmental and support services, William S. Middleton
      Memorial Veterans Hospital, Madison, Wis.

PMID- 12235755
TI  - New vistas. Evidence-based design projects look into the links between a
      facility's environment and its care.

PMID- 12235756
TI  - Tune-up time? Recommissioning can keep your facility running efficiently.

PMID- 12235757
TI  - Ready to rumble? Hospitals grapple with seismic requirements.

PMID- 12235758
TI  - The changing role of pharmacy practice--a clinical perspective.

PMID- 12235759
TI  - The baby boom becomes the elder boom.

PMID- 12235760
TI  - Who's in charge of health?

PMID- 12235761
TI  - Integrating new technology without going broke.

PMID- 12235762
TI  - Healthier communities on the horizon.

PMID- 12235763
TI  - Population-based medicine: a winding road to nowhere?

PMID- 12235764
TI  - How long can employers hang on?

PMID- 12235765
TI  - Still no answer for the uninsured.

PMID- 12235766
TI  - The health policy home fires are still burning.

PMID- 12235767
TI  - [Brazilian Nursing Association: 75 years of democracy, ethics and cooperation
      with Brazilian nursing].

PMID- 12235768
TI  - [The "Participatory" Movement: a contribution to the history of Brazilian
      nursing].
AB  - This study outlines the beginnings and principles of the "Participatory" Movement
      (MP), which was created in opposition to the policies developed by the
      administration of the Brazilian Association of Nursing (ABEn). It starts in the
      1980's, and criticizes ABEn for: a) reproducing the official policies and the
      medical industry's interest; b) being a centralizing and authoritarian
      organization; c) focusing mainly on the scientific and cultural development of
      nurses, while minimizing the importance of political-professional reflection, as
      well as the role of the profession and professional associations in the social
      historical context; d) not participating in the formulation of public health
      policies. The "Participatory" Movement wins the elections of ABEn and takes over
      the association in 1986. The results of this new practice are still under
      construction. The achievements and withdrawals of ABEn will depend on our
      capacity of building a profession that is technically competent, critical,
      creative and, above all, socially acknowledged as an ally in the defense of the
      right to health.

PMID- 12235769
TI  - [Nursing training in Brazil in the 1970's].
AB  - The objective of this study is to revisit the period of time between 1975 and
      1979, and, within it, the history of the implantation of nursing graduation
      courses in federal universities and in geo-educational districts. It presents the
      development of a project called Projeto de Enfermagem no Grupo Setorial de Saude-
      (Nursing Project in Health) SESU/DAU/MEC (ministry of culture and education), and
      points out the social and political determinants of the, so planned, qualitative
      and quantitative development of the courses mentioned before. The research
      clarifies the proposal, process and accomplishments of the Superior Nursing
      Project of Education, which was predominantly private until 1974 and became
      predominantly public from 1976 on. Furthermore, it also indicates implications
      such as: the Commission of Nursing Education Specialists (CEEEnfermagem), which
      was linked to ABEn and was the first collective proposal of Areas and Lines of
      Research in Nursing (CNPq/CAPES/DAU/ABEn); as well as the introduction of
      institutionalized study fields in the academic institutions.

PMID- 12235770
TI  - [History of the legislation for the nursing profession in Brazil].
AB  - This article outlines the contribution of the Brazilian Association of Nursing
      (ABEn) in the study, discussion and approval of laws and regulations that have
      significant impact on the nursing profession. It points out that ABEn has always
      had an active, pacific and accurate way of working. It emphasizes that the
      association has dealt with de law making-body and executive members of the
      government, based on technical arguments and secondary data in order to comply
      with the nursing professional's needs.

PMID- 12235771
TI  - [The Brazilian Nursing Association in the creation, implementation and
      development of nursing boards].
AB  - The Brazilian Association of Nursing (ABEn) was founded in 1926. The association
      has been the source for the creation of new professional organizations and the
      motivator of the development of the nursing profession in the country. The
      creation, implantation and development of the nursing boards are important
      achievements of ABEn. Twenty-eight years of struggle to approve the law number
      5.905 of 12 July 1973, which created the nursing boards. Implantation of the
      Federal Board of Nursing (COFEn) and CORENS done under the leadership of ABEn.
      ABEn's participation in the development of the federal and regional boards of
      nursing. Current situation of the relationship between ABEn, syndicates, and
      nursing boards.

PMID- 12235772
TI  - [The "Participatory" Movement].
AB  - This study reports the trajectory of the Participatory Movement (MP), which was
      created in opposition to the policies carried out by the Brazilian Association of
      Nursing (ABEn). This article, written by the first president elected of the
      "participatory" movement, presents the principles of the movement, its
      organization, the struggle for leadership, and the work developed in the first
      administration.

PMID- 12235773
TI  - [Psychiatric nursing and modern nursing in Rio de Janeiro: a history lesson].
AB  - The present study is the result of an essay written for the discipline Research
      Laboratory of Nursing History. It refers to the interest and struggle of the
      Brazilian Association of Nursing (ABEN), in the 1940s, in Rio de Janeiro, to make
      professionals of this area aware of the need of the inclusion of nursing in the
      psychiatric field in Rio de Janeiro. Our objective is to present the difficulties
      of this insertion, although the beginnings and the regulation of the nursing
      profession in Brazil started in a school of nursing, in the Psychiatric Hospital
      of Rio de Janeiro. In order to present the difficulties for this inclusion, we
      analyzed the documents that prescribed the regulation of the nursing profession,
      in the psychiatric area of the hospital mentioned above. Results indicate that
      standards established by Anna Nery Nursing School were broken, since psychiatric
      assistance was denied by this school until 1949, while the Nursing School Alfredo
      Pinto provided this kind of care since 1890. It is important to point out the
      strategic and historical role of ABEn as the coordinator and motivator of
      discussions regarding the course of the nursing profession.

PMID- 12235774
TI  - [The Brazilian Nurses Association and the development of nursing in Brazil--a
      path under construction].
AB  - Through the concept of memory by Walter Benjamin, the authors of the present
      study identify relevant facts of the Brazilian Association of Nursing (ABEn) that
      affected the development of nursing in Brazil. The investigation points out the
      participation of ABEn in the regulation of the nursing field, creation of Revista
      Brasileira de Enfermagem (Brazilian Journal of Nursing), promotion of the
      Congressos Brasileiros de Enfermagem (Brazilian Congresses of Nursing) and its
      importance on the political struggle for better health conditions in Brazil.

PMID- 12235775
TI  - [The participation of Sister Mathilde de Nina in the historical construction of
      the Brazilian Nurses Association].
AB  - The present work is a study of social-historical nature. It has as its objective
      understanding the participation of Sister Mathilde Nina, as a representative of
      the Companhia das Filhas da Caridade (Daughters of Charity Company), in the
      history of the Brazilian Association of Nursing (ABEn). It discusses the
      association of this sister to ABEn as a way of spreading the catholic ideology.
      The study covers a period of time between 1939 and 1950. The primary data was
      collected through written documents and reports of people who were close to
      Mathilde Nina. The dialectic method was adopted and the discussion of the
      findings is based on Pierre Bourdieu's thoughts. As a consequence of the edict
      20.109/31, the Sisters of Charity made their insertion in the formal education in
      Brazil. As the first representative of the Company to graduate, sister Nina could
      perform in different instances of the nursing profession. Her participation in
      ABEn was a way of spreading the catholic ideology in nursing.

PMID- 12235776
TI  - [Telling a beautiful story: the trajectory of the Brazilian Nurses Association
      Bahia].
AB  - This study presents the story of the Brazilian Association of Nursing in Bahia
      federal state. It parallels the trajectory of this association to the history of
      the National Brazilian Association of Nursing, pointing out the most important
      events in its fifty-three years of work. It is clear that the history of the
      Brazilian Association of Trained Nurses (ABED)/ABEn-Bahia begins with the
      foundation of the Nursing School of the Federal University of Bahia. Teachers at
      this university, who were nurses in their home states, and had participated in
      other associations previously, were motivated to create a new branch of ABEn in
      Bahia. The branch of ABEn in the city of Feira de Santana-Bahia, had a similar
      trajectory, since it was also founded after the creation of the State University
      of Feira de Santana. The branch of ABEn in Bahia is considered a democratic
      association, which is attentive to the claims of the nursing professionals, the
      health of the Brazilian population and also to the strengthening of the
      organization.

PMID- 12235777
TI  - [Revealing the nurses participation in the Brazilian Nurses Association-Cascavel
      region].
AB  - The objective of the present research is to identify the reasons for the scarce
      participation of nursing professionals in the Brazilian Association of Nursing
      (ABEn) and other professional associations. The data was collected from nurses in
      the city of Cascavel-Parana and was analysed according to qualitative and
      quantitative methods. Results show that a small number of professionals take part
      in the events promoted by ABEn-Cascavel and that there is little interest in
      joining any professional association. 36.6%, of nurses interviewed showed
      interest in becoming members of ABEn. Thus, for these professionals ABEn should
      define strategies of inclusion. The data collected in this research, regarding
      the reasons for the participation of nurses in the association, has provided ABEN
      Cascavel with information that can support its performance in the city, as well
      as help on the planning of new activities and policies such as the promotion of
      events and changes on the price of the tuition, which was pointed out as one of
      the main reasons for the scarce participation of nurses in the association.

PMID- 12235778
TI  - [Brazilian Nursing Association-Ceara Chapter: a journey through history].
AB  - In this study, the members of the Brazilian Association of Nursing (ABEn) in
      Ceara federal state present aspects of the history of this association along its
      fifty years of work. The information, facts and pictures collected for this study
      were obtained from documents available in the branch, as well as from semi
      structure interviews applied to former presidents of the association. The
      objective of the interviews was to understand the peculiarities of the experience
      of these administrators during their participation in the association.

PMID- 12235779
TI  - [1986-2001: Ideals and dreams reached in 15 years of campaigns, work and
      achievements of the Brazilian Association of Nursing-Itajuba region].
AB  - The present article reports the trajectory of a regional branch of the Brazilian
      Association of Nursing (ABEn) in Itajuba. It shows the development of this
      association since its inception until the present days. The study also depicts
      how the efforts invested and the success obtained helped on the development and
      strengthening of the nursing work in the south region of Minas Gerais.

PMID- 12235780
TI  - [Recount of the history of the Brazilian Nurses Association in Paraiba].
AB  - The purpose of the present study is to outline the trajectory of the Brazilian
      Association of Nursing(ABEn) in the federal state of Paraiba, from its foundation
      until the present days. Based on bibliographic review and on the analysis of
      meeting minute the investigation reports the historical antecedents and the
      foundation and development of the Nursing School of Paraiba and ABEn. It also
      points out the organizational structures and events, which were important
      landmarks in the history of this nursing association.

PMID- 12235781
TI  - [The history of nursing in Pernambuco: a glance at the Brazilian Nurses
      Association].
AB  - This article contributes to the history of nursing, as it points out the
      discussion of issues, landmarks and influences promoted by the Brazilian
      Association of Nursing (ABEn) in the federal state of Pernambuco, in the period
      of 1968 until 1972. Through direct interviews and the analysis of secondary data
      it was possible to perceive the importance of this association in matters such as
      rights, regulation and development of the nursing profession, as well as the
      promotion of sociocultural and educational activities for these professionals in
      Pernambuco.

PMID- 12235782
TI  - [Telling a history ... the creation process of the Brazilian Nurses Association
      Rio Grande do Sul Chapter].
AB  - This work is a description of the most relevant facts of the branch of the
      Brazilian Association of Nursing (ABEn) in Rio Grande do Sul federal state, along
      its fifty years of work. The data was collected in primary sources such as
      records of the association, newspaper articles, congress minutes, reports from
      ABEn's members, and pictures. The study contextualizes nursing in the period,
      which precedes the creation of this branch. It presents biographical aspects of
      the first directors of the association. Reports the trajectory of this branch,
      focusing on its struggle to legitimate the nursing profession as a profession
      that demands higher education and to include it in the career plans of public and
      private organizations. Describes the efforts of the association to meet the
      demands of the professional and educational legislation. Presents the work done
      to strengthen ABEn-Rio Grande do Sul through the organization of campaigns,
      scientific events and the event Semana da Enfermagem (congress of nursing). It
      also acknowledges the decisive role of ABEn-RS in the creation and consolidation
      of the Syndicate of Nursing and of the Federal/Regional Board of Nursing. Finally
      the study demonstrates that, although it defends specific professional interests,
      it also has a profound commitment with the quality of the health service provided
      in Brazil.

PMID- 12235783
TI  - [The contribution of the Brazilian Nurses Association-Santa Catarina in the 75
      years of the Brazilian Nurses Association].
AB  - The present work describes the trajectory of the Brazilian Association of Nursing
      (ABEn) in Santa Catarina since its inception on 13 March 1962, until the present
      days. It refers to the precarious situation of nursing in the 1960's and the
      insufficiency of professionals in that federal state, as the main reasons for the
      creation of the branch in that state. The activities developed by ABEn-SC are
      reported in this study in order to reveal the nature and political position of
      the association towards social impacts and public departments. The study explains
      the means used to give publicity and to up-date the profession and the events
      that this association has carried out or cooperated with. It also makes reference
      to the partners that have given support to the ABEn-SC and the way it has
      promoted its activities.

PMID- 12235784
TI  - [Brazilian Nurses Association-Sao Paulo. Notes on the contributions to the
      Brazilian nursing].
AB  - In this article four directors of the Brazilian Association of Nursing (ABEn)-SP
      report meaningful aspects of the history of this institution along its 56 years.
      The information, facts and pictures were organized based on documents and on a
      manuscript written by one of the first directors of the association. The article
      is permeated of personal impressions regarding the authors' experiences in ABEn.

PMID- 12235785
TI  - [Brazilian Nurses Association Sergipe Chapter: 47 years of struggle and
      resistance].
AB  - This work outlines the facts that contributed for the creation of the Brazilian
      Association of Nursing in Sergipe. It reports the trajectory, contributions and
      main accomplishments of ABEN in that state, pointing out its participation in the
      foundation and organization of services and institutions. The study also mentions
      the difficulties faced by ABEn-Sergipe, but mainly, it emphasizes the struggle of
      the association for maintaining its principles, its role in the social and
      cultural organization of the syndicate, and the availability of the nursing
      service for the community.

PMID- 12235786
TI  - [Future of bacteriology from the viewpoint of clinical microbiology].

PMID- 12235787
TI  - [Future of bacteriology from the viewpoint of genomic drug design and development
      of anti-infective agents].

PMID- 12235788
TI  - [Bacterial flagella].

PMID- 12235789
TI  - [On what I learned from researches on Huntington's disease].
AB  - In the Presidential Lecture, I looked back my 28 years' history of researches on
      Huntington's disease (HD). In the first 3-4 years, I worked predominantly in the
      field of the neuro-anatomy, elucidating the fine distribution of the inhibitory
      neurotransmitter, GABA, in the human substantia nigra, elucidating the existence
      of a hitherto unknown subthalamo-nigral pathway in rat, and demonstrating the
      presence of the excitatory substance P-ergic striatonigral pathway in rat. In the
      middle 16-17 years, I preferentially worked in the field of neurochemical
      pharmacology, suggesting a mechanism of chorea in HD to be a result of
      hyperactivity of remaining presynaptic dopaminergic system in the striatum by
      making a 'choreic' model in monkey using excitotoxic kainic acid and levodopa. In
      the last 7-8 years, we began to be involved in the analysis of huntington gene of
      patients and protein chemistry of intranuclear inclusion bodies appeared in
      culture cells, based on the concept that HD is a CAG repeat disease. We found
      that the forming process of inclusion bodies was unexpectedly rapid. In addition,
      we found that inclusion bodies not only contain huntington itself but also
      contain histones, splicosomes, and ubiquitin. The recruitment of those
      biologically important proteins into the inclusion bodies could give neurons
      serious damages for living normally, even if not directly to a catastrophe, a
      neuronal death.

PMID- 12235790
TI  - [Neural stem cells: the basic biology and prospects for brain repair].
AB  - Neural stem cells (NSCs) are multipotential progenitor cells that have self
      renewal activities. A single NSC is capable of generating various kinds of cells
      within the CNS, including neurons, astrocytes, and oligodendrocytes. Because of
      these characteristics, there is an increasing interest in NSCs and neural
      progenitor cells from the aspects of both basic developmental biology and
      therapeutic applications to the damaged brain. By understanding of nature of NSCs
      present in CNS, extracellular factors and signal transduction cascades involved
      in the differentiation and maintenance of NSCs, population dynamics and
      localizations of NSCs in embryonic and adult brains, prospective identification
      and isolation of NSCs, and induction of NSCs into particular neuronal phenotypes,
      which will be introduced in this review, it would be possible to develop a
      feasible strategy to manipulate cells in situ to treat the damaged brain.

PMID- 12235791
TI  - [Neural and molecular mechanisms of visual memory and imagery in the primate].
AB  - In this talk, I examined the cortical mechanisms involved in the memory formation
      and activation for visual images. Our ability to "see with the mind's eye" has
      been of interest to philosophers and scientists for a long time. Today we have a
      variety of approaches (including neuroimaging, electrophysiological,
      psychophysical and neuropsychological methods) to investigate where and how the
      images of objects, scenes and living beings are generated, stored and maintained
      in the brain. The aim of my study is to provide the solid neurophysiological
      basis for these studies. I first devised an animal model of imagery task: Macaque
      monkeys were trained to memorize visual objects in associative memory and to
      retrieve the image of an object from long-term storage according to an
      associative cue. I addressed the following basic questions, and described the
      answers we obtained: (1) Where in the brain is the mnemonic representation of
      visual images stored and how is it organized? (2) How is the representation
      created and what is the molecular basis of neural circuit reorganization? (3)
      Which neural circuits enable the reactivation of the image representation and the
      memory retrieval? (See for further details. http://www.physiol.m.u-tokyo.ac.jp/).

PMID- 12235792
TI  - [Brain attack in Japan, now and future].
AB  - In Japan, all of the stroke center hospital equipped by high level diagnostic
      systems including MRI. Number of MRI is twice as that of U.S.A. Therefore, we can
      perform correct and effective treatment for ultra-acute cerebral infarction if rt
      PA is permitted to clinical use for cerebral infarction. We are making Japan
      Standard Stroke Registry Study (JSSR Study) now, and already registered 2,740
      acute stroke cases in 25 hospitals. Atherothrombotic embolism (artery to artery
      embolism) was found in 16.5% of the all atherothrombotic infarction. It suggests
      that diagnostic accuracy of our database is high level. Concerning with ultra
      acute thrombolysis, about 10,000 stroke patients per year are estimated to be
      treatable with rt-PA in Japan. Yamaguchi's study for acute cerebral infarction
      showed intra-arterial thrombolytic therapy using urokinase was significantly
      effective. Our JSSR Study also showed effectiveness of thrombolytic therapy using
      rt-PA or high dose urokinase in the patients with cerebral infarction treated
      within 6 hours. Therapeutic time windows for acute cerebral infarction using rt
      PA is expected to be more longer by the newly developed free radical scavenger
      (edarabin). We must create evidence based medicine for Japanese stroke patients
      based on database system (JSSR).

PMID- 12235793
TI  - [Targets of treatment in the acute phase of cerebral infarction].
AB  - In the acute phase of cerebral infarction, many experimental data suggest that
      free radicals including superoxide, hydroxy radical and nitric oxide are one of
      the most important factors to cause brain damage. We have clearly detected
      nitrotyrosine (a marker of endogenous production of peroxynitrite, which is
      readily produced from superoxide and nitric oxide) in neurons and
      intraparenchymal vascular walls during post-ischemic reperfusion. Free radical
      scavengers thus seem to be very promising tools of treatment, and one of them
      (edaravone) has recently been approved for clinical use in Japan. CREB (cyclic
      AMP response element binding protein) is a DNA-binding transcription factor, and
      its function is activated by phosphorylation of Ser133 residue. CREB plays
      important roles in neuronal development, synaptic plasticity and regeneration. We
      have found that phosphorylation of CREB is significantly and persistently
      increased in surviving neurons and oligodendrocytes in post-ischemic brain, while
      this phosphorylation is only transiently increased in neurons and
      oligodendrocytes which eventually die. These data suggest that CREB
      phosphorylation plays an important role in protection of ischemic brain tissue.
      Oligodendrocyte progenitor cells (OPC) remain abundant throughout the adult
      brain, and retain their ability to become not only mature oligodendrocytes, but
      also neurons. We have recently found that OPC are significantly activated and
      proliferate in the peri-infarct area at 1-2 weeks after ischemia, suggesting that
      OPC may be involved in the repair mechanisms of ischemic brain. Future targets of
      stroke treatment should include enhancement of intrinsic protection mechanisms
      such as CREB phosphorylation and activation of progenitors cells.

PMID- 12235795
TI  - [Neuroprotective therapy for the treatment of acute ischemic stroke].
AB  - Following cerebral ischemia, various biochemical reactions are provoked in a
      stepwise manner leading neuronal cells to ischemic death. The prevention of these
      biochemical reactions may exert neuroprotective actions and consequently reduce
      the magnitude of ischemic cerebral injury. On the basis of such a view, numerous
      neuroprotective drugs have been developed during the last decade. Quite a few
      drugs were found effective in reducing the infarct volume in experimental
      studies, and more than 15 of them were subjected to clinical phase III trials to
      see a therapeutic effectiveness. However, the results of phase III trials were
      disappointing in the majority drugs. Only three drugs, nicaravene, ebselen and
      edaravone, all radical scavengers, were judged effective by small-sized trials
      with a wide therapeutic window, 48-72 hours after stroke, in Japan. The fact
      suggests that a one-point prevention of biochemical reactions by single drug is
      unable to rescue ischemic neuronal cells. Ischemic insult causes damages of
      vascular wall including the endothelium which play an important role in the
      development of hemorrhagic changes or cerebral edema. Vascular protection is
      considered as important as neuroprotection in treatment of clinical stroke. Mild
      hypothermia has neuroprotective and vascular protective actions and hence may be
      more effective than neuroprotective drugs for the treatment of stroke. The
      prevention of fever, which often occurs in severe stroke, may exert the similar
      effect as hypothermia in neuroprotection. Neuroprotective therapy in the future
      should proceed toward the simultaneous protections of neurons and vessels using
      combination of multiple drugs.

PMID- 12235794
TI  - [Strategy for circulatory disturbance].
AB  - A meta-analysis by the Cochrane Stroke Group (CSG) showed that thrombolytic
      therapy increased deaths as well as symptomatic and fatal intracranial hemorrhage
      within the first seven to 10 days and at final follow-up, although these risks
      are offset by a reduction in disability in survivors, so that there is overall a
      significant net reduction in the proportion of patients dead or dependent. Trials
      testing intravenous (i.v.) tPA suggest that it may be associated with less hazard
      and more benefit. A recent trial demonstrated that intra-arterial pro-urokinase
      improved long-term outcome in patients with M 1 or M 2 occlusion within 6 hours
      of onset. Trials of the third generation of thrombolytic agents are ongoing in
      patients with acute ischemic stroke. The latest CSG's meta-analysis showed that
      immediate anticoagulant therapy in patients with acute ischemic stroke was not
      associated with net short or long-term benefit because there was no evidence that
      anticoagulant therapy reduced deaths or non-fatal stroke during treatment or
      patients dead or dependent at the end of follow-up. However, an i.v. low
      molecular-weight heparinoid showed a trend toward improving long-term outcome in
      subgroup of patients with atherothrombotic stroke. The thrombin inhibitor
      argatroban was proven to be comparable to the thromboxane A2 synthetase inhibitor
      ozagrel in the effect on the outcome at one month in patients with
      atherothrombotic stroke within 48 hours of onset in Japan, and a trial of the
      agent is ongoing in patients with ischemic stroke within 12 hours of onset in the
      United States. Two large trials of aspirin in patients with ischemic stroke
      within 48 hours of onset indicated that aspirin had a modest effect on reducing
      patients dead or dependent at the end of follow-up. An international trial of
      abciximab, a monoclonal antibody directed against platelet glycoprotein IIb/IIIa,
      is ongoing in patients with ischemic stroke within 6 hours of onset.

PMID- 12235796
TI  - [Molecular mechanisms of neurodegeneration in dentatorubral-pallidoluysian
      atrophy (DRPLA)].
AB  - Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant
      neurodegenerative disorder characterized by various combinations of cerebellar
      ataxia, choreoathetosis, myoclonus, epilepsy, dementia and psychiatric symptoms.
      With the discovery of the gene for DRPLA in 1994, molecular mechanisms of
      neurodegeneration has been intensively investigated. Expression of truncated
      DRPLA proteins in cultured cell has been shown to result in aggregate body
      formation and apoptosis. We have developed transgenic mice for DRPLA (Q129 mice).
      The Q129 mice showed a severe neurological phenotype characterized by ataxia,
      myoclonus and seizures. Although numerous neuronal intranuclear inclusions (NIIs)
      were observed in the brain, obvious neuronal loss was not observed. NIIs,
      however, appeared much later than the phenotypic presentations, and intranuclear
      accumulation (diffuse nuclear staining) of mutant proteins was the earliest
      phenomenon. These results suggest that "neuronal dysfunction", but not "neuronal
      cell death", is responsible for the phenotypes. Hypothesizing that nuclear
      proteins interacting with expanded polyglutamine stretches are involved in the
      pathogenesis, we found that that expanded polyglutamine stretches preferentially
      bind to TAF130, a cofactor involved in CREB-dependent transcriptional activation,
      and strongly suppressed CREB-dependent transcriptional activation. Taken
      together, these findings suggest that the interference of CREB-dependent
      transcription by expanded polyglutamine stretches is involved in the neuronal
      dysfunction in polyglutamine diseases.

PMID- 12235797
TI  - [Cell death protection by anti-apoptotic factor].
AB  - Neurodegenerative disorders including ALS and Parkinson's disease are
      characterized by progressive loss of neuronal cell death. Apoptosis, a
      morphologically and biochemically defined form of cell death caused by active
      cellular signaling, has been long implicated in neurodegeneration. Recently, the
      basic molecular mechanism of apoptosis has been elucidated and a subset of
      cysteine proteases called caspases were shown to be the executioner of apoptosis.
      On the other hand, endogenous caspase inhibitor called inhibitor of apoptosis
      proteins (IAPs) were also identified. XIAP, the most potent apoptosis inhibitor
      among human IAPs, is shown to be direct and selective inhibitor for caspase-3, -7
      and -9. We have very recently shown that XIAP has ubiquitin ligase activity which
      promotes the degradation of caspase-3 and this protease activity enhances the
      anti-apoptotic activity of XIAP. Regarding the involvement of apoptosis in
      neurodegenerative diseases, several lines of evidence indicated that caspases are
      involved in the pathogenesis of ALS and polyglutamine disease, suggesting the
      effectiveness of anti-apoptotic therapy for these diseases. Moreover, caspase
      independent programmed cell death is also suggested to be involved in
      neurodegenerative disorders. Based on these findings, the therapeutic strategy
      for neurodegenerative disease should include both anti-apoptotic and anti-non
      apoptotic cell death treatments.

PMID- 12235798
TI  - [Molecular pathogenesis of motor neuron disease].
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that
      selectively involves motor neurons. About ninety percent of ALS patients are non
      hereditary sporadic cases, the molecular pathogenesis of which is unknown. One of
      the effective approach to analyze the molecular pathology is to analyze the gene
      expression profiles of the neurons being involved in ALS and compare them to
      those of the intact neurons. The genes whose expression levels are specifically
      altered in ALS tissues are likely to be the candidate molecules which are related
      to the molecular pathogenesis of motor neuron degeneration. We have been
      examining the spinal cord tissues from the ALS and control autopsied cases by the
      methods of molecular indexing and cDNA microarray analysis. We have screened more
      than 10,000 genes, and obtained several novel genes the expression levels of
      which are altered in ALS tissues. We are now still ongoing to analyze the
      function of these genes as well as a role in pathophysiology in ALS.

PMID- 12235800
TI  - [Sensory-motor disintegration in the basal ganglia disorders].
AB  - Basal ganglia lie between the cerebral cortex and the thalamus, and have dense
      fiber connections between them. These connections form 4-5 distinct loops to
      allow parallel processing of information. Among them, the most intensively
      studied is the motor loop, which comprises 2 distinct direct and indirect
      pathways. The direct pathway disinhibits the powerful inhibition of Gpi/SNr upon
      the thalamic VL nuclei with a net result of facilitatory influence upon the motor
      cortex. By contrast, the indirect pathway exerts an inhibitory effect. Overall
      this dual system provides a center-surround mechanism to focus its effect on
      selected cortical neurons. The functional role of the loop in motor control has
      not been precisely understood. Several lines of evidence have recently been
      presented to support the view that this mechanism is used to focus the output to
      a specific group of muscles required for performing a specific task. Recent
      observations in dystonia and Parkinsonism suggest that this operation is made
      possible through opening the sensory channel for the expected sensory feed-back
      afferents during movement. Thus one of the important functions of basal ganglia
      seems to be the gating of sensory input for motor control.

PMID- 12235799
TI  - [The ubiquitin-proteasome system and neurodegeneration].
AB  - Many studies have suggested the ubiquitin-proteasome system played an essential
      role in the pathogenesis of neurodegenerative disorders. In 1999, we provided
      evidence that a mutation of the system could directly cause neurodegeneration
      using the gad mouse. Namely, we identified the gad mutation was caused by an
      intragenic deletion of a gene encoding ubiquitin C-terminal hydrolase 1(UCH-L1),
      which is a member of de-ubiquitinating enzyme family. In human, missense mutation
      of UCH-L1 gene was reported in a German family with Parkinson's disease. As well,
      the parkin gene product was revealed to be an E3 ubiquitin ligase which recognize
      a form of alpha-synuclein as a substrate. Thus, the investigation of the
      ubiquitin-proteasome system should provide a clue for understanding
      neurodegeneration. We have characterized UCH-L1 and identified candidates of
      endogenous substrates as well as interacting proteins of UCH-L1. In addition, we
      found amount of monomeric ubiquitin was decreased in the brain of the gad mouse
      compared with wild type mice. We have also tried to develop "protein therapy"
      using UCH-L1 protein with TAT sequence. We observed the protein was delivered to
      brain after intraperitoneal injection in the wild type mouse. This approach would
      provide a new therapeutic strategy for neurodegeneration.

PMID- 12235801
TI  - [Deep brain stimulation therapy for involuntary movements].
AB  - During the last decade, it has become clear that deep brain stimulation (DBS)
      therapy provides a dramatic improvement in the symptoms of movement disorders. We
      have experienced DBS in 110 patients with various types of involuntary movements,
      and confirmed the benefits of stimulation of the thalamic nucleus ventralis
      intermedius (Vim), internal globus pallidus (GPi) and subthalamic nucleus (STN)
      in these patients. DBS therapy affords the best effect on tremor when the Vim is
      selected as the stimulation site. DBS therapy is also useful for controlling
      rigidity when the GPi or STN is stimulated. Improvements of bradykinesia and gait
      disturbance are often induced by DBS therapy involving the GPi or STN. Dopa
      induced dyskinesia can be attenuated effectively by the direct and/or indirect
      effects of DBS therapy. DBS of the Vim also provides excellent control of post
      stroke involuntary movements, including hemiballism and hemichoreoathetosis.
      Dystonia in young patients is controlled effectively by DBS of GPi. Ablative
      procedures for control of involuntary movement disorders, such as thalamotomy and
      pallidotomy, always carry a risk associated with creating additional lesions in
      an already damaged brain. In contrast, there is not such a risk in DBS therapy.
      This modality of therapy is an important option in treating involuntary
      movements.

PMID- 12235802
TI  - [Pharmacological aspect of the mechanism and the treatment of involuntary
      movements].

PMID- 12235803
TI  - [Transcranial magnetic stimulation (TMS) in movement disorders].
AB  - Transcranial magnetic stimulation (TMS) has been used to study several aspects of
      movement disorders: central motor conduction time (CMCT), electromyographic (EMG)
      silence evoked by TMS, reset of tremor rhythm by TMS, GABAergic inhibitory
      interneuronal function of the motor cortex studied with paired-pulse TMS. In this
      communication, We briefly summarize results of paired-pulse TMS in movement
      disorders. NORMAL SUBJECTS: A subthreshold conditioning stimulus over the motor
      cortex reduced the size of EMG responses to a succeeding suprathreshold test
      stimulus given to the same motor cortex. This inhibition is considered to be an
      inhibitory effect on the motor cortex because the same conditioning stimulus has
      no influence on H-reflexes or electrical cortical responses. Pharmacological
      effects on this inhibition suggested that it is mediated by GABAergic inhibitory
      systems in the motor cortex. PATIENTS: The cortical inhibition was reduced in
      cortical myoclonus, which is consistent with the notion that the studied effect
      is mediated by GABAergic systems. The inhibition was disturbed in focal dystonia,
      whereas normal inhibition was elicited in Segawa's disease. Reduced inhibition
      was seen in Parkinson's disease (PD), whereas normal inhibition in essential
      tremor. Normal inhibition was evoked in all patients with chorea. Abnormal
      inhibition in basal ganglia disorders must reflect damaged movement selection in
      the motor cortex secondary to the primary lesion in the basal ganglia. This
      abnormality occurs in some movement disorders and does not occur in the others,
      which indicates different pathomechanisms for involuntary movements. It is
      conspicuous that normal inhibition was evoked in Segawa's disease even though the
      patients had dystonia.

PMID- 12235804
TI  - [Antiepileptic drug therapy for adult patients with intractable seizures].
AB  - Epileptic syndrome, antiepileptic drug (AED) therapy and mental disorder were
      studied in 223 patients with intractable epilepsy, who were admitted to our
      epilepsy center between 1992 and 2000. Symptomatic localization-related epilepsy
      was diagnosed in 86.1% of patients, symptomatic or cryptogenic generalized
      epilepsy in 7.6%, idiopathic generalized epilepsy in 1.8%, unclassifiable
      epilepsy in 3.1% and non-epilepsy in 1.3% on discharge. Only 6.3% had diagnoses
      on discharge that were incongruent with their diagnoses on admission. AED therapy
      during admission improved markedly in 50% of patients and moderately in 20%,
      however, 60% had seizures more frequently than 4 a month on discharge.
      Generalized tonic and clonic seizures were suppressed completely in 82.5% of
      patients. The number of AEDs used were 2 AEDs in 28.6%, 3 in 39.1% and 4 in
      22.3%. Only 6.4% of patients were on monotherapy on discharge. Mental retardation
      was in 58.7%, schizophrenia-like psychosis in 8.5%, delusional disorder in 1.8%,
      mood disorder in 3.6%, AED-related disorder in 14.3% and psychogenic disorders in
      21.5%. AED therapy is effective for intractable seizures, but it is limited in
      its effect. Mental disorders also coexisted in most of patients. Therefore
      comprehensive therapy of epilepsy is necessary for patients with intractable
      seizures.

PMID- 12235806
TI  - [Surgical treatment for intractable epilepsy].
AB  - Epilepsy surgery can be divided into two categories, resective and disconnective
      procedures. The former includes lesionectomy, corticectomy, and lobectomy. The
      latter comprises MST (multiple subpial transection), corpus callosotomy, and
      hemispherotomy. In this presentation, the preoperative diagnosis and surgical
      outcomes of temporal lobectomy and MST will be illustrated. Temporal lobe
      epilepsy is one of the most common seizures in adult intractable epilepsy.
      Noninvasive preoperative evaluation, including analysis of seizure semiology,
      repetitive scalp EEG, and MR imaging, can definitely localize the seizure focus,
      without depending on invasive monitoring, in 70% of the cases. Seizure outcome
      after temporal lobectomy is generally satisfactory, with 70% seizure-free and >
      90% significantly improved. However, verbal amnesia is an unavoidable sequela
      when the focus is on the speech-dominant side and preoperative MRI reveals little
      or no hippocampal atrophy. MST is an epoch-making surgical technique by which
      surgical treatment of eloquent cortex has become possible. In cases with
      neocortical epilepsy treated by MST alone or combined with corticectomy, 80%
      showed significant improvement, that is compatible with reported outcomes of
      corticectomy. MST can be also applied to treatments of extensive epileptic foci,
      Rasmussen's encephalitis, or Landau-Kleffner syndrome.

PMID- 12235805
TI  - [Clinical features and treatment of refractory epilepsy in children].
AB  - Clinical features of refractory epilepsy in children are symptomatic localization
      related epilepsy, especially frontal lobe epilepsy, the onset in young age less
      than 3 years-old, and complication of developmental retardation. The treatments
      usually start with one drug of choice for specific seizure type. In the
      idiopathic epilepsy group, valproic acid was effective in 82% of the patients
      with generalized epilepsy and in 45% of localization-related epilepsy while
      carbamazepine was effective in 71% and 67%, respectively. However, in the
      refractory group which did not react to the drugs of choice at the initial
      treatment and continued to have seizures, no specific drugs were effective.
      Therefore, various kind of drugs, new or old, should be tried in sequence
      irrespective of the type of seizures. The seizure control was attained only in
      10% (in the cases of CZP), and 17% (CLB) in localization-related epilepsy and in
      9% (VPA), 12% (NZP) and 20% (ZNS) in generalized one in the refractory group.
      Although new drugs developed, the patients with refractory epilepsy do not tend
      to decrease in frequency and overall management including daily life or surgical
      therapy is mandatory for the children with refractory epilepsy.

PMID- 12235807
TI  - [Treatment of status epilepticus].
AB  - Status epilepticus (SE) is a condition requiring emergency care. There are
      convulsive SE, non-convulsive SE including complex partial status and absence
      status, non-convulsive electric SE and pseudostatus epilepticus, although
      convulsive SE is the most common. Diagnosis of status epilepticus of complex
      partial seizures (CPS) and absence seizures was significantly delayed because
      delays in seeking medical attention were common. The seizures were generalized
      convulsive SE in 84% and CPS status in 16%, and the overall mortality rate was
      15% in 41 SE patients of our study. EEG monitoring is important to make or
      exclude the diagnosis of SE. Diazepam is the first choice medication and
      effective in the management of SE, and lately, lorazepam, midazolam, propofol and
      pentobarbital etc as emergency therapy. Phenytoin is also considered first-line
      agent in the emergency management of SE. Repetitive transcranial magnetic
      stimulation (rTMS) led to a prolonged latency for seizure induction after an
      intraperitoneal injection of pentylenetetrazol (PTZ) and effectively prevented
      the development of status epilepticus of PTZ-induced convulsions in the rats. Our
      data suggest that rTMS has suppressive effects on the neuronal excitability in
      rats. These effects are anticonvulsive and suggest the possibility of therapeutic
      use of rTMS in the patients with refractory seizures.

PMID- 12235808
TI  - [Dynamic neuropathology of tauopathy].
AB  - Tauopathy is defined as abnormal accumulation of aberrantly phosphorylated
      microtubule-associated protein tau in the central nervous system, best
      demonstrated by immunocytochemistry using anti-tau antibodies. The newly
      recognized familial tauopathy with mutation in tau gene, that is located on
      chromosome 17, confirms that the process directly leads to neuronal degeneration.
      Tau consists of six isoforms translated from alternative splicing of a single
      gene. They are classified into three repeat (3R) and four repeat (4R) subtypes,
      by the number of microtubulus-binding domain from the reading or skipping of the
      exon 10. In sporadic tauopathy, 3R + 4R accumulate in Alzehimer's disease (AD),
      3R in Pick's disease, and 4R in progressive supranuclear palsy (PSP) and
      corticobasal degeneration (CBD). In familial tauopathy, the mutations affecting
      the splicing of the exon 10 accumulate 4R and phenotypically mimick CBD/PSP,
      while majority of others simulate neurofibrillary tangle-predominant form of
      dementia (NFTD). Argyrophlic grains (AG) are tau-immunoreactive comma-shaped or
      filiform structure, and argyrophilic grain dementia (AGD) is a form of senile
      dementia carrying AG as only morphological substrate explaining dementia. In our
      consecutive autopsy cases from the oldest old, AGD is the second leading cause of
      degenerative type of dementia, highlighting the importance of tauopathy in the
      aging and dementia.

PMID- 12235809
TI  - [Visualization of tau isoforms by splicing-site specific antibodies].
AB  - We have developed five tau antibodies that recognize each of 6 human tau isoforms
      to examine tau lesions such as Alzheimer's neurofibrillary tangles (NFTs) in
      Alzheimer's disease (AD) as well as other tauopachies. These five antibodies were
      designed to be specific to splicing-sites of exon 2, exon 3, or exon10 or to the
      amino acid sequence in exon 3 or exon10. All of newly prepared antibodies as well
      as anti-human tau stained corresponding recombinant tau isoforms and isolated
      hyperphosphorylated tau isoforms in an isoform-specific manner on western blot.
      All antibodies were also found to decorate immunohistochemically NFTs but to be
      present in unequal amounts in NFTs where two tau isoforms (tau1-352 and tau1-381)
      were the major species. It is not easy to compare immunoreaction based on
      immunohistochemical analysis with multiple antibodies. However, the present
      result strongly suggest unequal occurrence of tau isoforms in Alzheimer's NFTs,
      indicating other isoform selection in AD than tauopathies.

PMID- 12235810
TI  - [Molecular analysis of tau deposited in the FTDP-17 brain].
AB  - Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is a
      familial neurological disorder, characterized genetically by autosomal dominant
      inheritance, clinically by behavioral abnormalities and parkinsonism, and
      neuropathologically by tauopathy. Linkage analyses of affected families have led
      to identification of many exonic and intronic mutations in the tau gene. Using
      site-specific antibodies that distinguish between wild-type and mutant tau, we
      analyzed molecular species of tau in the soluble and insoluble fractions of the
      brain affected by two FTDP-17 mutations, P301L and R406W. Western blotting showed
      that mutant tau was preferentially deposited in the Sarkosyl-insoluble fraction
      of the P301L brain. Consistent with this, immunocytochemistry showed that
      intraneuronal tau deposits consisted exclusively of mutant tau. On the other
      hand, the protein levels of mutant tau in the soluble fraction were selectively
      decreased despite no detectable decrease in its mRNA levels. In contrast, almost
      equal amounts of wild-type and mutant tau were present in the Sarkosyl-insoluble
      fraction of the R406W brain and their levels in the soluble fraction did not
      differ from each other. Wild-type and mutant tau colocalized in neurofibrillary
      tangles in the frontotemporal cortices. In contrast to soluble R406W tau, which
      was less phosphorylated than soluble wild-type tau. Sarkosyl-insoluble R406W tau
      was highly phosphorylated to a similar extent as insoluble wild-type tau.

PMID- 12235811
TI  - [Analysis of mouse model exhibiting neurofibrillary changes].
AB  - Dysfunction and filamentous microtubule-binding tau protein are key markers of
      neurodegenerative pathologies, including the pathology and neural degeneration
      associated with Alzheimer's disease (AD). Immunocytochemical studies of NFT
      bearing neurons showed that NFTs are composed of ubiquitin and phosphorylation
      dependent tau. Congo-red birefringency and thioflavin-S reactivity in NFT-bearing
      neurons also demonstrated that the tau aggregation forms a beta-sheet structure.
      Discovery of the molecular mechanisms of NFT formation may lead to more insight
      about events occurring during neurodegeneration. In frontotemporal dementia
      parkinsonism 17 (FTDP17), genetic studies indicated that tau is a causative gene,
      and mutation is found in exons and introns of tau gene. A patient who possesses
      this mutation exhibits pathologically NFT and clinically personality change and
      cognitive dysfunction. Then, we produced the Tg mice expressing human longest tau
      with missense mutation V337M. In the present study, neurons of hippocampus and
      cerebral cortex in our Tg mice showed phosphorylated and ubiquitinated tau
      aggregations with a beta-sheet structure. This was demonstrated by Congo-red and
      thioflavin-S positive staining, a histological criterion used to identify NFTs
      observed in neurodegenerative disorders. The mice also displayed altered
      behaviors that were associated with NFT formation. Thus, V337M mice provide a
      first animal model exhibiting altered behavior due to NFTs.

PMID- 12235812
TI  - [Hereditary ataxias-overview].
AB  - Many of autosomal dominant spinocerebellar ataxias (SCA) are now shown to result
      from the expansion of unstable trinucleotide repeats. In most SCAs, these repeats
      are present within coding sequences of the causative genes and translated into
      polyglutamine tracts. In this overview clinical and molecular genetic features of
      newly identified group of diseases in this category are briefly summarized.
      Expanded polyglutamine repeats are supposed to mediate some toxic effects on a
      certain population of neurons that result in neuronal dysfunction. The current
      progress in these molecular biological studies on their pathophysiology is also
      reviewed. In Japan, Friedreich ataxia with intoronic GAA repeat expansions has
      not been known. Instead, early onset ataxia with Friedreich phenotype, associated
      with ocular motor apraxia in childhood and with hypoalbuminemia in adult, is the
      predominant ataxia with Friedreich phenotype, the causative mutation of which was
      very recently identified.

PMID- 12235813
TI  - [Autosomal dominant cortical cerebellar atrophy (ADCCA) linked to chromosome
      16q].
AB  - Clinical features of and genetic approach identifying the gene for autosomal
      dominant cortical cerebellar atrophy linked to chromosome 16q (16q-ADCCA) are
      presented. The clinical characteristics of our 6 families with 16q-ADCCA were
      slowly progressive pure cerebellar syndrome with late age of onset (average +/-
      SD years: 55.9 +/- 10.0), which contrasts with more earlier onset, prominent
      sensory neuropathy and pyramidal tract signs seen in spinocerebellar ataxia type
      4 (SCA4) linked to the same chromosomal region. To identify the gene responsible
      for 16q-ADCCA, we refined the previously mapped region and found that all of our
      6 families share haplotype for markers lying in about 3-cM region in 16q31-q22,
      indicating that the founder effect is present in this disease. We next
      constructed a BAC contig spanning this 3-cM region. The maximum size of this
      contig was estimated 5 megabase (Mb). By searching public genome databases, we
      first examined for the presence for expansion of tandem repeat sequences in our
      patients. We found more than 50 tandem repeats including 8 CAG repeats. However,
      we have not detected any expansion in our patients so far. We are currently
      examining remaining repeat sequences for expansion and also several genes that
      appear potential candidates from their expression and functional profiles.

PMID- 12235814
TI  - [Spinocerebellar ataxia type 10 (SCA10): a disease caused by a novel
      pentanucleotide repeat expansion].
AB  - Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant progressive
      disorder characterized by ataxia, seizures and anticipation, mapped to chromosome
      22q13.3. We have found that the mutation of SCA10 is an unstable and massive
      expansion (800-4,500 repeats) of the ATTCT pentanucleotide repeat in intron 9 of
      SCA 10 (also known as E46L), a novel gene of unknown function. The mutation, so
      far, has only been found in the population of the Mexican descent with a founder
      effect supported by haplotype data. The expansion size of the repeat inversely
      correlates with age of disease onset and SCA10 is highly expressed throughout the
      central nervous system. Expanded ATTCT repeats in SCA10 patients show repeat size
      instability in their somatic and germline cells as well as time-dependent
      instability in blood. This novel type of microsatellite repeat expansion is the
      largest found to date in human diseases. Its epidemiological, clinical, genetic
      and pathophysiological features need to be further investigated.

PMID- 12235815
TI  - [SCA17, a novel polyglutamine disease caused by the expansion of polyglutamine
      tracts in TATA-binding protein].
AB  - We have recently identified a novel SCA form in nine patients from four Japanese
      pedigrees through the screening for expanded polyglutamine tracts by Western
      blotting analysis with a monoclonal 1 C 2 antibody that recognizes specifically
      pathological polyglutamine tracts. This disease is caused by an abnormal CAG/CAA
      expansion in the TATA-binding protein gene (TBP), a general transcription
      initiation factor. This abnormal expansion of glutamine tracts in TBP ranges 47
      to 55 repeats, whereas the normal repeat number ranges from 29 to 42.
      Immunocytochemical examination of a postmortem brain that carried 48 CAG repeats
      detected neuronal intranuclear inclusion bodies (NIIs) that stained with anti
      ubiquitin antibody, anti-TBP antibody and with the 1 C 2 antibody. Most patients
      presented in the third decade with gait ataxia and dementia, progressing over
      several decades to include bradykinesia, dysmetria, dysdiadockokinesis,
      hyperreflexia and paucity of movement. No abnormal eye movements were present in
      any patient. This disease resembles the spinocerebellar ataxias including Dentato
      rubal pallidoluysian atrophy (DRPLA) more closely than any other form of
      neurodegenerative disorder. Further study of this disease should provide
      important information for unraveling the molecular pathogenesis of neuronal cell
      degeneration as well as for the development of future therapeutic interventions.

PMID- 12235816
TI  - [Lateralization and interhemispheric integration of directed attention].
AB  - Directed attention is a function to direct and shift the focus of awareness
      adequately to behaviorally relevant sensory events. Healthy subjects direct
      attention evenly to right and left hemispaces. Unilateral spatial neglect is a
      failure to respond normally to stimuli on the side opposite a cerebral lesion,
      which is considered to represent a unilateral disruption of directed attention.
      The established clinical observation that neglect usually occurs after right
      hemisphere lesions and the results of functional imaging studies suggest the
      right hemisphere dominance for directed attention. It is hypothesized that the
      right hemisphere distributes attention to space bilaterally, whereas the left
      hemisphere distributes attention primarily to right hemispace. However, patients
      with callosotomy show no apparent neglect with either right or left hand. Ishiai
      et al. (2001) reported detailed analyses of eye movements when a patient with a
      callosal infarction bisected lines. Left unilateral spatial neglect may appear,
      when use of the right hand induces a rightward bias in the attentional control of
      the left hemisphere and damage to its cingulate gyrus inhibits interhemispheric
      integration of attention. By contrast, the disconnected but intact right
      hemisphere may bisect a line accurately by integrating attention to the extents
      perceived in the left and right visual fields.

PMID- 12235817
TI  - [Selective visual attention and simultanagnosia].
AB  - The parietal lobe is an important key station in the network for selective
      attention. We found that spontaneous shift of visual attention, depending on task
      requirement, was impaired by parietal lobe lesions and confirmed the relationship
      between parietal lobes and visual attention with cortical electric stimulation.
      Patient 1. A 52-year-old, right-handed carpenter with a diagnosis of 'visual
      form' of Alzheimer disease showed marked kanji (logogram) agraphia and
      constructional impairment. Cerebral atrophy and hypoperfusion were observed in
      bilateral parietal lobes. He showed preserved form and color perception and an
      ability to describe spatial relationship among several items. In contrast, he
      could not copy or match them. He seemed to look at only the site he was drawing.
      Patient 2. A 77-year-old man with cerebral infarction in bilateral parietal lobes
      and right frontotemporal areas, demonstrated simultanagnosia and visuomotor
      ataxia. He readily named an object but could not describe a scene. Furthermore he
      noticed a line between sentences when they were written in English, but could not
      notice a line when sentences were written in Japanese. Cortical electric mapping,
      in two patients with subdural electrodes on the left or right parietal lobe,
      revealed circumscribed regions related to global/local attention shift or line
      bisection tasks.

PMID- 12235818
TI  - [Prefrontal lobes and the attentional control: a neuropsychological study using
      modified Stroop test].
AB  - The prefrontal lobes may play an important role in attentional and cognitive
      control. The modified Stroop test can detect the disorder of this regulatory
      function in the brain-damaged patients. The Stroop conflict task was given to 35
      prefrontal damaged patients (prefrontal group) and 20 subjects with temporal or
      parietal lesions (posterior group). The prefrontal subjects were further divided
      into the three subgroups, which consisted of 17 dorsolateral, 6 medial and 12
      orbitofrontal patients. There were no significant differences between the
      prefrontal and posterior group on the Stroop test. However, the dorsolateral
      prefrontal damaged subgroup and the medial prefrontal damaged subgroup had
      significantly poor performances than the posterior group on the incongruent
      condition of the Stroop test. This findings indicated that the impairment of
      attentional control between the word reading and color naming resulted from the
      lesions of dorsolateral and medial part of prefrontal lobes. The cognitive
      control of visual attention may be supported by the neural substrates including
      dorsolateral prefrontal lobe, supplementary motor area and anterior cingulate
      cortex.

PMID- 12235819
TI  - [Functional imaging studies of attention].
AB  - Functional organization of the human brain involved in attention has been
      determined in many human brain imaging studies. Most of these studies focused on
      brain mechanism related to selective attention using different sensory modality
      or sub-modality stimuli. Recently, we have shown other aspects of human
      attentional system, that is spatial attention, using event-related functional
      MRI. In this study, using delayed sequential saccade paradigm, subjects were
      forced to pay their attention towards right or left visual field. We could not
      find significant difference in brain activation patterns between right and left
      visual field attention tasks. The results are inconsistent to the findings of the
      previous lesion studies of humans showing spatial neglect. Further collaborative
      studies of neurological and brain mapping researches should be necessary to
      understand human higher cognitive functions.

PMID- 12235820
TI  - [Pathogenetic mechanisms of autoimmune neuropathies caused by antiglycolipid
      antibodies].
AB  - Antiglycolipid antibody titers are frequently elevated in the serum of patients
      with autoimmune neuropathies. Some antibodies may be involved in the pathogenesis
      because glycolipids are surface antigens in the nervous system. Sensory ataxic
      neuropathy was induced in rabbits sensitized with GD1b ganglioside, which is
      localized in the rabbit primary sensory neurons of the larger cytoplasms.
      Systemic infusion of high-titer anti-GD1b antiserum to rabbits pre-inoculated
      with adjuvant caused vacuolar degeneration with macrophage infiltration in a few
      axons in the dorsal column of the spinal cord. Anti-GD1b antibody therefore may
      cause degeneration in rabbit sensory neurons with central axons extending to the
      dorsal column. Investigations on the clinical features of GBS patients with
      monospecific anti-GD1b IgG antibodies showed that the antibodies are associated
      with sensory disturbance, especially disturbance in the deep sensation, and with
      primary demyelinating form. GD1b is localized in primary sensory neurons and
      paranodal myelin in the human peripheral nervous system. Monospecific anti-GD1b
      IgG antibodies may bind to those regions and be involved in the pathogenesis of
      sensory disturbance and demyelination. Thus, some antiglycolipid antibodies may
      determine the clinical features of GBS by binding to the regions where the
      antigens are localized.

PMID- 12235821
TI  - [Vascular endothelial growth factor and Crow-Fukase syndrome].
AB  - Serum vascular endothelial growth factor (VEGF) is highly elevated in patients
      with Crow-Fukase syndrome (CFS) and is well correlated with the clinical
      manifestations of CFS. In circulating blood, VEGF is specifically stored in
      platelets and released during platelet aggregation. To clarify the role of VEGF
      in the pathomechanism of CFS, we transplanted VEGF secretion tumors in nude mice
      and studied the pathological findings in these mice. Prominent edema with
      elevated serum VEGF were found. Organomegaly was also found in liver, spleen and
      kidney. Pathological findings in these organs were similar to those found in
      autopsies of CFS patients. In peripheral nerve, mild intraneural edema was seen,
      however, neuropathy was not prominent. These findings suggest that elevated VEGF
      may be closely correlated with generalized edema (anasarca). However, it is also
      important to consider factors such as cytokines and other T cell functions that,
      in association with VEGF, may be the cause of neuropathy in CFS.

PMID- 12235822
TI  - [Central nervous system involvement in Behcet's disease].
AB  - Central nervous system involvement in Behcet's disease, usually called neuro
      Behcet's syndrome (NB), includes acute type and chronic progressive type. Acute
      NB is characterized by acute meningoencephalitis with focal lesions, presenting
      high intensity areas in T2-weightened images or FLAIR images on MRI scans.
      Cyclosporin A frequently causes acute NB. Acute NB responds to steroid therapy,
      and is usually self-limiting. By contrast, chronic progressive NB is
      characterized by intractable slowly progressive dementia, ataxia and dysarthria
      with persistent elevation of cerebrospinal fluid IL-6 activity (more than 20
      pg/ml). In our series, most patients (approximately 90%) with chronic progressive
      NB were HLA-B51 positive, and had history of attacks of acute NB prior to the
      development of progressive neurological symptoms. Chronic progressive NB is
      resistant to conventional treatment with steroid, cyclophosphamide, or
      azathioprine. However, recent studies suggest the efficacy of low dose
      methotrexate in chronic progressive NB.

PMID- 12235823
TI  - [A study on pathomechanisms of paraneoplastic neurological syndrome].
AB  - Paraneoplastic neurological syndrome is thought to be caused by an autoimmune
      mechanism triggered by tumor antigens which attack the neurons presenting the
      common antigens. We tried to prove the antibody-mediated neuronal loss by passive
      transfer with IgG containing Yo antibody or Hu antibody and active immunization
      with recombinant Yo protein or Hu protein. But in fact the antibody per se did
      not cause neuronal loss. On the other hand, the patients with paraneoplastic
      neurological syndrome show pleocytosis in the cerebrospinal fluid and massive
      lymphorrhage, predominant CD8+ T cells, are seen in the tumor and in the lesions
      in the central nervous system. Another observation that each of the patients'
      group with anti-Yo antibody positive paraneoplastic cerebellar degeneration or
      anti-Hu positive sensory neuronopathy have the common HLA class I supertype,
      suggested the neuronal loss might be caused by class I restricted CD8-positive
      cytotoxic T lymphocytes (CTL). We synthesized the peptides from Yo or Hu protein
      with binding capacity to each of the class I molecules. We found the CTL
      activities in the peripheral CD8+ T cells against the matched peptide-presenting
      autologous fibroblasts. We need to prove the CTL attacks neurons directly.

PMID- 12235824
TI  - [Development of new therapy on muscular dystrophy].
AB  - Duchenne muscular dystrophy (DMD) is an X-linked, lethal disorder caused by a
      defect in the DMD gene. We have previously reported that micro-dystrophins, which
      have large deletions in rod repeat domain, successfully localize at the
      sarcolemma and stabilize dystroglycan-sarcoglycan complex in dystrophin-deficient
      mdx muscle. However, expression of a 3.7-kb micro-dystrophin cDNA, having only
      one rod repeat showed no effect on dystrophic phenotype. Further transgenic
      experiments are carrying to seek a functional but small-sized micro-dystrophin
      cDNA, which can be accommodated into Adeno-associated virus (AAV) vector. In
      normal muscle, AAV-LacZ vector expresses stably beta-gal for a long period,
      however, we noticed that immune response is evoked by AAV-LacZ vector in mdx
      muscle. Therefore, for successful gene therapy, it is required to reduce immune
      response against AAV-dystrophin vector and therapeutic proteins in mdx mice. We
      have already reported that utrophin was up-regulated at the sarcolemma of mdx
      mice, when a beta-galactosidase-expressing adenovirus vector, AxCALacZ was
      injected into the skeletal muscle. Moreover, up-regulated utrophin mitigated
      dystrophic phenotypes. Up-regulation of utrophin was induced by inflammatory
      response against adenovirus vector-mediated gene transfer and this up-regulation
      is one of promising tools for treatment of DMD.

PMID- 12235825
TI  - [Gene therapy for Parkinson's disease: studies in animal models].
AB  - Recent developments in viral vectors capable of providing high levels of long
      term transgene expression in the brain have led to the pursuit of two strategies
      in gene therapy for the treatment of Parkinson's disease (PD). One is the local
      production of dopamine in the striatum achieved by inducing the expression of
      dopamine-synthesizing enzymes. Three enzymes are necessary for efficient dopamine
      synthesis: tyrosine hydroxylase (TH) converts tyrosine to L-DOPA, aromatic L
      amino acid decarboxylase (AADC) then converts L-DOPA to dopamine, and guanosine
      triphosphate cyclohydrolase I (GCH) is the rate-limiting enzyme for the synthesis
      of TH co-factor tetrahydrobiopterine. We have previously demonstrated that
      transduction with separate adeno-associated virus (AAV) vectors expressing TH,
      AADC, and GCH is effective in reducing motor abnormalities in 6-hydroxydopamine
      lesioned rats and in MPTP-treated monkeys. Behavioral recovery persisted for at
      least 18 months after intrastriatal injection in parkinsonian rats. In MPTP
      monkeys, the amelioration of motor abnormalities was remarkable on the
      contralateral side, accompanied by robust transgene expression and elevated
      dopamine synthesis in the AAV-injected putamen. The second strategy entails the
      expression of neurotrophic factors or brain vesicular monoamine transporter in
      the striatum or the substantia nigra to slow the degeneration of dopamine
      neurons. Gene therapy using viral vectors offers a promising approach in the
      treatment of PD patients.

PMID- 12235826
TI  - [Gene therapy and neurotrophic factor treatment for amyotrophic lateral
      sclerosis].
AB  - Although excitotoxic and oxidative stress play important roles in spinal neuron
      death, the exact mechanisms are not fully understood. We examined cell damage of
      primary culture of 11-day-old rat spinal cord by addition of glutamate, nitric
      oxide (NO) or peroxynitrite (PN) with detection of terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL). With addition
      of glutamate, NOC18 (a slow NO releaser) or PN, TUNEL positive nuclei were found
      in spinal large motor neurons from 24 h, and the positive cell proportion greatly
      increased at 48 h in contrast to the vehicle. The present results suggest that
      both excitotoxic and oxidative stress play important role in the apoptotic
      pathway in cultured rat spinal neurons. To examine a possible protective effect
      of exogenous glial cell line-derived neurotrophic factor (GDNF) gene expression
      in transgenic (Tg) mice carrying a Gly 93Ala (G93A) mutant SOD1 gene found in
      human familial ALS, a replication defective adenoviral vector containing GDNF
      gene was directly injected unilaterally into leg muscles. There were
      significantly more large motoneurons in GDNF-treated Tg mice than in untreated
      and Ad-Laz-treated group. The number of large motoneurons in GDNF-treated side of
      Tg mice were significantly more than that in untreated side. These observations
      demonstrate that GDNF gene therapy in a mouse model of FALS promotes the survival
      of motoneurons, suggesting that a similar approach might delay the progression of
      neurodegeneration of ALS.

PMID- 12235827
TI  - [Therapeutic strategy for multiple sclerosis targeting NK and NKT cells].
AB  - Recent works from our laboratory have demonstrated that natural killer (NK) cells
      and CD1d-restricted NKT cells are functionally biased toward producing type 2
      cytokine in the remission phase of multiple sclerosis, an autoimmune disease
      putatively mediated by Th1 T cells. Indirect evidence would indicate that the
      type 2 bias of NK and NKT cells is not the cause of MS but an adaptive change to
      protect against activation of pathogenic Th1 cells. In fact, NK cells biased for
      producing IL-5 (NK2 cells) would inhibit induction of Th1 cells in vitro. Here I
      propose that it is a reasonable strategy for the control of MS to maximize and/or
      optimize the regulatory potentials of the innate regulatory cells. We have
      already found that experimental autoimmune encephalomyelitis (EAE), an animal
      model for MS, can be inhibited when NKT cells are partially stimulated by
      glycolipid ligands for NKT cells. Experiments proved that the suppression of
      disease is mediated by IL-4 produced by NKT cells. Future studies should be
      directed for identifying useful ligands for inducing regulatory cytokines from NK
      and NKT cells.

PMID- 12235828
TI  - [The right hemisphere language].
AB  - A large number of observations since the mid-nineteenth century have shown that
      damage to the left but not the right hemisphere destroys language function. These
      observations lead to the formation of the "classic" view that the left hemisphere
      has language function but not the right hemisphere. It thus came as a
      considerable surprise in the early 1960's when tests on commissurotomy or split
      brain patients suggested the presence of a considerable capacity for reading
      comprehension in the right hemisphere. It has been suggested that the spared
      regions in the left hemisphere normally act to prevent the expression of latent
      language functions within the undamaged right hemisphere. Thus, only after the
      intact right hemisphere has been released from the disruptive and suppressive
      influences of the damaged left hemisphere by section of the corpus callosum, can
      its own residual function become effective. Some investigators have argued,
      however, that the split-brain evidence is misleading because the language of the
      split-brain patients is presented in both hemispheres even pre-operatively. Our
      investigation with functional MRI is in progress to decide which hypothesis is
      appropriate. In addition to the functional MRI study of split-brain patient, the
      functional MRI study of aphasia recovery will also provide opportunities to
      clarify the right hemisphere language function since the right hemisphere is
      generally intact in the right-handed aphasic.

PMID- 12235829
TI  - [Clinically useful event-related potentials].
AB  - For clinical use of event-related potentials (ERPs), issues to be solved included
      individual variations in their latencies and amplitudes, inconsistencies in the
      abnormalities of these parameters in dementia patients among research institutes,
      etc. In normal groups, variations in the latency and amplitude of P300 (P3), a
      representative ERP component, can be resolved by the standardization of several
      of its biological determinants. The determinants included 1) natural factors,
      e.g. circadian rhythm, the season, 2) induced factors, e.g. exercise, fatigue,
      drugs, and 3) constitutional factors, e.g. age, sex. The inconsistency of data
      among dementia patients is mostly due to differences in the severity or stage of
      dementia. However, clinically the most important issue is to develop an ERP test
      to identify mild cognitive dysfunction at an early stage of dementia, which
      differs from that at an advanced stage. For example, in familial Alzheimer's
      disease, a test for verbal memory is reported to be the most sensitive. On the
      other hand, mismatch negativity, one of the early ERP components, is a pre
      attentive automatic response to changes in auditory stimuli. Since this component
      can be evoked without any attention or task, one of its advantages is that it can
      be recorded in infants or small children, or in demented or comatose patients.
      Other clinically useful ERP components are also introduced.

PMID- 12235830
TI  - [Neuro-infections to be borne in mind].
AB  - We presented atypical manifestations in tuberculous meningitis (TbM) and herpes
      simplex encephalitis (HSE), lymphocytic dominant cerebrospinal fluid pleocytosis
      in bacterial meningitis, and a hitherto easily overlooked critical illness
      polyneuropathy (CIP) associated with sepsis. 1) We presented 2 TbM patients with
      atypical manifestations. One patient was a 25-year-old man who exhibited
      polymorphonuclear (PMN) dominant pleocytosis in CSF throughout his clinical
      course. He died the next day after a CSF culture yielded the growth of
      tuberculous bacilli, before receiving appropriate anti-TBM therapy. This was a
      rare TbM example of persistent PMN dominant CSF pleocytosis. The other patient
      was a 39-year-old woman whose CSF pleocytosis changed from lymphocytic dominant
      to PMN dominant about 1 month after the initiation of antituberculous
      chemotherapy. This CSF change was followed by multiple cerebral infarcts due to
      vauculitis caused by TbM. Administration of prednisolone caused marked
      improvement of the patient's symptomatology. Tuberculomas appeared transiently
      during anti-TbM therapy, consistent with paradoxical progression of tuberculoma.
      2) A few patients with HSE may show atypical CSF findings such as PMN dominant
      pleocytosis, absence of pleocytosis, and low sugar value. Our national survey of
      HSE patients showed following percentages of these atypical findings: PMN
      dominant pleocytosis observed in 10% of the patients in the early stage and at
      the time of exacerbation, no pleocytosis in 0.9% (1 patient), and low sugar value
      in 4%. 3) Bacterial meningitis typically causes PMN dominant CSF pleocytosis.
      However, Listeria meningitis (LM) may cause lymphocytic dominant pleocytosis in
      30% of the patients, particularly in elderly ones. We showed one such 69-year-old
      patient with persistent lymphocytic dominant CSF pleocytosis throughout the
      clinical course. 4) CIP, septic encephalopathy and critical illness myopathy are
      3 major complications associated with sepsis. CIP is a frequent cause of
      neuromuscular weakness due to axonal dysfunction, which occurs to critically ill
      patients with sepsis, particularly when multiple organ dysfunctions are present.
      We showed our CIP patient associated with acute bacterial endocarditis and
      multiple organ failure. We should bear in mind these atypical manifestations, and
      frequent and important complications associated with sepsis such as CIP, to
      provide appropriate management to patients with neuro-infection and sepsis.

PMID- 12235831
TI  - [Pitfalls in MR imaging of neurological diseases].
AB  - MR imaging is useful for the diagnosis of neurological diseases but it has many
      pitfalls. The author presented one patient with syringobulbia of whom
      neurological examinations revealed lesions in the medulla. MR images showed slit
      like lesions in the medulla and pontine tegmentum of which signal intensity was
      similar to that of cerebrospinal fluid. However, a sagittal scout image reveals
      syringomyelia in the upper cervical spinal cord that was important abnormal
      finding for the diagnosis of this case. In a case of hypertrophic cranial
      pachymeningitis, neurological examinations showed right lower cranial palsies and
      MR images showed lesions along the right temporal bone with T1- and T2
      shortening. After injection of the contrast medium, abnormal contrast enhancement
      was observed in the medial side of the lesions. In the anterior cranial fossa,
      however, the anterior falx was thick and it showed low signal on T2-weighted
      images and abnormal contrast enhancement. These findings of the falx indicated
      that the patient had hypertrophic cranial pachymeningitis. It is important to see
      lesions which neurological examinations detect. However, all of the images must
      be seen, because in the distant location, the key findings for the diagnosis may
      be present.

PMID- 12235832
TI  - [Medical treatment of dystonia].
AB  - The treatment of dystonia is exclusively difficult. Recently botulinum toxin has
      been introduced into the market, but its indication is still limited. Oral
      administration of high dosage of anticholinergic drugs is firstly recommended for
      the treatment of dystonia. Effective cases usually do not show obvious side
      effects. Likely, diazepam is another choice, and the drug usually does not bring
      any adverse effect in cases with good results. Effects of other drugs such as l
      dopa and antidopaminergic agents are still under discussion. In cases with
      myoclonus and/or tremor clonazepam can be useful for improvement of the phasic
      symptoms. As the prognosis of dystonia especially that of focal dystonia is not
      hopeless, the patients with dystonia should be informed of the facts.

PMID- 12235833
TI  - [Clinical progress in headache].
AB  - In Western communities, 15 to 20% of the general population experiences migraine
      headaches. In Japan, 3 to 9% of the population experience migraine headaches.
      Quality of life in headache patients is impaired. The International Headache
      Society (IHS) published the new headache classification in 1988. Chronic daily
      headache (CDH) is a common problem in headache clinics. Recently, the problems in
      classifying CDH have been discussed. CDH is not easily classified within the IHS
      criteria. For migraine attacks, triptans are effective. The genetic analysis in
      migraine is progressing. Point mutations in the P/Q-type Ca2+ channel alpha 1
      subunit gene in familial hemiplegic migraine and in Notch 3 gene in cerebral
      autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
      (CADASIL), have been identified. Although CADASIL patients in Europe often show
      migraine headache, migraine attacks are less common in Japanese CADASIL patients.

PMID- 12235834
TI  - [Genetic testing and bioethics].
AB  - Genetic counseling is fundamental before and after the genetic testing,
      especially presymptomatic genetic testing. However, there is no official system
      for genetic counseling in Japan. We propose the multidisciplinary approach to
      genetic counseling, which might become available in the Japanese medical system.
      Shinshu University Hospital established a division of clinical and molecular
      genetics as one of its central service departments in 1996. It was officially
      approved by Ministry of Education in 2000. Our division is composed of several
      MDs from the departments of neurology, endocrinology, pediatrics, oncology,
      laboratory medicine and medical genetics, a clinical psychologist, and a genetic
      nurse. We have a staff meeting once a week to discuss each case for providing the
      suitable counseling, and we discuss the ethical, legal and social issues (ELSI).
      We hope our approach will become familiar to other hospitals, and genetic
      services in Japan will consequently be improved.

PMID- 12235835
TI  - [Diagnosis and treatment of brain stem infarction].

PMID- 12235836
TI  - [Recent advances in limb-girdle muscular dystrophy research].
AB  - In our laboratory, limb-girdle muscular dystrophy (LGMD) accounted for 20% of all
      patients with muscular dystrophy. To determine the incidence of various forms of
      LGMD phenotypes, we looked for mutations in the calpain 3 gene and, for
      deficiencies in dysferlin and sarcoglycan by immunohistochemical studies with
      specific antibodies on muscle biopsies from patients with probable autosomal
      recessive inheritance (LGMD2), which were mostly sporadic cases of LGMD. Fourteen
      of 276 (5%) patients examined had sarcoglycan complex deficiency
      (sarcoglycanopathy) and 21 of 80 (26%) had mutations in the calpain 3 gene.
      Although we have not performed gene analysis in all patients, 10 of 64 (15%)
      patients examined had no apparent immunoreactivity against the dysferlin
      antibody. Thus, approximately 46% of LGMD2 patients had the above 3 distinct
      disorders, but in 54% the causative defects remain unknown.

PMID- 12235837
TI  - [Beta-amyloid protein: recent progress in basic research and therapeutic
      approaches].
AB  - Deposition of amyloid beta protein (A beta) as senile plaques or cerebrovascular
      amyloid characterizes the brains of patients with Alzheimer's disease (AD). A
      beta are composed of 40-42 amino acids that are proteolytically produced from its
      precursor beta APP. We have shown that the deposition of A beta ending at the
      42nd residue (A beta 42) is one of the earliest pathological changes in AD
      brains. Genetic and cell biological evidence strongly suggests that mutations in
      beta APP or presenilin (PS) 1 and 2 genes cause AD through increase in production
      of A beta 42. Recently. PS1 and PS2 are shown to be the catalytic subunits of
      gamma-secretase that cleaves the intramembrane segments of beta APP and Notch.
      beta-amyloid hypothesis that emphasizes the primacy of A beta in the pathogenesis
      of AD is currently being verified by the new experimental therapeutic approaches,
      e.g., A beta vaccine therapy or administration of inhibitors of beta- or gamma
      secretases.

PMID- 12235838
TI  - [Noninvasive higher-order brain-function imaging by near-infrared spectroscopy].
AB  - The simultaneous position encoding method for optical topography was developed.
      Each channel has dual-wavelength optics to separately determine the changes in
      oxy-hemoglobin and deoxy-hemoglobin concentrations around their isobestic points
      at 805 nm. Part of the incident light penetrates the scalp and skull and is
      reflected from brain tissues including the cerebral cortex. Any change in the
      light extinction is mainly due to changes in the oxy-hemoglobin and/or the deoxy
      hemoglobin concentration during the activation of a functional area linked to a
      neuronal activity. Unlike conventional functional imaging methodologies, it can
      be used for behavioral studies because the flexible optical fibers allow a
      subject to move, and a very light and compact system can be made. Noninvasive
      dynamic optical topography has a wide variety of applications from basic science
      to clinical medicine. Several applications, such as the study of the Broca and
      Wernicke language areas, the assessment of the dominant hemisphere of the brain,
      epilepsy focus determination, and sleep studies are reported. We also tested a 14
      month-old baby with a extremely abnormal brain.

PMID- 12235839
TI  - [Recent advancements in MR functional analysis].
AB  - Recent advancements in magnetic resonance (MR) technology have revolutionized not
      only structural but also functional imaging. It is now possible to perform
      detailed analysis of all aspects of brain function non-invasively. From the
      neurological standpoint, analysis of gray matter can be categorized into (1)
      functional mapping and (2) neuron density measurement. Similarly, analysis of
      white matter can be categorized into (1) tract mapping and (2) axonal physiology.
      Corresponding techniques in MR imaging are functional MRI (fMRI), MR
      neuronography (MRN), MR tractography (MRT), and MR axonography (MRX). While fMRI
      is a T2* contrast based technique, the rest of the techniques are based on
      diffusion tensor analysis (DTA).

PMID- 12235840
TI  - [New trends in neuropathy practice: clinical approach to CIDP].
AB  - Our recent study showed that the overall prevalence of CIDP was estimated as 2.2
      per 100,000 population in Aomori Prefecture, in Northan Honshu of Japan. In our
      series of more than 80 cases with CIDP, a chronic acquired inflammatory
      demyelinating polyneuropathy, nearly 30% showed clear laterality of weakness, and
      electrophysiologic laterality or multifocality was apparent in almost all cases.
      Nearly 90% of patients were able to walk without walking aids or other
      assistance. Sixty% showed distal dominant muscular weakness. In 12 patients with
      age of onset under 15, pes cavus deformity was seen in 5. Two thirds complained
      numbness in the extremities during progressive phase. Four cases initially showed
      severe sensory ataxia associated with motor conduction block. It should be, thus,
      reminded that clinical spectrum of CIDP is enormously wide: chronic acquired
      demyelinating multiple mononeuropathy showing asymmetric involvement (Lewis
      Summer syndrome) should be put on one side of the clinical presentation of CIDP.
      Multifocal motor neuropathy (MMN) is, on the other hand, an unique syndrome
      mimicking amyotrophic lateral sclerosis (ALS). There may be, however, true
      association syndrome of CIDP and ALS presenting both peripheral nerve
      demyelination and pyramidal sign with progressive bulbar involvement. Recently,
      several atypical varieties of CIDP showing only one-limb involvement, upper limb
      weakness rather than lower limb power loss, or proximal weakness, etc ... have
      been reported in the literature. To realize such clinical variations of chronic
      acquired demyelinating neuropathy is important for early diagnosis and
      commencement of treatment of CIDP. Clinical guideline for suspicion of CIDP could
      be useful for general physicians and neurologists unfamiliar to peripheral
      neuropathies.

PMID- 12235841
TI  - [Recent therapeutic strategy for multiple sclerosis].
AB  - Multiple Sclerosis (MS) is an inflammatory demyelinating disease in the central
      nervous system (CNS), and it is clinically characterized by multiplicity in time
      (relapse and remission) and space (multiple lesions in CNS). In Asian countries
      including Japan, it has been pointed out that the prevalence rate of MS patients
      is extremely low and the frequency of the optic-spinal form of MS is high,
      compared with Western countries. Although the etiology remains unknown, it has
      been postulated that the pathogenesis of MS may involve immune mechanisms, virus
      like infectious agents or genetic factors. MS should be attacked on two fronts:
      treatment to suppress the disease itself and alter its natural history, and
      treatment to improve the symptoms of MS and mask the deficits it causes. Although
      steroid therapy probably improves MS attacks by inhibiting the immune system and
      reducing inflammation, they seem ineffective in changing the natural history of
      the disease or preventing ultimate disability. Interferon beta has been approved
      as an effective drug for reducing the rate of MS attacks and the volume of MRI
      lesions and altering its natural history, based on positive results from large
      controlled trials in western countries as well as in Japan. Other
      immunomodulating treatments, such as glatiramer acetate, intravenous
      immunoglobulin, and mitoxantorone have been also approved as effective drugs for
      MS.

PMID- 12235842
TI  - [Mite allergy and neural damage].
AB  - The number of adult patients with atopic disorders is increasing in Japan. We
      recently reported the occurrence of myelitis in patients with atopic diathesis
      (atopic myelitis). The characteristic features of myelitis with atopic diathesis
      are: (1) paresthesia/dysesthesia as the predominant symptom, (2) mild and
      infrequent, if any, muscle weakness, (3) preferential involvement of the cervical
      cord, (4) persistence of neurologic symptoms and MRI lesions, (5) hyperIgEaemia,
      (6) mite antigen-specific IgE in serum, and (7) normal cerebrospinal fluid
      findings. The spinal cord lesions show eosinophilic inflammation on biopsy. We
      also found an association of Hirayama disease, juvenile muscular atrophy of the
      distal upper limb, with atopic diathesis. In children, poliomyelitis-like illness
      following asthma attacks is well known as Hopkins syndrome. These three
      conditions suggest a link between atopic diathesis and the development of spinal
      cord disease.

PMID- 12235843
TI  - [Prion diseases, update].
AB  - In prion diseases, genotypic classification has been useful to understand the
      clinical course and pathological changes. However, among patients with the same
      prion protein (PrP) genotype, there are variations in the pathological and
      clinical phenotype. Recently, PrP typing was proposed by the molecular weight of
      protease-resistant PrP (PrPres). Combined with genotype and PrPres typing,
      sporadic Creutzfeldt-Jakob disease (CJD) could be classified precisely. In
      addition, we found the fragmented PrP molecules to differentiate between dura
      classic CJD and dura-plaque type CJD. We report herein that the fragmented PrP is
      a useful marker to classify human prion diseases, and also a clue to analyze
      abnormal PrP structures. The fragmented PrP was detected in patients with classic
      type CJD, sporadic thalamic-type CJD, familial CJD with codon 200 or 232
      mutation, or familial Gerstmann-Straussler syndrome (GSS) with codon 102
      mutation. Among patients with type-1 abnormal PrP, the transmission study was
      successful in sporadic CJD with type 1 PrPres and the fragment PrP, but not in
      CJD without the fragmented PrP. Thus, in the prion field, type-specific PrP
      structure contributes to the clinicopathology and transmissibility.

PMID- 12235844
TI  - [Channelopathy].
AB  - Recently, a variety of ion channel defects have been identified as the biological
      basis of certain familial epilepsies, paroxysmal movement disorders, myopathies
      and some degenerative disorders of central nervous system. Ion channel defects
      were mainly caused by genetic and autoimmune mechanisms. Here, we reviewed
      several channelopathies including spinocerebellar ataxia type 6, familial
      hemiplegic migraine, episodic ataxia type 2, familial hypokalemic periodic
      paralysis, congenital myotonia, malignant hyperthermia, epilepsy, Gitelman
      syndrome and Lambert-Eaton syndrome.

PMID- 12235845
TI  - [Microplate hybridization methods of reduced unspecific reassociation considering
      delta Tm--comparison between relative relatedness of DNA and key characters for
      Mycobacterium szulgai].
AB  - It has been recognized that colorimetric microdilution plate hybridization method
      (DDH) shows equivocal identification results for some strains of Mycobacterium
      gordonae, and that chemotaxonomic identification method reveals some intermediate
      pattern between Mycobacterium szulgai and M. gordonae. In the present study, the
      results obtained by chemotaxonomic identification method on 25 strains of M.
      szulgai were compared with those obtained by DDH method. In chemotaxonomic
      methods, 8 of 25 M. szulgai strains showed negative results on 14 days' tween80
      hydrolysis, 14 strains revealed negative nitrate reduction by the Tsukamura's
      method but all were positive by the Virtanen's method. Smooth colonies were found
      in 3 strains including M. szulgai type strain, JATA3201 (ATCC35799). Relative
      relatedness (relative color index) of genomic DNA was measured by DDH instead of
      spectrophotometric genomic DNA-DNA relatedness. A relative relatedness of 25 M.
      szulgai strains tested showed higher levels than 80%, but the inter-species
      relatedness to the other mycobacteria also showed high levels of 50-75%, when
      hybridizing temperature was set at 40 degrees C. At 56 degrees C, intra-species
      relative relatedness in 4 strains were lower than 50%, indicating that this
      condition is not appropriate. When hybridization temperature raised to 56 degrees
      C after overnight at 40 degrees C, a relative relatedness among 25 strains were
      again high (> 80%), and those to the other Mycobacterial species were lower than
      70%. When hybridized at 56 degrees C after overnight at 45 degrees C, an intra
      species relative relatedness again showed higher levels than 70% in all 25
      strains, and interspecies percentiles were lowered satisfactorily to < 25%. In
      conclusion, through avoiding reassociation of nonspecific DNA fragments during
      the hybridization process, 45 degrees C overnight followed by 56 degrees C
      hybridization (delta DDH method) was found to be the better condition for
      identification and classification of Mycobacterium szulgai.

PMID- 12235846
TI  - [Relative relatedness of 11 mycobacteria species by microplate hybridization
      methods considering delta Tm].
AB  - Intra-species variance within Mycobacterium xenopi, Mycobacterium gordonae or
      Mycobacterium szulgai has been reported in identification employing
      chemotaxonomic characteristics, 16 S rRNA gene sequences or relative relatedness
      (relative color index) of genomic DNA-DNA Hybridization. Genomic DNA-DNA
      reassociation at the constant temperature was found to be unreliable for
      classification of mycobacterial species. However, nonspecific DNA reassociation
      could be avoided by hybridization at 56 degrees C after 45 degrees C overnight,
      and this technique was named delta DDH method in the preceding paper. The present
      report shows relative relatedness (relative color index) of genomic DNA in delta
      DDH method among mycobacterial species. Relative relatedness was below 70% among
      BCG, M. kansasii, M. simiae, M. asiaticum, M. szulgai, M. gordonae, M. xenopi and
      M. nonchromogenicum. The results satisfied the criteria for bacterial
      classification, which was proposed by the International Committee for Systematic
      Bacteriology in 1987. In regard to Mycobacterium avium complex, relative
      relatedness between M. avium and M. intracellulare were approximately 75%. It
      appeared that M. avium and M. intracellulare could be classified into one
      species. It has been recognized, moreover, that there are intermediate strains
      between M. avium and M. intracellulare. Previously, numerical classification
      raised a concept of Mycobacterium avium-intracellulare-scrofulaceum complex. The
      present study revealed that relative relatedness of M. avium and of M.
      intracellulare to M. scrofulaceum were around 75%, while the percentiles of M.
      scrofulaceum relative to M. avium and that to M. intracellulare were both less
      than 50%. The relative relatedness of M. ulcerans against M. marinum was nearly
      65%, whereas the relative relatedness of M. marinum against M. ulcerans was
      approximately 90%. The data may be partly explained by the horizontal gene
      transfer mechanism.

PMID- 12235847
TI  - [Tuberculosis control in Kobe City--analyses of advisory contents and
      disqualified cases by integrated tuberculosis advisory committee].
AB  - The incidence of tuberculosis (TB) in Kobe City has been higher in comparison
      with that of Japan, thereby Kobe City ought to enforce anti-tuberculosis
      activities. Nine Wards public health departments of Kobe City used to convene
      their own tuberculosis advisory committees until April 1998, when a centralized
      committee was established to examine all TB patients. The new committee was
      authorized to issue clinical advice to registered physicians whenever necessary
      in order to improve treatment standard of TB. The author analyzed the contents of
      issued documents and observed any change in statistics before and after
      establishment of the committee. During the past 3 years, the new committee had
      sent 2,221 advisory documents to physicians, which occupied 35% of all 6,305
      applied cases. Main suggestions included proper choice of anti-tuberculosis
      agents, adequate duration of treatment and reference to the results of laboratory
      examinations. In addition, 140 cases were rejected for medical expenses subsidy
      by TB Law to avoid unnecessary long-term treatment. Main reasons of rejection
      were long-term treatment despite negative bacilli too more than one year,
      continuous single INH administration following the completion of the standard
      treatment and unnecessary treatment for the cases with inactive findings on chest
      X-ray. Since the establishment of the integrated committee, the statistics of TB
      has demonstrated a significant decrease in the incidence and the prevalence of TB
      with its annual reduction of 5.6, and 11.5 per 100,000 respectively. The
      proportion of bacteriologically confirmed cases among newly registered patients
      has increased, and the diagnostic accuracy was improved due to the decrease in
      the unknown bacteriology case. The proportion of the case treated by INH alone
      fall down rapidly and it is lower than that of the whole country. These data
      demonstrate that the integrated tuberculosis advisory committee contributes to
      standardize anti-tubercular treatment through dissemination of proper guidance on
      TB diagnosis and treatment to all medical facilities in the city.

PMID- 12235848
TI  - [A case of perforative peritonitis complicated with lung and intestinal severe
      tuberculosis].
AB  - A 27-year-old man was admitted to our hospital in September 18, 2000, complaining
      of fever, cough, appetite loss and body weight loss. He was diagnosed as advanced
      lung tuberculosis, because of chest X-ray findings and positive acid-fast bacilli
      in his sputum. He was administrated rifampicin (RFP), isoniazid (INH) and
      ethambutol (EB). Two days after starting treatment he complained of abdominal
      pain and the signs of perforating peritonitis. Emergency laparotomy was performed
      and we observed multiple ulcers and a perforation of ileum. We resected a part of
      distal ileum and ascending colon and made ileostomy. Histopathologic examination
      of resected ileum and colon showed multiple ulcers and epithelioid cell
      granulomas with caseous necrosis. Many acid bacilli were identified from the
      lesion by specially stained tissue sections. He was administrated streptomycin
      and INH by injection post-operatively while oral administration was impossible.
      Six days after the first operation, we found the signs of perforation in another
      part of the ileum. So we were obliged to perform second laparotomy and resect the
      part involved. Five days after the second operation, he was able to take RFP,
      INH, and levofloxacin per oral route. On February 8, 2001 we performed
      ileocolonal reconstruction with side to side anastomosis and closed ileostomy at
      the third laparotomy. He had continued chemotherapy and went back to Korea in
      April 7, 2001. Although intestinal tuberculosis has sharply declined in Japan
      thanks to development of effective antituberculous drugs, we should keep in mind
      that it could be a possible cause of the acute abdomen.

PMID- 12235849
TI  - [Chemotherapy with isoniazid and rifampicin for pulmonary tuberculosis].
AB  - Two-drug regimen of chemotherapy with isoniazid and rifampicin for pulmonary
      tuberculosis is the one of the standard methods of treatment for active pulmonary
      tuberculosis in Japan since 1996, while ATS/CDC and WHO/IUATLD recommended the
      three-drug or four-drug regimen containing chemotherapy pyrazinamide unless the
      prevalence of drug resistance, among new tuberculosis cases is low. We sent a
      questioners of 141 tuberculosis centers in Japan to investigate the rate of each
      standard chemotherapy regimen employed and reasons for selecting the two-drug
      regimen in each center. Of 3840 newly diagnosed cases in the 57 centers, 47.4%
      were treated with the four-drug regimen and 37.1% with the three-drug regimen,
      and two-drug regimen was employed in only 2.6%. Sputum smear-negative status was
      the major reason for selecting the two-drug regimen of chemotherapy. Though the
      two-drug regimen was used in few cases, taking into account the prevalence of
      primary resistance to isoniazid in Japan in 1997 was 4.4%, it was concluded to
      discontinue recommending the two-drug regimen as one of standard methods of
      treatment for pulmonary tuberculosis.

PMID- 12235850
TI  - [Prospects for development of new antituberculous drugs].
AB  - Tuberculosis (TB) is a growing international health concern, since it is the
      leading infectious cause of death in the world today. Moreover, the resurgence of
      TB in industrialized countries and the worldwide increase in the prevalence of
      Mycobacterium avium complex (MAC) infections in immunocompromised hosts have
      prompted the quest for new antimycobacterial drugs. In particular, the appearance
      of multidrug-resistant (MDR) strains of M. tuberculosis, which exhibit in vitro
      resistance to at least two major antituberculous drug (usually INH and RFP) and
      cause intractable TB, has greatly contributed to the increased incidence of TB.
      Because of the global health problems of TB, the increasing rate of MDR-TB and
      the high rate of a co-infection with HIV, the development of potent new
      antituberculous drugs without cross-resistance with known antimycobacterial
      agents is urgently needed. In this article, I reviewed the following areas.
      First, I briefly reviewed some new findings (mainly reported after 2000) on the
      pharmacological status of rifamycin derivatives (rifabutin, rifapentine, and
      rifalazil), fluoroquinolones (ciprofloxacin, ofloxacin, sparfloxacin,
      levofloxacin, gatifloxacin, sitafloxacin, moxifloxacin, and others), and new
      macrolides (clarithromycin, azithromycin, and roxithromycin). Second, I described
      other types of agents which are being developed as antimycobacterial drugs. Some
      of the agents discussed are already under preliminary clinical investigation, and
      others appear to be promising candidates for future development. In this review,
      the status of the development of new antimycobacterial, especially
      antituberculous agents including oxazolidinone (PNU-100480), 5'-nitroimidazole
      (CGI 17341), 2-pyridone (ABT-255), new riminophenazines, nitroimidazopyran (PA
      824), new ketolides (ABT-773, telithromycin) and defensins (human neutrophil
      peptide-I), was examined. Third, the development of new antitubercular drugs was
      discussed according to the potential pharmacological target. New critical
      information on the whole genome of M. tuberculosis recently elucidated and
      increasing knowledge on various mycobacterial virulence genes will promote the
      progression in the identification of genes that code for new drug targets. Using
      such findings on mycobacterial genomes, drug development using quantitative
      structure-activity relationship may be possible in the near future. In this
      review, I described the screening of drugs that have an inhibitory activity
      against dTDP-rhamnose synthesis of M. tuberculosis, as a new drug target of the
      organism. In addition, I discussed the usefulness of antisense oligo DNAs
      specific to mycobacterial genes encoding certain metabolic enzymes or virulence
      factors that play roles in the bacterial escape from antimicrobial mechanisms of
      host macrophages. Fourth, I reviewed the drug vehicles which enable efficacious
      drug delivery to their target in vivo. The usefulness of poly (DL-lactide-co
      glycolide) microsphere technology, which enables the encapsulated drugs to
      deliver the requested doses of them for prolonged time periods by a single shot
      without causing any toxicity and, moreover, enables the highly targeted delivery
      of the drugs to host macrophages, was discussed. Fifth, I described adjunctive
      immunotherapy for the management of patients with mycobacterial infections by
      giving certain immunomodulators in combination with antimycobacterial drugs.
      Adjuvant clinical trials using IL-2 or GM-CSF have been found to be efficacious
      to some extent in improving patients with tuberculosis or disseminated MAC
      infections. However, it seems that these immunopotentiating cytokines as well as
      IFN-gamma and IL-12 are not so promising for the therapeutic agents of
      mycobacterial infections because of the possible induction of immunosuppressive
      cytokines during adjuvant therapy and, in some cases, severe side-effect. Thus,
      the development of new classes of immuno-modulators other than cytokines,
      particularly those with no severe side-effect, is needed. This review dealt with
      ATP and its analogues which potentiate macrophage antimycobacterial activity via
      a purinergic P2X7 receptor. Finally, I described the roles of type II alveolar
      epithelial cells in the establishment of mycobacterial infections in the host
      lungs and the profiles of drug susceptibilities of M. tuberculosis and MAC
      organisms replicating within the type II pneumocytes. These findings are useful
      to precisely assess or predict the in vivo therapeutic activity of a given
      antimycobacterial drug from its in vitro activity. In this article, I have
      thoroughly reviewed the status of the development of new antimycobacterial drugs.
      There are a number of difficulties in the drug-design for the development of new
      drug formulations with increased potential for antimycobacterial effects,
      excellent pharmacokinetics, and tolerability. It should be emphasized that the
      most urgent goal of chemotherapy of tuberculosis and MAC infections, especially
      that associated with HIV infection, is to develop highly active, low-cost drugs
      which can be used not only in industrialized countries but also in developing
      countries, since the incidences of AIDS-associated intractable tuberculosis is
      rapidly increasing in the latter.

PMID- 12235851
TI  - Study on the roles of cytokines involved in mycobacterial infection.
AB  - The roles of various cytokines in early-phase mycobacterial infection were
      investigated utilizing murine tuberculosis models. Among them, IFN-gamma and TNF
      alpha are very important in protective immunity against mycobacterial infection.
      This finding is closely associated with human tuberculosis. It is reported that
      persons with IFN-gamma receptor 1 deficiency and patients with rheumatoid
      arthritis and Crohn's disease are susceptible to Mycobacterium tuberculosis. It
      is expected that a novel immunotherapy and a diagnostic method of tuberculosis
      are developed by clarifying roles of various cytokines immunologically in early
      phase mycobacterial infection.

PMID- 12235852
TI  - [The transport mechanism of polycationic compounds across intestinal and renal
      cell membrane].
AB  - This article reviewed the transport mechanism of polycationic compounds across
      rat intestinal and renal cell membranes. The inside-negative diffusion potential
      stimulated the initial uptake of dicationic compounds into intestinal brush
      border membrane vesicles, and a good correlation was observed between
      lipophilicity and the amount of diffusion potential-dependent transport of the
      dications. On the other hand, tri- and tetracationic compounds were not affected
      by the diffusion potential because of their much lower lipophilicity. The
      membrane surface potential affected to the transport of polycationic compounds,
      similar to monocationic compounds. Therefore it appears that the membrane surface
      potential plays a common role in the transport of mono- and polycationic
      compounds across cell membranes. On the intestinal basolateral membrane, it was
      found that there was a Na+/putrescine symporter. This recognized dicationic
      compounds and transported them from the blood into intestinal cells. This
      transporter did not recognize spermine and spermidine. Furthermore, we found a
      novel transport system, a Na+/spermine antiporter, on the rat renal brush-border
      membrane. This transporter recognized aliphatic polycation, which has more than
      four amino groups, and actively secreted spermine and trientine into the renal
      proximal tubules in vitro and in vivo. However, this transporter did not
      recognize trientine-copper complex. These results are useful for the prediction
      of the intestinal absorption and renal excretion of polyamine derivatives.

PMID- 12235853
TI  - [Structures and functions of the 26S proteasome Rpn10 family].
AB  - The ubiquitin-dependent proteolytic pathway is thought to be one of the vital
      systems for cellular regulations, including control of the cell cycle,
      differentiation and apoptosis. In this pathway, poly-ubiquitinated proteins are
      selectively degraded by the 26S proteasome, a multisubunit proteolytic machinery.
      Recognition of the poly-ubiquitin chain by the 26S proteasome should be a key
      step leading to the selective degradation of target proteins, and the Rpn10
      subunit of the 26S proteasome has been shown to preferentially bind the poly
      ubiquitin chain in vitro. We previously reported that the mouse Rpn10 mRNA family
      is generated from a single gene by developmentally regulated, alternative
      splicing. To determine whether such alternative splicing mechanisms occur in
      organisms other than the mouse, we searched for Rpn10 isoforms in various
      species. Here we summarize the gene organization of the Rpn10 in lower species
      and provide evidence that the competence for generating all distinct forms of
      Rpn10 alternative splicing has expanded through evolution. Some of the Rpn10
      family genes were found to be expressed in distinct developmental stages,
      suggesting that they have distinct functions during embryogenesis. For example,
      Rpn10c and Rpn10e were exclusively expressed at specific developmental stages and
      in specific tissues, while Rpn10a was expressed constitutively. Our experimental
      results indicate that the respective Rpn10 proteins possess distinct roles in the
      progression of development. Furthermore, some of the Rpn10 variants specifically
      interacted with important developmental regulators.

PMID- 12235854
TI  - [Study on the effectiveness of rapid and simple methods for analysis of
      pesticides causing acute poisoning in emergency medicine].
AB  - Quick detection of substances causing acute poisoning is often difficult. There
      is a need for methods that allow rapid detection of pesticides causing acute
      poisoning, which is often severe and has a high mortality rate, for quick
      diagnosis and appropriate treatment. The aim of this study was therefore to
      develop rapid and simple analytical methods for detecting acute poisoning
      inducing substances in samples of stomach contents, returned gastric lavage
      solution, serum, or urine using an analytical device that can be used in the
      field as well as in pharmaceutical divisions and emergency medical units. We
      first examined the effectiveness of a screening method using TLC and then the
      effectiveness of HPLC equipped with a photo-diode array detector (HPLC-DAD) for
      qualitative and quantitative measurements. In the former technique, we were able
      to develop a rapid and simple screening method by adjusting the TLC plate and
      development solvent. In the latter technique, we were able to establish rapid and
      accurate methods for qualitative and quantitative measurements by using a column
      switching technique in which a sample is injected directly into the column
      without pretreatment. Results of tests using actual samples obtained from
      patients with acute poisoning showed that the time required for detection using
      these techniques (less than 1 h) was much shorter than that required using
      conventional techniques. The use of these techniques should reduce the mortality
      rate in cases of acute poisoning, since physicians would be able to receive
      prompt advice regarding diagnosis, prognosis, and treatment methods. We have also
      designed a practical system for analysis of acute poisoning-inducing pesticides.

PMID- 12235855
TI  - [Functional molecules in allergic bronchial asthma].
AB  - Bronchial asthma is considered to be a chronic airway inflammatory disease,
      characterized by airway obstruction, airway eosinophilic inflammation, and airway
      hyperresponsiveness (AHR) to a variety of stimuli. AHR is thought to be an
      important symptom, because the severity of the disease is generally correlated
      with the degree of AHR. Recent clinical studies have demonstrated the involvement
      of airway inflammation in the development of allergen-induced AHR, although, the
      mechanism of allergen-induced AHR has not been fully elucidated and remains
      controversial. In vivo animal models might provide important information on this
      point. We have established a mouse model of allergic asthma, which is
      characterized by airway eosinophilia, IgE production, T helper type 2 (Th2)
      cytokine production in the airway, and AHR, and investigated the role of
      inflammatory cells and functional molecules. Results from gene-knockout and
      mutant mice demonstrated the involvement of T cells, mast cells, prostanoids, and
      Th2 cytokines including interleukin (IL)-4 and IL-5 in the development of
      allergen-induced airway inflammation and AHR. In contrast, treatment with anti-IL
      4 monoclonal antibody (mAb) or anti-IL-5 mAb during allergen inhalation did not
      inhibit allergen-induced AHR, although the combination of these mAbs clearly
      inhibited the enhanced responsiveness. These data indicate that it is a better
      strategy for control of the disease to inhibit or suppress multifunctional
      molecules like corticosteroids rather than to inhibit a single factor, because
      bronchial asthma is a multifactorial disease.

PMID- 12235856
TI  - [Possible role of a neuropeptide PACAP (pituitary adenylate cyclase-activating
      polypeptide) on stimulus-secretion coupling in catecholamine neuron].
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide
      first isolated from ovine hypothalamic tissue. This peptide stimulates adenylate
      cyclase activation. However, few details were known of the function of this
      peptide on stimulus-secretion coupling in neuronal cells. The authors have
      investigated the role of PACAP on catecholamine biosynthesis and secretion using
      cultured bovine adrenal chromaffin cells as a model for catecholamine-containing
      neurons. PACAP38, the 38-amino acid form of PACAP, increased cAMP formation in
      bovine adrenal chromaffin cells. In addition, PACAP38 increased [Ca2+]i
      associated with PI turnover and Ca2+ influx into the cells. The synthesis of
      catecholamine and the phosphorylation of tyrosine hydroxylase, a rate-limiting
      enzyme of catecholamine biosynthesis, stimulated by the maximal effective
      concentration of dibutyryl cAMP or a high concentration (56 mM) of K+ were
      further enhanced by PACAP38. Thus PACAP38 stimulated the pathway of catecholamine
      biosynthesis mainly by both activation of cAMP- and Ca2(+)-dependent protein
      kinases. On catecholamine secretion from the cells, the effect of PACAP38 was
      markedly potentiated by addition of ouabain, an inhibitor of Na+/K+ ATPase. This
      markedly potentiated secretion was greatly reduced with Na+ omitted-sucrose
      medium. PACAP38 increased 22Na+ influx into the cells treated with ouabain. Thus
      PACAP38 with ouabain stimulated catecholamine secretion by accumulation of
      intracellular Na+, resulting in an increase in Ca2+ influx. These results
      indicate that the neuropeptide PACAP has an important role in stimulus-secretion
      coupling in adrenal chromaffin cells.

PMID- 12235857
TI  - [New antifungal antibiotics, bacillopeptins and fusaricidins].
AB  - We isolated four strains of bacteria producing antifungal antibiotics from the
      rhizosphere of garlic with basal rot caused by the plant pathogenic fungal strain
      Fusarium oxysporum. Among them, Bacillus subtilis FR-2 was found to produce new
      antifungal antibiotics, named bacillopeptins A, B, and C. Their structures have
      been determined by 1D and 2D NMR and MS experiments, and amino acid analysis
      coupled with chiral HPLC, to be cyclic lipopeptides each containing a long-chain
      beta-amino acid. Another bacterial strain, Bacillus polymyxa KT-8, was shown to
      produce new antifungal antibiotics named fusaricidins A, B, C, and D which are
      more potent than bacillopeptins in their antimicrobial activity. The structures
      of the fusaricidins have been elucidated similarly as bacillopeptins to be cyclic
      hexadepsipeptides all containing 15-guanidino-3-hydroxypentadecanoic acid as a
      side chain. Fusaricidins strongly inhibit the growth of various kinds of fungi
      and moreover surprisingly show strong inhibitory activity against Gram-positive
      bacteria such as Staphylococcus aureus or Micrococcus luteus.

PMID- 12235858
TI  - [Enhancing effects of ion-pair complexes on skin permeation of cromolyn in
      vitro].
AB  - Lipophilic ion-pair complexes of 3-dl-alpha-tocopherylcarbonyl-1-n-alkyl
      pyridinium-cromolyn (TAP-CG) were designed to enhance the percutaneous absorption
      of cromolyn (CG), and the effect of n-alkyl chainlength of the ion-pair complexes
      on the CG permeation through hairless mouse skin was evaluated in vitro. The
      permeation rates of CG were examined in isopropyl myristate (IPM) suspension
      using static Keshany-Chien type diffusion cells at 32 degrees C. The permeation
      parameters, steady-state flux, diffusion coefficient, partition coefficient
      between skin and IPM, and permeability coefficient were determined. Steady-state
      fluxes of CG increased linearly with the increasing n-alkyl chain-length of TAP
      CG, and 3-dl-alpha-tocopherylcarbonyl-1-n-hexyl-pyridinium-cromolyn (THP-CG)
      produced the highest CG flux (0.62 +/- 0.11 nmol.cm-2.h-1), which was 14-fold
      greater than that of CG.Na in IPM suspension and more than 480-fold greater than
      that of CG.Na in aqueous solution due to increasing lipophilicity. In the case of
      TAP-CG with longer n-alkyl chainlength than THP-CG, however, the steady-state
      fluxes of CG decreased due to the high molecular weight and/or the high
      lipophilicity of the ion-pair complexes. It is suggested that lipophilic ion-pair
      complexes, especially THP-CG, are effective in absorption of cromoglicate through
      the skin. The results would be useful for studies on the role of each counterion
      in the lipophilic ion-pair complexes.

PMID- 12235859
TI  - [Estimation of adverse drug reactions by the evaluation scores of subjective
      symptoms (complaints) and background of patients--VI. Drug-induced metabolic
      disorders].
AB  - OBJECTIVES: The purpose of this study was to develop, implement, and assess
      estimation procedures to prevent adverse drug reactions (ADRs), especially drug
      induced metabolic disorders, based on the subjective symptoms (complaints) of
      patients. METHODS: Our own database called CARPIS (Case Reports of Adverse Drug
      Reaction and Poisoning Information System) was started in 1987 and now contains
      ca. 23,000 case reports of ADRs. We extracted 264 cases of drug-induced metabolic
      disorders from CARPIS, such as hyperglycemia, hypoglycemia, and hypokalemia.
      Evaluation scores were created based on the subjective symptoms and the
      backgrounds of these patients. The scores were applied to the 264 cases to
      demonstrate their efficiency in estimation of ADRs. RESULTS: The evaluation
      scores estimated ADRs as follows: 39.6% of the 96 hyperglycemia cases, 53.6% of
      the 84 hypoglycemia cases, and 59.5% of the 84 hypokalemia cases. The validity
      measures of the evaluation scores were estimated to be as follows: for
      hyperglycemia sensitivity (SE) = 39.6%, specificity (SP) = 99.0%, predictive
      value of positive test (PVP) = 97.4%, positive likelihood ratio (PLR) = 39.6, and
      negative likelihood ratio (NLR) = 0.61; for hypoglycemia, SE = 53.6%, SP = 93.0%,
      PVP = 86.5%, PLR = 7.7 and NLR = 0.50; and for hypokalemia, SE = 59.5%, SP =
      99.0%, PVP = 98.0%, PLR = 59.5, and NLR = 0.41. CONCLUSIONS: The proposed
      evaluation scores are a reliable estimation method to detect ADRs related to drug
      induced metabolic disorders. The scores should be incorporated into the
      integrated ADR estimation system available at a Web site our institution is
      developing, along with other evaluation scores of drug-induced liver disorders,
      extrapyramidal symptoms, and leakopenia, and druy eruptions.

PMID- 12235860
TI  - [Combination use of kampo-medicines and drugs affecting intestinal bacterial
      flora].
AB  - The intestinal bacteria, Eubacterium sp. and Bifidobacterium sp., participate in
      the metabolism of active kampo-ingredients, glycyrrhizin (GL), sennoside (SEN)
      and baicalin (BL). Since antibiotics and bacterial preparations, Bifidobacterium
      longum (LAC-B), Clostridium butyricum (MIYA-BM), and Streptococcus faecalis
      (BIOFERMIN), affect the bacterial population in intestinal bacterial flora,
      metabolism of the active kampo-ingredients in the bacterial flora may be altered
      by their combined administration. We investigated 1199 prescriptions including
      kampo-medicines for 308 patients. Combination use of kampo-medicines with
      antibiotics and bacterial preparations occurred with 7% and 10% of the kampo
      prescription, respectively. Most antibiotics have activity against intestinal
      bacteria, except that cephems and macrolides are not active against to E. coli.
      This means that antibiotics may lower the metabolism of GL, SEN and BL when
      administered in combination. On the other hand, it is also highly possible that
      bacterial preparations increase the number of Eubacterium sp. and Bifidobacterium
      sp., resulting in enhanced metabolism of GL and SEN when they are used
      concomitantly with kampo-medicines. The present results suggested that the drug
      interactions of kampo-medicines with antibiotics and bacterial preparations
      should be confirmed in clinical studies.

PMID- 12235861
TI  - Microbial growth-promotion activity of 3-hydroxymonoazine- and N-hydroxydiazine
      type heterocycles.
AB  - Three 3-hydroxymonoazine- and three N-hydroxydiazine-type heterocycles were
      tested whether they act as artificial siderophores toward Aureobacterium
      flavescens JG-9 (ATCC No. 25091). Among them, 1-hydroxy-3,5,6-trimethyl-2(1H)
      pyrazinone (3) showed the highest growth-promotion activity comparable to
      desferrioxamine B (DFB), a natural trihydroxamate siderophore, at 48.5 microM or
      above, followed by 1-hydroxy-5,6-dimethyl-2(1H)-pyrazinone (2), 1-hydroxy-4,6
      dimethyl-2(1H)-pyrimidinone (1), and 3-hydroxy-2-methyl-1-phenyl-4(1H)-pyridinone
      (6), while 3-hydroxy-1,2-dimethyl-4(1H)-pyridinone (5) did not show the
      bioactivity. These results are the first examples of N-hydroxydiazine-type
      heterocycles acting as artificial siderophores for A. flavescens JG-9.

PMID- 12235862
TI  - [Neuroradiological findings of relatively rare tumors of the brain].
AB  - In the publication by the World Health Organization of the histological
      classification of central nervous system tumors in 1993, several new tumor types
      were added, including pleomorphic xanthoastrocytoma (PXA), dysembryo-plastic
      neuroepithelial tumor (DNT), and desmoplastic infantile ganglioglioma (DIG).
      Referring to these newly classified tumors of the brain, the present article
      describes the neuroradiological findings of relatively rare tumors of the brain
      such as PXA, subependymoma, gangliocytoma, dysplastic cerebellar gangliocytoma
      (Lhermitte-Duclos disease), DIG, central neurocytoma (CN), neuroblastoma,
      desmoplastic medulloblastoma, atypical teratoid/rhabdoid tumor (ATRT),
      glossopharyngeal schwannoma, and malignant fibrous histiocytoma (MFH). PXA and
      DIG affect the cerebral hemisphere and appear to be cystic masses with a solid
      component on CT and MRI. Gangliocytomas commonly occur in the floor of the third
      ventricle and the temporal lobe. CT and MRI typically show a mass lesion with no
      vasogenic edema. In Lhermitte-Duclos disease, T2-weighted MR images reveal
      characteristic enlarged folia. Desmoplastic medulloblastomas tend to favor the
      cerebral hemisphere in the adolescent. ATRTs are rarely seen in infants or
      children and resemble medulloblastomas or primitive neuroectodermal tumors.
      Intracranial MFHs are also rare tumors and sometimes resemble the meningiomas.

PMID- 12235863
TI  - [MRI of the female pelvis: useful information for daily practice].
AB  - The MR findings of non-neoplastic gynecologic diseases were comprehensively
      reviewed. Pelvic inflammatory disease is a common benign disease affecting
      reproductive women, in which imaging findings are similar to those of malignant
      tumors of the adnexa. Torsion or rupture of benign ovarian masses can also mimic
      malignant ovarian tumors. Diagnostic keys to these conditions are presented in
      this review. The usefulness of dynamic contrast MRI in diagnosing ectopic
      pregnancy is also indicated. Placenta accreta is a catastrophic condition that
      occurs from labor to the postpartum period. Preliminary results of the diagnostic
      significance of dynamic contrast MRI in differentiating retained placenta accreta
      and normally attached placenta are also presented. Eclampsia is defined as
      convulsion complicated with pregnancy and is demonstrated as posterior reversible
      encephalopathy syndrome on imaging. Some commentary on eclampsia is given
      together with characteristic MR imaging findings.

PMID- 12235864
TI  - [Chemoradiotherapy for lung, esophageal, and uterine cervix cancer].
AB  - Some early cancer is completely cured by radiation therapy alone. In many
      advanced cases, however, local control rates are low with radiation therapy.
      Chemoradiotherapy has recently become a standard treatment to improve therapeutic
      results. The objective of chemoradiotherapy is to improve local tumor control, to
      control potential systemic metastases, or both. In chemoradiotherapy, drugs
      effective against primary tumors are selected, platinum compounds often being key
      drugs. Regarding the timing of radiation and chemotherapy, three patterns are
      possible: sequential, concurrent, and alternating. In the sequential pattern, the
      severity of acute toxicity decreases; however, an extended total therapeutic
      period can lower the antitumor effect. In the concurrent pattern, the maximum
      antitumor effect is expected because of the simultaneous action of radiation and
      chemotherapy, but the severity of acute toxicity is intensified to the extent
      that treatment withdrawal or dose reduction may be required. In the alternating
      pattern, radiation therapy is quit transiently during chemotherapy. As a result,
      the irradiation period is extended so that the antitumor effect might be reduced.
      To explore the methods and results of chemoradiotherapy in each disease, this
      paper also reports on the results of meta-analysis and randomized trials.
      Although chemoradiotherapy is not recommended for all patients, it is considered
      to be more appropriate than radiation therapy alone in patients who have good
      performance status and adequate organ function.

PMID- 12235865
TI  - [RadGenomics project].
AB  - Human health conditions are largely determined by a complex interplay among
      genetic susceptibility, environmental factors, and aging. The RadGenomics
      project, which began in April 2001, promotes analysis of genes in response to
      irradiation, identification of their allelic variants in the human population,
      development of an effective procedure for quantitating individual radio
      sensitivity, and analysis of the interrelationship between genetic heterogeneity
      and susceptibility to irradiation. Major groups of genes with which the project
      will concern itself include DNA repair genes, cell cycle genes, oncogenes, tumor
      suppressor genes, genes for programmed cell death, genes for signal transduction,
      and genes for oxidative processes. The outcome of the RadGenomics project should
      lead to improved protocols for personalized radiotherapy and reduce the possible
      side effects of treatment. The project will contribute to future research on the
      molecular mechanisms of radiation sensitivity in humans and stimulate the
      development of new high-throughput technology for a broader application of the
      biological and medical sciences. Identification of functionally important
      polymorphisms in the radiation response genes may determine individual
      differences in sensitivity to radiation exposure. The staff members, who are
      specialists in a variety of fields including genome science, radiation biology,
      medical science, molecular biology, and bioinformatics, have come to the
      RadGenomics project from various universities, companies, and research
      institutes.

PMID- 12235866
TI  - [Single breath-hold three-dimensional MR coronary angiography with true FISP].
AB  - Single breath-hold MR coronary angiography with three-dimensional (3D) true FISP
      was performed in 6 volunteers. Every scan was performed in a single breath-hold,
      and no contrast material was used. The length of visualized vessels was 12.2 +/-
      1.2 cm for the RCA and 6.6 +/- 1.1 cm for the LAD. The signal-to-noise ratio and
      contrast-to-noise ratio were 22.8 +/- 6.8 and 17.5 +/- 7.1, respectively. MR
      coronary angiography with 3D true FISP has the potential to obtain good coronary
      angiograms for the screening of coronary artery disease.

PMID- 12235867
TI  - Confocal laser microscopy of chondrocytes that received gene transfer using in
      vitro electroporation.
AB  - To develop a gene therapy for osteopathies, this study was conducted to establish
      a method of transferring the BMP gene, a bone formation factor, to cells and
      administering the cells with BMP expression to patients with osteopathies.
      Although virus vectors are frequently used for gene transfer, there has been
      reported a death case of gene therapy using the adenovirus vector. Therefore,
      various efforts have been made to prevent such complications. In the present
      study, we used electroporation by which gene transfer can be efficiently
      performed without inducing severe complications after electric perforation of the
      cell membrane. Human bone tissues were initially collected intraoperatively, and
      BMP-2 and Smad4 genes were cloned and integrated into GFP and DsRed plasmid
      vectors. Using in vitro electroporation, these plasmid vectors were transferred
      to the cultured chondrocytes (KTN-1) derived from human herniated intervertebral
      disk. Confocal laser microscopy revealed that the BMP gene was successfully
      transferred to the nucleus of chondrocytes in the presence of Smad. Since
      electroporation facilitated human gene transfer to the target cells, gene therapy
      using electroporation may facilitate individualized treatment for patients.

PMID- 12235868
TI  - Effects of fluid percussion injury on the neuronal activity in the hippocampal
      CA1 area and the dentate gyrus of the rat.
AB  - The effect of fluid percussion injury (FPI) on the propagation of neuronal
      activity in the rat hippocampus was investigated by using optical and
      extracellular recording techniques. Under anesthesia with pentobarbital sodium, a
      moderate impact (1.5-2.0 atm) was applied to the parietal cerebral cortex of the
      left hemisphere at -3 mm (i.e. caudal) from bregma, 3.5 mm lateral from the
      sagittal suture. Systemic oxygenation remained normal during the anesthesia. The
      rats recovered fully from anesthesia within 30-60 min, and their subsequent
      behavior, such as feeding and grooming, was normal. After a survival period of 1
      week from the FPI or sham-operation, neuronal activities were recorded from the
      hippocampal CA1 region and the dentate gyrus (DG) in either coronal or horizontal
      brain slice preparations. In sham-operated rats, there was no significant
      difference in the neuronal activity between contralateral and ipsilateral
      hippocampal CA1 areas and DG. In coronal slices (-5.6(-)-6.4 mm from bregma),
      moderate impact (1.5-2.0 atm) markedly depressed the neuronal activity of the
      ipsilateral (impact side) CA1 region and of the DG directly under the cerebral
      cortex that received the impact. In horizontal slices, on the other hand, the
      neuronal activity was markedly enhanced in the ipsilateral hippocampal CA1 region
      and the DG adjacent the temporal lobe of the cerebral cortex. Field potentials
      were recorded from the dentate granule cell layer and the hippocampal CA1
      pyramidal cell layer in either coronal or horizontal slice. Moderate impact
      strongly depressed the field potential in the ipsilateral CA1 region and DG
      directly under the injured cerebral cortex. In horizontal slices, the field
      potential was followed by multiple population spikes in ipsilateral hippocampal
      CA1 and the DG neurons. Bicuculline (15 microM) increased the number of spikes of
      the field potential even after the brain injury. These results suggest that FPI
      depresses the neuronal activity in the ipsilateral hippocampus directly under the
      injured parietal cortex, while it enhances the neuronal activity of the
      ipsilateral hippocampus adjacent to the temporal cortex. The facilitation of
      neuronal activity following FPI is not due to disinhibition resulting from
      depression of GABAergic interneuron activity.

PMID- 12235869
TI  - Experimental studies on the effects of the combined use of N-(4
      hydroxyphenyl)retinamide (4-HPR) and tamoxifen (TAM) for estrogen receptor (ER)
      negative breast cancer.
AB  - We investigated the effects of combination therapy with N-(4
      hydroxyphenyl)retinamide (4-HPR) and tamoxifen (TAM) on estrogen receptor (ER)
      negative breast cancer, for which no effective supplementary therapy has been
      established, using the human breast cancer cell line MDA-MB-231. TAM or 4-HPR
      alone had little antitumor effect, but the combined use of TAM and 4-HPR had a
      strong cell growth inhibitory effect. Cell cycle analysis by flow cytometry
      showed an increased frequency of the G2/M phases in the 4-HPR-TAM combination
      group. Measurement of 3H-TAM incorporation into the cell showed that, compared
      with the TAM group, the 4-HPR-TAM combination group incorporated about 1.45 times
      more TAM into the cell. Thin-layer chromatographic analysis of changes in the
      cell membrane ganglioside GM3 showed a marked increase in GM3 in the 4-HPR-TAM
      combination group. We speculate that the administration of TAM in the presence of
      4-HPR changes the membrane glycolipid GM3, increasing intracellular TAM
      concentrations, thus exerting antitumor activity. Presumably, during this
      process, antitumor effects do not induce cell death but arrest the cell cycle in
      the G2 phase. Thus, the combined use of TAM and 4-HPR inhibited the growth of the
      ER-negative breast cancer cell line MDA-MB-231. These results suggest that
      combination therapy with TAM and 4-HPR can be a potent supplementary therapy also
      for ER-negative patients in clinical practice.

PMID- 12235870
TI  - Treatment of secondary spontaneous pneumothorax complicating silicosis and
      progressive massive fibrosis.
AB  - To clarify the management and treatment for the refractory cases of secondary
      spontaneous pneumothorax (SSP), we analyzed the clinical features in SSP
      complicating three cases of advanced silicosis, and discussed the available
      treatment. All three cases were males of age ranging from 60 to 70 years, and had
      silicosis with massive progressive fibrosis (PMF), classified as type 4 (PR4)
      according to the ILO guidelines. There was no correlation between the onset of
      SSP and the smoking habit, or the duration of the occupational exposure to
      silica. In a total of ten episodes of SSP, a refractory episode occurred in each
      of the three patients. No surgical treatment was possible because of some
      complications. Therefore, we administered conservative treatments under
      mechanical ventilation. The conservative treatments used were tube drainage with
      suction in each episode and pleurodesis by the combination of minocycline and OK
      432 in one case. Approximately one month was the average time required for the
      air leak cessation. A significant decline in arterial oxygen tension (PaO2) was
      observed after the treatment of one case, suggesting further respiratory
      deterioration. These results imply that the more aggressive treatments for
      refractory SSP should be limited because of the patient status and progression.
      More information might be required before performing these options safely and
      effectively.

PMID- 12235871
TI  - Surgical treatment for chronic pancreatitis: results of pancreatic duct drainage
      operation and pancreatic resection.
AB  - Between 1978 and 1999, 86 patients with chronic pancreatitis were surgically
      treated at the Surgical Department of Kurume University Hospital. Of these
      patients, 30 were treated by pancreatic duct drainage operation (drainage
      operation), while 40 were treated by pancreatic resection, and the results were
      compared between the two groups. In patients who underwent drainage operation,
      pain disappeared in 85.7%, slightly relieved in 10.7%, and not relieved in 3.6%.
      In patients who underwent pancreatic resection, pain disappeared in 73.4%,
      slightly relieved in 13.3%, and not relieved in 13.3%. Therefore, there was no
      significant difference in the pain-relieving effect between the two groups.
      However, the pain-relieving effect was poorer in patients who underwent
      pancreatic resection than in those who underwent drainage operation. In addition,
      all patients who showed poor results for pain relief had alcoholic pancreatitis.
      Endocrine and exocrine functions of the pancreas were improved in 6, maintained
      in 2, and exacerbated in 4 patients who underwent drainage operation. In patients
      who underwent pancreatic resection, endocrine and exocrine function of the
      pancreas were improved in 3, maintained in 3, and exacerbated in 13. Therefore,
      endocrine and exocrine function of the pancreas were poorer in patients who
      underwent pancreatic resection than in those who underwent drainage operation.
      Distant results in patients who underwent drainage operation were good in 75.0%,
      fair in 15.0%, and poor in 10.0%. In patients who underwent pancreatic resection,
      distant results were good in 80.0%, fair in 13.3%, and poor in 6.7%. Therefore,
      favorable distant results were obtained in both groups. These findings suggest
      that surgical techniques that preserve functions of the pancreas should be
      selected during surgical treatment for chronic pancreatitis. We consider that the
      presence or absence of main pancreatic duct dilation and the site of pancreatic
      lesions are important indices for selecting surgical techniques. Therefore,
      drainage operation consisting of pancreaticojejunostomy should be indicated for
      patients with main pancreatic duct dilation, while pancreatic resection should be
      indicated for those without main pancreatic duct dilation, those with localized
      pancreatic lesions, and those with suspected pancreatic cancer.

PMID- 12235872
TI  - Evolution of virtual CT laparoscopy for preoperative imaging in laparoscopic
      cholecystectomy.
AB  - The purpose of this study was to determine the feasibility of virtual endoscopy,
      named as "virtual CT laparoscopy", in the hepatobiliary system prior to
      laparoscopic cholecystectomy. We applied this technique to 28 patients suspected
      of having biliary disease. These images were compared and analyzed qualitatively
      based on visualization of the structures critical to operative cholangiography
      and surgical findings. Twenty-four patients, who underwent laparoscopic
      cholecystectomy, were evaluated as follows: the common bile duct and the hepatic
      duct were adequately visualized in 23 (96%) of the 24 patients, the cystic duct
      in 21 (88%), the gallbladder opacification in 20 (83%), the liver inferior
      surface in 20 (83%). Four patients had anatomic variations detected virtual CT
      laparoscopy and were proven by operative cholangiography and surgical findings.
      We emphasize that our new technique may contribute to the laparoscopy during
      surgery as the aid of understanding of anatomical structures in these organs.

PMID- 12235873
TI  - A patient with advanced gastric cancer, underwent curative gastrectomy and
      partial resection of metachronous hepatic metastases, is surviving for 13 years
      to date.
AB  - We have reported a successful case of curative partial liver resection of
      metachronous liver metastasis from advanced gastric cancer. The patient was 56
      years old and has undergone total gastrectomy with D2 lymph node dissection (2
      type, well-differentiated adenocarcinoma, H0P0n0se, Stage 2). At 18 months later,
      follow-up ultrasound detected liver metastasis in the right posterior segment.
      Together with other imaging modalities, it was diagnosed as a solitary lesion
      without any other recurrence, and we performed partial resection of the right
      posterior segment. During the operation, there was no sign of any other
      recurrence (no peritoneal dissemination, no lymph node metastasis, and no other
      liver metastasis). Two Mitomycin-C (MMC) intravenous injections were given as
      postoperative chemotherapy. Usually, surgery for liver metastasis from gastric
      cancer is very rare as a curative therapy, because it is difficult to predict the
      effectiveness of the operation. In the present case, we decided on the operation
      since there was no sign of any other recurrence. It has now been 13 years to date
      since the partial liver resection and the patient remains free from recurrence.

PMID- 12235874
TI  - Combined fractures in the capitellum and the radial head associated with medial
      capsular avulsion.
AB  - We present a case with an unusual fracture. A 28-year-old man presented a painful
      and swollen left elbow after falling down. Radiographs revealed combined
      fractures in the capitellum and the radial head associated with a medial capsular
      avulsion. Two osteochondral fragments from the capitellum were found at the
      operation. One was the free fragment revealed on radiographic examination.
      Another was not revealed before the operation and was found piercing the fracture
      line of the radial head. These two fragments were removed. The radial head
      fracture was reduced and was fixed using two Herbert screws. It is very difficult
      to detect a fragment of the capitellum that impaled the radial head on a plain
      radiogram before operation. Also, a capsular injury and/or ligamentous injury is
      often overlooked. This fact should be kept in mind whenever a non-operatively
      treated radial head fracture fails to respond as expected.

PMID- 12235875
TI  - A case of gallbladder cancer associated with pancreaticobiliary maljunction.
AB  - We report a case of gallbladder cancer associated with pancreaticobiliary
      maljunction. The patient was a 60-year-old woman who consulted a local doctor
      because of discomfort in the right hypochondriac region. Abdominal
      ultrasonography (US) showed a gallbladder abnormality, and she was referred to
      Kurume University Hospital, where she was hospitalized for further study and
      surgery. Abdominal US revealed a sessile tumor with an irregular surface in the
      fundus of the gallbladder. The internal echo of the tumor was nonhomogeneous, and
      the structure of the gallbladder wall was partly torn. The common bile duct and
      the left intrahepatic bile duct were dilated. Abdominal computed tomography (CT)
      showed an elevated lesion with the same degree of imaging effect as that of the
      liver on the peritoneal side of the fundus of the gallbladder. The structure of
      the gallbladder was preserved, and the gallbladder was well demarcated from the
      surrounding tissue. No hepatic or lymph node metastases were noted. Endoscopic
      retrograde cholangiopancreatography (ERCP) visualized the pancreaticobiliary
      maljunction where the pancreatic duct joined the bile duct, entering an
      approximately 2-cm-long common channel. Dilatation of the common bile duct and
      intrahepatic bile ducts was observed and diagnosed as the IV-A type according to
      the Toya classification. Abdominal angiography in the arterial phase showed
      dilatation of the cystic artery and hyperplasia of vessels but no apparent
      encasement. In the venous phase, a deep-staining tumor was observed. From the
      above findings, we made a diagnosis of gallbladder cancer complicating
      pancreaticobiliary maljunction, and performed an operation. Since intraoperative
      US showed that the outermost layer of the gallbladder was in part ill-demarcated,
      we diagnosed the depth of penetration as ss, and performed cholecystectomy and
      bile duct resection and hepatic resection (S4a and S5), and lymphnode dissection
      (D2; dissection of groups 1 and 2 lymphnodes). The resected specimen grossly
      showed a papillomatous lesion with a cauliflower-like surface. The
      histopathologic diagnosis was papillary adenocarcinoma, depth ss, stage II. Tumor
      cells proliferated in a papillomatous pattern and were mostly confined to the
      muscular coat but partly infiltrated into the subserosal coat. In the diagnosis
      of pancreaticobiliary maljunction, it is crucial to consider complicating
      gallbladder cancer.

PMID- 12235876
TI  - Minute lung carcinoma associated with focal honeycombed lesion.
AB  - We report a case of minute lung carcinoma that developed in a focal honeycombed
      lesion in the right lung. A 70-year-old man presented hemosputum, and a
      cytological examination result was at class IV. A right lower lobectomy of the
      lung was performed. Microscopically, the thickened alveolar wall revealed tumor
      cells indicating a minute carcinoma, and showed squamous hyperplasia, metaplasia,
      and dysplasia, with the carcinoma in the distal airway epithelium. This
      peripheral lung carcinoma in a focal honeycombed lesion demonstrated the various
      stages of multistep carcinogenesis, which is recognized in hilar type squamous
      cell carcinoma. To date, the association between a honeycombed lesion and lung
      cancer has been poorly described. Here we have presented clear evidence of the
      association of this carcinoma with the honeycombed lesion.

PMID- 12235877
TI  - Effect of AGEs on human disc herniation: intervertebral disc hernia is also
      effected by AGEs.
AB  - Currently, extracellular matrix MMP has been discussed in relation to the
      extrusion and spontaneous regression of the herniated mass observed in lumbar
      disc herniation. However, the question remains as to whether degenerated protein
      is really the cause of this condition's pathogenesis. We confirmed
      immunologically by means of electron microscopy that extrusion is caused by the
      AGEs (advanced glycation end products)-induced cross-linking of collagen, and
      that spontaneous regression is due to AGE receptors on macrophages. Further, AGEs
      were found to be already exposed during histogenesis, suggesting a relation to
      apoptosis. In lumbar disc herniation and aging, glucose-derived AGEs cross-link
      proteins and cause vascular tissue damage.

PMID- 12235878
TI  - A case report of disseminated recurrence of inferior bile duct carcinoma in PTCD
      fistula.
AB  - We report a case of disseminated recurrence of inferior bile duct carcinoma
      growing in the fistula where the percutaneous transhepatic cholangiodrainage
      (PTCD) catheter was instituted. The recurrent tumor seemed to be implanted by
      dissemination of the original tumor during the first surgery. We could
      successfully remove this recurring tumor with lateral segmentectomy of the liver
      plus peritoneal dissection. This patient had been followed after the first
      surgery (pancreaticoduodenectomy) for inferior bile duct carcinoma causing
      obstructive jaundice. CEA and CA19-9 raised and CT scan confirmed the recurrent
      tumor in the lateral segment of the liver. This patient has been in good
      condition for 2 years following the second surgery.

PMID- 12235879
TI  - A case report of off-pump coronary artery bypass grafting associated with recent
      neurological deficit.
AB  - A 77-year-old man with a history of cerebral infarction was admitted to our
      hospital with chest oppression. Coronary angiography revealed 2-vessel disease
      involving left main trunk. Coronary artery bypass grafting to left anterior
      descending artery and obtuse marginal branch was scheduled, but the patient
      developed hemiparesis and the scheduled coronary artery bypass grafting was
      postponed by at least one month. Unfortunately, the patient complained of severe
      chest pain at midnight of the second day from the onset of the neurological
      deficits and went into cardiogenic shock. We performed off-pump coronary artery
      bypass grafting to left anterior descending artery on the 5th day from the onset
      of the neurological deficits. His postoperative course was uneventful. Off-pump
      coronary artery bypass grafting is appropriate as an alternative procedure for
      high-risk patients with recent neurological deficits.

PMID- 12235880
TI  - [Otitis media with effusion: a study of 346 cases in an outpatient clinic].
AB  - We treated 346 patients with otitis media with effusion (OME) and 30 (127
      episodes) with recurrent acute suppurative otitis media at our outpatient clinic
      in the 6 years from October 1994 to September 2000. Of these, children under 15
      years old numbered 185, mostly boys at a ratio of 1.4: 1.0, while patients aged
      15 years or older numbered 161, mostly females at a ratio of 1.3: 1.0. In
      children, 24 were excluded due to a lack of diagnostic follow-up, 65 (40%)
      patients improved in conservative management of medication with and without
      repeated tubal inflation, 79 (49%) improved by paracentesis, and 18 (11%)
      recovered with the use of pressure equalization tubes (grommets). Of cases aged
      15 years or older, follow-up was not possible in 28. Three (2%) were free of OME
      by conservative treatment, 116 (87%) improved by paracentesis, and 9 (7%) by
      using tubes. The mean durations of tube insertion was 11.3 months in children and
      7.2 months in adults, but 5 adults (4%) continue being treated of this writing.
      Bilateral cases were 30% of children and 8% of adults with 73% of children
      affected bilaterally having persistence or recurrence. Acute purulent otitis
      media progressed to OME in 22% of children but only in 3% of patients aged 15 or
      older. In 36% of children and 26% of patients aged 15 or older, acute upper
      respiratory tract infection coincided with or predisposed to OME. Rhinosinusitis
      was seen in 19% of children and 14% of adults. Coincident allergic rhinitis was
      seen in 14% of children and 12% of adults with OME. Nasopharyngeal infection and
      allergy are likely related to OME development. The peak incidence of OME was
      similar to that of recurrent suppurative otitis media in children, so a seminal
      precipitating factor appears to result in these 2 conditions.

PMID- 12235881
TI  - [Expression and localization of the inducible isoform of nitric oxide synthase in
      nasal polyps].
AB  - Nitric oxide (NO) and peroxynitrite play an important role in pathophysiology of
      several airway diseases. An inducible isoform of nitric oxide synthase (iNOS) is
      known to be expressed in the nasal mucosa in allergic and chronic rhinitis. Few
      reports exist, however, on the expression of iNOS in nasal polyps. We detected
      and localized iNOS expression in nasal polyp tissue. Nasal polyps were obtained
      from 10 patients following polypectomy, and divided into allergic and infectious
      groups based on clinical presentation and laboratory testing. One nasal mucosa of
      the inferior turbinate was also obtained from a cadaver without nasal disease.
      iNOS expression was studied by immunohistochemistry under light and electron
      microscopy. Immunoreactivity for iNOS was localized to the mucosal epithelium,
      inflammatory cells, vascular endothelium and smooth muscle, and nasal gland.
      Strong immunoreactivity was shown in the mucosal epithelium of both groups, and
      weak to moderate reactivity in the mucosal epithelium of the inferior turbinate.
      Vascular endothelium and smooth muscle of both groups sometimes showed weak to
      moderate immunoreactivity. Nasal glands of both groups sometimes showed weak
      immunoreactivity. A significant difference between allergic and infectious groups
      was observed in predominant types of inflammatory cells. Neutrophils were
      predominant in the infectious group (p < 0.01), and eosinophils in the allergic
      group (p < 0.0001). About 50%-53% in allergic and 42% in infectious groups--of
      inflammatory cells showed positive immunoreactivity for iNOS. Immunoreactive
      cells were neutrophils, eosinophils, and macrophages. Lymphocytes, plasma cells,
      and mast cells invariably reacted negatively. A significant difference between
      allergic and infectious groups was observed in predominant iNOS-immunoreactive
      cells. Ratios of immunoreactive neutrophils to all neutrophils (p < 0.05) and to
      all inflammatory cells (p < 0.05) were significantly higher in the infectious
      group. The ratio of immunoreactive eosinophils to all inflammatory cells was
      significantly higher in the allergic group (p < 0.0001), while the ratio of
      immunoreactive eosinophils to all eosinophils did not differ between infectious
      and allergic groups. The ratios of immunoreactive macrophages to all macrophages
      and to all inflammatory cells did not differ significantly between groups.
      Electron microscopy showed that degenerated cells with pyknotic nuclei were
      located next to immunoreactive eosinophils, suggesting the cytotoxicity of NO,
      peroxynitrite, or superoxide.

PMID- 12235882
TI  - [Squamous carcinoma of the posterior oropharyngeal wall].
AB  - We treated 9 patients with squamous cell carcinoma of the posterior oropharyngeal
      wall at the Cancer Institute Hospital, Tokyo. All were men averaging 64.1 years
      of age. One patient each was stage I, stage II or stage III, and 6 were stage IV.
      Cervical lymph node metastasis was seen in 6 at initial diagnosis.
      Retropharyngeal lymph nodes were involved in 4, while 5 had second primary cancer
      such as esophageal, gastric, head and neck cancer. Radical radiotherapy was done
      for 3 and surgery as initial treatment in 6. Five-year local control was 50% and
      5-year disease-free survival was 22%. Total laryngectomy was done for 4 patients.
      Six died of oropharyngeal cancer and 1 of second primary cancer. Cancer of
      posterior pharyngeal wall is relatively rare and the prognosis is considered
      poorer than other types of oropharyngeal cancer for necessitating study to
      determine which modality may improve treatment results.

PMID- 12235883
TI  - [Evaluation of deformation after auricular cartilage collection].
AB  - We studied the occurrence of deformation after collection of auricular cartilage.
      Subjects numbered 28 (15 with auricular cartilage collection and 12 without
      serving as a control group). We measured ear length, ear width, ear attachment
      length, auricular cartilage length, auricular lobe length, and auricle height,
      evaluating questionnaires given to subjects. Results showed that the collection
      of auricular cartilage does not result in deformation. In conclusion, the
      collection of auricular cartilage has few risks in view of cosmetics.

PMID- 12235884
TI  - [A rare case of the high jugular bulb associated with only hearing ear].
AB  - The jugular bulb may be present in different positions and dimensions within the
      temporal bone. In general, high jugular bulbs were classified into 2 types:
      lateral in which the jugular bulb protrudes into the middle ear and up into the
      tympanic cavity and medial in which the jugular bulb is abnormally placed more
      superiorly and medial to the cochlea. We report, a unique case of a high jugular
      bulb which came round from behind of the internal auditory canal and the cochlea
      protruding into the posterosuperior part of the mesotympanum. It was a very rare
      pattern of a high jugular bulb which varies in position. The occurrence of
      adhesive otitis media caused the high jugular bulb to bleed easily in the only
      hearing ear. There would be risks of making the patient suffer severe bilateral
      healing impairment due to only one hearing ear and excessive hemorrhage in
      surgical treatment. With only one hearing ear, we should therefore select
      transcatheter interventional angiography when the quantity and frequency of
      bleeding from the jugular bulb increase so.

PMID- 12235885
TI  - [Postpartum hypercalcemia in a patient with previous thyroid carcinoma: a report
      of 2 cases].
AB  - We report postpartum hypercalcemia in 2 patients with previous thyroid carcinoma
      who had undergone total thyroidectomy and total parathyroidectomy and required
      vitamin D and calcium therapy to control hypoparathyroidism. Postpartum, they
      required less vitamin D and calcium for satisfactory control. While lactating,
      they maintained normal serum calcium without supplementary vitamin D or calcium.
      Transient remission of hypoparathyroidism symptoms has been observed during
      lactation. Some studies have shown that parathyroid-related protein (PTHrP) is
      produced by breast tissue, having an endocrine-like effect. We discuss the
      mechanism of postpartum hypercalcemia.

PMID- 12235886
TI  - Appeals Court affirms trial court's refusal to grant preliminary injunction to
      enforce restrictive covenant. Premier Health Care Services v. Schneiderman.

PMID- 12235887
TI  - Dismissal of informed consent claim upheld by California Appellate Court. Schiff
      v. Prados.

PMID- 12235888
TI  - Hospital trusts. Tandem factor.

PMID- 12235889
TI  - US healthcare. Unequal opportunities.

PMID- 12235890
TI  - Primary care. Social skills.
AB  - A scheme attaching social workers to general practices to improve services for
      older people is thought to have cut delays and increased communication between
      social services and primary care. The engagement of practice managers is key to
      the success of the venture. Seeing a social worker in general practice is thought
      to lessen the stigma some older people feel about referral to social services.

PMID- 12235891
TI  - Delivery units. From here to maternity.
AB  - A review of activity in a delivery suite in an acute hospital found that many
      women were there for reasons unconnected to labour, or because a bed could not be
      found in the hospital's maternity wards. Midwives have established a two-bed
      assessment room next to the suite and set up a 24-hour telephone helpline. Women
      are encouraged to telephone for advice rather than turn up at the unit when they
      have problems with their pregnancy. These innovations, which have been in
      operation for a year, are believed to have reduced pressure on the delivery unit.

PMID- 12235892
TI  - Patient experience. Redesign for life.
AB  - The success of the government's modernization agenda in the NHS will depend on
      services being considered from the point of view of the patient journeying
      through the system. Restructuring organizations does not, on its own, improve
      care. Services cannot be improved without the involvement of staff, who may well
      be demoralized by the frequent organisational upheavals.

PMID- 12235893
TI  - Hospital catering. Hard to swallow.
AB  - Hospital meals cost the NHS, on average, 2.50 Pounds per patient per day. Costs
      are higher in hospitals which prepare food on site, specialist trusts and those
      in London. The Wanless report has proposed that expenditure should rise to 4.80
      Pounds per patient per day, at today's prices, by 2022. More effort should go
      into cutting food wastage which currently costs hospitals in England more than 18
      m Pounds a year.

PMID- 12235894
TI  - [The Revista Medica the Chile and medical education].
AB  - With this issue, Revista Medica de Chile will have been published
      uninterruptedly, for 130 years. Formal medical education had an early development
      since Chile became independent from Spain (1817). The first Medical Sciences
      Course was organized in 1833 by the Irish physician William C Blest. The Santiago
      Medical Society was founded in 1869 and its journal-Revista Medica de Chile--in
      1872. Its first director was Dr. German Schneider. Revista Medica is the oldest
      serial publication in South America and the second oldest in the Spanish speaking
      world. This is a remarkable fact for a comparatively young country. With the
      creation of the Medical Society and Revista Medica, a process of continuous
      medical education was started and they became a real Graduate School. The Journal
      has adopted the main changes in knowledge and technology. Some important
      milestones of its development, during the second half of the 20th century, were
      the definition of its objectives and structure, the incorporation of peer review
      of manuscripts (even with foreign reviewers) the adoption of international
      guidelines for publication, its incorporation into the main biomedical journal
      indexes, the modernization of its printing process, the making of a computer
      generated index of all papers published since 1872, its incorporation into a
      digital library in INTERNET and the active participation of its editors in the
      World Association of Medical Journal Editors. The success of the journal is
      influenced by the independence that the Medical Society has conferred to the
      editors (all outstanding University Professors), as well as to the
      characteristics of an educational campus "invisible and without tumult"
      (Ingelfinger).

PMID- 12235895
TI  - [Natural history of cholelithiasis and incidence of cholecystectomy in an urban
      and a Mapuche rural area].
AB  - BACKGROUND: Cholelithiasis is the second cause of hospital admissions in Chile.
      AIM: To study the prevalence of symptomatic gallstone disease and opportunity of
      cholecystectomy in La Florida, Santiago and among Mapuche Indians in Huapi
      Island. PATIENTS AND METHODS: In the period 2000-2001, we contacted to 71% (1127
      subjects) and to 61% (145 subjects) patients of La Florida and Huapi Island,
      respectively, that had previously participated in an epidemiological study on
      cholelithiasis in 1993. We defined symptomatic gallstone patients as those with a
      history of biliary colic. Each patient was subjected to gallbladder ultrasound.
      RESULTS: In 1993, 30-35% of gallstone patients were symptomatic (approximately
      70% women). During the lapse 1993-2001, only 50% of subjects from La Florida and
      25% of patients from Huapi Island were cholecystectomized (p < 0.05). Fifty
      percent of cholecystectomies were emergency operations. In 38 symptomatic Mapuche
      Indians from Huapi, cholecystectomy was indicated in 2001. After five months of
      the indication, only one of these subjects had been operated. Laparoscopic
      cholecystectomy represented 40% of all cholecystectomies performed in the
      National Health Service Hospitals. CONCLUSIONS: This study demonstrates an
      unacceptable high prevalence of symptomatic gallstone patients remaining non
      operated in both the urban and rural communities. This reciprocally correlates
      with the high frequency of emergency cholecystectomies and the high incidence of
      gallbladder cancer among Chileans. This study contrasts negatively with the
      situation of Scotland, where 73.5% of cholecystectomies were laparoscopic in 1998
      1999. To reach Scotland standards, the Chilean Public Health System should
      increase the number of cholecystectomies from 27,000 in 2001 to 57,510

PMID- 12235897
TI  - [Pilot study of PML/RAR alpha fusion by fluorescence in situ hybridization
      (FISH)method in acute promyelocyte leukemia].
AB  - BACKGROUND: Acute promyelocytic leukemia (APL) is characterized cytogenetically
      by t(15;17) (q22;q21) and its molecular consequence, fusion of PML and RAR alpha
      genes. The detection of this genetic marker confirms the diagnosis and allows
      monitoring of the leukemic clone during treatment, which has prognostic value.
      Cytogenetics fails in some cases due to the absence of metaphases in cultures or
      their bad morphology. Southern blot and PCR methods require trained personnel and
      adequate equipment. FISH method allows the identification of chromosomic
      rearrangements in 24 to 48 h and is simple to set up in a cytogenetics
      laboratory. AIM: To evaluate the FISH method to detect PML/RAR alpha fusion,
      compared to cytogenetic analysis. PATIENTS AND METHODS: Fifteen bone marrow
      specimens from APL patients with previous cytogenetic analysis were studied,
      using a commercial probe to detect PML/RAR alpha fusion. RESULTS: We obtained a
      normal cut-off value of 9.1%. Specificity and sensibility were 100%. Six positive
      cytogenetic cases at diagnosis were FISH positive. Six negative cytogenetic
      cases, one APL at diagnosis and five normal controls were FISH negative. One case
      in remission, that was negative by cytogenetics, was positive near the cut-off
      value by FISH. Two other cases in remission, not conclusive by cytogenetics, were
      negative by FISH. CONCLUSIONS: FISH is a reliable, rapid and relatively low cost
      method that can be used as an adjunct to conventional cytogenetics.

PMID- 12235896
TI  - [Obesity: risk factor for steatohepatitis and hepatic fibrosis].
AB  - BACKGROUND: Nonalcoholic fatty liver (NAFL) has been recognized as a cause of
      chronic liver disease. Its main risk factor is obesity. AIM: To describe the
      clinical and liver pathological findings in a group of patients who underwent
      surgery as obesity treatment. PATIENTS AND METHODS: Sixty eight patients with
      severe or morbid obesity were subjected to surgery as obesity treatment. Each
      patient was evaluated with a complete clinical and laboratory medical assessment.
      A wedge of liver was excised during surgery. Liver biopsies were analyzed without
      knowledge of clinical and laboratory findings. The presence of steatosis,
      inflammation (portal or lobular), fibrosis and cirrhosis were recorded in the
      pathological analysis. Age and body mass index (BMI) were correlated with
      pathological data. Significance was set at a p value of less than 0.05. RESULTS:
      Ninety one percent of patients had steatosis, 45% inflammation and 47% fibrosis.
      One patient had cirrhosis (1.4%). There was a statistically significant
      association between BMI and moderate or severe steatosis (p < 0.03). There was
      also an association between BMI and portal (p = 0.017) and lobular inflammation
      (p = 0.034). A BMI over 40 kg/m2 (morbid obesity) was significantly associated
      with the presence of fibrosis (p = 0.032). Moreover, the presence of moderate or
      severe steatosis was a risk factor for the development of hepatic fibrosis (p =
      0.026). CONCLUSIONS: Obesity is a major and independent risk factor for
      steatohepatitis and fibrosis. The degree of steatosis in the liver biopsy, is a
      risk factor for the development of fibrosis.

PMID- 12235898
TI  - [Favorable reproductive and menstrual evolution in adult women, who presented in
      the adolescence, menstrual disturbances by hypothalamic dysfunction and lack of
      response to clomiphene].
AB  - BACKGROUND: Hypothalamic dysfunction is a cause of menstrual disturbances in
      women, in whom other diseases have been discarded. This condition is
      characterized by a failure of the GNRH pulse generation system and is associated
      to psychological and environmental factors. A lack of ovulatory response to the
      administration of clomiphene can be a sign of bad prognosis in hypothalamic
      dysfunction. AIM: To report the natural history of patients with hypothalamic
      dysfunction and a bad or deficient response to the administration of clomiphene.
      PATIENTS AND METHODS: Fifty patients with hypothalamic dysfunction, that
      consulted for menstrual disturbances at the age of 15 to 20 years old, were
      studied. All received clomiphene and 31 had an ovulatory response, 12 had menses
      without ovulation and 7 did not menstruate. Of these 19 women eleven were
      interviewed again about their menstrual and reproductive history, after a lapse
      of 9 to 17 years of loss from follow up. RESULTS: Eight of the eleven women had
      stressful events during adolescence (going away from family house in 3, starting
      university studies in 3, migration out of the natal country in one and non
      competitive physical activity in one). All restarted their menses and eight with
      active sexual life had spontaneous pregnancies, giving birth from two to five
      children. Ovulatory cycles were documented in women without active sexual life.
      CONCLUSIONS: In teenagers with hypothalamic dysfunction and menstrual
      disturbances, a deficient or bad response to clomiphene does not necessarily
      indicate a bad prognosis in terms of menses or fertility.

PMID- 12235899
TI  - [Analysis of referrals of new patients to the rheumatology section of a tertiary
      hospital].
AB  - BACKGROUND: The prevalence of rheumatic diseases is approximately 15% in the
      general population. AIM: To assess the concordance between the original and final
      diagnosis of patients referred to a rheumatology unit. PATIENTS AND METHODS:
      During 2000, all new patients referred to the rheumatology section of Temuco
      General Hospital were recorded. The concordance between the referral diagnosis
      given by general practitioners or general internists and the final diagnosis
      reached at the rheumatology unit was analyzed using the Kappa index. The modified
      version of the American College of Rheumatology nomenclature was used as
      reference. RESULTS: The clinical records of 787 outpatients, 83% females, aged
      54.7 +/- 14 years old, were analyzed. Twenty seven percent of patients were
      referred with the diagnosis of connective tissue diseases, 26% with extra
      articular diseases and 24% with osteoarthritis. The concordance between referral
      and final diagnosis reached at the rheumatology unit had a kappa of 0.6 for
      general practitioners and 0.72 for general internists. CONCLUSIONS: Although the
      overall concordance between referral diagnosis, given by general practitioners or
      general internists, and final rheumatological diagnosis is good, there are still
      major discrepancies that should be improved.

PMID- 12235900
TI  - [Acoustic analysis of wheezing in infants with acute bronchial obstruction. A
      follow-up study ].
AB  - BACKGROUND: There is some information about wheeze characteristics in infants,
      however it is not clear whether the different wheeze patterns relates to
      prognosis and evolution during the first two years of life. OBJECTIVES: To
      characterize wheezing and spectral pattern of lung sounds in infants with acute
      bronchiolitis (AB) and in infants with recurrent wheeze (RW) as well as to
      compare these parameters with the clinical evolution 2 years after admission.
      METHODS: Seventy six AB infants (48 boys), aged 5.5 +/- 0.7 months (mean +/- SD),
      62 RSV (+) and 32 RW infants (20 boys), aged 11.4 +/- 2 months were studied
      during the first week of admission at the hospital. Patients were studied during
      spontaneous sleep, breathing with a face mask connected to a pneumotachograph at
      flows of 0.1 +/- 0.02 L/s. Sounds were registered at baseline and 20 minutes
      after salbutamol using 2 contact sensors placed at both lower lobes levels.
      Signals were low-pass filtered, amplified and a Fourier analysis was applied to
      sounds within a target flow range. Spectral analysis was done between 100 and
      1000 HZ. RESULTS: In 40/76 (53%) AB vs 30/34 (88%) RW sinusoidal wheezing (p <
      0.01; chi 2) were observed and a positive bronchodilator response was obtained in
      37/76 (49%) AB vs 32/34 (94%) RW (p < 0.01; chi 2). Patients with sinusoidal
      wheezing (s-w) had more wheezing episodes in follow-up, 26/40 vs 8/36 in complex
      wheezing (c-w), (p < 0.01: chi 2) and 30/34 in RW (p < 0.01; chi 2). IgE values
      at 18 months were higher in s-w compared to c-w (63 +/- 7 vs 24 +/- 5 Iu/mL (p <
      0.01) and 96 +/- 11 Iu/mL in RW (p < 0.01). CONCLUSIONS: a) Wheezing
      characteristics in acute bronchiolitis vs recurrent wheezing are different; b)
      Bronchodilator response relates to wheeze characteristics and c) Higher IgE and
      more recurrent wheezing episodes are seen in acute bronchiolitis with sinusoidal
      wheezing. These findings suggest that lung sounds analysis is useful in assessing
      wheezy patients and have a value to identify infants on risk of developing
      asthma.

PMID- 12235901
TI  - [Continuous hemofiltration in patients with abdominal complications of hemolytic
      uremic syndrome].
AB  - BACKGROUND: Close to one half of patients with hemolytic uremic syndrome (HUS)
      will require a dialytic therapy, mainly peritoneal dialysis (PD). In some cases,
      PD may have relative or absolute contraindications, usually when HUS is
      associated to severe intraabdominal complications. AIM: To report the results of
      continuous hemofiltration use, in children with abdominal complications of HUS.
      MATERIAL AND METHODS: Retrospective review of the files of 40 patients that were
      admitted to our pediatric unit with HUS, since 1995. Six children had relevant
      intra-abdominal complications and were treated with continuous hemofiltration
      (CHF). Four additional children, with similar HUS related complications and
      treated with CHF before 1995, were included in the analysis. RESULTS: The age of
      the patients ranged from 5 to 66 months old. An arterio-venous CHF was performed
      in four and veno-venous CHF in six children. The duration of CHF was 93.2 hours
      in average. Adequate control of volemia was achieved in every patient;
      diafiltration with peritoneal dialysis solution was added in five patients, to
      improve azotemia. Four patients had complications related to the vascular access
      or the anticoagulation procedure. The procedure was terminated due to improvement
      of diuresis in five cases, transfer to PD in four and a cardiorespiratory arrest
      in one. Only one patient developed a chronic renal failure during the follow up.
      CONCLUSIONS: CHF is an effective and safe alternative of acute renal replacement
      therapy in the management of renal failure in pediatric cases with HUS,
      aggravated with abdominal complications.

PMID- 12235902
TI  - [Authorship in the Chilean journal Revista de Otorrinolaringologia y Cirurgia de
      Babeza y Cuello: analysis of three decades].
AB  - BACKGROUND: The number of authors of scientific papers has increased
      significantly in the last decade. The increasing complexity of medical research
      but also vicious practices are possible causes of this trend. AIM: To analyze the
      number of authors and type of papers published in the Chilean Journal of
      Otorhinolaryngology and Head and Neck Surgery in the last three decades. MATERIAL
      AND METHODS: A review of all manuscripts published between 1970 and 1999. The
      number of authors and the type of paper was registered. RESULTS: Five hundred
      nineteen papers were reviewed. The mean number of authors per paper increased
      from 1.9 to 3 (p < 0.001). Research reports decreased from 79% to 61% and the
      number of review articles and case reports increased. No multicentric work was
      published in the period. CONCLUSIONS: A significant increase in the number of
      authors per manuscript was observed in this review.

PMID- 12235903
TI  - [Liver transplantation in adults: a caseload from Clinica Alemana de Santiago,
      Chile].
AB  - BACKGROUND: The success of orthotopic liver transplantation (OLT) has resulted in
      its widespread use for different liver diseases. AIM: To report our 8 years
      experience with adult OLT at Clinica Alemana de Santiago. PATIENTS AND METHODS:
      In all transplantations done at the center, we recorded patient's overall data
      and survival, postoperative medical and surgical complications and causes of
      death. RESULTS: Between November 1993 and September 2001, 51 consecutive OLT were
      performed in 44 patients (22 females, median age 45 years old). Thirty eight
      patients presented with chronic and 6 with acute or sub-acute liver failure.
      Cryptogenic cirrhosis and hepatitis C infection were the most common causes for
      OLT. Postoperative bleeding and extrahepatic biliary complications were seen in
      17.6 and 21.5% of cases respectively. Acute rejection, bacterial infections, CMV
      infection or disease and post OLT hemodialysis were the most common medical
      complications (51, 31, 19.6 and 19.6% of cases respectively). The overall 1 and 5
      years survival rates were 80% and 73% respectively. Considering exclusively the
      last 22 OLT performed since January 1999, the 1 year survival rate has improved
      to 91%. CONCLUSIONS: Liver transplantation in Chile provides a good long term
      survival with acceptable morbidity, due to a multidisciplinary approach
      management. The survival rates have improved over the last few years probably due
      to better surgical techniques, ICU care and immunosuppression. These overall
      results are comparable with those from other Centers in developed countries.

PMID- 12235904
TI  - [Vibrio vulnificus: an infrequent cause of septic shock].
AB  - Vibrio vulnificus is a lactose positive Gram negative rod that lives in warm seas
      and can infect wounds and produce sepsis. Its infection is acquired after eating
      oysters or other filtering marine organisms. We report a 53 years old diabetic
      male who started with fever after a voyage to Central America. He was admitted
      febrile, hypotense, dehydrated and polypneic. Painful erythematous lesions and
      lumps were observed in his upper and lower limbs. After 72 hours of evolution,
      the lesions became violaceous, with crepitating vesicles full of hemorrhagic
      exudate. He developed a renal failure and a disseminated intravascular
      coagulation. Blood cultures demonstrated the presence of Vibrio vulnificus and
      the patient died 68 hours after admission.

PMID- 12235905
TI  - [Siliconomas. A case report].
AB  - In the early 1950s, the liquid silicone breast injection technique was developed
      in Japan. This breast augmentation method had local and systemic complications.
      Nevertheless, this technique is still used in some countries like Chile. We
      report a 41 years old woman, consulting due to breast pain and a nodule in her
      left breast. The clinical work up confirmed the presence of siliconomas, caused
      by silicone breast injections one year before. The physical and radiological
      findings (mammograms, ultrasound and breast MRI) of this woman are reported.

PMID- 12235906
TI  - [Bone marrow aplasia associated to the use of ticlopidine].
AB  - We report a 58 years old male that developed a bone marrow aplasia associated to
      the use of ticlopidine, prescribed after coronary artery stenting. The patient
      developed a pneumonia as a complication. He was admitted to the Intermediate
      Treatment Unit, receiving wide spectrum antimicrobial therapy and a granulocyte
      colony stimulating factor (Neupogen(r)) with favourable response. Ticlodipine is
      an effective antiplatelet agent, but has serious hematological and other side
      effects. Its prescription requires a close follow up and search for
      complications.

PMID- 12235907
TI  - [Severe chronic constipation. Is it a problem of surgery?].
AB  - Severe chronic constipation is defined as less than two bowel movements per week,
      hard stools, non productive urgency and the need of digital maneuvers in more
      than 25% of bowel evacuations. The best studied causes of chronic severe
      constipation are slow bowel transit constipation and pelvic floor dysfunction.
      However, there are mixed forms that cross link with irritable colon syndrome. The
      main diagnostic tests are anorrectal manometry, bowel evacuation, X-ray studies
      and anorrectal sphincteromyomectomy, that can be therapeutic. Five percent of
      patients are surgical candidates. In cases of slow bowel movement, total
      colectomy with ileorectal anastomosis has satisfactory results in 80 to 90% of
      patients. Some patients with pelvic floor dysfunction have an occult rectal
      prolapse, rectocele or sigmoidocele and obtain benefits with the correction of
      these conditions. The remaining patients require a training of bowel evacuation,
      known as biofeedback. We have performed a total colectomy in 10 patients with
      slow bowel movements with good functional results in 80%. After 56 months of
      follow-up, a mean 2.6 bowel movements per day is reported by the patients. Four
      patients were also operated due to a solitary rectal ulcer and two patients due
      to a sigmoidocele, with satisfactory results.

PMID- 12235908
TI  - [Un analysis of present situation of medical specialties un Chile].
AB  - During the fifties and sixties, physicians were mostly prepared as general
      practitioners. However, the progress in scientific knowledge and the introduction
      of complex technologies required the training of specialists. A number of sub
      specialties have been progressively added to the four basic specialties, namely
      Internal Medicine, Pediatrics, Obstetrics and Gynecology and General Surgery. The
      Post Graduate Schools of the traditional universities devised courses and
      training periods to teach these sub specialties. The Association of Medicine
      Schools has been in charge of the accreditation of the new training centers.
      Since the training of new specialists required the collaboration of hospitals of
      the public National Health Service, there is a special commission that
      coordinates the relationships between teaching requirements and medical attention
      in these hospitals. There is still a controversy on the exact proportion of
      general practitioners and specialists that the country needs, the role of Family
      Practice and the role of prevention and health promotion.

PMID- 12235909
TI  - [Application of Objective Structured Clinical Examination (OSCE) for pediatric
      internship assessment in two schools of medicine].
AB  - BACKGROUND: The Objective Structured Clinical Examination (OSCE) has become a
      respected and widely used tool for the assessment of clinical competence in
      medical education. AIM: To describe the first experience of an OSCE as a
      summative assessment in undergraduate Pediatric Internship, in two universities.
      MATERIAL AND METHODS: The OSCE was structured by a committee of faculty members
      of the 5 campi of University of Chile and I campus of the Catholic University. A
      21 station OSCE was administered simultaneously to 124 Pediatric Interns
      (University of Chile = 104, Catholic University = 20), in 3 centers. A total of
      50 faculty members participated in the examination. The OSCE consisted of 20
      clinical problems, including videotape recordings, photographs, x-rays and
      laboratory exams, phantoms and 7 simulated standardized parents. RESULTS: The
      average total OSCE score was 67.3% (range: 84.5%-43.5%). The maximum theoretic
      score was achieved in 19 stations. A significant correlation between station and
      total score, was found for 18 of the 20 clinical problems. CONCLUSIONS: The
      experience of using OSCE has been a success. The OSCE was an adequate procedure
      to assess a large number of interns simultaneously and it allowed us to measure
      the main objectives in all domains and a wide range of clinical competence of
      Pediatric Internship Programs.

PMID- 12235910
TI  - [The patient's autonomy].

PMID- 12235911
TI  - [Medical errors, why?].

PMID- 12235912
TI  - Reducing medical workload.

PMID- 12235913
TI  - Evaluation of immediate discharge documents--room for improvement?
AB  - BACKGROUND: The Immediate Discharge Document is a tool used to communicate
      patient discharge information between hospitals and general practitioners. The
      standard of information provided may be variable, and sometimes delayed in
      arriving at the GP practice. Typed communication from the hospital can also be
      slow. This can result in difficulty managing patients in the community following
      their discharge. Our aim was to assess the quantity of information provided on
      Immediate Discharge Documents, and to assess the time scale taken for GPs to
      receive written communications from hospitals regarding patient discharges. An
      audit was initiated using a tool devised from Scottish Intercollegiate Guidelines
      Network Publication no 5 and involving four general practices within City of
      Perth, Scotland. Data was collected over a 28-day period in June/July 2001, by
      examining Immediate Discharge Documents relevant to each practice population
      received during this period, and by noting the time of arrival of a final typed
      summary. Data was analysed by Tayside Audit Resource for Primary Care. A total of
      244 Documents were audited. Most significant results include basic administrative
      detail lacking in up to 30%. Of total documents, 13% failed to record a main
      condition or diagnosis; 93% recorded drug information, but only in 28% were
      follow up plans clear; 60% were received within five days of discharge, whilst
      final typed summaries were received from the hospitals within four weeks only in
      51%. CONCLUSION: These results show there to be room for improvement with regard
      communication of patient discharge information, in regard to both the content of
      information provided and the time it takes to arrive. We require to raise
      awareness of this problem amongst hospital colleagues involving clinical
      governance and audit staff, with the objective to improve the quality and
      timescale of information transfer. WHERE THIS PIECE FITS: It is known that
      effective information transfer between health professionals is vital to optimise
      patient care. This work gives further impetus to improve the current standard of
      communication, and confirms a significant time delay that it takes information to
      reach GPs from the hospital setting.

PMID- 12235914
TI  - Job satisfaction, work-related stress and intentions to quit of Scottish GPS.
AB  - Job satisfaction and work-related stress influence physician retention, turnover,
      and patient satisfaction. This study purports to elicit the views of Scottish GPs
      on job satisfaction, stress, intentions to quit, and to examine any patterns by
      demographic, job, and practice characteristics. A descriptive, cross-sectional
      study was undertaken by postal questionnaire on a random sample of 1,000 GP
      principals, 359 GP non-principals, and 62 PMS GPs. The response rate was 56%. GPs
      were most satisfied with their colleagues, variety in the job, and amount of
      responsibility given. The most frequently mentioned sources of job stress were
      increasing workloads, paperwork, insufficient time to do justice to the job,
      increased and inappropriate demands from patients. White, female, young (under 40
      years) and old (55 years and over) GP non-principals and PMS GPs who work less
      than 50 hours per week as a GP were more likely to be satisfied with their job
      and reported lower levels of stress. CONCLUSIONS: GP participation in the
      workforce could be promoted by introducing more flexible working patterns (e.g.
      part-time work), by expanding the scope of contractual arrangements, and by
      making patient expectations more realistic by clearly communicating what the role
      of a GP actually encompasses.

PMID- 12235915
TI  - Human subcutaneous dirofilariasis: a report of three cases manifesting as breast
      or axillary nodules.
AB  - Human subcutaneous dirofilariasis is a rare infection caused by filarial worms of
      the genus Dirofilaria. The parasites are transmitted to man by zooanthropophilic
      bloodsucking insects and the infection is manifested as subcutaneous nodules.
      Excisional biopsy is both diagnostic and therapeutic. We herein report three
      cases of human subcutaneous dirofilariasis diagnosed, over a period of ten years
      (1991-2000), in North East Greece. The patients, two women and one man, were all
      adults between 32 and 67 years of age. In two cases the infection was manifested
      as breast nodules, while in the third case as a painful nodule in the axillary
      region. The excisional biopsy showed the presence of an adult Dirofilaria,
      identified as Dirofilaria (Nochtiella) repens. It is emphasised that both
      clinicians and pathologists should have an increased awareness of this
      clinicopathologic entity and include dirofilariasis in the differential diagnosis
      in patients presenting with breast or subcutaneous nodules.

PMID- 12235916
TI  - Archie Cochrane.

PMID- 12235917
TI  - Dishonesty, misconduct and fraud in clinical research: an international problem.
AB  - Clinical research misdemeanours include a broad spectrum of misdeeds that
      misappropriate an unfair advantage or harm the rights of others. There is no
      internationally accepted definition of such malpractices and no generalized
      procedure to facilitate their reporting or correction. Those who do report
      research misdemeanours are often stigmatized as 'whistleblowers', a term that has
      acquired many negative connotations. Frequently, whistleblowers encounter many
      personal conflicts and/or may suffer victimization in their working environment.
      There remains a need for an internationally harmonized approach to manage these
      unacceptable problems. Resolution of such important issues should be catalysed by
      the impending need for European Union states to implement Good Clinical Practice
      Directive 2001/20/EC into national law.

PMID- 12235918
TI  - A new fixed-dose combination for added blood pressure control: telmisartan plus
      hydrochlorothiazide.
AB  - Population surveys on hypertension management reveal worrying deficiencies in the
      awareness and treatment of high blood pressure. Many patients with hypertension
      will require two or more drugs with complementary mechanisms of action (which
      generally have additive effects, producing greater blood pressure reductions than
      either agent alone) to attain the blood pressure goals specified in
      internationally accepted guidelines. Nevertheless, physicians are often reluctant
      to prescribe multiple anti-hypertensive drugs due to concerns over side-effects,
      inconvenient dosing regimens and costs. Fixed-dose formulations combining two
      agents from different classes in a single tablet should help to allay these
      concerns. A fixed-dose combination containing telmisartan (an angiotensin II
      receptor blocker) and hydrochlorothiazide (a thiazide diuretic) has recently been
      developed. Telmisartan/hydrochlorothiazide provides additional anti-hypertensive
      efficacy compared with the respective monotherapies in a wide range of patients,
      including black patients, requires once-daily dosing, is cost-effective, well
      tolerated and is associated with less potassium depletion than
      hydrochlorothiazide administered alone.

PMID- 12235919
TI  - The role of triple therapy, age, gender and smoking on the genotoxic effects of
      Helicobacter pylori infection.
AB  - The role of age, gender and smoking on both the genotoxic effects of Helicobacter
      pylori and the efficacy of eradication therapy in a group of patients with
      gastritis was investigated. Gastritis was confirmed by endoscopy and biopsy, and
      the presence of H. pylori by urease testing. Pre- and post-treatment peripheral
      blood lymphocyte cultures were prepared from 17 patients and 25 metaphases per
      patients were analysed for sister chromatid exchange (SCE), a well-established
      technique for the evaluation of human exposure to toxic agents. Treatment with
      omeprazole, clarithromycin and amoxycillin triple therapy eradicated H. pylori in
      94% of patients and significantly reduced the SCE frequency. Pre-treatment SCE
      frequency was found to be positively correlated with age. Female smokers tended
      to have higher post-treatment SCE frequencies than male smokers, and pre- and
      post-treatment SCE frequencies were higher in older males than in older females.
      Eradication therapy decreased the genotoxicity of H. pylori, but age in males and
      smoking in females may decrease treatment efficacy.

PMID- 12235920
TI  - Serum interleukin 2 levels in patients with rheumatoid arthritis and correlation
      with insulin sensitivity.
AB  - Interleukin 2 (IL-2), a Th1 lymphocyte-derived cytokine, is thought to play an
      important role in the pathogenesis of type 2 diabetes and rheumatoid arthritis
      (RA). The aim of our study was to evaluate changes in serum IL-2 levels and their
      correlation with glucose metabolism abnormalities, such as insulin resistance, in
      patients with RA. Thirty-six subjects with varying degrees of disease activity
      and 20 healthy age-, sex- and body mass index-matched control individuals were
      evaluated. Patients with any causes of peripheral insulin resistance were
      excluded. After a 12-h overnight fast, fasting insulin levels, homeostatic model
      assessment-insulin resistance (HOMA-IR) estimated insulin sensitivity, and serum
      IL-2 levels were significantly higher in all patients with RA than in the control
      individuals. Fasting insulin, HOMA-IR scores and IL-2 levels were correlated in
      the RA group. This study showed that patients with RA have altered IL-2
      regulation, and that there was a significant correlation between serum IL-2
      levels and insulin sensitivity.

PMID- 12235922
TI  - Increased cytotoxicity of carbon tetrachloride in a human hepatoma cell line
      overexpressing cytochrome P450 2E1.
AB  - Cytotoxic free radicals generated during the metabolism of carbon tetrachloride
      by cytochrome P450 2E1 (CYP2E1) are thought to cause hepatotoxicity. Here, the
      cytotoxic effects of carbon tetrachloride in a liver cell line expressing CYP2E1
      (HLE/2E1) are compared with those in the mother cell line (HLE). The effects of
      carbon tetrachloride on the gene expression of HSP70, a potential marker of
      oxidative stress, were also examined. The viability of HLE/2E1 cells after
      exposure to carbon tetrachloride was significantly decreased compared with that
      of HLE cells. Northern blot analysis revealed that the HSP70 mRNA level was
      significantly increased after carbon tetrachloride treatment in both cell lines,
      while the magnitude of its increase was much greater in HLE/2E1 cells than in HLE
      cells. These results suggest that the oxidative stress induced by CYP2E1 plays an
      important role in the increase in cytotoxicity of carbon tetrachloride in CYP2E1
      overexpressing cells.

PMID- 12235921
TI  - Pharmacokinetics of rosiglitazone in patients with end-stage renal disease.
AB  - The pharmacokinetics and tolerability of a single 8-mg oral dose of
      rosiglitazone, an anti-diabetic agent, were compared in 10 long-term
      haemodialysis patients and 10 healthy volunteers. Haemodialysis patients received
      rosiglitazone 4 h after haemodialysis (non-dialysis day) and 3 h before
      haemodialysis (dialysis day). Haemodialysis did not influence rosiglitazone
      pharmacokinetics, and dialytic clearance was low (0.10 1/h). The mean area under
      the concentration-time curve (AUC(0-infinity)), the maximum observed plasma
      concentration (Cmax) and the half-life for rosiglitazone were similar in
      haemodialysis patients (non-dialysis day) and healthy individuals (2192 +/- 598
      ng.h/ml versus 2388 +/- 494 ng.h/ml, 338 +/- 114 ng/ml versus 373 +/- 95 ng/ml,
      and 3.70 +/- 0.75 h versus 3.81 +/- 0.86 h, respectively). AUC(0-infinity) and
      Cmax were not markedly influenced by haemodialysis. Rosiglitazone dose
      adjustments are not warranted in patients with type 2 diabetes with end-stage
      renal failure on haemodialysis.

PMID- 12235923
TI  - Comparative cochlear toxicities of streptomycin, gentamicin, amikacin and
      netilmicin in guinea-pigs.
AB  - All the aminoglycoside antibiotics now in clinical use are ototoxic. This study
      was designed to compare the toxic effects of four aminoglycoside antibiotics,
      streptomycin, gentamicin, amikacin and netilmicin, administered to guinea-pigs
      systemically (at respective doses of 125 mg/kg, 50 mg/kg, 150 mg/kg or 37.5
      mg/kg, twice daily for 1 week) or topically via the transtympanic route (0.25
      ml/kg in 4% saline, twice daily for 1 week). Chosen doses were 10-20 times higher
      than the recommended human dosage. Cochlear damage was observed in all animals
      that were given systemic and local aminoglycosides. The severity of the cochlear
      damage was in the order gentamicin, amikacin, streptomycin, netilmicin, with
      gentamicin being the most toxic. No statistically significant difference between
      the severity of cochlear damage resulting from the systemic and topical
      applications was detected.

PMID- 12235924
TI  - Polymorphism of CYP2C19 and gastric emptying in patients with proton pump
      inhibitor-resistant gastric ulcers.
AB  - The aim of the present study was to investigate whether CYP2C19 polymorphism
      status and gastric emptying are related to healing in patients with gastric
      ulcers. We studied the CYP2C19 status in seven patients with proton pump
      inhibitor (PPI)-resistant ulcers, 21 with PPI-sensitive ulcers and 46 healthy
      volunteers using polymerase chain reaction restriction fragment length
      polymorphism to detect CYP2C19m1 mutation in exon 5 and CYP2C19m2 mutation in
      exon 4. Gastric emptying was evaluated using the 13C-acetate breath test. The
      frequency of phenotypes, indicated by genotypes, did not differ significantly
      between the three patient groups. The peak time of 13C excretion in patients with
      PPI-resistant ulcers was significantly longer than that of patients with PPI
      sensitive ulcers and healthy volunteers. Our results suggest that rate of gastric
      emptying, but not CYP2C19 polymorphism, is likely to be an important factor in
      the delayed healing of patients with PPI-resistant gastric ulcer.

PMID- 12235925
TI  - Coryneform bacteria isolated from blood cultures and their antibiotic
      susceptibilities.
AB  - We aimed to determine the types of corynebacteria isolated from the blood of
      patients at Gaziantep University Hospital, Turkey, and their antibiotic
      susceptibilities. Between February 1999 and June 2001, 3530 blood samples were
      cultured, of which 915 were found to be positive, and these were further
      investigated in the bacteriology laboratory. Among positive blood cultures,
      coryneform bacteria were identified in 31 (3.4%) isolates. Of these, 16 (51.6%)
      were Corynebacterium jeikeium, six (19.4%) were Corynebacterium striatum, four
      (12.9%) were Corynebacterium amycolatum, two (6.5%) were Cellulomonas species,
      two (6.5%) were Corynebacterium afermentans and one isolate (3.2%) was
      Corynebacterium propinquum. Antibiotic susceptibility tests showed that C.
      jeikeium was resistant to various antibiotics, whereas all isolates were
      susceptible to vancomycin and teicoplanin. This study illustrates the importance
      of taking coryneform bacteria into consideration when culturing blood samples.
      The need to identify the species and determine its antibiotic sensitivity is
      emphasized.

PMID- 12235926
TI  - The effect of the herbal medicine dai-kenchu-to on post-operative ileus.
AB  - Post-operative ileus (PI) is an inevitable adverse consequence of abdominal
      surgical procedures. We performed a randomized study of the effects of the herbal
      medicine dai-kenchu-to (DKT) on 24 patients with PI. Patients received either 15
      g of oral DKT or placebo daily for 14 days. The effects on upper gastrointestinal
      motility, frequency of secondary operation and recurrence of PI were
      investigated. The frequency of surgical operation was significantly lower in
      patients receiving DKT compared with placebo. Oral administration of DKT was
      clinically effective for PI in reducing both the need for further surgery and the
      recurrence of PI.

PMID- 12235927
TI  - The effects of high haematocrit levels on glucose metabolism disorders.
AB  - There has been only limited research investigating the possible association
      between raised haematocrit levels, glucose intolerance and type 2 diabetes. In
      the present study, we explored the association between high haematocrit levels
      and impaired glucose tolerance by performing oral glucose tolerance tests in 46
      patients with chronic obstructive pulmonary disease and no previous history of
      diabetes mellitus or glucose intolerance. A glucose metabolism disorder was
      observed in 12 (26%) patients (type 2 diabetes in six patients and impaired
      glucose tolerance in a further six). There was a significant association between
      high haematocrit levels and the presence of a glucose metabolism disorder, which
      was independent of other risk factors. High haematocrit levels may be an
      independent risk factor for type 2 diabetes and impaired glucose tolerance.

PMID- 12235928
TI  - Evaluation of microcirculation in Buerger's disease using
      201thallium/99mtechnetium macroaggregated albumin scintigraphy.
AB  - In the current study, 10 patients with Buerger's disease (thromboangiitis
      obliterans) and seven control patients with atherosclerosis obliterans (ASO) were
      evaluated for microvascular disturbance. After exercising for 1 min, patients
      were injected with 37 MBq 201thallium (201Tl) intra-arterially, and anterior
      planar images of the feet and whole body images of the lower extremities were
      taken. The same procedure was repeated after 1 week using 185 MBq 99mtechnetium
      macroaggregated albumin (99mTc-MAA). Rectangular regions of interest were drawn
      on the 201Tl and 99mTc-MAA images, and 201Tl/99mTc-MAA uptake ratios were
      calculated. 201Tl/99mTc-MAA ratios of the toes of those with Buerger's disease
      were significantly lower than those of ASO cases, whereas no significant
      difference was found for the lower limbs and feet. These findings may be
      explained by disturbances of microvascular regulation observed in Buerger's
      disease.

PMID- 12235929
TI  - Rate of eating and body weight in patients with type 2 diabetes or
      hyperlipidaemia.
AB  - This preliminary investigation, involving 422 patients, tested the hypothesis
      that rate of eating is associated with obesity in patients with type 2 diabetes
      or hyperlipidaemia at all ages. The patients' eating habits were determined using
      a questionnaire, and the patients were classified as quick, normal or slow
      eaters. The body mass indices of the three groups were compared. The body mass
      indices of the male patients who ate quickly (25.4 +/- 0.2 kg/m2) were
      significantly higher than those of the patients who ate at a normal rate (24.4 +/
      0.3 kg/m2) or slowly (24.1 +/- 0.5 kg/m2). No difference between body mass
      indices in the female groups was found. It was speculated that rate of eating
      affects body weight in male patients with type 2 diabetes or hyperlipidaemia.

PMID- 12235930
TI  - Detection of antimicrobial resistance and extended-spectrum beta-lactamase
      production in Klebsiella pneumoniae strains from infected neonates.
AB  - The present study was designed to determine the antimicrobial resistance and
      extended-spectrum beta-lactamase (ESBL) activities of Klebsiella pneumoniae
      strains isolated from the neonatal intensive care unit of Ataturk University
      Hospital, Erzurum, Turkey. Antibiotic susceptibility of 40 isolates was detected
      by the standard disk diffusion method according to the National Committee for
      Clinical Laboratory Standards Guidelines. The double-disk synergy method was used
      to determine ESBL activity, which is associated with resistance to beta-lactam
      antibiotics. Twenty-four (60%) of 40 K. pneumoniae strains were found to produce
      ESBL. Of the antibiotics tested, meropenem was found to be the most effective
      (100%), and ampicillin the least effective (0%). With the increasing incidence of
      antimicrobial resistance, which poses a clinically significant risk to vulnerable
      patients, it is important that clinical microbiology laboratories have accurate
      and timely information concerning the strains of bacteria present to enable them
      to predict which antibiotics are likely to be effective in treating the
      infections they may cause.

PMID- 12235931
TI  - Primary hydatidosis of the gracilis muscle in a girl.
AB  - Primary muscle hydatidosis is very rare. Rupture and spreading of the cyst
      contents by improper handling may later cause secondary cyst or allergic
      reactions. Preoperative recognition of a hydatid cyst is therefore critical. It
      often presents as a soft-tissue mass, however, and pre-operative recognition of
      this rare entity is clearly difficult. Here, a case of primary hydatidosis
      affecting the gracilis muscle is presented, and the magnetic resonance imaging,
      clinical and pathological findings are described.

PMID- 12235932
TI  - Appendiceal mucocele of mucinous cystadenocarcinoma with a cutaneous fistula.
AB  - We report a novel case of cystadenocarcinoma forming an appendiceal mucocele with
      development of a skin fistula. The patient was a 75-year-old Japanese woman who
      originally presented with a skin ulcer on the right flank (inferior to the ribs
      and superior to the iliac bone) with mucus discharge. The serum concentration of
      carcinoembryonal antigen was elevated (57.4 ng/ml). Ultrasonography and computed
      tomography demonstrated a cystic mass with septations in the right iliac fossa.
      Fistulography from the skin ulceration showed a communication via the fistula to
      the caecum. A right hemicolectomy and enbloc resection of the skin fistula was
      performed. The histological findings revealed a well-differentiated mucinous
      cystadenocarcinoma of the appendix. The patient has been alive for 7 years
      following surgery without any sign of recurrence. This report is of interest as
      it demonstrates that tumour rupture to the extraperitoneal space could result in
      a good outcome by preventing the development of pseudomyxoma peritonei.

PMID- 12235933
TI  - Ruptured and non-ruptured sinus of Valsalva aneurysms: five case studies.
AB  - Between 1987 and 2000, we observed retrospectively a series of five cases of
      surgically treated sinus of Valsalva aneurysms (SVAs) at the Department of
      Cardiovascular Surgery, Ataturk University, Erzurum, Turkey. The mean age of the
      five patients was 32.6 years (range, 18-48 years). Three were male and two were
      female. Aneurysms originated from the right coronary sinus in four patients, and
      from the non-coronary sinus in one. Three aneurysms fistulized to the right
      ventricle, one to the right atrium and the last, originating from the right
      coronary sinus, was non-ruptured. Two aortic insufficiencies, two ventricular
      septal defects, one patent ductus arteriosus and one left ventricular outlet
      obstruction were found as concomitant lesions. All cases were symptomatic.
      Ruptured SVAs were repaired by double approach involving both the chamber and
      aortic root. There was no late mortality either in the hospital or during the
      follow-up period (mean 40.4 months, range 13-66 months). No patient required re
      operation.

PMID- 12235934
TI  - A case of refractory hypothyroidism requiring daily intravenous thyroxine.
AB  - Most patients with hypothyroidism respond to administration of oral thyroxine at
      a maintenance dose of 50-175 micrograms/day. This is the first documented patient
      with post-operative hypothyroidism who required about 10 times the standard dose
      of thyroxine, and whose symptoms only resolved when intravenous thyroxine was
      administered daily. Our findings support the benefits of daily intravenous
      therapy with thyroxine in this case.

PMID- 12235935
TI  - Plucky ideas.

PMID- 12235936
TI  - Sticking to preventive measures.

PMID- 12235937
TI  - Central service. Fine by the Dept. of Ag.

PMID- 12235938
TI  - Supply chain heads speak out [interview by Robert Neil].

PMID- 12235939
TI  - Stats. U.S. market for nonwoven medical apparel.

PMID- 12235940
TI  - Non-punctual patients: planning for variability in appointment arrival times.
AB  - Tighter competition and rationed resources place a premium on health clinic
      management of patient arrival times to maximize smooth workflow dynamics and
      consistency in patient processes. Early efforts to analyze patient arrival
      characteristics relied on assumptions that may have been too simplistic. For
      instance, it was assumed that a scheduled patient's arrival was likely to fit a
      bell-shaped curve in terms of being early, late, or on time and that any one
      patient's likelihood of being "on time" was purely a random event. However, our
      analysis of patient arrival times, obtained from detailed workflow observations
      in nine community clinics, indicates that the likelihood of a patient arriving
      early, late, or on time is neither entirely random nor does the pattern of
      arrivals fit a bell-shaped curve. Rather, patients tend to arrive in "clumps,"
      possibly due to factors such as traffic patterns and parking availability. These
      findings are important with respect to 1) clinic practice management, 2)
      scheduling optimization strategies, and 3) computer simulation and analysis of
      clinic processes.

PMID- 12235941
TI  - Has managed care failed? The answer is: yes and no.
AB  - The managed care industry initially seemed to bring health care cost in line with
      general inflation and growth in the economy. More recently, it has failed to do
      so. This article discusses the background and the trends that have affected
      managed care's ability to provide high-quality, affordable and accessible care.
      In many cases, savings have come principally from pricing and contracting
      strategies rather than a revamping of the delivery of care. Presented are options
      to provide more efficient and cost-effective care based on actual models.

PMID- 12235942
TI  - Telemedicine: an overview.
AB  - Telemedicine involves the transfer of medical data for use in diagnosis,
      treatment and education. The interaction may involve two-way live audio and video
      visits between patients and medical professionals, sending patient monitoring
      data from the home to a clinic or transmitting patient images and medical file
      from a primary care provider to a specialist. Telemedicine is already widely used
      in radiology, cardiac monitoring and other forms of remote patient monitoring and
      in targeted population groups such as correctional care populations, the military
      and veterans' health care.

PMID- 12235943
TI  - Contributory negligence.
AB  - The doctrine of contributory negligence evolved from 19th century economic legal
      policy seeking to protect America's fledgling industries from liability for
      injuries resulting from their activities. These policies resulted in an anti
      claimant environment that made it difficult for any plaintiff, including
      malpractice plaintiffs, to recover for their injuries. Since the onset of the
      20th century, courts, spurred by state and federal legislative acts, have become
      more even-handed, and contributory negligence has become a limited defense in
      malpractice cases. This article defines some of the situations where courts have
      found that patient's actions have barred plaintiff recovery because of
      contributory negligence and offers the limited prediction that contributory
      negligence may be on the verge of once again becoming a major malpractice
      defense.

PMID- 12235944
TI  - Preparing your medical practice for disaster.
AB  - In the wake of the September 11, 2001 World Trade Center terrorist attack,
      practices should seriously consider having a sister plan in effect. Admittedly,
      catastrophes that interrupt medical practice function are infrequent, but they do
      arise at a statistically predictable rate. This article provides an outline of
      the relatively simple and common steps that practices can establish to cope with
      emergency situations.

PMID- 12235945
TI  - Inaccessible information is useless information: addressing the knowledge gap.
AB  - The burdens of increasing information overload, time constraints, and the high
      human and financial costs of medical error, mean that doctors cannot practice
      high quality evidence-based medicine without the aid of decision support systems
      at the point of care. The physician's role is to formulate a management plan
      based on clinical judgment, the patient's unique circumstances and preferences,
      and the best available evidence. Clineguide is a clinical knowledge system that
      will integrate into the workflow to improve patient outcomes, reduce variability
      of care, and promote efficiency in the health care process. This article
      discusses some of the issues surrounding the provision of rapid, accurate, and
      accessible information to health care professionals.

PMID- 12235946
TI  - Firm but fair policies for staff vacations and holidays.
AB  - Paid holiday and vacations are a wonderful employee benefit for your staff.
      However, without some firm policies in place that anticipate and avoid problems,
      holidays and vacations can backfire in a medical practice and become a source of
      problems both for the practice and for the staff. This article provides concrete
      tips for reducing vacation and holiday conflicts and particularly for structuring
      a firm-but-fair vacation policy for new employees. It provides guidance for solo
      practitioners' vacation scheduling and offers a list of the most common paid
      holidays in professional practices today. In addition, this article offers
      answers to common holiday and vacation scheduling questions such as how to handle
      holidays that fall during a vacation and weekend holidays. Finally, this article
      offers specific advice for making the December holiday season a pleasant and
      trouble-free one for your staff.

PMID- 12235947
TI  - How to put your problems in order.

PMID- 12235949
TI  - Ten things to do when investigated by regulatory or government agencies.
AB  - Physicians may become the object of investigation by a variety of regulatory and
      governmental bodies. This article outlines an approach to responding to inquiries
      by such agencies in ten steps. It emphasizes the physician's right to remain
      silent, to defer responses and to obtain legal counsel.

PMID- 12235948
TI  - Supreme Court decisions on benefits and employment law issues.

PMID- 12235950
TI  - Counting to 15: who qualifies as an employee?

PMID- 12235951
TI  - Computer briefs. Last mile broadband: the experiment.

PMID- 12235952
TI  - Are you a team leader? An approach to team building.

PMID- 12235953
TI  - General business theory applied to the physician's practice.
AB  - In the pursuit of clinical excellence in today's competitive medical market
      place, practice managers--clinical or non-clinical--can loose sight of standard
      management and business principles that are key to success. Also, at times
      individuals are hesitant to identify a physician practice as a 'business,'
      preferring to see it as a social good. Still, it is a business--perhaps dealing
      with a product that is a social good, but still, a business. And, as such,
      benefits can be derived from a review of business management theory. This article
      provides a brief review of such theory and also illustrates how to apply this
      theory to the physician's practice. Key factors in building a successful business
      will be discussed and applied to the clinical practice, such as resource
      maximization, rate of return and product mix synergy. Some tools to assist the
      reader in analyzing their practice will also be provided, such as the RVU
      Analysis and the Ratio of Service Analysis.

PMID- 12235954
TI  - Recent advances in implantable cardioverter defibrillator systems.
AB  - The usefulness of the implantable cardioverter defibrillator (ICD) for the
      prevention of sudden cardiac death caused by ventricular tachyarrhythmias has
      been proven by several international randomized multi-center clinical trials.
      Recent advances in medical technologies, such as size reduction and the
      functional improvements of the device, have resulted in relatively easy
      implantation. As a result, the number of ICD recipients has been rapidly
      increasing and the indications for ICD implantation have been expanding. Dual
      chamber ICDs offer improved tachyarrhythmia detection algorithms such as
      discrimination of supraventricular arrhythmias. In Europe and the United States,
      biventricular ICDs are now available for the treatment of congestive heart
      failure associated with ventricular tachyarrhythmias. Although the incidence of
      inappropriate shock by ICDs is decreasing, inappropriate discharges of ICDs and a
      declining quality of life are still problems.

PMID- 12235955
TI  - [A new medical education using a lung sound auscultation simulator called "Mr.
      Lung"].
AB  - We developed a lung sound auscultation simulator "Mr. Lung" in 2001. To improve
      the auscultation skills of lung sounds, we utilized this new device in our
      educational training facility. From June 2001 to March 2002, we used "Mr. Lung"
      for our small group training in which one hundred of the fifth year medical
      students were divided into small groups from which one group was taught every
      other week. The class consisted of ninety-minute training periods for
      auscultation of lung sounds. At first, we explained the classification of lung
      sounds, and then auscultation tests were performed. Namely, students listened to
      three cases of abnormal or adventitious lung sounds on "Mr. Lung" through their
      stethoscopes. Next they answered questions corresponding to the portion and
      quality of the sounds. Then, we explained the correct answers and how to
      differentiate lung sounds on "Mr. Lung". Additionally, at the beginning and the
      end of the lecture, five degrees of self-assessment for the auscultation of the
      lung sounds were performed. The ratio of correct answers for lung sounds were
      36.9% for differences between bilateral lung sounds, 52.5% for coarse crackles,
      34.1% for fine crackles, 69.2% for wheezes, 62.1% for rhonchi and 22.2% for
      stridor. Self-assessment scores were significantly higher after the class than
      before. The ratio of correct lung sound answers was surprisingly low among
      medical students. We believe repetitive auscultation of the simulator to be
      extremely helpful for medical education.

PMID- 12235956
TI  - [Peer education by medical students in a public health course].
AB  - Sex education by peers is becoming popular in Japan. To improve youth's
      reproductive health by continuous peer education and to encourage medical
      students to obtain the methodology necessary for health promotion, we started
      peer sex education by medical students in the annual public health course. One
      junior high school and one senior high school in Kitakyushu City in Japan asked
      medical students to conduct peer sex education classes at their schools. Medical
      students planned and carried out these classes based on the results of a
      questionnaire that they gave to the junior high school and senior high school
      students before the peer education. After the class, the students' responses to
      the class were investigated by another questionnaire. In this questionnaire, over
      90% of the students answered that they were interested in talking about sexual
      issues with medical students. As for the medical students, they said that they
      could understand better the methodology of health promotion and also gained
      confidence by this experience. We will continue to carry out peer education in
      the medical school's public health course, and we intend to research further how
      junior high school and senior high school students' sexual behavior may change in
      the future.

PMID- 12235957
TI  - [Toxicity of dichloropropanols].
AB  - A rare outbreak of acute hepatic damage in workers exposed to dichloropropanols
      was reported in 1992. As there are no detailed reports of dichloropropanols
      (DCPs) toxicity and its mechanism, we reviewed the toxicity of dichloropropanols
      using our results. 1) A marked elevation of serum AST and ALT with massive
      necrosis of the liver was noted in the 1/2 x, the 1 x and 2 x LD50 (0.149 mg/kg)
      of 1, 3-dichloro-2-propanol(DC 2 P). Hepatic malondialdehyde level was
      significantly increased, and associated with a decrease in liver glutathione S
      transferase activity and reduced glutathione content. It is suggested that the
      free radical is associated with DCPs. 2) A reduction of leukocytes, platelets and
      fibrinogen, and prolonged prothrombin time were observed in the 1 x LD50 of DC 2
      P. 3) In the CA1 area of the hippocampus, inhibition of population spikes was
      reduced by the 1 x LD50 of DC 2 P. This research was completed with the
      assistance of several other papers concerning dichloropropanols toxicity.

PMID- 12235958
TI  - [Regulation of bone mass for skeletal loading].
AB  - Skeletal loading plays an important role in the maintenance of bone mass, bone
      shape and bone strength. Skeletal unloading, such as during space flight and long
      term bed rest, induces bone loss in loaded bones in humans. The
      mechanotransduction system in bone tissue is not fully elucidated. Our
      observations demonstrate that generation of nitric oxide through inducible nitric
      oxide synthase is essential for the stimulation of bone formation upon mechanical
      reloading, and that disruption of p53 gene in response to 1-week unloading does
      not result in reductions in bone volume and bone formation. It should be
      significantly helpful for our understanding of various skeletal disorders to
      clarify the mechanism underlying regulation of bone mass after skeletal loading
      and unloading.

PMID- 12235959
TI  - [Regulation of immune responses by prostaglandin].
AB  - Prostaglandin (PG), an arachidonic acid metabolite produced by various cell
      types, regulates a broad range of physiological activities, and maintains the
      local homeostasis. PGE2, one of the PGs, is produced by the action of the enzyme
      PGE synthase and cyclooxigenase (COX) on arachidonic acid liberated from the
      membrane phospholipid by phospholipase A2 (PLA2). In the immune system, PGE2 is
      mainly produced by antigen presenting cells such as macrophages and dendritic
      cells. PGE2 regulates immune responses, for example, the production of cytokines
      and chemokines and the expression of cytokine receptors and cell surface
      molecules, and the main action is mediated by intracellular accumulation of
      cyclic AMP via the activation of adenylate cyclase. The main function of PGE2 in
      the immune system is the suppression of Th1 activation and the enhancement of Th2
      activation. Therefore, in this paper, PGE2, a pivotal factor in the pathogenesis
      of Th1/Th2-related diseases, is highlighted.

PMID- 12235960
TI  - [Immunotherapy of gliomas].
AB  - There has been little change in the average survival of patients with malignant
      glioma these past two decades, despite extensive treatment including surgical
      resection, radiotherapy and chemotherapy. Immunotherapy has attracted the
      attention of many investigators as a new adjuvant therapy, but early approaches
      were largely unsuccessful. This seems to have been related to the immunological
      microenvironment within the central nervous system in which the blood brain
      barrier exists, and where no dendritic cells, potent antigen-presenting cells,
      are distributed. Furthermore, the immunobiological characters of glioma, which
      have many mechanisms to escape host's immunological surveillance, are the reason
      for the difficulty of immunotherapy. However, the modern advanced understanding
      of immunology and molecular biology has yielded novel immunostimulatory
      strategies such as immunogene therapy and dendritic cell manipulations, which
      have caused dramatic preclinical results in glioma models. Although definitive
      clinical results and solutions to side effects remain to be seen, immunotherapy
      shows great promise for the future.

PMID- 12235961
TI  - [A survey of public health nurses regarding their awareness of the abilities,
      skill and knowledge necessary to fulfill an occupational health nurse's role, and
      proposal of a new curriculum for occupational nurse specialists at the master
      level].
AB  - The areas of conduct and professional roles in occupational health nursing in
      Japan has not been defined as yet, even though occupational health nurses have
      contributed to implementing jobs related to the health examination in workplaces
      every year. We surveyed public health nurses regarding their awareness of the
      abilities, skills and knowledge necessary to fulfill an occupational health
      nurses' role. When answering, they became aware of deficiencies in their
      abilities, skills and knowledge. This was particularly true in counseling, health
      assessment skills and management abilities, specialized knowledge of occupational
      safety and health, ergonomics and environmental health. We propose a curriculum
      at the master level for occupational health nurse specialists with reference to
      the core curriculum for occupational and environmental health nursing in the USA.

PMID- 12235963
TI  - [Successful hybrid therapy combined with oral bepridil and ICD in a patient with
      amiodarone refractory life-threatening ventricular tachyarrhythmia associated
      with ischemic cardiomyopathy].
AB  - A 68-year-old man was admitted to our hospital for the treatment of angina and
      ventricular tachyarrhythmia. A coronary and left ventricular angiography showed
      coronary artery disease and ischemic cardiomyopathy with severe left ventricular
      dysfunction. A percutaneous transluminal coronary angioplasty was performed
      successfully in the right coronary artery and his angina symptoms disappeared.
      However, ventricular tachycardia (VT)/ventricular fibrillation (VF) occurred
      spontaneously and converted to sinus rhythm with direct current shock (300 J).
      Oral amiodarone (200 mg/day) and continuous intravenous infusion of nifekalant
      and lidocaine were started. In addition, a dual chamber implantable cardioverter
      defibrillator (ICD) for his VT/VF was implanted. However, VT/VF occurred
      repeatedly after discontinuation of nifekalant. After the administration of
      bepridil (200 mg/day), VT/VF was completely prevented without nifekalant
      administration. The hybrid therapy with ICD and oral bepridil is very useful for
      the treatment of amiodarone resistant ventricular tachyarrhythmia.

PMID- 12235962
TI  - [Occupational physician's role regarding return to work of workers with acquired
      disability].
AB  - Occupational physicians are expected to play important roles in helping workers
      with an acquired disability return to work. However, the key elements to develop
      a successful program to help these workers return to work are still unclear. In
      this study, we searched the literature referring to occupational physicians' role
      in the return-to-work process of the workers with acquired disability. Many of
      these studies mentioned the following; occupational physicians should start co
      operating with the treating physician right after the appearance of the
      disability and exchange medical and occupational health information with each
      other. When a disabled worker wishes to return to work, the occupational
      physician in charge should carefully evaluate his/her work ability, and fitness
      for the work. We also performed a hearing survey at 15 diverse institutions and
      organizations that are generally aimed at promoting employment, social welfare
      and medical service for disabled persons located in at least a 5 million
      population prefecture in Japan. Among them, the Local Occupational Center for the
      Disabled functions as the practical gateway for employment, and the Health and
      Welfare Center is the principal window for the social welfare of the disabled.
      However, their services are sometimes limited to only those who have become
      jobless and not for those returning to their original work. We considered that
      occupational physicians should also communicate positively with the organizations
      to promote successful returning of the workers with acquired disability to their
      former work.

PMID- 12235964
TI  - Updated treatment guidelines for bipolar disorder: key medications.

PMID- 12235965
TI  - The healing power of music. Interview with Trey Forbes. Interview by Shirley A.
      Smoyak.

PMID- 12235966
TI  - Premature menopause and self-concept disjunctions. A case for crisis management.
AB  - 1. Surgically or chemically induced premature menopause is a life transition
      characterized by a situational crisis superimposed on a developmental crisis. 2.
      After surgically or chemically induced premature menopause, women's self-concept
      shifts and evolves through an interactive or relational process. 3. Nurses can
      use crisis management to increase women's understanding of the physiological and
      psychological dimensions of premature menopause, facilitate their links with
      community support systems, and strengthen their existing social networks. 4.
      Effective crisis intervention approaches include structuring, verbalizing,
      clarifying, normalizing, and supporting.

PMID- 12235967
TI  - Mastering group leadership. An active learning experience.
AB  - Leading therapeutic groups is an underused but viable treatment role for nurses
      in all specialty areas. A dynamic psychoeducational group model provides
      structure as nurses invest and collaboratively participate to actively learn the
      group leader role. this article highlights the sequencing of instruction of group
      theory and skills with examples from a baccalaureate nursing curriculum. Samples
      from student journals reveal their growing assimilation of the group leader role
      as learners actively participated in groups, collaborated, and reflected on their
      learning. Examples of creatively adapted group exercises, as well as selected
      nursing group leader interventions, demonstrate group leadership as a skill that
      can increase nurses' repertoire of therapeutic responses. Therapeutic groups are
      both exciting and cost-effective treatment strategies for use with mentally ill
      clients. The skills of an accomplished group leader are transferable from within
      the psychiatric population to working with families, bereavement groups, and
      other client populations, ranging from people with diabetes to survivors of
      catastrophic crises. Group leadership ability complements the management and
      negotiation skills needed in professional nursing roles. When students and staff
      nurses grow in group leadership expertise, clients in various settings will be
      better served with this currently underused treatment option.

PMID- 12235968
TI  - The front lines of domestic violence. Training model for rural EMS personnel.
AB  - 1. Domestic violence is a major public health problem requiring committed,
      coordinated community response. 2. Domestic violence is a significant cause of
      morbidity and mortality for women and children in the United States. 3. EMS
      personnel play a frontline role in the critical response and prevention of
      domestic violence. 4. EMS education and training are requisite for safe,
      effective responses to domestic violence in rural communities.

PMID- 12235969
TI  - Post-war versus post 9/11. Challenges for psychiatric nurses.

PMID- 12235970
TI  - Making quality happen: confronting the external challenges to time and healing
      relationships.

PMID- 12235971
TI  - Achieving career goals through self-evaluation.

PMID- 12235972
TI  - Clinical, financial goals aligned through organizational renewal.

PMID- 12235973
TI  - Benchmarking the billing office.
AB  - Benchmarking data related to human and financial resources in the billing process
      allows an organization to allocate its resources more effectively. Analyzing
      human resources used in the billing process helps determine cost-effective
      staffing. The deployment of human resources in a billing office affects
      timeliness of payment and ability to maximize revenue potential. Analyzing
      financial resource helps an organization allocate those resources more
      effectively.

PMID- 12235974
TI  - Securing revenue through improved managed care compliance.
AB  - Providers risk losing significant revenue when managed care contractual
      obligations go unmet. Contracts should identify claim payment expectations and
      limit administrative responsibilities tied to nonroutine services.
      Multidepartmental cooperation is needed to ensure compliance before, during, and
      after service delivery. Providers should employ technology to manage data related
      to copayment requirements, claims appeals, and patient eligibility.

PMID- 12235975
TI  - A new day for patient financial services.
AB  - The patient financial services (PFS) department plays a crucial role in the
      financial health of a provider organization. Complete, accurate data are a
      competitive advantage. Data should be obtained and validated as early as possible
      in the process of providing a healthcare service. A redefined revenue cycle
      should emphasize interdepartmental collaboration, technology, and patient
      satisfaction. The PFS department should expand its role to emphasize the merging
      of clinical and financial data in support of the organization's goals. PFS
      professionals require educational and career opportunities to fulfill the PFS
      department's expanded role.

PMID- 12235976
TI  - Adopting ideal standards to optimize PFS performance.
AB  - Establishing effective methods for measuring performance can help the patient
      financial services department detect and resolve billing problems, utilize
      resources, and ensure staff accountability. Criteria used to track performance
      should consider all areas that influence accounts receivable (A/R), cash flow,
      days in A/R, and bad debt. Directors should implement mechanisms to track
      appropriate functions on a weekly basis. External standards should be
      incorporated into department goals. Consideration should be given to payer mix,
      upfront collection philosophy, and available resources when comparing one's
      facility with others.

PMID- 12235977
TI  - Success with APCs.
AB  - APCs are having a greater impact on hospital operations and processes than DRGs
      did. Coding must be correct, complete, and compliant. Billing processes should
      catch errors before claims are submitted. Information systems designed
      specifically for outpatient PPS are needed. Organizational changes may include
      naming an APC coordinator and a CDM manager and improving the working
      relationship between the HIM department and the billing office.

PMID- 12235978
TI  - Intermediate sanctions for healthcare organizations.
AB  - Intermediate sanctions legislation requires that tax-exempt providers take steps
      to ensure that their senior staff members are compensated at fair-market value. A
      first-time violation could subject an individual to an excise tax of 25 percent
      of the compensation amount deemed to be excess benefit. Failure to correct the
      violation could subject the individual to an excise tax of 200 percent of the
      excess benefit. Tax-exempt organizations may invoke a rebuttable presumption of
      reasonableness that compensation levels are appropriate. Tax-exempt providers
      should refer to IRS guidance regarding steps to ensuring compliance.

PMID- 12235979
TI  - Quality-of-care issues can create False Claims Act exposure.
AB  - Recent rulings have clarified the False Claims Act's role in addressing failures
      of care. Claims are false if services provided are grossly inadequate. Providers
      can be fined triple the government's payment if they are found in violation of
      the False Claims Act. Providers should be aware of knowing violations of quality
      standards that could lead to False Claims Act exposure.

PMID- 12235980
TI  - Achieving compliance with medical call centers.
AB  - Providers that retain outside call centers for physician referral should take
      steps to ensure compliance with Federal and state antikickback statutes. The
      Federal antikickback statute implicates call centers that offer referral
      services. A Federal safe harbor permits arrangements between participants and a
      referral service under specified circumstances. State antikickback statutes and
      safe harbors may vary from those under Federal law. A provider may not escape
      responsibility for compliance by contracting with call-center vendors. Providers
      and call-center vendors should work together to understand and comply with
      relevant statutes.

PMID- 12235981
TI  - Management by crisis.

PMID- 12235982
TI  - Clinical IS on a budget.

PMID- 12235983
TI  - Investing in health care.

PMID- 12235984
TI  - The Personal Information Protection and Electronic Documents Act: physician
      prescription data and Canadian health system reviews.

PMID- 12235985
TI  - Product liability in the health care setting: the Canadian way.

PMID- 12235986
TI  - Solving the staffing puzzle.

PMID- 12235987
TI  - Software helps clean 'house'.

PMID- 12235988
TI  - Shopping around. Buying best of breed.

PMID- 12235989
TI  - Medication error reduction hopes pinned on CPOE.

PMID- 12235990
TI  - CIOs eye HIPAA's privacy and security rules.

PMID- 12235991
TI  - Lab systems are joining the team.

PMID- 12235992
TI  - Readers' perspective. Sen Ted Kennedy's recently introduced Efficiency in Health
      Care Act.

PMID- 12235993
TI  - How does your practice orient new physician board members?

PMID- 12235994
TI  - Should your practice adhere to a strict dress code? Yea/uniforms look
      professional, save employees money.

PMID- 12235995
TI  - Should your practice adhere to a strict dress code? Nay/diverse settings
      determine appropriate attire.

PMID- 12235996
TI  - MGMA submits comments to CMS on 2003 proposed physician fee schedule.

PMID- 12235997
TI  - What doctors do.

PMID- 12235998
TI  - Go/no go on new clinical technology. What to consider when assessing its
      implementation in the group practice.

PMID- 12235999
TI  - Working smarter. Enhancing physician-nurse team efficiency by managing the
      interface.

PMID- 12236000
TI  - Partly problematic. Part-time physicians present challenges in compensation,
      benefits, partnership.

PMID- 12236001
TI  - End telephone system hassles before they hang up your practice. Choosing a call
      management system.

PMID- 12236002
TI  - Step right this way. Case study: why physicians are signing up to see uninsured
      patients.

PMID- 12236003
TI  - Don't let software training gaps swallow your practice.

PMID- 12236004
TI  - Give and take. Negotiation in health plan contracting.

PMID- 12236005
TI  - Grabbing--or releasing--the brass ring.

PMID- 12236006
TI  - [Parathyroid gland surgery].

PMID- 12236007
TI  - [Cisplatin and carboplatin-induced ototoxicity in children: clinical aspects and
      perspectives for prevention].
AB  - In 70% of the cases of malignant neoplasms in pediatric patients antiblast
      therapy is used. The administration of platinum compounds, Cisplatin (CDDP) or
      Carboplatin (CBDCA), often at high cumulative doses, necessarily implies a
      certain degree of toxicity which normally takes on secondary significance in the
      healing of the child. Among the side effects, early and delayed ototoxicity is
      well known and, in the child, take on particular aspects. While not abandoning
      the treatment of the base pathology, the therapeutic findings, increasingly
      comforting in terms of long-term survival, require more accurate evaluation and
      overall control of the quality of life of these young patients. Since initial
      cochlear damage can be reversible, auditory function must be carefully monitored
      in order to prevent the lesions from becoming permanent, in particular prior to
      the onset of speech. For this reason a retrospective study was made of a group of
      26 children affected by malignant neoplasms all of whom had undergone a
      polychemotherapy protocol with the administration of CDDP in 14 cases and CBDCA
      in 12 cases. All these young patients were monitored with conventional
      audiometry. The presence of different variables (antiblastic drug administration
      schedule, course of the disease, general conditions) only permitted evaluation of
      a single correlation: between auditory function at the end of the treatment (or
      after a few cycles of therapy) and the overall dose of CDDP or CBDCA
      administered. In 16 cases (62%) typical bilateral perceptive deafness was
      detected progressively involving the hyperacute and acute frequencies. The
      finding of hearing loss was significantly greater in the patients treated with
      CDDP (86%) vs. those treated with CBDCA (33%). Moreover, analysis of the results
      showed that, within certain limits, ototoxicity can depend more on individual
      sensitivity to the drug than to the total dose administered. The results confirm
      the well-known ototoxicity of platinum compounds, in particular CDDP. As ever
      improved therapeutic results are achieved in the treatment of malignant neoplasms
      in pediatric patients, greater attention can be paid to the quality of life of
      these young patients after the disease has been healed. Careful monitoring of
      auditory function can be extremely important in the pursuit this objective;
      indeed, this makes it possible to adjust antiblast drug administration,
      particularly in the later stages of treatment, customizing the treatment schedule
      to individual patient sensitivity.

PMID- 12236008
TI  - [Preoperative imaging in chronic otitis surgery].
AB  - High resolution computed tomography (CT) is presently the most accurate technique
      to study the temporal bone. Nevertheless, there is no general agreement about its
      usefulness in pre-operative evaluation of chronic otitis media. Indeed, if we
      rule out some exceptions, CT is not fundamental for diagnosis which can often be
      obtained through an accurate otomicroscopy. The Otology Group in Piacenza applies
      the following absolute indications for pre-operative CT in chronic otitis media:
      1) difficult otomicroscopy evaluation; 2) suspected petrous bone cholesteatoma;
      3) dubious diagnosis; 4) suspect of malformations; 5) review of cases that had
      previously undergone mastoidectomy; 6) suspected intracranial complications
      and/or meningoencephalic herniation (in this case also a magnetic resonance
      imaging must be performed). With the exception of these specific conditions, pre
      operative CT is useless in cases of simple chronic otitis. However, when a
      cholesteatoma is suspected, CT can provide the surgeon, particularly when
      inexperienced, useful, but not indispensable, informations. Pre-operative
      knowledge of these informations can allow a more accurate evaluation of the case,
      with a better planning of the surgical procedure, in order to ensure a more
      specific informed consent. Finally, the Authors point out the fact that surgeon
      must be able to interpret by his own the CT data to have a real advantage by this
      examination.

PMID- 12236009
TI  - [Rhinocerebral mucormycosis: report of a rare case in the head-neck and chest
      area].
AB  - Mucormycosis is a severe fungal disease. It can present in two clinical forms:
      localized or disseminated. The most common, often lethal, form is localized
      rhinocerebral mucormycosis and is associated with diabetes, debilitation and
      immunologic deficiencies. The primary location is generally found in the nasal
      cavity, paranasal sinuses or hard palate. The infective process can extend into
      the orbita, the cavernosus sinus, the pterygium-palatine and infratemporal fossae
      with generation of mycotic emboli that can plug the cerebral arteries and, in
      certain circumstances, can lead to death if it goes untreated. This work
      describes a clinical case of a 76-years-old patient with a previous history of
      alcoholism and glucose intolerance, affected by rhinocerebral mucormycosis with
      extension to the lungs. A general medicine division sent the patient for
      observation by a specialist since, at the time of hospitalization, objective
      testing showed signs of an ulcerating lesion of the alveolar edge of the left
      hemipalate associated with a bilateral pulmonary neoformation suspected to be
      neoplastic. The patient underwent pulmonary and maxillo-facial surgical resection
      and medical therapy. The authors discuss the appropriateness of diagnosis and
      treatment procedures in cases of mucormycosis in association with other
      pathologies, that can complicate the clinical picture, delaying diagnosis and
      treatment. The authors point out the need to perform in a short time an adequate
      medical and surgical treatment of mucormycosis, because of the risk of
      intracranial extension, leading to an increased mortality, even as high as 80%.
      The longer it takes to reach a diagnosis the more radical the surgical treatment
      will need to be.

PMID- 12236010
TI  - [Laryngeal carcinoma associated with congenital tracheobronchomegaly (Mounier
      Kuhn syndrome): a case report].
AB  - Congenital tracheobronchomegaly or Mounier-Kuhn Syndrome is a rare disorder of
      controversial etiology. It is characterized by an abnormal enlargement of the
      trachea and primary bronchi, because of atrophy or absence of their elastic
      fibers and smooth muscles. Such alterations lead to the collapse of the
      respiratory tract during forced exhalation, making expectoration by coughing of
      little use. Subjects with this disorder are, therefore, predisposed to the
      development of phlogistic bronchopulmonary pathologies such as bronchitis,
      emphysema, bronchiectasis and pulmonary fibrosis. The present work reports the
      case of a 65-year-old man suffering from asymptomatic congenital
      tracheobronchomegaly which was unknown until preoperative testing was performed
      (standard chest x-ray, tracheobronchoscopy) following a diagnosis of squamous
      cell carcinoma of the larynx. The patient underwent total laryngectomy and
      bilateral neck dissection without any intra- and postoperative complication. This
      is the first case reported in the literature of an association between laryngeal
      carcinoma and Mounier-Kuhn Syndrome, although a cause-effect relationship between
      the two pathologies cannot be advanced at this time. This paper also reports how
      the patient was managed in terms of anesthesiology and surgical technique, both
      conditioned by the marked tendency for anteroposterior tracheal wall collapse and
      its high reactivity to mechanical insults.

PMID- 12236011
TI  - [Pharyngeal and laryngeal hamartoma: case report].
AB  - In this report a case of laryngeal hamartoma is presented. Macroscopically this
      lesion is quite similar to a tumor but is actually a malformation derived from an
      error in the development of a healthy organ. Histologically, the hamartoma is
      composed of a proportionally abnormal mixture of tissues as compared to what is
      normally present in its anatomic site. The lesion is extremely rare and usually
      appears in the head and neck district, spleen, pancreas, lung and liver. The
      diagnosis is essentially based on histological examination. The treatment of
      choice consists of surgery and periodic follow-up. Differential diagnosis must
      consider other rare neoplasms such as rhabdomyoma and teratoma.

PMID- 12236012
TI  - [History corner. Philipp Bozzini and the endoscope. The origin of the endoscope].

PMID- 12236013
TI  - [Maturation aspects of the auditory apparatus].

PMID- 12236014
TI  - ED managers are planning for smallpox vaccine.

PMID- 12236015
TI  - Assessing trauma patients boosts efficiency.
AB  - By scoring trauma patients before they arrive in the ED, a Maine ED reports
      improved care, fewer problems with on-call physicians, and more efficient use of
      hospital resources. On-call surgeons previously were contacted for all trauma
      cases, but now they are contacted only if scores indicated this is necessary.
      Only a small percentage of trauma patients actually need a surgeon immediately.
      The trauma team is called in before the patient arrives if scores show it is
      needed, but otherwise, the team is not mobilized.

PMID- 12236016
TI  - 'Dirty bomb' threat puts spotlight on unprepared EDs: do you have a plan?
AB  - Almost half of hospitals lack a plan for nuclear terrorism; however, disaster
      management experts say it's not difficult to add this to an existing disaster
      plan. Screen all incoming patients for radiation if a disaster involves the use
      of explosives. Provide staff with training in radiologic monitoring. Use a dirty
      bomb scenario for your next disaster drill.

PMID- 12236017
TI  - [Physiology and pathophysiology of the vascular endothelin system: clinical
      implications].
AB  - The endothelium-derived 21 amino acid peptide endothelin-1 is one of the most
      potent vasoconstrictors. Endothelin-1 exerts its effects upon a variety of
      vascular and non-vascular cells through a direct interaction with specific
      receptors. Beyond its vasoconstrictive action on vascular smooth muscle cells
      endothelin-1 has mitogenic and pro-inflammatory properties. The present review
      deals with current experimental and clinical evidence for the involvement of
      endothelin-1 in several cardiovascular disorders with inflammatory components. We
      further discuss the potential clinical relevance of the endothelin system and
      therapeutical perspectives of anti-endothelin strategies in the treatment of
      cardiovascular disease.

PMID- 12236019
TI  - The risk of recurrent venous thromboembolism.
AB  - Venous thromboembolism (VTE) is a chronic rather than acute disease. After
      withdrawal of secondary thromboprophylaxis, many patients will experience a
      subsequent episode of thrombosis. Of these patients, approximately 5% will die
      from pulmonary embolism. The risk of recurrent VTE depends on the number of risk
      factors and their severity. High-risk patients, i.e. those with a natural
      coagulation inhibitor deficiency, recurrent thrombosis, active cancer, the lupus
      anticoagulant or compound clotting defects most probably benefit from indefinite
      oral anticoagulation. In these patients the risk of bleeding due to anticoagulant
      treatment seems to be outweighed by the risk of VTE. Patients with
      hyperhomocysteinemia or high factor (F) VIII plasma levels are also at an
      increased risk of recurrence. The optimal duration of secondary
      thromboprophylaxis in these patients is currently under investigation. Patients
      with the heterozygous F V Leiden mutation or the G20210A mutation in the F II
      gene do not require extended anticoagulation since their risk of recurrence is
      similar as in patients without the aforementioned mutations. Patients with VTE
      secondary to surgery or trauma have a relatively low risk of recurrence. In these
      patients short-term secondary thromboprophylaxis (6 to 12 weeks) is justified
      whereas patients with a first episode of spontaneous VTE should be treated with
      oral anticoagulants for a longer period of time (3 to 6 months).

PMID- 12236018
TI  - [Current status of endovascular therapy in the femoropopliteal vascular segment
      in chronic peripheral arterial occlusive disease].
AB  - Technical success of endovascular measures in the femoropopliteal region has
      increased since the introduction of new technology (hydrophilic guide-wires,
      stents, stent grafts) in the last decade to rates of more than 90%. If the
      initial revascularization--even of long segment occlusions--is successful, the
      modern armamentarium of interventional radiology enables to keep the vessel open
      acutely. Evidence, that the immediate success of revascularization leads to a
      continuous improvement of the clinical symptoms, measured by clinically relevant
      end points (e.g. improvement of walking distance, increase of limb salvage,
      increase of survival), has yet to be shown. Several prospective randomized trials
      demonstrated improvement of walking distance after one year follow-up, but not
      after two years follow-up in patients with chronic femoropopliteal obstructions,
      who were treated with PTA compared to walking exercise only. The only two
      prospective randomized trials comparing vascular surgery and endovascular therapy
      for femoropopliteal obstructions could not demonstrate any advantage of one of
      the two modalities in patients with claudication or critical ischemia. The
      transatlantic consensus document (TASC) recommends PTA as therapy of choice in
      the femoropopliteal arteries only for single stenosis < 3 cm and does not
      recommend primary stenting. In order to evaluate endovascular therapy in the
      femoropopliteal region outcome studies are needed, which carefully assess
      clinically relevant end points like improvement of walking distance, limb
      salvage, and survival, but also disease specific quality of life evaluations.
      Several meta-analyses, performed in recent years, have demonstrated that
      endovascular therapy has a definite role in the femoropopliteal segment. However,
      the particular role has to be evaluated for the individual clinical case in the
      light of case-specific findings and symptoms.

PMID- 12236020
TI  - [Endovascular therapy of aneurysms of the abdominal aorta: report of 4,291
      patients of the Eurostar Register].
AB  - BACKGROUND: The Eurostar project is a multicentred database of the outcome of
      endovascular repair of infra-renal aortic aneurysms. From 1996 to March, 2002,
      113 European centres of vascular surgery have contributed. The purpose of this
      article is to review the medium term (up to 7 years) results of endovascular
      aneurysm repair as reported to Eurostar. PATIENTS AND METHODS: Patients intended
      for endovascular aneurysm repair were notified to the Eurostar Data Registry
      Centre before treatment in order to eliminate bias due to selective reporting.
      The following data was collected on all patients: (1) their demographic details
      and the anatomical characteristics of their aneurysms, (2) details of the
      endovascular device used, (3) procedural complications and the immediate outcome,
      (4) results of contrast enhanced CT imaging at 1, 3, 6, 12, 18 and 24 months
      after operation and at yearly intervals thereafter, (5) all adverse events. Life
      table analysis was performed to determine the cumulative rates of: (1) death from
      all causes, (2) secondary intervention. RESULTS: By March 2002, pre- and
      postoperative data of 4291 patients had been registered. The median duration of
      follow-up was 12 mo (range 0-96). Successful deployment was achieved in 97.8% of
      the patients with a perioperative (30 day) mortality of 2.4%. Early conversion to
      open repair occurred in 1.3%. Late rupture of the aneurysm occurred in 35
      patients. The significant factors were endoleaks, graft migration and kinking.
      Late conversion to open repair occurred at an annual rate of approximately 2%.
      Risk factors (indications) for late conversion were endoleaks, graft migration
      and kinking. CONCLUSIONS: Endovascular repair of infra-renal aortic aneurysms
      using the first and second-generation devices that predominated in this study is
      associated with a risk of early or late failure of 3% per year, based upon an
      analysis of observed primary endpoints of rupture and conversion.

PMID- 12236021
TI  - Evaluation of clinical tests to assess perfusion in chronic critical limb
      ischemia.
AB  - BACKGROUND: Evaluation of macro- and microcirculatory tests to confirm diagnosis,
      and recognize perfusion changes in chronic critical limb ischemia (CLI). PATIENTS
      AND METHODS: Forty-two consecutive patients with CLI examined at the University
      Hospital Bern, with 21 included in this prospective follow-up analysis. Patients
      underwent serial clinical examinations, and assessment of the macro- (ankle
      arterial pressure [AP], great toe pressure [TP], oscillography) and
      microcirculation (transcutaneous partial oxygen pressure [tcPO2] recumbent,
      sitting, O2-inhalation; capillary microscopy) at baseline, 6 weeks after
      revascularization (group 1; [n = 11]), or after 10 weeks in patients unsuitable
      for revascularization (group 2; [n = 10]). Clinical improvement was considered to
      indicate increased perfusion. RESULTS: Eleven patients with revascularization
      (11/11), and 2 without revascularization (2/10) showed clinical improvement. AP
      measurements were not reliable or feasible in 9 (43%), TP in 4 patients (19%),
      respectively. All measurable pressures were in accordance to clinical course.
      Oszillography gave a moderate perception of perfusion changes. Baseline tcPO2
      levels were critical (< 30 mmHg) in all 21 patients, whereas follow-up gave poor
      correlation with the clinical course. Reliability to detect perfusion changes
      increased by adding provocation manoeuvers in patients with clinical improvement
      (39% [5/13] recumbent, 77% [10/13] sitting, 85% [11/13] O2-inhalation). Capillary
      microscopy revealed a relevant pathology at the forefoot level in all patients
      with feasible examinations (18/21), and significant improvements according to the
      clinical course in 92% of patients (12/13). CONCLUSIONS: TP measurements
      represented most reliable test to confirm diagnosis and disclose improved
      perfusion in CLI. TcPO2 measurements in recumbent position gave unreliable
      results, improved by provocation manoeuvers. Capillary microscopy was reliable,
      but time consuming and limited by anatomical restrictions.

PMID- 12236022
TI  - High resolution contrast enhanced MR-angiography of the hand arteries:
      preliminary experiences.
AB  - BACKGROUND: In contrast to magnetic-resonance-angiography (MRA) of the peripheral
      vessels of the lower extremity, which gains more and more clinical application,
      MRA of the hand arteries is still exceptional. Our objective was to introduce an
      appropriate protocol for high resolution contrast-enhanced MR-angiography of the
      hand arteries. PATIENTS AND METHODS: 7 healthy volunteers and 13 patients with
      suspected hand artery obstructions underwent MRA. The examinations were performed
      on a 1.5 T system equipped with a flexible surface coil. A modified 3D-gradient
      echo sequence was used. Criteria for image analysis were the overall image
      quality, vessel visibility and the timing of the contrast material bolus.
      RESULTS: In the volunteer group delineation of the superficial or deep palmar
      arch, common palmar digital arteries and of the proximal and middle segments of
      the digital arteries was possible. No pathologic findings were seen in the
      volunteer group. In 10 patients MRA revealed pathologic findings. In 9
      examinations bolus-timing was correct, 7 examinations showed incomplete arterial
      enhancement, 4 examinations showed venous overlay. CONCLUSIONS: Contrast enhanced
      MR-angiography of the hand arteries in the described technique is a promising
      method. Compared to intraarterial digital subtraction angiography (IA-DSA) MRA
      still has limitations concerning spatial and temporal resolution. For clinical
      evaluation comparative studies with IA-DSA are necessary.

PMID- 12236024
TI  - Predilection of hemolytic anemia-associated leg ulcers for the medial malleolus.
AB  - BACKGROUND: Ischemic ulcers are usually found above the lateral, and venous
      stasis ulcers at the medial malleoli. Leg ulcers occur in at least 25% of sickle
      cell disease (SSD) patients in clinic populations, usually in the malleolar
      region. The function of the large leg veins in most SSD patients is unimpaired.
      PATIENTS AND METHODS: We determined leg ulcer location in 41 sickle cell anemia
      (SS), and 4 sickle-beta 0 thalassemic patients with longstanding chronic and/or
      recurrent leg ulceration, and reviewed published reports of leg ulcers in
      hereditary spherocytosis and thalassemias. RESULTS: Of the 57 legs of the 45 SSD
      patients with only 1 ulcer, 42 (74%) were medial and 15 lateral. The difference
      was significant (p < 0.001). Of patients with only a single ulcer, 22 were medial
      and 4 lateral. Of 15 reported patients with leg ulcers related to spherocytosis
      or thalassemia, 20/24 (83%) ulcers were medial. CONCLUSIONS: The medial malleoli
      are the most common site of leg ulceration in SSD and in other chronic hemolytic
      anemias. This suggests that stasis may play a role in the leg ulceration
      associated with chronic hemolytic anemia.

PMID- 12236023
TI  - The efficacy and safety of a coumarin-/troxerutin-combination (SB-LOT) in
      patients with chronic venous insufficiency: a double blind placebo-controlled
      randomised study.
AB  - BACKGROUND: The objective was to evaluate the oedema-protective effect of a
      vasoactive drug (coumarin/troxerutin [SB-LOT]) plus compression stockings in
      patients suffering from chronic venous insufficiency after decongestion of the
      legs as recommended by the new guidelines. PATIENTS AND METHODS: 231 patients
      were randomly assigned medical compression stockings plus SB-LOT (90 mg coumarin
      and 540 mg troxerutin per day) or medical compression stockings plus placebo for
      the first 4 weeks and SB-LOT or placebo for the second 12 weeks of the study. The
      primary efficacy endpoint was the lower leg volume measured by well-established
      water plethysmometry. RESULTS: 226 patients were evaluated. After ceasing
      compression stockings, an edema protective effect was detected in the SB-LOT
      group but not in the controls. Recurrence of leg volume increase was by 6.5 +/-
      12.1 ml and by 36.7 +/- 12.1 ml in the SB-LOT and placebo group, respectively (p
      = 0.0402). The local complaint score and general aspects of quality of life were
      also superior for the SB-LOT-group (p = 0.0041). Significant differences were
      also observed with regard to clinical global impression and therapeutic effect.
      No serious adverse drug reaction or clinically relevant impairment of laboratory
      parameters occur. CONCLUSION: This study confirms the oedema-protective effect of
      SB-LOT in chronic venous insufficiency and provides a treatment option for
      patients who discontinue compression after a short time.

PMID- 12236026
TI  - Acute intramural haematoma of the coeliac artery.
AB  - The report describes a previously healthy 24-year-old women presenting with acute
      abdominal pain following a hyperextension manoeuvre. The key finding of a
      continuous bruit with systolic and diastolic components in the epigastric region
      subsequently led to the diagnosis of an intramural haematoma of the coeliac
      artery, that caused a subtotal occlusion of the artery. The diagnosis was
      achieved by both colour-coded duplex sonography and magnetic resonance
      angiography. The case shows that a conservative management rather than operative
      reconstruction is justified in an oligo-symptomatic situation with no signs of
      end-organ damage as in this patient.

PMID- 12236025
TI  - Noninvasive tests for risk stratification in major vascular surgery.
AB  - BACKGROUND: The predictive values of noninvasive tests versus perioperative
      cardiac events in patients undergoing major vascular surgery has not been
      definitively established. PATIENTS AND METHODS: According to clinical markers and
      left ventricular function at rest, 188 patients were assigned to the following
      groups: 40 low, 115 moderate and 33 high risk. They were then randomly submitted
      to dipyridamole (n = 64), dobutamine (n = 63) stress echocardiography and
      dipyridamole perfusion scintigraphy (n = 61). RESULTS: No events were observed in
      low-risk patients, whereas 12 (10.4%) and 8 (24%) events in moderate- and high
      risk categories occurred, respectively. Only the high-risk category, as a
      predictive variable, was significantly related to the onset of cardiac
      complications (p < 0.05). A positive dipyridamole/dobutamine stress test was
      related to cardiac events, but multivariate analysis showed that only severity
      and extent of ischemia were the best predictors of events (p < 0.01 for
      dipyridamole and p < 0.005 for dobutamine). The presence of reversible, but not
      fixed, perfusion defects at scintigraphy was significantly related to
      perioperative events; at multivariate analysis, only > 3 reversible perfusion
      defects represented a strong predictor of events (p < 0.05). CONCLUSIONS: Among
      subjects undergoing major vascular surgery, severity and extent of ischemia
      during dipyridamole/dobutamine stress echocardiography and presence of > 3
      reversible perfusion defects are strong predictors of cardiac events,
      particularly in moderate-risk category of patients.

PMID- 12236027
TI  - [Pseudoaneurysm of the right gastric artery].
AB  - Mostly, the rare pseudoaneurysm of the right gastric artery is a complication of
      a pancreatitis. Clinical findings might be normal, but there is also a
      hemorrhagic shock in case of rupture. Diagnostic procedures are ultrasound,
      colour doppler ultrasound, computertomography and angiography for treatment.
      While endoscopy does not enable a therapeutic approach, interventional radiology
      with transcatheter embolization is a modality, which can be performed fast, sure
      and without complications. In case of an intractable acute hemorrhage the
      embolization is an alternative to surgical emergency.

PMID- 12236028
TI  - Recurrent exercise induced subclavian vein thrombosis in a conductor.
AB  - We present a case of a young male patient with recurrent subclavian vein
      thrombosis due to conducting after prior successful thrombolytic therapy.
      Musculoskeletal problems are common among musicians. A thoracic outlet syndrome
      associated to a profession induced thrombosis in a musician has not been
      described before. Surgical removal of the first rip can prevent recurrent
      thrombotic occlusion of the subclavian vein, but was not performed in this
      patient. Considering the specific situation of a young musician there is no
      information whether surgical or conservative treatment is suitable to allow a
      successful career as an active musician.

PMID- 12236029
TI  - [Nosocomial infections at a pediatric age].
AB  - The overall incidence of nosocomial infections in children ranges from 2.3% to
      12.6%. Even if there are great variations among data in literature, most authors
      agree that nosocomial infections are less frequent in children than in adults.
      Differences between these two populations concern anatomical sites of infection
      and microrganisms: in children, most frequent are gastrointestinal infections (10
      35%), respiratory infections (5-30%) and bacteremia (10-23%); Gram positive
      bacteria account for 31-50% of infections, Gram negative for 23-35% and viruses
      for 22-27%. All these percentages change enormously depending on the type of
      department and child age. Because of increasing rates of resistance to
      antimicrobial agents, it is important to identify the main infectious agents and
      their sensibility, considering carefully when to give antibiotic therapy and what
      drug should be chosen.

PMID- 12236030
TI  - New strategies for the diagnosis and follow-up of vesicoureteral reflux.

PMID- 12236031
TI  - [Oral antibiotic therapy: problems and perspectives].
AB  - As all therapies, oral antibiotic therapy has its own scientific rationale.
      Infact, for an optimal oral therapy the drug must be absorbed completely, reach
      the infection site and diffuse in the tissues. It should also remain active for
      as long as possible at the minimal bactericidal level of concentration. It is
      therefore necessary to use drugs with a specific bactericidal action for the
      pathogens in question and that these drugs be administered at right doses for the
      necessary duration so that the infection is eliminated. It is an inappropriate
      therapy that which not only fails to eliminate the infection, but leads to the
      development of resistance, which is an increasingly serious and diffused problem.
      In hospital and at home it is possible to switch from an injected antibiotic form
      to the more practical and less expensive oral form, therefore creating a
      sequential therapy which is better accepted by patients and their families. The
      acceptance of prescribed therapies is an aspect that should never be
      underestimated, especially during the development age. Infact, despite the
      general understanding that unsatisfactory clinical results are a consequence of
      unadequate compliance with therapy, the desire to recover is rarely the same as
      the will to follow such plans, even if the patient expects a quick and full
      recovery. It is therefore necessary to use those therapies which are best
      accepted but always effective in order to avoid legal implications.

PMID- 12236032
TI  - [The use and abuse of antibiotics in childhood].

PMID- 12236033
TI  - [Malignant primary tumors of the liver in childhood].
AB  - Twenty-one children (16 males, 5 females) with malignant primary hepatic tumors
      were admitted to the Pediatric Clinic of the University of Bologna between June
      1973 and July 2001. The diagnosis was hepatoblastoma (HBL) in 16 cases;
      hepatocellular carcinoma (HCA) in 3 cases; undifferentiated sarcoma in 1,
      malignant rhabdoid tumour of the liver in 1. Median age at diagnosis was 1.8 year
      (1 mounth-13 years). As to intrahepatic tumor's extension, patients were
      classified in groups (from I to IV) according to International Society of
      Pediatric Oncology staging. 2 patients were ascribed to group I; 9 to group II; 9
      to group III and I to group IV. At diagnosis 3 pts presented lung metastases.
      Seventeen patients (81%) were treated with surgery, in 11 cases as first approach
      to the tumor. In 10 patients, initially with unresesectable tumor, chemotherapy
      was started first. Drugs used were mostly Cisplatinum or Carboplatinum with
      Doxorubicin. Sussequently 6 patients were submitted to surgery. At a median
      follow up of 12.5 years, 52.3% of patients is alive without disease. This
      percentage rises to 58% taking into consideration only HBL and HCA cases (alive
      11/19). We conclude that excluding metastases at diagnosis (3 deaths), the main
      prognostic factor is resectability and radical surgery: in our experience 4
      patients with unresectable tumor died, as 2 patients with microscopical residual
      after surgery.

PMID- 12236034
TI  - [The role of anti-endomysium and anti-transglutaminase antibodies in the
      diagnosis and follow-up of celiac disease].
AB  - Available, non invasive, serological tests such as the anti-endomysium antibodies
      (EmA) and anti-transglutaminase antibodies (Anti-tTg) has allowed better
      outlining of the clinical presentation as well as the pathogenesis of Coeliac
      Disease (CD). The aim of the study was to evaluate the reliability and
      concordance of EmA and anti-tTg at the diagnosis (T0) of CD and after 12 months
      (T12) of Gluten-Free Diet (GFD). Serum EmA and Anti-tTg were evaluated in 78
      patients aged 6.3 +/- 4.7 SD yrs at diagnosis, in 56 of them at T0 and T12, as
      well as in a control group of 88 children aged 6.9 +/- 3.8 yrs. EmA were
      evaluated by indirect immunofluorescence and Anti-tTg by ELISA. All subjects had
      normal circulating IgA levels. In the control group, EmA and Anti-tTg resulted
      negative in all cases. At T0, 77/78 pts had both EmA and Anti-tTg positive, one
      pt (1.3%) had only EmA positive, demonstrating an overall positive concordance of
      98.7%. At T12, 16 pts (28.6%) had both tests positive, 8 (14.3%) had only Anti
      tTg positive (all of them were no fully compliant to GFD) and 32 (57.1%) had both
      tests negative. The overall concordance at T12 was 85.7%. The concordance between
      EmA and Anti-tTg at T0 is nearly absolute (98.7%). The higher prevalence of
      elevated anti-tTg than of positive EmA at T12 suggests a higher sensitivity of
      anti-tTg following intake of even small amounts of gluten.

PMID- 12236035
TI  - [Normal urinary levels of telopeptide aminoterminal (NTx) of type I collagen in
      healthy term newborns and infants in the first month of life].
AB  - The Authors have studied urinary aminoterminal telopeptide of type I collagen
      (NTx), a bone catabolism marker of recent determination, by an enzyme-linked
      immunoassorbent assay (OSTEOMARK) in 80 urine samples of term healthy infants in
      the first 3 months of life. Highly significant variations have been compared in
      the whole period studied (P = 0.000). Levels of NTx increase significantly from 1
      to 7 days of life, reaching a plateau that is kept until 45th day and then
      significantly decrease until 90th day, when, however, they result higher than the
      values reported in literature concerning older ages. The Authors conclude that
      even this bone catabolism marker is influenced, in the first week of life, by the
      particular phenomenology linked to the neonatal adaptation, and that,
      subsequently, shows a trend strictly linked to the bone turnover modifications
      throughout the faster stage of the growth.

PMID- 12236036
TI  - [Video-assistive minimally invasive surgical procedures in the treatment of
      thyroid in children and adolescents].
AB  - Minimally invasive video-assisted (MIVA) surgery of the thyroid is now widely
      accepted by endocrinel surgeons, especially in adult age. This report describes
      indications, limits, technical aspects and results of MIVA in 10 young patients
      (mean age 16 years, range 11-18) enrolled in a study of 213 patients (mean age 45
      years, range 11-81) operated with this technique, from October 1998 to August
      2001, in the Department of Surgery at the University of Pisa. Young patients were
      submitted to surgery: 8 lobectomies (6 for microfollicular lesions and 2 for
      adenomas functionally autonomous) and 2 total thyroidectomies for papillary
      carcinoma. No case has been converted in "open" surgery and no post-operatory
      complications have been observed. Elective indications of MIVA are the volume of
      the nodule and the istological type. This technique cannot be performed in
      voluminous goiters, in medullary carcinomas and in scarcely differentiated
      carcinomas. Minimally invasive video-assisted surgery of the thyroid, in our
      experience, represents a reliable technique also in pediatric age.

PMID- 12236037
TI  - [Primary megaureter detected during the first year of life. Review of case
      reports in the last 10 years and analysis of prognostic factors].
AB  - AIM: We report our experience in the treatment of primary megaureter discovered
      prenatally or in the first year of life. We also discuss the prognostic role of
      the first diuretic renogram performed immediately after the discovery of the
      megaureter. MATERIAL AND METHODS: 45 patients have been observed since January
      1990 until December 1999, with 54 primary non refluxing megaureters (9 bilateral
      cases); 18 discovered prenatally; 24 detected during a postnatal echographic
      screening of urinary malformations; and 3 symptomatic. All the patients have been
      studied and followed-up with repeated sonograms and diuretic nephrograhis.
      RESULTS: 19 patients underwent surgery, 5 at presentation and 14 early during
      follow up. In this group, 7 patients were operated on because of urinary tract
      infection, 5 had a functional impairment of the involved kidney and 2 presented a
      progressive increase of ureteral size. 29 megaureters have been followed non
      operatively, of these, 6 resolved and 19 improved dilatation, 10 were unchanged
      and 3 cases underwent progressive worsening. Half time clearance (T 1/2)
      calculated during the first diuretic renogram had a favorable prognostic
      significance when the value was under 10', but when the value was above 10' the
      evolution was unpredictable.

PMID- 12236038
TI  - [The efficacy of surgical treatment of hypospadias: analysis of hospital data
      from Lazio region during the three year period (1996-8)].
AB  - INTRODUCTION: The aim of this study is to assess effectiveness of surgical
      treatment for hypospadia in the Regione Lazio (Italy). Hospital discharge data
      concerning surgical repair of hypospadia between 1996-1998 were analysed in order
      to: 1. estimate the trend of demand for hypospadia treatment; 2. correlate
      clinical results with the type of Surgical Unit of admission (general pediatric,
      urological, plastic); 3. correlate surgical results with the workload of the
      Unit; 4. quantify the general risk of a secondary treatment. METHODS: The source
      of data was the Hospital Information System of the Regione Lazio. Cases have been
      grouped according to Health District, age at first operation, interval to re
      hospitalization after the first treatment for hypospadia. RESULTS: Age at first
      operation progressively declined in the last years. The annual risk of
      readmission and reoperation after the first surgical treatment, calculated on a
      group of 521 cases in 1996, are respectively 6.6% and 5%. CONCLUSIONS: The demand
      for hypospadia surgery in children was, as expected, stable in the time. However,
      a tendency to an earlier correction has been observed, mainly in the first and
      second year of life. Nearly all (99%) of the surgery for hypospadia in the
      Regione Lazio is performed in four hospitals; one of them accounts for three
      quarters of the workload. During the observed period a progressive reduction of
      hospital stay was seen. In the hospital with the best results in term of surgical
      efficiency, a significant number of patients is treated on a Day Surgery basis.
      Institutions treating less than 50 cases per year show a significantly high rate
      of re-hospitalisation within 12 months.

PMID- 12236039
TI  - [E-mail pediatric consultation].
AB  - Widespread diffusion of the Internet and of electronic mail allows contacting
      superspecialists all over the world, asking for information on health topics. We
      report our experience with e-mail consultation with the parents of the infants
      born at our hospital.

PMID- 12236040
TI  - [Neonatal urinary ascites secondary to posterior urethral valves].
AB  - Urine collection within the perirenal spaces and subsequent urinary ascites may
      be caused either by calyceal perforation or filtration through the walls of
      urinary tract as a consequence of urinary obstruction. The obstruction to urine
      deflow is more frequently secondary to the presence of posterior urethral valves
      (PUV) in the paediatric age group. Urine collecting within the perirenal spaces
      may act as a decompressive mechanism that allows endoluminal pressure to
      decrease, being thus glomerular function and prognosis improved. The case of a
      newborn in poor clinical conditions with PUV who underwent an emergency surgical
      procedure for the onset of urinary ascites is described. On operation, no
      perforation of the upper urinary tract was found, being urinary ascites probably
      caused by filtration secondary to increased endoluminal pressure. PUV were
      coagulated by means of a Bugbee electrode and a nephrostomy set in place.
      Congenital obstruction of the urinary tract caused by PUV may lead to renal,
      ureteric and vesical damages. Surgery is necessary in order to preserve and
      improve renal function.

PMID- 12236041
TI  - Retroperitoneoscopic adrenalectomy in a residual of neuroblastoma.
AB  - The authors report a case of retroperitoneoscopic adrenalectomy in a child with
      neuroblastoma previously treated by chemotherapy. Usually the presence of
      malignant tumours is a contraindication to retroperitoneoscopic surgery. A
      restaging of the tumor was done by retroperitoneoscopy. The residual adrenal
      gland was excised by mini-invasive surgery of the retroperitoneal space. The
      histopathologic examination confirmed the presence of a residual neuroblastoma in
      the adrenal gland. This case report shows a possible of a new indication for the
      retroperitoneoscopy.

PMID- 12236042
TI  - Bilateral renal vein thrombosis as a complication of gangrenous appendicitis.
AB  - Bilateral renal vein thrombosis after an appendectomy has never been reported in
      the pediatric literature. We describe the case of a 10-year-old boy who developed
      this very unusual complication following appendectomy for gangrenous appendicitis
      with peritonitis. Color duplex Doppler is the most appropriate investigation to
      allow correct diagnosis and immediate medical treatment. Peritoneal dialysis is a
      simple and effective tool to prevent permanent damage to renal function.

PMID- 12236043
TI  - [Description of a case of primitive ciliary aplasia].

PMID- 12236044
TI  - Mode of action of gabapentin in chronic neuropathic pain syndromes. A short
      review about its cellular mechanisms in nociceptive neurotransmission.
AB  - Gabapentin (GBP, CAS 60142-96-3) has anticonvulsant and antinociceptive
      properties; the latter relate especially to chronic neuropathic pain. The mode of
      action of GBP, possibly different in epilepsy and chronic pain syndromes, is only
      poorly understood. This minireview is aimed at compiling the different mechanisms
      by which GBP may diminish the nociceptive transmission in the dorsal horn of the
      spinal cord.

PMID- 12236045
TI  - Disposition of TAK-044, a new endothelin antagonist, in rats and dogs.
AB  - The disposition of TAK-044 (cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-1
      yl)carbonyl]-L-alanyl-L- alpha-aspartyl-D-2-(2-thienyl) glycyl-L-leucyl-D
      tryptophyl] disodium, CAS 157380-72-8), a new endothelin antagonist, was studied
      in rats and dogs by using 14C-labeled drug ([14C]TAK-044). After a single
      intravenous administration of [14C]TAK-044 at 3 mg/kg to rats and dogs, the
      concentrations of TAK-044 in plasma declined biphasically; t1/2 alpha and t1/2
      beta were 0.03 and 1.10 h in rats, and 0.06 and 0.57 h in dogs, respectively.
      Plasma clearance and the volume of distribution at steady-state for TAK-044 were
      1.66 l/h/kg and 2.09 l/kg in rats, 2.37 l/h/kg and 0.50 l/kg in dogs,
      respectively. In rats, TAK-044 was distributed widely into tissues, but the 14C
      concentrations in tissues except for the liver, kidney, and intestine were lower
      than that in plasma. The in vitro protein binding amounted to 91 to 92% in rat
      plasma and 88 to 90% in dog plasma. TAK-044 was hardly distributed into the
      erythrocytes of either species. TAK-044 was hardly metabolized, the radioactivity
      in plasma and excreta being mostly unchanged compound. Elimination of the
      radioactivity from the body was almost completed within 48 h in either species.
      The dosed radioactivity was excreted mostly in the feces via the hepatobiliary
      route. The rate of excretion of TAK-044 in the bile was dose-dependently
      prolonged.

PMID- 12236046
TI  - Preformulation approaches to improve the oral bioavailability of two novel
      piperidine renin inhibitors in dog.
AB  - Different experimental formulations based on aqueous and oily systems, water
      miscible solvents, and solid dispersions were investigated for their potential to
      increase the oral bioavailability (F) of two novel piperidine renin inhibitors
      (Ro-X1: (R)-1-methoxy-3-[(3S,4R,5R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]
      phenyl]- 5-(4-methoxy-naphthalen-2-ylmethoxy)-piperidin-3-yloxy]-propan-2-ol; Ro
      X2: (R)-3-[(3S,4R,5R)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-5-(4-
      methoxy-naphthalen-2-ylmethoxy)-piperidin-3-ylmethoxy]-propane-1,2-diol) in dogs
      compared to their administration as acidic aqueous solution. The compounds were
      characterized by a low solubility at pH 7 (Ro-X1: 3 micrograms/ml, Ro-X2: 24
      micrograms/ml) and a high lipophilicity (Ro-X1: LogP = 5.7, Ro-X2: LogP = 3.7).
      For Ro-X1 oil-based vehicles resulted in an improvement in the oral
      bioavailability compared to the aqueous solution (F = 6 +/- 1.2%) with the best
      result being achieved with a solution in Capmul (F = 14.6 +/- 3.5%). By contrast,
      for Ro-X2 the highest bioavailability (F = 27.1 +/- 8.4%) was achieved using an
      aqueous solution. Computer simulations based on the physicochemical parameters of
      the compounds only predicted that the fraction of compound absorbed in man should
      be almost quantitative for Ro-X2 and only about 28% for Ro-X1. These results
      suggest that other factors such as extensive gut and/or hepatic metabolism as
      well as exclusion by intestinal transporters such as p-glycoprotein, rather than
      incomplete solubilization in the gut, are the major reasons for the limited oral
      bioavailability of both compounds.

PMID- 12236047
TI  - Effects of anti-ulcer agents on ethanol-induced gastric mucosal lesions in D
      galactosamine-induced hepatitis rats.
AB  - Patients with hepatic injury have an increased incidence of gastric ulcers and
      erosions. In this study, the effect of D-galactosamine(GalN)-induced hepatitis on
      ethanol-induced gastric mucosal lesions and the protective effect of anti-ulcer
      agents in rats were examined. Subcutaneous injection of GalN (1 g/kg) remarkably
      increased serum alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST) activities suggesting induction of hepatic injury. Gastric mucosal lesions
      induced by ethanol were significantly aggravated in GalN-induced hepatitis rats.
      Orally administered ecabet (CAS 86408-72-2; 20-200 mg/kg) dose dependently
      inhibited ethanol-induced gastric mucosal lesions in GalN-induced hepatitis rats.
      Sucralfate (CAS 54182-58-0) tended to inhibit the gastric mucosal lesions at a
      dose of 200 mg/kg but teprenone (CAS 6809-52-5), cimetidine (CAS 51481-61-9) and
      rebamipide (CAS 90098-04-7) had little effect. All anti-ulcer agents had no
      effect on the serum ALT and AST activities increased by GalN pretreatment. These
      results indicate that the gastric mucosa of GalN-induced hepatitis rats is more
      susceptible to injury induced by luminal irritants such as ethanol. Ecabet
      potently inhibited gastric mucosal lesions suggesting its clinical utility for
      the gastric mucosal damage in patients with hepatic injury.

PMID- 12236048
TI  - Study of the insulinotropic effect of the novel antihyperglycemic agent KAD-1229
      using HIT T15 cells, a hamster's insulinoma cell line.
AB  - The insulinotropic effect of (+)-monocalcium bis [(2S)-2-benzyl-3-(cis-hexahydro
      2-isoindolinyl-carbonyl)propionate] dihydrate (CAS 145375-43-5, KAD-1229) was
      assessed by comparing it with those of glibenclamide (CAS 10238-21-8),
      nateglinide (CAS 105816-04-4), and repaglinide (CAS 135062-02-1) using HIT T15
      cells, a hamster insulinoma cell line. Although their potencies were different,
      KAD-1229, glibenclamide, nateglinide, and repaglinide all concentration
      dependently and significantly induced insulin release from these cells. Further,
      each agent displaced the binding of 3H-glibenclamide to the cell membrane and
      inhibited 86Rb+ efflux from the cells. These results indicate that KAD-1229,
      glibenclamide, nateglinide, and repaglinide each exert their insulinotropic
      effect by binding to the glibenclamide binding sites (sulfonylurea receptors) on
      pancreatic beta-cells and closing K+ channels. Diazoxide, a K+ channel opener,
      and nitrendipine, a Ca2+ blocker, suppressed the insulin release induced by KAD
      1229 or glibenclamide. These results demonstrate that the insulinotropic actions
      of KAD-1229 and glibenclamide involve similar underlying pathways.

PMID- 12236049
TI  - Effects of the lipoprotein lipase activator NO-1886 as a suppressor agent of
      atherosclerosis in aorta of mild diabetic rabbits.
AB  - The synthetic compound NO-1886 ([4-(4-bromo-2-cyano-phenylcarbamoyl)-benzyl]
      phosphonic acid diethyl ester, CAS 133208-93-2) is a lipoprotein lipase activator
      which decreases plasma triglycerides and elevates high-density lipoprotein
      cholesterol (HDL-C) levels. However, the effects of NO-1886 on plasma glucose
      level and atherosclerosis in diabetes are not clear. The aim of this study was to
      ascertain whether the compound lowers plasma glucose and suppresses
      atherosclerosis in New Zealand White rabbits with high fat/high sucrose-induced
      mild diabetes. High fat/high sucrose feeding increased plasma total cholesterol,
      triglyceride and glucose levels and decreased HDL-C levels resulting in
      atherosclerosis in the aorta. Administration of NO-1886 to the rabbits resulted
      in decreased plasma total cholesterol, triglyceride and glucose levels and
      increased HDL-C levels after 20 weeks of treatment. Furthermore, NO-1886 provided
      protection against the development of atherosclerosis in the aorta. These data
      indicate that NO-1886 not only ameliorates the lipid disorder, but also lowers
      plasma glucose levels and suppresses atherosclerosis in the aorta of diabetic
      rabbits.

PMID- 12236050
TI  - [Pharmacokinetic comparison of progesterone capsules with a progesterone gel
      after vaginal administration].
AB  - The transvaginal bioavailability of 200 mg progesterone (CAS 57-83-0) from a
      vaginal capsule (Utrogest 200) compared to a vaginal gel containing 90 mg
      progesterone per dose was evaluated in 24 healthy young women using a randomised
      two-period cross-over design. Both treatments were supposed to release comparable
      amounts of progesterone. Blood samples were taken over a period of 96 h following
      single administration. Pharmacokinetic evaluation of both formulations was based
      on progesterone concentrations in serum measured by a validated RIA method. The
      relative bioavailability was determined as ratio of the AUC0-infinity and cmax
      together with the 90% confidence intervals. It could be demonstrated that one
      vaginal capsule containing 200 mg progesterone has a higher bioavailability than
      a dose of gel containing 90 mg progesterone. After administration of the capsule
      almost 50% more progesterone was bioavailable than after gel application. Both
      treatments did not vary with respect to the measured peak concentrations.
      However, tmax was clearly different. There were no relevant differences in safety
      profile between the two preparations investigated. Both were well tolerated.

PMID- 12236051
TI  - [Reduction of acute recurrence in patients with chronic recurrent hypertrophic
      sinusitis by treatment with a bacterial immunostimulant (Enterococcus faecalis
      Bacteriae of human origin].
AB  - A double-blind, placebo-controlled multicenter study in 157 patients with chronic
      recurrent sinusitis investigated the occurrence of acute relapses during
      treatment of patients with a bacterial immunostimulant (3 x 30 drops/day),
      comprised of cells and autolysate of human Enterococcus faecalis bacteria
      (Symbioflor 1, n = 78) in comparison to placebo (n = 79). The study included a
      treatment period of 6 months and a follow-up period of 8 months. Under verum the
      occurrence of relapses (50 incidents) was about half (56%) the number observed
      under placebo (90 incidents). In the Kaplan-Meier test the verum preparation
      emerged as significantly superior (p = 0.045, log rank test) compared to placebo.
      This superiority of verum was found during the treatment period with 17 vs. 33
      relapses (p = 0.019) as well as during the follow-up observation with 33 vs. 57
      relapses (p = 0.013). The time interval to the first relapse was clearly longer
      under verum (513 days) than under placebo (311 days). The relative risk for a
      relapse under the test preparation compared to placebo was 49.0% during the
      treatment and 55.8% during the follow-up period. Severity of the acute relapses
      was comparable in both groups. However, antibiotic therapy was only required in 2
      patients treated with verum compared to 6 patients in the placebo group. Both
      preparations were well tolerated and serious side effects did not occur in either
      group. No changes in laboratory tests--hematology and clinical chemistry--were
      observed. Potential immunomodifying effects of the test preparation in view of
      the significant reduction in relapses were discussed.

PMID- 12236052
TI  - Syntheses and stability studies of some Mannich bases of acetophenones and
      evaluation of their cytotoxicity against Jurkat cells.
AB  - Mannich bases, namely 1-aryl-3-dimethylamino-1-propanone hydrochlorides (Ia-f) as
      mono-Mannich bases (series I), bis(beta-aroylethyl)ethylamine hydrochlorides
      (IIa, IIb, IId, IIe) as bis-Mannich bases (series II), 3-aroyl-4-aryl-1-ethyl-4
      piperidinol hydrochlorides (series III), which are structural isomers of bis
      derivatives and some representative quaternary salts (Ig, IIIf, IIIg), were
      synthesized to investigate the effect of chemical structure and ring substituents
      on cytotoxic activity in Jurkat cells. Stability studies of some representative
      compounds have also been realised. Compounds IIb, IId, IIe, and IIIe were
      reported for the first time. Id-g, IIa, IId, IIe, IIIf,g were 1.25-6.55 times
      more potent than 5-fluorouracil (CAS 51-21-8). However, the cytotoxic activity of
      the most potent compounds. Ig and IIIf, were one fifth of that of melphalan (CAS
      148-82-3). The formation of compound IV during the stability studies of Ig, IIa,
      and IIIf suggested that they may be thiol alkylators. Bis-Mannich base IIa in
      nonsubstituted derivatives, piperidinol derivative IIIb in methyl substituted
      compounds, mono derivative Id in chloro substituted compounds were the most
      potent compounds when the cytotoxicity of the compound series which have the same
      substituents in benzene ring are compared. Replacement of the benzene with
      thiophene improved the cytotoxicity in both series I and II. Quaternization
      procedure also increased the cytotoxicity in both series I and III. Quaternary
      derivatives seem to be promising compounds for further studies to develop new
      anticancer drugs.

PMID- 12236053
TI  - Effect of fluconazole on the fertility of male rabbits.
AB  - Azole derivatives are currently available for oral treatment of systemic mycosis.
      They act by affecting the membrane permeability of sensitive cells through
      alterations of the biosynthesis of lipids, especially sterols, in the fungal
      cell. The present work was conducted to investigate the possible side effects of
      a newer azole derivative, fluconazole (CAS 86386-73-4), on fertility in sexually
      mature male rabbits and to elucidate the underlying mechanisms of this effect.
      Oral administration of fluconazole (50 mg/kg body weight in distilled water)
      daily for one month to sexually mature male rabbits induced a significant
      decrease in serum testosterone, semen volume, count and percentage of motile
      sperms. A significant increase in serum prolactin, follicle stimulating hormone
      and luteinizing hormone was observed. On the other hand, a non-significant
      alteration in percentage of abnormal sperm forms was noticed. After one month
      drug cessation, hormonal profile, sperm counts and percentage of motile sperms
      were still significantly distorted, and the whole profile reversed back towards
      normal only after the second month of drug cessation. Testicular biopsies showed
      no histopathological changes. From the above mentioned results, it can be
      concluded that fluconazole induced functional and reversible alterations in male
      fertility. Though the primary brunt of action appears to be operating on
      testicular level, however, a secondary direct interplay on higher central
      controls seems obviously contributing. Caution is advised when using azole
      derivatives in male patients, especially those on prolonged therapy.

PMID- 12236054
TI  - The biochemistry and molecular biology of lipid accumulation in oleaginous
      microorganisms.

PMID- 12236055
TI  - Transmission genetics of Microbotryum violaceum (Ustilago violacea): a case
      history.

PMID- 12236056
TI  - Molecular biology of the Koji molds.

PMID- 12236057
TI  - Noninvasive methods for the investigation of organisms at low oxygen levels.

PMID- 12236058
TI  - The development of the penicillin production process in Delft, The Netherlands,
      during World War II under Nazi occupation.

PMID- 12236059
TI  - Genomics for applied microbiology.

PMID- 12236060
TI  - Bioethanol technology: developments and perspectives.

PMID- 12236061
TI  - Progress of Aspergillus oryzae genomics.

PMID- 12236062
TI  - The transport of choline.
AB  - Choline has many physiological functions throughout the body that are dependent
      on its available local supply. However, since choline is a charged hydrophilic
      cation, transport mechanisms are required for it to cross biological membranes.
      Choline transport is required for cellular membrane construction and is the rate
      limiting step for acetylcholine production. Transport mechanisms include: (1)
      sodium-dependent high-affinity uptake mechanism in synaptosomes, (2) sodium
      independent low-affinity mechanism on cellular membranes, and (3) unique choline
      uptake mechanisms (e.g., blood-brain barrier choline transport). A comprehensive
      overview of choline transport studies is provided. This review article examines
      landmark and current choline transport studies, molecular mapping, and molecular
      identification of these carriers. Information regarding the choline-binding site
      is presented by reviewing choline structural analog (hemicholinium-3 and 15, and
      other nitrogen/methyl-hydroxyl compounds) inhibition studies. Choline transport
      in Alzheimer's disease, brain ischemic events, and aging is also discussed.
      Emphasis throughout the article is placed on targeting the choline transporter in
      disease and use of this carrier as a drug delivery vector.

PMID- 12236063
TI  - Novel choline transport characteristics in Caco-2 cells.
AB  - Choline transport is characterized by sodium-dependent high-affinity, sodium
      independent low-affinity, and sodium-independent blood-brain barrier transport
      mechanisms. Each defined mechanism has specific characteristics with regard to
      affinity for choline, transport capacity, and inhibition by hemicholinium. The
      purpose of this study is to determine the characteristics of choline transport
      across Caco-2 monolayers. METHODS: Choline transport across Caco-2 cell
      monolayers was determined in both the apical to basal direction and the opposite
      direction. Further, the determination of calcium dependence and specific
      inhibitors was made. Determination of the apparent permeability of choline was
      calculated by established methods. RESULTS: The apical to basal Caco-2
      permeability coefficient is 11.11 +/- 0.33 x 10(-6) cm/sec with 21.3% of the
      choline associating with the cells. Meanwhile the basal to apical value is
      approximately 50% less (5.55 +/- 0.14 x 10(-6) cm/sec), suggesting an active
      apical to basal transport mechanism. Choline transport in this system was
      inhibited by nifedipine (82%), verapamil (80%), EGTA (36%), and cyclosporin
      (15%). CONCLUSIONS: Choline transport across Caco-2 cells is demonstrated to be
      active and both pH- and Ca(2+)-dependent. Furthermore, choline transport across
      Caco-2 monolayers has unique characteristics when compared to traditional choline
      transport models.

PMID- 12236064
TI  - Effect of formulation variables on the floating properties of gastric floating
      drug delivery system.
AB  - PURPOSE: To evaluate the contribution of formulation variables on the floating
      properties of a gastric floating drug delivery system (GFDDS) using a continuous
      floating monitoring system and statistical experimental design. METHODS: A
      modified continuous floating monitoring system, which consisted of an electric
      balance interfacing with a PC, was designed to perform the continuous monitoring
      of floating kinetics of GFDDS. Several formulation variables, such as different
      types of hydroxypropyl methylcellulose (HPMC), varying HPMC/Carbopol ratio, and
      addition of magnesium stearate, were evaluated using Taguchi design, and the
      effects of these variables were subjected to statistical analysis. RESULTS: The
      continuous floating monitoring system developed was validated, using capsules
      with different density, and a good correlation between theoretical and
      experimental values was obtained (R2 = 0.9998), indicating the validity of the
      setup. The statistical analysis indicated that magnesium stearate had a
      significant effect on the floating property of GFDDS (p < 0.05), and addition of
      magnesium stearate could significantly improve the floating capacity of the
      GFDDS. It was found that the HPMC of higher viscosity grade generally exhibited a
      greater floating capacity, but the effect was not statistically significant. For
      polymers with the same viscosity, i.e., K4M and E4M, the degree of substitution
      of the function group did not show any significant contribution. A better
      floating behavior was achieved at higher HPMC/Carbopol ratio. Carbopol appeared
      to have a negative effect on the floating behavior of GFDDS. CONCLUSIONS: It was
      concluded that by using a validated continuous floating monitoring system, the
      effect of formulation variables on the floating property of the delivery system
      and their ranges could be identified. Incorporation of hydrophobic agents, such
      as magnesium stearate, could significantly improve the floating capacity of the
      GFDDS.

PMID- 12236065
TI  - Improving the dissolution and bioavailability of nifedipine using solid
      dispersions and solubilizers.
AB  - Nifedipine (NF) is a poorly water-soluble drug, of low and irregular
      bioavailability after oral administration. Although some reports have attempted
      to improve the dissolution of NF using solid dispersions and solubilizers, little
      literature information is available on the in vivo performance of such
      preparations. The aim of the present work was to improve the therapeutic efficacy
      of NF via incorporation into different types of carriers, and to investigate
      their in vitro dissolution and bioavailability in rabbits. Nifedipine solid
      dispersions were prepared by fusion, solvent, and freeze-drying methods with
      polyethylene glycol (PEG) 6000 and PEG monomethylether 5000 (PEG MME 5000).
      Complexation of NF with beta-cyclodextrin (beta-CyD) and solubilization by sodium
      lauryl sulfate (SLS) have also been studied. The dissolution was determined by
      the flow-through cell in order to maintain perfect sink conditions. The solid
      dispersions resulted in a significant increase in the dissolution rate as compare
      to pure drug. The highest NF dissolution rate was obtained from solid dispersions
      containing 95% PEG 6000 prepared by the solvent method. While, unexpectedly, the
      highest absorption in rabbits was obtained from 95% PEG 6000 prepared by the
      fusion method. Compared to SLS, beta-CyD gave higher in vitro and in vivo values.
      Differential scanning calorimetry (DSC) and powder x-ray diffractometry indicated
      that NF in solid dispersions is homogeneously distributed, and no drug
      crystallized out of the system. The DSC thermograms of NF-beta-CyD complex and
      NF/SLS solid mixture showed a decrease in the NF endothermic peak. The x-rays
      showed different diffraction patterns of pure NF and pure carrier, suggesting the
      formation of a new solid form.

PMID- 12236066
TI  - Tensile strength and bonding in compacts: a comparison of diametral compression
      and three-point bending for plastically deforming materials.
AB  - The tensile strength of tablets is frequently used as a measure of the bonding
      achieved during compaction. Tablets from two plastically deforming materials and
      one brittle material have been subjected to tensile strength testing using
      diametral compression and three-point bending. The plastically deforming
      materials exhibited marked inhomogeneities, with the surfaces of the tablets
      considerably more compact than the inner material. The results from the two tests
      were different, with the three-point bending test giving higher results for
      tensile strength. The rate of change of tensile strength with overall tablet
      porosity was, however, the same for the two tests. Diametral compression would
      thus appear to give a reasonable estimate of bonding despite the non-homogenous
      nature of tablets prepared from plastically deforming materials.

PMID- 12236067
TI  - A stability-indicating HPLC method to determine Celecoxib in capsule
      formulations.
AB  - A simple and accurate high-performance liquid chromatographic (HPLC) method was
      developed to determine Celecoxib in capsule formulations. The drug was
      chromatographed on a reversed-phase C-18 column. Eluents were monitored at a
      wavelength of 251 nm using a mixture (85:15) of methanol and water. Solution
      concentrations were measured on a weight basis to avoid the use of an internal
      standard. The method was statistically validated for linearity, accuracy,
      precision, and selectivity. Due to its simplicity and accuracy, we believe that
      the method will be useful for routine quality control analysis.

PMID- 12236068
TI  - In vitro release studies of flurbiprofen from different topical formulations.
AB  - The release profiles of flurbiprofen (F) from different gel and ointment
      formulations were studied in order to evaluate factors governing the release
      process. Carbopol 934P (CAB), poloxamer 407 (POL), and eudragit S100 (EUD) gel
      bases were used, while emulsion (EML) and polyethylene glycol (PEG) ointments
      were employed. The release studies were conducted using membraneless diffusion
      cells and lipophilic receptor medium, isopropyl myristate (IPM). The effects of
      gelling agent concentrations and the initial drug load on drug release were
      determined. Hydrogels were observed to give higher amounts of drug release than
      hydrophobic EUD gel and ointments, despite the lower bulk viscosity of these
      bases. Flurbiprofen release from CAB gels was 3.06-1.56-fold higher than from
      other formulations. Over a 4-hr period, the amount of F released was 492.8 and
      316.0 micrograms/cm2 from 2% CAB and 25% POL gels, while it was 213.05, 168.61,
      and 160.9 micrograms/cm2 from EML, 40% EUD, and PEG bases, respectively. The
      diffusivity of F in the gel bases was an inverse function of the polymer
      concentrations over the range of 1-3% CAB, 20-30% POL, and 35-45% EUD gels. Drug
      release was increased from the bases as the initial F concentration increased
      over the range 0.25-1.0%, while the diffusion coefficient observed an inverse
      relationship. The CAB and POL gels could be the vehicles of choice for the rapid
      release and onset of F after topical application.

PMID- 12236069
TI  - Transdermal delivery of physostigmine: effects of enhancers and pressure
      sensitive adhesives.
AB  - The purpose of this study was to investigate the effects of various pressure
      sensitive adhesives (PSA) on the percutaneous absorption of physostigmine across
      hairless mouse skin. In addition, the influences of various vehicles and
      polyvinylpyrrolidone (PVP) on the percutaneous absorption of physostigmine from
      PSA matrix across hairless mouse skin were evaluated using a flow-through
      diffusion cell system at 37 degrees C. Physostigmine showed the highest
      permeability from silicone adhesive matrix, followed by polyisobutylene (PIB),
      styrene-isoprene-styrene (SIS), acrylic, and styrene-butadiene-styrene (SBS)
      matrix. Among acrylic adhesives, the permeability of physostigmine was the
      highest from grafted acrylic adhesive. Polyvinyl pyrrolidone inhibited the
      crystallization of physostigmine in the PIB adhesive matrix and enhanced the
      permeability of physostigmine from the PIB adhesive matrix. When esters of
      sorbitol and fatty acid, polyethylene glycol (PEG) alkyl esters, and
      caprylic/capric triglycerides were tested, the more lipophilic was a surfactant,
      the higher the permeation rate within the same group of surfactants. The
      enhancement effect of PEG derivatives was lower than that of non-PEG derivatives.
      Among non-linear fatty acid derivatives, linoleate derivatives showed higher
      permeability of physostigmine than oleate derivatives. This study showed that
      several non-ionic surfactants, including PEG-20 evening primrose glyceride,
      enhanced the permeation of physostigmine across hairless mouse skin better than
      oleic acid.

PMID- 12236070
TI  - Power of experimental design studies for the validation of pharmaceutical
      processes: case study of a multilayer tablet manufacturing process.
AB  - Experimental design studies (EDS) are already widely used in the pharmaceutical
      industry for drug formulation or process optimization. Rare are the situations in
      which this methodology is applied for validation purposes. The power of this
      statistical tool, key element of a global validation strategy, is demonstrated
      for a multilayer tablet manufacturing process. Applied to the Geomatrix system
      generally composed of one compression and three granulation processes, time and
      strictness gains are non-negligible. Experimental design studies are not used in
      this work for modeling. Introduced at each important step of the process
      development, they allow for the evaluation of process ruggedness at pilot scale
      and specifications for full production. A demonstration of the complete control
      of key process parameters is given, identified throughout preliminary studies.

PMID- 12236071
TI  - Ethyl cellulose and polyethylene glycol-based sustained-release sparfloxacin
      chip: an alternative therapy for advanced periodontitis.
AB  - This study reports the development of a sustained-release system of sparfloxacin
      for use in the treatment of periodontal disease. A sustained-release sparfloxacin
      device was formulated, based on ethyl cellulose (EC) 10 cps, polyethylene glycol
      (PEG) 4000, and diethyl phthalate (DEPh). It will hereafter be called the
      sparfloxacin chip (SRS chip). The chip has dimensions of 10 mm length, 2 mm
      width, and 0.5 mm thickness. The in vitro drug release pattern and clinical
      evaluation of the formulations were studied. Reports of the short-term clinical
      study show that the use of the SRS chip may cause complete eradication of the
      pathogenic bacteria in the periodontal pockets of patients who have chronic
      generalized periodontitis. In this clinical study, the baseline and follow-up
      measurements of various clinical indices, such as oral hygiene index(es), plaque
      index, sulcular depth component of periodontal disease index, gingival crevicular
      fluid flow measurement, and dark field microscopic examinations of oral pathogens
      in plaque samples were studied. Significant improvements were observed in many
      parameters of the treatment group compared with the placebo group.

PMID- 12236072
TI  - Consideration on the formulation of benzoyl peroxide at ambient temperature:
      choice of non-polar solvent and preparation of submicron emulsion gels.
AB  - The aim of this study performed at ambient temperature was first to determine the
      solubility of benzoyl peroxide in various solvents with a large range of
      polarity. All these solvents can be used in the dermatological field. Then, using
      the most suitable solvent, a new drug vehicle submicron oil-in-water emulsion was
      formulated. Correlation between dielectric constant (epsilon) and drug solubility
      in various solvents and different binary mixtures was verified. An original
      ternary diagram with surfactant-co-surfactant/oil/water was performed at low
      temperature to determine the regions of submicron emulsions. A dramatic change in
      the magnitude of benzoyl peroxide solubility occurred above a dielectric constant
      value of about 20. The solubility of this drug can be enhanced by the replacement
      of polar solvent by a vehicle of lower dielectric constant. A stable submicron
      emulsion gel was made with cremophor EL, glycerol, caprilic-capric triglycerides,
      and water in the proportion of 20-20/35/25, respectively; 1.5% benzoyl peroxide
      was also added. This submicron emulsion vehicle consisted of oil droplets, with a
      mean diameter of approximately 100-150 nm, dispersed in a continuous water phase.
      These studies confirm the potential of benzoyl peroxide incorporation into
      submicron emulsion gel and the stability of this formulation.

PMID- 12236073
TI  - Scale-up and endpoint issues of pharmaceutical wet granulation in a V-type low
      shear granulator.
AB  - A 3(2) factorial experiment is conducted in a 57 liter low shear granulator to
      evaluate the influence of changes in binder strength and agitator speed on the
      response variables of granule size, granule morphology, granule density and
      torque input. Results are compared to previous work in a 2 liter granulator and
      scale-up issues between the two granulators are addressed.

PMID- 12236074
TI  - Physicochemical properties of CWJ-a-5, a new antitumor 3-arylisoquinoline
      derivative.
AB  - The compound CWJ-a-5 [1-(4-methylpiperazinyl)-3-phenylisoquinoline hydrochloride]
      is a novel 3-arylisoquinoline derivative which has exhibited potent antitumor
      activity. As part of an effort to develop a useful formulation for clinical
      evaluation of this compound, the aqueous stability of CWJ-a-5 as a function of
      pH, ionic strength, and temperature, as well as its various physicochemical
      properties, have been examined. The pKa value obtained by potentiometric
      titration in methanol-water mixtures was 3.61, at 25 degrees C. The aqueous
      solubility and the apparent partition coefficient of CWJ-a-5 over the pH range
      2.08-9.88 were consistent with those expected of a weak acid of similar pKa
      value. The degradation of CWJ-a-5 was found to follow apparent first-order
      kinetics. The pH-rate profiles generated at 80 degrees C were accounted for by
      acid-catalyzed degradation at low pH and base-catalyzed degradation at high pH.
      The activation energy was determined as 22.12 kcal/mol for the degradation of CWJ
      a-5 in a pH 2.92 solution with a constant ionic strength of 0.2. Increasing the
      ionic strength up to 0.9 led to a higher degradation rate constant at pH 2.92.
      However, CWJ-a-5 was very stable even in a pH 2.92 solution, and its shelf-life
      was calculated to be 2.03 years at 25 degrees C from the Arrhenius plot.

PMID- 12236075
TI  - [Evaluation of pancreatic anastomoses in the course of radical resection].
AB  - We examine the results of radical resections performed over a 10 year period at
      the 2nd Department of Surgery of the University of Debrecen Medical and Health
      Science Center Medical School of Medicine because of chronic inflammation, tumors
      of the papilla of Vater or tumors of the head of the pancreas.
      Pancreatoduodenectomy was performed in 134 patients, Whipple-type surgery in 11,
      and pylorus-preserving pancreatoduodenectomy in 123 patients. Three different
      types of reconstructive methods were used. In pylorus-preserving
      pancreatoduodenectomy, the remnant of the pancreas was anastomosed by performing
      a termino-lateral pancreatojejunostomy in 20 cases, and a pancreatogastrostomy in
      89 cases. In 14 patients, the sutures were not satisfactory because of the soft
      and glandular texture of the pancreas, so a new method was used. After removing
      the head of the pancreas, the first anastomosis was a pancreatico-jejunostomy,
      the second was a choledochojejunostomy, and the third was a duodeno-jejunostomy
      which was fixed approximately 40 centimeters from the pancreatic anastomosis. The
      most common complication was leaking pancreatogastrostomy. Four patients with
      this complication were reoperated on. The 14 patients operated on using the new
      method had no complications.

PMID- 12236076
TI  - [Effect of intravenous and intraductal glucocorticosteroids in experimental acute
      pancreatitis in dogs].
AB  - We evaluated the effect of systematically and intraductally administered
      glucocorticosteroid on experimentally induced acute pancreatitis in dogs. We
      examined histological and macroscopic changes as well as conventional laboratory
      parameters. We suggest, that low dose intraductal injection of
      glucocorticosteroid could have protective effect in acute phase of pancreatitis.

PMID- 12236077
TI  - [Video-assisted thoracoscopy (VATS) during the last ten years (1992-2001)].
AB  - We summarize and analyse the video-assisted thoracoscopies (VATS) performed in
      our department during the last ten years. In this period 296 patients underwent
      VATS for diagnosis or therapy. We describe indications, advantages and
      disadvantages, we also analyse the complications. Video-assisted thoracoscopy is
      less demanding to the patients than thoracotomy, it reduces the length and cost
      of inpatient treatment. We recommend extensive use of VATS in suitable patients.

PMID- 12236078
TI  - [Surgical aspects in the treatment of myasthenia gravis].
AB  - We treated 81 patients suffering from myasthenia with thymectomy in a 10-year
      period (1991-2000). We think, that thymectomy must be carried out in the
      treatment of myasthenia gravis, unless contraindications are present. The
      operation is not urgent and in the preoperative period patients must reach
      optimal condition with the help of standard medical treatment. The result of the
      operation is influenced by the length of time between the beginning of the
      complaints and the operation. The best results can be expected when the operation
      is performed in less than 2 years time, however an operation performed later may
      also be successful. We operated on 63% (n = 51) of the patients between 4-12
      months, on 18% (n = 15) between 13-24 months and on 18.6% (n = 15) more than 25
      months after the beginning of the complaints. Complete thymectomy was performed
      in all patients through median sternotomy. We had no operative mortality. Our
      postoperative results were evaluated with Jaretzki classification: 75% of our
      patients are in remission and asymptomatic (n = 61).

PMID- 12236079
TI  - [New indications in the treatment of advanced esophageal cancer using self
      expanding stent].
AB  - In the past four years we performed palliative reconstruction in 69 patients with
      Tygon or Polyflex self-expanding stents. The procedure was performed in 35
      patients because of mid-third oesophageal cancer, in 18 patients because of
      cancer of the cardia, in 7 patients because of mediastinal tumour and in 8
      patients because of oesophago-respiratory fistula. The procedures improved the
      swallowing greatly, the oesophago-respiratory fistulae closed. During endoscopic
      intubation of cardia tumours the risk of perforation is high, while it is lower
      in case of open operative pull-through method. Insertion of Polyflex self
      expanding stent under X-ray is safe. Improvement of the stents helps not only
      safer use, but it encourages its use in new indications, such as iatrogen benign
      perforation, corrosive oesophageal stricture, long preoperative period, when the
      swallowing for better nutrition is essential. The procedures improve the quality
      of life and improve survival time because of the restored swallowing, closed
      oesophago-respiratory fistula with the prevention of aspiration.

PMID- 12236080
TI  - [Surgical treatment for primary and secondary tumors of the liver].
AB  - We performed liver resection for focal liver disease in 266 patients between
      January 1, 1992 and December 31, 2001 at the University of Debrecen Medical and
      Health Science Center, Medical School of Medicine, 2nd Department of Surgery in
      Debrecen, Hungary. The indication was primary liver cancer in 35 cases, liver
      metastasis in 97 cases. The primary tumour and its liver metastases were removed
      synchronously in 28 patients (29.9%). Comparing the results of different
      operating methods we found the need of transfusion significantly less in
      "anterior" liver resections. Regarding operating time, complications and survival
      time there were no significant differences between the different operations. One
      patient died in the perioperative period because of cardiac failure and one
      because of DIC (1.5%). There were 4 complications which needed reoperation in the
      early postoperative period. Eighty of the patients were treated with systemic
      adjuvant chemotherapy (Mayo protocol), with added chemoembolisation in another 26
      patients. This has not increased life expectancy significantly. Thirty-two
      patients are still alive, their average survival time is 21.2 (5 to 59) months.
      The average survival time of the 78 patients' who died is 16.5 (3 to 58) months.
      Twenty-two patients were lost out of our follow-up.

PMID- 12236082
TI  - [The role of D2 lymphadenectomy in the surgical treatment of gastric carcinoma].
AB  - The authors examine 145 patients with gastric carcinoma who underwent curative
      resection with additional D2 lymphadenectomy at the 2nd Surgical Department of
      DUMHSC between January 1, 1996 and December 31, 2000. Subtotal resection was
      performed in 103 patients, and total, gastrectomy was performed in 42 patients.
      Postoperative mortality was 5.5% and disease-related complications occurred in
      17.9%. The three-year survival was 49.7%, while in patients with "early" (maximum
      infiltration to the level of the submucosa) gastric carcinoma 3-year survival
      rate of was 86.3%. The results correlate with the data in the literature, so the
      use of D2 lymphadenectomy in the surgical treatment of gastric carcinoma is
      strongly advised.

PMID- 12236081
TI  - [Reconstruction of cervical esophageal anastomosis using median sternotomy].
AB  - We performed cervical oesophageal anastomosis in 153 patients in 10 years. In 11
      patients reconstruction or delayed anastomosis was performed through median
      sternotomy because cervical approach was not suitable. Reoperations were the
      following: 7 oesophageal stenosis which couldn't be dilated, 2 necrosis of the
      transplanted organ and 2 because of delayed anastomosis. 8 patients had
      oesophageal tumors and 3 erosive fluid reflux. During median sternotomy the
      transplanted organ was injured twice. In 9 patients after reconstruction
      dysphagia disappeared, in one pharyngo-ileostomy stenosis was noticed and one of
      the patients died because of ARDS after a leak.

PMID- 12236083
TI  - [Therapeutic strategy in acute necrotizing pancreatitis].
AB  - We describe our therapeutic principles in connection with the treatment of 43
      patients (30 male and 13 female) with acute necrotizing pancreatitis. The
      etiology of the disease was alcohol in 72.1%, gallstones in 23.3%, trauma,
      hyperlipidemia, ERCP and unknown in 4.7%. In all patients, the necrosis was
      proved by CT and histological examination. The patients were treated in intensive
      care unit. It involved prophylactic antibiotics (Imipenem) and early nasojejunal
      feeding. In each case, we endeavoured to delay surgery, which was a wide
      necrosectomy extending to the retroperitoneum. In 13 patients (30.2%) CT-guided
      percutaneous drainage was performed because of extensive peripancreatic fluid.
      Ten such patients were operated on at a later time. In 81.4% (35 patients) an
      average of 1.8 operations were performed. The first indications were acute
      abdomen, septic necrosis and multi-organ failure (MOF) unreactive to conservative
      therapy. Five patients (11.6%) were cured with conservative treatment and 3
      patients (7%) were cured by treatment which included percutaneous drainage.
      Twenty-seven reoperations were performed in 12 patients because of sepsis,
      suspected peritonitis, abscess, bleeding and gastro-intestinal perforation. The
      average hospital stay was 44.5 days (3-120 days) long, and mortality was 16.2%.
      In our opinion in addition to intensive therapy, prophylactic antibiotics, early
      nasojejunal feeding and late, delayed surgery are important in the treatment of
      acute necrotizing pancreatitis. Percutaneous peripancreatic drainage is a useful
      way to delay operation. These therapeutic possibilities improve the survival rate
      of patients with pancreatic necrosis.

PMID- 12236084
TI  - [Surgical treatment of pleural metastases in breast cancer].
AB  - Pleural metastases of breast cancer is a severe progression of the disease and
      the treatment is difficult. Distant metastases are mainly treated by chemo-,
      radio- or hormone therapy, but in recent years surgical intervention is
      increasingly important. Between the 1st of January 1992 and 31st of December 2001
      in the 2nd Department of Surgery University of Debrecen Medical and Health
      Science Center Medical School of Medicine 43 patients with breast cancer were
      operated on because of pleural metastases. In these patients biopsy and
      pleurodesis with talcum insufflation were performed. The surgical treatment was
      followed by chemotherapy. Pleurodesis was successful at 76.7 percent. The 6, 12
      and 24 months survival was 58.1, 39.5 and 16.3 percent. Based on literature data
      and own experience we conclude that surgical intervention with adjuvant therapy
      extends life expectancy for patients with pleural metastases. Pleurodesis can
      prevent or delay hydrothorax, it improves vital functions and the quality of life
      for patients with pleural metastases.

PMID- 12236085
TI  - [Early results after minimal lobectomy for benign nodular goiter].
AB  - Following traditional operations (enucleation and subtotal resection) for benign
      nodular goiters recurrences may develop. Reoperations for this condition can
      cause complications, such as hypoparathyroidism and damage of the recurrent
      laryngeal nerve. That is why total thyroidectomy is recommended by many
      specialists in benign thyroid disease. We performed lobectomy on one side, and,
      if necessary, partial resection on the other side. Lobectomy was performed on one
      side in 31 cases, with partial resections on the other side in 73 patients. We
      tried to identify the parathyroid glands and both recurrent laryngeal nerves.
      Postoperative complications were evaluated. Temporary dysfunction of the
      recurrent laryngeal nerve was detected in 2.3%, permanent damage in 1.1%.
      Temporary hypocalcaemia developed in 16.4%, permanent hypocalcemia in 1.9%. Two
      reoperations were necessary for bleeding. Because of the low postoperative
      complication rate we recommend this method as an alternative to thyroidectomy for
      benign nodular goiters. We know that our favourable results can be compared with
      traditional subtotal resection and thyroidectomy when long term results of
      thyroid function and data about nodular recurrences will be collected.

PMID- 12236086
TI  - [Jejunal feeding in necrotizing pancreatitis or after esophagectomy].
AB  - Has early jejunal glutamine-rich diet any advantage in the treatment of patients
      suffering from acute pancreatitis and after oesophagectomy? Eleven patients
      suffering from necrotizing pancreatitis and 23 patients operated on radically for
      esophageal cancer were fed intra jejunally with glutamine-rich Stresson Multi
      Fibre diet. Eight patients with necrotising pancreatitis and 13 oesophagectomy
      patients were fed with glutamine-poor Nutrition Multi Fibre. Nutritional status,
      serum proteins, acute phase proteins, immune-globulins, complement components
      (C3, C4), the ratio of subsets of peripheral lymphocytes were analysed on the
      1st, 2nd, 4th and 10th days. Serum protein parameters were measured by laser
      nephelometry. CD cell surface antigen expression was measured with flow
      cytofluorometry, activity of phagocytes with whole blood chemiluminescences.
      Laboratory parameters showed an improvement during the 10-day-treatment in both
      diet types, but significant improvement could be measured only in patients with
      necrotizing pancreatitis and fed with Stresson Multi Fibre: IgG (p < 0.05), serum
      protein (p < 0.02), prealbumin (p < 0.05), retinol binding protein (p < 0.03).
      The different diets did not cause difference in the laboratory results of the
      oesophagectomy patients. Early immune-enhancing diet improved serum proteins,
      acute phase proteins and immunoglobulins significantly in necrotizing
      pancreatitis. The length of hospital stay also decreased.

PMID- 12236087
TI  - [Significance of bad habits in orthodontics].
AB  - The author is concerned with the etiological role of bad habits in the
      development. Disturbances caused by pacifier habits, finger sucking, various
      forms of swallowing habits and their therapeutical possibilities are discussed.
      The role of mouth breathing, nail biting, bruxism and self-mutilation in
      development of anomalies and their therapy are also mentioned. The attention is
      called to the fact that dentists have responsibility and task to diagnose as
      early as can be the oral bad habits and that the adequate therapy in time in co
      operation with other specialists helping the child get out of bad habits,
      preventing the development of severe anomaly.

PMID- 12236089
TI  - [Hepatitis C virus infection and its dental implications].
AB  - In the last two decades dentists and other dental workers have been called
      attention to the risk of infection with blood-borne pathogens by a few reports.
      Before Hepatitis B vaccine became available in 1982, dentists and oral surgeons
      were reported to have a higher prevalence of Hepatitis B Virus (HBV) than other
      health-care workers and the general population. The first cases of AIDS were
      recognised in 1981, and in 1988 dentists infected with Human Immunodeficiency
      Virus was already registered without any other potential risk factor except his
      occupation. Hepatitis C Virus (HCV), a positive stranded RNA virus was isolated
      for the first time from a chronically infected chimpanzee by a human VIII factor
      concentrate. Now HCV is regarded to be the cause of most cases of non-A-non-B
      hepatitis. Although the risk of HCV infection among health-care workers is lower
      than it was in the case of HBV infection, there is some evidence of occupational
      transmission of HCV. The lack of effective vaccine, the proportion of chronic
      infections, and the limited success of therapy emphasises the importance of the
      problem for the dentists in practice. In this report the authors surveyed the
      epidemiology, transmission, and nature of HCV infection, and suggested some
      possible connection between the virus and certain oral diseases. The authors
      expounded some general aspects of management of HCV-infected patients in the
      dental practice and underlined the importance of preventing occupational
      transmission.

PMID- 12236088
TI  - [Experience with the clinical use of beta-tri-calcium phosphate (Cerasorb) as a
      bone replacement graft material in human periodontal osseous defects].
AB  - Various bone replacement graft materials have been used in attempting to restore
      periodontal bone structure lost as a result of periodontal inflammation. The pure
      beta-tricalcium phosphate has been successfully used in oral surgery for
      replacing lost bone but the periodontal data available are very limited. The
      major objective of the present clinical trial is to evaluate the regenerative
      reparative potential of beta-tricalcium phosphate (CERASORB) in the treatment of
      two-three-wall vertical periodontal bony defect. 21 patients with advanced
      intrabony defects were selected for this study. Parameters used for assessment:
      Bleeding on probing, Clinical Probing Depths (CPD), Clinical Attachment Loss
      (CAL), Clinical Gingival Recession (CGR) and Radiological evaluation on
      standardized periapical radiographs. Following local anesthesia, intracervicular
      incisions is placed and a full thickness mucoperiosteal flap is raised
      vestibularly and lingually. The granulation tissue was completely removed from
      the defects and the roots were thoroughly scaled and planed using hand and
      ultrasonic instruments. Osseous recontouring was not performed. Following defect
      debridement, the CERASORB bone-grafting material was carefully applied and gently
      condensed in the bone crater then the flaps were repositioned in a coronal
      position and closed with vertical or horizontal mattress sutures. Six months
      after surgery CPD, CAL and CGR parameters were also measured and compared to
      baseline data. Bone defects treated with beta-TCP bone grafting materials showed
      a great variation in healing tendency. The best radiological results (bone fill)
      were obtained in three wall defects. Even using the most thorough suturing
      technique substantial part of the bone grafting material was lost during the
      first post-surgical week. If no sequestration occurred substantial bone fill and
      clinical attachment gain occurred especially in the three wall defects one year
      after grafting. The use of biological barrier membranes are recommended.

PMID- 12236091
TI  - [Kinetic study of the liquid uptake of retraction cords].
AB  - The soaking time ensured for the liquid uptake of retraction cords is a crucial
      factor in the successful gingival retraction procedure. The aim of the present
      investigations was to determine the optimal soaking time for three cords of
      different thickness. The capability of liquid uptake of the cords was measured by
      a gravimetric method using four different sulcus retraction solutions. In
      addition to the time of soaking, the saturation of the cords with the solutions
      largely depended on the wetting properties and the pore structure of the cords as
      well. Our results indicate that 20 minutes soaking time is necessary for
      saturation before using in the clinical application of the cords. This conclusion
      applies for conditions when air bubbles are manually removed before soaking.

PMID- 12236090
TI  - [Mathematical description of the three-dimensional axis of the root canal of
      human teeth].
AB  - The objective of the present study was to describe root canal axes of natural
      human teeth mathematically. Two views (clinical and proximal) radiographs were
      taken from extracted human teeth. Geometry defines the 90-degree turn-around
      image pairs as Monge images. These Monge images of the root canals were
      positioned using photogrammetric methods. Each well-ordered axis pair of a given
      root canal was put into a common coordinate system resulting in three-dimensional
      polynomial function of the actual root canal. Testing differences between
      determined and repeatedly determined axes of ten samples by statistical analysis
      did not show any significant differences. Evaluation of data gained on a large
      number of samples may also yield a new type of classification.

PMID- 12236092
TI  - [Prosthetic rehabilitation of cleft palate patients with fixed partial dentures].
AB  - Treatment of cleft palate patients demands a well coordinated work of medical and
      dental specialists. In spite of the surgical and orthodontic therapy a prosthetic
      rehabilitation is often necessary because of missing teeth, maxillary hypoplasia,
      malocclusion and palatal defects. The prosthetic phase begins immediately after
      the orthodontic treatment. In this way the fixed partial denture replaces the
      retention appliance and stabilizes the achieved status. The aim of the prosthetic
      treatment is to improve the function of the masticatory apparatus, speech and
      aesthetic appearance of the patient. An important task of the prostheses is to
      support and lift up the upper lip and the base of the nose. There are several
      factors, which make the treatment difficult, like underdeveloped and collapsed
      maxillary arch, retrognath position of the maxilla, missing alveolar ridge,
      defects of the bone and mucosa, scars and stiffness of the upper lip. The
      maintenance of the oral hygiene with the fixed restorations is often difficult
      because of the stiffness of the upper lip, therefore the design of the pontic is
      very important especially in the cases, when the missing processus alveolaris has
      to be replaced in order to improve the harmony of the face.

PMID- 12236093
TI  - Calcium-binding proteins in the human developing brain.
AB  - Recent studies have demonstrated that antibodies against the calcium-binding
      proteins (CaBPs) parvalbumin (PV), calbindin (CB), and calretinin (CR) are
      appropriate tools for demonstrating transient features and developmental changes
      of human fetal brain organization as well as for detecting specific alterations
      in pathologically altered specimens. CB and CR are abundantly expressed in
      various nerve cell types of the subplate in the second half of gestation. The
      subplate being an outstandingly wide zone subjacent to the cortical plate, it is
      a "waiting compartment" for various cortical afferents that reside here prior to
      entering the cortical plate. The cortical plate (future layers II-VI of the
      cerebral cortex) contains only CR-ir neurons until the 6th gestational month. In
      the 7th and 8th month, cortical CB- and PV-ir interneurons are observed in deeper
      portions of the cortical plate. Cajal-Retzius cells of layer I are CR
      immunolabeled from the 4th month onwards. Fetal hydrocephalus causes severe
      alterations of CB- and PV-ir neurons in the subplate and the cortical plate:
      shrinkage of ir neurons, loss of process labeling and in most severe cases,
      entire loss of immunolabeling. Such alterations, which cannot be detected in
      Nissl-stained sections, indicate distinct impairment of neuronal function. The
      ganglionic eminence being a prominent part of the telencephalic proliferative
      zone persists nearly throughout the entire fetal period. Between 16 and 24 weeks
      of gestation, CR-ir cells are found in the center and, in a higher number, in the
      periphery, i.e., the mantle zone, of the ganglionic eminence. The mantle zone
      also exhibits CB-ir cells. These observations support experimental data showing
      that CR-ir precursor cells leave the ganglionic eminence to migrate towards the
      cerebral cortex. The CR- and CB-ir neurons of the mantle zone most probably
      represent an intermediate target for outgrowing axons. This notion is supported
      by the observation that SNAP (synaptosomal associated protein) 25-ir fibers
      coming from the intermediate zone terminate upon CR-ir cells in the mantle zone.
      Within the amygdaloid complex, immature, migrating CR- or CB-ir neurons are
      observed in the 5th and 6th gestational month. In the 8th and 9th month, anti-CR
      and anti-CB mark different subsets of interneurons as well as a small proportion
      of pyramidal projection neurons. The different subsets of interneurons are likely
      to be functionally different with regard to their connectivities. Considering
      studies in the literature, it is obvious that CR is transiently expressed in
      pyramidal cells. Moreover, diffuse (neuropil) CB and CR immunolabeling, which is
      found in different intensities in the various amygdaloid subdivisions, displays
      distinct redistribution during development, an observation indicating
      reorganization of afferent inputs. The sequential arrival of various afferent
      fiber systems in the two compartments of the striatum (patch and matrix
      compartment) is reflected by changing patterns of diffuse CB immunolabeling:
      During the second half of gestation, the patches are labeled and postnatally a
      changeover to matrix labeling is seen. The thalamic reticular complex reveals
      prominent transient features seen in PV and CR immunopreparations. Four
      subdivisions become obvious: the main portion, the perireticular nucleus, the
      medial subnucleus, and the pregeniculate nucleus. The PV- and CR-ir perireticular
      nucleus, not visible in the mature brain, is a distinct fetal entity located
      within the internal capsule. The main portion of the reticular complex is much
      more prominent in the fetus than in the adult and displays transitory CR
      expression. The most probable developmental role of the reticular complex is to
      provide guiding cues for outgrowing axons from or into the dorsal thalamus. The
      basal nucleus of Meynert and the hypothalamic tuberomamillary nucleus both
      provide extrathalamic projections to the cerebral cortex. The sequential
      differentiation of the two nuclei can be demonstrated using anti-CB and anti-PV.
      The basal nucleus strongly expresses CB and appears to be mature distinctly
      earlier than the PV-ir tuberomamillary nucleus. Antisera against CaBPs clearly
      demonstrate that the magnocellular part of the red nucleus located in the
      mesencephalic tegmentum is outstanding in the fetal and perinatal brain and
      inconspicuous in the adult. In particular, CB is the most abundant CaBP in this
      portion of the red nucleus. The dominance of the magnocellular part over the
      parvocellular part may be a substrate for a specific transitory pattern of motor
      behavior. On the whole, CaBPs mark the transient architectonic organization of
      the brain, which is involved in the establishment of transitory neuronal
      circuitries. The latter are essential for the formation of mature projections.
      Detailed data on the normal organization of the transient structures are required
      for the evaluation of alterations occurring in the fetal and perinatal brain. The
      transient structures are sites of predilection for alteration caused by hypoxia
      ischemia, hemorrhage, or hydrocephalus.

PMID- 12236094
TI  - [Microtubule dynamics in epithelial cells].
AB  - Microtubules (MTs) are necessary components of all eukaryotic cells. They fulfill
      various functions being involved in cell division, ciliar and flagellar beating,
      cell shape maintaining, organelle distribution in the cell, organization of other
      cytoskeletal elements. Dynamic features of MTs have been commonly studied in
      vitro or on undiffirentiated cultured cells by means of molecular and
      ultrastructural methods. It is generally accepted that the phenomenon of dynamic
      instability is the major mechanism of MT turnover in the cell. MTs radiate from
      the centrosome and take part in the distribution of cell organelles. In addition,
      epithelial, nerve, and skeletal muscle cells contain non-centrosomal MTs. A few
      hypothesis of their origin have been so far put forward. According to the capture
      release hypothesis, MTs are first nucleated on the a centrosome, then release to
      be driven in various parts of the cell by molecular motors. Some alternative
      mechanisms of non-centrosomal MT formation are also proposed in literature. For
      example, the nucleation sites were reported not only in centrosomes but also in
      other parts of cells, such as the apical membranes of epithelial cells, the
      nuclear membrane of muscle cells, pigment granule aggregates of melanophores. On
      studying frog urinary bladder and large intestine epithelial cells the authors
      observed in these cells numerous non-centrosomal MTs. This makes epithelial
      cells, good models for analysing structural and dynamic features of non
      centrosomal MTs in differentiated cells. For the urinary bladder the pool of
      specific granules may serve as MT organizing centers. Non-cenrosomal MTs of these
      cells have big diameters (35-38 nm) and form bundles oriented in the apical-basal
      axis of the cell. In addition, non-centrosomal MTs of these cells may participate
      in the transport of specific granules and giant vacuoles that appear under
      stimulated water flows through the cell.

PMID- 12236095
TI  - [Electron microscope study of haemolymph cells of Metrioptera roeselii
      (Orthoptera, Tettigoniidae)].
AB  - On the basis of patterns of haemocyte ultrastructure and functions at preimago
      and imago stages of Metrioptera roeselii, secretory cells of granulocyte type
      were recognized in the haemolymph. The development of granulocytes was traced
      starting from their formation up to cell death and destruction. The haemocytes
      develop as "dark" and "light" cells, differing in their functional activity,
      although their ultrastructure is similar. In the cytoplasm of granulocytes,
      granules of both mitochondrial and nuclear origin were detected. Simultaneously
      two processes occur in the cells--the accumulation and discharge of granules.

PMID- 12236096
TI  - [Reorganization of the tubulin and actin cytoskeleton under acclimation and
      abscisic acid treatment of Triticum aestivum L. plants].
AB  - Only scanty and contradictory data are available concerning effects of low
      temperatures and ABA on the structural organization of microtubules (MTs) and
      microfilaments (MFs), and no information exists on the interaction of these
      parameters at cold acclimation of plants. Therefore, in cold acclimate and ABA
      treated winter wheat plants, a comparative study was made of the state
      (localization, orientation, structure) and stability of actin and tubulin
      cytoskeleton in root cells taken from different zones, using indirect
      immunofluorescent microscope. The plant cold acclimation caused MT aggregation,
      the rise of MT and MF fluorescence, and the increase of their stability (a
      decrease of oryzalin effect) mainly in the root differentiation zone, that may
      testify to the strengthening of contacts between MTs and MFs. Like the cold
      acclimation, ABA induced the formation of MT bunches only in meristem and
      elongation zone cells. However in the zone of differentiation, the hormone
      stimulated the increase of tubulin structure stability, well correlating with a
      decrease in MT content, aggregation degree, and immunofluorescence, and, in
      addition with a complete depolymerization of MFs. Low temperatures removed the
      hormone effect on the structural organization of tubulin and actin cytoskeleton
      in the zone of differentiation. It is suggested that MT destruction, the decrease
      of instable MT populations, and the increase of stable MT populations may slow
      down growth processes in ABA-treated plants, similarly as in seedlings being on
      the initial stages of cold acclimation. By the end of this process, the induction
      of plant growth is determined evidently by the increase in the number of
      instable, highly labile MT populations, and in the status of MF polymerization.

PMID- 12236097
TI  - [Store-operated cationic channels in human myeloid leukaemia K562 cells].
AB  - Using the whole-cell patch clamp technique, single channels operated by
      intracellular Ca(2+)-store depletion were first revealed in human myeloid
      leukaemia cells K562. A single store-operated channel could be detected in
      divalent-free extracellular solutions with Na+ as a permeant ion, and
      intracellular solutions with strong Ca(2+)-helating agent with some delay after
      whole-cell formation. Addition of inositol-1,4,5-triphosphate to the pipette
      solution resulted in a significant decrease of this latency. These channels had a
      conductance of 29 pS, and were inhibited by low concentration of external Ca2+.
      Our results enable us to assume that the revealed channels are calcium release
      activated calcium channels, operated by Ca2+ depletion of endoplasmic reticulum.

PMID- 12236098
TI  - [Involvement of protein kinase C in the regulation of Ca2+ exit from
      intracellular stores of prolactin stimulated pig oocytes].
AB  - Involvement of protein kinase C in the regulation of Ca2+ exit from intracellular
      stores of pig oocytes activated by prolactin was investigated, using the
      fluorescent dye chlortetracycline. In the presence of extracellular calcium, the
      inhibitor of protein kinase C Ro 31-8220 increased calcium exit from
      intracellular stores in pig oocytes after prolactin treatment. In calcium-free
      medium, Ro 31-8220 exerted effect on calcium release from intracellular stores.
      In calcium-free medium, prolactin did not stimulate calcium release from
      intracellular stores of oocytes in the presence of thimerosal, while in the
      presence of protein kinase C inhibitor, prolactin increased Ca2+ content from
      intracellular stores in such oocytes. These data suggest a direct involvement of
      protein kinase C in the processes of regulation of Ca2+ exit from intracellular
      stores of pig oocytes stimulated by prolactin.

PMID- 12236099
TI  - [Dark recovery of diploid yeast cells after simultaneous exposure to UV
      irradiation and hyperthermia].
AB  - Quantitative regularities of dark recovery of wild-type diploid yeast cells of
      Saccharomyces cerevisiae simultaneously treated with UV-light (254 nm) and high
      temperatures (53-56 degrees C) were studied. Under this combined action, the
      constant of recovery, which defines the probability of elimination of the UV
      radiation induced damage per unit of time, did not depend on the temperature of
      irradiation. It was shown that both the irreversible component of cell damage and
      the number of cells that died without division gradually increased as the
      temperature of exposure increased. It is concluded, on this basis, that the
      mechanism of synergistic interaction of UV-radiation and hyperthermia is related
      not to the inhibition of dark recovery itself, but to the increase in the shape
      of irreversibly damaged cells incapable of recovering from the induced damage.

PMID- 12236100
TI  - [Internal symmetry of the mirror type in the primary structure of ribozymes].
AB  - Internal symmetry of the mirror type has been first found in molecules of RNA
      referred to as ribozymes. For identification and investigation of the internal
      symmetry in RNA primary structure, two methods were developed, dot matrix and
      scanning, respectively. The methods are based on a comparison of normal and
      reversible nucleotide sequences. The objects of our study was ribozymes from
      introns of Tetrahymena thermophila and hepatitis delta virus, and also a group of
      related ribozymes, possessing both cleavage and ligation activities. The centers
      of internal symmetry are mainly localized in the catalytic sites and other
      important regions of ribozyme molecules. A positive correlation was found between
      the conservativity and symmetry of the primary structure of ribozymes. However,
      this correlation was not so clear in comparison with the correlation in the case
      of proteins. As reported earlier (Shpakov, 1995, 2001), the internal symmetry was
      discovered in protein and DNA molecules. The obtained data enable us to consider
      the internal symmetry as a common characteristics of nucleotide and amino acid
      sequences of the biopolymers.

PMID- 12236101
TI  - [A cross drug resistance of mammalian cells with a high efficiency of "DNA
      clearing"].
AB  - The process of active dissociation of noncovalently bound agents from DNA or "DNA
      clearing" in the living cells was described elsewhere. The vital fluorescent
      bisbenzimidazole dye Hoechst 33342 (4342), which binds tightly but not covalently
      to DNA in the minor groove, was used for studying interactions of agents
      noncovalently binding with DNA. The "DNA clearing" is an energy-dependent
      process, which is suppressed by topoisomerase-II inhibitors and DNA breaks. It
      has been shown that the rodent fibroblast cell line AA8HoeR-7 is selected for
      resistance to H342, and characterized by an enhanced dissociation of the
      bisbenzimidazole dye-DNA complex. This cell line obtained cross-resistance to
      other DNA damaging drugs: mitomycin C, etoposide and ethidium bromide. That
      proves that AA8HoeR-7 is cell line with a new mechanism of multidrug resistance.

PMID- 12236102
TI  - [Intracellular localization of XCAP-E and pEg7 condensins in normal mitosis and
      after the treatment inducing artificial changes in structural organization of
      mitotic chromosomes].
AB  - Function of condensin subunits XCAP-E and pEg7 (XCAP-D2) in the formation and
      maintaining of special organization of mitotic chromosomes has been studied in
      Xenopus laevis cells (XL-2). The experimental conditions involved blocking
      chromosomes being in the condensed state in cells treated by cytostatics, or
      during their reversible artificial decondensation. The latter was induced by
      incubation of living cells in hypotonic medium. In extensively mollen
      chromosomes, XCAP-E and pEg7, remained associated with axial regions of
      chromosomes. In contrast, upon adaptation of cells to hypotonic conditions and
      recondensation of chromosomes to nearly initial state, both proteins dissociated
      from chromosomes into the cytoplasm. In K-mitotic cells, after a 3-6 h treatment
      with nocodazole or taxol, considerable dissociation of XCAP-E and pEg7 from
      chromosomes was observed without significant changes in overall level of
      chromosome compactization. Taken together the data suggested that condensins play
      no important role in maintaining mitotic chromosomes being in condensed state.
      Rather, it seems probable that mitotic function of condensins may be associated
      either with the formation of the higher order chromosome structure, and/or
      segregation of sister chromatids, the processes being tightly linked with
      chromosome compactization. This paper is in memory of Professor Katherine Le
      Guellec of Rennes-1 University, who left us in June 2001. Professor Le Guellec
      initiated this work in Rennes and offered all the possible help that this work be
      continued in Moscow University. Let the memory of Katherine, a great scientist
      and sympathetic friend, live for ever in ours hearts.

PMID- 12236103
TI  - [Stereospecific DNA anomalies in the human chromosome 21].
AB  - Using our own original computer program, we analysed more than 10 millions b.p.
      of the complete nucleotide sequence in the human chromosome 21. A graphic
      catalogue of largest stereospecific anomalies of this sequence is presented.
      Clusters of different stereospecific anomalies, showing presumably areas of
      cooperative binding of different regulatory and structural proteins to DNA have
      been revealed. Most of the large stereospecific anomalies are situated in
      introns, being often accompanied by regions devoid of some specific
      dinucleotides.

PMID- 12236104
TI  - [Stability in association of the peripheral material with mitotic chromosomes].
AB  - The localization of nucleolar proteins (fibrillarin and B-23), and of the protein
      of interphase nuclear matrix (NMP-65) was studied in the perichromosomal material
      (CM) after of short hypotonic treatment (15% solution of Henks medium) on
      cultured pig embryonic kidney cells, followed by restoration of isotonic
      conditions. It is shown that during hypotonic shock the mitotic chromosomes
      demonstrate reversible swelling, but their periphery is bounded with a rim of
      PCM, containing antibodies to fibrillarin and NMP-65, but not to B-23. After
      returning the cells to the initial isotonic medium, all the three proteins can be
      detected again on the periphery of chromosomes. It suggests the existence of
      different stability in the association of free proteins with chromosome bodies.
      Besides, B-23 and fibrillarin could be visualized in residual nucleoli after a
      complete extraction of histones and DNA from nuclei.

PMID- 12236105
TI  - [The structure of the surface apparatus in sarcocysts of Sarcosporidia in the
      persistence process].
AB  - The structure of the sarcocyst surface apparatus (SSA) was investigated for two
      sarcosporidian species: Sarcocystis muris (non-pathogenic) and S. fusiformis
      (pathogenic). The surface membrane, being the main SSA subsystem, makes numerous
      vesicle-like protrusions with different ultrastructural patterns. This made it
      possible to distinguish between four and three types of these protrusions in S.
      fusiformis and S. muris, respectively. Vesicles of similar structure, pinched off
      from the fully formed protrusions, were classified, correspondingly, in the same
      four and three different types. A presumable functional role of both protrusions
      and membrane-coated vesicles in pathogenicity of different sarcosporidian species
      is proposed. The vesicles pinched off from corresponding protrusions may be
      involved in transporting certain substance complexes from the sarcocyst to the
      harbouring host cell. In addition, another way of substance transporting was
      observed, when the cystic substances, not surrounded with any membrane coating,
      are thrown from open protrusions directly into the immediate cytoplasm of the
      host cell.

PMID- 12236106
TI  - Efficacy and tolerance of selected antiseptic substances in respect of
      suitability for use on the eye.

PMID- 12236107
TI  - Antisepsis versus antimicrobial chemotherapy and indications for eye antisepsis.

PMID- 12236108
TI  - Importance and epidemiology of infectious eye diseases.

PMID- 12236109
TI  - Incidence of endophthalmitis in ophthalmic surgery.

PMID- 12236110
TI  - Methicillin-resistant Staphylococcus aureus in ophthalmology, occurrence,
      sanitation measures and hygienic precautions.

PMID- 12236111
TI  - Microbial colonization of the eye as target for antiseptics.

PMID- 12236112
TI  - Nosocomial virus infections of the eye.

PMID- 12236113
TI  - Prophylactic indications for eye antiseptics. Pre-, intra- and postoperative
      antisepsis in eye surgery.

PMID- 12236114
TI  - Prophylactic indications for eye antiseptics. Prophylaxis against ophthalmia
      neonatorum.

PMID- 12236115
TI  - Prophylactic indications for eye antiseptics. Measures for prevention of
      infection via corneal transplants.

PMID- 12236116
TI  - Therapeutic indications for local anti-infectives. Bacterial infections of the
      eye.

PMID- 12236117
TI  - Therapeutic indications for local anti-infectives. Recommendations for isolation
      and antiseptic sanitation of patients with MRSA colonization or infection.

PMID- 12236118
TI  - Therapeutic indications for local anti-infectives. Topical antimycotic drugs.

PMID- 12236119
TI  - Requirements concerning antiseptics for periorbital, orbital and intraorbital
      application. Antimicrobial efficiency.

PMID- 12236120
TI  - Therapeutic indications for local anti-infectives. Viral ocular infections:
      topical treatment and prevention.

PMID- 12236121
TI  - Therapeutic indications for local anti-infectives. Anti-infectives against amebic
      keratitis.

PMID- 12236122
TI  - Preventive measurements to avoid the transmission of relevant pathogens after
      occurrence of infection.

PMID- 12236123
TI  - Hand hygiene.

PMID- 12236124
TI  - Requirements concerning antiseptics for periorbital, orbital and intraorbital
      application. Local tolerance.

PMID- 12236125
TI  - Contact lens hygiene.

PMID- 12236126
TI  - Antimicrobial efficacy of contact lens care products and critical comment on
      ISO/FDIS 14729.

PMID- 12236127
TI  - Sampling and transport of specimens for microbial diagnosis of ocular infections.

PMID- 12236128
TI  - Requirements concerning antiseptics for periorbital, orbital and intraorbital
      application. Systemic tolerance of antiseptics used in ophthalmology.

PMID- 12236129
TI  - Requirements concerning antiseptics for periorbital, orbital and intraorbital
      application. Pharmacokinetics of ophthalmic drugs.

PMID- 12236130
TI  - Requirements concerning antiseptics for periorbital, orbital and intraorbital
      application. Formulation requirements for the ophthalmic use of antiseptics.

PMID- 12236131
TI  - The eye and conjunctiva as target of entry for infectious agents: prevention by
      protection and by antiseptic prophylaxis.

PMID- 12236132
TI  - Proceedings of the International Workshop on Multi-Analyte Biosensing Devices. 13
      14 April 2000, Athens, Greece.

PMID- 12236133
TI  - Proceedings of the International Society of Non-Invasive Cardiology, 18th
      European Congress. September 20-22, 2001. Krakow, Poland.

PMID- 12236134
TI  - [XXXVI Congress of the French College of Vascular Pathology. Paris, 12-15 March
      2002. Abstracts].

PMID- 12236135
TI  - Proceedings of the XV National Congress of the Polyspecialty Society of Pediatric
      Surgery. 23-35 May 2002.

PMID- 12236137
TI  - [A new hysteroscope and its practical use in gynecology].

PMID- 12236141
TI  - Abstracts of papers presented at the Joint Meeting of the SIB Group of Marine and
      Environmental Biochemistry, Interdepartmental Research Center of Marine Sciences
      of the Bologna University and Marine Research Center of Cesenatico. June 1, 2001.

PMID- 12236142
TI  - [Presentation banquet for the "Archivos Espanoles de Urologia" prizes. XXIV
      issuing of the Perez Castro Prizes].

PMID- 12236144
TI  - Bibliography of toxinology.

PMID- 12236143
TI  - Markets for organs: myths and misconceptions.

PMID- 12236145
TI  - Testicular implants and patient satisfaction: a questionnaire-based study of men
      after orchidectomy for testicular cancer.

PMID- 12236146
TI  - Establishment of a testicular carcinoma cell line producing alpha-fetoprotein.

PMID- 12236147
TI  - Testicular function following chemotherapy.

PMID- 12236148
TI  - MAGE-A4, a germ cell specific marker, is expressed differentially in testicular
      tumors.

PMID- 12236149
TI  - Chromosome abnormalities of eighty-one pediatric germ cell tumors: sex-, age-,
      site,- and histopathology-related differences--a Children's Cancer Group Study.

PMID- 12236150
TI  - Wet gangrene in hemodialysis patients with calciphylaxisis is associated with a
      poor prognosis.

PMID- 12236151
TI  - An inherited p53 mutation that contributes in a tissue-specific manner to
      pediatric adrenal cortical carcinoma.

PMID- 12236152
TI  - Long term outcome in adult males with classic congenital adrenal hyperplasia.

PMID- 12236153
TI  - Long-term (10-15 years) follow-up after Burch colposuspension for urinary stress
      incontinence.

PMID- 12236154
TI  - Objective and subjective cure rates after tension-free vaginal tape for treatment
      of urinary incontinence.

PMID- 12236155
TI  - Polypropylene sling for the treatment of stress urinary incontinence.

PMID- 12236157
TI  - Subjective and objective incontinence 5 to 10 years after Burch colposuspension.

PMID- 12236156
TI  - A systematic review of tension-free urethropexy for stress urinary incontinence:
      intravaginal slingplasty and the tension-free vaginal tape procedures.

PMID- 12236158
TI  - Pancreas after kidney transplants.

PMID- 12236159
TI  - Are wound complications after a kidney transplant more common with modern
      immunosuppression?

PMID- 12236161
TI  - Kidney transplantation in children weighing less than 15 kg: donor selection and
      technical considerations.

PMID- 12236160
TI  - Nonsurgical treatment of acute iatrogenic renal artery injuries occurring after
      renal artery angioplasty and stenting.

PMID- 12236162
TI  - Capillary C4d deposition in kidney allografts: a specific marker of alloantibody
      dependent graft injury.

PMID- 12236163
TI  - Is contrast as bad as we think? Renal function after angiographic embolization of
      injured patients.

PMID- 12236165
TI  - Proceedings of the Eighth International Symposium on Equine Reproduction, Fort
      Collins, USA, July 2002.

PMID- 12236164
TI  - Lower genitourinary injury and pelvic fractures in pediatric patients.

PMID- 12236166
TI  - Treating prisoners with HIV/AIDS: the importance of early identification,
      effective treatment, and community follow-up.

PMID- 12236167
TI  - Acquired rifampin resistance in AIDS-related TB.

PMID- 12236168
TI  - K channels as molecular targets for the treatment of erectile dysfunction.

PMID- 12236169
TI  - Nitric oxide regulation of penile erection: biology and therapeutic implications.

PMID- 12236170
TI  - The molecular basis of erectile physiology: from bench to bedside.

PMID- 12236172
TI  - Employees on continued medication: identification and discussion of problems with
      employees, continuing on medication, as noted on the occupational health scene.
      1978.

PMID- 12236171
TI  - Inhibition of tonic contraction--a novel way to approach erectile dysfunction.

PMID- 12236173
TI  - Surgeons: extend HIV testing to patients.

PMID- 12236174
TI  - Politics. Congressmen want account of U.S. funds spent at AIDS conference.

PMID- 12236175
TI  - CDC-funded HIV/AIDS programs under White House review.

PMID- 12236176
TI  - Wrongful termination. Dismissal of floral worker's termination case reversed on
      appeal.

PMID- 12236177
TI  - State department declares AIDS a foreign policy imperative.

PMID- 12236179
TI  - Model predicts antiretrovirals could halt HIV in 50 years.

PMID- 12236178
TI  - U.S. to withhold $34 million in funds for U.N. AIDS, population control.

PMID- 12236180
TI  - Historical diseases might help predict AIDS progression.

PMID- 12236181
TI  - Fees awarded to AIDS patient mistakenly stripped of insurance.

PMID- 12236182
TI  - Negligence. Vacate dismissal denied for woman wrongly told she had HIV.

PMID- 12236183
TI  - Retaliation case against blood bank dismissed by court.

PMID- 12236185
TI  - Current and emerging management strategies in chronic ear disease. Proceedings of
      a symposium. St. Helena, California, USA. January 18-20, 2002.

PMID- 12236184
TI  - Dismissal granted to Red Cross in African transfusion case.

PMID- 12236186
TI  - Bibliography. Current world literature. Pediatric and heritable disorders.

PMID- 12236187
TI  - Bibliography. Current world literature. Osteoarthritis.

PMID- 12236188
TI  - Association between birth weight and adult disorders in twins: validity of self
      reported birth weight.

PMID- 12236189
TI  - Birthweight in dizygotic twins.

PMID- 12236192
TI  - [Solicitude].

PMID- 12236194
TI  - AIDS stigma forms an insidious barrier to prevention/care. HIV experts describe
      problem in India.
AB  - When the HIV/AIDS epidemic's toll including 40 million people living with the
      disease and 3 million having died in 2001, the world's health and service
      organizations are increasingly calling for better access to care and treatment
      for people living in the developing nations that share the brunt of the
      epidemic's devastation. ONe of the most insidious barriers to reaching those who
      are at risk for HIV is the disease's stigma, particularly in sub-Saharan Africa
      and India, which together account for more than 32 million of those who are
      infected.

PMID- 12236193
TI  - HIV/AIDS epidemic wreaks havoc on youths worldwide. 800,000 infants infected last
      year.
AB  - News from the 14th International AIDS Conference, held in July in Barcelona,
      Spain, highlighted the problem of the AIDS epidemic among young people, who are
      the most represented among new infections. Moreover, young women of childbearing
      age have become infected at alarming rates in many developing nations, and as
      they grow ill and die, they leave a giant gap in the societal framework.

PMID- 12236195
TI  - New Delhi group shares 2 case studies of HIV discrimination.
AB  - According to directors with the Health Institute for Mother and Child in New
      Dehli, India, HIV stigma and discrimination can have severe social and health
      consequences for those who are infected. Here are two examples.

PMID- 12236196
TI  - Unwitting trust of sexual partners result in infection.

PMID- 12236197
TI  - Global walks teach teens to fight HIV/AIDS epidemic. Organization supported
      entirely by volunteers.
AB  - AIDS Alert asked John Chittick, EdD, executive director of TeenAIDS-PeerCorps
      Inc., a nonprofit organization in Boston, to discuss the global walks he founded
      and an abstract he presented at the 14th International AIDS Conference in
      Barcelona, Spain. According to the abstract, global walks began in 1999 with
      Chittick spreading the word by foot about HIV/AIDS in 40 countries to teen
      volunteers, who, in turn, were expected to educate their peers about HIV
      prevention. Within two years, the global walk had reached 75,000 youth, who
      taught HIV prevention through such techniques as Stop Action Theater, street
      outreach 'AIDS Attacks,' and 'AIDS Comics,' which were drawn by teens. Also,
      there is a Teen Advice Column available in multiple languages on the Internet.

PMID- 12236198
TI  - U.S. prevention strategies focus on involving youths. Strategies include theater,
      youth planning groups.
AB  - With an estimated 20,000 new HIV infections in the United States each year among
      youth younger than 25, there have been many efforts in recent years to find
      effective prevention programs targeting that population. Among the intervention
      strategies highlighted at the 14th International AIDS Conference in Barcelona,
      Spain, were two that have been developed by AIDS Alliance for Children, Youth &
      Families of Washington, DC.

PMID- 12236199
TI  - Monitoring indicates safe-sex relapse in Boston.
AB  - The trend of men who have sex with men (MSM) resorting to increasingly unsafe
      sexual practices is apparent in the developed world, as studies continue to
      highlight increases in the prevalence of sexually transmitted diseases. Studies
      presented at the 14th International AIDS Conference in Barcelona, Spain, showed
      increasing trends of STDs among MSM in New England's largest MSM clinical care
      site and at Paris STD clinics. Fenway Community Health in Providence, RI has
      charted STD trends among gay men and lesbians in New England for three decades.
      The clinic's records showed that the lowest prevalence rate in STDs had occurred
      in the late 1980s and early 1990s, after AIDS deaths had become a strong
      motivating factor in safe sex practices.

PMID- 12236200
TI  - Internet paging system help improve adherence. Counseling is combined with
      reminders.
AB  - HIV patients in Boston who began a study with very low medication adherence made
      some improvements after several months of being prompted by an Internet-based
      paging system, but their adherence still was far from the 90% goal of HIV
      medication treatment programs, according to a study presented at the 14th
      International AIDS Conference in Barcelona, Spain.

PMID- 12236201
TI  - Proposed diagnostic criteria and nosology of acute transverse myelitis.
AB  - Acute transverse myelitis (ATM) is a focal inflammatory disorder of the spinal
      cord, resulting in motor, sensory, and autonomic dysfunction. A set of uniform
      diagnostic criteria and nosology for ATM is proposed to avoid the confusion that
      inevitably results when investigators use differing criteria. This will ensure a
      common language of classification, reduce diagnostic confusion, and lay the
      groundwork necessary for multicenter clinical trials. In addition, a framework is
      suggested for evaluation of individuals presenting with signs and symptoms of
      ATM. Best treatment often depends on a timely and accurate diagnosis. Because
      acute transverse myelopathies are relatively rare, delayed and incomplete work
      ups often occur. Rapid and precise diagnosis will ensure not only that
      compressive lesions are detected and treated but also that idiopathic ATM is
      distinguished from ATM secondary to a known underlying disease. Identification of
      etiologies may suggest medical treatment, whereas no clearly established medical
      treatment currently exists for idiopathic ATM. Establishment of a diagnostic
      algorithm will likely lead to improved care, although it is recognized that the
      entire evaluation may not be performed for each patient.

PMID- 12236202
TI  - [The many faces of contact in caring].
AB  - This paper emerged from a group experience about a theme related to human care:
      the contact. The experience is described, unveiling feelings and memories
      perceived while constructing the activity, building a concept of contact, here
      seen as one of the fundaments of human care. Human care was studied on an
      anthropological approach, lived in a group technique. Our meanings of contact
      were expressed with the words: senses, sensibility, representation, confidence,
      relationship. Each significance was worked and detailed since our concept of
      contact arose from the interrelation of them. Some theoretical reflection about
      the theme was done and constructs of this kind of care were elaborated, since it
      is considered one of the fundaments of human care.

PMID- 12236203
TI  - [The meaning of care in the perspective of nurse aides students].
AB  - This is a descriptive exploratory study. It aims to identify the meaning of care
      in Nursing on the perspective o eighteen Nurse aides students. To collect the
      data, it was asked to the students to write down an answer to the following
      question: "What is the meaning of care to me?" The data was separated in groups
      that pointed to two categories and their elements: the expressive care and the
      professional care. Expressive care presented itself as: affection, giving, being
      present, protection, concerning, being available, understanding, respecting,
      comforting, being responsible, solidarity, providing security, having intention,
      sharing/exchanging. Professional care showed to be: assist/care, technical
      competence, professional knowledge and to like what is done.

PMID- 12236204
TI  - Barcelona conference: new online report.

PMID- 12236205
TI  - ACTG 384 at Barcelona: the bottom line.

PMID- 12236206
TI  - Nandrolone: generic now in stock.

PMID- 12236207
TI  - Barcelona comments.

PMID- 12236208
TI  - Report on the XIV International AIDS Conference.

PMID- 12236209
TI  - Building user participation to reshape services for people affected by motor
      neurone disease.

PMID- 12236210
TI  - CDC shifts prevention focus to HIV carriers.

PMID- 12236211
TI  - Africa activists threaten legal action if HIV drug withdrawn.

PMID- 12236212
TI  - Tennessee AIDS clinic provides success story.

PMID- 12236213
TI  - Global Health Council promotes common agenda to stop AIDS.

PMID- 12236215
TI  - Motion to dismiss denied in fraudulent viatical insurance case.

PMID- 12236214
TI  - Seaman can't recover from employer for HIV maintenance, cure.

PMID- 12236216
TI  - Life insurance in short supply for people with HIV/AIDS.

PMID- 12236217
TI  - UNAIDS officials say AIDS battle must be taken to world political stage.

PMID- 12236218
TI  - Brazil shares blueprint of successful battle against HIV/AIDS.

PMID- 12236219
TI  - Companies pressured to cover employees' AIDS drugs.

PMID- 12236220
TI  - Conviction upheld for couple promoting unsafe HIV/AIDS therapy.

PMID- 12236221
TI  - Transfusion. Blood cleansing deemed safe, but more donors required.

PMID- 12236222
TI  - Ethicists say yes to transplants for HIV-positive patients.

PMID- 12236223
TI  - Transplants. AIDS warning prompts recall of body parts.

PMID- 12236224
TI  - [National guideline for diabetes mellitus type 2, abridged version. May 2002.
      Federal Chamber of Physicians].

PMID- 12236225
TI  - Abstracts of the Swiss Society of Allergology and Immunology annual meeting.
      Lugano, March 14-16, 2002.

PMID- 12236226
TI  - American Society of Nephrology 2002 Renal Week. Philadelphia, Pennsylvania, USA.
      October 30-November 4, 2002. Abstracts.

PMID- 12236227
TI  - Abstracts of the 24th Annual Meeting of the American Society for Bone and Mineral
      Research. San Antonio, Texas, USA. September 20-24, 2002.

PMID- 12236228
TI  - A user's guide to the human genome.

PMID- 12236229
TI  - [Oxidative stress and genetic polymorphism in COPD].
AB  - Chronic obstructive pulmonary disease (COPD) is characterised by progressive
      diminution of pulmonary function with minimal reversibility. The initially organ
      related symptoms gradually involve secondary organs and end-stage COPD can be
      considered a systemic disease. The most important cause of COPD is tobacco
      smoking. In recent years there has been increasing focus on the
      pathophysiological events leading to COPD, and oxidative stress has been
      suggested as one of the major pathophysiological factors. Clinical studies
      indicate a causal association between tobacco smoking, oxidative stress,
      increased inflammatory response, and destruction of lung parenchyma. This article
      reviews the clinical literature on oxidative stress as a pre-inflammatory state,
      leading to COPD in susceptible smokers.

PMID- 12236230
TI  - European Society for Magnetic Resonance in Medicine and Biology 19th Annual
      Meeting. Cannes, France, August 22-25, 2002. Abstracts.

PMID- 12236231
TI  - Abstracts of the 10th European Conference on Health Records--Managing Health
      Information in the 21st Century. Trinity College Dublin, 25-29 August 2002.

PMID- 12236232
TI  - Abstracts from the 2002 Annual Conference of the Canadian Pain Society. May 23
      25, 2002, Winnipeg, Manitoba, Canada.

PMID- 12236233
TI  - The American Academy for Cerebral Palsy and Developmental Medicine 2002 Annual
      Meeting. Abstracts.

PMID- 12236234
TI  - Abstracts of the Swiss Society for Infectious Diseases annual meeting. Fribourg,
      June 20-22, 2002.

PMID- 12236235
TI  - EuroSpine 2002. Abstracts of the 4th Annual Meeting of the Spine Society of
      Europe. September 11-14, 2002. Nantes, France.

PMID- 12236237
TI  - [VI Congress of the International Association of Morphologists. Abstracts].

PMID- 12236236
TI  - Supreme Court focuses on more disability-related issues than ever before.

PMID- 12236238
TI  - Abstracts of the 27th Sir Peter Freyer Memorial Lecture 2002 in association with
      the Irish Society of Surgical Oncology. 6-7 September 2002, Galway, Ireland.

PMID- 12236239
TI  - Ophthalmological Society of the West Indies 13th Annual Congress. July 10-13,
      2002. St Croix, US Virgin Islands. Abstracts.

PMID- 12236240
TI  - Abstracts of the 4th International Congress of Pathophysiology. Budapest,
      Hungary, June 29-July 5, 2002.

PMID- 12236241
TI  - REGPEP 2002. Abstracts of the 14th International Symposium on Regulatory
      Peptides. Boston, Massachusetts, USA. August 31-September 3, 2002.

PMID- 12236242
TI  - Selecting an accurate point-of-care testing system: clinical and technical issues
      and implications in neonatal blood glucose monitoring.
AB  - ISSUES AND PURPOSE: Rapid identification and treatment of glucose abnormalities
      is crucial in the prevention of potentially devastating neurological injury in
      neonates. Choice of a point-of-care glucose testing system must consider
      accuracy, clinical advantages, and data management capabilities. CONCLUSIONS: The
      benefits and limitations of point-of-care testing must be weighed against the
      time delay of central laboratory testing. PRACTICE IMPLICATIONS: Considerations
      in selecting a point-of-care blood glucose monitoring system include accuracy,
      precision, versatility, and the potential for cross infection and blood loss.
      When a system is selected, studies must be done to identify potential sources of
      error and confirm the utility and accuracy of the system in the identified
      population.

PMID- 12236243
TI  - Promoting normalization in families with preschool children with type 1 diabetes.
AB  - ISSUES AND PURPOSE: The family environment is the most important influence on
      child adaptation to type 1 diabetes. A plan of care assists parental adaptation
      in families with a preschool child with type 1 diabetes. CONCLUSIONS: The family
      environment is affected by the family's progress toward normalcy. Normalization
      can be facilitated by nursing interventions that promote parental mutuality in
      management and the development of a parental support system. PRACTICE
      IMPLICATIONS: Nurses can provide education about Type 1 diabetes and its
      management in preschool children to fathers, other family members, and family
      friends to encourage their involvement in caregiving. Parental mutuality in
      management and an adequate parental instrumental support system facilitates
      normalization and affects the family environment, thus promoting child
      adaptation.

PMID- 12236244
TI  - Volunteering--a community partnership.

PMID- 12236245
TI  - Meeting the standard of genetic nursing care.

PMID- 12236246
TI  - Helping children cope with separation during war.

PMID- 12236247
TI  - Let's get a grip.

PMID- 12236248
TI  - How can we help foster children?

PMID- 12236249
TI  - Mothers' experiences raising young children with type 1 diabetes.
AB  - ISSUES AND PURPOSE: To examine the day-to-day experiences of mothers raising
      children 4 years of age and younger with type 1 diabetes. DESIGN AND METHODS: The
      descriptive design compared mothers of children with (n = 25) and without
      diabetes (n = 25). Mother-child observations were completed for children with
      diabetes. RESULTS: Mothers of children with diabetes are very skilled in reading
      their children's behavioral cues. Mothers' concerns included the fear of
      hypoglycemia and seizure activity, access to daycare centers, and babysitting
      services capable of caring for their children's condition. These responses
      significantly differed from the control group mothers. PRACTICE IMPLICATIONS:
      Nurses can affirm that hypoglycemia-related fears are normal and help mothers
      identify community resources that might ease the burden of care required,
      especially during the early postdiagnosis period.

PMID- 12236250
TI  - Caloric nystagmus after plugging of the horizontal semicircular canal in pigeons.
AB  - The mechanism of caloric nystagmus has been attributed to endolymphatic
      thermoconvection flow of the horizontal semicircular canal in the inner ear. It
      has recently become difficult, however, to explain caloric nystagmus provoked in
      the space experiment by employing the convection theory only because the
      convection phenomenon does not exist under the conditions of microgravity (0G).
      Although several hypotheses concerning the mechanism of caloric nystagmus have
      been proposed which exclude the convection theory, opinions remain divided among
      investigators as to the mechanism governing caloric nystagmus under conditions of
      normal gravity (1G) and 0G. In this study, we confirmed that the convection
      theory represents the mechanism of caloric nystagmus under 1G using pigeons
      (Columba livia). The direction of caloric nystagmus was dependent upon the head
      position and the stimulus site of calorization in the semicircular canal. But
      after the plugging of the semicircular canal, however, caloric nystagmus
      disappeared. These results strongly support the theory that the primary
      mechanisms of caloric nystagmus under 1G are controlled by the convection
      phenomenon of the endolymph in the semicircular canal.

PMID- 12236251
TI  - Report outlines evidence supporting 79 patient safety practices.

PMID- 12236252
TI  - Choice of care delivery site influences pneumonia management.

PMID- 12236253
TI  - Three-part stroke assessment enables early, accurate prediction of recovery.

PMID- 12236254
TI  - Diabetes management program reduces spending.

PMID- 12236255
TI  - Where to go for practical advice.

PMID- 12236256
TI  - The right to die with dignity with the assistance of a physician: an Anglo,
      American and Australian international perspective.

PMID- 12236257
TI  - Corporate hydrology: profit by growth or by acquisition?

PMID- 12236258
TI  - The hydro-malaprop and the ground water table.

PMID- 12236259
TI  - Permeability changes in layered sediments: impact of particle release.
AB  - One of the mechanisms of sudden particle release from grain surfaces in natural
      porous media is a decrease in salt concentration of the permeating fluid to below
      the critical salt concentration. Particle release can cause a change in hydraulic
      conductivity of the matrix, either by washing out the fines and thus increasing
      the pore sizes or by the plugging of pore constrictions. The phenomenon of
      permeability changes as a result of particle detachment was investigated in a
      series of column experiments. Coarse and fine sediments from the Hanford
      Formation in southeast Washington were tested. Columns were subject to a pulse of
      highly saline solution (NaNO3) followed by a fresh water shock causing particle
      release. Outflow rates and changes in hydraulic head as well as electric
      conductivity and pH were monitored over time. No permeability decrease occurred
      within the coarse matrix alone. However, when a thin layer of fine sediment was
      embedded within the coarse material (mimicking field conditions at the Hanford
      site), permeability irreversibly decreased to 10% to 20% of the initial value.
      Evidence suggests that most of this permeability decrease was a result of
      particles detached within the fine layer and its subsequent clogging. An
      additional observation was a sudden increase in pH in the outflow solution,
      generated in situ during the fresh water shock. Because layered systems are
      common in natural settings, our results suggest that alteration between sodium
      solution and fresh water can lead to particle release and subsequently reduce the
      overall permeability of the matrix.

PMID- 12236260
TI  - Determination of confined phreatic aquifer anisotropy.
AB  - The determination of anisotropy in a phreatic aquifer by means of a pumping test
      can be carried out, under given conditions, with common analysis methods. This
      paper develops and applies an amended method based on a technique proposed by
      Boulton (1970). This new method enables a quick, simple determination of vertical
      hydraulic conductivity, given drawdown data from a pumping well and at least one
      observation well, that is applicable to confined phreatic aquifers.

PMID- 12236261
TI  - Dynamic optimal ground water remediation including fixed and operation costs.
AB  - In time-varying ground water remediation, the lack of an optimal control
      algorithm to simultaneously consider fixed costs and time-varying operating costs
      makes it nearly impossible to obtain an optimal solution. This study presents a
      novel algorithm that integrates a genetic algorithm (GA) and constrained
      differential dynamic programming (CDDP) to solve this time-varying ground water
      remediation problem. A GA can easily incorporate the fixed costs associated with
      the installation of wells. However, using a GA to solve for time-varying policies
      would dramatically increase the computational resources required. Therefore, the
      CDDP is used to handle the subproblems associated with time-varying operating
      costs. A hypothetical case study that incorporates fixed and time-varying
      operating costs is presented to demonstrate the effectiveness of the proposed
      algorithm. Simulation results indicate that the fixed costs can significantly
      influence the number and locations of wells, and a notable total cost savings can
      be realized by applying the novel algorithm herein.

PMID- 12236262
TI  - Asymmetric dipole-flow test in a fractured carbonate aquifer.
AB  - In this study, a new method-the asymmetric dipole-flow test-is proposed and
      tested for characterization of conductive properties and structure of fractured
      aquifers. Analytical solutions were developed and then used for interpretation of
      a modification of the dipole-flow test with a single packer at the Bissen Quarry
      test site (Wisconsin, USA). The asymmetric dipole-flow tests were conducted by
      packing a well at various elevations, and fluids were pumped from the upper
      section (chamber) of the well to the lower section (chamber). The head was then
      monitored at 11 observation points and in both sections of the well, and the
      conductivities of the well segments were determined. The tests at seven packer
      elevations in the well were rapid (less than one hour to reach steady state). The
      asymmetric dipole-flow test demonstrates the potential to quantify
      heterogeneities of a fractured aquifer and delineate the applicability of the
      continuum and discrete approaches for conceptualization of ground water flow.

PMID- 12236263
TI  - Is the forward problem of ground water hydrology always well posed?
AB  - Complex aquifer systems are often modeled with quasi-three-dimensional models,
      which consider two-dimensional horizontal flow in the aquifers and one
      dimensional vertical flow through aquitards. When the aquifer system consists of
      a phreatic aquifer and one or more semiconfined aquifers connected by aquitards,
      the discrete model consists of a nonlinear system of algebraic equations, because
      the transmissivity of the phreatic aquifer depends on the phreatic head. If the
      water extraction is very high, the phreatic aquifer can be depleted and the
      equations of the model must be modified accordingly. There are not simple and
      general criteria to state if the phreatic aquifer is depleted before solving the
      system of equations. Therefore, the iterative procedures (e.g., relaxation
      methods), used to find the solution to the forward problem, must handle these
      particular conditions and can suffer several problems of convergence. These
      problems can be caused by the choice of the initial head values or of the
      relaxation coefficient of the iterative algorithms; however, they can also be
      caused by the nonexistence or nonuniqueness of the solution to the system of
      nonlinear equations. The study of existence and uniqueness of the general problem
      is very difficult and, therefore, we consider a simplified problem, for which the
      discrete model can be handled analytically. The results of the numerical
      experiments show that the solution to the forward problem can be nonunique. Only
      for some cases it is possible to invoke physical arguments to eliminate tentative
      solutions.

PMID- 12236264
TI  - Measurement of 3-D hydraulic conductivity in aquifer cores at in situ effective
      stresses.
AB  - An innovative and nondestructive method to measure the hydraulic conductivity of
      drill core samples in horizontal and vertical directions within a triaxial cell
      has been developed. This has been applied to characterizing anisotropy and
      heterogeneity of a confined consolidated limestone aquifer. Most of the cores
      tested were isotropic, but hydraulic conductivity varied considerably and the
      core samples with lowest values were also the most anisotropic. Hydraulic
      conductivity decreased with increasing effective stress due to closure of
      microfractures caused by sampling for all core samples. This demonstrates the
      importance of replicating in situ effective stresses when measuring hydraulic
      conductivity of cores of deep aquifers in the laboratory.

PMID- 12236265
TI  - Spatial and temporal variability of ground water recharge in central Australia: a
      tracer approach.
AB  - Two environmental tracer methods are applied to the Ti-Tree Basin in central
      Australia to shed light on the importance of recharge from floodouts of ephemeral
      rivers in this arid environment. Ground water carbon-14 concentrations from
      boreholes are used to estimate the average recharge rate over the interval
      between where the ground water sample first entered the saturated zone and the
      bore. Environmental chloride concentrations in ground water samples provide
      estimates of the recharge rate at the exact point in the landscape where the
      sample entered the saturated zone. The results of the two tracer approaches
      indicate that recharge rates around one of the rivers and an extensive floodplain
      are generally higher than rates of diffuse recharge that occurs in areas of lower
      topographic relief. Ground water 2H/1H and 18O/16O compositions are all depleted
      in the heavier isotopes (delta2H = -67 per thousand to -50 per thousand; delta18O
      = -9.2 per thousand to -5.7%o) compared with the long-term, amount-weighted mean
      isotopic composition of rainfall in the area (delta2H = -33.8 per thousand;
      delta18O = -6.3 per thousand). This indicates that recharge throughout the basin
      occurs only after intense rainfall events of at least 150 to 200 mm/month.
      Finally, a recharge map is developed to highlight the spatial extent of the two
      recharge mechanisms. Floodout recharge to the freshest ground water (TDS <1,000
      mg/L) is approximately 1.9 mm/year compared with a mean recharge rate of
      approximately 0.2 mm/year to the remainder of the basin. These findings have
      important implications for management of the ground water resource.

PMID- 12236266
TI  - Influence of the amount of available K data on uncertainty about contaminant
      transport prediction.
AB  - The effect of increasing the amount of hydraulic conductivity (K) data on the
      level of uncertainty about contaminant concentration predictions was examined.
      Contaminant concentrations were predicted using Monte Carlo numerical simulations
      with progressively more K information, and were compared to reference data
      obtained from a physical experiment. Increasing the amount of K data used in
      generating the aquifer's K field improved the measure of confidence in the
      predicted contaminant concentration. The normalized concentration interval with
      95% confidence decreased from 1.29 to 0.75 when the amount of K data increased
      from 20 to 71. However, the trade-off is the increase in the costs of aquifer
      investigation. Conducting Monte Carlo numerical simulations may help design an
      optimal aquifer investigation scheme, so that it can provide enough input data to
      predict concentrations with the desired level of confidence and at the same time
      avoid the excessive costs of aquifer investigation.

PMID- 12236267
TI  - Analysis of a vertical dipole tracer test in highly fractured rock.
AB  - The results of a vertical dipole tracer experiment performed in highly fractured
      rocks of the Clare Valley, South Australia, are presented. The injection and
      withdrawal piezometers were both screened over 3 m and were separated by 6 m
      (midpoint to midpoint). Due to the long screen length, several fracture sets were
      intersected, some of which do not connect the two piezometers. Dissolved helium
      and bromide were injected into the dipole flow field for 75 minutes, followed by
      an additional 510 minutes of flushing. The breakthrough of helium was retarded
      relative to bromide, as was expected due to the greater aqueous diffusion
      coefficient of helium. Also, only -25% of the total mass injected of both tracers
      was recovered. Modeling of the tracer transport was accomplished using an
      analytical one-dimensional flow and transport model for flow through a fracture
      with diffusion into the matrix. The assumptions made include: streamlines
      connecting the injection and withdrawal point can be modeled as a dipole of equal
      strength, flow along each streamline is one dimensional, and there is a constant
      Peclet number for each streamline. In contrast to many other field tracer studies
      performed in fractured rock, the actual travel length between piezometers was not
      known. Modeling was accomplished by fitting the characteristics of the tracer
      breakthrough curves (BTCs), such as arrival times of the peak concentration and
      the center of mass. The important steps were to determine the fracture aperture
      (240 microm) based on the parameters that influence the rate of matrix diffusion
      (this controls the arrival time of the peak concentration); estimating the travel
      distance (11 m) by fitting the time of arrival of the centers of mass of the
      tracers; and estimating fracture dispersivity (0.5 m) by fitting the times that
      the inflection points occurred on the front and back limbs of the BTCs. This
      method works even though there was dilution in the withdrawal well, the amount of
      which can be estimated by determining the value that the modeled concentrations
      need to be reduced to fit the data (approximately 50%). The use of two tracers
      with different diffusion coefficients was not necessary, but it provides
      important checks in the modeling process because the apparent retardation between
      the two tracers is evidence of matrix diffusion and the BTCs of both tracers need
      to be accurately modeled by the best fit parameters.

PMID- 12236268
TI  - Interpretation of spring recession curves.
AB  - Recession curves contain information on storage properties and different types of
      media such as porous, fractured, cracked lithologies and karst. Recession curve
      analysis provides a function that quantitatively describes the temporal discharge
      decay and expresses the drained volume between specific time limits (Hall 1968).
      This analysis also allows estimating the hydrological significance of the
      discharge function parameters and the hydrological properties of the aquifer. In
      this study, we analyze data from perennial springs in the Judean Mountains and
      from others in the Galilee Mountains, northern Israel. All the springs drain
      perched carbonate aquifers. Eight of the studied springs discharge from a karst
      dolomite sequence, whereas one flows out from a fractured, slumped block of
      chalk. We show that all the recession curves can be well fitted by a function
      that consists of two exponential terms with exponential coefficients alpha1 and
      alpha2. These coefficients are approximately constant for each spring, reflecting
      the hydraulic conductivity of different media through which the ground water
      flows to the spring. The highest coefficient represents the fast flow, probably
      through cracks, or quickflow, whereas the lower one reflects the slow flow
      through the porous medium, or baseflow. The comparison of recession curves from
      different springs and different years leads to the conclusion that the main
      factors that affect the recession curve exponential coefficients are the aquifer
      lithology and the geometry of the water conduits therein. In normal years of
      rainy winter and dry summer, alpha1 is constant in time. However, when the dry
      period is longer than usual because of a dry winter, alpha1 slightly decreases
      with time.

PMID- 12236269
TI  - Origin of shallow ground water in an alluvial aquifer as determined by isotopic
      and chemical procedures.
AB  - In this study, we identify the origin of shallow ground water that supports
      regionally unique plant and wildlife habitats in a riparian and reservoir-fringe
      system using isotopic and chemical procedures. This study was conducted where
      Little Stony Creek flows into East Park Reservoir on the east front of the Coast
      Range, northern California. Little Stony Creek water, Hyphus Creek water,
      Franciscan Complex regional ground water, Great Valley Group regional ground
      water, and local shallow ground water were collected during wet and dry seasons
      and were analyzed for deuterium, oxygen-18, temperature, pH, redox potential,
      conductivity, and major cation and anion concentrations. Turnover in the local
      flow system is rapid indicating that local shallow ground water is dependent on
      recent recharge. Local shallow ground water is recharged primarily by Little
      Stony Creek water and Franciscan Complex ground water. In the wet season, Little
      Stony Creek is the more prominent source of local shallow ground water, and the
      ratio of Little Stony Creek water to Franciscan Complex ground water decreases
      with distance from the channel. In the dry season, Franciscan Complex ground
      water is the more prominent source of local shallow ground water, and the ratio
      of Little Stony Creek water to Franciscan Complex ground water decreases with
      distance down the valley. Franciscan Complex ground water discharges to local
      shallow ground water throughout the year, primarily because the local flow system
      is a regional low that lies perpendicular to the Franciscan Complex ground water
      flowpath. Little Stony Creek is a more prominent source of ground water in the
      wet season than in the dry season because Little Stony Creek flows continuously
      through the alluvial reach in the wet season and intermittently through the
      alluvial reach in the dry season. Extensive ground water withdrawals from the
      Franciscan Complex flow system could reduce the amount of water available to the
      local flow system, particularly during the dry season, and could substantially
      reduce the geographic extent of the regionally unique plant and wildlife
      habitats.

PMID- 12236270
TI  - Managing alleged performance problems--are we ready?

PMID- 12236271
TI  - Antibiotic treatment for cystitis.

PMID- 12236272
TI  - Boosting influenza immunisation for the over-65s.

PMID- 12236273
TI  - Boosting uptake of influenza immunisation: a randomised controlled trial of
      telephone appointing in general practice.
AB  - BACKGROUND: Immunisation against influenza is an effective intervention that
      reduces serologically confirmed cases by between 60% and 70%. Almost all
      influenza immunisation in the UK is done within general practice. Current
      evidence on the effectiveness of patient reminders for all types of immunisation
      programmes is largely based on North American studies. AIM: To determine whether
      telephone appointments offered bygeneral practice receptionists increase the
      uptake of irfluenza immunisation among the registered population aged over 65
      years in east London practices. DESIGN OF STUDY: Randomised controlled trial.
      SETTING: Three research general practices within the East London and Essex
      network of researchers (ELENoR). METHOD: Participants were 1,820 low-risk
      patients aged 65 to 74 years who had not previously been in a recall system for
      influenza immunisation at their general practice. The intervention, during
      October 2000, was a telephone call from the practice receptionist to intervention
      group households, offering an appointment for influenza immunisation at a nurse
      run. clinic Main outcome measures were the numbers of individuals in each group
      receiving immunisation, and practice costs of a telephone-appointing programme.
      RESULTS: intention to treat analysis showed an immunisation rate in the control
      group of 44%, compared with 50% in the intervention group (odds ratio = 1.29, 95%
      confidence interval = 1.03 to 1.63). Of the patients making a telephone
      appointment, 88% recieved immunisation, while 22% of those not wanting an
      appointment went on to be immunised. In the controlgroup, income generated was
      11.35 pounds per immunisation, for each additional immunisation in the
      intervention group the income was 5.20 pounds. The 'number needed to telephone'
      was 17. CONCLUSION: Uptake of influenza immunisation among the low-risk older
      population in inner-city areas can be boosted by around 6% using a simple
      intervention by receptionists. Immunisation rates in this low-risk group fell
      well short of the 60% government target. Improving immunisation rates will
      require a sustained public health campaign. Retaining the item-of-service
      payments to practices should support costs of practice-based interventions.

PMID- 12236274
TI  - Improving uptake of influenza vaccination among older people: a randomised
      controlled trial.
AB  - BACKGROUND: The uptake of influenza vaccination among older people is suboptimal.
      Contact with a doctor or nurse is associated with older people deciding to accept
      influenza vaccination. AIM: To compare different forms of approach in improving
      uptake of influenza vaccination among patients aged 75 years and over in primary
      care. DESIGN OF STUDY: Randomised controlled trial. SETTING: One large rural
      general practice serving the town and surrounding area of Melton Mowbray,
      Leicestershire. METHOD: All 2,052 patients aged 75 years and over, registered
      with the practice and not living in nursing/residential homes or sheltered
      accommodation, were included in the study. One-third of patients were randomised
      to receive an offer of influenza vaccination as part of an over-75 health check
      administered by a practice nurse in the patient's home, and two-thirds of
      patients were randomised to receive a personal letter of invitation to attend an
      influenza vaccination clinic held at the surgery. The main outcome measure was
      uptake of influenza vaccination. RESULTS: Six hundred and eighty patients were
      randomised to the health check arm of the trial and 1,372 were randomised to
      receive a personal letter. Of those randomised to the health check arm, 468
      received the health check from the nurse. Overall, the difference in influenza
      vaccination uptake was 6.4% (95% confidence interval [CI] = 2.2% to 10.4%) with
      67.9% (n = 932) of those who were sent a personal letter actually receiving the
      vaccine, compared with 74.3% (n = 505) of those offered a combined health check
      and influenza vaccination (P = 0.003). CONCLUSION: Combining home-based over- 75
      health checks with influenza vaccination can improve uptake among older patients.
      However this intervention is likely to be costly and its effect on influenza
      vaccination rates is modest. The difference in uptake is greater among those who
      do not routinely comeforwardfor vaccination and a more viable option may be to
      target these patients.

PMID- 12236275
TI  - Association between migraine and asthma: matched case-control study.
AB  - BACKGROUND: Earlier studies have suggested a link between asthma and severe
      headache, and also between migraine and wheezing illness. Recent analysis have
      also shown an increase of asthma among cases with a prior history of migraine but
      without a history of hay fever, allergic rhinitis or eczema. AIM: To examine
      whether there is an association between migraine and asthma in the United
      Kingdom. DESIGN OF STUDY: Matched case-control study using the General Practice
      Research Database (GPRD). SETTING: Practices in the United Kingdom providing data
      on 5,110,619 patients to the GPRD. METHOD: The subjects were the patients with
      one or more diagnoses of migraine plus treatment for migraine. Each case was
      matched by general practice, sex, and age, with one control who had never been
      given a diagnosis of migraine. Case and control groups were compared for
      prevalence of asthma, chronic obstructive pulmonary disease, respiratory symptoms
      treated with inhalers or hay fever. Investigations were carried out to determine
      whether the association between migraine and asthma was stronger among patients
      with hayfever or those without hayfever, and whether patients with migraine had
      an increased prescription of other (non-migraine and non-asthma) medications.
      RESULTS: Among 64 678 case-control pairs, the relative risk of asthma in patients
      with migraine was 1.59 (95% CI = 1.54 to 1.65) among definite cases, and 0.75
      (95% CI = 0.67 to 0.83) among those whose selection as case included beta-blocker
      prophylaxis. Among definite migraine cases, relative risks of chronic obstructive
      pulmonary disease, respiratory symptoms, eczema, and hay fever (pollinosis), were
      all raised (at 1.22, 1.85, 1.55, and 1.67, respectively). The association between
      migraine and asthma was stronger in patients without a diagnosis of hay fever,
      than in those with hayfever (relative risk = 1.32 and 1.19, respectively). The
      relative risk of prescription for a range of non-migraine, non-asthma medications
      was raised, the exception being anti-diabetic medication. CONCLUSION: This large
      case-control study provides evidence for an association between migraine and
      asthma. Frequent attendance at a general practice surgery may confound this
      association. However, if the association is real, its elucidation may help the
      understanding of disease mechanisms shared by migraine and asthma.

PMID- 12236276
TI  - Randomised controlled trial of nitrofurantoin versus placebo in the treatment of
      uncomplicated urinary tract infection in adult women.
AB  - BACKGROUND: Urinary tract infections (UTIs) are very common and have been treated
      with apparent success with antimicrobials for many years. However, there is a
      paucity of placebo-controlled clinical trials. AIM: To measure the symptomatic
      and bacteriological short-term effect of nitrofurantoin treatment versus placebo,
      in the treatment of uncomplicated UTI in adult non-pregnant women. DESIGN OF
      STUDY: Randomised placebo-controlled trial in general practice. SETTING: Non
      pregnant women, aged between 15 and 54 years old, consulting a general
      practitioner for symtoms suggestive of uncomplicated lower UTI and with pyuria
      (positive for leucocyte esterase test). METHOD: A dipslide was inoculated in
      first-void midstream urine and sent for examinion. The patients were randomised
      to receive nitrofurantoin 100 mg or placebo four times daily for three days.
      After three, seven, and 14 days a new dipslide was inoculated and symptoms of UTI
      were checked or improvement of symptoms and bacteriuria. RESULTS: Of 166 women
      consulting with symptoms suggestive for UTI, 78 had pyuia and agreed to
      participate in the study (the clinically suspected UTI group); of these, 40
      received nitrofurantoin and 38 received placebo. The result for combined
      symptomatic improvement and cure after three days was 27/35 in the nitrofurantoin
      group and 19/35 in the placebo group (c2 with Yates' correction P = 0.008; number
      needed to treat [NNT] = 4.4, 95% confidence interval [CI] = 2.3 to 79). After
      seven days, combined improvement and cure was observed in 30/34 and 17/33
      respectively (P = 0.003, NNT = 2.7, 95% CI = 1.8 to 6.0). At inclusion, 56 women
      had bacteriuria of > or = 10(5) CFU/ml (the bacteriologically proven UTI group).
      Of these, 29 received nitrofurantoin and 27 received placebo. After three days
      the bacteriological cure was 21/26 in the treatment group, compared with 5/25 in
      the placebo group (P < 0.001; NNT = 1.6, 95% CI= 1.2 to 2.6). After seven days
      the bacteriological cure rate was 17/23 in the intervention group and 9/22 in the
      placebo group (P = 0.05, NNT = 3, 95% CI = 1.7 to 17). CONCLUSION: In women with
      bacteriologically proven UTI, nitrofurantoin was significantly more effective
      than placebo in achieving bacteriological cure and symptomatic relief in just
      three days; this was still present after seven days. In patients with clinically
      suspected UTI the symptomatic effect was statistically significant after

PMID- 12236278
TI  - GPs' compliance with health and safety legislation and their occupational health
      needs in one London health authority.
AB  - This survey assessed general practitioners' (GPs') knowledge of and compliance
      with, health and safety legislation and occupational health guidance in one
      London health authority. The response rate was 85%. Although the majority of
      practices were aware of the most important piece of legislation--The Management
      of Health and Safety at Work Regulations, 1992--less than one in ten practices
      had carried out the required systematic risk assessments. Compliance with other
      health and safety legislation and related employment issues was also poor. The
      health of GPs and their staff may be at risk and these general practices may be
      vulnerable to prosecution by the Health and Safety Executive.

PMID- 12236279
TI  - Cardiovascular risk reduction in men: a nine-year cohort study.
AB  - Cardiovascular risk scores improved in a cohort of 500 males aged 20 to 50 years
      over a nine-year period. The major component of the risk improvement was a
      reduction in smoking habits. A disappointing finding is the increased number of
      obese subjects and those not participating in regular exercise. Altering these
      trends must now be a priority for all health professionals. The effects of
      community-based and primary care health promotion are likely to be synergistic
      with those of national mass media campaigns.

PMID- 12236277
TI  - Cluster randomised controlled trial of an educational outreach visit to improve
      influenza and pneumococcal immunisation rates in primary care.
AB  - BACKGROUND: Improvement in the delivery of influenza and pneumococcal
      vaccinations to high-risk groups is an important aspect of preventive care for
      primary healthcare teams. AIM: To investigate the effect of an educational
      outreach visit to primary healthcare teams on influenza and pneumococcal
      vaccination uptake in high-risk patients. DESIGN: Cluster randomised controlled
      trial. SETTING: Thirty general practices in the Trent region, UK. METHODS:
      Fifteen practices were randomised to intervention and 15 to the control group
      after stratifying for baseline vaccination rate. All intervention practices were
      offered and received an educational outreach visit to primary healthcare teams,
      in addition to audit and feedback directed at improving influenza and
      pneumococcal vaccination rates in high-risk groups. Control practices received
      audit and feedback alone. All practices measured influenza and pneumococcal
      vaccination rates in high-risk groups. Primary outcomes were improvements in
      vaccination rates in patients aged 65 years and over, and patients with coronary
      heart disease (CHD), diabetes and a history of splenectomy. RESULTS: Improvements
      in pneumococcal vaccination rates in the intervention practices were
      significantly greater compared with controls in patients with CHD, 14.8% versus
      6.5% (odds ratio [OR] = 1.23, 95% confidence interval [CI] = 1.13 to 1.34) and
      diabetes, 15.5% versus 6.8% (OR = 1.18, 95% CI = 1.08 to 1.29) but not
      splenectomy, 6.5% versus 4.7% (OR = 0.96, 95% CI = 0.65 to 1.42). Improvements
      for influenza vaccination were also usually greater in intervention practices but
      did not reach statistical significance. The increases for influenza vaccination
      in intervention versus control practices were for CHD, 18.1% versus 13.1% (OR =
      1.06, 95% CI = 0.99 to 1.12); diabetes, 15.5% versus 12.0% (OR = 1.07, 95% CI =
      0.99 to 1.16), splenectomy 16.1% versus 2.9% (OR = 1.22, 95% CI = 0.78 to 1.93);
      and those over 65 years 20.7% versus 25.4% (OR = 0.99, 95% CI = 0.96 to 1.02).
      CONCLUSION: Practices where primary care teams received an educational outreach
      visit demonstrated a significantly greater improvement in uptake in high-risk
      groups for pneumococcal but not influenza vaccine.

PMID- 12236280
TI  - Randomised controlled trials in primary care: scope and application.
AB  - There is now widespread acknowledgement of the absence of a sound evidence base
      underpinning many of the decisions made in primary care. Randomised controlled
      trials represent the methodology of choicefor determining efficacy and
      effectiveness of interventions, yet researchers working in primary care have been
      reluctant to use intervention studies, favouring observational study designs.
      Unfamiliarity with the different trial designs now available, and the relative
      advantages and disadvantages conferred by each, may be one factor contributing to
      this paradox. In this paper, we consider the principal trial designs available to
      primary care researchers, discussing the contexts in which a particular design
      may prove most useful. This information will, we hope, also prove useful to
      primary care clinicians attempting to interpret trial findings.

PMID- 12236282
TI  - Chronic fatigue syndrome/myalgic encephalitis.

PMID- 12236283
TI  - Chronic fatigue syndrome/myalgic encephalitis.

PMID- 12236281
TI  - Urinary tract infections in adult general practice patients.
AB  - Urinary tract infections (UTIs) are symptomatic infections of the urinary tract,
      mainly caused by the bacterium Escherichia coli. One in two women suffers from a
      UTI at least once in her life. The young and sexually active are particulaly
      affected, but it is also seen in elderly, postmenopausal women. The likelihood of
      recurrence is high. Diagnosis is made with regard to typical complaints and the
      presence of leucocytes and nitrites in the urine. A culture is unnecessary in
      most cases. Uncomplicated UTI should be distinguished from complicated UTI, which
      has a risk of severe illness. The treatment of choice--short-term therapy with
      trimethoprim or nitrofurantoin--is successful in over 80% of the cases. Co
      trimoxazol fluoroquinolones or cephalsporins are not considered first-choice
      drugs. There are indications that general practitioners' (GPs') management of UTI
      is not always optimal, specifically concerning diagnostic tests, the application
      of second-choice antibiotics, and the length of prescribed treatment courses.
      Many points relevant to GPs requirefurther research, such as epidemiology and
      resistance of urinary pathogens in the community and natural history of UTI, as
      well as optimal management in elderly or complicated patients and men.

PMID- 12236284
TI  - Chronic fatigue syndrome/myalgic encephalitis.

PMID- 12236285
TI  - GPs and child protection.

PMID- 12236286
TI  - New contract and career development.

PMID- 12236287
TI  - RCGP membership, icing on the cake?

PMID- 12236288
TI  - Frequent consulters.

PMID- 12236289
TI  - Poor performance?

PMID- 12236290
TI  - The power of statistics.

PMID- 12236291
TI  - General practice Down Under.

PMID- 12236292
TI  - Are GP leaders scared of sex?

PMID- 12236293
TI  - The end of the affair--public health medicine 1974-2002.

PMID- 12236294
TI  - RCGP 'virtual genetics' group meeting: 'the use of the family history in primary
      care'.

PMID- 12236295
TI  - An oral history of general practice 4: changing practice.

PMID- 12236296
TI  - Defining and cultivating the virtues.

PMID- 12236297
TI  - Beta interferon, NICE, and rationing.

PMID- 12236301
TI  - Tetanus--Puerto Rico, 2002.
AB  - During February-May 2002, the Puerto Rico Department of Health (PRDOH) received
      reports of three tetanus cases, two of which were fatal. The last reported case
      of tetanus in Puerto Rico had occurred in 1999. This report summarizes the
      investigations of these three cases, which underscore that health-care providers
      should ensure that all patients have been vaccinated fully against tetanus.

PMID- 12236302
TI  - Pertussis deaths--United States, 2000.
AB  - Pertussis (i.e., whooping cough) is associated typically with an inspiratory
      "whoop," prolonged paroxysmal cough, and posttussive vomiting; however, persons
      infected with Bordetella pertussis sometimes experience atypical symptoms, making
      prompt recognition difficult and probably increasing infection transmission. All
      infants aged <6 months and any infants who have not yet received 3 doses of
      diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine are
      especially vulnerable to B. pertussis infection. This report summarizes the
      investigations of two pertussis deaths that occurred in 2000. Clinicians should
      consider pertussis as a cause of illness, especially among vulnerable infants who
      present with cough illness, respiratory distress, or apnea. Timely diagnosis of
      pertussis in caregivers and other contacts of infants could prevent infant
      pertussis fatalities.

PMID- 12236303
TI  - Hepatitis B vaccination among high-risk adolescents and adults--San Diego,
      California, 1998-2001.
AB  - The national strategy to eliminate hepatitis B virus (HBV) transmission is based
      on 1) screening all pregnant women for hepatitis B surface antigen and post
      exposure vaccination of infants of infected mothers; 2) vaccinating all infants
      as part of the childhood vaccination schedule; 3) vaccinating children and
      adolescents not vaccinated previously; and 4) vaccinating adolescents and adults
      in groups at increased risk for infection. These strategies have been implemented
      successfully in the United States except for the vaccination of adults and older
      adolescents at high risk. This report describes the initial findings of a
      hepatitis B vaccination program for potentially high-risk adolescents and adults
      conducted in areas of San Diego County, California. The findings indicate that
      high rates of hepatitis B vaccination can be achieved in clinics and programs
      that serve persons at high risk for HBV infection through the integration of
      hepatitis B vaccination into routine preventive health-care services. Improved
      efforts to vaccinate adolescents and adults at increased risk for HBV infection
      are critical to reduce disease incidence and prevent chronic HBV infection.

PMID- 12236304
TI  - Evaluation of two post core systems using two different methods (fracture
      strength test and a finite elemental stress analysis).
AB  - The aim of this study was to compare a fiber composite laminate (FCL) post core
      and a conventional cast post core system by using two different methods. The
      first method was a conventional fracture strength test, and the second was a
      finite elemental stress-analysis method (FEM). For the conventional fracture
      strength test, 20 extracted, human upper, central incisors were used. The teeth
      were decoronated, treated endodontically, and restored with two post core
      systems. After embedding the samples in resin blocks, a loading force was applied
      to the teeth at a crosshead speed of 5 mm/ min at an angle of 45 degrees to the
      long axis of the tooth. The data were recorded, and the results were compared by
      using the Mann-Whitney U test. There was no statistically significant difference
      between the two post systems (p > 0.05). For FEM analysis, a pseudo three
      dimensional model of a maxillary central incisor, theoretically restored with
      either a cast post or an FCL, was used. The analysis was performed by using the
      structural analysis program (SAP90). FEM analysis showed that stress was
      accumulated within the cast post core system, and transmission of stress to
      supportive structures and the tooth was low. This is an advantage for tooth and
      supporting tissues. When the FCL post core system was evaluated by FEM, the
      results indicated that this system transferred stress to supportive structures
      and the tooth while stress accumulation within the post system was low. This is
      an advantage for the restoration but disadvantage for the supporting tissues.

PMID- 12236305
TI  - Inactivation of the antibacterial activity of iodine potassium iodide and
      chlorhexidine digluconate against Enterococcus faecalis by dentin, dentin matrix,
      type-I collagen, and heat-killed microbial whole cells.
AB  - The antibacterial activity of chlorhexidine digluconate and iodine potassium
      iodide on Enterococcus faecalis A197A was tested in the presence of dentin,
      dentin matrix, dentin pretreated by EDTA and citric acid, collagen, and heat
      killed cells of Enterococcus faecalis and Candida albicans. Medications were
      preincubated for 1 h with each of the potential inhibitors and tested for their
      antibacterial activity against E. faecalis, strain A197A. Surviving bacteria were
      sampled after 1 and 24 h of incubation. Dentin matrix and heat-killed microbial
      cells were the most effective inhibitors of chlorhexidine, whereas dentin
      pretreated by citric acid or EDTA showed only slight inhibition. Dentin and skin
      collagen showed some inhibition at 1 h but not after 24 h. Iodine potassium
      iodide was effectively inhibited by dentin, dentin matrix, and heat-killed
      microbial cells. Skin collagen and dentin pretreated by EDTA or by citric acid
      showed little or no inhibitory effect on iodine potassium iodide. Different
      components of dentin are responsible for the divergent patterns of inhibition of
      the antibacterial activity of chlorhexidine digluconate and iodine potassium
      iodide. Chemical treatment of dentin before applying the medication into the root
      canal may alter the antibacterial effect of the medication.

PMID- 12236306
TI  - Effect of three different sealers on the sealing ability of both thermafil
      obturators and cold laterally compacted Gutta-Percha.
AB  - The purpose of this study was to assess the seal obtained in straight and curved
      root canals filled with either laterally compacted gutta-percha or Thermafil
      obturators. Each technique was used in combination with three different sealers
      (RSA RoekoSeal, AH Plus, AH 26). Thermafil obturators were also used without
      sealer, resulting in a total of 14 test groups of 16 teeth each. Sixty teeth
      served as positive or negative controls. Included in the study were 142 extracted
      teeth with straight and 142 with curved root canals. All canals were enlarged up
      to size 40. After obturation, all roots were placed in India ink for 48 h and
      rendered transparent to measure the maximum linear dye penetration. Canals filled
      with Thermafil obturators had significantly more extrusion of filling material
      than canals filled by lateral compaction (p < 0.01). Thermafil without sealer
      showed significantly greater dye penetration compared with all other groups both
      in straight and in curved canals (p < 0.05). As long as a sealer was used, the
      seal obturated with Thermafil was equivalent in terms of dye penetration to
      lateral compaction. There were no statistical differences in the mean apical dye
      penetration among the three sealers. The differences between the dye penetration
      in straight and in curved canals were insignificant for all groups (p > 0.05).
      Under the conditions of this study, Thermafil obturators achieved seals
      comparable to lateral compaction, as long as a sealer was used.

PMID- 12236307
TI  - Periapical lesion development in rats inhibited by dexamethasone.
AB  - Bone resorption is one of the hallmarks of inflammatory periapical lesions and is
      mediated by cytokines. Recent insights into the immunobiology of these lesions
      indicate that pharmacological modulation of their bone resorbing activity may be
      possible. Periapical lesions were induced in rats by occlusal exposure of the
      pulps of their lower first molars. The size of the resulting lesions was followed
      up and evaluated by image analysis of their radiographs. The lesions increased
      with time, and the average area of their radiographic images reached 2.18 (+/-
      0.33) mm2 by day 21. Systemic dexamethasone treatment (0.5 mg/kg, every third
      day) inhibited the growth of the periapical lesions, which reached an average
      area of 1.63 (+/- 0.30) (p < 0.01). These results support the hypothesis that
      bone resorption in periapical inflammatory lesions may be pharmacologically down
      regulated.

PMID- 12236308
TI  - Effect of sonic and ultrasonic retrograde cavity preparation on the integrity of
      root apices of freshly extracted human teeth: scanning electron microscopy
      analysis.
AB  - Sonic and ultrasonic root-end preparation devices permit the preparation of
      conservative and straight cavities. However, microfractures and marginal chipping
      can occur due to the vibratory action of such instruments. The purpose of this
      study was to evaluate the effect of retrograde preparations by using sonic and
      ultrasonic tips on the integrity of root-end surfaces. Eighty, human anterior
      teeth were grouped according to size and treated as follows: treatment 1: root
      end resection (RR) and root-end cavity preparation (RP) with KIS ultrasonic
      retrotip; treatment 2: RR and RP with Satelec S12/90 (no diamond coating)
      ultrasonic retrotip; treatment 3: RR and RP with a diamond-coated retrotip
      attached to a sonic device (Sonics); treatment 4: RR and RP with Satelec S12/90D
      (diamond coated) ultrasonic retrotip. The root-end surface topographies were
      assayed by means of polyvinylsiloxane impressions and epoxy resin replicas. SEM
      pictures of each sample were taken before and after preparation, and the images
      were evaluated by using an image processing and analysis system. The parameters
      evaluated were shape quality, presence of cracks, and marginal chipping. The
      results showed no statistically significant differences among anatomic groups,
      treatments, or tooth sizes (p > 0.05). Because treatment 3 removed more dental
      structure than the others did, its use on small teeth is inadvisable.

PMID- 12236309
TI  - Evaluating IL-2 levels in human pulp tissue.
AB  - In murine and human CD4+ T cell populations, there are three subpopulations of T
      helper cell types. Hahn et al. demonstrated the ratio of CD4/ CD8 + cells
      significantly increases in inflamed dental pulps compared with normal pulps.
      Elevated levels of interleukin (IL)-2 have been detected in inflamed dental pulps
      and the level of IL-2 could be used as a marker for inflammation. In this study,
      levels of IL-2 were evaluated by using a human IL-2 cytokine assay kit on 80
      samples of freshly extracted human pulp tissue. Applying standard diagnostic
      procedures, the tissue samples were clinically categorized into one of three
      experimental groups. The results demonstrated that there were no significant
      differences between the concentrations of IL-2 in any of the experimental groups.
      Our findings are different from results reported previously. Further
      investigation is warranted to determine if a correlation exists between the
      concentration of IL-2 or other interleukins and the degree of inflammation
      present in the dental pulp.

PMID- 12236310
TI  - Comparison of endodontist versus generalist regarding preference for
      postendodontic use of cotton pellets in pulp chamber.
AB  - A degree of uncertainty exists about the use of cotton pellets in the pulp
      chamber after canal obturation. The purpose of this study was to poll practicing
      endodontists and generalists regarding their preference. Forty-six endodontists
      and an equal number of general dentists were polled in a mail survey regarding
      their preferences for the use of a cotton pellet in the pulp chamber after canal
      obturation. Eighty-seven percent of the endodontists and 54% of the generalists
      responded. Of the endodontists, 62.5% said they thought that the general dentist
      wanted a cotton pellet, contrasted to 80% of the generalists. The difference in
      proportions was not statistically significant.

PMID- 12236311
TI  - The quality of apical canal preparation using hand and rotary instruments with
      specific criteria for enlargement based on initial apical file size.
AB  - The aim of this study was to compare the quality of apical enlargement of
      mesiobuccal canals of mandibular molars using conventional stainless steel hand
      files (K files) and nickel-titanium (Ni-Ti) rotary instruments (LightSpeed).
      Thirty freshly extracted mandibular molars were randomly assigned to three equal
      groups (n = 10 each group). The mesiobuccal canals were instrumented with K file
      using step-back technique without coronal flaring (control; group 1), K file
      using step-back technique after coronal flaring (group 2), and LightSpeed
      instrumentation (group 3). Specific criteria for apical enlargement based on
      initial apical size were used. For step-back techniques, the master apical file
      sizes were based on the Grossman criterion of three sizes larger than the first
      file that bound at working length, without coronal flaring (group 1) and with
      flaring (group 2). For the LightSpeed (LS) group, the master apical rotary sizes
      were based on the manufacturer's recommendation. Canal cleanliness, canal
      transportation, and final canal shapes were determined histologically at 1-mm and
      3-mm levels short of the working length. Canals were prepared to significantly
      larger sizes using LS instrumentation than with either hand instrumentation
      techniques (15-17 ISO units, p < 0.001). LS instrumentation allowed greater
      apical enlargement with significantly cleaner canals, less apical transportation,
      and better canal shape than both hand instrumentation groups at both levels (p <
      0.05). None of the three techniques was totally effective in cleaning the apical
      canal space. It was concluded that greater apical enlargement using LS rotary
      instruments is beneficial as an attempt to further debride the apical third
      region in mesiobuccal canals of mandibular molars. Instrument designs, alloy
      properties, and canal curvature are important factors that determine the
      feasibility of greater apical enlargement in narrow canals.

PMID- 12236312
TI  - A comparison of fill density obtained by supplementing cold lateral condensation
      with ultrasonic condensation.
AB  - The purpose of this study was to compare quantitatively the density of gutta
      percha root canal fillings produced by cold lateral condensation with those
      produced by an ultrasonically energized spreader in a warm lateral condensation
      technique in artificial root canals. Thirty-degree simulated root canals in 30
      transparent acrylic blocks were instrumented by using rotary files. The blocks
      were weighed. The canals were obturated with gutta-percha using cold lateral
      condensation without sealer and then weighed again. Two applications of warm
      lateral condensation were then performed on the same 30 canals using the UES. The
      blocks were weighed once more after each additional UES obturation treatment. The
      first heat application produced a 26.92% increase in weight over lateral
      condensation, and the second heat application produced an additional 5.95%
      increase. A one-way repeated measures ANOVA followed by the Tukey-Kramer test
      revealed that both applications of warm lateral condensation produced significant
      (p < 0.001) increases in weight. Results indicate that warm lateral condensation
      using a ultrasonically energized spreader results in denser gutta-percha fills by
      weight than cold lateral condensation.

PMID- 12236313
TI  - Sports Dentistry For Endodontists.

PMID- 12236314
TI  - Effect of deposited lipids in atheromatous lesions on the migration of vascular
      smooth muscle cells.
AB  - In advanced atherosclerotic lesions, a decrease in smooth muscle cells is
      observed in the cap tissue. This causes the thinning of the cap, and may lead to
      plaque rupture. We studied the effect of deposited lipids on the migration of
      vascular smooth muscle cells, and identified the main cause of the effect. The
      lipids were extracted from atherosclerotic lesions in the human aorta at autopsy,
      and separated into three fractions with a Sep-Pak ODS cartridge. Then, each
      fraction was added to the lower part of a chemotaxis chamber, and cultured
      vascular smooth muscle cells to the upper part. After 4 hours incubation, the
      cells that had migrated to the opposite side were counted. The oxysterol-rich
      fraction (10 microg/ml) inhibited the migration, whereas the cholesterol ester
      and free cholesterol fractions did not. Finally, we tested the pure oxysterols, 7
      ketocholesterol and 27-hydroxycholesterol. Both inhibited migration, whereas the
      free cholesterol and cholesterol ester did not. Oxysterols generated in the lipid
      pool might inhibit the migration of smooth muscle cells.

PMID- 12236315
TI  - Sweet elements of Siraitia grosvenori inhibit oxidative modification of low
      density lipoprotein.
AB  - This study examined the ability of sweet elements extracted from Siraitia
      grosvenori (SG) to inhibit the oxidation of LDL. We monitored the formation of
      conjugated diene during copper-mediated LDL oxidation in the presence or absence
      of sweet elements of whole extract of SG (SG extract) or cucurbitane glycosides
      (CGs) purified from SG extract as sweet elements. CGs consist of Mogroside IV
      (Mog.IV), Mogroside V (Mog.V), 11-Oxo-mogroside V (11-Oxo-mog.V), and Siamenoside
      I (Sia.I). In addition, the effect of these elements on human umbilical vein
      endothelial cell (HUVEC)- mediated LDL oxidation was tested by measuring
      production of lipid peroxides. SG extract inhibited copper-mediated LDL oxidation
      in a dose-dependent fashion, but neither glucose nor erythritol suppressed the
      oxidation. Among CGs, 11-Oxo-mog.V significantly inhibited LDL oxidation, and
      prolongation of the lag time during LDL oxidation by 11-Oxo-mog.V was dose
      dependent. The lag time (119.7 +/- 8.9 min) in the presence of 200 microM 11-Oxo
      mog.V was significantly longer than that (76.8 +/- 5.5 min) of control (p <
      0.01). In addition, SG extract and 11-Oxo-mog.V inhibited HUVEC-mediated LDL
      oxidation in a dose-dependent manner. These results demonstrate that SG extract
      can inhibit LDL oxidation and that 11-Oxo-mog.V, a sweet element of SG extract,
      provides the anti-oxidative property of SG which might reduce the atherogenic
      potential of LDL.

PMID- 12236316
TI  - An association between plasma homocysteine concentrations and ischemic stroke in
      elderly Japanese.
AB  - The present study was performed to clarify the relation between plasma
      homocysteine and ischemic stroke. We studied the relationship between ischemic
      stroke and the known risk factors for atherosclerosis including plasma
      homocysteine in 91 in-patients (80.3 +/- 6.8 years) in a medical ward. Those
      diagnosed with transient ischemic attack, cerebral infarction were placed in the
      disease group. Blood was drawn from in-patients in a fasting state for
      determination of plasma homocysteine. Plasma homocysteine concentrations were
      determined using a high-performance liquid chromatography assay. The odds ratio
      of ischemic stroke was higher in the second (10.0-13.9 micromol/l) and third
      highest plasma homocysteine concentration groups (> or = 14.0 micromol/l) than in
      the first group (< 10.0 micromol/l) by 5.18 and 4.42-fold, respectively. Logistic
      regression analysis using ischemic stroke as an object variable, adjusted by
      various risk factors including the plasma homocysteine concentration showed that
      the odds ratio on combining the second and third groups was 5.80 (95% confidence
      interval (Cl): 1.50-22.5) compared with the first group. The findings confirmed
      that the association between plasma homocysteine concentration and ischemic
      stroke in Western populations is also present among the elderly Japanese.

PMID- 12236317
TI  - Fenofibrate, a peroxisome proliferator-activated receptor alpha activator,
      suppresses experimental autoimmune myocarditis by stimulating the interleukin-10
      pathway in rats.
AB  - Experimental autoimmune myocarditis (EAM) in rats is an animal model of human
      giant cell myocarditis and postmyocarditis dilated cardiomyopathy. As the heart
      consumes large amounts of energy, heart diseases such as myocarditis and dilated
      cardiomyopathy are associated with abnormal fatty acid metabolism. Peroxisome
      proliferator-activated receptor alpha (PPARalpha) is a regulator of the oxidative
      degradation of fatty acids. To investigate the role of PPARalpha in EAM,
      fenofibrate (a PPARalpha activator) was administered to rats with EAM for 4
      weeks. Reductions in the ratios of both ventricular weight to body weight and the
      area of inflammatory lesions to the total area of heart sections were observed in
      fenofibrate-treated rats when compared with controls. Fenofibrate ameliorated
      changes in serum albumin and sialic acid, which are markers of inflammation.
      Cardiac expression of interleukin-10 (IL-10) mRNA was more pronounced in the
      fenofibrate group than in the control group (1.3 +/- 0.2 vs 0.7 +/- 0.1; p <
      0.01), and the area of intact myocardium correlated with the IL-10 mRNA level (p
      = 0.0297, r = 0.620). We suggest that PPARalpha activators may prevent the
      progression of myocarditis through increased expression of the gene encoding the
      anti-inflammatory cytokine IL-10, although the mechanisms involved remain to be
      determined.

PMID- 12236318
TI  - Immunohistochemical localization and mRNA expression of apolipoprotein A-I in rat
      spinal cord.
AB  - Apolipoproteins in the cerebrospinal fluid (CSF) play important roles in lipid
      metabolism in the central nervous system. Although it has been demonstrated that
      apo E is synthesized in the neuron, the synthesis of apo A-I has only been
      determined in fish and chicken. It was demonstrated that apo A-I concentrations
      in the CSF were increased in poliovirus-infected macaques, however, the origin of
      the CSF apo A-I was not determined. The present immunohistochemical study
      provided evidence that apo A-I was localized within the nerve cell body of the
      rat spinal cord. In situ hybridization also showed that apo A-I mRNA was
      predominantly expressed in the neurons. As a further experiment, we compared apo
      A-I levels in the spinal cord from control rats and rats with experimental
      allergic encephalomyelitis (EAE), which was induced by sensitization with myelin
      basic protein. Although no significant changes in serum apo A-I levels were
      observed, apo A-I levels in the spinal cord were significantly elevated in EAE
      rats. Furthermore, apo A-I in the spinal cord of rats with EAE was not seen in
      the nerve cell body, but at the interstitium, particularly in lesions where
      inflammation had occurred. The current study clearly demonstrated that apo A-I is
      synthesized in the neurons of the rat spinal cord and the synthesis was
      suppressed in EAE rats.

PMID- 12236319
TI  - Prognosis of hypercholesterolemic patients taking pravastatin for five years: the
      Chiba Lipid Intervention Program (CLIP) Study.
AB  - The Chiba Lipid Intervention Program (CLIP) Study was designed to clarify the
      prognosis of Japanese hypercholesterolemic patients taking pravastatin for 5
      years. Hypercholesterolemic patients (n = 2,529) with a total cholesterol level >
      or = 220 mg/dl and without histories of ischemic coronary heart disease and/or
      cerebral infarction were administered pravastatin (10-20 mg/day). Among them,
      2,131 took pravastatin fully (Pravastatin-continued group), and 398 discontinued
      the treatment (Discontinued group). The baseline total cholesterol level was
      264.3 +/- 34.7 mg/dl (mean +/- standard deviation). The mean reduction rates of
      total cholesterol and low-density lipoprotein (LDL) cholesterol were 18.0% and
      27.2%, respectively. Mild and moderate adverse events occurred in 86 cases
      (3.6%). Serious adverse events were not observed. Death rates of the pravastatin
      continued group and of the discontinued group were 2.6 and 16.0/1,000
      persons/year, respectively. Cardiac events (fatal and nonfatal myocardial
      infarction, cardiac death, angina pectoris) in all, occurred in 35 patients
      (incidence rate = 2.77/1,000 persons/year). In the pravastatin continued group, 9
      causes of fatal and nonfatal myocardial infarction occurred (0.84/1,000
      persons/year), whereas in the discontinued group, 4 cases occurred (2.06/1,000
      persons/ year). The risk ratio for cardiac events was correlated with the number
      of risks. In the low-risk group (< or = 1 risk), decreased rates of LDL
      cholesterol were less in the cardiac event group than the non-cardiac event group
      (LDL-cholesterol; 16% vs 25%, p = 0.04). These results suggested the following;
      1) Pravastatin maintained a cholesterol lowering effect long-term without serious
      complications. 2) Pravastatin administration might reduce the mortality rate and
      myocardial infarction. 3) The combination of multiple risks is a strong factor
      for a cardiac event in addition to hypercholesterolemia.

PMID- 12236320
TI  - The functional significance of ERP effects during mental rotation.
AB  - In a parity judgment task, the ERPs at parietal electrode sites become more
      negative as more mental rotation has to be executed. This article provides a
      review of the empirical evidence regarding this amplitude modulation. More
      specifically, experiments are reported that validate both the functional
      relationship between mental rotation and the amplitude modulation as well as the
      temporal relationship both in single- and in dual-task situations. Additionally,
      ERP effects are reported in the psychological refractory period (PRP) paradigm
      with mental rotation as the second task. Finally, unresolved issues are discussed
      that, I hope, might stimulate future research.

PMID- 12236321
TI  - Guidelines for mechanical lung function measurements in psychophysiology.
AB  - Studies in psychophysiology and behavioral medicine have uncovered associations
      among psychological processes, behavior, and lung function. However,
      methodological issues specific to the measurement of mechanical lung function
      have rarely been discussed. This report presents an overview of the physiology,
      techniques, and experimental methods of mechanical lung function measurements
      relevant to this research context. Techniques to measure lung volumes, airflow,
      airway resistance, respiratory resistance, and airflow perception are introduced
      and discussed. Confounding factors such as ventilation, medication, environmental
      factors, physical activity, and instructional and experimenter effects are
      outlined, and issues specific to children and clinical groups are discussed.
      Recommendations are presented to increase the degree of standardization in the
      research application and publication of mechanical lung function measurements in
      psychophysiology.

PMID- 12236322
TI  - Influence of fitness and gender on blood pressure responses during active or
      passive stress.
AB  - We examined hemodynamic and autonomic components of blood pressure responses
      during active and passive stressor tasks in a sample of young, normotensive men
      and women who were physically active but differed on fitness (i.e., VO2peak).
      During the hand cold pressor, increases in systolic blood pressure were inversely
      related to fitness among women but not men. Regardless of gender, fitter
      participants had a greater increase in cardiac pace during mental arithmetic,
      coherent with a decreased cardiac-vagal component of heart rate variability, and
      a greater compensatory reduction in stroke volume. Fitness was otherwise
      unrelated to changes in cardiac output and vascular resistance during the
      stressor tasks. Our findings suggest that cardiorespiratory fitness augments the
      cardiac-vagal withdrawal that is characteristic of mental arithmetic. The blunted
      systolic blood pressure response to the hand cold pressor among fitter women
      suggests that cardiorespiratory fitness should be considered as a covariate in
      studies that examine the hand cold pressor as a predictor of future hypertension
      among women.

PMID- 12236323
TI  - Hypersensitivity to acoustic change in children with autism: electrophysiological
      evidence of left frontal cortex dysfunctioning.
AB  - Exaggerated reactions to even small changes in the environment and abnormal
      behaviors in response to auditory stimuli are frequently observed in children
      with autism (CWA). Brain mechanisms involved in the automatic detection of
      auditory frequency change were studied using scalp potential and scalp current
      density (SCD) mapping of mismatch negativity (MMN) in 15 CWA matched with 15
      healthy children. Compared with the response in controls, MMN recorded at the Fz
      site in CWA showed significantly shorter latency and was followed by a P3a wave.
      Mapping of potentials indicated significant intergroup differences. Moreover, SCD
      mapping demonstrated the dynamics of the different MMN generators: Although
      temporal component was evidenced bilaterally in both groups, it occurred earlier
      on the left hemisphere in CWA, preceded by an abnormal early left frontal
      component. The electrophysiological pattern reported here emphasized a left
      frontal cortex dysfunctioning that might also be implicated in cognitive and
      behavioral impairment characteristic, of this complex neurodevelopmental
      disorder.

PMID- 12236324
TI  - Shifting hemodynamics of blood pressure control during prolonged mental stress.
AB  - The present study examined the hemodynamics underlying blood pressure elevations
      for evidence of a shift in the control of blood pressure during prolonged mental
      stress. Mean arterial pressure (MAP), cardiac output (CO), and total peripheral
      resistance (TPR) were measured at rest, during a 28-min mental arithmetic stress
      task, and during recovery, in 30 young healthy men and women. The stress task
      elicited a sustained increase in MAP: CO rose during the first half of the task
      but returned to baseline levels during the last quarter of the task, whereas TPR
      increased as the task progressed. When participants' hemodynamic reactions were
      classified as cardiac, vascular, or neither, there were more cardiac reactors
      early relative to late in the task, whereas there were more vascular reactors
      late relative to early. Thus, the sustained pressor response was initially
      supported mainly by cardiac mechanisms but subsequently by predominantly vascular
      mechanisms.

PMID- 12236325
TI  - Influence of control and physical effort on cardiovascular reactivity to a video
      game task.
AB  - This study investigated the influences of both perceived control and physical
      effort on cardiovascular reactivity. Undergraduates (N = 32) played a video game
      task interrupted by aversive noise. Perceived control of the noise was
      manipulated by instructions indicating the presence or absence of a contingency
      between performance and noise presentations. Physical effort was manipulated by
      controlling the physical force required to perform the task. There was a
      significant main effect of control on systolic blood pressure (SBP) and total
      peripheral resistance (TPR), with both increasing more during low than high
      control conditions. The results suggest that high perceived control over aversive
      noise in an effortful task reduces SBP and TPR reactivity relative to low
      perceived control. The results are consistent with the idea that control buffers
      the reactivity associated with task performance under aversive conditions.

PMID- 12236326
TI  - Deficits in automatically detecting changes in conjunction of auditory features
      in patients with schizophrenia.
AB  - Disturbances in processing simple acoustic changes in a stream of stimuli have
      been widely reported in patients with schizophrenia, but little is know about
      auditory feature conjunction in these individuals. This study was designed to
      examine the extent to which patients with schizophrenia automatically process
      changes in conjunction of auditory features by using event-related brain
      potentials. Seventeen patients and 17 age-matched controls were presented with
      frequent low pitch tones at 45 degrees to the left of center and frequent high
      pitch tones at 45 degrees to the right of center while performing a continuous
      visual serial-choice reaction time task. The sequence of auditory stimuli
      included rare conjunction-deviants comprised of a different combination of
      features (e.g., low pitch tone at 45 degrees right) and double-deviant tones that
      differed from the standard tones in both pitch and location (i.e., middle pitch
      at 0 degrees azimuth). Conjunction-deviant stimuli elicited an MMN wave that was
      maximum at frontocentral sites. Compared with controls, the MMN to conjunction
      deviant was reduced in patients and was more centrally distributed. Double
      deviant sounds generated a biphasic MMN followed by a P3a wave at central sites.
      Both MMN and P3a were reduced in patients compared with controls. These results
      show that patients with schizophrenia have difficulty in automatically detecting
      changes in a combination of auditory features as well as orienting to what
      "normally" would be considered salient by healthy individuals.

PMID- 12236327
TI  - Tracking eye fixations with electroocular and electroencephalographic recordings.
AB  - We describe a method, based on recordings of the electroencephalogram (EEG) and
      eye movement potentials (electrooculogram), to track where on a screen (x,y
      coordinates) an individual is fixating. The method makes use of an empirically
      derived beam-forming filter (derived from a sequence of calibrated eye movements)
      to isolate eye motion from other electrophysiological and ambient electrical
      signals. Electrophysiological researchers may find this method a simple and
      inexpensive means of tracking eye movements and a useful complement to scalp
      recordings in studies of cognitive phenomena. The resolution is comparable to
      that of many commercial systems; the method can be implemented with as few as
      four electrodes around the eyes to complement the EEG electrodes already in use.
      This method may also find some specialized applications such as studying eye
      movements during sleep and in human-machine interfaces that make use of gaze
      information.

PMID- 12236328
TI  - Consolidation of psychophysiology as a scientific discipline, 1930-1964: a
      historical note.
AB  - The ground covered by psychophysiology throughout the decades prior to its
      constitution as an independent discipline has not been well documented, despite
      its historical interest. A bibliometric study of the research published in
      scientific journals by 66 of the most relevant psychophysiologists from 1930 to
      1964, analyzing the contents of the records indexed in the PsycINFO database,
      gives us an image of the state of the emergent discipline during that period.
      This study reveals that this was a period of consolidation, marked by the
      refinement of instruments and procedures, the characterization of measurements,
      and the establishment of the basic relationships between physiological and
      psychological variables, the development and validation of basic constructs such
      as activation, or interest in the study of psychopathology. In these years the
      foundations of psychophysiology were laid, leading to the formalization of the
      discipline at the end of the period.

PMID- 12236329
TI  - Effects of perceptual context on event-related brain potentials during auditory
      spatial attention.
AB  - The effects of auditory spatial attention on event-related brain potentials
      (ERPs) were examined in situations that promoted stream segregation. Short and
      long noise bursts were presented at three azimuth locations and listeners were
      asked to respond to the longer sounds occurring at either the right- or left-most
      location. In the baseline condition, the three sound sources were evenly spaced
      apart. In the distractor clustering conditions, middle and far sounds were
      clustered. In the attended clustering conditions, middle and attended sounds were
      clustered. ERP indices of attention, isolated as negative difference (Nd) waves,
      were greater over the hemisphere contralateral to the attended location. Nd waves
      were also larger when the middle sounds were moved toward the far distractors,
      consistent with an object-based gradient of auditory attention in which higher
      order information provided by the perceptual context influences selective
      processing.

PMID- 12236330
TI  - Variability in AC amplifier distortions: estimation and correction.
AB  - AC amplifiers can introduce significant distortions into the low frequency and DC
      components of recorded electrophysiological data such as event-related potentials
      (ERPs). Methods for correcting such distortions (i.e., estimating the waveform of
      the original data) after the data have been amplified and recorded rely on an
      accurate estimate of the amplifier's time constant (TC). We show that the filter
      characteristics of AC amplifiers in at least some commercially available ERP
      recording instruments may vary considerably across individual channels, even when
      each houses an identical AC amplifier circuit. Clearly, distortion correction
      methods must take this variability into account. We propose an empirical means of
      estimating the correct TC value. This approach yields more accurate correction
      than those based on TCs calculated analytically.

PMID- 12236331
TI  - Large-scale neural correlates of affective picture processing.
AB  - Hemodynamic and electrophysiological studies indicate differential brain response
      to emotionally arousing, compared to neutral, pictures. The time course and
      source distribution of electrocortical potentials in response to emotional
      stimuli, using a high-density electrode (129-sensor) array were examined here.
      Event-related potentials (ERPs) were recorded while participants viewed pleasant,
      neutral, and unpleasant pictures. ERP voltages were examined in six time
      intervals, roughly corresponding to P1, N1, early P3, late P3 and a slow wave
      window. Differential activity was found for emotional, compared to neutral,
      pictures at both of the P3 intervals, as well as enhancement of later posterior
      positivity. Source space projection was performed using a minimum norm procedure
      that estimates the source currents generating the extracranially measured
      electrical gradient. Sources of slow wave modulation were located in occipital
      and posterior parietal cortex, with a right-hemispheric dominance.

PMID- 12236332
TI  - The impact of reinforcement density on response differentiation in configural
      discrimination problems.
AB  - Two human Pavlovian conditioning experiments investigated the impact of
      reinforcement density (the number of reinforced trials divided by the total
      number of trials) on discrimination learning. Experiment 1 used a negative
      patterning problem (A+, B+, AB-) and Experiment 2 used a positive patterning
      problem (A-, B-, AB+). In both experiments, reinforcement density varied across
      four levels. Response differentiation between reinforced and non-reinforced
      stimuli was linearly related to the decrease in reinforcement density. Responses
      to nonreinforced stimuli did not differ between the four groups in either
      experiment. In contrast to this, responses to reinforced stimuli were
      considerably more pronounced in conditions with lower reinforcement density. For
      negative patterning, this replicates and extends similar observations from other
      species. For positive patterning, this is a finding that has not yet been
      reported in other experiments. The results are in agreement with the comparator
      hypothesis (Miller & Matzel, 1988) and with Wagner's (1981) "standard operating
      procedures" (SOP) model.

PMID- 12236333
TI  - Effects of musical expertise on the early right anterior negativity: an event
      related brain potential study.
AB  - Event-related brain potentials in response to harmonically inappropriate chords
      were compared for musical experts and novices. Similar to previous studies, these
      chords elicited an early right anterior negativity (ERAN). The amplitude of the
      ERAN was clearly larger for musical experts than for novices, presumably because
      experts had more specific musical expectancies than novices. Chords with a
      physically deviant timbre elicited a mismatch negativity that did not
      differentiate the groups, indicating that the larger ERAN in experts was not due
      to a general enhanced auditory sensitivity. The ERAN reflects fast and automatic
      neural mechanisms that process complex musical (music-syntactic) irregularities,
      and the present results indicate that these mechanisms can be modulated by
      expertise.

PMID- 12236334
TI  - Error rate on the antisaccade task: heritability and developmental change in
      performance among preadolescent and late-adolescent female twin youth.
AB  - We examined heritability of error rate on the antisaccade task among female twin
      youths. This task appears to be sensitive to prefrontal functioning, providing a
      measure of individual differences in inhibitory control associated with genetic
      risk for schizophrenia. The sample consisted of 674 11-year-olds and 616 17-year
      olds, comprising the two cohorts of female twins from the Minnesota Twin Family
      Study, a population-based investigation of substance abuse and related
      psychopathology. We used biometric model-fitting methods to determine the
      relative magnitude of genetic and environmental influences on performance. In
      both age cohorts, the best fitting model contained additive genes and nonshared
      environment. Despite substantial age-related differences in mean performance
      levels (effect size = .81), additive genes accounted for greater than half the
      variance in performance in both age cohorts. These results are consistent with
      the hypothesis that antisaccade error rate might serve as an endophenotype for
      behavior disorders reflecting frontal lobe dysfunction or problems with
      inhibitory control.

PMID- 12236335
TI  - Influence of a monetary incentive upon attentional modification of short-lead
      prepulse inhibition and long-lead prepulse facilitation of acoustic startle.
AB  - Short-lead prepulse inhibition and long-lead prepulse facilitation of startle are
      greater during attended than ignored prestimuli. The present work examined
      whether this attentional modification is influenced by monetary incentive.
      Participants (43 college students) were randomly assigned to receive a small
      performance-based monetary incentive or were instructed to try their best. The
      task was to judge the duration of tones of one of two pitches during a series of
      48 tones. Prepulse inhibition of startle eyeblink EMG was assessed at 60, 120,
      and 240 ms, and prepulse facilitation was assessed at 4,500 ms following tone
      onset. Short-lead percent prepulse inhibition was greater during attended than
      ignored prestimuli only at 120 ms among paid participants. Long-lead prepulse
      facilitation was greater for attended than ignored tones, but this effect did not
      vary with incentive condition. This study demonstrates that attentional
      modification of short-lead prepulse inhibition is sensitive to a monetary
      incentive and provides a basis for further examination of motivational effects on
      early attentional processing.

PMID- 12236336
TI  - The human nociceptive flexion reflex threshold is higher during systole than
      diastole.
AB  - A baroreflex mechanism may explain hypertensive hypoalgesia. At rest, arterial
      baroreceptors are stimulated during the systolic upstroke of the pressure pulse
      wave. This study examined the effects of naturally occurring variations in
      baroreceptor activity during the cardiac cycle on an objective measure of pain,
      the nociceptive flexion reflex (NFR). Two interleaved up-down staircase
      procedures determined separate NFR thresholds during systole and diastole in 36
      healthy, normotensive young adults. On odd-numbered trials, the sural nerve was
      stimulated electrocutaneously at R + 300 ms whereas on even-numbered trials,
      stimulation was delivered at R + 600 ms. The NFR threshold was higher at R + 300
      ms than R + 600 ms. In contrast, stimulus intensity ratings did not differ
      between R + 300 ms and R + 600 ms. Stimulation of baroreceptors by natural
      increases in blood pressure during the systolic phase of the cardiac cycle was
      associated with dampened nociception.

PMID- 12236337
TI  - Confocal Raman microscopy for monitoring chemical reactions on single optically
      trapped, solid-phase support particles.
AB  - Optical trapping of small structures is a powerful tool for the manipulation and
      investigation of colloidal and particulate materials. The tight focus excitation
      requirements of optical trapping are well suited to confocal Raman microscopy. In
      this work, an inverted confocal Raman microscope is developed for studies of
      chemical reactions on single, optically trapped particles and applied to
      reactions used in solid-phase peptide synthesis. Optical trapping and levitation
      allow a particle to be moved away from the coverslip and into solution, avoiding
      fluorescence interference from the coverslip. More importantly, diffusion of
      reagents into the particle is not inhibited by a surface, so that reaction
      conditions mimic those of particles dispersed in solution. Optical trapping and
      levitation also maintain optical alignment, since the particle is centered
      laterally along the optical axis and within the focal plane of the objective,
      where both optical forces and light collection are maximized. Hour-long
      observations of chemical reactions on individual, trapped silica particles are
      reported. Using two-dimensional least-squares analysis methods, the Raman spectra
      collected during the course of a reaction can be resolved into component
      contributions. The resolved spectra of the time-varying species can be observed,
      as they bind to or cleave from the particle surface.

PMID- 12236338
TI  - DNA binding of an ethidium intercalator attached to a monolayer-protected gold
      cluster.
AB  - Ethidium intercalation has been investigated as a means of inducing binding of Au
      nanoparticles to DNA. The ethidium sites are attached to the nanoparticles as
      thiolate ligands, using 3,8-diamino-5-mercaptododecyl-6-phenylphenanthridinium
      (ethidium thiolate). Each nanoparticle bears only one or two ethidium thiolate
      ligands. The rest of the thiolate monolayer ligands on the monolayer-protected Au
      clusters (MPCs) were either N-(2-mercaptopropionyl)glycine (tiopronin/ethidium
      MPC) or trimethyl(mercaptoundecyl)ammonium (TMA/ethidium MPC). In solution
      mixtures of DNA and MPCs, the energy-transfer quenching of the ethidium ligands
      by the metal-like MPC core is partially released by ethidium binding to DNA, as
      observed by an increase in the intensity of ethidium fluorescence. Binding of the
      cationic TMA/ethidium MPC to DNA was efficient and rapid. The negatively charged
      tiopronin/ethidium MPC, in contrast, exhibits slow intercalation kinetics,
      relative to ethidium cation not attached to an MPC. The slow kinetics were
      analyzed as two competing binding interactions. The tiopronin/ethidium MPC
      binding to DNA was imaged by AFM.

PMID- 12236339
TI  - Multiplexed, high-throughput genotyping by single-base extension and end-labeled
      free-solution electrophoresis.
AB  - Technologies that allow for high-throughput, economical, and accurate single
      nucleotide polymorphism (SNP) genotyping are becoming crucial for modern genomic
      efforts. Here, we present a method for multiplexed single-base extension (SBE)
      genotyping that takes advantage of the unique separation modalities made possible
      via end-labeled free-solution electrophoresis (ELFSE). Three unique SBE
      oligonucleotide primers, which probe for mutations of clinical importance in the
      human p53 gene, were covalently conjugated to three unique polypeptoid frictional
      end labels and mixed together. This primer-polypeptoid conjugate cocktail was
      then used in a multiplexed SBE reaction followed by free-solution separation in a
      96-capillary array electrophoresis (CAE) instrument. The study was designed to
      demonstrate multiplexed SNP genotyping of several loci in a single reaction and a
      single subsequent analysis. Further, the electrophoretic analysis was conducted
      without any viscous polymeric separation media, was complete in less than 10 min,
      and can be implemented in any capillary or microfluidic electrophoretic system
      with four-color fluorescent detection capabilities. Multiplexed SBE-ELFSE
      genotyping analysis resulted in the simultaneous and accurate genotyping of three
      p53 loci on five different DNA templates in a single reaction set and single CAE
      analysis. With the implementation of this method in 96 or more capillaries in
      parallel, high-throughput screening of SNPs will be accessible to a large number
      of laboratories.

PMID- 12236340
TI  - Process analysis of recycled thermoplasts from consumer electronics by laser
      induced plasma spectroscopy.
AB  - An experimental setup for direct elemental analysis of recycled thermoplasts from
      consumer electronics by laser-induced plasma spectroscopy (LIPS, or laser-induced
      breakdown spectroscopy, LIBS) was realized. The combination of a echelle
      spectrograph, featuring a high resolution with a broad spectral coverage, with
      multivariate methods, such as PLS, PCR, and variable subset selection via a
      genetic algorithm, resulted in considerable improvements in selectivity and
      sensitivity for this complex matrix. With a normalization to carbon as internal
      standard, the limits of detection were in the ppm range. A preliminary pattern
      recognition study points to the possibility of polymer recognition via the line
      rich echelle spectra. Several experiments at an extruder within a recycling plant
      demonstrated successfully the capability of LIPS for different kinds of routine
      on-line process analysis.

PMID- 12236341
TI  - Rapid screening of aqueous chemical warfare agent degradation products: ambient
      pressure ion mobility mass spectrometry.
AB  - The use of electrospray ionization ambient pressure ion mobility spectrometry
      with an orthogonal reflector time-of-flight mass spectrometer to analyze chemical
      warfare (CW) degradation products from aqueous environmental samples has been
      demonstrated. Certified reference materials of analytical standards for the
      detection of Schedule 1, 2, or 3 toxic chemicals or their precursors as defined
      by the chemical warfare convention treaty verification were used in this study. A
      combination of six G/V-type nerve and four S-type vesicant related CW agent
      degradation products were separated with baseline resolution by this instrumental
      technique. Analytical figures of merit for each CW degradation product were
      determined. In some cases, reduced mobility constants (K0) have been reported for
      the first time. linear response ranges for the selected CW degradation products
      were found to be generally approximately 2 orders of magnitude, where the overall
      dynamic response ranges were found to extend to 4 orders of magnitude. Limits of
      detection for five of the nine chemical products tested were found to be less
      than 1 ppm. To demonstrate the potential of this instrumental method with complex
      mixtures, four CW degradation products were separated and detected from a spiked
      Palouse River water sample in less than 1 min. Finally, a homologous series of n
      alkylamines were used as baseline reference standards, producing a mobility/mass
      trend line to which the CW degradation products could be compared. Comparison of
      these products in this manner is expected to reduce the number of false
      positive/negative responses.

PMID- 12236342
TI  - Development of a multiplexed microcapillary liquid chromatography system for high
      throughput proteome analysis.
AB  - Comprehensive proteome analysis requires the identification (and quantification)
      of the proteins in samples consisting of thousands of proteins spanning a range
      of abundance of several orders of magnitude. The currency of proteome analysis by
      mass spectrometry is the peptides generated by protein proteolysis. The high
      sample complexity of such samples requires a large separation capacity, which is
      commonly achieved by fractionation of the mixture followed by further serial
      separations of each fraction. The sample throughput of proteome analysis is
      therefore limited by the need to sequentially process large numbers of samples.
      We have developed a novel four-plexed microcapillary liquid chromatography system
      for automated, high-throughput separation of complex peptide samples. The system
      supports the concurrent separation of four different samples by directing
      identically split solvent-gradient flows into four microcapillary C18 columns.
      The simple design of the system achieves multiplexed separation without the need
      for extra solvent pumps. Peak resolution, reproducibility, and parallel
      separating capacity of the system were investigated using standard peptides. The
      applicability of the system to high-throughput protein expression profiling was
      demonstrated in qualitative and quantitative analyses of protein expression in S.
      cerevisiae grown on two different carbon sources using the isotope-coded affinity
      tag (ICAT) reagent and matrix-assisted desorption/ionization quadrupole time-of
      flight mass spectrometry.

PMID- 12236343
TI  - Semiautomated analytical image correlation.
AB  - Machine vision refers to computer programs consisting of a collection of pattern
      recognition and digital image processing algorithms (Fabel, G. Motion Control
      2000, 53-54). A version of machine vision has been applied to correlating digital
      images generated by optical microscopy and secondary ion mass spectrometry
      (SIMS). By suitable application of image processing algorithms, semiautomated
      correlation between optical and secondary ion images is possible. For correlation
      of minor constituents evident in secondary ion images but invisible in optical
      images, correlation is performed by reference to the relative position of minor
      to major constituents. Precise coordinates of features apparent in one analytical
      image can be translated into the corresponding coordinates of an analytical image
      obtained by a different method. In principle, this capability yields a
      semiautomated system to combine complementary features of disparate imaging
      methods, such as secondary ion and optical microscopy.

PMID- 12236344
TI  - Screen printing of nucleic acid detecting carbon electrodes.
AB  - A large fraction of the presently mass-manufactured (> 10(8) units/year)
      electrochemical biosensors, used mostly by diabetic people to monitor their blood
      glucose levels, have screen-printed carbon working electrodes. An earlier study
      (Campbell, C. N., et al. Anal. Chem. 2002, 74, 158-162) showed that nucleic acids
      can be assayed at 1 nM concentrations by a sandwich-type amperometric method. The
      assay was performed with vitreous carbon working electrodes on which an electron
      conducting polycationic redox polymer and avidin were coelectrodeposited. Because
      the rate of the electrodeposition increases with the surface density of the
      polycationic redox polymer, its practicality depends on pretreatment of the
      surface, which adds anionic functions. (Gao, Z., et al. Angew. Chem. Int. Ed.
      2002, 41, 810-813). Here it is shown that the required conducting redox polymer
      films can be electrodeposited on potentially mass manufacturable electrodes made
      by screen-printing hydrophilic carbon inks on polyester sheets. The modified
      electrodes are made in two steps. First a polycationic electron-conducting redox
      polymer is cross-linked and electrodeposited by applying a negative potential.
      Next, an amine-terminated 20-base single-stranded oligonucleotide is
      electrodeposited by ligand-exchange. Both steps involve exchange of a labile
      inner sphere chloride ligand of the polymer-bound osmium-complex: Cross-linking
      and electrodeposition of the redox polymer result when inner-sphere chloride
      anions of the osmium complexes are exchanged by imidazole functions of
      neighboring chains. Incorporation of the oligonucleotide in the redox polymer
      results in the formation of a coordinative bond between the terminal amine
      (attached through a spacer to the oligonucleotide) and the osmium complex. In
      testing for the presence of a 38-base oligonucleotide, the analyte, in a 15- or
      25-microL droplet of hybridization solution, is hybridized with and captured by
      the 20-base electrode-bound sequence; then it is hybridized with an 18-base
      horseradish peroxidase labeled sequence. When the HRP label electrically contacts
      the redox polymer, the film becomes an electrocatalyst for the reduction of H2O2
      to water at 0.10 V (Ag/AgCl). Flow of the H2O2-reduction current indicates the
      presence of the assayed sequence.

PMID- 12236345
TI  - Recombinant Gaussia luciferase. Overexpression, purification, and analytical
      application of a bioluminescent reporter for DNA hybridization.
AB  - The cDNA for Gaussia luciferase (GLuc), the enzyme responsible for the
      bioluminescent reaction of the marine copepod Gaussia princeps, has been cloned
      recently. GLuc (MW = 19 900) catalyzes the oxidative decarboxylation of
      coelenterazine to produce coelenteramide and light. We report the first
      quantitative anaytical study of GLuc and examine its potential as a new reporter
      for DNA hybridization. A plasmid encoding both a biotin acceptor peptide-GLuc
      fusion protein as well as the enzyme biotin protein ligase (BPL) is engineered by
      using GLuc cDNA as a starting template. BPL catalyzes the covalent attachment of
      a single biotin to the fusion protein in vivo. Purification of GLuc is then
      accomplished by affinity chromatography using immobilized monomeric avidin.
      Moreover, the in vivo biotinylation enables subsequent complexation of GLuc with
      streptavidin (SA), thereby avoiding chemical conjugation reactions that are known
      to inactivate luciferases. Purified GLuc can be detected down to 1 amol with a
      signal-to-background ratio of 2 and a linear range extending over 5 orders of
      magnitude. The background luminescence of coelenterazine is the main limiting
      factor for even higher detectability of GLuc. Furthermore, the GLuc-SA complex is
      used as a detection reagent in a microtiter well-based DNA hybridization assay.
      The analytical range extends from 1.6 to 800 pmol/L of target DNA. Biotinylated
      GLuc produced from 1 L of bacterial culture is sufficient for 150,000
      hybridization assays.

PMID- 12236346
TI  - High-resolution solid-state CPMAS NMR study of archaeological woods.
AB  - High-resolution nuclear magnetic resonance of carbon-13 was employed to
      characterize archaeological wood samples from the 11th century excavation site in
      the lake Paladru at Charavines, France. Structural and chemical modifications
      were assessed by comparing the structural features of archaeological wood of
      beech with modern wood. The main results concern the strong decrease of a sugar
      moiety with a complete disappearance of hemicelluloses. During aging in a water
      environment, the beta-O-4 interunit linkages of lignins have not been degraded.
      The analysis of the NMR spectra reveals that the residues occurring during
      depletion of sugars were not recombined inside the lignocellulosic matrix.
      Finally, in this article we illustrate the possibility of analyzing small amounts
      (4-6 mg) of starting material within reasonable experimental time using modern
      equipment.

PMID- 12236347
TI  - Estrogen receptor binding assay method for endocrine disruptors using
      fluorescence polarization.
AB  - A rapid, simple and nonhazardous assay method for endcrine disruptors was
      developed using an estrogen receptor (ER) and fluorescence polarization (FP).
      Among the fluorescent compounds, the 17alpha-fluorescein-labeled estradiol
      derivative was selected as the most suitable ligand for the ER binding assay,
      since it showed the highest affinity to ER. In the Scatchard plot analysis, its
      convex curve exhibited a positive cooperative binding, indicating the induction
      of a conformational change of the ER with the binding of the ligand to form a
      dimer and to increase the affinity for the additional ligand. On the basis of the
      Hill plot analysis, its dissociation constant and Hill coefficient were 10.4 nM
      and 1.63, respectively. A competitive binding assay with an unlabeled 17beta
      estradiol (E2) yielded an IC50 value of 2.82 nM and a Hill coefficient of 1.67,
      thus providing a Ki value of 0.65 nM. In the same manner, the Hill coefficients
      for estrone, estriol, diethylstilbestrol, and tamoxifen were determined to be
      0.99, 1.17, 1.59, and 2.44, respectively.

PMID- 12236348
TI  - Ionization and fragmentation of humic substances in electrospray ionization
      Fourier transform-ion cyclotron resonance mass spectrometry.
AB  - Electrospray ionization (ESI) was combined with ultra-high-resolution Fourier
      transform-ion cyclotron resonance mass spectrometry (FTICR MS) to characterize
      complex humic and fulvic acid mixtures. Lower than expected molecular weight
      distributions previously observed for humics when analyzed by ESI-MS have fueled
      speculation about a bias in favor of low molecular weight. Multiply charged ions,
      ionization suppression, and sample fragmentation have all been suggested as
      sources of this low molecular weight bias. In this work, resolution of the
      individual components of humic mixtures within a 1 mass-to-charge unit window was
      accomplished by FTICR MS at 9.4 T. At mass resolving powers between 60,000 (high
      mass) and 120,000 (low mass), it was possible to determine that virtually all
      ions present in spectra of Suwannee River fulvic and humic acid are singly
      charged, thus eliminating inadequate accounting for multiply charged ions as a
      primary source of any low molecular weight bias. The high-resolution mass spectra
      also revealed the presence of molecular families containing ions that differ from
      each other in degree of saturation, functional group substitution (primarily CH
      vs N and CH4 vs O), and number of CH2 groups. Ionization suppression and ion
      fragmentation were addressed for humic and fulvic acid mixtures and well
      characterized poly(ethylene glycol) (PEG) mixtures with average molecular weights
      of 8000 and 10,000. Although these high molecular weight PEG mixtures fragment
      extensively under traditional positive-ion mode ESI conditions, similar
      fragmentation could not be confirmed for humic and fulvic acid mixtures.

PMID- 12236349
TI  - On-probe digestion of bacterial proteins for MALDI-MS.
AB  - On-probe digestion combined with MALDI mass spectrometry is studied as a rapid
      method for the analysis and identification of bacterial proteins. The use of
      trypsin adsorbed to the probe surface reduces the digestion time from hours to
      minutes. A high amount of trypsin must be applied to the probe for the successful
      digestion of bacterial proteins. Mass spectra of the digest contain a number of
      low-mass digest fragments. Several components of a B. subtilis bacterial digest
      can be identified through postsource decay and database searching.

PMID- 12236350
TI  - Identification of cross-linked peptides for protein interaction studies using
      mass spectrometry and 18O labeling.
AB  - A new method is presented to screen proteolytic mass maps of cross-linked protein
      complexes for the presence of cross-linked peptides and for the verification of
      proposed structures. On the basis of the incorporation of 18O from isotopically
      enriched water into the C-termini of proteolytic peptides, cross-linked peptides
      are readily distinguished in mass spectra by a characteristic 8 amu shift. This
      is due to the incorporation of two 18O atoms in each C-terminus, so that normal
      and surface-labeled peptides shift 4 amu and cross-linked peptides containing two
      C-termini will shift 8 amu compared with their unlabeled counterparts. The method
      is fast, sensitive, and reliable and can be combined with any available cross
      linking reagent and a wide range of proteolytic agents. As proof of principle, we
      successfully applied the method to a complex of two DNA repair proteins (Rad18
      Rad6) and identified the interaction domain.

PMID- 12236351
TI  - Metal complexation of thiacrown ether macrocycles by electrospray ionization mass
      spectrometry.
AB  - In the present study, electrospray ionization mass spectrometry is used to
      evaluate the metal-binding selectivities of an array of novel caged macrocycles
      for mercury(II), lead(II), cadmium(II), and zinc(II) ions. In homogeneous
      methanol/chloroform solutions as well as extractions of metals from aqueous
      solution by macrocycles in chloroform, it is found that the type of heteroatom
      (S, O, N), cavity size, and presence of other substituents influence the metal
      selectivities. Several of the macrocycles in this study bind mercury ion very
      selectively and efficiently in the presence of many other metal ions and have an
      avidity toward mercury that was tunable by the size and combination of
      heteroatoms in the macrocycle ring and the number of cage groups attached. The
      extraction mechanism was further investigated by determining the variation in
      extraction selectivity as a function of the counterions of the mercury salts.

PMID- 12236352
TI  - Optical detection and charge-state analysis of MALDI-generated particles with
      molecular masses larger than 5 MDa.
AB  - Charged polystyrene nanoparticles are generated by matrix-assisted laser
      desorption/ionization (MALDI) and detected by laser-induced fluorescence (LIF) in
      a quadrupole ion trap. Employing the LIF technique, observations of individual
      fluorescent nanospheres (27 nm in diameter and containing 180 fluorescein dye
      equivalents) have been achieved with an average signal-to-noise ratio of
      approximately 10. With the trap operating at a frequency around 5 kHz, charge
      state analysis of the particles reveals that the number of charges carried by the
      spheres is between 1 and 10. It suggests a mass-to-charge ratio (m/z) in the
      range of 10(5)-10(6) for the MALDI-generated particles. To effectively trap such
      large particles (m > 5 MDa), damping of the particles' motions by using
      approximately 50 mTorr He buffer gas is absolutely required. Similar findings are
      obtained for particles with a nominal size of 1 microm in diameter, demonstrating
      that production of charged particles with a molecular mass as high as 10(12) Da
      is possible using the MALDI technique.

PMID- 12236353
TI  - Modulator design for comprehensive two-dimensional gas chromatography:
      quantitative analysis of polyaromatic hydrocarbons and polychlorinated biphenyls.
AB  - A novel cryogenic modulator was constructed for comprehensive two-dimensional gas
      chromatography (GC x GC). The modulator is based on two-step cryogenic trapping
      with CO2 and thermal desorption with electric heating. The GC x GC system
      included a nonpolar first-dimension column and two semipolar second-dimension
      columns, one connected to a flame ionization detector and the other one to a
      electron capture detector. A Matlab-based program, which allowed determination of
      peak heights and volumes, was written for the data analysis. The GC x GC system
      was applied for the analysis of polyaromatic hydrocarbons and polychlorinated
      biphenyls. The functioning of the modulator and the quantitativity of the method
      were studied with both peak volumes and peak heights from a three-dimensional
      plot. The separate peak areas from the modulated chromatogram were calculated as
      a comparison. The quantitative results were compared with those obtained with the
      same system but without the thermal modulation. The method was found to be
      repeatable and linear with use of peak volumes as well as peak heights. There was
      also good agreement with the results obtained by integration of separate peak
      areas. The developed GC x GC method was applied to the analysis of a Soxhlet
      extract of a certified sediment sample. The results were compared with the
      certified values.

PMID- 12236354
TI  - Solute-solvent interactions in micellar electrokinetic chromatography. 6.
      Optimization of the selectivity of lithium dodecyl sulfate-lithium
      perfluorooctanesulfonate mixed micellar buffers.
AB  - The optimization of the composition of mixed surfactants used as micellar
      electrokinetic chromatography (MEKC) pseudostationary phases is proposed as an
      effective method for the separation of complex mixtures of analytes. The
      solvation parameter model is used to select two surfactants (lithium dodecyl
      sulfate, LDS, and lithium perfluorooctanesulfonate, LPFOS) with contrasting
      solvation properties. Combination of these two surfactants allows variations of
      the solvation properties of MEKC pseudostationary phase along a wide range. Thus,
      the convenient variation of the proportion of both surfactants allows an
      effective control of the selectivity in such systems. An algorithm that predicts
      the overall resolution of a given mixture of compounds is described and applied
      to optimize the composition of the mixed surfactant for the separation of the
      mixture. The algorithm is based on the calculation of peak purities on simulated
      chromatograms as a function of the composition of the mixed LDS/LPFOS micellar
      buffer from data at several micellar buffer compositions. Successful separations
      were achieved for mixtures containing up to 20 compounds, in less than 12 min.

PMID- 12236355
TI  - Equilibrium gradient methods with nonlinear field intensity gradient: a
      theoretical approach.
AB  - Equilibrium gradient methods belong to a family of separation techniques in which
      analytes are forced to unique equilibrium points by a force gradient and a
      counter force along the separation pathway. The basic theory for equilibrium
      gradient methods where the force gradient is induced by a field gradient is
      developed in this paper. The results indicate that peak capacity can be
      dynamically improved by using a nonlinear field-intensity gradient in which the
      first section is steep, and the following section is shallow. Using
      electromobility focusing (EMF) as an example, a separation model is established.
      EMF is an equilibrium gradient method that uses an electric field intensity
      gradient to induce a force gradient on charged analytes, such as proteins, and a
      constant hydrodynamic flow as an opposing force. Equations relating operating
      parameters with separation performance are given. Although simulation results
      show that a peak capacity of over 10,000 is theoretically possible using a single
      channel in a separation time just under 2 months, if 100 parallel separation
      units are utilized in an array format under the same operating conditions, the
      same peak capacity can be obtained in just over 12 h.

PMID- 12236356
TI  - Student knowledge: who owns it?

PMID- 12236357
TI  - High-resolution capillary tube NMR. A miniaturized 5-microL high-sensitivity TXI
      probe for mass-limited samples, off-line LC NMR, and HT NMR.
AB  - A new triple-resonance (TXI) (1H, 13C, 15N) high-resolution nuclear magnetic
      resonance (NMR) capillary probe with 2.5-microL NMR-active sample volume (V(obs))
      was built and tested for applications with mass- and volume-limited samples and
      for coupling of microbore liquid chromatography to NMR. This is the first
      microliter probe with optimized coil geometry for use with individual capillary
      tubes with an outer diameter of 1 mm. The 90 degree pulse lengths of the 1-mm
      microliter probe were below 2 micros for proton, below 8 micros for carbon, and
      below 20 micros for nitrogen, and a spectral line width at signal half-height
      below 1 Hz was obtained. Compared to a conventional 5-mm probe, the new 600-MHz 1
      mm TXI microliter probe with z-gradient shows an increase in mass sensitivity by
      a factor of 5, corresponding to a 25-fold reduction in measuring time. The
      consumption of costly deuterated solvent is reduced by at least 2 orders of
      magnitude. The 1-mm TXI microliter probe with z-gradient allows the measurement
      of one-dimensional 1H NMR and two-dimensional heteronuclear NMR spectra with a
      few nanomoles (micrograms) of compound with high sensitivity, speed, and quality.
      This is a breakthrough for discrete sample NMR spectroscopy with paramount
      importance for structure elucidation in natural compound chemistry and metabolic
      research. It offers also advantages for linking chromatographic methods to NMR in
      a nindustrial environment. Capillary tube NMR may find new applications in areas
      where high sample throughput is essential, e.g., in the quality control of large
      sample arrays from parallel chemistry, screening, and compound depositories. It
      has the potential to increase the sample throughput by 1 order of magnitude or
      more if new hardware for fast sample handling and exchange becomes available.

PMID- 12236358
TI  - Spatial two-photon fluorescence cross-correlation spectroscopy for controlling
      molecular transport in microfluidic structures.
AB  - The increasing availability of microfluidic systems of various geometries and
      materials for the downscaling of chemical or biochemical processes raises a
      strong demand for adequate techniques to precisely determine flow parameters and
      to control fluid and particle manipulation. Of all readout parameters,
      fluorescence analysis of the fluid or suspended particles is particularly
      attractive, as it can be employed without mechanical interference and with a
      sensitivity high enough to detect single molecules in aqueous environments. In
      this study, we present the determination of flow parameters, such as velocity and
      direction, in microstructured channels by fluorescence correlation spectroscopy
      (FCS), a method based on single molecule spectroscopy carried out in confocal
      optical setups. Different modes of FCS, such as auto- and dual-beam cross
      correlation techniques by one- and two-photon excitation, are discussed. Known
      advantages of two-photon excitation, such as highly restricted detection volumes
      and low scattering background, are shown to be particularly valuable for
      measurements in tiny channel systems. Although conventional autocorrelation is
      sufficient for describing the velocity of single molecules, dual-beam cross
      correlation allows the separation of isotropic and anisotropic dynamics, for
      example, to monitor flow directions or to discriminate against photophysical
      effects that could be mistaken for mobility parameters. It can be shown that time
      gated two-photon excitation in the dual-beam mode significantly lowers the
      undesired cross-talk between the two measurement volumes. Finally, some
      applications, such as the calibration of microfluidic sorting units and flow
      profiling, are demonstrated.

PMID- 12236359
TI  - Near-field thermal lens detection at 257 nm as an alternative to absorption
      spectrometric detection in combination with electromigrative separation
      techniques.
AB  - A device is presented that permits detection of analytes absorbing
      electromagnetic radiation at lambda = 257 nm (in fused-silica capillaries with 75
      microm i.d.) via the near-field thermal lens effect. The detector was realized by
      using a frequency-doubled argon ion laser as pump laser and a laser diode
      (emission wavelength, 633 nm) coupled into a monomode optical fiber as probe
      laser. Comparing the performance of this detector to the performance of a
      commercial absorption spectrometric detector working at lambda = 257 nm equipped
      with a unit for on-column detection in fused-silica capillaries showed a
      substantial improvement in detection limits (up to 30-fold improvement) for the
      near-field thermal lens detector (NF-TLD). The feasibility of the NF-TLD for
      sensitive detection of nonfluorescent analytes in real samples after separation
      by micellar electrokinetic chromatography was shown taking the determination of
      nitroaromatic compounds in contaminated water from a former ammunition plant as
      an example. Dependence of the thermal lens signal on pump laser power, velocity
      of the mobile phase, and chopper frequency was investigated. A linear calibration
      range over 2 orders of magnitude was obtained.

PMID- 12236361
TI  - Steric-hyperlayer sedimentation field flow fractionation and flow cytometry
      analysis applied to the study of Saccharomyces cerevisiae.
AB  - Sedimentation field flow fractionation separation associated with flow cytometry
      has been used for the characterization of several commercial Saccharomyces
      cerevisiae yeasts used for wine production. A new type of channel 80 microm thick
      and new operating conditions, such as sample introduction when field and flow are
      established and a channel inlet connected to the accumulation wall, were used.
      Good repeatability (5% RSD) and reduced analysis time (2-10 min) were obtained.
      The avoidance of the stop-flow relaxation process in conjunction with the use of
      a channel of reduced thickness has demonstrated that an effective "steric
      hyperlayer" mode driving to a major focusing effect of the species in the channel
      thickness is involved in the elution of the yeast cells. Flow cytometry analyses
      were performed, and the forward scattering and side scattering yeast
      characteristics correlation maps were obtained. Field flow fractionation and flow
      cytometry information obtained indicated that the fractogram profiles of the
      yeast cell depended not only on the size, but also on the shape and density.

PMID- 12236360
TI  - An aptamer-based quartz crystal protein biosensor.
AB  - We developed a quartz crystal biosensor designed to detect concentrations and
      ligand affinity parameters of free unlabeled proteins in real time. Using a model
      system with human IgE as the analyte and single-stranded DNA aptamers or an anti
      IgE antibody as immobilized ligands, we could demonstrate that aptamers were
      equivalent to antibodies in terms of specificity and sensitivity. Both receptor
      types selectively detected 0.5 nmol/L of IgE. In addition, the aptamer receptors
      tolerated repeated affine layer regeneration after ligand binding and recycling
      of the biosensor with little loss of sensitivity. Because of the small size and
      nonprotein nature of the aptamers, they were immobilized in a dense, well
      oriented manner, thus extending the linear detection range to 10-fold higher
      concentrations of IgE. In addition to demonstrating for the first time that an
      aptamer-based biosensor can specifically and quantitatively detect an analyte in
      various complex protein mixes, the aptamer-ligand proved to be relatively heat
      resistant and stable over several weeks. Since aptamers consist of nucleic acids,
      well-established chemistry can be applied to produce optimized affine layers on
      biosensors that may be developed to specifically detect proteins in solution for
      analysis of proteomes.

PMID- 12236362
TI  - ESI-MS/MS for the differentiation of diastereomeric pyrimidine glycols in
      mononucleosides.
AB  - Pyrimidine glycols, or 5,6-dihydroxy-5,6-dihydropyrimidines, are primary lesions
      in DNA induced by reactive oxygen species. In this article, we report the
      preparation and tandem mass spectrometry (MS/MS) characterization of the two cis
      diastereomers of the glycol lesions of 2'-deoxyuridine, 5-methyl-2'
      deoxycytidine, and thymidine. Our results show that collisional activation of the
      [M + Na]+ ions of all the three pairs of cis isomers and that of the [M + H]+
      ions of the 2'-deoxyuridine glycols and 5-methyl-2'-deoxycytidine glycols give a
      facile loss of a water molecule. Interestingly, the water loss occurs more
      readily for the 6S isomer than for the 6R isomer. Likewise, product ion spectra
      of the [M - H]- ions of the two cis isomers of the 2'-deoxyuridine glycols and
      thymidine glycols show more facile loss of water for the 6S isomer than for the
      6R isomer. MS/MS acquired at different collisional energies gave similar results,
      which establishes the reproducibility of spectra.

PMID- 12236363
TI  - Potential application of gas chromatography/tandem mass spectrometry in the
      measurement of coeluting isomers.
AB  - Despite the unprecedented popularity of separation chromatography, the
      measurement of coeluting isomeric chemicals remains an extremely difficult task.
      We developed an analytical scheme capable of measuring two coeluting isomers
      using a single chromatographic column and a gas chromatography/tandem mass
      spectrometry system. The protocol utilized two product ion fragments generated
      from a common parent ion associated with the isomers for quantitation. The
      utility of the analytical scheme was demonstrated with the measurements of
      several pairs of coeluting polychlorinated biphenyl (PCB) isomers in standard
      solutions and fish liver samples. Best results were given when a set of stringent
      constraints for the abundance ratio of the two product ion fragments was
      satisfied. Analyses of seven fish liver samples collected from nearshore San
      Diego, CA, indicated that the domain that had been previously reported to
      comprise PCB 153 and PCB 168 actually contained PCB 153 only. Although only a
      selected number of PCB congeners were examined, the results presented indicate
      that the analytical scheme has the potential to be used to determine the
      concentrations of all chromatographically coeluted isomers.

PMID- 12236364
TI  - A method to evaluate the renin-angiotensin system in rat renal cortex using a
      microdialysis technique combined with HPLC-fluorescence detection.
AB  - A microdialysis (MD) technique, combined with HPLC-fluorescence (FL) detection,
      was developed for the evaluation of the tissue-specific renin-angiotensin system
      (RAS) in the rat renal cortex. An MD probe constructed with a hydrophilic hollow
      fiber dialysis tubing, AN69, showed high recovery (more than 50%) in vitro for
      all four angiotensins: angiotensin I (Ang I), Ang II, Ang III, and Ang (1-7).
      Angiotensins, successfully derivatized with m-BS-ABD-F, a water-soluble
      fluorogenic reagent that has a 2,1,3-benzoxadiazole (benzofurazan) structure,
      could be simultaneously determined by coupled-column HPLC. The detection limit
      for Ang I, Ang II, Ang III, and Ang (1-7) were 94, 44, 47, and 83 fmol,
      respectively. All these peptides were determined with good linearity (0.0125-3.1
      microM, equivalent to 0.25-62 pmol, correlation coefficient >0.99) and good
      precision (recovery >91%). In the MD studies, generation of Ang (1-7) and Ang II
      was observed when Ang I was perfused, and Ang (1-7) was the major biologically
      active angiotensin found in the dialysate samples. The concentration of Ang (1-7)
      and Ang II in the dialysate samples showed good correlation to that of Ang I in a
      MD perfusate (20-100 microM). Cleavage of Ang I to Ang (1-7) was drastically
      suppressed by the co-perfusion of phoshoramidon (0.5-5 mM), an inhibitor of
      neprilysin, which generates Ang (1-7) from Ang I. These results are consistent
      with the previously reported characteristics of tissue-specific renal RAS,
      suggesting that our MD/HPLC-FL system may have the potential to be employed to
      evaluate tissue-specific RAS in the rat renal cortex.

PMID- 12236365
TI  - A method to assess genomic DNA methylation using high-performance liquid
      chromatography/electrospray ionization mass spectrometry.
AB  - Eukaryotic DNA is methylated at some cytosine residues, and this epigenetic
      feature performs critical functions. We developed a method for quantitative
      determination of 5-methyl-2'-deoxycytidine in human DNA using liquid
      chromatography/electrospray ionization mass spectrometry (LC/ESI-MS). The DNA was
      enzymatically hydrolyzed by sequential digestion with three enzymes. DNA
      hydrolyzates were subsequently separated by reversed-phase high-performance
      liquid chromatography in isocratic mode. The four major DNA bases and 5-methyl-2'
      deoxycytidine were resolved and eluted in 13 min. Identification of 2'
      deoxycytidine and 5-methyl-2'-deoxycytidine was obtained by combined diode array
      UV spectra analysis and mass spectra of chromatographic peaks. The isotopomers
      [15N3]-2'-deoxycytidine and (methyl-d3,ring-6-d1)-5-methyl-2'-deoxycytidine were
      used as internal standards. Ions of m/z 126 and 130 were used to detect 5-methyl
      2'-deoxycytidine and its isotopomer, and ions of m/z 112 and 115 were used to
      detect 2'-deoxycytidine and its stable isotopomer, respectively. The DNA
      methylation status was calculated on the basis of the amount of 5-methyl-2'
      deoxycytidine per microgram of DNA with percent relative standard deviations
      (%RSD) for a method precision of 7.1 (within-day) and 5.7 (day-to-day). This
      method also allows the measurement of 5-methyl-2'-deoxycytidine expressed as a
      percentage of total deoxycytidine residues in genomic DNA with %RSD for method
      precision of 1.9 (within-day) and 1.7 (day-to-day). This LC/MS method for
      quantitative determination of genomic DNA methylation status is rapid, sensitive,
      selective, and precise.

PMID- 12236366
TI  - Wavelength-dispersive total-reflection X-ray fluorescence with an efficient
      Johansson spectrometer and an undulator X-ray source: detection of 10-16 g-level
      trace metals.
AB  - The present paper reports significant enhancement of the detection power for
      total-reflection X-ray fluorescence (TXRF). The employment of an efficient
      wavelength-dispersive spectrometer rather than a conventional Si(Li) detector, as
      well as the use of a quasi-monochromatic undulator X-ray source, completely
      changed the quality of X-ray florescence spectra. The energy resolution is 20
      times better, which effectively contributes to reducing the low-energy tail of
      the scattering background and to separating neighboring X-ray florescence peaks.
      Another advantage is its capability with respect to high-counting-rate
      measurements, which ensure the detection of weak signals from trace materials.
      The absolute and relative detection limit for nickel are 3.1 x 10(-16) g and 3.1
      ppt (pg/g) for a 0.1-microL droplet of pure water, respectively, which is nearly
      50 times better than the current best data achieved by conventional energy
      dispersive TXRF using a Si(Li) detector system.

PMID- 12236367
TI  - Anomalous radial migration of single DNA molecules in capillary electrophoresis.
AB  - We report the unexpected radial migration of DNA molecules in capillary
      electrophoresis (CE) with applied Poiseuille flow. Such movement can contribute
      to anomalous migration times, peak dispersion, and size and shape selectivity in
      CE. When Poiseuille flow is applied from the cathode to the anode, DNA molecules
      move toward the center of the capillary, forming a narrow, highly concentrated
      zone. Conversely, when the flow is applied from the anode to the cathode, DNA
      molecules move toward the walls, leaving a DNA-depleted zone around the axis. We
      showed that the deformation and orientation of DNA molecules under Poiseuille
      flow was responsible for the radial migration. By analyzing the forces acting on
      the deformed and oriented DNA molecules, we derived an expression for the radial
      lift force, which explained our results very well under different conditions with
      Poiseuille flow only, electrophoresis only, and the combination of Poiseuille
      flow and electrophoresis. Factors governing the direction and velocity of radial
      migration were elucidated. Potential applications of this phenomenon include an
      alternative to sheath flow in flow cytometry, improving precision and reliability
      of single-molecule detection, reduction of wall adsorption, and size separation
      with a mechanism akin to field-flow fractionation. On the negative side,
      nonuniform electroosmotic flow along the capillary or microfluidic channel is
      common in CE, and radial migration of certain analytes cannot be neglected.

PMID- 12236368
TI  - Optical chloride sensor based on dimer-monomer equilibrium of indium(III)
      octaethylporphyrin in polymeric film.
AB  - A novel transduction chemistry for preparing optical anion-selective polymeric
      films that respond reversibly and selectively to chloride ion activity is
      demonstrated. The chloride sensors are prepared by casting thin (5-10 microm)
      plasticized PVC films containing indium(III) octaethylporphyrin hydroxide, along
      with optimized levels of a lipophilic tetraphenylborate salt, onto glass slides.
      When bathed in low-pH buffered solutions void of chloride, the porphyrin species
      spontaneously forms a hydroxide ion-bridged dimer, with the added lipophilic
      borate species serving as the counteranion for this complex. The maximum for the
      Soret absorption band of this dimeric species is shifted to 390 nm, from 410 nm
      for the initial monomeric porphyrin. Increases in chloride ion levels in the
      bathing solution results in chloride extraction and ligation to the In(III)
      center, and concomitant breaking of the dimer into monomeric porphyrin species,
      yielding a decrease in absorbance at 390 nm and an increase in optical signal at
      410 nm. Under optimized conditions, optical selectivity coefficients toward
      chloride over a wide range of other anions (NO3-, ClO4-, SCN-, SO4(2-), F-, Br-,
      H2PO4-) are measured to be < 10(-3). Of all anions tested, only salicylate yields
      a slightly greater response than chloride. This selectivity is shown to be
      adequate for reversible and accurate sensing of chloride levels in diluted serum
      samples.

PMID- 12236369
TI  - A microscale-molecular weight sensor: probing molecular diffusion between
      adjacent laminar flows by refractive index gradient detection.
AB  - A detection scheme that measures the refractive index gradient (RIG) between
      adjacent laminar flows in a microfluidic device has been used to develop a
      microscale-molecular weight sensor. The behavior of low Reynolds number flows has
      been well documented and shows that molecular transport (mixing) between adjacent
      laminar flows occurs by molecular diffusion between flow boundaries. A diode
      laser beam, incident upon and illuminating the entire width of a microchannel,
      measured the transverse concentration gradient at two different positions along a
      microchannel. The concentration gradient is impacted by the transverse diffusion
      from a flow with analyte into a flow initially without analyte. The RIG that
      forms as analyte diffuses from one adjacent flow to the other causes the laser
      beam, impinging orthogonal to the RIG through the microchannel, to be deflected.
      The angle of deflection is then monitored on a position-sensitive detector (PSD)
      at two different positions along the axis of flow to provide a measurement of
      analyte diffusion. The two positions are just after the flow initially without
      analyte merges with the flow initially containing all of the analyte (upstream)
      and then after the two streams have had more time to diffuse together
      (downstream). The ratio of the PSD signals obtained at the two positions along
      the flow, downstream signal divided by the upstream signal, is readily correlated
      to the analyte diffusion coefficient and, thus, the analyte molecular weight for
      a given class of compounds. The device was evaluated as a molecular weight sensor
      for poly(ethylene glycol) (PEG) solutions over a molar mass range from 106 to
      22,800 g/mol. The ratio signal was found to be both independent of PEG
      concentration and sensitive to molecular weight changes for samples ranging from
      960 to 22,800 g/mol. Independence of concentration is important for obtaining a
      reliable molecular weight measurement. The limit of detection for 11,840 g/mol
      PEG measured at the upstream detection position was determined to be 56 ppm,
      equivalent to 4.5 x 10(-6) RI (3sigma). This technique provides a much needed
      universal detection method, without requiring analyte derivatization chemistry
      (e.g., fluorescence), for microfluidic analyses that are becoming increasingly
      useful in monitoring chemical systems such as continuous-flow reactors or batch
      polymerization processes. Thus, the molecular weight determination capability is
      potentially applicable to other compound classes, such as DNA or proteins.

PMID- 12236370
TI  - Fabrication of microchannel structures in fluorinated ethylene propylene.
AB  - A new technique for fabrication of channel structures with diameters down to 13
      microm in fluorinated ethylene propylene (also known as poly(tetrafluoroethylene
      co-hexafluoropropylene), FEP) is described. The technique is based on the unique
      property of a dual-layer fluoropolymer tubing consisting of an outer layer of
      poly(tetrafluoroethylene) (PTFE) and an inner layer of FEP. When heated (>350
      degrees C), the outer PTFE layer shrinks while the inner FEP layer melts,
      resulting in filling of all empty space inside the tubing with FEP. The channel
      structures are formed using tungsten wires as templates that are pulled out after
      completion of the shrinking and melting process. While several analytical devices
      have been reproducibly prepared and shown to function, this report describes a
      single example. A microreactor coupled to an electrochemical flow cell detects
      the biuret complex of the natively electroinactive peptide des-Tyr-Leu
      enkephalin.

PMID- 12236371
TI  - Analysis of biomolecular interactions using a miniaturized surface plasmon
      resonance sensor.
AB  - A commercially available miniaturized surface plasmon resonance sensor has been
      investigated for its applicability to biological interaction analysis. The sensor
      was found to exhibit excellent repeatability and linearity for high-refractive
      index solutions and good reproducibility for the binding of proteins. Its
      detection limit for the monoclonal antibody M1 was found to be 2.1 fmol, which
      corresponds to a surface concentration of 21 pg/mm2. Simple surface
      immobilization procedures relying on biotin/avidin or glycoprotein/lectin
      chemistry have been explored. Equilibrium dissociation constants for the binding
      of the FLAG peptide to its monoclonal antibody (M1) and for the binding of
      concanavalin A to a glycoprotein have been determined. The close agreement of
      these measurements with values obtained by surface fluorescence microscopy and
      fluorescence correlation spectroscopy helps to validate the use of this device.
      Thus, this sensor shows promise as an inexpensive, portable, and accurate tool
      for bioanalytical applications in laboratory and clinical settings.

PMID- 12236372
TI  - Diffusive-convective transport into a porous membrane. A comparison of theory and
      experiment using scanning electrochemical microscopy operated in reverse imaging
      mode.
AB  - Molecule transfer at the interface between a single ion-selective micropore and
      aqueous solutions is quantitatively investigated using scanning electrochemical
      microscopy operated in reverse imaging mode (SECM-RIM). Accumulation of two
      electroactive solute molecules, acetaminophen and
      ferrocenylmethyltrimethylammonium, at the pore/solution interface is observed
      when an electrical current is passed through the pore. Slow interfacial transfer
      of solute relative to the solvent as the solution is driven across the membrane
      by electroosmosis is responsible for solute accumulation. A theoretical
      expression for the concentration distribution of solute molecules above an
      individual pore opening is obtained by analytical solution of the convective
      diffusive flux equation. The fluid velocity through the pore at constant
      electroosmotic force is determined by fitting the theoretical expression to SECM
      RIM concentration profiles and is found, as anticipated, to be independent of the
      solute species and the bulk solute concentration. The results provide a
      theoretical basis for the SECM-RIM imaging of biological membranes as well as a
      general method for characterizing interfacial molecule/ion transfer kinetics.

PMID- 12236373
TI  - On-line temperature monitoring in a capillary electrochromatography frit using
      microcoil NMR.
AB  - A new nuclear magnetic resonance (NMR) spectroscopy probe has been designed to
      measure the temperature of the water inside a capillary. The probe provides the
      ability to measure the temperature in a several hundred micrometer long capillary
      section, corresponding to liquid volumes in the picoliter to nanoliter range with
      a temperature monitoring accuracy of 0.2 degrees C. The NMR probe is based on a
      novel two-turn vertical solenoidal design, and its performance for capillary
      scale temperature measurements is characterized. The temperature rise in a
      chromatographic frit of the type used in capillary electrochromatography is
      measured as a function of applied power, and temperature rises of more than 50
      degrees C are observed. The temperature of the electrolyte cools rapidly after
      exiting the frit and can be followed as a function of distance from the frit. The
      ability to accurately monitor the temperature of water as it moves through porous
      materials such as packed chromatographic beds and frits is important to allow the
      effects of temperature on CEC separation performance to be determined.

PMID- 12236374
TI  - Cryogenic probe 13C NMR spectroscopy of urine for metabonomic studies.
AB  - Cryogenic probe technology can significantly compensate for the inherently low
      sensitivity of natural abundance 13C NMR spectroscopy. This now permits its
      routine use in NMR spectroscopy of biofluids, such as urine or plasma, with
      acquisition times that enable a high throughput of samples. Metabonomic studies
      often generate numerous samples in order to characterize fully the time-dependent
      biochemical response to stimuli, but until now, they have been largely conducted
      using 1H NMR spectroscopy because of its high sensitivity and hence efficient
      data acquisition. Here, we demonstrate that information-rich 13C NMR spectra of
      rat urine can be obtained using appropriately short acquisition times suitable
      for biochemical samples when using a cryogenic probe. Furthermore, these data
      were amenable to automated pattern recognition analysis, which produced a profile
      of the metabolic response to the model hepatotoxin hydrazine that was consistent
      with earlier studies. Thus, a new source of detailed and complementary
      information is available to metabonomics using cryogenic probe 13C NMR
      spectroscopy.

PMID- 12236375
TI  - Dynamic array cytometer: grabbing the bull by the horns.

PMID- 12236376
TI  - Analytical chemistry at the forefront of homeland defense.

PMID- 12236377
TI  - Atmospheric pressure MALDI.

PMID- 12236378
TI  - Mapping the world of analytical chemistry.

PMID- 12236379
TI  - Analyzing a comet nucleus by capillary GC.

PMID- 12236380
TI  - Ion traps come of age.

PMID- 12236382
TI  - Understanding coordination of care from the consumer's perspective in a regional
      health system.
AB  - OBJECTIVE: To understand and develop a model about the meaning of coordination to
      consumers who experienced a transition from acute care to home care. STUDY
      DESIGN: A qualitative, exploratory study using Grounded Theory. DATA
      SOURCES/ANALYSIS: Thirty-three consumers in the Calgary Regional Health Authority
      who had experienced the transition from an acute care hospital back into the
      community with home care support were interviewed. They were asked to describe
      their transition experience and what aspects of coordination were important to
      them. Interviews were recorded, transcribed, and analyzed using constant
      comparison. The coding and retrieval of information was facilitated by the
      computer software program Nud*ist. PRINCIPAL FINDINGS: The resulting model has
      four components: (1) the meaning of coordination to consumers; (2) aspects of
      health care system support that are important for coordination; (3) elements that
      prepared consumers to return home; and (4) the components of a successful
      transition experience. Consumers appeared to play a crucial role in spanning
      organizational boundaries by participating in the coordination of their own care.
      CONCLUSIONS: Consumers must be included in health care decisions as recipients of
      services and major players in the transition processes related to their care.
      Health care providers need to ensure that consumers are prepared to carry out
      their coordination role and managers need to foster a culture that values the
      consumer "voice" in organizational processes.

PMID- 12236381
TI  - Understanding team-based quality improvement for depression in primary care.
AB  - OBJECTIVE: To assess the impacts of the characteristics of quality improvement
      (QI) teams and their environments on team success in designing and implementing
      high quality, enduring depression care improvement programs in primary care (PC)
      practices. STUDY SETTING/DATA SOURCES: Two nonprofit managed care organizations
      sponsored five QI teams tasked with improving care for depression in large PC
      practices. Data on characteristics of the teams and their environments is from
      observer process notes, national expert ratings, administrative data, and
      interviews. STUDY DESIGN: Comparative formative evaluation of the quality and
      duration of implementation of the depression improvement programs developed by
      Central Teams (CTs) emphasizing expert design and Local Teams (LTs) emphasizing
      participatory local clinician design, and of the effects of additional team and
      environmental factors on each type of team. Both types of teams depended upon
      local clinicians for implementation. PRINCIPAL FINDINGS: The CT intervention
      program designs were more evidence-based than those of LTs. Expert team
      leadership, support from local practice management, and support from local mental
      health specialists strongly influenced the development of successful team
      programs. The CTs and LTs were equally successful when these conditions could be
      met, but CTs were more successful than LTs in less supportive environments.
      CONCLUSIONS: The LT approach to QI for depression requires high local support and
      expertise from primary care and mental health clinicians. The CT approach is more
      likely to succeed than the LT approach when local practice conditions are not
      optimal.

PMID- 12236383
TI  - Alcohol, drug abuse, and mental health care for uninsured and insured adults.
AB  - OBJECTIVE: To compare adults with different insurance coverage in care for
      alcohol, drug abuse, and mental health (ADM) problems. DATA SOURCES/STUDY
      SETTING: From a national telephone survey of 9,585 respondents. DESIGN: Follow-up
      of adult participants in the Community Tracking Study. DATA COLLECTION: Self
      report survey of insurance plan (Medicare, Medicaid, unmanaged, fully, or
      partially managed private, or uninsured), ADM need, use of ADM services and
      treatments, and satisfaction with care in the last 12 months. PRINCIPAL METHODS:
      Logistic and linear regressions were used to compare persons by insurance type in
      ADM use. PRINCIPAL FINDINGS: The likelihood of ADM care was highest under
      Medicaid and lowest for the uninsured and those under Medicare. Perceived unmet
      need was highest for the uninsured and lowest under Medicare. Persons in fully
      rather than partially managed private plans tend to be more likely to have ADM
      care and ADM treatments given need. Satisfaction with care was high in public
      plans and low for the uninsured. CONCLUSIONS: The uninsured have the most
      problems with access to and quality of ADM care, relative to the somewhat
      comparable Medicaid population. Persons in fully managed plans had better rather
      than worse access and quality compared to partially managed plans, but findings
      are exploratory. Despite low ADM use, those with Medicare tend to be satisfied.
      Across plans, unmet need for ADM care was high, suggesting changes are needed in
      policy and practice.

PMID- 12236384
TI  - Issues in conducting randomized controlled trials of health services research
      interventions in nonacademic practice settings: the case of retail pharmacies.
AB  - OBJECTIVE: To describe unexpected challenges and strategies to overcome them when
      conducting randomized controlled trials (RCT) of health services research
      interventions in retail pharmacies. STUDY SETTING: Thirty-six retail drug stores
      in Indianapolis. STUDY DESIGN: We conducted an RCT to evaluate the effectiveness
      of an intervention to increase pharmacists' involvement in caring for customers.
      We describe: (1) our RCT as originally designed, (2) unexpected challenges we
      faced; and (3) how we resolved those challenges. DATA COLLECTION/EXTRACTION
      METHODS: Randomized controlled trial. PRINCIPAL FINDINGS: Major modifications in
      research design were necessitated by factors such as corporate restructuring,
      heightened sensitivity to patient confidentiality, and difficulties altering
      employees' behavior. We overcame these barriers by conducting research that is
      consistent with corporate goals, involving appropriate corporate administrators
      and technical personnel early in the process, and being flexible. CONCLUSIONS:
      Health services researchers should conduct RCTs in a variety of non-academic
      practice settings to increase generalizability and better reflect the true impact
      of interventions. Pragmatic problems, although significant, can be successfully
      overcome.

PMID- 12236385
TI  - Diagnostic cost groups (DCGs) and concurrent utilization among patients with
      substance abuse disorders.
AB  - OBJECTIVE: To assess the performance of Diagnostic Cost Groups (DCGs) in
      explaining variation in concurrent utilization for a defined subgroup, patients
      with substance abuse (SA) disorders, within the Department of Veterans Affairs
      (VA). DATA SOURCES: A 60 percent random sample of veterans who used health care
      services during Fiscal Year (FY) 1997 was obtained from VA administrative
      databases. Patients with SA disorders (13.3 percent) were identified from primary
      and secondary ICD-9-CM diagnosis codes. STUDY DESIGN: Concurrent risk adjustment
      models were fitted and tested using the DCG/HCC model. Three outcome measures
      were defined: (1) "service days" (the sum of a patient's inpatient and outpatient
      visit days), (2) mental health/substance abuse (MH/SA) service days, and (3)
      ambulatory provider encounters. To improve model performance, we ran three
      DCG/HCC models with additional indicators for patients with SA disorders. DATA
      COLLECTION: To create a single file of veterans who used health care services in
      FY 1997, we merged records from all VA inpatient and outpatient files. PRINCIPAL
      FINDINGS: Adding indicators for patients with mild/moderate SA disorders did not
      appreciably improve the R-squares for any of the outcome measures. When
      indicators were added for patients with severe SA who were in the most costly
      category, the explanatory ability of the models was modestly improved for all
      three outcomes. CONCLUSIONS: Modifying the DCG/HCC model with additional markers
      for SA modestly improved homogeneity and model prediction. Because considerable
      variation still remained after modeling, we conclude that health care systems
      should evaluate "off-the-shelf" risk adjustment systems before applying them to
      their own populations.

PMID- 12236386
TI  - Managed behavioral health care: an instrument to characterize critical elements
      of public sector programs.
AB  - OBJECTIVE: To develop an instrument to characterize public sector managed
      behavioral health care arrangements to capture key differences between managed
      and "unmanaged" care and among managed care arrangements. STUDY DESIGN: The
      instrument was developed by a multi-institutional group of collaborators with
      participation of an expert panel. Included are six domains predicted to have an
      impact on access, service utilization, costs, and quality. The domains are:
      characteristics of the managed care plan, enrolled population, benefit design,
      payment and risk arrangements, composition of provider networks, and
      accountability. Data are collected at three levels: managed care organization,
      subcontractor, and network of service providers. DATA COLLECTION METHODS: Data
      are collected through contract abstraction and key informant interviews. A
      multilevel coding scheme is used to organize the data into a matrix along key
      domains, which is then reviewed and verified by the key informants. PRINCIPAL
      FINDINGS: This instrument can usefully differentiate between and among Medicaid
      fee-for-service programs and Medicaid managed care plans along key domains of
      interest. Beyond documenting basic features of the plans and providing contextual
      information, these data will support the refinement and testing of hypotheses
      about the impact of public sector managed care on access, quality, costs, and
      outcomes of care. CONCLUSIONS: If managed behavioral health care research is to
      advance beyond simple case study comparisons, a well-conceptualized set of
      instruments is necessary.

PMID- 12236387
TI  - Medicaid enrollment among elderly medicare beneficiaries: individual
      determinants, effects of state policy, and impact on service use.
AB  - OBJECTIVE: To better understand factors associated with Medicaid enrollment among
      low-income, community-dwelling elderly persons and to examine the effect of
      Medicaid enrollment on the use of health care services by elderly persons, taking
      into account selection in program participation. DATA SOURCES: 1996 Medicare
      Current Beneficiary Survey (MCBS) Access to Care and Cost and Use files. METHODS:
      Individual-level predictions of the probability of dual enrollment are obtained
      from equations that estimate jointly the residential status of Medicare
      beneficiaries (community versus institution) and the probability of Medicaid
      enrollment among community-dwelling eligible beneficiaries. Predicted values are
      then substituted into the service use equations, which are estimated via two-part
      models. PRINCIPAL FINDINGS: Less than half of all community-dwelling elderly
      persons with incomes at or below 100 percent of the Federal Poverty Level (FPL)
      were enrolled in Medicaid in 1996. Once selective enrollment was accounted for,
      there was limited evidence of a dual enrollment effect on service use. Although
      there were no effects of state Medicaid policy variables on the probability that
      beneficiaries lived in the community (as opposed to nursing homes), the effects
      of state's Medicaid generosity in home and community-based services had a
      sizeable and statistically significant effect on influencing the likelihood that
      eligible elderly persons enrolled in Medicaid. CONCLUSIONS: Our results provide
      compelling evidence that Medicaid participation can be influenced by state
      policy. The observation that "policy matters" provides new insights into how
      existing programs might reach a larger proportion of potentially eligible
      beneficiaries.

PMID- 12236388
TI  - The 2030 problem: caring for aging baby boomers.
AB  - OBJECTIVE: To assess the coming challenges of caring for large numbers of frail
      elderly as the Baby Boom generation ages. STUDY SETTING: A review of economic and
      demographic data as well as simulations of projected socioeconomic and
      demographic patterns in the year 2030 form the basis of a review of the
      challenges related to caring for seniors that need to be faced by society. STUDY
      DESIGN: A series of analyses are used to consider the challenges related to
      caring for elders in the year 2030: (1) measures of macroeconomic burden are
      developed and analyzed, (2) the literatures on trends in disability, payment
      approaches for long-term care, healthy aging, and cultural views of aging are
      analyzed and synthesized, and (3) simulations of future income and assets
      patterns of the Baby Boom generation are developed. PRINCIPAL FINDINGS: The
      economic burden of aging in 2030 should be no greater than the economic burden
      associated with raising large numbers of baby boom children in the 1960s. The
      real challenges of caring for the elderly in 2030 will involve: (1) making sure
      society develops payment and insurance systems for long-term care that work
      better than existing ones, (2) taking advantage of advances in medicine and
      behavioral health to keep the elderly as healthy and active as possible, (3)
      changing the way society organizes community services so that care is more
      accessible, and (4) altering the cultural view of aging to make sure all ages are
      integrated into the fabric of community life. CONCLUSIONS: To meet the long-term
      care needs of Baby Boomers, social and public policy changes must begin soon.
      Meeting the financial and social service burdens of growing numbers of elders
      will not be a daunting task if necessary changes are made now rather than when
      Baby Boomers actually need long-term care.

PMID- 12236389
TI  - The impact of financial incentives on physician productivity in medical groups.
AB  - OBJECTIVE: To estimate the effect of financial incentives in medical groups--both
      at the level of individual physician and collectively--on individual physician
      productivity. DATA SOURCES/STUDY SETTING: Secondary data from 1997 on individual
      physician and group characteristics from two surveys: Medical Group Management
      Association (MGMA) Physician Compensation and Production Survey and the Cost
      Survey Area Resource File data on market characteristics, and various sources of
      state regulatory data. STUDY DESIGN: Cross-sectional estimation of individual
      physician production function models, using ordinary least squares and two-stage
      least squares regression. DATA COLLECTION: Data from respondents completing all
      items required for the two stages of production function estimation on both MGMA
      surveys (with RBRVS units as production measure: 102 groups, 2,237 physicians;
      and with charges as the production measure: 383 groups, 6,129 physicians). The
      102 groups with complete data represent 1.8 percent of the 5,725 MGMA member
      groups. PRINCIPAL FINDINGS: Individual production-based physician compensation
      leads to increased productivity, as expected (elasticity = .07, p < .05). The
      productivity effects of compensation methods based on equal shares of group net
      income and incentive bonuses are significantly positive (p < .05) and smaller in
      magnitude. The group-level financial incentive does not appear to be
      significantly related to physician productivity. CONCLUSIONS: Individual
      physician incentives based on own production do increase physician productivity.

PMID- 12236390
TI  - Initial practice locations of international medical graduates.
AB  - OBJECTIVE: To examine the influence of place of graduate medical education (GME),
      state licensure requirements, presence of established international medical
      graduates (IMGs), and ethnic communities on the initial practice location choices
      of new IMGs. DATA SOURCES: The annual Graduate Medical Education (GME) Survey of
      the American Medical Association (AMA) and the AMA Physician Masterfile. STUDY
      DESIGN: We identified 19,940 IMGs who completed GME in the United States between
      1989 and 1994 and who were in patient care practice 4.5 years later. We used
      conditional logit regression analysis to assess the effect of market area
      characteristics on the choice of practice location. The key explanatory variables
      in the regression models were whether the market area was in the state of GME,
      the years of GME required for state licensure, the proportion of IMGs among
      established physicians, and the ethnic composition of the market area. PRINCIPAL
      FINDINGS: The IMGs tended to locate in the same state as their GME training.
      Foreign-born IMGs were less likely to locate in markets with more stringent
      licensure requirements, and were more likely to locate in markets with higher
      proportions of established IMG physicians. The IMGs born in Hispanic or Asian
      countries were more likely to locate in markets with higher proportions of the
      corresponding ethnic group. CONCLUSIONS: Policymakers may influence the flow of
      new IMGs into states by changing the availability of GME positions. IMGs tend to
      favor the same markets over time, suggesting that networks among established IMGs
      play a role in attracting new IMGs. Further, IMGs choose their practice locations
      based on ethnic matching.

PMID- 12236391
TI  - Predicting patterns of mammography use: a geographic perspective on national
      needs for intervention research.
AB  - OBJECTIVE: To introduce a methodology for planning preventive health service
      research that takes into account geographic context. DATA SOURCES: National
      Health Interview Survey (NHIS) self-reports of mammography within the past two
      years, 1987, and 1993-94. Area Resource File (ARF), 1990. Database of mammography
      intervention research studies conducted from 1984 to 1994. DESIGN: Bayesian
      hierarchical modeling describes mammography as a function of county-level
      socioeconomic data and explicitly estimates the geographic variation unexplained
      by the county-level data. This model produces county use estimates (both NHIS
      sampled and unsampled), which are aggregated for entire states. The locations of
      intervention research studies are examined in light of the statewide mammography
      utilization estimates. DATA EXTRACTION: Individual level NHIS data were merged
      with county-level data from the ARF. PRINCIPAL FINDINGS: State maps reveal the
      estimated distribution of mammography utilization and intervention research.
      Eighteen states with low mammography use reported no intervention research
      activity. County-level occupation and education were important predictors for
      younger women in 1993-94. In 1987, they were not predictive for any demographic
      group. CONCLUSIONS: Opportunities exist to improve the planning of future
      intervention research by considering geographic context. Modeling results suggest
      that the choice of predictors be tailored to both the population and the time
      period under study when planning interventions.

PMID- 12236392
TI  - Physician referral patterns and race differences in receipt of coronary
      angiography.
AB  - OBJECTIVE: This study addresses the following research questions: (1) Is race a
      predictor of obtaining a referral for coronary angiography (CA) among patients
      who are appropriate candidates for the procedure? (2) Is there a race disparity
      in obtaining CA among patients who obtain a referral for the procedure? STUDY
      SETTING: Three community hospitals in Baltimore, Maryland. STUDY DESIGN: We
      abstracted hospital records of 7,927 patients from three hospitals to identify
      2,653 patients who were candidates for CA. Patients were contacted by telephone
      to determine if they received a referral for CA. Logistic regression was used to
      assess whether racial differences in obtaining a referral were affected by
      adjustment for several potential confounders. A second set of analyses examined
      race differences in use of the procedure among a subsample of patients that
      obtained a referral. PRINCIPAL FINDINGS: After controlling for having been
      hospitalized at a hospital with in-house catheterization facilities, ACC/AHA
      (American College of Cardiology/American Heart Association) classification, sex,
      age, and health insurance status, race remained a significant determinant of
      referral (OR = 3.0, p < .05). Additionally, we found no significant race
      differences in receipt of the procedure among patients who obtained a referral.
      CONCLUSIONS: Our results demonstrate that race differences in utilization of CA
      tend to occur during the process of determining the course of treatment. Once a
      referral is obtained, African American patients are not less likely than white
      patients to follow through with the procedure. Thus, future research should seek
      to better understand the process by which the decision is made to refer or not
      refer patients.

PMID- 12236393
TI  - The determinants of HMOs' contracting with hospitals for bypass surgery.
AB  - OBJECTIVE: Selective contracting with health care providers is one of the
      mechanisms HMOs (Health Maintenance Organizations) use to lower health care costs
      for their enrollees. However, are HMOs compromising quality to lower costs? To
      address this and other questions we identify factors that influence HMOs'
      selective contracting for coronary artery bypass surgery (CABG). STUDY DESIGN:
      Using a logistic regression analysis, we estimated the effects of hospitals'
      quality, costliness, and geographic convenience on HMOs' decision to contract
      with a hospital for CABG services. We also estimated the impact of HMO
      characteristics and market characteristics on HMOs' contracting decision. DATA
      SOURCES: A 1997 survey of a nationally representative sample of 50 HMOs that
      could have potentially contracted with 447 hospitals. PRINCIPAL FINDINGS: About
      44 percent of the HMO-hospital pairs had a contract. We found that the
      probability of an HMO contracting with a hospital increased as hospital quality
      increased and decreased as distance increased. Hospital costliness had a negative
      but borderline significant (0.10 < p < 0.05) effect on the probability of a
      contract across all types of HMOs. However, this effect was much larger for IPA
      (Independent Practice Association)-model HMOs than for either group/staff or
      network HMOs. An increase in HMO competition increased the probability of a
      contract while an increase in hospital competition decreased the probability of a
      contract. HMO penetration did not affect the probability of contracting. HMO
      characteristics also had significant effects on contracting decisions.
      CONCLUSIONS: The results suggest that HMOs value quality, geographic convenience,
      and costliness, and that the importance of quality and costliness vary with HMO.
      Greater HMO competition encourages broader hospital networks whereas greater
      hospital competition leads to more restrictive networks.

PMID- 12236395
TI  - Looking forward to impact: moving beyond serendipity.

PMID- 12236394
TI  - Effects of CAHPS health plan performance information on plan choices by New
      Jersey Medicaid beneficiaries.
AB  - OBJECTIVE: To assess the effects of CAHPS health plan performance information on
      plan choices and decision processes by New Jersey Medicaid beneficiaries. DATA
      SOURCES/STUDY SETTING: The study sample was a statewide sample of all new
      Medicaid cases that chose Medicaid health plans during April 1998. The study used
      state data on health maintenance organization (HMO) enrollments and survey data
      for a subset of these cases. STUDY DESIGN: An experimental design was used, with
      new Medicaid cases randomly assigned to experimental or control groups. The
      experimental group received a CAHPS report along with the standard enrollment
      materials, and the control group did not. DATA COLLECTION: The HMO enrollment
      data were obtained from the state in June 1998, and evaluation survey data were
      collected from July to October 1998. PRINCIPAL FINDINGS: No effects of CAHPS
      information on HMO choices were found for the total sample. Further examination
      revealed that only about half the Medicaid cases said they received and read the
      plan report and there was an HMO with dominant Medicaid market share but low
      CAHPS performance scores. The subset of cases who read the report and did not
      choose this dominant HMO chose HMOs with higher CAHPS scores, on average, than
      did those in an equivalent control group. CONCLUSIONS: Health plan performance
      information can influence plan choices by Medicaid beneficiaries, but will do so
      only if they actually read it. These findings suggest a need for enhancing
      dissemination of the information as well as further education to encourage
      informed choices.

PMID- 12236396
TI  - Release of medical records: current status of Louisiana law.

PMID- 12236397
TI  - ECG of the month. Pairs. Ventricular bigeminal rhythm.

PMID- 12236398
TI  - Radiology case of the month. Knee pain in a 40-year-old woman. Langerhans cell
      histiocytosis (LCH) vs. Brodie's Abscess.

PMID- 12236399
TI  - Pathology case of the month. Elderly woman with fatigue. The 5q- Syndrome.

PMID- 12236401
TI  - Management of acute ST-segment elevation myocardial infarction. I. Reperfusion
      therapy.

PMID- 12236400
TI  - Lymphoma or pseudolymphoma?
AB  - Anticonvulsant hypersensitivity syndrome is a systemic illness that presents most
      commonly as a triad of fever, rash, and lymphadenopathy in a patient exposed to
      one or more of the aromatic antiepileptic drugs (phenytoin, phenobarbital, and
      carbamazepine). Although generally self-limited, the syndrome may be life
      threatening, particularly among patients who develop severe cutaneous eruptions
      or hepatitis. Early recognition of the syndrome is essential, as immediate
      discontinuation of the offending antiepileptic agent is the most important step
      in improving outcome. We present a case of anticonvulsant hypersensitivity
      syndrome in a patient with a previous history of Hodgkin's lymphoma.

PMID- 12236402
TI  - Geriatric medical education in Louisiana: current status and future needs.
AB  - Despite the impending explosion in the size of American's elderly population,
      physicians remain undertrained in geriatric medicine. In Louisiana, this training
      is especially important for the family physician and internist, many of whom
      practice primarily in rural areas and carry the bulk of nursing home patient care
      on their shoulders. Louisiana's medical schools offer little in the way of
      training in geriatric medicine, despite the author's finding that there is a
      strong interest for such training among practitioners and residents. Meanwhile,
      at the national level, leaders in geriatric medicine are working to develop new
      ways to encourage participation in geriatric educational opportunities.

PMID- 12236403
TI  - Sharper focus on sickle cell anemia.

PMID- 12236404
TI  - Primary carcinoma of the gall bladder: a review of our experience.
AB  - Carcinoma of the gallbladder is a rare, but deadly, cancer of the
      gastrointestinal tract. A retrospective review of 29 medical records of patients
      with primary carcinoma of the gallbladder was performed. Twenty-eight patients
      (96%) were age 50 or greater at diagnosis. The most common presenting symptom was
      abdominal pain (82.7%), followed by nausea and vomiting (44.8%). An ultrasound of
      the gallbladder was the most common pre-operative study (72.4%). Seventy-one
      percent of ultrasounds revealed only cholelithiasis. Symptomatic cholelithiasis
      was the most common pre-operative diagnosis (48.2%). Laparoscopic cholecystectomy
      was performed in 9 (31%) patients. All patients with carcinoma in situ, stage I,
      and stage II disease were living at last follow up. Average survival after
      diagnosis for stage III disease was 5.7 months, and for stage IV disease was 3.1
      months. Our results and that of others lead us to believe that in any patient
      with a pre-operative or intra-operative suspicion of gallbladder cancer an open
      procedure is indicated. Furthermore, we believe that laparoscopic cholecystectomy
      may be inadequate and contraindicated in all but carcinoma in situ and stage I
      disease.

PMID- 12236405
TI  - Dieulafoy's ulcer: proximal extra-gastric arterial ligation--a case report and
      review of the literature.

PMID- 12236406
TI  - Now and in retrospect: Louisiana lues.
AB  - This article gives a brief descriptive synopsis of the disease syphilis and
      presents in narrative and graphic form current statistics and those of the recent
      past of the incidence of syphilis cases in Louisiana. The latest recommendations
      for treatment of all stages of syphilis from the U.S. Public Health Service
      Centers for Disease Control and Prevention are included.

PMID- 12236407
TI  - Depressive disorders and alcohol dependence in a community population.
AB  - This cross-sectional study examines sociodemographic, clinical and func tional
      correlates of comorbid depression in a community sample of 268 individuals with
      alcohol dependence. Results of analyses comparing drinkers with either current or
      past depression to never-depressed drinkers showed that respondents in the former
      two groups were more likely to be female and report more comorbid drug use
      disorders. In addition to marked functional impairment for currently depressed
      drinkers, we also found that respondents with past depression were significantly
      less likely to have health insurance coverage. This lack of insurance for
      previously depressed persons calls for future work examining the potential
      influence of this barrier to access care on both clinical and functional
      outcomes.

PMID- 12236408
TI  - A strength-based and early relationship approach to infant mental health
      assessment.
AB  - This paper presents a strength-based assessment process that focuses on infant
      emotional development within the family context. The assessment model, developed
      over the past five years within a preventive mental health program, represents a
      shift from deficit to strength-based principles that are consistent with
      appropriate developmental practice. The strength-based assessment process
      presented achieves an understanding of the infant's competencies and areas of
      need, and considers the negative impact that maternal mental illness has on the
      infant's emotional development.

PMID- 12236409
TI  - Perceptions of problems and needs for service among middle-aged and elderly
      outpatients with schizophrenia and related psychotic disorders.
AB  - We examined the perceived problems and needs for services among 72 middle-aged
      and elderly outpatients with schizophrenia and related psychotic disorders. The
      survey questionnaire included 50 Likert scaled items involving everyday
      functioning skills, health, clinical symptoms, and social skills. Subjects
      assigned the highest priority to physical health and memory. Other areas of high
      priority were: social functioning, education about their own mental illness, and
      improvements in sleep and mood. Reducing frequency of psychiatric
      hospitalization, and drug or alcohol rehabilitation received low priority.
      Focused interventions targeting health-related and social issues are needed in
      older patients with schizophrenia.

PMID- 12236410
TI  - Enhancement of executive functioning skills: an additional tier in the treatment
      of schizophrenia.
AB  - Schizophrenia is viewed by most as having a neuropsychological component, with
      deficits primarily occurring in the areas of attention/concentration, memory, and
      executive functioning. These deficits often contribute to difficulties in
      everyday living and social functioning. The purpose of this study is to examine
      the efficacy of cognitive rehabilitation methods, typically utilized by brain
      injured patients, to improve the executive functioning skills of patients with
      schizophrenia spectrum disorders. While this pilot study is limited in terms of
      sample size, results suggest that the addition of cognitive rehabilitation to the
      comprehensive treatment of schizophrenia could be beneficial in enhancing daily
      living skills.

PMID- 12236411
TI  - Family-responsive psychoeducation groups for families with an adult member with
      mental illness: pilot results.
AB  - This paper documents recent pilot efforts of the Psychoeducation Responsive to
      Family (PERF) model, a yearlong group for families with an adult member coping
      with mental illness. PERF advances state-of-the-art in its: (a) application in
      community settings; (b) utility for families coping with all types of mental
      illness; (c) use of a standardized model, yet retaining a flexible curriculum
      responsive to family group membership concerns; and (d) recruitment from one-day
      family workshops of participants eager to further explore their issues. This
      report examines changes in these families' knowledge and mastery in a small
      random assignment study comparing the PERF model (n = 9) with a "usual services"
      (n = 10) condition. Study participants completed surveys measuring perceived
      mastery and knowledge at baseline and at 3, 6, and 12 months for both conditions.
      Families in the active PERF intervention demonstrated significant post
      intervention improvements in four of five variables analyzed. For one of these
      items, PERF demonstrated significantly greater improvement than the usual care
      condition. Achievement of significant changes in these measures was examined in
      relation to timing of presentation of curriculum topics in the groups. Gains in
      perceived crisis effectiveness temporally correlated with coverage of that topic
      in the PERF groups, while gains in other items were instead steadily cumulative
      across the entire year. The encouraging results of this second pilot effort serve
      to substantiate the initial efforts in developing the PERF group model.

PMID- 12236412
TI  - Assertive community treatment in Amsterdam.
AB  - In Amsterdam in the Netherlands, in 1993, an intensive case management project
      was initiated. This article describes this well-known Dutch project as it was
      tested in a randomised clinical trial using regular outpatient and inpatient care
      as the control conditions. All the patients in this project are very ill and most
      of them suffer from schizophrenia. The new form of care has the same effect on
      everyday problems as regular care. The basis of this data is too narrow for the
      drawing of conclusions about the risk of suicide. Longer follow-up would be
      advisable in order to improve our understanding of this problem. There has been
      no drop in compulsory admissions. On the other hand, there has been a spectacular
      decrease in the number of bed days (a reduction of 66% in the second year of the
      ACT programme).

PMID- 12236413
TI  - The protective immunity produced in infected C57BL/6 mice of a DNA vaccine
      encoding Schistosoma japonicum Chinese strain triose-phosphate isomerase.
AB  - The development of a SjCTPI DNA vaccine for Schistosoma japonicum and the
      detection of the immune responses to and the protective efficacy of immunization
      were performed and challenged in C57BL/6 mice. According to the gene sequence of
      SjCTPI and murine IL-12, three pairs of primers were designed. The full length
      cDNA encoding SjCTPI and P35, P40 amplified from pUC19-SjCTPI and murine IL-12 by
      PCR were subcloned into an eukaryotic expression vector (pcDNA3.1). Forty-five
      female C57BL/6 mice were divided into three groups; each mouse of the control
      group was injected with 100 pg of pcDNA3.1 by i.m. route; the TPI group was
      injected with 100 microg of pcDNA3. 1-SjCTPI; the TPI+IL- 12 group was injected
      with 100 microg of pcDNA3.1-SjCTPI and 100 pg of mixture of pcDNA3.1-P35 and
      pcDNA3.1-P40. Each mouse was immunized at weeks 1 and 5 and challenged with 45
      cercariae of Schistosoma japonicum Chinese strain at week 9. The mice were killed
      and perfused 45 days after challenge; the numbers of recovered worms and hepatic
      eggs were counted. The expression of SjCTPI in muscle tissue was determined by an
      immunohistochemical method. Culture of spleen cells showed the production of IL
      2, IL-4, IL-10 and IFN-gamma with the stimulation of specific antigen before and
      after challenge. Sera were collected from each group before immunization, before
      challenge and two weeks post challenge; ELISA and Western-blot tests were
      performed for detection of anti-rTPI antibodies. The antigen of SjCTPI was
      expressed in the membrane and plasma of the muscle cells of C57BL/6 mice. The
      obvious rising of IL-2 in TPI group and TPI+IL-12 group before and after
      challenge was seen. The anti-rTPI antibody detection with Western-blot showed
      that ten serum samples from the control group were negative; nine of ten serum
      samples from the TPI group were weakly positive, eight of ten from the TPI+IL-12
      group were weakly positive. The worm and egg reduction rates of TPI group and
      TPI+IL- 12 group were 27.9% and 13.7%, 31.9% and 18.6% respectively in comparison
      with the pcDNA group. pcDNA3.1-TPI DNA vaccine could confer partial protection
      against a subsequent challenge of Schistosoma japonicum in C57BL/6 mice and might
      therefore be a potential DNA vaccine.

PMID- 12236414
TI  - Intestinal helminthiases and their control with albendazole among primary
      schoolchildren in riverine communities of Ondo State, Nigeria.
AB  - A study to establish the prevalence of intestinal helminthiases among
      schoolchildren of riverine communities in the Ilaje-Ese Odo Local Government Area
      of Ondo State, Nigeria was conducted. Ninety-four percent of the children studied
      were infected with intestinal helminths. Trichuris trichiura infection was the
      commonest (84%), followed by Ascaris lumbricoides (75.3 %) and hookworm (7.6 %).
      Dual helminthic infections were recorded, with Ascaris-Trichuris having the
      highest prevalence among the children. Poor environmental sanitation and personal
      hygiene combined with the absence of potable water and a lack of awareness of the
      effects of nematode infection were identified as the possible reasons for the
      high rate of infection. Treatment with albendazole (200 mg) brought about
      reductions in the level of Trichuris trichiura (to 41.7%), Ascaris lumbricoides
      (to 4.2%) and Hookworm (to 0.7%). The estimated rates of reduction were 94.4%,
      49.7%, and 90.2% for Ascaris lumbricoides, Trichuris trichiura and hookworm
      respectively. Post-treatment helminthic reduction, as found in this study, is
      expected to enhance the mental and physical development of the children.
      Community mobilization with health education messages aimed at improving personal
      and community hygiene was initiated with an emphasis on creating a sustained
      reduction in the burden of helminthic infection.

PMID- 12236415
TI  - A cross-sectional study of intestinal parasitic infections among schoolchildren
      in Nan Province, Northern Thailand.
AB  - A cross-sectional study of the prevalence of intestinal parasitic infections at
      eight schools in Bo Klau district and four schools in Chalerm Prakiet district,
      Nan Province, in January and February, 2001. A total of 1,010 fecal samples were
      examined using the formalin-ether sedimentation technique. Results revealed that
      the rate of helminthic infection was 60.0%, while protozoa accounted for 36.2% of
      infections; mixed infections were common, resulting in a total prevalence of both
      parasites of 68.1%. Helminthic parasites, listed by frequency of infections, were
      Ascaris lumbricoides (21.7%), hookworm (18.5%), Trichuris trichiura (16.3%),
      Opisthorchis viverrini (1.7%), Strongyloides stercoralis (0.9%) and Enterobius
      vermicularis (0.9%). The protozoal infections were Entamoeba coli (25.8%),
      Giardia lamblia (5.3%), Endolimax nana (2.5%), Entamoeba histolytica (1.4%),
      Blastocystis hominis (0.8%), Chilomastix mesnili (0.3%) and Iodamoeba butschlii
      (0.1%). This study emphasizes the need for improved environmental hygiene ie
      clean water supplies and enhanced sanitation, in affected communities. Health
      promotion, by means of a school-based educational approach is recommended;
      regular check-ups should be implemented, and a continuos program of treatment
      should be considered.

PMID- 12236416
TI  - Trichuriasis: localized inflammatory responses in the colon.
AB  - Most patients with trichuriasis have light worm burdens. Data regarding the
      inflammatory response to Trichuris worms in the colon of lightly infected persons
      are scant. Nine patients whose Trichuris infection was found by colonoscopy had
      biopsies taken from a site adjacent to visible worms and from a second site some
      20 cm distally. The biopsies were studied by routine and immunohistochemical
      methods. None of the biopsies showed mucosal ulceration, significant congestion,
      fibrosis, gland distortion or goblet cell mucin depletion. There was no
      difference between worm and worm-free sites in terms of edema, lymphoid follicles
      or epithelial slough. Worm sites had higher numbers of eosinophils, neutrophils
      and total inflammatory cells and lower numbers of plasma cells. However there was
      no difference in lymphocyte, mast cell, and B- and T-cell counts between the two
      sites. This suggests that the T. trichiura worm incites a local inflammatory
      response involving eosinophils and neutrophils, even when the colon has only a
      light burden of worms.

PMID- 12236417
TI  - Diphyllobothriasis: the first case report from Malaysia.
AB  - Diphyllobothriasis is a disease caused by infection with adult tapeworms of the
      genus Diphyllobothrium. Humans acquire the infection by consuming the raw or
      inadequately cooked flesh, roe, liver, or other organs of infected fish.
      Diphyllobothrium latum infection has not been reported in Malaysia; we are
      reporting the first case. The patient was a 62 year old Chinese male seen at the
      outpatient clinic with complaints of watery stools and slight abdominal
      discomfort for four days. Physical examination was normal. He was treated for
      diarrhea. Two days after treatment, he passed out intact off-white proglottids in
      his stool. Diphyllobothriasis was confirmed by examination of these gravid
      proglottids; typical operculated eggs were seen after rupturing the gravid
      proglottids. The patient had a history of eating sashimi (Japanese raw fish). He
      was treated with a single dose of praziquantel and had been well since.

PMID- 12236418
TI  - Clinical manifestations and outcome of patients with severe eosinophilic
      meningoencephalitis presumably caused by Angiostrongylus cantonensis.
AB  - The clinical manifestations and outcome of patients with severe eosinophilic
      meningoencephalitis has never been reported. We reported 11 comatose patients
      with eosinophilic meningoencephalitis. Most of them presented with subacute to
      chronic headache and fever, followed by acute coma. Cerebrospinal fluid
      abnormalities were similar to alert patients with eosinophilic meningitis. None
      of them had received antihelmintic drug and seven patients were treated with
      corticosteroids. Ten patients died and one patient is still in a coma.
      Corticosteroids seem to be ineffective in severe eosinophilic meningitis.

PMID- 12236419
TI  - Clone of the gene of the dense granule antigen (GRA6) of the Toxoplasma gondii
      pig strain.
AB  - The gene of GRA6 of Toxoplasma gondii pig strain was cloned; and the value of
      recombinant GRA6 as a diagnostic antigen of toxoplasmosis in China was
      investigated. A pair of primers was synthesized according to the DNA sequence of
      GRA6 of T. gondii RH strain, and the DNA of pig strain tachyzoites was prepared.
      A single, specific DNA fragment was successfully amplified from the genomic DNA
      of tachyzoites of T. gondii. This gene fragment was cloned into the plasmid pUC19
      to form the recombinant. The recombinant plasmid was purified and the foreign DNA
      fragment was sequenced. The result of DNA sequencing showed that the open reading
      frame of GRA6 is composed of 693 base pairs and encodes 230 amino acids and is
      100% homologous with the sequence of GRA6 of T. gondii RH strain.

PMID- 12236420
TI  - Intestinal microsporidiosis in HIV-infected children with diarrhea.
AB  - Intestinal microsporidiosis is a common opportunistic disease associated with
      diarrhea in adult AIDS patients in Thailand; the data regarding this infection in
      children are scarce. The present study was designed to investigate the prevalence
      and clinical features of intestinal microsporidiosis in hospitalized HIV-infected
      and uninfected (free of HIV) children with diarrhea. Of the 95 HIV-infected
      children and 87 uninfected children, 24 (25.3%) and 13 (14.9%) respectively were
      diagnosed with intestinal microsporidiosis. Species identification of
      microsporidia spores, by transmission electron microscopy, demonstrated
      Enterocytozoon bieneusi in 5 cases. Cryptosporidium parvum was a common
      coinfective parasite; pneumonia was the most frequent concurrent disease found in
      children with intestinal microsporidiosis. Malnutrition was commoner in the HIV
      infected group (79.2% vs 23.1%; p = 0.003). This study indicates that intestinal
      microsporidiosis is an important disease in both HIV-infected and uninfected Thai
      children with diarrhea.

PMID- 12236421
TI  - Knowledge and behavior relating to malaria in malaria endemic villages of
      Khammouane Province, Lao PDR.
AB  - In order to provide basic data for evaluation of malaria control measures, a
      study on the knowledge and behavior of people regarding prevention of malaria was
      carried out in 8 malaria endemic villages in Khammouane Province of Lao PDR from
      1999 to 2000. The total valid questionnaire respondents were 932, with a mean age
      of 32.3 +/- 14.9. 43.7% of the respondents were illiterate. About 44% of the
      respondents suffered from malaria in the past. About 55% of the illiterate group
      slept in mosquito nets, compared to 75.4% for the educated group. About 29% of
      the illiterate respondents had knowledge of malaria transmission by mosquito
      bites, compared to 48.8% for the educated groups. Out of 167 non-impregnated
      mosquito nets examined in two villages, 13 were in bad condition having holes or
      leaks and 39 female mosquitos including Anopheles spp were collected in these
      nets by early morning catches. Knowledge of malaria and behavior in relation to
      the prevention of malaria were significantly related to educational level. Health
      education as well as general education must be taken into account for communities
      in malaria endemic areas to become more involved in malaria control strategies.

PMID- 12236422
TI  - A comparison of the age distributions in the dengue hemorrhagic fever epidemics
      in Santiago de Cuba (1997) and Thailand (1998).
AB  - The age profiles of the infected populations of two dengue hemorrhagic fever
      (DHF) epidemics, the 1997 epidemic, in Santiago de Cuba and the 1998 epidemic in
      Thailand, are compared. Using an age-structured model of disease transmission,
      the dependence of the forces of infection on age was determined for each
      epidemic. The difference in the behavior of the two epidemics and the role of
      primary and secondary infection in the development of DHF are discussed.

PMID- 12236423
TI  - Reactogenicity and immunogenicity of a varicella vaccine in healthy seronegative
      and seropositive subjects.
AB  - The epidemiology of varicella appears to be changing: an unexplained upward age
      shift in varicella prevalence and a subsequent dramatic rise in morbidity and
      mortality among adolescents and adults have highlighted the importance of
      effective varicella mass vaccination programs. This age shift is being seen in
      temperate regions but is particularly marked in tropical and sub-tropical
      regions. To assess the need for serological pre-screening in mass vaccination
      programs, we performed an open study to compare the reactogenicity and
      immunogenicity of a varicella vaccine in initially seronegative and seropositive
      subjects to see whether there was an increase in reactogenicity among initially
      seropositive subjects. Two hundred and forty-six seronegative and seropositive
      male and female subjects, aged 9 months to 60 years, received a single dose of a
      live attenuated varicella virus (Oka-strain) vaccine, Varilrix (GlaxoSmithKline
      Biologicals, Rixensart, Belgium). Subjects were categorized according to antibody
      status and age group; serum antibodies were measured before and after vaccination
      (day 42). The study showed that there was no difference in reactogenicity in
      initially seropositive vaccinees compared with initially seronegative subjects.
      The varicella vaccine was found to be safe and well tolerated in all age groups.
      Ninety-eight percent of initially seropositive and 94.8% of initially
      seronegative subjects reported no clinical signs or symptoms during the 42-day
      follow-up period. The vaccine was immunogenic in both groups. The seroconversion
      rate after 6 weeks in initially seronegative subjects was 94.3%. In 53.0% of
      initially seropositive subjects of all age classes, a 4-fold rise in antibody
      titer was observed.

PMID- 12236424
TI  - Present epidemiological pattern of antibody to hepatitis a virus among Chiang Mai
      children, Northern Thailand.
AB  - Hepatitis A virus (HAV) infection is common in Southeast Asia, and most of the
      inhabitants acquire a lifelong immunity as a result of natural infection during
      childhood. However, the age-specific seroprevalence is changing with development
      of socioeconomic and hygiene status in this area and the infection is predicted
      to shift to adulthood with more severe clinical manifestations in the future. In
      this study, we report the present epidemiological pattern of antibody to HAV
      (anti-HAV) among schoolchildren in Chiang Mai, Northern Thailand. The overall
      prevalence rate of anti-HAV was 9.6% (11.4% in female and 7.5% in male children,
      and 10.8% in urban and 8.9% in rural schoolchildren, respectively). Our study,
      comparing with previous reports from other parts in Thailand, indicates a steady
      decline of anti-HAV prevalence among schoolchildren in Chiang Mai area, and
      discussed a possibility of an outbreak of HAV infection among urban
      schoolchildren.

PMID- 12236425
TI  - Seroprevalence of hepatitis B, hepatitis C and human immunodeficiency virus among
      blood donors, Phitsanulok Regional Blood Center, Thailand.
AB  - Human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus
      (HBV) infections are important blood-borne infections in many countries including
      Thailand. For epidemiological surveillance and controlling these infections, a
      cross-sectional group of 2,167 blood donors were screened for HBsAg, antibodies
      to HCV and HIV by enzyme immunoassay methods. The results revealed that the
      prevalence of HBsAg positive among studied blood donors was 4.61%, anti-HCV was
      2.90% and anti-HIV was 0.69%. When the prevalence was classified by selected
      socio-demographic variables, it was found that variables including age, gender,
      marital status and occupation were significant for HBsAg positive rate (p=0.0068,
      p=0.0019, p=0.0048 and p=0.0017, respectively). For anti-HCV prevalence, studied
      variables including educational level, occupation and domicile were significant
      (p<0.0001, p=0.0027, and p<0.0001, respectively), while only educational level
      was a significant variable for anti-HIV prevalence (p=0.0021). These findings
      suggest that we should present integrated information and educational programs
      for preventing and controlling HBV, HCV and HIV transmission among this target
      group.

PMID- 12236426
TI  - The efficacy of combined zidovudine and lamivudine compared with that of combined
      zidovudine, lamivudine and nelfinavir in asymptomatic and early symptomatic HIV
      infected children.
AB  - In this 6-month prospective study, we compared the efficacy of two treatment
      regimens: double-drug therapy with zidovudine (ZDV) and lamivudine (3TC) and
      triple-drug therapy with ZDV plus 3TC plus nelfinavir (NFV), in the treatment of
      asymptomatic and early symptomatic HIV-infected children. Twenty-five children
      were enrolled in this study and were divided into 2 groups: group A, consisting
      of 13 children who were given ZDV+3TC; group B, consisting of 12 children who
      were given ZDV+3TC+NFV. Serial determinations of weight, CD4-cell count, HIV RNA
      or plasma viral load (VL) and complete blood counts (CBC), liver function tests
      (LFT), blood urea nitrogen (BUN) tests, creatinine and serum amylase tests were
      performed at study entry and at 1, 3 and 6 months. The side-effects of drugs were
      recorded. Over the 6-month period, the median weight increase in group B (24%)
      was higher than in group A (2%). The median CD4-cell count increase from baseline
      in group B (94.5%) was better than in group A (9.4%). The reduction of VL below
      baseline in group B (1.2 log10; 20.8%) was also better than in group A (0.72
      log10; 13.8%). However, these differences were not statistically significant
      (p>0.05). Both combination regimens could not completely suppress HIV RNA below
      detectable limits (<400 copies/ml). Both groups tolerated the regimens well; no
      side-effects or toxicities occurred. The efficacy levels of triple-drug therapy
      (ZDV+3TC+NFV) and double-drug therapy (ZDV+3TC) were not different. There were no
      side-effects and no deaths during the 6-month study period.

PMID- 12236427
TI  - Recombinant envelope protein of HIV-1 subtype E as antigen in HIV-1 antibody
      detection enzyme immunoassay.
AB  - In order to develop a reliable and inexpensive serodiagnostic method to be used
      for anti-HIV antibody detection in Thailand, recombinant envelope (TM or gp41
      subunit) protein of HIV-1 subtype E was produced from prokaryotic cell
      (Escherichia coli) as the source of antigen in enzyme immunoassay (TE diagnostic
      EIA kit). HIV-1 gp41 subunit of subtype E was successfully expressed in E. coli
      in the form of polyhistidine-tagged proteins, comprising of rgp41A (601 bases N
      terminal half of TM or 25kDa) and rgp41B (560 bases C-terminal half of TM or 24
      kDa) by using an expression vector, pBAD/His C. The amount of protein, dilution
      of sera, and anti-human IgG labeled HRP used in the EIA test optimized by a
      checker board titration of the protein and seropositive or seronegative sera,
      were 5.0 microg/ml, 1:300, and 1:4,000, respectively. The blinded test evaluation
      of TE-diagnostic EIA in 500 seropositive and 500 seronegative sera which have
      been simultaneously tested by two available commercial kits and compared with our
      TE diagnostic EIA, gave 99.6% sensitivity and specificity. The other known
      genetic subtypes sera such as subtype A (n=5), B (n=9), C (n=4) and D (n=5) were
      also positive with this EIA. The estimated manufacturer cost per test of rgp41
      based anti-HIV antibody detection EIA or TE-diagnostic EIA was about 15 baht.
      This recombinant envelope (gp41 or TM) protein from HIV-1, which can be produced
      in large quantities without any hazards from growing the virus and has lower cost
      to produce anti-HIV antibody serological diagnostic kit, should be considered as
      an HIV screening test in Thailand.

PMID- 12236428
TI  - The seroprevalence of human herpesvirus 8 infection in the Thai population.
AB  - The seroprevalence of human herpesvirus 8 (HHV-8) infection in the Thai
      population was investigated. Sera from 1,018 human immunodeficiency virus 1 (HIV
      1)-negative and 436 HIV-1-positive individuals were tested for antibodies to
      latent and lytic HHV-8 antigens by indirect immunofluorescence assay (IFA) and an
      enzyme-linked immunosorbent assay (ELISA) using mixed recombinant orf HHV-8
      proteins. The positive sera were further tested with recombinant HHV-8 protein
      expressed 293T cells by IFA. The seroprevalence of HHV-8 infection was determined
      by the concordant reactivity of sera among antibody testing assays. The results
      showed a low rate of HHV-8 seropositivity in both HIV-1-negative healthy
      individuals (0.6%) and HIV-1-infected patients (0.7%). These results are
      consistent with the fact that a small number of patients with AIDS-associated KS
      have been reported in Thailand and that HHV-8 is an uncommon pathogen in this
      country. Interestingly, we found that sera from the general population living in
      the north, but not other regions of Thailand, had antibodies to HHV-8.

PMID- 12236429
TI  - Rapid diagnosis of cytomegalovirus in Thai pediatric AIDS patients.
AB  - Blood samples were collected from 100 pediatric AIDS patients for the detection
      of CMV in pp65-bearing leukocytes (PBLs) by immunoperoxidase staining (IP) and
      PCR. IgM antibody assay was performed to determine the correlation of antigen and
      antibody. IP and PCR can be used as methods for the early detection of CMV (prior
      to the presence of IgM antibody). The sensitivity and specificity of IP were 73%
      and 97% respectively. IP is superior to PCR in several ways: it is very easy to
      perform, less time consuming, less expensive, and does not require expensive
      instruments.

PMID- 12236430
TI  - Acute scrub typhus in Northern Thailand: EKG changes.
AB  - The electrocardiographic (EKG) manifestations of scrub typhus were prospectively
      evaluated in 29 adult patients who acquired Orientia tsutsugamushi infection in
      Chiang Rai, Northern Thailand. EKGs were normal in 22 of the 29 patients (76%);
      minor non-specific changes were found in the other 7 patients; ie ST segment/T
      wave changes (10%), U waves (7%), and premature ventricular contractions (4%).
      These results suggest that EKG changes in scrub typhus acquired in areas of
      diminished antibiotic susceptibility are similar to those observed in O.
      tsutsugamushi infection acquired elsewhere.

PMID- 12236431
TI  - The use of the indirect immunoperoxidase test for the serodiagnosis of
      rickettsial diseases in Malaysia.
AB  - The indirect immunoperoxidase (HP) test has been used extensively in most
      government hospitals in Malaysia for the serodiagnosis of scrub typhus, murine
      typhus and tick typhus during the 1990s. The test was used to determine the IgG
      and IgM antibody titers in patients' sera for three rickettsial species, ie
      Orientia tsutsugamushi OT; the causative agent of scrub typhus), Rickettsia typhi
      (RT; the causative agent of murine typhus), and TT118 spotted fever group
      rickettsiae (TT; the causative agent of tick typhus). The serological findings
      obtained from Malaysian hospitals using the IIP test (1994-1999) were analyzed.
      During the six-year period, a total of 61,501 patients' sera were tested, of
      which 9.6%, 10.5%, and 12.9% had antibody (IgG and/or IgM of > or = 1:50) for OT,
      RT and TT respectively. A total of 8.6%, 9.8%, and 9.7% of sera had IgG antibody
      of > or = 1:50 for OT, RT, and TT respectively, indicating past infection. A
      total of 3.4%, 3.8%, and 6.4 % of sera had IgM antibody of > or = 1:50 for OT,
      RT, and TT respectively, indicating recent infection. A total of 2,986 (4.9%),
      1,882 (3.1%), and 1,574 (2.6%) of sera had IgG and/or IgM antibody titers of > or
      = 1:400 for OT, RT, and TT respectively, suggesting active rickettsial infection.
      The seropositivity rates of OT, RT and TT varied according to geographical
      locations. While the seropositivity of OT remained constant during the six-year
      period, a reduction in the seropositivity of both RT and TT was noted during
      recent years. The serological findings reflect the endemicity of rickettsial
      diseases, including tick typhus, and endemic typhus in various parts of Malaysia.
      Awareness of these diseases by health and medical staff and by the general public
      is important if the mortality and morbidity associated with scrub typhus, tick
      typhus, and murine typhus in Malaysia, are to be reduced.

PMID- 12236432
TI  - Cost analysis of different types of tuberculosis patient at tuberculosis centers
      in Thailand.
AB  - Tuberculosis (TB) has recently re-emerged as a major public health problem in
      Thailand. As a consequence of the HIV epidemic in the country, the TB burden has
      been rising in terms of both morbidity, and mortality which have tremendous
      socioeconomic impact. However, a study of the cost of various anti-TB drugs in
      Thailand has never been conducted. A specific aim of this study was to compare
      the total provider costs of delivering services to different types of TB patient
      in four zonal TB centers located in the east, northeast, north, and south of
      Thailand. This aim was accomplished by calculating the unit costs of TB treatment
      services at these TB centers during the year 1996-1997. All units of the zonal TB
      centers were classified into 5 cost-center categories: treatment units,
      laboratory units, radiology units, pharmaceutical units, and
      administrative/supportive units. The results showed that the average total
      provider cost of multidrug resistant TB (MDR TB) patients was 89,735.49 baht
      which was the highest of any type of patient and was 17 times higher than the
      cost of smear-negative TB cases; this finding was attributed to the high cost of
      anti-TB drugs for MDR TB cases (65,870 baht), some 95 times higher than the cost
      for smear-negative cases. Total provider costs were highest in the northeastern
      region TB centers and lowest in the southern centers for every type of TB
      patient: smear-negative TB cases (7.727 baht vs 3.916 baht). newly smear positive
      TB cases (12,539 baht vs 7.020 baht), TB with AIDS cases (15,108 baht vs 8,369
      baht). re-treatment TB cases (16,679 baht vs 9,696 baht), and MDR TB cases
      (102.330 baht vs 82,933 baht). The information from this study may be useful when
      reviewing the role, function, and cost structure of each TB center in Thailand in
      order to establish a strategic plan for effective TB control.

PMID- 12236433
TI  - The spectrum of tuberculosis among patients of the King Abdul Aziz Unveristy
      Hospital, Jeddah, Saudi Arabia.
AB  - A retrospective study, reviewing the medical records of 157 patients with a final
      diagnosis of tuberculosis on discharge, was conducted at King Abdul Aziz
      University Hospital during the period July 1999 to July 2001. The data included
      demographic characteristics, the spectrum of clinical presentations, diagnostic
      methods, and the outcome of treatment. A total of 157 patients were admitted with
      tuberculosis; their median age was 33(+/- 15.33) years. Fifty-seven (36%) were
      Saudis and 100 (64%) were non-Saudis. Pulmonary tuberculosis and pleural effusion
      were the commonest presentations (37.6%). Diagnosis was confirmed in most cases
      by either a positive sputum smear for AFB or by pleural biopsy; in five patients
      the diagnosis was made on clinical grounds and pleural fluid analysis. There was
      a wide spectrum of extra-pulmonary tuberculosis, diagnosed histologically except
      in five cases, in which treatment was started empirically based on high clinical
      suspicion and a strongly positive tuberculin test.

PMID- 12236434
TI  - Social aspects of patients with pulmonary tuberculosis in Indonesia.
AB  - Tuberculosis (TB) patients have not only medical but also social problems related
      to their illness, which may influence their motivation for the completion of
      treatment. This study investigated the social aspects of patients with TB in an
      urban area of Jakarta, Indonesia. Most TB patients had poor nutritional status
      and lived in crowded environments. They faced joblessness and negative attitudes
      from their neighbors and relatives. A few of the patients were afraid that they
      would not find a partner; others said that their diseases impaired their
      marriages. We found that patients with a subnormal body mass index restricted
      their social contact with their family more than patients with a normal body mass
      index. In general, patients were supported by their families, both financially
      and socially. Our findings suggest that priority should be given to developing
      programs aimed at strengthening the family support of TB patients.

PMID- 12236435
TI  - Mycobacterium tuberculosis infection among HIV/AIDS patients in Thailand:
      clinical manifestations and outcomes.
AB  - A one year retrospective study, was conducted at Bamrasnaradura Hospital,
      Nonthaburi Province, Bangkok, Thailand, of 271 subjects with both TB and
      HIV/AIDS. Single males (median age group 31 to 40 years) were most likely to
      develop co-infection. The commonest clinical manifestations on initial
      presentation included a low grade fever, cough, weight loss, lymphadenopathy with
      pancytopenia, and lung infiltrates. Multi-drug resistant TB (MDR-TB) was found in
      26.6% of the subjects which was significantly associated with a past history of
      anti-TB treatment (p = 0.005; OR=2.5); it was also significantly associated with
      disseminated TB (p = 0.022; OR=1.9) and mortality (p= 0.013; OR=2.8). Analysis of
      clinical outcomes showed that 46.7% were lost to follow-up and 13.3% had died by
      the time of follow-up. Among those who survived, only 11.4% had been successfully
      treated; the rest had not improved due to relapse (2.9%), therapeutic failure
      (8.8%), treatment in progress (5.9%), and failure to complete treatment (10.7%).

PMID- 12236436
TI  - Clinical features of diphtheria in thai children: a historic perspective.
AB  - To study the clinical and laboratory features of childhood diphtheria, the cases
      of 381 children with clinical and bacteriological diagnoses of diphtheria who
      were treated at the Children's Hospital between 1976 and 1985 were reviewed. Of
      these, 191 were males and 190 were females. The mean age was 4.6 years.
      Approximately 75% of the patients had no history of immunization. Common
      manifestations of diphtheria included patch (100%), fever (92.4%), upper
      respiratory tract infection (91.6%), upper airway obstruction (42.3%), hoarseness
      (36.7%), and bull neck (11.3%). The mean duration of fever prior to admission was
      3.3 days with a range of 0-11 days. Patch sites included the tonsils (91.9%), the
      pharynx (55.9%), the larynx (27.8%) and others (24.4%). Complications included
      upper airway obstruction (42.3%), cardiac complications (10.0%) and neurological
      complications (4.7%). The mortality rate was 5.8%. There were significant
      associations between death and the presence of bull neck, laryngeal patch, airway
      obstruction and cardiac complications. Early recognition and prompt treatment
      will decrease complications and mortality in this group of patients.

PMID- 12236437
TI  - Clinical features of community-acquired pneumonia treated at Srinagarind
      Hospital, Khon Kaen, Thailand.
AB  - Pneumonia is a serious illness associated with significant morbidity and
      mortality. The interpretation guidelines for pneumonia management requires
      knowledge of both the clinical presentation of the disease and local
      epidemiology. We studied the clinical features, initial laboratory results,
      antibiotic sensitivities, and outcomes of patients diagnosed with acute community
      acquired pneumonia between January 1999 and December 2000 at Srinagarind
      Hospital. The causative organisms were identified in only 52.2% patients;
      Streptococcus pneumoniae accounted for 23.1% of infections. Other common causes
      included Klebsiellapneumoniae (19.2%), Burkholderia pseudomallei (15.4%),
      Hemophilus influenzae (11.5%), Mycoplasma pneumoniae (6.2%), and Staphylococcus
      aureus (4.6%). Younger patients were more likely to be infected with M.
      pneumoniae, while the mean age of those with other types of infections was 50.
      Healthy adults were infected with M. pneumoniae and S. pneumoniae; specific
      pathogens attacked patients with certain co-morbidity : i) diabetes mellitus and
      ageing, ii) diabetes mellitus and renal disease, iii) cardiovascular diseases,
      and iv) connective tissue diseases and steroid-use; these patients were
      vulnerable to i) K. pneumoniae, ii) B. pseudomallei, iii) H. influenzae, and iv)
      S. aureus respectively. White blood cell counts were normal in M. pneumoniae
      infection. Gram-stained sputum had some limitations, especially when determining
      Gram-negative infections; chest x-rays could not differentiate pathogens.
      Bactermia was found in one half of patients infected with B. pseudomallei and S.
      aureus. Antibiotic-resistant organisms were not common in our study. Because
      morbidity and mortality were high among patients infected with S. aureus and B.
      pseudomallei, empirical antibiotic treatment should be considered in suspected
      cases, especially when patients present with acute severe community-acquired
      pneumonia.

PMID- 12236438
TI  - Oculosporidiosis in eastern Nepal: a report of five cases.
AB  - Rhinosporidiosis is endemic in India, Sri Lanka, and parts of East Africa and
      South America; sporadic cases are reported in other countries. We report on five
      patients from eastern Nepal with oculosporidiosis. The conjunctiva was involved
      in two patients and the lacrimal sac was involved in three patients; treatment
      was by simple total excision of the conjunctivalgrowth (patients with
      conjunctival involvement) and by dacryocystectomy (patients with lacrimal sac
      involvement). This is the second case report from Nepal.

PMID- 12236439
TI  - Analysis of the reg1alpha and reg1beta gene transcripts in patients with
      fibrocalculous pancreatopathy.
AB  - Fibrocalculous pancreatopathy is a form of diabetes, associated with tropical
      chronic calcific pancreatitis, in which islet beta-cell loss and pancreatic stone
      formation are found. It is likely to be a multifactorial disease with both
      genetic and environmental components. Regenerating (reg) gene encodes protein
      that has been involved in pancreatic lithogenesis and the regeneration of islet
      cells and therefore the abnormality of reg genes could be associated with
      fibrocalculous pancreatopathy. In this study, regla and reg1beta mRNAs were
      isolated from peripheral blood lymphocytes obtained from 16 patients with
      fibrocalculous pancreatopathy, 42 patients with type 1 diabetes, 37 patients with
      type 2 diabetes, and 22 normal controls. mRNAs were amplified by reverse
      transcription polymerase chain reaction (RT-PCR) and analysed by a single strand
      conformation polymorphism (SSCP) technique. The reg1alpha and reg1beta mRNAs were
      isolated, indicating the ectopic expression of these genes in peripheral blood
      lymphocytes; however, variation among mobility patterns was not observed in the
      SSCP analysis of the RT-PCR products. The results indicated that there was no
      abnormality of the regla and reg1beta mRNAs obtained from the study groups.

PMID- 12236440
TI  - Anemia in remote interior communities in Sarawak, Malaysia.
AB  - A cross-sectional survey of 365 individuals, (51.9% males, 48.1% females; ages 5
      85 years), from five remote interior communities in upper Rejang River basin
      Sarawak, Malaysia, found 24.4% were anemic. The range and mean of Hb
      concentration in male and female were: 7.2-17.0 mg/ml and 13.7 mg/ml and 7.9-15.7
      mg/ml and 12.9 mg/ml respectively. Amongst the five tribes surveyed, the
      prevalence of anemia (range: 10.6-46.7%), was higher among the Penans (46.7%),
      Kenyahs (31.1%), Kajangs (27.8%) and Kayans (19.3%), than amongst the Ukits
      (10.6%). Anemia is more common among males >40 years and among adolescents and
      young reproductive females, as well as elderly females > 61 years old. Of the 83
      anemic individuals, 6.0% and 3.6% had Trichuris trichiura or hookworm
      respectively; however there is no clear association with intestinal worm
      infection.

PMID- 12236441
TI  - The effects of rehydration on cycling performance after exercise-induced
      dehydration.
AB  - The effects of 7.6% carbohydrate-electrolyte solution (CES) and placebos (P) on
      rehydration (R) after exercise-induced dehydration and on a subsequent time-trial
      (TT) of cycling performance were studied. Thirteen male subjects exercised in a
      thermally-controlled environment (28 degrees C, 63% RH) until 3% of their body
      weight was lost. After exercise, the subjects moved to a neutral environment (22
      degrees C) and rested for 30 minutes prior to a 2-hour R period. During R,
      subjects were fed CES or P to a maximum volume of 120% of previous body mass loss
      at 0, 30, and 60 minutes, in bolus-doses of 50%, 40% and 30% respectively. After
      R, subjects performed a 1-hour TT with no further fluid intake. % R with CES was
      significantly higher than with P (70 +/- 3% vs 60 +/- 5%; p < 0.01). During the
      TT, blood glucose dropped in the CES group but not in the P group. It was found
      that, despite a more effective R with CES, the performance results did not differ
      between groups (65.1 +/- 2.2 minutes and 65.2 +/- 2.3 minutes for CES and P
      respectively). It is suggested that an insulin-mediated rebound effect on CHO
      metabolism during TT, in which no further CHO was supplied, nullified the
      benefits of rehydration.

PMID- 12236442
TI  - Associations of particulate matter and daily mortality in Bangkok, Thailand.
AB  - The association between airborne particles and daily mortality has been reported
      in many locations, but mainly in western countries. There is a need to
      investigate the association in locations where the emission sources, weather, and
      other environmental conditions differ from those in western countries. In this
      study, the acute effects of PM10 and visibility on daily mortality in Bangkok,
      Thailand, from 1992 to 1997, were examined. A Poisson regression model was
      developed to estimate the excess daily mortality associated with PM10 and
      visibility, while controlling for long-term trends, season, and variations in
      weather. It was found that increasing PM10 and decreasing visibility levels were
      independently associated with increasing daily mortality from all non-external
      causes, cardiovascular, respiratory, and other diseases. The observed
      associations were stronger for respiratory diseases than for cardiovascular and
      other diseases and were stronger for persons aged > or = 65 years than for those
      in the younger age group. The results of the PM10/mortality and
      visibility/mortality models were consistent, suggesting that visibility may be
      considered as a surrogate marker for the assessment of the adverse health effects
      of fine particulate matter when data from direct gravimetric measurements are not
      available.

PMID- 12236444
TI  - Sociodemographic characteristics of food handlers and their knowledge, attitude
      and practice towards food sanitation: a preliminary report.
AB  - Diseases spread through food still remain a common and persistent problems
      resulting in appreciable morbidity and occasional mortality. Food handlers play
      an important role in ensuring food safety throughout the chain of production,
      processing, storage and preparation. This study is to explore the pattern of
      sociodemographic distribution and to determine knowledge, attitude and practice
      of food handlers towards food-borne diseases and food safety. A total of 430 food
      handlers were randomly selected from Kota Bharu district and interviewed by using
      structured questionnaire. Distribution of food handlers was Malays (98.8%),
      females (69.5%), married (81.4%), working in food stalls (64.2%), involved in
      operational areas (49.3%), having no license (54.2%) and immunized with Ty2
      (60.7%). The mean age was 41 +/- 12 years and the mean income was RM 465 +/-
      243/month. The educational level was found as no formal education (10.5%),
      primary school (31.9%), secondary school (57.0%) and diploma/degree holders
      (0.7%). A significant number of food handlers (57.2%) had no certificate in food
      handlers training program and 61.9% had undergone routine medical examinations
      (RME). Almost half (48.4%) had poor knowledge. Multiple logistic regression
      showed type of premise [Odd ratio (OR) = 4.0, 95% Confidence interval (CI) =1.8
      7.5, p = 0.0004], educational level (OR = 4.0, 95% CI = 1.8-7.4, p = 0.0003) and
      job status of food handlers (OR = 0.5, 95% CI = 0.3-0.8, p = 0.0031)
      significantly influenced the level score of knowledge. No significant difference
      of attitude and practice between trained and untrained food handlers. Findings of
      this preliminary study may help in planning health education intervention
      programs for food handlers in order to have improvement in knowledge, attitude
      and practice towards food-borne diseases and food safety. Furthermore, it will in
      turn reduce national morbidity and mortality of food-borne diseases.

PMID- 12236443
TI  - Situation analysis of occupational and environmental health laboratory
      accreditation in Thailand.
AB  - The objective of this study was to analyze the current situation of laboratory
      accreditation (LA) in Thailand, especially on occupational and environmental
      health. The study integrated both quantitative and qualitative approaches. The
      response rate of the quantitative questionnaires was 54.5% (226/415). The
      majority of the responders was environmental laboratories located outside
      hospital and did not have proficiency testing. The majority used ISO 9000,
      ISO/IEC 17025 or ISO/ EEC Guide 25, and hospital accreditation (HA) as their
      quality system. However, only 30 laboratories were currently accredited by one of
      these systems. Qualitative research revealed that international standard for
      laboratory accreditation for both testing laboratory and calibration laboratory
      was ISO/IEC Guide 25, which has been currently revised to be ISO/IEC 17025. The
      National Accreditation Council (NAC) has authorized 2 organizations as
      Accreditation Bodies (ABs) for LA: Thai Industrial Standards Institute, Ministry
      of Industry, and Bureau of Laboratory Quality Standards, Department of Medical
      Sciences, Ministry of Public Health. Regarding LA in HA, HA considered clinical
      laboratory as only 1 of 31 items for accreditation. Obtaining HA might satisfy
      the hospital director and his management team, and hence might actually be one of
      the obstacles for the hospital to further improve their laboratory quality system
      and apply for ISO/IEC 17025 which was more technically oriented. On the other
      hand, HA may be viewed as a good start or even a pre-requisite for laboratories
      in the hospitals to further improve their quality towards ISO/IEC 17025.
      Interviewing the director of NAC and some key men in some large laboratories
      revealed several major problems of Thailand's LA. Both Thai Industrial Standards
      Institute and Bureau of Laboratory Quality Standards did not yet obtain Mutual
      Recognition Agreement (MRA) with other international ABs. Several governmental
      bodies had their own standards and accreditation systems, and did not accept
      other bodies' standards and systems. This put a burden to private laboratories
      because they had to apply and get accredited from several governmental bodies,
      but still had to apply and get accredited from international ABs especially for
      those dealing with exports. There were only few calibration laboratories, not
      enough for supporting the calibration required for the equipment in testing
      laboratories' LA. Purchasing proficiency testing specimens from abroad was very
      expensive, and often got into troubles with the customs duty procedures. The
      authors recommend some strategies and activities to improve laboratory
      accreditation in Thailand. Improvement in occupational and environmental health
      laboratories would essentially be beneficial to laboratory accreditation of other
      areas such as clinical laboratory.

PMID- 12236445
TI  - Rational drug use in Cambodia: study of three pilot health centers in Kampong
      Thom Province.
AB  - This study obtained baseline information for the design of a strategy to address
      irrational prescribing practices in three health centers in Kampong Thom
      Province, Cambodia. Indicators of rational drug use have been measured and
      compared with Standard Guidelines. Data were collected from patients' registers
      and by interviewing patients immediately after patient-prescriber and patient
      dispenser encounters. Checklists and pre-designed forms were used to collect data
      regarding the World Health Organization drug use indicators and some additional
      indices. Of the 330 prescriptions analyzed, the results showed that the average
      number of drugs per prescription was 2.35 and that a large proportion of the
      prescriptions contained two or more drugs that could result in adverse drug
      interactions. Prescribing by generic names (99.8%) was encouraging. The exposure
      of patients to antibiotics (66% to 100%) was high, and injection use (2.4%) was
      often unnecessary. Prescribing from the Essential Drugs List (99.7%) was
      satisfactory. The average consultation and dispensing times were short and not
      sufficient for patients to get health information. All the prescribed drugs were
      supplied, but all were inadequately labeled. Some 55% of patients knew the
      correct dosage of their drugs. The availability of key essential drugs (86.6%)
      was below the Standard. The percentages of appropriate prescriptions for treating
      malaria, diarrhea and acute respiratory infection treatment were 68.3%, 3.3%, and
      45%, respectively. Inappropriate prescriptions were mostly due to unsuitable
      dosages, incorrect drugs, and the improper duration of treatment. The results
      suggest a need for intervention to curb the irrational use of drugs in
      prescribing at the three pilot health centers. Continuing education of
      prescribers and healthcare providers, monitoring, supervision, public education
      would be beneficial.

PMID- 12236446
TI  - Hypertension in public health.
AB  - Re-emerging epidemic of cardiovascular diseases activates each country to develop
      its strategies in primary prevention. Hypertension, as a leading cause, is a
      challenging public health problem. Awareness, treatment and control of
      hypertension are still inadequate. Socioeconomic factors may be the obstacles.
      Educating and motivating both the physicians and patients could provide some
      solutions. Therefore, national projects of screening, setting targets and
      community participation have to be launched throughout each area. With active
      public health prevention and lifestyle modifications, one can hope to decrease
      both hypertensive prevalence and its complication risks in the near future.

PMID- 12236447
TI  - Web-based telerehabilitation for the upper extremity after stroke.
AB  - Stroke is a leading cause of disability in the United States and yet little
      technology is currently available for individuals with stroke to practice and
      monitor rehabilitation therapy on their own. This paper provides a detailed
      design description of a telerehabilitation system for arm and hand therapy
      following stroke. The system consists of a Web-based library of status tests,
      therapy games, and progress charts, and can be used with a variety of input
      devices, including a low-cost force-feedback joystick capable of assisting or
      resisting in movement. Data from home-based usage by a chronic stroke subject are
      presented that demonstrate the feasibility of using the system to direct a
      therapy program, mechanically assist in movement, and track improvements in
      movement ability.

PMID- 12236448
TI  - The influence of weight and starting height on lifting mechanics in lower
      extremity amputees.
AB  - This study compares the lifting mechanics of lower extremity amputees to controls
      and describes the influence of weight lifted and starting height on lifting
      style. Subjects included three individuals with transtibial amputation (TTA), two
      individuals with transfemoral amputation (TFA), and three able-bodied controls
      (CO). Amputee subjects performed six repetitions of six weights, randomly
      ordered, from two starting heights. TTA lifted from 30 cm and knee height, TFA
      from knee and thigh height, and controls from all three heights. Data were
      obtained from a work simulator, force plate, and a motion analysis system, with
      starting posture index, lateral sway index, lift duration, synchrony index, and
      hip moments and elbow moments as dependent measures. The results for each lifting
      height were analyzed using a mixed model repeated measures MANOVA to test for
      group and weight differences and post hoc tests were applied when appropriate.
      Results suggest that healthy lower extremity amputees who have had a number of
      years to adjust to their prosthesis and develop compensatory strategies can
      complete a repetitive lifting task at a performance level very similar to able
      bodied controls. The most consistent group differences detected were in the
      timing parameters: synchrony and duration. TTA and TFA tended to lift with less
      synchronization of hip and knee movements than able-bodied controls and to
      initiate the lift with their upper bodies. In contrast, able-bodied controls
      tended to move their upper and lower bodies more synchronously during the lift.
      TTA had longer lift durations than CO. In terms of stability and moments
      generated, TTA lifted very similarly to controls. TFA used a different lifting
      style that involved higher moments and more use of the upper body, particularly
      for lifts of heavier weights. TFA appeared to be less stable than CO, while TTA
      did not appear to be less stable than CO.

PMID- 12236449
TI  - The Hephaestus Smart Wheelchair System.
AB  - The Hephaestus Smart Wheelchair System is envisioned as a series of components
      that clinicians and wheelchair manufacturers will be able to attach to standard
      power wheelchairs to convert them into "smart wheelchairs." A prototype of the
      system has been developed and mounted on an Everest and Jennings Lancer2000
      wheelchair. The prototype bases its navigation assistance behavior on the
      behavior developed for the NavChair Assistive Wheelchair Navigation System, but
      the underlying hardware and software are being designed to facilitate
      commercialization. This paper describes our design goals for the Hephaestus
      system and discusses the current status of the system prototype as well as plans
      for future work.

PMID- 12236450
TI  - Voice control of a powered wheelchair.
AB  - Several researchers have described voice control mechanisms for a power
      wheelchair, but voice control has yet to become a commercially viable control
      alternative. One problem with voice control is that the voice's limited bandwidth
      renders it impossible to make frequent small adjustments to the wheelchair's
      velocity. One possible solution is to utilize voice control in combination with
      the navigation assistance provided by "smart wheelchairs," which use sensors to
      identify and avoid obstacles in the wheelchair's path. This paper describes an
      experiment that compares the performance of able-bodied subjects using voice
      control to operate a power wheelchair both with and without navigation
      assistance.

PMID- 12236451
TI  - The optimal stimulation pattern for skeletal muscle is dependent on muscle
      length.
AB  - Stimulation patterns can be optimized by maximizing the force-time integral (FTI)
      per stimulation pulse of the elicited muscle contraction. Such patterns,
      providing the desired force output with the minimum number of pulses, may reduce
      muscle fatigue, which has been shown to correlate to the number of pulses
      delivered. Applications of electrical stimulation to use muscle as a controllable
      biological actuator may, therefore, be improved. Although muscle operates over a
      range of lengths, optimized patterns have been determined only at optimal muscle
      length. In this study, the patterns with up to four pulses that produced the
      highest isometric FTI were determined at 10 muscle lengths for 11 rabbit tibialis
      anterior muscles. The interpulse intervals (IPIs) used ranged from 4 to 54 ms. At
      high muscle length, the optimal stimulation pattern consisted of an initial short
      IPI (doublet) followed by longer IPIs, in agreement with previous studies.
      However, at low length, the third pulse still elicited more than linear summation
      (triplet); furthermore, the relative enhancement of the FTI per pulse was
      considerably larger at low length than at high length, suggesting that optimal
      stimulation patterns are length dependent.

PMID- 12236452
TI  - Evaluation of command algorithms for control of upper-extremity neural
      prostheses.
AB  - Five new command control algorithms were created to enable increased control over
      grasp force in upper-extremity neural prostheses. Most of these algorithms took
      advantage of the ability to lock or assign a steady command value to the hand
      neural prosthesis. Five able-bodied subjects tested the algorithms by using a
      shoulder controller that controlled a video-simulated hand to repeatedly complete
      a consistent evaluation task. A generalized estimating equations-based linear
      model was used to analyze the data. The algorithms were ranked via contrast
      analyses between the coefficient values from the linear model of the proportional
      control with lock algorithm, which is the algorithm presently used in neural
      prostheses, and each of the other algorithms. The algorithms that allowed
      adjustment of the command value after the hand was locked as well as algorithms
      that allowed a decrease in controller gain after the hand was locked performed
      better than the proportional control with lock algorithm. Algorithms that changed
      command as a function of time performed worse than the proportional control with
      lock algorithm. Further, the computer-based video simulator proved to be useful
      as a first-pass evaluation tool for neural prosthesis control.

PMID- 12236453
TI  - A comparison of the mediational properties of four adolescent smoking expectancy
      measures.
AB  - This prospective study compared the ability of 4 smoking expectancy measures to
      mediate the influence of peer, parent, and current smoking on adolescents'
      cigarette use 3 months later. No evidence for mediation was found when
      expectancies were operationalized as unidimensional subjective expected utility
      (SEU), multidimensional SEU, or unidimensional SEU decomposed into probability
      and desirability main effects and their interaction. Evidence for partial
      mediation was found for the decomposed multidimensional SEU measure. The results
      suggest that (a) peer and current cigarette use may influence future smoking
      indirectly through adolescents' probability estimates that smoking will control
      negative emotions and (b) the relationship between current and future smoking
      also may be mediated by adolescents' beliefs about the desirability of weight
      control.

PMID- 12236454
TI  - Relations between self-generated positive and negative expected smoking outcomes
      and smoking behavior: an exploratory study among adolescents.
AB  - The expected outcomes of drug use figure prominently in models of drug
      motivation. This report presents the relations between self-generated expected
      outcomes of smoking and smoking behavior in 674 adolescents. Expected outcomes of
      smoking were related to current smoking, experimentation, and susceptibility
      among never-smokers, even after controlling for key correlates of smoking
      behavior, including gender, grade, ethnicity, and peer smoking. Although more
      negative than positive smoking outcomes were accessible from memory, more
      positive than negative expected outcomes were correlated with smoking behavior.
      Both the content and number of self-generated expected outcomes provided unique
      associative information. In sum, greater elaboration of smoking-related memory
      networks, as well as the specific content of those networks, appear to be
      associated with smoking behavior.

PMID- 12236455
TI  - Reactivity to ecological momentary assessment: an example using undergraduate
      problem drinkers.
AB  - A. A. Stone and S. Shiffman (1994) defined ecological momentary assessment (EMA)
      as monitoring or sampling strategies that assess phenomena at the moment they
      occur in natural settings, thus maximizing ecological validity while avoiding
      retrospective recall. To address the extent to which EMA affects the behaviors
      and cognitions under observation, the authors examined behavioral and
      motivational reactivity to EMA among male and female undergraduate problem
      drinkers (n = 33). Participants completed a 2-week monitoring protocol using
      palmtop computers as well as pre- and postmonitoring measures of their drinking
      behavior and motivation for change. The findings suggest that the magnitude of
      reactivity to EMA is small. Suggestions for future research are presented.

PMID- 12236456
TI  - The theory of reasoned action as a model of marijuana use: tests of implicit
      assumptions and applicability to high-risk young women.
AB  - The theory of reasoned action (TRA) is used to model decisions about substance
      use among young mothers who became premaritally pregnant at age 17 or younger.
      The results of structural equation modeling to test the TRA indicated that most
      relationships specified by the model were significant and in the predicted
      direction. Attitude was a stronger predictor of intention than norm, but both
      were significantly related to intention, and intention was related to actual
      marijuana use 6 months later. Outcome beliefs were bidimensional, and positive
      outcome beliefs, but not negative beliefs, were significantly related to
      attitude. Prior marijuana use was only partially mediated by the TRA variables;
      it also was directly related to intentions to use marijuana and to subsequent
      use.

PMID- 12236457
TI  - Relation of depression diagnoses to 2-year outcomes in cocaine-dependent patients
      in a randomized continuing care study.
AB  - This study examined the relation between depression diagnoses and outcomes in 132
      cocaine-dependent patients who were randomized to relapse prevention (RP) or
      standard 12-step focused group continuing care and followed for 2 years.
      Depressed patients attended more treatment sessions and had more cocaine-free
      urines during treatment than participants without depression, but they drank
      alcohol more frequently before treatment and during the 18-month posttreatment
      follow-up. Cocaine outcomes in depressed patients deteriorated to a greater
      degree after treatment than did cocaine outcomes in patients without depression,
      particularly in patients in RP who had a current depressive disorder at baseline.
      The best alcohol outcomes were obtained in nondepressed patients who received RP.
      The results suggest that extended continuing care treatment may be warranted for
      cocaine-dependent patients with co-occurring depressive disorders.

PMID- 12236458
TI  - Use of survival analyses to examine onset and staging of DSM-IV alcohol symptoms
      in women.
AB  - Despite their implications for diagnostic validity, few studies have examined
      patterns of alcohol symptom onset in women. Using Structured Clinical Interview
      for the DSM-IV (M. B. First, M. Gibbon, R. L. Spitzer, & J. B. W. Williams, 1995)
      data, the authors applied survival analysis to Diagnostic and Statistical Manual
      of Mental Disorders (4th ed.; American Psychiatric Association, 1994) alcohol
      symptoms in 87 women in treatment. Legal problems occurred rarely and did not fit
      a staging model. Compared with men previously studied, women showed a later onset
      of symptoms, which developed in 4 stages: abuse, consequation, accommodation to
      the illness, and physiological dependence. Three symptoms-hazardous use,
      larger/longer use than intended, and lots of time spent using--occurred early and
      may be useful for screening purposes.

PMID- 12236459
TI  - Problem drinking and the workplace: an individualized approach to prevention.
AB  - The present study evaluated the efficacy of a brief, individualized, alcohol
      abuse prevention program designed to reduce problem drinking within the workplace
      environment. One hundred fifty-five randomly selected employees of a medium-sized
      company in the food and retail services sector participated in a 6-month
      controlled worksite prevention trial. Female problem drinkers who received the
      intervention were more likely than those in the no-treatment control group to
      reduce alcohol-related negative consequences at follow-up. In addition, there was
      a significant multivariate treatment effect, suggesting that participants who
      received the intervention were significantly more likely to reduce drinking
      frequency at follow-up. Evaluation of attrition rates and reports of participant
      satisfaction suggest that the intervention was effective in engaging participants
      at all levels of alcohol consumption.

PMID- 12236460
TI  - Binge drinking in later life: comparing young-old and old-old social drinkers.
AB  - Although widespread binge drinking has been documented in younger groups, few
      studies have examined this behavior among older individuals. We assessed
      differences in bingeing between young-old (n = 189) and old-old (n = 137) social
      drinkers. Of those who reported drinking, no significant age o rgender
      differences were uncovered in alcohol consumption (M = 6.6, SD = 9.4) or degree
      of alcohol-related problems (M = 12.2, SD = 3.1). Logistic regression analysis
      showed that old-old adults were 15.7 times less likely to binge drink than the
      young-old; older women overall were 19.7 times less likely to binge relative to
      older men. Also, correlations were more diverse among old-old adults. The need
      for better understanding of bingeing among elders is discussed.

PMID- 12236461
TI  - Varying results for immunoassay screening kits for cotinine level.
AB  - Our earlier study found that although enzyme-linked immunosorbent analysis
      (ELISA) screening assays for urine cotinine indicated use in former smoking
      treatment patients who reported abstinence, this finding was sometimes incorrect
      when validated against gas chromatography/mass spectrometry (GC/ MS; P. Gariti,
      A. I. Alterman, R. Ehrmann, F. D. Mulvaney, & C. P. O'Brien, 2002). In the
      current validation study, separate urine samples of 71 of these same patients
      were reanalyzed by an independent laboratory in blinded fashion using a screening
      enzyme immunoassay (EIA) analysis and GC/MS confirmation. EIA results showed
      almost total agreement with confirmatory testing. The findings indicate that use
      of screening ELISA/EIA for urine cotinine can detect unreported cases of smoking
      in former patients, but that care is needed in selecting a laboratory for
      conducting these tests.

PMID- 12236462
TI  - Use of the fagerstrom tolerance questionnaire for measuring nicotine dependence
      among adolescent smokers in China: a pilot test.
AB  - The validity of the Prokhorov adolescent version of the Fagerstrom Tolerance
      Questionnaire (FTQ) has not been demonstrated in assessing nicotine dependence
      among Chinese adolescents in China. Data for 48 tenth-grader 30-day smokers in
      Wuhan, China (ages 16-17 years), were analyzed. Two different item scoring
      protocols were used, and self-reports of smoking were validated with saliva
      cotinine. When items were scored using Protocol A, Cronbach's alphas were .42 and
      .63 for the 7-item and the 4-item scales, respectively; while using Protocol B,
      the alphas were .67 and .79 for the 7-item and 4-item scales, respectively. The
      total FTQ scores were significantly associated with self-reported smoking and
      saliva cotinine levels. These results support the reliability and validity of the
      Prokhorov FTQ.

PMID- 12236463
TI  - Depressive symptoms and readiness to quit smoking among cigarette smokers in
      outpatient alcohol treatment.
AB  - The authors examined whether length of alcohol abstinence and depressive symptoms
      were related to motivational readiness to consider smoking cessation among
      patients in alcohol treatment. Participants were adults (N = 253) enrolled in a
      smoking cessation trial. Controlling for gender, depressive symptoms, and
      nicotine dependence, hierarchical regression analysis of readiness scores
      revealed a significant interaction of days since last drink and depressive
      symptoms. It was found that a greater number of days since last drink was
      associated with greater readiness, but only among patients with low scores on the
      Center for Epidemiologic Studies Depression Scale (L. S. Radloff, 1977). The
      findings suggest that alcoholic smokers with low depressive symptoms are more
      receptive to quitting smoking after sustained alcohol abstinence.

PMID- 12236464
TI  - Couple communication and female problem drinking: a behavioral observation study.
AB  - Couples with alcohol and relationship problems often report poor communication,
      yet little is known about the communication of maritally distressed couples in
      which the woman abuses alcohol (MDWA couples). Compared with maritally distressed
      couples without alcohol problems (MDNA) and couples with neither problem (NDNA),
      MDWA couples showed a distinctive pattern of negative communication. Similar to
      MDNA men, MDWA men spoke negatively to their partners but listened positively to
      their partners much like NDNA men. MDWA women listened negatively, much as MDNA
      women did, but spoke positively, like NDNA women did. The interactions of MDWA
      couples can be characterized as a male-demand-female-withdraw pattern, which is a
      gender reversal of the female-demand-male-withdraw pattern often observed in MDNA
      couples.

PMID- 12236465
TI  - Transcription in the archaea: basal factors, regulation, and stress gene
      expression.
AB  - A brief survey is presented of salient findings on transcription in the Archaea,
      focussing on stress genes of the hsp70(dnaK) locus, which code for the molecular
      chaperones Hsp70(DnaK), Hsp40(DnaJ), and GrpE. Archaeal basal factors and some
      recently characterized regulators pertinent to non-stress genes are presented
      first to show their similarities and differences with equivalents in organisms of
      the other two phylogenetic domains, Bacteria and Eucarya, and to reveal clues on
      how these or similar factors might transcribe and regulate the archaeal stress
      genes. The second part of the article deals with the hsp70(dnaK)-locus genes,
      particularly those from Methanosarcina mazeii, because they are virtually the
      only ones within the methanogenic Archaea whose patterns of constitutive and
      stress-induced expressions have been studied. Therefore, these genes, provide a
      standardized model system to elucidate transcription initiation and regulation at
      the molecular level in this phylogenetic group. Promoters, and other cis-acting
      sites that are, or might be, involved in stress-gene expression are described.
      Conformational changes of basal transcription factors after interaction with
      stress-gene promoters are discussed that suggest ways for generating a large
      diversity of initiation complexes using a few factors and DNA sites in different
      combinations. Likewise, the effects of stress on DNA topology and on TBP-TFB
      promoter complex formation and tightness are described, which might also
      contribute to the generation of transcription-initiation complex diversity. This
      diversity would be key to differential gene expression, namely, which genes are
      transcribed, when (basal, steady expression vs. sporadic stress-induced
      expression), and to what level. Future research should investigate this
      diversity, and the mechanism of complex formation and action at the atomic,
      molecular, and supramolecular levels to elucidate the dynamics of transcription
      initiation in real time.

PMID- 12236466
TI  - Effects of consumption of probiotics and prebiotics on serum lipid levels in
      humans.
AB  - The objective of this article is to review existing studies concerning the
      effects of probiotics and prebiotics on serum cholesterol concentrations, with
      particular attention on the possible mechanisms of their action. Although not
      without exception, results from animal and human studies suggest a moderate
      cholesterol-lowering action of dairy products fermented with appropriate
      strain(s) of lactic acid bacteria and bifidobacteria. Mechanistically, probiotic
      bacteria ferment food-derived indigestible carbohydrates to produce short-chain
      fatty acids in the gut, which can then cause a decrease in the systemic levels of
      blood lipids by inhibiting hepatic cholesterol synthesis and/or redistributing
      cholesterol from plasma to the liver. Furthermore, some bacteria may interfere
      with cholesterol absorption from the gut by deconjugating bile salts and
      therefore affecting the metabolism of cholesterol, or by directly assimilating
      cholesterol. For prebiotic substances, the majority of studies have been done
      with the fructooligosaccharides inulin and oligofructose, and although convincing
      lipid-lowering effects have been observed in animals, high dose levels had to be
      used. Reports in humans are few in number. In studies conducted in normal
      lipidemic subjects, two reported no effect of inulin or oligofructose on serum
      lipids, whereas two others reported a significant reduction in serum
      triglycerides (19 and 27%, respectively) with more modest changes in serum total
      and LDL cholesterol. At present, data suggest that in hyperlipidemic subjects,
      any effects that do occur result primarily in reductions in cholesterol, whereas
      in normal lipidemic subjects, effects on serum triglycerides are the dominant
      feature.

PMID- 12236467
TI  - Jewish-Arab violence: perspectives of a dominant majority and a subordinate
      minority.
AB  - In 2 studies, the authors investigated intergroup violence as perceived by
      Israeli Jews and Israeli Arabs. University and junior high school students judged
      Jewish-Arab clashes, which ended in shots fired at a crowd of either Jewish or
      Arab demonstrators. The authors hypothesized that judgments of these shootings
      would be contingent on 3 variables: the origin of the respondent, the origin of
      the shooter, and the level of danger to the shooter. The results tended to
      support those hypotheses: (a) Both Jewish and Arab respondents justified
      shootings by members of their own group more readily than those by members of the
      other group. (b) Jewish judgments of violence were associated more closely than
      Arab judgments with the danger that the demonstrators posed to the shooter. (c)
      The Jewish respondents referred to self-defense more often than did the Arab
      respondents to justify their judgments, whereas the Arab respondents referred
      more often to intergroup considerations. Those differences may reflect the
      disagreement between the majority and the minority on the issue that each group
      should take into consideration in cases of international violence.

PMID- 12236468
TI  - Conflict resolution and peer mediation in middle schools: extending the process
      and outcome knowledge base.
AB  - Many professional educators are implementing school-based prevention focused on
      conflict resolution (CR) and peer mediation (PM). The authors conducted research
      on CR-PM in 3 middle schools. Specifically, they surveyed teachers and students,
      tracked disciplinary incidents across school years, collected mediation data, and
      compared mediators with a matched sample to determine attitudinal change as a
      result of PM training and experience. The authors also surveyed peer mediators
      and disputants about program satisfaction, as well as peer mediators and their
      parents about the generalization of PM skills. The authors conclude with
      implications for developing future CR programs, including a focus on mediation
      process evaluation as well as schoolwide outcome measures and the use of peer
      mediation training as an intervention for students at risk.

PMID- 12236469
TI  - Racial bias in decisions made by mock jurors evaluating a case of sexual
      harassment.
AB  - White (N = 161) and Black (N = 152) college students served as mock jurors in a
      simulated civil case in which a female plaintiff accused a male defendant of
      sexual harassment. The authors experimentally manipulated the race (Black or
      White) of the litigants and asked the mock jurors to decide whether the defendant
      was guilty; to rate the certainty of their belief in the defendant's guilt; and,
      when they judged the defendant guilty, to recommend an award to the plaintiff.
      Mock jurors of both races tended to favor litigants of their own race and their
      own gender. Racial bias was highest among White male jurors and lowest among
      White female jurors.

PMID- 12236470
TI  - A field examination of two measures of work motivation as predictors of leaders'
      influence tactics.
AB  - The authors tested 2 motivation measures, the Motivation Sources Inventory (MSI;
      J. E. Barbuto & R. W. Scholl, 1998) and the Job Choice Decision-Making Exercise
      (A. M. Harrell & M. J. Stahl, 1981) as predictors of leaders' influence tactics.
      The authors sampled 219 leader-member dyads from a variety of organizations and
      communities throughout the central United States. Results strongly favored the
      MSI as a predictor of influence tactics. Limitations of the study include low
      power of relationships, sample size as limited by the research design, and
      education levels of participants. Future researchers should use larger and more
      diverse samples and test other relevant antecedents of leaders' behaviors.

PMID- 12236471
TI  - Attitudes toward U.S. immigration policy: the roles of in-group-out-group bias,
      economic concern, and obedience to law.
AB  - California's Proposition 187, directed primarily toward Mexican immigrants,
      deprives illegal immigrants of many benefits associated with U.S. citizenship and
      facilitates their deportation. The authors hypothesized that the respondents'
      opinions on this proposition would be determined by in-group-out-group bias
      (i.e., the tendency to evaluate the ethnic out-group more negatively than the
      ethnic in-group). In accord with that hypothesis, variations in respondent
      ethnicity (Studies 1 and 2) and in immigrant ethnicity (Study 3) were
      systematically related to the respondents' opinion on that issue. Moreover, the
      effect of in-group-out-group bias was independent of perceived reasoned economic
      and legal considerations that underlay the respondents' opinion.

PMID- 12236472
TI  - To work or not to work: nonfinancial employment commitment and the social
      desirability bias.
AB  - The so-called "lottery question," which asks whether individuals would stop or
      continue working if there were no economic reasons to do so, was used to evaluate
      non-financial employment commitment. Data were collected through a survey
      conducted among a representative sample of the adult population in Israel. The
      sample included 501 respondents, who were interviewed via telephone in their
      homes by professional interviewers from a national survey agency. The additional
      contribution of social desirability to the prediction of nonfinancial employment
      commitment, beyond the contribution of age, is significant. There is a higher
      likelihood of indicating a desire to continue working under conditions of high
      social desirability rather than under those of low social desirability. It is
      suggested that, in order to examine the actual scope of nonfinancial employment
      commitment, some measures of detecting or reducing the social desirability bias
      should be taken.

PMID- 12236473
TI  - Work-family conflict, locus of control, and women's well-being: tests of
      alternative pathways.
AB  - The author tested for the 3 possible pathways (i.e., direct, moderator, and
      mediator effects) in which locus of control can influence the relationship
      between work-family conflict and well-being. The author predicted that work
      family conflict would be negatively correlated with well-being. In a sample of
      310 Malaysian employed women with families, work-family conflict was a
      significant predictor of both job satisfaction and distress--negatively related
      to job satisfaction and positively related to symptoms of distress. More
      important, the results provided support for the effects of all 3 pathways of
      control on the relationship between work-family conflict and well-being,
      depending on the outcome measure: For job satisfaction, locus of control had
      direct effects, acted as a partial mediator, and played a significant moderating
      role. In contrast, only the direct effect of locus of control predicted distress.
      The author discusses those findings with reference to the literature on work
      family conflict, locus of control, and the issue of stress-distress specificity.

PMID- 12236474
TI  - Forgiveness of self and others and emotional empathy.

PMID- 12236475
TI  - Racism in rape trials.

PMID- 12236476
TI  - The use of hand gestures and smiles in the inaugural addresses of presidents of
      the United States.

PMID- 12236477
TI  - Proton pump inhibitors--differences emerge in hepatic metabolism.
AB  - Differences are emerging with respect to the mode of metabolism of proton pump
      inhibitors. All, except rabeprazole, are metabolised primarily by the hepatic
      cytochrome P450 enzyme system, and common genetic polymorphisms of the CYP 2C19
      iso-enzyme affect their clearance and bio-availability. This has been
      demonstrated to lead to inconsistency in terms of acid suppression across the CYP
      2C19 genotypes for all proton pump inhibitors except for rabeprazole. Omeprazole
      and, more markedly, esomeprazole, differ from the other proton pump inhibitors in
      that their bio-availability increases over the first week of treatment. This is
      due to a progressive reduction in their hepatic clearance with repeat dosing.
      This reduced hepatic clearance appears to be due to the S-enantiomer of
      omeprazole-esomeprazole impairing the activity of hepatic CYP 2C19. The clinical
      significance of these differences in metabolism of the various proton pump
      inhibitors, and the possible benefits of the non-enzymatic metabolism of
      rabeprazole, require further investigation.

PMID- 12236478
TI  - Dreams: the royal road to the intestines?

PMID- 12236479
TI  - Mid- and long-term quality of life assessments after laparoscopic fundoplication
      and refundoplication: a single unit review of more than 500 antireflux
      procedures.
AB  - BACKGROUND: For the evaluation of surgical interventions, quality of life data
      are being increasingly used as an efficacy endpoint. AIMS: To evaluate impact of
      laparoscopic fundoplication and laparoscopic refundoplication on quality of life
      as well as on patient satisfaction with the procedure for at least 5 years after
      surgical intervention. PATIENTS: After more than 500 laparoscopic antireflux
      procedures, quality of life data have been prospectively reviewed and data
      compared with healthy individuals, untreated gastro-oesophageal reflux disease
      patients (n = 150) and successfully treated patients (n = B4) under adequate
      omeprazole therapy. METHODS: Gastrointestinal Quality of Life Index has been used
      in all patients and evaluated the day before surgery and 5 times after surgery.
      Moreover, the SF-36 questionnaire has been used up to 2 years after surgical
      intervention, but only in patients who underwent laparoscopic redo-surgery (n =
      49). RESULTS: In both surgical groups, mean preoperative Gastrointestinal Quality
      of Life Index showed a significant (p < 0.01) impairment (before laparoscopic
      antireflux surgery: 90.4 +/- 10.3 points; before redo-surgery: 84.3 +/- 8.1
      points) when compared with healthy individuals (mean: 122.6 +/- 8.5 points) and
      successfully treated patients with acid-suppressive therapy (mean: 121.4 +/- 9.2
      points). After surgery, the mean Gastrointestinal Quality of Life Index increased
      significantly and remained stable for at least 5 years after laparoscopic
      antireflux surgery (120.8 +/- 8.6 points) or for at least 2 years after redo
      proce-dure (120.9 +/- 7.2 points). Before laparoscopic refundoplication, 6 out of
      8 SF-36 scores were significantly p < 0.05) decreased. Redo-surgery influenced
      these 6 scores significantly (p < 0.05-0.01), resulting in values comparable to
      those of general population. Patients' satisfaction with surgery was excellent or
      good in 95%. CONCLUSION: Both, laparoscopic fundoplication as well as
      laparoscopic refundoplication are able to improve patients' quality of life
      significantly for at least 5 years. Therefore, quality of life data provide
      useful information to discuss different treatment options with patients.

PMID- 12236480
TI  - Gastric emptying and duodeno-gastro-oesophageal reflux in gastro-oesophageal
      reflux disease.
AB  - BACKGROUND: Previous studies present conflicting results regarding relationship
      between gastric emptying and gastro-oesophageal reflux disease. Reflux of
      duodenal content to oesophagus is generally considered to be associated with more
      severe disease. AIM: To assess presence of a gastric emptying disorder in persons
      with reflux of duodenal contents to oesophagus and to identify any correlation
      with gastric emptying and oesophageal motility. METHODOLOGY: A total of 15
      subjects with (B+) and 15 subjects without (B-) bile reflux to oesophagus
      determined by 24-hour bilirubin monitoring were studied with scintigraphic solid
      gastric emptying and 24-hour oesophageal manometry. RESULTS: There was no
      difference in lag phase [median 23.7 (range 10.8-44.0) vs 24.6 (8.1-40.1) min],
      half emptying time [74.6 (48.0-93.6) vs 82.8 (54.4-153.9) min] or emptying rate
      [0.89 (0.59-1.34) vs 0.83 (0.36-1. 15)%/min] for B- and B+ subjects,
      respectively. In addition, there was no difference in emptying rate of gastric
      fundus between B- and B+ subjects. Subjects with bile reflux had less effective
      oesophageal contractions of oesophageal body [9.4(3.3-37)%] compared to subjects
      without bile reflux [32(19-47)%, p = 0.002]. However, there was no correlation
      between oesophageal motility and gastric emptying. CONCLUSION: Results suggest
      that a gastric emptying disorder is a less likely contributing cause of bile
      reflux to the oesophagus, but bile reflux is associated with less effective
      oesophageal motility.

PMID- 12236481
TI  - Gastric emptying in myotonic dystrophic patients.
AB  - BACKGROUND: Myotonic dystrophy is often associated with digestive symptoms that
      can precede the clinical appearance of skeletal muscle involvement. Although
      motility disorders may be observed in these patients at any level of the
      gastrointestinal tract, upper gastrointestinal symptoms have up to now usually
      been considered to be due to oesophageal rather than gastric dysmotility. AIMS:
      To evaluate: a) gastric emptying in myotonic dystrophic patients without
      dyspeptic symptoms, and b) relationship between gastric emptying and severity and
      duration of the disease. PATIENTS AND METHODS: Gastric emptying was evaluated in
      11 non-dyspeptic dystrophic patients and in 22 healthy volunteers by means of
      computerised ultrasound scan, assessing the variation in the antral area over
      time after ingestion of a meal. RESULTS: The final emptying time was higher in
      patients than in healthy volunteers (373' +/- 35' vs 270' +/- 47'; p < 0.001).
      Basal and maximal post-prandial antral areas were similar in the two groups.
      There was a significant correlation between gastric emptying and the duration of
      the disease (rs = 0.62; p = 0.04). No relationship was found between gastric
      emptying and severity of the disease. CONCLUSIONS: Gastric emptying may be
      abnormally delayed in myotonic dystrophy patients, even in absence of dyspeptic
      symptoms. This delay is correlated with duration but not with severity of the
      disease. However there is no difference in either basal or maximal postprandial
      antral areas between myotonic dystrophy patients and healthy volunteers.

PMID- 12236482
TI  - Lower concentrations of clarithromycin suppress urease activity, motility, and
      binding to gastric epithelial cells in Helicobacter pylori isolates.
AB  - BACKGROUND: Our previous study showed that histological scores of gastric mucosal
      inflammation and Helicobacter pylori density decreased even in patients who
      failed to eradicate Helicobacter pylori after antimicrobial therapy including
      clarithromycin. This may reflect indirect suppressive effects of lower
      concentrations of clarithromycin on Helicobacter pylori, as suggested in other
      Gram-negative rod infections. AIMS: To investigate whether clarithromycin
      suppresses virulence factors of Helicobacter pylori at sub-minimal inhibitory
      concentration. METHODS: Six clarithromycin-susceptible Helicobacter pylori
      isolates and 7 clarithromycin-resistant isolates were obtained from patients with
      peptic ulcer disease. These isolates were analysed for urease activity, motility,
      and ability to bind to gastric epithelial cells after they were incubated with or
      without clarithromycin at sub-minimal inhibitory concentrations. RESULTS:
      Incubation of Helicobacter pylori isolates with clarithromycin at sub-minimal
      inhibitory concentrations reduced urease activity motility, and binding to
      gastric epithelial cells in a dose-dependent manner. These findings were observed
      both in clarithromycin-susceptible and resistant strains. CONCLUSIONS:
      Suppressive effects of clerithromycin on virulence factors of Helicobacter pylori
      at sub-minimal inhibitory concentrations may be associated with observed
      attenuation of gastric inflammation and Helicobacter pylori density in patients
      who failed in bacterial eradication after triple therapy including
      clarithromycin.

PMID- 12236483
TI  - Up-regulation of heparin binding epidermal growth factor-like growth factor and
      amphiregulin expression in Helicobacter pylori-infected human gastric mucosa.
AB  - BACKGROUND: Host response plays a major role in pathogenesis of Helicobacter
      pylori-induced gastroduodenal disease including adenocarcinoma of distal stomach.
      Epidermal growth factor-related growth factors are important modulators of
      gastric homeostasis in normal and damaged gastrointestinal mucosa. AIM: To
      evaluate expression of heparin binding epidermal growth factor and amphiregulin
      in antral mucosa of Helicobacter pylori-infected and non-infected dyspeptic
      patients and to correlate levels of heparin binding-epidermal growth factor and
      amphiregulin mRNA with mitogenic activity of gastric epithelial cells. METHODS: A
      total of 10 Helicobacter pylori-infected and 15 Helicobacter pylori non-infected
      (10 with and 5 without gastritis) dyspeptic patients were studied. Diagnosis of
      Helicobacter pylori infection was based on rapid urease test and histology.
      Heparin binding-epidermal growth factor and amphiregulin mRNA expression in
      antral mucosa were assessed by reverse transcriptase-polymerase chain reaction.
      Protein expression and localization of both peptides were determined by
      immunohistochemistry. Mitogenic activity of antral gastric mucosa was assessed by
      determination of proliferating cell nuclear antigen labelling index by
      immunohistochemistry. RESULTS: Heparin binding-epidermal growth factor and
      amphiregulin mRNA expression increased in Helicobacter pylori-infected vs
      Helicobacter pylori non-infected patients. Heparin binding-epidermal growth
      factor and amphiregulin immunostaining was more intense and deeper in gastric
      gland compartment in infected mucosa than in non-infected mucosa. Increase in
      heparin binding-epidermal growth factor and amphiregulin mRNA expression
      significantly correlated with increase in proliferating cell nuclear antigen
      labelling index. CONCLUSIONS: Helicobacter pylori gastritis is associated with up
      regulation of heparin binding-epidermal growth factor and amphiregulin which
      correlates with increased mitogenic activity of gastric mucosa. Increased heparin
      binding-epidermal growth factor and amphiregulin expression is postulated to
      contribute to reparative response of gastric mucosa to Helicobacter pylori
      infection.

PMID- 12236484
TI  - What do patients with irritable bowel syndrome dream about? A comparison with
      inflammatory bowel disease.
AB  - BACKGROUND: It is a common experience for people to dream of events about which
      they are either anxious or concerned. We therefore hypothesised that the dreams
      of patients with irritable bowel syndrome may reflect their worries about their
      problem especially as hospital out-patients with this disorder tend to exhibit
      some anxiety. In addition, dreaming about, for instance bowels, in patients with
      irritable bowel syndrome in excess of that observed in other gastrointestinal
      disorders may be of importance. AIM: To establish whether patients with irritable
      bowel syndrome dream about bowel-related issues more than controls or patients
      with inflammatory bowel disease. PATIENTS AND METHODS: A total of 57 patients
      with irritable bowel syndrome and 57 patients with inflammatory bowel disease
      were compared with 60 healthy controls. All subjects completed a structured
      questionnaire concerning sleeping habits and dream characteristics as well as an
      assessment of anxiety and depression. RESULTS: There were no differences in the
      sleeping habits between any of the groups. However, significantly more patients
      with irritable bowel syndrome and inflammatory bowel disease dreamt about their
      bowels (22% inflammatory bowel disease patients, 18% irritable bowel syndrome
      patients vs 3% of controls, p < 0.05 inflammatory bowel disease and irritable
      bowel syndrome vs controls) and soiling themselves (16% of inflammatory bowel
      disease patients, 14% of irritable bowel syndrome patients vs 2% of controls; p <
      0.05 inflammatory bowel disease and irritable bowel syndrome vs controls) than
      controls. CONCLUSION: Chronic gastrointestinal disorders, of both a functional
      and organic nature, may influence the nature of dreams. In those patients who
      dream about their symptoms, it would be interesting to know whether this affects
      the course of their disease, either positively or negatively, in any way.

PMID- 12236485
TI  - Long-term treatment with mesalazine and rifaximin versus rifaximin alone for
      patients with recurrent attacks of acute diverticulitis of colon.
AB  - BACKGROUND/AIMS: To compare efficacy of combined therapy with rifaximin and
      mesalazine versus rifaximin alone in treatment of patients with recurrent
      diverticulitis in order to evaluate: 1) rapidity in improvement of symptoms, 2)
      regulation of bowel attacks, 3) prevention of recurrence of diverticulitis.
      METHODS: A total of 218 consecutive eligible patients (131 males, 87 females age
      64.3 years, range 51-79), affected by diverticulitis were monitored. Of these,
      109 patients were treated with rifaximin 400 mg bid plus mesalazine 800 mg tid
      for 7 days, followed by rifaximin 400 mg bid plus mesalazine 800 mg bid for 7
      days/month (group A); 109 patients were treated with rifaximin 400 mg bid for 7
      days, followed by rifaximin 400 mg bid for 7 days/month (group B). Colonoscopy
      was performed after 3, 6 and 12 months of therapy. RESULTS: At end of follow-up,
      193 patients were fully compliant to therapy Two patients died during study (1 in
      group A, 1 in group B), while four patients were lost to follow-up [1 in group A
      (0.91%) and 3 in group B (2.75%)]. The only side-effects recorded were transient
      urticaria (1 in group B, 0.91%) and epigastric pain (9 in group A, 8.25%).
      Severity of symptoms improved significantly in group A vs group B within 3 months
      (p < 0.005, p < 0.001 and p < 0.0001 and p < 0.0005 at 3, 6, 9 and 12 months,
      respectively). Bowel habits inproved significantly in group A vs group B within 3
      months (p < 0.005, p < 0.0005, p < 0.001 and p < 0.0001 at 3,6,9 and 12 months
      respectively). Symptomatic recurrence of diverticulitis occurred in 3 patients in
      group A, while 13 patients showed recurrence of diverticulitis in group B (p <
      0.005) during follow-up. CONCLUSIONS: This study clearly shows that rifaximin
      plus mesalazine are more effective than rifaximin alone in resolution of symptoms
      and prevention of recurrence of diverticulitis.

PMID- 12236486
TI  - Increased liver echogenicity at ultrasound examination reflects degree of
      steatosis but not of fibrosis in asymptomatic patients with mild/moderate
      abnormalities of liver transaminases.
AB  - AIMS: To investigate whether hyperechogenicity of liver can reliably be
      interpreted as liver steatosis and if any concomitant or isolated fibrosis can be
      disclosed. PATIENTS AND METHODS: A series of 165 patients with no signs or
      symptoms of liver disease referred because of slightly to moderately raised
      aminotransferases (alanine aminotransferase and/or aspartate aminotransferase 0.7
      5.0 microkat/l) for more than 6 months were prospectively investigated with a
      comprehensive laboratory profile, ultrasound examination of liver and
      percutaneous liver biopsy Fibrosis was assessed quantitatively and according to
      Metavir. Steatosis was graded as none, mild, moderate or severe. RESULTS: Of 98
      (59.4%) patients with raised echogenicity, 85 (86.7%) had liver steatosis of at
      least moderate degree, 9 patients with same degree of steatosis had normal
      echogenicity and 13 patients with no or only mild steatosis had a hyperechogenic
      liver (sensitivity 0.90, specificity 0.82, positive predictive value 0.87,
      negative predictive value 0.87). About the same relations were found regardless
      of body mass index and degree of fibrosis. With increased echogenicity together
      with high attenuation (n = 591 and reduced portal vessel wall distinction (n =
      79), positive predictive value increased to 0.93 and 0.94, respectively.
      Quantitatively assessed fibrosis (mean +/- SD) was 3.2 +/- 4.6% of biopsy area
      with normal and 2.3 +/- 1.8% with raised echogenicity (ns). Echogenicity was
      normal in 5 out of 9 patients with septal fibrosis and in 4 out of 6 patients
      with cirrhosis. Any structural, non-homogenous findings at ultrasound were not
      associated with architectural fibrotic changes and none had nodular contours of
      liver surface. CONCLUSIONS: Assessment of liver echogenicity is of value for
      detection or exclusion of moderate to pronounced fatty infiltration (correct
      classification 86.6%) but cannot be relied upon in diagnosing fibrosis, not even
      cirrhosis in asymptomatic patients with mild to moderately elevated liver
      transaminases.

PMID- 12236487
TI  - Improved liver tests and greater biliary enrichment with high dose
      ursodeoxycholic acid in early stage primary biliary cirrhosis.
AB  - BACKGROUND: Ursodeoxycholic acid is currently used for the treatment of primary
      biliary cirrhosis at 13-15 mg/kg/day, but liver tests of some patients do not
      return to normal at this dose. Studies reported here were designed to test
      whether a higher dose of ursodeoxycholic acid than is currently used would induce
      still greater biliary enrichment of ursodeoxycholic acid and whether such
      enrichment would lead to still further improvement in liver tests in patients
      with early primary biliary cirrhosis. METHODS: A total of 20 patients with
      histologically proven primary biliary cirrhosis were enrolled. Patients had early
      stage primary biliary cirrhosis as serum bilirubin levels were normal and the
      Mayo risk score 4.2 +/- 0.5. Group 1 received 600, 1200 and 1800 mg/day of
      ursodeoxycholic acid; group 2 received 900, 1500 and 2100 mg/day. The order of
      periods was randomized. Each treatment period lasted 3 months followed by a
      further 3 months during which a standard dose of ursodeoxycholic acid was given.
      At the end of each treatment period, liver tests were evaluated, and biliary bile
      acid pattern of duodenal bile was determined using high pressure liquid
      chromatography. RESULTS: Biliary bile acid became enriched in ursodeoxycholic
      acid in direct relationship to dosage [r = 0.84, p < 0.001). At doses of 1800
      mg/day (25-35 mg/kg/day), biliary ursodeoxycholic acid averaged 69 +/- 6.6%. A
      progressive decrease of alanine aminotransferase [p < 0.0001), aspartate
      aminotransferase [p < 0.001) and alkaline phosphatase [p < 0.02) was observed
      with increasing concentrations of ursodeoxycholic acid in bile. Biochemical liver
      tests showed a stronger correlation with biliary concentrations of
      ursodeoxycholic acid than with the administered dose. CONCLUSIONS: In early
      primary biliary cirrhosis, higher dose ursodeoxycholic acid appears to be more
      effective than doses currently recommended.

PMID- 12236488
TI  - Tuberculous involvement of the oesophagus with oesophagobroncheal fistula.
AB  - Tuberculous involvement of the oesophagus is a rare disease. Even if it is
      suspected, diagnosis is often difficult though dysphagia and chest pain are the
      most common symptoms without any other specific signs of tuberculosis. The
      diagnosis is based on oesophagography, oesophagoscopy, bronchoscopy, and computed
      tomographic scan. Suspected tuberculosis can be confirmed with histology, smear,
      and culture. The two most common differential diagnoses are Crohn's disease and
      carcinoma. The case is reported of a female patient with tuberculous involvement
      of the oesophagus, who developed an oesophagobroncheal fistula during steroid
      treatment started for suspicion of Crohn's disease. The patient was
      immunocompromised due to treatment with azathioprine that she was receiving for
      multiple sclerosis. The fistula was successfully treated by antituberculous
      chemotherapy alone.

PMID- 12236489
TI  - Long-term follow-up of achalasia patients treated with botulinum toxin.

PMID- 12236490
TI  - Clinical trial with thickened feeding for treatment of regurgitation in infants.

PMID- 12236491
TI  - How do we correctly investigate intestinal permeability?

PMID- 12236492
TI  - In-line pressurized-fluid extraction-solid-phase extraction for determining
      phenolic compounds in grapes.
AB  - A new method of pressurized-fluid extraction coupled in-line with solid-phase
      extraction has been used for the extraction of phenolic compounds from grapes.
      The full extraction method is performed under an inert atmosphere. Five different
      solvents have been assayed using different extraction pressures and temperatures.
      Using two extraction stages with two different solvents, water and methanol,
      quantitative recovery for most of the assayed compounds has been found in the
      second extract. Only the most polar phenolic compound, gallic acid, was found
      distributed in both extracts. The application to real samples allows for a clean
      up of the extracts. Cinnamic esters like caftaric acid, cis and trans-coutaric
      acids were found only in the methanolic extract. The reproducibility for the new
      method was measured using both an inert solid spiked with standards and grapes.
      Using between 202 and 424 microg of spiked standards, the resulting relative
      standard deviations were less than 5%, with the exception of gallic acid
      (RSD=13%). For grapes, the resulting RSD were 11% for trans-coutaric acid, 10%
      for caftaric acid and 6% for cis-coutaric acid.

PMID- 12236493
TI  - Quantification of sugars and organic acids in hygroscopic pharmaceutical herbal
      dry extracts.
AB  - Three chromatographic methods have been employed for the determination of
      hydrophilic compounds, namely carbohydrates and organic acids in herbal dry
      extracts of Eschscholtzia californica Cham. The hydrophilic compounds were
      separated from the other components of the dry extracts by solid-phase extraction
      methods, which were optimised with respect to recovery rates. Carbohydrates were
      quantified using high-performance anion-exchange chromatography with pulsed
      amperometric detection. Organic acids were analysed by ion-exclusion
      chromatography with evaporative light scattering detection and gas chromatography
      mass spectrometry. Using the latter method, large amounts of glyceric acid were
      separated from the extracts of Eschscholtzia californica Cham. This substance
      together with sugars may be responsible for the increased hygroscopicity and the
      poor processing behaviour of the extracts.

PMID- 12236494
TI  - On-line purification of His-tag enhanced green fluorescent protein taken directly
      from a bioreactor by continuous ultrasonic homogenization coupled with
      immobilized metal affinity expanded bed adsorption.
AB  - In this report, we describe a new process for the on-line purification of His-tag
      EGFP (enhanced green fluorescent protein) taken directly from a bioreactor by
      continuous ultrasonic homogenization coupled with immobilized metal affinity
      expanded bed adsorption (IMAEBA). The use of proteins including a histidine-tag
      facilitates their subsequent purification after expression in many
      microorganisms. This meets the needs of scientific researchers as well as
      industrialists interested in purifying recombinant proteins. After evaluating the
      different flow-rates and ultrasonic probe sizes, the on-line purification was
      tested. After ultrasonic treatment, 70% of the cells were broken and 90% of free
      EGFP was recovered after IMAEBA. In our conditions, more than 450 mg of EGFP were
      obtained in 15 h. On-line bioreactor-ultrasonic probe-immobilized metal affinity
      expanded bed adsorption is a rapid automated technique for obtaining large
      quantities of pure EGFP.

PMID- 12236495
TI  - Hydrophobic interaction ligand selection and scale-up of an expanded bed
      separation of an intracellular enzyme from Saccharomyces cerevisiae.
AB  - A prototype Streamline-Phenyl matrix was evaluated in a hydrophobic interaction
      mode for the direct recovery of alcohol dehydrogenase (ADH) from yeast cell
      homogenate. At 5% breakthrough of ADH, a yield of 100% was obtained for a dynamic
      expanded bed capacity of 240 U(ADH)/ml matrix with a purification factor of 9.2.
      This compared with a dynamic capacity of 3013 U(ADH)/ml matrix for the packed bed
      equivalent and a purification factor of 18. In both systems the purification
      factor was found to increase simultaneously with a decrease in yield as the load
      of homogenate or breakthrough of ADH was increased. The expanded bed mode of
      operation conferred considerable robustness with respect to process fouling. No
      loss in yield was seen over five cycles of repeat loading with an unclarified
      homogenate. By contrast the packed bed media showed a decrease in yield from 86
      to 56% over the same period. Successful scale up of the expanded bed protocol for
      a 20% breakthrough was demonstrated over a fourfold increase in column diameter.
      The application of hydrophobic interaction chromatography mediated expanded bed
      adsorption and its scale-up is discussed in the context of large-scale
      operations.

PMID- 12236496
TI  - Simultaneous quantification of A-trichothecene mycotoxins in grains using liquid
      chromatography-atmospheric pressure chemical ionisation mass spectrometry.
AB  - An approach for simultaneous determination of the main type A-trichothecenes by
      liquid chromatography and atmospheric pressure chemical ionization mass
      spectrometry is described. Parameters for coupling of LC-MS such as cone voltage,
      nebulizing temperature and the LC flow-rate, were optimized to provide detection
      of mycotoxins with maximum sensitivity. Furthermore, the effects of cone voltage
      and temperature on the fragmentation pattern of the tested toxins were studied.
      Main type A-trichothecenes such as T-2 Toxin, HT-2 Toxin, acetyl T-2 Toxin,
      diacetoxyscirpenol, monoacetoxyscirpenol (15-acetoxyscirpenol) and neosolaniol
      were separated on a reversed-phase narrow bore C18 column, using a linear
      gradient and a flow-rate of 0.3 ml/min. Mass spectra were obtained in positive
      ion mode for confirmation and quantitation. The method involves extraction and
      purification of toxins by using multifunctional Mycosep columns. Deuterated T-2
      Toxin was used as an internal standard. A linear working range between 80 and 500
      microg/kg in matrix with an acceptable correlation coefficient was observed. The
      developed method was validated by using a blank oats sample. The detection limit
      in the matrix was found to be between 50 and 85 microg/kg in selected ion mode
      for all tested A-trichothecenes. Recovery data were found to be between 77 and
      101%. Within run and day-to-day precision were determined as having comparable
      levels to those found using GC methods. Furthermore, the matrix effect was
      investigated by comparing the internal standard versus the external standard
      method in quantification studies. In addition, the developed method was applied
      for the analysis of naturally contaminated oats, maize, barley and wheat samples.

PMID- 12236497
TI  - Determination of nonylphenol polyethoxylates in household detergents by high
      performance liquid chromatography.
AB  - Preliminary survey results of the content of nonylphenol polyethoxylates (NPEOs)
      in various household detergents sold in Taiwan are presented. This survey was
      conducted to elucidate the concentration of NPEOs in household detergents and
      support pollution prevention and control programs. The concentrations of NPEOs in
      detergents and cleaners were determined by HPLC with a C8 reversed-phase column
      and equipped with fluorescence detection. The accuracy and precision of the
      method was validated and was successfully applied to determine concentrations of
      NPEOs in household detergents. The results show that NPEOs were detected in 41%
      of 90 household detergents at concentrations from 0.2 to 21%. The highest
      concentration of NPEOs (21%) was detected in a laundry liquid especially designed
      for washing socks. Reversed-phase liquid chromatography connected with
      electrospray mass spectrometry confirmed the results.

PMID- 12236499
TI  - Retention time reproducibility in comprehensive two-dimensional gas
      chromatography using cryogenic modulation an intralaboratory study.
AB  - A survey was conducted to determine the reproducibility of retention times in
      both the first (D1) and second dimension (D2) axes of the two-dimensional
      separation space, in the comprehensive two-dimensional gas chromatographic
      analysis of an essential oil sample using cryogenic modulation. The retention
      times in the two dimensions for a number of individual components comprising
      hydrocarbon, alcohol, ester and ketone chemical classes in a Melaleuca
      alternifolia essential oil were recorded from replicate analyses using four
      separate column sets and two identical gas chromatographs. Run-to-run, day-to
      day, instrument-to-instrument, and column set-to-column set reproducibility were
      demonstrated from the experimental design. A total of 60 GC x GC analyses were
      conducted. The longitudinally modulated cryogenic system produced reproducible
      modulation start times and consistent modulation phase profiles for individual
      components in all experiments, and retention time variations in both dimensions
      were negligible. The average run-to-run reproducibility of 43 components for six
      replicate injections was found to be 0.12% RSD in the first dimension, and 0.74%
      RSD in the second dimension. Day-to-day reproducibility showed statistically
      "significant" difference (F-test), but this was partly ascribable to the
      excellent within-day reproducibility that led to apparent day-to-day differences.
      Confidence in absolute retention times (hence component positions) in the two
      dimensional separation space is critical to component identification.

PMID- 12236498
TI  - Mass spectrometric methods prove the use of beeswax and ruminant fat in late
      Roman cooking pots.
AB  - Lipid extracts of sherds of archaeological late Roman cooking pots were analysed
      using high temperature-gas chromatography coupled to a mass spectrometer and
      liquid chromatography with atmospheric pressure chemical ionization mass
      spectrometer detection (LC-APCI-MS). With these advanced techniques the use of
      beeswax was shown through identification of the constituting alkanes, mono and
      diesters. The detection of high amounts of saturated triacylglycerols (TAGs)
      further indicated that animal fat was processed in these pots. Part of the animal
      fat was characterised as originating from ruminants due to the presence of trans
      fatty acids. The distribution of saturated TAGs and the higher concentration of
      stearic acid compared to palmitic acid in the transesterified lipid extract
      indicated that this was sheep fat. The results illustrate how complex mixtures
      can be unravelled and original contents of ancient ceramic vessels can be
      determined using specialised analytical equipment.

PMID- 12236500
TI  - Mixed-mode reversed-phase and ion-exchange separations of cationic analytes on
      polybutadiene-coated zirconia.
AB  - The retention and selectivity of the chromatographic separation of basic
      (cationic) analytes on a polybutadiene-coated zirconia (PBD-ZrO2) stationary
      phase have been studied in greater detail than in previous studies. These
      separations are strongly influenced by the chemistry of the accessible surface of
      zirconia. In the presence of buffers which contain hard Lewis bases (e.g.,
      phosphate, fluoride, carboxylic acids) zirconia's surface becomes negatively
      charged due to adsorption of the buffer anion at the hard Lewis acid sites.
      Consequently, under most conditions (e.g., neutral pH), cationic analytes undergo
      both hydrophobic and cation-exchange interactions. This mixed-mode retention
      process generally leads to greater retention factors for cations relative to
      those on silica-based reversed phases despite the lower surface areas of the
      zirconia phase, but, more importantly, adsorption of hard Lewis bases can be used
      to control the chromatographic selectivity for cationic analytes on these
      zirconia-based stationary phases. In contrast to our prior work, here we show
      that when mixed-mode retention takes place, both retention and selectivity are
      easily adjusted by changing the type of hard Lewis base buffer anion, the type of
      buffer counter-ion (e.g., sodium, potassium, ammonium), the pH, and the ionic
      strength of the eluent as well as the type and amount of organic modifier.

PMID- 12236501
TI  - Selective enrichment of sulfides, thiols and methylthiophosphates from water
      samples on metal-loaded cation-exchange materials for gas chromatographic
      analysis.
AB  - The suitability of using metal-loaded sorbents for solid-phase extraction to
      enrich organic sulfur compounds from water samples was studied. To test the
      retention behavior of a number of sulfides, thiols and methylthiophosphates, a
      cation-exchanger was loaded with various metal ions. The elution behavior of
      sulfur compounds was investigated with different solvents. A combination of Pb2+
      modified cation-exchanger as sorbent and CS2 (1%, v/v) in toluene proved to be
      the most suitable approach for the given problem. Using GC with a pulsed flame
      photometric detector yielded detection limits of between 0.6 and 2.9 microg/l.
      The results showed good reproducibility with relative standard deviations of 2
      11%.

PMID- 12236502
TI  - Multiresidue method for the simultaneous determination of four groups of
      pesticides in ground and drinking waters, using solid-phase microextraction-gas
      chromatography with electron-capture and thermionic specific detection.
AB  - A common sample preparation procedure capable of efficiently concentrating
      various groups of pesticides, taking advantage of universal detectors like the
      mass spectrometer or combined techniques of group selective detectors like gas
      chromatography-electron capture detection (ECD)/thermionic specific detection
      (TSD), is desirable in environmental analysis. Six solid-phase microextraction
      fibres available for analysis of semi-volatiles (7, 30 and 100 microm
      poly(dimethylsiloxane) (PDMS), 85 microm polyacrylate, 60 microm PDMS
      divinylbenzene (PDMS-DVB) and 65 microm Carbowax-DVB) were evaluated and the 60
      microm PDMS-DVB was selected for the simultaneous extraction of 34 compounds,
      included in the organochlorine (OCPs), organophosphorous (OPPs), pyrethroid and
      triazine pesticide groups. All parameters affecting the extraction efficiency
      from water samples, namely fibre coating, sample agitation, pH and ionic
      strength, extraction temperature and time, were optimised. The analytical
      procedure involves solid-phase microextraction extraction, gas chromatographic
      separation and subsequent ECD and TSD via a post-column splitter adjusted to a
      split ratio of 1:10, respectively. Detection limits in the range of 1-10 ng l(-1)
      for OCPs, 1-30 ng l(-1) for OPPs, 20-30 ng l(-1) for pyrethroids and 8-50 ng l(
      1) for triazines are easily attainable with the optimised procedure. The method
      validated for ground and drinking waters has low cost of implementation and
      operation although it requires careful maintenance.

PMID- 12236503
TI  - Determination of organochlorine pesticides in seawater using liquid-phase hollow
      fibre membrane microextraction and gas chromatography-mass spectrometry.
AB  - The use of hollow fibre membrane microextraction in analytical chemistry has been
      increasing as the technique is a simple and efficient method for the extraction
      of trace organic compounds from environmental matrices. A simple liquid-phase
      microextraction technique using a hollow fibre membrane in conjunction with gas
      chromatography-mass spectrometry has been developed for the extraction and
      analysis of organochlorine pesticides (OCPs), i.e. alpha-hexachlorocyclohexane
      (BHC), lindane, beta-BHC, heptachlor, aldrin, dieldrin, endrin, endosulfan, p,p'
      DDD, p,p'-DDT, endrin aldehyde and methoxychlor, from seawater. The technique
      requires minimal sample preparation time and solvent consumption, and represents
      a significant advantage over conventional analytical methods. Optimum extraction
      conditions have been evaluated with respect to sample pH, salt content and
      stirring rate, as well as solvent type and extraction time. A high level of
      detection linearity (coefficient of >0.9995, less than 14% RSD) was obtained for
      OCPs over a range of analyte concentrations between 5 and 100 microg l(-1), with
      detection limits in the parts per trillion (ppt) to sub-parts per billion range.
      Comparison between liquid-phase microextraction with hollow fibre membrane and US
      Environmental Protection Agency Method 508 showed that the novel method has
      comparable detection limits of between 0.013 and 0.059 microg l(-1) in seawater.

PMID- 12236504
TI  - Application of matrix solid-phase dispersion to the determination of a new
      generation of fungicides in fruits and vegetables.
AB  - A method based on matrix solid-phase dispersion (MSPD) and gas chromatography to
      determine eight fungicides in fruits and vegetables is described. Fungicide
      residues were identified and quantified using nitrogen-phosphorus detection and
      electron-capture detection connected in parallel and confirmed by mass
      spectrometric detection. The method required 0.5 g of sample, C18 bonded silica
      as dispersant sorbent, silica as clean-up sorbent and ethyl acetate as eluting
      solvent. Recoveries from spiked orange, apple, tomato, artichoke, carrot and
      courgette samples ranged from 62 to 102% and relative standard deviations were
      less than 15% in the concentration range 0.05-10 mg kg(-1). Detection and
      quantitation limits ranged 3-30 microg kg(-1) and 10-100 microg kg(-1),
      respectively, with linear calibration curves up to 10 mg kg(-1). The analytical
      characteristics of MSPD compared very favourably with the results of a classical
      multiresidue method, which uses ethyl acetate and anhydrous sodium sulphate for
      the extraction.

PMID- 12236505
TI  - Structural requirements for conserved Arg52 residue for interaction of the human
      immunodeficiency virus type 1 trans-activation responsive element with trans
      activator of transcription protein (49-57). Capillary electrophoresis mobility
      shift assay.
AB  - A sensitive capillary electrophoresis mobility shift assay (CEMSA) for
      qualitative study of the interaction between the trans-activation response
      element (TAR) and the trans-activator of transcription protein (Tat) has been
      presented. The human immunodeficiency virus type 1 (HIV-1) Tat promotes
      elongation of viral mRNAs binding to the TAR. It has been suggested that a
      single, conserved arginine residue (presumably Arg52) within the arginine-rich
      region (ARR) of Tat plays the major role for the Tat-TAR recognition. To study
      structural requirements of the Arg52 position, Tat(49-57)-NH2 analogues
      substituted with nonencoded amino acids at the Arg52 position have been
      synthesized and their interaction with TAR has been studied by CEMSA. Using a
      linear polyacrylamide-coated capillary and a sieving polymer containing
      separation buffer, well separated and shaped peaks of free and bound TAR RNA were
      obtained. In the presence of Tat1 peptide bearing the native sequence of Tat(49
      57) a significant shift of migration time of TAR from 18.66 min (RSD=1.4%) to
      20.12 min (RSD=2.4%) was observed. We have found that almost every substitution
      within the guanidino group of the Arg52 [L-Arg52-->Cit, -->Orn, -->Arg(NO2), -
      >Arg(Me2)] strongly disrupted or abolished the TAR-Tat peptide interaction.
      Enantiomeric substitution, L-Arg52-->D-Arg was the only one which notably
      promoted TAR-Tat peptide interaction. The results demonstrate that the specific
      net of hydrogen bonds created by the guanidinio group of conserved Arg52 plays a
      crucial role for TAR-Tat HIV-1 recognition. The newly developed procedure
      describes for the first time use of CE to monitor RNA-peptide complex formation.
      The methodology presented should be generally applicable to study RNA-peptide
      (protein) interaction.

PMID- 12236506
TI  - Improved capillary isoelectric focusing method for recombinant erythropoietin
      analysis.
AB  - Human erythropoietin (EPO) is an endogenously produced glycoprotein, which plays
      a key role in the erythropoiesis process. Production of erythropoietin by
      recombinant DNA techniques has made possible its therapeutical use besides its
      misuse in sport competitions. The link between glycosylated form and protein
      activity makes necessary a method to analyze the glycoforms' distribution in the
      recombinant products. In this work, a capillary isoelectric focusing (cIEF)
      method is presented that allows the analysis of erythropoietin glycoforms.
      Besides, the cIEF method can be easily implemented in different laboratories. In
      order to get a feasible and precise cIEF method the following factors have been
      studied and optimized: (i) neutral coated capillaries, 27 cm long are employed,
      (ii) ampholytes in the pH range 2 to 10 are used, (iii) bovine beta-lactoglobulin
      A is chosen as internal standard, (iv) anolyte consisting of 91 mM H3PO4 in cIEF
      gel is made by weight and catholyte is prepared by titrating 20 mM NaOH with
      H3PO4 to pH 11.85-11.90, (v) sample is completely depleted of excipients and
      sodium chloride 10 mM final concentration is added, and (v) t(n)/t(I.S.) and
      (A(n) - A(I.S.))/A(I.S.), n being the recombinant EPO glycoform considered and
      I.S. the internal standard, are chosen as indexes to express migration time and
      area. As a result, a precise method to analyze erythropoietin by capillary
      isoelectric focusing is achieved with intra-assay RSD < or = 0.5% for index time
      and < or = 1.5% for index area and inter-sample, inter-anolyte, and inter
      catholyte precision better than 3.4% for index time and RSD lower than 2.2% for
      index area.

PMID- 12236507
TI  - Optimizing separation conditions for riboflavin, flavin mononucleotide and flavin
      adenine dinucleotide in capillary zone electrophoresis with laser-induced
      fluorescence detection.
AB  - A method was developed for the quantitative determination of riboflavin, flavin
      mononucleotide (FMN) and flavin adenine dinucleotide (FAD), using free solution
      capillary zone electrophoresis in uncoated fused-silica capillaries with laser
      induced fluorescence (LIF) detection. Various factors influencing the separation
      and detection of flavin vitamers were investigated, including pH (5.5-10.5),
      concentration and nature of the run buffer (phosphate, borate and carbonate),
      applied voltage (15-30 kV), temperature (15-30 degrees C) and injection time.
      Optimal resolution and detection were obtained with a pH 9.8, 30 mM aqueous
      phosphate buffer at 15 degrees C and 30 kV of applied voltage. LIF detection was
      obtained with a He-Cd laser source using an excitation wavelength at 442 nm and
      lambda(em) > or = 515 nm. Riboflavin could be determined in the concentration
      ranges 0.5-350 microg/l with a rather low detection limit (LOD) down to 50 amol.
      The LODs of FAD and FMN were slightly higher, 300 and 350 amol, respectively.
      Combined with a simple clean-up procedure, the practical utility of this method
      is illustrated by the measurements of flavin derivates in foods and beverages,
      such as wines, milk, yoghurt and raw eggs.

PMID- 12236508
TI  - Optimization of the separation of Vinca alkaloids by nonaqueous capillary
      electrophoresis.
AB  - A rapid method for the determination of Vinca alkaloids by nonaqueous capillary
      electrophoresis with diode array detection has been developed. A group of 11
      alkaloids (catharanthine, vinorelbine, anhydrovinblastine, vinflunine, vindoline,
      4-O-deacetylvinorelbine, 4-O-deacetylvinflunine, vindesine, vinblastine, 4'-deoxy
      20',20'-difluorovinblastine, vincristine) could be readily separated within 10
      min. The compounds were separated using a capillary of 38 cm effective length, a
      running buffer composed of 50 mM ammonium acetate and 0.6 M acetic acid in a
      methanol-acetonitrile (75:25, v/v) mixture. A constant voltage of 25 kV with a
      ramp time of 1 min and a 344.7 x 10(3) Pa pressure, applied simultaneously to
      inlet and outlet buffer vials, were used during sample analysis. Five of these
      alkaloids were selected for optimization of the separation and for validation
      studies with respect to specificity, linearity, range, limits of quantification
      and detection and then accuracy. The feasibility of the assay was demonstrated by
      analyzing a commercial sample of vinorelbine (Navelbine, ampoule at 10 mg/ml of
      vinorelbine base). The results were compared with a high-performance liquid
      chromatography method.

PMID- 12236509
TI  - Supercritical fluid extraction for the detection of 2-dodecylcyclobutanone in low
      dose irradiated plant foods.
AB  - Supercritical carbon dioxide extraction [152 bar (15,200 kPa), 80 degrees C, 4 ml
      min(-1), 60 min], performed on lipids (2 g) previously extracted from irradiated
      plant foods, allowed a selective extraction of 2-dodecylcyclobutanone and its
      further detection by gas chromatography-mass spectrometry in 50 Gy irradiated
      cowpeas and 100 Gy irradiated rice. However, because of the higher quantities of
      lipid impurities in these test samples compared to those present in meat samples,
      a longer and slightly more polar capillary column than the one proposed in the
      official standard EN 1785 method should be used to obtain a satisfactory
      resolution.

PMID- 12236510
TI  - Application of pressurized liquid extraction technology to pharmaceutical solid
      dosage form analysis.
AB  - The technique of pressurized liquid extraction has been evaluated for the
      extraction of active ingredients from pharmaceutical dosage forms using
      montelukast sodium oral chewable tablets as a model. The extraction method was
      optimized for the number of extraction cycles, extraction time, extraction
      solvent composition and temperature. Samples were extracted using two cycles of
      water for 2 min with a cell temperature of 40 degrees C and a pressure of 1.0 x
      10(4) kPa, to disintegrate the tablet, followed by three cycles of methanol for 3
      min at 70 degrees C and 1.0 x 10(4) kPa, to solubilize montelukast sodium. The
      method demonstrated an extraction efficiency of 98.2% of label claim and an RSD
      of 1.3% (n=10), as compared to 97.6% and an RSD of 0.9% obtained using a
      validated mechanical extraction method.

PMID- 12236511
TI  - Application of a pulse-discharge helium detector to the determination of neon in
      air and water.
AB  - A pulse-discharge helium detector (Valco, PD-D2-I) is used to measure neon
      concentrations in air and water. The detection level is 0.5 x 10(-8) g/cm3 (0.2
      ppm). Discharge gas doped with neon results in a linear response to the neon mass
      up to 10(-6) g. For measuring the neon concentration in water, a simple
      enrichment system is used.

PMID- 12236512
TI  - Enantiomer separation of flavour and fragrance compounds by liquid chromatography
      using novel urea-covalent bonded methylated beta-cyclodextrins on silica.
AB  - A novel methylated beta-cyclodextrin chiral stationary phase (CSP-ME), which was
      chemically immobilised onto porous silica via multiple urea-linkages was
      synthesised. The CSP-ME chiral stationary phase depicted good enantiomer
      separation abilities for some well-known flavour as well as fragrance compounds
      using high-performance liquid chromatography under reverse phase conditions. The
      optimum resolution for alpha-ionone, 3-methyl-alpha-ionone, flavanone, 5
      methoxyflavanone, 6-methoxyflavanone, 7-methoxyflavanone, hesperetin, naringenin
      and taxifolin was achieved using a mobile phase composition consisting of 1 wt.%
      triethylammonium acetate buffer (pH 4.68)-methanol. The effects of pH of
      triethylammonium acetate buffer and the methanol-acetonitrile content of the
      mobile phase composition on their retention time and resolution were examined to
      optimise the separation conditions.

PMID- 12236513
TI  - Development of a two-dimensional liquid chromatography system with trapping and
      sample enrichment capabilities.
AB  - A two-dimensional HPLC system was developed where "heart-cutting" chromatography,
      in conjunction with cold temperature trapping, was used to isolate and
      concentrate specific sample analytes. Low molecular mass polystyrene oligomers
      were used as model compounds to illustrate the operation of the instrument and
      evaluate the performance of the trapping system. A critical factor in the
      operation of the trapping system was the relative degree of retention between the
      first column and the trapping column. The results of this study showed that up to
      32 consecutive heart-cut fractions from the first separation dimension could be
      stored in a trapping column with good analyte recovery and without significant
      loss in resolution upon elution on the second separation dimension.

PMID- 12236514
TI  - High-performance liquid chromatographic determination of oligomeric procyanidins
      from dimers up to the hexamer in hawthorn.
AB  - An HPLC method using UV diode array detection was developed for analysing
      procyanidins qualitatively and quantitatively up to the hexameric level in
      hawthorn samples. The analysed compounds included procyanidin dimers B-2, B-4 and
      B-5, procyanidin trimers C-1, epicatechin-(4beta-->8)-epicatechin-(4beta-->6)
      epicatechin and epicatechin-(4beta-->6)-epicatechin-(4beta-->8)-epicatechin, a
      tetramer D-1 and a pentamer E-1 both consisting of (-)-epicatechin units linked
      through C-4beta/C-8 bonds. The concentrations of two unknown tetramers and a
      hexamer F were also quantified. The oligomeric procyanidins (OPs) were
      specifically determined due to the development of a method for isolating them
      from hawthorn during sample preparation. The pattern of oligomeric procyanidins
      in the leaves, flowers and fruits was similar, but the concentrations varied
      depending on the part of the plant. The concentration in leaves was 1.6%, in
      flowers 1.2% and in fruits 0.2% of the dry mass. The method was validated with
      respect to repeatability, recovery, linearity, and sensitivity. The repeatability
      for the quantitative analytical method of all the OPs in leaves was 7.7%, in
      flowers 8.8%, and in fruits 12.3%. The recovery of the main OPs ranged from 91 to
      97%. The correlation coefficients of calibration curves were between 0.997 and
      1.000. The limits of quantitation for different procyanidin standards were 0.05
      0.12 mg/ml, when 10 microl of each standard solution was injected into the HPLC.

PMID- 12236515
TI  - Direct detection of yessotoxin and its analogues by liquid chromatography coupled
      with electrospray ion trap mass spectrometry.
AB  - A liquid chromatography mass spectrometry (LC-MS) method is proposed for the
      sensitive, specific and direct detection of yessotoxin and its analogues, marine
      biotoxins which are associated with diarrhetic shellfish poisoning (DSP) and
      which have been found in the North Adriatic sea since 1995. The LC-MS method
      provided a detection limit of 70 pg for yessotoxin in full scan mode and was
      applied to determine the toxic profiles of a number of extracts or partially
      purified fractions of toxic mussels collected along the Emilia Romagna coasts
      (Italy) in the period 1995-1999. Detection of a desulfo-yessotoxin derivative
      from Mytilus galloprovincialis collected in 1998 is also reported.

PMID- 12236516
TI  - Estimation of soil organic partition coefficients: from retention factors
      measured by soil column chromatography with water as eluent.
AB  - The retention factors (k) of 104 hydrophobic organic chemicals (HOCs) were
      measured in soil column chromatography (SCC) over columns filled with three
      naturally occurring reference soils and eluted with Milli-Q water. A novel method
      for the estimation of soil organic partition coefficient (Koc) was developed
      based on correlations with k in soil/water systems. Strong log Koc versus log k
      correlations (r>0.96) were found. The estimated Koc values were in accordance
      with the literature values with a maximum deviation of less than 0.4 log units.
      All estimated Koc values from three soils were consistent with each other. The
      SCC approach is promising for fast screening of a large number of chemicals in
      their environmental applications.

PMID- 12236517
TI  - Analysis of oligoguluronic acids with NMR, electrospray ionization-mass
      spectrometry and high-performance anion-exchange chromatography.
AB  - Oligoguluronates were prepared by enzymatic hydrolysis of homopolymeric blocks of
      guluronic acids. Two different oligosaccharides were prepared by separating final
      hydrolysates on Q-Sepharose FF ion chromatography. High-performance anion
      exchange chromatography analysis showed the high purity of these
      oligosaccharides. The molecular masses of these two oligosaccharides, determined
      by electrospray ionization-mass spectrometry, were 396 and 594, respectively. 1H,
      13C NMR, H-H COSY and HSQC analysis proved that they were the unsaturated dimer
      and trimer oligoguluronates. The 1H and 13C NMR chemical shifts of these two
      oligosaccharides are also reported.

PMID- 12236518
TI  - Ion chromatography characterization of polysaccharides in ancient wall paintings.
AB  - An analytical procedure for the characterisation of polysaccharides and the
      identification of plant gums in old polychrome samples is described. The
      procedure is based on hydrolysis with 2 M trifluoroacetic acid assisted by
      microwaves (20 min, 120 degrees C, 500 W), clean-up of the hydrolysate by an ion
      exchange resin, and analysis by high-performance anion-exchange chromatography
      with pulsed amperometric detection. Using this method the hydrolysis time was
      reduced to 20 min and the chromatographic separation of seven monosaccharides
      (fucose, rhamnose, arabinose, galactose, glucose, mannose, xylose) and two uronic
      acids (galacturonic and glucuronic) was achieved in 40 min. The whole analytical
      procedure allows sugar determination in plant gums at picomole levels, with an
      average recovery of 72% with an RSD of 8% as tested on arabic gum. The analytical
      procedure was tested with several raw gums, watercolour samples and reference
      painting specimens prepared according to old recipes at the Opificio delle Pietre
      Dure of Florence (Italian Ministry of Cultural Heritage, Italy). All the data
      collected expressed in relative sugar percentage contents were submitted to
      principal components analysis for gum identification: five groups were spatially
      separated and this enabled the identification of arabic, tragacanth, karaya,
      cherry+ghatty, and guar+locust bean gum. Wall painting samples from Macedonian
      tombs (Greece) of the 4th-3rd Centuries B.C., processed by the suggested method,
      showed the presence of a complex paint media mainly consisting of tragacanth and
      fruit tree gums. Moreover, starch had probably been added to plaster as
      highlighted by the presence of a huge amount of glucose.

PMID- 12236519
TI  - Simultaneous microanalysis of N-linked oligosaccharides in a glycoprotein using
      microbore graphitized carbon column liquid chromatography-mass spectrometry.
AB  - We previously reported that graphitized carbon column liquid chromatography-mass
      spectrometry (GCC-LC-MS) is very useful for the structural analysis of
      carbohydrates in a glycoprotein. In this study, GCC-LC-MS was adapted for the
      simultaneous microanalysis of oligosaccharides. A variety of oligosaccharide
      alditols prepared from fetuin, ribonuclease B, and recombinant human
      erythropoietin were used as model oligosaccharides. The use of microbore GCC-LC
      MS was found to be successful for rapid, sensitive, and simultaneous analysis of
      high-mannose-type, desialylated fucosyl complex-type, sialylated complex-type,
      and sialylated fucosyl complex-type oligosaccharide alditols. Furthermore, we
      demonstrate that this method is applicable to the analysis of carbohydrate
      heterogeneity in a glycoprotein that possesses diverse oligosaccharides.
      Microbore GCC-LC-MS was able to characterize high-mannose-type, hybrid-type, and
      complex-type oligosaccharides in tissue plasminogen activator produced from human
      melanoma cells in a single analysis.

PMID- 12236520
TI  - Mechanistic molecular model of liquid-solid chromatography retention-eluent
      composition relationships.
AB  - The development of a simple molecular model of liquid-solid chromatography
      leading to linear logarithmic relationships between retention factor and eluent
      composition is discussed. Further evolution of the model and its practical
      applications in method development are reviewed.

PMID- 12236521
TI  - Lipophilicity and pKa estimates from gradient high-performance liquid
      chromatography.
AB  - The linear-solvent strength (LSS) model of gradient elution has been applied to
      estimate parameters of lipophilicity and acidity of a series of drugs and model
      chemicals. Apparent pKa values and log kw values for individual analytes were
      determined in 2-3 gradient runs. The first experiment (or first two experiments)
      uses a wide-range organic modifier gradient with pH chosen for suppressed
      ionization of the analyte. The result of this experiment allows an estimate of
      contents of organic modifier of the mobile phase (%B) providing the required
      retention coefficient, k, for the non-ionized analyte. The following experiment
      is carried out with the latter %B and a pH-gradient of the aqueous component of
      the eluent that is sufficient to overlap the possible pKa-value of the analyte.
      The initial pH of the buffer used to make the mobile phase is selected to insure
      that the analyte is in non-ionized form. The resulting retention time allows an
      estimate of PKa in a solvent of the selected %B. At the same time, estimates of
      log kw can also be obtained. The log kw parameter obtained from gradient HPLC by
      the approach proposed correlated well with the corresponding value obtained by
      standard procedure of extrapolation of retention data determined in a series of
      isocratic measurements. Correlation between log kw and the reference parameter of
      lipophilicity, log P, was very good for a series of test analytes and
      satisfactory for a structurally diverse series of drugs. The approach supported
      with specific detection procedures can be recommended for fast screening of
      lipophilicity of individual components of complex mixtures like those produced by
      combinatorial chemistry. The values of pKa obtained in a study were found to
      correlate with the literature pKa data determined in water for a set of aniline
      derivatives studied. In case of a series of drugs the correlation was less than
      moderate if the general procedure of pKa determination was applied.

PMID- 12236522
TI  - Preparative liquid chromatography.
AB  - The status of the theory and the main methods of implementation of preparative
      liquid chromatography are reviewed. On the theory front, the focus has recently
      shifted. The theory of non-linear, non-ideal chromatography has given rise to
      numerous models whose advantages, disadvantages and ranges of application are now
      well understood. Interest now resides in investigating the equilibrium
      thermodynamics of complex new systems, in the study of the kinetics of mass
      transfers in conventional chromatographic systems, and in the application of the
      various models of chromatography to optimize the experimental conditions.
      Progress in computer technology allows the use of sophisticated models, provided
      their parameters can be measured. This allows the detailed investigation of
      separations for which the mass transfer kinetics is slow such as chiral
      separations, the purification of basic compounds, and the extraction of
      recombinant proteins. On the applied front, in addition to numerous incremental
      improvements in reliability and economic performance, a few essential new
      features should be noted, i.e. the availability of instruments for simulated
      moving bed separations at the scale needed for preparative chiral separations,
      the use of expanded beds for the extraction of recombinant proteins from
      fermentation broths, and the attention given to improvements in the performance
      of packed beds. A survey of the literature dealing with practical applications
      and recent meetings shows that preparative chromatography is becoming a well
      established separation and purification method in the pharmaceutical industry.

PMID- 12236523
TI  - Perspectives on analyses of nucleic acid constituents: the basis of genomics.
AB  - The recent mapping of the human genome was a tremendous achievement made possible
      to a large degree by the development of analytical methods for sequencing purine
      and pyrimidine bases in nucleic acids. In the last 3 decades, the number of
      analyses of nucleic acids and their constituents by HPLC and capillary
      electrophoresis (CE) has exploded. These techniques have been used not only for
      genomics, but also for the determination of free nucleotides, nucleosides and
      their bases in body fluids and tissues. Although a large number of HPLC and CE
      papers have been published on nucleic acid constituent applications, relatively
      little has been written on the mechanisms of the separations. However, to
      optimize analytical conditions knowledgeably and rapidly, it is important to know
      why and how these separations occur and the factors that affect them. The HPLC
      methods for the analysis of nucleic acid constituents and the information
      available on some of the mechanisms of separation of nucleotides, nucleosides and
      their bases, as well as the analysis of these compounds by CE and the factors
      that affect these separations are discussed.

PMID- 12236524
TI  - Computerized design of separation strategies by reversed-phase liquid
      chromatography: development of DryLab software.
AB  - The development of DryLab software is a special achievement in analytical HPLC
      which took place in the last 16 years. This paper tries to collect some of the
      historical mile stones and concepts. DryLab, being always subject to change
      according to the needs of the user, never stopped being developed. Under the
      influence of an ever changing science market, the DryLab development team had to
      consider not just scientific improvements, but also new technological
      achievements, such as the introduction of Windows 1.0 and 3.1, and later Windows
      NT and 2000. The recent availability of new 32-bit programming tools allowed
      calculations of chromatograms to be completed more quickly so as to show peak
      movements which result for example from slight changes in eluent pH. DryLab is a
      great success of interdisciplinary and intercontinental cooperation by many
      scientists.

PMID- 12236525
TI  - Temperature selectivity in reversed-phase high performance liquid chromatography.
AB  - Column temperature plays two important roles in reversed-phase high-performance
      liquid chromatography (RP-HPLC): control of retention (k) and control of
      selectivity (a). While changes in retention as a function of temperature are
      ubiquitous, selectivity changes for any given solute pair are more pronounced for
      ionized samples and samples with more polar substituents. With many samples,
      column temperature can be selected in a manner that optimizes resolution. The
      selectivity effects observed for temperature changes in RP-HPLC generally are
      complementary to those observed for mobile phase strength changes, so it is often
      possible to improve resolution by simultaneous optimization of temperature and
      mobile phase percent organic or gradient steepness. Computer simulation is a
      powerful tool for such optimization experiments. This paper reviews the influence
      of temperature on chromatographic selectivity for RP-HPLC.

PMID- 12236526
TI  - Comprehensive two-dimensional gas chromatography with time-of-flight mass
      spectrometric detection applied to the determination of pesticides in food
      extracts.
AB  - The separation provided by conventional gas chromatography (1D-GC) can be
      significantly enhanced by using comprehensive two-dimensional GC (GC X GC)
      instead. Combination with mass spectrometric detection is desirable for
      unambiguous confirmation of target compounds and the provisional identification
      of unknowns. A GC X GC system using a cryogenic modulator was coupled to a time
      of-flight mass spectrometric (TOF MS) detector. With the determination of
      pesticides in vegetable extracts as an example, it was demonstrated that GC X GC
      improves the separation dramatically. All 58 pesticides of interest could be
      identified using their full-scan mass spectra, which was not possible when using
      ID-GC-TOF MS. In addition, the high scan speed of the TOF MS allowed the
      deconvolution of compounds partly co-eluting in GC X GC.

PMID- 12236527
TI  - The measurement and meaning of void volumes in reversed-phase liquid
      chromatography.
AB  - The seemingly simple process of measuring the mobile phase volume, V0, in
      reversed-phase liquid chromatography has eluded unambiguous agreement for over 25
      years. Examples exist in the literature where the reported volume is physically
      impossible, either equal to or larger than the empty column volume, or being so
      small that it would represent a total porosity of half the theoretical limit for
      well-packed columns. Here we review the many proposals for methods of
      measurement, and compare and critique them. At this time, there is still no
      consensus for the best method of measurement, and workers are urged to critically
      examine values they measure, to insure they are at least physically possible.

PMID- 12236528
TI  - Bypass high-performance liquid chromatography for purification of trace analytes.
AB  - technique that we have termed "bypass HPLC" is introduced as a noncontaminating
      way to define the retention time of a trace analyte for purification purposes on
      an HPLC column when the amount of the analyte in real samples is too low for on
      line detection. The technique employs two HPLC columns ("calibration" and
      "purification") of the same type that are connected in parallel, with appropriate
      valving, along with use of two accessory compounds. By injecting ordinary (on
      line detectable) amounts of authentic analyte plus the two accessory compounds on
      the calibration column, and similarly the two accessory compounds onto the
      purification column, one can predict the retention of the analyte on the latter
      column without contaminating this column, as follows. The migration times of the
      first accessory compound provide a reference time on each column; the migration
      times of the second accessory compound are normalized on each column by
      subtracting the corresponding reference times; and then the retention time of
      analyte can be calculated on the second column since the ratio of its normalized
      retention times on the two columns equals the corresponding ratio for the second
      accessory compound.

PMID- 12236529
TI  - Gradient elution in normal-phase high-performance liquid chromatographic systems.
AB  - Gradient elution is widely used for separation of complex samples in reversed
      phase HPLC systems, but is less frequently applied in normal-phase HPLC, where it
      has a notoriously bad reputation for poor reproducibility and unpredictable
      retention. This behaviour is caused by preferential adsorption of polar solvents
      used in mixed mobile phases, which may cause significant deviations of the actual
      gradient profile from the pre-set program. Another important source of
      irreproducible retention behaviour is gradual deactivation of the adsorbent by
      adsorption of even traces of water during normal-phase gradient elution. To avoid
      this phenomenon, carefully dried solvents should be used. Finally, column
      temperature should be carefully controlled during normal-phase gradient elution
      if reproducible results are to be obtained. Working with dry solvents at a
      controlled constant temperature and using a sophisticated gradient-elution
      chromatograph, reproducibility of the retention data in normal-phase gradient
      elution better than 2% may be achieved even over several months of column use.
      The retention data in gradient elution can be calculated accurately if
      appropriate corrections are adopted for the gradient dwell volume and for the
      preferential adsorption of the polar solvents using experimental adsorption
      isotherms. The average error of prediction for the corrected calculated gradient
      retention data was lower than 2% for a silica gel column and lower than 3% for a
      bonded nitrile column, which may be suitable for the optimization of separation.
      Further, a simple approach is suggested for rapid estimation of changes in the
      retention induced by a change in the gradient profile in normal-phase HPLC. For
      such a rough estimation, it is not necessary to know the parameters of the
      dependence of the solute retention factors on the composition of the mobile
      phase.

PMID- 12236530
TI  - Atypical silica-based column packings for high-performance liquid chromatography.
AB  - Column packings widely used for high-performance liquid chromatography (HPLC)
      mostly are based on porous silica microspheres with certain pore sizes and pore
      size distributions. Such materials have the most desirable compromise of
      properties that provide for effective and reproducible separations over a wide
      range of operating conditions. To provide desired separation characteristics,
      several manufacturers specially synthesize the silica particles for these
      packings. While such column packing materials have general utility for a wide
      range of needs, special silica-based particles have been synthesized with
      different physical conformations for special separation goals. This presentation
      describes some atypical types of silica-based particles with unique separation
      properties that enlarge the capabilities of HPLC methods.

PMID- 12236531
TI  - Column selectivity from the perspective of the solvation parameter model.
AB  - The solvation parameter model is a useful tool for delineating the contribution
      of defined intermolecular interactions to retention of neutral molecules in
      separation systems based on a solute equilibrium between a gas, liquid or fluid
      mobile phase and a liquid or solid stationary phase. The free energy for this
      process is decomposed into contributions for cavity formation and the set up of
      intermolecular interactions identified as dispersion, electron lone pair, dipole
      type and hydrogen bonding. The relative contribution of these interactions is
      indicated by a series of system constants determined by the difference of the
      defined interaction in the two phases. The interpretation of these system
      constants as a function of experimental factors that affect retention in the
      chromatographic system provides the connection between relative retention
      (selectivity) and the control variables for the separation system. To aid in the
      understanding of these processes we perform an analysis of system constants for
      gas chromatography, liquid chromatography, supercritical fluid chromatography and
      micellar electrokinetic chromatography as a function of different experimental
      variables as a step towards gaining a theoretical understanding of selectivity
      optimization for method development.

PMID- 12236532
TI  - Comparative study of the linear solvation energy relationship, linear solvent
      strength theory, and typical-conditions model for retention prediction in
      reversed-phase liquid chromatography.
AB  - This paper describes two new retention models for predicting retention under
      different reversed-phase liquid chromatography (RPLC) conditions. The first one
      is a global linear solvation energy relationship (LSER) that expresses retention
      as a function of both solute LSER descriptors and mobile phase composition. The
      second is a so-called "typical-conditions model" that expresses retention under a
      given chromatographic condition as a linear function of retention under different
      so-called "typical" conditions. The global LSER was derived by combining the
      local LSER model and the linear solvent strength theory (LSST) of RPLC. Compared
      to local LSER and the LSST models, the global LSER model requires far fewer
      retention measurements for calibrating the model when different solutes and
      different mobile phase compositions are involved. Its fitting performance is
      equal to the local LSER model but worse than that of LSST. The poor fit of the
      global LSER results primarily from the local LSER model and not from the LSST
      model. The typical-conditions model (TCM) was developed based on a concept of
      multivariate space that is conceptually compatible with LSER. However, no LSER
      descriptors are used in the TCM approach. The number of input conditions needed
      in the typical-conditions model is determined by the chemical diversity of the
      solutes and the conditions involved. Principal component analysis (PCA) and
      iterative key set factor analysis (IKSFA) were used to find the number of typical
      conditions needed for a given data set. Compared to LSER, LSST, and global LSER,
      the typical-conditions model is more precise and requires fewer retention
      measurements for calibrating the model when different solutes and different
      stationary and/or mobile phases are involved.

PMID- 12236533
TI  - Comparison of methods for characterization of reversed-phase liquid
      chromatographic selectivity.
AB  - The goal of the present work is to obtain a better understanding of the chemical
      factors affecting liquid chromatographic retention. One of the most commonly used
      formats for liquid chromatographic separations is based on a nonpolar stationary
      phase, typically an octadecyl-derivatized silica material. A wide variety of
      these reversed-phase columns are commercially available that differ significantly
      in their chromatographic retention and selectivity. We seek to quantitatively
      characterize these differences. Retention data for a range of compounds with many
      diverse characteristics have been measured on several different octadecyl silica
      columns (J. Chromatogr. A, submitted for publication). Principal components
      analysis is used to characterize the different properties of these stationary
      phases and predict retention factors. The key set factor analysis method and the
      typical solute method are used in conjunction with the principal components
      analysis to identify small subsets of solutes that can be used to quantitatively
      describe the retention of a broad range of compounds. In addition, a quantitative
      comparison to alternative data analysis methods is made, including linear
      solvation energy relationships and an iterative subtraction method based on
      linear regression techniques. Although many earlier studies have reported the
      application of these methods, this study is the first to make a quantitative
      comparison of these methods using a highly precise and structurally variable set
      of test compounds.

PMID- 12236534
TI  - Practice and theory of enantioselective complexation gas chromatography.
AB  - The practice and theory of enantioselective complexation GC is comprehensively
      reviewed for the first time. A multitude of racemic oxygen-, nitrogen- and sulfur
      containing selectands can be separated without prior derivatization into
      enantiomers by complexation GC on optically active metal(II) bis[3
      (perfluoroacyl)-(1R)-camphorate] selectors. Peak inversion is obtained when the
      selectors with opposite configuration are employed. Applications pertain to
      chiral analysis in asymmetric synthesis, enzymatic reactions, pheromone and
      flavour chemistry. Although the use of enantioselective complexation GC has
      diminished recently with the advent of modified cyclodextrins in enantioselective
      GC, the inherent principles of enantiorecognition together with other
      enantioselective phenomena can be elucidated easily by complexation GC. Using the
      concept of the retention-increment R' which allows the distinction between non
      enantioselective and enantioselective contributions to retention, concise
      thermodynamic parameters of enantioselectivity - deltaD,L(deltaG) are accessible.
      The enantiomerization of configurationally labile enantiomers can be investigated
      and quantified by complexation GC. Four distinct enantioselective processes and
      four different coalescence phenomena have been discerned in complexation GC.

PMID- 12236535
TI  - Monolithic silica columns for high-efficiency chromatographic separations.
AB  - Studies on the structural and chromatographic properties of monolithic silica
      columns were reviewed. Monolithic silica columns prepared from tetraalkoxysilane
      by a sol-gel method showed high efficiency and high permeability on the basis of
      the small-sized silica skeletons, large-sized through-pores, and resulting
      through-pore size/skeleton size ratios much larger than those found in a particle
      packed column.

PMID- 12236536
TI  - Sweeping: concentration mechanism and applications to high-sensitivity analysis
      in capillary electrophoresis.
AB  - Sweeping in capillary electrophoresis (CE) involves the interaction of a
      pseudostationary phase (PS) in the separation solution and a sample in the matrix
      that is free of the PS used. The PS includes not only the PSs employed in
      electrokinetic chromatography, but also complexation reagents such as borate. The
      sample matrix could have a lower, similar, or higher conductance than the
      separation solution. Thus, the basic condition for sweeping is a sample matrix
      free of the additive. The accumulation of analyte molecules during the
      interaction makes this interesting phenomenon very useful as an on-line
      preconcentration method for CE. Preconcentration occurs due to chromatographic
      partitioning, complexation, or any interaction between analytes and PS. Contact
      between analyte and PS is facilitated by the action of electrophoresis and is
      independent of electroosmosis. The analyte, PS, or both should have
      electrophoretic velocities when an electric field is applied. The extent of
      preconcentration is dictated by the strength of the interaction involved. From
      tens to several thousand-fold improvements in detector response for many neutral
      and charged analytes have been achieved with this technique, suggesting sweeping
      as a general approach to on-line preconcentration in CE. The mechanism and
      applications of the sweeping phenomenon under different experimental conditions
      are discussed in this review, with particular emphasis on a better understanding
      of the sweeping mechanism under reduced electric field (high conductivity) in the
      sample zone.

PMID- 12236537
TI  - Comparison of conventional microparticulate and a monolithic reversed-phase
      column for high-efficiency fast liquid chromatography of basic compounds.
AB  - The effect of mobile phase flow on column efficiency for a neutral compound
      together with weak and strong bases was compared for conventional
      microparticulate (3/3.5 microm and 5 microm) silica RP columns and a monolithic
      silica RP. For benzene, the minimum plate height (Hmin) at optimum flow-rate
      (mu(opt)) for weak bases was similar for the 5 microm and the monolith phases.
      However, the monolith generated much flatter Van Deemter curves, such that at
      high flow-rate (5 ml min(-1)) the plate height was nearly 3.5 times lower on the
      monolith. For weak bases analysed in unbuffered mobile phases, and stronger bases
      with acid phosphate buffer, increased tailing was obtained on the monolith
      compared with the conventional phases. Nevertheless, Van Deemter plots on the
      monolith still showed some advantages over particulate phases, even when
      asymmetry factor was included in the calculation of the plate height. However, at
      pH 7 considerable tailing of strong bases was found using the monolith; it is not
      clear whether this results from unique features of the monolith structure, or
      whether it is due merely to usual problems of silica activity. Van Deemter plots
      for conventional phases may be improved considerably by operating the column at
      elevated temperatures. At pH 3, these improvements are influenced to a
      considerable extent by increases in Dm, as shown by measurements of Dm using the
      Taylor-Aris procedure. However, at pH 7.0, improvements are much too substantial
      to be explainable wholly on this basis.

PMID- 12236538
TI  - Hypercross-linked polystyrene and its potentials for liquid chromatography: a
      mini-review.
AB  - Hypercross-linked polymeric adsorbing materials are obtained under conditions
      that (i) their polymeric network is formed in the presence of large amounts of a
      thermodynamically good solvent (porogen) and (ii) the network is rigid.
      Hypercross-linked polystyrene is a transparent microporous low-density material
      with an apparent inner surface area of over 1,000 m2/g and an unprecedented
      adsorption capacity. To enhance the mass transfer, the adsorbent beads may be
      provided with large transport pores, in addition to the inherent micropores;
      these beads are opaque. Hypercross-linked polystyrene sorbents are widely used
      for large scale adsorption of organic compounds from aqueous and gaseous media
      and for solid-phase extraction of trace components. Novel perspective application
      areas of the materials are high-performance liquid chromatography column packings
      and blood purification. Present mini-review summarises basic principles of
      obtaining hypercross-linked materials, their structural peculiarities and
      distinguishing properties, as well as major application areas. Important new
      unpublished data are also included.

PMID- 12236539
TI  - Expressions for the C-term in the presence of pore flow.
AB  - In the course of our work on capillary electrochromatography (CEC) we, as others,
      have found strong evidence that flow in pores of particles can be significant.
      Its magnitude relative to the interstitial flow is characterized by the flow
      reduction factor, omega. Indirect evidence for pore flow was obtained much
      earlier by others, when it was noted that plate height, especially the C-term
      part, was significantly smaller in electrically driven (ED) than in pressure
      drive (PD) systems. This was interpreted as enhanced mass transfer, for which the
      intra-particle flow was held responsible. More direct evidence was produced by us
      when the size-exclusion (SEC) behaviour of polymers was studied in ED systems. It
      was found that the effect of exclusion on migration velocity could vanish
      entirely, and large and small molecules were co-eluted. This can only be
      explained if omega approaches 1; flow within the pores being as large as the
      interstitial flow. Indeed, consideration of double layer overlap indicated that
      omega-values close to 1 can often be expected in CEC. These large values omega
      inspired us to reconsider the effect of pore flow on the mass transfer term. We
      have arrived at the conclusion that enhanced mass transfer cannot explain in
      itself the extremely small values for the reduced plate height, h, (<1) observed
      especially for weakly retained solutes. In fact, when the pore flow is equal in
      magnitude to the interstitial flow, an unretained solute moves as fast within the
      particle as in the interstices; there is no non-equilibrium generated and a mass
      transfer term in h is not expected. For the migration of the solute the system is
      essentially uniform. Thus, apart from the mass transfer enhancement, another
      factor plays a role in the decrease of the h-values. We have attempted to derive
      a suitable expression for this effect. Some results are presented here. In one
      approach the situation is compared to that of an open tubular column with moving
      pseudo-stationary phase on the wall, an experiment that has actually been carried
      out by Krejci et al., or with micellar electrokinetic chromatography. In that
      case the plate height is easily derived. The result says that the plate height is
      proportional to the square of velocity difference between the two zones. However,
      the analogy is not perfect, and another approach suggests a direct
      proportionality rather than a square law one. Finally, a more refined treatment
      could be made only for a slab, not for a sphere. Extrapolation of this result to
      a sphere is put forward as a tentative expression for this effect.

PMID- 12236540
TI  - Capillary electrochromatography of proteins with polymer-based strong-cation
      exchanger microspheres.
AB  - Monodisperse poly(glycidyl methacrylate-divinylbenzene) microspheres were
      functionalized with propyl sulfonic acid moieties to obtain beads negatively
      charged in a wide pH range. They were packed into fused-silica capillary of 50
      micro, I.D. in order to separate proteins by capillary electrochromatography
      (CEC). Baseline separation of four basic proteins as well as three cytochrome c
      variants with an average column efficiency of 60,000 theoretical plates was
      obtained under isocratic elution conditions. The high efficiency is attributed to
      the uniformity of the column packing and the hydrophilic surface coverage of the
      polymer beads derived from the functionalization process. The effect of pH and
      salt concentration on protein separations was investigated and the results showed
      that the CEC separation mechanism is the combination of chromatographic retention
      and electrophoretic migration. Moreover, the column packed with the strongly
      acidic poly(glycidyl methacrylate-divinylbenzene) beads was also suitable for
      protein separations by micro-HPLC with a salt gradient. The comparison between
      the two kinds of elution modes shows that the column described here exhibited
      higher peak efficiency with isocratic elution in CEC than with gradient elution
      in micro-HPLC.

PMID- 12236541
TI  - Predicting the behaviour of polydisperse polymers in liquid chromatography under
      isocratic and gradient conditions.
AB  - In this paper we describe how the existing theories to describe retention and
      peak width in isocratic and gradient-elution liquid chromatography can be
      expanded to describe the retention behaviour of natural and synthetic repetitive
      polymers, which feature distributions of molecules with different masses (and
      often different structures) rather than unambiguous molecular formulas. For
      polydisperse samples, it is vital that the model accommodates (isocratic) elution
      of sample components before the onset of a gradient, elution during the gradient,
      and elution after the completion of the gradient. The expanded models can readily
      be implemented in standard spreadsheet software, such as Excel. We have created
      such spreadsheets based on the conventional model for retention in reversed-phase
      liquid chromatography (RPLC) and on two different models for retention in normal
      phase liquid chromatography. The implementation allows an easy visualization of
      the theoretical concept. Up to three different polymeric series can be entered,
      with a total of up to 100 peaks being computed and displayed in isocratic or
      gradient-elution chromatograms. Also visualized are "retention models" (diagrams
      of isocratic retention vs. composition) and "calibration curves" (retention or
      elution composition vs. molecular mass or degree of polymerization). The
      coefficients in the isocratic retention model may be correlated, as has often
      been observed in RPLC. It is shown that under certain conditions such a
      correlation corresponds to the existence of so-called critical (isocratic)
      conditions, at which all the members of a given polymeric series (same
      composition and end groups, different number of repeat units) show co-elution.

PMID- 12236543
TI  - A novel sheep model to study the effect of high rate intracoronary perfusion on
      cardiac electrophysiology.
AB  - An increase in coronary flow is known to enhance myocardial metabolism and
      contractility (the Gregg effect) but the effect on cardiac electrophysiology is
      unclear. In 5 pentobarbital-anesthetised open-chest sheep, left circumflex
      coronary artery was perfused with fresh arterial blood at 6 and 10 ml/min
      respectively in the presence of normal coronary flow. The perfusion was repeated
      in these animals after treatment with nitro-L-arginine, a nitric oxide synthase
      inhibitor. The high rate intracoronary perfusion caused a flow-dependent T wave
      inversion on body surface ECG in all animals (p < 0.01). Pre-treatment with nitro
      L-arginine abolished T wave inversion during 6 ml/min perfusion, and diminished
      the T inversion during 10 ml/min perfusion. CONCLUSION: An increase in coronary
      flow alters ventricular repolarisation through nitric oxide release from coronary
      endothelium.

PMID- 12236542
TI  - Volume osmotic flows of non-homogeneous electrolyte solutions through
      horizontally mounted membrane.
AB  - Results of an experimental study of volume osmotic flows in a single-membrane
      osmotic-diffusive cell, which contains a horizontal, microporous, symmetrical
      polymer membrane separating water and binary or ternary electrolyte solutions are
      presented. In the experimental set-up, water was placed on one side of the
      membrane. The opposite side of the membrane was exposed to binary or ternary
      solutions. As binary solutions, aqueous potassium chloride or ammonia solutions
      were used, whereas potassium chloride in 0.25 mol x l(-1) aqueous ammonia
      solution or ammonia in 0.1 mol x l(-1) aqueous potassium chloride solution were
      used as ternary solutions. Two (A and B) configurations of a single-membrane
      osmotic-diffusive cell in a gravitational field were studied. In configuration A,
      water was placed in a compartment above the membrane and the solution below the
      membrane. In configuration B the position of water and solution was reversed.
      Furthermore, the effect of amplification of volume osmotic flows of electrolyte
      solutions in the single-membrane osmotic-diffusive electrochemical cell was
      demonstrated. The thermodynamic models of the flux graviosmotic and amplification
      effects were developed, and the volume flux graviosmotic effect for
      configurations A and B of a single-membrane osmotic-diffusive cell was
      calculated. The results were interpreted within the conventional instability
      category, increasing the diffusion permeability coefficient value for the system:
      concentration boundary layer/membrane/concentration boundary layer.

PMID- 12236544
TI  - In vitro and in vivo assessment of the antioxidant activity of melatonin and
      related indole derivatives.
AB  - Effects of melatonin and some structurally related indole compounds were studied
      by in vitro methods such as (i) an inhibition of the hyaluronic acid degradation
      and (ii) a standard lipid peroxidation assay. In vivo approach was based on the
      alloxan model of hyperglycaemia. Reduction of the viscosity of a hyaluronic acid
      solution in the reaction mixture was inhibited by tryptamine (91% inhibition), as
      well as by indole-3-carboxylic acid and indomethacin (80% and 77% inhibition,
      respectively). Lipid peroxidation with tert-butyl hydroperoxide as a source of
      radicals was followed by the formation of thiobarbituric acid reactive
      substances. Tested drugs inhibited lipid peroxidation in the order: tryptamine
      (59%) > indole-2-carboxylic acid (38%) > indomethacin (26%) > melatonin and
      indole-3-carboxylic acid (13%). In vivo, alloxan-induced hyperglycaemia was
      reduced in mice pretreated with drugs tested. The highest protective effect was
      observed with indomethacin (52% inhibition), followed by tryptamine and melatonin
      (18% and 16% inhibition, respectively).

PMID- 12236546
TI  - Effect of polyanion on the acidic conformational transition of native and
      denatured ferricytochrome c. Circular dichroism study.
AB  - Interaction of polyanion poly(vinylsulfate) with oxidized cytochrome c (cyt c)
      significantly affects the protein main characteristics. One of them, pKa value of
      acidic transition, was shifted from an apparent pKa value 2.5 (typical for cyt c
      in low ionic strength solvent) to approximately 5.20 +/- 0.15 upon polyanion
      binding to the protein, pointing to a likely involvement of histidines 26 and/or
      33 in the protein acidic transition in complex with the polyanion. The acidic
      transition followed at 6 different wavelengths all over circular dichroism
      spectrum, monitoring different parts of the protein structure, revealed basically
      two-state character process. Only ellipticity at 262 nm indicated a low
      cooperative pH-induced conformational transition in heme region with an apparent
      pKa approximately 4.34 +/- 0.25 in accordance with absorbance change at 620 nm.
      Polyanion also interacts with chemically-denatured (in the presence of 9 mol/l
      urea) state of the protein as it follows from stabilization of protein residual
      structure at acidic pH and its effect on pKa value of acidic transition of
      chemically-denatured cyt c. Destabilization effect of polyanions on native and,
      on the other hand, stabilization influence on partially unfolded conformations of
      the protein are discussed with an implication for their chaperone-like properties
      in vivo and in vitro.

PMID- 12236545
TI  - Neuronal nitric oxide synthase in the rabbit spinal cord visualised by
      histochemical NADPH-diaphorase and immunohistochemical NOS methods.
AB  - The NADPH-diaphorase (NADPH-d) staining method is widely used in the
      investigation of both the central and peripheral nervous systems. Neuronal nitric
      oxide synthase (nNOS) has previously been shown to be responsible for the NADPH-d
      activity in neurons. However, NADPH-d activity does not always fully represent
      the enzyme nNOS. We investigated the distribution of NADPH-d activity and nNOS
      protein in the rabbit spinal cord for all groups of neurons and Rexed's laminae.
      In most laminae the distribution of NADPH-d activity was identical to nNOS
      immunoreactivity. Both were present in the dorsal horn and in pericentral areas
      of the spinal cord, but some differences existed. The superficial part of the
      dorsal horn (laminae I-III) stained more intensely for NADPH-d than for nNOS.
      However, the most prominent difference was seen in the lateral part of the dorsal
      horn--the lateral collateral pathway (LCP). The LCP stained strongly for NADPH-d
      activity, while nNOS staining was absent. Although there is an excellent
      correlation between NADPH-d staining and nNOS immunohistochemical staining in the
      spinal cord in general, the presence of staining differences necessitates the use
      of immunohistochemistry for some specialized applications.

PMID- 12236548
TI  - Nitric oxide synthase inhibitor L-NAME has no effect on 86Rb accumulation in rat
      renal cortical slices.
AB  - The aim of present study was to investigate the effect of the nitric oxide
      synthase inhibitor L-NAME on the 86Rb uptake in rat renal cortical slices. Rats
      were divided into three groups: 1. CONTROL. 2. Acute: L-NAME (10 mg/kg i.v.) as a
      bolus 15 min before the excision of the kidneys. 3. Sub-chronic: L-NAME (10
      mg/kg/day) per os for 4 days. Renal cortical slices were incubated for 10, 20,
      30, 60, 90, 180 seconds in Krebs-Ringer solution containing 50 kBq 86Rb/100 ml (T
      = 37 degrees C, PO2 approximately 159 mm Hg). 56Rb accumulation (S/M) was
      calculated as the ratio of the radioactivity of the cortical slices (S) and the
      radioactivity of the incubating medium (M). The S/M ratio can be described as a
      function of time by the following equations. CONTROL: y = 0.265 ln(x) - 0.220,
      r(xy) = 0.886; acute L-NAME: y = 0.224 ln(x) - 0.171, r(xy) = 0.921; sub-chronic
      L-NAME: y = 0.331 ln(x) - 0.496, r(xy) = 0.942. (y = S/M, x = t). p < 0.001 in
      all of the groups, but there is no difference between the groups. In conclusion,
      L-NAME administered in vivo failed to influence the in vitro 86Rb accumulation in
      rat renal cortical slices.

PMID- 12236547
TI  - Effects of carvedilol and BL-443 on kidney of rats with cyclosporine nephropathy.
AB  - Effects of cyclosporine A on kidneys of rats and the effects of carvedilol or BL
      443 on kidneys of rats with cyclosporine nephropathy were studied. Male rats
      (Wistar) were divided into four groups (n = 7). Three groups of rats were treated
      in single oral daily doses of 45 mg cyclosporine A/kg body weight to cause
      cyclosporine nephropathy. Two of the treated groups were then medicated either
      with carvedilol or BL-443 in single daily doses of 10 mg/kg b.w., and 1 ml doses
      of saline were given daily i.p. to the third group of rats. Animals were treated
      and medicated for 17 days. The rats of intact group had no treatment and
      medication. L-lactate dehydrogenase isoenzymes LD(1-4) in the kidney extracts
      were determined by polyacrylamide gel clectrophoresis. Significant differences of
      LD(1-4) pattern in kidneys between intact rats and each of the three groups of
      rats with cyclosporine nephropathy were found by F-test and t-test (p < 0.05).
      Treatment with cyclosporine A affected the LD(1-4) pattern in kidneys. On the
      other hand, no significant differences of LD(1-4) pattern in kidneys between rats
      with non-treated cyclosporine nephropathy and rats with cyclosporine nephropathy
      medicated with carvedilol or BL-443 were found.

PMID- 12236549
TI  - Firing properties of the soma and axon of the abdominal stretch receptor neurons
      in the crayfish (Astacus leptodactylus).
AB  - Action potentials (APs) and impulse responses in the soma and axon of the rapidly
      and slowly adapting (SA) abdominal stretch receptor neurons of the crayfish
      (Astacus leptodactylus) were recorded with single microelectrode current-clamp
      technique. Impulse frequency response to constant current injection was almost
      constant in the SA neuron while the response decayed completely in the rapidly
      adapting (RA) neuron. Mean impulse frequency responses to current stimulations
      were similar in the receptor neuron pairs. In the RA neuron additional current
      steps evoked additional impulses while a sudden drop in the current amplitude
      caused adaptation. Impulse duration was dependent on the rate of rise when
      current ramps were used. Adaptation was facilitated when calculated receptor
      current was used. Exposing the neuron to 3 mmol/l TEA or scorpion venom resulted
      in partly elongated impulse responses. SA neuron could continuously convert the
      current input into impulse frequency irrespective of previous stimulation
      conditions. Exposing the SA neuron to 3 mmol/l TEA or 1 mmol/l Lidocaine reduced
      impulse duration to large current stimulations. The SA neuron fired spontaneously
      if it was exposed to 5-10 mmol/l Lidocaine or 10(-2) mg/ml Leiurus
      quinquestriatus venom. The action potential (AP) amplitudes in the RA soma, RA
      axon, SA soma, and SA axon were significantly different between components of all
      pairs. Duration of the AP in the axon of the RA neuron was significantly shorter
      than those in the RA soma, SA soma, and SA axon. Diameter of the RA axon was
      larger than that of the SA axon. Non-adapting impulse responses were promptly
      observed only in the SA axons. The results indicate that the RA neuron is a sort
      of rate receptor transducing the rapid length changes in the receptor muscle
      while the SA neuron is capable of transducing the maintained length changes in
      the receptor muscle. The differences in firing properties mainly originate from
      the differences in the active and passive properties of the receptor neurons.

PMID- 12236550
TI  - Humic colloid-borne migration of uranium in sand columns.
AB  - Column experiments were carried out to investigate the influence of humic
      colloids on subsurface uranium migration. The columns were packed with well
      characterized aeolian quartz sand and equilibrated with groundwater rich in humic
      colloids (dissolved organic carbon (DOC): 30 mg dm(-3)). U migration was studied
      under an Ar/1% CO2 gas atmosphere as a function of the migration time, which was
      controlled by the flow velocity or the column length. In addition, the contact
      time of U with groundwater prior to introduction into a column was varied. U(VI)
      was found to be the dominant oxidation state in the spiked groundwater. The
      breakthrough curves indicate that U was transported as a humic colloid-borne
      species with a velocity up to 5% faster than the mean groundwater flow. The
      fraction of humic colloid-borne species increases with increasing prior contact
      time and also with decreasing migration time. The migration behavior was
      attributed to a kinetically controlled association/dissociation of U onto and
      from humic colloids and also a subsequent sorption of U onto the sediment
      surface. The column experiments provide an insight into humic colloid-mediated U
      migration in subsurface aquifers.

PMID- 12236551
TI  - Transverse vertical dispersion in groundwater and the capillary fringe.
AB  - Transverse dispersion is the most relevant process in mass transfer of
      contaminants across the capillary fringe (both directions), dilution of
      contaminants, and mixing of electron acceptors and electron donors in
      biodegrading groundwater plumes. This paper gives an overview on literature
      values of transverse vertical dispersivities alpha(tv) measured at different flow
      velocities and compares them to results from well-controlled laboratory-tank
      experiments on mass transfer of trichloroethene (TCE) across the capillary
      fringe. The measured values of transverse vertical dispersion in the capillary
      fringe region were larger than in fully saturated media, which is credited to
      enhanced tortuosity of the flow paths due to entrapped air within the capillary
      fringe. In all cases, the values observed for alpha(tv) were << 1 mm. The new
      measurements and the literature values indicate that alpha(tv) apparently
      declines with increasing flow velocity. The latter is attributed to incomplete
      diffusive mixing at the pore scale (pore throats). A simple conceptual model,
      based on the mean square displacement and the pore size accounting for only
      partial diffusive mixing at increasing flow velocities, shows very good agreement
      with measured and published data.

PMID- 12236552
TI  - Push-pull partitioning tracer tests using radon-222 to quantify non-aqueous phase
      liquid contamination.
AB  - Naturally occurring radon in groundwater can be used as an in situ partitioning
      tracer for locating and quantifying non-aqueous phase liquid (NAPL) contamination
      in the subsurface. When combined with the single-well, push-pull test, this
      methodology has the potential to provide a low-cost alternative to inter-well
      partitioning tracer tests. During a push-pull test, a known volume of test
      solution (radon-free water containing a conservative tracer) is first injected
      ("pushed") into a well; flow is then reversed and the test solution/groundwater
      mixture is extracted ("pulled") from the same well. In the presence of NAPL radon
      transport is retarded relative to the conservative tracer. Assuming linear
      equilibrium partitioning, retardation factors for radon can be used to estimate
      NAPL saturations. The utility of this methodology was evaluated in laboratory and
      field settings. Laboratory push-pull tests were conducted in both non
      contaminated and trichloroethene NAPL (TCE)-contaminated sediment. The
      methodology was then applied in wells located in non-contaminated and light non
      aqueous phase liquid (LNAPL)-contaminated portions of an aquifer at a former
      petroleum refinery. The method of temporal moments and an approximate analytical
      solution to the governing transport equations were used to interpret breakthrough
      curves and estimate radon retardation factors; estimated retardation factors were
      then used to calculate TCE saturations. Numerical simulations were used to
      further investigate the behavior of the breakthrough curves. The laboratory and
      field push-pull tests demonstrated that radon retardation does occur in the
      presence of TCE and LNAPL and that radon retardation can be used to calculate TCE
      saturations. Laboratory injection-phase test results in TCE-contaminated sediment
      yielded radon retardation factors ranging from 1.1 to 1.5, resulting in
      calculated TCE saturations ranging from 0.2 to 0.9%. Laboratory extraction-phase
      test results in the same sediment yielded a radon retardation factor of 5.0, with
      a calculated TCE saturation of 6.5%. Numerical simulation breakthrough curves
      provided reasonably good matches to the approximate analytical solution
      breakthrough curves. However, non-equilibrium radon partitioning and
      heterogeneous TCE distributions may affect the retardation factors and TCE
      saturation estimates.

PMID- 12236553
TI  - Bench-scale visualization of DNAPL remediation processes in analog heterogeneous
      aquifers: surfactant floods and in situ oxidation using permanganate.
AB  - We have conducted well-controlled DNAPL remediation experiments within a 2-D,
      glass-walled, sand-filled chamber using surfactants (Aerosol MA and Tween 80) to
      increase solubility and an oxidant (permanganate) to chemically degrade the
      DNAPL. Initial conditions for each remediation experiment were created by
      injecting DNAPL as a point source at the top of the chamber and allowing the
      DNAPL to migrate downward through a water-filled, heterogeneous, sand-pack
      designed to be evocative of a fluvial depositional environment. This migration
      process resulted in the DNAPL residing as a series of descending pools. Lateral
      advection across the chamber was used to introduce the remedial fluids.
      Photographs and digital image analysis illustrate interactions between the
      introduced fluids and the DNAPL. In the surfactant experiments, we found that
      DNAPL configured in a series of pools was easily mobilized. Extreme reductions in
      DNAPL/water interfacial tension occurred when using the Aerosol MA surfactant,
      resulting in mobilization into low permeability regions and thus confounding the
      remediation process. More modest reductions in interfacial tension occurred when
      using the Tween 80 surfactant resulting in modest mobilization. In this
      experiment, capillary forces remained sufficient to exclude DNAPL migration into
      low permeability regions allowing the excellent solubilizing properties of the
      surfactant to recover almost 90% of the DNAPL within 8.6 pore volumes. Injection
      of a potassium permanganate solution resulted in precipitation of MnO2, a
      reaction product, creating a low-permeability rind surrounding the DNAPL pools.
      Formation of this rind hindered contact between the permanganate and the DNAPL,
      limiting the effectiveness of the remediation. From these experiments, we see the
      value of performing visualization experiments to evaluate the performance of
      proposed techniques for DNAPL remediation.

PMID- 12236554
TI  - Using polymer solutions to enhance recovery of mobile coal tar and creosote
      DNAPLs.
AB  - Direct pumping and enhanced recovery of coal tar and creosote dense, non-aqueous
      phase liquids (DNAPLs) from the subsurface have had mixed results because these
      DNAPLs are viscous fluids that can potentially alter aquifer wettability. To
      improve the inefficiencies associated with waterflooding, the research presented
      here considered the use of a polymer solution that can be added to the injected
      flood solution to increase the viscosity and decrease the velocity of the
      flooding solution. Results from one-dimensional, vertically oriented laboratory
      column experiments that evaluate the recovery of coal-derived DNAPL with both
      water and polymer flooding solutions are presented. The final DNAPL saturation
      remaining in the column was assessed in water and oil-wet systems for three
      viscous DNAPLs. Adding polymer to increase the aqueous solution viscosity did not
      have a significant impact in water-wet systems. A final DNAPL saturation of
      approximately 19% was achieved for both water and polymer floods. In contrast,
      the addition of polymer significantly improved recovery in oil-wet systems. The
      final saturation was over 40% in oil-wet systems after waterflooding, but
      approximately 19% with a polymer flushing solution. Although the final saturation
      produced with polymer flooding was similar between the oil- and water-wet
      systems, differences in the relative permeability and distribution of DNAPL in
      the porous matrix caused the DNAPL recovery to be much slower in the oil-wet
      system.

PMID- 12236555
TI  - Experimental determination of sorption in fractured flow systems.
AB  - Fracture "skins" are alteration zones on fracture surfaces created by a variety
      of biological, chemical, and physical processes. Skins increase surface area,
      where sorption occurs, compared to the unaltered rock matrix. This study examines
      the sorption of organic solutes on altered fracture surfaces in an experimental
      fracture-flow apparatus. Fracture skins containing abundant metal oxides, clays,
      and organic material from the Breathitt Formation (Kentucky, USA) were collected
      in a manner such that skin surface integrity was maintained. The samples were
      reassembled in the lab in a flow-through apparatus that simulated approximately
      2.7 m of a linear fracture "conduit." A dual-tracer injection scheme was utilized
      with the sorbing or reactive tracer compared to a non-reactive tracer (chloride)
      injected simultaneously. Sorption was assessed from the ratio of the first
      temporal moments of the breakthrough curves and from the loss of reactive tracer
      mass and evaluated as a function of flow velocity and solute type. The
      breakthrough curves suggest dual-flow regimes in the fracture with both sorbing
      and non-sorbing flow fields. Significant sorption occurs for the reactive
      components, and sorption increased with decreasing flow rate and decreasing
      compound solubility. Based on moment analysis, however, there was little
      retardation of the center of solute mass. These data suggest that non-equilibrium
      sorption processes dominate and that slow desorption and boundary layer diffusion
      cause extensive tailing in the breakthrough curves.

PMID- 12236556
TI  - A proposed model to include a residual NAPL saturation in a hysteretic capillary
      pressure-saturation relationship.
AB  - A residual non-aqueous phase liquid (NAPL) present in the vadose zone can act as
      a contaminant source for many years as the compounds of concern partition to
      infiltrating groundwater and air contained in the soil voids. Current pressure
      saturation-relative permeability relationships do not include a residual NAPL
      saturation term in their formulation. This paper presents the results of series
      of two- and three-phase pressure cell experiments conducted to evaluate the
      residual NAPL saturation and its impact on the pressure-saturation relationship.
      A model was proposed to incorporate a residual NAPL saturation term into an
      existing hysteretic three-phase parametric model developed by Parker and Lenhard
      [Water Resour. Res. 23(12) (1987) 2187], Lenhard and Parker [Water Resour. Res.
      23(12) (1987) 2197] and Lenhard [J. Contam. Hydrol. 9 (1992) 243]. The
      experimental results indicated that the magnitude of the residual NAPL saturation
      was a function of the maximum total liquid saturation reached and the water
      saturation. The proposed model to incorporate a residual NAPL saturation term is
      similar in form to the entrapment model proposed by Parker and Lenhard, which was
      based on an expression presented by Land [Soc. Pet. Eng. J. (June 1968) 149].

PMID- 12236557
TI  - Respiratory syncytial virus infections--an underdiagnosed entity?

PMID- 12236558
TI  - Seasonality of respiratory syncytial virus-positive hospitalizations in children
      in Kiel, Germany, over a 7-year period.
AB  - BACKGROUND: Elaborate, long-term data on the rhythm, seasonality and severity of
      the yearly respiratory syncytial virus (RSV) epidemics in Germany are lacking.
      PATIENTS AND METHODS: A longitudinal investigation was undertaken of children
      from birth to 16 years of age admitted with an RSV infection in the two pediatric
      hospitals in Kiel between July 1994 and June 2001. To compare the severity of the
      individual seasons, the incidences and the proportion of RSV-positive
      hospitalized children aged 0 to 2 years from the denominator area of Kiel were
      compared. RESULTS: During the 7-year period, the nasopharyngeal aspirates of
      2,367 children were investigated; RSV was detected in 384 (16.2%). The seasons
      from 1994/95 to 1996/97 started late (December to January) and ended between
      March and May. Since 1997/98 it seems that a late season is followed by an early
      season (start in September to October) in a 2-year pattern. CONCLUSION: No fixed
      rhythm of the RSV season can be identified as yet. Ascertainment bias is unlikely
      to explain the differences in rhythm. The incidence of RSV-positive
      hospitalizations seems to be increasing.

PMID- 12236559
TI  - The impact of respiratory syncytial virus infection: a prospective study in
      hospitalized infants younger than 2 years.
AB  - BACKGROUND: We analyzed the influence of respiratory syncytial virus (RSV) on the
      clinical course and management of infants hospitalized due to viral upper and
      lower respiratory tract infections (U/LRTI). PATIENTS AND METHODS: Infants
      younger than 2 years were prospectively tested for RSV infection by antigen
      detection in nasopharyngeal aspirates between November 1999 and October 2000.
      RESULTS: Of 281 infants hospitalized during the study period, 58 (21%) tested RSV
      positive. Seasonal distribution of RSV infections showed a peak in March (45% of
      all U/LRTI). Infants with RSV infection (12% were preterm, 5% had congenital
      heart disease) were younger (p < 0.001), had more severe U/LRTI (p < 0.001),
      longer hospitalizations (p < 0.001), more days with oxygen requirement (p <
      0.001) and respiratory support (p = 0016) and more frequent requirements for
      bronchodilators (p = 0.002) and corticosteroids (p = 0.02). CONCLUSION: RSV
      contributed to prolonged hospitalizations and more severe clinical courses of
      disease both in very young term and preterm infants.

PMID- 12236560
TI  - Occurrence of methicillin-resistant Staphylococcus aureus infections in German
      intensive care units.
AB  - BACKGROUND: This study aims to describe the occurrence of nosocomial methicillin
      resistant Staphylococcus aureus (MRSA) infections and the relation between
      endemic and epidemic nosocomial MRSA infections in intensive care units (ICUs) in
      Germany. METHODS: The ICU component within the German national nosocomial
      infections surveillance system (KISS) was established in January 1997. The number
      of participating ICUs increased from 25 in 1997 to 178 (June 2000). In every case
      of nosocomial infection (NI), the pathogens identified were referred to the
      surveillance system. To identify clusters and outbreaks and distinguish them from
      mere single events, the following simple definitions were applied: a "cluster"
      was two nosocomial MRSA infections within 3 months; an "outbreak" was three or
      more nosocomial MRSA infections within 3 months; all other MRSA infections were
      classed as "single events." RESULTS: A total of 10,261 NIs were identified during
      the observation period in the 139 ICUs which had been participating for at least
      6 months. Among the 1,535 nosocomial S. aureus infections, 219 MRSA infections
      were identified (14.3%). Only 51 (36.7%) of the 139 KISS ICUs identified
      nosocomial MRSA infections. In 12 ICUs (8.6%) however, more than 50% of all
      nosocomial S. aureus infections were caused by MRSA. The mean incidence density
      was 0.31 nosocomial MRSA infections/1,000 patient days (range 0-3.6). Outbreaks
      were registered in 13 ICUs, clusters in 12 further ICUs and only single events in
      the remaining 26. 64.0% of all MRSA infections were registered during outbreaks
      and 12.8% in cluster situations. Thus, only 23.2% of MRSA infections were single
      events. CONCLUSION: These definitions of clusters and outbreaks can only provide
      an estimate of the real number of cases. However, through the targeted
      identification of ICUs with endemic and epidemic MRSA problems and subsequent
      strict measures to prevent the spread of MRSA within these ICUs, it may be
      possible to retain, or even reduce, the present level of MRSA infections in
      Germany.

PMID- 12236561
TI  - Respiratory symptoms, asthma, atopy and Chlamydia pneumoniae IgG antibodies in a
      general population sample of young adults.
AB  - BACKGROUND: This study was designed to test the association of Chlamydia
      pneumoniae infection with respiratory symptoms and atopy. METHODS: A general
      population sample of 369 young adults (aged 20-44 years) completed a
      questionnaire on respiratory symptoms and underwent skin prick testing. C.
      pneumoniae IgG and IgM serum titers were measured by microimmunofluorescence.
      Prior infection was defined by titers of IgG > or = 1:32, acute infection by
      titers of IgG > or = 1:512 and/or IgM > or = 1:16. RESULTS: The prevalence of
      cough and phlegm was higher in subjects with (19.0%) than in those without
      (11.4%) prior C. pneumoniae infection (p = 0.01). A similar difference was found
      for wheezing (14.3% vs 8.0%; p = 0.05), whereas the percentage of asthmatics was
      equally distributed between seropositive and seronegative subjects. IgG titers >
      or = 1:128 were found more frequently in atopic subjects (p = 0.04). After
      adjusting for any confounding factors, cough and phlegm (but not wheezing) were
      found significantly associated with C. pneumoniae positivity, both for 1:32 (OR
      1.80; 95% CI: 1.01-3.36; p = 0.05) and for 1:128 titers (OR 2.31; 95% CI: 1.20
      4.42; p = 0.01). A significant association was also found for atopy, for titers >
      or = 1:128 (OR 1.73; 95% CI: 1.01-3.20, p = 0.05). Acute infection was not
      associated with respiratory symptoms or asthma. CONCLUSION: We conclude that C.
      pneumoniae infection is associated with cough and phlegm and may have a role in
      the pathogenesis of chronic respiratory diseases. Moreover, our results indicate
      a relationship between atopy and C. pneumoniae infection.

PMID- 12236562
TI  - Influence of moxifloxacin, comparator drugs and some fractions of pulmonary
      surfactant on adherence of some respiratory pathogens.
AB  - BACKGROUND: This study evaluated the effect of moxifloxacin and comparator drugs
      with or without some fractions of pulmonary surfactant, as surfactant protein-A
      (SP-A) and phospholipids, on the adherence of the most common respiratory
      pathogens. MATERIALS AND METHODS: The adherence of respiratory pathogens to a
      bronchial epithelial cell line was tested. Antimicrobials were used at 1/2, 1/4
      and 1/8 minimum inhibitory concentration (MIC), SP-A at 1 and 5 microg/ml and
      phospholipids at 50 microg/ml. RESULTS: At 1/2 MIC moxifloxacin, ciprofloxacin,
      amoxicillin-clavulanate and ceftriaxone reduced the adherence of Staphylococcus
      aureus and Streptococcus pneumoniae to values of 40-50%. At the same
      concentration, cotrimoxazole reduced the adherence values of Moraxella
      catarrhalis and Haemophilus influenzae to about 50%, while beta-lactams showed
      high efficacy only on H. influenzae, with adherence values of about 40%. The
      addition of SP-A and/or phospholipids to the tested antibiotics had no effect on
      bacterial adherence. CONCLUSION: The non-interference of SP-A and/or
      phospholipids with the suppressive effect that some antibiotics exert on
      bacterial adherence could represent a favorable event during antibiotic therapy.

PMID- 12236563
TI  - Endocarditis after urinary tract infection.

PMID- 12236564
TI  - Immunity to poliomyelitis: situation in northern Italy and in some other European
      population groups.
AB  - The aim of the program to eradicate poliomyelitis is expected to be achieved in
      the space of very few years and therefore, as they approach this goal, countries
      find themselves faced with various problems to be tackled. Among these is the
      decision about how and when to stop polio vaccination, which also depends on
      seroepidemiological evaluations, necessary because of the possible persistence of
      circulating strains of poliovirus of vaccine origin which might continue even
      after the suspension of vaccination. For this reason, the results of
      seroepidemiological surveys carried out in some European countries in different
      periods of time and on various samples of the population are discussed. Although
      the status of immune coverage is satisfactory, a few situations of susceptibility
      were found; these should be better monitored and, if necessary, corrected to
      guarantee a homogeneous and lasting resistance of the European population towards
      polioviruses.

PMID- 12236565
TI  - A critical review of control strategies against meningococcal meningitis
      epidemics in sub-Saharan African countries.
AB  - The control strategy of meningitis epidemics in sub-Saharan countries, although
      reexamined regularly, is based on epidemiological, immunological and logistical
      considerations put forward at the end of the 1970s. It comprises organizing large
      scale vaccinations in the event of a declared epidemic. The obvious failure of
      this strategy recommended by the World Health Organization (WHO) necessitates
      evaluation of the emergency vaccination criteria. Despite current controversy on
      the immunogenicity of the polysaccharide vaccine, its safety, effectiveness in
      the field and low cost could justify the reopening of a debate on its use in
      routine vaccination. Routine--or preventive--vaccination could significantly
      reduce the incidence of meningococcal meningitis and its severity. The conjugate
      vaccine, when available, will constitute an additional advantage in the
      prevention of meningococcal meningitis. A strategy combining both polysaccharide
      and conjugate vaccines according to the population targets and possibilities for
      funding remain to be defined.

PMID- 12236566
TI  - Travel-acquired dengue infection: clinical spectrum and diagnostic aspects.
AB  - BACKGROUND: Dengue fever is increasingly recognized in travelers returning from
      endemic areas with acute febrile illness; however, its true burden in nonendemic
      countries is unknown. Only few studies focus on clinical manifestations and
      serological findings in primarily nonimmune individuals. PATIENTS AND METHODS: We
      analyzed the epidemiology, clinical manifestations and virological results in
      patients with imported acute dengue infection who presented at our travel clinic
      in Frankfurt am Main, Germany, between September 1998 and November 2000. An
      immunochromatographic test and an immunofluorescence assay were used for antibody
      testing. RESULTS: Dengue fever was confirmed in 13 patients, thus being the
      second commonest tropical infection after malaria in patients with fever and a
      travel history to a tropical country (18 cases per 1,000 patient visits per
      year). Most patients had only spent a short time abroad, either in South Central
      or South East Asia or in the Caribbean. CONCLUSION: The clinical features
      considered typical for dengue were not always present. Antibody assays were
      typically negative early in the course of disease, with seroconversion occurring
      only after cessation of clinical symptoms. A high index of suspicion is needed in
      these patients who often present without typical features of dengue and whose
      early antibody tests may be negative.

PMID- 12236567
TI  - Keratoconjunctivitis sicca and chronic HCV infection.
AB  - BACKGROUND: The aim of this study was to determine the prevalence of
      keratoconjunctivitis sicca (KCS) in Greek patients with chronic hepatitis C virus
      (HCV) infection and its association with HCV genotypes and liver histology.
      PATIENTS AND METHODS: 93 HCVAb (+) patients underwent lacrimal function testing
      (Schirmer-1 test, break-up time test and Rose-Bengal staining test) and
      estimation of serum cryoglobulins and autoantibodies. 80 healthy volunteers were
      included in the study as controls. RESULTS: 34 out of 93 HCV patients (36.6%) and
      eight out of 80 healthy subjects (10%) had at least two abnormal lacrimal
      function tests suggestive of KCS (p < 0.001), cryoglobulinemia was evident in 20
      patients (21.5%), rheumatoid factor (RF) in 43 (46.2%), antinuclear antibodies
      (ANA) in 19 (20.4%), antinuclear antigens (anti-SS-A and anti-SS-B) in one (1.1%)
      and two (2.2%) patients, respectively. Reduced prevalence of KCS was found in
      patients with genotype 3a compared to those with other genotypes (5/30, 16.7% vs
      20/42, 47.6%, p = 0.007), probably because of their younger age. In patients with
      KCS a higher staging score was noted in liver biopsy compared to those without
      KCS (4.50 +/- 1.65 vs 3.06 +/- 1.88, p = 0.005). CONCLUSION: Greek patients with
      chronic HCV infection have a high prevalence of KCS (36.6%). The low frequency of
      anti-SS-A and anti-SS-B antibodies in these patients denotes different
      pathogenetic associations from primary Sjogren's syndrome.

PMID- 12236568
TI  - Herpetic whitlow infection in a general pediatrician--an occupational hazard.
AB  - Herpetic whitlow is a well-known occupational hazard for medical staff. It has
      been reported to affect mainly workers in intensive care units who come into
      close contact with oral secretions. We report herpetic whitlow infection in a
      general pediatrician in order to increase the awareness to this infectious
      occupational hazard that might occur in any health care worker who deals with
      oral secretions. A 35-year-old male general pediatrician sustained a minor knife
      cut in his finger and 5 days later he developed herpetic whitlow. He was treated
      with acyclovir with gradual improvement. We review the clinical course,
      complications and treatment of herpetic whitlow. The source of the infection in
      the present case was unknown, but it probably derived from oral secretions of
      children with unrecognized infection. Simple measures like wearing gloves during
      oral examination will avoid unnecessary morbidity in medical staff.

PMID- 12236569
TI  - Isolation of dengue virus serotype 1 from the blood of a Swiss traveler prior to
      seroconversion.
AB  - Dengue virus serotype 1 was isolated from the blood of a patient who had returned
      to Switzerland from Brazil with fever of unknown origin. After 2 days of culture
      on Aedes albopictus (C6/36) cell line, the dengue virus was identified as
      serotype 1 using a type-specific indirect immunofluorescence assay. The diagnosis
      was confirmed by seroconversion of anti-dengue virus-specific IgM and IgG
      antibodies and by amplification of a serotype 1-specific region of the dengue
      virus genome. This is the first description of dengue virus isolation from the
      blood of a traveler returning to Switzerland. We recommend detection of dengue
      viremia during the 1st week of illness, before serological tests usually yield
      conclusive results, as the most efficient means of early specific diagnosis.

PMID- 12236570
TI  - Eikenella corrodens brain abscess after repeated periodontal manipulations cured
      with imipenem and neurosurgery.
AB  - Eikenella corrodens is a facultatively anaerobic gram-negative rod that colonizes
      the oral cavity and very rarely produces central nervous system (CNS) infections.
      Frontal lobe abscesses are occasionally associated with a dental source of
      infection. We report a case of an adult man with overzealous dental cleaning
      habits who developed a right frontal brain abscess caused by E. corrodens. He
      underwent neurosurgical drainage of the pus and was successfully treated with
      imipenem 4 g/i.v./day for 4 weeks with no complications. Repeated periodontal
      trauma could explain the Eikenella brain abscess in this case.

PMID- 12236571
TI  - Pulmonary nocardiosis in a non-Hodgkin's lymphoma patient.
AB  - Nocardiosis is an opportunistic infection especially in immunocompromised
      patients. Lungs are the most common infection sites and therapy poses some
      difficulties. We describe a case of pulmonary infection with Nocardia asteroides
      in a non-Hodgkin's lymphoma patient. Although the mortality from pulmonary
      nocardiosis is high in immunocompromised patients, our patient was successfully
      treated with trimethoprim-sulfamethoxazole (TMP/SMZ) and amikacin. Maintenance
      therapy with TMP/SMZ was continued for 1 year. This case supports the importance
      of the long-term maintenance treatment after the initial combination therapy.

PMID- 12236572
TI  - An outbreak of measles in adults living in an enclosed community.

PMID- 12236573
TI  - Transient monoclonal hypergammaglobulinemia during the course of a rickettsia
      infection.

PMID- 12236574
TI  - Native mitral valve endocarditis caused by Staphylococcus lugdunensis in a 22
      year-old woman.

PMID- 12236575
TI  - Ventricular hypertrophy induced by mineralocorticoid treatment or aortic stenosis
      differentially regulates the expression of cardiac K+ channels in the rat.
AB  - Rats treated with DOCA salts and subjected to abdominal aortic stenosis display
      left ventricle hypertrophy associated with a decrease in cardiac I(to) current
      density and prolongation of the action potential duration. We investigated the
      molecular basis of these electrophysiological defects by analyzing the amount of
      mRNA corresponding to the genes encoding the a subunits of the left ventricle K+
      channel at the steady state. The mRNAs corresponding to the a subunits of the K+
      channel (Kv1.2, Kv1.4, Kv1.5, Kv2. 1, Kv4.2 and Kv4.3) were measured by
      quantitative RT-PCR using a specific Kv internal standard. In control rats, the
      Kvl.5 gene was only expressed at a low level, whereas the Kv4.2 and Kv4.3 genes
      were expressed at a high level. Regardless of the etiology of the hypertrophy,
      the amounts of Kv1.4 and Kv1.5 mRNAwere similar in treated, sham and control
      rats. The amounts of Kv1.2 and Kv2.1 mRNA were markedly lower in DOCA-salt
      treated rats (66%) than in sham-DOCA rats, but no effect was observed after
      stenosis. The very conservative Kv4.2 and Kv4.3 genes were found to be
      downregulated simultaneously in both type of hypertrophy. However, the steady
      state amount of Kv4 mRNA was even lower in rats with DOCA-salt-induced
      hypertrophy than in those with stenosis-induced ventricular hypertrophy.
      Therefore, the decrease in I(to) density, consecutively to pressure- and volume
      overload, is due to a large decrease in the amount of Kv4.2 and Kv4.3 mRNA. In
      addition, DOCA-salt treatment alters the amounts of Kv transcripts independently
      to cardiac hypertrophy, suggesting that the mineralocorticoid may be involved in
      Kv gene expression.

PMID- 12236576
TI  - Hematoporphyrin interacts with myoglobin and alters its functions.
AB  - The binding parameters of hematoporphyrin, a photosensitizing drug used in
      photodynamic therapy, interacting with myoglobin, an oxygen storage protein, have
      been studied spectrofluorometrically and spectrophotometrically. Two
      concentration ranges of hematoporphyrin, representing significantly monomeric and
      aggregated (dimeric) states have been used. The binding affinity constant (K)
      decreases and the possible number of binding sites (p) increases as the porphyrin
      changes from significantly monomeric state to predominantly dimeric state.
      Titration of the protein with hematoporphyrin in a spectrophotometric study
      (differential spectroscopy) exhibits an isosbestic point indicating a ground
      state complex formation. The interaction leads to a conformational change of the
      protein as observed in a circular dichroism study. The hematoporphyrin-myoglobin
      interaction causes oxygen release from the protein and it varies with the
      stoichiometric ratio of the porphyrin:protein. Hematoporphyrin also increases the
      myoglobin-catalysed hydrogen peroxide-mediated oxidation of o-dianisidine and
      NADH. These findings on the effects of hematoporphrin-myoglobin interaction
      should be given due consideration in therapeutic uses of the porphyrin and its
      derivatives.

PMID- 12236577
TI  - Estrogen receptor, calcium mobilization and rat sperm motility.
AB  - Oral treatment with 0.4 mg/kg/day of tamoxifen citrate, an antiestrogen, has been
      reported to reduce the fertility of adult male rat, presumably through estrogen
      receptors expressed throughout the male reproductive tract. During the course of
      these studies, tamoxifen was observed to gradually alter the pattern of sperm
      motility in the cauda epididymides without reducing sperm counts. Studies were
      carried out to understand the mechanism involved in tamoxifen induced change in
      the sperm motility pattern. In order to study the direct effects of tamoxifen on
      motility, biochemical levels/activities of sperm calcium, cAMP, phosphodiesterase
      and dynein ATPase, normally implicated in sperm motility were studied In view of
      the fact that tamoxifen is a ligand of estrogen receptor, estrogen receptor alpha
      protein and transcript were localized on rat sperm membrane and the effect of
      tamoxifen studied. The present study demonstrated presence of estrogen receptor
      protein and mRNA in the rat sperm by immunofluorescence, western blotting and in
      situ hybridization respectively. Specificity of sperm estrogen receptors was
      confirmed by conventional binding studies using [3H]-estradiol. There was no
      effect of tamoxifen treatment on estrogen receptors in rat sperms. Biochemical
      analysis of the sperms from tamoxifen treated cauda epididymides revealed a
      significant increase in the levels of calcium and cAMP. A significant reduction
      was also apparent in the activity of dynein ATPase. Tamoxifen treatment did not
      alter phosphodiesterase activity. Estrogen receptors could be identified both in
      the control as well as tamoxifen treated rat sperms. It was concluded that
      tamoxifen treatment mobilized calcium from the intra- or extra-cellular pools
      with a concomitant increase in cAMP and presumably activation of PKA (protein
      kinase A). Tamoxifen altered the pattern of sperm motility through a calcium
      induced block in the activity of dynein ATPase, presumably through the activation
      of sperm phosphatase. The putative estrogen receptor mediated signal transduction
      pathway appears to be directly affected in the tamoxifen treated, sub-motile rat
      sperm.

PMID- 12236578
TI  - An expression of IGF-binding proteins in normal and pre-eclamptic human umbilical
      cord serum and tissues.
AB  - Pre-eclampsia, is the most common, pregnancy-associated pathological syndrome
      accompanied by a significant increase in collagen and sulphated
      glycosaminoglycans (GAGs) contents in the umbilical cord arteries (UCAs). Insulin
      like growth factor-I (IGF-I) is expressed in most foetal tissues and it is
      involved in anabolic effects. It stimulates protein (mainly collagen) and GAG
      biosynthesis, cell proliferation and differentiation. Previously, we have found
      that pre-eclampsia is associated with an increase of IGF-I concentration in the
      umbilical cord blood. A family of IGF-I-binding proteins (BPs) modulates the
      activity of IGF-I. We demonstrated qualitative differences between BPs of normal
      and pre-eclamptic human umbilical cord (UC) serum and UC-tissues (UCA-wall and
      Wharton's jelly) by Western immunoblot analysis. All examined sera and tissues
      contained BP-1 and BP-5 as well lower molecular weight materials. The BP-2 was
      recovered from both control and pre-eclamptic sera, while it was not detected in
      the UC-tissues. Instead, lower molecular weight forms of BP-2 were found as
      judged by the anti-BP-2 antibody. The BP-3 was detected in sera, UCA and
      Wharton's jelly. The most distinct expression of BP-3 was found in the UCA. The
      pre-eclamptic UCA and Wharton's jelly contained additional BP-3-reactive material
      of lower molecular weight. The BP-4 was strongly expressed in pre-eclamptic UC
      serum and the expression was decreased in pre-eclamptic UC-tissues, compared to
      respective controls. Ligand binding assay revealed that most of IGF-I was bound
      to 46 kDa region (typical for BP-3) in both control and pre-eclamptic sera and
      tissues. However, distinctly less IGF-I was bound in pre-eclamptic serum,
      distinctly more in pre-eclamptic UCA and no differences were found in pre
      eclamptic Wharton's jelly, compared to controls. We demonstrated that both normal
      and pre-eclamptic UC-sera and tissues are able to degrade 46 kDa IGF-I-BP. The
      degradation may result in a decrease of IGF-I binding, contributing to increase
      in free IGF-I that may stimulate the cells to produce extracellular matrix (ECM)
      components. The specific BPs and their proteolytic modification in UC tissues may
      be important modulators of IGF-I action during foetal development.

PMID- 12236579
TI  - Purine metabolism and release during cardioprotection with hyperkalemia and
      hypothermia.
AB  - This work investigates whether purine metabolism and release is related to
      cardioprotection with hyperkalemia and hypothermia. Langendorff guinea-pig hearts
      were used to either monitor metabolism during ischemia or to measure functional
      recovery, myocardial injury and release of purine during reperfusion. Hearts
      underwent 30 min ischemia using one of the following protocols: control
      (normothermic buffer), hyperkalaemia (high-potassium buffer), hypothermia (20
      degrees C) and hyperkalemia + hypothermia. At the end of 30 min ischemia,
      hyperkalemia was associated with similar metabolic changes (rise in purine and
      lactate and fall in adenine nucleotides) to control group. Accumulation of purine
      was due to a rise in inosine, xanthine and hypoxanthine and was largely prevented
      by hypothermia and hyperkalemia + hypothermia. Upon reperfusion, there was a time
      dependent release of all purine, lactate and AMP. A fast (peak in less than 20
      sec) release of inosine, xanthine, hypoxanthine and lactate was highest in
      control followed by hyperkalemia then hypothermia and little release in
      hyperkalemia + hypothermia. Adenosine and AMP release was slow (peak at 3 min),
      only significant in control and was likely to be due to sarcolemmal disruption as
      the profile followed lactate dehydrogenase release. Recovery (left ventricular
      developed pressure) was 63% control, 82% hyperkalemia, 77% hypothermia and 98%
      for hyperkalemia + hypothermia. The loss of purine during reperfusion but not
      their production during ischemia is related to cardioprotection with
      hyperkalemia. The possibility that the consequences of hyperkalemia modulate a
      sodium-dependent purine efflux, is discussed. The reduced loss of purine in
      hypothermia or in hyperkalemia + hypothermia is likely to be due to a lower
      metabolic activity during ischemia.

PMID- 12236580
TI  - Antihypertensive and metabolic effects of whole Maitake mushroom powder and its
      fractions in two rat strains.
AB  - Maitake mushroom has been reported to favorably influence hypertension and
      diabetes mellitus. The purpose of this study was to compare the effects of whole
      Maitake mushroom powder and two extracts designated as ether soluble (ES) and
      water soluble (WS) on Zucker fatty rats (ZFR), a model of insulin resistance, and
      on spontaneously hypertensive rats (SHR), a model of genetic hypertension. In the
      initial study, we followed four groups of eight ZFR and SHR receiving special
      diets: a baseline diet (BD), BD + whole Maitake mushroom powder (20% w/w), BD +
      fraction ES (0.10% w/w), and BD + WS (0.22% w/w). Different effects of these
      dietary regimens on the 2 rat strains were found. At 35 days, only consumption of
      the ES diet significantly decreased systolic BP (SBP) in SHR (average 197 vs. 176
      mm Hg, p < 0.001), while in ZFR only the groups consuming the whole Maitake and
      WS diets showed significantly decreased SBP (138 vs. 120-125 mm Hg, p < 0.001). A
      challenge test with losartan (an angiotensin II receptor blocker) indicates that
      angiotensin II does not play a major role in SBP regulation of ZFR, but does in
      SHR where consumption of ES relative to other groups significantly lowered
      activity of this system. In SHR, glucose, cholesterol, circulating insulin and
      HbA1C were virtually similar among all dietary groups; but whole Maitake (-22%),
      ES (-120%) and WS (-80%) diets were associated with decreased triglycerides, and
      the ES diet with lowered serum creatinine (-29%). In ZFR, circulating insulin and
      HbA1C were significantly decreased in the whole Maitake powder and ES groups, and
      tended to be lower in the WS group compared to control. In the ensuing studies,
      we gavaged ZFR once daily with water (control), 44 mg fraction WS, or 44 mg
      fraction WS plus 100 microg niacin-bound chromium (NBC). Oral gavage of WS
      clearly lowered SBP and circulating glucose concentrations, more so with the
      addition of chromium. We conclude that the examined forms of Maitake mushroom
      have antihypertensive and antidiabetic potential which differ among rat strains.
      The ES fraction may decrease SBP in SHR via alteration in the renin-angiotensin
      system.

PMID- 12236581
TI  - Inhibition of HTLV-1 transcription by cyclin dependent kinase inhibitors.
AB  - HTLV-1 is the etiologic agent for adult T-cell leukemia/lymphoma (ATL) and HTLV-1
      associated myelopathy/tropical spastic paraparesis (HAM/TSP), where viral
      replication and transformation are largely dependent upon modification of
      regulatory and host cell cycle proteins. The mechanism of HTLV-1 transformation
      appears to be distinct from that of many known chronic or acute leukemia viruses
      and is related to the viral activator Tax. Here we show that cyclin E, can
      associate tightly with the coactivator p300 and Pol II complex in HTLV-1 infected
      cells. The cyclin E associated complex is kinase active and phosphorylates the
      carboxy terminal domain of RNA Pol II. More importantly, p21/Waf1, a well-known
      cdk inhibitor at the G1/S border, inhibits transcription of HTLV-1 in both
      transfections and in in vitro transcription assays. Finally, specific cdk
      chemical inhibitors, functionally similar to cellular cdkIs, such as p21/Waf1
      which inhibits cyclin E/cdk2 activity, also inhibit transcription of the HTLV-1
      promoter. In particular, Purvalanol A, with an IC50 of 0.035 microm inhibits
      activated, but not basal transcription, as well as HTLV-1 infected cells.
      Collectively, the role of cyclin E/cdk2 in HTLV-1 infected cells and its
      involvement in RNA Pol II phosphorylation is discussed.

PMID- 12236582
TI  - ATP binding cassette transporter A1--key roles in cellular lipid transport and
      atherosclerosis.
AB  - ATP-binding cassette transporter A1 (ABCA1) was recently recognized as the mutant
      molecule responsible for Tangier disease with low HDL levels, accumulation of
      cholesteryl esters in tissues, and increased risk of cardiovascular disease.
      Extensive studies for the past 2 years have recognized the critical role of ABCA1
      in cholesterol and phospholipid trafficking. Since the removal of cholesterol
      from tissues is a key step in the prevention of atherosclerosis, significant
      attention has been focused on this molecule. Natural ABCA1 mutations in Tangier
      disease (TD) patients and WHAM chickens together with induced mutation in ABCA1
      knock-out mice unequivocally established the important role of ABCA1 in
      maintaining circulating HDL levels and promoting cholesterol efflux from the
      arterial wall. Mice lacking ABCA1 showed similar phenotypes observed in Tangier
      disease patients with low levels of HDL. Further understanding of the roles of
      ABCA1 in lipid transport and atherosclerosis became clear from studies with ABCA1
      transgenic mice. These mice showed enhanced cholesterol efflux from macrophages
      and reduced atherosclerotic lesion formation. The promoter of the ABCA1 gene has
      been mapped to a large extent, with the exception of cAMP response element. The
      present review summarizes recent developments on the role of ABCA1 in cholesterol
      efflux and prevention of atherosclerosis. Given the antiatherogenic properties of
      ABCA1, this molecule can serve as an appropriate target for developing drugs to
      treat individuals with low levels of HDL.

PMID- 12236583
TI  - Probing the role of active site histidine residues in the catalytic activity of
      lacrimal gland peroxidase.
AB  - The role of active site histidine residues in SCN- oxidation by lacrimal gland
      peroxidase (LGP) has been probed after modification with diethylpyrocarbonate
      (DEPC). The enzyme is irreversibly inactivated following pseudo-first order
      kinetics with a second order rate constant of 0.26 M(-1) sec(-1) at 25 degrees C.
      The pH dependent rate of inactivation shows an inflection point at 6.6 indicating
      histidine derivatization. The UV difference spectrum of the modified vs. native
      enzyme shows a peak at 242 nm indicating formation of N-carbethoxyhistidine.
      Carbethoxyhistidine formation and associated inactivation are reversed by
      hydroxylamine indicating histidine modification. The stoichiometry of histidine
      modification and the extent of inactivation show that out of five histidine
      residues modified, modification of two residues inactivates the enzyme. Substrate
      protection with SCN- during modification indicates that although one histidine is
      protected, it does not prevent inactivation. The spectroscopically detectable
      compound II formation is lost due to modification and is not evident after SCN-
      protection. The data indicate that out of two histidines, one regulates compound
      I formation while the other one controls SCN- binding. SCN- protected enzyme is
      inactive due to loss of compound I formation. SCN- binding studies by optical
      difference spectroscopy indicate that while the native enzyme binds SCN- with the
      Kd of 15 mM, the modified enzyme shows very weak binding with the Kd of 660 mM.
      From the pH dependent binding of SCN-, a plot of log Kd vs. pH shows a sigmoidal
      curve from which the involvement of an enzyme ionizable group of pKa 6.6 is
      ascertained and attributed to the histidine residue controlling SCN- binding. LGP
      has thus two distinctly different essential histidine residues - one regulates
      compound I formation while the other one controls SCN- binding.

PMID- 12236584
TI  - Dexamethasone induces the secretion of annexin I in immature lymphoblastic cells
      by a calcium-dependent mechanism.
AB  - The mechanisms by which glucocorticoids (GC) regulate annexin I (ANXA1) secretion
      in different cells are still a matter of debate. The aims of this study were to
      evaluate the ability of dexamethasone (Dex) to induce ANXA1 secretion and to
      investigate the roles of the intracellular free Ca2+ concentration ([Ca2+]i), and
      of the GC receptor, on that process. For this purpose, the human immature
      lymphoblastic CCRF-CEM cell line was used. Treatment of the cells with Dex, for
      up to 4 h, significantly reduced the intracellular content of ANXA1 and increased
      the amount of this protein bound to the outer surface of the plasma membrane,
      whereas exposure of cells to Dex, for 12 h, induced the synthesis of ANXA1. At
      the same short time periods, Dex also induced a significant increase in the
      [Ca2+]i. Incubation of the cells with BAPTA-AM (10 microM), a cell-permeant high
      affinity Ca2+ chelator, completely inhibited Dex-induced ANXA1 secretion.
      Furthermore, the Ca2+ ionophore, ionomycin, alone induced ANXA1 cleavage, but not
      its secretion. Additionally, we used brefeldin A to investigate the involvement
      of the classical endoplasmic reticulum (ER)-Golgi pathway of protein secretion in
      the release of ANXA1. The GC receptor antagonist, RU486, neither reverted the Dex
      dependent ANXA1 secretion nor inhibited the increase of the [Ca2+]i induced by
      Dex. Together, our results indicate that Dex induces ANXA1 synthesis and
      secretion in CCRF-CEM cells. ANXA1 secretion in this cell type show the following
      characteristics: (i) is unlikely to involve the classical ER-Golgi pathway; (ii)
      requires a Ca(2+)-dependent cleavage of ANXA1; (iii) involves both Ca(2+)
      dependent and independent mechanisms; and (iv) is apparently independent of the
      GC receptor alpha isoform.

PMID- 12236585
TI  - Post-translational modifications of cardiac tubulin during chronic heart failure
      in the rat.
AB  - Cytoskeletal reorganization has been shown to participate in cellular remodeling
      and in the alterations of mechanical function of isolated cardiomyocytes during
      pressure overload hypertrophy. Post-translational modifications of tubulin
      towards stabilization of microtubules have also been described in animal models
      of compensatory hypertrophy, but the status of the microtubules network in end
      stage heart failure is not clearly established. Using a rat model of congestive
      heart failure (CHF) induced by aortic banding, we studied the expression of alpha
      and beta-tubulin, as well as their post-translational modification and
      distribution in the soluble and polymerized fraction by immunoblotting. We found
      an accumulation of alpha- and beta-tubulin protein content specifically in the
      soluble fraction with no change in the polymerized fraction. Amongst the several
      variants of alpha-tubulin examined, only detyrosinated Glu-tubulin and
      deglutamylated delta2-tubulin levels were selectively increased during heart
      failure. Glu-tubulin accumulated in the polymerized fraction while delta2-tubulin
      levels were increased in the soluble fraction in CHF hearts. These results show
      that a profound remodeling of the microtubule network occurs in heart failure.
      This remodeling suggests an increase in the stability of the microtubule network
      which is discussed in terms of possible functional consequences.

PMID- 12236586
TI  - In vitro lead-induced cell toxicity and cytoprotective activity of fetal calf
      serum in human fibroblasts.
AB  - The underlying mechanisms by which lead ions produce their deleterious effects
      prior to the onset of clinical symptoms are incompletely understood. This study
      aimed to assess lead-induced cell toxicity mechanisms by focusing on the effects
      of the metal on cell growth, DNA synthesis, cellular ATP, intracellular
      hexosaminidase activity and lysosomal function, and examine the possible
      cytoprotective role of fetal calf serum (FCS). Several human dermal cultured
      fibroblast lines were exposed to Pb (400 microM) for 1-6 days with 2, 5, and 10%
      FCS. The earliest toxic effect of Pb was significant inhibition of DNA synthesis
      after 24 h direct exposure; this harmful effect was not progressive during the
      first 3 days, but worsened clearly on the 4th day regardless of the FCS
      concentration. Atime-dependent depletion of intracellularATP content was also
      caused by ionic lead, thereby compromising the cell energy charge which precedes
      cell death. Fibroblast growth was progressively and significantly inhibited from
      day 2 onwards; the greatest noxious effect was observed in the presence of 2%
      FCS: 49% reduction in cell proliferation after 5 days. Lead salts produced loss
      of cell adhesion to the culture dish which worsened from the 2nd day and was more
      pronounced when FCS in growth medium was decreased. Toxic actions on lysosomal
      membrane integrity provoked a decrease in neutral red uptake (NRU) which was
      exposure time-dependent and more marked with 2% FCS. In contrast, increased
      relative NRU (to 20% at 4 days), suggestive of endocytosis-induced lysosome
      enlargement, was observed in Pb-exposed cells. Intracellular hexosaminidase
      activity was not negatively affected until 5 days after exposure to Pb salts. FCS
      had a significant cytoprotective effect on Pb-induced toxicity.

PMID- 12236587
TI  - Cytoplasmic-nuclear shuttling of the urokinase mRNA binding protein regulates
      message stability.
AB  - Treatment of small airway epithelial (SAEC) cells or lung epithelial (Beas2B)
      cells with TNF-alpha or PMA induces urokinase-type plasminogen activator (uPA)
      expression. Treatment of these cells with TNF-alpha, PMA or cycloheximide but not
      TGF-beta increased steady-state expression of uPAmRNA. TNF-alpha, PMA or
      cycloheximide caused 8-10 fold extensions of the uPAmRNA half-life in SAEC or
      Beas2B cells treated with DRB, a transcriptional inhibitor. These findings
      suggest that uPA gene expression involves a post-transcriptional regulatory
      mechanism. Using gel mobility shift and UV cross-linking assays, we identified a
      30 kDa uPA mRNA binding protein (uPA mRNABp) that selectively binds to a 66 nt
      protein binding fragment of uPA mRNA containing regulatory information for
      message stabilization. Binding of cytoplasmic uPA mRNABp to uPA mRNA was
      abolished after treatment with TNF-alpha but not TGF-beta. In addition, we found
      the accumulation of 30 kDa uPAmRNABp in the nuclear extracts of TNF-alpha but not
      TGF-beta treated cells. The uPA mRNABp starts moving to the nucleus from the
      cytoplasmic compartment as early as three hours after TNF-alpha treatment.
      Complete translocation is achieved between 12-24 h, which coincides with the
      maximal expression of uPA protein effected by cytokine stimulation. Treatment of
      Beas2B cells with NaF inhibited TNF-alpha-mediated translocation of uPA mRNABp
      from the cytoplasm to the nucleus and concomitant inhibition of uPA expression.
      TNF-alpha stabilizes uPA mRNA by translocating the uPA mRNABp from the cytoplasm
      to the nucleus. Our results demonstrate a novel mechanism governing uPA mRNA
      stability through shuttling of uPA mRNABp between the nucleus and cytoplasm. This
      newly identified pathway may have evolved to regulate uPA-mediated functions of
      the lung epithelium in inflamation or neoplasia.

PMID- 12236588
TI  - Effect of N1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase,
      on endothelial cell growth, differentiation and apoptosis.
AB  - An unusual amino acid, hypusine [Nepsilon-(4-amino-2-hydroxybutyl)lysine], is
      formed post-translationally in a single cellular protein, the eukaryotic
      translation initiation factor 5A (eIF5A) by deoxyhypusine synthase and
      deoxyhypusine hydroxylase. Although eIF5A and its hypusine modification are
      essential for eukaryotic cell viability, the true physiological function of eIF5A
      is yet unknown. We have examined the effects of N1-guanyl-1,7-diaminoheptane
      (GC7), a potent inhibitor of deoxyhypusine synthase, on endothelial cell
      proliferation, differentiation and apoptosis. Upon treatment of human umbilical
      vein endothelial cells (HUVEC) with GC7, dose-dependent inhibition of hypusine
      formation and cellular proliferation was observed. GC7 at 10 microM caused almost
      complete inhibition of cellular hypusine synthesis and led to cytostasis of
      HUVEC. Pretreatment of HUVEC with GC7 up to 50 microM for 4 days had little
      effect on the attachment and differentiation of these cells on Matri-gel and did
      not cause induction of apoptosis. Instead, the GC7 pretreatment (96 h at 5-50
      microM) elicited protective effects against apoptotic death of HUVEC induced by
      serum starvation. These results suggest that eIF-5A may be involved in expression
      of proteins essential for apoptosis of endothelial cells as well as those for
      cellular proliferation.

PMID- 12236589
TI  - Dietary vitamin C supplementation decreases blood pressure in DOCA-salt
      hypertensive male Sprague-Dawley rats and this is associated with increased liver
      oxidative stress.
AB  - The effects of a vitamin C supplemented diet on blood pressure, body and liver
      weights, liver antioxidant status, iron and copper levels were investigated in
      DOCA-salt treated and untreated Sprague-Dawley (SD) male rats after 8 weeks of
      treatment. Vitamin C supplementation had no effect on blood pressure in SD rats
      but induced a significant decrease in blood pressure in DOCA-salt treated rats,
      the decrease being more efficient at 50 mg/kg of vitamin C than at 500 mg/kg.
      Hepatic lipid peroxidation and iron levels were significantly increased in DOCA
      salt hypertensive rats whereas total hepatic antioxidant capacity (HAC),
      glutathione peroxidase (GSH-Px) and catalase (CAT) activities were decreased.
      Vitamin C supplementation did not affect the overall antioxidant defences of
      control SD rat livers. In contrast, vitamin C supplementation accentuated the
      DOCA-salt induced accumulation of liver iron and lipid peroxidation. This
      occurred without any notable aggravation in the antioxidant deficiency of vitamin
      C supplemented DOCA-salt treated rat livers. Our data suggest that DOCA-salt
      treatment induces an accumulation of iron in rat livers which is responsible for
      the prooxidant effect of vitamin C. The normalization of blood pressure in DOCA
      salt treated rats by vitamin C supplementation appears thus independent from
      liver antioxidant status.

PMID- 12236590
TI  - Role of membrane-associated Ca+ dependent matrix metalloprotease-2 in the oxidant
      activation of Ca2+Atpase by tertiary butylhydroperoxide.
AB  - Treatment of bovine pulmonary artery smooth muscle plasma membrane suspension
      with the oxidant tert-butylhydroperoxide (t-buOOH) increases Ca2+ATPase activity.
      The smooth muscle plasma membrane possesses a Ca2+ dependent protease activity in
      the gelatin containing zymogram having an apparent molecular mass of 72 kDa. The
      72 kDa protease activity was found to be inhibited by EGTA and the tissue
      inhibitor of metalloprotease-2 (TIMP-2). Since 72 kDa is the molecular mass of
      MMP-2 and since in our present study the 72 kDa protease in the gelatin
      containing zymogram is inhibited by matrix metalloprotease inhibitors, EGTA and
      TIMP-2, it may be suggested that the 72 kDa protease is the MMP-2. In addition to
      the increasing Ca2+ATPase activity, t-buOOH also enhances the activity of the
      membrane associated Ca2+ dependent protease that degrades 14C-gelatin. The
      oxidant triggered protease activity and the Ca2+ATPase activity were found to be
      prevented by the antioxidant vitamin E, and also by the Ca2+ dependent matrix
      metalloprotease inhibitors: EGTA and TIMP-2. Adding MMP-2 to the smooth muscle
      plasma membrane suspension caused an increase in Ca2+ATPase activity and
      pretreatment with TIMP-2 prevents the increase in Ca2+ATPase activity. Combined
      treatment of the smooth muscle plasma membrane with low doses of MMP-2 and t
      buOOH augments further the Ca2+ATPase activity caused by the respective doses of
      either t-buOOH or MMP-2. Pretreatment with TIMP-2 prevents the increase in
      Ca2+ATPase activity elicited by the low doses of MMP-2 and/or t-buOOH.

PMID- 12236591
TI  - Purification and characterization of a potent hemolytic toxin with phospholipase
      A2 activity from the venom of Indian Russell's viper.
AB  - A potent toxin with phospholipase A2 (PLA2) and hemolytic activity in vitro was
      purified from the Russell's viper venom of eastern India (RVV-EI). The purified
      protein (RVV-PFIIc') of 15.3 kDa molecular weight, and a lethal toxicity dose
      (LD50i.p.) of 0.1 mg/kg body weight, was the most toxic PLA2 so far reported from
      the Indian subcontinent. The material also possessed anticoagulant activity as it
      enhanced the prothrombin induced plasma clotting time in vitro. The PLA2 toxin
      (RVV-PFIIc') was shown to be different from other PLA2s of RVV in respect to one
      or more of these parameters e.g. molecular weight, isoelectric pH, in vivo
      toxicity, specific activity of the enzyme and certain other biological
      activities. The first 19 amino terminal sequence (NLFQFAEMIVKMTGKEAVH) of RVV
      PFIIc' showed variable degree of homology (42.1-94.7%) with those of other RVV
      PLA2s described in the literature. Antisera raised against RVV-EI or RVV-PFIIc',
      though completely neutralized the in vivo lethal toxicity of RVV-EI or RVV
      PFIIc', failed to inhibit their PLA2 activity in vitro thereby suggesting that in
      vivo toxicity and in vitro activity of the enzyme may not be directly related.
      Apart from RVV-PFIIc', at least two other PLA2 isozymes were found to be present
      in RVV-EI that were distinct from RVV-PFIIc' in respect to their molecular,
      biological as well as serological properties. The significance of these and
      related data in antivenom therapy is discussed.

PMID- 12236592
TI  - Rapid colorimetric quantification of lipo-chitooligosaccharides from
      Mesorhizobium loti and Sinorhizobium meliloti.
AB  - Nod factors are lipids with a chitinlike headgroup produced by gram-negative
      Rhizobium bacteria. These lipo-chitooligosaccharides (LCOs) are essential
      signaling molecules for accomplishing symbiosis between the bacteria and roots of
      legume plants. Despite their important role in the Rhizobium-legume interaction,
      no fast and sensitive Nod factor quantification methods exist. Here, we report
      two different quantification methods. The first is based on the enzymatic
      hydrolysis of Nod factors to release N-acetylglucosamine (GlcNAc), which can
      subsequently be quantified. It is shown that the degrading enzyme, glusulase,
      releases exactly two GlcNAc units per pentameric nodulation factor from
      Mesorhizobium loti factor, allowing quantification of LCOs from Mesorhizobium
      loti. The second method is based on a specific type of Nod factors that are
      sulfated on the reducing GlcNAc, allowing quantification analogous to the
      quantification of sulfolipids. Here, a two-phase extraction method is used in the
      presence of methylene blue, which specifically forms an ion pair with sulfated
      lipids. The blue ion pair partitions into the organic phase, after which the
      methylene blue signal can be quantified. To enable Nod factor quantification with
      this method, the organic phase was modified and the partitioning was evaluated
      using fluorescent and radiolabeled sulfated Nod factors. It is shown that
      sulfated LCOs can be quantified with this method, using sodium dodecyl sulfate
      for calibration. Both methods allow Nod factor quantification in parallel
      enabling a fast and easy detection of nanomole quantities of Nod factors.
      Accurate Nod factor quantification will be crucial for characterization and cross
      comparison of the affinity for Nod factors of newly identified Nod factor binding
      proteins or putative Nod factor receptors.

PMID- 12236593
TI  - Engineering bacterial competitiveness and persistence in the phytosphere.
AB  - Several tactics exist to improve the survival of an introduced microorganism of
      interest in the plant environment. One, derived from studies on the Agrobacterium
      plant interaction and the role of opines in this interaction, proposes to promote
      growth of the inoculant in the plant environment via the establishment of a bias
      in the rhizosphere. It is supported by the occurrence of natural biases, such as
      those generated by opine-like molecules, by calestegins, or by mimosine. Opine
      mediated biases have allowed several investigators to favor the growth of opine
      degrading bacteria or communities under sterile or axenic environments or in
      microcosms mimicking near field conditions. Another way to favor a given microbe
      consists in impeding growth of competing microorganisms. Experiments performed
      using detergent or bacteriostatic agents as amendments under field or near field
      conditions yielded promising results. Research perspectives for engineering plant
      microbe interactions also include specific engineering of predation and
      strategies designed to interfere with some of the signals perceived by the
      microbes, provided these signals control the expression of functions central to
      microbial fitness. In this respect, quorum-sensing signal molecules, such as N
      acyl-homoserine lactones, may be valuable targets for the development of
      biocontrol agents and procedures.

PMID- 12236594
TI  - Synergistic effect of deoxyanthocyanins from symbiotic fern Azolla spp. on hrmA
      gene induction in the cyanobacterium Nostoc punctiforme.
AB  - The hrmA gene of the N2-fixing cyanobacterium Nostoc punctiforme functions in
      repressing the formation of transitory motile filaments, termed hormogonia, by
      plant-associated vegetative filaments. Here, we report that anthocyanins can
      contribute to induction of hrmA expression. Aqueous extract from fronds of the
      fern Azolla pinnata, a host of symbiotic Nostoc spp., was found to be a potent
      inducer of hrmA-luxAB in N. punctiforme strain UCD 328. The hrmA-luxAB inducing
      activities of A. pinnata, as well as Azolla filiculoides, were positively
      correlated with levels of frond deoxyanthocyanins. Analyses of the
      deoxyanthocyanins in frond extracts revealed, in order of predominance, an
      acetylated glycoside derivative of luteolinidin (m/z 475) and of apigeninidin
      (m/z 459) and minor amounts of a second luteolinidin derivative. At up to 150
      microM, a purified preparation of deoxyanthocyanins only weakly induced hrmA
      luxAB on its own, but mixtures with hrmA-luxAB inducers (A. filiculoides extract
      or the flavonoid naringin) synergistically doubled to tripled their inducing
      activities. These results suggest that appropriately localized deoxyanthocyanins
      could function in plant-mediated mechanisms for repressing Nostoc spp.
      hormogonium formation.

PMID- 12236595
TI  - A decarboxylase encoded at the Cochliobolus heterostrophus translocation
      associated Tox1B locus is required for polyketide (T-toxin) biosynthesis and high
      virulence on T-cytoplasm maize.
AB  - Genes at two unlinked loci (Tox1A and Tox1B) are required for production of the
      polyketide T-toxin by Cochliobolus heterostrophus race T, a pathogenic fungus
      that requires T-toxin for high virulence to maize with T-cytoplasm. Previous work
      indicated that Tox1A encodes a polyketide synthase (PKS1) required for T-toxin
      biosynthesis and for high virulence. To identify genes at Tox1B, a wild-type race
      T cDNA library was screened for genes missing in the genome of a Tox1B deletion
      mutant. The library was probed, first with a 415-kb NotI restriction fragment
      from the genome of the Tox1B mutant, then with the corresponding 560-kb fragment
      from the genome of wild type. Two genes, DEC1 (similar to acetoacetate
      decarboxylase-encoding genes) and RED1 (similar to genes encoding members of the
      medium-chain dehydrogenase/reductase superfamily), were recovered. Targeted
      disruption of DEC1 drastically reduced both T-toxin production and virulence of
      race T to T-cytoplasm maize, whereas specific inactivation of RED1 had no
      apparent effect on T-toxin production (as determined by bioassay) or on
      virulence. DEC1 and RED1 map within 1.5 kb of each other on Tox1B chromosome 6;12
      and are unique to the genome of race T, an observation consistent with the
      hypothesis that these genes were acquired by C. heterostrophus via a horizontal
      transfer event.

PMID- 12236596
TI  - Infection and colonization of rice seedlings by the plant growth-promoting
      bacterium Herbaspirillum seropedicae Z67.
AB  - A beta-glucoronidase (GUS)-marked strain of Herbaspirillum seropedicae Z67 was
      inoculated onto rice seedling cvs. IR42 and IR72. Internal populations peaked at
      over 10(6) log CFU per gram of fresh weight by 5 to 7 days after inoculation
      (DAI) but declined to 10(3) to 10(4) log CFU per gram of fresh weight by 28 DAI.
      GUS staining was most intense on coleoptiles, lateral roots, and at the junctions
      of some of the main and lateral roots. Bacteria entered the roots via cracks at
      the points of lateral root emergence, with cv. IR72 appearing to be more
      aggressively infected than cv. IR42. H. seropedicae subsequently colonized the
      root intercellular spaces, aerenchyma, and cortical cells, with a few penetrating
      the stele to enter the vascular tissue. Xylem vessels in leaves and stems were
      extensively colonized at 2 DAI but, in later harvests (7 and 13 DAI), a host
      defense reaction was often observed. Dense colonies of H. seropedicae with some
      bacteria expressing nitrogenase Fe-protein were seen within leaf and stem
      epidermal cells, intercellular spaces, and substomatal cavities up until 28 DAI.
      Epiphytic bacteria were also seen. Both varieties showed nitrogenase activity but
      only with added C, and the dry weights of the inoculated plants were
      significantly increased. Only cv. IR42 showed a significant (approximately 30%)
      increase in N content above that of the uninoculated controls, and it also
      incorporated a significant amount of 15N2.

PMID- 12236597
TI  - Characterization and evolutionary analysis of a large polygalacturonase gene
      family in the oomycete plant pathogen Phytophthora cinnamomi.
AB  - Polygalacturonases (PGs) are secreted by fungal pathogens during saprophytic and
      parasitic growth, and their degradation of pectin in the plant cell wall is
      believed to play a major role in tissue invasion and maceration. In this study,
      PG activity was demonstrated in culture filtrates of the oomycete plant pathogen,
      Phytophthora cinnamomi. A P. cinnamomi pg gene fragment amplified using
      degenerate primers based on conserved regions in fungal and plant PGs was used to
      isolate 17 complete P. cinnamomi pg genes and pseudogenes from a genomic library
      and partial sequence for another two genes. Gel blotting of genomic DNA indicated
      that there may be even more pg genes in the P. cinnamomi genome. P. cinnamomi pg
      gene sequences were expressed in PG-deficient yeast and found to confer PG
      activity, thereby confirming their functional identity. The predicted mature P.
      cinnamomi PGs fall into subgroups that exhibit large differences in the extent of
      N-glycosylation, isoelectric points, and N- and C-terminal structure. Evidence
      for birth-and-death and reticulate evolution in the P. cinnamomi pg gene family
      was obtained, and some codons for surface exposed residues in the P. cinnamomi
      PGs were shown to have been subject to diversifying selection. Contrary to
      accepted phylogenies for other proteins, phylogenetic analysis of the P.
      cinnamomi PGs revealed a closer relationship with PGs from true fungi than with
      those from plants.

PMID- 12236598
TI  - Glycine-rich proteins encoded by a nodule-specific gene family are implicated in
      different stages of symbiotic nodule development in Medicago spp.
AB  - Four genes encoding small proteins with significantly high glycine content have
      been identified from root nodules of Medicago sativa. All of these proteins as
      well as their Medicago truncatula homologues carried an amino terminal signal
      peptide and a glycine-rich carboxy terminal domain. All except nodGRP3 lacked the
      characteristic repeat structure described for cell wall and stress response
      related glycine-rich proteins (GRP). Expression of these GRP genes was
      undetectable in flower, leaf, stem, and hypocotyl cells, whereas expression was
      highly induced during root nodule development, suggesting that GRP genes act as
      nodulins. Moreover, none of these nodule-expressed GRP genes were activated by
      hormones or stress treatments, which are inducers of many other GRPs. In
      Rhizobium-free spontaneous nodules and in nodules induced by a noninfective
      mutant strain of Sinorhizobium meliloti, all these genes were repressed, while
      they were induced in Fix- nodules, unaffected in bacterial infection, but halted
      in bacteroid differentiation. These results demonstrated that bacterial infection
      but not bacteroid differentiation is required for the induction of the nodule
      specific GRP genes. Differences in kinetics and localization of gene activation
      as well as in the primary structure of proteins suggest nonredundant roles for
      these GRPs in nodule organogenesis.

PMID- 12236599
TI  - The indolic compound hypaphorine produced by ectomycorrhizal fungus interferes
      with auxin action and evokes early responses in nonhost Arabidopsis thaliana.
AB  - Signals leading to mycorrhizal differentiation are largely unknown. We have
      studied the sensitivity of the root system from plant model Arabidopsis thaliana
      to hypaphorine, the major indolic compound isolated from the basidiomycetous
      fungus Pisolithus tinctorius. This fungi establishes ectomycorrhizas with
      Eucalyptus globulus. Hypaphorine controls root hair elongation and counteracts
      the activity of indole-3-acetic acid on root elongation on A. thaliana, as
      previously reported for the host plant. In addition, we show that hypaphorine
      counteracts the rapid upregulation by indole-3-acetic acid and 1-naphthalenic
      acetic acid of the primary auxin-responsive gene IAA1 and induces a rapid,
      transient membrane depolarization in root hairs and suspension cells, due to the
      modulation of anion and K+ currents. These early responses indicate that
      components necessary for symbiosis-related differentiation events are present in
      the nonhost plant A. thaliana and provide tools for the dissection of the
      hypaphorine-auxin interaction.

PMID- 12236600
TI  - Phospholipase D in Phytophthora infestans and its role in zoospore encystment.
AB  - We show that differentiation of zoospores of the late blight pathogen
      Phytophthora infestans into cysts, a process called encystment, was triggered by
      both phosphatidic acid (PA) and the G-protein activator mastoparan. Mastoparan
      induced the accumulation of PA, indicating that encystment by mastoparan most
      likely acts through PA. Likewise, mechanical agitation of zoospores, which often
      is used to induce synchronized encystment, resulted in increased levels of PA.
      The levels of diacylglycerolpyrophosphate (DGPP), the phosphorylation product of
      PA, increased simultaneously. Also in cysts, sporangiospores, and mycelium,
      mastoparan induced increases in the levels of PA and DGPP. Using an in vivo assay
      for phospholipase D (PLD) activity, it was shown that the mastoparan-induced
      increase in PA was due to a stimulation of the activity of this enzyme.
      Phospholipase C in combination with diacylglycerol (DAG) kinase activity also can
      generate PA, but activation of these enzymes by mastoparan was not detected under
      conditions selected to highlight 32P-PA production via DAG kinase. Primary and
      secondary butanol, which, like mastoparan, have been reported to activate G
      proteins, also stimulated PLD activity, whereas the inactive tertiary isomer did
      not. Similarly, encystment was induced by n- and sec-butanol but not by tert
      butanol. Together, these results show that Phytophthora infestans contains a
      mastoparan- and butanol-inducible PLD pathway and strongly indicate that PLD is
      involved in zoospore encystment. The role of G-proteins in this process is
      discussed.

PMID- 12236601
TI  - Differential virulence by strains of Cucumber mosaic virus is mediated by the 2b
      gene.
AB  - The approximately 12-kDa 2b protein, encoded by all cucumoviruses, had been shown
      to play an important role in viral long-distance movement, hypervirulence, and
      suppression of post-transcriptional gene silencing. The role of the 2b gene in
      the hypervirulence of Cucumber mosaic virus (CMV) and whether hypervirulence was
      linked to movement were analyzed using a hybrid virus (CMV-qw), generated by
      replacing the 2b gene in a subgroup II strain, Q-CMV, with the 2b gene from a
      subgroup IA strain, WAII-CMV. CMV-qw was more virulent than Q-CMV or WAII-CMV on
      most of the host plant species tested. Northern blot and nucleotide sequence
      analyses demonstrated that CMV-qw was stably maintained during the course of
      infection and upon passage. Kinetic studies revealed that the hypervirulence
      induced by the hybrid virus was associated with neither increased viral RNA
      accumulation nor more rapid viral movement per se, suggesting that other
      functions of the 2b protein are important in determining the hypervirulence.

PMID- 12236602
TI  - The rolB-like part of the Agrobacterium rhizogenes orf8 gene inhibits sucrose
      export in tobacco.
AB  - Many Agrobacterium T-DNA genes belong to the highly diverse rolB family. The mode
      of action of most of these genes is still unknown. rolB-like sequences also are
      present at the 5' ends of the T-DNA-located iaaM genes and the iaaM homolog orf8,
      whereas iaaM genes from Pseudomonas and Erwinia spp. lack such sequences. iaaM
      genes encode tryptophan monooxygenases; these enzymes convert tryptophan into
      indole-3-acetamide, a precursor of indole-3-acetic acid. Tobacco plants
      expressing the rolB-like part of the A4 orf8 gene (2x35S-A4-Norf8 plants)
      accumulate glucose, fructose, sucrose, and starch and resemble sucrose
      transporter (NtSUT1) antisense plants. Different lines of evidence indicate that
      2x35S-A4-Norf8 plants export less sucrose from source leaves. Glucose, fructose,
      sucrose, and starch accumulate in source leaves during sink-source transition,
      whereas sink tissues like petioles and midveins contain lower levels than normal.
      Petiole exudation experiments demonstrate a significant decrease in export of
      label after 14C-sucrose infiltration and after 14CO2 labeling. Grafting of
      stunted homozygous 2x35S-A4-Norf8 plants onto wild-type rootstocks restores
      growth, indicating that unloading is not affected. Growth of 2x35S-A4-Norf8
      seedlings is inhibited on naphthalene acetic acid-containing media, suggesting a
      link between sucrose transport and auxin sensitivity.

PMID- 12236603
TI  - Characterization of early, chitin-induced gene expression in Arabidopsis.
AB  - Three genes (i.e., a zinc finger protein, a lectin-like protein, and AtMPK3),
      previously shown to respond to chitin elicitation in microarray experiments, were
      used to examine the response of Arabidopsis spp. to chitin addition. Maximum
      induction for all three genes was found upon addition of crab-shell chitin at 100
      mg per liter. Threefold induction was found with a chitin concentration as low as
      10(-4) mg per liter. The specificity of this response was examined using purified
      chitin oligomers (degree of polymerization = 2 to 8). The larger chitin oligomers
      (hexamer to octamer), were most effective in inducing expression of the three
      genes assayed. Gene induction was observed after the addition of 1 nM chitin
      octamer. The protein kinase inhibitors staurosporine and K252a effectively
      suppressed chitin-induced gene expression, while the protein phosphatase
      inhibitors calyculin A and okadaic acid induced the accumulation of mRNA in the
      absence of chitin. The phosphorylation event necessary for transmission of the
      chitin signal was completed within the first 20 min of chitin addition. The level
      of chitin-induced gene expression of the lectin-like protein and AtMPK3 was not
      significantly changed in mutants blocked in the jasmonic acid (JA, jar1)-,
      ethylene (ein2)-, or salicylic acid (SA, pad4, npr1, and eds5)-dependent pathway.
      In contrast, expression of mRNA for the zinc finger protein was reduced in the
      mutants affected in the JA- or SA-dependent pathway.

PMID- 12236604
TI  - Regulation of Erwinia carotovora hrpL(Ecc) (sigma-L(Ecc)), which encodes an
      extracytoplasmic function subfamily of sigma factor required for expression of
      the HRP regulon.
AB  - In Erwinia carotovora subsp. carotovora (Ecc) strain 71 (Ecc71), HrpL(Ecc), an
      alternate sigma factor of the extracytoplasmic function subfamily, plays a
      central role in the expression of the hrp (hypersensitive reaction and
      pathogenicity) regulon. We document here that sigma-54 (RpoN) is required for
      full expression of hrpL(Ecc) and that HrpS, in conjunction with sigma-54,
      activates hrpL(Ecc) transcription. We also made the novel observation that
      integration host factor is required for the activation of the hrpL(Ecc) promoter.
      Our findings reveal that the RsmA/rsmB RNA-mediated post-transcriptional system,
      known to control extracellular enzyme and harpin production, affects hrpL(Ecc)
      expression as well. For example, hrpL(Ecc) RNA levels are barely detected in an
      RsmB- strain. Conversely, hrpL(Ecc) mRNA levels are much higher in RsmA- bacteria
      than in the RsmA+ parent. This effect is due to RsmA-promoted decay of hrpL(Ecc)
      RNA. Moreover, the following regulators known to control the production of either
      RsmA, rsmB RNA, or both also affect hrpL(Ecc) expression: GacA (response
      regulator of a two-component system), KdgR (an IcII type repressor), HexA (a LysR
      type repressor), RsmC (a putative transcriptional adapter). Based upon the data
      now available for Ecc and extrapolating from the evidence in other systems, we
      propose a tentative model that depicts the Hrp regulatory system of Ecc and
      explains the basis for coregulation of extracellular enzyme production and
      expression of the Hrp regulon.

PMID- 12236605
TI  - Annotation: randomised trials.
AB  - BACKGROUND: This annotation describes the uses of randomised controlled trials
      (RCTs) in clinical child psychology and psychiatry. METHOD: It explores the
      scientific basis for randomised designs, the conceptual and methodological issues
      that can arise when using them, alternative methods, and future directions.
      RESULTS: There are many issues that have to be tackled when using randomised
      trials to answer questions about the effectiveness of interventions used by child
      mental health professionals. The most important are conceptual issues concerning
      the design of these studies, practical issues, and issues about the
      interpretation of the results. There are some situations in which randomised
      trials are not possible or ideal and alternative strategies may therefore be
      needed. Future RCTs should be more explicit about whether their primary purpose
      is to further scientific knowledge or to evaluate the benefit of a treatment in
      routine clinical practice. Future trials should also have outcomes of unequivocal
      significance and be reported in accordance with standardised guidelines.
      CONCLUSIONS: Well-designed and unambiguously reported RCTs usually provide the
      best possible evidence about the effectiveness of an intervention. RCTs are not,
      however, the only way of establishing cause and effect and their results should
      always be interpreted in the light of other evidence.

PMID- 12236606
TI  - School-based indicated prevention: a randomised trial of group therapy.
AB  - BACKGROUND: One hundred and twenty-two children identified by teachers as at risk
      for behavioural or emotional problems were randomly allocated to drama-group
      therapy or to a curriculum-studies control, based in school. METHODS: One hundred
      and seventeen completed the intervention phase of the trial, which comprised 12
      hour-long sessions. Post-intervention self-reports showed significant effects
      associated with both interventions. RESULTS: However, there was a clear advantage
      of group therapy over both a waiting list control and curriculum studies,
      according to teacher reports. This was true also of categorical analyses focusing
      on those with the most severe symptoms. CONCLUSIONS: These analyses confirmed
      sustained teacher-reported improvement over a year-long follow-up period.

PMID- 12236608
TI  - Teen-aged mothers in contemporary Britain.
AB  - BACKGROUND: This paper describes the circumstances of contemporary young mothers
      and their children from a nationally representative sample, and compares them to
      the circumstances of mothers who delayed childbearing beyond age 20. METHODS: The
      participants are members of the Environmental Risk (E-risk) Longitudinal Twin
      Study, which follows an epidemiological sample of 1,116 women who became mothers
      in England and Wales in 1994-95, and their children, and contains an over-sample
      of young mothers. Home visits were conducted when the children were aged 5 years.
      Data were collected from mothers via interviews, from children via experimental
      tasks and observations, and from teachers via postal questionnaires. RESULTS:
      Young mothers encountered more socio-economic deprivation, had significantly less
      human and social capital, and experienced more mental health difficulties. Their
      partners were less reliable and supportive, both economically and emotionally,
      and were more antisocial and abusive. The children of young mothers showed
      reduced educational attainment, were rated by multiple informants as having more
      emotional and behavioural problems, were at increased risk of maltreatment or
      harm, and showed higher rates of illnesses, accidents, and injuries. CONCLUSIONS:
      Young mothers today face difficulties known to have long-lasting effects for
      women and their children. Preventions that target young mothers may reduce harm
      to the physical health, mental health, and social status of future generations.

PMID- 12236607
TI  - Nighttime sleep-wake patterns and self-soothing from birth to one year of age: a
      longitudinal intervention study.
AB  - BACKGROUND: The objectives of this study were to: (1) describe the longitudinal
      development of sleep-wake patterns of solitary-sleeping infants from 1 to 12
      months of age, (2) identify effects on sleep patterns and on self-soothing
      behaviors of introducing a novel sleep aid, and (3) identify predictive factors
      of self-soothing at 12 months using a transactional model as a guide. METHODS:
      Eighty infants' nighttime sleep-wake patterns and associated variables were
      studied at 5 times across the first year of life using videosomnography and
      questionnaires. RESULTS: Sleep-wake state developmental changes, as reported in
      investigations of infant sleep, were replicated, although a great deal of
      individual variability in the development of all sleep-related variables was
      noted. No major effects on sleep or on self-soothing behavior were evident from
      the introduction of the novel sleep aid. Three variables were identified as
      significant predictors of self-soothing at 12 months: decreasing amounts of time
      spent out of crib across the first year, high levels of quiet sleep at birth, and
      longer parental response times to infant awakenings at 3 months. CONCLUSIONS:
      These data lend preliminary support for the transactional model and suggest that
      infant and parental factors interact to influence the development of self
      soothing.

PMID- 12236609
TI  - The quality of the caregiving environment and child developmental outcomes
      associated with maternal history of abortion using the NLSY data.
AB  - BACKGROUND: Studies suggest that experiencing a perinatal loss may leave women
      vulnerable to mental health problems and may compromise parenting. Unfortunately,
      compared to miscarriages and stillbirths, very little research has examined the
      potential for grief and feelings of loss associated with elective abortion.
      Therefore, the aim of this study was to compare the quality of the childcare
      environment and children's development among children of mothers with a history
      of abortion prior to childbirth (n = 672) and children of non post-abortive women
      (n= 4,172). METHOD: Data were derived from the National Longitudinal Survey of
      Youth (NLSY), with comparisons based on two assessments of the caregiving
      environment and scores on four child outcome variables. The sample was divided
      into three child age categories: 1-4 years (n = 1,502), 5-9 years (n = 2,121),
      and 10-13 years (n = 1,524). RESULTS: After controlling for numerous potentially
      confounding socio-demographic variables, lower scores were observed for the post
      abortion group relative to the level of emotional support in the home among first
      born children in the youngest age category. Further, among 5-9-year-olds, more
      behavior problems were revealed for the children of women with a history of
      abortion. Finally, no main effects were detected between the abortion history
      groups relative to the level of cognitive stimulation in the home. CONCLUSION:
      Although it is widely recognized that at least 10% of post-abortive women
      experience negative psychological consequences, the potential effects of negative
      subjective experiences on parenting need more systematic attention.

PMID- 12236610
TI  - Correlates of expressed emotion in mothers of clinically-referred youth: an
      examination of the five-minute speech sample.
AB  - BACKGROUND: Most studies applying the adult-derived 'expressed emotion' (EE)
      measure to children have combined criticism (CRIT) and emotional overinvolvement
      (EOI). Yet, some of the parent behaviors coded as EOI and shown to have negative
      implications for parents and their adult children (e.g., multiple positive
      comments about the son or daughter) may be normative and benign for parents and
      their juvenile children. Thus, EOI, as currently operationalized, may not be
      related to child psychopathology in the way CRIT is. METHOD: We tested this
      possibility, separating CRIT and EOI and examining the individual scoring
      criteria for each in relation to psychopathology factors in a sample of 258
      clinically-referred children aged 7-17. RESULTS: Whereas each of the four CRIT
      criteria related positively to maternal reports of child psychopathology,
      especially externalizing problems, only two of the five EOI criteria were
      positively related to child psychopathology, and one (positive comments) was
      negatively related. Structural Equation Modeling findings supported a model in
      which CRIT partially mediates the relation between maternal psychopathology and
      child externalizing symptoms. CONCLUSIONS: Overall, the results suggest that EE
      may contribute to the study of parent-child relations and child psychopathology,
      but that a developmental adjustment may be required in the way EE is
      operationalized for use with juvenile samples.

PMID- 12236611
TI  - Parent-offspring resemblance for reading performance at 7, 12 and 16 years of age
      in the Colorado Adoption Project.
AB  - BACKGROUND: The study aimed to conduct the first analysis of CAP parent-offspring
      resemblance for reading performance in children aged 7, 12 and 16 years, and to
      assess the etiology of individual differences in reading performance of children
      at 16 years of age. METHOD: The Reading Recognition subtest of the Peabody
      Individual Achievement Test was administered to children in the Colorado Adoption
      Project (CAP) at 7, 12 and 16 years of age, and to their adoptive and nonadoptive
      parents when the children were 7 years of age. RESULTS: Resulting parent
      offspring correlations in adoptive families were not significant at any age, but
      correlations between scores of nonadoptive control parents and their offspring
      were significant at all three ages. CONCLUSIONS: Results obtained from behavioral
      genetic model-fitting analyses of data from parents and their children tested at
      age 16 are consistent with results of studies of twins and siblings indicating
      that individual differences in reading performance are due substantially to
      genetic influences. In contrast, environmental transmission from parents to
      offspring was negligible, suggesting that environmental influences on individual
      differences in the reading performance of children are largely independent of
      parental reading performance.

PMID- 12236612
TI  - Early childhood stunting and later behaviour and school achievement.
AB  - BACKGROUND: Stunting in early childhood is common in developing countries and is
      associated with poorer cognition and school achievement in later childhood. The
      effect of stunting on children's behaviours is not as well established and is
      examined here. METHOD: Children who were stunted at age 9 to 24 months and had
      taken part in a 2-year intervention programme of psychosocial stimulation with or
      without nutritional supplementation were reexamined at age 11-12 years and
      compared with non-stunted children from the same neighbourhoods. Their school and
      home behaviours were assessed using the Rutter Teacher and Parent Scales and
      school achievement was measured using the Wide Range Achievement Test (WRAT) and
      the Suffolk Reading Scales. RESULTS: No significant intervention effects were
      found among the stunted groups. Thus data from the four intervention groups were
      aggregated for subsequent analyses, comparing all 116 stunted children with 80
      non-stunted children. Controlling for social background variables, the stunted
      group had more conduct difficulties (p < .05) as rated by their parents. They
      also had significantly lower scores in arithmetic, spelling, word reading and
      reading comprehension than the non-stunted children (all p < .001). Conduct
      difficulties and hyperactivity were related to poorer school achievement.
      Controlling for the children's IQ, the stunted children's arithmetic scores
      remained significantly lower than those of the non-stunted children, but reading
      and spelling scores were not different. CONCLUSIONS: Previously stunted children
      had more conduct difficulties at home, regardless of their social background,
      than non-stunted children. Their educational attainment was also poorer than non
      stunted children and these results are suggestive of a specific arithmetic
      difficulty. Children with behaviour problems performed less well at school.

PMID- 12236613
TI  - The relationship between executive function abilities, adaptive behaviour, and
      academic achievement in children with externalising behaviour problems.
AB  - BACKGROUND: Specific domains of adaptive behaviours and academic achievement may,
      in part, depend on executive function capacities. Executive function deficits
      have been found to be associated with Attention Deficit Hyperactivity Disorder
      (ADHD), not Oppositional Defiant Disorder/Conduct Disorder (ODD/CD). METHOD:
      Using a sample of 110 adolescents, comprising four groups, ADHD only, co-morbid
      ADHD and ODD/CD, ODD/CD only, and a normal community control group, we assessed
      socialisation and communication skills with the Vineland Adaptive Behaviour
      Scales, along with reading ability, and executive functioning. RESULTS: Poorer
      adaptive communication skills were specifically associated with ADHD when
      compared with either ODD/CD or the control group, and the social competence of
      adolescents with ADHD was as low as the levels associated with ODD/CD. Presence
      of ADHD was associated with lower word recognition scores, while the reading
      levels of adolescents with ODD/CD were equivalent to those without behaviour
      problems. Executive function test scores correlated with all adaptive behaviour
      outcomes. Multiple regression analyses indicated that verbal ability predicted
      communication and reading scores, with executive function abilities contributing
      significant variance to the prediction in the adaptive behaviour, communication,
      and socialisation domains. CONCLUSIONS: Further research with other samples, both
      community and clinical groups, is needed to assess the generalisability of the
      findings. Small numbers of girls in the groups gave us insufficient power to
      adequately address potential gender differences.

PMID- 12236614
TI  - Comparison of male adolescent-report of attention-deficit/hyperactivity disorder
      (ADHD) symptoms across two cultures using latent class and principal components
      analysis.
AB  - BACKGROUND: The goal of this study is to gauge the consistency of Attention
      Deficit/Hyperactivity Disorder (ADHD) latent class models that are generated by
      different informants such as adolescents and parents. The consistency of
      adolescent-derived latent classes from two different samples was assessed and
      these results were then compared to the class structure generated by parent
      report ADHD information. METHODS: Self-reported DSM-IV Criterion A ADHD symptoms
      of 497 adolescent males from a population-based twin study in the state of
      Missouri (USA) were subjected to principal components and latent class analysis,
      and findings were compared to previous results obtained from identical analyses
      using an adolescent sample from Porto Alegre, Brazil (N = 483). RESULTS: The bi
      dimensional structure of self-reported ADHD symptoms was similar for both male
      adolescent groups, but explained less than 40% of the symptom variance in either
      sample. Two factors, one with loadings on inattention symptoms only and the other
      with loadings on hyperactive-impulsive symptoms only, were identified in the
      Missouri sample. Specific ADHD latent classes did not replicate well across the
      Missouri and Brazilian samples, and both groups were characterized by the
      presence of several combined symptom classes but few inattentive or hyperactive
      impulsive classes. CONCLUSIONS: While adolescent-report information across two
      different cultures can at least in part reproduce the two-factor structure of
      ADHD, results from latent class analysis suggest that adolescent reporting on
      their own symptoms is markedly different from the type of information parents
      provide about ADHD symptoms in their offspring. The current findings indicate
      that if male adolescents endorse any ADHD symptoms there is a tendency for them
      to report combined type problems.

PMID- 12236616
TI  - Interleukin 1 or tumor necrosis factor-alpha: which is the real target in
      rheumatoid arthritis?
AB  - Much debate has focused on the relative importance of interleukin 1 (IL-1) and
      tumor necrosis factor-alpha (TNF-alpha) in the pathophysiology of rheumatoid
      arthritis (RA). The production of these cytokines by synovial macrophages is
      tightly regulated by cell-cell contact with T cells. During this contact, several
      surface molecules are implicated in contact mediated cytokine production,
      including CD40 ligand, CD11b/c, and CD69. Apolipoprotein A-I, an acute phase
      reactant (APR) that declines during systemic inflammation (reverse APR), inhibits
      cytokine production by interfering in the T cell-monocyte interaction. Although
      the effects of IL-1 and TNF-alpha overlap, they have somewhat differing roles in
      RA on the basis of evidence from several animal models. TNF-alpha appears to play
      a more important role in triggering events leading to inflammation both locally
      and systemically, whereas IL-1 is more involved at the local level in processes
      leading to cartilage and bone destruction and in impeding cartilage repair.
      However, IL-1 and TNF-alpha strongly synergize in numerous biological functions,
      both in vitro and in vivo. Blockade of IL-1 and TNF-alpha simultaneously provides
      favorable effects in collagen and adjuvant induced arthritis, illustrating the
      importance of both cytokines.

PMID- 12236615
TI  - Cognitive profiles and social-communicative functioning in children with autism
      spectrum disorder.
AB  - BACKGROUND: Whether there is an unusual degree of unevenness in the cognitive
      abilities of children with autism spectrum disorder (ASD) and whether different
      cognitive profiles among children with ASD might index etiologically significant
      subgroups are questions of continued debate in autism research. METHOD: The
      Differential Ability Scales (DAS) and the Autism Diagnostic Observation Schedule
      (ADOS) were used to examine profiles of verbal and nonverbal abilities and their
      relationship to autistic symptomatology in 120 relatively high-functioning
      children with ADI-confirmed diagnoses of autism. RESULTS: Discrepancies between
      verbal and nonverbal ability scores occurred at a significantly higher rate than
      in the DAS normative sample (30%) in both a younger group of 73 children (56%)
      with a mean age of 5;5 and an older group of 47 children (62%) with a mean age of
      8;11. Discrepancies were mainly in favor of nonverbal ability in the younger
      group, but occurred equally in favor of verbal and nonverbal abilities in the
      older group. Comparison of the two age groups suggested a growing dissociation
      between verbal and nonverbal (and particularly visual processing) skills with
      age. In the older group, children with discrepantly higher nonverbal abilities
      demonstrated significantly greater impairment in social functioning, as measured
      on the ADOS, independent of absolute level of verbal and overall ability.
      CONCLUSIONS: These findings demonstrate a high rate of uneven cognitive
      development in children with ASD. Indications of a dissociation between verbal
      and visual-perceptual skills among the older children, and the specific
      association of discrepantly high nonverbal skills with increased social symptoms
      suggest that the nonverbal > verbal profile may index an etiologically
      significant subtype of autism.

PMID- 12236617
TI  - The mode of action of cytokine inhibitors.
AB  - Tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 (IL-1) are important
      mediators of inflammation and tissue damage in animal models of inflammatory
      arthritis and in patients with active rheumatoid arthritis (RA). Several
      inhibitors of these cytokines are now available for RA treatment, each having a
      different mode of action. Etanercept is a recombinant fusion protein of the
      soluble type II TNF receptor on a human IgG1 backbone, whereas infliximab is a
      chimeric anti-TNF-alpha monoclonal antibody containing a murine TNF-alpha binding
      region and human IgG1 backbone. Both agents potently and selectively bind TNF
      alpha in the cellular microenvironment, thereby preventing TNF-alpha from
      interacting with membrane-bound TNF receptors on target cells. In comparison,
      anakinra is a recombinant human IL-1 receptor antagonist (IL-1Ra) that binds
      avidly to type 1 IL-1 receptors but does not stimulate any intracellular
      responses. Studies of these agents in animal models of inflammatory arthritis
      suggest that TNF-alpha plays a more important role in promoting inflammation,
      whereas IL-1 is more important in causing cartilage and bone destruction.
      However, these differential actions have not been borne out in clinical trials,
      where TNF-alpha blockers and anakinra similarly reduce clinical signs and
      symptoms of RA as well as slow radiographic evidence of disease progression.

PMID- 12236618
TI  - Tides of inflammation: impact of biologics.
AB  - Increased knowledge about the mechanisms of joint inflammation and damage has
      profoundly shaped the development of new therapies for rheumatoid arthritis (RA).
      The first stop on this remarkable bench-to-bedside journey has been the biologics
      targeting tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 (IL-1). These
      engineered adaptations of naturally occurring molecules function to neutralize
      the biological activity of proinflammatory cytokines overproduced in the joints
      of patients with RA. The successful translation of this approach into the clinic
      has had a substantial effect on the care of patients with RA.

PMID- 12236619
TI  - Examining the efficacy of biologic therapy: are there real differences?
AB  - Biologic therapy with anakinra, etanercept, and infliximab effectively reduced
      the signs and symptoms of active rheumatoid arthritis (RA) in randomized
      controlled trials. Clinical efficacy was determined by American College of
      Rheumatology (ACR) response criteria. In patients failing previous disease
      modifying antirheumatic drug (DMARD) therapy, both anakinra and etanercept were
      significantly more effective than placebo. In patients with inadequate responses
      to methotrexate (MTX), addition of anakinra, etanercept, or infliximab to stable
      MTX therapy was significantly more effective than MTX alone. Etanercept has also
      shown efficacy in early stage, methotrexate-naive patients. Comparisons of the
      efficacy of these biologics across clinical studies are problematic due to
      differences in study design, study conduct, and patient populations. Moreover,
      ACR response rates do not allow comparisons of agents that each achieve these
      responses relative to placebo. Until comparative clinical studies are conducted,
      in which 2 biologics are evaluated using the same protocol and patient
      population, the only conclusion that can be reached from published studies is
      whether an individual biologic agent is safe and effective. All 3 biologics -
      anakinra, etanercept, and inflixmab - are effective.

PMID- 12236620
TI  - The pathogenesis of rheumatoid arthritis: pivotal cytokines involved in bone
      degradation and inflammation.
AB  - Proinflammatory cytokines, notably interleukin 1 (IL-1) and tumor necrosis factor
      alpha (TNF-alpha), play an important role in initiating and perpetuating
      inflammatory and destructive processes in the rheumatoid joint. These cytokines
      regulate many nuclear factor kappaB inducible genes that control expression of
      other cytokines, cell adhesion molecules, immunoregulatory molecules, and
      proinflammatory mediators. The expression of cyclooxygenase-2 and inducible
      nitric oxide synthase (iNOS) and thereby production of prostaglandins (PG) and NO
      are regulated by cytokines. PGE2 and NO further promote inflammation and likely
      participate in destructive mechanisms in the rheumatoid joint. In some
      experimental systems, the effects of IL-1 and TNF-alpha appear synergistic, and
      correspondingly, concomitant inhibition of both cytokines provides greater than
      additive antiarthritic effects. Although the actions of IL-1 and TNF-alpha show a
      large degree of overlap, some differences have been observed in animal models.
      However, in patients with active rheumatoid arthritis, blockade of either
      cytokine results in clinical improvement and less radiographic progression.

PMID- 12236621
TI  - What are the risks of biologic therapy in rheumatoid arthritis? An update on
      safety.
AB  - The tumor necrosis factor-alpha (TNF-alpha) blockers infliximab and etanercept
      and the recombinant interleukin 1 (IL-1) receptor antagonist anakinra are
      effective in patients with active rheumatoid arthritis (RA). Here, information in
      the medical literature and public domain is used to consider the safety of these
      biologic agents. TNF-alpha inhibition with infliximab has been associated with
      reactivation of tuberculosis and possibly development of other opportunistic
      infections (histoplasmosis, listeriosis. and pneumocystis). Exacerbations of
      multiple sclerosis and other central nervous system events have been reported
      with etanercept and infliximab. Recently, a review of preliminary data from an
      ongoing phase II study suggests that infliximab may worsen congestive heart
      failure. On the basis of clinical trials, there appears to be a higher incidence
      of serious infections seen in anakinra patients compared with controls; the
      particular combination of anakinra and etanercept may be associated with a higher
      incidence of serious infections and clinically significant leukopenia. Additional
      data are needed to understand whether all these safety issues are unique to an
      individual biologic agent or representative of a class effect. At this time,
      treating physicians must carefully weigh the benefits of these new biologics
      against their risks, particularly in patients at risk of infection.

PMID- 12236622
TI  - Preventing joint damage as the best measure of biologic drug therapy.
AB  - Joint damage occurs progressively in patients with rheumatoid arthritis (RA),
      leading to functional decline and disability. The proinflammatory cytokines
      interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) are thought to
      play a key role in promoting cartilage and bone erosion in the rheumatoid joint.
      In randomized clinical trials, inhibitors of these cytokines significantly slowed
      the rate of progressive joint damage as assessed by radiographic techniques. The
      IL-1 receptor antagonist anakinra significantly reduced erosions, joint space
      narrowing, and total joint damage when a modified Sharp score was used to
      evaluate serial hand radiographs. The maximum benefit of anakinra on joint space
      narrowing was achieved within the first 24 weeks and was maintained during
      continued treatment, whereas the slowing of erosions by anakinra increased with
      continued treatment beyond 24 weeks. In terms of TNF-alpha inhibition, infliximab
      significantly reduced joint damage in patients with long-standing RA, when used
      in combination with methotrexate (MTX), whereas etanercept significantly reduced
      erosions relative to MTX in patients with early stage disease. Comparisons among
      the cytokine inhibitors are made problematic by differences in the designs,
      patient populations, and outcome measures of these trials. Nevertheless, these
      studies demonstrate that IL-1 or TNF-alpha inhibition effectively suppresses the
      pathophysiological mechanisms associated with cartilage degradation and bone
      erosion, resulting in a slowing of further radiographic progression.

PMID- 12236623
TI  - Bone and joint destruction in rheumatoid arthritis: what is really happening?
AB  - Focal bone erosions occur at the joint margins and in subchondral bone of
      patients with rheumatoid arthritis (RA). These erosions progress throughout the
      course of disease and generally correlate with disease severity. Tissue sections
      from sites of bone erosion in the rheumatoid joint show multinucleated cells with
      phenotypic characteristics of osteoclasts, the cells responsible for resorbing
      bone during physiologic remodeling. Factors known to directly or indirectly
      induce osteoclast differentiation and activation are found in the rheumatoid
      synovium. These include receptor activator of NF-kappaB ligand (RANKL), which
      plays a critical role in osteoclast differentiation, as well as a variety of
      proinflammatory cytokines, including intereukin 1 (IL-1) and tumor necrosis
      factor-alpha (TNF-alpha), which upregulate RANKL. IL-1 also augments osteoclast
      activation, and TNF-alpha induces differentiation of early osteoclast precursors.
      In animal models of RA, RANKL is expressed at sites of bone erosion. Moreover, in
      a serum transfer model of inflammatory arthritis, animals unable to produce
      osteoclasts did not show evidence of bone resorption despite the presence of
      intense inflammation. These observations suggest that osteoclasts mediate focal
      bone erosions in RA and that targeting of osteoclasts and osteoclast mediated
      bone resorption represents a rational approach to preventing or reducing focal
      bone loss in RA.

PMID- 12236624
TI  - Evaluation of EMD 128 130 occupancy of the 5-HT1A and the D2 receptor: a human
      PET study with [11C]WAY-100635 and [11C]raclopride.
AB  - The use of so-called, atypical antipsychotic medication is becoming more
      widespread in the treatment of psychotic disorders. EMD 128 130 is a novel
      compound acting as an agonist at the 5-HT1A receptor, and as an antagonist at the
      dopamine-2 (D2) receptor. This dual action may confer additional benefits over
      selective D2 antagonists in the treatment of psychotic disorders. In this study,
      we investigated the occupancy of EMD 128 130 in vivo at the human D2 and 5-HT1A
      receptors with positron emission tomography using the radiotracers
      [11C]raclopride and [11C]WAY-100635. Seven healthy volunteers were examined
      before and after 5 days of treatment with EMD 128 130, administered in an
      incremental dose building up to 50 mg, b.d. A significant occupancy was
      demonstrated at the human D2 receptor (40% following a dose of 50 mg, b.d.) while
      there was no consistent effect observed at the 5-HT1A receptor, despite a similar
      affinity of EMD 128 130 for cloned human D2 and 5-HT1A receptors, and the
      presence of typical, central 5-HT1A agonist side-effects. The differential
      effects of EMD 128 130 at the D2 and the 5-HT1A receptor (antagonist at D2
      receptor, agonist at the 5-HTIA receptor) may explain the differences in
      occupancy observed.

PMID- 12236625
TI  - Striatal dopamine D2 receptor binding of risperidone in schizophrenic patients as
      assessed by 123I-iodobenzamide SPECT: a comparative study with olanzapine.
AB  - The aim of this investigation was to compare the degree of striatal dopamine-(D2)
      receptor blockade by two atypical antipsychotic drugs, risperidone and
      olanzapine. The percentage of D2 receptor occupancy during treatment was
      calculated by comparing the results of 123I-iodobenzamide SPECT with those from
      healthy control subjects. Twenty inpatients suffering from schizophrenia or
      schizoaffective psychosis according to DSM IV/ICD-10 criteria were treated with
      clinically recommended doses of risperidone and compared with 13 inpatients
      treated with up to 20 mg olanzapine. Neuroleptic dose and D2 receptor blockade
      correlated strongly for both risperidone (Pearson r = -0.86, p = 0.0001) and
      olanzapine (Pearson r = -0.77, p = 0.002). There was no significant difference
      between the D2 receptor occupancy of the two substances when given in the
      clinically recommended dose range (unpaired t-test, t = -0.112, p = 0.911).

PMID- 12236626
TI  - Additional dopamine reuptake inhibition attenuates vigilance impairment induced
      by serotonin reuptake inhibition in man.
AB  - There is evidence for a specific impairment of human vigilance following
      enhancement of serotonergic activity by antidepressant drugs. In the present
      study, we investigated the putative role of serotonergic-dopaminergic
      interactions in diminished vigilance by comparing the attentional effects of
      sertraline, a selective serotonin reuptake inhibitor (SSRI) with additional mild
      dopamine stimulating effects, with those of paroxetine, a SSRI without dopamine
      activity, using a placebo-controlled, double-blind, three-way cross-over design.
      Twenty-one (of 24) healthy middle-aged subjects completed the three treatment
      periods of 2 weeks in which sertraline (50 mg, days 1-7; 100 mg, days 8-14),
      paroxetine (20 mg, days 1-7; 40 mg, days 8-14) and placebo were administered.
      Vigilance (Mackworth Clock Test), selective (Stroop, Dichotic Listening) and
      divided attention (Dichotic Listening) were assessed at baseline and on days 7
      and 14 of each treatment period. Selective and divided attention were unaffected
      by SSRI treatment. Subchronic administration of paroxetine impaired vigilance
      performance at each investigated dose. Sertraline did not produce a significant
      decline in vigilance performance, presumably due to its concomitant effects on
      dopamine activity, counteracting the negative effects of serotonin on dopamine
      neurotransmission. It is concluded that a serotonergically mediated reduction of
      dopamine activity plays an important role in the reduction of human vigilance
      following SSRI administration.

PMID- 12236628
TI  - Memory performance in panic disorder patients after chronic use of clomipramine.
AB  - This study investigated the chronic use (6.3 +/- 0.5 years; mean +/- SEM) of
      therapeutic doses of clomipramine (57.0 +/- 8.0 mg/day) by outpatients with panic
      disorder/agoraphobia who were currently in remission to assess impairment of
      memory and psychomotor functions. In addition, the association between test
      performance and serum levels of clomipramine (CMI) and its active metabolite
      desmethylclomipramine (DCMI) was also assessed. Patients and healthy volunteers
      matched for sex, age and educational level were submitted to rating scales and to
      memory and psychomotor tests. There was no significant difference between groups
      regarding any variable, except for metamemory. Significant associations were
      found between (i) longer-term clomipramine treatment and poorer performance in
      the implicit test and (ii) higher serum levels of clomipramine or
      desmethylclomipramine, or both (CMI + DCMI) and lower performance in central
      executive tests and metamemory. The results showed that low doses of CMI
      chronically administered to panic patients are associated with diminished
      metamemory and impaired priming and working memory. Further investigations are
      needed to confirm these results and to determine whether the chronic use of
      higher therapeutic doses of tricyclic antidepressants is associated with more
      intense deleterious effects on memory and psychomotor functions.

PMID- 12236627
TI  - Fluoxetine treatment of depressed patients with comorbid anxiety disorders.
AB  - Major depression with comorbid anxiety disorder is associated with poor
      antidepressant outcome compared to major depression without comorbid anxiety
      disorder. The purpose of our study was to assess changes in severity of both
      depressive and anxiety symptoms in outpatients with major depression with
      comorbid anxiety disorder following fluoxetine treatment. We enrolled 123
      outpatients (mean age 38.9 +/- 10.8 years; 49% women) with major depressive
      disorder accompanied by one or more current comorbid anxiety disorders in our
      study. Patients were treated openly with fluoxetine 20 mg/day for 8 weeks.
      Efficacy assessments included the 17-item Hamilton Rating Scale for Depression
      (HAM-D) and the patient-rated Symptom Questionnaire (SQ) Scales for Depression
      and Anxiety. The mood and anxiety disorder modules of the Structured Clinical
      Interview for DSM-III-R were administered at screen and endpoint. We used 'intent
      to-treat' analysis in examining all patients assigned to treatment and completing
      the baseline visit. The mean number of comorbid anxiety disorders per patient was
      1.5 +/- 0.68. The mean HAM-D-17 score and mean Clinical Global Impressions
      Severity scores decreased significantly from baseline to endpoint (week 8)
      following fluoxetine treatment (p < 0.0001). There were significant decreases in
      all four SQ scale scores, from baseline to endpoint: depression, anxiety, somatic
      symptoms and anger-hostility (p < 0.0001). Fifty-three percent of patients (n =
      65) were depression responders (i.e. > or = 50% decrease in HAM-D-17 score at
      endpoint) and 46% (n = 57) were remitters (HAM-D-17 < or = 7 at endpoint).
      Patients with panic disorder had significantly higher baseline HAM-D-17 scores
      compared to those without panic disorder (p < 0.01). Patients with comorbid
      obsessive-compulsive disorder (OCD) were significantly less likely to be
      responders to fluoxetine at endpoint (> or = 50% decrease in HAM-D-17) and to be
      remitters (HAM-D-17 score of s 7 at endpoint) compared to patients without
      comorbid OCD (p < 0.01). Of the 41 patients on whom endpoint Structured Clinical
      Interview for DSM-III-R modules for anxiety disorders were available, 49% (n =
      20) no longer met criteria for one or more of their anxiety disorder diagnoses at
      endpoint. Our preliminary findings suggest that fluoxetine is effective in
      treating outpatients with major depression with comorbid anxiety disorders, with
      a significant effect on both depression and anxiety symptoms. Further double
      blind, placebo-controlled trials are required in larger samples to confirm our
      findings.

PMID- 12236629
TI  - Cerebrospinal fluid monoamine metabolites in cocaine patients: no relationship to
      cue-induced craving.
AB  - We aimed to examine the relationship between central monoamine metabolites and
      craving cocaine in cocaine-dependent patients. Cerebrospinal fluid (CSF)
      monoamine metabolite concentrations were determined in 20 withdrawn cocaine
      dependent patients. Patients also participated in a cue-elicited cocaine craving
      procedure. There were no significant relationships between cocaine craving scores
      and CSF concentrations of the dopamine metabolite, homovanillic acid, the
      serotonin metabolite, 5-hydroxyindoleacetic acid, or the norepinephrine
      metabolite, 3-methoxy-4-hydroxyphenylethylglycol. CSF monoamine metabolite
      concentrations were not related to cocaine craving in withdrawn cocaine-dependent
      patients.

PMID- 12236630
TI  - Acute effects of low-dose interferon-alpha on serum cortisol and plasma
      interleukin-6.
AB  - Major depression is associated with both hypothalamic-pituitary-adrenal (HPA)
      axis overactivity and immune system activation. Depression is a common occurrence
      following interferon (IFN)-a treatment. While IFN-alpha is known to stimulate the
      HPA axis, little is known about the effects of exogenous IFN-a in humans on the
      proinflammatory cytokine interleukin (IL)-6, a marker of immune system
      activation. This study examined the acute effects of IFN-alpha on cortisol and IL
      6 release, and the time course of any changes in these variables. Serum cortisol
      and plasma IL-6 were assessed in healthy volunteers over an 8-h period following
      3 million units subcutaneous IFN-alpha or placebo using a double-blind, placebo
      controlled crossover design. IFN-alpha resulted in a significant increase in both
      cortisol and IL-6. Regular sampling over 8 h did not delineate any sequential
      effect of the rise in these variables over time. We conclude that IFN-alpha
      acutely stimulates both the HPA axis and proinflammatory cytokine release. The
      hypothesis that the effect of IFN-alpha on the HPA axis is indirect and mediated
      by IL-6 was not supported by this study. Our findings are nonetheless of
      relevance to the aetiology of depression following IFN-alpha.

PMID- 12236631
TI  - Enhancement of stress-induced pituitary hormone release and cardiovascular
      activation by antidepressant treatment in healthy men.
AB  - A randomized, double-blind, placebo-controlled trial was performed to verify the
      suggestion that (i) in accordance with the results of animal studies, treatment
      with antidepressants inhibits hormone release in response to stressful
      stimulation in humans and (ii) drugs with opposing effects on brain serotonine
      (citalopram and tianeptine) exert similar modulatory effects on neuroendocrine
      activation during stress. Healthy male volunteers were treated with citalopram
      (20 mg), tianeptine (37.5 mg) or placebo for 7 days. As a stress stimulus,
      insulin-induced hypoglycaemia was used. Measurement of hormone concentrations
      revealed an enhanced release of adrenocorticotropic hormone and growth hormone in
      response to stress of hypoglycaemia in subjects treated with both antidepressants
      used. A similar augmentation was observed in systolic blood pressure. Stress
      induced prolactin release was potenciated by citalopram only. Plasma renin
      activity, epinephrine, norepinephrine and cortisol levels failed to be modified
      by antidepressants. The present study demonstrates that (i) repeated
      antidepressant treatment in healthy men does not inhibit, but enhances,
      neuroendocrine activation during stress and (ii) such effects were observed after
      treatment with antidepressants having opposing actions on brain serotonin,
      indicating involvement of nonserotoninergic mechanisms.

PMID- 12236632
TI  - The effect of glucose administration and the emotional content of words on heart
      rate and memory.
AB  - The effects of glucose administration and emotionality of target material on
      heart rate and memory were examined in a double-blind, placebo-controlled,
      balanced crossover study. Memory for neutral and emotional words was tested in 20
      young adults following a glucose drink and a placebo. Heart rate and blood
      glucose were also measured. Emotional words were recalled and recognized better
      than neutral words in both drink conditions but there was no direct effect of
      drink type on memory. During the neutral word memory tasks, similar heart rate
      deceleration was observed in both drink conditions. However, during the
      processing of emotional material, heart rates were lowered in the placebo
      condition and relatively increased in the glucose condition. These results
      further differentiate the physiological responses involved during memory for
      affective and neutral material.

PMID- 12236633
TI  - Corticosterone modulation of somatodendritic 5-HT1A receptor function in mice.
AB  - Corticosteroid modulation of serotonergic function may play a central role in
      mood disorders. 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) produces a
      hypothermia in mice that serves as an in-vivo model of somatodendritic 5-HT1A
      autoreceptor function. Daily injections (s.c.) of 50 mg/kg of corticosterone
      (CORT) for 3 days attenuates 8-OH-DPAT hypothermia tested 24 h later. This study
      sought to further clarify the nature of the CORT-mediated attenuation of
      somatodendritic 5-HT1A receptor function. Mice underwent various CORT
      manipulations prior to an 8-OH-DPAT challenge. Neither 14-day bilateral
      adrenalectomy (ADX), nor CORT 50 mg/kg/day, administered continuously by osmotic
      minipump over 72 h had any effect on the 8-OH-DPAT hypothermic response. In
      contrast, daily injections of CORT over three consecutive days caused a
      significant attenuation in 8-OH-DPAT hypothermia when tested 24 h later. However,
      administration of an additional dose of CORT 2 h prior to the 8-OH-DPAT challenge
      occluded this CORT-mediated attenuation in a dose-dependent fashion. The findings
      demonstrate that CORT modulates somatodendritic 5-HT1A receptor function in a
      complex manner. Attenuation is seen only after intermittent administration of
      CORT. In addition, the degree of attenuation depends on CORT concentrations at
      the time of testing. These findings may have implications regarding mechanisms of
      adaptation to stress.

PMID- 12236634
TI  - Repeated administration of milnacipran induces rapid desensitization of
      somatodendritic 5-HT1A autoreceptors but not postsynaptic 5-HT1A receptors.
AB  - The effects of the repeated administration of milnacipran, a serotonin (5-HT)
      noradrenaline reuptake inhibitor (SNRI), on the functional status of
      somatodendritic 5-HT1A receptors, and postsynaptic 5-HT1A receptors were explored
      using electrophysiological approaches in rats. In-vitro electrophysiological
      recordings in the dorsal raphe nucleus showed that 5-HT inhibited the firing of
      serotonergic neurones, and the selective 5-HT1A receptor antagonist, N-[2-[4-(2
      methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide (WAY
      100635), reversed the inhibitory effect of 5-HT. The potency of 5-HT to inhibit
      the firing of serotonergic neurones was slightly attenuated after 3 days of
      treatment with milnacipran (30 mg/kg, p.o., twice daily), and significantly
      attenuated after 7 or 14 days treatment at the same dose. The tricyclic
      antidepressant, imipramine, did not significantly modify the inhibitory effect of
      5-HT. After 7 days treatment at 30 mg/kg, p.o., once daily, milnacipran reduced
      the potency of 5-HT to inhibit the firing of serotonergic neurones, whereas the
      selective serotonin reuptake inhibitors, fluvoxamine and fluoxetine (60 and 30
      mg/kg, p.o., once daily, respectively), did not modify it under these conditions.
      Treatment with milnacipran (30 mg/kg, p.o., twice daily) for 14 days did not
      change the inhibition of the CA1 field potential in rat hippocampal slices by 5
      HT. These data suggest that somatodendritic 5-HT1A receptors, but not
      postsynaptic 5-HT1A receptors, rapidly desensitize in response to the repeated
      administration of milnacipran.

PMID- 12236635
TI  - Dopamine receptor mechanism(s) and morphine tolerance in mice.
AB  - Based on our previous demonstration of the involvement of dopamine-2 (D2)
      dopamine receptors in morphine antinociception, we examined the role of D2
      dopamine receptors in the expression and development of tolerance to morphine
      antinociception in mice. Tolerance to morphine antinociception was assessed by
      the tail-flick response after the administration of morphine (50 mg/kg) once
      daily for 3 days. The D2 dopamine receptor agonist, quinpirole (0.01, 0.02 and
      0.03 mg/kg), but not the D2 dopamine receptor antagonist, sulpiride (12.5, 25 and
      50 mg/kg), increased morphine antinociception in morphine non pre-exposed mice.
      The response of quinpirole was decreased by the lower doses of sulpiride. Both
      quinpirole and sulpiride decreased the expression and development of tolerance to
      antinociception induced by morphine (1.5, 3 and 6 mg/kg). The effect of
      quinpirole on the expression and development of tolerance, was reduced by a lower
      and per se non-effective dose of sulpiride. It was concluded that D2 dopaminergic
      receptors may play a part in the expression and development of tolerance to the
      antinociceptive effect of morphine.

PMID- 12236636
TI  - Donepezil for memory dysfunction in schizophrenia.
AB  - A case is reported of a 54-year-old female patient with schizophrenia and
      cognitive impairment. Her memory dysfunction improved following the addition of
      donepezil to quetiapine. The possible implications for future studies are
      reviewed.

PMID- 12236637
TI  - Moclobemide discontinuation syndrome predominantly presenting with influenza-like
      symptoms.
AB  - A case of moclobemide discontinuation syndrome who predominantly presented with
      influenza-like symptoms is presented. Sertraline treatment did not modify the
      symptoms, which may suggest different mechanisms with regard to different
      antidepressant drug discontinuation syndromes. Implications for clinical care are
      reviewed.

PMID- 12236638
TI  - The BDI of the beholder: an eye to experimental design.

PMID- 12236639
TI  - Efficacy of self-etching primers in the adhesion of 4-META/MMA-TBB resin cement
      to enamel.
AB  - PURPOSE: The effect of self-etching primer on the adhesion of tri-n-butylborane
      (TBB)-initiated resin cement to enamel has not been determined. This study
      evaluated the effectiveness of the self-etching primer by measuring the tensile
      bond strength between enamel and TBB-initiated methyl methacrylate (MMA) resin
      containing 4-methacryloxyethyl trimellitate anhydride (4-META). MATERIALS AND
      METHODS: The self-etching primers were an aqueous mixture of 30 wt%
      methacryloxyethyl phosphate, 35 wt% 2-hydroxyethyl methacrylate, and ferric
      chloride. The concentration of ferric chloride was varied from 0 to 7 wt%. The
      bovine enamel surface was treated with self-etching primer for 30 s. After
      drying, a stainless steel rod was bonded to the enamel using TBB-initiated 4
      META/MMA resin cement. The tensile bond strengths were measured after 1 day of
      immersion in 37 degrees C water and after thermal cycles between 4 degrees C and
      60 degrees C. The resin-enamel interface was observed under field-emission
      scanning electron microscopy (FE-SEM). RESULTS: The self-etching primer
      containing 5 wt% ferric chloride (Phosmer-5Fe) yielded the highest mean bond
      strength and significantly higher bond strengths than phosphoric acid etching
      after 1 day of immersion. After 5000 thermal cycles, the bond strength with
      Phosmer-5Fe was still significantly higher than that with phosphoric acid
      etching. FE-SEM images revealed tight bonding between the resin and enamel in the
      specimens of Phosmer-5Fe primer treatment. CONCLUSION: The self-etching primer
      treatment may be an alternative to phosphoric acid etching for the adhesion of
      TBB-initiated 4-META/MMA resin cement to enamel.

PMID- 12236640
TI  - Microtensile bond strength of self-etching adhesives to ground and unground
      enamel.
AB  - PURPOSE: The purpose of this study was to assess the bond strength of two self
      etching primers (SEP) to ground and unground enamel. MATERIALS AND METHODS:
      Seventy-two bovine incisors were used in this study. The buccal enamel surface of
      36 teeth was ground flat to resemble freshly cut enamel. The rest of the teeth
      were left intact. Two SEPs--Clearfil SE Bond, Kuraray (CSE) and Prompt L-Pop (3M
      ESPE) (LP)--and a conventional adhesive system, Scotchbond Multi-Purpose (3M
      ESPE) (SBMP) as a control, were used to bond a composite button to prepared and
      unprepared enamel. Microtensile test specimens were trimmed, resulting in a
      cylindrical cross-sectional area (0.21 mm2 to 0.47 mm2). These specimens were
      subjected to a tensile force at 1 mm/min until failure. Differences between
      adhesives and surface preparation were determined by two-way ANOVA. The samples
      were observed under SEM to evaluate the mode of failure. RESULTS: Bond strength
      values in MPa (SD) obtained from pooled data in descending order were: SBMP
      ground 44.54 (5.96), LP unground 42.97 (7.90), CSE unground 41.67 (11.28), LP
      ground 41.07 (12.07), CSE ground 38.56 (8.78), and SBMP unground 37.60 (9.55). No
      statistically significant differences were found (p = 0.5061) between surface
      preparation or adhesive systems. The mean in MPa (SD) of all the specimens that
      failed at the adhesive joint were: LP unground 47.13 (14.65), SBMP ground 45.28
      (7.33), CSE unground 41.40 (11.07), SBMP unground 41.1 (10.04), CSE ground 39.96
      (11.83), and LP ground 39.92 (15.45). No statistically significant differences
      were found (p = 0.5863). Failure occurred mainly at the adhesive interface.
      CONCLUSIONS: Surface preparation and adhesive treatment had no influence on resin
      composite microtensile bond strength to bovine enamel.

PMID- 12236641
TI  - Long-term durability of the dual-cure resin cement/silicon oxide ceramic bond.
AB  - PURPOSE: To determine the effects of using a ceramic primer, ceramic bonding
      agent, or a combination of primer/bonding agent on the long-term durability of
      the dual-cure resin cement/silicon oxide ceramic bond. MATERIALS AND METHODS:
      Ceramic blocks (Vita Celay Blanks), A2M, were cut into 1-, 2-, and 3-mm-thick
      slices and polished using 600-grit SiC paper. Group 1 consisted of pairs of 1-
      and 3-mm-thick slices, and Group 2 of pairs of 2- and 3-mm-thick slices. Ceramic
      surfaces were treated with 40% phosphoric acid and silanated using one of three
      treatments: (1) Clearfil Liner Bond 2V Primer (2V Pr) and Porcelain Bond
      Activator (PBA), (2) Liner Bond 2V Primer/PBA and Liner Bond 2V Bond (2V Pr +
      Bd), and (3) Clearfil Photo Bond/PBA (P Bd). They were then bonded with a dual
      cure resin cement (Panavia F) and light-cured for 20 s from each of six
      directions. After 24 h water storage at 37 degrees C, 0.7-mm-thick slabs were
      serially sectioned. Immediately thereafter, after one and six weeks, and after
      one year of water storage, two slabs were randomly selected from each subgroup
      and sliced into beams for the microtensile bond strength (microTBS) test. Data
      were evaluated with three-way ANOVA and Fisher's PLSD test (p < 0.05) and failure
      modes determined using a laser-scanning confocal microscope. RESULTS: After 1
      day, there were no significant differences between 2V Pr, 2V Pr + Bd, and P Bd (p
      > 0.05), whereas after one year, significant differences were found (p < 0.05).
      For Group 1, the micriTBS of P Bd after one year of water storage was similar to
      that after one day. In both groups, microTBS of 2V Pr and 2V Pr + Bd
      significantly decreased over time (p < 0.05), which was accompanied by an
      increase in the percentage of complete adhesive failures. CONCLUSION: The
      chemical composition of the multicomponent ceramic primer/bonding agent
      significantly affects the long-term durability of the dual-cure resin
      cement/silicon oxide ceramic bond. The presence of water in a ceramic primer has
      a significant detrimental effect on resin-ceramic bond durability. In addition,
      the thickness of the ceramic restoration influences dual-cure resin
      cement/ceramic bond durability.

PMID- 12236642
TI  - Microleakage in class II composite resin restorations: total bonding and open
      sandwich technique.
AB  - PURPOSE: The objective of this in vitro study was to evaluate gingival
      microleakage in Class II total bond resin restorations in comparison to open
      sandwich technique restorations using different materials. MATERIALS AND METHODS:
      Forty-eight human molar teeth were disinfected and stored in a 0.9% saline
      solution. In each tooth, two standardized Class II cavities (3 mm x 6 mm x 2 mm)
      were prepared with the gingival cavosurface margins located 1 mm below the
      cementoenamel junction. The teeth were divided into 4 equally sized groups (n =
      12), and the proximal boxes were treated as follows: in Group 1, no base material
      was used and the cavity was restored using SyntacSprint (SS) and Tetric Ceram
      (TC); in Groups 2, 3, and 4 the gingival portion of the cavity was restored with
      different base materials (Group 2, Dyract; Group 3, Vitremer; Group 4, Chelon
      fil) prior to the placement of the composite resin. After a storage time of 7
      days, the restorations were finished and polished. Then, specimens were submitted
      to thermocycling (500 cycles, 5 degrees C to 55 degrees C, 15 s dwell time) and
      immersed in a 0.5% methylene blue solution for 24 h. After washing, they were
      sectioned in a mesio-distal direction. Each restoration was evaluated under a
      stereomicroscope at 20x by 2 examiners and scored on a 0 to 3 scale according to
      the marginal leakage. Kappa statistics were used to evaluate the agreement
      between the examiners. Given the ordinal nature of the scoring system, data were
      submitted to a nonparametric repeated measures ANOVA. The results were confirmed
      with a parametric repeated measures ANOVA. RESULTS: Significant differences (p <
      0.001) among the four groups with respect to dye penetration were detected, with
      the association Vitremer/Tetric showing the best results. CONCLUSION: The use of
      Vitremer in the open sandwich technique presents the lowest degree of
      microleakage among the treatments considered in this study.

PMID- 12236643
TI  - The influence of occlusal finish line configuration on microleakage of indirect
      composite inlays.
AB  - PURPOSE: The aim of this in vitro study was to evaluate the influence of occlusal
      finish line configuration on microleakage of indirect composite inlays. MATERIALS
      AND METHODS: Forty-five recently extracted premolars were randomly assigned into
      three groups with different types of occlusal finish line preparations: bevel,
      chamfer, and butt joint. All restorations were made in Artglass (Heraeus Kulzer)
      and luted according to the manufacturer's recommendations. The teeth were sealed
      and then thermocycled 500 times between 5 degrees C and 55 degrees C. After that
      they were immersed in a 2% methylene blue (pH 7.2) solution for 24 hours. Each
      tooth was bisectioned in the buccal/lingual direction and then examined
      microscopically at each section to evaluate the microleakage score. The data were
      analyzed with chi-square and Fisher's Exact tests. RESULTS: There were no
      significant differences between the buccal margins of maxillary premolars with
      occlusal bevel or butt joint; the chamfer had the worst performance. In the
      buccal margin of mandibular premolars, the bevel and chamfer showed significantly
      smaller amounts of leakage than the butt joint. No significant differences were
      observed between the three types of occlusal cavosurface preparations in the
      lingual margin of maxillary and mandibular premolars. CONCLUSIONS: The finish
      line configuration, the position of the teeth in the arch, and the margin (buccal
      vs lingual) influenced microleakage. Whenever microleakage was observed in this
      study, it was always observed at the tooth-cement interface.

PMID- 12236644
TI  - In vivo long-term durability of the bond to dentin using two adhesive systems.
AB  - PURPOSE: The objective of this work was to evaluate the in vivo long-term
      durability of bond strength and morphological appearance of interfaces between
      dentin and two adhesive systems. MATERIALS AND METHODS: Class V cavities were
      prepared on the facial surfaces of 6 intact teeth of a monkey, and restored with
      Unifil Bond/Unifil F and Fuji Bond LC/Clearfil AP-X. One year later, 10 other
      teeth were restored with the same materials and the monkey was sacrificed after
      24 hours. For in vitro examination, 6 more teeth were extracted from the monkey,
      restored in a similar manner with the two materials, and stored in 37 degrees C
      water for 1 day. All specimens were subjected to the microtensile bond strength
      (microTBS) test. The debonded surfaces of specimens were morphologically observed
      with the FE-SEM. RESULTS: There were no statistically significant differences
      among the mean microTBS obtained for Unifil Bond/Unifil F under the three
      conditions (1 day and 1 year in vivo, and 1 day in vitro), and most specimens
      showed cohesive failure within resin composite (Unifil F). However, FE-SEM
      observations showed that resinous material within the hybrid layer made by Unifil
      Bond seemed to increase in porosity after 1 year. For Fuji Bond LC/Clearfil AP-X,
      pTBS at 1 day in vitro was significantly higher than that at 1 year in vivo, and
      bond strengths in vivo tended to decrease over time, although a statistically
      significant difference was not observed. From FE-SEM observations, most specimens
      showed cohesive failure within the adhesive (Fuji Bond LC). CONCLUSION: Bond
      strengths of the two adhesive systems tended to decrease for 1 year in vivo.

PMID- 12236645
TI  - Is the dentist of the future an oral precision engineer?

PMID- 12236646
TI  - Dental adhesives of the future.
AB  - The current trend in the development of dentin adhesives attempts to simplify
      bonding steps and make them more user-friendly. However, optimizing speed and
      efficiency should be accomplished without major tradeoffs in the quality or
      durability of resin bonds. Although dentin adhesives have improved tremendously
      over the past decade, postoperative sensitivity, incomplete marginal seal,
      premature bond degradation, biocompatibility, and compromised bonding to abnormal
      substrates are still considered potential problems associated with their use.
      Advances in different scientific disciplines will enrich the pool from which
      ideas may be drawn in designing future dentin adhesives. It is probably on the
      molecular level that we will see the greatest expansion of horizons. With the
      advances in biomimetics, future dentin adhesive monomers may contain domains
      derived from protein-based, underwater bioadhesives secreted by aquatic animals
      such as mussels and barnacles, making them less dependent on the surface energy
      of the bonding substrates as well as less susceptible to hydrolytic degradation.
      As adhesive joints produced by contemporary adhesives are brittle in nature,
      future adhesive design may incorporate biomimetic intermediate-strength domains
      that can undergo stepwise reversible unfolding in response to varying functional
      stress levels before ultimate catastrophic failure of the adhesive joint occurs.
      These domains may also re-establish folded configurations on stress relaxation,
      making the adhesive both strong and tough. Using the concept of controlled
      release, future adhesives may contain fluorescent biosensors that can detect pH
      changes around leaking restorations. They may even have the capacity to heal
      autonomously, in response to microcracks formed by functional stresses within the
      adhesive joint. The ability to self-diagnose and self-repair will increase the
      life expectancy of adhesive restorations. Future dentin adhesives may also assume
      a more instrumental role in therapeutics apart from caries prevention. These
      features may include the controlled release of noncollagenous proteins to promote
      remineralization of collagen matrices in sound and caries affected dentin, and
      growth factors to induce controlled formation of reparative dentin.

PMID- 12236647
TI  - The prevalence of musculoskeletal symptoms among British Columbia sonographers.
AB  - A survey (n = 211, 92% response rate) was carried out to determine baseline
      prevalence of musculoskeletal symptoms and identify related biomechanical,
      psychosocial, work organization and demographic factors among the population of
      sonographers in British Columbia, Canada. Ninety-one percent of respondents
      reported musculoskeletal pain or discomfort that they associated with the work
      tasks of scanning. Almost half reported frequent and severe symptoms. The neck,
      shoulder, and upper back were the main symptomatic body sites. A very small
      minority were absent from work due to the symptoms, with more than two thirds of
      respondents reporting working in pain. Bivariate analyses found significant
      associations between scanning time, static postures, psychosocial factors, and
      degree of musculoskeletal symptoms.

PMID- 12236648
TI  - The role of the New Zealand forest industry injury surveillance system in a
      strategic ergonomics, safety and health research programme.
AB  - Forestry is among the most hazardous of all industry sectors internationally. In
      New Zealand, highest work-related morbidity and mortality incidence rates are
      found in the logging sector. The New Zealand Forest Industry Accident Reporting
      Scheme (ARS) is a forestry injury surveillance system maintained by the Centre
      for Human Factors and Ergonomics (COHFE). The paper highlights the pivotal role
      of an industry-wide injury surveillance system in an industry-specific strategic
      research programme, giving examples of the use of ARS data in identification of
      priority areas for ergonomics, safety and health research attention, for safety
      awareness feedback to the industry, and in the evaluation of injury
      countermeasures. An analysis of injury patterns and trends for one high-risk
      forestry operation (skid work) is presented to illustrate both the capabilities
      and limitations of the ARS in its present stage of development.

PMID- 12236649
TI  - Estimating energy expenditure in wildland fire fighters using a physical activity
      monitor.
AB  - This study piloted the use of an electronic activity monitor (MTI AM 7164-1.2) as
      a tool for estimating activity (EE(ACT), kcal day(-1)) and total (EE(TOT) kcal
      day(-1)) energy expenditure in wildland fire fighters during extended periods of
      wildland fire suppression. Ten Hot Shot fire fighters (9 men, 1 woman)
      volunteered to wear a MTI monitor during every work shift for 21 consecutive
      days. Summarizing whole-body motion data each 1 min, the raw activity data
      (counts min(-1)) were transformed into units of kcal min(-1) using a custom
      computer program with standard conversion equations. EE(TOT) averaged (Mean+/-SD)
      4768+/-478 kcal day(-1), while EE(ACT) averaged 2585+/-406 kcal day(-1), neither
      of which differed significantly (P = 0.198 and 0.268, respectively) from
      literature values reported for Hot Shots using the doubly labeled water
      technique. These data suggest that the electronic activity monitor provided
      reasonable estimates of EE in wildland fire fighters. This study should be
      verified, however, with a more complete validation methodology to ensure these
      findings.

PMID- 12236650
TI  - Head posture and loading of the cervical spine.
AB  - Calculations by Colombini et al. (Ergonomics of Working Postures. Taylor &
      Francis, London, 1985) showed that a line of gaze below the horizontal would load
      the cervical spine more than a horizontal gaze. Precision stadiometer tests were
      run, using seven subjects, to measure the effects on spinal length of different
      angles of gaze. After 1 h exposure whilst sitting in a controlled posture, there
      were significant differences in the shrinkage of the spine between the horizontal
      gaze and the 20 and 40 angles below the horizontal. The increased spinal loading
      demonstrated by the increase in spinal shrinkage calls into question the
      recommendations for angle of gaze recommended in textbooks.

PMID- 12236651
TI  - A methodology for evaluating the usability of audiovisual consumer electronic
      products.
AB  - Usability evaluation is now considered an essential procedure in consumer product
      development. Many studies have been conducted to develop various techniques and
      methods of usability evaluation hoping to help the evaluators choose appropriate
      methods. However, planning and conducting usability evaluation requires
      considerations of a number of factors surrounding the evaluation process
      including the product, user, activity, and environmental characteristics. In this
      perspective, this study suggested a new methodology of usability evaluation
      through a simple, structured framework. The framework was outlined by three major
      components: the interface features of a product as design variables, the
      evaluation context consisting of user, product, activity, and environment as
      context variables, and the usability measures as dependent variables. Based on
      this framework, this study established methods to specify the product interface
      features, to define evaluation context, and to measure usability. The
      effectiveness of this methodology was demonstrated through case studies in which
      the usability of audiovisual products was evaluated by using the methods
      developed in this study. This study is expected to help the usability
      practitioners in consumer electronics industry in various ways. Most directly, it
      supports the evaluators' plan and conduct usability evaluation sessions in a
      systematic and structured manner. In addition, it can be applied to other
      categories of consumer products (such as appliances, automobiles, communication
      devices, etc.) with minor modifications as necessary.

PMID- 12236652
TI  - Food and drink packaging: who is complaining and who should be complaining.
AB  - This paper reports a questionnaire survey of shoppers at four supermarket stores
      in the UK. Regression analyses were used to determine factors in consumer
      complaints with the packaging of food and drink products. Neuroticism and
      treatment in hospital for an accident involving packaging in the last 3 years
      were significant associates. Analyses on who was most likely to suffer accidents
      or injuries while opening food and drink packaging indicated that handedness
      (that is, being left handed made accidents more likely) and scoring low on a
      measure of personal control during decision-making were significant associates.
      Analyses on who suffered the most serious accidents and injuries whilst opening
      food and drink packaging revealed that the decision-making style of social
      resistance (that is, the extent to which you resist asking for help from others)
      was related to susceptibility to the most severe accidents. These findings imply
      that individual factors (including both personal characteristics and personality
      traits) should be taken into account when considering the openability of
      packaging. The results of this study indicate that manufacturers should ensure
      that novel packaging closures have been tested on left handers in order to
      discover any unique difficulties for this sub-group, that packaging opening tools
      specifically for left-handed people should be made available and that
      manufacturers of packaging should always look at a 'worst case scenario' for
      their packaging closures as it is evident that some people will continue to
      struggle with difficult packaging until either they open it or they have injured
      themselves.

PMID- 12236653
TI  - Participatory ergonomics applied in installation work.
AB  - This paper evaluates a step-by-step participatory approach to better work,
      applied in reducing the musculoskeletal workload in installation work. To arrive
      at a reduction in workload, a steering group led the project through the
      following steps: 1. INTRODUCTION: defining the goal and informing all 7000
      employees. 2. ANALYSIS: finding major loading tasks. 3. Solution phase: creating
      solutions in group sessions and prioritise. 4. TESTING: promising solutions were
      tested during real operations. 5. Implementing: spreading the knowledge through
      the whole company and asking for additional solutions. 6. EVALUATION: the effect
      and process were evaluated. The result was that 138 devices were bought. Seven
      out of nine devices were used daily. Users reported a good or very good reduction
      in musculoskeletal loading and were satisfied. The project was cost-effective
      within 1 year. Adding organizational measures or system solutions could have
      increased the effect, and more direct participation could have increased the
      impact. The first steps (introduction, analysis of work, solution generation and
      user tests) were well organized and contributed to the success. The processes in
      the last steps were unstructured and the evaluation was not representative. Sixty
      additional devices were suggested by employees of which 12 were selected. These
      devices seemed a success, but no data could be obtained on the use and experience
      with these solutions.

PMID- 12236654
TI  - On complexity, process ownership and organisational learning in manufacturing
      organisations, from an ergonomics perspective.
AB  - The paper discusses some characteristics and implications of the complexity
      approach as applied to manufacturing organisations and their supply chains. It
      then discusses the acquisition of process capability within organisations, one of
      the essential processes for maintaining the organisation's ability to compete in
      a complex environment. The paper then discusses the concept of the Process Owner,
      as a means of preserving and evolving the organisation's knowledge under such
      circumstances, and discusses the consequences of this role. Finally, the
      knowledge lifecycle management implications are discussed, since these are among
      the resources that a Process Owner will require to maintain the effectiveness of
      the role. Throughout the paper the point is made that complexity demands more of
      an organisation than technical excellence; technology alone will not overcome the
      effects of complexity and the organisation's people must be included in the
      response to its challenges.

PMID- 12236655
TI  - Reliability and validity of self-reported assessment of exposure and outcome
      variables for manual lifting tasks: a preliminary investigation.
AB  - The reliability and validity of self-reported assessment of exposure and outcome
      variables were examined for manual lifting activities among ten physiotherapists.
      In this study, the participants evaluated the effects of five lifting variables
      on perceived effort, twice separated by a one-week period. One hundred and sixty
      two lifting conditions were evaluated by each subject. The exposure and outcome
      lifting variables were described in linguistic terms. Intra-class correlation
      coefficient (ICC(1,1)) analysis revealed a mean value of 0.62 for all lifting
      activities. The self-reported assessment was cross-validated with the NIOSH
      lifting index by mapping the linguistic variables into numerical ranges. Moderate
      correlations (r = 0.54 and 0.53, p<0.01) were obtained between perceived physical
      exertion/perceived risk and lifting index. The findings of this study provide
      preliminary indications that human-based methodologies may be further explored on
      experienced workers.

PMID- 12236656
TI  - Increase in spinal stability obtained at levels of intra-abdominal pressure and
      back muscle activity realistic to work situations.
AB  - In this study, sudden load was applied to the trunk and situations with
      alternating low levels of intra-abdominal pressure (IAP) realistic to work
      situations were compared. The aim was to see if IAP and the small increases in co
      contraction of back muscles that follow are capable of increasing the stiffness
      of the lumbar spine. Nine subjects participated in ten sudden load situations
      during which they were asked to hold a box and conduct a percentage of maximal
      IAP. The hip was fixed and the load was applied horizontally on the trunk. EMG,
      IAP, and movement of the trunk were measured. It was found that IAP of a size
      likely to appear in work situations, and the concomitant increase in muscle co
      activation increased the spine stiffness. This increase in stiffness decreased
      the movement caused by the sudden load. These results show that both abdominal-
      and back muscles may have an important role in stabilising the spine, and in
      decreasing movements caused by sudden loads likely to appear in numerous work

PMID- 12236657
TI  - A comparison of the effects of floor mats and shoe in-soles on standing fatigue.
AB  - In assembly line positions and other occupations, employees experience pain and
      discomfort associated with long periods of standing. Modifying flooring is a
      common intervention method used to alleviate problems associated with constrained
      standing. This study investigated the effects of four different standing
      conditions upon assembly workers' perception of general fatigue and discomfort
      associated with various body parts following 1 week of 8-h days of exposure to
      each condition. The four standing conditions were (1) on hard floor, (2) on a
      floor mat, (3) wearing shoe in-soles, and (4) wearing shoe in-soles while
      standing on a floor mat. Questions were asked regarding general fatigue and
      discomfort. In general, the mat, in-soles and combined conditions were more
      comfortable than standing on hard floor. Moderately strong correlations were
      found for the variables of height, age and job tenure. Shorter individuals
      experienced greater discomfort in the upper leg and low back when standing on a
      mat and when wearing in-soles. The older workers and those with more job
      seniority reported greater discomfort associated with body joints when standing
      on the hard floor and when standing on the floor mat. No significant differences
      in fatigue or discomfort were found when comparing the overall effects of using
      the floor mat to wearing the shoe in-soles or the combined condition.

PMID- 12236658
TI  - Oxygen consumption, heat production, and muscular efficiency during uphill and
      downhill walking.
AB  - Oxygen consumption, heat production, and muscular efficiency for walking are
      parameters important to know for ergonomics models and equipment design. Most of
      these assume that the oxygen consumption and heat production of downhill walking
      are the same as for uphill walking. Eight subjects wearing insulating clothing
      walked on a treadmill at three uphill and three downhill grades, and at level
      grade at a rate of 1.1 m/s. Oxygen consumption VO2 was calculated from steady
      state measurements of respiratory minute volume and oxygen percentage. Heat
      production (q) was calculated from the rate of heat storage in the body and
      clothing. Least-squares best fit equations for oxygen consumption and heat
      production found were to be VO2 = 0.813 + 0.0361G + 0.000810G2 - 0.0000302G3 and
      q = 6.55 + 0.185G + 0.0114G2 - 0.000190G3 where G is percent grade.
      Approximations show that VO2 (downhill) = 0.5 VO2 (uphill), q (downhill) = 0.67 q
      (uphill), and muscular efficiency eta (downhill) = -2eta (uphill).

PMID- 12236659
TI  - Ergonomics study on the handle length and lift angle for the culinary spatula.
AB  - The culinary spatula (turning shovel) is one of the most common cooking tools
      used in the kitchen in Asia. However, the culinary spatula has seldom been
      ergonomically investigated. When a person uses a spatula to cook food, the
      operations involve repetitive bent-wrist motions, such as dorsiflexion, palmary
      flexion, and radial and ulnar deviations. These movements may cause cumulative
      trauma disorders in the upper extremities, and in particular carpal tunnel
      syndrome. A poorly designed culinary spatula will be ergonomically inefficient
      and cause injury to the hand and wrist. The purpose of this study was to
      investigate the effects of spatula handle length and lift angle on food-frying,
      food-turning, and food-shoveling performance. Eight female subjects were tested
      using 16 different culinary spatulas, with four different handle lengths (20, 25,
      30 and 35 cm) and four different lift angles (15 degrees, 25 degrees, 35 degrees
      and 45 ). The criterion measures included cooking performance, and rating of
      perceived exertion. The subjects ranked their preference after all of the tasks
      in the tests were completed. The results showed that: (1) The handle length had a
      significant influence on the cooking performance, and rating of perceived
      exertion. The optimal handle lengths for frying food, turning food, and shoveling
      food were 20, 25 and 25 cm, respectively. (2) The lift angle significantly
      affected the cooking performance, and rating of perceived exertion. The optimal
      lift angles for frying food, turning food, and shoveling food were 15 degrees, 15
      degrees and 25 degrees, respectively. (3) Both the handle length and lift angle
      had significant effects on subjective preference. For the handle length, the 20
      cm length was the best. For the lift angle, the 25 angle was the best. (4) In
      general, a spatula with a 20 cm handle length and 25 degrees lift angle was the
      best. A spatula with a 25 cm handle length and 15 lift angle was the second most
      preferred. (5) However, to prevent subjects from touching the edge of a hot pan,
      a spatula with a 25 cm handle length and 25 lift angle is suggested.

PMID- 12236660
TI  - Development of grain threshers based on ergonomic design criteria.
AB  - Threshers are used extensively on Indian farms for threshing grains, but are
      involved in a significant proportion of limb crush injuries. International safety
      standards are somewhat difficult to enforce because manufacture of machines is
      done at widely dispersed local workshops. Locally made machines are used for crop
      production and post-harvesting operations, with a great deal of manual work. This
      technical note reports the results of a study to develop a cost effective,
      improved design for safe operation of threshers based on ergonomic principles.

PMID- 12236661
TI  - Maternal and child health graduate and continuing education needs: a national
      assessment.
AB  - OBJECTIVES: The purpose of this report is to describe the methodology and results
      of a recent national assessment of long-term graduate and short-term continuing
      education needs of public health and health care professionals who serve or are
      administratively responsible for the U.S. maternal and child health population
      and also to offer recommendations for future training initiatives. METHODS: The
      target of this needs assessment was all directors of state MCH, CSHCN and
      Medicaid agencies, as well as a 20% random sample of local public health
      departments. A 7-page needs assessment form was used to assess the importance of
      and need for supporting graduate and continuing education training in specific
      skill and content areas. The needs assessment also addressed barriers to pursuing
      graduate and continuing education. Respondents (n = 274) were asked to indicate
      the capacity of their agency for providing continuing education as well as their
      preferred modalities for training. RESULTS: Regardless of agency type, i.e.,
      state MCH, CSHCN, Medicaid or local health department, having employees with a
      graduate education in MCH was perceived to be of benefit by more than 70% of the
      respondents. Leadership, systems development, management, administration,
      analytic, policy and advocacy skills, as well as genetics, dentistry, nutrition
      and nursing, were all identified as critical unmet needs areas for professionals
      with graduate training. Education costs, loss of income, and time constraints
      were the identified barriers to graduate education. More than 90% of respondents
      from each agency viewed continuing education as a benefit for their staff,
      although the respondents indicated that their agencies have limited capacity to
      either provide such training or to assess their staffs need for continuing
      education. Program managers and staff were perceived in greatest need of
      continuing education and core public health skills, leadership, and
      administration were among the most frequently listed topics to receive continuing
      education training support dollars. Time away from work, lack of staff to cover
      functions, and cost were the top barriers to receiving continuing education.
      While attending on-site, in-state, small conferences was the continuing education
      modality of first preference, there was also considerable interest expressed in
      web-based training. CONCLUSIONS: Six recommendations were developed on the basis
      of the findings and address the following areas: the ongoing need for continued
      support of both graduate and continuing education efforts; the development of a
      national MCH training policy analysis center; the incorporation of routine
      assessments of training needs by states as part of their annual needs
      assessments; the promotion of alternative modalities for training, i.e., web
      based; and, the sponsorship of academic/practice partnerships for cross-training.

PMID- 12236662
TI  - Physical activity and risk of neural tube defects.
AB  - OBJECTIVE: Owing to its association with known risk factors for neural tube
      defects (NTDs) and its impact on physiologic processes relevant to fetal
      development, physical activity was identified as a potential risk factor for NTD
      affected pregnancy. METHODS: Using data from a population-based case-control
      study of deliveries occurring in California from 1989 to 1991, we estimated the
      potential risk of having an NTD-affected pregnancy associated with variation in
      maternal physical activity. In-person interviews were conducted with 538 (88% of
      eligible) mothers of NTD cases and with mothers of 539 (88%) nonmalformed
      controls on average 5 months from the term delivery date. An index reflecting
      reported frequency and exertion level for six activity groups (e.g., jogging and
      running) was used to summarize each woman's physical activity level in the
      periconceptional period. RESULTS: Unadjusted analyses indicated that compared to
      women considered inactive by this index, physically active women had 30-50% lower
      risk for NTD-affected pregnancies. After adjustment for several potential
      confounders and an evaluation of potential effect modification, results suggested
      that the association was restricted to women who did not take
      multivitamin/mineral supplements during the periconceptional period. Excluding
      mothers with reported medical problems did not substantially alter findings.
      CONCLUSIONS: This study suggests that the benefits of physical activity may
      extend to reduction of NTD risk among certain subgroups of women.

PMID- 12236663
TI  - The association among adolescents' tobacco use, their beliefs and attitudes, and
      friends' and parents' opinions of smoking.
AB  - OBJECTIVE: To examine adolescents' attitudes toward smoking, the presence of a
      false consensus effect, and the influence of peer and parental attitudes about
      smoking choices on being a susceptible, never smoker; an experimenter; and a
      current smoker. METHODS: Data from The Robert Wood Johnson Foundation's 1996
      National Study of Tobacco Price Sensitivity, Behavior, and Attitudes Among
      Teenagers and Young Adults (RWJF survey) were used to produce national estimates
      of the tobacco use behaviors and attitudes of adolescents enrolled in high
      school. Three logistic regression models were estimated to examine which
      psychosocial variables were associated with three different stages of smoking
      uptake. RESULTS: Positive attitudes toward tobacco use were associated with a
      greater likelihood of being a susceptible, never smoker (OR = 1.50), an
      experimenter (OR = 1.27), and a current smoker (OR = 2.96). Those respondents who
      believed that 50% or more of all adolescents smoked were more likely to be
      current smokers (OR = 1.45). The importance of the opinions of one's friends and
      parents about his/her choice to smoke was also found to be associated with
      smoking behavior. CONCLUSIONS: Preventing the initiation and continuation of
      smoking among adolescents will require interventions that address individual
      attitudes with respect to tobacco and will also need to present a clear picture
      of adolescent smoking. In addition, prevention and intervention messages should
      emphasize the importance of parental opinions on youth tobacco use regardless of
      parental tobacco use behavior.

PMID- 12236664
TI  - Reliability of birth certificate data: a multi-hospital comparison to medical
      records information.
AB  - OBJECTIVE: To examine the reliability of birth certificate data and determine if
      reliability differs between teaching and nonteaching hospitals. METHODS: We
      compared information from birth certificates and medical records in 33,616 women
      admitted for labor and delivery in 1993-95 to 20 hospitals in Northeast Ohio.
      Analyses determined the agreement for 36 common data elements, and the
      sensitivity, specificity, and positive and negative predictive values of birth
      certificate data, using medical record data as a "gold standard." RESULTS:
      Sensitivity and positive predictive value varied widely (9-100% and 2-100%,
      respectively), as did agreement, which was "almost perfect" for measures of prior
      obstetrical history, delivery type, and infant Apgar score (K = 0.854-0.969) and
      "substantial" for several other variables (e.g., tobacco use (K = 0.766),
      gestational age (K = 0.726), prenatal care (K = 0.671)). However, agreement was
      only "slight" to "moderate" for most maternal risk factors and comorbidities (K =
      0.085-0.545) and for several complications of pregnancy and/or labor and delivery
      (K = 0.285-0.734). Overall agreement was similar in teaching (mean K = 0.51) and
      nonteaching (K = 0.52) hospitals. Although agreement in teaching and nonteaching
      hospitals varied for some variables, no systematic differences were seen across
      types of variables. CONCLUSIONS: Our findings indicate that the reliability of
      birth certificate data vary for specific elements. Researchers and health
      policymakers need to be cognizant of the potential limitations of specific data
      elements.

PMID- 12236665
TI  - Unintended pregnancy in a commercially insured population.
AB  - OBJECTIVES: While much attention has been focused on unintended pregnancy in
      disadvantaged populations, few studies have focused on women in lower risk
      groups. This study, conducted in a national managed care organization, reports
      the prevalence of unintended pregnancy resulting in live births and examines
      associated factors METHODS: Women ages 18-49 who delivered a live infant during a
      6-month interval were eligible for the study. Telephone surveys were conducted
      after delivery. We report the rate of unintended pregnancy resulting in a live
      birth, and describe its association with sociodemographic and pregnancy-related
      factors, partner's intention status, and contraceptive use. RESULTS: Of 1173
      births, 29% were unintended. Women who reported that the partner did not want the
      pregnancy were 7.4 times more likely than women whose partner wanted the
      pregnancy to regard the pregnancy as unintended. Only 40% of the women with an
      unintended birth used birth control and 64% of those used less effective methods
      such as condoms and diaphragms. CONCLUSIONS: In a population where the majority
      of women were married, educated, and with incomes over $40,000, almost 1/3 of the
      births resulted from unintended pregnancies. Future research is needed to help us
      better understand contradictions in pregnancy intention and contraceptive
      behavior. Comprehensive efforts are needed to promote consistent and correct use
      of contraception by women at risk for unintended pregnancy, and to involve male
      partners in family planning.

PMID- 12236666
TI  - A longitudinal study of risk factors for otitis media in African American
      children.
AB  - OBJECTIVE: Otitis media with effusion (OME) is a common health care problem for
      children. The purpose of this study was to examine factors that place children at
      risk for OME such as age, type of child care, number of people in the household,
      and smoking in the household. METHODS: Eighty-six African American children,
      enrolled in center-based child care in infancy, entered the study at a mean age
      of 8.2 months and were followed prospectively until 48 months of age. Ear status
      was documented biweekly using pneumatic otoscopy and tympanometry. Data on risk
      factors were collected every 6 months. RESULTS: Results indicated that children
      had a marked decrease in the proportion of time with OME between 6 and 48 months.
      The rate of OME decline was faster in the first 2.5 years than in subsequent
      years. Children in center-based child care showed a slightly slower rate of
      decline than did children in non-center-based care. Longitudinal analysis
      indicated that the age of the child and the number of other children in the
      household were significant predictors of OME. For each additional child under 12
      years of age in the home, there was a 2% increase in the proportion of time with
      OME. CONCLUSION: While attendance in group child care predicted a risk for OME,
      children's age and the number of other children in the household were still
      contributing risk factors for OME.

PMID- 12236667
TI  - Introducing domestic violence assessment in a postpartum clinical setting.
AB  - OBJECTIVES: Attempts to introduce assessment for exposure to domestic violence in
      health care settings have met with limited success, in spite of widespread
      knowledge of the prevalence of spousal abuse and its implications for women's
      health. We assessed the utility of Rogers' model of institutional change for the
      implementation of a universal screening program for domestic violence in
      postpartum clinical settings. METHODS: We adapted Rogers' innovation-diffusion
      model to develop and implement a protocol for domestic violence assessment among
      300 nurses working in two hospitals that together provide obstetrical care to the
      City of Vancouver, British Columbia, Canada. Our education sessions introduced
      new knowledge and addressed attitudes and beliefs. They were followed by "hands
      on" demonstration and supervision of assessments. Our "Let's Talk" visual aids
      program added visibility to our initiative and provided cues as to how to
      undertake screening and response. Screening rates were monitored along with a
      process evaluation based on anecdotal reporting by nursing staff. RESULTS:
      Following the initiation of educational sessions and supervision of assessment,
      the screening rate was 42%. Within 6 months, the screening rate had climbed to
      60% and was sustained at that level. Major barriers to screening include
      difficulty in finding the opportunity to screen in privacy and overcoming
      language barriers. CONCLUSIONS: Application of Rogers' principles of diffusion of
      innovation in the implementation of a universal program for a domestic violence
      in two obstetrical care settings resulted in a screening rate of 60% which has
      been sustained for the first 18 months of the program.

PMID- 12236668
TI  - A search for guidance: examining prenatal substance exposure protocols.
AB  - OBJECTIVES: To describe key elements of a set of hospital prenatal substance
      exposure protocols, and to relate variations in protocol content to the state
      legislative environment and hospital characteristics. METHODS: Nurse managers and
      hospital administrators with responsibility for perinatal care were asked to
      provide their hospital's prenatal substance exposure protocol. Using a structured
      coding form, two independent coders read and abstracted information from the 87
      protocols received. Hospital and patient characteristics and the state's legal
      environment were cross-tabulated. RESULTS: Only half of coded protocols included
      an implementation date; 37% lacked any goal or statement of purpose. Most covered
      the key components of prenatal substance exposure management, such as
      precipitants and guidelines for toxicology screening, but failed to present their
      contents clearly. Only a few discussed whether specific maternal consent is
      required for a maternal or a newborn toxicology screen. Protocols from states
      that had made some legislative response to prenatal substance exposure were more
      likely to provide reporting guidelines and a discussion of consent for a
      toxicology screen for mothers and newborns. Protocols were more likely to be
      found in larger hospitals and were more detailed in hospitals serving more
      affluent and less minority patient populations. CONCLUSIONS: More attention needs
      to be devoted to the development of prenatal substance exposure protocols, as
      their lack of clarity precludes most from meeting protocol development goals,
      such as encouraging standardized care. Associations between hospital
      characteristics, state legislative environment and protocol features suggest that
      legislative mandates could shape their development and features.

PMID- 12236670
TI  - Characterization of essential oils from lamiaceae species by fourier transform
      Raman spectroscopy.
AB  - The Fourier transform Raman (FT-Raman) spectra of pure terpenes and essential
      oils obtained by hydrodistillation of some Lamiaceae species, are presented. This
      study shows that principal components of an essential oil can be recognized by FT
      Raman. Components predicted by FT-Raman spectrum of an essential oil correlate
      well with those found as major constituents by GC-MS. In this way the basic
      chemical character of an essential oil can be recognized. The results demonstrate
      that certain Raman intensities can be correlated to specific terpenes and
      therefore FT-Raman can discriminate between the essential oils of which main
      components belong to different classes of compounds.

PMID- 12236671
TI  - Identification of protein degradation during post-mortem storage of pig meat.
AB  - Eighteen proteins and peptides that were found to change post-mortem in
      Longissimus dorsi from pig muscle were identified by the use of matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry. The 18 peptides
      originate from 9 different proteins including the 3 structural proteins (actin,
      myosin heavy chain, and troponin T) and the 6 metabolic proteins glycogen
      phosphorylase, creatine kinase, phosphopyruvate hydratase, myokinase, pyruvate
      kinase, and dihydrolipoamide succinyltransferase. The molecular weight and
      estimated sequence length of the identified spots show that these fragments
      result from proteolytic activity in meat. Identification of the parent proteins
      and the enhanced post-mortem appearance of the degradation products make these
      specific peptides good candidates for meat quality markers, and further studies
      of these specific fragments will lead to a better understanding of the
      proteolytic activities involved in the post-mortem conversion of muscle to meat.

PMID- 12236672
TI  - Quantitative characterization of flavonoid compounds in Rooibos tea (Aspalathus
      linearis) by LC-UV/DAD.
AB  - Rooibos tea originates from the leaves and stems of the indigenous South African
      plant Aspalathus linearis. It has gained much attention for clinical purposes in
      the case of nervous tension, allergies (dermatitis), and various indigestive
      problems. Recently, antioxidative activity was also attributed to the tea on the
      basis of its flavonoid content. Therefore, an HPLC method using a C(18) reversed
      phase column was developed for the assay of 10 flavonoids in aqueous and
      methanolic infusions. Main compounds determined were the dihydrochalcone
      aspalthin, rutin, and orientin, and their content was in the range of 1.0 to 1.3
      mg/g. The identity of detected flavonoids was confirmed by comparing their
      retention times and UV and MS spectra with those of corresponding standards. In
      addition, the MS analysis showed evidence of the presence of other compounds such
      as nothofagin, dihydroisoorientin, and dihydroorientin.

PMID- 12236673
TI  - Detecting and quantifying sunflower oil adulteration in extra virgin olive oils
      from the eastern mediterranean by visible and near-infrared spectroscopy.
AB  - One hundred and thirty-eight oil samples have been analyzed by visible and near
      infrared transflectance spectroscopy. These comprised 46 pure extra virgin olive
      oils and the same oils adulterated with 1% (w/w) and 5% (w/w) sunflower oil. A
      number of multivariate mathematical approaches were investigated to detect and
      quantify the sunflower oil adulterant. These included hierarchical cluster
      analysis, soft independent modeling of class analogy (SIMCA method), and partial
      least squares regression (PLS). A number of wavelength ranges and data
      pretreatments were explored. The accuracy of these mathematical models was
      compared, and the most successful models were identified. Complete classification
      accuracy was achieved using 1st derivative spectral data in the 400-2498 nm
      range. Prediction of adulterant content was possible with a standard error equal
      to 0.8% using 1st derivative data between 1100 and 2498 nm. Spectral features and
      chemical literature were studied to isolate the structural basis for these
      models.

PMID- 12236674
TI  - Enzyme-linked immunosorbent assay for the pyrethroid deltamethrin.
AB  - A competitive enzyme-linked immunosorbent assay (ELISA) for the detection of
      deltamethrin was developed. Two haptens, cyano[3-(4-aminophenoxy)phenyl]methyl 1R
      cis-3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropanecarboxylate and 3-[(+/-)
      cyano[1R-cis-3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropan
      ecarbonyloxy]methyl]phenoxyacetic acid, were synthesized and conjugated with
      thyroglobulin as immunogens. Four antisera were generated and screened against
      six different coating antigens. The assay that was the most sensitive for
      deltamethrin was optimized and characterized. The I(50) for deltamethrin was 17.5
      +/- 3.6 microg/L, and the lower detection limit was 1.1 +/- 0.5 microg/L. This
      ELISA assay had relatively low cross-reactivities with other major pyrethroids,
      such as permethrin, phenothrin, bioresmethrin, cyfluthrin, and cypermethrin.
      Methanol was found to be the best organic cosolvent for this ELISA, with optimal
      sensitivity observed at a concentration of 40% (v/v). The assay parameters were
      unchanged at pH values between 5.0 and 8.0, whereas higher ionic strengths
      strongly suppressed the absorbances. To increase the sensitivity of the overall
      method, a C(18) sorbent-based solid-phase extraction was used for river water
      samples. River water samples fortified with deltamethrin were analyzed according
      to this method. Good recoveries and correlation with spike levels were observed.

PMID- 12236675
TI  - Constituents in evening primrose oil with radical scavenging, cyclooxygenase, and
      neutrophil elastase inhibitory activities.
AB  - Cold-pressed, non-raffinated evening primrose oil was found to contain lipophilic
      radical scavengers. A highly enriched fraction of these compounds could be
      obtained from the oil by extraction with aqueous ethanol and subsequent liquid
      liquid partitioning with petroleum. LC-DAD-MS analysis revealed that the fraction
      contained three aromatic compounds with identical UV and ESI-MS spectra. The
      compounds were isolated by RP-HPLC and their structures established by chemical
      and spectroscopic means as 3-O-trans-caffeoyl derivatives of betulinic, morolic,
      and oleanolic acid. The morolic acid derivative was a new compound. The three
      esters exhibited pronounced radical scavenging activity against the stable 2,2
      diphenyl-1-picrylhydrazyl radical and were potent inhibitors of neutrophil
      elastase and cyclooxygenase-1 and -2 in vitro. Commercial samples of evening
      primrose oils contained only traces of these lipophilic antioxidants.

PMID- 12236676
TI  - Novel oxidations of (+)-catechin by horseradish peroxidase and laccase.
AB  - Horseradish peroxidase (HRP; EC 1.11.1.7) catalyzed the H(2)O(2)-dependent
      oxidative coupling of (+)-catechin 1 to form three different biphenyl C-C dimers
      2-4, whereas Rhus vernicifera laccase catalyzed the formation of two new catechin
      hydroquinone adducts 5 and 6. Spectroscopic evidence showed that HRP dimers were
      linked through position 8 of the A-ring of one catechin moiety to C-5' of ring B
      in 2 and 4 and to C-2 of ring C in 3. The unusual catechin dicarboxylic acid
      dimer 4 was obtained by ortho cleavage of the E-ring. Hydroquinone served as both
      a shuttle oxidant and a reactant by coupling at C-2' and C-5' of the catechin B
      ring during laccase oxidations. HRP and laccase oxidation products were compared
      to D,L-alpha-tocopherol and (+)-catechin for their abilities to inhibit iron
      induced lipid peroxidation in rat brain homogenates and Fe(3+)-ADP/NADPH in rat
      liver microsomes, as measured by the intensity of thiobarbituric acid reactive
      substance. All metabolites exhibited anti-lipid peroxidation with IC(50) values
      approximately 2-8 times higher than those of standard compounds. Characteristic
      reaction products may prove to be novel markers for (+)-catechin antioxidant
      reactions in living systems.

PMID- 12236677
TI  - Modification of the rheological properties of whey protein isolate through the
      use of an immobilized microbial transglutaminase.
AB  - A process was developed in which calcium-independent, microbial transglutaminase
      (mTgase) was immobilized to controlled-pore glass. Avidin was adsorbed to glass
      beads that had been derivatized and biotinylated. The enzyme was biotinylated and
      adsorbed to the avidin affinity matrix. Solutions of 8% whey protein isolate
      (WPI) were then incubated with the mTgase beads, resulting in limited cross
      linking of whey proteins. As incubation time increased, intrinsic viscosity
      increased, gelation temperature decreased, and stronger, more brittle gels were
      formed upon heating. This process allowed for recycling of the enzyme, eliminated
      the requirement for a downstream inactivation step, and permitted control over
      the extent of cross-linking. The functional properties of several batches of WPI
      were modified using <10 mg of the same enzyme, illustrating the capacity of
      immobilized enzymes to be used more frequently in applications of this nature.

PMID- 12236678
TI  - Enzymatic synthesis of aroma compound xylosides using transfer reaction by
      Trichoderma longibrachiatum xylanase.
AB  - Enzymatic synthesis of aroma compound xylosides was performed by Trichoderma
      longibrachiatum xylanase. Information concerning the nature of xylosides present
      in the reaction medium was obtained by GC-EI-MS, by GC-NCI-MS of TFA derivatives,
      and by positive FAB-MS of the reaction mixtures. Moreover, the structures of
      isolated benzyl beta-D-xylopyranoside and 4-O-beta-xylopyranosyl-beta-D
      xylopyranoside were established by (1)H and (13)C NMR and heteronuclear two
      dimensional ((1)H-(13)C) chemical shift correlation. The results obtained for
      hexyl and benzyl alcohol xylosides indicated that a reaction implying a transfer
      of one to two or three xylose units from xylan was involved. The enzyme was able
      to recognize xylobiose, xylotriose, and xylan as xylose donors. Benzyl xyloside,
      produced independently of xylobioside and xylotrioside, was found as the major
      kinetic product of the reaction. Benzyl xyloside was produced in higher
      quantities and at a higher rate than that obtained for the di- and trixyloside
      derivatives. The maximum production for benzyl xyloside, 1.29 g/L, was obtained
      in the presence of hexane (50%) used as cosolvent. Xylosides and xylobiosides of
      several aroma compounds, (Z)-hex-3-en-1-ol, heptan-2-ol, geraniol, nerol, and
      citronellol, were synthesized in different amounts, from 850 mg/L for (Z)-hex-3
      en-1-yl xylosides to 1.5 mg/L for citronellyl xylosides. No synthesis occurred
      when menthol, linalool, and eugenol were used as acceptors.

PMID- 12236679
TI  - Lignin deposition and associated changes in anatomy, enzyme activity, gene
      expression, and ruminal degradability in stems of tall fescue at different
      developmental stages.
AB  - Stem tissues of tall fescue (Festuca arundinacea Schreb.) were sampled at three
      elongation stages and three reproductive stages. Anatomical analysis showed the
      deposition of guaiacyl (G) and syringyl (S) lignin during plant development and
      the formation of a lignified sclerenchyma ring. A dramatic increase in Klason
      lignin content was found from elongation stage to reproductive stage. Lignin
      composition analyzed by gas chromatography-mass spectrometry revealed that S
      lignin content and S/G ratio increased with stem development, but contents of p
      hydroxyphenyl (H) and G lignins decreased during the same period. S lignin
      content and S/G ratio also increased from the younger upper internode down to the
      older basal internode of the stem, but G and H lignin decreased in parallel.
      Relative O-methyltransferase activities increased during stem development and in
      parallel with the lignification process of stem. The pattern of enzyme activity
      during development varied with the choice of substrate, with highest activities
      seen when substrates were caffeoylaldehyde and 5-hydroxyferulic acid, and lowest
      activities were seen when caffeic acid and 5-hydroxyconiferyl alcohol were used
      as substrates. The expression of caffeic acid O-methyltransferase and cinnamyl
      alcohol dehydrogenase genes increased during the stem elongation stage and
      remained at high levels during the reproductive stages. The changes at
      anatomical, metabolic, and molecular levels during plant development were closely
      associated with lignification and degradability. This study provides an
      integrated picture of the molecular and chemical events that accompany changes in
      lignin deposition and ruminal degradability.

PMID- 12236680
TI  - Rate of degradation of alpha-tocopherol, squalene, phenolics, and polyunsaturated
      fatty acids in olive oil during different storage conditions.
AB  - Changes in the concentration of tocopherol, monophenols, o-diphenols, squalene,
      and polyunsaturated fatty acids in olive oil were evaluated during 1 year at
      various storage conditions. Samples of two different extra virgin olive oil
      (EOO), produced in Calabria (Italy), were stored in dark and in colorless
      bottles, filled up completely or to half, in order to simulate the domestic
      storage conditions. The extent of oxidation or photooxidation was monitored by
      periodic measurements of peroxide values and the rate of degradation of alpha
      tocopherol, o-diphenols, squalene, and polyunsaturated fatty acids. The
      quantitative analysis of the constituents has been performed by HPLC-DAD, HPLC
      MS, and GC-MS. The main changes in the concentrations of the analyzed compounds
      were associated with the major oxygen level in the half-empty glass bottles.
      alpha-Tocopherol was the first molecule to be oxidized (-20% after 2 months, -92%
      after 12 months). Squalene and o-diphenols were protected in the first months by
      the presence of alpha-tocopherol, and their content decreased significantly only
      after 6 and 8 months, respectively, in the half-empty bottles. The concentration
      of polyunsaturated fatty acids remained almost constant during 8 months for all
      four different storage conditions; their oxidation started when the level of the
      antioxidants decreased.

PMID- 12236681
TI  - Role of aldehydic derivatives in the condensation of phenolic compounds with
      emphasis on the sensorial properties of fruit-derived foods.
AB  - The reactions between (epi)catechin, mavidin 3-O-glucoside, and some aldehydes
      were investigated by LC/DAD and LC/ESI-MS analysis. The obtained results showed
      that the acetaldehyde-mediated condensation occurred more generally and glyoxylic
      acid, furfural, and 5-(hydroxymethyl)furfural (HMF) react in the same way in the
      first stages of the reactions. In terms of reactivity, reactions were faster with
      acetaldehyde than with glyoxylic acid, furfural, or HMF, where the reactions were
      slower. In the case of acetaldehyde, the obtained purple derivatives were more
      predominant and stable than the colorless adducts and no xanthylium salt was
      detected. Interactions involving glyoxylic acid yield purple adducts, which were
      obtained in small amount compared to the colorless ones. The latter were shown to
      proceed to more polymerized and yellowish derivatives. Finally, in the case of
      furfural and HMF, purple compounds involving flavanol and anthocyanin units were
      detected, and colorless compounds were shown to be predominant and to yield
      yellowish xanthylium salts.

PMID- 12236682
TI  - Interactions between cyanidin 3-O-glucoside and furfural derivatives and their
      impact on food color changes.
AB  - The reaction between (+)-catechin and cyanidin 3-O-glucoside was investigated in
      the presence of furfural and 5-(hydroxymethyl)furfural using LC/DAD and LC/MS
      analysis, and the obtained results were compared with those recorded with
      malvidin 3-O-glucoside. The appearance of colorless and red and yellow compounds
      was observed showing that the two polyphenols competed in the condensation
      process with a predominant formation of the reddish adducts. The colored
      compounds formed in the case of cyanidin 3-O-glucoside seemed to be more stable
      than those formed when the reaction was conducted with malvidin 3-O-glucoside.
      The detection of these reddish and yellowish compounds constitutes a new support
      for the contribution of this kind of reaction in the color evolution of fruit
      derived beverages. In addition, other unidentified compounds were also detected,
      showing the occurrence of other interaction pathways in addition to the
      polymerization process yielding oligomeric bridged derivatives and opening
      perspectives of further investigations of these model solutions.

PMID- 12236683
TI  - Foam aptitude of trepat and monastrell red varieties in cava elaboration. 1. Base
      wine characteristics.
AB  - The foam properties of base wines made from red autochthonous varieties (Trepat
      and Monastrell) were studied. Four wines of each variety were elaborated
      (fermented off skins at industrial scale in two consecutive harvests) and blended
      at different proportions with the white traditional variety (Macabeo, Xarel.lo,
      and Parellada) wines to elaborate Cava (closed-bottle-fermented sparkling wine).
      When crescent amounts of Trepat were added to the traditional white blend, the
      foamability and the color intensity (CI) of the wine increased polinomically. The
      increase of the CI depended on the year of harvest. Thus, oenologists could
      decide the blend proportion most suitable to elaborate either a "blanc de noirs"
      sparkling wine or a new type of Cava.

PMID- 12236684
TI  - Foam aptitude of trepat and monastrell red varieties in cava elaboration. 2.
      Second fermentation and aging.
AB  - The foam properties of sparkling wines (Cava) made from two red autochthonous
      grape varieties, Trepat and Monastrell, and coupages, including different
      percentages of them, were studied during second fermentation and aging. The
      effect of second fermentation on foam gave the highest decreases when the base
      wines had the highest foam values, while gave the lowest decreases or even
      increases for the base wines with the lowest foam characteristics. However, the
      greater the HM and Sigma of the base wine, the greater the foam values of the
      sparkling wine. Base wine determinations for quality control in cellars could
      provide information about future sparkling wine foaming. Acidity parameters,
      ethanol, sulfur, and polysaccharides contents were correlated to foam
      characteristics in the sparkling wines. In terms of color and foaming, wines made
      from the red varieties Trepat and Monastrell blended with white variety wines
      could be appropriate for elaborating "blanc de noirs" sparkling wines.

PMID- 12236685
TI  - Fermentability of grape must after inhibition with dimethyl dicarbonate (DMDC).
AB  - Dimethyl dicarbonate (DMDC) was added to grape must and to synthetic media and
      results showed that, at 20 degrees C, 150 mg.L(-)(1) DMDC completely inhibited
      the fermentation of a grape must that was previously inoculated with 10(6)
      cells.mL(-)(1) Saccharomyces bayanus and Saccharomyces uvarum. Brettanomyces
      intermedius, Candida guilliermondii, Hansenula jadinii, Hansenula petersonii,
      Kloeckera apiculata, Pichia membranaefaciens, and Saccharomyces cerevisiae were
      inhibited by 250 mg.L(-)(1). Candida valida was inhibited in the presence of 350
      mg.L(-)(1), whereas Hanseniaspora osmophila, Saccharomycodes ludwigii,
      Schizosaccharomyces pombe, and Zygosaccharomyces bailii required 400 mg.L(-)(1).
      Delay of fermentation (but not inhibition) was noted in the presence of 400 mg.L(
      )(1) for the following cultures: Brettanomyces anomalus, Hanseniaspora uvarum,
      Metschnikowia pulcherrima, Schizosaccharomyces japonicus, Torulaspora
      delbrueckii, and Zygosaccharomyces florentinus. Acetobacter aceti and
      Lactobacillus sp. were completely inhibited using 1000 and 500 mg.L(-)(1) DMDC,
      respectively. The fermentation of a grape must inoculated with 10(6) cells.mL(
      )(1) of different wine yeasts was delayed for 4 days after the prior addition of
      200 mg.L(-)(1) of DMDC; 200 mg.L(-)(1) DMDC did not show any residual inhibitory
      effect after 12 h, nor did 300 mg.L(-)(1) 24 h after the addition. In cellar
      experiments, indigenously contaminated grape musts (with and without skins)
      showed a delay in fermentation of 48 h after the addition of only 50 mg.L(-)(1)
      DMDC. The possibility of using DMDC (as pure grade as commercially available) in
      grape must as a disinfectant for the decontamination of musts indigenously
      contaminated with wild yeast should be considered seriously, despite its apparent
      low solubility in water.

PMID- 12236686
TI  - How low pH can intensify beta-damascenone and dimethyl trisulfide production
      through beer aging.
AB  - Flavor quality is of major importance to the consumer, but the flavor
      characteristics of beer appear to deteriorate greatly with time, at a rate
      depending on the composition of the beer and its storage conditions (notably pH).
      Prior to identifying the influence of pH on the development of the most intense
      staling flavors found in aged lager beers, the corresponding key flavor compounds
      were determined by aroma extract dilution analysis. In addition to trans-2
      nonenal, beta-damascenone seems at least as important in the flavor of aged beer.
      Ethyl butyrate, dimethyl trisulfide, 2-acetylpyrazine, 3
      (methylthio)propionaldehyde, 2-methoxypyrazine, maltol, gamma-nonalactone, and
      ethyl cinnamate are also relevant to the sensory profile of aged beer. Upon
      aging, a beer having a higher pH produces less beta-damascenone, because acid
      catalyzed glycoside hydrolysis is decreased. On the other hand, it produces more
      3-(methylthio)propionaldehyde, owing to Strecker degradation of methionine.
      Raising the beer pH additionally causes the release of 3
      (methylthio)propionaldehyde from sulfitic adducts. These adducts, more stable at
      a lower pH, protect the aldehyde against premature oxidation to 3
      (methylthio)propionic acid, thus making it available for dimethyl trisulfide
      formation during aging.

PMID- 12236687
TI  - QSAR evaluation of cyanohydrins' fumigation toxicity to house fly (Musca
      domestica) and lesser grain borer (Rhyzopertha dominica).
AB  - Using fumigation toxicity data of 11 natural and synthetic cyanohydrins to house
      fly (Musca domestica) and a stored-product pest, the lesser grain borer
      (Rhyzopertha dominica), the quantitative structure-activity relationships (QSAR)
      of cyanohydrins were examined by Oxford Molecular CAChe 3.2 and Microsoft Excel.
      This analysis used eight physicochemical parameters. Correlation between the
      LC(50) values for house fly and lesser grain borers was also evaluated. The
      results showed that log P, polarizability, and molar refractivity are the best
      descriptors to explain the relationship between the structure of cyanohydrins and
      biological effects in house flies, and to a lesser degree in lesser grain borers.
      A significant relationship was also found between the toxicity to house flies and
      lesser grain borers.

PMID- 12236688
TI  - Investigation of the tuber constituents of maca (Lepidium meyenii Walp.).
AB  - Lepidium meyenii, known in South America as maca, has received attention
      worldwide as a powerful energizer that improves physical and mental conditions
      and increases fertility. Because of these reports, we investigated the secondary
      metabolites of the tuber of maca. The methanol extract of the tuber of maca
      contained, in addition to free sugars and amino acids, the following: uridine,
      malic acid and its benzoyl derivative, and the glucosinolates, glucotropaeolin
      and m-methoxyglucotropaeolin. Because glucosinolates and their derived products
      have received increasing attention due to their biological activities, the
      occurrence of glucosinolate degradation products in the hexane extract was also
      investigated, and benzylisothiocyanate and its m-methoxy derivative were
      isolated. The two glucosinolates were semiquantified by HPLC, and
      benzylisothiocyanate was semiquantified by GC/MS. The methanol extract of maca
      tuber also contained (1R,3S)-1-methyltetrahydro-beta-carboline-3-carboxylic acid,
      a molecule which is reported to exert many activities on the central nervous
      system.

PMID- 12236689
TI  - Effects of moisture, temperature, and biological activity on the degradation of
      isoxaflutole in soil.
AB  - The effects of several environmental factors on the dissipation, transformation,
      and mineralization of isoxaflutole were investigated in laboratory incubations.
      In the soil, isoxaflutole hydrolyzed to a diketonitrile derivative, which is the
      active form of the herbicide. The diketonitrile was then metabolized to an
      inactive benzoic acid derivative and later into two unknown products, which were
      found only in small quantities. Degradation of isoxaflutole was faster in soil
      maintained at -100 or -1500 kPa compared to that in air-dry soil. At 25 degrees
      C, the half-lives for isoxaflutole were 9.6, 2.4, and 1.5 days in air-dry, -1500
      kPa, and -100 kPa moisture regimes, respectively. A simple Arrhenius expression
      described the response of isoxaflutole transformation (mineralization and
      transformation) to temperature in the range of 5 to 35 degrees C. An activation
      energy value (E(a)) of 67 kJ/mol for isoxaflutole suggested the transformation of
      the herbicide to the diketonitrile derivative was primarily a chemical reaction.
      Moreover, biological activity had little effect on the hydrolysis of
      isoxaflutole, with half-lives of 1.8 and 1.4 days in sterile and nonsterile soil,
      respectively. However, the transformation of diketonitrile to benzoic acid and
      the production of the unknown products were greatly reduced in the sterile soil,
      suggesting one or more biologically mediated processes.

PMID- 12236690
TI  - Degradation and sorption of pirimiphos-methyl in two Nigerian soils.
AB  - This research is a continuation of a study on the behavior of hydrophobic organic
      compounds in the environment and describes the simultaneous abiotic degradation
      and sorption of pirimiphos-methyl (O-2-diethylamino-6-methylpyrimidin-4-yl O,O
      dimethylphosphorothioate) under controlled conditions in soil/water slurries. A
      microfiltration-HPLC technique was employed to follow these processes in two well
      characterized soils from the Middle Belt region of Nigeria. Rapid sorption of the
      pesticide occurs during the first 10 min of equilibration and accounted for 37%
      of the original pirimiphos-methyl in the Rhodic Kandiustalf soil and for 41% of
      the original concentration in Aquic Ustropept soil. Subsequent slow processes
      were followed during the remaining 30 days of the experiment. During this time,
      first-order rate constants for disappearance from solution of pirimiphos-methyl
      were found to have values of 6.1 x 10(-)(7) and 9.8 x 10(-)(7) s(-)(1) for the
      Rhodic and Aquic soils, respectively. Similarly, rate constants for production of
      the product, pyrimidinol, were calculated to be 6.0 x 10(-)(7) and 9.4 x 10(-)(7)
      s(-)(1) for the Rhodic and Aquic soils, respectively, giving pesticide
      degradation half-lives of 13 and 8.5 days. Disappearance of the pesticide is
      discussed in terms of a scheme involving both sorptive uptake by the soil and
      degradation by hydrolysis in the presence of the soil matrix. The labile sorption
      capacities for pirimiphos-methyl in the Rhodic and Aquic soils were found to be
      0.75 and 0.90 micromol g(-)(1), respectively.

PMID- 12236691
TI  - Effect of cultivar and storage time on the volatile flavor components of baked
      potato.
AB  - Tubers of five cultivars of potato were stored at 4 degrees C for 2, 3, and 8
      months and baked in a conventional oven. The flavor compounds from the baked
      potato flesh were isolated by headspace adsorption onto Tenax and analyzed by gas
      chromatography-mass spectrometry. On a quantitative basis, compounds derived from
      lipid and Maillard reaction/sugar degradation dominated the flavor isolates, with
      sulfur compounds, methoxypyrazines, and terpenes making smaller contributions.
      Levels of 37 of the >150 detected compounds were monitored in each cultivar with
      time of storage. Many significant differences were found in levels of individual
      compounds, compound classes, and total monitored compounds for the individual
      effects of cultivar and storage time and for their two-way interaction.
      Differences may be explained by variations in levels of flavor precursors and
      activities of enzymes mediating flavor compound formation among cultivars and
      storage times. In addition, differences in agronomic conditions may partly
      account for variations among cultivars. Overall, of the compounds monitored,
      those most likely having the greatest flavor impact were 2-isopropyl-3
      methyoxypyrazine, 2-isobutyl-3-methoxypyrazine, dimethyl trisulfide, decanal, and
      3-methylbutanal, with methylpropanal, 2-methylbutanal, methional, and nonanal
      also being probable important contributors to flavor.

PMID- 12236692
TI  - Effect of different strains of Saccharomyces cerevisiae on production of
      volatiles in Napa Gamay wine and Petite Sirah wine.
AB  - Napa Gamay grapes were fermented with four different strains of the yeast
      Saccharomyces cerevisiae (VL1, MI16, Fermirouge, and RA17). Petite Sirah grapes
      were fermented with seven different strains of the same yeast (BM45, Fermirouge,
      RA17, NI, CX3079, A350, and A796). Volatile compounds formed in the wines were
      analyzed by gas chromatography/mass spectrometry. Volatile compounds found in
      both wines were alcohols, esters, and acids, as well as some miscellaneous
      compounds. Isoamyl alcohol was the compound found in the highest relative amount
      with all four yeast strains in the Napa Gamay wines, followed by 2-phenyl
      ethanol, monoethyl succinate, and hexanoic acid. The relative amounts of isoamyl
      alcohol ranged from 30.84% (VL1) to 43.28% (RA17). Major volatile compounds found
      in Petite Sirah wines were isoamyl alcohol, 2-phenyl ethanol, 2-hydroxy ethyl
      propanoate, monoethyl succinate, and octanoic acid. The several esters, including
      2-hydroxyethyl propanoate, may contribute to the fruity flavor of Petite Sirah
      wines. Overall, the S. cerevisiae yeast strains used to ferment Napa Gamay grapes
      and Petite Sirah grapes produced the same major components, with certain
      variations in formation levels.

PMID- 12236693
TI  - Synthesis and sensorial properties of mercaptoaldehydes.
AB  - Mercaptoalcohols and mercaptoketones have been described in the past decade as
      relevant character-impact compounds in various food products. On the other hand,
      very little is known of mercaptoaldehydes. Only 3-mercapto-2-methylpentanal and 3
      mercaptohexanal have been found in onions and beef liver, respectively. The aim
      of this work was to synthesize 13 mercaptoaldehydes not commercially available by
      combinatorial chemistry. Chromatographic analyses of the mixture allowed the
      determination of their retention indices and mass spectroscopy fragments for
      further identification in foods. Gas chromatography-olfactometry demonstrated how
      some of them are characterized by unusual odor and very low perception threshold.

PMID- 12236694
TI  - Identification of potent odorants in different green tea varieties using flavor
      dilution technique.
AB  - Two kinds of pan-fired green teas (Japanese Kamairi-cha and Chinese Longing tea)
      were compared with the common Japanese green tea (Sen-cha). Application of the
      aroma extract dilution analysis (AEDA) using the volatile fraction of the Sen
      cha, Kamairi-cha and Longing tea infusions revealed 32, 51, and 52 odor-active
      peaks with flavor dilution factors between 16 and 1024, respectively. (Z)-1,5
      Octadien-3-one (metallic, geranium-like), 4-mercapto-4-methyl-2-pentanone (meaty,
      black currant-like), methional (potato-like), (E,Z)-2,6-nonadienal (cucumber
      like), and 3-methylnonane-2,4-dione (green, fruity, hay-like) showed high flavor
      dilution factors in all varieties. In addition, 2-acetyl-1-pyrroline (popcorn
      like), 2-ethyl-3,5-dimethylpyrazine (nutty), 2,3-diethyl-5-methylpyrazine
      (nutty), and 2-acetyl-2-thiazoline (popcorn-like) belonged to the most potent
      odorants only in the pan-fired green teas. Among these odorants, 2-acetyl-1
      pyrroline and 2-acetyl-2-thiazoline were identified for the first time among the
      tea volatiles.

PMID- 12236695
TI  - Spinach (Spinacia oleracea) powder as a natural food-grade antioxidant in deep
      fat-fried products.
AB  - The addition of spinach (Spinacia oleracea) powder in flour dough as a natural
      antioxidant was investigated, and oxidation of frying oil and the lipid in fried
      products during frying was also studied. Flour dough with spinach powder was
      rolled into sheets of 0.1 cm thickness and then cut into squares to be fried.
      Each frying was performed in 160 degrees C soybean oil for 1 min, repeated every
      20 min for 20 h. Fried samples were analyzed immediately or after being stored at
      60 degrees C for 12 days under dark. The lipid content of fried dough was lower
      in samples with the addition of spinach powder. Spinach in the dough decreased
      accumulation of the polar compounds in soybean oil during frying but had little
      effect on the fried dough. It also reduced conjugated diene and aldehyde
      formation in the lipid of fried dough during storage. Improvement in lipid
      oxidative stability, presumably due to pigments in spinach, was more noticeable
      in the fried products during storage than in the frying oil.

PMID- 12236696
TI  - Jojoba seed meal proteins associated with proteolytic and protease inhibitory
      activities.
AB  - The jojoba, Simmondsia chinensis, is a characteristic desert plant native to the
      Sonoran desert. The jojoba meal after oil extraction is rich in protein. The
      major jojoba proteins were albumins (79%) and globulins (21%), which have similar
      amino acid compositions and also showed a labile thrombin-inhibitory activity.
      SDS-PAGE showed two major proteins at 50 kDa and 25 kDa both in the albumins and
      in the globulins. The 25 kDa protein has trypsin- and chymotrypsin-inhibitory
      activities. In vitro digestibility of the globulins and albumins resembled that
      of casein and soybean protein concentrates and was increased after heat
      treatment. The increased digestibility achieved by boiling may be attributed to
      inactivation of the protease inhibitors and denaturation of proteins.

PMID- 12236697
TI  - Purification and characterization of a thermostable alpha-galactosidase from
      Thermoanaerobacterium polysaccharolyticum.
AB  - Food ingredients containing alpha-1,6-galactoside bonds elicit gastrointestinal
      disturbances in monogastric animals, including humans. Pretreatment of such
      ingredients with alpha-galactosidase (EC 3.2.1.22) has the potential to alleviate
      this condition. For this purpose, a thermostable alpha-galactosidase from
      Thermoanaerobacterium polysaccharolyticum was purified by a combination of anion
      exchange and size exclusion chromatographies. The enzyme has a monomeric
      molecular weight of approximately 80 kDa; however, it is active as a dimer. The
      optimum temperature for enzyme activity is 77.5 degrees C. Approximately 84 and
      88% of enzyme activity remained after 36.5 h of incubation at 70 and 65 degrees
      C, respectively. Optimum activity was observed at pH 8.0, with a broad range of
      activity from pH 5.0 to 9.0. Different transition metals had weak to strong
      inhibitory effects on enzyme activity. The K(m) and V(max) of the enzyme are 0.29
      0.345 mM and 200-232 micromol/min/mg of protein, respectively. Importantly,
      enzyme activity was only slightly inhibited by 75-100 mM galactose, an end
      product of hydrolysis. Enzyme activity was specific for the alpha-1,6-galactosyl
      bond, and activity was demonstrated on melibiose and soy molasses.

PMID- 12236698
TI  - Isolation of a galactomannan that enhances macrophage activation from the edible
      fungus Morchella esculenta.
AB  - The edible mushroom Morchella esculenta is among the most highly prized and
      morphologically recognizable fungi in the world. We describe the isolation from a
      polar extract of M. esculenta carpophores of a high-molecular-weight
      galactomannan, about 1.0 million Da, that exhibits immunostimulatory activity. At
      3.0 microg/mL the galactomannan polysaccharide increased NF-kappa B directed
      luciferase expression in THP-1 human monocytic cells to levels 50% of those
      achieved by maximal activating concentration (10 microg/mL) of
      lipopolysaccharide. This galactomannan comprises about 2.0% of the dry fungal
      material weight, and its glycosyl components include mannose (62.9%) and
      galactose (20.0%).

PMID- 12236699
TI  - Chemical composition of shallot (Allium ascalonicum Hort.).
AB  - An extensive phytochemical analysis of the polar extracts from bulbs of shallot,
      Allium ascalonicum Hort., led to the isolation of two new furostanol saponins,
      named ascalonicoside A1/A2 (1a/1b) and ascalonicoside B (4), respectively, along
      with compounds 2a and 2b, most likely extraction artifacts. On the basis of 2D
      NMR and mass spectrometry data, the structures of the novel compounds were
      elucidated as furost-5(6)-en-3beta,22alpha-diol 1beta-O-beta-D-galactopyranosyl
      26-O-[alpha-L-rhamnopyranosyl-(1-->2)-O-beta-D-glucopyranoside] (1a), its epimer
      at position 22 (1b), and furost-5(6),20(22)-dien-3beta-ol 1beta-O-beta-D
      galactopyranosyl 26-O-[alpha-L-rhamnopyranosyl-(1-->2)-O-beta-D-glucopyranoside]
      (4). This is the first report of furostanol saponins in A. ascalonicum. High
      concentrations of quercetin, isorhamnetin, and their glycosides were also
      isolated and described.

PMID- 12236700
TI  - Varietal differences among the polyphenol profiles of seven table grape cultivars
      studied by LC-DAD-MS-MS.
AB  - Polyphenols present in red table grape varieties Red Globe, Flame Seedless,
      Crimson Seedless, and Napoleon, and the white varieties Superior Seedless,
      Dominga, and Moscatel Italica were analyzed by HPLC-DAD-MS. The anthocyanins
      peonidin 3-glucoside, cyanidin 3-glucoside (and their corresponding p-coumaroyl
      derivatives), malvidin 3-glucoside, petunidin 3-glucoside, and delphinidin 3
      glucoside were found. In addition, caffeoyltartaric acid, p-coumaroyltartaric
      acid, and the flavonols quercetin 3-glucuronide, quercetin 3-rutinoside,
      quercetin 3-glucoside, kaempferol 3-galactoside, kaempferol 3-glucoside, and
      isorhamnetin 3-glucoside were detected. Flavan-3-ols were also detected, and were
      identified as gallocatechin, procyanidin B1, procyanidin B2, procyanidin B4,
      procyanidin C1, catechin, and epigallocatechin. These phenolics were present only
      in the skin, as the flesh of these grape cultivars was almost devoid of these
      compounds. Anthocyanins were the main phenolics in red grapes ranging from 69
      (Crimson Seedless) to 151 (Flame Seedless) mg/kg fresh weight of grapes, whereas
      flavan-3-ols were the most abundant phenolics in the white varieties ranging from
      52 (Dominga) to 81 (Moscatel Italica) mg/kg fresh weight of grapes. Total
      phenolics ranged from 115 (Dominga) to 361 (Flame Seedless) mg/kg fresh weight of
      grapes. This means that a serving of unpeeled table grapes (200 g) could provide
      up to 72 mg of total phenolics (Flame Seedless). These results indicate that the
      intake of unpeeled table grapes should be recommended in dietary habits as a
      potential source of antioxidant and anticarcinogenic phenolic compounds.

PMID- 12236701
TI  - Analysis of glycated and ascorbylated proteins by gas chromatography-mass
      spectrometry.
AB  - Proteins or poly-L-lysine which were incubated in the presence of ascorbic acid,
      dehydroascorbic acid (ascorbylation), or various sugars (glycation) were analyzed
      by gas chromatography-mass spectrometry (GC-MS). To also detect more labile
      reaction products, the Maillard modified proteins or poly-L-lysine were
      enzymatically hydrolyzed and reacted with N-methyl-N-(tert
      butyldimethylsilyl)trifluoroacetamide to form the N(O)-tert-butyldimethylsilyl
      (tBDMS) derivatives prior to GC analysis. Under these conditions, the known
      Maillard products N (epsilon)-(carboxymethyl)lysine (1), oxalic acid mono-N
      (epsilon)-lysinylamide (2), and N (epsilon)-(carboxyethyl)lysine (3) could be
      simultaneously detected and quantified in glycated and ascorbylated proteins.
      Additionally, N (epsilon)-(1-carboxy-3-hydroxypropyl)-L-lysine (4) was identified
      for the first time as a Maillard product of proteins. Under the conditions
      applied here, 4 was found only in ascorbylated proteins or poly-L-lysine, but not
      in glycated proteins. Maillard-modified poly-L-lysine was further subjected to
      high-performance liquid chromatography (HPLC) analysis after enzymatic hydrolysis
      and formation of the phenyl isothiocyanate derivatized amino acids. Using this
      method, N (epsilon)-formyl-L-lysine (5), which cannot be distinguished from 2 by
      GC-MS analysis, was identified for the first time as a glycation product.
      Compound 5 is mainly formed from ribose, lactose, and fructose. The indicated
      Maillard products were quantified in beta-lactoglobulin (GC-MS) or poly-L-lysine
      (HPLC) which were glycated or ascorbylated using different precursors.

PMID- 12236702
TI  - Ability of surfactant micelles to alter the physical location and reactivity of
      iron in oil-in-water emulsion.
AB  - The purpose of this research was to determine how surfactant micelles influence
      iron partitioning and iron-promoted lipid oxidation in oil-in-water emulsions.
      Lipids containing ferric ions were used to produce oil-in-water emulsions, and
      continuous-phase iron concentrations in emulsions were measured as a function of
      varying continuous-phase polyoxyethylene 10-lauryl ether (Brij) concentrations.
      Continuous-phase iron concentrations increased with increasing surfactant micelle
      concentrations (0.1-2.0%) and storage time (1-7 days). At pH 3.0, the
      concentration of continuous-phase iron was higher than at pH 7.0. Similar trends
      in iron solubilization by Brij micelles were observed when either hexadecane or
      corn oil was used as the lipid phase. Lipid oxidation rates, as determined by the
      formation of lipid hydroperoxides and headspace hexanal, in corn oil-in-water
      emulsions containing iron decreased with increasing surfactant concentrations
      (0.5-2.0%). These results indicate that surfactant micelles could alter the
      physical location and prooxidant activity of iron in oil-in-water emulsions.

PMID- 12236703
TI  - Characterization of carotenoid high-producing Capsicum annuum cultivars selected
      for paprika production.
AB  - Twelve selected pepper (Capsicum annuum L.) cultivars, bred for mechanical
      harvesting (grouped ripeness) and adaptation to different cultivation cycles
      (short to long), have been characterized by their carotenoid pigment content and
      composition with the aim of producing high-quality paprika. A detailed analysis
      of the carotenogenesis was performed throughout the ripening process, but with
      special emphasis on the ripe stage, with the aim of selecting the best cultivar
      for paprika production. The MA1 cultivar (with grouped ripeness and very short
      cultivation cycle) showed the highest carotenoid content (12697.58 mg/kg dwt),
      followed by DN5 and RN2 cultivars with 11086.88 and 10393.29 mg/kg dwt,
      respectively. Most of the cultivars (MA3, RN1, LR2, LR7, DN3, DR6, Datler, and
      Mulato) showed a total carotenoid content in the range of 7000-9700 mg/kg dwt. In
      general, chlorophyll-retaining character was related to high carotenoid content
      (cultivars DN3, DN5, MA3, Mulato, RN1, and RN2). The general trend of the
      cultivation cycle was that the shorter the cycle, the higher the total carotenoid
      content (as exemplified by the cultivar MA1). The lowest total carotenoid content
      was found for the RR1 cultivar (4856.77 mg/kg dwt), which showed the longest
      cultivation cycle. Carotenogenic capacity of the cultivars has been discussed
      relative to total carotenoid content and the R/Y and Caps/Zeax ratios, the main
      quality traits for breeding cultivars for production of high-quality paprika. The
      cultivar MA1, with the highest total carotenoid content, high R/Y (2.11) ratio,
      and highest Caps/Zeax (9.85) ratio, was found to be the most suitable cultivar
      for paprika production in terms of carotenoid pigment biosynthesis capacity.
      Moreover, this cultivar has a short cultivation cycle and grouped ripeness, which
      are both important characteristics for a proper application of mechanical
      harvesting. The potential improvement of other varieties is also discussed.

PMID- 12236704
TI  - Isoflavone-free soy protein prepared by column chromatography reduces plasma
      cholesterol in rats.
AB  - To know whether isoflavones are responsible for the hypocholesterolemic effect of
      soy protein, the effect on plasma cholesterol of isoflavone-free soy protein
      prepared by column chromatography was examined in rats. Five-week-old male
      Sprague-Dawley rats were fed cholesterol-enriched AIN-93G diets containing either
      20% casein (CAS), 20% soy protein isolate (SPI), 20% isoflavone-free SPI (IF
      SPI), 19.7% IF-SPI + 0.3% isoflavone-rich fraction (isoflavone concentrate, IC),
      or 20% CAS + 0.3% IC for 2 weeks. Plasma total cholesterol concentrations of rats
      fed SPI and IF-SPI were comparable and were significantly lower than that of rats
      fed CAS. The addition of IC to the CAS and IF-SPI did not influence plasma
      cholesterol level. Fecal steroid excretion of the three SPI groups was higher
      than that of the two CAS groups, whereas the addition of IC showed no effect.
      Thus, a significant fraction of the cholesterol-lowering effect of SPI in rats
      can be attributed to the protein content, but the isoflavones and other minor
      constituents may also play a role.

PMID- 12236705
TI  - Characterization of selenium species in Brazil nuts by HPLC-ICP-MS and ES-MS.
AB  - Brazil nuts have been classified as the foodstuffs that contain the highest level
      of unadulterated selenium, an essential trace element that appears to prevent
      cancer. To date, characterization of the selenium species in brazil nuts has not
      yet been investigated. In this work, various sample preparation approaches,
      including microwave extractions and enzymatic treatments, are examined with the
      goal of species preservation and subsequent selenium speciation; of these
      approaches, an enzymatic treatment with Proteinase K proved most effective. High
      performance liquid chromatography (HPLC) separation strategies and inductively
      coupled plasma mass spectrometry (ICP-MS) detection schemes will also be
      presented. Extracts are evaluated against available standards for the
      commercially obtainable seleno-amino acids, selenomethionine (SeMet),
      selenoethionine (SeEt), and selenocystine (SeCys); selenomethionine was
      demonstrated to be the most abundant of these seleno-amino acids. Further
      characterization of unidentified selenium-containing peaks is attempted by the
      employment of several procedures, including electrospray-mass spectrometry (ES
      MS). A peptide structure was identified; however, this was considered a tentative
      proposal due to the large background produced by the extremely complicated brazil
      nut matrix.

PMID- 12236706
TI  - Antiallergic tea catechin, (-)-epigallocatechin-3-O-(3-O-methyl)-gallate,
      suppresses FcepsilonRI expression in human basophilic KU812 cells.
AB  - We previously found that the O-methylated derivative of (-)-epigallocatechin-3-O
      gallate (EGCg), (-)-epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG' '3Me), has
      potent antiallergic activity. The high-affinity IgE receptor, FcepsilonRI, is
      found at high levels on basophils and mast cells and plays a key role in a series
      of acute and chronic human allergic reactions. To understand the mechanism of
      action for the antiallergic EGCG' '3Me, the effect of EGCG' '3Me on the cell
      surface expression of FcepsilonRI in human basophilic KU812 cells was examined.
      Flow cytometric analysis showed that EGCG' '3Me was able to decrease the cell
      surface expression of FcepsilonRI. Moreover, immunoblot analysis revealed that
      total cellular expression of the FcepsilonRI alpha chain decreased upon treatment
      with EGCG' '3Me. FcepsilonRI is a tetrameric structure comprising one alpha
      chain, one beta chain, and two gamma chains. The level of mRNA production of each
      subunit in KU812 cells was investigated. EGCG' '3Me reduced FcepsilonRI alpha and
      gamma mRNA levels. The cross-linkage of FcepsilonRI causes the activation of
      basophils, which leads to the secretion of inflammatory mediators including
      histamine. EGCG' '3Me treatment inhibited the FcepsilonRI cross-linking-induced
      histamine release. These results suggested that EGCG' '3Me can negatively
      regulate basophil activation through the suppression of FcepsilonRI expression.

PMID- 12236707
TI  - Absorption of phenolic acids in humans after coffee consumption.
AB  - Despite extensive literature describing the biological effects of polyphenols,
      little is known about their absorption from diet, one major unresolved point
      consisting of the absorption of the bound forms of polyphenols. In this view, in
      the present work we studied the absorption in humans of phenolic acids from
      coffee, a common beverage particularly rich in bound phenolic acids, such as
      caffeic acid, ferulic acid, and p-coumaric acid. Coffee brew was analyzed for
      free and total (free + bound) phenolic acids. Chlorogenic acid (5'-caffeoylquinic
      acid), a bound form of caffeic acid, was present in coffee at high levels, while
      free phenolic acids were undetectable. After alkaline hydrolysis, which released
      bound phenolic acids, ferulic acid, p-coumaric acid, and high levels of caffeic
      acid were detected. Plasma samples were collected before and 1 and 2 h after
      coffee administration and analyzed for free and total phenolic acid content. Two
      different procedures were applied to release bound phenolic acids in plasma: beta
      glucuronidase treatment and alkaline hydrolysis. Coffee administration resulted
      in increased total plasma caffeic acid concentration, with an absorption peak at
      1 h. Caffeic acid was the only phenolic acid found in plasma samples after coffee
      administration, while chlorogenic acid was undetectable. Most of caffeic acid was
      present in plasma in bound form, mainly in the glucuronate/sulfate forms. Due to
      the absence of free caffeic acid in coffee, plasma caffeic acid is likely to be
      derived from hydrolysis of chlorogenic acid in the gastrointestinal tract.

PMID- 12236708
TI  - Use of a rat model to evaluate tall fescue seed infected with introduced strains
      of Neotyphodium coenophialum.
AB  - Experimental cultivars of the pasture grass tall fescue are infected with unique
      strains of the fungal endophyte Neotyphodium coenophialum, which produce low
      concentrations of ergot alkaloids. A rat model was evaluated as a tool for rapid,
      initial screening of experimental cultivars considered to be nontoxic. Rats were
      fed diets that included seed from experimental cultivars of tall fescue with
      introduced strains of N. coenophialum and a toxic control diet containing seed of
      the cultivar Kentucky 31 (KY31), with its endemic strain of N. coenophialum. Rats
      were preconditioned to a nontoxic diet and then fed treatment diets for 13 days
      with 5 days at thermoneutrality (21 degrees C) followed by 8 days under heat
      stress (31 degrees C). For most of the 13-day treatment period, rats fed KY31
      exhibited depressed daily intake compared to those fed diets of cultivars with
      introduced endophytes (P < 0.05). In addition, rats fed KY31 exhibited
      significantly less weight than rats on other diets after heat treatment was
      imposed. For all initial trials and repeated trials, total intake and total gain
      calculated at the end of each trial were the most consistent indicators of
      toxicity.

PMID- 12236709
TI  - 2-alkylcyclobutanones as irradiation dose indicators in irradiated ground beef
      patties.
AB  - Alkylcyclobutanones have been recognized as chemical markers of irradiated lipid
      containing foods since 1970. They are important because they are produced solely
      as a result of irradiation and not any other processing method. This study
      investigated the formation of 2-dodecylcyclobutanone (2-DCB) and 2-tetradec-5'
      enylcyclobutanone (2-TDCB) in irradiated ground beef patties from commercial and
      noncommercial sources. Patties were irradiated using a (60)C source (gamma
      irradiation) and electron beam irradiation, at five targeted absorbed doses of
      0.5, 1.0, 2.5, 5.0, and 7.0 kGy. Commercially available irradiated patties were
      also studied. A supercritical fluid extraction (SFE) procedure was optimized and
      used for the extraction and isolation of the alkylcyclobutanones. Samples can be
      used for extraction without a prior cleanup step, which makes this procedure
      rapid and convenient to use. Identification and quantitation of the
      cyclobutanones were done by gas chromatography-mass spectroscopy. 2-DCB was
      detected in all of the irradiated samples (including commercial patties), and its
      concentration increased linearly with the irradiation dose. Electron beam
      irradiation produced a greater amount of 2-DCB compared to gamma-irradiation at
      dose levels >2.5 kGy. 2-TDCB was detected only at the two higher irradiation
      doses, whereas both marker compounds were not detected in the non-irradiated
      samples.

PMID- 12236710
TI  - Blue myoglobin reconstituted with an iron porphycene shows extremely high oxygen
      affinity.
AB  - Myoglobin will be a good scaffold for engineering a function into proteins. To
      modulate the physiological function of myoglobin, almost all approaches have been
      demonstrated by site-directed mutagenesis, however, there are few studies which
      show a significant improvement in the function. In contrast, we focused on the
      replacement of heme in the protein with an artificial prosthetic group. Recently,
      we prepared a novel myoglobin reconstituted with an iron porphycene as a
      structural isomer of mesoheme. The bluish colored reconstituted myoglobin is
      relatively stable and the deoxymyoglobin reversibly binds ligands. Interestingly,
      the O2 affinity of the reconstituted myoglobin, 1.1 x 109 M-1, is a significant
      1,400-fold higher than that of the native myoglobin. Furthermore, the unfavorable
      autoxidation kinetics show 7-fold decrease in rate for the reconstituted
      myoglobin relative to the native myoglobin, indicating the stable oxy-form
      against autoxidation. The net results come from the slow dissociation of the O2
      ligand in the reconstituted myoglobin, koff = 0.11 s-1, because of the formation
      of strong hydrogen bond between His64 and negatively charged dioxygen. The
      present study indicates that the replacement of native heme with an artificially
      created prosthetic group will give us a unique function into a hemoprotein.

PMID- 12236711
TI  - Anion-anion assembly: a new class of anionic supramolecular polymer containing
      3,4-dichloro-2,5-diamido-substituted pyrrole anion dimers.
AB  - Two molecules containing two 2,5-diamido,3,4-dichloropyrrole units linked via 1,3
      or 1,4-substituted benzene rings have been synthesized. The pyrrole groups in
      these compounds deprotonate in the presence of tetrabutylammonium fluoride and
      form pyrrole anion dimers via NH...N- hydrogen bonds. This dimerization process
      results in the formation of polyanionic chains linked via an unusual "orthogonal"
      hydrogen-bonding array.

PMID- 12236712
TI  - Implications of active site constraints on varied DNA polymerase selectivity.
AB  - DNA polymerase selectivity often varies significantly depending on the DNA
      polymerase. The origin of this varying error propensity is elusive. It is assumed
      that DNA polymerases form nucleotide binding pockets that differ in properties
      such as shape and tightness. We tested this prediction and studied HIV-1 RT by
      employment of size-augmented nucleotides and site-directed mutagenesis of the
      enzyme. New valuable insights into the mechanism of DNA polymerase fidelity were
      obtained. The presented study provides experimental evidence that variations of
      steric constraints within the nucleotide binding pocket of at least two DNA
      polymerases cause variations in nucleotide incorporation selectivity. Thus, our
      results support the concept of active site tightness as a causative in
      differential fidelity among DNA polymerases.

PMID- 12236713
TI  - 15N,(1)H Heteronuclear correlation NMR of gramicidin A in DMPC-d(67).
AB  - We have studied gramicidin A, an environmentally sensitive polymorphic
      pentadecapeptide, fully 15N-labelled and dispersed in a highly deuterated
      phospholipid bilayer system. By submitting the sample to fast magic angle
      spinning, we were able to reduce the polypeptide amide hydrogen linewidths to 160
      Hz, and hence to partially resolve them. By correlating these resonances with the
      40 Hz wide dipolar coupled 15N in a 2D-CROPSY (cross-polarization spectroscopy)
      experiment, it was possible to observe the 20 partially overlapping 1H-15N signal
      pairs from the polypeptide backbone and sidechains. Both chemical shift
      distributions closely match those of the same peptide in SDS micelles, but only
      poorly match those of conformationally different gramicidin A in
      trifluoroethanol, dimethylsulfoxide, or methanol/chloroform mixture. Our results
      are indicative of the N-to-N right-handed beta6.3-helix conformation of
      gramicidin A and offer sufficient resolution to encourage development of
      experiments to measure orientational or distance restraints using through-space
      dipolar couplings.

PMID- 12236715
TI  - A new experimental protocol for intrazeolite photooxidations. The first product
      based estimate of an upper limit for the intrazeolite singlet oxygen lifetime.
AB  - The intrazeolite photooxidations of several alkenes have been examined in hexane
      and in perfluorohexane slurries. The ability of perfluorohexane to increase the
      affinity of alkenes for the interior of the zeolite was documented. The nearly
      identical reaction rates in the two slurry solvents are attributed to a leveling
      of the singlet oxygen lifetime by the zeolite framework. A consideration of the
      rates of the various intrazeolite processes was used to estimate an upper limit
      for the intrazeolite lifetime of singlet oxygen.

PMID- 12236714
TI  - Reductive activation of dioxygen by a myoglobin reconstituted with a flavohemin.
AB  - We successfully converted myoglobin, an oxygen-storage hemoprotein, into an
      oxygen-activating hemoprotein like cytochrome P450s by replacing the native hemin
      with the artificially created flavohemin. The reconstituted myoglobin, rMb(1),
      was chacterized by ESI-TOF-mass, UV-vis, and fluorescence spectra. The 1H NMR
      spectrum of cyanomet rMb(1) indicates that two hemin conformers are present in a
      ratio of 1:1. Upon the addition of NADH to the buffer solution of rMb(1) in the
      presence of SOD and catalase, the oxymyoglobin was rapidly formed. As compared
      with the formation of the oxygenated native myoglobin in the presence of 10-N
      (acetylaminoethyl)isoalloxazine, the rate constant of the oxyheme formation in
      rMb(1) is 6 times larger. This is because the flavin covalently linked to the
      terminal heme propionate functions as an effective mediator of an electron
      transfer from NADH to the hemin in rMb(1). Furthermore, rMb(1) shows the
      deformylation activity, when 2-phenylpropionaldehyde (2-PPA) was employed as a
      substrate. This result indicates that the oxyheme is reductively activated to
      Fe(III)-peroxoanion (Fe(III)-O22-). The result in this report is the first
      example of the activation of dioxygen by myoglobin. This study shows the utility
      of the replacement of the native hemin with a chemically modified one for the
      functionalization of myoglobin.

PMID- 12236716
TI  - Oxidative group transfer to Co(I) affords a terminal Co(III) imido complex.
AB  - The synthesis of the first terminal imido complex of cobalt, [PhBP3]CoN-p-tolyl,
      is reported. Its synthesis proceeds by oxidative group transfer from cobalt(I)
      upon addition of tolyl azide at room temperature. This species and a related eta1
      diazoalkane adduct have been structurally characterized. The diamagnetic imido
      complex [PhBP3]CoN-p-tolyl reacts with CO to liberate isocyanate and the
      cobalt(I) dicarbonyl complex [PhBP3]Co(CO)2.

PMID- 12236717
TI  - Direct generation of nucleophilic chiral palladium enolate from 1,3-dicarbonyl
      compounds: catalytic enantioselective Michael reaction with enones.
AB  - Generation of chiral palladium enolates from 1,3-dicarbonyl compounds with the
      palladium aqua complex and its application to the highly efficient catalytic
      enantioselective Michael reaction with enones are described. The palladium aqua
      complexes are likely to supply Bronsted base and Bronsted acid successively
      during the reaction. The former activates the carbonyl compounds to give chiral
      palladium enolates, and the latter cooperatively activates enones. Using a
      catalytic amount (2-10 mol %) of the palladium complexes, the various 1,3
      dicarbonyl compounds including diketones and beta-ketoesters were converted to
      the desired Michael adducts in good yields (69-92%) with excellent enantiomeric
      excesses (89-99% ee).

PMID- 12236718
TI  - Entrapping enzyme in a functionalized nanoporous support.
AB  - The enzyme organophosphorus hydrolase (OPH) was spontaneously entrapped in
      carboxylethyl- or aminopropyl-functionalized mesoporous silica with rigid,
      uniform open-pore geometry (30 nm). This approach yielded larger amounts of
      protein loading and much higher specific activity of the enzyme when compared to
      the unfunctionalized mesoporous silica and normal porous silica with the same
      pore size. When OPH was incubated with the functionalized mesoporous silica,
      protein molecules were sequestered in or excluded from the porous material,
      depending on electrostatic interaction with the charged functional groups. OPH
      entrapped in the organically functionalized nanopores showed an exceptional high
      immobilization efficiency of more than 200% and enhanced stability far exceeding
      that of the free enzyme in solution. The combination of high protein loading,
      high immobilization efficiency and stability is attributed to the large and
      uniform pore structure, and to the optimum environment introduced by the
      functional groups.

PMID- 12236719
TI  - Single-crystalline star-shaped nanocrystals and their evolution: programming the
      geometry of nano-building blocks.
AB  - We demonstrate a novel synthetic scheme that can be used to differentially guide
      the shape of PbS semiconductor nanocrystals. Our study first demonstrates the
      discovery of single-crystalline star-shaped nanocrystals as novel transient
      species. We then carefully probe their shape evolution toward other novel
      nanostructures (e.g., tadpole-, L-, T-, cross-shapes, highly faceted star shapes,
      truncated octahedrons and cubes, etc.) and systematically elucidate the key
      parameters that control these final structures. In principle, through programming
      these growth parameters, the desired architecture of building blocks of other
      kinds of nano materials can be constructed.

PMID- 12236720
TI  - Allenes as carbon nucleophiles in palladium-catalyzed reactions: observation of
      anti attack of allenes on (pi-allyl)palladium complexes.
AB  - In the palladium-catalyzed cyclization of allenic allylic esters using Pd(dba)2
      as catalyst, it was shown that the allene acts as a carbon nucleophile.
      Intermediates were isolated and stereochemical studies established that the
      double bond of the allene has attacked the (pi-allyl)palladium intermediate on
      the face opposite to that of palladium.

PMID- 12236721
TI  - Thermal desorption behavior and binding properties of DNA bases and nucleosides
      on gold.
AB  - A comparison of the binding of DNA bases (adenine, cytosine, guanine, and
      thymine) and nucleosides (2'deoxyadenosine, 2'deoxycytidine, 2'deoxyguanosine,
      and thymidine) to gold thin films is presented. Desorption of
      monolayer/submonolayer and multilayer films of the adsorbates on gold studied via
      temperature-programmed desorption (TPD) and reflection-absorption infrared (RAIR)
      spectroscopy reveals that there are major differences in the binding affinities
      of the different bases to gold, for example, thymine DeltaHdes = 111 +/- 2 kJ/mol
      compared to guanine DeltaHdes = 146 +/- 2 kJ/mol. The differences can be
      rationalized by molecular structures of the bases and their binding modes to gold
      surfaces deduced from IR data. Similar trends in desorption energies, shifted to
      lower desorption energy by more than 10 kJ/mol, are observed for deoxynucleoside
      layers on gold thin films.

PMID- 12236722
TI  - Development of a decarboxylative palladation reaction and its use in a Heck-type
      olefination of arene carboxylates.
AB  - The development of a palladium-catalyzed decarboxylative coupling reaction of
      arene carboxylates with olefinic substrates is described. The optimized procedure
      for decarboxylative palladation employs Pd(O2CCF3)2 as catalyst (0.2 equiv) in
      the presence of Ag2CO3 (3 equiv) in the solvent 5% DMSO-DMF and proceeds at
      temperatures of 80-120 degrees C with a wide range of arene carboxylates and
      alkenes as substrates. The process is proposed to proceed by an initial Ar-SE
      reaction involving ipso attack of an electrophilic Pd(II) intermediate on an
      arene carboxylate to form an arylpalladium(II) species with loss of carbon
      dioxide. This intermediate is then proposed to react with an olefinic substrate
      by steps common to the Heck coupling process. Reoxidation of the liberated Pd(0)
      in situ is proposed to establish the catalytic cycle.

PMID- 12236723
TI  - Increased antioxidant reactivity of vitamin C at low pH in model membranes.
AB  - The reactivity of the water-soluble antioxidant vitamin C (l-ascorbic acid)
      depends on pH. It is generally recognized that the ascorbate monoanion, which
      predominates at neutral physiological pH, acts as a stronger antioxidant than the
      protonated form, ascorbic acid. Fluorazophore-L, a long-lived fluorescent probe,
      was employed as a mimic for lipid peroxyl radicals. The experiments with micellar
      and bilayer membrane models demonstrate that vitamin C becomes, in fact, a more
      powerful antioxidant at low pH. This phenomenon may be general for the
      interception of reactive oxidizing species at the lipid/water interface.

PMID- 12236724
TI  - An ion conductor that recognizes osmotically-stressed phospholipid bilayers.
AB  - A synthetic ion conductor (1), derived from cholic acid and spermine, has been
      found capable of recognizing osmotic stress in liposomes made from 1,2
      dipalmitoleoyl-sn-glycero-3-phosphocholine [(C16:1)PC]. Thus, when large
      unilamellar vesicles of (C16:1)PC are placed under hypotonic conditions, the
      Na+/Li+ transport activity of 1 increases by as much as 1 order of magnitude,
      relative to isotonic conditions

PMID- 12236725
TI  - Three-dimensionally ordered mesoporous niobium oxide.
AB  - Three-dimensionally ordered mesoporous niobium oxide was prepared by a neutral
      templating route with the addition of a trace amount of cations, which have 5-
      and 2-nm pore diameter and wall thickness, respectively.

PMID- 12236726
TI  - All-atom structure prediction and folding simulations of a stable protein.
AB  - We present results from all-atom, fully unrestrained ab initio folding
      simulations for a stable protein with nontrivial secondary structure elements and
      a hydrophobic core. The construct, "trpcage", is a 20-residue sequence optimized
      by the Andersen group at University of Washington and is currently the smallest
      protein that displays two-state folding properties. Compared over the well
      defined regions of the experimental structure, our prediction has a remarkably
      low 0.97 A Calpha root-mean-square-deviation (rmsd) and 1.4 A for all heavy
      atoms. The simulated structure family displays additional features that are
      suggested by experimental data, yet are not evident in the family of NMR-derived
      structures.

PMID- 12236727
TI  - Evidence for the HOOO(-) anion in the ozonation of 1,3-dioxolanes: hemiortho
      esters as the primary products.
AB  - Low-temperature ozonation (-78 degrees C) of 2-methyl-1,3-dioxolane (1a) in
      acetone-d6, methyl acetate, and tert-butyl methyl ether produced both the
      corresponding acetal hydrotrioxide (3a, ROOOH) and the hemiortho ester (2a, ROH)
      in molar ratio 1:5. Both intermediates were fully characterized by 1H, 13C, and
      17O NMR spectroscopy, and they both decomposed to the corresponding hydroxy ester
      at higher temperatures. The mechanism involving the HOOO- anion formed by the
      abstraction of the hydride ion by ozone to form an ion pair, R+ -OOOH, with its
      subsequent collapse to either the corresponding hemiortho ester (ROH) or the
      acetal hydrotrioxide (ROOOH) was proposed. This mechanism is supported by the
      PISA/B3LYP/6-311++G(3df,3pd) calculations.

PMID- 12236728
TI  - Catalytic CO oxidation by a gold nanoparticle: a density functional study.
AB  - Gold is usually considered very noble. It does not oxidize, and the surface of
      gold cannot adsorb most molecules from the gas phase. Yet it has been found that
      nanometer size gold particles on different oxide supports can act as catalysts
      even at or below room temperature. We present self-consistent density functional
      calculations showing that even an isolated Au10 cluster should be able to
      catalyze the CO oxidation reaction even below room temperature. We use the
      calculations to analyze the origin of this effect and suggest that the
      extraordinary reactivity can be traced back to special reaction geometries
      available at small particles in combination with an enhanced ability of low
      coordinated gold atoms to interact with molecules from the surroundings.

PMID- 12236729
TI  - Intramolecular and intermolecular N-H...C(5)H(5)(-) hydrogen bonding in
      magnesocene adducts of alkylamines. Implications for chemical vapor deposition
      using cyclopentadienyl source compounds.
AB  - Magnesocene adducts of alkylamines were prepared and characterized. Treatment of
      3-amino-2,4-dimethylpentane, isopropylamine, tert-butylamine, benzylamine, or N
      isopropylbenzylamine with magnesocene at ambient temperature in toluene afforded
      the amine adducts Cp2Mg(NH2CH(CH(CH3)2)2) (91%), Cp2Mg(NH2iPr) (80%),
      Cp2Mg(NH2tBu) (67%), Cp2Mg(NH2CH2Ph) (80%), and Cp2Mg(NH(CH(CH3)2)(CH2C6H5))
      (91%). These adducts are stable at ambient temperature, and
      Cp2Mg(NH2CH(CH(CH3)2)2) can be sublimed at 60 degrees C/0.05 Torr without any
      evidence for reversion to magnesocene. The solid-state structure of
      Cp2Mg(NH2CH(CH(CH3)2)2) contains eta5- and eta2-cyclopentadienyl ligands, and the
      hydrogen atoms on the coordinated amine nitrogen atom participate in
      intramolecular and intermolecular hydrogen bonding to the eta2-cyclopentadienyl
      ligand. The observed hydrogen bonding is relevant to the path by which
      cyclopentadiene is eliminated from metal cyclopentadienyl CVD source compounds
      during film growth employing acidic element hydrides as co-reactants.

PMID- 12236730
TI  - Isolation and structure of [HC[CH(SiMe(3))(SnMe(3))](2)](+): a remarkably stable
      sec-alkyl cation.
AB  - The reaction of the tin-substituted propene Me3Sn(R)CHCH=CHR (R = SiMe3) with
      MCl4 in dichloromethane in the presence of Me3SnCl gives the first examples of
      isolable sec-alkyl carbocation salts, [HC{CH(R)SnMe3}2]+M2Cl9- (M = Zr, Hf). The
      compounds are thermally stable and, unlike previously isolated trialkyl
      carbocations, do not require superacidic media or weakly coordinating anions for
      stability. The crystal structure and DFT calculations suggest polarization of the
      Sn substituents and hyperconjugation as the reason for the unexpected stability.
      The stabilizing effect of tin is significantly stronger than that of Si. The
      carbocations are effective initiators for the polymerization of isobutene,
      isoprene, and alpha-methylstyrene.

PMID- 12236731
TI  - Contact resistance in metal-molecule-metal junctions based on aliphatic SAMs:
      effects of surface linker and metal work function.
AB  - Using conducting probe atomic force microscopy (CP-AFM), we have formed molecular
      tunnel junctions consisting of alkanethiols and alkane isonitrile self-assembled
      monolayers sandwiched between gold, platinum, silver, and palladium contacts. We
      have measured the resistance of these junctions at low bias (dV/dI |V=0) as a
      function of alkane chain length. Extrapolation to zero chain length gives the
      contact resistance, R0 . R0 is strongly dependent on the type of metal used for
      the contacts and decreases with increasing metal work function; that is, R0,Ag >
      R0,Au > R0,Pd > R0,Pt. R0 is approximately 10% smaller for Au junctions with
      isonitrile versus thiol surface linkers. We conclude that the Fermi level of the
      junction lies much closer to the HOMO than to the LUMO.

PMID- 12236732
TI  - An anchoring role for FeS clusters: chelation of the amino acid moiety of S
      adenosylmethionine to the unique iron site of the [4Fe-4S] cluster of pyruvate
      formate-lyase activating enzyme.
AB  - Pyruvate formate-lyase activating enzyme (PFL-AE) generates the catalytically
      essential glycyl radical on pyruvate formate-lyase via the interaction of the
      catalytically active [4Fe-4S]+ cluster with S-adenosylmethionine (AdoMet). Like
      other members of the Fe-S/AdoMet family of enzymes, PFL-AE is thought to function
      via generation of an AdoMet-derived 5'-deoxyadenosyl radical intermediate;
      however, the mechanistic steps by which this radical is generated remain to be
      elucidated. While all of the members of the Fe-S/AdoMet family of enzymes appear
      to have a unique iron site in the [4Fe-4S] cluster, based on the presence of a
      conserved three-cysteine cluster binding motif, the role of this unique site has
      been elusive. Here we utilize 35-GHz pulsed electron nuclear double resonance
      (ENDOR) studies of the [4Fe-4S]+ cluster of PFL-AE in complex with isotopically
      labeled AdoMet (denoted [1+/AdoMet]) to show that the unique iron serves to
      anchor the AdoMet for catalysis. AdoMet labeled with 17O at the carboxylate shows
      a coupling of A = 12.2 MHz, consistent with direct coordination of the
      carboxylate to the unique iron of the cluster. This is supported by 13C-ENDOR
      with the carboxylato carbon labeled with 13C, which shows a hyperfine coupling of
      0.71 MHz. AdoMet enriched with 15N at the amino position gives rise to a spectrum
      with A(15N) = 5.8 MHz, consistent with direct coordination of the amino group to
      a unique iron of the cluster. Together, the results demonstrate that the unique
      iron of the [4Fe-4S] cluster anchors AdoMet by forming a classical N/O chelate
      with the amino and carboxylato groups of the methionine fragment.

PMID- 12236733
TI  - Utilization of alternate substrates by the first three modules of the epothilone
      synthetase assembly line.
AB  - The epothilones, a family of macrolactone natural products produced by the
      myxobacterial species Sorangium cellulosum, are of current clinical interest as
      antitumor agents. Inspection of the structure of the epothilones suggests a
      hybrid polyketide/nonribosomal peptide biosynthetic origin, and the recent
      sequencing of the epothilone biosynthetic gene cluster has validated this
      proposal. Here we have examined unnatural substrates with the first two enzymes
      of the biosynthetic pathway, EpoA and EpoB, to investigate the enzymatic
      construction of alternate heterocyclic structures and the subsequent elongation
      of these products by the third enzyme of the pathway, EpoC. The epothilone
      biosynthetic machinery can utilize serine to install an oxazole in place of a
      thiazole in the epothilone structure and will tolerate functionalized donor
      groups from the EpoA-ACP domain to produce epothilone fragments modified at the
      C21 position. These studies with the early enzymes of the epothilone biosynthesis
      cluster suggest that combinatorial biosynthesis may be a viable means for
      producing a variety of epothilone analogues that incorporate diversity into the
      heterocycle starter unit.

PMID- 12236734
TI  - Synthesis, structure, and ferromagnetic behavior of decacopper(II) cluster
      complex supported by hexaanionic p-tert-butylthiacalix[6]arene.
AB  - A nanosized decacopper(II) cluster complex was synthesized using p-tert
      butylthiacalix[6]arene as a ligand. In the complex, the calixarene assumes a
      "pinched cone" conformation and acts as an undecadentate ligand via six phenoxy
      oxygen and five sulfur atoms. The resulting pentacopper(II) subunits are
      connected by two hydroxo and two oxo groups to form decacappoer(II) cluster core.
      The core structure remains intact in alcoholic solution as shown by ESI MS. The
      temperature dependence of chimT clearly shows ferromagnetic behavior of the core
      due to orthogonality between two adjoining magnetic orbitals of copper(II) ions.

PMID- 12236735
TI  - The active site of arsenite oxidase from Alcaligenes faecalis.
AB  - Arsenite oxidase, a member of the DMSO reductase family of molybdenum enzymes,
      has two molecules of guanosine dinucleotide molybdenum cofactor coordinating the
      molybdenum at the active site. X-ray absorption spectroscopy indicates that the
      Mo-S bonds shorten from 2.47 to 2.37 A upon reduction with the physiological
      substrate. It also indicates the presence of an oxo ligand at 1.70 A in both
      oxidized and reduced forms of the enzyme, together with a short, 1.83 A, Mo-O
      bond in the oxidized form that is lost upon reduction. Resonance Raman
      spectroscopy indicates that the two pterin dithiolene moieties have different
      aromaticities, with one, the Q-pterin, having a more discrete dithiolate
      structure while the other, the P-pterin, has considerable pi-delocalization. Our
      results indicate that the structure of arsenite oxidase is intermediate between
      that seen in other molybdenum enzymes, in which one ligand to the metal is
      provided by the polypeptide (serine, cysteine, or selenocysteine), and tungsten
      enzymes that lack a peptide ligand.

PMID- 12236736
TI  - A warning on the use of radical traps as a test for radical mechanisms: they
      react with palladium hydrido complexes.
AB  - Typical radical traps (galvinoxyl, TEMPO, DPPH) react with palladium hydrides,
      sometimes at rates competitive with those of palladium hydride catalyzed
      reactions that follow an insertion mechanism (for example, alkene isomerization).
      Thus, positive results for radical reaction tests can be misleading. The
      complexes with more polarizable (neutral complexes rather than cationic) and more
      accessible hydrides, and the less sterically protected radical traps, react
      faster.

PMID- 12236737
TI  - Dynamics of electron injection in DNA hairpins.
AB  - The dynamics of electron injection has been investigated in DNA hairpins
      possessing a stilbenediether electron donor linker by means of femtosecond
      transient absorption spectroscopy. Ultrafast electron injection and charge
      recombination are observed with neighboring cytosine or thymine bases; however,
      guanine-guanine base pairs are not reduced, permitting the investigation of the
      distance dependence of charge injection.

PMID- 12236738
TI  - Remarkable stability and enhanced optical activity of a chiral supramolecular bis
      porphyrin tweezer in both solution and solid state.
AB  - Interaction of the achiral syn (face-to-face) conformer of the ethane-bridged
      bis(zinc octaethylporphyrin) with the enantiopure 1,2-diaminocyclohexane results
      in the exclusive formation of a supramolecular chiral tweezer. This 1:1 host
      guest complex exhibits remarkable stability in both solution (even upon
      photoexcitation) and solid-state phases, with a high degree of optical activity
      arising from the two-point interaction mode and optimal spatial geometry.

PMID- 12236739
TI  - Structure sensitivity and photocatalytic reactions of semiconductors. Effect of
      the last layer atomic arrangement.
AB  - Photocatalytic reactions of heterogeneous systems, probably the most complex
      catalytic reactions, are central to a wide variety of phenomena including those
      of evolution theory, energy conversion, and environmental cleanup. Although
      catalytic reactions are essentially surface driven, the effect of bulk structure
      is particularly important for the photo processes in solid materials because it
      directly affects the excitation and charge transfer mechanisms. To treat surface
      photocatalytic reactions, it is necessary to differentiate between surface and
      bulk effects. We have successfully decoupled the surface-bulk effects by using a
      TiO2 (001) single crystal. This was achieved by allowing for surface
      reconstruction and measuring the rate of reaction for the two thermodynamically
      stable reconstructed surfaces of the oxide single crystal in ultrahigh vacuum
      conditions. A considerable difference, in the quantum yield of the photoreaction
      of acetic acid, between the two reconstructed surfaces was found. This large
      difference (due to different surface electron-hole recombination rates) between
      both reconstructed surfaces could not be seen without decoupling the surface from
      bulk effects.

PMID- 12236740
TI  - Long-range oxidative damage to DNA: protection of guanines by a nonspecifically
      bound disulfide.
AB  - One-electron oxidation of DNA generates a base radical cation ("hole") that
      migrates through the duplex and causes damage at guanines. Unrepaired damage may
      lead to mutations. It has been suggested that "sacrificial guanines" in intron
      regions of DNA might serve to protect genes from damage. We have investigated the
      ability of a noncovalently bound sacrificial reagent to protect DNA from damage.
      Irradiation of an anthraquinone (AQ)-linked DNA duplex injects a radical cation
      into the DNA that causes reactions at GG steps close to and farther from the AQ.
      Bis[2-(3-(aminopropyl)amino)ethyl]disulfide, an analogue of spermine, binds to
      duplex DNA. Irradiation of the AQ-linked DNA in the presence of this disulfide
      suppresses the reaction at both GG steps and protects the DNA from damage. It is
      suggested that evolutionary pressure for the preservation of genomic integrity
      would yield disulfide-containing compounds optimized to bind to DNA and
      neutralize base radical cations.

PMID- 12236741
TI  - Magnetic structure of the europium fulleride ferromagnet Eu(6)C(60).
AB  - The powder neutron diffraction technique has been used for the direct observation
      of magnetic scattering below a Curie temperature of approximately 14 K in the
      fullerene-based molecular ferromagnet Eu6C60. Europium is in the divalent state
      with a magnetic moment of 7.1(3) muB per atom, and the configurational symmetry
      of the magnetic structure is body-centered cubic. Close contacts between Eu2+ and
      neighboring C60 units provide the signature of orbital hybridization, which can
      evidently account for the conducting and magnetic properties of the material.

PMID- 12236742
TI  - Total synthesis of (+)-alpha-onocerin in four steps via four-component coupling
      and tetracyclization steps.
AB  - A remarkably short (four steps, 31% overall yield) enantioselective synthesis of
      the structurally unique C2-symmetric tetracyclic triterpene (+)-alpha-onocerin
      (1) has been developed. The brevity of this mechanism depends on the assembly of
      four fragments (two molecules of a chiral epoxy ketone and two molecules of
      vinyllithium) to generate the chiral bis-epoxide 4 in one step, and on the
      efficient formation of all four carbocyclic rings in one step by cation-olefin
      tetracyclization. New and general methodology for the conversion of vinyl tert
      butyldimethylsilyl ethers to vinyl triflates with retention of E or Z olefinic
      geometry also was utilized in the synthesis of 1. A short enantioselective
      synthesis of a non-C2-symmetric diastereomer of 1 is also described which uses
      the new methodology.

PMID- 12236743
TI  - Intramolecular Diels-Alder and tandem intramolecular Diels-Alder/1,3-dipolar
      cycloaddition reactions of 1,3,4-oxadiazoles.
AB  - The scope of intramolecular Diels-Alder and a novel tandem Diels-Alder/1,3
      dipolar cycloaddition cascade of 1,3,4-oxadiazoles is disclosed. In the cases
      examined, the tandem cycloadditions construct three new rings with formation of
      four new C-C bonds and set all six stereocenters about a central six-membered
      ring in a single step including three contiguous and four total quaternary
      centers without a trace of a second diastereomer.

PMID- 12236744
TI  - Environmental effects on phosphoryl group bonding probed by vibrational
      spectroscopy: implications for understanding phosphoryl transfer and enzymatic
      catalysis.
AB  - We have used vibrational spectroscopy to study bonding in monosubstituted
      dianionic phosphates, both to learn more about basic properties intrinsic to this
      important class of biological substrates and to assess the ability of vibrational
      spectroscopy to provide a "sensor" or probe of the local environment experienced
      by the phosphoryl group. We examined the bonding properties of the phosphoryl
      group via vibrational spectroscopy for a series of compounds in which the
      phosphoryl substituent was varied systematically and extensively. A broad linear
      correlation of the bridging P-O(R) bond length and the pK(a) of the substituent
      alcohol was observed. The results indicate that the P-O(R) bond changes by only
      approximately 0.04 A with alcohol substituents that vary in pK(a) by
      approximately 12 units, suggesting that phosphoryl group bonding responds in a
      subtle but regular manner to changes in the local environment. We also determined
      the effect on the phosphoryl bonding from changes in the solvent environment.
      Addition of dimethyl sulfoxide (DMSO) elongates the bridging bond, presumably as
      a result of lessened solvation to the nonbridging oxygens and conservation of
      bond order to phosphorus. Finally, we have addressed the relationship between
      ground-state bonding properties and reactivity, as changing the leaving group
      substituent and adding DMSO have large rate effects, and it was previously
      proposed that lengthening of the bond to be broken is the cause of the increased
      reactivity. The results herein suggest, however, that the change in the bridging
      bond energy is small compared to the changes in energy that accompany the
      observed reactivity differences. Further analysis indicates that electrostatic
      interactions can provide a common driving force underlying both bond lengthening
      and the observed rate increases. We suggest that ground-state distortions of
      substrates bound to enzymes can provide a readout of the electrostatic active
      site environment, an environment that is otherwise difficult to assess.

PMID- 12236745
TI  - Proximity effects in monolayer films: kinetic analysis of amide bond formation at
      the air-water interface using (1)H NMR spectroscopy.
AB  - The kinetics of amide bond formation in a monolayer film has been studied by
      proton NMR spectroscopy. Compression of a hexadecyl thioester of N-acetyl glycine
      (1) and a hexadecyl amide of glycine (2) at the air-water interface produces a
      single dipeptide product (4) that remains at the surface once formed. Extraction
      of the reaction mixture from the interface, followed by (1)H NMR spectroscopy,
      provides quantitative data on the rate of product formation. The kinetics of this
      reaction was examined as a function of surface pressure, subphase pH, and
      temperature. The monolayer provides an effective molarity for the reaction of
      approximately 500 M as compared to the bimolecular reaction of 1 and 4 in
      chloroform solution. The first-order rate constant for the reaction of 1 and 2 in
      the monolayer is less than 70-fold slower than k(cat) for condensation of the
      first amide bond in the enzymatic synthesis of the cyclic antibiotic gramicidin S
      by gramicidin S synthetase. Activation energies of the reaction were extracted
      from the temperature dependence of the rate constants of the reaction and are 9.9
      +/- 1.0 and 2.1 +/- 0.2 kcal/mol for the chloroform solution and monolayer
      reactions, respectively. The pK(a) of 2 in the monolayer was estimated to be
      approximately 0.5 pK(a) units lower than that of related amines in solution. The
      lower pK(a) at the interface as compared to that in solution may be ascribed to
      increased electrostatic repulsion at the interface relative to solution. The rate
      of reaction in the monolayer was also followed by monitoring changes in surface
      area as a function of time. The rate constant for the reaction of 1 and 4 as
      determined by changes in surface area differs significantly from the rate
      determined by NMR. The results indicate that measurements of surface area versus
      time may yield erroneous rate constants for reactions in monolayers.

PMID- 12236746
TI  - Solution and solid-state models of peptide CH...O hydrogen bonds.
AB  - Fumaramide derivatives were analyzed in solution by (1)H NMR spectroscopy and in
      the solid state by X-ray crystallography in order to characterize the formation
      of CH...O interactions under each condition and to thereby serve as models for
      these interactions in peptide and protein structure. Solutions of fumaramides at
      10 mM in CDCl(3) were titrated with DMSO-d(6), resulting in chemical shifts that
      moved downfield for the CH groups thought to participate in CH...O=S(CD(3))(2)
      hydrogen bonds concurrent with NH...O=S(CD(3))(2) hydrogen bonding. In this
      model, nonparticipating CH groups under the same conditions showed no significant
      change in chemical shifts between 0.0 and 1.0 M DMSO-d(6) and then moved upfield
      at higher DMSO-d(6) concentrations. At concentrations above 1.0 M DMSO-d(6), the
      directed CH...O=S(CD(3))(2) hydrogen bonds provide protection from random DMSO
      d(6) contact and prevent the chemical shifts for participating CH groups from
      moving upfield beyond the original value observed in CDCl(3). X-ray crystal
      structures identified CH...O=C hydrogen bonds alongside intermolecular NH...O=C
      hydrogen bonding, a result that supports the solution (1)H NMR spectroscopy
      results. The solution and solid-state data therefore both provide evidence for
      the presence of CH...O hydrogen bonds formed concurrent with NH...O hydrogen
      bonding in these structures. The CH...O=C hydrogen bonds in the X-ray crystal
      structures are similar to those described for antiparallel beta-sheet structure
      observed in protein X-ray crystal structures.

PMID- 12236747
TI  - Secondary structure of DNA is recognized by slightly cross-linked cationic
      hydrogel.
AB  - Interaction of salmon sperm DNA (300-500 bp) and ultrahigh molecular mass DNA
      (166 kbp) from bacteriophage T4dC with linear poly(N-diallyl-N-dimethylammonium
      chloride) (PDADMAC) and slightly cross-linked (#) PDADMAC (#PDADMAC) hydrogel in
      water has been studied by means of UV-spectroscopy, ultracentrifugation, atomic
      force, and fluorescence microscopy (FM). It is found that the linear polycation
      induced compaction of either native (double-stranded) or denatured (single
      stranded) DNA by forming PDADMAC-DNA interpolyelectrolyte complexes (IPEC)s. At
      the same time, #PDADMAC hydrogel is able to distinguish between native and
      denatured DNA. Native DNA is adsorbed and captured in the hydrogel surface layer,
      while denatured DNA diffuses to the hydrogel interior until the whole hydrogel
      sample is transformed into the cross-linked IPEC. Both native and denatured DNA
      can be completely released from the hydrogel in appropriate conditions with no
      degradation by adding a low molecular salt. The data observed using conventional
      physicochemical methods with respect to DNA of a moderate molecular mass
      remarkably correlate with the pictures directly observed for ultrahigh molecular
      mass DNA in dynamics by using FM.

PMID- 12236748
TI  - Kinetics and mechanism for CO(2) scrambling in a N-carboxyimidazolidone analogue
      for N(1)-carboxybiotin.
AB  - The N-carboxyimidazolidone anion, 2(-), was prepared as an analogue for N(1)
      carboxybiotin, and the kinetics of its CO(2)-dependent chemistry were studied in
      polar aprotic media. The objective was to assess the viability of unimolecular
      CO(2) elimination from N(1)-carboxybiotin as a microscopic step in biotin
      dependent carboxyl transfer enzymes. The anionic 2(-) was prepared as its lithium
      salt by first deprotonating 2-imidazolidone with phenyllithium, followed by
      direct reaction with carbon dioxide. This procedure also permitted isolation of
      the (13)C enriched derivative 2(-)[(13)C] by reaction with (13)CO(2). Proton and
      (13)C NMR and isotope-dependent FTIR measurements confirmed that carboxylation
      had occurred at the nitrogen atom of 2-imidazolidone to give 2(-). Time-dependent
      FTIR spectroscopy showed that Li2 undergoes carboxyl exchange with free carbon
      dioxide, with kinetics indicative of rate-limiting unimolecular dissociation of
      the N-CO(2) bond. Under these conditions, the weak Lewis acid Mg(2+) catalyses
      the exchange of 2(-) with free CO(2), which appears to be related to the ability
      of the metal ion to coordinate to 2(-). Reaction of Li2 with carboxylic acids in
      DMSO results in acid-dependent decarboxylation of 2(-) with a rate that is
      dependent on the concentration of the acid and its pK(a). A common mechanistic
      framework is presented for both Lewis acid catalyzed carboxyl exchange and acid
      dependent decarboxylation that involves initial interaction at the carbonyl
      oxygen and which has the effect of polarizing the nitrogen lone pair toward the
      imidazolidone ring rather than the carboxyl group. Lewis acid interaction with
      the carbonyl oxygen thus weakens the N-CO(2)(-) bond and functions as a trigger
      for dissociation of CO(2). In the context of biotin-dependent enzymes, this
      suggests a means by which the kinetically stable N(1)-carboxybiotin cofactor
      intermediate might be triggered for dissociation of CO(2).

PMID- 12236750
TI  - Quenching of n,pi*-excited states in the gas phase: variations in absolute
      reactivity and selectivity.
AB  - The quenching of the n,pi*-excited azoalkane 2,3-diazabicyclo[2.2.2]oct-2-ene by
      19 heteroatom-containing electron and hydrogen donors, that is, amines, sulfides,
      ethers, and alcohols, was investigated in the gas phase. Deuterium isotope
      effects were measured for 9 selectively deuterated derivatives. The data support
      the involvement of an excited charge-transfer complex, that is, an exciplex, for
      tertiary amines and sulfides, and a competitive direct hydrogen transfer from the
      C-H bonds of ethers or from the N-H or O-H bonds of secondary and primary amines
      or alcohols. The recently observed "inverted" solvent effect for the fluorescence
      quenching of azoalkanes by amines and sulfides in solution is supported by the
      observed rate constants in the gas phase, which are substantially larger than
      those in solution. A more pronounced inverted solvent effect for the weaker
      electron-donating sulfides and a presumably faster exciplex deactivation result
      in a switch-over in absolute reactivity relative to tertiary amines in the gas
      phase. Most importantly, the kinetic data demonstrate that the reactivity of the
      strongly dipolar O-H and N-H bonds in photoinduced hydrogen abstraction reactions
      shows a larger decrease upon solvation than that of the less polar C-H bonds. The
      azoalkane data are compared with previous studies on quenching of n,pi*-triplet
      excited ketones in the gas phase.

PMID- 12236749
TI  - Development of the [3 + 2] annulations of cyclohexenylsilanes and chlorosulfonyl
      isocyanate: application to the total synthesis of (+/-)-peduncularine.
AB  - The synthesis of (+/-)-peduncularine was accomplished using the [3 + 2]
      annulation of an allylic silane with chlorosulfonyl isocyanate to assemble the
      bicyclic core of the alkaloid. The stereochemistry of the annulation product was
      employed to control the installation of the indolylmethyl side chain at C-7 with
      complete stereoselectivity.

PMID- 12236751
TI  - Structure and stereodynamics of N,N-bis(silyloxy)enamines.
AB  - The structure and stereodynamics of N,N-bis(silyloxy)enamines (1), a new class of
      enamines with extraordinary reactivity, have been simulated by the DFT PBE/TZP
      method. The computed pattern of dynamic behavior and structural peculiarities of
      1 was shown to reflect adequately the results of the studies by a series of
      physical methods including X-ray analysis and dynamic NMR and UV spectroscopies,
      which provided evidence of a rather low barrier for rotation around the C,N
      single bond, a negligible contribution of the n-pi-conjugation, a high barrier of
      inversion, and high pyramidality of the nitrogen atom.

PMID- 12236752
TI  - Enantioselective synthesis of the protein phosphatase inhibitor (-)-motuporin.
AB  - A highly convergent asymmetric synthesis of the protein phosphatase inhibitor
      motuporin 1a is described. Synthesis and coupling of the individual peptide
      fragments [34 + 35 --> 51] followed by macrocyclization afforded the fully
      protected motuporin precursor 33, which is converted to the natural product by
      dehydration and ester hydrolysis. Six of the eight stereogenic centers associated
      with the natural product were introduced using asymmetric crotylsilane bond
      construction methodology. Our approach features an efficient Pd(0)-catalyzed
      cross-coupling reaction between a configurationally well-defined vinyl zinc
      intermediate 22 and an (E)-vinyl iodide 7, which afforded compound 43, resulting
      in the construction of the trisubstituted (E,E)-diene system of the motuporin
      side chain. Improved reaction conditions for macrocyclization in the formation of
      33 are also detailed.

PMID- 12236753
TI  - Efficient chemoselective carboxylation of aromatics to arylcarboxylic acids with
      a superelectrophilically activated carbon dioxide-Al(2)Cl(6)/Al system.
AB  - Aromatic carboxylic acids are obtained in good to excellent yield essentially
      free of diaryl ketones by carboxylation of aromatics with a carbon dioxide
      Al(2)Cl(6)/Al system at moderate temperatures (20-80 degrees C). To optimize
      reaction conditions and study the reaction mechanism, experimental variables
      including temperature, amount of Al(2)Cl(6)/Al, various Lewis acids, role of
      metal additive, carbon dioxide pressure, etc. were studied. The carboxylation
      reaction was found to be stoichiometric rather than catalytic, with aluminum
      chloride forming a dichloroaluminate of carboxylic acids. Although the
      carboxylation takes place using AlCl(3) itself, the presence of metal additives,
      especially Al, increased the yield and selectivity of carboxylic acids. Because
      it was not possible to distinguish between two possible mechanistic pathways of
      the reaction on the basis of the experimental results, theoretical calculations
      using density functional theory (DFT) were also carried out. One possible pathway
      involves an initial complex between benzene and Al(2)Cl(6), with subsequent
      formation of organoaluminum intermediates (PhAlCl(2) and PhAl(2)Cl(5)). The other
      proceeds through the formation of various complexes of CO(2) with aluminum
      chloride (AlCl(3))(n), n = 1-4. The calculations have shown that the
      organometallic pathway, leading eventually through the formation of
      phenylaluminum dichloride, is endothermic by 33 kcal/mol. In contrast, the
      preferred CO(2)-AlCl(3) complex forms in an exothermic reaction (-6.0 kcal/mol)
      as does CO(2)AlCl(2)(+). On the basis of both experimental and calculational
      findings, the most feasible reaction mechanism proposed involves
      superelectrophilic aluminum chloride activated carbon dioxide reacting with the
      aromatics in a typical electrophilic substitution.

PMID- 12236754
TI  - Steric control of organic transformation by a dendrimer cage: organocobalt
      dendrimer porphyrins as novel coenzyme B(12) mimics.
AB  - Cobalt(II) complexes of poly(aryl ester) dendrimer porphyrins (m-[Gn]TPP)Co(II)
      and (p-[Gn]TPP)Co(II) (n = 0-3) underwent AIBN-initiated alkylation (AIBN = 2,2'
      azobis(isobutyronitrile)) at the metal center with propargyl alcohol in CDCl(3)
      at 60 degrees C, where the dendritic substituents did not affect the overall
      conversion rate but selectivity of the alkylation. With the largest (m
      [G3]TPP)Co(II), a single organocobalt(III) species (Co(III)-C(=CH(2))CH(2)OH, 4)
      was selectively formed in 91% yield, due to a steric protection of 4 by the large
      dendrimer cage from the access of another molecule of cobalt porphyrin species.
      In contrast, with other cobalt(II) porphyrins, isomerized compounds such as
      Co(III)-C(CH(3))=CHOH (5) and Co(III)-CH(CH(3))CHO (6) were formed in addition to
      4. A stereochemical investigation with (m-[G3]TPP)Co(II) using AIBN-d(12), in
      place of nondeuterated AIBN, demonstrated that the alkylation (cobalt(III)
      hydride addition to propargyl alcohol) is selective to a trans adduct. Results
      also indicated that this addition step does not involve external activation of
      propargyl alcohol.

PMID- 12236755
TI  - On the mechanism of (PCP)Ir-catalyzed acceptorless dehydrogenation of alkanes: a
      combined computational and experimental study.
AB  - Pincer complexes of the type ((R)PCP)IrH(2), where ((R)PCP)Ir is [eta(3)-2,6
      (R(2)PCH(2))(2)C(6)H(3)]Ir, are the most effective catalysts reported to date for
      the "acceptorless" dehydrogenation of alkanes to yield alkenes and free H(2). We
      calculate (DFT/B3LYP) that associative (A) reactions of ((Me)PCP)IrH(2) with
      model linear (propane, n-PrH) and cyclic (cyclohexane, CyH) alkanes may proceed
      via classical Ir(V) and nonclassical Ir(III)(eta(2)-H(2)) intermediates. A
      dissociative (D) pathway proceeds via initial loss of H(2), followed by C-H
      addition to ((Me)PCP)Ir. Although a slightly higher energy barrier (DeltaE(+ +))
      is computed for the D pathway, the calculated free-energy barrier (DeltaG(+ +))
      for the D pathway is significantly lower than that of the A pathway. Under
      standard thermodynamic conditions (STP), C-H addition via the D pathway has
      DeltaG(o)(+ +) = 36.3 kcal/mol for CyH (35.1 kcal/mol for n-PrH). However,
      acceptorless dehydrogenation of alkanes is thermodynamically impossible at STP.
      At conditions under which acceptorless dehydrogenation is thermodynamically
      possible (for example, T = 150 degrees C and P(H)2 = 1.0 x 10(-7) atm), DeltaG(+
      +) for C-H addition to ((Me)PCP)Ir (plus a molecule of free H(2)) is very low
      (17.5 kcal/mol for CyH, 16.7 kcal/mol for n-PrH). Under these conditions, the
      rate-determining step for the D pathway is the loss of H(2) from ((Me)PCP)IrH(2)
      with DeltaG(D)(+ +) approximately DeltaH(D)(+ +) = 27.2 kcal/mol. For CyH, the
      calculated DeltaG(o)(+ +) for C-H addition to ((Me)PCP)IrH(2) on the A pathway is
      35.2 kcal/mol (32.7 kcal/mol for n-PrH). At catalytic conditions, the calculated
      free energies of C-H addition are 31.3 and 33.7 kcal/mol for CyH and n-PrH
      addition, respectively. Elimination of H(2) from the resulting "seven-coordinate"
      Ir-species must proceed with an activation enthalpy at least as large as the
      enthalpy change of the elimination step itself (DeltaH approximately 11-13
      kcal/mol), and with a small entropy of activation. The free energy of activation
      for H(2) elimination (DeltaG(A)(+ +)) is hence found to be greater than ca. 36
      kcal/mol for both CyH and n-PrH under catalytic conditions. The overall free
      energy barrier of the A pathway is calculated to be higher than that of the D
      pathway by ca. 9 kcal/mol. Reversible C-H(D) addition to ((R)PCP)IrH(2) is
      predicted to lead to H/D exchange, because the barriers for hydride scrambling
      are extremely low in the "seven-coordinate" polyhydrides. In agreement with
      calculation, H/D exchange is observed experimentally for several
      deuteriohydrocarbons with the following order of rates: C(6)D(6) > mesitylene
      d(12) > n-decane-d(22) >> cyclohexane-d(12). Because H/D exchange in cyclohexane
      d(12) solution is not observed even after 1 week at 180 degrees C, we estimate
      that the experimental barrier to cyclohexane C-D addition is greater than 36.4
      kcal/mol. This value is considerably greater than the experimental barrier for
      the full catalytic dehydrogenation cycle for cycloalkanes (ca. 31 kcal/mol).
      Thus, the experimental evidence, in agreement with calculation, strongly
      indicates that the A pathway is not kinetically viable as a segment of the
      "acceptorless" dehydrogenation cycle.

PMID- 12236756
TI  - The first example of a nitrile hydratase model complex that reversibly binds
      nitriles.
AB  - Nitrile hydratase (NHase) is an iron-containing metalloenzyme that converts
      nitriles to amides. The mechanism by which this biochemical reaction occurs is
      unknown. One mechanism that has been proposed involves nucleophilic attack of an
      Fe-bound nitrile by water (or hydroxide). Reported herein is a five-coordinate
      model compound ([Fe(III)(S(2)(Me2)N(3)(Et,Pr))](+)) containing Fe(III) in an
      environment resembling that of NHase, which reversibly binds a variety of
      nitriles, alcohols, amines, and thiocyanate. XAS shows that five-coordinate
      [Fe(III)(S(2)(Me2)N(3)(Et,Pr))](+) reacts with both methanol and acetonitrile to
      afford a six-coordinate solvent-bound complex. Competitive binding studies
      demonstrate that MeCN preferentially binds over ROH, suggesting that nitriles
      would be capable of displacing the H(2)O coordinated to the iron site of NHase.
      Thermodynamic parameters were determined for acetonitrile (DeltaH = -6.2(+/-0.2)
      kcal/mol, DeltaS = -29.4(+/-0.8) eu), benzonitrile (-4.2(+/-0.6) kcal/mol, DeltaS
      = -18(+/-3) eu), and pyridine (DeltaH = -8(+/-1) kcal/mol, DeltaS = -41(+/-6) eu)
      binding to [Fe(III)(S(2)(Me2)N(3)(Et,Pr))](+) using variable-temperature
      electronic absorption spectroscopy. Ligand exchange kinetics were examined for
      acetonitrile, iso-propylnitrile, benzonitrile, and 4-tert-butylpyridine using
      (13)C NMR line-broadening analysis, at a variety of temperatures. Activation
      parameters for ligand exchange were determined to be DeltaH(+ +) = 7.1(+/-0.8)
      kcal/mol, DeltaS(+ +) = -10(+/-1) eu (acetonitrile), DeltaH(+ +) = 5.4(+/-0.6)
      kcal/mol, DeltaS(+ +) = -17(+/-2) eu (iso-propionitrile), DeltaH(+ +) = 4.9(+/
      0.8) kcal/mol, DeltaS(+ +) = -20(+/-3) eu (benzonitrile), and DeltaH(+ +) =
      4.7(+/-1.4) kcal/mol DeltaS(+ +) = -18(+/-2) eu (4-tert-butylpyridine). The
      thermodynamic parameters for pyridine binding to a related complex,
      [Fe(III)(S(2)(Me2)N(3)(Pr,Pr))](+) (DeltaH = -5.9(+/-0.8) kcal/mol, DeltaS = 
      24(+/-3) eu), are also reported, as well as kinetic parameters for 4-tert
      butylpyridine exchange (DeltaH(+ +) = 3.1(+/-0.8) kcal/mol, DeltaS(+ +) = -25(+/
      3) eu). These data show for the first time that, when it is contained in a ligand
      environment similar to that of NHase, Fe(III) is capable of forming a stable
      complex with nitriles. Also, the rates of ligand exchange demonstrate that low
      spin Fe(III) in this ligand environment is more labile than expected.
      Furthermore, comparison of [Fe(III)(S(2)(Me2)N(3)(Et,Pr))](+) and
      [Fe(III)(S(2)(Me2)N(3)(Pr,Pr))](+) demonstrates how minor distortions induced by
      ligand constraints can dramatically alter the reactivity of a metal complex.

PMID- 12236757
TI  - Atomistic models for CeO(2)(111), (110), and (100) nanoparticles, supported on
      yttrium-stabilized zirconia.
AB  - Ceria is an important component in three-way catalysts for the treatment of
      automobile exhaust gases owing to its ability to store and release oxygen, a
      property known as the oxygen storage capacity. Much effort has been focused on
      increasing the OSC of ceria, and one avenue of exploration is the ability to
      fabricate CeO(2)-based catalysts, which expose reactive surfaces. Here we show
      how models for a polycrystalline CeO(2) thin film, which expose the (111), (110),
      and dipolar (100) surfaces, can be synthesized. This is achieved by supporting
      the CeO(2) thin film on an yttrium-stabilized zirconia substrate using a
      simulated amorphization and recrystallization strategy. In particular, the
      methodology generates models which reveal the atomistic structures present on the
      surface of the reactive faces and provides details of the grain-boundary
      structures, defects (vacancies, substitutionals, and clustering), and epitaxial
      relationships. Such models are an important first step in understanding the
      active sites at the surface of a catalytic material.

PMID- 12236758
TI  - Interaction between f-electronic systems in dinuclear lanthanide complexes with
      phthalocyanines.
AB  - The first detection and characterization of the interactions between the f
      electronic systems in the dinuclear complexes of paramagnetic trivalent Tb, Dy,
      Ho, Er, Tm, and Yb ions with phthalocyanine ligands are presented. The molar
      magnetic susceptibilities, chi(m), were measured for PcLnPcLnPc* ([Ln, Ln]; Pc =
      dianion of phthalocyanine, Pc* = dianion of 2,3,9,10,16,17,23,24
      octabutoxyphthalocyanine) and PcLnPcYPc* ([Ln, Y]) in the range from 1.8 K to
      room temperature. The selective synthetic method previously reported for the
      heterodinuclear complex [Y, Ln] was used to prepare [Ln, Ln] and [Ln, Y] with a
      modification on the choice of starting materials. The f-f interaction
      contributions to the magnetic susceptibility are evaluated as Delta(chi)(m)T =
      chi(m)([Ln, Ln])T - chi(m)([Ln, Y])T - chi(m)([Y, Ln])T, where T refers to
      temperature on the kelvin scale. The homodinuclear complexes having f(8)-f(10)
      systems, namely [Tb, Tb], [Dy, Dy], and [Ho, Ho], show positive Delta(chi)(m)T
      values in the 1.8-50 K range, indicating the existence of ferromagnetic
      interaction between the f-systems. The magnitude of the Delta(chi)(m)T increases
      in the descending order of the number of f-electrons. [Er, Er] gives negative
      Delta(chi)(m)T values in the 1.8-50 K range, showing the antiferromagnetic nature
      of the f-f interaction. [Tm, Tm] exhibits small and negative Delta(chi)(m)T
      values, which gradually decline in the negative direction as the temperature
      decreases in the range 13-50 K and sharply rise in the positive direction as the
      temperature falls from 10 to 1.8 K. [Yb, Yb] has extremely small Delta(chi)(m)T
      values, whose magnitude at 2 K is less than 1% of that of [Tb, Tb]. The ligand
      field parameters of the ground-state multiplets of the six [Ln, Y] complexes are
      determined by simultaneous fitting to both the magnetic susceptibility data and
      paramagnetic shifts of (1)H NMR. The theoretical analysis successfully converged
      by assuming that each ligand field parameter is a function of the number of f
      electrons in each ion. Using these parameters as well as the previously obtained
      corresponding parameters for the [Y, Ln] series, the interactions between the f
      systems in [Ln, Ln] are investigated. All the characteristic observations above
      are satisfactorily reproduced with the assumption that the magnetic dipolar term
      is the sole source of the f-f interaction.

PMID- 12236759
TI  - Mechanism of the photochemical ligand substitution reactions of fac
      [Re(bpy)(CO)(3)(PR(3))](+) complexes and the properties of their triplet ligand
      field excited states.
AB  - We report herein the mechanism of the photochemical ligand substitution reactions
      of a series of fac-[Re(X(2)bpy)(CO)(3)(PR(3))](+) complexes (1) and the
      properties of their triplet ligand-field ((3)LF) excited states. The reason for
      the photostability of the rhenium complexes [Re(X(2)bpy)(CO)(3)(py)](+) (3) and
      [Re(X(2)bpy)(CO)(3)Cl] (4) was also investigated. Irradiation of an acetonitrile
      solution of 1 selectively gave the biscarbonyl complexes cis,trans
      [Re(X(2)bpy)(CO)(2)(PR(3))(CH(3)CN)](+) (2). Isotope experiments clearly showed
      that the CO ligand trans to the PR(3) ligand was selectively substituted. The
      photochemical reactions proceeded via a dissociative mechanism from the (3)LF
      excited state. The thermodynamical data for the (3)LF excited states of complexes
      1 and the corrective nonradiative decay rate constants for the triplet metal-to
      ligand charge-transfer ((3)MLCT) states were obtained from temperature-dependence
      data for the emission lifetimes and for the quantum yields of the photochemical
      reactions and the emission. Comparison of 1 with [Re(X(2)bpy)(CO)(3)(py)](+) (3)
      and [Re(X(2)bpy)(CO)(3)Cl] (4) indicated that the (3)LF states of some 3- and 4
      type complexes are probably accessible from the (3)MLCT state even at ambient
      temperature, but these complexes were stable to irradiation at 365 nm. The
      photostability of 3 and 4, in contrast to 1, can be explained by differences in
      the trans effects of the PR(3), py, and Cl(-) ligands.

PMID- 12236760
TI  - Oxidative addition of water and aliphatic alcohols by IrCl(trialkylphosphine)(3).
AB  - Oxidative addition of aliphatic alcohols to (C(8)H(14))IrCl(PMe(3))(3) in benzene
      yields the cis-hydrido-alkoxo products mer-cis-HIr(OR)Cl(PMe(3))(3) (R = Me, Et,
      1-pentyl, 2-propyl). The analogous hydroxo complex is prepared by oxidative
      addition of water in THF. The addition rate depends on the nature of the alcohol
      (methanol > 1-pentanol >> 2-propanol and methanol > water). The reaction is
      retarded in polar media but accelerated by protic cosolvents. Anionic ligand
      redistribution involving chloride and alkoxide (or hydroxide) competes with the
      oxidative addition reaction. A detailed kinetic study suggests that the 16
      electron IrCl(PMe(3))(3) is the species undergoing the oxidative addition, and
      mer-cis-HIr(OR)Cl(PMe(3))(3) is the kinetic product. The reaction proceeds by a
      single-step nucleophilic attack of the metal on the O-H proton. Pi-donation by
      chloride stabilizes the transition state and governs the stereochemical course of
      the reaction. Protic solvent aggregation in the transition state in an apolar
      medium is suggested. mer-cis-HIr(OH)Cl(PEt(3))(3), obtained by water addition to
      IrCl(PEt(3))(3), was crystallographically characterized, showing an unusual
      hydrophobic cage around the hydride ligand.

PMID- 12236761
TI  - Chemistry of the strong electrophilic metal fragment [(99)Tc(N)(PXP)](2+) (PXP =
      diphosphine ligand). A novel tool for the selective labeling of small molecules.
AB  - Monosubstituted [M(N)Cl(2)(POP)] [M = Tc, 1; Re, 2] and [M(N)Cl(2)(PNP)] [M = Tc,
      3; Re, 4] complexes were prepared by reaction of the precursors [M(N)Cl(4)](-)
      and [M(N)Cl(2)(PPh(3))(2)] (M = Tc, Re) with the diphosphine ligands bis(2
      diphenylphosphinoethyl)ether (POP) and bis(2
      diphenylphosphinoethyl)methoxyethylamine (PNP) in refluxing
      dichloromethane/methanol solutions. In these compounds, the diphosphine acted as
      a chelating ligand bound to the metal center through the two phosphorus atoms.
      Considering also the weak interaction of the heteroatom (N or O) located in the
      middle of the carbon backbone connecting the two P atoms, we found that the
      coordination arrangement of the diphosphine ligand could be viewed as either
      meridional (m) or facial (f), and the resulting geometry as pseudooctahedral. The
      heteroatom of the diphosphine ligand was invariably located trans to the nitrido
      linkage, as established by X-ray diffraction analysis of the representative
      compounds 2m and 4f. Density functional theoretical calculations showed that in
      POP-type complexes the mer form is favored by approximately 6 kcal mol(-1),
      whereas mer and fac isomers are almost isoenergetic in PNP-type complexes. A
      possible role of noncovalent interactions between the phosphinic phenyl
      substituents in stabilizing the fac-isomer was also highlighted. The existence of
      fac-mer isomerism in this class of complexes was attributed to the strong
      tendency of the two phosphorus atoms to occupy a reciprocal trans-position within
      the pseudooctahedral geometry. The switching of P atoms between cis- and trans
      configurations was confirmed by the observation that the fac isomers, 1f and 2f,
      were irreversibly transformed, in solution, into the corresponding mer isomers,
      1m and 2m, thus suggesting that fac complexes are more reactive species.
      Theoretical calculations supported this view by showing that the lowest
      unoccupied orbitals of the fac isomers are more accessible to a nucleophilic
      attack with respect to those of the mer ones. Furthermore, the large
      participation of the Cl orbitals to the HOMO, which is a metal-ligand pi*
      antibonding in the complex basal plane, shows that the Tc-Cl bonds are labile. As
      a consequence, facial isomers could be considered as highly electrophilic
      intermediates that were selectively reactive toward substitution by electron-rich
      donor ligands. Experimental evidence was in close agreement with this
      description. It was found that fac-[M(N)Cl(2)(PXP)] complexes easily underwent
      ligand-exchange reactions with bidentate donor ligands such as mercaptoacetic
      acid (NaHL(1)), S-methyl 2-methyldithiocarbazate (H(2)L(2)),
      diethyldithiocarbamate sodium salt (NaL(3)), and N-acetyl-L-cysteine (H(2)L(4))
      to afford stable asymmetrical heterocomplexes of the type fac
      [M(N)(L(n))(POP)](+/0) (5-8) and fac-[M(N)(L(n))(PNP)](+/0) (9-14) comprising two
      different polydentate chelating ligands bound to the same metal center. In these
      reactions, the bidentate ligand replaced the two chloride atoms on the equatorial
      plane of the distorted octahedron, leaving the starting fac-[M(N)(PXP)](2+) (X =
      O, N) moieties untouched. No formation of the corresponding symmetrical complexes
      containing two identical bidentate ligands was detected over a broad range of
      experimental conditions. Solution-state NMR studies confirmed that the structure
      in solution of these heterocomplexes was identical to that established in the
      solid state by X-ray diffraction analysis of the prototype complexes fac
      [M(N)(HL(2))(POP)][BF(4)] [M = Tc, 7; Re, 8] and fac-[Tc(N)(HL(2))(PNP)][BF(4)],
      11. In conclusion, the novel metal fragment fac-[M(N)(PXP)](2+) could be utilized
      as an efficient synthon for the preparation of a large class of asymmetrical,
      nitrido heterocomplexes incorporating a particular diphosphine ligand and a
      variety of bidentate chelating molecules.

PMID- 12236762
TI  - Colloidal synthesis and self-assembly of CoPt(3) nanocrystals.
AB  - Reduction of platinum acetylacetonate and thermodecomposition of cobalt carbonyl
      in the presence of 1-adamantanecarboxylic acid were employed in different
      coordinating mixtures to produce monodisperse, highly crystalline CoPt(3)
      nanoparticles. The mean particle size can be varied from 1.5 to 7.2 nm by
      controlling the reaction conditions and the type of coordinating mixture. As
      synthesized CoPt(3) particles represent single crystal domains and have
      chemically disordered face-centered cubic (fcc) structure. Nearly spherical
      CoPt(3) nanocrystals were found to assemble into two- (2D) and three-dimensional
      (3D) structures. An AB(5) type superlattice is observed by TEM after mixing two
      nanoparticle samples with different mean sizes. Slow precipitation led to the
      formation of facetted colloidal crystals with sizes up to 20 microm.

PMID- 12236763
TI  - Divergent pathways of C-H bond activation: reactions of (t-Bu(3)PN)(2)TiMe(2)
      with trimethylaluminum.
AB  - The reaction of AlMe(3) with (t-Bu(3)PN)(2)TiMe(2) 1 proceeds via competitive
      reactions of metathesis and C-H activation leading ultimately to two Ti
      complexes: [(mu(2)-t-Bu(3)PN)Ti(mu-Me)(mu(4)-C)(AlMe(2))(2)](2) 2, [(t
      Bu(3)PN)Ti(mu(2)-t-Bu(3)PN)(mu(3)-CH(2))(2)(AlMe(2))(2)(AlMe(3))] 3, and the
      byproduct (Me(2)Al)(2)(mu-CH(3))(mu-NP(t-Bu(3))) 4. X-ray structural data for 2
      and 3 are reported. Compound 3 undergoes thermolysis to generate a new species
      [Ti(mu(2)-t-Bu(3)PN)(2)(mu(3)-CH(2))(mu(3)-CH)(AlMe(2))(3)] 5. Monitoring of the
      reaction of 1 with AlMe(3) by (31)P[(1)H] NMR spectroscopy revealed intermediates
      including (t-Bu(3)PN)TiMe(3) 6. Compound 6 was shown to react with AlMe(3) to
      give 2 exclusively. Kinetic studies revealed that the sequence of reactions from
      6 to 2 involves an initial C-H activation that is a second-order reaction,
      dependent on the concentration of Ti and Al. The second-order rate constant k(1)
      was 3.9(5) x 10(-4) M(-1) s(-1) (DeltaH(#) = 63(2) kJ/mol, DeltaS(#) = -80(6)
      J/mol x K). The rate constants for the subsequent C-H activations leading to 2
      were determined to be k(2) = 1.4(2) x 10(-3) s(-1) and k(3) = 7(1) x 10(-3) s(
      1). Returning to the more complex reaction of 1, the rate constant for the ligand
      metathesis affording 4 and 6 was k(met) = 6.1(5) x 10(-5) s(-1) (DeltaH(#) =
      37(3) kJ/mol, DeltaS(#) = -203(9) J/mol x K). The concurrent reaction of 1
      leading to 3 was found to proceed with a rate constant of k(obs) of 6(1) x 10(-5)
      s(-1) (DeltaH(#) = 62(5) kJ/mol, DeltaS(#)= -118(17) J/mol x K). Using these
      kinetic data for these reactions, a stochastic kinetic model was used to compute
      the concentration profiles of the products and several intermediates with time
      for reactions using between 10 and 27 equivalents of AlMe(3). These models
      support the view that equilibrium between 1 x AlMe(3) and 1 x (AlMe(3))(2)
      accounts for varying product ratios with the concentration of AlMe(3). In a
      similar vein, similar equilibria account for the transient concentrations of 6
      and an intermediate en route to 3. The implications of these reactions and
      kinetic and thermodynamic data for both C-H bond activation and deactivation
      pathways for Ti-phosphinimide olefin polymerization catalysts are considered and
      discussed.

PMID- 12236764
TI  - Magnetic ordering in doped Cd(1-x)Co(x)Se diluted magnetic quantum dots.
AB  - In this study, we report structural, vibrational, and magnetic data providing
      evidence of random ion displacement in the core of CdSe quantum dots on the
      Cd(2+) sites by Co(2+) ions (between x = 0 and 0.30). Structural evidence for
      core doping is obtained by analyzing the powder X-ray diffraction (pXRD), data
      which exhibits a linear lattice compression with increasing Co(2+) concentration,
      in accord with Vegard's law. Correlated with the pXRD shift, a hardening of the
      CdSe longitudinal optical phonon mode and a new local vibrational mode are
      observed which track Co(2+) doping concentration. Consistent with the observed
      core doping, superconducting quantum interference device (SQUID) measurements
      indicate a surprising increase for the onset of spin glass behavior by an order
      of magnitude over bulk Co:CdSe. Correlation of SQUID results, pXRD, and Raman
      measurements suggests that the observed enhancement of magnetic superexchange
      between Co(2+) dopant ions in this confined system arises from changes in the
      nature of coupling in size-restricted materials.

PMID- 12236765
TI  - Insights into the free-energy dependence of intramolecular dissociative electron
      transfers.
AB  - To study the relationship between rate and driving force of intramolecular
      dissociative electron transfers, a series of donor-spacer-acceptor (D-Sp-A)
      systems has been devised and synthesized. cis-1,4-Cyclohexanedyil and a perester
      functional group were kept constant as the spacer and acceptor, respectively. By
      changing the aryl substituents of the phthalimide moiety, which served as the
      donor, the driving force could be varied by 0.74 eV. X-ray diffraction
      crystallography and ab initio conformational calculations pointed to D-Sp-A
      molecules having the cis-(cyclohexane) equatorial(phthalimido)-axial(perester)
      conformation and the same D/A orientation. The intramolecular dissociative
      electron-transfer process was studied by electrochemical means in N,N
      dimethylformamide, in comparison with thermodynamic and kinetic information
      obtained with models of the acceptor and the donor. The intramolecular process
      consists of the electron transfer from the electrochemically generated
      phthalimide-moiety radical anion to the peroxide functional group. The
      electrochemical analysis provided clear evidence of a concerted dissociative
      electron-transfer mechanism, leading to the cleavage of the O-O bond. Support for
      this mechanism was obtained by ab initio MO calculations, which provided
      information about the LUMO of the acceptor and the SOMO of the donor. The
      intramolecular rate constants were determined and compared with the corresponding
      intermolecular values, the latter data being obtained by using the model
      molecules. As long as the effective location of the centroid of the donor SOMO
      does not vary significantly by changing the aryl substituent(s), the
      intramolecular dissociative electron transfer obeys the same main rules already
      highlighted for the corresponding intermolecular process. On the other hand,
      introduction of a nitro group drags the SOMO away from the acceptor, and
      consequently, the intramolecular rate drops by as much as 1.6 orders of magnitude
      from the expected value. Therefore, a larger solvent reorganization than for
      intermolecular electron transfers and the effective D/A distance and thus
      electronic coupling must be taken into account for quantitative predictions of
      intramolecular rates.

PMID- 12236766
TI  - Hot-fluid annealing for crystalline titanium dioxide nanoparticles in stable
      suspension.
AB  - Titanium dioxide (TiO(2)) nanoparticles were synthesized by controlled hydrolysis
      of titanium alkoxide in reverse micelles in a hydrocarbon solvent. Upon annealing
      in situ in the presence of the micelles at temperatures considerably lower than
      those required for the traditional calcination treatment in the solid state, the
      TiO(2) nanoparticles became highly crystalline but still maintained the same
      physical parameters and remained in a stable suspension. Thus, the method has
      allowed the preparation of crystalline TiO(2) nanoparticles that are
      monodispersed in the same way as they are initially produced in the
      microemulsion. Effects of the fluid properties on the crystallization of
      nanoparticles are discussed.

PMID- 12236767
TI  - Charged states of proteins. Reactions of doubly protonated alkyldiamines with
      NH(3): solvation or deprotonation. Extension of two proton cases to multiply
      protonated globular proteins observed in the gas phase.
AB  - The apparent gas-phase basicities (GB(app)'s) of basic sites in multiply
      protonated molecules, such as proteins, can be approximately predicted. An
      approach used by Williams and co-workers was to develop an equation for a
      diprotonated system, NH(3)(CH(2))(7)NH(3)(2+), and then extend it with a
      summation of pairwise interactions to multiply protonated systems. Experimental
      determinations of the rates of deprotonation of NH(3)(CH(2))(7)NH(3)(2+) by a
      variety of bases B, in the present work, showed that GB(app) = GB(NH(3)) = 196
      kcal/mol. This result is supported also by determinations of the equilibria:
      NH(3)(CH(2))(p)NH(3)(2+) + NH(3) = NH(3)(CH(2))(p)NH(3) x NH(3)(2+), for p = 7,
      8, 10, 12. The described experimental GB(app) is 14 kcal/mol higher than the
      value predicted by the equation used by Williams and co-workers but in agreement
      with an ab initio result by Gronert. Equations based on electrostatics are
      developed for the two proton and multiproton systems which allow the evaluation
      of GB(app) of the basic sites on proteins. These are applied for the evaluation
      of GB(app) of the basic sites and of N(SB), the maximum number of protons that
      the nondenatured proteins, carbonic anhydrase (CAII), cytochrome c (CYC), and
      pepsin, can hold. The N(SB) values are compared with the observed charges,
      Z(obs)'s, when the nondenatured proteins are produced by electrospray and found
      in agreement with the proposal by de la Mora that Z(obs) is determined by the
      number of charges provided by the droplet that contains the protein, according to
      the charge residue model (CRM). The GB(app) values of proteins have many other
      applications. They can be compared with experimental measurements and are also
      needed for the understanding of the thermal denaturing of charged proteins and
      the thermal dissociation of charged protein complexes.

PMID- 12236768
TI  - Conformational and spectroscopic analysis of the tyrosyl radical dipeptide
      analogue in the gas phase and in aqueous solution by a density
      functional/continuum solvent model.
AB  - The conformational and spectroscopic properties of the tyrosyl radical dipeptide
      analogue (T(R)DA) are investigated both in gas phase and in aqueous solution by
      means of density functional calculations. Electronic interactions between
      backbone and side chain, determining the relative stability of the different
      energy minimums, depend on the electronic state of the phenoxy substituent. As a
      consequence, (i) the conformational behavior of T(R)DA is quite different from
      that of the tyrosine dipeptide analogue, and (ii) the energy required for the
      homolytic breaking of the OH bond depends on the adopted conformation. The
      calculated hyperfine coupling constants are in good agreement with the available
      experimental results. Side-chain-backbone interactions cause an asymmetrization
      of the magnetic properties of the phenoxy ring and deviations from McConnell
      relationship. Solvent effects, taken into account by means of a combined
      discrete/continuum model, significantly affect both the conformational and the
      magnetic behavior of T(R)DA.

PMID- 12236769
TI  - Photoinduced energy- and electron-transfer processes within dynamic self
      assembled donor-acceptor arrays.
AB  - The synthesis and the photophysical properties of a series of noncovalently
      assembled donor-acceptor systems, dyads, is reported. The presented approach uses
      an "innocent" coordination compound, a scandium(III) acetyl acetonate derivative,
      as core and promotor of the dyad formation. Intercomponent photoinduced energy
      transfer or electron transfer within the dynamic assembly, which yields to a
      statistical library of donor-acceptor systems, is reported. The assemblies for
      energy-transfer processes are constituted by an energy donor, Ru(bpy)(3)(2+)
      based component (bpy = 2,2'-bipyridine), and by an energy-acceptor moiety,
      anthracene-based unit, both substituted with a chelating ligand, acetyl acetone,
      that via coordination with a scandium ion will ensure the formation of the dyad.
      If N,N,N'N'-tetramethyl-2,5-diaminobenzyl-substituted acetyl acetonate ligands
      are used in the place of 9-acyl-anthracene, intramolecular photoinduced electron
      transfer from the amino derivative (electron donor) to the Ru(bpy)(3)(2+)-unit
      was detected upon self-assembly, mediated by the scandium complex. The
      photophysical processes can be studied on the lifetime of the kinetically labile
      complexes.

PMID- 12236770
TI  - Isotope effects and the mechanism of an electron-transfer-catalyzed Diels-Alder
      reaction.
AB  - The electron-transfer-catalyzed Diels-Alder reaction of indole and 1,3
      cyclohexadiene was studied by a combination of experimental and theoretical
      methods. The (13)C kinetic isotope effects were determined at natural abundance
      by NMR methodology. B3LYP/6-31G* calculations allow for the first time a
      quantitatively accurate description of the different possible pathways and
      provide the basis for an analysis of the experimentally observed isotope effects.
      The computational results, in conjunction with experimental observations, show
      that the reaction has a stepwise mechanism that is initiated by attack of the
      diene into the 3-position of the indole. Numerical simulation of the
      experimentally observed isotope effects shows that the first step is rate
      determining and that the electron exchange in the reactant contributes partially
      to the overall isotope effect. The combination of electronic structure theory,
      experimental isotope effects, and numerical simulation thus allows a detailed
      analysis of a complex reaction mechanism.

PMID- 12236771
TI  - Photoswitching of ligand association with a photoresponsive polymer-protein
      conjugate.
AB  - Light-regulated molecular switches that reversibly control biomolecular function
      could provide new opportunities for controlling activity in diagnostics, affinity
      separations, bioprocessing, therapeutics, and bioelectronics applications. Here
      we show that site-specific conjugation of light-responsive polymers near the
      biotin-binding pocket of streptavidin provides control of ligand binding affinity
      in response to UV and visible light irradiation. Two different light-responsive
      polymers were utilized that display opposite photoresponsive solubility changes
      under UV or visible (vis) light irradiation in aqueous solutions. At 40 degrees
      C, the N,N-dimethylacrylamide (DMA)-co-4-phenylazophenyl acrylate (AZAA)
      copolymer (DMAA) was soluble under UV irradiation and precipitated under visible
      light, while the DMA-co-N-4-phenylazophenyl acrylamide (AZAAm) copolymer (DMAAm)
      was soluble under visible irradiation and precipitated under UV light. Both
      polymers were synthesized with a vinyl sulfone terminus and conjugated to the
      Glu116Cys (E116C) streptavidin mutant via thiol coupling. The DMAA-streptavidin
      conjugate bound biotin efficiently when the polymer was in the soluble state
      under UV irradiation, but under visible irradiation, the polymer collapsed and
      blocked free biotin association. Furthermore, if biotin was allowed to bind when
      the polymer was in the soluble state under UV irradiation, then when the polymer
      was collapsed by visible light, the streptavidin released the bound biotin. The
      DMAAm-streptavidin conjugate showed the opposite response, with association of
      biotin allowed under visible light irradiation and blocked under UV irradiation.
      The photoresponses of the streptavidin conjugates thus correspond to the original
      photoresponsive phase transition properties of the polymer switches triggered by
      the cis-trans isomerization of the diazo chromophores.

PMID- 12236772
TI  - Local delivery of basic fibroblast growth factor (bFGF) using adsorbed silyl
      heparin, benzyl-bis(dimethylsilylmethyl)oxycarbamoyl-heparin.
AB  - A growth factor delivery system was developed that is based on the use of silyl
      heparin, a chemically modified analogue of heparin. The silyl-heparin was
      adsorbed onto surfaces by hydrophobic interaction via the prosthetic unit and can
      then be used as a solid-phase adsorbent for bFGF. All the coating steps were
      performed by adsorption, a process that allowed preparation of surfaces by
      immersion or "dip-coating". In this study a series of silyl-heparins were
      synthesized and each of the analogues found to function similar to unmodified
      heparin relative to their binding of antithrombin III and also the binding of
      bFGF. The silyl-heparins were found to be adsorbed onto a wide variety of
      substrates including polystyrene and lactide:glycolide copolymer. Enzyme-linked
      immumosorbant assay (ELISA) was used to establish that bFGF was readily bound to
      surface adsorbed silyl-heparin, and that the amount bound was directly related to
      amount offered for binding. Once adsorbed the silyl-heparin/FGF was able to
      induce capillary tube formation of endothelial cells and to increase the growth
      of endothelial cells. When coated onto suture material and implanted in muscle,
      the FGF/silyl-heparin coating caused an increased density of mesenchymal cells in
      the area of the implant. This coating method could prove to be useful in a number
      of tissue engineering applications for the local delivery of FGF and other growth
      factors.

PMID- 12236773
TI  - NMR characterization of the DNA binding properties of a novel Hoechst 33258
      analogue peptide building block.
AB  - A novel aryl-bis-benzimidazole amino acid analogue of the DNA-binding compound
      Hoechst 33258 has recently been designed for incorporation in peptide
      combinatorial libraries by replacing the N-methylpiperazine group with a carboxyl
      group and the hydroxy group with an amino-methyl group. The DNA-binding
      properties of the aryl-bis-benzimidazole monomer with the C-terminus derivatized
      with 3-(dimethylamino)-propylamine has been investigated in this paper by (1)H
      NMR studies of two different complexes with two different DNA sequences: A(5)
      d(5'-GCCA(5)CG-3'):d(5'-CGT(5)GGC-3') and A(3)T(3) d(5'-CGA(3)T(3)CG-3')(2).
      Chemical shift footprinting shows that the ligand binds at the center of the
      A(3)T(3) sequence but at the 3'-end of A(5). A large number of NOEs show a well
      defined complex with the ligand situated at the center of the palindromic
      A(3)T(3) but with the asymmetric A(5) the ligand binds with an orientational
      preference with the bis-benzimidazole moiety displaced toward the 3'-end from the
      center of the duplex. Two families of models of the complexes with A(5) and
      A(3)T(3) were derived with restrained molecular dynamics based on a large set of
      70 and 61, respectively, intermolecular ligand NOEs. Both models give a picture
      of a tightly fitting ligand with close van der Waals contacts with the walls of
      the minor groove and with the two benzimidazole and the amide hydrogens involved
      in bifurcated cross-strand hydrogen bonds to adenine N3 and thymine O2. The minor
      groove width of the models correlate well with the binding site of the ligand,
      and the orientational preference is argued to be a consequence of the minor
      groove width and hydrogen bonding.

PMID- 12236774
TI  - Design and formulation of polyplexes based on pluronic-polyethyleneimine
      conjugates for gene transfer.
AB  - Previously, we reported the evaluation of several polyplex-based gene delivery
      systems with respect to their effectiveness, toxicity, and cell type dependence
      in vitro. One system, P123-g-PEI(2K), a cationic graft block copolymer, is of
      particular interest as it has been demonstrated to successfully deliver genetic
      material to murine liver following systemic delivery [Nguyen, H. K., Lemieux, P.,
      Vinogradov, S. V., Gebhart, C. L., Guerin, N., Paradis, G., Bronich, T. K.,
      Alakhov, V. Y., and Kabanov, A. V. (2000) Evaluation of Polyether
      Polyethyleneimine Graft Copolymers as Gene Transfer Agents. Gene Ther. 7, 126-138
      (1)]. The P123-g-PEI(2K) system requires nonmodified Pluronic P123 as an
      excipient to stabilize the dispersion. The purpose of the current work was to
      more closely characterize this system, to assess the role of each component of
      the system to the overall transfection process. We evaluated particle size,
      stability, and resistance to nuclease degradation. In addition, cellular uptake
      and localization of plasmid, as well as transgene expression, were evaluated
      following in vitro transfection of prostate cancer cells (PC-3) with various
      individual components of the system. Nonmodified Pluronic alone did not
      significantly enhance DNA uptake, transgene expression, or DNase protection.
      Therefore, we conclude that nonmodified Pluronic acted primarily by optimizing
      the size of the polyplex. Furthermore, though this system displays several
      characteristics thought desirable of a nonviral gene delivery system, these
      studies did discriminate a potential limitation of this system for in vivo
      applications, namely, the insufficient level of protection of plasmid DNA from
      nuclease degradation. This may limit the effective dose delivered, as well as
      limiting the effective circulation time. These studies provide vital information
      that will guide modification of this system to enhance the current in vivo
      profile.

PMID- 12236775
TI  - Artificial ribonucleases: efficient and specific in vitro cleavage of human c-raf
      1 RNA.
AB  - We report here the first successful sequence-specific cleavage of large RNA using
      artificial ribonucleases. A series of uniformly 2'-methoxyethoxy-modified
      oligonucleotides bearing a europium complex were investigated as artificial
      ribonucleases specific for the human c-raf-1 mRNA. The efficiency and specificity
      of these oligonucleotide-metal conjugates to bind and to cleave 571 and 2,977
      nucleotides long c-raf-1 RNA transcripts in vitro in a sequence-specific manner
      is demonstrated. Quantitative analysis reveals a cleavage efficiency of 60-70%
      within 4 h at 37 degrees C. Precise mapping of cleavage sites using primer
      extension analysis shows that cleavage generally occurs at two or three major
      sites adjacent to the 3'-end of the RNA target region. Cleavage is preferentially
      observed after purine nucleotides. This study demonstrates the potency of
      artificial ribonucleases targeting large, biologically relevant RNAs.

PMID- 12236776
TI  - Biodegradable, endosome disruptive, and cationic network-type polymer as a highly
      efficient and nontoxic gene delivery carrier.
AB  - The success of gene therapy is largely dependent on the delivery vector system.
      Efficient transfection and nontoxicity are two of the most important requirements
      of an ideal gene delivery vector. To generate both an efficient and nontoxic
      vector, we rationally constructed polymeric vectors to have simultaneous multiple
      functions, i.e., controlled degradation, an endosome disruptive function, and
      positive charges. Remarkably, the transfection efficiency of network poly(amino
      ester) (n-PAE) synthesized in this manner was comparable to that of
      polyethylenimine (PEI), one of the most efficient polymeric gene delivery vectors
      reported to date. However, there was a marked difference in cytotoxicity between
      the polymers. The majority of PEI-transfected cells were granulated and dead,
      whereas most of the cells transfected with n-PAE were viable and healthy.
      Successive events of efficient endosome escape of n-PAE/DNA polyplex and n-PAE
      biodegradation should result in high transfection efficiency and favorable cell
      viability response. The n-PAE-mediated transfection was also very efficient in
      the presence of serum. These data show that the approach we applied is a very
      appropriate way of making an ideal gene delivery carrier.

PMID- 12236777
TI  - Solid phase assembly of defined protein conjugates.
AB  - We have developed a solid-phase procedure for protein-protein conjugation that
      gives greater control over product size and composition than previous methods.
      Conjugates are assembled by sequential addition of activated proteins to the
      support under conditions suitable for maintaining the activity of the proteins.
      The total number of conjugate units to be prepared is fixed in the first step by
      the quantity of the first protein absorbed by the support. In each following
      step, the added protein links only to previously bound protein. The final
      conjugate is released to solution by cleaving the linker holding the first
      protein to the support. This stepwise assembly provides uniformly sized
      conjugates of the desired size and composition with placement of components at
      the desired positions within the structure. Using this approach, we have prepared
      a series of conjugates containing R-phycoerythrin as the central protein, with
      varying quantities of alkaline phosphatase and IgG with expected molecular masses
      ranging from 1.6 to 11.5 MDa. Size-exclusion chromatography and atomic force
      microscopy demonstrate homogeneity and control of the conjugate size. In an
      immunoassay for human thyroid stimulating hormone, the conjugates show signals
      consistent with their compositions.

PMID- 12236778
TI  - Conjugation of ligands at the 5'-end of CpG DNA affects immunostimulatory
      activity.
AB  - Bacterial DNA and synthetic oligonucleotides containing unmethylated CpG
      dinucleotides (CpG DNA) activate the vertebrate immune system and promote Th1
      like immune responses. Several CpG DNAs are currently being tested in clinical
      trials as either alone or in combination with vaccines, antibodies, and allergens
      separately or as conjugates for a number of disease indications including
      cancers, allergies, and asthma. In this paper, we show that conjugation of an
      oligonucleotide and a CpG DNA through their 5'-ends (5'-5'-linked DNA)
      significantly reduces the immunostimulatory activity of the CpG DNA. In addition,
      we found that the reduction in immunostimulatory activity of 5'-5'-linked CpG DNA
      depends on the size of the oligonucleotide conjugated to CpG DNA. Conjugation of
      a smaller group or molecule, such as a phosphorothioate group, at the 5'-end of
      CpG DNA has an insignificant effect on immunostimulatory activity. However,
      conjugation of a mononucleotide, tetra- or longer oligonucleotide or a
      fluorescein molecule to the 5'-end of a CpG DNA (5'-5'-linked DNA) significantly
      suppresses the immunostimulatory activity of CpG DNA. Surprisingly, conjugation
      of an oligonucleotide or a ligand through the 3'-end of CpG DNA (3'-3'-linked
      DNA) has an insignificant effect on immunostimulatory activity. Studies of
      cellular uptake and activation of transcription factor NF-kappaB in J774 cells
      using fluorescein-conjugated CpG DNAs suggest that the differences in the immune
      stimulation of 5'- and 3'-end-conjugated CpG DNAs is not as a result of
      differences in their cellular uptake properties. These results suggest that for
      optimal immunostimulatory activity, ligands should not be attached at the 5'-end
      of the CpG DNA.

PMID- 12236779
TI  - Antisense oligonucleotides delivered to the lysosome escape and actively inhibit
      the hepatitis B virus.
AB  - The subcellular fate and activity in inhibiting the hepatitis B virus of free and
      N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-phosphorothioate
      oligonucleotides were studied. Their internalization and subcellular fate were
      monitored with confocal microscopy. A fraction of the internalized free
      oligonucleotides escaped into the cytoplasm and nucleus of Hep G2 cells but were
      not active antiviral agents. Covalently attaching the oligonucleotides to the
      HPMA copolymers via nondegradable dipeptide GG spacers resulted in sequestering
      the oligonucleotides in vesicles after internalization. Conjugation of the
      oligonucleotides to an HPMA copolymer via a lysosomally cleavable tetrapeptide
      GFLG spacer resulted in release of the oligonucleotide in the lysosome and
      subsequent translocation into the cytoplasm and nucleus of the cells. The HPMA
      copolymer-oligonucleotide conjugate possessed antiviral activity, indicating that
      phosphorothioate oligonucleotides released from the carrier in the lysosome were
      able to escape into the cytoplasm and nucleus and remain active. The Hep G2 cells
      appeared to actively internalize the phosphorothioate oligonucleotides as
      oligonucleotide-HPMA copolymer conjugates were internalized to a greater extent
      than unconjugated polymers.

PMID- 12236780
TI  - Reduction of kidney uptake in radiometal labeled peptide linkers conjugated to
      recombinant antibody fragments. Site-specific conjugation of DOTA-peptides to a
      Cys-diabody.
AB  - Arano and co-workers (Arano et al. (1999) Cancer Res. 59, 128-134) have
      synthesized peptides with an N-terminal radioiodinated hippuric acid and a C
      terminal lysine linked to antibody fragments via the epsilon-amino group of
      lysine that show reduced kidney uptake compared to antibody fragments directly
      radioiodinated. This approach takes advantage of the lysine specific
      carboxypeptidase activity of the kidney brush border enzymes that cleave off the
      radiolabeled peptide linker from the antibody fragment prior to uptake by
      proximal tubule cells. On the basis of their approach, we have synthesized a
      tetrapeptide with an N-terminal DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetic acid) and a C-terminal (N(epsilon)-maleoyl)lysine that was site
      specifically conjugated to an anti-CEA diabody (Yazaki et al. (2001) Bioconjugate
      Chem. 12, 220-228) that was engineered to contain a C-terminal cysteine (Cys
      diabody). Biodistributions of the In-111-radiolabeled conjugate in nude mice show
      significantly reduced kidney uptake (a maximum of 82%ID/g at 6 h) compared to In
      111 radiolabeled DOTA-diabody (184%ID/g at 6 h) in which DOTA was conjugated to
      endogenous lysine residues using DOTA-active ester chemistry. To further reduce
      kidney uptake, a homologous compound with a C-terminal (N(epsilon)-amino-1,6
      hexane-bis-vinyl sulfone)lysine was synthesized and site-specifically conjugated
      to the Cys-diabody. Biodistributions of this In-111-labeled conjugate reduced
      kidney uptake to 54%ID/g at 6 h. To explore the effect of the relative positions
      of the chelate vs the cys-diabody on kidney uptake, we also synthesized a
      tetrapeptide with an N-terminal bromoacetate for conjugation to Cys-diabody and a
      C-terminal (N(epsilon)-amidino-propyl-3-thio-vinylsulfonyl-DO3A)lysine. This
      peptide essentially reverses the positions of the chelate and Cys-diabody
      attachment points on the peptide, while retaining the linker length on the
      epsilon-amino group of the lysine. In this case, biodistributions of the In-111
      radiolabeled conjugate in nude mice showed high kidney uptake (189%ID/g at 6 h),
      comparable to that obtained with the In-111-radiolabeled active ester conjugated
      DOTA-diabody (184%ID/g at 6 h). We conclude that the peptide linker strategy of
      Arano and co-workers to reduce kidney uptake can be successfully applied to
      chelate/radiometal complexes and requires that the chelate/radiometal be located
      at the N-terminus of the peptide and the antibody fragment attachment site on the
      epsilon-amino group of the lysine. Furthermore, we demonstrated a role for the
      attachment chemistry to the epsilon-amino group of the lysine on the magnitude of
      kidney uptake.

PMID- 12236781
TI  - A biomimetic pH-responsive polymer directs endosomal release and intracellular
      delivery of an endocytosed antibody complex.
AB  - Poly(propylacrylic acid) (PPAAc) is a synthetic pH-responsive polymer that has
      been shown to disrupt cell membranes at low pH values typical of the endosome,
      but not at physiological pH, suggesting its use as an endosomal-releasing agent
      [Murthy et al. J. Controlled Release 61, 137-43]. We have constructed an antibody
      targeted biotherapeutic model to investigate whether PPAAc can enhance
      intracellular trafficking of proteins to the cytoplasm. A ternary complex
      composed of a biotinylated anti-CD3 antibody, streptavidin, and biotinylated
      PPAAc was fluorescently labeled, and its intracellular fate was analyzed by
      confocal microscopy, flow cytometry, and quantitative western blotting of cell
      fractionates. The 64.1 anti-CD3 antibody was previously shown to direct receptor
      mediated endocytosis in the Jurkat T-cell lymphoma cell line and was rapidly
      trafficked from the endosome to the lysosomal compartment. The antibody
      streptavidin complex was also rapidly internalized to the endosomal/lysosomal
      compartment and retained there, as evidenced by punctate regions of fluorescence
      observed by confocal fluorescence microscopy. In samples containing the ternary
      complex of antibody, streptavidin, and PPAAc-biotin, diffuse fluorescence in the
      cytoplasm was observed, indicating that PPAAc enhanced translocation to the
      cytoplasm. This was confirmed by western blotting analysis of the isolated
      cytoplasm. Flow cytometry results demonstrated that neither streptavidin nor
      PPAAc caused nonspecific uptake of the complex, nor did they inhibit antibody
      mediated endocytosis. The striking enhancement of protein delivery to the
      cytoplasm by complexed PPAAc suggests that this polymer could provide a new
      delivery agent for therapeutic, vaccine, and diagnostics development.

PMID- 12236782
TI  - Synthesis of releasable electrophore tags for applications in mass spectrometry.
AB  - Releasable electrophore mass tags (electrophore tags) are compounds for use as
      labels in ligand assays such as hybridization assays and immunoassays. In such
      assays, the electrophore-tagged reagent (e.g., DNA probe or antibody) is
      quantified at the conclusion of the assay by cleaving a bond in the attached tag
      so that the electrophore part can be brought into the gas phase (usually
      thermally) for detection by electron capture mass spectrometry (EC-MS) or a
      related technique. Interest in these tags is promoted mainly by their potential
      to provide highly sensitive and multiplexed assays. The high multiplexing arises
      from the opportunity to measure many such tags simultaneously in the mass
      spectrometer, where each tag has an electrophore part with a unique mass. In this
      study five precursors of electrophore mass tags are presented. Each precursor can
      lead to a large library of electrophore tags in a practical way, since each
      precursor can be converted to many different electrophore tags by reaction with
      commonly available phenols that provide a variation in mass. The phenol-reactive
      part of the tag is either a polyfluorobiphenyl or a benzyl chloride moiety.
      Representative library compounds are prepared and detected in an inert ester form
      by gas chromatography electron capture mass spectrometry (GC-EC-MS). Further, one
      tag is conjugated to DNA, and the resulting product is detected by laser-induced
      electron capture time-of-flight mass spectrometry on a silver surface. A
      calculation by the semiempirical method AM1 for an ion formed by one of the
      electrophores suggests that ring rotation promotes dissociative electron capture.
      The features of practical synthesis, simple composition, physicochemical
      stability, high multiplicity, high sensitivity, and potential for high throughput
      detection make releasable electrophore mass tags attractive for highly
      multiplexed assays. This includes their use in SNP assays or dideoxy DNA
      sequencing for detection of mutations in individuals, where the combination of
      high accuracy and speed is essential.

PMID- 12236783
TI  - Acridine conjugates of 3-clip-phen: influence of the linker on the synthesis and
      the DNA cleavage activity of their copper complexes.
AB  - To increase the DNA cleavage activity and the cell delivery of the
      bis(phenanthroline) DNA cleaver "3-Clip-Phen", conjugates between 3-Clip-Phen and
      the intercalators acridine and 6-chloro-2-methoxyacridine, through amino acid
      linkers of various length, were prepared. After complexation with CuCl(2), the
      ability of these conjugates to cleave phiX 174 DNA in the presence of a reductant
      and air was compared. The results indicated that (i) the coupling of 3-Clip-Phen
      to an acridine derivative increased the DNA cleavage efficiency of the copper
      complexes, (ii) the acridine derivatives were more active than 6-chloro-2
      methoxyacridine derivatives, (iii) the linker length influenced cleavage
      efficiency, the highest DNA cleavage activity being obtained for an aminocaproic
      spacer.

PMID- 12236784
TI  - Improvement of pharmacokinetics of radioiodinated Tyr(3)-octreotide by
      conjugation with carbohydrates.
AB  - Among a variety of other factors, the clearance kinetics and routes of excretion
      of radiopharmaceuticals are of crucial importance for early and high
      tumor/background ratios and thus signal intensity in diagnostic imaging by single
      photon emission tomography (SPECT) or positron emission tomography (PET). To
      overcome the unfavorable pharmacokinetics of radiohalogenated octreotide
      analogues, we evaluated three carbohydrated conjugates of Tyr(3)-octreotide
      (TOC). Glucose ([(125)I]Gluc-TOC), maltose ([(125)I]Malt-TOC), and maltotriose
      ([(125)I]Mtr-TOC) derivatives of [(125)I]TOC were synthesized via Maillard
      reaction and subsequent radioiodination. In cells transfected with sst1-sst5, I
      Malt-TOC, and I-Mtr-TOC show sst-subtype binding profiles similar to I-TOC with
      high affinity for sst2. Comparative biodistribution studies 10, 30, and 60 min pi
      in nude mice bearing rat pancreatic tumor xenografts showed fast blood clearance
      for all glycosylated derivatives. Due to their markedly increased hydrophilicity,
      [(125)I]Gluc-TOC and [(125)I]Malt-TOC were mainly cleared via the kidneys, which
      led to a significant decrease in activity accumulation in liver and intestine
      (5.3 and 1.4 versus 10.6%ID/g for [(125)I]TOC in the liver, 1.7 and 1.0 versus
      3.8%ID/g for [(125)I]TOC in the intestine 60 min pi). For all compounds,
      hydrophilicity and uptake in liver and intestines correlate. Uptake of the
      carbohydrate conjugates in the kidney was comparable. Compared to the parent
      compound, the accumulation of the carbohydrated compounds in sst-rich tissues
      (pancreas, adrenals) was increased by a factor of 1.5-3.5. While tumor uptake of
      [(125)I]TOC (6.7 +/- 2.6%ID/g), [(125)I]Malt-TOC (5.3 +/- 1.9%ID/g), and
      [(125)I]Mtr-TOC (4.9 +/- 2.2%ID/g) at 30 min postinjection was comparable,
      accumulation of [(125)I]Gluc-TOC was significantly increased (10.1 +/- 2.8%ID/g
      at 30 min pi). Somatostatin receptor specificity of tumor uptake was confirmed by
      pretreatment, competition, and displacement experiments in vivo using 0.8 mg
      TOC/kg and gamma-camera imaging. Glycosylation proved to be a powerful tool for
      the development of high affinity sst ligands with excellent excretion profiles
      and improved tumor accumulation.

PMID- 12236785
TI  - Pegylated zinc protoporphyrin: a water-soluble heme oxygenase inhibitor with
      tumor-targeting capacity.
AB  - Heme oxygenase (HO) is a key enzyme in heme metabolism; it oxidatively degrades
      heme to biliverdin, accompanied by formation of free iron and carbon monoxide.
      Biliverdin is subsequently reduced by cytosolic biliverdin reductase to form
      bilirubin, a potent antioxidant. We recently found that tumor cells utilize HO to
      protect themselves from oxidative stress by producing the antioxidant bilirubin.
      This result suggested an important potential therapeutic strategy: suppression of
      bilirubin production with the use of HO inhibitors; hence, cancer cells become
      vulnerable to oxidative stress induced by anticancer drugs or leukocytes of the
      host. This concept was validated by using the intraarterial administration of an
      HO inhibitor, zinc protoporphyrin, in nonphysiological solution. In the present
      study, zinc protoporphyrin (ZnPP) was conjugated with poly(ethylene glycol) (PEG)
      with molecular weight of 5000, to make ZnPP, a water-soluble compound (PEG-ZnPP),
      and to improve its tumor-targeting efficiency. PEG was conjugated to ZnPP through
      newly introduced amino groups, where ethylenediamine residues were added at C6
      and C7 of protoporphyrin. The divalent zinc cation was chelated into the
      protoporphyrin ring to obtain PEG-ZnPP. PEG-ZnPP did become highly water-soluble,
      and it formed multimolecular associations with molecules larger than 70 kDa in
      aqueous media. PEG-ZnPP inhibited splenic microsomal HO activity in vitro in a
      competitive manner in the presence of hemin, with an apparent inhibitory constant
      of 0.12 microM. Most important, PEG-ZnPP injected intravenously significantly
      suppressed intratumor HO activity in a murine solid tumor model, which suggests
      that tumor-targeted inhibition of HO is possible with the use of PEG-ZnPP.

PMID- 12236786
TI  - Specific labeling of polypeptides at amino-terminal cysteine residues using Cy5
      benzyl thioester.
AB  - Even for moderately sized proteins, the multiple occurrence of cysteine and
      lysine residues often prevents the specific labeling of polypeptides with a
      single probe. To increase specificity, a method was developed to convert the
      commonly available succinimidyl esters of fluorescent dyes into benzyl thioesters
      via trimethyl aluminum-activated benzyl mercaptan. The thioester can then be
      reacted very specifically with polypeptides containing an N-terminal cysteine
      residue, forming a stable amide bond, analogous to the native chemical ligation
      of peptide fragments. Both reaction steps are easy to perform and proceed to high
      yields. The practicability of the approach was demonstrated using the popular
      cyanine dye Cy5 and a soluble peptide, and it is expected to be applicable to a
      wide range of succinimidyl esters and both chemically and recombinantly
      synthesized proteins. The method should dramatically facilitate the preparation
      of proteins for experiments requiring exact positioning of labels, for instance,
      Forster resonance energy transfer studies.

PMID- 12236787
TI  - Incorporation of reversibly cross-linked polyplexes into LPDII vectors for gene
      delivery.
AB  - LPDII vectors are synthetic vehicles for gene delivery composed of polycation
      condensed DNA complexed with anionic liposomes. In this study, we evaluated the
      stability and transfection properties of polyethylenimine (PEI, 25 kDa)/DNA
      polyplexes before and after covalent cross-linking with
      dithiobis(succinimidylpropionate) (DSP) or dimethyl x 3,3'
      dithiobispropionimidate x 2HCl (DTBP), either alone or as a component of LPDII
      vectors. We found that cross-linking PEI/DNA polyplexes at molar ratios > or
      =10:1 (DSP or DTBP:PEI) stabilized these complexes against polyanion disruption,
      and that this effect was reversible by reduction with 20 mM dithioerythritol
      (DTE). Transfection studies with polyplexes cross-linked at molar ratios of 10:1
      100:1 in KB cells, a folate receptor-positive oral carcinoma cell line, showed
      decreasing luciferase gene expression with increasing cross-linking ratio.
      Subsequently, polyplexes, cross-linked with DSP at a molar ratio of 10:1, were
      combined with anionic liposomes composed of diolein/cholesteryl hemisuccinate
      (CHEMS) (6:4 mol/mol), diolein/CHEMS/poly(ethylene glycol)
      distearoylphosphatidylethanolamine (PEG-DSPE) (6:4:0.05 mol/mol), or
      diolein/CHEMS/folate-PEG-cholesterol (folate-PEG-Chol) (6:4:0.05 mol/mol) for
      LPDII formation. Transfection studies in KB cells showed that LPDII vectors
      containing cross-linked polyplexes mediated approximately 2-15-fold lower gene
      expression than LPDII prepared with un-cross-linked polyplexes, depending on the
      lipid:DNA ratio. Inclusion of PEG-DSPE at 0.5 mol % appeared to further decrease
      transfection levels approximately 2-5-fold. Compared with LPDII formulated with
      PEG-DSPE, LPDII incorporating 0.5 mol % folate-PEG-Chol exhibited higher
      luciferase activities at all lipid:DNA ratios tested, achieving an approximately
      10-fold increase at a lipid:DNA ratio of 5. Compared with cross-linked LPDII
      vectors without PEG-DSPE, inclusion of folate-PEG-Chol increased luciferase
      activities 3-4-fold between lipid:DNA ratios of 1 and 5. Interestingly, inclusion
      of 1 mM free folate in the growth media during transfection increased
      transfection activity approximately 3-4-fold for cross-linked LPDII vectors and
      LPDII containing folate-PEG-Chol, but had no effect on the transfection activity
      of LPDII formulated with PEG-DSPE. However, in the presence of 5 mM free folate,
      the luciferase activity mediated by LPDII vectors containing folate-PEG-Chol was
      reduced approximately 6-fold. Transmission electron micrographs were also
      obtained to provide evidence of LPDII complex formation. Results showed that
      cross-linked LPDII vectors appear as roughly spherical aggregated complexes with
      a rather broad size distribution ranging between 300 and 800 nm.

PMID- 12236788
TI  - Pretargeting for cancer radioimmunotherapy with bispecific antibodies: role of
      the bispecific antibody's valency for the tumor target antigen.
AB  - The use of a divalent effector molecule improves bispecific antibody (bsMAb)
      pretargeting by enabling the cross-linking of monovalently bound bsMAb on the
      cell surface, thereby increasing the functional affinity of a bsMAb. In this
      work, it was determined if a bsMAb with divalency for the primary target antigen
      would improve bsMAb pretargeting of a divalent hapten. The pretargeting of a
      (99m)Tc-labeled divalent DTPA-peptide, IMP-192, using a bsMAb prepared by
      chemically coupling two Fab' fragments, one with monovalent specificity to the
      primary target antigen, carcinoembryonic antigen (CEA), and to indium-loaded DTPA
      [DTPA(In)], was compared to two other bsMAbs, both with divalency to CEA. One
      conjugate used the whole anti-CEA IgG, while the other used the anti-CEA
      F(ab')(2) fragment to make bsMAbs that had divalency to CEA, but with different
      molecular weights to affect their pharmacokinetic behavior. The rate of bsMAb
      blood clearance was a function of molecular weight (IgG x Fab' < F(ab')(2) x Fab'
      < Fab' x Fab' conjugate). The IgG x Fab' bsMAb conjugate had the highest uptake
      and longest retention in the tumor. However, when used for pretargeting, the
      F(ab')(2) x Fab' conjugate allowed for superior tumor accretion of the (99m)Tc
      IMP-192 peptide, because its more rapid clearance from the blood enabled early
      intervention with the radiolabeled peptide when tumor uptake of the bsMAb was at
      its peak. Excellent peptide targeting was also seen with the Fab' x Fab'
      conjugate, albeit tumor uptake was lower than with the F(ab')(2) x Fab'
      conjugate. Because the IgG x Fab' bsMAb cleared from the blood so slowly, when
      the peptide was given at the time of its maximum tumor accretion, the peptide was
      captured predominantly by the bsMAb in the blood. Several strategies were
      explored to reduce the IgG x Fab' bsMAb remaining in the blood to take advantage
      of its 3-4-fold higher tumor accretion than the other bsMAb conjugates. A number
      of agents were tested, including those that could clear the bsMAb from the blood
      (e.g., galactosylated or nongalactosylated anti-id antibody) and those that could
      block the anti-DTPA(In) binding arm [e.g., DTPA(In), divalent-DTPA(In) peptide,
      and DTPA coupled to bovine serum albumin (BSA) or IgG]. When clearing agents were
      given 65 h after the IgG x Fab' conjugate (time of maximum tumor accretion for
      this bsMAb), (99m)Tc-IMP-192 levels in the blood were significantly reduced, but
      a majority of the peptide localized in the liver. Increasing the interval between
      the clearing agent and the time the peptide was given to allow for further
      processing of the bsMAb-clearing agent complex did not improve targeting. At the
      dose and level of substitution tested, galacosylated BSA-DTPA(In) was cleared too
      quickly to be an effective blocking agent, but BSA- and IgG-DTPA(In) conjugates
      were able to reduce the uptake of the (99m)Tc-IMP-192 in the blood and liver.
      Tumor/nontumor ratios compared favorably for the radiolabeled peptide using the
      IgG x Fab'/blocking agent combination and the F(ab')(2) x Fab' (no
      clearing/blocking agent), and peptide uptake 3 h after the blocking agent even
      exceeded that of the F(ab')(2) x Fab'. However, this higher level of peptide in
      the tumor was not sustained over 24 h, and actually decreased to levels lower
      than that seen with the F(ab')(2) x Fab' by this time. These results demonstrate
      that divalency of a bsMAb to its primary target antigen can lead to higher tumor
      accretion by a pretargeted divalent peptide, but that the pharmacokinetic
      behavior of the bsMAb also needs to be optimized to allow for its clearance from
      the blood. Otherwise, blocking agents will need to be developed to reduce
      unwanted peptide uptake in normal tissues.

PMID- 12236789
TI  - Synthesis of N-acetyl-D-galactosamine and folic acid conjugated ribozymes.
AB  - To evaluate potential improvement in tissue specific targeting and cellular
      uptake of therapeutic ribozymes, we have developed three new phosphoramidite
      reagents. These reagents can be used in automated solid-phase synthesis to
      produce oligonucleotide conjugates containing N-acetyl-D-galactosamine (targeting
      hepatocytes) and folic acid (targeting tumor). N-Acetyl-D-galactosamine was
      attached through a linker to both 2'-amino-2'-deoxyuridine and D-threoninol
      scaffolds, and these conjugates were converted to phosphoramidite building
      blocks. Incorporation of a D-threoninol-based monomer into ribozymes provided
      multiply labeled ribozyme conjugates. Attachment of the fully protected pteroic
      acid to the D-threoninol-6-aminocaproyl-L-glutamic acid construct afforded the
      folic acid conjugate, which was converted into the phosphoramidite and
      incorporated onto the 5'-end of the ribozyme.

PMID- 12236790
TI  - Trifunctional conjugation reagents. Reagents that contain a biotin and a
      radiometal chelation moiety for application to extracorporeal affinity adsorption
      of radiolabeled antibodies.
AB  - A method of removing radiolabeled monoclonal antibodies (mAbs) from blood using a
      device external to the body, termed extracorporeal affinity-adsorption (EAA), is
      being evaluated as a means of decreasing irradiation of noncancerous tissues in
      therapy protocols. The EAA device uses an avidin column to capture biotinylated
      radiolabeled mAbs from circulated blood. In this investigation, three
      trifunctional reagents have been developed to minimize the potential deleterious
      effect on antigen binding brought about by the combination of radiolabeling and
      biotinylation of mAbs required in the EAA approach. The studies focused on
      radiolabeling with (111)In and (90)Y, so the chelates CHX-A' '-DTPA and DOTA,
      which form stable attachments to these radionuclides, were incorporated in the
      trifunctional reagents. The first trifunctional reagent prepared did not
      incorporate a group to block the biotin cleaving enzyme biotinidase, but the two
      subsequent reagents coupled aspartic acid to the biotin carboxylate for that
      purpose. All three reagents used 4,7,10-trioxa-1,13-tridecanediamine as water
      soluble spacers between an aminoisophthalate core and the biotin or chelation
      group. The mAb conjugates were radioiodinated to evaluate cell binding as a
      function of substitution. Radioiodination was used so that a direct comparison
      with unmodified mAb could be made. Evaluation of the number of conjugates per
      antibody versus cell binding immunoreactivities indicated that minimizing the
      number of conjugates was best. Interestingly, a decrease of radioiodination yield
      as a function of the number of isothiocyanate containing conjugates per mAb was
      noted. The decreased yields were presumably due to the presence of thiourea
      functionality formed in the conjugation reaction. Radiolabeling with (111)In and
      (90)Y was facile at room temperature for conjugates containing the CHX-A' ', but
      elevated temperature (e.g., 45 degrees C) was required to obtain good yields with
      the DOTA chelate. Stability of (90)Y labeled mAb in serum, and when challenged
      with 10 mM EDTA, was high. However, challenging the (90)Y labeled mAb with 10 mM
      DTPA demonstrated high stability for the DOTA containing conjugate, but low
      stability for the CHX-A' ' containing conjugate. Thus, the choice between these
      two chelating moieties might be made on requirements for facile and gentle
      labeling versus very high in vivo stability. Application of the trifunctional
      biotinylation reagents to the blood clearance of labeled antibodies in EAA is
      under investigation. The new reagents may also be useful for other applications.

PMID- 12236791
TI  - A novel 2'-(N-methylpyridinium acetate) prodrug of paclitaxel induces superior
      antitumor responses in preclinical cancer models.
AB  - The development of novel strategies for the treatment of malignancies by
      successful intervention in advanced stage disease is a major challenge in
      oncology. We tested the hypothesis that this can be achieved by the rational
      design of taxoid onium salts modified at C-7 and C-2' positions. The
      characterization of these molecules revealed a dramatically improved water
      solubility and prodrug behavior in plasma. Specifically, all compounds released
      parental paclitaxel with half-lives ranging from 0.9 to 180 min. In the absence
      of plasma, only the 2'-(N-methylpyridinium acetate) derivative of paclitaxel (2'
      MPA-paclitaxel) revealed a complete abrogation of paclitaxel specific microtubule
      assembly disassembly dynamics and a 3 log reduction in cellular binding,
      indicating that reversible blockage of the C-2' position by methylpyridinium
      acetate yields a true paclitaxel prodrug. Structure/activity profiles of all
      compounds in tissue culture revealed cytotoxicity effective at picomolar
      concentrations with a panel of 16 cancer cell lines in contrast to 4 nonmalignant
      cell lines. Importantly, the decisive cytotoxic potential observed in vitro for
      all compounds correlated only with in vivo findings for 2'-MPA-paclitaxel.
      Specifically, the 2'-MPA-paclitaxel prodrug induced regression of primary tumors
      in three xenograft models of nonsmall cell lung carcinoma, ovarian carcinoma and
      prostate cancer, in contrast to ineffective C-7 derivatives and parental
      paclitaxel. At the same time, a reduced systemic toxicity of 2'-MPA-paclitaxel
      was observed in contrast to a far more toxic parental paclitaxel. Taken together,
      these findings demonstrate that the 2'-MPA-paclitaxel prodrug is a promising new
      candidate for cancer therapy.

PMID- 12236793
TI  - Chemical synthesis and characterization of conjugates of a novel catechol-O
      methyltransferase inhibitor.
AB  - BIA 3-202, 1-(3,4-dihydroxy-5-nitrophenyl)-2-phenylethanone 3, is a novel,
      reversible, and tight-binding peripheral inhibitor of the enzyme catechol-O
      methyltransferase (COMT), which is currently under clinical evaluation for the
      treatment of Parkinson's disease as an adjunct to current L-Dopa/peripheral
      decarboxylase inhibitor therapy. Chemically pure, well-characterized reference
      standards of conjugates of 3 were required for investigation of the routes of
      metabolism in several animal species (including humans) and for pharmacokinetic
      studies. The lack of suitable literature precedents for efficient, regioselective
      synthesis of nitrocatechol conjugate metabolites prompted us to develop efficient
      and highly selective chemical preparations of O-glucuronide and O-sulfate
      conjugates of 3 such that multigram quantities of excellent purity can now be
      conveniently synthesized. It is anticipated that these procedures could be
      applied to the synthesis of conjugates of other COMT inhibitors, also based on
      the 3-nitrocatechol pharmacophore.

PMID- 12236792
TI  - Functionalized congeners of tyrosine-based P2X(7) receptor antagonists: probing
      multiple sites for linking and dimerization.
AB  - Chemically funtionalized analogues of antagonists of the P2X(7) receptor, an ATP
      gated cation channel, were synthesized as tools for biophysical studies of the
      receptor. These functionalized congeners were intended for use in chemical
      conjugation with retention of biological potency. The antagonists were L-tyrosine
      derivatives, related to [N-benzyloxycarbonyl-O-(4-arylsulfonyl)-L
      tyrosyl]benzoylpiperazine (such as MRS2409, 2). The analogues were demonstrated
      to be antagonists in an assay of human P2X(7) receptor function, consisting of
      inhibition of ATP-induced K(+) efflux in HEK293 cells expressing the recombinant
      receptor. The analogues were of the general structure R(1)-Tyr(OR(2))-piperazinyl
      R(3), in which three positions (R(1)-R(3)) were systematically varied in
      structure through introduction of chemically reactive groups. Each of the three
      positions was designed to incorporate a 3- or 4-nitrophenyl group. The nitro
      groups were reduced using NaBH(4)-copper(II) acetylacetonate to amines, which
      were either converted to the isothiocyanate groups, as potential affinity labels
      for the receptor, or acylated, as models for conjugation. An alternate route to
      N(alpha)-3-aminobenzyloxycarbonyl functionalization was devised. The various
      positions of functionalization were compared for effects on biological potency,
      and the R(2) and R(3) positions were found to be most amenable to derivatization
      with retention of high potency. Four dimeric permutations of the antagonists were
      synthesized by coupling each of the isothiocyanate derivatives to either the
      precursor amine or to other amine congeners. Only dimers linked at the R(2)
      position were potent antagonists. In concentration-response studies, two
      derivatives, a 3-nitrobenzyloxycarbonyl derivative 18 and a 4
      nitrotoluenesulfonate 26b, displayed IC(50) values of roughly 100 nM as
      antagonists of P2X(7) receptor-mediated K(+) flux.

PMID- 12236794
TI  - Development of annexin V mutants suitable for labeling with Tc(i)-carbonyl
      complex.
AB  - (99m)Tc-annexin V can be used to image organs undergoing cell death during cancer
      chemotherapy and organ transplant rejection. We investigated whether the novel Tc
      carbonyl labeling method would be suitable for annexin V. Two mutant molecules of
      annexin V, called annexin V-122 and annexin V-123, were constructed with N
      terminal extensions containing either three or six histidine residues. These
      molecules were expressed cytoplasmically in E. coli and purified with a final
      yield of 33 mg of protein/L of culture. Analysis by SDS-PAGE, isoelectric
      focusing, gel filtration chromatography, and mass spectrometry confirmed the
      purity and homogeneity of the protein preparations. Both mutant proteins retained
      full binding affinity for cell membranes with exposed phosphatidylserine. Using
      the Tc-carbonyl reagent, both proteins could be labeled with (99m)Tc to specific
      activities of at least 10-20 microCi/microg with full retention of bioactivity.
      The radiolabeled proteins were stable when incubated with phosphate-buffered
      saline or serum in vitro, and there was no transchelation of label to serum
      proteins during in vitro incubation. In conclusion, annexin V can be modified
      near its N-terminus to incorporate sequences that form specific chelation sites
      for (99m)Tc-carbonyl without altering its high affinity for cell membranes.

PMID- 12236795
TI  - Copolymers of ethylene imine and N-(2-hydroxyethyl)-ethylene imine as tools to
      study effects of polymer structure on physicochemical and biological properties
      of DNA complexes.
AB  - A series of five poly[(ethylene imine)-co-N-(2-hydroxyethyl-ethylene imine)]
      copolymers with similar molecular weights and different degrees of branching was
      established to study structure-function relationship with regard to
      physicochemical and biological properties as gene delivery systems. Copolymers
      were synthesized by acid-catalyzed ring-opening copolymerization of aziridine and
      N-(2-hydroxyethyl)-aziridine in aqueous solution and characterized by GPC-MALLS,
      (1)H- and (13)C NMR, IR, potentiometric titration, and ion exchange
      chromatography. Complexation of DNA was determined by agarose gel
      electrophoresis, and complex sizes were quantitated by PCS. Cytotoxicity of the
      copolymers in fibroblasts was assessed by MTT-assay, LDH-assay, and hemolysis.
      The transfection efficiency was determined using the reporter plasmid pGL3 in 3T3
      mouse fibroblasts. The copolymers obtained by solution polymerization had
      relatively low molecular weights of about 2000 Da, and the degree of branching
      increased with increasing ethylene imine ratio. The pK(a) as well as the buffer
      capacity increased proportional to the number of primary and secondary amines.
      Higher branched polymers showed stronger complexation and condensation of DNA,
      formed smaller polymer/DNA complexes, and induced the expression of plasmids to a
      higher extent than less branched polymers. In vitro cytotoxic effects and the
      hemolysis of erythrocytes decreased with decreased branching. Our results
      indicate that the basicity and degree of protonation of the polymers depending on
      their amount of primary and secondary amines seem to be important factors both
      for their transfection efficiency and for their cytotoxicity in gene transfer.

PMID- 12236796
TI  - Coupling of a targeting peptide to plasmid DNA using a new type of padlock
      oligonucleotide.
AB  - We have recently described a new method for attaching padlock oligonucleotides to
      supercoiled plasmid DNA at specific sequences. A variant of this method has been
      developed in order to allow the coupling of targeting moieties to plasmids using
      a convenient strategy. After sequence-specific winding around the double-stranded
      target DNA sequence by ligand-induced triple helix formation, the extremities of
      a triplex-forming oligonucleotide hybridize to each other, leaving a dangling
      single-stranded sequence, which is then ligated to a hairpin oligonucleotide
      using T4 DNA ligase. Any targeting moiety may be attached to the hairpin
      oligonucleotide. This strategy was used to attach an NLS peptide to a luciferase
      expressing plasmid. Despite the presence of the padlock oligonucleotide, the
      reporter gene was efficiently expressed after transfection of the plasmid in HeLa
      or T24 cells, using either cationic lipids or cationic polymers as transfecting
      agents. However, no increase in gene expression could be observed as a result of
      peptide attachment. Nevertheless, the coupling strategy described in this paper
      may find applications as a tool for plasmid functionalization in other targeting
      experiments, and may lead to the development of improved vectors for gene
      therapy.

PMID- 12236797
TI  - A trithiolate tripodal bifunctional ligand for the radiolabeling of peptides with
      gallium(III).
AB  - A tripodal bifunctional chelator for gallium has been prepared with a chelation
      core consisting of three thiols and a tertiary amine. The synthesis proceeds in
      13 steps with an overall yield of 22%. An aromatic amine is available for
      conjugation to peptides through carbodiimide coupling. Gallium(III) complexes
      were readily prepared from both the bifunctional chelator and a phenylalanine
      conjugated system. These complexes underwent stability evaluation and were found
      to be stable to ligand exchange and enzymatic hydrolysis. This bifunctional
      chelator appears to be suitable for conjugation to peptides for the preparation
      of gallium radiopharmaceuticals.

PMID- 12236798
TI  - New reagents and methods for the synthesis of internal and 3'-labeled DNA.
AB  - The syntheses of two new nucleoside phosphoramidites containing a hydroxyl
      functionality masked by a levulinate protecting group are presented; N(4)-(2
      (ethylene glycol-2-levulinate)ethyl)-5-methyl-5'-(4,4'-dimethoxytrityl)-3'-O-(2
      cyanoethyldiisopropylphosphoramidite)-2'-deoxycytidine 1 and 5-(N-(6-O-levulinoyl
      1-aminohexyl)-3(E)-acrylamido)-5'-(4,4'-dimethoxytrityl)-3'-(2
      cyanoethyldiisopropylphosphoramidite)-2'-deoxyuridine 3. Optimization of solid
      phase-supported synthetic parameters for incorporation of these into DNA, removal
      of the levulinate group by exposure to dilute hydrazine, and subsequent
      attachment of dye labels is described. Synthesis of the known compound 5-(N-(6
      trifluoroacetylaminohexyl)-3(E)-acrylamido)-5'-(4,4'-dimethoxytrityl)-3'-(2
      cyanoethyldiisopropylphosphoramidite)-2'-deoxyuridine 2 (1), containing a masked
      amine at the end of an alkyl chain attached at the 5 position, was also revisited
      using new techniques developed for 3.

PMID- 12236799
TI  - Evaluation of new linkers and synthetic methods for internal modified
      oligonucleotides.
AB  - Several fluorescence resonance energy transfer (FRET) oligonucleotide probes were
      made with different internal linkages between the DNA and the quencher dye. In
      one example, a 5'-fluorescein beta-actin-based 26-mer DNA sequence was
      synthesized bearing an internal Tamra quencher. Two different versions were
      prepared using either conventional C5 [N-(6-aminohexyl)-3-acrylamido]pyrimidine
      modified uridine and solution-phase Tamra active ester coupling or solid-phase
      addition of a Tamra amidite to a C5 [N-(6-hydroxyhexyl)-3-acrylamido]pyrimidine
      modified uridine. The products were compared in functional assays. They performed
      very similarly both in a fluorescence-based melting point assay as well as in
      quantitative PCR. Another set of beta-actin probes were synthesized utilizing N4
      [N-2-(ethylene glycol ethyl)-5-methyl]cytidine and solid-phase Tamra amidite
      addition at positions flanking those of the uridine. These versions gave lower
      T(m)s than either uridine-labeled probe and did not work as well in quantitative
      PCR. A control experiment using oligonucleotides with the same modified residues
      but without fluorophores attached revealed the same trend as the T(m) study of
      internal Tamra-labeled probes. Experimental details for the synthesis,
      purification, and testing are presented.

PMID- 12236800
TI  - A convenient method for the synthesis of amine-terminated poly(ethylene oxide)
      and poly(epsilon-caprolactone).
AB  - A convenient synthetic route to prepare amine-terminated poly(ethylene oxide)
      (PEO) and poly(epsilon-caprolactone) (PCL) was described. The strategy involved
      two-step reactions, the condensation of hydroxyl-terminated PEO and PCL with N
      benzyloxycarbonyl amino acid followed by the catalytic hydrogenation under mild
      conditions. NMR and GPC measurements indicated that the reactions proceeded
      nearly quantitatively. Amine-terminated PEO thus prepared was used to initiate
      the polymerization of alpha-(N(epsilon)-benzyloxycarbonyl-L-lysine) N-carboxy
      anhydride [lys(Z)-NCA], and the results confirmed that the reactivity of the
      amino group was high.

PMID- 12236801
TI  - A general strategy for site-specific double labeling of globular proteins for
      kinetic FRET studies.
AB  - Site-directed mutagenesis provides a straightforward means of creating specific
      targets for chemical modifications of proteins. This capability enhanced the
      applications of spectroscopic methods adapted for addressing specific structural
      questions such as the characterization of partially folded and transient
      intermediate structures of globular proteins. Some applications such as the
      steady state or time-resolved fluorescence resonance energy transfer (FRET)
      detection of the kinetics of protein folding require relatively large quantities
      (approximately 10-100 mg) of site-specific doubly labeled protein samples.
      Engineered cysteine residues are common targets for labeling of proteins. The
      challenge here is to develop methods for selective modification of one of two
      reactive sulfhydryl groups in a protein molecule. A general systematic procedure
      for selective labeling of each of two cysteine residues in a protein molecule was
      developed, using Escherichia coli adenylate kinase (AKe) as a model protein.
      Potential sites for insertion of cysteine residues were selected by examination
      of the crystal structure of the protein. A series of single-cysteine mutants was
      prepared, and the rates of the reaction of each engineered cysteine residue with
      a reference reagent [5,5'-dithiobis(2-nitrobenzoic acid) (DTNB)] were determined.
      Two-cysteine mutants were prepared by selection of pairs of sites for which the
      ratio of this reaction rate constant was high (>80). The conditions for the
      selective labeling reaction were optimized. In a first cycle of labeling, the
      more reactive cysteine residue was labeled with a fluorescent probe (donor). The
      second probe was attached to the less reactive site under unfolding conditions in
      the second cycle of labeling. The doubly and singly labeled mutants retained full
      enzymatic activity and the capacity for a reversible folding-unfolding
      transition. High yields (70-90%) of the preparation of the pure, site-specific
      doubly labeled AK mutant were obtained. The procedure described herein is a
      general outline of procedures, which can meet the double challenge of both site
      specificity and large-scale preparation of doubly labeled proteins.

PMID- 12236803
TI  - Long term cost-of-illness in stroke: an international review.
AB  - An international review of the costs of stroke was conducted to explore data
      sources, and cost variables as well as to compare estimates of the annual
      aggregated cost (prevalence-based) and total per patient long-term cost
      (incidence-based) of care. Dutch, English, French, German, Italian and Spanish
      literature was searched using the keywords stroke, ischaemic stroke, haemorrhagic
      stroke, cerebrovascular accident, cerebral infarction, cost(s), economics, and
      cost analysis. Criteria for study inclusion were: provides estimates of direct
      and/or indirect costs of stroke, published after 1989, methods described in
      adequate detail, and for studies of long-term costs, estimates based on a minimum
      5 years of care following the event. Cost estimates are presented in original
      currencies and US dollars. Among studies representing Australia, New Zealand,
      Western Europe and North America, six prevalence studies reported total annual
      aggregated costs of US dollars 7,975 (1988 values) to US dollars 54,546 (1993
      values) per patient; eight incidence-based studies reported total long-term per
      patient costs of US dollars 18,538 (1991 values) to US dollars 228,038 (1990
      values). Identifiable factors underlying variation included: perspective
      employed, cost variables considered, and exclusion of comorbidities. Although
      lack of uniformity hampers inter-study comparisons, it is evident that stroke
      poses a significant economic burden. Consensus on standard cost variables and
      methods for projections of resource use and survival over time are clearly
      warranted.

PMID- 12236804
TI  - Cost-effectiveness comparison of tizanidine and baclofen in the management of
      spasticity.
AB  - OBJECTIVE: Baclofen and tizanidine are both used for the treatment of muscle
      spasticity of spinal origin. Their effectiveness, cost and adverse-effect
      profiles differ. This paper sets out to estimate the cost effectiveness of each
      drug, and the impact of changing from baclofen to tizanidine. DESIGN: A
      simplified but realistic model of physician behaviour and patient response was
      developed as a decision tree and populated with data derived from the available
      published clinical comparative trials. We considered patients with spasticity
      caused by multiple sclerosis or spinal cord injury. The outcome measure used was
      'cost per successfully treated day' (STD). Costs were estimated from the
      perspective of the UK National Health Service at 2000 values. RESULTS: Expected
      cost for a cohort of 100 patients over 1 year was estimated to be pound 181 545
      with baclofen and pound 211 930 with tizanidine. The estimated number of STDs was
      20,192 with tizanidine and 17,289 with baclofen. The overall cost effectiveness
      of managing spasticity using baclofen and tizanidine was very similar ( pound
      10.50 and pound 10.49 per STD respectively). The incremental cost effectiveness
      (ICE) of using tinzanidine as an alternative to baclofen for first-line treatment
      was pound 10.47 per STD. Sensitivity analysis found the model to be robust to
      changes in key parameters CONCLUSION: Drug cost should not be a determining
      factor in making this treatment choice, as the cost effectiveness ratios are
      similar for both products.

PMID- 12236802
TI  - Vision-specific instruments for the assessment of health-related quality of life
      and visual functioning: a literature review.
AB  - Clinically objective measures such as visual acuity or visual field provide an
      assessment of a patient's visual status. However such measures may not reflect
      the degree of visual impairment the patient experiences in his or her daily
      activities. Visual impairment has been shown to have negative effects on health
      related quality of life (HR-QOL) and a significant impact on daily functioning,
      including social activities. As such, there is a growing recognition of the
      importance of patient-reported outcomes of visual functioning. This review
      examines the development and psychometric properties of 22 vision-specific
      instruments assessing visual functioning and/or the impact of visual impairment
      on HR-QOL or daily activities. Issues relevant to assessing vision-specific
      subjective outcomes are reviewed, with specific application of the reviewed
      instruments. Three instruments, the Activities of Daily Vision Scale, National
      Eye Institute Visual Function Questionnaire, and Visual Function Index have been
      well validated and widely used, but others also show promise. To fully capture
      the benefits of a new ophthalmology treatment (or new treatment for eye disease)
      a valid and reliable visual instrument, in which the psychometric performance has
      been demonstrated in the particular ocular condition being treated, should be
      utilised.

PMID- 12236805
TI  - UK department of health guidance on prescribing for impotence following the
      introduction of sildenafil: potential to contain costs in the average health
      authority district.
AB  - OBJECTIVES: To evaluate the effectiveness at containing service costs of the UK's
      Department of Health (DoH) guidance on prescribing for impotence implemented
      after the introduction of sildenafil and taking effect from 1 July 1999. DESIGN:
      A pragmatic economic analysis of the impact of the DoH guidance on specialist
      care activity and costs and primary-care prescribing costs from the perspective
      of the UK National Health Service. Primary-care prescribing costs and specialist
      care activity and cost data were collected for 12-month periods before and after
      the introduction of the guidance. SETTING: Portsmouth and South East Hampshire
      Health Authority. RESULTS: Specialist-care activity and associated costs fell by
      70% in the first year following the introduction of the DoH guidance while
      primary-care prescribing costs doubled. The overall cost for providing impotence
      services in Portsmouth and South East Hampshire in 1999-2000 was pound 232,619,
      and is similar to the cost incurred in 1998-1999 of pound 225,108 (uplifted to
      1999-2000 values). CONCLUSIONS: The DoH guidance on prescribing for impotence has
      effectively reduced specialist-care activity and costs in Portsmouth and South
      East Hampshire. It offers the potential to allow the overall costs of impotence
      services in the district to be contained even with the use of higher cost drugs,
      such as sildenafil.

PMID- 12236806
TI  - Costs and effectiveness of using coumarins before, during and after coronary
      angioplasty.
AB  - BACKGROUND: In the Balloon Angioplasty and Anticoagulation Study (BAAS),
      coumarins added to routine aspirin therapy before coronary angioplasty reduced
      cardiac events at the cost of a slightly higher risk of bleeding complications.
      OBJECTIVE: To determine the cost effectiveness of coumarin treatment, based on
      the occurrence of both cardiac and bleeding events. METHODS: Effectiveness was
      measured, applying two definitions, in terms of the number of events occurring at
      one year. In the first definition, the occurrence of death, myocardial infarction
      (MI), or stroke was assessed. The second definition also included
      revascularisations and major bleeding episodes as an event. Costs were limited to
      direct medical costs. Cost effectiveness was addressed by probability ellipses
      representing the point estimates and uncertainties surrounding both costs and
      effectiveness. RESULTS: At 1 year, death, MI or stroke occurred 1.1% less often
      when treating with aspirin plus coumarins rather than aspirin therapy alone. When
      revascularisations and major bleeding events were also included, the difference
      was 5.0%. Overall, the additional costs in relation to coumarin treatment were
      compensated by a reduction in repeat interventions. When including all costs, the
      savings associated with coumarin treatment were estimated at Euros 235 per
      patient after 1 year. The probability that coumarins are cost saving was
      estimated at 0.85. The probability that coumarins combine additional
      effectiveness with cost savings was estimated at 0.70 when survival free of MI or
      stroke as an effectiveness measure was considered, and at 0.83 when survival free
      of MI, stroke, revascularisation or major bleeding was considered. CONCLUSION:
      Coumarin therapy added to routine aspirin therapy before coronary angioplasty,
      and continued during follow-up, may not only be considered more effective but
      also cost saving relative to aspirin therapy alone.

PMID- 12236807
TI  - Combining a budgetary-impact analysis and a cost-effectiveness analysis using
      decision-analytic modelling techniques.
AB  - BACKGROUND: Reimbursement of new drugs is usually based on the budgetary impact
      of a new drug but there is also increasing demand for cost-effectiveness data on
      new drugs. OBJECTIVE: To present a modelling technique (methodology) for an
      appropriate assessment of the budgetary impact of a new drug, which can
      simultaneously be used for a traditional cost-effectiveness analysis. DESIGN AND
      PERSPECTIVE: To illustrate the methodology, a model was constructed for a new
      hypothetical drug in Parkinson's disease, which allowed us to determine the
      budgetary impact and the cost effectiveness of this new antiparkinsonian drug
      from a societal perspective. The methodology consisted of two steps: (i) a simple
      population model (Markov model) was constructed to validate the epidemiological
      data by proving the consistency between the prevalence and incidence of
      Parkinson's disease for the Dutch population; (ii) this model was extended to a
      more complex model (semi-Markov model) by incorporation of disease progression
      for Parkinson's disease and all relevant economic and clinical measures. These
      included all drug utilisation associated with Parkinson's disease, as well as
      other resource utilisation patterns associated with outpatient and inpatient care
      for the treatment of Parkinson's disease. RESULTS: The study showed that the
      difference in epidemiological data between a simple model and a complex model are
      substantial, which justifies the development of a complex model with a higher
      external validity. The complex model allowed an assessment of all potential
      candidates for the new drug and simultaneously allowed the assessment of the cost
      effectiveness of the new drug versus usual care. CONCLUSION: One model can be
      used for an appropriate assessment of the budgetary impact and the cost
      effectiveness of a new drug.

PMID- 12236808
TI  - 50 years of radiation research: medicine.
AB  - The advances brought about by research in radiation medicine over the past 50
      years are presented. The era began with the atomic explosions in Hiroshima and
      Nagasaki and the establishment of the Atomic Bomb Casualty Commission to
      understand what damage was caused by exposure of a large population to radiation.
      A better understanding of the effects of whole-body exposure led to the
      development of whole-body radiation treatment techniques and to bone marrow
      transplantation in the treatment of leukemias. The field of diagnostic imaging
      was revolutionized by a series of inventions that included angiography,
      mammography, computed tomography, magnetic resonance imaging, magnetic resonance
      spectroscopy, and ultrasound imaging. The field of nuclear medicine came of age
      through new man-made radionuclides and the invention of scanning and imaging
      techniques including positron emission tomography. Radiotherapy, a minor sideline
      of radiology, developed into radiation oncology, an extremely important component
      of modern cancer therapy. The advances in clinical radiotherapy were made
      possible by discoveries and inventions in physics and engineering and by insights
      and discoveries in radiobiology. The result of the last 50 years of progress is a
      very powerful set of clinical tools.

PMID- 12236809
TI  - Dose-response relationship for parathyroid adenoma after exposure to ionizing
      radiation in infancy.
AB  - Several authors have suggested that there is an excess risk of
      hyperparathyroidism, adenomas or hyperplasia after exposure to ionizing
      radiation. There is still, however, some uncertainty about this association,
      because these diseases are often asymptomatic and escape clinical detection if
      not specially searched for. This study is based on a pooled Swedish cohort of
      27,925 persons with skin hemangiomas. The majority received radiation treatment
      in infancy between 1920 and 1965 in Stockholm and Gothenburg. The mean age at
      treatment was 6 months and the median thyroid dose was 0.20 Gy (range 0-28.5 Gy).
      Record linkage with the Swedish Cancer Register for the period 1958-1997 gave 43
      cases of parathyroid adenoma in the cohort. Analyses of excess relative risk
      (ERR) models were performed using Poisson regression methods. Clinical records
      were scrutinized to determine if the childhood radiation exposure was known
      (biased cases) at the time of diagnosis. Seven of the cases of parathyroid
      adenoma were classified as biased cases. The standardized incidence ratio (SIR)
      was 2.10 (95% confidence interval 1.52-2.82) when all cases were included and
      1.76 (95% CI 1.23-2.43) with the biased cases excluded. A linear dose-response
      model with stratification for sex fitted the data best. The ERR per gray was 3.84
      (95% CI 1.56-8.99) with all cases and 1.56 (95% CI 0.36-4.45) with the biased
      cases excluded. There was a significant difference in the ERR per gray between
      the two subcohorts, probably because of different diagnostic activity in the
      regions. Our findings confirm that there is a dose-response relationship for
      radiation-induced parathyroid adenomas.

PMID- 12236810
TI  - Three somatic genetic biomarkers and covariates in radiation-exposed Russian
      cleanup workers of the chernobyl nuclear reactor 6-13 years after exposure.
AB  - Three somatic mutation assays were evaluated in men exposed to low-dose, whole
      body, ionizing radiation. Blood samples were obtained between 1992 and 1999 from
      625 Russian Chernobyl cleanup workers and 182 Russian controls. The assays were
      chromosome translocations in lymphocytes detected by FISH, hypoxanthine
      phosphoribosyltransferase (HPRT) mutant frequency in lymphocytes by cloning, and
      flow cytometic assay for glycophorin A (GPA) variant frequency of both deletion
      (N/O) and recombination (N/N) events detected in erythrocytes. Over 30 exposure
      and lifestyle covariates were available from questionnaires. Among the covariates
      evaluated, some increased (e.g. age, smoking) and others decreased (e.g. date of
      sample) biomarker responses at a magnitude comparable to Chernobyl exposure. When
      adjusted for covariates, exposure at Chernobyl was a statistically significant
      factor for translocation frequency (increase of 30%, 95% CI of 10%-53%, P =
      0.002) and HPRT mutant frequency (increase of 41%, 95% CI of 19%-66%, P < 0.001),
      but not for either GPA assay. The estimated average dose for the cleanup workers
      based on the average increase in translocations was 9.5 cGy. Translocation
      analysis is the preferred biomarker for low-dose radiation dosimetry given its
      sensitivity, relatively few covariates, and dose-response data. Based on this
      estimated dose, the risk of exposure-related cancer is expected to be low.

PMID- 12236811
TI  - Teratogenic effects of mild heat stress during mouse embryogenesis: effect of
      Trp53.
AB  - Hyperthermia can be teratogenic in fetal mice exposed during organogenesis, an
      effect considered to be due to heat-induced apoptosis of cells in the developing
      organs. We exposed pregnant mice carrying Trp53(+/+), Trp53(+/-) and Trp53(-/-)
      fetuses to mild whole-body hyperthermia that raised their core temperature to
      40.5 degrees C for 60 min on either day 10 or 11 of gestation. On day 18 of
      gestation, the fetuses were removed from control and hyperthermia-treated mice
      and genotyped, and tail length was measured. Limb digits were examined for
      abnormalities. Tail length in unheated control fetuses was influenced by Trp53
      status. A complete lack of functional Trp53 (Trp53(-/-)) but not partial lack of
      function (Trp53(+/-)) resulted in shorter tails compared to Trp53(+/+) fetuses,
      indicating a role for Trp53 in the regulation of tail lengthening in mouse
      fetuses. In all three genotypes, hyperthermia on gestation day 10 resulted in
      tails shorter than unheated controls, and hyperthermia on day 11 resulted in
      tails longer than controls. There was no effect on limb digit abnormalities. The
      data suggest that Trp53-dependent or independent apoptosis may not be directly
      involved in heat-induced teratogenesis, but that the primary teratogenic effect
      of heat results from the disruption of another tail length-regulating process
      that is independent of Trp53. However, the nature of the teratogenic outcome of
      that disruption depends on the gestation time. The ability of Trp53 to
      additionally regulate the tail lengthening process was also sensitive to the
      effects of heat, but that sensitivity again depended on the time of the heat
      stress during gestation.

PMID- 12236812
TI  - Radiation-induced teratogenic effects in fetal mice with varying Trp53 function:
      influence of prior heat stress.
AB  - Teratogenesis induced by radiation in fetal mice has been closely linked to Trp53
      dependent apoptosis. This study examined teratogenesis in tails and limb digits
      of fetal mice with varying Trp53 status after a 4-Gy radiation exposure, with and
      without a prior 40.5 degrees C, 60-min heat stress. Irradiation earlier in
      gestation (day 11) produced greater effects than later (day 12) exposure, but in
      both cases the maximum teratogenic effect of radiation occurred in Trp53 normal
      fetuses, the minimum in Trp53 null fetuses, and intermediate effects in Trp53
      heterozygotes, indicating dominance of Trp53-dependent apoptosis. Heat stress 24
      h prior to irradiation on day 11 did not alter the teratogenic effects in Trp53
      normal or heterozygous fetuses, but it reduced effects in the Trp53 null fetuses.
      Conversely, heat stress immediately before irradiation on day 11 amplified
      teratogenesis in Trp53 null fetuses, still with only a small or no effect on
      fetuses with full or partial Trp53 function, respectively. These results indicate
      little effect of mild heat on Trp53-dependent apoptosis after irradiation, but
      they also suggest heat-induced amplification of Trp53-independent processes that
      led to apoptosis when heat was delivered near the time of radiation exposure, and
      heat-induced protection of that process when sufficient expression time was
      allowed. However, Trp53-dependent apoptosis, when functional, acted as the
      ultimate determinant of radiation-induced teratogenic effects during early
      organogenesis. On gestation day 12, radiation effects were diminished, but heat
      stress 24 h prior to radiation exposure had a large amplifying effect in Trp53
      normal or heterozygous fetuses. In the absence of functional Trp53, the
      sensitizing effect of the heat was diminished. The results may suggest that at
      later times in organ development, DNA repair is more active, allowing some cells
      to escape radiation-induced Trp53-dependent apoptosis. However, heat may be able
      to significantly inhibit this active repair and increase the teratogenic effect
      of radiation. A diminished effect in the absence of functional Trp53 is
      consistent with an influence of heat on inhibiting DNA repair, but with a
      diminished probability of apoptosis.

PMID- 12236813
TI  - Influence of prior exposure to low-dose adapting radiation on radiation-induced
      teratogenic effects in fetal mice with varying Trp53 function.
AB  - Teratogenesis in tails and limb digits of fetal mice with varying Trp53 status
      was examined after exposure of pregnant females to 4 Gy gamma radiation with and
      without a prior 30-cGy exposure. Prior low-dose exposure modified the teratogenic
      effects of radiation in a manner dependent upon Trp53 status and gestation time.
      A 4-Gy exposure on gestation day 11 resulted in tail shortening and digit
      abnormalities. A 30-cGy exposure 24 h prior to a 4-Gy radiation exposure on day
      11 reduced the extent of both digit abnormalities and the tail-shortening effects
      in Trp53(+/+) fetuses and also reduced tail shortening in Trp53(+/-) fetuses, but
      to a lesser extent. However, the pre-exposure enhanced the tail-shortening
      effects of 4 Gy in Trp53(-/-) fetuses. In contrast, a 30-cGy exposure given 24 h
      prior to a 4-Gy exposure on gestation day 12 had no effect on the reduced tail
      length resulting from the 4-Gy exposure of Trp53(+/+) or Trp53(+/-) fetuses, but
      it partly protected Trp53(-/-) fetuses against reduced tail length. A 4-Gy
      exposure alone on day 12 did not result in any increase in the frequency of digit
      abnormalities in Trp53(-/-) fetuses so any protective effect of the
      preirradiation could not be detected. However, the preirradiation did result in
      protection against in digit abnormalities in Trp53(+/-) fetuses. We conclude that
      radiation-induced teratogenesis reflects both Trp53-dependent and independent
      processes that lead to apoptosis, and these respond differently to prior adapting
      doses.

PMID- 12236814
TI  - Clearance of radiation-induced apoptotic lymphocytes: ex vivo studies and an in
      vitro co-culture model.
AB  - Lymphocytes are very sensitive to radiation. Our aim was to test the possibility
      of detecting apoptosis in lymphocytes as a potential short-term biomarker of
      ionizing radiation exposure. Our in vitro data confirmed the dose-time-effect
      relationships involved in radiation-induced apoptosis. The detection of in vivo
      induction of apoptosis in circulating lymphocytes after exposure of animals to
      radiation appears to depend critically on the technique used to measure
      apoptosis. Among the different techniques we investigated, mitochondrial
      modification was the most appropriate; they allowed establishment of dose-time
      effect relationships when animals were observed for 72 h. A model of in vitro
      phagocytosis of apoptotic lymphocytes by macrophages was developed to mimic
      clearance of apoptotic cells occurring in vivo. Together, our data show that
      mitochondrial labeling may make it possible to detect ex vivo radiation-induced
      apoptosis of lymphocytes before macrophage ingestion occurs. We propose the
      measurement of apoptosis in lymphocytes as a potential short-term biomarker of
      ionizing radiation exposure.

PMID- 12236815
TI  - Response of thyroid follicular cells to gamma irradiation compared to proton
      irradiation: II. The role of connexin 32.
AB  - The objective of this study was to determine whether connexin 32-type gap
      junctions contribute to the "contact effect" in follicular thyrocytes and whether
      the response is influenced by radiation quality. Our previous studies
      demonstrated that early-passage follicular cultures of Fischer rat thyroid cells
      express functional connexin 32 gap junctions, with later-passage cultures
      expressing a truncated nonfunctional form of the protein. This model allowed us
      to assess the role of connexin 32 in radiation responsiveness without relying
      solely on chemical manipulation of gap junctions. The survival curves generated
      after gamma irradiation revealed that early-passage follicular cultures had
      significantly lower values of alpha (0.04 Gy(-1)) than later-passage cultures
      (0.11 Gy(-1)) (P < 0.0001, n = 12). As an additional way to determine whether
      connexin 32 was contributing to the difference in survival, cultures were treated
      with heptanol, resulting in higher alpha values, with early-passage cultures
      (0.10 Gy(-1)) nearly equivalent to untreated late-passage cultures (0.11 Gy(-1))
      (P > 0.1, n = 9). This strongly suggests that the presence of functional connexin
      32-type gap junctions was contributing to radiation resistance in gamma
      irradiated thyroid follicles. Survival curves from proton-irradiated cultures had
      alpha values that were not significantly different whether cells expressed
      functional connexin 32 (0.10 Gy(-1)), did not express connexin 32 (0.09 Gy(-1)),
      or were down-regulated (early-passage plus heptanol, 0.09 Gy(-1); late-passage
      plus heptanol, 0.12 Gy(-1)) (P > 0.1, n = 19). Thus, for proton irradiation, the
      presence of connexin 32-type gap junctional channels did not influence their
      radiosensitivity. Collectively, the data support the following conclusions. (1)
      The lower alpha values from the gamma-ray survival curves of the early-passage
      cultures suggest greater repair efficiency and/or enhanced resistance to
      radiation-induced damage, coincident with the expression of connexin 32-type gap
      junctions. (2) The increased sensitivity of FRTL-5 cells to proton irradiation
      was independent of their ability to communicate through connexin 32 gap
      junctions. (3) The fact that the beta components of the survival curves from both
      gamma rays and proton beams were similar (average 0.022 +/- 0.008 Gy(-2), P >
      0.1, n = 39) suggests that at higher doses the loss of viability occurs at a
      relatively constant rate and is independent of radiation quality and the presence
      of functional gap junctions.

PMID- 12236816
TI  - Quantitative detection of (125)IdU-induced DNA double-strand breaks with gamma
      H2AX antibody.
AB  - When mammalian cells are exposed to ionizing radiation and other agents that
      introduce DSBs into DNA, histone H2AX molecules in megabase chromatin regions
      adjacent to the breaks become phosphorylated within minutes on a specific serine
      residue. An antibody to this phosphoserine motif of human H2AX (gamma-H2AX)
      demonstrates that gamma-H2AX molecules appear in discrete nuclear foci. To
      establish the quantitative relationship between the number of these foci and the
      number of DSBs, we took advantage of the ability of (125)I, when incorporated
      into DNA, to generate one DNA DSB per radioactive disintegration. SF-268 and HT
      1080 cell cultures were grown in the presence of (125)IdU and processed
      immunocytochemically to determine the number of gamma-H2AX foci. The numbers of
      (125)IdU disintegrations per cell were measured by exposing the same
      immunocytochemically processed samples to a radiation-sensitive screen with known
      standards. Under appropriate conditions, the data yielded a direct correlation
      between the number of (125)I decays and the number of foci per cell, consistent
      with the assumptions that each (125)I decay yields a DNA DSB and each DNA DSB
      yields a visible gamma-H2AX focus. Based on these findings, we conclude that
      gamma-H2AX antibody may form the basis of a sensitive quantitative method for the
      detection of DNA DSBs in eukaryotic cells.

PMID- 12236817
TI  - On (3)H beta-particle and (60)Co gamma irradiation of aqueous systems.
AB  - The chemistry of water and aqueous solutions is very different after irradiation
      with (3)H beta particles and high-energy electrons or (60)Co gamma rays. The
      greater the linear energy transfer (LET) of the medium for (3)H beta particles
      compared to high-energy electrons or (60)Co gamma rays leads to an increased
      local concentration of reactants. There is an increased amount of intratrack
      chemistry, which reduces the escape yield of and OH by about 50%, but increases
      the yield of H(2) by about 50% and of H(2)O(2) by about 35%. Analysis of
      stochastic-diffusion kinetic calculations employing simulated track structures
      reveals that the yield of H(2) produced by diffusion-kinetic processes increases
      significantly for (3)H beta particles compared to (60)Co gamma radiation, while
      production of H(2) by sub-picosecond processes is essentially the same. In both
      (3)H beta-particle and (60)Co gamma radiolysis, the reactions + and are equally
      important in the production of H(2). In the former case, each reaction has a
      yield of approximately 0.18, and in the latter a yield of approximately 0.08. In
      neutral water, the reaction (H + H) is negligible. The yield of Fe(III) in (3)H
      beta-particle radiolysis of the Fricke dosimeter is much smaller than in
      radiolysis with more energetic electrons. Simulations show that this change is
      primarily due to the reduced escape yield of H, formed from the scavenging of by
      the bulk H(3)O(+) of the acid. The chemical differences observed in experiments,
      and in calculations, reflect the underlying structure of the electron tracks:
      Examination of the track structure simulations demonstrates that primary events
      are considerably more well-separated in high-energy electron tracks compared to
      (3)H beta-particle tracks.

PMID- 12236818
TI  - Enhanced values of the RBE and H ratio for cytogenetic effects induced by
      secondary electrons from an X-irradiated gold gurface.
AB  - The low-energy secondary electrons emerging from the entrance surface of an X
      irradiated gold foil increase the dose to cells in contact with or at micrometer
      distances from this surface (Radiat. Res. 150, 92-100, 1998). We examined the
      effect of the spectrum of these low-energy electrons on the RBE for cytogenetic
      effects and showed that this RBE was increased. A monolayer of surface-attached
      human T lymphocytes was exposed to 60 kV X rays in the absence or presence of a
      gold foil positioned immediately behind the cell layer or separated from it by a
      Mylar foil 0.9 or 2 microm thick. The enhancement of dose in the cell nuclei
      caused by the photoelectrons and Auger electrons emerging from the entrance
      surface of the gold foil was measured by TSEE dosimetry. Dose enhancement factors
      of 55.7, 46.6 and 37.5 were obtained with 0, 0.9 and 2 microm of Mylar inserted
      between the gold surface and the cell layer. This large enhancement results from
      the photoelectric effect in the gold foil, as shown by the accompanying Monte
      Carlo calculations of the secondary electron spectra at the gold surface. Auger
      electrons from the gold foil generally were not able to penetrate into the cell
      nuclei except for that fraction of the cells that had a very thin (< 0.7 microm)
      layer of cytoplasm and membranes between gold surface and cell nucleus. The dose
      yield curves for dicentric chromosomes plus centric rings and for acentric
      fragments obtained after exposures without or with the gold foil were linear
      quadratic. The coefficient alpha, the slope of the linear yield component, was
      increased in the presence of the gold foil and showed RBE values ranging from 1.7
      to 2.2 compared to exposures in absence of the gold foil. The ratio of the yield
      of interstitial deletions and dicentrics (H ratio) was significantly increased
      from about 0.17 in the absence of the gold foil to about 0.22 in the presence of
      the gold foil. The increases in the RBE and the H ratio are interpreted in
      microdosimetric terms: The preferred occurrence of electron track ends in the
      vicinity of the gold surface causes an increase in the dose-mean restricted
      linear energy transfer in cell nuclei exposed to the photoelectrons and Auger
      electrons.

PMID- 12236819
TI  - Scattering phenomena effects on growth of 308-nm laser-irradiated bacteria in
      suspension.
AB  - In this study we analyzed the effect of 308-nm laser exposure on recovery of
      irradiated Staphylococcus epidermidis held in liquid after irradiation and before
      plating. Coexistence of bacterial growth inhibition and stimulation phenomena was
      observed. Under certain conditions, bacterial recovery was about fivefold higher
      in irradiated samples than in the controls. The available evidence suggests that
      the growth inhibition was due to the bactericidal activity of the 308-nm
      wavelength light, whereas the growth stimulation effect was associated with
      broadband radiation generated by scattering phenomena in the bacterial
      suspensions. Spectroscopic investigations revealed that the nutrient broth plays
      a decisive role in the scattering of laser radiation within the suspension.

PMID- 12236820
TI  - DNA damage and micronucleus induction in human leukocytes after acute in vitro
      exposure to a 1.9 GHz continuous-wave radiofrequency field.
AB  - Human blood cultures were exposed to a 1.9 GHz continuous-wave (CW)
      radiofrequency (RF) field for 2 h using a series of six circularly polarized,
      cylindrical waveguides. Mean specific absorption rates (SARs) of 0.0, 0.1, 0.26,
      0.92, 2.4 and 10 W/kg were achieved, and the temperature within the cultures
      during a 2-h exposure was maintained at 37.0 +/- 0.5 degrees C. Concurrent
      negative (incubator) and positive (1.5 Gy (137)Cs gamma radiation) control
      cultures were run for each experiment. DNA damage was quantified immediately
      after RF-field exposure using the alkaline comet assay, and four parameters (tail
      ratio, tail moment, comet length and tail length) were used to assess DNA damage
      for each comet. No evidence of increased primary DNA damage was detected by any
      parameter for RF-field-exposed cultures at any SAR tested. The formation of
      micronuclei in the RF-field-exposed blood cell cultures was assessed using the
      cytokinesis-block micronucleus assay. There was no significant difference in the
      binucleated cell frequency, incidence of micronucleated binucleated cells, or
      total incidence of micronuclei between any of the RF-field-exposed cultures and
      the sham-exposed controls at any SAR tested. These results do not support the
      hypothesis that acute, nonthermalizing 1.9 GHz CW RF-field exposure causes DNA
      damage in cultured human leukocytes.

PMID- 12236821
TI  - DNA damage in human leukocytes after acute in vitro exposure to a 1.9 GHz pulse
      modulated radiofrequency field.
AB  - Blood cultures from human volunteers were exposed to an acute 1.9 GHz pulse
      modulated radiofrequency (RF) field for 2 h using a series of six circularly
      polarized, cylindrical waveguides. Mean specific absorption rates (SARs) ranged
      from 0 to 10 W/kg, and the temperature within the cultures during the exposure
      was maintained at 37.0 +/- 0.5 degrees C. DNA damage was quantified in leukocytes
      by the alkaline comet assay and the cytokinesis-block micronucleus assay. When
      compared to the sham-treated controls, no evidence of increased primary DNA
      damage was detected by any parameter for any of the RF-field-exposed cultures
      when evaluated using the alkaline comet assay. Furthermore, no significant
      differences in the frequency of binucleated cells, incidence of micronucleated
      binucleated cells, or total incidence of micronuclei were detected between any of
      the RF-field-exposed cultures and the sham-treated control at any SAR tested.
      These results do not support the hypothesis that acute, nonthermalizing 1.9 GHz
      pulse-modulated RF-field exposure causes DNA damage in cultured human leukocytes.

PMID- 12236822
TI  - Detection and characterization of formamido lesions in DNA by liquid
      chromatography-mass spectrometry.
AB  - DNA X-irradiated in oxygenated aqueous solution produces the formamido lesion
      from the breakdown of pyrimidine nucleosides. This pyrimidine breakdown product
      inhibits the hydrolysis by nuclease P1 of the phosphoester bond 3' to the damaged
      nucleoside. Consequently, the lesion can be obtained from an enzymatic digest of
      the DNA as a modified dinucleoside monophosphate in which the 5' nucleoside
      contains the lesion. In this form, the formamido lesion can be detected with good
      sensitivity by liquid chromatography-mass spectrometry (LC-MS). Nucleosides that
      have lost the base moiety also inhibit nuclease P1. Together, the formamido and
      abasic lesions account for all of the substantial peaks in the LC-MS ion current
      profile.

PMID- 12236823
TI  - Private dental visits per dentist in Spain from 1987 to 1997. An analysis from
      the Spanish national Health Interview Surveys.
AB  - OBJECTIVES: In view of the sharp increase in the number of dentists in Spain, the
      aim of the present study was to analyse changes in the private dentist workload
      in Spain over the period 1987-97. METHODS: Data were taken from censuses of the
      population and of dental practitioners, and from the Spanish National Health
      Interview Surveys. The percentage of people that had visited the dentist in the 3
      months prior to the survey was calculated, and of these, the percentage whose
      last visit was private. The total number of visits made by those people was taken
      as the estimate of total private visits in Spain during 3 months. Total private
      activity in 1 year was derived by multiplying this estimate by four. Annual
      private activity was then divided by the number of dentists. RESULTS: From 1987
      to 1997, the Spanish population grew 2.5% (from 38.7 to 39.7 million) and the
      number of dentists increased by 136.1% (from 6373 to 15,044). The total annual
      number of private dental visits (+/-SE) was 35.7 +/- 1.0 million in 1987, and
      48.9 +/- 2.0 million in 1997 - a 36.8% increase. Thus, the mean number of private
      dental visits per dentist decreased 42.0% (from 5610 +/- 152 to 3251 +/- 133).
      CONCLUSION: A significant reduction in private dental visits per dentist is
      taking place in Spain.

PMID- 12236824
TI  - Predicting the experience of dentinal caries or restorative dental treatment in
      adolescents using D1 and D3 visual caries assessments.
AB  - Standardised epidemiological caries assessments used in oral health surveys have
      been shown to be poor at predicting whether a tooth surface will be treated
      restoratively when a patient visits a dentist. However, it has been argued that
      oral health surveys may be more relevant in determining needs at the level of an
      individual or groups of individuals. The objective of this study was to determine
      the discriminatory power of visual caries assessments at two thresholds (D1 & D3)
      in adolescents of average age 12.1 years to predict experience of dentinal caries
      3 years later or the experience of restorative treatment (not re-treatment)
      during the 3-year period. The data was derived from a prospective 3-year
      longitudinal study in which the dental care provided by 41 dentists for 403
      adolescents was monitored. Dental caries experience was monitored by annual
      standardised assessments of caries undertaken by a single trained examiner. ROC
      analysis showed that caries assessed visually at the D1 threshold in 12-year-olds
      was a better predictor (P < 0.001) of experiencing some dentinal caries after 3
      years (Az = 0.781) than was caries assessed visually at D3 threshold in 12-year
      olds (Az = 0.670). Assessing caries visually at either the D1 or the D3 threshold
      had no discriminatory power for predicting whether an individual would experience
      some restorative treatment during the ensuing 3-year period (Az for D1 = 0.507;
      Az for D3 = 0.518).

PMID- 12236825
TI  - Cost-effectiveness of screening for the possible development of cancer in
      patients with oral lichen planus.
AB  - INTRODUCTION: Several authors have expressed the view that patients with oral
      lichen planus (OLP) are at increased risk of developing oral cancer. Since OLP
      cannot be effectively treated, regular screening for the possible development of
      oral cancer might be considered. OBJECTIVES: (i) To calculate costs and
      effectiveness of screening for oral cancer in OLP patients with a decision model;
      (ii) to compare the cost-effectiveness of different screening scenarios; and
      (iii) to perform a sensitivity analysis of several variables used in this model.
      METHODS: Costs and effectiveness of a population of 100,000 OLP patients, being
      either screened or not screened for oral cancer, were calculated for the period
      of 1 year. Health gain was expressed as quality adjusted live years (QALY's) and
      equivalent lives saved (ELS). Cost-effectiveness was expressed as extra costs
      (costs of screening minus costs of no screening) per ELS. Then, the outcome was
      compared with the cost-effectiveness of a different screening scenario. Finally,
      the effect of varying the variables: (i) costs of cancer treatment; (ii) annual
      malignant transformation rate (MTR); (iii) sensitivity and specificity of an oral
      examination; and (iv) proportion of cancers found in stage I on extra costs per
      ELS were assessed in a sensitivity analysis. RESULTS: The health gain from
      screening was 592 QALY's or the equivalent of 23.68 lives saved, costing
      1,265,229 dollars, meaning that one ELS costed 53,430 dollars. Increase of cancer
      treatment costs will significantly decrease the costs per ELS. When the MTR is
      lower than 0.4% per year, extra costs per ELS will increase exponentially. The
      effect of sensitivity and specificity of an oral examination in detecting oral
      cancer on cost-effectiveness seems to be substantial. When the proportion of
      cancers found in stage I can be increased from 40% (without screening) up to at
      least 60% after screening, extra costs per ELS will decrease exponentially.
      CONCLUSIONS: Screening for oral cancer in OLP patients, based on the presently
      used model, seems attractive. However, varying the several variables in the
      decision model has a significant impact on the final costs and effectiveness.
      Only, when additional information about these variables will become available, a
      more precise and realistic calculation can be performed.

PMID- 12236826
TI  - A prospective study of the validity of data on self-reported dental visits.
AB  - OBJECTIVE: To measure the validity of self-reported dental visits from a diverse
      sample of adults. METHODS: The Florida Dental Care Study was a longitudinal
      cohort study of a diverse sample of residents of north Florida, USA. In-person
      interviews and dental examinations were conducted at baseline, 24 and 48 months
      after baseline, with half-yearly telephone interviews in between. Dental record
      information was abstracted afterward. RESULTS: Agreement between self-report and
      dental record at each half-yearly interview ranged from 84 to 91%. Validity did
      not differ between persons of key sociodemographic groups (sex, race, age group,
      rural/urban residence, poverty status, level of formal education, or problem
      oriented/regular approach to dental care). In a single bivariate multiple
      logistic regression (two outcomes: (i) self-reported use; and (ii) use measured
      from the dental chart), odds ratio estimates over-lapped for each of the 20
      predictors. CONCLUSIONS: Validity of self-reported dental care use was good.
      There would have been few differences in conclusions made about predictors of
      dental care use had chart data been available earlier.

PMID- 12236827
TI  - Effectiveness of chlorhexidine-thymol varnish for caries reduction in permanent
      first molars of 6-7-year-old children: 24-month clinical trial.
AB  - OBJECTIVES: To determine the effect of chlorhexidine varnish on the prevention of
      caries in permanent first molars. METHODS: Two groups of 6-7-year-old school
      children were followed up in a clinical trial, a group of 86 children whose teeth
      were treated with a chlorhexidine-thymol varnish (Cervitec) and a control group
      of 95 children. The varnish was reapplied every 3 months and the caries
      increments were compared at 24 months. RESULTS: The DFS (decayed and filled
      surfaces in permanent first molars) increment in the control group (mean = 1.85;
      SD = 2.27) was higher than in the test group (mean = 0.95; SD = 1.38), resulting
      in a 48.6% caries reduction. This difference was statistically significant (P =
      0.032). CONCLUSIONS: Chlorhexidine-thymol varnish is effective in preventing
      caries in permanent first molars.

PMID- 12236828
TI  - Disparities in dental service utilization among Alabama Medicaid children.
AB  - OBJECTIVES: Access to oral health care and utilization of available services are
      important factors in minimizing the oral health disparities among underserved
      minorities. Our objective was to evaluate the racial and other factors related to
      'realized access' to oral health care among Alabama Medicaid children. METHODS:
      Data were obtained from 308 538 Alabama Medicaid claims submitted in 1995-96 and
      analyzed using regression analyses. RESULTS: A lower proportion of Blacks (24%)
      and other racial groups (22%) compared to Whites (31%) and a lower proportion of
      15-19-year-olds (15%) compared to younger age groups (30%) obtained dental
      services (P < 0.05). Odds of males obtaining care were slightly lower compared to
      females (OR = 0.96; 95% CI = 0.94-0.99). However, there was a significant
      interaction of race with other factors in determining service utilization.
      Subjects who were continuously eligible for Medicaid throughout the fiscal year
      were more likely to obtain care (OR = 2.86; 95% CI = 2.78-2.93). About one-fourth
      of the visits had an emergency procedure included in the treatment rendered.
      Availability of a participating dentist within the county of residence and the
      lower reimbursement-to-charge ratio were among the other related factors for
      underutilization of services. CONCLUSIONS: There is a significant racial
      disparity in utilization of dental services even among the Medicaid-eligible
      children. However, this was not a simple function of race, but a complex
      interaction of race with other factors such as age, gender, and location.
      ACKNOWLEDGMENT: Supported by CDC grant #U48/CCU 409679.

PMID- 12236829
TI  - Response to direct and indirect recruitment for a randomised dental clinical
      trial in a multicultural population of elders.
AB  - OBJECTIVES: Recruitment for randomised clinical trials and community-based
      studies has received little attention in the dental literature. The goal of this
      study was to report on our experiences with direct and indirect recruitment
      methods for a trial to prevent tooth loss in elders. METHODS: A direct approach,
      consisting of an introductory lecture with the help of a local contact person in
      each of the nine community centres, resulted in 208 recruits mostly from minority
      non-English speaking communities (52%), whereas the other 192 recruits who
      responded to newspaper announcements (48%) were, in large part, from the English
      speaking community. RESULTS: The response suggests that a more direct and
      culturally specific approach is more productive when recruiting elders from
      ethnic minority groups, whereas elders from the dominant culture can be recruited
      indirectly and for about half the financial cost through newspaper announcements.
      CONCLUSION: We conclude, therefore, that both direct and indirect methods are
      needed to recruit a multiethnic sample of subjects for a trial.

PMID- 12236830
TI  - The fluoride content of foods and beverages from negligibly and optimally
      fluoridated communities.
AB  - In the spring of 1996, foods and beverages most commonly consumed by adolescents
      were analyzed for fluoride as part of a larger investigation. These foods were
      selected by interviewing 711 adolescents, 12-14 years of age, who were long-time
      residents of either an optimally or negligibly fluoridated community. The brand
      names of the identified foods and beverages most commonly purchased were
      determined by interviews with the parents. A total of 441 brand-name food and
      beverage items were purchased from both communities and were individually
      analyzed for fluoride. These analyses were done in order to estimate the fluoride
      content of various kinds of foods and beverages and to determine whether or not
      there was a significant difference between the two communities in the amount of
      fluoride ingested from these dietary sources. The food and beverage items were
      classified into dietary groups based on US Department of Agriculture (USDA)
      guidelines. Overall, the fluoride content of the sampled foods and beverages was
      low. In addition, there was no significant difference in the fluoride content of
      the same pre-packaged or ready-to-eat food or beverage items purchased in the two
      communities. However, a significant difference was found between the two
      communities in the fluoride content of fountain beverages and in cooked or
      reconstituted foods prepared using local water from the respective communities.
      Based on these results, we have estimated the mean daily, dietary fluoride intake
      for 3-5-year-old children who are more susceptible to developing dental
      fluorosis.

PMID- 12236831
TI  - The relationship between problem behaviour and traumatic dental injury amongst
      children aged 7-15 years old.
AB  - AIM: The aim of this study was to test whether dental injuries are related to
      problem behaviour. In addition, it aimed to confirm the relationship between
      dental injuries and size of overjet and type of lip coverage. METHODS: A hospital
      based matched (age and sex) case-control design was adopted. Data were collected
      through clinical examinations and interviews. The informant-rated version of the
      Strengths and Difficulties Questionnaire (SDQ) was used to identify problem
      behaviour. One parent of the child, most often the mother, was interviewed.
      Hierarchical modelling using conditional logistic regression was used to test the
      relationship between the five problem behaviours and traumatic dental injuries.
      RESULTS: The Odds ratio of having a dental injury increased 3.14 times if
      children have peer relationship problems (P = 0.032), whilst a prosocial
      behaviour showed a tendency to have a protective effect (OR = 0.25; P = 0.064).
      Emotional symptoms, conduct disorder and hyperactivity behaviours were not
      related to dental injury (P > 0.75). Results were adjusted by father's level of
      education, size of overjet and type of lip coverage, and these variables were
      significantly related to dental injury (P < 0.05). CONCLUSION: Problem behaviour
      may play an important role in the occurrence of traumatic dental injury.

PMID- 12236833
TI  - The resiliency of the human spirit.

PMID- 12236834
TI  - Diagnosing breast cancer with synchronous metastatic melanoma.

PMID- 12236835
TI  - Evaluating post-treatment screening in women with breast cancer.
AB  - PURPOSE: The objective of this study was to evaluate the 5-year post-treatment
      use rate for screening mammography and clinical breast examination (CBE) among
      women treated for atypical hyperplasia (AH) or carcinoma in situ (CIS).
      DESCRIPTION OF STUDY: A total of 103 women, who had received diagnoses and had
      been treated for primary AH or CIS, were observed for 5 years through a review of
      medical records and electronic databases. Adequate screening use was defined as
      the patient undergoing one mammography examination and at least one CBE per year.
      RESULTS: Multivariate logistic regression showed that screening activity declined
      significantly with time. During the first year, 83.5% and 80.6%, respectively, of
      women were screened by CBE and mammography. By year 2, CBE screening had dropped
      by 25.2% (P <.01) and mammography screening by 9.7% (P =.08). Attrition in CBE
      and mammography screening continued for each consecutive year and was significant
      (P <.01). During the first year, 70.9% of women received both methods of
      screening, which declined to 9.7% by year 5. Women who had received diagnoses of
      CIS and those married with children were more likely to use post-treatment
      screening, while fee-for-service insurance was negatively associated with
      screening. CLINICAL IMPLICATIONS: The reasons for the observed decline in the
      annual post-treatment screening are not known. Negative findings from follow-up
      screenings might have lowered the perception of cancer susceptibility and
      promoted the decline in screening use. A communication gap between physicians and
      patients might have reinforced this perception. The importance of annual
      screening may be verbally emphasized at each clinic visit, and reminder notes and
      telephone calls may be used to remind patients of upcoming screenings. Additional
      studies are planned to evaluate the effect of various intervention strategies in
      improving post-treatment screening use.

PMID- 12236836
TI  - An evaluation of the Man to Man self-help group in Colorado and Utah.
AB  - PURPOSE: Two surveys were conducted to evaluate the Man to Man program, a
      prostate cancer self-help group of the American Cancer Society (ACS). DESCRIPTION
      OF STUDY: The study involved two surveys in Colorado and Utah in 2001, one of
      program participants, the other of area urologists, respectively. A focus group
      also was conducted of African American men with prostate cancer in Denver, Colo.
      RESULTS: In total, 112 participants in the Man to Man program and 66 urologists
      participated in the study. Results of the participant survey indicated that men
      and their families found out about the group through other prostate cancer
      survivors, doctors, or the ACS. Monthly attendance at the groups ranged from 2 to
      50 participants. Participants valued the prostate cancer treatment information,
      physician presentations, and social aspects that were offered. The results of the
      urologist survey indicated that 67% were aware of the Man to Man program, but
      most were not aware of the services it offered. Urologists learned of the group
      through Man to Man participants, other physicians, and the ACS. Focus group
      results suggested that a personal preference for access to other sources of
      support and information was a primary reason for nonattendance at Man to Man
      meetings. CLINICAL IMPLICATIONS: Attendance at Man to Man meetings is likely to
      be enhanced by focusing on basic prostate cancer information topics. Future
      evaluations of Man to Man meeting participation should focus on the role of women
      in the program. Most urologists were not familiar with the services offered by
      Man to Man. The ACS and the organizers of local Man to Man programs should target
      urologists in future outreach efforts.

PMID- 12236837
TI  - Colorectal cancer screening barriers in persons with low income.
AB  - PURPOSE: The purpose of this study was to provide insight into the modest success
      of a physician and patient education and reminder program that improved screening
      rates from 37% to 49% among rural Medicaid-eligible patients in western Michigan.
      DESCRIPTION OF STUDY: The following four focus groups were conducted: African
      American men, African American women, White men, and White women, matched with
      moderators by gender and ethnicity. The sample was selected by contacting prior
      eligible screening refusers, completing groups with a convenience sample who had
      accepted screening. Twenty-one patients participated who were ages >50 years. The
      screening refusal rates were 19% for men and 9% for women. Open-ended questions
      guided the discussion of colorectal cancer (CRC) attitudes, beliefs, and
      practices. RESULTS: All participants believed in the efficacy of cancer
      screening. White women were better informed about screening purposes and
      procedures. The major barriers to screening were quality of care (ie, the
      perceived lack of offering screening and the follow-up of test results) and the
      potential for pain from screening or treatment of CRC, should it be discovered.
      CLINICAL IMPLICATIONS: Successful efforts to improve awareness of the importance
      and efficacy of screening must further address deeply held skepticism and fears
      about CRC screening in this population. A fruitful direction for this difficult
      problem appears to be improved communication (both negative and positive test
      results). Without feedback, patients with negative results may assume lack of
      provider follow-through.

PMID- 12236838
TI  - Indirect economic effects of long-term breast cancer survival.
AB  - PURPOSE: The indirect morbidity/disability costs of breast cancer may be rising
      as a consequence of the growth in the population of long-term survivors. This
      study was conducted to test whether women who have survived breast cancer for at
      least 5 years experience long-lasting or continuing economic consequences that
      are attributable to their disease. DESCRIPTION OF STUDY: A group of 105 women who
      initially had been treated for breast cancer approximately 5 years before were
      interviewed to obtain data on economic, demographic, and health changes in the
      period since diagnosis. An age-matched and work-matched group of 105 women
      without cancer also was interviewed to obtain the same data for the same time
      period. Key changes in the economic position of subjects and their families were
      measured, including changes in work effort, pay rates, and annual earnings of
      working women and changes in household earnings, income, and assets of all women.
      RESULTS: These preliminary empirical findings suggest that breast cancer exacts
      an economic toll from long-term survivors. In particular, survivors who were
      working at the time of their diagnosis experienced significantly larger
      reductions in annual market earnings over the 5-year study period than did
      working control subjects. These losses appear to arise mostly from reduced work
      effort, not changes in pay rates. Also, changes in total household earnings were
      lower for survivors, suggesting the presence of family adjustments to the
      disease. However, no significant differences were detected between the groups in
      changes in total income or assets over the study period. CLINICAL IMPLICATIONS:
      Clinicians and policy makers must seek ways to minimize the indirect economic
      losses that are attributable to breast cancer.

PMID- 12236839
TI  - Perceived risk of breast cancer: influence of heuristic thinking.
AB  - PURPOSE: The purpose of this study was to examine the influence of heuristic
      reasoning on women's perceived risk for developing breast cancer, and to test for
      an expected bias in the direction of optimism that is predicted by recent
      research on human cognition. DESCRIPTION OF STUDY: In total, 770 women recruited
      in community settings were surveyed regarding cancer screening behavior and their
      perceived risk of developing breast cancer. RESULTS: Most women perceived their
      risk of breast cancer to be lower than that of other women (3:1), confirming the
      expected bias toward optimism, and this finding was not attributable to the
      personality trait of optimism. Women following mammography guidelines showed
      greater optimism that their risk was low. Cancer knowledge and education
      diminished unwarranted optimism. Women with a history of benign breast disease,
      with a female relative with breast cancer, or both overestimated their risk. All
      findings suggest that heuristic thinking is being used to estimate personal
      cancer risk. CLINICAL IMPLICATIONS: Clinicians should expect women to be
      optimistic about their personal risk of developing breast cancer. As a result,
      women may put off breast cancer screening or delay the evaluation of breast
      symptoms that may signal breast cancer. Helping women to understand their
      relative risk is an essential part of a health promotion visit.

PMID- 12236841
TI  - Developing cancer clinical trial resources for Native Americans.

PMID- 12236843
TI  - Stereoselective urinary excretion of formoterol and its glucuronide conjugate in
      human.
AB  - AIMS: Formoterol is an inhaled beta2-adrenoceptor agonist used as a racemic
      mixture of the active (R; R)- and inactive (S; S)-enantiomers (rac-formoterol).
      Glucuronidation is an important route of metabolism in humans which occurs faster
      for (S; S)-formoterol in human liver microsomes. The aim of this study was to
      investigate the stereoselectivity of urinary excretion of formoterol and its
      glucuronide conjugate after oral dosing with rac-formoterol. METHODS: Seven
      nonsmoking volunteers (six males, one female) were included in the study. After
      an overnight fast, a single 60 micro g oral dose of rac-formoterol fumarate
      dihydrate was ingested. Urine samples were collected at 1 h intervals for the
      first 4 h, and at 6, 8, 12 and 24 h after dosing. Formoterol enantiomers were
      analysed by chiral h.p.l.c. assay and formoterol glucuronides were determined as
      formoterol enantiomers after enzymatic cleavage with beta-glucuronidase. RESULTS:
      The female subject displayed a different pattern of metabolism and statistical
      analysis was therefore limited to data for the six males. The median (range) of
      the total urinary excretion of formoterol was 37.8% (20.9-51.2%) of the dose. The
      medians (ranges) of the amounts of (R; R)- and (S; S)-formoterol and of (R; R)-
      and (S; S)-formoterol glucuronide excreted were 2.1 (1.0-2.9), 3.5 (2.6-3.8),
      21.0 (13.1-31.0) and 10.3 (4.2-14.6)%, respectively, of the dose. Unchanged (S;
      S)-formoterol excretion was significantly greater than that of unchanged (R; R)
      formoterol and (R; R)-formoterol glucuronide excretion was significantly greater
      than that of (S; S)-formoterol glucuronide. The total RR-formoterol (unchanged
      drug plus glucuronide) excreted was significantly greater than the total (S; S)
      formoterol. CONCLUSIONS: Our study demonstrates that the urinary excretion of
      formoterol in male humans after oral administration of rac-formoterol is
      stereoselective with preferential excretion of the active (R; R)-formoterol as
      unchanged drug and glucuronide. The different pattern of metabolism in the female
      subject provides impetus for further studies of the effect of gender on the
      stereoselective metabolism and pharmacokinetics of formoterol.

PMID- 12236842
TI  - Antagonism of long-acting beta2-adrenoceptor agonism.
AB  - The established place of regular long-acting beta2-adrenoceptor agonists at step
      3 in asthma management guidelines has evolved as a consequence of evidence
      showing additive effects of salmeterol and formoterol on exacerbation rates,
      resulting in a putative inhaled corticosteroid sparing effect. There is however,
      evidence to show that although long-acting beta2-adrenoceptor agonists facilitate
      using a lower dose of inhaled corticosteroid, this may occur at the expense of
      suboptimal anti-inflammatory control. This is likely to be the case especially
      with fixed dose combination inhalers where it is not possible to properly titrate
      anti-inflammatory therapy with inhaled corticosteroids without also inadvertently
      overtreating with unnecessarily high doses of long-acting beta2-adrenoceptor
      agonists. Most patients with mild to moderate persistent asthma can be adequately
      controlled on monotherapy with inhaled corticosteroid in low or medium dosage,
      which is considerably cheaper than concomitant use of a long-acting beta2
      adrenoceptor agonist. Subsensitivity to long-acting beta2-adrenoceptor agonists
      is a predictable pharmacological phenomenon which occurs despite concomitant
      inhaled corticosteroid therapy and occurs more readily for bronchoprotective than
      bronchodilator effects. Subsensitivity of salbutamol protection against
      bronchoconstrictor stimuli occurs in patients receiving concomitant long-acting
      beta2-adrenoceptor agonists, which may be due to beta2-adrenoceptor down
      regulation or prolonged receptor occupancy. Prospective large scale long-term
      studies are required to further define the clinical relevance of beta2
      adrenoceptor polymorphisms, to look at clinical control outcomes as well as
      propensity for subsensitivity. It would therefore make more sense to first of all
      optimize the dose of anti-inflammatory therapy with inhaled corticosteroid and to
      then consider adding a long-acting beta2-adrenoceptor agonist for patients who
      are poorly controlled.

PMID- 12236844
TI  - Quinidine does not affect the renal clearance of moxonidine.
AB  - AIMS: To test the hypothesis that the renal clearance of moxonidine decreases
      when dosed with quinidine. METHODS: A randomized, two-period study was conducted
      with six healthy, male subjects orally dosed with either 0.2 mg moxonidine alone
      or 1 h after 400 mg quinidine sulphate. Pharmacokinetic parameters were
      calculated using a noncompartmental analysis method. RESULTS: When
      coadministered, quinidine significantly increased moxonidine AUC and t1/2 by 11%
      and 15%, respectively, and decreased CL/F by 10% compared with the control
      dosing. CLR and Aeur were not significantly different. Clinically, both
      treatments were well tolerated. CONCLUSIONS: Quinidine does not affect the renal
      clearance of moxonidine. The decrease in apparent total clearance of moxonidine
      with quinidine coadministration was possibly due to metabolic inhibition, though
      not likely to be clinically significant.

PMID- 12236845
TI  - Pharmacokinetics and gamma scintigraphy evaluation of two enteric coated
      formulations of didanosine in healthy volunteers.
AB  - AIMS: The aims of the study were to evaluate the bioavailability of didanosine
      from the encapsulated enteric coated beads (1 x 200 mg; enteric beads) and
      enteric coated mini-tablets (4 x 50 mg; enteric tablet) formulations relative to
      the chewable/dispersible buffered tablets (2 x 100 mg; buffered tablet), and to
      study their rate of gastrointestinal transit. METHODS: This was a single-dose,
      randomized, three-way crossover study in 18 healthy male volunteers. A 200 mg
      dose of didanosine was given in each period and each formulation contained a
      gamma radiation-emitting isotope. Pharmacokinetic parameters determined were
      Cmax, tmax, AUC(0, infinity ) and t1/2. Bioequivalence was assessed using the
      confidence interval (CI) of 0.80, 1.25 for Cmax and AUC(0, infinity ).
      Scintigraphic images were recorded and gastrointestinal transit profiles were
      generated. RESULTS: The point estimate and 90% CI of the ratio of Cmax for the
      enteric beads and enteric tablet relative to the buffered tablet was 0.71 (0.59,
      0.85) and 0.55 (0.46, 0.66), respectively. The tmax was significantly different
      for the enteric beads (median, 1.33 h) and the enteric tablet (median, 2.83 h)
      than for the buffered tablet (median, 0.67 h). The AUC(0, infinity ) satisfied
      the bioequivalence criteria, and the point estimate and 90% CI of the ratio were
      1.02 (0.91, 1.15) and 0.92 (0.82, 1.04) for the enteric beads and enteric tablet,
      respectively. The AUC(0, infinity ) values appeared to be less variable with the
      enteric beads (% CV = 19%) than with the enteric tablet (% CV = 33%). The t1/2
      values were not significantly different between formulations, and the mean values
      ranged from 1.82 to 1.92 h. Inspection of the individual scintigraphy profiles
      and concentration-time curves suggested that didanosine was absorbed throughout
      the small intestine. Gastrointestinal transit parameters were higher for both
      enteric formulations than for the buffered tablet, indicating slower transit of
      the enteric formulations. Between the enteric formulations, gastric emptying was
      slower for the enteric beads than for the enteric tablet; however, plasma
      didanosine concentrations were observed sooner for the enteric beads, suggesting
      that the enteric coat for the beads dissolved more rapidly. CONCLUSIONS: The
      enteric beads and enteric tablet formulations of didanosine were equivalent to
      the buffered tablet in their extent of absorption. Although the gastric emptying
      of the enteric tablet was faster, based on the rapid uncoating and the lower
      variability in AUC, the enteric beads were chosen for further clinical
      development.

PMID- 12236846
TI  - The unbound percentage of saquinavir and indinavir remains constant throughout
      the dosing interval in HIV positive subjects.
AB  - AIMS: To measure the unbound plasma concentrations of saquinavir (SQV) and
      indinavir (IDV) and to relate them to the total plasma concentrations in order to
      establish the unbound percentage of protease inhibitors in vivo during a full
      dosage interval profile. METHODS: HIV-infected subjects (n = 35; median CD4 cell
      count = 340 x 10(6) cells l-1, range: 120-825; viral load < 50 copies ml-1 in
      22/35) treated with SQV or IDV containing regimens were studied. Plasma drug
      samples were collected at 0, 2, 4, 8 and 12 h postdose for the twice daily
      regimens and 0, 1, 2, 4 and 8 h for the three times daily regimens. Ultra
      filtration was used to separate unbound IDV and SQV in plasma and their
      respective concentrations were measured by a fully validated method using high
      performance liquid chromatography-mass spectometry (h.p.l.c.-MS/MS). RESULTS:
      Based on the ratio AUCunbound/AUCtotal, the median unbound percentage (95% CI for
      differences) of SQV and IDV from all the samples studied was 1.19% (0.99, 1.58%)
      and 36.3% (35.1, 44.2%), respectively. No significant difference was seen in the
      percentage binding of SQV between patients receiving SQV alone (median = 1.49%)
      or with ritonavir (median = 1.09%; P = 0.141; 95% CI for difference between
      medians = -0.145, 0.937) over the pharmacokinetic profile. Similarly, no
      significant difference was seen in the percentage binding of IDV in patients
      receiving IDV alone (median 35.2%) or with ritonavir (median = 41.3%; P = 0.069;
      95% CI for difference between medians = -0.09, 15.4). The unbound concentrations
      of SQV (P < 0.0001; 95% CI for r(2) = 0.634, 0.815) and IDV (P < 0.0001; 95% CI
      for r(2) = 0.830, 0.925) remained constant as a proportion of total concentration
      over the full dosing profile. CONCLUSIONS: These in vivo data confirm previously
      published in vitro measurements of SQV and IDV protein binding. The unbound
      percentage of both protease inhibitors remained constant over the dosing
      interval.

PMID- 12236847
TI  - Early clinical experience with the novel proteasome inhibitor PS-519.
AB  - AIMS: The main objective of this study was to investigate the safety,
      tolerability and pharmacodynamics of the novel proteasome inhibitor PS-519 in
      young male volunteers. Many pro-inflammatory mediators such as cytokines and cell
      adhesion molecules that are responsible for the development of the cerebral
      infarct are under the control of the transcription factor Nuclear Factor kappa-B
      (NF-kappaB). The activity of NF-kappaB is itself tightly regulated through the
      multicatalytic enzyme known as the proteasome. PS-519 is a novel and highly
      selective small molecule that inhibits the proteasome. An ex vivo assay of 20S
      proteasome activity allows monitoring of the drug effect in blood. PS-519 is
      protective in multiple animal models of cerebral ischaemia over a range of doses
      that achieve 20S inhibition of 40%-80%. METHODS: PS-519 has been administered to
      healthy male volunteers as single and repeated doses up to 1.6 mg m(-2). It was
      given as an intravenous bolus over 20-30 s in a double blind, randomized, placebo
      controlled phase I study, examining vital signs, safety, tolerability and blood
      20S proteasome inhibition. RESULTS: Thirty-nine subjects received single doses of
      0.012 mg m-2-1.6 mg m(-2) and 28 subjects received doses of 0.5 mg m(-2)-1.6 mg
      m(-2) on three consecutive days. The drug was well tolerated. There was no clear
      treatment-emergent symptom or abnormality of laboratory tests. Proteasome
      inhibition in blood samples as measured by 20S assay achieved the intended
      maximum target level of 70-80% with 1.6 mg m(-2), and was reproducible with
      repeated dosing. CONCLUSIONS: This study has demonstrated that proteasome
      inhibition is well tolerated by healthy subjects at levels that are maximally
      neuroprotective in experimental conditions. Further clinical evaluation appears
      justified.

PMID- 12236848
TI  - The effects of St John's wort extract on heart rate variability, cognitive
      function and quantitative EEG: a comparison with amitriptyline and placebo in
      healthy men.
AB  - AIMS: To compare the effects of multiple dosing with St John's wort (Hypericum
      perforatum) extract and amitriptyline on heart rate variability, cognitive
      function and quantitative EEG (qEEG) with placebo in healthy humans. METHODS: A
      randomized, double-blind, cross over study of 12 healthy male volunteers.
      Subjects orally received capsules with 255-285 mg St John's wort extract (900
      micro g hypericin content), 25 mg amitriptyline and placebo three times daily for
      periods of 14 days each with at least 14 days between. The doses of amitriptyline
      and St John's wort extract are comparable with respect to their antidepressant
      activity. Compliance was confirmed by coadministration of 10 mg of riboflavin
      with each capsule and detection of urinary vitamin B2 on treatment day 11 with
      high performance liquid chromatography. Measurements of heart rate variability,
      psychometric tests and qEEG were performed before start of medication and
      repeatedly on the last treatment day. RESULTS: St John's wort extract did not
      affect heart rate variability (HRV) whereas amitripytline significantly decreased
      it: the difference in the percentage number of adjacent RR intervals> 50 ms
      (pNN50) was 8.6 (-2.6, 19.9; mean; 95% confidence interval) between St John's
      wort extract and placebo and -17.6 (-24.7, -10.4) between amitriptyline and
      placebo. Neither St John's wort extract nor amitriptyline had an influence on
      cognitive performance such as choice reaction, psychomotor coordination, short
      term memory and responsiveness to distractive stimuli. Amitriptyline but not St
      John's wort extract decreased self rated activity (P < 0.05). Both drugs caused
      significant qEEG changes. St John's wort extract increased theta power density.
      Amitriptyline increased theta as well as fast alpha power density. CONCLUSIONS:
      Multiple doses of St John's wort extract do not affect heart rate variability nor
      cognitive function. Chronic administration of amitriptyline causes a decrement of
      HRV and subjective sedation but it does not impair cognitive performance.

PMID- 12236849
TI  - Pharmacokinetics and pharmacodynamics of TF-505, a novel nonsteroidal 5alpha
      reductase inhibitor, in normal subjects treated with single or multiple doses.
AB  - AIMS: To assess the tolerability, pharmacokinetics and pharmacodynamics of a
      novel nonsteroidal and noncompetitive inhibitor of type I and type II 5alpha
      reductases, (-)-(S)-4-[1-[4-[1-(4-isobutylphenyl) butoxy]benzoyl]indolizin-3
      yl]butyric acid (TF-505), after single and multiple oral doses in healthy
      volunteers. METHODS: In the single-dose study, six young adult males in each dose
      group received 25 mg or 50 mg of TF-505, and six older males (>or= 40 years) in
      each dose group received 75 mg or 100 mg of TF-505. The subjects were given the
      drug in ascending dose and in the fasting state. Six subjects also received 50 mg
      of TF-505 after breakfast in a two-period crossover manner. In the multiple-dose
      study, six older males in each dose group received 12.5 mg or 25 mg TF-505 after
      breakfast daily for 7 days. Plasma concentrations of TF-505, dihydrotestosterone
      (DHT) and testosterone were measured. The pharmacokinetics of TF-505 were
      analysed by a compartment model with first-order absorption, first-order
      elimination and a lag time. Pharmacokinetic and pharmacodynamic relationships
      were evaluated by indirect response modelling with inhibition of input. RESULTS:
      Maximum plasma concentration (Cmax) and the area under the concentration-time
      curve (AUC) increased proportionately after the single dose up to 50 mg and with
      the multiple doses. Linearity was not detected between 75 and 100 mg of TF-505.
      Dose dependency was also noted for the effect of TF-505 on DHT concentrations
      following single doses up to 50 mg and multiple doses. Plasma DHT concentrations
      decreased maximally to 58.2, 49.5, 54.2 and 49.8% of basal values at 8-12 h after
      single administration of 25, 50, 75 and 100 mg TF-505, respectively, and to 60.5
      and 49.4% at the 7th and 5th dose following multiple doses of 12.5 and 25 mg TF
      505, respectively. The predicted effect curves matched the observed data when the
      indirect response model was applied to the time course of the suppressant effect
      of TF-505 on plasma DHT concentrations after both the single and multiple
      studies. Fifty percent inhibitory concentrations (IC50) of 0.82, 1.48, 1.31 and
      0.88 micro g ml(-1), zero-order rate constants for the onset of plasma DHT
      concentration changes (kin) of 17.8, 17.4, 17.0 and 10.7% h(-1) and first-order
      rate constants for increase in plasma DHT concentrations to basal values (kout)
      of 0.17, 0.16, 0.17 and 0.10 h(-1) for the single study at doses of 25, 50, 75
      and 100 mg, respectively, were attained. In the multiple-dose study, IC50s were
      1.74 and 1.49 micro g ml(-1) for the 12.5 and 25 mg doses, respectively. No
      serious adverse events related to TF-505 were observed. CONCLUSIONS: TF-505 was
      well tolerated in healthy male volunteers. Accumulation of TF-505 in plasma was
      not observed during multiple dosing. The indirect response model described the
      relationships between pharmacokinetics and pharmacodynamics of TF-505. Such
      modelling is expected to yield an appropriate dosage regimen in subsequent
      clinical trials.

PMID- 12236850
TI  - Involvement of CYP2C9 and UGT2B7 in the metabolism of zaltoprofen, a nonsteroidal
      anti-inflammatory drug, and its lack of clinically significant CYP inhibition
      potential.
AB  - AIMS: To identify the cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT)
      isoforms responsible for the formation of the primary metabolite(s) of
      zaltoprofen, and to predict possible drug interactions by investigating the
      inhibition of CYP isoforms in vitro. METHODS: The metabolism of zaltoprofen was
      studied in vitro using recombinant CYP and UGT isoform cDNA-expression systems.
      The effects of selective isoform inhibitors on zaltoprofen metabolism were
      studied using human liver microsomes. The inhibitory effects of zaltoprofen on
      the metabolism of selective probe substrates for CYP1A2, CYP2C9, CYP2C19, CYP2D6,
      CYP2E1 and CYP3A4 were also determined in human liver microsomes. RESULTS:
      Zaltoprofen was extensively metabolized by CYP2C9 and UGT2B7. CYP2C9 catalysed
      sulphoxidation but not hydroxylation of zaltoprofen. In the human liver
      microsomal metabolism study, zaltoprofen metabolism was markedly inhibited by
      sulphaphenazole, a selective inhibitor of CYP2C9. In the drug interaction study,
      negligible inhibition (< 15%) of the activities of CYP1A2, CYP2C19, CYP2D6,
      CYP2E1 and CYP3A4 was apparent at 5 micro g ml(-1), the maximum plasma
      concentration observed in humans after oral administration of an 80 mg
      zaltoprofen tablet. However, zaltoprofen inhibited CYP2C9 by 26% at 5 micro g ml(
      1). At higher concentrations, zaltoprofen produced some inhibition of CYP2C9
      (IC50 = 19.2 micro g ml(-1); 64.4 micro m) and CYP3A4 (IC50 = 53.9 micro g ml(
      1); 181 micro m). The free drug concentrations in plasma (0.02 micro g ml(-1),
      67.0 nm) at the Cmax of the clinically effective doses are much lower than the
      IC50 values corrected for the nonspecific binding ratio of zaltoprofen to
      microsomal protein (15.5 micro g ml(-1) for CYP3A4, 49.5 micro g ml(-1) for
      CYP3A4). Furthermore, the maximum free drug concentrations in the hepatic
      intracellular was calculated to be 0.068 micro g ml(-1) and the increase in the
      AUC in the presence of zaltoprofen was estimated to be only 0.4% for CYP2C9
      substrates and 0.1% for CYP3A4 substrates, respectively. CONCLUSIONS: Zaltoprofen
      is predominantly metabolized by CYP2C9 and UGT2B7, and is considered unlikely to
      cause significant drug interactions in vivo when coadministered with CYP
      substrates at clinically effective doses.

PMID- 12236851
TI  - Absence of an interaction between the synthetic pentasaccharide fondaparinux and
      oral warfarin.
AB  - AIMS: To investigate the pharmacokinetic and pharmacodynamic interaction of the
      antithrombotic pentasaccharide fondaparinux (Org31540/SR90107A), given
      subcutaneously, and oral warfarin in healthy subjects. METHODS: This study was
      performed according to a randomised, three-way cross-over, placebo-controlled,
      double-blind design in 12 healthy male subjects. The treatment consisted of five
      subcutaneous (s.c.) injections of fondaparinux (4 mg) or placebo at 24 h
      intervals. Oral dosing of warfarin or placebo was added to the fourth (15 mg) and
      fifth (10 mg) s.c. injection. Blood samples for pentasaccharide assay, PT and
      APTT were drawn before the first s.c. dose of the pentasaccharide and over a 6
      day period thereafter. RESULTS: Fondaparinux administered to healthy male
      volunteers alone or in combination with oral warfarin was well tolerated and no
      serious adverse events were observed. No differences were found in the AUC (43 vs
      44 mg l(-1) h), Cmax (645 vs 678 ng ml(-1)) or elimination half-life (13.8 vs
      14.1 h) of fondaparinux between the pentasaccharide-only and the combination
      treatment. The effect of warfarin on PT (mean maximal increase: 8.2 s.) was not
      influenced by the presence of the pentasaccharide (mean maximal increase in PT:
      9.1 s.). After all treatments a small rise in APTT was seen. No further
      differences could be detected in the pharmacodynamic parameters following the
      three treatments. CONCLUSIONS: The coadministration of warfarin did not influence
      the pharmacokinetics of fondaparinux in healthy subjects. PT can still be used to
      monitor the effect of oral anticoagulants during the switch from antithrombotic
      treatment with pentasaccharide to full oral anticoagulant therapy.

PMID- 12236852
TI  - Pharmacodynamic interaction between the new selective cholesterol absorption
      inhibitor ezetimibe and simvastatin.
AB  - AIMS: The primary aims of these two single-centre, randomized, evaluator-blind,
      placebo/positive-controlled, parallel-group studies were to evaluate the
      potential for pharmacodynamic and pharmacokinetic interaction between ezetimibe
      0.25, 1, or 10 mg and simvastatin 10 mg (Study 1), and a pharmacodynamic
      interaction between ezetimibe 10 mg and simvastatin 20 mg (Study 2). Evaluation
      of the tolerance of the coadministration of ezetimibe and simvastatin was a
      secondary objective. METHODS: Eighty-two healthy men with low-density lipoprotein
      cholesterol (LDL-C) >or=130 mg dl-1 received study drug once daily in the morning
      for 14 days. In Study 1 (n=58), five groups of 11-12 subjects received
      simvastatin 10 mg alone, or with ezetimibe 0.25, 1, or 10 mg or placebo. In Study
      2 (n=24), three groups of eight subjects received simvastatin 20 mg alone,
      ezetimibe 10 mg alone, or the combination. Blood samples were collected to
      measure serum lipids in both studies. Steady-state pharmacokinetics of
      simvastatin and its beta-hydroxy metabolite were evaluated in Study 1 only.
      RESULTS: In both studies, reported side-effects were generally mild, nonspecific,
      and similar among treatment groups. In Study 1, there were no indications of
      pharmacokinetic interactions between simvastatin and ezetimibe. All active
      treatments caused statistically significant (P<0.01) decreases in LDL-C
      concentration vs placebo from baseline to day 14. The coadministration of
      ezetimibe and simvastatin caused a dose-dependent reduction in LDL-C and total
      cholesterol, with no apparent effect on high-density lipoprotein cholesterol (HDL
      C) or triglycerides. The coadministration of ezetimibe 10 mg and simvastatin 10
      mg or 20 mg caused a statistically (P<0.01) greater percentage reduction (mean 
      17%, 95% CI -27.7, -6.2, and -18%, -28.4, -7.4, respectively) in LDL-C than
      simvastatin alone. CONCLUSIONS: The coadministration of ezetimibe at doses up to
      10 mg with simvastatin 10 or 20 mg daily was well tolerated and caused a
      significant additive reduction in LDL-C compared with simvastatin alone.
      Additional clinical studies to assess the efficacy and safety of coadministration
      of ezetimibe and simvastatin are warranted.

PMID- 12236853
TI  - Dose-response relationships between individual nonaspirin nonsteroidal anti
      inflammatory drugs (NANSAIDs) and serious upper gastrointestinal bleeding: a meta
      analysis based on individual patient data.
AB  - AIMS: To define by amalgamation of data obtained in contemporaneous case-control
      studies, the risks associated with individual nonaspirin nonsteroidal anti
      inflammatory drugs (NANSAIDs) according to doses used. METHODS: Meta-analysis of
      individual patient data from three retrospective case-control studies using
      similar data collection protocols was carried out in hospitals in Catalonia,
      England, Scotland and Sweden. 2472 cases of upper gastrointestinal bleeding and
      5877 controls were studied. Main outcome measures were risks associated with
      individual NANSAIDs according to dose used and the period of time for which they
      were given. RESULTS: Ibuprofen showed the lowest odds ratio (OR = 1.7; 95%
      confidence interval 1.1, 2.5), followed by diclofenac (4.9; 3.3, 7.1),
      indomethacin (6.0; 3.6, 10.0), naproxen (9.1; 6.0-13.7), piroxicam (13.1; 7.9
      21.8) and ketoprofen (34.9; 12.7, 96.5). Striking dose-response relationships
      were seen with four to eight-fold increases in risk within conventionally used
      dose ranges for all except ketoprofen, where numbers were too few to allow dose
      analysis. Across the class, risk was highest during the first week of use (11.7;
      6.5, 21.0), decreased thereafter with continuing use (5.6; 4.6, 7.0), and fell to
      3.2 (2.1, 5.1) 1 week after discontinuing use. Concurrent use of more than one
      NANSAID substantially increased risk. CONCLUSIONS: The risk of upper
      gastrointestinal bleeding with NANSAIDs varies twenty-fold depending on the drug,
      and by three to seven-fold depending on the dose chosen. Risk is maximal during
      the first week and decreases thereafter. Paracetamol (acetaminophen) is not
      associated with upper gastrointestinal bleeding at any dose and should be the
      first-line analgesic wherever possible.

PMID- 12236854
TI  - Use of nonsteroidal anti-inflammatory drugs and the risk of first-time acute
      myocardial infarction.
AB  - AIMS: Aspirin decreases the risk of clinical manifestations of atherothrombosis.
      This effect is mainly due to inhibition of platelet aggregation and potentially
      due to anti-inflammatory properties of aspirin. To evaluate whether use of non
      aspirin non-steroidal anti-inflammatory drugs (NSAIDs) may also be associated
      with a decreased risk of first-time acute myocardial infarction (AMI), we
      performed a population-based case-control analysis using the United Kingdom-based
      General Practice Research Database (GPRD) METHODS: We identified first-time AMI
      patients free of preexisting diagnosed cardiovascular or metabolic diseases. We
      compared use of NSAIDs prior to the index date between cases and control patients
      who were matched to cases on age, gender, practice and calendar time. RESULTS: A
      total of 3319 cases (<or=75 years) with a diagnosis of first-time AMI between
      1992 and 1997 and 13139 controls (matched to cases on age, sex, general practice
      attended, calendar time, years of prior history in the GPRD) were included.
      Overall, the relative risk estimate of AMI (adjusted for smoking, body mass
      index, hormone replacement therapy and aspirin) in current NSAID users was 1.17
      (95% CI 0.99, 1.37). Long-term current NSAID use (>or=30 prescriptions) yielded
      an adjusted odds ratio (OR) of 1.20 (95% CI 0.94, 1.55). Stratification by age
      (<65 years vs>or=65 years) and sex did not materially change the results.
      CONCLUSIONS: Our findings indicate that current NSAID exposure in patients free
      of diagnosed cardiovascular or metabolic conditions predisposing to
      cardiovascular diseases does not decrease the risk of AMI.

PMID- 12236855
TI  - Double injection vs skin microdialysis technique in minimally invasive in vivo
      pharmacology.

PMID- 12236856
TI  - Cyclosporin enhances the tendency towards oedema and flushing noted on
      dihydropyridine calcium channel blockers.

PMID- 12236857
TI  - Spontaneous reporting of adverse drug reactions in Cuba: integrating continuous
      education, training and research in a network approach.

PMID- 12236861
TI  - Introduction to the exotic and laboratory animal issue.

PMID- 12236862
TI  - Viewpoint - laboratory animal ophthalmology.

PMID- 12236863
TI  - Bilateral eyelid agenesis repair in a captive Texas cougar.
AB  - Bilateral eyelid agenesis was presented with multiple ocular anomalies in a
      captive Texas cougar (Felis concolor). Corneal exposure resulted in substantial
      keratoconjunctivitis and blepharospasm. Bilateral inferopapillary fundic
      colobomas, persistent pupillary membranes, and an atypical iris coloboma OD were
      present. Surgical repair with a rotational pedicle flap resulted in functionally
      effective eyelids. Trichiasis was later treated with cryotherapy. Eyelid agenesis
      is reported infrequently in domestic cats and among large felids has only been
      reported in the snow leopard.

PMID- 12236864
TI  - Vecuronium bromide, phenylephrine and atropine combinations as mydriatics in
      juvenile double-crested cormorants (Phalacrocorax auritus).
AB  - Topical vecuronium bromide (Norcuron) and combinations with atropine and
      phenylephrine, were evaluated as mydriatics in juvenile double-crested cormorants
      (Phalacrocorax auritus). Nine cormorants were treated with each of four
      protocols: 1% atropine; 4 mg/mL vecuronium bromide (total 0.16 mg/eye); atropine
      with vecuronium; and atropine, 2.5% phenylephrine, followed by vecuronium. Drugs
      were applied topically at 15-min intervals (0.01 mL/drop). Pupil diameter was
      measured manually every 15 min with a pupil gauge calibrated to the nearest 0.5
      mm. No effect was observed with atropine alone. Average +/- SD peak pupil
      diameter for vecuronium, atropine/vecuronium, and
      atropine/phenylephrine/vecuronium were 5.4 +/- 1.1 mm, 5.7 +/- 0.8 mm and 6.2 +/-
      0.4 mm, respectively; and duration of peak diameters were 38 +/- 28 min, 79 +/-
      71 min and 103 +/- 58 min, respectively. The combined atropine, phenylephrine and
      vecuronium provided the most consistent dilation with larger average pupil size
      and longer average duration. No side-effects from vecuronium were observed in
      these birds.

PMID- 12236865
TI  - Vasculature of the ophthalmic rete in night herons (Nycticorax nycticorax):
      scanning electron microscopy of corrosion casts.
AB  - Vasculature of the ophthalmic rete (rete ophthalmicum) in the night heron
      (Nycticorax nycticorax) was studied using scanning electron microscopy of
      vascular corrosion casts and light microscopy on tissue sections. Most blood to
      the eyeball and a lesser volume of blood to the brain passed through the
      ophthalmic rete via the external ophthalmic artery. The collateral retial
      arterioles originated from the external ophthalmic artery forming a flat and
      fusiform-shaped arterial network at the ventrotemporal region of the eyeball. The
      arterial network was intermixed with a similar complex of the veins from the eye.
      The ophthalmotemporal artery, which supplied the eyeball posteriorly, and
      supraorbital and infraorbital arteries, which supplied the eyeball anteriorly,
      originated from the rete. Blood from the eye, which is a site of potential heat
      loss, drained into the ophthalmic rete via the ophthalmotemporal vein. On the
      casts of retial arterioles, slit-like cleavages at branching sites representing
      flap valves, which might play a role as sluice valves, were seen. In addition,
      marks of circularly running grooves, which might represent tufts of smooth muscle
      cells and might contribute to a sphincter activity, were observed. These
      anatomical specializations of the avian ophthalmic rete, involving parallel
      arrangement of arteries and veins, may function to facilitate counter-current
      heat exchange and to regulate blood pressure and volume to the eye and the brain.

PMID- 12236866
TI  - Unilateral exophthalmia in a European hedgehog (Erinaceus europaeus) caused by a
      lacrimal ductal carcinoma.
AB  - A 5-year-old European hedgehog was examined because of exophthalmos of the left
      eye. A retrobulbar mass in the ventromedial orbit was suspected and confirmed by
      a computed tomography scan. Exophthalmos progressed despite systemic broad
      spectrum antibiotic therapy. The left orbit was exenterated and the mass was
      partially removed. The histopathologic diagnosis was lacrimal ductal carcinoma.
      Lacrimal ductal carcinoma is rare in humans and animals. The long-term prognosis
      is guarded to poor.

PMID- 12236867
TI  - Veterinary ophthalmology in laboratory animal studies.
AB  - In this overview the current status of the role of veterinary ophthalmology in
      laboratory animal studies is discussed. Attention is devoted to current
      regulatory requirements and study construction, examination techniques commonly
      used in studies, and a consideration of species characteristics that may be
      important to investigators. Methods for recording data are discussed with
      examples of recording systems.

PMID- 12236868
TI  - Spontaneous cataracts in laboratory rabbits.
AB  - OBJECTIVE: To document the occurrence and incidence of spontaneously occurring
      cataracts in older New Zealand White (NZW) and New Zealand White x New Zealand
      Red (NZW x NZR - F1) rabbits during prescreening examinations at Alcon
      Laboratories. PROCEDURES: A retrospective study was conducted on prescreening
      examination records of NZW and NZW x NZR (F1) rabbits at Alcon Laboratories
      between April 1999 and May 2001. RESULTS: A total of 946 rabbits (670 NZW and 276
      NZW x NZR) ranging in age from 77 to 288 days were examined. Of the NZW rabbits,
      333 were males and 337 were females. Of the NZW x NZR (F1) rabbits, 139 were
      males and 137 were females. Thirty-eight NZW rabbits (23 males and 15 females)
      exhibited immature cataracts in one or both eyes, and three NZW x NZR (F1)
      rabbits (one male and two females) exhibited cataracts in one or both eyes. The
      overall incidence of cataracts was 4.3% of all rabbits. Males and females were
      equally affected, but a significant difference in the incidence of cataracts
      existed between the NZW and NZW x NZR (F1) rabbits with 5.7% of the NZW rabbits
      affected and 1.1% of the NZW x NZR (F1) rabbits affected. CONCLUSION: Spontaneous
      juvenile cataracts occur in rabbits and may develop as incidental lesions during
      toxicologic studies. The incidence of cataracts noted in our studies is
      consistent with an autosomal recessive mode of inheritance, but further studies
      are needed to confirm the mode or modes of inheritance. Hybrid pigmented rabbits
      (F1 or NZW x NZR) exhibited a significantly lower incidence of cataracts.

PMID- 12236869
TI  - Ocular disease in rats: a review.
AB  - The rat Rattus norvegicus is widely used in experimental work, both providing a
      rodent model for human ocular disease and as a species for toxicologic screening.
      In addition, the rat is more and more widely kept as a pet, being both friendly
      and intelligent. Diagnosis and treatment of ocular disease is important for the
      welfare of individual animals and whole colonies, but also to ensure that
      spontaneous disease is not compromising experimental work. Here, ophthalmic
      conditions are reviewed in order to provide a survey of ocular disease in the rat
      both for veterinary ophthalmologists and for laboratory animal veterinarians and
      research workers.

PMID- 12236870
TI  - Examination of the rat eye at the early stage of development with osmium
      tetroxide staining.
AB  - This communication describes the benefit of osmium tetroxide (OsO4) staining on
      the examination of the eye during the early stage of organogenesis of rat
      embryos. The embryos were obtained by laparotomy on embryonic day 12 (ED 12) and
      were stained with OsO4 for examination of the ocular tissues with a binocular
      stereo-microscope, light microscope and scanning electron microscope. At the
      binocular stereo-microscopic level, the invaginated lens placode, lens pit and
      optic cup were clearly distinguished. The osmium-stained lens placode and the
      optic cup were light brown and dark brown in color, respectively. Light
      microscopic examination revealed that OsO4 postfixation could provide superior
      paraffin-embedded embryonic sections. Scanning electron microscopic examination
      revealed the lens pit as a round opening between the lateral nasal prominence and
      maxillary prominence. Thus, a rapid technique by which the ocular tissues of rat
      embryos can be examined under a binocular stereo-microscope was developed. This
      OsO4 staining method will provide a useful tool for research on organogenesis and
      ocular development.

PMID- 12236871
TI  - Multiple ocular colobomas in the snow leopard (Uncia uncia).
AB  - Two singleton female snow leopard cubs are reported with bilateral central upper
      lid colobomas. In addition, one cub had a coloboma of the fundus in one eye
      extending from the lower optic disc region. Surgical treatment by wedge resection
      was successful in both cases. Details of ocular colobomas in other snow leopards
      reported in the literature are described and it is suggested that the exact
      etiology of the condition in this species may be discovered by further study of
      similar colobomas in the domestic cat.

PMID- 12236872
TI  - Penetrating keratoplasty for treatment of corneal protrusion in a great horned
      owl (Bubo virginianus).
AB  - A young adult great horned owl (Bubo virginianus) was examined following presumed
      trauma. The owl had soft tissue injury to its left wing as well as corneal
      protrusion, lens subluxation, and iridodialysis of the right eye. The bird's eye
      was treated surgically with a large, rectangular penetrating keratoplasty.
      Following escape from housing, the bird was found with partial wound dehiscence
      and iris prolapse 12 days post operation. Surgical repair was performed and
      healing progressed for 14 days, at which time the transplant dehisced and the
      globe was exenterated. The patient rehabilitated well until escaping from its
      cage again 4 weeks later, at which time it sustained an open comminuted humeral
      fracture and was euthanized.

PMID- 12236873
TI  - Phacoemulsification in an adult Savannah monitor lizard.
AB  - An adult male Savannah monitor lizard (Varanus exanthematicus) was presented for
      bilateral lens opacities that had progressed rapidly over the previous 2 months.
      A diagnosis of bilateral mature cataracts was made and phacoemulsification
      cataract extraction was performed. Surgery restored vision and normal activity to
      the patient.

PMID- 12236874
TI  - Phacoemulsification for the management of Encephalitozoon cuniculi-induced
      phacoclastic uveitis in a rabbit.
AB  - Phacoemulsification was performed on a New Zealand White rabbit with slowly
      progressive unilateral phacoclastic uveitis and cataract formation. The
      irrigating solution with lenticular contents were centrifuged and examined
      cytologically using Weber's chromotrope-based stain. Microsporidial spores were
      observed and positively identified as Encephalitozoon cuniculi via polymerase
      chain reaction. More than 1 year following surgical therapy, the rabbit is visual
      and comfortable without medications.

PMID- 12236875
TI  - Squamous cell carcinoma associated with a periorbital mass in a veiled chameleon
      (Chamaeleo calyptratus).
AB  - This report describes a squamous cell carcinoma in a 1-year-old female veiled
      chameleon (Chamaeleo calyptratus). The lesion developed as a small (1 by 1 mm)
      left periocular discoloration of a scale never involving the eye. The mass was
      first diagnosed as an abscess, increased in size (4 by 8 by 3 mm), and recurred
      after two surgical resections combined with antibiotic therapy. Poor nutritional
      condition and egg production by the chameleon complicated management of this
      condition. The mass was removed surgically a third time at which point
      histopathologic evaluation revealed a locally invasive squamous cell carcinoma.
      Bacterial culture of the mass isolated a pure culture of Pseudomonas aeruginosa.
      Ceftazidime was administered at 20 mg/kg IM every 48 h for 20 days. The animal
      died 3 months later from complications during an ovariohysterectomy for pregnancy
      toxemia and oviduct inertia. Necropsy showed no local recurrence or metastasis of
      the tumor.

PMID- 12236876
TI  - Bilateral neuroepithelial choristomas of the optic disc in a cynomolgus monkey
      (Macaca fascicularis): a case report.
AB  - A 6-year-old intact male cynomolgus monkey of Chinese origin was received at the
      Sierra Biomedical Facility. While physical examination revealed good body
      condition with no abnormalities, routine ophthalmic examination revealed
      bilateral proliferative optic neuropathy involving the dorsal aspect of the optic
      disc. No changes were noted in the appearance of the lesions over 8 months, and
      fluoroescein angiography revealed no abnormalities other than obstruction of the
      view of the retinal vessels by the lesions. Histopathologic studies revealed
      characteristics consistent with a diagnosis of bilateral neuroepithelial
      choristoma.

PMID- 12236877
TI  - Taenia serialis causing exophthalmos in a pet rabbit.
AB  - A 16-month-old, male, neuter Dwarf Lop rabbit presented with exophthalmos of the
      right eye of 3 weeks duration. Under sedation an ultrasound of the right eye was
      performed and showed an orbital hypo-echoic area posterior and ventrolateral to
      the right globe, which was presumed to be a cyst. Fine needle aspirate removed
      5.5 mLs of straw-colored fluid from the cyst, which allowed the globe to return
      to its normal position. Two months later the rabbit re-presented with
      exophthalmos of the right eye. Exploratory surgery was performed and a large
      cystic structure was removed from the ventro-lateral conjunctival fornix.
      Histology confirmed the cyst to be a coenurus of Taenia serialis.

PMID- 12236879
TI  - Transitional cell carcinoma metastatic to the eye in a collared peccary (Tayassu
      tajacu).
AB  - A 15-year-old female collared peccary (Tayassu tajacu) was presented for
      ophthalmic examination following sudden onset of blindness. Bilateral retinal
      detachment was diagnosed, neoplasia suspected, and euthanasia performed.
      Widespread tumor dissemination was apparent at autopsy, and transitional cell
      carcinoma was diagnosed histologically. The tumor was identified as arising from
      the ovary. Epidemiologic features of this case are discussed.

PMID- 12236878
TI  - Dacryops in a red-eared slider (Chrysemys scripta elegans): case report.
AB  - Clinical and histologic findings of an orbital lacrimal cyst (dacryops) in a 23
      year-old-female red-eared slider (Chrysemys scripta elegans) are described. Main
      ophthalmologic findings included unilateral exophthalmus, engorged episcleral
      vessels, periocular swelling superior to the globe, incomplete lid closure, and
      reduced ocular motility. Based on sonographic and cytologic examination of the
      tissue, the preliminary diagnosis of an orbital cyst was established. After
      surgical resection of the cystic structure, the eye remained visual but
      enophthalmic. Histopathologic diagnosis of the resected tissue was interstitial
      dacryoadenitis.

PMID- 12236880
TI  - Fluorouracil as a treatment for corneal papilloma in a Malayan tapir.
AB  - A 26-year-old, wild caught, male Malayan tapir at the Miami Metrozoo with
      bilateral corneal papillomas was serially immobilized and given subconjunctival
      injections of fluorouracil. Over the course of 17 weeks five bilateral injections
      of 25 mg fluorouracil were given. This treatment caused regression of the corneal
      lesions as evidenced by decreased lesion diameter, decreased corneal vascularity,
      increased corneal clarity, and improved visual function. No adverse drug effects
      were observed.

PMID- 12236881
TI  - Conjunctival dermoid in two guinea pigs: a case report.
AB  - Clinical and histologic findings of conjunctival dermoids in two unrelated guinea
      pigs are described. The dermoids were treated surgically by resection with
      superficial lamellar keratectomy and corneal epithelial debridement.
      Histologically the dermis underneath a stratified squamous keratinized and
      variably pigmented epithelium consisted of multiple hair follicles, with clearly
      visible arrectores pilorum muscles, sebaceous glands and loose vascularized fatty
      tissue.

PMID- 12236882
TI  - Investigation of basal cell carcinoma [correction of carcionoma] by confocal
      laser scanning microscopy in vivo.
AB  - BACKGROUND/PURPOSE: In vivo confocal laser scanning microscopy (CLSM) allows to
      study human skin up to 200 micro m deep non-invasively. Aim of this study was to
      investigate basal cell carcinoma (BCC) using in vivo CLSM, and to compare the
      micromorphologic features of BCC with uninvolved skin. METHODS: Twelve patients
      with histological diagnosis of BCC referred to our department for tumor excision
      were investigated on the lesion(s) and on clinically uninvolved sites
      preoperatively by in vivo CLSM using the Vivascope 1000 (Lucid Inc., Rochester,
      USA). The images were compared to histological examinations of the excised
      tissue. RESULTS: Typical changes in vasculature such as increase in number and
      diameter of the blood vessels, loss of the vascular architecture, parallelly and
      horizontally orientated vessels, and accumulation and rolling phenomena of bright
      reflecting cells of 11.88 +/- 1.75 micro m in diameter along the vessel wall were
      observed in all BCCs. The tumor stroma of the BCCs showed a strong reflectance
      mainly due to numerous bundles of collagen fibers encoating dark, cell-rich areas
      of tumor parenchym. In five patients, slim basaloid cells with relatively large,
      elongated dark nuclei were observed in the periphery of the tumor parenchym. In
      the fibrosing type of BCC, curled bundles of collagen with large cells
      represented the tumor stroma. CONCLUSIONS: BCC can be investigated by CLSM and
      provide typical features. Besides the tumor parenchym and stroma, typical changes
      in vasculature seem to be a sensitive criteria for BCC and may in future help in
      diagnosing BCC by CLSM as well as in assessing the margins of large tumors. We
      suggest that CLSM is a promising non-invasive tool for the diagnostics of BCC and
      the assessment of tumor margins prior to surgery.

PMID- 12236883
TI  - Influence of age on the wrinkling capacities of skin.
AB  - BACKGROUND: Comparisons of clinical assessment with measurement of physical
      parameters are rare. OBJECTIVE: To standardize the horizontal wrinkling of the
      skin in order to define a reference chart of the different wrinkling grades and
      to propose an interpretation of the clinical pattern in terms of skin layers
      thickness and mechanical parameters. METHODS: A device allowing reproducible
      wrinkling of the skin was made. The skin folds created in this way were
      clinically assessed on women of different ages. Measurements of the mechanical
      properties of the skin were carried out by using a Torquemeter. Skin layers'
      thicknesses were measured by using in vivo Confocal Microscopy (CM) and
      Ultrasound Imaging (B mode). RESULTS: Skin wrinkling grades increase versus age.
      Skin elasticity, extensibility and echogenicity decrease also versus age and the
      wrinkling grade. Wrinkling appears to be related to skin rigidification (for both
      stratum corneum and dermis) coupled to a certain weakening of the upper dermis
      (loss of echogenicity). CONCLUSION: This study points out the key role of the age
      related alterations of the upper dermis in skin wrinkling capacities.

PMID- 12236884
TI  - The character of eyelashes and the choice of mascara in Korean women.
AB  - BACKGROUND/AIMS: Skin care products based on the skin type and sensitivity have
      been successfully appealed in cosmetics market, but there has been few researches
      related with the character of customer in the field of make-up product including
      mascara. The aim of this study is to analyse and classify the eyelashes of Korean
      women objectively and to find out the relationship between individual eyelash
      character and expecting mascara-effect. METHODS: For 50 Korean women in their
      twenties to thirties, 12 parameters related to shape of eyelashes were
      investigated using image analysis system with digital camera. The experimental
      data were compared with the subjects' perception and questionnaire to determine
      the tendency of mascara was performed on same panels. Subjects were classified
      and the relation between the shape of eyelashes and need for mascara was
      investigated by statistical procedure. RESULTS: Average length of centre section
      (ALCS), covering ratio (CR) and curl-up angle (CA) were the numerical parameters
      that can represent the length, thickness and curling of subjects' eyelashes,
      respectively. Subjects were classified into 6 clusters (I approximately VI) by
      the similarity of above three parameters using cluster analysis method. Cluster I
      approximately III were characterized as the short and thin eyelashes with a
      preference for long-lash effect and complaint about staining of lower-eyelid in
      the use of mascara. Cluster IV approximately VI had the long and thick eyelashes
      with preference for volume-up effect of mascara and complaint about cleaving of
      eyelashes. Subjects had five sorts of preference patterns about mascara-effects
      and those patterns were highly related with the shape of their eyelashes.
      CONCLUSION: Image analysis system and statistical procedure were the useful
      methods in characterizing the shape of eyelash and finding the objective criteria
      for classification of eyelashes. Because shape of eyelash turned out to be one of
      the most important factors that can influence the need and complaint of subjects
      about mascara in this study, the consideration of shape of eyelashes is
      recommended in the development of mascara which can satisfy the customers'
      demand.

PMID- 12236885
TI  - Split face study on the cutaneous tensile effect of 2-dimethylaminoethanol
      (deanol) gel.
AB  - BACKGROUND/AIMS: Beyond subjective assessments, the effect of skin tensors is
      difficult to assess. The present 2-phase randomized double-blind split face study
      was designed to compare the effect of a gel containing 3% 2-dimethylaminoethanol
      (deanol, DMAE) with the same formulation without DMAE. METHODS: In a first pilot
      study, sensorial assessments and measures of the skin distension under suction
      were performed in eight volunteers. In a second study conducted in 30 volunteers,
      shear wave propagation was measured. RESULTS: Large interindividual variations
      precluded any significant finding in the first study. The DMAE formulation
      showed, however, a significant effect characterized by increased shear wave
      velocity in the direction where the mechanical anisotropy of skin showed
      looseness. CONCLUSION: The DMAE formulation under investigation increased skin
      firmness.

PMID- 12236886
TI  - Evaluation of facial skin type by sebum secretion: discrepancies between
      subjective descriptions and sebum secretion.
AB  - BACKGROUND/AIMS: Facial skin is usually classified as dry, normal, and oily in
      the cosmetics field. However, there is no standard objective method for
      classifying facial skin. METHODS: We measured sebum excretion with Sebumeter at
      four sites on the face. Based on the amount of sebum secretion, we reclassified
      skin type according to the guidelines provided by the manufacturer. The mean of
      sebum excretion (mean facial sebum excretion; MFSE) was also calculated. RESULTS:
      People secrete varying amounts of sebum at different skin sites. Reclassification
      of skin type based on sebum secretion revealed that most participants
      underestimated the amount of facial sebum excretion. When sebum secretion amounts
      were compared, a statistically significant difference was apparent between the
      oily and dry skin types. However, there were no statistical differences between
      oily and normal, and normal and dry skin. CONCLUSION: We showed that subjective
      skin type does not match the amount of sebum secreted. Thus, this simple and
      subjective classification is of very limited use and it should be re-evaluated by
      using an objective and standardized measuring tool.

PMID- 12236887
TI  - Assessment of collagen lattice thickness by B-scan echography.
AB  - BACKGROUND/AIMS: Collagen lattices are an in vitro dermal equivalent that has led
      to the development of an original model of dermal tissue. Fibroblasts cultured in
      three-dimensions in a collagen matrix differentiate similarly to in vivo. New
      technological performances in ultrasonic imaging can now provide precise
      measurements of tissue thickness with good resolution. The aim of this study was
      to assess, by B-scan echography, the correlation between collagen lattice
      thickness and various collagen and cell concentrations. METHODS: Three
      concentrations of human dermal fibroblasts (F1 = 8.10(5)C/mL, F2 = 16.10(5)C/mL,
      F3 = 32.10(5)C/mL) and three concentrations of rat tail collagen (C1 = 2 mg mL(
      1), C2 = 3 mg mL(-1), C3 = 4 mg mL(-1)) were prepared for five different kinds of
      collagen lattices: F(2)C(1), F(2)C(2), F(2)C(3), F(1)C(1) and F(3)C(1) (n = 5 per
      case). Ultrasonic imaging was performed on day 0, 4, 6, 10, 12 and 14 using a
      Dermcup 2020 scanner. The scans measured thickness in the centre and periphery of
      the lattice. RESULTS: The collagen lattice echogenicity was similar to a dermis
      in vivo. For each assessment, the collagen lattice thickness increased until day
      12 and then stabilized. The lattice was thicker when the cellular concentration
      was higher, (at day 14: F(1C1) = 0.66 mm, F(2C1) = 0.86 mm, F(3C1) = 1.21 mm).
      The collagen concentration did not significantly influence lattice thickness.
      CONCLUSION: Collagen lattice thickness increased with retraction time and
      cellular concentration.

PMID- 12236888
TI  - The dynamics of transepidermal water loss (TEWL) from hydrated skin.
AB  - BACKGROUND/AIMS: When an occlusive cover is applied on the skin, the
      transepidermal water loss (TEWL) is inhibited and the skin moisturises. Upon the
      removal of the occlusion the water, which accumulated in the skin porosity during
      the occlusion, evaporates and diffuses outside showing a TEWL rate larger than
      the basal value, and function of time. The aim of this paper is to develop a
      physical-mathematical model for simulating the dynamics of Epidermal (free-)
      Water Evaporation (EWE) and of transepidermal water loss of hydrated skin.
      METHODS/RESULTS: The model, which is based on general results and methods of
      transport phenomena, has been calibrated and validated by experimental tests, in
      vivo, with the use of an evaporimeter. Both the theoretical model and the
      experimental results show that the release of excess water that accumulates in
      the skin following an occlusion, is a fast transient phenomenon, which has a
      characteristic time of the order of minutes (the initial decay is very rapid
      indeed, in less than a minute the TEWL value may decrease by more than 50%). On
      the other hand, the characteristic measuring time of the evaporimeter may be as
      large as 30 s. Therefore, as shown in the paper, the use of the evaporimeter for
      measuring the initial values of TEWL upon immediate removal of the occlusion is
      not reliable. When a transient phenomenon cannot be fully described by a
      measuring device that has an initial characteristic response time of the order of
      the characteristic time of the phenomenon, a mathematical model, which describes
      the dynamics of the phenomenon must be developed. Then the measurements taken
      after the measuring device is stabilised may be extrapolated to the initial times
      by the use of the model, thus allowing a full quantitative description of the
      phenomenon vs. time. Finally, the experimental results show that a baby's
      disposable diaper, when loaded with water, behaves like an impermeable occlusive
      cover on the skin.

PMID- 12236889
TI  - A non-invasive tape absorption method for recovery of inflammatory mediators to
      differentiate normal from compromised scalp conditions.
AB  - BACKGROUND/AIMS: A simple non-invasive tape (Sebutape) adsorption method was used
      to recover inflammatory proteins from normal and compromised human scalp (i.e.
      dandruff and seborrheic dermatitis) in order to assess the inflammatory and
      immunologic changes relevant to these clinical conditions. METHODS: The scalps of
      subjects identified by a dermatologist as having either dandruff (n = 18),
      seborrheic dermatitis (n = 19) or normal scalp (n = 16) were visually graded to
      obtain total adherent scalp flaking scores (TASFS). Sebutape samples were then
      collected from both the high and low TASFS scalp sites using a one-minute tape
      application. To recover inflammatory molecules, tapes were extracted in buffered
      saline with sonication and the tape extracts analysed using commercial
      immunoassay methods for pro-inflammatory cytokines [i.e. interleukin-1alpha (IL
      1alpha), IL-1beta, IL-1 receptor antagonist (IL-1ra), IL-8 and tumor necrosis
      factor-alpha (TNF-alpha)] and the immunologic cytokines [i.e. IL-2, IL-4, IL-10,
      IL-12, IL-15 and interferon gamma (IFN-gamma)]. Nitric oxide (NO) was also
      assayed on tape extracts using the Greiss reaction. To account for differences in
      protein loading on the tapes all cytokine and NO results were normalized using
      the total protein (TP) amounts recovered in tape extracts. RESULTS: The IL
      1alpha/TP levels recovered from dandruff and seborrheic scalps were significantly
      decreased (P = 0.03) compared to normal appearing scalp levels. The scalp levels
      of IL-1ra/TP and the ratio of IL-ra to IL-1alpha were significantly (P = 0.002)
      or directionally (P = 0.07) higher in seborrheic dermatitis scalps and dandruff
      scalps, respectively, compared to normal scalps. The IL-1ra and the IL-1ra/IL
      1alpha ratio values correlated well with the TASFS. The TNF-alpha/TP levels
      recovered from dandruff scalps were significantly higher (P = 0.02) than levels
      recovered from seborrheic dermatitis and normal scalp subjects. IL-2/TP was
      significantly increased (P = 0.01) and IFN-gamma and NO significantly decreased
      (P = 0.05) in the seborrheic dermatitis scalp samples compared to normal
      controls. CONCLUSION: The Sebutape method has proven useful for distinguishing
      normal from diseased scalp conditions. The cytokines recovered from the scalp
      tape samples showed distinct patterns that differentiated dandruff, seborrheic
      dermatitis and normal scalp populations. These methods may also prove useful for
      monitoring the clinical efficacy of therapeutic actives for treating dandruff and
      seborrhea.

PMID- 12236890
TI  - Variation of skin properties within human forearms demonstrated by non-invasive
      detection and multi-way analysis.
AB  - BACKGROUND/AIM: It is known that the properties of human skin vary locally. The
      purpose of this study was to investigate the properties of human volar forearms
      even further using advanced non-invasive techniques and numerical methods.
      METHODS: The skin properties of human volar forearms were investigated using
      measurements of trans epidermal water loss and multifrequency electrical
      impedance. Eight sites on the forearms of 27 healthy volunteers were measured.
      The sites were oriented as squares, four sites on both left and right forearm,
      approximately 40-50 mm apart. RESULTS: Analysis of variance showed significant
      differences for epidermal water loss (P < 0.01) and the skin impedance (P <
      0.001) between the inner and outer sides of the arms. Additionally, parallel
      factor analysis of the full skin impedance spectra also showed that there are
      systematic differences between right and left arm (P < 0.01). CONCLUSION: It is
      crucial to design skin studies carefully in order to minimise the effects of the
      local skin properties of human skin.

PMID- 12236891
TI  - Controversies in periodontology.

PMID- 12236892
TI  - Classifying periodontal diseases--a long-standing dilemma.

PMID- 12236893
TI  - Noninflammatory destructive periodontal disease (NDPD).

PMID- 12236894
TI  - Beneficial bacteria of the periodontium.

PMID- 12236895
TI  - Periodontitis-systemic disease associations in the presence of smoking--causal or
      coincidental?

PMID- 12236896
TI  - In or out: the invasiveness of oral bacteria.

PMID- 12236897
TI  - Periodontal epithelium: a newly recognized role in health and disease.

PMID- 12236898
TI  - Finding genetic risk factors for periodontal diseases: is the climb worth the
      view?

PMID- 12236899
TI  - The role of stress in inflammatory disease, including periodontal disease: review
      of concepts and current findings.

PMID- 12236900
TI  - Trends in periodontal care.

PMID- 12236901
TI  - Restoration or implant placement: a growing treatment planning quandary.

PMID- 12236902
TI  - The periodontal-endodontic controversy.

PMID- 12236904
TI  - Severe renal bleeding caused by a ruptured renal sheath: case report of a rare
      complication of percutaneous nephrolithotomy.
AB  - BACKGROUND: Percutaneous nephrolithotomy is a minimally invasive intervention for
      renal stone disease. Complications, which are rare and usually presented as case
      reports, are diversified as the utilization of the procedure is expanded. The
      procedure causes less blood loss and less morbidity when compared to open
      surgical procedures. Yet, there are some reports involving severe bleeding and
      relevant morbidity during surgery. These are usually related with the surgical
      technique or experience of the surgeon. Renal sheaths are designed to cause
      minimal trauma inside the kidney and, to our knowledge, there are no reports
      presenting the rupture of a sheath causing severe bleeding during the procedure.
      CASE REPORT: We present an adult patient who had severe bleeding during
      percutaneous nephrolithotomy due to parenchymal injury caused by a ruptured renal
      sheath. During retrieval, due probably to rough handling of the equipment, a
      piece of stone with serrated edges ruptured the tip of the sheath, and this tip
      caused damage inside the kidney. The operation was terminated and measures were
      taken to control bleeding. The patient was transfused with a total of 1600 ml of
      blood, and the stones were cleared in a second look operation. CONCLUSION:
      Although considered to be a minimally invasive procedure, some unexpected
      complications may arise during percutaneous nephrolithotomy. After being
      fragmanted, stone pieces may damage surgical equipment, causing acute and severe
      harm to the kidney. Surgeons must manipulate the equipment with fine and careful
      movements in order to prevent this situation.

PMID- 12236905
TI  - Self-medication and non-doctor prescription practices in Pokhara valley, Western
      Nepal: a questionnaire-based study.
AB  - BACKGROUND: Self-medication and non-doctor prescribing of drugs is common in
      developing countries. Complementary and alternative medications, especially
      herbs, are also commonly used. There are few studies on the use of these
      medications in Pokhara Valley, Western Nepal. METHODS: Previously briefed seventh
      semester medical students, using a semi-structured questionnaire, carried out the
      study on 142 respondents. Demographic information and information on drugs used
      for self-medication or prescribed by a non-allopathic doctor were collected.
      RESULTS: Seventy-six respondents (54%) were aged between 20 to 39 years. The
      majority of the respondents (72 %) stayed within 30 minutes walking distance of a
      health post/medical store. 59% of these respondents had taken some form of self
      medication in the 6-month period preceding the study. The common reasons given
      for self-medication were mild illness, previous experience of treating a similar
      illness, and non-availability of health personnel. 70% of respondents were
      prescribed allopathic drugs by a non-allopathic doctor. The compounder and health
      assistant were common sources of medicines. Paracetamol and antimicrobials were
      the drugs most commonly prescribed. A significantly higher proportion of young
      (<40 years) male respondents had used self-medication than other groups.
      CONCLUSIONS: Self-medication and non-doctor prescribing are common in the Pokhara
      valley. In addition to allopathic drugs, herbal remedies were also commonly used
      for self-medication. Drugs, especially antimicrobials, were not taken for the
      proper duration. Education to help patients decide on the appropriateness of self
      medication is required.

PMID- 12236906
TI  - [The supervision of the PET].

PMID- 12236908
TI  - [Methodological aspects related to the determination of the relative renal
      function using 99mTC MAG3].
AB  - The aim of the study was to evaluate three different methods for calculating the
      split renal function in patients with only one functioning kidney, keeping in
      mind that the split function should be zero on the side of the non-functioning
      kidney. PATIENTS: We retrospectively selected 28 99mTc MAG3 renograms performed
      in children, 12 with unilateral nephrectomy, 4 with unilateral agenesis and 12
      with a non-functioning kidney. METHODS: A renal and perirenal region of interest
      (ROI) were delineated around the functioning kidney. The ROIs around the empty
      kidney were drawn symmetrically to the contralateral side. The split renal
      function was calculated using three different methods, the integral method, the
      slope method and the Patlak-Rutland algorithm. RESULTS: For the whole group of 28
      kidneys as well as for the three categories of patients, the three methods
      provided a split function on the side of the non-functioning kidney close to the
      zero value, regardless of whether the empty kidney was the left or the right one.
      CONCLUSION: We recommend the use of the integral method for the whole range of
      split renal function with 99mTc MAG3. No significant improvement was obtained by
      means of the more sophisticated Patlak-Rutland method.

PMID- 12236907
TI  - [CYFRA 21.1 cytosol levels in lung adenocarcinomas. Correlation with other
      clinico-biological parameters].
AB  - INTRODUCTION: Cyfra 21.1 are soluble cytokeratin 19 fragments present in several
      biological fluids. The aim of this work was to study cyfra 21.1 cytosolic levels
      in lung adenocarcinomas and their possible correlation with other clinical
      biological parameters. PATIENTS AND METHODS: Cyfra 21.1 was determined, using an
      immunoradiometric assay (CIS BioInternational. France), in 58 tissue samples of
      lung adenocarcinomas patients. Other parameters included in the study were the
      following: clinical stage, histological grade, ploidy, S-phase cellular fraction,
      as well as cathepsin D, CA 125 and hyaluronic acid levels in cytosols. Likewise,
      AH, erbB2 oncoprotein, CD44s, CD44v5 and CD44v6 levels in cell surfaces were
      assayed. RESULTS: Cyfra 21.1 cytosolic levels oscillated between 24.8 and 6,774
      ng/mg prot. (median 1,147.5) and were higher (p:0.00074) than those observed in
      16 normal lung samples of the same patients. We did not observe any statistically
      significant differences in cyfra 21.1 values when clinical stage, ploidy, S-phase
      and histological grade were considered. When lung adenocarcinomas were classified
      according to cyfra 21.1 positivity, using 1,499 ng/mg prot. as cut-off, which
      represents the 75th percentile of the whole group, we noted that positive cases
      had higher levels of cathepsin D (p:0.00218), cytosolic hyaluronic acid
      (p:0.02947), erbB2 protein (p:0.06272) and CA 125 (p:0.07243) than negative
      carcinomas. CONCLUSIONS: These results suggest the possibility that high
      cytosolic cyfra 21.1 levels could be associated with a poor outcome in lung
      adenocarcinomas.

PMID- 12236909
TI  - [Fast method of labelling leukocytes with 99mTc HM PAO].
AB  - OBJECTIVE: To modify the method of labelling leukocytes with 99mTc HM-PAO by
      centrifuging 15 minutes at low gravity (g) instead of sedimentation at a variable
      time (30-90 minutes) to obtain leukocytic rich plasma (LRP). METHODS: The g
      number recovering the greatest number of leukocytes was determined. The cellular
      composition of LRP obtained by centrifugation and sedimentation was analyzed.
      Lastly, labelling results in two groups of patients (p) were compared: one group
      of 118 p using the traditional sedimentation method (SM) and another of 124 p
      using the proposed centrifugation alternative (CM). RESULTS: Centrifugation at
      5xg produced the greatest recovery of leukocytes (93.1 5.1%). No significant
      difference was observed in leukocyte recovery in LRP obtained either by
      centrifugation or by sedimentation. However, red blood cell contamination was
      greater in centrifugation (12.8 4.9 x 108) than in sedimentation (7.7 3.5 x 108)
      (p < 0.0001). The comparison of the SM and the CM gave the following results:The
      number of leukocytes recovered in both methods was similar (73.9 15.1% vs 76.5
      12.7%) with approximately the same platelet contamination (8.0 6.2 vs 8.4 6.5%).
      The number of red blood cell contaminants per leukocyte was 3.0 1.0 for the MS
      and 5.1 2.6 for the MC (p < 0.001). Labelling yield (LY) was somewhat higher for
      the CM (57.8 11.9%) than for the SM (50.8 12.6%) as a result of greater red blood
      cell contamination and superior radiochemical purity of the 99mTc HM-PAO used in
      the labelling by CM (90,9 5,9%) with regard to the SM (87.9 9.5%). No difference
      was observed in the scintigraphic images obtained with either of the methods,
      given the scarce uptake of the radiopharmaceutical by the red blood cells (3-7%)
      in comparison with the leukocyte uptake (70-90%). CONCLUSION: The proposed MC
      considerably reduces the labelling time of leukocytes with 99mTc HM-PAO without
      affecting the quality of scintigraphic images and represents an important
      labelling alternative of great interest to the Radiopharmacy Units of Nuclear
      Medicine Services.

PMID- 12236910
TI  - [Comparative study of CEA antibody scan and computed tomography scan in the
      follow-up of patients with colorectal cancer].
AB  - OBJECTIVE: To assess the utility of nuclear imaging with labelled monoclonal
      antibody against CEA immu-4 Fab' (CEA-scan) and the computed tomography (CT) in
      the follow-up of colorectal cancer after therapy and his accuracy in the
      detection of recurrent disease. MATERIALS AND METHODS: 48 studies underwent to 45
      patients (25 men and 20 women) with an average age of 64, diagnosed and treated
      of colorectal cancer, 5 hours after the intravenous administration of 1.25 mg of
      arcitumomab (CEA-scan) labelled with 945 MBq of 99mTc. The reasons to request the
      CEA-scan were signs compatible with active disease in 15 cases, post-therapy
      control in asyntomatic patients in 17 and suspicious of recurrence in 16.
      Histological confirmation of the lesions was obtained in 12 patients and the rest
      was assessed by an average of evolution time of 26 months, CT and blood CEA
      levels. RESULTS: The values of sensitivity, specificity, PPV and NPV obtained for
      the CEA- scan were of 91%, 76%, 77% y 90% respectively; 78%, 80%, 78% y 80%
      respectively for the CT and 65%, 42%, 88% y 74% respectively for the blood CEA
      levels. The CEA-scan and blood CEA levels combination showed the best results
      100%, 95%, 93% y 100% respectively. CONCLUSION: We did not find any correlation
      between blood CEA levels and CEA-scan results. The CEA-scan showed the highest
      sensitivity an NPV. The combination of different techniques showed better results
      than an individual valoration.

PMID- 12236912
TI  - [Scientigraphic hot lesions secondary to osseous metastases in a patient with
      multiple myeloma].
AB  - The myeloma bone deposits may be normal or may also appear as areas of a low
      uptake on the bone scintigraphy; the presence of multiple hot lesions with
      negative X-ray and minimal CT findings in patients with multiple myeloma being
      very uncommon. We reported the case of a 68 year old woman suffering from a
      multiple myeloma with multiple and hot metastatic lesions in bone scintigraphy.
      The X-ray was negative and the CT-findings only demonstrated a lytic femoral
      lesion, the spinal osseous dissemination being confirmed by MRI. We believe that
      this is an interesting work due to the rarity of the scintigraphic pattern as
      well as the discussion carried out on the radionuclide imaging methods in the
      diagnosis of myeloma-related bone lesions.

PMID- 12236911
TI  - [Chronic infections multifocal osteomyelitis vs chronic recurrent multifocal
      osteomyelitis: with reference to one case].
AB  - We present a rare case of chronic infectious multifocal osteomyelitis with
      affectation symmetric in the both femures in a patient with spondyarthropathic
      secondary Inflammatory Bowel Disease. The diagnosis was confirmed with culture of
      the bone biopsy. The aim of this work is the revision of the Chronic Infectious
      Multifocal Osteomyelitis and the Chronic Recurrent Multifocal Osteomyelitis into
      SAPHO syndrome that both were the possibilities diagnoses.

PMID- 12236913
TI  - [Frostbite of the upper and lower limbs in an expert mountain climber: the value
      of bone scan in the prediction of amputation level].
AB  - A 38 year old man was admitted to our hospital 10 days after suffering a
      frostbite injury in hands and feet while practicing mountain climbing, at 8,100
      meters of altitude, while he was trying to reach the top of the K2 mountain. A
      99mTc-MDP bone scan performed in aseptic conditions showed: in hands: absence of
      bone uptake in the 3rd phalanx and distal portion of 2nd phalanx of the 5th
      finger of the left hand, and multiple areas of increased uptake in the distal
      portion of both hands. In feet: uptake decreases in the 2nd phalanx of the first
      toe of the left foot, and absence of bone uptake in the 3rd phalanx of the 2nd
      toe of the left foot, and in 2nd phalanx of the 1st toe and 3rd phalanx of the
      2nd, 3rd and 4th toes of the right foot. As in the hands, there were multiple
      areas of increased uptake in the distal portion of both feet. The phalanges with
      absence of bone uptake had to be amputated, while those that presented increased
      uptake recovered with conservative treatment. Bone scan is indicated in the
      evaluation of frostbite injuries and helps to establish the prognosis early.

PMID- 12236914
TI  - [PET in neurology and psychiatry I. PET with FDG in the study of the CNS].

PMID- 12236916
TI  - [Beyond blood pressure reduction in the treatment of arterial hypertension.
      Clinical implications of the LIFE study].
AB  - To date, blood-pressure lowering has been the main therapeutic objective in
      patients with arterial hypertension, regardless of the drug used, except for
      drugs selected for accompanying conditions. The LIFE study, carried out in 9,193
      high-risk hypertensive patients (with ECG criteria of left ventricular
      hypertrophy), has shown that a therapeutic regimen based on losartan combined
      with a thiazide was accompanied by a significant reduction in the risk of
      cardiovascular complications in more than 90% of patients compared with atenolol
      and a thiazide over a mean follow-up period of 4.8 years. The incidence of the
      primary endpoints (cardiovascular death, stroke, and myocardial infarction) was
      11% in the losartan group and 13% in the atenolol group (13% relative risk
      reduction, p = 0.021). Losartan therapy was associated with more benefits in
      stroke risk reduction and in the development of new cases of diabetes. In the
      analysis of the subgroup of 1,195 patients with hypertension and diabetes
      included in the LIFE study, losartan had a special prognostic benefit. One of the
      cardiovascular events included as a primary endpoint was observed in 18% of the
      losartan-treated patients and in 23% of the atenolol-treated patients (24%
      relative risk reduction, p = 0.031). The LIFE trial showed that losartan produced
      better cardiovascular protection than atenolol, a similar blood pressure
      reduction, and was better tolerated. This drug seems to confer extra
      cardiovascular protection in addition to reducing blood pressure.

PMID- 12236917
TI  - [Collaborate either multi-disciplinarily, trans-disciplinarily or inter
      disciplinarily, and please advance together].

PMID- 12236918
TI  - [Ventricular septal defect with aortic regurgitation. An unsolved problem].

PMID- 12236919
TI  - [Interdisciplinarity of Spanish cardiovascular research teams].
AB  - OBJECTIVES: The incidence of interdisciplinarity (ID) in Spanish cardiovascular
      research teams was analyzed and scientists' opinions about interdisciplinary
      relationships were examined. METHODS: The data analyzed were obtained in a survey
      sent in 1999 to a sample of 310 researchers. They were selected using
      bibliometric techniques and/or for being research project leaders in recent
      years. RESULTS: The response rate was 61%. Data were obtained from 130 research
      teams located mainly in Madrid and Catalonia. Teams doing clinical research (81%)
      and those working in hospitals (64%) predominated. Different facets of the
      interdisciplinary nature of the teams were analyzed: scientist training, team
      composition, behavior patterns, collaboration, and publication and reading
      habits. A high ID was observed in the area: more than 70% of the teams are
      interdisciplinary according to the training of scientists, around 80% make use of
      knowledge or techniques from other disciplines, and around 90% read and publish
      in journals outside their own disciplines. Basic research teams had a higher ID
      than clinical ones. A total of 37 highly interdisciplinary teams were identified.
      These teams had a greater tendency towards collaboration. CONCLUSIONS:
      Interdisciplinary reading and publishing habits were the norm among Spanish
      researchers, even in single-discipline groups. The scattered nature of teams,
      their high rate of external collaborations, and the multidisciplinary context of
      centers enhance interdisciplinary relationships. Administrative barriers do not
      seem to be a major obstacle to establishing interdisciplinary contacts.

PMID- 12236920
TI  - [Utility of the serum biochemical markers CPK, CPK MB mass, myoglobin, and
      cardiac troponin T in a chest pain unit. Which marker determinations should be
      requested and when?].
AB  - BACKGROUND: The prognostic value of biochemical markers in relation to time since
      onset of chest pain was evaluated in an emergency room with a chest pain unit.
      METHODS: In a single-center, prospective study we included 321 consecutive
      patients admitted to the emergency room with suspected unstable angina IIIB and
      an evolution of less than 12 hours. Blood samples were collected for CPK, CPK MB
      mass, myoglobin, and cardiac troponin T assays 6, 12, and 18 h after the onset of
      pain. ROC curve analysis was carried out to compare biochemical markers in terms
      of cutoff values and time since onset of pain. We determined the relation between
      prognosis and biochemical markers before and after adjustment for baseline
      characteristics. RESULTS: CPK mass and myoglobin showed the maximum sensitivity
      and specificity for new ischemic recurrences 6 hours after the onset of chest
      pain with laboratory cutoff values. We had to wait 12 h after the onset of pain
      for troponin T to be useful using the laboratory cutoff value (0.1 ng/ml). A
      single determination 6 hours after onset of chest pain of cardiac troponin T
      above 0.04 ng/ml was the most sensitive and specific marker for new ischemic
      recurrences. CONCLUSIONS: A single blood determination of cardiac troponin T 6
      hours after the onset of chest pain complete the prognostic stratification in
      combination with clinical and ECG variables. The best cutoff point of cardiac
      troponin T, based on univariate and multivariate analysis, was 0.04 ng/ml 6 h
      after the onset of chest pain.

PMID- 12236921
TI  - [Prognostic factors in unstable angina with dynamic electrocardiographic changes.
      Value of fibrinogen].
AB  - INTRODUCTION AND OBJECTIVES: The prognosis of unstable angina varies between
      series depending on the inclusion criteria and management protocol used. The aim
      of this study was to analyze in-hospital events and their predictors in a
      homogeneous single-center series of patients with unstable angina. MATERIAL AND
      METHODS: A total of 246 patients with the following inclusion criteria were
      studied: 1) resting anginal pain, 2) transient electrocardiographic changes
      during anginal pain, 3) normal CK-MB levels and 4) exclusion of postinfarction
      angina. All patients were treated with aspirin and enoxaparin (1 mg/kg/12 h).
      Coronary angiography was performed in the case of recurrent angina or ischemia in
      Bruce I-II stage during the predischarge effort stress test. The variables
      recorded were risk factors, history of ischemic heart disease, history of
      coronary surgery, ECG upon admission, and fibrinogen. RESULTS: During the
      hospital stay the following events were recorded: 36% recurrent angina, 58%
      cardiac catheterization, and 5,7% major events (infarction or death).
      Multivariate analysis found recurrent angina to be more frequent in patients with
      a history of coronary bypass surgery (p = 0.004. OR = 22; CI 95%, 3-182), ST
      segment changes (p = 0.01. OR = 4.7, CI 95%; 1.4-15.9) and higher fibrinogen (p =
      0.002. OR = 1,4, CI 95%; 1.1-1.7). Fibrinogen was the only variable related to
      cardiac catheterization (p = 0,009. OR = 1.3. CI 95%, 1.1-1.6) and major events
      (p = 0.001. OR = 2.0. CI 95%, 1.4-3.1). CONCLUSIONS: 1) Unstable angina with
      electrocardiographic changes was associated to a high rate of in-hospital events.
      2) Fibrinogen was related to any event, and previous by-pass surgery and ST
      changes were related to recurrent angina.

PMID- 12236922
TI  - [Brachial artery flow-mediated dilation in healthy men, men with risk factors,
      and men with acute myocardial infarction. Importance of occlusion-cuff position].
AB  - INTRODUCTION AND OBJECTIVES: Flow-mediated dilation (FMD) is endothelium
      dependent and can be assessed by ultrasound in the brachial artery. We sought to
      determine the most suitable position for the occlusion cuff for the study of FMD
      in three groups of adult men. SUBJECTS AND METHODS: We included 160 subjects,
      mean age 58.5 7.8 years: 40 healthy subjects, 80 with cardiovascular risk
      factors, and 40 patients with AMI. In a subgroup of 60 subjects, the first 10,
      30, and 20 of each group, respectively, FMD was evaluated twice, after upper arm
      occlusion and forearm occlusion to induce hyperemia. RESULTS: In the initial
      substudy, the FMD after upper arm occlusion was 7.6 2.4% in healthy subjects, 5.1
      2.2% in men with risk factors (p < 0.0001), and 3.5 2.2% in AMI patients (p <
      0.041, with respect to the risk-factor group). FMD after forearm occlusion was
      4.6 1.5%, 2.3 2.1% (p < 0.006), and 2.2 1.9%, respectively, with no significant
      statistical differences between the risk-factor and AMI groups. Only upper arm
      occlusion was performed in the remaining participants, as planned, because it
      provided the most accurate information. Overall, the FMD was, respectively, 7.8
      3.1%, 5 2.6% (p < 0.0001) and 3.3 3% (p < 0.004, with respect to the risk-factor
      group). FMD was directly related to HDL cholesterol and inversely related to
      resting diameter and number of risk factors. CONCLUSION: The best approach to
      studying FMD is proximal occlusion since it allows for a better stratification of
      the with endothelial dysfunction. With this technique, a worsening of endothelial
      function in acute myocardial infarction can be demonstrated.

PMID- 12236924
TI  - [Permanent atrial fibrillation in heart disease in Spain. The CARDIOTENS study
      1999].
AB  - INTRODUCTION AND OBJECTIVE: Atrial fibrillation is the most common arrhythmia
      seen in clinical practice. The objective of this study was to know the frequency
      of atrial fibrillation and the characteristics of patients with atrial
      fibrillation in the Cardiotens study. MATERIAL AND METHOD: A cross-section study
      with systematic selection of the study sample. All 32,051 outpatients seen on the
      same day by 1,159 physicians specialized in primary-care (79%) and cardiology
      (21%) were prospectively added to a database including history of cardiac disease
      (heart failure, coronary disease or atrial fibrillation), blood pressure, and
      ongoing treatment. RESULTS: Atrial fibrillation was present in 25% of patients
      with previous cardiovascular disease (6,194 patients), the prevalence being 4.8%
      (1,540/32,051) of the study population. Atrial fibrillation was more frequent in
      females 29%, (810/2,837) than in males, 22% (730/3,367), p < 0.005). Atrial
      fibrillation was present in 33% (469/1,420) of patients with heart failure and in
      12% (387/3,226) of those with coronary heart disease. Arterial hypertension was
      diagnosed in 25% of the patients with atrial fibrillation. Only 33% of them were
      treated with oral anticoagulants (41% of the patients seen by cardiologists and
      26% by primary-care physicians, p < 0.005). The antiarrhythmic drug most often
      used was digoxin (36%). CONCLUSIONS: Atrial fibrillation had the same frequency
      and epidemiology in Spain as in other Western countries. Antithrombotic therapy
      is underused by primary-care physicians and cardiologists.

PMID- 12236923
TI  - [Aortic valve complications associated with subarterial infundibular ventricular
      septal defect. Echocardiograpic follow-up].
AB  - INTRODUCTION AND OBJECTIVES: Interventricular fibromuscular septal defects of the
      outlet tract are subarterial infundibular ventricular septal defects (VSDs). This
      anatomical situation predisposes to aortic cusp prolapse (AoP) and/or
      regurgitation (AoR). METHODS: In order to determinate the frequency of VSDs and
      the presence or development of aortic valve alterations detected by two
      dimensional echocardiography, we studied 35 patients with VSDs. The defect area
      and presence, severity, and evolution of AoP and/or AoR were evaluated. Ten
      anatomic specimens were studied to verify the echocardiographic correlation.
      RESULTS: Subarterial infundibular defect was present in 6.9% of all ventricular
      septal defects. The average age at time of diagnosis was 5,8 years. VSDs diameter
      and gradient did not change during follow-up. At time of diagnosis, 30 patients
      (87%) did not have AoR, but during an average follow-up of 8 years, 11 (32%)
      developed it. By the end of the study, 46% had AoR. When the time to progression
      of AoR was compared in the group that developed it versus the group that did not,
      the median values were similar in both groups. There was a greater tendency to
      development and/or progression of regurgitation in small VSDs. The echo-anatomic
      correlation was precise. CONCLUSIONS: Aortic valve damage was a frequent finding
      in VSD. Most cases did not progress to more severe AoR. Small VSDs developed more
      severe regurgitation in less time. Surgery must be considered when AoR is
      detected. Regular evaluation by echocardiography is important in follow-up.

PMID- 12236925
TI  - [Surgical closure of atrial septal defect before or after the age of 25 years.
      Comparison with the natural history of unoperated patients].
AB  - INTRODUCTION: Surgical closure of an atrial septal defect (ASD) before the age of
      25 years has been demonstrated to reduce complications during adulthood. However,
      the outcome for patients operated after the age of 25 is still debated. METHODS:
      In a retrospective study we examined the outcome of early and late surgical
      repair of ASD in adults, as compared with the natural evolution of unoperated
      patients. The study population was 280 patients (mean age 40 18 years) with non
      restrictive ASD: 102 patients (group 1) underwent surgery before the age of 25
      years, 90 patients (group 2) underwent surgery after the age of 25 years, and 88
      unoperated patients were older than 25 years at the time of study (group 3). The
      variables analyzed were left ventricular systolic function, left atrial
      dimensions, systolic pulmonary pressure, right ventricular dimensions, the degree
      of mitral and tricuspid regurgitation, and the prevalence of late atrial
      fibrillation. RESULTS: Left ventricular systolic function and the degree of
      mitral regurgitation were not statistically different between groups. Compared
      with the patients in group 2, the patients in group 1 had a significantly lower
      systolic pulmonary arterial pressure (p < 0.001) and less dilated right ventricle
      (p < 0.001) and left atrium (p < 0.001). The degree of tricuspid regurgitation (p
      < 0.001) and prevalence of atrial fibrillation (p < 0.001) were significantly
      higher in the patients of group 2. Compared with group 3, the patients in group 2
      had a significantly lower systolic pulmonary arterial pressure (p < 0.001) and
      less dilated right ventricle (p < 0.001). However, the left atrial dimensions,
      degree of tricuspid regurgitation, and prevalence of atrial fibrillation did not
      differ in a statistically significant way between the two groups. CONCLUSIONS:
      Surgical repair of an atrial septal defect in patients over 25 years of age does
      not fully prevent hemodynamic deterioration and the development of atrial
      arrhythmias. Therefore it seems that the surgical closure of ASD before adulthood
      should be strongly recommended.

PMID- 12236926
TI  - [Congenital heart disease, heterotaxia and laterality].
AB  - Congenital heart disease occurs in about 0,8% of all newborns. Many cardiac
      malformations occur among relatives and have a polymorphic presentation. The
      origin of most congenital heart disease is thought to be multifactorial, implying
      both anomalous expression of genes and the influence of epigenetic factors.
      However, in a small number of cases, the origin of congenital heart disease has
      been directly related to chromosomal anomalies or to defects in a single gene.
      Curiously, defects in a single gene can explain a polymorphic presentation if the
      anomalous gene controls a basic embryonic process that affects different organs
      in time and space. Some of these genes appear to control the establishment of
      laterality. The establishment of the left-right asymmetry starts at the Hensen
      node. Here, the initial embryonic symmetry is broken by cascades of gene
      activation that confer specific properties on the left and right sides of the
      embryo. Although there are variations between species, some basic patterns of
      gene expression (Nodal, Pitx2) appear to be maintained along the phylogenetic
      scale. Anomalous expression of these genes induces the heterotaxia syndrome,
      which usually courses with congenital heart disease. The development of heart
      malformations is illustrated with the mouse mutant iv/iv, which is a model for
      the heterotaxia syndrome and the associated congenital heart disease.

PMID- 12236927
TI  - [Prevention and treatment of ischemic heart disease in patients with diabetes
      mellitus].
AB  - The incidence of cardiovascular diseases among diabetic patients is so high that
      diabetes mellitus is currently defined as a cardiovascular disease equivalent.
      Furthermore, diabetic patients who develop acute coronary syndromes have a poorer
      short-term and long-term prognosis, so primary and secondary preventive measures
      are critically important in this population subgroup. There is substantial
      evidence that pharmacological therapy for primary and secondary cardiovascular
      prevention is more effective in diabetic patients than in non-diabetics. This
      article reviews the evidence of the efficacy of pharmacological prevention
      therapies in diabetic patients in favor of an aggressive pharmacological
      preventive strategy. Every diabetic patient without known cardiovascular disease
      should be treated with angiotensin-converting enzyme inhibitors and statins. High
      risk patients should also receive low-dose aspirin.Compared with non-diabetics,
      diabetic patients who develop acute coronary events benefit more from the
      addition of intensive antithrombotic therapy to aspirin treatment. Diabetic
      patients presenting with non-ST segment elevation syndromes have better outcomes
      when treated with clopidogrel or glycoprotein IIb/IIIa inhibitors, and diabetics
      presenting with ST-segment elevation or left bundle-branch block have a greater
      survival benefit when given thrombolytic therapy compared with non-diabetic
      patients.Unless formal contraindications are present, diabetic patients with
      ischemic heart disease, particularly those with previous myocardial infarction,
      should always be treated with aspirin, betablockers, angiotensin converting
      enzyme inhibitors, and statins, regardless of lipid levels, left ventricular
      systolic function or the presence of congestive heart failure.

PMID- 12236928
TI  - [Hemolytic anemia secondary to paravalvular regurgitation].

PMID- 12236929
TI  - [Tricuspid stenosis after pacemaker implantation without evidence of bacterial
      endocarditis. A case report].
AB  - Tricuspid stenosis related to endocardial pacemaker leads is uncommon. We report
      the case of a patient with severe tricuspid stenosis documented 15 years after
      the implantation of a permanent DDD pacemaker for symptomatic congenital heart
      block. The atrial and ventricular leads both had a loop at the level of the
      tricuspid valve that may have caused endothelial damage and, eventually,
      tricuspid stenosis.

PMID- 12236930
TI  - [Prognostic value of normal myocardial radionuclide scan in patients with
      positive treadmill test].
AB  - The purpose of this study was to determine the prognostic value of a normal 201Tl
      scan in patients with a positive treadmill exercise stress test. We analyzed
      retrospectively 85 consecutive patients with a positive treadmill exercise test
      and normal Tl201 scan who were studied for the diagnosis of coronary artery
      disease from January 1996 to December 2000. The pretest probability of coronary
      artery disease was intermediate or high in all patients. Seventy-eight patients
      (89%) were followed up for 2.03 years. Forty patients (51%) were men. Age was 56
      years. The cardiac events considered were angina, revascularization, nonfatal
      myocardial infarction, and cardiac death. During the follow-up period, none of
      the patients suffered a major cardiac event. Eight patients had episodes of chest
      pain and one had angor that required revascularization. Patients with an
      intermediate probability of coronary artery disease before the test and normal
      myocardial radionuclide scan had a very good prognosis even with a positive
      treadmill exercise test.

PMID- 12236931
TI  - [Diagnosis of aortic arch thrombosis by two-dimensional echocardiography from the
      jugular fossa in a patient with protein C deficiency].
AB  - We describe the case of a 63-year-old man who suffered concomitant cerebral,
      mesenteric, and renal infarctions. Idiopathic dilated myocardiopathy without
      intracardiac masses was diagnosed by transthoracic echocardiography. A cross
      sectional view of the innominate artery from the jugular fossa notch position
      revealed a threatening thrombus in the proximal region of the aortic arch. Severe
      functional protein C deficiency was diagnosed by hematologic study.

PMID- 12236932
TI  - [Right atrial myxoma in a patient with antiphospholipid antibodies].
AB  - A 28 year-old asymptomatic male with previously detected elevation of
      antiphospholipid antibodies (aPL) had a right atrial mass diagnosed by
      transthoracic echocardiography. Although the morphological characteristics were
      highly suggestive of myxoma, due to the presence of aPL elevation it had to be
      differentiated from atrial thrombus. The patient underwent surgery and a 3 x 4 cm
      mass with its large base attached to the interatrial septum was removed.
      Histopathological examination confirmed that it was a myxoma. On follow-up, the
      patient was asymptomatic and antiphospholipid antibodies became undetectable.

PMID- 12236933
TI  - [Elective cardioversion of atrial fibrillation. Are quinidine and electrical
      shock really equivalent?].

PMID- 12236935
TI  - [Some considerations regarding resistance mechanism to antiretrovirals in HIV
      infection].

PMID- 12236936
TI  - [Relationship between acute phase reactant proteins (APRP) and fatigue during
      post-operative convalescence].
AB  - Surgery originates an inflammatory state which triggers an acute phase response
      (APR). In this study, variations in the acute phase reactant proteins (APRP) and
      their relationship with fatigue were assessed. A total of 58 candidate patients
      for elective abdominal surgery participated in this study. In the preoperative
      period (PRE) and in the post-operative period (9 days [9-P], 27 days [27-P] and
      45 days [45-P]), variations in serum APRP and fatigue were analyzed. In the post
      operative period (9-P), a significant decrease in PT, ALB, PAB, TRF, and an
      increase in CER were observed. In 27-P, significant decreases were observed in
      PAB and PBR, with increased PT and CER, and without significant variations in ALB
      ad TRF. In the 45-P day, a concomitant increase in PT and CER was observed.
      Dynamometric parameters also decreased significantly in the post-operative period
      (9-P). In conclusion, our results demonstrate the existence of changes in serum
      proteins and in APRP after an elective abdominal surgical intervention, which are
      associated with fatigue, evaluated both by subjective and objective (dynamometry)
      means and the use of a mathematical model that considers weight, proteins and
      APRP.

PMID- 12236937
TI  - [Nosocomial bacteremia in the adult patient. Study of associated costs].
AB  - OBJECTIVE: Nosocomial infection causes a prolonged hospital stay and an increase
      in care costs. The objective of this study was to determine the length of stay
      excess and costs attributable to nosocomial bacteremia. PATIENTS AND METHODS:
      Retrospective study of clinical records of 148 patients with nosocomial
      bacteremia during 1996. A matched case-control study was performed. For matching,
      the following parameters were used: RDG, year of admission, age 10 years, main
      diagnosis and number of secondary diagnoses. Costs were determined by excess
      length of hospital stay and calculating alternative costs. RESULTS: Matching was
      obtained for 100 cases (67.5%) and cost estimation was performed. Compared with
      cases, non-matched cases showed differences regarding significant issues for
      cost, such as hospital stay ( p = 0.01), number of empirical (p = 0.001) or
      definitive antibiotics (p = 0.03). The median hospital stay for cases was longer
      than for controls (35 vs 15.5 days, respectively; p = 0.000). When only survivor
      case-control pairs were considered (n = 75), cases remained in hospital for a
      median of 36 vs 15 days for controls (p = 0.000). Hospital stay days attributable
      to nosocomial bacteremia were 19.5 for all matched and 21 for matched survivor
      cases. Only 76% of cases had stay days attributable to bacteremia. Significant
      differences between cases and controls included: the mean total costs of
      admission (p = 0.000), cost of stay (p = 0.001), pharmaceutical expenses (p =
      0.000), and cost of microbiological studies (p = 0.000), laboratory work-up (p =
      0.001) and radiological studies (p = 0.000). Hospital stay represented more than
      60% of costs, followed by pharmaceutical expenses. Cost differences between
      bacteremic patients and controls, calculated in function of stay median, was
      4.424 euros (p = 0.000) and 4.744 euros (p = 0.000) for alternative costs. Ten
      cases showed a difference that represented more than half of the total
      difference. CONCLUSIONS: Nosocomial bacteremia represent a stay prolongation and
      a significant economical burden. Hospital stay and pharmaceutical expenses
      accounted for the most part of the associated costs. The differences in costs
      obtained with both methods were small. Since not all selected cases were matched,
      there may be an error in the appreciation of the difference between cases and
      controls.

PMID- 12236938
TI  - [Acute cerebrovascular accident in the primary antiphospholipid syndrome].
AB  - OBJECTIVE: To report the prevalence of acute cerebrovascular accidents (ACVA) and
      risk factors for thrombosis among patients diagnosed of primary antiphospholipid
      syndrome (PAPLS) and to compare this group with that of patients with PAPLS but
      not ACVA. PATIENTS AND METHODS: Retrospective data analysis of 30 patients
      consecutively diagnosed of PAPLS. Episodes of ACVA were quantitated and other
      cardiovascular risk factors were determined. RESULTS: Thirty percent of patients
      (9/30) had one or more ACVA. No significant differences were found when the
      presence of other cardiovascular risk factors in both groups was compared.
      CONCLUSIONS: Antiphospholipid antibodies in young patients with ACVA should be
      determined, although some other cardiovascular risk factors may coexist.

PMID- 12236939
TI  - [Utility of pravastin in cardiac transplant dyslipidemia].
AB  - Patients undergoing cardiac transplantation are at increased risk of dyslipidemia
      (60% to 80%). Lipid-lowering treatment in these patients should be aggressive
      given the known role of dyslipidemia in chronic transplant rejection. The
      objective of this study was to evaluate the efficacy and safety of pravastatina
      therapy and its effect upon cyclosporine levels in a population of dyslipidemic
      cardiac transplant patients.A total of 20 cardiac transplant patients were
      enrolled in this 39-week length prospective observational study. Patients had
      serum cholesterol levels exceeding 200 mg/dl, and received pravastatin therapy at
      the adequate dose to obtain an optimal lipid profile without significant adverse
      effects. Pravastatin, at a mean dose of 50 18 mg/day, produced a significant
      reduction in total cholesterol levels (from 291 32 to 203 25 mg/dl, p < 0.05),
      LDL cholesterol (from 187 34 to 102 15 mg/dl, p < 0.05) and an increase in HDL
      cholesterol levels (from 48 16 to 55 14, p < 0.05). A slight asymptomatic
      increase in CPK levels was observed but no differences in cyclosporine levels.
      Pravastatin has shown to be an effective and safe therapy in dyslipidemic cardiac
      transplant patients.

PMID- 12236940
TI  - [Current therapy of Helicobacter pylori infection in peptic ulcer disease (first
      part)].

PMID- 12236941
TI  - [Morphology of upper airways in the obstructive sleep apnea syndrome].

PMID- 12236942
TI  - [Intraepithelial lymphocytes in the diagnosis of latent-potential celiac
      disease].

PMID- 12236944
TI  - [Extrapleural lesions and rib notching].

PMID- 12236943
TI  - [Idiopathic inflammatory myopathies].

PMID- 12236945
TI  - [Male patient with a cauliflower-like cutaneous lesion].

PMID- 12236946
TI  - [Sixty-six-year old man with fever, headache and meningeal syndrome].

PMID- 12236947
TI  - [Fever and cervical lymph node enlargement].

PMID- 12236948
TI  - [Pleural effusion in rheumatoid arthritis: a rare presentation].

PMID- 12236949
TI  - [Idiopathic CD4+ T-cell lymphocytopenia associated with disseminated
      cryptococcosis].

PMID- 12236950
TI  - [Bronchiolitis obliterans with organizing pneumonia associated with Mycoplasma
      pneumoniae infection].

PMID- 12236951
TI  - [Treatment of chronic obstructive pulmonary disease].

PMID- 12236953
TI  - [Diseases simulating transitory ischemic attacks or established strokes].

PMID- 12236954
TI  - [Stroke and transient ischemic attack-mimicking conditions: a prospective
      analysis of risk factors and clinical profiles at a general hospital].
AB  - BACKGROUND: Nonvascular structural entities can simulate stroke and transient
      ischemic attacks (TIA) in a variable percentage, but this issue has not been
      properly addressed in our environment. Their differentiation is important, since
      the management of patients with a true cerebrovascular accident differs
      considerably from that of mimicking conditions. OBJECTIVES: To analyze
      prospectively those structural disorders that mimic stroke and TIA in the
      department of neurology of a general hospital and to determine if there are any
      distinctive risk factors and/or clinical presentations that would allow for their
      separation from true stroke and TIA. PATIENTS AND METHOD: All patients admitted
      to our Department of Neurology with stroke or TIA were evaluated prospectively
      for a 4-year period. Those in whom a mimicking condition was disclosed were the
      subjects of this study. Their clinical features and vascular risk factors were
      compared with a sample of randomly selected patients with true stroke or TIA
      admitted during the same period. RESULTS: A total of 28 patients comprised the
      stroke-TIA mimicking group, 21 of them had a stroke-like syndrome and 7 a TIA
      like syndrome. The mimicking group represented a 1.9% (2% of strokes and 1.6% of
      TIA) of all the patients with true cerebrovascular disorders admitted during the
      same period. Cancer, either primary or metastatic, was the single most frequent
      mimicking condition, accounting for two-thirds of the cases. Risk factors for
      stroke and TIA were significantly more frequent in the true stroke-TIA group
      without differences in age or sex, while the opposite is true in terms of prior
      or concurrent cancer. No single clinical profile allowed for a distinction
      between the two groups, although vertebrobasilar dysfunction suggested true
      ischemia, and vomiting, isolated dysarthria and dysarthria-clumsy hand occurred
      only in the true stroke-TIA group. CONCLUSIONS: Nonvascular conditions can cause
      signs and symptoms indistinguishable from true stroke and TIA, representing about
      2% of the patients admitted to a department of neurology with these diagnoses.
      Although there are some differences in clinical presentation and risk factors
      between both groups, neuroimaging studies will be required in the individual
      patient to rule out mimicking conditions.

PMID- 12236955
TI  - [Benign childhood occipital epilepsy: evolution of the occipital spikes].
AB  - PURPOSE: We studied the electro-clinical evolution of the occipital EEG
      discharges characteristic of partial benign epilepsy of childhood with occipital
      paroxysms. The influence of age, sex, epilepsy course and treatment on the
      evolution of this electrical event were analyzed. METHODS: A longitudinal
      retrospective study that included 30 patients who fullfilled the diagnostic
      criteria of benign occipital epilepsy proposed by the ILAE. The onset, migration
      and disappearance of EEG foci were analyzed using the Pearson coefficient and non
      parametric tests. RESULTS: Occipital spikes are found earlier when vomiting is an
      ictal symptom (p < 0.01) or longer seizures (p = 0.05). Patients with and
      antecedent of febrile seizures or with an visual aura show a later onset of
      occipital spikes (p < 0.05). Ictal vomiting is associated with a longer
      persistence of occipital spikes along the years. Migration of EEG foci to
      anterior regions is characteristic of early onset seizures and predicts a later
      remission (p < 0.05). Extraoccipital foci are associated with a high seizure and
      occipital spike recurrence rate. CONCLUSIONS: Occipital spikes persist longer
      than seizures. Ictal vomiting is the only symptom related to specific EEG
      features: early onset, longer evolution and late remission of EEG discharges.

PMID- 12236956
TI  - [Sporadic Creutzfeldt-Jakob disease: phenotypic variability].
AB  - Prion disease are characterized by cerebral deposition of an abnormal protease
      resistant isoform of a membrane-bound glycoprotein called prion protein. Sporadic
      Creutzfeldt-Jakob disease (CJDs) is the most frequent, accounting for
      approximately 85% of all human prion disease. The identification of a new variant
      of Creutzfeldt-Jakob disease has reinforced the need for a detailed analysis of
      phenotypic variability of CJDs. CJDs is typically characterized by rapidly
      progressive dementia, myoclonus, periodic sharp-wave electroencephalographic
      activity, and wide-spread spongiform degeneration. However, variations in
      clinical presentation, disease duration, as well as type and distribution of
      lesion have been consistently observed. The physicochemical properties of PrPsc
      in conjunction with the PRNP codon 129 genotype largely determine this phenotypic
      variability. Continued attention to clinically atypical cases is required to
      monitor the real incidence of CJDs. To reach this goal neuropathological
      examination, including the search for PrPsc, and molecular genetic analysis of
      human prion protein gene (PRNP) should be increasingly applied to atypical
      neurodegenerative diseases.

PMID- 12236957
TI  - [Prevention of recurrent ischemic stroke: recent clinical trial results].
AB  - Clinical trials are providing new insights into long-existing clinical biases for
      the treatment of acute ischemic stroke and prevention of recurrence. The
      structure and completeness of the data sets available for some of the published
      studies have raised controversies about the generality of some of the findings.
      Among these controversies for acute ischemic stroke are whether the benefits of
      so-called low-dose unfractionated heparin exceed or are negated by hemorrhagic
      complications and whether results with heparinoids can be considered a surrogate
      for unfractionated heparin. For prevention of recurrent ischemic stroke, a double
      blind study showed no statically-significant differences for serious hemorrhagic
      complications nor for prevention of recurrence in non-cardioembolic stroke for
      aspirin 325 mg daily against adjusted-dose warfarin with an INR 1.4-2.8, the INR
      value which showed clinical benefit in prevention of first stroke with atrial
      fibrillation. In this study, patent cardiac foramen ovale and antiphospholipid
      antibody status did not predict stroke recurrence. Other platelet antiaggregants
      show varying degrees of reduction in recurrent ischemic stroke compared with
      placebo or aspirin but the recurrent events rates make it difficult to compare
      directly through meta-analysis the results against warfarin. More work on these
      important management issues is justifiable.

PMID- 12236958
TI  - [Klippel-Feil syndrome: unusual iconography].

PMID- 12236959
TI  - [Transient Brown-Sequard syndrome due to spontaneous spinal epidural hematoma].
AB  - Spinal epidural hematoma (SEH) is a low incidence injury. When the cause of
      bleeding is unknown, which occurs in 50% of the cases, we refer to it as
      spontaneous SEH. The clinical presentation is characterized by acute radicular
      pain followed by cord compression syndrome. Brown-Sequard syndrome is exceptional
      as a result of a SEH. Although standard treatment is prompt surgical evacuation
      of the hematoma, spontaneous resolution has also been reported. We present a case
      of spontaneous SEH in a 69 year-old man. An MRI revealed an hematoma in the right
      posterior epidural space extending from C6 to T2. The hematoma was manifested as
      a paresis of the right limbs and sensory loss of the left side below C7 level.
      During the first hours the neurological deficit was improved without treatment
      and consequently a conservative management was continued. After 72 h, the patient
      was completely recovered. We have reviewed the 14 cases of spinal epidural
      hematoma and Brown- Sequard syndrome previously reported, only 2 of them were
      resolved by conservative management. We conclude that when SEH presents as Brown
      Sequard syndrome it usually has a more benign course and that in some cases a
      conservative management can be considered.

PMID- 12236960
TI  - [Postoperative bilateral brachial plexopathy mimicking the "man-in-the-barrel"
      syndrome].
AB  - We describe a patient with a postoperative bilateral upper limb palsy due to
      involvement of the upper trunk of the brachial plexus. The weakness distribution
      (bilateral upper limb paresis without leg involvement) reminded of the classic
      "man-in-the-barrel" syndrome, which is usually due to bilateral watershed
      infarcts of the brain in relation with severe hypotension. Bilateral
      postoperative brachial plexopathies are very uncommon and should be distinguished
      from the "man-in-the-barrel" syndrome of "central" origin, since the former bears
      a much better prognosis and management is different. The mechanisms of plexus
      damage during surgery, as well as the different etiologies of the "man-in-the
      barrel" syndrome, are discussed.

PMID- 12236961
TI  - [Symptomatic hemiparkinsonism with abnormal SPECT in a patient with systemic
      lupus erythematosus (SLE)].

PMID- 12236962
TI  - [Mills syndrome in a young woman receiving oral contraceptives].

PMID- 12236963
TI  - [Sneddon syndrome presenting with dementia].

PMID- 12236967
TI  - [Efficacy and safety of sildenafil in patients with erectile dysfunction and
      hypertension. Prognostic factors].
AB  - BACKGROUND: Our purpose was to assess the efficacy and safety of sildenafil as a
      treatment for erectile dysfunction in hypertensive patients, and to investigate
      those factors associated with a treatment failure. PATIENTS AND METHOD: Open,
      prospective study including 114 patients suffering from erectile dysfunction plus
      arterial hypertension who were evaluated by anamnesis, physical examination,
      blood tests including glycemia and lipidic and hormonal profiles, penile colour
      Doppler ultrasonography after intracavernosal prostaglandin E1 (PGE1) injection,
      and the Sexual Health Inventory for Men (SHIM). Efficacy of sildenafil was
      assessed by administering again the SHIM and by means of a global assessment
      questionnaire. Side effects were also recorded. Factors influencing treatment
      outcome were evaluated by univariate and multivariate statistical analysis.
      RESULTS: Overall, sildenafil was effective in 59.2% of 103 eligible patients.
      Efficacy in patients with psychogenic erectile dysfunction was 75%, whereas in
      those with an organic etiology, the efficacy was 50.7%. Age, diabetes mellitus,
      nocturnal penile tumescence, response to intracavernosal PGE1 injection and
      erectile dysfunction severity (defined by the SHIM basal score) significantly
      influenced treatment response (p < 0.05) after an univariate analysis. The
      multivariate analysis, however, selected only diabetes mellitus and severity of
      erectile dysfunction as the prognostic factors. No severe side effects were
      noticed. CONCLUSIONS: Sildenafil is a rather effective and well-tolerated
      treatment for erectile dysfunction in hypertensive patients. Baseline severity of
      erectile dysfunction and diabetes mellitus represent the prognostic factors most
      significantly associated with treatment outcome.

PMID- 12236968
TI  - [Adherence to antiretroviral therapy measured by pill count and drug serum
      concentrations. Variables associated with a bad adherence].
AB  - BACKGROUND: We aimed at measuring the adherence to HAART by means of pill count
      and drug plasma levels. In addition, we aimed at determining variables associated
      with suboptimal adherence. PATIENTS AND METHOD: Prospective observational study
      of 202 consecutive patients with HIV infection who were receiving antiretroviral
      treatment, followed up during 9 months. At baseline and at the end of the study a
      structured questionnaire was administered and a review of medical charts was
      performed. The adherence was assessed by monthly pill count while drug plasma
      levels were measured every three months. We considered that a patient adherence
      was not fulfilled when the mean pill count was < 90% or when any plasma drug
      level was lower than that expected. RESULTS: Of 143 available patients, 41.2%
      were non-adherent. According to the univariate analysis, non-adherent patients
      were more likely to be younger, female, under a methadone maintenance scheme,
      under psychiatric treatment, to have depression (according to the Beck Depression
      Inventory), to have adverse antiretroviral effects and to have a previous history
      of voluntary withdrawal of the treatment. Men who had sex with other men were
      significantly more adherent. In the multivariate analysis, female sex [OR 2.6
      (1.04-6.65)], to be under a methadone program [OR 9.43 (1.01-88)], to have
      adverse drug effects [OR 2.63 (1.09-6.33)] and to have a previous history of
      voluntary withdrawal [OR 2.63 (1.09-6.36)] were independent risk factors for non
      adherence. CONCLUSIONS: Adherence to antiretroviral therapy was 58.8%, similar to
      that seen in other chronic diseases. To be under a methadone maintenance program
      and having an active drug addiction was related with non-adherence. Women with
      worst adherence levels had frequently psychiatric comorbidity and more adverse
      drug effects.

PMID- 12236969
TI  - [Spectrum of diseases in patients hospitalized with HIV infection in the HAART
      era].
AB  - BACKGROUND: HIV-associated opportunistic infections have changed since the
      introduction of HAART. PATIENTS AND METHOD: We reviewed the clinical records of
      patients with HIV infection admitted in an Infectious Diseases Unit since January
      1996 to December 2001. RESULTS: There were 1.584 hospitalisations in 1.038
      patients (each patient was hospitalised 1,5 times during the study). Most had
      AIDS (66%) and only 28,9% were receiving HAART. Pneumonia (21%) and tuberculosis
      (13%) were the most frequent causes of hospitalisation. Rates of death decreased
      every year. CONCLUSION: Most of HIV infected patients who need hospitalisation do
      not receive HAART, have AIDS and their rate of mortality has decreased.

PMID- 12236970
TI  - [Thromboembolic disease. D dimer: yes or not?].

PMID- 12236971
TI  - [John Snow, double meriatrician].

PMID- 12236972
TI  - [Usefulness of telemedicine in chronic diseases: home tele-care of patient with
      chronic obstructive pulmonary disease].

PMID- 12236974
TI  - [High or excessive resolution?].

PMID- 12236973
TI  - [Treatment failure of acute exacerbations of chronic obstructive airways disease
      risk factors and clinical relevance].

PMID- 12236976
TI  - [Pluriglandular autoimmune syndrome type II associated with essential
      thrombocythemia].

PMID- 12236977
TI  - [Thyroid sarcoidosis in a woman with previous thyroid cancer].

PMID- 12236979
TI  - [Likelihood and odds: some mathematical and linguistic considerations].

PMID- 12236978
TI  - [The Guillain-Barre syndrome due to cytomegalovirus in two siblings. Peak-flow
      meter as the mechanism of transmission].

PMID- 12236980
TI  - [Acute eosinophilic pneumonia as a cause of respiratory failure].

PMID- 12236981
TI  - [HIV seroprevalence among patients attending sexually transmitted clinics in
      Spain, 1998-2000].
AB  - BACKGROUND: Analysis of HIV seroprevalence among patients attending sexually
      transmitted disease (STD) clinic during 1998-2000. METHOD: Unlinked anonymous
      serologic survey among 5,968 patients of seven STD clinics in Spain. RESULTS: HIV
      1 seroprevalence has decreased from 3.7% in 1998 to 1.7% in 2000 (p < 0.0001). In
      2000 it reached 10.6% among homo/bisexual men, 0.4% among sexworkers, and 3.4%
      among other heterosexual categories. Drugs injecting and STD were associated with
      a higher prevalence. CONCLUSIONS: Among people with sexual risk behaviours, STD
      and HIV-infection are strongly associated, and this demonstrates the convenience
      of integrate their attendance.

PMID- 12236982
TI  - [Human herpesvirus-8 detection in Kaposi's sarcoma, multiple myeloma, and
      lymphoproliferative syndromes occurring in immunocompetent and immunocompromised
      patients].
AB  - BACKGROUND: The purposes of this study were: to study the presence of human
      herpesvirus-8 (HHV-8) in different Kaposi's sarcoma (KS) epidemiological groups,
      multiple myeloma (MM), and immunodeficiency-associated lymphoid proliferations;
      to investigate the potential sexual transmission of HHV-8 by analyzing its
      presence in women from the general population, human immunodeficiency virus (HIV)
      seropositive women, and prostitutes; and to establish a reliable and efficient
      PCR strategy for the detection of HHV-8. PATIENTS AND METHODS: HHV-8 detection
      was performed by PCR and positive cases were confirmed by automatic bi
      directional sequencing. We selected 25 KS, 70 immunodeficiency associated non
      Hodgkin's lymphomas (NHL), 30 HIV-positive Hodgkin's lymphomas (HL), and 2
      primary effusion lymphomas (PEL). Bone marrow aspirates were available from 41
      MM, 9 monoclonal gammopathies of undetermined significance and 24 patients with
      other disorders. Bone marrow dendritic cell cultures from 12 MM patients were
      also performed. Cells from cervical, anal, and oral cavity scrapes were examined
      for the presence of HHV-8 in 40 control women, 10 HIV-seropositive women, and 20
      HIV-seronegative prostitutes. Serologic tests were also performed. RESULTS: HHV-8
      was specifically detected in 100% KS and PEL, and in 5.7% immunodeficiency
      associated NHL. All cases of HIV-HL and MM were HHV-8 negative. Antibodies
      against HHV-8 were found in 10% of control women, 10% HIV-positive women, and 25%
      prostitutes. Only 1 sample was positive for HHV-8 by PCR. CONCLUSIONS: HHV-8 is
      associated with all epidemiological forms of KS; HHV-8 does not contribute to the
      pathogenesis of MM, and this virus is not ubiquitous in the human population.
      Seroprevalence of HHV-8 is increased in prostitutes, although this may partially
      be attributed to the geographical origin. For a reliable PCR detection of HHV-8,
      it is necessary to target different regions of the viral genome and to sequence
      amplification products.

PMID- 12236983
TI  - [Analysis of heart rate as a risk factor associated with the progression of
      chronic renal failure].
AB  - BACKGROUND: An increased heart rate is associated with an increased risk of
      cardiovascular and non-cardiovascular death. However, the possible relationship
      between heart rate and the rate of progression of renal disease has not been
      assessed so far. PATIENTS AND METHOD: Twenty-four-hour ambulatory blood pressure
      and heart rate recordings at baseline conditions were obtained in 24 patients
      with non-diabetic chronic renal failure and hypertension. The rate of progression
      of renal disease was estimated on the basis of the slope of the reciprocal of
      serum creatinine concentration against time. RESULTS: After a mean follow-up of
      38 months, the rate of progression of renal failure was 0.004 (0.039)
      dL/mg/month. Progression of renal disease showed no correlation with baseline
      ambulatory systolic or diastolic blood pressures, and did not differ between
      dipper and non-dipper patients. Twenty-four-hour (r = 0.40, p = 0.05) and day
      time (r = 0.534, p = 0.007) heart rates showed a relationship with the
      progression of renal failure. Proteinuria displayed a correlation with night-time
      heart rate (r = 0.405, p = 0.05) but not with the progression of renal failure.
      CONCLUSIONS: Baseline ambulatory heart rate, especially day-time heart rate, is
      associated with the decline of renal function in non-diabetic patients with
      chronic renal failure, suggesting that heart rate is a risk factor (or marker)
      for renal disease progression. Prospective controlled studies with a larger
      sample of patients are needed to confirm these findings and to investigate the
      possible mechanisms involved in this association.

PMID- 12236984
TI  - [An opportunity for Bayes].

PMID- 12236985
TI  - [Surrogate end points as a clinical and public health problem. The cerivastatin
      case].

PMID- 12236986
TI  - [Diabetic dyslipidemia: assessment and treatment].

PMID- 12236987
TI  - [Biomedical research tools: Bayesian perspective (I)].

PMID- 12236988
TI  - [Biomedical research tools: Bayesian perspective (II)].

PMID- 12236989
TI  - [Tratamiento del infarto agudo de miocardio con los nuevos farmacos
      tromboliticos].

PMID- 12236990
TI  - [Consumo de tabaco en los varones adolescentes].

PMID- 12236991
TI  - [Enterococcus faecium cholangitis resistant to vancomycin and quinupristin
      dalfopristin].

PMID- 12236992
TI  - [Primary pyomiositis by Rhodococcus spp. in an immunocompetent patient].

PMID- 12236993
TI  - [Borrelia burgdorferi meningoradiculopathy].

PMID- 12236994
TI  - [Thrombotic thrombocytopenic purpura occurringin association with acute
      pancreatittis].

PMID- 12236995
TI  - [Development of vaccinations against meningococcus: a long, winding, and still
      unfinished road].

PMID- 12236996
TI  - [Influence of adjuvants on the ability of anti-Tbp antibodies to block
      transferrin binding, iron uptake and growth of Neisseria meningitis].
AB  - OBJECTIVE: To evaluate the effect of five adjuvants on the ability of specific
      anti-TbpA/B to block iron uptake in Neisseria meningitidis. MATERIALS AND
      METHODS: Transferrin binding complexes (TbpA/B) purified from a TbpB isotype II
      Neisseria meningitidis strain were used to obtain sera with five different
      adjuvant formulations in mice in order to test the effect of the adjuvant on the
      ability of specific anti-TbpA/B antibodies to block transferrin binding, iron
      uptake and growth by meningococci. RESULTS: Levels of anti-TbpA/B antibodies were
      relatively low (1:125 in most cases), the highest being obtained with the RAS
      adjuvant (1:3125). Despite the relatively low responses, all sera were able to
      significantly inhibit transferrin binding, iron uptake and growth in the
      homologous strain. Nevertheless, the effect on a strain with a TbpB isotype
      different from that of the immunizing strain was almost nil, a result in keeping
      with the described division of the meningococci into at least two TbpB groups
      (isotypes I and II). CONCLUSIONS: In contrast to previous results for another
      important meningococcal protein, FbpA, the use of various adjuvants in the
      immunization of mice with TbpA/B complexes did not produce differences in the
      immune responses elicited, except in relation to antibody titers.

PMID- 12236997
TI  - [Epidemiology of Staphylococcus aureus nosocomial infections in a high-risk
      neonatal unit].
AB  - Nosocomial infections are a significant cause of morbidity and mortality
      throughout the world. In developing countries it is difficult to carry out
      effective surveillance and control programs for this type of infection because of
      the cost in both human and material resources. These considerations prompted us
      to perform a prospective study to determine the epidemiologic and microbiologic
      characteristics of nosocomial infections due to Staphylococcus aureus in the High
      risk Neonatal Unit (HRNU) of the Instituto Autonomo Hospital Universitario de Los
      Andes (IAHULA), during the period of November 1997 to October 1998. Among a total
      of 120 microorganisms, 24 (20%) strains of Staphylococcus aureus were isolated;
      47% were recovered from blood and 33% from conjunctive samples. Among the cases
      of conjunctivitis, S. aureus was the only pathogen isolated in 42%. Twenty of the
      24 Staphylococcus aureus strains (83%) were methicillin-resistant (MRSA).
      According to their resistance profiles, we established 12 groups of strains from
      neonates with nosocomial infections and 1 group of strains from the two carriers
      among the healthcare personnel detected by microbiological screening. The MeRGmR
      pattern was the most frequent. Plasmid analysis disclosed two profiles, each
      having a plasmid molecular weight over 23.130 bp. The MRSA strains isolated from
      the neonates and those isolated from the carriers showed the same plasmid
      profile. This suggests that the healthcare personnel may have acted as reservoirs
      of the MRSA strains found in neonates with nosocomial infection.

PMID- 12236998
TI  - [Enhanced quality in a hospital microbiology laboratory: from automation to
      clinical advice].
AB  - BACKGROUND: Quality policies focussed on the patient and applied to a hospital
      microbiology laboratory have led us to investigate clinicians' needs when
      requesting test results. The aim of this study was to analyze these requirements
      and to implement a plan to improve attention to the clinicians, considered as
      direct customers, particularly in the process of providing results. METHODS:
      Phase 1: To determine clinicians' needs, we studied the calls made to the
      Bacteriology Unit. Over a period of two weeks the information requested, the
      reasons for the call and the hospital Service calling were recorded. A
      descriptive analysis of this information was performed and the most frequent
      reasons for calling were identified. Phase 2: A quality improvement plan was
      designed to improve laboratory reporting of bacteriologic results. One month
      after its implementation, the results of this quality effort were assessed by
      analysis of calls to the Unit and use of a questionnaire to determine clinicians'
      satisfaction. RESULTS: Phase 1: among the total calls made, 43.8% asked for
      information on specimens being processed, 17.7% for information on specimens
      processed in other units, 16.1% demanded test results that had not been received
      within the expected time, and 22.4% were for other reasons. The hospital
      departments requesting information included 31% Infectious Diseases, 16% Internal
      Medicine, 13% Intensive Care Unit (ICU), and 40% others. Phase 2: within the
      quality plan, a microbiologist attended clinical sessions in the above mentioned
      departments in order to provide information on the specimens being processed, to
      discuss alternative diagnostic tests, and to comment on treatment prescribed to
      the patients. EVALUATION: Microbiologists attended two sessions per week during
      one month in the IM and ID Departments and ICU, and his/her participation was
      evaluated through analysis of calls and a satisfaction questionnaire. CONCLUSION:
      Automation of many laboratory tasks has allowed a reorientation of the activity
      of laboratory professionals toward satisfying the needs of the medical staff and
      improvements in the reporting process. The direct participation of laboratory
      professionals in discussions on patient care resulted in an enhancement of the
      overall quality of the health care provided to the patient.

PMID- 12236999
TI  - [Preliminary evaluation of the prevalence of tuberculosis infection in an
      occupational risk group].
AB  - BACKGROUND: The aim of this study was to gain knowledge on the prevalence of
      tuberculosis infection in occupational groups whose professional activity could
      implicate a high risk of contact with persons infected with Mycobacterium
      tuberculosis. Additionally, we sought to identify risk factors in order to
      establish effective measures for control and prevention. With this aim we carried
      out a pilot study among members of our police force. MATERIAL AND METHODS:
      Reactivity against tuberculin was tested in 150 individuals belonging to the
      Spanish National Police Force and an epidemiological survey was conducted to
      identify risk factors. RESULTS: The prevalence of tuberculin reactivity was
      10.7%. No correlation was found between positive testing and sex or years of
      service, but there was a correlation with respect to age. CONCLUSIONS: The
      prevalence data and the experience obtained in this pilot study enable us to
      continue working toward the establishment of an effective control program.

PMID- 12237000
TI  - [Antimicrobial prophylaxis in surgery].
AB  - Antimicrobial prophylaxis in surgery refers to a very brief course of an
      antimicrobial agent initiated just before the start of the procedure. The
      efficacy of antimicrobials to prevent postoperative infection at the site of
      surgery (incisional superficial, incisional deep, or organ/space infection) has
      been demonstrated for many surgical procedures. Nevertheless, the majority of
      studies centering on the quality of preoperative prophylaxis have found that a
      high percentage of the antimicrobials used are inappropriate for this purpose.
      This work discusses the scientific basis for antimicrobial prophylaxis, provides
      general recommendations for its correct use and specific recommendations for
      various types of surgery. The guidelines for surgical antimicrobial prophylaxis
      are based on results from well-designed studies, whenever possible. These
      guidelines are focussed on reducing the incidence of infection at the surgical
      site while minimizing the contribution of preoperative administration of
      antimicrobials to the development of bacterial resistance.

PMID- 12237001
TI  - [Structure and function of integrons].
AB  - Integrons are genetic elements known for their role in the acquisition and
      expression of genes conferring antibiotic resistance. Integrons have an integrase
      gene (intI), an attachment site (attI), into which individual resistance genes
      are inserted and a promotor sequence (Pant), allowing expression of resistance
      genes (cassette-associated genes), which do not have promotors. Integrase
      recognizes 59-be, a specific sequence in certain resistance genes, which is
      captured by recombination at the attI attachment site. The fragment intI - attI
      is highly conserved in all integrons and is called 59 -CS. Integrons have been
      classified according to the sequence of their integrase and the ones most
      frequently detected in isolated clinical strains belong to Class I. Class I
      integrons contain the 59 -CS region followed by gene cassettes in a variable
      region and finally, a conserved region known as 39 -CS containing two genes, the
      quaternary ammonium resistance gene (qacEDI) and the sulphonamide resistance gene
      (sul1); both genes are fixed in this structure. Accordingly, the structure of a
      Class 1 integron would be IntI - attI [R11 R21.] - qacED1 - sul1. Integrons are
      probably not mobile, but they are often found in transposons within conjunctive
      plasmids, which assures their mobility, as can be seen by their wide diffusion
      among bacteria.

PMID- 12237002
TI  - [Factors affecting the virulence and pathogenicity of avian and human viral
      strains (influenza virus type A)].
AB  - Most studies performed in avian viral strains seem to indicate that virulence is
      a polygenic phenomenon. However, hemagglutinin and neuraminidase and the genes
      codifying these substances (genes 4 and 6) play an essential role in viral
      pathogenesis. Avian strains can be classified as avirulent or virulent according
      to the ability of hemagglutinin to be activated by endoproteases of the
      respiratory tract only or by proteases from other tissues. This ability is based
      on the progressive development of mutations that lead to the substitution of the
      normal amino acids at the point of hemagglutinin hydrolysis by the other basic
      amino acids that determine the amplification of the spectrum of hydrolysis and
      activation. Neuraminidase participates in the acquisition of virulence through
      its capacity to bind to plasminogen and by increasing the concentration of
      activating proteases. Adaptation to the host, through recognition of the cell
      receptor, is another factor determining the virulence and interspecies
      transmission of avian strains. From an epidemiological point of view, viral
      strains should be subtyped and the activating capacity of hemagglutinin should be
      determined to identify their degree of virulence.

PMID- 12237003
TI  - [Interpretative reading of the antibiogram in gram-positive cocci].
AB  - Resistance to methicillin in Staphylococcus is related to expression of the gene
      mecA, and implies resistance to all beta-lactams. Breakpoints for interpretation
      of this mechanism differ in S. aureus and in coagulase-negative species. In
      relation to macrolides-lincosamides-streptograminsB, the most frequent mechanism
      among resistant strains is expression of methylases (erm genes). Topoisomerase
      changes caused by point mutations and expression of the efflux pump NorA
      determine resistance to quinolones, but there are great differences on the
      activity of different compounds, which makes interpretative reading difficult.
      Strains of S. aureus with intermediate susceptibility to glycopeptides (GISA
      strains) have been recently described. In Spain, there is a high percentage of S.
      pneumoniae strains intermediate or resistant to penicillin, and a low percentage
      of strains intermediate or resistant to third generation cephalosporins, because
      of mutations in genes encoding penicillin-binding proteins. The most frequent
      phenotype of resistance to macrolides in this species is caused by methylase
      production. Resistance to quinolones is still uncommon, and is related to the
      mechanisms previously indicated for Staphylococcus, but clinical interpretation
      of the antibiograma for this organism is even more complex. No strains of S.
      pyogenes resistant to penicillin have yet been described. In Spain the most
      common phenotype of resistance to macrolides in S. pyogenes is determined by
      efflux pumps (mef genes), affecting 14- and 15-membered macrolides. E. faecalis
      is usually susceptible to ampicillin, in contrast to E. faecium. Enterococci show
      intrinsic resistance to aminoglycosides, but still remain susceptible to the
      combination of these antimicrobials and cell-wall active agents. Strains
      expressing different aminoglycoside-modifying enzymes became resistant to the
      combination. Glycopeptide-resistant strains of enterococci are uncommon in our
      country, but several genotypes, of which vanA is the most relevant from a
      clinical point of view, have been described in other regions.

PMID- 12237004
TI  - [Acute abdominal pain and ascites in a young woman].

PMID- 12237005
TI  - [English in Enfermedades Infecciosas y Microbiologia Clinica].

PMID- 12237006
TI  - [Prevalence of Chlamydia trachomatis in an Asturian population at risk].

PMID- 12237007
TI  - [Acute cholecystitis due to Kluyvera ascorbata].

PMID- 12237008
TI  - [Acute arthritis-dermatitis syndrome due to Neisseria meningitis].

PMID- 12237009
TI  - [Surgery for lung metastasis].

PMID- 12237010
TI  - [Hookwire localization of pulmonary nodules for video-thorascopic surgical
      resection].
AB  - OBJECTIVES: To assess the usefulness of a technique for inserting hookwires
      guided by computed tomography to locate and resect pulmonary nodules by video
      assisted thoracoscopy. To describe the procedure and its complications. PATIENTS
      AND METHODS: Nine pulmonary nodules were located in nine patients. All were </= 2
      cm in diameter, radiologically undefined and of unknown origin. Four patients had
      a history of cancer. The nodules were located using the needle/hookwire system
      (Kopans), guided by computed tomography and were resected by video-assisted
      thoracic surgery. RESULTS: The hookwire was placed correctly in 8 patients and
      incorrectly in 1. Thoracotomy was necessary for 1 patient. The histologic
      diagnosis was benign for all 9 nodules; 5 were hamartomas, 2 were necrotic or
      fibrotic nodules, 1 was a granuloma and 1 was an anthracotic node. Hospital stay
      ranged from 1 to 8 days (mean 3.3 days). CONCLUSION: The location of pulmonary
      nodes by hookwire and needle for later resection by video-assisted thoracoscopic
      surgery is a simple, safe way to facilitate removal in some cases, for diagnosis
      and treatment.

PMID- 12237011
TI  - [Multicenter experience of video-assisted thoracic surgery to treat mediastinal
      cysts and tumors].
AB  - OBJECTIVE: In spite of improvements in imaging techniques, surgical procedures
      are often needed to diagnose and definitively treat mediastinal masses. The range
      of application of video-assisted thoracic surgery (VATS) in this context is still
      poorly defined. The present study describes and analyzes the experience of the
      Cooperative Group for Video-assisted Thoracoscopic Surgery of the Spanish Society
      of Pneumology and Thoracic Surgery (GCCVT-SEPAR), with the aim of determining the
      usefulness of the technique for treating mediastinal cysts and tumors. METHOD:
      For 2 years we gathered information prospectively on 1,573 consecutive VATS
      procedures in 17 hospitals. The data from 64 procedures performed for diagnosis
      and treatment of mediastinal cysts and tumors are analyzed. RESULTS: A definitive
      diagnosis was reached in all cases. Nineteen were malignant tumors and 45 were
      benign lesions. Twenty-five complete resections (39%) were performed: 6
      pleuropericardial cysts, 4 bronchogenic cysts, 8 neurogenic tumors and other
      benign lesions. Radiologically poorly defined masses and those located in the
      anterior and median parts of the mediastinum were most often the object of
      diagnostic procedures, whereas cysts and well-defined solid lesions on the
      posterior mediastinum were usually the object of therapeutic interventions.
      Eleven percent of the cases required conversion to thoracotomy, mainly due to
      pleural adhesions. Four complications (6.3%) were recorded and no deaths
      occurred. The median hospital stay after surgery was 2.5 days; 7.8% of the
      procedures were performed on outpatients. CONCLUSIONS: VATS is performed on many
      mediastinal lesions in Spain. Cysts and benign tumors are selected for resection.
      Poorly defined and malignant lesions were diagnosed by biopsy. The experience
      reported demonstrates the efficacy and safety of this technique for selected
      cases.

PMID- 12237012
TI  - [Usefulness of video-assisted thoracoscopy for the diagnosis of solitary
      pulmonary nodules].
AB  - OBJECTIVES: Various approaches are used for the diagnosis and treatment of
      solitary pulmonary nodules (SPN) of unknown origin. New imaging techniques and
      nuclear medicine have provided more information about SPN, but surgical removal
      is still the most sensitive and specific way to obtain a correct analysis of the
      lesion. With video-assisted thoracic surgery (VATS), a histological diagnosis can
      be obtained without resorting to thoracotomy. In the present study we describe
      our experience with the diagnosis and treatment of SPN using VATS. MATERIAL AND
      METHODS: From July 1992 through April 2001, 182 patients were operated on for SPN
      in our department. DESIGN: Retrospective study. Mean age: 59.2 years (12-78).
      Sex: 39 women and 143 men. Localization: Visual or instrumental exploration in
      102 patients, with palpation in 52 cases and using a hookwire guided by
      preoperative computed tomography in 25 (with failure in 4 of those cases). Tissue
      was biopsied during surgery and when the lesion was malignant, oncological
      excision was performed during the same operation. RESULTS: A firm diagnosis was
      obtained by VATS for 178 patients (98.3%). For three other patients the surgeon
      had to take a needle biopsy (Tru-cut) during surgery, and in one case conversion
      to open surgery was necessary. Histopathology: hamartoma: 11; fibrous nodule: 10;
      bronchiolitis obliterans: 1; pneumoconiosis: 1; mesenchymal tumor: 3;
      inflammatory pseudotumor: 14; mucormycosis: 1; tuberculoma:17; lymphoma: 1;
      carcinoid tumor: 6; metastasis: 22; bronchogenic carcinoma: 95. Mortality was
      0.55%, with 1 patient dying from massive pulmonary thromboembolism. Morbidity was
      5%, from 9 minor complications. CONCLUSIONS: VATS is an effective approach, with
      low morbidity and mortality. We consider it to be the technique of choice for the
      diagnosis of all SPN and for the treatment of some, such as benign nodules and
      solitary metastases.

PMID- 12237013
TI  - [Our experience in the treatment of hyperhidrosis of the upper limbs by video
      assisted thoracoscopy: an analysis of our first 100 procedures].
AB  - Sympathectomy of the thoracic chain is an effective surgical procedure for
      treating axillary and palmar hyperhidrosis. The procedure has been performed with
      minimal invasion and good results in recent years through the use of
      videothoracoscopic surgery. This paper describes the technique and our experience
      with a series of 50 patients between 16 and 48 years old. The earliest approach
      was unilateral in successive operations. The procedure was later performed
      bilaterally, at first with the patients in sequential lateral decubitus positions
      and later in semi-seated position. Complications were 1 case of incomplete Claude
      Bernard-Horner syndrome that resolved spontaneously two months after surgery; 1
      failure when sympathectomy was performed without location of the chain, obliging
      rapid re-operation; laminar pneumothorax in 12% of the series; compensatory
      hyperhidrosis in 26%; 10% with chest pain due to intercostal involvement,
      resolving with time; and slight bleeding in 8%. Outcome was excellent, with
      complete disappearance of axillary and palmar perspiration. Patient satisfaction
      was 9.2/10 one year after surgery. Mean hospital stay was less than 36 h.

PMID- 12237015
TI  - [The need to measure objectively in medicine and its difficulties].

PMID- 12237014
TI  - [Use of the Internet in a multicenter study of chronic obstructive pulmonary
      disease in primary care. Pilot phase of the EFEMAP study].
AB  - OBJECTIVE: To determine the reliability of clinical data collection and
      transmission by Internet in a multicenter primary care study. PATIENTS AND
      METHODS: Multicenter, observational study of a population of patients with
      exacerbated chronic obstructive pulmonary disease (COPD). All data were gathered
      in a specifically designed digital program on a palm-held pocket computer.
      Information was transmitted on-line by modem to a central database. RESULTS:
      Thirty-nine researchers participated in this pilot phase. Over three months 324
      patients were treated. Thirty-seven telephone consultations were generated, most
      (54%) in reference to how the digitized questionnaire worked. Questions were
      solved in a mean 5.44 minutes. No important technical problems occurred and no
      information was lost. CONCLUSIONS: The use of the Internet to transfer data for
      multicentric studies in primary care is possible. This system should be more
      widely used in the future, as it allows faster data collection and eliminates the
      need to input data at the end of the study.

PMID- 12237016
TI  - [Response to glucocorticoid treatment in asthma. The role of alpha and beta
      isoforms of the glucocorticoid receptor].

PMID- 12237017
TI  - [SEPAR guidelines. Guidelines for tuberculosis prevention].

PMID- 12237018
TI  - [Lung function in the course of amyotrophic lateral sclerosis].
AB  - We report a case of a 26 year old man who was diagnosticated of ALS. This case is
      a graphic example of the pulmonary function evolution through the flow-volume
      loop. In the first study the espirometric values were in the normal range. The
      Static pulmonary pressures were weackle decreased. This was the only sign of
      respiratory muscle impairement. Its important to study close enough the pulmonary
      function through the flow/volume loop, maximal respiratory pressures and maximal
      voluntary Ventilation in order to know the empairment rate, and also to detect
      intercurrent procedures as bulbar involvement, that can affect the prognosis of
      the disease.

PMID- 12237019
TI  - [Traumatic diaphragm injuries: a review of 8 cases].
AB  - Traumatic rupture of the diaphragm is a rare event that is usually found in
      polytrauma cases or after violent attacks. Patients are usually males between 20
      and 50 years old, and car accidents are the main causes. Diagnosis can be
      difficult and injuries may go unnoticed, leading to serious delayed
      complications. We present 8 cases from 1991 through 2000. All patients came to
      the emergency department of our hospital with a diagnosis of traumatic rupture of
      the diaphragm. We analyze the reasons for admission, signs and symptoms,
      diagnostic approach, associated lesions, treatment and course, comparing our
      experience with reports in the literature.

PMID- 12237020
TI  - [Granular cell tumors. Diagnostic approach during an aggressive clinical course].

PMID- 12237021
TI  - [Sclerosing pulmonary hemangioma: a tumor that is easy to confuse with
      bronchogenic carcinoma].

PMID- 12237022
TI  - [Clinical Practice Guidelines. A step forward].

PMID- 12237023
TI  - [Smoking cessation in primary and specialized care: a real opportunity and a
      public health necessity].
AB  - AIM: To determine whether primary care provides a suitable framework for
      integrated treatment aimed at smoking cessation with systematic minimal
      intervention or pharmacological treatment with nicotine replacement therapy
      (NRT). To compare the results with those obtained in a specialized pneumology
      unit. DESIGN: Prospective, quasi-experimental study. SETTING: Primary and
      specialized care services. PARTICIPANTS: 357 smokers who were followed at a
      health center (166) or a specialized clinic (191) during a 6-month period.
      INTERVENTIONS: Two types of intervention were used depending on the patients'
      degree of nicotine dependence: systematic minimal intervention for those with low
      dependence or who were still in the contemplation or precontemplation phase, and
      NRT for those with high dependence, in the preparation phase. MAIN OUTCOME
      MEASURES: Twelve months after the start of the study, abstinence among
      participants who received systematic minimal intervention was 36.5% in primary
      care patients and 41.8% in specialized care patients (P>.05). Among participants
      who received NRT abstinence was 37.1% in the former group and 35.5% in the latter
      (P>.05). The percentage of patients lost to follow-up was 8.6% in specialized
      care and 6.3% in primary care. CONCLUSIONS: The results lead us to recommend
      smoking cessation treatment integrated in the primary care setting, either with
      systematic minimal intervention or NRT.

PMID- 12237025
TI  - [Prevalence study of cardiovascular risk factors in a health area].
AB  - OBJECTIVE: To calculate the prevalence of cardiovascular risk factors:
      hypertension, hypercholesterolaemia, diabetes mellitus (DM), obesity and tobacco
      dependency, in Health Area 20 of the Community of Valencia. DESIGN: Cross
      sectional, descriptive, observational study. SETTING: Population study carried
      out in Health Area 20 of the Community of Valencia (Vega Baja del rio Segura
      county). PATIENTS: >=20 years-old people, living in this area. Multi-stage
      randomised sample proportional to the definition of sample quotas according to
      the kind of residence (urban, peri-urban or rural), age groups and sex.
      Calculated sample size of 2550 people. Pregnant women and people diagnosed with
      incapacitating psychiatric or physical illnesses (134) were excluded. The rest
      (2416) were included. MEASUREMENTS: A questionnaire was filled out in a face-to
      face interview and a basic physical examination was made. A blood sample was
      taken. The following variables were recorded: personal details, social and
      economic details, previous illnesses (cardiovascular, hypertension,
      hypercholesterolaemia, DM), tobacco habit, Body Mass Index, blood pressure,
      haemogram and standard biochemical test. The most recently agreed and recommended
      diagnostic criteria were used for each factor. RESULTS: 1886 people of the 2416
      eligible took part (78.06%). Prevalence was as follows: hypertension, 30.3+/-2.1%
      (women, 34.1+/-2.9%; men, 25.8+/-2.9%); hypercholesterolaemia, 22.6+/-1.9%;
      diabetes, 8.4+/-1.2%; tobacco dependency, 33.6+/-2.1% (women, 25.4+/-2.7%; men,
      42.2+/-3.3%; 20-39 years old age-group, 56.9+/-3.8%), and obesity, 31.6+/-2.1%
      (women, 34.6+/-2.9%; men, 28.1+/-3%; age group >=60 years old, 46.7+/-3.9%).
      Detection data were shown. CONCLUSIONS: High presence of hypertension,
      hypercholesterolaemia, diabetes and obesity, greater than the country-wide level.
      Tobacco dependency was less common, though very high in young people. Known
      hypertension and obesity are more common in women than men.

PMID- 12237026
TI  - [Epidemiological study of risk behaviour in adolescents at school in two
      populations, semi-rural and urban].
AB  - OBJECTIVE: Describe the risk behavior relationships existing in school
      adolescents between themselves and with the place of residence. DESIGN: Cross
      sectional descriptive study. PARTICIPANTS: School students from Cabra (semi
      rural, 1319 students) and from one high school in Las Palmas de Gran Canaria
      (urban: 1,751 students). SAMPLE POPULATION: n=738 (368/370). Sampling unit
      classroom. MEASUREMENTS AND MAIN RESULTS. Anonymous, self-filled questionnaire,
      with several subjects: demographic data, traffic-related risk conducts, alcohol
      consumption, tobacco, other drugs, sexuality, physical exercise and dietetic
      habits. SELECTION CRITERIA: attendance at class on the day of the questionnaire
      and age 15-21. The relationship between variables was studied by logistical
      regression and multiple correspondence analysis (MCA); odds ratio (OR: logistical
      regression) with 95% confidence intervals (CI) were calculated. Median age: Cabra
      17.6 (CI, 17.5-17.8), Las Palmas 16.4 (CI, 16.2-16.5). Those living in Las Palmas
      have a higher risk of heavy drinking on weekends (OR, 3.2; CI, 1.9-5.1), of being
      offered drugs (OR, 4.5; CI, 3.1-6.5) and of consuming them (OR, 4.1; CI, 2.1
      8.3), as well as of having sexual intercourse (OR, 2.5; CI, 1.6-3.8). In the MCA
      tobacco, alcohol and other drug use, having sexual intercourse and not doing
      regular physical exercise were closely-located within themselves. CONCLUSIONS:
      Risk behaviours are interrelated and influenced by the habitat, and start to
      appear at the beginning of the adolescence.

PMID- 12237027
TI  - [Tobacco consumption among adolescents. Value of the intervention of health
      service staff].
AB  - OBJECTIVES: To describe the characteristics of tobacco consumption among
      adolescents seen at a health centre, find their opinions of the factors that
      affect consumption, and analyse the quality of the intervention of the health
      staff. DESIGN: Descriptive, cross-sectional study of adolescents attending the
      health centre. SETTING: Primary care (PC). PATIENTS: All the young people between
      10 and 20 who attended family medicine, paediatric or nursing clinics, whether on
      demand or with appointments, on Tuesdays and Wednesdays between December 2000 and
      February 2001. MAIN RESULTS: 23.1% of all the girls smoked (95% CI, 14.9-33.1)
      versus 15.3% of boys (95% CI, 8.4-24.7). Among non-smokers the main reason for
      not smoking was health (94.4%). 50% of smokers had tried to give up, of whom
      70.5% tried for health-related reasons. 49.4% (95% CI, 41.8-57.1) of those
      included in the study had been asked at the health centre on some occasion
      whether they smoked (10.1% of these [95% CI, 4.2-19.8] were aged 10-13; 73.4%
      [95% CI, 60.9-83.7] 14-17; and 76.7% [CI 95%: 61.4-88.2] 18-20); and 50.6% had
      never been asked. Of those who were asked and did smoke, 75% (95% CI, 55.1-89.3)
      were advised to give up and 4.7% of these (95% CI, 0.1-23.8) were offered help to
      do so. 28.81% of those who did not smoke (95% CI, 17.8-42.1) were encouraged to
      continue not to smoke. CONCLUSIONS: Both smokers and non-smokers are highly aware
      of the repercussions of tobacco on health. Tobacco dependency in young people was
      not tackled well enough at health centre clinics, especially by paediatricians.

PMID- 12237028
TI  - [Towards the definition of a set of a basic minimum data in primary care].

PMID- 12237029
TI  - [System of primary care accreditation (SaAP) (I): challenges of ongoing
      training].

PMID- 12237030
TI  - [Immunisation: leaps into the future. The flu virus and syncytial respiratory
      virus: strategies for active immunisation].

PMID- 12237032
TI  - [Profile of patients under treatment with heparin of low molecular weight].

PMID- 12237033
TI  - [Low sweat secretion due to topiramate].

PMID- 12237034
TI  - [Robinin intoxication].

PMID- 12237035
TI  - [Experimental heroin maintenance programmes: the distance between what might be
      done and what is really done].

PMID- 12237036
TI  - [Quality of the biomedical information existing on the Internet: Web Medica
      Acreditada, a Spanish initiative].

PMID- 12237039
TI  - Hybrid parametric-physiological glottal modelling with application to voice
      quality assessment.
AB  - A glottal model based on physical constraints is proposed. The model describes
      the vocal fold as a simple oscillator, i.e. a damped mass-spring system. The
      oscillator is coupled with a nonlinear block, accounting for fold interaction
      with the airflow. The nonlinear block is modelled as a regressor-based functional
      with weights to be identified, and a pitch-synchronous identification procedure
      is outlined. The model is used to analyse voiced sounds from normal and from
      pathological voices, and the application of the proposed analysis procedure to
      voice quality assessment is discussed.

PMID- 12237041
TI  - A method for measurement of the vocal tract impedance at the mouth.
AB  - In this contribution a method is presented for the measurement of vocal tract
      resonances. The technique uses a non-invasive acoustic excitation of the vocal
      tract and a fast and robust detection. The method is an alternative to the linear
      predictive coding (LPC) analysis for patients with voice and speech disorders.
      Sweep signals are emitted and recorded simultaneously from the small end of a
      tube placed in front of the mouth opening. The use of a pressure sensor and a
      velocity sensor provides a direct measurement of the vocal tract impedance at the
      mouth (VTMI). For selected sustained German vowels, and some consonants, a
      comparison of results from LPC analysis and VTMI measurements is given. The
      results indicate a good agreement in the frequency range from 500 to 5,000 Hz.
      The feasibility of the VTMI method for diagnostic and therapeutic applications is
      subject to current research.

PMID- 12237040
TI  - Stimulated production of vowel-like LX-waveforms and spectral damping in the
      absence of phonation.
AB  - Electrical impedance 'LX' waveforms measured across the neck at the thyroid level
      during phonation are known to be correlated with vocal fold movement. Changes in
      vocal fold contact are thought to be the cause of this phenomenon though emerging
      applications in radiotherapy indicate that changes in the configuration of both
      fold and neck tissues are correlated with LX waveform shape. In this paper it is
      shown that a two-stage tissue damping model with controlled bandpass and passive
      low pass components is consistent with evidence from gradually degraded,
      controlled phonation. In particular it is shown that an externally applied
      stimulus to the vertebral processes of the neck can produce similar impedance
      waveforms in the absence of phonation and hence no controlled fold contact. It is
      postulated that this is initial evidence suggesting that both pressure waves and
      vocal fold contact components contribute to the production of the classical 'LX'
      waveform.

PMID- 12237042
TI  - A study of the central control of vocalization using the squirrel monkey.
AB  - In the squirrel monkey (Saimiri sciureus), the electrical activity of single
      neurones was compared in the periaqueductal grey of the midbrain and the
      reticular formation of the medulla oblongata during vocalization, using a
      recently developed telemetric technique. The results show that both structures
      contain neurones with vocalization-correlated activity. There are characteristic
      differences between the two structures, however. Neurones showing changes in
      discharge rate with changes in fundamental frequency were only found in the
      reticular formation, whereas neurones firing immediately before vocalization, but
      not during vocalization, were almost exclusively found in the periaqueductal
      grey. It is concluded that the reticular formation is involved in vocal motor
      coordination, while the periaqueductal grey mainly serves gating functions.

PMID- 12237043
TI  - Quantitative values for perceptual notion of speech speed.
AB  - Although it is widely used in everyday activities and in several professions such
      as locution, shorthand and stenography among others, the magnitude speed of
      speech does not have a precise meaning in everyday use. Such precision is
      fundamental in the context of the study of the typical behaviour of a large set
      of language allophones as the basic components for robust speech synthesis. No
      information was found for Spanish and less for the variant spoken in Uruguay and
      the center and south of Argentina, usually called Riverplatean Spanish. This
      article presents a quantitative characterization of the intuitive notions of
      fast, slow and normal speech speed. The article reports research with strong
      experimental foundation since its conclusions were obtained from 120 texts
      uttered by different speakers at different speeds in a context free of any sort
      of conditioning. More than a half of the texts were collected from public sources
      and from people who never knew they were being recorded for this purpose.

PMID- 12237044
TI  - Experimental comparison between a Staffieri and a New Prototype tracheo
      oesophageal valve.
AB  - A tracheo-oesophageal valve is used for the rehabilitation of patients who have
      lost vocal function due to a total laryngectomy. The valve is positioned in a
      surgically created fistula between the airway and the upper oesophagus at the
      level of the post-laryngectomy stoma. It permits passage of air from the trachea
      to the pharynx to permit speech, while it blocks the flow of secretions and food
      materials from the digestive tract to the airway. In this paper, experimental
      results obtained with a Staffieri and a New Prototype tracheo-oesophageal valve
      are presented. The valves have been tested experimentally under different
      conditions of airflow through the valve and tracheal-side pressure; the airflow
      resistance has been calculated to compare the performance of the valves. The
      valves have also been experimentally tested under different conditions of fluid
      flow through the valve and oesophageal-side pressure. The airflow resistance of
      the Staffieri and the New Prototype valves has been compared for different
      angular extents, alpha, of the razor-thin slit through which the airflow passes.
      For each type of valve the parameter alpha has a significant influence on flow
      characteristics, while the shape of the dome becomes important only for the
      larger angular extents considered.Regarding the reverse flow, it is pointed out
      that for both of the valve types at different oesophageal pressures and for
      smaller angular extents of the razor-thin slit, the reverse fluid flow through
      the valves is smaller than the allowable reverse flow, that can be tolerated by
      patients without creating problems. In general, for high values of the angular
      extent of the razor-thin slit the Staffieri valve offers the least flow
      resistance, but, unlike the New Prototype, the direct flow under these conditions
      in unacceptably large.

PMID- 12237045
TI  - The real and the non-real in speech measurements.
AB  - The measurement of parameters from the output acoustic pressure waveform during
      speech has been a common activity in speech science laboratories for a number of
      decades. The widespread availability of personal computers with more than
      adequate processing capability to carry out speech analysis means that speech
      analysis is now commonly available and many more users have access to it. Indeed,
      there are some highly comprehensive speech analysis software packages available
      for PC computers as freeware. However, the results gained from speech analysis
      are not always a function only of the speech input itself, as there are some
      often surprising pitfalls to be aware of, due to the nature of the chosen
      measurement technique itself. This paper explores commonly applied speech
      analysis techniques and focuses particularly on some potential pitfalls and their
      consequences.

PMID- 12237046
TI  - Developmental aspects of infant's cry melody and formants.
AB  - This paper deals with the analysis of cry melodies (time variations of the
      fundamental frequency) as well as vocal tract resonance frequencies (formants)
      from infant cry signals. The increase of complexity of cry melodies is a good
      indicator for neuro-muscular maturation as well as for the evaluation of pre
      speech development. The variation of formant frequencies allows an estimation of
      articulatory activity during pre-speech vocalization. Subjects are three pairs of
      healthy identical twins (monocygozity determined by DNA-fingerprint). Spontaneous
      cries of these six children were recorded at different ages: 8th-9th week, 15th
      17th week and 23rd-24th week. Analysis of 136 cry melodies and intensity contours
      was made using KAY-CSL 4300/MDVP. For formant estimation a spectral parametric
      technique was applied, which was based on autoregressive models (Digital spectral
      analysis with applications, 1987) whose order is adaptively estimated on
      subsequent signal frames by means of a new method (Med. Eng. Phys. 20 (1998) 432;
      Utras. Med. Biol. 21 (1995) 793). Cry melodies exhibited an increasing complexity
      during the observation period. Beginning with the second observation period (15th
      17th week) an increasing coupling and tuning between melody and resonance
      frequencies was observed, which was interpreted as "intentional" articulatory
      activity. Possible applications are in cry diagnosis as well as in the evaluation
      of pre-speech development.

PMID- 12237047
TI  - Reconstruction of speech from whispers.
AB  - This paper investigates a method for the real-time reconstruction of normal
      speech from whispers. This system could be used by aphonic individuals as a voice
      prosthesis. It could also provide improved verbal communication when normal
      speech is not appropriate. The normal speech is synthesized using the mixed
      excitation linear prediction model. Differences between whispered and phonated
      speech are discussed and methods for estimating the parameters of this model from
      whispered speech for real-time synthesis are proposed. This includes smoothing
      the noisy linear prediction spectra, modifying the formants, and synthesizing of
      the excitation signal. Trade-offs between computational complexity, delay, and
      accuracy of different methods are discussed.

PMID- 12237048
TI  - Identifying a differential equation for lip motion.
AB  - A second order homogeneous differential equation is fitted to lip trajectories
      during speech at fast, normal, and slow speaking rates. The objective is to
      characterize lip motion in terms of biomechanical parameters such as stiffness,
      damping, and applied external forces. The results show that, at fast speaking
      rates, the lip behaves like a simple mass-spring oscillator moving at its natural
      frequency, and with low variability across repetitions. At slow speaking rates,
      on the other hand, the lip is under a stronger external control to conform to the
      required trajectory, which introduces a larger variability across repetitions.
      The case of normal rate falls between the fast and slow rate cases.

PMID- 12237049
TI  - Non-linear prediction for oesophageal voice analysis.
AB  - Herein, non-linear prediction methods are applied to oesophageal voice analysis.
      The research aims to investigate normal and pathological subjects, in order to
      improve knowledge of the oesophageal voice behaviour. Analysis is performed in
      the reconstructed phase space, using both non-linear prediction with local linear
      approximation and the S-Map method. Preliminary results seem to confirm that in
      normal subjects a non-linear stable deterministic behaviour takes place, while in
      pathological subjects the non-linear contribution reduces while the time series
      becomes unstable.

PMID- 12237050
TI  - Assessing the sound of cough towards vocality.
AB  - The presented research positively evaluates the vocality of the cough sound by
      estimating the global cough fundamental frequency or pitch. The fundamental
      frequency was determined by autocorrelation analysis on both the original time
      signal and the linear predicted time-signal. The experimental cough database was
      registered in the free acoustical field on respectively three pathological and
      nine healthy non-smoking human subjects and on two pathological and two healthy
      Belgian Landrace piglets. For both species differences between pitch values for
      cough-sounds originating from subjects suffering from a respiratory infection and
      healthy subjects are put forward. The retrieved pitch-difference between
      respectively healthy and infected subjects indicates the existence of
      acoustically different cough-classes in accordance with a different cause or
      physical condition of the respiratory system.

PMID- 12237051
TI  - Automated recognition of spontaneous versus voluntary cough.
AB  - Cough or cough epochs may be an important and persistent symptom in many
      respiratory diseases requiring both a continuous and objective observation. The
      research presented in this paper is aimed at assessing a blind data-based
      classification between 'spontaneous' and 'voluntary' human cough on individual
      sound samples. Cough sounds were registered in the free acoustic field on 3
      pathological and 9 healthy non-smoking subjects, all aged between 20 and 30. Each
      sound is represented by the normalized power spectral density (PSD). Different
      transformations of the cough PSD-vector are chosen as input features to the
      classification algorithm. An experimental error rate comparison between different
      neural and fuzzy classification networks is performed. All evaluated algorithms
      used the Euclidean metric. This resulted in a correct class-discrimination
      between 'spontaneous' and 'voluntary' cough for 96% of the cough database.

PMID- 12237052
TI  - Noise reduction for vocal pathologies.
AB  - A noise reduction scheme, particularly suited for the correction of vocal
      pathologies, is proposed. The filter makes use of concepts originated within the
      theory of dynamical systems and deterministic chaos. In particular, the idea of
      embedding scalar data in order to reconstruct a phase space is of fundamental
      importance here. Furthermore, the concept of an attractor as a result of
      dynamical constraints is exploited. In order to perform noise reduction one needs
      redundancy and the human voice provides it even within a phoneme, namely the
      smallest structural unit of speech. Due to several repetitions of a pattern
      called pitch inside a phoneme, separation between the pure voice signal and the
      noise is possible, provided the latter is uncorrelated with the former. With a
      proper parameter tuning, different kinds of noise can be removed. We describe the
      idea behind the noise reduction algorithm and present applications to vocal
      pathologies.

PMID- 12237053
TI  - Quantitative assessment of the use of continuous wavelet transform in the
      analysis of the fundamental frequency disturbance of the synthetic voice.
AB  - The aim of this work is to investigate quantitatively the capability of the
      Continuous Wavelet Transform (CWT) as a tool to estimate (calculate) Jitter and
      Shimmer, assessing the error between these indices calculated in each Wavelet
      decomposition and the ones for the original signal, for several dilatation
      levels. Two synthetic vowels /a/ were generated with the fundamental frequencies
      of 120 Hz for male and 220 Hz for female, by an autoregressive 22 coefficient all
      pole model, and Jitter and Shimmer were introduced to the signal using five
      different percentage variations. The signals were decomposed by CWT in eight
      levels of dilatation (1, 2, 4, 8, 16, 32, 64 and 128), using the Mexican Hat,
      Meyer and Morlet real bases. Jitter and Shimmer were calculated for the original
      signals and all eight levels of decompositions and then the errors between the
      indices in the decompositions and the original signals were calculated. It can be
      concluded that CWT can be used as a tool for pre-processing the signal to measure
      Shimmer preferentially, and Jitter, instead of using the original signal to do
      that. The Mexican Hat base provided the lowest errors for Shimmer analysis, where
      the best dilatation level was 8 (error below 0.1%). In addition, the errors
      associated with Shimmer index, in general, are lower than the ones associated
      with Jitter index.

PMID- 12237054
TI  - Pathological voice quality assessment using artificial neural networks.
AB  - This paper describes a prototype system for the objective assessment of voice
      quality in patients recovering from various stages of laryngeal cancer. A large
      database of male subjects steadily phonating the vowel /i/ was used in the study,
      and the quality of their voices was independently assessed by a speech and
      language therapist (SALT) according to their seven-point ranking of subjective
      voice quality. The system extracts salient short-term and long-term time-domain
      and frequency-domain parameters from impedance (EGG) signals and these are used
      to train and test an artificial neural network (ANN). Multi-layer perceptron
      (MLP) ANNs were investigated using various combinations of these parameters, and
      the best results were obtained using a combination of short-term and long-term
      parameters, for which an accuracy of 92% was achieved. It is envisaged that this
      system could be used as an assessment tool, providing a valuable aid to the SALT
      during clinical evaluation of voice quality.

PMID- 12237056
TI  - The use of glycerol-preserved allografts in the Beverwijk Burn Centre: a
      retrospective study.
AB  - This report describes 156 consecutive patients treated with glycerol-preserved
      allograft skin (GPA) in the Beverwijk Burn Centre between January 1996 and July
      2001. Patients with burn and non-burn lesions are included. Age varied from 7
      months to 90.7 years. Four different procedures have been identified: (1)
      sandwich grafting technique; (2) treatment of partial-thickness burns with GPA as
      a membranous dressing; (3) improvement of wound condition; (4) scar release: a
      temporary coverage of release incisions with allograft skin to improve the wound
      bed and to benefit further relaxation of the wound primary to autografting. The
      main points of interest in this inventory are the results of treatment, the
      aetiology and the extent of the wounds treated with GPA, the day post injury the
      GPA treatment was started, the duration of the treatment, the number of allograft
      applications, the occurrence of wound infection and wound treatment before GPA
      application. Concerning the scar release an inventory was made of the anatomic
      sites that were involved. Sandwich grafting, which is the treatment of choice at
      this centre for extensive, full-thickness injuries, was performed on 129 wounds.
      The average burn size in all 70 patients treated was 35.6% TBSA with 26.9% full
      thickness. In all cases meshed GPA was used. Partial or complete healing was
      achieved in 57.6% of wounds. In the treatment of partial-thickness burns, non
      meshed GPA was used in all 57 cases. Complete healing without further treatment
      was achieved in 45.6% of the cases. Excision and autologous skin grafting was
      needed in 26.3% of the cases. Meshed GPA was used to improve the condition of 88
      non-healing wounds. Spontaneous healing was promoted in 13.6% of the wounds, and
      the wound bed was successfully prepared for autografting in 39.8% of the cases.
      In all 52 scar releases a viable wound bed was obtained prior to autografting.
      Autologous graft take was 100% and no autologous re-grafting was necessary.
      Allografts in the popliteal space were changed most frequently.

PMID- 12237057
TI  - Clinical practice of glycerol preserved allograft skin coverage.
AB  - This retrospective study examines the use and advantages/disadvantages of
      glycerol preserved human allograft skin in our burn care facility between
      February 1997 and December 1999. Three hundred and twenty patients were included
      into the study, 85 of whom were treated with human cadaver skin. The usage of
      allograft slightly increased the number of operative procedures per percent of
      the total body surface area burn. There were no adverse effects noted from the
      use of allograft. The group of patients with allograft use had a significantly
      larger burn size, ABSI score and length of ICU stay. Demographically the groups
      were comparable. The considerably easier handling and storage of glycerol
      preserved allograft skin make it preferable to cryopreserved allograft skin in
      all indications where it is used as a temporary wound closure. We recommend the
      usage of cryopreserved skin in cases where the integration of a dermal component
      as a permanent part of wound closure is desired.

PMID- 12237058
TI  - The temporary use of allograft for complicated wounds in plastic surgery.
AB  - A retrospective analysis was performed on the use of glycerol-preserved
      allografts (GPA) in the preparation of complicated wounds for secondary wound
      closure. All files from the plastic surgery department in the period 1992-1998
      were screened. Thirty-three patients within a total 85 GPA treatments were
      selected and screened for indication of use of GPA, frequency of GPA changes,
      duration of treatment and whether or not subsequent autografting was possible.
      GPA was used as a biological cover for the following indications: problematic
      wound healing, 13 cases; non-healing burns, 12 cases; carcinoma, 4 cases;
      unstable scar, 2 cases; shortage of skin, 2 cases. The average frequency of GPA
      application was 2.6 times, with a mean duration of 5 days per application. In 84
      cases (32 patients) the wound was successfully covered with autograft. In
      conclusion, GPA was used with good results as a temporary cover for complicated
      wounds. We postulate that angiogenic effects of this biological dressing may have
      contributed to the improved healing conditions and successful secondary wound
      closure.

PMID- 12237059
TI  - A historical appraisal of the use of cryopreserved and glycerol-preserved
      allograft skin in the treatment of partial thickness burns.
AB  - Two studies into the use of allograft skin in the treatment of partial thickness
      burn injuries in this burn centre have provided the opportunity to discuss
      changes and similarities over a 20 year period. The first study described results
      obtained with cryopreserved allografts in partial thickness burns in the period
      1979-1981. The second study concerned patients with partial thickness injuries
      treated with glycerol-preserved allografts in the period 1998-2000. A reduction
      was noted concerning the need for secondary autografting in the group treated
      with glycerolized allografts. The probability that this difference has occurred
      by chance is small (P=0.089). Various other factors that might account for the
      differences in outcome, include general improvements in health and social
      welfare, differences in treatment protocols, and differences in allograft
      properties. A prospective comparative trial is indicated to study direct
      differences between the two types of allograft.

PMID- 12237060
TI  - Utilisation of glycerolised skin allografts in severe burns.

PMID- 12237061
TI  - Current indications for glycerol-preserved allografts in the treatment of burn
      injuries.

PMID- 12237062
TI  - Maintaining a glycerolized skin bank--a practical approach.
AB  - The Helsinki Burn Unit admits around 120-140 patients a year and, of these, 20-30
      need intensive care. Before 1995, fresh, non-tested cadaver skin was used to
      cover widely meshed autografts in large burns. In 1995, we founded a skin bank to
      avoid the problems encountered in the use of fresh cadaver skin: contamination by
      viruses or bacteria, shortage of available skin, the occasionally poor quality of
      the cadaver skin, and the inconvenience of harvesting skin in the mortuary.
      Crucial to the work of the Skin Bank has been cooperation with the
      Transplantation Unit of our hospital. This reduces paperwork and guarantees the
      quality of the donors. It also enables us to harvest skin only from tested
      multiorgan donors in an operating theater setting. Also important is a well
      organized team to ensure the procurement of a sufficient amount of good-quality
      allografts. This requirement raises the otherwise low costs of a glycerolized
      skin bank.

PMID- 12237063
TI  - Glycerolised allogenic skin: transplant or dressing? A medico-legal question.

PMID- 12237064
TI  - Postal survey on the use of glycerol-preserved allografts in clinical practice.
AB  - Glycerol-preserved allografts (GPAs) are in widespread use throughout Europe in
      the management of burns injury. However, little is known of the clinical usage
      and effectiveness of GPA. To gain more insight into clinical practice, The Euro
      Skin Bank (ESB), which is the main provider of GPA, sent a questionnaire to 62
      burn centres which had received GPA from the ESB in the last 5 years. Replies
      from 37 centres were received, of which 31 contained useful information. Ninety
      percent of correspondents used GPA regularly, although 24% of centres would
      prefer to use cryo-preserved allografts and 16% preferred fresh allografts. Three
      principal indications for GPA were identified: its use as a temporary cover on
      freshly excised wounds; its use as an overlay on widely expanded autografts and
      its use to improve the quality of the wound bed prior to autografting. Twenty
      five percent of correspondents used GPA as a biological dressing for partial
      thickness injuries.Pre-operative topical therapy consisted of semi-closed wound
      treatment with frequent dressing changes and application of silver sulfadiazine
      (SSD) or SSD with 1% cerium nitrate. Twenty percent of correspondents also used
      povidone iodine.The surgical approach of early excision and wound coverage
      (autograft or allograft) were followed by all correspondents. Graft fixation was
      achieved by staples alone or in combination with fibrin glue or adhesive
      dressings. Post-operative care comprised frequent dressing changes. Few
      clinicians used topical antibacterial agents and peri-operative antibiotics were
      prescribed by a third of correspondents. Few complications were reported
      following GPA use. Around 50% of clinicians reported "occasional" wound
      infection; around 50% of clinicians reported "occasional" graft failure. In
      general, GPA appeared to perform well in clinical practice.

PMID- 12237065
TI  - Treatment outcome in patients with mesial temporal sclerosis.
AB  - The long-term prognosis of pharmacological therapy in patients with mesial
      temporal sclerosis (MTS) is generally considered poor. On the contrary,
      successful surgical therapy is frequently reported. We performed a retrospective
      case record survey of patients with MTS in a comprehensive epilepsy center
      between 1993 and 1999 in order to develop treatment strategies. The time period
      allowed access to high-resolution qualitative magnetic resonance imaging (MRI)
      and a minimum of 1-year outcome assessment. Eighty-three patients with
      intractable partial epilepsy with MRI and electroencephalograph (EEG)
      abnormalities and seizure semiology consistent with temporal lobe epilepsy were
      identified. Thirty-six patients were treated pharmacologically and surgically and
      47 patients received only pharmacotherapy. The number of patients who became
      seizure free was in total 37 (45%); in the surgical group 26 and in the non
      surgical group 11. The proportions of seizure-free patients in each group were
      72% (surgical) and 23% (non-surgical). Clinical factors such as age, gender,
      lesion side, previous medical history, duration of illness, seizure frequency and
      IQ did not correlate to prognosis. A good seizure outcome was associated with
      early age of seizure onset, low number of previously used antiepileptic drugs
      (AEDs) and surgical treatment. There is a better long-term outcome in patients
      with MTS receiving surgical therapy in comparison with medical therapy.

PMID- 12237066
TI  - Analysis of gene expression in genetic epilepsy-prone rat using a cDNA expression
      array.
AB  - Our aim is to search the differential expression genes of genetic epilepsy and
      establish the groundwork of exploring the pathogenesis of epilepsy on the gene
      level by using cDNA array technology. METHODS: Gene expression profiles of the
      cerebral cortex of genetic epilepsy-prone P77PMC rats and normal Wistar rats were
      established using the Atlas Rat cDNA Expression Array. The difference between
      gene expression profiles was analyzed using an image analysis instrument.
      RESULTS: Fifteen genes exhibited a differential expression pattern between the
      P77PMC rats' and Wistar rats' cerebral cortex, while there maybe many other
      differential expression genes undiscovered due to having no image analysis
      software. Among them, the levels of expression of 13 genes were elevated in
      P77PMC rats as compared to their levels in Wistar rats, in contrast, the levels
      of expression of two genes were decreased in P77PMC rats. CONCLUSION: There were
      several differential expression genes between P77PMC rats and Wistar rats. All
      these genes could play important roles in the pathogenesis of epilepsy.

PMID- 12237068
TI  - Clinical expression and EEG features of patients with juvenile myoclonic epilepsy
      (JME) from North India.
AB  - We aimed to characterize the clinical profile, EEG features and response to
      treatment of juvenile myoclonic epilepsy (JME) patients. We studied 103 JME
      probands with a standard protocol recording age of onset, type, frequency of
      seizures, EEG data, detailed family history and response to treatment in a
      superspeciality university hospital in New Delhi. The mean age of onset of
      disease was 14.01 +/- 3.14 years with a male to female ratio of 1.19 : 1. The
      myoclonic jerks were present in all the probands, generalized tonic-clonic
      seizures (GTCS) were present in 75.72% and 11.65% probands had absence seizures.
      The incidence of febrile convulsion (FC) was higher (9.7%) in our JME probands
      reflecting some ethnic variation or ascertainment bias. There was a considerable
      delay (of approximately 5.26 +/- 4.61 years) in the diagnosis of JME in our
      probands because most of the patients were referred from private physicians who
      were possibly not familiar with this epileptic syndrome in this part of the world
      or thought it was a milder variety of GTCS. The family history was positive in
      25.24% JME probands among first- and second-degree relatives. An interictal EEG
      was found to be abnormal in 81 (78.64%) patients with the predominant abnormality
      being generalized polyspike and wave (PSW) discharges (39.80% probands). The
      majority of patients (80.58%) showed a good response to treatment with valproate
      alone. There was a subset of patients (11.65%) who required the addition of other
      antiepileptic drugs (AEDs) for control of GTCS: 7.76% of JME patients were
      diagnosed as cases of GTCS by private practitioners before they were registered
      in our study and their seizures were well controlled on other AEDs (without
      valproate) prescribed by the referring physicians (carbamazepine-4, phenytoin-2,
      clobazam-2). It is concluded that the clinical features and EEG data of JME
      probands were comparable to reports from other parts of the world except for the
      fact that the incidence of FC was higher in our JME patients. There was a delay
      in the diagnosis of JME due to unfamiliarity with the epileptic syndrome among
      private practitioners in this part of the world. There was a subset of JME
      patients who had complete seizure control on other AEDs besides valproate.

PMID- 12237067
TI  - Anticonvulsant and antiepileptogenic effects of fluorofelbamate in experimental
      status epilepticus.
AB  - PURPOSE: To examine the seizure-protective properties of fluorofelbamate, a
      felbamate analog, on acute and chronic seizures in an experimental model of self
      sustaining status epilepticus (SSSE). METHODS: SSSE was induced by stimulation of
      the perforant path for 30 min (PPS) through chronically implanted electrodes in
      free-running adult male Wistar rats. Fluorofelbamate was injected intravenously
      (i.v.) either 10 min, or 40 min after SSSE induction. Seizure and spike profiles
      were analyzed off-line. RESULTS: Fluorofelbamate injected during the early stages
      of SSSE (10 min after the end of PPS), shortened the duration of seizures in a
      dose-dependent manner. While a dose of 50 mg kg(-1) was ineffective, 100 and 200
      mg kg(-1) reduced cumulative seizure time from 393 +/- 10 min to 15 +/- 8 min and
      2.4 +/- 0.5 min respectively. Administration of fluorofelbamate (200 and 300 mg
      kg (-1)) at a late stage of SSSE, which is refractory to treatment with
      conventional anticonvulsants, also significantly attenuated seizures. Acute
      fluorofelbamate treatment (200 mg kg(-1) 10 min after PPS) significantly
      decreased the frequency of spontaneous seizures which follow SSSE after a
      'latent' interval. Moreover, in contrast to control animals, fluorofelbamate
      treated rats showed regression of spontaneous seizures, and an apparent remission
      of epilepsy within 2 months after SSSE. CONCLUSIONS: Acute treatment of SSSE with
      fluorofelbamate showed strong anticonvulsant effects even during the late stages
      of SSSE. In this model, it also displayed antiepileptogenic properties: it
      reduced the severity of chronic epilepsy after SSSE and lead to apparent
      remissions of that epilepsy.

PMID- 12237069
TI  - Epilepsia partialis continua--a clinical and electroencephalography study.
AB  - Epilepsia partialis continua (EPC) is a rare type of localization-related motor
      epilepsy. Clinical spectrum, electroencephalography (EEG) characteristics and
      various prognostic factors in EPC were studied in 20 patients. Patients who
      fulfilled the criteria for EPC between the years 1985 and 1999 were included in
      this retrospective and prospective study. The mean age was 18 years (range 5
      months-70 years). Eleven patients (55%) had Type 1 EPC and in the remaining nine
      (45%) patients there were features of Type 2 EPC. Among children Rasmussen's
      encephalitis and viral encephalitis were the commonest cause for EPC.
      Encephalitis and vascular aetiology were frequently observed in adults.
      Tuberculous meningitis and tuberculomas occurred evenly in both the groups. The
      cause was unknown in two cases. Focal EEG abnormalities commonly consisted of
      discrete spikes, sharp waves (or) slow wave activity and periodic lateralized
      epileptiform discharges. The mean duration of follow up was 9.6 months with a
      range between 1 month and 4 years. Cognitive decline, motor deficits and
      pharmacoresistance to drugs were significantly seen among children with Type 2
      EPC. Patients with Type 1 EPC had mild impairment of functional status with good
      response to treatment. The long-term prognosis depends upon the underlying cause.

PMID- 12237070
TI  - Hemispheric predominance of abnormal findings in electroencephalogram (EEG).
AB  - The EEGs of 13,560 patients have been reviewed in order to determine whether
      abnormal findings, epileptiform or not, have a hemispheric dominance. We have
      included outpatients and hospitalized patients as well. Eight hundred and thirty
      five EEGs had generalized abnormal findings, and 414 EEGs had lateralized
      abnormal findings. The EEGs of 322 patients (77.7%) had a left predominance, and
      those of 92 patients (22.3%) had a right predominance, of abnormal findings. A
      strong left predominance has been noted for the epileptiform discharges, i.e. 128
      (79%) vs. 34 (21%). These results raise the possibility that the left hemisphere
      may be more vulnerable to nosological processes.

PMID- 12237071
TI  - Letter to the editor. Discordant twins for neural tube defect on treatment with
      sodium valproate.

PMID- 12237072
TI  - Sudden unexplained death in epilepsy (SUDEP) following previous seizure-related
      pulmonary oedema: case report and review of possible preventative treatment.
AB  - We report a seizure-related death in a patient with juvenile myoclonic epilepsy 3
      months following a previous generalised tonic-clonic seizure complicated by
      pulmonary oedema. Seizure-related pulmonary oedema is rare but may indicate an
      increased susceptibility to epilepsy related death. We consider possible
      preventative measures for patients presenting with seizure-related pulmonary
      oedema.

PMID- 12237073
TI  - Nonconvulsive status epilepticus presenting as a subacute progressive aphasia.
AB  - We report a 62-year-old man with non-convulsive status epilepticus (NCSE)
      presenting as a progressive aphasia that developed insidiously over 5 weeks. On
      video-EEG monitoring, aggravation of the aphasia coincided with occurrence of
      seizure activities arising from the left fronto-temporal area. Brain MRI was
      noncontributory but a fluorodeoxyglucose-PET scan revealed a hypometabolism in
      the left anterior temporal area. Following anticonvulsant treatment, aphasia
      recovered gradually over several weeks despite prompt resolution of epileptic
      discharges on EEG. Our patient's findings, gradual onset of isolated aphasia with
      gradual resolution after initiation of treatment, may differ from previously
      reported cases with aphasic status epilepticus because their aphasia showed
      abrupt onset and rapid resolution with anticonvulsant medication.

PMID- 12237074
TI  - Pilomotor seizures: symptomatic vs. idiopathic report of two cases and literature
      review.
AB  - We report pilomotor seizures in two patients who presented with piloerection or
      gooseflesh spreading in a pattern similar to the 'Jacksonian march'. Gooseflesh
      was confined to the ipsilateral side in most of the episodes. Occasionally it
      spread to the contralateral side. It was also associated with other autonomic
      symptoms and complex partial features of temporal lobe origin. Simple partial
      status that progressed to complex partial status occurred in the second patient.
      Very rarely secondary generalization occurred. The cause was left sphenoid
      meningioma and temporal tip contusion in the first case. It was idiopathic in the
      second case, although a positive family history of complex partial seizures was
      obtained in this patient. Interictal electroencephalogram (EEG) showed left
      temporal focus in the first and bitemporal foci with right fronto-temporal
      dominance in the second. Parenteral phenytoin controlled the partial complex
      status in the second and carbamazepine controlled the episodes in both cases. To
      our knowledge all reported cases were symptomatic and our case of idiopathic
      aetiology is the first to be recorded. We endorse that pilomotor seizures are
      autonomic in nature and constitute a subtype of simple partial seizures. These
      autonomic simple partial seizures may progress to, or be a component of, complex
      partial seizures of temporal lobe origin. Based on their dominance in such a
      symptom complex and careful interpretation of the ictal history, it can be
      logically concluded that pilomotor seizures may be underestimated by both
      patients and physicians.

PMID- 12237075
TI  - Reversible hemiparesis associated with the use of topiramate.
AB  - We report a case of a 5-year-old boy with intractable partial seizures who
      developed a transient hemiparesis, worsening of the electroencephalogram (EEG)
      and a change in his seizure pattern with increased seizure frequency after
      receiving topiramate (TPM). Symptoms resolved within a month after TPM was
      discontinued. Clinicians need to be aware that TPM use may occasionally be
      associated with focal motor weakness and exacerbation of seizures.

PMID- 12237076
TI  - Interaction of topiramate with carbamazepine: two case reports and a review of
      clinical experience.
AB  - We describe a possible clinical interaction between topiramate (TPM) and
      carbamazepine modified release (CBZ-MR) in patients taking maximum tolerated
      doses of carbamazepine. Data are presented on 25 patients who contacted the
      epilepsy nurse specialist telephone helpline for advice after starting treatment
      with TPM. Thirteen male and 12 female patients, mean age 41 years (range 25-69
      years), with localization-related epilepsy contacted the helplines, between
      November 1999 and March 2001, complaining of symptoms of antiepileptic drug
      intoxication after starting treatment with TPM. All were taking maximum tolerated
      doses of CBZ-MR before starting TPM. Sixteen of the patients were taking other
      antiepileptic drugs concomitantly with CBZ-MR and TPM. Symptoms of intoxication
      were similar to those previously experienced when maximum tolerated doses of CBZ
      MR were exceeded. Symptoms resolved when concomitant CBZ-MR doses were reduced,
      enabling further dose escalation of TPM. To our knowledge, neither clinical nor
      pharmacological interactions between CBZ and TPM have been described previously
      in man. These data suggest that such an interaction may be of clinical
      importance, and that reduction of the CBZ dose may enable optimization of the
      dose of TPM, improving seizure control.

PMID- 12237077
TI  - Selective mutism and obsessive compulsive disorders associated with zonisamide.
AB  - We treated 27 children with idiopathic epilepsy with zonisamide monotherapy over
      a period of 2 years and observed behaviour disturbances in a prospective study.
      In all cases, seizure control was excellent; however, two cases (7.4%) had
      behaviour disturbances. The first (Case 1) was a 14-year-old girl with partial
      epilepsy which began at age 4 years. Zonisamide was administered at age 6 years,
      which was effective against her seizures, but selective mutism, violent
      behaviour, and lack of concentration developed at age 10 years. The second (Case
      2) was a 15-year-old girl with generalized tonic-clonic seizures which began at
      age 10 years. Zonisamide was also effective against her seizures, but obsessive
      compulsive disorders (OCD) developed at age 13 years. The patients have had no
      other physical or mental problems and decreasing the dosage of zonisamide reduced
      the problems. There are few reports of behaviour disturbances provoked by
      zonisamide monotherapy in epileptic children who are neither physically nor
      mentally disturbed. While problems can develop several years later, in the
      present study, decreasing the zonisamide dosage maintained adequate prevention of
      seizures and eliminated the behaviour disturbances. Zonisamide is still a useful
      anticonvulsant for epileptic seizures, but physicians should be wary of its
      adverse behavioural side effects, which may arise several years later.

PMID- 12237079
TI  - New developments in tetracycline antibiotics: glycylcyclines and tetracycline
      efflux pump inhibitors.
AB  - The tetracyclines, discovered in the 1940s, are a well-established class of
      antibiotics that still have a role in treating microbial infections in man.
      However, the widespread emergence of bacterial resistance due to efflux and
      ribosomal protection mechanisms has severely limited their effectiveness. A new
      generation of tetracyclines, the glycylcyclines, has been developed to overcome
      resistance to earlier tetracyclines. One of the new glycylcyclines, 9-t
      butylglyclamido-minocycline (GAR-936, tigecycline) is currently undergoing
      clinical trials. This review considers the current status of glycylcyclines and
      the possibility that resistance to these agents might arise in the future. Other
      approaches are also being taken to address the emergence of resistance to
      tetracyclines. Recently, a number of tetracycline efflux pump inhibitors have
      been discovered that might be used in combination with earlier tetracyclines to
      restore their activity against resistant organisms. However, the development of
      tetracycline efflux pump inhibitors is complicated by the occurrence of several
      efflux pump sub-families and by the presence of both efflux and ribosomal
      protection mechanisms in the same organism, especially in naturally occurring,
      Gram-positive clinical isolates.

PMID- 12237080
TI  - Transfection technology and the study of drug resistance in the malaria parasite
      Plasmodium falciparum.
AB  - Numerous approaches have been employed to identify the molecules responsible for
      drug resistance in the human malaria parasite Plasmodium falciparum. However, it
      was not until the recent development of stable transfection in this parasite that
      it became possible to prove the role of particular genes in drug resistance and,
      perhaps more importantly, to characterise the nature of the specific mutations
      that contribute the resistance phenotype. In this review, the contribution of
      various molecular genetic approaches to the dissection of drug resistance in P.
      falciparum is described. Future possibilities in this field are also outlined in
      the light of recent technological advances.

PMID- 12237081
TI  - Role of X-linked inhibitor of apoptosis protein in chemoresistance in ovarian
      cancer: possible involvement of the phosphoinositide-3 kinase/Akt pathway.
AB  - Although cisplatin derivatives are first-line chemotherapeutic agents for the
      treatment of epithelial ovarian cancer, chemoresistance remains a major hurdle to
      successful therapy and the molecular mechanisms involved are poorly understood.
      Apoptosis is the cellular underpinning of cisplatin-induced cell death, which is
      associated with expression of specific "death" genes and down-regulation of
      "survival" counterparts. The X-linked inhibitor of apoptosis proteins (Xiap), an
      intracellular anti-apoptotic protein, plays a key role in cell survival by
      modulating death signaling pathways and is a determinant of cisplatin resistance
      in ovarian cancer cells in vitro. This review focuses on the role of Xiap and its
      interactions with the phosphoinositide-3 kinase (PI3K)/Akt cell survival pathway
      in conferring resistance of ovarian cancer cells to chemotherapeutic agents and
      discusses potential therapeutic strategies in overcoming chemoresistant ovarian
      cancer.

PMID- 12237082
TI  - Molecular aspects of resistance to antitumor platinum drugs.
AB  - The processes by which cells develop resistance to antitumor platinum drugs have
      been the subject of intense research because resistance is a major obstacle for
      the clinical use of this class of drugs. It is therefore of great interest to
      understand the molecular and biochemical mechanisms that underlie resistance to
      platinum drugs and their biological effects. There is a large body of
      experimental evidence suggesting that the antitumor activity of platinum
      complexes stems from their ability to form on DNA various types of covalent
      adducts. As a result, research on DNA modifications by these drugs and their
      cellular processing has predominated. The resistance of tumor cells to platinum
      drugs has been attributed to several processes and an increased repair of
      platinum-DNA adducts is considered a most significant event. The present review
      summarizes recent insights into the effects of sulfur-containing compounds on DNA
      modifications by antitumor platinum complexes and how these modifications are
      repaired including how this repair is associated with their recognition by
      cellular, damaged-DNA binding-proteins. It strongly supports the view that
      changes in the structure of platinum drugs, resulting in DNA binding mode
      fundamentally different from that of "classical" cisplatin, will alter resistance
      pathways of platinum drugs, and may also modulate their pharmacological
      properties.

PMID- 12237083
TI  - Retinoids in combination therapies for the treatment of cancer: mechanisms and
      perspectives.
AB  - Retinoid derivatives have been of special interest in cancer research because of
      their antiproliferative and differentiation-inducing activities in premalignant
      and malignant cells. Some retinoids are clinically effective in cancer therapy
      and prevention, and all-trans-retinoic acid is being used for the treatment of
      acute promyelocytic leukemia. Unfortunately, classical retinoids are not
      effective against most advanced solid tumors and cause undesirable side effects,
      which have limited the full development of retinoids as chemopreventive and
      chemotherapeutic drugs. The recent identification of selective retinoid
      derivatives capable of inducing apoptosis and their combination with other
      anticancer therapies promises a more effective and less toxic manner to the
      successful use of retinoids in cancer therapy.

PMID- 12237084
TI  - The point of maximum cell water volume excursion in case of presence of an
      impermeable solute.
AB  - A relativistic permeability model of cell osmotic response (Cryobiology 40:64-83;
      41:366-367) is applied to a two-solute system with one impermeable solute. The
      use of the normalized water volume (w), and the amount of intracellular permeable
      solute (x), which is the product of the water volume and intracellular osmolality
      (y), as the main variables allowed us to obtain a homogeneous differential
      equation dx(Delta)/dw(Delta)=f(x(Delta)/w(Delta)), where w(Delta)=w-w(f),
      x(Delta)=x-x(f), and f refers to the final (equilibrium) values. The solution of
      this equation is an explicit function, w(Delta)=g(x(Delta)), which is given in
      the text. This approach allows us to obtain an analytical (exact) expression of
      the water volume at the moment of the maximum excursion (water extremum w(m)).
      Results are compared with numeration of basic osmotic equations and with
      approximation given in (Cryobiology 40:64-83). Assumption that, dw/dt
      approximately 0 gives good approximations of the kinetics of water and permeable
      CPA after the point of maximum volume excursion (the slow phase of osmotic
      response). Practical aspects of the relativistic permeability approach are also
      discussed.

PMID- 12237085
TI  - Analytical solution for the extremums of cell water volume and cell volume using
      a two-parameter model.
AB  - Based on a two-parameter model [Cryobiology 37 (1998) 271-289], the analytical
      solution for the extremums of cell water volume and cell volume for a two-solute
      system are obtained. Compared with the numerical solution, the analytical
      solution offers an accurate but simple choice. The approximate solution
      [Cryobiology 40 (2000) 64-83] for the extremum of cell water volume is also
      discussed, the reason for the deviation is presented.

PMID- 12237086
TI  - Cryopreserved human haematopoietic stem cells retain engraftment potential after
      extended (5-14 years) cryostorage.
AB  - Harvesting of stem cells during the early phases of treatment with no immediate
      intention to perform a stem cell transplant is becoming an increasingly common
      practice. Such "insurance" harvests are often stored for many years before being
      needed for transplant in a subsequent relapse. The effect of long-term
      cryostorage (5-14 years) on the viability and functional capacity of
      haematopoietic stem cells (HSCs) was investigated in 40 bone marrow and
      peripheral blood harvests using standard in vitro methods, the colony forming
      unit-granulocyte/macrophage (CFU-GM) assay and a single platform viable CD34(+)
      cell absolute count by flow cytometry. Forty percent of harvests had CD34(+) HSC
      counts of at least 0.7 x 10(6)/kg bodyweight and 85% had CFU-GM counts of at
      least 1.0 x 10(5)/kg bodyweight, these values representing our institutional
      minimum requirements for safe transplantation. Based on these results, it appears
      that HSC collections can remain adequate for safe transplantation after up to 14
      years of cryostorage. However, as deterioration of HSC quality and viability may
      occur, some precautions may be warranted, namely harvesting higher than normal
      numbers of HSCs in collections intended for long-term storage and repeating in
      vitro assays on harvests after long-term storage prior to transplantation.

PMID- 12237087
TI  - Cryopreservation of fetal skin is improved by extracellular trehalose.
AB  - In this study, we tested a non-permeating cryoprotectant, trehalose, in
      combination with dimethyl sulfoxide (Me(2)SO) in the cryopreservation of human
      fetal skin and compared it to Me(2)SO and glycerol, protocols that are routinely
      used by skin banks. The viability of fetal skin from four groups (fresh, and
      cryopreserved with glycerol, Me(2)SO, or trehalose/Me(2)SO) were evaluated using
      an in vitro membrane integrity assay and by transplantation to immunodeficient
      mice. The membrane integrity assay showed a 90% integrity in fresh, unfrozen
      fetal skin. The number of intact cells dropped to 23 and 44% in fetal skin
      cryopreserved with glycerol and Me(2)SO, respectively. When trehalose was added
      to the cryopreservation medium containing Me(2)SO, the membrane integrity rose to
      65%. When transplanted to immunodeficient mice, fetal skin cryopreserved with
      trehalose/Me(2)SO showed a graft performance indistinguishable from fresh
      unfrozen fetal skin and strikingly better graft take than that of fetal skin
      cryopreserved with Me(2)SO or glycerol only. These results suggest that
      cryopreservation protocols routinely used the skin banks can be improved by
      combining sugars such as trehalose with a permeating cryoprotectant.

PMID- 12237088
TI  - Effects of extender composition, cooling rate, and freezing on the motility of
      sea bass (Dicentrarchus labrax, L.) spermatozoa after thawing.
AB  - A successful cryopreservation procedure for sperm must guarantee recovery of the
      morphological and functional characteristics of the cells following thawing so
      that preserved semen can to be used comparably with non-preserved semen. The aim
      of this work was to identify a species-specific freezing protocol for sea bass
      (Dicentrarchus labrax) spermatozoa by optimising all the stages in the
      cryopreservation procedure. In the first stage of the experiments, the
      cryoprotectants and the relative concentrations that had the least toxic effect
      on motility at room temperature were selected. The capacity of the selected
      cryoprotectant substances was then assessed in freezing tests as follows:
      dimethyl sulfoxide (Me(2)SO) 5% and 7%, ethylene glycol (EG) 7% and 10%,
      propylene glycol (PG) 7% and 10%. The cryoprotectant that gave the best results
      in this second stage of the experiments was EG 10%, and this was then used for
      the optimisation of the different stages in the freezing procedure: two different
      times of adaptation to the cryoprotectant were tested (15min and 6h), as well as
      the effects of adding an energy substrate (1.25mM sodium pyruvate) to assess its
      possible use as an energy source. Lastly, using the extender (diluent+Na
      pyruvate+EG10%) and the adaptation procedure (6h at 0-2 degrees C) that had given
      the best results in the preceding stages of the experiments, four cooling rates
      were tested: 10, 12, 15, 24 degrees C/min. It was shown that the semen that was
      diluted immediately after collection in extender that contained the
      cryoprotectant (EG 10%), was equilibrated for 6h at 0-2 degrees C and then cooled
      at a rate of 15 degrees C/min, showed motility on thawing comparable to that of
      fresh semen (P=0.045).

PMID- 12237089
TI  - Hexagonal shaped ice spicules in frozen antifreeze protein solutions.
AB  - In the presence of antifreeze proteins from both Antarctic and Arctic fishes,
      water freezes in the form of long c-axis spikes or spicular-like crystals.
      Transmission electron microscopy of the Pt/C replicas of the freeze fractured
      spicular ice in a small capillary revealed the presence of many hexagonally
      shaped structures whose cross-sectional dimensions were between 0.5 and 10
      microm. Well-defined parallel faces were associated with most fractured and
      etched spicules. When fracture planes occurred near the tip of a spicule, well
      defined pyramidal faces were apparent. Steps were sometimes associated with these
      pyramidal spicular crystal faces. On some of the replicas obvious roughening of
      certain crystal faces of the spicule was observed, suggesting that the antifreeze
      proteins may have adsorbed to those faces.

PMID- 12237090
TI  - A comparison of sucrose, saline, and saline with egg-yolk diluents on the
      cryopreservation of cane toad (Bufo marinus) sperm.
AB  - Previous studies on cane toad (Bufo marinus; Bufonidae; Anura) sperm
      cryopreservation were extended to compare the effects of cryopreservation in
      established sucrose (non-ionic) diluents with cryopreservation in ionic diluents
      containing amphibian Ringer solutions (with and without egg-yolk). In addition,
      methanol was tested as a cryoprotectant for B. marinus sperm for the first time.
      Twenty-seven cryoprotective solutions were trialled, with each containing one of
      the three diluents [10% (w/v) sucrose, simplified amphibian Ringer (SAR) or
      SAR/egg-yolk], with one of the three cryoprotectants (Me(2)SO, glycerol, or
      methanol) at one of the three concentrations (10%, 15%, or 20% v/v). Sperm were
      collected by maceration of testes into cryoprotective solutions with post-thaw
      recovery assessed as the percentage of motile sperm and the degree (vigour) of
      motility. Percentage motility was the most sensitive measure of post-thaw
      recovery. The recovery of motility was lowest in Ringer (SAR) diluents and
      highest in sucrose diluents, with improved motility in SAR diluents when egg-yolk
      was added. Methanol was the poorest cryoprotectant and Me(2)SO the most
      effective. Methanol at high concentrations was shown to support recovery in
      sucrose diluent but not in SAR, although its effectiveness in SAR was improved by
      egg-yolk. Overall, the efficacy of diluents in supporting a high percentage of
      sperm recovery was in declining order: sucrose>SAR/egg-yolk>SAR diluents, and
      with cryoprotectants: Me(2)SO>glycerol>methanol. In conclusion, SAR offers less
      potential as a diluent than sucrose, presumably due to the presence of inorganic
      ions.

PMID- 12237091
TI  - Canine RBC osmotic tolerance and membrane permeability.
AB  - The objective of this study was to determine the cryobiological characteristics
      of canine red blood cells (RBC). These included the hydraulic conductivity
      (L(p)), the permeability coefficients (P(s)) of common cryoprotectant agents
      (CPAs), the associated reflection coefficient (sigma), the activation energies
      (E(a)) of L(p) and P(s) and the osmotic tolerance limits. By using a stopped-flow
      apparatus, the changes of fluorescence intensity emitted by intracellularly
      entrapped 5-carboxyfluorescein diacetate (CFDA) were recorded when cells were
      experiencing osmotic volume changes. After the determination of the relationship
      between fluorescence intensity and cell volume, cell volume changes were
      calculated. These volume changes were used in three-parameter fitting
      calculations to determine the values of L(p), P(s), and sigma for common CPAs.
      These volume measurements and data analyses were repeated at three different
      temperatures (22, 14, 7 degrees C). Using the Arrhenius equation, the activation
      energies of L(p) and P(s) in the presence of CPAs were determined. The osmotic
      tolerance limits for canine RBC were determined by measuring the percentage of
      free hemoglobin in NaCl solutions with various osmolalities compared to that
      released by RBC incubated in double distilled water. The upper and lower osmotic
      tolerance limits were found to be 150mOsm (1.67V(iso)) and 1200mOsm (0.45V(iso)),
      respectively. These parameters were then used to calculate the amount of non
      permeating solute needed to keep cell volume excursions within the osmotic
      tolerance limits during CPA addition and removal.

PMID- 12237092
TI  - Ischemic preconditioning in a rodent hepatocyte model of liver hypothermic
      preservation injury.
AB  - Ischemic preconditioning (IPC) is a phenomenon of protection in various tissues
      from normothermic ischemic injury by previous exposure to short cycles of
      ischemia-reperfusion. The ability of IPC to protect hepatocytes from a model of
      hypothermic transplant preservation injury was tested in this study. Rat
      hepatocytes were subjected to 30min of warm ischemia (37 degrees C) followed by
      24 or 48h of hypothermic (4 degrees C) storage in UW solution and subsequent re
      oxygenation at normothermia for 1h. Studies were performed with untreated control
      cells and cells treated with IPC (10min anoxia followed by 10min re-oxygenation,
      1 cycle). Hepatocytes exposed to IPC prior to warm ischemia released
      significantly less LDH and had higher ATP concentrations, relative to untreated
      ischemic hepatocytes. IPC significantly reduced LDH release after 24h of cold
      storage before reperfusion and after 48h of cold storage and after 60min of warm
      re-oxygenation, relative to the corresponding untreated hepatocytes. ATP levels
      were also significantly higher when IPC was used prior to the warm and cold
      ischemia-re-oxygenation protocols. In parallel studies, IPC increased new protein
      synthesis and lactate after cold storage and reperfusion compared to untreated
      cells but no differences in the patterns of protein banding were detected on
      electrophoresis between the groups. In conclusion, IPC significantly improves
      hepatocyte viability and energy metabolism in a model of hypothermic preservation
      injury preceded by normothermic ischemia. These protective effects on viability
      may be related to enhanced protein and ATP synthesis at reperfusion.

PMID- 12237093
TI  - A new bone banking technique to maintain osteoblast viability in frozen human
      iliac cancellous bone.
AB  - The aim of this study was to develop a new cryopreservation technique to maintain
      the osteoblast viability in frozen iliac bone and to prove cell viability using
      cell culture techniques. Human iliac cancellous bones were frozen with and
      without 10% Me(2)SO at -80 degrees C. The tubes were kept in a -80 degrees C
      freezer for at least 2 days. After the storage period, the frozen bone was thawed
      by placing the tube in a 37 degrees C water bath. A serial enzymatic digestion
      technique using 0.2% collagenase was employed to isolate osteoblast-like cells
      from the bone. The cells that were released were inoculated into tissue culture
      flasks containing DMEM supplemented with 10% FCS. They were incubated at 37
      degrees C in a humidified atmosphere of 95% air and 5% CO(2). Cells of the second
      passage were plated at a density of 5 x 10(3)cells/cm(2) in a 24-well plate and
      used for characterization. For characterization, WST-1 assay, determination of
      alkaline phosphatase, Type I collagen assay, osteocalcin assay, and von Kossa
      staining were used. The assays were performed at 3, 6, 9, and 12 days after
      plating the cells. Based on the results of this study, we conclude that the
      osteoblast-like cells in the frozen bone can survive, only when the bone is
      frozen with cryoprotectants to prevent injury during freezing and thawing.

PMID- 12237094
TI  - Osmotic properties of spermatozoa from felids producing different proportions of
      pleiomorphisms: influence of adding and removing cryoprotectant.
AB  - The spermatozoon of felids (cats) survives cryopreservation inconsistently. Using
      ejaculates from three species (domestic cat [normospermic versus teratospermic],
      the normospermic serval and the teratospermic clouded leopard), this study (1)
      determined the influence of adding and removing two permeating cryoprotectants
      (glycerol and dimethylsulfoxide) and (2) assessed the impact of one-step versus
      multi-step cryoprotectant removal on sperm motility and membrane integrity.
      Spermatozoa were exposed in a single step to various anisotonic solutions or to
      1M solutions of glycerol or dimethylsulfoxide. In both cases, sperm then were
      returned to near isotonic conditions in a single or multi-step with de-ionized
      water, Ham's F10 medium or saline. Percentage of sperm motility was measured
      subjectively, and plasma membrane integrity was assessed using a dual fluorescent
      stain and flow cytometry. Sperm motility was more sensitive to anisotonic
      conditions than membrane integrity. Rapid dilution into various test solutions
      and removal of cryoprotectant with de-ionized water reduced (P<0.01) sperm
      motility compared to control spermatozoa maintained in Ham's F10. Exposing sperm
      from all species to a 1M solution of either cryoprotectant resulted in >85%
      spermatozoa retaining intact membranes. However, return to isotonicity with de
      ionized water in a single step or multiple steps always caused severe plasma
      membrane disruption. In contrast, sperm motility and membrane integrity in all
      species and populations remained unaffected (P>0.05) when spermatozoa were
      returned to isotonicity in multiple steps with Ham's F10 medium or 0.9% sodium
      chloride. Results demonstrate that: (1) felid spermatozoa are resistant to
      hypertonic stress; (2) sperm motility is more sensitive to changes in osmolality
      than membrane integrity; and (3) removal of cryoprotectant in multiple steps with
      an isotonic solution minimizes loss of sperm motility and membrane disruption in
      both normospermic and teratospermic males.

PMID- 12237095
TI  - The glass transition temperature of mixtures of trehalose and hydroxyethyl
      starch.
AB  - Although mixtures of HES and sugars are used to preserve cells during freezing or
      drying, little is known about the glass transition of HES, or how mixtures of HES
      and sugars vitrify. These difficulties may be due to the polydispersity between
      HES samples or differences in preparation techniques, as well as problems in
      measuring the glass transition temperature (T(g)) using differential scanning
      calorimetry (DSC). In this report, we examine the T(g) of mixtures of HES and
      trehalose sugar with <1% moisture content using DSC measurements. By
      extrapolating these measurements to pure HES using the Gordon-Taylor and Fox
      equations, we were able to estimate the T(g) of our HES sample at 44 degrees C.
      These results were additionally confirmed by using mixtures of glucose-HES which
      yielded a similar extrapolated T(g) value. Our approach to estimating the glass
      transition temperature of HES may be useful in other cases where glass
      transitions are not easily identified.

PMID- 12237096
TI  - The stability during low-temperature storage of an antifreeze protein isolated
      from the roots of cold-acclimated carrots.
AB  - Natural antifreeze proteins (AFPs) not only inhibit freezing at high subzero
      temperatures; they have the additional properties of inhibiting the
      recrystallization of ice during warming and of preventing devitrification. The
      natural AFP that occurs in the roots of cold-acclimated carrots can be extracted
      reasonably simply and is non-toxic: it was selected for study as a possible
      ingredient of the vitrification mixtures that are being developed for use in
      tissue cryopreservation. For this application, it would be essential for the AFP
      to remain active during prolonged storage at very low temperatures. For logistic
      reasons, it would also be essential to have an effective method of storage of the
      purified AFP itself. In this study, carrot AFP was isolated and purified, and its
      ability to inhibit recrystallization was monitored over 40 weeks of storage at 
      80 or -196 degrees C. The data revealed a progressive decrease in activity during
      storage, reaching half the original activity in 10-20 weeks and only 2-3% of the
      original activity at 40 week. These data suggest that carrot AFP will not be
      effective in tissue cryopreservation.

PMID- 12237097
TI  - Greed takes over "our" yeast genome sequence.

PMID- 12237098
TI  - Redox- and oxidant-mediated regulation of interleukin-10: an anti-inflammatory,
      antioxidant cytokine?
AB  - Reduction-oxidation (redox) state constitutes such a potential signaling
      mechanism for the regulation of an inflammatory signal associated with oxidative
      stress. Interleukin (IL)-10 has recently emerged as an anti-inflammatory cytokine
      with antioxidant properties. Interestingly, redox- and oxidant-mediated pathways
      positively and/or negatively regulate the expression, distribution, and
      functional properties of IL-10, thus, allowing the evolution of what is known as
      an anti-inflammatory redox-oxidant revolving axis. This axis is directly involved
      in regulating phosphorylation mechanisms, which eventually control gene
      expression and the biosynthesis of oxidative stress-related cofactors, such as
      reactive species and inflammatory cytokines. The association between IL-10, an
      anti-inflammatory antioxidant, with redox- and oxidant-related pathways governing
      the regulation of inflammatory and closely dependent processes is thereafter
      discussed.

PMID- 12237099
TI  - Differentiation of embryonic stem cells into retinal neurons.
AB  - Mouse embryonic stem (ES) cells are continuous cell lines derived from the inner
      mass of blastocysts. Neural progenitors derived from these cells serve as an
      excellent model for controlled neural differentiation and as such have tremendous
      potential to understand and treat neurodegenerative diseases. Here, we
      demonstrate that ES cell-derived neural progenitors express regulatory factors
      needed for retinal differentiation and that in response to epigenetic cues a
      subset of them differentiate along photoreceptor lineage. During the
      differentiation, they activate photoreceptor regulatory genes, suggesting that ES
      cell-derived neural progenitors recruit mechanisms normally used for
      photoreceptor differentiation in vivo. These observations suggest that ES cells
      can serve as an excellent model for understanding mechanisms that regulate
      specification of retinal neurons and as an unlimited source of neural progenitors
      for treating degenerative diseases of the retina by cell replacement.

PMID- 12237100
TI  - Induction of apoptosis and inhibition of cell growth by developmental regulator
      hTBX5.
AB  - T box (Tbx) genes are a large family of transcription regulators that play
      critical roles in invertebrate and vertebrate development. Mutations in Tbx5 gene
      have been found to cause Holt-Oram syndrome (HOS) in humans. Partial dysfunction
      of TBX5 in mouse also causes HOS phenotype. Little is known about its molecular
      and cellular mechanism. Here, we report that ectopic expression of TBX5 inhibited
      colony formation, induced apoptosis, and decreased the growth rate of cells. The
      two point mutations in T domain and a truncated mutation in C-terminal found in
      human HOS patients produced TBX5 mutant proteins with a significantly reduction
      of colony suppression activity. Deletion of the DNA-binding domain, however,
      nearly completely abrogated its ability to suppress colony formation. These
      results reveal TBX5 as a new regulator of apoptosis and cell growth, suggesting a
      possible mechanism for Holt-Oram syndrome, and a potential reagent for
      controlling tumor growth.

PMID- 12237102
TI  - Stereoselective hydroxylation of 4-methyl-2-cyclohexenone in rats: its relevance
      to R-(+)-pulegone-mediated hepatotoxicity.
AB  - R-(+)-Pulegone, a monoterpene ketone, is a potent hepatotoxin. One of the major
      metabolites of pulegone has been shown to be p-cresol, a glutathione depletor and
      a known toxin. Allylic hydroxylation of 4-methyl-2-cyclohexenone results in the
      formation of p-cresol. The present study documents for the first time the
      involvement of cytochrome P-450 system and the stereochemical preference in this
      hydroxylation reaction. Incubation of PB-induced rat liver microsomes as well as
      reconstituted PB-induced cytochrome P-450 system with +/-4-methyl-2-cyclohexenone
      in the presence of NADPH and O(2) resulted in the formation of 4-hydroxy-4-methyl
      2-cyclohexenone and p-cresol. From the assay mixture, the unreacted substrate,
      viz., 4-methyl-2-cyclohexenone was isolated and purified and its optical rotation
      was found to be 2.2 (in CHCl(3)). The observed enantiomeric excess in the
      recovered substrate was further confirmed by circular dichroism (CD) studies. The
      CD spectrum has a peak at 292nm and a trough at 270nm. The enantiomeric excess in
      the recovered substrate indicates that the hydroxylation at C-4 position is
      stereoselective. The significance of these results with respect to pulegone
      mediated hepatotoxicity is discussed.

PMID- 12237101
TI  - Peroxisome proliferator-activated receptor ligands negatively regulate the
      expression of the high-affinity IgE receptor Fc epsilon RI in human basophilic
      KU812 cells.
AB  - The high-affinity IgE receptor Fc epsilon RI is expressed on the cell surface of
      mast cells and basophils, and plays a central role in IgE-mediated inflammatory
      reactions. Recently, peroxisome proliferator-activated receptors (PPARs) have
      been implicated in the anti-inflammatory response. To investigate a possible role
      for PPAR in human basophils, the effect of PPAR ligands on Fc epsilon RI
      expression in human basophilic KU812 cells was studied. The PPARalpha ligand,
      leukotriene B(4), did not affect the cell surface expression of Fc epsilon RI.
      However, prostaglandin (PG) A(1) and 15-deoxy-Delta(12,14) PGJ(2) (15d-PGJ(2)),
      which are PPARbeta and gamma ligands, respectively, were both able to decrease Fc
      epsilon RI expression. Treatment with PGA(1) or 15d-PGJ(2) separately also
      reduced histamine release from KU812 cells in response to cross-linkage of Fc
      epsilon RI. In addition, RT-PCR analysis showed that KU812 cells expressed the
      mRNA for PPARalpha, beta, and gamma, indicating that PPARbeta or gamma may
      negatively regulate the cell activation via Fc epsilon RI. Cells treated with 15d
      PGJ(2) expressed lower levels of Fc epsilon RI alpha and gamma mRNA, and PGA(1)
      treatment decreased the level of Fc epsilon RI gamma mRNA. These results suggest
      that the suppression of Fc epsilon RI expression by PPARs may be due to the down
      regulation of Fc epsilon RI alpha or gamma mRNA.

PMID- 12237103
TI  - Thiol-bearing synthetic peptides retain the antioxidant activity of
      apolipoproteinA-I(Milano).
AB  - Apolipoprotein(apo)A-I(Milano) (R173C) and apoA-I(Paris) (R151C) are rare
      cysteine variants of wild-type (WT) apoA-I that possess novel antioxidant
      properties on phospholipid surfaces. Yet, the two variants differ in their
      ability to inhibit lipid peroxidation. In this study, we used synthetic peptides
      (18mers) to investigate the structural basis for the difference in antioxidant
      activity between apoA-I(Milano) and apoA-I(Paris). A peptide (aa 167-R173C-184)
      based on the amphipathic alpha helix harboring the R173C mutation inhibited
      superoxide anion-mediated oxidation of phospholipid in a dose-dependent manner,
      but it failed to directly quench superoxide anions in aqueous solution,
      indicating that the peptide acted at the level of phospholipid to inhibit lipid
      peroxidation just like the full-length cysteine variant. Peptide 145-R151C-162
      based on the helical segment containing R151C exhibited the same capacity as
      peptide 167-R173C-184 to inhibit lipid peroxidation. Thus, the difference in
      antioxidant activity between apoA-I(Milano) and apoA-I(Paris) was not governed by
      the primary amino acid sequence of their individual amphipathic alpha helices,
      rather contextual constraints within the full-length variants set the difference
      in antioxidant activity. Cysteine-free peptides were weak inhibitors of lipid
      peroxidation. These results suggest that thiol-bearing helical peptides based on
      apoA-I(Milano) may be useful to combat inflammatory related diseases.

PMID- 12237104
TI  - Two verprolin homology domains increase the Arp2/3 complex-mediated actin
      polymerization activities of N-WASP and WAVE1 C-terminal regions.
AB  - WASP family proteins induce actin polymerization through a C-terminal verprolin
      homology, cofilin homology, and acidic (VCA) region by activating the Arp2/3
      complex. The N-WASP VCA region is the most potent activator of the Arp2/3
      complex. In addition, full-length WAVE1 and a WAVE1 VCA fragment show
      differential activity. The mechanisms underlying these differences are poorly
      understood. We examined the activities of various N-WASP and WAVE1 VCA mutant
      proteins with several types of fusion moieties. When fused to GST, maltose
      binding protein, or the WAVE1 proline-rich domain, N-WASP VCA and WAVE1 VCA
      mutant proteins with two V motifs showed stronger activities than wild-type WAVE1
      VCA with one V motif, demonstrating the importance of two V motifs for strong VCA
      activity. A WAVE1 VCA fragment tagged with six histidines (His) showed markedly
      reduced activity compared to GST-fused VCA, whereas His-tagged N-WASP VCA showed
      similar activity to GST-fused VCA. An additional V motif failed to enhance WAVE1
      VCA activity in the His-tagged form. Thus, the WAVE1 VCA fragment may exist in an
      unfavorable conformation to activate the Arp2/3 complex, implying the existence
      of a structural difference between WAVE1 and N-WASP VCAs in addition to the
      number of V motifs.

PMID- 12237105
TI  - Visible region MCD and MLD spectra of nitrosylferrohemoglobin and oxyhemoglobin.
AB  - Magnetic circular dichroism (MCD) and magnetic linear dichroism (MLD)
      spectroscopies at various applied magnetic fields (0-6T) and temperatures (2.0
      31K) have been used to investigate the electronic properties of the visible (Q(0
      0), or alpha band) region of oxy- and nitrosylferrohemoglobin (HbNO). OxyHb, a
      d(6) (S=0) diamagnet, exhibits the expected pseudo-first derivative MCD and
      pseudo-second derivative MLD temperature-independent features centered at 574nm.
      HbNO, a d(7) (S=1/2) paramagnet, also exhibits a temperature-independent pseudo
      first derivative MCD spectrum, but centered at 571nm. So far as we are aware,
      this behavior is unprecedented in the MCD spectra of paramagetic iron-porphyrins,
      which are expected to be dominated by temperature-dependent C(0) terms. The HbNO
      MCD spectrum does, however, demonstrate limited field-dependent saturation
      magnetization behavior and the MLD spectrum is currently below the detection
      limit. In addition, an MCD signal from reoxygenated venous blood is reported and
      compared with MCD signals from oxy- and HbNO derivatives. Finally, a combination
      of MCD and MLD spectroscopies has been used to estimate the orbital angular
      momentum (M(L)) value of the alpha band excited state of oxyHb as 4.2 (+/-0.7).

PMID- 12237106
TI  - Continuous heat shock enhances translational initiation directed by internal
      ribosomal entry site.
AB  - Many cellular mRNAs contain internal ribosomal entry sites (IRES) that become
      functional under conditions of cellular stress, when the rate of protein
      synthesis for most cellular mRNA is reduced. Internal ribosomal entry increases
      in response to hypoxia, cell differentiation, apoptosis, gamma irradiation, and
      heat shock. Heat shock is the principal cellular stress in which general cap
      dependent translation is inhibited. On the other hand, heat shock induces the
      preferential translation of a small class of mRNA, called heat shock protein
      (HSP) mRNAs, which probably occurs because little or no eIF4F activity is
      required for their translation. In this study, we found that continuous heat
      stress enhances expression of the heat shock protein BiP at the level of
      translation. Interestingly, heat stress also enhanced the viral IRES-dependent
      translation of encephalomyocarditis virus and hepatitis C virus but not
      poliovirus. Although several BiP inducers increased BiP protein expression, BiP
      IRES-dependent translation was enhanced only during heat shock, suggesting that
      heat shock is a specific inducer for BiP IRES-dependent translation. Taken
      together, these results indicate that the mechanism of IRES-dependent translation
      can be used during heat shock and suggest that this translational mechanism may
      be critical to the survival and proliferation of cells under stress.

PMID- 12237107
TI  - A novel beta-diketone-cleaving enzyme from Acinetobacter johnsonii: acetylacetone
      2,3-oxygenase.
AB  - A novel Fe+Zn containing oxygenase from Acinetobacter johnsonii catalyses 2,3
      cleavage of acetylacetone to acetate and methylglyoxal has been purified. The
      stoichiometry of reactants and products conforms to a classical dioxygenase. The
      pure protein is a homotetramer of 64kD with variable amounts of Fe(2+) and
      Zn(2+). Activity of the enzyme is more closely related to the Fe(2+) content than
      to the amount of protein. A purification of acetylacetone 2,3-oxygenase, some of
      its physical properties, and the preference for some analogous substrates are
      described.

PMID- 12237108
TI  - Malignant reversion of a human osteosarcoma cell line, Saos-2, by inhibition of
      NFkappaB.
AB  - Beyond a pivotal role in neoplastic transformation and malignant progression,
      NFkappaB is intricately involved in bone biology, pointed up by the osteopetrotic
      phenotype of NFkappaB (p50-p52) double knock-out mice. Osteopetrosis results from
      intrinsic defects in osteoclastogenesis, loss of osteoclast bone resorptive
      activity and, questionably, increased osteoblast activity (bone matrix apposition
      and mineralization). We here report that inhibition of NFkappaB signaling
      activity in Saos-2 cells results in a marked decrease in cellular proliferation,
      assessed by the incorporation of radioactive thymidine into cellular DNA.
      Decreased cellular proliferation was accompanied by the induction of bone
      morphogenic proteins (BMP) 4, 7, and the osteoblast specific transciption factor,
      Cbfa1, heralding osteoblast differentiation, given the induction of alkaline
      phosphatase, osteopontin, and osteocalcin message levels and the attendant
      increase in matrix deposition and mineralization in vitro. These results point to
      the negative regulation of osteoblast differentiation by NFkappaB, with
      implications in the pathogenesis and progression of osteosarcomas.

PMID- 12237109
TI  - Isolation and characterization of Sphingomonas sp. GTIN11 capable of carbazole
      metabolism in petroleum.
AB  - A bacterial culture was isolated from a manufactured gas plant (MGP) soil based
      on its ability to metabolize the nitrogen-containing heterocycle carbazole. The
      culture was identified as a Sphingomonas sp. and was given the designation
      GTIN11. A cloned 4.2kb DNA fragment was confirmed to contain genes responsible
      for carbazole degradation. DNA sequence analysis revealed that the fragment
      contained five open reading frames (ORFs) with the deduced amino acid sequence
      showing homology to; carbazole terminal dioxygenase (ORF1), 2,3-dihydroxybiphenyl
      dioxygenase subunits (ORF2 and ORF3), meta-cleavage compound hydrolases (ORF4),
      and ferrodoxin component of bacterial multicomponent dioxygenases (ORF5). The
      percent similarity was 61% of these proteins or less to known proteins. The
      specific activity of Sphingomonas sp. GTIN11 for the degradation of carbazole at
      37 degrees C was determined to be 8.0 micromol carbazole degraded/min/g dry cell.
      This strain is unique in expressing the carbazole degradation trait
      constitutively. Resting cells of Sphingomonas sp. GTIN11 removed 95% of carbazole
      and 50% of C1-carbazoles from petroleum in a 16-h treatment time.

PMID- 12237110
TI  - Serum increases CYP1A1 induction by 3-methylcholanthrene.
AB  - CYP1A1 is largely involved in carcinogenesis through the bioactivation of
      numerous procarcinogens. Exposure to environmental pollutants such as polycyclic
      aromatic hydrocarbons (PAHs) leads to induction of CYP1A1 via AhR pathway. We
      have previously demonstrated that fetal bovine serum (FBS) induces CYP1A1 gene
      transcription. In this work, we show evidence that the serum does not contain an
      AhR ligand and we evaluated the effect of a 3-methylcholanthrene (3-MC) and FBS
      cotreatment on CYP1A1 expression. CYP1A1 activity was potentiated by this
      treatment. This potentiation was at least in part associated with an increase of
      the CYP1A1 mRNA and gene transcription levels. FBS potentiation of CYP1A1 PAH
      mediated induction was related to a significant increase of single strand breaks
      of DNA as compared to a single 3-MC treatment. Moreover, we demonstrated that
      human serum induces CYP1A1 with a high interindividual variability. The
      potentiation by serum of polycyclic aromatic hydrocarbon CYP1A1 induction could
      be involved in the etiology of some human cancers.

PMID- 12237111
TI  - TGF-beta1 and HGF coordinately facilitate collagen turnover in subepithelial
      mesenchyme.
AB  - We have employed co-culture of proximal tubular epithelial cells (PTEC) and renal
      tubulo-interstitial fibroblasts (TFB) to study the role of transforming growth
      factor-beta1 (TGF-beta1) and hepatocyte growth factor (HGF) in epithelial
      mesenchymal interactions. In co-culture, TGF-beta1 stimulated TFB to produce type
      I collagen (COLI). This effect was both direct and indirect, via connective
      tissue growth factor (CTGF) produced by the co-cultured PTEC. Co-administration
      of TGF-beta1 and HGF significantly increased overall COLI production by TFB by
      24h. However, in detail, this co-administration enhanced CTGF induction in PTEC
      during the first 8h, and then decreased its expression, resulting in a rapid
      decrease in expression of the alpha1(I) procollagen gene in TFB by 24h.
      Additionally, tissue inhibitor of metalloproteinase-1 was induced in PTEC by TGF
      beta1 with or without co-administration of HGF, which contributed to the COLI
      accumulation. In contrast, HGF alone or co-administered with TGF-beta1
      significantly increased collagenolytic activity derived from PTEC. Therefore, TGF
      beta1 and HGF seem to coordinately modulate epithelial-mesenchymal interactions
      to facilitate COLI turnover in subepithelial mesenchyme.

PMID- 12237112
TI  - Phosphoinositide 3-kinase C2alpha is activated upon smooth muscle cell migration
      and regulated by alpha(v)beta(3) integrin engagement.
AB  - The involvement of phosphoinositide 3-kinase C2alpha in vascular smooth muscle
      cell migration was investigated. Products of phosphoinositide 3-kinase,
      phosphatidylinositol-3-phosphate, and phosphatidylinositol-3,4-bis-phosphate were
      increased upon smooth muscle cell migration but their synthesis was affected only
      partially by phosphoinositide 3-kinase inhibitors, wortmannin and LY-294002.
      Using specific antibody, we showed that the wortmannin/LY-294002 poorly sensitive
      phosphoinositide 3-kinase C2alpha is expressed in smooth muscle cells.
      Measurement of phosphoinositide 3-kinase C2alpha activity in vitro, after
      immunoprecipitation, clearly demonstrated its activation upon smooth muscle cell
      migration. Moreover, for the first time, phosphoinositide 3-kinase C2alpha was
      found to be differentially regulated by alpha(v)beta(3) and alpha(v)beta(5)
      integrin engagement. Finally, we have identified two new potential
      phosphoinositide 3-kinase C2alpha-binding proteins, p70 and p110, which both may
      be tyrosine phosphorylated. Thus, phosphoinositide 3-kinase C2alpha might
      represent a new regulatory pathway of cell migration downstream of integrin
      engagement.

PMID- 12237113
TI  - A method to detect major serotypes of foot-and-mouth disease virus.
AB  - Nucleic acid sequence-based amplification (NASBA) is an isothermal technique that
      allows the rapid amplification of specific regions of nucleic acid obtained from
      a diverse range of sources. It is especially suitable for amplifying RNA
      sequences. A rapid and specific NASBA technique was developed, allowing the
      detection of foot-and-mouth disease virus genetic material in a range of sample
      material, including preserved skin biopsy material from infected animals,
      vaccines prepared from denatured cell-free material, and cell-free antigen-based
      detection kits. A single pair of DNA oligonucleotide primers was able to amplify
      examples of all major FMD virus subtypes. The amplified viral RNA was detected by
      electrochemiluminescence. The method was at least as sensitive as existing cell
      free antigen detection methods.

PMID- 12237114
TI  - Characteristics of the end-joining of DNA double-strand breaks by the ataxia
      telangiectasia nuclear extract.
AB  - A double-strand break was introduced in plasmid pZErO-2 at a specific site within
      the ccdB gene that is lethal to Escherichia coli cells and treated with nuclear
      extracts from human cells. The efficiency of rejoining was monitored by Southern
      blot analysis and the fidelity of rejoining was measured by expressing the ccdB
      gene after bacterial transformation. The efficiency of rejoining in the nuclear
      extract from an ataxia-telangiectasia (A-T) cell line was comparable to that from
      a control cell line. However, the accuracy of rejoining was much lower for the A
      T cell extract than for the control cell extract. All mutations were deletions,
      most of which contained short direct repeats at the breakpoint junctions. The
      deletion spectrum caused by the A-T nuclear extract was distinct from that of the
      control extract. These results indicate that the ccdB gene is useful for analysis
      of mis-rejoining and that A-T cells have certain deficiencies in end-joining of
      double-strand breaks in DNA.

PMID- 12237115
TI  - Enhancing oxidative resistance of Agrobacterium radiobacter N-carbamoyl D-amino
      acid amidohydrolase by engineering solvent-accessible methionine residues.
AB  - N-Carbamoyl D-amino acid amidohydrolase (D-NCAase) that catalyzes the
      stereospecific hydrolysis of N-carbamoyl D-amino acids to their corresponding D
      amino acids is valuable in pharmaceutical industry. Agrobacterium radiobacter D
      NCAase is sensitive to oxidative damage by hydrogen peroxide. To investigate the
      role of methionine residues in oxidative inactivation, each of the nine
      methionine residues in A. radiobacter D-NCAase was substituted with leucine,
      respectively, by site-directed mutagenesis. Except for two mutants (Met5Leu and
      Met31Leu) with similar activities, seven mutants (Met73Leu, Met167Leu/Met169Leu,
      Met184Leu, Met220Leu, Met239Leu, Met244Leu, and Met239Leu/Met244Leu) were found
      to have reduced activities. In the presence of H(2)O(2), three mutants
      (Met239Leu, Met244Leu, and Met239Leu/Met244Leu) with substitution of highly
      solvent-accessible methionines by leucines retained their activities. The other
      mutants were also considerably resistant to chemical oxidation than was the wild
      type enzyme. Thus, substitution of solvent-accessible methionine residues with
      leucine to enhance oxidative stability of D-NCAase is practical but might be with
      compromised activity.

PMID- 12237116
TI  - Oxidoreductive modification of two cysteine residues in paired domain by Ref-1
      regulates DNA-binding activity of Pax-8.
AB  - We have reported reversible oxidoreductive regulation of DNA-binding activity of
      Pax-8: oxidation inhibits its binding and subsequent reduction restores the
      binding. Here, we show that Cys-45 and Cys-57 in the paired domain of rat Pax-8,
      which are conserved in all Pax members, are responsible for the redox regulation
      of its binding. Electrophoretic mobility shift assay using deletion mutants and
      mutants with substitution of cysteine with serine revealed that oxidation by
      diamide of either Cys-45 or Cys-57 loses the DNA binding of Pax-8. An
      intracellular oxidoreductive enzyme redox factor-1 (Ref-1) could reduce the
      oxidized Cys-45 or Cys-57 and restored the binding. Furthermore, reporter gene
      assay showed that transcriptional activity of wild-type Pax-8 was enhanced by co
      expression of Ref-1. When the mutant with double substitutions of Cys-45 and Cys
      57, which was insensitive to oxidation, was transfected, the basal
      transactivation level was much higher than that of wild-type Pax-8, while it was
      not enhanced by Ref-1. These results demonstrated that oxidoreductive
      modification of Cys-45 and Cys-57 via Ref-1 plays a role in redox regulation of
      Pax-8 in living cells.

PMID- 12237117
TI  - Calpain is required for MMP-2 and u-PA expression in SV40 large T-antigen
      immortalized cells.
AB  - The absence of both mu- and m-calpain activity, caused by disruption of the capn4
      gene in mice, retarded migration, and disrupted the cytoskeleton, both in primary
      capn4(-/-) embryonic fibroblasts (mEF) and in capn4(-/-) mEF immortalized with
      SV40 large T-antigen (TAg). These results are thought to reflect the role of
      calpain in integrin signaling to the cytoskeleton. The integrins are also
      involved, together with matrix metalloproteinases (MMP) and plasminogen
      activators (PA), in cellular invasion. This study therefore aimed to establish
      whether links exist between the calpain, MMP, and PA systems, using both primary
      and TAg-immortalized capn4(+/+) and capn4(-/-) embryonic fibroblasts. Both
      Matrigel invasion, and expression of MMP-2 and u-PA activities, correlated with
      calpain expression in TAg-containing cells, but not in primary cells. MMP-2 mRNA
      synthesis also correlated with calpain expression in the presence of TAg, but u
      PA mRNA synthesis was not so correlated. The results suggest that calpain
      acquires new regulatory roles in the presence of TAg. Calpain is also required
      for v-Src-mediated transformation. It appears that calpain may have previously
      unsuspected roles in oncogenic transformation.

PMID- 12237118
TI  - Comparison of Na(+)/Ca(2+) exchanger current and of its response to isoproterenol
      between acutely isolated and short-term cultured adult ventricular myocytes.
AB  - The Na(+)/Ca(2+) exchanger protein is present in the cell membrane of many tissue
      types and plays key roles in Ca(2+) homeostasis, excitation-contraction coupling,
      and generation of electrical activity in the heart. The use of adult ventricular
      myocyte cell culture is important to molecular biological approaches to study the
      roles and modulation of the cardiac Na(+)/Ca(2+) exchanger. Therefore, we
      characterised the functional expression of the exchanger in adult guinea-pig
      ventricular myocytes maintained in short-term culture (for 4 days) and compared
      the response of ionic current (I(NaCa)) carried by the exchanger from acutely
      isolated and Day 4 cells to beta-adrenoceptor activation with isoproterenol
      (ISO). Functional activity of the exchanger was assessed by measuring I(NaCa)
      using whole cell patch clamp, under selective recording conditions. I(NaCa)
      amplitude measured at both +60 and -100mV declined significantly by Day 1 of cell
      culture, showing a further small decline by Day 4. However, cell surface area
      (assessed by measuring membrane capacitance) also declined over this time-frame.
      I(NaCa) normalised to membrane capacitance (I(NaCa) density) did not differ
      significantly between acutely isolated and cells cultured for 4 days. However,
      although ISO (1 microM) increased I(NaCa) in acutely isolated myocytes, it
      exerted no significant effect on I(NaCa) from Day 4 cells. This was not due to an
      inherent inability of these cells to respond to ISO, as L-type calcium current
      amplitude from Day 4 cells was increased by ISO to a similar extent as that from
      acutely isolated cells. Our data suggest that the functional expression of the
      Na/Ca exchanger is well maintained during short-term culture of adult ventricular
      myocytes. The lack of response to ISO of I(NaCa) from Day 4 cells suggests: (a)
      that, despite a well-maintained I(NaCa) density, cultured adult myocytes may not
      necessarily be suitable for studies of exchanger modulation by some agonists and
      (b) that there may exist subtle differences between beta-adrenergic regulation of
      the exchanger protein and of L-type Ca channels.

PMID- 12237119
TI  - C-terminal lysine truncation increases thermostability and enhances chaperone
      like function of porcine alphaB-crystallin.
AB  - The carboxyl-terminal segment of alpha-crystallin, a major lens protein of all
      vertebrates, has a short and flexible peptide extension of about 20 amino acid
      residues that are very susceptible to proteolytic truncation and modifications
      under physiological conditions. To investigate its role in crystallin aggregation
      and chaperone-like activity, we constructed a mutant of porcine alphaB-crystallin
      with C-terminal lysine truncated end, which unexpectedly showed better chaperone
      like function than wild-type alphaB-crystallin. From circular dichroism (CD)
      spectra, we show that the mutant possesses similar secondary and tertiary
      structures to those of native purified and recombinant alphaB-crystallins.
      Analytical ultracentrifugation revealed that the truncated mutant was smaller
      than wild-type alphaB-crystallin in aggregation size and mass. The observed
      higher thermostability and anti-thermal aggregation propensity of the truncated
      alphaB-crystallin mutant than wild-type alphaB-crystallin are in contrast to the
      prevailing notion that mutations at the C-terminal lysines of alphaB-crystallin
      result in substantial loss of chaperone-like activity, despite the overall
      preservation of secondary structure. The detailed characterization of the C
      terminal deletion mutants may provide some deeper insight into the chaperoning
      mechanism of the structurally related small heat-shock protein family.

PMID- 12237120
TI  - Overexpressed chloride intracellular channel protein CLIC4 (p64H1) is an
      essential component of novel plasma membrane anion channels.
AB  - Chloride intracellular channel protein CLIC4 is a putative organellar anion
      channel or channel regulator with an unusual dual cytoplasmic and integral
      membrane localisation. To investigate its contribution to cellular anion channel
      activity, the protein was overexpressed in stably transfected HEK-293 cells.
      Patch-clamp recording revealed CLIC4-associated indanyloxyacetic acid-sensitive
      (IC(50) approximately 100 microM) plasma membrane currents showing mild outward
      rectification, and novel low conductance (approximately 1pS) CLIC4-associated
      anion channels were resolved at the single-channel level. The CLIC4-associated
      channels were inhibited by anti-CLIC4 antibodies, including a monoclonal antibody
      directed against a FLAG epitope fused to the C-terminus of CLIC4, but only when
      these were applied to the cytoplasmic (not the external) face of the membrane.
      CLIC4 is thus an essential molecular component of novel cellular anion channels
      and the C-terminus of the integral membrane form of CLIC4 is cytoplasmic.

PMID- 12237121
TI  - IF3, a novel cell-differentiation factor, highly expressed in murine liver and
      ovary.
AB  - The IF3 gene was isolated by expression cloning from a cDNA library of mouse
      oocytes. This gene was revealed to have no homology to any known gene and its
      cDNA encodes a 202-amino acid protein that contains a signal-peptide sequence.
      Moreover, an IF3 isoform, IF3(2), was expressed in both liver and ovary. Its cDNA
      encoded a 92-amino acid protein contains a signal-peptide sequence, which may be
      an alternative splice and frameshift form of IF3. The mRNA of IF3s was expressed
      in oocytes, ovary, and liver. Moreover, the gene expression of IF3s was regulated
      in a development-dependent manner in preimplantation-embryo and liver. Both
      IF3(1) and IF3(2) isoforms induced the differentiation of 2T3 and ATDC5 cells to
      the osteogenic and chondrogenic phenotype, respectively, suggesting that IF3s may
      modulate the differentiation status. Our findings suggest that IF3 may be one of
      the secreted factors that regulate oogenesis and certain liver functions.

PMID- 12237122
TI  - IL-15 up-regulates iNOS expression and NO production by gingival epithelial
      cells.
AB  - To investigate the biological activity of epithelial cells in view of host
      defense, we analyzed the mRNA expression of inducible NOS (iNOS) as well as NO
      production by human gingival epithelial cells (HGEC) stimulated with IL-15. RT
      PCR analysis revealed that HGEC expressed IL-15 receptor alpha-chain mRNA. In
      addition, stimulation with IL-15 enhanced iNOS expression by HGEC through an
      increase of both mRNA and protein levels. Moreover, IL-15 up-regulated the
      production of NO(2)(-)/NO(3)(-), a NO-derived stable end product, from HGEC. The
      enhanced NO production by IL-15 was inhibited by AMT, an iNOS-specific inhibitor.
      These results suggest that IL-15 is a potent regulator of iNOS expression by HGEC
      and involved in innate immunity in the mucosal epithelium.

PMID- 12237123
TI  - Rat parietal cells express CCK(2) receptor mRNA: gene expression analysis of
      single cells isolated by laser-assisted microdissection.
AB  - Gastrin plays a crucial role in maintaining a normal cellular composition and
      function of the oxyntic mucosa. It has been debated for decades whether parietal
      cells possess cholecystokinin-2 (CCK(2)) receptors and interact directly with
      gastrin. We investigated whether parietal cells express CCK(2) receptor mRNA by
      using new molecular biology techniques. Rat oxyntic mucosal cells were dispersed
      and enriched by elutriation, and single parietal and ECL cells were isolated from
      cell smears by means of laser microbeam microdissection and laser pressure
      catapulting. The mRNA from each single cell was isolated and subjected to one
      step multiplex or conventional reverse transcription-polymerase chain reaction
      and subsequent nested PCR. Specific primers for the CCK(2) receptor were used in
      combination with primers for H,K-ATPase and histidine decarboxylase, specific
      markers for parietal and ECL cells, respectively. CCK(2) receptor mRNA was
      detected in 25% of the rat parietal cells and 40% of the ECL cells examined.

PMID- 12237124
TI  - The specific mitochondrial DNA polymorphism found in Klinefelter's syndrome.
AB  - Hypervariable segments of mitochondrial DNA (mtDNA) (HV1 and HV2) were analyzed
      in Klinefelter's syndrome and compared to normal population data. One pair of
      samples consisting of a Japanese mother and affected son with Klinefelter's
      syndrome (involved in a criminal case), and seven unrelated DNA samples from
      Caucasian Klinefelter males (two involved in criminal cases and five diagnosed)
      were collected in Japan and the United States. The diagnosis of Klinefelter's
      syndrome was established previously by multiplex XY-STR typing detecting two X
      alleles and one Y allele in the samples. Haplotype analysis of the mtDNA sequence
      in Klinefelter males was found to be identical, unique, and specific, as it was
      not found in the normal population. Astonishingly, family data exhibited that the
      haplotype of the mtDNA in the son was apparently different from the mother's,
      suggesting that the mtDNA of Klinefelter male would not be inherited from mother
      to son. Our data indicate that possible interaction of the sex chromosome and the
      mtDNA exists, and suggests that the specific mtDNA haplotype could cause the
      abnormal cell to fertilize and reproduce itself.

PMID- 12237125
TI  - Hypoxic induction of hypoxia-inducible factor-1alpha and oxygen-regulated gene
      expression in mitochondrial DNA-depleted HeLa cells.
AB  - Hypoxia increases the accumulation of hypoxia-inducible factor-1alpha (HIF
      1alpha) and induces transcription of a variety of genes including vascular
      endothelial growth factor (VEGF) gene through oxygen sensing mechanisms. In one
      model, mitochondria-derived reactive oxygen species (ROS) are suggested to be
      involved in oxygen sensing. Here, we found that hypoxia increased ROS generation
      and VEGF gene expression in HeLa cells. To further investigate the role of ROS in
      oxygen sensing, we compared the hypoxic response between rho(0) HeLa cells
      lacking mitochondrial DNA (EB8) and rho(0) HeLa cells containing mitochondrial
      DNA from wild-type HeLa cells (HeEB1). The results showed that, although hypoxia
      markedly increased ROS generation in HeEB1 cells but not in EB8 cells, EB8 cells
      showed essentially a normal response to hypoxia, as assessed by VEGF gene
      promoter activity, HIF-1alpha accumulation, and HIF-1 target gene expressions.
      These results indicate that mitochondria-derived ROS generated in response to
      hypoxia are not necessary for oxygen sensing in HeLa cells.

PMID- 12237126
TI  - Tyrosine phosphorylation of clathrin heavy chain under oxidative stress.
AB  - In mouse pancreatic insulin-producing betaTC cells, oxidative stress due to
      H(2)O(2) causes tyrosine phosphorylation in various proteins. To identify
      proteins bearing phosphotyrosine under stress, the proteins were affinity
      purified using an anti-phosphotyrosine antibody-conjugated agarose column. A
      protein of 180kDa was identified as clathrin heavy chain (CHC) by electrophoresis
      and mass spectrometry. Immunoprecipitated CHC showed tyrosine phosphorylation
      upon H(2)O(2) treatment and the phosphorylation was suppressed by the Src kinase
      inhibitor, PP2. The phosphorylation status of CHC affected the intracellular
      localization of CHC and the clathrin-dependent endocytosis of transferrin under
      oxidative stress. In conclusion, CHC is a protein that is phosphorylated at
      tyrosine by H(2)O(2) and this phosphorylation status is implicated in the
      intracellular localization and functions of CHC under oxidative stress. The
      present study demonstrates that oxidative stress affects intracellular vesicular
      trafficking via the alteration of clathrin-dependent vesicular trafficking.

PMID- 12237127
TI  - Antimicrobial peptide defenses of the Tarahumara frog, Rana tarahumarae.
AB  - Populations of the Tarahumara frog Rana tarahumarae have decreased markedly in
      recent years in the northern part of their range. Infection by the chytrid fungus
      Batrachochytrium dendrobatidis has been implicated in these declines. To
      determine whether antimicrobial peptides in the skin provide protection against
      this pathogen, norepinephrine-stimulated skin secretions were tested for their
      ability to inhibit growth of B. dendrobatidis in vitro. After concentration,
      crude mixtures of skin peptides inhibited the growth of the chytrid in a
      concentration-dependent manner. Proteomic analysis led to the identification and
      characterization of three peptides belonging to the brevinin-1 family of
      antimicrobial peptides and three belonging to the ranatuerin-2 family. The two
      most abundant peptides, ranatuerin-2TRa (GIMDSIKGAAKEIAGHLLDNLKCKITGC) and
      brevinin-1TRa (FLPVIAGIAANVLPKLFCKLTKRC), were active against B. dendrobatidis
      (MIC of 50 microM for ranatuerin-2TRa and 12.5 microM for brevinin-1TRa against
      zoospores). These data clearly show that antimicrobial peptides in the skin
      secretions of the Tarahumara frog are active against B. dendrobatidis and should
      provide some protection against infection. Therefore, the observed susceptibility
      of these frogs to this pathogen in the wild may be due to the effects of
      additional environmental factors that impair this innate defense mechanism,
      leading to the observed population declines.

PMID- 12237128
TI  - Functional analysis and the molecular dissection of zinc-fingers and homeoboxes 1
      (ZHX1).
AB  - Zinc-fingers and homeoboxes 1 (ZHX1) is a protein that interacts with the
      activation domain of the A subunit of nuclear factor-Y. The function of ZHX1, as
      a transcription factor, was characterized and their domains were mapped. To
      determine the nuclear localization signal, expression vectors, in which various
      truncated forms of ZHX1 were fused to the C-terminal of green fluorescence
      protein (GFP), were transfected into human embryonic kidney (HEK) 293 cells. All
      GFP-ZHX1 fusion proteins including an arginine-rich region that corresponds to
      the amino acid sequence between 734 and 768 were localized in the nuclei. A
      dimerization domain of the ZHX1 was also mapped using protein-protein interaction
      assays. The homeodomain (HD) 1 consisting of the amino acid sequence between 272
      and 432 of ZHX1 was necessary and sufficient for dimerization. Lastly, the
      transcriptional activity of ZHX1 was examined using a mammalian one-hybrid
      system. ZHX1, fused to the C-terminal of the GAL4 DNA-binding domain, was co
      transfected with luciferase reporter plasmids with or without five copies of the
      GAL4-binding site into HEK293 cells. The luciferase activity was decreased in
      both concentration- and GAL4-binding site-dependent manner. The acidic region
      corresponding to the amino acid sequence between 831 and 873 was a repressor
      domain and dimerization was prerequisited for full repressor activity.

PMID- 12237129
TI  - A role of heparin-binding epidermal growth factor-like growth factor in cardiac
      remodeling after myocardial infarction.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is known to
      induce cell growth in various cell types via transactivation of epidermal growth
      factor receptor (EGFR). To investigate the involvement of HB-EGF and EGFR in
      cardiac remodeling after myocardial infarction (MI), we examined the expressions
      of mRNA and protein in rat hearts 6 weeks after MI-induction. Where increased
      expressions of HB-EGF mRNA and protein were observed, infarcted myocardium was
      replaced by extracellular matrix and interstitial fibroblasts. EGFR mRNA and
      protein expression did not show significant changes in sham-operated heart
      tissues, non-infarcted region, and infarcted region. In vitro study demonstrated
      that HB-EGF mRNA was expressed mainly in cultured fibroblasts rather than in
      myocytes. We suggest that the interaction between HB-EGF and EGFR transactivation
      is closely related to the proliferation of cardiac fibroblasts and cardiac
      remodeling after MI in an autocrine, paracrine, and juxtacrine manner.

PMID- 12237131
TI  - Glycine 38 is crucial for the ribonucleolytic activity of human pancreatic
      ribonuclease on double-stranded RNA.
AB  - Human pancreatic ribonuclease (HPR) and bovine seminal ribonuclease (BS-RNase)
      exhibit significantly higher activity against double stranded RNA (dsRNA),
      compared to RNase A. The high dsRNA cleavage activity of BS-RNase, in part, has
      been attributed to glycine residues at positions 38 and 111. HPR possesses a
      glycine residue at position 38, whereas it has a glutamic acid at position 111.
      To understand the mechanism of dsRNA degradation by the single strand preferring
      HPR, we have generated HPR variants containing mutations at positions 38 and 111.
      Our study shows that Glycine 38 is crucial for the full catalytic activity of the
      human enzyme on duplex RNA as its substitution with aspartate or alanine results
      in a drastic reduction in the dsRNA cleavage activity of HPR. The substitution of
      Glutamate111 with glycine also resulted in the reduction of the dsRNA cleavage
      activity of HPR, indicating that a glycine residue at 111 is not a requirement
      for the ribonucleolytic activity on double stranded substrate.

PMID- 12237130
TI  - Enzymatic synthesis and characterization of oligosaccharides structurally related
      to the repeating unit of Pullulan.
AB  - A trisaccharide (Glcalpha1-4Glcalpha1-6Glc) and a tetrasaccharide (Glcalpha1
      4Glcalpha1-4Glcalpha1-6Glc) the structures of which are related to that of
      repeating unit of pullulan have been obtained, exploiting the transglycolytic
      activity of Aspergillus niger cyclodextrin glucanotransferase. Both products were
      obtained in one-pot reaction using as a donor the alpha-cyclodextrin and as an
      acceptor the disaccharide isomaltose. The regioselectivity of the reaction was
      85% for the tetrasaccharide and 80% for the trisaccharide. The yield of reaction
      resulted to be 42% for the synthesis of trisaccharide and 25% for that of
      tetrasaccharide. Purification of products was performed by size exclusion
      chromatography and by semipreparative reverse phase HPLC after reversible
      derivatization with 2-aminopyridine. Structural characterization was performed by
      capillary electrophoresis, ion-spray mass spectrometry, and by 13C-NMR
      spectroscopy. A comparison of these results with those obtained by using alpha-D
      glucosidase, which had been effective for the synthesis of the disaccharide
      isomaltose, is reported.

PMID- 12237132
TI  - Single replication origin of the archaeon Methanosarcina mazei revealed by the Z
      curve method.
AB  - The genomic sequence of the archaeon Methanosarcina mazei has been analyzed by
      the Z curve method. The Z curve is a three-dimensional curve that uniquely
      represents the given DNA sequence. The three-dimensional Z curve and its x and y
      components for the genome of M. mazei show a sharp peak and relatively broad
      peak, respectively. The cdc6 gene is located exactly at the position of the sharp
      peak. Based on the known behavior of the Z curves for the archaea whose
      replication origins have been identified, we hypothesize that the replication
      origin and termination sites correspond to the positions of the sharp peak and
      broad peak, respectively. We have located an intergenic region that is between
      the cdc6 gene (MM1314) and the gene for an adjacent protein (MM1315), which shows
      strong characteristics of the known replication origins. This region is highly
      rich in AT and contains multiple copies of consecutive repeats. Our results
      strongly suggest that the single replication origin of M. mazei is situated at
      the intergenic region between the cdc6 gene and the gene for the adjacent
      protein, from 1,564,657 to 1,566,241 bp of the genome.

PMID- 12237133
TI  - Comparative phenotypic analyses of human plasma and urinary retinol binding
      protein using mass spectrometric immunoassay.
AB  - Mass spectrometric immunoassay (MSIA) is a proteomics technology that combines
      the selectivity of affinity capture with the sensitivity and resolution of mass
      spectrometric detection. This unique approach allows for intact protein
      identification therefore is readily capable of discriminating between protein
      variants, i.e., mutations, posttranslational modifications, and truncations. In
      this work, MSIA is used in the comparative analyses of retinol binding protein
      (RBP) from the plasma and urine of a small study population. Detailed RBP
      profiles were obtained from both biological fluids, resulting in the
      identification of several catabolic RBP products (present in urine) that have not
      been previously reported. In addition, comparative analysis of urine samples
      taken from healthy and renally impaired individuals revealed different breakdown
      profiles. These results illustrate the use of MSIA for the rapid, sensitive, and
      accurate profiling of RBP both within and between individuals.

PMID- 12237134
TI  - Spectrophotometric investigations with hexa-coordinate ferric lignin peroxidase:
      does water retention at the active site influence catalysis?
AB  - Native lignin peroxidase (LIP) can adopt either a stable penta- or hexa
      coordinate state. We have examined catalysis with hexa-coordinate ferric LIP as
      the starting material, using rapid scanning spectrophotometry. Initial two
      electron oxidation of hexa-coordinate native LIP by H(2)O(2) (Compound I
      formation) was accompanied by a shifting isosbestic point (419-->416 nm),
      consistent with displacement of a resident water molecule, prior to the reaction
      of the ferric iron with H(2)O(2). The Compound I species derived from a hexa
      coordinate ferric state shows an unusual peak at 520 nm, which may be due to
      water retention in the vicinity of the heme active site. Compound I reduction by
      veratryl alcohol showed saturation kinetics, which contrasts with the situation
      observed when Compound I is derived from a penta-coordinate ferric state. The
      data inferred that water can interfere with heme access by electron donors,
      altering the mechanism of Compound I reduction.

PMID- 12237135
TI  - Elevation of P-glycoprotein function by a catechin in green tea.
AB  - The ABC transporter P-glycoprotein (P-gp) exerts a critical role in the systemic
      disposition of and exposure to lipophilic and amphipathic drugs, carcinogens,
      toxins, and other xenobiotics. The ability of P-gp to transfer a wide variety of
      structurally unrelated compounds from the cell interior across the membrane
      bilayer remains intriguing. Since dietary chemicals in green tea (and several
      other foods) appear to exert anticarcinogenic effects by an unknown mechanism,
      the constituents are frequently studied for interactions with various
      biomacromolecules as well as cytotoxins or isolated cells. We characterized
      several green tea catechins for their interaction with P-gp and their specific
      effects on P-gp export activity of several marker substrates. Some of these
      compounds inhibit the active efflux of the fluorescent markers LDS-751 (LDS) and
      rhodamine 123 (Rho) with low potency. Remarkably, others of these catechins
      facilitate the P-gp-mediated transport of LDS without affecting daunorubicin
      (DNR) transport or Rho. Moreover, (-)epicatechin, though an inhibitor of Rho
      transport, can significantly enhance the active net transport of another P-gp
      marker substrate, LDS. This result indicates that (-)epicatechin may bind to and
      activate an allosteric site that enhances P-gp overall function or efficiency.
      Such a mechanism of heterotropic allosteric enhancement of P-gp could serve as
      chemoprotective to many cells and contribute to the purported anticarcinogenic
      effect of green tea consumption.

PMID- 12237136
TI  - Incadronate disodium inhibits advanced glycation end products-induced
      angiogenesis in vitro.
AB  - We have previously shown that advanced glycation end products (AGE), senescent
      macroprotein derivatives formed at an accelerated rate in diabetes, induced
      angiogenesis through overgeneration of autocrine vascular endothelial growth
      factor (VEGF). In the present study, effects of incadronate disodium, a nitrogen
      containing bisphosphonate on AGE-elicited angiogenesis in vitro, were studied.
      Incadronate disodium was found to completely inhibit AGE-induced increase in DNA
      synthesis as well as tube formation of human microvascular endothelial cells
      (EC). Furthermore, incadronate disodium significantly prevented transcriptional
      activation of nuclear factor-kappaB and activator protein-1 and the subsequent up
      regulation of VEGF mRNA levels in AGE-exposed EC. Farnesyl pyrophosphate, but not
      geranylgeranyl pyrophosphate, was found to completely restore the anti-angiogenic
      effects of incadronate disodium on EC. These results suggest that incadronate
      disodium could block the AGE-signaling pathway in microvascular EC through
      inhibition of protein farnesylation. Incadronate disodium may be a promising
      remedy for treatment of patients with proliferative diabetic retinopathy.

PMID- 12237137
TI  - Cryptosporidium infection in dogs in Osaka, Japan.
AB  - Cryptosporidium parvum is a zoonotic pathogen composed of genetically distinct
      but morphologically identical genotypes. Recent molecular study indicates that
      dogs may transmit the cattle genotype, which is known to be pathogenic to humans.
      Although large-scale studies of Cryptosporidium infection in dogs have been
      performed in several countries, the isolates were not accurately identified
      because of the lack of a method for molecular analysis. It is important to
      identify the isolates harbored in dogs, which come in close contact with humans,
      in order to control human cryptosporidiosis. The aim of the present study was to
      calculate the prevalence of Cryptosporidium infection in dogs in Osaka city,
      Japan, and to characterize the isolates molecularly. The prevalence was
      determined to be 9.3% (13/140) by PCR. All isolates were found to be
      Cryptosporidium canis (previously known as the dog genotype), which is thought to
      be non-pathogenic in humans, based on the sequencing of diagnostic fragments.
      These results indicate that PCR-based diagnostic methods are a useful tool for
      the diagnosis and molecular epidemiology of Cryptosporidium infection in dogs,
      and that dogs living in Osaka are not a significant reservoir for human
      cryptosporidiosis. It is unclear why C. canis is dominant in dogs. Further study
      is required to understand this partial parasitism.

PMID- 12237138
TI  - Comparative studies of the efficacy of parvaquone and parvaquone-plus-frusemide
      in the treatment of Theileria parva infection (East Coast fever) in cattle.
AB  - Comparative studies of the efficacy of parvaquone (Parvexon) and parvaquone-plus
      frusemide (Fruvexon) Bimeda Chemicals, Ireland, were done on 60 naturally
      infected cases of East Coast fever (ECF; Theileria parva infection in cattle).
      Small-scale dairy farmers in the peri-urban of Dar Es Salaam city reported ECF
      suspected cases from March to mid-October 2001 and were treated with the two
      drugs alternately, as were diagnosed positive for ECF. Four sub-groups of 15
      cattle each (early stage, 15; advanced stage, 15) were treated with parvaquone
      and parvaquone-plus-frusemide. Twenty-eight out of 30 (93.3%) cattle treated with
      parvaquone-plus-frusemide were cured, so do 24 out of 30 (80.0%) cattle treated
      with parvaquone without frusemide. Early diagnosis and prompt management of
      pulmonary signs, which accounted for 30.0% of total ECF cases is advised in order
      to improve cure rates. Unlike parvaquone without frusemide (Parvexon), parvaquone
      plus-frusemide (Fruvexon) proved useful in the management of pulmonary signs,
      hence, a drug of choice in the treatment of ECF cases that are accompanied by or
      are likely to manifest pulmonary signs.

PMID- 12237139
TI  - Modulation of sheep lymphocyte responses by Fasciola hepatica excretory-secretory
      products.
AB  - The effect of Fasciola hepatica excretory-secretory products (FhESPs) on mitogen
      induced proliferation of sheep peripheral blood mononuclear cells (PBMCs) and
      PBMC subsets (CD2(+), CD4(+), CD8(+), gammadeltaTCR(+) or CD21(+) cells) were
      studied. PBMCs were incubated with Concanavalin A (ConA) or phytohemagglutinin
      (PHA) at optimal (1 microg per well) or suboptimal (0.25 microg per well) doses
      and with FhESPs at several doses (1.25-20 microg per well). PBMC subsets were
      incubated with ConA at a suboptimal dose and with FhESPs at 5 microg per well.
      These cells were incubated with or without monocytes (CD14(+) cell). FhESPs
      slightly increased the proliferation of PBMCs stimulated with optimal doses of
      PHA. FhESPs (10 and 20 microg per well) inhibited the PBMCs stimulated with
      optimal doses of ConA. FhESP dose-dependent inhibition was observed on PBMCs
      stimulated with suboptimal doses of ConA. CD21(+) lymphocytes (B lymphocytes),
      CD14(+) cells (monocytes) and gammadeltaTCR(+) cells were not stimulated by ConA.
      T lymphocyte subsets (CD2(+), CD4(+) or CD8(+) cells) proliferation was decreased
      by FhESPs at 5 microg per well. FhESPs inhibits the ConA-induced stimulation of
      sheep PBMCs and sheep T lymphocyte subsets. Further studies should be done to
      investigate the mechanism of this FhESP immunomodulatory effect.

PMID- 12237140
TI  - Improved detection of endoparasite DNA in soil sample PCR by the use of anti
      inhibitory substances.
AB  - Although there have been numerous microbial examinations of soil for the presence
      of human pathogenic developmental parasite stages of Ancylostoma caninum and
      Toxocara canis, molecular techniques (e.g. DNA extraction, purification and
      subsequent PCR) have scarcely been applied. Here, DNA preparations of soil
      samples artificially contaminated with genomic DNA or parasite eggs were examined
      by PCR. A. caninum and T. canis-specific primers based on the ITS-2 sequence were
      used for amplification. After the sheer DNA preparation a high content of PCR
      interfering substances was still detectable. Subsequently, two different
      inhibitors of PCR-interfering agents (GeneReleaser, Bioventures Inc. and
      Maximator, Connex GmbH) were compared in PCR. Both substances increased PCR
      sensitivity greatly. However, comparison of the increase in sensitivity achieved
      with the two compounds demonstrated the superiority of Maximator, which enhanced
      sensitivity to the point of permitting positive detection of a single A. caninum
      egg and three T. canis eggs in a soil sample. This degree of sensitivity could
      not be achieved with GeneReleaser for either parasite Furthermore, Maximator not
      only increased sensitivity; it also cost less, required less time and had a lower
      risk of contamination. Future applications of molecular methods in
      epidemiological examinations of soil samples are discussed/elaborated.

PMID- 12237141
TI  - Comparative use of faecal egg count reduction test, egg hatch assay and beta
      tubulin codon 200 genotyping in small strongyles (cyathostominae) before and
      after benzimidazole treatment.
AB  - A survey on benzimidazole (BZ) resistance in small strongyles was performed on
      three farms in the tenth region in Chile. Samples from a total of 100 horses were
      tested using the faecal egg count reduction test (FECRT), the egg hatch assay
      (EHA) and an allele-specific PCR for the detection of beta-tubulin isotype 1
      genes coding for phenylalanine (phe) or tyrosine (tyr) at codon 200. In the past,
      BZ-type drugs have been used within anthelmintic campaigns on all the three
      farms. This has predictably led to a high degree of BZ resistance at the Valdivia
      and Rinihue farms and to a lesser degree at the Frutillar farm, as demonstrated
      by all the three tests. The FECRT indicated resistance in every farm by faecal
      egg count reductions (FECR) of 27% (S.D. +/- 33), 26.5% (S.D. +/- 26.9) and 83.9%
      (S.D. +/- 22.8) for the Valdivia, Rinihue and Frutillar farms, respectively. With
      the EHA, the following mean LD(50) values were found before and after treatment
      with fenbendazole (FBZ): 0.093, 0.141 and 0.066 microg TBZ/ml and 0.149, 0.158
      and 0.091 microg TBZ/ml, respectively, for the Valdivia, Rinihue and Frutillar
      samples. The corresponding LD(96) values were 0.222, 0.263 and 0.188 microg
      TBZ/ml before treatment and 0.316, 0.322 and 0.221 microg TBZ/ml after treatment,
      indicating BZ resistance in all the cases. Genotyping was performed on more than
      1700 single larvae, at least 10 per faecal sample, for 98 pre- and 66 post
      treatment samples. Despite a general trend toward higher percentages of phe/tyr
      and tyr/tyr individuals following treatment, no statistically significant
      difference was found between these two and the phe/phe genotype percentages.
      However, a significantly negative correlation was detected between the LD(50)
      values and the phe/phe percentages and there was a positive correlation between
      the FECRT results and the phe/phe percentages. Thus, there seems to be a
      difference in the significance of the codon 200 polymorphism in the mechanisms of
      BZ resistance in small strongyles of the horse and sheep trichostrongyles.

PMID- 12237142
TI  - Linognathus vituli (Anoplura: Linognathidae): population growth, dispersal and
      development of humoral immune responses in nai;ve calves following induced
      infestations.
AB  - Growth of Linognathus vituli populations following establishment at a point
      source was followed for 16 weeks on eight louse-naive Holstein calves. Dispersal
      of lice from the point of infestation (withers) was monitored by examination of
      known louse predilection sights. Mean louse indices increased during the initial
      weeks reaching maximum mean values at 8 weeks post-infestation (p.i.).
      Subsequently, mean indices decreased, reaching a plateau that persisted through
      weeks 14 and 15 p.i. There was little movement away from the withers until 5
      weeks p.i. Subsequently, numbers of lice on the withers declined, while
      increasing at sites on the head. A few lice were noted on the dewlap and topline
      sites. Host antibody responses to crude nymph antigens, measured by enzyme-linked
      immunosorbent assay (ELISA), were generally evident within 2-4 weeks of
      infestation. Examination of individual host data showed louse populations could
      be categorized relative to the mean population size for the group. Two animals
      were considered 'chronic', having louse populations that persisted throughout the
      study and whose louse indices were >150% of the group mean. Two animals were
      classified as 'resistant' having lice present for only a portion of the study and
      whose louse indices <40% of the group mean. The remaining animals had louse
      indices between 62 and 137% of the group mean. Antibody profiles of the
      individuals were not as clearly categorized, although the 'resistant' animals
      were only positive for short periods of time, roughly corresponding to the time
      when lice were observed.

PMID- 12237143
TI  - Effect of nematode burden as assessed by means of faecal egg counts on body
      condition in goats farmed under resource-poor conditions in South Africa.
AB  - A longitudinal study was conducted of the nematode faecal egg counts (FECs) and
      body condition scores (BCSs) of goats of resource-poor farmers at Rust de Winter,
      Gauteng Province, Impendle, KwaZulu-Natal Province, and Kraaipan, North-West
      Province, South Africa. Periods of higher FECs occurred from December/January to
      March/April at Rust de Winter and at Impendle and from January to March at
      Kraaipan. Seasonal variations in body condition were evident in the goats at
      Impendle with the animals showing lower BCSs from June to October. The goats at
      Rust de Winter and at Kraaipan did not show clear seasonal variations, although
      the goats at Rust de Winter showed lower BCSs from mid-July to early December.
      The BCSs for Rust de Winter where the animals were grazed on a private farm were
      generally higher than those of the other sites, where communal grazing is
      practised.

PMID- 12237144
TI  - High-level ivermectin resistance in a field isolate of Haemonchus contortus
      associated with a low level of resistance in the larval stage: implications for
      resistance detection.
AB  - The IVPro isolate of Haemonchus contortus was isolated in 1999 after significant
      numbers of the parasite survived an ivermectin capsule treatment of grazing sheep
      acquiring a natural infection at Prospect, NSW, Australia. The isolate shows high
      level resistance to ivermectin (faecal egg count is unaffected by ivermectin oral
      treatment at 0.2mg kg(-1)). The larval LC(50), as assessed by larval development
      assays (LDAs), is only approximately two-fold higher than several susceptible
      isolates, making it difficult to detect the resistance using larval LC(50) as an
      indicator. However, the isolate shows the presence of a small proportion of the
      population (<20%) able to develop at significantly higher drug concentrations
      than the susceptible isolates. Hence, if the IVPro and susceptible isolates are
      compared at the LC(99) level, the IVPro isolate is readily identifiable as
      resistant. This degree of distinction at the LC(99) allows the IVPro isolate to
      be identified as resistant by simply observing the highest drug concentration in
      the development assay at which some larvae develop relative to the susceptible
      isolates. Assessing the development assay using this criterion allows a
      distinction between IVPro and the susceptible isolates equivalent to 10-fold
      differences in drug concentration, greatly increasing the likelihood of detecting
      the resistant isolate in routine resistance tests. This study highlights the need
      to examine this aspect of LDAs in order to detect the type of resistance
      displayed by IVPro H. contortus.

PMID- 12237145
TI  - Unfolding the secrets of the Salmonella genome to aid drug development.

PMID- 12237146
TI  - Modeling addiction: trusted experimental approaches are tried in new
      applications.
AB  - The EuroConference/Neurochemistry Winter Conference on Modeling Addiction, held
      on 6-11 April 2002 in Soelden, Austria(1) explored the question of how various
      experimental approaches, ranging from those at the level of molecular biology to
      human behavior, reflect human patterns of drug abuse and dependence and whether
      these various approaches constitute suitable predictive or homologous models to
      test novel pharmacotherapies.

PMID- 12237149
TI  - Recombinant roulette versus the apparent virtues of 'natural' cell receptor
      systems: receptor genotypes versus phenotypes.

PMID- 12237150
TI  - Chemical diversity: a function of biodiversity.

PMID- 12237152
TI  - Haemoglobin: NO transporter, NO inactivator or NOne of the above?
AB  - The structural and functional characterization of haemoglobin (Hb) exceeds that
      of any other mammalian protein. Recently, the biological role attributed to Hb
      has been extended from the classical role in the transport and exchange of the
      respiratory gases O(2) and CO(2) to include a third gaseous molecule, nitric
      oxide (NO). It is postulated that Hb might be involved in the systemic transport
      and delivery of NO to tissues and in the facilitation of O(2) release. However,
      definitive evidence for these putative activities is yet to be produced and many
      questions remain. Here we describe the present status of these hypotheses and
      their strengths and weaknesses.

PMID- 12237153
TI  - Fuzzy pharmacology: theory and applications.
AB  - Fuzzy pharmacology is a term coined to represent the application of fuzzy logic
      and fuzzy set theory to pharmacological problems. Fuzzy logic is the science of
      reasoning, thinking and inference that recognizes and uses the real world
      phenomenon that everything is a matter of degree. It is an extension of binary
      logic that is able to deal with complex systems because it does not require crisp
      definitions and distinctions for the system components. In pharmacology, fuzzy
      modeling has been used for the mechanical control of drug delivery in surgical
      settings, and work has begun evaluating its use in other pharmacokinetic and
      pharmacodynamic applications. Fuzzy pharmacology is an emerging field that, based
      on these initial explorations, warrants further investigation.

PMID- 12237154
TI  - Pharmacological inhibitors of cyclin-dependent kinases.
AB  - Cyclin-dependent kinases (CDKs) regulate the cell division cycle, apoptosis,
      transcription and differentiation in addition to functions in the nervous system.
      Deregulation of CDKs in various diseases has stimulated an intensive search for
      selective pharmacological inhibitors of these kinases. More than 50 inhibitors
      have been identified, among which >20 have been co-crystallized with CDK2. These
      inhibitors all target the ATP-binding pocket of the catalytic site of the kinase.
      The actual selectivity of most known CDK inhibitors, and thus the underlying
      mechanism of their cellular effects, is poorly known. Pharmacological inhibitors
      of CDKs are currently being evaluated for therapeutic use against cancer,
      alopecia, neurodegenerative disorders (e.g. Alzheimer's disease, amyotrophic
      lateral sclerosis and stroke), cardiovascular disorders (e.g. atherosclerosis and
      restenosis), glomerulonephritis, viral infections (e.g. HCMV, HIV and HSV) and
      parasitic protozoa (Plasmodium sp. and Leishmania sp.).

PMID- 12237155
TI  - Pharmacotherapy for Alzheimer's disease: progress and prospects.
AB  - The number of people with Alzheimer's disease has never been greater and is set
      to increase substantially in the decades ahead as the proportion of the
      population aged 65 years or more rises sharply. There is, therefore, a
      substantial and increasing need for effective pharmacotherapy. Increased
      understanding of disease pathophysiology has led to palliative treatments for
      both cognitive and non-cognitive changes in behaviour. This, together with the
      prospect of drugs that slow or perhaps even halt the course of the disease,
      raises hope that this devastating disorder will soon be more amenable to
      pharmacotherapy with new drugs that either ameliorate specific symptoms or alter
      the course of the disease.

PMID- 12237156
TI  - Mammalian peptide transporters as targets for drug delivery.
AB  - Peptide transporters are integral plasma membrane proteins that mediate the
      cellular uptake of dipeptides and tripeptides in addition to a variety of
      peptidomimetics. The carriers, which occur predominantly in the brush-border
      membranes of epithelial cells of the small intestine, lung, choroid plexus and
      kidney, contribute to absorption, distribution and elimination of their
      substrates. The cellular uptake of peptides and peptidomimetics involves the
      cotransport of protons down an inwardly directed, electrochemical proton gradient
      that provides the driving force and causes the electrogenicity of the
      translocation step. Peptide transporters represent excellent targets for the
      delivery of pharmacologically active compounds because their substrate-binding
      site can accommodate a wide range of molecules of differing size, hydrophobicity
      and charge.

PMID- 12237157
TI  - Medicinal drugs and driving: from research to clinical practice.

PMID- 12237159
TI  - Triggers and promoters of ischaemic preconditioning.

PMID- 12237160
TI  - Clues to understanding the role of estrogen receptors in mediating cardiovascular
      protection.

PMID- 12237161
TI  - Hypothesis: troponin degradation is one of the factors responsible for
      deterioration of left ventricular function in heart failure.
AB  - A hypothesis is presented that explains one of the mechanisms by which a heart
      starts to fail. The hypothesis is that myocardial function of an overloaded or
      otherwise stressed heart may become impaired by cellular troponin degradation in
      vital cardiomyocytes. The troponins (I, T and C) regulate actin-myosin
      interaction, thereby controlling contraction and relaxation. Troponins have been
      shown to be targets of activated calpain I. This enzyme, that is activated by
      elevated intracellular Ca2+ concentrations, such as occurs during ischemia,
      degrades troponins, leading to impaired interaction between actin and myosin and,
      thereby, less contractile force. Several reports about troponin degradation in
      viable myocardium support this hypothesis. Also, results are discussed that
      demonstrate the presence of immunoreactive troponin fragments in plasma under
      conditions in which myocardial necrosis can be excluded or is unlikely. The
      hypothesis implicates that release of troponin and/or troponin degradation
      products is not specific for necrotic myocardium but may occur from viable
      myocardium as well. To test this hypothesis, several lines of research are
      suggested. If the hypothesis is not rejected in the near future, the concept that
      a positive troponin test reflects 'even microscopic zones of myocardial necrosis'
      as used by the Joint ESC/ACC Committee for the Redefinition of Myocardial
      Infarction [The Joint European Society of Cardiology/American College of
      Cardiology Committee for the Redefinition of Myocardial Infarction. Myocardial
      infarction redefined-A consensus document of the Joint European Society of
      Cardiology/American College of Cardiology Committee for the Redefinition of
      Myocardial Infarction. Eur Heart J 2000;21:1502-1513], should be withdrawn.

PMID- 12237162
TI  - Molecular and cellular interface between behavior and acute coronary syndromes.
AB  - This review article integrates empirical findings from various scientific
      disciplines into a proposed psychoneuroimmunological (PNI) model of the acute
      coronary syndrome (ACS). Our starting point is an existing, mild, atherosclerotic
      plaque and a dysfunctional endothelium. The ACS is triggered by three stages. (1)
      Plaque instability: Pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha) and
      chemoattractants (MCP-1, IL-8) induce leukocyte chemoattraction to the
      endothelium, and together with other triggers such as the CD40L-CD40 co
      stimulation system activate plaque monocytes (macrophages). The macrophages then
      produce matrix metalloproteinases that disintegrate extra-cellular plaque matrix,
      causing coronary plaque instability. Acute stress, hostility, depression and
      vital exhaustion (VE) have been associated with elevated pro-inflammatory
      cytokines and leukocyte levels and their recruitment. (2) Extra-plaque factors
      promoting rupture: Neuro-endocrinological factors (norepinephrine) and cytokines
      induce vasoconstriction and elevated blood pressure (BP), both provoking a
      vulnerable plaque to rupture. Hostility/anger and acute stress can lead to
      vasoconstriction and elevated BP via catecholamines. (3) Superimposed thrombosis
      at a ruptured site: Increases in coagulation factors and reductions in
      anticoagulation factors (e.g. protein C) induced by inflammatory factors enhance
      platelet aggregation, a key stage in thrombosis. Hostility, depression and VE
      have been positively correlated with platelet aggregation. Thrombosis can lead to
      severe coronary occlusion, clinically manifested as an ACS. Thus, PNI processes
      might, at least in part, contribute to the pathogenesis of the ACS. This chain of
      events may endure due to lack of neuroendocrine-to-immune negative feedback
      stemming from cortisol resistance. This model has implications for the use of
      psychological interventions in ACS patients.

PMID- 12237163
TI  - Mesenteric and renal vascular effects of diadenosine polyphosphates (APnA).
AB  - Diadenosine polyphosphates (APnA) are endogenous dinucleoside molecules
      consisting of two adenosine moieties linked via their 5'-ribose positions by a
      variable number of phosphate groups. APnA have been shown to be present in
      different cell types and to be released from platelets as well as co-released
      with catecholamines and ATP from bovine adrenal medulla. Candidate metabolites of
      APnA are ATP, ADP, AMP and adenosine. Vascular effects induced by APnA and their
      metabolites in several models have been reported to be mediated by A1- and A2
      adenosine receptors as well as P2-purinoceptors. APnA have been demonstrated to
      differentially affect regional perfusion, to influence cardiac output and blood
      pressure as well as the reactivity of isolated blood vessels and vascular beds.
      Vascular effects of APnA vary with the number of phosphate groups linking the
      adenosine molecules. This review outlines the effects of APnA on mesenteric and
      renal circulation. The effects of the antagonists varying with the type of
      vascular bed and the heterogeneous and dynamic vascular effects of diadenosine
      polyphosphates indicate a regionally different distribution of P2X and of P2Y
      purinoceptors in resistance arteries from different vascular beds. Although APnA
      have vasoconstrictor effects on the local level, it was repeatedly confirmed that
      systemically applied APnA induce hypotensive effects. The vasoconstrictor effects
      of APnA in isolated vessels are most prominent under resting tone conditions. In
      vivo, the vasculature exhibits a vasotone which makes dilatory effects more
      likely. Information on effects of APnA in vivo is still limited despite the fact
      that these compounds already have been used in man.

PMID- 12237164
TI  - Lipopolysaccharide triggers late preconditioning against myocardial infarction
      via inducible nitric oxide synthase.
AB  - OBJECTIVE: The aim of this study was to investigate the role of inducible nitric
      oxide synthase (iNOS) as a trigger in lipopolysaccharide (LPS)-induced late
      preconditioning against myocardial infarction. METHODS: Rats were pretreated
      intraperitoneally with two different doses of LPS (0.5 or 2.5 mg/kg) or normal
      saline (control) 24 h prior to lethal myocardial ischemia. Subsequently, all rats
      were subjected to a sustained 30-min coronary occlusion followed by 180-min
      reperfusion. In the second study, total RNA and protein were extracted from
      myocardium of the control and LPS-treated rats (after 4, 6 and 24 h of treatment)
      for reverse transcription-polymerase chain reaction and Western blot analysis.
      RESULTS: In LPS (2.5 mg/kg, but not 0.5 mg/kg)-treated rats receiving no
      pharmacological intervention, the percentage of myocardial infarct within the
      area at risk and left ventricle was significantly reduced to 42+/-4 and 24+/-2%
      (P<0.01) compared with the control group. The cardioprotection was abolished by
      injection of dexamethasone (4 mg/kg x 2, i.p.) or the selective iNOS inhibitor
      aminoguanidine (300 mg/kg x 2, s.c.) before LPS treatment. The expression of iNOS
      mRNA and the iNOS protein significantly increased 4 and 6 h after administration
      of LPS (2.5 mg/kg), respectively. The increases in iNOS mRNA and protein were
      eliminated by dexamethasone. But the iNOS mRNA and protein were not detectable 24
      h after administration of LPS (2.5 mg/kg). CONCLUSIONS: These data provide
      molecular and pharmacological evidence that LPS-induced late preconditioning
      against myocardial infarction is triggered by iNOS.

PMID- 12237165
TI  - Expression of estrogen receptor subtypes and neuronal nitric oxide synthase in
      neutrophils from women and men: regulation by estrogen.
AB  - OBJECTIVES: (a) To identify the subtype of estrogen receptor (ER) expressed in
      neutrophils from premenopausal women and in neutrophils from men under different
      estrogen conditions and (b) to analyze the association between the modifications
      in the expression of ER subtypes and neuronal nitric oxide synthase (nNOS)
      expression induced by estrogen. METHODS: Neutrophils were isolated from pre
      menopausal women during different stages of the menstrual cycle and from ten men
      for in vitro estrogen incubations. RESULTS: Neutrophils from premenopausal women
      expressed both ERalpha and ERbeta subtypes which were increased in the ovulatory
      phase of the menstrual cycle. Neutrophils derived from men also expressed ERalpha
      and ERbeta but only ERalpha expression was enhanced by in vitro incubation with
      17beta-estradiol (10(-8) mol/l). In vitro incubation of neutrophils from women
      with 17beta-estradiol enhanced expression of both ER-alpha and ER-beta subtypes.
      nNOS protein was overexpressed in neutrophils from premenopausal women during the
      ovulatory phase. 17beta-Estradiol (10(-8) mol/l) also increased nNOS protein
      expression in neutrophils derived from men. Mithramycin A (10(-6) mol/l) and
      curcumin (10(-6) mol/l), prevented the upregulation of nNOS and ERalpha in
      neutrophils derived from men, suggesting the involvement of AP-1 and Sp-1
      transcription factors. CONCLUSIONS: Although the in vivo levels of circulating
      estrogen concentrations seem to be associated with overexpression of both ERalpha
      and ERbeta in neutrophils from premenopausal women, which was further confirmed
      by the in vitro experiments with neutrophils from women, in vitro incubation of
      neutrophils from men with 17beta-estradiol only increased ERalpha protein
      expression which was associated with enhanced expression of nNOS protein.

PMID- 12237166
TI  - Differential regulation of cardiac protein kinase C isozyme expression after
      aortic banding in rat.
AB  - OBJECTIVE: Protein kinase C (PKC) plays a key role in myocardial hypertrophy. To
      evaluate whether its isoforms are expressed differentially during gradual
      development of pressure-overload-induced cardiac hypertrophy, banding of the
      ascending aorta was used as an experimental model of left ventricular
      hypertrophy. METHODS: One, 7 and 30 days after sham operation or aortic banding
      in male Wistar rats, the PKC activity and the expression of the cardiac PKC
      isozymes (PKC-alpha, -delta, - epsilon and -zeta), both at the protein and the
      mRNA level, were determined in the left and right ventricle. RESULTS: Left
      ventricular hypertrophy developed rapidly as early as 1 day after aortic banding
      followed by further progression at day 7 and day 30. This was paralleled by an
      increased total PKC enzyme activity in the cytosol fraction and a selectively
      enhanced protein expression of PKC-delta (day 7, 267+/-18%; day 30, 289+/-12%)
      and PKC-alpha (day 7, 212+/-20%; day 30, 193+/-14%). The protein amount of PKC-
      epsilon was not changed in either group. This differential protein expression was
      associated with a significant increase of the absolute mRNA levels for PKC-delta
      and PKC-alpha up to 202+/-20% (day 30) and 177+/-17% (day 30), whereas
      significant alterations in the PKC- epsilon mRNA levels were not detected. A
      selective upregulation of PKC-alpha and PKC-delta, both on the protein and on the
      mRNA level, was also noted in the right ventricle during the development of right
      ventricular hypertrophy, suggesting an adaptive response following elevated left
      ventricular enddiastolic pressure after long-term aortic banding for 30 days.
      CONCLUSIONS: This study characterizes in the right and left ventricle a
      differential regulation of the dominant PKC isozymes in pressure-overload cardiac
      hypertrophy both at the protein and the mRNA level.

PMID- 12237167
TI  - Involvement of cyclin D activity in left ventricle hypertrophy in vivo and in
      vitro.
AB  - OBJECTIVE: Cardiac hypertrophy is induced by a number of stimuli and can lead to
      cardiomyopathy and heart failure. Present knowledge suggests that cell-cycle
      regulatory proteins take part in hypertrophy. We have investigated if the D-type
      cyclins are involved in cardiac hypertrophy. METHODS: The expression and activity
      of the D-type cyclins and associated kinases in cardiomyocytes were studied
      during angiotensin II- and pressure overload-induced hypertrophy in rats (Rattus
      norvegicus) and in isolated, neonatal cardiomyocytes. Expression of the D-type
      cyclins was manipulated pharmacologically and genetically in neonatal myocytes.
      RESULTS: In the left ventricle, there was a low, constitutive expression of the D
      type cyclins, which may have a biological role in normal, adult myocytes. The
      protein level and the associated kinase activity of the D-type cyclins were up
      regulated during hypertrophic growth. The increase in cyclin D expression could
      be mimicked in vitro in neonatal cardiac myocytes. Interestingly, the cyclin Ds
      were up-regulated by hypertrophic elicitors that stimulate different signalling
      pathways, suggesting that cyclin D expression is an inherent part of cardiac
      hypertrophy. Treatment of myocytes with the compound differentiation inducing
      factor 1 inhibited expression of the D-type cyclins and impaired hypertrophic
      growth induced by angiotensin II, phenylephrine and serum. The response to
      hypertrophic elicitors could be restored in differentiation inducing factor 1
      treated myocytes by expressing cyclin D2 from a heterologous promoter.
      CONCLUSION: Our results point to the D-type cyclins as important regulators of
      cardiac hypertrophy. This supports the notion that cell-cycle regulatory proteins
      regulate hypertrophic growth.

PMID- 12237168
TI  - Effect of ischemia-reperfusion on heart mitochondria from hyperthyroid rats.
AB  - OBJECTIVE: We investigated the effect of hyperthyroidism on the functional
      response of mitochondria to ischemia-reperfusion and its relationship with
      changes in mitochondrial susceptibility to stress conditions. METHODS:
      Hyperthyroidism was elicited by ten daily intraperitoneal injections of T3 (10
      microg/100 g body weight). Mitochondria were isolated at 3000xg (M3) from
      homogenates of hearts perfused by the Langendorff technique after either 25 min
      reperfusion following 20 min ischemia or 45 min perfusion (controls). Rates of O2
      consumption and H2O2 release with complex II-linked substrate, capacity to remove
      H2O2, extent of oxidative damage, levels of liposoluble antioxidants, such as
      ubiquinols and vitamin E, and susceptibility to Ca2+ -induced swelling were
      determined. RESULTS: During reperfusion, hyperthyroid hearts displayed a
      significant tachycardia together with a low functional recovery. In comparison to
      the respective controls, mitochondria from both euthyroid and hyperthyroid hearts
      subjected to ischemia-reperfusion protocol exhibited decreases in the rate of O2
      consumption, capacity to remove H2O2, and concentration of antioxidants, and
      increases in the rate of H2O2 release, concentration of hydroperoxides and
      protein-bound carbonyls, and susceptibility to Ca2+ -induced swelling. Such
      changes were higher in mitochondria from hyperthyroid hearts. The increase in the
      protein percent content and cytochrome oxidase activity of a mitochondrial
      fraction isolated at 8000xg (M8) from hyperthyroid hearts after reperfusion,
      suggests that the decline of mitochondrial respiration of M3 fraction could be
      due to the degradation of the oldest, mature mitochondria endowed of high
      oxidative capacity, but low antioxidant capacity, which would be lost by heavy
      mitochondrial fraction and recovered in the light fraction. CONCLUSIONS: The
      higher susceptibility to ischemia-reperfusion of the heart from hyperthyroid
      animals is associated with a significant increase in mitochondrial dysfunction.

PMID- 12237169
TI  - C-Reactive protein augments inducible nitric oxide synthase expression in
      cytokine-stimulated cardiac myocytes.
AB  - OBJECTIVE: Nitric oxide (NO) production by inducible NO synthase (iNOS) can exert
      negative inotropic and cytotoxic effects on cardiac myocytes and may play an
      important role in the pathogenesis of cardiac dysfunction and remodeling. An
      elevated serum level of C-reactive protein (CRP) is an important predictive
      factor for cardiac disorders including acute myocardial infarction and dilated
      cardiomyopathy. The basic mechanisms responsible for this association are not
      clear; CRP may merely be a marker of inflammation with no specific role in the
      pathogenesis of cardiac disease or may directly modulate the disease process. We
      investigated the effects of CRP on iNOS expression and subsequent NO synthesis in
      rat cardiac myocytes, and the mechanism by which CRP exerts its effects. METHODS:
      NO production by culture neonatal rat cardiac myocytes was determined by
      measurement of nitrite contents in the culture medium. The expression of iNOS
      mRNA and protein were measured by reverse transcription-polymerase chain reaction
      and Western blotting, respectively. The levels of nuclear factor (NF)-kappaB
      proteins were analyzed by a gel retardation assay. RESULTS: Incubation of cardiac
      myocytes with interleukin-1beta (IL-1beta; 10 ng/ml) caused a significant
      increase in nitrite production. CRP significantly increased the IL-1beta-induced
      nitrite production in a dose-dependent manner (10-100 microg/ml). Incubation with
      IL-1beta induced the expression of iNOS mRNA and protein in cardiac myocytes, and
      CRP enhanced their expression. Addition of IL-1beta activated NF-kappaB in
      cardiac myocytes, while CRP did not affect IL-1beta-induced NF-kappaB activation.
      CONCLUSIONS: These results indicated that CRP directly enhances NO synthesis in
      IL-1beta-stimulated cardiac myocytes through an NF-kappaB-independent mechanism.

PMID- 12237170
TI  - Cardiac-enriched LIM domain protein fhl2 is required to generate I(Ks) in a
      heterologous system.
AB  - OBJECTIVE: Co-expression of the KvLQT1 and minK potassium channel subunits is
      required to recapitulate I(Ks), the slow component of the cardiac delayed
      rectifier current, and mutations in either gene cause the congenital Long QT
      syndrome. It is becoming increasingly well-recognized that multiprotein channel
      complexes containing proteins capable of modulating channel function assemble at
      the plasma membrane. Thus, the aim of our study was to identify proteins involved
      in I(Ks) modulation. METHODS AND RESULTS: Using a yeast-two-hybrid screen with
      the intracytoplasmic C-terminus of minK as bait, we identified the cardiac
      enriched four-and-a-half LIM domain-containing protein (fhl2) as a potential minK
      partner. We show interaction between the two proteins in GST pulldown assays and
      demonstrate overlapping subcellular localization using immunocytochemistry of
      transfected cells supporting a potential interaction. At the functional level,
      expression of KvLQT1and minK in HEK cells, which lack endogenous fhl2 protein,
      generated I(Ks) only when fhl2 was co-expressed. By contrast, in CHO-K1 cells,
      which express fhl2 endogenously, I(Ks) was suppressed by anti-fhl2 antisense
      which did not affect the currents generated by KvLQT1alone. CONCLUSION: These
      data indicate that at least in heterologous cells, the generation of I(Ks)
      requires fhl2 as an additional protein component.

PMID- 12237171
TI  - Putative binding sites for benzocaine on a human cardiac cloned channel (Kv1.5).
AB  - OBJECTIVES: It has been demonstrated that at nanomolar concentrations benzocaine
      increased, whereas at micromolar concentrations, it blocked hKv1.5 channels in a
      voltage-dependent manner and modified the voltage-dependence of channel
      activation. The present study was undertaken to localize the putative binding
      sites involved in the 'agonists' and blocking effects of benzocaine. METHODS:
      Experiments were carried out on wild-type and site directed mutated hKv1.5
      channels stably expressed on Ltk(-) cells using the whole-cell patch-clamp.
      RESULTS: At 35 mM [K+](i) the voltage-dependent unblock produced by 500 microM
      benzocaine was preserved at both 4 and 140 mM [K+](o). Mutations located in the
      inner mouth of the pore (T477S, T505A, L508M and V512M) abolished the agonist but
      increased the blocking effects of benzocaine. Intracellular application of
      tetraethylammonium (3 mM) abolished the 'agonist' effects whereas the blocking
      effects of benzocaine remained unaltered. Block induced by benzocaine and
      intracellular tetraethylammonium was additive. In contrast, the combination of
      benzocaine and bupivacaine (>25 microM) produced less blockade than bupivacaine
      alone. However, mutation of the extracellular residue R485Y did not modify the
      effects of benzocaine. Extracellular application of tetraethylammonium (100 mM)
      did not modify the agonist effects of benzocaine, but abolished the voltage- and
      time-dependence of benzocaine-induced block. CONCLUSIONS: The results suggested
      that benzocaine binds with high affinity to an intracellular binding site to
      produce 'agonist' effects and to a low affinity subsite, which is also located in
      the inner mouth, to produce the blocking effects. Furthermore, benzocaine and
      extracellular K(+) interact to modify the voltage-dependence of channel opening.

PMID- 12237172
TI  - Effects of a 'healthy' diet and of acute and long-term vitamin C on vascular
      function in healthy older subjects.
AB  - OBJECTIVE: Aging is associated with endothelial dysfunction. We studied the acute
      and longer-term effects of vitamin C compared to a 'Mediterranean-type' diet on
      endothelial function in healthy older subjects. METHODS: Bilateral venous
      occlusion plethysmography was used to measure forearm blood flow in subjects aged
      57-80 years. Responses to cumulative intra-arterial doses of the endothelium
      dependent dilator bradykinin (BK; n=56; 20, 40, 80 pmol/min) and the nitric oxide
      donor glyceryl trinitrate (GTN; n=54; 4, 8, 16 nmol/min), were determined alone
      and in the presence of vitamin C (25 mg/min). We then randomised 54 subjects to a
      'healthy' diet (n=18), vitamin C (1 g/day; n=18) or placebo for 6 weeks and
      reassessed endothelial and smooth muscle function. RESULTS: Acute intra-arterial
      vitamin C did not alter dilatation to BK or GTN. Similar increases in plasma
      vitamin C occurred on oral vitamin C (83+/-4 to 135+/-8 micromol/l) and 'healthy'
      diet (84+/-5 to 135+/-27 micromol/l; P<0.01 for both), with no change seen on
      placebo. Treatment with a 'healthy' diet but not oral vitamin C improved
      endothelium-dependent (P=0.043) and endothelium-independent dilatation (P=0.011).
      CONCLUSIONS: A 'Mediterranean-type' diet rich in vitamin C improves vascular
      function. Neither acute intra-arterial nor sustained administration of oral
      vitamin C improves vascular function in healthy older subjects.

PMID- 12237173
TI  - TLR4-mediated inflammatory activation of human coronary artery endothelial cells
      by LPS.
AB  - OBJECTIVE: Blood levels of cytokines are commonly elevated in severe congestive
      heart failure (CHF) and in coronary artery disease (CAD). While the adverse
      effects of cytokines on contractile function and myocardial cell integrity are
      well studied, little is known on whether cardiac cells are only targets or active
      players in these inflammatory reactions. METHODS AND RESULTS: We tested if human
      coronary artery endothelial cells (HCAEC) may become a source of cytokine and
      adhesion molecule expression when stimulated with bacterial lipopolysaccharide
      (LPS). Analysis of HCAEC supernatants by ELISA identified enhanced secretion of
      IL-6, IL-8, and MCP-1 while endothelin-1 was not increased. IL-1beta, IL-10, or
      TNF-alpha were not detectable by ELISA while RT-PCR revealed enhanced mRNA
      expression of IL-1beta and TNF-alpha but not IL-10. FACS analysis showed an LPS
      induced upregulation of ICAM-1, VCAM, and ELAM-1. LFA-1 could not be detected. We
      further characterized receptors involved in LPS-induced signaling. Our results
      indicate that activation of HCAEC by LPS requires Toll-like receptor (TLR) 4.
      Pretreating the cells with the 3-hydroxy-3-methylglutaryl CoA (HMG CoA) reductase
      inhibitor Cerivastatin reduced IL-6 release. CONCLUSIONS: Taken together, our
      results indicate that activated HCAEC may act as inflammatory cells and thus
      directly contribute to the progression of CHF and CAD.

PMID- 12237174
TI  - Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary
      plaque stabilization in miniature pigs.
AB  - OBJECTIVE: To study the effect of dietary cholesterol withdrawal on size and
      composition of LDL-hypercholesterolemia-induced coronary plaques in miniature
      pigs. METHODS: Pigs were on normal chow (control group), on a cholesterol-rich
      diet for 37 weeks (hypercholesterolemic group) or on a cholesterol-rich diet
      followed by normal chow for 26 weeks (cholesterol withdrawal group). Endothelial
      function was assessed with quantitative angiography after intracoronary infusion
      of acetylcholine, plaque load with intra-coronary ultrasound and plaque
      composition with image analysis of cross-sections. The effect of porcine serum on
      coronary smooth muscle cell (SMC) function was studied in vitro. RESULTS:
      Cholesterol-rich diet caused LDL-hypercholesterolemia, increased plasma levels of
      oxidized LDL (ox-LDL) and C-reactive protein (CRP), and induced endothelial
      dysfunction and coronary atherosclerosis. Dietary cholesterol withdrawal lowered
      LDL, ox-LDL and CRP. It restored endothelial function, did not affect plaque size
      but decreased lipid, ox-LDL and macrophage content. Smooth muscle cells and
      collagen accumulated within the plaque. Increased smoothelin-to-alpha-smooth
      muscle actin ratio indicated a more differentiated SMC phenotype. Cholesterol
      lowering reduced proliferation and apoptosis. In vitro, hypercholesterolemic
      serum increased SMC apoptosis and decreased SMC migration compared to non
      hypercholesterolemic serum. CONCLUSIONS: Cholesterol lowering induced coronary
      plaque stabilization as evidenced by a decrease in lipids, ox-LDL, macrophages,
      apoptosis and cell proliferation, and an increase in differentiated SMC and
      collagen. Increased migration and decreased apoptosis of SMC may contribute to
      the disappearance of the a-cellular core after lipid lowering.

PMID- 12237175
TI  - Intrauterine undernutrition: expression and activity of the endothelial nitric
      oxide synthase in male and female adult offspring.
AB  - OBJECTIVE: Epidemiological studies suggest that intrauterine undernutrition plays
      an important role in the development of arterial hypertension in adulthood. In an
      attempt to define the mechanisms whereby blood pressure may be raised, we have
      hypothesized that arteries from offspring of nutritionally restricted dams
      exhibit abnormalities in the endothelial function and in nitric oxide synthesis.
      In order to investigate the existence of potential gender differences on the
      effects of intrauterine undernutrition, both male and female offspring of
      pregnant Wistar rats on normal and restricted diets were studied in adulthood.
      METHODS: Female pregnant Wistar rats were fed either normal or 50% of the normal
      intake diets, during the whole gestational period. At 14 weeks of age, the rats
      were used for the study of vascular reactivity, eNOS and iNOS gene expression,
      eNOS activity and, in the case of females, estrogen levels. RESULTS: Intrauterine
      undernutrition induced hypertension in both male and female offspring, but
      hypertension was more severe in male rats. Endothelium-intact aortic rings from
      male and female rats in the restricted diet group exhibited increased responses
      to norepinephrine, decreased vasodilation to acetylcholine and unaltered
      responses to sodium nitroprusside in comparison to aortic rings from control
      rats. No gender-related differences were observed in the vascular reactivity
      studies. Intrauterine undernutrition promoted decreased gene expression for eNOS
      in aorta isolated from male, but not female, offspring, reduction in eNOS
      activity in both male and female offspring and impairment in synthesis of
      estrogen in female offspring. CONCLUSION: Our data show that intrauterine
      undernutrition: (1) induces hypertension both in the male and female offspring,
      hypertension being more severe in male than in female rats; (2) alters
      endothelium-dependent responses in aortas from the resulting offspring. The
      endothelial dysfunction is associated with a decrease in activity/expression of
      eNOS in aortas from male offspring. The mechanism involved in altered response to
      ACh in female offspring might be a consequence of reduction in estrogen levels
      leading to reduced eNOS activity.

PMID- 12237176
TI  - The molecular site of action of K(ATP) channel inhibitors determines their
      ability to inhibit iNOS-mediated relaxation in rat aorta.
AB  - OBJECTIVE: ATP-sensitive potassium (K(ATP)) channels are important modulators of
      vascular tone. Abnormal activation of these channels via over production of
      nitric oxide (NO) has been implicated in endotoxin-induced hypotension. However,
      based on studies with the sulphonylurea K(ATP) channel inhibitor, glibenclamide,
      there is little evidence to support their role in mediating vasorelaxation to
      endotoxin in isolated blood vessels. In the present study, we investigated
      whether NO derived from inducible NO synthase (iNOS) modulates K(ATP) channel
      function in rat aorta. METHODS: Using standard organ bath techniques, the effects
      of structurally unrelated K(ATP) channel inhibitors on the vasorelaxant responses
      to L-arginine (iNOS substrate), NO, levcromakalim (K(ATP) channel opener) and
      forskolin were investigated in endothelium-denuded aortic rings exposed to
      endotoxin (lipopolysaccharide) for 4 h. RESULTS: Relaxation evoked by L-arginine
      was unaffected by glibenclamide and the pinacidil-derived inhibitor, PNU-99963,
      but was significantly attenuated by the iNOS inhibitor, 1400W, as well as by PNU
      37883A, Ba2+, 4-aminopyridine and tetraethylammonium, all known inhibitors of the
      K(ATP) channel pore. In addition, endotoxin potentiated responses to
      levcromakalim and markedly reduced the efficacy of glibenclamide, and to a much
      lesser extent, PNU-37883A. Forskolin responses were unaffected by glibenclamide
      or PNU-37883A under control conditions, but were significantly potentiated
      following endotoxin treatment, an effect reversed by PNU-37883A, but not
      glibenclamide. CONCLUSION: K(ATP) channels contribute to iNOS-mediated
      relaxation. However, the ability of sulphonylurea receptor-binding agents, but
      not those binding directly to the pore, to inhibit K(ATP) channels, is greatly
      diminished in the presence of endotoxin.

PMID- 12237177
TI  - Increased intimal hyperplasia in experimental vein graft stenting compared to
      arterial stenting: comparisons in a new rabbit model of stent injury.
AB  - BACKGROUND: In-stent restenosis due to intimal hyperplasia is an important
      clinical problem. Animal models of stent injury are limited by inconsistent
      arterial responses to stenting, and less intimal hyperplasia than diseased human
      vessels. To address these issues, we aimed to compare the degree of intimal
      hyperplasia in stented rabbit jugular-carotid interposition grafts (vein grafts)
      versus stented carotid arteries. METHODS: Jugular-carotid vein grafts were
      constructed in rabbits, then stented or left unstented. Carotid arteries were
      treated with similar stents or left instrumented only. After 3 or 28 days,
      vessels were perfusion fixed, embedded in resin, and sections were cut with a
      diamond saw. Intimal and medial thicknesses were measured in stained sections.
      RESULTS: After 3 days, inflammatory changes were observed in the intima of all
      stented vessels. After 28 days, intimal thickness in stented vein grafts was 2
      fold greater than in control vein grafts and approximately 4-fold greater than in
      stented carotid arteries. In addition, the intimal hyperplasia response was
      markedly more consistent in stented vein grafts compared with stented carotid
      arteries. CONCLUSIONS: Stent deployment in experimental vein grafts results in
      increased and more reproducible smooth muscle cell intimal hyperplasia than
      carotid arterial stenting. This is a promising small-animal model for
      investigating the intimal response to stenting.

PMID- 12237178
TI  - Attention, novelty, and pain.

PMID- 12237179
TI  - Cancer pain at the end of life: a biopsychosocial perspective.

PMID- 12237180
TI  - Analgesic profile of intrathecal P2X(3) antisense oligonucleotide treatment in
      chronic inflammatory and neuropathic pain states in rats.
AB  - Extracellular adenosine triphosphate (ATP), acting at P2X ionotropic receptors,
      is implicated in numerous sensory processes. Exogenous ATP has been shown to be
      algogenic in both animals and humans. Research focus has been directed towards
      the P2X(3) receptor, as it is preferentially expressed on nociceptive C-fibers
      and its implication in pain processing is supported by an altered nociceptive
      phenotype in P2X(3) knock-out mice. In order to further characterize the role of
      P2X(3) receptor activation in nociception, we evaluated the effects of continuous
      intrathecal administration of P2X(3) antisense oligonucleotides for 7 days in the
      rat. P2X(3) receptor antisense oligonucleotide treatment significantly decreased
      nociceptive behaviors observed after injection of complete Freund's adjuvant
      (CFA), formalin or alphabeta-methylene ATP into the rat's hind paw. The anti
      hyperalgesic effects of the antisense treatment in the CFA model of inflammatory
      pain were dose related. Similar effects were observed with two distinct P2X(3)
      antisense oligonucleotides. These behavioral effects were significantly
      correlated with a decrease in P2X(3) receptor protein expression in the dorsal
      root ganglia (DRG). In contrast, a decrease in P2X(3) receptor protein expression
      in the DRG did not affect nociceptive behavior in the carrageenan model of acute
      thermal hyperalgesia. P2X(3) receptor antisense oligonucleotide treatment also
      significantly reduced mechanical allodynia observed after spinal nerve ligation.
      Overall, the present data demonstrate that activation of P2X(3) receptors
      contribute to the expression of chronic inflammatory and neuropathic pain states
      and that relief form these forms of chronic pain might be achieved by selective
      blockade of P2X(3 )receptor expression or activation.

PMID- 12237181
TI  - Attentional modulation of the nociceptive processing into the human brain:
      selective spatial attention, probability of stimulus occurrence, and target
      detection effects on laser evoked potentials.
AB  - Laser evoked potentials (LEPs) are brain responses to activation of skin
      nociceptors by laser heat stimuli. LEPs consist of three components: N1, N2, and
      P2. Previous reports have suggested that in contrast to earlier activities (N1),
      LEPs responses after 230-250 ms (N2-P2) are modulated by attention to painful
      laser stimuli. However, the experimental paradigms used were not designed to
      specify the attentional processes involved in these LEP modulations. We
      investigated the effects of selective spatial attention and oddball tasks on
      LEPs. CO(2) laser stimuli of two different intensities were delivered on the
      dorsum of both hands of ten subjects. One intensity was frequently presented, and
      the other rarely. Subjects were asked to pay attention to stimuli delivered on
      one hand and to count rare stimuli, while ignoring stimuli on the other hand.
      Frequent and rare attended stimuli evoked enhanced N160 (N1) and N230 (N2)
      components in comparison to LEPs from unattended stimuli. Both components showed
      scalp distribution contralateral to the stimulus location. The vertex P400 (P2)
      was unaffected by spatial attention and stimulus location, but its amplitude
      increased after rare stimuli, whether attended or unattended. An additional
      parietal P600 component was induced by the attended rare stimuli. It is suggested
      that several attentional processes can modify nociceptive processing in the brain
      at different stages. LEP activities in the time-range of N1 and N2 (120-270 ms)
      showed evidence of processes modulated by the direction of spatial attention.
      Conversely, processes underlying P2 (400 ms) were not affected by spatial
      attention, but by the probability of the stimulus. This probability effect was
      not due to P3b-related processes that were observed at a later latency (600 ms).
      Indeed, P600 could be seen as a P3b evoked by conscious detection of rare
      targets.

PMID- 12237182
TI  - Sensory dysfunction in burning mouth syndrome.
AB  - Our preliminary observations on a small group of burning mouth syndrome (BMS)
      patients indicated a change in the non-nociceptive, tactile sensory function in
      BMS and provided evidence for the hypothesis of a neuropathic etiology of BMS. In
      the present clinical study on a group of 52 BMS patients, we used quantitative
      sensory tests (QST) in addition to the blink reflex (BR) recordings in order to
      gain further insight into the neural mechanisms of BMS pain. Based on
      electrophysiologic findings, the BMS patients could be grouped into four
      different categories: (1) The results of the BR were suggestive of brainstem
      pathology or peripheral trigeminal neuropathy in ten (19%) patients. In most of
      the cases, the abnormalities in the BR seemed to represent subclinical changes of
      the trigeminal system. (2) Increased excitability of the BR was found in the form
      of deficient habituation of the R2 component of the BR in 11 (21%) of the
      patients. Two of these patients also showed signs of warm allodynia in QST. (3)
      One or more of the sensory thresholds were abnormal indicating thin fiber
      dysfunction in altogether 35 patients (76%) out of the 46 tested with QST. Thirty
      three of these patients showed signs of hypoesthesia. (4) There were only five
      patients with normal findings in both tests. The present findings with strong
      evidence for neuropathic background in BMS will hopefully provide insights for
      new therapeutic strategies.

PMID- 12237183
TI  - Enhanced temporal summation of second pain and its central modulation in
      fibromyalgia patients.
AB  - We have previously shown that fibromyalgia (FMS) patients have enhanced temporal
      summation (windup) and prolonged decay of heat-induced second pain in comparison
      to control subjects, consistent with central sensitization. It has been
      hypothesized that sensory abnormalities of FMS patients are related to deficient
      pain modulatory mechanisms. Therefore, we conducted several analyses to further
      characterize enhanced windup in FMS patients and to determine whether it can be
      centrally modulated by placebo, naloxone, or fentanyl. Pre-drug baseline ratings
      of FMS and normal control (NC) groups were compared with determine whether FMS
      had higher pain sensitivity in response to several types of thermal tests used to
      predominantly activate A-delta heat, C heat, or cold nociceptors. Our results
      confirmed and extended our earlier study in showing that FMS patients had larger
      magnitudes of heat tap as well as cold tap-induced windup when compared with age-
      and sex-matched NC subjects. The groups differed less in their ratings of sensory
      tests that rely predominantly on A-delta-nociceptive afferent input. Heat and
      cold-induced windup were attenuated by saline placebo injections and by fentanyl
      (0.75 and 1.5 microg/kg). However, naloxone injection had the same magnitudes of
      effect on first or second pain as that produced by placebo injection. Hypoalgesic
      effects of saline placebo and fentanyl on windup were at least as large in FMS as
      compared to NC subjects and therefore do not support the hypothesis that pain
      modulatory mechanisms are deficient in FMS. To the extent that temporal summation
      of second pain (windup) contributes to processes underlying hyperalgesia and
      persistent pain states, these results indirectly suggest that these processes can
      be centrally modulated in FMS patients by endogenous and exogenous analgesic
      manipulations.

PMID- 12237184
TI  - Trigeminal c-Fos expression and behavioral responses to pulpal inflammation in
      ferrets.
AB  - Injury to peripheral dental tissues evokes dynamic alternations in central
      sensory pathways. We have previously reported that transient stimulation of the
      dental pulp with noxious heat evokes the induction of the immediate early gene
      product Fos in the transitional region between subnucleus interpolaris and
      caudalis (Vi/Vc) and subnucleus caudalis (Vc). A question arises as to whether
      similar changes occur in response to inflammation to the tooth pulp. In this
      study, the effects of pulpal inflammation produced by bacterial
      lipopolysaccharide (LPS) on face-grooming behavior and trigeminal Fos expression
      were examined. Face-grooming behaviors were recorded daily for 3 days pre- and
      24, 48 and 72 h post- LPS or saline application. All animals were perfused 72 h
      post- LPS or saline application. Brainstems were processed for Fos-like
      immunoreactivity (Fos-LI). Teeth were processed for H&E staining. Histological
      examination of LPS-treated teeth revealed features of an acute pulpitis.
      Moreover, LPS-treated animals showed greater face-grooming activity (i.e. tongue
      protrusions) directed to the injured tooth than the sham-operated group. The
      number of Fos-positive neurons was greater in the trigeminal subnucleus caudalis
      (Vc) and the transitional regions (Vi/Vc) in LPS-treated animals compared with
      sham-operated animals, and greater in the deeper laminae than the superficial
      laminae of each trigeminal region. LPS treatment did not evoke Fos expression in
      the rostral trigeminal regions above Vi/Vc. These results demonstrate that LPS
      induced pulpal inflammation results in significant alterations in the Vi/Vc and
      Vc, and such changes may underlie the observed nociceptive behavioral responses
      and may play an important role in producing a symptomatic pulpitis in humans.

PMID- 12237185
TI  - Antinociceptive effect of cardiopulmonary chemoreceptor and baroreceptor reflex
      activation in the rat.
AB  - The effect on the nociceptive tail-flick (TF) reflex of cardiopulmonary
      chemoreceptor and arterial baroreceptor activation, producing Bezold-Jarisch like
      and baro-reflex responses, respectively, was analysed in lightly halothane
      anaesthetized rats. Intra-cardiac administration of phenylbiguanide (5-100
      microg/kg, into the right atrium) or veratrine (30-150 microg/kg, into the left
      ventricle), which both elicited the characteristic Bezold-Jarisch-like
      cardiovascular reflex responses (hypotension and bradycardia), produced a dose
      dependent increase in TF latency. A similar inhibitory influence on the TF reflex
      was noted upon baroreflex activation by acute administration of phenylephrine (15
      50 microg/kg i.v.) or aortic depressor nerve stimulation (100-400 microA). As
      expected from the involvement of local excitatory amino acid receptors in both
      vagally mediated cardiovascular reflex responses and inhibition of the TF reflex,
      microinjections of kynurenic acid (3 nmol/0.1 microl), an N-methyl-D-aspartate
      (NMDA) and non-NMDA receptor antagonist, into the nucleus tractus solitarius,
      prevented the cardiovascular responses as well as the concomitant increase in TF
      latency produced by cardiopulmonary chemoreceptor and baroreceptor stimulations.
      The present data show that induction of the cardiopulmonary chemoreceptor and
      baroreceptor reflexes produces an antinociceptive effect which can be assessed
      using the TF test, and that glutamate ionotropic receptors within the nucleus
      tractus solitarius mediate this effect.

PMID- 12237186
TI  - Immediate effects of dry needling and acupuncture at distant points in chronic
      neck pain: results of a randomized, double-blind, sham-controlled crossover
      trial.
AB  - To evaluate immediate effects of two different modes of acupuncture on motion
      related pain and cervical spine mobility in chronic neck pain patients compared
      to a sham procedure. Thirty-six patients with chronic neck pain and limited
      cervical spine mobility participated in a prospective, randomized, double-blind,
      sham-controlled crossover trial. Every patient was treated once with needle
      acupuncture at distant points, dry needling (DN) of local myofascial trigger
      points and sham laser acupuncture (Sham). Outcome measures were motion-related
      pain intensity (visual analogue scale, 0-100 mm) and range of motion (ROM). In
      addition, patients scored changes of general complaints using an 11-point verbal
      rating scale. Patients were assessed immediately before and after each treatment
      by an independent (blinded) investigator. Multivariate analysis was used to
      assess the effects of true acupuncture and needle site independently. For motion
      related pain, use of acupuncture at non-local points reduced pain scores by about
      a third (11.2 mm; 95% CI 5.7, 16.7; P = 0.00006) compared to DN and sham. DN led
      to an estimated reduction in pain of 1.0 mm (95% CI -4.5, 6.5; P = 0.7). Use of
      DN slightly improved ROM by 1.7 degrees (95% CI 0.2, 3.2; P = 0.032) with use of
      non-local points improving ROM by an additional 1.9 degrees (95% CI 0.3, 3.4; P =
      0.016). For patient assessment of change, non-local acupuncture was significantly
      superior both to Sham (1.7 points; 95% CI 1.0, 2.5; P = 0.0001) and DN (1.5
      points; 95% CI 0.4, 2.6; P = 0.008) but there was no difference between DN and
      Sham (0.1 point; 95% CI -1.0, 1.2; P = 0.8). Acupuncture is superior to Sham in
      improving motion-related pain and ROM following a single session of treatment in
      chronic neck pain patients. Acupuncture at distant points improves ROM more than
      DN; DN was ineffective for motion-related pain.

PMID- 12237187
TI  - Blinding effectiveness and association of pretreatment expectations with pain
      improvement in a double-blind randomized controlled trial.
AB  - Patient, provider, and clinical investigator expectations concerning treatments
      are believed to play important roles in patient response. This study examined the
      association of patient and research nurse/physician pretreatment expectations of
      pain relief with actual pain relief, the accuracy of patient and research nurse
      guesses about patient medication assignment, and changes in research nurse and
      patient pain relief expectations over the course of a randomized double-blind
      trial of amitriptyline versus an active placebo for patients with chronic pain
      and spinal cord injuries (SCI). Patient expectations of pain relief with
      amitriptyline were associated significantly with actual pain decrease for
      patients in the amitriptyline, but not placebo, condition. Research
      nurse/physician expectations did not predict patient pain relief. Both patients
      and the research nurse were able to guess patient medication assignment at a rate
      significantly greater than chance. The research nurse's, but not the patients',
      expectations of pain relief with amitriptyline decreased significantly over the
      course of the study. These findings have implications for future randomized
      controlled trials. Fully double-blind conditions are very difficult to achieve,
      and it is informative to assess patient and research clinician expectations and
      guesses regarding medication assignment.

PMID- 12237188
TI  - Postsurgical pain outcome assessment.
AB  - Reliable and valid measures of pain are essential for conducting clinical trials
      of pain treatments. Perhaps the most important aspect of a pain measure's
      validity is its sensitivity, or ability to detect changes in pain over time and
      due to treatment. Several factors may affect a measure's sensitivity, including
      the complexity of the rating task for the measure, the number of pain intensity
      levels assessed by the measure, the dimension of pain assessed (e.g. pain
      intensity vs. pain relief), and the number of individual ratings (e.g. single
      rating vs. composite score) used to create the measure. The purpose of this study
      was to compare the relative sensitivity of three measures of outcome and a
      composite made up of all three measures for detecting analgesic effects in two
      samples of persons participating in a randomized controlled trial. One hundred
      and twenty-three patients who had undergone knee surgery and 124 women who had
      undergone a laparotomy were given one of three medications in the day after their
      surgery: morphine, ketorolac, or placebo. Two measures of pain intensity (a
      visual analog scale (VAS) and a 4-point verbal rating scale (VRS)) were
      administered at baseline, and these measures plus a 5-point VRS of pain relief
      were administered at 16 additional time points up to 24 h following surgery. As
      predicted, we found variability in the sensitivity of the outcome measures used
      in these studies, with the 4-point VRS showing less sensitivity than the VAS or
      relief ratings. However, contrary to our prediction, a composite measure of
      outcome made up of all three measures was not consistently superior to the
      individual measures for detecting treatment effects. Finally, we found that pain
      relief ratings were related to, but also distinct from, change in pain intensity
      as measured by changes in pain intensity ratings from baseline to each
      postmedication assessment point. These findings have important implications for
      the assessment of pain in clinical trials.

PMID- 12237189
TI  - VR1, but not P2X(3), increases in the spared L4 DRG in rats with L5 spinal nerve
      ligation.
AB  - We investigated the expression of two candidate transducers of noxious stimuli in
      peripheral tissues, the vanilloid receptor subtype 1 (VR1) and the P2X(3), a
      subunit of the ionotropic P2X receptor for ATP, in spared L4 DRG neurons
      following L5 spinal nerve ligation, a neuropathic pain model. VR1 mRNA expression
      increased in the small- and medium-sized DRG neurons from the first to 28th day
      after injury, and this up-regulation corresponded well with the development and
      maintenance of thermal hyperalgesia of the hind paw. The increase in VR1
      immunoreactive (ir) neurons was confirmed at the third day after surgery. In
      contrast, there was no change in expression of P2X(3) mRNA over 4 weeks after
      ligation, or in the percentage of P2X(3)-ir neurons observed 3 days after
      surgery. Our data suggests that increased VR1 in the spared L4 DRG may contribute
      to the exaggerated heat response observed in this neuropathic pain model. Taken
      together with the previous reports that P2X(3) expression increases in the spared
      DRG neurons in other neuropathic pain models, there appears to be differences in
      the phenotypic changes and pathomechanisms of the various neuropathic pain
      models.

PMID- 12237190
TI  - Expression of neurotrophic factors in the dorsal root ganglion in a rat model of
      lumbar disc herniation.
AB  - A variety of molecules released by inflammatory reactions in the dorsal root and
      dorsal root ganglion (DRG) may play important roles in the pathology of neuronal
      abnormalities in lumbar disc herniation. In order to elucidate the
      pathophysiological mechanisms of painful radiculopathy, secondary to lumbar disc
      herniation, we evaluated pain-related behavior and the change of nerve growth
      factor (NGF) and brain-derived neurotrophic factor (BDNF) expression in the DRG
      and dorsal root using a rat model of lumbar disc herniation. In the nucleus
      pulposus (NP) group, the left L4/5 nerve roots were exposed after
      hemilaminectomies and autologous intervertebral discs, which were obtained from
      coccygeal intervertebral discs, were implanted on each of the exposed nerve roots
      without mechanical compression. Rats in the NP group, but not the sham-operated
      rats, developed mechanical allodynia on the ipsilateral hind paw for 1 day after
      surgery and showed a significant increase in the number of NGF-immunoreactive
      (IR) cells in the nerve root and DRG. NGF-IR cells in the nerve root and DRG
      included macrophages and Schwann cells, because these cells were labeled for NGF
      and ED-1 or glial fibrillary acid protein by dual immunostaining. A significant
      increase in the percentage of BDNF-IR neurons in the DRG was observed in the NP
      group at 3 days after surgery and the increase in BDNF mRNA expression was
      confirmed using in situ hybridization histochemistry and reverse transcription
      polymerase chain reaction. We also injected NGF into the endoneurial space of the
      normal rat spinal nerve root and found that the NGF injection produced dose
      dependent mechanical allodynia on the ipsilateral hind paw at 1 day after surgery
      and an increase in the percentage of BDNF-IR neurons in the DRG at 3 days after
      surgery compared to the group receiving saline injection. These findings suggest
      that in the lumbar disc herniation model, i.e. neuritis of the nerve root,
      increased NGF produced by the inflammatory responses in the dorsal root and DRG
      tissues may affect the production of BDNF in the DRG and may play important roles
      in the modulation of the dorsal horn neurons. These changes in neurotrophic
      factors in the primary afferents may be involved in the pathophysiological
      mechanisms of neuropathic pain produced by lumbar disc herniation.

PMID- 12237191
TI  - 5-HT2A receptor subtype in the peripheral branch of sensory fibers is involved in
      the potentiation of inflammatory pain in rats.
AB  - One of the major serotonin (5-HT) receptor subtypes expressed in the rat dorsal
      root ganglion (DRG) neurons is the 5-HT2A receptor. We have previously shown that
      5-HT2A receptors in the peripheral sensory terminals are responsible for 5-HT
      induced pain and hyperalgesia. In the present study, we characterized neurons
      expressing 5-HT2A receptors in the rat DRG neurons by means of in situ
      hybridization, immunohistochemistry, reverse transcription-polymerase chain
      reaction (RT-PCR) and behavioral tests. In situ hybridization on consecutive
      sections revealed that 5-HT2A receptor mRNA is colocalized with calcitonin-gene
      related peptide (CGRP) mRNA (100/104; 96.2%) but not with c-Ret mRNA (1/115;
      0.9%). Signals for 5-HT2A receptor mRNA were found in 9.4 +/- 2.2% of normal DRG
      (L5) neurons, most of which were small to medium in size. Four days of complete
      Freund's adjuvant-induced inflammation of the hindpaw doubled the incidence of 5
      HT2A receptor mRNA-expressing neurons to 19.3 +/- 2.8%. The level of 5-HT2A
      receptor mRNA in DRGs of normal and various pathological conditions was then
      determined by RT-PCR. The level was up-regulated by peripheral inflammation, but
      not by axotomy or chronic constriction of the peripheral nerve. Systemic
      administration of 5-HT2A receptor antagonist (Sarpogrelate HCI) produced
      analgesic effects on thermal hyperalgesia caused by peripheral inflammation, but
      failed to attenuate thermal hyperalgesia in chronic constriction injury model.
      These findings suggest that 5-HT2A receptors are mainly expressed in CGRP
      synthesizing small DRG neurons and may be involved in the potentiation of
      inflammatory pain in the periphery.

PMID- 12237192
TI  - Inward currents in primary nociceptive neurons of the rat and pain sensations in
      humans elicited by infrared diode laser pulses.
AB  - Radiant heat is often used to study nociception in vivo. We now used infrared
      radiation generated by a diode laser stimulator (wavelength 980 nm) to
      investigate transduction mechanisms for noxious heat stimuli in acutely
      dissociated dorsal root ganglion (DRG) neurons of rats in vitro. The laser
      stimulator offered the unique opportunity to test whether the same stimuli also
      elicit pain sensations in humans. A specific heat-induced current (I(heat)) was
      elicited in six of 13 small DRG neurons (diameter < or =30 microm) tested in the
      whole-cell configuration of the patch-clamp mode. Current responses in the seven
      heat-insensitive neurons were within the range explainable by the temperature
      dependence of the recording setup. I(heat) was characterized by: (1) non
      linearity of its amplitude during a suprathreshold heat ramp as well as with
      stimuli of increasing intensity with an estimated threshold of 42 +/- 1 degrees
      C; (2) fast rise time and even faster decay time (t(1/2) = 96.5 +/- 5.9 and 27.7
      +/- 1.5 ms, respectively); and (3) rate dependence of its induction. All three
      heat-sensitive neurons tested were also sensitive to capsaicin. The mean
      threshold for the induction of I(heat) was 2.8 +/- 0.3 J mm(-2). The threshold
      for the induction of action potentials by depolarizing current pulses was
      significantly reduced after laser stimulation, suggesting a sensitization at the
      transformation stage. No such change was seen in heat-insensitive neurons that
      underwent the same heat stimuli. The same diode laser elicited pain sensations
      and laser-evoked potentials in human subjects. No significant differences were
      seen between the pain thresholds in hairy and in glabrous skin, probably due to
      the deep penetration of this laser radiation. The mean pain threshold for stimuli
      > or =200 ms in humans was 2.5 +/- 0.2 J mm(-2) (n = 11), and did not differ from
      the thresholds for the induction of I(heat) in vitro. Our results indicate that
      I(heat) in primary sensory neurons can be activated by infrared laser pulses that
      are painful in humans.

PMID- 12237193
TI  - Systematic review of randomised controlled trials of psychological therapy for
      chronic pain in children and adolescents, with a subset meta-analysis of pain
      relief.
AB  - A systematic review and subset meta-analysis of published randomised controlled
      trials of psychological therapies for children and adolescents with chronic pain
      is reported. A search of four computerised abstracting services recovered 123
      papers from which 28 potential trials were identified. Eighteen met the criteria
      for inclusion in the review. The majority of these papers reported brief
      behavioural and cognitive behavioural interventions for children with headache
      and many were conducted in community (i.e. school) settings. Meta-analysis was
      applicable for 12 headache trials and one trial of recurrent abdominal pain using
      the Pain Index. The odds-ratio for a 50% reduction in pain was 9.62 and the
      number needed to treat was 2.32, indicating that the psychological treatments
      examined are effective in reducing the pain of headache. The quality of the 18
      trials retrieved is narratively reviewed and suggestions for the development of
      trials in this field are made.

PMID- 12237194
TI  - A mouse model of neuropathic cancer pain.
AB  - We developed a mouse model of neuropathic cancer pain by inoculating Meth A
      sarcoma cells to the immediate proximity of the sciatic nerve in BALB/c mice. The
      tumor grows predictably with time and gradually compresses the nerve, thereby
      causing nerve injury. Time courses of thermal hyperalgesia and mechanical
      sensitivity to von Frey hairs were determined and signs of spontaneous pain were
      evaluated. We compared this model with the chronic constriction injury (CCI)
      model, which is a neuropathic pain model widely utilized in the rat. Furthermore,
      to characterize the difference in nerve injury between the two models, we
      performed histological examination of the nerve of the two models by light and
      electron microscopy. Progressive compression of the sciatic nerve by growth of a
      tumor mass resulted in a gradual development of thermal hyperalgesia and
      mechanical allodynia in the ipsilateral hind paw. Signs of spontaneous pain, such
      as lifting of the paw, were also observed. However, further growth of the tumor
      reversed the mechanical hypersensitivity and produced mechanical hyposensitivity,
      while thermal hyperalgesia and signs of spontaneous pain still persisted.
      Histologically, gradual compression by the tumor resulted in a progressive damage
      to both myelinated and unmyelinated fibers. However, the severity of damage to
      the myelinated fibers was considerably less compared to that of the CCI mice. In
      the CCI mice, severe damage to myelinated fibers, especially large fibers, was
      observed and unmyelinated fibers were damaged to a lesser degree. These results
      suggest that gradual compression of a nerve by a malignant tumor results in nerve
      damage with a profile considerably different from that of chronic constriction
      injury produced by loose ligation of the nerve. Our new tumor model may be useful
      in studies of neuropathic cancer pain due to nerve compression by malignant
      tumors.

PMID- 12237195
TI  - Partial sciatic nerve ligation induces increase in the phosphorylation of
      extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) in
      astrocytes in the lumbar spinal dorsal horn and the gracile nucleus.
AB  - The activation of glial cells in the spinal dorsal horn and the gracile nucleus
      by inflammation and nerve injury has been suggested to be involved in neuronal
      plasticity and central sensitization, hence contributing to tactile allodynia.
      The aim of this study was to determine the possible intracellular signal
      transduction pathway associated with glial cells, which have been activated by
      partial sciatic nerve ligation (PSNL), a well-characterized rat model of
      neuropathic pain. At 3 weeks post-lesion, PSNL markedly increased glia fibrillary
      acidic protein (GFAP) immunoreactive (IR) astrocytes in both the L4-5 spinal
      dorsal horn and the gracile nucleus. Moreover, PSNL increased the phosphorylation
      of mitogen activated protein (MAP) kinases, including the extracellular signal
      regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not p38, in glia
      like cells in these same areas. Both phosphorylated (p) ERK- and JNK-IR cells
      were co-localized with GFAP, suggesting their expression in reactive astrocytes.
      In summary, our data indicate that PSNL activates ERK/MAP and JNK/MAP kinase
      pathways in astrocytes in the dorsal horn and the gracile nucleus, these events
      possibly being involved in the pathogenesis of neuropathic pain.

PMID- 12237196
TI  - Wound sensitivity as a measure of analgesic effects following surgery in human
      neonates and infants.
AB  - Postoperative wound sensitivity following abdominal surgery in neonates and
      infants has been little investigated, and is not well understood. Our aim was to
      quantify this sensitivity using the abdominal skin reflex (ASR), and to test the
      hypothesis that the threshold of this reflex would decrease following surgery,
      and would increase with the administration of analgesia. We measured ASR
      thresholds in infants under 1 year receiving unilateral abdominal surgery and in
      a small comparison group of non-surgical infants. The reflex was elicited by
      applying calibrated von Frey hairs to both sides of the abdomen at the same
      segmental level. In addition to threshold, the degree of reflex radiation as
      denoted by hip flexion was measured. The reflex threshold was significantly
      lowered at the wound site by up to 78% following surgery, and subsequently
      increased to varying degrees based on the type of analgesia used. The post
      surgical drop in threshold was accompanied by an increase in reflex radiation.
      Thresholds remained below pre-operative values 24 h after surgery on the operated
      side. In addition, it was observed that infants in whom the indication for
      surgery was a chronic condition, displayed lower threshold values on the affected
      side prior to surgery. An objective and quantitative measure has been developed
      of wound sensitivity and level of analgesia in infants following surgery. The
      reflex threshold also provides a means of quantifying human central sensory
      processing, and may be used to detect referred visceral hypersensitivity in this
      age group.

PMID- 12237197
TI  - Pain and negative emotions in the face: judgements by health care professionals.
AB  - Facial expression of pain has rarely been researched in the context of facial
      expression of negative emotions with which it may occur. The main aim of the
      study was to investigate how pain expression resembled or differed from that of
      other negative emotions (fear, anger, sadness, surprise, disgust and
      embarrassment), using multidimensional scaling, a dimensional approach to
      understanding relationships among emotions. As possible misidentification of
      facial expressions by participants could distort those results, a judgement study
      as a categorical approach was conducted to examine the accuracy of identification
      of pain and negative emotion facial expressions. The sample was health care
      professionals. Identification of pain was good (unbiased hit rate 58.8%), but
      less than all other negative emotions. Confidence in ratings approximated
      accuracy of identification. Multidimensional scaling revealed two dimensions: the
      first distinguished embarrassment from all other emotion expressions; the second
      separated pain, sadness and anger from fear, surprise and disgust. Possible
      explanations for these findings were sought in patterns of facial action units,
      and in the messages conveyed by the expressions according to Fridlund's
      Behavioural Ecology View.

PMID- 12237198
TI  - Naloxone increases pain induced by topical capsaicin in healthy human volunteers.
AB  - Opioid receptors occur in locations of strategic importance within the central
      nervous system for modulation of pain. Is pain reduced by ongoing inhibition
      mediated by activation of these receptors? Experiments to date in which the
      opioid-receptor antagonist, naloxone, is administered during a painful event have
      yielded unclear results. Topically applied capsaicin can be used to induce tonic
      pain of moderate to severe intensity without tissue injury and is an ideal
      stimulus for studying acute pain modulation. We therefore conducted a placebo
      controlled double-blind crossover study to investigate the effects of naloxone on
      capsaicin-induced pain (five men, four women, aged 29 +/- 5 years). Capsaicin
      (10%) was applied topically and subjects rated pain every 2 min. The subjects
      were told that any drug given to them could increase, decrease, or not change
      their pain sensation. Pain plateaued after 20 min. At 26 min subjects received
      either naloxone or placebo in double-blind fashion. At 56 min subjects received
      the alternative (placebo or naloxone). In a second session the order of
      presentation was reversed. The naloxone induced a significant increase in pain
      compared both to baseline (P < 0.01) and placebo (P < 0.01). The peak effect,
      reached at 12-20 min after naloxone delivery, was 59% greater than placebo. This
      experiment suggests that acute pain is actively suppressed by endogenous opioid
      receptor activation.

PMID- 12237199
TI  - Differential effects of spinal CNQX on two populations of dorsal horn neurons
      responding to colorectal distension in the rat.
AB  - The present study examined the effect of a spinally administered excitatory amino
      acid antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 1, 2.5, 5 microg) on
      responses of spinal dorsal horn neurons to graded intensities (20, 40, 60, 80
      mmHg) of colorectal distention (CRD). Extracellular single unit recordings were
      made from 28 dorsal horn neurons in the L6-S2 spinal cord. Neurons excited by CRD
      were subclassified as short latency abrupt (SLA) neurons and short latency
      sustained (SLS) neurons. The response to graded intensities of CRD was dose
      dependently attenuated in 9/17 SLA neurons (53%). The response to CRD was also
      dose-dependently attenuated in 8/11 SLS neurons (73%). The response to CRD in the
      remaining eight SLA neurons and three SLS neurons was not attenuated by CNQX.
      Comparing only neurons that were significantly attenuated by the CNQX, it was
      found that the magnitude of attenuation of the response to noxious CRD (80 mmHg)
      produced by 5 microg CNQX was significantly greater in SLA (63 +/-6%) vs. SLS (40
      +/- 6%) neurons. While CNQX produced a significant attenuation of the response to
      innocuous CRD (20 mmHg), there was no difference between the SLA and SLS neurons.
      The effects of CNQX on the response to somatic stimulation (touch, pinch) of the
      cutaneous receptive field of these 28 neurons were qualitatively examined in all
      neurons and quantitatively examined in nine neurons (five SLA and four SLS
      neurons). CNQX generally decreased the response to pinch or touch, even if CNQX
      did not attenuate the response to CRD. These results suggest that subpopulations
      of SLA and SLS neurons are differentially modulated by non-NMDA ionotropic
      excitatory amino acid receptors and that these neuronal subtypes contribute
      differently to visceral sensory processing. Furthermore, the lack of correlation
      between the effects of CNQX on visceral and somatic sensory processing in the
      same neuron underscores potential differences in processing of visceral and
      somatic pain.

PMID- 12237200
TI  - Anger and pain sensitivity in chronic low back pain patients and pain-free
      controls: the role of endogenous opioids.
AB  - The experience of anger (i.e. trait anger) and anger management style (i.e. anger
      in, anger-out) are related to sensitivity to acute and chronic pain stimuli,
      although underlying mechanisms are unknown. This study tested whether anger
      variables are associated with impaired endogenous opioid antinociceptive
      activity, and whether these relationships differed between chronic pain patients
      and healthy normals. Forty-three chronic low back pain (LBP) sufferers and 45
      pain-free normals received opioid blockade (8 mg naloxone i.v.) or placebo
      blockade (saline) in randomized, counterbalanced order in separate sessions.
      During each session, subjects participated in a 1-min finger pressure pain task
      followed by an ischemic forearm pain task (maximum duration 5 min), providing
      pain intensity ratings during and immediately following each task. As a measure
      of opioid antinociceptive function, drug effects were derived by subtracting
      placebo from blockade condition pain ratings. Multivariate general linear model
      analyses indicated that anger-out, but not anger-in, had significant main effects
      on both finger pressure drug effects (P < 0.05) and ischemic task drug effects (P
      < 0.05). As hypothesized, high anger-out scores were associated with an absence
      of opioid analgesia during the acute pain tasks; low anger-out scores were
      associated with effective opioid analgesia. A similar non-significant trend was
      noted for trait anger on finger pressure drug effects (P < 0.06). Anger-out x
      LBP/normal interactions were non-significant, suggesting that links between anger
      out and drug effects were similar for patients and normals. Controlling for
      depression did not eliminate the significant relationship between anger-out and
      drug effects. Findings suggest that anger-in and anger-out affect pain
      sensitivity through different mechanisms: only the effects of anger-out may be
      mediated by endogenous opioid dysfunction.

PMID- 12237201
TI  - Magnesium Bier's block for treatment of chronic limb pain: a randomised, double
      blind, cross-over study.
AB  - Magnesium is a physiological antagonist of both calcium and the NMDA receptor.
      Patients with chronic pain of a limb (>1 month's duration) were treated with two
      Bier's blocks (250 mmHg, 10 m) in a randomised, double-blind, cross-over design.
      They received once 20% magnesium sulphate (500 mg) + lignocaine 1% (75 mg), and
      once physiological saline + lignocaine 1% (75 mg). The volume of both treatments
      was 10 ml. Efficacy data from 49 treatments (25 magnesium, 24 placebo) could be
      analysed. With magnesium-lignocaine, the duration of pain relief as reported by
      the patients was on average 23 days (95% CI 8-38) compared with 6 days (95% CI 2
      10) with lignocaine alone (P = 0.043). With magnesium-lignocaine, 54.2% of
      patients had more than 50% pain relief compared with 25% with lignocaine alone
      (number-needed-to-treat 3.5, P = 0.075). With magnesium-lignocaine, 20% of
      patients had a treatment failure (i.e. pain relief <24 h) compared with 50% with
      lignocaine alone (number needed-to-treat 3.3, 95% CI 1.8-29, P = 0.038). The
      magnesium-lignocaine treatment was painful in 52% of patients compared with 8%
      with lignocaine alone (number-needed-to-harm 2.3, 95% CI 1.5-4.5, P =0.0008). For
      patients with chronic limb pain, the addition of magnesium to a Bier's block with
      lignocaine improves and prolongs pain relief and reduces the number of treatment
      failures. The optimal dose of lignocaine to prevent magnesium-induced aching of
      the treated limb needs to be established. Bier's block with magnesium-lignocaine
      may provide a possible treatment alternative in these patients.

PMID- 12237202
TI  - Response of neurons in the thalamic nucleus submedius (Sm) to noxious stimulation
      and electrophysiological identification of on- and off-cells in rats.
AB  - Previous studies have indicated that thalamic nucleus submedius (Sm) is involved
      in nociceptive modulation and plays an important role in an endogenous analgesic
      system (a feedback loop) consisting of spinal cord (Sc)-Sm-ventrolateral orbital
      cortex-periaqueductal gray-Sc. However, the function of different types of Sm
      neurons in nociceptive modulation is unclear. For this reason, on the basis of
      further studies of properties of the Sm neurons responding to noxious stimuli,
      the different effects of systemic morphine on the Sm neurons were examined and
      two classes of nociceptive modulatory neurons, named as off- and on-cells, in
      this region were identified in lightly anesthetized rats. The results showed that
      (1) most (84%, 132/157) of the Sm neurons responded to peripheral noxious
      stimuli. Of these neurons, 66% (n = 87) were inhibited, 34% (n = 45) excited. All
      neurons had very large and bilateral, even all body receptive fields. No neuron
      was found to be responsive to innocuous stimulation; (2) systemic morphine
      increased the firing rate of neurons inhibited by noxious stimulation, but
      decreased that of neurons excited by the same stimulation. Furthermore, the
      effects of morphine could be reversed by systemic naloxone; (3) 45 of Sm neurons
      examined could be divided into three different classes: off-cells that decreased
      the firing rate from tail heating just prior to occurrence of the tail-flick (TF)
      reflex (3140 +/- 167 ms, n = 27), on-cells that increased the firing rate just
      before the TF reflex (1720 +/- 240 ms, n = 8), and neutral-cells that did not
      respond to any stimuli and neuronal activities were not related to the TF reflex
      (n = 10). Findings of this study provided electrophysiological evidence for
      involvement of Sm neurons, as those in the rostral ventromedial medulla, in the
      opioid-receptor-mediated descending nociceptive modulation.

PMID- 12237203
TI  - Sensory stimulation (TENS): effects of parameter manipulation on mechanical pain
      thresholds in healthy human subjects.
AB  - Transcutaneous electrical nerve stimulation (TENS) is a popular form of
      electrostimulation. Despite an extensive research base, there remains no
      consensus regarding the parameter selection required to achieve maximal
      hypoalgesic effects. The aim of this double blind, sham-controlled study was to
      investigate the relative hypoalgesic effects of different TENS parameters
      (frequency, intensity and stimulation site) upon experimentally induced
      mechanical pain. Two hundred and forty participants were recruited in order to
      provide statistical analysis with 80% power at alpha = 0.05. Subjects were
      randomised to one of the six TENS groups, a control, and a sham TENS group (n =
      30, 15 males, 15 females, per group). TENS groups differed in their combinations
      of stimulation; frequency (4 or 110 Hz), intensity ('to tolerance' or 'strong but
      comfortable') and stimulation site (segmental--over the distribution of the
      radial nerve or, extrasegmental--over acupuncture point 'gall bladder 34', or a
      combination of both segmental and extrasegmental). Pulse duration was fixed at
      200 micros. Stimulation was delivered for 30 min and subjects were then monitored
      for a further 30 min. Mechanical pain threshold (MPT) was measured using a
      pressure algometer and taken from the first dorsal interosseous muscle of the
      dominant hand, ipsilateral to the stimulation site. MPT measures were taken, at
      baseline, and at 10-min intervals for 60 min. Difference scores were analysed
      using repeated measures and one-way ANOVA and relevant post hoc tests. Low
      frequency, high intensity, extrasegmental stimulation produced a rapid onset
      hypoalgesic effect, which increased during the stimulation period (P < 0.0005
      control and sham) and was sustained for 30 min post-stimulation (P <
      0.0005(control), P = 0.024(sham)). Whilst high frequency, 'strong but
      comfortable' intensity, segmental stimulation produced comparable hypoalgesic
      levels during stimulation, this effect was not sustained post-stimulation.
      Stimulation at a combination of the two sites did not produce any greater
      hypoalgesic effects. These results may have implications for the clinical use of
      sensory stimulation.

PMID- 12237204
TI  - No detectable analgesic effects in the formalin test even with one million bovine
      adrenal chromaffin cells.
AB  - The present experiments were conducted to identify analgesic agents for
      transfection into immortalized adrenal chromaffin cell lines to maximize their
      analgesic potential. Analgesic agents known to be produced by adrenal chromaffin
      cells were infused intrathecally at a low dose (0.2 microg) which might
      conceivably be attained by adrenal chromaffin cell transplants. Numerous agents,
      administered individually and in two-factor combinations, produced significant
      analgesic effects in the formalin test. Before assessing the potential additive
      or synergistic effects of these analgesic agents with adrenal chromaffin cells,
      studies were conducted to demonstrate analgesic effects with adrenal chromaffin
      cells alone. Analgesic effects were previously reported in the literature with 80
      100k intrathecal bovine adrenal chromaffin (BAC) cells; but in the present study
      500k purified BAC cells failed to produce detectable analgesic effects. One
      million purified BAC cells also failed to produce analgesic effects in the
      formalin test. In a final study, even nicotine-stimulated release from one
      million purified BAC cells failed to produce analgesic effects in the formalin
      test. The fact that even one million nicotine-stimulated BAC cells failed to
      demonstrate therapeutic potential in these blinded experiments under conditions
      which were clearly sensitive to the analgesic agents produced by BAC cells,
      raises serious questions about the clinical utility of this experimental
      treatment.

PMID- 12237205
TI  - Dopamine D2 receptor binding in the human brain is associated with the response
      to painful stimulation and pain modulatory capacity.
AB  - The pain modulatory role of dopamine D2 receptors of the human forebrain was
      studied by determining the association between dopamine D2 receptor binding
      potential and the response to experimental pain. Nineteen healthy male volunteers
      participated in a dopamine D2 receptor positron emission tomography study. The
      extrastriatal regions of interest studied with [11C]FLB 457 as radioligand (n =
      11) were the anterior cingulum, the medial and lateral thalamus, the medial and
      lateral frontal cortex, and the medial and lateral temporal cortex. The striatal
      regions of interest studied with [11C]raclopride (n = 8) were the caudate nucleus
      and the putamen. The latency to the ice water-induced cold pain threshold and
      tolerance were determined in a separate psychophysical test session. Moreover,
      the cutaneous heat pain threshold and its elevation by concurrent cold pain in
      the contralateral hand were determined in each subject. Cold pain threshold was
      inversely correlated with D2 binding potential in the right putamen and the cold
      pain tolerance was inversely correlated with D2 binding potential in the right
      medial temporal cortex. The magnitude of heat pain threshold elevation induced by
      concurrent cold pain was directly correlated with D2 binding potential in the
      left putamen. Other correlations of D2 binding potentials in varying brain
      regions with sensory responses were not significant. A psychophysical control
      study (n = 10) showed that cold pain responses were identical in the right and
      left hand. The results indicate that dopamine D2 receptor binding potential in
      the human forebrain, particularly in the striatum, may be an important parameter
      in determining the individual cold pain response and the potential for central
      pain modulation. Accordingly, an individual with only few available D2 receptors
      in the forebrain is likely to have a high tonic level of pain suppression,
      combined with a low capacity to recruit more (dopaminergic) central pain
      inhibition by noxious conditioning stimulation.

PMID- 12237206
TI  - Pain in children with cerebral palsy: common triggers and expressive behaviors.
AB  - To obtain parents' identification and description of the behaviors, health care
      procedures and daily living situations associated with pain in children with
      cerebral palsy (CP), surveys were sent to parents of children with CP recruited
      via a clinic case list and a parents' newsletter. Forty-three parents completed
      the survey. Results indicated that children's ability to communicate pain
      verbally did not influence whether or not their parent reported observing pain.
      Most children (67%) were reported to have displayed pain within the month prior
      to rating. All pain behaviors on the Non-Communicating Children's Pain Checklist
      (Dev Med Child Neurol 40 (1998) 340) were endorsed by some parents, and few
      additional pain behaviors were identified, suggesting that this instrument
      adequately samples the pain behavior of children with CP. Assisted stretching was
      the daily living activity most frequently identified as painful by parents (93%
      of those reporting pain), and the one with the highest mean pain intensity.
      Needle injection (40%) was the medical and nursing procedure most frequently
      identified by parents as painful for their children. Range of motion manipulation
      was the therapy most frequently identified as painful by parents (58%), and the
      one with the highest mean intensity. Parents are able to observe pain in their
      children with CP regardless of the child's verbal fluency. Knowledge of behaviors
      and painful situations identified by parents can facilitate management of pain in
      children with CP.

PMID- 12237207
TI  - A confirmatory factor analysis of the Beck Depression Inventory in chronic pain.
AB  - The Beck Depression Inventory (BDI) is widely used to assess depression in
      chronic pain despite doubts about its structure and therefore its interpretation.
      This study used a large sample of 1947 patients entering chronic pain management
      to establish the structure of the BDI. The sample was randomly divided to conduct
      separate exploratory (EFA) and confirmatory factor analyses (CFA). EFA produced
      many satisfactory two-factor solutions. The series of CFA generated showed
      reasonable fit for ten of those solutions. All included a first factor identified
      as negative view of the self (items: failure, guilt, self-blame, self-dislike,
      punishment and body image change), and a second factor identified as somatic and
      physical function (items: work difficulty, loss of appetite, loss of libido,
      fatigability, insomnia and somatic preoccupation). The remaining items (suicidal
      ideation, social withdrawal, dissatisfaction, sadness, pessimism, crying,
      indecisiveness, weight loss, irritability) loaded infrequently or not at all in
      the CFA solutions. They did not form a coherent factor but comprised items
      associated with negative affect. When compared with published data from samples
      of depressed patients drawn from mental health settings the mean item scores for
      items reflecting the negative view of the self were consistently statistically
      lower that that observed in samples; there was no consistent difference between
      the samples on the items reflecting somatic and physical function; but the mean
      scores for the remaining affect items were significantly greater in the mental
      health samples. This version of depression is strikingly different from the
      psychiatric model of depression (e.g. DSM-IV or ICD-10), which is primarily
      defined by affective disturbance, and secondarily supported by cognitive and
      somatic symptoms. The finding is consistent with a reconsideration of what
      constitutes depression in the presence of chronic pain. It also has important
      clinical implications: it may provide a way to distinguish depressed patients
      with typical cognitive biases, who require specific treatment for depression
      alongside pain management.

PMID- 12237208
TI  - The course of chronic pain in the community: results of a 4-year follow-up study.
AB  - Little is known about the course of chronic pain in the community. Such
      information is needed for the prevention and management of chronic pain. We
      undertook a 4-year follow-up study of 2184 individuals living in Grampian, UK to
      describe patterns and predictors of change in chronic pain over time. In October
      2000, participants completed a postal questionnaire including case definition
      questions, the chronic pain grade questionnaire, the SF-36 and socio-demographic
      questions. Information from this questionnaire was compared to information
      collected from a similar questionnaire in 1996. A response rate of 83% was
      achieved for the follow-up study. The overall prevalence of chronic pain (pain or
      discomfort present either all the time or on and off for 3 months or longer)
      increased from 45.5% at baseline to 53.8% at follow-up. Seventy-nine percent of
      those with chronic pain at baseline still had it at follow-up. The average annual
      incidence was 8.3% and the average annual recovery rate was 5.4%. Individuals in
      the study samples who are in lowest quartile of SF-36 domains--physical
      functioning, social functioning and bodily pain at baseline--were more likely to
      develop chronic pain at follow-up, and respondents who were retired were less
      likely to develop chronic pain. Individuals in the study samples in the lowest
      quartile of SF-36 domains, bodily pain and general health at baseline, were less
      likely to recover from their chronic pain, as were those aged 45-74 compared with
      those aged 25-34. We concluded that chronic pain is a common, persistent problem
      in the community with relatively high incidence and low recovery rates. The lack
      of association between onset or recovery from chronic pain and most traditional
      socio-demographic factors, highlights the need to broaden the range of factors
      included in studies of chronic pain aetiology.

PMID- 12237209
TI  - Pain in traumatic upper limb amputees in Sierra Leone.
AB  - Data on 40 upper limb amputees (11 bilateral) with regard to stump pain, phantom
      sensation and phantom pain is presented. All the patients lost their limbs as a
      result of violent injuries intended to terrorise the population and were assessed
      10-48 months after the injury. All amputees reported stump pain in the month
      prior to interview and ten of the 11 bilateral amputees had bilateral pain.
      Phantom sensation was common (92.5%), but phantom pain was only present in 32.5%
      of amputees. Problems in translation and explanation may have influenced the low
      incidence of phantom pain and high incidence of stump pain. In the bilateral
      amputees phantom sensation, phantom pain and telescoping all showed bilateral
      concordance, whereas stump pain and neuromas did not show concordance. About half
      the subjects (56%) had lost their limb at the time of injury (primary) while the
      remainder had an injury, then a subsequent amputation in hospital (secondary).
      There was no association between the incidence of phantom pain and amputation
      irrespective of being primary or secondary.

PMID- 12237210
TI  - Subcortical structures involved in pain processing: evidence from single-trial
      fMRI.
AB  - Pain is processed in multiple cortical and subcortical brain areas. Subcortical
      structures are substantially involved in different processes that are closely
      linked to pain processing, e.g. motor preparation, autonomic responses, affective
      components and learning. However, it is unclear to which extent nociceptive
      information is relayed to and processed in subcortical structures. We used single
      trial functional magnetic resonance imaging (fMRI) to identify subcortical
      regions displaying hemodynamic responses to painful stimulation. Thulium-YAG
      (yttrium-aluminum-granate) laser evoked pain stimuli, which have no concomitant
      tactile component, were applied to either hand of healthy volunteers in a
      randomized order. This procedure allowed identification of areas displaying
      differential fMRI responses to right- and left-sided stimuli. Hippocampal
      complex, amygdala, red nucleus, brainstem and cerebellum were activated in
      response to painful stimuli. Structures related to the affective processing of
      pain showed bilateral activation, whereas structures involved in the generation
      of withdrawal behavior, namely red nucleus, putamen and cerebellum displayed
      differential (i.e. asymmetric) responses according to the side of stimulation.
      This suggests that spatial information about the nociceptive stimulus is made
      available in these structures for the guidance of defensive and withdrawal
      behavior.

PMID- 12237211
TI  - Assessment of the reproducibility of intradermal administration of capsaicin as a
      model for inducing human pain.
AB  - The reproducibility and tolerability of intradermal (i.d.) administration of
      capsaicin as a method for eliciting human pain was assessed in healthy male
      volunteers (n = 12). The primary endpoints for assessing pain were spontaneous
      pain response and areas of allodynia, pinprick hyperalgesia and neurogenic
      inflammation. These were recorded before, immediately after, and at regular
      intervals following each of four doses (250 microg) of capsaicin (two per trial
      day). Within- and between-subject variability to the technique was assessed by
      measuring the maximum recorded values (max), time to maximum value (t(max)) and
      area under the curve (AUC(0-1 h)) of each of the endpoints. Tolerability to the
      technique was addressed by recording adverse events. Reproducibility of the i.d.
      capsaicin model was demonstrated for each type of capsaicin-induced pain.
      Following each dose, the magnitude and profile of response and overall AUC values
      were similar for each parameter although some decrease in pinprick hyperalgesia
      was observed over time. For spontaneous pain, evidence of a period effect was
      observed in mean AUC data, with values increasing following the second dose of
      each trial day. This effect was confounded by the possibility of an arm effect,
      with the non-dominant arm appearing to be more sensitive to pain than the
      dominant arm. The data were not sufficient to confirm the existence of these
      effects. Between-subject variability and within-day, within-subject variability
      accounted for most of the variability observed in the trial. By optimising study
      design to eliminate these sources of variability, it was estimated that
      spontaneous pain and the area of allodynia would be the least variable endpoints.
      A positive correlation was found between the area of allodynia and area of
      pinprick hyperalgesia (r(2) = 0.835). Overall, the model was well tolerated with
      no reports of adverse events. We conclude that the tolerability profile, and
      variability of i.d. capsaicin-induced pain is acceptable for pharmacological
      profiling of novel anti-nociceptive agents, with limited number of subjects.

PMID- 12237212
TI  - Micromolar lidocaine selectively blocks propagating ectopic impulses at a
      distance from their site of origin.
AB  - Abnormal impulses caused by very slowly inactivating Na channels of peripheral
      nerve have been proposed to play a critical role in neuropathic pain. Low
      concentrations of local anesthetics, often effective in treating experimental and
      clinical neuropathic pain, are also known to potently suppress the long after
      depolarizations induced by these persistently open Na channels. However, these
      drug actions on impulses that have propagated away from such sites are
      undetermined. In the present study, the focal application of anemone toxin II
      (ATX, 300 nM), which slows Na-channel inactivation, produced prolonged
      depolarizing after-potentials and, coincidentally, induced spontaneous bursting
      impulse activity that propagated away from the site of ATX application in the
      frog sciatic nerve in vitro. The application of low concentrations of lidocaine
      (1-10 microM), both at the site of ATX exposure and at a distant site,
      selectively and reversibly inhibited the spontaneous bursting, while having no
      effect on the electrically stimulated initial spike of the compound action
      potential. Inhibition occurred as a shortening of burst episodes rather than a
      reduction in frequency of impulses within a burst or a reduction of intraburst
      impulse amplitude. Tetrodotoxin also inhibited the induced spontaneous activity,
      but only at concentrations that also depressed the compound action potential
      spike. These findings show that low concentrations of lidocaine can restore
      normal firing patterns in nerve where hyperexcitability has been caused by
      delayed Na-channel inactivation, without acting directly at the site where
      ectopic impulses are generated. Thus, it appears that the pattern of abnormal
      activity rather than an abnormally gating Na channel per se can be a target for
      lidocaine's therapeutic action.

PMID- 12237213
TI  - Comparative study of electronic vs. paper VAS ratings: a randomized, crossover
      trial using healthy volunteers.
AB  - The visual analogue scale (VAS) is an established, validated, self-report measure
      usually consisting of a 10 cm line on paper with verbal anchors labeling the
      ends. Palmtop computers (PTCs also known as personal digital appliances) have
      incorporated VAS entry by use of a touch screen. However, the validity and
      psychophysical properties of the electronic VAS have never been formally compared
      with the conventional paper VAS. The aim of this study is to determine the
      agreement between the electronic (eVAS) and paper (pVAS) modes. Twenty-four
      healthy volunteers were recruited for this study. Each study participant provided
      input using both measurement methods by marking the eVAS and pVAS in response to
      two kinds of stimuli, cognitive and sensory. A verbal rating scale of seven
      descriptors of intensity represented the cognitive stimuli. Participants were
      asked to mark the location that best corresponded to the pain intensity described
      by each word on scales from 'no pain' to 'worst possible pain'. The sensory
      stimuli used were a set of test weights consisting of plastic containers ranging
      from 7 to 129 g. The VAS for sensory stimuli ranged from 0 (no weight) to
      'reference weight' (the heaviest weight outside the range of test weights). There
      were two types of input stimuli and two modes for recording responses for a total
      of four experimental conditions. Two evaluators independently measured and
      recorded all the pVAS forms to the nearest millimeter. A total of 2016 stimuli
      were rated. The overall correlation for ratings of both sensory and cognitive
      stimuli on eVAS and pVAS was r = 0.91. For paired verbal stimuli the correlation
      was r = 0.97. For paired sensory stimuli the correlation was r = 0.86. The
      correlation between group eVAS and pVAS ratings to common verbal stimuli was r =
      0.99. For common sensory stimuli the group correlation was r = 0.99. The median
      of correlations comparing eVAS and pVAS ratings was 0.99 for verbal stimuli and
      0.98 for sensory stimuli. Multivariate analyses showed equivalent stimuli to be
      rated much the same whether entered on paper VAS or PTC touch screen VAS (P <
      0.0001). Support was found for the validity of the computer version of the VAS
      scale.

PMID- 12237214
TI  - Psychometric properties of the non-communicating children's pain checklist
      revised.
AB  - The non-communicating children's pain checklist (NCCPC) has displayed preliminary
      validity and reliability for measuring pain in children with severe cognitive
      impairments (Dev Med Child Neurol 42 (2000) 609). This study provides evidence of
      the psychometric properties of a revised NCCPC (NCCPC-R) with a larger cohort of
      children. Caregivers of 71 children with severe cognitive impairments (aged 3-18)
      conducted observations of their children using the NCCPC-R during a time of pain
      and a time without pain. Fifty-five caregivers completed a second set of
      observations. The score results on the NCCPC-R were: internally consistent,
      significantly related to pain intensity ratings provided by caregivers,
      consistent over time, sensitive to pain, and specific to pain. Analyses of
      children's individual scores indicated up to 95% of their scores were consistent.
      Receiver operating characteristic curves suggest a score of 7 or greater on the
      NCCPC-R as indicative of pain in children with cognitive impairments, with 84%
      sensitivity and up to 77% specificity. These results provide evidence of NCCPC-R
      having excellent psychometric properties.

PMID- 12237215
TI  - Reduced basal release of serotonin from the ventrobasal thalamus of the rat in a
      model of neuropathic pain.
AB  - Drugs that inhibit reuptake of monoamines are frequently used to treat pain
      syndromes, e.g. neuropathy or fibromyalgia, where mechanical allodynia is
      present. Several lines of evidence suggest the involvement of supraspinal sites
      of action of these drugs. However, a direct study of supraspinal serotonin (5-HT)
      or norepinephrine (NE) release in an animal model in which allodynia is
      expressed, e.g. neuropathy, has not been done. The ventrobasal (VB) thalamus and
      the hypothalamus are major supraspinal projection regions for spinal neurons that
      transmit nociceptive information and are innervated by monoaminergic fibers. This
      study determined if peripheral neuropathy would induce changes in extracellular
      monoamines in VB thalamus and hypothalamus. Male Sprague-Dawley rats had spinal
      nerve roots L5 and L6 tightly ligated (neuropathic rats; NP) or sham (SHAM)
      surgery; contralateral and ipsilateral VB thalamus and contralateral hypothalamus
      were dialyzed with modified artificial cerebral spinal fluid (aCSF), with and
      without fluoxetine. NP rats had significantly decreased 5-HT content in
      dialysates of the contralateral VB thalamus compared with SHAM rats with (82%
      decrease) or without (63% decrease) fluoxetine in the perfusion medium over the
      180 min of the study. There were no differences in the ipsilateral VB thalamus.
      In contrast, release of 5-HT was unchanged in the hypothalamic dialysates of SHAM
      vs. NP rats. NE release was not different in dialysates of either the VB thalamus
      or hypothalamus of SHAM vs. NP rats. Synthesis of 5-HT, as assessed by
      accumulation of 5-hydroxytrytophan after treatment with an L-amino acid
      decarboxylase inhibitor, was not different between NP and SHAM rats in VB
      thalamic and hypothalamic brain tissue. This study is the first to demonstrate
      changes in monoamine release supraspinally in NP rats. The differential effect
      between VB thalamus and hypothalamus suggests that a terminal field change may be
      involved. Putative mechanisms for mediating this change include alterations of
      GABA-ergic systems and/or plasticity related to alterations in N-methyl-D
      aspartate receptor activation and nitric oxide release related to afferent
      hyperactivity induced by neuropathic pain.

PMID- 12237216
TI  - Pain catastrophizing and general health status in a large Dutch community sample.
AB  - The aim of the present study was to examine the association between pain
      catastrophizing and general health status in a Dutch adult community sample,
      including various subgroups of people with musculoskeletal pain in the analyses.
      For exploratory reasons this study partly replicated previous studies of the
      factor structure, reliability, and validity of the Pain Catastrophizing Scale
      (PCS). Results demonstrated that across different pain subgroups, catastrophizing
      uniquely contributed variance to the prediction of the various aspects of general
      health status beyond the variance explained by pain intensity, age, gender, and
      chronicity. Across subgroups strongest associations were found between
      catastrophizing and mental health, general health perception, social functioning,
      and vitality. Furthermore, the association between catastrophizing and the
      various aspects of general health status was not moderated by the chronicity of
      the pain. Results of the confirmatory factor analysis statistically confirmed a
      three-factor model of the PCS, which was invariant across different subgroups of
      people with musculoskeletal pain. Inter-factor correlations were high, and the
      incremental explanatory power of the three-factor model over that of a one-factor
      model was only marginal. This implies that a one-factor model might be
      justifiable as well, at least in the general community. Across various pain
      subgroups the reliability of the PCS total and subscales was adequate. Additional
      evidence for the concurrent validity of the PCS was found as well.

PMID- 12237217
TI  - Thermophilic cytochrome P450 (CYP119) from Sulfolobus solfataricus: high
      resolution structure and functional properties.
AB  - Crystal structures of a thermostable cytochrome P450 (CYP119) and a site-directed
      mutant, (Phe24Leu), from the acidothermophilic archaea Sulfolobus solfataricus
      were determined at 1.5-2.0 A resolution. We identify important crystallographic
      waters in the ferric heme pocket, observe protein conformational changes upon
      inhibitor binding, and detect a unique distribution of surface charge not found
      in other P450s. An analysis of factors contributing to thermostability of CYP119
      of these high resolution structures shows an apparent increase in clustering of
      aromatic residues and optimum stacking. The contribution of aromatic stacking was
      investigated further with the mutant crystal structure and differential scanning
      calorimetry.

PMID- 12237218
TI  - Modelling human cytochromes P450 involved in drug metabolism from the CYP2C5
      crystallographic template.
AB  - A historical background to homology modelling of human P450s involved in drug
      metabolism is outlined, showing that the progress in crystallographic studies of
      bacterial forms of enzyme and, latterly, determination of a mammalian P450
      crystal structure, has enabled the production of increasingly satisfactory models
      of human P450 enzymes. The methodology for the generation of P450 models by
      homology with crystallographic template structures is summarized, and recent
      results of CYP2C5-constructed models of P450s are described. These indicate that
      selective substrates are able to fit within the putative active sites of each
      enzyme, where key contacts with complementary amino acid residues are largely
      consistent with the results of site-directed mutagenesis experiments and
      metabolic studies. Consequently, the CYP2C5 crystal structure can be regarded at
      the current paradigm for homology modelling of the drug metabolizing P450s,
      especially those from the CYP2 family.

PMID- 12237219
TI  - Catalytically functional flavocytochrome chimeras of P450 BM3 and nitric oxide
      synthase.
AB  - P450 BM3 and the nitric oxide synthases are related classes of flavocytochrome
      mono-oxygenase enzymes, containing NADPH-dependent FAD- and FMN-containing
      oxidoreductase modules fused to heme b-containing oxygenase domains. Domain-swap
      hybrids of these two multi-domain enzymes were created by genetic engineering of
      different segments of reductase and heme domains from neuronal nitric oxide
      synthase and P450 BM3, as a means of investigating the catalytic competence and
      substrate-binding properties of the fusions and the influence of
      tetrahydrpbiopterin and calmodulin binding regions on the electron transfer
      kinetics of the chimeras. Despite marked differences in hybrid stability and
      solubility, four catalytically functional chimeras were created that retained
      good reductase activity and which could be expressed successfully in Escherichia
      coli and purified. All of the BM3 reductase domain chimeras (chimeras I-III)
      exhibited inefficient flavin-to-heme inter-domain electron transfer, diminishing
      their oxygenase activity. However, the chimera containing the neuronal nitric
      oxide synthase reductase domain (chimera IV) showed good oxygenase domain
      activity, indicating that the flavin-to-heme electron transfer reaction is
      relatively efficient in this case. The data reinforce the importance of the
      nature of inter-domain linker constitution in multi-domain enzymes, and the
      difficulties posed in attempts to create chimeric enzymes with enhanced catalytic
      properties.

PMID- 12237220
TI  - Expression, purification and spectroscopic characterization of the cytochrome
      P450 CYP121 from Mycobacterium tuberculosis.
AB  - The CYP121 gene from the pathogenic bacterium Mycobacterium tuberculosis has been
      cloned and expressed in Escherichia coli, and the protein purified to homogeneity
      by ion exchange and hydrophobic interaction chromatography. The CYP121 gene
      encodes a cytochrome P450 enzyme (CYP121) that displays typical electronic
      absorption features for a member of this superfamily of hemoproteins (major Soret
      absorption band at 416.5 nm with alpha and beta bands at 565 and 538 nm,
      respectively, in the oxidized form) and which binds carbon monoxide to give the
      characteristic Soret band shift to 448 nm. Resonance Raman, EPR and MCD spectra
      show the protein to be predominantly low-spin and to have a typical cysteinate-
      and water-ligated b-type heme iron. CD spectra in the far UV region describe a
      mainly alpha helical conformation, but the visible CD spectrum shows a band of
      positive sign in the Soret region, distinct from spectra for other P450s
      recognized thus far. CYP121 binds very tightly to a range of azole antifungal
      drugs (e.g. clotrimazole, miconazole), suggesting that it may represent a novel
      target for these antibiotics in the M. tuberculosis pathogen.

PMID- 12237222
TI  - The 'push' effect of the thiolate ligand in cytochrome P450: a theoretical
      gauging.
AB  - The 'push' effect of the thiolate ligand in cytochrome P450 is investigated using
      density functional calculations. Theory supports Dawson's postulate that the
      'push' effect is crucial for the heterolytic O-O bond cleavage of ferric
      peroxide, as well as for controlling the Fe(III)/Fe(II) redox process and gating
      the catalytic cycle. Two energetic factors that contribute to the 'push' effect
      are revealed. The dominant one is the field factor (DeltaE(field)=54-103
      kcal/mol) that accounts for the classical electrostatic repulsion with the
      negative charge of thiolate. The smaller factor is a quantum mechanical effect
      (DeltaE(QM)(sigma)=39 kcal/mol, DeltaE(QM)(pi)=4 kcal/mol), which is associated
      with the sigma- and pi-donor capabilities of thiolate. The effects of ligand
      replacement, changes in hydrogen bonding and dielectric screening are discussed
      in term of these quantities. In an environment with a dielectric constant of 5.7,
      the total 'push' effect is reduced to 29-33 kcal/mol. Manifestations of the
      'push' effect on other properties of thiolate enzymes are discussed.

PMID- 12237221
TI  - Replacement of active-site cysteine-436 by serine converts cytochrome P450 2B4
      into an NADPH oxidase with negligible monooxygenase activity.
AB  - The function of the unique axial thiolate ligand of cytochrome P450 has been
      investigated by mutagenesis of the active-site cysteine with other amino acids in
      NH(2)-truncated P450s 2B4 and 2E1. The expressed Ser-436 variant of P450 2B4 was
      highly purified but incurred considerable heme loss. The pyridine hemochrome
      spectrum of C436S is characteristic of protoporphyrin IX, and the absolute
      spectra display Soret maxima at 405 nm (ferric), 422 nm (ferrous), and 413 nm
      (ferrous CO). 2B4:C436S catalyzes the NADPH- and time-dependent formation of
      H(2)O(2) in the reconstituted enzyme system, with maximal rates at approximately
      equimolar amounts of P450 reductase and C436S hemeprotein. The 2-electron oxidase
      activity with saturating reductase is directly proportional to the concentration
      of 2B4:C436S, and the turnover is 60-70% of that of the wild-type enzyme. In
      contrast, the C436S variant is devoid of oxygenase activity with typical
      substrates such as d-benzphetamine, 1-phenylethanol, and 4-fluorophenol, and has
      only marginal 4-nitrophenol aromatic hydroxylation activity. H(2)O(2)-supported
      peroxidation of guaiacol and pyrogallol is comparable with 2B4 and mutant C436S
      and negligible relative to the turnover of peroxidases with these substrates.
      Neither 2B4 nor 2B4:C436S catalyzes H(2)O(2) decomposition. It is concluded that
      replacement of active-site Cys-436 by Ser converts P450 2B4 mainly into a 2
      electron oxidase.

PMID- 12237223
TI  - Oxidation and electronic state dependence of proton transfer in the enzymatic
      cycle of cytochrome P450eryF.
AB  - Hydrogen bond networks, consisting of hydrogen bonded waters anchored by
      polar/acidic amino acid sidechains, are often present in the vicinity of the
      oxygen binding clefts of P450s. Density functional and quantum dynamics
      calculations of a O(2) binding cleft network model of cytochrome
      P450eryF(CYP107A1) indicate that such structural motifs facilitate ultrafast
      proton transfer from network waters to the dioxygen of the reduced oxyferrous
      species via a multiple proton translocation mechanism with barriers of 7-10
      kcal/mol on its doublet ground state, and that the energies of the proton
      transfer reactant and constrained proton transfer products have an electronic and
      oxidation state dependence [J. Am. Chem. Soc. 124 (2002) 1430]. In the present
      study, the origin of the oxidation state dependence is shown to have its roots in
      differential proton affinities while the electronic state dependence of the
      reduced oxyferrous heme has its origins in subtle differences in network
      topologies near the transition state of the initial proton transfer event.
      Relaxed potential surface scans and unconstrained proton transfer product
      optimizations indicate that the proton transfer product in both the singlet
      oxyferrous heme and the reduced oxyferrous heme species in a quartet state are
      not viable stable (bound) states relative to the reactant form. While the proton
      affinity of H(3)O(+) is sufficient for it to protonate both the oxyferrous and
      the reduced oxyferrous heme species, hydrogen bond network stabilized water is
      only capable of protonating the reduced oxyferrous form. This interpretation is
      substantiated by study of the NO bound reduced ferrous heme of P450nor, which is
      isoelectronic with the oxyferrous heme and has a similar proton affinity. Density
      functional calculations on a more extensive O(2) binding cleft model support the
      multiple proton translocation mechanism of transfer but indicates that the
      significant negative charge density on the bound dioxygen of the reduced
      oxyferrous heme species, in its doublet ground state, polarizes the associated
      hydrogen bond network sufficiently so as to result in short, strong, low-barrier
      hydrogen bonds. The computed O-H-O bond distances are less than 2.55 A and have a
      near degeneracy of the proton transfer reactant and initial (sudden) proton
      transfer products. These low-barrier hydrogen bond features, in addition to the
      finding of a (zero point uncorrected) barrier of 1.3 kcal/mol, indicate that
      proton transfer from water to the distal oxygen should be rapid, facile and may
      not require large curvature tunneling as originally suggested by use of a smaller
      model. An initial assessment of protonation of the reduced oxyferrous heme distal
      oxygen by a model of 6-deoxyerythronolide B (6-DEB) indicates it to be low
      barrier (3.8 kcal/mol) and exothermic (-2.9 kcal/mol). The combined results
      indicate the plausibility of simultaneous diprotonation of the distal oxygen of
      the reduced oxyferrous heme, leading to O-O bond scission, using the combined
      water network and 6-DEB substrate protonation agents.

PMID- 12237224
TI  - Spectroscopic studies of peroxyacetic acid reaction intermediates of cytochrome
      P450cam and chloroperoxidase.
AB  - It is generally assumed that the putative compound I (cpd I) in cytochrome P450
      should contain the same electron and spin distribution as is observed for cpd I
      of peroxidases and catalases and many synthetic cpd I analogues. In these systems
      one oxidation equivalent resides on the Fe(IV)=O unit (d(4), S=1) and one is
      located on the porphyrin (S'=1/2), constituting a magnetically coupled ferryl
      iron-oxo porphyrin pi-cation radical system. However, this laboratory has
      recently reported detection of a ferryl iron (S=1) and a tyrosyl radical
      (S'=1/2), via Mossbauer and EPR studies of 8 ms-reaction intermediates of
      substrate-free P450cam from Pseudomonas putida, prepared by a freeze-quench
      method using peroxyacetic acid as the oxidizing agent [Schunemann et al., FEBS
      Lett. 479 (2000) 149]. In the present study we show that under the same reaction
      conditions, but in the presence of the substrate camphor, only trace amounts of
      the tyrosine radical are formed and no Fe(IV) is detectable. We conclude that
      camphor restricts the access of the heme pocket by peroxyacetic acid. This
      conclusion is supported by the additional finding that binding of camphor and
      metyrapone inhibit heme bleaching at room temperature and longer reaction times,
      forming only trace amounts of 5-hydroxy-camphor, the hydroxylation product of
      camphor, during peroxyacetic acid oxidation. As a control we performed freeze
      quench experiments with chloroperoxidase from Caldariomyces fumago using
      peroxyacetic acid under the identical conditions used for the substrate-free
      P450cam oxidations. We were able to confirm earlier findings [Rutter et al.,
      Biochemistry 23 (1984) 6809], that an antiferromagnetically coupled Fe(IV)=O
      porphyrin pi-cation radical system is formed. We conclude that CPO and P450
      behave differently when reacting with peracids during an 8-ms reaction time. In
      P450cam the formation of Fe(IV) is accompanied by the formation of a tyrosine
      radical, whereas in CPO Fe(IV) formation is accompanied by the formation of a
      porphyrin radical.

PMID- 12237225
TI  - Specific and non-specific effects of potassium cations on substrate-protein
      interactions in cytochromes P450cam and P450lin.
AB  - Substrate binding to cytochrome P450cam is generally considered to be a two-step
      process. The first step corresponds to the entrance of the substrate, camphor,
      into the heme pocket. The second step corresponds to a spin transition (low spin-
      >high spin) of the iron in the protein-substrate complex. This spin transition is
      related to the mobility of the substrate inside the active site [Biochim Biophys
      Acta 1338 (1997) 77]. Potassium cations (K(+)) have a specific effect on the spin
      equilibrium. This is generally attributed to the K(+) ion-induced conformational
      change of tyrosine 96, the hydroxyl group of which is hydrogen bonded to the keto
      group of camphor and results in optimum substrate orientation and reduced
      mobility of this substrate in the active site. In the present paper, we show that
      K(+) not only affects the substrate-Tyr 96 couple, but acts more globally since
      K(+) effects are also observed in the Tyr96Phe mutant as well as in complexes
      with camphor-analogues. Large compounds, that fit well in the heme pocket and
      bind with higher affinity than camphor, display high spin contents that are less
      dependent on the presence of K(+). In contrast, K(+) has a significant effect on
      the high spin content of substrate-cytochrome P450cam complexes with looser
      interactions. We conclude that large compounds with higher affinities than
      camphor have more van der Waals contacts with the active site residues. Their
      mobilities are then reduced and less dependent on the presence of K(+). In this
      study, we also explored, for comparison, the K(+) effect on the spin transition
      state of another member of the P450 superfamily, cytochrome P450lin. This effect
      is not as strong as those observed for cytochrome P450cam. Even though the spin
      equilibrium does not change dramatically in the presence of K(+) or Na(+), the
      value of the dissociation constant (K(d)) for linalool binding is significantly
      affected by ionic strength. Analysis of the thermodynamic parameters for the
      linalool binding strongly suggests that, similarly to our previous finding for
      cytochrome P450cam, electrostatic gates participate in the control of substrate
      access.

PMID- 12237226
TI  - Intermolecular electron transfer in cytochrome P450cam covalently bound with
      Tris(2,2'-bipyridyl)ruthenium(II): structural changes detected by FTIR
      spectroscopy.
AB  - Using Fourier transform infrared spectroscopy (FTIR) we have monitored the
      changes in the protein structure following photoinduced electron transfer from
      Ru(bpy)(3)(2+) covalently attached to cysteine 334 on the surface of cytochrome
      P450cam (CYP101). The FTIR difference spectra between the oxidized and reduced
      form indicate changes in a salt link and the secondary structure (alpha-helix and
      turn regions). Photoreduction was carried out in the presence of carbon monoxide
      in order to prove the reduction of the heme iron by means of the appearance of
      the characteristic CO stretch vibration infrared band at 1940 cm(-1) for the
      camphor-bound protein. This infrared band has also been used to estimate electron
      transfer rates. The observed rates depend on the protein concentration,
      indicating that intermolecular electron transfer occurs between the labeled
      molecules.

PMID- 12237227
TI  - Why do nitric oxide synthases use tetrahydrobiopterin?
AB  - We are combining stopped-flow, stop-quench, and rapid-freezing kinetic methods to
      help clarify the unique redox roles of tetrahydrobiopterin (H(4)B) in NO
      synthesis, which occurs via the consecutive oxidation of L-arginine (Arg) and N
      hydroxy-L-arginine (NOHA). In the Arg reaction, H(4)B radical formation is
      coupled to reduction of a heme Fe(II)O(2) intermediate. The tempo of this
      electron transfer is important for coupling Fe(II)O(2) formation to Arg
      hydroxylation. Because H(4)B provides this electron faster than can the NOS
      reductase domain, H(4)B appears to be a kinetically preferred source of the
      second electron for oxygen activation during Arg hydroxylation. A conserved Trp
      (W457 in mouse inducible NOS) has been shown to influence product formation by
      controlling the kinetics of H(4)B electron transfer to the Fe(II)O(2)
      intermediate. This shows that the NOS protein tunes H(4)B redox function. In the
      NOHA reaction the role of H(4)B is more obscure. However, existing evidence
      suggests that H(4)B may perform consecutive electron donor and acceptor functions
      to reduce the Fe(II)O(2) intermediate and then ensure that NO is produced from
      NOHA.

PMID- 12237228
TI  - Assembly and activation of heme-deficient neuronal NO synthase with various
      porphyrins.
AB  - The heme prosthetic group of NO synthase is critical for catalytic activity as
      well as assembly of the enzyme to the native homodimeric form. In the current
      study, we examined if structurally different metal porphyrins could substitute
      for the native heme prosthetic group in neuronal NO synthase (nNOS) with regard
      to assembly and catalysis. We established, with the use of a recently developed
      in vitro method that functionally reconstitutes heme-deficient apo-nNOS, that Fe
      mesoporphyrin IX or Fe-deuteroporphyrin IX can substitute for heme and lead to
      assembly of a functional nNOS, albeit with lower activity. Fe-protoporphyrin IX
      dimethyl ester or the metal free protoporphyrin IX, however, lead to minimal
      assembly of nNOS. Protoporphyrin IX compounds where the native Fe was substituted
      with Zn, Mn, Co, or Sn lead to assembly of nNOS, but no detectable NO was
      synthesized in the presence of NADPH and L-arginine. Thus, the presence of the
      metal and propionic acid groups, but not the vinyl moieties, of heme are
      important structural features in assembly of nNOS. These studies establish that
      the mechanism of assembly and catalysis of nNOS can be probed with structurally
      diverse metal porphyrins.

PMID- 12237229
TI  - Mesopone cytochrome c peroxidase: functional model of heme oxygenated oxidases.
AB  - The effect of heme ring oxygenation on enzyme structure and function has been
      examined in a reconstituted cytochrome c peroxidase. Oxochlorin derivatives were
      formed by OsO(4) treatment of mesoporphyrin followed by acid-catalyzed pinacol
      rearrangement. The northern oxochlorin isomers were isolated by chromatography,
      and the regio-isomers assignments determined by 2D COSY and NOE 1H NMR. The major
      isomer, 4-mesoporphyrinone (Mp), was metallated with FeCl(2) and reconstituted
      into cytochrome c peroxidase (CcP) forming a hybrid green protein, MpCcP. The
      heme-altered enzyme has 99% wild-type peroxidase activity with cytochrome c. EPR
      spectroscopy of MpCcP intermediate compound I verifies the formation of the
      Trp(191) radical similar to wild-type CcP in the reaction cycle. Peroxidase
      activity with small molecules is varied: guaiacol turnover increases
      approximately five-fold while that with ferrocyanide is approximately 85% of
      native. The electron-withdrawing oxo-substitutents on the cofactor cause a
      approximately 60-mV increase in Fe(III)/Fe(II) reduction potential. The present
      investigation represents the first structural characterization of an oxochlorin
      protein with X-ray intensity data collected to 1.70 A. Although a mixture of R-
      and S-mesopone isomers of the FeMP cofactor was used during heme incorporation
      into the apo-protein, only the S-isomer is found in the crystallized protein.

PMID- 12237230
TI  - Deletions in the loop surrounding the iron-sulfur cluster of adrenodoxin severely
      affect the interactions with its native redox partners adrenodoxin reductase and
      cytochrome P450(scc) (CYP11A1).
AB  - The redox active iron-sulfur center of bovine adrenodoxin is coordinated by four
      cysteine residues in positions 46, 52, 55 and 92 and is covered by a loop
      containing the residues Glu-47, Gly-48, Thr-49, Leu-50 and Ala-51. In plant-type
      [2Fe-2S] ferredoxins, the corresponding loop consists of only four amino acids.
      The loop is positioned at the surface of the proteins and forms a boundary
      separating the [2Fe-2S] cluster from solvent. In order to analyze the biological
      function of the five amino acids of the loop in adrenodoxin (Adx) for this
      electron transfer protein each residue was deleted by site-directed mutagenesis.
      The resulting five recombinant Adx variants show dramatic differences among each
      other regarding their spectroscopic characteristics and functional properties.
      The redox potential is affected differently depending on the position of the
      conducted deletion. In contrast, all mutations in the protein loop influence the
      binding to the redox partners adrenodoxin reductase (AdR) and cytochrome
      P450(scc) (CYP11A1) indicating the importance of this loop for the physiological
      function of this iron--sulfur protein.

PMID- 12237231
TI  - Molecular cytogenetic analysis of clustered sporadic and familial renal cell
      carcinoma-associated 3q13 approximately q22 breakpoints.
AB  - We describe several relatives within one renal cell cancer (RCC) family sharing a
      constitutional t(2;3) (q35;q21). Based on molecular studies on several
      independent primary tumors in this family, a causative role for this
      translocation in tumor development was suggested. Subsequent positional cloning
      of the 3q21 chromosomal breakpoint revealed that this breakpoint disrupts a novel
      gene, DIRC2 (disrupted in renal cancer 2). This gene encodes an evolutionary
      conserved transmembrane protein and represents a novel member of the MFS
      superfamily of transporters. To evaluate whether DIRC2 is also targeted in
      sporadic RCC cases with cytogenetically defined 3q21 breakpoints, fluorescence in
      situ hybridization analysis was performed on metaphase spreads and/or interphase
      nuclei of 12 primary sporadic RCC using genomic clones from a 3q21 breakpoint
      spanning contig as probes. Three breakpoints were mapped proximal to the familial
      breakpoint and nine breakpoints were mapped distal to this breakpoint. Two of the
      latter breakpoints were mapped in the contig within 1 Mb distance from the
      familial breakpoint. Because these clustered 3q21 breakpoints do not coincide
      with the familial 3q21 breakpoint, they most likely affect genes distinct from
      DIRC2.

PMID- 12237232
TI  - Fluorescence in situ hybridization for the study of cell lineage involvement in
      myelodysplastic syndromes with chromosome 5 anomalies.
AB  - Fluorescence in situ hybridization (FISH) with a locus-specific dual DNA probe
      (LSI EGR-1SO/D5S23SG) for chromosome 5 was used in combination with morphology to
      study bone marrow cell lineage involvement of the abnormal chromosomal clone in
      13 patients with deletion 5q [del(5q)], either as a sole aberration or as part of
      a complex karyotype, and in six cases with monosomy 5 by metaphase cytogenetics,
      all with complex karyotypes including 2-6 marker chromosomes. In the monosomy 5
      group, only one case displayed the expected one orange and one green (1O + 1G)
      FISH pattern in a majority of the cells. The other five patients instead showed
      1O + 2G FISH signals in 17-86% of the bone marrow cells, which is the typical
      pattern for del(5q). In the del(5q) group, 26-98% of the bone marrow cells
      exhibited 1O + 2G FISH signals. All patients showed clonal involvement of the
      myeloid cell lineages, including the megakaryocytes in a few cases, whereas
      lymphoid cells generally exhibited the normal 2O + 2G FISH pattern. No difference
      was seen between patients with 5q- syndrome, those with del(5q) and a complex
      karyotype, and the monosomy 5 group. We were thus unable to confirm the recent
      suggestion that B-cells are a part of the abnormal clone in MDS with del(5q).
      Furthermore, true monosomy 5 seems to be rare in MDS.

PMID- 12237233
TI  - Banded chromosomes versus fluorescence in situ hybridization in the diagnosis of
      mantle cell lymphoma: a lesson from three cases.
AB  - We present three cases with presumptive evidence of mantle cell lymphoma (MCL)
      that were submitted for cytogenetic evaluation. Chromosome analysis showed a
      normal karyotype in two cases, while the third case showed the composite
      karyotype; 45,XY,t(1;22)(p13;q13),23,del(10)(q22),add(15)(q22),add(17)(p13). The
      characteristic t(11;14)(q13;q32) for MCL was not observed by conventional
      karyotyping in any of the cases. We furthermore evaluated the specimens by
      fluorescence in situ hybridization (FISH) using the dual-color LSI IgH/CCND1 DNA
      probe. Fusion signals, consistent with t(11;14)(q13;q32), were observed in 65%
      and 85% of interphase cells in cases 1 and 2, respectively, while the metaphases
      from both cases revealed a normal pattern. All abnormal metaphases as well as 57%
      of interphase cells from case 3 displayed a fusion signal. In the abnormal
      metaphase cells, the fused signal was located on the normally looking 14q32,
      suggesting that the IgH/CCND1 fusion resulted from the insertion of the CCND1
      gene into 14q32 adjacent to the IgH gene. Thus, FISH confirmed the diagnosis of
      MCL by showing the IgH/CCND1 fusion. In addition, these findings indicate that
      the sensitivity of FISH is superior to that of conventional cytogenetics in
      detecting t(11;14)(q13;q32) associated with MCL.

PMID- 12237234
TI  - Losses in chromosomes 17, 19, and 22q in neurofibromatosis type 1 and sporadic
      neurofibromas: a comparative genomic hybridization analysis.
AB  - Neurofibromatosis type 1 (von Recklinghausen's NF1) is an autosomal dominant
      disease associated with an increased risk of benign and malignant neoplasia
      including malignant peripheral nerve sheath tumors (MPNSTs). In this study, we
      employed comparative genomic hybridization (CGH) to determine changes in the
      relative chromosome copy number in 24 patients with neurofibromas, including 12
      NF1-associated and 12 sporadic cases. Differences in the frequency and
      distribution of chromosomal imbalances were observed in both NF1-asociated and
      sporadic neurofibromas. Chromosomal imbalances were more common in NF1-associated
      tumors than in sporadic neurofibromas. In both groups, the number of losses was
      higher than the number of gains, suggesting a predominant role of tumor
      suppressor gene in tumorigenesis. A number of new chromosomal imbalances were
      noted including chromosomes 17, 19, and chromosome arm 22q, which may be related
      to oncogenes or tumor suppressor genes in neurofibromas. In NF1-associated
      neurofibromas, the most frequent losses were found in chromosome 17 (the minimal
      common regions were 17p11.2-->p13 in nine cases and 17q24-->q25 in six cases) and
      19p (19p13.2 in nine cases). In addition, both NF1-associated and sporadic
      neurofibromas often exhibited losses at chromosome arms 19q and 22q (in NF1
      tumors, the minimal common regions were 19q13.2-->qter in seven cases).

PMID- 12237235
TI  - Comparative genomic hybridization detects specific cytogenetic abnormalities in
      pediatric ependymomas and choroid plexus papillomas.
AB  - Pathogenesis and genetic abnormalities of ependymomas are not well known and
      differential diagnosis with choroid plexus tumors may be difficult when these
      tumors are located in the ventricles. We analyzed 16 samples of primary pediatric
      ependymomas and seven choroid plexus tumors for significant gains or losses of
      genomic DNA, using comparative genomic hybridization (CGH). Four ependymoma
      samples were obtained after surgery for relapse, including one patient whose
      tumor was analyzed at diagnosis and at first and second relapses. Three out of 16
      ependymomas and none of the choroid plexus tumors appeared normal by CGH. In the
      remaining ependymomas, the number of regions with genomic imbalance was limited.
      The most frequent copy number abnormality in ependymomas was 22q loss. In one
      patient from whom multiple samples could be analyzed during tumor progression, no
      abnormality was present at diagnosis; gain of chromosome 9 and loss of 6q were
      observed at first relapse and, at second relapse, additional genomic imbalances
      were loss of 3p, 10q, and chromosome 15. In choroid plexus tumors, recurrent
      abnormalities were gains of chromosome 7 and region 12q. The recurrent
      chromosomal abnormalities were clearly different between ependymomas and choroid
      plexus papillomas (CPP). Recurrent loss of 22q suggests that this region harbors
      tumor suppressor genes important in the pathogenesis of ependymomas; however,
      other pathogenic pathways may exist involving 6q and chromosome 10 losses or gain
      of 1q and chromosome 9. CPP can be distinguished from ependymoma on the basis of
      CGH abnormalities.

PMID- 12237236
TI  - Spontaneous clinical and cytogenetic remission of aplastic anemia in a patient
      with del(13q).
AB  - We describe the case of a 64-year-old Japanese man with pancytopenia. Bone marrow
      biopsy findings were consistent with aplastic anemia. The patient was treated by
      transfusions without immunosuppressive therapy. Chromosome analysis of bone
      marrow cells at 6 months after onset showed a 46,XY,del(13) (q14q22) karyotype.
      The pancytopenia resolved gradually over the next 5 years; chromosome analysis of
      bone marrow cells at that time yielded normal findings. To our knowledge, this is
      the first report of spontaneous hematologic and cytogenetic remission of aplastic
      anemia. These findings suggest that the abnormal clone with deletion of the long
      arm of chromosome 13 was not sufficient for clonal evolution in aplastic anemia
      in this case.

PMID- 12237237
TI  - High resolution analysis of chromosome 18 alterations in ulcerative colitis
      related colorectal cancer.
AB  - We previously have demonstrated by comparative genomic hybridization that 80% of
      ulcerative colitis-related cancers show loss of all or part of chromosome 18, the
      site of at least three candidate tumor suppressor genes: DCC, SMAD2, and SMAD4.
      To determine whether these genes are targeted in colitis-related carcinogenesis,
      we performed a high-resolution analysis of chromosome 18 alteractions in 32
      colitis-related colorectal cancers by assessing allelic imbalance at 11
      microsatellite markers distributed along the chromosome, and by the quantitative
      polymerase chain reaction (PCR) method (TaqMan). TaqMan analysis was used to
      determine the relative copy number of five test genes on chromosome 18 (PACAP on
      18p and DCC, SMAD2, SMAD4, and GALNR on 18q). We found allelic imbalance, as
      assessed by loss of heterozygosity, in at least one marker on chromosome 18 in 25
      of the 29 tumors (86%) successfully tested. In 14 tumors, allelic imbalance was
      detected at all informative markers on 18q, while the other 11 tumors showed only
      partial loss. Allelic imbalance was most commonly detected at D18S363 (78% of
      informative cases). This marker is in closest proximity to SMAD4. By quantitative
      PCR analysis, a relative loss of copy number of SMAD2, SMAD4, and DCC were
      detected in 40%, 57%, and 53%, respectively, of the colitis-related cancers.
      SMAD2 was retained in four tumors having loss of SMAD4 and DCC. Loss of SMAD4
      alone was seen in one tumor. The present data indicate that the loss of SMAD4 and
      DCC occurs in the majority of colitis-related cancers.

PMID- 12237238
TI  - Transient myeloproliferative disorder in a phenotypically normal infant with
      i(21q) mosaicism.
AB  - We report a case of transient myeloproliferative disorder (TMD) that occurred in
      a phenotypically normal infant with low level constitutional mosaicism of i(21q).
      To the best of our knowledge, this is the first documented case of TMD with
      constitutional i(21q) mosaicism.

PMID- 12237239
TI  - Molecular cytogenetic characterization of a complex rearrangement involving
      chromosomes 9 and 22 in a case of Ph-negative chronic myeloid leukemia.
AB  - The "golden path", produced by the Human Genome Project effort, is composed of a
      collection of overlapping and fully sequenced BAC/PAC clones covering almost
      completely the human genome. These clones can be advantageously exploited as
      fluorescence in situ hybridization (FISH) probes for the characterization of
      rearrangements frequently found in tumors. Breakpoint characterization can be
      further refined by generating additional smaller FISH probes through LONG-PCR
      amplification of specific DNA segments, 5-10 kb in size, using appropriate
      BAC/PAC probes as template. We report here an example of this approach that has
      been used to characterize a complex Ph-negative chronic myeloid leukemia (CML Ph
      ) case in which the BCR/ABL fusion gene was found located on chromosome 9.

PMID- 12237240
TI  - Precursor T-lymphoblastic leukemia with a novel t(1;22)(p34;q13).
AB  - A 37-year-old woman that presented with cervical lymphadenopathy and leukocytosis
      was found to have precursor T-lymphoblastic leukemia (T-ALL). Cytogenetic study
      of the leukemic cells showed a 46,XX, t(1;22)(p34;q13) karyotype. The
      t(1;22)(p34;q13) is a novel chromosomal abnormality in human malignancies and is
      probably a variant form of the t(1;14)(p34;q11) found in precursor T-ALL.

PMID- 12237241
TI  - The BCR/ABL-extra signal fluorescence in situ hybridization system reliably
      detects deletions upstream of the ABL locus: implications for reporting of
      results and followup of chronic myelogenous leukemia patients.

PMID- 12237242
TI  - Mutations in the runt homology domain of CBFalpha2 in myeloid malignancies with
      acquired trisomy 21.

PMID- 12237243
TI  - Myelodysplastic syndrome with transformation to AML-M7 in a 46,XX male patient.

PMID- 12237244
TI  - Androgen receptors in prostate cancer.
AB  - The androgen receptor (AR), a transcription factor that mediates the action of
      androgens in target tissues, is expressed in nearly all prostate cancers.
      Carcinoma of the prostate is the most frequently diagnosed neoplasm in men in
      industrialized countries. Palliative treatment for non-organ-confined prostate
      cancer aims to down-regulate the concentration of circulating androgen or to
      block the transcription activation function of the AR. AR function during
      endocrine therapy was studied in tumor cells LNCaP subjected to long-term steroid
      depletion; newly generated sublines could be stimulated by lower concentrations
      of androgen than parental cells and showed up-regulation of AR expression and
      activity as well as resistance to apoptosis. Androgenic hormones regulate the
      expression of key cell cycle regulators, cyclin-dependent kinase 2 and 4, and
      that of the cell cycle inhibitor p27. Inhibition of AR expression could be
      achieved by potential chemopreventive agents flufenamic acid, resveratrol,
      quercetin, polyunsaturated fatty acids and interleukin-1beta, and by the
      application of AR antisense oligonucleotides. In the clinical situation, AR gene
      amplification and point mutations were reported in patients with metastatic
      disease. These mutations generate receptors which could be activated by other
      steroid hormones and non-steroidal antiandrogens. In the absence of androgen, the
      AR could be activated by various growth-promoting (growth factors, epidermal
      growth factor receptor-related oncogene HER-2/neu) and pleiotropic (protein
      kinase A activators, interleukin-6) compounds as well as by inducers of
      differentiation (phenylbutyrate). AR function is modulated by a number of
      coactivators and corepressors. The three coactivators, TIF-2, SRC-1 and RAC3, are
      up-regulated in relapsed prostate cancer. New experimental therapies for prostate
      cancer are aimed to down-regulate AR expression and to overcome difficulties
      which occur because of the acquisition of agonistic properties of commonly used
      antiandrogens.

PMID- 12237245
TI  - In vitro assay-assisted treatment selection for women with breast or ovarian
      cancer.
AB  - The selection of chemotherapy for women with breast or ovarian carcinoma has been
      traditionally based on results from phase III comparative trials that define the
      most active drugs and drug combinations. This approach has led to a significant
      prolongation of the lives of these patients. Unfortunately, few patients with
      advanced stage IV disease are cured using the currently available regimens. In
      order to improve the selection process for individual patients, various types of
      in vitro tests that assess the activity of standard drugs on a patient's tumor
      have been developed over the past five decades. As with bacterial culture and
      sensitivity tests, significant predictive correlations between in vitro drug
      response assays and cancer patient response and survival have been demonstrated.
      Medicare currently covers in vitro drug-resistance assays. This review discusses
      the historical development of in vitro drug-response assays and the clinical
      validation of various technologies currently available to assist the clinician in
      selecting the optimal therapy for each patient.

PMID- 12237246
TI  - The biology of neoadjuvant chemotherapy for breast cancer.
AB  - Neoadjuvant/pre-surgical medical therapy of breast cancer provides a unique
      opportunity to derive biological information related to tumour response. Large
      clinical trials of neoadjuvant chemotherapy have established that pathological
      complete remission is an independent predictor of improved disease-free survival.
      Clinical response has been found to parallel substantial reductions in the
      proliferation of breast cancer cells. Increased apoptosis also occurs, but it is
      not closely associated with response. Numerous biological markers such as p53,
      bcl-2, oestrogen receptor (ER) and HER2 have been assessed for their possible
      role in chemoresistance/response, but the data are not clear at this stage.
      Continuing work using cDNA microarrays may yield new, more reliable indices of
      likely response and an improved insight into biological processes related to
      chemotherapeutic response.

PMID- 12237247
TI  - Interactions between radiotherapy and endocrine therapy in breast cancer.
AB  - Whenever radiation therapy is given with curative intent there is the risk of
      serious damage to normal tissue. This risk increases with the dose of radiation,
      as does the probability of local tumour control. In the attempt to cure, the
      doses reach a level that inevitably causes some undesirable adverse effects,
      ranging from undetectable, or minimal, to unacceptably severe. Over the last few
      years, a number of reports have suggested that the prediction of normal tissue
      response after radiotherapy may be achieved by assays on samples withdrawn from
      the patients prior to treatment, although recent reports have described mixed
      results. The ability to predict tumour response to anti-hormones in patients with
      breast cancer has important implications with regard to treatment. Recent
      discoveries promise to provide individualized treatment options. However, there
      are no data to support that, used jointly, the combination of radiotherapy and
      hormone therapy may achieve an enhancement of breast cancer tumour response.
      Nowadays, development in cancer therapy is increasingly arising out of studies in
      basic science; its implementation in the hands of clinicians is improving the
      management of patients with cancer. In addition, as the biological aspects of
      irradiation and hormonal therapy offer an explanation, at least in part, for the
      outcome observed in patients with breast cancer after therapy, we have focused
      this review on trying to analyse the most relevant experimental research about
      the relative roles of radiotherapy and hormonal therapy, the corresponding side
      effects and, taking into account recent advances, future areas of research that
      we consider of major importance in the field.

PMID- 12237249
TI  - A new ligand for the urotensin II receptor.
AB  - The cyclic peptide human urotensin II (U-II) has been recently recognized as the
      endogenous ligand of an orphan GPCR, subsequently named the UT receptor. No
      synthetic ligands are available for investigating this novel peptide-receptor
      system. A novel UT receptor ligand, [Orn(8)]U-II, was synthesized and evaluated
      in calcium functional assays performed on HEK293 cells expressing the recombinant
      rat and human UT receptor and in the rat aorta bioassay. [Orn(8)]U-II behaves as
      a full agonist (pEC(50) approximately equal 8) at both human and rat UT receptors
      in the FlipR calcium assay eliciting similar maximal effects as the natural
      ligand U-II. On the contrary, in the rat aorta bioassay, [Orn(8)]U-II behaves as
      a competitive and selective antagonist (pA(2)=6.56) showing however a small but
      consistent residual agonist activity. It is therefore proposed that [Orn(8)]U-II
      is a partial agonist at UT receptors.

PMID- 12237248
TI  - Pharmacology and potential therapeutic applications of nitric oxide-releasing non
      steroidal anti-inflammatory and related nitric oxide-donating drugs.
AB  - This review examines the biological significance, therapeutic potential and
      mechanism(s) of action of a range of nitric oxide-releasing non-steroidal anti
      inflammatory drugs (NO-NSAID) and related nitric oxide-releasing donating drugs
      (NODD). The slow release of nitric oxide (NO) from these compounds leads to
      subtle changes in the profile of pharmacological activity of the parent, non
      steroidal anti-inflammatory drugs (NSAID). For example, compared with NSAID, NO
      NSAID cause markedly diminished gastrointestinal toxicity and improved anti
      inflammatory and anti-nociceptive efficacy. In addition, nitroparacetamol
      exhibits hepatoprotection as opposed to the hepatotoxic activity of paracetamol.
      The possibility that NO-NSAID or NODD may be of therapeutic benefit in a wide
      variety of disease states including pain and inflammation, thrombosis and
      restenosis, neurodegenerative diseases of the central nervous system, colitis,
      cancer, urinary incontinence, liver disease, impotence, bronchial asthma and
      osteoporosis is discussed.

PMID- 12237250
TI  - Augmentation of allergic inflammation in prostanoid IP receptor deficient mice.
AB  - 1 To evaluate the role of prostaglandin I(2) (PGI(2)) in allergic inflammation,
      allergic responses in the airway, skin and T cells were studied in mice lacking
      the receptor for PGI(2) (the prostanoid IP receptor) through gene disruption. 2
      Three inhalations of antigen caused an increase in plasma extravasation,
      leukocyte accumulation and cytokine (interleukin (IL)-4 and IL-5) production in
      the airway of sensitized mice. These airway inflammatory responses were
      significantly greater in IP receptor deficient mice than in wild-type mice. 3 The
      vascular leakage caused by passive cutaneous anaphylaxis, substance P and 5
      hydroxytryptamine was markedly increased in the skin of IP receptor deficient
      mice, compared with comparably treated wild-type mice. 4 The inhalation of
      antigen in sensitized mice resulted in increased serum antigen specific IgE,
      total IgE and IgG levels. The magnitude of the elevations of each immunoglobulin
      level in IP receptor deficient mice is notably higher than that in wild-type
      mice. To elucidate the mechanism of an enhancement of immunoglobulin production,
      the activity of T cells in sensitized and non-sensitized mice was studied by
      means of the production of cytokines. The antigen-induced IL-4 production by
      spleen cells from sensitized IP receptor deficient mice was almost three times
      greater than that in wild-type mice. On the contrary, the anti-CD3 antibody
      induced interferon-gamma production by CD4(+) T cells from non-sensitized IP
      receptor deficient mice was significantly lower than that in wild-type mice. 5
      The present data indicate that IP receptor deficiency reinforced an allergic
      airway and skin inflammation by augmentation of vascular permeability increase
      and the T helper 2 cell function. These findings suggest a regulatory role of
      PGI(2) in allergic inflammation.

PMID- 12237251
TI  - Ca(2+) entry blocking and contractility promoting actions of norbormide in single
      rat caudal artery myocytes.
AB  - 1 Aim of the present study was to investigate the effects of norbormide, a
      selective vasoconstrictor agent of the rat peripheral vessels, on the whole-cell
      voltage-dependent L-type Ca(2+) current (I(Ca(L))) of freshly isolated smooth
      muscle cells from the rat caudal artery, using either the conventional or the
      amphotericin B-perforated whole-cell patch-clamp method. 2 Norbormide decreased L
      type Ca(2+) current in a concentration- and voltage-dependent manner, without
      modifying the threshold and the maximum of the current-voltage relationship.
      Norbormide-induced I(Ca(L)) inhibition was reversible upon wash-out. 3 Norbormide
      both shifted the voltage dependence of the steady-state inactivation curve to
      more negative potentials by about 16 mV, without affecting the activation curve,
      and decreased the slope of inactivation. Norbormide, however, did not modify both
      the activation and the inactivation kinetics of the I(Ca(L)). 4 Norbormide
      decreased I(Ca(L)) progressively during repetitive step depolarizations, with
      inhibition depending on the stimulation frequency (use-dependent block) as well
      as on the holding potential. 5 Addition of 50 micro M norbormide caused the
      contraction of all freshly isolated cells and also of those impaled with the
      perforated method, but not of those impaled with the conventional method (i.e.
      dialysed). 6 In conclusion, these results prove norbormide to be a vascular L
      type Ca(2+) channel inhibitor, which preferentially acts on the inactivated
      and/or open state of the channel. In rat caudal artery smooth muscle, however,
      this mechanism does not result in a vasodilating effect since it is overwhelmed
      by the mechanism underlying norbormide-induced vasoconstriction.

PMID- 12237252
TI  - Metformin enhances insulin signalling in insulin-dependent and-independent
      pathways in insulin resistant muscle cells.
AB  - 1 Metformin lowers blood glucose levels in type 2 diabetic patients. To evaluate
      the insulin sensitizing action of metformin on skeletal muscle cells, we have
      used C2C12 skeletal muscle cells differentiated in chronic presence or absence of
      insulin. 2 Metformin was added during the last 24 h of differentiation of the
      C2C12 myotubes. Insulin-stimulated tyrosine phosphorylation of insulin receptor
      (IR) and insulin receptor substrate-1 (IRS-1) was determined. 3 Chronic insulin
      treatment resulted in 60 and 40% reduction in insulin-stimulated tyrosine
      phosphorylation of IR and IRS-1, respectively. Treatment with metformin was able
      to increase the tyrosine phosphorylation of IR and IRS-1 by 100 and 90%
      respectively. 4 Chronic insulin treatment drastically reduced (45%) insulin
      stimulated phosphatidyl inositol 3-kinase (PI 3-kinase) activity. Metformin
      treatment restored PI 3-kinase activity in insulin-resistant myotubes. 5 Insulin
      stimulated glucose uptake was impaired in chronically insulin-treated myotubes.
      Metformin increased basal glucose uptake to significant levels (P<0.05), but
      metformin did not increase insulin-stimulated glucose transport. 6 All the three
      mitogen-activated protein kinases (MAPK) were activated by insulin in sensitive
      myotubes. The activation of p38 MAPK was impaired in resistant myotubes, while
      ERK and JNK were unaffected. Treatment with metformin enhanced the basal
      activation levels of p38 in both sensitive and resistant myotubes, but insulin
      did not further stimulate p38 activation in metformin treated cells. 7 Treatment
      of cells with p38 inhibitor, SB203580, blocked insulin- and metformin-stimulated
      glucose uptake as well as p38 activation. 8 Since the effect of metformin on
      glucose uptake corresponded to p38 MAPK activation, this suggests the potential
      role p38 in glucose uptake. 9 These data demonstrate the direct insulin
      sensitizing action of metformin on skeletal muscle cells.

PMID- 12237253
TI  - Protective effect of relaxin in cardiac anaphylaxis: involvement of the nitric
      oxide pathway.
AB  - 1 Relaxin (RLX) is a multifunctional hormone best known for its role in pregnancy
      and parturition, that has been also shown to influence coronary perfusion and
      mast cell activation through the generation of endogenous nitric oxide (NO). In
      this study we report on the effects of RLX on the biochemical and mechanical
      changes of ex vivo perfused hearts isolated from ovalbumin-sensitized guinea-pigs
      induced by challenge with the specific antigen. The possible involvement of NO in
      the RLX action has been also investigated. 2 A 30-min perfusion with RLX (30 ng
      ml(-1)) before ovalbumin challenge fully abated the positive chronotropic and
      inotropic effects evoked by anaphylactic reaction to the antigen. RLX also
      blunted the short-term coronary constriction following to antigen challenge.
      Conversely, perfusion with chemically inactivated RLX had no effect. 3 The
      release of histamine in the perfusate and the accumulation of calcium in heart
      tissue induced by antigen challenge were significantly decreased by RLX, while
      the amounts of nitrites in the perfusate were significantly increased, as were NO
      synthase activity and expression and cGMP levels in heart tissue. 4 These
      findings indicate that RLX has a protective effect in cardiac anaphylaxis which
      involves an up-regulation of the NO biosynthetic pathway.

PMID- 12237254
TI  - Regulation of the avidity of ternary complexes containing the human 5-HT(1A)
      receptor by mutation of a receptor contact site on the interacting G protein
      alpha subunit.
AB  - 1 Fusion proteins were constructed between the human 5-HT(1A) receptor and
      pertussis toxin-resistant forms of both G(i1)alpha and G(o1)alpha mutated at
      residue(351) from cysteine to either glycine or isoleucine. Each of these was
      expressed stably in HEK293 cells. 2 Increasing concentrations of GDP inhibited
      binding of the agonist [(3)H]-8-OH-DPAT but not the antagonist [(3)H]-MPPF to
      each construct. 3 The IC(50) for GDP was greater for constructs containing
      isoleucine at residue(351) of the G proteins compared to those with glycine at
      this position. 4 The G protein antagonist suramin had similar effects to GDP on
      the binding of [(3)H]-8-OH-DPAT. 5 The proportion of 5-HT(1A) receptor binding
      sites detected by [(3)H]-MPPF that displayed high affinity for 8-OH-DPAT was
      significantly greater when the interacting G protein contained isoleucine rather
      than glycine at residue(351). 6 The 5-HT(1A) receptor displayed similar avidity
      of interaction with G(i1)alpha and G(o1)alpha. 7 These results indicate that a
      higher avidity ternary complex is formed between 8-OH-DPAT, the 5-HT(1A) receptor
      and G proteins when isoleucine rather than glycine is located at residue(351) of
      the interacting G protein.

PMID- 12237256
TI  - Interaction of different potassium channels in cardiac repolarization in dog
      ventricular preparations: role of repolarization reserve.
AB  - 1 The aim of this study was to investigate the possible role of the interaction
      of different potassium channels in dog ventricular muscle, by applying the
      conventional microelectrode and whole cell patch-clamp techniques at 37 degrees
      C. 2 Complete block of I(Kr) by 1 micro M dofetilide lengthened action potential
      duration (APD) by 45.6+/-3.6% at 0.2 Hz (n=13). Chromanol 293B applied alone at
      10 micro M (a concentration which selectively blocks I(Ks)) did not markedly
      lengthen APD (<7%), but when repolarization had already been prolonged by
      complete I(Kr) block with 1 micro M dofetilide, inhibition of I(Ks) with 10 micro
      M chromanol 293B substantially delayed repolarization by 38.5+/-8.2% at 0.2 Hz
      (n=6). 3 BaCl(2), at a concentration of 10 micro M which blocks I(Kl) without
      affecting other currents, lengthened APD by 33.0+/-3.1% (n=11), but when I(Kr)
      was blocked with 1 micro M dofetilide, 10 micro M BaCl(2) produced a more
      excessive rate dependent lengthening in APD, frequently (in three out of seven
      preparations) initiating early afterdepolarizations. 4 These findings indicate
      that if only one type of potassium channels is inhibited in dog ventricular
      muscle, excessive APD lengthening is not likely to occur. Dog ventricular
      myocytes seem to repolarize with a strong safety margin ('repolarization
      reserve'). However, when this normal 'repolarization reserve' is attenuated,
      otherwise minimal or moderate potassium current inhibition can result in
      excessive and potentially proarrhythmic prolongation of the ventricular APD.
      Therefore, application of drugs which are able to block more than one type of
      potassium channel is probably more hazardous than the use of a specific inhibitor
      of one given sort of potassium channel, and when simultaneous blockade of several
      kinds of potassium channel may be presumed, a detailed study is needed to define
      the determinants of 'repolarization reserve'.

PMID- 12237255
TI  - Pharmacological analysis for mechanisms of GPI-80 release from tumour necrosis
      factor-alpha-stimulated human neutrophils.
AB  - 1 GPI-80, a glycosylphosphatidylinositol (GPI)-anchored protein initially
      identified on human neutrophils, plays a role(s) in the regulation of beta2
      integrin function. Previous studies have shown that GPI-80 is sublocated in
      secretory vesicles. It is also found in soluble form in the synovial fluid of
      rheumatoid arthritis patients, and in the culture supernatant of formyl-methionyl
      leucyl-phenylalanine-stimulated neutrophils. To understand the behaviour of GPI
      80 under conditions of stimulation, we investigated the effects of tumour
      necrosis factor (TNF)-alpha on its expression and release. We also probed the
      mechanism of its release with various pharmacologic tools. 2 TNF-alpha induced
      the release of GPI-80 from human neutrophils in a concentration- and time
      dependent manner (in the range of 1-100 u ml(-1) and 30-120 min, respectively),
      but did not affect surface GPI-80 levels. 3 Cytochalasin B, genistein, and
      SB203580 but not PD98059 inhibited TNF-alpha-stimulated GPI-80 release and
      neutrophil adherence at the same concentration. In addition, TNF-alpha-induced
      GPI-80 release was inhibited by blocking monoclonal antibodies specific to
      components of Mac-1 (CD11b and CD18). 4 Antioxidants (pyrrolidine dithiocarbamate
      and N-acetyl-L-cysteine) inhibited GPI-80 release by TNF-alpha stimulation, but
      superoxide dismutase did not. Antioxidants but not superoxide dismutase reduced
      an intracellular oxidation state. 5 These findings indicate that TNF-alpha
      stimulated GPI-80 release from human neutrophils depends upon adherence via beta2
      integrins. They also suggest that cytochalasin B, genistein, and SB203580 inhibit
      GPI-80 release by suppressing signals for cell adherence, rather than by a direct
      effect on its secretion. Finally, we suggest that GPI-80 release involves an
      intracellular change in a redox state.

PMID- 12237257
TI  - Pharmacological characterization of the novel nociceptin/orphanin FQ receptor
      ligand, ZP120: in vitro and in vivo studies in mice.
AB  - 1 This study reports on the pharmacological characterization of ZP120, a novel
      ligand of the nociceptin/orphanin FQ (N/OFQ) peptide receptor, NOP. ZP120 is a
      structure inducing probes modified NOP ligand: Zealand Pharma proprietary SIP
      technology was used to increase the enzymatic stability and half-life of peptide.
      2 In vitro, ZP120 mimicked the inhibitory effects of N/OFQ in the electrically
      stimulated mouse vas deferens, showing however higher potency (pEC(50) 8.88 vs
      7.74), lower maximal effects (E(max) 69+/-5% vs 91+/-2%), and slower onset of
      action. Like N/OFQ, the effects of ZP120 were not modified by 1 micro M naloxone,
      but they were antagonized by the NOP receptor selective antagonist J-113397
      (pA(2) 7.80 vs ZP120, 7.81 vs N/OFQ). 3 In vivo, ZP120 mimicked the effects of
      N/OFQ, producing pronociceptive effects in the tail withdrawal assay and
      decreased locomotor activity after i.c.v., but not after i.v. administration in
      mice. ZP120 elicited similar maximal effects as N/OFQ, but it was about 10 fold
      more potent and its effects lasted longer. 4 In conclusion, the novel NOP
      receptor ligand ZP120 is a highly potent and selective partial agonist of the NOP
      receptor with prolonged effects in vivo.

PMID- 12237258
TI  - Inhibition of neuronal nicotinic acetylcholine receptors by the abused solvent,
      toluene.
AB  - 1 Toluene is a representative example of a class of industrial solvents that are
      voluntarily inhaled as drugs of abuse. Previous data from this lab and others has
      shown that toluene modulates the function of N-methyl-D-aspartate (NMDA), gamma
      aminobutyric acid (GABA) and glycine receptors at concentrations that do not
      affect non-NMDA receptors. 2 We utilized two-electrode voltage-clamp and whole
      cell patch-clamp techniques to assess the effects of toluene on neuronal
      nicotinic acetylcholine receptors expressed in oocytes and cultured hippocampal
      neurons. Toluene (50 micro M to 10 mM) produced a reversible, concentration
      dependent inhibition of acetylcholine-induced current in Xenopus oocytes
      expressing various nicotinic receptor subtypes. The alpha4beta2 and alpha3beta2
      subunit combinations were significantly more sensitive to toluene inhibition than
      the alpha4beta4, alpha3beta4 and alpha7 receptors. 3 Receptors composed of alpha4
      and beta2(V253F) subunits showed alpha4beta4-like toluene sensitivity while those
      containing alpha4 and beta4(F255V) subunits showed alpha4beta2-like sensitivity.
      4 In hippocampal neurons, toluene (50 micro M to 10 mM) dose-dependently
      inhibited ACh-mediated responses with an IC(50) of 1.1 mM. 5 Taken together,
      these results suggest that nicotinic receptors, like NMDA receptors, show a
      subunit-dependent sensitivity to toluene and may represent an important site of
      action for some of the neurobehavioural effects of toluene.

PMID- 12237259
TI  - Oral single high-dose aspirin results in a long-lived inhibition of anodal
      current-induced vasodilatation.
AB  - 1 Acetyl salicyclic acid (aspirin) irreversibly blocks cyclo-oxygenase (COX).
      This effect is short-lived in endothelial or smooth muscle cells due to
      resynthesis but long-lived in platelets devoid of synthesis ability. Aspirin
      blocks the anodal current-induced vasodilatation, suggesting participation by
      prostaglandin (PG). We analysed the time course of the effect of aspirin as an
      indirect indicator of the origin of the PG possibly involved in anodal current
      induced vasodilatation. 2 In healthy volunteers, vasodilatation, estimated from
      the peak cutaneous vascular conductance (CVC(peak)), was recorded in the forearm
      during and in the 20 min following 5 min, 0.10 mA transcutaneous anodal current
      application, using deionized water as a vehicle. CVC(peak) was normalized to 44
      degrees C heat-induced maximal vasodilatation and expressed in per cent values.
      Experiments were performed before and at 2 and 10 h, 3, 7, 10 and 14 days after
      blinded 1-g aspirin or placebo treatment. 3 CVC(peak) (mean+/-s.d.mean) after
      aspirin vs placebo was 13.6+/-14.5 vs 65.0+/-32.1 (P<0.05) 14.7+/-4.2 vs 87.5+/
      31.9 (P<0.05), 18.1+/-10.2 vs 71.6+/-26.8 (P<0.05), 42.5+/-23.4 vs 73.3+/-26.8
      (non significant, NS), 60.2+/-24.3 vs 75.2+/-26.9 (NS), 52.1+/-18.5 vs 67.9+/
      32.1 (NS) at 2 and 10 h and at days 3, 7, 10 and 14 respectively. 4 Aspirin
      inhibition of anodal current-induced vasodilatation persists long after
      endothelial and smooth muscle cyclo-oxygenases are assumed to be restored. This
      suggests that the PG involved in this response are not endothelial- or smooth
      muscle-derived. The underlying mechanism of this unexpected long-lived inhibition
      of vasodilatation by single high dose aspirin remains to be studied.

PMID- 12237260
TI  - Transport and uptake of nateglinide in Caco-2 cells and its inhibitory effect on
      human monocarboxylate transporter MCT1.
AB  - 1 Nateglinide, a novel oral hypoglycemic agent, rapidly reaches the maximum serum
      concentration after oral administration, suggesting that it is rapidly absorbed
      in the gastrointestinal tract. The aim of this work is to clarify the intestinal
      absorption mechanism of nateglinide by means of in vitro studies. 2 We examined
      the transcellular transport and the apical uptake of [(14)C]nateglinide in a
      human colon carcinoma cell line (Caco-2). We also examined whether nateglinide is
      transported via monocarboxylate transport-1 (MCT1) by means of an uptake study
      using MCT1-expressing Xenopus laevis oocytes. 3 In Caco-2 cells, the
      transcellular transport of [(14)C]nateglinide from the apical to basolateral side
      was greater than that in the opposite direction. The uptake of [(14)C]nateglinide
      from the apical side was concentration-dependent, H(+)-dependent, and Na(+)
      independent. Kinetic analysis revealed that the Kt and Jmax values of the initial
      uptake rate of [(14)C]nateglinide were 448 micro M and 43.2 nmol mg protein(-1) 5
      min(-1), respectively. Various monocarboxylates, including salicylic acid and
      valproic acid, and glibenclamide significantly inhibited the uptake of
      [(14)C]nateglinide. 4 The uptake study using MCT1-expressing oocytes showed that
      nateglinide inhibits the MCT1-mediated uptake of [(14)C]L-lactic acid, though
      nateglinide itself is not transported by MCT1. 5 Taken together, these results
      suggest that the uptake of nateglinide from the apical membranes of Caco-2 cells
      is, at least in part, mediated by a proton-dependent transport system(s) distinct
      from MCT1.

PMID- 12237262
TI  - Decreasing amputation rates in patients with diabetes mellitus. An outcome study.
AB  - The lower-extremity amputation rate in people with diabetes mellitus is high, and
      the wound failure rate at the time of amputation is as high as 28%. Even with
      successful healing of the primary amputation site, amputation of part of the
      contralateral limb occurs in 50% of patients within 2 to 5 years. The purpose of
      this study was to provide valid outcome data before (control period) and 18
      months after (test period) implementation of a multidisciplinary team approach
      using verified methods to improve the institutional care of wounds. Retrospective
      medical chart review was performed for 118 control patients and 116 test
      patients. The amputation rate was significantly decreased during the test period,
      and the amputations that were required were at a significantly more distal level.
      No above-the-knee amputations were required in 45 patients during the test
      period, compared with 14 of 76 patients during the control period. These outcome
      data suggest that unified care is an effective approach for the patient with
      diabetic foot problems.

PMID- 12237263
TI  - A new technique for Charcot's foot reconstruction.
AB  - External fixation was used to reduce or arrest progressive degeneration in 28
      patients with Charcot's foot dislocations. Adjunctive procedures included tendo
      Achilles lengthening and application of an external bone stimulator. Advantages
      of using external fixation are that surgeries are usually performed
      percutaneously and that most patients are weightbearing in 10 to 14 days. There
      was no incidence of pin tract infection or further foot collapse, with the
      longest follow-up period being 24 months. The authors propose that use of
      external fixation with bone stimulation may be an effective alternative method of
      treating the Charcot foot.

PMID- 12237261
TI  - Pharmacological characterization of CGP 12177 at the human beta(2)-adrenoceptor.
AB  - 1 It has recently been reported that CGP 12177 can act as an agonist at a novel
      secondary site within the human beta(1)-adrenoceptor. The aim of this study was
      to undertake a detailed pharmacological study of the effects of CGP 12177 on the
      human beta(2)-adrenoceptor. 2 CGP 12177 acted as a potent partial agonist of (3)H
      cyclic AMP accumulation (log EC(50)-8.90+/-0.06) and CRE-mediated reporter gene
      transcription (log EC(50)-9.66+/-0.04) in CHO-K1 cells expressing the human
      beta(2)-adrenoceptor. These CGP-induced responses were antagonized by the beta(2)
      selective antagonist ICI 118551 (apparent log K(D) values of -8.84+/-0.15 and 
      9.51+/-0.02 for the cyclic AMP and reporter gene responses respectively). 3 CGP
      12177 was also able to antagonize both cyclic AMP and reporter gene responses to
      more efficacious beta(2)-agonists with similar log K(D) values (e.g. -9.57+/-0.15
      and -10.04+/-0.096 respectively with salbutamol as agonist). 4 (3)H-CGP 12177
      binding to beta(2)-adrenoceptors in intact CHO-beta(2) cells yielded a log K(D)
      value of -9.84+/-0.06, but indicated that the ligand dissociates very slowly from
      the receptor (t(1/2) for dissociation=65 min). However, studies with a Green
      Fluorescent Protein (GFP)-tagged beta(2)-adrenoceptor indicated that CGP 12177
      does not stimulate beta(2)-adrenoceptor internalization. 5 This study
      demonstrates that CGP 12177 is a high affinity partial agonist of both cAMP
      accumulation and CRE-mediated gene transcription at the human beta(2)
      adrenoceptor. It provides no evidence that CGP 12177 can discriminate a secondary
      site on the beta(2)-adrenoceptor analogous to that observed for the human beta(1)
      adrenoceptor. However, despite its very weak actions on cAMP accumulation, the
      potent agonist effects of CGP 12177 on CRE-mediated gene transcription at the
      human beta(2)-adrenoceptor, coupled with its long duration of action, offers a
      potential lead for drug development for the treatment of chronic inflammatory
      airway diseases.

PMID- 12237264
TI  - The biology, medical management, and podiatric implications of menopause.
AB  - Approximately 36 million women in the United States are in the postmenopausal
      phase of life, creating unique challenges for the provision of compassionate,
      comprehensive podiatric medical treatment. Long-term estrogen deprivation arising
      from menopause in association with age-related factors disproportionately
      increases the risk of ischemic heart disease, osteoporosis, and concomitant
      podiatric complications. This article discusses the physiologic basis of
      menopause, hormone replacement therapy and its effects on osteoporosis, and other
      podiatric implications of menopause. Podiatric physicians caring for larger
      numbers of peri- and postmenopausal women must formulate a comprehensive
      management plan for treating fractures that arise from a combination of estrogen
      deprivation osteoporosis and abnormal foot biomechanics.

PMID- 12237265
TI  - Ultrasonographic evaluation of plantar fascia bands. A retrospective study of 211
      symptomatic feet.
AB  - The authors measured the thickness of the medial, central, and lateral bands of
      the plantar fascia using ultrasonographic techniques in 109 symptomatic patients
      with 211 painful heels. Plantar fasciitis was diagnosed by the presence of
      plantar heel pain and tenderness of the plantar fascia on palpation and was
      correlated with plantar fascia thickness. All of the symptomatic feet had medial
      band tenderness, with an average thickness of 5.9 mm, 68% had central band
      tenderness, with an average thickness of 5.3 mm, and 26% had lateral band
      tenderness, with an average thickness of 4.4 mm. The average thickness of all
      symptomatic bands was 5.35 mm, which was significantly greater than that for all
      asymptomatic bands, which was 2.70 mm. There were also significant differences in
      the thickness of the three plantar fascia bands in symptomatic patients. A
      plantar fascia index was established consisting of the ratio of the mean
      thickness of symptomatic medial, central, and lateral plantar fascia bands to
      that of asymptomatic bands; for this study, the index value is 1.98 (5.35/2.70
      mm).

PMID- 12237266
TI  - A prospective epidemiologic survey on the prevalence of foot disease in Hong
      Kong.
AB  - A prospective epidemiologic survey on the prevalence of foot disease in Hong Kong
      found foot disease in 64% of patients screened. All of the patients were
      ethnically Chinese. Of the conditions specified in the questionnaire, fungal foot
      infection, tinea pedis, and toenail onychomycosis were the most frequently
      encountered conditions, followed by metatarsal corns, eczema, psoriasis, and pes
      planus. Vascular disease, osteoarticular pathology, diabetes mellitus, obesity,
      atopy, and participation in sports were the main factors coexisting with the foot
      conditions. Of the study population, 17% and 21% reported that their quality of
      life was affected by pain and discomfort, respectively. These percentages are
      much lower than those obtained in other studies; it may therefore be inferred
      that foot complaints are being neglected by the ethnic Chinese population in Hong
      Kong.

PMID- 12237267
TI  - Diabetic limb salvage. A team approach at a teaching institution.
AB  - In this retrospective review, 19 diabetic patients with significant lower
      extremity pathology were assessed to determine the success of limb salvage in
      cases of varying complexity. The patients were either scheduled or at risk for
      below-the-knee amputation before intervention. After the limb-salvage procedure,
      patients were followed for 4 months to 9 years. Eighteen patients went on to have
      successful procedures, avoiding below-the-knee amputation; one patient had an
      above-the-knee amputation. The results demonstrate the benefits of an aggressive
      team approach with limb salvage as a goal.

PMID- 12237268
TI  - Recognition of the flexor digitorum accessorius longus.
AB  - The flexor digitorum accessorius longus muscle was observed during a cadaveric
      surgery course on the foot and ankle for third-year podiatric medical students.
      The cadaveric foot had been amputated just proximal to the ankle level so that
      the muscle origin could not be determined; its insertion, however, was found to
      be into the flexor digitorum longus tendon, just before the tendon split into its
      digital slips. This article reviews the literature on the muscle and its clinical
      implications and describes and shows the muscle as it was seen in this case.

PMID- 12237269
TI  - Extensor hallucis longus tendon rupture repair using a fascia lata allograft.
AB  - The authors present a case of a traumatic extensor hallucis longus tendon rupture
      sustained 2 days after hallux valgus and hammer toe correction. The ruptured
      tendon, separated by a 6-cm defect, was repaired using a fascia lata allograft.
      This case demonstrates a serious complication of a commonly performed procedure
      and a salvage technique useful for dealing with large tendon defects.

PMID- 12237270
TI  - P-glycoprotein as the mediator of itraconazole-digoxin interaction.

PMID- 12237271
TI  - Secondary erythromelalgia.

PMID- 12237272
TI  - Diabetic foot care: podiatric physicians are the experts.

PMID- 12237273
TI  - Cancer risks in BRCA1 carriers: time for the next generation of studies.

PMID- 12237274
TI  - Much ado about mammography variability.

PMID- 12237275
TI  - Long Island study finds no link between pollutants and breast cancer.

PMID- 12237278
TI  - Big business: when Wall Street and cancer research collide.

PMID- 12237276
TI  - After long Island study, advocates look for a stronger voice.

PMID- 12237279
TI  - Reinvestment act may provide relief for nursing shortage.

PMID- 12237280
TI  - New imaging institute focuses its goals, plans for future.

PMID- 12237281
TI  - Cancer Incidence in BRCA1 mutation carriers.
AB  - BACKGROUND: Germline BRCA1 mutations confer a substantial lifetime risk of breast
      and ovarian cancer, but whether cancer at other sites is increased is less clear.
      To evaluate the risks of other cancers in BRCA1 mutation carriers, we conducted a
      cohort study of 11 847 individuals from 699 families segregating a BRCA1 mutation
      that were ascertained in 30 centers across Europe and North America. METHODS: The
      observed cancer incidence was compared with the expected cancer incidence based
      on population cancer rates. Relative risks (RRs) of each cancer type in BRCA1
      carriers relative to risks for the general population were estimated by weighting
      individuals according to their estimated probability of being a mutation carrier.
      All statistical tests were two-sided. RESULTS: BRCA1 mutation carriers were at a
      statistically significantly increased risk for several cancers, including
      pancreatic cancer (RR = 2.26, 95% confidence interval [CI] = 1.26 to 4.06, P
      =.004) and cancer of the uterine body and cervix (uterine body RR = 2.65, 95% CI
      = 1.69 to 4.16, P<.001; cervix RR = 3.72, 95% CI = 2.26 to 6.10, P<.001). There
      was some evidence of an elevated risk of prostate cancer in mutation carriers
      younger than 65 years old (RR = 1.82, 95% CI = 1.01 to 3.29, P =.05) but not in
      those 65 years old or older (RR = 0.84, 95% CI = 0.53 to 1.33, P =.45). Overall,
      increases in the risk for cancer at sites other than the breast or ovary were
      small and evident in women (RR = 2.30, 95% CI = 1.93 to 2.75, P =.001) but not in
      men (RR = 0.95, 95% CI = 0.81 to 1.12, P =.58). CONCLUSIONS: In carriers of BRCA1
      mutations, the overall increased risk of cancer at sites other than breast and
      ovary is small and is observed in women but generally not in men. BRCA1 mutations
      may confer increased risks of other abdominal cancers in women and increased
      risks of pancreatic cancer in men and women.

PMID- 12237282
TI  - Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation
      program.
AB  - BACKGROUND: Increasing numbers of BRCA1 mutation carriers are being identified in
      cancer risk evaluation programs. However, no estimates of cancer risk specific to
      a clinic-based population of mutation carriers are available. These data are
      clinically relevant, because estimates based on families ascertained for linkage
      studies may overestimate cancer risk in mutation carriers, and population-based
      series may underestimate it. Wide variation in risk estimates from these
      disparate ascertainment groups makes counseling in risk evaluation programs
      difficult. The purpose of this study was to estimate BRCA1-related cancer risks
      for individuals ascertained in a breast cancer risk evaluation clinic. METHODS:
      Cumulative observed and age-adjusted cancer risk estimates were determined by
      analyzing 483 BRCA1 mutation carriers in 147 families identified in two academic
      breast and ovarian cancer risk evaluation clinics. Cancer risks were computed
      from the proportion of individuals diagnosed with cancer during a 10-year age
      interval from among the total number of individuals alive and cancer-free at the
      beginning of that interval. Age-of-diagnosis comparisons were made using two
      sided Student's t tests. RESULTS: By age 70, female breast cancer risk was 72.8%
      (95% confidence interval [CI] = 67.9% to 77.7%) and ovarian cancer risk was 40.7%
      (95% CI = 35.7% to 45.6%). The risk for a second primary breast cancer by age 70
      was 40.5% (95% CI = 34.1% to 47.0%). We also identified an increased risk of
      cancer of the colon (twofold), pancreas (threefold), stomach (fourfold), and
      fallopian tube (120-fold) in BRCA1 mutation carriers as compared with
      Surveillance, Epidemiology, and End Results (SEER) Program population-based
      estimates. CONCLUSION: The estimates for breast and ovarian cancer risk in BRCA1
      mutation carriers is higher than population-based estimates but lower than
      estimates based on families ascertained for linkage studies. These cancer risk
      estimates may most closely approximate those faced by BRCA1 mutation carriers
      identified in risk evaluation clinics.

PMID- 12237283
TI  - Screening mammograms by community radiologists: variability in false-positive
      rates.
AB  - BACKGROUND: Previous studies have shown that the agreement among radiologists
      interpreting a test set of mammograms is relatively low. However, data available
      from real-world settings are sparse. We studied mammographic examination
      interpretations by radiologists practicing in a community setting and evaluated
      whether the variability in false-positive rates could be explained by patient,
      radiologist, and/or testing characteristics. METHODS: We used medical records on
      randomly selected women aged 40-69 years who had had at least one screening
      mammographic examination in a community setting between January 1, 1985, and June
      30, 1993. Twenty-four radiologists interpreted 8734 screening mammograms from
      2169 women. Hierarchical logistic regression models were used to examine the
      impact of patient, radiologist, and testing characteristics. All statistical
      tests were two-sided. RESULTS: Radiologists varied widely in mammographic
      examination interpretations, with a mass noted in 0%-7.9%, calcification in 0%
      21.3%, and fibrocystic changes in 1.6%-27.8% of mammograms read. False-positive
      rates ranged from 2.6% to 15.9%. Younger and more recently trained radiologists
      had higher false-positive rates. Adjustment for patient, radiologist, and testing
      characteristics narrowed the range of false-positive rates to 3.5%-7.9%. If a
      woman went to two randomly selected radiologists, her odds, after adjustment, of
      having a false-positive reading would be 1.5 times greater for the radiologist at
      higher risk of a false-positive reading, compared with the radiologist at lowest
      risk (95% highest posterior density interval [similar to a confidence interval] =
      1.17 to 2.08). CONCLUSION: Community radiologists varied widely in their false
      positive rates in screening mammograms; this variability range was reduced by
      half, but not eliminated, after statistical adjustment for patient, radiologist,
      and testing characteristics. These characteristics need to be considered when
      evaluating false-positive rates in community mammographic examination screening.

PMID- 12237284
TI  - The effects of malignant transformation on susceptibility of human urothelial
      cells to CD40-mediated apoptosis.
AB  - BACKGROUND: The tumor necrosis factor (TNF) superfamily of ligands and receptors
      mediates immune cell survival. Some members possess a death domain, a protein
      motif that functions to transmit apoptotic signals, whereas others, such as CD40,
      do not. CD40 is expressed by both normal and malignant epithelial cells. To
      investigate the functional significance of this expression, we studied the
      effects of ligation of CD40, Fas, and TNF receptors (TNFRs) on the proliferation
      and survival of normal and malignant human urothelial cells and urothelial cells
      with disabled p53 function. METHODS: Normal and malignant human urothelial cells
      were cultured with soluble TNF family agonists (CD40 ligand [CD40L], TNF-alpha,
      anti-Fas antibody, or cocultured with mouse fibroblasts stably transfected with
      plasmids that caused the cells to constitutively express CD40L or CD32; cell
      proliferation was estimated by an [(3)H]thymidine incorporation assay, and
      apoptosis was determined by Annexin V staining and by a DNA fragmentation assay.
      Messenger RNA levels for CD40 and potential downstream effector molecules were
      quantified by polymerase chain reaction-based and ribonuclease protection assays,
      respectively, and nuclear factor (NF) kappaB nuclear translocation was detected
      by immunofluorescence. All statistical tests were two-sided. RESULTS: Soluble
      trimeric CD40L inhibited the growth of normal and malignant urothelial cells but
      did not induce apoptosis. Cell surface-presented CD40L induced massive apoptosis
      in CD40-positive transitional cell carcinoma cells but not in normal urothelial
      cells. Normal cells underwent CD40L-mediated apoptosis only in the presence of
      other TNFR agonists. An agonistic anti-CD40 antibody presented on the surface of
      CD32-transfected fibroblasts also induced apoptosis in transitional cell
      carcinoma cells and in normal urothelial cells. Apoptotic responses of tumor (but
      not normal) cells to soluble agonists were enhanced by blocking protein
      synthesis. Karyotypically normal urothelial cells with disabled p53 function
      underwent apoptosis during coculture with CD40L-expressing fibroblasts alone but
      were not additionally sensitive to additional TNFR agonists. CONCLUSIONS:
      Susceptibility to CD40 ligation-induced apoptosis may be a novel mechanism for
      eliminating neoplastically transformed urothelial cells. Loss of CD40 expression
      may be an important adaptive mechanism for transitional cell carcinoma
      development and progression.

PMID- 12237285
TI  - Inactivation of BRCA1 and BRCA2 in ovarian cancer.
AB  - BACKGROUND: Although BRCA1 and BRCA2 play important roles in hereditary ovarian
      cancers, the extent of their role in sporadic ovarian cancers and their
      mechanisms of inactivation are not yet well understood. Our goal was to
      characterize BRCA2 mutations and mRNA expression in a group of ovarian tumors
      previously evaluated for BRCA1 mutations and mRNA expression. METHODS: The tumors
      of 92 unrelated women with "ovarian" cancer (i.e., ovarian, peritoneal, or
      fallopian tube cancer) were screened for BRCA2 null mutations using a protein
      truncation test. Methylation-specific polymerase chain reaction (PCR) was used to
      examine the BRCA2 promoter for hypermethylation in tumors that did not express
      BRCA2 mRNA. All statistical tests were two-sided. RESULTS: Nine tumors had a
      germline (n = 5) or somatic (n = 4) BRCA2 mutation; each was associated with loss
      of heterozygosity. All of the somatic (1445delC, E880X, 4286del8, and 5783delT)
      and one of the germline (5984ins4) mutations were unique to this study. One tumor
      had somatic mutations in both BRCA1 and BRCA2. Two tumors are, to our knowledge,
      the first cases of germline BRCA2-associated peritoneal cancer. Twelve additional
      tumors lacked detectable BRCA2 mRNA, but the BRCA2 promoter was hypermethylated
      in only one of them, suggesting that other mechanisms effect transcriptional
      silencing of BRCA2. Tumors lacking BRCA1 mRNA were more likely to lack BRCA2 mRNA
      than tumors expressing BRCA1 mRNA (P<.001). Overall, 82% (95% confidence interval
      [CI] = 74% to 90%) of the tumors contained alterations in BRCA1, BRCA2, or both
      genes. Of 41 informative tumors with some alteration in BRCA2, 36 also had an
      alteration in BRCA1. The frequency, but not the mechanism, of BRCA1 or BRCA2
      dysfunction in ovarian cancer was independent of family history. CONCLUSIONS:
      Multiple mechanisms cause nearly universal dysfunction of BRCA1 and/or BRCA2 in
      hereditary and sporadic ovarian carcinoma. Ovarian cancers with BRCA2 dysfunction
      often have simultaneous BRCA1 dysfunction.

PMID- 12237286
TI  - A prospective study of high-grade cervical neoplasia risk among human
      papillomavirus-infected women.
AB  - BACKGROUND: In case-control studies, smoking, parity, and oral contraceptive use
      have been associated with an increased risk of cervical intraepithelial neoplasia
      grade 3 (CIN3) and cervical cancer among women who are infected with oncogenic
      human papillomavirus (HPV). However, these potential risk factors have not been
      adequately studied in prospective studies. METHODS: We studied 1812 women who
      were enrolled in a 10-year prospective study of cervical neoplasia at Kaiser
      Permanente in Portland, Oregon, and who at enrollment had tested positive for
      oncogenic HPV DNA and had responded to a questionnaire that included questions on
      smoking, oral contraceptive use, and parity. Absolute risks and crude relative
      risks (RRs) with 95% confidence intervals (CIs) for CIN3 or cervical cancer were
      computed for three time intervals (0-8, 9-68, and 69-122 months after enrollment)
      using the Kaplan-Meier method. Conditional logistic regression models were used
      to control for factors that may have influenced our risk estimates, specifically
      the cytologic interpretation of baseline Pap smear, number of Pap smears during
      follow-up, age at enrollment, age at prediagnosis visit, and age at diagnosis.
      All statistical tests were two-sided. RESULTS: Oral contraceptive use and parity
      were not associated with risk of CIN3 or cervical cancer. Former smokers, women
      who smoked less than one pack of cigarettes per day, and women who smoked one or
      more packs per day had crude RRs for CIN3 or cervical cancer for the entire
      follow-up period of 2.1 (95% CI = 1.1 to 3.9), 2.2 (95% CI = 1.2 to 4.2), and 2.9
      (95% CI = 1.5 to 5.6), respectively, compared with never smokers. In the
      multivariable model, former smokers, women who smoked less than one pack/day, and
      women who smoked one or more packs/day had RRs of 3.3 (95% CI = 1.6 to 6.7), 2.9
      (95% CI = 1.4 to 6.1), and 4.3 (95% CI = 2.0 to 9.3), respectively, for CIN3 or
      cervical cancer compared with never smokers. CONCLUSIONS: Smoking is associated
      with an increased risk of invasive cervical cancer in women who are infected with
      oncogenic HPV. Subsequent studies should examine the role of smoking in the
      multistage pathogenesis of cervical cancer.

PMID- 12237287
TI  - Crystal structure of aurora-2, an oncogenic serine/threonine kinase.
AB  - Aurora-2 is a key member of a closely related subgroup of serine/threonine
      kinases that plays important roles in the completion of essential mitotic events.
      Aurora-2 is oncogenic and amplified in various human cancers and could be an
      important therapeutic target for inhibitory molecules that would disrupt the cell
      cycle and block proliferation. We report the first crystal structure of Aurora-2
      kinase in complex with adenosine. Analysis of residues in the active site
      suggests differences with structurally and biologically related protein kinases.
      The activation loop, which contains residues specific to the Aurora family of
      kinases, has a unique conformation. These results provide valuable insight into
      the design of selective and highly potent ATP-competitive inhibitors of the
      Aurora kinases.

PMID- 12237288
TI  - Different transcription factor binding arrays modulate the cAMP responsivity of
      the phosphoenolpyruvate carboxykinase gene promoter.
AB  - The cAMP responsiveness of the phosphoenolpyruvate carboxykinase (PEPCK) gene
      promoter is mediated by a cAMP response unit, which includes three CCAAT/enhancer
      binding protein (C/EBPs) sites, and a cAMP response element (CRE). Because both
      the CRE-binding protein and several C/EBP isoforms can to bind to the CRE with
      similar affinity, a variety of transcription factor bindings arrays in the cAMP
      response unit are possible that may affect the protein kinase A (PKA)
      responsivity of the promoter. To explore this issue, we have designed PEPCK
      promoter variants that have the native cis-elements within the cAMP response unit
      replaced with one or more LexA- and/or GAL4-binding sites. We also engineered the
      corresponding C/EBP and CRE-binding protein chimeras, which have their basic
      region leucine zipper domains replaced with LexA or GAL4 DNA-binding domains.
      Using this approach, we have reconstituted the PKA responsiveness of permissive
      PEPCK promoters in hepatoma cells and have characterized the PKA responsivity of
      the promoter under defined transcription factor occupancy patterns. Furthermore,
      analysis of deletion mutants of C/EBPalpha indicated that the domains that
      mediate its constitutive and PKA-inducible activities vary depending on which cis
      element it occupies on the PEPCK promoter. These results suggest that promoter
      context may influence which domains within a transcription factor are employed to
      mediate transactivation.

PMID- 12237289
TI  - trans-Sialidase from Trypanosoma cruzi binds host T-lymphocytes in a lectin
      manner.
AB  - Trypanosoma cruzi, the protozoan parasite responsible for Chagas' disease,
      expresses on its surface an uncommon membrane-bound sialidase, known as trans
      sialidase. trans-Sialidase is the product of a multigene family encoding both
      active and inactive proteins. We report here that an inactive mutant of trans
      sialidase physically interacts with CD4(+) T cells. Using a combination of flow
      cytometry and immunoprecipitation techniques, we identified the sialomucin CD43
      as a counterreceptor for trans-sialidase on CD4(+) T cells. Using biochemical,
      immunological, and spectroscopic approaches, we demonstrated that the inactive
      trans-sialidase is a sialic acid-binding protein displaying the same specificity
      required by active trans-sialidase. Taken together, these results suggest that
      inactive members of the trans-sialidase family can physically interact with
      sialic acid-containing molecules on host cells and could play a role in host
      cell/T. cruzi interaction.

PMID- 12237290
TI  - Targeted lysosome disruptive elements for improvement of parenchymal liver cell
      specific gene delivery.
AB  - The transfection ability of nonviral gene therapy vehicles is generally hampered
      by untimely lysosomal degradation of internalized DNA. In this study we describe
      the development of a targeted lysosome disruptive element to facilitate the
      escape of DNA from the lysosomal compartment, thus enhancing the transfection
      efficacy, in a cell-specific fashion. Two peptides (INF7 and JTS-1) were tested
      for their capacity to disrupt liposomes. In contrast to JTS-1, INF7 induced rapid
      cholesterol-independent leakage (EC(50), 1.3 microm). INF7 was therefore selected
      for coupling to a high affinity ligand for the asialoglycoprotein receptor
      (ASGPr), K(GalNAc)(2), to im- prove its uptake by parenchymal liver cells.
      Although the parent peptide disrupted both cholesterol-rich and -poor liposomes,
      the conjugate, INF7-K(GalNAc)(2), only induced leakage of cholesterol-poor
      liposomes. Given that endosomal membranes of eukaryotic cells contain <5%
      cholesterol, this implies that the conjugate will display a higher selectivity
      toward endosomal membranes. Although both INF7 and INF7-K(GalNAc)(2) were found
      to increase the transfection efficiency on polyplex-mediated gene transfer to
      parenchymal liver cells by 30-fold, only INF7-K(GalNAc)(2) appeared to do so in
      an ASGPr-specific manner. In mice, INF7-K(GalNAc)(2) was specifically targeted to
      the liver, whereas INF7 was distributed evenly over various organs. In summary,
      we have prepared a nontoxic cell-specific lysosome disruptive element that
      improves gene delivery to parenchymal liver cells via the ASGPr. Its high cell
      specificity and preference to lyse intracellular membranes make this conjugate a
      promising lead in hepatocyte-specific drug/gene delivery protocols.

PMID- 12237291
TI  - Calcitonin down-regulates E-cadherin expression in rodent uterine epithelium
      during implantation.
AB  - Previous studies indicated that calcitonin (CT), a peptide hormone involved in
      calcium homeostasis, is transiently expressed in the receptive rat and human
      endometrial epithelia within the window of implantation. Attenuation of uterine
      CT expression using antisense methods severely impaired implantation in the rat.
      The molecular pathway of CT in the pregnant uterus, however, remains unknown. In
      the present study, we investigated the cellular events following the binding of
      CT to its membrane receptors in human endometrial epithelial cell line Ishikawa.
      We observed that CT treatment triggers a transient rise in intracellular calcium
      in these cells. Most interestingly, CT treatment also led to the disappearance of
      E-cadherin, a critical cell adhesion molecule, from cell-cell contact sites.
      Blockade of intracellular calcium release by BAPTA-AM (1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl) prevented the CT
      induced disappearance of E-cadherin. Our studies further revealed that CT
      treatment markedly down-regulates the level of E-cadherin mRNA in Ishikawa cells.
      We also examined whether CT influences the expression of E-cadherin mRNA in
      intact rat uterine tissue during implantation. In pregnant rats, high levels of E
      cadherin mRNA were expressed during the first 3 days of gestation when the CT
      mRNA in uterine epithelial cells is undetectable. Concomitant with a transient
      burst of CT expression during days 4-5 of pregnancy, the level of E-cadherin mRNA
      declined sharply. Furthermore, administration of exogenous CT to animals on day 2
      of pregnancy led to a premature suppression of E-cadherin mRNA level on day 3,
      indicating a direct link between elevated levels of uterine CT and the down
      regulation of E-cadherin expression in the surface epithelium. Collectively, our
      results are consistent with the hypothesis that CT-induced reduction in E
      cadherin expression may remodel the adherens junctions between epithelial cells,
      and this change in epithelial cell phenotype might be a critical event during the
      implantation of the blastocyst.

PMID- 12237292
TI  - Carboxyl terminus of hVIP/mov34 is critical for HIV-1-Vpr interaction and
      glucocorticoid-mediated signaling.
AB  - Human immunodeficiency virus, type 1 (HIV-1) vpr is a highly conserved gene among
      lentiviruses. The diverse functions of Vpr support interactions of this HIV
      accessory protein with host cell partners of important pathways. hVIP/mov34
      (human Vpr Interacting Protein) is one of these identified Vpr ligands. hVIP is a
      34-kDa member of the eIF3 family that is vital for early embryonic development in
      transgenic mice and important in cell cycle regulation. Its interaction with Vpr,
      however, is not yet clearly defined. Therefore, we constructed a panel of
      deletion mutants of this cytoplasmic cellular ligand to map the protein domain
      that mediates its interaction with Vpr. We observed that the carboxyl-terminal
      region of hVIP is critical for its interaction with Vpr. In the absence of Vpr or
      HIV infection, full-length hVIP is expressed in the cytoplasm. The cytoplasmic
      localization pattern of full-length hVIP protein, however, is shifted to a clear
      nuclear localization pattern in cells expressing both hVIP and Vpr. In contrast,
      Vpr did not alter the localization pattern of hVIP mutants, which have their
      carboxyl-terminal domain deleted. The movement of hVIP supported prior work that
      suggested that Vpr triggers activation of the GR receptor complex. In fact, we
      also observed that dexamethasone moves hVIP into the nucleus and that
      glucocorticoid antagonists inhibit this effect. Interestingly, the expression of
      an hVIP carboxyl-terminal mutant, which is not responsive to Vpr, is also not
      responsive to dexamethasone. These data illustrate that the carboxyl-terminal
      domain of hVIP is critical for mediating hVIP-Vpr interaction as well as for its
      glucocorticoid response. These results support the view that hVIP is a member of
      the complex array of nucleocytoplasmic shuttling proteins that are regulated by
      HIV infection and glucocorticoids.

PMID- 12237293
TI  - Elucidation of molecular events mediating induction of apoptosis by synthetic
      retinoids using a CD437-resistant ovarian carcinoma cell line.
AB  - Retinoids have great promise in the area of cancer therapy and chemoprevention.
      Although some tumor cells are sensitive to the growth inhibitory effect of all
      trans-retinoic acid (ATRA), many ovarian tumor cells are not. 6-((1-Admantyl)-4
      hydroxyphenyl)-2-naphthalenecarboxylic acid (CD437) is a conformationally
      restricted synthetic retinoid that induces growth arrest and apoptosis in both
      ATRA-sensitive and ATRA-resistant ovarian tumor cell lines. To better understand
      the mechanism by which CD437 induces apoptosis in ovarian tumor cell lines, we
      prepared a cell line, CA-CD437R, from the ATRA-sensitive ovarian cell line, CA-OV
      3, which was resistant to CD437. We found that the CD437-resistant cell line was
      also resistant to the induction of apoptosis by tumor necrosis factor-alpha but
      not resistant to the induction of apoptosis by another synthetic retinoid,
      fenretinide N-(4-hydroxyphenyl)retinamide. We also show that this cell line
      remains ATRA-sensitive and exhibits no deficiencies in RAR function. Analysis of
      this CD437-resistant cell line suggests that the pathway for induction of
      apoptosis by CD437 is similar to the pathway utilized by tumor necrosis factor
      alpha and different from the pathway induced by the synthetic retinoid,
      fenretinide N-(4-hydroxyphenyl)retinamide. The CA-CD437R cell line is a valuable
      tool, permitting us to further elucidate the molecular events that mediate
      apoptosis induced by CD437 and other synthetic retinoids. Results of experiments
      utilizing this cell line suggest that the alteration responsible for resistance
      of CA-CD437R cells to CD437 induced event maps after the activation of p38 and
      TR3 expression, prior to mitochondrial depolarization, subsequent release of
      cytochrome c and activation of caspase-9 and caspase-3.

PMID- 12237294
TI  - Effect of gangliosides on the distribution of a glycosylphosphatidylinositol
      anchored protein in plasma membrane from Chinese hamster ovary-K1 cells.
AB  - Glycosylphosphatidylinositol (GPI)-anchored proteins are clustered mainly in
      sphingolipid-cholesterol microdomains of the plasma membrane. The distribution of
      GPI-anchored fusion yellow fluorescent protein (GPI-YFP) in the plasma membrane
      of Chinese hamster ovary (CHO)-K1 cells with different glycolipid compositions
      was investigated. Cells depleted of glycosphingolipids by inhibiting
      glucosylceramide synthase activity or cell lines expressing different
      gangliosides caused by stable transfection of appropriate ganglioside
      glycosyltransferases or exposed to exogenous GM1 were transfected with GPI-YFP
      cDNA. The distribution of GPI-YFP fusion protein expressed at the plasma membrane
      was studied using the membrane-impermeable cross-linking agent
      bis(sulfosuccinimidyl)suberate. Results indicate that GPI-YFP forms clusters at
      the surface of cells expressing GM3, or cells depleted of glycolipids, or
      transfected cells expressing mainly GD3 and GT3, or GM1 and GD1a, or mostly GM2,
      or highly expressing GM1. However, no significant changes in membrane
      microdomains of GPI-YFP were detected in the different glycolipid environments
      provided by the membranes of the cell lines under study. On the other hand, wild
      type CHO-K1 cells exposed to 100 microm GM1 before cross-linking with
      bis(sulfosuccinimidyl)suberate showed a dramatic reduction in the amount of GPI
      YFP clusters. These findings clearly indicate that manipulating the glycolipid
      content of the cellular membrane, just by changing the ganglioside biosynthetic
      activity of the cell, did not significantly affect the association of GPI-YFP on
      the cell surface of CHO-K1 cells. The effect of exogenous GM1 gangliosides on GPI
      YFP plasma membrane distribution might be a consequence of the ganglioside level
      reached in plasma membrane and/or the effect of particular ganglioside species
      (micelles) that lead to membrane architecture and/or dynamic modifications.

PMID- 12237295
TI  - Estradiol represses human T-cell leukemia virus type 1 Tax activation of tumor
      necrosis factor-alpha gene transcription.
AB  - Adult T-cell leukemia is caused by human T-cell leukemia virus type I (HTLV-I).
      The HTLV-I Tax protein is essential for clinical manifestations because it
      activates viral and cellular gene transcription. Tax enhances production of tumor
      necrosis factor-alpha (TNF-alpha), which may lead to bone and joint destruction.
      Because estrogens might prevent osteoporosis by repressing TNF-alpha gene
      transcription, we investigated whether estrogens inhibit the transcriptional
      effects of Tax on the TNF-alpha promoter. Tax activated the -1044, -163, and -125
      TNF-alpha promoters by 9-25-fold but not the -82 promoter, demonstrating that Tax
      activation requires the -125 to -82 region, known as the TNF response element
      (TNF-RE). Three copies of the TNF-RE upstream of the minimal thymidine kinase
      promoter conferred a similar magnitude of activation by Tax. We demonstrated that
      c-Jun, NFkappaB, p50, and p65 interact with and activate the TNF-RE by using
      mutational analysis of the TNF-RE, Tax mutants that selectively activate NFkappaB
      or the cAMP-response element binding protein/activating transcription factor
      pathway, and gel shift assays with nuclear extracts. Estradiol markedly repressed
      Tax-activated transcription of the TNF-alpha gene with estrogen receptor (ER)
      alpha or beta. Nuclear extracts from U2OS cells stably transfected with ER(alpha)
      demonstrated that ERs interact with the TNF-RE. Our studies provide evidence that
      ERs repress Tax-activated TNF-alpha transcription by interacting with a c-Jun and
      NFkappaB platform on the TNF-RE. Estrogens may ameliorate bone and inflammatory
      joint diseases in patients infected with HTLV-I by repressing transcription of
      the TNF-alpha gene.

PMID- 12237296
TI  - Enhancement of alpha -helicity in the HIV-1 inhibitory peptide DP178 leads to an
      increased affinity for human monoclonal antibody 2F5 but does not elicit
      neutralizing responses in vitro. Implications for vaccine design.
AB  - The synthetic peptide DP178, derived from the carboxyl-terminal heptad repeat
      region of human immunodeficiency virus type 1 GP41 protein is a potent inhibitor
      of viral-mediated fusion and contains the sequence ELDKWA, which constitutes the
      recognition epitope for the broadly neutralizing human monoclonal antibody 2F5.
      Efforts at eliciting a 2F5-like immune response by immunization with peptides or
      fusion proteins containing this sequence have not met with success, possibly
      because of incorrect structural presentation of the epitope. Although the
      structure of the carboxyl-terminal heptad repeat on the virion is not known,
      several recent reports have suggested a propensity for alpha-helical
      conformation. We have examined DP178 in the context of a model for optimized
      alpha-helices and show that the native sequence conforms poorly to the model.
      Solution conformation of DP178 was studied by circular dichroism and NMR
      spectroscopy and found to be predominantly random, consistent with previous
      reports. NMR mapping was used to show that the low percentage of alpha-helix
      present was localized to residues Glu(662) through Asn(671), a region
      encompassing the 2F5 epitope. Using NH(2)-terminal extensions derived from either
      GP41 or the yeast GCN4 leucine zipper dimerization domain, we designed peptide
      analogs in which the average helicity is significantly increased compared with
      DP178 and show that these peptides exhibit both a modest increase in affinity for
      2F5 using a novel competitive solution-based binding assay and an increased
      ability to inhibit viral entry in a single-cycle infectivity model. Selected
      peptides were conjugated to carrier protein and used for guinea pig
      immunizations. High peptide-specific titers were achieved using these immunogens,
      but the resulting sera were incapable of viral neutralization. We discuss these
      findings in terms of structural and immunological considerations as to the
      utility of a 2F5-like response.

PMID- 12237297
TI  - Cyclooxygenase-2 expression in cultured cortical thick ascending limb of Henle
      increases in response to decreased extracellular ionic content by both
      transcriptional and post-transcriptional mechanisms. Role of p38-mediated
      pathways.
AB  - We showed previously that decreased extracellular salt or chloride up-regulates
      the cortical thick ascending limb of Henle (cTALH) COX-2 expression via a p38
      dependent pathway. The present studies determined that low salt medium increased
      COX-2 mRNA expression 3.9-fold control by 6 h in cultured cTALH, which was
      blocked by actinomycin D pretreatment, suggesting transcriptional regulation.
      Luciferase activity (normalized to beta-galactosidase activity) of the full
      length (-3400) COX-2 promoter in cTALH increased from 1.8 +/- 0.3 in control
      media to 5.8 +/- 0.7 in low salt (n = 9; p < 0.01). Low chloride medium had
      similar effects as low salt has on COX-2 promoter activity. Deletion constructs 
      815, -512, and -410 were similarly stimulated, but -385 could not be stimulated
      significantly by low salt (1.8 +/- 0.3 versus 2.4 +/- 0.5, n = 10). This
      suggested involvement of an NF-kappaB cis-element located in this region, which
      was confirmed by utilizing a construct with a point mutation of this NF-kappaB
      binding site that was not stimulated by low salt medium. Co-incubation of the
      specific p38 inhibitor, SB203580 or PD169316, inhibited a low salt-induced
      increase in luciferase activity of the intact COX-2 promoter (5.8 +/- 0.7 versus
      1.1 +/- 0.2, n = 8 and 1.4 +/- 0.4, n = 4 respectively, p < 0.01). Mobility shift
      assays indicated that the low salt medium stimulated NF-kappaB binding activity,
      and this stimulation was inhibited by p38 inhibitors. To test whether p38 also
      increased COX-2 expression by increasing mRNA stability, cTALH were incubated in
      low salt for 2 h, and actinomycin was then added with or without SB203580. p38
      inhibition led to a decreased half-life of COX-2 mRNA (from 68 to 18 min, n = 4
      7, p < 0.05). Therefore, these studies indicate that p38 stimulates COX-2
      expression in cTALH and macula densa by transcriptional regulation predominantly
      via a NF-kappaB-dependent pathway and by post-transcriptional increases in mRNA
      stability.

PMID- 12237298
TI  - Sarcolipin overexpression in rat slow twitch muscle inhibits sarcoplasmic
      reticulum Ca2+ uptake and impairs contractile function.
AB  - Sarcolipin (SLN) is an inhibitor of sarco(endo)plasmic reticulum Ca(2+)-ATPases
      (SERCAs) in vitro, but its function in vivo has not been defined. NF-SLN cDNA
      (SLN tagged N-terminally with a FLAG epitope) was introduced into rat soleus
      muscle in one hindlimb by plasmid injection and electrotransfer. Western blotting
      showed expression and co-immunoprecipitation showed physical interaction between
      NF-SLN and SERCA2a. Contractile properties and SERCA2a function were assessed and
      compared with vector-injected contralateral soleus muscles. NF-SLN reduced both
      peak twitch force (P(t)) (123.9 +/- 12.5 versus 69.8 +/- 8.9 millinewtons) and
      tetanic force (P(o)) (562.3 +/- 51.0 versus 300.7 +/- 56.9 millinewtons) and
      reduced both twitch and tetanic rates of contraction (+dF/dt) and relaxation (
      dF/dt) significantly. Repetitive stimulation (750-ms trains at 50 Hz once every 2
      s for 3 min) showed that NF-SLN increased susceptibility to fatigue. These
      changes in contractile function were observed in the absence of endogenous
      phospholamban, and NF-SLN had no effect on either SERCA2a or SERCA1a expression
      levels. NF-SLN also decreased maximal Ca(2+) transport activity at pCa 5 by 31%
      with no significant change in apparent Ca(2+) affinity (6.36 +/- 0.07 versus 6.39
      +/- 0.08 pCa units). These results show that NF-SLN expression impairs muscle
      contractile function by inhibiting SERCA function and diminishing sarcoplasmic
      reticulum Ca(2+) stores.

PMID- 12237299
TI  - Interaction of the DnaK and DnaJ chaperone system with a native substrate, P1
      RepA.
AB  - DnaK, the Hsp70 chaperone of Escherichia coli interacts with protein substrates
      in an ATP-dependent manner, in conjunction with DnaJ and GrpE co-chaperones, to
      carry out protein folding, protein remodeling, and assembly and disassembly of
      multisubunit protein complexes. To understand how DnaJ targets specific proteins
      for recognition by the DnaK chaperone system, we investigated the interaction of
      DnaJ and DnaK with a known natural substrate, bacteriophage P1 RepA protein. By
      characterizing RepA deletion derivatives, we found that DnaJ interacts with a
      region of RepA located between amino acids 180 and 200 of the 286-amino acid
      protein. A peptide corresponding to amino acids 180-195 inhibited the interaction
      of RepA and DnaJ. Two site-directed RepA mutants with alanine substitutions in
      this region were about 4-fold less efficiently activated for oriP1 DNA binding by
      DnaJ and DnaK than wild type RepA. We also identified by deletion analysis a site
      in RepA, in the region of amino acids 35-49, which interacts with DnaK. An
      alanine substitution mutant in amino acids 36-39 was constructed and found
      defective in activation by DnaJ and DnaK. Taken together the results suggest that
      DnaJ and DnaK interact with separate sites on RepA.

PMID- 12237300
TI  - Lipopolysaccharide-induced methylation of HuR, an mRNA-stabilizing protein, by
      CARM1. Coactivator-associated arginine methyltransferase.
AB  - The RNA-binding protein HuR stabilizes labile mRNAs carrying AU-rich instability
      elements. This mRNA stabilization can be induced by hypoxia, lipopolysaccharide,
      and UV light. The mechanism by which these stimuli activate HuR is unclear and
      might be related to post-translational modification of this protein. Here we show
      that HuR can be methylated on arginine. However, HuR is not a substrate for
      PRMT1, the most prominent protein-arginine methyltransferase in mammalian cells,
      which methylates a number of heterogeneous nuclear ribonucleoproteins. Instead,
      HuR is specifically methylated by coactivator-associated arginine
      methyltransferase 1 (CARM1), a protein-arginine methyltransferase previously
      shown to serve as a transcriptional coactivator. By analyzing methylation of
      specific HuR arginine-to-lysine mutants and by sequencing radioactively
      methylated HuR peptides, Arg(217) was identified as the major HuR methylation
      site. Arg(217) is located in the hinge region between the second and third of the
      three HuR RNA recognition motif domains. Antibodies against a methylated HuR
      peptide were used to demonstrate in vivo methylation of HuR. HuR methylation
      increased in cells that overexpressed CARM1. Importantly, lipopolysaccharide
      stimulation of macrophages, which leads to HuR-mediated stabilization of tumor
      necrosis factor alpha mRNA in these cells, caused increased methylation of
      endogenous HuR. Thus, CARM1, which plays a role in transcriptional activation
      through histone H3 methylation, may also play a role in post-transcriptional gene
      regulation by methylating HuR.

PMID- 12237301
TI  - Laminin modulates morphogenic properties of the collagen XVIII endostatin domain.
AB  - We have shown previously that the oligomeric endostatin domain of collagen XVIII
      (NC1) functioned as a motility-inducing factor regulating the extracellular
      matrix-dependent morphogenesis of endothelial cells. This motogenic activity gave
      rise to structures resembling filipodia and lamellipodia and was dependent on
      Rac, Cdc42, and mitogen-activated protein kinase. Here, we demonstrate that these
      properties of endostatin are primarily mediated by laminin in the basement
      membrane and heparan sulfates on the cell surface. The sites of interaction
      between laminin and oligomeric endostain include the N-terminal regions of all
      three laminin chains (amino acids 204-1243 of the alpha chain, 932-1161 of the
      beta chain, and 150-965 of the gamma chain). A monoclonal antibody that blocks
      the interactions between endostatin and laminin was utilized to inhibit the
      motogenic activity of endostatin. In parallel, we have engineered selective point
      mutations and produced recombinant forms that lack binding to heparan sulfates on
      the cell surface. Our data are consistent with a model of endostatin with two
      binding sites: one mainly to laminin in the basement membrane and the other to
      heparan sulfates on the cell surface. The two binding domains on endostatin
      appear to be separate with the possibility of some overlap between the two sites.

PMID- 12237302
TI  - Rat encodes the paralogous gene equivalent of the human histo-blood group ABO
      gene. Association with antigen expression by overexpression of human ABO
      transferase.
AB  - We cloned a rat ABO homologue and established human A- and B-transferase
      transgenic rats. A DNA fragment corresponding to exon 7 of the human ABO gene was
      amplified from Wistar rat genomic DNA and sequenced. Using the amplified
      fragments as a probe for Southern blotting, multiple hybridized bands appeared on
      both EcoRI- and BamHI-digested genomes of seven rat strains, which showed
      variations in the band numbers among the strains. Four cDNAs were cloned from a
      Wistar rat, three of which showed A-transferase activity and one of which showed
      B-transferase activity. These activities were dependent on the equivalent
      residues at 266 and 268 of human ABO transferase. Wild Wistar rats expressed A
      antigen in salivary gland, intestine, and urinary bladder tissue, but B-antigen
      was not stained in any organs studied, whereas a transcript from the ABO
      homologue with B-transferase activity was ubiquitous. Human A-transferase and B
      transferase were transferred into Wistar rats. A-transgenic rats expressed A
      antigen in ectopic tissue of the brain plexus, type II lung epithelium, pancreas,
      and epidermis. B-antigen in the B-transgenic rat was expressed in the same organs
      as A-transgenic rats. These results may shed light on the function and evolution
      of the ABO gene in primates.

PMID- 12237303
TI  - Functional analysis of the TFIID-specific yeast TAF4 (yTAF(II)48) reveals an
      unexpected organization of its histone-fold domain.
AB  - Yeast TFIID comprises the TATA binding protein and 14 TBP-associated factors
      (TAF(II)s), nine of which contain histone-fold domains (HFDs). The C-terminal
      region of the TFIID-specific yTAF4 (yTAF(II)48) containing the HFD shares strong
      sequence similarity with Drosophila (d)TAF4 (dTAF(II)110) and human TAF4
      (hTAF(II)135). A structure/function analysis of yTAF4 demonstrates that the HFD,
      a short conserved C-terminal domain (CCTD), and the region separating them are
      all required for yTAF4 function. Temperature-sensitive mutations in the yTAF4 HFD
      alpha2 helix or the CCTD can be suppressed upon overexpression of yTAF12
      (yTAF(II)68). Moreover, coexpression in Escherichia coli indicates direct yTAF4
      yTAF12 heterodimerization optimally requires both the yTAF4 HFD and CCTD. The x
      ray crystal structure of the orthologous hTAF4-hTAF12 histone-like heterodimer
      indicates that the alpha3 region within the predicted TAF4 HFD is unstructured
      and does not correspond to the bona fide alpha3 helix. Our functional and
      biochemical analysis of yTAF4, rather provides strong evidence that the HFD
      alpha3 helix of the TAF4 family lies within the CCTD. These results reveal an
      unexpected and novel HFD organization in which the alpha3 helix is separated from
      the alpha2 helix by an extended loop containing a conserved functional domain.

PMID- 12237304
TI  - Crystal structure of a subcomplex of human transcription factor TFIID formed by
      TATA binding protein-associated factors hTAF4 (hTAF(II)135) and hTAF12
      (hTAF(II)20).
AB  - The crystal structure is presented of a complex formed by the interacting domains
      from two subunits of the general transcription factor TFIID, the human TATA
      binding protein-associated factors hTAF4 (hTAF(II)135) and hTAF12 (hTAF(II)20).
      In agreement with predictions, hTAF12 forms a histone fold that is very similar
      to that of histone H2B, yet unexpected differences are observed between the
      structures of the hTAF12 interaction domain of hTAF4 and histone H2A. Most
      importantly, the hTAF4 fragment forms only the first two helices of a classical
      histone fold, which are followed by a 26-residue disordered region. This
      indicates that either full-length TAF4 contains an unusually long connecting loop
      between its second and third helix, and this helix is not required for stable
      interaction with TAF12, or that TAF4 represents a novel class of partial histone
      fold motifs. Structural models and structure-based sequence alignments support a
      role for TAF4b and hSTAF42/yADA1 as alternative partners for TAF12 and are
      consistent with the formation of nucleosome-like histone-fold octamers through
      interaction of TAF12 with a TAF6-TAF9 tetramer, yet argue against involvement of
      TAF12-containing histone-fold pairs in DNA binding.

PMID- 12237305
TI  - The endocannabinoid anandamide inhibits neuronal progenitor cell differentiation
      through attenuation of the Rap1/B-Raf/ERK pathway.
AB  - Endocannabinoids are neuromodulators that act as retrograde synaptic messengers
      inhibiting the release of different neurotransmitters in cerebral areas such as
      hippocampus, cortex, and striatum. However, little is known about other roles of
      the endocannabinoid system in brain. In the present work we provide substantial
      evidence that the endocannabinoid anandamide (AEA) regulates neuronal
      differentiation both in culture and in vivo. Thus AEA, through the CB(1)
      receptor, inhibited cortical neuron progenitor differentiation to mature neuronal
      phenotype. In addition, human neural stem cell differentiation and nerve growth
      factor-induced PC12 cell differentiation were also inhibited by cannabinoid
      challenge. AEA decreased PC12 neuronal-like generation via CB(1)-mediated
      inhibition of sustained extracellular signal-regulated kinase (ERK) activation,
      which is responsible for nerve growth factor action. AEA thus inhibited TrkA
      induced Rap1/B-Raf/ERK activation. Finally, immunohistochemical analyses by
      confocal microscopy revealed that adult neurogenesis in dentate gyrus was
      significantly decreased by the AEA analogue methanandamide and increased by the
      CB(1) antagonist SR141716. These data indicate that endocannabinoids inhibit
      neuronal progenitor cell differentiation through attenuation of the ERK pathway
      and suggest that they constitute a new physiological system involved in the
      regulation of neurogenesis.

PMID- 12237306
TI  - Synapsin I is phosphorylated at Ser603 by p21-activated kinases (PAKs) in vitro
      and in PC12 cells stimulated with bradykinin.
AB  - The function of synapsin I is regulated by phosphorylation of the molecule at
      multiple sites; among them, the Ser(603) residue (site 3) is considered to be a
      pivotal site targeted by Ca(2+)/calmodulin-dependent kinase II (CaMKII). Although
      phosphorylation of the Ser(603) residue responds to several kinds of stimuli, it
      is unlikely that many or all of the stimuli activate the CaMKII-involved pathway.
      Among the several stimulants tested in PC12 cells, bradykinin evoked the
      phosphorylation of Ser(603) without inducing the autophosphorylation of CaMKII,
      which was determined using phosphorylation site-specific antibodies against
      phospho-Ser(603)-synapsin I (pS603-Syn I-Ab) and phospho-Thr(286/287)-CaMKII. The
      bradykinin-evoked phosphorylation of Ser(603) was not suppressed by the CaMKII
      inhibitor KN62, whereas high KCl-evoked phosphorylation was accompanied by CaMKII
      autophosphorylation and inhibited by KN62. Thus, we attempted to identify
      Ser(603) kinase(s) besides CaMKII. We consequently detected four and three
      fractions with Ca(2+)/calmodulin-independent Ser(603) kinase activity on the DEAE
      column chromatography of bovine brain homogenate and PC12 cell lysate,
      respectively, two of which were purified and identified by amino acid sequence of
      proteolytic fragments as p21-activated kinase (PAK) 1 and PAK3. The
      immunoprecipitants from bovine brain homogenate with anti-PAK1 and PAK3
      antibodies incorporated (32)P into synapsin I in a Cdc42/GTPgammaS-dependent
      manner, and its phosphorylation site was confirmed as Ser(603) using pS603-Syn I
      Ab. Additionally, recombinant GST-PAK2 could phosphorylate the Ser(603) residue
      in the presence of Cdc42/GTPgammaS. Finally, we confirmed by immunocytochemical
      analysis that the transfection of constitutively active rat alphaPAK (PAK1) in
      PC12 cells evokes the phosphorylation of Ser(603) even in the resting mutant
      cells and enhances it in the bradykinin-stimulated cells, whereas that of
      dominant-negative alphaPAK quenches the phosphorylation. These results raise the
      possibility that Ser(603) on synapsin I is alternatively phosphorylated by PAKs,
      not only by CaMKII, in neuronal cells in response to some stimulants.

PMID- 12237307
TI  - Transforming growth factor-beta -Smad signaling pathway cooperates with NF-kappa
      B to mediate nontypeable Haemophilus influenzae-induced MUC2 mucin transcription.
AB  - Transforming growth factor-beta (TGF-beta) and related factors are
      multifunctional cytokines that regulate diverse cellular processes, including
      proliferation, differentiation, apoptosis, and immune response. The involvement
      of TGF-beta receptor-mediated signaling in bacteria-induced up-regulation of
      mucin, a primary innate defensive response for mammalian airways, however, still
      remains unknown. Here, we report that the bacterium nontypeable Haemophilus
      influenzae (NTHi), an important human respiratory pathogen, utilizes the TGF-beta
      Smad signaling pathway together with the TLR2-MyD88-TAK1-NIK-IKKbeta/gamma
      IkappaBalpha pathway to mediate NF-kappaB-dependent MUC2 mucin transcription. The
      NTHi-induced TGF-beta receptor Type II phosphorylation occurred at as early as 5
      min. Pretreatment of NTHi with TGF-beta neutralization antibody reduced up
      regulation of MUC2 transcription. Moreover, functional cooperation of NF-kappaB
      p65/p50 with Smad3/4 appears to positively mediate NF-kappaB-dependent MUC2
      transcription. These data are the first to demonstrate the involvement of TGF
      beta receptor-mediated signaling in bacteria-induced up-regulation of mucin
      transcription, bring insights into the novel role of TGF-beta signaling in
      bacterial pathogenesis, and may lead to new therapeutic intervention of NTHi
      infections.

PMID- 12237308
TI  - Oligomeric state and stoichiometry of p24 proteins in the early secretory
      pathway.
AB  - The p24 proteins belong to a highly conserved family of membrane proteins that
      cycle in the early secretory pathway. They bind to the coat proteins of COPI and
      COPII vesicles, and are proposed to be involved in vesicle biogenesis, cargo
      uptake, and quality control, but their precise function is still under debate.
      Most p24 proteins form hetero-oligomers, essential for their correct localization
      and stability. Functional insights regarding the mechanisms of their steady state
      localization and the role of interaction with coat proteins has been hampered by
      a lack of data on their concentration and state of oligomerization within the
      endoplasmic reticulum, the intermediate compartment, and Golgi complex. We have
      determined for all mammalian p24 family members the size of the oligomers formed
      and their stoichiometric relation in each of these individual organelles. In
      contrast to earlier reports, we show that individual members exist as dimers and
      monomers and that the ratio between these two forms depends on both the organelle
      investigated and the p24 protein. We find unequal quantities, with p23 and p27
      building up concentration gradients, ruling out a simple 1:1 stoichiometry. In
      addition, we show differential cycling of individual p24 members. These data
      point to a complex and dynamic system of altering dimerizations of the family
      members.

PMID- 12237309
TI  - Translational regulation of prostaglandin endoperoxide H synthase-1 mRNA in
      megakaryocytic MEG-01 cells. Specific protein binding to a conserved 20
      nucleotide CIS element in the 3'-untranslated region.
AB  - Prostaglandin endoperoxide H synthase-1 (PGHS-1) is an abundant enzyme in
      platelets, where it plays a key role in the cascade of prostanoid formation. In
      platelets, the primary site of PGHS-1 synthesis is in precursor megakaryocytic
      cells. We have previously shown that in megakaryocytic MEG-01 cells, TPA induces
      an increase of PGHS-1 mRNA within a few hours, whereas protein increase occurs
      after several days of treatment. We now report that the delayed increase in PGHS
      1 protein is caused by translational regulation. De novo PGHS-1 synthesis,
      measured using [(35)S]methionine pulse labeling followed by immunoprecipitation,
      was detected at day 4 after TPA treatment but not at day 1. To identify a
      potential element of PGHS-1 mRNA controlling translation, we compared the 3'
      untranslated region from different species and identified a 20-nt segment
      perfectly conserved. The 20-nt segment was used as a probe in RNA gel mobility
      shift assays using MEG-01 extracts from control cells or from TPA-treated cells.
      Four complexes were formed with extracts from control cells or cells treated with
      TPA for 1 day but were not observed with extracts from cells treated for 4 days.
      Of the 4 complexes, one was sequence-specific and binding involved uridylate
      residues and interactions with a 45-kDa protein and a protein doublet of 116 kDa.
      Binding of this 45/116-kDa complex to the 20-nt conserved cis element most likely
      regulates negatively PGHS-1 protein accumulation. We have provided evidence that
      the PGHS-1 gene is regulated at the translational level.

PMID- 12237310
TI  - The ClpB homolog Hsp78 is required for the efficient degradation of proteins in
      the mitochondrial matrix.
AB  - Molecular chaperones perform vital functions in mitochondrial protein import and
      folding. In yeast mitochondria, two members of the Clp/Hsp100 chaperone family,
      Hsp78 and Mcx1, have been identified as homologs of the bacterial proteins ClpB
      and ClpX, respectively. In this report we employed a novel quantitative assay
      system to assess the role of Hsp78 and Mcx1 in protein degradation within the
      matrix. Mitochondria were preloaded with large amounts of two purified
      recombinant reporter proteins exhibiting different folding stabilities.
      Proteolysis of the imported substrate proteins depended on the mitochondrial
      level of ATP and was mediated by the matrix protease Pim1/LON. Degradation rates
      were found to be independent of the folding stability of the reporter proteins.
      Mitochondria from hsp78Delta cells exhibited a significant defect in the
      degradation efficiency of both substrates even at low temperature whereas
      mcx1Delta mitochondria showed wild-type activity. The proteolysis defect in
      hsp78Delta mitochondria was independent from the aggregation behavior of the
      substrate proteins. We conclude that Hsp78 is a genuine component of the
      mitochondrial proteolysis system required for the efficient degradation of
      substrate proteins in the matrix.

PMID- 12237311
TI  - Topology of superoxide production from different sites in the mitochondrial
      electron transport chain.
AB  - We measured production of reactive oxygen species by intact mitochondria from rat
      skeletal muscle, heart, and liver under various experimental conditions. By using
      different substrates and inhibitors, we determined the sites of production (which
      complexes in the electron transport chain produced superoxide). By measuring
      hydrogen peroxide production in the absence and presence of exogenous superoxide
      dismutase, we established the topology of superoxide production (on which side of
      the mitochondrial inner membrane superoxide was produced). Mitochondria did not
      release measurable amounts of superoxide or hydrogen peroxide when respiring on
      complex I or complex II substrates. Mitochondria from skeletal muscle or heart
      generated significant amounts of superoxide from complex I when respiring on
      palmitoyl carnitine. They produced superoxide at considerable rates in the
      presence of various inhibitors of the electron transport chain. Complex I (and
      perhaps the fatty acid oxidation electron transfer flavoprotein and its
      oxidoreductase) released superoxide on the matrix side of the inner membrane,
      whereas center o of complex III released superoxide on the cytoplasmic side.
      These results do not support the idea that mitochondria produce considerable
      amounts of reactive oxygen species under physiological conditions. Our upper
      estimate of the proportion of electron flow giving rise to hydrogen peroxide with
      palmitoyl carnitine as substrate (0.15%) is more than an order of magnitude lower
      than commonly cited values. We observed no difference in the rate of hydrogen
      peroxide production between rat and pigeon heart mitochondria respiring on
      complex I substrates. However, when complex I was fully reduced using rotenone,
      rat mitochondria released significantly more hydrogen peroxide than pigeon
      mitochondria. This difference was solely due to an elevated concentration of
      complex I in rat compared with pigeon heart mitochondria.

PMID- 12237312
TI  - Single nucleotide polymorphism of the human high affinity choline transporter
      alters transport rate.
AB  - High affinity choline uptake plays a critical role in the regulation of
      acetylcholine synthesis in cholinergic neurons. Recently, we succeeded in
      molecular cloning of the high affinity choline transporter (CHT1), which is
      specifically expressed in cholinergic neurons. Here we demonstrate the presence
      of functionally relevant, nonsynonymous single nucleotide polymorphism in the
      human CHT1 gene by comprehensive sequence analysis of the exons and the
      intron/exon boundaries including the transcription start site. The deduced amino
      acid change for the polymorphism is isoleucine to valine at amino acid 89 (I89V)
      located within the third transmembrane domain of the protein. The allele
      frequency of I89V was 6% for Ashkenazi Jews. Functional assessment of the I89V
      transporter in mammalian cell lines revealed a 40-50% decrease in V(max) for
      choline uptake rate compared with the wild type, whereas there was no alteration
      in the apparent affinities for choline, sodium, chloride, and the specific
      inhibitor hemicholinum-3. There also was no change in the specific hemicholinum-3
      binding activity. The decreased choline uptake was not associated with the
      surface expression level of the protein as assessed by biotinylation assay. These
      results suggest an impaired substrate translocation in the I89V transporter. The
      Caenorhabditis elegans ortholog of CHT1 has a valine residue at the corresponding
      position and a single replacement from valine to isoleucine caused a decrease in
      the choline uptake rate by 40%, suggesting that this hydrophobic residue is
      generally critical in the choline transport rate in CHT1. This polymorphism in
      the allelic CHT1 gene may represent a predisposing factor for cholinergic
      dysfunction.

PMID- 12237313
TI  - Dose-dependent biphasic activity of tRNA synthetase-associating factor, p43, in
      angiogenesis.
AB  - Mammalian aminoacyl tRNA synthetases form a macromolecular protein complex with
      three non-enzymatic cofactors. Among these factors, p43 is also secreted to work
      as a cytokine on endothelial as well as immune cells. Here we investigated the
      activity of p43 in angiogenesis and determined the related mediators. It promoted
      the migration of endothelial cells at low dose but induced their apoptosis at
      high dose. p43 at low concentration activated extracellular signal-regulating
      kinase, which resulted in the induction and activation of matrix
      metalloproteinase 9. In contrast, p43 at high concentration activated Jun N
      terminal kinase, which mediated apoptosis of endothelial cells. These results
      suggest that p43 is a novel cytokine playing a dose-dependent biphasic role in
      angiogenesis.

PMID- 12237314
TI  - Rocaglamide derivatives are potent inhibitors of NF-kappa B activation in T
      cells.
AB  - Crude extracts from different Aglaia species are used as anti-inflammatory
      remedies in the traditional medicine of several countries from Southeast Asia.
      Because NF-kappaB transcription factors represent key regulators of genes
      involved in immune and inflammatory responses, we supposed that the anti
      inflammatory effects of Aglaia extracts are mediated by the inhibition of NF
      kappaB activity. Purified compounds of Aglaia species, namely 1H
      cyclopenta[b]benzofuran lignans of the rocaglamide type as well as one aglain
      congener were tested for their ability to inhibit NF-kappaB activity. We show
      that a group of rocaglamides represent highly potent and specific inhibitors of
      tumor necrosis factor-alpha (TNFalpha) and phorbol 12-myristate 13-acetate (PMA)
      induced NF-kappaB-dependent reporter gene activity in Jurkat T cells with IC(50)
      values in the nanomolar range. Some derivatives are less effective, and others
      are completely inactive. Rocaglamides are able to suppress the PMA-induced
      expression of NF-kappaB target genes and sensitize leukemic T cells to apoptosis
      induced by TNFalpha, cisplatin, and gamma-irradiation. The suppression of NF
      kappaB activation correlated with the inhibition of induced IkappaB(alpha)
      degradation and IkappaB(alpha) kinase activation. The level of interference was
      determined and found to be localized upstream of the IkappaB kinase complex but
      downstream of the TNF receptor-associated protein 2. Our data suggest that
      rocaglamide derivatives could serve as lead structures in the development of anti
      inflammatory and tumoricidal drugs.

PMID- 12237315
TI  - U0126 and PD98059, specific inhibitors of MEK, accelerate differentiation of
      RAW264.7 cells into osteoclast-like cells.
AB  - Osteoclasts are multinucleated cells that differentiate from hematopoietic cells
      and possess characteristics responsible for bone resorption. To study the
      involvement of mitogen-activated protein kinases (MAPKs) in osteoclastogenesis of
      the murine monocytic cell line RAW264.7, which can differentiate into osteoclast
      like cells in the presence of the receptor activator of nuclear factor kappa B
      ligand (RANKL), we treated the cells with specific inhibitors of p38 MAPK,
      PD169316 and SB203580, and specific inhibitors of MAPK extracellular signaling
      regulated kinase (ERK) kinase (MEK), U0126 and PD98059. Each inhibitor blocked
      differentiation into osteoclast-like cells when the cells were plated at the
      standard cell density (2000-4000 cells per well (96-well)). However, the effect
      of MEK inhibitors on osteoclastogenesis varied according to the initial cell
      density during culture, because cell growth was clearly inhibited by them. When
      the cells were plated at more than 8000 cells per well, marked enhancement and
      acceleration of the differentiation were observed. In addition, immunoblot
      analysis revealed that phosphorylation of ERK was increased by treatment with the
      p38 inhibitors, whereas the MEK inhibitors increased phosphorylation of p38,
      which implies a seesaw-like balance between ERK and p38 phosphorylation. We
      suggest that osteoclastogenesis is regulated under a balance between ERK and p38
      pathways and that the MEK/ERK pathway negatively regulates osteoclastogenesis
      while the p38 pathway does so positively. This is the first report that an
      inhibitor of signal transduction enhanced osteoclastogenesis.

PMID- 12237316
TI  - Pescadillo is essential for nucleolar assembly, ribosome biogenesis, and
      mammalian cell proliferation.
AB  - Mutation of the zebrafish pescadillo gene blocks expansion of a number of tissues
      in the developing embryo, suggesting roles for its gene product in controlling
      cell proliferation. We report that levels of the pescadillo protein increase in
      rodent hepatocytes as they enter the cell cycle. Pescadillo protein localizes to
      distinct substructures of the interphase nucleus including nucleoli, the site of
      ribosome biogenesis. During mitosis pescadillo closely associates with the
      periphery of metaphase chromosomes and by late anaphase is associated with
      nucleolus-derived foci and prenucleolar bodies. Blastomeres in mouse embryos
      lacking pescadillo arrest at morula stages of development, the nucleoli fail to
      differentiate and accumulation of ribosomes is inhibited. We propose that in
      mammalian cells pescadillo is essential for ribosome biogenesis and
      nucleologenesis and that disruption to its function results in cell cycle arrest.

PMID- 12237317
TI  - Mapping the type I collagen-binding site on pigment epithelium-derived factor.
      Implications for its antiangiogenic activity.
AB  - Pigment epithelium-derived factor (PEDF), a neurotrophic and antiangiogenic
      serpin, is identified in tissues rich in collagen, e.g. cornea, vitreous, bone,
      and cartilage. We show that recombinant human PEDF formed complexes with
      collagens from the bovine cornea and vitreous. We have examined the direct
      binding of PEDF to collagen I and found that interactions were ionic in nature
      and occurred when PEDF and collagen I were both in solution, when either one was
      immobilized, or even when collagen I was denatured under reducing conditions.
      (125)I-PEDF bound to immobilized collagen I in a saturable fashion (K(D) = 123
      nm). Compared with neurotrophic PEDF-derived peptides, ovalbumin and angiogenic
      inhibitors, only full-length PEDF competed efficiently with (125)I-PEDF for the
      binding to immobilized collagen I (EC(50) = 3 microg/ml). The collagen-binding
      region was analyzed using controlled proteolysis and chemically modified PEDF.
      Cleavage of the serpin exposed loop did not prevent binding to collagen I.
      Conjugation of lysines with fluorescein increased the collagen binding affinity.
      However, treatment of PEDF with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
      abolished it, implicating the PEDF aspartic and/or glutamic acid residues in its
      interaction with collagen I. A negatively charged region on the surface of the
      PEDF molecule is rich in acidic residues (Glu(41), Glu(42), Glu(43), Asp(44),
      Asp(64), Asp(256), Asp(258), Glu(290), Glu(291), Glu(296), Asp(300), Glu(304))
      available to interact directly with positively charged areas of collagen. This
      represents the first collagen-binding site described for a serpin, which in PEDF,
      is distinct from its heparin-binding region, neurotrophic active site, and its
      serpin exposed loop. The collagen-binding property of PEDF may play a role in
      surface localization and modulation of its antiangiogenic effects in the eye and
      bone.

PMID- 12237318
TI  - Functional consequences of insertions and deletions in the complementarity
      determining regions of human antibodies.
AB  - Insertions and deletions of nucleotides in the genes encoding the variable
      domains of antibodies are natural components of the hypermutation process, which
      may expand the available repertoire of hypervariable loop lengths and
      conformations. Although insertion of amino acids has also been utilized in
      antibody engineering, little is known about the functional consequences of such
      modifications. To investigate this further, we have introduced single-codon
      insertions and deletions as well as more complex modifications in the
      complementarity-determining regions of human antibody fragments with different
      specificities. Our results demonstrate that single amino acid insertions and
      deletions are generally well tolerated and permit production of stably folded
      proteins, often with retained antigen recognition, despite the fact that the thus
      modified loops carry amino acids that are disallowed at key residue positions in
      canonical loops of the corresponding length or are of a length not associated
      with a known canonical structure. We have thus shown that single-codon insertions
      and deletions can efficiently be utilized to expand structure and sequence space
      of the antigen-binding site beyond what is encoded by the germline gene
      repertoire.

PMID- 12237319
TI  - Mutations in human nonmuscle myosin IIA found in patients with May-Hegglin
      anomaly and Fechtner syndrome result in impaired enzymatic function.
AB  - A family of autosomal-dominant diseases including May-Hegglin anomaly, Fechtner
      syndrome, Sebastian syndrome, Alport syndrome, and Epstein syndrome are commonly
      characterized by giant platelets and thrombocytopenia. In addition, there may be
      leukocyte inclusions, deafness, cataracts, and nephritis, depending on the
      syndrome. Mutations in the human nonmuscle myosin IIA heavy chain gene (MYH9)
      have been linked to these diseases. Two of the recently described mutations, N93K
      and R702C, are conserved in smooth and nonmuscle myosins from vertebrates and lie
      in the head domain of myosin. Interestingly, the two mutations lie within close
      proximity in the three-dimensional structure of myosin. These two mutations were
      engineered into a heavy meromyosin-like recombinant fragment of nonmuscle myosin
      IIA, which was expressed in baculovirus along with the appropriate light chains.
      The R702C mutant displays 25% of the maximal MgATPase activity of wild type heavy
      meromyosin and moves actin filaments at half the wild type rate. The effects of
      the N93K mutation are more dramatic. This heavy meromyosin has only 4% of the
      maximal MgATPase activity of wild type and does not translocate actin filaments
      in an in vitro motility assay. Biochemical characterization of the mutant is
      consistent with this mutant being unable to fully adopt the "on" conformation.

PMID- 12237320
TI  - A new mechanism for anaerobic unsaturated fatty acid formation in Streptococcus
      pneumoniae.
AB  - The anaerobic pathway for unsaturated fatty acid synthesis was established in the
      1960s in Escherichia coli. The double bond is introduced into the growing acyl
      chain by FabA, an enzyme capable of both the dehydration of beta-hydroxydecanoyl
      acyl carrier protein (ACP) to trans-2-decenoyl-ACP, and the isomerization of
      trans-2 to cis-3-decenoyl-ACP. However, there are a number of anaerobic bacteria
      whose genomes do not contain a fabA homolog, although these organisms nonetheless
      produce unsaturated fatty acids. We cloned and biochemically characterized a new
      enzyme in type II fatty acid synthesis from Streptococcus pneumoniae that carries
      out the isomerization of trans-2-decenoyl-ACP to cis-3-decenoyl-ACP, but is not
      capable of catalyzing the dehydration of beta-hydroxy intermediates. This
      tetrameric enzyme, designated FabM, has no similarity to FabA, but rather is a
      member of the hydratase/isomerase superfamily. Thus, the branch point in the
      biosynthesis of unsaturated fatty acids in S. pneumoniae occurs following the
      formation of trans-2-decenoyl-ACP, in contrast to E. coli where the branch point
      takes place after the formation of beta-hydroxydecanoyl-ACP.

PMID- 12237321
TI  - Prostaglandin E2 promotes integrin alpha Vbeta 3-dependent endothelial cell
      adhesion, rac-activation, and spreading through cAMP/PKA-dependent signaling.
AB  - We have recently reported that the inhibition of endothelial cell COX-2 by non
      steroidal anti-inflammatory drugs suppresses alpha(V)beta(3)- (but not
      alpha(5)beta(1)-) dependent Rac activation, endothelial cell spreading,
      migration, and angiogenesis (Dormond, O., Foletti, A., Paroz, C., and Ruegg, C.
      (2001) Nat. Med. 7, 1041-1047). Here we investigated the role of the COX-2
      metabolites PGE(2) and TXA2 in regulating human umbilical vein endothelial cell
      (HUVEC) adhesion and spreading. We report that PGE(2) accelerated alpha(V)beta(3)
      mediated HUVEC adhesion and promoted Rac activation and cell spreading, whereas
      the TXA2 agonist retarded adhesion and inhibited spreading. We show that the cAMP
      level and the cAMP-regulated protein kinase A (PKA) activity are critical
      mediators of these PGE(2) effects. alpha(V)beta(3)-mediated adhesion induced a
      transient COX-2-dependent rise in cAMP levels, whereas the cell-permeable cAMP
      analogue 8-brcAMP accelerated adhesion, promoted Rac activation, and cell
      spreading in the presence of the COX-2 inhibitor NS-398. Pharmacological
      inhibition of PKA completely blocked alpha(V)beta(3)-mediated adhesion. A
      constitutively active Rac mutant (L61Rac) rescued alpha(V)beta(3)-dependent
      spreading in the presence of NS398 or, but did not accelerate adhesion, whereas a
      dominant negative Rac mutant (N17Rac) suppressed spreading without affecting
      adhesion. alpha(5)beta(1)-mediated HUVEC adhesion, Rac activation, and spreading
      were not affected by PGE(2), 8-brcAMP, or the inhibition of PKA. In conclusion,
      these results demonstrate that PGE(2) accelerates alpha(V)beta(3)-mediated
      endothelial cell adhesion through cAMP-dependent PKA activation and induces
      alpha(V)beta(3)-dependent spreading via cAMP- and PKA-dependent Rac activation
      and may contribute to the further understanding of the regulation of vascular
      integrins alpha(V)beta(3) by COX-2/PGE(2) during tumor angiogenesis and
      inflammation.

PMID- 12237322
TI  - Inhibition of bcl-x(l) phosphorylation by tea polyphenols or epigallocatechin-3
      gallate is associated with prostate cancer cell apoptosis.
AB  - Prostate cancer cells demonstrate slow growth kinetics and chemoresistance. Tea
      polyphenols have been shown to exert prostate cancer-preventative effects. Here
      we report that growth-arrested prostate cancer cells expressed high levels of a
      hyperphosphorylated Bcl-X(L) in mitochondria. Treatment with tea polyphenols or
      the major tea component epigallocatechin-3-gallate blocked expression of the
      hyper-, but not hypophosphorylated Bcl-X(L) in mitochondria, accompanied by
      cytochrome c release, caspase activation, and apoptosis. Studies using specific
      inhibitors suggest that tea inhibits p38 mitogen-activated protein kinase and the
      proteasome activities, leading to inhibition of Bcl-X(L) phosphorylation and
      induction of prostate cancer cell death.

PMID- 12237323
TI  - Resveratrol suppresses angiotensin II-induced Akt/protein kinase B and p70 S6
      kinase phosphorylation and subsequent hypertrophy in rat aortic smooth muscle
      cells.
AB  - Resveratrol (RV), a polyphenolic substance found in grape skin, is proposed to
      account in part for the protective effect of red wine in the cardiovascular
      system. Angiotensin II (Ang II)-induced hypertrophy of vascular smooth muscle
      cells (VSMCs) is a pivotal step in the development of cardiovascular disease. The
      aims of this study were to test the hypothesis that RV may alter Ang II-mediated
      hypertrophic VSMC growth and to identify the putative underlying signaling
      pathways. We show that RV indeed potently inhibits Ang II-induced [(3)H]leucine
      incorporation in a concentration-dependent manner (50 microM RV, 71% inhibition).
      Western blot analysis reveals that phosphorylation of Akt/protein kinase B (PKB)
      and to a lesser extent the mitogen-activated protein kinase extracellular signal
      regulated kinase (ERK) 1/2, both essentially involved in Ang II-mediated
      hypertrophy, is dose dependently reduced by RV. Consistent with these results, we
      show that RV attenuates phosphorylation of the p70 ribosomal protein S6 kinase
      (p70(S6K)), a kinase downstream of the ERK 1/2 as well as the Akt pathway, that
      is implicated in Ang II-induced protein synthesis. Upstream of Akt/PKB RV seems
      to mediate its antihypertrophic effect by inhibiting phosphorylation of the
      phosphatidylinositol 3-kinase (PI(3)K) rather than by activating phosphatases. In
      summary, we demonstrate for the first time that RV inhibits Ang II-induced VSMC
      hypertrophy, possibly by interfering mainly with the PI(3)K/Akt and p70(S6K) but
      also with the ERK 1/2 signaling pathway. Thus, this study delivers important new
      insight in the molecular pathways that may contribute to the proposed beneficial
      effects of RV in cardiovascular disease.

PMID- 12237324
TI  - Conformation of ligands bound to the muscarinic acetylcholine receptor.
AB  - Many biogenic amines evoke a variety of physiological responses by acting on G
      protein-coupled receptors. We have determined the conformation of two
      acetylcholine analogs, (S)-methacholine and (2S,4R,5S)-muscarine, bound to the
      M(2) muscarinic acetylcholine receptor (M(2) mAChR) by NMR spectroscopy. The
      analysis of the transferred nuclear Overhauser effect indicated that the receptor
      selectively recognized the conformers of (S)-methacholine and (2S,4R,5S)
      muscarine with the gauche O-C2-C1-N dihedral angle at +60 degrees. This is
      distinct from the predominant conformations of these ligands in solution with O
      C2-C1-N dihedral angle (+80 to approximately 85 degrees ) in the absence of the
      M(2) mAChR, as assessed by analyses of the coupling constants and nuclear
      Overhauser effect spectroscopy. We have also built a molecular model of the M(2)
      mAChR-(S)-methacholine complex, based on the X-ray crystallographic structure of
      rhodopsin. This model indicated that the conformation with the gauche O-C2-C1-N
      dihedral angle at +55.5 degrees, which is similar to the one determined by NMR
      measurement, is energetically favored in the binding of (S)-methacholine to the
      receptor. We suggest that this conformation represents the binding of the agonist
      to the M(2) mAChR in the absence of G protein.

PMID- 12237325
TI  - Structurally and functionally important amino acids of the agonistic conformation
      of the human vitamin D receptor.
AB  - The crystal structures of the ligand binding domain of human vitamin D receptor
      (VDR) complexed with its natural ligand or the superagonists MC1288 or KH1060
      have recently been reported. The crystallized ligand binding domain (LBD) of VDR,
      however, differs from the full-length VDR with respect to deletion of 50 amino
      acids between its helices 2 and 3. In this study, we investigated structurally
      and functionally important amino acid interactions within the ligand binding
      pocket of the full-length VDR in the presence of several synthetic vitamin D(3)
      analogs. We used site-directed mutagenesis scanning combined with limited
      proteolytic digestion, electrophoretic mobility shift assay, and reporter gene
      assay and correlated the findings with the crystal structures of truncated VDR
      LBD. Our results suggest that structurally different agonists have distinct
      ligand-receptor interactions and that the amino acid residues H229, D232, E269,
      F279, and Y295 are critical for the agonistic conformation of the VDR. Our
      biological data, which were obtained with the full-length VDR, fit well with the
      crystal structure of the truncated VDR LBD and suggest that removal of the
      insertion domain between helices 2 and 3 of the receptor does not markedly
      influence the functionality of the VDR.

PMID- 12237326
TI  - Kinetics and crystal structure of catechol-o-methyltransferase complex with co
      substrate and a novel inhibitor with potential therapeutic application.
AB  - Catechol-O-methyltransferase (COMT; E.C. 2.1.1.6) is a ubiquitous enzyme in
      nature that plays an important role in the metabolism of catechol
      neurotransmitters and xenobiotics. In particular, inactivation of drugs such as L
      3,4-dihydroxyphenylalanine (L-DOPA) via O-methylation is of relevant
      pharmacological importance, because L-DOPA is currently the most effective drug
      used in the treatment of Parkinson's disease. This justified the interest in
      developing COMT inhibitors as potential adjuncts to L-DOPA therapy. The kinetics
      of inhibition by BIA 3-335 (1-[3,4-dihydroxy-5-nitrophenyl]-3-(N-3'
      trifluormethylphenyl)-piperazine-1-propanone dihydrochloride) were characterized
      using recombinant rat soluble COMT. BIA 3-335 was found to act as a potent,
      reversible, tight-binding inhibitor of COMT with a K(i) of 6.0 +/- 1.6 nM and
      displaying a competitive inhibition toward the substrate binding site and
      uncompetitive inhibition toward the S-adenosyl-L-methionine (SAM) binding site.
      The 2.0-A resolution crystal structure of COMT in complex with its cosubstrate
      SAM and a novel inhibitor BIA 3-335 shows the atomic interactions between the
      important residues at the active site and the inhibitor. This is the first report
      of a three-dimensional structure determination of COMT complexed with a potent,
      reversible, and tight-binding inhibitor that is expected to have therapeutic
      applications.

PMID- 12237327
TI  - Ligand-dependent and independent modulation of aryl hydrocarbon receptor
      localization, degradation, and gene regulation.
AB  - Changes in the concentration or subcellular location of the key proteins involved
      in signal transduction pathways have been shown to impact gene regulation.
      Studies were designed to evaluate the relationship between aryl hydrocarbon
      receptor (AHR) localization, stability, and gene regulation in a defined system
      where the endogenous AHR protein could be evaluated. The findings indicate that
      treatment of cells with geldanamycin (GA) or MG-132 (an inhibitor of the 26S
      proteasome) results in nuclear translocation of the endogenous AHR in both human
      HepG2 and murine Hepa-1 cells without induction of endogenous CYP1A1 protein.
      Exposure to GA resulted in the degradation of AHR by >90% in the nucleus via the
      26S proteasome. Importantly, the reduced level of AHR resulted in a 50% reduction
      in the maximal level of CYP1A1 induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD). In all treatments the concentration of the AHR nuclear translocator
      (ARNT) protein was unchanged and had no impact on the localization of the AHR.
      Thus, ligand-independent translocation of the AHR to the nucleus was not
      sufficient to induce CYP1A1 in the absence of ligand, but reductions in the level
      of the endogenous AHR protein pool shifted the dose-response curve for TCDD to
      the right.

PMID- 12237328
TI  - Desensitization of homomeric alpha1 glycine receptor increases with receptor
      density.
AB  - Variations in the number of receptors at glycinergic synapses are now established
      and are believed to contribute to inhibitory synaptic plasticity. However, the
      relation between glycine receptor (GlyR) kinetics and density is still unclear.
      We used outside-out patch-clamp recordings and fast-flow application techniques
      to resolve fast homomeric GlyRalpha1 kinetics and to determine how the functional
      properties of these receptors depend on their density and on the presence of the
      anchoring protein gephyrin. The expression of GlyRs in human embryonic kidney
      cells increased with time and was correlated with an increase in GlyR
      desensitization at 2 days after transfection. Cotransfection of homomeric
      GlyRalpha1 bearing the gephyrin-binding site with gephyrin also increased
      desensitization but at 1 day after transfection compared with transfections of
      homomeric GlyRalpha1 without gephyrin. This increase results from the occurrence
      of a fast desensitization component and short applications of a saturating
      concentration of glycine suffice to promote a rapidly entered desensitized closed
      state. The level of desensitization changed neither the EC(50) value nor the Hill
      coefficient of the glycine dose-response curves because the amplitude of the
      current was measured at the peak of the responses. These results demonstrate that
      variations in GlyR density during cluster formation result from a change in GlyR
      efficiency due to modifications in their desensitization properties.

PMID- 12237329
TI  - DNA microarray analysis of cannabinoid signaling in mouse brain in vivo.
AB  - To identify novel genes involved in cannabinoid receptor-mediated signaling, we
      used cDNA microarrays to detect changes in mRNA expression in the forebrains of
      mice 12 h after they were given a single intraperitoneal dose of the naturally
      occurring Cannabis sativa alkaloid Delta(9)-tetrahydrocannabinol (Delta(9)-THC)
      or the synthetic cannabinoid receptor agonist (R)-(+)-2,3-dihydro-5-methyl-3
      [(morpholinyl)methyl] pyrrolo[1,2,3-de]-1,4-benzoxazin-yl-1-naphtalenylmethanone
      mesylate [R(+)-WIN 55,212-2]. Of approximately 11,000 genes from a mouse brain
      cDNA library that were probed, 65 showed altered (increased or decreased at least
      2-fold) expression after exposure to Delta(9)-THC, 41 after exposure to R(+)-WIN
      55,212-2, and 20 genes after exposure to both drugs. Genes affected similarly by
      Delta(9)-THC and R(+)-WIN 55,212-2 were considered likely to reflect cannabinoid
      receptor activation, and expression of the protein products of two such genes not
      previously implicated in cannabinoid signaling-melanocyte-specific gene-related
      gene 1 (MRG1) and hexokinase 4 (glucokinase, GK)-was measured by Western blotting
      and immunohistochemistry. Western blots showed approximately 2-fold increases in
      the levels of both proteins in mouse forebrain. Immunohistochemistry revealed
      preferential localization of MRG1 to cerebral blood vessels and of GK to
      hypothalamic neurons. These findings suggest that MRG1 and GK are cannabinoid
      regulated genes and that they may be involved in the vascular and hypothalamic
      effects of cannabinoids, respectively.

PMID- 12237330
TI  - Molecular basis of pimarane compounds as novel activators of large-conductance
      Ca(2+)-activated K(+) channel alpha-subunit.
AB  - Effects of pimaric acid (PiMA) and eight closely related compounds on large
      conductance K(+) (BK) channels were examined using human embryonic kidney (HEK)
      293 cells, in which either the alpha subunit of BK channel (HEKBKalpha) or both
      alpha and beta1 (HEKBKalphabeta1) subunits were heterologously expressed. Effects
      of these compounds (10 microM) on the membrane potential of HEKBKalphabeta1 were
      monitored by use of DiBAC(4)(3), a voltage-sensitive dye. PiMA, isopimaric acid,
      sandaracoisopimaric acid, dihydropimaric acid, dihydroisopimaric acid, and
      dihydroisopimarinol induced substantial membrane hyperpolarization. The direct
      measurement of BKalphabeta1 opening under whole-cell voltage clamp showed that
      these six compounds activated BKalphabeta1 in a very similar concentration range
      (1-10 microM); in contrast, abietic acid, sclareol, and methyl pimarate had no
      effect. PiMA did not affect the charybdotoxin-induced block of macroscopic
      BKalphabeta1 current. Single channel recordings of BKalphabeta1 in inside-out
      patches showed that 10 microM PiMA did not change channel conductance but
      significantly increased its open probability as a result of increase in
      sensitivity to Ca(2+) and voltage. Because coexpression of the beta1 subunit did
      not affect PiMA-induced potentiation, the site of action for PiMA is suggested to
      be BKalpha subunit. PiMA was selective to BK over cloned small and intermediate
      Ca(2+) activated K(+) channels. In conclusion, PiMA (>1 microM) increases Ca(2+)
      and voltage-sensitivity of BKalpha when applied from either side of the cell
      membrane. The marked difference in potency as BK channel openers between PiMA and
      abietic acid, despite only very small differences in their chemical structures,
      may provide insight into the fundamental structure-activity relationship
      governing BKalpha activation.

PMID- 12237331
TI  - Down-regulation of cell surface insulin receptor and insulin receptor substrate-1
      phosphorylation by inhibitor of 90-kDa heat-shock protein family: endoplasmic
      reticulum retention of monomeric insulin receptor precursor with calnexin in
      adrenal chromaffin cells.
AB  - Treatment (>/=6 h) of cultured bovine adrenal chromaffin cells with geldanamycin
      (GA) or herbimycin A (HA), an inhibitor of the 90-kDa heat-shock protein (Hsp90)
      family, decreased cell surface (125)I-insulin binding. The effect of GA was
      concentration (EC(50) = 84 nM)- and time (t(1/2) = 8.5 h)-dependent; GA (1 microM
      for 24 h) lowered the B(max) value of (125)I-insulin binding by 80%, without
      changing the K(d) value. Western blot analysis showed that GA (>/=3 h) lowered
      insulin receptor (IR) level by 83% (t(1/2) = 7.4 h; EC(50) = 74 nM), while
      raising IR precursor level by 100% (t(1/2) = 7.9 h; EC(50) = 300 nM). Pulse-label
      followed by reducing and nonreducing sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis revealed that monomeric IR precursor (~190 kDa) developed into
      the homodimeric IR precursor (approximately 380 kDa) and the mature
      alpha(2)beta(2) IR (~410 kDa) in nontreated cells, but not in GA-treated cells;
      in GA-treated cells, the homodimerization-incompetent form of monomeric IR
      precursor was degraded via endoplasmic reticulum (ER)-associated protein
      degradation. Immunoprecipitation followed by immunoblot analysis showed that IR
      precursor was associated with calnexin (CNX) to a greater extent in GA-treated
      cells, compared with nontreated cells. GA had no effect on IR mRNA levels and
      internalization rate of cell surface IRs. In GA-treated cells, insulin-induced
      tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) was attenuated
      by 77%, with no change in IRS-1 level. Thus, inhibition of the Hsp90 family by GA
      or HA interrupts homodimerization of monomeric IR precursor in the ER and
      increases retention of monomeric IR precursor with CNX; this event retards cell
      surface expression of IR and attenuates insulin-induced activation of IRS-1.

PMID- 12237332
TI  - Tranilast inhibits cytokine-induced nuclear factor kappaB activation in vascular
      endothelial cells.
AB  - Tranilast [N-(3,4-dimethoxycinnamoyl)anthranilic acid] inhibits vascular
      inflammation. However, the relevant anti-inflammatory mechanisms are not
      completely understood. We studied the effects of tranilast on nuclear factor
      kappaB (NF-kappaB)-dependent endothelial cell adhesion molecule expression and
      transcriptional regulation. Cultured human umbilical vein endothelial cells were
      preincubated with 12.5 to 100 microg/ml tranilast. Tumor necrosis factor-alpha
      (TNF-alpha)-induced endothelial VCAM-1, ICAM-1, and E-selectin surface expression
      was inhibited dose dependently. Maximal inhibition achieved with 100 microg/ml
      tranilast was 38 +/- 6.9, 31.8 +/- 1.5, and 31.9 +/- 1.9%, respectively (mean +/-
      S.E.M., p < 0.001, n = 5). Secretion of interleukin 6, which is also NF-kappaB
      sensitive, was significantly inhibited by tranilast. Endothelial MHC-I
      expression, which is independent of NF-kappaB, was not inhibited. Although
      cytokine-induced degradation of NF-kappaB inhibitor proteins (IkappaB-alpha, 
      beta, and -epsilon), nuclear translocation of NF-kappaB, and binding of NF-kappaB
      to kappaB cis-acting elements in the adhesion molecule promoters were not
      affected by tranilast, ICAM-1-kappaB and E-selectin-kappaB reporter gene activity
      was inhibited by 53% (n = 5, p < 0.01) and 51% (n = 5, p < 0.001), respectively.
      In contrast, using SP-1 and C/EBP constructs, reporter gene activity was not
      altered. Expression of the transcriptional coactivator cAMP response element
      binding protein binding protein (CBP) was inhibited by tranilast, resulting in a
      loss of interaction between NF-kappaB and CBP. Therefore, in therapeutically
      relevant concentrations (50 microg/ml), tranilast inhibits NF-kappaB-dependent
      transcriptional activation by interfering with the NF-kappaB/CBP association. We
      propose that inhibition of NF-kappaB dependent gene transcription contributes to
      the anti-inflammatory effects of tranilast.

PMID- 12237333
TI  - Translocation of liposomes into cancer cells by cell-penetrating peptides
      penetratin and tat: a kinetic and efficacy study.
AB  - Unlike conventional liposomes, sterically stabilized liposomes, with their
      smaller volume of distribution and reduced clearance, preferentially convey
      encapsulated drugs into tumor sites. Despite these improvements, intracellular
      delivery is hampered by the stable drug retention of the liposomes, which
      diminishes the efficacy of the liposomal drug. To facilitate uptake of liposomal
      drugs into cells, two cell-penetrating peptides, penetratin (PEN) and TAT,
      derived from the HIV-1 TAT protein, were studied. In contrast to control
      peptides, both TAT and PEN enhanced the translocation efficiency of liposomes in
      proportion to the number of peptides attached to the liposomal surface. A peptide
      number of as few as five could enhance the intracellular delivery of liposomes.
      The kinetics of uptake was peptide- and cell-type dependent. Intracellular
      accumulation of TAT-liposomes increased with incubation time, but PEN-liposomes
      peaked at 1 h and then declined gradually. After treatment with 1 microg/ml
      doxorubicin equivalents of liposome for 2 h, TAT increased the doxorubicin uptake
      of A431 cells by 12-fold. However, the improvement of uptake of liposomal
      doxorubicin was not reflected by cytotoxicity in vitro or tumor control in vivo.
      Our results demonstrated that merely adding CPP to a liposome encapsulating
      anticancer drug was inadequate in improving its antitumor activity. An additional
      approach to enhance the intracellular release of the encapsulated drug is
      obviously necessary.

PMID- 12237334
TI  - Inhibition of DNA topoisomerases II and/or I by pyrazolo[1,5-a]indole derivatives
      and their growth inhibitory activities.
AB  - DNA topoisomerases (topos) I and II are molecular targets of several potent
      anticancer agents. Thus inhibitors of these enzymes are potential candidates or
      model compounds for anticancer drugs. We found some of the totally synthetic
      pyrazolo[1,5-a]indole derivatives, GS-2, -3, and -4, to be strong inhibitors of
      topo II, and GS-5 was found to be a dual inhibitor of topos I and II (IC(50)
      values were in the range of 10-30 microM). Because of the DNA-intercalating
      activity of these compounds affecting supercoil structure of closed circular DNA,
      the method of evaluation of topo I inhibition designed for such compounds by
      Pommier et al. (Nucleic Acids Res 15:6713-6731, 1987) was employed. Results
      showed that only GS-5 with a hydroxyl group at position C-6 was found to be a
      strong inhibitor of topo I with an IC(50) of approximately 10 microM. Inhibition
      of topo I and/or topo II by these compounds does not involve significant
      accumulation of DNA-topo I/II cleavable complexes, demonstrating that they are
      not topo poisons but catalytic inhibitors. In the "band depletion" analysis for
      in vivo targeting of topo I and II, these compounds were shown to suppress
      depletion of intracellular free enzymes by the topo poisons etoposide and/or
      camptothecin, indicating that they do target topo I and/or II in living cells.
      These compounds also exhibit moderate to strong growth-inhibitory activity in
      panels of human cancer cell lines. This study shows pyrazolo[1,5-a]indole
      derivatives to be a novel group of anticancer chemotherapeutic agents with single
      or dual catalytic inhibitory activities against topo I and topo II.

PMID- 12237335
TI  - Regulation of mouse kappa opioid receptor gene expression by different 3'
      untranslated regions and the effect of retinoic acid.
AB  - The mouse kappa opioid receptor (KOR) gene uses two functional polyadenylation
      signals, separated by a distance of approximately 2.2 kilobases (kb) in the 3'
      end of the gene. As a result, two major groups of KOR transcripts, with sizes of
      approximately 1.6 and 3.8 kb, respectively, are detected in mouse tissues and P19
      cells. Utilization of different poly(A) of the KOR gene produces KOR transcripts
      of different mRNA stability, transcription efficiency, and regulatability.
      Retinoic acid specifically suppresses the expression of KOR transcripts using the
      second poly(A) in P19 cells. A putative transcriptional enhancer region is
      present within the second 3'-untranslated region (3'-UTR). It is concluded that
      alternative polyadenylation of the mouse KOR transcripts results in differential
      regulation of KOR expression at both transcriptional and post-transcriptional
      levels. A negative regulatory pathway for KOR transcription involves a putative
      enhancer region in its 3'-UTR. KOR mRNAs using the second poly(A) is more stable
      than that using the first poly(A).

PMID- 12237336
TI  - Unexpected anthracycline-mediated alterations in iron-regulatory protein-RNA
      binding activity: the iron and copper complexes of anthracyclines decrease RNA
      binding activity.
AB  - Anthracyclines are effective antineoplastic agents. However, the interaction of
      these drugs with iron (Fe) is an important cause of myocardial toxicity, limiting
      their therapeutic use (J Lab Clin Med 122:245-251, 1993). To overcome this
      limitation, it is crucial to understand how anthracyclines interact with the Fe
      metabolism of myocardial and neoplastic cells. Iron-regulatory proteins (IRPs)
      play vital roles in regulating cellular Fe metabolism via their mRNA-binding
      activity. We showed that doxorubicin (DOX) and its analogs interfere with tumor
      and myocardial cell Fe metabolism by affecting the RNA-binding activity of IRPs.
      Unexpectedly, experiments with the free radical scavengers, catalase, superoxide
      dismutase, ebselen, and Mn(III) tetrakis (4-benzoic acid) porphyrin complex,
      suggested that the effects of DOX on IRP-RNA-binding activity were not due to
      anthracycline-mediated free radical production. In contrast to previous studies,
      we showed that the DOX metabolite, doxorubicinol, had no effect on IRP-RNA
      binding activity. Rather, the anthracycline-Fe and -copper (Cu) complexes
      decreased IRP-RNA-binding activity, indicating that formation of anthracycline
      metal complexes may affect cellular Fe metabolism. In addition, anthracyclines
      prevented the response of IRPs to the depletion of intracellular Fe by chelators.
      This information may be useful in designing novel therapeutic strategies against
      tumor cells by combining chelators and anthracyclines. Interestingly, the effect
      of DOX on primary cultures of cardiomyocytes was similar to that observed using
      neoplastic cells, and particularly notable was the decrease in IRP2-RNA-binding
      activity. Our results add significant new information regarding the effects of
      anthracyclines on Fe metabolism that may lead to the design of more effective
      treatments.

PMID- 12237337
TI  - Regulation of the neuronal glutamate transporter excitatory amino acid carrier-1
      (EAAC1) by different protein kinase C subtypes.
AB  - In previous studies, we have shown that activation of protein kinase C (PKC)
      rapidly (within minutes) increases the activity and cell surface expression of
      the glutamate transporter EAAC1 in two systems that endogenously express this
      transporter (C6 glioma cells and cocultures of neurons and astrocytes). However,
      the magnitude of the increase in activity is greater than the increase in cell
      surface expression. In addition, certain compounds completely block the increase
      in cell surface expression but only partially attenuate the increase in activity.
      We hypothesized that PKC increases EAAC1 activity by increasing cell surface
      expression and catalytic efficiency and that two different subtypes of PKC
      mediate these effects. To address these hypotheses, the PKC subtypes expressed by
      C6 glioma cells were identified. Of the PKC subtypes that are activated by
      phorbol esters, only PKCalpha, PKCdelta, and PKCepsilon were observed. Go6976, a
      compound that blocks PKCalpha at concentrations that do not inhibit PKCdelta or
      PKCepsilon, partially inhibited the increase in uptake but completely abolished
      the increase in EAAC1 cell surface expression. The 'Go6976-insensitive' increase
      in activity was not associated with a change in total transporter expression but
      was associated with an increase in the V(max). Na(+)-dependent glycine transport
      was not increased, providing indirect evidence that the Go6976-insensitive
      increase in activity was not caused by a change in the Na(+) electrochemical
      gradient required for activity. Finally, by down-regulating different subtypes of
      PKC, we found evidence that PKCepsilon mediates the increase in EAAC1 activity
      that is independent of changes in cell surface expression and found further
      evidence that PKCalpha mediates the increase in cell surface expression. The
      potential relationship of the present work with a previously identified role for
      PKCalpha in certain forms of synaptic plasticity is discussed.

PMID- 12237338
TI  - Selective estrogen receptor (ER) modulators differentially regulate phospholipase
      D catalytic activity in ER-negative breast cancer cells.
AB  - Recent successes in the pharmacotherapeutic treatment of breast cancer are
      associated with the use of selective estrogen receptor modulators. Two commonly
      prescribed pharmaceuticals in this class, tamoxifen and raloxifene, have been
      shown to have effects through estrogen receptor (ER)-independent mechanisms.
      Hyperactivation of phospholipase D (PLD) in certain tumor-derived cell lines have
      been reported, and recent findings suggest a role for PLD in transformation and
      metastasis. In the present study, we compare the effects of tamoxifen and
      raloxifene on PLD in the ER-positive mammary epithelial cell line MCF-12A, and
      the ER-negative, highly tumorigenic mammary carcinoma cell line MDA-MB-231. Our
      data demonstrate that tamoxifen and raloxifene have differential effects on PLD
      catalytic activity. Tamoxifen stimulates PLD in both ER-positive and -negative
      cells in vivo, whereas raloxifene inhibits PLD activity in these same cell types.
      In addition, we show that the active metabolite 4-OH-tamoxifen can be used to
      pharmacologically discriminate the two isoforms of PLD, through a stimulatory
      effect on PLD1 and an inhibitory effect on PLD2. Using recombinant PLD1, we show
      stimulation by tamoxifen requires a factor present in Sf21 insect cells that is
      not required for inhibition of PLD1 by raloxifene. Furthermore, tamoxifen
      stimulation and raloxifene inhibition of PLD activities are independent of the
      amino-terminal portion of PLD1 (amino acids 1-324). Knowledge of the mechanisms
      of action of these drugs on PLD may provide insights into the pharmacological
      action of these drugs and the role of PLD in some cancers.

PMID- 12237339
TI  - Identification of a mechanism by which the methylmercury antidotes N
      acetylcysteine and dimercaptopropanesulfonate enhance urinary metal excretion:
      transport by the renal organic anion transporter-1.
AB  - N-Acetylcysteine (NAC) and dimercaptopropanesulfonate (DMPS) are sulfhydryl
      containing compounds that produce a dramatic acceleration of urinary
      methylmercury (MeHg) excretion in poisoned animals, but the molecular mechanism
      for this effect is unknown. NAC and DMPS are themselves excreted in urine in high
      concentrations. The present study tested the hypothesis that the complexes formed
      between MeHg and these anionic chelating agents are transported from blood into
      proximal tubule cells by the basolateral membrane organic anion transporters
      (Oat) 1 and Oat3. Xenopus laevis oocytes expressing rat Oat1 showed increased
      uptake of [(14)C]MeHg when complexed with either NAC or DMPS but not when
      complexed with L-cysteine, glutathione, dimercaptosuccinate, penicillamine, or
      gamma-glutamylcysteine. In contrast, none of these MeHg complexes were
      transported by Oat3-expressing oocytes. The apparent K(m) values for Oat1
      mediated transport were 31 +/- 2 microM for MeHg-NAC and 9 +/- 2 microM for MeHg
      DMPS, indicating that these are relatively high-affinity substrates. Oat1
      mediated uptake of [(14)C]MeHg-NAC and [(14)C]MeHg-DMPS was inhibited by
      prototypical substrates for Oat1, including p-aminohippurate (PAH), and was trans
      stimulated when oocytes were preloaded with 2 mM glutarate but not glutamate.
      Conversely, efflux of [(3)H]PAH from Oat1-expressing oocytes was trans-stimulated
      by glutarate, PAH, NAC, DMPS, MeHg-NAC, MeHg-DMPS, and a mercapturic acid,
      indicating that these are transported solutes. [(3)H]PAH uptake was competitively
      inhibited by NAC (K(i) of 2.0 +/- 0.3 mM) and DMPS (K(i) of 0.10 +/- 0.02 mM),
      providing further evidence that these chelating agents are substrates for Oat1.
      These results indicate that the MeHg antidotes NAC and DMPS and their mercaptide
      complexes are transported by Oat1 but are comparatively poor substrates for Oat3.
      This is the first molecular identification of a transport mechanism by which
      these antidotes may enhance urinary excretion of toxic metals.

PMID- 12237340
TI  - Activation of the mitogen activated protein kinase extracellular signal-regulated
      kinase 1 and 2 by the nitric oxide-cGMP-cGMP-dependent protein kinase axis
      regulates the expression of matrix metalloproteinase 13 in vascular endothelial
      cells.
AB  - Matrix metalloproteinases (MMPs) are synthesized in response to diverse stimuli,
      including cytokines, growth factors, hormones, and oxidative stress. Here we show
      that the nitric oxide (NO) donor 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA
      NO) and NO from murine macrophages transcriptionally regulate MMP-13 expression
      in vascular endothelial cells (BAEC). The cGMP analog, 8-bromo-cGMP (8-Br-cGMP)
      mimicked the effect of NO, whereas incubation with the guanylate cyclase
      inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, or the cGMP-dependent
      protein kinase (PKG) inhibitor phenyl-1,N (2)- etheno-8-bromoguanosine-3',5'
      cyclic monophosphorothioate, Rp-isomer (PET) reduced the stimulatory effect of
      DEA-NO on the activation of the MMP-13 promoter. Overexpression of the catalytic
      subunit of PKG1-alpha resulted in a 5- to 6-fold increase of the MMP-13
      regulatory region over control cells. On the other hand, incubation with the
      mitogen-activated protein/extracellular signal-regulated kinase inhibitor 2'
      amino-3'-methoxyflavone (PD98059) significantly reduced DEA-NO and 8-Br-cGMP
      promoter activation and mRNA expression of MMP-13 in transfected BAEC. Moreover,
      a complex between PKG1-alpha and the G-protein Raf-1, an upstream activator of
      the extracellular signal-regulated kinase signaling pathway, was detected in
      cells overexpressing PKG1-alpha or treated either with DEA-NO or 8-Br-cGMP. Thus,
      we propose that the NO-cGMP-PKG pathway enhances MMP-13 expression by the
      activation of ERK 1,2. This effect of NO may be important in the context of
      pathophysiological conditions such as inflammation or atherogenesis [corrected].

PMID- 12237341
TI  - Revisiting an old antimicrobial drug: amphotericin B induces interleukin-1
      converting enzyme as the main factor for inducible nitric-oxide synthase
      expression in activated endothelia.
AB  - We have investigated the impact of the widely used antifungal agent Amphotericin
      B (AmB) on cytokine activated aortic endothelial cells (AEC) and their
      inflammatory response as monitored by cytokine and inducible nitric-oxide
      synthase (iNOS) expression as well as high-output nitric oxide synthesis. Because
      both blood-borne infections and systemically administered drugs will first
      encounter vessel lining endothelial cells, this cell type represents an important
      participant in innate immune reactions against xenobiotics. Culturing cytokine
      activated AEC in the presence of 1.25 microg/ml AmB, a concentration equivalent
      to serum levels during patient treatment, we find increases in iNOS promoter
      activity up to 120%, in iNOS mRNA or protein expressions by factors of up to 3.5
      +/- 1.1, and in iNOS activity of up to 180% compared with cells with cytokines
      only. In parallel, a strong increase in endothelial interleukin (IL)-1beta
      converting enzyme (ICE) and IL-1beta expression and activity was observed.
      Specific inhibition of ICE activity or IL-1beta functionality significantly
      reduces expression and activity of the iNOS to control values. Because ICE
      activity is essential for the endogenous synthesis of active IL-1beta, ICE
      overexpression represents the key signal in the AmB-induced and IL-1beta-mediated
      effects on iNOS activity. In summary, in endothelial cells, AmB strongly augments
      cytokine-induced iNOS expression and activity by increasing the expression and
      activity of the ICE. This adjuvant activity for augmented endogenous cytokine
      processing adds to the efficacy of the antimycotic activity of AmB. Furthermore,
      our data underline the relevance of the endothelial iNOS as a potent effector of
      the innate immune system.

PMID- 12237343
TI  - Sensitization by extracellular Ca(2+) of rat P2X(5) receptor and its
      pharmacological properties compared with rat P2X(1).
AB  - The recombinant rat P2X(5) (rP2X(5)) receptor, a poorly understood ATP-gated ion
      channel, was studied under voltage-clamp conditions and compared with the better
      understood homomeric rP2X(1) receptor with which it may coexist in vivo.
      Expressed in defolliculated Xenopus laevis oocytes, rP2X(5) responded to ATP with
      slowly desensitizing inward currents that, for successive responses, ran down in
      the presence of extracellular Ca(2+) (1.8 mM). Replacement of Ca(2+) with either
      Ba(2+) or Mg(2+) prevented rundown, although agonist responses were very small,
      whereas reintroduction of Ca(2+) for short periods of time (<300 s) before and
      during agonist application yielded consistently larger responses. Using this
      Ca(2+)-pulse conditioning, rP2X(5) responded to ATP and other nucleotides (ATP, 2
      methylthio-ATP, adenosine-5'-O-(thiotriphosphate), 2'-&-3'-O-(4-benzoylbenzoyl)
      ATP, alpha,beta-methylene-ATP, P(1)-P((4))-diadenosine-5'-phosphate, and more)
      with pEC(50) values within 1 log unit of respective determinations for rP2X(1).
      Only GTP was selective for rP2X(5), although 60-fold less potent than ATP. At
      rP2X(5), lowering extracellular pH reduced the potency and efficacy of ATP,
      whereas extracellular Zn(2+) ions (0.1-1000 microM) potentiated then inhibited
      ATP responses in a concentration-dependent manner. However, these modulators
      affected rP2X(1) receptors in subtly different ways-with increasing H(+) and
      Zn(2+) ion concentrations reducing agonist potency. For P2 receptor antagonists,
      the potency order at rP2X(5) was pyridoxal-5-phosphate-6-azophenyl-2',4'
      disulfonic acid (PPADS) > 2',3'-O-(2,4,6-trinitrophenyl)ATP (TNP-ATP) > suramin >
      reactive blue 2 (RB-2) > diinosine pentaphosphate (Ip(5)I). In contrast, the
      potency order at rP2X(1) was TNP-ATP = Ip(5)I > PPADS > suramin = RB-2. Thus, the
      Ca(2+)-sensitized homomeric rP2X(5) receptor is similar in agonist profile to
      homomeric rP2X(1)-although it can be distinguished from the latter by GTP
      agonism, antagonist profile, and the modulatory effects of H(+) and Zn(2+) ions.

PMID- 12237342
TI  - High affinity antagonists of the vanilloid receptor.
AB  - The vanilloid receptor VR1 has attracted great interest as a sensory transducer
      for capsaicin, protons, and heat, and as a therapeutic target. Here we
      characterize two novel VR1 antagonists, KJM429 [N-(4-tert-butylbenzyl)-N'-[4
      (methylsulfonylamino)benzyl]thiourea] and JYL1421 [N-(4-tert-butylbenzyl)-N'-[3
      fluoro-4-(methylsulfonylamino)benzyl]thiourea], with enhanced activity compared
      with capsazepine on rat VR1 expressed in Chinese hamster ovary (CHO) cells.
      JYL1421, the more potent of the two novel antagonists, inhibited
      [(3)H]resiniferatoxin binding to rVR1 with an affinity of 53.5 +/- 6.5 nM and
      antagonized capsaicin-induced calcium uptake with an EC(50) of 9.2 +/- 1.6 nM,
      reflecting 25- and 60-fold greater potencies than capsazepine. Both JYL1421 and
      KJM429 antagonized RTX as well as capsaicin and their mechanism was competitive.
      The responses to JYL1421 and KJM429 differed for calcium uptake by rVR1 induced
      by heat or pH. JYL1421 antagonized the response to both pH 6.0 and 5.5, whereas
      KJM429 antagonized at pH 6.0 but was an agonist at lower pH (<5.5). For heat,
      JYL1421 fully antagonized and KJM429 partially antagonized. Capsazepine showed
      only weak antagonism for both pH and heat. Responses of rVR1 to different
      activators could thus be differentially affected by different ligands. In
      cultured dorsal root ganglion neurons, JYL1421 and KJM429 likewise behaved as
      antagonists for capsaicin, confirming that the antagonism is not limited to
      heterologous expression systems. Finally, JYL1421 and KJM429 had little or no
      effect on ATP-induced calcium uptake in CHO cells lacking rVR1, unlike
      capsazepine. We conclude that JYL1421 is a competitive antagonist of rVR1,
      blocking response to all three of the agonists (capsaicin, heat, and protons)
      with enhanced potency relative to capsazepine.

PMID- 12237345
TI  - A Mutant S3 RNase of Petunia inflata Lacking RNase Activity Has an Allele
      Specific Dominant Negative Effect on Self-Incompatibility Interactions.
AB  - Gametophytic self-incompatibility in the Solanaceae is controlled by a
      multiallelic locus called the S locus. Growth of pollen tubes in the pistil is
      inhibited when the pollen has one of the two S alleles carried by the pistil. The
      products of a number of pistil S alleles[mdash]S proteins or S RNases[mdash]have
      been identified, and their role in controlling the pistil's ability to reject
      self-pollen has been positively established. In contrast, the existence of pollen
      S allele products has so far been inferred entirely from genetic evidence. Here,
      we introduced a modified S3 gene of Petunia inflata encoding an S3 RNase lacking
      RNase activity into P. inflata plants of the S2S3 genotype to determine whether
      the production of the mutant protein, designated S3(H93R), would have any effect
      on the ability of the transgenic plants to reject S2 and S3 pollen. Analysis of
      the self-incompatibility behavior of 49 primary transgenic plants and the progeny
      of three plants (H30, H37, and H40) that produced S3(H93R) in addition to
      producing wild-type levels of endogenous S2 and S3 RNases revealed that S3(H93R)
      had a dominant negative effect on the function of the S3 RNase in rejecting self
      pollen; however, it had no effect on the function of the S2 RNase. One likely
      explanation of the results is that S3(H93R) competes with the S3 RNase for
      binding to a common molecule, which is presumably the product of the pollen S3
      allele.

PMID- 12237344
TI  - Wounding Induces the Rapid and Transient Activation of a Specific MAP Kinase
      Pathway.
AB  - Mechanical injury in plants induces responses that are involved not only in
      healing but also in defense against a potential pathogen. To understand the
      intracellular signaling mechanism of wounding, we have investigated the
      involvement of protein kinases. Using specific antibodies, we showed that
      wounding alfalfa leaves specifically induces the transient activation of the
      p44MMK4 kinase, which belongs to the family of mitogen-activated protein kinases.
      Whereas activation of the MMK4 pathway is a post-translational process and was
      not blocked by [alpha]-amanitin and cycloheximide, inactivation depends on de
      novo transcription and translation of a protein factor(s). After wound-induced
      activation, the MMK4 pathway was subject to a refractory period of 25 min, during
      which time restimulation was not possible, indicating that the inactivation
      mechanism is only transiently active. After activation of the p44MMK4 kinase by
      wounding, transcript levels of the MMK4 gene increased, suggesting that the MMK4
      gene may be a direct target of the MMK4 pathway. In contrast, transcripts of the
      wound-inducible MsWIP gene, encoding a putative proteinase inhibitor, were
      detected only several hours after wounding. Abscisic acid, methyl jasmonic acid,
      and electrical activity are known to mediate wound signaling in plants. However,
      none of these factors was able to activate the p44MMK4 kinase in the absence of
      wounding, suggesting that the MMK4 pathway acts independently of these signals.

PMID- 12237346
TI  - Hypervariable Domains of Self-Incompatibility RNases Mediate Allele-Specific
      Pollen Recognition.
AB  - Self-incompatibility (SI) in angiosperms is a genetic mechanism that promotes
      outcrossing through rejection of self-pollen. In the Solanaceae, SI is determined
      by a multiallelic S locus whose only known product is an S RNase. S RNases show a
      characteristic pattern of five conserved and two hypervariable regions. These are
      thought to be involved in the catalytic function and in allelic specificity,
      respectively. When the Solanum chacoense S12S14 genotype is transformed with an
      S11 RNase, the styles of plants expressing significant levels of the transgene
      reject S11 pollen. A previously characterized S RNase, S13, differs from the S11
      RNase by only 10 amino acids, four of which are located in the hypervariable
      regions. When S12S14 plants were transformed with a chimeric S11 gene in which
      these four residues were substituted with those present in the S13 RNase, the
      transgenic plants acquired the S13 phenotype. This result demonstrates that the S
      RNase hypervariable regions control allelic specificity.

PMID- 12237347
TI  - Induction of Zygotic Polyembryos in Wheat: Influence of Auxin Polar Transport.
AB  - The effects of two auxin polar transport inhibitors, N-1-naphthylphthalamic acid
      (NPA) and 3,3[prime],4[prime],5,7-pentahydroxyflavone (quercetin), on attaining
      bilateral symmetry from radial symmetry during early wheat embryogenesis were
      investigated by using an in vitro culture system. Although NPA and quercetin
      belong to two different classes of auxin transport inhibitors, the phytotropins
      and the flavonoids, respectively, they induced the same specific abnormal
      phenotypes during embryo development. These abnormal embryos differentiated
      multiple meristems (i.e., multiple shoot and root meristems) and multiple organs
      (i.e., multiple coleoptiles and scutella). Multiple shoot apical meristem
      phenotypes were characterized by partly multiplied embryonic axes and
      supernumerary scutella. The differentiation of multiple primary roots in addition
      to multiple shoot meristems and multiple scutella led to the formation of
      polyembryos. The occurrence of multiple shoot meristem phenotypes depended on the
      concentration of the inhibitor and the developmental stage of the isolated
      embryo. Embryos treated with NPA or quercetin developed multiple radicle
      phenotypes less frequently than they developed multiple shoot meristem
      phenotypes. Our observations suggest that the root meristem differentiates later
      than the shoot meristem. Our data support the hypothesis that polar transport of
      auxin has a determining influence on the differentiation of the embryonic axis
      and the scutellum.

PMID- 12237348
TI  - Probing the Plant Actin Cytoskeleton during Cytokinesis and Interphase by
      Profilin Microinjection.
AB  - We have examined the cytological effects of microinjecting recombinant birch
      profilin in dividing and interphase stamen hair cells of Tradescantia virginiana.
      Microinjection of profilin at anaphase and telophase led to a marked effect on
      cytokinesis; cell plate formation was often delayed, blocked, or completely
      inhibited. In addition, the initial appearance of the cell plate was wrinkled,
      thin, and sometimes fragmented. Injection of profilin at interphase caused a
      thinning or the collapse of cytoplasmic strands and a retardation or inhibition
      of cytoplasmic streaming in a dose-dependent manner. Confocal laser scanning
      microscopy of rhodamine-phalloidin staining in vivo revealed that high levels of
      microinjected profilin induced a degradation of the actin cytoskeleton in the
      phragmoplast, the perinuclear zone, and the cytoplasmic strands. However, some
      cortical actin filaments remained intact. The data demonstrate that profilin has
      the ability to act as a regulator of actin-dependent events and that centrally
      located actin filaments are more sensitive to microinjected profilin than are
      cortical actin filaments. These results add new evidence supporting the
      hypothesis that actin filaments play a crucial role in the formation of the cell
      plate and provide mechanical support for the cytoplasmic strands in interphase
      cells.

PMID- 12237350
TI  - Slow but Steady: Reduction of Genome Size through Biased Mutation.

PMID- 12237349
TI  - Glucose and Stress Independently Regulate Source and Sink Metabolism and Defense
      Mechanisms via Signal Transduction Pathways Involving Protein Phosphorylation.
AB  - In higher plants, sugars are required not only to sustain heterotrophic growth
      but also to regulate the expression of a variety of genes. Environmental
      stresses, such as pathogen infection and wounding, activate a cascade of defense
      responses and may also affect carbohydrate metabolism. In this study, the
      relationship between sugar- and stress-activated signal transduction pathways and
      the underlying regulatory mechanism was analyzed. Photoautotrophically growing
      suspension culture cells of Chenopodium rubrum were used as a model system to
      study the effects of the metabolic regulator D-glucose and of different stress
      related stimuli on photosynthesis, sink metabolism, and defense response by
      analyzing the regulation of mRNAs for representative enzymes of these pathways.
      Glucose as well as the fungal elicitor chitosan, the phosphatase inhibitor
      endothall, and benzoic acid were shown to result in a coordinated regulatory
      mechanism. The mRNAs for phenylalanine ammonia-lyase, a key enzyme of defense
      response, and for the sink-specific extracellular invertase were induced. In
      contrast, the mRNA for the Calvin cycle enzyme ribulose bisphosphate carboxylase
      was repressed. This inverse regulatory pattern was also observed in experiments
      with wounded leaves of C. rubrum plants. The differential effect of the protein
      kinase inhibitor staurosporine on mRNA regulation demonstrates that the
      carbohydrate signal and the stress-related stimuli independently activate
      different intracellular signaling pathways that ultimately are integrated to
      coordinately regulate source and sink metabolism and activate defense responses.
      The various stimuli triggered the transient and rapid activation of protein
      kinases that phosphorylate the myelin basic protein. The involvement of
      phosphorylation in signal transduction is further supported by the effect of the
      protein kinase inhibitor staurosporine on mRNA levels.

PMID- 12237351
TI  - Reply.

PMID- 12237352
TI  - Fundamental Concepts in the Embryogenesis of Dicotyledons: A Morphological
      Interpretation of Embryo Mutants.

PMID- 12237353
TI  - Pollen Tube Growth and the Intracellular Cytosolic Calcium Gradient Oscillate in
      Phase while Extracellular Calcium Influx Is Delayed.
AB  - Ratio images of cytosolic Ca2+ (Ca2+i) in growing, fura-2-dextran-loaded Lilium
      longiflorum pollen tubes taken at 3- to 5-sec intervals showed that the tip
      focused [Ca2+]i gradient oscillates with the same period as growth. Similarly,
      measurement of the extracellular inward current, using a noninvasive ion
      selective vibrating probe, indicated that the tip-directed extracellular Ca2+
      (Ca2+o) current also oscillates with the same period as growth. Cross-correlation
      analysis revealed that whereas the [Ca2+]i gradient oscillates in phase with
      growth, the influx of Ca2+o lags by ~11 sec. Ion influx thus appears to follow
      growth, with the effect that the rate of growth at a given point determines the
      magnitude of the ion influx ~11 sec later. To explain the phase delay in the
      extracellular inward current, there must be a storage of Ca2+ for which we
      consider two possibilities: either the inward current represents the refilling of
      intracellular stores (capacitative calcium entry), or it represents the binding
      of the ion within the cell wall domain.

PMID- 12237354
TI  - Early Events Induced by the Elicitor Cryptogein in Tobacco Cells: Involvement of
      a Plasma Membrane NADPH Oxidase and Activation of Glycolysis and the Pentose
      Phosphate Pathway.
AB  - Application of the elicitor cryptogein to tobacco (cv Xanthi) is known to evoke
      external medium alkalinization, active oxygen species production, and phytoalexin
      synthesis. These are all dependent on an influx of calcium. We show here that
      cryptogein also induces calcium-dependent plasma membrane depolarization,
      chloride efflux, cytoplasm acidification, and NADPH oxidation without changes in
      NAD+ and ATP levels, indicating that the elicitor-activated redox system,
      responsible for active oxygen species production, uses NADPH in vivo. NADPH
      oxidation activates the functioning of the pentose phosphate pathway, leading to
      a decrease in glucose 6-phosphate and to the accumulation of glyceraldehyde 3
      phosphate, 3- and 2-phosphoglyceric acid, and phosphoenolpyruvate. By inhibiting
      the pentose phosphate pathway, we demonstrate that the activation of the plasma
      membrane NADPH oxidase is responsible for active oxygen species production,
      external alkalinization, and acidification of the cytoplasm. A model is proposed
      for the organization of the cryptogein responses measured to date.

PMID- 12237355
TI  - Transfer and Integration of T-DNA without Cell Injury in the Host Plant.
AB  - Agrobacterium colonizes plant cells via a gene transfer mechanism that results in
      plant tumorigenesis. Virulence (vir) genes are transcriptionally activated in the
      bacteria by plant metabolites released from the wound site. Hence, it is believed
      that agrobacteria use injuries to facilitate their entrance into the host plant
      and that the wounded state is required for plant cell competence for
      Agrobacterium-mediated gene delivery. However, our experiments using vir gene
      activated bacteria sprayed onto tobacco plantlets demonstrated that cells in
      unwounded plants could also be efficiently transformed. The condition of the
      plant cells was monitored using [beta]-glucuronidase under the control of a wound
      inducible promoter. Infection of leaf tissue is light dependent, and it is
      drastically reduced when abscisic acid is exogenously applied to the plant. Under
      these experimental conditions, stomatal opening seems to be used by Agrobacterium
      to circumvent the physical barrier of the cuticle. These results thus show that
      the proposed cellular responses evoked by wounding in higher plants are not
      essential for Agrobacterium-mediated transformation.

PMID- 12237356
TI  - Sugar Repression of a Gibberellin-Dependent Signaling Pathway in Barley Embryos.
AB  - Increasing evidence shows that sugars can act as signals affecting plant
      metabolism and development. Some of the effects of sugars on plant growth and
      development suggest an interaction of sugar signals with hormonal regulation. We
      investigated the effects of sugars on the induction of [alpha]-amylase by
      gibberellic acid in barley embryos and aleurone layers. Our results show that
      sugar and hormonal signaling interact in the regulation of gibberellic acid
      induced gene expression in barley grains. The induction of [alpha]-amylase by
      gibberellic acid in the aleurone layer is unaffected by the presence of sugars,
      but repression by carbohydrates is effective in the embryo. [alpha]-Amylase
      expression in the embryo is localized to the scutellar epithelium and is hormone
      and sugar modulated. The effects of glucose are independent from the effects of
      sugars on gibberellin biosynthesis. They are not due to an osmotic effect, they
      are independent of abscisic acid, and only hexokinase-phosphorylatable glucose
      analogs are able to trigger gene repression. Overall, the results suggest the
      existence of an interaction between the hormonal and metabolic regulation of
      [alpha]-amylase genes in barley grains.

PMID- 12237357
TI  - Soluble Signals from Cells Identified at the Cell Wall Establish a Developmental
      Pathway in Carrot.
AB  - Cells in a plant differentiate according to their positions and use cell-cell
      communication to assess these positions. Similarly, single cells in suspension
      cultures can develop into somatic embryos, and cell-cell communication is thought
      to control this process. The monoclonal antibody JIM8 labels an epitope on cells
      in specific positions in plants. JIM8 also labels certain cells in carrot
      embryogenic suspension cultures. We have used JIM8 and secondary antibodies
      coupled to paramagnetic beads to label and immunomagnetically sort single cells
      in a carrot embryogenic suspension culture into pure populations. Cells in the
      JIM8(+) population develop into somatic embryos, whereas cells in the JIM8(-)
      population do not form somatic embryos. However, certain cells in JIM8(+)
      cultures (state B cells) undergo asymmetric divisions, resulting in daughter
      cells (state C cells) that do not label with JIM8 and that sort to JIM8(-)
      cultures. State C cells are competent to form somatic embryos, and we show here
      that a conditioned growth medium from a culture of JIM8(+) cells allows state C
      cells in a JIM8(-) culture to go on and develop into somatic embryos. JIM8 labels
      cells in suspension cultures at the cell wall. Therefore, a cell with a role in
      cell-cell communication and early cell fate selection can be identified by an
      epitope in its cell wall.

PMID- 12237358
TI  - Back to the Walls.

PMID- 12237359
TI  - Assembly of Newly Imported Oxygen-Evolving Complex Subunits in Isolated
      Chloroplasts: Sites of Assembly and Mechanism of Binding.
AB  - We have examined the assembly of the nuclear-encoded subunits of the oxygen
      evolving complex (OEC) after their import into isolated intact chloroplasts. We
      showed that all three subunits examined (OE33, OE23, and OE17) partition between
      the thylakoid lumen and a site on the inner surface of the thylakoid membrane
      after import in a homologous system (e.g., pea or spinach subunits into pea or
      spinach chloroplasts, respectively). Although some interspecies protein import
      experiments resulted in OEC subunit binding, maize OE17 did not bind thylakoid
      membranes in chloroplasts isolated from peas. Newly imported OE33 and OE23 were
      washed from the membranes at the same concentrations of urea and NaCl as the
      native, indigenous proteins; this observation suggests that the former subunits
      are bound productively within the OEC. Inhibition of neither chloroplast protein
      synthesis nor light- or ATP-dependent energization of the thylakoid membrane
      significantly affected these assembly reactions, and we present evidence
      suggesting that incoming subunits actively displace those already bound to the
      thylakoid membrane. Transport of OE33 took place primarily in the stromal-exposed
      membranes and proceeded through a protease-sensitive, mature intermediate.
      Initial binding of OE33 to the thylakoid membrane occurred primarily in the
      stromal-exposed membranes, from where it migrated with measurable kinetics to the
      granal region. In contrast, OE23 assembly occurred in the granal membrane
      regions. This information is incorporated into a model of the stepwise assembly
      of oxygen-evolving photosystem II.

PMID- 12237361
TI  - Objective: The Complete Sequence of a Plant Genome.

PMID- 12237360
TI  - THE PLANT CELL'S 100th Issue: Building an Exciting Future on a Strong Foundation.

PMID- 12237362
TI  - The Promoter of the Gene Encoding the C4 Form of Phosphoenolpyruvate Carboxylase
      Directs Mesophyll-Specific Expression in Transgenic C4 Flaveria spp.
AB  - The function of the C4 mechanism of photosynthesis depends on the strict
      compartmentation of the enzymes involved. Here, we investigate the regulatory
      mechanisms that ensure the mesophyll-specific expression of the C4 isoform of
      phosphoenolpyruvate carboxylase. We show that 2 kb of the 5[prime] flanking
      region of the Flaveria trinervia C4 PpcA1 gene is sufficient to direct mesophyll
      specific expression of the [beta]-glucuronidase reporter gene in transgenic F.
      bidentis (C4) plants. In young leaves of seedlings, the activity of this promoter
      is dependent on the developmental stage of the mesophyll cells. It is induced in
      a basipetal fashion (leaf tip to base) during leaf development. The promoter
      region of the orthologous nonphotosynthetic Ppc gene of F. pringlei (C3) induces
      reporter gene expression mainly in the vascular tissue of leaves and stems as
      well as in mesophyll cells of transgenic F. bidentis plants. Our experiments
      demonstrate that during the evolution of the C4 Flaveria species, cis-acting
      elements of the C4 Ppc gene must have been altered to achieve mesophyll-specific
      expression.

PMID- 12237363
TI  - A Vacuolar-Type H+-ATPase in a Nonvacuolar Organelle Is Required for the Sorting
      of Soluble Vacuolar Protein Precursors in Tobacco Cells.
AB  - In plant cells, vacuolar matrix proteins are separated from the secretory
      proteins at the Golgi complex for transport to the vacuoles. To investigate the
      involvement of vacuolar-type ATPase (V-ATPase) in the vacuolar targeting of
      soluble proteins, we analyzed the effects of bafilomycin A1 and concanamycin A on
      the transport of vacuolar protein precursors in tobacco cells. Low concentrations
      of these inhibitors caused the missorting of several vacuolar protein precursors;
      sorting was more sensitive to concanamycin A than to bafilomycin A1. Secretion of
      soluble proteins from tobacco cells was also inhibited by bafilomycin A1 and
      concanamycin A. We next analyzed the subcellular localization of V-ATPase. V
      ATPase was found in a wide variety of endomembrane organelles. Both ATPase
      activity and ATP-dependent proton-pumping activity in the Golgi-enriched fraction
      were more sensitive to concanamycin A than to bafilomycin A1, whereas these
      activities in the tonoplast fraction were almost equally sensitive to both
      reagents. Our observations indicate that the V-ATPase in the organelle that was
      recovered in the Golgi-enriched fraction is required for the transport of
      vacuolar protein precursors and that this V-ATPase is distinguishable from the
      tonoplast-associated V-ATPase.

PMID- 12237364
TI  - Salicylic Acid Interferes with Tobacco Mosaic Virus Replication via a Novel
      Salicylhydroxamic Acid-Sensitive Mechanism.
AB  - Salicylic acid (SA) induces resistance to all plant pathogens, including
      bacteria, fungi, and viruses, but the mechanism by which SA engenders resistance
      to viruses is not known. Pretreatment of tobacco mosaic virus (TMV)-susceptible
      (nn genotype) tobacco tissue with SA reduced the levels of viral RNAs and viral
      coat protein accumulating after inoculation with TMV. Viral RNAs were not
      affected equally, suggesting that SA treatment interferes with TMV replication.
      Salicylhydroxamic acid (SHAM), an inhibitor of the mitochondrial alternative
      oxidase, antagonized both SA-induced resistance to TMV in nn genotype plants and
      SA-induced acquired resistance in resistant (NN genotype) tobacco. SHAM did not
      inhibit induction of the PR-1 pathogenesis-related protein or induction of
      resistance to Erwinia carotovora or Botrytis cinerea by SA. This indicates that
      SA induces resistance to TMV via a novel SHAM-sensitive signal transduction
      pathway (potentially involving alternative oxidase), which is distinct from that
      leading to resistance to bacteria and fungi.

PMID- 12237365
TI  - The Rate of Phaseolin Assembly Is Controlled by the Glucosylation State of Its N
      Linked Oligosaccharide Chains.
AB  - Many of the proteins that are translocated into the endoplasmic reticulum are
      glycosylated with the addition of a 14-saccharide core unit (Glc3Man9GlcNAc2) to
      specific asparagine residues of the nascent polypeptide. Glucose residues are
      then removed by endoplasmic reticulum-located glucosidases, with diglucosylated
      and monoglucosylated intermediates being formed. In this study, we used a cell
      free system constituted of wheat germ extract and bean microsomes to examine the
      role of glucose trimming in the structural maturation of phaseolin, a trimeric
      glycoprotein that accumulates in the protein storage vacuoles of bean seeds.
      Removal of glucose residues from the N-linked chains of phaseolin was blocked by
      the glucosidase inhibitors castanospermine and N-methyldeoxynojirimycin. If
      glucose trimming was not allowed to occur, the assembly of phaseolin was
      accelerated. Conversely, polypeptides bearing partially trimmed glycans were
      unable to form trimers. The effect of castanospermine on the rate of assembly was
      much more pronounced for phaseolin polypeptides that have two glycans but was
      also evident when a single glycan chain was present, indicating that glycan
      clustering can modulate the effect of glucose trimming on the rate of trimer
      formation. Therefore, the position of glycan chains and their accessibility to
      the action of glucosidases can be fundamental elements in the control of the
      structural maturation of plant glycoproteins.

PMID- 12237366
TI  - Nitrate Acts as a Signal to Induce Organic Acid Metabolism and Repress Starch
      Metabolism in Tobacco.
AB  - Nia30(145) transformants with very low nitrate reductase activity provide an in
      vivo screen to identify processes that are regulated by nitrate. Nia30(145)
      resembles nitrate-limited wild-type plants with respect to growth rate and
      protein and amino acid content but accumulates large amounts of nitrate when it
      is grown on high nitrate. The transcripts for nitrate reductase (NR), nitrite
      reductase, cytosolic glutamine synthetase, and glutamate synthase increased; NR
      and nitrite reductase activity increased in leaves and roots; and glutamine
      synthetase activity increased in roots. The transcripts for phosphoenolpyruvate
      carboxylase, cytosolic pyruvate kinase, citrate synthase, and NADP-isocitrate
      dehydrogenase increased; phosphoenolpyruvate carboxylase activity increased; and
      malate, citrate, isocitrate, and [alpha]-oxoglutarate accumulated in leaves and
      roots. There was a decrease of the ADP-glucose pyrophosphorylase transcript and
      activity, and starch decreased in the leaves and roots. After adding 12 mM
      nitrate to nitrate-limited Nia30(145), the transcripts for NR and
      phosphoenolpyruvate carboxylase increased, and the transcripts for ADP-glucose
      pyrophosphorylase decreased within 2 and 4 hr, respectively. Starch was
      remobilized at almost the same rate as in wild-type plants, even though growth
      was not stimulated in Nia30(145). It is proposed that nitrate acts as a signal to
      initiate coordinated changes in carbon and nitrogen metabolism.

PMID- 12237367
TI  - A Nuclear Mutation That Affects the 3[prime] Processing of Several mRNAs in
      Chlamydomonas Chloroplasts.
AB  - We previously created and analyzed a Chlamydomonas reinhardtii strain, [delta]26,
      in which an inverted repeat in the 3[prime] untranslated region of the
      chloroplast atpB gene was deleted. In this strain, atpB transcripts are unstable
      and heterogeneous in size, and growth is poor under conditions in which
      photosynthesis is required. Spontaneous suppressor mutations that allow rapid
      photosynthetic growth have been identified. One strain, [delta]26S, retains the
      atpB deletion yet accumulates a discrete and stable atpB transcript as a
      consequence of a recessive nuclear mutation. Unlike previously isolated
      Chlamydomonas nuclear mutations that affect chloroplast mRNA accumulation, the
      mutation in [delta]26S affects several chloroplast transcripts. For example, in
      the atpA gene cluster, the relative abundance of several messages was altered in
      a manner consistent with inefficient mRNA 3[prime] end processing. Furthermore,
      [delta]26S cells accumulated novel transcripts with 3[prime] termini in the petD
      trnR intergenic region. These transcripts are potential intermediates in 3[prime]
      end processing. In contrast, no alterations were detected for petD, atpA, or atpB
      mRNA 5[prime] ends; neither were there gross alterations detected for several
      other mRNAs, including the wild-type atpB transcript. We suggest that the gene
      identified by the suppressor mutation encodes a product involved in the
      processing of monocistronic and polycistronic messages.

PMID- 12237368
TI  - When Is a Hormone Really a Hormone?

PMID- 12237369
TI  - Reply: A Rose by Any Other Name.

PMID- 12237370
TI  - Plant Vegetative Development: From Seed and Embryo to Shoot and Root.

PMID- 12237371
TI  - Embryogenesis: A New Start in Life.

PMID- 12237372
TI  - Shoot Meristem Formation in Vegetative Development.

PMID- 12237373
TI  - Induction of Polarity in Fucoid Zygotes.

PMID- 12237374
TI  - Why Do Plant Cells Divide?

PMID- 12237375
TI  - Seed Germination and Dormancy.

PMID- 12237376
TI  - Organ Formation at the Vegetative Shoot Meristem.

PMID- 12237377
TI  - Programmed Changes in Form during Moss Development.

PMID- 12237378
TI  - Leaf Vascular Pattern Formation.

PMID- 12237379
TI  - The Phloem Sieve Element: A River Runs through It.

PMID- 12237380
TI  - Tracheary Element Differentiation.

PMID- 12237381
TI  - Programmed Cell Death in Plants.

PMID- 12237382
TI  - Signal Perception and Transduction: The Origin of the Phenotype.

PMID- 12237383
TI  - The Five "Classical" Plant Hormones.

PMID- 12237384
TI  - Coordination of Plant Metabolism and Development by the Circadian Clock.

PMID- 12237385
TI  - The Frequency and Degree of Cosuppression by Sense Chalcone Synthase Transgenes
      Are Dependent on Transgene Promoter Strength and Are Reduced by Premature
      Nonsense Codons in the Transgene Coding Sequence.
AB  - By comparing the effects of strong and weak promoters that drive sense chalcone
      synthase (Chs) transgenes in large populations of independently transformed
      plants, we show here that a strong transgene promoter is required for high
      frequency cosuppression of Chs genes and for production of the full range of
      cosuppression phenotypes. In addition, sense Chs transgenes driven by a
      cauliflower mosaic virus 35S promoter possessing a single copy of the upstream
      activator region (UAR) were found to produce a significantly lower degree of
      cosuppression than they did when the transgene promoter possessed two or four
      copies of the UAR. It has been shown elsewhere that 35S promoter strength
      increases with increasing UAR copy number. Frameshift mutations producing early
      nonsense codons in the Chs transgene were found to reduce the frequency and the
      degree of cosuppression. These results suggest that promoter strength and
      transcript stability determine the degree of cosuppression, supporting the
      hypothesis that sense cosuppression is a response to the accumulation of
      transcripts at high concentrations. This conclusion was shown to apply to single
      copy transgenes but not necessarily to inversely repeated transgenes. The results
      presented here also have significance for efficient engineering of cosuppression
      phenotypes for use in research and agriculture.

PMID- 12237386
TI  - Chlamydomonas Xanthophyll Cycle Mutants Identified by Video Imaging of
      Chlorophyll Fluorescence Quenching.
AB  - The photosynthetic apparatus in plants is protected against oxidative damage by
      processes that dissipate excess absorbed light energy as heat within the light
      harvesting complexes. This dissipation of excitation energy is measured as
      nonphotochemical quenching of chlorophyll fluorescence. Nonphotochemical
      quenching depends primarily on the [delta]pH that is generated by photosynthetic
      electron transport, and it is also correlated with the amounts of zeaxanthin and
      antheraxanthin that are formed from violaxanthin by the operation of the
      xanthophyll cycle. To perform a genetic dissection of nonphotochemical quenching,
      we have isolated npq mutants of Chlamydomonas by using a digital video-imaging
      system. In excessive light, the npq1 mutant is unable to convert violaxanthin to
      antheraxanthin and zeaxanthin; this reaction is catalyzed by violaxanthin de
      epoxidase. The npq2 mutant appears to be defective in zeaxanthin epoxidase
      activity, because it accumulates zeaxanthin and completely lacks antheraxanthin
      and violaxanthin under all light conditions. Characterization of these mutants
      demonstrates that a component of nonphotochemical quenching that develops in vivo
      in Chlamydomonas depends on the accumulation of zeaxanthin and antheraxanthin via
      the xanthophyll cycle. However, observation of substantial, rapid, [delta]pH
      dependent nonphotochemical quenching in the npq1 mutant demonstrates that the
      formation of zeaxanthin and antheraxanthin via violaxanthin de-epoxidase activity
      is not required for all [delta]pH-dependent nonphotochemical quenching in this
      alga. Furthermore, the xanthophyll cycle is not required for survival of
      Chlamydomonas in excessive light.

PMID- 12237387
TI  - Phloem Unloading in Sink Leaves of Nicotiana benthamiana: Comparison of a
      Fluorescent Solute with a Fluorescent Virus.
AB  - Using noninvasive imaging techniques, we compared phloem unloading of the
      membrane-impermeant, fluorescent solute carboxyfluorescein (CF) with that of
      potato virus X expressing the gene for the green fluorescent protein. Although
      systemic virus transport took considerably longer to occur than did CF transport,
      unloading of both solute and virus occurred predominantly from the class III vein
      network, a highly branched veinal system found between class II veins. The minor
      veins (classes IV and V) played no role in solute or virus import but were shown
      to be functional in xylem transport at the time of import by labeling with Texas
      Red dextran. After virus exit from the class III phloem, the minor veins
      eventually became infected by cell-to-cell virus movement from the mesophyll.
      During the sink/source transition, phloem unloading of CF was inhibited from
      class III veins before the cessation of phloem import through them, suggesting a
      symplastic isolation of the phloem in class III veins before its involvement in
      export. The progression of the sink/source transition for carbon was unaffected
      by the presence of the virus in the sink leaf. However, the virus was unable to
      cross the sink/source boundary for carbon that was present at the time of viral
      entry, suggesting a limited capacity for cell-to-cell virus movement into the
      apical (source) region of the leaf. A functional model of the sink/source
      transition in Nicotiana benthamiana is presented. This model provides a framework
      for the analysis of solute and virus movement in leaves.

PMID- 12237388
TI  - Interaction Analyses of Genes Required for Resistance Responses to Powdery Mildew
      in Barley Reveal Distinct Pathways Leading to Leaf Cell Death.
AB  - Race-specific resistance in barley to the powdery mildew fungus (Erysiphe
      graminis f sp hordei) is associated with a cell death reaction (hypersensitive
      response [HR]). Genetically, it is dependent on dominant resistance genes (Mlx),
      and in most cases, it is also dependent on Rar1 and Rar2. Non-race-specific
      resistance to the fungus, which is due to the lack of the Mlo wild-type allele,
      is dependent on Ror1 and Ror2 and is not associated with an HR in the region of
      pathogen attack. However, the absence of the Mlo wild-type allele stimulates a
      spontaneous cell death response in foliar tissue. This response is also
      controlled by Ror1 and Ror2, as indicated by trypan blue staining patterns. Lack
      of Mlo enhances transcript accumulation of pathogenesis-related genes upon fungal
      challenge, and this response is diminished by mutations in Ror genes. Using DNA
      marker-assisted selection of genotypes, we provide evidence, via gene interaction
      studies, that Ror1 and Ror2 are not essential components of race-specific
      resistance and do not compromise hypersensitive cell death. Reciprocal
      experiments show that neither is Rar1 a component of mlo-controlled resistance
      nor does it affect spontaneous cell death. We show that mlo- and Ror-dependent
      resistance is active when challenged with E. g. f sp tritici, a nonhost pathogen
      of barley. Our observations suggest separate genetic pathways operating in race
      specific and non-race-specific resistance; they indicate also a separate genetic
      control of hypersensitive and spontaneous cell death in foliar tissue.

PMID- 12237389
TI  - Characterization of Post-Transcriptionally Suppressed Transgene Expression That
      Confers Resistance to Tobacco Etch Virus Infection in Tobacco.
AB  - Tobacco lines expressing transgenes that encode tobacco etch virus (TEV) coat
      protein (CP) mRNA with or without nonsense codons give rise to TEV-resistant
      tissues that have reduced levels of TEV CP mRNA while maintaining high levels of
      transgene transcriptional activity. Two phenotypes for virus resistance in the
      lines containing the transgene have been described: immune (no virus infection)
      and recovery (initial systemic symptoms followed by gradual recovery over several
      weeks). Here, we show that at early times in development, immune lines are
      susceptible to TEV infection and accumulate full-length CP mRNA. Therefore,
      immune lines also exhibit meiotic resetting, as is seen in the recovery lines,
      providing molecular evidence for a common mechanism of gene silencing and virus
      resistance in both cases. We also investigated the characteristics of two sets of
      low molecular weight RNAs that appear only in silenced tissue. One set has nearly
      intact 5[prime] ends, lacks poly(A) tails, and is associated with polyribosomes;
      the second set contains the 3[prime] end of the mRNA. Treating silenced leaf
      tissue with cycloheximide resulted in decreased levels of full-length mRNA and an
      increase in the levels of the low molecular weight RNAs, supporting a cytoplasmic
      decay mechanism that does not require ongoing translation. Surprisingly, mRNA
      from the transgene containing nonsense codons was associated with more ribosomes
      than expected, possibly resulting from translation from a start codon downstream
      of the introduced translational stop codons. We present a hypothesis for
      transgene/viral RNA degradation in which RNA degradation occurs in the cytoplasm
      while in association with polyribosomes.

PMID- 12237390
TI  - Specific Binding of the Syringolide Elicitors to a Soluble Protein Fraction from
      Soybean Leaves.
AB  - Syringolides are glycolipid elicitors produced by Gram-negative bacteria
      expressing Pseudomonas syringae avirulence gene D. The syringolides mediate gene
      for-gene complementarity, inducing the hypersensitive response only in soybean
      plants carrying the Rpg4 disease resistance gene. A site(s) for 125I-syringolide
      1 was detected in the soluble protein fraction from soybean leaves, but no
      evidence for ligand-specific binding to the microsomal fraction was obtained. The
      Kd value for syringolide 1 binding with the soluble fraction was 8.7 nM, and
      binding was greatly reduced by prior protease treatment or heating. A native gel
      assay was also used to demonstrate ligand-specific binding of labeled syringolide
      1 with a soluble protein(s). Competition studies with 125I-syringolide 1 and
      several structural derivatives demonstrated a direct correlation between binding
      affinity to the soluble fraction and elicitor activity. However, differential
      competition binding studies disclosed no differences in syringolide binding to
      soluble fractions from Rpg4/Rpg4 or rpg4/rpg4 soybean leaves. Thus, the observed
      binding site fulfills several criteria expected of an intracellular receptor for
      the syringolides, but it is most likely not encoded by the Rpg4 gene. Instead,
      the Rpg4 gene product may function subsequent to elicitor binding, possibly in
      intracellular signal transduction.

PMID- 12237391
TI  - Actin Purified from Maize Pollen Functions in Living Plant Cells.
AB  - A vast array of actin binding proteins (ABPs), together with intracellular
      signaling molecules, modulates the spatiotemporal distribution of actin filaments
      in eukaryotic cells. To investigate the complex regulation of actin organization
      in plant cells, we designed experiments to reconstitute actin-ABP interactions in
      vitro with purified components. Because vertebrate skeletal [alpha]-actin has
      distinct and unpredictable binding affinity for nonvertebrate ABPs, it is
      essential that these in vitro studies be performed with purified plant actin.
      Here, we report the development of a new method for isolating functional actin
      from maize pollen. The addition of large amounts of recombinant profilin to
      pollen extracts facilitated the depolymerization of actin filaments and the
      formation of a profilin-actin complex. The profilin-actin complex was then
      isolated by affinity chromatography on poly-L-proline-Sepharose, and actin was
      selectively eluted with a salt wash. Pollen actin was further purified by one
      cycle of polymerization and depolymerization. The recovery of functional actin by
      this rapid and convenient procedure was substantial; the average yield was 6 mg
      of actin from 10 g of pollen. We undertook an initial physicochemical
      characterization of this native pollen actin. Under physiological conditions,
      pollen actin polymerized with kinetics similar in quality to those for vertebrate
      [alpha]-actin and had a critical concentration for assembly of 0.6 [mu]M.
      Moreover, pollen actin interacted specifically and in a characteristic fashion
      with several ABPs. Tradescantia cells were microinjected and used as an
      experimental system to study the behavior of pollen actin in vivo. We
      demonstrated that purified pollen actin ameliorated the effects of injecting
      excess profilin into live stamen hair cells.

PMID- 12237392
TI  - A Transcriptionally Active State Is Required for Post-Transcriptional Silencing
      (Cosuppression) of Nitrate Reductase Host Genes and Transgenes.
AB  - Using tobacco nitrate reductase cosuppression as a model system of post
      transcriptional gene silencing, we analyzed the influence of DNA and RNA dosages
      both together and independently. For this purpose, zero, one, two, or four active
      or transcriptionally silenced copies of a cauliflower mosaic virus 35S-Nia2
      transgene were combined by transformation and subsequent crosses with zero, one,
      two, three, or four active, disrupted, or transcriptionally repressed copies of
      the wild-type host Nia genes. The analysis of the corresponding transgenic lines
      revealed that (1) the percentage of isogenic plants that are affected by
      cosuppression depends directly upon the relative dosage of both host gene and
      transgene; (2) transcriptional silencing of the 35S-Nia transgene impedes
      cosuppression; and (3) the absence of host gene transcription reduces the
      frequency of cosuppression or delays its triggering. Taken together, these
      results indicate that transgene DNA per se is not sufficient to trigger post
      transcriptional cosuppression of nitrate reductase host genes and transgenes. The
      requirement for a transcriptionally active state is discussed with respect to
      both the RNA dosage and the DNA-DNA pairing hypotheses.

PMID- 12237393
TI  - Do Plants Have a One-Way Ticket to Genomic Obesity?

PMID- 12237394
TI  - Expression of the C4 Me1 Gene from Flaveria bidentis Requires an Interaction
      between 5[prime] and 3[prime] Sequences.
AB  - The efficient functioning of C4 photosynthesis requires the strict
      compartmentation of a suite of enzymes in either mesophyll or bundle sheath
      cells. To determine the mechanism controlling bundle sheath cell-specific
      expression of the NADP-malic enzyme, we made a set of chimeric constructs using
      the 5[prime] and 3[prime] regions of the Flaveria bidentis Me1 gene fused to the
      [beta]-glucuronidase gusA reporter gene. The pattern of GUS activity in stably
      transformed F. bidentis plants was analyzed by histochemical and cell separation
      techniques. We conclude that the 5[prime] region of Me1 determines bundle sheath
      specificity, whereas the 3[prime] region contains an apparent enhancer-like
      element that confers high-level expression in leaves. The interaction of 5[prime]
      and 3[prime] sequences was dependent on factors that are present in the C4 plant
      but not found in tobacco.

PMID- 12237395
TI  - Light-Dependent Spatial and Temporal Expression of Pigment Regulatory Genes in
      Developing Maize Seeds.
AB  - Both light and developmental stimuli are directly involved in the regulation of
      plant gene expression. In maize, activation of the anthocyanin pathway represents
      an excellent model system for studying the interactions between an external
      factor, such as light, and internal factors that regulate plant and seed
      development. By analyzing in detail the aleurone and pericarp seed layers,
      different developmental windows for light have been found in the two
      tissues[mdash]the former in the advanced stages of development and the latter in
      the early stages of seed development. Transcriptional control of the structural
      genes involved in anthocyanin deposition within the pericarp is known to be
      exerted by the Sn and pl genes, whereas the aleurone is controlled by the R and
      C1 regulatory genes. By using in situ hybridization analysis, we detected tissue
      specific expression of Sn and R in the seed layers, revealing a correlation
      between structural gene activation and anthocyanin accumulation. In addition, RNA
      gel blot analysis revealed that Sn expression is enhanced by light, whereas the R
      gene expression is not. However, the light-induced expression of the myb-type
      genes C1 and pl, detected by reverse transcriptase-polymerase chain reaction, was
      found to be the limiting factor for conferring the developmental competence of
      the pericarp and the aleurone layers to light responsiveness.

PMID- 12237396
TI  - Two Distinct Sources of Elicited Reactive Oxygen Species in Tobacco Epidermal
      Cells.
AB  - Reactive oxygen species (ROS) play a prominent role in early and later stages of
      the plant pathogenesis response, putatively acting as both cellular signaling
      molecules and direct antipathogen agents. A single-cell assay, based on the
      fluorescent probe dichlorofluorescein, was used to scrutinize the generation and
      movement of ROS in tobacco epidermal tissue. ROS, generated within cells, quickly
      moved apoplastically as H2O2 into neighboring cells. Two classes of rapidly
      elicited intracellular ROS, originating from distinct sources, were
      distinguished. Cryptogein, the fungal elicitor from Phytophthora cryptogea,
      induced ROS from a flavin-containing oxidase source. ROS accumulation could be
      inhibited by a number of pharmacological agents, suggesting induction through an
      active signal transduction pathway. The insensitivity of the increase in ROS to
      the external addition of enzymes that dissipate ROS suggests that this oxidative
      increase is primarily intracellular. In contrast, amines and polyamines,
      compounds that form during wounding and pathogenesis, induced ROS at an
      apoplastic site from peroxidase- or amine oxidase-type enzyme(s). Salicylic acid,
      a putative inhibitor of cellular catalases and peroxidases, did not induce
      cellular ROS, as measured by dichlorofluorescein fluorescence. The physiological
      relevance of ROS-generated signals was indicated by the rapid alteration of the
      epidermal cell glutathione pool and the cellular redox state. In addition,
      induction of ROS by all elicitors was correlated with subsequent cell death.

PMID- 12237397
TI  - Inhibition of Pollen Tube Elongation by Microinjected Anti-Rop1Ps Antibodies
      Suggests a Crucial Role for Rho-Type GTPases in the Control of Tip Growth.
AB  - Microinjection of anti-Rop1Ps antibodies was used to assess the function of a tip
      localized Rho-type GTPase, Rop, in controlling pollen tube growth. Injected
      antibodies induced sustained growth arrest within 1 to 2 min after injection but
      did not affect cytoplasmic streaming. Coinjection with Rop rescued antibody
      induced growth inhibition, indicating that injected antibodies specifically block
      the activity of Rop GTPases. Antibody-induced inhibition was significantly
      enhanced in the presence of a lower threshold of extracellular [Ca2+] or a
      subinhibitory dosage of caffeine. In contrast, injection of the C3 toxin, which
      inactivates a different Rho-type GTPase, arrested tube elongation 10 to 20 min
      after injection. C3-induced growth arrest was accompanied by the cessation of
      cytoplasmic streaming. These data suggest that Rho-type GTPases play a pivotal
      role in the control of pollen tube elongation. We propose that Rop may regulate a
      Ca2+-dependent pathway involved in vesicle docking/fusion, whereas a C3-sensitive
      Rho GTPase may mediate cytoplasmic streaming.

PMID- 12237398
TI  - Mechanism of ABC transporters: a molecular dynamics simulation of a well
      characterized nucleotide-binding subunit.
AB  - ATP-binding cassette (ABC) transporters are membrane-bound molecular pumps that
      form one of the largest of all protein families. Several of them are central to
      phenomena of biomedical interest, including cystic fibrosis and resistance to
      chemotherapeutic drugs. ABC transporters share a common architecture comprising
      two hydrophilic nucleotide-binding domains (NBDs) and two hydrophobic
      transmembrane domains (TMDs) that form the substrate pathway across the membrane.
      The conformational changes in the NBDs induced by ATP hydrolysis and the means by
      which they are transmitted to the TMDs to effect substrate translocation remain
      largely unknown. We have performed a molecular dynamics simulation of HisP, the
      well studied NBD of the bacterial histidine permease, to identify hinges and
      switches of the NBD conformational transitions and subunit-subunit interfaces.
      This analysis reveals that the TMDs regulate ATP hydrolysis by controlling
      conformational transitions of the NBD helical domains, and identifies the
      conformational changes and the crucial TMD:NBD interface, by which the energy of
      ATP hydrolysis is transmitted to the TMDs. We also define the conformational
      transitions of the Q-loop, a key element of the NBD mechanism, and identify
      pathways by which Q-loop switching is coordinated with TMD and NBD conformational
      changes. We propose a model for the catalytic cycle of ABC transporters that
      shows how substrate-binding and transport by the TMDs may be coordinated and
      coupled with ATP binding and hydrolysis in the NBDs.

PMID- 12237399
TI  - Evolution of moth sex pheromones via ancestral genes.
AB  - Mate finding in most moth species involves long-distance signaling via female
      emitted sex pheromones. There is a great diversity of pheromone structures used
      throughout the Lepidoptera, even among closely related species. The conundrum is
      how signal divergence has occurred. With strong normalizing selection pressure on
      blend composition and response preferences, it is improbable that shifts to
      pheromones of diverse structures occur through adaptive changes in small steps.
      Here, we present data supporting the hypothesis that a major shift in the
      pheromone of an Ostrinia species occurred by activation of a nonfunctional
      desaturase gene transcript present in the pheromone gland. We also demonstrate
      the existence of rare males that respond to the new pheromone blend. Their
      presence would allow for asymmetric tracking of male response to the new blend
      and, thus, evolution of an Ostrinia species with structurally different sex
      pheromone components.

PMID- 12237400
TI  - Intrinsic and extrinsic contributions to stochasticity in gene expression.
AB  - Gene expression is a stochastic, or "noisy," process. This noise comes about in
      two ways. The inherent stochasticity of biochemical processes such as
      transcription and translation generates "intrinsic" noise. In addition,
      fluctuations in the amounts or states of other cellular components lead
      indirectly to variation in the expression of a particular gene and thus represent
      "extrinsic" noise. Here, we show how the total variation in the level of
      expression of a given gene can be decomposed into its intrinsic and extrinsic
      components. We demonstrate theoretically that simultaneous measurement of two
      identical genes per cell enables discrimination of these two types of noise.
      Analytic expressions for intrinsic noise are given for a model that involves all
      the major steps in transcription and translation. These expressions give the
      sensitivity to various parameters, quantify the deviation from Poisson
      statistics, and provide a way of fitting experiment. Transcription dominates the
      intrinsic noise when the average number of proteins made per mRNA transcript is
      greater than approximately 2. Below this number, translational effects also
      become important. Gene replication and cell division, included in the model,
      cause protein numbers to tend to a limit cycle. We calculate a general form for
      the extrinsic noise and illustrate it with the particular case of a single
      fluctuating extrinsic variable-a repressor protein, which acts on the gene of
      interest. All results are confirmed by stochastic simulation using plausible
      parameters for Escherichia coli.

PMID- 12237401
TI  - Range image statistics can explain the anomalous perception of length.
AB  - A long-standing puzzle in visual perception is that the apparent extent of a
      spatial interval (e.g., the distance between two points or the length of a line)
      does not simply accord with the length of the stimulus but varies as a function
      of orientation in the retinal image. Here, we show that this anomaly can be
      explained by the statistical relationship between the length of retinal
      projections and the length of their real-world sources. Using a laser range
      scanner, we acquired a database of natural images that included the three
      dimensional location of every point in the scenes. An analysis of these range
      images showed that the average length of a physical interval in three-dimensional
      space changes systematically as a function of the orientation of the
      corresponding interval in the projected image, the variation being in good
      agreement with perceived length. This evidence implies that the perception of
      visual space is determined by the probability distribution of the possible real
      world sources of retinal images.

PMID- 12237402
TI  - Adenoviral gene transfer of endothelial nitric-oxide synthase (eNOS) partially
      restores normal pulmonary arterial pressure in eNOS-deficient mice.
AB  - It has been shown that mice deficient in the gene coding for endothelial nitric
      oxide synthase (eNOS) have increased pulmonary arterial pressure and pulmonary
      vascular resistance. In the present study, the effect of transfer to the lung of
      an adenoviral vector encoding the eNOS gene (AdCMVeNOS) on pulmonary arterial
      pressure and pulmonary vascular resistance was investigated in eNOS-deficient
      mice. One day after intratracheal administration of AdCMVeNOS to eNOS(-/-) mice,
      there was an increase in eNOS protein, cGMP levels, and calcium-dependent
      conversion of l-arginine to l-citrulline in the lung. The increase in eNOS
      protein and activity in eNOS(-/-) mice was associated with a reduction in mean
      pulmonary arterial pressure and pulmonary vascular resistance when compared with
      values in eNOS-deficient mice treated with vehicle or a control adenoviral vector
      coding for beta-galactosidase, AdCMVbetagal. These data suggest that in vivo gene
      transfer of eNOS to the lung in eNOS(-/-) mice can increase eNOS staining, eNOS
      protein, calcium-dependent NOS activity, and cGMP levels and partially restore
      pulmonary arterial pressure and pulmonary vascular resistance to near levels
      measured in eNOS(+/+) mice. Thus, the major finding in this study is that in vivo
      gene transfer of eNOS to the lung in large part corrects a genetic deficiency
      resulting from eNOS deletion and may be a useful therapeutic intervention for the
      treatment of pulmonary hypertensive disorders in which eNOS activity is reduced.

PMID- 12237403
TI  - Life history consequences of mammal sibling rivalry.
AB  - Mammal life history traits relating to growth and reproduction are extremely
      diverse. Sibling rivalry may contribute to selection pressures influencing this
      diversity, because individuals that are relatively large at birth typically have
      an advantage in competition for milk. However, selection for increased growth
      rate is likely to be constrained by kin selection and physiological costs. Here,
      we present and test a model examining the ESS (evolutionarily stable strategy)
      balance between these constraints and advantages associated with increased
      prenatal growth in mammal sibling rivalry. Predictions of the model are supported
      by results of comparative analyses for the Carnivora and Insectivora, which
      demonstrate an increase in prenatal growth rate with increasing intensity of
      postnatal scramble competition, and a decrease in postnatal growth rate relative
      to size at birth. Because increased prenatal growth rates are predicted to select
      for reduced gestation length under certain conditions, our study also indicates
      that sibling rivalry may contribute to selection pressures influencing variation
      in altriciality and precociality among mammals.

PMID- 12237404
TI  - Size-dependent life-history traits promote catastrophic collapses of top
      predators.
AB  - Catastrophic population collapses such as observed in many exploited fish
      populations have been argued to result from depensatory growth mechanisms (i.e.,
      reduced reproductive success at low population densities, also known as Allee
      effect). Empirical support for depensation from population-level data is,
      however, hard to obtain and inconclusive. Using a size-structured, individual
      based model we show that catastrophic population collapses may nonetheless be an
      intrinsic property of many communities, because of two general aspects of
      individual life history: size- and food-dependent individual growth and
      individual mortality decreasing with body size. Positive density dependence,
      characteristic for depensatory growth mechanisms and catastrophic behavior,
      results as a direct and robust consequence of the interplay between these
      individual life-history traits, which are commonly found in many species.

PMID- 12237405
TI  - The heterotrimeric G protein alpha subunit acts upstream of the small GTPase Rac
      in disease resistance of rice.
AB  - We used rice dwarf1 (d1) mutants lacking a single-copy Galpha gene and addressed
      Galpha's role in disease resistance. d1 mutants exhibited a highly reduced
      hypersensitive response to infection by an avirulent race of rice blast.
      Activation of PR gene expression in the leaves of the mutants infected with rice
      blast was delayed for 24 h relative to the wild type. H(2)O(2) production and PR
      gene expression induced by sphingolipid elicitors (SE) were strongly suppressed
      in d1 cell cultures. Expression of the constitutively active OsRac1, a small
      GTPase Rac of rice, in d1 mutants restored SE-dependent defense signaling and
      resistance to rice blast. Galpha mRNA was induced by an avirulent race of rice
      blast and SE application on the leaf. These results indicated the role of Galpha
      in R gene-mediated disease resistance of rice. We have proposed a model for the
      defense signaling of rice in which the heterotrimeric G protein functions
      upstream of the small GTPase OsRac1 in the early steps of signaling.

PMID- 12237406
TI  - Expression of functional neurotransmitter receptors in Xenopus oocytes after
      injection of human brain membranes.
AB  - The Xenopus oocyte is a very powerful tool for studies of the structure and
      function of membrane proteins, e.g., messenger RNA extracted from the brain and
      injected into oocytes leads to the synthesis and membrane incorporation of many
      types of functional receptors and ion channels, and membrane vesicles from
      Torpedo electroplaques injected into oocytes fuse with the oocyte membrane and
      cause the appearance of functional Torpedo acetylcholine receptors and Cl(-)
      channels. This approach was developed further to transplant already assembled
      neurotransmitter receptors from human brain cells to the plasma membrane of
      Xenopus oocytes. Membranes isolated from the temporal neocortex of a patient,
      operated for intractable epilepsy, were injected into oocytes and, within a few
      hours, the oocyte membrane acquired functional neurotransmitter receptors to
      gamma-aminobutyric acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid, kainate, and glycine. These receptors were also expressed in the plasma
      membrane of oocytes injected with mRNA extracted from the temporal neocortex of
      the same patient. All of this makes the Xenopus oocyte a more useful model than
      it already is for studies of the structure and function of many human membrane
      proteins and opens the way to novel pathophysiological investigations of some
      human brain disorders.

PMID- 12237407
TI  - Gradients of substrate-bound laminin orient axonal specification of neurons.
AB  - Little is known about the influence of substrate-bound gradients on neuronal
      development, since it has been difficult to fabricate gradients over the
      distances typically required for biological studies (a few hundred micrometers).
      This article demonstrates a generally applicable technique for the fabrication of
      substrate-bound gradients of proteins with complex shapes, using laminar flows in
      microchannels. Gradients that range from pure laminin to pure BSA were formed in
      solution by using a network of microchannels, and these proteins were allowed to
      adsorb onto a homogeneous layer of poly-l-lysine. Rat hippocampal neurons were
      cultivated on these substrate-bound gradients. Analysis of optical images of
      these neurons showed that axon specification is oriented in the direction of
      increasing surface density of laminin. Linear gradients in laminin adsorbed from
      a gradient in solution having a slope of nabla [laminin] > about 0.06 microg
      (ml.microm)(-1) (defined by dividing the change of concentration of laminin in
      solution over the distance of the gradient) orient axon specification, whereas
      those with nabla [laminin] < about 0.06 microg (ml.microm)(-1) have no effect.

PMID- 12237408
TI  - Growth suppression of human carcinoma cells by reintroduction of the p300
      coactivator.
AB  - The p300 and closely related cAMP response element binding protein (CREB)-binding
      protein (CBP) acetyltransferases function as global transcriptional coactivators
      and play important roles in a broad spectrum of biological processes, including
      cell proliferation and differentiation. A role of p300/CBP in tumor suppression
      has been proposed from the fact that these coactivators are targeted by viral
      oncoproteins and that biallelic mutations of p300 have been identified in
      carcinomas. Here, we show that transcriptional response to the transforming
      growth factor beta (TGF-beta), an inhibitor of epithelial cell growth, was
      severely impaired in human carcinoma cell lines carrying p300 mutations
      accompanied by inactivation of the second allele, and that wild-type expression
      restored TGF-beta-dependent transcriptional activity. Furthermore, reintroduction
      of wild-type p300 suppressed the growth of p300-deficient carcinoma cells,
      whereas p300 did not inhibit the growth of carcinoma cells examined, which have
      no detectable alterations in p300 protein and retain the TGF-beta-dependent
      transcriptional response. In addition, tumor-derived mutants missing the
      bromodomain or glutamine-rich region, which are respectively important for
      chromatin interaction and coactivator activities, lost the suppressive activity.
      In contrast, CBP exhibited no or reduced ability to suppress the growth of p300
      deficient carcinoma cells. These results provide experimental evidence to show
      that p300 acts as a suppressor of tumor cell growth and suggest a distinct role
      of p300 in suppression of epithelial tumors.

PMID- 12237410
TI  - Timing-dependent limbic-motor synaptic integration in the nucleus accumbens.
AB  - The nucleus accumbens is a brain region in which limbic and motor inputs
      converge. How these information modalities shape accumbens output is not clearly
      understood. Here, we report that synaptic inputs from the prefrontal cortex and
      limbic structures interact differently depending on their timing. Coincident
      inputs may result in enhancing information flow through the nucleus accumbens.
      Responses to asynchronous inputs are affected by their relative order of arrival,
      with limbic inputs allowing subsequent prefrontal responses, and prefrontal
      inputs dampening limbic responses. These mechanisms allow for both coincidence
      detection and input selection in this integrative brain region.

PMID- 12237409
TI  - Direct stimulation of transcription by negative cofactor 2 (NC2) through TATA
      binding protein (TBP).
AB  - Negative cofactor 2 (NC2) is an evolutionarily conserved transcriptional
      regulator that was originally identified as an inhibitor of basal transcription.
      Its inhibitory mechanism has been extensively characterized; NC2 binds to the
      TATA-binding protein (TBP), blocking the recruitment of TFIIA and TFIIB, and
      thereby inhibiting preinitiation complex assembly. NC2 is also required for
      expression of many yeast genes in vivo and stimulates TATA-less transcription in
      a Drosophila in vitro transcription system, but the mechanism responsible for the
      NC2-mediated stimulation of transcription is not understood. Here we establish
      that yeast NC2 can directly stimulate activated transcription from TATA-driven
      promoters both in vivo and in vitro, and moreover that this positive role
      requires the same surface of TBP that mediates the NC2 repression activity. On
      the basis of these results, we propose a model to explain how NC2 can mediate
      both repression and activation through the same surface of TBP.

PMID- 12237411
TI  - Quantitative imaging of cis-regulatory reporters in living embryos.
AB  - A confocal laser scanning microscopy method has been developed for the
      quantitation of green fluorescent protein (GFP) as a reporter of gene activity in
      living three-dimensional structures such as sea urchin and starfish embryos. This
      method is between 2 and 50 times more accurate than conventional confocal
      microscopy procedures depending on the localization of GFP within an embryo. By
      using coinjected Texas red dextran as an internal fluorescent standard, the
      observed GFP intensity is corrected for variations in laser excitation and
      fluorescence collection efficiency. To relate the recorded image intensity to the
      number of GFP molecules, the embryos were lysed gently, and a fluorometric
      analysis of their contents was performed. Confocal laser scanning microscopy data
      collection from a single sea urchin blastula required less than 2 min, thereby
      allowing gene expression in dozens of embryos to be monitored in parallel with
      high spatial and temporal resolution.

PMID- 12237412
TI  - Molecular basis for the explanation of the exponential growth of polyelectrolyte
      multilayers.
AB  - The structure of poly(l-lysine) (PLL)/hyaluronan (HA) polyelectrolyte multilayers
      formed by electrostatic self-assembly is studied by using confocal laser scanning
      microscopy, quartz crystal microbalance, and optical waveguide lightmode
      spectroscopy. These films exhibit an exponential growth regime where the
      thickness increases exponentially with the number of deposited layers, leading to
      micrometer thick films. Previously such a growth regime was suggested to result
      from an "in" and "out" diffusion of the PLL chains through the film during
      buildup, but direct evidence was lacking. The use of dye-conjugated
      polyelectrolytes now allows a direct three-dimensional visualization of the film
      construction by introducing fluorescent polyelectrolytes at different steps
      during the film buildup. We find that, as postulated, PLL diffuses throughout the
      film down into the substrate after each new PLL injection and out of the film
      after each PLL rinsing and further after each HA injection. As PLL reaches the
      outer layer of the film it interacts with the incoming HA, forming the new HA/PLL
      layer. The thickness of this new layer is thus proportional to the amount of PLL
      that diffuses out of the film during the buildup step, which explains the
      exponential growth regime. HA layers are also visualized but no diffusion is
      observed, leading to a stratified film structure. We believe that such a
      diffusion-based buildup mechanism explains most of the exponential-like growth
      processes of polyelectrolyte multilayers reported in the literature.

PMID- 12237413
TI  - A signal transduction protein cues proteolytic events critical to Caulobacter
      cell cycle progression.
AB  - Temporally controlled proteolysis of the essential response regulator, CtrA, is
      critical for cell cycle progression in Caulobacter crescentus. CtrA binds to and
      silences the origin of replication in swarmer cells. The initiation of
      replication depends on the proteolysis of CtrA. We present evidence that DivK, an
      essential single-domain response regulator, contributes to the control of the
      G(1)-S transition by signaling the temporally controlled proteolysis of CtrA. In
      a divK-cs mutant at the restrictive temperature, the initiation of DNA
      replication is blocked because of the retention of CtrA. A shift of cells from
      restrictive to permissive temperature results in rapid degradation of CtrA,
      initiation of DNA replication, and the resumption of cell cycle progression,
      including the ordered expression of genes involved in chromosome replication and
      polar organelle biogenesis. CtrA binds to and regulates the promoters of two
      genes critical to its temporally controlled proteolysis, divK and clpP, providing
      a transcriptional feedback loop for the control of cell cycle progression.

PMID- 12237414
TI  - Roles of uracil-DNA glycosylase and dUTPase in virus replication.
AB  - Herpesviruses and poxviruses are known to encode the DNA repair enzyme uracil-DNA
      glycosylase (UNG), an enzyme involved in the base excision repair pathway that
      specifically removes the RNA base uracil from DNA, while at least one retrovirus
      (human immunodeficiency virus type 1) packages cellular UNG into virus particles.
      In these instances, UNG is implicated as being important in virus replication.
      However, a clear understanding of the role(s) of UNG in virus replication remains
      elusive. Herpesviruses, poxviruses and some retroviruses encode dUTPase, an
      enzyme that can minimize the misincorporation of uracil into DNA. The encoding of
      dUTPase by these viruses also implies their importance in virus replication. An
      understanding at the molecular level of how these viruses replicate in non
      dividing cells should provide clues to the biological relevance of UNG and
      dUTPase function in virus replication.

PMID- 12237415
TI  - An investigation of incorporation of cellular antigens into vaccinia virus
      particles.
AB  - Vaccinia virus (VV) infection produces several types of virus particle called
      intracellular mature virus (IMV), intracellular enveloped virus (IEV), cell
      associated enveloped virus (CEV) and extracellular enveloped virus (EEV). Some
      cellular antigens are associated with EEV and these vary with the cell type used
      to grow the virus. To investigate if specific cell antigens are associated with
      VV particles, and to address the origin of membranes used to envelope IMV and
      IEV/CEV/EEV, we have studied whether cell antigens and foreign antigens expressed
      by recombinant VVs are incorporated into VV particles. Membrane proteins that are
      incorporated into the endoplasmic reticulum (ER), intermediate compartment (IC),
      cis/medial-Golgi, trans-Golgi network (TGN) or plasma membrane were not detected
      in purified IMV particles. In contrast, proteins present in the TGN or membrane
      compartments further downstream in the exocytic pathway co-purify with EEV
      particles when analysed by immunoblotting. Immunoelectron microscopy found only
      low levels of these proteins in IEV, CEV/EEV. The incorporation of foreign
      antigens into VV particles was not affected by loss of individual IEV or EEV
      specific proteins or by redirection of B5R to the ER. These data suggest that (i)
      host cell antigens are excluded from the lipid envelope surrounding the IMV
      particle and (ii) membranes of the ER, IC and cis/medial-Golgi are not used to
      wrap IMV particles to form IEV. Lastly, the VV haemagglutinin was absent from one
      third of IEV and CEV/EEV particles, whereas other EEV antigens were present in
      all these virions.

PMID- 12237416
TI  - Therapeutic vaccination with vhs(-) herpes simplex virus reduces the severity of
      recurrent herpetic stromal keratitis in mice.
AB  - Virion host shutoff (vhs)-deficient herpes simplex virus (HSV) was tested as a
      therapeutic vaccine in a mouse model of UV light-induced recurrent herpetic
      stromal keratitis. Four weeks after primary corneal infection, mice were
      vaccinated intraperitoneally with vhs(-) vaccine or control. Four weeks after
      vaccination, the eyes of latently infected mice were UV-B irradiated to induce
      recurrent virus shedding and disease. Post-irradiation corneal opacity in
      latently infected, vhs(-)-vaccinated mice was significantly reduced compared to
      control-vaccinated mice (P=0.007 to 0.035). The incidence and duration of
      recurrent virus shedding were the same in both groups. Antibody titres were
      increased (P=0.05) and delayed type hypersensitive responses were unaffected by
      vhs(-) vaccination. Combined with studies using different vaccination timing and
      vhs(-) genotypes, these data suggest that deletion of vhs is a useful strategy in
      the development of a therapeutic HSV vaccine, and that temporal and genetic
      factors influence vaccination outcome.

PMID- 12237417
TI  - A DNA vaccine containing an infectious Marek's disease virus genome can confer
      protection against tumorigenic Marek's disease in chickens.
AB  - A DNA vaccine containing the infectious BAC20 clone of serotype 1 Marek's disease
      virus (MDV) was tested for its potential to protect against Marek's disease (MD).
      Chickens were immunized at 1 day old with BAC20 DNA suspended either in PBS, as
      calcium phosphate precipitates, incorporated into chitosan nanoparticles, in
      Escherichia coli DH10B cells, or bound to gold particles for gene-gun delivery.
      Challenge infection with MDV strain EU1 was performed at 12 days old, and four
      out of seven birds immunized with BAC20 DNA in saline by the intramuscular route
      remained free of MD until day 77 after challenge infection. A delay in the
      development of the disease could be observed in some animals vaccinated with
      other BAC20 DNA formulations, but clinical MD and tumour formation were evident
      in all but one bird. Five out of seven animals immunized with the vaccine virus
      CVI988 were protected against MD, but none out of seven birds survived EU1
      challenge infection after injection of negative-control plasmid DNA. In a second
      animal experiment, five out of 12 chickens immunized with BAC20 DNA and six out
      of eight birds immunized with virus reconstituted from BAC20 DNA remained free of
      MD after challenge infection. In contrast, none out of 12 chickens survived
      challenge infection after immunization with BAC20 DNA lacking the essential gE
      gene or with gE-negative BAC20 virus. The results suggested that an MDV BAC DNA
      vaccine has potential to protect chickens against MD, but that in vivo
      reconstitution of vaccine virus is a prerequisite for protection.

PMID- 12237418
TI  - Epstein-Barr virus nuclear antigen-1 is highly colocalized with interphase
      chromatin and its newly replicated regions in particular.
AB  - Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1), which binds to both the EBV
      origin of replication (oriP) and metaphase chromosomes, is essential for the
      replication/retention and segregation/partition of oriP-containing plasmids. Here
      the chromosomal localization of EBNA-1 fused to green fluorescent protein (GFP
      EBNA-1) is examined by confocal microscopy combined with a 'premature chromosome
      condensation' (PCC) procedure. Analyses show that GFP-EBNA-1 expressed in living
      cells that lack oriP plasmids is associated with cellular chromatin that has been
      condensed rapidly by the PCC procedure into identifiable forms that are unique to
      each phase of interphase as well as metaphase chromosomes. Studies of cellular
      chromosomal DNAs labelled with BrdU or Cy3-dUTP indicate that GFP-EBNA-1
      colocalizes highly with the labelled, newly replicated regions of interphase
      chromatin in cells. These results suggest that EBNA-1 is associated not only with
      cellular metaphase chromosomes but also with condensing chromatin/chromosomes and
      probably with interphase chromatin, especially with its newly replicated regions.

PMID- 12237419
TI  - Characterization of a novel envelope protein (VP281) of shrimp white spot
      syndrome virus by mass spectrometry.
AB  - The primary structure of a novel envelope protein from shrimp white spot syndrome
      virus (WSSV) was characterized using a combination of SDS-PAGE and mass
      spectrometry. The resulting amino acid sequence matched an open reading frame
      (ORF), ORF1050, of the WSSV genome ORF database. ORF1050 contained 843 nt,
      encoding 281 aa, and was termed the vp281 gene. Computer-assisted analysis showed
      that both the vp281 gene and its product shared no significant homology with
      other known viruses. However, they shared striking identity/similarity with
      another WSSV structural protein, VP292, at both the nucleotide and amino acid
      sequence level, suggesting that vp281 and vp292 might have evolved by gene
      duplication from a common ancestral gene. WSSV VP281 cDNA was cloned into a
      pET32a(+) expression vector containing a T7 RNA polymerase promoter to produce
      (His)(6)-tagged fusion proteins in Escherichia coli strain BL21. Specific mouse
      antibodies were raised using the purified fusion protein (His)(6)-VP281. Western
      blot analysis showed that the mouse anti-(His)(6)-VP281 antibodies bound
      specifically to VP281 of WSSV, without cross-reactivity with VP292. The
      transmission electron microscope immunogold-labelling method was used to localize
      VP281 in the WSSV virion as an envelope protein. The cell attachment 'Arg-Gly
      Asp' motif in VP281 indicated that this protein might play an important role in
      mediating WSSV infectivity.

PMID- 12237420
TI  - Characterization of Campoletis sonorensis ichnovirus segment I genes as members
      of the repeat element gene family.
AB  - Campoletis sonorensis ichnovirus (CsIV) is a symbiotic virus associated with the
      endoparasitic wasp C. sonorensis. The virus is injected into the wasp's host,
      Heliothis virescens, during oviposition. One CsIV gene has been identified as a
      repeat element (rep) gene and encodes a ubiquitous imperfectly conserved 540 bp
      sequence. We report the sequencing and mapping of a rep-containing segment,
      segment I, that hybridizes to a known rep sequence from segment O(1). Analysis of
      this 8.6 kbp segment identified three ORFs having high similarity to the 540 bp
      rep sequence. All three rep sequence ORFs were expressed in parasitized H.
      virescens as well as in C. sonorensis tissues. Two of these rep genes, I 0.9 and
      I 1.1, have single copies of the 540 bp repeat sequence, while the third rep
      gene, I 1.2, has two imperfect copies, which are more similar to each other than
      to sequences on the segment I single-motif genes. Like the CsIV BHv 0.9 rep gene,
      the segment I rep genes lack introns and a signal peptide, suggesting that they
      are not secreted. Based on their similarity in nucleotide sequence, predicted
      amino acid sequence and gene structure, the three segment I repeat-containing
      genes, I 0.9, I 1.1 and I 1.2, are new members of the rep gene family.

PMID- 12237421
TI  - Genomic and phylogenetic analyses of an adenovirus isolated from a corn snake
      (Elaphe guttata) imply a common origin with members of the proposed new genus
      Atadenovirus.
AB  - Approximately 60% of the genome of an adenovirus isolated from a corn snake
      (Elaphe guttata) was cloned and sequenced. The results of homology searches
      showed that the genes of the corn snake adenovirus (SnAdV-1) were closest to
      their counterparts in members of the recently proposed new genus ATADENOVIRUS: In
      phylogenetic analyses of the complete hexon and protease genes, SnAdV-1 indeed
      clustered together with the atadenoviruses. The characteristic features in the
      genome organization of SnAdV-1 included the presence of a gene homologous to that
      for protein p32K, the lack of structural proteins V and IX and the absence of
      homologues of the E1A and E3 regions. These characteristics are in accordance
      with the genus-defining markers of atadenoviruses. Comparison of the cleavage
      sites of the viral protease in core protein pVII also confirmed SnAdV-1 as a
      candidate member of the genus ATADENOVIRUS: Thus, the hypothesis on the possible
      reptilian origin of atadenoviruses (Harrach, Acta Veterinaria Hungarica 48, 484
      490, 2000) seems to be supported. However, the base composition of DNA sequence
      (>18 kb) determined from the SnAdV-1 genome showed an equilibrated GC content of
      51%, which is unusual for an atadenovirus.

PMID- 12237422
TI  - Sequence of the 3'-terminal end (8.1 kb) of the genome of porcine
      haemagglutinating encephalomyelitis virus: comparison with other
      haemagglutinating coronaviruses.
AB  - A cytopathogenic coronavirus, serologically identified as porcine
      haemagglutinating encephalomyelitis virus (HEV), has recently been associated
      with acute outbreaks of wasting and encephalitis in nursing piglets from pig
      farms in southern Quebec and Ontario, Canada. The 3'-terminal end of the genome
      of the prototype HEV-67N strain and that of the recent Quebec IAF-404 field
      isolate, both propagated in HRT-18 cells, were sequenced. Overall, sequencing
      data indicated that HEV has remained antigenically and genetically stable since
      its first isolation in North America in 1962. Compared with the prototype strain
      of bovine enteropathogenic coronavirus (BCoV), HEV, as well as the human
      respiratory coronavirus (HCoV-OC43) showed a major deletion in their ORF4 gene.
      Deduced amino acid sequences for both HEV strains revealed 89/88, 80, 93/92 and
      95/94% identities with the structural proteins HE, S, M and N of BCoV and HCoV
      OC43, respectively. Major variations were observed in the S1 portion of the S
      gene of both HEV strains, with only 73/71% amino acid identities compared with
      those of the two other haemagglutinating coronaviruses.

PMID- 12237423
TI  - In vitro analysis of factors involved in the disassembly of Sindbis virus cores
      by 60S ribosomal subunits identifies a possible role of low pH.
AB  - Disassembly of alphavirus cores early in infection involves interaction of the
      core with 60S ribosomal subunits. This interaction might be subjected to
      regulatory processes. We have established an in vitro system of core disassembly
      in order to identify cellular proteins involved in the regulation of disassembly.
      No evidence for the existence of such proteins was found, but it became apparent
      that certain organic solvents and detergents or a high proton concentration (pH
      6.0) stimulated core disassembly. Alphaviruses infect cells by an endosomal
      pathway. The low pH in the endosome activates a fusion activity of the viral
      surface protein E1 and leads to fusion of the viral membrane with the endosomal
      membrane, followed by release of the core into the cytoplasm. Since the presence
      of the E1 protein in the plasma membrane of infected cells leads to increased
      membrane permeability at low pH, our findings indicate that disassembly of
      alphavirus cores could be regulated by the proton concentration. We propose that
      the viral membrane proteins present in the endosomal membrane after fusion form a
      pore, which allows the flow of protons from the endosome into the cytoplasm. This
      process would generate a region of low pH in the cytoplasm at the correct time
      and place to allow the efficient disassembly of the incoming viral core by 60S
      subunits.

PMID- 12237424
TI  - Infection of polarized epithelial cells with flavivirus West Nile: polarized
      entry and egress of virus occur through the apical surface.
AB  - Both polarized epithelial Vero (C1008) and non-polarized Vero (control) cells
      were grown on permeable cell culture inserts and infected either apically or
      basolaterally with West Nile (WN) or Kunjin (KUN) virus. KUN virus (closely
      related to WN virus) was used as a comparison. Using indirect immunofluorescence
      and plaque assays of productive virus titres, entry of WN and KUN viruses was
      confined to the apical surface of polarized epithelial cells. For the first time,
      these results provided evidence on the distribution of flavivirus-specific
      receptor(s) in polarized epithelial cells; that is to say that receptor
      expression was shown to be predominant at the apical surface. In addition, the
      release of these viruses from polarized Vero C1008 epithelial cells was also
      examined. Egress of WN virus strain Sarafend (S) was observed to occur
      predominantly at the apical surface of Vero C1008 cells. In contrast, the release
      of KUN virus was bi-directional from polarized Vero C1008 cells. Furthermore,
      disruption of the cellular microtubule network was shown to inhibit the apical
      release of WN (S) virus but had no effect on the release of KUN virus. Hence, the
      difference in the release of these closely related viruses suggested the
      involvement of a microtubule-dependent, polarized sorting mechanism for WN virus
      proteins but not for KUN virus proteins in polarized epithelial cells.

PMID- 12237425
TI  - Emergence of dengue virus type 4 genotype IIA in Malaysia.
AB  - Phylogenetic analyses of the envelope (E) gene sequence of five recently isolated
      dengue virus type 4 (DENV-4) suggested the emergence of a distinct geographical
      and temporal DENV-4 subgenotype IIA in Malaysia. Four of the isolates had direct
      ancestral lineage with DENV-4 Indonesia 1973 and showed evidence of intra
      serotypic recombination with the other recently isolated DENV-4, MY01-22713. The
      E gene of isolate MY01-22713 had strong evidence of an earlier recombination
      involving DENV-4 genotype II Indonesia 1976 and genotype I Malaysia 1969. These
      results suggest that intra-serotypic recombination amongst DENV-4 from
      independent ancestral lineages may have contributed to the emergence of DENV-4
      subgenotype IIA in Malaysia.

PMID- 12237426
TI  - Genome sequence analysis of Tamana bat virus and its relationship with the genus
      Flavivirus.
AB  - Tamana bat virus (TABV, isolated from the bat Pteronotus parnellii) is currently
      classified as a tentative species in the genus FLAVIVIRUS: We report here the
      determination and analysis of its complete coding sequence. Low but significant
      similarity scores between TABV and member-viruses of the genus Flavivirus were
      identified in the amino acid sequences of the structural, NS3 and NS5 genes. A
      series of cysteines located in the envelope protein and the most important
      enzymatic domains of the virus helicase/NTPase, methyltransferase and RNA
      dependent RNA polymerase were found to be highly conserved. In the serine
      protease domain, the catalytic sites were conserved, but variations in sequence
      were found in the putative substrate-binding sites, implying possible differences
      in the protease specificity. In accordance with this finding, the putative
      cleavage sites of the TABV polyprotein by the virus protease are substantially
      different from those of flaviviruses. The phylogenetic position of TABV could not
      be determined precisely, probably due to the extremely significant genetic
      divergence from other member-viruses of the family FLAVIVIRIDAE: However,
      analysis based on both genetic distances and maximum-likelihood confirmed that
      TABV is more closely related to the flaviviruses than to the other genera. These
      findings have implications for the evolutionary history and taxonomic
      classification of the family as a whole: (i) the possibility that flaviviruses
      were derived from viruses infecting mammals rather than from mosquito viruses
      cannot be excluded; (ii) using the current criteria for the definition of genera
      in the family Flaviviridae, TABV should be assigned to a new genus.

PMID- 12237427
TI  - Evidence of recombination in the capsid-coding region of type A foot-and-mouth
      disease virus.
AB  - Recombination is one of the factors that contribute to genetic diversity in foot
      and-mouth disease virus (FMDV). Similarity and bootscan analyses have provided
      evidence of recombination in the capsid-coding (P1) region of the virus. In the
      present study, of the 14 subtype A22 field isolates that were distributed in
      three previously described genotypes (IV, VI and VII) based on the 1D (VP1
      encoding) gene sequence (Tosh et al., 2002 ), one isolate (IND 170/88) was found
      to be a hybrid of genotypes VI and VII in the P1 region. VP1, VP4, the 5' region
      of VP2 and the 3' region of VP3 of this virus were characteristic of genotype VI,
      whereas the remaining 3' region of VP2 and the 5' region of VP3 were
      characteristic of genotype VII. No insertion or deletion was observed in the
      recombinant virus. Recombination in the P1 region may provide an escape mechanism
      for the virus.

PMID- 12237428
TI  - Molecular epidemiology of Rabbit haemorrhagic disease virus.
AB  - Millions of domestic and wild European rabbits (Oryctolagus cuniculus) have died
      in Europe, Asia, Australia and New Zealand during the past 17 years following
      infection by Rabbit haemorrhagic disease virus (RHDV). This highly contagious and
      deadly disease was first identified in China in 1984. Epidemics of RHDV then
      radiated across Europe until the virus apparently appeared in Britain in 1992.
      However, this concept of radiation of a new and virulent virus from China is not
      entirely consistent with serological and molecular evidence. This study shows,
      using RT-PCR and nucleotide sequencing of RNA obtained from the serum of healthy
      rabbits stored at 4 degrees C for nearly 50 years, that, contrary to previous
      opinions, RHDV circulated as an apparently avirulent virus throughout Britain
      more than 50 years ago and more than 30 years before the disease itself was
      identified. Based on molecular phylogenetic analysis of British and European RHDV
      sequences, it is concluded that RHDV has almost certainly circulated harmlessly
      in Britain and Europe for centuries rather than decades. Moreover, analysis of
      partial capsid sequences did not reveal significant differences between RHDV
      isolates that came from either healthy rabbits or animals that had died with
      typical haemorrhagic disease. The high stability of RHDV RNA is also demonstrated
      by showing that it can be amplified and sequenced from rabbit bone marrow samples
      collected at least 7 weeks after the animal has died.

PMID- 12237429
TI  - Interference of the life cycle of fish nodavirus with fish retrovirus.
AB  - Interference of the life cycle of grouper nervous necrosis virus (GNNV), a member
      of the Nodaviridae, genus Betanodavirus, by snakehead retrovirus (SnRV) has been
      studied in vitro. SGF-1, a new fish cell line that is persistently infected with
      SnRV, was induced by inoculating SnRV into the grouper fin cell line GF-1.
      Culture supernatants and cell pellets from both GNNV-infected SGF-1 and GF-1
      cells were collected and employed for virus productivity analysis. The yields of
      GNNV RNA and capsid protein in GNNV-infected SGF-1 cells were similar to those in
      GNNV-infected GF-1 cells. However, when GF-1 cells were used for titration, the
      titre of the culture supernatant from GNNV-infected SGF-1 cells was much higher
      than that from GNNV-infected GF-1 cells. The titration result suggested that SnRV
      enhanced the infection or cytopathic effect (CPE) of GNNV during GNNV and SnRV
      coinfection of the GF-1 cell titration system, although SnRV cannot induce any
      CPE in GF-1 cells alone, nor can it increase the yield of GNNV after GNNV
      superinfection of SGF-1 cells. Moreover, GNNV cDNA was detected in both the
      pellet and the supernatant from GNNV-infected SGF-1 cells. This result indicated
      that SnRV reverse-transcribed the GNNV single-stranded genomic RNA into cDNA
      during GNNV superinfection of SGF-1 cells and created a new cDNA stage in the
      life cycle of the fish nodavirus.

PMID- 12237430
TI  - Full-length genome analysis of natural isolates of vesicular stomatitis virus
      (Indiana 1 serotype) from North, Central and South America.
AB  - Most studies on the molecular biology and functional analysis of vesicular
      stomatitis virus Indiana 1 serotype (VSV-IN1) are based on the only full-length
      genomic sequence currently deposited in GenBank. This sequence is a composite of
      several VSV-IN1 laboratory strains passaged extensively in tissue culture over
      the years and it is not certain that this sequence is representative of strains
      circulating in nature. We describe here the complete genomic sequence of three
      natural isolates, each representing a distinct genetic lineage and geographical
      origin: 98COE (North America), 94GUB (Central America) and 85CLB (South America).
      Genome structure and organization were conserved, with a 47 nucleotide 3' leader,
      five viral genes -- N, P, M, G and L -- and a 59 nucleotide 5' trailer. The most
      conserved gene was N, followed by M, L and G, with the most variable being P.
      Sequences containing the polyadenylation and transcription stop and start signals
      were completely conserved among all the viruses studied, but changes were found
      in the non-transcribed intergenic nucleotides, including the presence of a
      trinucleotide at the M-G junction of the South American lineage isolate. A 102
      189 nucleotide insertion was present in the 5' non-coding region of the G gene
      only in the viruses within a genetic lineage from northern Central America. These
      full-length genomic sequences should be useful in designing diagnostic probes and
      in the interpretation of functional genomic analyses using reverse genetics.

PMID- 12237431
TI  - Detection of measles virus genome in bone-marrow aspirates from adults.
AB  - We investigated the presence of the measles virus genome in order to identify
      asymptomatic infections in the adult population. Bone-marrow aspirates were
      obtained from 179 patients, 20-96 years of age, for the diagnosis of malignant
      diseases (29 with malignant lymphoma, 28 with acute leukaemia, 21 with
      myelodysplastic syndrome, five with multiple myeloma and 96 with other diseases).
      The measles virus genome was detected in 17 (9.5%) of 179 individuals by RT-PCR
      and 28 (15.6%) through hybridization. The genomes detected in bone marrow were
      all in the same cluster, D5, the strain circulating during the study period, and
      no evidence of persistent infection was obtained. We conclude that asymptomatic
      infections of measles virus are common in adults and the presence of the measles
      virus genome would not be related to the pathogenesis of illness.

PMID- 12237432
TI  - Antigenic relationships between six genotypes of the small hydrophobic protein
      gene of mumps virus.
AB  - Six different genotypes of mumps virus, A, C, D, G, H and I, genotyped on the
      basis of the small hydrophobic protein gene sequence, were subjected to antigenic
      comparison. Monoclonal antibodies directed against the haemagglutinin
      neuraminidase protein of the SBL-1 strain of genotype A were used in
      immunofluorescence tests with different mumps virus strains. In addition, the six
      virus genotypes were compared by cross-neutralization tests with human post
      vaccination sera after vaccination with the Jeryl Lynn (JL) strain of mumps virus
      and with rabbit hyperimmune sera directed against the A or D genotypes of mumps
      virus. Genotypes C, D, G, H and I could not be antigenically separated. In
      contrast, three different virus strains of genotype A, SBL-1, JL and Kilham, were
      distinct and were found to represent three different serotypes within the A
      genotype of mumps virus. Vaccination of Swedish children with the JL strain of
      mumps virus resulted in clearly lower neutralization titres against the SBL-1
      strain, which is endemic in Sweden, compared to the homologous vaccine titres.

PMID- 12237434
TI  - Initiation of hepatitis delta virus (HDV) replication: HDV RNA encoding the large
      delta antigen cannot replicate.
AB  - The hepatitis delta virus (HDV) nucleocapsid consists of a genomic-length RNA of
      1.7 kb and approximately equimolar amounts of the small and large forms of the
      hepatitis delta antigen (S-HDAg and L-HDAg, respectively). Since HDV RNA
      particles contain not only a genomic RNA species encoding S-HDAg but also an RNA
      species encoding L-HDAg, which is produced by an RNA-editing process, the
      question arises as to whether RNAs encoding either L-HDAg or S-HDAg can initiate
      replication. To study this, two cDNA-free transfection methods were employed: HDV
      RNA cotransfected with either the S-HDAg-encoding mRNA species or the
      ribonucleocapsid protein complex, comprising HDV RNA and recombinant S-HDAg.
      Results showed that the genomic-sense RNA encoding S-HDAg could promote HDV
      replication, whereas the L-HDAg-encoding RNA species was unable to replicate
      under the same conditions. The antigenomic RNA species encoding either S-HDAg or
      L-HDAg could not replicate by either of these procedures. In addition, L-HDAg
      alone could not promote replication of the genomic RNA but, by supplementing an
      equal amount of S-HDAg, replication occurred. These data indicate that L-HDAg
      encoding RNA species are probably not involved in the initiation of HDV RNA
      synthesis; instead, their main function may be to serve as template for producing
      L-HDAg, which regulates HDV RNA synthesis and virion assembly. These results
      suggest that the genomic RNA species encoding S-HDAg is the only functional
      genome for HDV infection and explain why the presence of the edited HDV RNA
      encoding L-HDAg does not interfere with HDV infection.

PMID- 12237433
TI  - Structure of antigenic sites on the haemagglutinin molecule of H5 avian influenza
      virus and phenotypic variation of escape mutants.
AB  - To elucidate the structure of the antigenic sites of avian H5 influenza virus
      haemagglutinin (HA) we analysed escape mutants of a mouse-adapted variant of the
      H5N2 strain A/Mallard/Pennsylvania/10218/84. A panel of five anti-H5 monoclonal
      antibodies (mAbs) was used to select 16 escape mutants. The mutants were tested
      by ELISA and haemagglutination inhibition with this panel of anti-H5 mAbs and the
      HA genes of the mutants were sequenced. The sequencing demonstrated that the
      amino acid changes were grouped in two antigenic sites. One corresponded to site
      A in the H3 HA. The other contained areas that are separated in the amino acid
      sequence but are topographically close in the three-dimensional structure and
      partially overlap in the reactions with mAbs. This site corresponds in part to
      site B in the H3 structure; it also includes a region not involved in site B that
      partially overlaps site Sa in the H1 HA and an antigenic area in H2 HA. Mutants
      with the amino acid change K152N, as well as those with the change D126N, showed
      reduced lethality in mice. The substitution D126N, creating a new glycosylation
      site, was accompanied by an increase in the sensitivity of the mutants to normal
      mouse serum inhibitors. Several amino acid changes in the H5 escape mutants
      occurred at the positions of reported changes in H2 drift variants. This
      coincidence suggests that the antigenic sites described and analysed here may be
      important for drift variation if H5 influenza virus ever appears as a pathogen
      circulating in humans.

PMID- 12237435
TI  - Lymphoid activation: a confounding factor in AIDS vaccine development?
AB  - In a previous vaccination trial, inoculation of env gene DNA failed to elicit a
      detectable antibody response, yet accelerated virus dissemination in most
      immunized cats following challenge with feline immunodeficiency virus. This
      result raised the possibility that cell-mediated immune responses had given rise
      to immune-mediated enhancement of infection. Since high-level replication of
      immunodeficiency viruses in lymphocytes requires cellular activation, antigen
      specific responses or non-specific polyclonal activation may have increased the
      frequency of optimal target cells. In the present DNA vaccination trial, although
      designed so as to minimize non-specific polyclonal activation, immune-mediated
      enhancement was nonetheless observed in certain immunized cats. Moreover, rapid
      virus dissemination in vivo was associated with the presence of T-helper
      responses prior to challenge, and was linked to increased susceptibility of
      lymphocytes to ex vivo infection. Immune activation may thus be a confounding
      factor in vaccination against lentivirus infection, diminishing vaccine efficacy
      and giving rise to immune-mediated enhancement.

PMID- 12237436
TI  - Characterization of a human immunodeficiency virus type 1 pre-integration complex
      in which the majority of the cDNA is resistant to DNase I digestion.
AB  - The human immunodeficiency virus type 1 (HIV-1) pre-integration complex (PIC) is
      a cytoplasmic nucleoprotein structure derived from the core of the virion and is
      responsible for reverse transcription of viral RNA to cDNA, transport to the
      nucleus and integration of the cDNA into the genome of the infected target cell.
      Others have shown by Mu phage-mediated PCR footprinting that only the LTRs of the
      cDNA of PICs isolated early in infection are protected by bound protein, while
      the rest of the genome is susceptible to nuclease attack. Here, using DNase I
      footprinting, we confirmed that the majority of the cDNA of PICs isolated at 8.5
      h after infection with cell-free virus was sensitive to digestion with DNase I
      and that only part of the LTRs (approximately 6% of the total cDNA) was
      protected. However, PICs isolated 90 min later (at 10 h post-infection) were very
      different in that the majority (approximately 90%) of cDNA was protected from
      nuclease degradation. These late PICs were integration active in vitro. We
      conclude that HIV-1 has at least two types of PIC, an early PIC characterized by
      protein bound only at the LTRs, and a late, and possibly more mature form, in
      which protein is bound along the length of the cDNA.

PMID- 12237437
TI  - Requirements for RNA heterodimerization of the human immunodeficiency virus type
      1 (HIV-1) and HIV-2 genomes.
AB  - Retroviruses are prone to recombination because they package two copies of the
      RNA genome. Whereas recombination is a frequent event within the human
      immunodeficiency virus type 1 (HIV-1) and HIV-2 groups, no HIV-1/HIV-2
      recombinants have been reported thus far. The possibility of forming HIV-1/HIV-2
      RNA heterodimers was studied in vitro. In both viruses, the dimer initiation site
      (DIS) hairpin is used to form dimers, but these motifs appear too dissimilar to
      allow RNA heterodimer formation. Multiple mutations were introduced into the HIV
      2 DIS element to gradually mimic the HIV-1 hairpin. First, the loop-exposed
      palindrome of HIV-1 was inserted. This self-complementary sequence motif forms
      the base pair interactions of the kissing-loop (KL) dimer complex, but such a
      modification is not sufficient to permit RNA heterodimer formation. Next, the HIV
      2 DIS loop size was shortened from 11 to 9 nucleotides, as in the HIV-1 DIS
      motif. This modification also results in the presentation of the palindromes in
      the same position within the hairpin loop. The change yielded a modest level of
      RNA heterodimers, which was not significantly improved by additional sequence
      changes in the loop and top base pair. No isomerization of the KL dimer to the
      extended duplex dimer form was observed for the heterodimers. These combined
      results indicate that recombination between HIV-1 and HIV-2 is severely
      restricted at the level of RNA dimerization.

PMID- 12237438
TI  - Selection of antigenic variants in maedi-visna virus infection.
AB  - In order to analyse the pattern of sequence variation in maedi-visna virus (MVV)
      in persistently infected sheep and to answer the question of whether antigenic
      variants are selected in a long-term MVV infection, an 87 bp variable region in
      the env gene of ten antigenic variants and 24 non-variants was sequenced. Nine of
      the ten antigenic variants had mutations in this region, comprising 24 point
      mutations and a deletion of 3 bp. Twenty-three of the point mutations (96%) were
      non-synonymous. There was only a single mutation in this region in the 24 non
      variants. A type-specific neutralizing antibody response appeared in all the
      sheep 2-5 months post-infection, and in most sheep more broadly reacting
      neutralizing antibodies appeared up to 4 years later. All the antigenic variants
      were neutralized by the broadly reacting sera. It is noteworthy that the
      antigenic variants were isolated at a time when only the type-specific antibodies
      were acting, before the broadly reacting antibodies appeared. The same picture
      emerged when molecularly cloned virus was used for infection. Three sheep were
      infected with a molecularly cloned virus, and of six virus isolates, one was an
      antigenic variant. This variant arose in the absence of broadly reacting
      antibodies. The results indicate that there is selection for mutants that escape
      neutralization.

PMID- 12237439
TI  - The viral envelope is a major determinant for the induction of lymphoid and
      myeloid tumours by avian leukosis virus subgroups A and J, respectively.
AB  - Among the six envelope subgroups of avian leukosis virus (ALV) that infect
      chickens, subgroups A (ALV-A) and J (ALV-J) are the most pathogenic and
      widespread among commercial chicken populations. While ALV-A is predominantly
      associated with lymphoid leukosis (LL) and less frequently with erythroblastosis
      (EB), ALV-J mainly induces tumours of the myeloid lineage. In order to examine
      the basis for the lineage specificity of tumour induction by these two ALV
      subgroups, we constructed two chimeric viruses by substituting the env genes into
      the reciprocal proviral clones. The chimeric HPRS-103(A) virus carrying the
      subgroup A env gene is identical to ALV-J prototype virus HPRS-103 except for the
      env gene, and the chimeric RCAS(J) virus carrying the subgroup J env gene is
      identical to the parent replication-competent ALV-A vector RCAS except for the
      env gene. In experimentally inoculated chickens, HPRS-103(A) virus induced LL and
      EB similar to ALV-A isolates such as RAV-1, while RCAS(J) virus induced myeloid
      leukosis (ML) and EB, similar to ALV-J, suggesting that the env gene is the major
      determinant for the lineage-specific oncogenicity. There were genetic differences
      in susceptibility to tumour induction between line 0 and line 15(I) chickens,
      indicating that in addition to the env gene, other viral or host factors could
      also serve as determinants for oncogenicity. Induction of both LL and ML by the
      two chimeric viruses occurred through the activation of c-myc, while the EB
      tumours were induced by activation of the c-erbB oncogene.

PMID- 12237440
TI  - Evidence for diversifying selection in Potato virus Y and in the coat protein of
      other potyviruses.
AB  - The modes of evolution of the proteins of Potato virus Y were investigated with a
      maximum-likelihood method based on estimation of the ratio between non-synonymous
      and synonymous substitution rates. Evidence for diversifying selection was
      obtained for the 6K2 protein (one amino acid position) and coat protein (24 amino
      acid positions). Amino acid sites in the coat proteins of other potyviruses (Bean
      yellow mosaic virus, Yam mosaic virus) were also found to be under diversifying
      selection. Most of the sites belonged to the N-terminal domain, which is exposed
      to the exterior of the virion particle. Several of these amino acid positions in
      the coat proteins were shared between some of these three potyviruses.
      Identification of diversifying selection events in these different proteins will
      help to unravel their biological functions and is essential to an understanding
      of the evolutionary constraints exerted on the potyvirus genome. The hypothesis
      of a link between evolutionary constraints due to host plants and occurrence of
      diversifying selection is discussed.

PMID- 12237441
TI  - On the evolution and molecular epidemiology of the potyvirus Papaya ringspot
      virus.
AB  - The potyvirus Papaya ringspot virus (PRSV) is found throughout the tropics and
      subtropics. Its P biotype is a devastating pathogen of papaya crops and its W
      biotype of cucurbits. PRSV-P is thought to arise by mutation from PRSV-W.
      However, the relative impact of mutation and movement on the structure of PRSV
      populations is not well characterized. To investigate this, we have determined
      the coat protein sequences of isolates of both biotypes of PRSV from Vietnam
      (50), Thailand (13), India (1) and the Philippines (1), and analysed them
      together with 28 PRSV sequences already published, so that we can better
      understand the molecular epidemiology and evolution of PRSV. In Thailand,
      variation was greater among PRSV-W isolates (mean nucleotide divergence 7.6%)
      than PRSV-P isolates (mean 2.6%), but in Vietnamese populations the P and W
      biotypes were more but similarly diverse. Phylogenetic analyses of PRSV also
      involving its closest known relative, Moroccan watermelon mosaic virus, indicate
      that PRSV may have originated in Asia, particularly in the Indian subcontinent,
      as PRSV populations there are most diverse and hence have probably been present
      longest. Our analyses show that mutation, together with local and long-distance
      movement, contributes to population variation, and also confirms an earlier
      conclusion that populations of the PRSV-P biotype have evolved on several
      occasions from PRSV-W populations.

PMID- 12237442
TI  - Low genetic variation between isolates of Citrus leaf blotch virus from different
      host species and of different geographical origins.
AB  - The population structure and genetic diversity of Citrus leaf blotch virus (CLBV)
      were estimated by single-strand conformation polymorphism and nucleotide sequence
      analyses of two genomic regions located within the replicase (R) and the coat
      protein (C) genes. Analysis of 30 cDNA clones of each genomic region from two
      CLBV isolates showed that both isolates contained a predominant haplotype and
      others closely related. Analysis of 37 CLBV Spanish field isolates showed low
      genetic diversity (0.0041 and 0.0018 for genomic regions R and C, respectively).
      Comparison of 14 CLBV isolates from Spain, Japan, USA, France and Australia
      showed genetic diversities of 0.0318 (R) and 0.0209 (C), respectively. No
      correlation was found between genetic distance and geographical origin or host
      species of the isolates. The ratio between nonsynonymous and synonymous
      substitutions was the lowest found in a plant virus, indicating a strong negative
      selective pressure in both genomic regions.

PMID- 12237443
TI  - Molecular structures of viruses from Raman optical activity.
AB  - A vibrational Raman optical activity (ROA) study of a range of different
      structural types of virus exemplified by filamentous bacteriophage fd, tobacco
      mosaic virus, satellite tobacco mosaic virus, bacteriophage MS2 and cowpea mosaic
      virus has revealed that, on account of its sensitivity to chirality, ROA is an
      incisive probe of their aqueous solution structures at the molecular level.
      Protein ROA bands are especially prominent from which, as we have shown by
      comparison with the ROA spectra of proteins with known structures and by using a
      pattern recognition program, the folds of the major coat protein subunits may be
      deduced. Information about amino acid side-chain conformations, exemplified here
      by the determination of the sign and magnitude of the torsion angle chi(2,1) for
      tryptophan in fd, may also sometimes be obtained. By subtracting the ROA spectrum
      of the empty protein capsid (top component) of cowpea mosaic virus from those of
      the intact middle and bottom-upper components separated by means of a caesium
      chloride density gradient, the ROA spectrum of the viral RNA was obtained, which
      revealed that the RNA takes up an A-type single-stranded helical conformation and
      that the RNA conformations in the middle and bottom-upper components are very
      similar. This information is not available from the X-ray crystal structure of
      cowpea mosaic virus since no nucleic acid is visible.

PMID- 12237444
TI  - Various morphological aspects of Escherichia coli lysis by two distinct RNA
      bacteriophages.
AB  - Transmission electron micrographs of Escherichia coli cells induced by cloned
      lysis genes from RNA bacteriophages GA (group A-II) and SP (group B-IV) revealed
      various morphological aspects of intermediates of lysing cells. Cells induced by
      the SP lysis gene became stretched and also tapered in shape and fragmentation of
      parts of the cells had also occurred. Cells induced by the GA lysis gene showed
      many ballooning structures on the cell surfaces and others leaked material
      through the cell wall. Some balloon-like structures also appeared on the surfaces
      of cells induced by the cloned lysis gene of RNA phage SP and material also
      appeared to be leaking through the cell wall in the photographs. The lysing cells
      observed by transmission electron microscopy showed various morphological aspects
      of intermediates of the lysing process.

PMID- 12237445
TI  - PrP(Sc) accumulation in placentas of ewes exposed to natural scrapie: influence
      of foetal PrP genotype and effect on ewe-to-lamb transmission.
AB  - Placentas from scrapie-affected ewes are known to be infectious. Nevertheless,
      placenta infectivity in such ewes is not systematic. Maternal transmission to
      lambs is highly suspected but contamination of the foetus in utero has not been
      demonstrated. Using ewes from a naturally scrapie-infected flock, it was
      demonstrated that abnormal prion protein (PrP(Sc)) accumulation in the placenta
      (i) is controlled by polymorphisms at codons 136, 154 and 171 of the foetal PrP
      gene and (ii) is restricted mainly to placentome foetal trophoblastic cells. In
      order to go deeper into the role of the placenta in scrapie transmission, the
      pattern of PrP(Sc) dissemination was established in susceptible lambs (genotype
      VRQ/VRQ) sampled from 140 days post-insemination to the age of 4 months from
      either VRQ/VRQ ewes with PrP(Sc)-positive placentas or ARR/VRQ ewes with PrP(Sc)
      negative placentas. In both VRQ/VRQ lamb groups, PrP(Sc) spatial and temporal
      accumulation patterns were similar, suggesting post-natal rather than in utero
      contamination.

PMID- 12237446
TI  - PrP(CWD) lymphoid cell targets in early and advanced chronic wasting disease of
      mule deer.
AB  - Up to 15% of free-ranging mule deer in northeastern Colorado and southeastern
      Wyoming, USA, are afflicted with a prion disease, or transmissible spongiform
      encephalopathy (TSE), known as chronic wasting disease (CWD). CWD is similar to a
      subset of TSEs including scrapie and variant Creutzfeldt-Jakob disease in which
      the abnormal prion protein isoform, PrP(CWD), accumulates in lymphoid tissue.
      Experimental scrapie studies have indicated that this early lymphoid phase is an
      important constituent of prion replication interposed between mucosal entry and
      central nervous system accumulation. To identify the lymphoid target cells
      associated with PrP(CWD), we used triple-label immunofluorescence and high
      resolution confocal microscopy on tonsils from naturally infected deer in
      advanced disease. We detected PrP(CWD) primarily extracellularly in association
      with follicular dendritic and B cell membranes as determined by frequent co
      localization with antibodies against membrane bound immunoglobulin and CD21.
      There was minimal co-localization with cytoplasmic labels for follicular
      dendritic cells (FDC). This finding could indicate FDC capture of PrP(CWD),
      potentially in association with immunoglobulin or complement, or PrP(C)
      conversion on FDC. In addition, scattered tingible body macrophages in the
      germinal centre contained coarse intracytoplasmic aggregates of PrP(CWD),
      reflecting either phagocytosis of PrP(CWD) on FDC processes, apoptotic FDC or B
      cells, or actual PrP(CWD) replication within tingible body macrophages. To
      compare lymphoid cell targets in early and advanced disease, we also examined:
      (i) PrP(CWD) distribution in lymphoid cells of fawns within 3 months of oral CWD
      exposure and (ii) tonsil biopsies from preclinical deer with naturally acquired
      CWD. These studies revealed that the early lymphoid cellular distribution of
      PrP(CWD) was similar to that in advanced disease, i.e. in a pattern suggesting
      FDC association. We conclude that in deer, PrP(CWD) accumulates primarily
      extracellularly and associated with FDCs and possibly B cells - a finding which
      raises questions as to the cells responsible for pathological prion production.

PMID- 12237447
TI  - Preclinical diagnosis of chronic wasting disease in captive mule deer (Odocoileus
      hemionus) and white-tailed deer (Odocoileus virginianus) using tonsillar biopsy.
AB  - The usefulness of tonsillar biopsy on live deer for preclinical diagnosis of the
      transmissible spongiform encephalopathy chronic wasting disease (CWD) was
      evaluated. Disease was tracked in a CWD-endemic herd using serial tonsillar
      biopsies collected at 6 to 9 month intervals from 34 captive mule deer
      (Odocoileus hemionus) and five white-tailed deer (O. virginianus). Tonsillar
      biopsies were examined for accumulation of PrP(CWD), the protein marker for
      infection, using immunohistochemical (IHC) staining. 26/34 (76%) mule deer and
      4/5 (80%) white-tailed deer had PrP(CWD) accumulation in tonsillar biopsies; CWD
      was subsequently confirmed by post-mortem examination in all 30 of these
      tonsillar-positive deer. Six mule deer with IHC-negative tonsillar biopsies had
      positive brain and tonsillar IHC staining upon death 12 to 40 months following
      the last biopsy. PrP(CWD) accumulation in tonsillar biopsy was observed 2 to 20
      months before CWD-related death and up to 14 months before onset of clinical
      signs of CWD. Tonsillar biopsies from 3-month-old mule deer (n=6) were IHC
      negative, but PrP(CWD) accumulation was detected in tonsillar biopsies from 7/10
      mule deer by 19 months of age. Tonsillar biopsy evaluated with IHC staining is a
      useful technique for the preclinical diagnosis of CWD in live mule deer and white
      tailed deer when intensive management approaches are possible.

PMID- 12237449
TI  - Nuclear lipid signaling.
AB  - Abundant evidence now supports the existence of phospholipids in the nucleus that
      resist washing of nuclei with detergents. These lipids are apparently not in the
      nuclear envelope as part of a bilayer membrane, but are actually within the
      nucleus in the form of proteolipid complexes with unidentified proteins. This
      review discusses the experimental evidence that attempts to explain their
      existence. Among these nuclear lipids are the polyphosphoinositol lipids which,
      together with the enzymes that synthesize them, form an intranuclear
      phospholipase C (PI-PLC) signaling system that generates diacylglycerol (DAG) and
      inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. The isoforms of PI-PLC that are
      involved in this signaling system, and how they are regulated, are not yet
      entirely clear. Generation of DAG within the nucleus is believed to recruit
      protein kinase C (PKC) to the nucleus to phosphorylate intranuclear proteins.
      Generation of Ins(1,4,5)P3 may mobilize Ca2+ from the space between the nuclear
      membranes and thus increase nucleoplasmic Ca2+. Less well understood are the
      increasing number of variations and complications on the "simple" idea of a PI
      PLC system. These include, all apparently within the nucleus, (i) two routes of
      synthesis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]; (ii) two
      sources of DAG, one from the PI-PLC pathway and the other probably from
      phosphatidylcholine; (iii) several isoforms of PKC translocating to nuclei; (iv)
      increases in activity of the PI-PLC pathway at two points in the cell cycle; (v)
      a pathway of phosphorylation of Ins(1,4,5)P3, which may have several functions,
      including a role in the transfer of mRNA out of the nucleus; and (vi) the
      possible existence of other lipid signaling pathways that may include
      sphingolipids, phospholipase A2, and, in particular, 3-phosphorylated inositol
      lipids, which are now emerging as possible major players in nuclear signaling.

PMID- 12237450
TI  - A CH domain-containing N terminus in NuMA?
AB  - Nuclear mitotic apparatus protein (NuMA) is an essential vertebrate component in
      organizing microtubule ends at spindle poles. The NuMA-dynactin/dynein motor
      multiprotein complex not only explains the transport of NuMA along spindle fibers
      but also is linked to the process of microtubule focusing. The interaction sites
      of NuMA to dynein/dynactin have not been mapped. In the yet functionally
      uncharacterized N terminus of NuMA, we predict a calponin-homology (CH) domain, a
      motif with binding activity for actin-like molecules. We substantiate the primary
      sequence analysis-based prediction with secondary structure and fold recognition
      analysis, and we propose the N-terminal CH domain of NuMA as a likely interaction
      site for actin-related protein 1 (Arp1) protein of the dynactin/dynein complex.

PMID- 12237451
TI  - CxxS: fold-independent redox motif revealed by genome-wide searches for
      thiol/disulfide oxidoreductase function.
AB  - Redox reactions involving thiol groups in proteins are major participants in
      cellular redox regulation and antioxidant defense. Although mechanistically
      similar, thiol-dependent redox processes are catalyzed by structurally distinct
      families of enzymes, which are difficult to identify by available protein
      function prediction programs. Herein, we identified a functional motif, CxxS
      (cysteine separated from serine by two other residues), that was often conserved
      in redox enzymes, but rarely in other proteins. Analyses of complete Escherichia
      coli, Campylobacter jejuni, Methanococcus jannaschii, and Saccharomyces
      cerevisiae genomes revealed a high proportion of proteins known to use the CxxS
      motif for redox function. This allowed us to make predictions in regard to redox
      function and identity of redox groups for several proteins whose function
      previously was not known. Many proteins containing the CxxS motif had a
      thioredoxin fold, but other structural folds were also present, and CxxS was
      often located in these proteins upstream of an alpha-helix. Thus, a conserved
      CxxS sequence followed by an alpha-helix is typically indicative of a redox
      function and corresponds to thiol-dependent redox sites in proteins. The data
      also indicate a general approach of genome-wide identification of redox proteins
      by searching for simple conserved motifs within secondary structure patterns.

PMID- 12237452
TI  - Conformational transition states of a beta-hairpin peptide between the ordered
      and disordered conformations in explicit water.
AB  - The conformational transition states of a beta-hairpin peptide in explicit water
      were identified from the free energy landscapes obtained from the multicanonical
      ensemble, using an enhanced conformational sampling calculation. The beta-hairpin
      conformations were significant at 300 K in the landscape, and the typical nuclear
      Overhauser effect signals were reproduced, consistent with the previously
      reported experiment. In contrast, the disordered conformations were predominant
      at higher temperatures. Among the stable conformations at 300 K, there were
      several free energy barriers, which were not visible in the landscapes formed
      with the conventional parameters. We identified the transition states around the
      saddle points along the putative folding and unfolding paths between the beta
      hairpin and the disordered conformations in the landscape. The characteristic
      features of these transition states are the predominant hydrophobic contacts and
      the several hydrogen bonds among the side-chains, as well as some of the backbone
      hydrogen bonds. The unfolding simulations at high temperatures, 400 K and 500 K,
      and their principal component analyses also provided estimates for the transition
      state conformations, which agreed well with those at 400 K and 500 K deduced from
      the current free energy landscapes at 400 K and 500 K, respectively. However, the
      transition states at high temperatures were much more widely distributed on the
      landscape than those at 300 K, and their conformations were different.

PMID- 12237453
TI  - How do two unrelated antibodies, HyHEL-10 and F9.13.7, recognize the same epitope
      of hen egg-white lysozyme?
AB  - The anti-hen egg-white lysozyme (HEWL) antibodies HyHEL-10 and F9.13.7 recognize
      a common epitope. The structures of the complexes differ, however, in the numbers
      of electrostatic and hydrogen-bond interactions and in the distributions of
      contacts between the light and heavy chains. The equilibria and kinetics
      characterizing the F9.13.7 complex formation were evaluated for both wild-type
      and mutant derivatives of HEWL to help to understand how the different contacts
      are effectively used in the complexes with the two antibodies. Three epitope hot
      spots, Y20, K96, and R73 (destabilization > 4 kcal/mole), were found by alanine
      scanning mutagenesis. The first two constitute two of the three hot spots in the
      HyHEL-10 complex. The hot spots of the HyHEL-10 paratope are centered on the HEWL
      epitope; whereas R73 (HEWL), the only important light-chain-contacting residue,
      is clearly separated from the other hot spots of the F9.13.7 complex. The larger
      number of epitope warm plus hot spots found in the F9.13.7 complex compared with
      that of HyHEL-10 shows that the specificity of the former is greater even though
      the K(D) value is 20-fold larger. Conservative mutations showed that the
      specificity enhancement is related to the greater number of functional polar and
      hydrogen bond interactions in the F9.13.7 complex. Alanine scanning mutagenesis
      would not have illuminated these distinctions. It is shown that the concept of
      antigen specificity, as defined by cross-reactivity with natural variant
      antigens, is flawed by phylogenetic bias, and that specificity can only be
      defined by the use of unbiased epitopes, which are conveniently accessed by site
      directed mutagenesis.

PMID- 12237454
TI  - Characterization of binding-induced changes in dynamics suggests a model for
      sequence-nonspecific binding of ssDNA by replication protein A.
AB  - Single-stranded-DNA-binding proteins (SSBs) are required for numerous genetic
      processes ranging from DNA synthesis to the repair of DNA damage, each of which
      requires binding with high affinity to ssDNA of variable base composition. To
      gain insight into the mechanism of sequence-nonspecific binding of ssDNA, NMR
      chemical shift and (15)N relaxation experiments were performed on an isolated
      ssDNA-binding domain (RPA70A) from the human SSB replication protein A. The
      backbone (13)C, (15)N, and (1)H resonances of RPA70A were assigned for the free
      protein and the d-CTTCA complex. The binding-induced changes in backbone chemical
      shifts were used to map out the ssDNA-binding site. Comparison to results
      obtained for the complex with d-C(5) showed that the basic mode of binding is
      independent of the ssDNA sequence, but that there are differences in the binding
      surfaces. Amide nitrogen relaxation rates (R(1) and R(2)) and (1)H-(15)N NOE
      values were measured for RPA70A in the absence and presence of d-CTTCA. Analysis
      of the data using the Model-Free formalism and spectral density mapping
      approaches showed that the structural changes in the binding site are accompanied
      by some significant changes in flexibility of the primary DNA-binding loops on
      multiple timescales. On the basis of these results and comparisons to related
      proteins, we propose that the mechanism of sequence-nonspecific binding of ssDNA
      involves dynamic remodeling of the binding surface.

PMID- 12237455
TI  - The SPOT technique as a tool for studying protein tyrosine phosphatase substrate
      specificities.
AB  - The activity of protein tyrosine phosphatases (PTPs) is restricted by their
      substrate specificities. The analysis of PTP specificity was greatly helped by
      the discovery that "substrate-trapping" PTP mutants, such as PTP-1B D181A, stably
      and specifically bind their substrates. We have set up a PTP substrate
      specificity assay based on the SPOT technique, which involves the microsynthesis
      of (phospho)peptides on membranes. To validate this approach, substrate trapping
      PTP-1B was tested on its cognate ligand, the autophosphorylated insulin receptor
      (IR). On SPOT membranes, IR peptides with phosphotyrosine 1163 were efficiently
      bound by PTP1B D181A, and dephosphorylated by PTP-1B. Phosphotyrosine 1163 was
      preferred over the neighboring 1158 and 1162 phosphotyrosines. PTP-1B also
      recognized IR-like motifs in Trk autophosphorylation domains, and STAT 5
      phosphopeptides. Using a gridded 20-by-20 SPOT library, we show that peptides
      with the YZM motif (Z: phosphotyrosine) are the strongest ligands for PTP-1B
      D181A, but not the optimal substrates for dephosphorylation by wild-type PTP1B.
      In addition we show that PTP-1B and PTP-beta dephosphorylation efficiency is
      strongly modulated by the introduction of phospho-serine or phospho-threonine in
      their cognate phospho-tyrosine substrates. Altogether our data illustrate that
      the SPOT technique is a highly efficient tool for the study of PTP substrate
      specificity.

PMID- 12237456
TI  - Molecular dynamics simulations of alanine rich beta-sheet oligomers: Insight into
      amyloid formation.
AB  - The aggregation observed in protein conformational diseases is the outcome of
      significant new beta-sheet structure not present in the native state. Peptide
      model systems have been useful in studies of fibril aggregate formation.
      Experimentally, it was found that a short peptide AGAAAAGA is one of the most
      highly amyloidogenic peptides. This peptide corresponds to the Syrian hamster
      prion protein (ShPrP) residues 113-120. The peptide was observed to be conserved
      in all species for which the PrP sequence has been determined. We have simulated
      the stabilities of oligomeric AGAAAAGA and AAAAAAAA (A8) by molecular dynamic
      simulations. Oligomers of both AGAAAAGA and AAAAAAAA were found to be stable when
      the size is 6 to 8 (hexamer to octamer). Subsequent simulation of an additional
      alpha-helical AAAAAAAA placed on the A8-octamer surface has revealed molecular
      events related to conformational change and oligomer growth. Our study addresses
      both the minimal oligomeric size of an aggregate seed and the mechanism of seed
      growth. Our simulations of the prion-derived 8-residue amyloidogenic peptide and
      its variant have indicated that an octamer is stable enough to be a seed and that
      the driving force for stabilization is the hydrophobic effect.

PMID- 12237458
TI  - Topological investigation of amyloid fibrils obtained from beta2-microglobulin.
AB  - Amyloid fibrils of patients treated with regular hemodialysis essentially
      consists of beta2-microglobulin (beta2-m) and its truncated species DeltaN6beta2
      m lacking six residues at the amino terminus. The truncated fragment has a more
      flexible three-dimensional structure and constitutes an excellent candidate for
      the analysis of a protein in the amyloidogenic conformation. The surface topology
      of synthetic fibrils obtained from intact beta2-m and truncated DeltaN6beta2-m
      was investigated by the limited proteolysis/mass spectrometry approach that
      appeared particularly suited to gain insights into the structure of beta2-m
      within the fibrillar polymer. The distribution of prefential proteolytic sites
      observed in both fibrils revealed that the central region of the protein, which
      had been easily cleaved in the full-length globular beta2-m, was fully protected
      in the fibrillar form. In addition, the amino- and carboxy-terminal regions of
      beta2-m became exposed to the solvent in the fibrils, whereas they were masked
      completely in the native protein. These data indicate that beta2-m molecules in
      the fibrils consist of an unaccessible core comprising residues 20-87 with the
      strands I and VIII being not constrained in the fibrillar polymer and exposed to
      the proteases. Moreover, proteolytic cleavages observed in vitro at Lys 6 and Lys
      19 reproduce specific cleavages that have to occur in vivo to generate the
      truncated forms of beta2-m occurring in natural fibrils. On the basis of these
      data, a possible mechanism for fibril formation from native beta2-m is discussed
      and an explanation for the occurrence of truncated protein species in natural
      fibrils is given.

PMID- 12237457
TI  - The origins of asymmetry in the folding transition states of protein L and
      protein G.
AB  - Topology has been shown to be an important determinant of many features of
      protein folding; however, the delineation of sequence effects on folding remains
      obscure. Furthermore, differentiation between the two influences proves difficult
      due to their intimate relationship. To investigate the effect of sequence in the
      absence of significant topological differences, we examined the folding
      mechanisms of segment B1 peptostreptococcal protein L and segment B1 of
      streptococcal protein G. These proteins share the same highly symmetrical
      topology. Despite this symmetry, neither protein folds through a symmetrical
      transition state. We analyzed the origins of this difference using theoretical
      models. We found that the strength of the interactions present in the N-terminal
      hairpin of protein L causes this hairpin to form ahead of the C-terminal hairpin.
      The difference in chain entropy associated with the formation of the hairpins of
      protein G proves sufficient to beget initiation of folding at the shorter C
      terminal hairpin. Our findings suggest that the mechanism of folding may be
      understood by examination of the free energy associated with the formation of
      partially folded microstates.

PMID- 12237459
TI  - PrfA protein of Bacillus species: prediction and demonstration of endonuclease
      activity on DNA.
AB  - The prfA gene product of Gram-positive bacteria is unusual in being implicated in
      several cellular processes; cell wall synthesis, chromosome segregation, and DNA
      recombination and repair. However, no homology of PrfA with other proteins has
      been evident. Here we report a structural relationship between PrfA and the
      restriction enzyme PvuII, and thereby produce models that predict that PrfA binds
      DNA. Indeed, wild-type Bacillus stearothermophilus PrfA, but not a catalytic site
      mutant, nicked one strand of supercoiled plasmid templates leaving 5'-phosphate
      and 3'-hydroxyl termini. This activity, much lower on linear or relaxed circular
      double-stranded DNA or on single-stranded DNA, is consistent with a role for this
      protein in chromosome segregation, DNA recombination, or DNA repair.

PMID- 12237460
TI  - New insights into intracellular lipid binding proteins: The role of buried water.
AB  - The crystal structures of most intracellular lipid binding proteins (LBPs) show
      between 5 and 20 internally bound water molecules, depending on the presence or
      the absence of ligand inside the protein cavity. The structural and functional
      significance of these waters has been discussed for several LBPs based on studies
      that used various biophysical techniques. The present work focuses on two very
      different LBPs, heart-type fatty acid binding protein (H-FABP) and ileal lipid
      binding protein (ILBP). Using high-resolution nuclear magnetic resonance
      spectroscopy, certain resonances belonging to side-chain protons that are located
      inside the water-filled lipid binding cavity were observed. In the case of H
      FABP, the pH- and temperature-dependent behavior of selected side-chain
      resonances (Ser82 OgH and the imidazole ring protons of His93) indicated an
      unusually slow exchange with the solvent, implying that the intricate hydrogen
      bonding network of amino-acid side-chains and water molecules in the protein
      interior is very rigid. In addition, holo H-FABP appeared to display a reversible
      self-aggregation at physiological pH. For ILBP, on the other hand, a more solvent
      accessible protein cavity was deduced based on the pH titration behavior of its
      histidine residues. Comparison with data from other LBPs implies that the
      evolutionary specialization of LBPs for certain ligand types was not only because
      of mutations of residues directly involved in ligand binding but also to a
      refinement of the internal water scaffold.

PMID- 12237461
TI  - Drug resistance in HIV-1 protease: Flexibility-assisted mechanism of compensatory
      mutations.
AB  - The emergence of drug-resistant variants is a serious side effect associated with
      acquired immune deficiency syndrome therapies based on inhibition of human
      immunodeficiency virus type 1 protease (HIV-1 PR). In these variants,
      compensatory mutations, usually located far from the active site, are able to
      affect the enzymatic activity via molecular mechanisms that have been related to
      differences in the conformational flexibility, although the detailed mechanistic
      aspects have not been clarified so far. Here, we perform multinanosecond
      molecular dynamics simulations on L63P HIV-1 PR, corresponding to the wild type,
      and one of its most frequently occurring compensatory mutations, M46I, complexed
      with the substrate and an enzymatic intermediate. The quality of the calculations
      is established by comparison with the available nuclear magnetic resonance data.
      Our calculations indicate that the dynamical fluctuations of the mutated enzyme
      differ from those in the wild type. These differences in the dynamic properties
      of the adducts with the substrate and with the gem-diol intermediate might be
      directly related to variations in the enzymatic activity and therefore offer an
      explanation of the observed changes in catalytic rate between wild type and
      mutated enzyme. We anticipate that this "flexibility-assisted" mechanism might be
      effective in the vast majority of compensatory mutations, which do not change the
      electrostatic properties of the enzyme.

PMID- 12237462
TI  - Molecular modeling-based analysis of interactions in the RFC-dependent clamp
      loading process.
AB  - Replication and related processes in eukaryotic cells require replication factor
      C (RFC) to load a molecular clamp for DNA polymerase in an ATP-driven process,
      involving multiple molecular interactions. The detailed understanding of this
      mechanism is hindered by the lack of data regarding structure, mutual
      arrangement, and dynamics of the players involved. In this study, we analyzed
      interactions that take place during loading onto DNA of either the PCNA clamp or
      the Rad9-Rad1-Hus1 checkpoint complex, using computationally derived molecular
      models. Combining the modeled structures for each RFC subunit with known
      structural, biochemical, and genetic data, we propose detailed models of how two
      of the RFC subunits, RFC1 and RFC3, interact with the C-terminal regions of PCNA.
      RFC1 is predicted to bind PCNA similarly to the p21-PCNA interaction, while the
      RFC3-PCNA binding is proposed to be similar to the E. coli delta-beta
      interaction. Additional sequence and structure analysis, supported by
      experimental data, suggests that RFC5 might be the third clamp loader subunit to
      bind the equivalent PCNA region. We discuss functional implications stemming from
      the proposed model of the RFC1-PCNA interaction and compare putative clamp
      interacting regions in RFC1 and its paralogs, Rad17 and Ctf18. Based on the
      individual intermolecular interactions, we propose RFC and PCNA arrangement that
      places three RFC subunits in association with each of the three C-terminal
      regions in PCNA. The two other RFC subunits are positioned at the two PCNA
      interfaces, with the third PCNA interface left unobstructed. In addition, we map
      interactions at the level of individual subunits between the alternative clamp
      loader/clamp system, Rad17-RFC(2-5)/Rad9-Rad1-Hus1. The proposed models of
      interaction between two clamp/clamp loader pairs provide both structural
      framework for interpretation of existing experimental data and a number of
      specific findings that can be subjected to direct experimental testing.

PMID- 12237463
TI  - A kinetic study of beta-lactoglobulin amyloid fibril formation promoted by urea.
AB  - The formation of fibrillar aggregates by beta-lactoglobulin in the presence of
      urea has been monitored by using thioflavin T fluorescence and transmission
      electron microscopy (TEM). Large quantities of aggregated protein were formed by
      incubating beta-lactoglobulin in 3-5 M urea at 37 degrees C and pH 7.0 for 10-30
      days. The TEM images of the aggregates in 3-5 M urea show the presence of fibrils
      with diameters of 8-10 nm, and increases in thioflavin T fluorescence are
      indicative of the formation of amyloid structures. The kinetics of spontaneous
      fibrillogenesis detected by thioflavin T fluorescence show sigmoidal behavior
      involving a clear lag phase. Moreover, addition of preformed fibrils into protein
      solutions containing urea shows that fibril formation can be accelerated by
      seeding processes that remove the lag phase. Both of these findings are
      indicative of nucleation-dependent fibril formation. The urea concentration where
      fibril formation is most rapid, both for seeded and unseeded solutions, is
      approximately 5.0 M, close to the concentration of urea corresponding to the
      midpoint of unfolding (5.3 M). This result indicates that efficient fibril
      formation involves a balance between the requirement of a significant population
      of unfolded or partially unfolded molecules and the need to avoid conditions that
      strongly destabilize intermolecular interactions.

PMID- 12237464
TI  - Site-specific DNA cleavage of synthetic NarL sites by an engineered Escherichia
      coli NarL protein-1,10-phenanthroline cleaving agent.
AB  - The NarL response regulatory protein of Escherichia coli has been engineered by
      covalent modification with 1,10-phenanthroline (OP) to create a set of site
      specific DNA-cleaving agents. This was accomplished by introducing single
      cysteine amino acid replacements at selected locations within the carboxy
      terminal DNA-binding domain in or nearby the helix 8 to helix 9 region of the
      NarL protein using site-directed mutagenesis. Of 18 modified NarL-OP proteins
      made, 13 retained the ability to bind DNA as evidenced by gel mobility assays,
      whereas 10 of the 1,10-phenanthroline-modified proteins also exhibited specific
      cleavage activity for a synthetic NarL recognition sequence. These DNA-cleaving
      agents were divided into two groups based on the location of the cleavage sites.
      The first class set cleaved the DNA nearby the center of a synthetic 7-2-7
      sequence composed of two NarL heptamer sites separated by a 2-bp spacer element.
      The second class cut the DNA at the periphery of the 7-2-7 sequence. The cleavage
      data are consistent with the ability of two NarL monomers to recognize and bind
      to the DNA in a head-to-head orientation. A second set of DNA-cleaving agents was
      constructed using the carboxy-terminal domain of NarL called NarL(C). Similar
      cleavage patterns were observed whether full-length NarL or NarL(C) was used. The
      availability of 1,10-phenanthroline-modified NarL and NarL(C) proteins opens up
      the possibility to explore the position, orientation, and number of NarL
      recognition sites at E. coli promoters predicted to contain multiple and complex
      arrangements of NarL-binding sites.

PMID- 12237465
TI  - A simple model for polyproline II structure in unfolded states of alanine-based
      peptides.
AB  - The striking similarity between observed circular dichroism spectra of nonprolyl
      homopolymers and that of regular left-handed polyproline II (P(II)) helices
      prompted Tiffany and Krimm to propose in 1968 that unordered peptides and
      unfolded proteins are built of P(II) segments linked by sharp bends. A large body
      of experimental evidence, accumulated over the past three decades, provides
      compelling evidence in support of the original hypothesis of Tiffany and Krimm.
      Of particular interest are the recent experiments of Shi et al. who find
      significant P(II) structure in a short unfolded alanine-based peptide. What is
      the physical basis for P(II) helices in peptide and protein unfolded states? The
      widely accepted view is that favorable chain-solvent hydrogen bonds lead to a
      preference for dynamical fluctuations about noncooperative P(II) helices in
      water. Is this preference simply a consequence of hydrogen bonding or is it a
      manifestation of a more general trend for unfolded states which are appropriately
      viewed as chains in a good solvent? The prevalence of closely packed interiors in
      folded proteins suggests that under conditions that favor folding, water-which is
      a better solvent for itself than for any polypeptide chain-expels the chain from
      its midst, thereby maximizing chain packing. Implicit in this view is a
      complementary idea: under conditions that favor unfolding, chain-solvent
      interactions are preferred and in a so-called good solvent, chain packing density
      is minimized. In this work we show that minimization of chain packing density
      leads to preferred fluctuations for short polyalanyl chains around canonical,
      noncooperative P(II)-like conformations. Minimization of chain packing is modeled
      using a purely repulsive soft-core potential between polypeptide atoms. Details
      of chain-solvent interactions are ignored. Remarkably, the simple model captures
      the essential physics behind the preference of short unfolded alanine-based
      peptides for P(II) helices. Our results are based on a detailed analysis of the
      potential energy landscape which determines the system's structural and
      thermodynamic preferences. We use the inherent structure formalism of Stillinger
      and Weber, according to which the energy landscape is partitioned into basins of
      attraction around local minima. We find that the landscape for the experimentally
      studied seven-residue alanine-based peptide is dominated by fluctuations about
      two noncooperative structures: the left-handed polyproline II helix and its
      symmetry mate.

PMID- 12237466
TI  - Crystal structure of the ADP-dependent glucokinase from Pyrococcus horikoshii at
      2.0-A resolution: a large conformational change in ADP-dependent glucokinase.
AB  - Although ATP is the most common phosphoryl group donor for kinases, some kinases
      from certain hyperthermophilic archaea such as Pyrococcus horikoshii and
      Thermococcus litoralis use ADP as the phosphoryl donor. Those are ADP-dependent
      glucokinases (ADPGK) and phosphofructokinases in their glycolytic pathway. Here,
      we succeeded in gene cloning the ADPGK from P. horikoshii OT3 (phGK) in
      Escherichia coli,and in easy preparation of the enzyme, crystallization, and the
      structure determination of the apo enzyme. Recently, the three-dimensional
      structure of the ADPGK from T. litoralis (tlGK) in a complex with ADP was
      reported. The overall structure of two homologous enzymes (56.7%) was basically
      similar: This means that they consisted of large alpha/beta-domains and small
      domains. However, a marked adjustment of the two domains, which is a 10-A
      translation and a 20 degrees rotation from the conserved GG sequence located at
      the center of the hinge, was observed between the apo-phGK and ADP-tlGK
      structures. The ADP-binding loop (430-439) was disordered in the apo form. It is
      suggested that a large conformational change takes place during the enzymatic
      reaction.

PMID- 12237468
TI  - A structure for the yeast prohibitin complex: Structure prediction and evidence
      from chemical crosslinking and mass spectrometry.
AB  - The mitochondrial prohibitin complex consists of two subunits (PHB1 of 32 kD and
      PHB2 of 34 kD), assembled into a membrane-associated supercomplex of
      approximately 1 MD. A chaperone-like function in holding and assembling newly
      synthesized mitochondrial polypeptide chains has been proposed. To further
      elucidate the function of this complex, structural information is necessary. In
      this study we use chemical crosslinking, connecting lysine side chains, which are
      well scattered along the sequence. Crosslinked peptides from protease digested
      prohibitin complexes were identified with mass spectrometry. From these results,
      spatial restraints for possible protein conformation were obtained. Many
      interaction sites between PHB1 and PHB2 were found, whereas no homodimeric
      interactions were observed. Secondary and tertiary structural predictions were
      made using several algorithms and the models best fitting the spatial restraints
      were selected for further evaluation. From the structure predictions and the
      crosslink data we derived a structural building block of one PHB1 and one PHB2
      subunit, strongly intertwined along most of their length. The size of the complex
      implies that approximately 14 of these building blocks are present. Each unit
      contains a putative transmembrane helix in PHB2. Taken together with the unit
      building block we postulate a circular palisade-like arrangement of the building
      blocks projecting into the intermembrane space.

PMID- 12237467
TI  - Zinc-substituted Desulfovibrio gigas desulforedoxins: resolving subunit
      degeneracy with nonsymmetric pseudocontact shifts.
AB  - Desulfovibrio gigas desulforedoxin (Dx) consists of two identical peptides, each
      containing one [Fe-4S] center per monomer. Variants with different iron and zinc
      metal compositions arise when desulforedoxin is produced recombinantly from
      Escherichia coli. The three forms of the protein, the two homodimers
      [Fe(III)/Fe(III)]Dx and [Zn(II)/Zn(II)]Dx, and the heterodimer
      [Fe(III)/Zn(II)]Dx, can be separated by ion exchange chromatography on the basis
      of their charge differences. Once separated, the desulforedoxins containing iron
      can be reduced with added dithionite. For NMR studies, different protein samples
      were prepared labeled with (15)N or (15)N + (13)C. Spectral assignments were
      determined for [Fe(II)/Fe(II)]Dx and [Fe(II)/Zn(II)]Dx from 3D (15)N TOCSY-HSQC
      and NOESY-HSQC data, and compared with those reported previously for
      [Zn(II)/Zn(II)]Dx. Assignments for the (13)C(alpha) shifts were obtained from an
      HNCA experiment. Comparison of (1)H-(15)N HSQC spectra of [Zn(II)/Zn(II)]Dx,
      [Fe(II)/Fe(II)]Dx and [Fe(II)/Zn(II)]Dx revealed that the pseudocontact shifts in
      [Fe(II)/Zn(II)]Dx can be decomposed into inter- and intramonomer components,
      which, when summed, accurately predict the observed pseudocontact shifts observed
      for [Fe(II)/Fe(II)]Dx. The degree of linearity observed in the pseudocontact
      shifts for residues >/=8.5 A from the metal center indicates that the replacement
      of Fe(II) by Zn(II) produces little or no change in the structure of Dx. The
      results suggest a general strategy for the analysis of NMR spectra of homo
      oligomeric proteins in which a paramagnetic center introduced into a single
      subunit is used to break the magnetic symmetry and make it possible to obtain
      distance constraints (both pseudocontact and NOE) between subunits.

PMID- 12237469
TI  - Structure and dynamics of copper-free SOD: The protein before binding copper.
AB  - The solution structure of the copper-free state of a monomeric form of superoxide
      dismutase (153 amino acids) was determined through (13)C and (15)N labeling. The
      protein contained two mutations at the native subunit-subunit interface (F50E and
      G51E) to obtain a soluble monomeric species and a mutation in the active site
      channel (E133Q). About 93% of carbon atoms, 95% of nitrogen atoms, and 96% of the
      protons were assigned. A total of 2467 meaningful NOEs and 170 dihedral angles
      provided a family of 35 conformers with RMSD values of 0.76 +/- 0.09 A for the
      backbone and 1.22 +/- 0.13 A for all heavy atoms. The secondary structure
      elements, connected by loops, produce the typical superoxide dismutase Greek key
      fold, formed by an eight-stranded beta-barrel. The comparison with the copper
      bound monomeric and dimeric structures shows that the metal ligands have a
      conformation very close to that of the copper-bound forms. This feature indicates
      that the copper-binding site is preorganized and well ordered also in the absence
      of the copper ion. The active-site channel shows a sizable increase in width,
      achieving a suitable conformation to receive the copper ion. The histidines ring
      NH resonances that bind the copper ion and the region around the active-site
      channel experience, as found from (15)N relaxation studies, conformational
      exchange processes. The increased width of the channel and the higher mobility of
      the histidine rings of the copper site in the copper-free form with respect to
      the holoprotein is discussed in terms of the process of copper insertion.

PMID- 12237471
TI  - The kinetics of G-CSF folding.
AB  - The folding kinetics of G-CSF were determined by trp-fluorescence and far-UV
      circular dichroism. Folding and unfolding was achieved by rapid dilution and
      mixing of the denaturant, GdnHCl. G-CSF is a four-helical bundle protein with two
      long loops between the first and second helices and between the third and fourth
      helices. The entire conformational change expected by fluorescence was observed
      by stopped-flow technology, but due to rapid refolding kinetics only a portion
      was observed by circular dichroism. G-CSF contains two trp residues, and their
      contribution to the fluorescent-detected kinetics were deciphered through the use
      of single-site trp mutants. The trp moieties are probes of the local conformation
      surrounding their environment. One trp at residue 118 is located within the third
      helix while the other trp at residue 58 is part of the long loop between the
      first and second helices. The refolding results were most consistent with the
      following mechanism: U <--> I(1) <--> I(2) <--> N; where U represents the
      unfolded protein, I(1) represents intermediate state 1, I(2) represents
      intermediate state 2, and N represents the native state. I(1) is characterized as
      having approximately one-half of the native-like helical structure and none of
      the native-like fluorescence. I(2) has 100% of the native helical structure and
      most of the trp-118 and little of the trp-58 native-like fluorescence. Thus
      refolding occurs in distinct stages with half of the helix forming first followed
      by the remaining half of the helix including the third helix and finally the loop
      between the first and second helices folds.

PMID- 12237470
TI  - Mapping and characterization of the functional epitopes of tissue inhibitor of
      metalloproteinases (TIMP)-3 using TIMP-1 as the scaffold: a new frontier in TIMP
      engineering.
AB  - Tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE/ADAM-17) is
      responsible for the release of TNF-alpha, a potent proinflammatory cytokine
      associated with many chronic debilitating diseases such as rheumatoid arthritis.
      Among the four variants of mammalian tissue inhibitor of metalloproteinases (TIMP
      1 to -4), TACE is specifically inhibited by TIMP-3. We set out to delineate the
      basis for this specificity by examining the solvent accessibility of every
      epitope on the surface of a model of the truncated N-terminal domain form of TIMP
      3 (N-TIMP-3) in a hypothetical complex with the crystal structure of TACE. The
      epitopes suspected of interacting with TACE were systematically transplanted onto
      N-TIMP-1. We succeeded in transforming N-TIMP-1 into an active inhibitor for TACE
      (K(i)(app) 15 nM) with the incorporation of Ser4, Leu67, Arg84, and the TIMP-3 AB
      loop. The combined effects of these epitopes are additive. Unexpectedly,
      introduction of "super-N-TIMP-3" epitopes, defined in our previous work, only
      impaired the affinity of N-TIMP-1 for TACE. Our mutagenesis results indicate that
      TIMP-3-TACE interaction is a delicate process that requires highly refined
      surface topography and flexibility from both parties. Most importantly, our
      findings confirm that the individual characteristics of TIMP could be
      transplanted from one variant to another.

PMID- 12237473
TI  - Changing the net charge from negative to positive makes ribonuclease Sa
      cytotoxic.
AB  - Ribonuclease Sa (pI = 3.5) from Streptomyces aureofaciens and its 3K (D1K, D17K,
      E41K) (pI = 6.4) and 5K (3K + D25K, E74K) (pI = 10.2) mutants were tested for
      cytotoxicity. The 5K mutant was cytotoxic to normal and v-ras-transformed NIH3T3
      mouse fibroblasts, but RNase Sa and 3K were not. The structure, stability, and
      activity of the three proteins are comparable, but the net charge at pH 7
      increases from -7 for RNase Sa to -1 for 3K and to +3 for 5K. These results
      suggest that a net positive charge is a key determinant of ribonuclease
      cytotoxicity. The cytotoxic 5K mutant preferentially attacks v-ras-NIH3T3
      fibroblasts, suggesting that mammalian cells expressing the ras-oncogene are
      potential targets for ribonuclease-based drugs.

PMID- 12237472
TI  - Bacterial expression and membrane targeting of the rat complement regulator Crry:
      a new model anticomplement therapeutic.
AB  - Inappropriate or unregulated activation of complement can contribute to pathology
      in inflammatory diseases. Previous studies have shown that soluble recombinant
      regulators of complement are effective in animal models and some human diseases.
      However, limitations include cost, rapid clearance, and unwanted systemic
      effects. To avoid some of these problems, bacterial expression of regulators has
      been optimized and methods for the addition of a membrane-targeting moiety to the
      complement regulator developed. When administered directly to sites of
      inflammation, membrane-targeted human regulators are retained and inhibit
      complement-activation locally. To test the efficacy of membrane-targeted
      complement regulators in vivo, we have undertaken the expression and membrane
      targeting of the rat-complement regulator Crry. A soluble recombinant form of
      Crry, containing only the first four short consensus repeats, was expressed in a
      mammalian expression system and shown to be functional as a fluid phase
      regulator. To generate the quantities required for testing in vivo, Crry was
      expressed in bacteria and refolded successfully. Refolded protein had full
      complement regulatory activity in vitro. Attachment of a membrane address tag
      conferred membrane-binding capacity and greatly increased complement regulatory
      function in vitro. This novel anticomplement agent can now be applied to rat
      models of arthritis and other inflammatory diseases.

PMID- 12237474
TI  - Cannabinoid receptor-G protein interactions: G(alphai1)-bound structures of IC3
      and a mutant with altered G protein specificity.
AB  - The structure of the C-terminal region of the third cytoplasmic loop (IC3) of the
      cannabinoid receptor one (CB1) bound to G(alphai1) has been determined using
      transferred nuclear Overhauser effects (NOEs). The wild-type IC3 sequence is
      helical when associated with G(alphai1). In contrast, a peptide containing the
      amino-acid inversion, Ala(341)-Leu(342) adopts a single turn. These findings
      correlate with the attenuated G(i) association of CB1 with the Ala(341)-Leu(342)
      mutation previously observed in vivo and the diminished stimulation of G(alphai1)
      GTPase activity by the corresponding peptide demonstrated in vitro here. These
      results, the first to report the structure of a GPCR domain while associated with
      G protein, imply the C-terminus of CB1 IC3, a region with high-sequence
      conservation among G-protein coupled receptors, must be helical for efficient
      coupling and activation of the G(i) protein.

PMID- 12237475
TI  - Akt induces enhanced myocardial contractility and cell size in vivo in transgenic
      mice.
AB  - The serine-threonine kinase Akt seems to be central in mediating stimuli from
      different classes of receptors. In fact, both IGF-1 and IL6-like cytokines induce
      hypertrophic and antiapoptotic signals in cardiomyocytes through PI3K-dependent
      Akt activation. More recently, it was shown that Akt is involved also in the
      hypertrophic and antiapoptotic effects of beta-adrenergic stimulation. Thus, to
      determine the effects of Akt on cardiac function in vivo, we generated a model of
      cardiac-specific Akt overexpression in mice. Transgenic mice were generated by
      using the E40K, constitutively active mutant of Akt linked to the rat alpha
      myosin heavy chain promoter. The effects of cardiac-selective Akt overexpression
      were studied by echocardiography, cardiac catheterization, histological and
      biochemical techniques. We found that Akt overexpression produced cardiac
      hypertrophy at the molecular and histological levels, with a significant increase
      in cardiomyocyte cell size and concentric LV hypertrophy. Akt-transgenic mice
      also showed a remarkable increase in cardiac contractility compared with wild
      type controls as demonstrated by the analysis of left ventricular (dP/dt(max)) in
      an invasive hemodynamic study, although with graded dobutamine infusion, the
      maximum response was not different from that in controls. Diastolic function,
      evaluated by left ventricular dP/dt(min), was not affected at rest but was
      impaired during graded dobutamine infusion. Isoproterenol-induced cAMP levels,
      beta-adrenergic receptor (beta-AR) density, and beta-AR affinity were not altered
      compared with control mice. Moreover, studies on signaling pathway activation
      from myocardial extracts demonstrated that glycogen synthase kinase3-beta is
      phosphorylated, whereas p42/44 mitogen-activated protein kinases is not,
      indicating that Akt induces hypertrophy in vivo by activating the glycogen
      synthase kinase3-beta/GATA 4 pathway. In summary, our results not only
      demonstrate that Akt regulates cardiomyocyte cell size in vivo, but, importantly,
      show that Akt modulates cardiac contractility in vivo without directly affecting
      beta-AR signaling capacity.

PMID- 12237476
TI  - Prevalence of tetanus immunity in the Egyptian population.
AB  - Our aim was to determine the level of tetanus immunity in the general Egyptian
      population. The surveyed population consisted of 709 healthy subjects from five
      regions of Egypt, 2 month to 105 years of age. We used an ELISA assay to
      determine titers of anti-tetanus IgG. According to the widely used criteria,
      31.7% was susceptible to tetanus (IgG level < 0.15 IU/ml), 15.7% protection (0.15
      1.0 IU/ml), and 52.6% > or = 1.0 IU/ml). The results revealed that the majority
      (68.3%) population from 2 months to 50 years had a protective level of IgG
      against tetanus. The level of susceptibility increases with age until it reaches
      90.3% Significantly, more males (23.7%) unprotected against tetanus. Our results
      suggest that monitoring immunization status and administering the tetanus vaccine
      as required are essential to insure adequate and long-lasting antibody levels.

PMID- 12237477
TI  - Acute effects of glibenclamide on reactive hyperaemia in the lower limbs in
      humans.
AB  - Three episodes of 1 min ischemia in the lower limbs in humans reduced the
      metabolic debt repayment (expressed as AUC of reactive hyperaemia) following more
      prolonged ischemia (666.6+/-86.6 vs 500.0+/-33.5 ml/100 ml). The administration
      of the ATP-dependent K(+) channel blocker glibenclamide was associated with a
      significant reduction in the AUC of reactive hyperaemia (666.6+/-86.6 vs 563.1+/
      76.6 ml/100 ml), and with the removal of the protective effect produced by 3
      episodes of 1 min ischemia (563.1+/-76.6 vs 551.8+/-71.3 ml/100 ml). Plasma level
      of glibenclamide reached the peak value of 1.295+/-0.15 micromol/l 2 h after drug
      administration, ranging around the 1 micromol/l concentration in the following 3
      hours. Our findings produce indirect evidence that, similarly to the ischemic
      preconditioning of the heart, the protective effects towards ischemia of brief
      repeated episodes of sub-maximal occlusion in the peripheral circulation of the
      lower limbs in humans are mediated by ATP-dependent K(+) channels.

PMID- 12237478
TI  - Polymorphonuclear leukocyte integrin profile in diabetes mellitus.
AB  - We examined the polymorphonuclear leukocyte (PMN) integrin pattern in 45 diabetic
      subjects without macrovascular complications, including 21 subjects with type 1
      and 24 with type 2 diabetes mellitus. The PMN adhesion molecules (CD11a, CD11b,
      CD11c, CD18) were evaluated using indirect immunofluorescence and a flow
      cytometer, at baseline and after in vitro activation with 4-phorbol 12-myristate
      13-acetate (PMA) and N-formyl-methionyl-leucyl-phenyl-alanine (fMLP). At
      baseline, in diabetic subjects the phenotypical expression of CD11a and CD11b was
      significantly reduced and CD11c was increased, whereas CD18 was unchanged in
      comparison with normals. Considering type 1 and 2 diabetic subjects separately,
      CD11a was reduced and CD11c was increased in both subgroups, CD11b was decreased
      only in type 1 diabetics and CD18, decreased in type 1, was increased in type 2
      subjects. After activation with PMA and fMLP, in normal subjects we observed a
      significant increase of all PMN adhesion molecules whereas in diabetic subjects
      only CD11c increased significantly with both activating agents, and CD11b
      increased only after PMA activation. In type 1 diabetic subjects only CD11c
      expression was increased, and in type 2 diabetic subjects an increase of CD11b
      (with PMA) and an increase of CD11c (with fMLP) were noted. In conclusion, we
      found in diabetic subjects of type 1 and 2 an altered behaviour pattern of PMN
      integrins both at baseline and, in particular, after in vitro activation. These
      data may help in explaining the role of PMN in the evolution of diabetic vascular
      complications.

PMID- 12237479
TI  - Digital blood flow analysis from microscopic images of mesenteric microvessel
      with multiple branching.
AB  - Blood flow through frog mesenteric microvessel with multiple branching, at
      Reynolds number 0.022, is analyzed. After pre-processing the images the velocity
      and erythrocyte distribution profiles by image velocimetry and axial tomography
      are obtained, respectively. The vascular parameters and shape descriptors are
      obtained by image processing techniques. The axial velocity shows the variation
      around branching areas associated with an increase in radial velocity, which is
      up to 10% of axial velocity. From the erythrocyte distribution profiles at
      various locations in the microvessel the tomograms are reconstructed. Based on
      these the contours of equal concentration are reconstructed. From these contours
      the point-to-point variation in cell concentration throughout the microvessel is
      observed and regions where the cellular concentration varies from 3 to 5%, at
      zero axial velocity, are identified. The change in erythrocyte shape, determined
      by the shape descriptors, while passing through the capillary is significant.
      This passage of cells, depending on their orientation, also displaces the
      capillary walls by 1.5 to 2.5 microm.

PMID- 12237480
TI  - Plasma viscosity in female patients with hypothyroidism: effects of oxidative
      stress and cholesterol.
AB  - Hypothyroidism is associated with atherosclerotic events, however, the mechanism
      is unclear. We investigated the effects of oxidative stress and cholesterol on
      plasma viscosity in female patients with hypothyroidism (n = 20; mean age: 45.5
      +/- 5.5 years) at baseline and after L-thyroxine replacement therapy (average
      daily dose being 0.1 to 0.15 mg). Two blood samples were taken after 2.3 +/- 1.2
      months. In hypothyroid state plasma viscosity and thiobarbituric acid reactive
      substance (TBARS; marker of oxidative stress were significantly higher (p < 0.001
      and p < 0.001), and plasma protein thiol (antioxidants) levels were significantly
      lower (p < 0.001) than in the healthy state (female; n = 15). After L-thyroxine
      replacement therapy, patients reached to euthyroid state. In this state, the
      levels of plasma viscosity and TBARS were decreased (p < 0.001 and p < 0.001),
      and protein thiol levels were significantly elevated (p < 0.001). There was a
      significant correlation between plasma cholesterol and viscosity (r = 0.64, p <
      0.001), as well as plasma protein thiol (r = -0.59, p < 0.001) in the patients.
      The correlation between viscosity and TBARS was weak (r = 0.29, p < 0.01).
      Therefore hypothyroidism may be associated with atherosclerotic process by
      different mechanisms.

PMID- 12237481
TI  - Exercise-induced central retinal vein thrombosis: possible involvement of
      hemorheological disturbances. A case report.
AB  - Exercise-induced impairment in blood fluidity has been supposed to increase
      cardiovascular risk but there is no data to support this hypothesis. We report
      the case of a 50 yr old marathon runner who underwent a central retinal vein
      thrombosis after a marathon run. We investigated his rheological response to
      exercise compared to control subjects of previous studies. During a standardized
      sub-maximal exercise-test, the increase in blood viscosity (+28%) and hematocrit
      (+25%) exceeded the control range but the most striking differences were found
      for red cell aggregation (Myrenne +47%) and disaggregation thresholds (Affibio
      +37%). Although some of this post-exercise hyperviscosity pattern may be due to
      the previous vascular event, these findings may also support the hypothesis of a
      role for hemorheological alterations during exercise in the pathogenesis of this
      marathon-induced retinal thrombosis, and indicate that after such an event
      hemorheological adaptation to exercise remains markedly disturbed.

PMID- 12237482
TI  - Effect of high power ultrasound on endothelial cells--an in vitro study of the
      endothelium--hemostasis interaction.
AB  - OBJECTIVE: The goal of this study was to develop an in vitro model system in
      which the hemostatic effects of high power ultrasound applied to the outer
      surface of blood vessels during tumor dissection can be simulated and measured.
      METHODS: Monolayers of endothelial cells (HUVEC, ATCC) in cell culture plates
      were sonicated with an ultrasound dissector (SONOCA II, Soering) at a frequency
      of 23.5 kHz. The dissector was equipped with a cooling circuit. The cell cultures
      were exposed to 2 minutes of continuous ultrasound with intensities of 10, 50, or
      100 W/cm(2). To differentiate between heat and sound effects, selected monolayers
      were warmed for 2 minutes. Finally, the cell cultures were stained with trypan
      blue to assess for cell death due to membrane disruption. Cytomorphological
      alterations and changes in the concentration of coagulation parameters in the
      cell culture medium were evaluated. RESULTS: The cytomorphological alterations
      were found to depend on ultrasound intensity. They included detachment of single
      endothelial cells, cell cluster formation and cytoplasmic cavitation. Disruption
      of the cell membrane integrity was infrequently observed. Of 14 screened
      coagulation parameters, thromboxane B(2) (TXB(2)), prostaglandin F(1alpha)
      (PGF(1alpha)), plasminogen activator inhibitor type 1 (PAI-1), thrombomodulin
      (TM), and thrombospondin (TSP) were found to be ultrasound sensitive. TXB(2)
      concentrations in the medium increased beginning at low ultrasound intensities (p
      < 0.01) and were independent of temperature. PGF(1alpha) concentrations peaked at
      high ultrasound intensities (p < 0.05), and heat alone produced a significant
      increase in concentration (p < 0.05). At high intensities, the ratio of TXB(2) to
      PGF(1alpha) shifted in favour of PGF(1alpha). PAI-1 was most strongly secreted at
      low ultrasound intensities (p < 0.01), and heat resulted in a decrease of
      concentration (p < 0.05). TM and TSP concentrations correlated strongly and
      reached a non significant peak at low intensities. CONCLUSION: The results
      demonstrate that during sonication of endothelial cells in vitro, coagulation
      parameters are released from distant undamaged cells. HUVEC-cells exhibit a
      differential hemostaseological response at different ultrasound intensities, and
      the response is also influenced by heat. Additionally, massive morphological
      damage can be induced at the endothelium.

PMID- 12237484
TI  - Characteristics of light and heavy polymorphonuclear leukocytes.
AB  - Whole blood gravity sedimentation technique can be modified for studying
      leukocyte sedimentation properties. Previously, we demonstrated that the
      displacement rate of leukocytes was associated with activation of leukocytes
      during traditional gravity sedimentation of the whole blood. The plasma flow as
      well as the difference between the specific gravity of leukocytes and plasma
      propel the leukocytes upward in the sedimentation tube while the erythrocyte
      aggregates are descending. The leukocyte ascension rate can be described as the
      increment of leukocyte concentration in the upper half section of the blood
      column after one-hour sedimentation. The aim of the present study was to
      characterize the ascending and non-ascending leukocytes using a flow cytometric
      technique. Venous blood samples were taken from 8 healthy controls and 8 septic
      patients after major thoracic or abdominal surgical procedures. The upper and
      lower halves sections of venous blood column were separately removed from the
      sedimentation tube after one hour gravity sedimentation. Using flow cytometry,
      the leukocyte subsets were identified by their CD45 density and side scatter
      parameters followed by characterization of their cellular size and cytoplasmic
      granularity. The size indices of septic patients' ascending polymorphonuclear
      leukocytes (PMNs) were significantly lower than that of the non-ascending ones
      (253 +/- 22 versus 387 +/- 12 (SEM), p < 0.002) or the ascending PMN fraction
      taken from healthy individuals (382 +/- 28, p < 0.005). Septic patients'
      ascending PMNs presented significantly lower cytoplasmic granularity indices
      compared to non-ascending (447 +/- 23 versus 538 +/- 18, p < 0.05) or healthy
      ascending PMNs (539 +/- 20, p < 0.05). The cellular size and cytoplasmic
      granularity indices of heavy and light monocytes as well as lymphocytes were
      similar in both groups. It can be assumed that venous blood samples of septic
      patients contain significantly smaller PMNs with less cytoplasmic granularity
      than healthy control cells.

PMID- 12237483
TI  - Nitric oxide effects on human erythrocytes structural and functional properties-
      an in vitro study.
AB  - NO is present in the blood at 10(-7) M under physiological conditions, but at
      concentrations higher than 10(-6) M during inflammatory disease states. The aim
      of this study was to characterize what are the effects of these different NO
      concentrations on erythrocyte structural and functional properties. Blood was
      collected from eleven healthy men and incubated with SpermineNONOate in order to
      expose it during incubation time to NO concentrations between 10(-7) M and 10(-3)
      M. We measured erythrocyte aggregation and deformability, membrane lipid
      peroxidation and fluidity, p50, hemoglobin, oxyhemoglobin, methemoglobin
      concentrations and plasma pH, pO(2), pCO(2), Na(+), K(+) and Ca(2+). When blood
      was exposed to NO 10(-7) M erythrocyte deformability increase and p50 decrease.
      In presence of NO 10(-5) M lipid fluidity and p50 decrease. When blood was
      exposed to NO 10(-3) M methemoglobin concentration increase and erythrocyte
      deformability and p50 decrease but membrane fluidity and lipid peroxidation were
      similar to control. In conclusion, dependent of NO concentrations there is
      different effects on erythrocytes structural and functional properties.

PMID- 12237485
TI  - Viscoelastic and biochemical properties of erythrocytes during storage with SAG-M
      at +4 degrees C.
AB  - During storage at +4 degrees C, red blood cells undergo biochemical and
      physicochemical modifications, which alter their rheological characteristics
      especially the deformability. Even so until now not precisely defined
      deformability is undoubtedly a function of whole cell elasticity and viscosity.
      In a previous study we have investigated changes of elasticity of whole RBCs
      during a 6 weeks storage by quasi-static experiments using our Cell-Elastometer
      method. Since the changes in deformability we observed with that experimental
      approach have not been significant we extended the hard/software capabilities of
      this instrument to enable dynamic measurements also. We applied this modified
      hard-/software set-up to examine again changes in viscoelasticity of erythrocytes
      from concentrates during a six weeks storage at a blood bank. The cells were
      resuspended in CPD-SAG-M and stored at +4 degrees C. Quasi-static and dynamic
      experiments were performed on stored erythrocytes and showed for both significant
      changes in elasticity and viscoelasticity from the fourth week on. So it can be
      stated that due to our experimental results decrease in deformability of RBCs
      during storage occurs after a four weeks period of relative stability. To get
      further insight in changes of underlying or related biochemical properties
      according experiments have been performed in parallel. Especially the decrease in
      ATP showed a nearly parallel time course with a significant decrease after the
      4th week. All other parameters especially the 2,3 DPG level showed a nearly
      linear de- or increase with time which are in accordance with the results of the
      additionally performed elongation experiments. Our quasi-static and dynamic
      deformability measurements have been proven to provide a simple and reliable tool
      to follow up erythrocyte senescence during storage where a pronounced change in
      mechanical properties may be used as an indicator for a change in bioviability.
      This has to be verified in further experiments.

PMID- 12237486
TI  - Hemorheological investigations in patients with polycystic kidney disease.
AB  - Polycystic kidney disease (PKD) is associated with an increased incidence of
      hypertension and cardiovascular abnormalities. As hemorheology is an important
      hemodynamic determinant and may contribute to vasculopathies we measured whole
      blood viscosity and red blood cell (RBC) and plasma rheological factors in 38
      patients with PKD and compared this data with similar measurements in age- and
      sex-matched healthy controls. Renal function was assessed by plasma creatinine
      concentration. Analysis of the data showed that the PKD group had a significant
      reduction in mean hematocrit and an increase in mean plasma viscosity and mean
      plasma fibrinogen concentration. Intrinsic RBC rheology assessed by standardised
      viscosity measurements was impaired in patients with PKD compared to control
      subjects. The changes in plasma and RBC rheology did not however result in
      increased whole blood viscosity in the patients with PKD due to the reduction in
      hematocrit level. Correlation analyses demonstrated a significant relationship
      between increased plasma creatinine concentration and lower hematocrit, decreased
      whole blood viscosity and impaired RBC deformability but not with increased
      plasma viscosity or plasma fibrinogen concentration. This study shows that
      although PKD is associated with mild abnormalities in plasma rheology and
      intrinsic RBC rheology these changes are offset by a reduction in hematocrit. The
      changes in RBC rheological determinants in PKD appeared to be related to the
      degree of renal impairment.

PMID- 12237487
TI  - Erythrocyte deformability in survivors of acute myocardial infarction measured by
      two different methodologies.
AB  - In order to ascertain whether erythrocyte deformability (ED) is involved in
      chronic coronary syndromes, this rheological property was determined in 92
      survivors of acute myocardial infarction (AMI) who had had the acute event 3
      years ago and in 150 volunteers. From the 92 AMI survivors in 50 (43 males, 7
      females aged 61+/-9 years) ED was determined with filtrometric techniques (Hanss
      Hemorheometre) and in 42 (32 males, 10 females aged 63+/-11 years) with laser
      diffractometric ones (Rheodyn SSD). The control group consisted of 66 and 84
      volunteers whose ED was measured with the above mentioned devices respectively.
      Patients and controls were matched for age, sex, total cholesterol and
      triglyceride levels. With the Hanss Hemorheometre, the Rigidity Index (RI) was
      higher in patients than in controls (9.4+/-1.2 vs 8.7+/-1.5; p=0.01) although
      after adjusting for confounding variables (MCV and leukocyte count) in a logistic
      regression analysis the RI was no longer statistically significant. With the
      Rheodyn SSD the Erythrocyte Elongation Index (EEI) determined at 12, 30 and 60
      Pa, did not show statistically significant differences between cases and controls
      at any of the shear stresses tested. Our results suggest that AMI survivors who
      had had the ischemic event 3 years ago do not show decrease RBC deformability
      with either of the two methodologies used. Red blood cell deformability does not
      appear to contribute to impaired microcirculatory blood flow in chronic coronary
      syndromes.

PMID- 12237488
TI  - Towards a quantitative in vivo evaluation of venous blood echogenicity: image
      processing versus subjective assessment.
AB  - PURPOSE: Spontaneous blood echogenicity in vein ultrasound images may be a marker
      for an increased erythrocyte aggregability, but a reliable quantitative
      evaluation method is a prerequisite for its use in clinical studies. We compared
      a simple scoring system of blood echogenicity intensity and pattern, with
      automatic image analysis. MATERIAL AND METHODS: 157 femoral and popliteal vein
      digitized ultrasound sequences were reviewed by two independent observers who
      chose an image, delimited an area of interest (ROI), and graded blood
      echogenicity intensity and pattern, using a four class score. Each observer
      reviewed the images selected by the other, without and with ROI. The computer
      calculated first and second order parameters describing echo intensity and
      spatial organization. RESULTS: Inter-observer reproducibility of subjective
      assessment was poor (Kappa<0.5), whereas the automatically calculated ROI average
      gray level intensity relatively to the whole image (tau(1)) effectively separated
      all grades of intensity. No parameter effectively separated patterns. CONCLUSION:
      Tau(1) is a simple parameter for the in vivo evaluation of blood echogenicity
      intensity. It should be evaluated in standardized conditions for clinical
      hemorheology studies in correlation with in vitro erythrocyte aggregation
      measurements.

PMID- 12237489
TI  - Highlights of the 3rd Yaroslavl International Congress on Hemorheology, 29-31
      July 2001, Yaroslavl, Russia.

PMID- 12237490
TI  - Exposure of human neutrophils to oxygen radicals causes loss of deformability,
      lipid peroxidation, protein degradation, respiratory burst activation and loss of
      migration.
AB  - The effects of oxygen radical generating system of H(2)O(2) on neutrophil
      deformability, lipid peroxidation, protein degradation, chemotaxis, random
      migration and activation were studied in the presence and absence of selected
      anti-oxidants such as vitamin E and carbon monoxide. Hydrogen peroxide caused a
      significant loss of neutrophil deformability (measured as an index of
      filtration), loss of chemotaxis (using chemoattractant) and loss of random
      migration (spontaneous migration) under agarose gel. Hydrogen peroxide also
      caused a significant increase in lipid peroxidation (measured as
      malonyldialdehye) and protein degradation (measured as free alanine). Hydrogen
      peroxide also caused activation of neutrophils (measured by nitroblue tetrazolium
      dye test). Pre-incubation of neutrophils with vitamin E prevented significantly
      the increase in lipid peroxidation without affecting the loss of neutrophil
      deformability. However, pre-incubation with carbon monoxide prevented
      significantly the increase in protein degradation and the loss of neutrophil
      deformability. The results indicate the importance of oxidatively damaged cell
      proteins in compromising the rheologic behaviour and migration of neutrophils,
      particularly under oxidative stress conditions.

PMID- 12237491
TI  - The effect of long-term supplementation of vitamin C on leukocyte adhesion to the
      cerebral endothelium in STZ-induced diabetic rats.
AB  - The effect of long-term supplementation of vitamin C on leukocyte adhesion to the
      cerebral endothelium was investigated in streptozotocin (STZ)-induced diabetic
      rats. Diabetes was induced in male Wistar Furth rats by intravenous injection of
      STZ. The vitamin C, ascorbic acid, was supplemented with drinking water (1 g/l).
      The rats were divided into control and diabetic groups without or with
      supplementation of vitamin C. The cerebral microcirculation was directly observed
      through a cranial window after different periods (12, 24 and 36 weeks) of vitamin
      C supplementation, using fluorescence videomicroscopy. Leukocyte adhesion to the
      venular endothelium was examined by labeling leukocytes with rhodamin 6G. The
      number density of adherent leukocytes in STZ-diabetic rats was increased
      significantly, compared with control rats. This increase in leukocyte adhesion
      was prevented by the long-term supplemented vitamin C. It was suggested that the
      antioxidant effect of vitamin C might be responsible for the prevention of
      leukocyte adhesion in diabetes mellitus.

PMID- 12237492
TI  - Altered sensory input improves the accuracy of muscle reinnervation.
AB  - PURPOSE: To improve functional recovery after peripheral nerve suture, we
      characterized the quality of target reinnervation in rats in which the afferent
      trigeminal connection to facial motoneurons had been altered. METHODS: Employing
      an improved lesion model and a refined mode of retrograde tracer application, we
      studied the accuracy of reinnervation in rats which underwent buccal-buccal nerve
      anastomosis (BBA) alone (group 1), BBA plus excision of the ipsilateral
      infraorbital nerve (ION; group 2), and BBA plus excision of the contralateral ION
      (group 3). This was done by comparison between the number of double-labeled
      motoneurons after pre-operative injection of Fluoro-Gold (FG) and post-operative
      injection of Fast Blue (FB) into the whisker pad muscles. RESULTS: In the first
      group we counted 398 +/- 80 FG+FB double labeled cells (mean +/- SD; n = 9 rats),
      i.e., only 27% of all motoneurons that grew axons into the whisker pad had
      projected to these muscles before surgery. In group 2, this value was increased
      marginally to 436 +/- 68 (32%). In group 3,. we counted 580 +/- 63 double-labeled
      neurons. This is the first morphological report demonstrating significantly
      improved specificity of reinnervation. Indeed, 41% of the motoneurons innervating
      the target in group 3 belonged to the original neuron pool. These morphological
      findings are supported by evidence obtained from electrophysiological recordings
      and behavioural studies. CONCLUSIONS: The principle finding of the present study
      is that a peripheral lesion to the contralateral trigeminal nerve improves the
      quality of reinnervation of the whisker pad musculature by its original nerve.
      The contralateral trigeminal lesion may trigger behavioural demand and forced
      overuse of the axotomized facial nerve, which may be a key issue for recovery of
      vibrissae rhythmical whisking after facial nerve surgery.

PMID- 12237493
TI  - 5-lipoxygenase (5LOX)-deficient mice express reduced anxiety-like behavior.
AB  - PURPOSE: 5-Lipoxygenase (5LOX) is an enzyme critical for leukotriene synthesis
      from arachidonic acid. In addition to its role in peripheral inflammation, this
      enzyme is also expressed in the brain but its functional role in the central
      nervous system is poorly understood. An upregulated expression of brain 5LOX, for
      example during aging and in multiple sclerosis, has been associated with
      increased vulnerability to neurodegeneration. Moreover, the 5LOX pathway has been
      associated with the neurotoxicity of the prion peptide. 5LOX-deficient mice
      [5LOX(-); B6129S(Alox5tm1Fun)] and their controls (B6129SF2/J) have not been
      behaviorally characterized. METHODS: The following behavioral tests were used for
      behavioral characterization of 5LOX(-) mice: elevated plus-maze, marble burying,
      locomotor activity, rota-road, and the spontaneous alternations in T-maze.
      RESULTS: We found that in an elevated plus-maze, 5LOX(-) mice spent a shorter
      time in the "safe" closed arms, a longer time in the "anxiogenic" open arms, and
      entered the open arms more frequently. They also covered fewer marbles in the
      marble-burying anxiety test. No difference was observed between 5LOX(-) and
      5LOX(+) mice in other tests. CONCLUSION: These results indicate that 5LOX(-) mice
      are less prone to anxiety and point to a possible role for 5LOX in affective
      behaviors. We propose that creating congenic 5LOX(-) mice by backcrossing into
      inbred strains would provide additional tools to further elucidate this putative
      role.

PMID- 12237494
TI  - Brain activation pattern as assessed with multi-modal EEG analysis predict motor
      recovery among stroke patients with mild arm paresis who receive the Arm Ability
      Training.
AB  - PURPOSE: Receiving the Arm Ability Training for three weeks improves motor
      function among stroke patients with mild arm paresis. There is, however, a
      considerable variability in recovery among patients receiving the Arm Ability
      Training. The study investigated whether intersubject differences in movement
      related electric brain activity explain the variability in motor recovery.
      METHODS: In a sample of 9 patients receiving the Arm Ability Training both motor
      performance using a standardised arm function test (TEMPA) and movement-related
      electric brain activity, i.e. slow cortical potentials (DC) as well as event
      related desynchronisation of alpha (alpha-ERD) and beta activity (beta-ERD), were
      assessed before the Arm Ability Training was started. Stepwise multiple
      regression was used to establish the best predictive model for motor improvement
      scores (TEMPA difference from pre to post test three weeks later). RESULTS:
      Stepwise multiple regression indicated that electric brain activity during
      movement preparation explained the variance of motor improvement scores
      completely. Further, electric brain activity during movement as well as baseline
      motor performance accounted each for 50% of the variance of motor improvement
      scores. CONCLUSIONS: Activation of sensorimotor areas during movement preparation
      and deactivation of other cortical areas during movement execution seem to be
      factors that predict a favourable outcome after training.

PMID- 12237495
TI  - Do psychological variables modify motor recovery among patients with mild arm
      paresis after stroke or traumatic brain injury who receive the Arm Ability
      Training?
AB  - PURPOSE: The Arm Ability Training improves motor function among stroke and
      traumatic brain injury patients with mild arm paresis. There is, however, a
      considerable variability in motor recovery among patients receiving the Arm
      Ability Training. The study investigated whether psychological variables can
      explain the variability in motor recovery. METHODS: In a sample of 33 patients
      receiving the Arm Ability Training both motor performance (by use of the
      standardised arm function test TEMPA) and cognitive functions (attention,
      perceptual abilities, and learning) as well as depression were assessed before
      training was commenced. Both univariate correlational analyses and stepwise
      multiple regression were used to investigate these variables' ability to predict
      motor improvement (TEMPA difference scores from pre to post test after 3 weeks).
      RESULTS: The degree of motor dysfunction of the affected arm explained most (70%)
      of the variance of motor improvement scores of the standardised arm function test
      (TEMPA). Psychometric scores showed no or at the most weak associations with
      motor improvement (explaining at the most 10% of the variance). CONCLUSIONS:
      Psychological variables had not been critical modifiers of motor recovery among
      stroke and traumatic brain injury patients with mild arm paresis receiving the
      Arm Ability Training.

PMID- 12237496
TI  - The effects of Neotrofin on septodentate sprouting after unilateral entorhinal
      cortex lesions in rats.
AB  - PURPOSE: Recent research on the purine derivative of hypoxanthine Neotrofin (4
      [[3-(1,6-dihydro-6-oxo-9-purin-9-yl)-1-oxopropyl]amino]benzoic acid; AIT-082) has
      indicated that Neotrofin treatment elevates the mRNA levels of various
      neurotrophic factors, including nerve growth factor (NGF), in the CNS. Several
      previous studies have indicated that NGF may regulate septodentate sprouting
      after entorhinal cortex lesions in rats. Thus, the objective of this
      investigation was to determine whether Neotrofin treatment would enhance lesion
      induced septodentate sprouting from 4 to 15 days postlesion. METHODS: Sham
      operated rats or rats with EC lesions were injected (i.p.) with either Neotrofin
      (30 mg/kg) or saline (0.9%) immediately after surgery and every day thereafter
      until the end of the treatment regimen. Septodentate sprouting, as indicated by
      intensity of acetylcholinesterase (AChE) label in the dentate gyrus, was assessed
      with optical densitometry. RESULTS: We observed that Neotrofin elevated the AChE
      label in the outer molecular layer of the ventral dentate gyrus at 4 days
      postlesion and of the dorsal dentate gyrus at 15 days postlesion. CONCLUSIONS:
      Neotrofin appears to have exerted limited stimulatory effects on lesion-induced
      sprouting by a cholinergic pathway.

PMID- 12237497
TI  - Return to work after spinal cord injury: a review of recent research.
AB  - This manuscript reviews recent research on return to work (RTW) for individuals
      who sustain spinal cord injury (SCI), including the effects of demographics
      variables, occupational characteristics, workplace accommodations, quality of
      life, physical functional limitations, and other variable. Demographic variables
      that influence RTW for persons with SCI include age at injury onset,
      chronological age, gender, education, ethnicity, marital status, and per-injury
      work intensity. Others include satisfaction, and adjustment to sustaining SCI. In
      an effort to enhance employment opportunities for individuals with disabilities
      including SCI, Ticket to Work Incentive Improvement Act of 1999 (TWILA) has been
      passed by Congress and some states have begun implementing targeted initiatives
      through the State Partnership Systems Change Initiatives (SPI). Future research
      directions are recommended in light of recent legislative initiatives.

PMID- 12237498
TI  - Impact of minority status following traumatic spinal cord injury.
AB  - OBJECTIVE: To interpret the data from the Spinal Cord Injury-Model Systems as it
      applies to demographics, incidence and functional outcomes of minority patients
      with spinal cord injury. DESIGN: Retrospective analysis of patients admitted to
      acute inpatient rehabilitation Spinal Cord Injury Model Systems Centers. RESULTS:
      Descriptive statistics including means, standard deviations, and proportions were
      computed for all relevant variables. Participants were grouped into two
      categories for purposes of analysis, non-minorities (white) and minorities, who
      were >90% African American. Differential statistics were used for comparisons
      with regard to demographics, etiology, sponsor of care, length of stay, charges,
      ASIA Motor Index scores, and FIM scores. Categorical data was analyzed using chi
      square analyses while continuous data were analyzed using ANOVA procedures.
      Analyses revealed significant differences between minorities and non-minorities
      in terms of age at injury, gender, marital status, employment status, education
      level, health insurance provider, injury severity, etiology, and discharge
      disposition. CONCLUSION: Analysis of the data indicates that violence is the
      leading single cause of spinal cord injury in minority patients admitted to the
      model systems centers. The majority of patients who sustained spinal cord injury
      secondary to violence were minorities with the following demographics: young,
      single, unemployed males, with less than a high school education, residing in an
      urban area.

PMID- 12237499
TI  - Current directions in computer-assisted cognitive rehabilitation.
AB  - Technological advances over the past decade have given rise to the development of
      multiple computer-assisted cognitive rehabilitation programs. While results of
      investigations examining the efficacy of such techniques have been mixed, a
      positive trend for utilization of these procedures has been demonstrated. This
      review provides a discussion of the progression of research in this area, from
      anecdotal studies to controlled empirical investigations. Methodological
      shortcomings are examined and directions for future research in computer-assisted
      cognitive rehabilitation suggested.

PMID- 12237500
TI  - The effect of cognitive education on the performance of students with
      neurological developmental disabilities.
AB  - A cognitive education program was developed to facilitate acquisition of
      cognitive skills and address the learning deficits of adolescent students with
      neurological, developmental disabilities, and autism. This study examined the
      outcomes of incorporating mediated cognitive education into special education
      classrooms. Cognitive education provided cognitive training utilizing REHABIT
      materials through mediated teaching. Following a matched pair model, forty-six
      students were assigned to either a treatment or a control group. All students
      received weekly instruction in Individual Educational Program (IEP) goals.
      Curriculum areas included IEP objectives in reading, math, social skills, health,
      science and social studies. Students in the control group received regular
      classroom instruction. Students in the treatment group participated in cognitive
      educated one hour per week replacing thirty minutes of reading and thirty minutes
      of math. Pre and posttest comparisons on measures of intelligence, achievement
      and adaptive behavior showed those students in the treatment group attained
      higher scores across measures.

PMID- 12237501
TI  - Systematic muscle building exercises in the rehabilitation of stroke patients.
AB  - The effects of targeted strength training in patients with muscle weakness of
      central origin following cerebrovascular accidents has hardly been investigated
      to date. This prospective non-randomized study of 56 patients was designed to
      shed light on the effects of strength building exercises on muscle tone and on
      the gain in muscle strength achieved with them. All patients underwent a full
      residential neurologic rehabilitation program for 4 weeks, which included an
      exercise program for restoring the extensor strength of the legs and the
      supporting strength of the arms by leg and arm presses. Throughout the
      rehabilitation program muscle spasticity was evaluated clinically and maximal
      muscle strength on completion of the exercise program was compared to baseline.
      The extensor strength of the legs increased by 31.0 (+/- 26.7)% by 40.2 (+/-
      15)%. significant for both variables. The extent of strength gain was positively
      correlated with the intensity and the number of exercising units. Muscle tone,
      which was abnormally high at baseline, did not further increase in any one case.
      The results of this study showed that targeted strength training significantly
      increased muscle power in patients with muscle weakness of central origin without
      any negative effects on spasticity.

PMID- 12237502
TI  - When should upper limb function be trained after stroke? Evidence for and against
      early intervention.
AB  - Very little time is available for arm and hand training while patients are in
      hospital after stroke. Therapeutic strategies that use intensive practice in the
      early days and weeks after stroke may improve the recovery of upper limb
      function. This paper considers the physiology of the brain in acute stroke and
      evaluates the evidence for and against early intensive activity of the upper limb
      as an essential precursor to any decision to invest in increased activity.

PMID- 12237503
TI  - The effect of predictable and unpredictable motor tasks on postural control after
      traumatic brain injury.
AB  - This study examined the effects of environmental predictability on postural
      control during functional reaching while seated in healthy individuals and
      patients with traumatic brain injury (TBI). The postural perturbation used
      required reaching to the left versus reaching to the right, while seated, under
      predictable versus unpredictable conditions. Indexes of postural control-
      trajectory stability and response reach times--were measured using an
      electromechanical system in ten patients with TBI and ten healthy subjects. In
      the TBI group, greater trajectory stability and shorter response reach time were
      recorded under unpredictable conditions when reaching to both the right and left
      (d-index 0.57-2.3). In the control group, greater trajectory stability and
      shorter response time were recorded under predictable and unpredictable
      environments compared with the TBI group (d-index 0.46-0.95). This study refutes
      the hierarchical, predictable-to-unpredictable-environment model of postural
      control evaluation and treatment. The relationship between information processing
      demands and postural skill appears more complex than a simple linear association.
      Predictable and unpredictable conditions may be used concurrently, not
      sequentially, in TBI rehabilitation.

PMID- 12237504
TI  - Vegetative state and minimally responsive patients--regional survey, long-term
      case outcomes and service recommendations.
AB  - A regional survey of Consultant level Neurology, Neurosurgical and Rehabilitation
      staff identified a retrospective estimate of patients in vegetative or minimally
      responsive states from their own clinical caseloads (October 1995--97). 35
      patients were identified; the majority of whom were not currently placed in
      specialist brain injury facilities following acute hospital intervention. In
      addition, a retrospective review of referrals to this unit (1995--2001) was also
      undertaken. Of twelve patients referred as being in a vegetative or minimally
      responsive state, 4 were considered as having been misdiagnosed (emerged) at
      follow-up; 2 had been presumed to be vegetative for at least one year. All
      patients remained severely physically disabled (i.e., totally dependent for care)
      but four were nevertheless able to communicate their preference in quality of
      life issues, care decisions etc. either by verbal or non-verbal means. Vegetative
      minimally responsive patients or those who are very severely and multiply
      disabled need skilled and frequently prolonged assessment. Appropriate management
      requires an experienced inter-disciplinary as opposed to multidisciplinary team
      working style, whose skill repertoire equips them to recognise often-subtle
      improvements in cognitive function and act to maximise individual patient's
      quality of life. The current paucity of service provision for this vulnerable
      group of patients is highlighted.

PMID- 12237505
TI  - Acoustic analysis of parkinsonian speech I: speech characteristics and L-Dopa
      therapy.
AB  - This paper reviews the literature pertaining to Parkinson's disease (PD) and the
      speech dysfunction typically associated with PD, including the effects on
      respiration, phonation, articulation, resonance, and prosody. The effect of
      treatment with the drug L-Dopa is also examined, along with the effect of L-Dopa
      treatment on Parkinsonian speech. This paper is the first of a two-part series.
      Part two examines the literature pertaining to the fluctuations that can occur
      during treatment with L-Dopa, the speech changes associated with these
      fluctuations, and methodological issues affecting the examination of fluctuations
      and PD speech.

PMID- 12237506
TI  - Acoustic analysis of parkinsonian speech II: L-Dopa related fluctuations and
      methodological issues.
AB  - The drug L-Dopa is used in the treatment of Parkinson's disease (PD), and
      patients often experience fluctuations in performance after a period of time
      taking L-Dopa. This paper reviews the literature pertaining to these
      fluctuations. While a number of researchers have examined L-Dopa related
      fluctuations in general, these fluctuations have rarely been addressed in speech
      research. To examine the effect of L-Dopa related fluctuations a number of
      methodological issues need to be addressed including time of day, anxiety level,
      disease stage, and drug regimen differences. Strategies are proposed for
      addressing these methodological issues in studying the effects of L-Dopa
      fluctuations on PD speech. This paper is part two of a two part series; Part one
      examined PD and PD speech in general, along with L-Dopa treatment, and the
      effects of L-Dopa treatment on speech.

PMID- 12237507
TI  - The validity of the GaitRite and the Functional Ambulation Performance scoring
      system in the analysis of Parkinson gait.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was (1) to determine the
      validity of the GaitRite System in detecting footfall patterns and selected gait
      characteristics of person with early stage Parkinson's disease (PD) and (2) to
      investigate whether the Functional Ambulation Performance (FAP) scoring system is
      a valid tool to distinguish between selected gait characteristics of patients
      with early stage Parkinson's disease and similar age of non-impaired individuals.
      The FAP score is a quantitative means of assessing gait based on specific spatial
      and temporal gait parameters. PARTICIPANTS: 11 volunteers with idiopathic
      Parkinson's disease, (mean age = 74.3), and 11 age matched volunteers, (mean age
      = 70.3), with no history of neurological disorder participated in the study. The
      non-impaired control group were not matched in age and sex but of similar age and
      males and females were represented in the control group. METHODS: Temporal and
      spatial parameters of gait were analyzed for both preferred- speed and fast-speed
      walking using the computerized GaitRite system. The system integrates specific
      components of locomotion to provide a single, numerical representation of gait,
      the Functional Ambulation Performance Score (FAP) score. RESULTS: The most
      powerful and discriminating variable between Parkinson's and non-impaired groups
      for both walking speeds was the mean normalized velocity (MNV). Which is velocity
      divided by leg length. The MNV was 0.83 for PD at preferred walking speed and
      1.14 at fast speed, the non-impaired group preferred-speed group walking was
      1.33, while fast-speed walking MNV was 1.70. Note the fast walking of PD was
      slower than the preferred velocity of the non-impaired group. For preferred-speed
      walking, all gait variables analyzed in the study were different between the two
      groups beyond the p < 0.05 level of confidence with the single exception of right
      stance percentage. For fast-speed walking, three of the entered variables did not
      discriminate between the two groups: the fast walking FAP score, left fast
      walking cadence, and right fast-walking single support percentage. CONCLUSION AND
      DISCUSSION: Our results indicate that persons with Parkinson's disease (PD)
      attain a significantly lower FAP score when ambulating at their preferred rate
      and demonstrate shorter step length and a longer step time than the age matched
      non-impaired group during both preferred and fast velocities of walking. Stance
      duration and double support duration were increased for the Parkinson's
      population, whereas single support duration, mean cadence, and heel-to-heel base
      of support were markedly reduced for both walking speeds. The FAP score was
      significantly different from the non-impaired control group for preferred-speed
      walking. These results indicate that the GaitRite system can be useful in
      detecting footfall patterns and selected time and distance measurements of
      persons with early stage Parkinson's disease and the FAP score discriminates
      between the PD population and the non-impaired controls when walking at preferred
      rate but not at fast walking.

PMID- 12237508
TI  - Insulin-like growth factor-I as a possible hormonal mediator of nutritional
      regulation of reproduction in cattle.
AB  - The current review aims to establish insulin-like growth factor-1 (IGF-I) as the
      factor that signals nutritional status to the reproductive axis, and show that
      assessment of IGF-I in blood early postpartum during the negative energy balance
      (NEB) period could be used to predict both nutritional and reproductive status in
      dairy cattle. The review also explores the effect of nutritional status on
      circulating IGF-I concentrations and the endocrine role of IGF-I on the
      reproductive axis. IGF-I plays an important role in gonadotropin-induced
      folliculogenesis, ovarian steroidogenesis and corpus luteum (CL) function. It
      also modulates pituitary and hypothalamus function. IGF-I clearly has an
      endocrine role on the reproductive axis. Severe under nutrition significantly
      reduces plasma IGF-I concentrations. During the critical period of NEB in high
      yielding dairy cattle early postpartum, IGF-I concentrations are low in blood and
      its levels are positively correlated to energy status and reproductive function
      during this period. Changes in circulating IGF-I immediately postpartum may help
      predict both nutritional and reproductive status in dairy cattle. IGF-I is
      therefore one of the long sought factors that signal nutritional status to the
      reproductive axis.

PMID- 12237509
TI  - Improved monospermic fertilization and subsequent blastocyst formation of bovine
      oocytes fertilized in vitro in a medium containing NaCl of decreased
      concentration.
AB  - The objective of this study was to evaluate whether changes in NaCl concentration
      in a fertilization medium could improve normal fertilization and preimplantation
      development of bovine oocytes. In vitro matured bovine oocytes were inseminated
      with frozen-thawed semen for 18 hr in a Tyrode's medium with albumin, lactate and
      pyruvate (TALP), to which 114 (TALP-114), 96 (TALP-96) or 78 (TALP-78) mM NaCl
      was added. Presumptive zygotes were cultured for 192 hr in a modified TALP
      containing 90 mM NaCl, 1.5 mM glucose, 0.3% (w/v) BSA, minimal essential medium
      (MEM) essential and nonessential amino acids, and insulin-transferrin-selenium
      complex. Lower polyspermy rate was obtained by the insemination in TALP-96 (7.8
      +/- 2.3%) than by the insemination in TALP-114 (25.6 +/- 1.4%), without decrease
      in male pronucleus (MPN) formation. Fertilization in TALP-78 also yielded
      decreased polyspermic fertilization (3.8 +/- 1.5%), but significant decrease in
      MPN formation was found (63.1 +/- 3.1%). In preimplantation development, more
      blastocysts developed from oocytes inseminated in TALP-96 (24.1 +/- 1.7%) than
      from oocytes inseminated in TALP-114 (16.8 +/- 1.4%). TALP-78, however, did not
      improve preimplantation development beyond the 8-cell stage compared with TALP
      114. Mean cell number of blastocyst was higher when oocytes were fertilized in
      TALP-96 (137.0 +/- 4.5) than in TALP-114 (123.1 +/- 5.1) and in TALP-78 (102.3 +/
      4.5). These results demonstrate that insemination of bovine oocytes in a TALP
      with decreased NaCl concentration (96 mM) improves blastocyst formation and
      embryo viability. Decrease in NaCl concentration below 96 mM, however, may delay
      or inhibit MPN formation, and inhibits subsequent development in vitro.

PMID- 12237510
TI  - Determination of antigenic proteins of housedust mites in 90 dogs suffering from
      atopic dermatitis.
AB  - Housedust mites, Dermatophagoides pteronyssinus (D. pteronyssinus) and
      Dermatophagoides farinae (D. farinae), are the important causative agents of
      allergic diseases in human and animals. By using 165 dogs suffering from atopic
      dermatitis (AD), serum levels of immunogloblin E (IgE) antibody against 25 kinds
      of allergen including housedust mites were determined. Housedust mites were the
      most frequent allergen against which 90 of the 165 allergic dogs (54.5%) by
      IMMUNODOT assay. With the further analysis of immunoblotting assay in the 90 dogs
      sensitized with housedust mites, antigenic proteins of housedust mites recognized
      by IgE antibodies were with the apparent molecular masses of 15, 76, 90, 98, and
      170-kD. Among them, the 15-kD protein that might be identical to Group 2 antigens
      (Der f2, Der p2) was prominently observed (52/90). This study indicates that
      about a half of dogs with AD were sensitized to housedust mites, suggesting that
      Group 2 antigens of housedust mites may be a major allergen in canine AD.

PMID- 12237511
TI  - Thyroid hormone augments GLUT4 expression and insulin-sensitive glucose transport
      system in differentiating rat brown adipocytes in culture.
AB  - The effects of triiodothyronine (T3) on differentiation-dependent expression of
      GLUT and responses of glucose transport to insulin and norepinephrine (NE) were
      investigated. Precursor cells of brown adipocytes isolated from the interscapular
      brown adipose tissue of newborn rats were cultured in the absence or presence of
      various concentrations of T3. Western bolt analysis revealed that treatment with
      T3 resulted in an increased expression of GLUT4, in a dose-dependent manner,
      whereas GLUT1 contents were unchanged. In parallel with the increase in GLUT4
      expression, T3 improved insulin sensitivity for glucose transport, being
      accompanied by an increase in maximal transport rate and a reduction of ED(50).
      In contrast, T3-treatment of the brown adipocytes during the differentiation
      process had little effect on NE-regulatable glucose transport system. These
      results suggest that T3 plays a predominant role in the development of insulin
      sensitive glucose transport during differentiation of brown adipocytes.

PMID- 12237512
TI  - Analysis of serum cytokine profile in a holstein heifer with leukocyte adhesion
      deficiency which survived for long period.
AB  - Serum cytokine levels and their expression of mRNA on neutrophils from a bone
      marrow (BM) transplanted heifer with leukocyte adhesion deficiency were
      evaluated. The clinical condition of the affected heifer was relatively stable
      after BM-transplantation. Persistent hyper gamma-globulinemia and increased serum
      immunoglobulin G (IgG) concentrations were monitored longitudinally. The
      concentration of interleukin (IL)-1beta in serum from the affected heifer ranged
      from 15.8 to 321.7 ng/ml, and maximum concentration occurred at the time which
      coincided with peak IL-6. Serum levels of IL-6 ranged from 0.32 to 27.9 ng/m l,
      and they appeared to be associated with the increment of serum IgG in the
      affected heifer. mRNAs for IL-1beta, IL-6, IL-8 and granulocyte and macrophage
      colony stimulating factor (GM-CSF) were increased in neutrophils from the
      affected heifer compared to controls. Persistent hyper gamma-globulinemia of the
      affected heifer appeared to be associated with enhanced mRNA expression for IL-6
      and its serum levels. These findings suggest that humoral immunity of the
      affected heifer is activated and the production of neutrophils appears to be
      enhanced under the incapability of beta(2) integrin-mediated functions of
      phagocytic cells.

PMID- 12237513
TI  - Effects of epidermal growth factor on placental amino acids uptake in pregnant
      rats.
AB  - To evaluate the effects of epidermal growth factor (EGF) on placental amino acids
      uptake, transport activities for L-proline, L-leucine, and L-alanine were
      kinetically examined in placental microvillous vesicles(PMV) obtained from
      pregnant rats administered with EGF(100 and 200 microg/kg/day) from day 18 to 21
      of pregnancy. The Vmax of Na(+)-dependent proline uptake remarkably increased
      with a dose-dependent manner of EGF, while Km did not change. In contrast, Vmax
      and Km values of Na(+)-dependent and -independent alanine, and Na(+)-independent
      leucine uptake were not affected. These results suggested that EGF enhanced
      proline transport activity in placental microvillous membranes, resulting in an
      increase of proline concentration in the fetal blood. The selective up-regulation
      of proline uptake was considered to contribute to fetal growth by EGF.

PMID- 12237514
TI  - Application of transarterial embolization of renal artery in rabbits with
      experimental hydronephrosis.
AB  - This study was performed to validate the procedure of transarterial embolization
      of the renal artery (TAE-RA) using iohexol-ethanol solution in rabbits with
      unilateral experimental hydronephrosis and to evaluate the embolized kidney and
      contralateral normal kidney using B-mode ultrasonography and color Doppler
      ultrasonography. Experimental hydronephrosis was induced at 17 days after
      ligation of unilateral ureter in 13 rabbits. Renal artery embolization was
      performed using selective catheterization in the hydronephrotic kidney of eight
      rabbits and electrocardiography, oxygen saturation, body temperature, pulse, and
      respiratory rate were within normal ranges during procedures. Iohexol-ethanol
      solution was used as embolic material. Average ethanol dose for renal artery
      embolization was 1.4 +/- 0.7 ml/kg. There were no rabbits expired after TAE-RA
      and no side effects associated with regurgitation of iohexol-ethanol solution. In
      color Doppler ultrasonographic findings, there was no blood flow into the
      embolized kidneys treated by TAE-RA, however, blood flow signal was found in
      hydronephrotic kidney not treated by TAE-RA. Ultrasonographically, the mean
      longitudinal length of the embolized kidney significantly decreased at 2 and 3
      months after TAE-RA. No significant difference of resistive index values was
      found between contralateral normal kidney of rabbits treated by TAE-RA and
      contralateral normal kidneys of rabbits treated with nephrectomy. We may conclude
      that TAE-RA with iohexol-ethanol solution is a viable alternative to nephrectomy
      in rabbits with unilateral hydronephrosis.

PMID- 12237515
TI  - Evaluation of isotonic sodium bicarbonate solution for alkalizing effects in
      conscious calves.
AB  - After intravenous (i.v.) infusion of various volumes of 1.35%-isotonic sodium
      bicarbonate solution (ISB), acid-base equilibrium, blood pressure, plasma volume
      and biochemical parameters in healthy Holstein calves were studied. Four calves
      each were randomly assigned to the low-dose (LD; i.v. infusion of 5 ml/kg ISB),
      middle-dose (MD; i.v. infusion of 10 ml/kg ISB) and the high-dose groups (HD;
      i.v. infusion of 15 ml/kg ISB). Administration volumes of ISB in the LD, MD and
      HD groups were decided based on the first half volumes of 5, 10 and 15 mEq of
      base requirement by the acceptable equation. Systemic, pulmonary artery and
      central venous pressures, cardiac output and plasma osmotic pressure were not
      changed by ISB infusion and remained constant throughout the experiment for all
      groups. There was good correlation (r(2) = 0.950) between relative changes in
      base excess and infused volume of bicarbonate (y=2.491x). The coefficient of
      distribution for bicarbonate ions was calculated to be 0.401 (=1/2.491).
      Therefore, it is suggested that a value of 0.4 would be most appropriate when
      calculating the base requirements in calves. Therefore, the first half volumes of
      ISB correcting base deficits of 5, 10 and 15 mEq in calves were estimated to be
      6, 12 and 18 ml/kg, respectively. On the basis of the findings in this study, ISB
      may be used to correct metabolic acidosis without altering the plasma osmotic
      pressure, hemodynamic status and respiratory function in the calves.

PMID- 12237516
TI  - The histological observations on the large intestine of the goose (Anser anser)
      during the pre- and post-hatching periods.
AB  - The development of the cecum and colon in the goose was investigated during the
      period from the 15th to 28th day of the incubation and from 1 to 30 days of age
      after hatching by light microscopy. By day 15 of the incubation, in the cecum and
      colon, the lumen was surrounded by pseudostratified epithelium. The previllous
      ridges appeared at 15th and 17th days of the incubation in the colon and ceca,
      respectively. At the base of previllous ridges, the epithelium changed into a
      simple prismathic epithelium at 15th and 17th days of the incubation in the colon
      and cecum, respectively. The villi appeared at the 21st days of the incubation.
      The crypts and goblet cells appeared on the first day after hatching. In the pre
      hatching period, the lamina muscularis mucosa was present only in the colon. The
      submucosa consisted of loosely aggregated connective tissue in the pre-hatching
      period. In the post-hatching period, it consisted of a very thin layer of
      connective tissue. Its presence was only obvious where the cells of the
      submucosal nerve plexus or occasional large blood vessels considerably increased
      its thickness. The nerve plexus corresponding to the Auerbach's plexus of the
      mammalian intestine and submucosal nerve plexus appeared by 15th days of the
      incubation. From the 15th to 28th day of incubation, the tunica muscularis
      consisted of circular smooth muscle cells in the ceca. On the 28th day of the
      incubation a thinner longitudinal muscle layer added to the circular muscle
      layer. In the colon there was an outer longitudinal and a thicker circular muscle
      layer.

PMID- 12237517
TI  - The respiratory burst activity of bottlenose dolphin neutrophils elicited by
      several stimulants.
AB  - To investigate the early host defense function in aquatic animals, the
      respiratory burst activity of bottlenose dolphin neutrophils against soluble and
      particulate stimulants was measured by luminol-dependent chemiluminescence assays
      and compared with those of bovine and human. Dolphin neutrophils generated the
      respiratory burst in response to phorbol 12-myristate 13-acetate (PMA),
      concanavalinA (ConA), heated-plasma (HP), and homologous-plasma opsonized zymosan
      except N-formyl-Met-Leu-Phe (fMLP). However, the respiratory burst of dolphin
      neutrophils stimulated by lipopolysaccharide and Staphylococcus aureus was
      inferior to those of bovine and human. Furthermore, DP-OZ also induced the
      respiratory burst of bovine and human neutrophils. In conclusion, dolphin
      neutrophils responded to several soluble and particulate stimulants as well as
      human neutrophils, but were refractory or slightly responded to bacterial agents.

PMID- 12237518
TI  - Molecular epidemiology of VapA-positive Rhodococcus equi in thoroughbred horses
      in Kagoshima, Japan.
AB  - The prevalence of virulent R. equi having 15- to 17-kDa antigens (VapA) in fecal
      isolates from 13 thoroughbred foals and their dams on 5 farms in Kagoshima,
      Japan, and the plasmid profiles of VapA-positive isolates by restriction fragment
      digestion patterns were investigated to compare the genotypic variation among
      virulence plasmids of R. equi isolates from Japan. In total, 218 (24.6%) of 886
      isolates from the feces of the 13 foals and 13 (12.5%) of 104 isolates from the
      feces of their dams demonstrated VapA-positive R. equi. Plasmid DNA preparations
      of 231 virulent isolates from foals and dams were analyzed by restriction enzyme
      digestion with endonucleases EcoRI, EcoT22I and HindIII and were divided into 3
      types: 172 isolates contained a 90-kb type I plasmid, 57 contained a 90-kb type
      III plasmid and 2 contained a 90-kb type IV plasmid. This study demonstrates a
      geographic character in the distribution of virulence plasmids found in VapA
      positive isolates from thoroughbred foals in Kagoshima.

PMID- 12237519
TI  - Effect of germanium, poly-trans-[2-carboxyethyl] germasesquioxane on natural
      killer (NK) activity in dogs.
AB  - In an attempt to study the immunological effects on normal and adenocarcinoma
      (AC) dogs, the natural killer (NK) activity was determined. Augmentation of NK
      cell activities in responsive normal and AC dogs that indicatedanergy in the
      phaseolus vulgaris agglutinin (PHA) skin-test was manifested when the animals
      were accordingly treated with germanium (GN).

PMID- 12237520
TI  - Effects of chlorpromazine, pentoxifylline and dexamethasone on mRNA expression of
      lipopolysaccharide-induced inflammatory cytokines in bovine peripheral blood
      mononuclear cells.
AB  - The effects of chlorpromazine (CPZ), pentoxifylline (PTX) and dexamethasone (DEX)
      on mRNA expression of lipopolysaccharide (LPS)-induced proinflammatory cytokines
      were examined in bovine peripheral blood mononuclear cells (PBMCs) in vitro. The
      expression of inflammatory cytokine mRNAs was analyzed by RT-PCR and Southern
      blot hybridization in bovine PBMCs. CPZ and DEX decreased the expression of
      cytokine mRNA (such as interleukin-1 beta and tumor necrosis factor-alpha) after
      stimulation with LPS in a dose-dependent manner. However, pretreatment with PTX
      had no inhibitory effect on the mRNA expression of proinflammatory cytokines.
      These results indicated that pretreatment with CPZ and DEX might be effective to
      reduce the production of LPS-induced inflammatory cytokines in bovine PBMCs in
      vitro.

PMID- 12237521
TI  - Detection of equine Babesia spp. gene fragments in Dermacentor nuttalli Olenev
      1929 infesting mongolian horses, and their amplification in egg and larval
      progenies.
AB  - Babesia equi (EMA-1) and Babesia caballi (BC48) gene fragments were amplified by
      polymerase chain reaction (PCR), in blood samples, and partially fed-females and
      egg and larval progenies of Dermacentor nuttalli, collected from horses in
      Altanbulag, Tuv Province, Mongolia. While Babesia parasite DNA was detected in
      some horse blood samples during the first PCR, all positive cases in partially
      fed-female ticks, eggs and larvae were confirmed by nested PCR. Present study
      reinforces earlier similar findings in unfed D. nuttalli ticks collected from an
      open space vegetation in Bayanonjuul, Tuv Province in Central Mongolia, pointing
      to the most likely important role of D. nuttalli in the transmission of equine
      babesiosis in Mongolia. The detection of parasite DNA in eggs and larval
      progenies is likewise suggestive of transovarial parasite transmission in this
      tick species.

PMID- 12237522
TI  - Plasma steroid profiles following follicle-stimulating hormone or equine
      chorionic gonadotropin injection in cows chronically treated with gonadotropin
      releasing hormone agonist.
AB  - Plasma steroid profiles following follicle-stimulating hormone (FSH) or equine
      chorionic gonadotropin (eCG) injection were studied in chronically gonadotropin
      releasing hormone agonist (GnRH-A)-treated cows. Follicular development and irINH
      secretion were stimulated by FSH or eCG injection. The plasma concentrations of
      estradiol-17 beta (E(2)) and testosterone (T) were markedly increased following
      eCG injection. However, significant increases of the plasma E(2) and T
      concentrations were not detected in FSH-treated cows. Ovulation of developed
      follicles were depended on the hCG injection in both groups. These results show:
      1) Follicular response to an exogenous gonadotropin is still remained, 2)
      Ovulation of developed follicles is induced by hCG injection and 3) FSH and eCG
      cause disparate plasma steroid profiles, under the influence of repeated GnRH-A
      treatment.

PMID- 12237523
TI  - Serological survey of leptospirosis in sows with premature birth and stillbirth
      in Chiba and Gunma prefectures of Japan.
AB  - In 1996 and 1997, the seroprevalence against Leptospira in parturient sows with
      premature birth or stillbirth from two herds was investigated. In three out of
      four sow serum samples obtained in Gunma Prefecture, the antibody titers to
      Leptospira interrogans serovar copenhageni (M20) were higher than 10,000 (the
      reciprocal of the serum dilution). Furthermore, the antibody titers to L.
      interrogans serovar canicola (Hond Utrecht IV) were significantly high in the
      three sows and the titers ranged from 1,000 to 3,000. In sows obtained in Chiba
      Prefecture, significantly high antibody titers to serovar copenhageni (M20) were
      confirmed in eight out of 40 sows, and antibody titers greater than 10,000 in six
      of them. Significantly high antibody titers to L. interrogans serovar
      icterohaemorrhagiae (RGA) and L. canicola (Hond Utrecht IV) were confirmed in
      four and 18 out of the 40 sows, respectively, compared with the titers to the
      other serovars. These findings may indicate the prevalence of leptospirosis in
      pig herds in both Gunma and Chiba Prefectures.

PMID- 12237524
TI  - Production and characterization of biodegradable Povidone-iodine microsphere as a
      intramammary disinfectant.
AB  - Microspheres composed of biocompatible, biodegradable poly DL-lactide-co
      glycolide (DL-PLGA) and Povidone-iodine were evaluated as an intramammary
      disinfectant delivery system in vitro prior to infusion into mammary glands.
      Microsphere was prepared by solvent evaporation method and particle size,
      morphology and in vitro release kinetics were examined. The microspheres were
      ranged in size from 25 microm to 155 microm (mean diameter = 65.7 microm).
      Povidone-iodine was dispersed on the surface of microsphere and microsphere was
      spherical in shape with a smooth surface. The yield of microsphere was 57.3% and
      the encapsulation efficiency was 69.6%. In in vitro release study, a burst effect
      (50.9%) was observed during the first two days and a sustained release then
      continued for the next 28 days. Results of the present study demonstrated that
      microsphere have the potential for new intramammary disinfectant formulations
      that can provide increased efficacy of therapy against mastitis pathogens.

PMID- 12237525
TI  - Hepatic lymphangiomatosis in a young dog.
AB  - A 9-month-old intact male American cocker spaniel was referred because of
      hepatomegaly and ascites. Ultrasonographic evaluation of the liver revealed
      congestion and increased parenchymal echogenicity with focal and more hyperechoic
      nodules. Histopathology of the hepatic lesion revealed diffuse, ill-defined
      vascular proliferation. A single layer of endothelial cells, which showed signs
      of minimal cellular atypia, lined the irregular vessels. On immunohistochemistry,
      the proliferative endothelial cells lining the irregular vessels were positive
      for an antiserum to factor VIII related antigen. Based on these findings, the dog
      was diagnosed with hepatic lymphangiomatosis.

PMID- 12237526
TI  - Sequence comparison of the dopamine receptor D4 exon III repetitive region in
      several species of the order Carnivora.
AB  - It was previously demonstrated that the dog dopamine receptor D4 (DRD4) gene is
      polymorphic in terms of the repeat number and/or order of 39- and 12-bp sequences
      located in the third exon. To examine whether or not the repetitive region is
      present in other species of the order Carnivora, the homologous region of DRD4
      genes were sequenced in the gray wolf, raccoon dog, Asiatic black bear, common
      raccoon and domestic cat. In the family Canidae, the wolf had an identical
      sequence to that of the dog 447b allele, and a repetitive sequence similar to the
      dog DRD4 was also recognized in the raccoon dog. On the other hand, no obvious
      repeated structure was observed in the sequences of the bear, raccoon and cat.

PMID- 12237527
TI  - Physical properties of phosphatidylcholine vesicles containing small amount of
      sodium cholate and consideration on the initial stage of vesicle solubilization.
AB  - The effects of sub-solubilizing concentrations of sodium cholate (Na-chol) on
      several physicochemical properties of phosphatidylcholine (PC) small unilamellar
      vesicles (SUV) were considered in connection with the initial stage of membrane
      solubilization. ESR spectra of 12-doxylstearic acid (12-DS) in
      phosphatidylcholine from egg yolk (EPC) or dimyristoylphosphatidylcholine (DMPC)
      SUV at low concentrations (insufficient to destroy the vesicles) of Na-chol were
      composed of two (a strongly immobilized and an additional weakly immobilized)
      immiscible components. The origin of the additional bands was phase separation
      which occurred in the hydrophobic parts of PC SUV in the presence of Na-chol.
      Differential scanning calorimetry measurements demonstrated that the mixed
      DMPC/Na-chol SUV possessed two (a sharp low-temperature and a broad high
      temperature) endothermic peaks, which is consistent with the coexistence of two
      immiscible phases in the vesicular membranes. zeta Potentials of the EPC/Na-chol
      SUV revealed that high anionic densities appeared on the surfaces of the SUV at a
      Na-chol concentration slightly below the upper boundary of the vesicle region.
      Thus, the initial stage of the solubilization of PC SUV by Na-chol was caused by
      the aggregation of hydrophobic parts of PC membranes, followed by the occurrence
      of high anionic densities on the surfaces of the vesicles. The fact that removal
      of Na-chol from PC/Na-chol mixed systems preferentially resulted in the formation
      of small vesicles might originate from these anionic charges.

PMID- 12237528
TI  - Pharmacological studies and synthesis of morpholino alkyl derivatives.
AB  - Seven morpholin derivatives were synthesized (compounds 1-7) and their
      behavioural effects were evaluated; the elements considered were locomotor
      activity, motor coordination, catalepsy, stereotyped behaviour and
      antinociception. All the compounds, at doses of 10-20-40 mg/kg/i.p., induced a
      reduction of all behavioural elements without a significant antinociceptive
      effect. These results indicate that these morpholin derivatives affect the
      central nervous system.

PMID- 12237529
TI  - Influence of physical parameters and lubricants on the compaction properties of
      granulated and non-granulated cross-linked high amylose starch.
AB  - Cross-linked high amylose starch (CLA) is a pharmaceutical excipient used in
      direct compression for the preparation of controlled release tablets and
      implants. In this work the compression properties of CLA in bulk and granulated
      forms (without binder) were evaluated for the first time. Tablets were prepared
      on an instrumented single punch machine. The flow properties and the compression
      characteristics (compressibility, densification behavior, work of compression) of
      the materials as well as the mechanical strength of the finished compacts
      (compactibility) were systematically examined. Wet granulation was found to
      improve the flowability and the compressibility of CLA but concomitantly reduced
      its compactibility. It was demonstrated that CLA was a plastically deforming
      material with a plasticity index and a yield pressure value comparable to those
      of pregelatinized starch. The compactibility of granulated CLA was independent of
      particle size in the range of 75 to 500 microm, but slightly decreased when the
      percentage of the fine particles (<75 microm) in the bulk powder was increased.
      Water and colloidal silicone dioxide facilitated the consolidation of CLA, while
      magnesium stearate had an opposite effect on the tablet crushing force.

PMID- 12237530
TI  - Synthesis and cyclic AMP phosphodiesterase 4 isoenzyme inhibitory activity of
      heterocycle condensed purines.
AB  - To reverse the adverse reactions of alkylxanthines and to develop novel
      inhibitors of cyclic AMP phosphodiesterase 4 (PDE4), a series of heterocycle [a]
      , [b]-, [c,d]-, and [i]-condensed purines were designed and synthesized. Although
      all compounds did not display PDE1 and PDE3 inhibitory activities, several
      heterocycle [i]-condensed purines strongly inhibited PDE4. Especially, dl-3,4
      dipropyl-8-methyl-4,5,7,8-tetrahydro-1H-imidazo[2,1-i]purin-5-one (dl-7c)
      exhibited comparable PDE4 inhibitory activity (IC(50)=1.9 microM) to rolipram and
      denbufylline (DBF).

PMID- 12237531
TI  - Design of controlled release system with multi-layers of powder.
AB  - Pellets containing active ingredients were coated with water-insoluble powders,
      i.e. hydrogenated caster oil (Lubliwax (WAX)) and magnesium stearate (Mg-St). The
      influences of the structural difference of the sustained release layer and curing
      conditions on the drug release rate were investigated. Sodium valproate (VP-Na)
      was used as a highly water-soluble model drug. Drug release profiles were
      influenced by the combination of the WAX layer and the Mg-St layer. Even if the
      formula of sustained release layers were the same, drug release rate could be
      affected by the structural difference of the controlled release layer. The Mg-St
      layer was more effective in prolonging drug release than the WAX layer. Compared
      with single and double layer types, the triple layer (sandwich) type was most
      effective in obtaining a long sustained drug release. Heat-treatment retarded
      drug release mainly by increasing the density of the sustained release layer of
      the WAX. The Mg-St was effective in protecting the agglomeration between
      particles during heat-treatment. Optimal heat-treatment conditions were found to
      exist. Scanning electron microscopy (SEM) analysis indicated that heat-treatment
      caused the WAX to melt, formed a film-like structure and made the release layer
      dense. Furthermore, heat-treatment changed the release pattern of VP-Na from
      sustained release pellets with a multi-layer of powder, leading to zero-order
      release.

PMID- 12237532
TI  - Mass variation tests for coating tablets and hard capsules: rational application
      of mass variation tests.
AB  - The mass variation test is a simplified alternative test version of the content
      uniformity test. In the case of coating tablets and capsules, the mass variation
      test is principally applied to test the inner cores or fillings containing the
      active ingredient. However, some exceptions exist in pharmacopoeias. The effects
      of tablet coating and capsule shell on the results of the mass variation test
      were studied. The mass variation of outer crusts (coatings, capsule shells) and
      inner cores (core tablets, fillings) was measured separately in several products.
      The effects of coating on weight variability were very large for sugar-coated
      tablets. Relative standard deviation (RSD) of the formulation weight (RSD(W)) of
      sugar-coated tablets (2.73%) was larger than that of plain tablets (0.77%). The
      cause of the large RSD(W) is the large variation the weight of sugar-coating
      accounting for 44% of formulation weight. In the case of film-coated tablets, the
      effect of coating weight on the mass variation test was very small because the
      rate of coating in comparison to the whole weight was small. In the case of hard
      capsules, the usage of whole formulation weight resulted in underestimation of
      variations of filling weight. The differences between dosage forms in the
      applicability of the mass variation test are caused by differing weight
      proportions and variability of the outer coatings or shells. To avoid the
      underestimation of mass variation for hard capsules, a corrected acceptance value
      is useful. For all the dosage units, the mass variation test can principally be
      applied to determine which mass is expected to be proportional to the content of
      the active ingredient. However, some modification of acceptance values enables
      application of the mass variation tests to inapplicable cases, such as when the
      RSD of drug concentration (RSD(C)) is larger than 2%.

PMID- 12237533
TI  - Evaluation of the disintegration time of rapidly disintegrating tablets via a
      novel method utilizing a CCD camera.
AB  - Many kinds of rapidly disintegrating or oral disintegrating tablets (RDT) have
      been developed to improve the ease of tablet administration, especially for
      elderly and pediatric patients. In these cases, knowledge regarding
      disintegration behavior appears important with respect to the development of such
      a novel tablet. Ordinary disintegration testing, such as the Japanese
      Pharmacopoeia (JP) method, faces limitations with respect to the evaluation of
      rapid disintegration due to strong agitation. Therefore, we have developed a
      novel apparatus and method to determine the dissolution of the RDT. The novel
      device consists of a disintegrating bath and CCD camera interfaced with a
      personal computer equipped with motion capture and image analysis software. A
      newly developed RDT containing various types of binder was evaluated with this
      protocol. In this method, disintegration occurs in a mildly agitated medium,
      which allows differentiation of minor distinctions among RDTs of different
      formulations. Simultaneously, we were also able to detect qualitative
      information, i.e., morphological changes in the tablet during disintegration.
      This method is useful for the evaluation of the disintegration of RDT during
      pharmaceutical development, and also for quality control during production.

PMID- 12237534
TI  - Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as a factor
      Xa inhibitor II. Substituent effect on biological activities.
AB  - Intravascular clot formation is an important event in a number of cardiovascular
      diseases. The prevention of blood coagulation has become a major target for new
      therapeutic agents. Factor Xa (FXa) is a trypsin-like serine protease that plays
      a key role in the blood coagulation cascade and represents an attractive target
      for anticoagulant drug development. We have investigated substituents in the
      central part of a lead compound (3: M55113), and discovered that compound M55551
      (34: (R)-4-[(6-Chloro-2-naphthalenyl)sulfonyl]-6-oxo-1-[[1-(4-pyridinyl)-4
      piperidinyl]methyl]-2-piperazinecarboxylic acid) is a potent inhibitor of FXa
      (IC(50)=0.006 microM), with high selectivity for FXa over trypsin and thrombin.
      The activity of this compound is ten times more powerful than the lead compound.

PMID- 12237535
TI  - Sesquiterpenes and alkaloids from Lindera chunii and their inhibitory activities
      against HIV-1 integrase.
AB  - Three new eudesmane type sesquiterpenoid lindenanolides E (1), F (2) and G (3),
      and two new aporphine alkaloid lindechunines A (18) and B (20) were isolated from
      roots of Lindera chunii MERR., together with seven known sesquiterpenes including
      a new naturally-occurring lindenanolide H (4) and eight known aporphine
      alkaloids. The structures of these compounds were determined by spectroscopic
      means. Of the isolated compounds, hernandonine (14), laurolistine (16), 7
      oxohernangerine (17) and lindechunine A (18) showed significant anti-human
      immunodeficiency virus type 1 (HIV-1) integrase activity with IC(50) values of
      16.3, 7.7, 18.2 and 21.1 microM, respectively. The major alkaloids presented in
      the roots of L. chunii were quantitatively analyzed by an HPLC method.

PMID- 12237536
TI  - Gentamicin sulphate release from a modified commercial acrylic surgical
      radiopaque bone cement. I. Influence of the gentamicin concentration on the
      release process mechanism.
AB  - The purpose of the present work was the study of the gentamicin sulphate (GS)
      release from a commercial acrylic bone cement CMW-1 with the aims of establishing
      the influence of the slabs preparation as well as the release mechanism and
      kinetics. The effect of the amount of GS on the release kinetic parameters has
      been also investigated. In vitro release studies were performed in a buffered
      saline solution at pH 7.4 and 37 degrees C. The GS concentration was determined
      using an indirect spectrophotometric method with an o-phthaldialdehyde as a
      derivatizing reagent. A commercial and three modified samples were tested. The
      free and fractured surfaces of the GS cement slabs before and after the release
      studies were observed by means of scanning electron microscopy (SEM). For low GS
      concentration loading the release was very incomplete because most of the GS
      beads were encapsulated by the hydrophobic PMMA matrix. A higher amount of
      antibiotic was released from cement that has a higher amount incorporated. A
      model and therefore a mechanism of release based on this model have been
      proposed. It has allowed us to explain the changes in dissolution kinetics of an
      acrylic matrix type controlled release system up to 12% GS loading. The
      cumulative amount of GS released M(t)/M(i), was fitted as a function of time. For
      lower amounts of GS, the regression analysis (R(2)>0.99) revealed that the
      release is most adequately represented by M(t)/M(i)=b+kt(n), where b represents a
      burst effect. The goodness of fit decreases as the amount of GS increases. The
      influence of some other type of release mechanism for higher amounts of GS must
      be taken into account and a second model for the release, M(t)/M(i)=b+k x [1-exp(
      kt)], is proposed.

PMID- 12237537
TI  - Dynamic characteristics of a peptide-binding groove of human HLA-A2 class I MHC
      molecules: normal mode analysis of the antigen peptide-class I MHC complex.
AB  - Class I major histocompatibility complex (MHC) binds antigen peptides with
      various sequences. We performed a normal mode analysis of HLA-A2 MHC that binds
      three peptides with different affinity. HLA-A2 MHC has a peptide-binding groove
      composed of two alpha-helices (residue 49-84, residue 140-179). Some residues in
      the center of the groove showed an increase in fluctuations and some residue
      pairs between two helix groups showed a negative change in correlations by
      removing the antigen peptide. The extent of the fluctuation and correlation
      changes correlated well with the experimental ranking of the three peptides in
      binding affinity. Some definite anti-correlative motions were found between two
      helix groups in low frequency modes (<50 cm(-1)) by removing the antigen peptide.
      We propose that the above anti-correlative motions play an important role to bind
      the antigen peptide, especially in obtaining a "dynamic fit."

PMID- 12237538
TI  - Studies on quinones. Part 37. Synthesis and biological activity of o-aminoester
      functionalised benzo- and naphtho[2,3-b]thiophenequinones.
AB  - The synthesis of 3-amino-2-methoxycarbonyl-4,7-dimethoxybenzo[b]thiophene (5) and
      benzothieno[3,2-d][1,3]oxazin 15 from 3,6-dimethoxy-2-nitrobenzaldehyde (1) is
      reported. Benzo[b]thiophene-4,7-quinones 9 and 10 were prepared in good yields by
      oxidative deprotection of the corresponding dimethoxybenzothiophenes 8 and 7.
      Cycloaddition reaction of quinone 8 with 1-(E)-trimethylsilyloxy-1,3-butadiene
      followed by acid-induced aromatization provides access to naphtho[2,3-b]thiophene
      4,9-quinone 13 and 14. The in vitro activity of the new quinones against
      Leishmania amazonensis and human-T-cell leukemia virus type 1 (HTLV-1) is
      reported.

PMID- 12237539
TI  - Release from or through a wax matrix system. IV. Generalized expression of the
      release process for a reservoir device tablet.
AB  - Generalization of the release process through the wax matrix layer was examined
      by use of a reservoir device tablet. The wax matrix layer of the reservoir device
      tablet was prepared from a physical mixture of lactose and hydrogenated castor
      oil to simplify the release properties. Release through the wax matrix layer
      showed zero-order kinetics in a steady state after a given lag time, and could be
      divided into two stages. The first stage was the formation process of water
      channel by dissolving the soluble component in the wax matrix layer. The lag time
      obtained by applying the square root law equation was well connected with the
      amount of the matrix layer and mixed weight ratio of components in this layer.
      The second stage was the zero-order release process of drug in the reservoir
      through the wax matrix layer, because the effective surface area was fixed. The
      release rate constants were connected with thickness of the matrix layer and
      permeability coefficient, and the permeability coefficients were connected with
      the diffusion coefficient of drug and porosity. Hence the release rate constant
      could be connected with the amount of matrix layer and the mixed weight ratio of
      components in the matrix layer. It was therefore suggested that the release
      process could be generalized using the amount of matrix layer and the mixed
      weight ratio of components in the matrix layer.

PMID- 12237540
TI  - Synthesis of N-substituted piperazinyl carbamoyl and acetyl derivatives of
      tetrahydropapaverine: potent antispasmodic agents.
AB  - The synthesis and structure-activity-relationship (SAR) for a series of N
      substituted piperazinyl carbamoyl 7-15 and piperazinyl acetyl 18-26 derivatives
      of tetrahydropapaverine have been carried out. The general synthetic methods of
      carbamoyl tetrahydropapaverine analogues involve N-substituted piperazines and
      carbamoyl imidazole tetrahydropapaverine as starting materials. Another route for
      synthesizing these compounds, involving the formation of carbamoyl imidazole
      piperazine has also been explored. Acylation of tetrahydropapaverine followed by
      substitution with various piperazinyl moities afforded the acetyl
      tetrahydropapaverine derivatives. Variously substituted piperazines have been
      used to monitor the effect of electron releasing and electron withdrawing
      substituents upon the antispasmodic activity of the molecules. Effect of varying
      electron densities on the antispasmodic activity, by altering the position of
      these groups on the benzene ring has also been monitored. Pharmacological methods
      involve the in vitro antispasmodic activity studies on a freshly removed guinea
      pig ileum using a force displacement transducer amplifier connected to a
      physiograph. Among the analogues synthesized in the present study, a promising
      compound 7, a potent muscle relaxant as compared to papaverine has been obtained.

PMID- 12237541
TI  - Preparation and biological activities of a bivalent poly(ethylene glycol) hybrid
      containing an active site and its synergistic site of fibronectin.
AB  - A bivalent poly(ethylene glycol) or PEG hybrid of fibronectin-related peptides
      was prepared. An active site peptide (RGD) and its synergistic site peptide
      (PHSRN) of fibronectin were conjugated with an amino acid-type PEG (aaPEG) to
      form PHSRN-aaPEG-RGD. A moderate spatial array between RGD and PHSRN in
      fibronectin may be required for synergic activity. The bivalent hybrid exhibited
      potent cell spreading activity and exhibited potent anti-metastatic activity in a
      model of experimental metastasis with B16-BL6 cells in mice. PEG may serve as a
      spacer for maintaining the desired spatial array.

PMID- 12237542
TI  - Development of a simple HPLC method for determination of paeoniflorin
      metabolizing activity of intestinal bacteria in rat feces.
AB  - A simple and reproducible HPLC method for the determination of paeoniflorin (PF)
      metabolizing activity of intestinal bacteria in rat feces was developed and
      validated. Orally administered PF, a major active constituent of Paeoniae Radix,
      is metabolized into a bioactive compound, paeonimetabolin I (PM-I) by intestinal
      bacteria. Direct determination of the PF-metabolizing rate into PM-I is hard to
      achieve by HPLC due to the lack of intense chromophore in PM-I. However, when PF
      was incubated with Lactobacillus brevis, an intestinal bacterium, in the presence
      of phenylmercaptan, the metabolizing rate of PF into 8-phenylthio-paeonimetabolin
      I (PT-PM-I) was found to be equivalent to that of PF into PM-I. Thus, the PF
      metabolizing activity of intestinal bacteria in rat feces was determined by
      measuring the rate of biotransformation of PF into PT-PM-I, which was detected by
      HPLC at 255 nm. This method can be utilized in the biopharmaceutical study of
      traditional Chinese formulations containing Paeoniae Radix.

PMID- 12237543
TI  - Physicochemical properties of PEG-grafted liposomes.
AB  - Egg phosphatidylcholine (EggPC) or dimyristoylphosphatidylcholine (DMPC)
      liposomes containing polyethylene glycol (PEG)-lipids covering a range of 0-30
      mol% have been prepared by Extrusion method. The physicochemical properties
      including size evolution and calcein permeation were evaluated to investigate the
      effect of PEG-lipids on bilayer structure. The results from quasielasetic light
      scattering (QELS), freeze-fracture microscopy, and gel exclusion chromatography
      revealed that presence of low concentration of PEG-lipid results in decreasing of
      vesicle size and further increase in the PEG-lipid concentrations lead to a
      transition from the lamellar membranes to micelles. The permeability for calcein
      increased with increase in concentration of distearoylphosphatidylethanolamine
      (DSPE)-PEG. On the other hand, the permeability decreased with low amount of
      cholesterol-PEG (blow 20% cholesterol-PEG) and increased with high amount of it.
      The maximum concentration of PEG-lipid that may be incorporated without
      alteration of the liposome structure depends on the composition of the bilayer.
      The concentration of DSPE-PEG2000 incorporated into vesicles without damaging
      vesicle structures were <20 mol% for EggPC and <10% for DMPC.

PMID- 12237544
TI  - Eucosterol oligoglycosides isolated from Scilla scilloides and their anti-tumor
      activity.
AB  - Two new eucosterol oligoglycosides, 15-deoxo-30-hydroxyeucosterol 3-O-alpha-L
      rhamnopyranosyl-(1-->2)-[(beta-D-glucopyranosyl-(1-->3)]-beta-D-glucopyranosyl-(1
      ->2)-alpha-L-arabinopyranosyl-(1-->6)-beta-D-glucopyranoside (scillanoside L-1,
      1) and 3beta,31-dihydroxy-17alpha,23-epoxy-5alpha-lanost-8-en-23,26-olactone 3-O
      alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->3)]-beta-D
      glucopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->6)-beta-D-glucopyranoside
      (scillanoside L-2, 2), were isolated from the bulbs of Scilla scilloides,
      together with four that were known (3-6), have been isolated from the bulbs of
      Scilla scilloides. The structures of the new compounds were determined on the
      basis of spectroscopic and chromatographic methods, and some chemical
      transformations were discussed. Amongst the isolated compounds, 3 showed the most
      significant cytotoxicity against tumor cells tested several types with ED(50)
      value of 1.53-3.06 nM. In vivo experiments, 3 apparently increased the life span
      of mice bearing Sarcoma 180 tumor cell with T/C value of 239% at dose of 3 mg/kg.

PMID- 12237545
TI  - Seven germacranolides, eupaglehnins A, B, C, D, E, and F, and 2alpha
      acetoxyepitulipinolide from Eupatorium glehni.
AB  - Four new germacrane-type sesquiterpenoids with unsaturated acids as esters at the
      8-position, two chlorine atom-containing lactones, 2alpha-acetoxyepitulipinolide,
      and 12 previously known compounds have been isolated from the MeOH extract of
      Eupatorium glehni (Compositae) and their structures have been determined on the
      basis of spectral data analyses.

PMID- 12237546
TI  - The influence of ligand side chain on the enantioselectivity of Lewis acid
      catalyzed Diels-Alder reactions.
AB  - The enantioselective Lewis acid-catalyzed Diels-Alder reaction of 3-(2-propenoyl)
      1,3-oxazolidin-2-one 8 with cyclopentadiene was examined using a series of chiral
      mox ligands 2-6, deferring in the side chain at 2-position of the chiral
      oxazoline and in the nature of the substituent at the chiral center (4-position)
      of the oxazoline ring, and a combination of N-[(1R)-2-chloro-1-phenylethyl]-2
      [(4R)-4-phenyl-4,5-dihydrooxazol-2-yl]butyramide 2-MgI(2)-I(2) was the most
      efficient catalyst.

PMID- 12237547
TI  - Removal of fine powders from film surface. I. Effect of electrostatic force on
      the removal efficiency.
AB  - A novel fine particle removal system composed of a corona-discharge neutralizer,
      a pulse-jet air unit and an image processing system has been developed. First of
      all, adhesion force between particle and film was directly measured and effect of
      electrostatic force on the adhesion force was calculated experimentally and
      theoretically. The electrostatic force was found to be significant, leading to
      the suggestion that the countermeasure for the electrostatic force was required
      to effectively remove fine particles. This system was then applied to the removal
      of fine particles from surface of a gelatin film used for conventional capsule
      material. The number of particles removed by the system was calculated by an
      image processing system and number base removal efficiency was computed with and
      without the elimination of electrostatic charge by the neutralizer. It was found
      that the difference between the removal efficiency of particles with elimination
      of electrostatic charge and that of without the elimination showed linear
      relationship with the electrostatic adhesion force. The data confirmed the
      necessity of electrostatic charge elimination for the effective removal of fine
      particles.

PMID- 12237548
TI  - Removal of fine powders from film surface. II. Effect of operating parameters on
      the removal efficiency.
AB  - In the previous paper, a novel fine particle removal system composed of a corona
      discharge neutralizer, a pulse-jet air unit and an image processing system has
      been developed and applied to the removal of fine particles from film surface. We
      have calculated the van der Waals and electrostatic forces between particle and
      film and then reported that the electrostatic force influenced the adhesion
      characteristics significantly and thus the elimination of electrostatic charge
      should be necessary for the effective removal of fine particles. In this paper,
      we have modified the corona-discharge neutralizer for getting much better removal
      performance. The effect of operating parameters on the removal efficiency was
      investigated experimentally. The ratio of fine particle remained on the film
      surface after removal experiment as a function of particle size was measured. It
      was found that fine particles smaller than 15 microm, which were impossible to
      remove by other conventional techniques, could be almost completely removed. This
      method is anticipated to be used in the capsule filling, film packaging and
      tabletting processes for prevention of stain on lens of video automatic
      inspection machines, unpredictable movement of electronic devices, and
      deteriorates of product quality.

PMID- 12237549
TI  - New C(19)-diterpenoid alkaloids from the roots of Delphinium potaninii var.
      jiufengshanense.
AB  - From the roots of Delphinium potaninii var. jiufengshanense, two new lycoctonine
      type C(19)-diterpenoid alkaloids called jiufengdine (1) and jiufengtine (4) have
      been isolated. The structures of the new alkaloids (1, 4) were established by 1D
      and 2D NMR spectra.

PMID- 12237550
TI  - Flavonol triglycosides from the leaves of Hammada scoparia (POMEL) ILJIN.
AB  - A new flavonol triglycoside, isorhamnetin 3-O-beta-D-xylopyranosyl-(1""-->3)
      alpha-L-rhamnopyranosyl-(1'''-->6")-beta-D-galactopyranoside, has been isolated
      from the leaves of Hammada scoparia together with two known compounds,
      isorhamnetin 3-O-beta-D-apiofuranosyl-(1'''-->2")[alpha-L-rhamnopyranosyl-(1""-
      >6")]-beta-D-galactopyranoside and isorhamnetin 3-O-alpha-L-rhamnopyranosyl-(1'''
      ->2")[alpha-L-rhamnopyranosyl-(1""-->6")]-beta-D-galactopyranoside. The
      structures were determined by spectroscopic methods.

PMID- 12237551
TI  - Two new 5-deoxyflavones from Albizia odoratissima.
AB  - Two new 5-deoxyflavones, 7,8-dimethoxy-3',4'-methylenedioxyflavone (1) and
      7,2',4'-trimethoxyflavone (2) together with a known flavone, 7,4'-dimethoxy-3'
      hydroxyflavone (3) were isolated from the rootbark of Albizia odoratissima. The
      structures of these new compounds were elucidated by electrospray ionization mass
      spectrometry (ESI-MS) and 1D and 2D-NMR spectral studies including (1)H-(1)H
      correlation spectroscopy (COSY), heteronuclear single quantum coherence (HSQC),
      heteronuclear multiple bond connectivity (HMBC) and nuclear Overhauser
      enhancement spectroscopy (NOESY).

PMID- 12237552
TI  - Fern constituents: triterpenoids from Adiantum capillus-veneris.
AB  - Two new migrated hopane triterpenoids, viz. 4alpha-hydroxyfilican-3-one and fern
      9(11)-en-12beta-ol, and olean-18-en-3-one and olean-12-en-3-one as the first
      example of oleanane compounds from Adiantum ferns were isolated along with many
      other known triterpenoids from Adiantum capillus-veneris of China and Egypt.
      Their structures were elucidated by spectroscopic analyses.

PMID- 12237553
TI  - Sulfenamide catalyzed oxidation of alcohols to the corresponding carbonyl
      compounds with anhydrous chloramine-T.
AB  - N-tert-Butylbenzenesulfenamide (1) catalyzed oxidation of various alcohols with
      stoichiometric amount of anhydrous chloramines-T (2) proceeded smoothly at room
      temperature to afford the corresponding carbonyl compounds in good yields.

PMID- 12237554
TI  - N-substituted hydroxyureas as urease inhibitors.
AB  - In order to seek a urease inhibitor more potent than hydroxyurea (1), its alkyl-
      or phenyl-substituted derivatives were synthesized and evaluated for their effect
      on the jack bean urease. Of 16 compounds tested, m-methyl- (10) and m-methoxy
      phenyl substituted hydroxyurea (13) showed the most potent inhibitory activities
      against the enzyme.

PMID- 12237555
TI  - Cyclodextrin-mediated deacylation of amino acid esters with marked
      stereoselectivity.
AB  - With respect to the hydrolysis (deacylation) of Z-D(L)-amino acid esters (N
      (benzyloxycarbonyl)-D(L)-amino acid p-nitrophenyl esters) mediated by alpha-,
      beta- and gamma-cyclodextrins (CyDs), a remarkably high enantioselectivity
      (L/D=9.0) was observed for the deacylation of Ala substrate with gamma-CyD. The
      kinetic results on the basis of the Michaelis-Menten principle indicate that the
      enantioselectivity should be mainly originated in the deacylation process of
      substrates following the formation of gamma-CyD-substrate (1 : 1) complexes. The
      computer modeling (molecular mechanics) studies on the inclusion complexes are
      also described.

PMID- 12237556
TI  - New biologically active marine sesquiterpenoid and steroid from the okinawan
      sponge of the genus Axinyssa.
AB  - A new bisabolane-type sesquiterpenoid, (E)-3-isocyanobisabolane-7,10-diene (1),
      and a new epidioxyergostane-type steroid, 9(11)-dehydroaxinysterol (2), were
      isolated from the Okinawan sponge of the genus Axinyssa. Their structures were
      elucidated based on the results of spectroscopic analysis and chemical
      conversion. Epidioxysterol 2 was found to show significant growth inhibitory
      effects against human cancer cell lines.

PMID- 12237557
TI  - Cussosaponins A-E, triterpene saponins from the leaves of Cussonia racemosa, a
      Malagasy endemic plant.
AB  - Five new triterpene saponins, cussosaponins A (2), B (3), C (4), D (5), and E
      (6), were isolated from the dried leaves of Cussonia racemosa BAKER. The
      structures of these new compounds were deduced on the basis of chemical and
      spectroscopic evidence.

PMID- 12237558
TI  - Supercritical fluid extraction and liquid chromatography-electrospray mass
      analysis of vinblastine from Catharanthus roseus.
AB  - Supercritical fluid extraction using carbon dioxide modified with methanol,
      methanol-diethylamine, or methanol-triethylamine was used to extract vinblastine
      from the aerial portions of Catharanthus roseus. An HPLC-electrospray ionization
      (ESI)/MS analysis method was also developed to quantify the alkaloids in these
      extracts. Of the supercritical solvents evaluated, carbon dioxide-methanol
      triethylamine (80 : 18 : 2) at 80 degrees C and 34.0 MPa greatly improved the
      supercritical fluid extraction (SFE) yield of vinblastine by as much as 76.4%
      over methanol extraction, while the other solvent conditions extracted the
      compound at yields less than 25% that of a methanol extraction. These results
      were confirmed by the robust HPLC-ESI/MS analytical method developed in this
      study.

PMID- 12237559
TI  - Two new cinnamic acid esters from Marine brown alga Spatoglossum variabile.
AB  - Two new natural products, n-butyl and isopropyl 3,5-dimethoxy-4-hydroxycinnamate
      were isolated from Spatoglossum variabile. Three known compounds, methyl 3,4,5
      trihydroxybenzoate, 2-deoxyinosine and 9-beta-(D-ribofuranosyl)adenine were
      isolated for the first time from the methanolic extracts of this alga. The
      structure elucidations of the new compounds were carried out with the help of
      modern spectroscopic techniques.

PMID- 12237560
TI  - Stereoselective synthesis of tetrasubstituted (Z)-alkenes from aryl alkyl ketones
      utilizing the Horner-Wadsworth-Emmons reaction.
AB  - Tetrasubstituted (Z)-alkenes were readily prepared through the Horner-Wadsworth
      Emmons reactions of methyl 2-[bis(2,2,2-trifluoroethyl)phosphono]propionate with
      aryl alkyl ketones by employing Sn(OSO(2)CF(3))(2) and N-ethylpiperidine.

PMID- 12237561
TI  - Isolation and structure elucidation of two new alkaloids, pandamarilactonine-C
      and -D, from Pandanus amaryllifolius and revision of relative stereochemistry of
      pandamarilactonine-A and -B by total synthesis.
AB  - Two new pyrrolidine alkaloids, pandamarilactonine-C and -D, were isolated from
      Pandanus amaryllifolius. Based on the total synthesis of pandamarilactonine-C and
      its related alkaloid, pandamarilactonine-A, the relative stereochemistry of
      pandamarilactonine-A and -B, which was previously proposed by spectroscopic
      analysis, was revised.

PMID- 12237562
TI  - Aging, articular cartilage chondrocyte senescence and osteoarthritis.
AB  - The incidence of osteoarthritis (OA), the disease characterized by joint pain and
      loss of joint form and function due to articular cartilage degeneration, is
      directly correlated with age. The strong association between age and increasing
      incidence of osteoarthritis (OA) marks OA as an age related disease. Yet, like
      many other age related diseases, OA is not an inevitable consequence of aging;
      instead, aging increases the risk of OA. Articular cartilage aging changes that
      may lead to articular cartilage degeneration include fraying and softening of the
      articular surface, decreased size and aggregation of proteoglycan aggrecans and
      loss of matrix tensile strength and stiffness. These changes most likely are the
      result of an age related decrease in the ability of chondrocytes to maintain and
      repair the tissue manifested by decreased mitotic and synthetic activity,
      decreased responsiveness to anabolic growth factors and synthesis of smaller less
      uniform aggrecans and less functional link proteins. Our recent work suggests
      that progressive chondrocyte senescence marked by expression of the senescence
      associated enzyme beta-galactosidase, erosion of chondrocyte telomere length and
      mitochondrial degeneration due to oxidative damage causes the age related loss of
      chondrocyte function. New efforts to prevent the development and progression of
      OA might include strategies that slow the progression of chondrocyte senescence
      or replace senescent cells.

PMID- 12237563
TI  - Molecular mechanisms and therapeutics of the deficit in specific force in ageing
      skeletal muscle.
AB  - The age-related impairment in muscle force is only partially explained by the
      loss of muscle mass. The loss both in specific and absolute forces contributes to
      the muscle weakness measured in the elderly and in animal models of ageing.
      Successful interventions aimed at preventing age-associated functional deficits
      will require a better insight into the mechanisms underlying the decline in
      muscle-specific force. The present review article is focused on recent evidence
      supporting excitation-contraction uncoupling as a key factor underlying fast and
      slow muscle fiber impairment with ageing. The molecular, functional and
      structural factors supporting this theory and counteracting measures such as
      insulin-like growth factor 1 transgenic overexpression are discussed.

PMID- 12237564
TI  - Age-related changes in Type 1 and Type 2 cytokine production in humans.
AB  - Although aging is accompanied by several changes in immune function, altered T
      cell function represents the most consistent and dramatic change. Since cytokines
      modulate the immune response, it has been postulated that these age-associated
      changes in T cell function may be due to alterations in cytokine production. Data
      from murine studies generally support an age-related shift from a Th1-like (IL-2,
      IFN-gamma) to a Th2-like (IL-4, IL-6, IL-10) cytokine response; however, whether
      or not such an age-related shift to a Type 2 cytokine response occurs in humans
      is not certain. This review of over 60 studies in humans, in which Type 1 and
      Type 2 cytokines were evaluated either alone or together, suggests that age
      associated changes in cytokine production are inconsistent. Further, these age
      associated changes in cytokine production do not always induce a shift to a Type
      2 cytokine response. Importantly, these studies highlight that the stimulus used
      to induce cytokines influences both the level and pattern of immune response.
      Additional comprehensive evaluations in human studies are both critical and
      necessary to clearly identify the impact of altered cytokine production on age
      related changes in immune function.

PMID- 12237565
TI  - Effect of BCL-2 down-regulation on cellular life span.
AB  - Reactive oxygen species (ROS) are toxic for cells. BCL-2 is known as the anti
      death protein and acts as an antioxidant. When the BCL-2 level of normal
      fibroblasts was suppressed by antisense bcl-2 oligodeoxynucleotide or antisense
      bcl-2 RNA expression, the life span of the culture was shortened by about 11
      population doublings (approx. 15% of the total life span) in comparison to the
      control culture. Since about twice as many cell deaths were observed in the
      antisense culture than in the vector culture, the life span shortening was
      probably caused by ROS-induced death. Acceleration of telomere shortening was not
      evident in the antisense culture. Other BCL-2 family proteins showed no
      significant change in expression. Cell death was suppressed by N-acetyl-L
      cysteine, an antioxidant, suggesting that ROS were the major cause of cell death.
      In conclusion, reduction of BCL-2 makes cells more sensitive to death induced by
      ROS and leads to shortening of the culture's life span.

PMID- 12237566
TI  - Fecundity and life span in transgenic Drosophila melanogaster overexpressing
      hsp70.
AB  - In the present study, we investigated the effect of hsp70 overexpression on some
      life history components in transgenic fruit flies. We measured life span in mated
      flies and fecundity in flies subjected or not subjected to a heat shock inducing
      hsp70. Heat shock increased life span of the parental line, but not of the
      transgenic lines. Genetic manipulation of the flies altered their fecundity, but
      the heat shock had no effect on fecundity. To conclude, we have observed some
      costs of genetic manipulation by itself on life span and fecundity. However, the
      overexpression of the hsp70 extra copies by the exposure to heat did not alter
      the studied variables.

PMID- 12237567
TI  - Accumulation of insoluble protein and aging.
AB  - It is proposed that biological aging mainly depends on a deleterious accumulation
      of insoluble inert protein that has escaped physiological proteolytic
      degradation. Intracellularly, a three-dimensional network of polypeptide chains
      may exclude macromolecular structures and organelles from part of the cytosolic
      water. In this way vital intracellular transport mechanisms may be obstructed,
      providing a rationale to several observations linked to aging.

PMID- 12237568
TI  - A global view of the causes of ageing: an interview with Robin Holliday.

PMID- 12237590
TI  - Chickenpox and the geniculate ganglion: facial nerve palsy, Ramsay Hunt syndrome
      and acyclovir treatment.
AB  - Facial nerve palsy has long been considered to have an infectious etiology.
      Recent diagnostic analyses in children and adults have provided convincing
      evidence that reactivation of varicella-zoster virus (VZV), sometimes during
      infectious mononucleosis, can lead to cranial nerve VII palsy. The site of
      reactivation from latency is the geniculate ganglion. Virus most likely enters
      the ganglion during chickenpox, via the sensory branches of the facial nerve
      located on the ear and tongue. Retrospective reviews suggest that patients with
      VZV-related facial nerve palsy have poorer outcomes than other cases of Bell's
      palsy. Therefore treatment with acyclovir is suggested when VZV reactivation i
      slikely.

PMID- 12237591
TI  - Seroepidemiology of hepatitis A antibodies among children's hospital staff.
AB  - BACKGROUND: With improved socioeconomic conditions, adults are more frequently
      seronegative for hepatitis A virus (HAV) and therefore susceptible to infection.
      A safe and efficacious active HAV vaccine has been developed and licensed. The
      general recommendation is to vaccinate populations at increased occupational
      exposure to HAV. AIM: To determine the seroprevalence of HAV antibodies among
      children's hospital employees and to correlate seropositivity with demographic
      and occupational variables as a basis for formulating vaccine recommendations.
      METHODS: The staff of a tertiary pediatric medical center participated by
      answering a structured questionnaire on demographic and occupational data and by
      donating venous blood for determining HAV antibodies by an enzyme immunoassay.
      Univariate and multivariate analyses were conducted to identify variables
      associated with HAV seropositivity. RESULTS: HAV antibodies were found in 48.3%
      of the 499 employees studied, being lowest in pediatricians (38.7%), and
      increased with years of work at the hospital, job percentage and contact with
      pediatric patients. However, multivariate analysis showed that only the
      sociodemographic variables (age and crowding during childhood) were independently
      and significantly associated with seropositivity. CONCLUSIONS: HAV seropositivity
      was associated mainly with sociodemographic variables. Most children's hospital
      employees, especially pediatricians and other young (<40 years) employees, are
      seronegative and therefore susceptible to HAV. Vaccination of the high risk
      groups should be considered.

PMID- 12237592
TI  - Foodborne disease outbreaks in United States schools.
AB  - BACKGROUND: The objective of this study was to describe the epidemiology of
      foodborne disease outbreaks in schools and to identify where preventive measures
      could be targeted. METHODS: Reports by state and local health departments of
      foodborne disease outbreaks occurring in primary and secondary schools, colleges
      and universities from January 1, 1973, through December 31, 1997, were reviewed.
      Data from ill persons identified through foodborne outbreak investigations and
      subsequently reported to the Centers for Disease Control and Prevention in the
      Foodborne Outbreak Surveillance System were examined. The number and size of
      foodborne disease outbreaks, as well as the etiologic agents, food vehicles of
      transmission, site of food preparation and contributing factors associated with
      outbreaks were also examined. RESULTS: From 1973 through 1997, states and local
      health departments reported 604 outbreaks of foodborne disease in schools. The
      median number of school outbreaks annually was 25 (range, 9 to 44). In 60% of the
      outbreaks an etiology was not determined, and in 45% a specific food vehicle of
      transmission was not determined. Salmonella was the most commonly identified
      pathogen, accounting for 36% of outbreak reports with a known etiology. Specific
      food vehicles of transmission were epidemiologically identified in 333 (55%) of
      the 604 outbreaks. The most commonly implicated vehicles were foods containing
      poultry (18.6%), salads (6.0%), Mexican-style food (6.0%), beef (5.7%) and dairy
      products excluding ice cream (5.0%). The most commonly reported food preparation
      practices that contributed to these school-related outbreaks were improper food
      storage and holding temperatures and food contaminated by a food handler.
      CONCLUSIONS: Strengthening food safety measures in schools would better protect
      students and school staff from outbreaks of foodborne illness. Infection control
      policies, such as training and certification of food handlers in the proper
      storage and cooking of foods, meticulous hand washing and paid sick leave for
      food handlers with gastroenteritis, could make meals safer for American students.

PMID- 12237593
TI  - Respiratory syncytial virus-coded pediatric hospitalizations, 1997 to 1999.
AB  - BACKGROUND: The recent number and rate of infant hospitalizations with a
      respiratory syncytial virus (RSV)-coded diagnosis have not been published.
      METHODS: Retrospective data analysis. National Hospital Discharge Survey data for
      1997 to 1999 were analyzed for discharges of infants < 1 year old with an RSV
      coded diagnosis (ICD-9-CM 466.11, 480.1, 079.6). Hospitalization rates were
      estimated with annual midyear Census data. RESULTS: RSV bronchiolitis was the
      leading primary diagnosis annually for all infants hospitalized for any reason.
      Between 1997 and 1999, 297 684 RSV-coded discharges of infants with an RSV-coded
      diagnosis occurred. The associated hospitalization rate was 25.2 per 1000
      infants. RSV-coded discharges peaked in February. CONCLUSION: RSV bronchiolitis
      was the leading cause of hospital admissions of infants younger than age 1 year
      for any reason between 1997 and 1999.

PMID- 12237594
TI  - Treatment of cerebrospinal fluid shunt infections: a decision analysis.
AB  - BACKGROUND: Cerebrospinal fluid shunts transfer cerebrospinal fluid (CSF) from
      the lateral ventricles in the brain to the peritoneum (ventriculoperitoneal
      shunt) or the right atrium (ventriculoatrial shunt) via subcutaneous Silastic
      tubing. As with any implanted foreign body, infection is a serious complication.
      Although there are several therapeutic modalities currently used for the
      treatment of shunt infections, controversy remains as to which is best given that
      there has been only one randomized trial comparing their effectiveness.
      OBJECTIVE: To determine which treatment modality is most effective by using
      decision analysis to compare three approaches with regard to cure rate, morbidity
      and mortality. METHODS: We constructed a decision tree to map out the different
      treatment modalities and assigned probability values obtained from previously
      published studies. A utility value was assigned to each treatment outcome,
      ranging from 0 to 1.0, with a higher score indicating a more favorable outcome.
      Calculations were performed using Decision Analysis TreeAge computer software.
      RESULTS: The removal of an infected shunt with establishment of external
      ventricular drainage or ventricular taps and administration of antibiotics leads
      to the highest expected value, 0.86. Removal of an infected shunt followed by
      immediate replacement and administration of antibiotics is less effective, with
      an expected value of 0.76. The use of antibiotics alone results in the lowest
      expected value, 0.61. Sensitivity analysis showed the above findings to be robust
      with respect to clinically relevant changes for the baseline probabilities and
      utility values. CONCLUSION: A protocol of shunt removal, external ventricular
      drainage placement or ventricular taps and antibiotics, followed by creation of a
      new shunt when CSF sterility is achieved, is the most effective method of
      treatment for CSF shunt infection.

PMID- 12237595
TI  - Evaluation of the role of respiratory viruses in acute myringitis in children
      less than two years of age.
AB  - BACKGROUND: The etiology of acute myringitis remains controversial although it is
      usually encountered in connection with acute otitis media (AOM). In most cases of
      acute myringitis a bacterial pathogen has been detected in the middle ear fluid,
      but the role of respiratory viruses has remained unclear. Our objective was to
      investigate the etiologic role of viruses in the pathogenesis of acute bullous
      and hemorrhagic myringitis in children <2 years of age. METHODS: A prospective
      longitudinal cohort study of 2028 children ages 7 to 24 months in primary care in
      the Finnish Otitis Media Vaccine Trial. Nasopharyngeal aspirate (NPA) and middle
      ear fluid (MEF) samples taken at the time of the diagnosis were examined by a
      time-resolved fluoroimmunoassay for antigen detection of adenoviruses; influenza
      viruses A and B; parainfluenza viruses 1, 2 and 3; and respiratory syncytial
      virus and by reverse transcription polymerase chain reaction for human rhinovirus
      and human enterovirus. RESULTS: Eighty-two children with bullous myringitis and
      37 children with hemorrhagic myringitis were diagnosed during the 18-month follow
      up period. In bullous myringitis a respiratory virus was detected in 70% of NPA
      samples and in 27% of MEF samples. In hemorrhagic myringitis 57% of NPA samples
      and 28% of MEF samples were virus-positive. The viral distribution was similar to
      that of AOM (virus positive 64% of NPA and 37% of MEF). CONCLUSIONS: We could not
      confirm any specific respiratory virus to be the etiologic agent in acute
      myringitis. The etiology of acute myringitis is similar to that of AOM in
      children <2 years of age.

PMID- 12237596
TI  - Dynamics of pneumococcal nasopharyngeal carriage in children with nonresponsive
      acute otitis media treated with two regimens of intramuscular ceftriaxone.
AB  - BACKGROUND: A 3-day intramuscular ceftriaxone regimen was superior to a 1-day
      regimen in the treatment of nonresponsive acute otitis media caused by resistant
      Streptococcus pneumoniae. However, the effect of various regimens of
      intramuscular cefriaxone on the nasopharyngeal carriage of S. pneumoniae and
      especially that of resistant strains during and after therapy has not been
      thoughtfully studied. OBJECTIVES: To compare the effect of one dose and three
      dose intramuscular ceftriaxone regimens on the nasopharyngeal carriage of S.
      pneumoniae in patients with nonresponsive acute otitis media treated with these
      two regimens and to document the dynamics of nasopharyngeal colonization with S.
      pneumoniae during and after completion of these two therapeutic regimens.
      PATIENTS AND METHODS: In a prospective study performed during January, 1998,
      through September, 1999, 170 evaluable patients ages 3 to 36 months with
      nonresponsive acute otitis media were randomized to receive the 1 (n = 83)- or 3
      (n = 87)-day intramuscular ceftriaxone regimen (50 mg/kg/day), respectively.
      Nasopharyngeal cultures for S. pneumoniae were obtained on Days 1, 4 to 5, 11 to
      14 and 28 to 30. Susceptibility of S. pneumoniae to penicillin and ceftriaxone
      was determined by E-test. RESULTS: On Day 1 nasopharyngeal S. pneumoniae carriage
      was found in 108 (64%) patients, 54 in each treatment group. Forty-seven of 54
      (87%) and 9 of 54 (17%) S. pneumoniae isolates from the one dose group were
      nonsusceptible to penicillin and ceftriaxone, respectively; the respective values
      in the three dose group were 49 of 54 (91%) and 8 of 54 (15%). On Days 4 and 5
      negative nasopharyngeal cultures were achieved in 43 of 83 (52%) and 70 of 87
      (80%) cases from the one dose and three dose group, respectively (P < 0.001).
      Eradication of penicillin-nonsusceptible S. pneumoniae was achieved on Day 4 to 5
      in 18 of 49 (37%) and 39 of 49 (80%) organisms isolated from the one dose and
      three dose groups, respectively (P < 0.001). Nasopharyngeal S. pneumoniae
      carriage among evaluable patients on Days 11 to 14 and Days 28 to 30 was 43 of 69
      (62%) and 31 of 45 (69%) for the one dose group and 42 of 73 (58%) and 31 of 50
      (62%) for the three dose group, respectively (P not significant). A decrease was
      observed during the study period in the proportion of highly penicillin-resistant
      S. pneumoniae isolated in the three dose group compared with the one dose group
      (30, 24, 17 and 13% vs. 30, 27, 19 and 26% at Days 1, 4 to 5, 11 to 14 and 28 to
      30, respectively; P = 0.05). CONCLUSIONS: A marked reduction in the carriage of
      penicillin-nonsusceptible S. pneumoniae (including highly penicillin-resistant
      organisms) was achieved on Days 4 to 5 of therapy with both ceftriaxone regimens.
      The 3-day intramuscular ceftriaxone regimen was significantly superior to the 1
      day regimen in the reduction of carriage during the treatment period. The
      reduction of overall S. pneumoniae nasopharyngeal carriage by both ceftriaxone
      regimens was a short-lived phenomenon followed by rapid recolonization of the
      nasopharynx.

PMID- 12237597
TI  - Response to changes in antiretroviral therapy after genotyping in human
      immunodeficiency virus-infected children.
AB  - BACKGROUND: HIV genotyping has been beneficial when choosing salvage regimens in
      adults failing highly active antiretroviral therapy (HAART). Our objectives were
      to evaluate the usefulness of genotyping in HIVinfected children failing HAART
      and to determine whether the presence of resistance mutations was associated with
      previous antiretroviral therapy. METHODS: We followed the progress of pediatric
      patients who had HIV genotyping performed after HAART failure. Charts were
      reviewed at 3-month intervals for 1 year after genotyping for changes in viral
      load and CD4+ cell percentage. Patients whose antiretroviral therapy was changed
      after genotyping were compared with those whose medications were not changed. We
      also compared the proportion of patients with genotypic mutations according to
      antiretroviral exposure at time of genotyping. RESULTS: Eighteen pediatric
      patients were eligible for inclusion. None of 10 patients who had antiretroviral
      therapy changed after genotyping had a decrease in viral load atmonths after
      genotyping. One of 8 patients who had no changes in antiretroviral therapy had a
      sustained decrease in viral load at 12 months. Two-thirds of patients had
      resistance mutations to antiretrovirals without prior exposure to that drug.
      CONCLUSIONS: This study did not demonstrate substantial clinical benefit to HIV
      genotyping in antiretroviral agent-experienced pediatric patients with high viral
      loads. These results contrast with favorable short term clinical and virologic
      responses to therapeutic changes after genotyping in HIV-infected adults.
      However, medication history alone does not appear to be an adequate alternative
      to genotyping in choosing salvage regimens in antiretroviral agent-experienced
      children.

PMID- 12237598
TI  - Safety and antiretroviral activity of chronic subcutaneous administration of T-20
      in human immunodeficiency virus 1-infected children.
AB  - BACKGROUND: Entry inhibitors, a new class of antiretroviral agents, interfere
      with the attachment, coreceptor interaction or fusion of HIV-1 with host target
      cells. The fusion inhibitor T-20 is the first in this new class, and the present
      study is the first to examine chronic s.c. administration of T-20 to HIV-1
      infected children. METHODS: Fourteen children, 4 to 12 years of age, with
      incompletely suppressed HIV-1 were studied. The median plasma viral load at
      baseline was 26,866 copies/ml (4.4 log10), and the median CD4 count was 523
      cells/mm3. T-20 was administered twice daily by s.c. injection at 30 or 60 mg per
      m2 of body surface area per dose. For 7 days T-20 was added to the patients'
      background antiretroviral regimens; at Day 7 each subject's background therapy
      was changed to a regimen that was predicted to be virologically active, while T
      20 was continued. Results are presented for the first 24 weeks of chronic T-20
      dosing. RESULTS: T-20 was generally well-tolerated. One child discontinued the
      drug because of aversion to injections, but no child discontinued because of
      adverse events. Eleven (79%) of 14 children had local injection site reactions at
      some time during the chronic T-20 dosing. Eleven of 14 subjects achieved the
      protocol-specified milestone of at least a 0.7-log10 reduction in plasma HIV-1
      RNA by Day 7. In 10 subjects (71%) virologic suppression of 1.0 log10 or greater
      was achieved at 24 weeks; 6 subjects (43%) had viral loads <400 copies/ml and 3
      (21%) had fewer than 50 copies/ml at 24 weeks. CONCLUSIONS: These results
      indicate that a 24-week regimen of twice daily s.c. dosing of T-20 in HIV-1
      infected children is safe and tolerable and that it is associated with
      suppression of HIV-1 replication during 24 weeks of administration.

PMID- 12237599
TI  - Efavirenz liquid formulation in human immunodeficiency virus-infected children.
AB  - BACKGROUND: This study determined the safety, pharmacokinetics, antiviral
      activity and immunologic effects of efavirenz liquid formulation, nelfinavir and
      nucleoside reverse transcriptase inhibitors (NRTIs) in HIV-infected children, 3
      to 9 years of age. METHODS: Plasma HIV-1 RNA and lymphocyte subsets were measured
      at various intervals after initiation of therapy. Pharmacokinetic studies were
      performed at Week 2, and doses of efavirenz and nelfinavir were adjusted if area
      under the curve values fell outside specified target ranges. RESULTS: This
      combination of antiretrovirals was well-tolerated. Pharmacokinetic values were
      similar to those observed in a previous study of older children who received
      efavirenz capsules in combination with nelfinavir and NRTIs. After 48 weeks of
      therapy 63% of subjects had plasma HIV RNA levels of <400 copies/ml, and 58% had
      <50 copies/ml in an intent-to-treat analysis. CD4 cell count and percentage rose
      significantly over this time, whereas the number of activated CD8 cells declined.
      CONCLUSIONS: Combination therapy with efavirenz liquid formulation, nelfinavir
      and NRTIs is an attractive treatment option for HIV-infected children >3 years of
      age who are unable to take efavirenz capsules.

PMID- 12237600
TI  - Trends in interventions to reduce perinatal human immunodeficiency virus type 1
      transmission in North Carolina.
AB  - BACKGROUND: Mother-to-child transmission of HIV has decreased in industrialized
      countries because of widespread use of antiretroviral therapy (ART) by HIV
      infected pregnant women and perhaps to increased use of elective cesarean
      section. We evaluated changes in the use of ART and mode of delivery among HIV
      positive pregnant women in North Carolina. METHODS: We reviewed the medical
      records of HIV-exposed infants born in North Carolina between January 1, 1998,
      and December 31, 1999, who were tested for HIV DNA. These results were compared
      with data collected on HIV-exposed infants born from 1993 through 1997. RESULTS:
      The use of combination ART increased from 1.5% in 1996 to 73% in 1999. The most
      common ART was zidovudine/lamivudine (39%) followed by zidovudine-lamivudine
      nelfinavir (34%), although 34 combinations were used. Elective cesarean sections
      in the state increased significantly from 16.5% in the first half of 1998 to
      49.4% in the second half of 1999. Overall transmission rates declined from 24.5%
      in 1993 to an average of 10.6% in 1994 to 1996 (41 of 385) and to 3.5% in 1997 to
      1999 (15 of 428). CONCLUSIONS: Increased use of combination ART and elective
      cesarean section was accompanied by consistently low rates of perinatal
      transmission. However, because perinatal transmission rates were also low among
      women who used combination therapy and had vaginal deliveries, it is difficult to
      determine how much additional benefit cesarean section affords. Most HIV
      transmission occurred among women who lacked prenatal care and did not receive or
      adhere to ART.

PMID- 12237601
TI  - Acute otitis media in infants younger than two months of age: microbiology,
      clinical presentation and therapeutic approach.
AB  - BACKGROUND: Information on the causative agents of acute otitis media (AOM) in
      infants <2 months of age is limited. OBJECTIVES OF THE STUDY: To analyze the
      etiology, pathogen susceptibility patterns, clinical presentation and frequency
      of serious bacterial infections in infants <2 months of age with AOM and to
      determine the relationship between the organisms isolated systemically and those
      isolated from the middle ear fluid in the patients with serious bacterial
      infections in the presence of AOM. METHODS: The medical records of 137 infants <2
      months of age with AOM who underwent tympanocentesis in the emergency room of
      Soroka University Medical Center between January 1, 1995, and May 30, 1999, were
      reviewed. The main variables analyzed included demography, frequency of serious
      bacterial infections, bacteriologic results, susceptibility patterns of the
      pathogens and clinical presentation. RESULTS: Median age was 38.7 +/- 13 days;
      112 of 137 (82%) infants were hospitalized. Six (4%), 27 (20%), 46 (34%) and 58
      (42%) episodes were recorded at age 0 to 2, 3 to 4, 5 to 6 and 7 to 8 weeks,
      respectively. Fever (temperature >38 degrees C) was present in 96 (70%) of the
      cases. Culture-negative (bacterial) meningitis was diagnosed in 3 cases. Blood
      and urine cultures were positive in 1 and 6 infants, respectively. None of the
      afebrile infants developed serious bacterial infection. One hundred twenty-two
      bacterial pathogens were isolated from the middle ear fluid of 109 of 137 (80%)
      patients: Streptococcus pneumoniae in 56 (46%), Haemophilus influenzae in 41
      (34%), group A Streptococcus in 12 (10%), enteric gram-negative bacilli in 9
      (7%), Moraxella catarrhalis in 3 (2%) and Streptococcus faecalis in 1 (1%).
      Eleven (20%) of the 56 S. pneumoniae isolates were nonsusceptible to penicillin.
      Serious bacterial infections were diagnosed in 6 of 137 (4%) patients. Whereas
      blood and urine grew pathogens typical for blood and urinary tract infections,
      the middle ear fluid isolates represented different pathogens usually isolated in
      AOM without any correlation between these 2 groups of pathogens. CONCLUSIONS: (1)
      Most cases of AOM in infants <2 months of age are caused by pathogens similar to
      those causing AOM in older children; (2) antibiotic resistance may already be
      present at early age and should be considered in the empiric treatment of AOM in
      infants <2 months of age; (3) the presence of AOM does not predict a higher risk
      for serious bacterial infections in afebrile and febrile infants <2 months of
      age.

PMID- 12237602
TI  - Role of infected parents in transmission of helicobacter pylori to their
      children.
AB  - AIM: Infected parents, especially infected mothers, may play a key role in
      transmission of Helicobacter pylori within the family. The aim of this population
      based study was to determine the role of parental infection status in
      transmission of H. pylori to the child by taking into consideration the infection
      status of both parents simultaneously. METHODS: Study subjects were a sample of
      preschool children in the city of Ulm, located in Southern Germany, who were
      screened for school fitness between January and July, 1998. The infection status
      of the children was determined by the 13C-urea breath test (UBT). Parental
      infection status was determined by measurement of specific H. pylori IgG
      antibodies in saliva using a modified immunoassay (Milenia H. pylori IgG; DPC,
      Biermann, Germany). The parents provided additional information through a
      standardized questionnaire. RESULTS: We included 305 children ages 5 to 7 years
      (mean age, 5.8 years) and their parents in the analysis. Prevalence of H. pylori
      infection in children by means of UBT was 10.2% [95% confidence interval (CI) 7.0
      14.1%]. The prevalence of infection was 5.1% if the mother showed no salivary
      antibody response against H. pylori and 17.3% if she did. Prevalence of infection
      in children was 6.8% if the father showed no salivary antibody response and 19.1%
      if he did. After adjustment for potential confounders (including infection of the
      spouse), the odds ratio for H. pylori infection of the child was 3.9 (95% CI 1.4
      to 10.6) when the mother was saliva-positive and 2.0 (95% CI 0.8 to 5.3) when the
      father was saliva-positive. CONCLUSION: This study strengthens previous evidence
      that in the population studied infected parents, in particular mothers may play a
      key role in transmission of H. pylori to the child.

PMID- 12237603
TI  - Human immunodeficiency virus drug susceptibility and resistance testing.

PMID- 12237604
TI  - Dietary supplement use for pediatric infections.

PMID- 12237605
TI  - Current concepts on active immunization against respiratory syncytial virus for
      infants and young children.
AB  - Respiratory syncytial virus (RSV) is the most important causative agent of viral
      respiratory tract infections in infants and young children. Passive immunization
      against RSV became available recently, but this does not apply to an effective
      vaccine as a result of dramatic adverse results of immunization with a RSV
      candidate vaccine in the 1960s and the lack of full knowledge of the immune
      response induced by RSV. Nonetheless intensive research during the past two
      decades has resulted in several interesting candidate vaccines, of which some
      have gone through testing in humans. These include the subunit vaccines PFP-1,
      PFP-2, BBG2Na and cold-passaged/temperature-sensitive mutants. The development of
      candidate vaccines against RSV is discussed. Because of questions, uncertainties
      and difficulties with the development of effective vaccines against RSV, it will
      probably be at least another 5 to 10 years before routine immunization against
      RSV becomes available.

PMID- 12237606
TI  - Endocarditis caused by Abiotrophia defectiva in children.
AB  - Abiotrophia defectiva, formerly designated as the member of nutritionally variant
      streptococci, is a part of normal oral flora and may be a cause of culture
      negative endocarditis. We report a case of infective endocarditis caused by A.
      defectiva involving the mitral valve in a 12-year-old girl. She received
      antibiotic treatment for 8 weeks and was symptom-free 6 months after discharge.
      We also reviewed the pediatric cases of nutritionally variant streptococcal
      endocarditis published in the English literature since 1971.

PMID- 12237607
TI  - Incidence of rotavirus diarrhea and intussusception in Hong Kong using
      standardized hospital discharge data.
AB  - Incidence for rotavirus and intussusception was estimated from standardized
      discharge data for all Hong Kong government hospitals (1997 to 1999).
      Intussusception incidence in infants (78 to 100 of 100,000) was relatively high.
      The distinct winter seasonality of rotavirus was not evident for intussusception.
      During the first 5 years of life an estimated 1 child of 28 is admitted with
      rotavirus infection (4% of all medical admissions).

PMID- 12237608
TI  - Tick-borne relapsing fever caused by Borrelia turicatae.
AB  - Tick-borne relapsing fever manifests as relapsing episodes of fever with
      significant morbidity and mortality. We report a case of Borrelia turicatae
      disease in a 13-year-old male youth with outdoor exposures in Texas. After
      multiple clinic visits the diagnosis was made, and treatment was initiated. The
      patient did well without long term sequelae.

PMID- 12237609
TI  - Acute Q fever pericarditis followed by chronic hepatitis in a two-year-old girl.
AB  - Acute Coxiella burnetii infection is most commonly a mild and self-limiting
      disease with fever, pneumonia and hepatitis. Endocarditis is the most frequent
      clinical presentation of chronic infection. We report a 2-year-old child with Q
      fever who presented with acute pericarditis and cardiac tamponade and who
      developed a chronic hepatic infection.

PMID- 12237610
TI  - Chromobacterium violaceum infection in children: a case of fatal septicemia with
      nasopharyngeal abscess and literature review.
AB  - This previously healthy 5-year-old boy initially presented with fever and
      purulent conjunctivitis. The course evolved rapidly into preseptal and facial
      cellulitis, nasopharyngeal abscess and sepsis. Chromobacterium violaceum was
      isolated from conjunctival exudate and blood cultures. He received intravenous
      cefazolin therapy for 2 days, followed by penicillin, oxacillin and netilmicin.
      However, no improvement was noted, and he died on the fifth days of illness.

PMID- 12237611
TI  - Reactivation of varicella-zoster virus in facial palsy associated with infectious
      mononucleosis.
AB  - Facial palsy with infectious mononucleosis, although well-recognized, is rare in
      children, and its pathogenesis is uncertain. To our knowledge there has been no
      previous report describing varicella-zoster virus reactivation as a cause of
      facial palsy associated with infectious mononucleosis. We report such a patient
      in whom serology showed reactivation of varicella-zoster virus.

PMID- 12237612
TI  - Testing infants for human immunodeficiency virus infection.

PMID- 12237613
TI  - Pharmacokinetics of saquinavir in children during long term treatment.

PMID- 12237618
TI  - Tegaserod maleate (Zelnorm) for IBS with constipation.

PMID- 12237619
TI  - Treprostinil (Remodulin) for pulmonary arterial hypertension.

PMID- 12237620
TI  - Echocardiography in search of a cardioembolic source.

PMID- 12237621
TI  - Adverse events that are associated with the selective estrogen receptor modulator
      levormeloxifene in an aborted phase III osteoporosis treatment study.
AB  - OBJECTIVE: Selective estrogen receptor modulators are novel compounds that bind
      to the estrogen receptor and have mixed agonistic and antagonistic activities.
      Recently, an increase in urinary incontinence has been reported with hormone
      replacement therapy use. A decrease in surgical procedures for pelvic floor
      relaxation has been recently reported with raloxifene, a selective estrogen
      receptor modulator that is not uterotropic. Levormeloxifene is a selective
      estrogen receptor modulator that was developed for the purpose of the treatment
      and prevention of postmenopausal osteoporosis. STUDY DESIGN: This was a
      multicentered prospective study of healthy women aged >or=65 years with
      osteoporosis who were randomized to blindly receive placebo or levormeloxifene
      0.5 mg or 1.25 mg daily as part of a planned 3-year osteoporosis treatment study.
      Multiple medical and gynecologic evaluations were performed. Adverse events were
      reported to investigators and coded with the use of World Health Organization
      terminology. This study was halted after 10 months because of the large number of
      gynecologic and other adverse events. RESULTS: Among 2924 women who were studied,
      those women who were treated with levormeloxifene had a marked increase compared
      with placebo in leukorrhea (30% vs 3%), increased endometrial thickness on
      ultrasound scan (19% vs 1%), enlarged uterus (17% vs 3%), uterovaginal prolapse
      (7% vs 2%), urinary incontinence (17% vs 4%), increased micturition frequency (9%
      vs 4%), lower abdominal pain (17% vs 6%), hot flushes (10% vs 3%), and leg cramps
      (6% vs 0.8%). All of these differences were highly statistically significant with
      a probability value of.0001 for each. CONCLUSION: Levormeloxifene results in
      multiple adverse gynecologic and other events in postmenopausal women with
      osteoporosis.

PMID- 12237623
TI  - The pathogenesis of bladder detrusor endometriosis.
AB  - OBJECTIVE: The purpose of this study was to ascertain whether bladder detrusor
      endometriosis originates intraperitoneally in the vesicouterine pouch or
      subperitoneally in the vesicovaginal septum and whether an association exists
      with uterine adenomyosis. STUDY DESIGN: Data were collected on clinical,
      diagnostic, and surgical characteristics of 40 women who were evaluated for
      primary, histologically confirmed, full-thickness detrusor endometriosis.
      RESULTS: In 19 of the 20 women who underwent surgery, the anterouterine pouch was
      partially or totally obliterated with the nodule that was located in the
      posterior wall or dome of the bladder, well above the uterine isthmus, and
      adherent to the anterior uterine wall or fundus. With one exception, pelvic
      ultrasonography, cystoscopy, intravenous pyelography, magnetic resonance imaging,
      and computed tomography identified the lesion cranially with respect to the
      vesicovaginal septum and excluded uterine adenomyosis. CONCLUSION: Vesical
      endometriosis seems to originate from the implantation of regurgitated
      endometrial cells in the anterior cul-de-sac and not to be associated with
      uterine adenomyosis. The metaplasia of subperitoneal mullerian remnants and the
      uterus-vesical adenomyosis extension theories are not compatible with most
      imaging, surgical, and pathologic findings.

PMID- 12237622
TI  - Antitumor effects of the cytotoxic luteinizing hormone-releasing hormone analog
      AN-152 on human endometrial and ovarian cancers xenografted into nude mice.
AB  - OBJECTIVE: Most human endometrial and ovarian cancers express receptors for
      luteinizing hormone- releasing hormone. These receptors can be used for targeted
      chemotherapy with cytotoxic luteinizing hormone-releasing hormone analogs such as
      AN-152, in which doxorubicin is linked to [D-Lys(6)]luteinizing hormone-releasing
      hormone. STUDY DESIGN: The antitumor effects of doxorubicin and AN-152 were
      assessed in vivo in human luteinizing hormone-releasing hormone receptor-positive
      HEC-1B endometrial cancers and NIH:OVCAR-3 ovarian cancers and in the luteinizing
      hormone-releasing hormone receptor-negative SK-OV-3 ovarian line. Nude mice
      bearing these tumors subcutaneously were injected intravenously with saline
      solution (control), AN-152, or doxorubicin at equimolar doses. Luteinizing
      hormone-releasing hormone receptor expression in tumors and specimens of human
      reproductive (n = 5) and nonreproductive (n = 15) normal tissues and in
      hematopoietic stem cells were analyzed with reverse transcriptase-polymerase
      chain reaction and radioligand binding assay. RESULTS: The tumor volumes of
      luteinizing hormone-releasing hormone receptor-positive HEC-1B and NIH:OVCAR-3
      cancers were reduced significantly (P <.001) 1 week after treatment with AN-152
      at 700 nmol/20 g or at 300 nmol/20 g. No toxic side effects were observed.
      Treatment with doxorubicin arrested tumor growth but did not reduce tumor volume.
      Doxorubicin at 700 nmol/20 g caused a high mortality rate and at 300 nmol/20 g
      (8.7 mg/kg) caused a loss of body weight, but no deaths occurred. The growth of
      luteinizing hormone-releasing hormone receptor-negative SK-OV-3 cancers was not
      affected by AN-152. Normal human nonreproductive tissues, hematopoietic stem
      cells, and vaginal tissue did not express luteinizing hormone-releasing hormone
      receptors, but luteinizing hormone-releasing hormone receptors were found in the
      ovary, fallopian tube, cervix, endometrium, and myometrium. CONCLUSION: Targeted
      chemotherapeutic luteinizing hormone-releasing hormone analog AN-152 is more
      effective and less toxic than cytotoxic radical doxorubicin on luteinizing
      hormone-releasing hormone receptor-positive tumors. AN-152 could be considered
      for targeted chemotherapy in patients with ovarian or endometrial cancers.

PMID- 12237624
TI  - Disruption of the endometrial-myometrial border during pregnancy as a risk factor
      for adenomyosis.
AB  - We assessed surgical disruption of the endometrial-myometrial border during
      pregnancy as a risk factor for adenomyosis in a cohort of 1850 women undergoing
      hysterectomy during 1978 to 1981. Women who had 3 or more abortions when sharp
      curettage was common were at increased risk for adenomyosis; women who had
      curettage procedures or cesarean deliveries were not.

PMID- 12237626
TI  - Safety and efficacy of fluoxetine in patients who receive oral contraceptive
      therapy.
AB  - OBJECTIVE: Because many women who receive pharmacologic therapy with
      antidepressants are also prescribed oral contraceptives, it is important to
      assess the risk of clinically significant drug interactions. We reviewed the
      United States fluoxetine clinical trial database, specifically analyzing women
      ages 18 to 45 years, for differences in safety, antidepressant efficacy, and
      unplanned pregnancies that were associated with oral contraceptive use. STUDY
      DESIGN: Data from 17 double-blind, placebo-controlled clinical trials in 1698
      women were analyzed retrospectively. A subgroup of women with oral contraceptive
      use was compared with a subgroup of women with no oral contraceptive use.
      Differences in treatment-emergent adverse events, unplanned pregnancies, and 17
      item Hamilton Depression Scale (HAMD-17) scores were analyzed. RESULTS: The only
      treatment-emergent adverse events that showed a statistically significantly
      different odds ratio for oral contraceptive use versus no oral contraceptive use
      were headache, asthenia, and pain. There was not a statistically significant
      interaction in the incidence of unintended pregnancies (P =.111) or in the
      changes from baseline in HAMDD-17 scores. CONCLUSION: There is no clinical
      evidence that concomitant use of oral contraceptives and fluoxetine affects the
      safety or efficacy of either agent.

PMID- 12237625
TI  - Hysteroscopic transcervical endometrial resection versus thermal destruction for
      menorrhagia: a prospective randomized trial on satisfaction rate.
AB  - OBJECTIVE: The purpose of this study was to compare the satisfaction rate and the
      effectiveness of transcervical hysteroscopic endometrial resection and thermal
      destruction of the endometrium in the treatment of menorrhagia. STUDY DESIGN: A
      prospective randomized trial with 2 years of follow-up was carried out in the
      Department of Gynecology of the University of Naples. Eighty-two patients who
      were affected by menorrhagia that was unresponsive to medical treatment were
      respectively randomized to transcervical hysteroscopic endometrial resection or
      to thermal destruction of the endometrium. Satisfaction rate, operative time,
      discharge time, complication rate, reintervention rate, and resumption of normal
      activity were evaluated in each group. RESULTS: The satisfaction rate was
      significantly higher in the thermal destruction group. Operative time was
      significantly shorter in the thermal destruction group (24 +/- 4 minutes vs 37 +/
      6 minutes). Intraoperative blood loss was significantly lower in the thermal
      destruction group (7.2 +/- 2.8 mL vs 89 +/- 38 mL). Reintervention rates were
      higher in the transcervical hysteroscopic endometrial resection group, although
      postoperative pain was not significantly different between the two groups.
      Discharge time, complication rate, and resumption of normal activity were not
      significantly different between the two groups. CONCLUSION: Thermal destruction
      of the endometrium for the treatment of menorrhagia should be considered an
      effective therapeutic option because of its acceptability among patients, shorter
      operative time, and lower blood loss.

PMID- 12237627
TI  - Twice-weekly transdermal estradiol and vaginal progesterone as continuous
      combined hormone replacement therapy in postmenopausal women: a 1-year
      prospective study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the acceptability and
      endometrial safety of a twice-weekly administration of transdermal estradiol
      (0.05 mg) systems and vaginal progesterone gel (Crinone [Serono, Rome, Italy] 4%,
      45 mg/d) as a continuous combined nonoral hormone replacement therapy regimen.
      STUDY DESIGN: Thirty-five postmenopausal women took part in this 1-year
      prospective observational trial. The bleeding pattern, blood pressure, weight,
      endometrial thickness, and endometrial histologic characteristics of the women
      were monitored. Mean values were compared before and after treatment by paired
      Student t tests. RESULTS: Twenty-six (74.3%) women completed the study and were
      totally amenorrheic. A total of 350 cycles yielded valuable data. Of these, 287
      (82%) cycles were amenorrheic. At month 3, blood pressure and weight decreased
      significantly. At final assessment, endometrial thickness was significantly
      greater than baseline (4.6 +/- 0.9 vs 3.6 +/- 0.9 mm; P <.0005), and histologic
      examination revealed endometrial atrophy in 24 (92.3%) cases and signs of
      decidualization in 2 cases. CONCLUSION: Transdermal estradiol and a twice-weekly
      administration of the vaginal progesterone gel Crinone constitutes a new, viable
      hormone replacement therapy regimen. It represents a practical option for a no
      bleed treatment, ensuring both high endometrial protection and the inherent
      safety linked to administrating physiologic hormones nonorally.

PMID- 12237628
TI  - Antimicrobial components of vaginal fluid.
AB  - OBJECTIVE: We examined the antimicrobial activity and composition of vaginal
      fluid. STUDY DESIGN: Vaginal fluid from preweighed tampons was assayed for pH,
      lactic acid, and antimicrobial polypeptides. The fluid was also fractionated by
      molecular filtration. Antimicrobial activity of whole fluid was determined
      against representative resident and exogenous microbes, and its fractions were
      tested against Escherichia coli. RESULTS: Vaginal fluids (5/5 donors) were
      permissive for Lactobacillus crispatus and vaginalis and Candida albicans, but
      not for Escherichia coli, Streptococcus group B, and Lactobacillus jensenii in
      three of five donors. The antimicrobial activity against E coli was predominantly
      in a <3-kd fraction and correlated with both low pH and high lactic acid content.
      Compared with a matched pH buffer, lactic acid markedly suppressed the growth of
      E coli. Concentrated 2- or 5-fold, the protein-rich fraction was active against E
      coli. CONCLUSION: Vaginal fluid exerts selective antimicrobial activity against
      nonresident bacterial species. The activity is mediated by lactic acid, low pH,
      and antimicrobial polypeptides.

PMID- 12237629
TI  - Prevalence of vulvovaginal candidiasis and susceptibility to fluconazole in
      women.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of vaginal
      colonization by Candida with the use of a rapid detection method, to examine the
      determinants of vaginal candidiasis, and to evaluate susceptibility for
      fluconazole. STUDY DESIGN: Vaginal swabs were collected from unselected women at
      the outpatient clinic of the Department of Obstetrics and Gynecology. A
      differentiation was made between patients with a positive and a negative
      potassium hydroxide examination. RESULTS: Six hundred twelve women were
      recruited, of whom 39 women (6.3%) had clinical candidiasis. The overall rate of
      yeast colonization was 20.1%. Candida albicans was isolated most
      frequently(68.3%), followed by C glabrata (16.3%) and C parapsilosis (8.9%).
      Clinical candidiasis was related positively with the state of estrogen
      impregnation. In vitro susceptibility testing by the National Committee for
      Clinical Laboratory Standards method for fluconazole revealed that 21.1% of the
      isolates were resistant. CONCLUSION: More than 20% of the unselected women were
      colonized with Candida species. Hyperestrogenemia was associated with an
      increased vulvovaginal colonization by Candida. Surprisingly, 21% of the isolates
      was resistant to fluconazole, according to the National Committee for Clinical
      Laboratory Standards method.

PMID- 12237630
TI  - Evaluation of beta1,4-galactosyltransferase as a potential biomarker for the
      detection of subclinical disease after the completion of primary therapy for
      ovarian cancer.
AB  - OBJECTIVE: Approximately 50% of patients with ovarian cancer who have normal CA
      125 levels at the completion of therapy have persistent disease. In an effort to
      improve the ability to detect small volume disease, we have evaluated the
      usefulness of N-acetylglucosamine:beta1,4-galactosyltransferase as a potential
      biomarker for the detection of subclinical disease after the completion of
      primary therapy for ovarian cancer. STUDY DESIGN: The sera of 33 patients with
      stage IIIC epithelial ovarian cancer in complete clinical remission after
      chemotherapy (CA 125 <35 units/mL and negative computed tomography scan) who
      underwent second-look surgery were examined for N-acetylglucosamine:beta1,4
      galactosyltransferase activity. The values were determined from sera that had
      been obtained before primary cytoreductive operation and before second-look
      surgery after the completion of platinum-based chemotherapy. Determinations of
      the levels of CA 125 were performed with the Bayer Immuno ITM CA-125 II assay. N
      acetylglucosamine:beta1,4-galactosyltransferase activity was determined by
      measuring the transfer of galactose from uridine diphosphate- carbon 14-labeled
      galactose to the terminal N-acetylglucosamine residue of a very well-defined
      synthetic acceptor, N-acetylglucosamine:beta1,6GalNAc(alpha)-o-benzyl, which is a
      portion of the core structure of mucin glycoproteins. The cutoff value of N
      acetylglucosamine:beta1,4-galactosyltransferase was determined to be 22,000
      counts/min, based on the analysis of 25 healthy control subjects. Correlation
      between serum CA 125 and N-acetylglucosamine:beta1,4-galactosyltransferase levels
      was determined with the use of the Pearson correlation coefficient. The ability
      of galactosyltransferase to identify small volume disease correctly was also
      evaluated. RESULTS: There was a significant correlation between serum CA 125 and
      N -acetylglucosamine:beta1,4-galactosyltransferase levels before the operation (r
      = 0.57; P =.03) but not before second-look surgery (r = 0.10; P =.57). Thirteen
      patients (39.4%) had residual disease at second-look surgery. Elevated N
      acetylglucosamine:beta-1,4galactosyltransferase activity >22,000 cpm correctly
      identified 10 of these patients (76.9%). The sensitivity, specificity, and
      positive and negative predictive values of N-acetylglucosamine:beta1,4
      galactosyltransferase activity (>22,000 counts/min) for the prediction of
      residual disease at second-look surgery were 77%, 45%, 48%, and 77%,
      respectively. CONCLUSION: Our comparative study of serum CA 125 and N 
      acetylglucosamine:beta1,4-galactosyltransferase levels showed a significant
      correlation between the two tumor markers before the beginning of ovarian cancer
      therapy. This correlation disappeared before second-look surgery because 60% of
      patients with normal serum CA 125 and N-acetylglucosamine:beta1,4
      galactosyltransferase levels. CA 125 antigen appears to be inferior to N 
      acetylglucosamine:beta1,4-galactosyltransferase in the detection of small-volume
      residual disease. N-acetylglucosamine:beta1,4-galactosyltransferase may be useful
      as a biomarker in the monitoring of patients with ovarian cancer when the serum
      CA 125 level is normal. These findings require confirmation in larger studies.

PMID- 12237631
TI  - Urinary tract infections in women with or at risk for human immunodeficiency
      virus infection.
AB  - OBJECTIVE: The purpose of this study was to determine the risk for urinary tract
      infection in women with or at risk for human immunodeficiency virus infection.
      STUDY DESIGN: A prospective study of 871 women who were human immunodeficiency
      virus seropositive and 439 women who were human immunodeficiency virus
      seronegative was conducted, with additional semiannual interviews, human
      immunodeficiency virus serologic evaluation, human immunodeficiency viral load
      determination, T-cell subset test, urinalysis, pregnancy test, and selected
      quantitative urine culture examination. RESULTS: At baseline, 26 women (3.0%) who
      were human immunodeficiency virus seropositive and 14 women (3.2%) who were human
      immunodeficiency virus seronegative women had urinary tract infections(P =.97).
      During 4280 person-years of follow-up, incident urinary tract infections was
      associated significantly with <12 years education (adjusted risk ratio, 1.43; 95%
      CI, 1.01-2.00), public assistance (adjusted risk ratio, 1.70; 95% CI, 1.11-2.60),
      pregnancy (adjusted risk ratio, 3.04; 95% CI, 2.04-4.53), and recent previous
      urinary tract infection (adjusted risk ratio, 1.82; 95% CI, 1.16-2.86), but not
      with human immunodeficiency virus infection. Among women who were human
      immunodeficiency virus seropositive, risk was associated with viral load
      (adjusted risk ratio, per log(10) increase 1.30; 95% CI, 1.03-1.63), but not with
      CD(4+) lymphocyte count. CONCLUSION: Risk for urinary tract infection is not
      associated with human immunodeficiency virus infection but is associated with
      viral load among women who are infected with human immunodeficiency virus.

PMID- 12237632
TI  - Differential characterization of women with vulvar vestibulitis syndrome.
AB  - OBJECTIVE: We differentiated women with vulvar vestibulitis syndrome into
      subgroups on the basis of the time of symptom onset, a history of recurrent
      vulvovaginal candidiasis, and the interleukin-1 receptor antagonist gene
      polymorphism. STUDY DESIGN: One hundred sixty-two consecutive patients with
      strictly defined vulvar vestibulitis syndrome were asked to fill out a
      questionnaire with the assistance of their gynecologist. A buccal sample was
      collected from each subject for the analysis of interleukin-1 receptor antagonist
      gene polymorphism; vaginal and vestibular microbial investigations were
      performed. RESULTS: Symptoms began with the first act of coitus in 20.4% of
      patients. A history of a recurrent Candida vulvovaginal infection was reported in
      42.6% of patients; 25.9% of the patients were positive for the homozygous
      interleukin-1 receptor antagonist 2,2 genotype. Women with primary vulvar
      vestibulitis syndrome differed from women with secondary vulvar vestibulitis
      syndrome; women with primary vulvar vestibulitis syndrome were younger at the
      time of the onset of the symptoms (23.8 vs 31.2 years, P <.0001) and had never
      been pregnant (84.8% vs 61.2%, P <.0001). Women with a history of recurrent
      Candida vulvovaginitis differed from the other subjects by having a higher
      frequency of constant vestibular pain (40.6% vs 20.4%, P =.005), a vaginal
      discharge (79.7% vs 45.2%, P <.0001), and dysuria (62.3% vs 29.0%, P =.0001).
      Women who were homozygous for interleukin-1 receptor antagonist 2,2 genotype had
      an earlier onset of symptoms (26 years) than did women who were allele 1
      homozygotes (31.3 years, P <.05). They also had a shorter duration of symptoms
      (4.1 vs 5.9 years, P <.05) and a higher frequency of allergy (47.6% vs 23.4%, P
      =.002). Human papillomavirus in the vaginal vestibule occurred at a greater
      frequency in women who were homozygous for interleukin-1 receptor antagonist 2,2
      genotype. CONCLUSION: Subgroups of women with vulvar vestibulitis syndrome may be
      differentiated by symptomatic and genetic variables.

PMID- 12237633
TI  - Maternal plasma cellular fibronectin concentrations in normal and preeclamptic
      pregnancies: a longitudinal study for early prediction of preeclampsia.
AB  - OBJECTIVE: The purpose of this study was to examine cellular fibronectin levels
      throughout normotensive and preeclamptic pregnancies and to analyze its
      predictive value for the detection of preeclampsia within the second trimester of
      pregnancy. STUDY DESIGN: Blood samples were collected at 4-week intervals from
      378 healthy, nulliparous women who were recruited before 16 weeks of gestation.
      Preeclampsia developed in 26 patients; 52 normotensive control subjects were
      matched from the same cohort. Plasma samples were assayed for ED-B fibronectin by
      enzyme-linked immunosorbent assay. Trends were compared between groups.
      Predictive values were determined with the use of second trimester assessments.
      RESULTS: In both groups, fibronectin levels rose as pregnancy advanced, but in
      women with preeclampsia, this increase was significantly higher (94.5% vs 31.8%;
      P =.006). Throughout pregnancy, patients with preeclampsia exhibited
      significantly higher fibronectin levels than did control subjects. As early as 9
      to 12 weeks of gestation, a difference was established (preeclampsia, 3.72 +/-
      0.21; control, 2.94 +/- 0.22 microg/mL [mean +/- SEM]; P =.008). The best cutoff
      point and time interval to calculate predictive values were 3.8 microg/mL and 22
      to 26 weeks of gestation, respectively. Sensitivity, specificity, and positive
      and negative predictive values were 73%, 87%, 29%, and 98%, respectively; the
      odds ratio was 16.1 (95% CI, 8.6-30.2). CONCLUSION: In women in whom clinical
      preeclampsia developed, endothelial damage seemed to be present since early
      gestation. Cellular fibronectin levels of >or=3.8 microg/mL within 22 to 26 weeks
      of gestation may help in the early detection of preeclampsia in healthy
      nulliparous women.

PMID- 12237634
TI  - Substance abuse and polyhydramnios.
AB  - OBJECTIVE: Maternal drug use is known to have fetal central nervous system
      depressive effects as manifested by decreased biophysical profile scores. Drug
      effects on the amniotic fluid index (AFI), one variable of the biophysical
      profile, are not well documented. Our objective was to determine the effects of
      maternal drug use on the AFI. STUDY DESIGN: Over an 18-month period from July
      1997 to December 1998, consecutive cases of women with toxicology-proven drug use
      during pregnancy were identified. AFI values and the rate of polyhydramnios in
      substance users were compared with those observed at our institution in more than
      6400 patients undergoing ultrasound testing during the same period as the cases.
      RESULTS: Sixty-three toxicology-positive cases were identified. Although there
      was no significant difference between mean AFI values, the incidence of
      polyhydramnios (AFI >24 cm) was significantly higher in substance users (28.6%)
      than in control patients (3.9%) (P <.005). CONCLUSION: Maternal substance abuse
      is associated with a significantly higher incidence of polyhydramnios and should
      be considered a possible etiologic factor in women with apparent idiopathic
      polyhydramnios.

PMID- 12237635
TI  - No difference in structure between omental small arteries isolated from women
      with preeclampsia, intrauterine growth restriction, and normal pregnancies.
AB  - OBJECTIVE: Our purpose was to investigate whether there were structural
      differences between omental small arteries isolated from women with preeclampsia
      and intrauterine growth restriction and those isolated from women with normal
      pregnancy. STUDY DESIGN: A pressure myograph was used to study omental small
      arteries isolated from women with normal pregnancy and women with preeclampsia
      and intrauterine growth restriction (n = 16, 13, and 8, respectively). With the
      use of a transilluminating system, lumen diameter, wall thickness, wall/lumen
      ratio, distensibility, and the stress-strain relationship were studied through
      pressure ranges of 5 to 100 mm Hg. Arteries were then fixed with glutaraldehyde
      at the predelivery mean arterial pressure and embedded in epoxy resin. One
      micrometer transverse sections were cut for more detailed morphologic
      examination. RESULTS: Wall thickness, lumen diameter, wall/lumen ratio,
      distensibility, and the stress-strain relationship of omental small arteries did
      not differ between patient groups (P >.05; repeated-measures analysis of
      variance). Detailed histologic examination confirmed these findings. CONCLUSIONS:
      Alterations in systemic vascular resistance associated with compromised
      pregnancies are unlikely to result from or produce an alteration in the structure
      of omental small arteries.

PMID- 12237636
TI  - A state-wide assessment of the obstetric, anesthesia, and operative team
      personnel who are available to manage the labors and deliveries and to treat the
      complications of women who attempt vaginal birth after cesarean delivery.
AB  - OBJECTIVE: The purpose of this study was to determine on a state-wide basis the
      range of obstetric, anesthesia, and surgical team personnel who were available
      immediately to manage the labors and deliveries of women who attempted vaginal
      birth after cesarean delivery. Additionally, we tried to determine whether
      hospitals had stopped performing vaginal births after cesarean delivery or made
      changes in their policies regarding vaginal birth after cesarean delivery as a
      result of recent American College of Obstetricians and Gynecologists
      recommendations. STUDY DESIGN: Available immediately was defined as "being
      present in the hospital." All hospitals that provided obstetric care in the State
      of Ohio were surveyed to determine whether an obstetrician with cesarean
      privileges, an anesthesiologist, or an anesthetist capable of independently
      administering anesthesia for a cesarean section, and a surgical team were
      available immediately when women attempted vaginal birth after cesarean delivery.
      The hospitals were also asked whether they had stopped allowing vaginal births
      after cesarean delivery or had made changes in their vaginal birth after cesarean
      delivery policies in response to the recent recommendations of the American
      College of Obstetricians and Gynecologists. Data were computerized and analyzed
      by the chi(2) test. RESULTS: Seventy-seven (93.9%), 35 (100%), and 13 (100%) of
      level I, II, and III hospitals performed vaginal births after cesarean delivery.
      An obstetrician was immediately available in 27.3%, 62.9%, and 100% of level I,
      II, and III institutions, respectively (P <or=.001). Anesthesia availability was
      39%, 100%, and 100% of level I, II, and III institutions, respectively (P
      <or=.001). A surgical team was available in 35.1%, 97.1%, and 100% of level I,
      II, and III hospitals, respectively (P <or=.001). A complete complement was
      available in 15.6%, 62.9%, and 100% of level I, II and III institutions,
      respectively (P <or=.001). Two hospitals had stopped the performance of vaginal
      births after cesarean delivery, and 10 additional hospitals were considering
      stopping the performance of vaginal births after cesarean delivery. Policy
      changes had been adopted in 15 institutions, and 4 other institutions were
      considering changes. CONCLUSION: Most level I and many level II hospitals provide
      less than optimum staffing when women are attempting vaginal birth after cesarean
      delivery. Because vaginal births after cesarean delivery are equally distributed
      among level I, II, and III institutions in this state, many women may be
      attempting vaginal birth after cesarean delivery under less than optimal
      conditions. The data suggest the need for changes in staffing or referral
      patterns to safely meet the Healthy People 2010 goal of increasing the vaginal
      birth after cesarean delivery rate nationally.

PMID- 12237637
TI  - Dose variation that is associated with approximated one-quarter tablet doses of
      misoprostol.
AB  - OBJECTIVE: The purpose of this study was to evaluate dose variation in
      approximated one-quarter tablet misoprostol fragments. STUDY DESIGN: Misoprostol
      100 microg tablets were weighed, separated into two lots, and quartered with a
      razor blade or a pill cutter. Fragments were reweighed, and the misoprostol
      content was determined by high-performance liquid chromatography mass
      spectroscopy. RESULTS: Fragment weights varied more when a pill cutter was used
      (P <.0001). Fewer pill-cutter fragments than razor-cut fragments weighed within
      10% of expected (24% vs 65%, P <.0001). Misoprostol content among the fragments
      that were determined by high-performance liquid chromatography mass spectroscopy
      was 103% +/- 12% of expected (range, 73%-124%). Tablet fragments that weighed
      >or=27.5 mg contained misoprostol in excess of 110% of expected in seven of eight
      fragments, although none from fragments that weighed <or=26.5 mg did. Misoprostol
      was evenly distributed in all fragments that were assayed. CONCLUSION:
      Misoprostol is evenly distributed among tablet fragments. Accurate low-dose
      misoprostol cervical ripening is possible if the tablet fragments are
      individually weighed.

PMID- 12237638
TI  - Folate levels in pregnant women who smoke: an important gene/environment
      interaction.
AB  - OBJECTIVE: The objective of this study was to determine whether serum and red
      blood cell folate levels were decreased in pregnant women who smoke and whether
      total plasma homocysteine levels were elevated. STUDY DESIGN: In this cross
      sectional study, serum folate, red blood cell folate, and homocysteine were
      measured in pregnant first- and early second-trimester pregnant women who smoked
      (case subjects) and pregnant women who did not smoke (control subjects). In
      addition, vitamin B(12), albumin, creatinine, cotinine, and hematocrit levels and
      methylenetetrahydrofolate reductase status were determined and compared between
      groups. RESULTS: Pregnant women who smoked had significantly lower concentrations
      of serum folate (22.7 vs 29.4 nmol/L; P =.001) and lower concentrations of red
      blood cell folate (766 vs 900 nmol/L; P =.038 [not significant]) than pregnant
      women who did not smoke. Dietary folate intake was not significantly different
      between pregnant women who smoked and pregnant women who did not smoke.
      Homocysteine levels were also not significantly different between the groups. For
      each genotype of methylenetetrahydrofolate reductase, lower levels of serum
      folate were observed in pregnant women who smoked, with the lowest folate levels
      seen in homozygous mutant methylenetetrahydrofolate reductase 677TT (18.6 nmol/L
      in pregnant women who smoked vs 24.2 nmol/L in pregnant women who did not smoke).
      CONCLUSION: Both serum folate and red blood cell folate are lower in pregnant
      women who smoked than in pregnant women who did not smoke, although homocysteine
      levels are not significantly different. There is an important gene environment
      interaction between methylenetetrahydrofolate reductase gene activity and tobacco
      exposure on serum folate levels. Lower levels of serum folate may account for the
      higher rate of miscarriage, stillbirth, abruptio placentae, and fetal anomalies
      that are observed in pregnant women who smoke. Pregnant women who smoke may
      benefit from higher doses of folic acid periconceptionally.

PMID- 12237639
TI  - Cerebral perfusion pressure, and not cerebral blood flow, may be the critical
      determinant of intracranial injury in preeclampsia: a new hypothesis.
AB  - OBJECTIVE: The relationship between cerebral perfusion pressure (CPP) and
      cerebral blood flow is unclear in preeclampsia. Our objective was to clarify this
      issue by comparing normal pregnant women to those with mild and severe
      preeclampsia. STUDY DESIGN: Patients with mild (n = 72) and severe (n = 120)
      preeclampsia underwent transcranial Doppler (TCD) imaging of the maternal middle
      cerebral artery (MCA). At the same time, blood pressure was taken with a Dinamap
      monitor (Dinamap; Criticon Inc, Tampa, Fla). CPP, resistance area product (RAP),
      and the cerebral flow index (CFI) were calculated by standard formulas. Data were
      plotted on normative curves for pregnancy (5% and 95%) and compared by chi(2) and
      Mann-Whitney U tests. RESULTS: CFI is usually normal in both severe (75%) and
      mild (72%) cases. If CFI is abnormal in severe cases, it may be either increased
      (14%) or decreased (10%), although in mild cases almost all abnormal CFI (25%) is
      lower than normal. In those cases with low or normal CFI, severe cases are
      associated with a significantly higher CPP, RAP, and MAP than mild cases (P
      <.05), although the CFI is not significantly different. A significant proportion
      of severe cases have high CPP (52%), whereas in mild cases the CPP is almost
      always normal (87%). Overall, in severe cases the RAP is abnormally high,
      although it is within the normal range in mild cases. CONCLUSIONS: One of the
      fundamental differences between mild and severe cases relates to the degree of
      cerebral perfusion pressure that the MCAs are subjected to. Because most
      preeclamptic women, regardless of degree of severity, have a normal CFI, it
      appears that autoregulation is generally intact. Because women with severe cases
      are more prone to cerebral catastrophe than those with mild preeclampsia,
      uncontrolled CPP may cause barotrauma and vessel damage, leading to hypertensive
      encephalopathy and overperfusion injury. Therapeutic strategies that ensure
      reduction of the CPP with maintenance of the CFI seem most likely to prevent the
      cerebral injuries (overperfusion or underperfusion) that cause seizures or death
      in women with preeclampsia.

PMID- 12237640
TI  - Selective reduction of acardiac twin by radiofrequency ablation.
AB  - OBJECTIVE: Acardiac/acephalic twinning is a rare anomaly in which a normal "pump"
      twin perfuses an acardiac twin, which results in twin reversed arterial perfusion
      sequence. A novel technique for selective reduction and obliteration of blood
      flow in the acardiac twin is described. STUDY DESIGN: Thirteen consecutive cases
      of monochorionic twin gestation with twin reversed arterial perfusion sequence
      underwent selective reduction of the abnormal twin with the use of radiofrequency
      ablation. Under direct real-time sonographic guidance, a 3-mm (14-gauge)
      radiofrequency ablation needle was percutaneously inserted through the maternal
      abdominal wall into the intrauterine fetal abdomen at the level of the cord
      insertion site of the acardiac twin. Energy was applied until termination of
      blood flow to the acardiac fetus was documented by Doppler ultrasound scanning.
      RESULTS: All 13 mothers tolerated the procedure without major complications. All
      13 "pump" fetuses have been delivered. Twelve of 13 infants are alive and well.
      The first patient in this series was delivered at 24.4 weeks and the infant
      subsequently died from complications of prematurity. Average gestational age at
      intervention was 20.7 weeks, and the average gestational age at delivery was 36.2
      weeks. CONCLUSION: Radiofrequency ablation is a minimally invasive, percutaneous
      technique that can effectively obliterate blood supply to an acardiac twin to
      preserve and protect the pump twin.

PMID- 12237641
TI  - Beta2- and beta3-adrenoreceptor agonists: human myometrial selectivity and
      effects on umbilical artery tone.
AB  - OBJECTIVE: The purpose of this study was to investigate the functional
      selectivity of the beta(3)-adrenoreceptor agonist BRL 37344 and the beta(2)
      adrenoreceptor agonist ritodrine for their putative receptors in human pregnant
      myometrium in vitro and to examine the possibility that BRL 37344 may exert an
      effect on other beta-adrenoreceptor subtypes. This study also aimed comparatively
      to evaluate the in vitro effects of BRL 37344 and ritodrine on human vascular
      tissue tone. STUDY DESIGN: The effects of BRL 37344 (1 nmol/L-100 micromol/L) and
      ritodrine (1 nmol/L-100 micromol/L) on isometric tension recordings that were
      performed in isolated myometrial strips that were obtained at elective cesarean
      delivery and in human umbilical artery rings that were obtained at term were
      measured. Antagonism of the effects of BRL 37344 and ritodrine in human
      myometrial tissue was investigated with the antagonists butoxamine (1
      micromol/L), propranolol (1 micromol/L), and bupranolol (1 micromol/L). The
      concentrations that produced a 50% maximal effect, the mean maximal inhibition
      that was achieved, and the percentage of contractility that was observed were
      compared. RESULTS: Bupranolol (n = 6), but not butoxamine (n = 6) or propranolol
      (n = 6), antagonized the relaxant effects of BRL 37344 in human pregnant
      myometrium; all three compounds (n = 6, respectively) antagonized the effects of
      ritodrine. At concentrations of >1 micromol/L, ritodrine exerted a significantly
      more potent vasodilatory effect than BRL 37344 on human umbilical artery tone (P
      <.01). CONCLUSION: The relaxant effects of BRL 37344 appear to be mediated solely
      through the beta(3)-adrenoreceptor agonist, although ritodrine may exert an
      effect on beta(1)-, beta(2)-, and beta(3)-adrenoreceptor agonists. This and the
      reduction in vascular tissue effects observed with BRL 37344 suggest that uterine
      beta(3)-adrenoreceptor modulation may provide a novel scientific approach to
      tocolysis with fewer vascular adverse effects.

PMID- 12237642
TI  - Four-year follow-up of women who were diagnosed to have postpartum urinary
      retention.
AB  - OBJECTIVE: The purpose of this study was to evaluate the long-term prevalence of
      urinary incontinence in women with postpartum urinary retention. STUDY DESIGN: A
      telephone interview was conducted by contacting a cohort of 691 women who
      delivered vaginally 4 years ago, of which 101 women had been diagnosed as having
      postpartum urinary retention. A structured telephone interview consisted of 9
      questions on the possible outcomes of postpartum urinary retention. RESULTS: Of
      the original cohort of 691 women, 394 women were contacted. Seventy-three women
      had had postpartum urinary retention, and 321 women had not. In women who had had
      postpartum urinary retention, the prevalence of the outcome variables were
      urinary stress incontinence (28.8%), fecal incontinence (2.7%), frequency
      (39.1%), nocturia (65.2%), urgency (26.1%), urge incontinence (26.1%), and coital
      incontinence (13%). Analyses showed that there was no significant difference
      between women with and without urinary retention. CONCLUSION: Women who had had
      postpartum urinary retention did not have a higher prevalence of urinary stress
      incontinence.

PMID- 12237643
TI  - A prospective randomized safety trial of celecoxib for treatment of preterm
      labor.
AB  - OBJECTIVE: We compared the safety of celecoxib, a selective cyclo-oxygenase-2
      inhibitor, with the safety of the nonselective cyclo-oxygenase inhibitor
      indomethacin, when it was administered for treatment of preterm labor. STUDY
      DESIGN: In a randomized, double-blind, placebo-controlled trial, 24 pregnant
      women in preterm labor at 24 to 34 weeks of gestation received either
      indomethacin or celecoxib for 48 hours. Clinical assessment, fetal sonography,
      and Doppler blood flow studies of the fetal ductus arteriosus were performed
      daily. RESULTS: Mean maximum ductal flow velocity was significantly elevated over
      baseline (82.9 +/- 4.6 cm/s vs 111.14 +/- 14.3 cm/s; P =.02) after 24 hours of
      indomethacin, but not celecoxib. Both medications were associated with a
      transient decrease in amniotic fluid volume, with a greater effect by
      indomethacin. The medications were equally effective in the maintenance of
      tocolysis. There were no significant maternal or neonatal adverse events.
      CONCLUSION: In this initial evaluation, the safety of short-term celecoxib in
      women with preterm labor was superior to that of indomethacin.

PMID- 12237644
TI  - Exercise-related changes in umbilical and uterine artery waveforms as assessed by
      Doppler ultrasound scans.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of strenuous
      symptom-limited exercise on umbilical and uterine blood flow. STUDY DESIGN:
      Twenty-two primiparous women between 30 and 34 weeks of gestation were recruited.
      At rest, umbilical and uterine artery waveforms were assessed by measuring the
      pulsatility index. This was followed by a symptom-limited incremental exercise
      test. Fetal umbilical and maternal uterine artery circulations were assessed
      after exercise. RESULTS: Strenuous maternal exercise was demonstrated by the
      significant change in physiologic parameters, which was associated with an
      immediate increase in fetal heart rate, a significant increase in the right
      uterine artery pulsatility index, and a reduction in the umbilical artery
      pulsatility index. CONCLUSION: The modest change in the uterine artery
      pulsatility index without an adverse change in the umbilical artery pulsatility
      index indicates that a single bout of maximum symptom-limited exercise does not
      have immediate adverse fetal or maternal cardiovascular effects.

PMID- 12237645
TI  - The ninety-fifth percentile for growth discordance predicts complications of twin
      pregnancy.
AB  - OBJECTIVE: Our purpose was to define twin growth discordance on the basis of
      perinatal outcome. STUDY DESIGN: Twins delivered at >23 weeks' gestation between
      1995 and 2000 were identified by use of our computerized perinatal database.
      Birth weight (BW), chorionicity, and the following outcomes were recorded:
      cesarean delivery for nonreassuring fetal status (NRFS), umbilical artery (UA)
      pH, 5-minute Apgar score, neonatal intensive care unit (NICU) admission, and
      stillbirth. Discordance was calculated as 100 x(Larger BW - Smaller BW)/Larger
      BW. The distribution of discordance values for the study population was
      determined. Outcomes were compared for twins with and without discordance at
      thresholds defined by population percentile. RESULTS: The mean discordance for
      346 twins was 11.4% +/- 10.5%. The 75th percentile was 16% discordance, the 90th
      was 23%, and the 95th was 31%. Discordance was independently associated with
      outcomes. The 95th percentile was the threshold most predictive of cesarean
      section NRFS, UA pH <7.1, 5-minute Apgar score <7, and NICU admission.
      CONCLUSION: Defining pathologic discordance as the 95th percentile, or >30%
      difference, enhances its predictive value.

PMID- 12237646
TI  - Physical properties of the chorioamnion throughout gestation.
AB  - OBJECTIVE: Our purpose was to assess the tensile strength of the chorioamnion at
      various gestational ages. STUDY DESIGN: Segments of chorioamnion were obtained
      from 35 patients delivered at gestational ages ranging from 17 to 41 weeks.
      Clinical information including gestational age, chorioamnionitis, premature
      rupture of membranes, and onset of labor was recorded. Tensile strength (grams to
      burst and deflection at rupture) was measured on 2 to 16 specimens per patient.
      Tensile strength of several commercial products was used for comparison. RESULTS:
      Tensile strength increases up to 20 weeks of gestation and then plateaus until 39
      weeks of gestation, when it falls dramatically. Clinical chorioamnionitis alone
      did not affect tensile strength, but gross membrane inflammation resulted in
      reduced tensile strength. CONCLUSIONS: Tensile strength of the chorioamnion
      varies with gestational age. This baseline information will be useful in
      assessing the effects of various conditions and therapies on membrane strength
      and may provide insight into spontaneous rupture of membranes.

PMID- 12237647
TI  - Plasma nitric oxide levels and the expression of P-selectin on platelets in
      preeclampsia.
AB  - OBJECTIVE: The purpose of this study was to investigate the correlation of plasma
      nitric oxide levels with the expression of P-selectin on platelets in
      preeclampsia. STUDY DESIGN: Plasma levels of nitrite and nitrate (the stable
      nitric oxide metabolites) and the expression of P-selectin on platelets (a
      platelet activation marker) were measured in 25 normal pregnant women and 25
      women with preeclampsia. The effects of the inhibition of nitric oxide synthesis
      on the expression of P-selectin also was measured in vitro. RESULTS: Plasma
      nitrate levels and the expression of P-selectin averaged 30.5 +/- 2.2 micromol/L
      and 8.9% +/- 1.1% (SEM), respectively, in preeclampsia, which was significantly
      higher than in normal pregnancy (P <.05). Nitric oxide synthesis inhibition in
      vitro significantly increased the expression of P-selectin in normal pregnancy by
      284% (P <.05), which was significantly higher than in preeclampsia (156%, P
      <.05). CONCLUSION: The inhibitory effects of increased nitric oxide on the
      expression of P-selectin is attenuated in preeclampsia, which may contribute
      partly to the pathogenesis of preeclampsia.

PMID- 12237648
TI  - Length of hospital stay, obstetric conditions at childbirth, and maternal
      readmission: a population-based cohort study.
AB  - OBJECTIVE: We assessed the association between obstetric conditions, length of
      hospital stay for childbirth, and maternal readmission. STUDY DESIGN: A
      population-based cohort study was conducted on obstetric deliveries (N =
      2,652,726) in Canada from 1989 to 1999. Women who were readmitted to the hospital
      because of obstetric causes within 60 days of initial discharge were identified.
      RESULTS: Among the readmitted cases, women with cesarean deliveries were more
      likely to be readmitted to the hospital in the first week after discharge than
      women with vaginal deliveries (53% vs 41%). After an adjustment for maternal age
      by means of a Cox regression model, the risk of maternal readmission after
      cesarean delivery was significantly increased by 21%, 18%, and 10% for mothers
      with a length of hospital stay of <or=2, 3, and 4 days, respectively, compared
      with mothers with a length of hospital stay of 5 days. Postpartum hemorrhage,
      major puerperal infection, and some hypertensive disorders were associated with
      an elevated risk for maternal readmission and were also the major causes of
      readmission. CONCLUSION: Short length of hospital stay and several obstetric
      conditions appear to increase the risk of readmission in women with cesarean
      birth.

PMID- 12237649
TI  - Platelet activation in the hypertensive disorders of pregnancy.
AB  - OBJECTIVE: The purpose of this study was to determine whether platelet activation
      occurs only in preeclampsia or also in normal pregnancy. STUDY DESIGN: Thirty
      women with preeclampsia, 30 women with gestational hypertension, 20 women with
      essential hypertension, 30 pregnant women with normotension, and 30 nonpregnant
      women were recruited at St George Hospital, Sydney, Australia. Platelet
      activation was determined by flow cytometry on whole blood samples. RESULTS:
      Platelet activation was similar in all groups, except the group with
      preeclampsia. Compared with normal pregnant women, women with preeclampsia had
      significantly greater CD62 expression (1.35% vs 0.61%; P =.002), CD63 expression
      (1.73% vs 0.95%; P <.0001) and annexin V binding (1.03% vs 0.66%;P =.03) and
      significantly fewer circulating platelet microparticles (33 vs 49 x10(9)/L; P
      =.001). This was unrelated to other parameters that included platelet counts.
      Women with gestational hypertension in whom preeclampsia developed did not have
      enhanced platelet activation profiles. CONCLUSION: Platelet activation is
      increased in preeclampsia but not in other hypertensive disorders or in normal
      pregnancy. This may be part of the pathophysiologic factors of preeclampsia
      complications but is not predictable by the platelet count and is not apparent in
      all women with preeclampsia.

PMID- 12237650
TI  - Ethical challenges of decision making with pregnant patients who have
      schizophrenia.
AB  - OBJECTIVE: Because there is a dearth of literature, we developed an ethical
      framework to guide decision making about the management of pregnancy of patients
      with schizophrenia. STUDY DESIGN: We review pertinent literature on schizophrenia
      and pregnancy, including information on maternal and fetal risks and outcomes,
      and relate this information to ethical concepts. RESULTS: The ethical framework
      has five components: the concept of chronically and variably impaired autonomy,
      assisted decision making, surrogate decision making, strategies for dealing with
      the physician's feelings in response to these patients, and the concept of the
      fetus as a patient. We apply this ethical framework to clinical challenges of
      decision making during pregnancy with this patient population. CONCLUSIONS: The
      preventive ethics strategies of assisted and surrogate decision making can be
      used to prevent ethical conflicts in decision making about the management of
      pregnancy of patients with schizophrenia. These preventive ethics strategies
      should contribute significantly to reducing the vulnerability of these patients
      and therefore to enhancing their autonomy in the physician-patient relationship.

PMID- 12237651
TI  - Increased risk of preeclampsia among nulliparous pregnant women with idiopathic
      hematuria.
AB  - OBJECTIVE: Our purpose was to determine the risk of preeclampsia and gestational
      hypertension among nulliparous pregnant women with idiopathic hematuria. STUDY
      DESIGN: We conducted a prospective cohort study using data from the trial of
      Calcium for Preeclampsia Prevention (CPEP). Participants were followed up from
      screening and enrollment (gestational weeks 11-21) throughout pregnancy. Our
      analysis was limited to women who had been followed up to at least 20 weeks'
      gestation, had outcome information available, and were not suspected to have had
      urolithiasis. Surveillance for hematuria was conducted with dipsticks on clean
      catch urine specimens obtained at research clinic visits. Idiopathic hematuria
      was defined as hematuria identified at regularly scheduled clinic visits in the
      absence of urinary tract infection and before the onset of labor. Logistic
      regression was used to estimate the risk of preeclampsia among women with
      hematuria compared with women without hematuria. RESULTS: Among the 4307 women
      available for analysis, 132 (3%) had idiopathic hematuria during pregnancy.
      Idiopathic hematuria was associated with an almost 2-fold increased odds for
      development of preeclampsia (adjusted odds ratio [aOR] = 1.89, 95% CI 1.12- 3.18)
      but not with increased odds of gestational hypertension (aOR = 0.78, 95% CI 0.46
      1.32). CONCLUSIONS: Idiopathic hematuria identified during pregnancy is
      associated with greater risk of preeclampsia but not gestational hypertension.

PMID- 12237652
TI  - Obstetrician preferences for prenatal strategies to reduce early-onset group B
      streptococcal infection in neonates: a population-based survey.
AB  - OBJECTIVE: In light of a recent proposal to legislate group B streptococcal
      prevention strategies in New Jersey, this study examined obstetrician preferences
      and practices toward group B streptococcal prevention strategies in neonates.
      STUDY DESIGN: This was a mail survey of American College of Obstetricians and
      Gynecologists Fellows in New Jersey. Physician characteristics, existing
      guideline preferences, and reported actual group B streptococcal prevention
      practices were measured. RESULTS: Of the 695 potential respondents, 306 responses
      (44.7%) were received for analysis. Respondent stated preferences were for
      guidelines from the Centers for Disease and Prevention (74.5%), American College
      of Obstetricians and Gynecologists (12.7%), American Academy of Pediatrics
      (9.2%), and others (3.6%). The proportions of obstetricians who actually adhere
      to their stated preference were 57.5%, 64.1%, and 39.3% in Centers for Disease
      and Prevention, American College of Obstetricians and Gynecologists, and American
      Academy of Pediatrics group, respectively. Only 40.7% of the obstetricians
      cultured the anorectal/vaginal area for group B streptococcal carriers. An
      overwhelming 86.7% of obstetricians do not support legislation that regulates
      neonatal group B streptococcal preventing practices. CONCLUSIONS: Obstetrician
      preferences for use of existing group B streptococcal guidelines are often not
      reflected by their actual stated practices. However, obstetricians do not support
      legislative regulation of group B streptococcal prevention practices.

PMID- 12237653
TI  - Fetal genotypes and pregnancy outcomes in 35 families with mitochondrial
      trifunctional protein mutations.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of fetal
      genotype on maternal and fetal outcomes in families with mitochondrial
      trifunctional protein mutations in the United States. Trifunctional protein has 3
      enzymatic activities that include long-chain 3-hydroxyacyl-CoA dehydrogenase,
      which catalyzes long-chain fatty acid beta-oxidation. STUDY DESIGN: We analyzed
      pregnancy history and offspring genotypes in 35 families with heterogeneous
      mutations. The fetal genotype was determined in utero in 11 pregnancies and after
      birth in 50 pregnancies. RESULTS: Forty-nine percent of the women who carried
      affected fetuses had acute fatty liver of pregnancy. Another 11% of the women had
      the syndrome of hemolysis, elevated liver enzymes, and low platelets, or
      preeclampsia. All women who had the maternal illness carried fetuses with
      isolated long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Sixty-eight
      percent and 43% of the affected pregnancies also were associated with premature
      delivery and intrauterine growth retardation, respectively. No maternal or fetal
      complications were associated with heterozygous or wild-type fetal genotypes.
      CONCLUSION: Fetal mitochondrial trifunctional protein defects should be
      considered a cause for maternal liver disease, preterm labor, and intrauterine
      growth retardation.

PMID- 12237654
TI  - Hospital primary cesarean delivery rates and the risk of poor neonatal outcomes.
AB  - OBJECTIVE: The purpose of this study was to determine whether risk-adjusted
      hospital primary cesarean delivery rates are associated with poor neonatal
      outcomes. STUDY DESIGN: The Washington State Birth Events Records for 1995 and
      1996 were used. Predicted primary cesarean delivery rates were calculated for
      each hospital. Women were divided by whether the hospital had an actual primary
      cesarean delivery rate below, within, or greater than the predicted CI. Asphyxia
      (a lack of oxygen that leads to organ damage) was used as a marker of poor
      neonatal outcome. Risk of neonatal asphyxia was compared for each of the 3
      cesarean rating groups. RESULTS: The risk for asphyxia among infants who were
      born to women who delivered at hospitals that had more, within, or fewer cesarean
      deliveries than predicted were 0.58%, 0.17%, and 0.33%, respectively (P <.0001).
      CONCLUSION: Infants born to women who delivered at hospitals that had more than
      or fewer than the predicted number of primary cesarean deliveries experienced a
      greater risk of neonatal asphyxia.

PMID- 12237655
TI  - Expression of angiogenic and neurotrophic factors in the human amnion and
      choriodecidua.
AB  - OBJECTIVE: Our objective was to identify the novel or differential expression of
      growth or development associated genes in the human gestational membranes that
      might play roles in pregnancy or in term or preterm parturition. STUDY DESIGN:
      Complementary DNA arrays were probed with [alpha(33)P]dCTP-labeled-complementary
      DNA that was prepared from the RNA of reflected amnion and choriodecidua that
      represent term not-in-labor, term spontaneous labor, and preterm labor with and
      without chorioamnionitis (n = 4 per group). Differential expression (term not-in
      labor vs term spontaneous labor or preterm labor with chorioamnionitis vs preterm
      labor without chorioamnionitis) was evaluated by Wilcoxon tests. RESULTS: All 16
      amnion samples expressed angiogenic factors (endothelin-2 and -3, vascular
      endothelial growth factor, and vascular endothelial growth factor-B) and
      neurotrophic factors (ephrin-A2, ephrin receptors-A2, -B1, -B3, -B4, and -B5,
      neuropilin-2, p75/nerve growth factor receptor and semaphorin-F). In both amnion
      and choriodecidua, the expression of vascular endothelial growth factor and the
      angiopoietin receptor, Tie-2, were greater with term spontaneous labor than with
      term not-in-labor (P <.05); increased VEGF receptor-2 (flk-1) expression was
      observed in term spontaneous labor choriodecidua (P <.05) but not amnion. Ephrin
      A1 expression increased with term spontaneous labor in both tissues (P <.05).
      Semaphorin-F expression decreased with preterm labor with chorioamnionitis in
      choriodecidua (P <.05), although the trend was not significant in amnion (P =.1).
      CONCLUSION: Neurotrophic and angiogenic factor genes are expressed in amnion and
      choriodecidual membranes. Several of the genes exhibit differential expression
      with labor at term or in association with infection preterm, which suggests roles
      in or associated with these processes.

PMID- 12237656
TI  - Insulin, insulin-like growth factor-1, and insulin resistance in women with
      pregnancy-induced hypertension.
AB  - OBJECTIVE: The purpose of this study was to assess insulin, insulin sensitivity,
      and insulin-like growth factor-I in women with preeclampsia and gestational
      hypertension. STUDY DESIGN: Insulin resistance was measured with the short
      insulin-tolerance test in 20 women with preeclampsia, in 18 women with
      gestational hypertension, and in 20 normotensive control subjects. Sex hormone
      binding globulin, insulin-like growth factor-I, glucose, fructosamine,
      glycosylated hemoglobin, insulin, C-peptide, and lipids were measured in the
      fasting state. RESULTS: Women with gestational hypertension had a significant
      lower insulin sensitivity index (0.13 +/- 0.1) and a higher level of insulin-like
      growth factor-I (333.71 +/- 107.6 ng/mL) than women in the control group (0.21 +/
      0.1 [P <.05]; 218.11 +/- 82.3 ng/mL [P <.01]) and women with preeclampsia (0.21
      +/- 0.12 [P <.05]; 234.78 +/- 92.76 ng/mL [P <.01]). There were no significant
      correlations between insulin sensitivity index and insulin-like growth factor-I.
      CONCLUSION: Insulin resistance is present in women with gestational hypertension
      but not in women with preeclampsia and did not correlate with insulin-like growth
      factor-I.

PMID- 12237657
TI  - The effect of a maternal infusion of amino acids on umbilical uptake in
      pregnancies complicated by intrauterine growth restriction.
AB  - OBJECTIVE: To establish whether, in human pregnancies complicated by intrauterine
      growth restriction (IUGR), the maternal intravenous infusion of amino acids can
      increase fetal amino acid concentrations and umbilical uptake. STUDY DESIGN:
      Before elective cesarean delivery, a solution of amino acids was infused into a
      maternal vein in 8 patients with pregnancies complicated by IUGR (experimental
      group). At cesarean delivery, maternal, umbilical venous, and arterial blood
      samples were obtained. Ten comparable IUGR pregnancies were compared with those
      in the experimental group. RESULTS: In the experimental group, all maternal amino
      acid concentrations were increased significantly. In the umbilical vein, valine,
      methionine, isoleucine, leucine, phenylalanine, arginine, serine, glycine, and
      proline concentrations were elevated. Umbilical venoarterial differences of amino
      acid per mole of oxygen for leucine, isoleucine, methionine, arginine, glycine,
      serine, and proline were elevated but not for lysine, histidine, threonine,
      valine, and phenylalanine. CONCLUSION: In pregnancies complicated by IUGR,
      increasing the maternal concentration of amino acids leads to an increased
      umbilical uptake of some of the amino acids to the fetus. There was no evidence
      of a change in the uptake of 3 essential amino acids: lysine, histidine, and
      threonine.

PMID- 12237658
TI  - Patients with prior second-trimester loss: prophylactic cerclage or serial
      transvaginal sonograms?
AB  - OBJECTIVE: To compare management with prophylactic cerclage versus serial
      transvaginal sonograms of the cervix in patients with prior second-trimester
      loss. STUDY DESIGN: Singleton pregnancies with prior second-trimester spontaneous
      loss between 14 and 24 weeks' gestation were retrospectively reviewed. At the
      obstetricians' discretion, some were managed with prophylactic cerclage and some
      with serial transvaginal sonograms of the cervix, starting at 14 weeks, and
      cerclage only if cervical length was <25 mm or funneling was >25% before 24
      weeks. All cerclages were McDonald. Primary outcome was preterm delivery at <35
      weeks. RESULTS: Of 177 patients with singleton pregnancies who had prior second
      trimester loss identified, 66 received prophylactic cerclage and 111 were
      followed up with transvaginal sonography, of which 36% (40/111) had therapeutic
      cerclage because of cervical changes. The two management groups of prophylactic
      cerclage versus transvaginal sonography of the cervix did not differ in any
      measure of obstetric outcome, including preterm delivery at <35 weeks (23% vs
      30%; P =.3), preterm delivery at <33 weeks (21% vs 26%; P =.5), or gestational
      age at delivery (34.6 +/- 6.8 weeks vs 34.4 +/- 6.8 weeks; P =.8). CONCLUSION: In
      patients with prior second-trimester loss, serial transvaginal sonography of the
      cervix, with cerclage only if indicated by cervical changes, is a valuable
      alternative to a policy of uniform prophylactic cerclage.

PMID- 12237659
TI  - The association between maternal factors and perinatal outcomes in triplet
      pregnancies.
AB  - OBJECTIVE: The purpose of this study was to evaluate the associations between
      maternal factors and outcomes in triplet pregnancies. STUDY DESIGN: This was a
      historic cohort study of 194 triplet pregnancies of >or=24 weeks of gestation
      that were delivered from 1983 through 2001 from five medical centers. RESULTS: In
      analyses that were limited to pregnancies with all live-born triplets (178
      pregnancies), women with a previous good outcome (>2500 g + >37 weeks of
      gestation) had longer gestations (+7.9 days, P =.03), better rates of fetal
      growth (+4.9 g/wk, P <.0001), and higher birth weights (+153 g, P <.0001).
      Maternal weight gains of <36 pounds by 24 weeks of gestation were associated with
      lower birth weights (-197 g, P <.0001), and fetal growth rates at <or=25th
      percentile were associated with a shorter length of gestation (-36.7 days, P
      <.0001). CONCLUSION: Previous obstetric outcome and weight gain by 24 weeks of
      gestation were associated significantly with fetal growth rate and birth weight;
      fetal growth rate, in turn, was associated significantly with length of
      gestation.

PMID- 12237660
TI  - Double-positive maternal serum screening results for down syndrome and open
      neural tube defects: An indicator for fetal structural or chromosomal
      abnormalities and adverse obstetric outcomes.
AB  - OBJECTIVE: The study was designed to evaluate whether double positive maternal
      serum screening results for Down syndrome and open neural tube defects indicate
      an increased risk of adverse perinatal outcome. STUDY DESIGN: A retrospective
      case-control study was conducted. In a cohort of 170,394 women who underwent
      maternal serum triple screening in Ontario, Canada, between October 1995 and
      September 1998, 189 women received positive screening results for both Down
      syndrome and neural tube defects. Each case was matched to 5 control subjects who
      had negative screening results for test center, maternal age, and specimen date.
      The risks for adverse perinatal outcomes were compared. RESULTS: Women with
      double-positive screening results had significantly higher risks of having
      fetuses with structural abnormalities (odds ratio, 14.5) and chromosomal
      anomalies (odds ratio, 36.3). They also had higher risks of having preeclampsia
      (odds ratio, 6.7), small-for-gestational age (odds ratio, 9.7), preterm delivery
      (odds ratio, 5.9), miscarriage, and intrauterine fetal death (odds ratio, 11.8).
      CONCLUSION: Double-positive maternal serum screening results are associated with
      fetal structural and chromosomal abnormalities and/or adverse pregnancy outcomes.
      Close fetal and maternal surveillance are indicated when such pregnancies are
      identified.

PMID- 12237661
TI  - Decreased vascularization and cell proliferation in placentas of intrauterine
      growth-restricted fetuses with abnormal umbilical artery flow velocity waveforms.
AB  - OBJECTIVE: The purpose of this study was to compare the morphologic features of
      placentas in severe intrauterine fetal growth restriction with abnormal umbilical
      artery blood flow velocity waveforms and normal gestation. STUDY DESIGN:
      Immunohistochemical methods were used to evaluate cell proliferation, vascular
      density, and alpha-smooth muscle actin expression by stromal cells in a group of
      9 age-matched intrauterine growth-restricted and control placentas at 25 to 41
      weeks of gestation. RESULTS: Fewer MIB1-positive nuclei were observed in both
      trophoblast and stromal cell populations in intrauterine growth restriction,
      which indicates fewer cells in cycle. Furthermore, a greatly reduced vascular
      density was observed, along with higher levels of alpha-smooth muscle actin
      expression in stromal cells. CONCLUSION: Intrauterine growth-restricted placentas
      show reduced cell proliferation in both trophoblast and stromal cell
      compartments. Peripheral villous vascularization is highly reduced.

PMID- 12237662
TI  - Lead in breast milk and maternal bone turnover.
AB  - OBJECTIVE: Our purpose was to determine whether breast milk lead (Pb) levels are
      correlated with maternal blood Pb levels, bone loss, or bone turnover during
      reproduction. STUDY DESIGN: Data were collected prospectively at 0, 1.5, 3, 6,
      and 12 months after delivery in 15 lactating and 30 bottle-feeding women.
      Variables included breast milk Pb (inductively coupled mass spectrometry),
      maternal blood Pb (atomic absorption spectrophotometry), osteocalcin
      (radioimmunoassay), and bone mineral density change (dual-energy x-ray
      absorptiometry). RESULTS: Mean Pb breast milk concentrations were 6.1, 5.6, 5.9,
      and 4.3 ng/mL at the 1.5, 3, 6, and 12 months post partum, whereas mean maternal
      blood Pb concentrations were 1.4, 1.6, 1.7, and 1.4 microg/dL at 0, 3, 6, and 12
      months post partum. The 5.6% bone loss and significant bone turnover were related
      to breast milk Pb levels but not to postpartum maternal blood Pb levels. Maternal
      and breast milk Pb values were modestly correlated at 1 to 2 months. CONCLUSIONS:
      Bone loss and bone turnover were related to breast milk Pb levels. In these
      women, there was no evidence that either high maternal blood or breast milk Pb
      concentrations are a major public health concern.

PMID- 12237663
TI  - Vitamin C and E supplementation in women at risk of preeclampsia is associated
      with changes in indices of oxidative stress and placental function.
AB  - OBJECTIVE: We have previously reported a reduced incidence of preeclampsia in
      women who were at risk and were taking vitamin C (1000 mg/d) and vitamin E (400
      IU/d) supplements. In this study, we determined whether supplementation in the
      same cohort was associated with an improvement in indices of placental
      dysfunction and oxidative stress toward values determined in women who were at
      low risk of preeclampsia. STUDY DESIGN: Seventy-nine women who were at high risk
      and who were taking vitamin supplements and 81 who were taking placebos were
      compared with 32 women who were at low risk and who were not taking supplements
      who were studied simultaneously. RESULTS: Indices of oxidative stress and
      placental function were abnormal in the placebo group. When the placebo group was
      compared with the women who were at low risk, ascorbic acid, plasminogen
      activator inhibitor-2, and placenta growth factor concentrations were decreased;
      and 8-epi-prostaglandin F(2alpha),leptin, and the plasminogen activator inhibitor
      1/-2 ratio were increased. In the group that received vitamin supplements,
      ascorbic acid, 8-epi-prostaglandin F(2alpha), leptin, and plasminogen activator
      inhibitor-1/-2 values were similar to women who were at low risk. CONCLUSION:
      Antioxidant supplementation in women who were at risk of preeclampsia was
      associated with improvement in biochemical indices of the disease.

PMID- 12237664
TI  - Decidual relaxins: gene and protein up-regulation in preterm premature rupture of
      the membranes by complementary DNA arrays and quantitative immunocytochemistry.
AB  - OBJECTIVE: This study was undertaken to show both decidual relaxin gene and
      protein up-regulation in preterm premature rupture of the fetal membranes. STUDY
      DESIGN: Membranes after preterm premature rupture (n = 4) have been matched in
      pairs with preterm intact membranes (n = 4). These tissues were from patients
      without infection, labor, preeclampsia or intrauterine growth restriction, and
      none of the patients had a latency period of more than 8 hours. The messenger
      RNAs from these tissues were used on complementary DNA expression arrays; 488
      genes were analyzed. Relaxin gene expression was quantitated from the arrays and
      in additional tissues by Northern analysis. The two relaxin proteins, H1 and H2,
      in the decidual cells were immunolocalized and quantitated by microdensitometry
      with the use of specific antisera that were raised to decapeptides over the
      region of least homologic features. The expression of five other genes that were
      selected from the arrays were quantitated by Northern analysis. RESULTS: Relaxin
      gene expression was up-regulated 3.4-fold on the complementary DNA arrays but was
      not confirmed on Northern analysis. On the other hand, protein analysis for
      relaxin H1 and H2 in the decidual cells showed them to be significantly up
      regulated (P <.0001, for both proteins) in patients with preterm premature
      rupture of the membranes compared with control subjects. The 20 most highly
      expressed genes at preterm in tissues without rupture were determined. In
      addition, analysis of the genes that were up-regulated with preterm rupture of
      the membranes showed 30 differentially expressed genes. CONCLUSION: Relaxin gene
      expression in the decidua is up-regulated, and its protein expression is
      significantly increased with preterm rupture of the fetal membranes.

PMID- 12237665
TI  - The effect of gender and gestational diabetes mellitus on cord leptin
      concentration.
AB  - OBJECTIVE: The purpose of this study was to determine the relationship of
      neonatal sex and gestational diabetes mellitus on cord leptin concentration and
      to determine whether cord leptin has a stronger correlation with fat mass
      compared with birth weight or lean body mass. We hypothesized that there are no
      significant differences in fetal leptin concentration between male and female or
      between neonates of mothers with gestational diabetes mellitus and control
      neonates, when adjusted for body composition. STUDY DESIGN: Cord blood leptin
      concentrations were measured in newborn infants of 78 women (44 control neonates
      and 34 gestational diabetes mellitus). Of the 78 neonates, 32 babies were female,
      and 46 babies were male. Birth weights were measured with a calibrated scale, and
      body compositions were measured by total body electrical conductivity. RESULTS:
      Estimated mean gestational age at delivery was 39.1 +/- 1.1 weeks for control
      neonates versus 38.6 +/- 1.3 weeks for neonates of mothers with gestational
      diabetes mellitus (P =.01). The fat mass for the control neonates and neonates of
      mothers with gestational diabetes mellitus was 0.36 +/- 0.15 kg versus 0.48 +/-
      0.21 kg (P =.01); the percent body fat for the control neonates and neonates of
      mothers with gestational diabetes mellitus was 10.5% +/- 3.8% versus 13.2% +/-
      4.3% (P =.006), respectively. There was no significant difference in cord leptin
      concentration between male and female neonates (16.0 +/- 13.8 ng/dL vs 12.7 +/-
      12.8 ng/dL, P =.24). Cord leptin concentrations (18.1 +/- 16.2 ng/dL vs 10.9 +/-
      9.5 ng/dL, P =.02) were significantly greater in neonates of mothers with
      gestational diabetes mellitus than in control neonates. In all subjects, cord
      leptin was significantly correlated with percent body fat (r = 0.51, P <.0001),
      fat mass (r = 0.49,P <.0001), and birth weight (r = 0.25, P =.03). After the
      adjustment for fat mass, there was no significant difference in cord leptin
      concentration between control neonates and neonates of mothers with gestational
      diabetes mellitus (P =.20), but there was a significant difference between male
      and female neonates (P =.04). However, when an adjustment was made for both fat
      mass and lean body mass, there was no longer a significant difference between
      male and female neonates (P =.12) CONCLUSION: The differences in cord leptin
      concentration between male and female neonates and between infants of women with
      gestational diabetes mellitus and control neonates are related to differences in
      body composition.

PMID- 12237666
TI  - Effects of antenatal glucocorticoids on outcomes of very low birth weight
      multifetal gestations.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that benefits of
      antenatal glucocorticoids to reduce death or major morbidities are similar in
      very low birth weight multiple and singleton infants. STUDY DESIGN: Infants with
      birth weight of 401 to 1500 g who were born from May 1991 through December 1999
      were evaluated with the use of the National Institute for Child Health and Human
      Development Neonatal Research Network registry data. The generalized estimating
      equations approach to multivariable logistic regression was used, with
      interaction between multifetal gestation and antenatal glucocorticoids as the
      primary independent variable. RESULTS: Mothers of multiple infants were more
      likely to receive antenatal glucocorticoids than mothers of singleton infants
      (66% vs 56%; P <.01). No interaction between multifetal gestation and antenatal
      glucocorticoids was noted for any study outcomes. The odds of death or major
      morbidity was decreased by antenatal glucocorticoids, advancing gestational age,
      increasing birth weight, female gender, and nonwhite race. CONCLUSION: If exposed
      to antenatal glucocorticoids, very low birth weight infants of multifetal
      gestations and very low birth weight singleton infants have similar risks of
      death or major morbidity.

PMID- 12237667
TI  - Fetal heart rate response to strenuous maternal exercise: not a predictor of
      fetal distress.
AB  - OBJECTIVE: The purpose of this study was to analyze the effects of maternal
      exercise on fetal heart rate changes to determine prognostic factors for an
      abnormal trace in labor. STUDY DESIGN: Two hundred fifty-eight primiparous women
      who were 33 to 38 weeks of gestation with varying levels of activity were
      recruited. A symptom-limited incremental exercise test was preformed.
      Cardiotocography was carried out before and after exercise. Data were analyzed
      with specialized computer software. RESULTS: A strenuous level of exercise was
      achieved. The most common fetal heart rate response seen was tachycardia. The
      incidence did not vary with the level of fitness, maternal body mass index, or
      fetal weight. Male fetuses were more prone to fetal distress. A significantly
      higher proportion of distressed babies were born to older women (P <.0001). The
      percentage of abnormal traces was equal in the vaginal and caesarean delivery
      groups. CONCLUSION: The results showed no correlation among the incidence of
      fetal distress, the mode of delivery, and the fetal heart rate changes after
      exercise.

PMID- 12237668
TI  - Use of cephalosporins during pregnancy and in the presence of congenital
      abnormalities.

PMID- 12237669
TI  - Clinical outcomes related to either the 1- or 2-hour postprandial glucose level
      in women with gestational diabetes.

PMID- 12237670
TI  - Treatment of early preterm spontaneous rupture of membranes.

PMID- 12237671
TI  - Pelvic embolization for treatment of hemorrhage related to spontaneous and
      induced abortion.

PMID- 12237672
TI  - Recalculation of gestational sac losses in multifetal pregnancy.

PMID- 12237673
TI  - Value of bilateral hypogastric artery occlusion for severe obstetric hemorrhage.

PMID- 12237674
TI  - Erythromycin use during pregnancy in relation to pyloric stenosis.

PMID- 12237675
TI  - On the Molecular Mechanism of the Tumor Suppressor Function of cDNA Clone p14-6.
AB  - Interactions between the RNA transcript of the tumor suppressor cDNA clone, p14-6
      (the 3'untranslated region of the nuclear factor for human interleukin-6; NF-IL6
      3'UTR), and the reversion-related proteins BNF, were investigated. It was found
      that: (1) the recognition site of the RNA for BNFs was a 24-nucleotide segment
      located within the 3'-proximal U-rich sequence; (2) the BNFs were a group of
      proteins which may interact with each other before interacting with a site on the
      RNA as a protein complex; (3) possibly only one protein in the complex,
      namelyR62, directly bound to the RNA site.

PMID- 12237676
TI  - Cloning and Sequence Analyzing the Gene of Trichosanthes Trypsin Inhibitor.
AB  - A DNA probe for Trichosanthes trypsin inhibitor was amplified from the cDNA
      library of Trichosanthes kirilowii by polymerase chain reaction. Using this probe
      to screen the cDNA library, a full-length cDNA sequence of the inhibitor was
      obtained. The open reading frame encodes a Pre-Pro-inhibitor with Pre-, Pro, and
      mature peptides of 24, 14, and 27 residues, respectively. The deduced amino acid
      sequence of the mature peptide is consistent with that determined by the primary
      structure analysis of the protein.

PMID- 12237677
TI  - The Protection of Choline Dehydrogenase by Its Substrate.
AB  - Choline dehydrogenase, an enzyme bound to the mitochondrial inner membrane, plays
      an important role in the mitochondrial respiratory chain. The purified enzyme is
      different from the membrane bound enzyme in some properties. The inactivation
      effects of temperature and SDS on choline dehydrogenase were studied. It was
      found that the substrate choline had significant protective effect. It was
      suggested that its substrate could induce the conformational changes of choline
      dehydrogenase.

PMID- 12237678
TI  - Protein Engineering of Insulin: [B9 Glutamic Acid] Human Insulin.
AB  - B9Ser of insulin B chain was substituted by Glu using site-directed mutagenesis
      to obtain a fast-acting insulin-[B9Glu] human insulin. The receptor binding
      capacity and in vivo biological activity of [B9Glu] human insulin are 21% and 40%
      as those of porcine insulin respectively.

PMID- 12237679
TI  - The Receptor Binding and Biological Activity of [B1-Ala, B2-Ala]-insulin.
AB  - The receptor binding properties with human placental membrane (HPM) and the in
      vitro biological activity of an insulin analogue, [B1-Ala, B2-Ala]-insulin were
      investigated in detail and compared with those of insulin. It was found that the
      binding of (125)I-[B1-Ala, B2-Ala]-insulin and (125)I-insulin to HPM was time
      dependent reaching equilibrium after 6min at 37 degrees in the presence of
      bacitracin with an equilibrium maximum binding of 6.44 fmol/mg protein for [B1
      Ala, B2-Ala]-insulin and 3.47 fmol/mg protein for insulin The half time (T1/2) to
      reach equilibrium was 19 seconds for [B1-Ala, B2-Ala]-insulin and 25 seconds for
      insulin. [B1-Ala, B2-Ala]-insulin and insulin competed with specific (125)I-[B1
      Ala, B2-Ala]-insulin in a dose-dependent manner. From IC(50), the receptor
      binding activity of [B1-Ala, B2-Ala]-insulin was 139.6% compared with that of
      insulin. Scatchard analysis revealed that the receptor association constants of
      [B1-Ala, B2-Ala]-insulin in HPM at 4 degrees were 5.88x10(8)L/mol and
      7.63x10(5)L/mol respectively, while those of insulin were 4.83x10(8)L/mol and
      3.39x10(5)L/mol respectively. The in vitro activity of [B1-Ala, B2-Ala]-insulin
      was 130% of that of insulin in terms of lipogenesis in rat adipocytes.

PMID- 12237680
TI  - The Cloning and Construction of a Murine-human Chimeric Antibody with Specificity
      for HBsAg and the Expression of the Chimeric Heavy Chain in E. coli.
AB  - The genes encoding the heavy and light chain variable regions (V(H) and V(K)) of
      the murine monoclonal antibody with the specificity for hepatitis B virus surface
      antigen (HBsAg) have been clone by using RT-PCR. They were combined to the Human
      C(gamma)(3) and C(K) genes respectively to construct the murine human chimeric
      antibody genes The chimeric heavy chain was expressed in E. coli, and
      characterized by SDS-PAGE, Western-blot, indirect ELISA Assay to demonstrate the
      expression product has the HBsAg-binding ability.

PMID- 12237681
TI  - Cloning of Human Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) cDNA
      and Its Expression in E. coli.
AB  - Human GM-CSF cDNA fragment encoding the mature GM-CSF was obtained by using RT
      PCR method with total RNA extracted from induced human fetal lung cells HFL. The
      sequence of the h GM-CSF cDNA thus obtained was the same as those reported. In
      order to get expression of a high level in, the 5' terminal nucleotide sequence
      of hGM-CSF cDNA was modified by using PCR. The modified h GM-CSF cDNA was
      inserted into plasmid pET-11d containing T7 promoter, with the resulted
      expression of plasmid pETC-5. E. coli BL21(DE3) was transformed with pETC-5 and
      an expressed strain BLEC4 was selected. SDS-PAGE analysis revealed the rhGM-CSF
      was produced and accumulated up to 16% of the total cellular protein in the form
      of inclusion body in BLEC$ cells after induced by 0.5 mM IPTG for 2 h. ELISA and
      TF-1 cell culture assay showed that the biological activity of the partially
      purified and renatured rhGM-CSF was similar to that of the natural human GM-CSF.

PMID- 12237682
TI  - Effects of Site-specific Mutagenesis of K253 and N184V on the Thermostability of
      D-Glucose Isomerase.
AB  - In order to enhance the thermostability of D-Glucose isomerase (GI), its mutants,
      GIK253R and GIN184V, were obtained with the double primer method of site-directed
      mutagenesis. Then their biochemical properties were assayed and compared with
      wild-type GI. The results showed that: (1) The mutant K253R was less stable than
      the wild-type GI at 70 degrees and 80 degrees. But in 1 M L-Rhaminose at 70
      degrees, they had similar rate of heat inactivation. Furthermore, the mutant
      K253R has higher specific activity than the wild-type GI. (2) The mutant N184V
      had much less thermostability and specific activity as compared with the wild
      type GI. These results were explained by their kinetic parameters and crystal
      structure model.

PMID- 12237683
TI  - Computer Analysis of the Cleavage Reaction of Hammerhead Ribozyme.
AB  - We have analyzed various in vitro cleavage reactions of hammerhead ribozyme by a
      computer program. Three energy changes: deltaE(s'), deltaE(r'), and deltaE, were
      calculated. deltaE(s') was the hypothetical energy requirement for the substrate
      to be activated from the most stable state to the relaxed state. deltaE(r') was
      the same energy requirement for the ribozyme. deltaE was the calculated free
      energy decrease by the formation of Rz-S complex from the relaxed ribozyme and
      the substrate. We found that high deltaE(s') or deltaE(r') reduced the cleavage
      efficiency of the reaction, and that the deltaE was related to both cleavage
      efficiency and the optimal temperature of the reaction. deltaE(s'), deltaE(r')
      can be calculated in advance according to the sequences of the ribozyme and the
      substrate. Our model, therefore, can be use in the designing of ribozymes.

PMID- 12237684
TI  - The regulation of N-Acetylglucosaminyl Transferase III by Protein Kinase C.
AB  - The activity of N-acetylglucosaminyl transferase III (GnT III) in 7721 human
      heptocarcinoma cell was inhibited by two non-specific Ser/Thr protein kinase
      inhibitors, quercetin and trifluoperazine, and two PKC specific inhibitors, D
      sphingosine and staurosporine. The change of GnT III activity paralleled that of
      membranous PKC (m-PKC) when the cells were treated with PMA, but not with that of
      cytosolic PKC (c-PKC). Quercetin, D-sphingosine and staurosporine also blocked
      the PMA activation of GnT-III. The inhibitory effects on m-PKC and GnT III were
      generally proportional to the concentration of quercetin and staurosporine. When
      crude GnT preparations of human and rat kidney were treated with ALP to remove
      the phosphate groups, the GnT III activities were significantly decreased. These
      results suggest that GnT III may be regulated by m-PKC directly or indirectly via
      the phosphorylation/dephosphorylation of the Ser/Thr residue.

PMID- 12237685
TI  - The Rapid Identification of Protein Through Its Amino Acid Composition.
AB  - This paper described a method for the identification of protein through its
      composition. The basic idea is as follows: A database for lengths, compositions
      and molecular weights of all known proteins is easily derived from a protein
      sequence database and by comparing the composition, length and molecular weight
      of the protein in question with each array of data in the composition database,
      proteins with similar length, composition and molecular weight may be found; as
      such a tentative identification for the said protein may be made. In some cases,
      it can be perfectly accurate to predict the right protein(s) from the composition
      database. A computer program applying this method was developed and used to
      search for the compositions of human insulin precursor and other proteins. The
      results are good, which proves that it is a fast and economic way to identify a
      protein based on its amino acid composition.

PMID- 12237686
TI  - Studies on the Conformation of Apocytochrome c in Different Folding States
      Inserted into the Membranes.
AB  - Correlation between the folding states of the chicken heart apocytochrome c and
      its membrane insertion ability was studied by the monolayer experiment. The
      penetration ability of apocytochrome c decreased with its folding. Intrinsic
      fluorescence emissions of apocytochrome c interacted with soybean phospholipids
      liposomes suggested that the conformations of apocytochrome c with different
      folding states in aqueous solution were also different in the membranes. The
      conformational differences were further characterized by CD spectra of
      apocytochrome c interacted with DMPC and DMPG liposomes. The results showed that
      apocytochrome c, which were randomly coiled in aqueous solution, adopted alpha
      helical conformations after interaction with DMPG liposome. The apocytochrome c
      with a folded state in aqueous solution also adopted alpha-helical conformations,
      but the alpha-helical contents were less than the former. When DMPC liposomes
      were used, no distinct conformational change was observed.

PMID- 12237687
TI  - The Self-association of Melittin at Low Concentration in Aqueous Solution.
AB  - The intrinsic fluorescence emission, polarization and Trp-19 quenching of
      melittin in the aqueous solution showed that even with concentration as low as 2
      &mgr;M, the self-association of melittin still occurred. The transition preferred
      to occur under acidic condition and the stability of the associated melittin was
      dependent on the pH value of the solution.

PMID- 12237688
TI  - Studies on the PEGylation of Protein at a Specific Site: Sulfhydryl-PEGylation of
      97Cys-IFN-gamma.
AB  - Human recombinant interferon-gamma(IFN-gamma) is not glycosylated at site 25 Asn
      or 97 Asn, but its bioactivity is the same as the native one. So we suppose that
      mutants 25/97Cys-IFN-gamma and PEG-25/97-Cys-IFN-gamma have the same bioactivity
      as native. By site-directed mutagenesis, the 97Cys-IFN-gamma was obtained and
      modified with a new PEGylation reagent which was prepared by us with a very
      simple method. The results were coincident with our previous supposition that
      mutagenesis at glycosylation site 97 from Asn to Cys and PEGylation at 97 Cys
      have no effect on the activity of IFN-gamma, which were about 7x10(6) IU/mg. If
      the work was of universal significance, it will be important both in theory and
      application. Therefore, further study will be done in the future.

PMID- 12237689
TI  - Interaction of the Yeast PH02 Protein or Its Mutants with the PHO5 UAS in vitro.
AB  - The GST gene fusion system was used to express PHO2 gene and its mutants in E.
      coli Gel retardation assays showed that PHO2 fusion protein can bind to the
      upstream activation sequence (UAS) of the acid phosphatase gene PHO5. The
      homeodomain of PHO2 protein has such structure as alpha-helix 2-beta-turn-alpha
      helix 3, which acts as the DNA binding domain of the transcriptional factor. The
      Mutation of lle 123 to Pro in helix 3 or the insertion of 4 amino acids (PDPD)
      between 112 and 113 in alpha-helix 2 led to the complete loss of DNA-binding
      activity of PHO2, while the mutation of Pro 117 to Ala in beta-turn did not
      affect the binding activity significantly. Deletions of the PHO80 homologous
      region, acidic region or C-terminal 132 residues had no great effect on the DNA
      binding activity, although these mutants had lost the ability to activate PHO5
      expression in vivo.

PMID- 12237690
TI  - The Effect of Buckyball C(60) Irradiation on the Fluidity of Erythrocyte
      Membranes.
AB  - The erythrocyte membranes were prepared from fresh human blood and 1,6-dipheny1
      1,3,5-hexatriene (DPH) was used as a probe to detect their change of fluidity. It
      was found that after brief irradiation, C(60) remarkably increased the degree of
      fluorescence polarization of the DPH-labeled erythrocyte membrane, suggesting
      that C(60) irradiation could greatly reduce the fluidity of erythrocyte membrane.
      It was also found that the reduction of membrane fluidity was mainly due to the
      oxidation of sulfhydry groups in the membrane protein and the peroxidation of
      membrane unsaturated fatty acids.

PMID- 12237691
TI  - Cloning and Expression of the Yeast Saccharomyces cerevisiae MyristoyL-CoA:
      Protein N-Myristoyltransferase Gene.
AB  - The gene encoding the myristoyl-CoA: protein N-myristoyltransferase from yeast S.
      cerevisiae (YSCNMT) has been amplified with the synthetic oligonucleotides by
      PCR, cloned into the pBluescript KS+ vector and analyzed by DNA sequencing. Then,
      an expression plasmid (pMFT7-5-NMT) containing the cloned YSCNMT gene controlled
      by T7 promoter has been constructed and transformed into E. coli BL21(DE3).
      Analyzed by SDS-PAGE, an IPTG-induced product with the same molecular size (53
      kD) as that deduced from the known YSCNMT amino acid sequence was observed. It
      accounted for about 39% of the total cellular proteins, the soluble form of which
      accounted for about 34% of the total soluble cellular proteins and was purified
      to homogeneity in a single step using P11 phosphocellulose chromatography. The N
      terminal amino acid sequencing revealed that the expressed protein began with the
      sequence encoded by the cloned YSCNMT gene and did not contain the N-terminal
      methionine. It was also observed that the expressed product had apparent YSCNMT
      activity in the in vitro assay.

PMID- 12237692
TI  - Sugar Binding Activity of Lectin Fragments.
AB  - Some sugar binding active peptides from the lectins of Bauhinia purpurea, lentil
      and Ulex europaeus have been synthesized by the solid synthesis method. The sugar
      binding activity of these peptides with neoglycoproteins and di/trisaccharides
      was observed by capillary electrophoresis, showing relative specificity.

PMID- 12237693
TI  - Studies on the Expression of Recombinant Human MCAF/GM-CSF Fusion Protein and Its
      Biological Activities.
AB  - With PCR technology and methods of DNA recombination in vitro, the fusion protein
      of GM-CSF with MCAF, the facto that has a directing effect on cells to a target,
      was generated by the construction of recombinant plasmids pMG 01, pMG 02 and pMG
      03 with different nucleotide composition between its SD sequence and the
      initiation codon ATG under the control of lambdaP(R) P(L) promoter of vector pBV
      220. Although no stable secondary structure exist in the translation initiation
      regions of all the recombinant plasmid constructed, the expression levels of the
      products with DH5 alpha (pMG 02) and DH5alpha (pMG 03) are much higher than that
      with DH5alpha (pMG01) which hardly expressed the product. The assay of Western
      blot indicated that the expressed product reacted with MCAF and GM-CSF
      antibodies, respectively. The assay of biological activities showed that the
      expressed product had apparent monocyte chemoattractant activity and supported
      the growth of the human GM-CSF-dependent cell line TF1, suggesting that the
      biological functions of MCAF and GM-CSF are compatible

PMID- 12237695
TI  - The Pellucida Glycoprotein ZP 3-Binding Protein of the Boar Spermatozoa.
AB  - Four protein components have been isolated from the CHAPS extract of boar
      spermatozoa by chromatography on PSL-Sepharose affinity column and cellulose CM
      52 ion exchange column sequentially. Both boar sperm protein SP1and SP2 exhibited
      binding activity with the zona pellucida glycoprotein ZP3 by immobilized zona
      pellucida glycoprotein binding assay (IZPGBA), and SP2 also showed
      hemagglutinating activity. The protein SP1 obviously inhibited sperm-oocyte
      binding when it was preincubated with oocytes. The inhibitory activity of SP1 was
      related to its concentration. By using Western blot technique and biotinylated
      ZP3, a Zp3-binding spermatozoa protein with molecular weight of 68 kD was
      identified, which may be a protein involved in sperm-oocyte binding.

PMID- 12237694
TI  - Comparative Studies on the Functions and Characteristics of the Glycosylated, the
      Nonglycosylated and the Recombinant PAI-1.
AB  - Glycosylated and nonglycosylated forms of PAI-1 were separated from HepG 2 cell
      by immunoaffinity chromatography with anti-PAI-1 monoclonal antibody, and the
      recombinant PAI-1 were purified from the media of expressed bacteria line of
      pYZhBI-66. Some functions and characteristics of the three PAI-1 were compared,
      such as the inhibiting effect on tPA, the activation by denaturation, the
      stability to thermal or pH changes, and the activation by fibrinogen and heparin.
      The results emphasized the roles of the oligosaccharide.

PMID- 12237696
TI  - Studies on the Effect of Recombinant Human Tumor Necrosis Factor-alpha on
      Leukemic Cell Lines by (31)P-NMR.
AB  - 31P nuclear magnetic resonance (NMR) spectroscopy has been used for monitoring
      cellular metabolism in human lymphoma cell line Molt-4 and human promyelocyte
      leukemia cell line HL-60. (31)P-NMR spectra of Molt-4 cells and HL-60 cells
      consist primarily of peaks of phosphomonoesters, inorganic phosphate (Pi),
      diphosphodiesters and ATP. A decrease in the ATP/Pi ration occurred after
      treatment of the Molt-4 cells with recombinant human tumor necrosis factor
      alpha(rhTHF-alpha). The ATP decreased after treatment of the Hl-60 cells with
      rhTNF-alpha.

PMID- 12237697
TI  - Studies on the synthesis and Antithrombosis Activity of the Analogue of Fibrin
      Decomposed Product-Related Peptide.
AB  - HPA of 85.5% purity was synthesized by the solid phase method on HPLC. The data
      obtained from amino acid analysis and fast atom bombardment were in good
      agreement with the theoretical values. The studies on the biological activity
      demonstrated the peptide inhibited efficiently the in vitro ADP-induced human
      platelet aggregation. In vivo, the peptide increased evidently the activity of
      plasmin and inhibited experimental thrombosis in the rabbit.

PMID- 12237698
TI  - The Application of Monoclonal Antibodies to the Imunoaffinity Purification of
      Human Ferritin.
AB  - There was difference between the reactivities of anti-human ferritin monoclonal
      antibodies, 6D6 and A-hF-C with liver and heart ferritins. 6D6 reacts with liver
      and heart ferritin with similar intensity, while A-hF-C reacts preferentially
      with liver ferritin. Two affinity gels were made with 6D6 and A-hF-C
      respectively, and used to purify ferritins from crude extracts of human liver and
      heart ferritins. The results have showed that it is a simple and time-saving
      method for the purification of ferritin with high purity and yield.

PMID- 12237699
TI  - Cloning and Expression of the rpoH Gene from Escherichia coli and Its Product
      Purification.
AB  - The rpoH gene, encoding the heat shock protein transcription factor sigma(32),
      was obtained by PCR and cloned into plasmid pUHE with the tac promoter. Upon
      induction with IPTG, it directed the expression of sigma(32) tailed with six
      additional histidine residues at its C-terminus. The histidine-tagged sigma(32)
      was purified with nickel-iminodiacetic acid affinity chromatography. Using (35)S
      radiolabeling methods in vivo, we found that even at low temperature the
      expression of sigma(32)-6 His may markedly increase the synthesis of the heat
      shock proteins such as GroEL, Dnak, and HtpH.

PMID- 12237700
TI  - The Expression of HCG Epitope Fused to Hepatits B Virus Core Antigen.
AB  - The DNA fragments encoding HGC-beta-37-CTP was amplified by PCR and fused to the
      core gene of HBV at the position of amino Acid 1(N-terminal fusion, pCn-HCG),
      154(C-terminal fusion, pCc-HCG), 75-83(internal fusion,pCm-HCG), and both 75-83
      and 154 (pC-HCG2) respectively. The fused genes were expressed in E. coli, and
      the antigenicity of both HBcAg and HCG as well as the expression level were
      analyzed. In addition, the chimeric particular characteristics of the proteins
      and their immunogenicity were identified. It revealed that the fusion proteins
      pCm-HCG and pCc-HCG were able to form particles, and that the fusion protein pCm
      HCG could induce antibody of anti-HCG of high titers in mice, suggesting that the
      position at 75-83 amino acid residue should be a relatively promising fusion site
      for HCG.

PMID- 12237701
TI  - Studies on the Stimulating Nature of Uncouplers on the Electron Transport in BBY
      Particles.
AB  - BBY particles, which have kept the physicochemical property of PSII, were shown
      by transmission electron microscopy to possess no intact thylakoid membranes. The
      results of measuring 9-AA fluorescence quenching and millisecond Chl alpha
      delayed light emission proved that BBY particles were also unable to establish
      proton gradient across the membranes (deltapH) in light. Moreover, uncouplers
      gramicidin D and NH(4)Cl increased PSII electron transport in BBY particles only
      at low pH. This stimulation was more obvious around pH 6.0 than at other pH. The
      consistent stimulating value and pH-dependence indicated that the stimulating
      mechanisms of the two uncouplers are similar. From above, we infer that the
      uncouplers can bypass the proton transfer of localized pathway in BBY particles,
      stimulating the corresponding electron transport.

PMID- 12237702
TI  - Pyocyanine Promoted the Photoreduction of Cytochrome b-559 in Chloroplasts.
AB  - A light-induced absorbance increase at 559 nm was observed in spinach
      chloroplasts in the presence of pyocyanine. The reaction was induced by red light
      (650 nm) but not by far-red light (720 nm). The light-dark difference spectra
      indicated that the reduced component was cytochrome b-559. The effect of
      pyocyanine was nearly saturated at a concentration of 1 &mgr;M and was
      independent of the transmembrane proton gradient. The pyocyanine-promoted
      photoreduction of cytochrome b-559 was inhibited by DCMU and DBMIB. In cyanide
      poisoned chloroplasts pyocyanine still promoted the photoreduction of cytochrome
      b-559. In chloroplasts treated with CCCP the oxidation of cytochrome b-559 can be
      induced by red light of low intensity. Pyocyanine reversed the effects of CCCP so
      as to promote the reduction of cytochrome b-559 by red light of both high and low
      intensities. We assumed that pyocyanine affected the light-induced redox reaction
      of cytochrome b-559 by affecting the protonation of the cytochrome.

PMID- 12237703
TI  - Purification and Characterization of Phospholipase A(2) from the Venom of Snake
      Trimeresurus stejnegeri Schmidt.
AB  - A phospholipase A(2)(PLA(2)) was purified from the venom of the snake
      Trimeresurus stejnegeri Schmidt by Sephadex G-75 gel filtration, Mono Q ion
      exchange chromatography and Superose-12 gel filtration with FPLC and proved to be
      homogeneous as shown in SDS-PAGE and IEF. Its molecular weight is around 18 000
      and isoelectric point is 4.7. Amino acid composition of PLA(2) was determined.
      Apart from hydrolyzing phosphatidylcholine, the enzyme has a potent inhibitory
      effect on platelet aggregation induced by ADP or collagen with half-inhibitory
      concentration of 10-15 &mgr;g/ml and 50-80 &mgr;g/ml respectively.

PMID- 12237704
TI  - The crystallization and Preliminary Crystallographic Analysis of the Monoclinic
      Crystal Form of Basic Phospholipase A(2) from the Venom of Agkistrodon halys
      Pallas.
AB  - The basic phospholipase A(2) from the venom of Agkistrodon halys Pallas exhibits
      strong hemolytic activity. The enzyme has been crystallized by vapour diffusion
      techniques. Diffraction data of the crystal have been collected up to 2.5 Aring;
      resolution using the synchrotron radiation-imaging plate-Weissenberg camera
      system. The crystal parameters were calculated with an auto-indexing program. The
      crystal belongs to C2 space group with unit cell dimensions of alpha=100.38
      Aring;, b=54.37 Aring;, c=117.38 Aring; and beta=120.71 deg;. Each asymmetric
      unit probably contains four or five molecules.

PMID- 12237705
TI  - The Distributive Study of Plasmalogen in Guinea Pig Tissues.
AB  - The content of plasmalogen and plasmenylethanolamine (PE-plasmalogen) in the
      guinea pig brain, heart, liver, lung, kidney and muscle were examined and compare
      to the total phospholipids and total phosphatidylethanolamine (PE) of these
      organs, by the methods of Gottfried iodine and thin layer chromatography. The
      highest content of plasmalogen and PE-plasmalogen was found in the brain, which
      was 9.28 and 6.54 &mgr;mol/g of tissue respectively, followed was in the heart
      which was 5.29 and 2.01 &mgr;mol/g of tissue respectively. The lowest content of
      plasmalogen and PE-plasmalogen was in the liver, which was 1.47 and 0.67
      &mgr;mol/g of tissue respectively. It was also found that the content of PE
      plasmalogen in the muscle of the guinea pig was higher than that in the kidney,
      lung and liver, it accounts for 40.1% of the total PE. The distributing
      regularity and biological significance of plasmalogen in guinea pig tissues were
      discussed.

PMID- 12237707
TI  - Studies on the Peroxidation of Polyunsaturated Fatty Acid from Lipoprotein
      Induced by Iron and The evaluation of The Anti-oxidative Activity of Some Natural
      Products.
AB  - Studies on the peroxidation of polyunsaturated fatty acid from yolk lipoprotein
      induced by iron was curried out. A comparison of the experimental conditions for
      the model system of peroxidation was made. The system was successfully applied to
      determine the activity of the anti-oxidative activity of some effective
      ingredients of Chinese traditional medicine.

PMID- 12237706
TI  - Expression of the Gene Encoding Diapause Hormone and Pheromone Biosynthesis
      Activating Neuropeptide During Post-embryonic Development in the Silkworm, Bombyx
      mori.
AB  - Embryonic diapause and sex pheromone biosynthesis in the silkworm, Bombyx mori,
      are induced by the diapause hormone (DH) and the pheromone biosynthesis
      activating neuropeptide (PBAN), respectively. These are produced in the
      suboesophageal ganglion from a common polyprotein precursor (DH-PBAN precursor)
      encoded in a single gene (DH-PBAN gene). Using RT-PCR and Southern hybridization
      methods, we quantitatively measured DH-PBAN mRNA content throughout the post
      embryonic development. The results show that DH-PBAN gene not only expresses
      during pupal stage, but also during larval and adult stages. The high level of
      expression during pupal stage suggests that DH and PBAN are respectively
      synthesized.

PMID- 12237709
TI  - Expression of C-terminal Segment of Bone Morphogenetic Protein in E. coli.
AB  - Two recombinant C-terminal segments of human bone morphogenetic protein 2A
      (BMP2A), designated as BMP23 (173 aa) and BMP24 (134 aa), were expressed under
      the control of P(L) promoter in E. coli. SDS-PAGE analysis showed two induced
      protein bands at 20 kD and 15.5 kD, which were about 10% and 20% of the total
      bacterial protein, respectively. Both the expressed proteins were insoluble
      aggregates, which reached 80% purity after rapid preparation of the products as
      the inclusion body. The results of N-terminal amino acid sequencing showed that
      the first 15amino acids at the N-terminal were identical to those encoded by the
      cDNA genes of both BMP24. After refolding both BMP23 and BMP24 formed disulfide
      linked dimeric protein bands in SDS-PAGE. Bioassay in vivo revealed that BMP23
      induced chondrocytes differentiation and BMP24 stimulated collagen synthesis.

PMID- 12237708
TI  - Expression of the atpE Gene Coding for the epsilon Subunit of Maize Chloroplast
      Coupling Factor.
AB  - The entire atpE gene of the maize chloroplast coupling factor was inserted into
      the polylinker region of vectors pJLA505 and pWA to form recombinant plasmids
      pJLA505-atpE and pWA-atpE respectively. These expression plasmids were
      transformed into E. coli NM522 which induced at 42 degrees. By the analysis of
      SDS-PAGE, the expressed product of interest was observed to account fore more
      than 3o% of total E. coliproteins. The identification of the expressed product
      demonstrated that its immunological specificity was well retained. The antiserum
      cross-reacted with the expressed epsilon protein and CF(1)-epsilon protein of
      spinach and produced precipitin lines on Ouchterlony immunodiffusion test. The
      expressed product aggregated insolubly as the inclusion body and was purified to
      over 80% purity. The purified product had the same function as that of the native
      epsilon subunit.

PMID- 12237710
TI  - Analysis of the Damage Site to Oxyleghaemoglobin by H(2)O(2) on the Basis of the
      Changes in Absorption Spectra.
AB  - Leghaenoglobin (Lb) is a Fe-protein with a high content in the root nodules of
      soybean (Glycine max). Oxyleghaemoglobin (LbO(2), Fe(2+)-protein) prepared from
      fresh soybean root nodules in san active form of Lb. LbO(2) displays two distinct
      absorption bands at 577 nm and 540 nm, which are closely related to the structure
      of haem (iron-porphyrin). Another absorption band found at 280 nm is related to
      the configuration of the globin. When LbO(2) was incubated with H(2)O(2), prompt
      changes in visible-absorption spectra appeared and the UV-absorption spectra was
      relatively stable. We conclude that the position of damage by H(2)O(2) was
      located on the Fe(2+)-porphyrin ring rather than in the globin of LbO(2).

PMID- 12237711
TI  - Studies on the Correlation of the TATA-box Binding Proteins of the Rat PSBP C(3)
      Gene with Its Transcription Activities.
AB  - The transcription of the rat C(3)(1) gene is markedly stimulated by testosterone
      and is confined to the ventral prostate (V.P.). The potential correlation of the
      TATA-box binding proteins of the C(3) gene with its highly tissue-specific and
      androgen-controlled expression was investigated by using electrophoresis mobility
      shifting assay (EMSA) and in vitro DNaseI footprinting analysis. The results
      showed that the nuclear proteins bound on the 40 bp C(3)(1) TATA-box DNA fragment
      (-50 to -10) appeared in a highly tissue-specific manner. By comparing the
      protein binding activities of the C(3)(1) probes with a silent allelic form
      C(3)(2) probe which shared sequence homology with only one bp difference in the
      TATA-box (A to G at -29), it was found that the loss of binding activity occurred
      only in the V.P. which expresses C(3) gene when A was replaced by G at -29. This
      finding indicated that the specific -29(A)-dependent binding proteins of the V.P.
      may have additional domains which facilitate the binding of androgen receptor or
      other cofactors involved in androgen regulation of C(3) expression.

PMID- 12237712
TI  - Sequencing and Structural Analysis of a Novel Early-late Gene of the Leucania
      separata Nuclear Polyhedrosis Virus.

PMID- 12237713
TI  - SOD-like Activity of Copper Salicylate Complex in Tween Micellar Systems.
AB  - Copper salicylate-ethanol complex was synthesized and its composition was
      analysed. The four surfactants (Tween-20, Tween-40, Tween-60, Tween-80) were
      purified. Their critical micelle concentrations (CMC) in phosphate buffer
      (pH=7.4) were measured. The SOD-like activity of copper salicylate complex was
      assayed using the cytochrome-c reduction method. The scavenging effects of the
      four surfactants on O(2)(-). and.OH were investigated. The cooperative effect of
      the complex with surfactants and micelles was studied in detail. An activity
      enhancement of the complex was observed in the presence of surfactants. The four
      surfactants themselves display SOD-like activities to a certain extent. It was
      shown that the complex and the four surfactants have apparently positive
      cooperative actions and similar results were obtained in the experiment for anti
      lipid peroxidation of red cell membrane. These results might be explained by the
      fact of micellar catalysis and the copper salicylate-Tween system was suggested
      to be used as anti-inflammatory drugs.

PMID- 12237714
TI  - The Tissue Distribution of a New Androgen Inducible Cytosol Protein.
AB  - As a preliminary but important step in the investigation of the function of the
      new androgen-dependent DNA binding cytosol protein (C(3)P(4)) discovered by using
      gel retardation assay with a 31 bp fragment of DNA of the promoter of the rat
      ventral prostatic binding protein (PSBP) C(3) gene as a probe, a general survey
      was carried out on the tissue distribution of this protein in rat mice, rabbit
      and monkey of both sexes and also in some human pathological tissues with the
      following findings: (1) C(3)P(4) is present in all the male sex organs in
      different amount, but none in female sex organs. (2) C(3)P(4) has been found in
      the brain of all the species studied. (3) Its occurrence in other tissues are
      rare and show species variation, but no sex difference. (4) Of the samples
      collected from 8 different human pathological tissues, stomach cancer, both
      benign and malignant mammary tumors and three of the benign prostatic hyperplasia
      tissues revealed certain changes, the potential significance of these findings
      were discussed.

PMID- 12237715
TI  - Overexpression of a Novel Highly Active Tumor Necrosis Factor Mutant in E. coli.
AB  - A synthetic gene of human tumor necrosis factor alpha (hTNF-alpha) was mutated by
      polymerase chain reaction using a multi-site mutated primer with the Arg-2 codon
      (CGT) replaced by a lysine codon (AAA). The mutated gene was inserted into vector
      pSB-92 at the downstream of P(L) promoter to give a recombinant plasmid pBS-TNF
      K2 and expressed in E. coli. Soluble [Lys(2)] hTNF-alpha mutein was obtained in
      high yield, accounting for more than 60% of the total cellular protein and easy
      to purify. Compared to the wild type hTNF-alpha, purified [Lys(2)] hTNF-alpha has
      slightly less toxicity but shows tens to hundreds times greater inhibitory
      activity to several human tumor cell lines.

PMID- 12237716
TI  - Purification and Characterization of EGF-like Active Peptide from Calf
      Submaxillary Gland (c-EGF).
AB  - A peptide with M(r) of 6 kD and pI at 4.6 was purified from calf submaxillary
      gland by acid extraction, CM52 and DE52 ion exchange chromatography, Sephadex G
      75 gel filtration and HPLC. Similar to rh- EGF, the peptide has such biological
      effects as the stimulation of the proliferation of NRK cells and fetal epithelial
      cells in vitro, the acceleration of incisor eruption and eyelid opening in new
      born mice and the stimulation of phosphorylation of the membrane protein of A 431
      cells. The amino acid composition of this peptide is similar to that of rh-EGF,
      with both deficient in phenylalanine and threonine.

PMID- 12237717
TI  - The Influence of Amino Acid Substitutions on the Function of Interleukin-2.
AB  - The effects of some residues in IL-2 on its activity have been studied by site
      directed mutagenesis. After changing 39 Met or 43 Lys to Pro, neither the CD
      spectra (s) nor the biological activities of these mutants were changed, implying
      that the 39 Met and 43 Lys were not involved in the reported alpha-helical
      structure. However after changing 52 Glu, 53 Leu or 54 Lys to Pro respectively
      the CD spectra were markedly changed and the activities were decreased
      significantly, showing that these three amino acids in IL-2 were integrated in
      the alpha-helix structure and very important for their biological functions. The
      significance of the above results was discussed.

PMID- 12237718
TI  - The Purification and Renaturation of the Interleukin-2-Pseudomonas Exotoxin
      Fusion Protein (IL-2-PE).
AB  - The IL-2-PE fusion protein expressed in E. coli forms the inclusion body which
      can be isolated easily. The purity of the fusion protein was 90%-95% after
      washing the inclusion body with PBS containing 4 M urea and 0.5% Triton X-100
      followed by chromatography on Sephacryl S-300 and DEAE-Sepharose FF. Then,
      parameters relative to the renaturation, including the concentrations of GSSG and
      L-Arg, the initiation concentrations of the protein, pH, temperature and Reaction
      time etc, were systematically analysed. An optimum condition for IL-2-PE
      renaturation was proposed.

PMID- 12237719
TI  - Purification and Characterization of a DTT-sensitive Protease Associated with PS
      II Particles.
AB  - A DTT-sensitive protease was purified by hydrophobic chromatography on butyl
      Toyopearl 650 M and anion-exchange chromatography on DEAE-Sephadex A-50 from the
      1 M NaCl extract of PS II particles. The results of SDS-PAGE and gel-filtration
      chromatography on Superose 12 Have showed that it is a monomeric protease with a
      MW of 37 000. The protease generated polypeptides of 13.2 kD, 12 kD and 10.5 kD
      fragments from 18 kD protein, and those of 23 kD, 22 kD and 20 kD fragments from
      24 kD protein, respectively. The protease had maximum activity at pH 8.0, and
      showed to be sensitive to DTT and beta-Me but insensitive to the ionic strength
      of NaCl. Studies with protease inhibitors suggested that this enzyme is not a
      serine-protease.

PMID- 12237720
TI  - Preparation and Characterization of Superoxide Dismutase Soluble in Organic
      Solvents.
AB  - A glycolipid (2C(12)GE) is synthesized with glutamate, dodecanol and
      gluconolactone and a glycolipid-coated superoxide dismutase (SOD) is prepared by
      mixing an aqueous solution of the enzyme with the synthetic 2C(12)GE. The
      glycolipid-enzyme complex (SOD-2C(12)GE) is insoluble in water but soluble in
      organic solvents such as ethanol, acetone, glycerin and dioxane. It exhibits a
      higher activity in some organic solvents such as ethanol than in water and there
      is an optimum concentration in organic solvent for the catalytic reaction. The
      SOD-2C(12)GE is more stable against changes in temperature, pH and hydrolysis by
      protease than the native SOD.

PMID- 12237721
TI  - The Effect of 54 kD Calcium-binding Protein on the Platelet Membrane-bound
      PLA(2).
AB  - A 54 kD calcium-binding protein was isolated form porcine platelet after calcium
      precipitation and chromatography. Its calcium-blinding ability was proved by the
      Arasenzo III binding analysis. In order to study the physiology role of calcium
      binding protein in platelets, an experiment to study the effect of 54 kD calcium
      binding protein on the platelet membrane-bound PLA(2) was designed. We isolated
      porcine platelet membrane by the two-phases system and developed a simple assay
      method for phospholipase A(2) by the colorimetric micro-determination of long
      chain fatty acid released by the enzyme. The results indicated that in the
      presence of 54 kD CaBP the activity of porcine platelet membrane-bound PLA(2) was
      stimulated with lower Ca(2+) concentration (<1 mM), but inhibited when the Ca(2+)
      concentration was above 1 mM. The inhibiting effect of 54 kD CaBP was not
      decreased with the increase of substrate concentration.

PMID- 12237722
TI  - Purification and Studies of Some Properties of Pig-kidney Biliverdin Reductase.
AB  - Biliverdin reducatase was purified from pig-kidney to homogeneous form through
      DEAE 52-cellulose, Sephadex G-100 and Procion red HE 3B-Sepharose 4B column
      chromatography, The enzyme was estimated to be a monomer with a molecular weight
      of 66kD by SDS-PAGE. A gel staining in basic-pyridine solution of heme was used
      to identify purified biliverdin reductase. The enzyme utilized NADPH and NADH as
      electron donors for the reduction of biliverdin to produce bilirubin. The
      apparent K(m) values for biliverdin were established to be 1.25 &mgr;M with NADPH
      and 2.52 &mgr;M with NADH.

PMID- 12237723
TI  - Enhancing and Inhibiting Effect of Vitamin C on Lipid Peroxidation in the
      Linoleic Acid Micelle System.
AB  - Vitamin C (Vc), a reductant in the body can function as an antioxidant by
      scavenging free radicals. However, with the coexistence of the transition metal
      iron (Fe), Vc can induce lipid peroxidation reaction resulting in the production
      of conjugated diene which has a peek absorbance at UV 234 nm. In order to clarify
      the proportion of Vc to Fe on the two different effects mentioned above, the
      authors detected conjugated diene production by means of spectrophotometer in
      linoleic acid micelles induced by Fe with different amount of Vc. The results
      showed that in the presence of Te or Vc alone there was no induction of lipid
      peroxidation. In the presence of some Fe (20 &mgr;M), Vc induced lipid
      peroxidation at a concentration of 80 &mgr;M or lower, but inhibited lipid
      peroxidation at concentration of 100 &mgr;M or higher. The pH of the experimental
      system clearly affected the lipid peroxidation induced by Fe-Vc, with the
      production of conjugated diene at acidic pH, but none at physiological pH.

PMID- 12237724
TI  - Comparison of the Inhibitory Effects of Quercetin and Rutin on the Oxidative
      Modification of LDL induced By Fe(2+)Cu(2+).
AB  - Using the oxidative modification of low density lipoprotein (LDL) as a model and
      the content of thiobabituric acid reactive substances (TBARS) s an index, the
      inhibitory effects of quercetin and rutin on oxidative modification of LDL
      induced by Fe(2+) and Cu(2+) were compared. The results showed that the rates of
      oxidative modification of LDL induced by Fe(2+) and Cu(2+) were similar in 0.15
      mM NaCl (pH 7.4). The inhibitory action of quercetin on the oxidative
      modification of LDL induced by Cu(2+) was slightly more effective than in the
      case of induction by Fe(2+), and the action of rutin on the oxidation
      modification induced by Fe(2+) was significantly more effective than in the case
      of induction by Cu(2+).

PMID- 12237726
TI  - Restricting physician prescribing.

PMID- 12237725
TI  - Preparation of Neoglycoproteins by Using Homo-bifunctional Reagent as the
      Coupling Agent.
AB  - Several neoglycoproteins (Man-BSA, Gal-BSA, Glc-BSA, Lac-BSA, GlcNAc-BSA, Fuc-BSA
      and Rha-BSA) have been prepared by using homo-bifunctional reagents (divinyl
      sulfone, DVS and 1,4-butanediol diglycidyl ether, Epoxy) as coupling agents and
      purilied with the respective immobilized lectins (except Fuc-BSA and Rha-BSA).
      These purified neoglycoproteins showed binding specificity to the corresponding
      lectins by hemagglutinating inhibition test and double diffusion experiment.

PMID- 12237727
TI  - A revolution in transfusion medication in the last decade.

PMID- 12237728
TI  - Perioperative use of erythropoietin.
AB  - Erythropoietin (EPO) is the primary regulator of red blood cell (RBC) production,
      and hypoxia is the main stimulus for EPO secretion. Increases in circulating
      levels of EPO are proportionate to the levels of tissue hypoxia, which are
      influenced by hematocrit (HCT). Small decreases in HCT as would be typical after
      presurgical autologous blood donation often do not result in increased EPO levels
      or in compensatory erythropoiesis. Erythropoiesis may also be limited by
      deficiencies of vitamin B(12), folate, and, most commonly, iron. The preoperative
      administration of EPO is effective in increasing erythrocyte mass and autologous
      donation volumes while maintaining higher HCT levels. In some surgical
      populations, particularly those individuals who experience surgical blood losses
      in excess of 2 L, EPO treatment also reduces allogeneic blood exposure. This
      effect is prominent in patients with a low initial HCT. Current assessments of
      the cost-effectiveness of EPO suggest that it achieves little overall improvement
      in patient health and that what improvement it does offer, it does at enormous
      cost.

PMID- 12237729
TI  - Safety and efficacy of methods for reducing perioperative allogeneic transfusion:
      a critical review of the literature.
AB  - A number of pharmacologic and nonpharmacologic technologies are in current use to
      minimize perioperative homologous blood use. Clinical trials, many of them
      randomized controlled trials, have been done evaluating these approaches and have
      demonstrated their efficacy. However, data on safety has relied mostly on case
      reports, uncontrolled studies, and, for the pharmacologic agents, extrapolation
      from the nonsurgical setting. In this review I analyze the data from the
      randomized trials and the lower-level evidence studies to provide the best
      estimates in safety with these alternatives. In general, these alternatives are
      safe with proper dosing and monitoring of effects. With aprotinin, the primary
      concern is anaphylaxis, and this predominantly with re-exposure. With aprotinin
      and with the anti-fibrinolytics, increased venous thromboembolic risk has not
      been a consistent finding. Tranexamic acid use intraoperatively is advantageous,
      but postoperative use appears to have no advantage and may be associated with
      renal dysfunction. DDAVP is low-risk, provided it is not overused, which can
      induce hyponatremia. Autologous predonation probably has similar risks as
      homologous blood with respect to transfusion errors and bacterial infection. As
      with most medical interventions, we must be vigilant to prevent human error.

PMID- 12237730
TI  - Immunomodulation and blood transfusion.
AB  - Over the past three decades, evidence from a variety of sources has suggested
      that allogeneic blood transfusions can induce clinically significant
      immunosuppression in recipients. This clinical syndrome is referred to in the
      transfusion medicine literature as transfusion-associated immunomodulation (TRIM)
      and has been linked to an improved clinical outcome in the setting of renal
      transplantation. Possible deleterious TRIM-associated effects include increased
      prevalence of cancer recurrence and postoperative bacterial infections. The
      recognition that TRIM can increase morbidity and mortality in allogeneically
      transfused individuals has become a major concern for those involved in
      transfusion medicine. Whether TRIM predisposes recipients to increased risk for
      cancer recurrence and/or bacterial infections is still not proven, however. In
      contrast to the available clinical data, studies in experimental animal models
      suggest that TRIM is an immunologically mediated biologic effect associated with
      the infusion of allogeneic leukocytes, which can be ameliorated by prestorage
      leukoreduction. Although considerable data have been accumulated in an attempt to
      unravel the clinically adverse effects of TRIM, the precise mechanism of TRIM has
      yet to be elucidated. Further studies, both basic and applied, to establish the
      clinically relevant manifestations of TRIM as well as the mechanism(s) are
      urgently required.

PMID- 12237731
TI  - Perioperative blood transfusion therapy in pediatric patients.
AB  - In general, transfusion guidelines for non-neonatal pediatric patients are
      similar to those for adults. However, some differences do exist and certain
      precautions may be necessary particularly in the setting of massive transfusions.
      We review these differences as they apply to general pediatric surgery outside of
      the neonatal period, with respect to the transfusion of red blood cells (RBCs),
      platelets, fresh-frozen plasma (FFP), and cryoprecipitate. We include a
      discussion of the indications for transfusion and practical considerations such
      as dosing and administration. Finally, we briefly review the use of directed
      donations and specialized (irradiated, CMV seronegative) blood components.

PMID- 12237732
TI  - Blood donor selection and screening: strategies to reduce recipient risk.
AB  - Various measures are taken to ensure the safety of the blood supply. Donor
      selection begins with education of the public about transfusion-transmissible
      diseases. Potential donors must answer a questionnaire designed to identify
      specific risk factors for these infections. The questionnaire is the only line of
      protection against certain infections for which no testing is performed, such as
      malaria, babesiosis, leishmaniasis, and Chagas disease. All donations are tested
      for the presence of antibodies to HIV-1 and -2, HCV, HTLV and syphilis, the
      hepatitis B surface antigen (HbsAg), the p24 antigen (HIV), and also for HIV and
      HCV nucleic acids. The introduction of new and improved screening tests for
      transfusion-transmissible diseases has led to remarkable improvement in the
      safety of the blood supply, with substantial shortening of the window period for
      HIV, HCV, and HBV infections. The current challenge of the industry is to reduce
      even further the small but significant risk of bacterial contamination of
      platelet components. Finally, some safety measures are purely precautionary, such
      as the deferral of donors who have traveled to certain countries affected by the
      bovine spongiform encephalopathy (BSE).

PMID- 12237733
TI  - Re-evaluating the transfusion trigger: how low is safe?
AB  - Concerns about transfusion-associated complications, in particular viral
      transmission, have motivated a more restrained pattern of clinical transfusion
      practice. This change in practice has allowed for an evaluation of the risks of
      withholding transfusion and the benefits of providing transfusion. The recognized
      risks of transfusion have declined, and this reduction in risks has been brought
      about by improved screening, better testing strategies and tests, and leuko
      reduction at the time of donation. There are benefits to transfusion, in limiting
      hypoxic morbidity and mortality. These benefits are clearly evident only at very
      low levels of serum hemoglobin concentrations in healthy patients who tolerate
      moderate levels of anemia without morbidity. However, the benefits of transfusion
      are apparent at higher initial serum level concentrations in patients with
      cardiovascular disease who are less tolerant of anemia.

PMID- 12237734
TI  - Blood transfusions and the Jehovah's Witness patient.
AB  - This paper provides a brief history of the evolution of the Jehovah's Witness
      faith with a short discussion on the biblical justification for followers'
      refusal of blood transfusions. It also briefly considers the ethical principles
      leading to potential conflicts between health care workers and Jehovah's
      Witnesses patients and examines several significant legal rulings in the United
      States and Canada that caregivers should be aware of. A discussion of what blood
      products are and are not currently acceptable is also presented. Finally, the
      impact of the Jehovah's Witness reform movement aimed at allowing blood
      transfusions and the nature of recent doctrinal shifts in the Jehovah's Witness
      faith on the matter of blood transfusions are discussed.

PMID- 12237735
TI  - Changes in circulating blood and plasma volume after hemoglobin-based oxygen
      carrier infusion and additional infusion of colloid solutions.
AB  - The aim of this study was to investigate the changes in circulating blood volume
      (CBV) after infusions of Hemoglobin glutamer-200 (bovine; Hb-200) in combination
      with 6% hetastarch in an animal model of acute posthemorrhagic anemia. Fifteen
      rabbits with a mean body weight of 2.2 +/- 0.2 kg were studied. After
      determination of the circulating plasma volume (CPV) and CBV, one third of the
      CBV was withdrawn via an arterial catheter. An equal volume of Hb-200 was then
      infused in the 5 animals in study group 1. In the remaining 10 animals, the same
      volume of 6% hetastarch solution was infused. Fifteen minutes after completion of
      the infusion, an additional infusion of 6% hetastarch at a dose equal to one
      third of the baseline CBV was performed in study group 1 and the control group.
      In study group 2, equal volumes of Hb-200 were infused. CPV measurements were
      performed at baseline, after hemorrhage, 5 and 15 minutes after volume
      replacement, and 1 and 15 minutes after hypervolemic hemodilution using the Evans
      blue dye dilution technique. The mean baseline CPV value was 53.4 +/- 1.1 mL/kg.
      The mean CBV at baseline was 90.8 +/- 4.9 mL/kg. After one third of the CBV was
      withdrawn, no differences in CBV or CPV were observed between the three groups.
      Replacement of one third of the CBV with Hb-200 significantly increased the CPV
      (73.7 +/- 1.8 mL/kg) when compared with the baseline level (53.5 +/- 1.8 mL/kg; n
      = 5; P < 0.05). The difference between the groups was first observed 15 minutes
      after infusion. CPV was significantly higher in study group 1 (87.0 +/- 2.2
      mL/kg) compared with the other groups (80.2 +/- 2.6 mL/kg in the control group
      and 79.5 +/- 3.6 mL/kg in study group 2). After a second transfusion, the
      differences between the groups became more prominent. Study group 2 demonstrated
      the highest CPV and CBV. The two study groups demonstrated a statistically
      significant increase in circulating volumes compared with the control group. The
      magnitude of this difference was lower than expected based on in vitro colloid
      osmotic pressure measurements.

PMID- 12237736
TI  - Effects of hemoglobin glutamer-250 (bovine) (HBOC-201, Hemopure) on coagulation
      testing.
AB  - Polymerized bovine hemoglobin is currently under investigation as an alternative
      to blood-banked human red blood cells. Because of the dark red hemolyzed
      appearance of hemoglobin-based oxygen carrier (HBOC)-201, we sought to describe
      the effects of HBOC-201 on coagulation analyzers that perform prothrombin times,
      activated partial thromboplastin times, fibrinogen, and antithrombin. Pooled
      normal plasma was combined with HBOC-201 to achieve plasma hemoglobin levels of
      1.4, 2.6, 3.8, 4.8, and 6.2 g/dL. Results for each test using HBOC-201-prepared
      plasma were compared with results using saline-matched controls. Two consecutive
      absolute result differences of >10% between saline controls and HBOC-201 samples
      were used for determining interference in test accuracy by the concentration of
      HBOC-201. Mechanical detection methods (fibrometer, STA, CS-190) and the MDA-180
      method were less affected by increasing levels of HBOC-201 than optical detection
      devices for all test parameters.

PMID- 12237737
TI  - Blood substitutes and oxygen therapeutics: an overview and current status.
AB  - This review article discusses the development and implementation of a number of
      blood substitutes, including hemoglobin-based oxygen carriers (HBOCs) and
      perfluorocarbons. This review article will introduce the reader to blood
      substitutes by discussing an overview of an ideal blood substitute, the history
      of HBOCs and perfluorocarbons, strategies of oxygen carrying, side effects of
      HBOCs and perfluorocarbons, current clinical trials, and the future of blood
      substitutes.

PMID- 12237738
TI  - A randomized, double-blind comparison of 10 and 20 mg lercanidipine in patients
      with stable effort angina: effects on myocardial ischemia and heart rate
      variability.
AB  - We evaluated the anti-ischemic action and the effects on autonomic function of
      lercanidipine, a long-acting dihydropyridine calcium antagonist, in 25 patients
      with stable effort angina in a randomized, double-blind, parallel trial. After a
      2-week placebo run-in period, patients entered a 2-week treatment period with 10
      or 20 mg of lercanidipine once daily. During the placebo run-in period and at the
      study end, the patients underwent clinical examination, electrocardiography,
      exercise tests, 24-hour Holter electrocardiography for long-term heart rate
      variability evaluation, and short-term spectral analysis of heart rate and
      systolic blood pressure variability and plasma epinephrine and norepinephrine
      levels at rest and during tilting. Results showed that time to onset of ST
      segment depression > or =1 mm was significantly increased by both drug doses. No
      significant change was recorded in the average hourly heart rate after treatment
      with both 10 and 20 mg of lercanidipine. During the 24-hour recordings, no
      significant change was observed in low-frequency power, high-frequency power, or
      low frequency/high frequency. In the standing position, there was a significant
      increase in plasma norepinephrine and epinephrine concentration in both groups,
      and no change in the supine position after 10 and 20 mg of lercanidipine. When
      considering short-term heart rate variability, no significant difference was
      observed in either treatment group in low frequency, high frequency, or their
      ratio on electrocardiographic R-R spectra. The blood pressure spectral component
      was also unchanged. In conclusion, lercanidipine is effective in reducing
      ischemia in patients with stable effort angina. Moreover, lercanidipine does not
      cause adrenergic activation, which is the main mechanism hypothesized to explain
      the negative effect on cardiovascular mortality assigned to short-acting
      dihydropyridine calcium antagonists.

PMID- 12237739
TI  - Adenosine 5'-triphosphate axis in obstructive airway diseases.
AB  - In recent years, significant progress has been made in our understanding of the
      pathophysiology behind obstructive airway diseases in general and asthma in
      particular; this knowledge, however, has not translated to major breakthroughs in
      the treatment of these disorders. Current therapeutic options are less than
      optimal and frequently are associated with systemic adverse effects. Recent
      studies indicate that endogenous purine nucleotides, adenosine 5'-triphosphate
      (ATP) in particular, could play a mechanistic role in obstructive airway diseases
      through their actions on multiple cell types relevant to these disorders,
      including mast cells, eosinophils, dendritic cells, and neurons. The
      pharmacologic modulation of ATP signal transduction in these cells represents an
      attractive new therapeutic target.

PMID- 12237740
TI  - Current therapy for Behcet's disease.
AB  - Classified among the vasculitides, the clinical spectrum of Behcet's disease (BD)
      ranges from a mild mucocutaneous disease to a life-threatening systemic
      vasculitis, characterized by remissions and recurrences. The major morbidity is
      recurrent eye inflammation that may lead to blindness, but severe central nervous
      system, gastrointestinal, or vascular involvement may occur and might be fatal.
      In contradistinction to most other vasculitides, the venous system is commonly
      affected in BD. The treatment of BD is usually symptomatic and palliative. This
      includes topical steroids for orogenital ulcers, nonsteroidal antiinflammatory
      agents for joint involvement, and colchicine as prophylaxis against disease
      flares (although evidence that colchicine prevents recurrences of oral and
      genital ulcers is restricted to female patients). Immunosuppressives and
      cytotoxic agents are used for more severe involvement, and thalidomide and
      interferon have attracted attention in recent years.

PMID- 12237741
TI  - Removal of the carboxy terminus of the A2A-adenosine receptor blunts constitutive
      activity: differential effect on cAMP accumulation and MAP kinase stimulation.
AB  - The A(2A)-adenosine receptor has an extended carboxy terminus (approximately 120
      amino acids), the role of which is poorly defined. In human endothelial cells and
      in HEK293 cells, the A(2A)-receptor controls at least two independent signalling
      pathways, i.e. increased cyclic adenosine 3',5'-monophosphate (cAMP) formation
      via its cognate G protein G(s) and increased phosphorylation of mitogen-activated
      protein kinase (MAP kinase) by recruiting p21(ras). In order to address the role
      of the carboxy terminus in signal transfer, we generated HEK293 cells that stably
      expressed the full-length (wt) receptor and truncated versions [A(2A)-R(1-360)
      and A(2A)-R(1-311)] at comparable levels (approximately 0.5 pmol/mg) in the
      plasma membrane. The effects of truncation were divergent with respect to the two
      effectors regulated by the receptor. In intact cells carrying A(2A)-R(wt) and
      A(2A)-R(1-360), cAMP accumulation was more potently activated by an A(2A)-agonist
      than in cells expressing A(2A)-R(1-311). Similarly, A(2A)-R(wt) and A(2A)-R(1
      360)--but not A(2A)-R(1-311)--caused constitutive (=agonist-independent)
      elevation of cAMP which was reversed by the addition of A(2A)-antagonists. In
      membranes prepared from these cells, however, the three receptors displayed no
      constitutive activity in stimulating adenylyl cyclase and they did not differ in
      apparent agonist affinity. Truncation of the A(2A)-receptor did also not decrease
      the potency of an A(2A)-agonist to stimulate MAP kinase in intact cells. We
      conclude that the carboxy terminus defines both (a) the level of constitutive
      activity, i.e. the equilibrium R<--> R*, in intact cells only, indicating a role
      for a component that is lost upon cell lysis, and (b) the efficiency of signal
      transfer in alternative pathways.

PMID- 12237742
TI  - Mechanism of inhibitory action of ethanol on inducible nitric oxide synthesis in
      macrophages.
AB  - Effects of ethanol in vitro on inducible nitric oxide (NO) production in RAW
      264.7 macrophages were investigated. Adding ethanol (100-600 mM) to the
      incubation medium simultaneously with lipopolysaccharide (LPS) concentration
      dependently inhibited LPS-induced NO production without being cytotoxic. This
      inhibitory effect of ethanol on NO production was almost abolished when ethanol
      was added to the medium 12 h after the start of incubation with LPS, implying
      that ethanol inhibits the induction of inducible NO synthase (iNOS). Both LPS
      induced protein and mRNA expression of iNOS were inhibited by ethanol (100-600
      mM) concentration-dependently. LPS-induced activation of signal transducer and
      activator of transcription-1 (STAT-1) was inhibited by ethanol (100-400 mM). On
      the other hand, LPS-induced translocation of nuclear factor-kappaB (NF-kappaB)
      was not affected significantly by 100-600 mM ethanol. When cells were exposed to
      ethanol for 72 h before LPS stimulation, the inhibitory effect of ethanol on
      subsequent NO production was significantly attenuated compared with that in
      control cells pretreated with vehicle for 72 h, suggesting the development of
      tolerance to the inhibitory action of ethanol. These results suggest that ethanol
      inhibits inducible NO production, probably by inhibiting STAT1 activation.
      Tolerance to this inhibitory action of ethanol is produced after chronic
      exposure.

PMID- 12237743
TI  - Inhibition of formyl-methionyl-leucyl-phenylalanine-stimulated respiratory burst
      by cirsimaritin involves inhibition of phospholipase D signaling in rat
      neutrophils.
AB  - In this study, the cellular localization of the inhibitory effect of a natural
      flavonoid cirsimaritin against formyl-methionyl-leucyl-phenylalanine (fMLP)
      induced respiratory burst in rat neutrophils was investigated. Cirsimaritin
      concentration-dependently inhibited the superoxide anion (O(*-)(2))generation and
      O(2) consumption (IC(50) 11.5+/-2.2 micro M and 17.0+/-3.9 micro M, respectively)
      of neutrophils. Cirsimaritin did not reduce, but slightly enhanced the O(*-)(2)
      generation in phorbol 12-myristate 13-acetate (PMA)-activated or arachidonic acid
      stimulated NADPH oxidase preparation as well as during the autoxidation of
      dihydroxyfumaric acid. Cirsimaritin did not elevate cellular cAMP levels, and
      only partially inhibited the fMLP-induced [Ca(2+)](i) changes in the presence or
      absence of extracellular Ca(2+). The phosphorylation of protein tyrosine,
      extracellular signal-regulated protein kinase and Akt caused by fMLP were
      attenuated by cirsimaritin in a concentration-dependent manner. In contrast,
      cirsimaritin had no effect on the phosphorylation of p38 mitogen-activated
      protein kinase. Cirsimaritin produced a concentration-dependent reduction in the
      formation of phosphatidic acid and phosphatidylethanol, in the presence of
      ethanol, from fMLP-stimulated neutrophils (IC(50) 15.1+/-6.5 micro M and 15.6+/
      3.4 micro M, respectively), but did not affect the phosphatidylethanol formation
      in response to PMA. Under the similar concentration range, cirsimaritin
      attenuated the membrane translocation of ARF and Rho A. However, the GTPgammaS
      stimulated membrane-associated ARF and Rho in cell lysate were unaffected by
      cirsimaritin. Collectively, these results indicate that the inhibition of fMLP
      induced respiratory burst by cirsimaritin in rat neutrophils is likely mainly
      through the blockade of phospholipase D signaling pathway.

PMID- 12237744
TI  - 5,7-Dihydroxytryptamine--a selective marker of dopaminergic or serotonergic
      neurons?
AB  - The aim of the present study was to investigate whether 5,7-dihydroxytryptamine
      (5,7-DHT), an autofluorescent serotonin derivative, can be used as a specific
      marker for serotonergic or dopaminergic neurons in rat mesencephalic cultures. To
      this end, primary cultures were prepared from the ventral brain stem of 14-day
      old Wistar rat foetuses and kept in culture for 10 days (DIV10). At DIV10, the
      cultures were characterized immunocytochemically with antibodies raised against
      tyrosine hydroxylase (TH; a marker for catecholaminergic/ dopaminergic neurons)
      and serotonin (5-HT). 5,7-DHT labelling of the neurons was investigated after
      incubation with 25 microM of the serotonin derivative (plus 0.005% ascorbic acid)
      for 60 min at 37 degrees C, followed by incubation with primary antibodies
      against TH or serotonin and a fluorescence (Cy3)-labelled secondary antibody.
      Using confocal laser scanning microscopy, this double immunofluorescence approach
      demonstrated that all cells which had accumulated 5,7-DHT additionally displayed
      anti-5-HT immunoreactivity, whereas no evidence was found for 5,7-DHT labelling
      of TH immunoreactive cells. Preincubation with the selective serotonin reuptake
      inhibitor fluvoxamine maleate (10 microM) prevented the loading of the 5-HT
      positive cells with 5,7-DHT. In conclusion, the present data indicate that 5,7
      DHT specifically labels serotonergic cells in rat midbrain cultures. Thus, 5,7
      DHT can be used for the identification of living serotonergic neurons even in the
      presence of dopaminergic neurons.

PMID- 12237745
TI  - On the role of monoamine oxidase-A for the maintenance of the volitional
      consumption of ethanol in two different rat models.
AB  - It is hypothesized that although the overall metabolism of ethanol in the brain
      is very limited, a very small percentage of the brain tissue may carry out that
      little amount of metabolism. Specifically, hydrogen peroxide may be used as a co
      substrate for the metabolism of ethanol to acetaldehyde by catalase and the
      action of monoamine oxidase in the monoaminergic neurons would supply the
      hydrogen peroxide. This production of acetaldehyde may result in the formation of
      novel metabolites that provide the rewarding stimulus for the consumption of
      ethanol. To test this hypothesis, a reversible inhibitor of the A-isoform of
      monoamine oxidase, BW A616U, was compared to irreversible inhibitors of one or
      both MAO-A and B isoenzymes. Doses of 12.5-75 mg/kg p.o. BW A616U reduced the
      behavioral effects, ptosis and catalepsy, due to monoamine depletion by 2.5 mg/kg
      reserpine, but these signs of monoamine depletion were evident 24 h after
      injection. In the cyanamide-induced drinking rat, 50 mg/kg BW A616U reduced
      consumption of ethanol by 37%. Phenylzine, an irreversible MAO-A and B inhibitor,
      reduced consumption of ethanol by 67%, but also food consumption; however, the
      intake of both increased during the post-treatment period. The MAO-B inhibitor,
      R(-)-deprenyl, was without effect. Both BW A616U, 50 mg/kg and 75 mg/kg, and 2.0
      mg/kg i.p. clorgyline reduced the consumption of ethanol in the genetic drinking
      Myers high-ethanol preferring (mHEP) rat and reduced the proportion of ethanol
      consumed to total fluids by over 50%. Again, R(-)-deprenyl was without effect.
      Clorgyline also markedly reduced the intake of food during the 3-day treatment
      period, only. However, the consumption of ethanol remained depressed during the 4
      days after either 75 mg/kg BW A616U or clorgyline. These data demonstrate that
      inhibition of MAO-A, but not MAO-B, reduces the volitional consumption of ethanol
      probably by preventing the formation of both biogenic aldehydes and acetaldehyde
      so that rewarding alkaloidal products cannot be formed.

PMID- 12237746
TI  - Nitric oxide is not involved in the endotoxemia-induced alterations in Ca2+ and
      ryanodine responses in mouse diaphragms.
AB  - Lipopolysaccharide (LPS, endotoxin)-induced diaphragmatic contractile dysfunction
      and sarcolemmal injury in animals has been identified. However, the precise
      nature of sepsis-related alterations in diaphragm myofiber function and the
      activity of Ca(2+) release from sarcoplasmic reticulum of skeletal muscle remain
      unclear. The present study investigated the in vivo effects of LPS on the Ca(2+)
      dependent mechanical activity and ryanodine response in mouse diaphragm and
      Ca(2+) release from isolated sarcoplasmic reticulum membrane vesicles, and aimed
      to examine the role of nitric oxide (NO) in these responses. When diaphragms were
      bathed in a solution that was Cl(-)-free, Na(+)-free, but contained high K(+), a
      Ca(2+)-induced contracture was elicited. Increases in external Ca(2+)
      concentration produced increases in peak tension of Ca(2+)-induced contracture in
      control diaphragm, while a decrease was seen in endotoxemic diaphragm. Ryanodine
      induced a marked contracture in control diaphragms, which was diminished after
      endotoxemia. This finding is correlated with the decrease of ryanodine-induced
      Ca(2+) release and the suppression of [(3)H]ryanodine binding on the isolated SR
      of the skeletal muscle from LPS-treated rats. In mice treated with LPS
      significantly increased levels of plasma nitrite and serum TNF-alpha were
      observed, changes inhibited by aminoguanidine [an inhibitor of inducible NO
      synthase (iNOS)] and pentoxifylline (an inhibitor of tumor necrosis factor-alpha
      formation), respectively. Moreover, LPS treatment resulted in a significant
      expression of mRNA for iNOS in mouse diaphragms. The inhibitory effects on Ca(2+)
      and ryanodine responses by LPS could be prevented by treatment with polymyxin B
      (LPS neutralizer) and pentoxifylline, but not by treatment with dexamethasone,
      N(G)-nitro- L-arginine or aminoguanidine (NOS inhibitors). These results imply
      that the NO-related pathway may not be involved in the dysfunction of the Ca(2+)
      release mechanism in the sarcoplasmic reticulum of mouse diaphragm during
      endotoxemia.

PMID- 12237747
TI  - Effects of neutral endopeptidase 24.11 inhibition on myocardial infarct size and
      ischemic preconditioning in rabbits.
AB  - This study was designed to determine whether inhibition of neutral endopeptidase
      24.11 (NEP) reduces infarct size and enhances protection afforded by ischemic
      preconditioning (PC) by elevation of the tissue bradykinin (BK) level in the
      heart in situ. In experiments to determine a dose of thiorphan (Thio) that
      inhibits NEP activity in the rabbit, infusion of Thio at a rate of 15 micro g/kg
      per min was found to be NEP-selective, since it increased the extent and duration
      of hypotension after BK injection (50 ng/kg and 100 ng/kg, i.v.) but did not
      inhibit pressor response to angiotensin I (100 ng/kg and 500 ng/kg, i.v.).
      Infusion of Thio at a rate of 25 micro g/kg per min blunted pressor response to
      angiotensin I by 30%, suggesting this dose partially inhibits angiotensin
      converting enzyme activity. In the second series of experiments, myocardial
      infarction was induced by 30-min coronary occlusion and 3-h reperfusion in
      rabbits. In untreated controls, infarct size as a percentage of area at risk
      (%IS/AR) was 50.1+/-4.1%, and infusion of Thio at 15 micro g/kg per min and 25
      micro g/kg per min failed to limit infarct size (54.3+/-4.0% and 50.1+/-2.8%,
      respectively). However, these doses of Thio significantly reduced %IS/AR when
      combined with PC with 2-min ischemia to 25.7+/-3.3% and 19.7+/-3.1%,
      respectively, although this submaximal PC protocol alone did not achieve
      significant cardioprotection (%IS/AR=35.6+/-4.0%). This effect of Thio on PC was
      abolished by pretreatment with icatibant (2 micro g/kg), a BK B(2) receptor
      blocker. The results of the present study suggest that NEP inhibition does not
      increase anti-infarct tolerance of the myocardium but significantly enhances
      cardioprotection of PC via a B(2) receptor-mediated mechanism.

PMID- 12237748
TI  - Activation of spinal metabotropic glutamate receptors elicits cardiovascular
      responses in pentobarbital anesthetized rats.
AB  - The aim of this study was to examine whether intrathecal (i.t.) injection of
      metabotropic glutamate (mGlu) receptor agonists at the thoracolumbar level of the
      spinal cord causes changes either in the blood pressure or in the heart rate of
      pentobarbital anesthetized rats. The broad spectrum mGlu receptor agonist (+/-)-1
      aminocyclopentane- trans-1,3-dicarboxylic acid ( trans-ACPD) and the Group III
      mGluR agonist L-(+)-2-amino-4-phosphonobutyric acid ( L-AP4) induced pressor
      effects at doses of 300 nmol and 600 nmol (i.t.) but did not induce changes at a
      lower dose (150 nmol, i.t.). The specific Group I mGlu receptor agonist ( RS)-3,5
      dihydroxyphenylglycine (3,5-DHPG), as well as the highly selective Group II mGlu
      receptor agonist 2 R,4 R-4-aminopyrrolidine-2,4-dicarboxilate (2 R,4 R-APDC),
      induced pressor effects at a dose of 300 nmol only. The compounds (150-600 nmol)
      did not modify the heart rate in these experiments. On the other hand, low doses
      of Group II mGlu receptor agonists (75 nmol 2 R,4 R-APDC; 1.5 nmol 2 S,2' R,3' R)
      2-(2',3'-dicarboxychloropropyl)glycine; DCG IV) induced hypotension and
      bradycardia when spinal N-methyl- D-aspartate (NMDA) receptors were previously
      blocked by 2-amino-5-phosphonovaleric acid (APV; 30 nmol; i.t.). The pressor
      response to trans-ACPD was probably mediated by activation of both Group I and
      Group II mGluRs because i.t. injection of either the selective Group I mGlu
      receptor antagonist ( S)-4-carboxyphenylglycine (4CPG) or the selective Group II
      mGlu receptor antagonist (2 S,3 S,4 S)-2-methyl-2-(carboxycyclopropyl)glycine
      (MCCG) antagonized the increases in the blood pressure produced by the agonist.
      Moreover, 4CPG and MCCG antagonized the pressor effects of 3,5-DHPG and 2 R,4 R
      APDC, respectively. Blockade of spinal Group II mGlu receptors by MCCG also
      prevented the hypotensive and bradycardic effects of 2 R,4 R-APDC and DCG IV in
      rats pretreated with APV. On the other hand, the pressor response to L-AP4 (300
      nmol) was prevented by the selective antagonist ( S)-2-amino-2-methyl-4
      phosphonobutanoic acid (MAP4).These results suggest that activation of spinal
      Group I, II and III mGlu receptors increases the mean blood pressure in
      pentobarbital anesthetized rats and that, after blockade of NMDA receptors, low
      doses of Group II mGlu receptor agonists induce hypotension and bradycardia.

PMID- 12237749
TI  - Electrophysiological effects of risperidone in mammalian cardiac cells.
AB  - In this study, the effects of risperidone, the widely used antipsychotic drug, on
      isolated canine ventricular myocytes and guinea-pig papillary muscles were
      analyzed using conventional microelectrode and whole cell voltage-clamp
      techniques. Risperidone concentration-dependently lengthened action potential
      duration in guinea-pig papillary muscles (EC(50)=0.29+/-0.02 micro M) and single
      canine ventricular myocytes (EC(50)=0.48+/-0.14 micro M). This effect was
      reversible, showed reverse rate dependence, and it was most prominent on the
      terminal portion of repolarization. No significant effect of risperidone on the
      resting membrane potential, action potential amplitude or maximum rate of
      depolarization was observed. In voltage-clamped canine ventricular myocytes
      risperidone caused concentration-dependent block of the rapid component of the
      delayed rectifier K(+) current ( I(Kr)), measured as outward current tails at -40
      mV, with an IC(50) of 0.92+/-0.26 micro M. Suppression of I(Kr) was not
      associated with changes in activation or deactivation kinetics. High
      concentration of risperidone (10 micro M) suppressed also the slow component of
      the delayed rectifier K(+) current ( I(Ks)) by 9.6+/-1.5% at +50 mV. These
      effects of risperidone developed rapidly and were readily reversible. Risperidone
      had no significant effect on the amplitude of other K(+) currents ( I(K1) and
      I(to)). The inhibition of cardiac I(Kr) current by risperidone may explain the
      cardiac side-effects observed occasionally with the drug. Our results suggest
      that risperidone displays class III antiarrhythmic properties, and as such, may
      produce QTc prolongation, especially in patients with long QT syndrome.
      Therefore, in psychotic patients having also cardiac disorders, ECG control may
      be suggested during risperidone therapy.

PMID- 12237750
TI  - Prolonged corticosterone treatment alters the responsiveness of 5-HT1A receptors
      to 8-OH-DPAT in rat CA1 hippocampal neurons.
AB  - Hippocampal 5-HT(1A) receptors have been shown to be suppressed by
      glucocorticoids in a variety of animal studies, however the molecular mechanism
      and the functional meaning of this effect are still not well understood. The
      present study was designed to investigate the impact of repeated administration
      of corticosterone (10 mg/kg s.c. twice daily for 7 days) on the functional
      consequences of 5-HT(1A) receptor stimulation measured electrophysiologically in
      hippocampal slices. Additionally, the effects of corticosterone on 5-HT(1A)
      receptor binding and on receptor mRNA levels in the hippocampus were studied.
      Prolonged, but not acute treatment with corticosterone attenuated (+/-)-8-hydroxy
      2-di- N-propylamino)tetralin hydrobromide (8-OH-DPAT)-induced inhibition of
      population spikes, and 8-OH-DPAT-induced hyperpolarization in rat CA1 hippocampal
      neurons. Chronic, but not acute treatment with corticosterone also decreased 5
      HT(1A) receptor binding in the CA1 region (in the ventral part only) and the
      dentate gyrus. A single dose of corticosterone increased [(3)H]8-OHDPAT binding
      in the dentate gyrus and in the CA3 and CA4 hippocampal regions. Only acute, but
      not prolonged treatment with corticosterone decreased the level of 5-HT(1A)
      receptor mRNA in the CA1 region and dentate gyrus of the hippocampus. 5-HT
      turnover in the hippocampus was not influenced by chronic corticosterone. It is
      concluded that a chronically elevated level of corticosterone can induce
      functional desensitization of 5-HT(1A) receptors in the CA1 area of the
      hippocampus, although this effect is not always followed consequently by
      decreases in 5-HT(1A) receptor synthesis in this or other areas of the
      hippocampus.

PMID- 12237751
TI  - Antagonistic effects of antimuscarinic drugs on alpha 1-adrenoceptors.
AB  - We previously observed that noradrenaline (NA)-induced contraction of the portal
      vein of rabbit was relaxed by the antimuscarinic drugs of atropine sulfate, but
      not scopolamine hydrobromide. In the present study we examined the possible
      effect of the antimuscarinic drugs of atropine sulfate, scopolamine hydrobromide,
      p-fluoro-hexa-hydro-sila-difenidol ( p-F-HHSiD, the M(3)-receptor antagonist) and
      pirenzepine (the M(1)-receptor antagonist) on alpha(1)-adrenoceptor (AR).
      Atropine and p-F-HHSiD relaxed the alpha(1)-AR agonist methoxamine-induced
      contraction of the rabbit portal vein in a concentration-dependent manner;
      however, scopolamine and pirenzepine had no such inhibitory effect. Radioligand
      binding studies with the alpha(1)-AR ligand 2-[2-(4-hydroxy-3-[(125)I]iodo
      phenyl)ethylaminomethyl]-alpha-tetralone ([(125)I]HEAT) in membrane preparations
      from mouse whole brain showed that atropine (p K(i)=5.33) and p-F-HHSiD (p
      K(i)=5.88) had higher affinities than scopolamine (p K(i)=3.17) and pirenzepine
      (p K(i)<2.70). Furthermore, atropine and p-F-HHSiD had higher affinities for all
      human cloned alpha(1)-ARs than scopolamine and pirenzepine. The results show that
      the antimuscarinic drugs atropine and p-F-HHSiD have a direct but weak
      antagonistic activity against alpha(1)-ARs.

PMID- 12237752
TI  - Evidence for a spontaneous C1840-T mutation in the RYR1 gene after DNA
      fingerprinting in a malignant hyperthermia susceptible family.
AB  - Malignant hyperthermia (MH) is a potentially lethal inherited pharmacogenetic
      syndrome due to a dysfunction of the intracellular calcium regulation of skeletal
      muscle following administration of volatile anaesthetics and depolarizing muscle
      relaxants. The ryanodine receptor of skeletal muscle (RYR1), which is an
      intracellular calcium release channel, has been proposed to be a candidate
      structure for the MH defect. In some families with a history of MH a C1840-T
      nucleotide exchange has been found in the RYR1 gene which cosegregates with the
      MH susceptible phenotype. Sixteen individuals (5 males and 11 females; age 8-68
      years, 7 MH susceptible, 9 MH non-susceptible) of a family with a history of MH
      were screened for the C1840-T mutation in the RYR1 gene using standard methods.
      DNA fingerprinting was performed in order to verify the kinship. MH
      susceptibility was determined using the standard in vitro contracture test with
      halothane and caffeine. The present article describes a German MH pedigree
      carrying a spontaneous C1840-T mutation. The mutation was detected in one
      individual of the third generation. This person was classified as MH susceptible
      according to the in vitro contracture test protocol. None of the other family
      members (6 MH susceptible and 9 MH non-susceptible persons), including the
      parents of the child carrying the mutation, presented the C to T nucleotide
      exchange at position 1840.This novel observation clearly demonstrates that only
      the detection of the C1840-T mutation may lead to the diagnosis of MH
      susceptibility, but missing the mutation does not justify diagnosing a patient as
      non-susceptible within a single pedigree.

PMID- 12237753
TI  - Stimulation of muscarinic M2 receptors inhibits atrial natriuretic peptide
      mediated relaxation in bovine tracheal smooth muscle.
AB  - The influence of muscarinic M(2) receptors to modulate the relaxant effects of
      atrial natriuretic peptide (ANP) and sodium nitroprusside (SNP) was investigated
      in bovine tracheal smooth muscle. In bovine tracheal smooth muscles contracted
      with methacholine (0.3 micro M), methoctramine (0.03 micro M), a selective
      muscarinic M(2) receptor antagonist, augmented the relaxant responses to ANP
      without affecting the responses to SNP and 8-(4-chlorophenylthio)guanosine 3',5'
      cyclic monophosphate. Pertussis toxin (PTX; 200 ng/ml for 18 h) augmented the
      relaxation and accumulation of guanosine 3',5'-cyclic monophosphate produced by
      ANP. These results suggest that the stimulation of muscarinic M(2) receptors
      suppresses ANP-induced activation of particulate guanylyl cyclase via a PTX
      sensitive G protein.

PMID- 12237754
TI  - Abstracts of the 10th World Congress of the International Society for Sexual and
      Impotence Research. Montreal, Canada, 22-26 September 2002.

PMID- 12237766
TI  - Impact of deprivation and rural residence on treatment of colorectal and lung
      cancer.
AB  - For common cancers, survival is poorer for deprived and outlying, rural patients.
      This study investigated whether there were differences in treatment of colorectal
      and lung cancer in these groups. Case notes of 1314 patients in north and
      northeast Scotland who were diagnosed with lung or colorectal cancer in 1995 or
      1996 were reviewed. On univariate analysis, the proportions of patients receiving
      surgery, chemotherapy and radiotherapy appeared similar in all socio-economic and
      rural categories. Adjusting for disease stage, age and other factors, there was
      less chemotherapy among deprived patients with lung cancer (odds ratio 0.39; 95%
      confidence intervals 0.16 to 0.96) and less radiotherapy among outlying patients
      with colorectal cancer (0.39; 0.19 to 0.82). The time between first referral and
      treatment also appeared similar in all socio-economic and rural groups. Adjusting
      for disease stage and other variables, times to lung cancer treatment remained
      similar, but colorectal cancer treatment was quicker for outlying patients
      (adjusted hazard ratio 1.30; 95% confidence intervals 1.03 to 1.64). These
      findings suggest that socio-economic status and rurality may have a minor impact
      on modalities of treatment for colorectal and lung cancer, but do not lead to
      delays between referral and treatment.

PMID- 12237767
TI  - Raltitrexed treatment promotes systemic inflammatory reaction in patients with
      colorectal carcinoma.
AB  - We studied longitudinally inflammatory reactions and serum C-reactive protein (S
      CRP) levels in 52 colorectal cancer patients treated with a median of six 3
      weekly cycles of raltitrexed 1.5-3.0 mg m(-2) combined with oral carmofur (1
      hexylcarbomoyl-5-fluorouracil) 300-400 mg m(-2) on cycle days 2-14. Thirty-nine
      (75%) of these patients had fever on days 2 to 9 after receiving raltitrexed, 49
      (94%) had fatigue Gr. > or = 1, and 49 (94%) elevated S-CRP without a documented
      infection. The systemic inflammatory composite score (consists of body
      temperature, fatigue, S-CRP, interleukin-6 (S-IL-6), S-IL-8, and tumour necrosis
      factor-alpha (S-TNF alpha) levels) was calculated in a cross-sectional one-cycle
      study involving 60 colorectal cancer patients treated with single-agent
      raltitrexed, raltitrexed and carmofur, or 5-fluorouracil-based chemotherapy (n=20
      in each group). The median S-CRP, S-IL-6, and S-TNF alpha levels were higher 7
      days after giving raltitrexed (57 vs 23 mg l(-1), 64 vs 10 ng l(-1), and 11 vs 10
      ng l(-1), respectively) or raltitrexed+carmofur (142 vs 10 mg l(-1), 64 vs 10 ng
      l(-1), and 16 vs 9 ng l(-1), respectively) than at baseline (P<0.01 for each
      comparison), but not when 5-fluorouracil-based regimens were administered. These
      findings suggest that colorectal cancer patients treated with raltitrexed may
      develop drug-related systemic inflammation, which may be difficult to
      discriminate from infection.

PMID- 12237768
TI  - A phase I trial of antibody directed enzyme prodrug therapy (ADEPT) in patients
      with advanced colorectal carcinoma or other CEA producing tumours.
AB  - Antibody-directed enzyme prodrug therapy is a targeted therapy in which a prodrug
      is activated selectively at the tumour site by an enzyme, which has been targeted
      to the tumour by an antibody (antibody-enzyme conjugate). Previous clinical
      trials have shown evidence of tumour response, however, the activated drug had a
      long half-life, which resulted in dose-limiting myelosuppression. Also, the
      targeting system, although giving high tumour to blood ratios of antibody-enzyme
      conjugate (10 000 : 1) required administration of a clearing antibody in addition
      to the antibody-enzyme conjugate. The purpose of this current study therefore was
      to attempt tumour targeting of the antibody-enzyme conjugate without the clearing
      antibody, and to investigate a new prodrug (bis-iodo phenol mustard, ZD2767P)
      whose activated form is highly potent and has a short half-life. Twenty-seven
      patients were treated with antibody-directed enzyme prodrug therapy using A5CP
      antibody-enzyme conjugate and ZD2767P prodrug, in a dose-escalating phase I
      trial. The maximum tolerated dose of ZD2767P was reached at 15.5 mg m(-2)x three
      administrations with a serum carboxypeptidase G2 level of 0.05 U ml(-1).
      Myelosuppression limited dose escalation. Other toxicities were mild. Patients'
      quality of life was not adversely affected during the trial as assessed by the
      measures used. There were no clinical or radiological responses seen in the
      study, but three patients had stable disease at day 56. Human anti-mouse antibody
      and human anti-carboxypeptidase G2 antibody were produced in response to the
      antibody enzyme conjugate (A5CP). The antibody-enzyme conjugate localisation data
      (carboxypeptidase G2 enzyme levels by HPLC on tumour and normal tissue samples,
      and gamma camera analysis of I-131 radiolabelled conjugate) are consistent with
      inadequate tumour localisation (median tumour: normal tissue ratios of antibody
      enzyme conjugate of less than 1). A clearance system is therefore desirable with
      this antibody-enzyme conjugate or a more efficient targeting system is required.
      ZD2767P was shown to clear rapidly from the circulation and activated drug was
      not measurable in the blood. ZD2767P has potential for use in future antibody
      directed enzyme prodrug therapy systems.

PMID- 12237769
TI  - A phase I and pharmacokinetic study of MAG-CPT, a water-soluble polymer conjugate
      of camptothecin.
AB  - Polymeric drug conjugates are a new and experimental class of drug delivery
      systems with pharmacokinetic promises. The antineoplastic drug camptothecin was
      linked to a water-soluble polymeric backbone (MAG-CPT) and administrated as a 30
      min infusion over 3 consecutive days every 4 weeks to patients with malignant
      solid tumours. The objectives of our study were to determine the maximal
      tolerated dose, the dose-limiting toxicities, and the plasma and urine
      pharmacokinetics of MAG-CPT, and to document anti-tumour activity. The starting
      dose was 17 mg m(-2) day(-1). Sixteen patients received 39 courses at seven dose
      levels. Maximal tolerated dose was at 68 mg m(-2) day(-1) and dose-limiting
      toxicities consisted of cumulative bladder toxicity. MAG-CPT and free
      camptothecin were accumulated during days 1-3 and considerable amounts of MAG-CPT
      could still be retrieved in plasma and urine after 4-5 weeks. The half-lives of
      bound and free camptothecin were equal indicating that the kinetics of free
      camptothecin were release rate dependent. In summary, the pharmacokinetics of
      camptothecin were dramatically changed, showing controlled prolonged exposure of
      camptothecin. Haematological toxicity was relatively mild, but serious bladder
      toxicity was encountered which is typical for camptothecin and was found dose
      limiting.

PMID- 12237770
TI  - Effects of patient selection on the applicability of results from a randomised
      clinical trial (EORTC 10853) investigating breast-conserving therapy for DCIS.
AB  - Selection of patients for randomised clinical trials may have a large impact on
      the applicability of the study results to the general population presenting the
      same disorder. However, clinical characteristics and outcome data on non-entered
      patients are usually not available. The effects of patient selection for the
      EORTC 10853 trial investigating the role of radiotherapy in breast conserving
      therapy for ductal carcinoma in situ have been studied, in an analysis of all
      patients treated for ductal carcinoma in situ in five participating institutes.
      The reasons for not entering patients were evaluated and treatment results of the
      randomised patients were compared to those not entered. A total of 910 patients
      were treated for ductal carcinoma in situ. Of these, 477 (52%) were ineligible,
      with the size of the lesion being the main reason for ineligibility (30% of all
      ductal carcinoma in situ). Of the 433 eligible patients, 278 (64%) were
      randomised into the trial. The main reasons for non-entry of eligible patients
      were either physicians' preference for one of the treatment arms (26%) or
      patients' refusal (9%). These percentages showed significant variation among the
      institutes. At 4 years follow-up, those patients not entered in the trial and
      treated with local excision and radiotherapy, had higher local recurrence rates
      than the patients randomised in the trial and treated with the same approach, (17
      vs 2%, P=0.03). The patients treated with local excision alone had equal local
      recurrence rates (11% in both groups). Selection of patients may explain the
      differences in outcome of the randomised patients, and those not-entered. Thus,
      the results of this trial may not be applicable to all patients with ductal
      carcinoma in situ.

PMID- 12237771
TI  - Increased aquaporin 1 water channel expression in human brain tumours.
AB  - Aquaporin 1 is a water channel protein. There was little aquaporin 1
      immunoreactivity in normal brain parenchyma. In astrocytomas, aquaporin 1 was
      expressed in microvessel endothelia and neoplastic astrocytes. In metastatic
      carcinomas, aquaporin 1 was present in microvessel endothelia and reactive
      astrocytes. Aquaporin 1 may participate in the formation of brain tumour oedema.

PMID- 12237772
TI  - DNA topoisomerase I and II expression in drug resistant germ cell tumours.
AB  - A small number of testicular germ cell tumours are refractory to current
      chemotherapy regimens. DNA topoisomerase I is the target for several new drugs
      and a potential candidate treatment for chemorefractory germ cell tumours. DNA
      topoisomerase II alpha is the target for etoposide, which is currently used
      regularly in germ cell tumour treatment. The expression of DNA topoisomerase I
      and II alpha were therefore assessed immunohistochemically in a range of
      testicular tumours, especially those with persistent malignant elements on
      retroperitoneal lymph node dissection. Pre-chemotherapy orchidectomy specimens
      were matched with post-chemotherapy retroperitoneal lymph node dissections to
      examine changes in expression. There was considerable variation in the expression
      of topoisomerase I in different tumour types. Both yolk sac tumours and teratoma,
      mature showed universal expression of topoisomerase I, while 38% of seminomas and
      30% of embryonal carcinomas were positive. Strong topoisomerase II alpha
      expression was found in embryonal carcinoma. There was a negative correlation
      between topoisomerase I and II alpha expression (P=0.004) and downregulation of
      topoisomerase II alpha after chemotherapy (P=0.02). Topoisomerase I expression
      appears to increase in those cases with residual teratoma, mature, but is largely
      unchanged in those cases remaining as embryonal carcinoma. These results suggest
      that topoisomerase I inhibitors may be useful in chemorefractory germ cell
      tumours, especially yolk sac tumours and where there are unresectable residual
      teratoma, mature deposits.

PMID- 12237773
TI  - SMAD4 is a predictive marker for 5-fluorouracil-based chemotherapy in patients
      with colorectal cancer.
AB  - The gene for the transducer of transforming growth factor-beta/bone morphogenetic
      protein signalling SMAD4, a potential suppressor of colorectal carcinogenesis, is
      located at the chromosomal region 18q21. In order to evaluate the clinical
      relevance of SMAD4 deletion, gene copy alterations were determined by copy dosage
      using real-time quantitative PCR in 202 colorectal tumour biopsies from a
      previous randomised study of adjuvant chemotherapy. Patients with normal SMAD4
      diploidy turned out to have a three-fold higher benefit of 5-fluorouracil-based
      adjuvant chemotherapy with a border line significance (overall survival: 3.23,
      P=0.056; disease-free survival: 2.89, P=0.045). These data are consistent with
      the previous observation that patients whose cancer had retention of the 18q21
      region had a significantly higher benefit from 5-fluorouracil-based therapy.
      Moreover, these results may provide a refinement at the gene level of the
      clinical relevance of 18q21 deletion, thereby suggesting SMAD4 as a predictive
      marker in colorectal cancer. This data also indicate that integrity of this
      component of the transforming growth factor-beta/bone morphogenetic protein
      signalling pathway may be a critical factor for benefit of chemotherapy in
      patients with colorectal cancer.

PMID- 12237774
TI  - Rho GTPases in human breast tumours: expression and mutation analyses and
      correlation with clinical parameters.
AB  - In the present study, we addressed the question of a putative relevance of Rho
      proteins in tumour progression by analysing their expression on protein and mRNA
      level in breast tumours. We show that the level of RhoA, RhoB, Rac1 and Cdc42
      protein is largely enhanced in all tumour samples analysed (n=15) as compared to
      normal tissues originating from the same individual. The same is true for (32)P
      ADP-ribosylation of Rho proteins which is catalysed by Clostridium botulinum
      exoenzyme C3. Also the amount of Rho-GDI and ERK2 as well as the level of overall
      (32)P-GTP binding activity was tumour-specific elevated, yet to a lower extent
      than Rho proteins. Although the amount of Rho proteins was enhanced in tumours,
      most of them did not show changes in rho mRNA expression as compared to the
      corresponding normal tissue. Thus, elevated gene expression seems not to be the
      underlying mechanism of tumour-specific overexpression of Rho proteins. Sequence
      analysis of RhoA, RhoB, RhoC and Rac1 failed to detect any mutations in both the
      GTP-binding site and effector binding region. By analysing >50 tumour samples,
      the amount of RhoA-like proteins (i.e. RhoA, B, C), but not of Rac1, was found to
      significantly increase with histological grade and proliferation index. Rho
      protein expression was neither related to p53 nor to HER-2/neu oncogene status.
      Expression of rho mRNAs did not show a significant increase with histological
      grade. Overall the data show that (1) Rho proteins are overexpressed in breast
      tumours (2) overexpression is not regulated on the mRNA level (3) the expression
      level of RhoA-like proteins correlates with malignancy and (4) Rho proteins are
      not altered by mutation in breast tumours.

PMID- 12237775
TI  - Biological activity of the thyroid TRK-T3 oncogene requires signalling through
      Shc.
AB  - The thyroid TRK-T3 oncogene, produced by a chromosomal translocation, is a
      chimeric, constitutively activated version of the NTRK1/NGF receptor and it is
      able to transform NIH3T3 cells and differentiate PC12 cells. TRK-T3 oncoprotein
      triggers multiple signal transduction pathways. Among others, TRK-T3 binds and
      phosphorylates the Shc and SNT1/FRS2 adaptor proteins both involved in coupling
      the receptor tyrosine kinase to the mitogen-activated protein kinase pathway by
      recruiting Grb2/SOS. We were interested in defining the role of Shc in the
      oncogenesis by TRK-T3. The mutation of TRK-T3 tyrosine 291, docking site for both
      Shc and FRS2, abrogates the oncogene biological activity. To directly explore the
      role of Shc we used the ShcY317F mutant, which carries the mutation of a tyrosine
      residue involved in Grb2 recruitment. We demonstrated that the ShcY317F mutant
      exerts an inhibitory effect on TRK-T3 transforming activity. Such effect can be
      modulated by the amount of ShcY317F protein and affects the viability of cells
      expressing TRK-T3 by means of a mechanism involving apoptosis. Our results
      indicate a definitive role of the adaptor protein Shc in TRK-T3 transforming
      activity.

PMID- 12237776
TI  - Genetic aberrations of c-myc and CCND1 in the development of invasive bladder
      cancer.
AB  - Detrusor muscle invasive transitional cell carcinoma is associated with poor
      prognosis and is responsible for the majority of bladder cancer related deaths.
      Amplifications of c-myc and CCND1 are associated with detrusor-muscle-invasive
      transitional cell carcinoma, however, their precise role in driving disease
      progression is unclear. Fluorescence in situ hybridisation on archival tissue
      from 16 patients with primary diagnosis of > or = pT2 transitional cell carcinoma
      and 15 cases with primary pTa/pT1 disease subsequently progressing to detrusor
      muscle-invasion was performed, in the latter group both pre and post muscle
      invasive events were studied. No patients presenting with >/=pT2 had
      amplification of c-myc, two out of 16 (12.5%) had CCND1 amplification. Of
      patients who developed > or = pT2, two out of 15 (13.3%) had amplification of c
      myc, both in > or = pT2, five out of 15 (33.3%) had CCND1 amplification, two in
      pTa/pT1 tumours, three in > or = pT2 transitional cell carcinomas. In total, two
      out of 31 (6.5%) of patients' > or = pT2 TCCs were amplified for c-myc and six
      out of 31 (19%) were amplified for CCND1. Eighty-seven per cent (40 out of 46) of
      tumours were polysomic for chromosome 8 and 80% (37 out of 46) were polysomic for
      chromosome 11 and this reflected the high copy numbers of c-myc and CCND1
      observed. In almost all cases an increase in c-myc/CCND1 copy number occurred
      prior to invasion and persisted in advanced disease. Amplification of CCND1 or
      alterations in c-myc/CCND1 early in bladder cancer may have clinical relevance in
      promoting and predicting progression to detrusor-muscle-invasive transitional
      cell carcinoma.

PMID- 12237777
TI  - Secreted and tumour targeted human carboxylesterase for activation of irinotecan.
AB  - Irinotecan (CPT-11) is an anticancer agent for the treatment of colon cancer. CPT
      11 can be considered as a prodrug, since it needs to be activated into the toxic
      drug SN-38 by the enzyme carboxylesterase. An approach to achieve tumour specific
      activation of CPT-11 is to transduce the cDNA encoding carboxylesterase into
      tumour cells. A secreted form of carboxylesterase may diffuse through a tumour
      mass and may activate CPT-11 extracellularly. This could enhance the antitumour
      efficacy by exerting a bystander effect on untransduced cells. In addition a
      secreted tumour-targeted form of carboxylesterase should prevent leakage of the
      enzyme from the site of the tumour into the circulation. We have constructed a
      secreted form of human liver carboxylesterase-2 by deletion of the cellular
      retention signal and by cloning the cDNA downstream of an Ig kappa leader
      sequence. The protein was secreted by transfected cells and showed both enzyme
      activity and efficient CPT-11 activation. To obtain a secreted, tumour-targeted
      form of carboxylesterase-2 the cDNA encoding the human scFv antibody C28 directed
      against the epithelial cell adhesion molecule EpCAM, was inserted between the
      leader sequence and carboxylesterase-2. This fusion protein showed CPT-11
      activation and specific binding to EpCAM expressing cells. Importantly, in
      combination with CPT-11 both recombinant carboxylesterase proteins exerted strong
      antiproliferative effects on human colon cancer cells. They are, therefore,
      promising new tools for gene directed enzyme prodrug therapy approaches for the
      treatment of colon carcinoma with CPT-11.

PMID- 12237778
TI  - Induction of breast cancer resistance protein by the camptothecin derivative DX
      8951f is associated with minor reduction of antitumour activity.
AB  - DX-8951f (exatecan mesylate), a new water-soluble derivative of camptothecin, is
      currently being evaluated in phase II clinical trials. Resistance may be acquired
      when treating cancer patients with DX-8951f. Therefore, we selected a subline of
      the human ovarian cancer cell line A2780 for resistance against DX-8951f to
      investigate possible mechanisms of resistance. This DX-8951f-resistant subline,
      designated 2780DX8 (resistance factor=9.3), displayed a typical cross-resistance
      pattern including compounds, such as topotecan (resistance factor =34), SN-38
      (resistance factor =47), mitoxantrone (resistance factor =59) and doxorubicin
      (resistance factor =2.9), which have previously been associated with the
      expression of breast cancer resistance protein. 2780DX8 cells did not show
      changes in the topoisomerase I gene, in topoisomerase I protein levels or
      catalytic activity. Overexpression of breast cancer resistance protein could be
      detected, both at the mRNA and protein level, while staining for Pgp, MRP1, or
      LRP was negative. GF120918, an inhibitor of breast cancer resistance protein, was
      able to reverse the DX-8951f-induced resistance in 2780DX8 cells. In vivo
      experiments in well-established 2780DX8 human tumour xenografts demonstrated that
      the growth inhibition induced by CPT-11 was more affected by breast cancer
      resistance protein expression than that of DX-8951f. These data indicate for the
      first time that DX-8951f is able to induce breast cancer resistance protein as a
      mechanism of resistance. Breast cancer resistance protein, however, results in
      only minor reduction of antitumour activity of DX-8951f which is an advantage
      over topotecan and CPT-11/SN-38.

PMID- 12237779
TI  - Dimethylarginine dimethylaminohydrolase I enhances tumour growth and
      angiogenesis.
AB  - Angiogenesis is a prerequisite for tumour progression and is highly regulated by
      growth factors and cytokines a number of which also stimulate the production of
      nitric oxide. Asymmetric dimethylarginine is an endogenous inhibitor of nitric
      oxide synthesis. Asymmetric dimethylarginine is metabolised by dimethylarginine
      dimethylaminohydrolase. To study the effect of dimethylarginine
      dimethylaminohydrolase on tumour growth and vascular development, the rat C6
      glioma cell line was manipulated to overexpress the rat gene for dimethylarginine
      dimethylaminohydrolase I. Enhanced expression of dimethylarginine
      dimethylaminohydrolase I increased nitric oxide synthesis (as indicated by a two
      fold increase in the production of cGMP), expression and secretion of vascular
      endothelial cell growth factor, and induced angiogenesis in vitro. Tumours
      derived from these cells grew more rapidly in vivo than cells with normal
      dimethylarginine dimethylaminohydrolase I expression. Immunohistochemical and
      magnetic resonance imaging measurements were consistent with increased tumour
      vascular development. Furthermore, dimethylarginine dimethylaminohydrolase
      activity was detected in a series of human tumours. This data demonstrates that
      dimethylarginine dimethylaminohydrolase plays a pivotal role in tumour growth and
      the development of the tumour vasculature by regulating the concentration of
      nitric oxide and altering vascular endothelial cell growth factor production.

PMID- 12237784
TI  - Synthesis of research findings regarding assessment/diagnosis of Alzheimer's
      disease--Part I.
AB  - Alzheimer's disease (AD) is predicted to strike 14 million Americans by 2050. To
      date, the only accurate way to diagnose this devastating disease is at autopsy,
      so the importance of ruling out other diseases and instituting a plan of care for
      early symptoms is vital. The purpose of this review is to synthesize the
      knowledge about the assessment and diagnosis of Alzheimer's disease so clinicians
      can understand what is needed to differentiate AD from other diseases/conditions.

PMID- 12237781
TI  - Oestrogen receptor beta: how should we measure this?

PMID- 12237780
TI  - Expression of paclitaxel-inactivating CYP3A activity in human colorectal cancer:
      implications for drug therapy.
AB  - Cytochrome P450 3A is a drug-metabolising enzyme activity due to CYP3A4 and
      CYP3A5 gene products, that is involved in the inactivation of anticancer drugs.
      This study analyses the potential of cytochrome P450 3A enzyme in human
      colorectal cancer to impact anticancer therapy with drugs that are cytochrome
      P450 3A substrates. Enzyme activity, variability and properties, and the ability
      to inactivate paclitaxel (taxol) were analysed in human colorectal cancer and
      healthy colorectal epithelium. Cytochrome P450 3A enzyme activity is present in
      healthy and tumoral samples, with a nearly 10-fold interindividual variability.
      Nifedipine oxidation activity+/-s.d. for colorectal cancer microsomes was 67.8+/
      36.6 pmol min(-1) mg(-1). The K(m) of the tumoral enzyme (42+/-8 microM) is
      similar to that in healthy colorectal epithelium (36+/-8 microM) and the human
      liver enzyme. Colorectal cancer microsomes metabolised the anticancer drug
      paclitaxel with a mean activity was 3.1+/-1.2 pmol min(-1) mg(-1). The main
      metabolic pathway is carried out by cytochrome P450 3A, and it is inhibited by
      the cytochrome P450 3A-specific inhibitor ketoconazole with a K(I) value of 31
      nM. This study demonstrates the occurrence of cytochrome P450 3A-dependent
      metabolism in colorectal cancer tissue. The metabolic activity confers to cancer
      cells the ability to inactivate cytochrome P450 3A substrates and may modulate
      tumour sensitivity to anticancer drugs.

PMID- 12237785
TI  - Synthesis of research findings regarding the care of people with Alzheimer's
      disease--Part II.
AB  - The purpose of this review is to present knowledge about the treatment of
      Alzheimer's disease (AD). Synthesized research findings about the pharmacological
      and nonpharmacological interventions used with patients who have Alzheimer's
      disease are presented and are followed by a discussion regarding the actions
      nurses can initiate to enhance functioning and delay institutionalization. While
      there is a great deal of interest and study of AD treatment, the research is
      variable and often with small populations. Even so, the results of these studies
      are promising, as they provide information about the ways AD symptoms can be
      controlled by medication and other means.

PMID- 12237786
TI  - Detoxification of opiate addicts with multiple drug abuse: a comparison of
      buprenorphine vs. methadone.
AB  - Over the last few years, there has been a growing tendency for opioid addicts to
      abuse multiple drugs, although many patients are in substitution therapy with
      methadone. Abuse of multiple drugs leads to a more complicated withdrawal
      syndrome; it is therefore necessary to investigate new drug strategies as a
      treatment for detoxification. Buprenorphine appears to be an effective and safe
      drug in opioid-addicted patient detoxification. In this study, we have compared
      the short-term efficacy of an 11-day low-dose buprenorphine/14-day carbamazepine
      regime [BPN/CBZ] (n = 14) to an 11-day methadone/14-day carbamazepine regime
      [MET/CBZ] (n = 12) in a double-dummy, randomized 14-day inpatient detoxification
      treatment study. Twenty-six inpatients met the DSM-IV criteria for opioid
      dependence and were included in this study. All patients abused various
      additional drugs. Fourteen of 26 patients (53.8 %) completed the study. Seven non
      completers (seven of 12 = 58.3 %) were treated with methadone/carbamazepine and
      five non-completers (five of 14 = 35.7 %) received buprenorphine/carbamazepine,
      but the difference in the dropout rate was not significant. However, patients
      with buprenorphine/carbamazepine showed significantly fewer withdrawal symptoms
      after the first two weeks of treatment. The present study supports the hypothesis
      that buprenorphine/carbamazepine is more effective than methadone/carbamazepine
      in detoxification strategies for opioid addict with additional multiple drug
      abuse. No severe side effects occurred during treatment in either group.

PMID- 12237787
TI  - Trimipramine in primary insomnia: results of a polysomnographic double-blind
      controlled study.
AB  - In recent years, sedating antidepressants have been increasingly used to treat
      primary insomnia. Up to now, only one open pilot study with trimipramine and one
      double-blind placebo-controlled study with doxepin have provided scientific
      support for this approach in treating primary insomnia. In order to test the
      hypothesis that sedating antidepressants are useful in the treatment of primary
      insomnia, the effect of trimipramine on objectively and subjectively measured
      parameters of sleep was investigated in a double-blind placebo- and lormetazepam
      controlled study in a sample of 55 patients with primary insomnia attending
      outpatient sleep-disorder clinics. Trimipramine was selected since it has shown
      positive effects on sleep continuity with a lack of REM sleep suppression in
      studies on depressed patients and in one pilot study on patients with primary
      insomnia. Trimipramine at an average dose of 100 mg over a period of 4 weeks
      significantly enhanced sleep efficiency, but not total sleep time (which had been
      the primary target variable) compared to placebo as measured by polysomnography.
      Changes in objective sleep parameters were paralleled by changes in subjective
      sleep parameters. Trimipramine did not suppress REM sleep. Lormetazepam decreased
      wake time and sleep stage 3 and increased REM sleep compared to placebo. After
      switching trimipramine to placebo, sleep parameters returned to baseline. There
      was no evidence of any rebound effect from trimipramine. Side effects from
      trimipramine were only marginal. This first double-blind placebo-controlled study
      with trimipramine suggests its efficacy in the treatment of primary insomnia.
      However, due to the large intra- and interindividual variance in the parameters
      of interest before and during treatment a larger sample size would have been
      necessary to strengthen the validity of our findings.

PMID- 12237788
TI  - Plasma levels of catecholamine metabolites predict the response to sulpiride or
      fluvoxamine in major depression.
AB  - We investigated the relationships between the changes in plasma catecholamine
      metabolites obtained from depressed patients before and after administration of
      sulpiride, a benzamide compound, or fluvoxamine, a selective serotonin reuptake
      inhibitor (SSRI), and between clinical responses to treatment with each of these
      drugs. Responders to sulpiride had significantly lower plasma homovanillic acid
      (pHVA) levels before administration of sulpiride than did non-responders or
      controls (responders: 4.5 +/- 3.1 ng/ml, non-responders: 11.1 +/- 5.9 ng/ml,
      controls: 10.9 +/- 5.3 ng/ml). Positive relationships were observed between
      changes in pHVA levels and improvement rates in the 17-item Hamilton Depression
      Rating Scale (Ham-D). In contrast, responders to fluvoxamine had significantly
      higher plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels before
      administration of fluvoxamine than did non-responders or controls (responders:
      8.5 +/- 1.8 ng/ml, non-responders: 5.9 +/- 2.I ng/ml, controls: 5.2 +/- 2.9
      ng/ml). Negative relationships were observed between changes in pMHPG levels and
      improvement rates in Ham-D. These results suggest that lower pretreatment pHVA
      levels and higher pretreatment levels of pMHPG might be predictors of response to
      sulpiride and fluvoxamine, respectively, and that sulpiride might produce a
      functional increase in the dopaminergic system, resulting in improvement in some
      depressive symptoms; fluvoxamine, on the other hand, might produce a functional
      decrease in the noradrenergic system via serotonergic neurons, resulting in
      improvement of those symptoms.

PMID- 12237789
TI  - The trigonometric responder approach: a new method for detecting responders to
      pharmacological or experimental challenges.
AB  - The paper presents a newly developed response measure that is particularly
      suitable for the evaluation of pharmacokinetic data. This method is based on
      trigonometric considerations, defining a hormone response as the difference
      between the angle of the slope of the curve before and after drug intake. In
      addition, the size of this difference is compared to the difference obtained in
      placebo conditions. In this way, the trigonometric response measure overcomes one
      of the most problematic shortcomings of the 'area under the curve' (AUC)
      approach, the problem of the initial value. We will present the mathematical
      background of the trigonometric method and demonstrate its usefulness by
      evaluating empirical data (a pharmacological challenge test using the dopamine
      agonist lisuride) and comparing it to classical AUC measures. This has been
      achieved by contrasting both approaches with responder definitions according to
      binary time series analysis and the peak value of the curve.

PMID- 12237790
TI  - Clozapine in patients with chronic schizophrenia: serum level, EEG and memory
      performance.
AB  - The atypical antipsychotic clozapine causes EEG alterations, and may lead to
      memory impairments due to its anticholinergic properties. The relationships
      between clozapine serum level, quantitative EEG parameters and performance in
      vigilance and memory tasks were studied in a group of 17 chronically ill
      schizophrenic patients under maintenance treatment with clozapine at stable
      dosages. There were negative correlations between clozapine serum levels and the
      amount of high-frequency EEG activity and positive correlations between high
      frequency EEG activity and memory performance. These findings may suggest that
      clozapine treatment brings about dose-dependent impairments of vigilance and
      memory, for which a reduction of high-frequency EEG activity is indicative.

PMID- 12237791
TI  - Norepinephrine transporter polymorphism and personality trait of reward
      dependence in male alcoholics.

PMID- 12237792
TI  - Charcoal enhancement of treatment for tricyclic-induced mania.
AB  - Induction of mania by tricyclic antidepressants (TCAs) is controversial, with
      indirect evidence for and against it. Unusual direct evidence of it was observed
      in a 77-year-old female patient having ingested an amitriptyline overdose. Mania
      developed while the TCA blood levels were high, and responded to a combination of
      charcoal and valproate. However, mania reappeared when charcoal was discontinued,
      and disappeared again when it was restarted. This time course suggests a
      therapeutic advantage for adding charcoal to valproate in treating tricyclic
      induced mania. Presumably, charcoal might have removed a mania-inducing
      metabolite of amitriptyline. Moreover, repeated doses of oral activated charcoal
      accelerated the elimination of TCA from the blood stream to several times its
      original rate, which is consistent with interruption of the enterohepatic
      circulation. This enhanced elimination and improved outcome illustrate the value
      of repeated charcoal doses after TCA overdose, and suggest its use when mania
      develops in a patient who takes an antidepressant, at least amitriptyline or
      nortriptyline.

PMID- 12237793
TI  - Mefloquine-induced paranoid psychosis and subsequent major depression in a 25
      year-old student.

PMID- 12237795
TI  - Pressure generated on a simulated oral analog by impression materials in custom
      trays of different designs.
AB  - PURPOSE: To measure the pressure exerted by maxillary edentulous impressions
      composed of 3 commonly used impression materials using four different impression
      tray configurations. MATERIALS AND METHODS: The study was performed using an oral
      analog that simulated an edentulous maxillary arch. Three pressure transducers
      were imbedded in the oral analog, 1 in the mid-palate area and the other 2 in the
      right and left ridge (maxillary first premolar areas). Custom trays of 4
      different configurations were fabricated. The 3 impression materials tested were
      irreversible hydrocolloid, light-body and medium-body vinyl polysiloxane, and
      polysulfide. A total of 128 impressions were made. The custom tray and the oral
      analog were mounted using a reline jig. A Satec universal testing machine was
      used to apply a constant pressure of 2 kg/cm(2) over a period of 5 minutes on the
      loaded custom tray. The pressure was recorded every 10 seconds. Factorial
      analysis of variance and Tukey's multiple comparison test were used to analyze
      the results. RESULTS: A significant difference in the pressure produced using
      different impression materials was found (p < or =0.001). Irreversible
      hydrocolloid and medium-body vinyl polysiloxane produced a significantly higher
      pressure than light-body vinyl polysiloxane and polysulfide impression materials.
      The presence of holes and/or relief did not significantly alter the magnitude of
      pressure. CONCLUSION: All impression materials produced pressure during maxillary
      edentulous impression making. Tray modification was not important in changing the
      amount of pressure produced. The impression materials used had more effect on the
      pressure produced during impression making on the simulated oral analog.

PMID- 12237796
TI  - The effect of disinfectants on the properties of dental gypsum: 1. Mechanical
      properties.
AB  - PURPOSE: This study was conducted to evaluate the effect of selected
      disinfectants incorporated in the liquid of dental stones on material strength
      properties with the aim of developing a material with acceptable mechanical
      properties. MATERIALS AND METHODS: Two types of dental stone (types III and V)
      were mixed with aqueous solutions of 0.525% sodium hypochlorite, 0.1% and 10%
      povidone-iodine, and 2% glutaraldehyde, and with water as a control. The
      liquid/powder ratios recommended by the manufacturer were used. These materials
      were subjected to further modification by adding a mixture of 1.0% gum arabic and
      0.132% calcium hydroxide to the hemihydrate powders before mixing with the
      disinfectant solutions at 2 different liquid/powder ratios for each. Both the
      regular and the modified materials were tested for compressive and diametral
      tensile strength after 1 hour and 1 week from the start of the mix. The structure
      of set materials was determined by scanning electron microscopy examination of
      fracture surfaces. RESULTS: The disinfectants often reduced the strength of both
      types of dental stone. However, using either 0.1% povidone-iodine or 0.525%
      sodium hypochlorite resulted in strength values comparable with that of the
      control. The addition of gum arabic and calcium hydroxide helped reduce the
      mixing liquid/powder ratios, improving the strength properties of the disinfected
      materials. CONCLUSIONS: Chemical disinfectants reduce the strength of dental
      gypsum when used as mixing water substitutes. Gum arabic and calcium hydroxide
      additives permit a lower liquid/powder ratio and can help offset this weakening.

PMID- 12237798
TI  - Rehabilitation of a bulimic patient using endosteal implants.
AB  - This article describes the dental rehabilitation of a bulimic patient using
      endosteal implants. Although the patient, a 31-year-old woman with a long history
      of bulimia nervosa, had been receiving medical and psychological treatment, the
      condition was not completely controlled. Clinical examination revealed multiple
      crowns with extensive cervical caries. The prognosis for all remaining teeth was
      poor. After extractions, implant therapy was implemented to provide support for
      fixed prostheses. After the implants were uncovered and during provisional
      therapy, the peri-implant tissue exhibited inflammation and lack of keratinized
      tissue requiring additional periodontal procedures before definitive restorations
      could be placed. Because of the difficulty in managing the peri-implant tissue
      during the many phases of implant therapy, treatment was challenging. One year
      after treatment, the patient's low self-esteem had improved substantially and her
      restorations provided satisfactory esthetics and function.

PMID- 12237797
TI  - Retention strengths of five luting cements on prefabricated dowels after root
      canal obturation with a zinc oxide/eugenol sealer: 1. Dowel space
      preparation/cementation at one week after obturation.
AB  - PURPOSE: This investigation examined the effect of 5 different cements on the
      retention strength of prefabricated endodontic dowels placed into root canals
      previously obturated with gutta percha and a zinc oxide/eugenol (ZOE) sealer.
      MATERIALS AND METHODS: Ninety-six single-rooted teeth were decoronated, filed,
      cleaned, sequentially shaped, and divided into 6 groups of 16 specimens each.
      Five of the groups were then obturated with gutta percha and a ZOE sealer. One
      group was not obturated and served as the control group. Dowel space preparation
      and dowel cementation for all groups were completed 1 week later. Ten-mm deep
      dowel spaces were prepared using size 6 Gates Glidden drills. Size 5 Paraposts
      were then cemented with 5 different cements: Panavia 21 for group 1 (unobturated
      controls) and group 2; Ketac-Cem glass ionomer for group 3; Fleck's zinc
      phosphate for group 4; Parapost (composite) Cement for group 5; and C&B Metabond
      4-META for group 6. After 48 hours, the dowels were removed using a universal
      testing machine in tensile mode at 1 mm min(-1). RESULTS: The following results
      were found (all values in kg): group 1 (controls; Panavia 21) mean = 61.81, 95%
      CI = +/-8.65; group 2 (Panavia 21), mean=43.15, 95% CI = +/-7.81; group 3 (Ketac
      Cem), mean =34.45, 95% CI = +/-4.93; group 4 (zinc phosphate), mean = 25.07, 95%
      CI = +/-5.03; group 5 (Parapost Cement), mean = 24.99, 95% CI = +/-5.35. None of
      the group 6 (C&B Metabond) specimens developed measurable bond strengths, so this
      group was excluded from parametric statistical analyses. An analysis of variance
      (ANOVA) showed a significant effect of group; pairwise multiple comparison
      procedures (Tukey test) showed that group 1 (controls) had significantly greater
      retention than all other groups (p <0.001); group 2 (Panavia 21) had
      significantly greater retention than groups 4 (zinc phosphate) and 5 (Parapost
      cement) (p <0.001). None of the other pairwise comparisons were statistically
      different. CONCLUSION: Paraposts cemented with Panavia 21 in unobturated root
      canals exhibited significantly higher retention than Paraposts luted with Panavia
      21 and 4 different cements into dowel spaces prepared 1 week after obturation
      with gutta percha/ZOE sealer (p <0.001). Among the obturated groups, Panavia 21
      cement (group 2) demonstrated significantly greater retention of Paraposts than
      zinc phosphate (group 4) and Parapost composite (group 5) cements (p <0.001).
      Ketac-Cem glass ionomer cement (group 3) had intermediate retention values that
      were not statistically different than those of groups 2, 4, and 5 (p >0.05). The
      4-META cement, C&B Metabond, failed to polymerize.

PMID- 12237799
TI  - Classification system for partial edentulism.
AB  - The American College of Prosthodontists (ACP) has developed a classification
      system for partial edentulism based on diagnostic findings. This classification
      system is similar to the classification system for complete edentulism previously
      developed by the ACP. These guidelines are intended to help practitioners
      determine appropriate treatments for their patients. Four categories of partial
      edentulism are defined, Class I to Class IV, with Class I representing an
      uncomplicated clinical situation and class IV representing a complex clinical
      situation. Each class is differentiated by specific diagnostic criteria. This
      system is designed for use by dental professionals involved in the diagnosis and
      treatment of partially edentulous patients. Potential benefits of the system
      include (1) improved intraoperator consistency, (2) improved professional
      communication, (3) insurance reimbursement commensurate with complexity of care,
      (4) improved screening tool for dental school admission clinics, (5) standardized
      criteria for outcomes assessment and research, (6) enhanced diagnostic
      consistency, and (7) simplified aid in the decision to refer a patient.

PMID- 12237800
TI  - Survey of implant experience by prosthodontists in the United States.
AB  - PURPOSE: The paper presents results of a survey of members of the American
      College of Prosthodontists (ACP) conducted to determine experiences and practices
      with dental implants. MATERIALS AND METHODS: Preliminary survey questions
      regarding the prosthetic and surgical use of dental implants were developed. The
      master list of questions was distributed to communities of interest to establish
      the most pertinent items of interest. The final questionnaire was distributed to
      all members of the ACP living or practicing in the United States and members
      engaged in the U.S. armed services. Responses were compiled and analyzed to
      determine correlation of responses using the chi-squared test for count data
      (level of significance alpha = 0.05). Fisher's exact test was applied to all
      significant responses. RESULTS: Surveys were distributed to 1815 ACP members. A
      total of 554 (31%) surveys were completed. On the basis of age distribution of
      survey respondents, it was determined that the respondents were representative of
      the ACP membership. The majority of the respondents (82%; CI, 79% to 85%) treat
      patients with implant-supported prostheses, while 12% (CI, 10% to 15%) surgically
      place implants. Of those not placing implants, 24% reported a desire to place
      implants, while 43% of all respondents expressed a desire for an ACP-sponsored
      course in implant placement. Increased age of the prosthodontist correlated
      negatively with a desire to place implants (p < 0.0001). Dissatisfaction with
      implant placement by others correlates with willingness to surgically place
      implants (p < 0.0001). CONCLUSIONS: Most prosthodontists (82%) use implant
      supported prostheses in their practices, but most of the implants are placed by
      non-prosthodontists. There is general satisfaction with implant placement
      regardless of the specialty of the practitioner placing the implants. Younger
      prosthodontists expressed a greater desire to surgically place implants but were
      not statistically more likely to do so.

PMID- 12237801
TI  - Implant dentistry in predoctoral education: the elective approach.
AB  - In response to interest by dental students and patient needs, an elective program
      in implant dentistry was started at the University of Detroit Mercy School of
      Dentistry (UDM) in the summer of 1994. The 1-year program is offered to a group
      of 10 senior students out of a class of 72. Implant treatment is provided to
      selected edentulous and partially edentulous patients. Predoctoral students
      participate in diagnosis and treatment planning, assist in surgical placement,
      and perform the prosthodontic procedures. A survey was sent to 160 UDM graduates,
      and 90 responded. Out of the 90 respondents, 35% had participated in the elective
      implant program and 65% had not. A Pearson correlation matrix was used to analyze
      their responses. A stronger positive correlation with offering and restoring
      implants was seen in graduates who had completed the elective program in implant
      dentistry.

PMID- 12237802
TI  - Photographing a view of the maxillary anterior teeth with a black background.

PMID- 12237803
TI  - The history of articulators: a critical review of articulators based on geometric
      theories of mandibular movement, part II: Rupert Hall's conical theory.

PMID- 12237805
TI  - Action of Rubus coreanus extract on systemic and local anaphylaxis.
AB  - The effect was investigated of the aqueous extract of Rubus coreanus Miq.
      (Rosaceae) fruits (RCAE) on systemic and local anaphylaxis. RCAE (0.01-1 g/kg)
      dose-dependently inhibited systemic anaphylaxis induced by compound 48/80 in
      mice. RCAE (1 g/kg) also significantly inhibited local anaphylaxis activated by
      anti-DNP IgE. Pretreatment with RCAE at the same concentration before systemic
      anaphylaxis reduced the plasma histamine levels in a dose-dependent manner. RCAE
      (0.001-1 mg/mL) dose-dependently inhibited the histamine release from rat
      peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The
      level of cAMP in RPMC, when RCAE was added, significantly increased, compared
      with that of the normal control. Moreover, RCAE (0.01-1 mg/mL) had a significant
      inhibitory effect on anti-DNP IgE-induced tumour necrosis factor-alpha production
      from RPMC. These results indicate that RCAE may possess antianaphylactic action.

PMID- 12237804
TI  - Cardiovascular effects of Urtica dioica L. in isolated rat heart and aorta.
AB  - Urtica dioica L. or Nettle (Urticaceae) is widely used in oriental Morocco to
      treat hypertension. Aqueous extract of Nettle (AEN) also exerts a hypotensive
      action in the rat in vivo. The aim of this work was to characterize the specific
      cardiac and vascular effects of AEN. In the isolated Langendorff perfused rat
      heart, AEN (1 and 2 g/l) markedly decreased heart rate and increased left
      ventricular pressure. Higher concentration (5 g/l) even led to cardiac arrest.
      Although carbachol mimicked the bradycardiac effect of AEN, atropine (a
      muscarinic receptor antagonist, 1 micro M) did not modify the response. Beside
      its action on myocardium, AEN also affected vascular contractility. Indeed, AEN
      (0.1-5 g/l) produced a dose-dependent increase in basal tone of isolated rat
      aorta. This effect was endothelium independent and was abolished by 1 micro M
      prazosin (an alpha1-adrenergic antagonist). AEN had little additional effects
      when the aorta was precontracted by noradrenaline (1 micro M) or KCl (40 mM). Our
      data indicate that AEN produces a vasoconstriction of the aorta which is due to
      activation of alpha1-adrenergic receptors. However, AEN also induces a strong
      bradycardia through non-cholinergic and non-adrenergic pathways which might
      compensate for its vascular effect and account for the hypotensive action of
      Urtica dioica L described in vivo.

PMID- 12237806
TI  - Evaluation of the effect of triterpenes on urinary risk factors of stone
      formation in pyridoxine deficient hyperoxaluric rats.
AB  - Investigations were carried out to evaluate the efficacy of the pentacyclic
      triterpene, lupeol and its ester, lupeol linoleate, against calcium oxalate
      urolithiasis in rats. Administration of a pyridoxine deficient diet containing 3%
      glycollic acid for 21 days led to increased excretion of stone forming
      constituents such as calcium, oxalate and uric acid. Crystal deposition and
      subsequent renal tubular damage resulted in increased excretion of the tubular
      enzymes alkaline phosphatase, lactate dehydrogenase, gamma glutamyl transferase,
      beta glucuronidase and N-acetyl glucosaminidase along with reduced fibrinolytic
      enzymes. A reduction in the urinary inhibitory factors magnesium and
      glycosaminoglycans was also observed. Treatment with lupeol and lupeol linoleate
      reduced the extent of tubular damage as evidenced from reduced enzymuria and
      minimized the excretion of stone forming constituents.

PMID- 12237807
TI  - Antiinflammatory investigation of some species of Mikania.
AB  - Mikania laevigata Schultz Bip. ex Baker, M. involucrata Hook. et Arn. and M.
      hirsutissima DC. (Asteraceae), commonly occurring in the southern Brazilian State
      of Rio Grande do Sul, were submitted to biological tests to evaluate their
      potential antiinflammatory activity. Decoctions from the leaves and stems were
      analysed by the induced rat paw oedema and pleurisy models. The animals were
      treated orally with different decoction doses. In the induced rat paw oedema
      test, the animals treated with leaf decoctions from M. laevigata (200 mg/ kg) and
      M. involucrata (50 mg/ kg) presented an oedema inhibition of 81.56% and 81.67%,
      respectively, 3 h after the administration of the phlogistic agent. Leaf
      decoctions from M. hirsutissima (400 mg/ kg) did not show such an activity. Stem
      decoctions displayed lower antiinflammatory activity when compared with the same
      doses and response time of the leaf decoctions for all analysed species. In the
      pleurisy assay, leaf decoctions from M. laevigata (400 mg/ kg) and M. involucrata
      (200 mg/ kg) inhibited leukocyte migration to the pleural exudate by 28.26% and
      54.35%, respectively.

PMID- 12237808
TI  - Keishi-bukuryo-gan preserves the endothelium dependent relaxation of thoracic
      aorta in cholesterol-fed rabbit by limiting superoxide generation.
AB  - Formerly, we have reported that keishi-bukuryo-gan prevents the progression of
      atherosclerosis in cholesterol-fed rabbits and inhibits the free radical-induced
      RBC haemolysis in rats. The present study was performed to investigate how keishi
      bukuryo-gan (KBG) inhibits the early stage of atherosclerosis. Plasma lipid
      concentration and hydroxyl radical generation during respiratory burst in
      neutrophils were evaluated at the start and end of the study. The protective
      effect of KBG against endothelium disorder due to hypercholesterolaemia was
      examined. Twelve male Japanese white rabbits (2 kg body weight) were divided into
      two groups. Group A (n = 6) was fed standard rabbit chow containing 1%
      cholesterol for 4 weeks. Group B (n = 6) was fed standard rabbit chow containing
      1% cholesterol and 1% KBG for 4 weeks. In the plasma lipid concentration, only
      the lipid peroxide concentration of group A was significantly higher than that of
      group B. At the end of the study, DMPO-OH, the spin-trapped adduct of hydroxyl
      radicals generated by neutrophils, was increased in both groups, and this
      increase was marked in group B. Endothelium-dependent vasodilatation by
      acetylcholine increased significantly in group B compared with group A. Thus, KBG
      protects the vascular endothelium function by its antioxidative effect and by
      inhibiting the release of free radicals from neutrophils in vivo.

PMID- 12237809
TI  - Antidiarrhoeal activity of seed extract of Albizzia lebbeck Benth.
AB  - The antidiarrhoeal activity of the seed extract of Albizzia lebbeck (Benth.) was
      investigated employing conventional rodent models of diarrhoea, i.e. castor oil
      induced diarrhoea, upper gastrointestinal transit (u.g.t.) and fluid secretion.
      It was found that the aqueous methanol extract of Albizzia lebbeck seeds (2.5-5
      mg/kg i.p.) possessed antidiarrhoeal activity which strengthens the earlier use
      of the seeds in the treatment of diarrhoea and dysentery. The antidiarrhoeal dose
      of the extract was at least 10-30 times less than the LD(50) dose. The extract
      (2.5-5 mg/kg i.p.) potentiated the antidiarrhoeal activity of loperamide (1 mg/kg
      i.p.). Nalaxone (0.5 mg/kg i.p.) significantly inhibited the antidiarrhoeal
      activity of the extract as well as loperamide, thus indicating a role of the
      opioid system in the antidiarrhoeal activity of the extract.

PMID- 12237810
TI  - Effect of the alcohol extract of the seeds of Mucuna pruriens on free radicals
      and oxidative stress in albino rats.
AB  - In vitro and in vivo studies were made with an alcohol extract of the seeds of
      Mucuna pruriens (Fabaceae) to investigate its antioxidant property. In vitro
      studies were carried out in rat liver homogenate to investigate the chemical
      interaction of various phytochemicals with different species of free radicals.
      The effect was also checked on iron-induced lipid peroxidation, oxidation of GSH
      content, and its interaction with hydroxyl and superoxide radicals. There was no
      change on the rate of aerial oxidation of GSH content but it significantly
      inhibited FeSO(4) induced lipid peroxidation. It also inhibited the specific
      chemical reactions induced by superoxides and hydroxyl radicals. The removal of
      these species was through direct chemical interaction. An in vivo study on albino
      rats for 30 days showed no toxic effect up to a dose of 600 mg/kg body weight, on
      oral administration. There was no change in the level of TBA-reactive substances,
      reduced glutathione content and SOD activity in the liver. The activity of serum
      GOT, GPT and alkaline phosphatase was also unchanged. Thus it could be concluded
      that the alcohol extract of the seeds of M. pruriens has an antilipid
      peroxidation property, which is mediated through the removal of superoxides and
      hydroxyl radicals.

PMID- 12237811
TI  - Antioxidative components of Psoralea corylifolia (Leguminosae).
AB  - A meroterpene and four flavonoids were isolated from the seeds of Psoralea
      corylifolia as antioxidative components. Their structures were elucidated by
      spectral data and identified as bakuchiol (1), bavachinin (2), bavachin (3),
      isobavachin (4) and isobavachalcone (5). In particular, meroterpene 1 and
      flavonoids 4 and 5 showed broad antioxidative activities in rat liver microsomes
      and mitochondria. They inhibited NADPH-, ascorbate-, t-BuOOH- and CCl(4)-induced
      lipid peroxidation in microsomes. They also prevented NADH-dependent and
      ascorbate-induced mitochondrial lipid peroxidation. Bakuchiol (1) was the most
      potent antioxidant in microsomes and the inhibition of oxygen consumption induced
      by lipid peroxidation was time-dependent. Furthermore, bakuchiol (1) protected
      human red blood cells against oxidative haemolysis. These phenolic compounds in
      P. corylifolia were shown to be effective in protecting biological membranes
      against various oxidative stresses.

PMID- 12237812
TI  - Effect of quercetin on plasma extravasation in rat CNS and dura mater by ACE and
      NEP inhibition.
AB  - The effects of quercetin on substance P-induced plasma protein extravasation (PE)
      in the rat dura mater, cerebellum, olfactory bulb and cortex and also its
      modulation by endopeptidases, angiotensin-converting enzyme (ACE) and neutral
      endopeptidase (NEP) were studied. PE was assessed by photometric measurement of
      extravasated Evans blue. Substance P (SP) and NEP or ACE inhibitors increased the
      PE in dura mater. Pretreatment with captopril or phosphoramidon potentiated PE
      induced by SP in the dura mater and cerebellum, respectively. Quercetin increased
      the PE in the dura mater, cerebellum and cortex. Further results suggested that
      the PE induced by SP in the dura mater was enhanced by pretreatment with
      quercetin, similar to that observed with selective peptidase inhibitors.
      Quercetin-stimulated extravasation in all tissues was abolished by NK-1 receptor
      blockade. These results suggest that quercetin increases PE in the dura mater and
      CNS tissues by inhibiting NEP and/or ACE, showing that the effect induced in the
      dura mater, cerebellum and cortex occurs through endogenous SP accumulation.

PMID- 12237813
TI  - Screening of selected plant extracts for in vitro inhibitory activity on human
      immunodeficiency virus.
AB  - As part of our screening of anti-AIDS agents from natural sources, extracts of 15
      medicinal plants widely used in the folk medicines of North America and Europe
      were evaluated in vitro. Most of the extracts tested were relatively nontoxic to
      human lymphocytic MT-2 cells, but only the extracts of Hysopp officinalis and
      Dittrichia viscosa exhibited anti-HIV activity in an in vitro MTT assay. The 50%
      hydroalcohol extract of Hysopp officinalis and the aqueous extract of Dittrichia
      viscosa showed inhibitory effects against HIV-1 induced infections in MT-2 cells
      at concentrations ranging from 50 to 100 microg/mL and 25 to 400 microg/mL,
      respectively. Both extracts showed no appreciable cytotoxicity at these
      concentrations.

PMID- 12237814
TI  - Antimicrobial activity of some species of the family Combretaceae.
AB  - Forty eight extracts of four plants of the family Combretaceae were screened for
      antibacterial activity against standard organisms as well as clinical isolates.
      The extracts in different solvent systems showed high activity against both
      standard organisms and clinical isolates. Phytochemical screening revealed that
      the plants were very rich in tannins to which antibacterial activity may be
      attributed.

PMID- 12237816
TI  - Treatment of melasma with Pycnogenol.
AB  - Melasma (or chloasma) is a common disorder of cutaneous hyperpigmentation
      predominantly affecting sun-exposed areas in women. The pathogenesis of melasma
      is not fully understood and treatments are frequently disappointing and often
      associated with side effects. Pycnogenol is a standardized extract of the bark of
      the French maritime pine (Pinus pinaster), a well-known, potent antioxidant.
      Studies in vitro show that Pycnogenol is several times more powerful than vitamin
      E and vitamin C. In addition, it recycles vitamin C, regenerates vitamin E and
      increases the endogenous antioxidant enzyme system. Pycnogenol protects against
      ultraviolet (UV) radiation. Therefore its efficacy in the treatment of melasma
      was investigated. Thirty women with melasma completed a 30-day clinical trial in
      which they took one 25 mg tablet of Pycnogenol with meals three times daily, i.e.
      75 mg Pycnogenol per day. These patients were evaluated clinically by parameters
      such as the melasma area index, pigmentary intensity index and by routine blood
      and urine tests. After a 30-day treatment, the average melasma area of the
      patients decreased by 25.86 +/- 20.39 mm(2) (p < 0.001) and the average
      pigmentary intensity decreased by 0.47 +/- 0.51 unit (p < 0.001). The general
      effective rate was 80%. No side effect was observed. The results of the blood and
      urine test parameters at baseline and at day 30 were within the normal range.
      Moreover, several other associated symptoms such as fatigue, constipation, pains
      in the body and anxiety were also improved. To conclude, Pycnogenol was shown to
      be therapeutically effective and safe in patients suffering from melasma.

PMID- 12237815
TI  - Bioactive phenolic derivatives from Acaena splendens methanol extract.
AB  - Acaena splendens H. et A. has been used in Chilean folk medicine for the
      treatment of fever and inflammation. A description of the in vivo reduction of
      bacterial pyrogen-induced fever in rabbits and carrageenan-induced paw oedema in
      guinea pigs is presented. The methanol extract named ME-1, obtained after
      succesive extractions with petroleum ether and dichloromethane, showed a strong
      antipyretic action (45.7% of effect), though the antiinflammatory activity was
      only observed after submitting this extract to column fractionation, giving a
      crude mixture of flavonoids named C4 with both activities (55.7% and 98.9% of
      antiinflammatory and antipyretic effect respectively at a dose of 600 mg/kg). The
      bioassay-guided fractionation by column chromatography afforded the active
      fraction, which contained (-,-)-epicatechin, tiliroside, 7-O-acetyl-3-O-beta-D
      glucosyl-kaempferol and 7-beta-D-glucosyloxy-5-hydroxy-chromone.

PMID- 12237818
TI  - Protection of DNA and microsomal membranes in vitro by Glycyrrhiza glabra L.
      against gamma irradiation.
AB  - The radioprotective effect of the root extract of Glycyrrhiza glabra L on lipid
      peroxidation in rat liver microsomes and plasmid pBR322 DNA was investigated. The
      extract was found to protect microsomal membranes, as evident from reduction in
      lipid peroxidation, and could also protect plasmid DNA from radiation-induced
      strand breaks.

PMID- 12237817
TI  - Arbutus unedo induces endothelium-dependent relaxation of the isolated rat aorta.
AB  - Arbutus unedo L. (Ericaceae) is used in oriental Morocco to treat arterial
      hypertension. We studied its vasodilator effect and mechanisms of action in
      vitro. The root aqueous extract of Arbutus (0.25 mg/mL) produced a relaxation of
      noradrenaline-precontracted ring preparations of rat aorta with intact
      endothelium. Relaxation by Arbutus did not occur in specimens without endothelium
      and was inhibited by pretreatment with 100 microM N(G)-methyl-L-arginine (L-NMA),
      10 microM methylene blue or 50 microM 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1
      one (ODQ) but not by 10 microM atropine. These results suggest that Arbutus
      produces an endothelium-dependent relaxation of the isolated rat aorta which may
      be mediated mainly by a stimulation of the endothelial nitric oxide synthase by
      mechanisms other than activation of muscarinic receptors.

PMID- 12237819
TI  - A comparative study of different crude extracts of Ocimum sanctum on noise
      stress.
AB  - Our previous studies have shown that the ethanolic extract of Ocimum sanctum (OS)
      leaves was effective in alleviating the noise stress induced changes. Hence in
      this study, we have investigated the effectiveness of different types of crude OS
      extracts on some of the stress parameters after noise stress. The results of this
      study has shown that the active principle responsible for antistressor effect of
      ethanolic extract is also present in cold homogenised leaf extract of OS also.
      Hot extracts slightly decrease the potency of the active principle in normalizing
      corticosteroid level.

PMID- 12237820
TI  - Simple assay for antitumour immunoactive glycoprotein derived from Chlorella
      vulgaris strain CK22 using ELISA.
AB  - A quantitative ELISA system was developed using a monoclonal antibody (MAb)
      specific for an antitumour immunoactive glycoprotein (CVS) derived from C.
      vulgaris strain CK22. The full measuring range of the assay extends from 0.63 to
      10.0 ng/mL of CVS. Although no cross-reaction was observed to proteins tested or
      other biological response modifiers (BRMs) derived from different sources, cross
      reactions were found with culture supernatants from two other strains of C.
      vulgaris having a strong antitumour immunoactivity. Treatment of CVS with
      protease, acid or alkali weakened or completely eliminated the reactivity against
      the MAb and also its antitumour immunoactivities. This ELISA system is suitable
      for the biologically active form of CVS derived from C. vulgaris strain CK22 and
      related immunoactive strains.

PMID- 12237821
TI  - Modulation of serum phosphatases activity in Swiss albino mice against gamma
      irradiation by Mentha piperita Linn.
AB  - The modulatory influence of mentha oil (Mentha piperita Linn.) against a lethal
      dose (8.0 Gy) of gamma irradiation on the activities of serum phosphatases in
      Swiss albino mice was studied at various post-irradiation intervals between 6 h
      and 30 days. Mentha oil (40 microL/animal/day) given orally for 3 consecutive
      days prior to whole-body irradiation (8.0 Gy) showed a modulation of activity of
      serum phosphatases. The values of acid phosphatase activities were significantly
      higher in the irradiated groups throughout the experiment compared with the
      mentha treated unirradiated animals. However, the acid phosphatase activity of
      mentha treated irradiated animals showed a significant decline over untreated
      irradiated animals at all autopsy intervals, which attained the normal value on
      day 5. On the contrary, a marked decrease in serum alkaline phosphatase activity
      was noted in both irradiated groups but in the mentha treated irradiated group
      the values of alkaline phosphatase activity were found to be significantly higher
      than the respective control during the period of study being normal at day 5 post
      irradiation and onwards.

PMID- 12237822
TI  - Glucose lowering efficacy of Ficus racemosa bark extract in normal and alloxan
      diabetic rats.
AB  - The glucose-lowering efficacy of a methanol extract of the stem bark of Ficus
      racemosa Linn. (MEBFR) (Family Moraceae) was evaluated both in normal and alloxan
      induced diabetic rats. The MEBFR at the doses examined (200 and 400 mg/kg p.o.)
      exhibited significant hypoglycaemic activity in both experimental animal models
      when compared with the control group. The activity was also comparable to that of
      the effect produced by a standard antidiabetic agent, glibenclamide 10 mg/kg. The
      present investigation established pharmacological evidence to support the
      folklore claim that it is an antidiabetic agent.

PMID- 12237823
TI  - In vitro immunomodulatory activity of verbascoside from Nepeta ucrainica L.
AB  - Nepeta ucrainica L. is used as a herbal tea in Kazakhistan. Phytochemical
      investigations of the aerial parts of the plant resulted in the isolation of
      verbascoside (1) and 1,5,9-epi-deoxyloganic acid (2). The structures of the
      compounds were elucidated by spectral (UV, IR, (1)H-NMR and (13)C-NMR) methods
      and HPLC analysis. The in vitro immunomodulatory activity of verbascoside was
      investigated by assessing neutrophil function; chemotaxis and intracellular
      killing activity. Verbascoside showed an increased chemotactic activity in all
      doses applied compared with the medium used as a negative control and had a
      positive effect on respiratory burst of neutrophils, but there was an opposite
      effect with increasing doses, pointing to a possible suppression of neutrophil
      intracellular killing activity.

PMID- 12237824
TI  - (+)-Tiliarine, a selective in vitro inhibitor of human melanoma cells.
AB  - Five diphenylbisbenzylisoquinoline (DBBI) alkaloids, tiliacorinine, tiliacorine,
      nor- tiliacorinine A, tiliarine and tiliamosine were isolated from the ethanol
      extract of the roots of Tiliacora racemosa Colebr. and identified by spectral
      techniques. Of these (+)-tiliarine is the only one which exhibited a selective
      inhibitory effect against human melanoma cells (G 361) and had no activity on
      normal human fibroblasts (CCD 974 SK). The activity of (+)-tiliarine against the
      human melanoma cell line was not much modified in the presence of calcium
      chloride.

PMID- 12237827
TI  - Architecture and function of atropisomeric molecular triads.
AB  - Molecular triads, B-A-B, in which the central unit A is aromatic or
      heteroaromatic, can exist as syn or anti conformers or atropisomers of
      correspondingly C or S shape. These stereoisomers are either discrete conformer
      species, often distinguished by NMR spectroscopy, or can be separated at ambient
      temperature as stable atropisomers. In the latter case syn and anti stereoisomers
      exhibit different (e.g., complex-forming) properties. Practical applications of
      atropisomeric triads as ligands in asymmetric dihydroxylation are also discussed.

PMID- 12237828
TI  - Chiral synthesis of secondary alcohols using Geotrichum candidum.
AB  - Chiral synthesis of secondary alcohols of both the (S)- and (R)-enantiomer with
      extremely high enantioselectivities (up to >99% ee) using a biocatalyst,
      Geotrichum candidum, is reviewed. Resting cell and dried-cell preparation using
      acetone were applied to oxidation, reduction, and deracemization reactions. Many
      methods to improve the reactivity and enantioselectivity of the reactions were
      developed. For example, additives such as secondary alcohols and hydrophobic
      resin (Amberlite XAD) were used in nonaqueous reaction media such as organic and
      supercritical solvents as well as in aqueous ones. As a result, optically pure
      alcohols of both enantiomers were synthesized on a gram scale.

PMID- 12237829
TI  - Practical asymmetric synthetic route to 4,4,4-trifluoro-3-hydroxybutyrate: head
      to-tail and head-to-head crystallizations through double and single hydrogen
      bonds of hetero- and homochiral 4,4,4-trifluoro-3-hydroxybutyrophenones.
AB  - A practical asymmetric synthetic route to 4,4,4-trifluoro-3-hydroxybutyrophenone
      and the butyric acid phenyl ester is described using heterochiral crystallization
      through double hydrogen bonding assembly in head-to-tail fashion and sequential
      Baeyer-Villiger oxidation reaction by trifluoroperacetic acid.

PMID- 12237830
TI  - Enantiomeric recognition of amino acids using a chiral spiropyran derivative.
AB  - An optically active spiropyran 1 with a binaphthol moiety as a chiral source was
      synthesized. The colored merocyanine form of (R)-1 obtained by the UV irradiation
      remained in the presence of D-amino acids longer than with L-amino acids.

PMID- 12237831
TI  - Enantioselective addition of diethylzinc to aldehydes catalyzed by optically
      active C2-symmetrical bis-beta-amino alcohols.
AB  - The syntheses of new optically active C(2)-symmetrical bis-beta-amino alcohols 1
      6 from (S)-2-(1-hydroxy-1,1-diphenylmethyl)-pyrrolidine are described. Especially
      attention is focused on bridges, which link the two beta-amino alcohol units.
      These new chiral ligands have been successfully applied in the catalytic
      enantioselective addition of diethylzinc to aldehydes to give sec-alcohols in
      good yields with up to 95% enantiomeric excess.

PMID- 12237832
TI  - Synthesis of a novel photoresponsive axially chiral phosphine ligand containing
      an arylazo group and its application to palladium-catalyzed asymmetric allylic
      alkylation.
AB  - Novel photoresponsive axially chiral monophosphine ligands containing azobenzene
      moiety were prepared and applied to a palladium-catalyzed allylic alkylation. The
      reaction of rac-1,3-diphenyl-2-propenyl acetate gave the alkylated products with
      up to 90% enantiomeric excess. The ligand exhibited a trans to cis
      photoisomerization upon irradiation with UV light.

PMID- 12237833
TI  - Exo-selective asymmetric Diels-Alder reaction of acrylate ester.
AB  - Diels-Alder reaction of 2-acryloyloxy-2'-(2-pyridylazo)-1,1'-binaphthyl with
      cyclopentadiene in the presence of an equimolar amount of tin(IV) chloride showed
      unusual exo-selectivity with a high degree of diastereofacial differentiation.

PMID- 12237834
TI  - Determination of the plasma levels of metyrapone and its enantiomeric metyrapol
      metabolites by direct plasma injection and multidimensional achiral-chiral
      chromatography.
AB  - The development and validation of a direct injection high-performance liquid
      chromatographic (HPLC) method, with column switching, for the determination of
      metyrapol enantiomers and metyrapone in human plasma is described. The system
      used in this work was composed of a restricted access media (RAM) bovine serum
      albumin (BSA) octyl column coupled to an amylose tris(3,5
      dimethoxyphenylcarbamate) chiral column. Water was used as eluent for the first 5
      min at a flow rate of 1.0 ml/min for the elution of the plasma proteins and then
      acetonitrile-water (30:70 v/v) for the transfer and analysis of metyrapol
      enantiomers and metyrapone, which were detected by UV at lambda = 260 nm. The
      total analysis time was about 32 min. The calibration curves for each enantiomer
      and for the metyrapone were linear in the ranges 0.075-0.75 microg/ml and 0.150
      1.50 microg/ml, respectively. Recoveries, intra- and interday precision and
      accuracy were determined using three quality controls, one low (0.18 microg/ml),
      one medium (0.75 microg/ml), and one high (1.35 microg/ml) plasma concentration.
      Quantitative recoveries and good precision and accuracy were obtained. The limit
      of quantitation were 0.045 microg/ml for both enantiomers and for the metyrapone.

PMID- 12237835
TI  - Protein binding of indobufen enantiomers: pharmacokinetics of free fraction
      studies after single or multiple doses of rac-indobufen.
AB  - The binding of the enantiomers of indobufen (INDB) to human serum proteins was
      investigated using the racemic mixture or the pure (+)-S-enantiomer in a
      concentration range of 2.5-100.0 mg/L. In addition, the pharmacokinetics of free
      (unbound) and total INDB enantiomers were studied 1) following administration of
      a single 200 mg rac-INDB tablet to healthy volunteers, and 2) in obliterative
      atherosclerosis patients at steady state. The free fraction of INDB was obtained
      by ultrafiltration. Using the racemic mixture, the binding parameters of the two
      enantiomers were different, showing enantioselectivity in protein binding. The (
      )-R-enantiomer was bound more strongly to human serum albumin, with association
      constant K = 11.95 +/- 0.98 x 10(5) M(-1) and n = 0.72 +/- 0.02 binding sites.
      The comparable data for the (+)-S-enantiomer were K = 4.65 +/- 0.02 x 10(5) M(
      1), n = 0.92 +/- 0.01. When the binding of (+)-S-enantiomer was studied alone,
      the association constant K (2.10 +/- 0.18 x 10(5) M(-1)) was lower and the number
      of binding sites was increased, to n = 1.87 +/- 0.17. Competition occurred
      between the enantiomers, with the (-)-R-enantiomer displacing its antipode. The
      fraction of both enantiomers bound to serum proteins was 99.0%, which increased
      with decreasing initial concentration of the enantiomers. In healthy volunteers
      the (+)-S-enantiomer was eliminated faster than its (-)-R antipode, resulting in
      a lower AUC for the (+)-S-enantiomer. Significant differences were observed in
      the total INDB enantiomer concentrations. The mean unbound fraction of (-)-R- and
      (+)-S-INDB was 0.45% and 0.43%, respectively. Levels of the free (+)-S-enantiomer
      were higher than its (-)-R-antipode at steady state in patients with obliterative
      atherosclerosis who also took other drugs. The free enantiomer fraction increased
      to around 1% upon repeated administration. We conclude that the more rapid
      elimination of the (+)-S enantiomer is associated with its weaker binding to
      serum proteins.

PMID- 12237836
TI  - Use of online-dual-column extraction in conjunction with chiral liquid
      chromatography tandem mass spectrometry for determination of terbutaline
      enantiomers in human plasma.
AB  - An online sample extraction chiral bioanalytical method was developed and
      validated for the quantification of terbutaline, a beta2-selective adrenoceptor
      agonist, spiked into human plasma by using two extraction columns and a chiral
      stationary phase (CSP) in conjunction with liquid chromatography tandem mass
      spectrometry (LC-MS/MS). In this method, two Oasis HLB extraction columns were
      used in parallel for plasma sample purification and a Chirobiotic T CSP was used
      for enantiomeric separation. Atmospheric pressure chemical ionization MS/MS was
      employed in multiple reaction monitoring mode for the detection and
      quantification. Subsequent to the addition of an internal standard solution, the
      plasma samples were directly injected onto the system for extraction and
      analysis. This method allowed the use of one of the extraction columns for
      purification while the other was being equilibrated. Hence, the time required for
      reconditioning the extraction columns did not contribute to the total analysis
      time per sample, which resulted in a shorter run time and higher throughput. A
      lower limit of quantification of 1.0 ng/mL was achieved using only 50 microliter
      of human plasma. The method was validated with a dynamic range of 1.0-200 ng/mL.
      The intra- and interday precision was no more than 11% CV and the assay accuracy
      was between 94-106%.

PMID- 12237837
TI  - Reflectance circular dichroism of solid-state chiral coordination compounds.
AB  - Solid-state diffuse reflectance circular dichroism (DRCD) spectra of some chiral
      lambda- and delta-M[(A--A)(n)](m+) coordination compounds [M(III) = Cr, Co; A--A
      = ethylendiamine (en), O,O'-2(R)3(R)dimethylethylene dithiophosphate ion,
      (R,R)bdtp(-), sepulchrate (Sep); n = 1, 3; m = 0, 3] were measured and compared
      with their solution, nujol mull, and KBr pellet spectra in the spectral region of
      300-800 nm. The validity of the DRCD method to obtain reliable CD spectra which
      reflect a correct absolute configuration at the metal coordination center as well
      as subtle changes in the stereochemistry of the compound in the solid vs.
      solution states was proved. DRCD is the only spectroscopic method to examine
      randomly oriented chiral compounds without the effect of pressure, solvent, or
      diluting media such as KBr or nujol (which lends the sample irrecoverable and may
      interact with the sample), and directly relate to the structure that is revealed
      by X-ray diffractometry.

PMID- 12237839
TI  - Chloride/anion channels in glial cell membranes.
AB  - At least seven different chloride/anion currents have now been identified in
      astrocytes, oligodendrocytes/Schwann cells, and microglia. Only for two of these
      currents is the corresponding gene known. One of these genes is not encoding for
      a chloride channel, but for a class of mitochondria-like pores also found in cell
      membranes. Astrocytes and oligodendrocytes differ in their resting properties:
      astrocytes accumulate chloride but do not have a significant permeability.
      Oligodendrocytes have a close to passive distribution and a significant
      permeability. Under certain circumstances, astrocytes can express a resting
      chloride conductance. Reactive and neoplastic astrocytes as well as astrocytes
      with an altered shape exhibit a resting conductance. The function of these
      channels certainly involves volume regulation. Other possible functions are
      potassium homeostasis, migration, proliferation (in microglia), and involvement
      in spreading depression waves. Of greatest interest are two phenomena discovered
      in situ: The ClC-2 channel is only found in astrocytic endfeet near blood
      capillaries adjacent to neuronal GABA(A) receptors. In the supraoptic nucleus of
      the hypothalamus, there is an osmosensitive astrocytic taurine release. This
      released taurine interacts with glycine receptors in neighboring neurons, causing
      inhibition. It is assumed that with the future availability of more in situ,
      rather than in vitro, studies, an increased number of such complex interactions
      between glial cells, neurons, and blood vessels will be discovered.

PMID- 12237840
TI  - Differential expression of protein tyrosine kinase genes during microglial
      activation.
AB  - Protein tyrosine kinase (PTK) activity is abundant in microglia, but the PTKs
      that participate in their activation have not been identified. For these studies,
      we used three paradigms to characterize PTK expression during microglial
      activation: resting and activated microglia were bulk fractionated from the adult
      brain, cultured newborn microglia were treated with lipopolysaccharide (LPS) to
      model the transition from activated toward phagocytic microglia, and PTK
      expression was examined in activated microglia in situ after facial nerve
      axotomy. Two PCR-based strategies were used to show that 21 different PTK genes
      are expressed by rat brain microglia: 5 receptor PTKs, 10 nonreceptor PTKs, and 6
      members of the src family. Seven of the 21 PTKs were examined in greater detail.
      Five PTK mRNAs (fgr, hck, fak, jak-2, and flk-1) increased expression across all
      three models of activation. We conclude that they represent key components in the
      cascades that participate in microglial activation. In contrast, expression of
      fes and fms correlated with stimuli that affect microglial proliferation. Four of
      the PTKs (hck, fgr, fes, and fms) are believed to be myeloid cell specific and
      were not expressed by cultured astrocytes. HCK and FAK protein were also not
      expressed in lysates of immature astrocytes and oligodendrocytes. Because of
      their putative specificity, these kinases represent potential targets for
      inhibitors of microglial activation. Because reactive microglia can exacerbate
      the severity of neurological diseases, the identification of specific kinases
      that participate in microglial activation represents an important advance toward
      the development of new therapeutics.

PMID- 12237841
TI  - Oligodendrocyte and astrocyte development in rodents: an in situ and
      immunohistological analysis during embryonic development.
AB  - Lineally related multipotent neuroepithelial cells (NEP), neuronal restricted
      precursors (NRP), and glial restricted precursors (GRP) have been identified in
      the spinal cord. To determine the sequence of differentiation and identify
      lineage and stage-specific markers, we have examined the spatiotemporal
      expression of established glial markers during rodent embryonic development and
      within fetal cell culture. In this report, we show that proliferating stem cells
      in the developing neural tube do not express any glial markers at E10.5. By E11,
      however, glial precursors have begun to differentiate and at least two regions of
      the ventral neural tube containing glial precursor cells can be distinguished, an
      Nkx2.2/Neurogenin 3 (Ngn3) domain and a platelet-derived growth factor receptor
      alpha (PDGFRalpha)/Olig2/Sox10 domain. Radial glia, as identified by RC1
      immunoreactivity, develop in concert with other glial precursors and can be
      distinguished by their morphology, spatial distribution, and antigen expression.
      Astrocytes as assessed by glial fibrillary acidic protein (GFAP) immunoreactivity
      are first detected at E16. A novel dorsal domain of CD44 immunoreactivity that
      can be distinguished from the more ventral glial precursor domains can be
      detected as early as E13.5.

PMID- 12237842
TI  - Poly(ADP-ribose) polymerase inhibitor increases growth inhibition and reduces
      G(2)/M cell accumulation induced by temozolomide in malignant glioma cells.
AB  - Temozolomide (TZM) is a novel methylating agent currently under investigation for
      treatment of recurrent high-grade gliomas. Although TZM generates a wide spectrum
      of methyl adducts, its cytotoxicity has been attributed to mismatch repair (MR)
      mediated processing of O(6)-methylguanine:T mispairs. N3-methyladenine and N7
      methylguanine adducts are promptly repaired by the base excision repair system,
      unless a poly(ADP-ribose) polymerase (PARP) inhibitor is combined to TZM. In this
      case, the repair process of N-methylpurines cannot be completed and the deriving
      DNA strand breaks contribute to cytotoxicity. In this study, we investigated the
      influence on cell growth and cell cycle of treatment with TZM + PARP inhibitor in
      glioma cells characterized by different susceptibility to TZM. The results
      indicated that PARP inhibitor increases growth inhibition induced by TZM in
      either p53-wild-type or p53-mutant glioblastoma cells, as early as 24 h after
      drug exposure. The enhancing effect exerted by PARP inhibitor was particularly
      evident in glioma cells characterized by a defective expression of MR, since
      these cells are tolerant to O(6)-methylguanine damage and show low sensitivity to
      TZM. In O(6)-alkylguanine-DNA alkyltransferase (OGAT)-deficient and MR-proficient
      tumor cells bearing wild-type p53, the drug combination markedly reduced cell
      accumulation in the G(2)/M phase of cell cycle and induction of the G(2)
      checkpoint regulator Chk1 kinase. In short-term cultures of glioma cells derived
      from surgical specimens, PARP inhibitor enhanced chemosensitivity to TZM and this
      effect was especially evident in OGAT-proficient tumors. Thus, a pharmacological
      strategy based on the interruption of N-methylpurine repair might represent a
      novel strategy to restore or increase glioma sensitivity to TZM.

PMID- 12237843
TI  - Extracellular and intracellular regulation of oligodendrocyte development: roles
      of Sonic hedgehog and expression of E proteins.
AB  - Recent advances in understanding oligodendrocyte development have revealed the
      importance of both extra- and intracellular molecules in regulating the
      induction, survival, and proliferation of early oligodendrocyte progenitors. The
      signaling molecule Sonic hedgehog (Shh) is critical for normal development of
      oligodendrocytes, although the precise influences of Shh on cells of the
      oligodendrocyte lineage are unclear. The present study shows that Shh increased
      the number of oligodendrocyte precursors in both pure cultures of oligodendrocyte
      precursors and mixed cultures from embryonic rat spinal cord. In pure precursor
      cultures Shh increased cell survival. In mixed cultures, Shh increased both the
      survival and proliferation of oligodendrocyte precursors in a concentration
      dependent manner. One intracellular consequence of exposure to Shh is the
      activation of transcription factors in oligodendrocyte lineage cells, which are
      critical for oligodendrocyte development, helix-loop-helix (HLH) transcription
      factors, Olig1 and 2. In many cases, HLH proteins such as Olig1 and Olig2
      heterodimerize with other HLH proteins, such as members of the E subfamily, which
      are critical regulators of cell proliferation and differentiation. Immature
      (A2B5(+)) and more mature (O4(+)) rat oligodendrocyte precursors in dissociated
      cell culture expressed Olig1 as well as E proteins, HEB and E2A. Similarly, cells
      bearing the morphology of oligodendrocyte precursors expressed both Olig1 and HEB
      or E2A. We propose that E2A and/or HEB, possibly in combination with Olig1 and 2,
      are critical components of oligodendrogenesis and may regulate cell survival,
      proliferation, and fate decisions in the oligodendrocyte lineage.

PMID- 12237844
TI  - Characterization of A2B5+ glial precursor cells from cryopreserved human fetal
      brain progenitor cells.
AB  - The identification and characterization of human neural precursor cells are
      critical in extending our understanding of central nervous system development
      from model animal systems to our own species. Moreover, availability of well
      characterized populations of human cells is of potential value in endeavors
      ranging from cell transplantation to drug screening. We have isolated a
      population of continuously dividing glial-restricted precursor cells from
      commercially available cryopreserved 18-20 weeks old fetal brain neural
      progenitor cells. These human glial-restricted precursor cells are A2B5(+) and do
      not express polysialylated E-NCAM (PSA-NCAM). They can be grown as purified
      populations in serum-free medium supplemented with basic fibroblast growth factor
      (bFGF) and can be induced to generate cells with the antigenic characteristics of
      oligodendrocytes and distinct astrocytic populations.

PMID- 12237845
TI  - Muller cells in allogeneic adult rabbit retinal transplants.
AB  - Muller cell morphology and degree of activation in adult retinal transplants
      have, to our knowledge, never been reported previously. We transplanted adult
      rabbit neuroretinal full-thickness sheets, prepared under strict control, to the
      subretinal space of adult rabbits. After surviving 6-174 days, eyes were examined
      in the light microscope, and grafts displaying the normal laminated morphology
      were labeled with antibodies against vimentin and glial fibrillary acidic protein
      (GFAP). Muller cells in the grafts displayed the normal vertical arrangement,
      from outer limiting membrane to vitread endfeet. They showed an initial degree of
      activation, evident by GFAP upregulation, which diminished with increasing
      survival times, and was absent in the oldest specimens. In the host retina,
      Muller cells in the transplant area became progressively more disorganized with
      increasing survival times, and their degree of activation increased. Our results
      suggests that adult full-thickness neuroretinal grafts are structurally stable,
      even in long-term specimens, and thrive in spite of their allogeneic environment.
      The gliotic change seen in the host retina covering the graft is identical to the
      one seen in earlier reported eyes receiving embryonic grafts, and is due to the
      merangiotic nature of the rabbit neuroretina.

PMID- 12237846
TI  - p16(ink4a) and retinoic acid modulate rhoA and GFAP expression during induction
      of a stellate phenotype in U343 MG-A astrocytoma cells.
AB  - We previously showed that the expression of p16(ink4a) (p16), in conjunction with
      retinoic acid (RA) treatment in the p16-deficient astrocytoma cell line, U343 MG
      A, induced a potent cell cycle arrest in G(1) associated with changes in
      morphology. In this study, we investigated the effects of p16 expression and RA
      treatment on the expression and distribution of actin, glial fibrillary acidic
      protein (GFAP), and vimentin within the U343 MG-A astrocytoma cytoskeleton.
      Changes in expression and location of the small GTPase, rhoA, were also examined
      after p16 expression and RA treatment. We showed that p16 expression and RA
      treatment led to an increase in the expression of GFAP, as well as its
      reorganization but that it did not significantly affect actin or vimentin
      expression. p16 induction in combination with RA treatment resulted in a
      decreased expression and activation of rhoA as determined by immunocytochemistry
      and Western blot analysis of soluble and insoluble fractions of cell lysates.
      Endogenous levels of rhoA expression varied among samples in a panel of
      astrocytoma cell lines as determined by Western blot analysis. Introduction of a
      dominant active rhoA mutant into p16-induced, RA-treated U343 MG-A astrocytoma
      cells was associated with the loss of long astrocytic processes and stellate
      morphology. These data are among the first to report the pattern of rhoA
      expression in human astrocytoma cell lines. They furthermore suggest that the
      stellate cell phenotype observed in U343 MG-A astrocytoma cells after cyclin
      dependent kinase inhibitor (CKI) induction and RA treatment is accompanied by an
      inhibition and inactivation of rhoA in this cell system.

PMID- 12237847
TI  - TGF-beta induces cell death in the oligodendroglial cell line OLI-neu.
AB  - We have shown that TGF-beta plays an important role during the period of
      developmental cell death in the nervous system. Immunoneutralization of TGF-beta
      prevents ontogenetic neuron death in vivo. Like neurons, oligodendrocytes are
      generated in excess and eliminated by apoptosis. It has been shown that
      oligodendrocyte progenitors and newly formed oligodendrocytes are especially
      susceptible to apoptosis. We choose the oligodendrocyte precursor cell line OLI
      neu to address the question if TGF-beta could play a role for the control of
      oligodendrocyte proliferation and cell death. Flow cytometric analysis revealed
      that OLI-neu cells arrested in the G1 phase of the cell cycle underwent apoptosis
      in response to TGF-beta. TUNEL assays, apoptosis ELISA, and caspase assays
      substantiated the finding that OLI-neu cells died after TGF-beta treatment. Cell
      death could be inhibited by application of pan-caspase or caspase 8 and 9
      inhibitors, whereas the inhibition of calpain was unaffected. Furthermore, we
      found a reduction of bcl-X(L) at the protein as well as at the mRNA level, while
      p27 was upregulated. The Smad cascade was activated while TGF-beta reduced the
      activity of the p42/p44 MAP kinase pathway. Together, these data show that TGF
      beta induced apoptotic cell death in cells of oligodendroglial origin, whereby
      the signaling cascade involved the downregulation of antiapoptotic signaling such
      as bcl-X(L) leading to the activation of caspases.

PMID- 12237848
TI  - Transforming growth factor beta1 prevents IL-1beta-induced microglial activation,
      whereas TNFalpha- and IL-6-stimulated activation are not antagonized.
AB  - Microglia rapidly respond to CNS injury, yet the mechanisms leading to their
      activation and inactivation remain poorly defined. In particular, few studies
      have established how interactions between inflammatory mediators affect the
      innate immune response of microglia. To begin to establish how microglia
      integrate signals from multiple inflammatory mediators, we examined the effects
      of interleukin 1beta (IL-1beta), interleukin 6 (IL-6), tumor necrosis factor
      alpha (TNFalpha), interferon gamma (IFN-gamma), and transforming growth factor
      beta1 (TGFbeta1) on both newborn and bulk-isolated adult microglia. To assess the
      functional state of the cells, we assayed the expression of cyclooxygenase 2 (Cox
      2), interleukin 6, and tumor necrosis factor alpha, and two protein tyrosine
      kinases that have been implicated in microglial responses to activational
      stimuli, HCK and FAK. These studies demonstrated that IL-1beta, TNFalpha, IL-6,
      but not IFN-gamma increase the expression of Cox-2, whereas they all increase the
      expression of HCK and FAK. In these studies, TGFbeta1 either had no effect, or it
      decreased basal levels of these proteins. TGFbeta1 blocked activation by IL-1beta
      when given prior to, or simultaneously with, IL-1beta. TGFbeta1 blocked the
      induction of the tyrosine kinases, Cox-2, and the induction of IL-6 and TNFalpha
      mRNAs. However, TGFbeta1 was ineffective in antagonizing the induction of Cox-2
      by either IL-6 or TNFalpha. We conclude that the TGFbeta receptor signaling
      cascades intersect with IL-1, but they may not interact with IL-6 or TNFalpha
      signaling pathways that lead to activation.

PMID- 12237849
TI  - The relative number of macrophages/microglia expressing macrophage colony
      stimulating factor and its receptor decreases in multiple sclerosis lesions.
AB  - The activation of macrophages/microglia in multiple sclerosis (MS) lesions plays
      a central role in the effector phase of myelin breakdown. The precise patterns of
      macrophage/microglia activation during demyelination have not yet been defined.
      The growth and activating factor macrophage-colony stimulating factor (M-CSF) and
      its specific receptor (M-CSFR) may be involved in this process. The present study
      investigated the expression of M-CSF and M-CSFR mRNA by in situ hybridization in
      60 lesions from 32 MS patients. In the control and periplaque white matter,
      microglia was almost completely M-CSFR positive. Irrespective of the
      demyelinating activity, an increased number of cells expressed M-CSF or M-CSFR
      mRNA within the lesions. However, despite the tremendous increase in
      macrophages/microglia within the lesions, the relative number of these cells
      expressing M-CSF or M-CSFR decreased. There was no correlation of M-CSF or M-CSFR
      expression with active myelin breakdown. The correlation between the clinical
      course and the expression of M-CSF or M-CSFR mRNA revealed significant
      differences with the lowest expression in primary progressive MS. These results
      suggest a downregulation of M-CSF and M-CSFR inside the MS plaque probably due to
      the high amount of macrophage-derived cytokines or mediators. Nevertheless, the
      differences in the relative number of cells expressing the M-CSF/M-CSFR pathway
      implicate that this pathway may be an important contributory factor in different
      forms of MS pathology.

PMID- 12237851
TI  - Actin patch assembly proteins Las17p and Sla1p restrict cell wall growth to
      daughter cells and interact with cis-Golgi protein Kre6p.
AB  - The cytoplasmic tail of Kre6p, a Golgi membrane protein involved in cell wall
      synthesis, interacts with the actin patch assembly components Las17p and Sla1p in
      a two-hybrid assay, and Kre6p co-immunoprecipitates with Las17p. Kre6p showed
      extensive co-localization with Och1p-containing cis-Golgi vesicles. The correct
      localization of Kre6p requires its cytoplasmic tail, Las17p, Sla1p and Vrp1p,
      suggesting that the cytoplasmic tail of Kre6p acts as a receptor, linking this
      cis-Golgi protein to Las17p and Sla1p. The actin patch assembly mutants las17
      delta, sla1delta and vrp1 delta showed elevated levels of cell wall beta-1,6
      glucan, and mutant cells were capable of only a limited number of cell divisions
      compared to wild-type. EM image analysis and beta-1,6-glucan localization
      indicated abnormal wall proliferation in the mother cells of these mutants. The
      pattern of cell wall hypertrophy indicates a failure to restrict cell wall growth
      to the bud.

PMID- 12237852
TI  - Maintenance of cell integrity in the gas1 mutant of Saccharomyces cerevisiae
      requires the Chs3p-targeting and activation pathway and involves an unusual Chs3p
      localization.
AB  - Chitin synthase III is essential for the increase in chitin level and for cell
      integrity in cells lacking Gas1p, a beta(1,3)-glucanosyltransferase. In order to
      discover whether the upregulation of chitin synthesis proceeds through the
      canonical transport and activation pathway of Chs3p or through an alternative
      one, here we studied the effects of the inactivation of the GAS1 and CHS4-5-6-7
      genes. All the double-null mutants showed a temperature-sensitive cell lysis
      phenotype that could be suppressed by the presence of an osmotic stabilizer. In
      liquid YEPD at 30 degrees C, chs4 delta gas1 delta, chs5 delta gas1 delta, chs6
      deltagas1 delta and chs7 delta gas1 delta mutants were unable to grow, whereas
      they grew very slowly in minimal medium and showed low viability. High osmolarity
      suppressed the defective phenotype and restored growth. In chs4 gas1, chs5 gas1
      and chs7 gas1, chitin levels did not increase and were reduced to only 10%, while
      in chs6 gas1 the value of gas1 was reduced to 20-40%. To investigate at which
      level the upregulation of chitin synthesis could occur, mRNA levels were
      monitored. The expression of CHS4-5-6-7 did not change significantly in gas1
      delta. In strains expressing HA-tagged forms, the localization of Chs3p and Chs5p
      was examined. In the gas1 mutant the fluorescence pattern was affected and the
      proteins appeared abnormally present in the bud. The results indicate that: (a)
      the function of the CHS4-7 genes is required for chitin hyperaccumulation in gas1
      mutant and for cell integrity; (b) homologous genes do not replace their
      function; (c) the regulation of CHS4-7 genes does not occur at transcriptional
      level. Control of the position of chitin synthesis could be important in
      protecting the bud from lysis.

PMID- 12237853
TI  - What similarity between human and fission yeast proteins is required for
      orthology?

PMID- 12237854
TI  - Cloning and characterization of WMSU1, a Williopsis saturnus var. mrakii gene
      encoding a new yeast SUN protein involved in the cell wall structure.
AB  - SUN proteins of Saccharomyces cerevisiae have been defined on the basis of high
      homologies in their C-terminal domain. Recently, two of these four proteins were
      shown to be involved in cell wall morphogenesis (Mouassite et al., 2000a). In the
      present study, we have isolated WMSU1 (Accession No. AF418983), a new SUN-related
      gene, from W. saturnus var. mrakii MUCL 41968. Sequencing of the gene revealed an
      open reading frame coding for 402 amino acids. The predicted amino acid sequence
      of WMSU1 is closely related to the S. cerevisiae SUN proteins and to other yeast
      proteins involved in cell wall metabolism. WMSU1 is proposed to encode a cell
      wall protein since its predicted product contains a signal sequence, a Kex2p
      cleavage site and a serine/threonine-rich N-terminal domain. Southern blot
      analysis of the W. saturnus var. mrakii MUCL 41968 genome using the highly
      conserved domain of WMSU1 as a probe suggested that the isolated gene belongs to
      a multigenic family. Expression of WMSU1 in E. coli led to a 45 kDa protein,
      which appeared to be toxic to this host. Scanning electron microscopy analysis of
      a recombinant S. cerevisiae producing Wmsu1p showed that this strain exhibited an
      altered cell wall, thus pointing to a probable role of this protein in the cell
      wall structure.

PMID- 12237855
TI  - Genome-wide search of Schizosaccharomyces pombe genes causing overexpression
      mediated cell cycle defects.
AB  - Genetic studies in yeasts enable an in vivo analysis of gene functions required
      for the cell division cycle (cdc genes) in eukaryotes. In order to characterize
      new functions involved in cell cycle regulation, we searched for genes causing
      cell division defects by overexpression in the fission yeast Schizosaccharomyces
      pombe. By using this dominant genetic strategy, 26 independent clones were
      isolated from a Sz. pombe cDNA library. The cloned cDNAs were partially sequenced
      and identified by computer analysis. The 26 clones isolated corresponded to 21
      different genes. Among them, six were genes previously characterized in Sz.
      pombe, 11 were homologues to genes identified and characterized in other
      organisms, and four represented genes with unknown functions. In addition to
      known cell cycle regulators encoding inhibitory protein kinases (wee1, pka1) and
      DNA checkpoint proteins (Pcna, rad24), we have identified genes that are involved
      in a number of cellular processes. This includes protein synthesis (ribosomal
      proteins L7, L10, L29, L41, S6, S11, S17 and the PolyA-Binding Protein PABP),
      protein degradation (UBI3), nucleolar rRNA expression (fib, imp1, dbp2), cell
      cytoskeleton (act1) and glycolysis (pfk1). The interference caused in the cell
      cycle by overexpression of these genes may elucidate novel mechanisms coupling
      different cellular processes with the control of the cell division. The effect
      caused by some of them is described in more detail.

PMID- 12237856
TI  - A cell surface display system using novel GPI-anchored proteins in Hansenula
      polymorpha.
AB  - A cell surface display system was developed in yeast Hansenula polymorpha. The
      four genes HpSED1, HpGAS1, HpTIP1and HpCWP1, encoding glycosylphosphatidyl
      inositol (GPI)-anchored cell surface proteins from H. polymorpha, were cloned,
      characterized and evaluated for their efficacies as cell surface display motifs
      of reporter proteins. Sequence analysis of these genes revealed that each encodes
      a typical GPI-anchored protein that is structurally similar to a counterpart gene
      in S. cerevisiae. The genes showed a high content of serine-threonine (alanine)
      and harboured a putative secretion signal in the N-terminus and the GPI
      attachment signal in the C-terminus. The surface anchoring efficiency of these
      putative cell surface proteins was tested by fusion to the C-terminal of
      carboxymethylcellulase (CMCase) from Bacillus subtilis. In all cases, high CMCase
      activities were detected in intact cell fraction, indicating anchoring of CMCase
      to the cell surface. HpCwp1p, HpGas1p and the 40 C-terminal amino acids of
      HpTip1p from H. polymorpha exhibited a comparatively high CMCase surface
      anchoring efficiency. When these proteins were used as anchoring motifs for
      surface display of the glucose oxidase (GOD) from Aspergillus niger, most enzyme
      activity was detected at the cell surface. Fluorescence activated cell sorter
      (FACS) analysis of cells displaying GOD on the cell surface demonstrated that GOD
      was well exposed on the cell surface. HpCwp1p showed the highest anchoring
      efficiency among others.

PMID- 12237857
TI  - Molecular cloning and sequence analysis of the Zygosaccharomyces bailii HIS3 gene
      encoding the imidazole glycerolphosphate dehydratase.
AB  - Zygosaccharomyces bailii is a spoilage yeast belonging to the Zygosaccharomyces
      genus. In recent years these yeasts, due to their exceptional resistance to
      several stresses, have become more and more interesting as model organisms to
      study the molecular basis of the said resistance. A Z. bailii cDNA library has
      been built and the 672 bp nucleotide sequence coding for the HIS3 gene was cloned
      by complementation of a Saccharomyces cerevisiae his3 mutant strain. The deduced
      223 amino acid sequence shares a high degree of homology with His3p homologues in
      other non-conventional yeast species. The GeneBank Accession No. is AY050224.

PMID- 12237858
TI  - Cloning and analysis of CoEXG1, a secreted 1,3-beta-glucanase of the yeast
      biocontrol agent Candida oleophila.
AB  - Lytic enzymes may have a role in the biological control of fungi. The yeast
      biocontrol agent, Candida oleophila, is an excellent subject to research this
      matter. In the present study, CoEXG1, which encodes for a secreted 1,3-beta
      glucanase, is the first gene to be cloned from C. oleophila. It was isolated from
      a partial genomic library and analysed. Its open reading frame and putative
      promoter were expressed in baker's yeast, Saccharomyces cerevisiae. The reading
      frame, expressed under the inducible GAL1 promoter, caused an increased secretion
      of beta-glucanase, and the putative promoter region activated the lacZ reporter
      gene, to which it was fused. Sequencing analysis revealed that CoEXG1 carries the
      signature pattern of the 5 glycohydrolases family and has a putative secretion
      leader, as well as a high degree of identity to yeast 1,3-beta-glucanases. The
      GenBank Accession No. of CoEXG1 is AF393806.

PMID- 12237859
TI  - Role of reactive oxygen species in hippocampal long-term potentiation:
      contributory or inhibitory?
AB  - Reactive oxygen species (ROS) typically are characterized as molecules involved
      in neurotoxicity and neurodegeneration. However, recent evidence from both
      neuronal and nonneuronal cells suggests that ROS also function as small messenger
      molecules that are normal components of signal transduction cascades during
      physiological processes. Consistent with this idea, ROS have been shown to be
      critical for hippocampal long-term potentiation (LTP), a form of synaptic
      plasticity widely studied as a cellular substrate for learning and memory. On the
      other hand, ROS also have been shown to be involved in aging-related impairment
      of LTP. This review discusses the evidence supporting the notion that ROS both
      contribute to normal LTP and are involved in age-related impairment of LTP. We
      also discuss possible sources that might be responsible for the production of ROS
      after the induction of LTP. Finally, we propose a functional ROS continuum to
      help explain this dichotomy of ROS function in hippocampal LTP.

PMID- 12237860
TI  - Myelin proteolipid protein, basic protein, the small isoform of myelin-associated
      glycoprotein, and p42MAPK are associated in the Triton X-100 extract of central
      nervous system myelin.
AB  - To further our understanding of the functions of the major myelin proteins,
      myelin basic protein (MBP) and proteolipid protein (PLP), and other myelin
      proteins, such as 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and myelin
      associated glycoprotein (MAG), bovine brain myelin was extracted with Triton X
      100, and protein complexes in the detergent-soluble fraction were isolated by
      coimmunoprecipitation and sucrose density gradient sedimentation. MBP, PLP, and
      the small isoform of MAG (S-MAG) were coimmunoprecipitated from the detergent
      soluble fraction by anti-PLP, anti-MBP or anti-MAG monoclonal antibodies.
      Additionally, a 30 kDa phosphoserine-containing protein and two phosphotyrosine
      containing proteins (M(r) 30 and 42 kDa) were found in the coimmunoprecipitates.
      The 42 kDa protein is probably p42MAPK, in that MAPK was shown also to be present
      in the immunoprecipitated complex. CNP, the small PLP isoform DM20, the large MAG
      isoform L-MAG, MOG, CD44, MEK, p44MAPK, and actin were not present in the
      immunoprecipitates, although they were present in the detergent-soluble fraction.
      Lipid analysis revealed that the PLP-MBP-S-MAG coimmunoprecipitated with some
      phospholipids and sulfatide but not cholesterol or galactosylceramide. However,
      the complex had a high density, indicating that the lipid/protein ratio is low,
      and it was retained on a Sepharose CL6B column, indicating that it is not a large
      membrane fragment. Given that MAG is localized mainly in the periaxonal region of
      myelin, where it interacts with axonal ligands, the PLP-MBP-S-MAG complex may
      come from these regions, where it could participate in dynamic functions in the
      myelin sheath and myelin-axonal interactions.

PMID- 12237861
TI  - Protein tyrosine phosphatase sigma-deficient mice show aberrant cytoarchitecture
      and structural abnormalities in the central nervous system.
AB  - Protein tyrosine phosphatase sigma (PTPsigma) is a member of the LAR family of
      receptor tyrosine phosphatases and is highly expressed in the nervous system
      during development. PTPsigma is homologous to the Drosophila DLAR, which plays a
      key role in the targeting of axonal growth cones in flies. We have previously
      inactivated the Ptprs gene in mice and demonstrated stunted growth, developmental
      delays, and neurological and neuroendocrine defects in the PTPsigma null animals.
      Here, we mapped the expression of the lac-Z reporter gene included in the
      knockout cassette and surveyed the development of the CNS in these mice after
      birth. The strongest expression of beta-galactosidase (PTPsigma) was observed in
      the hippocampus, cerebral cortex, olfactory bulbs, and subependymal layer. Our
      analysis reveals hippocampal dysgenesis, reductions in the thickness of the
      corpus callosum and the cerebral cortex, and late expression of the growth
      associated protein 43 (GAP-43) in the knockout animals. Architectural
      abnormalities in the brain and spinal cord were confirmed by immunoreactivity to
      neurofilament and glial fibrillary acidic protein (GFAP) antibodies. Several of
      these neural abnormalities were corrected with age, suggesting a delay in
      neurological development related to the knockout of the Ptprs gene. These data
      suggest that PTPsigma is likely involved in neurogenesis, axonal growth, and
      axonal pathfinding in the maturation of the mammalian CNS.

PMID- 12237862
TI  - Inhibition of insulin-like growth factor I activity contributes to the premature
      apoptosis of cerebellar granule neuron in weaver mutant mice: in vitro analysis.
AB  - Evidence from transgenic mice and cultured cerebellar neurons supports an
      important role for insulin-like growth factor I (IGF-I) in the formation of
      cerebellar cytoarchitecture. To understand IGF-I's function during cerebellar
      development, we examined the involvement of IGF-I in the premature apoptosis of
      granule neurons derived from the cerebella of weaver (wv) mutant mice. Before
      their demise, wv granule neurons increased the expression and secretion of IGFBP5
      in a gene dose-dependent manner. Because IGFBP5 may interfere with the
      interaction of IGF-I and its receptor, the abnormally high IGFBP5 levels in wv
      granule neurons suggest that a lack of IGF-I activation may contribute to their
      premature apoptosis. This hypothesis is supported by a gene dose-dependent
      decrease in IGF-I receptor (IGF-IR) phosphorylation. More importantly, there is a
      parallel gene dose-dependent decrease in Akt activity, which was inversely
      correlated with the activity levels of caspase 3. On the other hand, adding
      IGFBP5 antibody into culture media increased the survival of wv granule neurons,
      whereas adding IGFBP5 decreased the survival of wild-type granule neurons. To
      delineate the interaction between IGF-I and IGFBP5 on wv granule neurons, we
      examined neuronal survival after treating with IGF-I, des(1-3) IGF-I, or IGFBP5
      antibody. At the same concentration, des(1-3) IGF-I was more effective than IGF-I
      in promoting survival, in increasing Akt activity, and in decreasing caspase 3
      activity. These results indicate that IGF-I's actions on wv granule neurons are
      normally inhibited by excess IGFBP5, and sufficient IGF-I receptor activation
      rescues wv granule neurons via stimulating the Akt signaling pathway.

PMID- 12237863
TI  - Chondroitin and keratan sulfates have opposing effects on attachment and
      outgrowth of ventral mesencephalic explants in culture.
AB  - During rat brain development, striatal proteoglycan (PG) expression shows
      specific spatio-temporal modifications suggesting a possible role in the guidance
      of its dopaminergic afferents. The effects of individual glycosaminoglycans
      (GAGs) on dopaminergic (DA) neuronal adhesion and outgrowth were therefore
      studied. We tested the behavior of dissociated embryonic rat mesencephalic cells
      cultivated on substrate-bound GAGs. Neuronal attachment was very limited and
      quantitative morphometry revealed variations in DA fiber outgrowth depending on
      the type and the concentration of GAG used. Next, we developed a cryoculture
      system to examine how neurons react toward GAGs expressed in situ. Rat brain
      slices from different developmental stages were used as substrates for embryonic
      mesencephalic explants. Preferential regions of adherence and outgrowth were
      observed: the striatum was found to be the most permissive, whereas the cortex
      was inhibitory. Western blotting experiments confirmed quantitative and
      qualitative changes in chondroitin sulfate (neurocan, phosphacan) and keratan
      sulfate (KS) containing PGs in these substrates and enzymatic digestion of GAGs
      before cryoculture revealed a substantial involvement of PGs in DA neuron
      adhesion and outgrowth. In particular, CSPGs seemed to mediate the permissive
      effect of the striatum, whereas KS confers an inhibitory effect to the cortex.
      PGs may thus be important for limiting midbrain projections to the striatum
      during development and for maintaining topography in the adult.

PMID- 12237864
TI  - Low-density lipoprotein receptor-related protein mediates in PC12 cell cultures
      the inhibition of nerve growth factor-promoted neurite outgrowth by pregnancy
      zone protein and alpha2-macroglobulin.
AB  - Human pregnancy zone protein (PZP) is a major pregnancy-associated plasma protein
      closely related to human alpha(2)-macroglobulin (alpha(2)M). It has been
      demonstrated that monoamine-activated forms of human and rat alpha(2)M and rat
      alpha(1)M can bind to TrkA and, respectively, inhibit and stimulate NGF-promoted
      neurite outgrowth, Trk phosphorylation, and intracellular signal transduction in
      PC12 cells. However, the effect of PZP on neurons is unknown, and the molecular
      mechanism of neuroinhibition by monoamine-activated alpha(2)M is still unclear.
      In this report, we show that methylamine-activated PZP (MA-PZP), like MA
      alpha(2)M, inhibits in a dose-dependent way the NGF-promoted neurite extension
      and TrkA phosphorylation in PC12 cells. On the other hand, normal PZP (N-PZP) had
      little or no effect. In addition, the inhibitory effect of activated alpha
      macroglobulins (alphaMs) was reversible upon its removal from the cell culture.
      In addition, PZP, as well as alpha(2)M, is neuroinhibitory without being directly
      cytotoxic. It is known that the activated alphaMs bind to the multiligand
      receptor termed low-density lipoprotein receptor-related protein (LRP) and that
      the receptor-associated protein (RAP) specifically blocks uptake of all known LRP
      ligands. To investigate the potential role of LRP in neuromodulation by activated
      PZP/alpha(2)M, the effect of RAP on the neuroinhibitory activities of these
      alphaMs was also studied. Data presented here show that RAP blocked the neurite-
      and Trk-inhibitory activities of both MA-PZP and MA-alpha(2)M, whereas RAP itself
      had no neuromodulatory effect. Hence, we conclude that these data suggest that
      the LRP receptor and its alphaM ligands may play a role in regulating Trk
      receptors.

PMID- 12237865
TI  - Functional reconnections established by central respiratory neurons regenerating
      axons into a nerve graft bridging the respiratory centers to the cervical spinal
      cord.
AB  - The present work investigated, in adult rats, the long-term functional properties
      and terminal reconnections of central respiratory neurons regenerating axons
      within a peripheral nerve autograft bridging two separated central structures. A
      nerve graft was first inserted into the left medulla oblongata, in which the
      respiratory centers are located. Three months later, a C3 left hemisection was
      performed, and the distal tip of the graft was implanted into the C4 left spinal
      cord at the level of the phrenic nucleus, a natural central inspiratory target.
      Six to eight months after medullary implantation, the animals (n = 12) were
      electrophysiologically investigated to test 1) the phrenic target reinnervation
      by analyzing the phrenic responses elicited by bridge electrical stimulation and
      2) the bridge innervation by unitary recordings of the spontaneous activity of
      regenerated axons within the nerve bridge. In the control group (n = 6), the
      medullary site of implantation corresponded to the dorsolateral medulla, a region
      known to be an unsuitable site for inducing respiratory axonal regrowth after
      nerve grafting. Stimulation of the nerve bridge never elicited phrenic nerve
      response, and no respiratory units were found within the nerve bridge. In the
      experimental group (n = 6), the proximal tip of the nerve bridge was implanted
      within the ventrolateral medulla at the level of the respiratory centers.
      Electrical stimulation of the nerve bridge induced phrenic nerve responses that
      reflected a postsynaptic activation of the phrenic target. Subsequent unitary
      recordings from teased fibers within the bridge revealed the presence of
      regenerated inspiratory fibers exhibiting discharge patterns typical of medullary
      inspiratory neurons, which normally make synaptic contacts with the inspiratory
      phrenic target. These results indicate that, when provided with an appropriate
      denervated target, central respiratory neurons with regenerated axons along a
      nerve bridge can remain functional for a long period and can make precise and
      specific functional reconnections with central homotypic target neurons.

PMID- 12237866
TI  - Methamphetamine activates DNA binding of specific redox-responsive transcription
      factors in mouse brain.
AB  - Cellular oxidative stress and alterations in redox status can be implicated in
      methamphetamine (METH)-induced neurotoxicity. To elucidate the molecular
      signaling pathways of METH-induced neurotoxicity, we investigated the effects of
      a single intraperitoneal injection of METH (1.0, 10, or 20 mg/kg) on DNA-binding
      activity of specific redox-sensitive transcription factors in mouse brain.
      Transcription factors studied included activator protein-1 (AP-1), nuclear factor
      kappaB (NF-kappaB), cAMP-responsive element-binding protein (CREB), SP-1, and
      signal transducers and activators of transcription (STAT1 and STAT3). Significant
      and dose-dependent inductions of AP-1 and CREB DNA-binding activities were
      observed in four different regions (striatum, frontal cortex, hippocampus, and
      cerebellum) isolated from the brains of mice injected with METH. However,
      injections with METH did not affect DNA binding activities of NF-kappaB, SP-1,
      STAT1, and STAT3. These results suggest that METH-induced oxidative stress may
      trigger the molecular signaling pathways via specific and selective activation of
      AP-1 and CREB.

PMID- 12237867
TI  - Neuroprotective effect of estradiol and phytoestrogens on MPP+-induced
      cytotoxicity in neuronal PC12 cells.
AB  - A large body of experimental evidence supports a role for oxidative stress as a
      mediator of nerve cell death in Parkinson's disease. To better understand the
      cellular insult of oxidative stress on dopaminergic neurons, we studied the
      cytotoxic effect of the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      metabolite, 1-methyl-4-phenyl pyridium (MPP(+)), on several parameters of cell
      distress using neuronal PC12 cells. We also measured the level of protein
      expression for the dopamine transporter and the estrogen receptors alpha and
      beta. Since estrogens have been reported to prevent neuronal degeneration caused
      by increased oxidative burden, we investigated the ability of 17beta-estradiol,
      the stereoisomer 17alpha-estradiol, and several phytoestrogens to rescue neuronal
      PC12 cells submitted to MPP(+)-induced cytotoxicity. Our results consistently
      show a protective effect of 17alpha-estradiol, 17beta-estradiol and certain
      phytoestrogens such as quercetin and resveratrol, in neuronal PC12 cells treated
      with MPP(+). In our cellular paradigm, phytoestrogens coumestrol, genistein, and
      kaempferol did not revert MPP(+)-induced cellular death. By Western blot, we
      demonstrated that administration of MPP(+) alone decrease dopamine transporter
      expression, while treatments with MPP(+) together with 17alpha-estradiol, 17beta
      estradiol, quercetin, or resveratrol could restore dopamine transporter protein
      expression to control levels. Moreover, the same treatments did not modulate
      alpha estrogen receptor or beta estrogen receptor expression. By these studies,
      we aim to provide more evidence for the involvement of phytoestrogens in the
      process of neuroprotection and to test our hypothesis that some of these
      compounds may act as neuroprotective molecules and have a lesser hormonal effect
      than estrogens.

PMID- 12237868
TI  - Neuroprotective effects of prostaglandin E2 or cAMP against microglial and
      neuronal free radical mediated toxicity associated with inflammation.
AB  - Prostaglandin E(2) (PGE(2)), a product of the cyclooxygenation of arachidonic
      acid released from membrane phospholipids, plays a critical role in inflammatory
      neurodegenerative conditions. Despite its classic role as a proinflammatory
      molecule, exogenous PGE(2) was suggested to have protective roles against
      neuronal death, although the exact protective mechanisms of PGE(2) are not yet
      defined. Thus, the aim of this study was to examine the effect of exogenous
      PGE(2) on inflammatory neurotoxicity. Lipopolysaccharide (LPS) induced neuronal
      toxicity, which was associated with terminal transferase dUTP nick end labeling
      (TUNEL)-positive neuronal death with increased caspase-3 activity. In neuron
      glial coculture, LPS markedly induced inducible nitric oxide synthase/nitric
      oxide (iNOS/NO) release from microglial cells, but not from neurons; however, LPS
      induced oxidative stress such as reactive oxygen species (ROS), measured with 2,7
      dichlorofluorescein diacetate oxidation, was increased in neurons, but not in
      microglial cells. Exogenous PGE(2) (1 microg/ml) rescued the neurons, reducing
      iNOS/NO release from microglial cells and ROS formation from neurons. PGE(2) has
      been known to increase intracelluar cyclic adenosine monophosphate (cAMP) levels.
      In this study, we found that intracellular cAMP elevating agents, forskolin, and
      cAMP analogue, dbcAMP and 8-Br-cAMP, also prevented LPS-induced neuronal death.
      Thus, these results indicate that exogenous PGE(2) protects against LPS-induced
      neuronal apoptotic cell death through the intracellular cAMP system, and is
      associated with the modulation of NO from microglial cells and ROS production
      from neurons.

PMID- 12237869
TI  - Maturation-dependent neurotoxicity of lead acetate in vitro: implication of glial
      reactions.
AB  - Despite a wealth of data on the neurotoxic effects of lead at the cellular and
      molecular levels, the reasons for its development-dependent neurotoxicity are
      still unclear. Here, the maturation-dependent effects of lead acetate were
      analyzed in immature and differentiated brain cells cultured in aggregates.
      Markers of general cytotoxicity as well as cell-type-specific markers of glial
      and neuronal cells showed that immature brain cells were more sensitive to lead
      than the differentiated counterparts, demonstrating that the development
      dependent neurotoxicity of lead can be reproduced in aggregating brain cell
      cultures. After 10 days of treatment, astrocytes were found to be more affected
      by lead acetate than neurons in immature cultures, and microglial cells were
      strongly activated. Eleven days after cessation of the treatment, lead acetate
      caused a partial loss of astrocytes and an intense reactivity of the remaining
      ones. Furthermore, microglial cells expressed a macrophagic phenotype, and the
      loss of activity of neuron-specific enzymes was aggravated. In differentiated
      cultures, no reactive gliosis was found. It is hypothetized that the intense
      glial reactions (microgliosis and astrogliosis) observed in immature cultures
      contribute to the development-dependent neurotoxicity of lead.

PMID- 12237870
TI  - Glutamate-dependent transcriptional regulation of the chkbp gene: signaling
      mechanisms.
AB  - Glutamate, the major excitatory neurotransmitter, induces a signal from the
      membrane to the nucleus that regulates gene expression. The gene encoding the
      chick kainate binding protein undergoes a glutamate-dependent transcriptional
      regulation via an activator protein-1 site within its promoter region. To
      characterize this event, cultured chick Bergmann glia cells were exposed to
      glutamate, and a dose-dependent increase in promoter activity was established.
      The glutamate effect is mediated through Ca(2+)-permeable alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid/kainate receptors. The signaling cascade
      includes phosphatidyl inositol 3-kinase, Ca(2+)/calmodulin-dependent protein
      kinase II, mitogen-activated protein kinase, and p90 ribosomal S6 kinase
      activation. The cAMP response-element binding protein becomes phosphorylated and
      activates fos transcription. Finally, the activator protein-1 complex binds to
      the glutamate response element in the chick kainate binding protein promoter
      region inducing its activity. We propose that the mitogen-activated protein
      kinase/p90 ribosomal S6 kinase pathway plays a critical role in glutamate-induced
      gene transcription.

PMID- 12237872
TI  - E2F1 selects tumour cells for both life and death.
AB  - E2F1 is a transcription factor involved in both cell cycle progression and
      apoptosis. Perhaps surprisingly, these two processes are closely related, and the
      choice between them appears to be made on the basis of the aggregate of signals
      flowing into the cell at the time. This may be the means whereby normal cells
      tune their threshold for apoptosis with respect to the availability of external
      growth factors, so that cells that are supernumerary to the tissue's needs at the
      time can be immediately deleted. In many tumours, however, the pathways that link
      E2F1 activity to apoptosis have been interrupted, sometimes at multiple points.
      Non-small-cell lung carcinoma provides a striking example of this, with the
      result that expression of E2F1 in these tumours does not correlate with apoptosis
      but is a good surrogate marker for replicative status. This relationship does not
      necessarily pertain in other tumour types. Molecules such as E2F1 lie at the core
      of very significant cell fate decisions, but they are part of a complex matrix of
      interactions, all of which must be surveyed before interpretation in terms of
      tumour behaviour is possible. Microarray analysis may provide a way to do this.
      In the future, however, such interpretations, including predictions of
      therapeutic response, may be possible through interrogation of the status of a
      relatively limited number of molecules. Those that preside over critical cellular
      decision forks (such as the choice between proliferation or death) are good
      candidates for this role. E2F1 clearly qualifies as one member of this group.

PMID- 12237873
TI  - Transcription factor E2F-1 acts as a growth-promoting factor and is associated
      with adverse prognosis in non-small cell lung carcinomas.
AB  - Numerous upstream stimulatory and inhibitory signals converge to the pRb/E2F
      pathway, which governs cell-cycle progression, but the information concerning
      alterations of E2F-1 in primary malignancies is very limited. Several in vitro
      studies report that E2F-1 can act either as an oncoprotein or as a tumour
      suppressor protein. In view of this dichotomy in its functions and its critical
      role in cell cycle control, this study examined the following four aspects of E2F
      1 in a panel of 87 non-small cell lung carcinomas (NSCLCs), previously analysed
      for defects in the pRb-p53-MDM2 network: firstly, the status of E2F-1 at the
      protein, mRNA and DNA levels; secondly, its relationship with the kinetic
      parameters and genomic instability of the tumours; thirdly, its association with
      the status of its transcriptional co-activator CBP, downstream target PCNA and
      main cell cycle regulatory and E2F-1-interacting molecules pRb, p53 and MDM2; and
      fourthly, its impact on clinical outcome. The protein levels of E2F-1 and its co
      activator CBP were significantly higher in the tumour area than in the
      corresponding normal epithelium (p<0.001). E2F-1 overexpression was associated
      with increased E2F-1 mRNA levels in 82% of the cases examined. The latter
      finding, along with the low frequency of E2F-1 gene amplification observed (9%),
      suggests that the main mechanism of E2F-1 protein overexpression in NSCLCs is
      deregulation at the transcriptional level. Mutational analysis revealed only one
      sample with asomatic mutation at codon 371 (Glu-->Asp) and one carrying a
      polymorphism at codon 393 (Gly-->Ser). Carcinomas with increased E2F-1 positivity
      demonstrated a significant increase in their growth indexes (r=0.402, p=0.001)
      and were associated with adverse prognosis (p=0.033 by Cox regression analysis).
      The main determinant of the positive association with growth was the parallel
      increase between E2F-1 staining and proliferation (r=0.746, p<0.001), whereas
      apoptosis was not influenced by the status of E2F-1. Moreover, correlation with
      the status of the pRb-p53-MDM2 network showed that the cases with aberrant pRb
      expression displayed significantly higher E2F-1 indexes (p=0.033), while a
      similar association was noticed in the group of carcinomas with deregulation of
      the p53-MDM2 feedback loop. In conclusion, the results suggest that E2F-1
      overexpression may contribute to the development of NSCLCs by promoting
      proliferation and provide evidence that this role is further enhanced in a
      genetic background with deregulated pRb-p53-MDM2 circuitry.

PMID- 12237874
TI  - Immunohistochemical expression of cyclin D1, E2F-1, and Ki-67 in benign and
      malignant thyroid lesions.
AB  - Cyclin D1 and E2F-1 proteins are essential for the regulation of the G1/S
      transition through the cell cycle. Cyclin D1, a product of the bcl-1 gene,
      phosphorylates the retinoblastoma protein, releasing E2F-1, which in turn
      activates genes involved in DNA synthesis. Expression patterns of E2F-1 protein
      in thyroid proliferations have not been reported. This study used monoclonal
      antibodies for cyclin D1 and E2F-1 proteins to immunostain sections of normal
      thyroid, hyperplastic (cellular) nodules, follicular adenomas, follicular
      carcinomas, and papillary carcinomas. The proliferation rate was examined using
      an antibody specific for the Ki-67 antigen. Fluorescence in situ hybridization
      (FISH) methods and chromosome 11-specific probes were also employed to determine
      chromosome copy number and to assess for evidence of amplification at the 11q13
      locus in papillary and follicular carcinomas with cyclin D1 overexpression.
      Concurrent overexpression of Ki-67, cyclin D1, and E2F-1 was found in the
      majority of benign and malignant thyroid lesions, compared with normal thyroid
      tissue. Cyclin D1 up-regulation was not due to extra copies of chromosome 11, or
      bcl-1 gene amplification. Malignant tumours showed the highest expression for all
      three markers, particularly papillary carcinomas. E2F-1 was detected at the same
      or slightly lower levels than cyclin D1. It was only found when cyclin D1 was
      overexpressed. Because cyclin D1 normally activates E2F-1, up-regulation of
      cyclin D1 may lead to E2F-1 overexpression in benign and malignant thyroid
      lesions.

PMID- 12237875
TI  - Detection of three common translocation breakpoints in non-Hodgkin's lymphomas by
      fluorescence in situ hybridization on routine paraffin-embedded tissue sections.
AB  - Non-random chromosomal translocations are specifically involved in the
      pathogenesis of many non-Hodgkin's lymphomas and have clinical implications as
      diagnostic and/or prognostic markers. Their detection is often impaired by
      technical problems, including the distribution of the breakpoints over large
      genomic areas. This study reports a fluorescence in situ hybridization (FISH)
      method which allows the detection of specific chromosomal breakpoints in tissue
      sections from routinely fixed, paraffin-embedded samples. Hybridization was
      performed after demasking the DNA. Previously validated locus-specific probes
      (cosmids, PACs) flanking the BCL1, BCL2 regions and similar new probes for the
      MYC breakpoint region were used. The cases studied were five mantle cell
      lymphomas (MCL) and five follicular lymphomas (FL), selected on the basis of a
      previously proved t(11;14) and t(14;18) and five randomly chosen Burkitt's
      lymphomas (BL), as well as 21 negative control samples. In all samples,
      hybridization signals of sufficient intensity were obtained. Three different
      algorithms were used to score the hybridization signals in tissue sections, two
      of them taking into account the nuclei and their signal distribution indicative
      of chromosomal break, and one only considering the colocalization or segregation
      of the signals. In control tissues, these algorithms resulted in cut-off levels
      of 9.1%, 1.3%, or 10.0%. In the 15 lymphoma samples the percentages of abnormal
      cells/signals ranged from 28% to 80%, 13% to 49%, and 40% to 70%, respectively.
      The results indicate that small locus-specific probes can be used in FISH for
      regular detection of translocation breakpoints on routine paraffin tissue
      sections.

PMID- 12237876
TI  - Combined analysis of T cell receptor gamma and immunoglobulin heavy chain gene
      rearrangements at the single-cell level in lymphomas with dual genotype.
AB  - By prospectively studying immunoglobulin heavy chain gene (IgH) and T cell
      receptor gamma (TCRgamma) gene rearrangements in 398 lymphoma cases, a dual
      genotype was observed in 13% of B cell and 11% of T cell lymphomas. According to
      histological subtype, the highest incidence was observed for mantle cell
      lymphomas (32%) and lymphoplasmacytic lymphoma (21%) among B cell lymphomas, and
      for angioimmunoblastic lymphoma (AILT) (46%) and Sezary syndrome (SS) (50%) among
      T cell lymphomas. To determine whether the dual genotype corresponds to the
      presence of two distinct monoclonal populations or to the presence of both
      rearrangements within the same lymphoma cells, single-cell microdissection was
      used after immunohistochemistry and a single-cell combined IgH and TCRgamma gene
      analysis was designed after a whole-genome amplification step. This protocol was
      applied to the study of two nodal B cell lymphomas (one diffuse large B cell
      lymphoma and one mantle cell lymphoma) and two cutaneous T cell lymphomas (one
      AILT and one SS). Two cases (SS and mantle cell lymphoma) were true bigenotypic
      lymphomas, as both IgH and TCRgamma monoclonal rearrangements were detected in
      the same cells. Conversely, in the diffuse large B cell lymphoma and AILT cases,
      large CD22+ single cells exhibited only the monoclonal IgH rearrangement but not
      the TCRgamma gene that was detected in CD3+ single cells. Such an approach allows
      the identification of true bigenotypic lymphoma among dual genotypic lymphoma.
      Specific genetic alterations may be further amplified from microdissected
      cryopreserved material, such as the t(11;14) breakpoint detected in bigenotypic B
      cells of the mantle cell lymphoma case.

PMID- 12237877
TI  - Telomerase as a prognostic marker in breast cancer: high-throughput tissue
      microarray analysis of hTERT and hTR.
AB  - Telomerase activity (TA) has been shown to correlate with poor clinical outcome
      in various tumour entities, indicating that tumours expressing this enzyme may be
      more aggressive and that TA may be a useful prognostic marker. For breast cancer,
      however, TA is a controversial prognostic marker; whereas some studies suggest an
      association between TA and disease outcome, others do not find this association.
      This study used tissue microarrays (breast carcinoma prognosis arrays) containing
      611 samples (each 0.6 mm in diameter) from the tumour centre of paraffin-embedded
      breast carcinomas to analyse the catalytic subunit of telomerase, human
      telomerase reverse-transcriptase (hTERT), and the internal RNA component (hTR),
      which are the core components of the telomerase holoenzyme complex. hTERT protein
      expression was obtained by immunohistochemistry (human anti-telomerase antibody
      Ab-2, Calbiochem), and hTR RNA was measured by radioactive in situ hybridization.
      hTERT and hTR expression were determined semi-quantitatively and graded (scores 1
      4). Clinical data, such as histological subtype, pT stage, tumour diameter, pN
      stage, BRE grade, tumour-specific survival (in months), patient's age and others,
      were available for statistical analysis. A statistically significant correlation
      was found between tumour-specific survival (overall survival) and hTERT
      expression (p < 0.0001) or hTR expression (p = 0.00110). Tumours with higher
      scores (scores 3, 4) for hTR and/or hTERT were associated with a worse prognosis.
      In multivariate analysis, hTERT expression was an independent prognostic factor.
      Previous studies, focusing on analysis of TA in smaller numbers of fresh-frozen
      breast carcinomas by the TRAP assay, gave controversial results with respect to
      TA as a prognostic marker. Using tissue microarrays from 611 breast carcinomas,
      this study has demonstrated that increased expression levels of the telomerase
      core components, hTERT and hTR, are associated with lower overall survival. These
      findings suggest that TA should be included in future validation studies as a
      prognostic marker in breast cancer.

PMID- 12237878
TI  - Microsatellite analysis of breast carcinoma and corresponding local recurrences.
AB  - Local recurrence is a serious complication of breast carcinoma that reduces
      quality of life and influences prognosis. The aim of this study was to determine
      whether local recurrences of breast carcinoma are genetically related to the
      primary tumours. Forty cases of locally recurrent breast carcinomas (median
      onset: 3.6 years after primary surgery) were analysed: 22 patients had undergone
      breast-conserving therapy and 18 mastectomy. Eighteen microsatellites on
      chromosomes 2p, 3p, 5q, 10q, 11p, 11q, 13q, 17q, 17p, 18p were amplified by PCR
      using fluorescent-labelled primers, automatically detected after polyacrylamide
      gel electrophoresis and analysed for loss of heterozygosity (LOH) or
      microsatellite instability (MSI). Follow-up data were available for 39 cases with
      a median value of 89 months. All LOH and MSI found in the primary tumours were
      also present in the corresponding recurrences, indicating that they are
      genetically related to the primary tumours and not secondary malignancies in the
      same breast. MSI was found in three cases, of which one harboured MSI at more
      than two loci. The median value of LOH per case was significantly higher in the
      recurrent (four per case) compared to the primary tumours (two per case; p <
      0.001, Mann-Whitney test), reflecting the genotype of tumour progression. Early
      local recurrence was associated with specific LOH for TP53.15 (p = 0.018, log
      rank test) in the primary tumours. LOH on D13S1699 or D17S855 was associated with
      lymph node metastases (p = 0.024 and p = 0.019, respectively; chi-square test).
      In addition, tumour grade, lack of oestrogen or progesterone receptor expression,
      young patient age and early appearance of local recurrence significantly
      correlated with poor survival. The development of local recurrence despite clear
      resection margins may result from residual DCIS distant from the invasive
      carcinoma, homing of circulating tumour cells, or genetically altered,
      histologically normal breast tissue not immediately adjacent to the invasive
      carcinoma.

PMID- 12237879
TI  - Quantification of CK20 gene and protein expression in colorectal cancer by RT-PCR
      and immunohistochemistry reveals inter- and intratumour heterogeneity.
AB  - Cytokeratin 20 (CK20) is an epithelial protein expressed almost exclusively in
      the gastrointestinal (GI) tract and is widely used as immunohistochemical marker
      for routine diagnosis. In contrast, CK20 gene expression is not an established
      marker for the classification of tumours and the detection of disseminated cancer
      cells in colorectal cancer. Recently, real-time reverse transcriptase polymerase
      chain reaction (RT-PCR) has provided the means for reproducible and quantitative
      investigation of molecular markers. This report directly compares CK20 mRNA and
      protein expression in serial sections of archival, formalin-fixed, paraffin
      embedded (FFPE) colorectal adenocarcinomas. CK20 expression was detected by
      immunohistochemistry (IHC) in 60/63 (95.2%) cases, by conventional RT-PCR in
      58/60 (96.7%) and by quantitative RT-PCR using the LightCycler (LightCycler is a
      trademark of a Member of the Roche Group) System in 29/32 (90.6%) microdissected
      cases, one case yielding variable results. Despite the high detection rate of all
      three techniques, marked heterogeneity of CK20 expression was seen between
      different cases and also within individual cases. CK20 expression profiles were
      not related to particular histopathological features of the tumours. A good
      correlation (r = 0.8964) was found between CK20 mRNA and protein expression by
      comparing quantitative RT-PCR with IHC in 32 cases. This was also true for
      selected heterogeneous tumour cells within individual cases. Both RT-PCR and IHC
      are therefore valuable tools for CK20 detection in colorectal adenocarcinoma,
      with real-time RT-PCR providing supplementary quantitative information. This
      suggests a promising supportive role for quantitative RT-PCR in molecular
      pathology.

PMID- 12237880
TI  - Polarized distribution of carcinoembryonic antigen is associated with a tight
      junction molecule in human colorectal adenocarcinoma.
AB  - This study we presents a novel anti-occludin monoclonal antibody that can be used
      for formalin-fixed, paraffin-embedded tissue sections. The relationships between
      aberrant localization of carcinoembryonic antigen (CEA) and abnormalities of
      tight junctions were studied in human colorectal cancers by this antibody.
      Abnormalities in the cell surface expression of CEA have been shown to be
      characteristic of human colorectal cancer cells. Cancer cells that participated
      in the formation of glandular structures expressed occludin at the apical cell
      border and CEA was expressed more apically than occludin. Where cancer cells
      showed solid nests without glandular structures, occludin was completely lost and
      CEA was demonstrated in a diffuse pattern throughout the cells. These findings
      suggest that the polarized apical expression of CEA in neoplastic glandular
      structures depends on the expression of occludin and the fence function of tight
      junctions. During tumour progression, loss of occludin may lead to the loss of
      membrane polarity and the non-polarized expression of CEA. The antibody described
      provides a powerful tool for the study of tight junctions in surgically resected
      human tissue.

PMID- 12237881
TI  - Frequent expression of the multi-drug resistance-associated protein
      BCRP/MXR/ABCP/ABCG2 in human tumours detected by the BXP-21 monoclonal antibody
      in paraffin-embedded material.
AB  - Breast cancer resistance protein (BCRP/MXR/ABCP/ABCG2; hereafter ABCG2) is a
      member of the ATP-binding-cassette family of transporters that causes multi-drug
      resistance to various anticancer drugs. The expression of ABCG2 in human tumours
      and its potential involvement in clinical drug resistance are unknown. Recently,
      two monoclonal antibodies against human ABCG2 were produced, BXP-34 and BXP-21.
      This study describes an immunohistochemical method using BXP-21 to study ABCG2
      expression in formalin-fixed, paraffin-embedded tissues. No staining was seen
      using BXP-34 with the same protocols. The expression of ABCG2 was then
      investigated in a panel of 150 untreated human solid tumours comprising 21 tumour
      types. Overall, ABCG2 expression was frequent. Specificity of
      immunohistochemistry was confirmed by the detection of a 72 kD band in western
      blotting. ABCG2 expression was seen in all tumour types, but it seemed more
      frequent in adenocarcinomas of the digestive tract, endometrium, and lung, and
      melanoma. Positive tumours showed membranous and cytoplasmic staining. In certain
      adenocarcinomas, prominent membranous staining was seen. Endothelial cells
      frequently displayed moderate to strong staining. ABCG2 is widely present in
      untreated human solid tumours and may represent a clinically relevant mechanism
      of drug resistance. Future studies in specific tumour types are needed to
      ascertain its clinical relevance. BXP-21 and the immunohistochemical protocol
      described here will be of value in these investigations.

PMID- 12237882
TI  - Proinflammatory cytokine (TNFalpha/IL-1alpha) induction of human osteoclast
      formation.
AB  - TNFalpha and IL-1alpha are potent stimulators of bone resorption in vivo and in
      vitro. Recently, it has been demonstrated that these two cytokines directly
      induce osteoclastogenesis in mouse marrow cultures. This study determined whether
      TNFalpha (+/- IL-1alpha) is also capable of inducing human osteoclastogenesis.
      The CD14(+) monocyte fraction of human peripheral mononuclear cells was cultured
      with TNFalpha +/- IL-1alpha in the presence of M-CSF. TNFalpha induced the
      formation of multinucleated cells (MNCs) which were positive for TRAP, VNR and
      cathepsin K and showed evidence of resorption pit formation. IL-1alpha stimulated
      TNFalpha-induced lacunar resorption two- to four-fold. Osteoprotegerin, the decoy
      receptor for RANKL, did not inhibit this process. Anti-human IL-1alpha
      neutralizing antibodies significantly inhibited resorption without inhibiting the
      formation of TRAP(+)/VNR(+) MNCs. These results suggest that, in the presence of
      M-CSF, TNFalpha is sufficient for inducing human osteoclast differentiation from
      circulating precursors by a process which is distinct from the RANK/RANKL
      signalling pathway.

PMID- 12237883
TI  - RANK ligand is a prerequisite for cancer-associated osteolytic lesions.
AB  - Breast cancer is frequently associated with osteolytic bone metastasis, where
      osteoclasts play a major role in bone destruction. Recently, osteoclast
      differentiation factor (RANKL) has been identified as a prerequisite for the
      formation and maintenance of osteoclasts from haematopoietic precursors. To
      elucidate the mechanism of osteoclastogenesis and bone destruction in bone
      residing breast cancer, PTHrP-producing (MCF-7) and -non-producing (MCF-7UP)
      human breast cancer cells were subcutaneously injected into the forehead of nude
      mice maintained without oestrogen supplement. One, two, and three weeks
      thereafter, the expression of RANKL and PTHrP mRNA, and osteoclastogenesis were
      analysed by in situ hybridization and TRAP staining. In MCF-7 cells, at early
      stages, spindle-shaped stromal cells and osteoblasts on the bone surface
      expressed RANKL, then numerous osteoclasts were induced on the periosteal bone
      surface. Three weeks after the transplantation, MCF-7 cancer cells migrated onto
      the eroded bone surface, where they survived apoptosis. At all stages, RANKL
      expression was confined to the stromal/osteoblastic cells, whereas PTHrP was
      confined to the MCF-7 breast cancer cells. On the other hand, PTHrP was negative
      in MCF-7UP cells at all stages, and neither induction of osteoclasts nor
      infiltrative growth of cancer cells was observed. Moreover, in vitro treatment
      with PTHrP resulted in increased RANKL mRNA expression and transcription activity
      in the MC3T3-E1 mouse osteoblastic cell line. Thus PTHrP induces osteoclastic
      bone resorption through the transactivation of the RANKL gene on
      stromal/osteoblastic cells, affording a bone microenvironment conducive to the
      survival of PTHrP-producing cancer cells.

PMID- 12237884
TI  - Amplification of the androgen receptor gene in bone metastases from hormone
      refractory prostate cancer.
AB  - The aim of this study was to examine the prevalence of androgen receptor (AR)
      amplification in metastases to bone and other sites in patients with hormone
      refractory prostate cancer (HRPC) and to compare these findings with those in
      pretreatment primary tumour samples from the same patients. Tissue from 24
      patients with HRPC was available for study, together with 13 primary tumour
      specimens. AR gene amplification and copy number for X-chromosome were assessed
      by fluorescence in situ hybridization (FISH) using a SpectrumOrange-labelled
      probe at locus Xq11-13 for the AR gene and a SpectrumGreen-labelled alpha
      satellite probe for the X-chromosome (Vysis, UK, Ltd.). A minimum of 20 nuclei
      were scored in each of three tumour areas by two independent observers. Samples
      from 18/24 patients with HRPC (12 bone marrow biopsies, three local tumour
      recurrences, and three lymph nodes) and nine primary tumour specimens were
      adequate for FISH analysis. Results were expressed as a mean ratio of AR gene
      copy number : mean X-chromosome number, with a ratio of greater than 1.5 defined
      as amplification. AR gene amplification was seen in 9/18 (50%) cases of HRPC and
      in none of the primary (untreated) tumour specimens (p = 0.0048, Fisher's exact
      test). For the 12 bone marrow samples, AR gene amplification occurred in 5/12
      (38%) cases. Elevated copy number for chromosome X occurred in 3/18 (17%) HRPC
      and 4/9 (44%) matched primary tumours. This study shows for the first time that
      AR gene amplification can be demonstrated by FISH in bone metastases from HRPC
      patients. Because bone marrow biopsies can be obtained from most patients with
      HRPC, the findings provide a rational basis for the routine selection of patients
      who may respond more favourably to second-line anti-androgen therapy.

PMID- 12237885
TI  - Frequent FGFR3 mutations in urothelial papilloma.
AB  - Activating point mutations in the FGFR3 gene occur frequently in low-grade and
      low-stage bladder carcinomas, whereas they are rare in high-grade carcinomas.
      This study investigates the incidence of FGFR3 mutations in 12 urothelial
      papillomas and 79 pTaG1 tumours which were regraded according to the 1998
      WHO/ISUP classification system, resulting in 62 papillary urothelial neoplasms of
      low malignant potential (PUNs-LMP) and 17 low-grade papillary urothelial
      carcinomas (LG-PUCs). FGFR3 mutation analysis of 21 ovarian Brenner tumours was
      also performed. Seventy-seven cases were detected with a mutation in the FGFR3
      gene. The mutations were exclusively found in bladder neoplasms. In urothelial
      papilloma, generally considered a benign lesion, 9/12 (75%) mutations were found.
      This report is the first to describe a genetic defect in urothelial papilloma. A
      comparable percentage of mutations was found in PUNs-LMP (85%) and LG-PUCs (88%).
      No mutations were found in matched normal DNA from bladder tumour patients. The
      mean follow-up was 5.78 years (range 0.21-17.60 years). Five patients developed
      high-grade papillary urothelial carcinoma from 2.5 to 12 years after first
      diagnosis. Two patients died of bladder cancer. The mean number of recurrences
      (recurrence rate) per year was 0.03, 0.21, and 0.46, respectively, for papilloma,
      PUN-LMP, and LG-PUC. Urothelial papilloma is a rare lesion with a benign natural
      behaviour compared with PUN-LMP and LG-PUC of the bladder, but from a molecular
      perspective, papillomas should be classified together with all well
      differentiated urothelial neoplasms.

PMID- 12237886
TI  - Steroid hormone receptor in pleural solitary fibrous tumours and CD34+ progenitor
      stromal cells.
AB  - Solitary fibrous tumours (SFT), originally described in the pleura, were
      subsequently recognized in numerous extrapleural sites. This suggests that a
      common stem cell, present in various organs and tissues, may be at the origin of
      SFT and that specific factors may be involved in the proliferation of such cells.
      Recently it has been described that steroid hormone receptors, progesterone
      receptors in particular, are expressed by extrapleural SFT. In addition,
      progesterone may participate as growth factor in many CD34(+) stromal neoplasms,
      which express low levels of the hormone receptors. The present study analysed the
      expression of androgen (AR), oestrogen (ER) and progesterone (PR) receptors in a
      series of 32 pleural SFT, 10 mesotheliomas and in reactive tissue of chronic
      pleuritis. ER and AR were never expressed by SFT or by chronic pleuritis, whereas
      PR were demonstrated in 2/16 "large" (>8 cm) and in 6/16 "small" (< or =8 cm)
      pleural SFT (all expressing CD34, bcl-2 and CD99). PR(+) SFT had a significantly
      higher proliferative activity (p = 0.04) (Ki-67 mean value 6.5%) and lower
      p27(kip1) (mean value 51.5%) expression than the PR(-) cases (Ki-67 mean value
      3.81% and p27(kip1) mean value 57.86%). One of the cases expressing a high level
      of PR (80%) recurred 1 year after first surgery and the recurrence was PR(+) as
      well, but with a lower percentage of nuclear receptor expression (12%). In
      addition, in chronically inflamed subserosal tissue, a subpopulation of CD34(+)
      endothelial and interstitial dendritic cells was identified, which also expressed
      PR. These findings suggest that the CD34(+) submesothelial interstitial dendritic
      cells, activated during reactive processes, may be the stem cells that give rise
      to SFT, and that progesterone might participate in the growth of SFT through
      modulation of its specific receptors.

PMID- 12237887
TI  - Metalloelastase (MMP-12) expression by tumour cells in squamous cell carcinoma of
      the vulva correlates with invasiveness, while that by macrophages predicts better
      outcome.
AB  - Human metalloelastase (MMP-12) has been implicated in elastin degradation and
      macrophage migration in many pathological conditions. It also generates
      angiostatin, thus having a potential to prevent tumour angiogenesis. It has
      previously been shown that transformed epithelial cells express MMP-12 in skin
      cancer. The aim of this study was further to elucidate the role of
      metalloelastase in squamous cell cancer (SCC) progression. By in situ
      hybridization, expression of MMP-12 mRNA was detected in 28/33 vulvar SCC samples
      in CD-68-positive macrophages, while 10 samples had positive cancer cells. By
      immunohistochemistry, MMP-12 protein was seen in the same area as the mRNA. MMP
      12 mRNA expression in tumour cells correlated with more aggressive histology (p =
      0.0099). In contrast, macrophage-derived MMP-12 mRNA was more abundant in well
      differentiated grade I than grade III tumours (p = 0.01). However, the level of
      MMP-12 mRNA, regardless of its origin, did not correlate with metastasis or
      patient survival. No significant correlation was found between macrophage-derived
      MMP-12 mRNA and a low amount of blood vessels, as quantitated after von
      Willebrand staining. In agreement with vulvar SCCs in vivo, MMP-12 was expressed
      in cultured SCC cells by northern and western blot analysis. In HaCaTs and
      epithelial MCF-10f cells, MMP-12 mRNA was induced by transforming growth factor
      beta1 (TGF-beta1) and tumour necrosis factor-alpha (TNF-alpha) as measured by
      quantitative RT-PCR (TaqMan). Two MMPs capable of generating angiostatin in vivo,
      matrilysin (MMP-7) and gelatinase B (MMP-9), were also examined in these tumours.
      MMP-7 mRNA was mainly expressed by epithelial tumour cells, particularly in less
      differentiated tumours. MMP-9 was usually expressed by neutrophils and
      macrophages; epithelial protein was predominantly found in grade II/III tumours.
      These results suggest a dual role for MMP-12 in tumour progression.

PMID- 12237888
TI  - Heterogeneous expression of cell adhesion molecules by endothelial cells in ARDS.
AB  - ARDS (acute respiratory distress syndrome) can be associated with septic shock
      and multiple organ failure caused by an uncontrolled systemic inflammatory
      response to Gram-negative bacterial infection. While in animal models the key
      role of the endothelial adhesion molecules ICAM-1, E-selectin, and VCAM in ARDS
      has been extensively studied, there are scarcely any corresponding
      pathomorphological studies of human lung tissue. Hence, little is known about
      whether there is a comparable, or even heterogeneous, expression pattern of these
      molecules in the human pulmonary vasculature. This study was therefore undertaken
      to investigate the immunohistochemical expression of the constitutively expressed
      PECAM (CD31) and the inducible molecules ICAM-1, E-selectin, and VCAM in ARDS
      lungs from patients who had died in septic shock induced by Gram-negative
      bacteria. While in all specimens (ARDS and normal lungs) there was homogeneous
      strong expression of PECAM in all vessels, ICAM-1 was clearly up-regulated in
      ARDS lungs. E-selectin and VCAM were not expressed by endothelial cells (ECs) in
      normal lungs, but in ARDS lungs there was strong expression of both molecules in
      larger vessels, while in the capillaries there was only mosaic-like weak
      expression of a few ECs. This immunohistochemical investigation demonstrates the
      induction and up-regulation of adhesion molecules in human ARDS lungs, comparable
      to that described in animal models. There is also markedly heterogeneous
      expression of E-selectin and VCAM, indicating toporegional differences in the
      function of pulmonary ECs.

PMID- 12237889
TI  - Establishment and characterisation of a human clear cell sarcoma model in nude
      mice.
AB  - We have established a new experimental model of human clear cell sarcoma, UM
      CCS1, using serial subcutaneous transplantation of intact tumour tissue in nude
      mice. The heterotransplanted nude mouse tumours retained characteristic
      morphological features of the primary clear cell sarcoma. Immunohistochemical
      analysis showed the retained expression patterns of S-100 protein, melanoma
      associated antigen HMB-45 and vimentin in the xenografts as compared to the
      primary tumour. DNA index showed low variations both between the xenografts in
      the same passage and between the serial passages. Cytogenetic analysis of the
      primary tumour and the xenografts showed the unbalanced translocation
      der(6)t(6;12)(p23;q13). Based on the combined genetic data a reasonable
      interpretation of our findings is that there was a complex chromosomal
      rearrangement resulting in a cytogenetically cryptic EWS-ATF1 fusion gene.
      Analysis of cell kinetics using in vivo incorporation of iododeoxyuridine and
      flow cytometry showed generally short potential doubling time (T(pot)) of the
      xenografts. Volume doubling time showed low variations without correlation with
      T(pot). The retained phenotypic and genotypic characteristics of the primary
      tumour and the morphological and structural stability over time makes the model
      suitable for studies on the tumour biology and treatment of clear cell sarcoma.

PMID- 12237890
TI  - Upregulation of matrix metalloproteinase-9 in murine 5T33 multiple myeloma cells
      by interaction with bone marrow endothelial cells.
AB  - MM is a B-cell malignancy mainly characterized by monoclonal expansion of plasma
      cells in the BM, presence of paraprotein in serum and occurrence of osteolytic
      bone lesions. MMPs are a family of proteolytic enzymes that can contribute to
      cancer growth, invasion, angiogenesis, bone degradation and other processes
      important in the pathogenesis of MM. We investigated MMP-9 production in the
      5T33MM murine model. Expression of MMP-9 protein in supernatant and cell extracts
      was analyzed by gelatin zymography. The in vitro, stroma-independent variant
      5T33MMvt showed no protein expression of MMP-9 in contrast to in vivo growing MM
      cells, 5T33MMvv. However, when 5T33MMvt cells were injected into naive mice and
      isolated after tumor take (5T33MMvt-vv), they secreted a significant amount of
      MMP-9. These results were confirmed by specific staining of cytospins with an
      anti-MMP-9 antibody. The MMP-9 production by 5T33MMvt-vv cells disappeared when
      the cells were recultured in vitro. These data demonstrated that upregulation of
      MMP-9 occurs in vivo and that this process is dependent on the microenvironment.
      Cocultures of 5T33MMvt cells with STR10 BMECs induced MMP-9 in MM cells, as
      determined by both gelatin zymography and flow-cytometric analysis. In
      conclusion, our results demonstrate that MMP-9 production by MM cells is
      upregulated in vivo by the interaction of MM cells with BMECs.

PMID- 12237891
TI  - High-frequency microsatellite instability predicts better chemosensitivity to
      high-dose 5-fluorouracil plus leucovorin chemotherapy for stage IV sporadic
      colorectal cancer after palliative bowel resection.
AB  - The influence of MSI on treatment outcome of colorectal cancers remains unclear
      and deserves further investigation. We recruited 244 patients with stage IV
      sporadic colorectal cancers for our study, based on appropriate eligibility
      criteria. Patients were nonrandomly allocated to 2 treatment groups of either
      with or without high-dose 5-FU plus leucovorin chemotherapy (HDFL, 5-FU 2,600
      mg/m(2) leucovorin 300 mg/m(2) maximum 500 mg). Each treatment group was further
      divided into 2 subgroups according to high-frequency MSI (MSI-H) status. MSI-H
      was defined as the appearance of MSI in at least 2 of the 5 examined chromosomal
      loci (BAT-25, BAT-26, D5S346, D2S123, D17S250). We compared clinicopathologic
      parameters, p53 overexpression and overall survival between the groups. In
      addition, 4 subgroups were identified as follows: MSI-H(+)HDFL(+), n = 35; MSI-H(
      )HDFL(+), n = 134; MSI-H(+)HDFL(-), n = 17; MSI-H(-)HDFL(-), n = 58. There was no
      significant difference of background clinicopathologic data between the HDFL(+)
      and HDFL(-) treatment groups (p > 0.05). Survival analyses indicated that the
      patients of subgroup MSI-H(+)HDFL(+) survived significantly longer than those of
      subgroup MSI-H(-)HDFL(+), with median survival times of 24 (95% CI 20.2-27.9) and
      13 (95% CI 11.6-14.4) months, respectively (p = 0.0001, log-rank test). In
      contrast, in patients without chemotherapy, the prognosis was poor irrespective
      of MSI status, with median survival times of 7.0 (95% CI 4.6-9.4) and 7.0 (95% CI
      6.1-7.9) months in the MSI-H(+)HDFL(-) and MSI-H(-)HDFL(-) subgroups,
      respectively (p = 0.8205, log-rank test). MSI-H cancers responded significantly
      better to HDFL (p = 0.001), with a mean response rate of 65.71% (95% CI 49.98
      81.44%) in subgroup MSI-H(+)HDFL(+) compared to 35.07% (95% CI 26.99-43.15%) in
      subgroup MSI-H(-)HDFL(+). There appeared to be no preferential metastatic site
      where response to HDFL can be predicted based on the MSI status of the primary
      tumor. Toxicity to HDFL was similarly minimal between MSI-H(+) and MSI-H(-)
      patients (p > 0.05). Multivariate analysis of all patients further indicated that
      MSI-H and chemotherapy were independent favorable prognostic parameters (p <
      0.05). Thus, the better prognosis of stage IV sporadic colorectal cancers with
      MSI-H may be associated with better chemosensitivity, rather than lower
      aggressiveness in biologic behavior.

PMID- 12237892
TI  - Host genetic control of HPV 16 titer in carcinoma in situ of the cervix uteri.
AB  - Cervical cancer is strongly associated with infection by oncogenic forms of human
      papillomavirus (HPV). Although most women are able to clear an HPV infection,
      some develop persistent infections that may lead to cancer. The determinants of
      persistent infection are largely unknown. We have previously shown that women
      developing carcinoma in situ of the cervix uteri have higher titers of HPV 16
      long before development of cervical neoplasia, indicating that the immune
      response to HPV is important in determining the outcome of an infection. The HLA
      class II alleles DRB1*1501 and DQB1*0602 have previously been associated with an
      increased risk of HPV infection, and carriers of these alleles also tend to have
      more long-term infections. Together these results indicate that certain HLA
      alleles may affect the ability to control the HPV copy number. To evaluate this
      possibility, we studied the HLA class II DRB1*1501-DQB1*0602 haplotype, as well
      as the alleles individually, and the HPV 16 titer in 928 women from a
      retrospective case-control study (441 cases and 487 controls). Carriers of the
      haplotype DRB1*1501-DQB1*0602 allele have a significantly higher HPV 16 titer
      compared to noncarriers (t-test with unequal variance, p = 0.017). An association
      was found between the HLA haplotype carrier frequency and HPV 16 titer (Mantel
      Haenszel statistics p = 0.005). To study whether titer is related to the
      persistency of infection, women were divided into groups with long-term and short
      term infection. A strong correlation is seen between long-term infection and high
      viral load and between short-term infection and low viral load. These results
      show that host genetic factors, e.g., variation at the HLA class II loci studied,
      may affect the immune reaction to the virus and thereby indirectly increase the
      susceptibility to carcinoma in situ of the cervix uteri.

PMID- 12237893
TI  - Proteasome inhibitors reconstitute the presentation of cytotoxic T-cell epitopes
      in Epstein-Barr virus-associated tumors.
AB  - EBV-infected cells and EBV-associated tumors may evade CTL recognition by
      defective antigen processing, resulting in poor presentation of CTL epitopes.
      Since the proteasome is the major source of MHC class I-presented peptides, we
      analyzed the effect of proteasome inhibitors on the expression of surface HLA
      class I and the generation of EBV-derived CTL epitopes presented by the HLA-A2
      and HLA-A11 alleles. Treatment with covalent and reversible inhibitors of the
      proteasome partially reduced the total and allele-specific expression of surface
      HLA class I in EBV-carrying LCLs. HLA-A2 expression was also decreased by
      treatment with leupeptin and bestatin, while HLA-A11 expression was affected by
      treatment with phenanthroline. Despite their general inhibitory effect on HLA
      class I expression, all proteasome inhibitors tested enhanced the presentation of
      2 subdominant HLA-A2 epitopes from EBV LMP1 and LMP2, while the presentation of
      the immunodominant HLA-A11-restricted epitope from EBNA4 was inhibited by MG132
      and lactacystin and increased by ZL(3)VS. Treatment with ZL(3)VS restored the
      presentation of endogenously expressed EBNA4 in 1 HLA-A11-positive BL cell line.
      These findings suggest that specific inhibitors of the proteasome may be used to
      increase the antigenicity of virus-infected and malignant cells that are per se
      inefficient at generating particular CTL target epitopes.

PMID- 12237894
TI  - Prognostic value of the quantitative measurement of the oncoprotein p185(Her
      2/neu) in a group of patients with breast cancer and positive node involvement.
AB  - Our study attempts to determine the prognostic value of the quantitative
      measurement of the oncoprotein p185(Her-2/neu) in a group of patients with breast
      cancer and positive node involvement. In a series of 217 patients with breast
      cancer and positive nodes in whom the oncoprotein p185 was quantitatively
      determined by ELISA, we analyzed the clinico-pathological variables including
      age, menopausal status, tumor size, number of affected nodes, type and histology
      grade and the molecular variables such as the oestrogen and progesterone
      receptors (ER and PR, respectively), pS2 and Cathepsin D (CD). Using 260 fmol/mg
      protein as a cut-off point, 18% of the tumors presented as overexpressing p185.
      The p185 showed no relationship with any of the clinico-pathological variables
      studied except that its concentration was elevated in ductal and lobular
      histology types and in the moderate and poorly differentiated histology grades.
      With a median follow-up of 50 months (range 1-90), the univariate analysis of
      disease-free survival (DFS) and overall survival (OS) showed that the histology
      grade, tumor size, the number of infiltrated nodes, the p185 and the ER were the
      variables associated with the clinical course of the disease in the patients. In
      the multivariate analysis, however, only the tumor size, number of affected
      ganglia, the p185 and the ER remained associated with the clinical progression of
      the disease. The patients with p185 overexpression had a risk, not only of
      relapse but also death from the disease, of more than twice that of the patients
      who had normal p185 concentrations. When the p185 was divided into 3 categories
      based on +/-1 x SD above or below the mean, the patients with high and low p185
      showed, in the univariate analysis, a similar relationship with DFS but not with
      OS. In the multivariate analysis, both with the DFS as with the OS, only a high
      p185 concentration retained its association with the clinical course of the
      disease in the patients. Our results suggest that by quantitatively determining
      (using ELISA) the p185 oncoprotein, groups of cancer patients of high risk could
      be better identified for more effective clinical management.

PMID- 12237895
TI  - Serum HCG beta, CA 72-4 and CEA are independent prognostic factors in colorectal
      cancer.
AB  - In colorectal cancer, stage is considered to be the strongest prognostic factor,
      but also serum tumour markers have been reported to be of prognostic value. The
      aim of our study was to investigate the prognostic value of serum
      carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 72-4 and free beta subunit of
      human chorionic gonadotropin (hCG beta) in colorectal cancer. Preoperative serum
      samples were obtained from 204 colorectal cancer patients, including 31 patients
      with Dukes' A, 70 with Dukes' B, 49 with Dukes' C and 54 with Dukes' D cancer.
      The serum levels of CEA, CA 19-9, CA 242 and CA 72-4 were measured with
      commercial kits with cut-off values of 5 microg/L for CEA, 37 kU/L for CA 19-9,
      20 kU/L for CA 242 and 6 kU/L for CA 72-4. The serum hCG beta was quantitated by
      an immunofluorometric assay (IFMA) with 2 pmol/L as a cut-off value. Survival
      analyses were performed with Kaplan-Meier life tables, log-rank test and Cox
      proportional hazards model. The sensitivity was 44% for CEA, 26% for CA 19-9, 36%
      for CA 242, 27% for CA 72-4 and 16% for hCG beta. The overall 5-year survival was
      55%, and in Dukes' A, B, C and D cancers the survival was 89%, 77%, 52% and 3%,
      respectively. Elevated serum values of all markers correlated with worse survival
      (p < 0.001). In Cox multivariate analysis, the strongest prognostic factor was
      Dukes' stage (p < 0.001), followed by tumour location (p = 0.002) and
      preoperative serum markers hCG beta (p = 0.002), CA 72-4 (p = 0.003) and CEA (p =
      0.005). In conclusion, elevated CEA, CA 19-9, CA 242, CA 72-4 and hCG beta relate
      to poor outcome in colorectal cancer. In multivariate analysis, independent
      prognostic significance was observed with hCG beta, CA 72-4 and CEA.

PMID- 12237896
TI  - Circulating levels of insulin-like growth factor-I and risk of ovarian cancer.
AB  - Insulin-like growth factor (IGF)-I, a mitogenic and anti-apoptotic peptide, has
      been implicated in the development of several cancers. We hypothesized that high
      circulating IGF-I concentrations may be associated with an increased risk of
      ovarian cancer. A case-control study was nested within 3 prospective cohorts in
      New York (USA), Umea (Sweden) and Milan (Italy). One hundred thirty-two women
      with primary invasive epithelial ovarian cancer diagnosed at least 1 year after
      blood donation were case subjects. For each case, 2 control subjects were
      selected, matching the case subject on cohort, menopausal status, age and date of
      recruitment (n = 263). Only women who did not use exogenous hormones at blood
      donation were included in the study. There was no association between IGF-I
      concentrations and ovarian cancer risk in the study group as a whole. In analyses
      restricted to subjects who had developed ovarian cancer at a young age (<55),
      circulating IGF-I was directly and strongly associated with ovarian cancer risk
      (OR = 4.97; 95% CI = 1.22-20.2 for the top vs. the bottom IGF-I tertile after
      adjustment for parity, BMI categories and smoking). There was no significant
      association of IGF binding protein-3 with ovarian cancer risk. We found a strong
      direct relationship between circulating IGF-I levels and risk of developing
      ovarian cancer before age 55. Additional, larger studies of this association are
      needed to provide more precise estimates of effect.

PMID- 12237897
TI  - Survival in prospectively ascertained familial breast cancer: analysis of a
      series stratified by tumour characteristics, BRCA mutations and oophorectomy.
AB  - Dedicated clinics have been established for the early diagnosis and treatment of
      women at risk for inherited breast cancer, but the effects of such interventions
      are currently unproven. This second report on prospectively diagnosed inherited
      breast cancer from the European collaborating centres supports the previous
      conclusions and adds information on genetic heterogeneity and the effect of
      oophorectomy. Of 249 patients, 20% had carcinoma in situ (CIS), 54% had
      infiltrating cancer without spread (CaN0) and 26% had cancer with spread (CaN+).
      Five-year survival was 100% for CIS, 94% for CaN0 and 72% for CaN+ (p = 0.007).
      Thirty-six patients had BRCA1 mutations, and 8 had BRCA2 mutations. Presence of
      BRCA1 mutation was associated with infiltrating cancer, high grade and lack of
      oestrogen receptor (p < 0.05 for all 3 characteristics). For BRCA1 mutation
      carriers, 5-year survival was 63% vs. 91% for noncarriers (p = 0.04). For CaN0
      patients, mutation carriers had 75% 5-year disease-free survival vs. 96% for
      noncarriers (p = 0.01). Twenty-one of the mutation carriers had undergone
      prophylactic oophorectomy, prior to or within 6 months of diagnosis in 13 cases.
      All but 1 relapse occurred in the 15 who had kept their ovaries, (p < 0.01); no
      relapse occurred in those who had removed the ovaries within 6 months (p = 0.04)
      Contralateral cancer was more frequently observed in mutation noncarriers, but
      this finding did not reach statistical significance. Our findings support the
      concept that BRCA1 cancer is biologically different from other inherited breast
      cancers. While current screening protocols appear satisfactory for the majority
      of women at risk of familial breast cancer, this may not be the case for BRCA1
      mutation carriers. The observed effect of oophorectomy was striking.

PMID- 12237898
TI  - Cigarette smoking, alcohol consumption and subsequent gastric cancer risk by
      subsite and histologic type.
AB  - The effect of cigarette smoking or alcohol consumption on the risk of gastric
      cancer has not been clarified. We investigated this relationship, considering the
      anatomic subsite and histologic type of gastric cancer. A total of 19,657 men
      (aged 40-59 years at baseline), who responded to the baseline questionnaire and
      reported no serious illness at that time, were followed for 10 years, from
      January 1990 to December 1999. Gastric cancer was confirmed histologically in 293
      men. Smoking was associated with an increased risk of the differentiated type of
      distal gastric cancer; compared to the group who never smoked, the adjusted rate
      ratios (RRs) of gastric cancer for past and current smokers were 2.0 (95% CI 1.1
      3.7) and 2.1 (95% CI 1.2-3.6), respectively. No association was observed between
      cigarette smoking and risk of the undifferentiated type of distal gastric cancer
      except for a suggestive association with cardia cancer. For alcohol consumption,
      elevated risk was suggested only for cardia cancer of all histologic types,
      though the relationship failed to reach significance. Among those who drank
      alcohol at least once per week, RRs for ethanol intake of 2.7-161.0, 162.0-322.0
      and 322.5+ g/week compared to those who drank 0-3 times/month were 2.5 (95% CI
      0.7-9.5), 3.3 (0.9-11.6) and 3.0 (0.8-11.1), respectively (p(trend) = 0.66). In
      conclusion, our results confirm that smoking is related to gastric cancer of the
      differentiated type. Further studies with more cases are needed to detect a
      positive association between cigarette smoking or alcohol consumption and cardia
      cancer.

PMID- 12237899
TI  - Antiproliferative, antiangiogenic and proapoptotic activity of h-R3: A humanized
      anti-EGFR antibody.
AB  - The epidermal growth factor receptor (EGFR) proto-oncogene is frequently
      overexpressed in tumors of epithelial origin. This event is thought to be
      causative for tumor development and progression and henceforth associated with
      poor prognosis. The recent considerable interest in developing EGFR-targeting
      agents resulted in derivation of the monoclonal, humanized, neutralizing antibody
      h-R3, which binds to the extracellular domain of EGFR with high affinity and
      strongly inhibits EGFR-dependent cellular transformation. Thus, treatment of A431
      squamous cell carcinoma cells with h-R3 in either 2-dimensional or 3-dimensional
      culture resulted in appreciable antimitotic effects through induction of the G1
      arrest. Although h-R3 does not appear to have a direct proapoptotic activity in
      this setting, it inhibits production of the vascular endothelial growth factor
      (VEGF) by A431 cells both in vitro and in vivo. In the latter case, h-R3
      treatment (0.25-1 mg/mouse; every other day per 2 weeks) not only significantly
      reduced VEGF mRNA expression of A431 tumors growing subcutaneously in SCID mice
      but also resulted in reduction of the overall microvascular density (MVD),
      disappearance of dilated "mother vessels," as well as in suppression of tumor
      growth followed by regression of established tumors. This apparent antiangiogenic
      activity of h-R3 was associated with reduction in Ki67-positive tumor cell
      fraction and (unlike in vitro) also with an elevated apoptotic index, the latter
      indicative of a cytotoxic mode of action in vivo. Taken together, h-R3 is a
      promising new antagonist of the EGFR oncogene, the anticancer properties of which
      are associated with combined and potent antiproliferative, antiangiogenic and
      proapoptotic activity.

PMID- 12237900
TI  - Automated diagnosis of pigmented skin lesions.
AB  - Since advanced melanoma remains practically incurable, early detection is an
      important step toward a reduction in mortality. High expectations are entertained
      for a technique known as dermoscopy or epiluminescence light microscopy; however,
      evaluation of pigmented skin lesions by this method is often extremely complex
      and subjective. To obviate the problem of qualitative interpretation, methods
      based on mathematical analysis of pigmented skin lesions, such as digital
      dermoscopy analysis, have been developed. In the present study, we used a digital
      dermoscopy analyzer (DBDermo-Mips system) to evaluate a series of 588 excised,
      clinically atypical, flat pigmented skin lesions (371 benign, 217 malignant). The
      analyzer evaluated 48 parameters grouped into 4 categories (geometries, colors,
      textures and islands of color), which were used to train an artificial neural
      network. To evaluate the diagnostic performance of the neural network and to
      check it during the training process, we used the error area over the receiver
      operating characteristic curve. The discriminating power of the digital
      dermoscopy analyzer plus artificial neural network was compared with histologic
      diagnosis. A feature selection procedure indicated that as few as 13 of the
      variables were sufficient to discriminate the 2 groups of lesions, and this also
      ensured high generalization power. The artificial neural network designed with
      these variables enabled a diagnostic accuracy of about 94%. In conclusion, the
      good diagnostic performance and high speed in reading and analyzing lesions (real
      time) of our method constitute an important step in the direction of automated
      diagnosis of pigmented skin lesions.

PMID- 12237901
TI  - PLU-1 nuclear protein, which is upregulated in breast cancer, shows restricted
      expression in normal human adult tissues: a new cancer/testis antigen?
AB  - The PLU-1 gene is expressed at the level of message in breast cancers and breast
      cancer cell lines and shows restricted expression in normal adult tissues with
      the exception of testis. The predicted protein sequence contains several domains,
      including the PLU domain, which is shared by other proteins involved in
      transcription and/or development. We have developed a polyclonal antiserum to a C
      terminal fragment of the PLU-1 protein, which shows little homology to other
      family members. Immunohistochemical analysis with the antiserum alpha-PLU-1C
      confirmed the nuclear localisation of PLU-1. alpha-PLU-1C also reacted with the
      mouse homologue of PLU-1 (mPlu-1) but not with the closest family member, RBP2.
      Using Western blot analysis, PLU-1 was shown to be well expressed in breast
      cancers and breast cancer cell lines, while it was not detected in a range of
      normal adult tissues. Our results suggest that the PLU-1 protein may belong to
      the class of testis/cancer antigens.

PMID- 12237907
TI  - Cancer clinical trial recruitment.

PMID- 12237902
TI  - Increasing endogenous ceramide using inhibitors of sphingolipid metabolism
      maximizes ionizing radiation-induced mitochondrial injury and apoptotic cell
      killing.
AB  - To enhance the killing effects of ionizing radiation, we amplified the endogenous
      ceramide signal in Jurkat cell cultures using 3 different inhibitors of
      sphingolipid metabolism: DL-PDMP, D-MAPP and imipramine. Of the various possible
      drug combinations, only DL-PDMP (20 microM) + imipramine (20 microM) and DL-PDMP
      (20 microM) + imipramine (20 microM) + D-MAPP (5 microM) induced a major increase
      in ceramide levels, reaching 240% and 340% of control values, respectively, after
      incubation for 48 hr. With these models, we demonstrate that endogenously formed
      ceramide triggers time- and concentration-dependent apoptosis through induction
      of mitochondrial injury and activation of the caspase pathway. Cellular
      dysfunction includes alterations to the cellular redox potential, as assessed by
      the generation of ROS and total glutathione depletion, and a drop in Delta
      Psi(m). A parallel elevation of mitochondrial ceramide levels was also observed.
      The combination of DL-PDMP + imipramine +/- D-MAPP with 10 Gy irradiation
      produced cumulative effects leading to apoptosis via mitochondrial collapse and
      activation of the caspase cascade. The association efficiency was confirmed in
      normal and acid sphingomyelinase-deficient lymphoid cell lines. Taken together,
      these results suggest that increasing endogenous ceramide levels may potentially
      be very valuable when combined with ionizing radiation in tumor therapy.

PMID- 12237909
TI  - Morphology and therapeutic strategies for neuroendocrine tumors of the
      genitourinary tract.
AB  - BACKGROUND: Although many articles have been published regarding neuroendocrine
      tumors (NET) and neuroendocrine carcinomas of both low- and high-grade malignancy
      (NEC) of the genitourinary tract, the histologic diagnosis and therapeutic
      strategies for treating these entities remains difficult. In the current study
      the author discusses the significant differences between NET and NEC of the
      urinary bladder and the prostate, including therapeutic consequences. METHODS:
      Four hundred eighty neoplasms of the urinary bladder and prostate with a small
      cell pattern were analyzed not only on slides stained with hematoxylin and eosin
      but also by means of immunohistochemical stains demonstrating a neuroendocrine
      origin. The avidin-biotin complex method was used with the following markers: MIB
      1, chromogranin A (Chr A), synaptophysin (SNP), cytokeratin (CK) 34betaE12, CK20,
      androgen receptor (AR), and prostate specific antigen (PSA). RESULTS: Twenty
      tumors of the urinary bladder and 26 of the prostate demonstrated a diffuse
      neuroendocrine pattern. Only two patients were found to have a low-grade NEC of
      the prostate with a low proliferative index but strong expression of
      neuroendocrine markers. All other patients with small cell neuroendocrine
      carcinomas of the bladder and prostate demonstrated extremely high proliferation
      activity (>80%) and expressed Chr A and SNP. CK34betaE12, 20, PSA, and AR were
      not found to be expressed. The mean survival time was 6.9 months. Fourteen of 20
      patients with NEC of the urinary bladder died of the disease and 19 of 24
      patients with prostatic NEC died. The therapy for urinary bladder NEC was
      repeated transurethral resection and antiandrogen therapy was given for NEC of
      the prostate. Only one patient was treated with chemotherapy, which to the
      author's knowledge currently is the only treatment for NECs of the genitourinary
      tract. CONCLUSIONS: Undifferentiated carcinomas of the urinary bladder and
      prostate should be analyzed not only by means of hematoxylin and eosin but also
      by immunohistochemical staining for Chr A and SNP to demonstrate a neuroendocrine
      origin. Because the prognosis of small cell NECs is very poor, pathologists
      should indicate in their final report the peculiarities of small cell NECs of the
      prostate and the urinary bladder with special emphasis on different therapeutic
      strategies.

PMID- 12237908
TI  - Variations in breast carcinoma treatment in older medicare beneficiaries: is it
      black or white.
AB  - BACKGROUND: To evaluate associations between race and breast carcinoma treatment.
      METHODS: Data from 984 black and 849 white Medicare beneficiaries 67 years or
      older with local breast carcinoma and a subset of 732 surviving women interviewed
      3-4 years posttreatment were used to calculate adjusted odds of treatment,
      controlling for age, comorbidity, attitudes, region, and area measures of
      socioeconomic and health care resources. RESULTS: Sixty-seven percent of women
      received a mastectomy and 33% received breast-conserving surgery. The odds of
      radiation omission were 48% higher (95% confidence interval [CI] 1.01-2.19) for
      blacks than for whites after considering covariates, but the absolute number of
      women who failed to receive this modality was small (11%). In race-stratified
      models, the odds of having radiation omitted were significantly higher among
      blacks living greater distances from a cancer center (vs. lesser) or living in
      areas with high poverty (vs. low), but these factors did not affect radiation use
      among whites. Among those interviewed, blacks reported perceiving more ageism and
      racism in the health care system than whites (P = 0.001). The independent odds of
      receiving mastectomy (vs. breast conservation and radiation) were 2.72 times
      higher (95% CI 1.25-5.92) among women reporting the highest quartile of perceived
      ageism scores, compared with the lowest, and higher perceived ageism tended to be
      associated with higher odds of radiation omission (P = 0.06). CONCLUSIONS: Older
      black women with localized breast carcinoma may have a different experience
      obtaining treatment than their white counterparts. The absolute number of women
      receiving nonstandard care was small and the effects were small to moderate.
      However, if these patterns persist, it will be important to evaluate whether such
      experiences contribute to within-stage race mortality disparities.

PMID- 12237910
TI  - Intake of dietary folate vitamers and risk of colorectal carcinoma: results from
      The Netherlands Cohort Study.
AB  - BACKGROUND: Several studies have reported inverse associations between folate
      intake and colorectal carcinoma risk. Few were prospective studies and none
      evaluated the association between the intake of individual folate vitamers and
      colorectal carcinoma risk. METHODS: The aim of the current study was to
      investigate the relationship between dietary folate intake and the risk of
      colorectal carcinoma in a large prospective cohort study in The Netherlands
      comprising 120,852 men and women aged 55-69 years. After 7.3 years of follow-up,
      760 colon and 411 rectal carcinoma cases were available for analysis. Data
      processing and analysis used the case-cohort approach. A new Dutch database was
      used to estimate intakes of total and individual folate vitamers. RESULTS:
      Analyses adjusted for age, energy intake, family history of colorectal carcinoma,
      alcohol, vitamin C, iron, and dietary fiber intake yielded an inverse association
      between colon carcinoma risk and total dietary folate intake (rate ratio
      [RR]highest vs. lowest quintile, men: 0.73; 95% confidence interval [CI], 0.46
      1.17, P trend = 0.03; women: 0.68; 95% CI, 0.39-1.20, P trend = 0.18). An inverse
      association between rectal carcinoma and total dietary folate intake was found
      only among men (RR highest vs. lowest quintile, men: 0.66; 95% CI, 0.35-1.21, P
      trend = 0.03). Analyses showed no clear difference in colorectal carcinoma risk
      associated with intake of different folate vitamers. CONCLUSIONS: Dietary folate
      intake was related inversely to colon and male rectal carcinoma risk.

PMID- 12237911
TI  - Prognostic factors for the survival of patients with esophageal carcinoma in the
      U.S.: the importance of tumor length and lymph node status.
AB  - BACKGROUND: The current TNM classification system does not consider tumor length
      or the number of lymph nodes in the staging and classification scheme for
      patients with esophageal carcinoma. Using data from the National Cancer Institute
      SEER Program, the authors explored the effect of tumor length and number of
      positive lymph nodes on survival in patients with esophageal carcinoma. METHODS:
      Patients with esophageal adenocarcinoma or squamous cell carcinoma were
      subgrouped according to historic stage with localized, regional, or distant
      disease. Demographic factors (age at diagnosis, race, and gender) and tumor
      characteristics (morphology, histologic grade, tumor length, primary site, depth
      of invasion, number of positive lymph nodes, proportion of positive lymph nodes
      dissected, and distant metastatic sites) were examined. RESULTS: Overall factors
      that were associated with an increased mortality risk included increasing age at
      diagnosis, black race versus white race, histologic grade, primary tumor site in
      the lower esophagus and abdomen versus upper regions, and increasing depth of
      invasion. Among patients with regional disease, the number of positive lymph
      nodes (>/= 5 vs. < 5) was related to an increasing risk (hazard ratio [HR], 1.29;
      95% confidence interval [95%CI], 1.06-1.56). The proportion of positive lymph
      nodes compared with the number of lymph nodes dissected conferred an increased
      risk (HR, 1.63; 95%CI, 1.26-2.11). Among patients with distant disease, sites
      other than distant lymph nodes implied an increased mortality risk (HR, 1.37;
      95%CI, 1.37-1.65). Tumor length was an independent predictor of mortality when
      controlling for depth of invasion in patients with localized disease (HR, 1.15;
      95%CI, 1.08-1.21). CONCLUSIONS: Tumor length, the number of involved lymph nodes,
      and the ratio of positive lymph nodes are important prognostic factors for
      survival in patients with esophageal carcinoma. A revised TNM classification
      system for patients with esophageal carcinoma might consider adding tumor length
      and number of positive lymph nodes as two important prognostic factors.

PMID- 12237912
TI  - Gemcitabine plus epirubicin in patients with advanced urothelial carcinoma who
      are not eligible for platinum-based regimens.
AB  - BACKGROUND: The objective of this study was to evaluate the efficacy and toxicity
      of gemcitabine plus epirubicin in previously untreated patients with advanced
      urothelial carcinoma who were not eligible for cisplatin-based regimens. METHODS:
      Patients with advanced urothelial carcinoma and at least one of the following
      characteristics were eligible: impaired renal function (creatinine clearance < 60
      mL per minute), an Eastern Cooperative Oncology Group performance status (PS)
      >or= 2, and age >or= 75 years. The treatment included epirubicin 70 mg/m(2) as an
      intravenous bolus on Day 1 and gemcitabine 1000 mg/m(2) over 30 minutes on Days 1
      and 8 of a 21-day cycle. RESULTS: Thirty-eight patients entered the study, and a
      total of 152 cycles were administered, with a median of 4 cycles per patient
      (range, 1-6 cycles per patient). The following Grade 3-4 hematologic toxicities
      were reported (percent of cycles): neutropenia, 22.4%; anemia, 11.2%; and
      thrombocytopenia, 6.5%. No cardiac, renal, or hepatic toxicities were observed.
      Dose intensities of epirubicin and gemcitabine were 19.6 mg/m(2) per week (84%)
      and 532.2 mg/m(2) per week (80%), respectively. There were 2 complete responses
      (5.3%), 13 partial responses (34.2%), 11 patients with stable disease (28.9%),
      and 12 patients with progressive disease (31.6%), for an overall response rate of
      39.5% (95% confidence interval, 25.1-55.1). The median progression free survival
      (PFS) and overall survival (OS) rates were 4.8 months and 8.0 months,
      respectively. The 1-year survival rate was 38%, and the median PFS and OS were
      6.4 months and 16.4 months, respectively, in patients with PS 0-1. Thirty
      patients were symptomatic: Seventeen patients (56.7%) achieved a complete
      response, and 5 patients (16.7%) achieved a partial symptomatic response.
      CONCLUSIONS: At the doses given in this study, gemcitabine and epirubicin had a
      good tolerability profile with interesting activity in patients with advanced
      urothelial carcinoma who were not fit for cisplatin-based regimens.

PMID- 12237913
TI  - A comprehensive and novel predictive modeling technique using detailed pathology
      factors in men with localized prostate carcinoma.
AB  - BACKGROUND: The purpose of the current study was to evaluate modeling strategies
      using sextant core prostate biopsy specimen data that would best predict
      biochemical control in patients with localized prostate carcinoma treated with
      permanent prostate brachytherapy (PPB). METHODS: One thousand four hundred
      seventy-seven patients underwent PPB between 1992 and 2000. The authors
      restricted analysis to those patients who had sextant biopsies (n = 1073). A
      central pathology review was undertaken on all specimens. Treatment consisted of
      PPB with either I-125 or Pd-103 prescribed to 144 Gy or 140 Gy, respectively. Two
      hundred twenty-eight patients (21%) received PPB in combination with external
      radiotherapy and 333 patients (31%) received neoadjuvant hormones. In addition to
      clinical stage, biopsy Gleason sum, and pretreatment prostate specific antigen
      (pretx-PSA), the following detailed biopsy variables were considered: mean
      percentage of cancer in an involved core; maximum percentage of cancer; mean
      primary and secondary Gleason grades; maximum Gleason grade (primary or
      secondary); percentage of cancer in the apex, mid, and base; percent of cores
      positive; maximum primary and secondary Gleason grades in apex, mid, and base;
      maximum percent cancer in apex, mid, and base; maximum Gleason grade in apex,
      mid, and base; maximum primary Gleason grade; and maximum secondary Gleason
      grade. In all, 23 biopsy variables were considered. Four modeling strategies were
      compared. As a base model, the authors considered the pretx-PSA, clinical stage,
      and biopsy Gleason sum as predictors. For the second model, the authors added
      percent of cores positive. The third modeling strategy was to use stepwise
      variable selection to select only those variables (from the total pool of 26)
      that were statistically significant. The fourth strategy was to apply principal
      components analysis, which has theoretical advantages over the other strategies.
      Principal components analysis creates component scores that account for maximum
      variance in the predictors. RESULTS: The median followup of the study cohort was
      36 months (range, 6-92), and the Kattan modification of the American Society for
      Therapeutic Radiology and Oncology (ASTRO) definition was used to define PSA
      freedom from recurrence (PSA-FFR). The four models were compared in their ability
      to predict PSA-FFR as measured by the Somers D rank correlation coefficient. The
      Somers D rank correlation coefficients were then corrected for optimism with use
      of bootstrapping. The results for the four models were 0.32, 0.34, 0.37, and
      0.39, respectively. CONCLUSIONS: The current study shows that the use of
      principal components analysis with additional pathology data is a more
      discriminating model in predicting outcome in prostate carcinoma than other
      conventional methods and can also be used to model outcome predictions for
      patients treated with radical prostatectomy and external beam.

PMID- 12237914
TI  - Resources and use of the intensive care unit in patients who undergo surgery for
      ovarian carcinoma.
AB  - BACKGROUND: The objective of the current study was to determine the association
      of age, comorbid illness, and length of stay (LOS) in the intensive care unit
      (ICU) in women who underwent oophorectomy for ovarian carcinoma. METHODS: The
      authors conducted a population-based analysis of all women with a primary or
      secondary diagnosis of ovarian carcinoma who underwent oophorectomy between 1994
      1999. Chi-square tests and Student t tests were used to determined differences in
      means or proportions. Multivariate regression methods were used to build
      predictive models. RESULTS: Of 8109 women who were admitted, 1412 women underwent
      oophorectomy, 1045 of 1412 women (74%) underwent hysterectomy, 325 of 1412 women
      (23%) underwent intestinal surgery, and 296 of 1412 women (21%) were admitted to
      the ICU. Overall (+/- standard deviation) LOS was 8.3 days +/- 6.90 days, and the
      total charges were $16,675 +/- $15,590 (1999 dollars). Patients who underwent
      intestinal surgery were older (62.5 years vs. 57.1 years; P = 0.01), had a longer
      LOS (11.62 days vs. 7.33 days; P = 0.01), had a longer ICU stay (1.15 days vs.
      0.58 days; P = 0.01), and had a higher mean Charlson Comorbidity Index (CCI)
      (16.01 vs. 8.73; P = 0.01) compared with patients who did not undergo intestinal
      surgery. Multivariate regression analysis revealed that age, intestinal surgery,
      CCI, ICU stay, and African-American race were associated with LOS and contributed
      indirectly to total charges, whereas age and ICU say were the two most important
      direct determinants of total charges. CONCLUSIONS: Advancing age, ICU stay,
      intestinal surgery, African-American race, and comorbid illness were the most
      prominent predictors of LOS, whereas age and ICU stay were the most important
      factors predicting total charges in women who underwent oophorectomy for ovarian
      carcinoma.

PMID- 12237915
TI  - Apoptosis and apoptosis-related factors Bcl-2, Bax, tumor necrosis factor-alpha,
      and NF-kappaB in human endometrial hyperplasia and carcinoma.
AB  - BACKGROUND: Apoptosis controls cell homeostasis in the endometrium during normal
      menstrual cycles, and morphologic studies have suggested its association with the
      development of endometrial carcinoma. Apoptosis is regulated by several genes,
      especially those of the Bcl-2 gene family, but their significance in endometrial
      pathologies is not well understood. METHODS: To study the role and regulation of
      apoptosis in endometrial hyperplasia and carcinoma, human endometrial specimens
      were analyzed using in situ 3'-end labeling of apoptotic cells and in situ
      hybridization and immunohistochemistry of apoptosis-related factors. RESULTS:
      Apoptosis was scarce in normal proliferating endometrium as well as in simplex,
      complex, and atypical hyperplasia and was low in Grade I adenocarcinoma. In Grade
      II adenocarcinoma a significant increase in the rate of apoptosis was observed.
      Apoptosis decreased in Grade III adenocarcinoma, but it was still higher than in
      normal or hyperplastic endometrium. Bcl-2 and Bax were expressed in normal and
      hyperplastic endometrium, and the Bcl-2/Bax ratio was lower in endometrial
      carcinoma. Tumor necrosis factor-alpha was expressed in normal endometrium and
      simplex and complex hyperplasia, but it was down-regulated in atypical
      hyperplasia and endometrial carcinoma. The transcription factor NF-kappaB was
      present in proliferating endometrium and in endometrial hyperplasia, but its
      expression was lower in carcinoma. CONCLUSIONS: In endometrial proliferation and
      hyperplasia a low rate of apoptosis is present. In Grade I carcinoma the rate of
      apoptosis is decreased, but the rate is subsequently increased in advanced
      carcinoma. The decrease in the rate of apoptosis in Grade III adenocarcinoma may
      reflect loss of control of cell homeostasis, decreased differentiation, and
      increased malignancy.

PMID- 12237916
TI  - A Phase I/II trial of concurrent docetaxel and radiation after induction
      chemotherapy in patients with poor prognosis squamous cell carcinoma of the head
      and neck.
AB  - BACKGROUND: The authors conducted a Phase I/II study in patients with a poor
      prognosis who had locally advanced squamous cell carcinoma of the head and neck
      (SCCHN) and who were treated initially with induction chemotherapy. Patients were
      treated with weekly docetaxel and concurrent daily fractionated radiation therapy
      to determine the maximum tolerated dose (MTD) of docetaxel and the efficacy of
      the regimen. METHODS: Twenty-two patients were enrolled, and 21 patients were
      treated. Eight patients had Stage III SCCHN, and 13 patients had Stage IV SCCHN
      without distant metastases and were treated first with 2-3 cycles of induction
      chemotherapy, which consisted of cisplatin plus 5-fluorouracil with or without
      leucovorin. Patients with a poor prognosis were identified as those who achieved
      a partial response to induction treatment, achieved a complete response with a
      positive biopsy, or were at high risk for developing recurrent disease. Patients
      were treated subsequently with concurrent, escalating doses of docetaxel (given
      weekly x 6) and once daily 200-centigray radiation fractions. RESULTS: Three
      patients were treated with a weekly docetaxel dose of 20 mg/m(2) without dose
      limiting toxicity (DLT). Both patients who were treated at the next dose level of
      30 mg/m(2) experienced DLT. A dose of 25 mg/m(2) was studied without DLT in the
      16 patients who were treated, establishing this as the MTD. Sixty-seven percent
      of the patients are alive without disease at a median follow-up of 35 months
      (range, 12-59 months) after the initiation of chemoradiotherapy. CONCLUSIONS: The
      MTD of weekly docetaxel with concurrent daily radiation therapy in the
      postinduction setting was 25 mg/m(2). Disease free survival data from this study
      were good and indicated that this regimen was effective in the treatment of
      patients with SCCHN who had a poor prognosis.

PMID- 12237917
TI  - Transcriptional expression profiles of oral squamous cell carcinomas.
AB  - BACKGROUND: Currently, the classification of oral squamous cell carcinoma (OSCC)
      depends heavily on the clinical and pathologic examination of tissue. This system
      can lead to the classification of potentially heterogeneous tumors into single
      groups when they may have different degrees of aggressiveness. No system to date
      has incorporated genetic changes as a factor by which to classify OSCC tumors.
      METHODS: To test the hypothesis that OSCC has a genome-wide genetic expression
      profile that differs from normal oral tissue and that transcriptional expression
      profiling can be used to characterize the heterogeneity among tumors, the authors
      examined the genetic expression profiles of 26 invasive squamous cell carcinomas
      of the oral cavity and oropharynx, 2 premalignant lesions, and 18 normal oral
      tissue samples using oligonucleotide arrays that contained probes representing
      approximately 7000 full-length human genes. RESULTS: Using hierarchical
      clustering analysis, the data show that oral carcinomas are distinguishable from
      normal oral tissue based on genome-wide transcriptional expression patterns.
      However, there is genetic expression profile heterogeneity among tumors of a
      particular histopathologic grade and stage. In addition, using a statistical
      approach that integrated normalization and regression analysis, the authors found
      314 genes that were expressed differentially in the OSCC samples with statistical
      significance (P <or= 0.05). Of these, 239 genes were overexpressed in the OSCC
      samples, whereas 75 genes were down-regulated. CONCLUSIONS: No statistically
      significant differences in gene expression were found between early-stage disease
      and late-stage disease or between metastatic tumors and nonmetastatic tumors. The
      implications of these findings for the prediction of clinical outcome and for the
      discovery of new OSCC tumor markers are discussed.

PMID- 12237918
TI  - Improved outcomes in patients with osteogenic sarcoma of the head and neck.
AB  - BACKGROUND: The current study reviews the authors' recent institutional
      experience in the treatment of osteosarcoma of the head and neck (OSHN). METHODS:
      The clinical records of 44 patients who were treated between 1981 and 1998 for
      OSHN were reviewed retrospectively. Archived histologic material was reviewed and
      data were analyzed to identify factors predictive of disease control and
      survival. Outcomes were compared with a previously reported historic cohort
      treated at the study institution. RESULTS: Patients ranged in age from 6 to 64
      years (median, 31 years). The mandible was the primary site in 18 patients (41%),
      the maxilla in 20 patients (45%), and the skull in 6 patients (14%). Surgery was
      employed in all 44 patients, neoadjuvant chemotherapy was administered in 30
      patients (68%), and postoperative radiation therapy was given to 7 patients
      (16%). The surgical excision margins were positive in 13 patients (30%). High
      grade lesions were reported in 50% patients and low-grade lesions were noted in
      18% of patients (grade was not assessable in 32%). Histologic response was
      "unfavorable" in 22 of 30 patients (73%) who were treated with neoadjuvant
      chemotherapy. The 3-year overall, disease-specific, and recurrence-free survival
      rates were approximately 81%, 81%, and 73%, respectively (median follow-up of 41
      months). Positive surgical margins were found to be the only significant
      predictor of worse disease-specific survival. Compared with the historical
      cohort, the current experience demonstrated an obvious improvement in the 5-year
      local control (35% vs. 78%), distant metastases (37% vs. 13%), and overall
      survival (23% vs. 70%). CONCLUSIONS: Negative surgical margins were found to be
      the only significant predictor of overall and disease-specific survival. The
      results of the current study represent a considerable improvement over the
      authors' previously published experience and compare favorably with the results
      reported in the literature.

PMID- 12237919
TI  - The continuing increase in the incidence of primary central nervous system non
      Hodgkin lymphoma: a surveillance, epidemiology, and end results analysis.
AB  - BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an extranodal form
      of non-Hodgkin lymphoma arising in the craniospinal axis. The incidence of PCNSL
      appears to be increasing. METHODS: PCNSL incidence data from 1973-1997 were
      obtained from the nine Surveillance, Epidemiology and End Results (SEER)
      registries. To limit the influence of the human immunodeficiency virus on
      incidence rates, data of never-married males and females and persons of unknown
      marital status were excluded. As a surrogate for new technology, SEER data were
      reviewed by dates of diagnosis (surrogate for imaging) and compared with glioma
      incidence (surrogate for stereotactic neurosurgery and improved diagnostic
      neuropathology). Age-adjusted incidence rates were estimated and compared for the
      period prior to computed tomography (CT) (1973-1984) and the magnetic resonance
      imaging (MRI) period (1985-1997). The estimated annual percent change was
      calculated based on linear regression analyses using SEER*STAT. RESULTS: The
      incidence of PCNSL appears to be increasing in all SEER registries examined. All
      age groups demonstrated an increase over time. This increase was observed both in
      the CT era as well as in the MRI era. PCNSL age-adjusted incidence (0.15 to 0.48,
      a 3-fold increase) outpaced that of systemic lymphoma (14.1 to 18.5, a 33%
      increase) for the same registries over the same time periods. The rate of
      increase has begun to slow since 1985; the estimated annual percent change for
      PCNSL was three-fold higher during the period 1973-1985 compared with 1986-1997.
      CONCLUSION: The incidence rate of PCNSL continues to rise. The increase is
      evident in all age groups and in both genders. Data from the current study
      suggest that improved diagnostic tools, such as CT or MRI, cannot explain this
      increase.

PMID- 12237920
TI  - A Phase I-II study of sequential administration of topotecan and oral etoposide
      (toposiomerase I and II inhibitors) in the treatment of patients with small cell
      lung carcinoma.
AB  - BACKGROUND: Topotecan (9-dimethylaminomethyl-10-hydroxycampthothecin) is a new
      topoisomerase I inhibitor with promising efficacy in the treatment of patients
      with small cell lung carcinoma (SCLC). Combination with a topoisomerase II
      inhibitor may potentate the therapeutic effect of topotecan, although there has
      been conflicting preclinical information on the combination. The objectives of
      this study were to establish the maximum tolerated dose and to determine the
      efficacy of the sequential combination of intravenous topotecan and oral
      etoposide in the treatment of patients with SCLC. METHODS: Patients with
      histologically confirmed, limited or extensive stage SCLC were eligible. The dose
      escalation scheme of three cohorts (six patients per cohort) started at
      intravenous topotecan 0.5 mg/m(2) per day for 5 days and oral etoposide 50 mg
      twice daily for 7 days (21-day cycles). Subsequent dose levels involved
      escalation of topotecan to 0.75 mg/m(2) per day and 1.0 mg/m(2) per day for 5
      days. A Phase II study was conducted at one dose level below the maximum
      tolerated dose. The authors alternated the drug sequence with each consecutive
      cycle and compared the hematologic toxicity between the two sequences. RESULTS:
      Thirty-six patients (21 patients with limited disease and 15 patients with
      extensive disease) received a total of 173 courses of sequential combination
      chemotherapy (topotecan --> etoposide, 88 courses; etoposide --> topotecan, 85
      courses). The authors identified dose levels for the Phase II study as follows:
      topotecan, 0.75 mg/m(2) per day for 5 days; and etoposide, 50 mg twice daily for
      7 days. The dose-limiting toxicity was neutropenia. At this dose level, the
      incidence of Grade 3-4 neutropenia and the incidence of Grade 3-4
      thrombocytopenia were 25% and 10.9%, respectively. Two patients died from
      neutropenic sepsis. There was no significant difference in hematologic toxicities
      between the two sequences. Complete and partial response rates were 5.6% and
      55.6%, respectively (limited disease, 9.5% and 66.75%; extensive disease, 0% and
      40%, respectively). The median progression free survival was 31.9 weeks (limited
      disease, 36.1 weeks; extensive disease, 28.9 weeks; 95% confidence interval, 25.6
      36.0 weeks), and the median overall survival was 52.4 weeks (limited disease,
      54.9 weeks; extensive disease, 30.1 weeks; 95% confidence interval, 39.6-57.7
      weeks). CONCLUSIONS: Combination therapy with topoisomerase I and II inhibitors
      is a safe and effective regimen for patients with SCLC. Future research on this
      combination should focus on an oral regimen for patients with extensive disease
      and poor tolerance to cisplatin. The authors recommend an oral dosage of
      topotecan at 1.2 mg/m(2) per day (equivalent to intravenous topotecan at 0.75
      mg/m(2) per day) for 5 days followed by etoposide 50 mg twice daily for 7 days.

PMID- 12237921
TI  - Phase II trial of irinotecan, paclitaxel and carboplatin in patients with
      previously untreated Stage IIIB/IV nonsmall cell lung carcinoma.
AB  - BACKGROUND: This Phase II multicenter, open-label, single-arm study evaluated the
      efficacy and safety of a three-drug combination of irinotecan (CPT-11),
      paclitaxel, and carboplatin in advanced nonsmall cell lung carcinoma (NSCLC).
      METHODS: Patients received repeated 21-day cycles at starting doses of paclitaxel
      175 mg/m(2) administered over 3 hours, followed by carboplatin AUC of 5 over 30
      minutes and CPT-11 at a starting dose level of 100 mg/m(2) over 90 minutes, all
      given on the first day of each cycle. Patients were evaluated for objective tumor
      response, time to tumor progression (TTP), survival, and safety. RESULTS: Forty
      patients were enrolled. Baseline patient characteristics included: median age 58
      years (range, 32-79); 23 males and 17 females; performance status of 0 (21
      patients), 1 (18 patients), or 2 (1 patient); and Stage IIIB (10 patients) and
      Stage IV (30 patients) disease. A median of six cycles (range, one to eight) were
      administered. Grade 3-4 toxicities observed in >/= 10% of the patients included
      neutropenia (78%), asthenia (20%), diarrhea (20%), nausea (18%), vomiting (13%),
      anemia (10%), and dyspnea (10%). Febrile neutropenia occurred in eight patients
      (20%), with one death due to neutropenic sepsis. Twelve of 38 evaluable patients
      had confirmed tumor responses (32%), while 21 (55%) had stable disease (including
      12 patients [32%] with minor responses). Only 13% had disease progression at
      their initial tumor assessment. The median TTP and survival were 5.3 months
      (range, 0.03-6.2 months) and 12.5 months (range 0.3-28.6+ months), respectively.
      The one and two year survival probabilities were 0.50 (95% confidence interval
      [CI], 0.28-0.73) and 0.21 (95% CI, 0.0-0.67), respectively. CONCLUSIONS: The
      combination of CPT-11, paclitaxel, and carboplatin can be safely administered and
      is active in the treatment of advanced NSCLC. Based on the favorable survival
      outcome, this regimen is undergoing evaluation in prospective randomized trials.

PMID- 12237922
TI  - Twenty-five years of clinical research for patients with limited-stage small cell
      lung carcinoma in North America.
AB  - BACKGROUND: To determine the changes in clinical trials and outcomes of patients
      with limited-stage small cell lung carcinoma (SCLC) treated on Phase III
      randomized trials initiated in North America between 1972 and 1992. METHODS:
      Phase III trials from 1972 to 1992 for patients with limited-stage SCLC were
      identified. Patients with limited-stage SCLC treated during a similar time
      interval were also evaluated in the Surveillance, Epidemiology, and End Results
      (SEER) database. Trends were tested in the number of trials, in the number and
      gender of patients entered on trial, and in survival duration over time. RESULTS:
      Thirty trials involving 6564 patients were eligible for analyses. Nineteen trials
      (61%) involving 3626 patients were initiated within the first half of this time
      period (1972-1981). The median of median survival times of all patients treated
      on the control arms of the Phase III trials initiated between 1972 and 1981 and
      between 1982 and 1992 were 12.0 months (range, 10-16 months) and 17.0 months
      (range, 11-20 months), respectively (P < 0.001). Of 26 studies available for
      survival analysis, 5 (19%) showed a statistically significant survival
      prolongation in the experimental arm compared with the control arm with a median
      prolongation of 3.4 months (range, 1-5.2 months). All five evaluated some aspect
      of thoracic radiation therapy. Over a similar time period, there was a 6.4-month
      increase in the median survival of limited-stage SCLC patients listed in the SEER
      database (P < 0.0001) and a more than doubling of the 5-year survival from 5.2%
      to 12.1% (P = 0.0001). CONCLUSIONS: Analyses of the patients with limited-stage
      SCLC treated on Phase III trials in North America initiated between 1972 and 1992
      and those listed in the SEER database show significant improvements in median
      survivals. Furthermore, the 5-year survival of patients with limited-stage SCLC
      listed in the SEER database has more than doubled over the last 25 years. Further
      research will be needed to determine the relative contribution of improved
      therapy, supportive care, and stage migration to this prolongation in survival.

PMID- 12237923
TI  - Evidence of neoangiogenesis and an increase in the number of proliferating cells
      within the bronchial epithelium of smokers.
AB  - BACKGROUND: Normal bronchial epithelium gradually acquires cellular and genetic
      changes that result in the formation of invasive tumors. The objective of this
      study was to evaluate the degree of proliferative change and the amount of
      neovascularization in both normal and preneoplastic lesions in smokers who were
      at high risk for developing lung carcinoma. METHODS: The authors studied
      bronchial biopsy specimens from 7 nonsmokers and 52 smokers. Immunohistochemical
      staining of the specimens with antibodies for the presence of p53 protein, Ki-67
      and CD34 antigens, and vascular endothelial growth factor was performed. The
      proliferation index (PI) was assessed by immunohistochemical staining for Ki-67
      antigen. RESULTS: Overexpression of p53 protein was observed frequently in
      regions of squamous dysplasia and in squamous cell carcinoma tissue. The PI of
      normal epithelium from smokers was increased compared with nonsmokers, and the
      difference was statistically significant (P < 0.05). The microvessel count (MC)
      in normal mucosa obtained from smokers was higher compared with the MC in normal
      mucosa obtained from nonsmokers (P < 0.05). A significant difference in MC also
      was observed between regions of squamous metaplasia or dysplasia with projections
      of capillary loops into the bronchial mucosa and similar lesions without
      capillary loops (P < 0.005); however, there was no difference in either the PI or
      the incidence of p53 overexpression between these groups. CONCLUSIONS: These
      results show that smoking appears to induce both a proliferative response and
      neovascularization in bronchial mucosa. The projection of capillary loops into
      the bronchial mucosa also may be a result of neovascularization occurring within
      the lamina propria of the bronchial wall.

PMID- 12237924
TI  - Small-volume image-guided radiotherapy using hypofractionated, coplanar, and
      noncoplanar multiple fields for patients with inoperable Stage I nonsmall cell
      lung carcinomas.
AB  - BACKGROUND: Occasionally, medically compromised and/or elderly patients with
      nonsmall cell lung carcinomas (NSCLCs) cannot be treated surgically. We
      investigated small-volume hypofractionated image-guided radiotherapy (IGRT)
      without the need for breath control in patients with inoperable Stage I NSCLCs.
      METHODS: Between September 1996 and September 1999, 22 patients with Stage I
      NSCLCs, including 19 males and 3 females, were treated with IGRT. Among these
      patients, there were 13 Stage IA and 9 Stage IB tumors. The tumors ranged in size
      from 14.2 to 58.5 mm, with a median size of 26.7 mm. Of the 22 patients, 19 were
      unfit for surgical treatment due to poor pulmonary function, complications,
      and/or advanced age and 3 refused surgery. Computed tomographic scans (CT) of the
      primary tumor were taken during three respiratory phases and they were analyzed
      to determine the planning target volume, which included only the primary tumor
      with allowances for respiratory movement. The radiation doses administered at the
      edge of the moving tumor during normal breathing were 80% of the prescribed dose,
      either 48 or 60 Gy given in eight fractions over 2 weeks. Clinical evaluation,
      chest CT scan, and pulmonary function tests were performed before irradiation and
      at regular intervals for the post-IGRT follow-up. The median follow-up period was
      24 months (range, 2-44 months; mean, 21.8 months) (at least 24 months for
      survivors). RESULTS: Of 17 tumors assessed at the initial follow-up 2-6 months
      after treatment (5 complete responses, 11 partial responses, and 1 progressive
      disease), 16 (94%) were controlled locally. One local recurrence was observed
      during the follow-up. The lung carcinoma-specific survival rate at 1 year was 94%
      and the 1-year actuarial recurrence-free survival rate was 71%. The lung
      carcinoma-specific survival rate at 2 years was 73% and the 2-year actuarial
      recurrence-free survival rate was 67%. The treatment was well tolerated and no
      major side effects were observed. Localized radiation pneumonitis was observed in
      all patients who were examined by CT scan, but the patients were asymptomatic.
      Parameters of pulmonary function, including vital capacity, total lung capacity,
      and diffusion capacity for carbon monoxide, decreased very little or not at all,
      indicating that IGRT rarely deteriorated pulmonary functions. CONCLUSIONS: Small
      volume hypofractionated IGRT without breath control is a feasible and beneficial
      method for the curative treatment of patients with Stage I NSCLCs. It has the
      potential of a high local tumor control rate and low morbidity.

PMID- 12237925
TI  - Strategies for improving melanoma education and screening for men age >or= 50
      years: findings from the American Academy of Dermatological National Skin Cancer
      Sreening Program.
AB  - BACKGROUND: Recently, the Institute of Medicine (2000) and the Third United
      States Preventive Services Task Force (2001) called for studies to help
      clinicians identify patients, especially elderly patients, who are at high risk
      for melanoma. In the current study, the authors sought to identify factors
      associated with a high yield in skin cancer screening and to explore strategies
      for improving mass screenings for melanoma. METHODS: The authors analyzed the
      data base of the 242,374 skin cancer screenings conducted on more than 206,000
      Americans who attended the American Academy of Dermatology National Skin Cancer
      Screening Programs during the period 1992-1994. RESULTS: Ninety-six percent of
      3476 screenees with a presumptive diagnosis of melanoma or possible melanoma were
      contacted, and follow-up records were obtained for 73% of screenees. Of these,
      363 screenees had histologically proven melanoma. Middle-aged and older men (age
      >or= 50 years) comprised only 25% of screenees but comprised 44% of those with a
      confirmed diagnosis of melanoma. The overall yield of melanoma (the number of
      confirmed diagnoses per the number of screenees) was 1.5 per 1000 screenings (363
      diagnoses of 242,374 screenees) compared with a yield of 2.6 per 1000 screenings
      among men age >or= 50 years. The yield was improved further for men age >or= 50
      years who reported either a changing mole (4.6 per 1000 screenings) or skin types
      I and II (3.8 per 1000 screenings). The predictive value of a screening diagnosis
      of melanoma was more than twice as high for men age >or= 50 years with either a
      changing mole or skin types I and II compared with all other participants.
      CONCLUSIONS: The yield of mass screening for melanoma would be improved by
      outreach to middle-aged and older men, with particular focus on men with changing
      moles or with skin types I and II. Primary care physicians should be attuned to
      the risk factors among all of their patients but should be alerted in particular
      to the heightened risk of melanoma for men age >or= 50 years. Formal assessment
      of the impact of targeted screening on mortality warrants further study.

PMID- 12237926
TI  - Thin primary cutaneous melanomas: associated detection patterns, lesion
      characteristics, and patient characteristics.
AB  - BACKGROUND: Public awareness and education may lead to the detection of thinner
      melanomas, which may result in a decrease in morbidity and mortality rates. Which
      detection patterns, lesion, and patient characteristics are associated with early
      detection? METHODS: Using the University of Michigan prospective melanoma
      database, the detection patterns, lesion characteristics, and patient
      characteristics of 1515 consecutive patients with in situ or invasive cutaneous
      melanomas were reviewed. Tumor thickness (measured in millimeters) was evaluated
      in relationship to detection patterns (patient, physician, spouse), lesion
      characteristics (change in color, size, shape/elevation, ulceration, bleeding,
      tenderness, itching), and patient characteristics (gender, skin type, number of
      atypical and clinically benign nevi, history of sunburn, personal and family
      history of melanoma). RESULTS: Patient characteristics associated with early
      detection included female gender, at least one atypical nevus, greater than 20
      clinically benign nevi, and/or a personal history of melanoma. Skin types I, II,
      and III, a history of sunburn, and/or a family history of melanoma were also
      associated with thinner lesions, but these associations were not statistically
      significant. Lesion characteristics associated with earlier detection included a
      change in color, size, shape/elevation, and/or itching. Physician-detected
      melanomas were significantly thinner than patient or spouse-detected lesions.
      CONCLUSIONS: Educational campaigns should include increasing melanoma awareness
      in males and educating the public on the early signs and symptoms. Education
      should be directed at both high and low-risk groups. Physicians should consider
      performing total skin examinations routinely on patients. Although they detect a
      relatively small percentage of all melanomas, physicians detect significantly
      thinner lesions.

PMID- 12237927
TI  - Characterization of 11 human sarcoma cell strains: evaluation of cytogenetics,
      tumorigenicity, metastasis, and production of angiogenic factors.
AB  - BACKGROUND: Human sarcomas have a propensity for aggressive local invasion and
      early pulmonary metastasis. Frequently, deaths are due to uncontrolled pulmonary
      metastases. The purpose of the current study was to evaluate cytogenetics,
      tumorigenicity, metastatic potential, and production of angiogenic factors in
      human sarcoma cell strains. A secondary purpose was to establish low passage cell
      strains for studying new therapeutic approaches. METHODS: The authors established
      11 cell strains from human sarcoma surgical specimens and characterized their in
      vitro tumor properties, including growth in soft agar, expression of angiogenic
      growth factors (vascular endothelial growth factor [VEGF] and basic-fibroblast
      growth factor [bFGF]), and cytogenetics. RESULTS: All of the cell strains
      remained diploid. All exhibited the ability to grow in soft agar and expressed
      both VEGF as well as bFGF. In addition, 6 of the 11 established sarcoma cell
      strains were tumorigenic, 5 of which spontaneously metastasized to the lungs in
      nude mice. Four of the five cell strains that yielded lung metastases were
      derived from lung metastases in patients. CONCLUSIONS: The 11 cell strains, which
      were derived from diverse sarcoma histologies, will provide a model for studying
      not only metastatic progression but also the in vitro and in vivo efficacy of new
      therapeutic modalities for human sarcomas.

PMID- 12237928
TI  - Barriers and facilitators to enrollment in cancer clinical trials: qualitative
      study of the perspectives of clinical research associates.
AB  - BACKGROUND: The literature continues to report low rates of accrual to cancer
      clinical trials. Previous studies have examined principally physician-related or
      patient-related barriers. Clinical research associates (CRAs) have a unique
      perspective on enrollment that has been explored very little. This study sought
      the views of CRAs on barriers and facilitators to accrual. METHODS: Focus groups
      were held at six of eight tertiary cancer centers in Ontario, Canada. Audiotapes
      of sessions were transcribed and subjected to content analysis by two of the
      authors. Emergent themes were identified. These themes are illustrated by
      representative quotes taken from the transcripts. RESULTS: Factors that acted as
      barriers or facilitators were classified into physician-related, patient-related,
      or system-related factors. CRAs identified physician attitudes regarding patient
      participation as the principal physician-related barrier. Barriers, facilitators,
      and modifying factors that were related to patient involvement were discussed by
      CRAs. Patients seemed more knowledgeable about trials than in the past and were
      willing to participate. System factors were considered to have the greatest
      impact on the ability to accrue. CRAs identified increasing trial and
      pharmaceutical demands coupled with tight trial time lines. Time was seen as a
      diminishing resource. Greater demands not only affect specific clinical trial
      accrual but also affect general support for trials in the cancer center and
      hospital. CONCLUSIONS: The impact of greater demands in a climate of decreasing
      health care resources is perceived by CRAs as having a negative affect on
      accrual. Consequently, the important process of translating potentially
      beneficial basic research findings into clinical practice is slowed.

PMID- 12237929
TI  - Factors that influence the recruitment of patients to Phase III studies in
      oncology: the perspective of the clinical research associate.
AB  - BACKGROUND: The multiple determinants of a patient's decision to enter into a
      clinical trial have been explored largely from the perspectives of patients and
      their physicians. Little research has involved clinical research associates
      (CRAs) formally, despite their central role in the process of recruitment. The
      current study was initiated to explore the factors that influence the decision of
      patients with cancer regarding clinical trial entry, specifically from the
      perspective of the CRA. METHODS: Two focus groups of CRAs from the Hamilton
      Regional Cancer Center were organized. A skilled facilitator guided both groups
      through exploratory and subsequent confirmatory phases of discussions, which were
      audiotaped for review and coding using a process of consensus employing
      intercoder triangulation. RESULTS: The two groups identified a number of factors
      that they believed influenced the recruitment process. Numerous physician and
      patient factors were reaffirmed, such as the impression of the scientific merit
      of a study or the sense of personal benefit, respectively. More uniquely, CRAs
      identified information transfer within the informed consent process as a major
      aspect of their specialized role. It was believed that full disclosure of
      information, in terms of both the content and the techniques and styles of
      delivery, was an important predictor of recruitment success. The groups quickly
      reached consensus on which factors they believed were the most important overall
      with respect to influencing study recruitment. CONCLUSIONS: CRAs appear to have a
      unique role in the process of recruiting patients to active clinical trials. They
      believe that they have an important influence on recruitment success. Further
      research to validate this impression is required, because, ultimately, a greater
      understanding of the relative roles of physician and patient factors and,
      potentially, CRA factors will be important in the development of ethical and
      supportive strategies to optimize the recruitment of patients with cancer into
      randomized clinical trials.

PMID- 12237930
TI  - Trastuzumab-associated cardiotoxicity.
AB  - Trastuzumab is a monoclonal antibody used for the treatment of metastatic breast
      carcinoma in women whose tumors overexpress the HER2 protein. Cardiotoxicity has
      been reported to occur with trastuzumab when administered alone and in
      combination with antineoplastic agents, particularly anthracyclines. The risk of
      cardiotoxicity with trastuzumab has been reported to be 4% with monotherapy and
      27% when administered in combination with an anthracycline and cyclophosphamide,
      but to the author's knowledge severe outcomes, such as death or permanent
      disability, are uncommon. The majority of reported cardiac effects are mild to
      moderate, nonspecific, and medically manageable. Signs and symptoms are similar
      to those observed in patients who develop anthracycline-induced cardiomyopathy
      and include tachycardia, palpitations, and exertional dyspnea, which may progress
      to congestive heart failure. The pathogenesis and histologic changes responsible
      for trastuzumab-associated cardiotoxicity currently are under investigation.
      Unlike anthracycline-induced toxicity, trastuzumab-associated toxicity usually
      responds to standard treatment or the discontinuation of trastuzumab, and there
      is no evidence that the toxicity is dose related. Current methods for the early
      detection of cardiotoxicity in trastuzumab-treated patients are similar to those
      used in anthracycline-treated patients. Cardiac function is established at
      baseline and monitored regularly during treatment by physical examination and
      measurement of left ventricular ejection fraction. The majority of patients
      improve with proper treatment, and some are able to continue to receive
      trastuzumab.

PMID- 12237931
TI  - Must patients with advanced cancer choose between a Phase I trial and hospice?
AB  - BACKGROUND: Phase I oncology trials offer no meaningful chance for direct medical
      benefit and they may prevent patients with advanced cancer from receiving
      palliative care in a hospice program. However, it is not known whether dual
      enrollment in a Phase I trial and hospice is feasible. METHODS: Five hundred
      thirty-four Phase I trials were identified in a national online database, of
      which 179 (34%) accepted patients with a life expectancy of less than 6 months.
      Of these, 50 were selected randomly. Their principal investigators were surveyed
      by fax, with follow-up telephone calls and e-mails. Ninety-two hospices were
      selected randomly from a national database. Surveys were conducted by telephone
      with intake coordinators. Principal investigators were asked whether patients
      enrolled in hospice could also enroll in their trials if they were eligible in
      all other respects. Hospice intake coordinators were asked whether a patient with
      advanced cancer who met hospice eligibility criteria could also enroll in a Phase
      I trial. RESULTS: Surveys were completed by 45 of 50 principal investigators
      (90%) and by 89 of 92 hospices (97%). Although both groups were in favor of dual
      enrollment, principal investigators (41 of 45; 91%) were more likely to support
      dual enrollment than hospices (60 of 89; 67%; chi-square test, P = 0.004). Most
      hospices that did not support dual enrollment cited reasons that were based on
      concerns about payment or misunderstandings about the nature of Phase I trials.
      CONCLUSIONS: Most hospices and Phase I principal investigators believe that
      eligible patients should be allowed to enroll simultaneously in hospice and Phase
      I trials. These results suggest that the choice between hospice and a Phase I
      trial is a false dilemma and that greater collaboration in this area is needed.

PMID- 12237932
TI  - The role of extreme phenotype selection studies in the identification of
      clinically relevant genotypes in cancer research.
AB  - The investigation of genetic alterations that may be related to the prognosis of
      patients with malignant disease has become a frequently used strategy in recent
      years. Although some conclusions have been reached in certain studies, the
      complexity and the multifactorial nature of most neoplastic diseases makes it
      difficult to identify clinically relevant information, and the results of some
      studies have been of borderline significance or have been conflicting. In
      contrast, the identification and the study of patients or families with very
      characteristic phenotypes have yielded outstanding results in the identification
      of the genetic characteristics underlying such phenotypes. Although, in most
      cases, the individuals who are selected for these types of studies are
      characterized by a negative phenotype (i.e., individuals who are at increased
      risk for developing a specific disease), a few studies have been directed toward
      individuals with phenotypes that imply an unusually good prognosis (i.e.,
      individuals who present with a decreased risk for developing specific diseases
      despite an important exposure to well-known risk factors). Therefore, it seems
      logical to develop this strategy further as a valid methodology for the study of
      other diseases, such as cancer. The study of individuals with phenotypes that
      imply an extremely good prognosis, such as long-term survivors of theoretically
      incurable malignancies or individuals who seem to be protected against a certain
      neoplastic disorder despite having a markedly increased risk for its development,
      may unveil genetic alterations that explain such characteristic phenotypes and
      may provide potentially useful therapeutic targets against these diseases.

PMID- 12237933
TI  - The Maka femur and its bearing on the antiquity of human walking: applying
      contemporary concepts of morphogenesis to the human fossil record.
AB  - MAK-VP-1/1, a proximal femur recovered from the Maka Sands (ca. 3.4 mya) of the
      Middle Awash, Ethiopia, and attributed to Australopithecus afarensis, is
      described in detail. It represents the oldest skeletal evidence of locomotion in
      this species, and is analyzed from a morphogenetic perspective. X-ray, CT, and
      metric data are evaluated, using a variety of methods including discriminant
      function. The specimen indicates that the hip joint of A. afarensis was
      remarkably like that of modern humans, and that the dramatic muscle allocation
      shifts which distinguish living humans and African apes were already present in a
      highly derived form in this species. Its anatomy provides no indication of any
      form of locomotion save habitual terrestrial bipedality, which very probably
      differed only trivially from that of modern humans.

PMID- 12237934
TI  - Paleodemographic comparison of a catastrophic and an attritional death
      assemblage.
AB  - The aim of this contribution is to examine the effect of an indiscriminate
      epidemic on a population to assess whether or not a catastrophic event can be
      identified from examination of paleodemographic data. Using paleodemographic
      techniques, the death assemblage from the Royal Mint site, London, a Black Death
      cemetery dated 1349 AD, is compared with that from St. Helen-on-the-Walls, York,
      which dates from the twelfth to the sixteenth centuries AD. The Royal Mint site
      represents a catastrophic cemetery, while that of St. Helen-on-the-Walls is of an
      attritional type. Certain features of the paleodemographic profile of the plague
      victims suggest that the population had been affected by factors other than
      natural wastage. Three factors are proposed which may define an indiscriminate
      catastrophic event in preindustrial populations.

PMID- 12237935
TI  - Mandibular condyle traits in Neanderthals and other Homo: a comparative,
      correlative, and ontogenetic study.
AB  - The relationship between the mandibular condyle and the crest of the mandibular
      notch (CMN) has historically entered into discussions of Neanderthal
      characteristics and was recently suggested to be autapomorphic in Neanderthals.
      The Neanderthal CMN has been described as intersecting the condyle in the middle,
      while the modern human CMN runs to the condyle's lateral end. A large lateral
      condylar tubercle (LCT) has also been observed in Neanderthals and thought to be
      related to medial (or less lateral) CMN position. In addition, the presence of a
      less lateral CMN early in ontogeny, as seen in the Amud 7 infant, has been argued
      to demonstrate great evolutionary divergence in Neanderthals. Using a scoring
      system for each trait, this study first examines the expression of CMN position
      and LCT size in 102 adult modern humans and in samples of Neanderthals and other
      fossil Homo. Then, CMN position is scored in 208 subadult modern humans to
      elucidate the ontogeny of this trait. Results show that CMN position is not
      autapomorphic in Neanderthals, but Neanderthals have significantly more CMNs in
      the least-lateral score category than does the modern human sample. Large LCTs
      are found to be strongly predictive of less lateral CMN position, although less
      lateral CMN position may exist in the absence of a large LCT. The complex
      ontogenetic pattern of CMN expression observed indicates that features of
      subadult and adult condylar morphology cannot be constructively compared without
      first considering subadult morphology on its own functional and developmental
      terms.

PMID- 12237936
TI  - Asymmetrical spondylolysis.
AB  - The objective of this study was to examine examples of spondylolysis in which the
      pattern of separation was clearly asymmetrical, in order to learn more about the
      process of bone separation that produces this condition. Although the primary
      focus was on unilateral complete separation, examples of asymmetry represented by
      incomplete separation and by complete bilateral separation where the separation
      sites are in different locations on the two sides were included. Two collections
      were used, one consisting of Canadian Inuit skeletons curated at the Canadian
      Museum of Civilization, and the other of 48 individual examples of asymmetrical
      spondylolysis from sites in a variety of localities curated by several different
      institutions. The first collection was studied primarily to observe early
      manifestations of spondylolysis, particularly incomplete separation, while
      various patterns of asymmetrical complete separation were the focus of the
      second. The results indicate that asymmetry is part of the earliest osteological
      picture of spondylolysis, with right-sidedness predominating, a condition perhaps
      related in some way to handedness. The right-side predominance appears to
      decrease with age. The ratio of unilateral to bilateral separation ranges from 3
      33% in different studies, and a significant number of the unilateral separations
      have spina bifida occurring in the same vertebra. Overall, the specimens examined
      here, considered along with clinical cases, nicely illustrate a progression of
      spondylolysis. A unilateral separation may heal, it may progress to bilateral
      separation, or it may remain as a permanent condition, producing a pattern of
      degenerative changes that can include spondylolisthesis. A unilateral healing of
      bilateral complete separation is likely a rare phenomenon, at least after the
      separations have reached a certain level of maturity.

PMID- 12237937
TI  - Genetic substructure in South African Bantu-speakers: evidence from autosomal DNA
      and Y-chromosome studies.
AB  - The extent of genetic differentiation between seven South African Bantu-speaking
      groups (Zulu, Xhosa, Tsonga/Shangaan, Southern Sotho, Pedi, Tswana, and Venda)
      was assessed from coancestry coefficients (F(ST)) estimated from autosomal
      serogenetic, DNA, and Y-chromosome DNA haplotypes. The overall F(ST) obtained
      from the autosomal data was 0.002, and that from the Y chromosome data was 0.014.
      The genetic relationships between groups examined were inferred from their
      cluster affinities in phylogenetic trees constructed from the genetic distances
      between them. Both autosomal and Y-chromosome DNA studies reveal that 6 of the 7
      South African Bantu-speaking groups cluster according to their linguistic
      groupings, the exception being the Tsonga, who do not cluster with other Nguni
      language speakers, but rather with the Venda who live close to them. This
      suggests that the invading Shangaan-speakers, whose Nguni language was adopted by
      the Tsonga, did not have a major effect on the Tsonga gene pool, and that gene
      flow from the Venda into the Tsonga may have been considerable. Genetic distances
      were found to correlate with geographic distances between the regions where each
      group's apparent population density is the highest. Linguistic distances were
      also found to correlate with genetic distances, but linguistic and geographic
      distances showed no correlation. Together, these results suggest that linguistic
      and some genetic differentiation took place before the groups (or their
      forerunners) reached their present-day locations, and that further genetic change
      occurred after their arrival.

PMID- 12237938
TI  - New tool use by wild Sumatran orangutans (Pongo pygmaeus abelii).
AB  - Two forms of tool use by wild Sumatran orangutans are reported from the Agusan
      Monitoring Station, a new research site in Indonesia. One form, a branch "hook"
      used in locomotion, has not been reported previously in wild orangutans. The
      second form, a leaf "pad" used to protect the hands and feet from thorns while
      feeding, shares similarities in form and function with a tool type used by
      orangutans at Ketambe, a nearby research site. Both instances of tool use
      occurred in areas of disturbance, and appear to be spontaneous inventions under
      novel conditions, although habitual use of the tool in other ecological contexts
      is plausible. A summary of the distribution of tool use types in wild orangutans
      is presented.

PMID- 12237939
TI  - A blind test of mandibular morphology for sexing mandibles in the first few years
      of life.
AB  - Loth and Henneberg ([2001] Am. J. Phys. Anthropol. 115:179-186) proposed that
      consistent shape differences exist between male and female juvenile mandibles
      which can be used to predict sex with an accuracy of 81%. A sample of known sex
      and age from the Spitalfields Collection was examined blind twice and resulted in
      an overall accuracy of only 64%. The tests also showed that: 1) the method sexed
      males more reliably than females; and 2) consistency was low.

PMID- 12237940
TI  - Revised age estimates of Australopithecus-bearing deposits at Sterkfontein, South
      Africa.
AB  - The Sterkfontein fossil site in South Africa has produced the largest
      concentration of early hominin fossils from a single locality. Recent reports
      suggest that Australopithecus from this site is found within a broad
      paleontological age of between 2.5-3.5 Ma (Partridge [2000] The Cenozoic of
      Southern Africa, Oxford: Oxford Monographs, p. 100-125; Partridge et al. [2000a],
      The Cenozoic of Southern Africa, Oxford: Oxford Monographs, p. 129-130; Kuman and
      Clarke [2000] J Hum Evol 38:827-847). Specifically, the hominin fossil commonly
      referred to as the "Little Foot" skeleton from Member 2, which is arguably the
      most complete early hominin skeleton yet discovered, has been
      magnetostratigraphically dated to 3.30-3.33 Ma (Partridge [2000] The Cenozoic of
      Southern Africa, Oxford: Oxford Monographs, p. 100-125; Partridge et al. [2000a],
      The Cenozoic of Southern Africa, Oxford: Oxford Monographs, p. 129-130). More
      recent claims suggest that hominin fossils from the Jacovec Cavern are even
      older, being dated to approximately 3.5 Ma. Our interpretation of the fauna, the
      archeometric results, and the magnetostratigraphy of Sterkfontein indicate that
      it is unlikely that any Members yet described from Sterkfontein are in excess of
      3.04 Ma in age. We estimate that Member 2, including the Little Foot skeleton, is
      younger than 3.0 Ma, and that Member 4, previously dated to between 2.4-2.8 Ma,
      is more likely to fall between 1.5-2.5 Ma. Our results suggest that
      Australopithecus africanus should not be considered as a temporal contemporary of
      Australopithecus afarensis, Australopithecus bahrelghazali, and Kenyanthropus
      platyops.

PMID- 12237941
TI  - Genomic imprinting and epigenetic reprogramming: unearthing the garden of forking
      paths.
AB  - Genomic imprinting, an epigenetic form of gene regulation, determines the parent
      dependent gene expression of marked or imprinted genes during gametogenesis and
      embryonic development. Imprinting involves differential allele DNA methylation in
      one sex cell lineage but not in the other. Egg and sperm each contributes the
      same DNA sequences to the zygote but epigenetic imprinting of a subset of genes
      determines that only one of the parent alleles are expressed relative to the
      parental origin. Primordial germ cells inherit biallelically imprinted genes from
      maternal and paternal origin and erase their imprints to start de novo
      monoallelic imprinting during gametogenesis. Epigenetic paternalization is an
      ongoing process in the mitotically-dividing spermatogonial stem cell and derived
      meiotically-dividing spermatocyte progeny to endow sperm with imprinted alleles.
      Epigenetic maternalization is restricted to the oocyte growth phase of
      folliculogenesis and is unrelated to DNA replication since it takes place while
      the oocyte remains in the diplotene stage of meiotic prophase I. Sperm and oocyte
      genomic methylation patterns depend on the activity of DNA methyltransferases
      (Dnmt). A variant of Dnmt1, designated Dnmt1o, accumulates in oocyte nuclei
      during the follicular growth phase. Dnmt3L, an isoform of Dnmt3a and Dnmt3b, but
      lacking enzymatic activity, interacts with Dnmt2a and Dnmt3b and is required for
      spermatogenesis. In the mouse early zygote, the male pronucleus is demethylated
      within 4 h of fertilization. Global demethylation takes place gradually up to the
      morula stage. In the blastocyst, de novo methylation is reestablished in the
      inner cell mass but not in the trophectoderm. Both the significance of genomic
      imprinting and the severe developmental defects caused by disrupted Dnmt
      activity, point to a need for a better understanding of the causes of low cloning
      efficiency by somatic nuclear transfer to enucleated ovulated oocyte.

PMID- 12237942
TI  - Expression of gelatinases and their tissue inhibitors in rat corpus luteum during
      pregnancy and postpartum.
AB  - Extensive tissue remodeling occurs in the corpus luteum (CL) during both
      formation and luteolysis. Matrix metalloproteinases (MMPs) and their tissue
      inhibitors (TIMPs) are believed to play pivotal roles in these processes. In the
      present study, to evaluate the potential roles of matrix degrading proteases in
      luteal development and regression, we examined gelatinases and TIMP-1, -2, -3
      mRNA expressions, as well as gelatinase activity in rat CL during pregnancy and
      postpartum using Northern blot, in situ hybridization, and gelatin zymography,
      respectively. The results showed that MMP-2 mRNA was only expressed at the early
      stages of pregnancy; TIMP-2 mRNA was highly expressed at the early and late
      pregnancy and day 1 postpartum, but could not be detected during the mid-phase of
      pregnancy; TIMP-3 mRNA expression was abundant during early pregnancy and peaked
      at day 7, but was absent from other time points examined. MMP-9 and TIMP-1 mRNAs
      in rat CL were below detectable level in the current study. Furthermore, the
      active MMP-2 was only present during the early stages of pregnancy, and no MMP-9
      activity was observed in the zymogram. Taken together, our results suggest that
      MMP-2 and TIMP-3 may have functional roles in rat luteal formation, while TIMP-2
      may be implicated in both formation and regression of the pregnant CL.

PMID- 12237943
TI  - Stimulation of the murine type II transforming growth factor-beta receptor
      promoter by the transcription factor Egr-1.
AB  - Previous studies have demonstrated that differentiation of murine embryonal
      carcinoma (EC) cells leads to the appearance of high affinity receptors for
      transforming growth factor-beta (TGF-beta). Subsequently, it was demonstrated
      that differentiation of F9 EC cells leads to increases in the transcription of
      the type II TGF-beta-receptor gene (TbetaR-II) and leads to significant increases
      in the steady-state levels of TbetaR-II mRNA. Analysis of the human TbetaR-II
      promoter in F9-differentiated cells identified several cis-regulatory elements
      that influence the activity of the promoter, including a CRE/ATF site and a CCAAT
      box motif. In the work described in this report, we focused on the effect of the
      transcription factor Egr-1 on the murine TbetaR-II promoter. We have identified
      an Egr-1 response-element approximately 150 bp upstream of the major
      transcription start site of the murine TbetaR-II gene. We demonstrate by
      electrophoretic mobility shift analysis (EMSA) that this cis-regulatory element
      binds Egr-1, and we demonstrate that disruption of this site eliminates the
      response to Egr-1. As part of this analysis, we also examined the effect of Egr-1
      on human TbetaR-II promoter. In contrast to a previous report, which reported
      that Egr-1 inhibits expression of human TbetaR-II promoter/reporter gene
      constructs, we did not observe an inhibitory effect of Egr-1 that was specific
      for the human TbetaR-II promoter. Taken together, the findings described in this
      report identify important differences between the human and the murine TbetaR-II
      promoter, and our findings identify an Egr-1 cis-regulatory element that is
      capable of stimulating the activity of the murine TbetaR-II promoter.

PMID- 12237944
TI  - TACC3 expression and localization in the murine egg and ovary.
AB  - A protein spot cored from a silver-stained two dimensional (2D) gel of germinal
      vesicle stage immature mouse oocytes was identified as Transforming Acidic Coiled
      Coil containing protein (TACC3) by tandem mass spectrometry. PCR amplification
      revealed two alternatively spliced forms, Tacc3a and Tacc3b, in mouse ovarian
      cDNA libraries. TACC3a encoded a 630 aa protein with a predicted mass of 70 kDa.
      It contained seven 24 aa repeats at the N-terminus and two coiled-coil domains at
      the C-terminus. TACC3b encoded a 426 aa protein with a predicted mass of 49 kDa
      also containing two coiled coil domains, but lacking the 168 aa repeat region. In
      addition to homology to the TACC family members, murine TACC3 also showed 35.7%
      identity to the Xenopus protein, Maskin, a cytoplasmic polyadenylation element
      binding protein (CPEB)-associated factor. Northern blot analysis demonstrated
      that TACC3a is abundantly expressed in adult testis and spleen and is moderately
      expressed in the ovary, heart, and lung, suggesting a wide tissue distribution.
      Both myc-tagged TACC3a and TACC3b targeted to the cytoplasm of transiently
      transfected CV-1 cells. In situ hybridization of mouse ovarian tissue sections
      displayed abundant expression of TACC3 specifically in the cytoplasm of growing
      oocytes, but not in primordial or atretic follicles. This pattern of expression
      suggests that TACC3 is expressed in ovarian cells undergoing active growth and
      development.

PMID- 12237945
TI  - Expression and characterization of functional recombinant bovine follicle
      stimulating hormone (boFSHalpha/beta) produced in the milk of transgenic rabbits.
AB  - Bovine follicle-stimulating hormone (boFSH) is a heterodimeric glycoprotein that
      belongs to the pituitary gonadotropins. Bioactive FSH is composed of alpha and
      beta subunits which require extensive N-glycosylation and sialylation. The
      mammary gland of transgenic livestock is an attractive source for the synthesis
      of post-translationally modified proteins. Two mammary gland-specific gene
      constructs with the cDNA for the boFSH alpha (boFSHalpha) and beta (boFSHbeta)
      subunits controlled by bovine alpha-s1 casein regulatory sequences were co
      microinjected into fertilized rabbit oocytes. Two FSHalpha/FSHbeta double
      transgenic rabbit lines were established. The transgene expression was strictly
      lactation and mammary gland specific. Protein analysis revealed the presence of
      the boFSH heterodimer in the milk of transgenic rabbits showing a molecular
      weight similar to that of purified pituitary gland derived boFSH (boFSH-P).
      Subunit specific antibodies detected both polypeptides with the expected
      molecular sizes. Biochemical characterization demonstrated the expected
      isoelectric points of the recombinant boFSH. The presence of the post
      translationally added terminal sialic acid residues was indicated by wheat germ
      agglutinin (WGA) lectin Western blotting. The biological activity of the
      recombinant mammary gland produced boFSH was determined using a FSH-dependent
      reporter cell line. The bioactivity of the recombinant boFSH was comparable to
      that of purified boFSH-P.

PMID- 12237946
TI  - Transfection of embryonal carcinoma cells at high efficiency using liposome
      mediated transfection.
AB  - Embryonal carcinoma (EC) cells are recognized as an excellent model system for
      studying the early stages of mammalian development. Many studies performed with
      EC cells involve transient transfection with promoter/reporter gene constructs
      and/or mammalian expression vectors. One of the limitations of working with EC
      cells is their inability to be transfected at high efficiency. In most cases, EC
      cells are transfected using the calcium phosphate method. The objective of this
      study was to identify protocols and culture conditions that significantly
      increase the transfection efficiency of EC cells. F9 EC cells were used for this
      purpose, because they are the EC cell line studied most commonly. We show that
      the transfection efficiency of F9 EC cells using the calcium phosphate method is
      less than 5%; whereas, their transfection efficiency can be improved
      approximately 15-fold using optimized culture conditions and liposome-based
      transfection reagents. Specifically, we demonstrate that more than 50% of F9 EC
      cells can be transfected using LipofectAMINE 2000. In addition to higher levels
      of transfection, there is much less plate-to-plate variation with liposome-based
      reagents as compared to transfection with calcium phosphate. Interestingly,
      transfection efficiency using these reagents was found to be inversely related to
      cell density. This contrasts sharply with the recommendation that transfection
      with LipofectAMINE 2000 or LipofectAMINE in conjunction with the PLUS reagent be
      performed at high cell densities. Given the improvements in transfection
      efficiency reported here, it will now be possible to perform studies with F9 EC
      cells that require transfection at significantly higher levels than that achieved
      using the calcium phosphate method. Overall, the highest transfection
      efficiencies were consistently obtained using LipofectAMINE 2000.

PMID- 12237947
TI  - Growth, development, and gene expression by in vivo- and in vitro-produced day 7
      and 16 bovine embryos.
AB  - The effects of the embryo production system on growth and transcription rate of
      day 7 and 16 bovine embryos were investigated. In vivo- (controls) and in vitro
      produced (IVP) embryos were transferred to female recipients on day 7 of
      development, and were allowed to develop in a synchronous uterine environment to
      day 16. Embryonic transcripts for insulin-like growth factors-1 and -2 (IGF-1 and
      -2), their receptors (IGF-1r and -2r), facilitative glucose transporters-1 and -3
      (Glut-1 and -3), and interferon-tau (IFN-tau) were determined by real-time
      quantitative PCR (TaqMan); gender diagnosis was performed on day 16 concepti
      only. On day 7, IVP embryos presented lower mRNA levels than controls (P < 0.05),
      but these differences were generally reduced on day 16. No IGF-1 transcripts were
      detected on day 7, but a low IGF-1 mRNA level was observed in day 16 embryos. In
      the IVP group, IFN-tau mRNA levels were lower on day 7 (P < 0.05), but higher
      than controls on day 16 (P < 0.05). Control embryos showed a temporal decrease in
      the relative transcription from day 7 to 16 (P < 0.05), except IGF-1 mRNA. On day
      16, IVP concepti were shorter and displayed smaller embryonic discs (P < 0.05).
      Female concepti were generally smaller than males, and IGF-2r mRNA and growth
      were negatively correlated. The in vitro production of bovine embryos negatively
      affected the amount of gene expression on day 7 and the rate of development on
      day 16. Physical traits and transcriptional activity on day 16 were associated
      with one another, which appeared to be significant for growth and development.

PMID- 12237948
TI  - Aberrant methylation patterns at the two-cell stage as an indicator of early
      developmental failure.
AB  - The fertilized mouse egg actively demethylates the paternal genome within a few
      hours after fertilization, whereas the maternal genome is only passively
      demethylated by a replication-dependent mechanism after the two-cell stage. This
      evolutionarily conserved assymetry in the early diploid mammalian embryo may have
      a role in methylation reprogramming of the two very different sets of sperm and
      egg chromatin for somatic development and formation of totipotent cells.
      Immunofluorescence staining with an antibody against 5-methylcytosine (MeC)
      showed that the incidence of abnormal methylation patterns differs between mouse
      two-cell embryos from superovulated females, nonsuperovulated matings, and in
      vitro fertilization (IVF). It also depends on embryo culture conditions and
      genetic background. In general, there was a good correlation with the number of
      embryos (from the same experiment) which did not develop in vitro up to the
      blastocyst stage. Thus, aberrant genome-wide DNA methylation in early embryos may
      be an important mechanism contributing to the high incidence of developmental
      failure in mammals. Similar to the situation in abnormally methylated embryos
      from nuclear transfer, it may cause a high incidence of pregnancy loss and
      abnormal phenotypes.

PMID- 12237949
TI  - Developmental changes in inhibitory effects of arsenic and heat shock on growth
      of pre-implantation bovine embryos.
AB  - Although sensitive to various disrupters, pre-implantation embryos possess some
      cellular cytoprotective mechanisms that allow continued survival in the face of a
      deleterious environment. For stresses such as heat shock, embryonic resistance
      increases as development proceeds. Present objectives were to determine whether
      (1) arsenic compromises development of pre-implantation bovine embryos, (2)
      developmental changes in embryonic resistance to arsenic mimic those seen for
      resistance to heat shock, and (3) developmental patterns in induction of
      apoptosis by arsenic are correlated with similar changes in resistance of embryos
      to inhibitory effects of arsenic on development. Bovine embryos produced by in
      vitro fertilization were exposed at the two-cell stage or at day 5 after
      insemination (embryos > or = 16-cells in number) to either sodium arsenite (0, 1,
      5, or 10 microM) or heat shock (exposure to 41 degrees C for 0, 3, 4.5, 6, or 9
      hr). Arsenic induced apoptosis and increased group 2 caspase activity for embryos
      at the > or = 16-cell stage, but not for embryos at the two-cell stage. In
      contrast to these developmental changes in apoptosis responses, exposure to
      arsenic reduced cell number 24 hr after exposure for both two-cell embryos and
      embryos > or = 16-cells. Similarly, the percentage of embryos that developed to
      the blastocyst stage at day 8 after fertilization was reduced by arsenic exposure
      at both stages of development. Heat shock, conversely, reduced development to the
      blastocyst stage when applied at the two-cell stage, but not when applied to
      embryos > or = 16-cells at day 5 after insemination. In conclusion, arsenic can
      compromise development of bovine pre-implantation embryos, the temporal window of
      sensitivity of embryos to arsenic is wider than for heat shock, and cellular
      cytoprotective responses that embryos acquire for thermal resistance are not
      sufficient to cause increased embryonic resistance to arsenic exposure. It is
      likely that despite common cellular pathologies caused by arsenic and heat shock,
      arsenic acts to reduce development in part through biochemical pathways not
      activated by heat shock. Moreover, the embryo does not acquire significant
      resistance to these perturbations within the time frame in development examined.

PMID- 12237950
TI  - Lipovitellins and phosvitins of the fertilized eggs during embryo growth in the
      oviparous lizard Podarcis sicula.
AB  - In the lizard Podarcis sicula, the major vitellogenin (VTG)-derived yolk
      proteins, lipovitellins and phosvitins, were extracted from the yolk globules of
      laid and fertilized eggs at different periods of incubation up to 44 days close
      to hatching. Embryonic development was almost over at this time. Yolk proteins
      were isolated by precipitation in saturated (NH(4))(2)SO(4), separated on SDS
      PAGE and detected by Western blotting with homologous polyclonal anti/VTG
      antibody. Two lipovitellins of 110 and 116 kDa were always present in the yolk of
      laid eggs after 1, 10, 18, and 44 days from oviposition. Both these proteins were
      glycosylated and were recognized by the anti/VTG antibody; their N-terminal
      sequences were analyzed. Four phosvitins were detected in freshly laid eggs, but
      their number decreased during incubation, and after 44 days only a single protein
      of approximately 6.5 kDa was present. The results indicated that, in this lizard,
      during embryonic development, lipovitellins remain unchanged, whereas the
      phosphorylated components of yolk undergo continuous degradation.

PMID- 12237951
TI  - Vitellogenin precursors in the liver of the oviparous lizard, Podarcis sicula.
AB  - In reptiles, as in the other oviparous vertebrates, vitellogenin (VTG) synthesis
      is stimulated in the liver by ovarian estrogens. In this article, the presence of
      VTG precursors was detected in liver subcellular fractions of the oviparous
      lizard, Podarcis sicula, in the reproductive period. The rough endoplasmic
      reticulum (RER) and the smooth microsomal fraction (SMF), which includes smooth
      endoplasmic reticulum and Golgi complex, were separated by means of two different
      sucrose gradients. The successful separation was controlled at the electron
      microscope. The contents of the different compartments were extracted by means of
      n-octyl-beta-D-glucopiranoside detergent and subjected to SDS-PAGE. Western
      Blotting with homologous anti/VTG antibody revealed two immunoreactive proteins
      of about 84 and 70 kDa in the RER, and four proteins of about 180, 150, 60, 50
      kDa in the SMF; all these proteins appeared phosphorylated and glycosylated. The
      differences in the molecular weight of these VTG precursors are discussed.

PMID- 12237952
TI  - Histone H1-like protein and a testis-specific variant in the reproductive tracts
      of Octopus vulgaris.
AB  - In this study, we have identified a 28-kDa protein resembling the linker H1 in
      the testis and prostate of the reproductive system of Octopus vulgaris. This
      protein, OvH1, was partially purified by reverse phase high-pressure liquid
      chromatography (HPLC) of the perchloric acid extract from testis nuclei. It
      showed electrophoretic mobility, CD spectrum and amino acid composition highly
      comparable with those of the mammalian histone. Moreover, it was
      microheterogeneous, as resulted from prostate and testis HPLC and mass
      spectrometry analyses. Such analysis showed that in testis there are two H1
      subfractions, which do not appear in the prostate. Amino acid composition of the
      major testis specific variant (OvH1t) showed high similarity with rat testis
      specific H1t. The histone-like nature of OvH1 was confirmed by its ability to
      bind DNA as tested both by circular dichroism and protection of the nucleic acid
      toward deoxyribonuclease I activity. The circular dichroism spectra of Octopus
      DNA in the absence and presence of increasing amounts of the protein showed a
      dose-dependent effect, leading to a progressive compactness of the
      polynucleotide. OvH1/DNA complexes were also resistant to nuclease digestion. The
      presence of H1 in the testis and prostate of the reproductive system of Octopus
      is discussed in light of the fact that there is a similarity between its behavior
      and that of vertebrates.

PMID- 12237953
TI  - Valosine containing protein is a substrate of cAMP-activated boar sperm tyrosine
      kinase.
AB  - Previously we reported that treatment of boar sperm with cAMP-elevating drugs
      induces tyrosine phosphorylation of a triton-insoluble 93 kDa protein (p93). We
      have isolated p93 by preparative SDS electrophoresis and blotting from urea
      extracted boar sperm and identified it as a valosine containing protein (VCP) by
      mass spectrometry and microsequencing. With the use of antibodies to VCP and
      phosphotyrosine (pY) we found that both p93 and VCP are poorly extractable with
      triton and are solubilized in > 6 M urea. Furthermore, VCP and p93 overlap on one
      and two dimensional (1 and 2D) electrophoretic gels, supporting the identity of
      p93 as a tyrosine-phosphorylated population of VCP. According to
      immunofluorescence, VCP is localized along the entire sperm tail, in the
      posterior ring, distal equatorial segment, and postacrosome. In addition, 9-12%
      sperm contained VCP in the acrosome. The cAMP-elevating treatment did not alter
      VCP localization but induced tail tyrosine phosphorylation in 15% sperm cells. In
      those sperm, VCP and pY colocalized in connecting piece and posterior ring.

PMID- 12237954
TI  - Evidence that anandamide-signaling regulates human sperm functions required for
      fertilization.
AB  - Ejaculated mammalian sperm require several hours exposure to secretions in female
      reproductive tracts, or incubation in appropriate culture medium in vitro, before
      acquiring the capacity to fertilize eggs. Arachidonylethanolamide (AEA), also
      known as anandamide, is a novel lipid-signal molecule that is an endogenous
      agonist (endocannabinoid) for cannabinoid receptors. We now report that AEA is
      present in human seminal plasma, mid-cycle oviductal fluid, and follicular fluid
      analyzed by high-performance liquid chromatography/mass spectrometry. Sperm are
      sequentially exposed to these reproductive fluids as they move from the vagina to
      the site of fertilization in the oviduct. Specific binding of the potent
      cannabinoid agonist [(3)H]CP-55,940 to human sperm was saturable (K(D) 9.71 +/-
      1.04 nM), suggesting that they express cannabinoid receptors. R-methanandamide
      [AM-356], a potent and metabolically stable AEA analog, and (-)delta(9)
      tetrahydrocannabinol (THC), the major psychoactive constituent of Cannabis,
      modulated capacitation and fertilizing potential of human sperm in vitro. AM-356
      elicited biphasic effects on the incidence of hyperactivated sperm motility (HA)
      between 1 and 6 hr of incubation: at (2.5 nM) it inhibited HA, while at (0.25 nM)
      it stimulated HA. Both AM-356 and THC inhibited morphological alterations over
      acrosomal caps between 2 and 6 hr (IC(50) 5.9 +/- 0.6 pM and 3.5 +/- 1.5 nM,
      respectively). Sperm fertilizing capacity, measured in the Hemizona Assay, was
      reduced 50% by (1 nM) AM-356. These findings suggest that AEA-signaling may
      regulate sperm functions required for fertilization in human reproductive tracts,
      and imply that smoking of marijuana could impact these processes. This study has
      potential medical and public policy ramifications because of the incidence of
      marijuana abuse by adults in our society, previously documented reproductive
      effects of marijuana, and the ongoing debate about medicinal use of marijuana and
      cannabinoids.

PMID- 12237955
TI  - Effects of spindle removal on MPF and MAP kinase activities in porcine matured
      oocytes.
AB  - Intracellular localization of maturation/M-phase promoting factor (MPF) and
      mitogen activated protein (MAP) kinase in mature oocytes has been examined by
      immunocytochemical methods and the authors of these studies have reported that
      they are localized on spindles during M-phase. Although these reports showed the
      relative localization of MPF and MAPK on spindles, it has never been shown
      whether these kinases are present in the cytoplasm and, if they are present, how
      many parts of the kinases are localized on the metaphase spindle. In the present
      study, we made quantitative analyses of MPF and MAP kinase localized on oocyte
      spindles by kinase assays and immunoblotting after removal of the spindles from
      porcine mature oocytes. First, we certified their intracellular distribution by
      immunocytochemical methods and observed sharp signals of cyclin B1 on spindle
      poles and MAP kinase signals on the microtubule of metaphase spindles. In
      contrast to these results by immunostaining, the amounts of MPF and MAP kinase
      localized on spindles examined by immunoblotting and kinase assays were
      undetectable and less than 20%, respectively. These results indicate that the
      immunocytochemical technique is a powerful method for showing relative
      localization, but it is not suitable for quantitative analysis, and that the
      removal of metaphase spindles from mature oocytes does not have a severe negative
      impact on the subsequent MPF and MAP kinase activity and on the cell cycle
      progression in early embryo development.

PMID- 12237956
TI  - Nature's ingenuity: bypassing the classical secretory route via apocrine
      secretion.
AB  - Although it has been suggested that epithelial cells of the male reproductive
      system are involved in apocrine secretion, this method of secretion is not fully
      understood. In the present study, apocrine secretion was investigated in
      epithelial principal cells lining the epididymis and vas deferens (VD) of adult
      mice. The tissues were fixed by cardiac vascular perfusion with glutaraldehyde
      for routine electron microscope (EM) analysis and Bouin's fixative for light
      microscope (LM) immunocytochemistry to access functional roles. In the epididymis
      and VD, the apex of principal cells revealed protrusions of cytoplasm referred to
      as apical blebs (ABs). The latter contained solely numerous free ribosomes, 20 nm
      vesicles and few ER cisternae, suggesting segregation of their contents. While
      some ABs displayed wide areas of contact with the apical principal cell
      cytoplasm, others showed thin stalk-like attachment points as well as fissures at
      the junction of the two areas. Together with images of ABs and their contents
      deep in the lumen, it is suggested that ABs detach from principal cells whereupon
      they breakdown to release their contents therein. As ABs of the epididymis were
      immunoreactive for glutathione-S-transferases (GSTs) and ubiquitin, it is
      proposed that these proteins are synthesized on free ribosomes in ABs and that
      apocrine secretion represents the manner whereby they enter the lumen to
      effectively protect sperm from free radical injury and ubiquitinate proteins for
      degradation, respectively. ABs of the VD were immunoreactive for 3beta-HSD,
      suggesting that they are also capable of synthesis of steroids with their release
      via apocrine secretion. Taken together the data provide evidence for apocrine
      secretion in the adult mouse epididymis and VD that could play important roles in
      relation to sperm maturation, protection and viability.

PMID- 12237957
TI  - OR staffing holds up, but coping with shortage is more challenging.

PMID- 12237958
TI  - FDA wants to know more about reuse of opened-but-unused items.

PMID- 12237959
TI  - GPOs take steps toward codes of conduct.

PMID- 12237960
TI  - Leaders find ways to tackle staff shortage.

PMID- 12237961
TI  - A wish list for pack and tray packaging.

PMID- 12237962
TI  - JCAHO safety goals take effect in January.

PMID- 12237964
TI  - What does it take to staff a 5-room ASC?

PMID- 12237963
TI  - Arthroscopy no benefit for osteoarthritis.

PMID- 12237965
TI  - JCAHO: nurse shortage threat to patient safety.

PMID- 12237966
TI  - Relationship between concentration of citrate and ketone bodies in cow's milk.
AB  - The authors' hypothesis is that the members of the tricarboxylic acid cycle (TCA
      cycle) such as citrate decrease in association with increased ketone body
      formation. To prove this hypothesis the connection between ketone bodies and
      citrate formation of milk was studied. A fluorimetric method was used to
      determine citrate and a headspace sampling gas chromatographic (GC) method was
      developed for determination of ketone bodies. Under real conditions of milk
      sampling, transport and storage, preserved milk samples of 119 clinically healthy
      dairy cows obtained in the 48 hours after milking were investigated. A low level
      of acetoacetate (ACAC) was found in all samples. This fact can be explained by
      the spontaneous decarboxylation of acetoacetate during sample storage (previously
      decarboxylised acetoacetate = pdACAC) and, consequently, the majority of the
      amount of acetoacetate in the samples (AC + pdACAC) appeared in the measured
      acetone concentrations. Based on the measured acetone concentration of milk
      samples two groups were formed retrospectively: HA (high-acetone) group (n = 41)
      with an AC + pdACAC concentration of > 0.4 mmol/l and a LA (low-acetone) group (n
      = 78) with an AC + pdACAC level of < or = 0.4 mmol/l. In the milk of cows of
      Group HA a positive correlation (r = +0.623) and linear connection between
      acetone (AC + pdACAC) and beta-hydroxybutyrate (BOHB) levels was found [BOHB =
      2.491 + 0.586 x (pdAC + ACAC)]. Furthermore, in this group a negative correlation
      between citrate and BOHB and AC + pdACAC was also established (r = -0.579).
      Focusing on the results of this group the authors found a significant drop of AC
      + pdACAC and citrate during the metabolically critical first 1-4 weeks of
      lactation. For this reason they suggest that simple, easy, automated methods
      (i.e. flow injection analysis, Fourier transformation infrared analysis) should
      be introduced for the simultaneous determination of acetone and citrate
      concentration in milk to make the evaluation of the energy status of high
      producing dairy cows easier and more certain.

PMID- 12237967
TI  - Evaluation of flow injection analysis for determination of urea in sheep's and
      cow's milk.
AB  - Difficulties in measuring the urea content in sheep's milk often occur with
      spectral photometry due to the high protein and fat concentrations of the milk.
      In this study an enzymatic flow procedure (QuickChem 8000 Ion Analyser, Lachat
      Instruments, Milwaukee, USA) to determine the urea content in ovine and bovine
      milk was evaluated. Urea content is determined by the Berthelot reaction after
      splitting it enzymatically with urease. The free ammonia diffuses through a
      teflon membrane into a stream of reagent solutions. Detection takes place by
      means of a reaction between the ammonium ions with hypochlorite and salicylate
      producing a green colour, which is measured spectrometrically in a flow meter at
      660 nm. By using a diffusion cell chemical deproteinisation of milk is not
      necessary and capacity is high. The assessed procedure exhibited high accuracy
      and precision and reached a sample capacity of 55 samples an hour. Storage of the
      milk samples for several days as well as chemical preservation with bronopol had
      no effect on the measurement procedure. Due to the complexity of the apparatus
      and the costs associated therewith, the device proves less suitable for routine
      diagnostics but rather serves as a reference method for the measurement of urea
      concentration in milk.

PMID- 12237968
TI  - Two-dimensional and M-mode echocardiographic measurements of cardiac dimensions
      in healthy standardbred trotters.
AB  - The aim of the study was to establish normal echocardiographic values of healthy
      Standardbred trotters not published previously. Twenty-three clinically normal
      horses weighing between 350 and 490 kg were examined in the same manner: first a
      thorough physical and then detailed echocardiographic examination were performed.
      Standardised two-dimensional (2D) and guided M-mode echocardiographic imaging
      techniques were used to measure interventricular septal thickness (IVS), left
      ventricular internal diameter (LVID), left ventricular wall thickness (LVW), left
      atrial internal diameter (LAID) in end-systole (s) and end-diastole (d) and
      aortic diameter (AOD) in end-diastole. Mean, range and standard deviation of the
      different parameters were calculated. The mean values (in centimetres) were as
      follow (2D/M-mode): IVSs: 4.6/4.7; IVSd: 3.1/3.0; LVIDs: 7.0/7.0; LVIDd:
      10.7/10.7; LVWs: 3.9/3.9; LVWd: 2.7/2.7; LAIDs: 10.4/-; LAIDd: 11.3/-; AODd: 7.2/
      . Results of two-dimensional and M-mode measurements were compared to each other
      and to normal values obtained from other breeds.

PMID- 12237969
TI  - Occurrence of enteric redmouth disease in rainbow trout (Oncorhynchus mykiss) on
      farms in Croatia.
AB  - During the spring of 1996 and autumn of 1997 unusual mortality outbreaks among
      rainbow trout fry and yearlings occurred at two different trout farms, resulting
      in mortality of 20 and 10 per cent, respectively. Generally, the affected fish,
      swimming at the water surface, were reluctant to eat and were dark pigmented with
      visible haemorrhages around and within the oral cavity. Bacterial isolates from
      moribund fish from both cases were identified as Yersinia ruckeri by standard
      biochemical tests and API 20E. The isolated strains were found to be sensitive to
      tetracycline, chloramphenicol, co-trimoxazole, nalidixic acid, flumequine,
      enrofloxacin, carbenicillin and gentamicin. Microplate agglutination assay
      confirmed that both isolates belonged to serotype O1. The pathogenicity of the
      isolated bacteria was confirmed by challenge experiment. Titres of specific
      antibodies were determined in the sera of survivors. The titre was highest on the
      21st day postchallenge and was detectable until the 81st day.

PMID- 12237970
TI  - Torovirus detection in faecal specimens of calves and pigs in Hungary: short
      communication.
AB  - Bovine torovirus is an established aetiological agent of disease in cattle, while
      porcine torovirus has only been isolated from healthy animals. Evidence for the
      presence of torovirus has been described in several European countries and also
      in the United States. A survey was performed to detect toroviruses in Hungary by
      means of sampling ten swine and nine bovine herds. Rectal swabs and faecal
      specimens were collected from diarrhoeic calves and from weaned piglets. The
      samples were tested by the reverse transcription-polymerase chain reaction (RT
      PCR) using torovirus-specific primers and the positive samples were further
      examined by electron microscopy (EM). Torovirus was detected in 4 diarrhoeic
      calves (out of 111) and in 10 healthy weaned pigs (out of 200 tested),
      representing two of the 9 calf herds and two of the 10 pig herds tested. This is
      the first report of exact diagnosis of torovirus in Hungary.

PMID- 12237971
TI  - Clinical signs and mortality caused by Ornithobacterium rhinotracheale in turkey
      flocks.
AB  - Upper respiratory tract disease (manifesting itself in rhinitis, tracheitis and
      conjunctivitis) and mortality associated with Ornithobacterium rhinotracheale
      infection were observed in four flocks of 2- to 3-week-old turkeys. In a 15- to
      16-week-old turkey flock bilateral catarrhal-croupous pneumonia was found in the
      dead birds. In a further 5-week-old flock and in three 16- to 20-week-old turkey
      flocks mortality was preceded by nervous signs (motor disturbances, recumbency,
      abnormal carriage of the head) and was found to be associated with
      fibrinopurulent inflammation of the cranial bones and meningitis. The bacterium
      O. rhinotracheale was isolated from the affected organs in the different disease
      conditions. The isolated strains did not differ markedly in cultural,
      morphological and biochemical properties. This is the first report of a turkey
      disease manifesting itself in nervous signs associated with O. rhinotracheale
      infection.

PMID- 12237972
TI  - Effects of microbial phytase and 1,25-dihydroxycholecalciferol on the absorption
      of minerals from broiler chicken diets containing different levels of calcium.
AB  - The aim of this study was to investigate the effect of various calcium:total
      phosphorus (Ca:tP) ratios due to addition of microbial phytase and 1,25
      dihydroxycholecalciferol [1,25-(OH)2D3] on the absorption levels of minerals. In
      a 42-day experiment repeated three times, 144 day-old male broiler chicks (ISA
      220) were divided into six groups of eight chicks each. Diets containing two
      different (1:1 and 2:1) Ca levels were prepared. Groups 1, 2 and 3 received a
      diet of 1:1 Ca:tP ratio while Groups 4, 5 and 6 a diet of 1:2 Ca:tP ratio. These
      diets contained 1,25-(OH)2D3 and phytase in levels of 5 micrograms/kg and 600
      FYT/kg, respectively. The faeces was collected to analyse the absorption of
      minerals. At the end of the study, the absorption levels of Ca, P, Zn, Mn and Cu
      were increased by the addition of phytase enzyme (p < 0.05). This effect was
      obvious in the 3rd week. On the other hand, in the 6th week only Ca and P
      absorption levels were influenced positively by the addition of phytase enzyme.
      The results proved the positive effect of phytase, an enzyme which is used for
      increasing the utilisation rate of phytate P, Ca and other minerals in broilers.

PMID- 12237973
TI  - Mitosis and apoptosis in canine cutaneous histiocytoma and transmissible venereal
      tumour.
AB  - Cell proliferation and apoptosis in canine cutaneous histiocytomas and
      transmissible venereal tumours were examined in twenty cases. The Ki-67
      immunohistochemistry and Tunel methods were used to detect mitotic activity and
      apoptosis, respectively. The number of Ki-67 immunoreactive cells was 11.65 (+/-
      1.1706) in canine cutaneous histiocytomas and 17 (+/- 2.1751) in transmissible
      venereal tumours. The mean values of apoptotic cells for canine cutaneous
      histiocytomas and transmissible venereal tumours were 13.25 (+/- 1.8758) and 8.52
      (+/- 1.1007), respectively. It was considered that mitotic activity and apoptotic
      indices were useful in differentiation of canine cutaneous histiocytomas and
      transmissible venereal tumours. The correlation values for canine cutaneous
      histiocytomas and transmissible venereal tumours were 0.359 (+/- 0.330) and 
      0.232 (+/- 0.344), respectively. No significant (P > 0.05) correlation was found
      between mitosis and apoptosis in these two tumour types.

PMID- 12237974
TI  - Different action of IBMX, isoproterenol and rutin on orthovanadate-induced nitric
      oxide release in mouse macrophage cells.
AB  - The effects of cAMP-elevating compounds IBMX (3-isobutyl-1-methylxanthine) and
      isoproterenol, and that of rutin (an effective superoxide scavenger) were studied
      on orthovanadate--(a putative protein-phosphotyrosine phosphatase inhibitor)
      induced nitric oxide (NO) production in J774A.1 mouse macrophage cells. As we
      previously reported (Koncz and Horvath, 2000), rutin and sodium orthovanadate act
      synergistically to induce production of high amount of NO in J774A.1 cells. IBMX,
      an agent that can elevate cAMP level in the cells, can reduce the production of
      both the LPS- and rutin + orthovanadate-induced NO in macrophages. In contrast,
      isoproterenol, a non-selective beta-adrenergic receptor agonist, that reduced the
      LPS-induced NO production in macrophage cells, was unable to reduce the rutin +
      orthovanadate-induced NO production without negatively affecting cell viability.
      Moreover, isoproterenol dramatically enhanced the orthovanadate-induced NO
      synthesis in J774A.1 cells. Our previous study clarified that rutin and
      orthovanadate, in a specific concentration ratio of both, were able to produce
      hydrogen peroxide (H2O2). Using 2',7'-dichlorofluorescein-diacetate as a marker
      for H2O2, isoproterenol alone induced its oxidation but the rutin plus
      orthovanadate-induced H2O2 production was reduced by isoproterenol. These
      observations have revealed that, in some cases, H2O2 and superoxide (O2-)
      scavengers can act in a reverse mode on macrophage cells depending on the
      presence or absence of orthovanadate.

PMID- 12237975
TI  - Effect of deferoxamine and L-arginine treatment on lipid peroxidation in an
      intestinal ischaemia-reperfusion model in rats.
AB  - This study investigated lipid peroxidation (LPO) changes during intestinal
      ischaemia-reperfusion with and without deferoxamine or L-arginine treatment.
      White Wistar rats were allotted into four groups as follows: sham-operated (Group
      SOP), ischaemia-reperfusion only (Group I/R), I/R with deferoxamine (Group D) or
      L-arginine (Group A) treatment. Concentration of thiobarbituric acid reactive
      substances (TBARS), overall concentration of malondialdehyde and 4-hydroxy
      alkenals (LPO586), activities of superoxide dismutase (SOD) and glutathione
      peroxidase (GPX) of the jejunal homogenates were determined. The same analytes
      except LPO586 were assayed in RBC haemolysates. Measurements of ferric reducing
      ability (FRAP), total antioxidant status (TAS) and nitric oxide (NO)
      concentrations of plasma samples were also completed. The only significant change
      observed in the SOP group was an increased SOD activity after the ischaemic
      period. In the I/R group significant increase of intestinal LPO586 concentration
      was observed during hypoxia that was followed by similar changes in intestinal
      and RBC TBARS and plasma FRAP values upon reperfusion. In Group D the intestinal
      TBARS and LPO586 concentrations were significantly lower while FRAP and NO
      concentrations were significantly higher compared to the I/R group. At the same
      time RBC TBARS concentration and GPX activity significantly decreased within
      Group D. In Group A the intestinal LPO586 concentration was significantly lower
      than in the I/R group whilst RBC TBARS concentration showed a similar pattern.
      Plasma FRAP and NO concentration showed similar changes to those seen in Group D.
      It is concluded that I/R increased the LPO in the intestinal tissue and altered
      some parameters of plasma and RBCs, too. Deferoxamine treatment prevented these
      effects, while the usefulness of L-arginine remained doubtful.

PMID- 12237976
TI  - Training-induced alterations of the fatty acid profile of rabbit muscles.
AB  - The present study was designed to investigate whether meat-type rabbits are able
      to perform treadmill running as a daily routine exercise, and if so, whether the
      exercise induces specific proportional changes in the fatty acid composition of
      their muscles. After a four-week training period 8-week-old rabbits were
      slaughtered and the total activity of plasma lactate dehydrogenase was measured,
      showing a significant difference between the exercised and control groups (429 +/
      126 IU/l vs. 639 +/- 203 IU/l). Furthermore the fatty acid composition of m.
      longissimus dorsi (MLD) and m. vastus lateralis (MVL) was determined by means of
      gas chromatography. Exercise increased the proportions of oleic acid (C18:1 n-9)
      in both MLD and MVL as compared to the control group. However, the level of
      stearic (C18:0) and arachidonic (C20:4 n-6) acids significantly decreased in the
      MVL after the exercise. Changes in the fatty acid profile resulting from the
      physically loaded condition were of the same tendency in both muscles, adding
      that the MVL might have been exposed to the exercise more intensively;
      alterations there occurred in a more pronounced manner. Based on the inference
      that the composition of membrane structure was also affected, these alterations
      may have important consequences on meat quality.

PMID- 12237977
TI  - One-generation reproduction toxicity study of Dithane M-45 (mancozeb) and lead
      acetate.
AB  - The reproductive toxicity of lead acetate and of a fungicide formulation (Dithane
      M-45) containing 80% mancozeb was studied on rats. Lead acetate was applied in
      the feed in the following dose groups: control, 1,000, 5,000 and 10,000 mg/kg of
      diet. The three treatment groups received, in addition to the above doses of lead
      acetate, 4,500 mg/kg Dithane M-45 in the diet. The method was based on the OECD
      Guideline for Testing of Chemicals No. 415 (1981). Clinical symptoms and
      mortality were not found in the parent generation. The body weight of female
      animals decreased significantly before the pregnancy period. This tendency was
      also seen in males after the combination treatment. At the two high dose levels a
      remarkable body weight increase was seen in the female animals during the
      lactation period. As a result of treatment, decreased body weight of offspring
      was measured during the lactation period. No gross pathological changes were
      seen. Histological examination showed general tubulonephrosis in the experimental
      animals. It can be established that the administration of Dithane M-45 did not
      enhance the reproductive toxicity of lead acetate.

PMID- 12237978
TI  - If at first you don't succeed. False hopes of self-change.
AB  - Despite repeated failure at attempts to change aspects of their behavior, people
      make frequent attempts at self-change. The generally negative outcome of many
      such self-change efforts makes it difficult to understand why so many individuals
      persist at these attempts. The authors have described this cycle of failure and
      renewed effort as a "false hope syndrome" characterized by unrealistic
      expectations about the likely speed, amount, ease, and consequences of self
      change attempts. In this article, the authors further develop their
      conceptualization of this syndrome and review its evidential basis. They review
      the reasons why so many people tend to fail in their self-change attempts and
      then examine how people interpret these failures in such a way that they are led
      to keep trying repeatedly despite apparently overwhelming odds. Finally, the
      authors discuss the psychological consequences of repeated failure and analyze
      the distinction between confidence and overconfidence.

PMID- 12237979
TI  - Application of Megan's law to juveniles.
AB  - This article examines (a) the history of registration and notification statutes
      for sex offenders and the concerns and legal challenges they have faced, (b)
      psychology's limited knowledge about normal versus abnormal sexual development,
      and (c) research that suggests rates of recidivism for sexual offenses may be
      lower for juveniles than for adults who have been discovered and received
      punishment and/or treatment. Although the behaviors of juvenile and adult sex
      offenders may appear similar, the underlying mechanisms triggering the behaviors
      may be different or juveniles' patterns of behaviors may be less established,
      accounting for some of the observed differences in recidivism rates. Although the
      authors recognize the critical objective of protecting victims and potential
      victims, this article focuses on intervention efforts with juvenile sex
      offenders.

PMID- 12237980
TI  - Building a practically useful theory of goal setting and task motivation. A 35
      year odyssey.
AB  - The authors summarize 35 years of empirical research on goal-setting theory. They
      describe the core findings of the theory, the mechanisms by which goals operate,
      moderators of goal effects, the relation of goals and satisfaction, and the role
      of goals as mediators of incentives. The external validity and practical
      significance of goal-setting theory are explained, and new directions in goal
      setting research are discussed. The relationships of goal setting to other
      theories are described as are the theory's limitations.

PMID- 12237981
TI  - Network models contribute to cognitive and social neuroscience.

PMID- 12237982
TI  - Finding the findings in qualitative studies.
AB  - PURPOSE: To describe the challenges of finding the findings in qualitative
      studies. METHOD: Review of literature on representation in qualitative research
      and analysis of 99 reports of qualitative studies of women with HIV infection.
      FINDINGS: Factors complicating finding the findings in qualitative studies
      include varied reporting styles, misrepresentation of data and analytic
      procedures as findings, misuse of quotes and theory, and lack of clarity
      concerning pattern and theme. Theses and dissertations present special challenges
      because they often contain several of these problems. CONCLUSIONS: Given the
      varied beliefs about findings among qualitative researchers, the challenge is to
      find ways to present findings that will make them discernible to the diverse
      audiences for whom they are intended, including researchers and practitioners.

PMID- 12237983
TI  - Chronic stress, sense of belonging, and depression among survivors of traumatic
      brain injury.
AB  - PURPOSE: To test whether chronic stress, interpersonal relatedness, and cognitive
      burden could explain depression after traumatic brain injury (TBI). DESIGN: A
      nonprobability sample of 75 mild-to-moderately injured TBI survivors and their
      significant others, were recruited from five TBI day-rehabilitation programs. All
      participants were within 2 years of the date of injury and were living in the
      community. METHODS: During face-to-face interviews, demographic information, and
      estimates of brain injury severity were obtained and participants completed a
      cognitive battery of tests of directed attention and short-term memory, responses
      to the Perceived Stress Scale, Interpersonal Relatedness Inventory, Sense of
      Belonging Instrument, Neurobehavioral Functioning Inventory, and Center for
      Epidemiological Studies Depression Scale;. FINDINGS: Chronic stress was
      significantly and positively related to post-TBI depression. Depression and
      postinjury sense of belonging were negatively related. Social support and results
      from the cognitive battery did not explain depression. CONCLUSIONS: Postinjury
      chronic stress and sense of belonging were strong predictors of postinjury
      depression and are variables amenable to interventions by nurses in community
      health, neurological centers, or rehabilitation clinics. Future studies are
      needed to examine how these variables change over time during the recovery
      process.

PMID- 12237984
TI  - Postpartum depressed women's explanation of depression.
AB  - PURPOSE: To gain empirically derived knowledge of postpartum depression upon
      which to base detection and intervention strategies. DESIGN: From 1997 through
      2000, a sample of 30 nonhospitalized women, self-identified as postpartum
      depressed was recruited by network and "snowball sampling" to discuss their
      beliefs about postpartum depression. With reference to the Kleinman explanatory
      model of illness, their beliefs about postpartum depression and its treatment
      were contrasted to the biomedical model of postpartum depression. METHODS:
      Content analysis was done to classify data into cause, effect, severity,
      expectations, fears, and suggestions for treatment. Results were compared with
      DSM-IV diagnostic criteria. RESULTS: Postpartum depressed mothers' explanatory
      model of depression differed from the DSM-IV criteria for depression in that
      mothers' depiction was generally milder in form and consisted of sleep
      deprivation instead of sleep disorders. Also, mothers were confused, overwhelmed,
      and guilty about thoughts of hurting their babies. The mothers did not exhibit
      suicidal ideation. Mothers described the illness as severe and long lasting,
      causing multiple problems including marital discord. IMPLICATIONS: Mothers
      suggested more public education and support for new mothers to prevent and treat
      the disorder.

PMID- 12237985
TI  - An ecological perspective of breastfeeding in an indigenous community.
AB  - PURPOSE: To describe the sociocultural patterns that promote breastfeeding or
      weaning in the Ojibwe community, which has very low breastfeeding rates compared
      to the general population. DESIGN: A focused ethnographic approach with an
      ecological framework provided community level data. Semi-structured interviews (N
      = 52) were conducted in an urban Ojibwe community and with three groups of women:
      health or social service providers, women currently breastfeeding, or people who
      acted as resources. METHODS: Data were analyzed using an ethnographic approach.
      Group summaries were compiled and community-level patterns were identified.
      FINDINGS: Four patterns were identified that encompassed the influences of (a)
      Ojibwe and mainstream cultures (traditions), (b) communication-related barriers
      from a variety of sources (mixed messages), (c) socioeconomic issues (life
      circumstances) and (d) social support (nurturing and supporting). CONCLUSIONS:
      The values and practices of the studied group were not always congruent with
      those of the larger mainstream culture. Successful breastfeeding promotion and
      intervention programs based on culturally relevant perspectives are needed.

PMID- 12237986
TI  - Psychosocial and environmental influences on physical activity and health
      outcomes in sedentary women.
AB  - PURPOSE: To develop a model of psychosocial and environmental influences on
      physical activity and psychophysiological health outcomes in women. DESIGN: A
      structural equation model was evaluated. Variables included 13 predictors
      (perceived benefits to exercise, self-efficacy, goal setting, restructuring
      plans, relapse prevention, social support, work hassles, community hassles,
      family hassles, age, race, income, and education), two mediator variables
      assessing physical activity (performance, physical activity level), and three
      health outcome variables (body size, vigor, and fatigue). METHODS: A cross
      sectional sample of 198, self-described sedentary women aged 30-60 years
      completed several paper-and-pencil tests, after which they were assessed
      physiologically by means of performance on a 1-mile walk, BMI, and percentage of
      body fat measurements. RESULTS: Overall, the model showed good fit. Self
      efficacy, age, race, and income correlated with physical performance, and
      restructuring plans, relapse prevention, and age related to physical activity
      level. Performance was inversely correlated with body size, and physical activity
      level was directly related to perceived vigor. CONCLUSIONS: Findings indicate
      that psychosocial determinants are important factors in understanding physical
      activity and psychophysiological health, and thus they should be incorporated
      into intervention programs focused on increasing physical activity and improving
      health outcomes in women.

PMID- 12237987
TI  - Testicular self-examination in young adult men.
AB  - PURPOSE: To describe patterns of testicular self-examination (TSE) in a sample of
      young adult men and to identify factors distinguishing between men who do and do
      not practice TSE. DESIGN: A comparative descriptive design with a convenience
      sample of 191 adult men aged 18-35 years, recruited from a large industrial
      complex in the U.S. Midwest. Data were collected during several occupational
      health fairs held from 1999-2001. METHODS: A self-report, 75-item health risk
      appraisal (HRA) was administered to identify health-related lifestyle habits. Men
      who did and did not perform TSE regularly were compared using Mann-Whitney U
      statistics for discrete variables and t tests for continuous data. Discriminant
      function analysis was used to identify factors allowing prediction of frequent or
      infrequent TSE performance. FINDINGS: Sixty-four percent of 191 participants
      reported rarely or never performing TSE, and 36% practiced TSE monthly or every
      few months. Men who infrequently performed TSE were more often African American
      or Hispanic and had less than a college education. Other significant factors
      associated with infrequent TSE practice included less satisfaction with current
      job assignment; less satisfaction with life in general; greater worries
      interfering with daily life; more serious family problems in dealing with spouse,
      children, or parents; and reduced availability of people to turn to for support.
      CONCLUSIONS: Demographic and socioeconomic variables were related to TSE
      knowledge and performance. Further investigation is required to determine why
      men, especially ethnic minority men, are not performing this important cancer
      screening activity.

PMID- 12237988
TI  - Outcomes of therapeutic massage for hospitalized cancer patients.
AB  - PURPOSE: To examine the effects of therapeutic massage on perception of pain,
      subjective sleep quality, symptom distress, and anxiety in patients hospitalized
      for treatment of cancer. ORGANIZING CONSTRUCT: Rogers' Science of Unitary Human
      Beings and Watson's theory of human caring. METHODS: Quasiexperimental. The
      sample consisted of 41 patients admitted to the oncology unit at a large urban
      medical center in the United States for chemotherapy or radiation therapy. Twenty
      participants received therapeutic massage and 21 received the control therapy,
      nurse interaction. The outcome variables were measured on admission and at the
      end of 1 week via the following instruments: a Numerical Rating Scale for pain
      intensity and Likert-type scale for distress from pain; The Verran Snyder-Halpern
      Sleep Scale, McCorkle and Young's Symptom Distress Scale, and the Speilberger
      State Anxiety Inventory. ANOVA and t tests were used to analyze between and
      within group differences in mean scores and main effects on outcome variables.
      FINDINGS AND CONCLUSIONS: Mean scores for pain, sleep quality, symptom distress,
      and anxiety improved from baseline for the subjects who received therapeutic
      massage; only anxiety improved from baseline for participants in the comparison
      group. Statistically significant interactions were found for pain, symptom
      distress, and sleep. Sleep improved only slightly for the participants receiving
      massage, but it deteriorated significantly for those in the control group. The
      findings support the potential for massage as a nursing therapeutic for cancer
      patients receiving chemotherapy or radiation therapy.

PMID- 12237989
TI  - Implicit memory and familiarity among elders with dementia.
AB  - PURPOSE: To propose a framework for familiar environment as a cue for maintaining
      or maximizing functional abilities in elders with dementia. ORGANIZING CONSTRUCT:
      The organizing construct is the sense of familiarity. Although a feeling of
      familiarity can be processed in both explicit and implicit memory in normal
      populations, it is retrieved more frequently and efficiently in the implicit
      memory system than through explicit memory in elders with dementia. METHODS: The
      model was developed using sources identified through a literature search of
      relevant topics in Medline, PsycInfo, and CINAHL, as well as through clinical
      observations and experiences. CONCLUSIONS: Evidence from neuro- and cognitive
      psychology indicates that elders with dementia or Alzheimer's disease (AD) have
      impaired explicit memory but preserved implicit memory. For initiating an
      intervention related to spared implicit memory, we propose that implicit memory
      can be used therapeutically in patients with dementia. The sense of familiarity
      as a form of implicit memory is used as an exemplar. Producing or introducing the
      sense of familiarity into a new or strange environment as well as maximizing
      familiarity in an existing environment is proposed as a viable nursing strategy.

PMID- 12237990
TI  - A new foundation for methodological triangulation.
AB  - PURPOSE: To show how triangulation with qualitative and quantitative methods can
      help confirm a theory to a greater degree than can either method alone.
      CONSTRUCT: Coherence view of theory structure and confirmation. Evidence helps
      confirm a theory if the theory is the most coherent way of accounting for the
      evidence, and one theory is more coherent than another insofar as it leaves fewer
      unanswered questions (and fewer unquestioned answers). METHODS: The method of
      this theoretical essay is analytic. Analysis of the debate over methodological
      triangulation reveals presuppositions about theory structure and confirmation.
      Well-known arguments in the philosophy of science are presented to show that the
      presuppositions are false. The arguments provide evidence for the construction of
      an alternative, coherence model of theory structure and confirmation. FINDINGS:
      Three consequences of the analysis are: (a) qualitative and quantitative methods
      do not produce theories with different structures; (b) qualitative and
      quantitative methods help to confirm theory in the same ways; and (c) used
      together, qualitative and quantitative methods can confirm a theory to a greater
      degree than the use of either method alone. CONCLUSIONS AND IMPLICATIONS: A
      coherence of model of theory structure and confirmation supports a version of the
      blending view of methodological triangulation. Triangulation can provide
      completeness, abductive inspiration, and confirmation. This version of blending
      provides principles for resolving issues of methodological dominance and order,
      and it indicates how different methods can disconfirm theory.

PMID- 12237991
TI  - Economic evidence for evidence-based practice.
AB  - PURPOSE: To explicate (a) the types of economic analyses available to nurses, (b)
      the measurement of costs in different types of economic evaluations, (c)
      recommendations for standardization, and (d) the assessment of economic
      evaluations for evidence-based practice. METHODS: Five types of economic analyses
      are reviewed. Recommendations for standardization of cost-effectiveness analyses
      are included as well as a worksheet for use in critiquing economic evaluations
      for validity and applicability to clinical settings. FINDINGS: Limited knowledge
      and a lack of consistent approaches to economic analyses are evident in the
      nursing and health care literature. However, nurses have not contributed to the
      conduct of rigorous economic evaluations or research to the extent found in other
      health care disciplines. CONCLUSIONS: Basing nursing practice on the best
      available evidence is now the expected standard of care. Applying economic
      evidence to practice requires understanding the methods used to conduct economic
      evaluations and to analyze the rigor of such evaluations.

PMID- 12237992
TI  - What the emerging workforce wants in its leaders.
AB  - PURPOSE: To describe desired traits as perceived by emerging and entrenched
      workforce members. DESIGN AND METHODS: A national sample of nursing students (n =
      108) and a sample of Midwestern American hospital managers (n = 126) were
      categorized by age and asked to rank the traits desired in their leaders.
      Participants ranked the most desired and least desired traits of leaders.
      Rankings were compared between groups as well as with desired traits from
      leadership studies in the 1990s. FINDINGS: A high degree of congruency was found
      between emerging and entrenched health care workforce respondents. However, these
      findings showed little congruence with previous studies. CONCLUSIONS: Congruence
      of expectations facilitates mentoring relationships, so finding no difference
      between the older and younger groups bodes well for the mentoring of young nurse
      leaders. The key implication is the challenge to recruit and retain such leaders
      in the nursing profession in a systematic, logical, and generation-friendly way.

PMID- 12237993
TI  - Children's perceptions of TV and health behavior effects.
AB  - PURPOSE: To understand and document children's stated experiences and beliefs
      about television and to elicit their suggestions for alternative activities.
      DESIGN AND METHODS: Eleven focus groups were conducted with 51 Anglo and Latino
      children, ages 7-10, in a large Northern California city. Philosophical
      underpinnings of developmental psychology were the basis for multiphase thematic
      analysis. Data were collected in 1998-1999. RESULTS: Themes were identified in
      five conceptual categories. Findings showed that children did not perceive many
      parental rules related to TV watching, rather daily routines are associated with
      TV viewing. Children revealed both covert and overt motivations for watching.
      Nearly all participants spoke of the deception of advertising, but they were
      unclear about the role of commercial sponsors in payment for TV shows. Children
      perceived both negative physical and behavioral health effects of TV and they had
      great difficulty imagining life without a TV. CONCLUSIONS: Children perceived
      television as providing educational and relational needs. Although they preferred
      alternatives to TV, they had difficulty articulating and getting those needs met.
      Clinicians and researchers can utilize these findings to design health
      interventions that attenuate the health-impairing effects of habitual sedentary
      activity in childhood.

PMID- 12237994
TI  - [Dialysis and vascular access ports].

PMID- 12237995
TI  - [Cystatin C--a new marker to diagnose renal insufficiency of mild degree].

PMID- 12237996
TI  - [Forced-use therapy of hand--a promising rehabilitation method in stroke
      patients].

PMID- 12237997
TI  - [Enlarged pelvic lymph nodes after immunotherapy in a patient with bladder
      cancer].

PMID- 12237998
TI  - [Pyoderma gangrenosum--a less well known ulcerous skin disease].

PMID- 12237999
TI  - [New imaging strategies to diagnose lung diseases].

PMID- 12238000
TI  - [Radiological terminology of the lungs].

PMID- 12238001
TI  - [The thersites complex--a plastic surgeon's nightmare].

PMID- 12238002
TI  - [Pain in head and neck and ocular ptosis].

PMID- 12238003
TI  - [Adult obesity].

PMID- 12238004
TI  - [Problem with restenosis in connection to balloon angioplasty near to be solved].

PMID- 12238005
TI  - [Will drug marketing help to turn patients to well-educated consumers?].

PMID- 12238006
TI  - [Polycystic ovarian syndrome is a health risk].

PMID- 12238007
TI  - [Duodecim Terveysportti offers improved member services].

PMID- 12238008
TI  - [Anemia in children].

PMID- 12238009
TI  - Senate and Assembly hold joint health committee hearing on nursing shortage and
      nurse staffing crisis.

PMID- 12238010
TI  - Self report of research skills and knowledge of health professionals.
AB  - Considerable attention has been paid to Outcomes Based Practice in the
      literature. In order to enhance the use of outcomes based research at the
      bedside, the Interdisciplinary Research Committee at Robert Wood Johnson
      University Hospital in New Brunswick, NJ implemented the "Self Report of Research
      Skills and Knowledge of Health Professionals" research project. This replication
      study will be used to obtain baseline data that will enable the Interdisciplinary
      Research Committee to tailor educational offerings that will increase the use of
      research in the daily activities of clinical staff members.

PMID- 12238011
TI  - The nursing research corner.
AB  - Precede the abstract with the title of the manuscript. Prepare a structured
      abstract with the following sections (include these headings): BACKGROUND:
      Summarize the literature review, demonstrating the need for this study.
      OBJECTIVES: Clearly state the main question or hypothesis of this study in one
      sentence. METHODS: Describe the study design, participants, and measurements used
      in a few sentences. RESULTS: Describe the main results in a concise paragraph.
      This section should be the most descriptive. Note levels of statistical
      significance and confidence intervals were appropriate. CONCLUSION(S): Make
      conclusions based only on the reported results. Describe any further study
      needed. Manuscripts are reviewed anonymously by members of an expert panel. The
      decision with regard to publication is based on the reviews. Authors should not
      identify themselves in the manuscript other than on the title page, which is
      removed before review. The Nursing Research Corner is a peer-reviewed column.
      Manuscripts are submitted to two members of an expert panel for blind review. The
      first author will be notified following the review process.

PMID- 12238012
TI  - Study reveals link between increased nursing care, better patient outcomes in
      hospitals.

PMID- 12238013
TI  - Seniors connect: a partnership for training between health care and public
      libraries.
AB  - Kaleida Health Libraries, in partnership with the Buffalo and Erie County Public
      Library, presented "Seniors Connect: A Health Information Project." The program
      was funded by the Community Foundation for Greater Buffalo and the Kaleida Health
      Foundation. The purpose of the project was to teach African-American and Hispanic
      senior citizens or their caregivers residing in the city of Buffalo how to search
      the Internet to find quality, accurate, understandable health information.
      Attendees were taught to distinguish quality information from inaccurate,
      misleading, and fraudulent material. A total of fourteen training sessions were
      offered. The Seniors Connect program was initiated with health fair at each
      branch library, conducted by Kaleida Health staff, to provide an opportunity for
      participants to learn about health care services available in their community;
      observe demonstrations of health information searches on the Internet; learn
      about new treatment modalities for diseases such as diabetes, high cholesterol,
      thyroid abnormalities, and hypertension; and interact with area health care
      providers and library staff. The sessions were highly rated by attendees and many
      participants expressed their gratitude for a program geared specifically toward
      seniors.

PMID- 12238015
TI  - Consumer Health Informatics--integrating patients, providers, and professionals
      online.
AB  - Consumer Health Informatics (CHI) means different things to patients, health
      professionals, and health care systems. A broader perspective on this new and
      rapidly developing field will enable us to understand and better apply its
      advances. This article provides an overview of CHI discussing its evolution and
      driving forces, along with advanced applications such as Personal Health Records,
      Internet transmission of personal health data, clinical e-mail, online
      pharmacies, and shared decision-making tools. Consumer Health Informatics will
      become integrated with medical care, electronic medical records, and patient
      education to impact the whole process and business of health care.

PMID- 12238014
TI  - Video as a format in health information.
AB  - Video is a medium that has passed through a progression of technical advances
      including the invention of videotape, the incremental refinements to laser
      videodisc technologies, and the arrival of digital imaging technologies such as
      CD-ROM, DVD, and the Web's video streaming. Today, video is firmly established as
      a convenient and effective medium for conveying medical information. One result
      of these developments is that medical reference librarians can expect to
      encounter information requests and professional tasks that will require an
      understanding of these wide-ranging and differing video technologies.

PMID- 12238016
TI  - From EBM to EBL: two steps forward or one step back?
AB  - The author employs his vantage point as a contributor to Evidence-based Medicine
      (EBM) and Evidence-based Librarianship (EBL) in the United Kingdom to anticipate
      obstacles to be overcome by the emerging EBL paradigm. After reviewing and
      synthesizing three proto-definitions of EBL, he discusses issues around the
      potential domains to be populated by research findings. He then briefly considers
      the contribution that critical appraisal skills can make to an evidence-based
      profession. In concluding that "evidence-based librarianship" is a self-limiting
      "label," he encourages health information professionals instead to promote the
      contribution of librarianship to evidence-based practice, a role for which they
      are uniquely qualified.

PMID- 12238017
TI  - Two new psychology databases: e-psyche and psycARTICLES.

PMID- 12238018
TI  - Developmental disability resources on the Internet.

PMID- 12238019
TI  - The value of hospital library benchmarking: an overview and annotated references.

PMID- 12238020
TI  - Medical informatics: the Pittsburgh experience.
AB  - This column reports the results of a survey conducted of medical librarian
      participants in medical informatics training at the University of Pittsburgh.
      This small study was undertaken in order to identify issues in training different
      kinds of library and information science practitioners in medical informatics.

PMID- 12238021
TI  - [Microdeletion syndromes].
AB  - New high-resolution cytogenetical technique identified an increased number of
      terminal, interstitial and subtelomeric microdeletion as the etiology of many
      syndromes of multiple congenital anomalies, mental retardation and facial
      dysmorphy. A loss of contiguous genes shows a high phenotypical variability and
      at the same time it is significant for genetic prognosis. 1) Variability of
      clinical features depends on the size and pathogenetic mechanism of underlying
      deletion; 2) Dysmorphic face features are of a characteristic type and can be
      somatoscopically recognized; 3) Heart defects and mental retardation are common
      features of microdeletion syndromes; 4) New mutations represent the most common
      etiology of microdeletions; only 1 to 10% of mutations are transmitted from the
      parental gonadal mosaics, from the balanced translocation or from the same
      microdeletion in parents; 5) Recurrence risk is low, but it may be as high as 50%
      in individual cases of inherited mutation; 6) Genetic heterogeneity is high and
      the responsible genes can be located at different chromosomes (e.g. Di George
      syndrome due to mutation on 22q or 10q) and can also result from microdeletion or
      point mutation (in the Shprintzen syndrome 70% represent microdeletion and 30%
      point mutation at 22q11, in Rubinstein-Taybi syndrome 10% cases result from
      microdeletions and 90% from point mutations); 7) Population incidence of
      microdeletions is high (1:4000 to 1:30,000) because their etiologic mechanism is
      related to the common unequal crossing over; 8) Imprinting plays a role in some
      cases, e.g. Prader-Willi syndrome results from nullisomy of paternal 15q12
      chromosome, Angelman syndrome is related to that of maternal 15q12 chromosome; 9)
      Prenatal prevention of the high risk familial chromosomal rearrangements is
      feasible since the 12th gestation week.

PMID- 12238022
TI  - [Methods of expressing the strength of expert proof of paternity determination].
AB  - Non-exclusion from paternity of alleged man can be quantified by pre-test and
      post-test parameters. Author advocates the view that expression of the power of
      forensic expert evidence by likelihood ratio, which compares probability of data
      under two hypotheses, is the best approach from both the point of forensic
      mathematics and judiciary practice. Advantage of likelihood ratio is described
      and demonstrated on microsatellite typing examples.

PMID- 12238023
TI  - [Genetics of autism].
AB  - Autism is a severe psychiatric disorder characterised by deficits in social
      interaction, disturbed communication and adherence to stereotype routines and
      interests. Nowadays it is completely clear that this disorder has a biological
      basis and many observations show strong genetic determination of autism. The
      importance of genetic factors is supported by frequent association of this
      disorder with known hereditary diseases or with various chromosomal aberrations,
      by high concordance of the disorder in monozygotic twins, higher risk for the
      siblings of autistic patients and also by the frequent occurrence of milder
      symptoms of the autistic spectrum in more distant relatives. All these findings
      show that the autistic phenotype results from unfavourable combination of alleles
      of several genes in interplay with factors of the environment. This model of
      multifactorial inheritance of autism serves at present as the starting point for
      the search for predisposing genes in the human genome. The association is tested
      between autism and alleles of candidate genes selected based on known biochemical
      and physiological role of their protein products, or based on their location
      close to recurrent chromosomal rearrangements or in regions identified by whole
      genome linkage analyses. Studies of most of these genes have not yielded clear
      cut results yet, but the participation of some of them in the aetiology of autism
      is possible.

PMID- 12238024
TI  - [Genetic study of 20 patients with autism disorders].
AB  - BACKGROUND: Many observations indicate that genetic factors play an important
      role in the aetiology of autism. Up to now, however, no genetic markers have been
      convincingly identified which influence the predisposition to this disorder.
      Complex genetic analysis of autistic patients and their families may therefore
      lead to the identification of features which could help to direct further search
      for the predisposing genes. METHODS AND RESULTS: We have analysed a sample of 20
      patients with autism spectrum disorders. The patients have been subjected to
      clinical genetic examination, cytogenetic analysis and DNA analysis of the FMR1
      gene. In the sample studied we have observed more boys (15/20), various degree of
      mental retardation (18/20), high frequency of complications during pregnancy
      (10/20) and delivery (10/20), increased incidence of psychiatric disorders,
      behavioural abnormalities and suicides among the relatives, and increased head
      circumference and unusually formed ears in the probands. Three patients had
      different chromosomal aberrations or variants (t(21;22), inv(9) and inv(10)). One
      patient harboured expansion of the trinucleotide repeat sequence in the FMR1 gene
      on the full mutation level which is characteristic for the fragile X syndrome,
      and one patient is suspected to suffer from the Rett syndrome. CONCLUSIONS: Our
      observations confirm and extend the results reported in the literature. Most
      interesting are mainly the macrocephaly which may be associated with the recently
      described increased neonatal levels of neural growth factors in autistic
      individuals, ear malformations which may indicate aberrations in the HOXA1 gene
      pathway, the occurrence of chromosomal inversions recurrent in autism, and
      peculiarities in the pedigrees of the patients.

PMID- 12238025
TI  - [Percutaneous treatment of malignant stenoses of the biliary tract].
AB  - Experience with treatment of more than 800 patients with malignant stenosis of
      the biliary tract is reviewed. The significance of complex treatment using simple
      internal or external drainage, stent introduction, brachytherapy, percutaneous
      actinotherapy and locoregional chemotherapy is presented. Advantages of
      individual percutaneous methods are compared and indications for using metallic
      stent in patients with malignant stenosis of the biliary tract are evaluated.
      Significance and indications for the percutaneous treatment is discussed and its
      advantages are compared with the endoscopic approach.

PMID- 12238026
TI  - [Long-term follow-up of the health status of opiate abusers treated with
      methadone--pilot study].
AB  - BACKGROUND: Examination of the health status of patients abusing opiates can be
      substantiated by their high morbidity. The aim of the work was to describe the
      actual health status and the extent and seriousness of the affliction before the
      substitution therapy with opioid receptors agonist--methadone. METHODS AND
      RESULTS: The group of drug abusers consisted of 101 persons (average age was 28.5
      years, within the range of 20 to 47 years, 77 men and 24 women). Among the
      pathological findings, values of the levels of hepatic enzymes ALT, AST (35 and
      31%), GMT (9%), low haemoglobin levels (24%) and elevated values of IgM (38%) and
      CRP (25%) belonged to the most frequent ones. Because of the simultaneously
      positive tests for hepatitis (C and B, 70% and 61%), the alteration is fully
      obvious. Low testosterone levels in males (63%) indicate the dysfunction of the
      hypothalamus-hypophysis-gonadas axis. Increased values of thyroxin (14%), P (20%)
      and atherogenity index (19%) remain unexplained. Several other laboratory
      biochemical parameters remained within the physiological range. Imaging methods
      revealed hepatomegaly in 28% and splenomegaly in 27%, echotexture indicating
      steatosis was found in 15% of studied persons. CONCLUSIONS: In chronic drug
      abusers before the onset of the substitution therapy, it is possible to expect
      frequent alterations, namely that of hepatic functions, positive test for
      hepatitis B and C, alteration of immunoglobulines level and testosterone deficits
      (in males).

PMID- 12238027
TI  - [Perioperative tachyarrhythmia].
AB  - Sudden onset of tachyarrhythmias in an operating theatre or an intensive care
      unit can be a frustrating experience for an attending physician and sometimes
      even for his patient, not only because of severity of patient's clinical state,
      but also for the mental stress loaded on him by collaborating surgeons. From that
      reason, a diagnosis and treatment of such condition should be intensive, simple,
      effective and safe for the patient. Increased activity of sympathoadrenal system
      is the main pathophysiological condition in the pathogenesis of perioperative
      arrhythmias that can provoke sinus tachycardia followed with a transient
      myocardial ischaemia and other deleterious effects. Sympathetic nervous system
      stability plays an important role in the prevention and treatment of
      perioperative arrhythmias. In this review article, the author highlights a basic
      electrophysiology and molecular pathophysiology of heart rhythm disturbances, and
      on the background of recent clinical studies he tries to propose a simplified
      therapeutic algorithm for treatment of these difficult states. Beta-blockers and
      group III, antiarrhythmics of Vaughan-Williams classification (amidarone) are
      recommended as the optimal remedies for the treatment of tachyarrhythmias in the
      perioperative period.

PMID- 12238028
TI  - [Manipulation of hematopoietic stem cell grafts and their use in clinical
      practice].
AB  - Autologous stem cell transplantation has been successfully used in treatment of
      various hematological malignancies and solid tumors in children and adults.
      Published data have confirmed that bone marrow harvests and peripheral blood stem
      cell collections frequently contain a significant number of tumor cells.
      Contaminating tumor cells can contribute to the disease relapse in posttransplant
      period, so attempts are made to eliminate contaminating tumor cells from
      autografts. In the case of allogenic transplantation, T-lymphocytes depletion
      from graft decreases the risk of the graft versus host disease after
      transplantation. In this article we comment techniques available and method used
      for elimination of tumor cells. Commentary is aimed on potential benefits and
      risks of every method.

PMID- 12238029
TI  - [Nutritional determinants of homocysteinemia].
AB  - BACKGROUND: Vitamin B12, folate and vitamin B6 are the main determinants of
      homocysteinemia. These B-group vitamins influence two metabolic pathways of
      homocysteine reduction, which prevail in dependence to methionine intake.
      Transsulfuration (vitamin B6) dominates under condition of overnutrition with
      prevalence of animal food sources, remethylation (vitamin B12 and folic acid) is
      decisive under conditions of malnutrition, alternative nutrition or optimal
      traditional diet. METHODS AND RESULTS: Plasma homocysteine and folic acid,
      vitamins B12 and B6 in serum were measured in alternative nutrition groups of
      adults (vegans, vegetarians (lacto + lactoovo), semivegetarians, n = 39) and
      compared with those values in group consuming traditional diet--control group,
      general population (n = 35). In alternative nutrition groups, the average
      homocysteine level is significantly higher (vegans 17.2 mumol/l, vegetarians 12.9
      mumol/l, semivegetarians 10.1 mumol/l, control group 9.9 mumol/l); the frequency
      of hyperhomocysteinemia (over 15 mumol/l) is 50%, 32%, 14% vs. 6% in control
      group. Vegetarians and vegans have a significantly higher levels of vitamin B6
      and folic acid; the frequency of vitamin B6 deficit is 60% and 57% in control
      group and semivegetarian group vs. 16% and 0% in vegetarian and vegan group.
      Folate deficit was found in 16% of traditional group vs. 0% in alternative
      groups. Serum levels of vitamin B12 are significantly reduced in subjects
      consuming alternative nutrition with deficiency observed in 67% of vegans, 32% of
      vegetarians, 14% of semivegetarians vs. 0% in control group. CONCLUSIONS: Vitamin
      levels in relation to nutritional regime and metabolic pathways of homocysteine
      show that the mild hyperhomocysteinemia in alternative nutrition is a consequence
      of vitamin B12 deficiency. In traditionally fed population, higher plasma
      homocysteine values is caused by folate deficiency. These conclusions are
      supported by a significantly negative linear correlation of homocysteine--folic
      acid levels (traditional nutrition) and homocysteine--vitamin B12 levels
      (alternative nutrition). In case of vitamin B6, a similar correlation was not
      found.

PMID- 12238030
TI  - [Analysis of specific sequences in female patients with Turner syndrome--initial
      study].
AB  - BACKGROUND: DNA sequences from chromosome Y can cause gonadoblastoma development
      in patients with Turner syndrome (TS). Estimated risk is about 30%. The aim of
      the study is detection of Y-sequences of DNA level, calculation of mosaicism and
      its cytogenetic location. Clinical result of the study is the recommendation to
      gonadectomy of proved positive patients. METHODS AND RESULTS: Samples from 110
      patients were collected. The PCR method and analysis of products on agarose gel
      was compared with analysis of DNA fragments from quantitative fluorescent (QF)
      PCR on capillary electrophoresis. The loci DYZ3, AMGX/Y and SRY were used for
      detection. The method QF PCR was effected for DYZ3 and AMGX/Y loci. The positive
      cases were examined by FISH method. Five (4.5%) and 3 (2.7%) positive cases were
      detected in DYZ3 and SRY resp. loci by electrophoresis on agarose gel. Seventeen
      (15.5%) and 7 (6.4%) positive cases were detected in DYZ3 and AMGX/Y resp. by
      capillary electrophoresis. The estimated mosaicism ranged from 1:5 to 1:100,000.
      CONCLUSIONS: QG PCR is the most sensitive method for diagnostics of Y-sequences.
      Simultaneously the incidence of Y-positive cells can be estimated. The positive
      cases with marker in karyotype were confirmed by FISH.

PMID- 12238031
TI  - [Accurate noninvasive diagnosis of Helicobacter pylori infection using antigen
      determination in the feces in the pediatric population].
AB  - BACKGROUND: H. pylori can cause several gastroduodenal diseases. Because H.
      pylori infection is usually acquired in childhood, accurate diagnosis of the
      infection in the pediatric population is important. Tests for the diagnosis of H.
      pylori infection can be divided into invasive and noninvasive. The aim of our
      study was to compare invasive tests (endoscopy, gastric mucosal biopsy,
      histology) and the noninvasive, newly developed stool antigen test to diagnose H.
      pylori infection. METHODS AND RESULTS: 91 children (40 boys, 51 girls, mean age
      12.6 +/- 3.5 years) with dyspeptic symptoms were tested for H. pylori infection
      using endoscopy and gastric biopsy and a new antigen test in stool samples
      (immunoassay). Thirty-one of the children (34.1%) with dyspepsia were found
      positive for H. pylori according to histologic examination and rapid urease test.
      In 28 of the 31 patients, H. pylori stool antigen could be detected (sensitivity
      90.3%). Of the 60 patients with negative direct histologic examination and rapid
      urease test, 60 were H. pylori--negative in stool antigen test (specificity
      100%). Positive predictive value of stool antigen test is 100% and negative
      predictive value is 95.2%. CONCLUSIONS: The stool antigen test is highly
      sensitive and specific. It will be potentially very helpful in the diagnosis of
      H. pylori infection and can replace endoscopy for detection of H. pylori
      infection in children with comparable accuracy and reliability.

PMID- 12238032
TI  - [Principles, methods and use of the National Register of Cardiovascular
      Interventions].
AB  - The goal of cooperative project of the national registry of cardiovascular
      interventions is analysis of quality of cardiovascular care with risk
      stratification and assessment of clinical indicators at organizational and
      individual level. Bayes methodology of stratification and risk prediction is
      used.

PMID- 12238033
TI  - [Treatment of diabetics at the Institute of Clinical and Experimental Medicine
      (IKEM)].

PMID- 12238034
TI  - [Development and prospects of clinical diabetology].

PMID- 12238035
TI  - [Expectations of diabetology in future].

PMID- 12238036
TI  - [Molecular mechanisms in digestion and absorption of carbohydrate].

PMID- 12238037
TI  - [Gluconeogenesis and glycolysis].

PMID- 12238038
TI  - [TCA cycle, oxidative phosphorylation and uncoupling protein].

PMID- 12238039
TI  - [Glucose transporter].

PMID- 12238040
TI  - [Molecular mechanisms of glucose transport in renal proximal tubules].

PMID- 12238041
TI  - [Review: regulation of glucose metabolism].

PMID- 12238043
TI  - [Biosynthesis of insulin molecule and its chemical structure].

PMID- 12238042
TI  - [The regulation of insulin gene transcription by transcription factors].

PMID- 12238044
TI  - [Mechanism of glucose-induced insulin secretion].

PMID- 12238045
TI  - [Ion channel mechanisms in insulin secretion].

PMID- 12238046
TI  - [Historical development of concept of diabetes mellitus].

PMID- 12238047
TI  - [Role of NADH shuttle system in glucose-stimulated insulin secretion].

PMID- 12238049
TI  - [Molecular mechanism of insulin exocytosis and the role of SNARE proteins].

PMID- 12238048
TI  - [Neurohormonal regulation of insulin secretion].

PMID- 12238050
TI  - [Secretion and metabolism of insulin].

PMID- 12238051
TI  - [Insulin receptor gene, biosynthesis and structure].

PMID- 12238052
TI  - [Insulin action: its variety and diversity].

PMID- 12238053
TI  - [The mechanism of insulin receptor activation upon insulin binding].

PMID- 12238055
TI  - [Glucagon and GLP (glucagon-like peptide)].

PMID- 12238054
TI  - [Signal transduction from the insulin receptor].

PMID- 12238056
TI  - [Somatostatin].

PMID- 12238057
TI  - [Gastrointestinal hormones in diabetes mellitus].

PMID- 12238058
TI  - [Mechanism of GH induced insulin resistance].

PMID- 12238059
TI  - [Biogenic amines (catecholamines, catecholamine receptors and others)].

PMID- 12238060
TI  - [History and perspective of classification for diabetes mellitus].

PMID- 12238061
TI  - [Glucocorticoid].

PMID- 12238062
TI  - [The effect of estrogen on adiposity and metabolism].

PMID- 12238063
TI  - [The other gastrointestinal hormones in diabetes mellitus].

PMID- 12238064
TI  - [Hepatic glucose metabolism and its regulation].

PMID- 12238065
TI  - [Glucose metabolism and its regulation in skeletal muscle].

PMID- 12238066
TI  - [Glucose metabolism in the brain].

PMID- 12238067
TI  - [Glucose metabolism in vascular endothelial cells].

PMID- 12238068
TI  - [Carbohydrate metabolism in the small intestine].

PMID- 12238069
TI  - [Glucose metabolism in the kidney].

PMID- 12238070
TI  - [Glucose metabolism in red blood cells].

PMID- 12238071
TI  - [Pancreatic development and differentiation factors of beta cell].

PMID- 12238072
TI  - [Structure and function of islets of Langerhans].

PMID- 12238073
TI  - [Diagnosis of diabetes mellitus from past to future].

PMID- 12238074
TI  - [Classification of diabetes mellitus].

PMID- 12238075
TI  - [General aspects on etiology, classification and pathogenesis of type 1
      diabetes].

PMID- 12238076
TI  - [Susceptibility genes for type 1 diabetes].

PMID- 12238077
TI  - [Molecular mechanisms of pancreatic beta-cell destruction in type 1 diabetes].

PMID- 12238078
TI  - [Role of cytokines in beta cell destruction in type 1 diabetes mellitus].

PMID- 12238079
TI  - [Oxidative stress and development of type 1 diabetes].

PMID- 12238080
TI  - [Type 1 diabetes mellitus and immunopathology].

PMID- 12238081
TI  - [An association between type 1 diabetes mellitus and autoimmunity].

PMID- 12238082
TI  - [Slowly progressive IDDM (slowly progressive type 1 diabetes)].

PMID- 12238083
TI  - [Fulminant type 1 diabetes].

PMID- 12238084
TI  - [Pathogenesis of type 2 diabetes mellitus from the viewpoint of clinical
      epidemiology].

PMID- 12238085
TI  - [Epidemiology of diabetes mellitus--chronological change of diabetic population
      and its future].

PMID- 12238086
TI  - [Molecular basis for the development of type 2 diabetes mellitus].

PMID- 12238087
TI  - [Current status of analysis of type 2 diabetes genes].

PMID- 12238088
TI  - [Calpain 10 as a susceptibility gene of type 2 diabetes].

PMID- 12238089
TI  - [Oxidative stress induces cellular damage and dysfunction of pancreatic beta
      cells in type 2 diabetes].

PMID- 12238090
TI  - [Impairment of islet beta-cell metabolism and insulin secretion].

PMID- 12238091
TI  - [Glucose toxicity].

PMID- 12238092
TI  - [Amylin].

PMID- 12238093
TI  - [Glucokinase].

PMID- 12238095
TI  - [Hexokinase].

PMID- 12238094
TI  - [Glucagon-like peptide-1 (GLP-1) receptor].

PMID- 12238096
TI  - [ATP-sensitive K+ channel].

PMID- 12238097
TI  - [Insulin receptor dysfunction and insulin resistance].

PMID- 12238098
TI  - [Polymorphisms in insulin receptor substrate-1 (IRS-1) gene].

PMID- 12238099
TI  - [Beta 3 adrenergic receptor].

PMID- 12238100
TI  - [Historical progress of treatment of diabetes mellitus].

PMID- 12238101
TI  - [Leptin and leptin receptor].

PMID- 12238102
TI  - [Glucose transporter (GLUT4)].

PMID- 12238103
TI  - [Adiponectin as a key molecule of the metabolic syndrome].

PMID- 12238104
TI  - [PPAR family (PPAR alpha, PPAR delta, PPAR gamma)].

PMID- 12238105
TI  - [Uncoupling protein-3 in skeletal muscle].

PMID- 12238106
TI  - [The muscle glycogen synthase].

PMID- 12238107
TI  - [TNF-alpha].

PMID- 12238108
TI  - [Glycoprotein PC-1].

PMID- 12238109
TI  - [High fat diet and lipotoxicity].

PMID- 12238110
TI  - [Insulin resistance induced by drugs, inflammation and stress].

PMID- 12238111
TI  - [Insulin gene mutation].

PMID- 12238112
TI  - [Mutations in the insulin receptor gene].

PMID- 12238113
TI  - [MODY genes].

PMID- 12238114
TI  - [Mutation of amylin (IAPP) gene].

PMID- 12238115
TI  - [The muscle glycogen synthase gene mutation].

PMID- 12238116
TI  - [Diabetes with identified other gene mutations].

PMID- 12238117
TI  - [Secondary diabetes and other specific diseases or drug-induced ones: overview].

PMID- 12238118
TI  - [Impaired glucose metabolism in pancreatic diseases and pancreatic surgery and
      their treatment].

PMID- 12238119
TI  - [Glucose intolerance in pituitary diseases].

PMID- 12238120
TI  - [Glucose intolerance in thyroid diseases].

PMID- 12238122
TI  - [Glucagonoma and glucose intolerance].

PMID- 12238121
TI  - [Carbohydrate metabolism in glucocorticoid excess].

PMID- 12238123
TI  - [Somatostatinoma and glucose intolerance].

PMID- 12238124
TI  - [Glucose intolerance in liver diseases].

PMID- 12238125
TI  - [Changes in cause of death in diabetes].

PMID- 12238126
TI  - [Glucose intolerance in gastrointestinal disease].

PMID- 12238127
TI  - [Glucose intolerance in hemochromatosis].

PMID- 12238128
TI  - [Insulin resistance in myotonic dystrophy].

PMID- 12238129
TI  - [Glucose intolerance in patients with chronic renal failure].

PMID- 12238130
TI  - [Glucose intolerance in visceral fat syndrome].

PMID- 12238131
TI  - [Drug-induced abnormal glucose tolerance].

PMID- 12238132
TI  - [Glucose intolerance induced by interferon therapy].

PMID- 12238133
TI  - [Infection and diabetes mellitus].

PMID- 12238134
TI  - [Genetic syndromes associated with glucose intolerance].

PMID- 12238135
TI  - [WHO implementing national diabetes programs].

PMID- 12238136
TI  - [Biochemical aspects on plasma glucose in vertebrates--with reference to
      trehalose in insects].

PMID- 12238137
TI  - Effects of power frequency alternating magnetic fields on reproduction and pre
      natal development of mice.
AB  - Three groups of ICR male and female mice were exposed to 50-Hz, sinusoidal,
      alternating, horizontal magnetic fields of 0.0 mT (sham), 0.5 mT and 5.0 mT (rms)
      for 9 and 2 weeks prior to mating for males and females, respectively, through
      fertilization and until cesarean sectioning. Fetuses were collected by cesarean
      section on the 18th day of gestation. Approximately half were randomly selected
      for skeletal examination and the remainder used for visceral examination. No
      significant differences were found between the field- and the sham-exposed groups
      in pre-, post- and total implantation losses; number of live fetuses; sex ratio;
      live fetal weight; number of externally abnormal fetuses; and numbers of fetuses
      with skeletal and visceral anomalies. These results suggest that exposure to
      power-frequency magnetic fields has no major effects on reproduction and
      development in mice, and do not support the association of EMF exposure with
      adverse reproductive effects suggested by epidemiology.

PMID- 12238138
TI  - Hepatoprotective and immunomodulatory properties of Tinospora cordifolia in CCl4
      intoxicated mature albino rats.
AB  - Effect of Tinospora cordifolia extract on modulation of hepatoprotective and
      immunostimulatory functions in carbon tetrachloride (CCl4) intoxicated mature
      rats is reported here. Administration of CCl4 (0.7 ml/kg body weight for 7 days)
      produces damage in the liver as evident by estimation of enzymes such as serum
      glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transminase
      (SGPT) and alkaline phosphatase (ALP) as well as serum bilirubin level. CCl4
      administration also causes immunosuppressive effects as indicated by phagocytic
      capacity, chemotactic migration and cell adhesiveness of rat peritoneal
      macrophages. However, treatment with T. cordifolia extract (100 mg/kg body weight
      for 15 days) in CCl4 intoxicated rats was found to protect the liver, as
      indicated by enzyme level in serum. A significant reduction in serum levels of
      SGOT, SGPT, ALP, bilirubin were observed following T. cordifolia treatment during
      CCl4 intoxication. Treatment with T. cordifolia extract also deleted the
      immunosuppressive effect of CCl4, since a significant increment in the functional
      capacities of rat peritoneal macrophages (PM phi) was observed following T.
      cordifolia treatment. The results of our experiment suggest that treatment by T.
      cordifolia extract may be the critical remedy for the adverse effect of CCl4 in
      liver function as well as immune functions.

PMID- 12238139
TI  - Twenty-six week carcinogenicity study of ampicillin in CB6F1-TgrasH2 mice.
AB  - As a part of the ILSI-HESI Alternative to Carcinogenicity Testing (ACT) program,
      we performed a 26-week carcinogenetic study of nonmutagenic drug, ampicillin
      (ABPC) in Tg-rasH2 mice. ABPC was given to Tg-rasH2 mice (0, 350, 1000, 3000
      mg/kg, p.o.) and Non-Tg mice (0, 3000 mg/kg, p.o.) daily for 26 weeks. As a
      positive control, a single dose of MNU was administered once to Tg-rasH2 mice (75
      mg/kg, i.p.). In this study, Tg-rasH2 mice did not demonstrate any increases in
      tumor development in response to ABPC. Thus, ABPC had no carcinogenicity in the
      26-week carcinogenesis study in Tg-rasH2 mice or in a 2-year carcinogenesis study
      in B6C3F1 mice.

PMID- 12238140
TI  - Combination of fixation using PLP fixative and embedding in paraffin by the AMeX
      method is useful for histochemical studies in assessment of immunotoxicity.
AB  - To establish a method for processing lymphoid organs suited to morphological,
      immunohistochemical and enzyme histochemical analyses for assessment of
      immunotoxicity, we examined a combination of fixation with periodate-lysine
      paraformaldehyde (PLP) fixative and embedding in paraffin by the AMeX method (PLP
      AMeX method). Spleen and thymus removed from monkeys and rats were fixed in PLP
      fixative for 6 hours at 4 degrees C. After fixation, specimens were processed and
      embedded in paraffin by the AMeX method. In hematoxylin and eosin-stained
      sections, tissue architecture was well preserved. In immunohistochemical
      staining, markers of T lymphocytes (CD3, CD4, CD8), B lymphocytes (monkey:
      CD20cy, rat: CD45RA) and macrophage (monkey; CD68, rat: ED-1) were well
      identified according to their specificities, although the staining intensity of
      CD8 in the monkey and CD4 in the rat were somewhat weaker in PLP-AMeX-prepared
      sections than in those frozen. In enzyme histochemical staining, alkaline
      phosphatase activity was well preserved in neutrophils. In toluidine blue- and
      Giemsa-stained sections, eosinophil granules and the metachromasia of granules in
      basophil/mast cells were clearly detectable. These findings suggest that the PLP
      AMeX method is a powerful tool for assessment of immunotoxicity.

PMID- 12238141
TI  - Effects of naloxone and post-tetanic stimulation on isolated guinea-pig ileum
      followed by long exposure to morphine and bestatin.
AB  - This study was performed to compare the effects of naloxone (NLX) and post
      tetanic stimulation on isolated guinea-pig ileum followed by prolonged exposure
      to morphine and bestatin. Morphine or bestatin alone did not induce any
      responses. In the presence of 1 microM morphine, the challenge with 1 microM
      naloxone caused quick contraction and post-tetanic contraction. A longer duration
      of these NLX-induced contraction and post-tetanic contractions was observed at
      the 6th stimulation compared to those after the 2nd stimulation. By contrast, the
      addition of bestatin, an aminopeptidase inhibitor, did not induce any NLX-induced
      contraction, although the same results for post-tetanic contraction as those of
      morphine were observed. These different effects of morphine and bestatin on NLX
      induced contraction and post-tetanic contraction in the ileum may be due to
      different mechanisms of action in the opioid system. That in turn may suggest the
      possibility that bestatin has a physical dependence liability.

PMID- 12238142
TI  - Mutagenic activity in roadside soils.
AB  - Mutagenicity of soils sampled at median strips, roadsides and a park neighboring
      arterial roads in Kurume City was determined by Ames test. Organic extracts of
      soils were mutagenic in strains TA98, TA100, YG1041 and YG1042 with and without
      S9mix. No sample showed mutagenic responses in strains YG3003 or YG7108. Extracts
      from soils of median strips and beside intersections showed higher mutagenicity
      and concentrations of PAHs and heavy metals than others, and mutagenic activity
      of soils correlated significantly with concentrations of PAHs and heavy metals.
      However, PAHs accounted for less than 12% of total mutagenicity in strains TA98
      and TA100 of soil extracts. These extracts showed much higher mutagenicity in YG
      strains than in TA strains. The results indicate that these soils may be polluted
      with nitroarenes and aromatic amines.

PMID- 12238143
TI  - In vitro cytotoxicity assay to screen compounds for apoptosis-inducing potential
      on lymphocytes and neutrophils.
AB  - In vitro cytotoxicity assay to screen compounds for apoptosis-inducing potential
      on lymphocytes and neutrophils was investigated. Mouse, rat, dog, and human whole
      blood were incubated for 4 and 6 hr with actinomycin D, camptothecin, cortisone
      acetate, cycloheximide, doxorubicin, etoposide, 5-FU, mitomycin C and puromycin.
      Apoptotic lymphocytes and neutrophils were counted. All test compounds induced in
      vitro apoptosis of lymphocytes and/or neutrophils, but there were different
      potencies among the test compounds and there were also species differences in
      susceptibility. To investigate the in vivo effects of etoposide and cycloheximide
      which induced apoptosis of rat lymphocytes and that of rat lymphocytes and
      neutrophils, respectively, in in vitro assay, rats were intravenously
      administered either etoposide at 12.5, 25 or 50 mg/kg or cycloheximide at 1.25,
      2.5 or 5 mg/kg. Etoposide caused decreases of circulating lymphocytes at 3 hr
      after administration in a dose-dependent manner, -16, -25 and -51%. Although
      cycloheximide caused neither decreased lymphocyte nor neutrophil counts,
      apoptosis in 30% of neutrophils was observed in rats receiving 5 mg/kg at 3 hr
      after administration. Etoposide at 50 mg/kg and cycloheximide at 5 mg/kg caused
      lymphocyte apoptosis in the spleen, thymus, mesenteric lymph nodes, bone marrow,
      and Peyer's patch from 1 to 6 hr after administration, with the maximum changes
      at 3 hr. In addition to apoptosis of these organs, cycloheximide at 5 mg/kg
      caused apoptosis of polymorphonuclear cells in the lamina propria of the small
      intestine. Therefore, it was found that the changes seen in the in vivo
      experiments considerably reflected the changes seen in the in vitro experiments.
      From these results, apoptosis is probably one of the major mechanisms for
      leukocyte toxicity induced by cytotoxic compounds, and the in vitro assay to
      screen compounds for acute apoptosis-inducing potential on lymphocytes and
      neutrophils would be useful as a primary screening method for animal toxicity
      studies. It may also be useful for risk assessments in advance of clinical
      trials.

PMID- 12238144
TI  - Local lymph node assay with non-radioisotope alternative endpoints.
AB  - The local lymph node assay has recently been accepted by regulatory agencies as a
      stand-alone alternate method for predicting allergic contact dermatitis. To
      compare the sensitivity of non-radioisotope methods with that of the standard
      assay, we determined if these modified methods would affect evaluation of
      sensitization potency. For this reason, we used 2,4-dinitrochlorobenzene (DNCB)
      and benzocaine for different sensitizing criteria. Female CBA mice were treated
      for 3 days with a test compound or vehicle applied to each side of both ears.
      Bilateral auricular lymph node proliferative activity was assessed by the
      following endpoints with incorporation of 3H-methyl thymidine (3H-TdR),
      bromodeoxyuridine (BrdU) in vivo, and BrdU ex vivo, IL-2 production, and
      proliferating cell nuclear antigen (PCNA) expression. Ear thickness was also
      tested. The strong sensitizer DNCB was detectable by any of the non-radioisotope
      endpoints as well as by radioisotope-dependent standard assay. On the other hand,
      when evaluating the weak sensitizer benzocaine, significant changes were evident
      in BrdU incorporation ex vivo and in vivo, and IL-2 production. We believe that
      these non-radioisotope methods can assess allergic contact dermatitis caused by
      chemicals even in the laboratory, where it can be difficult to handle
      radioisotopes.

PMID- 12238145
TI  - Comparative articular toxicity of garenoxacin, a novel quinolone antimicrobial
      agent, in juvenile beagle dogs.
AB  - The articular toxicity of garenoxacin (formerly T-3811 or BMS-284756) was
      experimentally examined utilizing juvenile beagle dogs. Garenoxacin and two other
      reference quinolones were administered at intravenous dosages of 30 and 60 mg/kg.
      Each group consisted of 3 male dogs (Experiment I). Oral dosages of 50 mg/kg of 3
      compounds were also given daily to male only and female only groups (Experiment
      II) over a period of 7 days. We evaluated the articular toxicity of garenoxacin
      compared to ciprofloxacin and norfloxacin. In Experiment I, no articular toxicity
      was detected in the 30 mg/kg garenoxacin group. One animal from the 60 mg/kg
      garenoxacin group developed detectable histopathological lesions in the articular
      cartilages of the shoulder, elbow and knee joints. In the 30 mg/kg ciprofloxacin
      group and the 30 and 60 mg/kg norfloxacin groups, histopathological articular
      cartilage lesions of the shoulder, elbow, carpus, hip, knee and tarsus joints
      were observed in all of the dogs. The area under the plasma concentration-time
      curve (AUC0-->infinity) values, after the first dose was administered, for the 30
      mg/kg groups given garenoxacin, ciprofloxacin and norfloxacin were 164, 68.1 and
      65.7 micrograms.hr/mL, respectively. In Experiment II, the degree of
      histopathological change was most significant in the ciprofloxacin group,
      followed by the norfloxacin group, and with comparatively the least changes in
      the garenoxacin group. The AUC0-->infinity values, obtained after the 6th day of
      antimicrobial administration, were 202 and 173 micrograms.hr/mL for male and
      female dogs, respectively, from the 50 mg/kg garenoxacin group. The AUC0-
      >infinity values for the garenoxacin group after the 6th daily administration
      were 7.8 to 17.0 times greater for male dogs and 3.8 to 13.2 times greater for
      female dogs than those obtained from the ciprofloxacin and norfloxacin groups.
      The concentrations of garenoxacin in the synovia, articular cartilage and the
      synovialis 4 hr following the last garenoxacin administration were 2.0 to 6.5
      times higher for male dogs and 1.5 to 3.3 times higher for female dogs than the
      antimicrobial levels measured in the ciprofloxacin and norfloxacin groups. As
      discussed above, although the garenoxacin concentrations in plasma and joint
      tissue were higher than those for ciprofloxacin and norfloxacin, however, the
      articular toxicity of garenoxacin was much less than that of the other two
      antimicrobials.

PMID- 12238146
TI  - Advantages of in vitro cytotoxicity testing by using primary rat hepatocytes in
      comparison with established cell lines.
AB  - We investigated and compared the cytotoxicity of 16 reference compounds in four
      in vitro systems: primary cultured rat hepatocytes, hepatoma HepG2 cell line, non
      hepatic HeLa and Balb/c 3T3 cell lines. After 24 hr of exposure to the test
      compounds, the water-soluble tetrazolium salts WST-1 assay was used as an
      endpoint to evaluate cytotoxicity. Acetaminophen, diclofenac sodium
      cyclophosphamide and disulfiram displayed from 2 to more than 10 times higher
      IC50 values in three cell lines than in rat primary cultured hepatocytes. The
      cytotoxic effects of aspirin, amiodarone, clorfibiric acid, chlorpromazine,
      erythomycin, lithocholic acid, cisplatin and quinidine in rat hepatocytes were
      similar or 2 times stronger than those observed in cell lines. Ketoconazole
      resulted in the lowest IC50 value in the HeLa cell line. The data suggested that
      the compounds which are known to be metabolism-mediated liver toxicants have a
      differential hepatotoxicity in vitro and that primary cultured rat hepatocytes
      could represent a valuable tool for both screening and study of the effects of
      bio-transformation on the cytotoxicity of new chemical entities and xenobiotics
      in vitro.

PMID- 12238147
TI  - [Structural analyses of barbaloin-related compounds in aloe drinks].
AB  - Four kinds of barbaloin (BA)-related compounds (A, B, C, D) in aloe drinks were
      isolated by using preparative HPLC. LC/MS analyses of these compounds showed the
      identical quasimolecular ion peak at m/z 833 [M-H]-. The chemical structures were
      mainly determined by NMR, including 1H-1H two-dimensional correlation
      spectroscopy (COSY), nuclear Overhauser and exchange spectroscopy (NOESY),
      heteronuclear multiple quantum coherence (HMQC), and heteronuclear multiple-bond
      connectivity (HMBC) experiments. They were identified as BA-related compounds A
      (10R, 10"S), B (10S, 10"S), C (10S, 10"R), and D (10R, 10"R) coupled through a C
      10 to C-7' linkage, and newly found in nature. These results suggested that BA is
      converted to dimers during storage of aloe drinks.

PMID- 12238148
TI  - [Contents of barbaloin-related compounds in aloe drinks and their change during
      storage].
AB  - The contents of barbaloin (BA), isoBA, aloin-dimers A, B, C, D and aloe-emodin
      (AE) in aloe drinks were investigated. BA and isoBA were detected in 30 of the 31
      samples at the levels of 120-570 micrograms/mL and 120-580 micrograms/mL,
      respectively. Aloin-dimers A, B, C and D were detected in 8 of the 31 samples at
      the levels of 12-38 micrograms/mL, 13-39 micrograms/mL, 11-36 micrograms/mL and
      16-69 micrograms/mL, respectively. AE was detected in all of the 31 samples at
      the levels of 0.03-1.3 micrograms/mL. When aloe drinks were stored for 4 weeks at
      5 degrees C after opening the bottle, decrease of BA and isoBA, and increase of
      AE and aloin-dimers A, B, C and D were observed in most cases. However, in a few
      aloe drinks, all of BA, isoBA, aloin-dimers A, B, C, D and AE decreased. In these
      drinks, the existence of aloin-trimer was elucidated by LC/MS analyses. These
      data suggested that BA in aloe drinks is converted to the dimer and then to the
      trimer during storage.

PMID- 12238149
TI  - [Identification and determination of unknown chemicals in crops by dual-column GC
      system equipped with MS and ECD].
AB  - A dual-column GC system equipped with MS and ECD, using two identical columns (HP
      1701), one connected to the MS and one to the ECD, has been developed. The
      carrier gas flow rate was adjusted to give the same retention time of each peak
      in both columns. Unknown peaks were detected and identified in 7 samples of crops
      using this system. It was confirmed that the unknown peaks were 5 pesticides,
      i.e., bromopropylate and others. The recoveries and CV of bromopropylate from
      spinach and Komatsuna were good. The results of determination of bromopropylate
      by both MS and ECD were the same. Unknown chemicals can be easily identified
      using GC equipped with MS and ECD, and this system should be useful in the field
      of food hygiene.

PMID- 12238150
TI  - [Simultaneous determination of N-methylcarbamate pesticides and their metabolites
      in agricultural products].
AB  - We investigated the determination of N-methylcarbamate pesticides and their
      metabolites in agricultural products by HPLC with post-column fluorescence
      detection after clean-up with an SPE cartridge. The homogenate of agricultural
      products was extracted with acetone. The crude extract was partitioned between 5%
      sodium chloride solution and dichloromethane, and the dichloromethane layer was
      concentrated to dryness. The residue was dissolved with a mixture of acetone and
      n-hexane, and purified by using Supelclean ENVI-Carb SPE, Bond Elut Extraction
      Cartridge PSA and SAX in series with a mixture of acetone and n-hexane. N
      Methylcarbamate pesticide was analyzed by HPLC with post-column reaction and
      fluoresce detection. N-Methylcarbamate pesticide in citrus fruits and various
      kinds of agricultural products could be analyzed accurately by the presented
      method. Recoveries of N-methylcarbamate pesticides added to several agricultural
      products at the level of 0.10 ppm were mostly in the range of 60-110%. The limit
      of detection was 0.005 ppm.

PMID- 12238151
TI  - A new analytical method for gonyautoxins based on postcolumn HPLC.
AB  - A new ion-pairing high-performance liquid chromatography (HPLC) method on a C30
      column with a volatile mobile phase was developed to separate the gonyautoxin
      group (GTXs) from contaminants, allowing the utilization of liquid
      chromatography/mass spectrometry (LC/MS) with higher performance. A mobile phase
      consisting of 5 mmol/L heptafluorobutyric acid and 2% acetonitrile in 10 mmol/L
      ammonium acetate was adopted for separation of GTXs because the C30 column
      strongly retains GTXs under acidic conditions. The newly adopted method could
      efficiently separate GTXs from contaminants, especially in the toxic short-necked
      clam, whereas the routine HPLC so far used has poor resolution to separate GTXs
      from unknown interfering substances. In our method, GTXs were eluted in the order
      of GTX5, GTX3, GTX4, GTX2 and GTX1 from the C30 column, and were successfully
      determined by sonic spray ionization mass spectrometry (SSI-MS) with high
      sensitivity. This method is characterized by the combination of HPLC using a
      fluorescence detection system for PSP, and SSI-MS for measurement of the mass
      number.

PMID- 12238152
TI  - [Kooroo color: 90-day dietary toxicity study in F344 rats].
AB  - A subchronic toxicity study on kooroo color was conducted using F344 rats of both
      genders. Kooroo color is an extract of yam root, Dioscorea matudai Hayata, of
      which the major components are known to be flavonoid pigments. Use of kooroo as a
      food color is permitted by the Food Sanitation Law in Japan, but the chronic
      toxicity has not been evaluated in the literature. Rats were fed the product of
      kooroo color (PKC) at doses of 0.5%, 1.50%, and 5.0% in basal powder diet, while
      control groups received PKC-free basal diet, for ninety days. A vehicle control
      given propylene glycol (PG) alone, at the same dosage that the 5.0% group
      received, was included, because PKC used in this study contained ca. 80 percent
      PG, used as an extractant during the manufacturing processes. Daily observation
      of general behavior, and weekly measurement of body weight as well as food
      consumption were performed. Hematological, serum biochemical and
      anatomopathological examinations were conducted at the end of administration. No
      abnormalities ascribable to the treatment with PKC or PG were noted in any
      examination in this study. Hence, dietary intake of 5.0% of PKC, i.e., 2,993
      mg/kg/day for males, and 3,376 mg/kg/day for females, as a mean daily intake for
      90 days, had no observable adverse effect in F344 rats. Therefore, kooroo color
      has no significant general toxicity, and its toxicity, if any, is of a very low
      order.

PMID- 12238153
TI  - New estimation methods of bacterial concentration by measuring ATP changes during
      incubation.
AB  - New estimation methods of bacterial cell concentration in samples by measurement
      of the increase in bacterial adenosine-triphosphate (ATP) content during
      incubation using a conventional firefly luminometer were established. When an
      Escherichia coli cell suspension was incubated in nutrient broth, the increase in
      the ATP content of the suspension during the incubation period followed a
      sigmoidal curve. The increase ratio of the ATP content of the suspension at a
      given period of incubation (5 hours in this study) to the initial ATP content was
      greater at higher initial cell concentrations. With this relationship, the
      initial cell concentration of a test suspension could be predicted from the
      measured ratio; this was called the end point method. On the other hand, the lag
      period in the ATP increase curve was longer at lower initial cell concentrations.
      A highly linear relationship was observed between the lag period and the
      logarithm of the initial cell concentrations. Based on this relationship, a delay
      method was developed for prediction. The two relationships were also observed for
      bacterial suspensions of Klebsiella sp., Staphylococcus aureus, Bacillus
      subtilis, and Pseudomonas sp. These results suggested that the two methods have
      the potential to estimate the bacterial cell concentration of a sample
      suspension.

PMID- 12238154
TI  - Flavor production from edible oils and their constituents by Penicillium
      corylophilum.
AB  - Production of volatile substances from edible oils and their constituents by
      Penicillium corylophilum was studied to clarify the mechanism of flavor
      production from a non-stick oil by the organism in a rice cake system. First,
      edible oils from plant and animal origins were tested for flavor production.
      Among the oils tested, coconut oil was the only one from which the flavor was
      produced. Second, triacylglycerols consisting of fatty acids with various lengths
      of carbon chain (C6 to C13) were studied for flavor production. Among the
      triacylglycerols tested, flavors were produced from those consisting of fatty
      acids with carbon chains of C6 to C11. The flavors consisted of methylketones and
      secondary alcohols, whose carbon chains were one carbon shorter than the
      precursor fatty acid molecules of the triacylglycerols. Flavors similar to that
      from the non-stick oil were produced from tricaprylin (C8), trinonanoin (C9), and
      tridecanoin (C10) among the triacylglycerols tested. Formation of mould spores
      was more strongly suppressed by triacylglycerols with shorter chain fatty acids.
      Third, fatty acids with various lengths of carbon chain (C7 to C15) were studied
      for flavor production. Among the fatty acids tested, flavors were produced from
      decanoic (C10) and undecanoic (C11) acids only. The flavors also consisted of
      methylketones and secondary alcohols one carbon shorter than the precursor fatty
      acids. Fatty acids with short carbon chains (C7 to C9) completely inhibited the
      mould growth. Our study showed that the range of carbon chain length of fatty
      acids capable of the flavor production (C10 to C11) was narrower than that of
      triacylglycerols (C6 to C11). It was also found that the non-stick oil and
      coconut oil contain tricaprylin and tridecanoin as triacylglycerols and decanoic
      acid as fatty acid.

PMID- 12238155
TI  - [Colorimetric determination of sulfite in "kanpyo" (dried gourd shavings) and
      "konnyakuseiko" (devil's-tongue fine powder) using sulfite oxidase and catalase].
AB  - A simple and convenient method for colorimetric determination of sulfite in foods
      based on its conversion to formaldehyde with sulfite oxidase and catalase was
      developed. Sulfite in a sample was extracted with water and then diluted with
      methanol. One mL of sample solution containing about 5-10 micrograms of sulfite
      was taken into a test tube with a ground-glass stopper, and 3 mL of 0.04 mol/L
      borate buffer (pH 8.7), 1 mL of 0.4% 3-methyl-2-benzothiazolinone hydrazone
      (MBTH) solution, 2,000 units of catalase solution and 1.0 units of sulfite
      oxidase were added. The mixture was incubated for 35 minutes at 37 degrees C.
      Then 0.15 mL of 1 mol/L hydrochloric acid and 5 mL of 0.2% iron(III) nitrate
      solution were added. The reaction mixture was transferred to a measuring flask
      after standing for 5 minutes at room temperature, and diluted to 20 mL with
      methanol. The absorbance of this solution was measured using a spectrophotometer
      at the wavelength of 635 nm. The calibration curve prepared with sodium sulfite
      showed linearity between 0 to 16 micrograms/mL as sulfur dioxide. The recoveries
      of sulfite in "Kanpyo" (dried gourd shavings) and "Konnyaku-seiko" (devil's
      tongue fine powder) by the proposed method were 97-104%, and the coefficients of
      variation were below 6%. The sulfite values in these foods determined by the
      proposed method were reasonably consistent with those obtained by the bubbling
      distillation-alkaline titration method.

PMID- 12238156
TI  - [Rapid analysis of glufosinate by improving the bulletin method and its
      application to soybean and corn].
AB  - A rapid analytical method for residues of the herbicide glufosinate [DL
      homoalanin-4-yl (methyl)phosphinic acid] and its metabolite (MPPA: 3
      methylphosphinicopropionic acid) in soybeans and corns was developed by improving
      the bulletin method. Fifty mL of solution extracted with water (corresponding to
      2 g of the sample) was loaded on a column packed with 5 mL of anion exchange
      resin, and then the trapped glufosinate and MPPA were eluted with 40 mL of 50%
      acetic acid. After the derivatization of glufosinate and MPPA with trimethyl
      orthoacetate, the derivatives were purified and separated on a silica gel
      cartridge column. The determination of the derivatives was performed with a GC
      FPD. The detection limits for glufosinate and MPPA were 0.01 microgram/g and
      0.005 microgram/g, respectively. The recoveries of glufosinate from soybeans and
      corns were 86.3-92.0%, and those of MPPA were 86.5-95.2%.

PMID- 12238158
TI  - [Influence of the conditions of storage and cooking on growth, invasion and
      survival of Salmonella enteritidis in eggs].
AB  - Basal studies for the confirmation of sanitary rules in the kitchen were
      performed, focusing on preventing an outbreak of food poisoning due to eggs
      contaminated with Salmonella Enteritidis (SE), using hen and quail eggs. SE did
      not grow at 5 degrees C but grew markedly at 25 degrees C in eggs. The invasion
      and growth of SE were marked under very humid conditions regardless of whether
      the eggshell was damaged. The invasion of SE into egg also occurred when eggs
      were taken in and out of the refrigerator. Moreover, SE was spread immediately to
      all non-contaminated eggs when SE-contaminated eggs were cracked into a bowl with
      non-contaminated eggs. In homemade mayonnaise containing 15% vinegar,
      sterilization took several hours to occur. On a stainless-steel bowl, SE survived
      for 2 weeks or more. These findings suggest that it is necessary to pay attention
      to secondary contamination.

PMID- 12238157
TI  - [Study on the detection of prion protein in food products by a competitive enzyme
      linked immunosorbent assay].
AB  - We developed a competitive enzyme-linked immunosorbent assay (ELISA) to detect
      prion protein contained in materials derived from cattle, aiming at establishing
      a method to detect abnormal prion protein (PrPSc) in food products. Rabbit
      polyclonal antibodies were raised against bovine prion peptides. Using these
      antibodies, we have established a competitive ELISA that is capable of detecting
      recombinant bovine prion protein (rBoPrP) in the range of 12 to 1,200 ng and we
      used it to determine prion protein contents in bovine cerebral cortex. This assay
      system was evaluated by spiking food products with various amounts of rBoPrP. The
      determination gave 2-fold higher values in minced meat homogenates and lower
      values in large intestine homogenates than the values expected from the spiked
      amounts. This assay provides a simple determination method of spiked rBoPrP, and
      therefore is expected to be useful for investigating sample pretreatment methods.

PMID- 12238159
TI  - [Levels of phthalates and adipates in processed foods and migration of di
      isononyl adipate from polyvinyl chloride film into foods].
AB  - The levels of dibutyl phthalate (DBP), butylbenzyl phthalate (BBP), di-(2
      ethylhexyl) phthalate (DEPHP), di-isononyl phthalate (DINP), di-(2-ethylhexyl)
      adipate (DEHA) and di-isononyl adipate (DINA) were determined in 50 processed
      foods (ham and sausage, fried dumpling and shao-mai, fish paste products,
      croquette and fried fish, bread, noodle, pickles, etc.). DBP, BBP, DEHP, DINP,
      DEHA, and DINA were contained at nd approximately 47.7, nd approximately 16.6, nd
      approximately 749, nd approximately 358, nd approximately 57.2 and nd
      approximately 20,200 ppb, respectively. High-level contamination of DINA was
      found in fish paste products, croquette and shao-mai, presumably because of
      migration from plasticized wrapping film using for food packaging. We studied the
      relationship between DINA migration from wrapped PVC film into fried croquette
      and its standing time after frying. When the croquette was wrapped immediately
      after frying, the migration from wrapping film into the croquette was highest
      (36,400 ng/g). On wrapping after standing for 5 min and 30 min, the migration
      level was reduced to 1/3.5 and 1/14 of the highest level, respectively.

PMID- 12238160
TI  - [International food standards. (1) What is the Codex Alimentarius Commission?].

PMID- 12238161
TI  - [Potential risk of bovine spongiform encephalopathy (BSE) to human beings and
      therapeutic approaches to prion disease].

PMID- 12238162
TI  - [Anthrax as a biological weapon].

PMID- 12238163
TI  - [Substances eluted from the inner coating of a container can into the food--the
      BADGE issue and and problems with other contaminants].

PMID- 12238164
TI  - [New knowledge about lactose intolerance].

PMID- 12238165
TI  - [Systematic review of the literature--an instrument to capture research results].

PMID- 12238166
TI  - [Atypical depression--an insidious form of severe depression].

PMID- 12238167
TI  - [Sjogren's syndrome and the kidney].

PMID- 12238168
TI  - [Treatment and follow-up of superficial bladder cancer].

PMID- 12238169
TI  - [Viruses and antiviral drug resistance].

PMID- 12238170
TI  - [Factors linked to obesity and body weight perception in adolescents].

PMID- 12238171
TI  - [Cerebral venous thrombosis in a child with ulcerative colitis].

PMID- 12238172
TI  - [Precancerous and malign lesions and the risk of penis carcinoma].

PMID- 12238173
TI  - [Daytime tiredness in a patient with hypertension].

PMID- 12238174
TI  - [Finnish language in medicine-- on history, ideology and practice].

PMID- 12238175
TI  - [Micro-RNAs--a new way to regulate protein synthesis].

PMID- 12238176
TI  - [Celiac disease and female reproductive health].

PMID- 12238177
TI  - [Anemia and radiotherapy].

PMID- 12238178
TI  - [Hypothyroidism, pravastatin therapy and myopathy].

PMID- 12238179
TI  - [Too strenuous exercise?].

PMID- 12238181
TI  - [Privacy protection and epidemiological research].

PMID- 12238180
TI  - [Should university departments have an obligation to stay non-commercial?].

PMID- 12238182
TI  - [The reason why golf is a better hobby than doing register studies].

PMID- 12238183
TI  - [Ethical issues in the control of communicable diseases].

PMID- 12238184
TI  - [Scientist in the jungle of research legislation].

PMID- 12238185
TI  - [Problems with the informed consent].

PMID- 12238186
TI  - [Is placebo without effect?].

PMID- 12238187
TI  - [Recruiting patients to take part in drug trials--problems with the use of
      placebo].

PMID- 12238188
TI  - [Recruiting patients to a drug trial--a researcher's view point].

PMID- 12238189
TI  - [Resuscitation].

PMID- 12238190
TI  - [Do new neurons function in the adult brain?].

PMID- 12238191
TI  - [Breast feeding is not dangerous for mother's bones].

PMID- 12238192
TI  - [Control of the primary tumor--key problem of cancer therapy].

PMID- 12238193
TI  - [The surveillance of gastrointestinal neoplasms after curative surgery].

PMID- 12238194
TI  - [Rectal cancer].

PMID- 12238195
TI  - [Laparoscopic intestinal surgery].

PMID- 12238196
TI  - [Photodynamic therapy of age-related macular degeneration].

PMID- 12238197
TI  - [The Justinianic Plague].

PMID- 12238198
TI  - [Eyes of different colors--a sign of danger].

PMID- 12238199
TI  - [Sudden blindness in a patient with alcoholism].

PMID- 12238200
TI  - [View about the persistence of alexithymia is changing].

PMID- 12238201
TI  - [The importance of racket in the etiology and therapy of tennis elbow].

PMID- 12238202
TI  - [Nest of a hedgehog].

PMID- 12238203
TI  - [Mobile telephones and health, between myth and reality].

PMID- 12238205
TI  - [Gestational diabetes, the necessity for dietetic education].

PMID- 12238206
TI  - [Nursing care strategies for leg ulcers].

PMID- 12238207
TI  - [Which education in nursing knowledge?].

PMID- 12238208
TI  - [From practical knowledge to "knowledge"].

PMID- 12238209
TI  - [Clinical knowledge in action].

PMID- 12238211
TI  - [Inservice training in the transmission of practice knowledge].

PMID- 12238212
TI  - [When knowledge becomes competence].

PMID- 12238213
TI  - [Knowledge transmission, a nursing competence to develop].

PMID- 12238214
TI  - [Nursing knowledge, a concrete reality].

PMID- 12238215
TI  - [Nursing knowledge, assimilation and use in practice by a student].

PMID- 12238216
TI  - [Hospitals, shortages and vacations].

PMID- 12238217
TI  - [Debate on expertise at the ANFIIDE congress].

PMID- 12238220
TI  - Immunization still critical to Canadian public health.

PMID- 12238218
TI  - [Ambulatory management, a new challenge in oncology].

PMID- 12238221
TI  - Writing a successful research proposal.

PMID- 12238222
TI  - Nurses' experiences with Web-based learning.

PMID- 12238223
TI  - Fun therapy. Humour in the hospital.

PMID- 12238224
TI  - Physicians' perceptions of nurse practitioners.
AB  - Because the successful implementation and integration of the NP role are partly
      contingent on support from physicians, nursing needs to educate physicians.
      Physicians need greater exposure to the role to increase physician awareness and
      ultimately increase support.

PMID- 12238225
TI  - Thanks to Jesse.

PMID- 12238226
TI  - Defining nurses' role in health informatics.

PMID- 12238227
TI  - Who shall care for the children of the poor and uninsured? Pediatric dentistry in
      the United States.
AB  - Although Medicaid was established at least in part to help alleviate dental
      problems for children of the indigent, the program has not been particularly
      successful. Some possible solutions to the problem of disparities in access to
      pediatric dental care are suggested, including access and workforce approaches.
      Whatever approaches are undertaken, cost-benefit analyses should be done to
      demonstrate economic value.

PMID- 12238228
TI  - Turnover of certified nursing assistants: a major problem for long-term care
      facilities.
AB  - The increasing number of aging Americans who will need long-term care, coupled
      with the need to keep this care affordable, represents a formidable challenge to
      the healthcare system. Some response must be made to address what will soon
      become immediate need. A significant part of the approach to this problem lies in
      making long-term care as efficient, cost effective, and affordable as possible.
      Reducing turnover of certified nursing assistants (CNAs) will help achieve these
      goals. This article discusses the extent, implications, and causes of this
      turnover and puts forth a program to correct the problem.

PMID- 12238229
TI  - Wellness programs: a remedy for reducing healthcare costs.
AB  - Offering wellness programs has become a popular method for preserving the health
      of employees in the hope of generating lower healthcare expenses and, in turn,
      higher profits. This article offers a cost/benefits analysis of providing
      wellness programs, to determine whether such programs could add value to a
      company. Recommendations follow for how to implement a successful wellness
      program with minimal initial costs should an analysis find that wellness
      initiatives would prove beneficial.

PMID- 12238230
TI  - Fifteen years of Nexus--a 21st century retrospective.

PMID- 12238231
TI  - Hubris and the undoing of American medicine.

PMID- 12238232
TI  - Development of a healthcare quality improvement measurement tool: results of a
      content validity study.
AB  - Current methods of measuring continuous quality improvement (CQI) implementation
      are too long and not comprehensive. A new survey for CQI implementation was
      developed and tested for content validity using a panel of 8 experts--7 from the
      United States and 1 from England. The survey was reduced from 70 items to 22. The
      resultant survey had a clarity interrater agreement (IR) of .91, a
      representativeness IR of .93, a clarity content validity index (CVI) of .73, and
      a representativeness CVI of .91. Content validity served as an excellent data
      reduction method in building a valid, concise, and comprehensive measure of CQI
      implementation.

PMID- 12238233
TI  - Research, CME, media relations boost diabetes center's profile.
AB  - For Boston's Joslin Diabetes Center, media relations rather than formal
      advertising is the key to a high-profile image. The communications office targets
      newspaper, magazine and TV reporters and editors with public service
      announcements and news about research and clinical care advances. Other
      successful tools include a high-end quarterly magazine, a fact-filled information
      kit, disease-specific support programs and a catalog of educational materials.

PMID- 12238234
TI  - Mini-medical school enhances hospital's stature in market area.
AB  - There is a waiting list for each eight-week session of the "Mini-Medical School"
      run by Baystate Medical Center in Springfield, Mass. The program offers classes
      on medical subjects to the general public. Its goal is to bring together
      physicians and people of the community. The faculty members, who hold teaching
      appointments at Tufts University School of Medicine in Boston, are as
      enthusiastic about the program as their students.

PMID- 12238235
TI  - Ohio's Parma Community General Hospital celebrates 40 years. Independence, growth
      featured as themes.
AB  - Parma Community General Hospital in Parma, Ohio, is called "the only successful
      independent community hospital in Cuyahoga County." It celebrated its 40th
      anniversary in 2001 by touting impressive statistics, such as growing to 339 beds
      now from 200 beds in 1962. Events to celebrate the anniversary included an
      employee celebration, the opening of a residential hospice center and a community
      prayer breakfast.

PMID- 12238236
TI  - Historic Washington, D.C., hospital reopens in new $96 million facility. The
      George Washington University Hospital attracts fanfare.
AB  - A diverse gathering of political leaders, entertainment and sports personalities
      and government officials attended the grand opening ceremony of George Washington
      University Hospital's brand-new 371-bed hospital building in Washington, D.C. The
      new facility was introduced to the Washington community by a series of tours for
      the media, physicians, nurses, hospital employees and their families.

PMID- 12238237
TI  - UMMC recruitment plan succeeds. Multi-disciplinary approach aligned to overall
      marketing strategy.
AB  - At the University of Maryland Medical Center (UMMC), Baltimore, a team of
      marketing, human resources and patient care services departments staffers worked
      on a campaign to recruit staff members. They created a successful campaign that
      exceeded by 12% the four-month goal for new hires. Reportedly, the program has
      had lasting momentum and has helped to enhance the image of UMMC. Incidentally,
      the campaign also won peer recognition for its creators.

PMID- 12238238
TI  - Hospital Web site 'tops' in Louisiana. Hospital PR, marketing group cites East
      Jefferson General Hospital.
AB  - East Jefferson General Hospital in Metairie, La., launched a new Web site in
      October 2001. Its user-friendly home page offers links to hospital services,
      medical staff, and employer information. Its jobline is a powerful tool for
      recruitment. The site was awarded the 2002 Pelican Award for Best Consumer Web
      site by the Louisiana Society for Hospital Public Relations & Marketing.

PMID- 12238239
TI  - The 'first' instead of the 'oldest'. St. John's Riverside, in Yonkers, N.Y.,
      markets its history.
AB  - St. John's Riverside Hospital, Yonkers, N.Y., built an integrated campaign upon
      its long history. Using billboards, print ads, bus shelters, radio and TV it
      touted its 130-plus years and its long history of firsts. Its integrated campaign
      proclaimed these "firsts." It specifically targeted its marketing to middle to
      upper-middle income residents of the surrounding area, particularly females
      between ages 25 and 54.

PMID- 12238240
TI  - Pharmacological characterization of the nitrergic innervation of the stomach.
AB  - Proximal gastric relaxation is a vago-vagal reflex upon food intake. The efferent
      neurons involved at the level of the stomach are nonadrenergic noncholinergic.
      Deficient proximal gastric relaxation is observed in a portion of patients with
      functional dyspepsia, while exaggerated relaxation might contribute to the
      development of gastroesophageal reflux disease via triggering of transient lower
      esophageal sphincter relaxations. Nitric oxide (NO) is mediating, together with
      vasoactive intestinal polypeptide (VIP) as parallel cotransmitter, the
      nonadrenergic noncholinergic neurotransmission of the proximal stomach. Evidence
      for a sequential link between VIP as neurotransmitter and muscular NO generation
      was obtained when studied in isolated gastric smooth muscle cells; inducible NO
      synthase seems expressed. The endogenous gastric nitrergic neurotransmitter is
      not sensitive to superoxide anion generators and NO scavengers, that reduce the
      relaxation to exogenous NO. This is not due to the release of a nerve-derived
      hyperpolarizing factor in addition of NO, nor to binding to thiols, but Cu/Zn
      superoxide dismutase is involved in the protection of endogenous NO versus
      superoxide anions and scavenging. The release of NO from gastric nitrergic
      neurons is not sensitive to negative feedback but is inhibited via presynaptic
      alpha 2-adrenoceptors. Nitric oxide functionally antagonizes acetylcholine in the
      smooth muscle cells but does not influence the release of acetylcholine at the
      cholinergic varicosities. Stimulating or inhibiting the gastric nitrergic neurons
      might be a target for drug therapy in functional dyspepsia or gastro-esophageal
      reflux, respectively.

PMID- 12238241
TI  - Endocrinology in intensive care medicine: new insights and therapeutic
      consequences.
AB  - Sepsis, excessive inflammation, multiple organ failure and weakness prolong the
      need for intensive care in critically ill patients. Furthermore, the risk of
      death is high in the prolonged critically ill patient (20% after two weeks and
      30% after 3 weeks). In prolonged critical illness, protein hypercatabolism and
      relative preservation of adipose tissue with fatty infiltration of vital organ
      systems is present. In view of the crucial role of the hypothalamus-pituitary
      axis for metabolic homeostasis, we have studied this endocrine organ in the
      context of critical illness. The initial "adaptive" neuroendocrine response to
      critical illness illness consists primarily of activated anterior pituitary
      function. In the chronic phase of critical illness, a uniformly reduced pulsatile
      secretion of anterior pituitary hormones has been observed, whereby impaired
      function of target organs. A reduced availability of thyrotropin (TSH)-releasing
      hormone (TRH), gonadotropin (LH)-releasing hormone (GnRH), the endogenous ligand
      of the growth hormone (GH)-releasing peptide (GHRP) receptor (ghrelin) and, in
      very long-stay critically ill men also of GH-releasing hormone (GHRH),
      inferrentially appears involved. Pulsatile secretion of GH, TSH and LH can be re
      amplified by relevant combinations of releasing factors which also substantially
      increases circulating levels of insulin-like growth factor (IGF)-I, GH-dependent
      IGF-binding proteins, thyroxine (T4), triiodothyronine (T3) and testosterone.
      Anabolism is only evoked when GH-secretagogues, TRH and GnRH are administered
      together whereas the effect of single hormone treatment is minor and accompanied
      by side effects. A remarkable observation was that a high serum concentration of
      IGF-binding protein 1 predicts death in the ICU. This observation challenged the
      classical dogma of adaptive hyperglycemia during critical illness. In a large
      prospective randomized clinical study (1548 patients), we showed that ICU
      mortality was reduced by 42% with strict normalization of glycemia using
      exogenous insulin infusion (N Engl J Med 2001). This was due to prevention of
      typical ICU complications such as sepsis, multiple organ failure and need for
      prolonged invasive organ support and intensive care. We conclude that the new
      concept of reduced stimulation of pituitary function in prolonged critically ill
      patients opens new therapeutic perspectives to reverse the paradoxical 'wasting
      syndrome' but that maintenance of strict normoglycemia with insulin is crucial to
      also increase the chances of survival of these patients.

PMID- 12238242
TI  - [Androgens and increased lipogenesis in prostate cancer. Cell biologic and
      clinical perspectives].
AB  - A search for novel and biologically relevant androgen-regulated genes and
      processes in the human prostate led to the intriguing observation that androgens
      provoke a remarkable and coordinated increase in the expression of several genes
      involved in triglyceride and cholesterol synthesis in various prostatic
      adenocarcinoma cell lines. This coordinated activation was shown to be the result
      of a novel and indirect pathway in which androgens cause activation of a
      secondary transcription regulator, Sterol Regulatory Element Binding Protein
      (SREBP), a pivotal factor in the control of intracellular lipid homeostasis. The
      biological relevance of increased lipogenesis in the biology of prostate cancer
      is underlined by recent immunocytochemical investigations on needle biopsies
      showing an increase in the expression of Fatty Acid Synthase (FAS) in 94% of the
      tumor-lesions examined. This increase is already evident in the earliest
      recognizable lesions (Prostatic Intra-epithelial Neoplasia; PIN) and is more
      pronounced in tumors with a higher Gleason score, suggesting that increased FAS
      expression may serve both as an early tumor marker and as a marker of tumor
      progression. As in tumor cell-lines, increased FAS expression in prostate tumors
      seems to be only part of a more general and coordinated activation of lipogenic
      pathways. Further studies revealed that lipogenesis in prostate tumor cells can
      be enhanced not only by androgens but also by growth factors and by tumor
      associated disturbances in signal transduction pathways. EGF, for instance, is
      also able to activate lipogenesis via the SREBP pathway and activation of the P13
      kinase system by inactivation of PTEN (a phenomenon observed in some 50% of the
      prostate cancers) also causes increased lipogenesis. The early and nearly
      universal activation of lipogenesis in prostate cancers (and also in various
      other tumors) suggests that this may be a fundamental event in the development of
      the tumoral phenotype, an element that certainly merits further investigation. In
      addition, there are serious indications that interference with enhanced lipogenic
      activity in tumor cells may cause tumor cell death and delayed tumor development,
      suggesting that increased lipogenic activity in tumor cells may open a novel
      avenue for therapeutic intervention.

PMID- 12238243
TI  - The role of growth factors, angiogenic enzymes and apoptosis in
      neovascularization and tumor growth-collected publications.
AB  - Hemangiomas represent the most frequent tumors of infancy. However, the
      pathogenesis of these tumors is still largely unknown, and current treatment of
      juvenile hemangiomas remains unsatisfactory. We have presented a novel animal
      model for hemangiomas. Induction of hemangioma development was achieved by
      intraperitoneal (i.p.) infection of 4-day-old rats with the mouse polyoma virus
      (PyV). This led to the development of multiple hemangiomas, which caused death of
      the untreated animals within 3 weeks p.i. The hemangiomas had the histological
      and immunohistochemical features reminiscent of human hemangiomas. Moreover, the
      angiogenesis inhibitor TNP-470 afforded a protective effect in this model. Tumor
      growth is determined by the balance between cell proliferation and apoptosis and
      is modulated by angiogenesis. Angiogenesis is a complex process, involving
      extensive interplay between cells, extracellular matrix components and soluble
      factors. Each of these factors represents a possible target for pharmacological
      intervention to inhibit blood vessel formation and subsequently tumor growth. We
      have focused on specific inhibitors of the angiogenesis inducers basic fibroblast
      growth factor and Thymidine Phosphorylase and studied their mechanism of action
      and anti-angiogenic activity. In addition, we have shown that the apoptosis
      inducer cidofovir inhibits PyV-induced hemangioma development in rats and the
      growth of virus-independent, vascular tumors in mice. So far, cidofovir has only
      been evaluated clinically for the treatment of human papillomavirus (HPV)
      associated tumors. Our findings open new perspectives for the use of cidofovir as
      an anti-tumor agent in the therapy of hemangiomas and other tumors that are not
      associated with an oncogenic virus.

PMID- 12238244
TI  - [Aldosterone and cardiovascular diseases, more than water and salt retention].
AB  - The activation of the different neurohumoral system plays an important role in
      the different mechanisms of the development and progression of arterial
      hypertension and chronic heart failure. The renin-angiotensin II-aldosterone
      system is one of the key players in this process. With the use of ACE-inhibitors
      in the treatment of hypertension and heart failure, less attention has been paid
      to aldosterone. Aldosterone has been only considered as a humoral factor playing
      a role in salt and water homeostasis and as a consequence controlling arterial
      blood pressure. There is now evidence of vascular synthesis of aldosterone
      besides the secretion at the adrenal cortex as well that aldosterone is involved
      in the development of left ventricular hypertrophy in arterial hypertension,
      decreased arterial elasticity of the large arteries in chronic heart failure and
      is inversely correlated with venous capacitance in chronic heart failure.
      Moreover aldosterone plays a role in the disturbances of the vascular matrix,
      endothelial dysfunction as well as baroreflex dysfunction. This work has
      contributed indirectly in the unraveling of the mechanisms which could be partly
      explained the results of the RALES-trial. The new research project will be
      focused on the study of the cross-talk between the autonomic nervous system and
      aldosterone in normotension, arterial hypertension and heart failure.

PMID- 12238245
TI  - Pathological gambling. A comprehensive review.
AB  - Due to recent changes of gambling laws, accessibility to gambling has become more
      widespread and thus, there has also been an increase in the prevalence of
      pathological gambling (PG). The wide range of social, economic, and psychological
      problems associated with PG are well known. There is a need for better
      understanding of PG and this review attempts to do so. Literature searches using
      the Medline and PsycINFO databases were used. Critical examining of the
      literature showed that familial/genetic, sociological, and individual factors
      (e.g., an individual's personality, biochemistry, psychological states, and
      cognitions) are implicated in the development and maintenance of PG, yet at
      present, the evidences are not solid. Similarly, there have been a lot of
      theories for PG but again, none of them are solid enough to provide a clear
      understanding of PG. Recent psychological-based theories seem to provide some
      solid ground for further research. We highlight four areas for future
      consideration for research. (1) Most studies have generalized findings from one
      form of gambling to another. It is suggested that it is now not tenable to
      consider gambling as a single phenomenon that can explain all forms of gambling.
      (2) Almost all of the studies in the gambling literature are Western-based and
      the results are often generalized to other ethnic and cultural groups. There is
      now an urgent need to close this gap. (3) Future studies need to address
      methodological problems in the current gambling/PG literature. (4) Almost all of
      the gambling literature has focused on the issue of why people start gambling. It
      is suggested that looking at variables as to why people stop gambling in a single
      episode may be a more fruitful area of research then why people start gambling.
      This is because what motivates one to continue gambling, despite losses in a
      session and across sessions, is a characteristic that distinguishes nonproblem
      gamblers from problem gamblers and pathological gamblers (PGs).

PMID- 12238246
TI  - Origins and consequences of child neglect in substance abuse families.
AB  - The empirical literature pertaining to the prevalence, origins, and consequences
      of neglectful parenting as it relates to substance abuse is critically reviewed.
      Available evidence indicates that children who experience parental neglect, with
      or without parental alcohol or drug abuse, are at high risk for substance use
      disorder (SUD). The effects of parental substance abuse on substance abuse
      outcome of their children appear to be partly mediated by their neglectful
      parenting. The discussion concludes with presentation of a developmental
      multifactorial model in which neglect, in conjunction with other individual and
      environmental factors, can be integratively investigated to quantify the child's
      overall liability across successive stages of development as well as to map the
      trajectory toward good and poor outcomes.

PMID- 12238247
TI  - Silence as communication in psychodynamic psychotherapy.
AB  - Moments of silence in the therapy hour, on the part of the client or therapist,
      can communicate important psychodynamic information, as well as deeply facilitate
      the therapeutic encounter. The client may be communicating emotional and
      relational messages of need and meaning. The therapist can use silence to
      communicate safety, understanding and containment. However, if this intervention
      is not skillfully and sensitively employed by the practitioner, the client may
      feel the therapist's quietness as distance, disinterest, and disengagement,
      leading to breaches in the trust and safety of the therapeutic alliance.

PMID- 12238248
TI  - Self-focused attention in social phobia and social anxiety.
AB  - Self-focused attention is an awareness of self-referent information and is
      present in many emotional disorders. This review concentrates on the role of self
      focused attention in social anxiety with particular reference to the Clark and
      Wells [Clark, D. M., & Wells, A. (1995). A cognitive model of social phobia. In
      R. R. G. Heimberg, M. Liebowitz, D. A. Hope, & S. Scheier (Eds.), Social phobia:
      diagnosis, assessment and treatment. New York: Guilford.] model of social phobia.
      According to Clark and Wells, self-focused attention is an important maintaining
      factor in the disorder because it increases access to negative thoughts and
      feelings, can interfere with performance, and prevents the individual from
      observing external information that might disconfirm his or her fears. Clark and
      Wells also propose that socially phobic individuals construct a distorted
      impression of themselves, based on internally generated information, that takes
      the form of a visual image (often seen from the perspective of an observer) or
      felt sense. This paper describes the model and then reviews other theories of
      self-focused attention, and empirical evidence on self-focused attention. Two
      types of evidence are reviewed: one, studies that have been conducted from a
      variety of theoretical perspectives that have relevance either to social anxiety
      in general or to the Clark and Wells model in particular; two, studies that were
      designed as a direct test of Clark and Wells' predictions. The final section of
      the review summarizes the conclusions and suggests areas for future examination.

PMID- 12238249
TI  - Psychological aspects of tinnitus and the application of cognitive-behavioral
      therapy.
AB  - This article presents an overview of tinnitus (ringing or buzzing in the ears),
      its psychological effects, and the application of cognitive-behavioral therapy
      (CBT) for its treatment. Several studies have confirmed an association between
      psychological factors, such as anxiety and depression, and severe tinnitus and
      preliminary reports suggest that a proportion of tinnitus patients suffer from
      mental illness. Assessment strategies used in CBT for tinnitus include structured
      interviews, daily diary ratings, and validated self-report questionnaires. The
      treatment approach described in this article includes applied relaxation, imagery
      and distraction techniques, advice regarding environmental sounds, management of
      sleep, cognitive restructuring of thoughts and beliefs associated with tinnitus,
      and relapse prevention. The literature pertinent to CBT approaches to treating
      tinnitus is reviewed, and it is concluded that CBT shows promise as a treatment
      of tinnitus-related distress. Future research directions are discussed.

PMID- 12238250
TI  - Biased attentional behavior in childhood anxiety. A review of theory and current
      empirical investigation.
AB  - This review examines the state of current theory and research regarding a
      relatively new area of study in childhood anxiety: the examination of attentional
      biases associated with the processing of threatening environmental stimuli. In
      particular, this paper focuses upon current attempts to extend an information
      processing framework traditionally associated with childhood psychopathology
      (i.e., Crick & Dodge [Psychol Bull 115 (1994) 74]) and anxiety-related
      attentional bias research previously conducted only with adults, to populations
      of anxious children. First, a thorough discussion of Crick and Dodge's model and
      its applicability to current theories of anxiety is presented. Although each
      stage of Crick and Dodge's model is shown to possess correlates with current
      conceptualizations of anxiety, the research investigations reviewed here focus
      upon the multiple approaches that have been undertaken to better comprehend
      anxious children's attentional biases in encoding and subsequent task performance
      decrements. Specifically, recent investigations of anxious children's attentional
      performance utilizing Stroop tasks, probe detection tasks, and the relatively new
      probe localization task are reviewed. A discussion of the disparate findings
      associated with recent studies of each of these tasks is given, with an eye
      toward the need to specify the developmental, theoretical, demographic, and
      clinically relevant characteristics associated with the biased attentional
      behavior observed among highly anxious children.

PMID- 12238251
TI  - [Mosaic phenotypes].
AB  - 1) Mosaicism results from the mutation in part of somatic cells after the
      fertilization, only a few cases occur due to mutation during meiosis. Mosaicism
      is characterized by genetic or functional difference of two or more cell lines in
      one individual from one zygote. 2) Phenotypical variety is high and depends on
      the proportion of cell lines of individual clones. 3) Clinical prognosis of
      mosaic individuum is better in comparison to the full mutation in all cells. 4)
      The genetic prognosis of reproduction in relatives of the mosaic individuum is
      without increased recurrent risk, genetic prognosis of own offspring depends on
      the moment of mutation occurrence--wheit occurs before day 16 to 20 when gonadal
      cells are differentiated, it represents high risk of transmission. 5) Diagnosis
      of mixoploids in some cases requests investigation of different cells
      (fibroblasts, lymphocytes). 6) Clinical "signal" features of the mosaic are
      hemihypertrophy, asymmetry, Blaschko lines, pigmentations. 7) Risk of malignant
      tumor is increased, similarly to other chromosomal aberrations, chromosomal
      instability or hamartomatoses. 8) Mosaics of gene mutation have usually normal
      mental development and are manifested by external abnormalities only. 9)
      Incidence of mosaic phenotypes is high and therefore the diagnosis of mixoploids
      and gene mosaic is important for the estimation of clinical as well as genetic
      prognosis.

PMID- 12238252
TI  - [Interstitial pulmonary processes].
AB  - New classification of the idiopathic interstitial pneumonias on the basis of the
      structural characteristics is presented. The contemporary classification includes
      four types of disease, differing in the clinical symptomatology, reaction to
      therapy and prognosis.

PMID- 12238253
TI  - [Tuberculosis in the Czech Republic in the year 2000].
AB  - BACKGROUND: Incidence of tuberculosis (TB) in the Czech Republic (CR) during the
      year 2000 was evaluated on the basis of newly detected cases as well the
      restriction of known TB sources by antituberculosis treatment. Data from
      compulsory reported TB cases in the TB register for the year 2000 were used as
      well as data from the analysis of treatment in cohorts of patients reported
      quarterly in 1999 and evaluated 12 months later. METHODS AND RESULTS: 1442 cases
      of new diseases and TB relapses were reported in 2000 (14.1/100,00). 1244 cases
      (12.1/100,000) were TB of the respiratory system, 198 cases (2.0/100,000)
      belonged to the extra-respiratory TB. 61.9% of cases were bacteriologically
      verified TB of the respiratory system. In comparison with the year 1999, the
      number of TB cases was lower by 11.7%, respectively by 9.3% in TB of the
      respiratory system. The positive trend in TB incidence recorded in CR since 1998
      has continued. From 1442 cases of the TB, 916 were males (63.5%) and 526 females
      (36.5%). Majority of patients was older than 65 years. 143 (9.9%) of TB cases
      were patients born extra CR ("foreigners"), namely coming from Ukraine (41),
      Vietnam (16), and Romania (14). 74 patients died of tuberculosis, mostly those
      older than 65 years. The youngest was the 24-year-old Ukrainian and a 38 year old
      homeless person, the citizen of CR. The highest incidence of TB was in West
      Bohemia, in Prague and in North Moravia; the lowest incidence was in South
      Moravia and in South Bohemia. TB was identified because of patient's troubles
      (68.0%), in the risk groups (13.3%), and by examination of contact persons
      (4.7%). Other mycobacteriosis than TB was identified in 92 patients. The
      treatment was evaluated in 606 persons with the pulmonary TB, which was
      bacteriologically verified; analysis was done in cohorts of patients reported
      quarterly in 1999. 70.1 to 77.5% of patients in individual cohorts were
      successfully treated, in 3 patients the treatment failed and 9 patients
      interrupted the treatment. Remaining 25% of patients either died before or during
      the treatment. The high mortality rate resulted from the high age and other
      diseases in some of the patients. CONCLUSIONS: WHO includes CR between countries
      with low TB incidence. Within the stabile population of CR the continuous
      decrease of TB incidence should continue, unless some unfavourable effects occur.

PMID- 12238254
TI  - [Relation between levels of acute phase proteins and copper and the parameters of
      systolic and diastolic left ventricular function in patients with chronic heart
      failure].
AB  - BACKGROUND: Acute phase protein concentrations and serum copper levels in
      patients in acute phase of myocardial infarction were significantly higher in
      subjects with heart failure compared to patients with non-complicated course of
      myocardial infarction. Acute phase protein concentrations correlated with the
      parameters of the left ventricular systolic function in patients in acute phase
      of myocardial infarction. The aim of the study was to evaluate the relation of
      acute phase protein concentrations and serum copper levels with the parameters of
      left ventricular systolic and diastolic function in patients with chronic heart
      failure out of the acute phase post myocardial infarction. METHODS AND RESULTS:
      Authors analysed relation between the acute phase proteins, C-reactive protein,
      fibrinogen, and copper concentrations and the left ventricular systolic and
      diastolic function assessed by echocardiography in 38 patients (26 men and 12
      women, average age 68 years) with chronic heart failure and advanced left
      ventricular systolic dysfunction post myocardial infarction with ejection
      fraction lower or equal to 35%. Serum C-reactive protein concentrations
      correlated significantly with the left ventricular ejection fraction (r = -0.38,
      p < 0.05) and with isovolumic relaxation time IRVT (r = -0.51, p < 0.001)-
      inverse correlation. C-reactive protein concentration correlated with the ratio
      of the maximal flow velocity of the early transmitral diastolic filling (E vave)
      and with the maximal transmitral flow velocity during atrial contraction (A wave)
      -E/A ration (r = 0.43, p < 0.01). C-reactive protein concentration also
      correlated with the ration of the time velocity integrals of the E wave and the A
      wave--TVIE/TVIA (r = 0.45, p < 0.01)--positive correlation. Correlation between
      the fibrinogen and copper concentrations and the left ventricular ejection, or
      that with parameters of the diastolic left ventricular function were not
      statistically significant. CONCLUSIONS: Study revealed significant correlation
      between C-reactive protein concentration and parameters of the left ventricular
      systolic and diastolic function in patients with chronic heart failure post
      myocardial infarction. Correlation between copper and fibrinogen levels and
      parameters of the left ventricular function was not significant.

PMID- 12238255
TI  - [Transplantation of life-preserving organs at the Institute of Clinical and
      Experimental Medicine (IKEM)].

PMID- 12238256
TI  - [Personal experience with the surgical treatment of thoracic outlet syndrome].
AB  - The authors describe their experience with surgery of suspected TOS (8 cases) and
      traumatic TOS after clavicular fracture (1 case) in the last 2 years. In the
      group there were 7 women and 2 men aged 39-59 years with a history from 6 months
      to 26 years. Seven patients reported complete or almost complete relief of
      symptoms. In one case we observed progressive deterioration during 6 weeks
      postoperatively. All patients underwent decompression of the brachial plexus and
      subclavian artery from a supraclavicular approach. There was one case of
      reoperation after 15 years after primary surgery.

PMID- 12238257
TI  - [Video-assisted myocardial revascularization and left-sided minithoracotomy using
      the Symmetry automatic connector].
AB  - OBJECTIVE: Introduction of the new method of videoassisted multiple direct
      revascularization of the heart muscle from left-sided minithoracotomy (LAST--Left
      Anterior Small Thoracotomy) using an automatic connector of central anastomoses
      Symmetry (St. Jude Medical ATG, Inc., St. Paul, MN) in patients indicated for re
      operation of bypasses of the coronary arteries or with pathological conditions of
      the sternum and for the cosmetic effect of submammary incisions in women. METHOD:
      From September 2001 to the end of February 2002 15 patients with affections of
      three arteries had an operation from a LAST approach with videoscopic
      construction of central anastomoses by means of a Symmetry connector with portal
      entries and the use of extracorporeal circulation introduced from the groin
      without cardioplegic arrest. Nine men and six women were operated with a mean age
      of 68.7 years and a mean ejection fraction (EF) of 58.2%. In seven instances
      reoperation of aortocoronary bypasses was involved; two patients with multiple
      myelomas (morbus Kahler) had a brittle and cavernously altered sternum, all six
      women wanted a small skin incision below the breast. The criterion for ruling out
      the mentioned procedure was marked atherosclerotic affection of the ascendent
      aorta, affection of the arteries in the aortoiliac area and affection of one or
      two coronary arteries suitable for miniinvasive revascularization without
      extracorporeal circulation. Fourteen patients had an angiographic check up
      examination of the patency of grafts before they were discharged. RESULTS: The
      total number of distal anastomoses per patient was 3.13 +/- 0.6, the median
      period of extracorporeal circulation was 112 +/- 34 minutes and the mean time of
      operation 186 +/- 52 minutes. Blood losses were on average 425 ml/24 h without
      necessity of revision on account of haemorrhage. Eleven (73%) patients were
      subjected to an ultra fast track protocol with extubation on the operating table.
      The mean time spent in the postoperative department was 8.6 hours and the total
      hospitalization period 5.5 days. None of the operated patients died. Peroperative
      ischaemia of the heart muscle was not observed, in one instance the authors
      observed a newly developed atrial fibrillation. During an angiographic check-up
      the authors detected 6 (13.6%) stenoses and occlusions in 44 checked bridged
      vessels. CONCLUSION: The alternative approach reduces the risk of cardiac injury
      during reoperation and the danger of impaired healing of the sternotomical wound
      in patients with pathological conditions of the sternum, with contamination of
      the surrounding tissue (e.g. in tracheostomy) or malignant disease. The cosmetic
      effect of the submammary incision, the small inguinal incision and endoscopic
      saphenous vein harvesting should be considered in elective direct
      revascularization of the heart muscle in women. Bridging of the coronary arteries
      with optical assistance from minithoracotomy and with an automatic connector of
      central anastomoses seems to be a safe alternative of standard sternotomy only
      with methodological but not anatomical or functional restriction.

PMID- 12238258
TI  - [Intrapericardial rupture of the inferior vena cava caused by blunt trauma].
AB  - A thirty-years-old man with pectus excavatum was unconscious, in shock and with a
      history of blunt trauma of the chest and epigastrium admitted to hospital. After
      a short time he developed signs of pericardial and peritoneal effusion with
      tamponade and circulatory failure. Urgent laparotomy and sternotomy was
      performed. We found approximately a 5 cm long rupture of the right atrium,
      anterior wall of the intrapericardial part of the vena cava inferior with short
      extension to the infradiaphragmatic part of the vena cava inferior. We controlled
      bleeding by hand and by application of a Satinsky partial vascular clamp. Final
      plastic correction of the rupture was performed by implantation of a native
      autologous pericardial flap. After a complicated postoperative course the patient
      was discharged on the 37th postoperative day. Seven months after surgery the
      patient is in a good condition and has no signs of stenosis at the place of
      correction.

PMID- 12238259
TI  - [Is a bioprosthesis with a rigid stent a good choice for aortic valve replacement
      in elderly patients?].
AB  - BACKGROUND: Either stented or stentless bioprostheses can be used for aortic
      valve replacement (AVR) in aged patients. However the choice of the valve type
      remains controversial. The implantation technique of the stentless valves is more
      complex but the haemodynamic performance supposed to be superficial to the
      stented ones. The aim of the study was to review our experience with stented
      bioprostheses implanted in the last year. MATERIAL AND METHODS: The study reviews
      retrospectively 35 patients who underwent AVR with Biocor fy St Jude Medical from
      May 2000 to May 2001. The mean age was 73 years (65-81). Associated procedures
      were CABG in 17, aortoplasty in 3 and Bentall procedure in 1. Thirty-two patients
      had aortic stenosis, the mean preoperative gradient was 44.2 mmHg. Nineteen
      implanted valves were 23 mm and smaller in diameter. All patients were examined
      by a cardiologist (including ECHO) one month after surgery. RESULTS: There was no
      early mortality (30 days) and no sign of structural valve deterioration or valve
      thrombosis. Mean hospital stay was 10.2 days (5-30). Mean postoperative gradient
      one month after surgery was 14.1 mmHg (6-24). CONCLUSIONS: The AVR with a stented
      bioprosthesis is a standard procedure with excellent results, the postoperative
      gradient is comparable to the gradient of the stentless valves.

PMID- 12238260
TI  - [Infiltration of subcutaneous tissue for prevention of blood loss in extensive
      plastic surgery operations--10 years' experience].
AB  - The authors emphasize the importance of extensive preoperative infiltration of
      subcutaneous tissue in some selected plastic operations as prevention of major
      blood losses and reduction of the number of blood transfusions during operation
      and the postoperative period.

PMID- 12238261
TI  - [Surgical treatment of intervertebral disk herniation and spondylosis in
      degenerative diseases of the thoracic vertebrae--basic approach. Review of the
      literature and a group of 12 patients].
AB  - Prolapse of an intervertebral disc and neurologically important spondylosis of
      the thoracic vertebrae are not a frequent finding--in the wide spectrum of
      surgical treatment of degenerative diseases of the spine the numbers of
      operations in the thoracic section account only for a few percent. The authors
      give an account of 12 patients treated surgically during the 5-year period 1997
      2001 at the Neurosurgical Department of the First Medical Faculty Charles
      University and Institute for Postgraduate Training in Prague-Stresovice. They
      describe the establishment of the neurological finding from the differential
      diagnostic aspect, the algorithm of radiological examination and selected
      treatment. In the group of surgically treated patients were two with spinal and
      radicular symptoms, 8 patients had only spinal and 2 patients had only root
      symptoms. Laminectomy was performed in one female patient, in 9 patients
      discectomy was performed from a transpedicular approach and in two patients
      discectomy from costotransversectomy. Complete normalization of clinical
      complaints was recorded in 2 patients, in 8 the condition improved and 2 patients
      did not improve. In 2 patients a revision was made and extension of the approach
      on account of persisting clinical complaints, in one patient after revision
      complete normalization of the clinical finding occurred, the second patient did
      not improve after revision. Selection and results of the surgical approach--in
      all instances different types of posterior approach were involved--are discussed.
      In the discussion also a brief review, indications and illustrations of posterior
      approaches are given. The discussion deals also with the advantages and
      disadvantages of the method as compared with the anterior approach or endoscopic
      technique. The authors emphasize the advantages of the microsurgical technique-
      the open posterior approach still holds an irreplaceable place in the spectrum of
      surgical therapeutic methods despite the onset of endoscopic methods.

PMID- 12238262
TI  - [Treatment of redislocated fragments of long bones using plaster cast wedging].
AB  - The authors wish to remind of the advantages of an old conservative therapeutic
      method used in redislocated long bone fractures--cast wedging, Gipskeilung. This
      mode of treatment makes it possible to restore axial as well as planar
      dislocation and it is used in corrections of redislocated fractures of the leg
      and is applied during the last 3 years also in the treatment of fractures of the
      forearm in children. In 1997-2000 this procedure was used for treatment at the
      Clinic of Paediatric Surgery, Orthopaedics and Traumatology, 33 children aged 3
      16 years, with a redislocated fracture of the leg, 21 children aged 3-16 years,
      mean age 9.8 years, and with a redislocated fracture of the forearm 12 children
      aged 5-15 years, mean age 10.2 years. In no instance this treatment failed or was
      associated with serious complications. According to experience with our group of
      patients a method is involved which in correct indications holds a justified
      place in treatment of fractures of the leg and forearm in traumatology of child
      an adolescent age.

PMID- 12238263
TI  - [Effect of drug therapy on lower urinary tract symptoms indicating the presence
      of benign prostatic hyperplasia in transurethral resection of the prostate].
AB  - OBJECTIVE: Medical therapy of lower urinary tract symptoms (LUTS) suggestive of
      benign prostatic hyperplasia (BPH) has fundamentally changed. The aim of the
      study is to verify the suggestion that the medical therapy delayed the need of
      operative treatment and led to changes in characteristics of patients in need of
      surgery, or whether it had possibly caused deterioration of the results of
      surgery. MATERIAL AND METHODS: A group of 137 patients treated by TURP in 1991
      (before medical therapy was introduced in Slovakia) was compared with a group of
      122 patients treated by TURP in 2001 when medical therapy was offered as the
      primary initial therapy. We evaluated the patient's age, co-morbidity, type and
      length of medical therapy of LUTS, indications for operation, the weight of the
      resected tissue, the length of urinary bladder drainage after the operation and
      the period of hospitalisation. RESULTS: Patients in 2001 were on average 3.1
      years older (p = 0.007), co-morbidity was present in 68.6% patients in 1991
      compared to 85.2% in 2001 (not significant), and TURP for objective indications
      was done in 58.4% of patients in 1991 and in 50% in 2001. In 2001 71 out of 122
      (58.2%) patients received medical therapy and 30 of them (24.6%) were operated on
      for objective indications. The weight of the resected tissue was 20.2 +/- 13.2
      grams in 1991 and 24.6 +/- 15.4 grams in 2001 (p = 0.027). In 1991 the catheter
      was removed 4.5 +/- 1.8 days after the operation compared to 3.1 +/- 2.2 days in
      2001 (p = 0.0001). The duration hospitalisation in 1991 was 7.7 +/- 5.7 days
      compared to 5.2 +/- 3.2 in 2001 (p = 0.0001). CONCLUSIONS: Patients receiving
      medical therapy have surgery at a higher age. The higher age of patients was not
      related to co-morbidity or the increased number of operations for objective
      indications, nor did the complications during surgery increase. On average more
      of the prostatic tissue was removed and the period of hospitalisation was
      shorter.

PMID- 12238264
TI  - [Critical infusion incident caused by incorrect use of a patient-controlled
      analgesia pump].
AB  - We report on the case of a 17-year-old male patient who received a PCA pump after
      nephrectomy for postoperative analgesia. The syringe of the PCA pump was filled
      with 50 mg morphine and positioned about 25 cm above the heart. Since the piston
      of the syringe was not bolted while the pump was switched off, an unnoticed
      accidental evacuation of the whole content of the syringe into the intravenous
      line of the patient occurred because of gravity. This problem exists not only
      with PCA pumps, but can happen with syringe pumps in general. The incident, which
      can only be explained by strongly reduced venous pressure, was detected by
      chance. No harm resulted for the patient, but under different conditions it could
      have been lethal. This critical incident was caused by various factors: incorrect
      application in combination with insufficient experience or training, stress,
      inadequate handing-over of the patient and a lack of arrangements and
      instructions for procedures in routine situations. Suggestions for preventing
      such dangerous critical incidents are made and discussed. In particular, an
      algorithm for the correct procedure when inserting or changing the syringe of a
      syringe pump is presented.

PMID- 12238265
TI  - [Quantitative assessment of neuromuscular block of the orbicularis oculi muscle].
AB  - In a prospective clinical study neuromuscular block at the orbicular ocular
      muscle was examined qualitatively and quantitatively by an AMG approach. The
      signals were recorded, visualized and evaluated simultaneously under PC-support
      after TOF-stimulation in 20 s intervals. Fifty ASA I and II patients were
      included into the study. After oral premedication with midazolam 10-15 mg,
      anaesthesia was induced with propofol 2 mg/kg and alfentanil 0.02 mg/kg and
      maintained by means of propofol 6-8 mg/kg/h and alfentanil 0.02 mg/kg/h. After
      intubation and signal stabilization, mivacurium 0.75 mg/kg was administered and
      neuromuscular blockade was recorded online. The measured acceleration at the
      orbicular ocular muscle amounted 0.9 g on average. Maximal neuromuscular block
      was registered at 78.5% and the TOF-ratio of 0.8 was achieved after 14.1 min. The
      low values of the AMG-signals of the orbicular ocular muscle requiring very high
      technical demands on the measuring instrument. Additional problems arise through
      the considerable temporal expenditure for discovering the optimal location of
      stimulation. During the AMG monitoring the position dependence of the measured
      values of the sensors must be taken into consideration. These technical problems
      restrict the suitability of the AMG at the orbicular ocular muscle as a
      quantitative neuromuscular monitoring tool.

PMID- 12238266
TI  - [Cis-atracurium--an equivalent substitution for atracurium in pediatric
      anesthesia?].
AB  - Cis-atracurium is a stereoisomer of atracurium, about five times more potent than
      the racemate. Whereas cis-atracurium is routinely used in adults, its effects on
      children are still poorly defined. We compared equipotent doses of atracurium and
      cis-atracurium in children aged between 2 and 12 years regarding the quality of
      neuromuscular blockade, the intubation conditions and the occurrence of side
      effects. After approval by the ethics committee and with informed parental
      consent, 84 children (ASA I or ASA II) were randomly allocated to receive either
      0.5 mg/kg atracurium (group A, n = 42) or 0.1 mg/kg cis-atracurium (group C, n =
      42). In both groups anaesthesia was induced with 15 micrograms/kg alfentanil and
      5-7 mg/kg thiopentone. We assessed the intubation conditions according to the
      Krieg Scale. Anaesthesia was maintained with a nitrous oxide/oxygen mixture of
      2:1 and isoflurane in an endexpiratory concentration of approximately 0.6 Vol.%.
      Neuromuscular blockade was controlled acceleromyographically in response to
      supramaximal stimulation of the ulnar nerve. We measured the onset time (T1 =
      5%), duration of effect (T1 = 25%), recovery index (T1 = 25%-75%) and the
      recovery time at a train-of-four-ratio (T4/T1) of 0.7. These parameters did not
      show any significant differences between group A and group C: onset time: 3.1 +/-
      1.5 min (group A) versus 3.4 +/- 1.1 min (group C), duration of effect: 34.1 +/-
      5.5 min (group A) versus 34.1 +/- 6.5 min (group C), recovery index: 9.3 +/- 3.3
      min (group A) versus 9.6 +/- 2.5 min (group C), recovery time at a TOF-ratio of
      0.7:49.3 +/- 8.4 min (group A) versus 52.3 +/- 6.6 min (group C). In group A, the
      intubation conditions were "excellent" or "good" in 98% of the patients, whereas
      in group C the figure was only 69%. Regarding side-effects, we found
      significantly more frequent urticaria in group A (6 of the 42 patients) (p < or =
      0.05) than in group C, in which no patient showed urticaria. Flush and
      tachycardia occurred much less frequently and there were no significant
      differences in the two groups: two patients in group A and only one in group C.
      The authors conclude that atracurium and cis-atracurium lead to comparable
      neuromuscular effects in children aged between 2 and 12 years. Only the
      intubation conditions were better after atracurium, but atracurium was followed
      by urticaria more often than cis-atracurium.

PMID- 12238267
TI  - [Evaluation of emergency medicine knowledge and procedures after finishing the
      course "resuscitation specialty"].
AB  - Emergency medical services are an indispensable part of out-patient medical care.
      For this purpose, special qualifications are necessary and these are taught
      within the framework of a course entitled "Certificate for Emergency Medical
      Services". These courses are organized either as a block course, that is a one
      week course, or as weekend courses in progression. These two types of courses are
      compared here. Three block courses with 546 participants and five weekend courses
      with 599 participants were examined. The practical examination took the form of
      four practice stages, with 95 people from the courses taking the examination. The
      examination focussed on certain areas such as ECG diagnostics in the case of
      cardiac arrest, early defibrillation, removing helmets, immobilizing a fractured
      tibia, respiration with emergency equipment, vein punctures and volume
      substitution. Of the doctors attending the courses, 59.7% were residents, 35.7%
      were senior house officers and 4.6% were specialists or general practitioners.
      Thirty-nine (or 41.1%) of those examined attended a block course and 56 (58.9%)
      weekend courses. In diagnosing cardiac arrest, those attending a block course
      were more reliable (92.3% diagnosed correctly, compared with 67.9% in the other
      group). Fifteen per cent from both groups were not able to correctly diagnose
      ventricular fibrillation from the ECG. Of the block course participants, 39.1%
      chose defibrillation with the correct energy, compared with 24.2% of those
      attending weekend courses. One out of two participants recognized a deliberate
      fault in the ECG equipment. Thirty-seven per cent of participants of the block
      course and 35.9% from the weekend courses failed to choose the right size splint
      for neck immobilization. Regarding respiration, 67.2% of participants of the
      block course group and 71.4% of the weekend course group carried out manual
      artificial respiration. When using respirator equipment, 90% from the block
      course and 72.2% of the other group noticed an increase in respiratory tract
      pressure. When giving artificial respiration to an infant, 51.9% of the weekend
      course group and 35.9% of the block course group used an unsuitable emergency
      respirator. When choosing a central puncture point most participants picked the
      external jugular vein and gave their own previous experience as the reason (block
      course 48.2%, others 52.1%). Accuracy regarding the volume requirements in the
      case of large-scale burns, as well as choosing the quantity (16.7% compared with
      7.4%) and the correct solution (47.9% compared with 40.7%) was unsatisfactory.
      For these reasons, we strongly recommend intensifying training in block courses
      for the future qualification of doctors in emergency services. It would also be
      useful to conduct an oral exam at the end of the entire course, which could also
      entitle candidates to use this professional designation as one of their
      qualifications.

PMID- 12238268
TI  - [Should precocious hyperthyroidism be treated early?].

PMID- 12238269
TI  - [Questioning HRT].

PMID- 12238271
TI  - [Digestive malacoplakia].
AB  - INTRODUCTION: Malacoplakia, a chronic granulomatous disease, rarely involves the
      digestive tube and, when it does, takes on a pseudotumoral aspect. OBSERVATION: A
      37 year-old man was hospitalized for chronic diarrhea that had progressed over 15
      years. He exhibited an edematous-ascitic syndrome and bilateral pleurisy together
      with, biologically, a malabsorption syndrome. The endoscopic examinations
      (fibroscopy and colonoscopy) revealed polypoid tumor-like formations. An image of
      tumoral stenosis of the sigmoid-colic junction was revealed on barite lavage.
      Histological examination of the surgical sample (wide left colectomy of one third
      of the transverse) was suggestive of malacoplakia (histiocytes with
      characteristic Michaelis-Gutmann bodies). DISCUSSION: Malacoplakia is an
      inflammatory disease predominantly affecting the urogenital tract. Other organs
      can be involved. Its clinical symptomatology is highly disparate. The interest of
      this disease is in its pathogenesis, on which, in fact, its treatment is based.

PMID- 12238270
TI  - [Typhoid fever. Retrospective study of 52 cases in Lebanon].
AB  - OBJECTIVE: Present the epidemiology and clinical characteristics of typhoid fever
      in the Lebanon. METHODS: Retrospective study of 52 patients admitted to a
      university hospital center between 1995 and 1999. The criteria for inclusion were
      a positive Salmonella typhi or paratyphi hemoculture and/or Widal serodiagnosis >
      1/160 for O agglutinin, in the presence of evocative symptoms. RESULTS: The
      patients were aged a mean of 31 +/- 24 years. The mean duration between the onset
      of fever and diagnosis was of 10 +/- 8 days. Fever was observed in 96% of cases
      and the other predominant symptoms were diarrhea (37%), abdominal pain (31%) and
      headache (29%). Feverish gastroenteritis is a frequent manifestation in children
      (61% of cases). Complications were noted in 33% of cases and were predominantly
      digestive. Leukopenia is not a good diagnostic marker. S. typhi was the cause in
      83% of cases. Resistance to ampicillin was noted in 13% of cases, to
      cotrimoxazole and to chloramphenicol in 10% and to ofloxacine in 3% of cases. One
      death was reported (2%) of an immunodepressed patient. CONCLUSION: Typhoid fever
      is still an endemic disease in the Lebanon and should be systematically evoked in
      the case of prolonged fever, feverish gastroenteritis and/or headache. The
      appearance of bacteria resistant to antibiotics makes ceftriaxone or
      ciprofloxacine the empirical treatment of choice.

PMID- 12238272
TI  - [Necessity of postpartum serologic screening for congenital toxoplasmosis in
      women who are seronegative at the end of pregnancy].

PMID- 12238273
TI  - [Kikuchi-Fujimoto's disease concurrent with a primary Herpes simplex type 1
      infection].

PMID- 12238274
TI  - [Primitive group A streptococcal peritonitis].

PMID- 12238275
TI  - [Herpes zoster of the maxillary branch of the trigeminal nerve].

PMID- 12238276
TI  - [Cholesterol crystal embolism disease, diagnostic criteria].
AB  - FROM AN EPIDEMIOLOGICAL POINT OF VIEW: With the aging of the population and
      increased indications for angioplasty or anticoagulant therapy, the incidence of
      cholesterol crystal embolism is going to increase. FROM A CLINICAL POINT OF VIEW:
      A systemic disease related to multiorgan distal ischemia, cholesterol crystal
      embolism has multiple facets. Rapidly progressive renal failure, malignant
      hypertension in the elderly, mesenteric ischemia, acute pulmonary edema,
      cutaneous ischemia or encephalopathy symptomatology may reveal cholesterol
      crystal embolism. THE IMPORTANCE OF DIAGNOSIS: The occurrence of such symptoms in
      poly-vascular patients, notably following exposure to inductive factors such as
      arterial catheterism, anticoagulant therapy or cardiac or vascular surgery is
      highly suggestive of the diagnosis. The lack of its knowledge can lead to
      inappropriate anticoagulant therapy and useless arteriography, which may even
      prolong or worsen cholesterol crystal embolism.

PMID- 12238277
TI  - [Which therapeutic regimen for eradicating Helicobacter pylori and cicatrization
      of a duodenal ulcer. Is there a role for short-term treatment?].
AB  - CURRENT REGIMENS: The regimen recommended for the eradication of Helicobacter
      pylori and cicatrization of a duodenal ulcer is the association, for 7 days, of a
      double-dose of gastric anti-secretory drug and 2 antibiotics, followed by a usual
      dose of an anti-secretory for a further 3 weeks. During randomized studies, this
      therapeutic regimen led to an eradication rate of 80 to 90%. However, in current
      practice in France, the eradication rate is of only 60 to 75%. THE QUESTIONS
      RAISED: Phenomena of resistance to antibiotics are not the only cause. Lack of
      compliance is frequent, partly generated by poor tolerance to the antibiotherapy.
      Many recently published studies have provided elements of response to several
      questions concerning the eradication of Helicobacter pylori: can one reduce the
      duration of treatment by associating a triple antibiotherapy or, to the contrary,
      should one prolong treatment to be sure that patients fully comply to the 7 days
      of treatment? Should the dose of anti-secretory drug be doubled? And, with regard
      to cicatrizing the duodenal ulcer: can one reduce the duration of the anti
      secretory agent? WITH THE RESULTS OF RECENTLY PUBLISHED CLINICAL TRIALS: It is
      legitimate today to prescribe double antibiotherapy for 10 to 14 days, associated
      with a double dose of an anti-secretory, without having to prolong the anti
      secretory after this initial period, in order to cicatrize the duodenal ulcer.
      Further studies will specify the optimal duration between 10 and 14 days.
      However, till now, this therapeutic regimen for eradicating Helicobacter pylori
      and cicatrizing a duodenal ulcer has not obtained marketing authorization and is
      not appropriate for treating gastric ulcers and for complicated (notably
      hemorrhagic) gastroduodenal lesions.

PMID- 12238278
TI  - [Age-related macular degeneration].
AB  - EPIDEMIOLOGICAL AND PATHOGENIC DATA: Age-related macular degeneration (ARMD) is
      the first cause of blindness in industrialized countries in patients over the age
      of 55. Its prevalence increases with age, affecting up to 25% of the population
      aged over 75. The pathogenesis of this disease is not well known. Not only aging,
      but also other varying degrees of genetic and environmental factors are implied.
      CLINICAL ASPECTS: Precursors (first clinical signs of ARMD) can be observed on
      examination of the fundus: drusen (localized deposits of lipids and lipoproteins)
      and alterations in retinal pigment epithelium (RPE) (hypo- or hyperpigmentation).
      Two forms of complications are observed: atrophic (or "dry") and exudative (or
      "wet"). The atrophic form is defined by the presence of degeneration in the
      central RPE, choriocapillaris and photoreceptors, resulting from the enlargement
      and/or coalescence of small areas of peri-foveolar atrophy (or "geographic"
      atrophy). The exudative form, responsible for the majority of cases of blindness
      due to ARMD, is characterized by the appearance of choroidal new vessels,
      identifiable on fluorescein angiography and responsible for serous retinal
      detachment, edema and hemorrhage, leading to the destruction of the macular
      photoreceptors. FROM A THERAPEUTIC POINT OF VIEW: Treatment of the atrophic form
      is currently only palliative (visual aids and re-habilitation of low vision).
      Treatments of the exudative form having demonstrated their efficacy are laser
      photocoagulation and dynamic phototherapy with verteporfine, providing relative
      stabilization of visual acuity in around 2/3 of the eyes. Other treatments are
      under evaluation: anti-angiogenic treatments, surgical techniques (ablation of
      the new vessels, foveal translocation), new laser treatments (transpupillary
      thermotherapy, selective photocoagulation of the feeder vessels). Photoreceptor
      and pigment epithelium transplantations or implantation of microphotodiodes
      represent other long-term alternatives.

PMID- 12238279
TI  - [Biomedical research, development of legislative provisions].

PMID- 12238280
TI  - Splanchnic circulation and metabolism in patients with acute liver failure.
AB  - Acute liver failure is associated with mortality of around 50%. The aim of the
      present studies was to examine the circulatory and metabolic state of the
      splanchnic region in acute liver failure. This had not been studied previously
      and it could be expected that improved understanding of the pathophysiology of
      acute liver failure could lead to improved therapy. Hepatic plasma flow was
      estimated in patients with acute liver failure after development of hepatic
      encephalopathy grade III, by the use of liver vein catheterization and continuous
      infusion of sorbitol. The method was evaluated against the prerequisites of
      Fick's principle. Hepatic plasma flow could be estimated with sorbitol but not in
      all patients and the standard error of the estimated hepatic blood flow was
      higher than in other patient groups. In 20 patients with acute liver failure,
      mean hepatic blood flow was increased. At the same time, the systemic and the
      peripheral hemodynamics were examined. The ratio hepatic blood flow/cardiac
      output was increased in many patients. Lower extremity blood flow was within
      normal limits. Thus, low systemic vascular resistance index in acute liver
      failure was likely to be a consequence of vasodilatation in the muscular
      resistance vessels and, in particular, in the splanchnic resistance vessels.
      Intervention with high-volume plasmapheresis changed systemic and splanchnic
      hemodynamics differently, suggesting that the splanchnic vasodilatation in liver
      failure may by caused by a specific mechanism different from the one that leads
      to peripheral vasodilatation. Infusion of dopamine increased mean arterial
      pressure, cardiac output, and hepatic blood flow in acute liver failure. The
      splanchnic exchange of substrates for oxidative metabolism was examined.
      Splanchnic oxygen consumption was increased. The ratio splanchnic oxygen
      consumption/systemic oxygen consumption indicated that 1/3 of the oxygen used in
      the whole body in acute liver failure was used in the splanchnic region. The
      splanchnic metabolism of fuel substrates was abnormal. Lactate and pyruvate was
      released and there were no detectable gradients of free fatty acids or of the sum
      of amino acids. There was a small release of ketone bodies. The data suggested
      that the energy needs of the failing liver was covered by intracellular fat. The
      hypothesis of splanchnic tissue hypoxia was examined from different approaches.
      The normal hepatic venous oxygen saturation, the splanchnic release of both
      lactate and pyruvate, and a normal hepatic venous pyruvate/lactate ratio in the
      presence of low acetoacetate/hydroxybutyrate ratio rather indicated high
      substrate turnover than splanchnic tissue hypoxia. Amino acid and ammonia
      metabolism was examined. It was observed that arterial ammonia concentration
      measured after institution of mechanical ventilation was associated with cerebral
      herniation 1-5 days later. The background for hyperammonemia was that ammonia was
      released from the splanchnic circulation. The data implied that glutamine was
      deamidated in the gut and alanine and ammonia was released into the portal vein
      as during normal circumstances. Then due to severely decreased hepatic function
      the liver was unable to remove ammonia and alanine as it normally would. Further,
      the data implied that urea synthesis was impaired. Exchange of ammonia in muscle
      tissue was studied in 7 patients with acute liver failure and muscle tissue seems
      to play a major role in ammonia detoxification in acute liver failure. Treatment
      with high-volume plasmapheresis decreased arterial ammonia, which was likely due
      to increased urea production or stimulation of glutamine synthesis in muscle
      tissue. These findings add to our understanding of the pathophysiology and have
      implications for the management of acute liver failure.

PMID- 12238281
TI  - On the etiology of anal squamous carcinoma.
AB  - The thesis is based on 13 publications in English and a review of the literature.
      The underlying work was done with the overall aim to describe incidence patterns
      for anal squamous carcinoma (anal SC) and to contribute new insight into the
      causes of this neoplasm. The work, supported by the Danish Cancer Society, was
      carried out in the period 1991-2000 while I was employed at 1) the Danish Cancer
      Registry, 2) Statens Serum Institute, Department of Epidemiology Research, and 3)
      the National Cancer Institute, Viral Epidemiology Branch, Maryland. Study designs
      employed include a ) population-based incidence studies in Denmark and the United
      States, b) register-based case-control studies and cohort studies for the
      scrutiny of multiple cancer patterns among patients with anal SC and for the
      study of anal SC risk among individuals with certain non-malignant diseases of
      the anal region as well as among persons with the acquired immuno-deficiency
      syndrome (AIDS), c) a nationwide interview-based case-control study of risk
      factors for anal SC and in Denmark and Sweden, and d) a combined molecular
      biological and histological analysis examining the association of human
      papillomavirus (HPV) status with histopathological and anatomical characteristics
      in anal SC tissues. The epidemiology of anal SC has changed remarkably during the
      second half of the 20th century. In Denmark, age-adjusted incidence rates per
      100,000 person-years increased during the period 1943-1997 from around 0.2 among
      both men an women to 0.5 among men and 1.0 among women. Where systematically
      studied, incidence rates of anal SC have also been found to increase in a few
      other countries (Sweden and the United States). Register-based multiple cancer
      studies have shown an excess of previous and subsequent genital cancers of
      squamous histology among women with anal SC. This is likely to reflect common
      susceptibility toward infection with cancer-associated HPV types shared by all
      anogenital organs covered by squamous epithelium. A study based on data from the
      United States supports the possible role of anogenital SC-associated HPV types in
      the development of some tonsillar cancers. Observations in other register-based
      investigations and in the Danish-Swedish case-control study challenge the long
      held belief that benign anal lesions (e.g. hemorrhoids) and anal inflammation
      (e.g. in association with Crohn's disease) are linked to an increased risk of
      anal SC. The work documents strong links between a variety of sexual behavior
      measures and the risk of anal SC. The previously observed excess of anal SC among
      homosexual men is confirmed. Unlike in previous studies, an increased risk of
      anal SC associated with promiscuous heterosexual activity is also documented
      among both men and women. Measures of sexual extroversion, rather than sexual
      preference, are linked to the risk of anal SC presumably by means of higher rates
      of anal HPV infection in people with such behaviors. A new hypothesis is proposed
      to explain how smoking, the only consistently observed non-sexual risk factor in
      previous studies, might be associated with anal SC risk. A study of the short
      term cancer profile among 309.365 AIDS patients in the United States provided no
      evidence to support immunosuppression as a major risk factor for anal SC in the
      first two years after the AIDS diagnosis. With the introduction around 1996 of
      highly active anti-retroviral therapy regimens, however, the future may hold a
      para-doxical increase in the incidence of anal SC along with the increased life
      expectancy in this population. Examination of tumor tissues from patients in
      Denmark and Sweden by the polymerase chain reaction techique showed a high
      proportion of anal SCs to be positive for types of HPV that are associated with
      high risk of cervical cancer (90%, 100%, and 58% among women, homosexual men, and
      heterosexual men, respectively). Tumor tissues from control subjects with
      adenocarcinoma of the rectum were consistently HPV-negative. A combined molecular
      biological and histological analysis showed that anal SCs with likely origin in
      the anal canal are 7.5 times more likely to be HPV-positive than anal SCs with
      likely origin in the perianal skin. Additionally, cancer of the anal canal are
      more likely than those of the perianal skin to be characterized histologically by
      small or medium-sized tumor cells, basaloid features, and little or no
      keratinization. Epidemiological studies from the past two decades have
      contributed imprtantly to our current understanding of anal SC and its causes.
      Most cases of this neoplasm can now be considered as a consequence of sexually or
      otherwise acquired infection in the anal mucosa with types of HPV already known
      to be involved in cancers of the uterine cervix. Expectedly, the upward trend in
      the incidence of anal SC seen over the past half century will continue in many
      years to come. However, there is currently widespread, yet cautious, optimism
      regarding the prospects for a prophylactic HPV vaccine. It this optimism is
      justified, the future may bring drastic reductions in the incidence of HPV
      associated morbidities, including SC.

PMID- 12238282
TI  - Platelet function and fibrinolytic activity in borderline and mild hypertension.
      The influence of age, exercise, smoking and antihypertensive therapy.

PMID- 12238283
TI  - Evaluation of some techniques for measurements of lung function in young
      children.

PMID- 12238284
TI  - Postoperative wound infection: indicator of clinical quality?
AB  - INTRODUCTION: This study aims to gain experience with continuous electronic
      registration of data regarding postoperative wound infection following heart
      surgery. METHODOLOGY: Every patient undergoing cardiac surgery from February 1999
      to May 1999 was included in a prospective study and followed for 30 days. Data
      regarding type of operation, development of postoperative wound infection, risk
      factors for wound infection and a risk stratification were submitted
      electronically to a central database. RESULTS: All 180 operations were registered
      in the database, and risk variables were registered for all patients but one
      (99.4%). A spot test comprising 32% of 131 operations registered at the time of
      the spot test, showed a predictive value of a correctly applied diagnosis of
      wound infection at 78%. Only 4/7 (57%) of infections in the spot test were
      registered in the database. All deep wound infections were registered during the
      study period. CONCLUSION: Data, including risk stratification, in relation to
      postoperative wound infection following heart surgery can be registered
      continuously in a central database. Registration of all wound infections,
      however, requires several resources and may be incomplete. The present
      registration's good level of cover concerning deep wound infection and risk
      variables indicates, that deep wound infection may provide a meaningful indicator
      of clinical quality, although good risk variables still need to be developed.

PMID- 12238285
TI  - Prolonged parenteral nutrition after neonatal gastrointestinal surgery. A Danish
      experience.
AB  - INTRODUCTION: Long-term treatment with parenteral nutrition (PN) may be essential
      for survival in infants after neonatal gastrointestinal surgery. It seemed well
      indicated in a population-based study to estimate the need for long-term PN and
      to characterize the infants that received TPN with regard to diagnosis and
      clinical course. METHODOLOGY: This study reviews the clinical course of infants
      with gastrointestinal disease (gastroschisis, intestinal atresia, omphalocele,
      volvulus, Hirschsprung's disease and necrotizing enterocolitis) with a prolonged
      need for parenteral nutrition in the Western part of Denmark over a period of 11
      1/2 years. RESULTS: A total of 21 patients with need for PN for 55 days or more
      due to gastrointestinal disease were registered with a cumulative hospital stay
      of 4462 days. The study showed a low incidence of long-term PN due to gastro
      intestinal surgical illness with an incidence of approx 6.1 per 10(5) births per
      year. Gastroschisis and intestinal atresia were the most common primary
      diagnoses. Two groups of patients were identified: 1) six infants with short gut
      syndrome caused by major resections or atresia of the small intestine (less than
      50 cm intestine) and 2) a larger group (n = 15) with no or only minor resection
      of the small bowel. The former group had a significantly longer hospital stay and
      a longer need for PN. The incidence of short bowel syndrome including six infants
      was 1.7 per 10(5) births per year. CONCLUSIONS: Prolonged need for PN in infants
      operated for gastrointestinal disease was registered at a low frequency in the
      Western part of Denmark, most frequently caused by gastroschisis and intestinal
      atresia. The clinical course was characterized by repetitive problems of catheter
      replacements and septic episodes. The mortality due to conditions related to the
      gastrointestinal disease was 14% (3/21).

PMID- 12238286
TI  - Rule of law, law and the health profession. Zimbabwe 2002.
AB  - INTRODUCTION: Politically motivated violence around elections in Zimbabwe has
      been documented before. A fact-finding mission was planned and undertaken two
      months ahead of the presidential election March 2002. METHODOLOGY: We interviewed
      and examined persons who alleged exposure to politically motivated torture, ill
      treatment and other human rights abuses. We assessed the validity of individual
      statements of torture and ill treatment and assessed existing similarities
      between histories of individual interviewees, e.g., as to timing of the assault
      and use of torture instruments to further appraise the validity. We analysed the
      results of our findings in relation to a newly introduced law restricting civil
      rights, and to the experiences of disrespect for the rule of law in Zimbabwe.
      RESULTS: Four men gave accounts of being beaten systematically with barbed wire
      and electrical cable all over their bodies. The clinical findings were in
      complete agreement herewith and their histories were mutually consistent. In ten
      additional interviews, we collected evidence of killing, ill treatment and
      harassment including robbing of ID cards from torture victims. Apart from losing
      their vote in the forthcoming election, according to the new law, victims with
      stolen ID cards will be liable to up to six months imprisonment. According to
      precedents, perpetrators of election violence and torture can expect impunity.
      The rule of law and the new law undermines democratic rights and free and fair
      elections and facilitates election violence including torture. We received
      statements about interference by the police in the delivery of health care
      services in hospitals and the new law could impede health professionals in
      documenting and reporting crimes including torture. CONCLUSION: The rule of law,
      the law points to the deepest disrespect for democratic and human rights in
      Zimbabwe. Our findings fit into this pattern. Any election under these conditions
      cannot be free and fair. Health professionals are hindered in exercising their
      duties both in terms of offering services and in terms of documentation and
      surveillance of human rights abuses. The international community should monitor
      the situation in Zimbabwe and strengthen the sanctions if torture systematically
      is used against opponents of the government or if the food aid is provided
      selectively to supporters of the government.

PMID- 12238287
TI  - The quality of routine oral anticoagulant therapy in a large geographical area. A
      survey of 310,300 inhabitants.
AB  - INTRODUCTION: To identify all patients undergoing routine oral anticoagulant
      therapy (OAT) in a large geographic area as well as the quality of OAT.
      METHODOLOGY: In the admission area of Aarhus County Hospital, Denmark (310,300
      inhabitants), we conducted a population-based prospective observational study 1
      April 1997 to 31 March 1998, using the Laboratory Information System to identify
      all patients and their related International Normalized Ratio (INR)-values as
      well as their monitoring physician. Main outcome measures were, incidence rate,
      point prevalence and the quality of OAT based on measurement of the time (in
      days) of INR-values within therapeutic interval (TI) of OAT. RESULTS: 1609
      patients (median age: 68.0 years; range 0.2-95.0) corresponding to 1155 patient
      years on OAT were identified. 585 patients were started on OAT within the time
      period, corresponding to an incidence rate of 188 patients/year/100,000
      inhabitants. September 1st 1997, 1174 patients were on OAT, equal to a point
      prevalence of 378 patients/year/100,000 inhabitants. Overall, 71% of treatment
      time (in days) INR was within the TI. Among patients monitored by an outpatient
      clinic or by a general practitioner, the time of INR within TI were 76.5% and
      69.9%, respectively (p < 0.0001). CONCLUSION: The result indicates that the
      quality of routine OAT in this geographical area is in accordance with other
      similar studies. The quality might be better in the outpatient clinics although
      the result could be due to selection bias. The method to identify OAT patients is
      convenient and precise, making continuous surveillance of rate of incidence,
      point prevalence as well as quality of OAT in large geographic areas, possible.

PMID- 12238288
TI  - Summary measures of population health. An overview.
AB  - The objective of the paper is to give a conceptual overview of old and new
      measures of a nation's state of health with special focus on new measures seeking
      to combine mortality with morbidity, functional and quality of life dimensions.
      Internationally, the development has given rise to two different movements. One
      (in Denmark and the EU) aims to develop a large number of standardised
      indicators, while the other (the WHO and the World Bank) builds on the idea that
      it must be possible to combine the many indicators into a single summary measure
      of a nation's state of health. In the summary measures, distinction is made
      between health expectancies and health gap measures. Attention is given to
      reviewing DALY (disability-adjusted life years), disability weights, and the
      social value choices applied in WHO's World Health Report 2000.

PMID- 12238289
TI  - The prevalence of latex sensitisation and allergy in Danish atopic children.
      Evaluation of diagnostic methods.
AB  - BACKGROUND: All over the world natural rubber allergy is reported to be
      responsible for a wide spectrum of allergic symptoms ranging from mild rhinitis
      to severe anaphylaxis. AIM: To estimate the prevalence and the clinical
      significance of latex sensitisation in atopic children seen in a university
      paediatric outpatient clinic. MATERIALS AND METHODS: During 1997-1998, a total of
      one hundred atopic children (4-14 years old, 64 boys and 36 girls) were
      consecutively screened for latex sensitisation by skin prick tests (SPTs) with
      standard inhalant allergens (ALK) and latex (Stallergenes SA), measurement of
      specific IgE (CAP System, Pharmacia, and Magic Lite, ALK) and total IgE. A
      clinical history with attention to surgical history, latex exposure and presence
      of symptoms possibly due to latex or food allergy was obtained. RESULTS: Five
      children (5%) had positive SPT to latex. Four (4%) had positive specific IgE to
      latex but had a negative SPT to latex. Only one patient (1%), who had spina
      bifida, had a positive SPT together with symptoms which could be related to latex
      allergy. This patient also had RAST class 4 to latex both with CAP System and
      Magic Lite. A history of previous surgery was found in only one of the children
      with positive latex SPT. Latex CAP System was positive in two of the five latex
      SPT positive patients, and latex Magic Lite in one of the five. In one patient
      without any symptoms of latex allergy, both SPT and in vitro tests were positive.
      Another child without symptoms, and with negative SPT, also had positive in vitro
      results. CONCLUSION: We found that the prevalence of sensitisation to latex was
      9% in atopic children, but the prevalence of manifest type 1 latex allergy was
      only 1%. Latex allergy in atopic children seems to be a small problem in Denmark.
      How to evaluate the significance of positive in vitro tests and positive latex
      SPT in patients without symptoms to latex, remains an open question.

PMID- 12238290
TI  - Mortality and causes of death in patients with "lupoid hepatitis." A long-term
      follow-up study in Denmark.
AB  - BACKGROUND: The mortality and causes of death in patients with "lupoid
      hepatitis", corresponding to the recent term autoimmune hepatitis, have rarely
      been reported. METHODS: We identified all patients discharged from hospital with
      a diagnosis of "lupoid hepatitis" from 1 January 1977 until 31 December 1993 in
      the Danish National Registry of Patients. The causes of death for the cohort were
      determined by linkage of the personal identification number with the Danish Death
      Registry. The cohort was followed until 31 December 1996. The expected number of
      deaths was estimated from the national age, sex, calendar period and cause
      specific death rates; and the standardised mortality ratio was calculated.
      RESULTS: We identified a total of 96 patients. The mean age was 50 years, and 71%
      of the patients were female. The mean follow-up period was 7.5 years, and after
      12 years of follow-up, 50% of the patients were still alive. The overall
      standardised mortality ratio was 3.7 (95% CI, 2.7-5.0). The risk of dying from
      liver cirrhosis was increased 51.2-fold (95% CI, 22.1-100.9) compared with the
      general population. CONCLUSIONS: Patients with "lupoid hepatitis" have a reduced
      life expectancy, mainly caused by excess deaths from liver cirrhosis, malignancy
      and heart disease.

PMID- 12238291
TI  - Using the right questionnaire is a crucial step in understanding the connections
      between physical activity and health.

PMID- 12238292
TI  - The making of an epidemiological theory of bias and confounding.

PMID- 12238293
TI  - Sol Levine and Jonathan Mann: two pioneers of public health remembered.

PMID- 12238294
TI  - The privilege of consciousness: an interview with Sol Levine. Interview by Anne
      Brunner. 12 April 1995.

PMID- 12238295
TI  - Commentary. I. Sol Levine's legacy.

PMID- 12238296
TI  - Commentary. II. Humanity in public health.

PMID- 12238297
TI  - History of bias.
AB  - Epidemiologists have always been conscious of the importance of controlling for
      distortions, although the definition itself of bias has changed over time.
      Central to this discussions in the past was the relative vulnerability of
      different study designs to bias and uncontrollable confounding (confounding being
      clearly distinguishable from bias, as a problem of inter-mixed causal effects due
      to the non-random distribution of risk factors within the study population). In
      particular, controversy arose over aspects of case-control study design. Also a
      formulation of "typologies of bias" during the 1970s helped to define some of the
      most important sources of distortion in the design, analysis and interpretation
      of epidemiological studies. The subsequent period--until now--has been
      characterised by more formal and systematic definitions.

PMID- 12238298
TI  - Lifestyle patterns concerning sports and physical activity, and perceptions of
      health.
AB  - OBJECTIVES: To explore the perceptions of health and physical activity, and the
      associations between these two areas from a theoretical lifestyle perspective.
      METHODS: Data was collected by means of a self-administered questionnaire, among
      3019 adults attending centres for preventive medicine in France. Correspondence
      analysis examined the significance of the relationships between perceptions of
      health and perceptions of sports and physical activity. RESULTS: Four principal
      types of subjects emerged from the factor analyses expressing four different
      lifestyle patterns. "Non physically active lifestyle: a feeling of not being
      healthy", "Physically active lifestyle, pleasure/leisure-oriented", "Necessarily
      physically active lifestyle, regardless of health", "Physically active lifestyle
      aimed at stress relief". CONCLUSIONS: The sociological approach helps tackle
      sports and physical activity as behaviour patterns but also and especially as a
      health orientation connected with the socio-economical climate. This approach
      also gives sports practice back its meaningful cultural dimension.

PMID- 12238299
TI  - Rethinking and rescoring the SF-12.
AB  - OBJECTIVES: To derive and assess the validity of an Australian version of the SF
      12 quality-of-life questionnaire. METHODS: Using regression methods and
      structural equation modelling to obtain item weights, an Australian version of
      the SF-12 was derived from Australian population survey data and compared to the
      existing United States (US) SF-12 variable set. RESULTS: The Australian version
      of the SF-12 explained 94% of the variation for physical components summary (PCS)
      and the mental components summary (MCS) of the SF-36 questionnaire. There was
      high level of agreement on the MCS and PCS summary scores between both versions
      of the SF-12 and the SF-36. CONCLUSIONS: Although it is possible to derive a
      valid Australian version of the SF-12 it is concluded the US version of the SF-12
      be used for reasons of international comparability, but using item weights
      derived from structural equation modelling.

PMID- 12238300
TI  - The development of a questionnaire to assess past year physical activity in a
      multi-ethnic/racial urban population.
AB  - OBJECTIVES: Describe the development of a questionnaire to assess past year
      physical activity, including activities of daily living, in a multi-ethnic/racial
      cohort. Describe energy expenditure (EE) patterns in the sample used for
      questionnaire development. METHODS: 24-hour activity recalls were collected from
      a convenience sample (N = 367) at four New York City health agencies (October
      1999-February 2000). EE was determined at the population, subgroup, and
      individual level. EE distributions were compared. RESULTS: Activities identified
      were similar to those on established questionnaires. Subgroup and individual EE
      differences were noted. Median EE at the Chinese and Puerto Rican sites were
      lower than those at the Caribbean or Dominican sites. No clear age pattern was
      apparent. Overall, a greater percentage of daily EE was spent in low intensity
      activities. The resultant 30-minute interviewer-administered questionnaire
      ascertains patterns (frequency and duration) of domain-specific (recreational,
      household, occupational, and transportation) activity. This information combined
      with published intensity levels provides summary EE measures. CONCLUSION:
      Variation in EE levels requires information on activity type and amount. Summary
      activity measures can be used to rank individuals analogous to nutrient food
      frequency measures.

PMID- 12238301
TI  - Medical ethics after the September 11th terrorist attacks.

PMID- 12238302
TI  - [Vaccination is not only a pediatric measure].

PMID- 12238303
TI  - New aspects in prophylaxis of ophthalmia neonatorum (Crede prophylaxis).

PMID- 12238304
TI  - Mast cell leukemia--a rare form of myeloid leukemia.

PMID- 12238305
TI  - New vaccination strategies for low- and non-responders to hepatitis B vaccine.
AB  - The currently available recombinant hepatitis B vaccines are safe, efficacious
      and immunogenic. Nevertheless, a high rate of low- and nonresponsiveness to the
      current vaccine poses a problem since this group remains susceptible to infection
      with hepatitis B virus. Efforts are underway to develop new vaccines and
      strategies to enhance seroprotection rates. One possibility under investigation
      is the low-dose intradermal administration of vaccine since the immune system is
      well represented in both the epidermis and the dermis. Despite encouraging
      results concerning the immunogenicity in previous non-responders, the main
      difficulty is the technique of administration and unacceptable local adverse
      effects. Promising data have emerged from clinical trials evaluating the
      immunogenicity of new recombinant vaccines containing the complete pre-S1 and pre
      S2 regions of HbsAg and, more recently, of novel adjuvanted hepatitis B vaccines.
      Future approaches include DNA vaccination and expression of HbsAg determinants in
      live recombinant vectors.

PMID- 12238306
TI  - [Transcranial magnetic stimulation (TMS)--from diagnostic procedure to therapy].
AB  - Transcranial magnetic stimulation (TMS) has been a well-established diagnostic
      tool in neurological practice for many years. It has been shown to be a safe and
      well tolerated method. Lately this technique has also found its way to psychiatry
      for the treatment of mood disorders. Several studies which investigated TMS of
      deeper brain regions found antidepressive effects in analogy to electro
      convulsive therapy (ECT). This could present a significant advantage, because TMS
      provides non-invasive and painless stimulation of the cerebral cortex. The method
      is based on the principle that a time-varying magnetic field induces an electric
      field which leads to activation of inhibitory and excitatory neurons in neural
      tissue. The magnetic field pervades the intact scalp and skull without loss of
      energy. Both case reports as well as clinical studies have shown that TMS could
      present a promising option in the treatment of depression. A review of the
      literature demonstrates that further studies are needed to clarify many questions
      regarding technical and clinical aspects, such as dosage, duration of
      application, localization of the coils, as well as the impact of rapid-rate TMS
      and stronger magnetic field generators, before TMS will become an established
      tool in the treatment of psychiatric disorders.

PMID- 12238307
TI  - [Vaccine protection in the elderly: are Austrian seniors adequately protected by
      vaccinations?].
AB  - OBJECTIVE: The aim of the study was to evaluate, if elderly persons are
      sufficiently protected against infectious diseases by vaccination. PROBANDS AND
      METHODS: 300 elderly (> 60 years) and 300 young (< 35 years) persons from five
      Austrian cities were recruited according to the criteria of a field study.
      Antibody concentrations against tetanus, diphtheria, tickborne encephalitis and
      influenza were assessed by ELISA or by haemagglutination inhibition test. Disease
      and vaccination histories were recorded. RESULTS: The results of the study
      demonstrate that protection against infectious diseases was frequently
      insufficient in the elderly. This was partly due to the fact that old persons
      were not vaccinated according to recommended strategies. However, low antibody
      concentration and a short duration of protective humoral immunity were also
      observed in many elderly persons in spite of regular vaccination. This was not
      only the case in frail, but also in healthy elderlies. CONCLUSION: The data
      demonstrate that vaccination has a relatively weak and short-lasting effect in
      old age. The results of the study should stimulate discussions about strategies
      how vaccinations can be made more effective in old age. Improved campaigns,
      shortened vaccination intervals as well as the design of novel vaccines tailored
      to fulfill the specific demands of the aging immune system are imaginable.

PMID- 12238309
TI  - Social and economic outcome after posterior microforaminotomy for cervical
      spondylotic radiculopathy.
AB  - Between 1993 and 1998, the surgical technique of posterior cervical foraminotomy
      as described by Frykholm, with individual cervical nerve root decompression had
      been applied at the Neurosurgical Department of the University of Vienna. We
      conducted a retrospective study to assess the functional and socio-economic
      outcome. Thirty-two patients were included in this study, 21 men and 11 women
      with a median age of 48 years (range 30 to 70 years). Prior to surgical
      management, median duration of symptoms had been 7 weeks (range 1-50 weeks), with
      cervicobrachialgia in 28 of the patients, 27 of the patients had sustained
      radicular sensory loss, and in 25 of the patients radicular paresis occurred.
      Measured by the Prolo Functional Economic Outcome Rating Scale, 64% of the
      patients were classified with a good outcome (scale 8-10), 18% of the patients
      were classified with a moderate outcome (scale 5-7), and 18% of the patients were
      classified with a poor outcome (scale < 5). Two of the patients required
      additional anterior cervical discectomy and one patient suffered a superficial
      wound infection which needed surgical drainage. This study confirms that
      posterior microforaminotomy is a useful technique for degenerative disease
      causing cervical radiculopathy with the advantage of avoiding fusion and
      immobilisation. Criteria for evaluating the results of treating cervical spinal
      disorders vary widely. Comparative analyses of outcome among different therapy
      protocols are compromised by the diversity among the groups studied, as well as
      by the varying methods of measuring success. We propose a scale based on the
      socio-economic and functional status of the patient before and after treatment
      This scale is easily applicable and can delineate pre- and postoperative
      conditions of patients. A more universal acceptance of common criteria for
      judging the outcome of spinal operations should facilitate comparisons among
      various methods of treatment.

PMID- 12238308
TI  - Prophylaxis of ophthalmia neonatorum--a nationwide survey of the current practice
      in Austria.
AB  - The aim of this study was to analyze the current practice of Ophthalmia
      neonatorum prophylaxis in Austria. Questionnaires were sent to 107 hospitals with
      obstetric units, as well as to 490 registered community midwives, together
      looking after a yearly total of approximately 70,000 births. The overall return
      of the hospitals and midwives was 91.6% and 7.6%, respectively. RESULTS:
      Ophthalmia neonatorum prophylaxis is being applied by 93.8% of all respondents
      (hospitals 96.9%, and community midwives 82.3%). The three most frequently
      applied substances were Erythromycin (41.8%), Gentamicin (21.3%) and Silver
      nitrate (19.7%). Other substances were Tetracycline, Povidone-Iodine, Neomycin
      and Chloramphenicol. The reported overall-observation of chemical conjunctivitis
      after application of a prophylactic agent was 42.3% (55/133), typically after the
      use of Silver nitrate, Erythromycin or Tetracycline. The agent was determined by
      pediatricians (29%), in accordance to governmental decree (15%), by hospital
      policy (12%), effectiveness against Chlamydia and Gonococci (9%), by pharmacists
      (3%) and ophthalmologists (3%). 18% did not give any reason for the choice of
      agent. CONCLUSION: The rationale for prophylaxis and the substances used in
      Austria show heterogeneity. Seven prophylactic agents are used, two antiseptics
      and five antibiotics. 25% of the routine applicants are using substances
      (Gentamicin, Neomycin or Chloramphenicol) for which no evidence based efficacy
      for prophylaxis of Ophthalmia neonatorum has been demonstrated through clinical
      trials. However, 83.5% of the maternity units do not want changes in their
      current routine, unless there is a nation-wide agreement for Ophthalmia
      neonatorum prophylaxis.

PMID- 12238310
TI  - Procalcitonin in patients with acute myocardial infarction.
AB  - Acute myocardial infarction induces an inflammatory reaction. We related
      conventional inflammatory parameters including C-reactive protein, erythrocyte
      sedimentation rate, white blood cell count and axillary temperature to plasma
      concentrations of procalcitonin in patients with acute myocardial infarction. In
      a prospective-descriptive study, we evaluated 54 patients with acute myocardial
      infarction. During a time period of 8 days following myocardial infarction, C
      reactive protein, erythrocyte sedimentation rate, white blood cell count and
      axillary temperature as well as the plasma concentrations of procalcitonin were
      measured. Maximal procalcitonin remained normal (below 0.5 microgram/L) in
      patients with uncomplicated acute myocardial infarction. This contrasted with
      results obtained from patients additionally afflicted by pulmonary edema and
      cardiogenic shock, in whom maximal procalcitonin increased up to 5.24
      micrograms/L. Resuscitation after cardiac arrest and/or concomitant bacterial
      infection increased procalcitonin to a maximal value of 134 micrograms/L, which
      was independent of the severity of left heart failure. Conventional inflammatory
      parameters were all significantly increased even in the absence of cardiac and
      non-cardiac complications of acute myocardial infarction. In conclusion,
      procalcitonin increases in patients with acute myocardial infarction only if
      associated with severe left heart failure, resuscitation after cardiac arrest or
      in the presence of bacterial infections. Thus, procalcitonin may help to
      elucidate the etiology of systemic inflammatory response during the early course
      of acute myocardial infarction.

PMID- 12238311
TI  - Uric acid--a marker for systemic inflammatory response in patients with
      congestive heart failure?
AB  - Congestive heart failure is associated with hyperuricemia and elevations in the
      levels of circulating markers for inflammation. The purpose of this study was to
      assess the relationship between levels of serum uric acid, activity of the renin
      angiotensin-aldosterone system and TNF-alpha in heart failure patients with
      respect to the extent of left ventricular dysfunction. Circulating uric acid, TNF
      alpha, plasma renin activity and concentrations of aldosterone were measured in
      30 patients with congestive heart failure, divided into subgroups according to
      their NYHA class (II-IV). We found a significant step-by-step increase in TNF
      alpha among the subgroups. Significant differences among the subgroups were found
      for the values of uric acid and the values of plasma renin and aldosterone. Serum
      uric acid correlated significantly with TNF-alpha concentrations (r = 0.36, P <
      0.05) leukocytes (r = 0.38, P = 0.03) and ejection fraction (r = 0.64, P < 0.01).
      No significant correlation was found between the activity of the renin
      angiotensin-aldosterone system and uricemia (r = 0.34). In a multivariate model,
      uric acid concentration was predicted significantly by the ejection fraction and
      blood leukocytes, this relationship being independent of serum creatinine,
      treatment modality, age and gender. We conclude that serum uric acid may reflect
      the severity of systolic dysfunction and the activation of an inflammatory
      reaction in patients with congestive heart failure.

PMID- 12238312
TI  - Detection of graphite using laser microprobe mass analysis of a transbronchial
      biopsy from a foundry worker with mixed dust pneumoconiosis.
AB  - Inhalation of dust containing graphite can cause lung disease in foundry workers
      and workers in graphite mines or mills. Mixed dust pneumoconiosis caused by long
      term occupational exposure to graphite dust is a rare disease. Only a few cases
      of graphite pneumoconiosis have been reported in literature, and these were
      usually diagnosed post mortem. Our report is of an 80-year-old male patient who
      had worked in an iron foundry for 20 years and whose work had entailed regular
      contact with ground graphite and foundry vapors. Chest x-rays revealed both a
      reticular and nodular pattern in the lung, moderate apical distractions and
      pleural scarring, all of which were confirmed by high-resolution computed
      tomography. Bronchoalveolar lavage and transbronchial biopsies were also
      consistent with mixed dust pneumoconiosis, and due to the long-term dust
      exposure, graphite pneumoconiosis was strongly suspected. To confirm this
      diagnosis, the chemical composition of the dark granules in the semi-thin
      histological sections of the transbronchial biopsies were analyzed using laser
      microprobe mass spectroscopy. The mass spectra of these black particles were
      consistent with those of natural graphite powder. Comparative analyses of normal
      lung tissue did not produce similar spectral patterns. We conclude that histology
      and cytology does not always suffice to confirm a diagnosis of graphite
      pneumoconiosis, because black particles are also found in conditions resulting
      from other exposures, such as heavy smoking or coal mining. Analysis of the
      composition of particles deposited in the lung tissue offers more precise
      information, which can be used as evidence in occupational and forensic medicine.
      Laser microprobe mass spectroscopy can assess the mineral dust load in lung
      samples.

PMID- 12238313
TI  - [Aleukemic mast cell leukemia (formerly: "malignant mastocytosis"): an extremely
      rare form of leukemia. A case report and simultaneously a contribution to revised
      classification of mastocytosis].
AB  - The term mastocytosis denotes a heterogeneous group of rare hematological
      disorders characterized by abnormal accumulation of mast cells. While cutaneous
      mastocytosis is relatively frequent mast cell leukemia belongs to the rarest
      forms of human leukemia. In the following we present the case of an aleukemic
      mast cell leukemia and shall discuss the revised classification of mastocytosis
      based on the "Year 2000 Working Conference on Mastocytosis" held in Vienna,
      Austria. A 48 year-old caucasian man presented with a four-week history of
      diarrhea, obstipation, vomiting, rash, and mild fever. Clinical inspection
      revealed a disseminated itching rash and a mild hepatomegaly. Red and white blood
      cell counts were within the normal range. Levels of the alkaline phosphatase and
      serum histamine were significantly increased. There was no splenomegaly or
      lymphadenopathy. Cytologic and histologic investigation of the bone marrow
      revealed a marked increase in atypical mast cells. Since only a few circulating
      mast cells could be detected in a cytospin preparation of the blood, the
      diagnosis of an aleukemic mast cell leukemia was established. About four weeks
      after the diagnosis had been established, the patient died with signs of a
      hemorrhagic shock due to a massive gastrointestinal bleeding. Autopsy revealed
      widespread mast cell infiltration of bone marrow, spleen, liver and lungs, but
      also a small, deeply penetrating, non-specific duodenal ulcer. In conclusion,
      despite of presentation with signs of a primary gastrointestinal disorder, the
      patient was found to suffer from an exceedingly rare aleukemic mast cell leukemia
      ("malignant mastocytosis") and died after a total duration of the disease of only
      about three months.

PMID- 12238314
TI  - Heterotopic pregnancy: report of three cases.
AB  - OBJECTIVE: Heterotopic pregnancy, defined as concomitant intrauterine and ectopic
      pregnancy, is a rare event. Assisted reproductive technologies have led to an
      increase in the number of heterotopic pregnancies. MATERIALS AND METHOD: From
      1997 to 1999 three cases of heterotopic pregnancies were referred to the
      gynecological unit of the hospital of St. Polten. The condition was diagnosed at
      7, 8 and 12 weeks of gestation, respectively. Two patients had undergone assisted
      reproductive technologies and former pelvic surgery for tubal pregnancy. Two
      patients had intrauterine singleton pregnancies and one patient had an
      intrauterine twin pregnancy. In all cases the ectopic site presented as a
      ruptured tubal pregnancy and the treatment consisted of laparoscopic
      salpingectomy. RESULTS: In all patients the postoperative course was uneventful
      and the intrauterine pregnancy progressed. In one case recurrent preterm labor
      led to vaginal delivery at 33 weeks of pregnancy. In the case of twin pregnancy,
      a planned cesarean section was performed at 37 weeks of gestation. One patient
      delivered at term. All newborns were healthy. CONCLUSION: Knowledge of
      heterotopic pregnancy and understanding the epidemiological risk factors
      underlying this condition are important for early diagnosis with the aim of
      improving therapy and clinical outcome.

PMID- 12238315
TI  - [Guideline of the Austrian Society of Gynecology and Obstetrics on suspected
      sexual offenses. November 2001 status].

PMID- 12238316
TI  - The impact factor of Wiener klinische Wochenschrift.

PMID- 12238317
TI  - Nipah virus.

PMID- 12238319
TI  - DengueNet--WHO's Internet-based System for the global surveillance of dengue
      fever and dengue haemorrhagic fever (dengue/DHF) http://www.who.int/denguenet.
      Dengue/DHF--global public health burden.

PMID- 12238318
TI  - WHO awarded US$ 1.5 million to test new treatment for malaria.

PMID- 12238320
TI  - Lessons taught by Miss Evers' Boys: the inadequacy of benevolence and the need
      for legal protection of human subjects in medical research.

PMID- 12238321
TI  - Internet pharmacies: cyberspace versus the regulatory state.

PMID- 12238322
TI  - The strict Ohio Supreme Court decision in Biddle: third party law firm held
      liable for inducing disclosure of medical information.

PMID- 12238323
TI  - The stifling of competition by the antitrust laws: the irony of the health care
      industry.

PMID- 12238324
TI  - Denying medical staff privileges based on economic credentials.

PMID- 12238325
TI  - Washington v. Glucksberg: influence of the court in care of the terminally ill
      and physician assisted suicide.

PMID- 12238326
TI  - Cytogenetic changes in the liver of progeny of irradiated male rats.
AB  - The transgenerational transmission of radiation damage of rat genom was studied
      on the basis of cytogenetic changes in somatic cells (hepatocytes). It was found,
      that the irradiation of rat males with dose of 3 Gy of gamma radiation caused
      latent cytogenetic damage to the liver, which was expressed during the course of
      an induced proliferation of hepatocytes (by partial hepatectomy) by lower
      proliferative activity and a high frequency of chromosomal aberrations. In the
      progeny of irradiated males (in the F1 generation), the radiation damage to DNA
      was manifested by similar changes, i.e. by lower proliferation activity and
      increase in "spontaneous" chromosomal aberration occurrence in liver regeneration
      after partial hepatectomy. Irradiating the progeny of irradiated males (the total
      radiation load of the progeny being 3 Gy + 3 Gy) caused slighter changes in
      compared with irradiating the progeny of non-irradiated control males (the total
      radiation load of the progeny being 0 Gy + 3 Gy), which suggests some kind of
      adaptive response, which was also found in other experimental systems and
      parameters. An analogous course of RNA and DNA quantitative changes in the liver
      of the F0 and F1 generations of rats confirms the partial transmission of
      radiation damage of genom to the progeny.

PMID- 12238327
TI  - Establishment of an animal model for radiation-induced vomiting in rats using
      pica.
AB  - We investigated whether radiation-induced pica, a behavior characterized by the
      eating of a non-food substance, such as kaolin, can be used as an index of
      radiation-induced vomiting in rats. Since there was an individual difference in
      the susceptibility to pica, we selected rats that actually ate kaolin following X
      ray irradiation, and used them for the experiment. The total-body irradiation
      (TBI) increased kaolin consumption in a dose-dependent manner (sham, 0.05 +/-
      0.03 (SEM) g; 2 Gy, 0.38 +/- 0.11 g; 4 Gy, 1.54 +/- 0.28 g; 8 Gy, 3.55 +/- 0.67
      g), and the increased kaolin consumption after 4 Gy of TBI was inhibited by a
      pretreatment with the serotonin 5-HT3 receptor antagonist ondansetron (2 mg/kg,
      i.p.) (saline, 1.49 +/- 0.33 g; ondansetron, 0.75 +/- 0.11 g). Furthermore, 4 Gy
      of abdominal irradiation was more effective to induce pica than that of head
      irradiation (abdomen: 0.37 +/- 0.05 g, head: 0.06 +/- 0.01 g). These findings
      suggested that peripheral serotonergic pathway is predominantly involved in the
      development of radiation-induced pica in rats and that the radiation-induced pica
      could be useful as a behavioral index for the severity of radiation-induced
      vomiting in rats.

PMID- 12238328
TI  - Histological and elemental changes in the rat brain after local irradiation with
      carbon ion beams.
AB  - The left cerebral hemispheres of adult Sprague-Dawley rat brains were irradiated
      at doses of 30, 50, or 100 Gy with charged carbon particles (290 MeV/nucleon; 5
      mm spread-out Bragg peak). The spread-out Bragg peak used here successfully and
      satisfactorily retained its high-dose localization in the defined region. A
      histological examination showed that necrotic tissue damage, hemorrhage in the
      thalamus, and vasodilatations around the necrotic region were induced at 8 weeks
      after 100 Gy irradiation. The regions with tissue damage correlated well with
      those expected from the radiation-dose distribution, indicating an advantage of
      charged carbon particles for irradiating restricted brain regions. An X-ray
      fluorescent analysis demonstrated a decrease in the concentrations of K and P,
      and an increase in the concentrations of Cl, Fe, Zn in the damaged region at 8
      weeks post-irradiation, though no significant changes were observed before 4
      weeks of post-irradiation. This may indicate that even the very high radiation
      doses used here did not induce acute and immediate neuronal cell death, in
      contrast with ischemic brain injury where acute neuronal cell death occurred and
      the elemental concentrations changed within a day after the induction of
      ischemia.

PMID- 12238329
TI  - Inhibition of gamma-radiation induced DNA damage in plasmid pBR322 by TMG, a
      water-soluble derivative of vitamin E.
AB  - Alpha-tocopherol monoglucoside (TMG), a water-soluble derivative of alpha
      tocopherol, has been examined for its ability to protect DNA against radiation
      induced strand breaks. Gamma radiation, up to a dose of 6 Gy (dose rate, 0.7
      Gy/minute), induced a dose-dependent increase in single strand breaks (SSBs) in
      plasmid pBR322 DNA. TMG inhibited the formation of gamma-radiation induced DNA
      single strand breaks (SSBs) in a concentration-dependent manner; 500 microM of
      TMG protected the single strand breaks completely. It also protected thymine
      glycol formation induced by gamma-radiation in a dose-dependent manner, based on
      an estimation of thymine glycol by HPLC.

PMID- 12238330
TI  - Effect of a hypoxic cell sensitizer doranidazole on the radiation-induced
      apoptosis of mouse L5178Y lymphoma cells.
AB  - We investigated the sensitizing effect of the 2-nitroimidazole analogue
      doranidazole, a new hypoxic radiosensitizer, on radiation-induced apoptosis in
      L5178Y cells. Apoptosis was assessed by checking DNA ladder formation, the
      presence of sub-G1 peaks in flow cytometry, and chromatin condensation. A
      radiosensitizing effect of doranidazole was also confirmed by a soft-agar colony
      assay of surviving cells. In the assay of DNA ladder formation, DNA fragmentation
      was observed following irradiation under an aerobic or hypoxic condition with or
      without doranidazole. The proportions of the cells at the sub-G1 peak in a flow
      cytometric measurement was not very different among the irradiations at 5 Gy
      under the aerobic condition, 15 Gy under hypoxia, and 10 Gy with 1 mM
      doranidazole under hypoxia. The fraction of cells with chromatin condensation was
      found to be significantly increased with doranidazole up to 3 mM when applied
      under hypoxic irradiation, but did not increase even at 10 mM. The sensitizer
      enhancement ratio was estimated to be about 1.7 with a concentration of 1 mM.
      This enhancement ratio was not different from that observed by assaying cell
      survivals. On the other hand, doranidazole showed no radiosensitizing effect
      under aerobic conditions with 1 mM. In conclusion, the radiation-induced
      apoptosis of L5178Y cells was enhanced by doranidazole under hypoxia.

PMID- 12238331
TI  - Establishment of immortal normal and ataxia telangiectasia fibroblast cell lines
      by introduction of the hTERT gene.
AB  - To establish immortal human cells, we introduced the human catalytic subunit of
      telomerase (hTERT) gene into skin fibroblast cells obtained from normal and
      ataxia telangiectasia (AT) individuals of Japanese origin. After hTERT
      introduction, these cells continue to grow beyond a population doubling number of
      200 while maintaining their original radiosensitivity. Inductions of p53,
      phosphorylation of Ser15 in p53, and induction of p21 by X-ray irradiation in
      immortal cells derived from normal individual were not affected by the hTERT
      introduction. Both normal and AT immortal cells exhibited an apparent inhibition
      of growth as original primary cells when they reached confluence. Karyotype
      analysis has revealed that they are in a diploid range. These results suggest
      that cells immortalized by hTERT introduction retain their original
      characteristics except for immortalization, and that they may be useful for
      analyzing various effects of radiation on human cells.

PMID- 12238332
TI  - Putative tumor-suppressor gene regions responsible for radiation lymphomagenesis
      in F1 mice with different p53 status.
AB  - Regions of allelic loss on chromosomes in many tumors of human and some
      experimental animals are generally considered to harbor tumor-suppressor genes
      involved in tumorigenesis. Allelotype analyses have greatly improved our
      understanding of the molecular mechanism of radiation lymphomagenesis.
      Previously, we and others found frequent loss of heterozygosity (LOH) on
      chromosomes 4, 11, 12, 16 and 19 in radiation-induced lymphomas from several F1
      hybrid mice. To examine possible contributions of individual tumor-suppressor
      genes to tumorigenesis in p53 heterozygous deficiency, we investigated the genome
      wide distribution and status of LOH in radiation-induced lymphomas from F1 mice
      with different p53 status. In this study, we found frequent LOH (more than 20%)
      on chromosomes 4 and 12 and on chromosomes 11, 12, 16 and 19 in radiation-induced
      lymphomas from (STS/A X MSM/Ms)F1 mice and (STS/A X MSM/Ms)F1-p53KO/+ mice,
      respectively. Low incidences of LOH (10-20%) were also observed on chromosomes 11
      in mice with wild-type p53, and chromosomes 1, 2, 9, 17 and X in p53 heterozygous
      deficient mice. The frequency of LOH on chromosomes 9 and 11 increased in the
      (STS/A X MSM/Ms)F1-p53KO/+ mice. Preferential losses of the STS-derived allele on
      chromosome 9 and wild-type p53 allele on chromosome 11 were also found in the p53
      heterozygous-deficient mice. Thus, the putative tumor-suppressor gene regions
      responsible for lymphomaganesis might considerably differ due to the p53 status.

PMID- 12238333
TI  - Generation of large homozygous chromosomal segments by mitotic recombination
      during lymphomagenesis in F1 hybrid mice.
AB  - The loss of heterozygosity (LOH) has been reported in numerous neoplasms in both
      human and animals, and has often been observed in chromosomal regions, which
      contain tumor-suppressor genes. We previously found frequent LOH on chromosomes
      4, 12 and 19 in radiation-induced lymphomas from (BALB/cHeA x STS/A)F1 hybrid
      mice by allelotype analysis at polymorphic microsatellite loci. In this study, to
      elucidate the nature of allelic losses, we refined the loss regions on
      chromosomes 4, 12 and 19 of the tumors from the F1 mice and then analyzed them
      cytogenetically. The results represent evidence of a wide range of allelic losses
      owing to mitotic recombination on chromosomes 4 and 19 in the tumors, possibly
      reflecting functional losses of putative tumor-suppressor genes. It is suggested
      that the generation of these large homozygous chromosomal segments probably
      containing the affected genes is one of the genetic alterations responsible for
      tumorigenesis.

PMID- 12238334
TI  - Characterization of spontaneous mutation in the delta soxR and SoxS overproducing
      strains of Escherichia coli.
AB  - To examine the role of the soxRS regulon in mutagenesis, we characterized the
      spontaneous mutations occurring in the endogenous tonB gene in the delta soxR
      strain and the SoxS overproducing strain of Escherichia coli. Neither the delta
      soxR strain nor the SoxS overproducing strain led to an enhancement or
      diminishment of the spontaneous mutation frequency. By DNA sequencing, we
      determined 50 spontaneous mutants from the delta soxR strains, and found that 36%
      were both base substitutions and IS insertions, 14% frameshifts and 10%
      deletions. Among the base substitutions, G:C-->T:A transversions and G:C-->A:T
      transitions predominated, followed by A:T-->T:A transversions. We determined 54
      spontaneous mutants from the SoxS overproducing strains, and found that 37% were
      IS insertions, 31% base substitutions, 17% frameshifts, 9% deletions and 6%
      duplications. Among the base substitutions, G:C-->T:A transversions dominated,
      followed by A:T-->T:A transversions and G:C-->A:T transitions. These results were
      similar to those from the soxRS+ strains. Thus, it is suggested that the soxRS
      regulated genes do not play a significant role in the defense against spontaneous
      mutagenesis.

PMID- 12238335
TI  - Whole-body X-irradiation induces acute and transient expression of heme oxygenase
      1 in rat liver.
AB  - Activation of the stress-inducible heme oxygenase-1 (HO-1) gene by X-irradiation
      was investigated in rat liver. When male Wistar MS strain rats (8 weeks) received
      whole-body irradiation of 17.0 Gy, 7 h later the activity of heme oxygenase in
      the liver was significantly enhanced (2.5 times). The level of HO-1 mRNA
      expression was increased by 2.3 and 4.0 times 2 and 4 h after radiation, and then
      declined at 7 and 10 h to the level of 2.0 and 1.6 times of the control. When the
      X-ray dose was varied from 4.0 to 21.7 Gy, the transcription of the gene was
      enhanced at all doses and the level of activation was dose-dependent. Finally,
      western blotting of irradiated liver demonstrated a significant increase in the
      level of HO-1 induced by X-rays, peaking at 4 h. Thus, X-rays were confirmed to
      be stressors that induce acute HO-1 expression transiently in the liver.

PMID- 12238336
TI  - Professional & policies.

PMID- 12238337
TI  - Role of CT scan in the diagnosis of brain infections.
AB  - BACKGROUND: Brain infections are quite common in low socioeconomic class due to
      poor nutrition and over populated living conditions. The outcome is usually grave
      unless promptly diagnosed and properly treated. This study was designed to
      evaluate the role of CT Scan in the early and correct diagnosis of brain
      infection. METHODS: CT Scan brain both pre and post I/V contrast was performed in
      patients presenting with high grade fever and headache/neurological symptoms as
      well as ear and sinus problems. RESULTS: 250 consecutive patients with the above
      mentioned complaints underwent CT Scan brain. 114 patents had positive scans.
      This comes to about 45.6%. The remaining 136 patients with normal scans included
      uncomplicated meningitis cases as well as patients with normal cerebro spinal
      fluid/CSF laboratory reports. CONCLUSION: The study showed that CT Scan is a
      useful investigation in the definitive/final diagnosis of brain infection.

PMID- 12238338
TI  - Attitude of women of NWFP towards antenatal care.
AB  - BACKGROUND: A safe motherhood initiative is a global effort to reduce maternal
      mortality and morbidity. This aims to ensure improvement in the quality and
      safety of lives of women through adoption of health and non-health strategies.
      Antenatal care is a branch of preventive medicine dealing with prevention and
      early detection of pregnancy disorders. It is the key to modern obstetrics.
      METHODS: It was a descriptive type of study to find out the attitude of the women
      towards utilization of antenatal care facility at a newly commissioned hospital,
      Hayatabad Medical Complex, Peshawar, Pakistan in the first year of its working.
      RESULTS: We recorded 980 patients. All of them were married. Monthly attendance
      showed increasing trend. In this study 72.44% of the women were of 25-35 year of
      age while 11.42% were teenager. Multiparity was recorded in 38.97% and 12.14% had
      more then nine pregnancies. Six hundred and fifty patients were living near the
      hospital. 2.24% patients visited more than six times and 63.26% had one visit
      only, with the rest visiting for 2-5 times. Thirty patients had medical
      disorders. Obstetrical diseases were detected in 194 patients. Pregnancy losses
      contributed to 146 women and 3 women had more then 6 losses. 254 women selected
      hospital delivery. Out of then 160 women were booked in the 3rd trimester.
      Caesarean section rate among those women was 16.4%. CONCLUSIONS: The conclusion
      drawn was that the women living near the hospital used the facility. Antenatal
      care should be provided to the women at the doorstep of their house. There is a
      system of lady health workers that should be expanded to cover all areas. Basic
      health units must be fully equipped and staffed. Communication system should be
      improved. There is a need to include health education in the curricula of primary
      education.

PMID- 12238339
TI  - Changes in fibrinogen level in liver cirrhosis.
AB  - BACKGROUND: Liver cirrhosis causes significant morbidity and mortality in our
      country, however early diagnosis prevents complications and carries good
      prognosis. Estimation of fibrinogen level may be helpful in preventing bleeding
      tendencies. METHODS: Plasma fibrinogen level of 82 confirmed liver cirrhosis in
      18-60 years age admitted patients of Khyber Teaching Hospital were determined and
      compared with normal controls, to establish it as a marker for diagnosis in
      cirrhosis liver and prognosis. Fibrinogen level was determined by Fibriprest-2.
      RESULTS: Significantly low levels in patients were recorded as compared to
      controls. 40% cases showed low fibrinogen level, while nearly 44% had normal
      levels. CONCLUSION: Fibrinogen level was low in early and terminal cirrhosis and
      high in advancing cirrhosis as compared to controls that showed normal levels.

PMID- 12238340
TI  - Isolated pleural fluid lactic dehydrogenase level: a cost effective way of
      characterizing pleural effusions.
AB  - BACKGROUND: Characterization of pleural effusion into an exudate or transudate is
      usually the first step in diagnostic evaluation. Light's criteria have been
      universally accepted as gold standard in this regard. We wanted to see the
      utility of isolated pleural fluid lactic dehydrogenase level (representing one of
      Light's classical criteria) in characterizing pleural effusion in our setting. We
      also wanted to compare the accuracy of commonly used conventional criteria with
      Light's criteria of isolated pleural fluid lactic dehydrogenase. METHODS:
      Patients who underwent diagnostic thoracentesis for one-year period were studied.
      Characterization of pleural effusions using biochemical criteria including
      pleural fluid protein, lactic dehydrogenase level (LDH), red blood cell (RBC)
      count and white blood cell (WBC) count were identified and compared with
      predetermined clinical criteria (gold standard). For each biochemical criteria
      sensitivity, specificity, positive predictive value and negative predictive value
      were calculated. RESULTS: Sixty-two patients underwent diagnostic thoracentesis.
      Sixteen were excluded, as they did not fulfill predetermined clinical criteria.
      Eight patients had transudative effusion vs. 38 exudates. LDH was found to be the
      most sensitive (97.2%) while WBC > 1000/mm3 was the most specific (100%) of all
      the criteria looked at. The overall accuracy was highest for Light's criteria of
      isolated LDH > 200 IU/litre (95.6%) followed by pleural fluid protein, WBC count
      and RBC count. CONCLUSION: We conclude that isolated pleural fluid LDH, as a
      representative of classical Light's criteria, is the most accurate criteria for
      characterizing pleural effusions. Due to its low accuracy isolated pleural fluid
      protein should not be ordered routinely. This approach may result into potential
      cost savings in our economically restraint society.

PMID- 12238341
TI  - Tuberculous lymphadenitis in Afghan refugees.
AB  - BACKGROUND: Tuberculosis is a disease of poor countries. The war-stricken Afghan
      refugees, owing to abject poverty, illiteracy, lack of social awareness and poor
      hygienic conditions, are highly susceptible to tuberculosis. This study was
      conducted to assess the frequency of peripheral lymph node tuberculosis in Afghan
      refugees. METHODS: One thousand lymph node biopsies from Afghan refugees were
      examined histopathologically. The diagnosis was undertaken on morphological
      grounds. Lymph nodes containing caseating epithelioid cell granulomas were
      identified as tuberculous. Age and sex of the patient and site of biopsy were
      also recorded. RESULTS: Sixty nine percent of the nodes revealed tuberculosis.
      Male:Female ratio was 1:1.2. Of all the cases 72% cases were 10-30 years of age.
      The most common site involved was neck that was involved in 79% of cases.
      CONCLUSIONS: Tuberculous lymphadenitis has an alarmingly high prevalence in
      Afghan refugees of NWFP.

PMID- 12238342
TI  - Effect of frequent blood donations on iron stores of non anaemic male blood
      donors.
AB  - BACKGROUND: A healthy blood donor loses about 225 mg of iron per donation. This
      loss is made up very quickly by mobilizing the iron stores in form of ferritin,
      followed by replenishing the iron stores if diet is adequate. The situation,
      however, is different for donors with high frequency of blood donations. Their
      iron stores are under a constant pressure. In the absence of iron replacement
      this can lead to emptying of iron stores. We undertook this study to evaluate the
      effect of frequent blood donations on iron stores of regular male blood donors in
      Karachi. METHODS: This study was carried out at Department of Physiology, BMSI,
      JPMC, Karachi. Our subjects were 8 groups each with 20 non-anaemic male donors,
      of 20-40 years age (total = 160). The first group was 'control group' that
      comprised of first time donors, while the rest 7 groups comprised of donors who
      had donated 1-7 times in the last two years, the latest being at least 3 months
      back. The iron stores were measured by determining serum ferritin levels.
      RESULTS: We found reduction in serum ferritin with increasing frequency of blood
      donations that became very significant in donors donating 4 or more times in the
      last two years. Finding of 40% and 50% iron deficient subjects in the groups
      donating 6 and 7 times in two years respectively was a surprise for us, as this
      much high frequency has not been reported from elsewhere. We have tried to
      justify this extraordinary high frequency with the studies reporting low iron
      status of Pakistanis and Karachi population. CONCLUSIONS: Iron deficiency is very
      common in regular blood donors of Karachi, there is an immediate need to educate
      the donors about iron supplementation and yearly ferritin checking of so called
      'super donors'.

PMID- 12238343
TI  - Malignant sacrococcygeal yolk sac (endodermal sinus) tumor.
AB  - We report a 2 1/2 years old female child who presented with Malignant
      Sacrococcygeal Yolk sac (Endodermal Sinus) tumor as presacral mass with
      ulceration of overlying skin. Her ultrasonography (USG)abdomen revealed a huge
      presecral mass with irregular margins extending in to the pelvis, pushing the
      rectum antero-laterally. CT scanning of abdomen confirmed USG finding with out
      enlargement of retroperitoneal lymph nodes and no involvement of the liver. Serum
      AFP was abnormally elevated. The tumor was excised along with Coccyx in-toto
      through posterior approach dividing the sacrum and 3-Drugs (VAC) Chemotherapy
      started postoperatively i.e. 2-weeks after surgery. Here we discuss our
      experience with this extremely rare malignant extra-gonadal germ-cell tumor and
      review of literature.

PMID- 12238344
TI  - Beta blockers: an important therapeutic modality for hypertensive diabetics.

PMID- 12238346
TI  - A comment on article by Khurshid et al (J Ayub Med Coll Abbottabad 2002;14(1):13
      15.

PMID- 12238347
TI  - Depression among parents of children with acute lymphoblastic leukemia.
AB  - BACKGROUND: The diagnosis of cancer in children can always be devastating to the
      patients as well as to their parents. Some degree of depression is to be expected
      among parents caring for a loved one with leukemia. This study was done to
      determine the frequency of depression in parents of children with acute
      lymphoblastic leukemia in relation to age, gender, education, occupation, and
      performance status of their patients. METHODS: The study was conducted at Shaukat
      Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan over a
      period of three months, from May, 2000 to July, 2000. Either parent of 60
      consecutive patients of acute lymphoblastic leukemia who achieved their first
      remission within last one-month were enrolled. Their age, gender, education,
      occupation, socioeconomic status, and non-medical risk factors of depression were
      recorded. The Mini Mental State Examination (MMSE) and Structured Clinical
      Interview according to the Diagnostic and Statistical Manual of Mental Disorders
      fourth version (SCID-IV) were used to identify parents with depression. Data
      regarding sociodemographic variables and non-medical risk factors of depression
      were recorded on data capture form. Data analysis was done by SPSS--10. Overall
      differences were assessed using percentages and chi-square. RESULTS: Depression
      was found to be positive among 56.7% (34) of the parents. It was more common
      among mothers, less educated parents and among those belonging to lower
      socioeconomic class. Parents attributed their depression to multiple factors;
      most common were related to concerns about family's well-being, financial
      constraints and distressing change in role and responsibilities. CONCLUSION: This
      study concludes that a majority of attending parents of children with acute
      lymphoblastic leukemia suffers from depression and it is not associated with any
      of the variables studied. We need to conduct further studies on a large number of
      parents in order to make any logical conclusions.

PMID- 12238348
TI  - [Mechanisms of generation of mismatch negativity and their role in discrimination
      of short acoustical stimuli].
AB  - The effect of stimulus duration on the mismatch negativity in the auditory event
      related potentials was used to study the role of mismatch negativity (MMN) in
      discrimination of short acoustical stimuli. We compared discrimination of
      different short acoustical stimuli in active variant of "odd ball" paradigm. It
      was shown that it is possible to discriminate between standard and deviant
      acoustical stimuli which do not produce MMN in passive condition. It makes
      possible to estimate behavioural significance of MMN in active discrimination
      task. If the MMN had not been recorded in passive condition, that leads to an
      increase of reaction time in active paradigm approximately by 50 ms.

PMID- 12238350
TI  - [Relationship between perennial biorhythms of the hemogram elements and dynamic
      of heliogeophysical factors in humans].

PMID- 12238349
TI  - [Participation of the GABA B receptors in presynaptic inhibition of the spinal
      cord descending projections fibers in the frog Rana ridibunda].
AB  - (-)-Baclophen was found to depress in a dose-dependent and reversible way the
      excitatory post-synaptic potentials (EPSPS) of motor neurons and the ventral root
      potentials evoked by stimulation of fibres of the ipsi- and contralateral ventral
      columns. The (-)-baclophen depressing effect could be eliminated with saclophen.
      Picrotoxin eliminated the depressing effect of the GABA on the descending EPSPS.
      Depressing effects of (-)-baclophen and GABA upon the ventral root potentials
      were also shown. The data obtained in pharmacological analysis corroborate to a
      certain extent existence of the GABAB receptor presynaptic inhibition in
      descending fibres monosynaptically corrected with the spinal cord motor neurons
      in the frog Rana ridibunda.

PMID- 12238351
TI  - [Interactions of peripheral mu-opioid receptors and K(ATP)-channels in regulation
      of cardiac electrical stability in ischemia, reperfusion, and postinfarction
      cardiosclerosis].
AB  - It has been shown that mu-opioid receptor stimulation by intravenous
      administration of the selective mu receptor agonist DALDA in a dose of 0.1 mg/kg
      prevented ischemic and reperfusion arrhythmias in rats subjected to coronary
      artery occlusion (10 min) and reperfusion (10 min), and also increased the
      ventricular fibrillation threshold in rats with postinfarction cardiac fibrosis.
      These effects were abolished by pre-treatment with the selective mu receptor
      antagonist CTAP in a dose of 0.5 mg/kg or by prior injection of the opioid
      receptor antagonist naloxone methiodide (2 mg/kg) which does not penetrate the
      blood-braib barrier. Both antagonists by themselves had no effect on the
      incidence of occlusion or reperfusion-induced arrhythmias or on the ventricular
      fibrillation threshold. Pre-treatment with ATP-sensitive K+ channel (KATP
      channel) blocker glibenclamide in a dose of 0.3 mg/kg completely abolished the
      antiarrhythmic effect of DALDA. We believe that DALDA prevents occurrence of
      electrical instability during ischemia and reperfusion and increases the
      ventricular fibrillation threshold in rats with postinfarction cardiac fibrosis
      via stimulation of peripheral mu-opioid receptor which appear to be coupled to
      the KATP channel.

PMID- 12238352
TI  - [Dependency of characteristics of heart rate variability on the average value of
      the R--R-intervals].
AB  - By the means of spectral analysis, dependency of heart rate variability (HRV) on
      average R--R-intervals (R--Rav, sec) is explored at controlled (forced)
      breathing. According to our findings, the dependency of the peak frequency at a
      spectral density graph for source series of R--R-intervals upon the RRav may be
      presented by the following formula: fp 1.0 = fr: RRav, where fp 1.0--peak
      frequency when R--Rav = 1.0 sec, fp--peak frequency at current R--Rav. For
      correcting (standardization) the frequency domain borders of spectral power (fd)
      of sources series of the R--Rav-intervals it is possible to use the formula: fd =
      fd 1.0 R--Rav, where fd 1.0--frequency domain border at R--Rav = 1.0 sec. The
      correction (standardization) of frequency domain borders of spectral power (fd),
      frequency peaks (fp 1.0) of sources series of the R--Rav-intervals as compared to
      current R--Rav allows to compare different series of the R--Rav-intervals without
      using the transformation to the discrete event series (DES).

PMID- 12238353
TI  - [The role of endogenous modulators of chemoreactivity in the regulation of
      coronary blood flow].
AB  - 32 circulatory bands of coronary arteries of 5 pigs were studied. It has been
      revealed that the bands develop long-term tonic contraction activity in Krebs's
      solution (30 mM of KCl). In this case adrenalin in concentration of 10(-7) g/ml
      causes mild relaxation. In concentration of 10(-6) g/ml, it causes obvious
      relaxation. Trimetazidin and mildronat do not affect tonic contraction of the
      bands. They can quickly and reversibly increase relaxation effects of adrenaline.
      The preparations can increase ten-fold beta-adrenoreactivity of smooth muscles.
      This shows an important role of endogenic sensibilizers of beta-adrenoreceptors
      in regulation of coronary blood flow in humans.

PMID- 12238354
TI  - [The effect of He-Ne laser radiation on myocardium mechanical activity in rats].
AB  - In isolated papillary muscles, a 5-minute irradiation with the He-Ne-laser
      Shuttle-1 enhances the maximal strength of isometric contraction and acceleration
      of relaxation. In physiological mode of mechanical loads, the irradiation with
      the laser red light enhances the myocardium contractability at all final systolic
      lengths with simultaneous enhancement of the isometric relaxation velocity at
      great systolic lengths and a deceleration of the relaxation at lesser lengths.
      Under the He-Ne-laser effect, restoration of rhythm-inotropic relationships
      occurred in the myocardium.

PMID- 12238355
TI  - [Cerebral blood flow modulates hyperbaric oxygen induced neurotoxicity by
      neuronal and endothelial nitric oxide].
AB  - The goal of work was to reveal changes in microcirculation of the rat brain and
      the role of nitric oxide (NO) in development of seizures at hyperbaric oxygen
      exposure. The Wistar rats with implanted paired platinum electrodes in left and
      right striatum were used for experiments. The latency of seizures was defined by
      the EEG, the cerebral blood flow (CBF) was measured by hydrogen clearance. One
      group of animals was exposed to a 5-ata oxygen, while the others before oxygen
      treatment were injected with: Nw-nitro-L-arginine methyl ester (L-NAME),
      blockator of constitutive NO synthase; 7-nitroindozol (7NI), specific inhibitor
      of neural NO synthase. The latency of seizures was 41 +/- 1.9 min at 5 ata oxygen
      exposure. CBF was decreased to 10-14% but before seizures it increased to 23 +/-
      9%. L-NAME and 7NI prevented development of hyperoxygen hyperemia and onset of
      seizures. The results indicate occurrence of hyperbaric oxygen changes of the CBF
      that modulate neurotoxic effects of NO in neurons as well as in cerebral vessels.

PMID- 12238356
TI  - [Lipid peroxidation in the rats striatum during stress after cortisol
      administration].
AB  - Lipid peroxidation in the rat striatum under stress after cortisole injection was
      investigated. Three days cortisole injections (25 mg/kg every day) do not affect
      the level of lipid peroxidation products 6 days after termination of the hormone
      injection. However, in these periods, cortisole injected rats had a more
      significant response of lipid peroxidation to stress than the control animals
      (decrease of intermediate products and increase of Shift bases). Thus, the
      hormone injection induced a long-term changes in so important a regulatory system
      of the organisms as the lipid peroxidation, causing sensitization of its response
      to stress.

PMID- 12238357
TI  - [The influence of pineal peptides on in vitro immunoglobulin secretion by Peyer's
      patches in rats].
AB  - The influence of the pineal peptides (1 mcg/ml) on immunoglobulin secretion by
      rat's Peyer's patches isolated from nonimmunized rats and from orally immunized
      by ovalbumin during 40 min incubation, was investigated. Using alpha- and beta
      adrenoblockers--phentolamine hydrochloride (0.02 mg/ml) and anaprilin (0.6
      mg/ml), respectively--the possibility of pineal peptides' effect on the gut
      secondary lymphoid organ' adrenoreceptors, was evaluated. Basic levels of
      immunized rats' control Peyer's patches secretory activity were 2.4--fold (p <
      0.01) higher than those of non-immunized rats. The effect of pineal peptides on
      antibody-producing cells' secretory activity depended on Peyer's patches'
      functional condition. Application of pineal peptides led to a 35% (p < 0.05)
      increasing of immunoglobulin secretion by non-immunized rat Peyer's patches and
      to a 25% (p < 0.05) decreasing of antibody production by immunized rats lymphoid
      organs. These data suggest that the pineal peptides activation influence on
      Peyer's patches antibody-producing cells of nonimmunized rats connected with
      alpha-adrenoreceptors, and inhibiting action of these peptides on immunized rats
      lymphoid organs immunoglobulin secretion are not mediated through
      adrenoreceptors.

PMID- 12238358
TI  - [Correlation between sex hormone receptors in normal and cancerous target
      tissues].
AB  - According to the classic model of regulation of sex hormone receptors
      biosynthesis in target tissues, oestrogen stimulates and progesterone inhibits
      biosynthesis in both receptors. One of the consequences of this model is a direct
      correlation between oestrogen (ER) and progesterone receptors (PR) in target
      tissues. Here we investigate a correlation between ER and PR in calf endometrium
      and breast cancer (BC) tissues of women. A direct correlation was found between
      receptors in the calf endometrium (r = +0.70; p < 0.01). There were three
      variants of BC tissues: without correlation, with positive correlation (r =
      +0.49; p < 0.01), and with non-linear negative correlation between ER and PR. The
      last variant of samples were detected exclusively in patients operated in spring
      and fall. The non-linear negative correlation between ER and PR in BC tissues in
      spring and fall may indicate disregulation of sex hormone receptors biosynthesis
      under the influence of external factors.

PMID- 12238359
TI  - [The anxiety level and synthesis of neurosteroids in the brain of prenatally
      stressed male rats].
AB  - Prenatal stresses significantly reduce the anxiety level and enhance motor
      activity in mature male rats. An enhancement of the 5 alpha-reductase activity
      occurs in the hypothalamus, hippocampus, and the brain frontal cortx. The data
      obtained suggest that behavioural changes in mature male rats due to prenatal
      stresses may be a consequence of an increased forming of active progesterone
      metabolities in the brain.

PMID- 12238360
TI  - [The influence of substance P central administration on ethanol intake in rats
      chronically exposed to alcohol].
AB  - The influence of central substance P (SP) administration on alcohol intake and
      brain dopamine metabolism within mesocortico-limbic and nigrostiatal systems of
      rats exposed to ethanol, was studied. During 6 months, the rats consumed 15%
      ethanol solution instead of water. Central administration of SP (3 mcg/kg)
      decreased alcohol consumption by 41% in alcohol-preference animals. After long
      term ethanol exposure ratios DOPAC/DA and HVA/DA were reduced in striatum and
      accumbens. SP in dose 3 mcg/kg increased content of DOPAC by 17% and HVA by 23%
      as well as DOPAC/DA by 9%, HVA/DA by 19% in accumbens. Whereas in striatum only
      increased DOPAC (28%) and HVA (29%) were observed as compared with saline-treated
      rats.

PMID- 12238361
TI  - [Comparative characteristic of respiratory pattern responses to kainic acid
      microinjections in different parts of the nucleus ambiguous].
AB  - In rats, local chemical isolation of neurones by the kainic acid helped to
      investigate into comparative role of different parts of the n. ambiguus in
      respiratory control mechanisms. We disclosed specific peculiarities of responses
      of rhythm and respiratory pattern to chemical isolation of different parts of the
      n. ambiguus. In particular, it was found that consecutive isolation of the left
      and right rostral parts of the n. ambiguus caused a significant decrease of the
      respiration rate and respiratory volume and also resulted in irreversible
      cessation of respiration in 83% of experiments. Isolation of symmetric medial
      parts of the n. ambiguus resulted in bradypnoe and a decrease of pulmonary
      ventilation; maximal respiratory effect was recorded after kainic acid injection
      in the symmetric part only, thus the irreversible cessation of respiration was
      recorded in 50% of experiments. After isolation of symmetric caudal parts of the
      n. ambiguus we observed an insignificant decrease of the respiration rate without
      significant changes of the respiratory volume, and number of the respiration
      cessation was minimal: 33%.

PMID- 12238362
TI  - [The differentiation of rhythmogenic characteristics of the ureter's different
      regions in guinea pigs].
AB  - Characteristics of rhythmogenic pacemakers of the ureter's perirenal middle and
      peribladder region morphologically and electrophysiologically are analysed in
      guinea pigs both in presence of spreading activity and breach of conductivity. It
      was shown that the action potential's amplitude of the middle region is the
      highest and duration of the spike activities from perirenal zone is maximal and
      all three regions are characterised by different functional conditions.

PMID- 12238363
TI  - [Analysis of correlations between the rate of oxygen consumption, body
      temperature, and the content of mitochondrial protein in the mouse liver].

PMID- 12238364
TI  - [Oxygen consumption and energy expenditure related to performance of the Genchi
      and Schtange tests].

PMID- 12238365
TI  - Epizootiology of Eustrongylides ignotus in Florida: distribution, density, and
      natural infections in intermediate hosts.
AB  - A total of 63,451 fish, representing 39 species, was collected from 176 foraging
      sites used by ciconiiform wading birds in peninsular Florida (USA) and examined
      for larvae of Eustrongylides ignotus. Infected fish were identified from 30 (17%)
      of the sites, all of which had been altered by human disturbance such as removal
      of sediment to construct ditches and dikes, improve water flow, or increase
      storage capacity and had a history of receiving anthropogenic nutrients such as
      sewage effluent, urban runoff, or agricultural runoff. The mosquitofish (Gambusia
      holbrooki) and several species of sunfish (Centrarchidae) were the most important
      intermediate hosts. Infected fish were not collected at any of the unaltered
      sites. A total of 10,508 oligochaetes (representing 36 species) was identified
      from 22 sites that had fish infected with E. ignotus and 36 sites where no
      infected fish were collected. None of the oligochaetes was infected with larvae
      of E. ignotus. Immature tubificids without hair setae (probably Limnodrilus sp.),
      Dero digitata, and L. hoffmeisteri were the most abundant oligochaetes at sites
      where infected fish occurred, making up 78% of the total collected. Compared to
      unaltered sites, altered sites were characterized by higher mean densities of
      fish and oligochaetes; surface waters with decreased dissolved oxygen and
      increased total nitrogen, total phosphorus, and chlorophyll-a; sediments with
      higher soil oxygen demand and total phosphorus; larger grain sizes; and higher
      percentage emergent vegetation and grasses.

PMID- 12238366
TI  - Serum antibody prevalence of malignant catarrhal fever viruses in seven wildlife
      species from Alaska.
AB  - Blood samples were collected from seven species of free-ranging ungulates in
      Alaska. Sera were tested for evidence of exposure to malignant catarrhal fever
      viruses (MCFV) by means of a competitive enzyme-linked immunosorbent assay.
      Antibody prevalences were as follows: muskox (Ovibos moschatus) 100 positive
      samples of 104 tested (96%); Dall sheep (Ovis dalli) 212 of 222 (95%); elk
      (Cervus elaphus) 14 of 51 (27%); bison (Bison bison) 34 of 197 (17%); caribou
      (Rangifer tarandus) nine of 232 (4%); Sitka black-tailed deer (Odocoileus
      hemionus sitkensis) one of 49 (2%); and moose (Alces alces) three of 219 (1%).
      Antibody prevalence in a bison population from the Interior was stable over a 5
      yr period. These results indicate that at least one virus in the MCF group is
      enzootic in Dall sheep and muskox in Alaska. Lower antibody prevalences in the
      other species in this survey suggest that MCFV are latent or subclinical in these
      free-ranging ruminants. Whole blood samples were collected from 14 Dall sheep and
      subjected to a polymerase chain reaction assay. Fragments of ovine herpesvirus-2
      DNA were detected in six of the samples. The significance of these findings for
      the health of free-ranging ungulates in Alaska is unknown.

PMID- 12238367
TI  - Evidence for infanticide in bottlenose dolphins of the western North Atlantic.
AB  - Nine bottlenose dolphin (Tursiops truncatus) calves that stranded in Virginia in
      1996 and 1997 died of severe blunt-force trauma. Injuries were concentrated on
      the head and chest and multiple rib fractures, lung lacerations, and soft tissue
      contusions were prominent. Skeletal and/or soft tissue trauma occurred
      bilaterally in all of the calves. One had a bite wound across the left mandible
      that exhibited deep punctures consistent with the tooth placement in an adult
      bottlenose dolphin. The lesions were not compatible with predation, boat strike,
      fisheries interactions, rough-surf injury, or blast injury. However, they were
      similar to traumatic injuries described in stranded bottlenose dolphin calves and
      harbor porpoises (Phocoena phocoena) in Great Britain attributed to violent
      dolphin interactions. The evidence suggests that violent dolphin behavior was the
      cause of the trauma in the nine calves reported here and that infanticide occurs
      in bottlenose dolphins of the western North Atlantic.

PMID- 12238368
TI  - Elemental and organochlorine residues in bald eagles from Adak Island, Alaska.
AB  - Adak Island is a remote island in the Aleutian Island archipelago of Alaska (USA)
      and home to various military activities since World War II. To assess the
      contaminant burden of one of Adak Island's top predators, livers and kidneys were
      collected from 26 bald eagle (Haliaeetus leucocephalus) carcasses between 1993
      and 1998 for elemental and organochlorine analyses. Mean cadmium, chromium,
      mercury, and selenium concentrations were consistent with levels observed in
      other avian studies and were below toxic thresholds. However, elevated
      concentrations of chromium and mercury in some individuals may warrant concern.
      Furthermore, although mean polychlorinated biphenyl and pp'
      dichlorodiphenyldichloroethylene concentrations were below acute toxic
      thresholds, they were surprisingly high given Adak Island's remote location.

PMID- 12238369
TI  - Medical dilemmas associated with rehabilitating confiscated houbara bustards
      (Chlamydotis undulata macqueenii) after avian pox and paramyxovirus type 1
      infection.
AB  - Projects to rehabilitate confiscated animals must carefully consider the risks of
      disease when determining whether to release these animals back into the wild or
      to incorporate them into captive breeding programs. Avipox and paramyxovirus type
      1 (PMV-1) infections are important causes of morbidity and mortality during
      rehabilitation of confiscated houbara bustards (Chlamydotis undulata macqueenii).
      This paper presents key findings of an intensive health monitoring program
      (physical condition, hematology, serology, endoscopy, microbiology, and virology)
      of two flocks of houbara bustards that survived outbreaks of septicemic avipox
      and PMV-1 respectively. Mortality in each flock from avipox and PMV-1 infections
      were 47% and 25% respectively, and the clinicopathologic features and management
      of each outbreak are presented. Avipox and PMV-1 viruses were not isolated from
      surviving birds monitored monthly for 11 mo after initial infection nor were
      septicemic or diptheritic avipox and PMV-1 infections detected in the captive
      breeding collection into which surviving birds were ultimately integrated up to
      24 mo later. Adenovirus was isolated from four birds during the study
      demonstrating that novel disease agents of uncertain pathogenicity may be carried
      latently and intermittently shed by confiscated birds. This paper demonstrates
      the risk of importing pathogens with illegally traded houbara bustards and
      reinforces the need for surveillance programs at rehabilitation centers for these
      birds. We recommend that confiscated houbara bustards integrated into captive
      breeding programs be managed separately from captive-bred stock. Other measures
      should include separate facilities for adult birds and rearing facilities for
      offspring derived from different stock lines and strict sanitary measures.
      Additionally, health monitoring of confiscated birds should continue after birds
      are integrated into captive flocks.

PMID- 12238370
TI  - Virologic investigations of free-living European bison (Bison bonasus) from the
      Bialowieza Primeval Forest, Poland.
AB  - We conducted virologic investigations on postmortem specimens from 261 free
      living European bison (Bison bonasus) from the Bialowieza Primeval Forest, Poland
      collected between 1990 and 2000. Fifty-four of 94 males had balanoposthitis; none
      of the 167 female bison examined had reproductive tract lesions. Peripheral
      blood, swabs, and various tissues were analyzed for bovine viruses as well as for
      viral DNA by bovine herpesvirus 1 (BoHV-1) and bovine herpesvirus 4 (BoHV-4)
      specific polymerase chain reaction (PCR) technique. An infectious bovine
      rhinotracheitis like BoHV-1 strain was isolated from the spleen of a female bison
      calf and additionally was detected by nested PCR from splenic tissue. None of the
      bison had significant antibody titers against BoHV-1, bovine herpesvirus 2, BoHV
      4, caprine herpesvirus 1, cervid herpesvirus 1, or bovine viral diarrhea (BVD)
      virus-1. However, low antibody titers in two animals indicate that this European
      bison population has been exposed to BVD virus or BVD-like viruses and BoHV-2.

PMID- 12238371
TI  - Aerobic salivary bacteria in wild and captive Komodo dragons.
AB  - During the months of November 1996, August 1997, and March 1998, saliva and
      plasma samples were collected for isolation of aerobic bacteria from 26 wild and
      13 captive Komodo dragons (Varanus komodoensis). Twenty-eight Gram-negative and
      29 Gram-positive species of bacteria were isolated from the saliva of the 39
      Komodo dragons. A greater number of wild than captive dragons were positive for
      both Gram-negative and Gram-positive bacteria. The average number of bacterial
      species within the saliva of wild dragons was 46% greater than for captive
      dragons. While Escherichia coli was the most common bacterium isolated from the
      saliva of wild dragons, this species was not present in captive dragons. The most
      common bacteria isolated from the saliva of captive dragons were Staphylococcus
      capitis and Staphylococcus capitis and Staphylococcus caseolyticus, neither of
      which were found in wild dragons. High mortality was seen among mice injected
      with saliva from wild dragons and the only bacterium isolated from the blood of
      dying mice was Pasteurella multocida. A competitive inhibition enzyme-linked
      immunosorbent assay revealed the presence of anti-Pasteurella antibody in the
      plasma of Komodo dragons. Four species of bacteria isolated from dragon saliva
      showed resistance to one or more of 16 antimicrobics tested. The wide variety of
      bacteria demonstrated in the saliva of the Komodo dragon in this study, at least
      one species of which was highly lethal in mice and 54 species of which are known
      pathogens, support the observation that wounds inflicted by this animal are often
      associated with sepsis and subsequent bacteremia in prey animals.

PMID- 12238372
TI  - Safety of Brucella abortus strain RB51 vaccine in non-target ungulates and
      coyotes.
AB  - Brucellosis is endemic in free-ranging elk (Cervus elaphus) and bison (Bison
      bison) in the Greater Yellowstone Area (GYA; USA). It is possible that an oral
      brucellosis vaccine could be developed and disseminated in the GYA to reduce
      disease transmission. Should this occur, non-target species other than elk and
      bison may come in contact with the vaccine resulting in morbidity or mortality.
      To assess biosafety, bighorn sheep (Ovis canadensis; n = 10), pronghorn
      (Antilocapra americana; n = 9), mule deer (Odocoileus hemionus; n = 11), moose
      (Alces alces shirasi; n = 10), and coyotes (Canis latrans; n = 24) were given a
      single oral dose of at least 1.0 x 10(10) colony-forming units of Brucella
      abortus strain RB51 vaccine (RB51). Animals were randomly divided into vaccinated
      and control groups. Ungulates were captured, blood sampled, and swabs taken from
      the nares, rectum, and vagina for bacterial culture on day 0, 42, and 84 post
      inoculation (PI). On day 42, the vaccinated group became a control group and vice
      versa in a crossover design. Blood and swab samples were taken from coyotes on
      days 0, 14, 28, and 42 PI. There was no crossover for the coyote study. Two
      coyotes from each group were also euthanized and cultured for RB51 on days 42,
      84, 168, and 336 PI. Blood samples were analyzed for hematologic changes and
      antibodies to RB51 using a modified dot-blot assay. No morbidity or mortality as
      a result of vaccination was observed in any animal. There were no differences in
      hematologic parameters at any time for ungulate species; vaccinated coyotes had
      higher hematocrit, hemoglobin, and eosinophil counts (P < or = 0.006). All
      individuals, except some moose, seroconverted to RB51. Strain RB51 was cultured
      from oropharyngeal lymph nodes from one coyote 42 days PI and from a moose 117
      days PI. This study suggested that a single oral dose of RB51 was safe in these
      species.

PMID- 12238373
TI  - Effects of diet and body condition on fecal progestagen excretion in elk.
AB  - Recent research demonstrated the utility of fecal progestagens (P4) for detecting
      pregnancy in elk (Cervus elaphus) during mid- to late gestation. Several factors,
      however, may influence fecal P4 excretion and limit its use in free-ranging
      animals. We investigated the effects of nutrition and body condition (percent
      ingesta-free body fat) on fecal P4 concentrations and incidence of abortion.
      During mid-gestation (late December 1997 through early March 1998), 40 gravid cow
      elk varying in body condition were placed on three diets (high, medium, and low)
      in which the amount of food offered varied. Feces were collected periodically and
      analyzed for P4 via radioimmunoassay. We found no significant effect of dietary
      treatment on P4 concentrations, but as body condition declined, P4 concentrations
      declined significantly. This decline did not impede the ability to detect
      pregnancy based on previously reported criteria, even for elk in such poor
      condition that they aborted. However, fecal P4 concentrations in 10% (4/39) of
      samples collected from 13 non-pregnant animals maintained on a high plane of
      nutrition were false-positive for pregnancy. We suggest alternate criteria for
      determining pregnancy in elk using fecal P4 values: > 1.25 micrograms/g feces as
      pregnant, < 1.0 microgram/g feces as non-pregnant, and 1.0-1.25 micrograms/g
      feces as inconclusive. Finally, two cows that aborted did not abort until weeks
      after being classified as emaciated and near death, suggesting that nutrition
      associated abortion in elk may not occur during mid-gestation except under
      extremely harsh conditions.

PMID- 12238374
TI  - Plasma biochemical values from apparently healthy free-ranging polar bears from
      Svalbard.
AB  - To establish reference values for free-ranging polar bears (Ursus maritimus) at
      Svalbard, Norway, plasma samples from 15 females and 20 males were analyzed for
      28 blood biochemistry parameters. Animals were chemically immobilized (Zoletil:
      tiletamine and zolazepam) on land at Barentsoya, Edgeoya, and the eastern coast
      of Spitsbergen in August 1998. All bears were apparently healthy, with ages
      ranging from 1-22 yr. Females had almost two times higher levels of lipase than
      males. Several parameters varied with age. Levels of alkaline phosphatase (ALP)
      and calcium (Ca) decreased with age, being significantly higher in young
      individuals (< 6 yr) compared to middle-aged (6-13 yr) and older bears (> 13 yr).
      Globulin was lower in animals < 6 yr of age than in animals > 13 yr of age, while
      the opposite was the case for albumin. Levels of ALP, Ca, and potassium decreased
      with age. We found no significant changes in total protein correlated to age, but
      total protein levels were higher in obese compared to lean individuals. Further,
      total protein levels were slightly lower and had greater variation compared to
      data from polar bears in captivity, which may reflect food availability for the
      latter group. The mean ratio between urea and creatinine was 10.9 and indicated
      these bears were fasting. These data provide a baseline from which to compare
      biochemical parameters in captive and free-ranging polar bears and will be
      especially valuable for future studies of polar bears at Svalbard.

PMID- 12238375
TI  - Hematology and serum biochemistry values of dusky-footed wood rat (Neotoma
      fuscipes).
AB  - Serum chemistry values and complete blood counts were determined for 36 wild
      dusky-footed wood rats (Neotoma fuscipes) from Sonoma and western Yolo County,
      California (USA) in summer 1999 and spring 2001. All wood rats had adequate body
      condition and were hydrated. Many hematologic and biochemical values were
      comparable to those for house rat (Rattus rattus). There were differences between
      wood rats tested immediately after capture (those from Yolo County) and after a
      week of habituation in the laboratory (Sonoma County). Significant differences
      were noted in red blood cell counts, hemoglobin, hematocrit,
      neutrophil:lymphocyte ratio, glucose, alanine transaminase, aspartate
      aminotransferase, and alkaline phosphatase values. The neutrophil:lymphocyte
      ratio may have been iatrogenically modified in the wood rats tested immediately
      after capture by stress-induced neutrophilia and lymphopenia. Eosinophilia may
      have been associated with parasites such as botflies in four individuals, and
      hyperglycemia in three individuals could have been associated with stress. The
      cause of elevated enzymes in the animals tested after laboratory habituation is
      unclear. The hematologic and biochemical values of these apparently healthy wood
      rats provide valuable baseline information for use in further medical studies
      performed with this species.

PMID- 12238376
TI  - Comparison of hematologic and biochemical reference ranges between captive
      populations of northern bald ibises (Geronticus eremita).
AB  - Hematologic and biochemical reference ranges for two captive populations of
      northern bald ibises (Geronticus eremita) were compared. The first consisted of
      11 birds at an in-situ breeding colony in Birecik, southern Turkey. The second
      consisted of 27 birds housed at the Durrell Wildlife Conservation Trust in
      Jersey, British Channel Isles (UK). Blood samples were collected in February 1992
      by basilic venipuncture under manual restraint. Birecik birds had higher packed
      cell volumes and red blood counts but lower white blood cell and lymphocyte
      counts than Jersey birds. Birecik birds also had higher total protein, albumin,
      total globulin, calcium, phosphorus, blood urea nitrogen, and total bilirubin
      values; higher albumin to globulin ratios; but lower uric acid values and calcium
      to phosphorus ratios than Jersey birds. Finally, Birecik birds had higher lactate
      dehydrogenase but lower gamma glutamyl transferase values than Jersey birds. Male
      Jersey birds had higher calcium and alkaline phosphatase values, but lower white
      blood cell and heterophil counts than female Jersey birds. The apparent
      differences between the two populations are not thought to be biologically
      significant and may be related to diet and state of hydration.

PMID- 12238377
TI  - Hematologic values for tule elk (Cervus elaphus nannodes).
AB  - Hematologic values for 99 tule elk (Cervus elaphus nannodes) from California
      (USA) are presented. These were obtained from individuals from three captures at
      Tomales Point (Point Reyes National Seashore, California) from 1997-98.
      Differences between capture groups were assessed. Greatest differences were
      detected between yearling bulls and cows in December 1998 which may be a
      reflection of age and reproductive status.

PMID- 12238378
TI  - Observations on myiasis by the calliphorid, Bufolucilia silvarum, in the eastern
      American toad (Bufo americanus americanus) from southeastern Wisconsin.
AB  - Larvae of certain species of blowflies (Calliphoridae) cause myiasis in
      amphibians which may result in significant mortality, yet there are few reports
      from North America. In this study, we observed primary myiasis in a population of
      juvenile eastern American toads (Bufo americanus americanus) collected during May
      July 1998 from southeastern Wisconsin (USA). Nine (6%) of 140 toads were infected
      by the green blow fly (Bufolucilia silvarum) with a mean intensity of 10.5 +/-
      7.2 (range = 1-24). Weekly parasite prevalence and mean intensity remained low,
      ranging from 0-20% and 2 +/- 1.4 to 14 +/- 6, respectively. We found: 1) flies
      lay eggs on healthy toads, 2) eggs hatch with first instar maggots penetrating
      under the skin, 3) maggots develop to mature third instars within 5-7 days, 4)
      maggots leave the host and form pupa within 8-11 days of hatching, and 5) maggots
      pupate within 7-9 days at room temperature. All infected toads died within 1-2 wk
      as a result of the infection. The low prevalence observed in this study and other
      reports of this species from mammalian and bird carcasses indicated that B.
      silvarum is probably a facultative parasite of toads and other amphibians in the
      United States. This is the first report of B. silvarum causing myiasis in
      Wisconsin amphibians and the first report in eastern American toads in the United
      States.

PMID- 12238379
TI  - Grey flesh fly (Wohlfahrtia vigil) parasitism of a Preble's meadow jumping mouse
      (Zapus hudsonius preblei).
AB  - A Preble's meadow jumping mouse (Zapus hudsonius preblei) parasitized by five
      grey flesh fly (Wohlfahrtia vigil) larvae was discovered at the United States Air
      Force Academy in Colorado Springs, Colorado (USA), in June 1998. This is the
      first documented case of grey flesh fly parasitism of jumping mice (Family
      Dipodidae). The lesion was approximately 6 mm wide and was partially hidden under
      a mat of wet fur. Myiasis was found in one (0.7%) of 146 jumping mice captured at
      the Academy in 1998. The Preble's meadow jumping mouse is considered a threatened
      subspecies by the United States Fish and Wildlife Service. Although grey flesh
      fly myiasis can be fatal, it is unknown whether it is affecting populations of
      Preble's meadow jumping mouse. This is the first report of grey flesh fly myiasis
      in free-ranging wildlife in Colorado.

PMID- 12238380
TI  - Fatal cytauxzoonosis in a free-ranging bobcat (Lynx rufus).
AB  - In September 2000, a free-ranging bobcat (Lynx rufus) cub was presented to the
      Kansas State University Veterinary Teaching Hospital (Manhattan, Kansas, USA) in
      a moribund state with signs of severe anemia and respiratory difficulty. The cub
      was euthanized. Gross necropsy findings included multifocal atelectasis,
      splenomegaly, and pericardial effusion. Microscopic examination revealed subacute
      pulmonary thrombosis, mild vasculitis in the brain, and large schizont-filled
      macrophages within blood vessels of all tissues examined. The organisms were
      typical of the developmental stages of Cytauxzoon felis. Cytauxzoonosis is
      considered to be a persistent, subclinical infection in the bobcat; however, this
      cub had lesions consistent with those seen in fatal infections in domestic cats.
      This case of fatal C. felis infection indicates that some free-ranging bobcats
      may die of cytauxzoonosis.

PMID- 12238381
TI  - Maxillary lymphosarcoma in a white-tailed deer (Odocoileus virginianus).
AB  - In 1996, lymphosarcoma was observed in a captive adult female white-tailed deer
      (Odocoileus virginianus) from northeastern Kansas (USA). A subcutaneous mass on
      the deer's left cheek was surgically removed and lymphosarcoma was diagnosed. The
      mass recurred within 3 wk. A second surgical removal was attempted but the tumor
      had grown much larger, had become intimately involved with the buccal mucosa, and
      was beginning to interfere with mastication. For these reasons, the deer was
      euthanized. At postmortem examination the only abnormal findings were the primary
      tumor and enlarged ipsilateral parotid and mandibular lymph nodes. Histologically
      these tissues demonstrated changes characteristic of lymphosarcoma but no other
      organs had evidence of neoplastic disease. A diagnosis of focal lymphosarcoma
      with local metastasis was made. The organ distribution of lymphosarcoma in this
      deer differs from previously described cases of lymphosarcoma in cervids.

PMID- 12238382
TI  - Lymphosarcoma in a sea otter (Enhydra lutris).
AB  - Lymphoblastic lymphosarcoma involving the mesenteric lymph node and thymus was
      discovered in a 4 yr old male sea otter (Enhydra lutris). Diagnosis was based on
      gross and light microscopic studies. The cause of this neoplasm was not
      determined. This is the first case of lymphosarcoma reported in sea otters.

PMID- 12238383
TI  - Echinococcus multilocularis in a European beaver from Switzerland.
AB  - Infection with the larval stage of the cestode parasite Echinococcus
      multilocularis was diagnosed in a European beaver (Castor fiber) in central
      Switzerland. The animal was hit, run over by a car, and died of trauma. It was in
      normal body condition and no signs of disease were seen. At necropsy, multiple
      cystic structures up to 1 cm in diameter were found in the liver adjacent to the
      hilus. Within the parasite vesicles, multiple protoscolices were visible. The
      species was determined to be Echinococcus multilocularis by upon polymerase chain
      reaction and direct immunofluorescence with MAbG11-FITC. This is the first report
      of Echinococcus multilocularis in European beaver.

PMID- 12238384
TI  - Cerebral cysticercosis in a woodchuck (Marmota monax).
AB  - A juvenile woodchuck (Marmota monax) with vestibular signs was found in
      Woodbridge, Ontario (Canada) and later euthanized. At necropsy there was marked
      distortion of the right side of the skull, where a large, fluctuant, subcutaneous
      mass extended under the zygomatic arch and caudally from the right eye towards
      the right ear. The mass was multiloculated and contained a large number of
      tapeworm cysticerci, each about 1 to 2 mm in diameter. The third and lateral
      ventricles of the brain were dilated and contained large numbers of similar
      cysticerci. Based on the exogenous budding of cysts and the morphology of the
      scolex in each cyst, they were identified as cysticerci of Taenia crassiceps.
      This is the first report of cerebral cysticercosis in a woodchuck.

PMID- 12238385
TI  - Sarcoptic mange in free-ranging pampas foxes in the Gran Chaco, Bolivia.
AB  - Sarcoptes scabiei infestation was diagnosed in two freshly dead free-ranging
      pampas foxes (Pseudalopex gymnocercus) in the Gran Chaco, Bolivia. Diagnosis was
      made based on histologic evaluation of skin biopsies and identification of the
      parasite from skin scrapings. Characteristic gross lesions consistent with mange
      were noted in 19 of 94 observations of free-ranging pampas foxes in the region
      from December 1998 to January 2000. None of 16 crab-eating foxes (Cerdocyon
      thous) observed during the same time period had visible lesions consistent with
      scabies. These are the first case reports of S. scabiei in pampas foxes.

PMID- 12238386
TI  - Paratuberculosis in free-ranging fallow deer in Spain.
AB  - Paratuberculosis was diagnosed in a population of approximately 1,000 free
      ranging fallow deer (Dama dama) sampled from 1997-98 in the Regional Hunting
      Reserve of El Sueve (Asturias, Spain). Five of eight animals observed with
      diarrhea were diagnosed as having paratuberculosis on the basis of gross lesions
      at postmortem examination and histopathology. In two deer, Mycobacterium avium
      subsp. paratuberculosis was cultured and identified by polymerase chain reaction.
      Indirect enzyme-linked immunosorbent assay and immunodiffusion tests were used to
      evaluate sera from 33 adult deer from this population. All fallow deer tested
      were seronegative.

PMID- 12238387
TI  - Antibodies to adenoviruses in free-living common buzzards from Germany.
AB  - One hundred sixty-seven plasma samples of free-living birds of prey from Berlin
      and Brandenburg State (Germany) were tested for antibodies against avian
      adenovirus (FAV, group I) using agar gel precipitation test. Antibodies to FAV
      were detected in seven (4%) of 167 total samples. The positive samples originated
      only from common buzzards (Buteo buteo; seven [12%] of 59). This serologic survey
      provides evidence of natural exposure of free-living common buzzards from eastern
      Germany to adenoviruses.

PMID- 12238388
TI  - Epididymal cysts in European bison.
AB  - We describe gross and histopathology of cysts found in the epididymis of the
      European bison (Bison bonasus). The material was collected from 107, 3 mo to 20
      yr old, free-ranging, culled males from the Bialowieza Primeval Forest (Poland).
      Epididymal cysts were observed in 65 (61%) of bison of varying ages. They were
      primarily in the head of epididymis and less often in the corpus or tail. The
      cysts contained opalescent fluid devoid of spermatozoa. They were lined by
      epithelium resembling that of efferent ducts and appeared to be congenital
      abnormalities.

PMID- 12238389
TI  - Streptococcus equisimilis infection in striped skunks (Mephitis mephitis) in
      Saskatchewan.
AB  - Three radio-collared striped skunks (Mephitis mephitis) found dead during a field
      study of winter ecology of striped skunks near Willowbrook, Saskatchewan, Canada
      were examined. Streptococcus equisimilis was identified as the primary agent
      causing necrotizing purulent pneumonia in one skunk and suppurative
      meningoencephalitis in another. Both Streptococcus equisimilis and Streptococcus
      canis were isolated from lesions of purulent myocarditis and pyothorax in the
      third skunk. These are apparently the first reported cases of S. equisimilis
      infection in striped skunks and suggest that this opportunistic pathogen may be a
      significant cause of mortality under some conditions.

PMID- 12238390
TI  - Evidence of Helicobacter sp. in dental plaque of captive dolphins (Tursiops
      gephyreus).
AB  - Gastrointestinal lesions have been extensively reported in wild and captive
      marine mammals. However, their etiology remains unclear. In humans and other
      animals, chronic gastritis and peptic ulcers have been associated with
      Helicobacter sp. Therefore, the aim of our study was to investigate the presence
      of Helicobacter sp. in the gastric juice, dental plaque, and saliva of marine
      mammals living in a controlled environment. Five dolphins (Tursiops gephyreus),
      one killer whale (Orcinus orca), one false killer whale (Pseudorca crassidens),
      three sea lions (Otaria flavescens), two elephant seals (Mirounga leonina), and
      two fur seals (Arctocephalus australis) were studied. Saliva, dental plaque, and
      gastric juice samples were examined for Helicobacter sp. using polymerase chain
      reaction. None of the gastric juice or saliva samples were positive for
      Helicobacter sp. However, Helicobacter sp. DNA was detected in dental plaque from
      two dolphins, suggesting the oral cavity might be a reservoir of this bacterium.

PMID- 12238391
TI  - Antibodies to selected viral and bacterial pathogens in European wild boars from
      southcentral Spain.
AB  - Serum samples from 78 European wild boars (Sus scrofa) harvested during the 1999
      2000 hunting season were tested for antibodies to Brucella spp., classical swine
      fever virus, Erysipelothrix rhusiopathiae, Haemophilus parasuis, Leptospira
      interrogans serovar pomona, Mycoplasma hyopneumoniae, pseudorabies virus (PRV),
      porcine parvovirus (PPV), porcine reproductive and respiratory syndrome virus,
      Salmonella serogroups B, C, and D, Streptococcus suis, and swine influenza virus
      (SIV) serotypes H1N1 and H3N2. Samples were collected from Sierra Morena and
      Montes de Toledo in southcentral Spain. Antibodies were detected to PRV (36%), L.
      interrogans serovar pomona (12%), PPV (10%), E. rhusiopathiae (5%), SIV serotype
      H1N1 (4%), Salmonella serogroup B (4%), and Salmonella serogroup C (3%). Our
      results suggest that more research is needed to describe the epidemiology of
      infectious diseases of Spanish wild boars.

PMID- 12238392
TI  - Increased prevalence of Brucella suis and pseudorabies virus antibodies in adults
      of an isolated feral swine population in coastal South Carolina.
AB  - Two hundred twenty seven adult (> 8 mo) feral swine (Sus scrofa) trapped from
      April through July 1999 at three locations on a coastal South Carolina (USA)
      peninsula with restricted ingress and egress were tested for Brucella suis and
      pseudorabies virus (PRV) antibodies. Approximately 44% of the animals tested
      positive for B. suis antibodies and 61% tested positive for antibodies to PRV.
      Previous surveys (1976 and 1992) of feral swine at the same location with similar
      methods indicated lower seroprevalences (28% and 18% for B. suis and 0% and 19%
      for PRV). We also found 39% of feral swine seropositive (n = 179) for Trichinella
      spiralis and 49% seropositive (n = 181) for Toxoplasma gondii. Results of
      repeated sampling demonstrated that seroprevalence to pathogens can increase with
      time in an isolated, unhunted population of feral swine suggesting an increased
      risk to local domestic livestock and potentially to human health.

PMID- 12238393
TI  - [Results of hip surgical reconstruction in congenital dislocation of the hip in
      children].
AB  - The paper presents a series of 51 hips (5 boys, 33 girls) that underwent
      reconstructive surgery because of congenital hip dislocation. Surgical treatment
      involved a one-stage procedure, consisting of correction of the proximal femur
      position and acetabuloplasty. Acetabulum reconstruction was achieved by using one
      of three methods: Pemberton osteotomy, Salter osteotomy and a "shelf-type"
      acetabuloplasty. Excellent and good results were found in 84% of the cases under
      4 years of age, irrespective of the acetabuloplasty implemented.

PMID- 12238394
TI  - [Repair of focal chondral lesions of femoral condyles treated with osteochondral
      autografts].
AB  - A series of 15 patients with focal chondral lesions of the femoral condyles were
      treated at the Orthopaedics Department of the University of Medical Sciences of
      Lublin between 1998-2000. The patients' age varied from 20 to 72 years and the
      follow-up period from 6 months to 2.5 years. Osteochondritis dissecans was
      observed in 9 patients. Articular cartilage defects associated with chronic
      ligament instability was noted in 5 cases and 1 patient suffered from a chondral
      fracture of the lateral femoral condyle during a traumatic luxation of the
      patella. The depth of the lesions was graded according to ICRS scale. Grade IV
      was found in 11 cases and the remaining 4 cases had grade III lesions. The
      defects were treated with osteochondral autografts using OATS instrumentation
      set. Results were prospectively evaluated according to the HSS score. The
      preoperative value of HSS score ranged from 28 to 51 points (average 40.3).
      During follow-up the score values ranged from 76 to 91 points (average 84.7
      points). All patients regained full range of motion in the knee, although in one
      case arthroscopic release of intraarticular adhesions was performed 6 months
      after chondroplasty. The lowest HSS values at follow-up were found in elderly
      patients with concomitant mild degenerative changes in the lateral knee
      compartment and in the patello-femoral joint. All patients had MRI examination
      early post-op, then after 6, 12 and 24 months from the procedure. MRI confirmed
      proper structure of the grafted cartilage but bony parts of the graft did not
      integrate with the surroundings.

PMID- 12238395
TI  - [Surgical treatment of advanced congenital scoliosis with the C-D method].
AB  - The paper presents the results of surgical treatment of 15 cases of congenital
      scolisios with CD instrumentation. Progression of the deformity was most often
      seen in cases with combined deformities (according to the McMaster
      classification). Indications for surgical treatment were progression of the
      curvature and trunk and thorax deformity progression, particularly during the
      growth spurt. The age at the time of surgery ranged from 10.3 to 16 years
      (average: 13.8 years). Follow-up period ranged from 2 to 8 years (average: 4
      years). Intraoperative deformity correction ranged from 0 to 60% (average 32%).
      Loss of correction during follow up ranged from 0 to 3%. The overall silhouette
      improvement was a result of correction of the spine curvature, correction of
      thoracic hyperkiphosis and a decrease of trunk decompensation. The only
      complications noted were 3 cases of transient neurological symptoms from the
      lower extremities. Preoperative MRI allows detection of congenital deformities of
      the spinal canal, a contraindication for surgical correction of the deformity
      with spinal implants.

PMID- 12238396
TI  - [Presence and intensity of the Lasegue sign in relation to the site of lumbar
      intervertebral disc herniation].
AB  - The manouevre of stretching the sciatic nerve known as the Lasegue test is very
      useful in the clinical evaluation of patients with suspicion of lumbar disc
      herniation and has been in use for over 100 years. The relationship between the
      intensity of the Lasegue test and intraoperative localization of disc herniation
      is presented. The material comprised 87 cases (54 males and 33 females) aged 47
      (+/- 9) years. Duration of symptoms was on average 9 months (+/- 7.5 months). The
      Lasegue sign was positive in 84 patients and negative in 3 patients (absent in 1
      case, and more than 70 degrees in 2 cases). In the investigated group the Lasegue
      sign was positive at 39 degrees (+/- 22 degrees) on average. The obtained results
      indicate a strong relation between a positive Lasegue sign and disc herniation
      leading to direct spinal nerve or nerve sheath compression.

PMID- 12238397
TI  - [External fixation of fractures using Dysnastab-S stabilizers for massive ankle
      fractures of tibial bone epiphyseal articulations ].
AB  - Massive ankle fractures lead to joint stiffness and resulting decrease in range
      of motion. This can be avoided by functional treatment. In cases where severe
      soft tissue trauma coexists with bone fractures surgical treatment is limited and
      external fixation is the method of choice. Modern external fixation technique
      allows for stabilisation and maintaining range of motion in the affected joint.
      This paper presents the results of application of the Dynastab-S external
      fixator. The construction of this fixator allows dorsal and plantar, reducing
      postraumatic joint stiffness. It also allows appropriate insight into soft
      tissues and debridement of devitalised tissues as well as their forthcoming
      surgical reconstruction. In our material (27 cases) treated with the Dynastab-S
      fixator for an average of 16 weeks a satisfactory bone healing process in all
      cases was noted. Appropriate function of the extremity was maintained, with
      comparable plantar flexion to the contralateral, not affected joint. Only in one
      case post operative treatment was complicated by algodystrophy. Our observations
      showed that implementation of modern external stabilisation techniques leads to
      appropriate fracture healing with full function of the inferior extremity.

PMID- 12238398
TI  - [Pathologic anatomy of congenital clubfoot--review of the literature and personal
      observations].
AB  - The authors present a review of literature of the past 40 years, relevant to the
      pathological anatomy of congenital clubfoot and their own views--based on intra
      operative observations. Performing Goldner's procedure the authors noted the
      talar bone was rotated internally, as a whole and externally in relation to the
      forefoot. The head and neck of the talar bone were deviated medially in relation
      to the trochlear axis. These deformities lead to pronation and supination
      movements instead of the normal flexion and extension of the foot. The authors
      believe a wide capsulotomy with resection of the ligaments is necessary to
      achieve proper clubfoot correction.

PMID- 12238399
TI  - [Remarks on diagnosis and treatment of cubital tunnel syndrome].
AB  - This review article presents the principles of diagnostics and treatment of
      cubital tunnel syndrome. Indications for treatment of this neuropathy are also
      presented.

PMID- 12238400
TI  - [Cubital tunnel syndrome: evaluation of anterior subcutaneous transposition of
      the ulnar nerve].
AB  - 57 cases of cubital tunnel syndrome were treated by anterior subcutaneous
      transposition of the ulnar nerve. Physical examination showed that ulnar nerve
      function--motor and sensory improved after surgery treatment. Subcutaneous
      transposition is a reliable and effective surgical option.

PMID- 12238401
TI  - [Osteotomy of the navicular bone in scaphoid malunion].
AB  - In scaphoid malunions corrective osteotomy and filling the gap of scaphoid waist
      with bone graft was carried out. Corrective osteotomy of malunion was needed in 2
      cases among 43 waist reconstructions. The size of the gap was assessed
      intraoperatively by carpal stretch test. In both 2 cases bone healing, correction
      of scaphoid angle and pain relief was achieved.

PMID- 12238402
TI  - [Evaluation of Chirulen biopolymer properties based on molecular and super
      molecular structure changes caused by plastic strain and radiation
      sterilization].
AB  - The paper presents an analysis of the effect of plastic strain and sterilization
      treatment by an electron beam as well as the joint effect of both of the two
      external factors on the change of molecular and supermolecular characteristics of
      the Chirulen biopolymer which is used for the production of Weller endoprosthesis
      cups. It has been shown how, due to these influences, the weighted mean molar
      mass, differentiation of macromolecule sizes, crystalline phase fraction and the
      degree of order of polymer internal structure are changing. In terms of such
      changes the effects on the cup material are presented connected with hardness,
      the modulus of elasticity and polymer susceptibility to undurable deformations.
      Simultaneously, conclusions were formed concerning possible biopolymer behaviors
      during endoprosthesis service if the described effects and accompanying
      modification of the internal structure occur.

PMID- 12238403
TI  - [Modern poro-elastic biomechanical model of bone tissue. I. Biomechanical
      function of fluids in bone].
AB  - The modern biomechanical two-phase poroelastic model of bone tissue is presented.
      Bone tissue is treated in this model as a porous elastically deformed solid
      filled with a viscous newtonian fluid. Traditional one-phase biomechanical model
      of bone tissue, which is characterized by the Young modulus and the Poisson's
      coefficient, is still valid and it can be treated as an approximate model in
      comparison with the more realistic two-phase model of bone tissue. The
      biomechanical function of fluids in bone is considered. Bone biodynamics is
      presented in form of the scheme which illustrates the mechano-adaptive, the
      mechano-electric and the electrophysiologic properties of bone tissue. Essentials
      of the poroelastic model of bone tissue is the mechanical load induced flow of
      intraosseous fluid and the associated strain generated electric potentials SGPs.

PMID- 12238404
TI  - [Reconstruction of plantar regions with free radial forearm flaps after frostbite
      of both feet--case report and literature review].
AB  - Treatment of 49 year old male with frostbite of feet is presented. The treatment
      included reconstruction of plantar surfaces in the both feet. Necrotic tissues
      were excised seven weeks after the injury and the wounds were split skin grafted.
      Two staged reconstruction with free neurovascular radial forearm flaps was
      carried out 15 and 20 weeks after the frostbite. The both flaps healed without
      complications. The patient recovered touch sensibility in the flap skin after 6
      months and than he was able to walk. He returned to his professional job. 12
      years after the reconstruction the patient can move freely using orthopedic
      shoes. His full weight bearing time amounts to 3 hours per day. In case of longer
      trips he takes elbow crouches with him just for assecuration. Pain and touch
      sensibility is very good and evenly distributed. 2PD on the plantar surfaces is
      similar and amounts to 12-15 mm. Meticulous feet care decreased hyperkeratosis
      thus preventing pressure sore and ulceration. No complications were observed in
      the donor site.

PMID- 12238405
TI  - [Surgical treatment of old C2 spinal fracture with C2/C3 subluxation using an
      anterior retropharyngeal approach--case report].
AB  - A patient with an inverterate transpedicular fracture of atlas and C2/C3
      subluxation, with stenosis of spinal canal by bone fragment, was operated using
      anterior retropharyngeal approach. Stabilization with interbody cage was
      performed. During follow up examination both clinical and radiological result was
      good. This surgical approach seems to be a comfortable approach to the upper
      cervical spine.

PMID- 12238406
TI  - [Seatbelt syndrome].
AB  - The authors review reference publications and discuss diagnostic intricacies in a
      case of a 7 year old boy with seatbelt syndrome. The syndrome concerns most
      commonly children aged 4 to 9 years. It results from injuries in communication
      accidents--and actuation of two-point seatbelts. Injuries concern both the
      abdominal cavity organs (i.e. intestines, mesentery) and lumbar segments of the
      spine--including Chances's fractures.

PMID- 12238407
TI  - [A case of radial head fracture with disruption of the lateral collateral
      ligament and elbow dislocation].
AB  - The authors present a case of radial head fracture with disruption of the lateral
      collateral ligament and elbow dislocation. Treatment gave a very good result.
      Elbow instability after reduction and radial head fixation is a strong indication
      for ligament repair.

PMID- 12238408
TI  - A cognitive approach to child abuse prevention.
AB  - This investigation tested the incremental utility of cognitive retraining as a
      component within a program designed to prevent child maltreatment. High-risk
      families (N = 96) were randomly assigned to a control condition, home visitation
      modeled after the Healthy Start program (unenhanced home visitation), or home
      visitation that included a cognitive component (enhanced home visitation).
      Mothers were identified late during pregnancy or soon after birth, and their
      participation continued for 1 year. Lower levels of harsh parenting were found
      among mothers in the enhanced home visitation condition than among those in the
      unenhanced home visitation or control conditions. Prevalence of physical abuse
      (percentage of mothers who were abusive) during the first year was 26% in the
      control condition, 23% in the unenhanced home visitation condition, and 4% in the
      enhanced home visitation condition. Benefits were greatest in families that
      included a medically at-risk child. A linear pattern of benefits was found for
      child health; as program features were added, benefits for child health
      increased.

PMID- 12238409
TI  - Interparental aggression and young children's representations of family
      relationships.
AB  - Children's maternal, self, and marital representations were examined in 46
      children 3 1/2 to 7 years old using the MacArthur Story Stem Battery. Children
      drawn from agencies serving battered women expressed fewer positive
      representations of their mothers and themselves, were more likely to portray
      interparental conflict as escalating, and were more avoidant and less coherent in
      their narratives about family interactions than children from a nonviolent
      community sample. Interparental aggression uniquely predicted representations of
      conflict escalation and avoidance after accounting for parent-child aggression,
      and the two types of aggression had additive effects in predicting positive
      maternal representations. The results suggest that witnessing aggression in the
      family affects children's developing beliefs about close relationships and may be
      a process by which these experiences give rise to later problems in social and
      emotional functioning.

PMID- 12238410
TI  - The impact of wife abuse on marital relations as revealed by the Second
      Palestinian National Survey on Violence Against Women.
AB  - This article presents findings on the impact of wife abuse on marital relations,
      as revealed by the Second Palestinian National Survey on Violence Against Women.
      The study was conducted with a systematic random sample of 1,334 Palestinian
      women from the West Bank and the Gaza Strip. The results revealed that compared
      with their nonabused counterparts, abused wives expressed higher levels of
      negative patterns of communication with husbands and lower levels of commitment
      to marriage, marital satisfaction, affection, harmony, and happiness. In
      addition, the results indicated that substantial amounts of the variance in all
      six dimensions of marital relations examined are significantly explained by being
      physically abused, psychologically abused, sexually abused, and/or economically
      abused, over and above the variance explained by women's sociodemographic
      characteristics. Recommendations for further research on this topic in
      Palestinian society are presented.

PMID- 12238411
TI  - Varying forms of husband sexual aggression: predictors and subgroup differences.
AB  - The relationships between two forms of husband sexual aggression (coercion and
      threatened/forced sex) and husband physical and psychological aggression were
      examined among a community sample of 164 couples. A stronger relationship between
      physical and sexual aggression was obtained than in previous research. Husbands'
      physical and psychological aggression predicted husbands' sexual coercion, but
      only physical aggression predicted threatened/forced sex. The more severely
      physically violent subtypes of the A. Holtzworth-Munroe et al. (2000) typology
      engaged in the most sexual coercion, and the most violent subtype (generally
      violent/antisocial) engaged in the most threatened/forced sex. In examining C. M.
      Monson and J. Langhinrichsen-Rohling's (1998) typology, the existence of a
      sexually violent--only subtype was documented, physically nonviolent husbands
      were found to engage in sexual coercion, and sexually and physically violent
      husbands engaged in the highest level of sexual aggression. The utility of using
      multiple measures, and both spouses' reports, to assess sexual aggression is
      emphasized.

PMID- 12238412
TI  - Children's perceptions of the fairness of parental preferential treatment and
      their socioemotional well-being.
AB  - Being the recipient of favored parental treatment has been identified as a
      correlate of enhanced socioemotional well-being. However, knowledge of children's
      perceptions of the legitimacy of preferential treatment may provide a more
      complete understanding of associations between preferential treatment and
      children's socioemotional well-being. The current study investigated whether
      children's well-being varies in accordance with their views about the fairness of
      preferential parental treatment. One hundred thirty-five children (M = 11.74
      years) and their older siblings (M = 14.64 years) were interviewed independently
      about parents' distribution of affection and control. Although the amount of
      preferential control children reported experiencing was related to more
      externalizing behavior problems, lower levels of internalizing behavior problems
      and greater global self-esteem were indicated when children perceived that such
      preferential behaviors were fair.

PMID- 12238413
TI  - Adult sibling expressed emotion and fellow sibling deviance: a new piece of the
      family process puzzle.
AB  - Seventy-three older siblings were assessed in early adulthood with the Five
      Minute Speech Sample (FMSS) measure of expressed emotion. Sibling critical
      expressed emotion was linked with younger brother concomitant and future
      antisocial behavior, substance use, deviant peer association, increased rate of
      criminal arrests, and early onset sexual activity. Siblings of younger brothers
      with behavior problems were also more likely to be critical of, and to report
      negative relationships with, these brothers than were siblings of well-adjusted
      brothers. Sibling critical expressed emotion also predicted younger brothers'
      maladjustment 1-2 years later, after controlling for earlier sibling conflict and
      parent discipline. The findings accentuate the importance of understanding the
      influence of intrafamilial processes in the etiology of behavior problems.

PMID- 12238414
TI  - Development of an empirical typology of African American family functioning.
AB  - This study empirically identified types of African American families. Adolescents
      (N = 111) were assessed on family functioning. With cluster analytic methods, 3
      types of families were identified. The cohesive-authoritative type was above
      average on parental education and income, averaged about 2 children, exhibited a
      high quality of family functioning and high self-esteem in adolescents. The
      conflictive-authoritarian type had average parental education and income, an
      average of 2.7 children, exhibited controlling and rigid discipline, and placed a
      high emphasis on achievement. The defensive-neglectful type was predominately
      headed by single mothers with below average education and income and averaged
      about 3 children. Such families displayed chaotic family processes, and
      adolescents tended to suffer from low self-esteem. The typology exhibited good
      reliability. The implications of the typology are discussed.

PMID- 12238415
TI  - East meets west: ethnic identity, acculturation, and conflict in Asian Indian
      families.
AB  - This study examined the influence of the family on adolescents' acculturation,
      ethnic identity achievement, and psychological functioning. One hundred eighty
      American-born Asian Indian adolescents and one of their immigrant parents
      completed questionnaires assessing their acculturation, ethnic identity, and
      family conflict. Adolescents also completed anxiety and self-esteem measures. The
      results showed that parents' and adolescents' ratings of their self
      identification and ethnic identity were positively associated. Parents who had a
      separated or marginalized style of acculturation reported higher family conflict
      than those who had an integrated or assimilated acculturation style. Adolescents
      reported higher self-esteem, less anxiety, and less family conflict when there
      was no acculturation gap between them and their parents. The findings suggest
      that how parents relate to their natal, as well as to the host, culture has
      direct effects on adolescents' ethnic identity achievement and their
      psychological functioning.

PMID- 12238416
TI  - Relational support in families with adolescents.
AB  - To better understand what determines the support that family members perceive in
      dyadic family relationships, this study tested to what extent the perceiver, the
      partner, their specific relationship, and the family determine perceived support,
      and whether these effects differ for horizontal (i.e., marital and sibling)
      versus vertical (i.e., parent-child) relationships, or for different types of
      perceivers (i.e., parents versus adolescents). Two parents and two adolescents in
      288 Dutch families judged the support perceived from each other. Social relations
      model analysis showed support perceptions to be more determined by the perceiver
      than by the partner, partly relationship specific, partly generation specific,
      and partly family specific. Relationship-specific support and reciprocity are
      more important in horizontal relationships than in vertical ones. Adolescents'
      support perceptions were more perceiver determined than were parents'
      perceptions.

PMID- 12238417
TI  - Support across two generations: children's closeness to grandparents following
      parental divorce and remarriage.
AB  - There has been relatively little research on the role of grandparents as a source
      of support for children during and following their parents' marital transitions.
      In this study, we examined children's contact with and closeness to grandparents
      in different family types (i.e., two biological parents, single mother,
      stepparent). Participants included 155 children from the Avon Brothers and
      Sisters Study. Parent and child interviews and questionnaires regarding the
      children's relationships with maternal and paternal biological and
      stepgrandparents were examined. There were family type differences in rates of
      contact with grandparents as well as children's closeness to grandparents.
      Furthermore, children's and parents' view about these relationships with
      grandparents were modestly correlated, suggesting that children often held
      different views about their closeness to their grandparents than did their
      parents. Greater closeness to grandparents was associated with fewer adjustment
      problems.

PMID- 12238418
TI  - Resource utilization, cost, and health status impacts of coronary stent versus
      "optimal" percutaneous coronary angioplasty: results from the OPUS-I trial.
AB  - In the OPUS-I trial, primary coronary stent implantation reduced 6-month
      composite incidence of death, myocardial infarction, cardiac surgery, or target
      vessel revascularization relative to a strategy of initial PTCA with provisional
      stenting in patients undergoing single vessel coronary angioplasty. The purpose
      of this research was to compare the economic and health status impacts of each
      treatment strategy. Resource utilization data were collected for the 479 patients
      randomized in OPUS-I. Itemized cost estimates were derived from primary hospital
      charge data gathered in previous multicenter trials evaluating coronary stents,
      and adjusted to approximate 1997 Medicare-based costs for a cardiac population.
      Health status at 6 months was assessed using the Seattle Angina Questionnaire
      (SAQ). Initial procedure related costs for patients treated with a primary stent
      strategy were higher than those treated with optimal PTCA/provisional stent
      ($5,389 vs $4,339, P < 0.001). Costs of initial hospitalization were also higher
      for patients in the primary stent group ($9,234 vs $8,434, P < 0.01) chiefly
      because of the cost differences in the index revascularization. Mean 6-month
      costs were similar in the two groups; however, there was a slight cost advantage
      associated with primary stenting. Bootstrap replication of 6-month cost data
      sustained the economic attractiveness of the primary stent strategy. There were
      no differences in SAQ scores between treatment groups. In patients undergoing
      single vessel coronary angioplasty, routine stent implantation improves important
      clinical outcomes at comparable, or even reduced cost, compared to a strategy of
      initial balloon angioplasty with provisional stenting.

PMID- 12238420
TI  - Is direct stent implantation without predilatation safe? Acute and long-term
      outcome.
AB  - Direct stenting could potentially lead to a reduction in dissections, time, and
      restenosis at 6-month follow-up. Using the premounted Palmaz-Schatz Crown stent
      elective stenting was performed without predilatation in 61 consecutive patients
      who were compared with a control group of provisional stenting. All patients
      underwent clinical and angiographic follow-up at 6 months. Direct stenting was
      successful in 81% of patients. In 16% of the patients predilatation was needed.
      In 3% the stent could not be implanted despite predilatation. Stent dislodgment
      occurred in 2% of patients, without embolization. Six-month angiographic follow
      up was performed in 51 (84%) of 61 patients. In the direct stenting group the
      mean preprocedural minimal luminal diameter (MLD) increased from 0.96 +/- 0.47 to
      3.09 +/- 0.54 mm directly after the procedure. At 6-month follow-up the MLD
      measured 2.32 +/- 0.79 mm. In the provisional stenting group the mean MLD
      increased from 0.92 +/- 0.51 to 2.44 +/- 0.58 mm and was 1.84 +/- 0.70 mm at 6
      month follow-up. Restenosis, defined as a diameter stenosis > 50%, occurred in 8%
      of the direct stenting group compared with 28% in the provisional stenting group
      (P < 0.001). Direct coronary stent implantation can be attempted safely and
      efficaciously. The risk of stent loss is low. The initial and long-term
      angiographic results are significantly better as compared with provisional
      stenting. The risk of restenosis is significantly lower.

PMID- 12238419
TI  - Application of a cardiac arrest score in patients with sudden death and ST
      segment elevation for triage to angiography and intervention.
AB  - The aim of this study was to test a previously validated, prognostic, cardiac
      arrest score in patients with ST segment elevation acute myocardial infarction
      (AMI) who suffered a witnessed cardiac arrest and survived to emergency
      department admission. A consecutive series constructed retrospectively from a
      sudden death database (n = 22) of patients with ST segment elevation AMI
      resuscitated from cardiac arrest underwent angiography and angioplasty of the
      culprit vessel within 24 hours of presentation. A cardiac arrest score was
      assigned to each case by explicit criteria present on evaluation. Primary
      outcomes were survival to hospital discharge and the degree of neurological
      recovery during the hospitalization. All patients underwent successful coronary
      angioplasty and 77% received adjunctive intraaortic balloon counterpulsation. The
      overall rate of survival to discharge was 41%. For cardiac arrest scores of 0, 1,
      2, and 3, respectively, the rates of neurologic recovery were 0 (0%) of 4 (95% CI
      0-53%), 3 (50%) of 6 (95% CI 15-85%), 2 (67%) of 3 (95% CI 13-98%), and 9 (100%)
      of 9 (95% CI 72-100%), and the rates of survival to discharge were 0 (0%) of 4,
      (95% CI 0-53%), 2 (33%) of 6 (95% CI 6-74%), 2 (67%) of 3 (95% CI 13-98%), and 9
      (100%) of 9 (95% CI 72-100%), P < 0.01 for both outcomes over ascending scores.
      These results suggest appropriate patients for primary angioplasty after cardiac
      arrest are those with ST segment elevation AMI and an emergency department
      cardiac arrest score of > or = 2, thus predicting a 11 (92%) of 12 (95% CI 65
      100%) chance of survival to discharge.

PMID- 12238421
TI  - Restenosis rates with flexible GFX stents (REFLEX): clinical and angiographic
      results.
AB  - The objective of this prospective, multicenter, observational trial was to
      evaluate the procedural results and longterm outcomes of the flexible AVE GFX
      coronary stent in native coronary lesions. The trial included 137 consecutive
      patients (111 [81%] men, age 63.1 +/- 9.2 years) with one vessel disease (n = 76
      [55.5%]), two vessel disease (n = 31 [22.6%]), and three vessel disease (n = 30
      [21.9%]) with ischemia secondary to a significant denovo lesion (diameter > or =
      3 mm, length < or = 18 mm) in a native coronary artery. Stent deployment was
      successful in 97.8% (134/137) of patients. Angiographic follow-up at 6.1 +/- 1.2
      months was available in 111 (82.8%) of 134 patients. All angiographic images were
      analyzed by an independent core lab. The primary end point was the binary
      restenosis rate. In-hospital major cardiac events occurred in 3.7%. No
      postdischarge major adverse cardiac events occurred, except for one abrupt
      closure (0.7%). Angiographic restenosis was documented in 22 (19.8%) of 111
      patients. The GFX stent is easy to handle with high success and low restenosis
      rates in patients with simple lesions in native coronary arteries and, thus,
      compares favorably with other sophisticated stents.

PMID- 12238422
TI  - Percutaneous suture closure for brachial artery puncture.
AB  - Percutaneous suture closure for femoral artery hemostasis has gained broad use
      over the last few years since its introduction. The appeal of suture closure is
      the immediate and definitive hemostasis that it achieves, even in anticoagulated
      patients. Described is the use of the Perclose Techstar XL 6Fr suture closure
      device for the management of brachial artery puncture after diagnostic and
      therapeutic catheterization. A 6Fr Perclose Techstar device was used for
      hemostasis during ten procedures in eight patients. In addition, 6Fr and 7Fr
      sheaths were used. Hemostasis was achieved in all but one patient, in whom
      hemostasis was not achieved and surgical repair was necessary. The Perclose
      Techstar device is useful for selected patients for achieving brachial arterial
      puncture site hemostasis. The large excursion of the foot of the new closer
      device may not be as applicable in arteries as small as the brachial artery.
      Patients who are obese may be best suited for this approach.

PMID- 12238423
TI  - Effectiveness of cutting balloon angioplasty for small vessels less than 3.0 mm
      in diameter.
AB  - The aim of this study was to evaluate the effectiveness of cutting balloon
      angioplasty (CBA) in small vessels < 3.0 mm in diameter. Included were 166
      patients (175 lesions) treated with CBA (CBA group), and 215 patients (240
      lesions) were treated with plain old balloon angioplasty (POBA group). No
      differences were observed in patient backgrounds or lesion characteristics
      between the two groups. Procedural success rates were similar: 98.3% (CBA) versus
      95.8% (POBA). Coronary dissection rates were also similar: 7.4% in the CBA versus
      5.8% in the POBA group. Severe dissections (types E and F) occurred in 2.5% of
      cases in the POBA group, whereas there was none observed in the CBA group. In
      hospital complications occurred in 3.3% in the POBA group, and in only 0.6% in
      the CBA group. The restenosis rate was 37.5% (CBA group) versus 48.1% (POBA
      group); and in vessels < 2.75 mm, restenosis was significantly lower in the CBA
      group than in the POBA group (36.9% vs 62.7%, P < 0.05). CBA may be a useful
      therapeutic strategy for small vessels, given the absence of severe coronary
      dissection and the significantly lower rate of restenosis compared to POBA.

PMID- 12238424
TI  - Choice of device size and results of transcatheter closure of atrial septal
      defect using the amplatzer septal occluder.
AB  - The impact of device size choice on closure results was analyzed in 138 (101
      females, 37 males; age 0.5-84.0 years) consecutive patients who underwent
      transcatheter closure of the secundum atrial septal defect (ASD) using the
      Amplatzer septal occluder (ASO). The balloon stretched diameter (SD) of ASD was
      19.5 +/- 7.2 mm in 123 patients with single defects, and 20.4 +/- 6.6 mm for the
      largest defects in 15 patients with multiple ASDs. The difference (delta) between
      ASO size chosen for closure and the stretched diameter of the defect was
      calculated and divided into groups: A (delta < -2 mm); B (delta -2.0 to -0.1 mm);
      C (delta = 0); D (delta 0.1-2.0 mm) and E (delta > 2 mm). The results
      demonstrated that immediate and 24-hour complete closure rates were significantly
      higher in patients in groups C and D (P < 0.001). However, at 6-month follow-up,
      the complete closure rates were similar in patients of groups A-D, while patients
      of group E had a lower closure rate of 75%. The complication rates were similar
      in all groups. In conclusion, a choice of a device size identical to or within 2
      mm larger than the SD of the defect should be used to maximize the closure rates
      of ASD using the ASO.

PMID- 12238425
TI  - Anterior myocardial infarction, acute aortic dissection, and anomalous coronary
      artery.
AB  - Acute dissection of the ascending aorta has, on rare occasions, been accompanied
      by myocardial infarction due to the compression of the ostium of a coronary
      artery. Rarer still is the presence of an aortic dissection, myocardial
      infarction, and an anomalous coronary artery. A case is described of a patient
      who survived an acute aortic dissection complicated by anterior myocardial
      infarction due in part to the presence of an anomalous circumflex artery. The
      anatomy, diagnosis, and consequences of aortic dissection are discussed.

PMID- 12238426
TI  - When zebras run with horses: the diagnostic dilemma of acute aortic dissection
      complicated by myocardial infarction.
AB  - In this issue of the Journal, Pinney and Wasserman describe the case of a patient
      who survives acute aortic dissection complicated by occlusion of the left main
      coronary ostium and anterior myocardial infarction (MI), due in part to the
      fortuitous presence of an anomalous left circumflex artery. The case illustrates
      the challenges of diagnosing aortic dissection, even in the current era of
      accurate and rapid aortic imaging, in individuals with concurrent acute MI. These
      comments are focused in this comment on two key aspects of the case: (1) How
      commonly do acute aortic dissections lead to myocardial ischemia and MI? and (2)
      When should clinicians consider ruling out acute aortic dissection in the setting
      of acute MI?

PMID- 12238427
TI  - Septic coronary embolism.
AB  - This report describes a case of a 31-year-old woman with mitral valve
      endocarditis complicated by a septic embolus to a coronary artery.

PMID- 12238428
TI  - Interventional treatment of septic coronary embolism: sailing into uncharted and
      dangerous waters.

PMID- 12238430
TI  - Saphenous vein graft intervention and distal protection: what are we protecting?

PMID- 12238429
TI  - Distal occluder and rheolytic thrombectomy of a saphenous vein graft lesion with
      a large associated thrombus.
AB  - Percutaneous intervention in thrombus-containing lesions is frequently associated
      with complications, including distal embolization and no-reflow. In saphenous
      vein bypass grafts (SVG), friable atheroma and associated thrombus make
      interventions particularly difficult. Distal protection strategies are in
      development, but complete protection with removal of all potentially embolic
      material is challenging. This case illustrates a novel technique using a distal
      occluder balloon and rheolytic thrombectomy followed by stent deployment to treat
      a SVG lesion. This combination therapy was technically feasible, resulted in no
      angiographic complications and normal creatine kinase levels throughout follow
      up, and can be used during high risk SVG interventions.

PMID- 12238431
TI  - Percutaneous coronary intervention versus coronary artery bypass grafting:
      clinical outcomes in multivessel coronary artery disease.
AB  - Revascularization with percutaneous coronary intervention (PCI) or coronary
      artery bypass grafting (CABG) is superior to medical management in reducing
      symptoms and prolonging exercise duration in patients with coronary artery
      disease (CAD). Ten randomized trials have compared the outcomes in percutaneous
      and surgically treated patients with multivessel CAD. The purpose of this article
      was to summarize the results of those trials to make recommendations regarding
      appropriate revascularization strategy.

PMID- 12238432
TI  - Fibrinolytic and mechanical intervention trials in ST elevation acute myocardial
      infarction.

PMID- 12238433
TI  - Rationale and methods for assessment of coronary flow prior to coronary
      intervention: where are we headed?

PMID- 12238435
TI  - Is the new NHS really listening?

PMID- 12238434
TI  - All in a day's consulting. Interview by Nick Lipley.

PMID- 12238436
TI  - Meeting expectations.

PMID- 12238437
TI  - Cultural allies.

PMID- 12238438
TI  - A homing instinct. Interview by Lynne Wallis.

PMID- 12238439
TI  - Measure your leadership skills.

PMID- 12238440
TI  - Consultant nurses. Set for success.

PMID- 12238441
TI  - Working in a war zone. Interview by Lynne Wallis.

PMID- 12238442
TI  - Commentary on: "comprehensive observational assessment: Ia. A systematic,
      quantitative procedure for assessing the behavioral and physiologic state of the
      mouse." Psychopharmacologia (1968) 13: 222-257.

PMID- 12238444
TI  - Into the third decade of AIDS: books on HIV and mental health.

PMID- 12238443
TI  - In sickness and in health: New York joins the National Gay Men's Health Movement.

PMID- 12238445
TI  - Mangia bene! Hearty, hot, and wholesome Italian foods.

PMID- 12238446
TI  - After a suicide: trying to make sense of the senseless.

PMID- 12238447
TI  - Highlights of the 41st Interscience Conference on Antimicrobial Agents and
      Chemotherapy (ICAAC).

PMID- 12238448
TI  - The XIV International AIDS Conference.

PMID- 12238449
TI  - Anti-HIV agents. American-Italian study produces unexpected results.

PMID- 12238450
TI  - Anti-HIV agents. Tenofovir looks good in initial therapy.

PMID- 12238452
TI  - Anti-HIV agents. T-20 shows its potency.

PMID- 12238451
TI  - Anti-HIV agents. Tenofovir and Videx (ddi) EC--some caution required.

PMID- 12238453
TI  - Anti-HIV agents. Efavirenz makes its mark in AIDS.

PMID- 12238454
TI  - Study finds fatigue linked to quality of sleep.

PMID- 12238455
TI  - High liver enzyme levels--a warning about survival?

PMID- 12238456
TI  - Nutrient deficits found in some HIV positive people.

PMID- 12238457
TI  - Low zinc intake linked to reduced survival.

PMID- 12238458
TI  - AIDS threatens to wipe out American Indian tribes.

PMID- 12238459
TI  - AIDS is a puzzle. 9th retrovirus conference.

PMID- 12238460
TI  - The 1st IAS conference on HIV pathogenesis and treatment.

PMID- 12238461
TI  - Should you disclose your HIV status to a potential sexual partner?

PMID- 12238463
TI  - Setting priorities. AHA's new chairman-elect puts disaster preparedness, worker
      retention on agenda.

PMID- 12238462
TI  - HIV summit.

PMID- 12238465
TI  - The state of AIDS at the Barcelona conference.

PMID- 12238464
TI  - Multileveled selection on plasmid replication.
AB  - The replication control genes of bacterial plasmids face selection at two
      conflicting levels. Plasmid copies that systematically overreplicate relative to
      their cell mates have a higher chance of fixing in descendant cells, but these
      cells typically have a lower chance of fixing in the population. Apart from
      identifying the conflict, this mathematical discussion characterizes the
      efficiency of the selection levels and suggests how they drive the evolution of
      kinetic mechanisms. In particular it is hypothesized that: (1) tighter
      replication control is more vulnerable to selfishness; (2) cis-acting replication
      activators are relics of a conflict where a plasmid outreplicated its
      intracellular competitors by monopolizing activators; (3) high-copy plasmids with
      sloppy replication control arise because intracellular selection favors
      overreplication, thereby relieving intercellular selection for lower loss rates;
      (4) the excessive synthesis of cis-acting replication activators and trans-acting
      inhibitors is the result of an arms race between cis selfishness and trans
      retaliations; (5) site-specific recombination of plasmid dimers is equivalent to
      self-policing; and (6) plasmids modify their horizontal transfer to spread
      without promoting selfishness. It is also discussed how replication control may
      be subject to a third level of selection acting on the entire population of
      plasmid-containing cells.

PMID- 12238466
TI  - AIDS 2002 Barcelona: a personal perspective.

PMID- 12238467
TI  - Private sector responses.

PMID- 12238468
TI  - As time goes by (millions die).

PMID- 12238469
TI  - Three million in thirty-six moons.

PMID- 12238470
TI  - Philosophy in the boardroom: Hank takes Barcelona.

PMID- 12238472
TI  - 20 tips for thriving with HIV.

PMID- 12238471
TI  - Physicians under capitation offer more preventive care and health counseling,
      says study.
AB  - A new study shows that physicians in capitated contracts spend less time with
      patients but offer more preventive care and health counseling, a finding that
      debunks the myth that quality care is sacrificed under capitation.

PMID- 12238473
TI  - Clinical trials part II.

PMID- 12238474
TI  - A needle-free delivery of Serostim.

PMID- 12238476
TI  - Sexual terrorist unconcerned with prevention.

PMID- 12238475
TI  - Stigma = dis-empowerment.

PMID- 12238477
TI  - Brain power.

PMID- 12238478
TI  - Win over your staff and build a better practice.

PMID- 12238479
TI  - JHACI: a low-cost, high-impact intervention.

PMID- 12238481
TI  - TherapyEdge and IAPAC collaborate to improve HIV patient outcomes. Web-based
      software designed to support HIV patient management and enhanced clinical
      response.

PMID- 12238480
TI  - Charging forward: leveraging a time of great momentum into concrete progress. 5th
      International Conference on Healthcare Resource Allocation for HIV/AIDS. April 15
      17, 2002, Rio de Janeiro, Brazil.

PMID- 12238482
TI  - "It's what your God, of whatever name, would want you to do..."  Address to the
      African Religious Leaders Assembly on Children and HIV/AIDS in Nairobi, Kenya,
      June 10, 2002.

PMID- 12238483
TI  - Treating depression in the HIV-infected patient.

PMID- 12238484
TI  - Once-daily dosing of HAART: do the benefits outweigh the concerns?

PMID- 12238485
TI  - Mental health. Should HIV-infected parents tell their children? If so, how?

PMID- 12238486
TI  - Court decisions have implications for practice of dentistry.

PMID- 12238487
TI  - Hormone replacement therapy.

PMID- 12238488
TI  - Chaperone-mediated destruction of erbB2: relevance to tyrosine kinase inhibitors.

PMID- 12238492
TI  - APA, advocacy groups disappointed with final regulations on privacy of medical
      records.

PMID- 12238493
TI  - SAMHSA releases annual survey on substance abuse treatment facilities.

PMID- 12238494
TI  - JAMA patient page. Carpal tunnel syndrome.

PMID- 12238495
TI  - Support for grieving parents.

PMID- 12238496
TI  - Horrified by advertisement.

PMID- 12238497
TI  - Learning to love computerized charting.

PMID- 12238498
TI  - Stop announcing JCAHO inspections.

PMID- 12238499
TI  - Choosing the right vascular access device, part I.

PMID- 12238500
TI  - Limited selection of sodium channel blocking toxin-producing bacteria from
      paralytic shellfish toxin-contaminated mussels (Aulacomya ater).
AB  - Paralytic shellfish toxins (PSTs) are sodium channel blocking (SCB) toxins,
      produced by cyanobacteria, as well as by marine dinoflagellates and their
      associated bacteria, and cause serious health and economic concern worldwide. In
      a previous study, approximately 70% of the bacteria enriched from PST
      contaminated shellfish tissue and isolated on marine agar medium were observed to
      produce SCB toxins. In the study reported here, the high percentage of cultivable
      toxigenic bacteria is demonstrated to be obtained through a marked selection on
      marine agar medium. The cultivable as well as the total bacterial diversity
      associated with PST-contaminated shellfish collected from the Magallanes region
      in the south of Chile has been analysed. Approximately 80% of bacterial isolates,
      analysed by restriction analysis of PCR amplified ribosomal DNA (i.e., ARDRA
      fingerprinting), were limited to only two genotypic OTUs (operational taxonomic
      unit). Sequence determination and analysis of the 16S rDNA from representative
      isolates of both OTUs established them to be closely related to species of the
      Psychrobacter genus of the gamma-subclass of the Proteobacteria. The total
      bacterial diversity in the shellfish was further analysed, using a cultivation
      independent strategy of extraction of total DNA from contaminated tissue, PCR
      amplification of bacterial 16S rRNA genes, cloning of the PCR products and
      analysis of the cloned 16S rDNA sequence types by fingerprinting and sequencing.
      Only 2% of the cloned sequence types corresponded to species of the Psychrobacter
      genus. The 16S rDNA sequence types detected clustered with species of the y
      Proteobacteria subclass, the Cytophaga-Flexibacter-Bacteroides (CFB), the
      Fusobacteria and the Firmicutes phyla. The level of diversity observed within the
      libraries of cloned 16S rDNA was markedly greater than that observed among
      isolates obtained through marine agar enrichment cultures from the same shellfish
      tissue. Additionally the predominant cloned 16S rDNA sequence types detected from
      samples of the surrounding seawater demonstrated no correlation with those
      observed in the PST-contaminated mussels.

PMID- 12238501
TI  - What is your diagnosis? Vaginal hyperplasia.

PMID- 12238502
TI  - Immunohistochemical characterisation of the lesions of canine idiopathic
      pericarditis.
AB  - Pericardial tissue was obtained from 14 dogs with idiopathic pericarditis, and
      from three dogs with pericardial effusion associated with neoplastic disease, for
      histopathological assessment and characterisation of infiltrating leucocytes by
      immunohistochemistry. The major pathological change was extensive pericardial
      fibrosis which was generally accompanied by a mixed inflammatory response that
      was of greatest intensity at the cardiac surface of the tissue. Perivascular
      lymphoplasmacytic aggregates were present at the pleural surface and within the
      fibrosed pericardium. There were no features that clearly distinguished the
      samples from dogs with neoplastic disease from dogs with idiopathic pericarditis.
      The pericardial infiltrates were dominated by MAC 387+ monocyte-macrophages and
      plasma cells expressing immunoglobulin (Ig)A or IgG. CD3+ T lymphocytes and major
      histocompatibility complex (MHC) class II+ macrophages were less common, although
      the perivascular aggregates were mixtures of T and B lymphocytes and a proportion
      of fibroblasts expressed MHC class II. There was no vascular pathology or
      deposition of immunoglobulin or complement within vessel walls. These findings
      are consistent with an immune response dominated by humoral effector mechanisms
      (Th2 immunity) but do not clearly support a primary immune-mediated pathogenesis
      for idiopathic pericarditis.

PMID- 12238503
TI  - Canine and feline pyothorax: a retrospective study of 50 cases in the UK and
      Ireland.
AB  - Fifty cases (36 dogs and 14 cats) with a confirmed diagnosis of pyothorax were
      evaluated from five referral institutions in the UK and Ireland. Aetiology,
      clinical presentation, diagnosis, treatment and outcome of all cases were
      examined. The underlying cause of pyothorax was determined in 18 per cent of
      cases. Positive bacteriological cultures of the pleural fluid were obtained in
      68.7 per cent of the animals. Treatment modalities included surgery and medical
      management, involving thoracostomy tube placement, thoracic aspiration, thoracic
      lavage and antimicrobial therapy. A successful outcome was achieved in 86 per
      cent of patients.

PMID- 12238504
TI  - Review of left-to-right shunting patent ductus arteriosus and short term outcome
      in 98 dogs.
AB  - The case records of 98 dogs with a left-to-right shunting patent ductus
      arteriosus (PDA) were reviewed. There were 35 breeds represented, with a female
      to male ratio of 3:1. Forty per cent of the dogs were older than one year at
      initial presentation and 31 per cent had clinical signs attributable to PDA. A
      left heart base continuous murmur of grade IV/VI or higher was noted in 90 per
      cent of the dogs. On electrocardiography, the most common abnormalities were tall
      R waves (63 per cent) and deep QII waves (62 per cent). The radiographic triad of
      dilation of the descending aorta with enlargement of the main pulmonary artery
      segment and left atrium, typical of PDA, was noted in only 26 per cent of cases.
      Two-dimensional (2D) and M-mode echocardiography detected left atrial enlargement
      (35 per cent) and an increased left ventricular diameter in diastole (82 per
      cent) and systole (84 per cent) as the most common abnormalities. Doppler
      echocardiography demonstrated increased aortic outflow velocities in 66 per cent
      of cases. The overall short-term successful outcome in this study was 95 per
      cent. There was no significant difference between surgical ductal ligation using
      a standard technique or the Jackson-Henderson technique in terms of survival,
      occurrence of haemorrhage or residual shunting. The number of interventional
      procedures used in this study was too low for statistical comparison, but there
      appeared to be a trend towards a higher rate of residual shunting and a lower
      fatality rate using a coil occlusion technique.

PMID- 12238505
TI  - Hypereosinophilic paraneoplastic syndrome in a cat with intestinal T cell
      lymphosarcoma.
AB  - A 10-year-old, neutered female, domestic shorthair cat was presented with a
      recent history of weight loss, polydipsia, diarrhoea and vomiting. On physical
      examination, intestinal thickening and mesenteric lymph node enlargement were
      apparent. Clinical investigations revealed peripheral blood eosinophilia,
      eosinophilic abdominal effusion and eosinophilic mesenteric lymphadenitis. There
      was a temporary response to treatment with glucocorticoids but signs progressed
      and the cat was euthanased. On histology, there was eosinophilic infiltration and
      fibroplasia of intestine and mesenteric lymph nodes. Large aggregates of
      neoplastic round cells in the intestine and lymph nodes were identified as T
      lymphocytes using immunohistochemistry. A diagnosis of intestinal T cell
      lymphosarcoma was made. This case demonstrates that hypereosinophilic
      paraneoplastic syndrome may occur in cats with lymphosarcoma. Eosinophil
      chemotaxis may be a response to the production of interleukin-5 by neoplastic
      lymphocytes.

PMID- 12238507
TI  - Idiopathic hepatic veno-occlusive disease causing Budd-Chiari-like syndrome in a
      cat.
AB  - Budd-Chiari-like syndrome (BCLS) is a rare clinical entity characterised by
      portal hypertension and ascites. This report describes a case of BCLS in a cat
      due to obstruction at the level of the hepatic veins. The diagnosis was based on
      the clinical findings and a histopathological assessment of the liver
      demonstrating perivenular fibrosis around the central and sublobular veins.
      Although these lesions are similar to those observed in man with BCLS, the
      aetiology in this case remains unknown.

PMID- 12238506
TI  - Fluorangiographic alterations in a dog with suspected iatrogenic partial carotid
      artery occlusion.
AB  - During routine fluorescein angiography, a healthy female dog demonstrated
      abnormal delayed filling of retinal and choroidal vessels. Fluorangiographic
      times were increased four- to fivefold with respect to reference values.
      Fluorescein angiography, using the same protocol, was repeated two weeks later
      and a fluorangiogram within reference values was obtained. The abnormal results
      in the first procedure were suspected to have resulted from partial occlusion of
      the carotid artery secondary to the restraining method used.

PMID- 12238508
TI  - Effects of vincristine treatment on semen quality in a dog with a transmissible
      venereal tumour.
AB  - The effect of vincristine treatment on semen parameters in a male boxer with a
      genital transmissible venereal tumour are described. The dog was treated with
      vincristine intravenously at 0.5 to 0.7 mg/m2 body surface area per week for six
      weeks until complete regression of the tumour occurred. Semen samples were
      collected before each application and then at weeks 10, 12, 17, 21 and 23 after
      the start of therapy. There were no alterations in libido or in testicular size
      and consistency either during or after treatment. Total sperm count decreased to
      abnormally low values during weeks 4 and 5, and then began to increase up to
      pretreatment values. No significant alterations in the other semen parameters
      were found during the study period.

PMID- 12238509
TI  - Preparing for pet travel between the UK and North America.

PMID- 12238511
TI  - 'Teacher's pet'--a successful formula for National Pet Week.

PMID- 12238510
TI  - A forum for veterinary emergency care.

PMID- 12238512
TI  - All change on the WSAVA Executive Board.

PMID- 12238513
TI  - Cultural variation of perceptions of crew behaviour in multi-pilot aircraft.
AB  - As the "last line of defence" pilots in commercial aviation often have to
      counteract effects of unexpected system flaws that could endanger the safety of a
      given flight. In order to timely detect and mitigate consequences of latent or
      active failures, effective team behaviour of the crew members is an indispensable
      condition. While this fact is generally agreed in the aviation community, there
      seems to be a wide range of concepts how crews should interact most effectively.
      Within the framework of the European project JARTEL the cultural robustness of
      evaluations of crew behaviour was examined. 105 instructor pilots from 14
      different airlines representing 12 European countries participated in this
      project. The instructors' evaluations of crew behaviours in eight video scenarios
      will be compared in relation to cultural differences on Hofstede's dimensions of
      Power Distance and Individualism.

PMID- 12238514
TI  - Effects of characteristics of image quality in an immersive environment.
AB  - Image quality issues such as field of view (FOV) and resolution are important for
      evaluating "presence" and simulator sickness (SS) in virtual environments (VEs).
      This research examined effects on postural stability of varying FOV, image
      resolution, and scene content in an immersive visual display. Two different
      scenes (a photograph of a fountain and a simple radial pattern) at two different
      resolutions were tested using six FOVs (30, 60, 90, 120, 150, and 180 deg.). Both
      postural stability, recorded by force plates, and subjective difficulty ratings
      varied as a function of FOV, scene content, and image resolution. Subjects
      exhibited more balance disturbance and reported more difficulty in maintaining
      posture in the wide-FOV, high-resolution, and natural scene conditions.

PMID- 12238515
TI  - Construction of an AFLP genetic map with nearly complete genome coverage in Pinus
      taeda.
AB  - De novo construction of complete genetic linkage maps requires large mapping
      populations, large numbers of genetic markers, and efficient algorithms for
      ordering markers and evaluating order confidence. We constructed a complete
      genetic map of an individual loblolly pine (Pinus taeda L.) using amplified
      fragment length polymorphism (AFLP) markers segregating in haploid
      megagametophytes and PGRI mapping software. We generated 521 polymorphic
      fragments from 21 AFLP primer pairs. A total of 508 fragments mapped to 12
      linkage groups, which is equal to the Pinus haploid chromosome number. Bootstrap
      locus order matrices and recombination matrices generated by PGRI were used to
      select 184 framework markers that could be ordered confidently. Order support was
      also evaluated using log likelihood criteria in MAPMAKER. Optimal marker orders
      from PGRI and MAPMAKER were identical, but the implied reliability of orders
      differed greatly. The framework map provides nearly complete coverage of the
      genome, estimated at approximately 1700 cM in length using a modified estimator.
      This map should provide a useful framework for merging existing loblolly pine
      maps and adding multiallelic markers as they become available. Map coverage with
      dominant markers in both linkage phases will make the map useful for subsequent
      quantitative trait locus mapping in families derived by self-pollination.

PMID- 12238516
TI  - Simulated microgravity [bed rest] has little influence on taste, odor or
      trigeminal sensitivity.
AB  - Anecdotal evidence suggests that astronauts' perceptions of foods in space flight
      may differ from their perceptions of the same foods on Earth. Fluid shifts toward
      the head experienced in space may alter the astronauts' sensitivity to odors and
      tastes, producing altered perceptions. Our objective was to determine whether
      head-down bed rest, which produces similar fluid shifts, would produce changes in
      sensitivity to taste, odor or trigeminal sensations. Six subjects were rested
      three times prior to bed rest, three times during bed rest and two times after
      bed rest to determine their threshold sensitivity to the odors isoamylbutyrate
      and menthone, the tastants sucrose, sodium chloride, citric acid, quinine and
      monosodium glutamate, and to capsaicin. Thresholds were measured using a modified
      staircase procedure. Self-reported congestion was also recorded at each test
      time. Thresholds for monosodium glutamate where slightly higher during bed rest.
      None of the other thresholds were altered by bed rest.

PMID- 12238517
TI  - Identification of complex flows in Taylor-Couette counter-rotating cavities.
AB  - The transition in confined rotating flows is a topical problem with many
      industrial and fundamental applications. The purpose of this study is to
      investigate the Taylor-Couette flow in a finite-length cavity with counter
      rotating walls, for two aspect ratios L=5 or L=6. Two complex regimes of wavy
      vortex and spirals are emphasized for the first time via direct numerical
      simulation, by using a three-dimensional spectral method. The spatio-temporal
      behavior of the solutions is analyzed and compared to the few data actually
      available.

PMID- 12238518
TI  - Solar Particle Events from a risk management perspective.
AB  - Solar Particle Events pose a health risk to astronauts in space. Today, SPE
      forecasts are inadequate to provide advance warning with sufficient credibility
      to lead operators to initiate protective measures. However, research on SPEs and
      Coronal Mass Ejections suggests that the space weather community is on the verge
      of substantial improvements in understanding solar energetic particle
      acceleration and propagation. This paper describes the impact of SPEs, reviews
      the physics of SPEs, discusses current SPE forecast tools, and describes an
      approach to provide the comprehensive space weather data necessary to implement
      physics-based SPE risk management.

PMID- 12238519
TI  - A model of cerebellar computations for dynamical state estimation.
AB  - The cerebellum is a neural structure that is essential for agility in vertebrate
      movements. Its contribution to motor control appears to be due to a fundamental
      role in dynamical state estimation, which also underlies its role in various non
      motor tasks. Single spikes in vestibular sensory neurons carry information about
      head state. We show how computations for optimal dynamical state estimation may
      be accomplished when signals are encoded in spikes. This provides a novel way to
      design dynamical state estimators, and a novel way to interpret the structure and
      function of the cerebellum.

PMID- 12238520
TI  - Discriminability measures for predicting readability of text on textured
      backgrounds.
AB  - Several discriminability measures were examined for their ability to predict
      reading search times for three levels of text contrast and a range of backgrounds
      (plain, a periodic texture, and four spatial-frequency-filtered textures created
      from the periodic texture). Search times indicate that these background
      variations only affect readability when the text contrast is low, and that
      spatial frequency content of the background affects readability. These results
      were not well predicted by the single variables of text contrast (Spearman rank
      correlation = -0.64) and background RMS contrast (0.08), but a global masking
      index and a spatial-frequency-selective masking index led to better predictions (
      0.84 and -0.81, respectively).

PMID- 12238521
TI  - Visual detection of spatial contrast patterns: evaluation of five simple models.
AB  - The ModelFest Phase One dataset is a collection of luminance contrast thresholds
      for 43 two-dimensional monochromatic spatial patterns confined to an area of
      approximately two by two degrees. These data were collected by a collaboration
      among twelve laboratories, and were designed to provide a common database for
      calibration and testing of spatial vision models. Here I report fits of the
      ModelFest data with five models: Peak Contrast, Contrast Energy, Generalized
      Energy, a Gabor Channels model, and a Discrete Cosine Transform model. The Gabor
      Channels model provides the best fit, though the other, simpler models, with the
      exception of Peak Contrast, provide remarkably good fits as well. Though there
      are clear individual differences, regularities in the data suggest the
      possibility of constructing a standard observer for spatial vision.

PMID- 12238522
TI  - Modeling of two-phase flow in membranes and porous media in microgravity as
      applied to plant irrigation in space.
AB  - In traditional applications in soil physics it is convention to scale porous
      media properties, such as hydraulic conductivity, soil water diffusivity, and
      capillary head, with the gravitational acceleration. In addition, the Richards
      equation for water flux in partially saturated porous media also contains a
      gravity term. With the plans to develop plant habitats in space, such as in the
      International Space Station, it becomes necessary to evaluate these properties
      and this equation under conditions of microgravitational acceleration. This
      article develops models for microgravity steady state two-phase flow, as found in
      irrigation systems, that addresses critical design issues. Conventional
      dimensionless groups in two-phase mathematical models are scaled with gravity,
      which must be assigned a value of zero for microgravity modeling. The use of
      these conventional solutions in microgravity, therefore, is not possible. This
      article therefore introduces new dimensionless groups for two-phase models. The
      microgravity models introduced here determined that in addition to porous media
      properties, important design factors for microgravity systems include applied
      water potential and the ratio of inner to outer radii for cylindrical and
      spherical porous media systems.

PMID- 12238523
TI  - Design parameters for rotating cylindrical filtration.
AB  - Rotating cylindrical filtration displays significantly reduced plugging of filter
      pores and build-up of a cake layer, but the number and range of parameters that
      can be adjusted complicates the design of these devices. Twelve individual
      parameters were investigated experimentally by measuring the build-up of
      particles on the rotating cylindrical filter after a fixed time of operation. The
      build-up of particles on the filter depends on the rotational speed, the radial
      filtrate flow, the particle size and the gap width. Other parameters, such as
      suspension concentration and total flow rate are less important. Of the four
      mechanisms present in rotating filters to reduce pore plugging and cake build-up,
      axial shear, rotational shear, centrifugal sedimentation and vortical motion, the
      evidence suggests rotational shear is the dominant mechanism, although the other
      mechanisms still play minor roles. The ratio of the shear force acting parallel
      to the filter surface on a particle to the Stokes drag acting normal to the
      filter surface on the particle due to the difference between particle motion and
      filtrate flow can be used as a non-dimensional parameter that predicts the degree
      of particle build-up on the filter surface for a wide variety of filtration
      conditions.

PMID- 12238524
TI  - Integrated CMOS photodetectors and signal processing for very low-level chemical
      sensing with the bioluminescent bioreporter integrated circuit.
AB  - We report an integrated CMOS microluminometer optimized for the detection of low
      level bioluminescence as part of the bioluminescent bioreporter integrated
      circuit (BBIC). This microluminometer improves on previous devices through
      careful management of the sub-femtoampere currents, both signal and leakage, that
      flow in the front-end processing circuitry. In particular, the photodiode is
      operated with a reverse bias of only a few mV, requiring special attention to the
      reset circuitry of the current-to-frequency converter (CFC) that forms the front
      end circuit. We report a sub-femtoampere leakage current and a minimum detectable
      signal (MDS) of 0.15 fA (1510 s integration time) using a room temperature 1.47
      mm2 CMOS photodiode. This microluminometer can detect luminescence from as few as
      5000 fully induced Pseudomonas fluorescens 5RL bacterial cells.

PMID- 12238525
TI  - Virtual humans for validating maintenance procedures.

PMID- 12238526
TI  - Structure of the coding region and mRNA variants of the apyrase gene from pea
      (Pisum sativum).
AB  - Partial amino acid sequences of a 49 kDa apyrase (ATP diphosphohydrolase, EC
      3.6.1.5) from the cytoskeletal fraction of etiolated pea stems were used to
      derive oligonucleotide DNA primers to generate a cDNA fragment of pea apyrase
      mRNA by RT-PCR and these primers were used to screen a pea stem cDNA library. Two
      almost identical cDNAs differing in just 6 nucleotides within the coding regions
      were found, and these cDNA sequences were used to clone genomic fragments by PCR.
      Two nearly identical gene fragments containing 8 exons and 7 introns were
      obtained. One of them (H-type) encoded the mRNA sequence described by Hsieh et
      al. (1996) (DDBJ/EMBL/GenBank Z32743), while the other (S-type) differed by the
      same 6 nucleotides as the mRNAs, suggesting that these genes may be alleles. The
      six nucleotide differences between these two alleles were found solely in the
      first exon, and these mutation sites had two types of consensus sequences. These
      mRNAs were found with varying lengths of 3' untranslated regions (3'-UTR). There
      are some similarities between the 3'-UTR of these mRNAs and those of actin and
      actin binding proteins in plants. The putative roles of the 3'-UTR and
      alternative polyadenylation sites are discussed in relation to their possible
      role in targeting the mRNAs to different subcellular compartments.

PMID- 12238527
TI  - Near-infrared diode laser based spectroscopic detection of ammonia: a comparative
      study of photoacoustic and direct optical absorption methods.
AB  - A photoacoustic spectroscopic (PAS) and a direct optical absorption spectroscopic
      (OAS) gas sensor, both using continuous-wave room-temperature diode lasers
      operating at 1531.8 nm, were compared on the basis of ammonia detection.
      Excellent linear correlation between the detector signals of the two systems was
      found. Although the physical properties and the mode of operation of both sensors
      were significantly different, their performances were found to be remarkably
      similar, with a sub-ppm level minimum detectable concentration of ammonia and a
      fast response time in the range of a few minutes.

PMID- 12238528
TI  - Comparative study of bis(benzyl)phosphate triesters of 2',3'-dideoxy-2',3'
      didehydrothymidine (d4T) and cyclosal-d4TMP--hydrolysis, mechanistic insights and
      anti-HIV activity.
AB  - A comparative study of three cycloSal-d4TMP 1, 2 and 3 and a variety of
      bis(benzyl) phosphate triester 4-8 of the antivirally active nucleoside analogue
      2',3'-dideoxy-2',3'-didehydrothymidine (d4T) will be described. This study has
      been initiated by the observation that the introduction of a simple 7-methyl
      group in the cycloSal-structure (2) led to a completely different hydrolysis
      pattern as compared to the prototype cycloSal-d4TMP 1. Instead of the selective
      formation of d4TMP, a phenyl phosphate diester was formed in the case of the 7
      methyl-substituted compound 2. The difference in degradation pathway was caused
      by a change of the reaction mechanism. The phenyl phosphate diester was
      chemically and enzymatically inert to further cleavage to yield d4TMP. For
      comparison bis(benzyl)-d4TMP 4, bis(alpha-methylbenzyl)-d4TMP 5, bis(alpha
      methoxycarbonylmethyl [MCM]-benzyl)-d4TMP 6 as well as the enzyme-cleavable bis(4
      acetoxybenzyl)-d4TMP [bis(AB)-d4TMP(7 and bis(alpha-methoxycarbonylmethyl-4
      acetoxybenzyl)-d4TMP [bis(alpha-MCM-AB)-d4TMP] 8 were synthesized. Chemical
      hydrolysis studies proved that all bis(benzyl) triesters hydrolyze to give the
      intermediate benzyl phosphate diesters. Moreover, the latter two triesters 7,8
      and cycloSal-d4TMPs 1 and 3 led finally to the delivery of d4TMP. The chemical
      hydrolysis studies allowed a detailed mechanistic interpretation of the
      degradation pathways of triesters 1-8. Cell extract studies of the bis(benzyl)
      triesters 4-8 confirmed that only triesters 7 and 8 released d4TMP although with
      a considerable increase of the reaction rate. Anti-HIV evaluation of the
      compounds showed that cycloSal-d4TMP 1 and the bis(AB) triesters 7,8 were
      entirely independent of the presence of cellular thymidine kinase (TK).

PMID- 12238529
TI  - Molecular mechanism of DApd/DXG against zidovudine- and lamivudine- drug
      resistant mutants: a molecular modelling approach.
AB  - In order to understand molecular mechanism of antiviral drug resistance of HIV-1
      reverse transcriptase (RT) as well as potent antiviral activity of 2,6
      diaminopurine dioxolane (DAPD) [prodrug of (-)-beta-D-dioxolane guanine (DXG)]
      against drug-resistant RTs, molecular modelling studies of three structurally
      distinct nucleoside RT inhibitor (NRTI)-triphosphates (TP) [zidovudine (AZT)-TP,
      lamivudine (3TC)-TP and DXG-TP] complexed with the wild-type (WT) and mutated RT
      were conducted. The computational analyses indicated that the antiviral activity
      and the calculated relative binding energy of the RT inhibitor triphosphates can
      be correlated, and the minimized structures gave information on the molecular
      mechanism of drug resistance conferred by mutations. The interactions between the
      NRTI-TP and adjacent amino acid residues (Lys65, Lys70, Arg72, Tyr115 and/or
      Gln151) played important roles in stabilizing the enzyme-inhibitor complex.
      Particularly, Arg72 was found to stabilize the dioxolane and oxathiolane sugar
      moiety through hydrogen bonding, which was responsible for favourable binding
      affinity of DXG-TP to AZT- as well as 3TC-resistant mutants. The conformational
      changes in these amino acid residues caused by mutation always affected the
      changes in the tertiary structures of enzyme-inhibitor complexes through either
      closing or opening the gap between the fingers and palm domains. The enzyme
      inhibitor complexes with good binding affinity showed tight binding modes by
      closing the gap between the two domains, whereas weak inhibitors gave open and
      loose complexes.

PMID- 12238530
TI  - Aryl-substituted and benzo-annulated cyc/osal-derivatives of 2',3'-dideoxy-2',3'
      didehydrothymidine monophosphate--correlation of structure, hydrolysis properties
      and anti-HIV activity.
AB  - The synthesis of phenyl-substituted and benzoannulated cycloSal phosphate
      triesters of the nucleoside analogue 2',3'-dideoxy-2',3'-didehydrothymidine (d4T,
      Zerit) as lipophilic, membrane-soluble pronucleotides is described. The cycloSal
      moiety was introduced by using cyclic chlorophosphite agents prepared from phenyl
      substituted saligenin derivatives and ortho-hydroxymethylated naphthols,
      respectively. Hydrolysis studies (HPLC analysis) of the triesters 2, 3 showed a
      range of hydrolytic stability from 1.4 h up to 5.1 h and the stability could be
      correlated with the substitution pattern in the cycloSal moiety. A slight
      decrease of their stability was observed, if phenyl-substituted derivatives were
      hydrolyzed in human CEM/O cell extracts. D4T and thymine, possible products of
      enzymatic cleavage of the pronucleotides, were not detected in the cell extracts.
      A further investigation of the hydrolysis process was performed by 31P-NMR
      spectroscopy. This technique allowed a precise monitoring of the degradation
      products and the exact determination of the product ratio. Finally, the newly
      synthesized compounds were tested concerning their antiviral activity against HIV
      in vitro. A strong correlation of the hydrolysis properties and the antiviral
      activity was found. 3-phenyl-cycloSal-d4TMP showed a threefold increase in its
      anti-HIV-1 activity and retained full activity in thymidine kinase (TK) deficient
      cells, indicative of a successful TK-bypass.

PMID- 12238531
TI  - Synthesis and antiherpesvirus activities of 5-alkyl-2-thiopyrimidine nucleoside
      analogues.
AB  - Twenty 5-alkyl-2-thiopyrimidine nucleosides were newly synthesized and examined
      for antiviral activities against herpes simplex virus (HSV), varicella-zoster
      virus (VZV) and human cytomegalovirus (HCMV). In this study, 2'-deoxy-5-alkyl-2
      thiocytidine analogues had lower 50% effective concentration (EC50) values
      against HSV-1, and 2'-deoxy-5-alkyl-2-thiouridine analogues showed lower EC50
      against VZV than their congeners of arabinoside form. Among the compounds
      examined, 2'-deoxy-5-ethyl and 5-propyl-2-thiocytidine (TN-53 and TN-54) were
      most potent and selective anti-HSV compounds. Their EC50s were 0.04 and 0.15
      microM, and selectivity indexes were more than 7,215 and 1,849, respectively. On
      the other hand, 2'-deoxy-5-propyl-2-thiouridine (TN-51), 5-bromovinyl-2
      thiouracil arabinoside (TN-65) and 5-styryl-2-thiouracil arabinoside (TN-67) were
      most potent and selective anti-VZV compounds. Their EC50s were 3.1, 3.8 and 2.6
      pM for CaQu strain of VZV, respectively, and 2.1 to 3.0 times lower than that of
      acyclovir. All 2-thiopyrimidine nucleoside analogues did not show antiviral
      activities against thymidine kinase (TK) negative strains of HSV-1 and VZV. Only
      three 2-thiocytosine arabinoside compounds showed marginal anti-CMV activities
      (EC50s were 57-159 pM). All of the five alkyl-2-thio-pyrimidine nucleoside
      analogues examined were not cytotoxic to human lymphoblastoid cells (RPM18226)
      and human embryonic fibroblast cells (MRC-5) at 240 microM (100 microg/ml) or
      more. Regarding the structure-activity relationship of 5-alkyl-2-thiopyrimidine
      nucleoside analogues, the following remarks will be noted. Elongation of 5-alkyl
      chain (methyl to ethyl) of 2-thiocytosine in both deoxyribosyl and arabinosyl
      nucleosides increased anti-HSV-1 activity but not anti-VZV activity. Furthermore,
      elongation of the same chain (ethyl to propyl) of 2-thiodeoxyuridine increased
      anti-VZV activity whereas it did not in the case of 2-thiouracil arabinosides.

PMID- 12238532
TI  - Novel DL-galactan hybrids from the red seaweed Gymnogongrus torulosus are potent
      inhibitors of herpes simplex virus and dengue virus.
AB  - A novel series of DL-galactan hybrids extracted from the red seaweed Gymnogongrus
      torulosus, was evaluated for its in vitro antiviral properties against herpes
      simplex virus type 2 (HSV-2) and dengue virus 2 (DEN-2). These compounds were
      very active against both viruses with inhibitory concentration 50% (IC50) values
      in the range 0.6-16 microg/ml for HSV-2 and 0.19-1.7 microg/ml for DEN-2,
      respectively, as determined in a virus plaque reduction assay in Vero cells. The
      DL-galactans lacked of cytotoxic effects, on stationary as well as on actively
      dividing cells, and anticoagulant properties. Some of the compounds showed a
      variable level of direct inactivating effect on both virions, with virucidal
      concentration 50% values exceeding the IC50s obtained by plaque reduction assay.
      Full inhibitory activity was achieved when the galactans were present during
      virus adsorption period, suggesting that the mode of action of these compounds is
      an interference in the binding of the surface envelope glycoprotein with the cell
      receptor.

PMID- 12238533
TI  - Alkyloxyphenyl furano pyrimidines as potent and selective anti-VZV agents with
      enhanced water solubility.
AB  - We have previously reported bicyclic furanopyrimidines as potent and selective
      inhibitors of varicella zoster virus (VZV) with subnanomolar activity for p
      alkylphenyl substituted analogues. These compounds are highly lipophilic and of
      limited water solubility. In an effort to address this issue, and with a view to
      oral dosing, we have sought to enhance water solubility whilst retaining high
      antiviral potency and we herein report a novel series of p-alkyloxyphenyl
      compounds which contain a phenolic ether atom intended to boost hydrophilicity.
      We report the synthesis, characterisation and antiviral evaluation of this series
      and note the retention of extremely high antiviral potency, with EC50 values as
      low as 1 nanomolar.

PMID- 12238534
TI  - Injuries and illnesses among New York City Fire Department rescue workers after
      responding to the World Trade Center attacks.
AB  - Within minutes of the terrorist attacks on September 11, 2001, the Fire
      Department of New York City (FDNY) operated a continuous rescue/recovery effort
      at the World Trade Center (WTC) site. Medical officers of FDNY Bureau of Health
      Services (FDNY-BHS) responded to provide emergency medical services (see box).
      The collapse of the WTC towers and several adjacent structures resulted in a
      vast, physically dangerous disaster zone. The height of the WTC towers produced
      extraordinary forces during their collapse, pulverizing considerable portions of
      the buildings' structural components and exposing first responders and civilians
      to substantial amounts of airborne particulate matter. Fires burned continuously
      under the debris until mid-December 2001. Because of ongoing fire activity and
      the large numbers of civilians and rescue workers who were killed during the
      attacks, approximately 11,000 FDNY firefighters and many emergency medical
      service (EMS) personnel worked on or directly adjacent to the rubble and incurred
      substantial exposures (Figure). This report describes morbidity and mortality in
      FDNY rescue workers during the 11-month period after the WTC attacks and
      documents a substantial increase in respiratory and stress-related illness
      compared with the time period before the WTC attacks. These findings demonstrate
      the need to provide acute and long-term medical monitoring, treatment, and
      counseling to FDNY rescue workers exposed to this disaster and to solve supply,
      compliance, and supervision problems so that respiratory protection can be
      rapidly provided at future disasters.

PMID- 12238535
TI  - Community needs assessment of lower Manhattan residents following the World Trade
      Center attacks--Manhattan, New York City, 2001.
AB  - On September 11, 2001, terrorists attacked and destroyed the World Trade Center
      (WTC) in New York City (NYC). An estimated 2,819 persons were reported killed in
      the attacks; many others were injured (Office of the Chief Medical Examiner, New
      York City Department of Health and Mental Hygiene [NYCDOHMH], unpublished data,
      2002). An estimated 25,000 persons living nearby in lower Manhattan were affected
      both physically and emotionally. Many persons witnessed the attacks; lost family
      and friends; were exposed to smoke, dust, and debris; and evacuated their homes.
      To identify the health-related needs and concerns of persons residing near the
      attack site, NYCDOHMH, in collaboration with CDC, surveyed persons residing in
      areas immediately surrounding the WTC site. The primary purpose of the survey was
      to gather information to set priorities and direct public health interventions.
      This report summarizes findings from the assessment, which indicate that a large
      proportion of respondents had physical and psychological symptoms potentially
      associated with the exposure and needed information to address their health and
      safety concerns. On the basis of the results of the survey, NYCDOHMH responded to
      resident concerns, helped reduce exposure to dust and debris, and provided
      information about mental health resources.

PMID- 12238536
TI  - Syndromic surveillance for bioterrorism following the attacks on the World Trade
      Center--New York City, 2001.
AB  - Immediately after the September 11, 2001, terrorist attacks on the World Trade
      Center (WTC), the New York City Department of Health and Mental Hygiene
      (NYCDOHMH) was concerned about the possibility of a secondary attack with a
      biologic agent. Because NYCDOHMH lost communications as a result of the attacks,
      concern arose that this disruption would affect the ability to recognize a
      bioterrorist event. To address this concern, NYCDOHMH quickly implemented a
      syndromic surveillance system in hospital emergency departments (EDs) to identify
      a large-scale bioterrorist event and other health conditions related to the WTC
      attacks. This report describes the operational and maintenance aspects of
      conducting syndromic surveillance for bioterrorism (BT) and demonstrates the
      limitations of drop-in systems that rely on manual data collection. Health
      departments that are establishing early warning systems for BT should consider
      seeking routinely collected electronic data.

PMID- 12238537
TI  - Deaths in World Trade Center terrorist attacks--New York City, 2001.
AB  - On September 11, 2001, terrorists flew two hijacked airplanes into the World
      Trade Center (WTC) in lower Manhattan in New York City (NYC), destroying both
      towers of the WTC. This report presents preliminary vital statistics on the
      deaths caused by the terrorist attacks and describes the procedures developed by
      the New York City Department of Health and Mental Hygiene (NYCDOHMH) to issue
      death certificates in response to the attacks. These data underscore the need for
      legal mechanisms to expedite the issuance of death certificates in the absence of
      human remains and the need for vital registration systems that can be relocated
      in case of emergency.

PMID- 12238538
TI  - New classification for deaths and injuries involving terrorism.
AB  - Classification of the deaths and injuries that occurred as the result of the
      events of September 11, 2001, presented CDC's National Center for Health
      Statistics (NCHS) with a dilemma. Under the current classification systems for
      mortality and morbidity, the World Health Organization's International
      Classification of Diseases, Tenth Revision (ICD-10) and the United States'
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9-CM), deaths and injuries associated with acts of terrorism could not be
      identified uniquely.

PMID- 12238539
TI  - Use of respiratory protection among responders at the World Trade Center site-
      New York City, September 2001.
AB  - The terrorist attacks on the World Trade Center (WTC) on September 11,2001,
      created an occupational health and safety challenge for New York City (NYC)
      firefighters and rescue workers responding to the disaster. Immediate respiratory
      hazards included explosions, fire, falling debris, and dust clouds containing
      particulate matter comprised of pulverized building materials. Ongoing risks
      included lingering particulate matter in the air and intermittent combustion
      products from initial and persistent fires beneath the rubble pile. Because the
      nature and extent of exposures in disaster situations are complex and difficult
      to characterize, the use of adequate personal protective equipment (PPE),
      including respiratory protection, is essential in protecting the health of
      firefighters and other rescue workers. During the weeks after September 11, the
      NYC Fire Department's Bureau of Health Services (FDNY-BHS) and CDC's National
      Institute for Occupational Safety and Health (NIOSH) organized a collaborative
      study to evaluate occupational hazards and exposures for these workers, including
      their use of respiratory protection. This report summarizes the results of that
      study, which indicate that the majority of firefighters did not use adequate
      respiratory protection during the first week of the rescue/recovery operation.

PMID- 12238540
TI  - Impact of September 11 attacks on workers in the vicinity of the World Trade
      Center--New York City.
AB  - In January 2002, CDC's National Institute for Occupational Safety and Health
      received requests for Health Hazard Evaluations from labor unions representing
      workers employed in buildings in the vicinity of the World Trade Center (WTC).
      Workers reported persistent physical and mental health symptoms that they
      associated with exposures from the WTC collapse and ensuing fires. To address
      these concerns, CDC conducted surveys of workers at four workplaces in New York
      City (NYC), a high school (high school A) and college (college A) near the WTC
      site, and a high school (comparison high school B) and college (comparison
      college B) > or = 5 miles from the WTC site to determine rates of physical and
      mental health symptoms. This report summarizes the preliminary results of the
      employee surveys, which indicated that workers employed near the WTC site had
      significantly higher rates of physical and mental health symptoms than workers
      employed > or = 5 miles from the site. Intervention programs should be tailored
      to address the needs of these workers, and the effectiveness of these programs
      should be evaluated. Further assessment is warranted to describe the nature and
      extent of illness in specific working groups and individual medical follow-up in
      those with persistent symptoms.

PMID- 12238542
TI  - Can a state-of-the-art D-dimer test be used to determine the need for CT imaging
      in patients suspected of having pulmonary embolism?
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to determine whether a
      simple rapid blood test can obviate computed tomography (CT) in a sizable
      percentage of patients suspected of having pulmonary embolism, based on the
      hypothesis that negative D-dimer results could eliminate any further search for
      pulmonary embolism. MATERIALS AND METHODS: At the authors' institution, 2,121
      sequential patients underwent a whole-blood antibody agglutination test for cross
      linked fibrin degradation products (D-dimer). Of these patients, 844 had positive
      test results and were not further considered. A retrospective review included
      reports of all multisection combined CT venographic and pulmonary angiographic
      studies obtained within 48 hours of the D-dimer assay for the 1,277 patients with
      negative D-dimer results; 229 (18%) of these 1,277 patients underwent combined CT
      venography and pulmonary angiography, usually within 24 hours. RESULTS:
      Retrospective review of the imaging examinations that were discrepant with the D
      dimer results revealed only three false-negative D-dimer results. Of the 229
      patients in whom combined CT venography and pulmonary angiography was performed
      for suspected pulmonary embolism, 226 (98.7%) had no evidence of acute pulmonary
      embolism or deep venous thrombosis. The negative predictive value of a negative D
      dimer result was therefore 98.7% (confidence interval, 96.2%-99.7%). CONCLUSION:
      The D-dimer assay is a simple rapid blood test that is sensitive to the presence
      of acute thrombosis. Very few patients with negative results have acute deep
      venous thrombosis or pulmonary embolism, with combined CT venography and
      pulmonary angiography used as the reference standard.

PMID- 12238541
TI  - The perception of breast cancer: what differentiates missed from reported cancers
      in mammography?
AB  - RATIONALE AND OBJECTIVES: Mammographers map endogenous and exogenous factors into
      decisions whether to report the presence of a malignant finding in a mammogram
      case. Thus, to understand how image-based elements are translated into observer
      based decisions, the authors used spatial frequency analysis to model the areas
      on mammograms that attracted visual attention, in addition to the areas localized
      as abnormal. MATERIALS AND METHODS: Four mammographers read 40 two-view mammogram
      cases, of which 30 contained at least one malignant lesion visible on one or two
      views. Their eye positions were recorded during visual search. Once the
      mammographer felt confident enough to provide an initial impression of the case
      ("normal" or "abnormal"), the eye position monitoring was turned off and the
      mammographer indicated, with a mouse-controlled cursor, the location and nature
      of any malignant findings. Regions that elicited an overt or a covert response by
      the mammographers were extracted for processing by means of wavelet packets and
      artificial neural networks. RESULTS: Different decision outcomes yielded
      different energy representations, in the spatial frequency domain. These energy
      representations were used by an artificial neural network to predict decision
      outcome in areas of interest, derived from eye position analysis, on mammograms
      from new cases. Individual trends were observed for each mammographer.
      CONCLUSION: Spatial frequency representation of regions that attracted a given
      mammographer's visual attention may be useful for characterizing how that
      mammographer will respond to the visually selected areas.

PMID- 12238543
TI  - Effect of emergency department CT on neuroimaging case volume and positive scan
      rates.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to determine the
      effect a computed tomographic (CT) scanner in the emergency department (ED) has
      on neuroimaging case volume and positive scan rates. MATERIALS AND METHODS: The
      total numbers of ED visits and neuroradiology CT scans requested from the ED were
      recorded for 1998 and 2000, the years before and after the installation of a CT
      unit in the ED. For each examination type (brain, face, cervical spine), studies
      were graded for major findings (those that affected patient care), minor
      findings, and normal findings. The CT utilization rates and positive study rates
      were compared for each type of study performed for both years. RESULTS: There was
      a statistically significant increase in the utilization rate after installation
      of the CT unit (P < .001). The fractions of studies with major findings, minor
      findings, and normal findings changed significantly after installation of the CT
      unit for facial examinations (P = .002) but not for brain (P = .12) or cervical
      spine (P = .24) examinations. In all types of studies, the percentage of normal
      examinations increased. In toto, there was a significant decrease in the positive
      scan rate after installation of the CT scanner (P = .004). CONCLUSION: After
      installation of a CT scanner in the ED, there was increased utilization and a
      decreased rate of positive neuroradiologic examinations, the latter primarily due
      to lower positive rates for facial CT scans.

PMID- 12238544
TI  - Natural display mode for digital DICOM-conformant diagnostic imaging.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to investigate the
      verification of the contrast display properties defined by the digital imaging
      and communication in medicine (DICOM) PS (picture archiving and communication
      system [PACS] standard) 3.14-2001 gray-scale display function standard and their
      dependency on display luminance range and video signal bandwidth. MATERIALS AND
      METHODS: Contrast sensitivity and contrast linearity of DICOM-conformant displays
      were measured in just-noticeable differences (JNDs) on special perceptual
      contrast test patterns. Measurements were obtained six times at various display
      settings under dark room conditions. RESULTS: Display luminance range and video
      bandwidth had a significant effect on contrast perception. The perceptual
      promises of the standard could be established only with displays that were
      calibrated to a unity contrast resolution, at which the number of displayed
      intensity steps was equal to the number of perceivable contrast steps (JNDs).
      Such display conditions provide for visual perception information at the level of
      single-step contrast sensitivity and full-range contrast linearity. These
      "natural display" conditions also help minimize the Mach banding effects that
      otherwise reduce contrast sensitivity and contrast linearity. CONCLUSION: Most,
      if not all, conventionally used digital display modalities are driven with a
      contrast resolution larger than 1. Such conditions reduce contrast perception
      when compared with natural imaging conditions. The DICOM-conformant display
      conditions at unity contrast resolution were characterized as the "natural
      display" mode, and, thus, the authors a priori recommend them as being useful for
      making a primary diagnosis with PACS and teleradiology and as a standard for
      psychophysical research and performance measurements.

PMID- 12238545
TI  - Independent versus sequential reading in ROC studies of computer-assist
      modalities: analysis of components of variance.
AB  - RATIONALE AND OBJECTIVES: The authors analyzed two methods for arranging the
      temporal sequencing of unaided versus computer-assisted reading in multiple
      reader, multiple-case receiver operating characteristic studies of detection of
      solitary pulmonary nodules on chest radiographs. In the "independent" mode the
      readings are separated by about I month; in the "sequential" mode, the computer
      assisted reading immediately follows the unassisted reading. MATERIALS AND
      METHODS: The authors used the method of Beiden, Wagner, and Campbell (BWC) to
      decompose the components of variance of receiver operating characteristic
      accuracy measures into those that are correlated and those that are uncorrelated
      across reading conditions. Only the latter contribute to uncertainty in estimates
      of the difference in accuracy measures across reading conditions (unaided vs
      aided). This method was used to analyze data from two independent studies of the
      detection of solitary pulmonary nodules on chest radiographs. RESULTS: In the
      sequential reading mode the components that were correlated across reading
      conditions increased compared to the independent reading mode, as might be
      expected. What was not anticipated was the fact that the total reader variance
      was approximately the same for the two reading modes. The results were remarkably
      similar across the two independent studies analyzed. CONCLUSION: The sequential
      reading mode may thus be the more sensitive probe of the difference between
      unassisted and computer-assisted reading, if the mean effect is unperturbed (as
      here). It is also the least demanding on the logistics and investment of reader
      time.

PMID- 12238546
TI  - Counterpoint to analysis of ROC studies of computer-assisted modalities.

PMID- 12238547
TI  - Teaching radiology to medical students: an integrated approach.
AB  - RATIONALE AND OBJECTIVES: This study assessed medical student satisfaction with
      radiology lectures integrated into the 3rd-year student internal medicine
      clerkship, compared with faculty lectures in an independent radiology course, and
      investigated the effects of integrated instruction on departmental compensation
      from the medical school. MATERIALS AND METHODS: Students' evaluations were
      compared, with two-way analysis of variance, for faculty who presented lectures
      in an integrated radiology course and faculty who presented lectures in an
      independent radiology course from July 1998 to June 2001. Radiology department
      compensation from the medical school for each course was computed per contact
      hour. RESULTS: For the integrated course (663 evaluations), the mean overall
      faculty rating was 1.44 (1 = excellent, 5 = poor), lower (more positive) than the
      mean overall rating of 1.53 for the independent course (518 evaluations) (P =
      .037). The interaction between type of instruction and topic was significant only
      for chest and musculoskeletal imaging, which were rated more positive and less
      positive in the integrated course, respectively (P < .001). For the integrated
      course the radiology department received $762 per lecture hour, and for the
      independent course it received $296 per contact hour (all types) and $1,183 per
      lecture hour. CONCLUSION: Student ratings of faculty lectures in an integrated
      course were excellent and comparable to those in an independent radiology course.
      The medical school differentiated the efforts of radiology faculty in the two
      courses through its budgeting process, awarding greater compensation per contact
      hour for participation in the integrated course. If only lecture hours are
      considered, compensation was greater for the independent course.

PMID- 12238548
TI  - The General Electric-Association of University Radiologists Radiology Research
      Academic Fellowship: ten-year review, current status, and vision for the future.

PMID- 12238549
TI  - Radiology report quality: a cohort study of point-and-click structured reporting
      versus conventional dictation.

PMID- 12238550
TI  - Functional MR imaging to evaluate sensory processing in dyslexia.

PMID- 12238551
TI  - MR imaging in the prenatal diagnosis of fetal chest masses: effects on diagnostic
      accuracy, clinical decision making, parental understanding, and prediction of
      neonatal respiratory health outcomes.

PMID- 12238552
TI  - The spoken word.

PMID- 12238553
TI  - Report on the NIBIB update and opportunities symposium.

PMID- 12238554
TI  - Biomedical imaging in the postgenomic era: opportunities and challenges.

PMID- 12238555
TI  - The training gap: an acute crisis in behavioral health education.
AB  - Changes in health care have outpaced changes in the educational programs offered
      to the behavioral health workforce. The result is a training gap that leaves
      graduate students, working professionals, and other direct care providers
      inadequately prepared for practice in the current health care environment. This
      article is based on a keynote address delivered at the Annapolis Conference on
      Behavioral Health Workforce Education and Training. Major changes in health care
      are reviewed, followed by a description of the training gap as an acute crisis
      that impedes the delivery of effective and efficient mental health and addiction
      services. The author describes a national initiative to narrow the training gap
      and he calls for collective action by the varied groups and organizations that
      have a stake in this agenda.

PMID- 12238556
TI  - Sometimes a great notion ... a common agenda for change.
AB  - In the midst of a sea of change in the behavioral health care field, there is
      emerging a common agenda regarding critical issues and challenges. This article
      briefly examines the implications for education and training as we pursue this
      common agenda. Understanding the process of social change helps to chart a course
      for addressing the identified challenges.

PMID- 12238557
TI  - Educational best practices.
AB  - There are few reports from the behavioral health field that focus on educational
      best practices. This article summarizes a panel presentation from the Annapolis
      Conference in which four different programs were described: (1) a provider
      educational initiative, (2) a tool-kit project related to evidence-based
      services, (3) a multidisciplinary faculty training program in addictions, and (4)
      an AIDS education project. While such innovative educational practices appear to
      be the exception rather than the norm, they do offer ideas and strategies for
      challenging and energizing current educational practices in behavioral health.

PMID- 12238558
TI  - Graduate education and training for contemporary behavioral health practice.
AB  - Over the past decade, a new paradigm in behavioral health care has emerged. It
      places emphasis on cost control, evidence-based practice, patient safety, access
      to care, treatment relevance for diverse populations, consumerism, and quality of
      care. Unfortunately, graduate education and training programs have had difficulty
      keeping pace with the dramatic changes in the field. As a consequence, there is
      concern that the graduates of many of these programs are not being adequately
      prepared to practice in current health care systems. This article reviews the
      nature of recent changes in behavioral health care, the current status of
      graduate education programs with respect to these changes, and offers 15
      recommendations for increasing the relevance of graduate education to
      contemporary clinical practice.

PMID- 12238559
TI  - Current issues in continuing education for contemporary behavioral health
      practice.
AB  - The evolving health care system poses a number of challenges for the continuing
      development of the professional workforce. An overview of continuing education is
      provided, including typical objectives, format, content, and sponsors. Data are
      presented on continuing education requirements by discipline and by state. The
      forces of change that have driven the need for revised approaches to continued
      professional development are described, including research findings on the
      apparent lack of effectiveness of didactic learning activities. Current issues in
      continuing education are discussed, with a focus on educational content,
      financing, and the use of emerging technologies as a medium for these activities.
      The authors conclude with five recommendations for improving the process and
      content of continuing education for the professional behavioral health workforce.

PMID- 12238560
TI  - Training and education needs of consumers, families, and front-line staff in
      behavioral health practice.
AB  - Much of the behavioral health care delivered to people with serious mental
      illnesses and chronic addictive disorders is provided by front-line or direct
      service mental health workers. Issues related to the qualifications, training,
      and ongoing evaluation of the competencies of this important provider group have
      received scant attention in the behavioral health field. This paper explores the
      educational needs and best practices of the consumers and families who carry much
      of the burden of caring for disabled populations, as well as the front-line
      staff, many of whom are employed in state psychiatric hospitals and community
      mental health or addiction treatment systems. Within the overall context of
      culturally competent behavioral health care, specific recommendations are
      proposed in an attempt to move the field forward.

PMID- 12238561
TI  - Problems in behavioral health care: leap-frogging the status quo.
AB  - A version of this paper was presented as a keynote address entitled "Strategies
      for Catalyzing Change" at the September 2001 Annapolis Conference on Behavioral
      Health Workforce Education and Training. It explores some of the problems
      inherent in our present health care system and suggests that ultimately,
      revamping pre-professional training is the key to sustained system change. While
      the paper approaches the problems inherent in our behavioral health care system
      from a psychiatric perspective, it is believed that similar issues and concerns
      exist across disciplines and that ultimately the solution requires our ability to
      transcend narrower perspectives.

PMID- 12238562
TI  - Student voices: perspectives on behavioral health education.
AB  - The Annapolis Conference on Behavioral Health Workforce Education and Training
      was convened in September 2001 to address the relevance and quality of efforts to
      educate those who provide mental health and addiction services. It was essential
      that students, as the consumers of educational programs, be represented in the
      dialogue. Four students and one recent graduate joined a diverse group in
      Annapolis, which included professionals, administrators, educators, consumers of
      behavioral health services, and family members. The students who attended were
      drawn from the professions of psychiatry, psychology, social work, and nursing.
      In a series of personal narratives, these individuals present their views on the
      conference, on education and training, and on the behavioral health field in
      general.

PMID- 12238563
TI  - Signalling mechanisms involved in the induction of inducible nitric oxide
      synthase by Lactobacillus rhamnosus GG, endotoxin, and lipoteichoic acid.
AB  - BACKGROUND AND AIMS: Probiotic Lactobacillus rhamnosus GG (Lactobacillus GG) has
      been found beneficial in the treatment of viral and antibiotic-associated
      diarrhea. Recently, it has also been shown to induce nitric oxide (NO)
      production, and have some other immunostimulatory effects. The aim of the present
      study was to investigate the mechanisms involved in the induction of inducible
      nitric oxide synthase (iNOS) and NO production by Lactobacillus GG. METHODS AND
      RESULTS: iNOS expression and NO production induced by Lactobacillus GG,
      lipopolysaccharide (LPS), and lipoteichoic acid (LTA) was abrogated by NOS
      inhibitors L-NMMA and 1400W, by a protein synthesis inhibitor cycloheximide, by a
      tyrosine kinase inhibitor genistein and by a NF-kappaB inhibitor
      pyrrolidinedithiocarbamate (PDTC) in J774 macrophages. Polymyxin B inhibited NO
      production induced by LPS, but did not inhibit Lactobacillus GG induced NO
      production. p42/44 MAP-kinase inhibitor PD98059, dexamethasone and cyclosporine A
      inhibited partially iNOS protein expression and NO formation in Lactobacillus GG,
      LPS and LTA treated cells. Ro 31-8220 (protein kinase C inhibitor) and SB203580
      (p38 MAP-kinase inhibitor) had only a minor effect on NO production. CONCLUSIONS:
      Lactobacillus GG induced NO production through iNOS pathway and the mechanisms
      mediating that process were very similar with those involved in LPS and LTA
      induced NO synthesis.

PMID- 12238564
TI  - Dexamethasone inhibits apoptosis of human neutrophils induced by reactive oxygen
      species.
AB  - Neutrophils are completely differentiated cells that die in tissues a few days
      after they migrate from the vascular compartment as a consequence of a rigouous
      apoptotic program. Many of the mediators produced during an inflammatory response
      delay neutrophil apoptosis allowing a more efficient removal of microorganisms
      but also favoring the tissue damage by reactive oxygen species (ROS) and
      lysosomal proteins released by neutrophils. Glucocorticoids delay the apoptosis
      of neutrophils but the mechanisms are not completely understood. To investigate
      the inhibition of glucocorticoids on neutrophil apoptosis we have used the
      glucose/glucose oxidase (G/GO) system as a constant source of hydrogen peroxide.
      When neutrophils are incubated in the presence of the G/GO system, a significant
      acceleration of their apoptotic response is observed. Preincubation with 10(-6)
      M, 10(-7) M, 10(-8) M or 10(-9) M of dexamethasone, negatively modulated the
      spontaneous and G/GO induced apoptosis of neutrophils. Then the G/GO system is a
      useful model to simulate the oxidative stress of neutrophils, and that the effect
      of DXM on neutrophil apoptosis depends, at least in part, on blocking the
      proapoptotic effect of ROS.

PMID- 12238565
TI  - Endomorphin-2 modulates productions of TNF-alpha, IL-1beta, IL-10, and IL-12, and
      alters functions related to innate immune of macrophages.
AB  - We evaluate immunological effects of opioid peptide endomorphin-2 on the
      production of cytokines related to inflammation and Th1/Th2 balance, and
      functions related to innate immune of rat peritoneal macrophages. Endomorphin-2
      inhibited TNF-alpha, IL-10, and IL-12 productions, but potentiated IL-1beta
      production by macrophages. Moreover, endomorphin-2 potentiated macrophage
      adhesion to fibronectin, and the expression of adhesion molecule Mac-1 on
      macrophages. In contrast, endomorphin-2 suppressed phagocytosis of opsonized E.
      coli by macrophages, without affecting phagocytosis of non-opsonized E. coli. In
      addition, endomorphin-2 inhibited macrophage chemotaxis, and the production of
      superoxide anion by macrophages. These results suggest that endomorphin-2 may
      alter macrophage functions such as cytokine productions and functions related to
      innate immune.

PMID- 12238566
TI  - A green tea-derived polyphenol, epigallocatechin-3-gallate, inhibits IkappaB
      kinase activation and IL-8 gene expression in respiratory epithelium.
AB  - Interleukin-8 (IL-8) is a principle neutrophil chemoattractant and activator in
      humans. There is interest in developing novel pharmacological inhibitors of IL-8
      gene expression as a means for modulating inflammation in disease states such as
      acute lung injury. Herein we determined the effects of epigallocatechin-3-gallate
      (EGCG), a green tea-derived polyphenol, on tumor necrosis factor-alpha (TNF
      alpha)-mediated expression of the IL-8 gene in A549 cells. EGCG inhibited TNF
      alpha-mediated IL-8 gene expression in a dose response manner, as measured by
      ELISA and Northern blot analysis. This effect appears to primarily involve
      inhibition of IL-8 transcription because EGCG inhibited TNF-alpha-mediated
      activation of the IL-8 promoter in cells transiently transfected with an IL-8
      promoter-luciferase reporter plasmid. In addition, EGCG inhibited TNF-alpha
      mediated activation of IkappaB kinase and subsequent activation of the IkappaB
      alpha/NF-kappaB pathway. We conclude that EGCG is a potent inhibitor of IL-8 gene
      expression in vitro. The proximal mechanism of this effect involves, in part,
      inhibition of IkappaB kinase activation.

PMID- 12238567
TI  - Endotoxin protection from oxygen toxicity: effect on pulmonary neutrophils and L
      selectin.
AB  - The mechanisms by which sublethal doses of endotoxin protect against hyperoxic
      lung injury are not completely understood. We hypothesized that endotoxin
      treatment would result in a decreased inflammatory response to hyperoxia and that
      this would be accompanied by activation of neutrophils (as evidenced by loss of L
      selectin) in the peripheral circulation. Adult rats were injected with endotoxin
      0.5 mg/kg prior to and 24 hr after onset of exposure to > or = 98% O2. After 56
      hr of hyperoxia, pulmonary neutrophils were lower in the O2/endotoxin group
      compared to O2 controls as measured by myeloperoxidase in lung homogenates and
      neutrophil counts in bronchoalveolar lavage fluid. Circulating neutrophils were
      also significantly lower in the O2/endotoxin group compared to O2 controls at 56
      hr. Expression of the neutrophil adhesion molecule, L-selectin, was lower at 4
      and 24 hr in the endotoxin-treated rats compared to O2 controls. There were no
      differences at 48 hr. Expression of CD18 rose significantly in the O2/endotoxin
      group after 4 hr, but thereafter did not differ from O2 controls. In summary,
      endotoxin protection from O2 toxicity was associated with reduced neutrophils in
      the lung and a loss of L-selectin from peripheral blood neutrophils.

PMID- 12238568
TI  - Prevalence of penicillin non-susceptible invasive pneumococcal disease in the
      elderly in Scotland, 1992-99.
AB  - Penicillin resistance of Pneumococci is a problem in several European countries.
      Therefore, we examined 510 invasive pneumococcal isolates, collected between 1992
      and 1999 via a national network of diagnostic laboratories covering the entire
      population of Scotland, for penicillin susceptibility, in order to determine the
      prevalence, site of infection and serogroup/type distribution of penicillin
      resistant Pneumococci in the elderly (> or = 65 y). Of the 510 isolates, 91.6% (n
      = 467) were from blood, 4.7% (n = 24) from other sterile sites and 3.7% (n = 19)
      from cerebrospinal fluid. The prevalence of penicillin non-susceptible isolates
      during the study period was 9%. An increase in the proportion of Pneumococci non
      susceptible to penicillin was detected from 1996 onwards, from 10.8% in 1996 to
      14.3% in 1999. There were 2 isolates with high-level penicillin resistance, both
      of which were of serotype 14, accounting for 4.3% (2/46) of all non-susceptible
      isolates. Penicillin non-susceptible isolates belonged to the following
      serogroups: 14 (32.6%); 9 (30.4%); 6 (19.6%); 23 (10.9%); and 19 (6.5%). The
      leading non-susceptible serotype/group varied according to the specimen type:
      serotype 14 for blood and serogroup 9 for all other sterile sites. Current
      polysaccharide and new 7-, 9- and 11-valent conjugate vaccine formulations
      included the serogroups responsible for all the penicillin non-susceptible
      isolates detected. Therefore vaccination represents the most effective strategy
      for decreasing the burden of drug resistance. Constant surveillance of the
      patterns of antibiotic non-susceptible isolates, the site of infection and the
      serogroup/type are necessary in order to select antibiotic therapy and establish
      vaccination policy for the prevention of invasive pneumococcal disease.

PMID- 12238569
TI  - Antimicrobial susceptibility of Bacillus anthracis in an endemic area.
AB  - We aimed to test the antimicrobial susceptibility of 28 Bacillus anthracis
      strains isolated from cutaneous anthrax cases to various antimicrobial agents
      using the Sceptor automatic system in an anthrax endemic area. All strains tested
      were susceptible to penicillin (MIC < or = 0.03 microg/ml). Piperacillin
      tazobactam and carbapenems showed good activity towards all strains. Trimethoprim
      sulfamethoxazole and cefepime had no activity. Strains were also tested with
      other antimicrobials.

PMID- 12238571
TI  - Prevalence of tuberculosis infection and comparison of multiple-puncture liquid
      tuberculin test and Mantoux test among drug users.
AB  - In order to determine the prevalence of latent infection due to Mycobacterium
      tuberculosis in drug users and to provide centres for drug users with a practical
      tool for tuberculosis screening, 237 drug users were subjected to the Monotest
      and, for reference purposes, to the Mantoux test. The overall prevalence of
      subjects with a tuberculin skin reaction size > or = 5 mm in the Mantoux test was
      25.7%; utilizing a cut-off of > or = 10 mm, the prevalence was 11.4%.
      Irrespective of cut-off, the Monotest showed a sensitivity of > 90% and a
      specificity of > 80%. At a prevalence of 25.7%, and with cut-offs of > or = 5 or
      > or = 10 mm, the positive predictive value was 83% or 62.2%, respectively.
      Irrespective of cut-off, the negative predictive value was > 97%. In conclusion,
      the Monotest proved satisfactory as a tool for epidemiological screening in a
      population with a high prevalence for latent tuberculosis, namely drug users.

PMID- 12238570
TI  - Bacteremia caused by Escherichia coli producing extended-spectrum beta-lactamase:
      a case-control study of risk factors and outcomes.
AB  - A case-control study was conducted in order to identify the risk factors
      associated with bloodstream infection caused by Escherichia coli producing
      extended-spectrum beta-lactamase (ESBL) and to determine the outcomes of infected
      patients. Risk factors associated with ESBL production, according to univariate
      analysis, included a history of recent hospitalization [odds ratio (OR) 4.3, 95%
      confidence interval (CI) 2.1-8.9; p < 0.001], severe underlying diseases (OR 15,
      95% CI 4.4-51.5; p < 0.001), prior exposure to urinary catheters (OR 8.3, 95% CI
      3.2-21.7; p < 0.001) and nosocomial (OR 14.1, 95% CI 6.1-32.8; p < 0.001) or
      urinary (OR 3.6, 95% CI 1.7-7.4; p < 0.001) origin of the bacteria. Multivariate
      analysis revealed that severe underlying diseases (OR 31.2, 95% CI 6.7-144; p <
      0.001) and nosocomial (OR 16.5, 95% CI 5.6-49; p < 0.001) and urinary origins (OR
      7.8, 95% CI 2.6-23.8; p < 0.001) of the bacteria were independently associated
      with ESBL production in bacteremic E. coli. Crude mortality in case patients was
      more than twice as high as that in controls (p = 0.04). Production of ESBL
      increased the risk of inappropriate initial therapy (OR 95.6, 95% CI 27.4-334.2;
      p < 0.001). Treatment failed in 4/7 case patients treated with ceftazidime to
      which the isolate was susceptible in vitro. Our findings have implications for
      the choice of empirical therapy in nosocomial urinary tract infection.

PMID- 12238572
TI  - Effect of age on antibody titer to Mycoplasma pneumoniae.
AB  - Between January 1996 and September 1999, 13,650 serum samples from 12,337
      patients were examined for antibodies to Mycoplasma pneumoniae at the Institute
      of Hygiene, University Hospital Vienna in the course of routine diagnosis.
      Antibody determination was performed by means of the microparticle agglutination
      assay Serodia Myco II. Overall, positive results (antibody titer > or = 1:40)
      were obtained in 2028 patients (16.4%). Age details were available for analysis
      in 2016 positive patients. Young children (< or = 9 y) who tested positive showed
      a geometric mean titer of 1:137.9 (95% confidence interval: 117.7-161.4). The
      geometric mean titers of positive patients decreased significantly with age
      (Spearman's correlation coefficient -0.20; p < 0.0001). Only 1/87 patients with
      serological evidence of M. pneumoniae infection aged > or = 70 y showed a titer
      of > or = 1:320. These data highlight the fact that, in the elderly, acute M.
      pneumoniae infection has to be considered in cases with slightly elevated
      antibody titers, which are usually referred to as borderline in children and
      young adults.

PMID- 12238573
TI  - Nosocomial transmission of HCV in a cardiology ward during the window phase of
      infection: an epidemiological and molecular investigation.
AB  - Nosocomial spread of HCV and other blood-borne pathogens continues to occur in
      the Western world despite the screening of blood products. Using molecular and
      epidemiological methods we investigated an outbreak of HCV involving 3 patients
      following percutaneous coronary intervention at a Swedish hospital. The most
      likely mode of transmission was contamination of a multidose vial of saline used
      for the flushing of intravenous catheters. It may, therefore, be prudent to
      restrict the use of such vials, in addition to promoting vigorous adherence to
      standard hygiene procedures in order to prevent the recurrence of similar
      outbreaks in the future.

PMID- 12238574
TI  - Diagnosis of onchocerciasis using highly specific and sensitive native proteins.
AB  - We describe a highly immunogenic low molecular weight fraction of proteins
      obtained from Onchocerca volvulus. It is comprised of a mixture of native
      proteins ranging in molecular weight from 10 to 40 kDa and is collectively
      designated PakF. Unlike other Onchocerca (and other filarial) antigens previously
      described, IgG4 antibody responses to this protein mixture were absent or low. In
      a simple, IgG-based dot blot assay, this mixture of native proteins showed high
      sensitivity, comparable to or better than that of other previously described
      recombinant proteins, when used to detect infected individuals in endemic areas
      of Ghana and Guatemala. The specificity was also high when evaluated using sera
      from patients with other filarial infections. Arguments are put forward to
      suggest that such a native fraction could present an interesting alternative to
      the use of well-defined molecules, which are expensive, labile or prone to
      denaturation, in endemic areas.

PMID- 12238575
TI  - Diagnostic use of 3 techniques for identification of microsporidian spores among
      AIDS patients in Portugal.
AB  - The calcofluor stain (CF), the monoclonal antibody (MAb) 3B6 indirect
      immunofluorescence assay (IFA) and the modified trichrome blue stain (MT) were
      compared in terms of their reproducibility in a routine laboratory and in order
      to evaluate the percentage of cases of microsporidiosis in Portuguese HIV
      patients. A total of 166 faeces samples, 71 pulmonary specimens and 43 urine
      samples were studied using the 3 techniques. CF had a high sensitivity and a
      moderate specificity when applied to faeces samples. The sensitivity was lower
      with pulmonary specimens. The method is easy and quick to perform but readings
      take a long time to obtain. The MAb 3B6 IFA had a good to excellent sensitivity
      when applied to faeces and urine samples, but moderate sensitivity in pulmonary
      specimens. Readings were quick and easy to obtain, but the assay took longer to
      perform than the other 2 techniques. There was a greater correlation between the
      results obtained with the MT and MAb 3B6 IFA techniques than between those
      obtained with the MT and CF techniques. In conclusion, the MT performed better
      than the MAb 3B6 IFA and CF and continues to have an important place in a routine
      laboratory for the diagnosis of microsporidiosis. This work also confirms the
      existence of a relatively high proportion (30%) of cases of infection with
      Microsporidia, especially intestinal microsporidiosis, in HIV patients in
      Portugal.

PMID- 12238576
TI  - Risk factors for recurrence of Clostridium difficile-associated diarrhea in the
      elderly.
AB  - Risk factors that influence the recurrence of nosocomial Clostridium difficile
      associated diarrhea (CDAD) were determined in an 18-month follow-up study in a
      subacute geriatric department. A case-control study was conducted, comparing 43
      patients with recurrent C. difficile-associated diarrhea (RCDAD) (case patients)
      with 38 patients who had only 1 episode of CDAD (control patients). The mean age
      of patients was 81.6 +/- 7.2 y (range 64-95 y). All cases with CDAD were
      receiving antibiotic therapy. RCDAD occurred in 53.1% of patients. Risk factors
      for RCDAD included fecal incontinence (p < or = 0.04), longer duration of fever
      from admission until first episode of CDAD (p < or = 0.02) and H2-antagonist
      treatment (p < or = 0.02). This study shows that RCDAD is a common clinical event
      in elderly hospitalized patients and may be predictable in some groups of
      patients.

PMID- 12238577
TI  - Neonatal bacteraemia: a population-based study.
AB  - The aims of this study were to explore the incidence of neonatal bacteraemia and
      identify the risk factors among neonatal intensive care unit (NICU) patients. The
      study included 3339 neonates admitted to the NICU of Ioannina University
      Hospital, North-Western Greece, during the 10-y period 1989-98. Logistic
      regression was used to assess the contribution of different risk factors to
      bacteraemia. A diagnosis of bacteraemia was made in 90 neonates (2.7%), 10 of
      whom (11%) died. Gram-negative bacilli, coagulase-negative Staphylococci and
      Streptococci were the most common pathogens: 42%, 34% and 17%, respectively.
      Premature rupture of membranes was the main risk factor for early-onset sepsis
      (relative risk 6.28) and respiratory distress syndrome was the main risk factor
      for late-onset sepsis (relative risk 5.70). The relative size of neonates for
      their gestational age did not appear to influence the risk of infection. Case
      fatality was higher for early- than for late-onset sepsis (relative risk 6.59).
      In conclusion, certain conditions were confirmed to predispose patients to
      neonatal bacteraemia; neonatal morbidity and mortality can be reduced by
      intervening to control these predisposing factors.

PMID- 12238578
TI  - Differences in antibiotic prescribing patterns between general practitioners in
      Scandinavia: a questionnaire study.
AB  - There has been a dramatic increase in the prevalence of antibiotic-resistant
      bacteria worldwide. In the Scandinavian countries at least 90% of total
      antibiotic use relates to outpatients and therefore it has become increasingly
      important to know the antibiotic prescription pattern of general practitioners
      (GPs) in order to implement and monitor changes in antibiotic prescribing. The
      aim of the present study was to evaluate the prescription patterns of GPs in
      Denmark, Norway and Sweden. In order to achieve a reasonable comparison, a
      questionnaire consisting of 7 case reports concerning upper and lower respiratory
      tract infections, urinary tract infections and skin and soft tissue infections
      was sent to 1,000 GPs in the 3 countries. In general, the guidelines for the
      treatment of bacterial infections in the individual countries were followed by
      the responders. In all 3 countries, penicillin V was still the drug most
      frequently used in upper and lower respiratory tract infections. The greatest
      difference in prescribing patterns among the countries was seen in the treatment
      of urinary tract infections, recurrent pharyngeal tonsillitis, acute otitis media
      and acute exacerbation of chronic bronchitis. There were also differences in the
      dosing regimens, length of treatment and use of diagnostic techniques.

PMID- 12238579
TI  - A 2-dose regimen of a recombinant hepatitis B vaccine with the immune stimulant
      AS04 compared with the standard 3-dose regimen of Engerix-B in healthy young
      adults.
AB  - An open-label randomized study was undertaken to compare a 2-dose regimen (Months
      0 and 6) of hepatitis B surface antigen (HBsAg) vaccine formulated with a novel
      adjuvant (HBsAg/AS04) with a standard 3-dose regimen (Months 0, 1 and 6) of
      licensed recombinant HBsAg vaccine in terms of immunogenicity and reactogenicity
      when administered to healthy subjects aged between 15 and 40 y. At 1 and 6 months
      after the full vaccination course there was a 100% seroprotection rate (anti-HBs
      > or = 10 mIU/ml) with the HBsAg/AS04 vaccine, compared with a 99% response rate
      with the licensed vaccine. The corresponding geometric mean titres were
      significantly higher for the novel vaccine compared to the standard vaccine:
      15,468 and 2,745 mIU/ml at Months 7 and 12 vs. 6,274 and 1,883 mIU/ml,
      respectively. There was a higher prevalence of local symptoms with the adjuvant
      vaccine (90% of doses) than with the standard vaccine (48% of doses). However,
      these symptoms (pain, swelling and redness) were predominantly of mild-to
      moderate intensity and resolved rapidly without treatment. A 2-dose regimen of
      the new HBsAg/AS04 adjuvant vaccine therefore compared favourably to the standard
      regimen in healthy young adults. It is anticipated that the simplified
      vaccination schedule may improve compliance and reduce costs.

PMID- 12238580
TI  - Constrictive pericarditis caused by candida glabrata in an immunocompetent
      patient: case report and review of literature.
AB  - Candida pericarditis is a rare disease described mostly in patients with recent
      cardiothoracic surgery or debilitating chronic diseases and is generally
      considered to be associated with high mortality. To our knowledge, we report the
      first case of Candida pericarditis in a healthy host who had not undergone
      thoracic surgery and the first documented case and cure of pericarditis caused by
      C. glabrata. The most probable underlying factor in the development of this
      pericarditis was the abdominal surgery the patient underwent to correct a
      gastrogastric fistula, without an intraabdominal leak, which developed 10 y after
      surgical gastric stapling for weight reduction. The literature on Candida
      pericarditis is reviewed. If Candida pericarditis is diagnosed early and treated
      with a combined medical and surgical approach, the prognosis today is much more
      favorable than that previously reported.

PMID- 12238581
TI  - Comparison of procalcitonin with CRP and differential white blood cell count for
      diagnosis of culture-proven neonatal sepsis.
AB  - We analysed the utility of procalcitonin (PCT) assay, either alone or in
      combination with 2 simple blood assays, for the diagnosis of culture-proven
      neonatal septicaemia. Tests for serum PCT concentration, serum CRP concentration
      and blood immature to total neutrophil leucocyte ratio all had reasonable (58
      77%) sensitivity, reasonable (62-84%) specificity, good (94-97%) negative
      predictive value and poor (16-24%) positive predictive value for the diagnosis of
      sepsis. Algorithms combining various tests produced slight improvements in
      sensitivity or specificity. Although the PCT test appeared to be useful for the
      diagnosis of neonatal sepsis in this small study, it did not offer any
      significant advantages over traditional tests for the diagnosis of infection.

PMID- 12238582
TI  - Epileptic seizure: an atypical presentation in an adolescent boy with
      neurobrucellosis.
AB  - Brucellosis is an infectious disease with multisystemic involvement caused by the
      genus Brucella. Neurological complications, including meningitis,
      meningoencephalitis, myelitis-radiculoneuritis, brain abscess, epidural abscess
      and meningovascular syndromes, are rarely encountered. We present a patient with
      epileptic seizures and aggressive mood due to chronic neurobrucellosis of 2.5 y
      duration, which was misdiagnosed as bacterial meningitis and epilepsy. This form
      of presentation has not previously been reported in the English language
      literature. We conclude that the diagnosis of neurobrucellosis should be
      considered in patients presenting with recurrent or chronic meningitis syndromes
      with or without seizure from endemic areas for brucellosis.

PMID- 12238583
TI  - Chronic lymphadenopathies and human herpes virus type 8.
AB  - Human herpes virus type 8 (HHV-8) is predominantly associated with Kaposi's
      sarcoma. Nothing is known about its manifestation in primary infection. We report
      an HIV-negative patient with chronic polyadenitis and lymphocytosis that may have
      been related to a primary HHV-8 infection.

PMID- 12238584
TI  - A case of anthrax meningitis.
AB  - Meningeal anthrax is a very rare complication of the cutaneous, respiratory and
      gastrointestinal form of anthrax infection. Anthrax bacilli, most commonly enter
      the body via the skin, and the organism then disseminates to the central nervous
      system via the hematogenous or lymphatic routes leading to fatal bacterial
      meningitis, even with intensive antibacterial therapy.

PMID- 12238585
TI  - Bordetella bronchiseptica pleural infection in a patient with AIDS.
AB  - Bordetella bronchiseptica is an important veterinary pathogen but a rare cause of
      opportunistic respiratory tract infection in humans. We describe a case of
      pleural effusion caused by B. bronchiseptica in a patient with AIDS who was
      coinfected with Mycobacterium tuberculosis. To the best of our knowledge this is
      the first case in the medical literature in which the microorganism has been
      isolated from pleural fluid.

PMID- 12238586
TI  - Persistent ulcers on the hand of an aquarium owner.
AB  - We present a patient with skin ulcers that did not respond to a 3-week course of
      treatment with amoxicillin-clavulanic acid. As the patient maintained a fish
      aquarium, mycobacterial infection was suspected. Indeed, reassessment of
      histopathology revealed acid-fast bacilli, and mycobacterial cultures at 30
      degrees C grew Mycobacterium marinum. Eventually, surgical reconstruction of the
      tendons was needed.

PMID- 12238587
TI  - Zanamivir is an effective treatment for influenza in children undergoing therapy
      for acute lymphoblastic leukemia.
AB  - We diagnosed influenza infection in 2 children receiving maintenance treatment
      for acute lymphoblastic leukemia. Both patients received zanamivir within 1 d of
      the onset of fever and their symptoms of influenza were rapidly alleviated. We
      conclude that inhaled zanamivir seems to be an effective treatment for influenza
      infection in immunocompromised patients.

PMID- 12238588
TI  - Hepatitis A after a single dose of an inactivated hepatitis A vaccine.

PMID- 12238589
TI  - Order-parameter tensor description of HPr in a medium of oriented bicelles.
AB  - Residual dipolar couplings between 15N and 1H nuclear spins in HPr were used to
      determine the protein's orientation in a medium of bicelles, oriented by a
      magnetic field. In the case of wild-type HPr the protein's non-spherical shape
      can explain its orientation in this medium. In the case of the F48W mutant it was
      found that at least one other mechanism contributes to the observed orientation
      of the protein, to a degree that depends on the concentration of phosphate ions
      in the medium. We propose that the F48W mutant has a weak affinity towards the
      bicelle-surfaces that decreases with increasing phosphate concentrations. We used
      an order-parameter description to analyse this situation and to determine the
      axis of main order and the sign of the order parameter pertaining to this
      additional orientation mechanism.

PMID- 12238590
TI  - A comparison of methods for calculating NMR cross-relaxation rates (NOESY and
      ROESY intensities) in small peptides.
AB  - Three methods for calculating nuclear magnetic resonance cross-relaxation rates
      from molecular dynamics simulations of small flexible molecules have been
      compared in terms of their ability to reproduce relaxation data obtained
      experimentally and to produce consistent descriptions of the system. The
      importance of the accuracy of the simulation versus the amount of sampling of
      phase space has also been assessed by comparing different length simulations
      performed with different time step schemes. A nine-residue peptide from the
      protein HPr of E. coli was used as a test system. The work shows that, in this
      case, single conformations or a limited ensemble of configurations are
      insufficient to properly describe the behavior of the peptide and that different
      approaches to incorporate molecular motions lead to significant differences in
      the cross-relaxation rates calculated. The correlation between the cross
      relaxation rates calculated from simulations performed with different time step
      schemes was high and increased with increasing simulation length indicating that
      the extent of sampling is more important than the details of the atomic motion.

PMID- 12238591
TI  - Accurate measurement of residual dipolar couplings in anisotropic phase.
AB  - The determination of residual dipolar couplings (RDCs) by quantitative J
      spectroscopy methods such as Heteronuclear Single Quantum Correlation with Phase
      Encoded Coupling (HSQC-PEC) is prone to systematic errors that may be caused by
      differential attenuation during the conversion of orthogonal density operator
      components into observable terms. The attenuation may be caused by miscalibration
      of radio-frequency pulses and by relaxation effects. A simple method is presented
      that allows one to remove most of these systematic errors without losses in
      sensitivity or resolution.

PMID- 12238592
TI  - Intraresidual HNCA: an experiment for correlating only intraresidual backbone
      resonances.
AB  - Resonance overlap in 13Calpha-dimension can seriously deteriorate sequential
      assignment of proteins, especially in the case of highly alpha helical or
      partially unfolded structures. In this paper, two novel triple-resonance
      experiments, for obtaining solely intraresidual HN, N, Calpha correlations, are
      introduced. The proposed experiments are complementary to the conventional
      HN(CO)CA experiment, and can be utilized for the sequential assignment of
      15N/13C/(2H)-labeled proteins. Coherence transfer efficiency of the new
      experiment is comparable to the conventional HNCA experiment on proteins with
      sufficiently long 15N transverse relaxation time. These new coherence transfer
      schemes are also very useful building blocks for experiments gathering structural
      information, such as J-couplings, exclusively on the intraresidual alpha carbon.
      Experimental assessment is demonstrated on ubiquitin at 600 1H MHz.

PMID- 12238593
TI  - Determination of residual dipolar couplings in homonuclear MOCCA-SIAM
      experiments.
AB  - In solutions with partial molecular alignment, anisotropic magnetic interactions
      such as the chemical shift anisotropy, the electric quadrupole interaction, and
      the magnetic dipole-dipole interaction are no longer averaged out to zero in
      contrast to isotropic solutions. The resulting residual anisotropic magnetic
      interactions are increasingly used in biological NMR studies for the
      determination of 3D structures of proteins and other biomolecules. In the present
      paper we propose a new approach allowing the measurement of residual HN-H(alpha)
      dipolar couplings of non-isotope enriched proteins based on the application of
      the MOCCA-SIAM experiment. This experiment allows the measurement of homonuclear
      coupling constants with an accuracy of ca. +/- 0.2 Hz and is therefore
      particularly well suited to determine residual dipolar couplings at relatively
      low degrees of molecular orientation. The agreement between experimentally
      determined residual HN-H(alpha) couplings and calculated values is demonstrated
      for BPTI.

PMID- 12238594
TI  - Reweighted atomic densities to represent ensembles of NMR structures.
AB  - A reweighted atomic probability density is introduced as a means of representing
      ensembles of NMR structures in a simple, concise and informative manner. This
      density is shown to give a better visual representation of molecular structure
      information than an unweighted density, and should provide a useful interactive
      graphics tool during the course of iterative NMR structure refinement. The
      approach is illustrated using several examples.

PMID- 12238595
TI  - REDOR: an assessment of the efficacy of dipolar recoupling with adiabatic
      inversion pulses.
AB  - A numerical assessment of the efficacy of REDOR recoupling of heteronuclear
      dipolar interactions employing adiabatic dephasing pulses has been carried out by
      considering an isolated dipolar coupled spin 1/2 I-S system. At moderate magic
      angle spinning frequencies in the range of 3-6 kHz and when the CSA of the
      dephased spins is large, it is shown that efficient broadband heteronuclear
      dipolar recoupling and reliable distance estimates can be achieved even under
      conditions where a significant fraction of the rotor period is occupied by the
      adiabatic pulse. The efficacy of REDOR with adiabatic inversion pulses has been
      demonstrated experimentally in two model 15N-13C spin systems, (13C',15N) Aib
      (15N) Aib-NH2 (Aib = alpha-aminoisobutyric acid) and (1-13C,15N) glycine.

PMID- 12238596
TI  - Using pisa pies to resolve ambiguities in angular constraints from PISEMA spectra
      of aligned proteins.
AB  - The structures of proteins are mapped onto the patterns of resonances in NMR
      spectra of aligned samples. This is most clearly illustrated with Pisa wheels of
      helical membrane proteins, where the distinctive 'wheel-like' patterns of
      resonances reflect the tilt and rotation of the helices in the bilayers. These
      patterns contain both structural and assignment information. This Communication
      describes a simple way of using this information to resolve angular ambiguities
      inherent in orientational constraints derived from NMR data. This contributes to
      the use of solid-state NMR of aligned samples for protein structure
      determination.

PMID- 12238597
TI  - Assignments of the 1H, 13C, and 15N resonances of the winged helix domain of the
      proto-oncoprotein cQin (FoxG1B).

PMID- 12238598
TI  - Sequence-specific resonance assignment of the carboxyl terminal domain of
      Connexin43.

PMID- 12238599
TI  - 1H, 15N and 13C chemical shift assignments of the structured core of the
      pseudomonas effector protein AvrPto.

PMID- 12238600
TI  - 1H, 15N and 13C assignments of the regulatory domains of calcium-dependent
      protein kinase (CDPK).

PMID- 12238601
TI  - 1H, 15N, and 13C resonance assignments of low molecular weight human cytoplasmic
      protein tyrosine phosphatase-A (HCPTP-A).

PMID- 12238602
TI  - 1H, 15N and 13C assignments of full length human ADP ribosylation factor 1 (ARF1)
      using triple resonance connectivities and dipolar couplings.

PMID- 12238603
TI  - Assignment of 1H, 13C and 15N resonances of human Ca2+-S100B in complex with the
      TRTK-12 peptide.

PMID- 12238604
TI  - Female sexuality and sexual dysfunction.

PMID- 12238605
TI  - Biochemical and physiological mechanisms of female genital sexual arousal.
AB  - Limited studies are available concerning physiological and biochemical mechanisms
      involved in female sexual function and dysfunction. The paucity of physiological
      and biochemical data pertaining to genital sexual arousal function is attributed,
      in part, to lack of reliable experimental models and tools for the investigation
      of female sexual arousal. This review summarizes research efforts from a number
      of laboratories in which several experimental models have been established. These
      include the development of in vivo animal models, organ bath studies, and the
      establishment of cell cultures. The availability of such experimental model
      systems have facilitated efforts aimed at defining the neurotransmitters
      responsible for vaginal smooth muscle relaxation, the role of sex steroid
      hormones and their receptors in modulating genital hemodynamics, smooth muscle
      contractility, and neurotransmitter receptor expression. A comprehensive and
      integral understanding of female sexual function requires detailed investigation
      of the vascular, neurological (central and peripheral), and structural components
      of this complex physiological process.

PMID- 12238606
TI  - Sex hormones and neural mechanisms.
AB  - Sex steroids play important and diverse roles in the regulation of structure and
      function of the central nervous system. Early in life, steroids shape the
      structure of sensitive areas of the brain, especially those involved in the
      control of reproductive behavior and ovarian function. Original studies
      demonstrating organizing effects of steroids on the brain were carried out in
      rodents, but more recently these studies have been extended to primates,
      including humans. Throughout life, sex steroids regulate neural function by
      influencing steroid receptor-bearing neurons and by influencing neurons via
      steroid receptor-independent mechanisms. Sex steroid receptors have been
      identified in the brain, especially in the phylogenetically ancient structures
      that regulate reproductive behavior. Sex steroids that affect neural function can
      originate peripherally from the brain and/or adrenal gland, and can be
      synthesized within the brain itself. A number of neurally active progestogens and
      androgens are synthesized de novo in the brain, and estrogens can be converted
      within the brain from androgens by the enzyme aromatase. Thus, ovarian and
      central nervous system sex steroids play important roles in regulating
      reproductive behavior by regulating neural structure and function.

PMID- 12238607
TI  - The physiology of sexual arousal in the human female: a recreational and
      procreational synthesis.
AB  - Changes induced by human sexual arousal serve reproductive and recreational
      functions. The current sexual phase model (desire, excitation, orgasm, and
      resolution) conveys little about this duarchy. Lack of spontaneous sexual desire
      in a third of nonclinic females indicates that the D phase needs splitting into
      D1 (the spontaneous [endogenous] activation of desire) and D2 (desire activated
      by sexual excitation at and during the E phase). Attempts to link D1 with
      reproduction by studies monitoring it over the menstrual cycle revealed a D1 peak
      just before or at ovulation, but its reliability is criticized because of the
      poor identification of the time of ovulation. Sexual arousal initiates enhanced
      genital blood flow, leading to the formation of a neurogenic transudate,
      lubricating the vagina, partly buffering its acidity, and increasing its oxygen
      tension all features that enhance spermatozoal function and survival. Orgasm
      occurs with vaginal and uterine contractions. The latter have been misinterpreted
      as powering rapid sperm transport to facilitate fertilization, but such fast
      transport would lead to the tubal deposition of noncapacitated, incompetent
      spermatozoa. Vagino-cervico elevation, however, delays rapid sperm transport and
      allows the initiation of decoagulation and sperm capacitation before the
      elevation resolves. The fastest transport of spermatozoa from cervix to the
      fallopian tubes occurs in the nonaroused female by uterine/subendometrial smooth
      muscle peristalsis. There is some evidence that even this may be reduced for a
      time after coitus, adding to the transport delay. If a number of the changes
      induced by sexual arousal are inadequately expressed, sexual as well as
      reproductive dysfunctions could arise.

PMID- 12238608
TI  - Defining the brain systems of lust, romantic attraction, and attachment.
AB  - Mammals and birds have evolved three primary, discrete, interrelated emotion
      motivation systems in the brain for mating, reproduction, and parenting: lust,
      attraction, and male-female attachment. Each emotion-motivation system is
      associated with a specific constellation of neural correlates and a distinct
      behavioral repertoire. Lust evolved to initiate the mating process with any
      appropriate partner; attraction evolved to enable individuals to choose among and
      prefer specific mating partners, thereby conserving their mating time and energy;
      male-female attachment evolved to enable individuals to cooperate with a
      reproductive mate until species-specific parental duties have been completed. The
      evolution of these three emotion-motivation systems contribute to contemporary
      patterns of marriage, adultery, divorce, remarriage, stalking, homicide and other
      crimes of passion, and clinical depression due to romantic rejection. This
      article defines these three emotion-motivation systems. Then it discusses an
      ongoing project using functional magnetic resonance imaging of the brain to
      investigate the neural circuits associated with one of these emotion-motivation
      systems, romantic attraction.

PMID- 12238609
TI  - Central nervous system based neurogenic female sexual dysfunction: current status
      and future trends.
AB  - The amount of information available regarding the impact of various central
      nervous system disorders on female sexual function has greatly increased. In this
      article, the most recent information regarding brain and spinal cord disorders in
      human females is reviewed. Evidence from women with spinal cord injuries (SCIs)
      supports findings in able-bodied females that the sympathetic nervous system
      provides regulation of psychogenic sexual arousal. In women with SCIs, the
      ability to achieve orgasm persists in approximately 50%; however, there is a
      relative inability to achieve orgasm with complete disruption of the sacral
      reflex arc. These natural effects of injury should be considered when educating
      patients about neurogenic sexual dysfunction and when developing treatment
      protocols. Published research protocols aimed at improving sexual responsiveness
      and future possibilities for treatment of neurogenic sexual dysfunction are also
      discussed.

PMID- 12238610
TI  - The female sexual pain disorders: genital pain or sexual dysfunction?
AB  - Vaginismus and dyspareunia have been typically classified as sexual dysfunctions.
      In practice and research, this conceptualization has led to a focus on sexual and
      interpersonal issues after biological causes were excluded. Although this
      approach has been very useful, it has not led to significant theoretical or
      therapeutic progress in the last 20 years. We propose a reconceptualization of
      vaginismus and dyspareunia as pain disorders that interfere with sexuality rather
      than as sexual disorders characterized by pain. This reconceptualization focuses
      the clinician and researcher on the central phenomenon-pain. It also suggests new
      approaches to research and treatment. Data from diagnostic, etiologic, and
      therapeutic studies will be presented to illustrate these points.

PMID- 12238611
TI  - The impact of aging on sexual function in women and their partners.
AB  - Aging has a powerful impact on the quality of relationship and sexual
      functioning. The psychological impact of aging after midlife is a particularly
      timely topic, given improved medical and psychological understanding of sexuality
      in both women and men as well as significant improvement in the conceptualization
      of female sexuality and evolving treatment advances for female sexual
      dysfunctions. It is time to dispel the stereotype of the midlife woman in order
      to more effectively address emotional and sexual issues arising in her
      relationships. Regardless of the length or nature of the relationship, its
      quality is enhanced by emotional intimacy, autonomy without too much distance, an
      ability to manage stress, and to maintain a positive perception of self and the
      relationship. To understand and treat effects of aging on sexuality, it is
      important to address the three components of sexual desire: drive,
      beliefs/values, and motivation, as well as the social context of a woman's life.
      It is also essential to understand how the physiological changes in female as
      well as male sexual functioning impact desire. Further, other health-related
      changes that occur with aging must be recognized and addressed.

PMID- 12238612
TI  - Sexual function assessment and the role of vasoactive drugs in female sexual
      dysfunction.
AB  - Despite the high prevalence of sexual problems in women, relatively few clinical
      trials have been conducted to date of either vasoactive drugs (e.g., sildenafil,
      apomorphine) or hormone replacement therapy or a combination of the two on sexual
      function problems in women. This article addresses the key conceptual and
      methodological issues to be addressed in clinical trials, particularly in the
      area of response outcomes or efficacy assessment. In particular, the use of self
      report questionnaires and event-log or diary-based responses as primary outcome
      variables or endpoints in clinical trials is considered. Physiological measures,
      such as the vaginal photoplethysmograph probe, are being used in early proof of
      concept studies. There may be some value in the use of these measures for proof
      of-concept and early dose-finding studies. Physiological measures are not used in
      large-scale, multicenter clinical trials, where patient-based or diary measures
      are clearly preferable. Clinical trials in this area should also make use of the
      new consensus classification system for female sexual dysfunction in determining
      inclusion and exclusion criteria for the trial.

PMID- 12238613
TI  - Psychologic treatments for female sexual dysfunction: are they effective and do
      we need them?
AB  - Most successful treatments for sexual dysfunction are psychophysiological, in
      that physiological change circularly interacts with a psychological change. The
      topic of this article is female sexual dysfunction treatments that are
      psychologic, defined as interventions whose primary vector of action is initiated
      through psychological mechanisms in contrast to physiologic treatments initiated
      through a physical act on the body. In the enthusiasm for new physiologic
      approaches, there has been a strong tendency to overlook or dismiss the evidence
      that does exist for efficacious or promising psychologic treatments. Each
      diagnostic category of desire, arousal, orgasm, and pain disorders is briefly
      reviewed with respect to efficacious or effective criteria. The review shows
      there to be limited controlled research, with only orgasmic disorders meeting the
      more stringent "well established" criteria, promising but uncontrolled results
      for vaginismus and dyspareunia, minimal effectiveness data for hypoactive sexual
      desire disorder, and no available efficacy data on female sexual arousal disorder
      and sexual aversion. It is concluded that (a) since a psychologic treatment can
      and does impact sexual physiology, we need to continue to develop and test
      psychologic approaches both out of intellectual interest and out of respect for
      the choices patients require or prefer, (b) the prescription of a physiologic
      treatment which ignores the fact that human sexuality is infused with individual
      meaning may invite further interference with sexual functioning, and (c) future
      research would do well to test the efficacy of the psychologic and physiologic
      treatments, both separately and in combination, for female sexual dysfunction.

PMID- 12238614
TI  - The medicalization of female sexual dysfunction: the need for caution.
AB  - The use of drugs such as Viagra to treat sexual dysfunction in women may be
      beneficial in a proportion of cases. However, there are a number of barriers to
      understanding and predicting which women are likely to benefit, and caution is
      required in approaching this clinical issue. Three relevant issues are discussed:
      (1) Male-female differences in sexuality. Three complimentary ways in which male
      and female sexuality differs are considered--women have less need for their
      sexuality to be influenced by reproductive hormones; their needs for sexual
      enjoyment and orgasm are not well met by conventional vaginal intercourse; and,
      as a result of the disjunction between female sexual response and reproduction
      and a possibly greater propensity for central inhibition of sexual response,
      women are more susceptible to the repressive effects of social constraints on
      sexuality; (2) Sex therapy. While conventional forms of sex therapy are well
      designed to address the particular psychological needs of women as well as men,
      the interface between psychological processes and physiological response is not
      well understood. For the same reason, we should expect difficulty in predicting
      when pharmacological effects on sexual response will be beneficial; (3) When is a
      sexual problem a sexual dysfunction? It is likely that many cases of impaired
      sexual response or interest in women are psychologically understandable and hence
      adaptive reactions to problems in the sexual relationship, and hence not
      dysfunctions. Until we can distinguish between such adaptive inhibitions of
      response and those that are maladaptive dysfunctions, we will have difficulty in
      predicting when pharmacological treatment will be helpful.

PMID- 12238615
TI  - Inhibition of rat glioma growth by neomycin. Preliminary report.
AB  - Tumor development is known to largely depend on angiogenesis, and nuclear
      translocation of angiogenic factors is one of the crucial steps in tumor
      angiogenesis. This preliminary study was designed to investigate the suppression
      of tumor growth by neomycin, an inhibitor of nuclear translocation of several
      angiogenic factors overexpressed in gliomas. We found that intratumoral osmotic
      pump delivery of 10 mM neomycin caused significant inhibition of C6 glioma tumor
      development (85%) in rats. The data establish neomycin as a potential inhibitor
      of angiogenesis-dependent tumor growth and raise the possibility for its use as
      therapy in pathologies in which neovascularization is involved, including
      neoplasia.

PMID- 12238616
TI  - Localization of ictal and interictal bursting epileptogenic activity in focal
      cortical dysplasia: agreement of magnetoencephalography and electrocorticography.
AB  - Focal cortical dysplasia (FCD) is often associated with severe partial epilepsy.
      In such cases, interictal frequent rhythmic bursting epileptiform activity
      (FBREA) on both scalp electroencephalography (EEG) and electrocorticography
      (ECoG) is generally accepted to be identical to the ictal epileptiform activity.
      We used magnetoencephalography (or Magnetic Source Imaging (MSI)) to determine
      the epileptogenic zone in a 6-year-old patient with histopathologically proven
      FCD and normal magnetic resonance imaging (MRI). MSI was used to localize the
      sources of both ictal activity and FRBEA, which was then compared with ECoG
      findings. The intracranial sources of both types of activity co-localized in the
      left inferior frontal and superior temporal gyri. The location and extent of the
      epileptogenic area determined by MSI was essentially identical to that determined
      directly through extra-operative ECoG. In the absence of structural abnormalities
      detectable on MRI, the noninvasive method of MSI provided valuable information
      regarding the location and extent of the primary epileptogenic area. This was
      critical for pre-surgical planning regarding placement of intracranial electrodes
      and for risk-benefit evaluation.

PMID- 12238617
TI  - Feasibility and limitations of magnetoencephalographic detection of epileptic
      discharges: simultaneous recording of magnetic fields and electrocorticography.
AB  - Magnetoencephalography (MEG) is considered clinically useful in localizing the
      epileptogenic focus in partial epilepsy. However, the relationship between the
      extent of the brain involved in paroxysmal activities and the magnetic field
      changes at the scalp has not been fully clarified. Furthermore, whether
      paroxysmal activities generated in deep brain structures such as the hippocampus
      can be detected magnetically is uncertain. Eight patients with temporal lobe
      epilepsy and two with extratemporal lobe epilepsy underwent chronic recording
      from subdural electrodes. Magnetic and electrocorticographic discharges
      representing epileptic activity were recorded simultaneously. MEG recorded
      magnetic field changes originating from paroxysmal activity in the superiolateral
      cerebral cortex when the amplitudes of the electrical paroxysmal activities
      exceeded 100 microV and extended over more than 3 cm2 of cortical surface. MEG
      failed to record paroxysmal activity localized to the medial temporal lobe. MEG
      is often useful in identifying a spike focus in the superiolateral aspects of the
      cerebral hemisphere, but not discharges arising from the medial temporal lobe.
      Rapid decay of the magnetic field is likely to be the reason for this limited
      sensitivity to medial discharges.

PMID- 12238618
TI  - Proton MR spectroscopy and diffusion-weighted MR imaging for the diagnosis of
      intracranial tuberculomas. Report of two cases.
AB  - With the current prevalence of tuberculosis, the incidence of intracranial
      tuberculoma may be on the rise in industrialized nations. However, clinical
      findings suggestive of systemic tuberculosis are frequently subtle or absent in
      patients with intracranial tuberculoma, and no specific neuroradiologic
      characteristics of tuberculoma have been defined as yet. We report two cases of
      ring-enhanced intracranial tuberculoma in which magnetic resonance (MR) proton
      spectroscopy and diffusion-weighted (DW) imaging were useful in the differential
      diagnosis between tuberculoma and other ring-enhanced mass lesions. Pulmonary
      tuberculosis had been diagnosed in one patient, but radiologic lung study and
      tuberculin skin test were negative in the other. DW imaging showed bright signal
      intensity in the core of all lesions in both patients. Malignant gliomas and
      metastatic brain tumors do not have this characteristic. Proton MR spectroscopy
      of lesion cores showed lipid peaks and a choline peak in one, and a lipid/lactate
      mixture pattern in the other, which differed distinctively from those of the
      pyogenic brain abscess. in each case, one lesion was surgically removed.
      Antituberculosis drugs were started before surgery for one patient and after
      surgery for the other. In both, the remaining lesions were reduced significantly
      in size. We discuss the diagnostic potential of these MR techniques and
      management options of intracranial tuberculoma.

PMID- 12238619
TI  - Intra-operative microrecording equipment: comparative analysis of commercially
      available microrecording systems.
AB  - Intra-operative microrecording is an important and complex part of various
      neurosurgical procedures in the field of functional neurosurgery, primarily
      stereotactic destructive and neuromodulative operations for treatment of movement
      disorders. The growing demand for quality microrecording devices has resulted in
      the development and marketing of several commercially available systems. We
      analyzed several of these systems and compared them with each other, trying to
      emphasize their strong and weak features, in the hope that this analysis will
      help surgeons choose the microrecording system appropriate for the needs and
      preferences of each particular user. Just as every stereotactic surgeon should be
      familiar with the principles of stereotaxis and the details of the particular
      stereotactic frame he or she is using, it is essential for neurosurgeons in this
      field to understand the principles of microrecording and certain technical
      details of the recording equipment in order to avoid major instrumentation
      related malfunctions and to be able to perform on-site troubleshooting if such a
      malfunction occurs.

PMID- 12238620
TI  - Brain tissue oxygenation monitoring supplementary to somatosensory evoked
      potential monitoring for aneurysm surgery. Initial clinical experience.
AB  - The object of the study was to evaluate brain tissue oxygenation (p(ti)O2) for
      intra-operative monitoring of critical ischemic events during early cerebral
      aneurysm surgery of the anterior circulation supplementary to somatosensory
      evoked potentials (SEPs). P(ti)O2 was continuously evaluated during surgery for
      an intracranial aneurysm in 28 patients. Standard cortical SEP monitoring was
      simultaneously performed. The two monitoring methods were compared by evaluating
      their respective responses to intra-operative events (particularly temporary
      vessel occlusion), clinical and neuroradiological outcome. P(ti)O2 and SEPs were
      reliably used for monitoring in 16 patients. Seven patients were excluded due to
      too high or too low p(ti)O2 readings or initial absence of SEPs (six patients).
      Of 64 intra-operative events 19 events (eight patients) were associated with a
      significant decrease in p(ti)O2 (below 10 mmHg), 22 events (13 patients) were
      associated with a significant change in SEP amplitude (< 50% decrease related to
      baseline). Temporary vessel occlusion (six SEP andp(ti)O2 changes each in
      eightpatients) and surgical dissection were most likely to be followed by
      significant changes in a monitoring method. Intra-operative p(ti)O2 was found to
      be a safe, rapid method for documenting ischemic events. P(ti)O2 was found to
      supplement SEP monitoring. The use of p(ti)O2 measurement as a routine monitoring
      method in aneurysm surgery is limited by its focal spatial resolution.
      Nevertheless, it might be helpful as an adjunct in situations when SEPs are
      absent at baseline, in aneurysms when parent vessel anatomy is complex or if
      temporary vessel occlusion is planned.

PMID- 12238621
TI  - Temporal lobe epilepsy and corpora amylacea in the hippocampus: clinicopathologic
      correlation.
AB  - Corpora amylacea (CoA) have been found in about 60% of neurosurgical specimens
      showing hippocampal sclerosis (HS). To determine clinical and neuroimaging
      differences between HS with and without CoA, we studied 29 patients (21 male, 8
      female; age at surgery, 12 to 49 years) who underwent anterior temporal lobectomy
      for intractable medial temporal lobe epilepsy. No CoA were noted in the
      hippocampus of 11 cases, and deposition of CoA was mild and limited to the
      subependymal and vestigial hippocampal sulcus regions in nine cases; in nine
      cases, moderate to marked deposition was noted in the pyramidal cell layer,
      accompanying severe neuronal loss. No significant differences were evident
      between these three groups for age at onset, frequency and duration of epileptic
      seizures, the average age at surgery, or surgical results. Hippocampal
      hyperintensity in fluid-attenuated inversion recovery magnetic resonance images
      tended to increase with increasing hippocampal deposition of CoA. Formation of
      CoA appears to be a response to neuronal loss in the pyramidal cell layer, being
      related to the epileptogenic process as a consequence rather than a cause.

PMID- 12238622
TI  - Post-partum cerebral angiopathy: repetitive TCD, MRI, MRA, and EEG examinations.
AB  - We report of a woman with post-partum cerebral angiopathy (PCA), in whom we
      repetitively performed transcranial Doppler sonography (TCD), MR imaging (MRI),
      and MR angiography (MRA) to evaluate the underlying pathophysiology. A 31-year
      old woman, Gemini pregnant, complained of severe throbbing frontal headache four
      days after an uneventful delivery by Cesarean section. Blurred vision occurred
      eight days after delivery, followed by three generalized tonic-clonic seizures.
      Neurological examination revealed a somnolent woman without focal neurological
      deficits. At the day of the seizures increased flow velocities and disturbed flow
      were observed in the right posterior and anterior cerebral artery on transcranial
      Doppler (TCD). MRI showed infra- and supratentorial patchy hyperintensities in T2
      weighted images and in the FLAIR sequence. Diffusion-weighted imaging revealed
      corresponding multi-focal hyperintense areas indicating increased diffusion and
      MRA showed a diffuse multisegmental narrowing of all pial arteries. MRI at day 10
      was completely normal, but MRA still revealed vascular narrowing in the right
      posterior cerebral artery. General slight flow accelerations in all basal
      arteries occurred after 10 days and lasted for three weeks. PCA is apparently
      associated with a vascular narrowing causing cerebral ischemia with increased
      diffusion. Later reactive cerebral hyperperfusion is observed. Vascular narrowing
      and cerebral hyperperfusion still persist after MRI has normalized.

PMID- 12238623
TI  - Neuroprotective actions of FK506 and cyclosporin A on motor neuron survival
      following neonatal axotomy.
AB  - We show that nonimmunosuppressive analogues of the immunosuppressive drugs FK506
      and cyclosporin A (CsA) rescue axotomized neonatal motor neuron death. Unilateral
      sciatic nerve was transected in neonatal rats. Animals were then treated daily
      with different doses of FK506 and CsA for 14 days with intraperitoneal injection.
      Control rats received phosphate buffer saline (PBS) in the same fashion. After
      treatment, the number of spinal motor neurons was determined at L4 level. In
      comparison with vehicle, both FK506 (5.0 mg kg(-1)) and CsA (10.0 mg kg(-1))
      rescued motor neuron death in a similar way. These results indicate therapeutic
      relevance in the treatment of damaged motor neuron disorders, such as motor
      neuropathy or amyotrophic lateral sclerosis.

PMID- 12238624
TI  - Tardive decrease of astrocytic glutamate transporter protein in transgenic mice
      with ALS-linked mutant SOD1.
AB  - The expressions of glutamate transporter proteins were immunocytochemically
      examined in the spinal cord of transgenic mice harboring a Gly93 --> Ala (G93A)
      mutant human SOD1 gene. Astroglial EAAT2 protein level was preserved in the
      ventral horn even after the beginning of paralysis, and finally decreased at
      terminal stage of the disease (35 weeks of age), when neuronal EAAT3 protein
      level was also decreased. In contrast, glial fibrillary acidic protein (GFAP)
      immunoreactivity progressively increased from 25 weeks of age in the ventral
      horn. The present results show interesting dissociative expressions of astroglial
      proteins EAAT2 and GFAP in the same ventral horn, but suggest not an early and
      primary role of EAAT2 in the motoneuronal death of this model.

PMID- 12238625
TI  - The relation between cerebral blood flow velocities as measured by TCD and the
      incidence of delayed ischemic deficits. A prospective study after subarachnoid
      hemorrhage.
AB  - Patients (n = 127) with aneurysmal subarachnoid hemorrhage (SAH) were examined by
      transcranial Doppler ultrasonography (TCD) in a prospective study to follow the
      time course of the posthemorrhagic blood flow velocity in both the middle
      cerebral artery (MCA) and in the anterior cerebral artery (ACA). Results were
      analysed to reveal their relationship and predictive use with respect to the
      occurrence of delayed ischemic deficits. Mean flow velocities (MFV) higher than
      120 cm sec(-1) in MCA and 90 cm sec(-1) in ACA were interpreted as indicative for
      significant vasospasm. In 20 of our 127 patients (16%) a delayed ischemic deficit
      (DID) was subsequently diagnosed clinically (DID+ group). Patients in the DID+
      group can be characterized as those individuals who presented early during the
      observation period post-SAH with highest values of MFV, a faster increase and
      longer persistence of pathologically elevated MFV-values (exceeding 120 cm sec(
      1) in MCA and 90 cm sec(-1) in ACA). They also show a greater difference in MFV
      values if one compares the operated to the nonoperated side. Differences in MFV
      values obtained in MCA or ACA were statistically significant (p < 0.05) for DID+
      and DID- patients. The daily maximal increase of MFV was found between days 9 and
      11 after SAH. In the DID+ group, the maximal MFV was 181 +/- 26 cm sec(-1) in MCA
      and 119 +/- 14 cm sec(-1) in ACA. In contrast to this, patients in the DID- group
      were found to present with MFV of 138 +/- 11 cm sec(-1) in MCA and 100 +/- 7 cm
      sec(-1) in ACA respectively. Delayed ischemic deficits appeared three times more
      often in DID+ patients than in patients with MFV < 120 cm sec(-1), if they showed
      a MFV > 120 cm sec(-1) in MCA. If pathological values were obtained in ACA, this
      ratio increases to about four times, if DID + patients presented with MFV > 90 cm
      sec(-1) versus patients with MFV < 90 cm sec(-1). Daily monitoring of vasospasm
      using TCD examination is thus helpful to identify patients at high risk for
      delayed ischemic deficits. This should allow us to implement further preventive
      treatment regimens.

PMID- 12238626
TI  - Temporal and spacial changes of BrdU immunoreactivity in amygdala kindling
      development.
AB  - To investigate the proliferation of neural stem cells (NSC) in epileptic brain,
      spaciotemporal expression of immunoreactive bromodeoxyuridine (BrdU) was examined
      in kindling development of rat. Amygdaloid kindling in partial seizure (PS) was
      effective in proliferation of NSC detected with BrdU-labeling in subventricular
      zone (SVZ), but not in dentate gyrus (DG). In SVZ, however, the BrdU-labeling
      cells decreased at stage generalized seizure (GS). These facts indicate that
      proliferation of NSC increased with PS and decreased with more severe seizures of
      GS in SVZ, that such a proliferation did not occur in DG with PS or GS. Thus, the
      proliferation of NSC was spacially and temporally different between brain regions
      depending on different kindling stages.

PMID- 12238627
TI  - Velocity of microemboli and transit time from the heart to the brain in patients
      with patent foramen ovale and artificial heart valves.
AB  - There is no information about the physical behavior of microemboli en route from
      their source to the cerebral vessels. Microemboli could abide to a certain
      laminae, and have a consistent velocity, or wander between different laminae, and
      keep changing their velocity. Two hundred and seventy four microemboli were
      recorded by transcranial Doppler (TCD) in six patients with artificial valves,
      and 119 microemboli were recorded in response to i.v. injection of saline
      agitated with air in eight patent foramen ovale (PFO) patients. Transit time of
      microemboli, calculated based on their arrival time at the cerebral vessel (site
      of monitoring) was explored as a possible function of their measured velocity at
      the detection point. In the PFO group, the relation between embolus velocity and
      transit time was: embolus velocityPFO = -41.8 * transit time + 100.6, whereas for
      the artificial heart valve group it was: embolus velocityValve = -22.6 * transit
      time + 67.1. Transit time, in both clinical groups, was inversely related to
      velocity (p < 0.001), thus, early appearing emboli had higher velocity and vice
      versa. The inverse relation between transit time and measured terminal velocity
      implies a consistent velocity per microemboli en route, in both groups. Thus, a
      flow abided to a certain laminae seems to characterize microemboli.

PMID- 12238628
TI  - 5-Hydroxyindolacetic acid and homovanillic acid are not involved in the
      cerebrospinal fluid after a seizure in patients with Delirium Tremens.
AB  - Little is known about 5-hydroxyindolacetic acid (5-HIAA) and homovanillic acid
      (HVA) levels in cerebrospinal fluid of patients with Delirium Tremens revealed at
      onset by seizures. The aim of the study is to understand the biochemical
      abnormalities induced by seizures in the cerebrospinal fluid of patients involved
      by Delirium Tremens. Nine patients 42-62 years of age, who had experienced a
      Delirium Tremens after alcohol withdrawal, with one or two seizures at onset,
      were included in this study. The lumbar puncture (and a CT scan) were performed
      after the last seizure. Nine patients with neither Delirium Tremens nor seizure,
      needing a lumbar puncture for their medical problem, were matched by sex and by
      age. For the measures of 5-HIAA and HVA, we systematically took the first cm3.
      The mean value of 5-HIAA levels were 12.70 ng ml(-1) in the group of nine
      patients with Delirium Tremens versus 13.45 ng ml(-1) in the control group. The
      mean value of HVA levels were 19.81 ng ml(-1) in the group of nine patients with
      Delirium Tremens versus 25.25 ng ml(-1) in the control group. The differences
      were not statistically significant. During a Delirium Tremens with seizure at
      onset, there are no statistically significant changes in 5-HIAA and HVA levels in
      the cerebrospinal fluid. Our work raises the question of the role of Delirium
      Tremens in the normalization of the levels of neuro-mediators that usually
      decrease soon after seizures.

PMID- 12238629
TI  - Influence of inspired oxygen on glucose-lactate dynamics after subdural hematoma
      in the rat.
AB  - The mechanisms causing brain damage after acute subdural hematoma (SDH) are
      poorly understood. A decrease in cerebral blood flow develops immediately after
      the hematoma forms, thus reducing cerebral oxygenation. This in turn may activate
      mitochondrial failure and tissue damage leading to ionic imbalance and possibly
      to cellular breakdown. The purpose of this study was to test whether a simple
      therapeutic measure, namely increased fraction of inspired oxygen (FiO2 100), and
      hence increased arterial and brain tissue oxygen tension, can influence brain
      glucose and lactate dynamics acutely after subdural hematoma in the rat. Twenty
      five male Sprague-Dawley anesthetized rats were studied before, during and after
      induction of the SDH in two separate groups. The Oxygen group (n = 10) was
      ventilated with 100% oxygen immediately after induction of the SDH. The Air group
      (n = 10) was ventilated during the entire study with 21% oxygen. Brain
      microdialysate samples were analyzed for glucose and lactate. All rats were
      monitored with femoral arterial blood pressure catheters, arterial blood gas
      analysis, arterial glucose, lactate and end tidal CO2 (EtCO2). Five male Sprague
      Dawley rats were sham operated to measure the effect of oxygen challenge on
      glucose-lactate dynamics without injury. Arterial oxygen tension in the Oxygen
      group was 371 +/- 30 mmHg and was associated with significantly greater increase
      in dialysate lactate in the first 30 min after induction of SDH. Dialysate
      glucose initially dropped in both groups, after SDH, but then reverted
      significantly faster to values above baseline in the Oxygen group. Changes in
      ventilatory parameters had no significant effect on dialysate glucose and lactate
      parameters in the sham group. Extracellular dialysate lactate and glucose are
      influenced by administration of 100% O2 after SDH. Dialysate glucose normalizes
      significantly quicker upon 100% oxygen ventilation. We hypothesize that increased
      neural tissue oxygen tension, in presence of reduced regional CBF, and possibly
      compromised mitochondrial function, after acute SDH results in upregulation of
      rate-limiting enzyme systems responsible for both glycolytic and aerobic
      metabolism. Similar changes have been seen in severe human head injury, and
      suggest that a simple therapeutic measure, such as early ventilation with 100%
      O2, may improve cerebral energy metabolism, early after SDH. Further studies to
      measure the generation of adenosine triphosphate (ATP) are needed to validate the
      hypothesis.

PMID- 12238630
TI  - Type V phosphodiesterase expression in cerebral arteries with vasospasm after
      subarachnoid hemorrhage in a canine model.
AB  - Cyclic GMP (cGMP) mediates smooth muscle relaxation in the central nervous
      system. In subarachnoid hemorrhage (SAH), decreases in intrinsic nitric oxide
      (NO) cause cerebral vasospasms due to the regulation of cGMP formation by NO
      mediated pathways. As phosphodiesterase type V (PDE V) selectively hydrolyzes
      cGMP, we hypothesized that PDE V may function in the initiation of vasospasm.
      This study sought to identify the altered PDE V expression and activity in the
      vasospastic artery in a canine SAH model. We also used this system to examine
      possible therapeutic strategies to prevent vasospasm. Using a canine model of
      SAH, we induced cerebral vasospasm in the basilar artery (BA). Following
      angiographic confirmation of vasospasm on day 7, PDE V expression was
      immunohistochemically identified in smooth muscle cells of the vasospastic BA but
      not in cells of a control artery. The isolation of PDE enzymes using a sepharose
      column confirmed increased PDE V activity in the vasospastic artery only through
      both inhibition studies, using the highly selective PDE V inhibitor, sildenafil
      citrate, and Western blotting. Preliminary in vivo experiment using an oral PDE V
      inhibitor at 0.83 mg kg(-1) demonstrated partial relaxation of the spastic BA.
      PDE V activity was increased from control levels within the BA seven days after
      SAH. PDE V expression was most prominent in smooth muscle cells following SAH.
      These results suggest that clinical administration of a PDE V inhibitor may be a
      useful therapeutic tool in the prevention of vasospasm following SAH.

PMID- 12238632
TI  - Effects of hypothermia and rewarming on evoked potentials during transient focal
      cerebral ischemia in cats.
AB  - We examined the effects of mild to moderate hypothermia and the influence of
      rewarming on electrophysiological function using somatosensory evoked potentials
      (SEPs) in transient focal ischemia in the brain. Nineteen cats underwent 60 min
      of left middle cerebral artery occlusion under normothermic (36 degrees-37
      degrees C, n = 6) or hypothermic (30 degrees -31 degrees C, n = 13) conditions
      followed by 300 min of reperfusion with slow (120 min, n = 6) or rapid (30 min, n
      = 7) rewarming. Whole-body hypothermia was induced during ischemia and the first
      180 min of reperfusion. SEPs and regional cerebral blood flow were measured
      before and during ischemia and during reperfusion. The specific gravity of gray
      and white matter was examined as the indicator of edema. During rewarming, SEP
      amplitudes recovered gradually. After rewarming, SEPs in the normothermic and
      rapid rewarming groups remained depressed (20%-40% of pre-occlusion values);
      however, recovery of SEPs was significantly enhanced in the slow rewarming group
      (p < 0.05). Hypothermia followed by slow rewarming reduced edema in gray and
      white matter. Rapid rewarming did not reduce edema in the white matter. The
      recovery of SEPs correlated with the extent of brain edema in transient focal
      ischemia. Rapid rewarming reduced the protective effect of hypothermia.

PMID- 12238631
TI  - Tolerability of bolus versus continuous gastric feeding in brain-injured
      patients.
AB  - Brain injured patients may exhibit altered gastric emptying; thus, some believe
      post-pyloric feeding to be tolerated better than gastric feeding. Reliable post
      pylorus access can be difficult to obtain, so gastric feeding remains the
      preferred route for administering nutrition. Feeding intolerance may be
      associated with increased complications and costs. We sought to compare bolus (B)
      versus continuous (C) gastric feeding in brain injured patients. This
      retrospective cohort study was carried out at a neurological/neurosurgical
      intensive care unit at a Level 1 trauma and tertiary referral center. Our
      subjects were 152 consecutive patients over two years. Use of B or C feedings was
      based on clinicians' preferences. Abdominal examination and gastric residuals (>
      75 mL over four hours) defined feeding intolerance (FI). Putative risks for FI
      were compared between the groups. Demographic characteristics were similar
      between groups B (n = 86) and C (n = 66). Feeding intolerance occurred more often
      in group B than in group C (60.5% vs. 37.9%, p = 0.009). Group C patients
      achieved 75% of nutritional goals faster than group B patients (median 3.3 vs.
      4.6 days; p = 0.03). Prokinetic agent use was similar between the groups and did
      not reduce the time to achieve nutritional goals. There was a trend towards a
      reduction in the incidence of infections in group C (p = 0.05). Independent
      predictors of FI included: sucralfate (OR 2.3), propofol (OR 2.1), pentobarbital
      (OR 3.9) or paralytic (OR 3) use; older age (OR 5); days receiving mechanical
      ventilation (OR 1.2); and admission diagnosis of either intracerebral hemorrhage
      (OR 2.2) or ischemic stroke (OR 1.9). Continuous gastric feeding is better
      tolerated than B feedings in patients with acute brain injuries. Use of
      prokinetic agents did not affect time to achievement of nutritional goals. Use of
      common medications including sucralfate and propofol were associated with FI.

PMID- 12238633
TI  - Plasma concentrations of atrial and brain natriuretic peptides in a case with
      hypertensive encephalopathy.
AB  - Hemodynamic mechanism for brain edema forrmation in patients with hypertensive
      encephalopathy is unclear. Potential roles of natriuretic peptides in the
      pathogenesis of hypertensive encephalopathy are discussed. A 32-year-old man
      presented with slight left hemiparesis. He was slightly confused, and his blood
      pressure was extremely high. Cranial plain computerized tomography scans revealed
      diffuse brain edema mainly in the supratentorial white matter region. Blood
      examination revealed that plasma concentrations of atrial and brain natriuretic
      peptides were significantly high. His left hemiparesis disappeared within a day,
      but he tended to be agitated. His altered mental status, however, resolved with
      control of blood pressure. Serial magnetic resonance imagings demonstrated that
      the magnitude of brain edema was attenuated in proportion to decline in plasma
      concentrations of natriuretic peptides. This case suggests that significant
      elevation of plasma concentrations of natriuretic peptides may contribute to an
      acute rise in blood pressure, and that these peptides potentially play an
      important role in development of brain edema in hypertensive encephalopathy.

PMID- 12238634
TI  - Report of the Japan Atherosclerosis Society (JAS) Guideline for Diagnosis and
      Treatment of Hyperlipidemia in Japanese adults.
AB  - This paper described the Guideline for Diagnosis and Management of
      Hyperlipidemias for Prevention of Atherosclerosis proposed by The Japan
      Atherosclerosis Society (JAS) Guideline Investigating Committee (1,995-2,000)
      under the auspices of the JAS Board of Directors. 1) The guideline defines the
      diagnostic criteria for serum total cholesterol (Table 1), LDL-cholesterol (Table
      1), triglycerides (Table 4) and HDL-cholesterol (Table 7). It also indicates the
      desirable range (Table 1), the initiation levels of management (Table 2) and the
      target levels of treatment (Table 2) for total and LDL-cholesterol. 2) Though
      both total and LDL-cholesterol are shown as atherogenic parameter in the
      guideline, the use of LDL-cholesterol, rather than total cholesterol, is
      encouraged in daily medical practice and lipid-related studies, because LDL
      cholesterol is more closely related to atherosclerosis. 3) Elevated triglycerides
      and low HDL-cholesterol are included in the risk factors, since no sufficient
      data have been accumulated to formulate the guideline for these two lipid
      disorders. 4) Emphasis is laid on evaluation of risk factors of each subject
      before starting any kind of treatment (Table 2). 5) This guideline is applied
      solely for adults (age 20-64). Lipid abnormalities in children or the youth under
      age 19, and the elderly with an age over 65 have to be evaluated by their own
      standard. 6) This part of the guideline gives only the diagnostic aspects of
      hyperlipidemias. The part of management and treatment will follow in the second
      section of the guideline that will be published in future.

PMID- 12238635
TI  - Elevated serum leptin concentrations in women with hyperuricemia.
AB  - The serum uric acid level has been said to be an independent predictor of
      cardiovascular disease death, mainly for women, and to be linked with the
      metabolic Syndrome X of insulin resistance, obesity, hypertension, and
      dyslipidemia. Recently, it has been suggested that the elevation of serum leptin,
      the ob gene product, may have a role in metabolic Syndrome X. Therefore, we
      studied the relationship of uric acid to leptin in 822 Japanese women in a cross
      sectional manner. To estimate the effect of uric acid on the variables of
      metabolic Syndrome X, we calculated mean values of various components of the
      syndrome according to tertiles of uric acid (UA < 4.0 mg/dl, 4.0 < or = UA < 5.5,
      5.5 < or = UA). Age, systolic and diastolic blood pressure (BP), body mass index
      (BMI), percent body fat mass (BFM), serum total cholesterol, triglyceride,
      atherogenic index, leptin, fasting immunoreactive insulin and homeostasis model
      assessment-ratio (HOMA-R: calculated insulin resistance) were significantly
      different across the uric acid tertiles with higher levels in the highest tertile
      in comparison to the first (ANOVA, p < 0.001, 0.001, 0.002, 0.001, 0.001, 0.025,
      0.001, 0.001, 0.001, 0.001, 0.001, respectively), while high density lipoprotein
      cholesterol showed lower levels (p < 0.001). Serum leptin concentrations were
      also elevated in hyperuricemic women after adjusting for BMI or BFM (both p <
      0.001), and were weakly correlated with serum uric acid concentrations (r = 0.22,
      p < 0.0001). BMI, HOMA-R, serum triglyceride, diastolic BP and age-adjusted serum
      leptin concentrations were calculated for each tertile of serum uric acid.
      Compared with the lowest tertile of uric acid level, BMI, HOMA-R, serum
      triglyceride, diastolic BP and age-adjusted leptin concentrations were higher in
      the highest tertile. In the stepwise regression analysis, serum leptin was the
      significant independent variable for uric acid values. These results indicate an
      independent relationship between leptin and uric acid, further supporting the
      involvement of leptin in metabolic Syndrome X.

PMID- 12238636
TI  - Multinucleated variant endothelial cells (MVECs) have a greater capacity for LDL
      cholesterol uptake than typical mononuclear endothelial cells (TECs).
AB  - The existence of large endothelial cells in the human aorta, especially on
      atherosclerotic lesions has been reported. They have multiple nuclei and are
      called "multinucleated variant endothelial cells (MVECs)". In the present study
      caveolin expression was demonstrated in both MVECs and small typical endothelial
      cells (TECs). Caveolin was expressed diffusely as fine particles, and caveoles
      were expressed as prominent accumulations of caveolin in the cytoplasm. LDL was
      bound to the endothelial surface. With double immunostaining for caveolin and
      LDL, the location of LDL corresponded to the immunoreactive caveoles. Over time,
      large dots of LDL appeared in MVECs, whereas a few fine particles remained in
      TECs. An electron microscopic chase study of LDL-gold uptake identified many LDL
      gold particles in plasmalemmal vesicles and in endosomes or lysosomes of MVECs,
      but only a few particles were found in TECs. Gold containing vesicles often were
      located near the abluminal surface. The number of LDL-gold particles was 4.5
      times greater per unit area in MVECs than in TECs. Some of the gold particles
      were located in the subendothelial collagen matrix. These findings indicate that
      MVECs have a greater capacity of LDL cholesterol uptake followed by transport to
      the subendothelial matrices than TECs, and that MVECs contribute to the
      development and advancement of atherosclerotic lesions.

PMID- 12238637
TI  - Low-density lipoprotein particle diameter in normal pregnancy and preeclampsia.
AB  - We investigated the changes of low-density lipoprotein (LDL) size and serum
      lipids during pregnancy and postpartum not only in normal pregnant women but also
      in preeclampsia. Serum triglyceride (TG) and total cholesterol levels as well as
      serum high-density lipoprotein (HDL)-cholesterol, apolipoprotein (Apo) A1, B, E
      and remnant-like particle (RLP)-cholesterol levels were increased in normal
      pregnant women. The LDL peak particle diameter (PPD) in normal pregnant women was
      decreased during pregnancy and that at 37 weeks of gestation showed significant
      decrease compared with the women at 4 weeks after delivery (25.8 +/- 1.0 vs.26.8
      +/- 0.7 nm, p < 0.05). The LDL-PPD in the preeclamptic women at admission (mean
      gestational age: 36 +/- 2.4 weeks) was significantly lower than that in normal
      pregnancy at 37 weeks of gestation (24.7 +/- 1.2 vs. 25.8 +/- 1.0 nm, p < 0.05).
      Moreover, the LDL-PPD in the preeclamptic women was significantly higher after
      delivery compared with the level at admission (27. +/- 0.7 vs. 24.7 +/- 1.2 nm, p
      < 0.05) accompanied by an improvement in plasma lipids profile. These findings
      suggest that the predominance of small, dense LDL, a potential contributor to
      endothelial dysfunction, may be a possible predictor of preeclampsia.

PMID- 12238638
TI  - Clinical effects of rosuvastatin, a new HMG-CoA reductase inhibitor, in Japanese
      patients with primary hypercholesterolemia: an early phase II study.
AB  - The effects and tolerability of the new HMG-CoA reductase inhibitor rosuvastatin
      were assessed in 68 hypercholesterolemic Japanese patients (22 men and 46
      postmenopausal women; age range 28-72 years) in a multicenter, double-blind, dose
      ranging, early phase II study. Patients were randomized into three groups and
      received once-daily doses of 1, 2, or 4 mg rosuvastatin. Sixty evaluable patients
      (19 men and 41 women) with mean total cholesterol (TC) 294 mg/dl (7.60 mmol/l)
      and mean triglyceride (TG) 150 mg/dl (1.69 mmol/l) provided data in the efficacy
      analysis based on percentage changes in lipids at 4 and 8 weeks. All doses of
      rosuvastatin improved lipid parameters after both 4 and 8 weeks of therapy. On
      average, TC decreases were 22-29%, low-density lipoprotein cholesterol (LDL-C)
      decreases 32-42%, TG decreases 2% to 22%, and HDL-C increases 3-7%. There were no
      remarkable differences between efficacy at 4 and at 8 weeks, and dose-dependent
      reductions were noted for LDL-C, with 30, 39, and 42% decreases in the 1-, 2-,
      and 4-mg/ day dose groups, respectively, at 8 weeks. The drug was well tolerated
      over the 8 weeks of therapy. These preliminary results indicate that rosuvastatin
      is a potent cholesterol-lowering agent, capable of achieving marked reductions in
      LDL-C even at low doses.

PMID- 12238639
TI  - Synergically increased expression of CD36, CLA-1 and CD68, but not of SR-A and
      LOX-1, with the progression to foam cells from macrophages.
AB  - Several species of scavenger receptors have so far been identified. However, it
      remains unclear which receptors are more crucial for the foam cell formation and
      progression. In the present study, we compared five major scavenger receptors (SR
      A, CD36, CLA-1, CD68, and LOX-1) in their levels of expression at the different
      stages of foam cells derived from THP-1 cells. The expression of all scavenger
      receptors examined was up-regulated by the stimulation with TPA for 48 hours,
      despite the expressions of SR-A, CD36 and LOX-1 being very low before the
      treatment with TPA. Four to 7 days after the removal of TPA, the levels of CD36,
      CLA-1 and CD68 were increased significantly. In contrast, the expression of SR-A
      was suppressed significantly, and no change was observed in that of LOX-1.
      Furthermore, when the transformed macrophages were incubated with oxidized LDL,
      in which the uptake of [3H] cholesteryl oleoyl ether-labeled OxLDL was linear up
      to 7 days after the addition of OxLDL, the expression of CD36, CLA-1 and CD68
      were greatly enhanced. This enhancement was more prominent than that without
      oxidized LDL, and the enhancement was sustained throughout the experimental
      period. On the other hand, SR-A was not up-regulated, and LOX-1 was down
      regulated. We thus propose that CD36, CLA-1 and CD68, but not SR-A and LOX-1, may
      play crucial roles in the progression of macrophages to foam cells, which is a
      key step for the initiation of atherosclerosis.

PMID- 12238640
TI  - Oxysterol-induced apoptosis of vascular smooth muscle cells is reduced by HMG-CoA
      reductase inhibitor, pravastatin.
AB  - We investigated the mechanism by which 7-ketocholesterol damages vascular smooth
      muscle cells and the protective effect of the hydroxymethyl glutary CoA reductase
      inhibitor, pravastatin on it. When 7-ketocholesterol (50 micromol/L) was added to
      cultured human vascular smooth muscle cells, the extent of cell detachment
      increased and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end
      labeling was positive. DNA extracted from the smooth muscle cells exposed to 7
      ketocholesterol showed a ladder pattern on agarose electrophoresis. The
      fragmented DNA also increased in smooth muscle cells incubated with 7
      ketocholesterol dose-dependently. In the presence of pravastatin, the cell
      detachment induced by 7-ketocholesterol was inhibited and the amount of
      fragmented DNA decreased significantly. These effects of pravastatin were
      inhibited by mevalonate. The results suggest that 7-ketocholesterol-induced
      apoptosis of vascular smooth muscle cells is inhibited by pravastatin, and
      mevalonate acts as a trigger of the apoptosis.

PMID- 12238641
TI  - Atorvastatin reduces plasma levels of factor VII activity and factor VII antigen
      in patients with hyperlipidemia.
AB  - Atorvastatin is a powerful new synthetic 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase inhibitor currently in clinical use. Its effects on plasma levels of
      factor VII were examined in 30 hyperlipidemic patients. After 12 weeks of
      atorvastatin treatment, factor VII activity (FVIIc) and factor VII antigen
      (FVIIag) levels had decreased by 13% (p < 0.0001) and 12% (p < 0.0001),
      respectively. The decreased concentrations of serum triglycerides correlated with
      decreases in FVIIc levels (r = 0.54, p = 0.0023) and FVIIag levels (r = 0.59, p =
      0.0006) at 12 weeks of treatment with atorvastatin. No significant changes were
      seen in activated factor VII (FVIIa) levels. Plasma concentrations of fibrinogen
      were slightly, but not significantly, increased at 12 weeks. No significant
      changes were seen in plasminogen activator inhibitor-1 levels. The effects of
      atorvastatin on FVII may contribute to a decreased thrombotic potential,
      resulting in fewer thromboembolic events, including a reduction in coronary heart
      disease.

PMID- 12238642
TI  - Effects of low intensity aerobic training on skeletal muscle capillary and blood
      lipoprotein profiles.
AB  - The effects of low intensity endurance training on skeletal muscle capillary
      density and serum lipoprotein levels were studied in 11 non-obese men (18-25
      years). The subjects performed a 6-week training regimen (60 min, 5 times per
      week) at the lactate threshold (LT). Capillary density was determined in biopsy
      specimens obtained from the vastus lateralis muscle before and after the
      training. The number of capillaries per fiber (cap/fiber ratio) before training
      was 1.97 +/- 0.47, and increased to 2.49 +/- 0.69 after training (p < 0.05). The
      maximal oxygen uptake (VO2 max) and LT- VO2 increased significantly by 5% (p <
      0.01) and 27% (p < 0.01), respectively, whereas no change was observed in body
      weight. Low density lipoprotein cholesterol (LDL-C) tended to decrease (p =
      0.06). The change in the cap/fiber ratio correlated inversely with the change in
      the ratio of LDL-C to high density lipoprotein cholesterol (HDL-C) (r = -0.61, p
      < 0.05). It was also, positively associated with the change in HDL2-C (r = 0.82,
      p < 0.01) and inversely associated with the change in HDL3-C (r = -0.63, p <
      0.05). The change in LT- VO2 was inversely associated with the change in LDL-C (r
      = -0.62, r < 0.05). These results indicate that low intensity training increases
      capillary density in skeletal muscle, which may explain in part the changes in
      the lipoprotein profiles.

PMID- 12238643
TI  - Peer led HIV prevention among homosexual men in Britain.

PMID- 12238644
TI  - Using the evidence base on genital herpes: optimising the use of diagnostic tests
      and information provision.
AB  - There have been several important advances in the range of available diagnostic
      tests for genital herpes simplex virus (HSV) infection in recent years;
      polymerase chain reaction (PCR) is emerging in routine clinical use and the
      potential role of type specific serological tests is currently under debate.
      Several large trials of prophylactic vaccines, subsequently proved to be
      ineffective, have expanded knowledge of the transmission and epidemiology of HSV
      infection. This article discusses optimal application of recent research evidence
      to clinical care, structured around the key issues for patients and their
      partners. These include acquisition and transmission of genital HSV-1 and HSV-2
      infection, the natural history of genital herpes, and the role of partner
      notification.

PMID- 12238645
TI  - Hepatitis B virus infection among Chinese residents in the United Kingdom.
AB  - OBJECTIVE: To determine prevalence of hepatitis B virus (HBV) serological markers
      in Chinese residents in the United Kingdom. METHOD: Retrospective case-controlled
      study between January 1997 and June 2000 in two genitourinary medicine (GUM)
      clinics. RESULTS: 117 Chinese and 234 non-Chinese controls were studied. Baseline
      characteristics except marital status showed no difference. Overall prevalence of
      HBV serological markers was 35.8% in Chinese, controls 5.5% (p<0.001). Hepatitis
      B surface antigen (HBsAg) positive carrier rate was 12.8% in Chinese, controls
      0.4% (p<0.001); 1.7% of Chinese patients were also hepatitis B e antigen (HBeAg)
      positive, none in controls. Natural immunity was acquired in 23.0% of Chinese,
      controls 5.1% (p<0.001). Prevalence of HBV serological markers in UK born Chinese
      was 6.7%, non-UK born Chinese 40.1% (p<0.011). Only 7.6% of Chinese had a history
      of previous HBV vaccination. CONCLUSIONS: Prevalence of HBV serological markers
      among Chinese patients attending two GUM clinics in London was high and only a
      minority of Chinese had immunisation against HBV. Although the prevalence of HBV
      markers in UK born Chinese was lower than non-UK born Chinese, they may be at
      continuous risk of HBV infection. Non-UK born Chinese patients attending GUM
      services in the United Kingdom should be targeted for screening and vaccination
      to reduce HBV transmission.

PMID- 12238646
TI  - Prevalence and incidence of hepatitis B virus infection in STD clinic attendees
      in Pune, India.
AB  - OBJECTIVES: To estimate the prevalence and incidence of hepatitis B virus (HBV)
      infection among patients attending three STD clinics in Pune, India, and to
      identify associated risk factors. METHODS: Of the 2098 patients screened at STD
      clinics in Pune during 1996, 497, who returned for at least one follow up visit,
      were screened for various markers of HBV infection (HBsAg, anti-HBs, anti-HBc),
      HIV antibody, and VDRL. RESULTS: Of the 497 participants 3.6%, 26.5%, and 43.2%
      were positive for HBsAg, anti-HBs, and anti-HBc respectively. Tattooing (AOR
      1.64, 95% CI 1.03 to 2.64) was found to be independently associated with presence
      of core antibody. Additionally, history of being in commercial sex work and
      history of a genital ulcer were independently associated with a positive anti-HBc
      antibody test (AOR 12.45, 95% CI 5.58 to 27.82 and AOR 1.70, 95% CI 1.09 to 2.66,
      respectively). 72 out of 497 (14.5%) participants were HIV positive at baseline.
      HIV-1 antibody positive patients were more likely to have a positive anti-HBc
      test (69.4% v 39.0%, p<0.001). 30 out of 282 participants, negative for anti-HBc
      antibody at enrolment, seroconverted subsequently, resulting in an incidence of
      10.86 per 100 person years (95% CI 7.2%, 14.5%) (mean and accumulated follow up
      of 11.7 months and 276.17 person years, respectively). CONCLUSIONS: A high
      prevalence and incidence of HBV infection, seen in STD clinic attendees
      underscore the need to provide HBV vaccine to commercial sex workers and their
      clients in India.

PMID- 12238647
TI  - Seroprevalence of hepatitis A immunity in male genitourinary medicine clinic
      attenders: a case control study of heterosexual and homosexual men.
AB  - OBJECTIVES: To compare the seroprevalence of hepatitis A in homosexual and
      heterosexual men to determine their susceptibility to infection and provide
      guidance for a policy on vaccination. METHODS: A case-control study design was
      utilised to compare the risk factors associated with hepatitis A in homosexual
      and heterosexual men attending a city centre genitourinary medicine clinic.
      Demographic and sexual behavioural characteristics were included in univariate
      and multivariate models. RESULTS: The overall seropositivity rate was 29% with no
      significant difference between homosexual and heterosexual men. Ethnicity and age
      were strongly associated with hepatitis A seropositivity in both homosexuals and
      heterosexuals. A history of sex in a sauna in homosexual men, and being born
      outside the United Kingdom for heterosexual men, was associated with hepatitis A
      seropositivity. CONCLUSIONS: Targeted hepatitis A screening and vaccination of
      homosexual men attending UK genitourinary medicine clinics is not supported by
      the results of this study.

PMID- 12238648
TI  - Reasons for not using condoms among the Hong Kong Chinese population:
      implications for HIV and STD prevention.
AB  - OBJECTIVE: To assess the prevalence and reasons for non-use of condoms among the
      Hong Kong Chinese population and obtain baseline data to monitor sexual
      behavioural change. METHODS: Cross sectional self administered questionnaire
      surveys in convenience sampled groups of Hong Kong Chinese residents were carried
      out. RESULTS: Of the 1508 respondents, 24% reported consistent condom use and 76%
      inconsistent use. Overall, 17% of respondents reported having sex with strangers.
      People who were at increased risk for inconsistent condom use included STD
      clinics attendees, those who never married, and those reporting low self efficacy
      for condom use or sex with strangers. Common reasons for not using condoms were
      trust in partner, use of other contraceptives, and reduced sensation while using
      condoms. CONCLUSIONS: Given the reported high prevalence of travel and sexual
      contact with strangers, and misconceptions about condoms among the Hong Kong
      Chinese population, innovative condom social marketing campaigns are needed.
      Periodic monitoring of condom use behaviours should be an integral part of
      HIV/STD surveillance activity.

PMID- 12238649
TI  - TV or not TV?

PMID- 12238650
TI  - The feasibility of integrated STI prevalence and behaviour surveys in developing
      countries.
AB  - BACKGROUND: In countries where STI/HIV prevalence data and behavioural data are
      scarce UNAIDS second generation HIV surveillance guidelines recommend measuring
      STI/HIV prevalence and risk behaviours in vulnerable populations but do not
      recommend conducting these surveys concurrently because of concerns about
      participation rates, cost, and provision of services. OBJECTIVES: To assess the
      feasibility of conducting a national combined STD prevalence and behaviour survey
      in Mali among vulnerable populations with the intention of institutionalisation.
      METHODS: From March to June 2000 an integrated STI prevalence and behaviour
      survey was conducted using cluster sampling among five risk groups in four sites
      in Mali, west Africa. 2229 individuals in non-traditional settings such as
      taxi/bus stations, market areas, households, and brothels participated in any one
      or all components of the study: (1) behavioural questionnaire, (2) urine sample
      for Neisseria gonorrhoeae (GC)/Chlamydia trachomatis (CT) testing, (3) a
      fingerstick drop of blood for syphilis, and/or (4) HIV testing. RESULTS: High
      participation rates of 84%-100% were achieved despite specimen collection and HIV
      testing. Rates fell only slightly when participants were asked to provide
      biological samples and participants were more likely to provide urine than blood.
      Rates among the different groups for HIV and syphilis testing are similar and
      suggest that refusal was most probably because of a reluctance to give blood
      rather than because of HIV testing. The cost of the biological component added
      approximately $30 per participant. Included in the $30 are the costs of training,
      participant services, laboratory personnel and supplies, STI drugs, and STI
      testing costs. The total cost of the survey was $154,905. Biomarkers aided in
      validation of answers to behavioural questions. Consenting individuals received
      HIV pretest and post-test counselling and referral to a trained health provider
      for treatment of STI and the provision of services provided the framework for
      interventions in the groups following the survey. CONCLUSION: This represents an
      effective methodology for collecting risk behaviour and STI/HIV prevalence
      information concurrently and should be considered by countries expanding STI/HIV
      surveillance as part of UNAIDS second generation HIV surveillance.

PMID- 12238651
TI  - Prevalence of chlamydia and gonorrhoea among a population of men who have sex
      with men.
AB  - OBJECTIVES: Few data are available on the prevalence of sexually transmitted
      diseases (STDs) in men who have sex with men (MSM), making it difficult to
      develop STD screening guidelines for this population. The objective of the study
      was to determine the prevalence of urethral infections caused by Chlamydia
      trachomatis and Neisseria gonorrhoeae within a large, community based population
      of MSM, and to assess the feasibility of rectal screening in this population.
      METHODS: This was a cross sectional study of 566 MSM, who were predominantly
      middle aged, white, asymptomatic, and engaged in sex with multiple partners. All
      provided a urine sample to screen for chlamydial and gonorrhoea infections using
      a PCR assay; rectal screening was performed on 48 participants. RESULTS: Urethral
      C. trachomatis infections were detected in 1/566 participants (prevalence 0.2%,
      95% CI 0.004% to 1.0%), and rectal C. trachomatis infections were detected in
      2/48 men (prevalence 4.2%, 95% CI 0.5% to 14.2%). No gonorrhoea infections were
      detected, and none of the 117 HIV positive men had either infection. CONCLUSIONS:
      Chlamydial and gonorrhoea infections were uncommon in this sample of MSM, even
      among those with multiple sexual partners or HIV infection. These data call into
      question recommendations to screen all MSM based on their individual sexual
      behaviours or HIV. Additional data are needed on the prevalence of these
      infections in MSM from different settings.

PMID- 12238652
TI  - Detection of Chlamydia trachomatis in an Australian high school student
      population.
AB  - OBJECTIVE: To assess the prevalence of Chlamydia trachomatis infections among an
      Australian high school adolescent population. METHODS: Over a 4 year period, 14
      high schools were selected in which an infertility prevention programme targeting
      C. trachomatis was delivered to senior student populations. Coded first catch
      urine specimens were analysed by Amplicor PCR and infected students treated. Data
      retrospectively obtained from chlamydia screening programmes conducted among
      disadvantaged young people detached from formal education were also collated for
      comparison. RESULTS: Of a total student test population of 1174, 15 (1.3%; 95% CI
      0.7% to 2.1%) were diagnosed with C. trachomatis. Of 516 females and 658 males,
      12 (2.3%; 95% CI 1.1% to 4.1%) and 3 (0.5%; 95% CI 0.1% to 1.4%) were tested
      positive respectively. Data collated for three populations of disadvantaged youth
      returned at total of 89 C. trachomatis infections out of 560 people (15.9% 95%CI
      13.0-19.2%). CONCLUSION: The overall prevalence of C. trachomatis infection among
      this population of senior high school adolescents is low, and significantly
      differs from the higher chlamydia rates detected in disadvantaged adolescents
      detached from formal schooling (p<0.0001).

PMID- 12238653
TI  - Genital herpes: general practitioners' knowledge and opinions.
AB  - OBJECTIVES: To evaluate GPs' knowledge about genital herpes, especially recent
      information and to assess their attitudes towards serotesting. METHODS: GPs
      working in Coventry and the surrounding area were asked to complete an anonymous
      questionnaire. RESULTS: 70% of GPs (183 out of 261) responded to the
      questionnaire. Overall, 56% of the questions were answered correctly. 73% of
      participants knew that source partners in most transmission events are unaware of
      their infection and 77% were aware that patients shed the virus and transmit it
      even in the absence of clinical signs. As many as 43% did not know that the
      majority of infected individuals are unaware of their infection and 44% only knew
      that most transmission occurs during periods of asymptomatic shedding. Only 53%
      were aware that the proportion of genital herpes caused by HSV-1 is not
      decreasing. The majority (78%) supported the availability of its serotesting.
      CONCLUSIONS: This study demonstrates the lack of knowledge, among studied GPs, in
      some areas about genital herpes, especially recent information and indicates the
      need for more education about the condition. Most GPs in the study support the
      availability of genital herpes serotesting, although more studies need to be done
      before the wide availability of this testing.

PMID- 12238654
TI  - Seroprevalence of HSV-1 and HSV-2 infection in the general French population.
AB  - BACKGROUND: In spite of the large prevalence and growing incidence of herpes
      simplex infection (HSV-1 and HSV-2), relatively few large serological surveys are
      available worldwide and it is still difficult compare frequencies of HSV
      contaminations in various countries. We present the results of HERPIMAX, the
      first epidemiological inquiry on HSV prevalence in the general French population.
      METHODS: Of a cohort of 12,735 presumed healthy adult volunteers included in the
      prospective study SU.VI.MAX, designed to assess the relation between nutritional
      supplementations and degenerative diseases, HERPIMAX randomly selected 4412
      subjects (females 66.5%, males 33.5%). All serum samples were assessed for HSV-1
      and HSV-2 IgG antibodies with a HSV type specific, enzyme immunosorbent assay
      (EIA). Equivocal result were retested with another HSV type specific immunoblot
      assay combined with a type common HSV IgG EIA in order to give a definitive
      interpretation. RESULTS: The mean seroprevalence was 67% for HSV-1 and 17.2% for
      HSV-2. For HSV-2 the seroprevalence was higher in females (17.9%) compared with
      males (13.7%) (p<0.001). For both HSV types, there was no significant difference
      in prevalence as regards age distribution in males and females, whereas
      prevalence increased significantly with age in females for HSV-1. Univariate
      analysis showed a significant association between HSV-1 prevalence and education
      level in males and females (p<0.001) and between HSV-2 prevalence and marital
      status in both sexes (p<0.001). There were geographical disparities, with a
      higher HSV-2 prevalence in the south of France as well as in Paris. CONCLUSION:
      These results confirm a high prevalence of HSV infection in France. They are also
      in agreement with previous results of other survey carried out in other developed
      countries as regards higher prevalence of HSV-2 infection in women, the stability
      of seroprevalence for both HSV types after 35 years of age in females and 45
      years of age in males.

PMID- 12238655
TI  - Prevalence and risk factors of sexually transmitted infections and cervical
      neoplasia in women's health clinics in Nicaragua.
AB  - OBJECTIVES: To determine prevalence and risk factors of sexually transmitted
      infections (STIs), HIV, and cervical neoplasia in women attending women's health
      clinics in Nicaragua, and to assess the potential impact of screening for these
      diseases. METHODS: Consecutive women attending women's health clinics in
      different regions were interviewed and examined for STI, HIV, and cervical
      neoplasia. RESULTS: Whereas only 30.4% of the 1185 participating women attended
      the clinics because of STI related complaints, 77.0% reported symptoms after
      probing. Clinical cervicitis was diagnosed in 32.8%, Chlamydia trachomatis in
      4.1%, gonorrhoea in 0.4%, trichomoniasis in 10.2%. Antibodies for syphilis were
      found in 0.7%, for hepatitis B in 3.7%, and none were HIV seropositive. The STI
      prevalence was 21.8% in women offending with complaints, 17.3% in symptomatic
      women after probing, and 14.8% in asymptomatic women. Abnormal Papanicolaou (Pap)
      smears were found in 7.7%, with high risk human papilloma virus (HPV) types in
      almost 60%. Male promiscuity was associated with high grade squamous
      intraepithelial lesions (HSIL) and reported former screening was not shown to be
      protective. Young age and being employed were risk factors for C. trachomatis.
      CONCLUSION: Nearly one out of five women attending women's health clinics in
      Nicaragua had an STI, and one out of 13 a precancerous lesion of the cervix.
      These clinics provide an opportunity to improve the reproductive health of women
      by probing for STI symptoms, especially in young women, and by offering cervical
      screening to casual attendees. Of concern is the high rate of cervical lesions in
      women with a screening history, underlining the need for proper quality control.

PMID- 12238656
TI  - Epidemiology and natural history of ligase chain reaction detected chlamydial and
      gonococcal infections.
AB  - OBJECTIVES: Ligase chain reaction (LCR) technology has dramatically increased the
      sensitivity of tests for sexually transmitted infections (STIs). It is unknown
      whether low copy infections (LCR positive, culture negative) have any clinical
      consequences. We assessed the clinical significance of untreated low copy
      Chlamydia trachomatis and Neisseria gonorrhoeae infections in a cohort of
      sexually active women. METHODS: We studied a cohort of sexually active women
      followed at 6 month intervals for up to 3 years. Frozen urine specimens from 181
      women with negative cultures for C. trachomatis and N. gonorrhoeae who were 'high
      risk' (defined as being less than 40 years old at baseline, and having either
      Trichomonas vaginalis at baseline or a history of more than one sexual partner
      during the 12 months before baseline) were tested for C. trachomatis and N.
      gonorrhoeae by LCR (Abbott Laboratories, Abbott Park, IL, USA). The specimens
      from all visits for each person were pooled and LCR was performed on the pool.
      Laboratory results were linked to clinical information. We also tested all urine
      samples obtained from patients with a positive culture. RESULTS: 10 additional
      infections (nine C. trachomatis and one N. gonorrhoeae) were detected with LCR
      technique. None of the women with low copy infection had evidence of subsequent
      pelvic inflammatory disease or ectopic pregnancy. Pooling of urine samples
      resulted in a 47% decline in the number of tests performed. CONCLUSIONS:
      Additional STIs can be identified when using LCR. Pooling of urine specimens is a
      cost saving technique for C. trachomatis and N. gonorrhoeae testing.

PMID- 12238657
TI  - Oestrogen receptor transcripts associated with cervical human papillomavirus
      infection.
AB  - OBJECTIVE: Studies have been inconsistent in establishing sex steroids as a risk
      factor for human papillomavirus (HPV) infections. This study was designed to
      determine whether cervical oestrogen receptors (as measured by oestrogen receptor
      transcripts) at the cervix would be associated with cervical HPV infections.
      METHODS: In 175 women, ages 14-44, we tested for the presence of HPV DNA and
      oestrogen receptors transcripts at the cervix during routine pelvic examinations.
      All subjects completed a self administered questionnaire regarding sexual and
      menstrual histories. RESULTS: 40% of the women (n=70) tested positive for HPV at
      the cervix. Of those women testing positive for HPV, 99% had detectable levels of
      Oestrogen receptors transcripts (n=69/70). HPV cervical infections were
      independently associated with presence of Oestrogen receptors transcripts
      (OR=39.8, CI=4.4, 361.1) and greater numbers of sexual partners (OR=1.1, CI=1.01,
      1.18). CONCLUSION: Women who expressed higher levels of oestrogen receptors
      transcripts were significantly more likely to have cervical HPV infection. These
      results demonstrate that Oestrogen receptors may play an important part in
      cervical HPV infections.

PMID- 12238658
TI  - Risk factors for genital HPV DNA in men resemble those found in women: a study of
      male attendees at a Danish STD clinic.
AB  - OBJECTIVES: Genital infection with certain types of human papillomavirus (HPV) is
      the most important risk factor for cervical cancer. The male sexual partner is
      supposed to be the vector of the infection. However, the knowledge of risk
      factors for genital HPV DNA in men is limited. The objective of this paper is to
      study the risk factors for HPV infection in men and to compare them with those
      found in women, including the study of whether there are different risk profiles
      for oncogenic and non-oncogenic HPV types. METHODS: From a sexually transmitted
      diseases (STD) clinic in Denmark, 216 men were consecutively included. A personal
      interview was done and material for genital HPV DNA detection was obtained with
      swabs. HPV DNA was detected by polymerase chain reaction (PCR). Odds ratios (OR)
      for HPV as well as for oncogenic and non-oncogenic types separately were computed
      with a 95% confidence interval (CI) by means of unconditional multiple logistic
      regresssion. RESULTS: The most important predictors of any HPV were lifetime
      number of sex partners (OR = 4.3; 95% CI 1.4 to 13.1 for 25-39 v 1-9 partners),
      young age, and being uncircumcised. The most important risk factor for oncogenic
      HPV types was lifetime number of partners, whereas number of partners in the past
      year and ever having genital warts were risk factors for the non-oncogenic HPV
      types. Young age predicted risk of both oncogenic and non-oncogenic HPV types.
      CONCLUSIONS: Most risk factors for HPV DNA detection in men resemble those found
      in women. As in women, the risk factor profile for the oncogenic HPV types was
      different from that of the non-oncogenic HPV types.

PMID- 12238659
TI  - The evolution of sexually transmitted infections in the Ukraine.
AB  - OBJECTIVES: To evaluate trends in the national and regional reporting of
      syphilis, gonorrhoea, chlamydia, genital herpes, trichomoniasis, and HIV in
      Ukraine. METHODS: Annual notification rates of infection per 10(5) population in
      three regions of Ukraine--Donetsk, Mikolaiv, Chernivtsi--and also among children,
      adolescents, and pregnant women were used as indicators for the spread of
      sexually transmitted infections (STIs) in the Ukraine from 1994 to 2000. The
      estimates were based on a review of medical literature, reported data from STD
      clinics, and local epidemiological surveys. An analysis of the trends was made.
      RESULTS: The notification rate of trichomoniasis rose from 284.3 in 1997 to 330.8
      in 2000. The same for syphilis was 68.7 per 100,000 population in 1994 peaked in
      1996 with 150.9 falling to 91.5 in 2000. The reported incidence of gonorrhoea has
      been falling recently to 52.7/10(5) in 2000 (a 104.6% decrease since 1994).
      Chlamydia notification rates, however, rose 2.4-fold between 1995 and 2000
      (16.1/10(5) to 54.2/10(5)). In the same period there was a 218% increase the
      reported incidence of genital herpes. STIs are more common in the eastern
      industrial regions. In the period 1994-7 there was a dramatic 179-fold increase
      in the prevalence of HIV/AIDS which has plateaued in subsequent years. By January
      2001 a total of 36,600 cases of HIV infection (including 2040 people with AIDS)
      have been reported. The proportion of HIV acquired through injecting drug use is
      falling (72.7% in 1997 to 54.2% in 2000) in relation to that acquired through
      sexual contact. CONCLUSIONS: STIs and HIV are a common cause of morbidity in
      Ukraine.

PMID- 12238660
TI  - The practice of STI treatment among chemists and druggists in Pokhara, Nepal.

PMID- 12238661
TI  - Hepatitis, syphilis, and HIV sentinel surveillance in Mongolia 1999-2000.

PMID- 12238662
TI  - Congenital syphilis--missed opportunities for prenatal intervention.

PMID- 12238663
TI  - Condom access does not ensure condom use: you've got to be putting me on.

PMID- 12238664
TI  - Resolution of the recent performance problem of Abbott LCx Chlamydia trachomatis
      assay. Issues of repeat testing for confirmation of chlamydial infection.

PMID- 12238665
TI  - It is axiomatic for those engaged in medical practice to assume that publication
      is a priori, a good thing.

PMID- 12238666
TI  - A century of citation classics in otolaryngology-head and neck Surgery journals.
AB  - The Science Citation Index (SCI) was introduced primarily as a method of
      information retrieval but has also been used an objective measure of the quality
      of an article. Citation classics have been described as papers that have been
      cited 100 times or more. The aim of this study was to identify the articles
      published during the 20th century in otolaryngology-head and neck surgery
      journals that have achieved classic citation status and to present an analysis of
      this data. Using a database provided by the Institute of Scientific Information
      (Philadelphia, PA), an assessment was performed of all articles cited 100 or more
      times in one of the 28 clinical otolaryngology-head and neck journals indexed by
      the annual Journal Citation Reports. The data were based on citation counts using
      the 1900 through 1999 Science Citation Index. Institutions located in 10
      different countries produced 80 noteworthy articles. The most-cited paper
      achieved a citation score of 406 and there were 11 articles cited on more than
      200 occasions. All of the articles were published in eight journals. The earliest
      identified publication was in 1933 and the most recent was published in 1993.
      Twenty authors were involved in two articles and four authors were associated
      with three classic citations. This paper confirms that analysing citation
      classics reveals a partial insight into advances and historical developments in
      the specialty during the last century.

PMID- 12238667
TI  - A new technique (the NOW test) for the detection of Streptococcus pneumoniae in
      the effusions of otitis media.
AB  - The presence of Streptococcus pneumoniae in chronic otitis media was determined
      with a new antigen detection kit, the NOW test. The NOW test was originally
      designed as a urinary antigen test but was adapted to middle-ear effusions for
      the present study. Middle-ear effusions from 52 children were studied.
      Streptococcus pneumoniae was cultured from 10 per cent of the effusions. The NOW
      test was positive in 23 per cent of the effusions, 80 per cent of culture
      positive and 17 per cent of culture negative effusions. The NOW test proved to be
      rapid, simple, reliable and relatively inexpensive for the detection of
      pneumococcal antigen in the middle-ear effusions. This test may prove valuable
      for the management of children with acute otitis media who undergo
      tympanocentesis.

PMID- 12238668
TI  - Effect of KTP laser on implants used in middle-ear surgery.
AB  - The present study is intended to explore the effects of the KTP laser on various
      types of implant, used in middle-ear surgery. A laboratory study was undertaken
      to evaluate the interaction between the KTP laser (KTP-532 Orion Laser,
      Laserscope, UK) and individual middle-ear implants. A variety of middle-ear
      implants were used: a silicone sheet, Teflon, hydroxylapatite, ionomeric cement,
      gold and titanium prostheses as well as gelfoam. Following exposure to the laser,
      these implants were studied by direct inspection using an operating microscope.
      The KTP laser induced no detectable alteration in any of the implants when they
      were clean and dry. However, in the presence of fresh blood, under the influence
      of the energy of the absorbed laser, the silicone burnt and melted and the Teflon
      piston was vaporized. Likewise, a few tiny holes appeared on the surface of the
      ionomeric implant and then the prosthesis deformed. The hydroxylapatite implant
      broke into two pieces. However, no detectable alteration could be observed on
      gold or titanium pistons, even in the presence of blood. The authors conclude,
      that in the presence of blood, interaction between the KTP laser and both
      silicone and hydroxylapatite implants needs to be avoided. Teflon prostheses can
      be cautiously vaporized. Gold and titanium prostheses were unaffected by laser
      even in the presence of blood.

PMID- 12238669
TI  - Clarion 1.2 standard electrode array with partial space-filling positioner:
      radiological and histological evaluation in human temporal bones.
AB  - The purpose of this study was to evaluate whether use of a positioner for
      situating the Clarion 1.29 standard electrode array in close proximity to the
      modiolus, causes damage to fine intra-cochlear structures, and to provide a
      comparison with results obtained for insertions of the array performed without a
      positioner. The study was performed in seven freshly frozen human temporal bones.
      Electrode location and intra-cochlear trauma was analysed using cross-sectional
      imaging and histological analysis. Insertion of the Clarion array did not reveal
      major trauma. The devices inserted with the positioner showed a consistently
      closer location of the electron array towards the modiolus, however, insertion
      resulted in significant displacement of both the electrode array and the
      positioner resulting in severe destruction of the basilar membrane and osseous
      spiral lamina along the length of the basal and middle turns. The devices
      inserted with the positioner resulted in major trauma to the basilar membrane and
      osseous spiral lamina. Therefore, systematic safety studies in larger samples of
      human temporal bones should be performed and the results carefully evaluated
      before implantation can be recommended unreservedly.

PMID- 12238670
TI  - Dehiscence of the bony roof of the superior semicircular canal in the middle
      cranial fossa.
AB  - Spontaneous dehiscence of the superior semicircular canal (SSC) in the middle
      cranial fossa is rare and may cause clinical problems. This dehiscence was
      investigated in cadaveric and dried temporal bone specimens. One cadaveric
      specimen showed a spontaneous defect: the dehiscence was a symmetrical, elongated
      ellipse with smooth margins. Four of 244 dry bone specimens showed bony defects
      in the roof of the SSC, however, only one specimen was thought to have a
      spontaneous defect. Based on computer-simulation models, we hypothesized that
      spontaneous defects of the SSC may arise during the fetal period. Although rare,
      this defect may cause problems in middle cranial fossa surgery and may relate to
      certain vertiginous disorders.

PMID- 12238671
TI  - Skin reactivity to vasomotor agents in non-eosinophilic and eosinophilic non
      allergic rhinitis.
AB  - The aim of this prospective study was to examine skin reactivity to four
      vasomotor agents and to determine whether non-eosinophilic rhinitis patients
      differ from patients with eosinophilic rhinitis. Nasal cytology enabled us to
      classify 74 rhinitis patients into a non-eosinophilic (n = 63) and an
      eosinophilic group (n = 11). Skin reactivity to intradermal tests with
      papaverine, metacholine, histamine and compound 48/80 was measured. No
      significant difference for papaverine, metacholine, histamine and compound 48/80,
      singly, was found between the non-eosinophilic and eosinophilic group. The
      frequency of the total pathological skin reactivity to vasomotor agents, singly
      and in combinations, was greater in the eosinophilic (91 per cent) then in the
      non-eosinophilic group (78 per cent) but intergroup difference was not
      significant. These findings suggest that pathologic skin reactivity to vasomotor
      agents is a feature of non-eosinophilic as well as eosinophilic non-allergic
      rhinitis patients and indicate that no difference is noticed in the skin
      reactivity between these groups.

PMID- 12238672
TI  - Pharyngeal cancer prevention: evidence from a case--control study involving 232
      consecutive patients.
AB  - The aim of this study was to determine risk factors for pharyngeal cancer and to
      propose 10 result-based preventive measures. It was a case-control study
      conducted in Madrid, Spain, with 232 consecutive patients diagnosed between
      January 1 1990 and December 31, 1995, sex- and age-matched with 232 control
      individuals with no oncological disease or history. By means of an interviewer
      administered questionnaire, seven different epidemiological areas were surveyed,
      namely: (1) sociodemographic variables, (2) familial all-site cancer history, (3)
      medical history, (4) lifestyle (habits), (5) diet, (6) occupational exposure, and
      (7) non-occupational exposure. Of the great number of factors within each
      epidemiological area, the following were found to be risk factors after
      adjustment for tobacco smoking and alcoholic beverage drinking: (1) tobacco
      smoking, (2) alcoholic beverage drinking, (3) low and low-middle socioeconomic
      background, (4) low educational level, (5) rural milieu, (6) working, or having
      worked, as a manual worker in agriculture, (7) working, or having worked as a
      manual worker in building industry, (8) having an upper aerodigestive tract
      cancer familial history, (9) having a medical history of alcholism, low
      weight/malnutrition, gastroesophageal reflux or chronic obstructive
      bronchopneumonia, (10) low dietary intake of fruit, fruit juice, uncooked
      vegetables, dietary fibre-containing foods, fish and milk and dairy products,
      (11) high dietary intake of meat and fried foods, (12) deficient oral and dental
      hygiene, (13) abuse of black coffee, (14) abuse of 'carajillo' (a typical Spanish
      drink composed of black coffee and flambeed brandy), (15) occupational exposure
      to pesticides, solvents and dust of different origins. On the basis of our
      results and those reported by other authors, we put forward 10 measures for the
      prevention of pharyngeal cancer. However, due to the small size of the
      nasopharyngeal cancer subsample (n = 35, 15.08 per cent), our results as well as
      the preventive measures are to considered as referring uniquely to oropharyngeal
      and hypopharyngeal cancers. In addition, from descriptive statistical data
      inspection one can conclude that nasopharyngeal cancer is likely to bear risk
      factors different from those for oropharyngeal and hypopharyngeal cancers, thus
      nasopharyngeal cancer warrants specific epidemiological investigation with a
      sufficiently large patient sample.

PMID- 12238673
TI  - Paediatric tracheostomy: Sheffield experience 1979-1999.
AB  - We have reviewed our experience of tracheostomy in children over the past 20
      years at Sheffield Children's Hospital. One hundred and forty-eight
      tracheostomies were performed in 143 children aged one day to 13 years old
      (average 27 months). Sixty-five per cent of patients were < one year old. The
      indications for tracheostomy were upper airways' obstruction in 72 per cent, and
      assisted ventilation/ bronchopulmonary toilet in 28 per cent. The commonest
      single reason was acquired subglottic stenosis (SGS) in infants, accounting for
      25 per cent of tracheostomies (36/143). The complication rate of tracheostomy was
      46 per cent, most commonly granulation tissue formation. There were four deaths
      directly due to the tracheostomy: two accidental decannulations and two
      obstructions. Eighty-nine children were decannulated under our care. The average
      time until decannulation was 25 months.

PMID- 12238674
TI  - Effect of Ringer-Lactate and isotonic saline solutions on mucociliary clearance
      of tracheal epithelium: an experimental study in rats.
AB  - Isotonic saline solution is frequently used in nasal and tracheal lavage. In a
      previous clinical study, it was found that Ringer-Lactate solution, as a nasal
      lavage, was better for mucociliary clearance function than isotonic saline
      solution after nasal septal surgery. In this experimental study, the effects of
      Ringer-Lactate and isotonic saline solutions on mucociliary clearance of healthy
      rat tracheal epithelium were investigated by measuring the transport of carbon
      particles. We found that tracheal segments that were irrigated with Ringer
      Lactate had better mucociliary transport than those irrigated with isotonic
      saline (p = 0.035).

PMID- 12238675
TI  - Nasal septal clip (Cigdem clip).
AB  - We report the use of a nasal septal clip. We believe that this instrument is more
      easily inserted and removed when compared with the classical nasal packs.

PMID- 12238676
TI  - Group-A streptococcal meningitis in an adult, secondary to purulent otitis media.
AB  - Group A streptococcal meningitis is rarely encountered today, although group A
      streptococcal severe infections are on the increase. We present here a case of an
      adult male with bacterial meningitis as a complication of otitis media induced by
      Group A Streptococcus. The approach to diagnosis and treatment considerations are
      discussed.

PMID- 12238677
TI  - Nasal septal abscess: an unusual complication of acute spheno-ethmoiditis.
AB  - Nasal septal abscess complicating acute sinusitis is rare. There have been very
      few reports in the literature of this condition. We present a 12-year old-male
      with a nasal septal abscess complicating acute pansinusitis.

PMID- 12238678
TI  - Spontaneous CSF rhinorrhoea from separate defects of the anterior and middle
      cranial fossa.
AB  - Multiple congenital dehiscence of the skull base is rare and can give rise to
      spontaneous CSF rhinorrhoea. A search of the world literature revealed only five
      reports of CSF leak with more than one concomitant skull base defect. When
      treating a patient with spontaneous CSF rhinorrhoea the possibility of its
      originating from the middle ear and eustachian tube should be considered. An
      intrathecal injection of fluorescein is useful in establishing the site of a CSF
      leak especially when a computed tomography scan (CT) or magnetic resonance image
      (MRI) has not localized the site. We discuss a case of a 72-year-old lady
      presenting with CSF rhinorrhoea, who had an anterior skull base defect localized
      with the help of intrathecal fluorescein and repaired surgically. Subsequent to
      this she had a further episode of CSF rhinorrhoea that originated from a middle
      ear meningocele that was then repaired.

PMID- 12238679
TI  - Penetrating injury of the cheek requiring skull base exploration.
AB  - We report a case of a very unusual penetrating injury of the middle third of the
      face. The patient was involved in a road traffic accident, and the indicator
      control lever became impaled in his right cheek. There was contralateral orbital
      damage resulting in loss of sight. The cribriform plate was breached and a
      pneumoencephalocele ensued. We discuss the modern management of such injuries
      including injury assessment. We emphasize the importance of crash scene
      information gathering and analysis of injury mechanisms. Facial injury zonal
      classification and imaging are reviewed in the context of the case. We discuss
      the reasons that led us to treat this patient via the subcranial approach.

PMID- 12238680
TI  - Schwannomatosis in a child--or early neurofibromatosis type 2.
AB  - A case of multiple cervical schwannomas in a five-year-old boy, without other
      evidence of neurofibromatosis type 2, is described. Schwannomatosis is a disorder
      characterized by the presence of multiple schwannomas in the absence of
      neurofibromatosis type 2 that has only been recognized in the last 15 years. The
      clinical and genetic features of neurofibromatosis types 1 and 2 and
      schwannomatosis are compared and contrasted. This patient with possible
      schwannomatosis is presented to illustrate the potential pitfalls of making this
      diagnosis in the paediatric age group and to increase awareness of the debate on
      whether this is a distinct entity or a form fruste of neurofibromatosis type 2.

PMID- 12238681
TI  - Masked pseudomonal skull base osteomyelitis presenting with a bilateral Xth
      cranial nerve palsy.
AB  - Skull base osteomyelitis classically presents as a complication of severe
      external otitis, middle ear, mastoid or sinus infection and can lead to multiple
      lower cranial nerve palsies when the jugular foramen is involved as a consequence
      of widespread involvement of the skull base. Bilateral skull base osteomyelitis
      is a recognized phenomenon, but has not previously been reported secondary to
      pseudomonal infection in the absence of a clinically obvious focus of infection.
      We report the case of a 77-year-old diabetic patient who presented with dysphonia
      and dysphagia and had a bilateral Xth cranial nerve palsy. No focus of infection
      was evident on presentation. Subsequent radiological investigation confirmed the
      diagnosis of bilateral skull base osteomyelitis.

PMID- 12238682
TI  - Detachable forceps for flexible fibre-optic surgery: a new technique for
      phonosurgery in cases where rigid laryngoscopy is contraindicated.
AB  - In phonosurgery, in cases where it is not possible to use a rigid laryngoscope, a
      flexible fibrescope with laryngeal-mask ventilation may be used. In flexible
      fibreoptic surgery, the forceps are normally inserted through a small channel in
      the fibrescope. Since only a small forceps tip can pass through this channel, a
      limited range of forceps has been available for use in fibrescope procedures. We
      have developed a new type of forceps for flexible fibre-optic surgery that allows
      this size limitation to be overcome. The new forceps is made up of two parts: (i)
      the forceps tip and its control wire assembly, and (ii) a detachable handle. A
      wide range of forceps can be used, including those with tips larger than the
      biopsy channel. We report a case that was treated with this new technique.

PMID- 12238683
TI  - Tracheo-innominate artery fistula: a rare complication in a laryngectomized
      patient.
AB  - A tracheo-innominate artery fistula is an uncommon but frequently fatal
      complication of tracheostomy. Rarely, it can also occur in laryngectomized
      patients. We report a post-laryngectomy, post-radiotherapy patient using a metal
      tracheostomy tube, who developed a tracheo-innominate artery fistula about two
      months after radiotherapy. To our knowledge this is only the second reported case
      in a laryngectomized patient. The computed tomography (CT) angiography findings
      helped confirm the diagnosis and the patient was successfully managed by surgical
      exploration and ligation of the innominate artery. Coagulase negative
      Staphylococcus aureus was cultured from a tracheal swab. The clinical features,
      CT angiography findings, management protocols and possible aetiological factors
      are discussed.

PMID- 12238684
TI  - Rhinologic changes in Wegener's granulomatosis.
AB  - Twenty-eight patients with a clinical diagnosis of sinonasal Wegener's
      granulomatosis were referred for imaging during the period 1990-2001. Of these,
      10 had clinical symptoms and signs confined to the nose and sinuses and 18 had
      classical systemic Wegener's. The computed tomography (CT) and magnetic resonance
      (MRI) scans of the series were reviewed by a panel of one otolaryngologist and
      two radiologists. From the total of 28 patients, 85.7 per cent showed non
      specific mucosal thickening in the nasal cavity or paranasal sinuses, 75 per cent
      showed evidence of bone destruction, and 50 per cent new bone formation in the
      walls of the sinus cavities. In addition the orbit was affected in 30 per cent of
      patients. The diagnosis of systemic Wegener's granulomatosis is made clinically
      but the condition may present characteristic features on imaging by CT and MRI.
      In a patient without a history of previous sinonasal surgery, a combination of
      bone destruction and new bone formation on CT is virtually diagnostic of
      Wegener's especially when accompanied on MRI by a fat signal from the sclerotic
      sinus wall. These changes are important diagnostically in localized sinonasal
      Wegener's granulomatosis where the clinical diagnosis may be uncertain and the
      cANCA test can be negative.

PMID- 12238685
TI  - Bruxism and cold sensitivity.

PMID- 12238686
TI  - Controlled orthodontic extrusion to create gingival papilla: a case report.
AB  - Prosthetic dental restorations alone do not produce esthetics. They must be in
      harmony with the surrounding gingiva, especially the gingival papilla. This case
      report describes the enhancement of the gingival papilla between an implant
      replacing the maxillary left central incisor and a provisional crown on the
      maxillary left lateral incisor. Esthetic harmony was disrupted by the absence of
      an interproximal papilla. First, provisional crowns on the implant and adjacent
      tooth were used in an attempt to remodel the interproximal gingival tissue, but
      the esthetic result was not satisfactory. The second attempt involved orthodontic
      extrusion of the lateral incisor in an incisal direction. The gingival tissue
      migrated incisally, thus restoring the deficient papilla and establishing
      restorative and gingival harmony. Both the implant and the lateral incisor were
      restored with ceramic crowns.

PMID- 12238687
TI  - Comprehensive treatment concept in a young adult patient with severe periodontal
      disease: a case report.
AB  - This case report describes the comprehensive treatment of generalized, advanced
      periodontal disease in a young patient. In view of the necessary reconstruction,
      the extensive destruction of the periodontal tissues required a systematic
      approach to determine the possibilities and the expectations of the patient. The
      subsequent oral rehabilitation was accomplished with fixed prosthodontics. In the
      mandible, strategically important anchor teeth were replaced with implants,
      allowing smaller units to be inserted. The long-term treatment result, however,
      can only be ensured with the full cooperation of the patient and consistent
      periodontal maintenance care.

PMID- 12238688
TI  - Clinical comparison of a multistranded wire and a direct-bonded polyethylene
      ribbon-reinforced resin composite used for lingual retention.
AB  - OBJECTIVE: The reliability of posttreatment canine-to-canine retention with resin
      composite retainers reinforced with plasma-treated woven polyethylene ribbons was
      compared to the reliability of directly bonded, multistranded wire retainers.
      METHOD AND MATERIALS: This prospective study was based on an assessment of 20
      consecutive patients (eight women and 12 men with a mean age of 22.4 years) who
      required a fixed canine-to-canine retainer after undergoing orthodontic
      treatment. The type of retainer used was randomized for each patient. A follow-up
      examination was carried out once every 3 months. The length of time the retainers
      stayed in place without resin fracture or loosening from the teeth at one or more
      points was evaluated. The study's endpoint was 24 months after the retainer had
      been bonded. RESULTS: The ribbon-reinforced retainer remained in place for an
      average of 11.5 months, and the multistranded wire for a mean of 23.6 months. The
      difference was statistically significant. CONCLUSION: In terms of reliability for
      permanently fixed orthodontic retention from canine to canine, the direct-bonded
      multistranded wire is superior to the plasma-treated polyethylene woven ribbon
      and resin retainer.

PMID- 12238689
TI  - Treatment of a juvenile patient with a maxillary all-ceramic resin-bonded fixed
      partial denture: a case report.
AB  - Treatment of juvenile patients with a missing maxillary incisor is difficult,
      because an implant cannot be placed until growth is completed. The other
      minimally invasive alternatives are also problematic: Removable dentures are
      rarely accepted by juvenile patients, and the conventional resin-bonded fixed
      partial denture often provides a poor esthetic result because the metal retainer
      causes the abutment teeth to lose their natural translucency and to become
      grayish. Moreover, the alveolar ridge defect makes it easy to identify the
      prosthesis in the pontic area. The present case report describes the prosthetic
      treatment of a juvenile patient who had lost a maxillary incisor to trauma. To
      avoid the disadvantages of conventional therapies, subepithelial connective
      tissue was grafted to reshape the alveolar ridge. The space was closed with an
      all-ceramic resin-bonded fixed partial denture.

PMID- 12238690
TI  - Resistance to maxillary premolar fractures after restoration of class II
      preparations with resin composite or ceromer.
AB  - OBJECTIVE: The aim of this study was to evaluate the resistance to fracture of
      intact and restored human maxillary premolars. METHOD AND MATERIALS: Thirty
      noncarious human maxillary premolars, divided into three groups of 10, were
      submitted to mechanical tests to evaluate their resistance to fracture. Group 1
      consisted of intact teeth. Teeth in group 2 received mesio-occlusodistal cavity
      preparations and were restored with direct resin composite restorations. Teeth in
      group 3 received mesio-occlusodistal cavity preparations and were restored with
      ceromer inlays placed with the indirect technique. After restoration, teeth were
      stored at 37 degrees C for 24 hours and then thermocycled for 500 cycles at
      temperatures of 5 degrees C and 55 degrees C. RESULTS: Statistical analysis
      revealed that group 3 (178.765 kgf) had a significantly greater maximum rupture
      load than did group 1 (120.040 kgf). There was no statistically significant
      difference between groups 1 and 2 or between groups 2 and 3. CONCLUSION: Class II
      cavity preparations restored with indirect ceromer inlays offered greater
      resistance to fracture than did intact teeth. The fracture resistance of teeth
      restored with resin composite was not significantly different from that of either
      the ceromer or intact teeth.

PMID- 12238691
TI  - Effect of adhesives on bond strength of porcelain veneer to base metal alloy.
AB  - OBJECTIVE: The purpose of this in vitro study was to evaluate the bond strength
      of porcelain veneer to base metal alloy using different adhesive systems. METHOD
      AND MATERIALS: Eighty cylindrical models were cast in a nickel-chromium-beryllium
      base metal alloy. After they were mounted in self-cured acrylic resin, the
      surfaces of the specimens were air abraded. Specimens were divided into four
      groups of 20. Control porcelain disks were baked on the base metal. For the
      experimental groups, 60 porcelain disks were made. After 50-microm aluminum oxide
      sandblasting, a silane coupling agent was applied to the surface of the
      porcelain. The experimental groups were based on the type of adhesive used to
      bond porcelain to metal: Scotchbond Multipurpose and Duo Cement; One Coat Bond
      and Duo Cement; or Panavia 21 Ex. After 500 thermal cycles, the bonded porcelain
      specimens were placed under a continuous shear load of 2 mm/min until fracture
      occurred. RESULTS: Mean values for bond strength were 25.39 (control), 19.10
      (Panavia 21 Ex), 15.81 (Scotchbond Multipurpose), and 13.69 MPa (One Coat Bond).
      Statistically significant differences in bond strength were noted between the
      control group and all the experimental groups. A statistically significant
      difference was observed between Panavia 21 Ex specimens and One Coat Bond
      specimens. CONCLUSION: Panavia 21 Ex provided an effective bond strength between
      a porcelain veneer and a base metal alloy, the closest of all the experimental
      groups to that of the control group.

PMID- 12238692
TI  - Histomorphometric analysis of dentinal bridge formation and pulpal inflammation.
AB  - OBJECTIVE: The purpose of this study was to evaluate pulpal responses to the use
      of four resin composite materials as direct pulp capping agents. The importance
      and effects of individual pulp capping variables are not well understood;
      consequently histomorphometric analysis was used to analyze these variables.
      METHOD AND MATERIALS: Two hundred fifty standardized pulp-exposed cavities were
      prepared in nonhuman primate teeth. Exposed pulps were capped with calcium
      hydroxide and multistep and self-etching primer resin composites. Teeth were
      collected from 3 to 60 days to observe pulpal reactions. Following perfusion
      fixation, tissues were demineralized, sectioned, stained, and
      histomorphometrically measured. Bridge area, diameter of pulpal exposure, and
      cavity floor width were measured. Tunnel defects, operative debris, and pulpal
      inflammation were graded according to defined criteria. RESULTS: The variables
      correlated to dentinal bridge area were, in decreasing order of significance,
      time elapsed since exposure, diameter of pulpal exposure, pulp capping material,
      and tunnel defects. The variables correlated to pulpal inflammation were the type
      and curing of pulp capping material. Other variables were not statistically
      significant. CONCLUSION: Pulp capping with resin composite materials provided
      acceptable pulpal inflammatory and dentinal bridge repair responses, comparable
      with those of calcium hydroxide. Although resin composites are promising as
      direct pulp capping agents, further investigations are required to optimize their
      application protocols to reduce the penetration of potentially cytotoxic monomers
      into pulpal tissue.

PMID- 12238693
TI  - Retrieval of a foreign object from the palatal root canal of a permanent
      maxillary first molar: A case report.
AB  - A 12-year-old boy presented with a fractured sewing needle within the palatal
      root canal of a nonvital permanent maxillary first molar. The patient admitted
      that he had often placed a sewing needle in the tooth to relieve discomfort
      associated with it. A minimal amount of tooth structure was removed around the
      foreign object to facilitate access for K-type files. Under copious irrigation,
      the files were worked around the object to loosen it. The fractured needle was
      removed with a tweezers that had long, narrow beaks. Use of this simple technique
      allowed the object to be removed from the root canal with minimal damage to
      internal tooth structure.

PMID- 12238694
TI  - The surgical removal of mandibular third molars: a study in decision making.
AB  - OBJECTIVE: The aim of this study was to investigate and analyze the angulation of
      and the various indications for removal of mandibular third molars in Jordanians
      as a representative Arab sample. METHOD AND MATERIALS: The data included in this
      retrospective study were obtained from the clinical and radiographic records of
      1,282 patients undergoing mandibular third molar surgery during a 5-year period
      from 1994 to 1999. The indications for removal of the mandibular third molars
      were classified in accordance with age and gender. The angular position of
      mandibular third molars was registered. RESULTS: A total of 2,252 mandibular
      third molars were removed from 740 male patients (57.7%) and 542 female patients
      (42.3%) aged 14 to 67 years. Pericoronitis was the most common indication for
      surgery, affecting 1,055 teeth (46.8%). Caries was observed in 519 third molars
      (23.0%). The vertical angular position was most commonly found (1,383 teeth;
      61.4%) followed by the mesioangular position (407 teeth; 18.1%). CONCLUSION: The
      results obtained in this study are similar to those reported in earlier studies
      carried out elsewhere, although the incidence of periodontitis among Jordanians
      was significantly higher and occurred in older patients, and prophylactic removal
      was performed less frequently than has been reported in other countries.

PMID- 12238695
TI  - Diagnosis and dental treatment of a young adult patient with gastroesophageal
      reflux: a case report with 2-year follow-up.
AB  - A young adult who complained of extreme dentin sensitivity to tactile and thermal
      stimuli exhibited severe, generalized tooth erosion and an associated
      parafunctional habit. The diagnosis of the underlying general disease and
      treatment of its dental sequelae are presented, together with a 2-year follow up.
      Patients who are suspected of having gastroesophageal reflux should be referred
      to a gastroenterologist or other health professionals to ensure early diagnosis
      and treatment of the underlying disorder, thus minimizing the destruction of the
      patient's dentition and improving the patient's general health. Dental treatment
      should be adjusted to fit the characteristics of each case.

PMID- 12238697
TI  - Digital clubbing.

PMID- 12238696
TI  - Composite shrinkage revisited.

PMID- 12238698
TI  - Predictors of intention to promote family planning: a survey of Protestant
      seminarians in the United States.
AB  - The purpose of this study was to examine Protestant seminary students' intention
      to promote family planning. Intention to promote family planning and its
      predictors were examined by testing a conceptual model based on the theory of
      planned behavior and social cognitive theory. A nonrepresentative sample of 635
      seminarians (90.5% Anglo; 66.5% male) from 10 theological schools in the United
      States completed a mailed survey. Students were classified according to their
      religious beliefs as conservative (61.9%) and nonconservative (38.1%), and group
      differences in intention (and its correlates) were examined. Structural equation
      modeling was used to assess relationships among attitudes toward sexuality,
      attitudes toward family planning, subjective norms, knowledge, self-efficacy, and
      intention for both conservative and nonconservative students. Results indicated
      that the relationships among predictors of intention were essentially similar for
      both conservative and nonconservative seminarians, with attitudes and self
      efficacy for promoting family planning exhibiting the strongest direct effects on
      intention.

PMID- 12238699
TI  - Perspectives of pregnant and postpartum latino women on diabetes, physical
      activity, and health.
AB  - Impaired glucose tolerance and diabetes are prevalent among Latino women of
      childbearing age. Physical activity during and after pregnancy may contribute to
      weight control and improved metabolic status, but recommended activities may not
      be perceived as appropriate or feasible. To plan realistic and acceptable
      interventions, pregnant and postpartum Latino women in Detroit met in a focus
      group series to discuss their beliefs about diabetes and factors influencing
      their participation in regular physical activity during pregnancy and postpartum.
      Women believed that diabetes was primarily related to heredity and diet but not
      to physical activity. Exercise was believed to reduce stress and improve general
      health. Women suggested an organized group intervention, in a respected location,
      that offered safe physical activities within the context of a variety of
      activities for women and children. This strategy reduced concerns about safety
      and social acceptability while addressing their primary interest in social
      support.

PMID- 12238700
TI  - Infant birth weight as a measure of harm reduction during smoking cessation
      trials in pregnancy.
AB  - During pregnancy, a reduction of 50% or more of a biochemical measure of smoking,
      among continuing smokers, has been proposed by Windsor and colleagues as a new
      behavioral indicator of harm reduction because it was accompanied by greater
      infant birth weight compared with that of infants of smokers with lesser
      reductions. The purpose of the authors' study was to replicate these
      observations. During a trial of smoking cessation during pregnancy, data on
      cigarettes per day, urinary cotinine. and infant birth weight were obtained from
      240 women. There were no significant differences in average birth weight between
      infants of women whocontinued to smoke but reduced their cigarette consumption by
      50% or more and infants of women with lesser reductions. These results indicate
      that this birth weight comparison does not provide a valid estimate of the harm
      reduction associated with a reduction of 50% or more in cigarette consumption
      during pregnancy.

PMID- 12238701
TI  - Integrating quantitative and qualitative methods to assess the impact of child
      survival programs in developing countries: the case of a program evaluation in
      Ceara, Northeast Brazil.
AB  - In evaluating public health programs, the tradition has been to design
      quantitative approaches, relying on epidemiological and statistical techniques to
      determine if and to what extent a program has an effect on a predetermined
      targeted population. More recently, however, qualitative methods such as rapid
      ethnographic assessments and focus groups have been implemented more frequently.
      This article describes an outcome evaluation of a community health workers
      program that integrated quantitative and qualitative methods to assess the impact
      of child survival interventions in reducing infant mortality and inadequate
      weight gain in children among municipalities in the state of Ceara, Northeast
      Brazil. By using multiple methods that combine quantitative and qualitative
      components, researchers can broaden their understanding of complex public health
      issues and direct use of data for decision making.

PMID- 12238702
TI  - Predictors of participation in two different smoking cessation interventions at
      school.
AB  - Multinomial logistic regression was used to identify demographic and psychosocial
      characteristics of Belgian secondary school students (N = 493), aged 16 to 20, to
      predict which students choose to participate in a group-based smoking cessation
      program (five 1-hour weekly sessions), requested self-help quitting material, or
      did neither (comparison group). The participation rate was 29% for requesting
      self-help material and 21% for participation in the group program. The analysis
      indicated that students choosing to participate in the smoking cessation program
      were more likely to be in the 12th grade, technical students, and daily smokers.
      They were more likely to believe that quitting would be difficult and reported
      stronger intentions to quit now and to participate in the group program. Students
      requesting the self-help materials were less likely to be general students but
      more likely to see the benefits of quitting; they also reported stronger
      intentions to participate in the group program.

PMID- 12238703
TI  - The effect of maternal depressive symptomatology on maternal behaviors associated
      with child health.
AB  - National prevalence rates for depression among women are twofold compared with
      those of men, with women of childbearing age at greatest risk. Maternal
      depression not only negatively affects the health of the mother but may also
      influence the health and development of her offspring. This study examined the
      relationship between maternal depression and its influence on certain maternal
      behaviors associated with child health. A nationally representative, longitudinal
      data set with information on demographic, behavioral, and health care variables
      obtained from women in 1988 and 1991 was used. The results from logistic
      regression modeling indicate that maternal depression is associated with maternal
      behaviors (i.e., an increased likelihood of engagement in smoking, in not
      administering vitamins to a child, and not restraining children in appropriate
      car seats). Moreover, race differentials were found among these relationships.
      The implications of these results suggest the need to screen for depression among
      mothers of young children.

PMID- 12238704
TI  - Dissemination of an efficacious antenatal smoking cessation program in public
      hospitals in Australia: a randomized controlled trial.
AB  - This study investigated the impact of a behaviorally based intervention designed
      to increase the number of hospitals that routinely provide effective smoking
      cessation programs for pregnant women. In Queensland, Australia, 70 publicly
      funded hospitals were matched on numbers of births and maternal socioeconomic
      status and randomly allocated to an awareness-only intervention group or a
      behaviorally based intervention group. Success was defined as the routine offer
      of an evidence-based smoking cessation program to at least 80% of the pregnant
      clients who smoke. At 1 month, 65% of the behaviorally based intervention
      hospitals agreed to provide materials about smoking cessation programs for their
      antenatal patients, compared with 3% of the awareness-only hospitals. After 1
      year, 43% of the intervention hospitals still provided the material, compared
      with 9% of the awareness-only hospitals. These findings show that a brief
      intervention to hospitals can encourage antenatal staff to provide smoking
      cessation materials to pregnant women.

PMID- 12238705
TI  - Supporting community-based prevention and health promotion initiatives:
      developing effective technical assistance systems.
AB  - As research evidence for the effectiveness of community-based prevention has
      mounted, so has recognition of the gap between research and community practice.
      As a result, state and local governments are taking a more active role in
      building the capacity of community-based organizations to deliver evidence-based
      prevention interventions. Innovations are taking place in the establishment of
      technical assistance or support systems to influence the prevention and health
      education activities of community-based organizations. Several challenges for
      technical assistance systems are described: (1) setting prevention priorities and
      allocating limited technical assistance resources, (2) balancing capacity
      building versus program dissemination efforts, (3) collaborating across
      categorical problem areas, (4) designing technical assistance initiatives with
      enough "dose strength" to have an effect, (5) balancing fidelity versus
      adaptation in program implementation, (6) building organizational cultures that
      support innovation, and (7) building local evaluative capacity versus
      generalizable evaluation findings.

PMID- 12238706
TI  - Care to care.

PMID- 12238707
TI  - Interviewing as therapy: researching parents' experiences of their child's life
      threatening illness requiring ECMO.
AB  - This retrospective study explores the views of eight parents' experience of their
      child's critical illness requiring extracorporeal membrane oxygenation (ECMO) as
      to whether the same research investigation might be carried out contemporaneously
      It is acknowledged that a viewpoint elicited retrospectively may be altered by
      time and, therefore, in advance of any such prospective study being carried out,
      ethical concerns regarding the gathering of data at such a traumatic time must be
      given consideration In addition to material collected for the primary study,
      further data were gathered in order to elicit how the research process itself was
      defined and experienced by the parent participants Views were elicited through an
      informal debriefing interview immediately following the primary research
      interview and a follow-up, evaluative, postal questionnaire distributed one week
      later.

PMID- 12238708
TI  - Use of the 'BRASS' to identify ICU patients who may have complex hospital
      discharge planning needs.
AB  - Intensive care unit (ICU) transition programmes and discharge liaison nurse roles
      have emerged because the move from the ICU to the general wards has been found to
      be problematic for patients, their families and even health care professionals As
      these programmes are costly, it is essential that they are delivered to those for
      whom positive outcomes are most likely to be achieved. This paper reports on the
      use of the Blaylock Risk Assessment Screening Score (BRASS) to identify ICU
      patients who are at risk of complex hospital discharge needs Use of BRASS at
      admission was not particularly specific: that is, it was not able to identify
      consistently those at risk of prolonged ICU and hospital stay and ICU
      readmission. BRASS was fairly sensitive, correctly identifying over 95% of
      individuals who did not have a prolonged hospital stay BRASS is easy to use, but
      may be no better than severity of illness scoring systems in identifying ICU
      patients who potentially have complex hospital discharge planning needs; if used,
      it should not be completed on ICU admission alone.

PMID- 12238709
TI  - The withdrawal of life support in adult intensive care: an evaluative review of
      the literature.
AB  - To ensure that intensive care is both cost-effective and humanitarian depends on
      a willingness to withdraw treatment once the prognosis is recognised as being
      hopeless, as the process of dying may be prolonged if futile treatment is
      continued Continuing advances in technology, science and professional care,
      raising new ethical, economic and legislative dilemmas, mean the decision to
      withdraw treatment in intensive care has become an issue of renewed concern These
      advances require both the development of scientific methods to support the
      decision-making process and an understanding of the ethical balance that
      underpins such decisions with particular reference to the intensive care nurse
      Whilst there is recognition that the families of patients who die in intensive
      care require ongoing support and bereavement care, there is little to suggest
      that the needs of the multidisciplinary personnel caring for these patients are
      understood or provided for This paper aims to explore quality end-of-life care,
      common medical practices, research into the role of the expert nurse in caring
      for the dying patient and new strategies for the incorporation of palliative care
      Strategies are proposed to translate the shared ownership, responsibility and
      accountability of clinical governance regarding these decisions into positive
      action, consensus and collaboration at both local and national level.

PMID- 12238710
TI  - Provision of orientation programmes for nurses in pediatric intensive care.
AB  - It has been recommended that nursing staff who are new to paediatric intensive
      care should be offered an orientation programme There is no guidance currently
      available to influence the content or duration of such a programme on a national
      level A multi-centre research study was carried out to identify the existing
      provision of orientation programmes and how beneficial these are perceived to be
      Supernumerary status and effective mentoring are seen as essential to the success
      of these programmes Many new starters perceive that they receive inadequate
      preparation on stress management and psychosocial issues National communication
      between paediatric intensive care educators will help to improve and develop
      orientation programme provision.

PMID- 12238711
TI  - Protocol for the administration of haemofiltration fluids and using patient group
      electrolytes direction.
AB  - A patient group direction (PGD) is a specific written instruction for the supply
      or administration of named medicines in an identified clinical situation The
      introduction of a PGD must demonstrate a benefit for patients Haemofiltration is
      widely accepted as the treatment of choice when caring for critically ill
      patients in acute renal failure on an intensive care unit The haemofiltration PGD
      improves patient care by providing standardisation in administration of fluids
      and electrolytes and enabling nurses to respond rapidly to changes in
      biochemistry during haemofiltration This paper describes the development and
      implementation of a protocol to enable nurses to administer haemofiltration
      fluids and electrolytes under a patient group direction.

PMID- 12238712
TI  - Communicating with the ventilated patient--a literature review.
AB  - This review will directly examine the role of the intensive care nurse as a
      communicator in the provision of holistic nursing care to the ventilated patient
      Frequent occurrences of breakdown in the process of communication are identified
      In many cases nurse communication with the patient is only on a task-orientated
      basis A lack of effective communication may be attributable to psychological
      problems related to 'ITU syndrome' The critical care nurse is at the forefront in
      the delivery of a first class National Health Service and a breakdown in
      communication between the nurse and their patient can be perceived as poor
      nursing care.

PMID- 12238713
TI  - Finding the leader within.

PMID- 12238714
TI  - Advanced life support in adults.

PMID- 12238715
TI  - Infant feeding choices for mothers who are HIV positive.
AB  - Current Department of Health advice for mothers who are HIV positive is not to
      breastfeed. The aim of this paper is to encourage debate on this subject among
      health-care professionals who care for such mothers. Both formula feeding and
      breastfeeding could be considered a risk in such circumstances, but information
      and options can be make this choice safer.

PMID- 12238717
TI  - An interdisciplinary approach to the management of dysphagia.
AB  - Patients with dysphagia are often inappropriately managed. However, nurses can be
      trained to screen for swallowing difficulties and the introduction of an
      interdisciplinary dysphagia management model can improve both the initial
      management of dysphagic patients and the appropriateness of referrals to speech
      and language therapists.

PMID- 12238718
TI  - Producing catheterisation guidelines for patients who have oliguria.
AB  - Little guidance is provided in the literature on whether and when to catheterise
      patients whose urine output is low. In response to this problem, one nurse in
      critical care developed an algorithm with a multidisciplinary group of colleagues
      that would provide a simple, step-by-step guide to reaching a decision on
      catheterisation in this group of patients.

PMID- 12238720
TI  - A nurse-led approach to secondary prevention of CHD in primary care.
AB  - In the July issue of Professional Nurse we summarised key recommendations set out
      in the National Service Framework for Coronary Heart Disease for primary care
      nurses. This paper describes one such strategy in practice, the nurse-led clinic,
      and demonstrates its effectiveness in tackling CHD patients' problems, including
      poor diet, smoking and an inactive lifestyle.

PMID- 12238719
TI  - Avoidance and management of peri-wound maceration of the skin.
AB  - Excessive wound exudate or other bodily fluids, such as urine or sweat, can cause
      skin maceration to occur around a wound, which may delay healing and lead to
      other complications. This paper examines means of preventing maceration while
      ensuring a moist wound-healing environment and looks at management techniques if
      the condition develops.

PMID- 12238724
TI  - Caring for older people through the National Service Framework.
AB  - The National Service Framework for older people could be described as the most
      important of the Government's frameworks because it covers the greatest number of
      people. This paper summarises key aspects of the NSF's eight standards for caring
      for older people and discusses the implications for nursing practice in
      hospitals, residential care homes and the community.

PMID- 12238725
TI  - Intravenous fluids: the options.

PMID- 12238726
TI  - Skin disease: a very visible problem.

PMID- 12238727
TI  - Do cannabinoid drugs have a therapeutic value as analgesics?
AB  - Laboratory research has shown promising results for using plant-derived,
      synthetic or endogenous cannabinoids for analgesia. However, human studies are
      few and far between and have been held up by the law and the lack of standardised
      extracts. This paper considers these drugs' potential uses in pain management.

PMID- 12238728
TI  - How to calculate drug dosage accurately: advice for nurses.
AB  - Nowhere is basic maths more important for nurses than when calculating drug
      doses. Simply having a GCSE in the subject does not seem to be good enough for
      the kind of mathematical calculations nurses need to be able to perform. However,
      following a few golden rules can simplify what at first appears to be a very
      complicated process.

PMID- 12238729
TI  - Improving knowledge of CHD.

PMID- 12238730
TI  - Osteoporosis knowledge, calcium intake, and weight-bearing physical activity in
      three age groups of women.
AB  - The purpose of this study was to determine the extent and integration of
      osteoporosis knowledge in three age groups of women and compare knowledge to
      calcium intake and weight-bearing physical activity (WBPA). In this cross
      sectional study, knowledge, calcium intake and WBPA were assessed using probe
      interviews, a food frequency and an activity questionnaire, respectively. Seventy
      five white women were separated into three groups: young (25-35 years), middle
      aged (36-46 years) and postmenopausal (50+ years). Concept maps were used to
      assess knowledge (concepts, integration and misconceptions). Calcium intakes from
      diet, supplements and fortified orange juice were estimated as were minutes of
      daily WBPA. Analysis of covariance was used to compare knowledge, calcium intake
      and WBPA by age group. Covariates included education, family history, physical
      problems making exercise difficult, and lactose intolerance. Chi square analysis
      was used to determine differences in these covariates across age groups.
      Correlations and regression analysis were used to determine relationships between
      knowledge and behaviors. Knowledge scores averaged 32-44 points (183 possible).
      Average calcium intake in all groups exceeded the Dietary Reference Intake's
      recommended Adequate Intake but 20-24% consumed less than 60% of the AI.
      Housework, walking at work, and standing at home and work accounted for 90% of
      WBPA. Knowledge about osteoporosis was limited and not associated with age, WBPA
      or calcium intake. Calcium intake and WBPA were not associated with age.
      Practitioners need to provide explicit information on osteoporosis and risk
      reducing behaviors to women of all ages.

PMID- 12238731
TI  - A survey of pharmacists' opinions and practices related to the sale of cigarettes
      in pharmacies-revisited.
AB  - The objective of the study was to follow-up on important findings from a 1996
      statewide survey of Indiana pharmacists regarding their opinions and practices
      related to the sale of cigarettes in pharmacies. More specifically, this study
      was designed to (1) collect 2001 state-wide data concerning the percentage of
      Indiana pharmacies selling cigarettes and to learn what pharmacists think about
      the sale of cigarettes in their stores; (2) compare these findings with results
      from a 1996 study; and collect new information on (3) whether a cigarette selling
      policy in pharmacies in which pharmacists are employed differs from their
      professional and personal values; (4) pharmacists' opinions related to state-wide
      initiatives on tobacco control in Indiana; and (5) the level of involvement with
      smoking cessation activities by community pharmacists. A 1996 survey instrument
      of Indiana pharmacists opinions and practices related to the sale of cigarettes
      in pharmacies served as the basis for questionnaire design. In addition, 11 new
      items were added to assess the three new objectives of the study. This
      questionnaire was administered to half of the 1,280 pharmacies in Indiana.
      Collected data were analyzed by using descriptive and inferential statistical
      methods. Findings reveal that independent pharmacies had significantly reduced
      their sale of cigarettes from 1996 while there was no significant change among
      retail chain pharmacies. Additionally, significantly more pharmacists in 2001
      believed that pharmacies should not sell cigarettes compared to five years ago.
      Also, more than three-fourths of pharmacists who worked in pharmacies that sold
      cigarettes felt it differed from their professional values. When it came to
      pharmacists involvement in tobacco control activities, results were mixed. This
      study found that the majority of pharmacists do not ask their patients about
      their smoking habits. In addition, an overwhelming majority of Indiana
      pharmacists were unfamiliar with a number of state public health
      programs/resources on smoking preven- tion and cessation. Nevertheless, it was
      very encouraging that nearly three-fourths of the pharmacies offer counseling
      programs for smokers who want to quit and more than one-half believed that
      increasing the state excise tax on cigarettes would be effective on tobacco
      control in Indiana.

PMID- 12238732
TI  - Developing profiles of postmenopausal women being prescribed estrogen therapy to
      prevent osteoporosis.
AB  - Postmenopausal women with estrogen deficiency are at high risk for osteoporosis.
      Estrogen therapy has been shown to be effective in preventing postmenopausal bone
      loss and maintaining bone mineral density. The increasing number of women at risk
      for osteoporosis and the high cost of treating this condition emphasizes the
      importance of preventing osteoporosis. This study was designed to identify trends
      and predictors of estrogen use for osteoporosis prevention among postmenopausal
      women. A retrospective, cross-sectional study was conducted using Behavioral Risk
      Factor Surveillance System data (1997-1999). Women 35 years and older who had
      passed menopause or were currently going through menopause were identified from
      the states including the BRFSS module that asked questions about estrogen use.
      Results showed an increasing prevalence in estrogen use from 1997 to 1999 for
      osteoporosis prevention. In 1999, almost a third of the postmenopausal women
      surveyed used estrogen to prevent osteoporosis. Prevalence was higher among women
      45-64 years of age, whites, and those with higher education levels. Physician
      counseling on the benefits and risks of estrogen therapy was the strongest
      predictor of estrogen use for prevention of osteoporosis. Insurance coverage and
      compliance with other preventive behaviors such as mammograms and Pap smears were
      also strongly associated with greater estrogen use. However, women who were at
      risk for acute drinking, not married, overweight or obese, and diabetic were all
      less likely to receive estrogen therapy for osteoporosis prevention. The
      relationships demonstrated between estrogen use and demographic characteristics,
      lifestyle behaviors and health care access and utilization factors underline the
      importance of targeting specific groups of women for promoting its protective
      effect against osteoporosis.

PMID- 12238733
TI  - A source of error in self-reports of pap test utilization.
AB  - The prevention and early detection of cervical cancer is achieved through women's
      regular use of Pap tests. Ascertaining adherence to Pap screening guidelines is
      often based on self-report, which may be unreliable. This study examined the
      reliability of Pap test self-reports and one potential source of error in them.
      We predicted that women having any gynecological examination (other than Pap
      tests) would falsely report having had a Pap test more often than women who had
      not experienced gynecological procedures. We compared self-reported Pap test
      utilization with medical records among 161 low-income women. Women with no Pap
      test in their medical record but who had experienced other gynecological
      procedures falsely reported a Pap test significantly more often than those women
      who actually received a Pap test or who had not received any gynecological
      procedure. Confusion over what type of gynecological procedures these women
      received could result in their under-utilization of Pap tests. Further, these
      findings question the validity of study findings based only on self-reported
      outcomes.

PMID- 12238734
TI  - The role of Abraham Lincoln in securing a charter for a homeopathic medical
      college.
AB  - In 1854, Abraham Lincoln was retained to prepare a state legislative proposal to
      charter a homeopathic medical college in Chicago. This was a complex task in view
      of the deep-seated animosity between allopathic or orthodox medical practitioners
      and irregular healers. Homeopathy was regarded as a cult by the nascent American
      Medical Association. In addition, the poor reputation of medical education in the
      United States in general, further complicated the project. Lincoln and
      influential individuals in Illinois lobbied legislators and succeeded in securing
      the charter. Subsequently, the Hahnemann Homeopathic Medical College accepted its
      first class in 1860 and with its successors remained in existence for almost
      sixty-five years.

PMID- 12238735
TI  - Attention deficit disorder in adults.
AB  - ADHD/ADD, once thought to occur only in children, is now recognized as continuing
      into adulthood in many people. In order to be labeled as such, signs and symptoms
      must start before age 7 and are primarily characterized by inattention,
      distractibility, and impulsiveness. Although the exact mechanism is unknown, a
      number of associated neurochemical and structural abnormalities have been
      observed. This disorder can negatively affect the educational, social, and
      occupational lives of those who suffer from its symptoms. It interferes with the
      ability to establish and maintain close relationships. Pharmacotherapy remains
      the primary mode of treatment. Stimulants such as dextroamphetamine and
      methylphenidate are the main drugs utilized; they are available in immediate and
      longer duration versions. Bupropion is another important medicinal option, and
      there are a variety of other miscellaneous medications to consider, including
      modafinil, venlafaxine, tricyclic antidepressants, and guanfacine. Psychotherapy
      is shown to help control impulsiveness, form more satisfactory relationships,
      rear children more effectively, and improve organizational and problem-solving
      skills.

PMID- 12238736
TI  - Neuromotor dysfunction in early psychosis.
AB  - Neuromotor dysfunction, particularly extrapyramidal signs and symptoms (EPSS),
      plays an important role in the assessment and treatment of patients in the early
      stages of psychotic disorders such as schizophrenia. By blocking dopamine D2
      receptors, antipsychotic medications can produce EPSS, including tardive
      dyskinesia. EPSS is also observed in a third or more of patients first presenting
      with a psychotic disorder, prior to initiation of antipsychotic pharmacotherapy.
      This suggests that abnormalities in neuromotor control may be an integral
      component of the brain mechanisms associated with psychosis. Atypical
      antipsychotic agents can alleviate psychosis without inducing EPSS. Preexisting
      EPSS may be corrected.

PMID- 12238737
TI  - Extrapyramidal side effects of antipsychotic treatment: scope of problem and
      impact on outcome.
AB  - Previously, clinicians worked with antipsychotic drugs (conventional or typical)
      that almost invariably caused extrapyramidal symptoms (EPS) at clinically
      effective doses. This led to the false impression that all antipsychotics were
      the same, and that EPS were an unavoidable consequence of effective antipsychotic
      therapy. EPS adversely impact several aspects of antipsychotic efficacy and
      tolerability, thereby worsening outcome of afflicted individuals. EPS reduce
      beneficial effects of antipsychotic treatment on the negative, cognitive, and
      mood symptom domains, while increasing the risk of tardive dyskinesia and
      reducing compliance. By definition, the newer generation of "atypical"
      antipsychotic agents are significantly better than conventional agents with
      regard to EPS (i.e., they are clinically effective at doses at which they do not
      cause EPS). Pharmacologically, this difference is expressed in the greater degree
      of separation between respective dose response curves for antipsychotic and EPS
      effects observed for "atypical" in contrast to conventional agents. Clinically,
      this EPS advantage of atypical antipsychotics translates into several important
      benefits, including better negative symptom efficacy, less dysphoria, less
      impaired cognition, a lower risk of TD, and better overall outcome.

PMID- 12238739
TI  - The effect of loss and trauma on substance use behavior in individuals seeking
      support services after the 1995 Oklahoma City bombing.
AB  - In this study, we examined the effect of trauma exposure on substance use
      behaviors, specifically tobacco and alcohol use, in a group of 84 individuals who
      sought supportive services after the 1995 Oklahoma City bombing. A self-report
      instrument was used to assess demographics, sensory exposure, injury,
      interpersonal exposure through relationship with victims, peritraumatic reaction,
      grief, posttraumatic stress, worry about safety, functional impairment, and
      changes in smoking and drinking. Those who reported increased smoking had higher
      scores on peritraumatic reaction, grief, posttraumatic stress, worry about
      safety, and trouble functioning. Those who reported increased alcohol intake had
      higher scores on injury, peritraumatic reaction, grief, posttraumatic stress,
      worry about safety, and trouble functioning. Sensory exposure and interpersonal
      exposure were not significantly different between those with and without
      increased smoking or drinking. Although no causal relationship can be assumed,
      our findings indicate an association of grief and posttraumatic stress with
      increased substance use behaviors in disaster victims.

PMID- 12238738
TI  - The relationship between DST results and suicidal behavior.
AB  - The authors assessed the relationship between dexamethasone suppression test
      (DST) results and suicidal ideations and behavior. Four-hundred-twenty-three mood
      disorder patients admitted to a tertiary care medical center were administered
      the DST from 1978 to 1981. The patients were subsequently followed up to
      determine death status using a record-linkage method. More than 44% had abnormal
      cortisol suppression (nonsuppressors) at the index admission. Suppressors and
      nonsuppressors did not differ significantly with respect to frequency of suicidal
      ideations or completed suicides. Suppressors were significantly more likely than
      nonsuppressors to have a history of suicide attempts or to have a suicide attempt
      following hospital discharge. Using logistic regression, and controlling for
      several important variables including diagnosis, maximum postdexamethasone
      cortisol was not significantly associated with suicide, suicidal ideation, or
      suicide attempts. We conclude that an abnormal DST is not useful as a predictor
      of suicidal behavior.

PMID- 12238740
TI  - Agitated depression: unipolar? Bipolar? Or both?
AB  - The classification of agitated depression (major depressive episode (MDE) plus
      psychomotor agitation) in mood disorders is unclear. DSM-IV is neutral on this
      point. As antidepressants may increase agitation, a better understanding of
      agitated depression is important for clinical practice. Study aim was to find if
      agitated depression was closer to bipolar or to unipolar disorders, by studying
      its association with variables typically related to bipolar disorders (early
      onset, many recurrences, more atypical features, more bipolar family history),
      and by studying its association with bipolar II disorder. Consecutive 151
      unipolar and 226 bipolar II psychoactive drug-free MDE outpatients were
      interviewed with the Structured Clinical Interview for DSM-IV, when presenting
      for MDE treatment. Agitated MDE patients were compared with nonagitated MDE
      patients. Statistics were t test for means, two-sample test of proportion, and
      logistic regression (STATA 7). Agitated MDE was present in 85 patients (22.5%).
      It had significantly more bipolar II disorder patients (80.0% vs. 54.1%, p =
      0.0000), more females, lower age at onset, longer duration of illness, more MDE
      recurrences, more atypical features, more MDE symptoms, and more family history
      of bipolar disorders, than nonagitated MDE. To control for the possible
      confounding effect of bipolar II disorder, logistic regression was used. All the
      significant differences became nonsignificant. Results might suggest that
      agitated MDE might be closer to the bipolar spectrum than to unipolar disorder,
      because it was associated with variables typically distinguishing bipolar from
      unipolar disorders, and with bipolar II disorder. Further studies on this topic
      are needed.

PMID- 12238741
TI  - Individual actions or social issues? Towards ethical biotech futures in a civil
      society.

PMID- 12238742
TI  - An interview with Judith A Oulton.

PMID- 12238743
TI  - The modification of emotional responses: a problem for trust in nurse-patient
      relationships?
AB  - This article examines one aspect of the criticism of inauthenticity that can be
      levelled against the trustworthiness of professional relationships in general and
      nurse-patient relationships in particular. The overall question is: are such
      relationships inherently trustworthy or untrustworthy, from the patient's point
      of view? The author concludes that, in spite of legitimate grounds for concern,
      and while it remains true that nurse-patient relationships may be untrustworthy,
      they are not inherently so for reasons of inauthenticity relating to emotional
      labour. The arguments used to defend this claim take their force from the idea
      that different criteria may be needed to assess the authenticity of nurse-patient
      relationships from those used to evaluate authenticity in ordinary social
      relationships. The utility of Hochschild's idea of 'deep' acting, as offering a
      useful model for the management of emotions in nursing, is examined and rejected.

PMID- 12238744
TI  - An exploration of the relationship between patient autonomy and patient advocacy:
      implications for nursing practice.
AB  - The purpose of this article is to examine whether patient/client autonomy is
      always compatible with the nurse's role of advocacy. The author looks separately
      at the concepts of autonomy and advocacy, and considers them in relation to the
      reality of clinical practice from professional, ethical and legal perspectives.
      Considerable ambiguity is found regarding the legitimacy of claims of a unique
      function for nurses to act as patient advocates. To act as an advocate may put
      nurses at personal and professional risk. It may also be deemed arrogant and
      insulting to other health care professionals. Patient autonomy can be seen as a
      subcategory of the right of every individual to self-determination, and as such
      is protected by law. However, it is questionable whether the traditionally
      paternalistic approach to health care provision truly respects the autonomous
      rights of each patient. The author considers examples and cases from the
      literature that resulted in professional and/or personal difficulties for the
      nurses involved, and also reflects on an incident from her own practice where a
      positive outcome was achieved that demonstrated compatibility between the
      concepts under consideration.

PMID- 12238745
TI  - Decision making in health care: limitations of the substituted judgement
      principle.
AB  - The substituted judgement principle is often recommended as a means of promoting
      the self-determination of an incompetent individual when proxy decision makers
      are faced with having to make decisions about health care. This article
      represents a critical ethical analysis of this decision-making principle and
      describes practical impediments that serve to undermine its fundamental purpose.
      These impediments predominantly stem from the informality associated with the
      application of the substituted judgement principle. It is recommended that the
      principles upon which decisions are made about health care for another person
      should be transparent to all those involved in the process. Furthermore, the
      substituted judgement principle requires greater rigour in its practical
      application than currently tends to be the case. It may be that this principle
      should be subsumed as a component of advance directives in order that it fulfils
      its aim of serving to respect the self-determination of incompetent individuals.

PMID- 12238746
TI  - A fundamental ethical approach to nursing: some proposals for ethics education.
AB  - The purpose of this article is to explore a fundamental ethical approach to
      nursing and to suggest some proposals, based on this approach, for nursing ethics
      education. The major point is that the kind of nursing ethics education that is
      given reflects the theory that is held of nursing. Three components of a
      fundamental ethical view on nursing are analysed more deeply: (1) nursing
      considered as moral practice; (2) the intersubjective character of nursing; and
      (3) moral perception. It is argued that the fundamental ethical view on nursing
      goes together with a virtue ethics approach. Suggestions are made for the ethics
      education of nurses. In particular, three implications are considered: (1) an
      attitude versus action-orientated ethics education; (2) an integral versus
      rationalistic ethics education; and (3) a contextual model of ethics education.
      It will also be shown that the European philosophical background offers some
      original ideas for this endeavour.

PMID- 12238747
TI  - Examining ethics in practice: health service professionals' evaluations of in
      hospital ethics seminars.
AB  - This article reviews practitioners' evaluations of in-hospital ethics seminars. A
      qualitative study included 11 innovative in-hospital ethics seminars, preceded
      and followed by interviews with most participants. The settings were obstetric,
      neonatal and haematology units in a teaching hospital and a district general
      hospital in England. Fifty-six health service staff in obstetric, neonatal,
      haematology, and related community and management services participated; 12
      attended two seminars, giving a total of 68 attendances and 59 follow-up
      evaluation interviews. The 11 seminars facilitated by an ethicist addressed the
      key local concerns of staff about the social and ethical consequences of advances
      in genetics and their impact on professional policies and practice. Seminar
      agendas were drawn from prior interviews with 70 staff members. During evaluation
      interviews, participants commented on general aspects that they had enjoyed, how
      the sessions could be improved, timing, the mix of participants, the quality of
      the facilitation, whether sessions should be more challenging, after-effects of
      sessions, and interest in attending seminars and contacting the ethicist in
      future. Participants valued the increased interprofessional understanding and
      coherent discussion of many pressing issues that addressed important though
      seldom discussed ethical questions. The seminars worked well in the different
      hospitals and specialties.

PMID- 12238748
TI  - Moving from codes of ethics to ethical relationships for midwifery practice.
AB  - This discussion examines the emergence of professional codes of ethics,
      influences that shape contemporary midwifery ethics, and the adequacy of codes to
      actualize values embedded in the midwifery ethics discourse. It considers the
      traditions of professional practice, the impact of institutionalization on health
      care, the application of a code of practice as a recent addition to those
      traditions, and the strengths and weaknesses of codes of ethics as models for
      ethical responses. That is, it sets out to articulate and deconstruct existing
      frames of ethical response. The ethics of strangers (normative theory and
      abstract principles) are rejected as inadequate, and the ethics of intimates
      (feminist-relational ethics) are proposed as a more adequate guide for well-woman
      centred midwifery practice.

PMID- 12238750
TI  - Open disclosure: an Australian project.

PMID- 12238749
TI  - Older persons' ethical problems involving their health.
AB  - Although older persons (aged 65 years and older) experience stressful ethical
      problems involving their health, research is lacking about this phenomenon. The
      purpose of this study was to describe and examine the content and basic nature of
      older persons' ethical problems concerning their health. The conceptual framework
      and method combined ethical enquiry and phenomenology. The participants were 18
      older persons and 12 of their children or grandchildren (for contextual
      understanding). The 19 women and 11 men, 73% of whom were Caucasian, described
      184 ethical problems, from which emerged 10 content categories. The basic nature
      of the ethical problems consisted of conflict, resolution and rationale. The
      results could assist health professionals to promote older persons' ethical
      decision making, quality of life, and good death.

PMID- 12238751
TI  - The importance of end-of-life-treatment preferences among older adults.

PMID- 12238752
TI  - Laser capture microdissection in 2-D co-culture models as a tool to study tumor
      stroma interactions.

PMID- 12238753
TI  - Internally controlled poly(A) tail assay to study gene regulation.

PMID- 12238754
TI  - Simple device to deliver beads to 96-well plates for rapid resuspension of
      bacterial pellets.

PMID- 12238755
TI  - Improved reliability of allele-specific PCR.

PMID- 12238756
TI  - Construction of a broad host range cloning vector conferring triclosan
      resistance.

PMID- 12238757
TI  - Analysis of the detection limit on a microelectronic array.

PMID- 12238758
TI  - Internal controls for normalizing DNA arrays.

PMID- 12238759
TI  - Multicolor post-PCR labeling of DNA fragments with fluorescent ddNTPs.

PMID- 12238760
TI  - Temperature non-homogeneity in rapid airflow-based cycler significantly affects
      real-time PCR.

PMID- 12238761
TI  - Analysis of result variability from high-density oligonucleotide arrays comparing
      same-species and cross-species hybridizations.
AB  - There exists a significant limitation in the variety of organismsfor which
      microarrays have been developed because of a lack of genomic sequence data. A
      near-term solution to this limitation is to use microarrays designed for one
      species to analyze RNA samples from closely related species. The assumption is
      that conservation of gene sequences between species will be sufficient to
      generate a reasonable amount of good-quality data. While there have been
      relatively few published reports describing the use of microarrays for cross
      species hybridizations, this technique is potentially a powerful tool for
      understanding genomics in model organisms such as nonhuman primates. Here we
      describe the analysis and comparison of hybridization characteristics and data
      variability from a set of cross-species (rhesus macaque) and same-species (human)
      hybridization experiments using human high-density Affymetrix oligonucleotide
      arrays. The data reveal that a large fraction of probe sets are effective at
      transcript detection in the cross-species hybridization, validating the
      application of cross-species hybridizations for nonhuman primate genomics
      research.

PMID- 12238762
TI  - Determination of methylation site of DNA-methyltransferase NlaX by a hybrid
      method.
AB  - Using a new method based on a combination of bisulfite reaction, the repair
      enzyme uracil-DNA glycosylase, and synthetic oligodeoxyribonucleotides, the
      methylation site of DNA-methyltransferase NlaX (M.NlaX) from Neisseria lactamica
      was established to be the inner cytosine in the double-stranded pentanucleotide
      recognition sequence 5'-CCNGG-3' (where N = any nucleoside). 5-Methylcytosine
      (m5C) type modification by M-N1aX was confirmed by the use of oligonucleotide
      substrates that contain 5-fluoro-2'-deoxycytidine.

PMID- 12238763
TI  - Resuspension of DNA sequencing reaction products in agarose increases sequence
      quality on an automated sequencer.
AB  - We are investigating approaches to increase DNA sequencing quality. Since a
      majorfactor in sequence generation is the cost of reagents and sample
      preparations, we have developed and optimized methods to sequence directly
      plasmid DNA isolated from alkaline lysis preparations. These methods remove the
      costly PCR and post-sequencing purification steps but can result in low sequence
      quality when using standard resuspension protocols on some sequencing platforms.
      This work outlines a simple, robust, and inexpensive resuspension protocol for
      DNA sequencing to correct this shortcoming. Resuspending the sequenced products
      in agarose before electrophoresis results in a substantial and reproducible
      increase in sequence quality and read length over resuspension in deionized water
      and has allowed us to use the aforementioned sample preparation methods to cut
      considerably the overall sequencing costs without sacrificing sequence quality.
      We demonstrate that resuspension of unpurified sequence products generated from
      template DNA isolated by a modified alkaline lysis technique in low
      concentrations of agarose yields a 384% improvement in sequence quality compared
      to resuspension in deionized water. Utilizing this protocol, we have produced
      more than 74,000 high-quality, long-read-length sequences from plasmid DNA
      template on the MegaBACET 1000 platform.

PMID- 12238764
TI  - fRFLP and fAFLP: medium-throughput genotyping by fluorescently post-labeling
      restriction digestion.
AB  - Genome-scale studies of population structure and high-resolution mapping of
      genetically complex traits both require techniques for accurately and efficiently
      genotyping large numbers of polymorphic sites in multiple individuals. Many high
      throughput genotyping technologies require the purchase of expensive equipment or
      consumables and are therefore out of reach of some individual research
      laboratories. Conversely, less expensive technologies are often labor intensive
      so that the effort involved in typing large numbers of samples or polymorphic
      sites is prohibitive. Here we present a method of fluorescently post-labeling
      restriction digestion using standard dye-terminator sequencing chemistry so that
      RFLP and AFLP products can be visualized on an automated sequencer This labeling
      method is efficient, inexpensive, easily multiplexed, and requires no unusual
      equipment or reagents, thus striking a balance between cost and throughput that
      should be appropriate for many research groups and core facilities.

PMID- 12238765
TI  - GWFASTA: server for FASTA search in eukaryotic and microbial genomes.
AB  - Similarity searches are a powerful method for solving important biological
      problems such as database scanning, evolutionary studies, gene prediction, and
      protein structure prediction. FASTA is a widely used sequence comparison tool for
      rapid database scanning. Here we describe the GWFASTA server that was developed
      to assist the FASTA user in similarity searches against partially and/or
      completely sequenced genomes. GWFASTA consists of more than 60 microbial genomes,
      eight eukaryote genomes, and proteomes of annotatedgenomes. Infact, it provides
      the maximum number of databases for similarity searching from a single platform.
      GWFASTA allows the submission of more than one sequence as a single query for a
      FASTA search. It also provides integrated post-processing of FASTA output,
      including compositional analysis of proteins, multiple sequences alignment, and
      phylogenetic analysis. Furthermore, it summarizes the search results organism
      wise for prokaryotes and chromosome-wise for eukaryotes. Thus, the integration of
      different tools for sequence analyses makes GWFASTA a powerful toolfor
      biologists.

PMID- 12238766
TI  - Thirty-cycle temperature optimization of a closed-cycle capillary PCR machine.
AB  - The performance of a novel thermal cycler has been characterized in a 30-cycle
      PCR. The device consists of a microcapillary equipped with bidirectional pressure
      driven flow and in situ optical position sensors. A 1-microL droplet of reaction
      mixture moves between three heat zones in a 1-mm i.d., oil-filled capillary using
      a multi-element scattered light detector and active feedback. The design permits
      time and number of cycles to be changed without hardware modification, unlike
      other flow-in-capillary PCR systems. Temperature optimization has been performed
      on the three PCR heat steps. The optimal denaturation temperature is 94 degrees C
      96 degrees C, which is identical to commercial machines. The optimal extension
      temperature of 62 degrees C-66 degrees C is lower than reported for Taq DNA
      polymerase (70 degrees C-80 degrees C) because of the high enzyme concentration
      and/or the absence of detergent in the PCR mixture. The optimal annealing
      temperature seems to be the same as the optimal extension temperature. This is
      because extension occurs when the sample is inside of the annealing heat zone.
      Annealing takes place as the sample travels between heat zones. Device speed (23
      minfor 30 cycles without time optimization) is competitive with other rapid PCR
      designs for efficiencies comparable to a commercial machine.

PMID- 12238767
TI  - Linear amplification of catalyzed reporter deposition technology on nylon
      membrane microarray.
AB  - The application of microarray analysis to gene expression from limited tissue
      samples has not been very successful because of the poor signal qualityfrom the
      genes expressed at low levels. Here we discussed the use of catalyzed reporter
      deposition (CARD) technology to amplify signals from limited RNA samples on nylon
      membrane cDNA microarray. When the input RNA level was greater than 10 microg,
      the genes expressed at high levels did not amplify in proportion to those
      expressed at low levels. Compared to conventional colorimetric detection, the
      CARD method requires less than 10% of the total RNA used for amplification of
      signal displayed onto a nylon membrane cDNA microarray. Total RNA (5-10 microg),
      as one can extract from a limited amount of specimen, was determined to produce a
      linear correlation between the colorimetric detection and CARD methods. Beyond
      this range, it can cause a nonlinear amplification of highly expressed and low
      abundance genes. These results suggest that when amplification is needed for any
      applications using the CARD method, including DNA microarray experiments,
      precaution has to be taken in the amount of RNA used to avoid skew amplification
      and thus misleading conclusions.

PMID- 12238768
TI  - Affinity tag for protein purification and detection based on the disulfide-linked
      complex of InaD and NorpA.
AB  - Affinity tags are not only used for the expression and purification of
      recombinant proteins but also for the detection of protein-protein interactions.
      Common problems with many affinity tags are excessive length, which may interfere
      with the structure and function of tagged proteins, and low affinity and/or
      specificity for primary detection and purification agents. Preliminary results
      suggest that the C-terminalfive residues of the Drosophila protein NorpA, based
      on the short, covalent interaction they make with the N-terminal PDZ domain
      (PDZI) of InaD, are useful as a general affinity tag. First, a PDZI-alkaline
      phosphatase fusion protein specifically detects both its physiological ligand and
      a heterologous protein expressing the NorpA C-terminal five residues. The
      interaction of PDZI with a NorpA-tagged protein is reversible by a reducing
      agent, which allows nitrocellulose membranes to be stripped completely and
      reused. In addition, a NorpA-tagged protein can specifically bind to immobilized
      PDZI resin, while other cellular proteins are washed through. After washing, the
      NorpA-tagged protein is eluted by a reducing buffer. The NorpA tag's short length
      makes it the smallest affinity tag available, and its specific and high-affinity
      interaction with PDZI could yield a powerful system that improves on currently
      available technology.

PMID- 12238769
TI  - Improved version of the red fluorescent protein (drFP583/DsRed/RFP).
AB  - GFP has established itself as a highly useful tool throughout many areas of
      modern biology. Recently, the novel fluorescent protein drFP583, also termed
      DsRed or RFP, was clonedfrom a coral of the Discosoma genus. The protein is only
      weakly homologous to GFP and has a red emission spectrum, which makes drFP583 an
      attractive candidate for in vivo double labeling together with GFP variants.
      However, wildtype drFP583 has several drawbacks, including inefficient folding of
      the protein, extremely slow maturation of the chromophore, and tetramerization
      even in dilute solutions. Here we report on important improvements to this
      reporter that lead to higher levels of fluorescent drFP583 species in the cell.
      We further characterized our best mutant for applications in yeast and mammalian
      cell biology.

PMID- 12238770
TI  - Formalin removal from archival tissue by critical point drying.
AB  - The extraction of high-quality nucleic acid may be problematic in formalin-fixed
      tissues because of cross-linking between proteins and DNA. Old fixed tissue
      specimens do produce fragmented DNA (<1.2 kb), which is only used for PCR
      amplification. Here we show that high molecular weight DNA (>194 kb) can be
      successfully extracted from fixed tissue samples (16-70 years old) by gradual
      dehydration and critical point drying. The reliability of extracted DNA was
      measured by its ability to serve as a template for the amplification of mtDNA
      fragments (403 and 1198 bp) and an nDNA fragment (1844 bp). In addition,
      fingerprinting analysis was performed using DNA from fixed human tissue to ensure
      the ability of extracted DNA to hybridize with the DNA probe. DNA derived by this
      method can be subject to amplification, complete digestion by restriction
      endonuclease, and hybridization.

PMID- 12238771
TI  - Long oligonucleotide arrays on nylon for large-scale gene expression analysis.
AB  - To date, most studies of multigenic expression patterns by long DNA array have
      used DNA fragments as probes. These probes are usually obtained as PCR products,
      and this represents a time-consuming and error-prone approach, requiring strict
      quality control. The present study examines the use of 40- and 70-mer synthetic
      oligonucleotides as probes for DNA array analysis with radioactive labeled
      targets. Design, spotting onto nylon filters, and hybridization conditions were
      determined and optimized. In this approach, the sensitivity and the specificity
      of the hybridization appear comparable to the conventional long DNA probes assay,
      permitting the analysis of small samples of approximately 1 microg total RNA. The
      long oligonucleotide array thus provides a very convenient method for the
      analysis of gene expression patterns in biological specimens and in clinical
      research.

PMID- 12238772
TI  - Comparison of fluorescent tag DNA labeling methods used for expression analysis
      by DNA microarrays.
AB  - Gene expression profiling by DNA microarrays has found wide application in many
      fields of biomedical research. The protocols for this technique are not yet
      standardized, and for each given step in microarray analysis a number of
      different protocols are in use. As a consequence, results obtained in different
      laboratories can be difficult to compare. Of particular importance in this
      respect are the methods for the preparation of fluorescent cDNA probes that
      should quantitatively reflect the abundance of different mRNAs in the two samples
      to be compared. Here we systematically evaluate and compare five different
      published and/or commercial principles for the synthesis offluorescently labeled
      probes for microarray analysis (direct labeling, 77 RNA polymerase amplification,
      aminoallyl labeling, hapten-antibody enzymatic labeling, and 3-D multi-labeled
      structures). We show that individual labeling methods can significantly influence
      the expression pattern obtained in a microarray experiment and discuss the
      respective benefits and limitations of each method.

PMID- 12238773
TI  - DNA methylation: a profile of methods and applications.
AB  - Ever since methylcytosine was found in genomic DNA, this epigenetic alteration
      has become a center of scientific attraction, especially because of its relation
      to gene silencing in disease. There is currently a wide range of methods designed
      to yield quantitative and qualitative information on genomic DNA methylation. The
      earliest approaches were concentrated on the study of overall levels of
      methylcytosine, but more recent efforts havefocused on the study ofthe
      methylation status of specific DNA sequences. Particularly, optimization of the
      methods based on bisulfite modification of DNA permits the analysis of limited
      CpGs in restriction enzyme sites (e.g., combined bisulfite restriction analyses
      and methylation-sensitive single nucleotide primer extension) and the overall
      characterization based on differential methylation states (e.g., methylation
      specific PCR, MethyLight, and methylation-sensitive single-stranded
      conformational polymorphism) and allows very specific patterns of methylation to
      be revealed (bisulfite DNA sequencing). In addition, novel methods designed to
      search for new methylcytosine hot spots have yielded further data without
      requiring prior knowledge of the DNA sequence. We hope this review will be a
      valuable tool in selecting the best techniques to address particular questions
      concerning the cytosine methylation status of genomic DNA.

PMID- 12238774
TI  - Detection of mutations in exon 8 of TP53 by temperature gradient 96-capillary
      array electrophoresis.
AB  - Various capillary electrophoresis applications have increasingly been utilized in
      mutation detection. Separation of two species is either based on secondary
      structure or differences in melting of DNA due to the mutation. Detection of the
      mutant is based on its mobility difference in the sieving matrix. We have adapted
      a regular 96-capillary sequencing instrument, the MegaBACE 1000, for mutation
      detection based on thermodynamic stability and mobility shift during
      electrophoresis. Denaturation of the lower melting domain of the DNA was achieved
      with a gradually decreasing temperature gradient in combination with a chemical
      denaturant. Samples were analyzed for mutants in exon 8 of the TP53 genefrom
      tumor samples and controls. Genomic DNA was PCR-amplified with one fluorescein
      labeled primer and one GC-clamped primer, diluted in water, and analyzed by
      temperature gradient 96-capillary array electrophoresis. Tumor samples and PCR
      reconstruction experiment samples were resolved by capillary gel electrophoresis
      under appropriate temperature gradient denaturing conditions. Ninety-six samples
      were analyzed in one run, with an analysis time of 30 min and a sensitivity to
      detect mutated alleles in wild-type background down to 0.4%. The technique proved
      to be robust, in that the gradient compensatesfor temperature differences within
      the capillary chamber; thus, each capillary will pass through the optimal
      separating conditions around the theoretical melting temperature for TP53 exon 8,
      separating homoduplexes and heteroduplexes. This technique is applicable to any
      sequence previously analyzed by DNA melting gel techniques or sequences harboring
      iso-melting domains of 100-120 bp.

PMID- 12238775
TI  - Diabetes, obesity, and Acrp30/adiponectin.

PMID- 12238776
TI  - Microarray gene expression profiling of angiogenesis inhibitors using the rat
      aortic ring assay.
AB  - The rat aortic ring assay has been previously described as a useful ex vivo model
      for analyzing the biological activity of various inhibitors of angiogenesis. Rat
      aortic rings are exposed to antiangiogenic agents for a five-day incubation
      period. Then, the degree of microvessel outgrowth from the rings is analyzed and
      quantified. In contrast to most in vitro angiogenesis assays, the rat aortic ring
      model provides a unique microenvironment to evaluate the interaction of various
      cell types and biological factors for their influence on angiogenesis. Microarray
      analysis is an accepted method for the evaluation of gene expression profiles and
      can be used to better understand changes in gene expression that occur when rat
      aortic rings are exposed to a particular biological agent. Here we describe a
      method of using microarray technology to evaluate the modulation of gene
      expression in angiogenesis using the rat aortic ring assay.

PMID- 12238777
TI  - Development of multiple cloning site cis-vectors for recombinant adeno-associated
      virus production.
AB  - Recombinant adeno-associated virus (rAAV) has become a very popular gene therapy
      vector in the past several years. A cis-plasmid is used to generate the rAAV
      stocks. In this plasmid, the entire expression cassette is incorporated between
      two AAV inverted terminal repeats. The construction of cis-plasmid has been
      problematic because of the high-frequency recombination of the viral inverted
      terminal repeats. Here we describe the design and construction of several
      multiple cloning site cis-plasmids that are driven by five different promoters,
      including the ubiquitous cytomegalovirus enhancer/chicken beta-actin (CAG),
      cytomegalovirus (CMV), rous sarcoma virus (RSV), simian virus 40 (SV40), and a
      muscle-specific promoter (CK6). The application of these multiple cloning site
      cis-plasmids improves the cloning efficiency. As an example of the utilization of
      these multiple cloning site vectors, the prokaryotic beta-galactosidase cDNA was
      cloned in the multiple cloning site cis-plasmids. High-level rAAV-mediated beta
      galactosidase expression was achieved in HeLa cells from CAG, CMV, RSV and SV40
      promoters, respectively, but notfrom the CK6 promoter. In vivo application in the
      adult mdx mouse (mouse model for Duchenne muscular dystrophy) muscle revealed
      efficient transgene expression from CMV and CK6 promoters, followed by CAG and
      RSV promoters. The SV40 promoter was the least efficient.

PMID- 12238778
TI  - Production of antigen-specific human monoclonal antibodies: comparison of mice
      carrying IgH/kappa or IgH/kappa/lambda transloci.
AB  - Here we compare human monoclonal antibody (MAb) production from mouse strains
      that carry disruptions of their endogenous mouse IgH/IgK loci and harbor human
      IgM + Igkappa(BABkappa) or human IgM + Igkappa + IgA transloci (BABkappa,lambda).
      We found that whereas both strains proved effective for the isolation of antigen
      specific IgM antibodies, many of the IgM MAbs elicited from BABkappa comprise
      human mu chains that are associated with mouse lambda chains. In contrast,
      BABkappa,lambda mice gave rise to fully functional, polymeric human IgM
      antibodies comprising both human IgH and human IgL chains. Therefore, the
      inclusion of a human Iglambda translocus (in addition to the human IgH + Igkappa
      transloci) not only diminishes problems of endogenous mouse Iglambda expression
      but also provides a strain of mice that yields fully human MAbs to a wide range
      of antigens, as witnessed by the isolation of MAbs to human blood cells, tumor
      cell lines, and an immunoglobulin idiotype.

PMID- 12238779
TI  - Stable, sensitive, fluorescence-based method for detecting cAMP.
AB  - cAMP is a universal secondary messenger that connects changes in the
      extracellular environment, as detected by cell surface receptors, to
      transcriptional changes in the nucleus. Since cAMP-mediated signal transduction
      plays a role in critical cell functions and human diseases, monitoring its
      activity can aid in understanding these responses and the process of drug
      discovery. This report examines the performance of a fluorescence-based
      competitive immunoassay in 384-well microplate format. Using purified cAMP as a
      competitor the estimated detection limit was determined to be 0.1 nM and Z'
      factor was greater than 0.83, which indicates that the assay is of high quality
      and one of the most sensitive assays currently on the market. Of note, the
      results obtained were similar whether the reaction was allowed to proceed for 10
      min or up to 60 min. Next, HEK 293 cells were treated with the promiscuous
      adenylate cyclase activator, forskolin, and the beta-adrenoceptor agonist,
      isoproterenol. The resultant average EC50 values were 11 microM and 123 nM,
      respectively, which correspond to those found in the literature. Together, these
      results demonstrate that this assay is afast, accurate, non-radioactive method
      that is ideal for high-throughput screening.

PMID- 12238781
TI  - Cytocompatibility of new phthalate ester-free tissue conditioners in vitro.
AB  - The estrogenic activity of phthalate esters for dental use as plasticizers was
      concerned. To study the feasibility of candidate chemicals for phthalate tissue
      conditioners, three candidate plasticizers, di-n-butyl sebacate, acetyl tributyl
      citrate and tri-n-butyl phosphate together with conventional plasticizers were
      examined for estrogenic activity and cytotoxicity using three estrogenicity
      assays, human gingival fibroblasts and living skin equivalent. None of the three
      candidate plasticizers showed any estrogenic activity at the concentrations
      tested by the three assays. Di-n-butyl sebacate, acetyl tributyl citrate and
      their prototype tissue conditioners were weakly to negligibly cytotoxic, while
      tri-n-butyl phosphate and its prototype tissue conditioner yielded the strongest
      cytotoxicity among the six plasticizers tested. In particular, the cytotoxicities
      of di-n-butyl sebacate and its prototype tissue conditioners were significantly
      weaker than the others and the conventional plasticizers. The results suggested
      that di-n-butyl sebacate and acetyl tributyl citrate could be candidate chemicals
      for phthalate ester-free tissue conditioners.

PMID- 12238780
TI  - A simplified numerical simulation method of bending properties for glass fiber
      cloth reinforced denture base resin.
AB  - The purpose of this study was to propose a new numerical modeling of the glass
      fiber cloth reinforced denture base resin (GFRP). The proposed model is
      constructed with an isotropic shell, beam and orthotropic shell elements
      representing the outmost resin, interlaminar resin and glass fiber cloth,
      respectively. The proposed model was applied to the failure progress analysis
      under three-point bending conditions, the validity of the numerical model was
      checked through comparisons with experimental results. The failure progress
      behaviors involving the local failures, such as interlaminar delamination and
      resin failure, could be simulated using the numerical model for analyzing the
      failure progress of GFRP. It is concluded that the model was effective for the
      failure progress analysis of GFRP.

PMID- 12238783
TI  - Mechanical properties of light-cured composite resins cured through filters that
      simulate enamel.
AB  - The light-attenuating effects of enamel on the mechanical properties of light
      cured composite resins were evaluated using simple experimental filters. Three
      filters were designed to simulate the light transmittance characteristics of 0.5,
      1.0, and 1.5 mm thick human enamel. The Knoop hardness numbers (KHN) and the
      elastic modulus in transverse tests for twelve shades of three light-cured
      composite resins were examined. These resins were cured either using direct
      irradiation with a light source, or indirect irradiation through one of the
      filters. The attenuations of light by 0.5, 1.0, and 1.5 mm thick enamel filter
      were 45%, 67% and 81% in the 430 nm-550 nm wavelength region, respectively. For
      all materials, KHN and the elastic modulus of specimens irradiated through
      filters were significantly lower than those irradiated directly. The results
      suggest that the light-attenuating effect of enamel reduces the mechanical
      properties of light-cured resin, and may cause poor clinical longevity of
      restorations.

PMID- 12238782
TI  - The effects of particulate metals on cell viability of osteoblast-like cells in
      vitro.
AB  - Effects of fifteen particulate objects, fourteen metals and one non-metal on cell
      viability of osteoblast-like cells were studied in vitro, to determine whether an
      adverse effect on cells could be induced by the particulate form or soluble ions.
      The Al, Ti, Zr, Nb, Ta, Cr, Mo, and Fe particulates depressed cell viability at
      higher particulate concentrations, but their extracts yielded no effect on cells
      except for Mo. On the other hand, little difference in cell viability between
      particulates and extracts was observed for Cu, Si, V, W, and Co. However, Mn and
      Ni yielded more adverse effects on cells in the case of the particulates than the
      extracts. These findings suggested that the effects of particulates on cells
      depended upon the direct effects of contact between particulates and cells, the
      indirect effects of dissolved ions and the kinds of particulate elements.

PMID- 12238785
TI  - Surface-layer modification of hydroxyapatite ceramic with acid and heat
      treatments.
AB  - The purpose of this study was to examine or characterize the surface layer of a
      calcium phosphate ceramic with a gradual compositional change from alpha
      tricalcium phosphate (alpha-TCP) on the surface to hydroxyapatite (HAP) on the
      inside. The surface of a dense HAP ceramic was acid-treated for 1 hour with
      orthophosphoric acid (H3PO4) solutions of several concentrations (0.5, 1.0 and
      5.0 mol/L) or a buffered solution (pH 4.0) consisting of phosphate solutions.
      After acid treatment, specimens were heat-treated at 1,250 degrees C for 1 hour.
      X-ray photoelectron spectroscopy revealed that the compositional gradient layer
      could be modified on the surface of the HAP ceramic with all acid and heat
      treatments, and that 5.0 mol/L H3PO4 solution and heat treatments had a maximal
      thickness of approximately 2 microm for the surface-modified layer. It was
      confirmed that the outermost layer of HAP ceramics modified with the treatments,
      except 5.0 mol/L H3PO4 solution, showed a compound such alpha-TCP.

PMID- 12238784
TI  - Surface treatment agent for dental metals using a thiirane monomer and a
      phosphoric acid monomer.
AB  - To develop a new surface treatment agent which improves the bond strength of
      adhesive resin to both non-precious and precious metals, experimental treatment
      agents containing both an adhesive bonding promoter for precious metals and one
      for non-precious metals were prepared by dissolving epithioalkyl methacrylate
      (EP3MA or EP8MA) and 10-methacryloyloxydecyl dihydrogen phosphate (MDP) in
      acetone. The surfaces of dental metals were treated by the treatment agents and
      metal specimens were butt-jointed together with MMA-PMMA resins. After 2,000
      thermal cyclings in water at temperatures of 4 and 60 degrees C, tensile bond
      strengths were measured. The effectiveness of surface treatments was evaluated by
      tensile bond strengths and microscopic failure mode analysis after the tensile
      test. The combined treatment of EP3MA-MDP or EP8MA-MDP was used effectively for
      non-precious metals as well as precious metals, and was shown to be extremely
      effective compared with the single treatment of EP3MA, EP8MA, or MDP.

PMID- 12238786
TI  - Development of metal-resin composite restorative material. Part 4. Flexural
      strength and flexural modulus of metal-resin composite using Ag-In alloy
      particles as filler.
AB  - The flexural strength and flexural modulus of an experimental metal-resin
      composite, which used Ag-In alloy particle as the filler, were evaluated. The
      effect of acid treatment and heat treatment on the Ag-In alloy particle was
      investigated. The flexural strength of the experimental metal-resin composites
      ranged from 65.5 MPa to 91.0 MPa. The flexural strength of the metal-resin
      composite increased with the temperature of the heat treatment until 350 degrees
      C, but its effect varied with the concentrations of HCl of the acid treatment. A
      metal-resin composite, which used acid-treated and 350 degrees C heat-treated Ag
      In alloy fillers, matched the requirement of strength of ISO 4049. The average of
      flexural modulus of the experimental metal-resin composite was 9.1 GPa. The
      flexural modulus of the metal-resin composite did not vary with the treatment
      conditions of the metal filler. The flexural modulus of a metal-resin composite,
      which used Ag-In alloy particle as the filler, was lower than that of Ag-Sn alloy
      metal-resin composite, which was reported previously. However, the flexural
      strength of the Ag-In alloy metal-resin composite was similar to that of Ag-Sn
      alloy metal-resin composite. We can control a flexural modulus of a metal-resin
      composite without decreasing flexural strength by choosing filler materials.

PMID- 12238787
TI  - Study of resin-bonded calcia investment: part 2. Effect of titanium content on
      the dimensional change of the investment.
AB  - In the present study, titanium powder was chosen as an expanding agent of an
      experimentally prepared resin-bonded calcia investment. The effect of Ti content
      on the dimensional change was investigated. In addition, the effects of the
      heating rate and heating temperature on the dimensional change of the investment
      were investigated during setting and after heating. The expansion increased with
      Ti content and the highest expansion (1.57%+/-0.58) was obtained at 10 mass% Ti.
      The highest expansion was obtained at 900 degrees C for 30 min heating and was
      independent of the heating rate. These findings mean that the titanium powder in
      the calcia investment oxidized sufficiently at that heating condition. It was
      found that the developed resin-bonded calcia investment was able to compensate
      for casting shrinkage of pure titanium by adding some Ti powder to the
      investment.

PMID- 12238788
TI  - Thermal and pH changes, and dimensional stability in irreversible hydrocolloid
      impression material during setting.
AB  - Present study the relation between pH, thermal changes and dimensional stability
      during setting of irreversible hydrocolloid impression materials was
      investigated. Ten specimens of each product were prepared for different
      measurements: Thermal, pH changes and dimensional stability (mass and linear).
      Thermal and pH readings for 20 min and dimensional measurements for a 2 hr period
      were taken after mixing. It was observed that pH and thermal values changed in
      relation to different materials, while they did not change with the time
      according to variance analysis results. On the other hand, dimensional stability
      showed significant differences with time in all tested impression materials. A
      continuous pH change was observed with the time of gelation in all irreversible
      hydrocolloid impression materials tested. Dimensional stability also showed
      significant differences with time in all impression material and as a result
      hydrocolloids with a high pH showed better dimensional stability than those with
      a low pH.

PMID- 12238789
TI  - Effect of tubule orientation and dentin location on the microtensile strength of
      bovine root dentin.
AB  - To investigate the mechanical properties of root dentin and to further clarify
      the cause of vertical root fracture (VRF), this study evaluated the effect of
      tubule orientation (parallel, perpendicular and oblique to the cross-section of
      dumbbell specimens in microtensile tests) and dentin location (cervical, middle,
      and apical location of the root) on the microtensile strength of bovine root
      dentin. Each specimen was stressed in tension at a crosshead speed of 1.0 mm/min.
      The results of the microtensile strength measurements were statistically analyzed
      with one-way ANOVA and the Fisher PLSD. The oblique group (95.18+/-23.80 MPa) was
      significantly (p<0.01) higher than the parallel group (38.93+/-5.28 MPa) or the
      perpendicular group (32.64+/-4.69 MPa). There were no significant differences
      among the different dentin locations within the parallel group (p>0.05). It was
      clarified that the VRF occurs frequently in practical situations due to the
      tubule orientation of root dentin.

PMID- 12238790
TI  - Effects of fluoride and dissolved oxygen concentrations on the corrosion behavior
      of pure titanium and titanium alloys.
AB  - The effects of dissolved-oxygen concentration and fluoride concentration on the
      corrosion behaviors of commercial pure titanium, Ti-6Al-4V and Ti-6Al-7Nb alloys
      and experimentally produced Ti-0.2Pd and Ti-0.5Pt alloys were examined using the
      corrosion potential measurements. The amount of dissolved Ti was analyzed by
      inductively coupled plasma mass spectroscopy. A decrease in the dissolved-oxygen
      concentration tended to reduce the corrosion resistance of Ti and Ti alloys. If
      there was no fluoride, however, corrosion did not occur. Under low dissolved
      oxygen conditions, the corrosion of pure Ti and Ti-6Al-4V and Ti-6Al-7Nb alloys
      might easily take place in the presence of small amounts of fluoride. They were
      corroded by half or less of the fluoride concentrations in commercial
      dentifrices. The Ti-0.2Pd and Ti-0.5Pt alloys did not corrode more, even under
      the low dissolved-oxygen conditions and a fluoride-containing environment, than
      pure Ti and Ti-6Al-4V and Ti-6Al-7Nb alloys. These alloys are expected to be
      useful as new Ti alloys with high corrosion resistance in dental use.

PMID- 12238791
TI  - Durability of bactericidal activity in electrolyzed neutral water by storage.
AB  - Electrolyzed strong and weak acid waters have been widely used for sterilization
      in clinical dentistry because of their excellent bactericidal activities.
      Electrolyzed neutral water was recently developed with a new concept of long-term
      good durability in addition to the excellent bactericidal activity similar to
      acid waters. The present study, evaluated the storage life of this water compared
      with the acid waters in terms of the changes in pH, oxidation-reduction potential
      (ORP), residual chlorine and bactericidal activity under several conditions using
      Staphylococcus aureus 209P. The strong acid water showed a rapid deterioration of
      its bactericidal activity. The weak acid and neutral waters exhibited excellent
      durability. Although all the bacteria were annihilated by the contact with the
      waters even stored for 40 days in the uncapped bottle, the neutral water was
      superior in further long-term duration.

PMID- 12238792
TI  - Initiating committal proceedings "just in case" with voluntary patients: a
      critique of nursing practice.
AB  - Voluntary patients entering mental health units retain the right to accept or
      refuse treatment, including ongoing admission, as they see fit. However the
      nature of acute mental distress means that some patients have fluctuations in
      their mental status and competency to make informed decisions. Inpatient mental
      health nurses face the ongoing challenge of practising in a way that balances the
      requirement to support and promote the autonomy of voluntary patients with the
      need, occasionally, to take actions which although they may appear paternalistic
      are needed to protect those patients or other people. Anecdotal evidence together
      with a clinical audit undertaken by the authors suggest that the practice of
      nurses requesting that doctors sign medical certificates which are then placed on
      patients' files 'just in case' they are needed has become a mechanism by which a
      minority of nurses deal with such challenges. A conceptual analysis of these
      issues indicates that such a practice is both legally questionable and ethically
      inappropriate. We suggest an alternative framework for practice that is legally
      and ethically preferable for both nurses and patients.

PMID- 12238793
TI  - The first nurse practitioner in New Zealand.

PMID- 12238794
TI  - Leadership development: supporting nursing in a changing primary health care
      environment.
AB  - New organisations to provide primary health care in New Zealand are evolving in
      response to changes in policy, funding and contracting arrangements. The premise
      of this paper is that involvement of nurses in the decision-making of health
      organisations is essential to maximise the contribution of nurses and thereby
      promote positive client outcomes. It is argued that development of key leadership
      skills will enable nurses to become more critically aware of underlying power
      structures in the health system and to move towards being acknowledged as
      interdependent health professionals in the Primary Health Organisations (PHOs).
      The particular competencies discussed are those proposed by Van Maurik (1997)
      namely ability to understand and manage organisational politics, work
      facilitatively with people and circumstances, and build a feeling of purpose.

PMID- 12238795
TI  - Advanced nursing practice--evolution or revolution?
AB  - This article has been written to challenge the seemingly unquestioning acceptance
      of changing roles in New Zealand nursing. It is evident in nursing history that a
      number of issues, such as community versus hospital services and generalist
      versus specialist practice, tend to resurface in a cyclic manner. Characteristics
      that are currently associated with 'advanced' nursing roles can be recognised
      when the origins and development of nursing in New Zealand are traced. This gives
      rise to speculation that changes to nursing scope of practice are not so much
      revolutionary as evolutionary, and can perhaps be viewed as a reclaiming rather
      than a redefining of nursing roles.

PMID- 12238796
TI  - Discourse analysis--making connections between knowledge and power: an interview
      with Debbie Payne by Lynne S. Giddings and Pamela J. Wood.
AB  - Discourse analysis is a relative newcomer to the variety of qualitative research
      methodologies used in nursing and midwifery research in Aotearoa/New Zealand.
      This is the seventh article in a series based on interviews with nursing and
      midwifery researchers, designed to offer the beginning researcher a first-hand
      account of the experience of using particular methodologies. This article focuses
      on discourse analysis as interpreted by Debbie Payne (RGON, MA [Hons]) in
      interview. Debbie has recently finished her PhD thesis (submitted for
      examination) and is a Senior Lecturer at the Auckland University of Technology.
      For her thesis Debbie used Foucauldian discourse analysis to explore the use of
      the term 'elderly primigravida' to describe mothers who are pregnant for the
      first time when aged 35 years or over.

PMID- 12238797
TI  - Intramuscular injection angle: evidence for practice?
AB  - This article presents the findings of a search for evidence to support the 45-60
      degree angle of insertion for intramuscular injection of vaccine which is
      recommended in New Zealand. With the objective of discovering the evidence base
      for an intramuscular injection angle which differs from that recommended by the
      World Health Organisation and the accepted practice experienced by the author in
      the UK, Canada, Malawi and the USA, a comprehensive library and internet
      literature search was undertaken. As well, information was sought by personal
      correspondence and contact with a range of immunisation specialists. Both the
      literature specifically on needle angle and that which includes needle angle
      within a wider investigation of technique is included. Overwhelmingly the
      evidence supports a 90 degree angle of needle insertion for intramuscular
      injection as being that most effective in terms of patient comfort, safety and
      efficacy of vaccine.

PMID- 12238798
TI  - Needle angle when giving i.m. vaccinations.

PMID- 12238799
TI  - Submucous implant of abrasive dental materials in rat tongues: clinical and
      histological evaluation.
AB  - This study evaluated the clinical and histological manifestations produced by the
      submucuous implant of abrasive dental materials in the rat tongue. A total of 128
      rats were divided into 4 groups of 32 rats each, according to the material
      selected for the implant: Herjos-F prophylactic paste both in its normal
      composition as well as lacking its abrasive components, SS White pumice stone and
      the abrasive powder of the 3M finishing and polishing sandpaper. The specimens
      were submitted to clinical and histological analyses at 30, 60, 90 and 120 days.
      After 90 days, the formation of nodular lesions in animals implanted with
      materials containing abrasive substances was observed. Histologically, these
      materials produced marked chronic granulomatous reactions. Herjos-F prophylactic
      paste produced the greatest reaction. However, without the abrasive components,
      this paste caused the mildest tissue reactions, with no inflammatory response,
      that was seen in a progressively greater number of cases after 90 days.

PMID- 12238800
TI  - Does LLLT stimulate laryngeal carcinoma cells? An in vitro study.
AB  - Low level laser therapy (LLLT) has been used successfully in biomedicine and some
      of the results are thought to be related to cell proliferation. The effects of
      LLLT on cell proliferation is debatable because studies have found both an
      increase and a decrease in proliferation of cell cultures. Cell culture is an
      excellent method to assess both effects and dose of treatment. The aim of this
      study was to assess the effect of 635nm and 670 nm laser irradiation of H.Ep.2
      cells in vitro using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium
      bromide). The cells were obtained from squamous cell carcinoma (SCC) of the
      larynx and were routinely processed from defrost to the experimental condition.
      Twenty-four hours after transplantation the cells were irradiated with doses
      ranging from 0.04 to 0.48J/cm2 for seven consecutive days (5 mW diode lasers:
      635nm or 670 nm, beam cross-section approximately 1 mm) at local light doses
      between 0.04 and 0.48 J/cm2. The results showed that 635nm laser light did not
      significantly stimulate the proliferation of H.Ep.2 cells at doses of 0.04 J/cm2
      to 0.48 J/cm2, However, 670nm laser irradiation led to an increased cell
      proliferation when compared to both control and 635nm irradiated cells. The best
      cell proliferation was found with 670nm laser irradiated cultures exposed to
      doses of doses of 0.04 to 0.48 J/cm2. We conclude that both dose and wavelength
      are factors that may affect cell proliferation of H.Ep.2 cells.

PMID- 12238801
TI  - Mechanism of action of sodium hypochlorite.
AB  - The choice of an irrigating solution for use in infected root canals requires
      previous knowledge of the microorganisms responsible for the infectious process
      as well as the properties of different irrigating solutions. Complex internal
      anatomy, host defenses and microorganism virulence are important factors in the
      treatment of teeth with asymptomatic apical periodontitis. Irrigating solutions
      must have expressive antimicrobial action and tissue dissolution capacity. Sodium
      hypochlorite is the most used irrigating solution in endodontics, because its
      mechanism of action causes biosynthetic alterations in cellular metabolism and
      phospholipid destruction, formation of chloramines that interfere in cellular
      metabolism, oxidative action with irreversible enzymatic inactivation in
      bacteria, and lipid and fatty acid degradation. The aim of this work is to
      discuss the mechanism of action of sodium hypochlorite based on its antimicrobial
      and physico-chemical properties.

PMID- 12238802
TI  - Activity of endodontic antibacterial agents against selected anaerobic bacteria.
AB  - The antimicrobial activity of substances used as antibacterial agents (solutions
      of 10% calcium hydroxide, camphorated paramonochlorophenol - PMCC, 2%
      chlorhexidine digluconate and 10% castor oil plant detergent) on anaerobic
      bacteria (Fusobacterium nucleatum ATCC 25586, Prevotella nigrescens ATCC 33563,
      Clostridium perfringens ATCC 13124 and Bacteroidesfragilis ATCC 25285), using a
      broth dilution technique, was evaluated in vitro. For determination of minimum
      inhibitory and minimum bactericide concentrations (MIC and MBC), two culture
      broths, Reinforced Clostridial Medium (RCM) and supplemented Brucella,
      standardized inoculum and serially diluted solutions were used. All antibacterial
      agents presented antimicrobial activity that varied for different bacteria. There
      were no differences in the performance of the two broths. Chlorhexidine
      digluconate was the most effective, with the lowest MICs, followed by castor oil
      detergent, PMCC and calcium hydroxide. C. perfringens and B. fragilis were the
      most resistant bacteria to all agents.

PMID- 12238803
TI  - Evaluation of the effect of EDTA, EGTA and CDTA on dentin adhesiveness and
      microleakage with different root canal sealers.
AB  - The effect of chelating solutions EDTA, EGTA and CDTA on human dentin
      adhesiveness and microleakage with 4 sealers (Sealer 26, Sealapex, N-Rickert and
      Endofill) was evaluated in vitro. Whether or not there was a mathematical
      correlation between the tests of adhesiveness and microleakage was also
      evaluated. A total of eighty maxillary and mandibular molars were used to test
      adhesiveness. After wearing of the occlusal surface to obtain a flat surface, the
      sealer was placed with an aluminum cylinder (10 mm x 6 mm). Adhesiveness was
      evaluated with a 4444 Instron universal testing machine. Microleakage was
      evaluated in 160 maxillary canines after root canal instrumentation, obturation
      and clearing. The penetration of India ink in the apical region was measured with
      a measurescope. The teeth were divided into 4 groups: group 1, distilled water,
      group 2, EDTA; group 3, EGTA; group 4, CDTA. Sealer 26 and EDTA had the best
      results (p<0.01) for adhesiveness and microleakage. There was no correlation
      between the test for adhesiveness and microleakage.

PMID- 12238804
TI  - Dentofacial morphology of mouth breathing children.
AB  - The relationship between dentofacial morphology and respiration has been debated
      and investigated from various approaches. The aim of this study was to verify the
      skeletal and dental relationship of mouth and nose breathing children. Thirty
      five children, 7 to 10 years of age, were submitted to orthodontic and
      otorhinolaryngologic evaluations and were separated into 2 groups: 15 nose
      breathers and 20 mouth breathers. Each subject underwent a cephalometric
      radiograph analysis. Statistical analysis (Mann-Whitney U test) indicated that
      changed mode of breathing was associated with 1) maxillo-mandibular retrusion in
      relation to the cranial base in the mouth breathers; 2) the SNGoGn and NSGn
      angles were greater in the mouth breathing group; 3) incisor inclination in both
      jaws and the interincisal angle were not different between groups. There was no
      statistically significant difference in the maxillary and mandibular molar
      heights between the nose breathers and mouth breathers.

PMID- 12238805
TI  - Effectiveness of teaching methods for toothbrushing in preschool children.
AB  - Three different methods of instruction and motivation were used to assess the
      learning process and ability of preschool children in performing toothbrushing.
      Forty children from a private nursery of Brasilia, DF, Brazil, were divided into
      2 groups according to age (3-4 years old and 5-6 years old). The following
      methods of instruction and reinforcement were applied: I--audiovisual; II--child
      as a model; III--individual instruction. Professional prophylaxis was then
      performed and the children remained 48 hours without any kind of oral hygiene.
      Plaque disclosing and plaque index were carried out and recorded. The children
      subsequently brushed their teeth according to each method of instruction and a
      new plaque index was recorded. The data were analyzed statistically using the
      Student t-test and the comparison of two proportions. The results showed that the
      children of both groups reduced plaque index and that the individual instruction
      method was superior (p<0.05) to the others at all ages. Children older than 5
      years of age were able to learn and accomplish toothbrushing better than younger
      children.

PMID- 12238806
TI  - Bilateral fusion of mandibular second molars with supernumerary teeth: case
      report.
AB  - Fusion is a developmental anomaly characterized by the union of two adjacent
      teeth. In this article we report a rare case of bilateral fusion of permanent
      mandibular second molars with supernumerary teeth. The rarity with which this
      entity appears, along with its complex characteristics, often make it difficult
      to treat. The endodontic management of one tooth is described, as well as the
      successful treatment of a periradicular lesion.

PMID- 12238807
TI  - Replica of human dentin treated with different desensitizing agents: a
      methodological SEM study in vitro.
AB  - This is a preliminary study to determine a methodological sequence in vitro which
      may allow the reproduction of dentin for SEM analysis, after the use of different
      desensitizing agents. Dentin discs obtained from extracted human third molars
      were etched with 6% citric acid, an artificial smear layer was created and the
      surface dentin discs were divided into four quadrants. Quadrants 2, 3 and 4 of
      each disc were conditioned with 6% citric acid. The desensitizing agents (Oxa
      Gel, Gluma Desensitizer and an experimental agent) were applied to quadrants 3
      and 4. To evaluate the acid resistance of the treatment, quadrant 4 was etched
      again with 6% citric acid. An impression was then taken with Aquasil ULV. After a
      setting period of 6 min, each disc was removed from the impression and stored in
      a moist-free environment for 24 h at 37 degrees C. After that time, a low
      viscosity epoxy resin (Araltec GY 1109 BR) was poured into the impression and
      cured for 24 h. All specimens were metal-coated for SEM analysis. Comparison of
      the photomicrographs of dentin discs with their respective impressions and resin
      replicas showed that this technique can reproduce the characteristics of the
      dentin surface treated with desensitizing agents.

PMID- 12238808
TI  - Comparative study of tissue response to polyglecaprone 25, polyglactin 910 and
      polytetrafluorethylene suture materials in rats.
AB  - The authors evaluated the biocompatibility of three suture materials,
      polyglecaprone 25, polyglactin 910 and polytetrafluorethylene, implanted into
      subcutaneous tissue in the dorsal region of 20 Wistar albinus rats. After periods
      of 2, 7, 14 and 21 days, the rats were sacrificed and the specimens were
      processed for routine histotechnical analysis and stained with hematoxylin and
      eosin. The rate of fibrosis, angioblastic and fibroblastic proliferation, and
      also the intensity of inflammation were observed with the optic microscope. The
      results showed that polyglecaprone 25 suture material induced a mild inflammatory
      reaction, followed by polyglactin 910 and polytetrafluorethylene, respectively.
      Such biological behavior must be considered during the selection of the suture
      material to be used in oral surgery.

PMID- 12238809
TI  - Histometric study of socket healing after tooth extraction in rats treated with
      diclofenac.
AB  - The purpose of the present study was to investigate if diclofenac administration
      interferes with the time course of alveolar wound healing in rats. Forty-two
      Wistar rats were used, 21 rats received 10 mg/kg/day of diclofenac one day before
      and 4 days after extraction of the right maxillary incisors and 21 rats received
      saline. The animals were sacrificed 7, 14 and 21 days after tooth extraction.
      Progressive new bone formation and a decrease in the volume fraction of blood
      clot and connective tissue from 1 to 3 weeks after tooth extraction was
      quantified using the histometric point-counting method. Diclofenac treatment
      caused a significant delay in new bone formation in association with an
      impairment of blood clot remission/organization.

PMID- 12238810
TI  - Expression and activity of matrix metalloproteinase-2 (MMP-2) in the development
      of rat first molar tooth germ.
AB  - Tooth germ development is associated with morphological and biochemical changes
      of the dental papilla and enamel organ. Enzymes with gelatinolytic activities
      were studied by semiquantitative reverse transcriptase-polymerase chain reaction
      (RT-PCR) and enzymography in tooth germ of newborn to 15-day-old rats. Three
      major bands with gelatinolytic activity were detected at all periods and
      characterized as the latent and active forms of MMP-2 using their molecular
      weight and activity dependent on Zn++ and Ca++ ions as criteria. Expression and
      activity of MMP-2 increased progressively from 0 to 15 days after birth.
      Mechanical separation of the tooth germ from 10-day-old rats showed that the
      gelatinolytic activity was localized mainly in the dental papilla and not the
      dental organ. These data indicate that the expression and activity of MMP-2
      varies during the development and maturation of rat first molar tooth germ.

PMID- 12238811
TI  - Direct measurement of the association constant of HER2/neu antisense
      oligonucleotide to its target RNA sequence using a molecular beacon.
AB  - A molecular beacon approach was developed to directly determine the association
      constant of RNA-DNA hybrid formation. The molecular beacon was composed of a 15
      nt loop structure containing the antisense sequence that can hybridize with the
      AUG translational start site of the HER2/neu gene, which is overexpressed in a
      significant proportion of breast, ovarian, and lung tumors. The equilibrium
      association constant (Ka) of DNA binding to the RNA oligonucleotide was 6.4 +/-
      0.14 x 10(7) M(-1) in the presence of 150 mM NaCl at 22 degrees C. The free
      energy change (AG) associated with RNA-DNA hybrid formation was -10.7 kcal/mole.
      The melting temperature (Tm) of RNA-DNA hybrid was 64.4 degrees C +/- 1 degree C
      in the presence of 150 mM NaCl. The RNA-DNA hybrid was more stable than the
      corresponding DNA-DNA duplex in 150 mM NaCl, as judged by both Ka and Tm data. We
      also determined the Ka, deltaG, and Tm values of RNA-DNA and DNA-DNA duplex
      formation in the presence of three monovalent cations, Li+, K+, and Cs+. The
      feasibility of this method was also investigated using a phosphorothioate
      molecular beacon. The information generated through this new approach for
      thermodynamic measurements might be useful for the design of oligonucleotides for
      antisense therapeutics.

PMID- 12238812
TI  - Nuclear extracts promote gene correction and strand pairing of oligonucleotides
      to the homologous plasmid.
AB  - We compared strand pairing and gene correction activities between different
      constructs of oligonucleotides, using homologous supercoiled DNA and eukaryotic
      nuclear extracts. The RNA-DNA chimeric oligonucleotide was more efficient in
      strand pairing and gene correction than its DNA-DNA homolog. Single-stranded
      deoxyoligonucleotides showed similar strand pairing and correction activity to
      the modified RNA-DNA chimeric oligonucleotides, whereas single-stranded
      ribooligonucleotides did not show either activity. However, the correlations were
      not always linear, suggesting that only a fraction of the joint molecules may be
      processed to cause the final gene correction. Several mammalian extracts with
      markedly different in vitro activity showed the similar amounts of the joint
      molecules. These results led us to conclude that strand pairing is a necessary
      event in gene correction but may not be the rate-limiting step. Furthermore,
      depletion of HsRad51 protein caused large decreases in both strand-pairing and
      functional activities, whereas supplementation of HsRad51 produced only a slight
      increase in the repair activity, indicating that HsRad51 participates in the
      strand pairing, but subsequent steps define the frequency of gene correction. In
      addition, we found that the structure and stability of intermediates formed by
      single-stranded deoxyoligonucleotides and RNA-DNA chimeric oligonucleotides were
      different, suggesting that they differ in their mechanisms of gene repair.

PMID- 12238813
TI  - Increase in therapeutic index of doxorubicin and vinblastine by aptameric
      oligonucleotide in human T lymphoblastic drug-sensitive and multidrug-resistant
      cells.
AB  - Aptameric GT oligomers are a new class of potential anticancer molecules that
      inhibit the growth of human cancer cell lines by binding to specific nuclear
      proteins. We demonstrated that an aptameric GT oligonucleotide increased the
      therapeutic index of doxorubicin and vinblastine in T lymphoblastic drug
      sensitive and multidrug-resistant (MDR) cells. The doxorubicin ID50 decreased 6.5
      fold by coadministration of 1 microM GT to CCRF-CEM cells and by 24-fold by
      coadministration of 0.75 microM GT to CEM-VLB300 cells. In CEM-VLB300 cells, the
      vinblastine ID50 decreased 11-fold by coadministration of 0.5 microM GT. Control
      CT sequence did not potentiate the drugs in either CCRF-CEM or CEM-VLB300 cells.
      The ability of GT to bind to specific nuclear proteins in cancer cells related to
      the increase in the therapeutic index of doxorubicin and vinblastine. No
      cooperation was detected by the administration of GT oligomer together with
      doxorubicin to rat differentiated thyroid FRTL-5 cells and to normal human
      lymphocytes. These cells did not show binding of GT to the specific nuclear
      proteins, and they were not sensitive to the cytotoxic action of the GT sequence.
      Drug potentiation by GT not involving normal human lymphocytes might be exploited
      to develop a more selective treatment of drug-sensitive and MDR tumors.

PMID- 12238814
TI  - Intracellular inhibition of hepatitis B virus S gene expression by chimeric DNA
      RNA phosphorothioate minimized ribozyme.
AB  - Chronic hepatitis B virus (HBV) infection is a major problem in Asia. Current
      therapies for chronic hepatitis B have limited efficacy. The successful use of
      ribozymes for intracellular inhibition of HBV gene expression was recently
      reported. As an alternative to ribozymes, the use of DNA-containing,
      phosphorothioate-modified, minimized hammerhead ribozymes (minizymes) to inhibit
      hepatitis B surface antigen (HBsAg) expression and viral replication was
      investigated. Such molecules can be synthesized and supplied exogenously. Two
      conserved sites within the HBsAg open reading frame (ORF) were targeted. PLC/PRF5
      cells or 2.2.15 cells were treated with minizymes or antisense oligomers to
      assess the effects on cell viability, HBsAg expression, and viral DNA production.
      Treatment with the minizyme, MZPS1, resulted in >80% inhibition of HBsAg
      expression in PLC/PRF5 cells. MZPS1 had more inhibitory effect than the antisense
      oligonucletoide target at the same region, whereas the control minizyme had
      little effect. Another gene-specific minizyme, MZPS2, did not show any effect.
      Treated cells remained fully viable. Treatment of 2.2.15 cells with MZPS1 also
      led to decreased HBsAg expression. In addition, a 2.3-fold decrease in viral
      production was observed. Our data showed that minizymes can inhibit HBV gene
      expression and may potentially be useful for clinical therapy against chronic HBV
      infection.

PMID- 12238815
TI  - In vitro selection of DNA aptamers against the HIV-1 TAR RNA hairpin.
AB  - In vitro selection was performed to identify DNA aptamers against the TAR RNA
      stem-loop structure of HIV-1. A counterselection step allowed the elimination of
      kissing complex-forming aptamers previously selected (Boiziau et al. J. Biol.
      Chem. 1999; 274:12730). This led to the emergence of oligonucleotides, most of
      which contained two consensus sequences, one targeted to the stem 3'-strand (5'
      CCCTAGTTA) and the other complementary to the TAR apical loop (5'-CTCCC). The
      best aptamer could be shortened to a 19-mer oligonucleotide, characterized by a
      dissociation constant of 50 nM. A 16-mer oligonucleotide complementary to the TAR
      stem 3'-strand could also be derived from the identified aptamers, with an equal
      affinity (Kd = 50 nM). Experiments performed to elucidate the interaction between
      TAR and the aptamers (UV melting measures, enzymatic and chemical footprints)
      demonstrated that the TAR stem 5'-strand was not simply displaced as a result of
      the complex formation but unexpectedly remained associated on contact with the
      antisense oligonucleotide. We suggest that a multistranded structure could be
      formed.

PMID- 12238816
TI  - Comparative analysis of antisense RNA, double-stranded RNA, and delta ribozyme
      mediated gene regulation in Toxoplasma gondii.
AB  - RNA tools, namely, antisense RNA, double-stranded RNA (dsRNA), and delta
      ribozyme, were comparatively analyzed for the development of effective RNA-based
      gene modulators. The gene encoding uracil phosphoribosyltransferase (UPRT) of
      Toxoplasma gondii was used as a target and a negative selectable marker. Using
      plasmid transformation and drug selection assays, we obtained T. gondii
      transformants resistant to 5-fluoro-2'-deoxyuridine (FDUR), the cytotoxic prodrug
      and substrate of UPRT, when the plasmids expressing dsRNA and active delta
      ribozyme were used. No resistant transformants were detected when the plasmids
      carrying the antisense RNA, the inactive delta ribozyme, or the chloramphenicol
      acetyltransferase (CAT) genes were used. Parasites generated using the plasmids
      expressing dsRNA and the delta ribozyme become resistant to FDUR with an LD50 of
      50 +/- 5 microM and 25 +/- 8 microM, respectively. These values are approximately
      25-fold and 12-fold higher than that of the RH parental parasite strain,
      indicating that UPRT activity of the transformed parasites was drastically
      inhibited. Using Northern and Southern blot analysis, we demonstrated that dsRNA
      and the delta ribozyme interrupt the expression of UPRT. These two RNA tools
      should, thus, be very useful for the study of gene expression.

PMID- 12238817
TI  - A rapid and simple nonradioactive method for in vitro testing of ribozyme
      activity.
AB  - Ribozymes that target specific messenger RNA transcripts are powerful tools in
      the emerging fields of functional genomics, proteomics, and metabolomics. We have
      found that successful in vitro testing greatly increases the likelihood of
      producing ribozymes with good efficacy in living cells. A rapid and simple
      nonradioactive method for systematic in vitro testing of ribozyme-cleaving
      activity is reported. Ribozymes are synthesized enzymatically from double
      stranded DNA (dsDNA) oligonucleotides without vector cloning. Substrate target
      DNA template is cloned into a vector flanked with SP6 and T7 promoters at
      multiple cloning sites that permit colorimetric screening and ampicillin
      selection, enhancing the efficiency of the cloning procedure. Ribozyme cleavage
      products are satisfactorily resolved on 2.0% NuSieve 3:1 agarose (FMC Products,
      Rockland, ME)/formaldehyde gels by electrophoresis. This method avoids the
      preparation of polyacrylamide gels. Using this procedure, the ribozyme, target
      substrate RNA, and ribozyme cleavage products are all easily detected by ethidium
      bromide staining. Resolution and detection are fast and simple, eliminating the
      need for either polyacrylamide gel analysis or radiolabeling. The use of RNase
      inhibitors in the assays is also assessed and discussed.

PMID- 12238818
TI  - Quality, advocacy, healthcare policy, and the surgeon.

PMID- 12238819
TI  - Aortic root replacement with cryopreserved allograft for prosthetic valve
      endocarditis.
AB  - BACKGROUND Our strategy has been to treat aortic prosthetic valve endocarditis
      (PVE) with radical debridement of infected tissue and aortic root replacement
      with a cryopreserved aortic allograft. This study examines the effectiveness of
      this strategy on hospital mortality and morbidity, recurrent endocarditis, and
      survival. METHODS: From 1988 through 2000, 103 patients with aortic PVE underwent
      root replacement with a cryopreserved aortic allograft. Abscesses were present in
      78%, and aortoventricular discontinuity was present in 40%. Thirty-two patients
      had at least one previous operation for endocarditis. In 23 patients with a
      history of native valve endocarditis, the allograft was implanted after one
      episode (17 patients), two episodes (5 patients), or three episodes of PVE (1
      patient). In the 80 patients without a history of native valve endocarditis, the
      allograft was placed after one previous aortic valve replacement (57 patients),
      two (19), or three (4) previous aortic valve replacements. Among the 92 patients
      with positive cultures, 52 had staphylococcal organisms, 20 had streptococcal, 6
      had fungal, 4 had gram-negative, and 6 had enterococcal organisms. Mean follow-up
      was 4.3 +/- 2.9 years. RESULTS: Hospital mortality was 3.9%. Permanent pacemakers
      were required in 31 patients. Survival at 1 year, 2 years, 5 years, and 10 years
      was 90%, 86%, 73%, and 56%, respectively, with a risk of 5.3% per year after 6
      months. Four patients underwent reoperation for recurrent PVE of the allograft
      (95% freedom from recurrent PVE at > or = 2 years). Risk of recurrent PVE peaked
      at 9 months and then declined to a low level by 18 months. CONCLUSIONS: A
      strategy of radical debridement and aortic root replacement with a cryopreserved
      aortic allograft for aortic PVE is safe, effective, and recommended.

PMID- 12238820
TI  - Minimally invasive mitral valve surgery: a 6-year experience with 714 patients.
AB  - BACKGROUND: This study analyzes a single institutional experience with minimally
      invasive mitral valve operations of 6 years, reviewing short-term morbidity and
      mortality and long-term echocardiographic follow-up data. METHODS: Seven hundred
      fourteen consecutive patients had minimally invasive mitral valve procedures
      between November 1995 and November 2001; concomitant procedures included 91
      multiple valves and 18 coronary artery bypass grafts. Of these 714 patients, 561
      patients had isolated mitral valve operations (375 repairs, 186 replacements).
      Mean age was 58.3 years (range, 14 to 96 years; 30.1% > 70 years), and 15.4% of
      patients had previous cardiac operations. Arterial cannulation was femoral in
      79.0% and central in 21%, with the port access balloon endo-occlusion used in
      82.3%. Cardioplegia was transjugular retrograde (54.1%) or antegrade (29.4%).
      Right anterior minithoracotomy was used in 96.6% and left posterior
      minithoracotomy in 2.2%. RESULTS: Hospital mortality for primary isolated mitral
      valve repair was 1.1% and 5.8% for isolated mitral valve replacement. Overall
      hospital mortality was 4.2% (30 of 714). Mean cross-clamp time was 92 minutes and
      mean cardiopulmonary bypass time was 127 minutes. Postoperatively, median
      ventilation time was 11 hours, intensive care unit time was 19 hours, and total
      hospital stay was 6 days. Complications for all patients included permanent
      neurologic deficit (2.9%), aortic dissection (0.3%); there was no mediastinal
      infection (0.0%). Follow-up echocardiography demonstrated 89.1% of the repair
      patients had only trace or no residual mitral insufficiency. CONCLUSIONS: This
      study demonstrates that the minimally invasive port access approach to mitral
      valve operations is reproducible with low perioperative morbidity and mortality
      and with late outcomes that are equivalent to conventional operations.

PMID- 12238821
TI  - Results of valve replacement with Omniscience mechanical prostheses.
AB  - BACKGROUND: The Omniscience mechanical valve has been the subject of multiple
      clinical investigations with variable results, including reports of high
      complication and reoperation rates. METHODS: Records of all patients who received
      Omniscience valves were reviewed, and follow-up interviews were conducted to
      determine the incidence of valve-related morbidity, mortality, and functional
      results. Incidence of complications was expressed as events per 100 patient-years
      follow-up. Survival and freedom from valve-related complications and mortality
      were calculated using a product limit method. RESULTS: Between 1984 and 1988, 192
      patients received 213 Omniscience valves [93 mitral (M), 79 aortic (A), and 20
      multiple (D) valve replacements]. Perioperative mortality was 9%. The incidence
      of major valve-related morbidity was as follows: thrombosis, 1.30 M, 0.17 A, 0.72
      D; endocarditis, 0.48 M, 0.18 A, 0 D; hemorrhagic, 4.67 M, 2.84 A, 5.00 D;
      embolic, 2.90 M, 2.27 A, 1.57 D; nonstructural dysfunction, 1.66 M, 1.08 A, 2.27
      D; reoperation, 4.02 M, 1.99 A, 6.48 D. All explanted valves (n = 43) were
      examined, and 40% (n = 17) were found to have limited disc excursion in the
      absence of thrombus. Freedom from valve-related morbidity, mortality, or
      reoperation at 10 years was 22% for mitral, 39% for aortic, and 17% for
      multivalve replacements. At follow-up, only 73% of patients were New York Heart
      Association class I or II. Five- and 10-year estimated survivals were 72% and 55%
      for M, 80% and 51% for A, and 65% and 50% for D replacements. CONCLUSIONS: Use of
      the Omniscience valve provided poor functional improvement and a significant
      incidence of valve-related complications, including the need for reoperation.

PMID- 12238822
TI  - Predictors of postoperative complications in high-risk octogenarians undergoing
      cardiac operations.
AB  - BACKGROUND: Cardiac operations in octogenarians are currently reserved for
      selected patients with severe symptoms and low extracardiac comorbidity; early
      and midterm results are satisfactory. We evaluated the outcome of high-risk
      octogenarians undergoing cardiac operations and investigated the predictors of
      postoperative complications. METHODS: Between June 1998 and March 2001, 73
      consecutive octogenarians (mean age = 83.1 +/- 3.0 years) hospitalized and
      awaiting operation in our Department were analyzed for postoperative
      complications. We recorded the main risk factors for cardiovascular disease,
      symptoms of heart failure, previous myocardial infarction, reoperation, left
      ventricular ejection fraction, use of intraaortic balloon pump, surgical
      priority, and operative risk. Cerebrovascular disease, peripheral vascular
      disease, chronic obstructive pulmonary disease, and renal failure were the
      preoperative extracardiac comorbidities considered. We adopted a
      multidisciplinary approach to perioperative management. RESULTS: Surgical
      procedures included coronary artery bypass grafting in 36 patients (49.3%), valve
      procedures in 20 (27.4%), and combined coronary artery bypass grafting and valve
      procedures in 17 patients (23.3%). In-hospital death occurred in 6 patients
      (8.2%). Twenty-one patients (28.8%) had major postoperative complications
      including renal failure (15.1%), respiratory failure (8.2%), and myocardial
      infarction (8.2%). The main predictors of postoperative complications were New
      York Heart Association functional class IV, Canadian Cardiovascular Society
      angina class 4, and prolonged aortic cross-clamping time. CONCLUSIONS: Cardiac
      operations can achieve satisfactory results even in high-risk octogenarians.
      Early surgical intervention before severe symptoms appear, and a
      multidisciplinary approach to perioperative management, may reduce postoperative
      complications.

PMID- 12238823
TI  - Efficacy and safety of on-pump beating heart surgery for valvular disease.
AB  - BACKGROUND: This study was conducted to assess the efficacy and applicability of
      on-pump beating heart valvular operations using retrograde coronary sinus
      perfusion. METHODS: A prospective, randomized study was conducted. A total of 50
      patients participated in this study after having been allocated to one of two
      groups. On-pump beating heart valvular operations using retrograde coronary sinus
      perfusion as myocardial protection were performed in 25 patients (beating heart
      procedure group: aortic = 8 patients, mitral = 15 patients, double = 2 patients).
      Twenty-five patients underwent conventional valvular operation using retrograde
      continuous warm blood cardioplegia (conventional procedure group: aortic = 9
      patients; mitral = 13 patients; double = 3 patients). The remaining operative
      variables and early outcomes of these procedures were compared. In the beating
      heart procedure group, myocardial tissue oxygen was measured by near infrared
      spectroscopy, and partial oxygen pressure of coronary sinus perfusion was also
      measured. RESULTS: The visual field of the on-pump beating heart was equal to
      that of conventional valvular operation, and technical accuracy was not
      compromised. In the beating heart procedure group, tissue oxygen saturation was
      maintained at 79% +/- 2%, and partial oxygen pressure of coronary sinus perfusion
      blood and returned blood were maintained at 383 +/- 29 mm Hg and 38 +/- 2 mm Hg,
      respectively. Postoperative peak creatine kinase-MB (measured every 3 hours
      postoperatively) and peak troponin T concentrations were significantly lower than
      those of conventional procedures (17.5 +/- 7.8 vs 32.1 +/- 9.3 IU/L and 0.12 +/-
      0.04 vs 0.21 +/- 0.06 ng/mL, respectively; p < 0.05). There was no operative
      mortality and no major complications. CONCLUSIONS: On-pump beating heart valvular
      operation is a good surgical option, and has advantages because conditions for
      the heart are more physiologic with beating tonus than with cardioplegia.

PMID- 12238824
TI  - Stentless xenografts and homografts for right ventricular outflow tract
      reconstruction during the Ross operation.
AB  - BACKGROUND: Shortage of homografts prompted us to replace the transplanted
      pulmonary trunk with stentless xenografts during the Ross procedure. The 5-year
      follow-up in comparison with pulmonary homografts is presented. METHODS: From
      April 1997 to March 2002, of 51 patients undergoing a modified Ross procedure 15
      patients (age range 55 to 65 years, mean 59 +/- 5) received a stentless
      xenograft, and 36 patients (15 to 56 years, mean 36 +/- 11) a pulmonary homograft
      for right ventricular outflow tract (RVOT) reconstruction. Follow-up was complete
      for a mean of 3.1 years (range 6 to 60). Regularly performed echocardiography
      included determination of valve annulus, peak instantaneous gradient, leaflet
      performance, location of obstruction, and degree of regurgitation. RESULTS: There
      was 1 late death and 1 reoperation for homograft stenosis. The homograft annulus
      diameter decreased by a mean of 10% (range 3 to 10 mm; p < 0.01), and peak
      Doppler gradient increased significantly (p < 0.001). All patients except 1 had
      gradients less than 25 mm Hg. Gradients in xenograft patients were stable at a
      low level (6.5 +/- 4.3 mm Hg to 8.8 +/- 7.4 mm Hg at the latest follow-up). Mild
      pulmonary regurgitation was noted in 46.6% (xenografts) and 19.5% (homografts).
      Leaflet quality and mobility were maintained in all patients. CONCLUSIONS:
      Pulmonary homografts underlie a process of annular reduction after the Ross
      procedure, which is usually not associated with graft stenosis. Mild pulmonary
      regurgitation is more common in xenografts than in homografts. RVOT
      reconstruction using stentless xenografts represents a satisfactory treatment
      modality for aged patients.

PMID- 12238825
TI  - In the eye of both patient and spouse: memory is poor 1 to 2 years after coronary
      bypass and angioplasty.
AB  - BACKGROUND: The study aimed to investigate patient and spouse perception of
      cognitive functioning 1 to 2 years after coronary artery bypass grafting.
      METHODS: Seventy-six married patients who had undergone coronary artery bypass
      grafting were selected and sex- and age-matched with 75 concurrent married
      patients who had undergone percutaneous transluminal coronary angioplasty.
      Couples received a letter of explanation and then completed telephone interviews.
      Forty-seven questions assessed memory, concentration, general health, social
      functioning, and emotional state. Response choices were: improved, unchanged, or
      deteriorated function after coronary artery bypass grafting/percutaneous
      transluminal coronary angioplasty. RESULTS: Patients who had undergone coronary
      artery bypass grafting did not differ in subjective ratings on any measure from
      patients who had undergone percutaneous transluminal coronary angioplasty. There
      were no differences between spouses in the respective groups; spouse ratings also
      did not differ from patient ratings. Only in memory function did patients and
      spouses report a postprocedural decline. CONCLUSIONS: No subjective differences
      were found in patients who had undergone either coronary artery bypass grafting
      or percutaneous transluminal coronary angioplasty. Spouse ratings agreed with
      each other and with patient ratings. Positive correlations were found between the
      questionnaire factors, suggesting that perceived health and well-being are
      associated with subjective cognition.

PMID- 12238826
TI  - Acute effects of 17beta-estradiol on left internal mammary graft after coronary
      artery bypass grafting.
AB  - BACKGROUND: Vasospasm of arterial conduits used for coronary surgical procedures
      is an important cause of postoperative graft failure. Mounting experimental
      evidence suggests that estrogen reverses acetylcholine-induced vasospasm of the
      coronary arteries in animals and humans. Estrogen also affects endothelium
      derived constrictor factors. We therefore investigated the in vivo vasomotor
      responses to transdermal 17beta-estradiol of the left internal mammary artery
      (LIMA) grafted on the anterior descending coronary artery. METHODS: We studied 20
      women, mean age of 62 +/- 7.2 years (range, 48 to 73 years), who had undergone
      cardiopulmonary bypass for coronary artery bypass grafting. They received
      transdermal 17beta-estradiol on the fifth day after operation. The diameter,
      cross-sectional area, and blood flow of the LIMA graft were measured by
      transthoracic color Doppler echography before (basal values) and after the
      transdermal administration of 50 microg of 17beta-estradiol (control). RESULTS:
      LIMA graft vasodilation after the administration of 17beta-estradiol was
      observed. A significant increase in diameter (2.06 +/- 0.4 mm versus 2.37 +/-
      0.28 mm; p = 0.035) and cross-sectional area (3.45 +/- 1. 2 mm2 versus 4.24 +/- 1
      mm2; p = 0.039) was registered. The LIMA graft mean flow increased by 49% (44.76
      +/- 27.19 mL/min versus 56.62 +/- 27.69 mL/min), but this increase was not
      statistically significant (p = 0.06). CONCLUSIONS: The acute postoperative
      transdermal administration of 17beta-estradiol induced a significant increase of
      LIMA graft diameter and cross-sectional area in postmenopausal women who
      underwent coronary artery bypass grafting. The LIMA graft vasodilation was also
      associated with an improvement in LIMA blood flow.

PMID- 12238827
TI  - Coronary artery bypass surgery by the transdiaphragmatic approach.
AB  - BACKGROUND: The transdiaphragmatic approach is useful for reoperative coronary
      artery bypass grafting involving the right coronary artery because it does not
      require median sternotomy or cardiopulmonary bypass. METHODS: Twenty-one patients
      underwent coronary artery bypass surgery by the transdiaphragmatic approach. The
      ratio of first operations to reoperations was 7:14. The cause of reoperation was
      occlusion of a saphenous vein graft in 4 patients, right gastroepiploic artery
      graft failure in 3 patients, and a new sclerotic lesion in the right coronary
      artery in 7 patients. When the radial artery or saphenous vein was used, grafting
      extended from the origin of the gastroduodenal artery to the right coronary
      artery. RESULTS: None of the patients died during surgery. The sites of
      anastomoses were as follows: right coronary artery in 11 patients, right
      posterior descending artery in 9 patients, and the atrioventricular node artery
      in 1 patient. The following types of grafts were used: right gastroepiploic
      artery in 17 patients, saphenous vein in 2 patients, and radial artery in 2
      patients. CONCLUSIONS: When reoperative coronary surgery involving the right
      coronary artery is necessary, the transdiaphragmatic technique is effective
      because it does not damage patent grafts placed during the primary operation.

PMID- 12238828
TI  - Bilateral internal thoracic artery grafting: midterm results of composite versus
      in situ crossover graft.
AB  - BACKGROUND: Two common techniques of bilateral internal thoracic artery grafting
      are the composite T graft and in situ crossover graft. The superiority of one
      method over the other has not yet been established. METHODS: From April 1996 to
      July 1999, bilateral skeletonized internal thoracic arteries were used as T
      grafts (composite group, n = 649) and in situ grafts (cross group, n = 351) in
      1,000 consecutive patients. In the cross group, in situ right internal thoracic
      artery was routed anterior to the aorta across the midline for grafting to the
      left anterior descending artery, and the left internal thoracic artery was used
      for the circumflex branches. RESULTS: The two groups had comparable preoperative
      risk profiles. Bypass time and aortic cross-clamping time were longer in the
      composite group (80 +/- 38 and 67 +/- 29 minutes versus 66 +/- 43 and 55 +/- 34
      minutes, respectively). Number of anastomoses per patient was similar (3.1 versus
      3.2). However, more sequential anastomoses were performed in the composite group
      (62% versus 53%), and the gastroepiploic artery was used more often in the cross
      group (30% versus 19%). Thirty-day mortality was 3.9% in the composite and 2.3%
      in the cross group (not significant). Occurrence of postoperative complications
      (sternal infection, myocardial infarction, cerebrovascular accident, and
      bleeding) was similar. Late follow-up (2 to 56 months) showed increased return of
      angina (6% versus 3.1%; p = 0.046) and decreased 4-year survival (Kaplan-Meier;
      86% +/- 2.7% versus 92.4% +/- 1.5%; p = 0.07) in composite patients. CONCLUSIONS:
      Early results of bilateral internal thoracic artery grafting with composite T
      graft are comparable with those of in situ grafts. However, increased angina
      return and decreased midterm survival led us to recommend in situ grafting
      whenever technically possible.

PMID- 12238829
TI  - Early postoperative outcome and medium-term survival in 540 diabetic and 2239
      nondiabetic patients undergoing coronary artery bypass grafting.
AB  - BACKGROUND: An increasing proportion of patients undergoing coronary artery
      bypass grafting (CABG) are diabetics. Patient characteristics, early
      postoperative outcome, and midterm survival in diabetic patients after CABG were
      investigated. METHODS: A total of 2779 consecutive patients undergoing isolated
      CABG during 1995 to 1999 were studied, 19.4% of whom had diabetes mellitus.
      Demographic and peri-procedural data were registered prospectively in a
      computerized institutional database. RESULTS: The diabetic group was younger and
      included a higher proportion of women, and patients with hypertension, triple
      vessel disease, and unstable angina. They required a higher number of bypasses,
      and longer cross-clamp and cardiopulmonary bypass times. Intensive care unit and
      hospital stays were prolonged and the need for inotropic agents,
      hemotransfusions, and dialysis was higher in the diabetic group. Renal failure,
      stroke (4.3% versus 1.7%), mediastinitis, and wound infections were more
      frequently encountered. Thirty-day mortality was 2.6% versus 1.6% (p = 0.15).
      Cumulative 5-year survival was 84.4% versus 91.3% (p < 0.001). CONCLUSIONS: Short
      term mortality was acceptable in diabetic patients after CABG but they had
      increased postoperative morbidity in comparison with nondiabetic patients,
      particularly with regard to renal function, cerebral complications, and
      infections. Midterm survival was impaired in diabetic patients mainly because of
      a less favorable outcome in patients treated with insulin.

PMID- 12238830
TI  - Combination of sotalol and magnesium prevents atrial fibrillation after coronary
      artery bypass grafting.
AB  - BACKGROUND: Atrial fibrillation (AF) is a common complication reported in 20% to
      40% of patients after coronary operations. Sotalol alone and magnesium alone have
      been shown to partially decrease the incidence of AF. The goal of this study was
      to evaluate the efficacy of these two pharmacological agents, used alone or in
      combination, to reduce postoperative AF. METHODS: Two hundred seven consecutive
      coronary artery bypass patients (mean age 62 +/- 11 years) were randomized to
      receive sotalol alone (80 mg twice daily for 5 days starting from the morning of
      the first postoperative day) (group S), magnesium alone (1.5 g daily for 6 days
      starting in the operating room just before cardiopulmonary bypass) (group M),
      both pharmacologic agents at the same dosages (group S+M), or no antiarrhythmic
      agents (group CTR). All patients with an ejection fraction less than 0.40 were
      excluded. RESULTS: The incidence of postoperative AF was 11.8% (6/51) in the S
      group, 14.8% (8/54) in the M group, 1.9% (1/52) in the S+M group, and 38% (19/50)
      in the CTR group. The following differences were significant: group CTR versus
      groups S, M, and S+M with values of p = 0.002, p = 0.007 and p < 0.0001,
      respectively; and group S+M versus groups S and M with p = 0.04 and p = 0.01,
      respectively. CONCLUSIONS: Incidence of AF after coronary operation was
      significantly reduced by the administration of sotalol alone and magnesium alone;
      more importantly, the incidence was further reduced by combining these agents.

PMID- 12238831
TI  - Is there a role for endothelin-blockade early after coronary artery bypass
      grafting?
AB  - BACKGROUND: Diverse results exist regarding myocardial release of endothelin
      after coronary artery bypass grafting. Because endothelin may be involved in
      regulation of coronary blood flow, postoperative endothelin-blockade could
      influence the surgical outcome. In this study, we have evaluated the cardiac
      outflow of endothelin and effects on coronary flow by endothelin-blockade
      immediately after completion of the coronary bypass grafting. METHODS: Thirty
      patients were subjected to infusions of endothelinA blocker (BQ-123, 260 nmoL/min
      for up to 30 minutes) or endothelinA blocker and endothelinB blocker (BQ-123 and
      BQ-788, 260 and 250 nmol/min, respectively, for up to 30 minutes) into a
      veingraft anastomosed to a coronary vessel, and the coronary blood flow was
      measured. Plasma levels of endothelin from the coronary sinus and the periphery
      were determined. RESULTS: There were no significant changes in flow caused by
      endothelinA blockade alone or in combination with endothelinB blockade. There
      were no immediately increased levels of endothelin after surgery or after
      infusions of the endothelin blockers. CONCLUSIONS: Endothelin blockade does not
      influence the immediate perioperative myocardial blood flow after coronary bypass
      grafting. There is no significantly increased myocardial outflow of endothelin,
      and endothelin does not have any influence on the basal tone of the coronary
      vessels in the early phase after coronary bypass grafting.

PMID- 12238832
TI  - Tranexamic acid reduces bleeding and the need for blood transfusion in primary
      myocardial revascularization.
AB  - BACKGROUND: The objective of this study was to study the effect of low-dose
      tranexamic acid (TA) on postoperative bleeding and coagulation variables after
      coronary artery bypass grafting operation. METHODS: Fifty patients undergoing
      primary coronary artery bypass grafting were randomly assigned to receive either
      placebo (0.9% NaCl; n = 25) or 10 mg/kg TA followed by infusion of 1 mg/kg per
      hour during the operation (n = 25). Data measured included blood loss,
      transfusion, reoperation, fibrinogen level, fibrinogen split products, platelet
      size, and platelet function. Measurements were made after induction of
      anesthesia, after heparin administration, during patient warming, after skin
      closure, and 24 hours after operation. RESULTS: Patients in the TA study group
      weighed less. Other demographic characteristics were similar between groups.
      Postoperative bleeding was less in the TA group (194 +/- 135 mL versus 488 +/-
      238 mL, p < 0.001), whereas blood requirement was higher in the control group
      (1.68 +/- 1 versus 0.52 +/- 0.9 U of packed cells per patient, p < 0.001). The
      percent of patients exposed to blood products was significantly less in the TA
      group (36% versus 100%, p < 0.001). Fibrinogen split products were lower in the
      TA group during bypass (p < 0.001). Fibrinogen levels fell in both groups during
      cardiopulmonary bypass. Platelet number and function were reduced equally in both
      groups by cardiopulmonary bypass. Other test results were not different between
      groups. CONCLUSIONS: The use of low-dose TA during coronary artery bypass
      grafting significantly reduced the coagulopathy-induced postoperative bleeding
      and allogeneic blood products requirement. The low levels of fibrinogen split
      products during bypass in the study group reflect the inhibiting effect of TA in
      fibrinolysis. Tranexamic acid had no effect on platelet function during
      cardiopulmonary bypass.

PMID- 12238833
TI  - Validation of a bone analog model for studies of sternal closure.
AB  - BACKGROUND: The incidence of serious sternal wound complications may be reduced
      with improvements in closure methods. Biomechanical testing of median sternotomy
      closures in cadavers has proven useful but is limited by availability, high cost,
      and wide variations in the material properties of the sterna. This study tests
      whether artificial sterna can be used to replace whole cadavers in sternal
      closure testing. METHODS: Two common wire closure techniques were tested using
      both whole cadavers and artificial sternal models formed from bone analogue
      material. Sternal models were molded from polyurethane foam (20 lbs/ft3) to
      simulate the mechanical properties observed in human cadaveric sterna. The force
      vector previously identified as the most detrimental to sternal cohesion (lateral
      traction) was used to stress the closures. Separation of the incision site was
      measured at the manubrium, midsternum, and xiphoid and data were compared between
      cadaver and bench test groups. RESULTS: Sternal separations recorded in cadavers
      were found to be similar to bench test results for both closure types. Data
      variability within test groups was found to be consistently lower using
      artificial sterna, where peak standard deviations for sternal motion averaged
      less than half that measured in cadavers. CONCLUSIONS: Results suggest that
      anatomic sternal models formed from solid polyurethane foam can be used to
      approximate the biomechanical properties of cadaveric sterna and that reliable
      information regarding sternal closure stability can be secured through this
      means. Moreover, bench test data were shown to be less variable than cadaveric
      results, thus enhancing the power to detect small differences in sternal fixation
      stability.

PMID- 12238834
TI  - Ambulatory intraaortic balloon pump use as bridge to heart transplant.
AB  - BACKGROUND: This study evaluates a modification of an ambulatory intraaortic
      balloon pump (IABP) technique used in patients with heart failure of ischemic
      origin for bridge to transplant. METHODS: In this retrospective review we
      evaluated the ability to place the ambulatory IABP, any complications, time on
      device, and success in bridging to transplant on the ambulatory IABP device. In
      addition, the cost as compared to current ventricular assist devices was
      determined. RESULTS: Between July 2000 and November 2001, 4 patients have been
      managed with ambulatory IABP in our combined University of Wisconsin and William
      S. Middleton Veterans Administration programs. All 4 patients had ischemia as
      their mode of heart failure, and each had a relative contraindication to standard
      ventricular assist device use. All 4 patients had ambulatory IABPs successfully
      placed through the left axillary artery without complication, and were able to
      ambulate early after ambulatory IABP placement, and increased their
      rehabilitation status before transplantation. Ambulatory IABP support ranged from
      12 to 70 days. All 4 patients have been successfully transplanted and discharged
      from the hospital. Use of the ambulatory IABP support, even with multiple
      replacements, translated to 10- to 50-fold savings for each of the reported
      patients versus standard ventricular assist device use. CONCLUSIONS: As a result
      of our initial experience, we believe that ambulatory IABP is an excellent mode
      of support in selected patients, and is cost-effective, as compared to
      conventional ventricular assist device therapy.

PMID- 12238835
TI  - An ovine model of postinfarction dilated cardiomyopathy.
AB  - BACKGROUND: Coronary arterial disease is the major cause of congestive heart
      failure, but suitable animal models of postinfarction, dilated cardiomyopathy do
      not exist. This article describes an ovine model that develops after an
      anterobasal infarction. METHODS: The distribution of ovine myocardium supplied by
      the first two diagonal branches of the left homonymous artery were determined in
      20 slaughterhouse hearts and eight live sheep using methylene blue and
      tetrazolium injections, respectively. Seven additional animals had the infarction
      and underwent serial hemodynamic, microsphere and echocardiographic studies more
      than 8 weeks and histologic studies at the eighth week. Infarcts represented
      24.6% +/- 4.7% and 23.9% +/- 2.2% of the left ventricular mass in slaughterhouse
      and live hearts, respectively. RESULTS: During remodeling, left ventricular end
      systolic and end-diastolic volumes increased 115% and 73%, respectively, ejection
      fraction decreased from 41.2% +/- 6.7% to 29.1% +/- 5.7%, systolic wall
      thickening remote from the infarct decreased by 68%, sphericity index increased
      from 0.465 +/- 0.088 to 0.524 +/- 0.038, and left ventricular end-diastolic
      pressure increased from 1.7 +/- 1.0 to 8.2 +/- 3.5 mm Hg. Serial microsphere
      measurements documented normal blood flow (1.34 mL/g per minute) to all
      uninfarcted myocardium and 22% of normal to the infarct. Viable myocardium showed
      mild interstitial fibrosis. CONCLUSIONS: This ovine model meets all criteria for
      postinfarction, dilated cardiomyopathy and has the advantages of controlling for
      variations in coronary arterial anatomy, collateral vascularity, and differences
      in the numbers, location, and severity of atherosclerotic lesions that confound
      human studies of the pathogenesis of this disease. This simple model contains
      only infarcted and fully perfused, hypocontractile myocardium produced by a
      moderate-sized, regional infarction.

PMID- 12238836
TI  - Combined surgical and endovascular treatment of acute aortic dissection type A:
      preliminary results.
AB  - BACKGROUND: The established treatment modality of acute Stanford type A
      dissection includes repair of the ascending aorta and various portions of the
      aortic arch, whereas the descending aorta is left untreated. We report a
      simultaneous approach of open repair of the ascending aorta with transluminal
      stent grafting of the descending aorta to minimize the consequences of an
      untreated descending aorta. METHODS: From April 2001 to February 2002, 8
      consecutive patients (3 women [37.5%] and 5 men [62.5%]) with a mean age of 55.7
      years (range, 45 to 70 years) were intended to be treated with the combined
      method of surgical repair of the ascending aorta and transluminal stent grafting
      into the descending aorta during the period of deep hypothermic circulatory
      arrest. Circulatory arrest time ranged between 30 and 67 minutes (average, 38.8
      minutes). Specially designed Talent stent grafts (32 to 40 mm in diameter, length
      13 cm) were inserted under direct vision and deployed with the proximal end at
      the origin of the left subclavian artery. RESULTS: Intraoperative stent graft
      placement was successful in 7 patients (87.5%). Because of severe kinking of the
      distal arch, stent insertion failed in 1 patient (12.5%). One patient with a
      history of preoperative stroke in the middle cerebral artery died because of
      intracerebral bleeding on postoperative day 2, resulting in an in-hospital
      mortality of 12.5%. Mean intensive care unit stay was 6.4 days (range, 2 to 21
      days) and overall hospital stay was 18.2 days (range, 7 to 33 days). Completion
      computed tomographic scans revealed complete thrombosis of the false lumen in 2
      patients and partial thrombosis in 4 patients. Follow-up was complete and ranged
      from 1 to 9 months (mean, 5.4 months). CONCLUSIONS: This preliminary study shows
      that combined surgical and endovascular treatment of acute type A dissection is
      feasible, and at least partial thrombosis of the false lumen can be achieved,
      potentially minimizing the risk of further dilatation or rupture. Additionally,
      the stent graft expands the otherwise sickle-shaped true lumen, thereby
      ameliorating distal aortic perfusion. Long-term results are warranted to
      demonstrate the effectiveness of this new combined treatment modality.

PMID- 12238837
TI  - Overexpression of heat shock protein 60/10 in myocardium of patients with chronic
      atrial fibrillation.
AB  - BACKGROUND: Cardiomyocytes respond to chronic atrial fibrillation with increased
      expression of heat shock protein 60 (HSP60). The aim of this study was to
      investigate whether expression of the coprotein HSP10 is also increased. METHODS:
      Right atrial samples from 16 patients undergoing elective cardiac operation were
      excised and immediately frozen in liquid nitrogen. Eight patients had chronic
      atrial fibrillation and 8 patients were in sinus rhythm. The HSP60 and HSP10
      protein levels were determined by SDS-PAGE, Western blot, and quantified by
      optical densitometry according to the immunoreactive bands of actin. RESULTS: In
      myocardial samples from patients with chronic atrial fibrillation we found
      simultaneous upregulation of both stress proteins. HSP60 expression was more than
      2.3-fold and HSP10 expression was more than 2.4-fold increased in atrial
      myocardium of patients with chronic atrial fibrillation. CONCLUSIONS: These
      results indicate functional upregulation of mitochondrial HSP60 and HSP10 in
      response to chronic atrial fibrillation.

PMID- 12238838
TI  - Pericardial tissue valves and Gore-Tex conduits as an alternative for right
      ventricular outflow tract replacement in children.
AB  - BACKGROUND: There is still no perfect conduit for reconstruction of the right
      ventricular outflow tract (RVOT) in children. Homografts are not always available
      in the appropriate size, and degenerate in a few years. This study evaluates the
      pericardial valve with Gore-Tex conduit as an alternative for RVOT construction.
      METHODS: From January 1, 1993, to September 30, 1999, a pericardial tissue valve
      was inserted in all patients undergoing RVOT reconstruction or pulmonary valve
      replacement (PVR) who were large enough to accommodate a tissue valve. In
      patients without a native main pulmonary artery, a new technique was used to
      construct an RV-PA conduit out of a flat sheet of Gore-Tex, as Dacron frequently
      leads to stenosis. Data were collected by retrospective review, follow-up
      echocardiograms, and assessment by a single cardiologist. RESULTS: There were 48
      patients, 22 undergoing a PVR alone and 26 a RV-PA valved Gore-Tex conduit.
      Diagnosis included tetralogy of Fallot (n = 25); truncus arteriosis (n = 9);
      ventricular septal defect with PA (n = 5); DORV (n = 4); D-TGA with PS (n = 2);
      and 1 each IAA with sub AS, VSD with PI, and PS s/p Ross procedure. Patient age
      ranged from 3 to 33 years and 98% were reoperations. The valve sizes ranged from
      19 to 33 mm and the median hospital length of stay was 4 days. There were 2
      (4.2%) perioperative and 1 (2.1%) late deaths, none related to the valve or Gore
      Tex conduit. At a follow-up of 15 to 86 months (mean 43 +/- 16 months), all
      remaining 45 patients are New York Heart Association class I, all valves are
      functional, and no patient has required valve or conduit replacement or revision;
      more importantly, echocardiogram revealed no significant valve or conduit
      stenosis (mean gradient 16 +/- 8 mm Hg) and no evidence of regurgitation or
      structural degeneration. CONCLUSIONS: A pericardial tissue valve and Gore-Tex
      conduit provides a reliable alternative for RVOT reconstruction in pediatric
      patients. It is readily available, molds in the limited retrosternal space, and
      has outstanding intermediate results with no evidence of failure or deterioration
      up to 7 years after insertion.

PMID- 12238839
TI  - Fontan-type procedures: residual lesions and late interventions.
AB  - BACKGROUND: The purpose of this study was to determine the type and incidence of
      hemodynamic and electrophysiological abnormalities requiring surgical or catheter
      based interventions in a single-center long-term experience. METHODS: Eighty
      eight patients with a follow-up of at least 5 years (mean follow-up, 9.6 +/- 2.6
      years) after Fontan-type procedures were included. All patients had undergone
      cardiac catheterization either as part of the regular postoperative protocol or
      because of symptomatic atrial tachycardia or increasing cyanosis. RESULTS:
      Freedom from reoperation for up to 5 years was documented for 82% of patients and
      decreased to 76% after 8 years. Late reoperations included conversion of an
      atriopulmonary anastomosis to a total cavopulmonary anastomosis in 2 patients
      with atrial dysrhythmia and implantation of an extracardiac conduit in 1 patient
      with left atrial isomerism and intrapulmonary arteriovenous malformations after a
      Kawashima operation. Decline in sinus node function with symptomatic bradycardia
      required pacemaker therapy in 10 patients (11%). Transcatheter interventions
      included fenestration occlusion in 5 of the 11 patients with initial baffle
      fenestration. In 6 of 17 patients with aortopulmonary collaterals, coil occlusion
      was indicated to reduce future systemic ventricular volume load. Various systemic
      venous collaterals were documented in 11 patients and required coil occlusion in
      2. One patient with symptomatic protein-losing enteropathy underwent
      transcatheter fenestration creation without sustained relief of symptoms. Freedom
      from transcatheter interventions decreased from 94% to 82% after 5 and 10 years,
      respectively. CONCLUSIONS: During long-term follow-up, reoperations are rare and
      mainly involve Fontan conversion to either a lateral-tunnel or extracardiac
      conduit procedure. Detailed angiographic evaluation on a routine basis allows
      identification of the vascular sites of origin of aortopulmonary collateral
      vessels and systemic venous collaterals potentially developing during long-term
      follow-up. Transcatheter interventions including fenestration occlusion and
      occlusion of venous collaterals and aortopulmonary collaterals were performed to
      maintain and improve the Fontan circulation in clinically symptomatic and
      asymptomatic patients. During long-term follow-up after Fontan-type operations, a
      regular postoperative cardiac catheterization protocol is recommended.

PMID- 12238840
TI  - Management and outcome of patients with abnormal ventriculo-arterial connections
      and mitral valve cleft.
AB  - BACKGROUND: In patients with abnormal ventriculo-arterial connections, a mitral
      valve cleft different from an atrioventricular canal is occasionally associated.
      It may cause outflow obstruction, mitral regurgitation, and complicate
      biventricular repair. METHODS: A retrospective review identified 21 patients
      operated upon with mitral valve cleft, abnormal ventriculo-arterial connections,
      and two well-developed ventricles. Eight patients had a ventricular outflow
      obstruction due to the mitral valve, whereas 2 had more than mild mitral
      regurgitation. One patient required initial mitral valve surgery. Eleven patients
      underwent biventricular repair, associated with mitral valve repair in 2 cases:
      arterial switch operation (n = 4), Senning operation (n = 3) associated with an
      arterial switch operation in one case, intraventricular repair (n = 3), and
      Rastelli-type extracardiac conduit repair (n = 1). Single-ventricle palliation
      was preferred in 10 patients with major mitral valve straddling (n = 5), outflow
      tract obstruction (n = 2), and noncommitted or multiple VSDs (n = 3). RESULTS:
      There were three hospital deaths, two of which occurred after biventricular
      repair and one after an early reoperation after a bidirectional cavopulmonary
      anastomosis. Postoperatively after biventricular repair, 1 patient required
      permanent pacemaker implantation and 3 patients were reoperated on for subaortic
      stenosis (n = 1) and mitral regurgitation (n = 2), with one late death. By
      multivariate analysis, patients with a double-outlet right ventricle were at
      greater risk of death (p = 0.04). After a mean follow-up period of 60.7 months
      (+/- 68.6 months), 16 patients are in New York Heart Association (NYHA) class I.
      One patient with a moderate mitral regurgitation on Doppler study is in NYHA
      class II. CONCLUSIONS: The surgical management remains controversial in patients
      with abnormal ventriculo-arterial connections and mitral valve cleft.
      Biventricular repair may not always be feasible, especially in cases of complex
      intracardiac anatomy associated with mitral valve straddling. Single-ventricle
      palliation can be achieved in these patients, although it is unknown whether the
      long-term results are as good as those obtained with biventricular repair.

PMID- 12238841
TI  - Early postoperative arrhythmias after cardiac operation in children.
AB  - BACKGROUND: Arrhythmias are a recognized complication of cardiac operations.
      However, little is known about the incidence, treatment, and risk factors for
      early postoperative arrhythmias in children after cardiac operations. METHODS:
      Diagnosis and treatment of early postoperative arrhythmias were prospectively
      analyzed in an intensive care unit in 100 consecutive children with a median age
      of 17 months (range, 1 day to 191 months) who had undergone cardiac operation.
      Patients were grouped in three different categories of surgical complexity.
      RESULTS: During a median postoperative time of 1 day (range, 0 to 15 days), 64
      critical arrhythmias occurred in 48 patients. Arrhythmias consisted of sinus
      bradycardia in 30, atrioventricular block II to III in 7, supraventricular
      tachyarrhythmias in 14, and premature complexes in 13 instances. Treatment of 52
      arrhythmias was successful and included pacing in 41, intravenous amiodarone in
      8, body cooling in 5, overdrive pacing in 3, and electrolyte correction in 2
      cases, with more than one treatment modality in 8 cases. Risk factors for
      arrhythmias were lower body weight (p < 0.05), longer cardiopulmonary bypass
      duration (p < 0.05), and a category of higher surgical complexity (p < 0.001).
      CONCLUSIONS: Early postoperative arrhythmias occur frequently after cardiac
      operations in children. Sinus bradycardia, atrioventricular block II to III, and
      supraventricular tachyarrhythmias are the most frequent arrhythmias, which,
      however, can be treated effectively by means of temporary pacing, cooling, and
      antiarrhythmic drug therapy. Lower body weight, longer cardiopulmonary bypass
      duration, and a higher surgical complexity are risk factors for early
      postoperative arrhythmias.

PMID- 12238842
TI  - Intraoperative radiofrequency ablation of the atrium: effectiveness for treatment
      of supraventricular tachycardia in congenital heart surgery.
AB  - BACKGROUND: Supraventricular tachycardia (SVT) is common in surgical patients
      with congenital heart disease. Ablation and maze operations have been shown to be
      effective in treating SVT, but these procedures can be complex and time-consuming
      because of variable anatomy and a thickened right atrium. To simplify and shorten
      these procedures, we used a long, flexible radiofrequency probe capable of
      producing long ablation lines quickly and effectively. We report the initial
      results with this procedure. METHODS: Six patients aged 6 weeks to 40 years with
      refractory SVT were referred for reoperation for repair of complex congenital
      heart disease (transposition of the great vessels, Ebstein's anomaly, single
      ventricle, tetralogy of fallot). Intraoperative radiofrequency ablation was
      performed in the right atrium for refractory SVT as an adjunct to surgical
      reconstruction (redo Fontan, right atrial reduction plasty, right ventricular
      outflow tract reconstruction, tricuspid repair). Lesions were made with a
      radiofrequency probe using temperatures of 70 degrees C for 60 seconds. Lesions
      were placed between the coronary sinus and the tricuspid valve, between the
      tricuspid valve and the inferior vena cava, between the atrial septal defect and
      the superior and inferior vena cava in patients with intraatrial reentry
      tachycardia/atrial flutter, and at the location of the accessory pathway in a
      patient with Wolff-Parkinson-White syndrome. The long, flexible probe has
      multiple independently controlled segments allowing ablation lesions that conform
      to the atrial morphology. RESULTS: An average of five intraoperative
      radiofrequency ablation lesions per patient were made. Average time for ablation
      was 14 minutes. With up to 25 months' follow-up, 5 patients are in sinus rhythm,
      and 1 is in a paced atrial rhythm. The patient with Wolff-Parkinson-White
      syndrome showed no preexcitation after operation. No complications resulting from
      intraoperative radiofrequency ablation were encountered. CONCLUSIONS:
      Intraoperative radiofrequency ablation in the atrium is a safe, effective, and
      expeditious procedure for control of SVT in patients undergoing reoperation for
      congenital heart disease with refractory SVT.

PMID- 12238843
TI  - The infant with single ventricle and excessive pulmonary blood flow: results of a
      strategy of pulmonary artery division and shunt.
AB  - BACKGROUND: The infant with a single ventricle and excessive pulmonary blood flow
      requires early protection of the pulmonary vascular bed to insure suitability for
      a subsequent Fontan procedure. The traditional approach, pulmonary artery
      banding, has had disappointing results. We have pursued an alternate strategy:
      division of the pulmonary artery, and placement of a systemic-to-pulmonary artery
      shunt. Potential sites of systemic outflow tract obstruction are simultaneously
      bypassed, by either a Damus-Kaye-Stansel, or modified Norwood procedure. METHODS:
      From January 1996 to June 2001, 22 infants were treated by this strategy.
      Patients with hypoplastic left heart syndrome were excluded. Median age was 18
      days (range 2 days to 6 months). In addition to pulmonary artery division and
      shunt, 3 of 22 patients underwent a Damus-Kaye-Stansel procedure, and 13 of 22
      patients underwent a modified Norwood procedure. RESULTS: There were no operative
      deaths, and one late death. Actuarial survival beyond 30 months was 90%. At
      follow-up catheterization in 22 patients, median transpulmonary gradient was 7
      mmHg (range 4 to 18), and median pulmonary vascular resistance 1.9 Wood units
      (range 0.9 to 3.3). Twenty-one patients have undergone a subsequent bidirectional
      superior cavopulmonary connection, and 6 a Fontan procedure, with no deaths. No
      patient developed subaortic stenosis, or aortic arch obstruction. Neoaortic
      insufficiency was none or trivial in 12 patients, mild in 3, and moderate in 1.
      CONCLUSIONS: In patients with a functional single ventricle and excessive
      pulmonary flow, a strategy of pulmonary artery division and shunt, along with
      prophylactic bypass of systemic outflow obstruction, carries low operative and
      midterm mortality. It provides consistent protection of the pulmonary vascular
      bed, avoids subaortic stenosis and aortic arch obstruction, minimizes neoaortic
      insufficiency, and ensures suitability for progression along a Fontan pathway.
      These results provide a comparison for alternate strategies, including pulmonary
      artery banding.

PMID- 12238844
TI  - Do vitamins C and E attenuate the effects of reactive oxygen species during
      pulmonary reperfusion and thereby prevent injury?
AB  - BACKGROUND: We established an in vivo pig model of standardized lung ischemia to
      analyze pulmonary reperfusion injury. Enhanced chemiluminescence measurement (CM)
      allowed immediate quantification of reactive oxygen species (ROS) and subsequent
      lipid peroxidation. In such model we analyzed efficacy of vitamins C and E to
      prevent reperfusion injury. METHODS: After left lateral thoracotomy in group I (n
      = 6), normothermic lung ischemia was maintained for 90 minutes followed by a 5
      hour reperfusion period. In group II, animals (n = 6) underwent ischemia as in
      group I, but received vitamins (preoperative IV bolus C = 1 g, E = 0.75 g, then
      continuous infusion (125 mg/h) each throughout the study). In Group III, animals
      (n = 6) underwent sham surgery and served as controls. Hemodynamic variables and
      gas exchange were assessed. The CM was performed for injury quantification in
      blood samples and to determine activation of isolated PMNs. The Wilcox rank test
      was used for statistical analysis. RESULTS: During reperfusion, all animals in
      group I developed significant pulmonary edema with significant loss of pulmonary
      function. The addition of vitamins (group II) improved oxygenation and almost
      abolished pulmonary inflammatory cell infiltration; however, as in group I,
      pulmonary compliance still tended to decline and the number of circulating
      leucocytes increased. The CM showed that, compared with group I, vitamins reduced
      O2- basic release by PMNs significantly (460% to 170%, p < 0.05; control 165%),
      but could not prevent an increase of free ROS in whole blood similar to group I
      (443% to 270%, p = ns, control 207%). With regard to lipid peroxidation only a
      trend of reduction was observed (117% to 105%, p = ns, control 100%).
      CONCLUSIONS: Differentiated analysis by CM demonstrated that vitamins C and E
      inhibited PMN activation but were not able to prevent radical production by other
      sources. This offers a potential explanation why radical scavengers like vitamins
      only attenuate but ultimately do not prevent reperfusion injury.

PMID- 12238845
TI  - Clinical performance and biocompatibility of poly(2-methoxyethylacrylate)-coated
      extracorporeal circuits.
AB  - BACKGROUND: Poly(2-methoxyethylacrylate) is an amphiphilic organic polymer
      consisting of a hydrophobic backbone with pendant hydrophilic groups that has
      been reported to reduce protein and platelet adsorption in in vitro and ex vivo
      studies. METHODS: Sixty patients undergoing three-vessel coronary artery bypass
      grafting were divided into two equal groups. Group 1 had operation with Capiox
      poly(2-methoxyethylacrylate) coated SX18R oxygenators with noncoated circuits,
      and group 2 had operation with all noncoated circuits. Hemodynamic variables,
      blood and urine test results, hematologic variables, complement fractions, C3a
      and C4d, and interleukin-6 levels were documented preoperatively (T1), on
      cardiopulmonary bypass (T2), before cessation of cardiopulmonary bypass (T3),
      after protamine sulfate reversal (T4), and on the first postoperative day (T5).
      Protein electrophoresis was performed at T1 and T5. Blood cell adhesion and
      aggregation on fibers were analyzed with optical microscopy, and desorbed protein
      was evaluated quantitatively by a spectrophotometer using samples obtained when
      the oxygenators were dismantled after cardiopulmonary bypass. RESULTS: Platelet
      counts in group 1 demonstrated significant differences at T3, T4, and T5 (p <
      0.05) versus group 2 and white blood cell counts in group 1 versus group 2, at
      counts T4 and T5. Albumin levels were significantly better preserved in group 1
      at T4, and T5 and fibrinogen levels, at T3 and T5 (p < 0.05). On electrophoresis,
      the postoperative albumin level was 57.9% +/- 3% in group 1 versus 50.2% +/- 3%
      in group 2 (p < 0.05). Postoperative hemorrhage was 452 +/- 35 mL in group 1 and
      612 +/- 35 mL in group 2 (p < 0.05). Duration of intubation was significantly
      lower (p < 0.05) in group 1, as was need of blood transfusion (p < 0.01). More
      platelet adhesion and aggregation were demonstrated on noncoated oxygenator
      fibers. The amount of desorbed protein was 0.13 +/- 0.01 mg/dL versus 0.012 +/-
      0.001 mg/dL (p < 0.001) on noncoated versus coated fibers, respectively.
      CONCLUSIONS: Poly(2-methoxyethylacrylate)-coated oxygenators reduce platelet
      adhesion, platelet aggregation and protein adsorption. This surface provides a
      better perioperative clinical status through platelet-, albumin-, and fibrinogen
      sparing effects.

PMID- 12238846
TI  - Reduction in brain embolization using the Aegis aortic cannula during bypass in
      swine.
AB  - BACKGROUND: Cerebral embolization during cardiopulmonary bypass (CPB) is an
      important cause of neurologic injury. This study determined whether a new aortic
      cannula (Cardeon Aegis) could substantially reduce brain embolization in a swine
      CPB model. METHODS: Fourteen 70-kg pigs underwent normothermic CPB, 7 animals
      with the Aegis device and 7 with a control cannula. Cerebral blood flow was
      determined using 15-microm fluorescent microspheres before bypass and twice
      during CPB. After the second bypass CBF measurement, animals were embolized with
      120,000 78-microm fluorescent microspheres at normothermia. At the end of the
      experiment the brain, eyes, kidneys, myocardium, and small bowel were removed and
      the microspheres isolated. RESULTS: Cerebral blood flow was equivalent between
      groups before bypass and during both bypass periods. While the two groups were
      equivalent with regard to pump flow, temperature, hemoglobin, and PaCO2, use of
      the Aegis cannula markedly reduced embolization to three of four brain regions.
      Deployment of the baffle reduced total brain embolization by 91% from a mean of
      22 +/- 21 emboli per gram in the control animals to 2 +/- 6 emboli per gram in
      animals receiving the Aegis device. CONCLUSIONS: Cerebral blood flow with the
      Aegis device is equal to or greater than that observed under nonbypass conditions
      and that seen with conventional aortic cannulas. However, cerebral embolization
      is profoundly reduced by use of the Aegis device. The application of this cannula
      may reduce postcardiac surgical neurologic injury.

PMID- 12238847
TI  - Glucocorticoids reduce ischemia-reperfusion-induced myocardial apoptosis in
      immature hearts.
AB  - BACKGROUND: Transient myocardial dysfunction often occurs after ischemia
      reperfusion with immature myocardium appearing particularly susceptible.
      Neutrophil adhesion and activation contribute to ischemia-reperfusion injury
      after cardiopulmonary bypass (CPB), possibly resulting in cell death. The
      hypothesis was that glucocorticoids could prevent reperfusion-induced myocardial
      dysfunction by blunting leukocyte-mediated injury. METHODS: Neonatal piglets were
      cooled with CPB followed by 2 hours of circulatory arrest. Animals were rewarmed,
      removed from CPB, and allowed to recover for 2 hours. Methylprednisolone (60
      mg/kg) was administered in the CPB priming solution to one group (intraoperative
      glucocorticoids). In another group (preoperative glucocorticoids), 30 mg/kg
      methylprednisolone was administered 6 hours before CPB in addition to the
      intraoperative dose (30 mg/kg). Control animals received no glucocorticoids.
      RESULTS: Apoptotic myocardial cells measured by terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick-end labeling assay and
      caspase-3 activity were reduced in animals administered glucocorticoids compared
      with controls (p < 0.05). Animals receiving either intraoperative or preoperative
      glucocorticoids had 0.10 +/- 0.07 and 0.13 +/- 0.05 apoptotic cells per high
      power field, respectively, whereas 0.33 +/- 0.15 apoptotic cells were detected
      with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate
      nick-end labeling in control animals. Glucocorticoid administration reduced
      myocardial intercellular adhesion molecule-1 and monocyte chemoattractant protein
      1 mRNA expression compared with control piglets. Maximum rate of increase of left
      ventricular pressure was 62% +/- 9% of baseline in control animals at 120 minutes
      of recovery compared with 96% +/- 6% and 95% +/- 10% of baseline in animals
      receiving intraoperative and preoperative glucocorticoids, respectively (p <
      0.05). CONCLUSIONS: The reduction of neutrophil adhesion and activation proteins
      in neonatal myocardium was associated with less apoptotic cell death after
      glucocorticoid administration. The blunting of apoptosis in glucocorticoid
      treated animals was also associated with improved recovery of left ventricular
      systolic function in neonatal animals after CPB and circulatory arrest.
      Glucocorticoid attenuation of myocardial apoptosis might have important
      implications for maintaining long-term ventricular function after ischemia and
      reperfusion.

PMID- 12238848
TI  - Pharmacological preconditioning ameliorates neurological injury in a model of
      spinal cord ischemia.
AB  - BACKGROUND: Pharmacological openers of mitochondrial ATP-sensitive potassium
      (mitoKATP) channels have been shown to mimic ischemic preconditioning (IPC) in
      both the brain and myocardium. We hypothesized that similar endogenous mechanisms
      exist in the spinal cord and that diazoxide, a potent mitoKATP opener, could
      reduce neurologic injury after aortic cross-clamping in a model of spinal cord
      ischemia. METHODS: The infra-renal aorta was cross-clamped in 45 male New Zealand
      white rabbits for 20 minutes. Control animals received no pretreatment. Diazoxide
      treated animals were dosed (5 mg/kg) 15 minutes before cross-clamp. A third group
      underwent 5 minutes of IPC 30 minutes before cross-clamp. Two groups received
      KATP antagonists, 5-hydroxydecanoic acid (5-HD, 20 mg/kg) or glibenclamide (1.0
      mg/kg), before diazoxide administration. Systemic hypotension was induced in a
      final group with excess isoflurane. Tarlov Scoring was used to assess neurologic
      function at 24 and 48 hours, after which, the spinal cords were procured for
      histopathological analysis. RESULTS: Tarlov scoring demonstrated marked
      improvement in the Diazoxide group compared with control at 24 hours (p < 0.02)
      and 48 hours (p < 0.009). Moreover, no further neurologic injury occurred in this
      group at 7 days. IPC-treated animals showed neurologic improvement but were not
      significantly different from controls. Further, administration of glibenclamide
      was effective in antagonizing diazoxide's protective effect. CONCLUSIONS:
      Administration of diazoxide resulted in significant improvement in neurologic
      outcome in this model. This protective effect improved outcome at both early and
      late time points. Further, the antagonistic effect of glibenclamide implicates
      diazoxide's ATP-dependent potassium channel agonism as the mechanism of
      protection. Overall, this study suggests that diazoxide may be useful in the
      prevention of neurologic injury after thoracic aneurysm surgery.

PMID- 12238849
TI  - Adenosine A2A agonist reduces paralysis after spinal cord ischemia: correlation
      with A2A receptor expression on motor neurons.
AB  - BACKGROUND: The adenosine A2A agonist ATL-146e ameliorates reperfusion
      inflammation, reducing subsequent paralysis and neuronal apoptosis after spinal
      cord ischemia. We hypothesized that neuroprotection with ATL-146e involves
      inducible neuronal adenosine A2A receptors (A2A-R) that are upregulated after
      ischemia. METHODS: Eighteen rabbits underwent laparotomy, and 14 sustained spinal
      cord ischemia from cross-clamping the infrarenal aorta for 45 minutes. One group
      (ischemia-reperfusion [I/R] + ATL) received ATL-146e intravenously for 3 hours
      during spinal cord reperfusion. A second group (I/R) received equivolume
      intravenous saline solution for 3 hours and served as an ischemic control, and a
      third group (Sham) underwent sham laparotomy. At 48 hours, all subjects were
      assessed for motor impairment using the Tarlov scoring system (0 to 5). Lumbar
      spinal cord sections were immunolabeled for A2A-R and graded in a blinded fashion
      using light microscopy. RESULTS: There was a significant improvement in Tarlov
      scores in I/R + ATL animals compared with the I/R group. Sham-operated animals
      demonstrated no A2A-R immunoreactivity. There was a dramatic increase in A2A-R
      immunoreactivity in neurons of lumbar spinal cord sections from I/R compared with
      I/R + ATL and sham-operated animals. CONCLUSIONS: Reduction in paralysis in
      animals receiving ATL-146e correlates with the new finding of A2A-R expression on
      lumbar spinal cord motor neurons after ischemia. Adenosine A2A agonists may exert
      neuroprotective effects by binding to inducible neuronal A2A-R that are
      upregulated during spinal cord reperfusion, and reduced in response to
      administration of an A2A-R-specific agonist.

PMID- 12238850
TI  - Sleeve lobectomy for bronchogenic cancers: factors affecting survival.
AB  - BACKGROUND: Sleeve lobectomy is a parenchyma-sparing procedure that is
      particularly valuable in patients with cardiac or pulmonary contraindications to
      pneumonectomy. The purpose of this study is to report our experience with sleeve
      lobectomy for bronchogenic cancer and to investigate factors associated with long
      term survival. METHODS: Between January 1981 and June 2001, 169 patients
      underwent sleeve lobectomy for non-small-cell lung cancer (n = 139) or carcinoid
      tumor (n = 30), including 61 with a preoperative contraindication to
      pneumonectomy. Mean age was 59 +/- 14 years (range, 19 to 82 years). Vascular
      sleeve resection was performed in 11 patients. The remaining bronchial stump
      contained microscopic disease in 7 patients. RESULTS: Major bronchial anastomotic
      complications occurred in 6 (3.6%) patients: one was fatal postoperatively, three
      required reoperation, and two were managed conservatively. In the non-small-cell
      lung cancer group, operative mortality was 2.9% (4 of 139), and overall 5-year
      and 10-year survival rates were 52% and 28%, respectively. Six patients
      experienced local recurrence after complete resection. By multivariate analysis,
      two factors significantly and independently influenced survival: nodal status (N0
      or N1 versus N2; p = 0.01) and microscopic invasion of the bronchial stump (p =
      0.02). In the carcinoid tumor group, there were no operative deaths, and overall
      5-year and 10-year survival rates were 100% and 92%, respectively. CONCLUSIONS:
      Sleeve lobectomy achieves local tumor control and is associated with low
      mortality and bronchial anastomotic complication rates. Long-term survival is
      excellent for carcinoid tumors. For patients with non-small-cell lung cancer, N2
      disease or incomplete resection is associated with a worse prognosis; outcome is
      not affected by presence of a preoperative contraindication to pneumonectomy.

PMID- 12238851
TI  - Thoracoscopic lobectomy: a safe and effective strategy for patients with stage I
      lung cancer.
AB  - BACKGROUND: Thoracoscopic lobectomy is emerging as a potential alternative to
      thoracotomy for early stage lung cancer. The issues of safety and oncologic
      efficacy should be analyzed before recommending this procedure for widespread
      use. METHODS: Thoracoscopic lobectomy was attempted in 110 consecutive patients
      (age, 35 to 81 years) with tumors that were judged to be amenable to lobectomy
      over a 26-month period. Exclusion criteria included tumors greater than 5 cm in
      diameter, T3 tumors, endobronchial tumors visible at bronchoscopy, the use of
      induction therapy, extensive N1 disease on computed tomographic scan, and N2
      disease at mediastinoscopy. The procedures were performed without rib spreading
      using two ports and included anatomic hilar dissection and individual vessel
      stapling. RESULTS: Thoracoscopic lobectomy and mediastinal lymph dissection was
      successfully performed in 108 patients (98.2%); 2 patients required conversion to
      thoracotomy to control bleeding in the setting of dense hilar adenopathy. There
      were no intraoperative deaths and 4 perioperative deaths (3.6%) caused by
      pneumonia and associated adult respiratory distress syndrome (3 patients) and
      stroke (1 patient). Major complications included pneumonia (5 patients), stroke
      (1 patient), and return to the operating room to revise the bronchial closure (1
      patient). Minor complications included prolonged air leak (6 patients), atrial
      fibrillation (4 patients), blood transfusion (2 patients) and ileus (1 patient).
      Median time to chest tube removal was 3 days, and median length of stay was 3
      days. CONCLUSIONS: Thoracoscopic lobectomy is a safe and effective strategy for
      patients with early stage lung cancer. Long-term follow-up is required to
      determine if recurrence rate and 5-year survival are comparable with thoracotomy
      for lobectomy.

PMID- 12238852
TI  - Lobe-sparing resection of multiple pulmonary metastases with a new 1318-nm Nd:YAG
      laser--first 100 patients.
AB  - BACKGROUND: A new 1318-nm Nd:YAG laser has been developed to utilize the second
      wavelength (1318 nm; 40 watt) to more precisely cut, coagulate, and seal lung
      tissue adjacent to pulmonary nodules. This laser allows a precise
      intraparenchymal nodulectomy with a 5-mm rim of tissue destruction and subsequent
      lung parenchymal reapproximation to avoid lobar distortion. Resection of
      multiple, bilateral, and recurrent tumors in the lung is facilitated by this
      laser technique. METHODS: In 100 consecutive patients (53 men, mean age 60 years;
      47 women, mean age 61 years) with various primaries (most commonly renal and
      colorectal), 155 laser resections were performed via anterolateral thoracotomy
      (staged 3 to 4 weeks, if bilateral) using a new 1318-nm Nd:YAG laser. All
      palpable and visible masses were removed with 2 to 3-mm visible tumor margins
      (plus a 5-mm rim of residual lung necrosis secondary to laser energy dispersal)
      if the tumor or residual lung ratio was judged favorable. No stapling devices or
      bioadhesives were used. RESULTS: Six hundred thirty-two metastases (6.3 per
      patient, range 1 to 124) were resected. Despite 41% centrally located metastases,
      tumor resections were possible in 95% of patients with only a 5% lobectomy rate.
      Of the 100 patients, 67 were considered "curative" with complete metastasectomy
      by inspection and palpation, and 23 were judged incomplete from too extensive
      tumor or residual lung, miliary lung spread, or pleural studding. There were no
      associated mortalities and two complications, including bleeding (1) and a
      prolonged airleak (1), both treated conservatively. Follow-up was complete in all
      patients for a median of 26.5 months with clinic visits and chest computed
      tomographic scan every 3 to 6 months. Nine recurrences were detected and
      underwent reoperation. Overall survival in the completely resected "curative"
      group was 85% at 1 year, 71% at 2 years, 69% at 3 years, 57% at 4 years, and 32%
      at 5 years; in the completely resected "palliative" group, they were 70% at 1
      year, 36% at 2 years, 12% at 3 years, and 0 at 4 years; in the incomplete group,
      they were 56% at 1 year, 30% at 2 years, and 0 at 3 years. CONCLUSIONS: The new
      1318-nm Nd:YAG laser is parenchyma-sparing, improves complete resection rates,
      and potentially improves survival with fewer required lobectomies.

PMID- 12238853
TI  - Sentinel nodal assessment in patients with carcinoma of the lung.
AB  - BACKGROUND: Assessment of sentinel nodes to predict metastases in a regional
      nodal basin is valuable for staging patients with melanoma and breast carcinoma.
      This study tested whether injection of isosulfan blue and technetium-99 could
      identify mediastinal sentinel nodes in patients with lung carcinoma and determine
      whether sentinel node histology predicts distal nodal metastases. METHODS:
      Isosulfan blue and technetium-99 were injected into the tumor and pulmonary
      resection performed. The hilum and mediastinum were assessed visually and with
      the gamma probe, and a mediastinal nodal dissection was performed. RESULTS:
      Thirty-one patients were evaluated. Three patients had positive sentinel nodes
      and positive distal mediastinal nodes. Twenty-two patients had negative sentinel
      nodes and negative distal nodes. No sentinel node was identified in 6 patients
      and 2 patients had two sentinel nodes. CONCLUSIONS: These data demonstrate that
      this rapid, simple technique can identify sentinel nodes in the mediastinum and
      that the sentinel node is an accurate predictor of distal nodal metastases in
      patients with lung cancer.

PMID- 12238854
TI  - Completion pneumonectomy: factors affecting operative mortality and
      cardiopulmonary morbidity.
AB  - BACKGROUND: The purpose of this report is to analyze preoperative and
      perioperative factors affecting operative mortality and cardiopulmonary morbidity
      after a completion pneumonectomy. METHODS: We retrospectively reviewed all
      patients who underwent completion pneumonectomy from January 1985 through
      September 1998 at the Mayo Clinic in Rochester, MN. Factors affecting operative
      mortality and postoperative morbidity and were analyzed using univariate and
      multivariate analysis. RESULTS: There were 115 patients (73 men and 42 women),
      with a median age of 64 years (range, 12 to 83 years). Indication for
      pneumonectomy was benign disease in 57 patients (49.6%), lung cancer in 51
      (44.3%) and metastatic disease in 7 (6.1%). There were 24 deaths (mortality
      20.9%, 95% CI 13.9% to 29.4%). Mortality for patients undergoing completion
      pneumonectomy for benign disease, lung cancer, and metastatic cancer was 26.3%,
      17.6%, and 0%, respectively (p = 0.24). Factors adversely affecting mortality
      with univariate analysis included advanced age (p = 0.004), preoperative
      corticosteriod use (p = 0.01), decreased preoperative diffusion capacity of lung
      to carbon monoxide (p = 0.01), intraoperative blood transfusion (p = 0.04), and
      excessive crystalloid infusion within the first 12 hours (p = 0.01) and 24 hours
      (0.03) postoperatively, respectively. Factors adversely affecting mortality with
      multivariate analysis included advanced age (p = 0.001), preoperative
      corticosteriod use (p = 0.002), and low preoperative hemoglobin (p = 0.02).
      Cardiopulmonary complications occurred in 72 patients (63.7%). Factors adversely
      affecting morbidity with univariate analysis included benign disease (p = 0.002),
      decreased preoperative diffusion capacity of lung to carbon monoxide (p = 0.04),
      bronchial stump reinforcement (p = 0.0001), and excessive crystalloid infusion
      within the first 12 hours (p = 0.006) and 24 hours (p = 0.02) postoperatively,
      respectively. Factors adversely affecting morbidity with multivariate analysis
      included advanced age (p = 0.005) and bronchial stump reinforcement (p = 0.001).
      CONCLUSIONS: Multiple factors adversely affect operative mortality and
      cardiopulmonary morbidity after completion pneumonectomy. Although completion
      pneumonectomy remains a high-risk procedure, especially for benign disease, it
      still should be considered a treatment option in selected patients.

PMID- 12238855
TI  - Thoracoscopic sympathectomy for symptomatic arterial obstruction of the upper
      extremities.
AB  - BACKGROUND: Severely symptomatic arterial insufficiency of the hand and upper
      extremities requires adequate treatment. Medical therapy and local care are
      usually unsuccessful, and thoracic sympathectomy can represent an effective
      procedure to control pain, to help ulcer healing, and to prevent or delay
      amputation. METHODS: We performed 20 thoracoscopic sympathectomies in 15 patients
      (13 men and 2 women) with upper extremity ischemia. Mean age was 47 years (range
      21 to 72 years). All patients were thought to have organic blockage of digital
      arteries. The condition was unilateral in 10 patients and bilateral in 5. Primary
      diagnosis was digital arteriosclerosis in 8 patients, Buerger's disease in 4
      patients and the remaining 3 were drug abusers with severe ischemia due to
      accidental intraarterial injection of drugs. Eleven patients (73%) presented with
      terminal digital necrosis, gangrene, or ulceration of the fingers associated with
      severe pain. Four patients complained of coldness, pain, and some degree of soft
      tissue infection without permanent loss of tissue. RESULTS: We performed 10
      unilateral and five bilateral staged (mean interval was 3 months) thoracoscopic
      sympathectomies. We had two minor complications and no mortality. Mean duration
      of postoperative chest drainage was 2.5 +/- 0.4 days and mean postoperative
      hospital stay was 5.3 +/- 0.5 days. Follow-up ranged from 3 to 71 months, with a
      mean of 33 months. All patients demonstrated clinical benefit after operation.
      CONCLUSIONS: Thoracoscopic sympathectomy in patients with severe ischemia of
      upper limb extremities permits optimal symptomatic control and maximum tissue
      salvage. Because the procedure is minimally invasive, safe, and associated with a
      low rate of complications, it should be considered earlier the natural course of
      this disease.

PMID- 12238856
TI  - Ruptured hydatid cysts of the lung in children: clinical review and results of
      surgery.
AB  - BACKGROUND: Rupture of a hydatid cyst may cause some unique problems, especially
      in children. METHODS: Sixty-three children with a total of 68 ruptured lung
      hydatid cysts were operated on between 1980 and 2000. Mean age was 12.3 years
      (range, 1 to 15 years). Radiographic findings were hydropneumothorax (20.6%) and
      air-fluid level (19%). Mean follow-up was 19.3 months. RESULTS: Transthoracic
      needle aspiration was responsible for the rupture in 3 children. The interval
      between cyst rupture and operation was less than 24 hours in 10 patients (15.9%),
      1 to 4 days in 36 (57.1%), and more than 4 days in 17 (27%). Resection rate was
      22.1%. The most frequent operative method was cystotomy and capitonnage (38%).
      Morbidity was 25.4% (extended air leak 5, empyema 3, bronchopleural fistula 3,
      atelectasis 3, pneumonia 2). Mortality was 4.7% (hemoptysis 1, pneumonia and
      sepsis 1, aspiration of hydatid material 1). Morbidity and mortality seem to be
      more frequent in late cases. CONCLUSIONS: Early surgical intervention with single
      lung ventilation and maximum parenchyma preservation are recommended.

PMID- 12238857
TI  - Single-pass isolated lung perfusion versus recirculating isolated lung perfusion
      with melphalan in a rat model.
AB  - BACKGROUND: Isolated lung perfusion (ILuP) with melphalan (MN) is superior to
      intravenous infusion for the treatment of pulmonary carcinoma and sarcoma
      metastases. However, it is unknown whether a bolus injection of MN into the
      perfusion circuit or ILuP with a fixed concentration of MN will result in the
      highest lung levels. METHODS: ILuP with 0.5 mg MN was performed in Wag-Rij rats
      for 30 minutes either by a single-pass system (SP) (fixed concentration) (n = 10)
      or by reperfusion (RP) (bolus injection) (n = 10). In a separate experiment, rats
      were perfused with blood as the perfusate. In a third experiment, tumor levels
      were compared between SP, RP, or intravenous therapy with a dose of 0.5 mg. For
      induction of pulmonary metastases, 0.5 x 10(6) single adenocarcinoma cells were
      injected intravenously and therapy was given on day 30. For comparison of drug
      concentrations, unpaired Student's t test was applied. Statistical significance
      was accepted at p less than 0.05. RESULTS: Lung perfusion studies were
      succesfully performed without systemic leakage. Temperature of perfusate and rats
      was 34 degrees C to 37 degrees C. A significantly higher hematocrit (mean 27.9)
      compared with buffered starch (mean 2.5) did not result in higher MN lung levels
      or lower wet-to-dry ratio. Tumor levels were significantly higher after ILuP
      compared with intravenous therapy. However, no difference in tumor and lung
      levels was seen between single-pass and reperfusion. CONCLUSIONS: Both ILuP
      techniques resulted in significantly higher MN lung levels than after intravenous
      therapy. Because no difference was seen between single-pass and recirculating
      perfusion, MN can be injected as a bolus into the closed perfusion circuit.

PMID- 12238858
TI  - Regulation of chemokine expression by cyclosporine A in alveolar macrophages
      exposed to hypoxia and reoxygenation.
AB  - BACKGROUND: We have recently demonstrated a role for selected chemokines in a rat
      model of lung ischemia reperfusion injury (LIRI). We have further shown that
      pretreatment with cyclosporine A (CSA) is protective. The precise cellular events
      regulating this model are unknown. The alveolar macrophage (AM) is a key effector
      cell in multiple models of acute lung injury, and it likely plays a central role
      in LIRI as well. The present studies were undertaken to determine whether CSA
      functions in part by modifying the chemokine response of AMs to hypoxia and
      reoxygenation in vitro. METHODS: Alveola macrophages were rendered hypoxic (0.5%)
      for 2 hours and reoxygenated for 6 hours. The secreted chemokine content in the
      media was quantified by enzyme-linked immunosorbent assay, and nuclear protein
      was analyzed after electro-mobility shift assay. When employed, CSA was
      administered 30 minutes before hypoxia. RESULTS: Alveolar macrophages
      demonstrated a marked increase in the secretion of the chemokines, MIP-2, MIP
      1alpha, CINC, and MCP-1, in response to hypoxia and reoxygenation. This increase
      was dependent on mRNA transcription and de novo protein synthesis. It was also
      blocked by a specific inhibitor of the nuclear translocation factor, NF-kappaB.
      Pretreatment with CSA (500 ng/mL) significantly reduced expression of chemokines
      and activation of NF-kappaB. CONCLUSIONS: Cyclosporine A attenuates the chemokine
      response of AMs in vitro to hypoxia and reoxygenation at the pretranscriptional
      level through modulation of NF-kappaB. These findings suggest the potential
      mechanism of action of CSA's protective effects in lung ischemia reperfusion
      injury.

PMID- 12238859
TI  - Repair of damaged internal mammary artery.
AB  - The use of the internal mammary artery (IMA) in coronary artery bypass graft
      surgery is an independent predictor of late survival in all subsets of patients
      and should not be denied to any subgroup. Therefore damage to the IMA during
      harvesting is a catastrophic complication after which the graft is usually
      discarded. We present here a simple and safe technique for repair of a damaged
      left IMA that allowed its rescue for grafting to the left anterior descending
      artery.

PMID- 12238860
TI  - Valve-sparing operation for aortic root aneurysm in patients with bicuspid aortic
      valve.
AB  - Aortic root aneurysms are not rare in patients with bicuspid aortic valve, but
      valve-sparing operations to treat them remain challenging. We describe our
      surgical method of reconstructing only two commissures, which is extremely simple
      and easy to reproduce without aortic stenosis.

PMID- 12238861
TI  - Successful treatment in a patient with Takayasu's arteritis and Marfan syndrome.
AB  - We report an unusual case of concomitant Takayasu's arteritis and Marfan syndrome
      manifesting left main coronary ostial obstruction and annuloaortic ectasia.
      Simultaneous surgical treatment consisting of left coronary ostium
      endarterectomy, coronary artery bypass grafting, and Bentall operation was
      performed. This case is unique in that the cardiovascular manifestations of
      Takayasu's arteritis and Marfan syndrome were both simultaneously presented and
      surgically treated.

PMID- 12238862
TI  - Recombinant factor VIIa after aortic valve replacement in a patient with
      osteogenesis imperfecta.
AB  - A 26-year-old man with osteogenesis imperfecta and severe aortic regurgitation
      was scheduled for aortic valve replacement. As previously described by other
      authors the operation was difficult owing to the friability and weakness of the
      tissues. Mean blood losses of 153 mL per hour during the first 7 postoperative
      hours were observed. Despite normal coagulation indicators the bleeding did not
      stop and recombinant factor VIIa was applied at 40 microg/kg. Bleeding was
      successfully stopped after this single application.

PMID- 12238864
TI  - Surgical excision of a hemangioendothelioma of the left ventricle.
AB  - Primary intracardiac neoplasms are most commonly histologically benign with only
      30% exhibiting signs of malignancy. Metastatic tumors of the heart are 30 times
      more common than primary cardiac tumors. Patients with intracardiac masses may
      present with dyspnea on exertion, thromboembolic events, pericarditis,
      arrhythmias, or congestive heart failure. In many, however, the diagnosis is made
      upon discovering a murmur in an otherwise asymptomatic patient.
      Hemangioendotheliomas are very rare tumors of the heart characterized by
      capillary-sized vessels lined by rounded and often multilayered endothelial
      cells. Cardiac muscle cells are found compressed between proliferating vascular
      channels. We present a patient with this unusual cardiac tumor with no previous
      cardiac history and a new systolic murmur.

PMID- 12238863
TI  - Left ventricular assist device for right side assistance in patients with
      transposition.
AB  - Right (systemic) ventricular dysfunction is well described after Senning
      operations for transposition of the great arteries, and patients with
      congenitally corrected transposition of the great arteries. Transplantation
      remains the only definitive therapy for refractory heart failure, however
      patients may deteriorate clinically prior to the availability of a donor heart.
      This report details the implantation of a TCI Heartmate (Thoratec Corp.,
      Pleaston, CA) as a morphologic right ventricular assist device to bridge these
      patients to transplantation.

PMID- 12238865
TI  - Modified Starnes operation for neonatal Ebstein's anomaly.
AB  - We report the case of a severely symptomatic neonate with Ebstein's anomaly. A
      modified Starnes operation was performed, but insufficient drainage of venous
      blood returning through thebesian veins caused overdistention of the right
      ventricle and severe left ventricular dysfunction. Urgent reestablishment of
      right ventricular-right atrial communication successfully resolved these
      problems.

PMID- 12238866
TI  - Total cavopulmonary connection via a thoracotomy.
AB  - We report a patient who underwent a total cavopulmonary connection with an
      extracardiac conduit through a right thoracotomy. The thoracotomy approach was
      useful in circumventing possible hazardous complications at the sternal reentry
      for the completion of a staged Fontan due to previous mediastinitis in this
      patient.

PMID- 12238868
TI  - Salvage of right colon interposition by microsurgical venous anastomosis.
AB  - Venous insufficiency of a right colon interposition in esophageal reconstruction
      can be a fatal complication resulting in total failure. A case is presented of
      the salvage of the right colon interposition by additional microsurgical venous
      anastomosis to relieve the problem of venous stasis. The outcome was successful
      in a young patient with a complicated medical history.

PMID- 12238867
TI  - Anomalous origin of left coronary artery from the right pulmonary artery in
      association with type III aortopulmonary window and interrupted aortic arch.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery, also
      known as Garland-Bland-White syndrome, usually occurs as an isolated condition.
      We report an infant with caudal regression sequence diagnosed with interrupted
      aortic arch type B and type III aortopulmonary window, who was found to have
      anomalous origin of the left coronary artery from the right pulmonary artery at
      surgical repair. Successful repair of the aortopulmonary window and interruption
      was performed with reimplantation of the left coronary artery into the ascending
      aorta. This report highlights the importance of closely assessing the coronary
      ostia in patients undergoing complex aortopulmonary window repair.

PMID- 12238869
TI  - Simultaneous bronchopleural and esophagopleural fistulas after pneumonectomy.
AB  - The simultaneous occurrence of bronchopleural fistula (BPF) and esophagopleural
      fistula (EPF) after pneumonectomy is very rare. We describe a 60-year-old man who
      developed empyema associated with bronchopleural fistula as a complication of a
      right pneumonectomy. Initial chest tube drainage and antibiotic therapy were
      ineffective. Five months later ingested food particles appeared in the drainage
      fluid. Esophagoscopy revealed an esophageal fistula of 10 mm in diameter. After
      nutritional support by feeding jejunostomy both BPF and EPF were repaired by
      subscapular muscle myoplasty and extensive thoracoplasty through a right
      thoracotomy. Endoscopic examination performed 1 month after surgery showed
      complete closure of both fistulas and 9 months after surgery the patient was
      eating and gaining weight. The patient's death was due to aspiration pneumonia of
      another origin.

PMID- 12238870
TI  - Synchronous presentation of primary non-small cell lung carcinoma and
      pheochromocytoma.
AB  - A 54-year-old man was diagnosed with a 3.2-cm primary right lower lobe non-small
      cell lung cancer and a synchronously present 2.5-cm right adrenal gland mass.
      Workup of the adrenal lesion revealed a pheochromocytoma. The patient underwent
      combined mediastinoscopy, laparoscopic right adrenalectomy, and right thoracotomy
      with right lower lobectomy. This case illustrates the importance of establishing
      a firm diagnosis for all synchronously present adrenal lesions that are
      discovered in the setting of primary lung carcinoma.

PMID- 12238871
TI  - Scopulariopsis fungus ball.
AB  - We report on a 67-year-old woman with a rare Scopulariopsis fungus ball in the
      right middle lung lobe. Pathologic examinations after right middle lobectomy
      showed that the lesion contained a moniliaceous mold fungus that was cultured and
      identified as Scopulariopsis. The patient's postsurgery course was uneventful.

PMID- 12238872
TI  - Traumatic extrathoracic lung herniation.
AB  - Traumatic extrathoracic lung herniation is an exceptional complication of blunt
      chest trauma. We report the case of a 46-year-old man who was involved in a
      motorcycle accident and who suffered a left clavicle fracture-dislocation
      associated with multiple rib fractures and massive herniation of the left upper
      lobe through an upper anterior chest wall defect. Immediate surgical repair
      through an atypical transcostal vertical thoracotomy resulted in full recovery of
      pulmonary function at 1 year.

PMID- 12238873
TI  - Spontaneous rupture of the right hemidiaphragm after video-assisted lung volume
      reduction operation.
AB  - Lung volume reduction operation is an important therapeutic option in patients
      with advanced emphysema. We report a case of spontaneous rupture of the right
      diaphragm after a video-assisted thoracoscopic surgical procedure for emphysema.
      The pathophysiology of this complication is also discussed, along with practical
      points for perioperative management of emphysematous patients.

PMID- 12238874
TI  - Diaphragmatic fenestration for resistant pleural effusions after univentricular
      repair.
AB  - A 12-year-old child with chronic pleural effusions for a month and a half after a
      fenestrated Fontan operation underwent bilateral diaphragmatic fenestrations with
      complete relief. We suggest this approach as an alternative treatment for chronic
      pleural effusions that may ensue after total cavopulmonary connection.

PMID- 12238875
TI  - Cavernous hemangioma of the rib.
AB  - A 59-year-old man with an enlarged left chest wall mass that had been followed up
      for 3 years underwent surgical resection. The mass was pathologically diagnosed
      as cavernous hemangioma of the rib. This is the fourth case of this rare disease
      to be reported. However, it suggests that hemangioma of the rib should be
      considered in the differential diagnosis of rib tumors, especially in
      asymptomatic patients.

PMID- 12238876
TI  - Unusual imaging of late postpneumonectomy empyema.

PMID- 12238877
TI  - Aortic rupture after stenting of a native coarctation in an adult.

PMID- 12238878
TI  - Prosthetic aortic graft cannulation: a simple technique to secure hemostasis.
AB  - Securing the arterial cannulation site in a prosthetic aortic graft with a
      standard pursestring suture may be difficult and can lead to troublesome
      bleeding. We describe a simple technique to secure the cannulation site that
      avoids these problems.

PMID- 12238879
TI  - Coronary artery bypass via diaphragmatic approach with free graft.
AB  - To avoid injury to patent bypass grafts or myocardium during median sternotomy in
      coronary artery bypass graft reoperation, we performed modified minimally
      invasive direct coronary artery bypass to the right coronary artery via
      diaphragmatic approach using the right gastroepiproic artery. In cases in which
      the right gastroepiproic artery cannot be used, this technique is performed with
      a free graft from the gastroduodenal artery. This approach is very useful for
      reoperation in these circumstances.

PMID- 12238880
TI  - A technique to protect an axillo-coronary bypass graft.
AB  - We describe a simple technique to protect an axillo-coronary bypass graft with a
      stretch, thin-walled 6-mm polytetrafluoroethylene graft with removable rings.

PMID- 12238881
TI  - Sternal closure using semirigid fixation with thermoreactive clips.
AB  - Sternomy represents the standard approach to the heart and great vessels in most
      cardiothoracic procedures. Closure of this incision is simple; however, healing
      complications such as dehiscence, osteomyelitis, mediastinitis, and superficial
      wound infection or fistula may occur. We describe an alternative technique for
      sternal closure using semirigid fixation with thermoreactive clips.

PMID- 12238882
TI  - Anomalous origin of the left coronary artery from the pulmonary artery:
      collective review of surgical therapy.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery is an
      extremely rare but potentially fatal congenital coronary anomaly. Prompt surgical
      reestablishment of a two-coronary system on diagnosis yields excellent results
      and allows progressive and nearly total myocardial recovery. Follow-up of all
      patients is required to assess the adequacy of repair and to exclude ongoing or
      recurrent myocardial insult.

PMID- 12238883
TI  - 35 years of experimental research in transmyocardial revascularization: what have
      we learned?
AB  - In the past 35 years many experimental studies have been performed to investigate
      the revascularization potential of transmyocardial revascularization and the
      possible working mechanisms underlying the observed clinical improvement in
      angina pectoris after this treatment. In this review of the experimental
      literature, the various methods that have been used to create transmyocardial
      channels and the most supported hypotheses on the working mechanism (channel
      patency, angiogenesis and myocardial denervation) are discussed and evaluated.

PMID- 12238884
TI  - As originally published in 1996. Usefulness of pulsatile bidirectional
      cavopulmonary shunt in high-risk Fontan patients. Updated in 2002.
AB  - BACKGROUND: A bidirectional cavopulmonary shunt has been performed for the high
      risk Fontan patient. It is well known that in the presence of the bidirectional
      cavopulmonary shunt alone to secure pulmonary blood flow, the central pulmonary
      artery size decreases over time. We have performed pulsatile bidirectional
      cavopulmonary shunt (PBCPS), keeping pulmonary blood flow from the ventricle
      through the stenotic pulmonary valve, or a Blalock-Taussig shunt in patients who
      do not meet the criteria for the Fontan operation. METHODS: Eleven patients who
      underwent PBCPS between 1989 and 1993 were reviewed. We compared the results of
      cardiac catheterization immediately before PBCPS and during the postoperative
      observation period (310 +/- 257 days). RESULTS: Pulmonary blood flow and arterial
      oxygen saturation increased significantly after PBCPS (p = 0.01). Pumonary artery
      area index showed a tendency to increase (p = 0.11). The mean number of risk
      factors for the Fontan procedure decreased significantly from 1.8 +/- 1.1 to 0.7
      +/- 0.8 after PBCPS (p < 0.05). Overall, 5 of the 11 patients (45.5%) met the
      criteria for the Fontan procedure, and a fenestrated Fontan procedure was carried
      out in 4 of them. CONCLUSIONS: The PBCPS is useful for high-risk Fontan patients
      not only in the staged Fontan operation, but also as definitive palliation.

PMID- 12238885
TI  - The diseased statues.

PMID- 12238886
TI  - Coarctation of the lower thoracic aorta.

PMID- 12238887
TI  - Right coronary arteries that course between aorta and pulmonary artery.

PMID- 12238888
TI  - Vineberg operation combined with growth factor implantation.

PMID- 12238889
TI  - Aspects of human parasites in which surgical intervention may be important.
AB  - Until recently, physicians and surgeons in developed countries only occasionally
      encountered patients with parasitic protozoan and helminthic infections. High
      speed travel, immigration and the popularity of the tropics as vacation areas
      have increased the number of people at risk for parasitic disease. This chapter
      examines the significant literature on a select number of protozoan and
      helminthic parasites for which surgical intervention is important in the
      diagnosis, treatment or cure of the disease. Although traditional surgical
      approaches are covered, emphasis is placed on recent advances in the areas of
      transplantation and minimally invasive surgery. Combining the disciplines of
      parasitology and surgery, this chapter covers three protozoan and seven
      helminthic parasites for which surgery is a valid treatment option based on the
      frequency of cases reported in the literature. Following coverage of the selected
      parasites, a table is included listing additional helminths for which surgery
      contributes to patient management. Physicians in the USA, UK, and Europe need to
      be more aware of the presentation and treatment of parasitic infections. It is
      our sincere hope that this review accomplishes that goal, and ultimately benefits
      the patients we serve.

PMID- 12238890
TI  - Cestode parasites: application of in vivo and in vitro models for studies on the
      host-parasite relationship.
AB  - Cestode worms, commonly also known as 'flat' worms or tapeworms, are an important
      class of endoparasitic organisms. In order to complete their life cycle, they
      infect intermediate and definitive hosts in succession, through oral ingestion of
      eggs or larvae, respectively. Serious disease in humans or other mammalian hosts
      is mostly caused by the larval stages. Echinococcus spp. and Taenia spp. have
      been extensively investigated in the laboratory due to the fact that they
      represent important veterinary medical challenges and also cause grave diseases
      in humans. In contrast, Hymenolepis spp. and Mesocestoides spp. infections are
      relatively rare in humans, but these parasites have been extensively studied
      because their life cycle stages can be easily cultured in vitro, and can also be
      conveniently maintained in laboratory animal hosts. Thus they are more easily
      experimentally accessible, and represent important models for investigating the
      various aspects of cestode biology. This review will focus on in vitro and in
      vivo models which have been developed for studies on the host-parasite
      relationship during infection with Echinococcus, Taenia, Hymenolepis,
      Mesocestoides and Spirometra, and will cover the use of these models to
      investigate the morphology and ultrastructure of respective genera, the
      immunological relationship with the host and the development of vaccination
      approaches, as well as applications of these models for studies on parasite
      metabolism, physiology and gene expression. In addition, the use of these models
      in the development of chemotherapeutic measures against cestode infections is
      reviewed.

PMID- 12238891
TI  - Electron-transfer complexes in Ascaris mitochondria.
AB  - Parasites have developed a variety of physiological functions necessary for their
      survival within the specialized environment of the host. Using metabolic systems
      that are very different from those of the host, they can adapt to low oxygen
      tension present within the host animals. Most parasites do not use the oxygen
      available within the host to generate ATP, but rather employ anaerobic metabolic
      pathways. In addition, all parasites have a life cycle. In many cases, the
      parasite employs aerobic metabolism during its free-living stage outside the
      host. In such systems, parasite mitochondria play diverse roles. In particular,
      marked changes in the morphology and components of the mitochondria during the
      life cycle are very interesting elements of biological processes such as
      developmental control and environmental adaptation. Recent research on the
      respiratory chain of the parasitic helminth Ascaris suum has shown that the
      mitochondrial NADH-fumarate reductase system plays an important role in the
      anaerobic energy metabolism of adult parasites inhabiting hosts, as well as
      describing unique features of the developmental changes that occur during its
      life cycle.

PMID- 12238892
TI  - Developing a science of nursing education: innovation with research.

PMID- 12238893
TI  - "She asked this simple question": reflecting and the scholarship of teaching.

PMID- 12238895
TI  - Literary pedagogy in nursing: a theory-based perspective.
AB  - Using fictional and autobiographical literature in nursing education is a primary
      way of understanding patients' lived experiences and fostering development of
      essential relational and reflective thinking skills. Application of literary
      theory to this pedagogic practice can expand conceptualization of teaching goals,
      inform specific teaching strategies, and potentially contribute to socially
      consequential educational outcomes. This article describes a theoretical schema
      that focuses on pedagogical goals in terms of the three related skills (i.e.,
      reading, interpretation, criticism) of textual competence.

PMID- 12238894
TI  - Life circle: creating safe space for educational empowerment.

PMID- 12238896
TI  - Using storytelling as an approach to teaching and learning with diverse students.
AB  - Storytelling is an approach to teaching and learning that develops from the lived
      experiences ofteachers, clinicians, and students. This article examines
      thestorytelling process used to help students explore personal roles and make
      sense of their lives, and as an approach to help diverse undergraduate students
      with various learning styles.

PMID- 12238897
TI  - Beyond behavioral skills to human-involved processes: relational nursing practice
      and interpretive pedagogy.
AB  - This article argues that the teaching of behavioral communication skills may
      interfere with the learning of humanistic nursing practice. By inviting readers
      to consider moving beyond a method approach, the author discusses the pedagogical
      value of interpretive inquiry for the teaching-learning of relational practice.
      The author asserts that, as a "nonmethod," a pedagogy of interpretive inquiry can
      create opportunities for nursing students to learn and experience the
      transformative power of relationship, gain confidence in their capacity for
      relational being and a sense of trust in their ability to be with people in ways
      that are authentic and meaningful, and develop their overall ability to enact
      humanistic, relational nursing.

PMID- 12238898
TI  - Learning to lecture: exploring the skills, strategies, and practices of new
      teachers in nursing education.
AB  - A common experience among new teachers is learning how to lecture. Lecturing is a
      skill, a strategy, and a practice. As a skill, lecturing is learned over time.
      For example, teachers learn how to select content to hold students' attention.
      Lecturing is a strategy teachers use when they want to efficiently cover a great
      deal of content. In addition, it is a practice that has shared meanings,
      practical knowledge, and language. Exploring how new teachers learn to lecture
      clarifies the nature, meaning, and significance of lecturing in nursing
      education. The study described in this article used Heideggerian hermeneutic
      analyses to explicate the common experiences (i.e., themes and patterns) of new
      nurse teachers. Learning to Lecture as a theme is described, and implications for
      teacher preparation and future research are offered.

PMID- 12238899
TI  - Merging reflective inquiry and self-study as a framework for enhancing the
      scholarship of teaching.
AB  - This article provides a model for improving teaching practice and developing new
      knowledge about teaching. The reflective self-study approach to pedagogical
      inquiry is rooted in reflective inquiry and self-study as found in nursing and
      education literature, respectively. The model offers nurse educators a mechanism
      by which they can better understand themselves as teachers and how their teaching
      affects students. Essential features of the model include interdisciplinarity and
      collaboration. Using the framework outlined in this article will help establish
      reflective self-study research as an accepted model of inquiry and further the
      dialogue on teaching in higher education.

PMID- 12238900
TI  - Humor in clinical nursing education.

PMID- 12238901
TI  - Learning professionalism by celebrating students' work.

PMID- 12238902
TI  - A boy with long-lasting fever and poor hair growth.

PMID- 12238903
TI  - Prevention of accidents and injuries in Taiwan: an unfulfilled hope.

PMID- 12238904
TI  - A call for establishing a Children's Environmental Health Information Resource in
      Taiwan.
AB  - A tragic case of 7 years old child who suffered from injury caused by chemical
      burn of esophagus uncovered an urgent need of public education on the labeling of
      reused medicine bottle. The sad fact is that the case presented in the article or
      similer cases which occurred in the past in children is largely preventable. This
      article makes a plead to pediatricians that as the guardians of children, we have
      an inevitable responsibility of educating the public about the prevention of
      chemical injury. To achieve this goal, by using the information recently
      available from the Center of Disease Control (CDC) of the United States. I
      suggest several possible steps that we can take to establish a Children's
      Environmental Health Information Resource in Taiwan.

PMID- 12238905
TI  - A comparison of terbutaline and fenoterol unit dose vials in treating children
      with acute asthmatic attacks.
AB  - To compare the bronchodilation and adverse effects of two commercially marketed
      short-acting beta2-adrenergic agonists, terbutaline (Bricanyl, 5.0 mg/2ml) and
      fenoterol (Berotec,1.25 mg/2ml) unit dose vials (UDV), 108 acute asthmatic
      children, aged 5 to 14, were randomly enrolled into this study. Nebulization
      treatment for 10 minutes using an air compressor nebulizer was performed after
      measurements of baseline spirometry, SaO2, blood pressure and pulse rate. Same
      measurements were repeated at 0, 5, 15 and 30 minutes after the end of the
      nebulization treatment. The blood pressure was also monitored immediately and 30
      minutes after treatment. Almost all the spirometric parameters of both treatments
      at various time points significantly improved. The pulse rate significantly
      increased at 15 and 30 min. The SaO2 significantly increased at 30 min. The
      systolic blood pressure significantly decreased immediately (terbutaline only)
      and at 30 min (fenoterol only). No significant change was found in diastolic
      blood pressure. When the laboratory parameters at the same time points were
      compared. Significant better results for fenoterol treatment were found in FEV,
      at 30 min (p = 0.048), PEF at 15 and 30 min (p = 0.049 and p = 0.027,
      respectively), FEF25-75% at 30 min (p = 0.033), mean absolute increase of PEF at
      15 min (p = 0.034) and 30 min (p = 0.021), FEF25-75% at 30 min (p = 0.046), and
      in mean percent increase of FEF25-75% at 30 min (p = 0.047). The adverse effects
      for both groups were almost equal and around 21%. In conclusion, both terbutaline
      and fenoterol UDV nebulization treatments are effective in treating acute
      asthmatic children. The adverse effects are nearly equal. The fenoterol UDV
      nebulization treatment shows a little better result in improving pulmonary
      function than does terbutaline.

PMID- 12238906
TI  - A comparison of survival in extremely low birth weight infants between periods
      1997-1998 and 1998-2000.
AB  - The survival rates and the influential perinatal factors of extremely low birth
      weight (ELBW) infants were compared between two periods, including January 1997
      through May 1998 (Period 1, n = 84) and June 1998 through December 2000 (Period
      2, n = 145). The survival rate was 48.8% (41/84) during Period 1 and 55.2%
      (80/145) during Period 2. Gestational age (GA) and birth weight (BW) were the
      most important factors that influenced the survival rate. The cut off levels,
      below which mortality rates increased significantly, were GA < 24 weeks and BW <
      700 gm during Period 1 and GA < 24 weeks and BW < 500 gm during Period 2. During
      Period 1, the smallest survival was a female infant with GA of 23 weeks and BW of
      530 gm who had no complication and lived well. During Period 2, the smallest
      survival was a female infant with GA of 21 weeks and BW of 460 gm who was
      discharged with home oxygen therapy. She was admitted again via emergency due to
      sudden onset of apnea and cardiac arrest 4 days after discharge, and she died 4
      days after the 2nd admission. Our results did not show any advantages to maternal
      transfer or delivery by Cesarean section. The early neonatal mortality rate was
      still high during Period 2 and accounted for 50% of the overall neonatal
      mortality rate. This implies that further training to improve the neonatal care,
      especially during the early stage of the first week should be reinforced to
      reduce neonatal deaths. Prevention of the births of extremely premature infants
      should be more emphasized to decrease neonatal mortality and morbidity rates.
      When the delivery of an ELBW infant is impending, an active plan of treatment for
      all infants of GA > or = 24 weeks or BW > or = 500 gm seems appropriate.

PMID- 12238907
TI  - Clinical analysis of necrotizing enterocolitis with intestinal perforation in
      premature infants.
AB  - To identify the prognostic factors correlating with the outcome of the perforated
      necrotizing enterocolitis (NEC), the charts of 20 premature infants with
      perforated NEC were reviewed. Eight patients had long-term survival and 12 died.
      Infants in the survival group had significantly lower incidence of starting to
      feed before perforation, patent ductus arteriosus, indomethacin use, acidosis,
      and shock. Sepsis was only found in the group of infants that died The survival
      group were diagnosed with NEC and intestinal perforation at an earlier age than
      the infants that died. The time from diagnosis of NEC to intestinal perforation
      was longer in the infants that died. The localization of necrosis from
      operativefindings were all confined to the ileum-cecum area in survival group.
      The infants in the survival group were likely to have a single perforation. In
      addition, according to the operative management, they were divided into three
      groups: Group I consisted of six patients who received peritoneal drainage only,
      group II consisted of three patients who received peritoneal drainage followed by
      laparotomy, and group In consisted of 11 patients who received primary
      laparotomy. Infants in groups I and II had significantly lower gestational ages
      and birth weights than group III. There were no significant differences in
      mortality rates among infants in groups I, II and III. We concluded that the
      factors including prior enteral feeding, patent ductus arteriosus, indomethacin
      use, acidosis, sepsis, shock, delayed onset of NEC and perforation, multiple
      perforation, and diffuse necrotic changes were significant prognostic factors of
      poor outcome. Peritoneal drainage was a resuscitative procedure in critical
      condition and laparotomy should mostly be considered as the final treatment in
      the infants with perforated NEC.

PMID- 12238908
TI  - A proposal of screening guideline for retinopathy of prematurity in Taiwan.
AB  - Retinopathy of prematurity (ROP) is one of the most important morbidity in
      premature infants. The latest American Academy of Pediatrics (AAP) screening
      guidelines for ROP are mandatory for infants with birth weights < or = 1500 g or
      gestational ages (GA) < or = 28 weeks. To determine the appropriate upper limits
      for ROP screening in Taiwan in terms of birth weight and gestational age, we
      performed a retrospective review of all 617 infants who were born at the National
      Taiwan University Hospital from January 1, 1994 to December 31, 1999, and
      survived beyond 28 days of life and received eye-ground evaluation under our
      current ROP screening guidelines. From the start of our study, the criteria for
      screening was birth weight <2000 g or gestational age < 35 weeks. The maximal
      stage of retinopathy observed was recorded. We found no ROP greater than stage I
      in infants with birth weights > 1500g and GA > 31 weeks. In comparing with our
      current guidelines, lowering the screening criteria to birth weight < or = 1500g
      or gestational age < or = 31 weeks reduced the number of infants requiring
      screening by 37.2%, while no case of ROP greater than stage 1 was missed.
      However, five cases of stage 2 ROP would have been missed in our study if the
      gestational age cut-off was < or = 28 weeks as recommended by AAP. Therefore, we
      recommend that in the tertiary nursery in Taiwan, the gestational age < or = 31
      weeks or birth body weight < or = 1500 g should be screened for ROP regardless of
      clinical condition. The screening for larger infants with high risk of ROP
      requires further discretion of the attending physicians.

PMID- 12238909
TI  - Schizencephaly: correlation between clinical and neuroimaging features.
AB  - Schizencephaly is an uncommon congenital brain malformation. We report our
      experience of 13 patients with schizencephaly and evaluate the clinical,
      neuroradiologic, electroencephalographic (EEG), and nosological features. Of
      these 13 patients, 8 were unilateral forms, 5 were bilateral forrms and 11 were
      open-lip type schizencephaly. One patient was proven to have cytomegalovirus
      (CMV) infection. The clinicalfeatures and neurodevelopmental outcomes are
      variable. Although seizure developed in 9 patients (5 patients from unilateral
      and 4 from bilateral forms), the severity of epilepsy was not totally related to
      the degree of malformations. The neurodevelopmental outcome depended on the
      extent of schizencephaly as well as the seizure control. Those with bilateral
      forms and intractable seizures had the worst outcome. Other central nervous
      system (CNS) anomalies were observed in 11 patients. Six out of 11 patients had
      focal cortical dysplasia. We conclude that children with schizencephaly usually
      have variable neurological impairment. Earlier diagnosis of schizencephaly and
      related CNS malformation with neuroimaging is helpful in predicting the
      neurodevelopmental outcomes in these patients.

PMID- 12238910
TI  - Total parenteral nutrition as a primary therapeutic modality for congenital
      chylous ascites: report of one case.
AB  - Congenital chylous ascites in the neonatal period is a rare entity. It is
      primarily related to congenital abnormalities of the lymphatics. We present a
      case in which ascites was detected by prenatal ultrasonogram. No evidence of
      congenital cytomegalovirus infection, intrauterine meconium peritonitis, or
      intestinal or genitourinary system abnormalities was found. Congenital chylous
      ascites was confirmed via an abdominal sonogram and diagnostic paracentesis.
      After 26 days of NPO and total parenteral nutrition, the newborn hadfully
      recovered.

PMID- 12238911
TI  - Infected cephalohematoma complicated with meningitis: report of one case.
AB  - Infected cephalohematoma associated with meningitis is rarely reported. We report
      the case of 19-day-old female newborn with a cephalohematoma infected by
      Escherichia coli, and whose cerebrospinal fluid showed pleocytosis. Antibiotics
      alone could not eradicate the infection of the cephalohematoma, and surgical
      incision and drainage resulted in obvious clinical improvement. Three weeks of
      antibiotic usage completed the course of treatment.

PMID- 12238912
TI  - Schwartz-Jampel syndrome: report of one case.
AB  - We report a case of Schwartz-Jampel syndrome in a 2-year-9-month-old Taiwanese
      girl and her clinical response to treatment. She had a history of generalized
      muscle stiffness and hypertrophy since birth. Clinical and electromyographic
      myotonia were noted. Other clinical features included short stature, unusual
      facial appearance, ophthalmoplegia, elbow joint contractures, and developmental
      hip dysplasia. Muscle stiffness and myotonia improved after infusion of
      lidocaine. She then received oral mexiletine and the symptoms significantly
      improved.

PMID- 12238913
TI  - Megacystis microcolon intestinal hypoperistalsis syndrome with severe psychomotor
      retardation: report of one case.
AB  - Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare and
      severe form of neonatal functional bowel obstruction. Affected neonates present
      with vomiting, an overdistended abdomen, and a huge bladder after birth, and they
      usually die early in life despite intensive medical and/or surgical management.
      We report the case of a girl aged 3 years 7 months who had MMIHS with severe
      psychomotor retardation; autopsy was performed after her death.

PMID- 12238914
TI  - 6-Aryl-1,4-dihydro-benzo[d][1,3]oxazin- 2-ones: a novel class of potent,
      selective, and orally active nonsteroidal progesterone receptor antagonists.
AB  - Novel 6-aryl-1,4-dihydro-benzo[d][1,3]oxazin-2-ones were synthesized and tested
      as progesterone receptor (PR) antagonists. These compounds were potent and showed
      good selectivity for PR over other steroid receptors such as the glucocorticoid
      and androgen receptors (e.g., greater than 80-fold selectivity at PR for 4h).
      Numerous 6-aryl benzoxazinones (e.g., 4h-j) were active orally in the uterine
      decidualization and component C3 assays in the rats. In these in vivo models,4h
      had potencies comparable to mifepristone.

PMID- 12238915
TI  - Ethyl (3S,4aR,6S,8aR)-6-(4-ethoxycar- bonylimidazol-1-ylmethyl)decahydroiso
      quinoline-3-carboxylic ester: a prodrug of a GluR5 kainate receptor antagonist
      active in two animal models of acute migraine.
AB  - Amino diacid 3, a highly selective competitive GluR5 kainate receptor antagonist,
      exhibited high GluR5 receptor affinity and selectivity over other glutamate
      receptors. Its diethyl ester prodrug 4 was orally active in two models of
      migraine: the neurogenic dural plasma protein extravasation model and the nucleus
      caudalis c-fos expression model. These data suggest that a GluR5 kainate receptor
      antagonist might be an efficacious antimigraine therapy with a novel mechanism of
      action.

PMID- 12238916
TI  - New templates for syntheses of ring-fused, C(10) beta-turn peptidomimetics
      leading to the first reported small-molecule mimic of neurotrophin-3.
AB  - beta-Turn peptidomimetics 1 were designed to mimic hot spots of neurotrophin-3
      (NT-3) and others. Solid-phase syntheses of these were developed, though
      limitations were encountered with scale-up. Consequently, an alternative design
      with 2 was investigated. 1 and 2 favored distorted type I beta-turn conformations
      in solution. It was found that peptidomimetic 2b has NT-3-like neurotrophic
      activity in cell survival assays, selectively binds the NT-3 receptor TrkC, and
      induces the tyrosine phosphorylation of the TrkC receptor.

PMID- 12238917
TI  - A new, potent urotensin II receptor peptide agonist containing a Pen residue at
      the disulfide bridge.
AB  - Replacing Cys(5) by Pen (penicillamine, beta,beta-dimethylcysteine) in the cyclic
      C-terminal U-II octapeptide, U-II(4-11), we have obtained a potent urotensin II
      (U-II) receptor agonist. Conformational analysis of solution NMR data indicated
      that the putative biologically active conformation of U-II is stabilized by
      introduction of a Pen residue. To the best of our knowledge, this is the most
      potent U-II receptor agonist reported to date.

PMID- 12238918
TI  - N-[3-(1H-imidazol-4-ylmethyl)phenyl]ethanesulfonamide (ABT-866, 1),(1) a novel
      alpha(1)-adrenoceptor ligand with an enhanced in vitro and in vivo profile
      relative to phenylpropanolamine and midodrine.
AB  - N-[3-(1H-Imidazol-4-ylmethyl)phenyl]ethanesulfonamide (ABT-866, 1) is a novel
      alpha(1) agent having the unique profile of alpha(1A) (rabbit urethra, EC(50) =
      0.60 microM) agonism with alpha(1B) (rat spleen, pA(2) = 5.4) and alpha(1D) (rat
      aorta, pA(2) = 6.2) antagonism. An in vivo dog model showed 1 to be more
      selective for the urethra over the vasculature than A-61603 (2), ST-1059 (3, the
      active metabolite of midodrine), and phenylpropanolamine (4).

PMID- 12238919
TI  - A sorbitol dehydrogenase inhibitor of exceptional in vivo potency with a long
      duration of action: 1-(R)-[4-[4-(4,6-dimethyl[1,3,5]triazin-2-yl)- 2R,6S
      dimethylpiperazin-1-yl]pyrimidin-2- yl]ethanol.
AB  - We report here a novel sorbitol dehydrogenase inhibitor, 16, that shows very high
      oral potency (50 microg/kg) in normalizing elevated fructose levels in the
      sciatic nerve of chronically diabetic rats and sustained duration of action (>24
      h). Furthermore, 16 shows attractive pharmaceutical properties, including good
      solubility in simulated human gastric fluid, excellent Caco-2 Papp, moderate
      lipophilicity, and metabolic stability for achieving good oral absorption and
      long duration of action.

PMID- 12238920
TI  - General pseudoreceptor model for sweet compounds: a semiquantitative prediction
      of binding affinity for sweet-tasting molecules.
AB  - The chemical structures of sweet compounds are very different, ranging from
      sugars to amino acids and peptides or other compounds such as saccharin. The
      biological mechanism underlying the generation of sweet taste is still unknown,
      although in the past few years much research has provided evidence for the
      existence of a true chemoreception process, mediated by receptor proteins on the
      taste buds. In particular, the initial step of the process involves the
      reversible binding of the sweet compounds to their receptor(s). In this work, we
      have investigated this binding via a pseudoreceptor model, which has been
      developed using a training set of 24 compounds belonging to different families
      including sugars, peptides, and other intensive sweeteners. This model provided a
      correlation coefficient (r(2)) of 0.985 between the calculated and the
      experimental free energies of binding, which are related to the molar relative
      sweetness, for the training set and is able to predict semiquantitatively free
      energies of ligand binding for an independent set of five test ligand molecules
      within 0.3-2.1 kcal mol(-1) of the experimental values.

PMID- 12238921
TI  - Angiotensin II vs its type I antagonists: conformational requirements for
      receptor binding assessed from NMR spectroscopic and receptor docking
      experiments.
AB  - The conformations of three angiotensin II (AII) peptide antagonists ([Sar1]-AII(1
      7)-NH(2), [Sar1,Val5,Ala8]-AII and the AII antipeptide, [Glu1,Gly2,Val5,Val8]
      AII) were assessed in a lipid medium. A common backbone turn was identified
      through modeling and spectroscopic studies. The His6 residue acted as a pivoting
      point beyond which each peptide adopted two distinct conformations. One principle
      conformer resembled that previously determined for AII while the other was
      designated as an AII antagonist like conformer. A computational overlay between
      the nonpeptide antagonist, Losartan, and both the AII and the AII like
      conformation of [Sar1,Val5,Ala8]-AII revealed common pharmacophoric points with
      RMS deviations between 1 and 1.5 A. Both the AII conformer and the AII antagonist
      like conformer of [Sar1,Val5,Ala8]-AII were docked into a model of the AT(1)
      receptor. Receptor residue Phe289 and Asp281 provided good contact points for
      both peptides. Some differences were also noted. The terminal carboxyl of AII
      contacted Lys199 of the receptor while that of [Sar1,Val5,Ala8]-AII bridged Arg23
      at the top of helix 1. The Asp1 side chain of AII interacted with His183 of the
      receptor.

PMID- 12238922
TI  - Unique overlap in the prerequisites for thrombin inhibition and oral
      bioavailability resulting in potent oral antithrombotics.
AB  - Despite intense research over the last 10 years, aided by the availability of X
      ray structures of enzyme-inhibitor complexes, only very few truly orally active
      thrombin inhibitors have been found. We conducted a comprehensive study starting
      with peptide transition state analogues (TSA). Both hydrophobic nonpeptide
      analogues as well as hydrophilic peptidic analogues were synthesized. The
      bioavailability in rats and dogs could be drastically altered depending on the
      overall charge distribution in the molecule. Compound 27, a tripeptide TSA
      inhibitor of thrombin, showed an oral bioavailability of 32% in rats and 71% in
      dogs, elimination half-lives being 58 and 108 min, respectively. The thrombin
      inhibition constant of compound 27 was 1.1 nM, and in an in vivo arterial flow
      model, the ED(50) was 5.4 nmol/kg.min, comparable to known non-TSA inhibitors. A
      molecular design was found that combines antithrombotic efficiency with oral
      bioavailability at low dosages.

PMID- 12238924
TI  - Discovery and SAR of a novel selective and orally bioavailable nonpeptide
      classical competitive inhibitor class of protein-tyrosine phosphatase 1B.
AB  - Reversible phosphorylation and dephosphorylation of key proteins on tyrosine
      residues are important parts of intracellular signaling triggered by hormones and
      other agents. Recent knock-out studies in mice have identified PTP1B as a
      potential target for the treatment of diabetes and obesity. As a consequence, a
      number of academic and industrial groups are aggressively pursuing the
      development of selective PTP1B inhibitors. In addition, other protein-tyrosine
      phosphatases (PTPs) appear to be critically involved in major diseases such as
      cancer and autoimmunity. Given the diversity of PTPs and their potential as drug
      targets in different diseases, we have taken a broad approach to develop active
      site-directed selective inhibitors of specific members of this family of enzymes.
      Using a high throughput screening, we have previously identified 2
      (oxalylamino)benzoic acid 3a as a relatively weak but classical competitive
      inhibitor of several PTPs.(4) On the basis of our early studies, indicating that
      3a might be used as a starting point for the synthesis of selective PTP
      inhibitors, we now present our efforts in expansion of this concept and provide
      here a number of new chemical scaffolds for the development of inhibitors of
      different members of the PTP family. Although the core structure of these
      inhibitors is charged, good oral bioavailability has been observed in rat for
      some compounds. Furthermore, we have observed enhancement of 2-deoxy-glucose
      accumulation in C2C12 cells with prodrug analogues.

PMID- 12238923
TI  - Novel potent AMPA/kainate receptor antagonists: synthesis and anticonvulsant
      activity of a series of 2-[(4-alkylsemicarbazono)-(4-amino-phenyl)methyl]-4,5
      methylenedioxyphenylacetic acid alkyl esters.
AB  - In this paper we describe the synthesis of a series of novel 2-[(4
      alkylsemicarbazono)-(4-aminophenyl)-methyl]-4,5-methylenedioxyphenylacetic acid
      alkyl esters (10-19) carrying an alkylsemicarbazono moiety at a benzylic site.
      The influence of this group on the biological activity was evaluated by testing
      the corresponding derivatives 20-22 in which the 4-alkylsemicarbazono moiety was
      removed (compound 20) or its alkylureido portion shifted at position 1 (compounds
      21-22). Furthermore, the involvement of the 4-aminobenzyl moiety in the
      anticonvulsant activity was evaluated by testing derivative 23. The
      anticonvulsant activity of all compounds was assayed against audiogenic seizures
      induced in DBA/2 mice. Within this series of derivatives, 2-[(4-aminophenyl)-(4
      methylsemicarbazono)-methyl]-4,5-methylenedioxyphenylacetic acid methyl ester
      (10) proved to be the most active compound. It displayed a potency 5-fold higher
      than that shown by 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3
      benzodiazepine (1, GYKI 52466), a well-known noncompetitive 2-amino-3-(3-hydroxy
      5-methylisoxazol-4-yl)propionic acid (AMPA) receptor antagonist. Compound 10 was
      also effective in suppressing seizures induced in Swiss mice by maximal
      electroshock (MES) or pentylenetetrazole (PTZ). Furthermore, it antagonized in
      vivo seizures induced by icv administration of AMPA or kainate (KA). Using the
      patch-clamp technique in primary cultures of granule neurons we tested compounds
      10 and 21 for their ability to modulate currents evoked by KA and 2-amino-3-(3
      hydroxy-5-tert-butylisoxazol-4-yl)propionic acid (ATPA). These two derivatives
      reduced KA and ATPA currents to a larger extent than that shown by reference
      compound 1. Compounds 10 and 21 were also able to reduce neuronal cell death
      induced by the application of KA (100 microM).

PMID- 12238925
TI  - Interaction of designed sulfated flavanoids with antithrombin: lessons on the
      design of organic activators.
AB  - Recently, we designed (-)-epicatechin sulfate (ECS), the first small
      nonsaccharide molecule, as an activator of antithrombin for the accelerated
      inhibition of factor Xa, a key proteinase of the coagulation cascade (Gunnarsson,
      G. T.; Desai, U. R. J. Med. Chem. 2002, 45, 1233-1243). Although sulfated
      flavanoid ECS was found to bind antithrombin with an affinity ( approximately
      10.7 microM) comparable to the reference trisaccharide DEF ( approximately 4.5
      microM), it accelerated the inhibition of factor Xa only 10-fold as compared to
      the approximately 300-fold observed with DEF. To determine whether this
      conformational activation of the inhibitor is dependent on the structure of the
      organic activator and to probe the basis for the deficiency in activation, we
      studied the interaction of similar sulfated flavanoids with antithrombin. (+)
      Catechin sulfate (CS), a chiral stereoisomer of ECS, bound plasma antithrombin
      with a 3-fold higher affinity (K(D) = 3.5 microM) and a 2-fold higher second
      order rate constant for factor Xa inhibition (k(ACT) = 6750 M(-1) s(-1)). On the
      contrary, the K(D) and k(ACT) were found to be lower approximately 7.4- and
      approximately 2.4-fold, respectively, for its racemic counterpart, (+/-)-catechin
      sulfate. Dependence of the equilibrium dissociation constant on the ionic
      strength of the medium at pH 6.0 and 7.4 suggests that nonionic interactions
      contribute a major proportion ( approximately 55-73%) of the total binding
      energy, and only 1-2 ion pairs, in comparison to the expected approximately 4 ion
      pairs for the reference trisaccharide, are formed in the interaction. Competitive
      binding experiments indicate that activator CS does not compete with a saccharide
      ligand that binds antithrombin in the pentasaccharide binding site, while it
      competes with full-length low-affinity heparin. A molecular docking study
      suggests plausible binding of CS in the extended heparin binding site, which is
      adjacent to the binding domain for the reference trisaccharide DEF. In
      combination, the results demonstrate that although conformational activation of
      antithrombin with small sulfated flavanoids is dependent on the structure of the
      activator, the designed activators do not bind in the pentasaccharide binding
      site in antithrombin resulting in weak activation. The mechanistic investigation
      highlights plausible directions to take in the rational design of specific high
      affinity organic antithrombin activators.

PMID- 12238926
TI  - Structural determinants of A(3) adenosine receptor activation: nucleoside ligands
      at the agonist/antagonist boundary.
AB  - Mutagenesis of the human A(3) adenosine receptor (AR) suggested that certain
      amino acid residues contributed differently to ligand binding and activation
      processes. Here we demonstrated that various adenosine modifications, including
      adenine substitution and ribose ring constraints, also contributed differentially
      to these processes. The ligand effects on cyclic AMP production in intact CHO
      cells expressing the A(3)AR and in receptor binding were compared. Notably, the
      simple 2-fluoro group alone or 2-chloro in combination with N(6)-substitution
      dramatically diminished the efficacy of adenosine derivatives, even converting
      agonist into antagonist. Other affinity-increasing substitutions, including N(6)
      (3-iodobenzyl) 4 and the (Northern)-methanocarba 15, also reduced efficacy,
      except in combination with a flexible 5'-uronamide. 2-Cl-N(6)-(3-iodobenzyl)
      derivatives, both in the (N)-methanocarba (i.e., of the Northern conformation)
      and riboside series 18 and 5, respectively, were potent antagonists with little
      residual agonism. Ring-constrained 2',3'-epoxide derivatives in both riboside and
      (N)-methanocarba series 13 and 21, respectively, and a cyclized (spiral) 4',5'
      uronamide derivative 14 were synthesized and found to be human A(3)AR
      antagonists. 14 bound potently at both human (26 nM) and rat (49 nM) A(3)ARs. A
      rhodopsin-based A(3)AR model, containing all domains except the C-terminal
      region, indicated separate structural requirements for receptor binding and
      activation for these adenosine analogues. Ligand docking, taking into account
      binding of selected derivatives at mutant A(3)ARs, featured interactions of TM3
      (His95) with the adenine moiety and TMs 6 and 7 with the ribose 5'-region. The 5'
      OH group of antagonist N(6)-(3-iodobenzyl)-2-chloroadenosine 5 formed a H-bond
      with N274 but not with S271. The 5'-substituent of nucleoside antagonists moved
      toward TM7 and away from TM6. The conserved Trp243 (6.48) side chain, involved in
      recognition of the classical (nonnucleoside) A(3)AR antagonists but not adenosine
      derived ligands, displayed a characteristic movement exclusively upon docking of
      agonists. Thus, A(3)AR activation appeared to require flexibility at the 5'- and
      3'-positions, which was diminished in (N)-methanocarba, spiro, and epoxide
      analogues, and was characteristic of ribose interactions at TM6 and TM7.

PMID- 12238927
TI  - Antitumor AHMA linked to DNA minor groove binding agents: synthesis and
      biological evaluation.
AB  - DNA minor groove binder hybrid molecules, netropsin derivatives such as N-[2
      (dimethylamino)ethyl]-1-methyl-4-aminopyrrolo-2-carboxamide (MePy) or its
      derivatives containing two units of N-methylpyrrolecarboxamide (diMePy) and
      bisbenzimidazole (Ho33258), were linked to the NH(2) function of AHMA or to the
      CH(2)OH group of AHMA-ethylcarbamate to form AHMA-N-netropsins (13-16) and AHMA
      ethylcarbamate-O-netropsins (19-22), and AHMA-bisbenzimidazole (AHMA-Ho33258,
      25), respectively. These conjugates' in vitro antitumor activity, inhibition of a
      variety of human tumor cell growth, revealed that AHMA-ethylcarbamate-O-netropsin
      derivatives were more cytotoxic than AHMA-N-netropsin compounds. In the same
      studies, all compounds bearing MePy were more potent than those compounds linked
      with diMePy. Moreover, AHMA-netropsin derivatives bearing a succinyl chain as the
      linking spacer were more potent than those compounds having a glutaryl bridge.
      Among these hybrid molecules, AHMA-ethylcarbamate-O-succinyl-MePy (19) was 2- to
      6-fold more cytotoxic than the parent compound AHMA (5) in various cell lines,
      whereas compound 25 had very poor solubility and was inactive. Studies on the
      inhibitory effect against topoisomerase II (Topo II) and DNA interaction of these
      conjugates showed no correlation between the potency of DNA binding and
      inhibitory activity against Topo II.

PMID- 12238928
TI  - Antimicrobial peptides: synthesis and antibacterial activity of linear and cyclic
      drosocin and apidaecin 1b analogues.
AB  - Drosocin and apidaecin Ib are two insect antimicrobial peptides showing a
      significant sequence homology and a common mechanism of action, which includes
      stereoselective elements but is devoid of any pore-forming activity. A
      substantial difference between the two peptides is the presence in the drosocin
      sequence of an O-glycosylated threonine residue, which is important for its
      antimicrobial activity. Through the synthesis of a series of differently
      glycosylated drosocin analogues, we have shown that the antimicrobial activity
      against several Gram-negative bacteria appears to be modulated by the sugar
      moiety (Gal vs GalNAc) and the type of glycosidic linkage (alpha-O-, beta-O-, or
      alpha-C-). The insertion of a glycosylated threonine residue in the apidaecin Ib
      sequence improves the sequence homology with drosocin but reduces the
      antimicrobial activity. To gain information on the possible bioactive
      conformation of these peptides, we synthesized an unglycosylated cyclic analogue
      of drosocin, containing an intrachain disulfide bond, and the head-to-tail cyclic
      analogues of drosocin and apidaecin, as well as their corresponding cyclic
      dimers. Only the large cyclic dimer of apidaecin partially retained the
      antimicrobial activity, suggesting that a bending of the peptide chain, in
      particular in the middle of the molecule, is not a structural element
      characteristic of the bioactive conformation of drosocin and apidaecin.
      Experiments aimed at testing the effect of selected drosocin and apidaecin
      peptides on biological membranes showed that some peptides display a moderate
      hemolytic activity and that a dissociation between antibacterial activity and
      cytotoxicity to eukaryotic cells can be achieved in differently glycosylated
      peptide analogues.

PMID- 12238929
TI  - Enhancement of nucleoside cytotoxicity through nucleotide prodrugs.
AB  - A common reason for the lack of cytotoxicity of certain nucleosides is thought to
      be their inability to be initially activated to the monophosphate level by a
      nucleoside kinase or other activating enzyme. In a search for other nucleosides
      that might be worthwhile anticancer agents, we have begun to examine the
      utilization of monophosphate prodrugs in order to explore whether any enhanced
      cytotoxicity might be found for the prodrugs of candidate nucleosides that have
      little or no cytotoxicity. To that end, 5'-bis(pivaloyloxymethyl) phosphate
      prodrugs of two weakly cytotoxic compounds, 8-aza-2'-deoxyadenosine (5) and 8
      bromo-2'-deoxyadenosine (9), have been prepared. These prodrugs (8 and 12) were
      examined for their cytotoxicity in CEM cells and were found to possess
      significantly enhanced cytotoxicity when compared with the corresponding parent
      nucleosides. Further cell culture experiments were conducted to gain insight into
      the mechanisms of cytotoxicity of these two prodrugs, and those data are
      reported.

PMID- 12238930
TI  - Potent and selective inhibitors of PDGF receptor phosphorylation. 2. Synthesis,
      structure activity relationship, improvement of aqueous solubility, and
      biological effects of 4-[4-(N-substituted (thio)carbamoyl)-1-piperazinyl]-6,7
      dimethoxyquinazoline derivatives.
AB  - 4-[4-(N-Substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline
      derivatives such as KN1022 are potent inhibitors of the phosphorylation of
      platelet derived growth factor receptor (PDGFR). Structure activity relationships
      in the (thio)urea moiety, the phenyl ring itself, the linker between these two
      moieties, and the piperazine moiety were investigated. The role of the linker was
      found to be quite different, where ureas yielded decreasing activity, while
      thioureas provided increasing activity. Cyanoguanidine as a bioisostere of
      thiourea and related dicyanovinyl or nitrovinyl groups were not suitable for
      potent activity. A hydrogen atom on the (thio)urea moiety was essential for
      activity. Stereochemistry was also important for inhibition of PDGFR
      phosphorylation. Through the modification of these moieties, benzylthiourea
      analogues with a small substituent on the 4-position and the 3,4-methylenedioxy
      group (KN734/CT52923) were found to be optimal for selective and potent activity.
      Replacement of the phenyl ring by heterocycles improved aqueous solubility
      without loss of activity and kinase selectivity. Introduction of a methyl group
      on 5-position of the piperazine ring and replacement by homopiperazine reduced
      inhibitory activity. An efficient synthetic method was also developed for 2
      pyridylurea-containing analogues, via carbonylation of 2-aminopyridine with N,N'
      carbonyldiimidazole. A potent analogue, KN734, inhibited smooth muscle cell
      proliferation and migration induced by platelet derived growth factor-BB (PDGF
      BB) and suppressed neointima formation following balloon injury in rat carotid
      artery by oral administration. Therefore, 4-[4-(N-substituted (thio)carbamoyl)-1
      piperazinyl]-6,7-dimethoxyquinazoline derivatives may be expected to have
      potential as therapeutic agents for the treatment of restenosis.

PMID- 12238931
TI  - Coupling of a competitive and an irreversible ligand generates mixed type
      inhibitors of Trypanosoma cruzi trypanothione reductase.
AB  - 9-Aminoacridines and (terpyridine)platinum(II) complexes are competitive and
      irreversible inhibitors, respectively, of trypanothione reductase from
      Trypanosoma cruzi, the causative agent of Chagas' disease. Four chimeric
      compounds in which 2-methoxy-6-chloro-9-aminoacridine was covalently linked to
      the (2-hydroxyethanethiolate)(2,2':6',2' '-terpyridine)platinum(II) complex were
      synthesized and studied as inhibitors of the parasite enzyme. The derivatives
      differed by the nature and/or the length of the spacer connecting the two
      aromatic systems. All four compounds were effective mixed type inhibitors of
      trypanothione reductase with K(i) and K(i)' values of 0.3-4 and 2-11 microM,
      respectively. The most potent inhibitor had an ethylthioether linkage between the
      two aromatic ring systems, and the other compounds contained an alkyl ether group
      with 4-6 methylene groups. In contrast to the parasite enzyme, human glutathione
      reductase, the closest related host enzyme was not inhibited by these compounds.
      The finding that the conjugation of a competitive and an irreversible inhibitor
      can give rise to reversible mixed type inhibitors underlines the difficulties
      associated with inhibitor design based on the three-dimensional structure of
      trypanothione reductase.

PMID- 12238932
TI  - Inactivation and inhibition of gamma-aminobutyric acid aminotransferase by
      conformationally restricted vigabatrin analogues.
AB  - Four cyclohexene analogues of gamma-aminobutyric acid (GABA) and beta-alanine
      were designed as conformationally rigid analogues of the epilepsy and drug
      addiction drug vigabatrin and as potential mechanism-based inactivators of gamma
      aminobutyric acid aminotransferase (GABA-AT). The corresponding cyclopentene
      analogues were previously reported to be inhibitors, but not inactivators, of
      GABA-AT (Qiu, J.; Pingsterhaus, J.; Silverman, R. B. J. Med. Chem. 1999, 42, 4725
      4728). cis-3-Aminocyclohex-4-ene-1-carboxylic acid (3) and cis-2-aminocyclohex-3
      ene-1-carboxylic acid (5) showed time- and concentration-dependent, irreversible
      inactivation of GABA-AT. In both cases, the inactivations are protected by
      substrate, indicating that they are active site-directed. trans-3-Aminocyclohex-4
      ene-1-carboxylic acid (4) and trans-2-aminocyclohex-3-ene-1-carboxylic acid (6)
      are not inactivators but are competitive reversible inhibitors of GABA-AT. Unlike
      the cyclopentene analogues, there appears to be sufficient ring flexibility to
      allow inactivation to occur. The orientation of the carboxylic and amino groups
      of these analogues is important for their binding to GABA-AT. Molecular modeling
      of GABA-AT with 3-6 and molecular dynamics simulations with vigabatrin bound
      provide rationalizations for the inhibitory properties of these compounds.

PMID- 12238933
TI  - Design, synthesis, and immunostimulatory properties of CpG DNAs containing alkyl
      linker substitutions: role of nucleosides in the flanking sequences.
AB  - Bacterial and synthetic DNA containing unmethylated CpG dinucleotides activate
      the innate immune system and promote Th1-like immune responses. Recently, a
      receptor, TLR9, has been shown to recognize CpG DNA and activate immune cascade.
      But there have been no reports on the molecular mechanisms of recognition between
      CpG DNA and the receptor(s). Our earlier studies described a number of the
      chemical and structural characteristics of CpG dinucleotide and the sequences
      flanking the CpG dinucleotide that are critical for immunostimulatory activity.
      In the present study, we examined the effect of the presence and absence of a
      nucleoside in the flanking sequences by replacing one or two natural
      deoxyribonucleosides at various positions with one or more alkyl- (C2-C12),
      branched alkyl- (glyceryl or aminobutyryl-propanediol), or ethyleneglycol- (tri
      or hexa) linkers. The results suggest that a linker substitution at the first two
      nucleoside positions adjacent to the CpG dinucleotide on the 5'- or the 3'-side
      neutralizes the immunostimulatory activity, as determined by in vitro mouse
      spleen cell proliferation, cytokine secretion, and in vivo mouse spleen
      enlargement. The same substitutions placed about three to six nucleotides away
      from the CpG dinucleotide either did not affect or potentiated immunostimulatory
      activity compared with parent CpG-DNA without modifications. Substitution of
      deoxyribonucleosides with a C3 or C4 alkyl-linker was found to be optimal for
      potentiating immunostimulatory activity.

PMID- 12238934
TI  - Salen-manganese complexes as catalytic scavengers of hydrogen peroxide and
      cytoprotective agents: structure-activity relationship studies.
AB  - Synthetic catalytic scavengers of reactive oxygen species (ROS) may have broad
      clinical applicability. In previous papers, two salen-manganese complexes, EUK-8
      and EUK-134, had superoxide dismutase (SOD) and catalase activities and prevented
      ROS-associated tissue injury. This study describes two series of salen-manganese
      complexes, comparing catalytic ROS scavenging properties and cytoprotective
      activities. The compounds vary widely in ability to scavenge hydrogen peroxide,
      with this activity most influenced by salen ring alkoxy substitution and aromatic
      bridge modifications. In contrast, all compounds show comparable SOD activities.
      The most active alkoxy-substituted catalase mimetics protected cultured cells
      from hydrogen peroxide, and a subset of these were also neuroprotective in a
      rodent stroke model. Thus, structural modification of the prototype EUK-8 yields
      compounds with enhanced catalase activity and, in turn, biological effectiveness.
      This supports the concept that salen-manganese complexes represent a class of SOD
      and, in particular, catalase mimetics potentially useful against ROS-associated
      diseases.

PMID- 12238935
TI  - 4-Substituted D-glutamic acid analogues: the first potent inhibitors of glutamate
      racemase (MurI) enzyme with antibacterial activity.
AB  - The first potent inhibitors of glutamate racemase (MurI) enzyme that show whole
      cell antibacterial activity are described. Optically pure 4-substituted D
      glutamic acid analogues with (2R,4S) stereochemistry and bearing aryl-,
      heteroaryl-, cinnamyl-, or biaryl-methyl substituents represent a novel class of
      glutamate racemase inhibitors. Exploration of the D-Glu core led to the
      identification of lead compounds (-)-8 and 10. 2-Naphthylmethyl derivative 10 was
      found to be a potent competitive inhibitor of glutamate racemase activity (K(i) =
      16 nM, circular dichroism assay; IC(50) = 0.1 microg/mL high-performance liquid
      chromatography (HPLC) assay). Thorough structure-activity relationship (SAR)
      studies led to benzothienyl derivatives such as 69 and 74 with increased potency
      (IC(50) = 0.036 and 0.01 microg/mL, respectively, HPLC assay). These compounds
      showed potent whole cell antibacterial activity against S. pneumoniae PN-R6, and
      good correlation with the enzyme assay. Compounds 69, 74 and biaryl derivative 52
      showed efficacy in an in vivo murine thigh infection model against Streptococcus
      pneumoniae. Data described herein suggest that glutamate racemase may be a viable
      target for developing new antibacterial agents.

PMID- 12238936
TI  - Synthesis of novel 4,1-benzoxazepine derivatives as squalene synthase inhibitors
      and their inhibition of cholesterol synthesis.
AB  - Modification of the carboxyl group at the 3-position and introduction of
      protective groups to the hydroxy group of the 4,1-benzoxazepine derivative 2
      (metabolite of 1) were carried out, and the inhibitory activity for squalene
      synthase and cholesterol synthesis in the liver was investigated. Among these
      compounds, the glycine derivative 3a and beta-alanine derivative 3f exhibited the
      most potent inhibition of squalene synthase prepared from HepG2 cells (IC(50) =
      15 nM). On the other hand, the piperidine-4-acetic acid derivative 4a, which was
      prepared by acetylation of 3j, was the most effective inhibitor of cholesterol
      synthesis in rat liver (ED(50) = 2.9 mg/kg, po). After oral administration, 4a
      was absorbed and rapidly hydrolyzed to deacylated 3j. Compound 3j was detected
      mainly in the liver, but the plasma level of 3j was found to be low. Compounds 3j
      and 4a were found to be competitive inhibitors with respect to farnesyl
      pyrophosphate. Further evaluation of 4a as a cholesterol-lowering and
      antiatherosclerotic agent is underway.

PMID- 12238937
TI  - Dicarboxylic acid bis(L-prolyl-pyrrolidine) amides as prolyl oligopeptidase
      inhibitors.
AB  - New dicarboxylic acid bis(L-prolyl-pyrrolidine) amides were synthesized, and
      their inhibitory activity against prolyl oligopeptidase from pig brain was tested
      in vitro. As compared with earlier described prolyl oligopeptidase inhibitors,
      these new compounds have in common an L-prolyl-pyrrolidine moiety, but the
      typical lipophilic acyl end group is replaced by another L-prolyl-pyrrolidine
      moiety connected symmetrically with a short dicarboxylic acid linker. These
      compounds are a new type of peptidomimetic prolyl oligopeptidase inhibitor.

PMID- 12238939
TI  - Exercise and the treatment of clinical depression in adults: recent findings and
      future directions.
AB  - This article critically reviews the evidence that exercise is effective in
      treating depression in adults. Depression is recognised as a mood state, clinical
      syndrome and psychiatric condition, and traditional methods for assessing
      depression (e.g. standard interviews, questionnaires) are described. In order to
      place exercise therapy into context, more established methods for treating
      clinical depression are discussed. Observational (e.g. cross-sectional and
      correlational) and interventional studies of exercise are reviewed in healthy
      adults, those with comorbid medical conditions, and patients with major
      depression. Potential mechanisms by which exercise may reduce depression are
      described, and directions for future research in the area are suggested. The
      available evidence provides considerable support for the value of exercise in
      reducing depressive symptoms in both healthy and clinical populations. However,
      many studies have significant methodological limitations. Thus, more data from
      carefully conducted clinical trials are needed before exercise can be recommended
      as an alternative to more traditional, empirically validated pharmacological and
      behavioural therapies.

PMID- 12238941
TI  - Alpine ski injuries and their prevention.
AB  - Alpine skiing is a popular sport with significant risk of injury. Since the
      1970s, injury rates have dropped from approximately 5 to 8 per 1000 skier-days to
      about 2 to 3 per 1000 skier-days. The nature of the injuries has also been
      transformed over the same period. Lower leg injuries are becoming less common
      while the incidence of knee sprains and upper extremity injuries is becoming more
      common. Much of this change can be attributed to advancements in binding
      technology, which effectively reduces lower leg injury, but does not adequately
      address the issue of knee sprains. Along with design, binding adjustment and
      maintenance are important preventative factors. Poorly adjusted bindings have
      been correlated with increased injury rates. Upper extremity injuries constitute
      approximately one-third of skiing injuries, with ulnar collateral ligament
      sprains and shoulder injuries being the most common. Strategies to prevent these
      include proper poling technique and avoidance of non-detachable ski pole
      retention devices. Spinal injuries in skiers have been traditionally much less
      common than in snowboarders, but this disparity is likely to diminish with the
      recent trend of incorporating snowboarding moves into skiing. Strategies to help
      reduce these injuries include promoting the development of terrain parks and
      focussing on proper technique during such moves. Head injuries have been
      increasing in incidence over recent decades and account for more than half of
      skiing-related deaths. The issue of ski helmets remains controversial while
      evidence for their efficacy remains under debate. There is no evidence to
      demonstrate that traditional ski instruction reduces injury frequency. More
      specific programmes focussed on injury prevention techniques are effective. The
      question of pre-season conditioning to prevent injuries needs further research to
      demonstrate efficacy.

PMID- 12238940
TI  - Factors affecting the rate of phosphocreatine resynthesis following intense
      exercise.
AB  - Within the skeletal muscle cell at the onset of muscular contraction,
      phosphocreatine (PCr) represents the most immediate reserve for the
      rephosphorylation of adenosine triphosphate (ATP). As a result, its concentration
      can be reduced to less than 30% of resting levels during intense exercise. As a
      fall in the level of PCr appears to adversely affect muscle contraction, and
      therefore power output in a subsequent bout, maximising the rate of PCr
      resynthesis during a brief recovery period will be of benefit to an athlete
      involved in activities which demand intermittent exercise. Although this
      resynthesis process simply involves the rephosphorylation of creatine by
      aerobically produced ATP (with the release of protons), it has both a fast and
      slow component, each proceeding at a rate that is controlled by different
      components of the creatine kinase equilibrium. The initial fast phase appears to
      proceed at a rate independent of muscle pH. Instead, its rate appears to be
      controlled by adenosine diphosphate (ADP) levels; either directly through its
      free cytosolic concentration, or indirectly, through its effect on the free
      energy of ATP hydrolysis. Once this fast phase of recovery is complete, there is
      a secondary slower phase that appears almost certainly rate-dependent on the
      return of the muscle cell to homeostatic intracellular pH. Given the importance
      of oxidative phosphorylation in this resynthesis process, those individuals with
      an elevated aerobic power should be able to resynthesise PCr at a more rapid rate
      than their sedentary counterparts. However, results from studies that have used
      phosphorus nuclear magnetic resonance ((31)P-NMR) spectroscopy, have been
      somewhat inconsistent with respect to the relationship between aerobic power and
      PCr recovery following intense exercise. Because of the methodological
      constraints that appear to have limited a number of these studies, further
      research in this area is warranted.

PMID- 12238943
TI  - Why has the use of health economic evaluation in Japan lagged behind that in
      other developed countries?
AB  - The aging population and the increasing availability of new medical technologies,
      particularly pharmaceuticals, have led to growing pressure on governments
      worldwide to contain healthcare costs. Increasingly, economic evaluation is used
      to aid decisions on the reimbursement and formulary access of drugs, and
      pharmaceutical companies are often required to demonstrate the cost effectiveness
      of their products. Canada and the UK are examples of countries that have
      successfully incorporated mandatory requirements for economic evaluations into
      the decision-making process in healthcare. Japan faces cost-containment issues
      for its health and welfare system similar to those seen elsewhere in the world.
      Despite this, economic assessments are not currently used in the allocation of
      drug budgets. Reasons why economic evaluations for healthcare have not yet been
      used routinely in Japan include governmental approaches to healthcare cost
      containment, the pricing of pharmaceuticals, the organisation of the healthcare
      system, attitudes of the medical profession, and limited knowledge and expertise.
      However, small but encouraging steps are now being taken towards the introduction
      of economic evaluations in Japanese medicine.

PMID- 12238942
TI  - Utility of pedometers for assessing physical activity: convergent validity.
AB  - Valid assessment of physical activity is important to researchers and
      practitioners interested in surveillance, screening, programme evaluation and
      intervention. The validity of an assessment instrument is commonly considered its
      most important attribute. Convergent validity is the extent to which an
      instrument's output is associated with that of other instruments intended to
      measure the same exposure of interest. A systematic review of the literature
      produced 25 articles directly relevant to the question of convergent validity of
      pedometers against accelerometers, observation, and self-reported measures of
      physical activity. Reported correlations were pooled and a median r-value was
      computed. Pedometers correlate strongly (median r = 0.86) with different
      accelerometers (specifically uniaxial accelerometers) depending on the specific
      instruments used, monitoring frame and conditions implemented, and the manner in
      which the outputs are expressed. Pedometers also correlate strongly (median r =
      0.82) with time in observed activity. Time in observed inactivity correlated
      negatively with pedometer outputs (median r = -0.44). The relationship with
      observed steps taken depended upon monitoring conditions and speed of walking.
      The highest agreement was apparent during ambulatory activity (running, walking)
      or during sitting (when both observation and pedometers would register few steps
      taken). There was consistent evidence of reduced accuracy during slow walking.
      Pedometers correlate moderately with different measures of energy expenditure
      (median r = 0.68). The relationship between pedometer outputs and energy
      expenditure is complicated by the use of many different direct and indirect
      measures of energy expenditure and population samples. Concordance with self
      reported physical activity (median r = 0.33) varied depending upon the self
      report instrument used, individuals assessed, and how pedometer outputs are
      expressed (e.g. steps, distance travelled, energy expenditure). Pedometer output
      has an inverse relationship with reported time spent sitting (r = -0.38). The
      accumulated evidence herein provides ample support that the simple and
      inexpensive pedometer is a valid option for assessing physical activity in
      research and practice.

PMID- 12238944
TI  - Information barriers to the implementation of economic evaluations in Japan.
AB  - With increasing cost-containment pressures within healthcare systems worldwide,
      economic evaluations of medical technologies, particularly pharmaceuticals, are
      used to aid the allocation of expenditure and resources. Facing similar
      pressures, Japan will probably also introduce economic evaluation of health
      technology. However, the structure of the healthcare system in Japan does not
      lend itself naturally to the collection of the epidemiological and cost data
      required for economic evaluations in medicine. In addition, there are no formal
      methodological guidelines in place for these analyses. To overcome these
      information barriers in Japan, progress may be aided by the adoption of
      approaches used in other countries for data collection and guideline development.

PMID- 12238945
TI  - The development and use of quality-of-life measures to evaluate health outcomes
      in Japan.
AB  - Health outcomes measurement forms a key aspect of data collection for economic
      evaluations. Quality-of-life instruments provide a measure of patient-focused
      health outcomes. Such instruments, including the EuroQoL questionnaire (EQ-5D)
      and the Short-form 36 (SF-36) are already being used in Japan. Utility
      instruments provide an alternative way of measuring quality of life for use in
      economic analyses. At present, utility measurement in Japan is limited to scores
      derived from the EQ-5D. Although the SF-36 was designed as a health profile
      measure, it has since been tested for use as a utility measure, with valuation of
      items now being undertaken in Japan. Utility measurement in Japan is likely to be
      advanced further by the validation and introduction of the Health Utilities
      Index. The experiences of other countries provide the opportunity for Japan to
      learn how utility scores may be used in cost-utility analyses of healthcare
      technologies.

PMID- 12238947
TI  - Comparative characterization of hexose transporters of Plasmodium knowlesi,
      Plasmodium yoelii and Toxoplasma gondii highlights functional differences within
      the apicomplexan family.
AB  - Chemotherapy of apicomplexan parasites is limited by emerging drug resistance or
      lack of novel targets. PfHT1, the Plasmodium falciparum hexose transporter 1, is
      a promising new drug target because asexual-stage malarial parasites depend
      wholly on glucose for energy. We have performed a comparative functional
      characterization of PfHT1 and hexose transporters of the simian malarial parasite
      P. knowlesi (PkHT1), the rodent parasite P. yoelii (PyHT1) and the human
      apicomplexan parasite Toxoplasma gondii ( T. gondii glucose transporter 1,
      TgGT1). PkHT1 and PyHT1 share >70% amino acid identity with PfHT1, while TgGT1 is
      more divergent (37.2% identity). All transporters mediate uptake of D-glucose and
      D-fructose. PyHT1 has an affinity for glucose ( K (m) approximately 0.12 mM) that
      is higher than that for PkHT1 ( K (m) approximately 0.67 mM) or PfHT1 ( K (m)
      approximately 1 mM). TgGT1 is highly temperature dependent (the Q (10) value, the
      fold change in activity for a 10 degrees C change in temperature, was >7)
      compared with Plasmodium transporters ( Q (10), 1.5-2.5), and overall has the
      highest affinity for glucose ( K (m) approximately 30 microM). Using active
      analogues in competition for glucose uptake, experiments show that hydroxyl
      groups at the C-3, C-4 and C-6 positions are important in interacting with PkHT1,
      PyHT1 and TgGT1. This study defines models useful to study the biology of
      apicomplexan hexose permeation pathways, as well as contributing to drug
      development.

PMID- 12238949
TI  - Significant quantities of the glycolytic enzyme phosphoglycerate mutase are
      present in the cell wall of yeast Saccharomyces cerevisiae.
AB  - NaOH was used to extract proteins from the cell walls of the yeast Saccharomyces
      cerevisiae. This treatment was shown not to disrupt yeast cells, as NaOH
      extracted cells displayed a normal morphology upon electron microscopy. Moreover,
      extracted and untreated cells had qualitatively similar protein contents upon
      disruption. When yeast was grown in the presence of 1 M mannitol, two proteins
      were found to be present at an elevated concentration in the cell wall. These
      were found to be the late-embryogenic-abundant-like protein heat-shock protein 12
      and the glycolytic enzyme phosphoglycerate mutase. The presence of
      phosphoglycerate mutase in the cell wall was confirmed by immunocytochemical
      analysis. Not only was the phosphoglycerate mutase in the yeast cell wall found
      to be active, but whole yeast cells were also able to convert 3-phosphoglycerate
      in the medium into ethanol, provided that the necessary cofactors were present.

PMID- 12238948
TI  - Copper-mediated dimerization of CopZ, a predicted copper chaperone from Bacillus
      subtilis.
AB  - Understanding the metal-binding properties and solution states of metallo
      chaperones is a key step in understanding how they function in metal ion
      transfer. Using spectroscopic, bioanalytical and biochemical methods, we have
      investigated the copper-binding properties and association states of the putative
      copper chaperone of Bacillus subtilis, CopZ, and a variant of the protein lacking
      the two cysteine residues of the MXCXXC copper-binding motif. We show that copper
      free CopZ exists as a monomer, but that addition of copper(I) causes the protein
      to associate into homodimers. The nature of the copper(I)-CopZ complex is
      dependent on the level of copper loading, and we report the detection of three
      distinct forms, containing 0.5, 1.0 and 1.5 copper(I) ions per protein. The
      presence of excess dithiothreitol has a significant effect on copper(I) binding
      to CopZ, such that, in its presence, copper(I)-CopZ occurs mainly as a monomer
      species. Data for copper binding to the double-cysteine variant of CopZ are
      consistent with an essential role for these residues in tight copper binding in
      the wild-type protein. We conclude that the complex nature of copper(I) binding
      to CopZ may underpin mechanisms of protein-to-protein copper(I) transfer.

PMID- 12238951
TI  - New enzyme belonging to the family of molybdenum-free nitrate reductases.
AB  - A novel molybdenum-free nitrate reductase was isolated from the obligate
      chemolithoautotrophic and facultative anaerobic, (halo)alkaliphilic sulphur
      oxidizing bacterium Thioalkalivibrio nitratireducens strain ALEN 2. The enzyme
      was found to contain vanadium and haem c as cofactors. Its native molecular mass
      was determined as 195 kDa, and the enzyme consists of four identical subunits
      with apparent molecular masses of 57 kDa. Apart from nitrate, the enzyme can
      utilize nitrite, chlorate, bromate, selenate and sulphite as electron acceptors.
      Moreover, it also has a haloperoxidase activity.

PMID- 12238950
TI  - Positive feedback of protein kinase C proteolytic activation during apoptosis.
AB  - In contrast with protein kinase Calpha (PKCalpha) and PKCepsilon, which are
      better known for promoting cell survival, PKCdelta is known for its pro-apoptotic
      function, which is exerted mainly through a caspase-3-dependent proteolytic
      activation pathway. In the present study, we used the rat GH3B6 pituitary adenoma
      cell line to show that PKCalpha and PKCepsilon are activated and relocalized
      together with PKCdelta when apoptosis is induced by a genotoxic stress.
      Proteolytic activation is a crucial step used by the three isoforms since: (1)
      the catalytic domains of the PKCalpha, PKCepsilon or PKCdelta isoforms (CDalpha,
      CDepsilon and CDdelta respectively) accumulated, and this accumulation was
      dependent on the activity of both calpain and caspase; and (2) transient
      expression of CDalpha, CDepsilon or CDdelta sufficed to induce apoptosis.
      However, following this initial step of proteolytic activation, the pathways
      diverge; cytochrome c release and caspase-3 activation are induced by CDepsilon
      and CDdelta, but not by CDalpha. Another interesting finding of the present study
      is the proteolysis of PKCdelta induced by CDepsilon expression that revealed the
      existence of a cross-talk between PKC isoforms during apoptosis. Hence the PKC
      family may participate in the apoptotic process of pituitary adenoma cells at two
      levels: downstream of caspase and calpain, and via retro-activation of caspase-3,
      resulting in the amplification of its own proteolytic activation.

PMID- 12238952
TI  - Workers' compensation claims related to natural rubber latex gloves among Oregon
      healthcare employees from 1987-1998.
AB  - BACKGROUND: Occupational reaction to natural rubber latex (NRL) glove use by
      healthcare employees has been an area of increasing concern. Unfortunately, there
      is little data demonstrating the prevalence and severity of actual reactivity to
      NRL. METHOD: Occupational reaction to NRL was estimated using workers'
      compensation claims filed by healthcare employees in Oregon for the period of
      1987-1998. For the first ten years, these claims were estimated by source and
      conditions consistent with NRL glove reactions, while in the last two years a
      specific code developed in 1997 for NRL glove reactions was also employed.
      RESULTS: The claim rate was on average 0.58 per 10,000 healthcare workers
      annually, which constituted 0.29% of all workers' compensation claims. The most
      common condition experienced was dermatitis (80%) and most common body part
      affected was the hands (55.4%). The majority of claimants, 45 (69.2%), reported
      taking less than a month off work, suggesting most reactions were minor in
      nature, although one fatality was reported. The average NRL claim cost was
      $8,309.48. Overall the average cost per insured healthcare worker was
      approximately $0.50 per year. The occupational groups with the highest number of
      claims were nurses (30.8% of claimants) and nursing aides and orderlies (24.6% of
      claimants). CONCLUSIONS: In comparison with other workers' compensation claims
      filed by healthcare workers during this period, 0.25% of the total was
      potentially related to NRL gloves. The rare incidence of respiratory and ocular
      claims is inconsistent with the hypothesis that asthmatic or conjunctival
      reactions to NRL gloves are common.

PMID- 12238953
TI  - Expression of human beta-defensins 1 and 2 in kidneys with chronic bacterial
      infection.
AB  - BACKGROUND: Constitutive expression and localization of antimicrobial human beta
      defensin-1 (HBD-1) in human kidneys as a potential mechanism of antimicrobial
      defense has been previously reported. Inducible expression of human beta-defensin
      2 (HBD-2) has been described in various epithelial organs but not for the
      urogenital tract. METHODS: We investigated the gene- and protein expression of
      HBD-1 and HBD-2 by reverse transcriptase-polymerase chain reaction, and
      immunohistochemistry in 15 normal human kidney samples and 15 renal tissues with
      chronic bacterial infection. Additionally, cell culture experiments were
      performed to study HBD gene expression by real-time RT-PCR in response to
      inflammatory cytokines TNFalpha and IL-1beta as well as lipopolysaccharide from
      Gram-negative bacteria. RESULTS: Constitutive HBD-1 gene- and protein expression
      was detected in normal renal tissue and kidneys with chronic infection. As a
      novel finding, inducible HBD-2 gene- and protein expression was demonstrated in
      tubulus epithelia with chronic infection but not in normal renal tissue. In
      pyelonephritic kidneys HBD-1 and HBD-2 expression showed a similar pattern of
      localization in distal tubules, loops of Henle and in collecting ducts of the
      kidney. Furthermore, real-time RT-PCR of kidney derived cell lines stimulated
      with inflammatory agents TNF-alpha, IL-1beta and LPS revealed a strong increase
      in relative HBD-2 transcription level and also a slight increase in relative HBD
      1 transcription level. CONCLUSIONS: Upregulated HBD-2 expression in renal tubulus
      epithelium indicates a role of a wider range of human defensins for antimicrobial
      host defense in the urogenital tract than previously recognized.

PMID- 12238954
TI  - Statistical issues in randomized trials of cancer screening.
AB  - BACKGROUND: The evaluation of randomized trials for cancer screening involves
      special statistical considerations not found in therapeutic trials. Although some
      of these issues have been discussed previously, we present important recent and
      new methodologies. METHODS: Our emphasis is on simple approaches. RESULTS: We
      make the following recommendations: (1) Use death from cancer as the primary
      endpoint, but review death records carefully and report all causes of death; (2)
      Use a simple "causal" estimate to adjust for nonattendance and contamination
      occurring immediately after randomization; (3) Use a simple adaptive estimate to
      adjust for dilution in follow-up after the last screen CONCLUSION: The proposed
      guidelines combine recent methodological work on screening endpoints and
      noncompliance/contamination with a new adaptive method to adjust for dilution in
      a study where follow-up continues after the last screen. These guidelines ensure
      good practice in the design and analysis of randomized trials of cancer
      screening.

PMID- 12238994
TI  - Author, author!

PMID- 12238995
TI  - Histologic evaluation of the shoulder capsule in normal shoulders, unstable
      shoulders, and after failed thermal capsulorrhaphy.
AB  - BACKGROUND: Attenuation of the shoulder capsule has been noted during revision
      surgery for failed thermal capsulorrhaphy. HYPOTHESIS: The attenuated capsule
      seen in patients who have undergone failed thermal capsulorrhaphy will show
      histologic characteristics distinguishing it from the capsule of normal shoulders
      and dislocating shoulders. STUDY DESIGN: Case control study. METHODS: The
      shoulder capsules were studied in 12 patients with traumatic anterior instability
      and in 7 patients who experienced recurrent instability after a thermal
      capsulorrhaphy. The capsules of six fresh-frozen cadavers with no shoulder
      lesions were used as controls. RESULTS: Among patients who had a history of
      traumatic instability, a denuded synovial layer was present in 58%, subsynovial
      edema in 58%, increased cellularity in 25%, and increased vascularity in 83%. At
      the time of surgery, five of seven shoulders in the failed thermal capsulorrhaphy
      group (71%) were subjectively felt to be thin and attenuated. Denuded synovium
      was found in 100% of these patients, subsynovial edema in 43%, and changes in the
      collagen layer in 100%. Changes in the collagen layer in these patients included
      a "hyalinization" appearance in five cases (71%), increased collagen fibrosis in
      two cases (29%), and increased cellularity in two cases (29%). CONCLUSIONS: There
      was no one characteristic observable on histologic evaluation that would explain
      the attenuation of the capsule in cases of failed thermal treatment. Morphologic
      collagen structure can be histologically abnormal for up to 16 months after
      thermal capsulorrhaphy.

PMID- 12238996
TI  - Posterior cruciate ligament femoral insertion site characteristics. Importance
      for reconstructive procedures.
AB  - BACKGROUND: Previous descriptions of the insertion site of the posterior cruciate
      ligament are inadequate. HYPOTHESIS: More than one reference system is required
      to adequately represent the anatomy of the femoral attachment. STUDY DESIGN:
      Descriptive anatomic study. METHODS: Twelve cadaveric specimens were evaluated by
      using two measurement methods relative to the femoral articular cartilage margin
      and two methods relative to the intercondylar femoral roof. RESULTS: Reference
      lines perpendicular to the articular cartilage best defined the 12- and 1-o'clock
      positions, and those perpendicular to the articular cartilage or parallel to the
      femoral shaft best defined the 2-, 3-, and 4-o'clock positions. The angle of the
      proximal attachment to the roof was 88 degrees +/- 5.5 degrees. The posterior
      cruciate ligament was a continuum of fibers rather than two distinct bundles, and
      its attachment showed variability in shape and thickness, extending past the
      midline in the notch (11:21 +/- 15 minutes to 4:12 +/- 20 minutes, right knee).
      CONCLUSIONS: More than one measurement system is required to accurately describe
      the femoral origin of the posterior cruciate ligament. CLINICAL RELEVANCE:
      Accurate assessment of the anatomy is crucial for successful surgical
      reconstruction of the posterior cruciate ligament femoral attachment.

PMID- 12238997
TI  - Prevention of soccer injuries: a prospective intervention study in youth amateur
      players.
AB  - BACKGROUND: Risk factors for soccer injuries and possibilities for prevention
      have been discussed by several authors, but only a few have investigated the
      effectiveness of preventive interventions. PURPOSE: The aim of the present study
      was to evaluate the effects of a prevention program on the incidence of soccer
      injuries in male youth amateur players. STUDY DESIGN: Prospective controlled
      intervention study. METHODS: Seven soccer teams took part in a prevention program
      that focused on education and supervision of coaches and players, while seven
      other teams were instructed to train and play soccer as usual. Over 1 year all
      injuries were documented weekly by physicians. Complete weekly injury reports
      were available for 194 players. RESULTS: The incidence of injury per 1000 hours
      of training and playing soccer was 6.7 in the intervention group and 8.5 in the
      control group, which equates to 21% fewer injuries in the intervention group. The
      greatest effects were observed for mild injuries, overuse injuries, and injuries
      incurred during training. The prevention program had greater effects in low-skill
      than in high-skill teams. CONCLUSIONS: The incidence of soccer injuries can be
      reduced by preventive interventions, especially in low skill level youth teams.
      Coaches and players need better education regarding injury prevention strategies
      and should include such interventions as part of their regular training.

PMID- 12238999
TI  - Lavage solution temperature influences depth of chondrocyte death and surface
      contouring during thermal chondroplasty with temperature-controlled monopolar
      radiofrequency energy.
AB  - BACKGROUND: Although radiofrequency energy can smooth and contour cartilage
      surface, it has deleterious effects on chondrocyte viability. HYPOTHESIS:
      Monopolar thermal chondroplasty in a 37 degrees C lavage solution, as compared
      with a 22 degrees lavage solution, will reduce chondrocyte death and result in
      greater smoothing of the articular cartilage surface. STUDY DESIGN: Controlled
      laboratory study. METHODS: Sixteen chondromalacic samples from patients
      undergoing total knee arthroplasty were divided into two groups: 22 degrees C and
      37 degrees C lavage solution. Each sample was divided into two equal parts and
      half of each group was treated for 10 seconds and the other half for 15 seconds.
      RESULTS: Confocal laser microscopy demonstrated that the depth of chondrocyte
      death in the 37 degrees C lavage solution group was significantly less (range,
      200 to 340 microm) than that in the 22 degrees C solution group for both 10- and
      15-second treatment times. Scanning electron microscopy demonstrated that the
      cartilage surface in the 37 degrees C lavage solution group was smoother than
      that in the 22 degrees C solution group for the 10-second treatment time. Energy
      delivery power in the 37 degrees C lavage solution group was significantly lower
      than in the 22 degrees C solution group for both treatment times. CONCLUSIONS:
      Thermal chondroplasty with 37 degrees C lavage solution resulted in less depth of
      chondrocyte death and produced smoother surfaces than with 22 degrees C solution
      for 10 seconds of treatment. CLINICAL RELEVANCE: Less chondrocyte death would
      permit increased use of thermal chondroplasty.

PMID- 12238998
TI  - Biomechanical analysis of an anatomic anterior cruciate ligament reconstruction.
AB  - BACKGROUND: The focus of most anterior cruciate ligament reconstructions has been
      on replacing the anteromedial bundle and not the posterolateral bundle.
      HYPOTHESIS: Anatomic two-bundle reconstruction restores knee kinematics more
      closely to normal than does single-bundle reconstruction. STUDY DESIGN:
      Controlled laboratory study. METHODS: Ten cadaveric knees were subjected to
      external loading conditions: 1) a 134-N anterior tibial load and 2) a combined
      rotatory load of 5-N x m internal tibial torque and 10-N x m valgus torque.
      Resulting knee kinematics and in situ force in the anterior cruciate ligament or
      replacement graft were determined by using a robotic/universal force-moment
      sensor testing system for 1) intact, 2) anterior cruciate ligament deficient, 3)
      single-bundle reconstructed, and 4) anatomically reconstructed knees. RESULTS:
      Anterior tibial translation for the anatomic reconstruction was significantly
      closer to that of the intact knee than was the single-bundle reconstruction. The
      in situ force normalized to the intact anterior cruciate ligament for the
      anatomic reconstruction was 97% +/- 9%, whereas the single-bundle reconstruction
      was only 89% +/- 13%. With a combined rotatory load, the normalized in situ force
      for the single-bundle and anatomic reconstructions at 30 degrees of flexion was
      66% +/- 40%and 91% +/- 35%, respectively. CONCLUSIONS: Anatomic reconstruction
      may produce a better biomechanical outcome, especially during rotatory loads.
      CLINICAL RELEVANCE: Results may lead to the use of a two-bundle technique.

PMID- 12239000
TI  - Back pain in intercollegiate rowers.
AB  - BACKGROUND: Back pain is prevalent among intercollegiate rowers. PURPOSE: We
      conducted a large-scale study to determine the rate of and the potential
      etiologic factors for clearly defined back pain that developed during
      intercollegiate rowing. STUDY DESIGN: Survey. METHODS: Surveys from 1632 former
      intercollegiate rowing athletes were analyzed. These surveys concerned training
      methods and back pain before and during intercollegiate rowing. Back pain was
      defined as pain that lasted at least 1 week. RESULTS: Five hundred twenty-six
      subjects reported that back pain developed during intercollegiate rowing. Factors
      significantly associated with the development of back pain included age at the
      time of the survey; history of rowing before age 16; use of a hatchet oar blade;
      training with free weights, weight machines, and an ergometer; midline ergometer
      cable position; and ergometer training sessions longer than 30 minutes. Back pain
      while in college also was associated with higher mean college weight and height.
      CONCLUSIONS: Intercollegiate rowers in the last 10 years covered by this study
      were larger, started rowing at an earlier age, trained more intensely, and
      developed more back pain during college than their predecessors.

PMID- 12239001
TI  - The effectiveness of a preseason exercise program to prevent adductor muscle
      strains in professional ice hockey players.
AB  - BACKGROUND: Adductor strains are among the most common injuries in ice hockey.
      Hip adductor weakness has been identified as a strong risk factor. HYPOTHESIS: An
      intervention program including muscle strengthening can reduce the incidence of
      adductor strains in professional ice hockey players. STUDY DESIGN: Prospective
      risk factor prevention study. METHODS: Thirty-three of 58 players from the same
      National Hockey League team were identified as "at risk" on the basis of
      preseason hip adductor strength and participated in an intervention program. The
      program consisted of 6 weeks of exercises aimed at functional strengthening of
      the adductor muscles. Injury and individual exposure data were recorded for all
      players. RESULTS: There were 3 adductor strains in the 2 seasons subsequent to
      the intervention, compared with 11 in the previous 2 seasons (0.71 versus 3.2 per
      1000 player-game exposures). All adductor strains were first-degree strains and
      occurred during games. CONCLUSIONS: A therapeutic intervention of strengthening
      the adductor muscle group appears to be an effective method for preventing
      adductor strains in professional ice hockey players.

PMID- 12239002
TI  - Braided hamstring tendons for reconstruction of the anterior cruciate ligament. A
      biomechanical analysis.
AB  - BACKGROUND: In an effort to improve the strength and stiffness of anterior
      cruciate ligament grafts, several authors have advocated alterations of graft
      structure and orientation, including braiding the tendons in hamstring tendon
      grafts. HYPOTHESIS: Braiding hamstring tendons does not increase graft strength
      and stiffness. STUDY DESIGN: Controlled laboratory study. METHODS: Sixteen
      hamstring tendon and 21 bone-patellar tendon-bone grafts were harvested from 12
      cadavers and divided into three groups: 1) braided four-strand hamstring tendon,
      2) unbraided four-strand hamstring tendon, and 3) bone-patellar tendon-bone. All
      grafts were placed under a 50-N preload on a servohydraulic testing device and
      were tensioned to failure. RESULTS: The strength and stiffness of the tested
      specimens averaged 427 +/- 36 N and 76 +/- 10 N/mm, respectively, for braided
      specimens, 532 +/- 44 N and 139 +/- 18 N/mm for unbraided specimens, and 574 +/-
      46 N and 158 +/- 15 N/mm for patellar tendon specimens. There was a 20% decrement
      in hamstring tendon graft tensile strength and a 45% decrease in stiffness after
      braiding because of the suboptimal multidirectional orientation of individual
      tendons within the braided grafts. CONCLUSIONS: In vitro braided hamstring tendon
      grafts demonstrated mechanically inferior strength and stiffness characteristics
      compared with unbraided hamstring tendon grafts and patellar tendon grafts.
      CLINICAL RELEVANCE: Braiding of hamstring tendon grafts provides no mechanical
      advantage in anterior cruciate ligament reconstruction.

PMID- 12239003
TI  - Long-term prognosis for jumper's knee in male athletes. A prospective follow-up
      study.
AB  - BACKGROUND: Little information is available on the long-term outcome of jumper's
      knee, a common problem among athletes. PURPOSE: Our aim was to determine the 15
      year prognosis of jumper's knee. STUDY DESIGN: Prospective case control. METHODS:
      The prognosis for jumper's knee was studied using two groups: athletes with
      jumper's knee and nonsymptomatic control athletes. At baseline, all subjects
      participated in standardized clinical examinations and measurements, and 15 years
      later they were asked to respond to a questionnaire. RESULTS: Twenty athletes
      with jumper's knee and 16 athlete control subjects responded (response rate 74%
      and 84%, respectively). The jumper's knee group reported significantly more knee
      symptoms according to their Kujala score and more knee pain after repeated
      squatting. Fifty-three percent of the subjects in the jumper's knee group (9 of
      17) reported that they had quit their sports career because of their knee
      problem, compared with 7% of the control athletes (1 of 14). Patellar height was
      associated with knee symptoms at follow-up. CONCLUSION: Jumper's knee causes mild
      but long-lasting symptoms after an athletic career.

PMID- 12239004
TI  - The 7-o'clock posteroinferior portal for shoulder arthroscopy.
AB  - BACKGROUND: Access to the inferior glenohumeral joint of the shoulder is very
      limited through the traditional 2- or 3-o'clock anterior portals. HYPOTHESIS: The
      7-o'clock posteroinferior portal offers an excellent alternative approach. STUDY
      DESIGN: Descriptive anatomic study. METHODS: Six paired cadaveric shoulders were
      used to arthroscopically develop and test a 7-o'clock posteroinferior portal. The
      distances between the portal and the subscapular and axillary nerves were
      measured with the arm in six different positions, combining flexion, extension,
      abduction, and adduction. RESULTS: The distance from the 7-o'clock
      posteroinferior portal to the axillary nerve was 39 +/- 4 mm and to the
      suprascapular nerve was 28 +/- 2 mm. There was no statistically significant nerve
      to-portal differential distance when the arm was placed in flexion, extension,
      abduction, or adduction. The inside-to-outside technique produced a 7-o'clock
      posteroinferior portal approximately 5 mm further from both the axillary and
      suprascapular nerves than did the outside-to-inside method. The angle of
      divergence from the 7-o'clock posterior portal skin incision to the axillary
      nerve was 47 degrees and to the suprascapular nerve was 33 degrees. CONCLUSIONS:
      The 7-o'clock portal affords safe, direct working access to the inferior capsular
      recess of the glenohumeral joint. CLINICAL RELEVANCE: The 7-o'clock portal is a
      safe and effective technique for use by shoulder surgeons.

PMID- 12239005
TI  - Partial tears of the anterior cruciate ligament in children and adolescents.
AB  - BACKGROUND: The functional outcome after partial anterior cruciate ligament tears
      in children and adolescents treated without reconstruction has not been
      established. HYPOTHESIS: Nonreconstructive management of partial anterior
      cruciate ligament tears can be effective in certain pediatric patients. STUDY
      DESIGN: Prospective cohort study. METHODS: We studied 45 skeletally mature and
      immature patients 17 years of age or less who had an acute hemarthrosis, magnetic
      resonance imaging signal changes, grade A or B Lachman and pivot shift result,
      and an arthroscopically documented partial anterior cruciate ligament tears. All
      patients were treated without reconstruction, underwent a structured
      rehabilitation program, and were followed up for a minimum of 2 years. RESULTS:
      Fourteen patients (31%) underwent subsequent reconstruction. Significant
      associations with subsequent reconstruction included tears that were greater than
      50%, predominantly posterolateral tears, a grade B pivot shift test result, and
      older chronologic and skeletal age. Among patients who did not require
      reconstruction, those with tears that were greater than 50% or predominantly
      posterolateral had significantly lower Lysholm, satisfaction, and Cincinnati Knee
      Scale scores. CONCLUSIONS: Nonreconstructive management is recommended for
      partial anterior cruciate ligament tears in children and adolescents 14 years of
      skeletal age or younger with normal or near-normal Lachman and pivot shift
      results. Reconstruction is recommended in older athletes or in those with greater
      than 50% or predominantly posterolateral tears.

PMID- 12239006
TI  - Comparison of two procedures for meniscal cysts. A report of 35 patients with a
      mean follow-up of 33 months.
AB  - BACKGROUND: The cause, pathogenesis, and appropriate treatment of meniscal cysts
      remain controversial. PURPOSE: We wanted to evaluate the results of treatment of
      meniscal cysts with two different operative procedures. STUDY DESIGN: Prospective
      cohort study. METHODS: Two different operative procedures were compared. Sixteen
      patients (group 1) had an open excision of the cyst performed in addition to
      arthroscopic examination of the knee. Nineteen patients (group 2) were treated
      entirely arthroscopically. The postoperative treatment course was the same for
      both groups. The mean length of follow-up was 33 months. RESULTS: The results
      were excellent or good in 86% of the patients (30 of 35) and were equally good
      for both procedures. Patients with degenerative changes of the knee joint seemed
      to have a less favorable outcome. CONCLUSIONS: Good or excellent results can be
      expected from either open or arthroscopic treatment of meniscal cysts.

PMID- 12239007
TI  - Effort thrombosis in the elite throwing athlete.
AB  - BACKGROUND: Upper extremity vascular injuries are uncommon in the elite throwing
      athlete. However, the extreme stresses that are placed on the upper extremity of
      elite baseball players, especially pitchers, puts them at risk for such injuries.
      One such injury is upper extremity venous thrombosis or "effort thrombosis."
      PURPOSE: We wanted to review the common initial clinical symptoms and physical
      examination findings of effort thrombosis in elite baseball players and to review
      the associated clinical conditions such as hypercoagulable states and pulmonary
      embolism. STUDY DESIGN: Retrospective review of a series of cases. METHODS: A
      retrospective review of the medical records of a Major League Baseball
      organization and a Division I college was performed for the period 1987 to 1997.
      RESULTS: We located four cases of effort thrombosis involving elite baseball
      players. Contrast venography was used to confirm the diagnosis in all cases. All
      patients were successfully treated with transluminal catheter-directed urokinase
      thrombolysis followed by first rib resection and systemic anticoagulant therapy
      for up to 3 months. All four players returned to play at or above their previous
      level of competition with no long-term chronic sequelae. CONCLUSIONS: Prompt
      clinical recognition, diagnosis, and treatment of effort thrombosis in the elite
      baseball player provides the player with an excellent prognosis for return to the
      previous level of play.

PMID- 12239008
TI  - A surgical treatment for unstable osteochondritis dissecans lesions of the
      humeral capitellum in adolescent baseball players.
AB  - BACKGROUND: Various methods of surgical treatment for unstable osteochondritis
      dissecans lesions of the humeral capitellum have shown the potential to lead to
      osteoarthritis and poor functional results in throwing activities. PURPOSE: The
      purpose of this study was to evaluate the results of surgical treatment with pull
      out wiring and bone grafting (as established by Kondo in 1989) in patients with
      unstable osteochondritis dissecans lesions of the humeral capitellum. STUDY
      DESIGN: Retrospective review. METHODS: Eleven male baseball players (average age,
      14.7 years) with unstable osteochondritis dissecans lesions underwent internal
      fixation with pull-out wiring and bone grafting. Follow-up was an average 57
      months. At an average 17 weeks after surgery, bony union of the osteochondritis
      dissecans lesion was radiographically confirmed and the wires were removed.
      Throwing was allowed beginning at 6 months after surgery. RESULTS: At follow-up,
      all patients had obtained pain relief, and all except one had returned to
      previous throwing levels. Radiographs showed good healing, and minimal
      degenerative changes were found in only three joints. CONCLUSION: Healing of
      osteochondritis dissecans lesions of the elbow can be achieved after fragment
      fixation with pull-out wiring and a bone grafting technique.

PMID- 12239009
TI  - Comparison of surgical repair or reconstruction of the cruciate ligaments versus
      nonsurgical treatment in patients with traumatic knee dislocations.
AB  - BACKGROUND: Studies of traumatic knee dislocations have failed to provide a
      consensus regarding the best method of treatment. PURPOSE: Our purpose was to
      evaluate the results after surgical repair or reconstruction versus nonsurgical
      treatment and to compare the influence of prognostic factors. STUDY DESIGN:
      Retrospective study. METHODS: Eighty-nine patients were treated for traumatic
      knee dislocation. Surgical repair or reconstruction of the cruciate ligaments was
      performed in 63 patients (repair, 49; reconstruction, 14). In 26 patients,
      nonsurgical treatment was undertaken. RESULTS: At an average follow-up of 8.2
      years, the mean Lysholm and Tegner scores were 75 and 3.7, respectively. The
      outcome in the surgical group was better than in the nonsurgical group. The
      scores were higher in patients who were 40 years of age or younger, who had
      sports injuries rather than motor vehicle accident injuries, and who had
      undergone functional rehabilitation rather than immobilization. CONCLUSIONS:
      Surgical repair or reconstruction of the cruciate ligaments was superior to
      nonsurgical treatment. Functional rehabilitation was the most important positive
      prognostic factor. Surgical repair or reconstruction of the cruciate ligaments is
      mandatory to achieve sufficient stability for functional rehabilitation. In cases
      of cruciate ligament avulsion, repair with transosseous fixation is a reasonable
      alternative to reconstruction, provided that it is performed within 2 weeks of
      trauma.

PMID- 12239011
TI  - Stress injury of the proximal ulna in professional baseball players.
AB  - BACKGROUND: To date, stress injury of the proximal ulna has been infrequently
      reported as a cause of elbow pain in the throwing athlete. PURPOSE: We describe a
      syndrome of osseous stress injury of the proximal ulna in the professional
      throwing athlete. STUDY DESIGN: Retrospective review. METHODS: We evaluated the
      clinical, radiographic, and magnetic resonance imaging findings of seven
      professional baseball players with osseous stress injury of the proximal ulna.
      RESULTS: Plain radiographs of the involved elbows failed to demonstrate any
      significant findings. All of the clinically significant lesions were detected
      with magnetic resonance imaging. In addition, magnetic resonance imaging was
      found to be of value in following the course of healing of the injuries. All of
      the lesions originated on the posteromedial aspect of the proximal ulna. The
      ulnar collateral ligament was intact in all seven athletes. One athlete had two
      occurrences of this injury. Six of the seven athletes returned to their previous
      level of play after a nonoperative course of treatment. CONCLUSIONS: We believe
      that this injury should be considered in the differential diagnosis of elbow pain
      in the throwing athlete. Magnetic resonance imaging is the diagnostic test of
      choice when this injury is suspected.

PMID- 12239010
TI  - Arthroscopic removal of symptomatic Bennett lesions in the shoulders of baseball
      players: arthroscopic Bennett-plasty.
AB  - BACKGROUND: Bennett lesions are often observed in throwing athletes, and,
      although usually asymptomatic, they can sometimes become painful and disturb an
      athlete's throwing ability. Because it is clinically difficult to determine
      whether a Bennett lesion is symptomatic or whether pain is from another lesion,
      the outcome of surgical treatment is variable. HYPOTHESIS: Arthroscopic resection
      of Bennett lesions diagnosed according to our criteria and arthroscopic treatment
      of associated lesions performed simultaneously were effective for treatment of
      baseball players with symptomatic Bennett lesions. STUDY DESIGN: Prospective
      cohort study. METHODS: The following criteria for diagnosis of a symptomatic
      Bennett lesion were used to identify 16 baseball players who later underwent
      arthroscopic removal of the symptomatic Bennett lesion (arthroscopic Bennett
      plasty): 1) detection of a bony spur at the posterior glenoid rim on radiographs;
      2) posterior shoulder pain during throwing, especially in the follow-through
      phase; 3) tenderness at the posteroinferior aspect of the glenohumeral joint; and
      4) relief of pain by injection of local anesthesia. RESULTS: After a minimum
      follow-up of 1 year, there was no tenderness at the posteroinferior aspect of the
      glenohumeral joint in any of the patients. Throwing pain disappeared in 10
      shoulders and was mitigated in 6 shoulders. Eleven patients returned to baseball
      at their previous level of competition. CONCLUSIONS: Accurate diagnosis and
      minimally invasive arthroscopic surgery are important for appropriate treatment
      of baseball players with symptomatic Bennett lesions.

PMID- 12239012
TI  - Surgical repair of complete proximal hamstring tendon rupture.
AB  - BACKGROUND: Complete proximal hamstring tendon rupture is a rare injury
      associated with significant functional loss. Nonoperative treatment has proven
      inadequate in returning patients to their previous activity level. PURPOSE: We
      wanted to describe the outcome of primary surgical repair of the proximal
      hamstring tendon avulsion. STUDY DESIGN: Retrospective cohort study. METHODS:
      Between 1994 and 1999, 11 patients (4 women and 7 men) with an average age of
      41.5 years (range, 21 to 51) had a diagnosis of complete proximal hamstring
      tendon rupture based on mechanism of injury, physical examination, and
      radiographic assessment. All underwent a single operation followed by standard
      postoperative physical therapy. At the latest follow-up (average, 34 months),
      patients completed a questionnaire regarding such outcome parameters as pain,
      function, leg control, stiffness, return to activity, and overall satisfaction.
      RESULTS: Isokinetic muscle testing revealed an overall average of 91%return of
      hamstring muscle strength. Ten of 11 patients were satisfied with the result, and
      7 of 9 athletically active patients were able to return to sport an average of 6
      months (range, 3 to 10) after surgery. No difference between early and late
      repairs was identified in regard to functional outcome or return to sport.
      CONCLUSIONS: Satisfactory results can be achieved with both early and late
      hamstring tendon repairs in a majority of cases with surgical repair.

PMID- 12239013
TI  - Avulsion of the middle genicular artery: a previously unreported complication of
      anterior cruciate ligament repair. A case report.

PMID- 12239014
TI  - Spontaneous healing of a patellar tendon anterior cruciate ligament graft. A case
      report.

PMID- 12239015
TI  - Acute nonexertional lateral compartment syndrome from snowboarding. A case
      report.

PMID- 12239016
TI  - The unstable shoulder in the adolescent athlete.
AB  - Shoulder dislocation and subluxation occur frequently in athletes, with peaks in
      the second and sixth decades. The majority of traumatic dislocations are in the
      anterior direction. The most frequent complication of shoulder dislocation is
      recurrence--a complication that occurs much more often in the adolescent
      population. The dynamic (muscular) and static (predominantly capsuloligamentous
      and labral) restraints to shoulder instability are now well defined. Recent
      surgical procedures for shoulder instability have become less interventional and
      have focused on restoring disrupted static restraints. The aim of rehabilitation
      is to enhance the dynamic muscular and proprioceptive restraints to shoulder
      instability.

PMID- 12239017
TI  - Whole-body CT screening: edging toward commerce.

PMID- 12239019
TI  - Screening for preclinical disease: test and disease characteristics.

PMID- 12239020
TI  - CT screening for lung cancer.

PMID- 12239021
TI  - Liability of performing CT screening for coronary artery disease and lung cancer.

PMID- 12239022
TI  - Physician self-referral for diagnostic imaging: review of the empiric literature.

PMID- 12239023
TI  - Updated findings from a help wanted index of job advertisements and an analysis
      of the policy implications: is the job-market shortage for diagnostic
      radiologists stabilizing?
AB  - OBJECTIVE: The goal of our study is to present the most recent data on the
      diagnostic radiology job market in the United States using a help wanted index of
      job advertisements. MATERIALS AND METHODS: All diagnostic radiology jobs
      advertised in the American Journal of Roentgenology and Radiology between January
      2000 and December 2001 were coded by practice type, geographic location, and
      subspecialty and were compared with the previously published results from 1991
      through 1999. RESULTS: From January 1999 through December 2001, 15,205 positions
      were advertised for diagnostic radiologists, representing a 284% average per
      month increase as compared with the previous 4-year period. The 12-month rolling
      average of job advertisements peaked in June 2001 at 476 and has since
      stabilized. Thirty-six percent of positions advertised were academic, identical
      to the proportion found from 1995 to 1998. A statistically significant relative
      increase in jobs advertised was noted in the Midwest, and relative decreases were
      seen in the Northeast, Northwest, Southwest, and (most recently) California.
      Statistically significant relative decreases were also observed in the number of
      general radiology, vascular and interventional, and emergency radiology
      positions. The demand for mammographers, pediatric radiologists,
      neuroradiologists, abdominal imagers, and chest radiologists all exhibited
      statistically significant relative increases. CONCLUSION: The absolute demand for
      both private and academic radiologists continued to grow throughout the country
      and in all subspecialties, but the pace of increase has slowed dramatically
      during the past 12 months, especially in the western United States. Current
      policy should be directed toward training for the areas of greatest need.

PMID- 12239024
TI  - Dedicated CT scanner in an emergency department: quantification of factors that
      contribute to lack of use.
AB  - OBJECTIVE: The purpose of our study was to quantify the factors that contribute
      to the lack of use of a dedicated CT scanner in the emergency department of our
      institution and to identify possible changes to reduce scanner idle time.
      MATERIALS AND METHODS: We designed a data collection form to record consecutive
      periods of patient scanning and periods between patients when the CT scanner was
      not in use. The contributing factors for each idle period were identified and
      logged according to an entry system previously decided in consensus. Data were
      collected continuously for 11 days. The factors we identified for measurement
      were no request for scanning, preventive maintenance, equipment failure,
      technologist unavailable, room cleaning and preparation, patient preparation for
      abdominal CT, patient undergoing other tests, transportation delays, pending
      laboratory workup, and miscellaneous factors. The time attributed to the most
      prevalent factors was also grouped into four 6-hr periods corresponding to our
      department's shifts. RESULTS: The scanner was idle 73% of the total study time.
      The chief contributing factors to lack of use were having no patients to scan,
      patient undergoing preparation, and transportation delays, which accounted for
      38.5%, 31%, and 11.7% of the aggregate idle time, respectively. The 6-hr periods
      of least use were the 7:00 A.M.-1:00 P.M. and the 1:00 A.M.-7:00 A.M. shifts,
      which accounted for 17% and 19% of idle time, respectively. CONCLUSION: Dedicated
      emergency department CT scanners can have significant daily periods of consistent
      lack of use. The idle time can be reduced by identifying patterns of referral
      time and correcting specific operational delays.

PMID- 12239025
TI  - Magnetization transfer contrast in rapid three-dimensional MR imaging using
      segmented radiofrequency prepulses.

PMID- 12239026
TI  - Whole-body turbo short tau inversion recovery MR imaging using a moving tabletop.

PMID- 12239027
TI  - Predicting the presence of acute pulmonary embolism: a comparative analysis of
      the artificial neural network, logistic regression, and threshold models.
AB  - OBJECTIVE: The objective of this study was to determine whether an artificial
      neural network, a new data analysis method, offers increased performance over
      conventional logistic regression in predicting the presence of a pulmonary
      embolism for patients in a well-known data set. MATERIALS AND METHODS: Data from
      the 1064 patients who received an angiographically based diagnosis of pulmonary
      embolism in the Prospective Investigation of Pulmonary Embolism Diagnosis study
      were encoded using a previously described method. The 21 input variables
      represented abnormalities identified on each patient's ventilation-perfusion scan
      and chest radiograph. Two methods-an artificial neural network with one hidden
      layer and a multivariate logistic regression-were compared for accuracy in
      predicting the presence or absence of pulmonary embolism on subsequent pulmonary
      arteriography. RESULTS: No significant difference was observed between the two
      methods. Areas under the receiver operating characteristic curves +/- standard
      deviation were 0.78 +/- 0.02 for the artificial neural network model and 0.79 +/-
      0.02 for the logistic regression model. Furthermore, use of these two methods
      resulted in no more diagnostic accuracy than did the use of a simple threshold
      model based only on the number of subsegmental perfusion defects, which was the
      dominant input variable. CONCLUSION: In the study population, the usefulness of
      data from ventilation-perfusion scans as predictors of the presence of a
      pulmonary embolism was similar for the three analytic methods, a finding that
      reinforces the importance of making comparisons to simpler or more established
      methods when performing studies involving complex analytic models, such as
      artificial neural networks.

PMID- 12239028
TI  - Comparison of quality of multiplanar reconstructions and direct coronal
      multidetector CT scans of the lung.
AB  - OBJECTIVE: The purpose of this study was to compare the quality of coronal
      multiplanar reconstructions with the quality of direct coronal thin-section
      multidetector CT (MDCT) scans. MATERIALS AND METHODS: Axial multidetector CT
      (MDCT) scans were obtained through the entire lung in 10 normal autopsy lung
      specimens using an MDCT scanner. Four protocols were used: 0.5-mm collimation
      with a 0.5-mm reconstruction interval; 0.5-mm collimation with a 0.3-mm
      reconstruction interval; 1-mm collimation with a 0.5-mm reconstruction interval;
      and 2-mm collimation with a 1-mm reconstruction interval. Multiplanar
      reconstruction images with 0.5-mm slice thickness were obtained from the four
      types of data sets. Direct coronal thin-section CT of the same 10 autopsy lung
      specimens was performed using 0.5-mm scan collimation, a 0.3-mm reconstruction
      interval, a 25.6-cm field of view, and a 512 x 512 matrix. Two independent
      observers compared the image quality of each of the four coronal multiplanar
      reconstruction sets with that of direct coronal thin-section CT scans. The
      observers analyzed visualization of anatomic features and artifacts. RESULTS: The
      total image quality of the multiplanar reconstructions obtained from 0.5-mm
      collimation data with or without 0.3-mm overlapping reconstruction was equal to
      that of direct coronal thin-section CT scans in all 20 interpretations. The image
      quality of multiplanar reconstruction images from 0.5-mm collimation data either
      with or without overlapping reconstruction was superior to multiplanar
      reconstruction images obtained from 1- or 2-mm collimation scans (p < 0.01,
      Fisher's exact test). Stairstep artifacts in multiplanar reconstructions using
      0.5-mm collimation without overlapping reconstruction were equal to those with
      overlapping reconstruction and were fewer than those on 1- or 2-mm collimation (p
      < 0.01, Mann-Whitney U test). CONCLUSION: The image quality of coronal
      multiplanar reconstructions from isotropic voxel data obtained using 0.5-mm
      collimation, with or without overlapping reconstruction, is similar to that of
      direct coronal thin-section CT scans.

PMID- 12239029
TI  - Radiologic-pathologic conference of Keller Army Community Hospital at West Point,
      the United States Military Academy: synovial sarcoma of the chest wall.

PMID- 12239031
TI  - Hermansky-Pudlak syndrome: radiography and CT of the chest compared with
      pulmonary function tests and genetic studies.
AB  - OBJECTIVE: The objective of our study was to describe the chest radiographic and
      high-resolution CT findings in patients with Hermansky-Pudlak syndrome and to
      correlate the radiologic findings with age, causative gene, and pulmonary
      function. SUBJECTS AND METHODS: Sixty-seven patients with Hermansky-Pudlak
      syndrome underwent high-resolution CT of the chest. A scoring system based on the
      extent of pulmonary involvement and specific high-resolution CT findings was
      used, and the findings were compared with patient age and the results of
      pulmonary function and genetic studies. Fifty-eight (87%) of the 67 patients also
      underwent chest radiography. These radiographs were compared with the high
      resolution CT scans. RESULTS: High-resolution CT was more sensitive than chest
      radiography in evaluating the extent of pulmonary disease in patients with
      Hermansky-Pudlak syndrome. All patients with mild findings on high-resolution CT
      scans had normal findings on chest radiographs. Common chest radiographic
      findings included reticulonodular interstitial pattern, perihilar fibrosis, and
      pleural thickening. High-resolution CT showed septal thickening, ground-glass
      opacities, and peribronchovascular thickening. For patients with Hermansky-Pudlak
      syndrome who were 30 years old or younger, high-resolution CT findings were
      usually minimal. Among patients who were older than 30 years, the 34 patients
      with HPS1 mutations had a score of 1.38+/-0.18 (mean+/-standard error of the
      mean) on high-resolution CT. This score is significantly greater than the score
      for the 11 patients without HPS1 mutations (0.36 +/- 0.15) (p < 0.001). The score
      based on high-resolution CT findings inversely correlated with percentage of
      forced vital capacity and was useful in defining the progression of interstitial
      disease. CONCLUSION: High-resolution CT provides a good radiologic monitor of
      disease status and progression in patients with Hermansky-Pudlak syndrome and
      correlates well with patient age, extent of pulmonary dysfunction, and genetic
      findings.

PMID- 12239030
TI  - Using the World Health Organization Classification of thymic epithelial neoplasms
      to describe CT findings.
AB  - OBJECTIVE: Our purpose was to assess the CT features of various subtypes of
      thymic epithelial neoplasms on the basis of the 1999 World Health Organization
      classification. MATERIALS AND METHODS: Thymic epithelial neoplasms in 53 patients
      who underwent thymectomy were retrospectively assessed histologically according
      to the 1999 World Health Organization classification. Type A and B neoplasms
      correspond to thymomas and type C, to thymic carcinoma. The study included four
      patients with type A, 14 with type AB, nine with type B1, 14 with type B2, four
      with type B3, and eight with type C epithelial tumors. Two observers
      independently assessed the CT scans without knowledge of the histologic findings.
      RESULTS: Type A tumors were more likely to have smooth contours on CT (4/4, 100%)
      and round shapes (3.5/4, 88%) than any other type of thymic epithelial tumor
      (all, p < 0.05). Type C tumors had a higher prevalence of irregular contours
      (6/8, 75%) than any other type of thymic epithelial tumor (all, p < 0.05).
      Calcification was more frequently seen in type B1 (4/9, 44%), type B2 (8.5/14,
      61%), and type B3 (3/4, 75%) tumors than in type AB (2/14, 14%) and type C
      (0.5/8, 6%) tumors (all, p < 0.05). CONCLUSION: Smooth contours and a round shape
      are most suggestive of type A thymic epithelial tumor, whereas irregular contours
      are most suggestive of type C tumor. Calcification is suggestive of type B
      tumors. CT is of limited value, however, in differentiating type AB, B1, B2, and
      B3 tumors.

PMID- 12239033
TI  - Thrombotic microangiopathy of pulmonary tumors: a vascular cause of tree-in-bud
      pattern on CT.

PMID- 12239032
TI  - Focal pulmonary interstitial opacities adjacent to thoracic spine osteophytes.
AB  - OBJECTIVE: The purpose of our study was to determine whether osteophytes of the
      thoracic vertebrae cause focal fibrosis in the subpleural region. CONCLUSION:
      Osteophytes of the thoracic vertebrae appear to cause focal fibrosis in the
      adjacent pulmonary tissue.

PMID- 12239035
TI  - Improved visualization of coronary arteries using a new three-dimensional
      submillimeter MR coronary angiography sequence with balanced gradients.
AB  - OBJECTIVE: The goal of our study was to evaluate a new three-dimensional real
      time navigator MR coronary angiography sequence to noninvasively visualize the
      coronary arteries. SUBJECTS AND METHODS: Fifteen healthy volunteers underwent MR
      coronary angiography with a new balanced turbo field-echo sequence in comparison
      with the standard turbo field-echo sequence. Signal-to-noise, blood-to
      myocardium, blood-to-fat, and blood-to-pericardial fluid contrast ratios of the
      left and right coronary artery systems were measured. Image quality was graded,
      the length and diameter of the coronary arteries were measured, and the number of
      visible side branches was assessed. RESULTS: The balanced turbo field-echo images
      yielded a higher blood-to-myocardium and blood-to-pericardial fluid contrast
      ratio, a similar blood-to-fat contrast ratio, and a lower signal-to-noise ratio
      than the turbo field-echo images. On a 5-point grading scale (1, nondiagnostic or
      unreadable; 2, poor; 3, moderate; 4, good; 5, excellent), image quality was rated
      significantly better for the balanced turbo field-echo sequence than for the
      turbo field-echo sequence (left coronary artery, 4.0 +/- 0.6 vs 3.6 +/- 0.5 [p =
      0.015]; right coronary artery, 4.4 +/- 0.4 vs 3.6 +/- 0.4 [p < 0.0001],
      respectively), resulting in a significantly longer segment of the three major
      coronary arteries visualized (left anterior descending coronary artery, 92 +/- 21
      mm vs 79 +/- 24 mm; left circumflex coronary artery, 70 +/- 7 mm vs 60 +/- 18 mm;
      right coronary artery, 112 +/- 28 mm vs 95 +/- 27 mm) and a significantly higher
      number of side branches visualized (left anterior descending coronary artery, 2.9
      +/- 1.3 vs 1.5 +/- 1.3; left circumflex coronary artery, 2.1 +/- 1.7 vs 1.0 +/-
      1.2; right coronary artery, 3.7 +/- 1.7 vs 2.6 +/- 1.5). Mean imaging time per
      coronary artery was significantly shorter for the balanced turbo field-echo
      sequence (5.7 +/- 1.0 min) than for the turbo field-echo sequence (8.4 +/- 1.4
      min) (p < 0.0001). CONCLUSION: Compared with standard turbo field-echo MR
      coronary angiography, optimized balanced turbo field-echo MR coronary angiography
      improves the visualization of the coronary arteries and their side branches
      within a significantly shorter imaging time.

PMID- 12239036
TI  - Noninvasive visualization of coronary arteries using contrast-enhanced
      multidetector CT: influence of heart rate on image quality and stenosis
      detection.
AB  - OBJECTIVE: Although multidetector CT (MDCT) with retrospectively ECG-gated image
      reconstruction has been shown to permit noninvasive visualization of the coronary
      arteries, the 125-250 msec required for image acquisition frequently causes
      motion artifacts. We investigated the influence of a patient's heart rate on the
      presence of motion artifacts and on accuracy of stenosis detection on contrast
      enhanced MDCT. MATERIALS AND METHODS: In 100 patients, MDCT was performed, and
      ECG-gated cross-sectional images were retrospectively reconstructed. From the 10
      data sets obtained for each patient (reconstructed at 0-90% of the cardiac cycle
      in increments of 10%), we chose the best data set for every coronary artery. The
      images of the arteries were evaluated for occurrence of artifacts and the
      presence of high-grade stenosis (diameter reduction exceeding 70%) or occlusions.
      MDCT results were compared with coronary angiographic findings. RESULTS: Of the
      400 coronary arteries, 115 (29%) could not be evaluated because of motion
      artifacts (n = 84) or other reasons (n = 31). Overall, 51 (49%) of 104 stenoses
      were revealed on MDCT. For detecting stenosis in those arteries that we could
      evaluate, MDCT had a sensitivity of 91% (51 of 56 stenoses detected) and a
      specificity of 89%. As the heart rate increased, the number of arteries that
      could be evaluated decreased, and overall sensitivity for stenosis detection
      decreased from 62% (heart rate < or = 70 beats per minute) to 33% (heart rate >
      70 beats per minute). CONCLUSION: MDCT can reveal coronary stenoses, but the
      usefulness of MDCT as an aid in accurately evaluating stenoses decreases as a
      patient's heart rate increases.

PMID- 12239037
TI  - Time course of perception and decision making during mammographic interpretation.
AB  - OBJECTIVE: This article describes the time course of lesion detection on digital
      mammograms using data about both eye position and decision time to compare
      performance between experienced mammographers and trainees. Research indicates
      that a longer decision time works against performance in the interpretation of
      chest radiographs because the likelihood of error is increased, particularly for
      trainees. Is this relation between decision time and performance also true for
      interpreting mammograms? Is there an optimal decision time-performance trade-off
      for detecting breast lesions? MATERIALS AND METHODS: Six radiology trainees
      (experience, 302-976 cases) and three mammographers (experience, 3000-5000 cases
      per year) reviewed 40 test cases. Each test case was represented by two
      mammograms that showed different views of the same breast. Twenty breasts
      contained suspicious lesions, and 20 were lesion-free. An interactive computer
      display system with an eye-head tracker measured the timing of decisions, where
      visual attention was directed, and how much time was spent fixating on a region
      of interest for each decision. Eye position was monitored during an initial
      decision phase, and decision times were measured throughout a final-decision
      phase during which suspicious lesions recognized initially were interpreted and
      localized. Performance was analyzed using localization receiver operating
      characteristic curves. RESULTS: The time course of interpreting mammograms is
      similar to that for interpreting chest radiographs. Mammographers detected 71% of
      the true lesions within 25 sec, and trainees detected 46% within 40 sec. Both a
      fixation dwell time of 1000 msec and a high level of confidence in the decision
      were associated with the detection of true lesions for the mammographers but not
      for the trainees. CONCLUSION: Mammographers detected most breast lesions by
      global recognition within 25 sec, but trainees took more time. Prolonging one's
      search beyond the global recognition phase yielded few new lesions and increased
      the risk of error.

PMID- 12239038
TI  - Pseudoaneurysm of the breast related to 18-gauge core biopsy: successful repair
      using sonographically guided thrombin injection.

PMID- 12239039
TI  - Invasive micropapillary carcinoma of the breast: clinical, mammographic, and
      sonographic findings with histopathologic correlation.
AB  - OBJECTIVE: The purpose of our study was to investigate the imaging features of
      invasive micropapillary carcinoma of the breast, which is a recently described,
      rare variant of infiltrating ductal carcinoma. CONCLUSION: Invasive
      micropapillary carcinoma of the breast usually manifests as a firm, immobile
      mass. Findings on mammography are of a spiculated, irregular or round, high
      density mass with or without associated microcalcifications. On sonography, the
      common findings are of a homogeneously hypoechoic, irregular or microlobulated
      mass with posterior acoustic shadowing or normal sound transmission. Axillary
      lymph nodes are frequently involved. Although these findings are not specific and
      may be seen with other breast malignancies, invasive micropapillary carcinoma
      should be included in the differential diagnosis for breast masses with these
      imaging features. Also, radiologic findings may help in the histopathologic
      differentiation of cases that are difficult to diagnose, such as metastatic
      tumors.

PMID- 12239041
TI  - Skin and thyroid dosimetry in cervical spine screening: two methods for
      evaluation and a comparison between a helical CT and radiographic trauma series.
AB  - OBJECTIVE: The first objective of this study was to test the hypothesis that
      estimates of radiation dose from an ionization chamber correspond to
      thermoluminescent dosimeter measurements in patients with suspected cervical
      spine injury. The second objective was to compare the radiation dose of a
      protocol using helical CT of the entire cervical spine with that of a protocol
      using radiography alone. SUBJECTS AND METHODS: Thermoluminescent dosimeter
      measurements of radiation dose to the skin over the thyroid were made in two
      patient groups: six patients evaluated with CT of the cervical spine and six
      patients evaluated with radiography. The skin dose for both groups was estimated
      with an ionization chamber, and the thermoluminescent dosimeter measurements and
      ionization chamber estimates of skin dose were compared for both groups. Using
      the ionization chamber, we estimated the radiation dose to the thyroid for all 12
      patients. With these estimates, we computed the ratios of skin dose and thyroid
      dose (CT / radiography). RESULTS: Thermoluminescent dosimeter measurements
      correlated with ionization chamber estimates of skin dose in both patient groups.
      Using the ionization chamber estimates, we found that CT delivered 26.0 mGy to
      the thyroid. In the patients evaluated with radiography, the mean thyroid dose
      was 1.80 mGy (95% confidence interval, 1.05-2.55 mGy). Ionization chamber dose
      ratios (CT / radiography) for the skin and thyroid were 9.69 and 14.4 mGy,
      respectively. CONCLUSION: The correlation between the ionization chamber
      estimates and the thermoluminescent dosimeter measurements supports the use of
      ionization chamber estimates in future research. Although helical CT of the
      entire cervical spine is cost-effective in patients at high risk for fracture,
      the greater than 14-fold increase in the radiation dose to the thyroid emphasizes
      the importance of clinical stratification to identify patients at high risk for
      fracture and the judicious use of CT in patients with suspected cervical spine
      injury.

PMID- 12239042
TI  - Tendon involvement in pedal infection: MR analysis of frequency, distribution,
      and spread of infection.
AB  - OBJECTIVE: The objective of our study was to evaluate the frequency,
      distribution, and extent of tendon involvement in patients with pedal infections.
      MATERIALS AND METHODS: Contrast-enhanced MR imaging examinations of 159 infected
      feet performed at 1.5 T were reviewed by two musculoskeletal radiologists for the
      presence and location of tendon infection (peritendinous enhancement contiguous
      to an adjacent ulcer or cellulitis) and for the spread of infection along
      tendons, which was defined as peritendinous contrast enhancement extending more
      than 2 cm beyond surrounding cellulitis. The study group was composed of 156
      consecutive patients, 82.7% of whom had diabetes; all patients underwent
      subsequent surgical treatment. Results of MR evaluations were compared with the
      patients' charts and surgical reports. RESULTS: Of the 129 MR examinations
      showing an infection in the forefoot, MR evidence of tendon involvement in the
      infection was observed in 56 MR examinations (43%). The sum of involved tendons
      per ray was as follows: first ray (flexor tendon, n = 19; extensor tendon, n =
      13), second (flexor tendon, n = 12; extensor tendon, n = 7), third (flexor
      tendon, n = 5; extensor tendon, n = 4), fourth (flexor tendon, n = 5; extensor
      tendon, n = 1), and fifth (flexor tendon, n = 11; extensor tendon, n = 6). Of the
      32 MR examinations showing infection in the hindfoot, 14 examinations (44%)
      showed evidence of tendon involvement, most frequently of the distal Achilles
      tendon (n = 7). MR evidence of the spread of infection along a tendon was seen in
      12 examinations, always with proximal spread of infection; and infection led to
      the development of an abscess in the central plantar compartment in three
      patients. Intraoperative evidence of a tendon infection was documented in 11
      patients. The surgical procedure was altered because of the tendon infection in
      six patients. CONCLUSION: MR evidence of tendon infection is present in
      approximately half the patients who require surgery for pedal infection. Evidence
      of spread of the infection along tendons is seen infrequently on MR imaging.
      Detection of a tendon infection could influence surgical therapy.

PMID- 12239043
TI  - Sonography of ankle tendon impingement with surgical correlation.
AB  - OBJECTIVE: This report describes sonography of ankle tendon impingement due to
      osteophytes, fracture fragments, and orthopedic hardware. CONCLUSION: Sonography
      can be helpful in identifying ankle tendon impingement due to osteophytes,
      fracture fragments, and orthopedic hardware. In such cases, dynamic sonography
      can aid assessment.

PMID- 12239045
TI  - Symphyseal cleft injection in the diagnosis and treatment of osteitis pubis in
      athletes.
AB  - OBJECTIVE: The purpose of this study was to describe the application, technique,
      and results of symphyseal cleft injection in athletes with osteitis pubis.
      CONCLUSION: Symphyseal cleft injection is a useful technique for the diagnosis
      and treatment of osteitis pubis in athletes. The procedure is well tolerated and
      may facilitate early resumption of competitive duties.

PMID- 12239046
TI  - Quantification of skeletal involvement in adults with type I Gaucher's disease:
      fat fraction measured by Dixon quantitative chemical shift imaging as a valid
      parameter.
AB  - OBJECTIVE: The objective of our study was to determine the merit of the fat
      fraction of axial bone marrow measured by Dixon quantitative chemical shift
      imaging (Dixon QCSI) as a clinical parameter to quantitatively assess the extent
      of skeletal involvement in type 1 Gaucher's disease. MATERIALS AND METHODS: Dixon
      QCSI was performed in 30 adult patients (age range, 18-69 years; mean, 39 years)
      with type 1 Gaucher's disease who were untreated. The relationship between the
      mean value of the fat fraction in vertebrae L3, L4, and L5 and the presence,
      absence, and severity of clinical bone complications (chronic bone pain, bone
      crisis, fracture, avascular necrosis, and joint replacement) as well as the
      conventional MR imaging of bone marrow involvement were studied. Also the
      relationship of fat fraction to sex, age, and other disease parameters (history
      of splenectomy, liver and spleen volume, plasma chitotriosidase, hemoglobin
      level, and platelet count) was evaluated. Our results were compared with the fat
      fraction of healthy volunteers. RESULTS: The fat fraction measured in patients
      with Gaucher's disease ranged from 0.08 to 0.40 (mean, 0.20). Bone complications
      occurred primarily in patients with a fat fraction of less than 0.23. Univariate
      logistic regression analysis indicated that for every decrease of 0.1 of the fat
      fraction, the risk of bone complications increased 85% (p < 0.05). The fat
      fraction was correlated with liver size, but no correlation with other disease
      parameters was found. In the patient population, the fat fraction was
      significantly lower than in the healthy population (range, 0.27-0.55; mean, 0.37;
      p < 0.001). CONCLUSION: The fat fraction of the lumbar spine when measured with
      Dixon QCSI is associated with the occurrence of bone complications. It may,
      therefore, be a clinically useful parameter.

PMID- 12239048
TI  - Whole-body MR imaging in the diagnosis of polymyositis.
AB  - OBJECTIVE: Our purpose was to evaluate the use of whole-body MR imaging in the
      assessment of the extent and distribution of muscle inflammation in patients with
      polymyositis. CONCLUSION: Whole-body turbo short tau inversion recovery imaging
      is a convenient complete method of evaluating patients with muscle inflammation
      caused by polymyositis. This imaging technique allows us to evaluate the total
      inflammatory burden by revealing multiple muscle groups not seen with standard
      protocols.

PMID- 12239049
TI  - Radiologic manifestations of proximal-type epithelioid sarcoma of the soft
      tissues.
AB  - OBJECTIVE: Our study was conducted to summarize the clinical and radiologic
      presentations and imaging features of proximal-type epithelioid sarcoma, a rare
      aggressive soft-tissue sarcoma, in 16 patients. CONCLUSION: The chest wall,
      inguinal region, thigh, and perineum were the most common sites of the disease.
      Tumors exhibited multilobulated contours in 87.5% of the patients, which may be
      suggestive of this tumor type. Nodal involvement was identified on CT and MR
      imaging and confirmed pathologically in 62.5% of the patients. Although CT or MR
      findings are nonspecific, proximal-type epithelioid sarcoma shows a multinodular
      configuration and admixes with regional lymph node metastasis on imaging studies.

PMID- 12239050
TI  - Spectrum of MR imaging findings in spinal tuberculosis.

PMID- 12239052
TI  - Physiologic subperiosteal new bone formation: prevalence, distribution, and
      thickness in neonates and infants.
AB  - OBJECTIVE: The objective of our study was to determine the prevalence,
      distribution, and thickness of physiologic subperiosteal new bone formation in
      neonates and infants. MATERIALS AND METHODS: High-detail postmortem skeletal
      radiologic surveys of 101 neonates and infants who had died from sudden infant
      death syndrome were reviewed. The average age at the time of death was 2.6 months
      (range, 2 weeks-8 months 2 weeks). The location, distribution, and thickness of
      subperiosteal new bone formation of the long bones were noted and measured with
      an ocular magnification system. RESULTS: subperiosteal new bone formation was
      identified in 35 infants (35%), all of whom were between 1 and 4 months of age.
      The prevalence of subperiosteal new bone formation involving one or more bones
      was 37% for ages 1-2 months, 55% for ages 2-3 months, and 35% for ages 3-4
      months. subperiosteal new bone formation involved the tibia in 29 infants
      (bilateral involvement in 19) and the femurs in 14 infants (bilateral involvement
      in 11). The humerus was a site of subperiosteal new bone formation in 12 infants;
      the ulna, in seven infants; and the radius, in two infants. The thickness of the
      subperiosteal new bone formation was never more than 1.8 mm, and the average
      thickness for the various long bones ranged from 0.7 to 0.9 mm. CONCLUSION: Our
      results suggest that subperiosteal new bone formation is a common finding in
      infants 1-4 months of age. It is potentially an abnormal finding in neonates (CI
      = 0.0, 0.007) and in infants older than 4 months of age (CI = 0.0, 0.003). A
      thickness of 2 mm or more in subperiosteal new bone formation is likely to be
      abnormal and should prompt further diagnostic evaluation.

PMID- 12239053
TI  - MR imaging of primary skeletal muscle diseases in children.

PMID- 12239054
TI  - Cerebrovascular disease in HIV-infected pediatric patients: neuroimaging
      findings.
AB  - OBJECTIVE: The goal of our study was to report on the prevalence and the
      neuroradiologic manifestations of cerebrovascular complications in children
      infected with HIV. We also elucidate the types of vascular involvement, identify
      their anatomic distribution, and discuss possible causes. MATERIALS AND METHODS:
      We conducted a retrospective study of 567 patients (age range, 1 month-29 years;
      median age, 5.47 years) who acquired HIV as children. Of these, 426 patients
      (75%) were evaluated with neuroimaging studies. We reviewed these studies to
      identify the cerebrovascular abnormalities and classify them by type, anatomic
      location, and shape. RESULTS: Eleven children (2.6%) were found to have
      cerebrovascular lesions. Only one had focal neurologic symptoms at the time of
      diagnosis. Twenty-six aneurysms were found in seven patients, and 27 infarctions
      were found in eight patients. In four of the patients with infarctions, fusiform
      aneurysms of the cerebral arteries were also identified. Most patients had
      advanced HIV disease. Nine of the 11 patients were infected by a vertical
      transmission route or during blood transfusion early in the neonatal period. In
      this group of patients, the diagnosis of cerebrovascular disease was made earlier
      (mean age at diagnosis, 8.2 years) than in the two patients who were infected
      later in life (mean age at diagnosis, 14.9 years). CONCLUSION: HIV-infected
      children have an increased incidence of cerebrovascular disease that is
      associated with severe immune suppression and with vertically acquired HIV
      infection or exposure to the virus in the neonatal period. Despite extensive
      lesions, most children in our study were asymptomatic. Screening with MR imaging
      should be considered for high-risk children and is advisable when evidence of
      neurologic symptoms or neurocognitive dysfunction is noted.

PMID- 12239055
TI  - Using morphologic parameters of extraocular muscles for diagnosis and follow-up
      of Graves' ophthalmopathy: diameters, areas, or volumes?
AB  - OBJECTIVE: The objective of this study was to find the most appropriate,
      accurate, and convenient muscle parameter that can be used as a substitute for
      volume in monitoring the effectiveness of therapy of patients with Graves'
      ophthalmopathy. SUBJECTS AND METHODS: The four rectus muscles in 110 orbits (35
      patients and 20 control subjects) were evaluated with MR imaging. The diameter at
      the largest extent of the muscle belly, as well as the long and the short
      diameters and the cross-sectional areas in a preselected coronal scan, were
      measured for each muscle and were compared with the corresponding muscle volume
      measured on contiguous T1-weighted transverse slices. RESULTS: The measured
      coronal area correlated well with the volume of the superior (r = 0.694, p <
      0.0001) and inferior (r = 0.783, p < 0.0001) recti, and the largest transverse
      diameter showed strong correlation with the volume of the lateral (r = 0.868, p <
      0.0001) and medial (r = 0.869, p < 0.0001) recti. For the latter muscle, the
      coronal area also exhibited a good correlation with the volume (r = 0.838, p <
      0.0001). Coronal cross-sectional areas can be well estimated by measuring both
      the short and long coronal muscle diameters (r values were between 0.914 and
      0.966; p < 0.0001). CONCLUSION: In Graves' ophthalmopathy, the volume of three of
      the rectus muscles can be well estimated by simple measurements on a single
      coronal slice, and the largest transverse diameter of the lateral rectus is
      suitable for the same purpose.

PMID- 12239057
TI  - Peripheral vascular occlusive disease: evaluation with contrast-enhanced moving
      bed MR angiography versus digital subtraction angiography in 106 patients.
AB  - OBJECTIVE: The purpose of our study was to compare contrast-enhanced moving-bed
      MR angiography and digital subtraction angiography in the evaluation of
      peripheral vascular occlusive disease. MATERIALS AND METHODS: This retrospective
      report includes 106 patients (45 women, 61 men) with known or suspected
      peripheral vascular occlusive disease who underwent MR angiography and
      intraarterial digital subtraction angiography of the peripheral arteries. MR
      angiography was performed on a 1.0-T unit using a moving-bed technique. Every leg
      was divided into 14 vascular segments, and severity of disease was scored in four
      categories. Digital subtraction angiography was the standard of reference.
      RESULTS: In the 106 patients, 2378 vessel segments were evaluated with both
      imaging modalities. In 2156 segments, MR angiography and digital subtraction
      angiography were concordant for stenosis classification, in 188 segments the two
      modalities differed in one category, and in 24 segments they differed in two
      categories. MR angiography achieved sensitivity and specificity of 96.7% and
      95.8%, respectively, for differentiating nonsignificant from hemodynamically
      significant stenosis (kappa = 0.91). CONCLUSION: This study indicates that MR
      angiography is an accurate imaging modality in clinical practice. Our data
      support the concept that MR angiography can modify the diagnosis of suspected
      peripheral vascular occlusive disease.

PMID- 12239059
TI  - Gadolinium-enhanced digital subtraction angiography of hemodialysis fistulas: a
      diagnostic and therapeutic approach.
AB  - OBJECTIVE: The aim of our study was to evaluate the feasibility, safety, and
      potential role of the contrast agent gadoterate meglumine for digital subtraction
      angiography as a single diagnostic procedure or before percutaneous transluminal
      angioplasty of malfunctioning native dialysis fistulas. MATERIALS AND METHODS:
      Over a 20-month period, 23 patients (15 women, eight men) with an age range of 42
      87 years (mean, 63 years) having end-stage renal insufficiency and with recent
      hemodialysis fistula surgical placement underwent gadoterate-enhanced digital
      subtraction angiography with a digital 1024 x 1024 matrix. Opacification was
      performed on the forearm, arm, and chest with the patient in the supine position
      using an injection (retrograde, n = 14; anterograde, n = 8; arterial, n = 1) of
      gadoterate meglumine into the perianastomotic fistula segment at a rate of 3
      mL/sec for a total volume ranging from 24 to 32 mL. Percutaneous transluminal
      angioplasty was performed in three patients and required an additional 8 mL per
      procedure. Examinations were compared using a 3-step confidence scale and a two
      radiologist agreement (Cohen's kappa statistic) for diagnostic and opacification
      quality. Tolerability was evaluated on the basis of serum creatinine levels and
      the development of complications. RESULTS: No impairment of renal function was
      found in the 15 patients who were not treated with hemodialysis. Serum creatinine
      level change varied from -11.9% to 11.6%. All studies were of diagnostic quality.
      The presence of stenosis (n = 14) or thrombosis (n = 3) in arteriovenous fistulas
      was shown with good interobserver agreement (kappa = 0.71-0.80) in relation to
      opacification quality (kappa = 0.59-0.84). No pain, neurologic complications, or
      allergiclike reactions occurred. Three percutaneous transluminal angioplasty
      procedures (brachiocephalic, n = 2; radiocephalic, n = 1) were successfully
      performed. CONCLUSION: Gadoterate-enhanced digital subtraction angiography is an
      effective and safe method to assess causes of malfunction of hemodialysis
      fistulas. It can also be used to plan and perform percutaneous transluminal
      angioplasty.

PMID- 12239060
TI  - CT of prominent pericolic or perienteric vasculature in patients with Crohn's
      disease: correlation with clinical disease activity and findings on barium
      studies.
AB  - OBJECTIVE. The purpose of this study was to correlate CT findings of prominent
      pericolic or perienteric vasculature with clinical disease activity, treatment
      methods, and barium enema study findings in patients with Crohn's disease.
      MATERIALS AND METHODS: We retrospectively analyzed 33 patients with Crohn's
      disease who had undergone both barium enema study and abdominal CT. CT scans were
      evaluated for the presence and location of prominent vasculature. On the basis of
      the Crohn's disease activity index, the patients were assigned to one of three
      categories--active, intermediate, or quiescent disease groups--and the frequency
      of prominent vasculature was compared among them. Thereafter, erythrocyte
      sedimentation rates, C-reactive protein levels, treatment methods, and
      radiographic findings were compared in groups with and without prominent
      vasculature. RESULTS: Prominent vasculature was more frequently found in patients
      with active disease (81%) than in those with intermediate (33%) and quiescent
      disease (0%) (p < 0.001). The erythrocyte sedimentation rates and C-reactive
      protein levels were higher in patients with prominent vasculature (but not at a
      statistically significant rate). Patients with prominent vasculature were more
      frequently admitted to the hospital (p = 0.024) and received more aggressive
      treatment (p = 0.049) than patients without prominent vasculature. The main
      differences of radiographic findings between the group with prominent vasculature
      and the group without prominent vasculature included the common occurrence of
      longitudinal and perpendicular ulceration (p = 0.017 for small bowel; p = 0.041
      for colon) and the extensive length of organ involvement (p = 0.004 for small
      bowel; p = 0.036 for colon). CONCLUSION: Prominent pericolic or perienteric
      vasculature seen on CT in patients with Crohn's disease suggests that the disease
      is clinically active, advanced, and extensive and that these patients require
      more aggressive treatment than patients without this CT finding.

PMID- 12239061
TI  - CT findings in the abdomen and pelvis after gastric carcinoma resection.

PMID- 12239062
TI  - Diffuse cavernous hemangiomatosis of the colon: findings on three-dimensional CT
      colonography.

PMID- 12239063
TI  - Detection of malignant hepatic lesions before orthotopic liver transplantation:
      accuracy of ferumoxides-enhanced MR imaging.
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic accuracy of
      ferumoxides-enhanced MR imaging for screening malignant hepatic lesions before
      orthotopic liver transplantation. MATERIALS AND METHODS: The study comprised 48
      patients who underwent MR imaging within 6 months before transplantation. Imaging
      techniques included unenhanced and ferumoxides-enhanced T1-weighted gradient-echo
      and T2-weighted fast spin-echo sequences and ferumoxides-enhanced T2(*)-weighted
      gradient-echo sequences. Qualitative and quantitative analyses were performed;
      the gold standard was the histopathologic reports of explanted livers. RESULTS:
      Twenty patients had malignant hepatic lesions, and 24 hepatocellular carcinomas
      were histopathologically proven. The mean area under the receiver operating
      characteristic curve and the mean sensitivity were significantly greater for the
      image sets with ferumoxides-enhanced gradient-echo sequences than for those
      without these sequences. The mean sensitivity and specificity of all sequences
      were 85% and 74% on a per-patient basis, respectively. The mean contrast-to-noise
      ratio was significantly greater for the ferumoxides-enhanced T2(*)-weighted
      gradient-echo sequences than for any other sequences and for the ferumoxides
      enhanced T1-weighted gradient-echo sequences than for unenhanced sequences and
      the ferumoxides-enhanced T2-weighted fast spin-echo sequences. CONCLUSION:
      Ferumoxides-enhanced gradient-echo sequences improved the diagnostic accuracy and
      the sensitivity for detecting malignant hepatic lesions in patients with end
      stage cirrhosis of the liver. However, the specificity was not improved even
      after the administration of ferumoxides because of the false-positive lesions
      that were mainly the result of fibrotic changes.

PMID- 12239064
TI  - Caroli's disease: radiologic spectrum with pathologic correlation.
AB  - OBJECTIVE: The purpose of our study was to describe the spectrum of radiologic
      and pathologic features of Caroli's disease. CONCLUSION: Caroli's disease and its
      complications have overlapping radiologic appearances that reflect the underlying
      pathology of fibrosis, ductal dilatation, cholangitis, stone formation, and
      malignancy.

PMID- 12239065
TI  - Cystic changes in hepatic metastases from gastrointestinal stromal tumors (GISTs)
      treated with Gleevec (imatinib mesylate).
AB  - OBJECTIVE: The purpose of this article is to illustrate the CT findings in
      patients with hepatic metastases from a gastrointestinal stromal tumor who were
      treated with STI-571. CONCLUSION: Hepatic metastases from gastrointestinal
      stromal tumors that respond to treatment with STI-571 can appear as near-cystic
      components with well-defined borders on contrast-enhanced CT. Most metastases
      became smaller. These metastases resemble simple cysts, but density measurements
      may differentiate them from one another.

PMID- 12239066
TI  - MR obstetric pelvimetry: effect of birthing position on pelvic bony dimensions.
AB  - OBJECTIVE: The aim of our study was to measure the impact of supine and upright
      birthing positions on MR pelvimetric dimensions. MATERIALS AND METHODS: MR
      pelvimetry was performed in 35 nonpregnant female volunteers in an open 0.5-T MR
      imaging system with patients in the supine, hand-to-knee, and squatting
      positions. The obstetric conjugate; sagittal outlet; and interspinous,
      intertuberous, and transverse diameters were compared among positions. RESULTS:
      With patients in the hand-to-knee and squatting positions, the sagittal outlet
      (11.8 +/- 1.3 cm and 11.7 +/- 1.3 cm) exceeded that in the supine position (11.5
      +/- 1.3 cm; p = 0.002 and p = 0.01, respectively), as did the interspinous
      diameter (11.6 +/- 1.1 cm and 11.7 +/- 1.0 cm vs 11.0 +/- 0.7 cm; p < 0.0001, in
      both cases). Intertuberous diameter was wider with patients in the squatting
      position than in the supine position (12.7 +/- 0.8 cm vs 12.4 +/- 1.1 cm; p =
      0.01). Only the obstetric conjugate was smaller with patients in the upright
      squatting position than in the supine position (12.3 +/- 0.8 cm vs 12.4 +/- 0.9
      cm; p = 0.01). Transverse diameter did not change significantly in any position.
      CONCLUSION: An upright birthing position significantly expands female pelvic bony
      dimensions, suggesting facilitation of labor and delivery.

PMID- 12239067
TI  - Cystic adenomatoid tumor of the uterus.

PMID- 12239068
TI  - Targetlike focal spared area of the liver: definite imaging diagnosis.

PMID- 12239069
TI  - Mesenteric venous thrombosis.

PMID- 12239070
TI  - Negative predictive value of breast imaging in patients with palpable lesions.

PMID- 12239071
TI  - de Quervain disease.

PMID- 12239072
TI  - The "diaphanous" diaphragm: previously described.

PMID- 12239073
TI  - Testicular epidermoid cysts.

PMID- 12239075
TI  - MR imaging of acute trauma of the elbow.

PMID- 12239076
TI  - Mesenchymal chondrosarcoma of the maxilla.

PMID- 12239077
TI  - Scheuermann's disease of the lumbar spine in identical twins.

PMID- 12239078
TI  - MR imaging appearance of plantar eccrine acrospiroma (sweat gland tumor).

PMID- 12239079
TI  - Insights from insulin-like growth factor binding protein transgenic mice.
AB  - The existence of abundant high affinity binding proteins for the IGFs, the IGF
      binding proteins (IGFBPs), was first demonstrated more than 40 yr ago in the very
      early days of somatomedin research. With the development of molecular techniques
      and transgenic and knockout mouse models, the nature, complexity, and redundancy
      of the IGFBPs have now started to be elucidated. Indeed the functional role of
      the circulating IGFs and the originally proposed endocrine somatomedin hypothesis
      have recently been questioned. The limited reports to date indicate that IGFBP
      knockout mice have few phenotypic manifestations. In contrast, overexpression of
      IGFBPs in transgenic mice is associated with manifestations that provide some
      insight into the physiological role of the binding proteins. The predominant
      effect of generalized or tissue-specific overexpression of the IGFBPs has been
      growth inhibition as would be anticipated from inhibition of the actions of IGF-I
      and -II. In addition, impaired glucose homeostasis and reduced fecundity have
      been observed in both IGFBP-1- and IGFBP-3-overexpressing transgenic mice. This
      review examines the data reported to date for transgenic mouse models that
      overexpress IGFBPs. In addition, data from transgenic mice that overexpress the
      acid-labile subunit, an important component of the ternary complex, have also
      been reviewed.

PMID- 12239080
TI  - Impaired adaptive thermogenesis in pituitary adenylate cyclase-activating
      polypeptide-deficient mice.

PMID- 12239081
TI  - Islet function phenotype in gastrin-releasing peptide receptor gene-deficient
      mice.
AB  - Gastrin-releasing peptide (GRP) is an islet neuropeptide that stimulates insulin
      secretion. To explore whether islet GRP contributes to neurally mediated insulin
      secretion, we studied GRP receptor (GRPR)-deleted mice. By using RT-PCR we showed
      that GRPR mRNA is expressed in islets of wild-type mice, but is lost in GRPR
      deleted mice. Functional studies revealed that GRP potentiates glucose-stimulated
      insulin secretion in wild-type animals, but not in GRPR-deleted mice. This shows
      that GRPR is the receptor subtype mediating GRP-induced insulin secretion and
      that GRPR-deleted mice are tools for studying the physiological role of islet
      GRP. We found that GRPR-deleted mice display 1) augmentation of the insulin
      response to glucose by a mechanism inhibited by ganglionic blockade; 2) increased
      insulin responsiveness also to the cholinergic agonist carbachol, but not to
      arginine; 3) impaired insulin and glucagon responses to autonomic nerve
      activation by 2-deoxyglucose; 4) normal islet adaptation to high fat-induced
      insulin resistance and fasting; and 5) normal islet cytoarchitecture, as revealed
      by immunocytochemistry of insulin and glucagon. In conclusion, 1) GRPR is the
      receptor subtype mediating the islet effects of GRP; 2) GRP contributes to
      insulin secretion induced by activation of the autonomic nerves; and 3) deletion
      of GRPR is compensated by increased cholinergic sensitivity.

PMID- 12239082
TI  - Sex differences in progesterone receptor expression: a potential mechanism for
      estradiol-mediated sexual differentiation.
AB  - The differential exposure of males and females to testosterone (T) and its
      metabolite estradiol (E) contributes to the development of sex differences in the
      brain. However, the mechanisms by which T and E permanently alter neural
      development remain virtually unknown. Two regions of the rat preoptic area, the
      anteroventral periventricular nucleus (AVPv) and the medial preoptic nucleus
      (MPN), are sexually dimorphic and serve as models for studying the hormonal
      mechanisms of sexual differentiation. Around birth, these regions express
      dramatically higher levels of progesterone receptor immunoreactivity (PRir) in
      males than they do in females. The present study examined the possibility that
      sexually dimorphic induction of PR expression in these two regions constitutes a
      potential mechanism of E-mediated sexual differentiation. Prenatal exposure to
      either T propionate or the synthetic estrogen, diethylstilbestrol, but not
      dihydrotestosterone propionate, significantly increased PRir levels in the MPN
      and AVPv of fetal females compared with controls. Prenatal exposure to the
      aromatase inhibitor, 1,4,6-androstatriene-3,17-dione, significantly reduced PRir
      in the MPN and AVPv of fetal males, whereas the androgen receptor antagonist
      flutamide had no effect. This suggests that aromatization of T into E is crucial
      for the sex difference in PR expression in the MPN and AVPv during development.

PMID- 12239083
TI  - Characterization of rat100, a 300-kilodalton ubiquitin-protein ligase induced in
      germ cells of the rat testis and similar to the Drosophila hyperplastic discs
      gene.
AB  - Conjugation of ubiquitin to proteins is activated during spermatogenesis.
      Ubiquitination is mediated by ubiquitin-activating enzyme (E1), ubiquitin
      conjugating enzymes (UBCs or E2s), and ubiquitin protein ligases (E3s). Since we
      previously showed that the activated ubiquitination is UBC4 dependent, we
      characterized Rat100, a UBC4-dependent E3 expressed in the testis. Analysis of
      expressed sequence tag sequences and immunoblotting showed that Rat100 is
      actually a 300-kDa protein expressed mainly in the brain and testis and is
      similar to the human E3 identified by differential display (EDD) protein and the
      Drosophila hyperplastic discs gene, mutants of which cause a defect in
      spermatogenesis. Rat100 is induced during postnatal development of the rat
      testis, peaking at d 25. It is localized only in germ cells and is highly
      expressed in spermatocytes, moderately in round and slightly in elongating
      spermatids. In contrast to UBC4 whose removal from a testis extract abrogates
      much of the conjugation activity, immmunodepletion of Rat100 from the extracts
      had little effect. Rat100 therefore has a limited subset of substrates, some of
      which appear associated with the E3 as the immunoprecipitate containing Rat100
      supported incorporation of (125)I-ubiquitin into high molecular weight proteins.
      Thus, Rat100 is the homolog of human EDD and likely of Drosophila hyperplastic
      discs. This homology, together with our results, suggests that induction of this
      E3 results in ubiquitination of specific substrates, some of which are important
      in male germ cell development.

PMID- 12239084
TI  - Does cortisol mediate endotoxin-induced inhibition of pulsatile luteinizing
      hormone and gonadotropin-releasing hormone secretion?
AB  - Bacterial endotoxin (lipopolysaccharide), a commonly used model of
      immune/inflammatory stress, inhibits reproductive neuroendocrine activity and
      concurrently induces a profound stimulation of the hypothalamo-pituitary-adrenal
      axis. We employed two approaches to test the hypothesis that enhanced secretion
      of cortisol mediates endotoxin-induced suppression of pulsatile GnRH and LH
      secretion in the ovariectomized ewe. First, we mimicked the endotoxin-induced
      increase in circulating cortisol by delivering the glucocorticoid in the absence
      of the endotoxin challenge. Within 1-2 h, experimentally produced increments in
      circulating cortisol suppressed pulsatile LH secretion in a dose-dependent
      fashion. Second, we blocked the endotoxin-induced stimulation of cortisol
      secretion using the drug metyrapone, which inhibits the 11-beta hydroxylase
      enzyme necessary for cortisol biosynthesis. In the absence of a marked
      stimulation of cortisol secretion, endotoxin still profoundly inhibited pulsatile
      GnRH and LH secretion. We conclude that, although enhanced cortisol secretion may
      contribute to endotoxin-induced suppression of reproductive neuroendocrine
      activity, the marked stimulation of the glucocorticoid is not necessary for this
      response. Our findings are consistent with the hypothesis that
      immune/inflammatory stress inhibits reproductive neuroendocrine activity via more
      than one inhibitory pathway, one involving enhanced secretion of cortisol and the
      other(s) being independent of this glucocorticoid.

PMID- 12239085
TI  - Transforming growth factor-beta stimulates vascular endothelial growth factor
      production by folliculostellate pituitary cells.
AB  - TGF-beta isoforms are expressed in the anterior pituitary and modulate the growth
      and function of endocrine pituitary cells. Recently, TGF-beta has been shown to
      stimulate growth and basic fibroblast growth factor secretion in nonendocrine
      folliculostellate (FS) pituitary cells. We therefore studied whether the
      production of FS cell-derived vascular endothelial growth factor (VEGF), the most
      important regulator of vascular permeability and angiogenesis, is affected by TGF
      beta. We observed by RT-PCR that TtT/GF cells, which are FS mouse pituitary tumor
      cells, synthesize TGF-beta1, -beta2, and -beta3. They also express TGF-beta
      receptors types 1 and 2, as well as Smad2, Smad3, and Smad4 proteins, which are
      essential for TGF-betabinding and signaling. Stimulation of TtT/GF cells with
      either TGF-beta1 or TGF-beta3 induced a rapid translocation of Smad2 into the
      cell nuclei. Both TGF-beta isoforms dose dependently stimulated VEGF production
      in TtT/GF cells, but not in lactosomatotroph GH3 cells. Time-course studies and
      suppression of TGF-beta-induced VEGF production by cycloheximide suggest that TGF
      beta induces de novo synthesis of VEGF in folliculostellate cells, which is
      completely blocked by dexamethasone. In primary rat pituitary cell cultures, TGF
      beta1 and -beta3 stimulated VEGF production. TGF-beta stimulation of VEGF
      production by folliculostellate cells could modulate intrapituitary vascular
      permeability and integrity as well as angiogenesis in an auto-/paracrine manner.

PMID- 12239086
TI  - Discrimination between signaling pathways in regulation of specific gene
      expression by insulin and growth hormone in hepatocytes.
AB  - Insulin and GH can activate common signaling elements in many tissues and cell
      lines. We investigated the possibility of overlap in signaling pathways activated
      by insulin and GH in a key target cell, the hepatocyte. In primary cultures of
      rat hepatocytes, GH caused a dose- and time-dependent increase in tyrosine
      phosphorylation of signal transducer and activator of transcription 5. This was
      accompanied by the induction of the mRNA encoding suppressor of cytokine
      signaling 2. Neither of these effects took place in companion hepatocytes
      challenged with insulin. By contrast, insulin caused a rapid and sustained
      phosphorylation of protein kinase B, accompanied by a massive induction of the
      mRNA encoding glucokinase. GH had no detectable effect on phosphorylation of
      protein kinase B or level of glucokinase mRNA. Insulin also elicited brief
      hyperphosphorylation of ERK1 and 2, an effect not seen in GH-stimulated
      hepatocytes. Thus, there was a clear demarcation of signaling events triggered in
      hepatocytes by insulin and GH, and this was accompanied by hormone-specific
      responses with respect to the induction of gene expression. Additionally, the
      current results show that signal transducer and activator of transcription 5
      activation is neither necessary nor sufficient for the insulin-dependent
      induction of hepatic glucokinase.

PMID- 12239087
TI  - Thyrotropin, follitropin, and chorionic gonadotropin expressed as a single
      multifunctional unit reveal remarkable permissiveness in receptor-ligand
      interactions.
AB  - The glycoprotein hormones [chorionic gonadotropin (CG), FSH, LH, and TSH] are
      composed of a common alpha-subunit and a hormone-specific beta-subunit. Subunit
      assembly is vital to the in vivo function of these hormones. However, recent in
      vitro studies using double domain (beta-alpha) and triple domain (beta-beta
      alpha) single chains have shown that gonadotropin receptor recognition can
      accommodate conformationally modified ligands. To investigate the extent of
      flexibility of ligand-receptor interactions, we constructed a single chain
      tetramer containing three different beta-subunits (TSHbeta, FSHbeta, and CGbeta)
      and a single alpha-subunit. This analog was inefficiently secreted from
      transfected Chinese hamster ovary cells, but surprisingly, the protein exhibited
      all activities comparable to the corresponding heterodimers. Because the alpha
      subunit presumably cannot form the entire array of heterodimeric contacts with
      all beta-subunits simultaneously in the tetra-domain analog, the data show that
      the complete quaternary subunit-subunit interactions are essential for the
      efficient intracellular trafficking of the glycoprotein hormones, but not for
      receptor recognition. From an evolutionary perspective, the organization of such
      a multifunctional analog is consistent with the hypothesis that glycoprotein
      hormone genes were originally linked in tandem and subsequently evolved as
      independent genes. Our results also indicate that both gonadal and thyroid
      stimulatory functions can be combined in a unique analog.

PMID- 12239088
TI  - Leptin and neuropeptide y have opposing modulatory effects on nucleus of the
      solitary tract neurophysiological responses to gastric loads: implications for
      the control of food intake.
AB  - Leptin is an adiposity hormone that modulates the activity of multiple
      hypothalamic signaling pathways involved in the control of food intake. The
      present experiments were designed to evaluate whether central administration of
      leptin or one of its downstream mediators, neuropeptide Y (NPY), could affect
      food intake by modulating the brain stem neurophysiological response to ascending
      meal-related feedback signals in the nucleus of the solitary tract (NTS) in
      anesthetized male Long-Evans rats. NTS neurons at the rostrocaudal level of the
      area postrema were dose-dependently activated by gastric loads ranging from 2-10
      ml, and leptin and NPY had opposite modulatory effects on this load
      volume/activity relationship: leptin significantly increased NTS responses to
      gastric loads, whereas NPY reduced the potency and efficacy with which gastric
      loads activated NTS neurons. These effects were probably not mediated by
      peripheral effects of centrally administered peptides or by the gastrokinetic
      effects of central NPY or leptin, because the dose-response relationship between
      gastric load volume and neurophysiological firing rate was unchanged in gastric
      load-sensitive vagal afferent fibers. These data suggest a mechanistic framework
      for considering how feeding behavior occurring in meals is altered by challenges
      to energy homeostasis, such as fasting and overfeeding.

PMID- 12239089
TI  - Estrogen receptors alpha and beta have similar activities in multiple endothelial
      cell pathways.
AB  - The presence of both estrogen receptor alpha (ERalpha) and ERbeta in vascular
      cells has greatly increased the complexity of potential estrogen regulatory
      pathways in the cardiovascular system. Here, human umbilical vein endothelial
      cells were engineered using adenovirus vectors to express either ERalpha or
      ERbeta. The activities of ERalpha and ERbeta were compared in three distinct gene
      regulatory pathways, including inhibition of IL-1beta induction of E-selectin
      expression, inhibition of basal endothelin-1 production, and the ability to
      induce two matrix-stabilizing enzymes: tissue transglutaminase and a novel member
      of the lysyl oxidase family. Both ERs were active on these end points, although
      ERbeta was typically less efficacious than ERalpha. As no class of gene
      regulation could differentiate ERalpha from ERbeta activity, we characterized a
      novel steroid (7alpha-thiophenyl-E2) that bound with similar affinities to
      ERalpha and ERbeta, but functioned as an ERalpha agonist and ERbeta antagonist
      for all of these endothelial responses. This pattern of receptor subtype
      selective activity was not unique to endothelial cells, but was also seen in
      metabolically active HepG2 cells, suggesting potential in vivo utility. The panel
      of endothelial responses coupled with a selective modulator should provide a
      means to characterize the roles of ERalpha and ERbeta in endothelial cells in
      vivo.

PMID- 12239090
TI  - Posttranslational modulation of glucocorticoid feedback inhibition at the
      pituitary level.
AB  - Diagnostic tests of hypothalamic-pituitary-adrenocortical function in psychiatric
      illness largely report the interaction of hypothalamic secretagogues with
      glucocorticoids at the pituitary level. This study investigated whether the
      efficiency of glucocorticoid inhibition is subject to modulation by intracellular
      processes that enhance cAMP accumulation and/or facilitate membrane
      depolarization. The secretion of ACTH induced by corticotropin-releasing factor
      (CRF; 0.1 nM) in primary cultures of rat anterior pituitary cells was markedly
      inhibited upon a 2-h exposure to 100 nM corticosterone. Arginine vasopressin (2
      nM) enhanced the cAMP as well as the ACTH responses to CRF and reduced the
      efficiency of glucocorticoid inhibition of ACTH release. The action of arginine
      vasopressin was mimicked by rolipram, an inhibitor of cyclic nucleotide
      phosphodiesterase type 4. Application of the broad specificity K(+) channel
      blockers clofilium and astemizole produced minor or no significant enhancement of
      CRF-induced ACTH release, respectively, but opposed the inhibitory effect of
      corticosterone. Specific blockers of HERG, KCNQ, and Isk channels had no effect
      on ACTH release under any condition examined. In summary, these data reveal
      multiple sites of posttranslational modulation of adrenal corticosteroid action
      at the level of the pituitary gland, which appear important for the outcome of
      diagnostic tests of hypothalamic-pituitary- adrenocortical function.

PMID- 12239092
TI  - Evaluation of neuromedin U actions in energy homeostasis and pituitary function.
AB  - The brain-gut peptide neuromedin U (NMU) has been identified recently as a
      physiological regulator of food intake. To further investigate the central role
      of NMU in energy homeostasis, we examined the distribution of NMU transcript and
      the effect of intracerebroventricular administration on several physiological
      parameters and on the pattern of c-Fos activation. Here we report that
      intracerebroventricular administration of NMU to 24-h fasted rats resulted in a
      decrease in subsequent food intake and body weight gain. NMU administration
      activated neurons in several brain regions implicated in the regulation of
      feeding behavior. Activated cells included catecholaminergic neurons of the
      arcuate nucleus and brain stem. Distribution studies revealed NMU expression in
      the caudal brain stem (nucleus of the solitary tract and inferior olive) and
      pituitary, with significant levels in the pars tuberalis. This contradicts
      earlier published observations. In obese (fa/fa) Zucker rats, decreases in NMU
      expression were detected in the nucleus of the solitary tract, pars tuberalis,
      and pars distalis, whereas in the fasted rat, a decrease in NMU transcript was
      detected in the pars distalis. These results confirm the effects of NMU on
      feeding and suggest additional roles for NMU in neuroendocrine function.

PMID- 12239091
TI  - Activation of phosphatidylinositol 3-kinase contributes to insulin-like growth
      factor I-mediated inhibition of pancreatic beta-cell death.
AB  - To begin to determine whether IGF-I treatment represents a potential means of
      enhancing the survival of islet cell grafts after transplantation, the present
      studies established a model of beta-cell death secondary to loss of trophic
      support and examined the ability of IGF-I to prevent cell death. The studies were
      performed using the rat pancreatic beta-cell line, INS-1. Incubating INS-1 cells
      in RPMI 1640 and 0.25% BSA for 48 h increased cell death, as determined by
      lactate dehydrogenase release, compared with that of cells maintained in RPMI and
      10% fetal calf serum. Addition of 100 ng/ml IGF-I to the serum-free medium
      decreased lactate dehydrogenase release to a level comparable to that found in
      cells maintained in fetal calf serum. Similar results were seen using a mouse
      beta-cell line, MIN6, infected with an adenovirus expressing IGF-I. Examination
      of IGF-I-stimulated signaling demonstrated that IGF-I increased the
      phosphorylation of protein kinase B in both cell lines, whereas IGF-I-induced
      phosphorylation of the MAPKs, ERK1 and -2, was observed only in INS-1 cells. The
      effect of IGF-I on phosphorylation of substrates of phosphatidylinositol 3-kinase
      (PI 3-kinase) or protein kinase B was also examined in INS-1 cells. IGF-I
      increased the phosphorylation of glycogen synthase kinase 3beta, BAD, FKHR, and
      p70(S6) kinase. Another pathway that has been shown to mediate the protective of
      IGF-I in some cell types is activation of cAMP response element-binding protein
      (CREB). IGF-I increased CREB phosphorylation at a concentration as low as 10
      ng/ml, and this effect was inhibited by H89, a PKA inhibitor, and PD98059, a MAPK
      kinase inhibitor. Consistent with the effect of IGF-I on CREB phosphorylation,
      IGF-I increased the transcriptional activity of CREB, although it had no effect
      on CREB binding to DNA. Use of inhibitors of the PI 3-kinase (LY 294002) or ERK
      (PD98059) pathways or CREB phosphorylation (H89) in the cell death assay
      demonstrated partial abrogation of the protective effect of IGF-I with LY 294002.
      These data demonstrate that IGF-I protects pancreatic beta-cells from cell death
      secondary to loss of trophic support and that, although IGF-I activates several
      signaling pathways that contribute to its protective effect in other cell types,
      only activation of PI 3-kinase contributes to this effect in beta-cells.

PMID- 12239093
TI  - Identification and characterization of a selective, nonpeptide follicle
      stimulating hormone receptor antagonist.
AB  - The glycoprotein hormones (LH, FSH, and TSH) are critical to the maintenance of
      physiological homeostasis and control of reproduction. However, despite an
      obvious utility for synthetic pharmacological agents, there are few reports of
      selective, nonpeptide agonists or antagonists to receptors for these hormones. We
      have identified and characterized a novel synthetic molecule capable of
      inhibiting the action of FSH. This compound, 7-[4-[Bis-(2-carbamoyl-ethyl)-amino]
      6-chloro-(1,3,5)-triazin-2-ylamino)-4-hydroxy-3-(4-methoxy-phenylazo)
      naphthalene]-2-sulfonic acid, sodium salt (compound 1), is a selective,
      noncompetitive inhibitor of the human (h) and rat (r) FSH receptors (FSHRs).
      Compound 1 selectively inhibited binding of [(125)I]hFSH with an IC(50) value of
      5.4 +/- 2.3 micro M. Radioligand-binding assays were performed using the
      baculovirus expressed extracellular domain of hFSHR (BV-tFSHR) to demonstrate
      site-specific interaction. Compound 1 competed for [(125)I]hFSH binding to BV
      tFSHR with an IC(50) value of 10 +/- 2.8 micro M. Functionally, compound 1
      inhibited hFSH-induced cAMP accumulation and steroidogenesis in vitro with an
      IC(50) value of 3 +/- 0.6 micro M. Competition of compound 1 for binding to other
      glycoprotein hormone receptors and other G protein-coupled receptors demonstrated
      select activity for FHSRs. Compound 1 inhibited ovulation in immature and cycling
      adult rats. These data provide proof of concept that selective, small molecule
      antagonists can be designed for glycoprotein hormone receptors.

PMID- 12239094
TI  - Calcium-sensing receptor activation of rho involves filamin and rho-guanine
      nucleotide exchange factor.
AB  - We investigated the role of Galphaq, filamin, Rho, the RhoGEF Lbc, and the C
      terminus of calcium-sensing receptor (CasR) in CasR signaling. We found that
      Ca(2+), Mg(2+), or the calcimimetic R isomer of N-(3-[2-chlorophenyl]propyl)-(R)
      alpha-methyl-3-methoxybenzylamine (NPS-R568) stimulated serum response element
      (SRE) activity human embryonic kidney 293 cells transfected with CasR and an SRE
      luciferase reporter construct. Coexpression of either the dominant negative
      Galphaq(305-359) minigene, regulators of G protein signaling (RGS)2 or RGS4,
      inhibited CasR-stimulated SRE activity, consistent with CasR activation of
      Galphaq. The cytoskeletal associated Rho protein is involved CasR activation of
      SRE, as evidenced by CasR-mediated increase in membrane-associated Rho A and by
      the ability of Clostridium botulinum C3 (C3) exoenzyme to inhibit both CasR and
      GalphaqQL-stimulated SRE activity. Overexpression of the RhoGEF Lbc, lacking
      either the Dbl-homology or Pleckstrin homology domain, as well as the filamin
      peptide (1530-1875) inhibited CasR-mediated activation of SRE. A carboxyl
      terminal CasR minigene, CasR(906-980), encoding a filamin binding region, also
      blocked CasR- and GalphaqQL-stimulated SRE activity. Potential interactions
      between CasR, RhoGEF Lbc, Rho A, Galphaq, and filamin were demonstrated by
      reciprocal coimmunoprecipitation studies. Our results suggest that the C terminus
      of CasR may interact with filamin to create a cytoskeletal scaffold necessary for
      the spatial organization of Galphaq, RhoGEF Lbc, and Rho signaling pathways
      upstream of SRE activation.

PMID- 12239095
TI  - Effect of proinflammatory cytokines on gene expression of the diabetes-associated
      autoantigen IA-2 in INS-1 cells.
AB  - Cytokines released from activated antigen-presenting cells and T-lymphocytes are
      crucially involved in the pathogenesis of type 1 diabetes. Previous studies have
      shown that proinflammatory cytokines play an important role in the induction of
      autoimmunity and beta-cell damage. Inhibition of insulin expression has been
      described, but their effects on other major target autoantigens, such as the
      tyrosine phosphatase-like protein IA-2, is not known. In the present study, we
      established sensitive real-time RT-PCR to measure IA-2, insulin, and inducible
      nitric oxide (NO) synthase (iNOS) mRNA expression. Rat insulinoma INS-1 cells
      were stimulated with IL-1beta, TNF-alpha, interferon (IFN)-gamma, and IL-2 as
      well as with two combinations of these cytokines (C1: IL-1beta + TNF-alpha + IFN
      gamma; C2: TNF-alpha + IFN-gamma). Treatment with IL-1beta, TNF-alpha, or IFN
      gamma alone caused a significant down-regulation of IA-2 and insulin mRNA levels
      in a time and dose-dependent manner, whereas IL-2 had no effect. Exposure to
      cytokine combinations strongly potentiates the inhibitory effects. Incubation of
      cells with C1 and C2 for 24 h induces a significant inhibition of IA-2 mRNA
      levels by 78% and 58%, respectively. Under these conditions, an up to 5 x 10(4)
      fold increase of iNOS gene expression was observed. The hypothesis that the
      formation of NO is involved in IA-2 regulation was confirmed by the finding that
      the coincubation of C1 with 4 mM L-N(G)-monomethyL-L-arginine, an inhibitor of
      the iNOS, partly reversed the down-regulation of IA-2. Further, incubation with
      the synthetic NO-donor S-nitroso-N-acetyl-D-L-penicillamine significantly
      decreased IA-2 mRNA level to 51% of basal levels. In conclusion, we have
      demonstrated for the first time that IL-1beta, TNF-alpha, and IFN-gamma exert a
      strong inhibitory effect on expression of the diabetes autoantigen IA-2. The
      action of IL-1beta may be partly mediated by the activation of the NO pathway.

PMID- 12239096
TI  - Agouti-related protein (AGRP) has a central inhibitory action on the hypothalamic
      pituitary-thyroid (HPT) axis; comparisons between the effect of AGRP and
      neuropeptide Y on energy homeostasis and the HPT axis.
AB  - Because alpha-MSH has a potent stimulatory action on hypophysiotropic TRH
      synthesizing neurons in the hypothalamic paraventricular nucleus (PVN),
      preventing the effects of fasting on the gene expression of the TRH prohormone
      (proTRH), we hypothesized that agouti-related protein (AGRP), a melanocortin
      receptor antagonist, may exert a central inhibitory action on these neurons. To
      test the hypothesis, the effects of intracerebroventricularly administered AGRP
      on circulating thyroid hormone levels and proTRH mRNA in the hypothalamic
      paraventricular nucleus (PVN) were compared with the effects of the recently
      described central inhibitor of the HPT axis, neuropeptide Y (NPY). AGRP
      administration increased food consumption and weight gain, suppressed circulating
      levels of thyroid hormones (T(3) and T(4)), and resulted in an inappropriately
      normal TSH. These alterations were associated with a significant suppression of
      proTRH mRNA in the PVN, indicating that AGRP infusion resulted in a state of
      central hypothyroidism. While similar observations were made in the NPY-infused
      animals, AGRP-treated animals had higher feeding efficiency, higher T(4) levels,
      and lower type 2 iodothyronine deiodinase levels in brown adipose tissue than NPY
      infused animals. These data demonstrate that AGRP and NPY have a similarly potent
      inhibitory action on the proTRH gene expression of hypophysiotropic neurons,
      indicating that both AGRP and NPY may play a major role in the inhibition of the
      HPT axis during fasting.

PMID- 12239097
TI  - Dual regulation of the parathyroid hormone (PTH)/PTH-related peptide receptor
      signaling by protein kinase C and beta-arrestins.
AB  - We examined here the role of second messenger-dependent kinases and beta
      arrestins in short-term regulation of the PTH receptor (PTHR) signaling. The
      inhibition of protein kinase C (PKC) in COS-7 cells transiently expressing PTHR,
      led to an approximately 2-fold increase in PTH-stimulated inositol phosphate (IP)
      and cAMP production. The inhibition of protein kinase A increased cAMP production
      1.5-fold without affecting IP signaling. The effects of PKC inhibition on PTHR
      mediated G(q) signaling were strongly decreased for a carboxy-terminally
      truncated PTHR (T480) that is phosphorylation deficient. PKC inhibition was
      associated with a decrease in agonist-stimulated PTHR phosphorylation and
      internalization without blocking PTH-dependent mobilization of beta-arrestin2 to
      the plasma membrane. Overexpression of beta-arrestins strongly decreased the PTHR
      mediated IP signal, whereas cAMP production was impaired to a much lower extent.
      The regulation of PTH-stimulated signals by beta-arrestins was impaired for the
      truncated T480 receptor. Our data reveal mechanisms at, and distal to, the
      receptor regulating PTHR-mediated signaling pathways by second messenger
      dependent kinases. We conclude that regulation of PTHR-mediated signaling by PKC
      and beta-arrestins are separable phenomena that both involve the carboxy terminus
      of the receptor. A major role for PKC and beta-arrestins in preferential
      regulation of PTHR-mediated G(q) signaling by independent mechanisms at the
      receptor level was established.

PMID- 12239098
TI  - Dexamethasone and tumor necrosis factor-alpha act together to induce the cellular
      inhibitor of apoptosis-2 gene and prevent apoptosis in a variety of cell types.
AB  - Using microarray technology, we analyzed 12,000 genes for regulation by TNF-alpha
      and the synthetic glucocorticoid, dexamethasone, in the human lung epithelial
      cell line, A549. Only one gene was induced by both agents, the cellular inhibitor
      of apoptosis 2 (c-IAP2), which was induced 17-fold and 5-fold by TNF-alpha at 2 h
      and 24 h, respectively, and increased 14-fold and 9-fold by dexamethasone at 2 h
      and 24 h, respectively. The combination of the two agents together led to an
      additive increase (34-fold) at 2 h and a more than additive effect (36-fold) at
      24 h. The human c-IAP2 promoter contains two nuclear factor (NF)-kappaB sites
      that have been shown to be required for transcriptional activation by TNF-alpha.
      To test whether glucocorticoids regulate the c-IAP2 gene at the level of the
      promoter, a reporter vector containing 947 bases upstream of the start site of
      transcription of the human c-IAP2 promoter was linked to luciferase [IAP(-947
      +54)-LUC] and transfected into A549 cells. Dexamethasone and TNF-alpha each
      induced reporter activity, whereas the combination of the two agents led to
      greater induction of luciferase than either one alone. Truncation of the promoter
      region containing a putative glucocorticoid response element (GRE) at -515 [IAP(
      395-+54)-LUC] or mutation of the GRE in the context of the natural promoter [IAP(
      947-+54mutGRE)-LUC] resulted in a loss of dexamethasone-mediated induction of
      reporter activity. Although the functional NF-kappaB sites were retained in the
      truncated and mutant c-IAP2 promoter constructs, dexamethasone did not inhibit
      the TNF-alpha induction of luciferase activity, indicating that GR repression
      through the NF-kappaB sites did not occur. Regulation of the c-IAP2 gene is
      therefore unique, as GR and NF-kappaB signaling pathways are usually mutually
      antagonistic, not cooperative. Treatment of A549 cells with TNF-alpha and/or
      dexamethasone had no effect on cell death, but the two agents were able to
      inhibit interferon-gamma/anti-FAS antibody-mediated apoptosis. In human
      glioblastoma A172 cells, TNF-alpha and dexamethasone together elicited a greater
      than additive increase in c-IAP2 mRNA levels and also inhibited anti-FAS antibody
      mediated A172 cell apoptosis. In contrast, in human CEM-C7 leukemic T cells,
      whereas TNF-alpha and dexamethasone treatment also led to an increase in c-IAP2
      mRNA, the two agents were able to induce apoptosis on their own. However, TNF
      alpha and dexamethasone were also able to blunt anti-FAS-induced apoptosis in the
      T cells. These data indicate that the induction of the antiapoptotic protein, c
      IAP2, by glucocorticoids and TNF-alpha correlates with the ability of these
      agents to inhibit apoptosis in a variety of cell types.

PMID- 12239099
TI  - Strain-dependent stimulation of growth in leptin-treated obese db/db mice.
AB  - Leptin increases the proliferation of various cell types in vitro, and we
      reported that background strain influences the metabolic responses to leptin in
      db/db mice, which express short-form, but not long-form, leptin receptors. Here,
      we examined the effects of leptin on growth of young C57BL/Ks, C57BL/6J, and
      C57BL/3J db/db mice. Intraperitoneal infusions of 20 micro g leptin/d for 26 d
      increased the food intake of C57BL/6J mice by 15% (P < 0.01), but had no effect
      in C57BL/Ks db/db mice. Leptin-infused C57BL/6J db/db mice gained more weight (
      approximately 20%; P < 0.04) than PBS-infused controls. The increased weight was
      sustained after leptin infusion ended. Leptin had no effect on weight gain or
      food intake of C57BL/3J db/db mice, which only express the soluble leptin
      receptor. A single leptin injection increased MAPK phosphorylation in liver by
      40% (P < 0.001) and that in muscle tissues by 20% (P < 0.001) in C57BL/6J mice,
      but did not change phosphorylation in C57BL/3J db/db mice. These results suggest
      that leptin increases the weight gain of C57BL/6J db/db mice by activating the
      MAPK pathway through a mechanism that is dependent on short-form leptin
      receptors. This response may be masked by activation of the long-form receptor in
      wild-type animals that lose body fat during leptin treatment.

PMID- 12239100
TI  - Rottlerin inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes by
      uncoupling mitochondrial oxidative phosphorylation.
AB  - There is increasing evidence that protein kinase C (PKC) isoforms modulate
      insulin-signaling pathways in both positive and negative ways. Recent reports
      have indicated that the novel PKCdelta mediates some of insulin's actions in
      muscle and liver cells. Many studies use the specific inhibitor rottlerin to
      demonstrate the involvement of PKCdelta. In this study, we investigated whether
      PKCdelta might play a role in 3T3-L1 adipocytes. We found that PKCdelta is highly
      expressed in mouse adipose tissue and increased on 3T3-L1 adipocyte
      differentiation, and insulin-stimulated glucose transport is blocked by
      rottlerin. The phosphorylation state and activity of PKCdelta are not altered by
      insulin, but the protein translocates to membranes following insulin treatment.
      In contrast to the results with rottlerin, inhibition of PKCdelta activity or
      expression has no effect on glucose transport in adipocytes, unlike muscle cells.
      Lastly, we found that rottlerin lowers adenosine triphosphate levels in 3T3-L1
      cells by acting as a mitochondrial uncoupler, and this is responsible for the
      observed inhibition of glucose transport.

PMID- 12239101
TI  - Androgen modulation of adhesion and antiadhesion molecules in PC-3 prostate
      cancer cells expressing androgen receptor.
AB  - The metastatic spread of cancer cells involves a complex process of detachment
      via antiadhesion molecules and attachment and migration through adhesion. In the
      prostate, androgens are generally thought to contribute to the development and
      progression of prostate cancer by promoting cell proliferation and survival
      through poorly defined mechanisms. We have reported previously that PC-3 prostate
      cancer cells, which are unresponsive to androgens, show androgen-dependent
      detachment and ultimately apoptosis when stably transfected with a full-length
      human androgen receptor (AR) cDNA. We now demonstrate that treatment of these
      cells with 5alpha-dihydrotestosterone (DHT) for 24 or 48 h increased the
      expression of antiadhesion mucin MUC-1 at the cell surface as detected by flow
      cytometry with two independent antibodies. This increase in protein was
      concordant with up-regulation of MUC-1 mRNA in the AR-transfected PC-3 sublines,
      as determined by quantitative RT-PCR. Treatment with DHT for 48 h also down
      regulated the cell surface expression of alpha2beta1-integrin but having little
      effect on the levels of alpha3beta1- and alpha5beta1-integrins. Androgen also
      decreased, in a dose-dependent manner, the adhesion of AR-transfected PC-3 cells
      to collagen type I, which was shown to be specifically inhibited by blocking
      antibody to alpha2beta1-integrin. The present data demonstrate that DHT can
      modulate expression of adhesion and antiadhesion molecules and suggest that this
      effect of androgen might contribute to prostate cancer progression.

PMID- 12239102
TI  - Diurnal rhythm of agouti-related protein and its relation to corticosterone and
      food intake.
AB  - In the present study we examined the diurnal patterns of agouti-related protein
      (AGRP) and proopiomelanocortin (POMC) mRNA expression in the arcuate nucleus and
      their relation to circulating glucocorticoids and food intake. Animals were
      killed at 4-h intervals throughout the 24-h diurnal cycle, and the expression of
      AGRP and POMC mRNA was evaluated by semiquantitative in situ hybridization
      analysis. We observed a significant diurnal rhythm in AGRP mRNA expression, with
      a marked peak at 2200 h (4 h after lights off) and a trough at 1000 h (4 h after
      lights on), consistent with the overall day-night rhythm of food intake. In
      contrast, POMC mRNA levels did not show a significant fluctuation across the
      diurnal cycle, although there was a tendency for levels to decrease after the
      onset of the dark cycle. Corticosterone secretion temporally coincided with the
      rising phase of AGRP mRNA expression. Depletion of corticosterone by
      adrenalectomy abolished the AGRP diurnal rhythm by suppressing the nighttime
      expression, but did not alter the feeding rhythm. Exposure of adrenalectomized
      rats to constant corticosterone replacement (10 or 50 mg continuous release
      corticosterone pellet) resulted in fixed AGRP mRNA expression throughout the 12-h
      light, 12-h dark cycle. A relatively high level of corticosterone (50 mg)
      significantly increased AGRP mRNA expression, with a positive correlation between
      these two measures. These results indicate that 1) the diurnal expression of AGRP
      mRNA is regulated by corticosterone independently of the light/dark cue; and 2) a
      normal endogenous corticosterone rhythm is required for generating the diurnal
      AGRP rhythm.

PMID- 12239103
TI  - Different mechanisms for leukemia inhibitory factor-dependent activation of two
      proopiomelanocortin promoter regions.
AB  - To better understand how leukemia inhibitory factor (LIF) activates
      proopiomelanocortin (POMC) gene transcription in pituitary corticotrophs, time
      course studies of the induction of POMC promoter activity and specific tyrosine
      phosphorylation of signal transducer and activator of transcription 1 (STAT1) and
      STAT3 were performed. It was found that both phosphorylation of STAT1 and -3 and
      activation of the promoter activity rapidly and transiently take place within
      minutes and 2-6 h, respectively, in favor of a direct effect of the LIF pathway
      on POMC promoter. Activated STAT1 and -3 form homo-/heterodimers able to bind the
      Sis-inducible element. The most abundant Sis-inducible element binding dimers are
      STAT3/3 and STAT1/3. Degenerated STAT1/3-binding sites from the POMC promoter
      were tested for their ability to bind activated STAT1 and 3; only the -390/-379
      site, partially overlapping the Nur response element, binds with low affinity
      activated STAT1 and -3. Analysis of the three domains and subregions of the POMC
      promoter showed that two subregions are specifically responsive to LIF. The
      response of the distal subregion requires the intact STAT1 and -3 DNA-binding
      site -390/-379, whereas the responsiveness of the proximal subregion takes place
      despite the absence of direct STAT1 and -3 DNA binding and may imply interaction
      of activated STAT with basal transcription factors.

PMID- 12239104
TI  - Ovarian stanniocalcin is structurally unique in mammals and its production and
      release are regulated through the luteinizing hormone receptor.
AB  - Stanniocalcin (STC) is a recently discovered mammalian hormone that is widely
      distributed in many tissues. In rodents the STC gene is most highly expressed in
      ovary, specifically in androgen-producing thecal and interstitial cells. In
      addition, ovarian levels of expression rise 15-fold over pregnancy. The objective
      of this study was to develop a primary culture system for ovarian thecal
      interstitial cells (TICs) to identify factors governing STC production and
      release. We used highly purified primary cultures of rat and bovine TICs, the
      purity of which was routinely assessed with antigenic and enzymatic markers. The
      functionality of cells was assured by their responsiveness to LH in the form of
      progesterone release. We found that forskolin significantly increased STC gene
      expression and secretion by both rat and bovine TICs, an effect that was only
      replicated by human (h) chorionic gonadotropin (CG). Coincubation of TICs with
      hCG and phosphodiesterase inhibitors further increased STC secretion, whereas
      coincubation of TICs with hCG and protein kinase A inhibitors attenuated hCG
      stimulated release. Intriguingly, ovarian STC proved to be substantially larger
      than the 50-kDa homodimer produced in most other tissues. These results indicate
      that ovarian STC is physically distinct, a feature that could explain its
      presence in serum during pregnancy and lactation.

PMID- 12239105
TI  - Protein kinase A-dependent cooperation between GATA and CCAAT/enhancer-binding
      protein transcription factors regulates steroidogenic acute regulatory protein
      promoter activity.
AB  - Steroidogenic acute regulatory protein (StAR) is an essential cholesterol
      transporter in steroidogenic tissues. Hormone-induced StAR expression is
      regulated through the cAMP-dependent pathway involving activation of protein
      kinase A (PKA). The StAR promoter contains several conserved DNA regulatory
      elements. These include binding sites for steroidogenic factor 1, CCAAT/enhancer
      binding protein (C/EBP), and GATA transcription factors. Although these elements
      are important for StAR promoter activity, how the various transcription factors
      that bind these elements cooperate to confer cAMP responsiveness remains poorly
      understood. As induction of StAR transcription by cAMP in steroidogenic MA-10
      cells does not require de novo protein synthesis, this suggests that all
      essential transcription factors are present and that posttranslational
      modifications of the factors are involved. We now report that GATA-4 is
      phosphorylated in MA-10 cells in response to cAMP and in heterologous CV-1 cells,
      GATA-4 transcriptional activity is stimulated by PKA. Moreover, we show that GATA
      4 and C/EBPbeta directly interact in vitro and in vivo and synergistically
      activate the StAR promoter in CV-1 cells exclusively in the presence of PKA. As
      PKA-dependent synergy was also observed with other GATA and C/EBP family members,
      this transcriptional cooperation may contribute to hormone-stimulated StAR
      expression in all steroidogenic tissues.

PMID- 12239106
TI  - Temperature-sensitive phenotype in mice lacking pituitary adenylate cyclase
      activating polypeptide.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved
      hormone. Targeted disruption of the PACAP gene has revealed a role for this
      peptide in lipid metabolism, carbohydrate metabolism, and the sympathetic
      response to insulin stress. We report here that PACAP null mice are temperature
      sensitive. When raised at 21 C, only 11% of the PACAP null mice survived past the
      first 2 wk after birth, but when raised at 24 C, most (76%) of the PACAP null
      mice survived. The question is the mechanism by which the absence of PACAP
      affects thermoregulation. Brown adipose tissue is the major site of adaptive
      thermogenesis in neonates and rodents. We show that PACAP null mice have brown
      adipocytes that differentiate normally and express two enzymes involved in
      thermogenesis, hormone-sensitive lipase and uncoupling protein 1. Likewise,
      levels of catecholamines in the adrenal medulla and plasma are normal in PACAP
      null mice raised at a lower temperature. In contrast, norepinephrine and its
      precursor dopamine extracted from brown adipose tissue are present at
      significantly lower levels in the PACAP null mice compared with controls. Also,
      PACAP null mice showed a greater loss of core body temperature compared with wild
      type controls at 21 C. We conclude that under prolonged but mild cold stress,
      lack of PACAP results in inadequate heat production due to insufficient
      norepinephrine stimulation of brown adipose tissue.

PMID- 12239107
TI  - Transgenic mice overexpressing insulin-like growth factor binding protein-5
      display transiently decreased osteoblastic function and osteopenia.
AB  - Skeletal cells synthesize IGFs and their six IGF binding proteins (IGFBP). IGFBP
      5 was reported to stimulate bone cell growth in vitro and selected parameters of
      osteoblastic function in vivo, but its actual effects on bone formation are not
      established. We investigated the direct effects of IGFBP-5 on bone remodeling in
      two lines of transgenic mice overexpressing IGFBP-5 under the control of the
      osteocalcin promoter. Static and dynamic histomorphometry revealed that IGFBP-5
      transgenic mice had a transient decrease in trabecular bone volume secondary to
      reduced trabecular number and thickness and a transient decrease in bone mineral
      apposition rate. Osteoblast number was normal, indicating impaired osteoblastic
      function. Osteoclast number and bone resorption were normal. Total, vertebral,
      and femoral bone mineral densities were reduced in IGFBP-5 transgenics by 14-27%
      at 4 wk of age, but not in older animals. Stromal cells expressing the IGFBP-5
      transgene displayed decreased expression of alkaline phosphatase, osteocalcin,
      core binding factor 1, and type I collagen transcripts when compared with cells
      from wild-type animals. In conclusion, transgenic mice overexpressing IGFBP-5 in
      the bone microenvironment have a transient decrease in trabecular bone volume,
      impaired osteoblastic function, and osteopenia.

PMID- 12239108
TI  - Friend of GATA (FOG)-1 and FOG-2 differentially repress the GATA-dependent
      activity of multiple gonadal promoters.
AB  - The GATA transcription factors are crucial regulators of cell-specific gene
      expression in many tissues. GATA proteins are abundantly expressed in gonads of
      several species. In vertebrates, GATA factors are expressed from the onset of
      gonadal development and are later found in multiple cell lineages of both the
      testis and ovary. GATA factors activate transcription of several gonadal genes
      including the hormone-encoding genes Mullerian inhibiting substance (MIS) and
      inhibin alpha and genes involved in steroidogenesis like P450 aromatase (Cyp 19)
      and steroidogenic acute regulatory protein. GATA factors also contribute to cell
      specific gonadal gene expression through cooperative interactions with other
      transcription factors such as the orphan nuclear receptor steroidogenic factor-1.
      GATA transcriptional activity is also modulated by two multitype zinc finger
      proteins called the Friend of GATA (FOG) proteins, which were cloned as GATA
      specific cofactors. The FOG proteins (FOG-1 and FOG-2) can act as either
      enhancers or repressors of GATA transcriptional activity, depending on the cell
      and promoter context. We now report that the FOG proteins are coexpressed with
      GATA factors in testicular cells in which they differentially repress the
      promoter activities of several GATA-dependent target genes. These findings
      implicate the FOG proteins in the regulation of GATA-dependent gene transcription
      in the gonads.

PMID- 12239109
TI  - Expression of estrogen receptor-alpha and cFos in norepinephrine and epinephrine
      neurons of young and middle-aged rats during the steroid-induced luteinizing
      hormone surge.
AB  - Norepinephrine (NE) and epinephrine are important stimulators of GnRH release
      during the preovulatory surge in female rats. Previous studies have shown that
      the catecholaminergic neurons are sensitive to estradiol and that NE release in
      the hypothalamus is decreased in middle-aged rats at the time when the estrous
      cycles become irregular and later cease to exist. The aims of the present study
      were to determine whether the NE and epinephrine neurons continue to express
      estrogen receptor (ER)-alpha in middle-aged rats; temporal expression of ER-alpha
      and cFos changes with age during the steroid-induced surge; and tyrosine
      hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanol-N
      methyltransferase mRNA content in catecholaminergic neurons of the brain stem
      changes during the surge with age. The results show that there was no difference
      in TH mRNA content; however, DBH mRNA levels in areas A1, A2, and C1 of the
      middle-aged animals did not rise during the surge as was observed in the young
      animals. Although the percentage of NE and epinephrine neurons that express ER
      alpha was unchanged during the surge in both young and middle-aged animals, cFos
      expression was enhanced in areas A1 and A2 of the middle-aged animals but not in
      the young animals. Together the results suggest that NE and epinephrine neurons
      in the middle-aged rat continue to express appropriate basal levels of TH, DBH,
      and phenylethanol-N-methyltransferase mRNAs as well as ER-alpha and cFos;
      however, the enhancement of DBH expression, as seen in the young animals during
      the steroid-induced surge, was not detected in middle-aged animals. On the other
      hand, cFos expression in the middle-aged rat was higher in areas A1 and A2 during
      the surge. It is concluded that the reduced catecholamine release during the
      surge in middle-aged rats is caused, in part, by an altered sensitivity of the NE
      neurons to estradiol, which results in an aberrant cFos expression and probably
      not by major deficits in the expression of transmitter synthesizing enzymes or
      steroid receptors.

PMID- 12239110
TI  - A prostaglandin f(2alpha) analog induces suppressors of cytokine signaling-3
      expression in the corpus luteum of the pregnant rat: a potential new mechanism in
      luteolysis.
AB  - PRL and placental lactogen (PL) play key roles in maintaining the rodent corpus
      luteum through pregnancy. Suppressors of cytokine signaling (SOCS) have been
      shown to decrease cell sensitivity to cytokines, including PRL, and so here we
      have addressed the issue of whether luteolysis induced by prostaglandin F(2alpha)
      (PGF(2alpha)) might up-regulate SOCS proteins to inhibit PRL signaling. In d 19
      pregnant rats, cloprostenol, a PGF(2alpha) analog, rapidly induced transcripts
      for SOCS-3 and, to a lesser extent, SOCS-1. We also found increased SOCS-3
      protein in the ovary by immunoblot and in the corpus luteum by
      immunohistochemistry. Increased SOCS-3 expression was preceded by an increase in
      STAT3 tyrosine phosphorylation 10 min after cloprostenol injection and was
      maintained for 4 h, as determined by gel shift and immunohistochemistry.
      Induction of SOCS-3 was accompanied by a sharp decrease in active STAT5, as
      determined by gel-shift assay and by loss of nuclear localized STAT5. Four hours
      after cloprostenol administration, the corpus luteum was refractory to
      stimulation of STAT5 by PRL administration, and this was not due to down
      regulation of PRL receptor. Therefore, induction of SOCS-3 by PGF(2alpha) may be
      an important element in the initiation of luteolysis via rapid suppression of
      luteotropic support from PL.

PMID- 12239111
TI  - Vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating peptide
      receptor 2 deficiency in mice results in growth retardation and increased basal
      metabolic rate.
AB  - Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase
      activating peptide (PACAP) are two closely related peptides that bind two
      homologous G protein-coupled receptors, VIP/PACAP receptor 1 (VPAC1R) and
      VIP/PACAP receptor II (VPAC2R), with equally high affinity. Recent reports
      suggest that VPAC2R plays a role in circadian rhythm and T cell functions. To
      further elucidate the functional activities of VPAC2R, we generated VPAC2R
      deficient mice by deleting exons VIII-X of the VPAC2R gene. The VPAC2R-deficient
      mice showed retarded growth and had reduced serum IGF-I levels compared with
      gender-matched, wild-type siblings. The mutant mice appeared healthy and fertile
      at a young adult age. However, older male mutant mice exhibited diffuse
      seminiferous tubular degeneration with hypospermia and reduced fertility rate.
      The mutant mice appeared to have an increase in insulin sensitivity. VPAC2R
      deficient mice had increased lean mass and decreased fat mass with reduced serum
      leptin levels. Indirect calorimetry experiments showed that the respiratory
      quotient values immediately following the transition into the dark cycle were
      significantly higher in male knockout mice for about 4 h. Additionally, male and
      female VPAC2R-deficient mice presented an increased basal metabolic rate (23% and
      10%, respectively) compared with their wild-type siblings. Our results suggest
      that VPAC2R plays an important role in growth, basal energy expenditure, and male
      reproductive functions.

PMID- 12239112
TI  - Expression of vascular endothelial growth/permeability factor by endometrial
      glandular epithelial and stromal cells in baboons during the menstrual cycle and
      after ovariectomy.
AB  - Vascular endothelial growth/permeability factor (VEG/PF) has a crucial role in
      angiogenesis, and neovascularization is essential in preparing the uterine
      endometrium for implantation. However, the regulation of VEG/PF synthesis by
      particular cell types of the endometrium during the human menstrual cycle is not
      well understood. Therefore, in the present study the baboon was used as a
      nonhuman primate to determine the role of the ovary in vivo in endometrial VEG/PF
      expression. VEG/PF mRNA levels were quantified by competitive RT-PCR in whole
      uterine endometrium and in glandular epithelial and stromal cells isolated from
      the endometrium by laser capture microdissection of baboons during the normal
      menstrual cycle and after ovariectomy, which decreased serum estradiol and
      progesterone to undetectable levels. Mean (+/-SE) levels (attomoles per
      micrograms of total RNA) of the 323-bp VEG/PF mRNA product, which reflected
      collective expression of all VEG/PF isoforms, in whole endometrium were 785 and
      727 +/- 158 during the mid and late follicular phases, respectively, and 1108 +/-
      320 during the midcycle surge in serum estradiol. VEG/PF mRNA levels then
      declined briefly before increasing to 1029 +/- 365 attomoles/ micro g RNA during
      the late luteal phase of the menstrual cycle. VEG/PF mRNA levels (attomoles per
      femtomole of 18S rRNA) were similar in glandular epithelial (2.27 +/- 1.11) and
      stromal (2.54 +/- 0.70) cells at the midcycle estradiol peak and the midluteal
      phase of the menstrual cycle (2.34 +/- 1.30 and 1.49 +/- 0.53, respectively).
      Immunocytochemical expression of VEG/PF protein was abundant in glandular and
      luminal epithelium, stroma, and vascular endothelium. Endometrial vessel density
      and percent vascularized area, determined by morphometric image analysis, were
      similar during the various stages of the baboon menstrual cycle. After
      ovariectomy, VEG/PF mRNA levels (attomoles per femtomole of 18S rRNA) in the
      endometrial glands (0.52 +/- 0.21) and stroma (0.22 +/- 0.11) were decreased to
      values that were approximately 20% and 10% (P < 0.05), respectively, of those in
      intact baboons during the midcycle estrogen surge. Moreover, there was relatively
      little VEG/PF protein immunostaining in the endometrial glands, stroma, and
      vascular endothelium after ovariectomy. In summary, VEG/PF mRNA and protein
      expression in glandular epithelial and stromal cells were markedly suppressed
      after ovariectomy, indicating that synthesis of this angiogenic factor in these
      endometrial cells is dependent upon a product(s) secreted by the ovary. Moreover,
      endometrial VEG/PF expression remained relatively constant and thus was available
      as a component of the angiogenic system throughout the menstrual cycle,
      presumably to progressively promote vascular reconstruction of the endometrium.

PMID- 12239113
TI  - Antitumorigenic and antiinsulinogenic effects of calcitriol on insulinoma cells
      and solid beta-cell tumors.
AB  - Malignant insulinoma is a rare form of cancer with a poor prognosis because of
      metastatic dissemination and untreatable hypoglycemia. Effective chemotherapy of
      patients who are not cured by surgery is needed. Calcitriol has known anticancer
      properties on different neoplastic cell lines, but no data are available
      regarding its activity on tumorigenic pancreatic beta-cells. We analyzed the in
      vitro effects of calcitriol on the murine insulinoma cell line betaTC(3) and
      primary cultures of human isolated islets and benign insulinoma. The effect of in
      vivo calcitriol administration on insulinoma of recombinant insulin/Simian virus
      40 oncogene-expressing transgenic mice was also investigated. In betaTC(3),
      calcitriol induced growth inhibition; apoptosis; down-regulation of insulin gene
      expression; and nongenomic activation of the MAPK pathway. MAPK kinase inhibitor
      (UO126) and staurosporine reduced calcitriol-mediated betaTC(3) death, and down
      regulation of insulin gene transcription was prevented by staurosporine but not
      UO126. Calcitriol significantly decreased insulin release and mRNA levels of
      human islets and insulinoma cells. Finally, recombinant insulin/Simian virus 40
      oncogene-expressing transgenic mice treated with calcitriol showed reduced
      insulinoma volumes because of increased apoptosis of adenomatous cells. Together,
      these findings provide the rationale for testing the efficacy of calcitriol in
      the treatment of patients with solid beta-cell tumors.

PMID- 12239114
TI  - A polymorphic form of steroidogenic factor-1 is associated with
      adrenocorticotropin resistance in y1 mouse adrenocortical tumor cell mutants.
AB  - ACTH resistance in mutant derivatives of the Y1 mouse adrenocortical tumor cell
      line results from a defect that affects the activity of steroidogenic factor-1
      (SF1), thereby preventing the expression of the melanocortin-2 receptor. In this
      report, we show that the SF1 genes in ACTH-resistant mutants differ from the gene
      in ACTH-responsive Y1 cells by two base changes-one that changes an Ala to Ser at
      codon 172, and one in the third position of codon 3 that does not affect the
      protein sequence. Furthermore, several of the mutants contain multiple copies of
      this alternate SF1 gene (SF1(S172)) on acentric chromosome fragments. The
      SF1(S172) allele represents a polymorphism rather than a spontaneous mutation
      because the two SF1 alleles can be traced to the hybrid mouse strain (C57L/J x
      A/HeJ) from which the original adrenal tumor was derived. The SF1(A172) allele
      also is found in C57Bl/6J and C57Bl/10J mice, whereas the SF1(S172) allele also
      is found in C3H/HeJ and DBA/2J mice. The two forms of SF1 had only modest
      differences in activity suggesting that the SF1 polymorphism per se is not
      directly responsible for ACTH resistance. Our results indicate that the SF1(S172)
      allele is a marker of ACTH resistance in this family of adrenocortical tumor
      cells.

PMID- 12239115
TI  - Anabolic actions of parathyroid hormone during bone growth are dependent on c
      fos.
AB  - PTH has anabolic and catabolic actions in bone that are not clearly understood.
      The protooncogene c-fos and other activating protein 1 family members are
      critical transcriptional mediators in bone, and c-fos is up-regulated by PTH. The
      purpose of this study was to examine the mechanisms of PTH and the role of c-fos
      in PTH-mediated anabolic actions in bone. Mice with ablation of c-fos (-/-) and
      their wild-type (+/+) and heterozygous (+/-) littermates were administered PTH
      for 17 d. The +/+ mice had increased femoral bone mineral density (BMD), whereas 
      /- mice had reduced BMD after PTH treatment. PTH increased the ash weight of +/+
      and +/-, but not -/-, femurs and decreased the calcium content of -/-, but not
      +/+ or +/-, femurs. Histomorphometric analysis showed that PTH increased
      trabecular bone volume in c-fos +/+, +/- vertebrae, but, in contrast, decreased
      trabecular bone in -/- vertebrae. Serum calcium levels in +/+ mice were greater
      than those in -/- mice, and PTH increased calcium in -/- mice. Histologically,
      PTH resulted in an exacerbation of the already widened growth plate and zone of
      hypertrophic chondrocytes but not the proliferating zone in -/- mice. PTH also
      increased calvarial thickness in +/+ mice, but not -/- mice. The c-fos -/- mice
      had lower bone sialoprotein and osteocalcin (OCN), but unaltered PTH-1 receptor
      mRNA expression in calvaria, suggesting an alteration in extracellular matrix.
      Acute PTH injection (8 h) resulted in a decrease in osteocalcin mRNA expression
      in wild-type, but unaltered expression in -/-, calvaria. These data indicate that
      c-fos plays a critical role in the anabolic actions of PTH during endochondral
      bone growth.

PMID- 12239116
TI  - Sex steroid metabolism in the tibial growth plate of the rat.
AB  - To assess whether growth plate-specific production of sex steroids is possible,
      we have surveyed the presence of several key-enzymes involved in androgen and
      estrogen metabolism in the tibial growth plate of female and male rats during
      development. Using in situ hybridization, mRNAs of aromatase p450, type I and II
      17beta-hydroxysteroid dehydrogenase (HSD), steroid sulfatase (STS), and 5alpha
      reductase were detected in proliferating and hypertrophic chondrocytes of the
      growth plate. The former three were strongly up-regulated around sexual
      maturation (7 wk), whereas the latter two were expressed at a relatively constant
      level during development. These data were supported by measuring aromatase, type
      I 17beta-HSD, and STS enzyme activities in chondrocytes collected from tibial
      growth plates at 1 and 7 wk of age. Of the enzymes studied, there were minor
      differences between the sexes in aromatase and 5alpha-reductase expression only.
      In conclusion, our findings clearly indicate the presence of various enzymes
      involved in sex steroid metabolism in the tibial growth plate, especially in
      sexually maturing rats, a timepoint at which sex steroids have major effects on
      longitudinal growth. Our data suggest that intracrinology in the rat growth plate
      can occur and may be a major source of local sex steroid delivery.

PMID- 12239118
TI  - Bone marrow adipocytes: a neglected target tissue for growth hormone.
AB  - Bone marrow (BM) contains numerous adipocytes. These share a common precursor
      with osteoblasts and chondrocytes, but their function is unknown. It is unclear
      what regulates the differentiation of these three different cell types, though
      their subsequent metabolic activity is under hormonal regulation. GH and estrogen
      stimulate bone growth and mineralization, by direct effects on chondrocytes and
      osteoblasts. GH also stimulates lipolysis in subcutaneous and visceral
      adipocytes. However, adipocytes in BM have largely been ignored as potential
      targets for GH or estrogen action. We have addressed this by measuring BM
      adipocyte number, perimeter and area as well as bone area and osteoblast activity
      in GH-deficient dwarf (dw/dw), normal, or ovariectomized (Ovx) rats, with or
      without GH, IGF-1, PTH, or estrogen treatment or high fat feeding. Marrow
      adipocyte numbers were increased 5-fold (P < 0.001) in dw/dw rats, and cell size
      was also increased by 20%. These values returned toward normal in dw/dw rats
      given GH but not when given IGF-1. Cancellous bone area and osteoblast number
      were significantly (P < 0.005) lower in dw/dw rats, though alkaline phosphatase
      (ALP) activity in individual osteoblasts was unchanged. GH treatment increased %
      osteoblast covered bone surface without affecting individual cell ALP activity.
      Ovariectomy in normal or dw/dw rats had no affect on marrow adipocyte number nor
      size, although estrogen treatment in ovariectomized (Ovx) normal rats did
      increase adipocyte number. Ovx decreased tibial cancellous bone area in normal
      rats (64%; P < 0.05) and decreased osteoblast ALP-activity (P < 0.01) but did not
      affect the percentage of osteoblast-covered bone surface. Estrogen replacement
      reversed these changes. While treatment with PTH by continuous sc infusion
      decreased cancellous bone (P < 0.05) and high fat feeding increased the size of
      BM adipocytes (P < 0.01), they did not affect BM adipocyte number. These results
      suggest that GH has a specific action on BM adipocytes that is not simply due to
      altered bone or fat metabolism. We conclude that the marrow adipocyte lineage is
      an important and specific target for GH action. The inverse relationship between
      adipocyte number and osteoblast covered bone surface, together with the well
      known effects of GH on epiphysial chondrocytes leads us to propose that GH plays
      two important roles on cells of all three lineages. During differentiation, it
      regulates the numbers of each cell type that are maintained from the common
      precursor lineage. Subsequently it has cell-specific effects on the metabolic
      activities of the differentiated cells. In the case of marrow adipocytes, GH
      dependent lipolysis could provide an important hormonally regulated local high
      energy source in bone.

PMID- 12239117
TI  - Calcitonin expression in rat anterior pituitary gland is regulated by ovarian
      steroid hormones.
AB  - Gonadotroph-derived calcitonin-like peptide (pit-CT) is a potent inhibitor of
      lactotroph function. We investigated the effect of ovarian hormones on pit-CT
      mRNA expression in the anterior pituitary (AP) gland of cycling female rats.
      Levels of mRNAs for pit-CT, CT receptor, prolactin (PRL), and beta-LH during 4-d
      estrous cycle were determined. In a second study, the effects of estrogens and
      progesterone on pit-CT and PRL mRNA levels were investigated. In a third group,
      the effect of estrogen or progesterone depletion on pit-CT mRNA expression was
      studied. In a fourth group, the effect of passive pit-CT immunization on PRL and
      LH mRNA expression was examined. Pit-CT mRNA levels varied during estrous cycle.
      They were highest in diestrus, but lowest in the evening of proestrus. CT
      receptor mRNA levels displayed smaller fluctuations. Estrogen repletion caused a
      decline in pit-CT mRNA expression in ovariectomized rats, but progesterone
      produced a marked increase. ICI 182,780 prevented the decline of pit-CT mRNA
      levels during late proestrus-estrus, but RU 486 attenuated pit-CT mRNA levels.
      Passive CT immunization in diestrus altered PRL and LH mRNA expression, and
      advanced the estrus cycle. These results suggest that pit-CT mRNA expression is
      regulated by ovarian hormones, and depletion of pit-CT advances their estrous
      cycle.

PMID- 12239119
TI  - Mammary gland development in transgenic male mice expressing human P450
      aromatase.
AB  - We recently generated a transgenic mouse strain that expresses the human
      aromatase gene under the ubiquitin C promoter (AROM+). We have previously shown
      that in these mice the serum estradiol concentration is highly elevated, whereas
      the testosterone concentration is decreased. In the present study we examined
      mammary gland development in AROM+ male mice at different ages and found that the
      mammary glands of AROM+ males undergo ductal and alveolar development
      morphologically resembling that of terminally differentiated female mammary
      glands, expressing mRNA for a milk protein gene (beta-casein). The male mammary
      glands also express multiple hormone receptors typical for female mammary gland:
      estrogen receptor alpha and beta, progesterone receptor, and PRL receptor.
      Furthermore, data showed activation of the Stat5 (signal transducer and activator
      of transcription 5) signaling pathway in the AROM+ male mammary gland.
      Interestingly, the phenotype observed is in part reversible. Treatment with
      finrozole, a specific aromatase inhibitor, caused an involution of the
      differentiated phenotype of the mammary gland, marked by the disappearance of
      alveolar structures and the majority of the tertiary side branches of the ducts.
      The present animal model is a valuable tool for better understanding the cellular
      and molecular mechanisms involved in the development of gynecomastia.

PMID- 12239120
TI  - Reproductive disturbances, pituitary lactotrope adenomas, and mammary gland
      tumors in transgenic female mice producing high levels of human chorionic
      gonadotropin.
AB  - To assess the consequences of prolonged exposure to elevated levels of LH/human
      chorionic gonadotropin (hCG) in the female, we developed a transgenic (TG) mouse
      model (hCGbeta+) that overexpresses the hCGbeta-subunit cDNA. Because of the
      promoter used, ubiquitin C, the transgene is expressed in multiple tissues,
      including the pituitary gland, in which coupling with the endogenous common alpha
      subunit results in synthesis of high levels of bioactive hCG. The TG females
      presented with precocious puberty, infertility, enhanced ovarian steroidogenesis,
      and abnormal uterine structure. Pituitary enlargement was evident from the age of
      2 months, which progressed to adenomas by the age of 10-12 months.
      Immunohistochemical studies and electron microscopy demonstrated lactotrope
      origin for the adenomas, associated with severe hyperprolactinemia. The mammary
      glands of TG females showed marked lobuloalveolar development followed by mammary
      tumors with characteristics of adenocarcinoma at the age of 9-12 months. More
      than 90% of penetrance and high frequency of metastasis (47%) was observed.
      Formation of the pituitary and mammary gland tumors was totally abolished by
      ovariectomy despite persistently elevated hCG levels. Taken together, these
      findings suggest that the hCG-induced aberrations of ovarian function are clearly
      responsible for the extragonadal tumors observed in these TG mice.

PMID- 12239121
TI  - Transgenic mice harboring murine luteinizing hormone receptor promoter/beta
      galactosidase fusion genes: different structural and hormonal requirements of
      expression in the testis, ovary, and adrenal gland.
AB  - In vivo regulation of the LH receptor (LHR) promoter was studied using transgenic
      (TG) mice harboring fusion genes containing three different lengths of the LHR
      promoter (7.4 kb, 2.1 kb, and 173 bp), fused with coding sequence of the
      Escherichia coli beta-galactosidase (beta-GAL) reporter gene. The length of the
      LHR promoter significantly affected the pattern of beta-GAL expression. In the
      testis the shortest promoter directed expression primarily of the full-length
      beta-GAL mRNA, but mainly truncated messages were transcribed from the longer LHR
      promoter/beta-GAL constructs. The case was reversed in the ovary and adrenal
      gland. Furthermore, we have recently detected strong LHR expression in the
      adrenal gland of female mice with chronically elevated serum LH. Therefore, the
      regulation of the adrenal LHR expression was addressed in the present study using
      the LHR/beta-GAL TG mice. Elevated LH levels were achieved in the LHR/beta-GAL
      mice either by gonadectomy or cross-breeding them with TG mice overexpressing a
      chimeric protein of bovine LH beta-subunit and the C-terminal fragment of human
      chorionic gonadotropin-beta. In both models, beta-GAL mRNA was found in the
      adrenal cortex when the 7.4-kb LHR promoter was applied but not in mice carrying
      the 173-bp LHR promoter. The 7.4-kb construct was activated also in the ovaries
      in the double TG LHR(beta-GAL)/bovine LH beta-subunit/C-terminal fragment of
      human chorionic gonadotropin-betamice in some theca-interstitial cells
      surrounding the follicles. Hence, the LHR promoter elements essential for
      directing beta-GAL expression to the adrenal gland and ovary (7.4 kb) are
      different from those recently shown to be essential for the testicular expression
      (173 bp). In conclusion, elevated serum LH concentrations were found seminal for
      the LHR promoter activation in the ovaries and adrenals, and different lengths of
      the promoter are responsible for reporter gene expression in the testis, ovary,
      and adrenal gland.

PMID- 12239122
TI  - Growth hormone is required for ovarian follicular growth.
AB  - To analyze the consequences of the absence of GH receptor (GHR) and GH-binding
      protein (GHBP) on female reproductive function, we used a mouse model in which
      the GHR/GHBP gene has been disrupted by homologous recombination. The major
      effect on reproductive function seen in GHR/GHBP knockout (KO) compared with wild
      type animals is a dramatic decrease in litter size; this defect is due to a
      reduction of the ovulation rate. The ovulatory response to exogenous gonadotropin
      treatment is also 3-fold reduced in GHR/GHBP KO compared with the wild-type
      ovaries. These results establish that the reduced rate of ovulation is
      essentially due to an ovarian defect rather than a deficiency in pituitary
      gonadotropins. The number of follicles per ovary is markedly reduced, although
      all categories of follicles are represented. Interestingly, the number of healthy
      follicles from antral and preovulatory stages is dramatically decreased in
      GHR/GHBP KO in comparison with wild-type follicles. The capacity of follicles to
      bind LH, FSH, and IGF-I was not diminished. IGF-I treatment using micropumps is
      not able to rescue either fertility or ovarian responsiveness to exogenous
      gonadotropins, suggesting that the effect of GH is independent of IGF-I. In
      conclusion, these results indicate that the reduction of litter size in GHR/GHBP
      KO mice is the consequence of an alteration of the growth of follicles and
      suggest that the effects of GH effects on follicular growth are independent of
      IGF-I.

PMID- 12239123
TI  - Growth hormone (GH) and GH-releasing peptide-6 increase brain insulin-like growth
      factor-I expression and activate intracellular signaling pathways involved in
      neuroprotection.
AB  - Beneficial effects of GH on memory, mental alertness, and motivation have been
      documented. Many actions of GH are mediated through IGF-I; hence, we investigated
      whether systemic administration of GH or GH-releasing peptide (GHRP)-6 modulates
      the brain IGF system. Treatment of adult male rats with GHRP-6 or GH for 1 wk
      significantly increased IGF-I mRNA levels in the hypothalamus, cerebellum, and
      hippocampus, with no effect in cerebral cortex. Expression of the IGF receptor
      and IGF-binding protein (IGFBP)-2 were not affected. Phosphorylation of Akt and
      Bad was stimulated in areas where IGF-I was increased, with no change in MAPK or
      glycogen synthase kinase-3beta. This suggests that GH and GHRP-6 activate
      phosphatidylinositol kinase intracellular pathways involved in cell survival in
      response to growth factors. Indeed, the antiapoptotic protein Bcl-2 was augmented
      in these same areas, with no change in the proapoptotic protein Bax. IGFBP-5,
      also reported to be involved in neuron survival processes, was increased mainly
      in the hypothalamus, suggesting a possible neuroendocrine role. In conclusion, GH
      and GHRP-6 modulate IGF-I expression in the central nervous system in an
      anatomically specific manner. This is coincident with activation of intracellular
      signaling pathways used by IGF-I and increased expression of proteins involved in
      cell survival or neuroprotection.

PMID- 12239124
TI  - SOM230: a new somatostatin peptidomimetic with potent inhibitory effects on the
      growth hormone/insulin-like growth factor-I axis in rats, primates, and dogs.
AB  - The goal of this project was to find a somatostatin (SRIF) analog with superior
      therapeutic potential. Receptor binding studies of new SRIF analogs were used to
      reveal SRIF substructures that interact with individual human SRIF receptor
      subtypes (sst1-sst5). Incorporation of these substructures into a stable
      cyclohexapeptide template led to SOM230, which binds with nanomolar affinity to
      sst1, sst2, sst3, and sst5. In rats, the inhibitory effect of SOM230 on GH was
      similar to SMS 201-995 (octreotide) at 1 h, but was 4-fold more potent at 6 h
      post injection, indicating increased metabolic stability. Treatment of rats with
      SOM230, at 1 and 10 micro g/kg.h, decreased IGF-I plasma levels, on d 2, by 68%
      and 90% (P < 0.01); whereas, under SMS 201-995 treatment, plasma IGF-I levels
      decreased by 28% and 49%, respectively. After a 2-wk infusion of rats, the
      suppression of IGF-I levels by SOM230 was still pronounced, whereas the response
      to SMS 201-995 was largely lost. This enhanced effect of SOM230 on IGF-I plasma
      levels was confirmed in an 8-wk study where both analogs were infused at 50 micro
      g/kg/h in rats. In rhesus monkey, SOM230 and SMS 201-995 treatment resulted in GH
      inhibition, with half-maximal inhibitory dose values of 0.5 and 0.4 micro g/kg,
      respectively, but plasma IGF-I levels were only lowered by SOM230 (-53%). In
      cynomolgus monkeys, a 2-wk infusion of SOM230, but to a much lesser extent of SMS
      201-995, lowered plasma GH levels significantly (from 16.3 to 1.8 ng/ml, P =
      0.007). Both in cynomolgus monkeys and beagle dogs, infusion of SOM230, but not
      SMS 201-995, lowered IGF-I levels significantly. In conclusion, SOM230 has a
      unique structure, binds almost universally to human ssts, and inhibits potently
      the GH/IGF-I axis cross-species. SOM230 is a candidate drug for clinical use.

PMID- 12239125
TI  - Estrogen accelerates gonadal recrudescence in photo-regressed male siberian
      hamsters.
AB  - Seasonal gonadal recrudescence in the male Siberian hamster is accompanied by the
      initiation of spermatogenesis, weight gain, and darkening of coat color. The
      downstream endocrine regulators responsible for these changes have been
      definitively identified. We have previously shown that the administration of
      exogenous 17beta-estradiol (E(2)) to adult male Siberian hamsters kept under long
      day photoperiod increased testicular mass without altering spermatogenesis. In
      this study, we examine if E(2) can initiate testicular growth in photo-regressed
      adult Siberian hamsters and if this testicular growth is accompanied by weight
      gain and pelage color change. Photo-regressed adult male Siberian hamsters were
      subcutaneously implanted with a 1 mm silastic capsule containing E(2) or
      cholesterol control. After 15 days, robust initiation of spermatogenesis was
      observed in E(2)-implanted animals in the absence of body weight and pelage color
      change. While circulating follicle-stimulating hormone (FSH) remained undetected
      in both control and E(2)-treated animals, E(2) significantly reduced pituitary
      gonadotropin stores. Overall, we showed E(2) stimulated gonadal recrudescence via
      a pathway that has diverged from body weight and pelage color change. Further, we
      demonstrated a novel role of E(2) in the initiation of spermatogenesis, possibly
      via a mechanism independent of FSH.

PMID- 12239126
TI  - Regulation of 1,25-dihydroxyvitamin d synthesis by intracellular vitamin d
      binding protein-1.
AB  - Control of 125-dihydroxyvitamin D (1,25-(OH)2D) synthesis is believed to be
      primarily at the level of expression of the vitamin D-1-hydroxylase (CYP1alpha;
      CYP1alpha) gene. Once transcribed, generation of product, as catalyzed by 1
      hydroxylase, depends upon the availability of various co-factors, molecular
      oxygen, electrons as well as substrate to the enzyme. Here we provide evidence
      that the quantity of product 1,25-(OH)2D generated also relies on the presence
      and level of expression of the intracellular vitamin D binding protein-1 (IDBP-1)
      and its capacity to promote 24-hydroxylase (CYP24) gene expression. Stable
      transfection of the IDBP-1 cDNA increased 1,25-(OH)2D synthesis up to 700% (p <
      0.001) in cells devoid of 24-hydroxylating potential but only 70% (p = 0.018) in
      cells in which the CYP24 gene is expressed. IDBP-1-mediated increase in 1,25
      (OH)2D production was independent of any change in CYP1alpha expression but
      highly dependent on the ability of exogenously-added or endogenously-synthesized
      1,25-(OH)2D to stimulate CYP24 gene expression. These data suggest that IDBP-1 is
      capable of controlling 1,25-(OH)2D production by modulating the delivery of 1)
      substrate 25-OHD to in the mitochondrial CYP1alpha gene product and 2) CYP1alpha
      product 1,25-(OH)2D to the vitamin D receptor for upregulation of expression of
      the catabolic CYP24 gene.

PMID- 12239127
TI  - Growth hormone-deficient dwarf animals are resistant to dimethylbenzanthracine
      (DMBA)-induced mammary carcinogenesis.
AB  - Increased plasma IGF-1 has consistently been associated with a variety of human
      cancers, whereas reduced levels of IGF-1 are associated with increased lifespan
      in other species. However, the aforementioned relationships are correlational or
      are derived from animal models that are not specific for growth hormone/IGF-1
      excess or deficiency. This study was designed to assess the effects of
      physiological changes in growth hormone and IGF-1 expression on
      dimethylbenzanthracine (DMBA)-induced mammary carcinogenesis. At 50 days of age,
      female heterozygous (dw/+) and growth hormone deficient dwarf (dw/dw) rats of the
      Lewis strain received a single dose of DMBA (80 micro g/g of body weight) via
      oral gavage. Animals were assigned to one of four experimental groups: a)
      heterozygous animals (normal size), b) dwarf animals administered vehicle, c)
      dwarf animals administered low levels of porcine growth hormone (50 micro g twice
      daily), and d) dwarf animals administered high levels of porcine growth hormone
      (200 micro g twice daily). At study termination, heterozygous animals exhibited a
      70% incidence of mammary tumors, whereas no tumors were observed in saline
      treated dwarf animals. Administration of either 100 micro g or 400 micro g growth
      hormone/day resulted in a dose dependent increase in incidence of mammary tumors
      (83 and 100%, respectively). Furthermore, heterozygous animals exhibited 1.5 +/-
      0.25 tumors per tumor-bearing animal, whereas dwarf animals administered 100
      micro g and 400 micro g growth hormone per day had 1.9 +/- 0.63 and 3.4 +/- 0.83
      tumors per animal, respectively. The present study demonstrates that DMBA-induced
      carcinogenesis is dependent on critical plasma levels of growth hormone and IGF
      1, and that growth hormone/IGF-1 deficient animals are resistant to DMBA-induced
      carcinogenesis.

PMID- 12239128
TI  - Goldfish ghrelin: molecular characterization of the complementary
      deoxyribonucleic acid, partial gene structure and evidence for its stimulatory
      role in food intake.
AB  - Complementary deoxyribonucleic acid (cDNA) encoding goldfish preproghrelin was
      identified using rapid amplification of the cDNA ends (RACE) and reverse
      transcription (RT)-polymerase chain reaction (PCR). The 490 bp cDNA encodes a 103
      amino acid preproghrelin which has a 26 amino acid signal region, 19 amino acid
      mature peptide and a 55 amino acid C-terminal peptide region. The mature peptide
      region of goldfish ghrelin has two putative cleavage sites and amidation signals
      (GRR); one after 12 amino acids and the other after 19 amino acids. The serine
      (S) in the second amino acid position in the "active core" of ghrelin is
      substituted with threonine (T). The goldfish ghrelin gene has four exons and
      three short introns and resembles the human ghrelin gene. Ghrelin messenger RNA
      (mRNA) expression was detected in the brain, pituitary, intestine, liver, spleen
      and gill by RT-PCR followed by Southern blot analysis, and in the intestine by
      Northern blot. Intracerebroventricular (ICV) injection of n-octanoylated goldfish
      ghrelin (1-19) stimulates food intake in goldfish.

PMID- 12239129
TI  - Effects of prolactin deficiency on myelopoiesis and splenic T lymphocyte
      proliferation in thermally injured mice.
AB  - The importance of prolactin (PRL) in mammopoiesis and milk production is
      undisputed. However, previous studies investigating the role of PRL in immune
      function have yielded inconsistencies. These inconsistencies have led to our
      hypothesis that the immunomodulatory effects of PRL are only manifest under
      conditions in which the organism is subjected to stress. Thermal injury is a well
      known stressor. The goal of this study was to determine whether the lack of PRL
      enhanced the negative effects of thermal injury-induced immune alterations
      utilizing a mouse model in which the PRL gene had been disrupted. Mice received
      either sham or burn treatment, and were sacrificed 4 days later. The immune
      parameters studied were the capacity of bone marrow cells to form granulocyte
      macrophage colony forming units (GM-CFU) in the presence of granulocyte
      macrophage colony stimulating factor, and the ability of the splenic T
      lymphocytes to proliferate in response to phytohemagglutin (PHA). As shown by
      others, our results reveal that burn increased the number of GM-CFU compared to
      sham controls; however, this elevation was only significant in the PRL-/- mice.
      Thermal injury increased PHA-stimulated proliferation of splenic T lymphocytes,
      however this increase was only significant in the PRL+/- group. We conclude that
      under conditions of a controlled stress event (thermal injury) [a] the increase
      in the GM-CFU is exaggerated in the absence of PRL, and [b] the enhancement of
      PHA-induced proliferation of splenic lymphocytes required PRL. This study
      supports the hypothesis that the immunomodulatory effects of PRL are manifest
      when the organism is subjected to stress.

PMID- 12239135
TI  - Erythroid-specific expression of the erythropoietin receptor rescued its null
      mutant mice from lethality.
AB  - Erythropoietin (Epo) and its receptor (EpoR) are indispensable to erythropoiesis.
      Although roles besides angiogenesis, such as neuroprotection and heart
      development, have been reported for the Epo-EpoR system, the precise contribution
      of Epo-EpoR to these nonhematopoietic tissues requires clarification. Exploiting
      a GATA-1 minigene cassette with hematopoietic regulatory domains, we established
      2 lines of transgene-rescued EpoR-null mutant mice expressing EpoR exclusively in
      the hematopoietic lineage. Surprisingly, despite the lack of EpoR expression in
      nonhematopoietic tissues, these mice develop normally and are fertile. As such,
      we could exploit them for analyzing the roles of the Epo-EpoR system in adult
      hematopoiesis and in nonhematopoietic tissues. These rescued lines showed a
      differential level of EpoR expression in erythroid cells; one expressed
      approximately 40%, and the other expressed 120% of the wild-type EpoR level. A
      colony formation assay showed that erythroid progenitors in the 2 mutant lines
      exhibit distinct sensitivity to Epo. The circulating Epo level was much higher in
      the transgenic line with a lower EpoR expression. In response to induced anemia,
      the plasma Epo concentrations increased in both lines. Notably, the timing of the
      peak of plasma Epo concentration was delayed in both lines of rescued mice
      compared with wild type, suggesting that, in wild-type mice, nonhematopoietic
      EpoR contributes to the regulation of plasma Epo concentration. We thus conclude
      that nonhematopoietic expression of EpoR is dispensable to normal mouse
      development and that the expression level of EpoR regulates erythropoiesis by
      controlling the sensitivity of erythroid progenitors to Epo.

PMID- 12239136
TI  - Inherited predisposition to CLL is detectable as subclinical monoclonal B
      lymphocyte expansion.
AB  - Monoclonal chronic lymphocytic leukemia (CLL)-phenotype cells are detectable in
      3.5% of otherwise healthy persons using flow cytometric analysis of
      CD5/CD20/CD79b expression on CD19-gated B cells. To determine whether detection
      of such CLL-phenotype cells is indicative of an inherited predisposition, we
      examined 59 healthy, first-degree relatives of patients from 21 families with
      CLL. CLL-phenotype cells were detected in 8 of 59 (13.5%) relatives, representing
      a highly significant increase in risk (P =.00002). CLL-phenotype cell levels were
      stable with time and had the characteristics of indolent CLL. Indolent and
      aggressive clinical forms were found in family members, suggesting that
      initiation and proliferation involves distinct factors. The detection of CLL
      phenotype cells provides a surrogate marker of carrier status, potentially
      facilitating gene identification through mapping in families and direct analysis
      of isolated CLL-phenotype cells.

PMID- 12239137
TI  - The World Health Organization (WHO) classification of the myeloid neoplasms.
AB  - A World Health Organization (WHO) classification of hematopoietic and lymphoid
      neoplasms has recently been published. This classification was developed through
      the collaborative efforts of the Society for Hematopathology, the European
      Association of Hematopathologists, and more than 100 clinical hematologists and
      scientists who are internationally recognized for their expertise in
      hematopoietic neoplasms. For the lymphoid neoplasms, this classification provides
      a refinement of the entities described in the Revised European-American Lymphoma
      (REAL) Classification-a system that is now used worldwide. To date, however,
      there has been no published explanation or rationale given for the WHO
      classification of the myeloid neoplasms. The purpose of this communication is to
      outline briefly the WHO classification of malignant myeloid diseases, to draw
      attention to major differences between it and antecedent classification schemes,
      and to provide the rationale for those differences.

PMID- 12239138
TI  - Use of epoetin in patients with cancer: evidence-based clinical practice
      guidelines of the American Society of Clinical Oncology and the American Society
      of Hematology.
AB  - Anemia resulting from cancer or its treatment is an important clinical problem
      increasingly treated with the recombinant hematopoietic growth factor
      erythropoietin. To address uncertainties regarding indications and efficacy, the
      American Society of Clinical Oncology and the American Society of Hematology
      developed an evidence-based clinical practice guideline for the use of epoetin in
      patients with cancer. The guideline panel found good evidence to recommend use of
      epoetin as a treatment option for patients with chemotherapy-associated anemia
      with a hemoglobin (Hgb) concentration below 10 g/dL. Use of epoetin for patients
      with less severe anemia (Hgb level below 12 g/dL but never below 10 g/dL) should
      be determined by clinical circumstances. Good evidence from clinical trials
      supports the use of subcutaneous epoetin thrice weekly (150 U/kg) for a minimum
      of 4 weeks. Less strong evidence supports an alternative weekly (40 000 U/wk)
      dosing regimen, based on common clinical practice. With either administration
      schedule, dose escalation should be considered for those not responding to the
      initial dose. In the absence of response, continuing epoetin beyond 6-8 weeks
      does not appear to be beneficial. Epoetin should be titrated once the hemoglobin
      concentration reaches 12 g/dL. Evidence from one randomized controlled trial
      supports use of epoetin for patients with anemia associated with low-risk
      myelodysplasia not receiving chemotherapy; however, there are no published high
      quality studies to support its use for anemia in other hematologic malignancies
      in the absence of chemotherapy. Therefore, for anemic patients with hematologic
      malignancies it is recommended that physicians initiate conventional therapy and
      observe hematologic response before considering use of epoetin.

PMID- 12239139
TI  - CCR5-binding chemokines modulate CXCL12 (SDF-1)-induced responses of progenitor B
      cells in human bone marrow through heterologous desensitization of the CXCR4
      chemokine receptor.
AB  - Although the SDF-1 (CXCL12)/CXCR4 axis is important for B-cell development, it is
      not yet clear to what extent CC chemokines might influence B lymphopoiesis. In
      the current study, we characterized CC chemokine receptor 5 (CCR5) expression and
      function of primary progenitor B-cell populations in human bone marrow. CCR5 was
      expressed on all bone marrow B cells at levels between 150 and 200 molecules per
      cell. Stimulation of bone marrow B cells with the CCR5-binding chemokine
      macrophage inflammatory protein 1beta (MIP-1beta; CCL4) did not cause chemotaxis,
      but CCL4 was able to trigger potent calcium mobilization responses and activation
      of the mitogen-activated protein kinase (MAPK) pathway in developing B cells. We
      also determined that CCR5-binding chemokines MIP-1alpha (CCL3), CCL4, and RANTES
      (CCL5), specifically by signaling through CCR5, could affect all progenitor B
      cell populations through a novel mechanism involving heterologous desensitization
      of CXCR4. This cross-desensitization of CXCR4 was manifested by the inhibition of
      CXCL12-induced calcium mobilization, MAPK activation, and chemotaxis. These
      findings indicate that CCR5 can indeed mediate biologic responses of bone marrow
      B cells, even though these cell populations express low levels of CCR5 on their
      cell surface. Thus, by modulation of CXCR4 function, signaling through CCR5 may
      influence B lymphopoiesis by affecting the migration and maturation of B-cell
      progenitors in the bone marrow microenvironment.

PMID- 12239140
TI  - Transgenic overexpression of human IL-17E results in eosinophilia, B-lymphocyte
      hyperplasia, and altered antibody production.
AB  - We have identified and cloned a novel human cytokine with homology to cytokines
      of the interleukin-17 (IL-17) family, which we have termed human IL-17E (hIL
      17E). With the identification of several IL-17 family members, it is critical to
      understand the in vivo function of these molecules. We have generated transgenic
      mice overexpressing hIL-17E using an apolipoprotein E (ApoE) hepatic promoter.
      These mice displayed changes in the peripheral blood, particularly, a 3-fold
      increase in total leukocytes consisting of increases in eosinophils, lymphocytes,
      and neutrophils. Splenomegaly and lymphoadenopathy were predominant and included
      marked eosinophil infiltrates and lymphoid hyperplasia. CCR3(+) eosinophils
      increased in the blood and lymph nodes of the transgenic mice by 50- and 300
      fold, respectively. Eosinophils also increased 8- to 18-fold in the bone marrow
      and spleen, respectively. In the bone marrow, most of the eosinophils had an
      immature appearance. CD19(+) B cells increased 2- to 5-fold in the peripheral
      blood, 2-fold in the spleen, and 10-fold in the lymph nodes of transgenic mice,
      whereas CD4(+) T lymphocytes increased 2-fold in both blood and spleen. High
      serum levels of the cytokines IL-2, IL-4, IL-5, granulocyte colony-stimulating
      factor, eotaxin, and interferon gamma were observed. Consistent with B-lymphocyte
      increases, serum immunoglobulin (Ig) M, IgG, and IgE were significantly elevated.
      Antigenic challenge of the transgenic mice with keyhole limpet hemocyanin (KLH)
      resulted in a decrease in anti-KLH IgG accompanied by increases of anti-KLH IgA
      and IgE. In situ hybridization of transgenic tissues revealed that IL-17Rh1 (IL
      17BR/Evi27), a receptor that binds IL-17E, is up-regulated. Taken together, these
      data indicate that IL-17E regulates hematopoietic and immune functions,
      stimulating the development of eosinophils and B lymphocytes. The fact that hIL
      17E overexpression results in high levels of circulating eosinophils, IL-4, IL-5,
      eotaxin, and IgE suggests that IL-17E may be a proinflammatory cytokine favoring
      Th2-type immune responses.

PMID- 12239141
TI  - Successful treatment of posttransplantation lymphoproliferative disorder (PTLD)
      following renal allografting is associated with sustained CD8(+) T-cell
      restoration.
AB  - Posttransplantation lymphoproliferative disorder (PTLD) is a life-threatening
      Epstein-Barr virus (EBV)-associated B-cell malignancy occurring in 1% to 2% of
      renal transplantation patients. Host- and PTLD-related factors determining the
      likelihood of tumor response following reduction of immune suppression (IS) and
      antiviral therapy remain largely unknown. Standard therapy for PTLD is not well
      established. Eleven consecutive renal transplantation patients who developed EBV
      positive PTLD 8 to 94 months after allografting were uniformly treated with
      acyclovir and IS reduction. All PTLDs were EBV-positive diffuse large B-cell
      lymphomas. Ten patients (91%) obtained a durable complete response (CR), and 9
      (82%) have remained in continuous CR with a median follow-up of 29 months. Five
      patients (45%) lost their allograft. Of these, 4 patients had PTLD affecting the
      transplanted kidney. Peripheral blood CD8(+) T cells increased significantly (P
      =.0078) from baseline in 8 responders available for analysis. One of 2 patients
      whose absolute CD8(+) T-cell count subsequently dropped to baseline after IS
      reduction relapsed. The expanded CD8(+) T cells from 2 responders specifically
      recognized an immunodominant peptide from the EBV lytic gene BZLF-1. Another
      lytic EBV gene, thymidine kinase, was expressed in all 8 PTLDs tested. IS
      reduction and antiviral therapy for PTLD after renal transplantation is a highly
      successful therapeutic combination, but the risk of graft rejection is
      significant, particularly in patients with PTLD involving the renal allograft. A
      sustained expansion of CD8(+) T cells and a cellular immune response to EBV lytic
      antigens may be important for PTLD clearance in renal transplantation patients.

PMID- 12239142
TI  - Immunophenotypic clustering of myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDSs) are heterogeneous diseases of bone marrow (BM)
      cell precursors for which immunophenotypic characterization is still considered
      irrelevant despite the accuracy and sensitivity of flow cytometry techniques. The
      aim of this study was to determine whether immunophenotypic abnormalities could
      be defined in MDSs and could correlate with the French-American-British
      classification and cytogenetics. Analysis was performed on 275 BM samples (207
      MDS patients, 68 controls) and 25 control blood samples. Immunophenotyping was
      based on a primary gating of blast cells, monocytes, and granulocytes according
      to CD45 antigen expression and side scatter light diffraction. Immunophenotypic
      hierarchical clustering was performed to analyze the results. The data obtained
      show that (1) immunophenotypic clustering partly discriminates patients with
      refractory anemia with excess blasts/refractory anemia with excess blasts in
      transformation (RAEB/RAEB-T), chronic myelomonocytic leukemia (CMML), and
      refractory anemia/refractory anemia with ring sideroblasts (RA/RARS) for CD45(lo)
      blast cells and patients with RA/CMML, RARS, and RAEB/RAEB-T for CD45(hi)/side
      scatter(hi) (SS(hi)) granulocytes; (2) the most discriminating markers were CD16,
      CD34, CD36, CD38, CD71, and HLA-DR for blast cells and CD11b, CD13, CD33, CD36,
      CD38, CD71, and HLA-DR for CD45(hi)/SS(hi) granulocytes; (3) clusters related to
      CD34 expression were associated with high levels of blast cells on BM smear; (4)
      clusters related to high levels of CD36 expression on CD45(lo) blast cells and
      CD45(hi)/SS(hi) granulocytes were associated with a poor International Prognosis
      Scoring System score; and (5) high levels of CD71 expression on CD45(hi)/SS(hi)
      granulocytes were associated with the RARS category. These results show a close
      relationship between immunophenotypic abnormalities and BM dysplasia and suggest
      that flow cytometry could be a future tool for the characterization of MDSs.

PMID- 12239143
TI  - Outcome of treatment in adults with Philadelphia chromosome-positive acute
      lymphoblastic leukemia--results of the prospective multicenter LALA-94 trial.
AB  - From 1994 to 2000, 154 adults with Philadelphia chromosome-positive (Ph(+))
      and/or BCR-ABL(+) acute lymphoblastic leukemia (ALL) were treated according to a
      prospective trial (median follow-up, 4.5 years) with the aim to study the
      prognostic value of early response to therapy and the role of stem cell
      transplantation (SCT) in first complete remission (CR). All patients received a
      standard induction course followed by a course of mitoxantrone and intermediate
      dose cytarabine (HAM). After each course, minimal residual disease was tested by
      specific reverse transcriptase-polymerase chain reaction (RT-PCR) (median
      sensitivity, 10(-5)). Allogeneic SCT (if a donor) or autologous SCT (if not) was
      planned at 3 months in all patients in CR after HAM. CR rates after induction,
      after HAM, and at 3 months were 53%, 67%, and 62%, respectively. High leukocyte
      count and m-bcr subtype were the 2 identified bad-prognosis factors for CR at 3
      months, both superseded by a poor early response assessed at day 8 of the
      induction course. HAM-associated salvage rate was higher in patients with M-bcr
      than in those with m-bcr ALL (55% vs 30%; P =.05). In the 103 patients eligible
      for SCT, the existence of a donor and the negative BCR-ABL status after HAM were
      independently predictive of remission duration (P <.001 and.01, respectively) and
      survival (P =.02 and.01, respectively). Relapse was the most common cause of
      treatment failure in all patient groups. Allogeneic SCT in first CR is the
      current best treatment option in adults with the disease. New strategies must be
      tested during early phases of therapy to increase the rate of BCR-ABL(-)
      remissions.

PMID- 12239144
TI  - Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy
      and bone marrow transplantation.
AB  - Hemophagocytic lymphohistiocytosis (HLH) comprises familial (primary)
      hemophagocytic lymphohistiocytosis (FHL) and secondary HLH (SHLH), both
      clinically characterized by fever, hepatosplenomegaly, and cytopenia. FHL, an
      autosomal recessive disease invariably fatal when untreated, is associated with
      defective triggering of apoptosis and reduced cytotoxic activity, resulting in a
      widespread accumulation of T lymphocytes and activated macrophages. In 1994 the
      Histiocyte Society initiated a prospective international collaborative
      therapeutic study (HLH-94), aiming at improved survival. It combined chemotherapy
      and immunotherapy (etoposide, corticosteroids, cyclosporin A, and, in selected
      patients, intrathecal methotrexate), followed by bone marrow transplantation
      (BMT) in persistent, recurring, and/or familial disease. Between July 1, 1994,
      and June 30, 1998, 113 eligible patients aged no more than 15 years from 21
      countries started HLH-94. All had either an affected sibling (n = 25) and/or
      fulfilled the Histiocyte Society diagnostic criteria. At a median follow-up of
      3.1 years, the estimated 3-year probability of survival overall was 55% (95%
      confidence interval +/- 9%), and in the familial cases, 51% (+/- 20%). Twenty
      enrolled children were alive and off therapy for more than 12 months without BMT.
      For patients who received transplants (n = 65), died prior to BMT (n = 25), or
      were still on therapy (n = 3), the 3-year survival was 45% (+/- 10%). The 3-year
      probability of survival after BMT was 62% (+/- 12%). HLH-94 is very effective,
      allowing BMT in most patients. Survival of children with HLH has been greatly
      improved.

PMID- 12239145
TI  - Current trends in hematopoietic stem cell transplantation in Europe.
AB  - Major changes have occurred in the transplantation of hematopoietic stem cells
      (HSCs) during the last decade. This report reveals the changes, reflects current
      status, and provides medium-term projections of HSC transplantation (HSCT)
      development in Europe. Data on 132 963 patients, 44 165 with allogeneic HSC
      transplant (33%) and 88 798 with an autologous HSC transplant (67%), collected
      prospectively from 619 centers by the European Group for Blood and Marrow
      Transplantation (EBMT) in 35 European countries between 1990 (4234 HSCTs) and
      2000 (19 136 HSCTs) illustrate utilization of HSCT. HSCT increased in all
      European countries and for all indications. There were major differences
      depending on disease indication and donor type. Transplantation rates (numbers of
      HSCTs per 10 million inhabitants) varied from less than 1 for some rare
      indications to 37.7 +/- 4.1 for acute myeloid leukemia in allogeneic HSCT or 95.5
      +/- 13.5 for non-Hodgkin lymphoma in autologous HSCT. There were indications with
      a steady, continuing increase and others with initial increase but subsequent
      decrease. Projections on medium-term development for each disease based on a
      weighted sensitivity analysis predict an ongoing increase in allogeneic HSCT
      except for chronic myeloid leukemia. In autologous HSCT they predict an increase
      for lymphoproliferative disorders, acute myeloid leukemia, myelodysplastic
      syndromes, and some solid tumors but a decrease for most solid tumors, acute
      lymphoid leukemia, and chronic myeloid leukemia. Transplantation rates can be
      predicted with reasonable sensitivity for most disease indications. Despite
      marked changes in the rapidly developing field of HSCT, this information on
      current use, trends, and midterm predictions forms a rational basis for patient
      counseling and health care planning.

PMID- 12239146
TI  - Internal tandem duplication of FLT3 in relapsed acute myeloid leukemia: a
      comparative analysis of bone marrow samples from 108 adult patients at diagnosis
      and relapse.
AB  - Analysis of internal tandem duplications of FLT3 (FLT3/ITD) was performed on bone
      marrow samples obtained at diagnosis and relapse from 108 adult patients with de
      novo acute myeloid leukemia (AML) to determine the role of this mutation in
      leukemic relapse. Eighty-three patients had wild-type FLT3 at both diagnosis and
      relapse, 16 had FLT3/ITD at both stages, whereas 8 had acquired the mutation and
      1 had lost it at relapse. Using Genescan analysis, we found that FLT3/ITD levels
      at first relapse were significantly higher than those at diagnosis (mean +/- SE,
      40.5% +/- 4.8% versus 17.9% +/- 3.6%, P <.001). The increase in mutation levels
      at relapse as compared with diagnosis did not correlate with the difference in
      blast cell percentages at both stages (P =.777). A hemizygous deletion of wild
      type FLT3 was found in 4 patients at relapse compared to none at diagnosis. Nine
      of the 11 patients carrying a single mutation at diagnosis relapsed with an
      identical mutation. All 6 patients with more than one FLT3/ITD mutation at
      diagnosis showed changes in mutation patterns and levels at first relapse;
      however, each patient retained at least one mutation in the relapse sample. The
      changes of mutation patterns had implications for the monitoring of minimal
      residual disease. Our results suggest that FLT3/ITD may contribute as the initial
      transforming event in AML, and relapse can reflect the selection and outgrowth of
      a mutant clone or evolution of a new clone harboring this mutation.

PMID- 12239147
TI  - Studies of FLT3 mutations in paired presentation and relapse samples from
      patients with acute myeloid leukemia: implications for the role of FLT3 mutations
      in leukemogenesis, minimal residual disease detection, and possible therapy with
      FLT3 inhibitors.
AB  - FLT3 mutations, either internal tandem duplications (ITDs) or aspartate residue
      835 (D835) point mutations, are present in approximately one third of patients
      with acute myeloid leukemia (AML) and have been associated with an increased
      relapse rate. We have studied FLT3 mutations in paired presentation and relapse
      samples to ascertain the biology of these mutations and to evaluate whether they
      can be used as markers of minimal residual disease. At diagnosis, 24 patients
      were wild-type FLT3, and 4 acquired a FLT3 mutation at relapse (2 D835(+), 2
      ITD(+)), with a further patient acquiring an ITD at second relapse. Of 20
      patients positive at diagnosis (18 ITD(+), 2 D835(+)), 5 who were all originally
      ITD(+) had no detectable mutation at relapse, as determined by a sensitive
      radioactive polymerase chain reaction. One of these patients had acquired an N
      Ras mutation not detectable at presentation. Furthermore, another patient had a
      completely different ITD at relapse, which could not be detected in the
      presentation sample. These results indicate that FLT3 mutations are secondary
      events in leukemogenesis, are unstable, and thus should be used cautiously for
      the detection of minimal residual disease.

PMID- 12239148
TI  - Use of peripheral blood instead of bone marrow to monitor residual disease in
      children with acute lymphoblastic leukemia.
AB  - In children with acute lymphoblastic leukemia (ALL), response to treatment is
      assessed by bone marrow aspiration. We investigated whether minimal residual
      disease (MRD) can be effectively monitored in peripheral blood. We used flow
      cytometric techniques capable of detecting 1 leukemic cell among 10 000 or more
      normal cells to compare MRD measurements in 718 pairs of bone marrow and
      peripheral blood samples collected from 226 children during treatment for newly
      diagnosed ALL. MRD was detected in marrow and blood in 72 pairs and in marrow but
      not in blood in 67 pairs; it was undetectable in the remaining 579 pairs.
      Remarkably, findings in marrow and blood were completely concordant in the 150
      paired samples from patients with T-lineage ALL: for each of the 35 positive
      marrow samples, the corresponding blood sample was positive. In B-lineage ALL,
      however, only 37 of 104 positive marrow samples had a corresponding positive
      blood sample. Notably, peripheral blood MRD in these patients was associated with
      a very high risk for disease recurrence. The 4-year cumulative incidence of
      relapse in patients with B-lineage ALL was 80.0% +/- 24.9% for those who had
      peripheral blood MRD at the end of remission induction therapy but only 13.3% +/-
      9.1% for those with MRD confined to the marrow (P =.007). These results indicate
      that peripheral blood may be used to monitor MRD in patients with T-lineage ALL
      and that peripheral blood MRD may provide strong prognostic information in
      patients with B-lineage ALL.

PMID- 12239149
TI  - The incidence of venous thromboembolism in thrombophilic children: a prospective
      cohort study.
AB  - Antithrombin and protein C and S defects, factor V Leiden mutation, and G20210A
      prothrombin gene mutation are well-recognized risk factors for venous
      thromboembolism (VTE) in adults, especially during circumstantial situations such
      as trauma, immobilization, surgery, or oral contraceptive treatment. The
      relevance of these defects in predisposing children to VTE is still undefined. In
      a prospective cohort study we assessed the incidence of spontaneous and risk
      period-related VTE in asymptomatic children (aged 1-14 years), who were family
      members of a proband with an objectively diagnosed venous thromboembolic event
      and a documented single thrombophilic abnormality. We enrolled 143 children from
      63 families. Of them, 81 (56.6%) were carriers of an inherited defect, whereas
      the remaining 62 were free from known genetic or acquired causes of
      thrombophilia. The mean observation period was 5 years (range, 1-8 years) in each
      group. Thirty-one risk periods occurred in the carriers group and 20 in
      noncarriers. Neither spontaneous nor risk period-related VTE occurred in either
      group during 395 and 296 observation years, respectively. However, circumstances
      where most of the pediatric thromboses occur (insertion of central venous lines,
      cancer, and cardiovascular surgery) were not encountered. In conclusion, the
      thrombotic risk in otherwise healthy children with a single identified
      thrombophilic defect appears to be very low. Common triggering conditions for VTE
      in thrombophilic adults do not seem to increase the thrombotic risk in children
      carrying the same inherited defect. Accordingly, screening for thrombophilia in
      otherwise healthy children younger than 15 years who belong to families with
      inherited defects predisposing to thrombosis seems unjustified.

PMID- 12239150
TI  - Long-term reversal of chronic anemia using a hypoxia-regulated erythropoietin
      gene therapy.
AB  - Anemia is a common clinical problem, and there is much interest in its role in
      promoting left ventricular hypertrophy through increasing cardiac workload.
      Normally, red blood cell production is adjusted through the regulation of
      erythropoietin (Epo) production by the kidney. One important cause of anemia is
      relative deficiency of Epo, which occurs in most types of renal disease.
      Clinically, this can be corrected by supplementation with recombinant Epo. Here
      we describe an oxygen-regulated gene therapy approach to treating homozygous
      erythropoietin-SV40 T antigen (Epo-TAg(h)) mice with relative erythropoietin
      deficiency. We used vectors in which murine Epo expression was directed by an
      Oxford Biomedica hypoxia response element (OBHRE) or a constitutive
      cytomegalovirus (CMV) promoter. Both corrected anemia, but CMV-Epo-treated mice
      acquired fatal polycythemia. In contrast, OBHRE-Epo corrected the hematocrit
      level in anemic mice to a normal physiologic level that stabilized without
      resulting in polycythemia. Importantly, the OBHRE-Epo vector had no significant
      effect on the hematocrit of control mice. Homozygous Epo-TAg(h) mice display
      cardiac hypertrophy, a common adaptive response in patients with chronic anemia.
      In the OBHRE-Epo-treated Epo-TAg(h) mice, we observed a significant reversal of
      cardiac hypertrophy. We conclude that the OBHRE promoter gives rise to
      physiologically regulated Epo secretion such that the hematocrit level is
      corrected to healthy in anemic Epo-TAg(h) mice. This establishes that a hypoxia
      regulatory mechanism similar to the natural mechanism can be achieved, and it
      makes EPO gene therapy more attractive and safer in clinical settings. We
      envisage that this control system will allow regulated delivery of therapeutic
      gene products in other ischemic settings.

PMID- 12239151
TI  - S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1
      and RAD51.
AB  - Fanconi anemia (FA) is a human autosomal recessive cancer susceptibility disorder
      characterized by cellular sensitivity to mitomycin C and defective cell-cycle
      progression. Six FA genes (corresponding to subtypes A, C, D2, E, F, and G) have
      been cloned, and the encoded FA proteins interact in a common pathway. DNA damage
      activates this pathway, leading to monoubiquitination of the downstream FANCD2
      protein and targeting to nuclear foci containing BRCA1. In the current study, we
      demonstrate that FANCD2 also undergoes monoubiquitination during S phase of the
      cell cycle. Monoubiquitinated FANCD2 colocalizes with BRCA1 and RAD51 in S-phase
      specific nuclear foci. Monoubiquitination of FANCD2 is required for normal cell
      cycle progression following cellular exposure to mitomycin C. Our data indicate
      that the monoubiquitination of FANCD2 is highly regulated, and they suggest that
      FANCD2/BRCA1 complexes and FANCD2/RAD51 complexes participate in an S-phase
      specific cellular process, such as DNA repair by homologous recombination.

PMID- 12239152
TI  - Tumor necrosis factor-related apoptosis-inducing ligand induces monocytic
      maturation of leukemic and normal myeloid precursors through a caspase-dependent
      pathway.
AB  - Treatment of the human HL-60 cell line with tumor necrosis factor (TNF)-related
      apoptosis-inducing ligand (TRAIL) resulted in rapid (6-24 hours) cytotoxicity
      associated with progressive maturation of the surviving cells along the monocytic
      lineage. The occurrence of monocytic maturation was demonstrated by a significant
      increase of both CD14 and CD11b surface expression, the acquisition of
      morphologic features typical of mature monocytes, and phagocytic capacity in
      TRAIL-treated cultures. By using selective pharmacologic inhibitors, it was
      possible to demonstrate that activation of the caspase cascade played a crucial
      role in mediating TRAIL cytotoxicity and monocytic maturation of HL-60 cells.
      Moreover, experiments performed using agonistic polyclonal antibodies, which
      mimic the interactions between TRAIL and each TRAIL receptor, indicated that
      TRAIL-R1 was responsible for mediating the TRAIL-induced maturation. Importantly,
      the maturational effects of TRAIL were observed also in primary normal CD34(+)
      cells, seeded in serum-free liquid cultures for 4 to 8 days in the presence of
      SCF + GM-CSF. After treatment with TRAIL for 3 additional days, a significant
      increase in CD14 and CD11b expression, coupled with an increased number of mature
      monocytes and macrophages, was noticed in the absence of cytotoxicity. These data
      disclose a novel role for TRAIL as a positive regulator of myeloid
      differentiation. Moreover, the dichotomous effect of TRAIL on malignant cells
      (early induction of apoptosis and monocytic maturation of the surviving cells)
      might have important therapeutic implications for the treatment of acute myeloid
      leukemia.

PMID- 12239153
TI  - The SCL complex regulates c-kit expression in hematopoietic cells through
      functional interaction with Sp1.
AB  - The combinatorial interaction among transcription factors is believed to
      determine hematopoietic cell fate. Stem cell leukemia (SCL, also known as TAL1 [T
      cell acute lymphoblastic leukemia 1]) is a tissue-specific basic helix-loop-helix
      (bHLH) factor that plays a central function in hematopoietic development;
      however, its target genes and molecular mode of action remain to be elucidated.
      Here we show that SCL and the c-Kit receptor are coexpressed in hematopoietic
      progenitors at the single-cell level and that SCL induces c-kit in chromatin, as
      ectopic SCL expression in transgenic mice sustains c-kit transcription in
      developing B lymphocytes, in which both genes are normally down-regulated.
      Through transient transfection assays and coimmunoprecipitation of endogenous
      proteins, we define the role of SCL as a nucleation factor for a multifactorial
      complex (SCL complex) that specifically enhances c-kit promoter activity without
      affecting the activity of myelomonocytic promoters. This complex, containing
      hematopoietic-specific (SCL, Lim-only 2 (LMO2), GATA-1/GATA-2) and ubiquitous
      (E2A, LIM- domain binding protein 1 [Ldb-1]) factors, is tethered to DNA via a
      specificity protein 1 (Sp1) motif, through direct interactions between elements
      of the SCL complex and the Sp1 zinc finger protein. Furthermore, we demonstrate
      by chromatin immunoprecipitation that SCL, E2A, and Sp1 specifically co-occupy
      the c-kit promoter in vivo. We therefore conclude that c-kit is a direct target
      of the SCL complex. Proper activation of the c-kit promoter depends on the
      combinatorial interaction of all members of the complex. Since SCL is down
      regulated in maturing cells while its partners remain expressed, our observations
      suggest that loss of SCL inactivates the SCL complex, which may be an important
      event in the differentiation of pluripotent hematopoietic cells.

PMID- 12239154
TI  - Biochemical characterization of PRV-1, a novel hematopoietic cell surface
      receptor, which is overexpressed in polycythemia rubra vera.
AB  - The cDNA for polycythemia rubra vera 1 (PRV-1), a novel hematopoietic receptor,
      was recently cloned by virtue of its overexpression in patients with polycythemia
      vera. PRV-1 is a member of the uPAR/CD59/Ly6 family of cell surface receptors,
      which share a common cysteine-rich domain and are tethered to the cell surface
      via a glycosylphosphatidylinositol (GPI) link. We have determined the intron-exon
      structure of the PRV1 gene and show that the locus is structurally intact in
      patients with polycythemia vera. Thus, PRV-1 overexpression in these patients is
      not due to rearrangement or structural alteration of the gene. Northern blot
      analysis detects multiple PRV-1 transcripts. Here we show that these transcripts
      arise from alternative polyadenylation and encode the same protein. Biochemical
      analysis reveals that PRV-1 is N-glycosylated and embedded in the cell membrane
      by a lipid anchor, like other members of this family. Moreover, PRV-1 is shed
      from the cell surface because soluble protein can be detected in cell
      supernatants. Fluorescence-activated cell sorting analysis of stably transfected
      cells revealed that PRV-1 is recognized by antibodies directed against the
      neutrophil antigen NB1/CD177. Flow cytometry of bone marrow and peripheral blood
      of both healthy donors and patients with polycythemia vera showed that PRV-1
      protein is expressed on myeloid cells of the granulocytic lineage. However,
      unlike the significant difference in PRV-1 expression observed on the mRNA level,
      the amount of PRV-1 protein on the cell surface is not consistently elevated in
      patients with polycythemia vera compared with healthy controls. Therefore,
      quantification of PRV-1 surface expression cannot be used for the diagnosis of
      polycythemia vera.

PMID- 12239155
TI  - Role of Cbfb in hematopoiesis and perturbations resulting from expression of the
      leukemogenic fusion gene Cbfb-MYH11.
AB  - Core-binding factor beta (CBFbeta) and CBFalpha2 form a heterodimeric
      transcription factor that plays an important role in hematopoiesis. The genes
      encoding either CBFbeta or CBFalpha2 are involved in chromosomal rearrangements
      in more than 30% of cases of acute myeloid leukemia (AML), suggesting that
      CBFbeta and CBFalpha2 play important roles in leukemogenesis. Inv(16)(p13;q22) is
      found in almost all cases of AML M4Eo and results in the fusion of CBFB with
      MYH11, the gene encoding smooth muscle myosin heavy chain. Mouse embryos
      heterozygous for a Cbfb-MYH11 knock-in gene lack definitive hematopoiesis, a
      phenotype shared by Cbfb(-/-) embryos. In this study we generated a Cbfb-GFP
      knock-in mouse model to characterize the normal expression pattern of Cbfbeta in
      hematopoietic cells. In midgestation embryos, Cbfbeta was expressed in
      populations enriched for hematopoietic stem cells and progenitors. This
      population of stem cells and progenitors was not present in mouse embryos
      heterozygous for the Cbfb-MYH11 knock-in gene. Together, these data suggest that
      Cbfb-MYH11 blocks embryonic hematopoiesis at the stem-progenitor cell level and
      that Cbfb is essential for the generation of hematopoietic stem and progenitor
      cells. In adult mice, Cbfbeta was expressed in stem and progenitor cells, as well
      as mature myeloid and lymphoid cells. Although it was expressed in erythroid
      progenitors, Cbfbeta was not expressed during the terminal stages of
      erythropoiesis. Our data indicate that Cbfb is required for myeloid and lymphoid
      differentiation; but does not play a critical role in erythroid differentiation.

PMID- 12239156
TI  - The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC.
AB  - Fanconi anemia is an autosomal recessive disorder characterized by aplastic
      anemia, cancer susceptibility, and cellular sensitivity to mitomycin C. The 6
      known Fanconi anemia gene products (FANCA, FANCC, FANCD2, FANCE, FANCF, and FANCG
      proteins) interact in a common pathway. The monoubiquitination and nuclear foci
      formation of FANCD2 are essential for the function of this pathway. FANCA, FANCC,
      FANCG, and FANCF proteins form a multisubunit nuclear complex (FA complex)
      required for FANCD2 monoubiquitination. Because FANCE and FANCC interact in vitro
      and FANCE is required for FANCD2 monoubiquitination, we reasoned that FANCE is a
      component of the FA complex in vivo. Here we demonstrate that retroviral
      transduction of Fanconi anemia subtype E (FA-E) cells with the FANCE cDNA
      restores the nuclear accumulation of FANCC protein, FANCA-FANCC complex
      formation, monoubiquitination and nuclear foci formation of FANCD2, and mitomycin
      C resistance. Hemagglutinin (HA)-tagged FANCE protein localizes diffusely in the
      nucleus. In normal cells, HA-tagged FANCE protein coimmunoprecipitates with
      FANCA, FANCC, and FANCG but not with FANCD2. Our data indicate that FANCE is a
      component of the nuclear FA complex in vivo and is required for the
      monoubiquitination of FANCD2 and the downstream events in the FA pathway.

PMID- 12239157
TI  - The antiapoptosis protein survivin is associated with cell cycle entry of normal
      cord blood CD34(+) cells and modulates cell cycle and proliferation of mouse
      hematopoietic progenitor cells.
AB  - The inhibitor of the apoptosis protein (IAP) survivin is expressed in
      proliferating cells such as fetal tissues and cancers. We previously reported
      that survivin is expressed and growth factor regulated in normal adult CD34(+)
      cells. Herein, we examined survivin expression in CD34(+) cells before and after
      cell cycle entry and demonstrate a role for survivin in cell cycle regulation and
      proliferation. Analysis of known human IAPs revealed that only survivin is
      cytokine regulated in CD34(+) cells. Survivin expression is coincident with cell
      cycle progression. Up-regulation of survivin by thrombopoietin (Tpo), Flt3 ligand
      (FL), and stem cell factor (SCF) occurred in underphosphorylated-retinoblastoma
      protein (Rb)(positive), Ki-67(negative), and cyclin D(negative) CD34(+) cells.
      Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR)
      and multivariate flow cytometry demonstrated that Tpo, SCF, and FL increase
      survivin mRNA and protein in quiescent G(0) CD34(+) cells without increasing Ki
      67 expression, indicating that cytokine-stimulated up-regulation of survivin in
      CD34(+) cells occurs during G(0), before cells enter G(1). Selective inhibition
      of the PI3-kinase/AKT and mitogen-activated protein kinase (MAPK(p42/44))
      pathways blocked survivin up-regulation by growth factors before arresting cell
      cycle. Retrovirus transduction of survivin-internal ribosome entry site-enhanced
      green fluorescent protein (survivin-IRES-EGFP) in primary mouse marrow cells
      increased granulocyte macrophage-colony-forming units (CFU-GM) by 1.7- to 6.2
      fold and the proportion of CFU-GM in S phase, compared to vector control. An
      antisense survivin construct decreased total and S-phase CFU-GM. These studies
      provide further evidence that survivin up-regulation by growth factors is not a
      consequence of cell cycle progression and strongly suggest that survivin is an
      important early event for cell cycle entry by CD34(+) cells.

PMID- 12239158
TI  - Sustained integrin ligation involves extracellular free sulfhydryls and
      enzymatically catalyzed disulfide exchange.
AB  - Studies have suggested a pivotal role for free sulfhydryls in platelet integrin
      function, and enzyme-mediated reduction of disulfide bonds on platelets has been
      implicated. The platelet fibrinogen receptor alpha(IIb)beta(3) is the best
      studied platelet integrin and serves as a model system for studying the structure
      function relation in this family of adhesion receptors. The demonstration of free
      sulfhydryls on the exofacial domain of purified alpha(IIb)beta(3), specifically
      in its activated conformation, prompted us to explore the potential for
      activation-dependent, enzymatically catalyzed thiol expression on intact
      platelets and the possible role of surface-associated protein disulfide isomerase
      (PDI) in alpha(IIb)beta(3) ligation. Using the membrane-impermeant sulfhydryl
      blocker para-chloromercuriphenyl sulfonate, the inhibitor of disulfide exchange
      bacitracin, and the monoclonal anti-PDI antibody RL90, we examined fibrinogen
      binding to alpha(IIb)beta(3) as well as ligation-induced allosteric changes in
      the conformation of alpha(IIb)beta(3). We sought to distinguish the possible
      involvement of disulfide exchange in agonist-induced platelet stimulation from
      its role in integrin ligation. Analysis of the role of free thiols in platelet
      aggregation suggested a thiol-independent initial ligation followed by a thiol
      dependent stabilization of binding. Flow cytometric analysis showed that
      sustained binding of fibrinogen, as well as expression of ligand-induced binding
      site epitopes and ligand-bound conformation, depended on free thiols and
      disulfide exchange. Expression of P-selectin was minimally affected, even with
      complete inhibition of alpha(IIb)beta(3) function. These data indicate that
      although agonist-induced platelet stimulation is independent of ecto-sulfhydryls,
      engagement of integrin alpha(IIb)beta(3) on the intact platelet depends totally
      on their enzymatically catalyzed surface expression.

PMID- 12239159
TI  - Junctional adhesion molecule-2 (JAM-2) promotes lymphocyte transendothelial
      migration.
AB  - The molecular mechanisms underlying lymphocyte extravasation remain poorly
      characterized. We have recently identified junctional adhesion molecule-2 (JAM
      2), and have shown that antibodies to JAM-2 stain high endothelial venules (HEVs)
      within lymph nodes and Peyer patches of adult mice. Here we show that mouse
      lymphocytes migrate in greater numbers across monolayers of endothelioma cells
      transfected with JAM-2. The significance of these findings to an understanding of
      both normal and pathologic lymphocyte extravasation prompted us to clone the
      human homologue of JAM-2. We herein demonstrate that an anti-JAM-2 antibody, or a
      soluble JAM-2 molecule, blocks the transmigration of primary human peripheral
      blood leukocytes across human umbilical vein endothelial cells expressing
      endogenous JAM-2. Furthermore, we show that JAM-2 is expressed on HEVs in human
      tonsil and on a subset of human leukocytes, suggesting that JAM-2 plays a central
      role in the regulation of transendothelial migration.

PMID- 12239160
TI  - Lack of alpha2-antiplasmin promotes pulmonary heart failure via overrelease of
      VEGF after acute myocardial infarction.
AB  - Identification of a novel therapy for prevention of sudden death by ischemic
      cardiac infarction is an area of intensive investigation. We here report that the
      mortality due to an experimental acute myocardial infarction (AMI) was markedly
      increased in mice deficient in alpha2-antiplasmin (alpha2-AP(-/-) mice) but not
      in mice deficient in other components acting in fibrinolysis (tissue-type PA,
      urokinase type PA, or plasminogen activator inhibitor-1) even if the infarct area
      in alpha2-AP(-/-) mice was not different from those in the other mice.
      Echocardiography showed in alpha2-AP(-/-) mice after AMI an overload of the right
      ventricle and that pulmonary permeability was increased. According to the
      experiments using explanted myocytes and vascular smooth muscle cells, it was
      found that the amount of secreted vascular endothelial cell growth factor (VEGF)
      in alpha2-AP(-/-) mice was markedly increased compared with that in wild-type
      mice. Finally, an injection of an anti-VEGF antibody decreased the mortality
      after AMI in alpha2-AP(-/-) mice. Plasmin cleaves extracellular matrix-bound VEGF
      to release a diffusible proteolytic fragment and is inactivated mainly by alpha2
      AP. Therefore, lack of alpha2-AP could markedly result in overrelease of VEGF by
      the continuous activation of plasmin because of AMI and could result in an acute
      cor pulmonale. Our results provide new aspects on the role of alpha2-AP and VEGF
      in the pathogenesis of cardiac events.

PMID- 12239161
TI  - Hemin induces neuroglobin expression in neural cells.
AB  - Neuroglobin is a newly identified vertebrate globin that binds O(2) and is
      expressed in cerebral neurons. We found recently that neuronal expression of
      neuroglobin is stimulated by hypoxia and ischemia and protects neurons from
      hypoxic injury. Here we report that, like hemoglobin and myoglobin, neuroglobin
      expression can also be induced by hemin. Induction was concentration dependent
      and time dependent, with maximal (about 4-fold) increases in neuroglobin mRNA and
      protein levels occurring with 50 microM hemin and at 8 to 24 hours. The inductive
      effect of hemin was attenuated by the protein kinase G inhibitor KT5823 and the
      soluble guanylate cyclase inhibitor LY83583, was mimicked by treatment with 8
      bromo-cyclic guanosine 3',5'-monophosphate, and was accompanied by a greater than
      10-fold increase in cGMP levels, suggesting that it is mediated through protein
      kinase G and soluble guanylate cyclase. In contrast, hypoxic induction of
      neuroglobin was blocked by the mitogen-activated protein kinase/extracellular
      signal-regulated kinase kinase inhibitor PD98059, indicating that hemin and
      hypoxia regulate neuroglobin expression by different mechanisms. These results
      provide evidence for regulation of neuroglobin expression by at least 2 signal
      transduction pathways.

PMID- 12239162
TI  - P2X(1)-mediated activation of extracellular signal-regulated kinase 2 contributes
      to platelet secretion and aggregation induced by collagen.
AB  - Adenosine triphosphate (ATP) and its stable analog, alpha,beta-methylene ATP,
      activate the platelet P2X(1) ion channel, causing a rapid Ca(++) influx. Here, we
      show that, in washed apyrase-treated platelets, alpha,beta-methylene ATP elicits
      reversible extracellular signal-regulated kinase 2 (ERK2) phosphorylation through
      a Ca(++)- and protein kinase C-dependent pathway. In contrast, high-performance
      liquid chromatography-purified adenosine diphosphate (ADP) did not trigger ERK2
      phosphorylation. alpha,beta-Methylene ATP also activated the ERK2 pathway in
      P2X(1)-transfected HEK293 cells but not in cells expressing mutated P2X(1)delL
      nonfunctional channels. Because ATP released from the dense granules during
      platelet activation contributes to platelet aggregation elicited by low doses of
      collagen, and because collagen causes ERK2 phosphorylation, we have investigated
      the role of P2X(1)-mediated ERK2 activation in these platelet responses. We found
      that the antagonism of P2X(1) with ADP or desensitization of this ion channel
      with alpha,beta-methylene ATP both resulted in impaired ERK2 phosphorylation, ATP
      secretion, and platelet aggregation induced by low concentrations of collagen (<
      or = 1 microg/mL) without affecting the minor early dense granule release.
      Selective MEK1/2 inhibition by U-0126 and Ca(++) chelation with EGTA
      (ethyleneglycoltetraacetic acid) behaved similarly, whereas the PKC inhibitor
      GF109203-X totally prevented collagen-induced secretion and ERK2 activation. In
      contrast, when elicited by high collagen concentrations (2 microg/mL), platelet
      aggregation and secretion no longer depended on P2X(1) or ERK2 activation, as
      shown by the lack of their inhibition by alpha,beta-methylene ATP or U-0126. We
      thus conclude that mild platelet stimulation with collagen rapidly releases ATP,
      which activates the P2X(1)-PKC-ERK2 pathway. This process enhances further
      degranulation of the collagen-primed granules allowing platelet aggregation to be
      completed.

PMID- 12239163
TI  - Evidence that alpha-synuclein functions as a negative regulator of Ca(++)
      dependent alpha-granule release from human platelets.
AB  - alpha-Synuclein has been implicated in the pathogenesis of Parkinson disease (PD)
      and related neurodegenerative disorders. More recently, it has been suggested to
      be an important regulatory component of vesicle transport in neuronal cells.
      alpha-Synuclein is also highly expressed in platelets and is loosely associated
      with the membrane of the secretory alpha-granules. However, the functional
      significance of these observations is unknown. In this study, the possible
      function of alpha-synuclein in vesicle transport, with particular regard to alpha
      granule release from the platelets, was investigated. The results showed that
      ionomycin- or thrombin-induced alpha-granule secretion was inhibited by exogenous
      alpha-synuclein addition in a dose-dependent manner. However, [(3)H]5-HT release
      from the dense granules and hexosaminidase release from the lysosomal granules
      were not affected. Two point mutants (A30P and A53T) found in some familial types
      of PD, in addition to beta-synuclein and alpha-synuclein112, effectively
      inhibited PF4 release from the alpha-granules. However, the deletion mutants,
      which completely lacked either the N-terminal region or the C-terminal tail, did
      not affect alpha-granule release. Interestingly, exogenously added alpha
      synuclein appeared to enter the platelets but did not change the Ca(++) level in
      the platelets at the resting state and the increase in the Ca(++) level on
      stimulation. Electron microscopy also supported that alpha-synuclein inhibits
      alpha-granule release. These results suggest that alpha-synuclein may function as
      a specific negative regulator of alpha-granule release in platelets.

PMID- 12239164
TI  - Molecular basis of quantitative factor V deficiency associated with factor V R2
      haplotype.
AB  - To investigate the molecular mechanisms of the quantitative factor V (FV)
      deficiency associated with the FV R2 haplotype, 4 missense mutations, Met385Thr,
      His1299Arg, Met1736Val, and Asp2194Gly, identified in the R2 haplotype allele,
      were analyzed by in vitro expression studies. The FV variant carrying all 4
      mutations showed a markedly lower steady-state expression level than wild-type FV
      because of low synthesis rate and impaired secretion of the mutant protein. The
      Asp2194Gly mutation was found to play a key role in the impaired secretion of the
      mutant FV by interfering with its transport from the endoplasmic reticulum to the
      Golgi complex. The deleterious effect of the Asp2194Gly mutation was shown to be
      dominant among the 4 mutations. The Met385Thr mutation and His1299Arg mutation
      had no effect on steady-state expression levels, but the secretion rates of the
      mutant proteins were moderately decreased by these mutations. The His1299Arg
      mutation partially impaired glycosylation in the C-terminal part of the B-domain
      of the mutant FV, which was supposed to affect the secretion rate, but not the
      steady-state expression level. It was also suggested that the Met385Thr mutation
      partially impairs posttranslational modification of the mutant FV without
      affecting the steady-state expression level. No deleterious effect of the
      Met1736Val mutation was observed in terms of expression and intracellular
      processing. Our in vitro data strongly suggest that the naturally existing R2
      haplotype mutant FV, which carries all 4 mutations, has the potential to result
      in quantitative FV deficiency in vivo owing to impaired expression of the mutant
      protein when the Asp2194Gly mutation is present.

PMID- 12239165
TI  - Biphasic transmittance waveform in the APTT coagulation assay is due to the
      formation of a Ca(++)-dependent complex of C-reactive protein with very-low
      density lipoprotein and is a novel marker of impending disseminated intravascular
      coagulation.
AB  - A decrease in light transmittance before clot formation, manifesting as a
      biphasic waveform (BPW) pattern in coagulation assays, was previously correlated
      with the onset of disseminated intravascular coagulation (DIC). In this study of
      1187 consecutive admissions to the intensive care unit, the degree of this change
      on admission predicts DIC better than D-dimer measurements. Additionally, the BPW
      preceded the time of DIC diagnosis by 18 hours, on average, in 56% (203 of 362)
      of DIC patients. The BPW is due to the rapid formation of a precipitate and
      coincident turbidity change on recalcification of plasma. The isolated
      precipitate contains very-low-density lipoprotein (VLDL) and C-reactive protein
      (CRP). The addition of CRP and Ca(++) to normal plasma also causes the
      precipitation of VLDL and IDL, but not LDL or HDL. The K(d) of the CRP/VLDL
      interaction is 340 nM, and the IC(50) for Ca(++) is 5.0 mM. In 15 plasmas with
      the BPW, CRP was highly elevated (77-398 microg/mL), and the concentration of
      isolated VLDL ranged from 0.082 to 1.32 mM (cholesterol). The turbidity change on
      recalcification correlates well with the calculated level of the CRP-VLDL
      complex. Clinically, the BPW better predicts for DIC than either CRP or
      triglyceride alone. The complex may have pathophysiological implications because
      CRP can be detected in the VLDL fraction from sera of patients with the BPW, and
      the VLDL fraction has enhanced prothrombinase surface activity. The complex has
      been designated lipoprotein complexed C-reactive protein.

PMID- 12239166
TI  - Heparin acts synergistically with interleukin-11 to induce STAT3 activation and
      in vitro osteoclast formation.
AB  - We have previously demonstrated that long-term heparin treatment causes
      cancellous bone loss in rats due in part to an increase in the number of
      osteoclasts lining the trabecular bone surface. In the present study, we
      investigated this phenomenon by examining the ability of heparin to
      synergistically enhance interleukin-11 (IL-11)-induced osteoclast formation.
      Treatment of murine calvaria and bone marrow cells with IL-11 was found to induce
      the formation of tartrate-resistant acid phosphatase-positive (TRAP(+))
      multinucleated cells (MNCs) in a dose-dependent fashion. No effect was seen when
      cocultures were treated with heparin alone. However, when cocultures were treated
      with both IL-11 and heparin, IL-11's ability to induce TRAP(+) MNC formation was
      enhanced 6-fold. In an attempt to resolve the mechanism responsible for this
      effect, we examined the ability of heparin to influence IL-11 signaling using
      murine calvaria cells. Heparin was found to enhance both IL-11-induced STAT3-DNA
      complex formation and transactivation without altering either STAT3 (signal
      transducer and activator of transcription-3) tyrosine or serine phosphorylation.
      Heparin was also found to enhance IL-11's ability to induce the expression of
      both receptor activator of nuclear factor-kappaB ligand (RANKL) and glycoprotein
      (gp) 130. When taken together, these findings suggest a plausible mechanism by
      which heparin may cause increased osteoclastogenesis and therefore bone loss when
      administered long-term.

PMID- 12239167
TI  - Creating space: an antigen-independent, CpG-induced peripheral expansion of naive
      and memory T lymphocytes in a full T-cell compartment.
AB  - Many of the mechanisms that govern T-cell homeostasis remain obscure. Here we
      report that repeated administration of synthetic oligodeoxynucleotides containing
      unmethylated cytosine-guanine motifs (CpG-ODN) into mice induces a systemic
      antigen-independent expansion of naive and memory T cells in a full T-cell
      compartment. Expansion of T cells was observed on both CD4(+) and CD8(+) T-cell
      subsets and was produced not by inducing the proliferation of the cells but by
      preventing their death. The antiapoptotic effects of CpG-ODN on T cells were
      observed against activation-induced death and growth factor withdrawal-mediated
      death. The ability of CpG-ODN to protect T cells from these forms of death was
      associated with the up-regulation of antiapoptotic gene products including c
      FLIP, bcl-xL, and, to some extent, bcl-2. The effect of CpG-ODN on naive and
      memory T cells required the expression of CD28 and was not dependent on the
      presence of B lymphocytes, suggesting that other antigen-presenting cells that
      respond to CpG-ODN, such as dendritic cells, may provide antiapoptotic signals to
      T cells in an antigen-independent but CD28/B7-dependent fashion. The present
      findings suggest that CpG-ODN can disrupt normal T-cell homeostasis not by acting
      as a mitogen but by preventing T-cell death that normally takes place as a
      mechanism to maintain steady-state levels of T cells. These findings support a
      potential means to expeditiously replenish and maintain the peripheral lymphocyte
      population after severe immunodepletion such as that which occurs in HIV-infected
      individuals and individuals undergoing cytoablative therapies.

PMID- 12239168
TI  - gp120-mediated induction of the MAPK cascade is dependent on the activation state
      of CD4(+) lymphocytes.
AB  - The capacity of the HIV-1 envelope glycoprotein gp120 to induce intracellular
      signals is thought to contribute to HIV-1 pathogenesis. Here, we report that
      gp120 binding resulted in activation of the mitogen-activated protein kinase
      (MAPK) in CD4(+) lymphocytes prestimulated through their T-cell receptor (TCR).
      However, gp120 did not activate this pathway in either freshly isolated quiescent
      T cells or nonproliferating CD4(+) lymphocytes prestimulated with the interleukin
      7 (IL-7) cytokine. This response was not solely dependent on proliferation per se
      because proliferating IL-7-prestimulated umbilical cord (UC)-derived T
      lymphocytes did not exhibit significant MAPK activation upon gp120 binding.
      Nevertheless, like peripheral blood lymphocytes, MAPK recruitment was induced by
      gp120 in UC T cells following TCR prestimulation. The lack of a gp120-mediated
      signaling response was not due to decreased gp120 receptor levels; CD4 expression
      was modified neither by IL-7 nor by TCR engagement, and high levels of functional
      CXCR4 were present on IL-7-treated lymphocytes. In addition to CD4 and CXCR4,
      recent evidence suggests that glycosphingolipids in raft microdomains serve as
      cofactors for HIV-1 fusion. The ganglioside GM1, a marker of rafts, was augmented
      in TCR-stimulated but not IL-7-stimulated T lymphocytes, and disruption of rafts
      inhibited gp120-induced signaling. Thus, stimulation of a mitogenic pathway by
      gp120 appears to require receptor binding in the context of membrane
      microdomains. These studies reveal a mechanism via which gp120 may differentially
      modulate the fate of activated and quiescent T cells in vivo.

PMID- 12239169
TI  - Dendritic cells for NK/LAK activation: rationale for multicellular immunotherapy
      in neuroblastoma patients.
AB  - Natural killer (NK)/lymphokine-activated killer (LAK) cell-based immunotherapy
      could be beneficial against major histocompatibility complex class I-negative
      tumor residual disease such as neuroblastoma (NB), provided that interleukin 2
      (IL-2) or surrogate nontoxic NK cell stimulatory factors could sustain NK cell
      activation and survival in vivo. Here we show that human monocyte-derived
      dendritic cells (MD-DCs) promote potent NK/LAK effector functions and long-term
      survival, circumventing the need for IL-2. This study demonstrates (1) the
      feasibility of differentiating granulocyte colony-stimulating factor-mobilized
      hematopoietic peripheral blood stem cells (PBSCs) into high numbers of functional
      MD-DCs and NK/LAK cells in a series of 12 children with stage 4 neuroblastoma
      (NB); (2) potent DC-mediated NK cell activation in autologous settings; (3) the
      reciprocal capacity of NK/LAK cells to turn immature DCs into maturing cells
      electively capable of triggering NK cell functions; and (4) the unique capacity
      of maturing DCs to sustain NK cell survival, superior to that achieved in IL-2.
      These data show a reciprocal interaction between DCs and NK/LAK cells, leading to
      the amplification of NK cell effector functions, and support the implementation
      of DC/NK cell-based immunotherapy for purging the graft and/or controlling
      minimal residual disease after autologous stem cell transplantation.

PMID- 12239170
TI  - Role for granulocyte colony-stimulating factor in the generation of human T
      regulatory type 1 cells.
AB  - Granulocyte colony-stimulating factor (G-CSF) may affect T-cell homeostasis by
      multiple mechanisms, inducing polarization of cytokine secretion, inhibition of T
      cell proliferation, and enhancement of T-cell apoptosis. We analyzed the
      production of interleukin-10 (IL-10) and transforming growth factor-beta1 (TGF
      beta1) by T cells from healthy volunteer donors treated with recombinant human G
      CSF. Highly purified CD4(+) T cells obtained before and after G-CSF
      administration (pre-G and post-G, respectively) were activated using the
      allogeneic mixed leukocyte reaction. Post-G CD4(+) T cells produced high levels
      of IL-10 but undetectable levels of IL-2 and IL-4, whereas the level of TGF-beta1
      release was comparable to that of pre-G CD4(+) T cells. Notably, post-G CD4(+) T
      cells proliferated poorly in response to alloantigens and to recall antigens and
      suppressed the proliferation of autologous CD4(+) T cells in a cell contact
      independent and an antigen-nonspecific manner. TGF-beta1 and IL-10 were not
      dispensable for post-G CD4(+) T cells to mediate suppression, as shown by
      neutralization studies. Compared with pre-G CD4(+) T cells, alloantigen-activated
      post-G CD4(+) T cells preferentially expressed markers associated with memory T
      cells, in conjunction with reduced levels of CD28 and CD62L. Collectively, these
      data demonstrate that CD4(+) T cells exposed to G-CSF in vivo acquire the
      properties of T regulatory (Tr) cells once triggered in vitro through the T-cell
      receptor, including a peculiar cytokine production profile (IL-10(++)TGF
      beta1(+)IL-2(low/-)IL-4(low/-)), an intrinsic low proliferative capacity, and a
      contact-independent suppression of antigen-driven proliferation. Tr cells
      generated ex vivo after exposure to G-CSF might be clinically relevant for
      transplantation medicine and for the treatment of human immune-mediated diseases.

PMID- 12239171
TI  - Aberrant DNA methylation of p57(KIP2) gene in the promoter region in lymphoid
      malignancies of B-cell phenotype.
AB  - The cyclin-dependent kinase inhibitor p57(KIP2) is thought to be a potential
      tumor suppressor gene (TSG). The present study examines this possibility. We
      found that the expression of p57(KIP2) gene is absent in various hematological
      cell lines. Exposing cell lines to the DNA demethylating agent 5-aza-2'
      deoxycytidine restored p57(KIP2) gene expression. Bisulfite sequencing analysis
      of its promoter region showed that p57(KIP2) DNA was completely methylated in
      cell lines that did not express the p57(KIP2) gene. Thus, DNA methylation of its
      promoter might lead to inactivation of the p57(KIP2) gene. DNA methylation of
      this region is thought to be an aberrant alteration, since DNA was not methylated
      in normal peripheral blood mononuclear cells or in reactive lymphadenitis.
      Methylation-specific polymerase chain reaction analysis found frequent DNA
      methylation of the p57(KIP2) gene in primary diffuse large B-cell lymphoma
      (54.9%) and in follicular lymphoma (44.0%), but methylation was infrequent in
      myelodysplastic syndrome and adult T-cell leukemia (3.0% and 2.0%, respectively).
      These findings directly indicate that the profile of the p57(KIP2) gene
      corresponds to that of a TSG.

PMID- 12239172
TI  - Characterization of hyaluronan synthase expression and hyaluronan synthesis in
      bone marrow mesenchymal progenitor cells: predominant expression of HAS1 mRNA and
      up-regulated hyaluronan synthesis in bone marrow cells derived from multiple
      myeloma patients.
AB  - Hyaluronan (HA) is suggested to play a role in the pathophysiology of multiple
      myeloma. To further investigate the role of HA in this disease, we examined
      hyaluronan synthase (Has) gene expression and HA production in bone marrow
      mesenchymal progenitor cells (bmMPCs) derived from multiple myeloma patients. The
      relative abundance of mRNA for each HAS gene was determined using competitive
      reverse transcription-polymerase chain reaction (cRT-PCR), whereas HA production
      was detected by fluorophore-assisted carbohydrate electrophoresis (FACE). We
      determined the basal expression of Has isoforms in myeloma bmMPCs and then
      compared this expression with expression in healthy donor bmMPCs. Of the 3 Has
      isoforms, Has1 mRNA was expressed predominantly in myeloma bmMPCs, with
      expression 7.6-fold greater than Has2. Compared with normal bmMPCs, Has1 mRNA
      expression was 20-fold greater in myeloma bmMPCs. Normal bmMPCs predominantly
      expressed Has2 mRNA (8.2-fold greater than myeloma bmMPCs). Upon coculture of
      myeloma bmMPCs with plasma cells, Has1 transcript was strongly attenuated. FACE
      results show that myeloma bmMPCs synthesize 5.7-fold more HA than those from
      healthy donors. These data suggest that myeloma bmMPCs could be an important
      component of the myeloma pathophysiology in vivo by their increased expression of
      extracellular matrix (ECM) components relevant to plasma cell growth and
      survival.

PMID- 12239173
TI  - Response to histone deacetylase inhibition of novel PML/RARalpha mutants detected
      in retinoic acid-resistant APL cells.
AB  - Resistance to all-trans retinoic acid (ATRA) remains a clinical problem in the
      treatment of acute promyelocytic leukemia (APL) and provides a model for the
      development of novel therapies. Molecular alterations in the ligand-binding
      domain (LBD) of the PML/RARalpha fusion gene that characterizes APL constitute
      one mechanism of acquired resistance to ATRA. We identified missense mutations in
      PML/RARalpha from an additional ATRA-resistant patient at relapse and in a novel
      ATRA-resistant cell line, NB4-MRA1. These cause altered binding to ligand and
      transcriptional coregulators, leading to a dominant-negative block of
      transcription. These mutations are in regions of the LBD that appear to be
      mutational hot spots occurring repeatedly in ATRA-resistant APL patient cells. We
      evaluated whether histone deacetylase (HDAC) inhibition could overcome the
      effects of these mutations on ATRA-induced gene expression. Cotreatment with ATRA
      and TSA restored RARbeta gene expression in NB4-MRA1 cells, whose PML/RARalpha
      mutation is in helix 12 of the LBD, but not in an APL cell line harboring the
      patient-derived PML/RARalpha mutation, which was between helix 5 and 6.
      Furthermore, ATRA combined with TSA increases histone 4 acetylation on the
      RARbeta promoter only in NB4-MRA1 cells. Consistent with these results, the
      combined treatment induces differentiation of NB4-MRA1 only. Thus, the ability of
      an HDAC inhibitor to restore ATRA sensitivity in resistant cells may depend on
      their specific molecular defects. The variety of PML/RARalpha mutations arising
      in ATRA-resistant patients begins to explain how APL patients in relapse may
      differ in response to transcription therapy with HDAC inhibitors.

PMID- 12239174
TI  - CXCR4-SDF-1 signaling is active in rhabdomyosarcoma cells and regulates
      locomotion, chemotaxis, and adhesion.
AB  - We hypothesized that the CXC chemokine receptor-4 (CXCR4)-stromal-derived factor
      1 (SDF-1) axis may be involved in metastasis of CXCR4(+) tumor cells into the
      bone marrow and lymph nodes, which secrete the alpha-chemokine SDF-1. To explore
      this hypothesis, we phenotyped by fluorescence-activated cell sorter analysis
      various human tumor cell lines for expression of CXCR4 and found that it was
      highly expressed on several rhabdomyosarcoma (RMS) cell lines. We also observed
      that cell lines derived from alveolar RMS, which is characterized by recurrent
      PAX3- and PAX7-FKHR gene fusions and is associated with a poor prognosis,
      expressed higher levels of CXCR4 than lines derived from embryonal RMS.
      Furthermore, transfer of a PAX3-FKHR gene into embryonal RMS cell activates CXCR4
      expression. Because alveolar RMS frequently metastasizes to the bone marrow and
      lymph nodes, it seems that the CXCR4-SDF-1 axis could play an important role in
      this process. These findings prompted us to determine whether SDF-1 regulates the
      metastatic behavior of RMS cells. Accordingly, we found that, although SDF-1 did
      not affect proliferation or survival of these cell lines, it induced in several
      of them (1) phosphorylation of mitogen-activated protein kinase p42/44; (2)
      locomotion; (3) directional chemotaxis across membranes covered by laminin,
      fibronectin, or Matrigel; (4) adhesion to laminin, fibronectin, and endothelial
      cells; and (5) increased MMP-2 and diminished tissue inhibitors of
      metalloproteinases secretion. The small-molecule CXCR4-specific inhibitor, T140,
      effectively blocked the in vitro responses of RMS cells to SDF-1. On the basis of
      these observations we suggest that the CXCR4-SDF-1 axis may play an important
      role in tumor spread and metastasis of RMS cells to bone marrow and that
      molecular strategies aimed at inhibiting this axis could thus prove to be useful
      therapeutic measures.

PMID- 12239175
TI  - Role of PI3-kinase-dependent Bad phosphorylation and altered transcription in
      cytokine-mediated neutrophil survival.
AB  - Phosphoinositide 3-kinase (PI3-kinase)-dependent phosphorylation of the
      proapoptotic Bcl-2 family member Bad has been proposed as an important regulator
      of apoptotic cell death. To understand the importance of this pathway in
      nontransformed hematopoietic cells, we have examined the effect of survival
      cytokines on PI3-kinase activity and Bad expression and phosphorylation status in
      human neutrophils. Granulocyte macrophage-colony-stimulating factor (GM-CSF) and
      tumor necrosis factor-alpha (TNF-alpha) both reduced the rate of apoptosis in
      neutrophils cultured in vitro for 20 hours. Coincubation with the PI3-kinase
      inhibitor LY294002, which in parallel experiments abolished GM-CSF-primed, fMLP
      stimulated superoxide anion production and GM-CSF-stimulated PtdIns(3,4,5)P(3)
      accumulation, inhibited the GM-CSF and TNF-alpha survival effect. In contrast,
      the MAP kinase kinase (MEK1/2) inhibitor PD98059 and the protein kinase A
      inhibitor H-89 had only a marginal effect on GM-CSF-mediated neutrophil survival.
      GM-CSF substantially increased Bad phosphorylation at Ser112 and Ser136 and
      increased the cytosolic accumulation of Bad. GM-CSF also regulated Bad at a
      transcription level with a marked decrease in mRNA levels at 4 hours. TNF-alpha
      caused a biphasic effect on the rate of morphologic apoptosis, which corresponded
      to an early increase, and a late inhibition, of Bad mRNA levels. LY294002
      inhibited GM-CSF- and TNF-alpha-mediated changes in Bad phosphorylation and mRNA
      levels. These data suggest that the survival effect of GM-CSF and TNF-alpha in
      neutrophils is caused by a PI3-kinase-dependent phosphorylation and cytosolic
      translocation of Bad, together with an inhibition of Bad mRNA levels. This has
      important implications for the regulation of neutrophil apoptosis in vivo.

PMID- 12239176
TI  - Iron transporter Nramp2/DMT-1 is associated with the membrane of phagosomes in
      macrophages and Sertoli cells.
AB  - Nramp2 (DMT1) is a pH-dependent divalent cation transporter that acts as the
      transferrin-independent iron uptake system at the intestinal brush border and
      also transports iron released from transferrin across the membrane of acidified
      endosomes. In this study, RAW264.7 macrophages and 2 independently derived murine
      Sertoli cells lines, TM4 and 15P-1, were used to further study the subcellular
      localization of Nramp2/DMT1 in phagocytic cells, including possible recruitment
      to the phagosomal membrane. Nramp2/DMT1 was localized primarily to the EEA1
      positive recycling endosome compartment, with some overlapping staining with
      Lamp1-positive late endosomes. After phagocytosis, immunofluorescence analysis
      and in vitro biochemical studies using purified latex bead-containing phagosomes
      indicated Nramp2/DMT1 recruitment to the membrane of Lamp1, cathepsin D, and rab7
      positive phagosomes. Nramp2/DMT1 was also found associated with erythrocyte
      containing phagosomes in RAW macrophages and with the periphery of sperm
      containing phagosomes in Sertoli cells. These results suggest that, as for the
      macrophage-specific Nramp1 protein, Nramp2/DMT1 may transport divalent metals
      from the phagosomal space.

PMID- 12239177
TI  - Hypoxia-inducible erythropoietin gene expression in human neuroblastoma cells.
AB  - Two human neuroblastoma (NB) cell lines, SH-SY5Y and Kelly, were found to express
      the gene for erythropoietin (EPO) in an oxygen (O(2))-dependent manner. However,
      NB cells had maximal production of EPO with lower partial pressure of O(2) values
      than the well-characterized hepatoma cell line HepG2. This maximal EPO expression
      was preceded by accumulation of the O(2)-sensitive alpha subunit of the
      heterodimeric transcription-factor complex hypoxia-inducible factor 1 (HIF-1).
      Western blot analysis revealed that the amount of the beta subunit of HIF-1,
      identical to aryl hydrocarbon receptor nuclear translocator 1 (ARNT1), and the
      homolog ARNT2 increased in nuclear extracts from SH-SY5Y cells exposed to anoxia.
      In neuronal cells, ARNT1 and ARNT2 can form a heterodimer with HIF-1alpha,
      generating a functional HIF-1 complex. Using the hypoxia response element of the
      human EPO enhancer, we conducted electrophoretic mobility shift assays that
      showed accumulation and binding of HIF-1 complexes containing both ARNT1 and
      ARNT2 in NB cells. In addition to the HIF-1 complex, hepatocyte nuclear factor
      4alpha (HNF4alpha) was found to be indispensable for hypoxia-induced EPO gene
      expression in hepatoma cells. Western blot analysis and polymerase chain reaction
      assessment showed that NB cells express neither HNF4alpha nor the splicing
      variant HNF4alpha7 and thus express EPO in an HNF4alpha-independent manner.
      Together, SH-SY5Y and Kelly cells may provide a new in vitro model for studying
      the mechanism of tissue-specific, hypoxia-inducible EPO gene expression.

PMID- 12239178
TI  - A splicing alteration of 4.1R pre-mRNA generates 2 protein isoforms with distinct
      assembly to spindle poles in mitotic cells.
AB  - The C-terminal region of erythroid cytoskeletal protein 4.1R, encoded by exons 20
      and 21, contains a binding site for nuclear mitotic apparatus protein (NuMA), a
      protein needed for the formation and stabilization of the mitotic spindle. We
      have previously described a splicing mutation of 4.1R that yields 2 isoforms:
      One, CO.1, lacks most of exon 20-encoded peptide and carries a missense C
      terminal sequence. The other, CO.2, lacks exon 20-encoded C-terminal sequence,
      but retains the normal exon 21-encoded C-terminal sequence. Knowing that both
      shortened proteins are expressed in red cells and assemble to the membrane
      skeleton, we asked whether they would ensure 4.1R mitotic function in dividing
      cells. We show here that CO.2, but not CO.1, assembles to spindle poles, and
      colocalizes with NuMA in erythroid and lymphoid mutated cells, but none of these
      isoforms interact with NuMA in vitro. In microtubule-destabilizing conditions,
      again only CO.2 localizes to the centrosomes. These data suggest that the
      stability of 4.1R association with centrosomes requires an intact C-terminal end,
      either for a proper conformation of the protein, for a direct binding to an
      unknown centrosome-cytoskeletal network, or for both. We also found that 4.1G, a
      ubiquitous homolog of 4.1R, is present in mutated as well as control cells and
      that its C-terminal region binds efficiently to NuMA, suggesting that in fact
      mitotic spindles host a mixture of the two 4.1 family members. These findings led
      to the postulate that the coexpression at the spindle poles of 2 related
      proteins, 4.1R and 4.1G, might reflect a functional redundancy in mitotic cells.

PMID- 12239179
TI  - Frequency and load of hepatitis B virus DNA in first-time blood donors with
      antibodies to hepatitis B core antigen.
AB  - The objective of this study was to determine the frequency and load of hepatitis
      B virus (HBV) DNA in anti-HBc-positive first-time blood donors; it was designed
      to contribute to determining whether anti-HBc screening of blood donations might
      reduce the residual risk of posttransfusion HBV infection. A total of 14 251
      first-time blood donors were tested for anti-HBc using a microparticle enzyme
      immunoassay; positive results were confirmed by a second enzyme-linked
      immunosorbent assay (ELISA). For the detection of HBV DNA from plasma samples, we
      developed a novel and highly sensitive real-time polymerase chain reaction (PCR)
      assay. The 95% detection limit of the method amounted to 27.8 IU/mL, consistent
      with the World Health Organization (WHO) international standard for HBV DNA. A
      total of 216 blood donors (1.52%) tested anti-HBc-positive in both tests, and 205
      of them (16 HBsAg(+), 189 HBsAg(-)) were tested for HBV DNA. In 14 (87.5%) of the
      HBsAg-positive blood donors, HBV DNA was repeatedly detected, and in 3 (1.59%) of
      the HBsAg-negative donors, HBV DNA was also found repeatedly. In the 3 HBV DNA
      positive, HBsAg-negative cases, anti-HBe and anti-HBs (> 100 IU/L) were also
      detectable. HBV DNA in HBsAg-negative as well as HBsAg-positive samples was seen
      at a low level. Thus, HBV DNA is sometimes found in HBsAg-negative, anti-HBc
      positive, and anti-HBs-positive donors. Retrospective studies on regular blood
      donors and recipients are necessary to determine the infection rate due to those
      donations. Routine anti-HBc screening of blood donations could probably prevent
      some transfusion-transmitted HBV infections.

PMID- 12239180
TI  - Interleukin 7 worsens graft-versus-host disease.
AB  - Impaired immune reconstitution has moved to the forefront of clinical problems
      limiting progress in allogeneic bone marrow transplantation (BMT). The
      identification of therapies that can enhance immune reconstitution by increasing
      thymopoiesis is critical to solving this problem. Interleukin 7 (IL-7) is the
      most potent thymopoietic cytokine identified thus far. To study the effects of IL
      7 on immune reconstitution and graft-versus-host disease (GVHD) following
      allogeneic BMT, we administered recombinant human IL-7 (rhIL-7) in a murine
      parent into an F1 model. Results showed that rhIL-7 therapy lowered the
      "threshold" T-cell dose required to induce both clinical signs of GVHD as well as
      lethal GVHD. Histologic analysis of GVHD target tissues revealed that rhIL-7
      increased the degree of inflammation and tissue damage observed at all T-cell
      doses studied, but did not change the pattern of organs affected or the
      histologic appearance of the GVHD within target organs. In addition, we evaluated
      the capacity for rhIL-7 to enhance thymopoiesis in the setting of allogeneic T
      cell-depleted (TCD) and T-cell-replete BMT. We observed that rhIL-7 therapy
      enhanced thymic function in TCD allogeneic BM transplant recipients, but not in
      animals that received even modest doses of T cells presumably due to thymic
      toxicity of the graft-versus-host reaction. Thus, caution must be exercised as IL
      7 is developed clinically as an immunorestorative agent for use in the setting of
      allogeneic BMT. These results suggest that use of IL-7 should be limited to the
      setting of TCD BMT to obtain the greatest benefit on immune competence with the
      least toxicity.

PMID- 12239181
TI  - Cytokine and chemokine profiles in autologous graft-versus-host disease (GVHD):
      interleukin 10 and interferon gamma may be critical mediators for the development
      of autologous GVHD.
AB  - Administration of the immunosuppressive drug cyclosporine A (CsA) following
      autologous stem cell transplantation paradoxically elicits a systemic autoimmune
      syndrome resembling graft-versus-host disease (GVHD). This syndrome, termed
      autologous GVHD, is associated with autoreactive CD8(+) T cells that recognize
      major histocompatibility complex (MHC) class II determinants in association with
      a peptide from the invariant chain. To investigate the potential role of
      cytokines and chemokines in autologous GVHD, interleukin 2 (IL-2), IL-4, IL-10,
      interferon gamma (IFN-gamma), and macrophage inflammatory protein-1alpha (MIP
      1alpha) gene expression in peripheral blood mononuclear cells (PBMCs) was
      determined in 36 patients treated with CsA following transplantation and
      correlated with the induction of cytolytic activity against autologous
      phytohemagglutinin-stimulated lymphocytes (PHA-blasts) and the breast cancer cell
      line (T47D). The determination of gene expression by real-time polymerase chain
      reaction (PCR) revealed that IL-10 mRNA levels by PBMCs in patients with
      autologous GVHD were 29-fold higher than in healthy individuals. IFN-gamma (4
      fold), IL-2 (3-fold), and MIP-1alpha (44-fold) mRNA levels were also increased in
      GVHD-induced patients compared with healthy individuals. The ability of PBMCs to
      lyse autologous PHA-blasts and T47D tumor cells exhibited an identical temporal
      relationship with expression of IL-10 and IFN-gamma during autologous GVHD.
      Moreover, the susceptibility to autologous GVHD as assessed in 75 patients was
      significantly associated with the IL-10(-1082) G/G polymorphic alleles, allelic
      variants in the promoter region that govern IL-10 production. These findings
      indicate that IL-10 may play an unexpected but critical role in autologous GVHD
      and could be utilized to enhance a graft-versus-tumor effect after
      transplantation. Interestingly, polymorphisms in the IL-10 promoter region may
      also explain differences in the susceptibility of patients to autologous GVHD
      induction.

PMID- 12239182
TI  - V(H) gene analysis of splenic marginal zone lymphomas reveals diversity in
      mutational status and initiation of somatic mutation in vivo.
AB  - Tumors of the splenic marginal zone can present in spleen or blood. The
      maturational status of the neoplastic B cells from each site appears
      heterogeneous, with either unmutated or mutated variable-region heavy chain
      (V(H)) genes. To determine an influence of tissue location, we assessed matched
      blood and splenic tumor cells from 4 patients and found them identical. However,
      one patient with unmutated V(H) genes in blood and spleen developed a clonally
      related diffuse large B-cell lymphoma in the chest wall. Strikingly, this
      subclone had undergone significant somatic mutation, with clear intraclonal
      heterogeneity. To our knowledge, this is the first case of a B-cell tumor showing
      initiation of somatic mutation in vivo. The finding emphasizes that the tissue
      microenvironment can influence tumor cell behavior and possibly affect disease
      progression. Importantly, because several replacement mutations were located
      within or close to the complementarity-determining regions (CDRs), it raises the
      question of a role for antigen in driving tumor growth.

PMID- 12239183
TI  - Placental/umbilical cord blood for unrelated-donor bone marrow reconstitution:
      relevance of nucleated red blood cells.
AB  - Placental/umbilical cord blood (PCB) is a source of hematopoietic stem cells for
      bone marrow reconstitution. Engraftment speed and survival are related to the
      total nucleated cell (TNC) dose of the graft. This study explored the possible
      influence on engraftment of nucleated red blood cells (NRBCs) in the graft.
      Automated hematology analyzers were used to enumerate TNCs. NRBCs were counted by
      visual examination or by using an automated analyzer. Hematopoietic progenitor
      cells were enumerated as either colony-forming cells or CD34(+) cells. Transplant
      centers reported on transplant outcome in 1112 patients given PCB grafts through
      September 2001. NRBCs correlated with progenitor cell numbers. Both white blood
      cell and NRBC dose were independently predictive of myeloid engraftment speed.
      Because NRBC dose predicted engraftment speed, inclusion of NRBCs in the TNC
      count does not reduce the effectiveness of the prefreezing TNC count as an index
      of the quality of a PCB unit as a graft. The correlation between the number of
      NRBCs and the number of hematopoietic progenitor cells probably reflects the
      involvement of early stem cells in erythroid responses.

PMID- 12239184
TI  - Evidence that the number of hematopoietic stem cells per animal is conserved in
      mammals.
AB  - Humans and larger mammals require more blood cells per lifetime than mice because
      of their larger size and longer life expectancy. To investigate this evolutionary
      adaptation, we calculated the total number of nucleated marrow cells (NMCs) per
      cat, observing the distribution of (59)Fe to marrow, then multiplied this value
      (1.9 +/- 0.9 x 10(10) [mean +/- SD]) times the frequency of feline hematopoietic
      stem cells (HSCs) (6 HSCs/10(7) NMCs) to derive the total number of HSCs per cat
      (11 400 +/- 5400). Surprisingly, when the total number of HSCs per mouse was
      calculated with a similar experimental and computational approach, the value was
      equivalent. These data imply that the output of differentiated cells per feline
      HSC must vastly exceed that of murine HSCs. Furthermore, if the total number of
      human HSCs were also equivalent to the total number of HSCs in cat and mouse, the
      frequency of human HSCs would be 0.7 to 1.5 HSCs/10(8) NMCs, a frequency that is
      20-fold less than estimated by the NOD/SCID repopulating assay.

PMID- 12239188
TI  - Is there a causal association between suicide rates and the political leanings of
      government?

PMID- 12239185
TI  - Phagocytosing neutrophils down-regulate the expression of chemokine receptors
      CXCR1 and CXCR2.
AB  - CXC chemokines play a central role in regulation of neutrophil activation and
      chemotaxis. Because the chemotactic responses of neutrophils are impaired after
      phagocytosis, we explored the effect of phagocytic stimuli on the expression of
      interleukin-8 (IL-8) receptors, CXCR1 and CXCR2, in human neutrophils. After
      phagocytosis of opsonized yeast, the expression of CXCR1 and CXCR2 was
      substantially down-regulated and was accompanied by reduced Ca(++) responses to
      corresponding ligands, IL-8 and neutrophil-activating peptide-2 (NAP-2). The
      levels of CXCR1 and CXCR2 mRNA were constant during phagocytic stimulation of
      neutrophils. Confocal microscopy revealed that CXCR reduction was not via
      internalization. Metalloproteinase inhibitor, 1,10-phenantroline, prevented the
      reduction of CXCRs induced by phagocytosis, indicating that proteolytic
      degradation may be responsible for down-regulation. These observations suggest
      that down-regulation of CXCR expression may substantially reduce the
      responsiveness of phagocytosing neutrophils to CXC chemokines.

PMID- 12239189
TI  - Mortality and political climate: how suicide rates have risen during periods of
      Conservative government, 1901-2000.

PMID- 12239190
TI  - How exactly do politics play a part in determining health? New perspectives on an
      age old issue.

PMID- 12239191
TI  - Political regime and suicide: some relevant variables to be considered.

PMID- 12239192
TI  - The science and art of molecular epidemiology.

PMID- 12239193
TI  - Molecular biomarkers in studies on environmental cancer.

PMID- 12239194
TI  - Health for all in the new millennium.

PMID- 12239195
TI  - Traditional healers, still part of the community health systems in the Andes.

PMID- 12239196
TI  - Incomplete overlapping of biological, clinical, and environmental information in
      molecular epidemiological studies: a variety of causes and a cascade of
      consequences.

PMID- 12239197
TI  - Ethics in epidemiology and public health II. Applied terms.

PMID- 12239198
TI  - Implementation of a new health system in Colombia: is this favourable for health
      determinants?

PMID- 12239199
TI  - Developing a multi-disciplinary public health specialist workforce: training
      implications of current UK policy.

PMID- 12239200
TI  - Health and demographic characteristics of respondents in an Australian national
      sexuality survey: comparison with population norms.
AB  - STUDY OBJECTIVE: To assess the representativeness of survey participants by
      systematically comparing volunteers in a national health and sexuality survey
      with the Australian population in terms of self reported health status (including
      the SF-36) and a wide range of demographic characteristics. DESIGN: A cross
      sectional sample of Australian residents were compared with demographic data from
      the 1996 Australian census and health data from the 1995 National Health Survey.
      SETTING: The Australian population. PARTICIPANTS: A stratified random sample of
      adults aged 18-59 years drawn from the Australian electoral roll, a compulsory
      register of voters. Interviews were completed with 1784 people, representing 40%
      of those initially selected (58% of those for whom a valid telephone number could
      be located). MAIN RESULTS: Participants were of similar age and sex to the
      national population. Consistent with prior research, respondents had higher
      socioeconomic status, more education, were more likely to be employed, and less
      likely to be immigrants. The prevalence estimates, means, and variances of self
      reported mental and physical health measures (for example, SF-36 subscales,
      women's health indicators, current smoking status) were similar to population
      norms. CONCLUSIONS: These findings considerably strengthen inferences about the
      representativeness of data on health status from volunteer samples used in health
      and sexuality surveys.

PMID- 12239201
TI  - Interrelations between three proxies of health care need at the small area level:
      an urban/rural comparison.
AB  - STUDY OBJECTIVE: To examine the relations between geographical variations in
      mortality, morbidity, and deprivation at the small area level in the south west
      of England and to assess whether these relations vary between urban and rural
      areas. DESIGN: A geographically based cross sectional study using 1991 census
      data on premature limiting long term illness (LLTI) and socioeconomic
      characteristics, and 1991-1996 data on all cause premature mortality. The
      interrelations between the three widely used proxies of health care need are
      examined using correlation coefficients and scatterplots. The distribution of
      standardised LLTI residuals from a regression analysis on mortality are mapped
      and compared with the distribution of urban and rural areas. Multilevel Poisson
      modelling investigates whether customised deprivation profiles improve upon a
      generic deprivation index in explaining the spatial variation in morbidity and
      mortality after controlling for age and sex. These relations are examined
      separately for urban, fringe, and rural areas. SETTING: Nine counties in the
      south west of England. PARTICIPANTS: Those aged between 0-64 who reported having
      a LLTI in the 1991 census, and those who died during 1991-1996 aged 0-74. MAIN
      RESULTS: Relations between both health outcomes and generic deprivation indices
      are stronger in urban than rural areas. The replacement of generic with
      customised indices is an improvement in all area types, especially for LLTI in
      rural areas. The relation between mortality and morbidity is stronger in urban
      than rural areas, with levels of LLTI appearing to be greater in rural areas than
      would be predicted from mortality rates. Despite the weak direct relations
      between mortality and morbidity, there are strong relations between the
      customised deprivation indices computed to predict these outcomes in all area
      types. CONCLUSIONS: The improvement of the customised deprivation indices over
      the generic indices, and the similarity between the mortality and morbidity
      customised indices within area types highlights the importance of modelling urban
      and rural areas separately. Stronger relations between mortality and morbidity
      have been revealed at the local authority level in previous research providing
      empirical evidence that the inadequacy of mortality as a proxy for morbidity
      becomes more marked at lower levels of aggregation, especially in rural areas.
      Higher levels of LLTI than expected in rural areas may reflect different
      perceptions or differing patterns of illness. The stronger relations between the
      three proxies in urban than rural areas suggests that the choice of indicator
      will have less impact in urban than rural areas and strengthens the argument to
      develop better measures of health care need in rural areas.

PMID- 12239202
TI  - Sampling variability of the Kunst-Mackenbach relative index of inequality.
AB  - STUDY OBJECTIVE: To derive methods of calculating confidence limits for the
      relative index of inequality, defined by Kunst and Mackenbach as a measure of the
      influence of socioeconomic status on an adverse health index, such as mortality
      rate. The methods may be used for a health outcome recorded on a continuous
      scale, as a Poisson count or as a binomial variable. RESULTS AND CONCLUSION: The
      confidence limits depend on the sampling variability of both the mean mortality
      rate and the slope of the regression line of mortality on the socioeconomic
      status scale variable. The best method for a continuous health outcome is based
      on Fieller's theorem but a good approximation is obtained by substituting the
      confidence limits for the slope of the regression line into the formula for the
      calculation of the index, or by using the variance of the logarithmic transform
      of the index. The last method is the most appropriate for the construction of
      significance tests comparing indices. The mortality rates may show statistically
      significant departure from linearity, while not suggesting that a linear relation
      is inappropriate, and the main decision is whether to base the confidence limits
      on the conventional standard error of the slope derived from the regression
      analysis or whether to use the standard deviation of the estimates of mortality
      rates.

PMID- 12239203
TI  - Suicide and political regime in New South Wales and Australia during the 20th
      century.
AB  - STUDY OBJECTIVE: Australia has had a two party parliamentary political system for
      most of the period since its Federation in 1901, dominated either by a social
      democratic (Labor) or a conservative ideological perspective. This paper
      investigates whether such political differences at Federal and State levels have
      influenced suicide rates in the state of New South Wales (NSW) for the period
      1901-1998. DESIGN: Federal government type, NSW State government type, and
      combinations of both Federal and NSW State government type were examined. Poisson
      regression models were stratified by sex and controlled for the effects of age,
      annual change in gross domestic product, sedative availability, drought, and both
      world wars. RESULTS: When both Federal and NSW State governments were
      conservative the relative risk of suicide for NSW men was 1.17 (p<0.001) and for
      women 1.40 (p<0.001) compared with both governments being Labor (1.00). A
      statistically significant linear trend (p<0.001) in suicide risk was evident
      across the continuum of Federal/State government combinations, from both Labor
      (lowest), to mixed (intermediate), to both conservative (highest). CONCLUSION:
      Significantly higher suicide risk was associated with conservative government
      tenures compared with social democratic incumbents. Results are discussed in
      terms of the differences underpinning conservative and social democratic
      government programme ideology, and their relevance to Durkheim's theories of
      suicide, social regulation, and integration.

PMID- 12239204
TI  - Short-term effects of particulate air pollution on cardiovascular diseases in
      eight European cities.
AB  - STUDY OBJECTIVE: As part of the APHEA project this study examined the association
      between airborne particles and hospital admissions for cardiac causes (ICD9 390
      429) in eight European cities (Barcelona, Birmingham, London, Milan, the
      Netherlands, Paris, Rome, and Stockholm). All admissions were studied, as well as
      admissions stratified by age. The association for ischaemic heart disease (ICD9
      410-413) and stroke (ICD9 430-438) was also studied, also stratified by age.
      DESIGN: Autoregressive Poisson models were used that controlled for long term
      trend, season, influenza epidemics, and meteorology to assess the short-term
      effects of particles in each city. The study also examined confounding by other
      pollutants. City specific results were pooled in a second stage regression to
      obtain more stable estimates and examine the sources of heterogeneity. MAIN
      RESULTS: The pooled percentage increases associated with a 10 micro g/m(3)
      increase in PM(10) and black smoke were respectively 0.5% (95% CI: 0.2 to 0.8)
      and 1.1% (95% CI: 0.4 to 1.8) for cardiac admissions of all ages, 0.7% (95% CI:
      0.4 to 1.0) and 1.3% (95% CI: 0.4 to 2.2) for cardiac admissions over 65 years,
      and, 0.8% (95% CI: 0.3 to 1.2) and 1.1% (95% CI: 0.7 to 1.5) for ischaemic heart
      disease over 65 years. The effect of PM(10) was little changed by control for
      ozone or SO(2), but was substantially reduced (CO) or eliminated (NO(2)) by
      control for other traffic related pollutants. The effect of black smoke remained
      practically unchanged controlling for CO and only somewhat reduced controlling
      for NO(2). CONCLUSIONS: These effects of particulate air pollution on cardiac
      admissions suggest the primary effect is likely to be mainly attributable to
      diesel exhaust. Results for ischaemic heart disease below 65 years and for stroke
      over 65 years were inconclusive.

PMID- 12239205
TI  - Body mass index in young adulthood and cancer mortality: a retrospective cohort
      study.
AB  - STUDY OBJECTIVE: To examine the relation between body mass index (BMI) in young
      adulthood and subsequent mortality from cancer. DESIGN: Cohort study. SETTING:
      University of Glasgow student health service. Weight and height were measured by
      a physician, and used to calculate BMI. PARTICIPANTS: 8335 men and 2340 women who
      attended the student health service while at university between 1948 and 1968,
      and who were followed up with the NHS central register. MAIN RESULTS: The main
      outcome measure was cancer mortality. Three hundred and thirty nine men and 82
      women died of cancer during the follow up (mean 41 years). BMI was associated
      with mortality from all cancers in men and women, although it did not reach
      conventional statistical significance. The adjusted hazard ratio (HR) (95% CI)
      per 5 kg/m(2), was 1.22 (0.97 to 1.53) in men and 1.43 (0.95 to 2.16) in women.
      Two hundred men and 61 women died from cancers not related to smoking. The
      adjusted HR for mortality from these were 1.36 (1.02 to 1.82) and 1.80 (1.13 to
      2.86) respectively. These results are adjusted for height, number of siblings,
      pulse rate, year of birth, age, smoking, birth order, number of siblings, and age
      at menarche in women. Site specific analyses, comparing the highest with the
      lowest quartile of the BMI distribution found increased risks of prostate cancer
      (n=28) and breast cancer among heavier subjects. No association between BMI and
      colorectal cancer was found. CONCLUSIONS: BMI in adolescence has lasting
      implications for risk of cancer mortality in later life. Future research will
      include measures of BMI throughout the lifecourse, to determine the period of
      greatest risk of obesity, in terms of cancer mortality.

PMID- 12239206
TI  - Myocardial infarction in an urban population: worse long term prognosis for
      patients from less affluent residential areas.
AB  - STUDY OBJECTIVE: The objective in this follow up study from the Malmo myocardial
      infarction register has been to assess whether long term survival following
      discharge after first myocardial infarction has any relation with the
      socioeconomic environment and to assess to what extent intra-urban differences in
      mortality from ischaemic heart disease can be accounted for by covariance with
      long term survival following discharge after acute myocardial infarction. DESIGN:
      Register based surveillance study. SETTING: Seventeen residential areas in the
      city of Malmo, Sweden. PARTICIPANTS: The cohort contains all 2931 male and 2083
      female patients with myocardial infarction who were discharged for the first time
      between 1986-95 from Malmo University Hospital. MAIN RESULTS: During the on
      average 4.9 years of follow up 55% of the patients died. The sex adjusted and age
      adjusted all cause mortality rate/1000 patient years ranged between residential
      areas from 85.5 to 163.6. The area specific relative risk of death after
      discharge was associated with a low socioeconomic score, r=-0.56, p=0.018. Major
      risk factors for cardiovascular disease were more prevalent in areas with low
      socioeconomic score and low rates of survival. Of the intra-urban differences in
      mortality from ischaemic heart disease, 41% could be accounted for by differences
      with regard to the survival rate after discharge. CONCLUSIONS: The results are
      compatible with the hypothesis that the socioeconomic environment plays an
      important part in the survival rate of patients with myocardial infarction. To
      assess the preventive potential, the extent to which socioeconomic circumstances
      covary with severity of disease, respectively with the use and compliance with
      secondary preventive measures, needs to be evaluated.

PMID- 12239207
TI  - Gender differences in the management and outcome of patients with acute coronary
      artery disease.
AB  - STUDY OBJECTIVE: s: To compare the clinical management and health outcomes of men
      and women after admission with acute coronary syndromes, after adjusting for
      disease severity, sociodemographic, and cardiac risk factors. DESIGN: Prospective
      national survey of acute cardiac admissions followed up by mailed patient
      questionnaire two to three years after initial admission. SETTING: Random sample
      of 94 district general hospitals in the UK. PATIENTS: 1064 patients under 70
      years old recruited between April 1995 and November 1996. MAIN RESULTS: Of the
      1064 patients recruited, 126 (11.8%) died before follow up. Of the 938 survivors,
      719 (76.7%) completed a follow up questionnaire. There were no gender differences
      in the use of cardiac investigations during the index admission or follow up
      period. However, male patients with hypertension were more likely to undergo
      rehabilitation compared with female hypertensive patients (OR 2.01, 95% CI 0.85
      to 4.72). Men were also more likely to undergo coronary artery bypass grafting
      (CABG) than women (OR 1.90, 95%CI 1.21 to 3.00), but there was no gender
      difference in the use of revascularisation overall (p=0.14). An indirect
      indication that the gender differences in CABG were not attributable to bias was
      provided by the lack of gender differences in health outcomes, which implies that
      patients received the care they needed. CONCLUSIONS: Despite the extensive
      international literature referring to a gender bias in favour of men with
      coronary heart disease, this national survey found no gender differences in the
      use of investigations or in revascularisation overall. However, the criteria used
      for selecting percutaneous transluminal coronary angioplasty compared with CABG
      requires further investigation as does the use of rehabilitation. It is unclear
      whether the clinical decisions to provide these procedures are made solely on the
      basis of clinical need.

PMID- 12239208
TI  - Relation of occupational class and education with mortality in Korea.

PMID- 12239209
TI  - Calcineurin and NFAT4 induce chondrogenesis.
AB  - Nuclear factor of activated T-cells (NFAT) and calcineurin are essential
      regulators of immune cell and mesenchymal cell differentiation. Here we show that
      elevated intracellular calcium induces chondrogenesis through a calcineurin/NFAT
      signaling axis that activates bone morphogenetic protein (BMP) expression. The
      calcium ionophore, ionomycin, induced chondrogenesis through activation of
      calcineurin. The calcineurin substrate, NFAT4, also induced chondrogenesis and
      chondrocyte gene expression. Significantly, the BMP antagonist, noggin, or
      dominant negative BMP receptors blocked the effects of elevated intracellular
      calcium on chondrogenesis. This suggested that calcineurin/NFAT4 activates BMP
      expression. Consistent with this, BMP2 gene expression was increased by ionomycin
      and suppressed by the calcineurin inhibitor, cyclosporine A. Furthermore,
      activated NFAT4 induced BMP2 gene expression. These results have important
      implications for the effects of NFATs during development and adaptive responses.

PMID- 12239210
TI  - The two-step cleavage activity of PI-TfuI intein endonuclease demonstrated by
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry.
AB  - PI-TfuI, an intein spliced from the DNA polymerase of Thermococcus fumicolans, is
      a highly specific endonuclease, whose cleavage efficiency and specificity depend
      on both the substrate topology and the divalent cation used as cofactor. An open
      circular intermediate was observed during the cleavage of supercoiled DNA by PI
      TfuI, suggesting a two-step cleavage of the DNA. We characterized this nicked
      intermediate and, through the development of a method of analysis of the cleavage
      reaction based on matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry, we demonstrated that the cleavage of DNA by PI-TfuI indeed results
      from two cleavage events. One step results in the cleavage of the bottom strand,
      which is independent of the DNA conformation or choice of the metal ion cofactor.
      A second step, which is slower, leads to the cleavage of the top strand and
      governs the specific requirements of PI-TfuI concerning the essential cofactor
      and the DNA topology. These two steps were shown to be independent in optimal
      conditions of cleavage. These data give support to the existence of two distinct
      and independent active sites in the endonuclease domain of the archaeal intein.

PMID- 12239211
TI  - Misfolded proteins are competent to mediate a subset of the responses to heat
      shock in Saccharomyces cerevisiae.
AB  - Cells may sense heat shock via the accumulation of thermally misfolded proteins.
      To explore this possibility, we determined the effect of protein misfolding on
      gene expression in the absence of temperature changes. The imino acid analog
      azetidine-2-carboxylic acid (AZC) is incorporated into protein competitively with
      proline and causes reduced thermal stability or misfolding. We found that adding
      AZC to yeast at sublethal concentrations sufficient to arrest proliferation
      selectively induced expression of heat shock factor-regulated genes to a maximum
      of 27-fold and that these inductions were dependent on heat shock factor. AZC
      treatment also selectively repressed expression of the ribosomal protein genes,
      another heat shock factor-dependent process, to a maximum of 20-fold. AZC
      treatment thus strongly and selectively activates heat shock factor. AZC
      treatment causes this activation by misfolding proteins. Induction of HSP42 by
      AZC treatment required protein synthesis; treatment with ethanol, which can also
      misfold proteins, activated heat shock factor, but treatment with canavanine, an
      arginine analog less potent than AZC at misfolding proteins, did not. However,
      misfolded proteins did not strongly induce the stress response element regulon.
      We conclude that misfolded proteins are competent to specifically trigger
      activation of heat shock factor in response to heat shock.

PMID- 12239212
TI  - Inhibition of Wilms tumor 1 transactivation by bone marrow zinc finger 2, a novel
      transcriptional repressor.
AB  - The Wilms tumor suppressor gene, wt1, encodes a zinc finger transcription factor
      that has been implicated in the regulation of a number of genes. Protein-protein
      interactions are known to modulate the transcription regulatory functions of
      Wilms tumor (WT1) and have also implicated WT1 in splicing. In this report, we
      identify a novel WT1-interacting protein, bone marrow zinc finger 2 (BMZF2), by
      affinity chromatography utilizing immobilized WT1 protein. BMZF2 is a potential
      transcription factor with 18 zinc fingers. The BMZF2 mRNA is mainly expressed in
      fetal tissues, and the protein is predominantly nuclear. Co-immunoprecipitation
      experiments are consistent with an in vivo association between WT1 and BMZF2.
      Glutathione S-transferase pulldown assays and far Western blots revealed that
      zinc fingers VI-X (amino acids 231-370) are required for interaction with the
      zinc finger region of WT1. Functionally, BMZF2 inhibits transcriptional
      activation by WT1. Moreover, a chimeric protein generated by fusion of BMZF2 to
      the GAL4 DNA-binding domain significantly decreases promoter activity of a
      reporter containing GAL4 DNA-binding sites, suggesting the presence of an active
      repressor domain within BMZF2. Our results suggest that BMZF2 interferes with the
      transactivation potential of WT1.

PMID- 12239213
TI  - Tamapin, a venom peptide from the Indian red scorpion (Mesobuthus tamulus) that
      targets small conductance Ca2+-activated K+ channels and afterhyperpolarization
      currents in central neurons.
AB  - The biophysical properties of small conductance Ca(2+)-activated K(+) (SK)
      channels are well suited to underlie afterhyperpolarizations (AHPs) shaping the
      firing patterns of a conspicuous number of central and peripheral neurons. We
      have identified a new scorpion toxin (tamapin) that binds to SK channels with
      high affinity and inhibits SK channel-mediated currents in pyramidal neurons of
      the hippocampus as well as in cell lines expressing distinct SK channel subunits.
      This toxin distinguished between the SK channels underlying the apamin-sensitive
      I(AHP) and the Ca(2+)-activated K(+) channels mediating the slow I(AHP) (sI(AHP))
      in hippocampal neurons. Compared with related scorpion toxins, tamapin displayed
      a unique, remarkable selectivity for SK2 versus SK1 ( approximately 1750-fold)
      and SK3 ( approximately 70-fold) channels and is the most potent SK2 channel
      blocker characterized so far (IC(50) for SK2 channels = 24 pm). Tamapin will
      facilitate the characterization of the subunit composition of native SK channels
      and help determine their involvement in electrical and biochemical signaling.

PMID- 12239214
TI  - Transcriptional activity among high and low risk human papillomavirus E2 proteins
      correlates with E2 DNA binding.
AB  - The full-length E2 protein, encoded by human papillomaviruses (HPVs), is a
      sequence-specific transcription factor found in all HPVs, including cancer
      causing high risk HPV types 16 and 18 and wart-inducing low risk HPV types 6 and
      11. To investigate whether E2 proteins encoded by high risk HPVs may function
      differentially from E2 proteins encoded by low risk HPVs and animal
      papillomaviruses, we conducted comparative DNA-binding and transcription studies
      using electrophoretic mobility shift assays and cell-free transcription systems
      reconstituted with purified general transcription factors, cofactor, RNA
      polymerase II, and with E2 proteins encoded by HPV-16, HPV-18, HPV-11, and bovine
      papillomavirus type 1 (BPV-1). We found that although different types of E2
      proteins all exhibited transactivation and repression activities, depending on
      the sequence context of the E2-binding sites, HPV-16 E2 shows stronger
      transcription activity and greater DNA-binding affinity than those displayed by
      the other E2 proteins. Surprisingly, HPV-18 E2 behaves more similarly to BPV-1 E2
      than HPV-16 E2 in its functional properties. Our studies thus categorize HPV-18
      E2 and BPV-1 E2 in the same protein family, a finding consistent with the
      available E2 structural data that separate the closely related HPV-16 and HPV-18
      E2 proteins but classify together the more divergent BPV-1 and HPV-18 E2
      proteins.

PMID- 12239215
TI  - Activation of Rac1 and the p38 mitogen-activated protein kinase pathway in
      response to arsenic trioxide.
AB  - Arsenic trioxide induces differentiation and apoptosis of malignant cells in
      vitro and in vivo, but the mechanisms by which such effects occur have not been
      elucidated. In the present study we provide evidence that arsenic trioxide
      induces activation of the small G-protein Rac1 and the alpha and beta isoforms of
      the p38 mitogen-activated protein (MAP) kinase in several leukemia cell lines.
      Such activation of Rac1 and p38-isoforms results in downstream engagement of the
      MAP kinase-activated protein kinase-2 and is enhanced by pre-treatment of cells
      with ascorbic acid. Interestingly, pharmacological inhibition of p38 potentiates
      arsenic-dependent apoptosis and suppression of growth of leukemia cell lines,
      suggesting that this signaling cascade negatively regulates induction of
      antileukemic responses by arsenic trioxide. Consistent with this, overexpression
      of a dominant-negative p38 mutant (p38betaAGF) enhances the antiproliferative
      effects of arsenic trioxide on target cells. To further define the relevance of
      activation of the Rac1/p38 MAP kinase pathway in the induction of arsenic
      dependent antileukemic effects, studies were performed using bone marrows from
      patients with chronic myelogenous leukemia. Arsenic trioxide suppressed the
      growth of leukemic myeloid (CFU-GM) progenitors from such patients, whereas
      concomitant pharmacological inhibition of the p38 pathway enhanced its growth
      suppressive effects. Altogether, these data provide evidence for a novel function
      of the p38 MAP kinase pathway, acting as a negative regulator of arsenic trioxide
      induced apoptosis and inhibition of malignant cell growth.

PMID- 12239216
TI  - Saccharomyces cerevisiae RRM3, a 5' to 3' DNA helicase, physically interacts with
      proliferating cell nuclear antigen.
AB  - Proliferating cell nuclear antigen (PCNA) plays an essential role in eukaryotic
      DNA replication, and numerous DNA replication proteins have been found to
      interact with PCNA through a conserved eight-amino acid motif called the PIP-box.
      We have searched the genome of the yeast Saccharomyces cerevisiae for open
      reading frames that encode proteins with putative PIP-boxes and initiated testing
      of 135 novel candidates for their ability to interact with PCNA-conjugated
      agarose beads. The first new PCNA-binding protein identified in this manner is
      the 5' to 3' DNA helicase RRM3. Yeast two-hybrid tests show that N-terminal
      deletions of RRM3, which remove the PIP-box but leave the helicase motifs intact,
      abolish the interaction with PCNA. In addition, mutating the two phenylalanine
      residues in the PIP-box to alanine or aspartic acid reduces binding to PCNA,
      confirming that the PIP-box in RRM3 is responsible for interaction with PCNA. The
      results presented here suggest that the RRM3 helicase functions at the
      replication fork.

PMID- 12239217
TI  - Conserved residues in the putative catalytic triad of human bile acid Coenzyme
      A:amino acid N-acyltransferase.
AB  - Human bile acid-CoA:amino acid N-acyltransferase (hBAT), an enzyme catalyzing the
      conjugation of bile acids with the amino acids glycine or taurine has significant
      sequence homology with dienelactone hydrolases and other alpha/beta hydrolases.
      These enzymes have a conserved catalytic triad that maps onto the mammalian BATs
      at residues Cys-235, Asp-328, and His-362 of the human sequence, albeit that the
      hydrolases contain a serine instead of a cysteine. In the present study, the
      function of the putative catalytic triad of hBAT was examined by chemical
      modification with the cysteine alkylating reagent N-ethylmaleimide (NEM) and by
      site-directed mutagenesis of the triad residues followed by enzymology studies of
      mutant and wild-type hBATs. Treatment with NEM caused inactivation of wild-type
      hBAT. However, preincubation of wild-type hBAT with the substrate cholyl-CoA
      before NEM treatment prevented loss of N-acyltransferase activity. Substitution
      of His-362 or Asp-328 with alanine results in inactivation of hBAT. Although
      substitution of Cys-235 with serine generated an hBAT mutant with lower N
      acyltransferase activity, it substantially increased the bile acid-CoA
      thioesterase activity compared with wild type. In summary, data from this study
      support the existence of an essential catalytic triad within hBAT consisting of
      Cys-235, His-362, and Asp-328 with Cys-235 serving as the probable nucleophile
      and thus the site of covalent attachment of the bile acid molecule.

PMID- 12239218
TI  - Calnexin, calreticulin, and ERp57 cooperate in disulfide bond formation in human
      CD1d heavy chain.
AB  - Members of the CD1 family of membrane glycoproteins can present antigenic lipids
      to T lymphocytes. Like major histocompatibility complex class I molecules, they
      form a heterodimeric complex of a heavy chain and beta(2)-microglobulin
      (beta(2)m) in the endoplasmic reticulum (ER). Binding of lipid antigens, however,
      takes place in endosomal compartments, similar to class II molecules, and on the
      plasma membrane. Unlike major histocompatibility complex class I or CD1b
      molecules, which need beta(2)m to exit the ER, CD1d can be expressed on the cell
      surface as either a free heavy chain or associated with beta(2)m. These
      differences led us to investigate early events of CD1d biosynthesis and
      maturation and the role of ER chaperones in its assembly. Here we show that CD1d
      associates in the ER with both calnexin and calreticulin and with the thiol
      oxidoreductase ERp57 in a manner dependent on glucose trimming of its N-linked
      glycans. Complete disulfide bond formation in the CD1d heavy chain was
      substantially impaired if the chaperone interactions were blocked by the
      glucosidase inhibitors castanospermine or N-butyldeoxynojirimycin. The formation
      of at least one of the disulfide bonds in the CD1d heavy chain is coupled to its
      glucose trimming-dependent association with ERp57, calnexin, and calreticulin.

PMID- 12239219
TI  - Comparative mutagenesis of the C8-guanine adducts of 1-nitropyrene and 1,6- and
      1,8-dinitropyrene in a CpG repeat sequence. A slipped frameshift intermediate
      model for dinucleotide deletion.
AB  - In the Ames Salmonella typhimurium reversion assay 1,6- and 1,8-dinitropyrenes
      (1,6- and 1,8-DNPs) are much more potent mutagens than 1-nitropyrene (1-NP).
      Genetic experiments established that certain differences in the metabolism of the
      DNPs, which in turn result in increased DNA adduction, play a role. It remained
      unclear, however, if the DNP adducts, N-(guanin-8-yl)-1-amino-6 ()-nitropyrene
      (Gua-C8-1,6-ANP and Gua-C8-1,8-ANP), which contain a nitro group on the pyrene
      ring covalently linked to the guanine C8, are more mutagenic than the major 1-NP
      adduct, N-(guanin-8-yl)-1-aminopyrene (Gua-C8-AP). In order to address this, we
      have compared the mutation frequency of the three guanine C8 adducts, Gua-C8-AP,
      Gua-C8-1,6-ANP, and Gua-C8-1,8-ANP in a CGCG*CG sequence. Single-stranded
      M13mp7L2 vectors containing these adducts and a control were constructed and
      replicated in Escherichia coli. A remarkable difference in the induced CpG
      deletion frequency between these adducts was noted. In repair-competent cells the
      1-NP adduct induced 1.7% CpG deletions without SOS, whereas the 1,6- and 1,8-DNP
      adducts induced 6.8 and 10.0% two-base deletions, respectively. With SOS, CpG
      deletions increased up to 1.9, 11.1, and 15.1% by 1-NP, 1,6-, and 1,8-DNP
      adducts, respectively. This result unequivocally established that DNP adducts are
      more mutagenic than the 1-NP adduct in the repetitive CpG sequence. In each case
      the mutation frequency was significantly increased in a mutS strain, which is
      impaired in methyl-directed mismatch repair, and a dnaQ strain, which carries a
      defect in proofreading activity of the DNA polymerase III. Modeling studies
      showed that the nitro group on the pyrene ring at the 8-position can provide
      additional stabilization to the two-nucleotide extrahelical loop in the
      promutagenic slipped frameshift intermediate through its added hydrogen-bonding
      capability. This could account for the increase in CpG deletions in the M13
      vector with the nitro-containing adducts compared with the Gua-C8-AP adduct
      itself.

PMID- 12239220
TI  - Comparative surface accessibility of a pore-lining threonine residue (T6') in the
      glycine and GABA(A) receptors.
AB  - The substituted cysteine accessibility method was used to probe the surface
      exposure of a pore-lining threonine residue (T6') common to both the glycine
      receptor (GlyR) and gamma-aminobutyric acid, type A receptor (GABA(A)R) chloride
      channels. This residue lies close to the channel activation gate, the ionic
      selectivity filter, and the main pore blocker binding site. Despite their high
      amino acid sequence homologies and common role in conducting chloride ions,
      recent studies have suggested that the GlyRs and GABA(A)Rs have divergent open
      state pore structures at the 6' position. When both the human alpha1(T6'C)
      homomeric GlyR and the rat alpha1(T6'C)beta1(T6'C) heteromeric GABA(A)R were
      expressed in human embryonic kidney 293 cells, their 6' residue surface
      accessibilities differed significantly in the closed state. However, when a
      soluble cysteine-modifying compound was applied in the presence of saturating
      agonist concentrations, both receptors were locked into the open state. This
      action was not induced by oxidizing agents in either receptor. These results
      provide evidence for a conserved pore opening mechanism in anion-selective
      members of the ligand-gated ion channel family. The results also indicate that
      the GABA(A)R pore structure at the 6' level may vary between different expression
      systems.

PMID- 12239221
TI  - A CD36-initiated signaling cascade mediates inflammatory effects of beta-amyloid.
AB  - beta-Amyloid accumulation is associated with pathologic changes in the brain in
      Alzheimer's disease and has recently been identified in plaques of another
      chronic inflammatory disorder, atherosclerosis. The class B scavenger receptor,
      CD36, mediates binding of fibrillar beta-amyloid to cells of the
      monocyte/macrophage lineage, including brain macrophages (microglia). In this
      study, we demonstrate that in microglia and other tissue macrophages, beta
      amyloid initiates a CD36-dependent signaling cascade involving the Src kinase
      family members, Lyn and Fyn, and the mitogen-activated protein kinase, p44/42.
      Interruption of this signaling cascade, through targeted disruption of Src
      kinases downstream of CD36, inhibits macrophage inflammatory responses to beta
      amyloid, including reactive oxygen and chemokine production, and results in
      decreased recruitment of microglia to sites of amyloid deposition in vivo. The
      finding that engagement of CD36 by beta-amyloid initiates a Src kinase-dependent
      production of inflammatory mediators in cells of the macrophage lineage reveals a
      novel receptor-mediated pro-inflammatory signaling pathway of potential
      therapeutic importance.

PMID- 12239222
TI  - AQP3 deficiency in humans and the molecular basis of a novel blood group system,
      GIL.
AB  - AQP3 is a water and glycerol channel present on human erythrocytes and in various
      tissues. By protein and molecular biology analysis, two unrelated probands who
      developed alloantibodies to the high frequency antigen GIL were found to be AQP3
      deficient. The defect is caused by homozygous mutation affecting the 5' donor
      splice site of intron 5 of the AQP3 gene. This mutation causes the skipping of
      exon 5 and generates a frameshift and premature stop codon. Functional studies by
      90 degrees light scattering using a stopped-flow spectrometer revealed the
      absence of facilitated glycerol transport across red cell membranes from the
      probands, but the water and urea transports were normal. Expression studies into
      COS-7 cells followed by flow cytometry analysis showed that only cells
      transfected with AQP3 cDNA strongly reacted with anti-GIL antibodies. These
      findings represent the first reported cases of AQP3 deficiency in humans and
      provide the molecular basis of a new blood group system, GIL, encoded by the AQP3
      protein.

PMID- 12239223
TI  - Gastrin stimulates cyclooxygenase-2 expression in intestinal epithelial cells
      through multiple signaling pathways. Evidence for involvement of ERK5 kinase and
      transactivation of the epidermal growth factor receptor.
AB  - Gastrin is a hormone produced by G-cells in the normal gastric antrum. However,
      colorectal carcinoma cells may aberrantly produce gastrin and exhibit increased
      expression of cholecystokinin B (CCK-B)/gastrin receptors. Gastrin is trophic for
      the normal gastric oxyntic mucosa and exerts a growth-promoting action on
      gastrointestinal malignancy. Thus, gastrin may act as an autocrine/paracrine or
      endocrine factor in the initiation and progression of colorectal carcinoma. The
      molecular mechanisms involved have not been elucidated. Hypergastrinemia induced
      by Helicobacter pylori infection is associated with increased cyclooxygenase-2
      (COX-2) expression in gastric and colorectal tissues, suggesting the possibility
      that gastrin up-regulates COX-2 expression in these tissues; this has not been
      confirmed. We report here that gastrin significantly increases the expression of
      COX-2 mRNA and protein, the activity of the COX-2 promoter, and the release of
      prostaglandin E(2) from a rat intestinal epithelial cell line transfected with
      the CCK-B receptor. These actions were dependent upon the activation of multiple
      MAPK signal pathways, including ERK5 kinase; transactivation of the epidermal
      growth factor receptor; and the increased expression and activities of
      transcription factors ELK-1, activating transcription factor-2, c-Fos, c-Jun,
      activator protein-1, and myocyte enhancer factor-2. Thus, our findings identify
      the signaling pathways coupling the CCK-B receptor with up-regulation of COX-2
      expression. This effect may contribute to this hormone-dependent gastrointestinal
      carcinogenesis, especially in the colon.

PMID- 12239224
TI  - The need for antimicrobial resistance surveillance.
AB  - Although antimicrobial agents drastically reduced patient morbidity and
      mortality, bacterial resistance to these agents developed shortly after their
      introduction. Because the laboratory diagnosis of respiratory tract infection
      (RTI) is not always possible, and rarely of immediate use, treatment success or
      failure often depends upon the availability of reliable susceptibility
      information at the time of therapeutic decision-making. Hence, the need for
      accurate, up-to-date and timely data is obvious. This information can also be
      used to help determine the cause of antimicrobial resistance and how it spreads.
      Desired components of a global RTI surveillance study fall into four categories:
      programme design, methodology, clinical and dissemination of information. PROTEKT
      (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide
      Telithromycin) is an RTI surveillance study designed to fulfil these
      requirements. PROTEKT includes all of the features of other successful RTI
      surveillance studies (e.g. the Alexander Project, SENTRY) and improves on these
      studies by the addition of other desirable features, such as the determination of
      resistance mechanisms and the availability of up-to-date local data that can be
      downloaded to hand-held computers via the worldwide web for use at the bedside.

PMID- 12239225
TI  - Antimicrobial resistance amongst isolates of Streptococcus pyogenes and
      Staphylococcus aureus in the PROTEKT antimicrobial surveillance programme during
      1999-2000.
AB  - The pattern of susceptibility to a range of antimicrobials was tested for 1485
      isolates of Streptococcus pyogenes and 1547 isolates of Staphylococcus aureus
      included in the international PROTEKT (Prospective Resistant Organism Tracking
      and Epidemiology for the Ketolide Telithromycin) surveillance study (1999-2000).
      Overall, almost 10% of S. pyogenes isolates were erythromycin A resistant. There
      was a wide heterogeneity of resistance, with high levels of macrolide resistance
      in Poland (42%), Hong Kong (28%), Italy (25%), Portugal (24%) and Spain (21%),
      and no macrolide resistance in Indonesia, Austria, Belgium, the Netherlands or
      the UK. Using NCCLS tentative breakpoints, 97.6% of isolates were susceptible to
      telithromycin, with MIC(90) < or = 0.015 mg/L in most regions. Resistance among
      S. pyogenes to the beta-lactams (MIC(90) < or = 0.12 mg/L for all except
      cefaclor) and fluoroquinolones was not detected. Macrolide resistance was present
      among the S. aureus isolates, and as with S. pyogenes, there was a wide
      heterogeneity of resistance, with lower rates in Australia, Indonesia, Hungary,
      Austria, Germany, the Netherlands, Portugal, Sweden and Switzerland. Methicillin
      resistant isolates were resistant to the beta-lactams and the macrolides.
      Resistance to telithromycin was detected in methicillin-resistant isolates in
      Latin and North America, Asia and Europe. Telithromycin resistance was non
      existent or low (MIC(90 )range 0.06-0.25 mg/L) in Australia, Indonesia, Hungary,
      Austria, Germany, the Netherlands, Portugal, Sweden and Switzerland. Regardless
      of methicillin susceptibility, resistance to linezolid, teicoplanin or vancomycin
      was not apparent globally.

PMID- 12239226
TI  - Increasing prevalence of antimicrobial resistance among isolates of Streptococcus
      pneumoniae from the PROTEKT surveillance study, and compatative in vitro activity
      of the ketolide, telithromycin.
AB  - The prevalence of resistance to a range of antimicrobials was determined for
      isolates of Streptococcus pneumoniae examined in the PROTEKT (Prospective
      Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin)
      surveillance study (1999-2000) using NCCLS testing methods and interpretative
      criteria. Of 3362 pneumococcal isolates collected from 69 centres in 25
      countries, 22.1% overall were resistant to penicillin G, with the highest rates
      of resistance found among isolates from Asia (53.4%), France (46.2%) and Spain
      (42.1%). Erythromycin A resistance occurred in 31.1% of isolates overall with the
      highest rates found in Asia (79.6%), France (57.6%), Hungary (55.6%) and Italy
      (42.9%). Marked geographical differences in the prevalence of both penicillin G
      (the Netherlands 0%; South Korea 71.5%) and erythromycin A (Sweden 4.7%; South
      Korea 87.6%) resistance were observed. Asia was characterized by the highest
      prevalence of resistance, overall, with only eight of 19 antimicrobials (co
      amoxiclav, linezolid, vancomycin, teicoplanin, quinupristin/dalfopristin,
      levofloxacin, moxifloxacin and telithromycin) retaining high activity against
      isolates of S. pneumoniae from this region. Notable rates of resistance to
      clarithromycin, azithromycin, co-trimoxazole and tetracycline were observed in
      the majority of countries submitting isolates of S. pneumoniae to the PROTEKT
      surveillance study. Fluoroquinolone resistance was low (1%), overall, although
      14.3% of 70 isolates from Hong Kong were resistant to levofloxacin and
      moxifloxacin, all but one of these isolates belonging to a single clone of the
      23F serotype. Although, at present, apparently limited to pockets of clonal
      spread, continued vigilance with regard to the evolution of fluoroquinolone
      resistance is indicated. Telithromycin (MIC(90) 0.12 mg/L; 99.9% of isolates
      susceptible) and lin- ezolid (MIC(90) 2 mg/L; 100% of isolates susceptible) were
      the two most active oral agents tested, both compounds retaining activity against
      isolates of fluoroquinolone-resistant S. pneumoniae. The results of the PROTEKT
      surveillance study 1999-2000 emphasize the widespread evolution of resistance to
      a variety of antimicrobials amongst isolates of S. pneumoniae and demonstrate the
      potential of telithromycin as a therapeutic option for the treatment of community
      acquired respiratory tract infections caused by this organism.

PMID- 12239227
TI  - Molecular characterization of macrolide resistance mechanisms among Streptococcus
      pneumoniae and Streptococcus pyogenes isolated from the PROTEKT 1999-2000 study.
AB  - In this study, the distribution of macrolide resistance mechanisms was determined
      for isolates of Streptococcus pneumoniae and Streptococcus pyogenes obtained from
      the PROTEKT 1999-2000 study (a global, longitudinal study of the antibacterial
      susceptibility of bacterial pathogens associated with community-acquired lower
      respiratory tract infections). The global macrolide resistance mechanism
      distribution results for 1043 macrolide-resistant S. pneumoniae isolates
      collected from 25 countries were as follows: 35.3% mef(A), 56.2% erm(B), 6.8%
      both mef(A) and erm(B), 0.2% erm(A) subclass erm(TR) and 1.5% negative for
      mechanisms tested. Mechanisms of macrolide resistance were found to vary widely
      between countries and different geographical regions with mef(A) predominating in
      North America and erm(B) in Europe. Approximation of genotype from macrolide MIC
      without molecular determination of the mechanism of resistance resulted in an
      error of 10.2% (106 isolates). Overall, for 143 macrolide-resistant S. pyogenes
      isolates, 46.1% of the isolates tested were mef(A), 30.8% were erm(B), 23.1% were
      erm(A) subclass erm(TR) and no isolates were negative for all the genetic markers
      tested. Again, the distribution varied widely between countries and geographical
      regions. This study provides valuable baseline data for the continued monitoring
      of the evolution of macrolide resistance development in these important
      respiratory tract pathogens. The ketolide telithromycin retained excellent anti
      pneumococcal activity irrespective of macrolide resistance mechanism, having a
      MIC(90) of 0.25, 0.5 and 0.5 mg/L against mef(A), erm(B) and mef(A)+erm(B)
      macrolide-resistant S. pneumoniae, respectively. It also exhibited potent
      activity against S. pyogenes that had become resistant to macrolides via either
      mef(A), (MIC(90 )0.5 mg/L) or erm(TR), (MIC(90) 0.03 mg/L).

PMID- 12239228
TI  - The PROTEKT surveillance study: antimicrobial susceptibility of Haemophilus
      influenzae and Moraxella catarrhalis from community-acquired respiratory tract
      infections.
AB  - This paper presents data relating to Haemophilus influenzae and Moraxella
      catarrhalis from PROTEKT (1999-2000), a surveillance study that examined the
      susceptibility of respiratory pathogens to current and new antibacterials. Beta
      lactamase production is the principal mechanism of resistance to ampicillin and
      other beta-lactam antibacterials in H. influenzae and M. catarrhalis. The PROTEKT
      study showed that globally, the prevalence of beta-lactamase production in H.
      influenzae varied considerably: of 2948 isolates, 489 (16.6%) were beta-lactamase
      positive [range: 1.8% (Italy) to 65% (South Korea)]. Beta-lactamase-negative,
      ampicillin-resistant (BLNAR) strains of H. influenzae were uncommon (<0.1%) but
      their very detection highlights the need for continued vigilance. Overall, few
      isolates of H. influenzae showed resistance to either macrolides or
      telithromycin. The emergence of clarithromycin-resistant strains is worrying,
      however, as such isolates may also show resistance to other macrolides. There was
      a geographical correlation between beta-lactamase production and the prevalence
      of resistance to chloramphenicol and tetracycline among the H. influenzae
      isolates. Of 1131 M. catarrhalis isolates, 92% were beta-lactamase-positive. Most
      isolates, however, were fully susceptible to nearly all the antibacterials
      tested, except ampicillin. The most active were ciprofloxacin and levofloxacin
      (both having MIC(90) values of 0.03 mg/L), moxifloxacin (MIC(90) 0.06 mg/L),
      azithromycin (MIC(90) < or = 0.06 mg/L) and telithromycin (MIC(90) 0.12 mg/L).
      Overall, there were no concerns in terms of resistance to fluoroquinolones for
      both H. influenzae and M. catarrhalis. In summary, the PROTEKT surveillance study
      confirmed the problem of widespread prevalence of beta-lactamase-producing
      strains of H. influenzae and M. catarrhalis, although these pathogens generally
      remain susceptible to macrolides, fluoroquinolones and the new ketolide
      telithromycin.

PMID- 12239229
TI  - Clinical and economic implications of antimicrobial resistance for the management
      of community-acquired respiratory tract infections.
AB  - Lower respiratory tract infections (RTIs), particularly community-acquired
      pneumonia (CAP), account for over 50 million deaths annually worldwide. They
      place an extensive clinical and financial burden on healthcare authorities. Upper
      RTIs, usually mild and non-life threatening, also incur significant healthcare
      costs. The rising prevalence of resistance of the major causative agents of CAP
      (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) to
      beta-lactam antimicrobials and newer macrolides has necessitated new strategies
      for appropriate antimicrobial usage. A successful clinical outcome will depend on
      the patient, choice of drug, and the epidemiology and resistance of the pathogen.
      Treatment failure will result in increased costs, particularly if hospitalization
      is required. Pharmacokinetic and pharmacodynamic parameters are being used
      increasingly to predict maximally effective therapy and optimal bacterial
      eradication, thus limiting the development of resistance. Antimicrobial
      susceptibility criteria by MIC should be dictated by the type and location of the
      infection. Modifying the current MIC breakpoints for penicillin so that more
      pneumococcal pneumonia isolates are reported appropriately as being susceptible
      may lead to a decrease in the use of broad-spectrum antimicrobial therapy and its
      associated increased costs, in favour of more narrow-spectrum therapy. Targeting
      the pathogen with the most effective antimicrobial in an appropriately selected
      patient should optimize clinical and microbiological success and, consequently,
      maximize response rates and economic outcomes. In addition, research efforts need
      to concentrate on developing new agents with low propensity to select for or
      induce resistance.

PMID- 12239231
TI  - Cyclosporine A suppresses cyclooxygenase-2 expression in the rat kidney.
AB  - On the basis of recent evidence that the cyclooxygenase-2 (COX-2) gene promoter
      contains functional binding sites for the nuclear factor of activated T cells
      (NFAT) and that COX-2 is expressed in a regulated fashion in the kidney, this
      study aimed to assess the effect of immunosuppressants on COX-2 expression in the
      kidney. Therefore, Wistar-Kyoto rats were treated with cyclosporine A (CsA; 15
      mg/kg per day) or tacrolimus (5 mg/kg per day) for 7 d each. Both drugs markedly
      lowered COX-2 expression while COX-1 expression remained unaltered. Furthermore,
      CsA blunted the increase of renocortical COX-2 expression in response to low salt
      intake or a combination of low-salt diet with the ACE inhibitor ramipril (10
      mg/kg per day), which strongly stimulates renocortical COX-2 expression. At the
      same time, calcineurin inhibitors moderately enhanced basal as well as stimulated
      renin secretion and renin gene expression. These findings suggest that inhibition
      of calcineurin could be a crucial determinant for the regulated expression of COX
      2 in the kidney. Inhibition of COX-2 expression may therefore at least in part
      account for the well-known adverse effects of immunosuppressants in the kidney.
      Moreover, our data suggest that the stimulation of the renin system by low salt
      and by ACE inhibitors is not essentially mediated by COX-2 activity.

PMID- 12239232
TI  - Connective tissue growth factor and regulation of the mesangial cell cycle: role
      in cellular hypertrophy.
AB  - Connective tissue growth factor (CTGF) is now considered to be one of the
      important driver molecules for the pathogenesis of diabetic nephropathy (DN) and
      possibly many other fibrotic disorders. However, the molecular mechanisms by
      which CTGF functions remain to be established. In an attempt to define these
      mechanisms, this study was designed to investigate whether CTGF has any effect on
      the cell cycle of human mesangial cells (HMC), which are known to undergo
      hypertrophy in DN. This report provides the first evidence that CTGF is a
      hypertrophic factor for HMC. CTGF stimulates HMC to actively enter the G(1) phase
      from G(0), but they do not then progress further through the cell cycle. The
      molecular mechanisms underlying this G(1) phase arrest appear to be due to the
      induction of the cyclin-dependent kinase inhibitors (CDKI) p15(INK4), p21(Cip1),
      and p27(Kip1), which are known to bind and inactivate cyclinD/CDK4/6 and the
      cyclin E/CDK2 kinase complexes. This could account for the maintenance of pRb
      protein in a non- or very low-phosphorylated state, preventing cell cycle
      progression. Using CTGF antisense oligonucleotides, the results also indicate
      that the previously identified transforming growth factor-beta (TGF-beta)-induced
      hypertrophy in mesangial cells is CTGF-dependent. Mesangial cell hypertrophy is
      one of the earliest abnormalities of diabetic nephropathy; therefore, therapeutic
      strategies targeting CTGF may be beneficial in controlling DN.

PMID- 12239233
TI  - SBA-positive fibers between the CD ampulla, mesenchyme, and renal capsule.
AB  - During kidney development, the CD shows two peculiarities. First, the tip of the
      CD ampulla is always found at a specific distance from the organ capsule. Second,
      the CD growth occurs as a perfectly straight elongation. It is unknown whether
      the CD-specific growth is dependent on hormonal action or on structural elements.
      Histochemical experiments on neonatal rabbit kidney yielded new insight into the
      interface of the CD ampulla and the surrounding nephrogenic mesenchyme.
      Incubation of tissue sections with soybean lectin (SBA) showed the existence of
      fibers extending in a radial course from the ampullar tip through the mesenchyme
      toward the organ capsule. SBA labeling did not colocalize with collagen type I,
      III, IV, V, and VI, laminin, fibronectin, and tenascin. It is assumed that while
      the kidney increases in volume the structural fixation of the ampullar tip by the
      SBA-positive fibers causes CD ampullae to maintain a constant distance from the
      organ capsule. The connection would explain the linear extension of the CD in
      relation to the organ capsule. In addition, the presented data suggest that the
      SBA-positive fibers between ampullar tip and organ capsule create a structural
      microcompartmentation of the nephrogenic zone.

PMID- 12239234
TI  - Physiologic consequences of vasopeptidase inhibition in humans: effect of sodium
      intake.
AB  - The in vivo inhibition of angiotensin-converting enzyme (ACE) and neutral
      endopeptidase (NEP) were monitored simultaneously by sequentially measuring the
      urinary excretion of N-Acetyl-Ser-Asp-Lys-Pro and of the atrial natriuretic
      factor to compare the magnitude and the duration of action of a vasopeptidase
      inhibitor, omapatrilat, and an ACE inhibitor, fosinopril. Single oral doses of 40
      or 80 mg of omapatrilat or 20 mg of fosinopril were administered to 24
      normotensive, sodium-depleted or -replete volunteers in a placebo-controlled
      crossover study. ACE inhibition persisted longer after treatment with omapatrilat
      than with fosinopril, and there was no major difference between the effects of 40
      and 80 mg of omapatrilat. The duration of NEP inhibition by omapatrilat was
      shorter than that of ACE inhibition. Although omapatrilat effectively inhibited
      NEP, it had a mild and transient natriuretic effect and did not increase
      natriuresis more than fosinopril. Omapatrilat induced a decrease in BP and an
      increase in plasma renin more rapidly and more effectively than fosinopril. The
      BP and renin effects of omapatrilat persisted despite high sodium intake, which
      neutralized the effects of fosinopril. The simultaneous inhibition of ACE and NEP
      may be more effective in reducing BP than the inhibition of ACE alone and less
      dependent on sodium balance.

PMID- 12239235
TI  - Hepatocyte growth factor gene therapy and angiotensin II blockade synergistically
      attenuate renal interstitial fibrosis in mice.
AB  - Tubulointerstitial fibrosis is considered to be common endpoint result of many
      forms of chronic renal diseases. Except for renal replacement, chronic renal
      fibrosis is presently incurable. This study demonstrates that the combination of
      hepatocyte growth factor (HGF) gene therapy with inhibition of the renin
      angiotensin system produced synergistic beneficial effects leading to dramatic
      attenuation of renal tubulointerstitial fibrosis in obstructive nephropathy in
      mice. The combined treatment with human HGF gene and losartan, an angiotensin II
      (AngII) type I receptor blocker, preserved renal mass and gross morphology of the
      obstructed kidneys. Although HGF gene therapy alone inhibited the expression of
      alpha-smooth muscle actin (alpha SMA) by approximately 54% and 60% at day 7 and
      day 14 after surgery, respectively, its combination with losartan almost
      completely abolished alpha SMA induction in the obstructed kidneys. The combined
      therapy also synergistically inhibited the accumulation of interstitial matrix
      components, such as fibronectin and collagen I, and suppressed renal expression
      of transforming growth factor-beta1 (TGF-beta1) and its type I receptor. In vitro
      studies revealed that AngII by itself did not induce alpha SMA, but it
      drastically potentiated TGF-beta1-initiated alpha SMA expression in tubular
      epithelial cells. Furthermore, HGF abrogated de novo alpha SMA expression induced
      by TGF-beta1 plus AngII. These results suggest that many factors are implicated
      in the pathogenesis of renal interstitial fibrosis; therefore, a combined therapy
      aimed at simultaneously targeting multiple pathologic pathways may be necessary
      for halting the progression of chronic renal diseases. These findings may provide
      the basis for designing future therapeutic regimens for blocking progressive
      renal fibrosis in patients.

PMID- 12239236
TI  - Angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors
      lower in vitro the formation of advanced glycation end products: biochemical
      mechanisms.
AB  - The implication of advanced glycation end products (AGE) in the pathogenesis of
      atherosclerosis and of diabetic and uremic complications has stimulated a search
      for AGE inhibitors. This study evaluates the AGE inhibitory potential of several
      well-tolerated hypotensive drugs. Olmesartan, an angiotensin II type 1 receptor
      (AIIR) antagonist, as well as temocaprilat, an angiotensin-converting enzyme
      (ACE) inhibitor, unlike nifedipine, a calcium blocker, inhibit in vitro the
      formation of two AGE, pentosidine and N(epsilon)-carboxymethyllysine (CML),
      during incubation of nonuremic diabetic, nondiabetic uremic, or diabetic uremic
      plasma or of BSA fortified with arabinose. This effect is shared by all tested
      AIIR antagonists and ACE inhibitors. On an equimolar basis, they are more
      efficient than aminoguanidine or pyridoxamine. Unlike the latter two compounds,
      they do not trap reactive carbonyl precursors for AGE, but impact on the
      production of reactive carbonyl precursors for AGE by chelating transition metals
      and inhibiting various oxidative steps, including carbon-centered and hydroxyl
      radicals, at both the pre- and post-Amadori steps. Their effect is paralleled by
      a lowered production of reactive carbonyl precursors. Finally, they do not bind
      pyridoxal, unlike aminoguanidine. Altogether, this study demonstrates for the
      first time that widely used hypotensive agents, AIIR antagonists and ACE
      inhibitors, significantly attenuate AGE production. This study provides a new
      framework for the assessment of families of AGE-lowering compounds according to
      their mechanisms of action.

PMID- 12239237
TI  - Human platelets stimulate mesangial cells to produce monocyte chemoattractant
      protein-1 via the CD40/CD40 ligand pathway and may amplify glomerular injury.
AB  - Platelets are thought to play an important role in the initiation and the
      progression of a variety of glomerulonephritides. This study examined whether
      platelets induce production of monocyte chemoattractant protein-1 (MCP-1), a
      chemokine involved in leukocyte recruitment and glomerular injury, by cultured
      human mesangial cells (MC). To this end, platelets isolated from normal human
      donors were cocultured with MC at various ratios. MCP-1 synthesis was evaluated
      by quantitative real-time PCR and enzyme-linked immunosorbent assay. Platelets at
      1:100 ratio (MC to platelets) induced an approximately 20-fold increase in
      mesangial MCP-1 mRNA and protein expression through an obligatory cell-to-cell
      contact-dependent mechanism. Importantly, blockade of the CD40/CD40 ligand
      (CD40L) pathway with neutralizing antibodies decreased MCP-1 production by
      approximately 60%. It was confirmed that CD40 was functionally expressed on MC.
      Gel-shift assays and inhibitors of phosphorylation were used to demonstrate that
      activation of p38 mitogen-activated protein kinase, protein tyrosine kinases, and
      nuclear factor-kappa B activation were essential for MCP-1 production. These data
      indicate that platelet/MC contact stimulates the production of MCP-1 and may
      contribute to glomerular inflammatory responses by recruiting leukocytes from the
      peripheral blood.

PMID- 12239238
TI  - Lipoxins, aspirin-triggered epi-lipoxins, lipoxin stable analogues, and the
      resolution of inflammation: stimulation of macrophage phagocytosis of apoptotic
      neutrophils in vivo.
AB  - Lipoxins (LX) are eicosanoids with antiinflammatory activity in
      glomerulonephritis (GN) and inflammatory diseases, hypersensitivity, and ischemia
      reperfusion injury. It has been demonstrated that LXA(4) stimulates non
      phlogistic phagocytosis of apoptotic polymorphonuclear neutrophils (PMN) by
      monocyte-derived macrophages (Mphi) in vitro, suggesting a role for LX as
      endogenous pro-resolution lipid mediators. It is here reported that LXA(4),
      LXB(4), the aspirin-triggered LX (ATL) epimer, 15-epi-LXB(4), and a stable
      synthetic analogue 15(R/S)-methyl-LXA(4) stimulate phagocytosis of exogenously
      administered excess apoptotic PMN by macrophages (M phi) in vivo in a classic
      model of acute inflammation, namely thioglycollate-induced peritonitis.
      Significant enhancement of phagocytosis in vivo was observed with 15-min exposure
      to LX and with intraperitoneal doses of LXA(4), LXB(4), 15(R/S)-methyl-LXA(4),
      and 15-epi-LXB(4) of 2.5 to 10 micro g/kg. Non-phlogistic LX-stimulated
      phagocytosis by M phi was sensitive to inhibition of PKC and PI 3-kinase and
      associated with increased production of transforming growth factor-beta(1) (TGF
      beta(1)). LX-stimulated phagocytosis was not inhibited by phosphatidylserine
      receptor (PSR) antisera and was abolished by prior exposure of M phi to beta 1,3
      glucan, suggesting a novel M phi-PMN recognition mechanism. Interestingly, the
      recently described peptide agonists of the LXA(4) receptor (MYFINITL and
      LESIFRSLLFRVM) stimulated phagocytosis through a process associated with
      increased TGF-beta(1) release. These data provide the first demonstration that
      LXA(4), LXB(4), ATL, and LX stable analogues rapidly promote M phi phagocytosis
      of PMN in vivo and support a role for LX as rapidly acting, pro-resolution
      signals in inflammation. Engagement of the LXR by LX generated during cell-cell
      interactions in inflammation and by endogenous LXR peptide agonists released from
      distressed cells may be an important stimulus for clearance of apoptotic cells
      and may be amenable to pharmacologic mimicry for therapeutic gain.

PMID- 12239239
TI  - The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and
      cystin, are co-localized in renal cilia.
AB  - Recent evidence has suggested an association between structural and/or functional
      defects in the primary apical cilium of vertebrate epithelia and polycystic
      kidney disease (PKD). In Caenorhabditis elegans, the protein orthologues of the
      PKD-related proteins, polycystin-1 (LOV-1), polycystin-2 (PKD2), and polaris (OSM
      5), co-localize in the cilia of male-specific sensory neurons, and defects in
      these proteins cause abnormalities of cilia structure and/or function. This study
      sought to determine whether the mammalian polycystins are expressed in primary
      cilia of renal epithelia and whether these proteins co-localize with polaris and
      cystin, the newly described, cilia-associated protein that is disrupted in the
      cpk mouse. To begin to address this issue, the expression of the protein products
      encoded by the PKD1, PKD2, Tg737, and cpk genes were examined in mouse cortical
      collecting duct (mCCD) cells using an immunofluorescence-based approach with a
      series of previously well-characterized antibodies. The mCCD cells were grown on
      cell culture inserts to optimize cell polarization and cilia formation. The data
      demonstrate co-localization in cilia of polycystin-1 and polycystin-2, which are
      the principal proteins involved in autosomal dominant polycystic kidney disease,
      with polaris and cystin, which are proteins that are disrupted in the
      Tg737(orpk)and cpk mouse models of autosomal recessive polycystic kidney disease,
      respectively. These data add to a growing body of evidence that suggests that
      primary cilium plays a key role in normal physiologic functions of renal
      epithelia and that defects in ciliary function contribute to the pathogenesis of
      PKD.

PMID- 12239240
TI  - Influence of calcium-sensing receptor gene on urinary calcium excretion in stone
      forming patients.
AB  - Calcium-sensing receptor (CaSR) is a plasma membrane protein that regulates
      tubular reabsorption of Ca. To establish its role in idiopathic hypercalciuria,
      the association of urinary Ca excretion with the polymorphisms of CASR gene has
      been studied in healthy subjects and in hypercalciuric and normocalciuric Ca
      stone formers. CASR exon 7 single nucleotide polymorphisms (SNP), G/T at codon
      986, G/A at codon 990, and C/G at codon 1011, were evaluated by PCR amplification
      and direct sequencing in 97 normocalciuric stone formers, 134 hypercalciuric
      stone formers, and 101 normocalciuric healthy controls. Four haplotypes were
      defined on the basis of CASR gene SNP: haplotype 1 was characterized by the most
      frequent sequence; haplotypes 2, 3, or 4 by the presence of a single polymorphic
      variant at codon 986, 990, or 1011, respectively. The relative risk of
      hypercalciuria was calculated with multinomial logistic regression and was
      significantly increased only in individuals carrying haplotype 3 (Odds ratio,
      13.0 [95% confidence interval, 1.7 to 99.4]). Accordingly, Ca excretion was
      higher in subjects bearing haplotype 3, whereas those bearing haplotype 2 showed
      a slight increase of plasma Ca concentration. Multiple regression analysis showed
      that haplotype 3 explained 4.1% of the total variance of Ca excretion and 12.6%
      of the variance explained by the variables considered in the study. In
      conclusion, CASR gene could be a component of the complex genetic background
      regulating Ca excretion. Arg990Gly polymorphism could facilitate activation of
      CaSR and increase Ca excretion and susceptibility to idiopathic hypercalciuria.

PMID- 12239241
TI  - Mycophenolate mofetil attenuates renal ischemia/reperfusion injury.
AB  - Immunosuppressive agents may have an impact on ischemia/reperfusion (I/R) injury.
      The immunosuppressant mycophenolate mofetil (MMF) presents properties that can
      attenuate such injury. This study investigated the effects of MMF on renal I/R
      injury. Male Wistar rats received MMF (20 mg/kg per d) or vehicle by gavage
      beginning 2 d before ischemia and maintained during the entire study. Ischemic
      injury was induced by bilateral renal arteries occlusion for 60 min. Control rats
      received MMF and underwent sham operation. At days 1, 2, and 14, post-ischemia
      renal function was assessed and kidneys were removed for histologic and
      immunohistochemical studies. MMF given to nonischemic rats did not alter renal
      function. There was no functional protection at 24 h post-ischemia with MMF. At 2
      d, post-ischemia rats pretreated with MMF presented higher inulin clearance
      compared with untreated rats (0.42 +/- 0.04 versus 0.15 +/- 0.02 ml/min per 100
      g; P < 0.001) and attenuated renal blood flow decrease (5.23 +/- 0.28 versus 3.24
      +/- 0.37 ml/min; P < 0.01). The immunostaining for intercellular adhesion
      molecule-1 (ICAM-1) was less intense in rats pretreated with MMF. These rats also
      presented an earlier decreased infiltrating macrophages/lymphocytes and cell
      proliferation at day 1 post-ischemia. The functional and immunohistochemical
      analyses performed at day 14 post-ischemia returned to values similar to controls
      in both groups of rats. To determine whether mycophenolic acid (MPA) could induce
      cytoprotection, the effects of MPA on normoxic and hypoxic/reoxygenated (H/R)
      isolated tubule suspensions were also investigated. MPA was not deleterious to
      normoxic tubules and it was not protective against H/R tubules. In conclusion,
      pretreatment with MMF attenuates I/R injury in rats and does not limit the
      recovery from ischemia. The protective effect of MMF by reducing inflammation
      precedes the hemodynamic changes and tubular injury.

PMID- 12239242
TI  - Cortisol inhibits acid-induced bone resorption in vitro.
AB  - Metabolic acidosis increases urine calcium excretion without an increase in
      intestinal calcium absorption, resulting in a net loss of bone mineral. In vitro,
      metabolic acidosis has been shown to initially induce physicochemical mineral
      dissolution and then enhance cell-mediated bone resorption. Acidic medium
      stimulates osteoblastic prostaglandin E(2) production, which mediates the
      subsequent stimulation of osteoclastic bone resorption. Glucocorticoids are also
      known to decrease bone mineral density, and metabolic acidosis has been shown to
      increase glucocorticoid production. This study tested the hypothesis that
      glucocorticoids would exacerbate acid-induced net calcium efflux from bone.
      Neonatal mouse calvariae were cultured in acid (Acid; pH = 7.06 +/- 0.01;
      [HCO(3)(-)] = 10.6 +/- 0.3 mM) or neutral (Ntl; pH = 7.43 +/- 0.01; [HCO(3)(-)] =
      26.2 +/- 0.5 mM) medium, with or without 1 microM cortisol (Cort), and net
      calcium efflux and medium prostaglandin E(2) (PGE(2)) levels and osteoclastic
      beta-glucuronidase activity were determined. Compared with Ntl, Cort alone
      decreased calcium efflux, medium PGE(2), and osteoclast activity; Acid led to an
      increase in all three parameters. The addition of Cort to Acid led to a reduction
      of calcium efflux, medium PGE(2) levels and beta-glucuronidase activity compared
      with Acid alone. There was a significant direct correlation between medium PGE(2)
      concentration and net calcium efflux (r = 0.944; n = 23; P < 0.0001), between
      osteoclastic beta-glucuronidase activity and net calcium efflux (r = 0.663; n =
      40; P < 0.001), and between medium PGE(2) concentration and beta-glucuronidase
      activity (r = 0.976; n = 4; P < 0.01). Thus, in vitro cortisol inhibits acid
      induced, cell-mediated osteoclastic bone resorption through a decrease in
      osteoblastic PGE(2) production. These results suggest that the osteopenia
      observed in response to metabolic acidosis in vivo is not due to an increase in
      endogenous cortisol production.

PMID- 12239243
TI  - Modulation of renal calcium handling by 11 beta-hydroxysteroid dehydrogenase type
      2.
AB  - Reduced concentration of serum ionized calcium and increased urinary calcium
      excretion have been reported in primary aldosteronism and glucocorticoid-treated
      patients. A reduced activity of the 11 beta-hydroxysteroid dehydrogenase type 2
      (11 beta HSD2) results in overstimulation of the mineralocorticoid receptor by
      cortisol. Whether inhibition of the 11 beta HSD2 by glycyrrhetinic acid (GA) may
      increase renal calcium excretion is unknown. Serum and urinary electrolyte and
      creatinine, serum ionized calcium, urinary calcium excretion, and the steroid
      metabolites (THF+5 alpha THF)/THE as a parameter of 11 beta HSD2 activity were
      repeatedly measured in 20 healthy subjects during baseline conditions and during
      1 wk of 500 mg/d GA. One week of GA induced a maximal increment of 93% in (THF+5
      alpha THF)/THE. Ambulatory BP was significantly higher at day 7 of GA than at
      baseline (126/77 +/- 10/7 versus 115/73 +/- 8/6 mmHg; P < 0.001 for systolic; P <
      0.05 for diastolic). During GA administration, serum ionized calcium decreased
      from 1.26 +/- 0.05 to 1.18 +/- 0.04 mmol/L (P < 0.0001), and absolute urinary
      calcium excretion was enhanced from 29.2 +/- 3.6 to 31.9 +/- 3.1 micromol/L GFR
      (P < 0.01). Fractional calcium excretion increased from 2.4 +/- 0.3 to 2.7 +/-
      0.3% (P < 0.01) and was negatively correlated to the fractional sodium excretion
      during GA (R = -0.35; P < 0.001). Moreover, serum potassium correlated positively
      with serum ionized calcium (R = 0.66; P < 0.0001). Inhibition of 11 beta HSD2
      activity is sufficient to significantly increase the fractional excretion of
      calcium and decrease serum ionized calcium, suggesting decreased tubular
      reabsorption of this divalent cation under conditions of renal
      glucocorticoid/mineralocorticoid excess. The likely site of steroid-regulated
      renal calcium handling appears to be the distal tubule.

PMID- 12239244
TI  - Comparison between SLC3A1 and SLC7A9 cystinuria patients and carriers: a need for
      a new classification.
AB  - Recent developments in the genetics and physiology of cystinuria do not support
      the traditional classification, which is based on the excretion of cystine and
      dibasic amino acids in obligate heterozygotes. Mutations of only two genes
      (SLC3A1 and SLC7A9), identified by the International Cystinuria Consortium (ICC),
      have been found to be responsible for all three types of the disease. The ICC set
      up a multinational database and collected genetic and clinical data from 224
      patients affected by cystinuria, 125 with full genotype definition. Amino acid
      urinary excretion patterns of 189 heterozygotes with genetic definition and of 83
      healthy controls were also included. All SLC3A1 carriers and 14% of SLC7A9
      carriers showed a normal amino acid urinary pattern (i.e., type I phenotype). The
      rest of the SLC7A9 carriers showed phenotype non-I (type III, 80.5%; type II,
      5.5%). This makes the traditional classification imprecise. A new classification
      is needed: type A, due to two mutations of SLC3A1 (rBAT) on chromosome 2 (45.2%
      in our database); type B, due to two mutations of SLC7A9 on chromosome 19 (53.2%
      in this series); and a possible third type, AB (1.6%), with one mutation on each
      of the above-mentioned genes. Clinical data show that cystinuria is more severe
      in males than in females. The two types of cystinuria (A and B) had a similar
      outcome in this retrospective study, but the effect of the treatment could not be
      analyzed. Stone events do not correlate with amino acid urinary excretion. Renal
      function was clearly impaired in 17% of the patients.

PMID- 12239245
TI  - Effect of increased dialysate volume on peritoneal surface area among peritoneal
      dialysis patients.
AB  - Large dialysate volumes are often required to increase solute clearance for
      peritoneal dialysis patients. The resulting increase in solute clearance might be
      attributable to an increased plasma-to-dialysate concentration gradient and/or to
      an increased effective peritoneal surface area. One of the factors affecting the
      latter is the peritoneal surface area in contact with dialysate (PSA-CD). The aim
      of this study was to estimate the change in PSA-CD after a 50% increase in the
      instilled dialysate volume for patients undergoing peritoneal dialysis. PSA-CD
      was estimated by using a method applying stereologic techniques to computed
      tomographic (CT) scans of the peritoneal space. The peritoneal cavity of 10
      peritoneal dialysis patients was filled with a solution containing dialysate,
      half-isotonic saline solution, and contrast medium. Peritoneal function tests and
      CT scanning of the abdomen were performed twice for each patient (with an
      interval of 1 wk), after instillation of a 2- or 3-L solution. Scanning of thin
      helical CT sections was performed, and 36 random sections of the abdomen were
      obtained after reconstruction. A grid was superimposed on the sections. The
      surface area was estimated by using stereologic methods. After instillation of
      the 2-L solution, the volume of the peritoneal solution at the time of CT
      scanning was 2.32 +/- 0.05 L. The PSA-CD was 0.57 +/- 0.03 m(2), ranging from
      0.41 to 0.76 m(2). The use of the 3-L solution increased the peritoneal volume by
      46 +/- 2%. PSA-CD increased by 18 +/- 2.3% to 0.67 +/- 0.04 m(2) (range, 0.49 to
      0.84 m(2); P < 0.01). Creatinine mass transfer increased from 112 +/- 10 mg to
      142 +/- 11 mg (P < 0.0001). The slope of the change of the plasma-to-dialysate
      creatinine concentration gradient with time decreased from -2.26 +/- 0.23 x 10(
      2) to -1.97 +/- 0.16 x 10(-2) (P = 0.01). K(BD-0) (permeability-surface area
      product or mass area transfer coefficient at time 0 of the dwell) increased from
      10.6 +/- 0.7 to 13.6 +/- 1.2 ml/min (P < 0.02). These data demonstrate that
      increasing the instilled dialysate volume by 50% for peritoneal dialysis patients
      results in significant increases in the PSA-CD and K(BD).

PMID- 12239246
TI  - Graft loss and acute coronary syndromes after renal transplantation in the United
      States.
AB  - The impact of graft loss on acute coronary syndromes (ACS) after renal
      transplantation has not been studied in a national population. It was
      hypothesized that ACS might be more frequent after graft loss, as many of the
      benefits of a functioning allograft on metabolism and volume regulation would be
      lost. Data from the 2000 United States Renal Data System (USRDS) was used to
      conduct an historical cohort study of ACS in 14,237 patients who received renal
      transplants between April 1, 1995, and June 30, 1998, (followed until April 28,
      2000) with valid information from CMS Form 2728, excluding patients with
      hospitalized ACS before renal transplant. Cox nonproportional regression models
      were used to calculate the time-dependent adjusted hazard ratio (AHR) of graft
      loss (censored for death) for time-to-first hospitalization for ACS
      (International Classification of Diseases 9th Modification Diagnosis Codes [ICD9]
      code 410.x or 411.x) occurring after transplant. The incidence of ACS was 12.1
      per 1000 patient-years (PY) in patients after graft loss versus 6.5 per 1000 PY
      after transplantation (excluding patients with graft loss). As a time-dependent
      variable, graft loss had an AHR of 2.54 (95% confidence interval, 1.09 to 5.96; P
      = 0.031 by Cox regression). Other risk factors associated with ACS included
      diabetes, older recipient, and male recipient. Allograft rejection was NS. Renal
      transplant recipients share some of the risk factors for ACS with the general
      population. In addition, graft loss was identified as a unique risk factor for
      ACS in this population.

PMID- 12239247
TI  - The effect of donor gender on graft survival.
AB  - Differences in actuarial graft survival according to donor gender have been
      reported for renal allografts and for cardiac and hepatic allografts, but for the
      latter in small series with limited biostatistical power. Using the large
      database of the Collaborative Transplant Study (CTS), this study is an evaluation
      of graft survival according to donor and recipient gender for renal (n =
      124,911), cardiac (n = 25,432), and hepatic (n = 16,410) transplants.
      Confounders, such as calendar year, geographical area, race, donor and recipient
      age, HLA mismatch, cold ischemia time, and others, as well as interaction terms
      were taken into consideration. Death-censored actuarial renal allograft survival
      from female compared with male donors was less in female recipients and even more
      so in male recipients. The donor gender-associated risk ratio for graft loss was
      1.15 in female recipients and 1.22 in male recipients. The age-gender interaction
      term was statistically significant, the gender effect being more pronounced for
      younger (16 to 45 yr) compared with older (>45 yr) donors. Serum creatinine
      concentrations 1 yr after transplantation were also higher for recipients with
      kidney grafts coming from female donors irrespective of recipient gender. For
      first cardiac transplants, graft survival was inferior when the donor was female
      and the recipient male, but no statistical difference according to donor gender
      was demonstrable in female recipients. For first hepatic transplants overall, no
      significant differences according to donor gender were noted. The proportion of
      recipients who had treatment for rejection crisis during the first year was
      higher for male recipients of kidneys from female donors compared with male
      donors. No difference according to donor gender was demonstrable in female
      recipients. For cardiac and hepatic grafts, no significant effect of donor gender
      on the proportion of patients treated for rejection episodes was noted. The data
      show that adverse effects of female donor gender for different organs is much
      less uniform than reported in the past. An important confounder is donor age. A
      gender effect on graft survival is also observed for cardiac allografts.
      Therefore, in addition to potential "nephron underdosing," further
      pathomechanisms must play a role, possibly differences in immunogenicity
      according to donor gender.

PMID- 12239248
TI  - Dominance of virus-specific CD8 T cells in human primary cytomegalovirus
      infection.
AB  - Cellular immune responses are of high importance in initiating and maintaining
      immunity against virus infections. Whereas the cellular immune response during
      persistent cytomegalovirus (CMV) infection is well assessable, the individual
      contribution of CD4 and CD8 T cell responses during primary infection has not
      been described. A novel whole-blood assay, which relies on the flow-cytometric
      detection of antigen-induced cytokine expression, was used to characterize CMV
      specific CD4 and CD8 T cell responses during primary infection of CMV
      seronegative recipients of a renal allograft from a CMV seropositive donor. These
      T cell responses were compared with long-term CMV-positive patients with known
      history of transplantation-related seroconversion. Results were further
      correlated to CMV load and serum IgG and IgM. The long-term seroconverted
      patients consistently showed a dominant CMV-specific CD4 T cell response (median
      frequencies: CD4, 1.12% [range, 0.35 to 8.10%] versus CD8 0.13% [range, <0.05 to
      0.55%]). In contrast, during primary infection, the cellular immune response is
      strongly dominated by CMV-specific CD8 T cells (median peak frequencies: CD4,
      1.24% [range, 0.21 to 1.60%] versus CD8, 2.47% [range, 1.34 to 6.67%]). Upon
      receipt of ganciclovir, viral load as well as CMV-specific CD8 responses
      decreased. The frequency of the respective CD4 T cells fluctuated during decrease
      of CMV load and became dominant over CMV-specific CD8 T cell responses. These
      results are consistent with the view of an effective direct antiviral activity of
      CD8 T cells, which is most critical during periods of high viremia. Later on
      during persistent infection, CD4 T cells dominate the immune response to support
      the state of antiviral immunity.

PMID- 12239249
TI  - A Monocyte chemoattractant protein-1 (MCP-1) polymorphism and outcome after renal
      transplantation.
AB  - Among the factors modulating transplant rejection and cardiovascular disease,
      chemokines and their respective receptors deserve special attention. In this
      respect, increased expression of MCP-1 and the corresponding receptor CCR2 have
      been demonstrated in renal transplant rejection and coronary artery disease. The
      impact of the MCP-1-2518G and CCR2-64I genotypes on renal allograft function was
      investigated in 232 patients who underwent transplantation over an 11-yr period.
      Genomic DNA was genotyped using PCR with sequence-specific primers followed by
      restriction fragment length polymorphism analysis. Eighteen (7.8%) patients were
      homozygous for the MCP-1-2518G mutation. The G/G allele of MCP-1 -2518 behaved as
      a determinant for long-term allograft survival and resulted in reduction of the
      mean graft survival, as compared with the heterozygous (A/G) or wild-type (A/A)
      allele (67 +/- 14 versus 95 +/- 4 mo; Log rank P = 0.0052). The 64I mutation of
      CCR2 had no effect on kidney graft failure (93 +/- 6 and 91 +/- 5 mo,
      respectively; P = 0.81). None of the investigated polymorphisms showed a
      significant shift in gene frequency in acute rejection and rejection-free groups.
      In conjunction with these findings, peripheral blood mononuclear cells from
      kidney transplant recipients carrying the G-allele were characterized by a 2.5
      fold higher MCP-1 secretion (P < 0.05). In conclusion, recipients of renal
      transplants homozygous for the -2518 G mutation of the MCP-1 gene are at risk for
      premature kidney graft failure. This variant of MCP-1 may be a future predictor
      for long-term kidney graft failure.

PMID- 12239250
TI  - Expanding the donor pool: effect on graft outcome.

PMID- 12239251
TI  - TGF-beta signaling in renal disease.
AB  - Since discovery over a decade ago of a role for the cytokine TGF-beta as key
      mediator of glomerular and tubulointerstitial pathobiology in chronic kidney
      diseases, studies of TGF-beta signaling in the kidney have focused on the
      molecular biology of fibrogenesis. In recent years, glomerular and tubular
      epithelial cell apoptosis and cellular transdifferentiation have been proposed as
      putative primary pathomechanisms that may underlie progression of renal disease.
      This review describes evidence in support of nonlinear models and functional
      roles of TGF-beta signaling in mediating apoptosis and epithelial-to-mesenchymal
      transdifferentiation (EMT) in chronic progressive renal disease. Emphasis is
      placed on cell context-dependent models of TGF-beta signaling providing a
      conceptual framework to consolidate seemingly distinct pathomechanisms of
      progression of glomerular and tubulointerstitial disease.

PMID- 12239252
TI  - Molecular mechanisms of diabetic mesangial cell hypertrophy: a proliferation of
      novel factors.

PMID- 12239253
TI  - Cilia in PKD--letting it all hang out.

PMID- 12239254
TI  - Breast density and the risk of breast cancer.

PMID- 12239255
TI  - Environmental exposure to endotoxin and its relation to asthma in school-age
      children.
AB  - BACKGROUND: In early life, the innate immune system can recognize both viable and
      nonviable parts of microorganisms. Immune activation may direct the immune
      response, thus conferring tolerance to allergens such as animal dander or tree
      and grass pollen. METHODS: Parents of children who were 6 to 13 years of age and
      were living in rural areas of Germany, Austria, or Switzerland where there were
      both farming and nonfarming households completed a standardized questionnaire on
      asthma and hay fever. Blood samples were obtained from the children and tested
      for atopic sensitization; peripheral-blood leukocytes were also harvested from
      the samples for testing. The levels of endotoxin in the bedding used by these
      children were examined in relation to clinical findings and to the cytokine
      production profiles of peripheral-blood leukocytes that had been stimulated with
      lipopolysaccharide and staphylococcal enterotoxin B. Complete data were available
      for 812 children. RESULTS: Endotoxin levels in samples of dust from the child's
      mattress were inversely related to the occurrence of hay fever, atopic asthma,
      and atopic sensitization. Nonatopic wheeze was not significantly associated with
      the endotoxin level. Cytokine production by leukocytes (production of tumor
      necrosis factor alpha, interferon-gamma, interleukin-10, and interleukin-12) was
      inversely related to the endotoxin level in the bedding, indicating a marked down
      regulation of immune responses in exposed children. CONCLUSIONS: A subject's
      environmental exposure to endotoxin may have a crucial role in the development of
      tolerance to ubiquitous allergens found in natural environments.

PMID- 12239256
TI  - Incidence and prognosis of syncope.
AB  - BACKGROUND: Little is known about the epidemiology and prognosis of syncope in
      the general population. METHODS: We evaluated the incidence, specific causes, and
      prognosis of syncope among women and men participating in the Framingham Heart
      Study from 1971 to 1998. RESULTS: Of 7814 study participants followed for an
      average of 17 years, 822 reported syncope. The incidence of a first report of
      syncope was 6.2 per 1000 person-years. The most frequently identified causes were
      vasovagal (21.2 percent), cardiac (9.5 percent), and orthostatic (9.4 percent);
      for 36.6 percent the cause was unknown. The multivariable-adjusted hazard ratios
      among participants with syncope from any cause, as compared with those who did
      not have syncope, were 1.31 (95 percent confidence interval, 1.14 to 1.51) for
      death from any cause, 1.27 (95 percent confidence interval, 0.99 to 1.64) for
      myocardial infarction or death from coronary heart disease, and 1.06 (95 percent
      confidence interval, 0.77 to 1.45) for fatal or nonfatal stroke. The
      corresponding hazard ratios among participants with cardiac syncope were 2.01 (95
      percent confidence interval, 1.48 to 2.73), 2.66 (95 percent confidence interval,
      1.69 to 4.19), and 2.01 (95 percent confidence interval, 1.06 to 3.80).
      Participants with syncope of unknown cause and those with neurologic syncope had
      increased risks of death from any cause, with multivariable-adjusted hazard
      ratios of 1.32 (95 percent confidence interval, 1.09 to 1.60) and 1.54 (95
      percent confidence interval, 1.12 to 2.12), respectively. There was no increased
      risk of cardiovascular morbidity or mortality associated with vasovagal
      (including orthostatic and medication-related) syncope. CONCLUSIONS: Persons with
      cardiac syncope are at increased risk for death from any cause and cardiovascular
      events, and persons with syncope of unknown cause are at increased risk for death
      from any cause. Vasovagal syncope appears to have a benign prognosis.

PMID- 12239257
TI  - Heritability of mammographic density, a risk factor for breast cancer.
AB  - BACKGROUND: Women with extensive dense breast tissue visible on a mammogram have
      a risk of breast cancer that is 1.8 to 6.0 times that of women of the same age
      with little or no density. Menopausal status, weight, and parity account for 20
      to 30 percent of the age-adjusted variation in the percentage of dense tissue.
      METHODS: We undertook two studies of twins to determine the proportion of the
      residual variation in the percentage of density measured by mammography that can
      be explained by unmeasured additive genetic factors (heritability). A total of
      353 pairs of monozygotic twins and 246 pairs of dizygotic twins were recruited
      from the Australian Twin Registry, and 218 pairs of monozygotic twins and 134
      pairs of dizygotic twins were recruited in Canada and the United States.
      Information on putative determinants of breast density was obtained by
      questionnaire. Mammograms were digitized, randomly ordered, and read by a blinded
      investigator. RESULTS: After adjustment for age and measured covariates, the
      correlation coefficient for the percentage of dense tissue was 0.61 for
      monozygotic pairs in Australia, 0.67 for monozygotic pairs in North America, 0.25
      for dizygotic pairs in Australia, and 0.27 for dizygotic pairs in North America.
      According to the classic twin model, heritability (the proportion of variants
      attributable to additive genetic factors) accounted for 60 percent of the
      variation in density (95 percent confidence interval, 54 to 66) in Australian
      twins, 67 percent (95 percent confidence interval, 59 to 75) in North American
      twins, and 63 percent (95 percent confidence interval, 59 to 67) in all twins
      studied. CONCLUSIONS: These results show that the population variation in the
      percentage of dense tissue on mammography at a given age has high heritability.
      Because mammographic density is associated with an increased risk of breast
      cancer, finding the genes responsible for this phenotype could be important for
      understanding the causes of the disease.

PMID- 12239258
TI  - Hemofiltration and peritoneal dialysis in infection-associated acute renal
      failure in Vietnam.
AB  - BACKGROUND: In some parts of the world, peritoneal dialysis is widely used for
      renal replacement in acute renal failure. In resource-rich countries, it has been
      supplanted in recent years by hemodialysis and, most recently, by hemofiltration
      and associated techniques. The relative efficacy of peritoneal dialysis and
      hemofiltration is not known. METHODS: We conducted an open, randomized comparison
      of pumped venovenous hemofiltration and peritoneal dialysis in patients with
      infection-associated acute renal failure in an infectious-disease referral
      hospital in Vietnam. RESULTS: Seventy adult patients with severe falciparum
      malaria (48 patients) or sepsis (22 patients) were enrolled; 34 were assigned to
      hemofiltration and 36 to peritoneal dialysis. The mortality rate was 47 percent
      (17 patients) in the group assigned to peritoneal dialysis, as compared with 15
      percent (5 patients) in the group assigned to hemofiltration (P=0.005). The rates
      of resolution of acidosis and of decline in the serum creatinine concentration in
      the group assigned to hemofiltration were more than twice those in the group
      assigned to peritoneal dialysis (P<0.005), and renal-replacement therapy was
      required for a significantly shorter period. In a multivariate analysis, the odds
      ratio for death was 5.1 (95 percent confidence interval, 1.6 to 16) and that for
      a need for future dialysis was 4.7 (95 percent confidence interval, 1.3 to 17) in
      the group assigned to peritoneal dialysis. The cost of hemofiltration per
      survivor was less than half that of peritoneal dialysis, and the cost per life
      saved was less than one third. CONCLUSIONS: Hemofiltration is superior to
      peritoneal dialysis in the treatment of infection-associated acute renal failure.

PMID- 12239259
TI  - Images in clinical medicine. Ulnar-nerve schwannoma.

PMID- 12239260
TI  - Tinnitus.

PMID- 12239261
TI  - The effect of infections on susceptibility to autoimmune and allergic diseases.

PMID- 12239262
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 29-2002. A 17-year-old boy with acute mitral regurgitation and
      pulmonary edema.

PMID- 12239263
TI  - Eat dirt--the hygiene hypothesis and allergic diseases.

PMID- 12239264
TI  - Syncope--getting to the heart of the matter.

PMID- 12239265
TI  - Peritoneal dialysis in acute renal failure--why the bad outcome?

PMID- 12239266
TI  - ADAM-33 surfaces as an asthma gene.

PMID- 12239267
TI  - Large employers' new strategies in health care.

PMID- 12239268
TI  - High bone density due to a mutation in LDL-receptor-related protein 5.

PMID- 12239269
TI  - Major radiation exposure.

PMID- 12239270
TI  - Diabetic nephropathy.

PMID- 12239271
TI  - Aspirin for the primary prevention of coronary events.

PMID- 12239272
TI  - Assessment of atherosclerotic plaques of the aortic arch.

PMID- 12239273
TI  - Coronary-artery fistula.

PMID- 12239274
TI  - Seizure induced by insufflation of bupropion.

PMID- 12239275
TI  - Changing health insurance trends.

PMID- 12239277
TI  - High throughput peptide mass fingerprinting and protein macroarray analysis using
      chemical printing strategies.
AB  - We describe a chemical printer that uses piezoelectric pulsing for rapid,
      accurate, and non-contact microdispensing of fluid for proteomic analysis of
      immobilized protein macroarrays. We demonstrate protein digestion and peptide
      mass fingerprinting analysis of human plasma and platelet proteins direct from a
      membrane surface subsequent to defined microdispensing of trypsin and matrix
      solutions, hence bypassing multiple liquid-handling steps. Detection of low
      abundance, alkaline proteins from whole human platelet extracts has been
      highlighted. Membrane immobilization of protein permits archiving of samples pre
      /post-analysis and provides a means for subanalysis using multiple chemistries.
      This study highlights the ability to increase sequence coverage for protein
      identification using multiple enzymes and to characterize N-glycosylation
      modifications using a combination of PNGase F and trypsin. We also demonstrate
      microdispensing of multiple serum samples in a quantitative microenzyme-linked
      immunosorbent assay format to rapidly screen protein macroarrays for pathogen
      derived antigens. We anticipate the chemical printer will be a major component of
      proteomic platforms for high throughput protein identification and
      characterization with widespread applications in biomedical and diagnostic
      discovery.

PMID- 12239278
TI  - Histone acetylation and deacetylation: identification of acetylation and
      methylation sites of HeLa histone H4 by mass spectrometry.
AB  - The acetylation isoforms of histone H4 from butyrate-treated HeLa cells were
      separated by C(4) reverse-phase high pressure liquid chromatography and by
      polyacrylamide gel electrophoresis. Histone H4 bands were excised and digested in
      gel with the endoprotease trypsin. Matrix-assisted laser desorption ionization
      time-of-flight mass spectrometry was used to characterize the level of
      acetylation, and nanoelectrospray tandem mass spectrometric analysis of the
      acetylated peptides was used to determine the exact sites of acetylation.
      Although there are 15 acetylation sites possible, only four acetylated peptide
      sequences were actually observed. The tetra-acetylated form is modified at
      lysines 5, 8, 12, and 16, the tri-acetylated form is modified at lysines 8, 12,
      and 16, and the di-acetylated form is modified at lysines 12 and 16. The only
      significant amount of the mono-acetylated form was found at position 16. These
      results are consistent with the hypothesis of a "zip" model whereby acetylation
      of histone H4 proceeds in the direction of from Lys-16 to Lys-5, and
      deacetylation proceeds in the reverse direction. Histone acetylation and
      deacetylation are coordinated processes leading to a non-random distribution of
      isoforms. Our results also revealed that lysine 20 is di-methylated in all
      modified isoforms, as well as the non-acetylated isoform of H4.

PMID- 12239279
TI  - Effect of rosiglitazone on the differential expression of diabetes-associated
      proteins in pancreatic islets of C57Bl/6 lep/lep mice.
AB  - The insulin sensitizer drug, rosiglitazone, has been shown to have a protective
      effect on pancreatic islet cell structure and function in animal models of type 2
      diabetes. The identification of new molecular targets associated both with islet
      cell dysfunction and protection is a crucial research goal. In the present study,
      a proteomics approach has been used to identify such targets. Obese C57Bl/6J
      lep/lep mice and lean littermates were given the insulin sensitizer drug
      BRL49653, rosiglitazone. It normalized the impaired glucose tolerance in lep/lep
      mice but had no significant effect on glucose tolerance in the lean mice.
      Pancreatic islet polypeptides were arrayed by a two-dimensional gel
      electrophoresis system that separated more than 2500 individual spots. Three
      overexpressed and six underexpressed proteins were significant (p < 0.05) between
      lep/lep and lean mice, and four were modulated significantly (p < 0.05) by the
      rosiglitazone treatment of the obese mice. The identity of these differentially
      expressed proteins was made using mass spectrometric analysis and provided
      evidence that differential expression of actin-binding proteins may be an
      important aspect of defective islet function. Rosiglitazone increased
      carboxypeptidase B expression in both lep/lep and normal mice suggesting that
      this might be an independent effect of rosiglitazone that contributes to improved
      insulin processing.

PMID- 12239280
TI  - A mass spectrometry-based proteomic approach for identification of
      serine/threonine-phosphorylated proteins by enrichment with phospho-specific
      antibodies: identification of a novel protein, Frigg, as a protein kinase A
      substrate.
AB  - Although proteins phosphorylated on tyrosine residues can be enriched by
      immunoprecipitation with anti-phosphotyrosine antibodies, it has been difficult
      to identify proteins that are phosphorylated on serine/threonine residues because
      of lack of immunoprecipitating antibodies. In this report, we describe several
      antibodies that recognize phosphoserine/phosphothreonine-containing proteins by
      Western blotting. Importantly, these antibodies can be used to enrich for
      proteins phosphorylated on serine/threonine residues by immunoprecipitation, as
      well. Using these antibodies, we have immunoprecipitated proteins from untreated
      cells or those treated with calyculin A, a serine/threonine phosphatase
      inhibitor. Mass spectrometry-based analysis of bands from one-dimensional gels
      that were specifically observed in calyculin A-treated samples resulted in
      identification of several known serine/threonine-phosphorylated proteins
      including drebrin 1, alpha-actinin 4, and filamin-1. We also identified a
      protein, poly(A)-binding protein 2, which was previously not known to be
      phosphorylated, in addition to a novel protein without any obvious domains that
      we designate as Frigg. Frigg is widely expressed and was demonstrated to be a
      protein kinase A substrate in vitro. We identified several in vivo
      phosphorylation sites by tandem mass spectrometry using Frigg protein
      immunoprecipitated from cells. Our method should be applicable as a generic
      strategy for enrichment and identification of serine/threonine-phosphorylated
      substrates in signal transduction pathways.

PMID- 12239281
TI  - Concomitant determination of absolute values of cellular protein amounts,
      synthesis rates, and turnover rates by quantitative proteome profiling.
AB  - Two-dimensional gel electrophoresis of protein fractions isolated from (35)S
      radiolabeled cells provides qualitative information on intracellular amounts,
      (35)S incorporation rates, protein modifications, and subcellular localizations
      of up to thousands of individual proteins. In this study we extended proteome
      profiling to provide quantitative data on synthesis rates of individual proteins.
      We combined fluorescence detection of radiolabeled proteins with SYPRO ruby(TM)
      staining and subsequent autoradiography of the same gels, thereby quantifying
      protein amounts and (35)S incorporation. To calibrate calculation of absolute
      synthesis rates, we determined the amount and autoradiograph intensity of
      radiolabeled haptoglobin secreted by interleukin-6 pretreated HepG2 cells. This
      allowed us to obtain a standard calibration value for (35)S incorporation per
      autoradiograph intensity unit. This value was used to measure protein synthesis
      rates during time course experiments of heat-shocked U937 cells. We measured the
      increasing amounts of hsp70 and calculated it by integration of the determined
      hsp70 synthesis rates over time. Similar results were obtained by both methods,
      validating our standardization procedure. Based on the assumption that the
      synthesis rate of proteins in a steady state of cell metabolism would essentially
      compensate protein degradation, we calculated biological half-lives of proteins
      from protein amounts and synthesis rates determined from two-dimensional gels.
      Calculated protein half-lives were found close to those determined by pulse-chase
      experiments, thus validating this new method. In conclusion, we devised a method
      to assess quantitative proteome profiles covering determination of individual
      amounts, synthesis, and turnover rates of proteins.

PMID- 12239282
TI  - A genome-wide screen for site-specific DNA-binding proteins.
AB  - We used a biochemical genomics method of assaying Saccharomyces cerevisiae
      proteins, derived from a nearly complete set of glutathione S-transferase
      fusions, to develop an approach that is able to identify proteins that bind to a
      DNA element. Using the upstream activation sequence (UAS) of the promoter for the
      invertase gene, SUC2, we identified both specific and nonspecific binding
      activities, which could be classified based on whether they bound with equivalent
      affinity to a nonspecific DNA competitor. Three transcription factors, Mig1,
      Yer028c, and Rgt1, were found to be binding activities specific to the SUC2 UAS.
      Mig1 and Yer028c had been reported previously to bind to elements within the SUC2
      UAS, validating the ability of the method to identify sequence-specific factors.
      The third activity, Rgt1, had not been reported previously to bind to SUC2.
      Additional gel shift assays narrowed the Rgt1 binding site to the SUC2-B element
      within the SUC2 UAS, which is similar to previously identified Rgt1 binding sites
      present in other genes. In vivo levels of invertase activity in an rgt1Delta
      strain were reduced relative to an isogenic RGT+ strain when these strains were
      grown under inducing (low glucose) conditions, suggesting that Rgt1 may have a
      role in the activated transcription of SUC2. This report demonstrates the
      feasibility of identifying DNA binding activities by rapidly assaying a large
      fraction of the predicted open reading frames of an organism for binding to a
      regulatory DNA motif.

PMID- 12239283
TI  - Characterization of an enteropathogenic bovine calicivirus representing a
      potentially new calicivirus genus.
AB  - Bovine enteric caliciviruses (BEC) are associated with diarrhea in young calves.
      The BEC strains detected in Europe form a third genogroup within the genus
      "Norwalk-like viruses" (NLV) of the family Caliciviridae. In this report, we
      present sequence, clinical, and histological data characterizing a novel
      enteropathogenic BEC strain, NB, detected in fecal specimens from calves in the
      United States. The complete RNA genome of the NB virus is 7,453 bases long and is
      organized into two open reading frames (ORFs). ORF-1 is 2,210 amino acids long
      and encodes a large nonstructural polyprotein contiguous with the major capsid
      protein (VP1), similar to the lagoviruses and "Sapporo-like viruses" (SLV). The
      conserved calicivirus motifs were identified in the nonstructural proteins. ORF-2
      is located at the 3' end of the genome and encodes a small basic protein (VP2) of
      225 amino acids. The 5' and 3' untranslated regions are 74 and 67 bases long,
      respectively. Among caliciviruses, NB virus shows amino acid identities of 14.1
      to 22.6% over the entire ORF-1 nonstructural-protein sequence with NLV, SLV,
      vesivirus, and lagovirus strains, while the overall sequence identity of the
      complete NB VP-1 with other caliciviruses is low, varying between 14.6 and 26.7%.
      Phylogenetic analysis of the complete VP1 protein, including strains from all
      four calicivirus genera, showed the closest grouping of NB virus to be with
      viruses in the genus Lagovirus, which cause liver infections and systemic
      hemorrhage in rabbits. In gnotobiotic calves, however, NB virus elicited only
      diarrhea and intestinal lesions that were most severe in the upper small
      intestine (duodenum and jejunum), similar to the NLV BEC strains. The tissues of
      major organs, including the lung, liver, kidney, and spleen, had no visible
      microscopic lesions.

PMID- 12239284
TI  - Quantitation of human immunodeficiency virus type 1 DNA forms with the second
      template switch in peripheral blood cells predicts disease progression
      independently of plasma RNA load.
AB  - There are several forms of human immunodeficiency virus type 1 (HIV-1) DNA in
      peripheral blood T cells and lymph nodes in untreated HIV-1-infected individuals
      and in patients whose plasma HIV-1 RNA levels are suppressed by long-term
      combination antiretroviral therapy. However, it remains to be established whether
      the concentration of HIV-1 DNA in cells predicts the clinical outcome of HIV-1
      infection. In this report, we measured the concentration of HIV-1 DNA forms which
      has undergone the second template switch (STS DNA) and 2-long-terminal-repeat DNA
      circles in peripheral blood mononuclear cell (PBMC) samples. To do this, we used
      molecular-beacon-based real-time PCR assays and studied 130 patients with
      hemophilia in the Multicenter Hemophilia Cohort Study. We assessed the influence
      of baseline HIV-1 STS DNA levels on the progression of HIV-1 disease in the
      absence of combination antiretroviral therapy by Kaplan-Meier and Cox regression
      analysis. Among the patients who progressed to AIDS, the median levels
      (interquartile ranges) of STS HIV-1 DNA in PBMC were significantly higher than
      those of patients who remained AIDS free during the 16 years of follow-up (1,017
      [235 to 6,059] and 286 [31 to 732] copies per 10(6) PBMC, respectively; P <
      0.0001). Rates of progression to death and development of AIDS varied
      significantly (log rank P < 0.001) by quartile distribution of HIV-1 STS DNA
      levels. After adjustment for age at seroconversion, baseline CD4(+) T-cell
      counts, plasma viral load, and T-cell-receptor excision circles, the relative
      hazards (RH) of death and AIDS were significantly increased with higher HIV-1 STS
      DNA levels (adjusted RH, 1.84 [95% confidence interval (CI), 1.30 to 2.59] and
      2.62 [95% CI, 1.75 to 3.93] per 10-fold increase per 10(6) PBMC, respectively).
      HIV-1 STS DNA levels in each individual remained steady in longitudinal PBMC
      samples during 16 years of follow-up. Our findings show that the concentration of
      HIV-1 STS DNA in PBMC complements the HIV-1 RNA load in plasma in predicting the
      clinical outcome of HIV-1 disease. This parameter may have important implications
      for understanding the virological response to combination antiretroviral therapy.

PMID- 12239285
TI  - Naturally occurring substitutions in the P/V gene convert the noncytopathic
      paramyxovirus simian virus 5 into a virus that induces alpha/beta interferon
      synthesis and cell death.
AB  - The V protein of the paramyxovirus simian virus 5 (SV5) is responsible for
      targeted degradation of STAT1 and the block in alpha/beta interferon (IFN
      alpha/beta) signaling that occurs after SV5 infection of human cells. We have
      analyzed the growth properties of a recombinant SV5 that was engineered to be
      defective in targeting STAT1 degradation. A recombinant SV5 (rSV5-P/V-CPI-) was
      engineered to contain six naturally occurring P/V protein mutations, three of
      which have been shown in previous transfection experiments to disrupt the V
      mediated block in IFN-alpha/beta signaling. In contrast to wild-type (WT) SV5,
      human cells infected with rSV5-P/V-CPI- had STAT1 levels similar to those in mock
      infected cells. Cells infected with rSV5-P/V-CPI- were found to express higher
      than-WT levels of viral proteins and mRNA, suggesting that the P/V mutations had
      disrupted the regulation of viral RNA synthesis. Despite the inability to target
      STAT1 for degradation, single-step growth assays showed that the rSV5-P/V-CPI-
      mutant virus grew better than WT SV5 in all cell lines tested. Unexpectedly,
      cells infected with rSV5-P/V-CPI- but not WT SV5 showed an activation of a
      reporter gene that was under control of the IFN-beta promoter. The secretion of
      IFN from cells infected with rSV5-P/V-CPI- but not WT SV5 was confirmed by a
      bioassay for IFN. The rSV5-P/V-CPI- mutant grew to higher titers than did WT rSV5
      at early times in multistep growth assays. However, rSV5-P/V-CPI- growth quickly
      reached a final plateau while WT rSV5 continued to grow and produced a final
      titer higher than that of rSV5-P/V-CPI- by late times postinfection. In contrast
      to WT rSV5, infection of a variety of cell lines with rSV5-P/V-CPI- induced cell
      death pathways with characteristics of apoptosis. Our results confirm a role for
      the SV5 V protein in blocking IFN signaling but also suggest new roles for the
      P/V gene products in controlling viral gene expression, the induction of IFN
      alpha/beta synthesis, and virus-induced apoptosis.

PMID- 12239286
TI  - Nonspecific nucleoside triphosphatase P4 of double-stranded RNA bacteriophage
      phi6 is required for single-stranded RNA packaging and transcription.
AB  - Bacteriophage phi6 has a segmented double-stranded RNA genome. The genomic single
      stranded RNA (ssRNA) precursors are packaged into a preformed protein capsid, the
      polymerase complex, composed of viral proteins P1, P2, P4, and P7. Packaging of
      the genomic precursors is an energy-dependent process requiring nucleoside
      triphosphates. Protein P4, a nonspecific nucleoside triphosphatase, has
      previously been suggested to be the prime candidate for the viral packaging
      engine, based on its location at the vertices of the viral capsid and its
      biochemical characteristics. In this study we were able to obtain stable
      polymerase complex particles that are completely devoid of P4. Such particles
      were not able to package ssRNA segments and did not display RNA polymerase
      (either minus- or plus-strand synthesis) activity. Surprisingly, a mutation in
      P4, S250Q, which reduced the level of P4 in the particles to about 10% of the
      wild-type level, did not affect RNA packaging activity or change the kinetics of
      packaging. Moreover, such particles displayed minus-strand synthesis activity.
      However, no plus-strand synthesis was observed, suggesting that P4 has a role in
      the plus-strand synthesis reaction also.

PMID- 12239287
TI  - Adaptation of alphaviruses to heparan sulfate: interaction of Sindbis and Semliki
      forest viruses with liposomes containing lipid-conjugated heparin.
AB  - Passage of Sindbis virus (SIN) in BHK-21 cells has been shown to select for virus
      mutants with high affinity for the glycosaminoglycan heparan sulfate (HS). Three
      loci in the viral spike protein E2 (E2:1, E2:70, and E2:114) have been identified
      that mutate during adaptation and independently confer on the virus the ability
      to bind to cell surface HS (W. B. Klimstra, K. D. Ryman, and R. E. Johnston, J.
      Virol. 72:7357-7366, 1998). In this study, we used HS-adapted SIN mutants to
      evaluate a new model system involving target liposomes containing lipid
      conjugated heparin (HepPE) as an HS receptor analog for the virus. HS-adapted
      SIN, but not nonadapted wild-type SIN TR339, interacted efficiently with HepPE
      containing liposomes at neutral pH. Binding was competitively inhibited by
      soluble heparin. Despite the efficient binding of HS-adapted SIN to HepPE
      containing liposomes at neutral pH, there was no fusion under these conditions.
      Fusion did occur, however, at low pH, consistent with cellular entry of the virus
      via acidic endosomes. At low pH, wild-type or HS-adapted SIN underwent fusion
      with liposomes with or without HepPE with similar kinetics, suggesting that
      interaction with the HS receptor analog at neutral pH has little influence on
      subsequent fusion of SIN at low pH. Finally, Semliki Forest virus (SFV), passaged
      frequently on BHK-21 cells, also interacted efficiently with HepPE-containing
      liposomes, indicating that SFV, like other alphaviruses, readily adapts to cell
      surface HS. In conclusion, the liposomal model system presented in this paper may
      serve as a novel tool for the study of receptor interactions and membrane fusion
      properties of HS-interacting enveloped viruses.

PMID- 12239288
TI  - Newcastle disease virus (NDV) marker vaccine: an immunodominant epitope on the
      nucleoprotein gene of NDV can be deleted or replaced by a foreign epitope.
AB  - The nucleoprotein (NP) of Newcastle disease virus (NDV) functions primarily to
      encapsidate the virus genome for the purpose of RNA transcription, replication,
      and packaging. This conserved multifunctional protein is also efficient in
      inducing NDV-specific antibody in chickens. Here, we localized a conserved B-cell
      immunodominant epitope (IDE) spanning residues 447 to 455 and successfully
      generated a recombinant NDV lacking the IDE by reverse genetics. Despite deletion
      of NP residues 443 to 460 encompassing the NP-IDE, the mutant NDV propagated in
      embryonated specific-pathogen-free chicken eggs to a level comparable to that of
      the parent virus. In addition, a B-cell epitope of the S2 glycoprotein of murine
      hepatitis virus (MHV) was inserted in-frame to replace the NP-IDE. Recombinant
      viruses properly expressing the introduced MHV epitope were successfully
      generated, demonstrating that the NP-IDE not only is dispensable for virus
      replication but also can be replaced by foreign sequences. Chickens immunized
      with the hybrid recombinants produced specific antibodies against the S2
      glycoprotein of MHV and completely lacked antibodies directed against the NP-IDE.
      These marked-NDV recombinants, in conjunction with a diagnostic test, enable
      serological differentiation of vaccinated animals from infected animals and may
      be useful tools in ND eradication programs. The identification of a mutation
      permissive region on the NP gene allows a rational approach to the insertion of
      protective epitopes and may be relevant for the design of NDV-based cross
      protective marker vaccines.

PMID- 12239289
TI  - Slowly declining levels of viral RNA and DNA in DNA/recombinant modified vaccinia
      virus Ankara-vaccinated macaques with controlled simian-human immunodeficiency
      virus SHIV-89.6P challenges.
AB  - In a recent vaccine trial, we showed efficient control of a virulent simian-human
      immunodeficiency virus SHIV-89.6P challenge by priming with a Gag-Pol-Env
      expressing DNA and boosting with a Gag-Pol-Env- expressing recombinant-modified
      vaccinia virus Ankara. Here we show that long-term control has been associated
      with slowly declining levels of viral RNA and DNA. In the vaccinated animals both
      viral DNA and RNA underwent an initial rapid decay, which was followed by a lower
      decay rate. Between 12 and 70 weeks postchallenge, the low decay rates have had
      half-lives of about 20 weeks for viral RNA in plasma and viral DNA in peripheral
      blood mononuclear cells and lymph nodes. In vaccinated animals the viral DNA has
      been mostly unintegrated and has appeared to be largely nonfunctional as
      evidenced by a poor ability to recover infectious virus in cocultivation assays,
      even after CD8 depletion. In contrast, in control animals, which have died, viral
      DNA was mostly integrated and a larger proportion appeared to be functional as
      evidenced by the recovery of infectious virus. Thus, to date, control of the
      challenge infection has appeared to improve with time, with the decay rates for
      viral DNA being at the lower end of values reported for patients on highly active
      antiretroviral therapy.

PMID- 12239290
TI  - Magnitude and frequency of cytotoxic T-lymphocyte responses: identification of
      immunodominant regions of human immunodeficiency virus type 1 subtype C.
AB  - A systematic analysis of immune responses on a population level is critical for a
      human immunodeficiency virus type 1 (HIV-1) vaccine design. Our studies in
      Botswana on (i) molecular analysis of the HIV-1 subtype C (HIV-1C) epidemic, (ii)
      frequencies of major histocompatibility complex class I HLA types, and (iii)
      cytotoxic T-lymphocyte (CTL) responses in the course of natural infection allowed
      us to address HIV-1C-specific immune responses on a population level. We analyzed
      the magnitude and frequency of the gamma interferon ELISPOT-based CTL responses
      and translated them into normalized cumulative CTL responses. The introduction of
      population-based cumulative CTL responses reflected both (i) essentials of the
      predominant virus circulating locally in Botswana and (ii) specificities of the
      genetic background of the Botswana population, and it allowed the identification
      of immunodominant regions across the entire HIV-1C. The most robust and vigorous
      immune responses were found within the HIV-1C proteins Gag p24, Vpr, Tat, and
      Nef. In addition, moderately strong responses were scattered across Gag p24, Pol
      reverse transcriptase and integrase, Vif, Tat, Env gp120 and gp41, and Nef.
      Assuming that at least some of the immune responses are protective, these
      identified immunodominant regions could be utilized in designing an HIV vaccine
      candidate for the population of southern Africa. Targeting multiple
      immunodominant regions should improve the overall vaccine immunogenicity in the
      local population and minimize viral escape from immune recognition. Furthermore,
      the analysis of HIV-1C-specific immune responses on a population level represents
      a comprehensive systematic approach in HIV vaccine design and should be
      considered for other HIV-1 subtypes and/or different geographic areas.

PMID- 12239291
TI  - Human immunodeficiency virus-specific CD8(+) T-cell responses do not predict
      viral growth and clearance rates during structured intermittent antiretroviral
      therapy.
AB  - There is a continuing search for better ways to use existing drugs against human
      immunodeficiency virus (HIV). One idea is to use short therapy interruptions to
      "autovaccinate" HIV-infected patients. A group of 13 chronically HIV-infected
      patients enrolled in a trial of such so-called structured treatment interruptions
      (STIs) were intensively studied with respect to their viral load (VL) and HIV
      specific CD8+ T-cell (cytotoxic T-lymphocyte [CTL]) responses. We found that 10
      of the 13 patients had plateau VLs after STIs that were lower than their
      pretreatment VLs. While viral rebound rates became lower over STIs, there were no
      changes in clearance rates. Although numbers of CTLs did increase over the same
      time that viral rebounds decreased, there was no correlation between CTL count
      and either viral rebound rates or clearance rates. Finally, we asked whether
      absolute numbers of or changes in numbers of CTLs predict plateau VLs after STIs.
      No measure of CTLs was able to predict plateau VLs. Thus, there was no signature
      in these data of an important contribution to virological control from HIV
      specific CD8+ T lymphocytes.

PMID- 12239292
TI  - Vesicular stomatitis virus infection alters the eIF4F translation initiation
      complex and causes dephosphorylation of the eIF4E binding protein 4E-BP1.
AB  - Vesicular stomatitis virus (VSV) modulates protein synthesis in infected cells in
      a way that allows the translation of its own 5'-capped mRNA but inhibits the
      translation of host mRNA. Previous data have shown that inactivation of eIF2alpha
      is important for VSV-induced inhibition of host protein synthesis. We tested
      whether there is a role for eIF4F in this inhibition. The multisubunit eIF4F
      complex is involved in the regulation of protein synthesis via phosphorylation of
      cap-binding protein eIF4E, a subunit of eIF4F. Translation of host mRNA is
      significantly reduced under conditions in which eIF4E is dephosphorylated. To
      determine whether VSV infection alters the eIF4F complex, we analyzed eIF4E
      phosphorylation and the association of eIF4E with other translation initiation
      factors, such as eIF4G and the translation inhibitor 4E-BP1. VSV infection of
      HeLa cells resulted in the dephosphorylation of eIF4E at serine 209 between 3 and
      6 h postinfection. This time course corresponded well to that of the inhibition
      of host protein synthesis induced by VSV infection. Cells infected with a VSV
      mutant that is delayed in the ability to inhibit host protein synthesis were also
      delayed in dephosphorylation of eIF4E. In addition to decreasing eIF4E
      phosphorylation, VSV infection also resulted in the dephosphorylation and
      activation of eIF4E-binding protein 4E-BP1 between 3 and 6 h postinfection.
      Analysis of cap-binding complexes showed that VSV infection reduced the
      association of eIF4E with the eIF4G scaffolding subunit at the same time as its
      association with 4E-BP1 increased and that these time courses correlated with the
      dephosphorylation of eIF4E. These changes in the eIF4F complex occurred over the
      same time period as the onset of viral protein synthesis, suggesting that
      activation of 4E-BP1 does not inhibit translation of viral mRNAs. In support of
      this idea, VSV protein synthesis was not affected by the presence of rapamycin, a
      drug that blocks 4E-BP1 phosphorylation. These data show that VSV infection
      results in modifications of the eIF4F complex that are correlated with the
      inhibition of host protein synthesis and that translation of VSV mRNAs occurs
      despite lowered concentrations of the active cap-binding eIF4F complex. This is
      the first noted modification of both eIF4E and 4E-BP1 phosphorylation levels
      among viruses that produce capped mRNA for protein translation.

PMID- 12239293
TI  - Molecular genetic evidence that the hydrophobic anchors of glycoproteins E2 and
      E1 interact during assembly of alphaviruses.
AB  - Chimeric alphaviruses in which the 6K and glycoprotein E1 moieties of Sindbis
      virus are replaced with those of Ross River virus grow very poorly, but upon
      passage, adapted variants arise that grow >100 times better. We have sequenced
      the entire domain encoding the E2, 6K, and E1 proteins of a number of these
      adapted variants and found that most acquired two amino acid changes, which had
      cumulative effects. In three independent passage series, amino acid 380 of E2,
      which is in the transmembrane domain, was mutated from the original isoleucine to
      serine in two instances and to valine once. We have now changed this residue to
      seven others by site-directed mutagenesis and tested the effects of these
      mutations on the growth of both the chimera [SIN(RRE1)] and of parental Sindbis.
      These results indicate that the transmembrane domains of glycoproteins E2 and E1
      of alphaviruses interact in a sequence-dependent manner and that this interaction
      is required for efficient budding and assembly of infectious virions.

PMID- 12239294
TI  - A secondary structure that contains the 5' and 3' splice sites suppresses
      splicing of duck hepatitis B virus pregenomic RNA.
AB  - Pregenomic RNA (pgRNA) plays two major roles in the hepadnavirus life cycle. It
      is the mRNA for two proteins required for DNA replication, C and P, and it is the
      template for reverse transcription. pgRNA is a terminally redundant transcript
      whose synthesis does not involve RNA splicing. For duck hepatitis B virus (DHBV),
      a spliced RNA is derived from pgRNA by removal of a single intron. The mechanism
      for the simultaneous cytoplasmic accumulation of unspliced (pgRNA) and spliced
      RNA was not known. We found that mutations within two regions of the DHBV genome
      reduced the level of pgRNA while increasing the level of spliced RNA. One region
      is near the 5' end of pgRNA (region A), while the second is near the middle of
      pgRNA (region B). Inspection of the DHBV nucleotide sequence indicated that
      region A could base pair with region B. The 5' and 3' splice sites of the intron
      of the spliced RNA are within regions A and B, respectively. Substitutions that
      disrupted the predicted base pairing reduced the accumulation of pgRNA and
      increased the accumulation of spliced RNA. Restoration of base pairing, albeit
      mutant in sequence, resulted in restoration of pgRNA accumulation with a decrease
      in the level of spliced RNA. Our data are consistent with a model in which
      splicing of the pgRNA is suppressed by a secondary structure between regions A
      and B that occludes the splicing machinery from modifying pgRNA.

PMID- 12239295
TI  - Gamma interferon-dependent protection of the mouse upper respiratory tract
      following parenteral immunization with a respiratory syncytial virus G protein
      fragment.
AB  - The protective mechanisms induced in the mouse upper respiratory tract (URT)
      after intraperitoneal immunization with G2Na, a recombinant respiratory syncytial
      virus (RSV) G protein fragment (amino acid residues 130 to 230), were
      investigated. This protection was recently shown to be mediated by CD4(+) T cells
      and to be critically dependent on the cysteines and amino acids 193 and 194 (H.
      Plotnicky-Gilquin, A. Robert, L. Chevalet, J.-F. Haeuw, A. Beck, J.-Y. Bonnefoy,
      C. Brandt, C.-A. Siegrist, T. N. Nguyen, and U. F. Power, J. Virol. 74:3455-3463,
      2000). On G2Na, we identified a domain (amino acid residues 182 to 198)
      responsible for the T-helper-cell activity. This region coincided with a peptide
      designed AICK (residues 184 to 198) which includes the previously identified
      murine and human T-helper-cell epitope on the native G protein (P. W. Tebbey, M.
      Hagen, and G. E. Hancock, J. Exp. Med. 188:1967-1972, 1998). Immunization with
      AICK, in alum or complete Freund's adjuvant, significantly reduced nasal RSV
      titers in normal BALB/c mice. However, although lung protection was induced, in
      contrast to the case with live RSV, neither AICK nor G2Na was able to prevent
      nasal infection in gamma interferon (IFN-gamma)-knockout mice. Anti-IFN-gamma
      neutralizing antibodies partially inhibited URT protection after administration
      to G2Na-immunized BALB/c mice. Furthermore, while purified CD4(+) T cells from
      BALB/c mice immunized with G2Na or AICK significantly reduced lung and nasal
      infection of naive recipient mice after adoptive transfer, the cells from IFN
      gamma-knockout mice had no effect. Together, these results demonstrated for the
      first time that the T-helper-cell epitope of RSV G protein induces URT protection
      in mice after parenteral immunization through a Th1-type, IFN-gamma-dependent
      mechanism.

PMID- 12239296
TI  - RU5 of Mason-Pfizer monkey virus 5' long terminal repeat enhances cytoplasmic
      expression of human immunodeficiency virus type 1 gag-pol and nonviral reporter
      RNA.
AB  - Retroviruses utilize an unspliced version of their primary transcription product
      as an RNA template for synthesis of viral Gag and Pol structural and enzymatic
      proteins. Cytoplasmic expression of the gag-pol RNA is achieved despite the lack
      of intron removal and the presence of a long and highly structured 5'
      untranslated region that inhibits efficient ribosome scanning. In this study, we
      have identified for the first time that the 5' long terminal repeat (LTR) of
      Mason-Pfizer monkey virus (MPMV) facilitates Rev/Rev-responsive element
      independent expression of HIV-1 gag-pol reporter RNA. The MPMV RU5 region of the
      LTR is necessary and directs functional interaction with cellular
      posttranscriptional modulators present in human 293 and monkey COS cells but not
      in quail QT-6 cells and does not require any viral protein. Deletion of MPMV RU5
      decreases the abundance of spliced mRNA but has little effect on cytoplasmic
      accumulation of unspliced gag-pol RNA despite complete elimination of detectable
      Gag protein production. MPMV RU5 also exerts a positive effect on the cytoplasmic
      expression of intronless luc RNA, and ribosomal profile analysis demonstrates
      that MPMV RU5 directs subcellular localization of the luc transcript to
      polyribosomes. Our findings have a number of similarities with those of reports
      on 5' terminal posttranscriptional control elements in spleen necrosis virus and
      human foamy virus RNA and support the model that divergent retroviruses share 5'
      terminal RNA elements that interact with host proteins to program retroviral RNA
      for productive cytoplasmic expression.

PMID- 12239297
TI  - Study of antigen-processing steps reveals preferences explaining differential
      biological outcomes of two HLA-A2-restricted immunodominant epitopes from human
      immunodeficiency virus type 1.
AB  - Cytotoxic T-lymphocyte (CTL) responses directed to different human
      immunodeficiency virus (HIV) epitopes vary in their protective efficacy. In
      particular, HIV-infected cells are much more sensitive to lysis by anti
      Gag/p17(77-85)/HLA-A2 than to that by anti-polymerase/RT(476-484)/HLA-A2 CTL,
      because of a higher density of p17(77-85) complexes. This report describes
      multiple processing steps favoring the generation of p17(77-85) complexes: (i)
      the exact COOH-terminal cleavage of epitopes by cellular proteases occurred
      faster and more frequently for p17(77-85) than for RT(476-484), and (ii) the
      binding efficiency of the transporter associated with antigen processing was
      greater for p17(77-85) precursors than for the RT(476-484) epitope. Surprisingly,
      these peptides, which differed markedly in their antigenicity, displayed
      qualitatively and quantitatively similar immunogenicity, suggesting differences
      in the mechanisms governing these phenomena. Here, we discuss the mechanisms
      responsible for such differences.

PMID- 12239298
TI  - Replacement of the P1 amino acid of human immunodeficiency virus type 1 Gag
      processing sites can inhibit or enhance the rate of cleavage by the viral
      protease.
AB  - Processing of the human immunodeficiency virus type 1 (HIV-1) Gag precursor is
      highly regulated, with differential rates of cleavage at the five major
      processing sites to give characteristic processing intermediates. We examined the
      role of the P1 amino acid in determining the rate of cleavage at each of these
      five sites by using libraries of mutants generated by site-directed mutagenesis.
      Between 12 and 17 substitution mutants were tested at each P1 position in Gag,
      using recombinant HIV-1 protease (PR) in an in vitro processing reaction of
      radiolabeled Gag substrate. There were three sites in Gag (MA/CA, CA/p2, NC/p1)
      where one or more substitutions mediated enhanced rates of cleavage, with an
      enhancement greater than 60-fold in the case of NC/p1. For the other two sites
      (p2/NC, p1/p6), the wild-type amino acid conferred optimal cleavage. The order of
      the relative rates of cleavage with the P1 amino acids Tyr, Met, and Leu suggests
      that processing sites can be placed into two groups and that the two groups are
      defined by the size of the P1' amino acid. These results point to a trans effect
      between the P1 and P1' amino acids that is likely to be a major determinant of
      the rate of cleavage at the individual sites and therefore also a determinant of
      the ordered cleavage of the Gag precursor.

PMID- 12239299
TI  - Characterization of the putative replisome organizer of the lactococcal
      bacteriophage r1t.
AB  - Analysis of the nucleotide sequence of the genome of the lactococcal
      bacteriophage r1t showed that it may encode at least two proteins involved in DNA
      replication. On the basis of its similarity with the G38P protein encoded by the
      Bacillus subtilis phage SPP1, the product of orf11 (Pro11) is thought to be
      involved in the initiation of phage DNA replication. This protein was
      overexpressed in Lactococcus lactis and partially purified. Gel retardation
      analysis using various r1t DNA fragments indicates that Pro11 specifically binds
      to a sequence located within its cognate gene. DNase I footprinting showed that
      Pro11 protects a stretch of DNA of 47 bp. This region spans four 6-bp short
      direct repeats, which suggests that the region contains four binding sites for
      Pro11. 1,10-Phenanthroline-copper footprinting confirmed the protection of the
      hexamers. An asymmetric protection pattern of each strand was observed,
      suggesting that Pro11 contacts each DNA strand separately at contiguous hexamers.
      We propose a model for the binding of Pro11 to its target sites that may account
      for the torsion strain required for strand opening at the origin of replication.

PMID- 12239300
TI  - A P22 scaffold protein mutation increases the robustness of head assembly in the
      presence of excess portal protein.
AB  - Bacteriophage with linear, double-stranded DNA genomes package DNA into
      preassembled protein shells called procapsids. Located at one vertex in the
      procapsid is a portal complex composed of a ring of 12 subunits of portal
      protein. The portal complex serves as a docking site for the DNA packaging
      enzymes, a conduit for the passage of DNA, and a binding site for the phage tail.
      An excess of the P22 portal protein alters the assembly pathway of the procapsid,
      giving rise to defective procapsid-like particles and aberrant heads. In the
      present study, we report the isolation of escape mutant phage that are able to
      replicate more efficiently than wild-type phage in the presence of excess portal
      protein. The escape mutations all mapped to the same phage genome segment
      spanning the portal, scaffold, coat, and open reading frame 69 genes. The
      mutations present in five of the escape mutants were determined by DNA
      sequencing. Interestingly, each mutant contained the same mutation in the
      scaffold gene, which changes the glycine at position 287 to glutamate. This
      mutation alone conferred an escape phenotype, and the heads assembled by phage
      harboring only this mutation had reduced levels of portal protein and exhibited
      increased head assembly fidelity in the presence of excess portal protein.
      Because this mutation resides in a region of scaffold protein necessary for coat
      protein binding, these findings suggest that the P22 scaffold protein may define
      the portal vertices in an indirect manner, possibly by regulating the fidelity of
      coat protein polymerization.

PMID- 12239301
TI  - High levels of viral replication contrast with only transient changes in CD4(+)
      and CD8(+) cell numbers during the early phase of experimental infection with
      simian immunodeficiency virus SIVmnd-1 in Mandrillus sphinx.
AB  - Early events during human immunodeficiency virus infections are considered to
      reflect the capacity of the host to control infection. We have studied early
      virus and host parameters during the early phase of simian immunodeficiency virus
      SIVmnd-1 nonpathogenic infection in its natural host, Mandrillus sphinx. Four
      mandrills were experimentally infected with a primary SIVmnd-1 strain derived
      from a naturally infected mandrill. Two noninfected control animals were
      monitored in parallel. Blood and lymph nodes were collected at three time points
      before infection, twice a week during the first month, and at days 60, 180, and
      360 postinfection (p.i.). Anti-SIVmnd-1 antibodies were detected starting from
      days 28 to 32 p.i. Neither elevated temperature nor increased lymph node size
      were observed. The viral load in plasma peaked between days 7 to 10 p.i. (2 x
      10(6) to 2 x 10(8) RNA equivalents/ml). Viremia then decreased 10- to 1,000-fold,
      reaching the viral set point between days 30 to 60 p.i. The levels during the
      chronic phase of infection were similar to that in the naturally infected donor
      mandrill (2 x 10(5) RNA equivalents/ml). The CD4(+) cell numbers and percentages
      in blood and lymph nodes decreased slightly (<10%) during primary infection, and
      CD8(+) cell numbers increased transiently. All values returned to preinfection
      infection levels by day 30 p.i. CD8(+) cell numbers or percentages, in peripheral
      blood and lymph nodes, did not increase during the 1 year of follow-up. In
      conclusion, SIVmnd-1 has the capacity for rapid and extensive replication in
      mandrills. Despite high levels of viremia, CD4(+) and CD8(+) cell numbers
      remained stable in the post-acute phase of infection, raising questions regarding
      the susceptibility of mandrill T cells to activation and/or cell death in
      response to SIVmnd-1 infection in vivo.

PMID- 12239302
TI  - Mimovirus: a novel form of vaccine that induces hepatitis B virus-specific
      cytotoxic T-lymphocyte responses in vivo.
AB  - CD8(+) cytotoxic T lymphocytes (CTLs) are now recognized as important mediators
      of immunity against intracellular pathogens, including human immunodeficiency
      virus and tumors. How to efficiently evoke antigen-specific CTL responses in vivo
      has become a crucial problem in the development of modern vaccines. Here, we
      developed a completely novel CTL vaccine-mimovirus, which is a kind of virus-size
      particulate antigen delivery system. It was formed by the self-assembly of a
      cationic peptide containing 18 lysines and a CTL-epitope peptide of HBsAg(28-39),
      with a plasmid encoding mouse interleukin-12 (IL-12) through electrostatic
      interactions. We examined the formation of mimovirus by DNA retardation assay,
      DNase I protection assay, and transmission electron microscopy and demonstrated
      that mimovirus could efficiently transfer the plasmid encoding IL-12 into
      mammalian cells such as P815 cells in vitro. Furthermore, it was proved that
      mimovirus could induce an HBsAg(28-39)-specific CTL response in vivo. Considering
      its effectiveness, flexibility, and defined composition, mimovirus is potentially
      a novel system for vaccination against intracellular pathogens and tumors.

PMID- 12239303
TI  - Evidence against a simple tethering model for enhancement of herpes simplex virus
      DNA polymerase processivity by accessory protein UL42.
AB  - The DNA polymerase holoenzyme of herpes simplex virus type 1 (HSV-1) is a stable
      heterodimer consisting of a catalytic subunit (Pol) and a processivity factor
      (UL42). HSV-1 UL42 differs from most DNA polymerase processivity factors in
      possessing an inherent ability to bind to double-stranded DNA. It has been
      proposed that UL42 increases the processivity of Pol by directly tethering it to
      the primer and template (P/T). To test this hypothesis, we took advantage of the
      different sensitivities of Pol and Pol/UL42 activities to ionic strength.
      Although the activity of Pol is inhibited by salt concentrations in excess of 50
      mM KCl, the activity of the holoenzyme is relatively refractory to changes in
      ionic strength from 50 to 125 mM KCl. We used nitrocellulose filter-binding
      assays and real-time biosensor technology to measure binding affinities and
      dissociation rate constants of the individual subunits and holoenzyme for a short
      model P/T as a function of the ionic strength of the buffer. We found that as
      observed for activity, the binding affinity and dissociation rate constant of the
      Pol/UL42 holoenzyme for P/T were not altered substantially in high- versus low
      ionic-strength buffer. In 50 mM KCl, the apparent affinity with which UL42 bound
      the P/T did not differ by more than twofold compared to that observed for Pol or
      Pol/UL42 in the same low-ionic-strength buffer. However, increasing the ionic
      strength dramatically decreased the affinity of UL42 for P/T, such that it was
      reduced more than 3 orders of magnitude from that of Pol/UL42 in 125 mM KCl. Real
      time binding kinetics revealed that much of the reduced affinity could be
      attributable to an extremely rapid dissociation of UL42 from the P/T in high
      ionic-strength buffer. The resistance of the activity, binding affinity, and
      stability of the holoenzyme for the model P/T to increases in ionic strength,
      despite the low apparent affinity and poor stability with which UL42 binds the
      model P/T in high concentrations of salt, suggests that UL42 does not simply
      tether the Pol to DNA. Instead, it is likely that conformational alterations
      induced by interaction of UL42 with Pol allow for high-affinity and high
      stability binding of the holoenzyme to the P/T even under high-ionic-strength
      conditions.

PMID- 12239304
TI  - Promoter sequences required for reactivation of Epstein-Barr virus from latency.
AB  - A luciferase reporter system with stably transfected oriP plasmids in Akata
      Burkitt's lymphoma cells provides a quantitative assay for the BZLF1 Zp promoter
      in response to B-cell receptor (BCR) activation by cross-linking with anti
      immunoglobulin. In this system, detailed kinetic studies of promoter activity are
      possible. Previously reported promoter elements upstream of -221 from the
      transcription start and the ZIIR sequence had little effect on the Zp promoter,
      but the ZI and ZIIIA elements were essential for early activation. The ZIIIB
      element mediates autoactivation. Mutation of the ZV repressor sequence greatly
      increased the induction of the promoter but did not make it constitutively
      active. Zp transcription in response to BCR cross-linking declined after a few
      hours; this decline was reduced and delayed by acyclovir or phosphonoacetic acid,
      indicating that viral DNA replication or a late viral gene can play a role in the
      switch off of the Zp promoter. Late expression of the LMP1 protein may account
      for this.

PMID- 12239305
TI  - Signal Transduction and Transcription Factor Modification during Reactivation of
      Epstein-Barr Virus from Latency.
AB  - Reactivation of Epstein-Barr virus (EBV) from latency involves activation of the
      Zp promoter of the EBV BZLF1 gene. This occurs rapidly and efficiently in
      response to cross-linking the B-cell receptor on Akata Burkitt's lymphoma cells.
      After optimizing conditions for induction, signal transduction responses to B
      cell receptor cross-linking were observed within 10 min, well before any
      autoactivation effects of BZLF1 protein. The primary events in reactivation were
      shown to involve dephosphorylation of the myocyte enhancer factor 2D (MEF-2D)
      transcription factor via the cyclosporin A-sensitive, calcium-mediated signaling
      pathway. This and other signal transduction events were correlated with the
      quantitative promoter analysis reported in the accompanying paper (U. K. Binne,
      W. Amon, and P. J. Farrell, this issue). Dephosphorylation of MEF-2D is known to
      be associated with histone acetylase recruitment, correlating with the histone
      acetylation at Zp during reactivation that we reported previously (Jenkins et
      al., J. Virol. 74:710-720, 2000). Histone deacetylation in response to
      phosphorylated MEF-2D can be mediated by class I or class II histone deacetylases
      (HDACs); HDAC 7 was the most readily detected class II HDAC in Akata and Raji
      cells, suggesting that it may be involved in Zp repression during latency.

PMID- 12239306
TI  - Addition of a single gp120 glycan confers increased binding to dendritic cell
      specific ICAM-3-grabbing nonintegrin and neutralization escape to human
      immunodeficiency virus type 1.
AB  - The potential role of dendritic cell-specific ICAM-3-grabbing nonintegrin (DC
      SIGN) binding in human immunodeficiency virus transmission across the mucosal
      barrier was investigated by assessing the ability of simian-human
      immunodeficiency chimeric viruses (SHIVs) showing varying degrees of mucosal
      transmissibility to bind the DC-SIGN expressed on the surface of transfected
      cells. We found that gp120 of the highly transmissible, pathogenic CCR5-tropic
      SHIV(SF162P3) bound human and rhesus DC-SIGN with an efficiency threefold or
      greater than that of gp120 of the nonpathogenic, poorly transmissible parental
      SHIV(SF162), and this increase in binding to the DC-SIGN of the SHIV(SF162P3)
      envelope gp120 translated into an enhancement of T-cell infection in trans. The
      presence of an additional glycan at the N-terminal base of the V2 loop of
      SHIV(SF162P3) gp120 compared to that of the parental virus was shown to be
      responsible for the increase in binding to DC-SIGN. Interestingly, this glycan
      also conferred escape from autologous neutralization, raising the possibility
      that the modification occurred as a result of immune selection. Our data suggest
      that more-efficient binding of envelope gp120 to DC-SIGN could be relevant to the
      enhanced mucosal transmissibility of SHIV(SF162P3) compared to that of parental
      SHIV(SF162).

PMID- 12239307
TI  - The NS2 proteins of parvovirus minute virus of mice are required for efficient
      nuclear egress of progeny virions in mouse cells.
AB  - The small nonstructural NS2 proteins of parvovirus minute virus of mice (MVMp)
      were previously shown to interact with the nuclear export receptor Crm1. We
      report here the analysis of two MVM mutant genomic clones generating NS2 proteins
      that are unable to interact with Crm1 as a result of amino acid substitutions
      within their nuclear export signal (NES) sequences. Upon transfection of human
      and mouse cells, the MVM-NES21 and MVM-NES22 mutant genomic clones were
      proficient in synthesis of the four virus-encoded proteins. While the MVM-NES22
      clone was further able to produce infectious mutant virions, no virus could be
      recovered from cells transfected with the MVM-NES21 clone. Whereas the defect of
      MVM-NES21 appeared to be complex, the phenotype of MVM-NES22 could be traced back
      to a novel distinct NS2 function. Infection of mouse cells with the MVM-NES22
      mutant led to stronger nuclear retention not only of the NS2 proteins but also of
      infectious progeny MVM particles. This nuclear sequestration correlated with a
      severe delay in the release of mutant virions in the medium and with prolonged
      survival of the infected cell populations compared with wild-type virus-treated
      cultures. This defect could explain, at least in part, the small size of the
      plaques generated by the MVM-NES22 mutant when assayed on mouse indicator cells.
      Altogether, our data indicate that the interaction of MVMp NS2 proteins with the
      nuclear export receptor Crm1 plays a critical role at a late stage of the
      parvovirus life cycle involved in release of progeny viruses.

PMID- 12239308
TI  - Functional dissection of latency-associated nuclear antigen 1 of Kaposi's sarcoma
      associated herpesvirus involved in latent DNA replication and transcription of
      terminal repeats of the viral genome.
AB  - Latency-associated nuclear antigen 1 (LANA1) of Kaposi's sarcoma-associated
      herpesvirus (KSHV) is implicated in the maintenance of the viral genome during
      latent infection. LANA1 colocalizes with KSHV episomes on the host chromosome and
      mediates their maintenance by attaching these viral structures to host
      chromosomes. Data from long-term selection of drug resistance in cells conferred
      by plasmids containing the terminal repeat (TR) sequence of KSHV revealed that
      KSHV TRs and LANA1 act as cis and trans elements of viral latent replication,
      respectively. In this study, we further characterized the cis- and trans-acting
      elements of KSHV latent replication by using a transient replication assay with a
      methylation-sensitive restriction enzyme, DpnI. Transient reporter and
      replication assays disclosed that the orientation and basal transcriptional
      activity of TR constructs did not significantly affect the efficiency of
      replication. However, at least two TR units were necessary for efficient
      replication. The N-terminal 90 amino acids comprising the chromosome-binding
      domain of LANA1 were required for the mediation of LANA1 C-terminal DNA-binding
      and dimerization domains to support the transient replication of KSHV TRs. LANA1
      interacted with components of the origin recognition complexes (ORCs), similar to
      Epstein-Barr virus nuclear antigen 1. Our data suggest that LANA1 recruits ORCs
      to KSHV TRs for latent replication of the viral genome.

PMID- 12239309
TI  - Mice deficient in perforin, CD4+ T cells, or CD28-mediated signaling maintain the
      typical immunodominance hierarchies of CD8+ T-cell responses to influenza virus.
AB  - CD8 T-cell (T(CD8+)) responses elicited by viral infection demonstrate the
      phenomenon of immunodominance: the numbers of T(CD8+) responding to different
      viral peptides vary over a wide range in a reproducible manner for individuals
      with the same major histocompatibility complex class I alleles. To better
      understand immunodominance, we examined T(CD8+) responses to multiple defined
      viral peptides following infection of mice with influenza virus. The
      immunodominance hierarchy of influenza virus-specific T(CD8+) was not greatly
      perturbed by the absence of either perforin or T-helper cells or by interference
      with B7 (CD80)-mediated signaling. These findings indicate that costimulation by
      antigen-presenting cells (APCs) or killing of APCs by T(CD8+) plays only a minor
      role in establishing the immunodominance hierarchy of antiviral T(CD8+) in this
      system. This points to intrinsic features of the T(CD8+) repertoire as major
      contributors to immunodominance.

PMID- 12239310
TI  - Phenotypic and functional alterations of dendritic cells induced by human
      herpesvirus 6 infection.
AB  - Human herpesvirus 6 (HHV-6) has a tropism for T lymphocytes and
      monocytes/macrophages, suggesting that HHV-6 infection affects the
      immunosurveillance system. In the present study, we investigated the HHV-6
      induced phenotypic and functional alterations of dendritic cells (DCs), which are
      professional antigen-presenting cells. HHV-6 infection of monocyte-derived
      immature DCs appeared to induce the up-regulation of CD80, CD83, CD86, and HLA
      class I and class II molecules, suggesting that HHV-6 infection induces the
      maturation of DCs. In addition, the antigen capture capacity of DCs was found to
      decrease following infection with HHV-6. In contrast to up-regulation of mature
      DC-associated surface molecules on HHV-6-infected DCs, their capacity for
      presentation of alloantigens and exogenous virus antigens to T lymphocytes
      decreased significantly from that of uninfected DCs. In contrast, there appeared
      to be no reduction in the capacity for presentation of an HLA class II-binding
      peptide to the peptide-specific CD4(+) T lymphocytes. These data indicate that
      HHV-6 infection induces phenotypic alterations and impairs the antigen
      presentation capacity of DCs. The present data also suggest that the dysfunction
      of HHV-6-infected DCs is attributable mainly to impairment of the antigen capture
      and intracellular antigen-processing pathways.

PMID- 12239311
TI  - Exchange of the C-terminal part of VP3 from very virulent infectious bursal
      disease virus results in an attenuated virus with a unique antigenic structure.
AB  - Infectious bursal disease virus (IBDV) is the major viral pathogen in the poultry
      industry. Live attenuated serotype 1 vaccine strains are commonly used to protect
      susceptible chickens during their first 6 weeks of life. Wild-type serotype 1
      IBDV strains are highly pathogenic only in chickens, whereas serotype 2 strains
      are apathogenic in chickens and other birds. Here we describe the replacement of
      the genomic double-stranded RNA (dsRNA) encoding the N- or C-terminal part of VP3
      of serotype 1 very virulent IBDV (vvIBDV) (isolate D6948) with the corresponding
      part of serotype 2 (isolate TY89) genomic dsRNA. The modified virus containing
      the C-terminal part of serotype 2 VP3 significantly reduced the virulence in
      specific-pathogen-free chickens, without affecting the distinct bursa tropism of
      serotype 1 IBDV strains. Furthermore, by using serotype-specific antibodies we
      were able to distinguish bursas infected with wild-type vvIBDV from bursas
      infected with the modified vvIBDV. We are currently evaluating the potential of
      this recombinant strain as an attenuated live vaccine that induces a unique
      serological response (i.e., an IBDV marker vaccine).

PMID- 12239312
TI  - Role for human immunodeficiency virus type 1 membrane cholesterol in viral
      internalization.
AB  - The membrane of human immunodeficiency virus type 1 (HIV-1) virions contains high
      levels of cholesterol and sphingomyelin, an enrichment that is explained by the
      preferential budding of the virus through raft microdomains of the plasma
      membrane. Upon depletion of cholesterol from HIV-1 virions with methyl-beta
      cyclodextrin, infectivity was almost completely abolished. In contrast, this
      treatment had only a mild effect on the infectiousness of particles pseudotyped
      with the G envelope of vesicular stomatitis virus. The cholesterol-chelating
      compound nystatin had a similar effect. Cholesterol-depleted HIV-1 virions
      exhibited wild-type patterns of viral proteins and contained normal levels of
      cyclophilin A and glycosylphosphatidylinositol-anchored proteins. Nevertheless,
      and although they could still bind target cells, these virions were markedly
      defective for internalization. These results indicate that the cholesterol
      present in the HIV-1 membrane plays a prominent role in the fusion process that
      is key to viral entry and suggest that drugs capable of disturbing the lipid
      composition of virions could serve as a basis for the development of
      microbicides.

PMID- 12239313
TI  - Sequential localization of two herpes simplex virus tegument proteins to punctate
      nuclear dots adjacent to ICP0 domains.
AB  - The subcellular localization of herpes simplex virus tegument proteins during
      infection is varied and complex. By using viruses expressing tegument proteins
      tagged with fluorescent proteins, we previously demonstrated that the major
      tegument protein VP22 exhibits a cytoplasmic localization, whereas the major
      tegument protein VP13/14 localizes to nuclear replication compartments and
      punctate domains. Here, we demonstrate the presence of a second minor population
      of VP22 in nuclear dots similar in appearance to those formed by VP13/14. We have
      constructed the first-described doubly fluorescence-tagged virus expressing VP22
      and VP13/14 as fusion proteins with cyan fluorescent protein and yellow
      fluorescent protein, respectively. Visualization of both proteins within the same
      live infected cells has indicated that these two tegument proteins localize to
      the same nuclear dots but that VP22 appears there earlier than VP13/14. Further
      studies have shown that these tegument-specific dots are detectable as phase
      dense bodies as early as 2 h after infection and that they are different from the
      previously described nuclear domains that contain capsid proteins. They are also
      different from the ICP0 domains formed at cellular nuclear domain 10 sites early
      in infection but, in almost all cases, are located in juxtaposition to these ICP0
      domains. Hence, these tegument proteins join a growing number of proteins that
      are targeted to discrete nuclear domains in the herpesvirus-infected cell
      nucleus.

PMID- 12239314
TI  - Human T-cell lymphotropic virus type 1 p12(I) expression increases cytoplasmic
      calcium to enhance the activation of nuclear factor of activated T cells.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1) establishes persistent infection
      and is associated with lymphoproliferative or neurodegenerative diseases. As a
      complex retrovirus, HTLV-1 contains typical structural and enzymatic genes, as
      well as regulatory and accessory genes encoded in the pX region. The early events
      necessary for HTLV-1 to establish infection in lymphocytes, its primary target
      cells, remain unresolved. Recent studies have demonstrated the importance of
      regulatory and accessory gene products in determining this virus-host
      interaction. Among these, pX open reading frame I, which encodes two proteins,
      p12(I) and p27(I), is required for establishing persistent infection in vivo and
      for infection in quiescent primary lymphocytes. In addition, p12(I) localizes in
      the endoplasmic reticulum (ER) and cis-Golgi apparatus and associates with a
      calcium binding protein, calreticulin. We recently reported that p12(I)
      expression induces the calcium-responsive T-cell transcription factor, nuclear
      factor of activated T cells (NFAT), in the presence of phorbol ester activation.
      Based on these studies, we hypothesize that p12(I) may modulate calcium release
      from the ER. Here, we report that p12(I) expression increases basal cytoplasmic
      calcium and concurrently diminishes calcium available for release from the ER
      stores. Overexpression of calreticulin, a calcium buffer protein, blocked p12(I)
      mediated NFAT activation independently of its ability to bind p12(I). Chemical
      inhibition studies using inhibitors of inositol 1,4,5-triphosphate receptor and
      calcium release-activated calcium channels suggest that inositol 1,4,5
      triphosphate receptor in the ER membrane and calcium release-activated calcium
      channels in the plasma membrane contribute to p12(I)-mediated NFAT activation.
      Collectively, our results are the first to demonstrate the role of p12(I) in
      elevating cytoplasmic calcium, an antecedent to T-cell activation, and further
      support the important role of this accessory protein in the early events of HTLV
      1 infection.

PMID- 12239315
TI  - A structural model of pestivirus E(rns) based on disulfide bond connectivity and
      homology modeling reveals an extremely rare vicinal disulfide.
AB  - E(rns) is a pestivirus envelope glycoprotein and is the only known viral surface
      protein with RNase activity. E(rns) is a disulfide-linked homodimer of 100 kDa;
      it is found on the surface of pestivirus-infected cells and is secreted into the
      medium. In this study, the disulfide arrangement of the nine cysteines present in
      the mature dimer was established by analysis of the proteolytically cleaved
      protein. Fragments were obtained after digestion with multiple proteolytic
      enzymes and subsequently analyzed by liquid chromatography-electrospray
      ionization mass spectrometry. The analysis demonstrates which cysteine is
      involved in dimerization and reveals an extremely rare vicinal disulfide bridge
      of unknown function. With the assistance of the disulfide arrangement, a three
      dimensional model was built by homology modeling based on the alignment with
      members of the Rh/T2/S RNase family. Compared to these other RNase family
      members, E(rns) shows an N-terminal truncation, a large insertion of a cystine
      rich region, and a C-terminal extension responsible for membrane translocation.
      The homology to mammalian RNase 6 supports a possible role of E(rns) in B-cell
      depletion.

PMID- 12239316
TI  - BCL-2 and BAX protect adult mice from lethal Sindbis virus infection but do not
      protect spinal cord motor neurons or prevent paralysis.
AB  - Cellular proteins that regulate apoptotic cell death can modulate the outcome of
      Sindbis virus (SV) encephalitis in mice. Both endogenous and overexpressed BCL-2
      and BAX proteins protect newborn mice from fatal SV infection by blocking
      apoptosis in infected neurons. To determine the effects of these cellular factors
      on the course of infection in older animals, a more neurovirulent SV vector
      (dsNSV) was constructed from a viral strain that causes both prominent spinal
      cord infection with hind-limb paralysis and death in weanling mice. This vector
      has allowed assessment of the effects of BCL-2 and BAX on both mortality and
      paralysis in these hosts. Similar to newborn hosts, weanling mice infected with
      dsNSV encoding BCL-2 or BAX survived better than animals infected with control
      viruses. This finding indicates that BCL-2 and BAX both protect neurons that
      mediate host survival. Neither cellular factor, however, could suppress the
      development of hind-limb paralysis or prevent the degeneration of motor neurons
      in the lumbar spinal cord. Infection of BAX knockout mice with dsNSV demonstrated
      that endogenous BAX also enhances the survival of animals but has no effect on
      paralysis. These findings for the spinal cord are consistent with earlier data
      showing that dying lumbar motor neurons do not exhibit an apoptotic morphology.
      Thus, divergent cell death pathways are activated in different target populations
      of neurons during neurovirulent SV infection of weanling mice.

PMID- 12239317
TI  - Life cycle heterogeneity in animal models of human papillomavirus-associated
      disease.
AB  - Animal papillomaviruses are widely used as models to study papillomavirus
      infection in humans despite differences in genome organization and tissue
      tropism. Here, we have investigated the extent to which animal models of
      papillomavirus infection resemble human disease by comparing the life cycles of
      10 different papillomavirus types. Three phases in the life cycles of all viruses
      were apparent using antibodies that distinguish between early events, the onset
      of viral genome amplification, and the expression of capsid proteins. The
      initiation of these phases follows a highly ordered pattern that appears
      important for the production of virus particles. The viruses examined included
      canine oral papillomavirus, rabbit oral papillomavirus (ROPV), cottontail rabbit
      papillomavirus (CRPV), bovine papillomavirus type 1, and human papillomavirus
      types 1, 2, 11, and 16. Each papillomavirus type showed a distinctive gene
      expression pattern that could be explained in part by differences in tissue
      tropism, transmission route, and persistence. As the timing of life cycle events
      affects the accessibility of viral antigens to the immune system, the ideal model
      system should resemble human mucosal infection if vaccine design is to be
      effective. Of the model systems examined here, only ROPV had a tissue tropism and
      a life cycle organization that resembled those of the human mucosal types. ROPV
      appears most appropriate for studies of the life cycles of mucosal papillomavirus
      types and for the development of prophylactic vaccines. The persistence of
      abortive infections caused by CRPV offers advantages for the development of
      therapeutic vaccines.

PMID- 12239318
TI  - Selective translation of eukaryotic mRNAs: functional molecular analysis of GRSF
      1, a positive regulator of influenza virus protein synthesis.
AB  - To understand the regulation of cap-dependent translation initiation mediated by
      specific 5' untranslated region (UTR) RNA-protein interactions in mammalian
      cells, we have studied the selective translation of influenza virus mRNAs.
      Previous work has shown that the host cell mRNA binding protein guanine-rich
      sequence factor 1 (GRSF-1) bound specifically to conserved viral 5' UTR sequences
      and stimulated translation of viral 5' UTR-driven mRNAs in vitro. In the present
      study, we have characterized the functional domains of GRSF-1 and mapped the RNA
      binding activity of GRSF-1 to RRM 2 (amino acids 194 to 275) with amino-terminal
      deletion glutathione S-transferase (GST)-GRSF-1 proteins. When these mutants were
      assayed for functional activity in vitro, deletion of an Ala-rich region (Delta[2
      94]) appeared to diminish translational stimulation, while deletion of the Ala
      rich region in addition to RRM 1 (Delta[2-194]) resulted in a 4-fold increase in
      translational activation over wild-type GRSF-1 (an overall 20-fold increase in
      activity). We have also mapped the GRSF-1 RNA binding site on influenza virus NP
      and NS1 5' UTRs, which was determined to be the sequence AGGGU. With polysome
      fractionation and cDNA microarray analysis, we have identified cellular and viral
      mRNAs containing putative GRSF-1 binding sites that were transcriptionally up
      regulated and selectively recruited to polyribosomes following influenza virus
      infection. Taken together, these studies demonstrate that RRM 2 is critical for
      GRSF-1 RNA binding and translational activity. Further, our data suggest GRSF-1
      functions by selectively recruiting cellular and viral mRNAs containing 5' UTR
      GRSF-1 binding sites to polyribosomes, which is mediated through interactions
      with cellular proteins.

PMID- 12239319
TI  - Epstein-barr virus-induced changes in B-lymphocyte gene expression.
AB  - To elucidate the mechanisms by which Epstein-Barr virus (EBV) latency III gene
      expression transforms primary B lymphocytes to lymphoblastoid cell lines (LCLs),
      the associated alterations in cell gene expression were assessed by using 4,146
      cellular cDNAs arrayed on nitrocellulose filters and real-time reverse
      transcription-PCR (RT-PCR). A total of 1,405 of the 4,146 cDNAs were detected
      using cDNA probes from poly(A)(+) RNA of IB4 LCLs, a non-EBV-infected Burkitt's
      lymphoma (BL) cell line, BL41, or EBV latency III-converted BL41 cells (BL41EBV).
      Thirty-eight RNAs were consistently twofold more abundant in the IB4 LCL and
      BL41EBV than in BL41 by microarray analysis. Ten of these are known to be EBV
      induced. A total of 23 of 28 newly identified EBV-induced genes were confirmed by
      real-time RT-PCR. In addition, nine newly identified genes and CD10 were EBV
      repressed. These EBV-regulated genes encode proteins involved in signal
      transduction, transcription, protein biosynthesis and degradation, and cell
      motility, shape, or adhesion. Seven of seven newly identified EBV-induced RNAs
      were more abundant in newly established LCLs than in resting B lymphocytes.
      Surveys of eight promoters of newly identified genes implicate NF-kappaB or PU.1
      as potentially important mediators of EBV-induced effects through LMP1 or EBNA2,
      respectively. Thus, examination of the transcriptional effects of EBV infection
      can elucidate the molecular mechanisms by which EBV latency III alters B
      lymphocytes.

PMID- 12239320
TI  - Bronchoalveolar fluid is not a major hindrance to virus-mediated gene therapy in
      cystic fibrosis.
AB  - Successfully targeting the airway epithelium is essential for gene therapy of
      some pulmonary diseases. However, the airway epithelium is resistant to virus
      mediated gene transfer with commonly used vectors. Vectors that interact with
      endogenously expressed receptors on the apical surface significantly increase
      gene transfer efficiency. However, other endogenous components involved in host
      immunity may hinder virus-mediated gene transfer. We tested the effect of
      bronchoalveolar lavage liquid (BAL) from patients with cystic fibrosis (CF), BAL
      from subjects without CF (non-CF BAL), Pseudomonas aeruginosa-derived proteins,
      and an array of inflammatory proteins on gene transfer mediated by adeno
      associated virus type 5 (AAV5) and adenovirus targeted to an apically expressed
      glycosylphosphatidylinositol-modified coxsackie-adenovirus receptor. We found
      that neither CF BAL nor its components had a significant effect on gene transfer
      to human airway epithelium by these vectors. Non-CF BAL significantly impaired
      adenovirus-mediated gene transfer. Removal of immunoglobulins in non-CF BAL
      restored gene transfer efficiency. As virus vectors are improved and mechanisms
      of humoral immunity are elucidated, barriers to successful gene therapy found in
      the complex environment of the human lung can be circumvented.

PMID- 12239321
TI  - Human immunodeficiency virus type 1 nucleocapsid protein nuclear localization
      mediates early viral mRNA expression.
AB  - An important aspect of the pathophysiology of human immunodeficiency virus type 1
      (HIV-1) infection is the ability of the virus to replicate in the host vigorously
      without a latent phase and to kill cells with a dynamic turnover of 1.8 x 10(9)
      cells/day and 10.3 x 10(9) virions/24 h. The transcription of HIV-1 RNA in acute
      infection occurs at two stages; the transcription of viral spliced mRNA occurs
      early, and the transcription of viral genomic RNA occurs later. The HIV-1 Tat
      protein is translated from the early spliced mRNA and is critical for HIV-1
      genomic RNA expression. The cellular transcription factors are important for HIV
      1 early spliced mRNA expression. In this study we show that virion nucleocapsid
      protein (NC) has a role in expression of HIV-1 early spliced mRNA. The HIV-1 NC
      migrates from the cytoplasm to the nucleus and accumulates in the nucleus at 18 h
      postinfection. Mutations on HIV-1 NC zinc fingers change the pattern of early
      viral spliced mRNA expression and result in a delayed expression of early viral
      mRNA in HIV-infected cells. This delayed HIV-1 early spliced mRNA expression
      occurs after proviral DNA has been integrated into the cellular genome, as shown
      by a quantitative integration assay. These results show that virion NC plays an
      important role in inducing HIV-1 early mRNA expression and contributes to the
      rapid viral replication that occurs during HIV-1 infection.

PMID- 12239322
TI  - Influenza virus can enter and infect cells in the absence of clathrin-mediated
      endocytosis.
AB  - Influenza virus has been described to enter host cells via clathrin-mediated
      endocytosis. However, it has also been suggested that other endocytic routes may
      provide additional entry pathways. Here we show that influenza virus may enter
      and infect HeLa cells that are unable to take up ligands by clathrin-mediated
      endocytosis. By overexpressing a dominant-negative form of the Eps15 protein to
      inhibit clathrin-mediated endocytosis, we demonstrate that while transferrin
      uptake and Semliki Forest virus infection were prevented, influenza virus could
      enter and infect cells expressing Eps15Delta95/295. This finding is supported by
      the successful infection of cells with influenza virus in the presence of
      chemical treatments that block endocytosis, namely, chlorpromazine and potassium
      depletion. We show also that influenza virus may infect cells incapable of uptake
      by caveolae. Treatment with the inhibitors nystatin, methyl-beta-cyclodextrin,
      and genistein, as well as transfection of cells with dominant-negative caveolin
      1, had no effect on influenza virus infection. By combining inhibitory methods to
      block both clathrin-mediated endocytosis and uptake by caveolae in the same cell,
      we demonstrate that influenza virus may infect cells by an additional non
      clathrin-dependent, non-caveola-dependent endocytic pathway. We believe this to
      be the first conclusive analysis of virus entry via such a non-clathrin-dependent
      pathway, in addition to the traditional clathrin-dependent route.

PMID- 12239323
TI  - A prenylation inhibitor prevents production of infectious hepatitis delta virus
      particles.
AB  - Hepatitis delta virus (HDV) causes both acute and chronic liver disease
      throughout the world. Effective medical therapy is lacking. Previous work has
      shown that the assembly of HDV virus-like particles (VLPs) could be abolished by
      BZA-5B, a compound with farnesyltransferase inhibitory activity. Here we show
      that FTI-277, another farnesyltransferase inhibitor, prevented the production of
      complete, infectious HDV virions of two different genotypes. Thus, in spite of
      the added complexity and assembly determinants of infectious HDV virions compared
      to VLPs, the former are also sensitive to pharmacological prenylation inhibition.
      Moreover, production of HDV genotype III virions, which is associated with
      particularly severe clinical disease, was as sensitive to prenylation inhibition
      as was that of HDV genotype I virions. Farnesyltransferase inhibitors thus
      represent an attractive potential class of novel antiviral agents for use against
      HDV, including the genotypes associated with most severe disease.

PMID- 12239324
TI  - Rev inhibition strongly affects intracellular distribution of human
      immunodeficiency virus type 1 RNAs.
AB  - To define the human immunodeficiency virus type 1 (HIV-1) RNA maturation
      pathways, we analyzed the intracellular distribution of HIV-1 RNA and the viral
      regulatory proteins Rev and Tat in transfected COS cells and HIV-1-infected
      lymphoid C8166 cells by means of ultrastructural in situ hybridization using
      antisense RNA probes and immunoelectron microscopy. The intranuclear viral RNA
      occurs in ribonucleoprotein fibrils in the perichromatin and interchromatin
      regions. The simultaneous demonstration of Rev, Tat, Br-labeled RNA, and cellular
      proteins SC35 and CRM1 in such fibrils reveals the potential of Rev to associate
      with nascent HIV pre-mRNA and its splicing complex and transport machinery. In a
      rev-minus system, the env intron-containing, incompletely spliced viral RNAs are
      revealed only in the nucleus, indicating that Rev is required to initiate the
      transport to the cytoplasm. Moreover, env intron sequences frequently occur in
      the periphery of interchromatin granule clusters, while the probe containing the
      rev exon sequence does not associate with this nucleoplasmic domain. When cells
      were treated with the CRM1 inhibitor leptomycin B in the presence of Rev protein,
      the env intron containing HIV RNAs formed clusters throughout the nucleoplasm and
      accumulated at the nuclear pores. This suggests that Rev is necessary and
      probably also sufficient for the accumulation of incompletely spliced HIV RNAs at
      the nuclear pores while CRM1 is needed for translocation across the nuclear pore
      complex.

PMID- 12239325
TI  - Mitochondrial targeting and membrane anchoring of a viral replicase in plant and
      yeast cells.
AB  - Replication of the Carnation Italian ringspot virus genomic RNA in plant cells
      occurs in multivesicular bodies which develop from the mitochondrial outer
      membrane during infection. ORF1 in the viral genome encodes a 36-kDa protein,
      while ORF2 codes for the 95-kDa replicase by readthrough of the ORF1 stop codon.
      We have shown previously that the N-terminal part of ORF1 contains the
      information leading to vesiculation of mitochondria and that the 36-kDa protein
      localizes to mitochondria. Using infection, in vivo expression of green
      fluorescent protein fusions in plant and yeast cells, and in vitro mitochondrial
      integration assays, we demonstrate here that both the 36-kDa protein and the
      complete replicase are targeted to mitochondria and anchor to the outer membrane
      with the N terminus and C terminus on the cytosolic side. Analysis of deletion
      mutants indicated that the anchor sequence is likely to correspond approximately
      to amino acids 84 to 196, containing two transmembrane domains. No evidence for a
      matrix-targeting presequence was found, and the data suggest that membrane
      insertion of the viral proteins is mediated by an import receptor-independent
      signal-anchor mechanism relying on the two transmembrane segments and multiple
      recognition signals present in the N-terminal part of ORF1.

PMID- 12239326
TI  - Improved hepatic gene transfer by using an adeno-associated virus serotype 5
      vector.
AB  - Adeno-associated viral (AAV) vectors have been shown to direct stable gene
      transfer and expression in hepatocytes, which makes them attractive tools for
      treatment of inherited disorders such as hemophilia B. While substantial levels
      of coagulation factor IX (F.IX) have been achieved using AAV serotype 2 vectors,
      use of a serotype 5 vector further improves transduction efficiency and levels of
      F.IX transgene expression by 3- to 10-fold. In addition, the AAV-5 vector
      transduces a higher proportion of hepatocytes ( approximately 15%). The
      subpopulations of hepatocytes transduced with either vector widely overlap, with
      the AAV-5 vector transducing additional hepatocytes and showing a wider area of
      transgene expression throughout the liver parenchyma.

PMID- 12239327
TI  - A zebrafish coxsackievirus and adenovirus receptor homologue interacts with
      coxsackie B virus and adenovirus.
AB  - In this study, a zebrafish homologue of the coxsackievirus and adenovirus
      receptor (CAR) protein was identified. Although the extracellular domain of
      zebrafish CAR (zCAR) is less than 50% identical to that of human CAR (hCAR), zCAR
      mediated infection of transfected cells by both adenovirus type 5 and
      coxsackievirus B3. CAR residues interacting deep within the coxsackievirus canyon
      are highly conserved in zCAR and hCAR, which is consistent with the idea that
      receptor contacts within the canyon are responsible for coxsackievirus
      attachment. In contrast, CAR residues contacting the south edge of the canyon are
      not conserved, suggesting that receptor interaction with the viral "puff region"
      is not essential for attachment.

PMID- 12239329
TI  - Specificity and affinity of sialic acid binding by the rhesus rotavirus VP8*
      core.
AB  - Nuclear magnetic resonance spectroscopy demonstrates that the rhesus rotavirus
      hemagglutinin specifically binds alpha-anomeric N-acetylneuraminic acid with a
      K(d) of 1.2 mM. The hemagglutinin requires no additional carbohydrate moieties
      for binding, does not distinguish 3' from 6' sialyllactose, and has approximately
      tenfold lower affinity for N-glycolylneuraminic than for N-acetylneuraminic acid.
      The broad specificity and low affinity of sialic acid binding by the rotavirus
      hemagglutinin are consistent with this interaction mediating initial cell
      attachment prior to the interactions that determine host range and cell type
      specificity.

PMID- 12239328
TI  - Effects of cytotoxic T lymphocytes (CTL) directed against a single simian
      immunodeficiency virus (SIV) Gag CTL epitope on the course of SIVmac239
      infection.
AB  - Vaccine-induced cytotoxic T lymphocytes (CTL) have been implicated in the control
      of virus replication in simian immunodeficiency virus (SIV)-challenged and simian
      human immunodeficiency virus-challenged macaques. Therefore, we wanted to test
      the impact that vaccine-induced CTL responses against an immunodominant Gag
      epitope might have in the absence of other immune responses. By themselves, these
      strong CTL responses failed to control SIVmac239 replication.

PMID- 12239330
TI  - Elevated chemokine responses are maintained in lungs after clearance of viral
      infection.
AB  - We observed two patterns of chemokine expression in the lungs of mice infected
      with murine gammaherpesvirus 68: peaks of chemokine expression correlated with or
      occurred after the peak of viral gene expression. Chemokine expression remained
      elevated through 29 days postinfection.

PMID- 12239331
TI  - Evolutionary dynamics of viral attenuation.
AB  - The genetic trajectory leading to viral attenuation was studied in a canine
      parvovirus (CPV) strain grown on dog kidney cells for 115 transfers. Consensus
      sequences of viral populations at passages 0, 3, 30, 50, 80, and 115 were
      obtained from PCR products covering 86% of the genome; clones from each of the
      80th and 115th passages were also sequenced, covering 69% of the genome. Sixteen
      changes were fixed in the 115th-passage virus sample. Levels of polymorphism were
      strikingly different over time, in part because of a plaque-cloning step at
      passage 112 that reduced variation: passage 80 had 19 variants common among the
      clones, but passage 115 had only a single common variant. Several mutations
      increased in the culture at the same time, with most reaching fixation only after
      the 80th passage. The pattern of evolution was consistent with recombination and
      not with separate selective sweeps of individual mutations. Thirteen of the
      changes observed were identical to or at the same positions as changes observed
      in other isolates of CPV or feline panleukopenia virus.

PMID- 12239332
TI  - Human herpesvirus 8 gene encodes a functional thymidylate synthase.
AB  - We demonstrate that human herpesvirus 8, obtained from the lymphoma cell line BC
      3 as well as from Kaposi's sarcoma lesions, carries a gene that encodes a
      functional thymidylate synthase (TS). The particular characteristics of this
      enzyme are studied and compared to the characteristics of TSs encoded by other
      organisms.

PMID- 12239333
TI  - Inhibition of human immunodeficiency virus type 1 (HIV-1) replication by a two
      amino-acid insertion in HIV-1 Vif from a nonprogressing mother and child.
AB  - We studied a 15-year-old girl, patient X, who has maintained consistently low
      plasma loads of human immunodeficiency virus type 1 (HIV-1) RNA, as well as
      normal and stable CD4(+) T-cell concentrations. She has presented no clinical
      manifestations of AIDS, despite having only received zidovudine monotherapy for a
      part of her life. Patient X's HIV-positive mother (patient Y) has also not
      progressed to AIDS and has never been treated with antiretroviral agents. HIV-1
      isolated from patient X replicated poorly in human peripheral blood mononuclear
      cells (PBMC). In order to map the determinant of the poor growth of patient X's
      isolate, viral sequences from patient X were determined and examined for
      insertion or deletion mutations. These sequences contained a two-amino-acid
      insertion mutation in the Vif gene, which was also observed in uncultured PBMC
      acquired at different times. Furthermore, Vif sequences harbored by patient Y
      contained the identical mutation. These observations suggest that polymorphic HIV
      1 was transmitted to patient X perinatally 15 years previously and has been
      maintained since that time. Recombinant HIV-1, engineered with Vif sequences from
      patient X, replicated in PBMC to levels approximately 20-fold lower than that of
      wild type. Removal of the insertion mutation from this recombinant restored
      replication efficiency to wild-type levels, while introduction of the insertion
      mutation into wild-type Vif sequences resulted in greatly decreased replication.
      Furthermore, Vif protein from patient X's HIV-1 was aberrantly cleaved,
      suggesting a mechanism for loss of Vif function. Since HIV-1 containing these
      sequences replicates poorly, the implication is that the two-amino-acid insertion
      mutation in Vif contributes significantly to the nonprogressor status of this
      mother and child. Further studies of these sequences might provide information
      regarding contributions of Vif structure and/or function to HIV-1 virulence.

PMID- 12239334
TI  - Protective antiviral immune responses to pseudorabies virus induced by DNA
      vaccination using dimethyldioctadecylammonium bromide as an adjuvant.
AB  - To enhance the efficacy of a DNA vaccine against pseudorabies virus (PRV), we
      evaluated the adjuvant properties of plasmids coding for gamma interferon or
      interleukin-12, of CpG immunostimulatory motifs, and of the conventional
      adjuvants dimethyldioctadecylammonium bromide in water (DDA) and sulfolipo
      cyclodextrin in squalene in water. We demonstrate that a DNA vaccine combined
      with DDA, but not with the other adjuvants, induced significantly stronger immune
      responses than plasmid vaccination alone. Moreover, pigs vaccinated in the
      presence of DDA were protected against clinical disease and shed significantly
      less PRV after challenge infection. This is the first study to demonstrate that
      DDA, a conventional adjuvant, enhances DNA vaccine-induced antiviral immunity.

PMID- 12239335
TI  - Insertions in the reverse transcriptase increase both drug resistance and viral
      fitness in a human immunodeficiency virus type 1 isolate harboring the multi
      nucleoside reverse transcriptase inhibitor resistance 69 insertion complex
      mutation.
AB  - Recent studies have shown that the accumulation of multiple mutations associated
      with nucleoside reverse transcriptase inhibitor (NRTI) resistance may be grouped
      as multi-NRTI resistance (MNR) complexes. In this study, we have examined the
      viral fitness of recombinant viruses carrying the reverse transcriptase (RT) of a
      human immunodeficiency virus type 1 (HIV-1) primary isolate harboring mutations
      comprising the MNR 69 insertion complex. Different RT mutants were prepared in
      the sequence context of either the wild-type RT sequence of the HIV-1(BH10)
      isolate or the sequence found in a clinical HIV-1 isolate with the MNR 69
      insertion mutation. As expected, in the presence of zidovudine, recombinant
      viruses harboring the MNR RT from the patient were more fit than wild-type
      viruses. However, in the absence of drug, the virus with the RT from the original
      clinical isolate (SS) was more fit than (i) the wild-type virus with an
      engineered serine insertion between residues 69 and 70 (T69SSS) and (ii) the
      recombinant virus with the MNR RT where the insertion was removed (2S0S). These
      results suggest that RT insertions, in the right sequence context (i.e.,
      additional mutations contained in the MNR 69 insertion complex), enhance NRTI
      resistance and may improve viral fitness. Thus, comparing complex mutation
      patterns with viral fitness may help to elucidate the role of uncharacterized
      drug resistance mutations in antiretroviral treatment failure.

PMID- 12239336
TI  - Identification and expression of immunogenic proteins of a disease-associated
      marine turtle herpesvirus.
AB  - Herpesviruses are associated with several diseases of marine turtles, including
      lung-eye-trachea disease (LETD) and fibropapillomatosis. Two approaches were used
      to identify immunodominant antigens of LETV, the LETD-associated herpesvirus. The
      first approach targeted glycoprotein B, which is known to be immunogenic and
      neutralizing in other species. The second strategy identified LETV proteins
      recognized on Western blots by antibodies in immune green turtle plasma. A 38-kDa
      protein was resolved by two-dimensional gel electrophoresis, sequenced, and
      identified as a scaffolding protein encoded by the overlapping open reading
      frames of UL26 and UL26.5. Glycoprotein B and the scaffolding protein were cloned
      and expressed in Escherichia coli. The expressed proteins were recognized on
      Western blots by antibodies in immune green turtle plasma. Phylogenetic studies
      based on UL26, DNA polymerase, and glycoprotein B revealed that LETV clusters
      with the alphaherpesviruses.

PMID- 12239337
TI  - Inactivation of both the retinoblastoma tumor suppressor and p21 by the human
      papillomavirus type 16 E7 oncoprotein is necessary to inhibit cell cycle arrest
      in human epithelial cells.
AB  - The human papillomavirus (HPV) type 16 E7 oncoprotein must inactivate the
      retinoblastoma tumor suppressor (Rb) pathway to bypass G(1) arrest. However, E7 C
      terminal mutants that were able to inactivate Rb were unable to bypass DNA damage
      induced G(1) arrest and keratinocyte senescence, suggesting that the E7 C
      terminus may target additional G(1) regulators. The E7 C-terminal mutant proteins
      E7 CVQ68-70AAA and E7 Delta79-83 (deletion of positions 79 through 83) were
      further tested in several models of cell cycle arrest associated with elevated
      levels of p21. C-terminal mutations rendered E7 unable to induce S phase and
      endoreduplication in differentiated keratinocytes and rendered it less efficient
      in delaying senescence of human mammary epithelial cells. Interestingly, when
      cell cycle arrest was induced with a peptide form of p21, the E7 C-terminal
      mutants were deficient in overcoming arrest, whereas a mutant defective in Rb
      binding was competent in inhibiting G(1) arrest. These results suggest that the
      inactivation of both p21 and Rb by E7 contributes to subversion of cell cycle
      control in normal human epithelia but that neither p21 nor Rb inactivation alone
      is sufficient.

PMID- 12239338
TI  - Phosphorylation of the porcine reproductive and respiratory syndrome virus
      nucleocapsid protein.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is a cytoplasmic RNA
      virus with the unique or unusual feature of having a nucleocapsid (N) protein
      that is specifically transported to the nucleolus of virus-infected cells. In
      this communication, we show that the N protein is a phosphoprotein. Phosphoamino
      acid analysis of authentic and recombinant N proteins demonstrated that serine
      residues were exclusively phosphorylated. The pattern of phosphorylated N protein
      cellular distribution in comparison with that of [(35)S]methionine-labeled N
      protein suggested that phosphorylation does not influence subcellular
      localization of the protein. Time course studies showed that phosphorylation
      occurred during, or shortly after, synthesis of the N protein and that the
      protein remained stably phosphorylated throughout the life cycle of the virus to
      the extent that phosphorylated N protein was found in the mature virion. Two
      dimensional electrophoresis and acid-urea gel electrophoresis showed that one
      species of the N protein is predominant in virus-infected cells, suggesting that
      multiple phosphorylated isoforms of N do not exist.

PMID- 12239339
TI  - Synergy determination issues.

PMID- 12239340
TI  - Doming modes and dynamics of model heme compounds.
AB  - Synchrotron far-IR spectroscopy and density-functional calculations are used to
      characterize the low-frequency dynamics of model heme FeCO compounds. The
      "doming" vibrational mode in which the iron atom moves out of the porphyrin plane
      while the periphery of this ring moves in the opposite direction determines the
      reactivity of oxygen with this type of molecule in biological systems.
      Calculations of frequencies and absorption intensities and the measured pressure
      dependence of vibrational modes in the model compounds are used to identify the
      doming and related normal modes.

PMID- 12239341
TI  - Structures of bromoalkanes' photodissociation in solution by means of ultrafast
      extended x-ray absorption fine-structure spectroscopy.
AB  - The structures of initial and final products of bromoalkanes' photodisociation
      reaction in cyclohexane solution have been measured with a bond length accuracy
      of 0.02 A by means of ultrafast time-resolved extended x-ray absorption fine
      structure spectroscopy. The photoredaction mechanism is also discussed.

PMID- 12239342
TI  - Physical and functional interactions of histone deacetylase 3 with TFII-I family
      proteins and PIASxbeta.
AB  - TFII-I family proteins are characterized structurally by the presence of multiple
      reiterated I-repeats, each containing a putative helix-loop-helix domain.
      Functionally, they behave as multifunctional transcription factors that are
      activated by a variety of extracellular signals. In studying their subcellular
      localization, we noticed that these transcription factors frequently reside in
      subnuclear domains/dots. Because nuclear dots are believed often to harbor
      components of histone deacetylase enzymes (HDACs), we investigated whether TFII-I
      family proteins colocalize and interact with HDACs. Here, we show that TFII-I and
      its related member hMusTRD1/BEN physically and functionally interact with HDAC3.
      The TFII-I family proteins and HDAC3 also show nearly identical expression
      patterns in early mouse development. Consistent with our earlier observation that
      TFII-I family proteins also interact with PIASxbeta, a member of the E3 ligase
      family involved in the small ubiquitin-like modifier (SUMO) pathway, we show
      further that PIASxbeta physically and functionally interacts with HDAC3 and
      relieves the transcriptional repression exerted by HDAC3 upon TFII-I-mediated
      gene activation. These results suggest a complex interplay between two
      posttranslational pathways-histone modification and SUMOylation-brokered in part
      by TFII-I family proteins.

PMID- 12239344
TI  - Corridors affect plants, animals, and their interactions in fragmented
      landscapes.
AB  - Among the most popular strategies for maintaining populations of both plants and
      animals in fragmented landscapes is to connect isolated patches with thin strips
      of habitat, called corridors. Corridors are thought to increase the exchange of
      individuals between habitat patches, promoting genetic exchange and reducing
      population fluctuations. Empirical studies addressing the effects of corridors
      have either been small in scale or have ignored confounding effects of increased
      habitat area created by the presence of a corridor. These methodological
      difficulties, coupled with a paucity of studies examining the effects of
      corridors on plants and plant-animal interactions, have sparked debate over the
      purported value of corridors in conservation planning. We report results of a
      large-scale experiment that directly address this debate. In eight large-scale
      experimental landscapes that control for patch area and test alternative
      mechanisms of corridor function, we demonstrate that corridors not only increase
      the exchange of animals between patches, but also facilitate two key plant-animal
      interactions: pollination and seed dispersal. Our results show that the
      beneficial effects of corridors extend beyond the area they add, and suggest that
      increased plant and animal movement through corridors will have positive impacts
      on plant populations and community interactions in fragmented landscapes.

PMID- 12239343
TI  - A method for the generation of combinatorial antibody libraries using pIX phage
      display.
AB  - For more than a decade, phage displayed combinatorial antibody libraries have
      been used to generate and select a wide variety of antibodies. We previously
      reported that the phage coat proteins pVII and pIX could be used to display the
      heterodimeric structure of the antibody Fv region. Herein, aspects of this
      technology were invoked and extended to construct a large, human single-chain Fv
      (scFv) library of 4.5 x 10(9) members displayed on pIX of filamentous
      bacteriophage. Furthermore, the diversity, quality, and utility of the library
      were demonstrated by the selection of scFv clones against six different protein
      antigens. Notably, more than 90% of the selected clones showed positive binding
      for their respective antigens after as few as three rounds of panning. Analyzed
      scFvs were also found to be of high affinity. For example, kinetic analysis
      (BIAcore) revealed that scFvs against staphylococcal enterotoxin B and cholera
      toxin B subunit had a nanomolar and subnanomolar dissociation constant,
      respectively, affording affinities comparable to, or exceeding that, of mAbs
      obtained from immunization. High specificity was also attained, not only between
      very distinct proteins, but also in the case of the Ricinus communis ("ricin")
      agglutinins (RCA(60) and RCA(120)), despite >80% sequence homology between the
      two. The results suggested that the performance of pIX-display libraries can
      potentially exceed that of the pIII-display format and make it ideally suited for
      panning a wide variety of target antigens.

PMID- 12239345
TI  - Classification of scale-free networks.
AB  - While the emergence of a power-law degree distribution in complex networks is
      intriguing, the degree exponent is not universal. Here we show that the between
      ness centrality displays a power-law distribution with an exponent eta, which is
      robust, and use it to classify the scale-free networks. We have observed two
      universality classes with eta approximately equal 2.2(1) and 2.0, respectively.
      Real-world networks for the former are the protein-interaction networks, the
      metabolic networks for eukaryotes and bacteria, and the coauthorship network, and
      those for the latter one are the Internet, the World Wide Web, and the metabolic
      networks for Archaea. Distinct features of the mass-distance relation, generic
      topology of geodesics, and resilience under attack of the two classes are
      identified. Various model networks also belong to either of the two classes,
      while their degree exponents are tunable.

PMID- 12239346
TI  - Calpain as an effector of the Gq signaling pathway for inhibition of Wnt/beta 
      catenin-regulated cell proliferation.
AB  - Signaling pathways interact to integrate and regulate information flow in evoking
      complex cellular responses. We have studied the mechanisms and consequences of
      interactions between the Gq and Wnt/beta-catenin pathways. In human colon
      carcinoma SW480 cells, activation of the Gq pathway inhibits beta-catenin
      signaling as determined by transcriptional reporter and cell proliferation
      assays. Ca(2+) release from internal stores results in nuclear export and calpain
      mediated degradation of beta-catenin in the cytoplasm. Galphaq does not inhibit
      the effects of constitutively activated DeltaN-XTCF3-VP16 chimera in SW480 cells.
      Similarly, in HEK293 cells the Gq pathway suppresses beta-catenin-T cell
      factor/lymphocyte enhancer factor-1 transcriptional activity induced by
      Wnt/Frizzled interaction or glycogen synthase kinase-3beta-resistant beta
      catenin, but not DeltaN-XTCF3-VP16. We conclude that Gq signaling promotes
      nuclear export and calpain-mediated degradation of beta-catenin, which therefore
      contributes to the inhibition of Wnt/beta-catenin pathway.

PMID- 12239347
TI  - Chaperone-dependent E3 ubiquitin ligase CHIP mediates a degradative pathway for c
      ErbB2/Neu.
AB  - Overexpression of the transmembrane receptor tyrosine kinase ErbB2 is common in
      multiple malignancies, including breast and ovarian cancer. ErbB2 is resistant to
      degradation mediated by c-Cbl, the E3 ubiquitin ligase responsible for ligand
      induced ubiquitination of ErbB1 (epidermal growth factor receptor). Because of
      its resistance to degradation, ErbB2 is the preferred dimerization partner for
      other members of the ErbB family, and its overexpression in vivo is associated
      with poor prognosis. We now show that the chaperone-binding ubiquitin ligase CHIP
      efficiently ubiquitinates and down-regulates ErbB2. CHIP expression shortens the
      half-life of both nascent and mature ErbB2 protein. In vitro ubiquitination assay
      shows that CHIP serves as a ubiquitin ligase for ErbB2, and both exogenously
      expressed and endogenous CHIP coprecipitate with the kinase. Furthermore, CHIP
      association with ErbB2 requires a chaperone intermediate and is increased by the
      chaperone-binding drug geldanamycin, a potent stimulator of ErbB2 ubiquitination
      and degradation. These data describe a previously unrecognized pathway, amenable
      to pharmacologic manipulation, that mediates ErbB2 stability.

PMID- 12239348
TI  - Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in
      integrin signaling.
AB  - Fibrinogen binding to integrin alphaIIbbeta3 mediates platelet aggregation and
      requires agonist-induced "inside-out" signals that increase alphaIIbbeta3
      affinity. Agonist regulation of alphaIIbbeta3 also takes place in megakaryocytes,
      the bone marrow cells from which platelets are derived. To facilitate mechanistic
      studies of inside-out signaling, we describe here the generation of
      megakaryocytes in quantity from murine embryonic stem (ES) cells. Coculture of ES
      cells for 8-12 days with OP9 stromal cells in the presence of thrombopoietin, IL
      6, and IL-11 resulted in the development of large, polyploid megakaryocytes that
      produced proplatelets. These cells expressed alphaIIbbeta3 and platelet
      glycoprotein Ibalpha but were devoid of hematopoietic stem cell, erythrocyte, and
      leukocyte markers. Mature megakaryocytes, but not megakaryocyte progenitors,
      specifically bound fibrinogen by way of alphaIIbbeta3 in response to platelet
      agonists. Retrovirus-mediated expression of the reporter gene, green fluorescent
      protein, in ES cell-derived megakaryocytes did not affect viability or
      alphaIIbbeta3 function. On the other hand, retroviral expression of CalDAG-GEFI,
      a Rap1 exchange factor identified by megakaryocyte gene profiling as a candidate
      integrin regulator, enhanced agonist-induced activation of Rap1b and fibrinogen
      binding to alphaIIbbeta3 (P < 0.01). These results establish that ES cells are a
      ready source of mature megakaryocytes for integrin studies and other biological
      applications, and they implicate CalDAG-GEFI in inside-out signaling to
      alphaIIbbeta3.

PMID- 12239349
TI  - A self-replicating ligase ribozyme.
AB  - A self-replicating molecule directs the covalent assembly of component molecules
      to form a product that is of identical composition to the parent. When the newly
      formed product also is able to direct the assembly of product molecules, the self
      replicating system can be termed autocatalytic. A self-replicating system was
      developed based on a ribozyme that catalyzes the assembly of additional copies of
      itself through an RNA-catalyzed RNA ligation reaction. The R3C ligase ribozyme
      was redesigned so that it would ligate two substrates to generate an exact copy
      of itself, which then would behave in a similar manner. This self-replicating
      system depends on the catalytic nature of the RNA for the generation of copies. A
      linear dependence was observed between the initial rate of formation of new
      copies and the starting concentration of ribozyme, consistent with exponential
      growth. The autocatalytic rate constant was 0.011 min(-1), whereas the initial
      rate of reaction in the absence of pre-existing ribozyme was only 3.3 x 10(-11)
      M.min(-1). Exponential growth was limited, however, because newly formed ribozyme
      molecules had greater difficulty forming a productive complex with the two
      substrates. Further optimization of the system may lead to the sustained
      exponential growth of ribozymes that undergo self-replication.

PMID- 12239350
TI  - Structure of the inhibitory region of troponin by site directed spin labeling
      electron paramagnetic resonance.
AB  - Site-directed spin labeling EPR (SDSL-EPR) was used to determine the structure of
      the inhibitory region of TnI in the intact cardiac troponin ternary complex.
      Maeda and collaborators have modeled the inhibitory region of TnI (skeletal 96
      112: the structural motif that communicates the Ca(2+) signal to actin) as a
      kinked alpha-helix [Vassylyev, D., Takeda, S., Wakatsuki, S., Maeda, K. & Maeda,
      Y. (1998) Proc. Natl. Acad. Sci. USA 95, 4847-4852), whereas Trewhella and
      collaborators have proposed the same region to be a flexible beta-hairpin [Tung,
      C. S., Wall, M. E., Gallagher, S. C. & Trewhella, J. (2000) Protein Sci. 9, 1312
      1326]. To distinguish between the two models, residues 129-145 of cardiac TnI
      were mutated sequentially to cysteines and labeled with the extrinsic spin probe,
      MTSSL. Sequence-dependent solvent accessibility was measured as a change in power
      saturation of the spin probe in the presence of the relaxation agent. In the
      ternary complex, the 129-137 region followed a pattern characteristic of a
      regular 3.6 residues/turn alpha-helix. The following region, residues 138-145,
      showed no regular pattern in solvent accessibility. Measurements of 4 intradomain
      distances within the inhibitory sequence, using dipolar EPR, were consistent with
      an alpha-helical structure. The difference in side-chain mobility between the
      ternary (C.I.T) and binary (C.I) complexes revealed a region of interaction of
      TnT located at the N-terminal end of the inhibitory sequence, residues 130-135.
      The above findings for the troponin complex in solution do not support either of
      the computational models of the binary complex; however, they are in very good
      agreement with a preliminary report of the x-ray structure of the cardiac ternary
      complex [Takeda, S. Yamashita, A., Maeda, K. & Maeda, Y. (2002) Biophys. J. 82,
      832].

PMID- 12239351
TI  - Autologous transplantation of genetically modified iris pigment epithelial cells:
      a promising concept for the treatment of age-related macular degeneration and
      other disorders of the eye.
AB  - Age-related macular degeneration (ARMD) is the leading cause for visual
      impairment and blindness in the elder population. Laser photocoagulation,
      photodynamic therapy and excision of neovascular membranes have met with limited
      success. Submacular transplantation of autologous iris pigment epithelial (IPE)
      cells has been proposed to replace the damaged retinal pigment epithelium
      following surgical removal of the membranes. We tested our hypothesis that the
      subretinal transplantation of genetically modified autologous IPE cells
      expressing biological therapeutics might be a promising strategy for the
      treatment of ARMD and other retinal disorders. Pigment epithelium-derived factor
      (PEDF) has strong antiangiogenic and neuroprotective activities in the eye.
      Subretinal transplantation of PEDF expressing IPE cells inhibited pathological
      choroidal neovascularization in rat models of laser-induced rupture of Bruch's
      membrane and of oxygen induced ischemic retinopathy. PEDF expressing IPE
      transplants also increased the survival and preserved rhodopsin expression of
      photoreceptor cells in the RCS rat, a model of retinal degeneration. These
      findings suggest a promising concept for the treatment of ARMD and other retinal
      disorders.

PMID- 12239352
TI  - Conditional disruption of synaptic transmission induces male-male courtship
      behavior in Drosophila.
AB  - It is reported here that male-male courtship behavior is evoked instantaneously
      in the fruit fly Drosophila by conditional disruption of synaptic transmission. A
      temperature-sensitive allele of the Drosophila dynamin gene shibire (shi(ts1))
      was expressed by using the GAL4/UAS system to disrupt synaptic transmission from
      GAL4-positive neurons in a temperature-dependent manner. An enhancer-trap GAL4
      line C309 directing shi(ts1) expression in central and peripheral neurons
      (C309/UAS-shi(ts1)) initiated stereotypical precopulatory behavior toward other
      mature males immediately after a temperature shift from the permissive to
      restrictive temperature. At the restrictive temperature, C309/UAS-shi(ts1) males
      formed "courtship chains" and exhibited abnormally high levels of head-to-head
      interactions. The temperature-induced male-male courtship is attributable not to
      an increase in sexual attractiveness but to an increase in sexual activity of
      C309/UAS-shi(ts1) males. Interestingly, the temperature-induced increase in
      sexual activity is specific toward male partners, because C309/UAS-shi(ts1) males
      courted receptive virgin females less vigorously and copulated less efficiently
      after shifted to the restrictive temperature. Among the GAL4-positive neurons in
      C309, conditional disruption of certain cholinergic neurons but not the mushroom
      body intrinsic neurons plays a critical role in the induction of male-male
      courtship. These neurons may be involved in inhibitory systems that normally
      suppress aberrant male-male courtship. The presented strategy that can induce
      behavioral abnormalities by disrupting synaptic transmission in an acute and
      noninvasive manner will allow further exploration as to how distinct neuronal
      groups control sexual orientation and other aspects of reproductive behavior in
      Drosophila.

PMID- 12239353
TI  - The roles of the external, middle, and inner ears in determining the bandwidth of
      hearing.
AB  - The view seems to prevail that the frequency range of hearing is determined by
      the properties of the outer and middle ears. We argue that this view is an
      oversimplification, in part because the reactive component of cochlear input
      impedance, which affects the low-frequency sensitivity of the cochlea, is
      neglected. Further, we use comparisons of audiograms and transfer functions for
      stapes (or columella) velocity or pressure in scala vestibuli near the stapes
      footplate to show that the middle ear by itself is not responsible for limiting
      high-frequency hearing in the few species for which such comparisons are
      possible. Finally, we propose that the tonotopic organization of the cochlea
      plays a crucial role in setting the frequency limits of cochlear sensitivity and
      hence in determining the bandwidth of hearing.

PMID- 12239354
TI  - Identification of Genes Required for the Function of Non-Race-Specific mlo
      Resistance to Powdery Mildew in Barley.
AB  - Recessive alleles (mlo) of the Mlo locus in barley mediate a broad, non-race
      specific resistance reaction to the powdery mildew fungus Erysiphe graminis f sp
      hordei. A mutational approach was used to identify genes that are required for
      the function of mlo. Six susceptible M2 individuals were isolated after
      inoculation with the fungal isolate K1 from chemically mutagenized seed carrying
      the mlo-5 allele. Susceptibility in each of these individuals is due to
      monogenic, recessively inherited mutations in loci unlinked to mlo. The mutants
      identify two unlinked complementation groups, designated Ror1 and Ror2 (required
      for mlo-specified resistance). Both Ror genes are required for the function of
      different tested mlo alleles and for mlo function after challenge with different
      isolates of E. g. f sp hordei. A quantitative cytological time course analysis
      revealed that the host cell penetration efficiency in the mutants is intermediate
      compared with mlo-resistant and Mlo-susceptible genotypes. Ror1 and Ror2 mutants
      could be differentiated from each other by the same criterion. The spontaneous
      formation of cell wall appositions in mlo plants, a subcellular structure
      believed to represent part of the mlo defense, is suppressed in mlo/ror
      genotypes. In contrast, accumulation of major structural components in the
      appositions is seemingly unaltered. We conclude that there is a regulatory
      function for the Ror genes in mlo-specified resistance and propose a model in
      which the Mlo wild-type allele functions as a negative regulator and the Ror
      genes act as positive regulators of a non-race-specific resistance response.

PMID- 12239355
TI  - The Phytochrome-Deficient pcd1 Mutant of Pea Is Unable to Convert Heme to
      Biliverdin IX[alpha].
AB  - We isolated a new pea mutant that was selected on the basis of pale color and
      elongated internodes in a screen under white light. The mutant was designated
      pcd1 for phytochrome chromophore deficient. Light-grown pcd1 plants have yellow
      green foliage with a reduced chlorophyll (Chl) content and an abnormally high Chl
      a/Chl b ratio. Etiolated pcd1 seedlings are developmentally insensitive to far
      red light, show a reduced response to red light, and have no
      spectrophotometrically detectable phytochrome. The phytochrome A apoprotein is
      present at the wild-type level in etiolated pcd1 seedlings but is not depleted by
      red light treatment. Crude phytochrome preparations from etiolated pcd1 tissue
      also lack spectral activity but can be assembled with phycocyanobilin, an analog
      of the endogenous phytochrome chromophore phytochromobilin, to yield a difference
      spectrum characteristic of an apophytochrome-phycocyanobilin adduct. These
      results indicate that the pcd1-conferred phenotype results from a deficiency in
      phytochrome chromophore synthesis. Furthermore, etioplast preparations from pcd1
      seedlings can metabolize biliverdin (BV) IX[alpha] but not heme to
      phytochromobilin, indicating that pcd1 plants are severely impaired in their
      ability to convert heme to BV IX[alpha]. This provides clear evidence that the
      conversion of heme to BV IX[alpha] is an enzymatic process in higher plants and
      that it is required for synthesis of the phytochrome chromophore and hence for
      normal photomorphogenesis.

PMID- 12239356
TI  - Plant-Microbe Interactions: Life and Death at the Interface.

PMID- 12239357
TI  - Cell-to-Cell and Long-Distance Transport of Viruses in Plants.

PMID- 12239358
TI  - Bacterial Pathogens in Plants: Life up against the Wall.

PMID- 12239359
TI  - Fungal Infection of Plants.

PMID- 12239360
TI  - Genetics and Utilization of Pathogen Resistance in Plants.

PMID- 12239361
TI  - Plant Disease Resistance Genes: Function Meets Structure.

PMID- 12239362
TI  - Death Don't Have No Mercy: Cell Death Programs in Plant-Microbe Interactions.

PMID- 12239363
TI  - Systemic Acquired Resistance.

PMID- 12239364
TI  - Preformed Antimicrobial Compounds and Plant Defense against Fungal Attack.

PMID- 12239365
TI  - Mechanisms of Pathogen-Derived Resistance to Viruses in Transgenic Plants.

PMID- 12239366
TI  - Using Hypoviruses to Probe and Perturb Signal Transduction Processes Underlying
      Fungal Pathogenesis.

PMID- 12239367
TI  - Biocontrol of Soilborne Plant Pathogens.

PMID- 12239368
TI  - Plant Cell Responses to Arbuscular Mycorrhizal Fungi: Getting to the Roots of the
      Symbiosis.

PMID- 12239369
TI  - Rhizobial and Actinorhizal Symbioses: What Are the Shared Features?

PMID- 12239370
TI  - Localized Apical Increases of Cytosolic Free Calcium Control Pollen Tube
      Orientation.
AB  - To reach the ovule, pollen tubes must undergo many changes in growth direction.
      We have shown in previous work that elevation of cytosolic free calcium ([Ca2+]c)
      can manipulate orientation in growing pollen tubes, but our results suggested
      that [Ca2+]c changes either in the tip or in more distal regions might regulate
      the critical orienting mechanism. To identify the spatial location of the
      orienting motor, we combined the techniques of ion imaging with confocal
      microscopy and localized photoactivation of loaded caged Ca2+ (nitr-5) and diazo
      2 (a caged Ca2+ chelator) to manipulate [Ca2+]c in different pollen tube domains.
      We found that increasing [Ca2+]c on one side of the pollen tube apex induced
      reorientation of the growth axis toward that side. Similarly, a decrease in
      [Ca2+]c promoted bending toward the opposite side. These effects could be
      mimicked by imposing localized external gradients of an ionophore (A23187) or a
      Ca2+ channel blocker (GdCl3); the pollen tubes bend toward the highest
      concentration of A23187 and away from GdCl3. Manipulation of [Ca2+]c in regions
      farther back from the apical zone also induced changes in growth direction, but
      the new orientation was at random. We observed communication of these distal
      events to the tip through a slow-moving [Ca2+]c wave. These data show that
      localized changes of [Ca2+]c in the tip, which could result from asymmetric
      channel activity, control the direction of pollen tube growth.

PMID- 12239371
TI  - Cell-Specific Expression of Mitochondrial Transcripts in Maize Seedlings.
AB  - Although mitochondria are thought to assume crucial and possibly novel
      physiological functions during male gametogenesis, it is not known to what extent
      mitochondrial function is necessary for other aspects of plant development or to
      what degree the expression of plant mitochondrial genes is subject to cell
      specific regulation, particularly during vegetative growth. We have used in situ
      hybridization to show that extensive differences exist in the levels of
      mitochondrial RNAs (mtRNAs) among different tissues and among different
      individual cell types within the same organ of maize seedlings. The expression of
      all examined mtRNAs is enhanced in vascular bundles, particularly in procambium-
      and xylem-forming cells. Mitochondrial transcript levels correlated highly with
      cell division activity. For example, in roots, the transcripts are abundant in
      the dividing cells of the meristem but drop to very low levels in the nondividing
      cells of the root cap and the meristem quiescent center. By comparison, levels of
      functional mitochondria, as assessed by rhodamine-123 fluorescence, did not vary
      greatly among the same group of cells. In shoots, in situ hybridization and blot
      hybridization revealed differences in the patterns of localization among
      different mtRNAs. The results indicate that during vegetative growth,
      mitochondrial gene expression at the transcript level is subject to an unexpected
      degree of cell-specific regulation and that different controls may operate on
      different trancripts.

PMID- 12239372
TI  - Inhibition of Programmed Cell Death in Tobacco Plants during a Pathogen-Induced
      Hypersensitive Response at Low Oxygen Pressure.
AB  - The hypersensitive response (HR) of plants to invading pathogens is thought to
      involve a coordinated activation of plant defense mechanisms and programmed cell
      death (pcd). To date, little is known about the mechanism underlying death of
      plant cells during this response. In addition, it is not known whether
      suppression of pcd affects the induction of other defense mechanisms during the
      HR. Here, we report that death of tobacco cells (genotype NN) infected with
      tobacco mosaic virus (TMV) is inhibited at low oxygen pressure. In contrast,
      virus replication and activation of defense mechanisms, as measured by synthesis
      of the pathogenesis-related protein PR-1a, were not inhibited at low oxygen
      pressure. Bacterium-induced pcd was also inhibited at low oxygen pressure.
      However, pcd induced by TMV or bacteria was not inhibited in transgenic tobacco
      plants expressing the mammalian anti-pcd protein Bcl-XL. Our results suggest that
      ambient oxygen levels are required for efficient pcd induction during the HR of
      plants and that activation of defense responses can be uncoupled from cell death.
      Furthermore, pcd that occurs during the interaction of tobacco with TMV or
      bacteria may be distinct from some cases of pcd or apoptosis in animals that are
      insensitive to low oxygen or inhibited by the Bcl-XL protein.

PMID- 12239373
TI  - EF-1[alpha] Is Associated with a Cytoskeletal Network Surrounding Protein Bodies
      in Maize Endosperm Cells.
AB  - By using indirect immunofluorescence and confocal microscopy, we documented
      changes in the distribution of elongation factor-1[alpha] (EF-1[alpha]), actin,
      and microtubules during the development of maize endosperm cells. In older
      interphase cells actively forming starch grains and protein bodies, the protein
      bodies are enmeshed in EF-1[alpha] and actin and are found juxtaposed with a
      multidirectional array of microtubules. Actin and EF-1[alpha] appear to exist in
      a complex, because we observed that the two are colocalized, and treatment with
      cytochalasin D resulted in the redistribution of EF-1[alpa]. These data suggest
      that EF-1[alpha] and actin are associated in maize endosperm cells and may help
      to explain the basis of the correlation we found between the concentration of EF
      1[alpha] and lysine content. The data also support the hypothesis that the
      cytoskeleton plays a role in storage protein deposition. The distributions of EF
      1[alpha] actin, and microtubules change during development. We observed that in
      young cells before the accumulation of starch and storage protein, EF-1[alpha],
      actin, and microtubules are found mainly in the cell cortex or in association
      with nuclei.

PMID- 12239374
TI  - Spatial Organization of Calcium Signaling Involved in Cell Volume Control in the
      Fucus Rhizoid.
AB  - Subprotoplasts prepared from different regions of rhizoid and thallus cells of
      Fucus zygotes displayed mechanosensitive plasma membrane channels in cell
      attached patch-clamp experiments by using laser microsurgery. In excised patches,
      this channel was found to be voltage gated, carrying K+ outward and Ca2+ inward,
      with a relative permeability of Ca2+/K+ of 0.35 to 0.5, and an increased open
      probability at membrane potentials more positive than -80 mV. No significant
      difference was found in the density of this channel type from different regions
      of rhizoid or thallus cells. Hypoosmotic treatment of intact zygotes induced
      dramatic transient elevations of cytoplasmic Ca2+, initiating at the rhizoid apex
      and propagating in a wavelike manner to subapical regions. Localized initiation
      of the Ca2+ transient correlated with greater osmotic swelling at the rhizoid
      apex compared with other regions of the zygote. Ca2+ transients exhibited a
      refractory period between successive hypoosmotic shocks, during which additional
      transients could not be elicited and the ability to osmoregulate was impaired.
      Buffering the Ca2+ transients with microinjected Br2BAPTA similarly reduced the
      ability of rhizoid cells to osmoregulate. Ca2+ influx was associated with the
      initiation of the Ca2+ transient in apical regions, whereas intracellular sources
      contributed to its propagation. Thus, localized signal transduction is patterned
      by interactions of the cell wall, plasma membrane, and intracellular Ca2+ stores.

PMID- 12239375
TI  - Isolation of a 90-kD Microtubule-Associated Protein from Tobacco Membranes.
AB  - The organization and function of microtubules in plant cells are important in key
      developmental events, including the regulation of directional cellulose
      deposition. Bridges connecting microtubules to each other and to membranes and
      other organelles have been documented by electron microscopy; however, the
      biochemical and molecular nature of these linkages is not known. We have
      partitioned proteins from a suspension culture of tobacco into cytosolic and
      membrane fractions, solubilized the membrane fraction with a zwitterionic
      detergent, and then used affinity chromatography and salt elution to isolate
      tubulin binding proteins. Dark-field microscopy of in vitro-assembled
      microtubules showed that the eluted proteins from both fractions induce
      microtubule bundling and, in the presence of purified tubulin, promote
      microtubule elongation. Gel electrophoresis of the eluted proteins revealed two
      distinct sets of polypeptides. Those in the membrane eluate included unique bands
      with apparent molecular masses of 98, 90, and 75 kD in addition to bands present
      in both eluates. The cytosolic eluate, in contrast, typically included relatively
      smaller proteins. The eluted proteins also bound to taxol-stabilized
      microtubules. Initial immunological characterization using monoclonal antibodies
      raised against the 90-kD polypeptide showed that it is colocalized in situ with
      cortical microtubules in tobacco protoplast ghosts.

PMID- 12239376
TI  - Signal Transduction in Barley Aleurone Protoplasts Is Calcium Dependent and
      Independent.
AB  - Gibberellic acid (GA) increases Ca2+ and calmodulin (CaM) levels in barley
      aleurone cells, and abscisic acid (ABA) antagonizes the GA effect. These
      alterations in cytoplasmic Ca2+ and CaM have been suggested to be central
      regulators of the secretory response of the barley aleurone. Using microinjection
      of caged Ca2+, Ca2+ chelators, and CaM, we mimicked or blocked these hormonally
      induced changes in Ca2+ and CaM and assessed their effects on GA and ABA action.
      Although mimicking GA-induced changes in Ca2+ and CaM did not mimic GA action,
      blocking these changes did prevent GA stimulation of secretion. The induction of
      the amylase gene by GA was, however, unaffected. Similarly, blocking the decrease
      in Ca2+ normally caused by ABA in these cells blocked ABA action, except that
      induction of Em gene transcription by ABA was unaffected. These results suggest
      that GA and ABA signals are transduced by Ca2+- and CaM-dependent and Ca2+- and
      CaM-independent systems in the aleurone cell.

PMID- 12239377
TI  - Gibberellic Acid Induces Vacuolar Acidification in Barley Aleurone.
AB  - The roles of gibberellic acid (GA3) and abscisic acid (ABA) in the regulation of
      vacuolar pH (pHv) in aleurone cells of barley were investigated using the pH
      sensitive fluorescent dye 2[prime],7[prime]-bis(2-carboxyethyl)-5(6)
      carboxyfluorescein (BCECF). BCECF accumulated in vacuoles of aleurone cells, but
      sequestration of the dye did not affect its sensitivity to pH. BCECF-loaded
      aleurone cells retained their ability to respond to both GA3 and ABA. The pHv of
      freshly isolated aleurone cells is 6.6, but after incubation in GA3, the pHv fell
      to 5.8. The pHv of cells not incubated in hormones or in the presence of ABA
      showed little or no acidification. The aleurone tonoplast contains both vacuolar
      ATPase and vacuolar pyrophosphatase, but the levels of pump proteins were not
      affected by incubation in the presence or absence of hormones. We conclude that
      GA3 affects the pHv in aleurone cells by altering the activities of tonoplast H+
      pumps but not the amounts of pump proteins.

PMID- 12239378
TI  - RNA-Mediated Virus Resistance: Role of Repeated Transgenes and Delineation of
      Targeted Regions.
AB  - Resistance to cowpea mosaic virus (CPMV) in transgenic Nicotiana benthamiana
      plants is RNA mediated. In resistant CPMV movement protein (MP) gene-transformed
      lines, transgene steady state mRNA levels were low, whereas nuclear transcription
      rates were high, implying that a post-transcriptional gene-silencing mechanism is
      at the base of the resistance. The silencing mechanism can also affect potato
      virus X (PVX) RNAs when they contain CPMV MP gene sequences. In particular,
      sequences situated in the 3[prime] part of the transcribed region of the MP
      transgene direct elimination of recombinant PVX genomes. Remarkably, successive
      portions of this 3[prime] part, which can be as small as 60 nucleotides, all tag
      PVX genomes for degradation. These observations suggest that the entire 3[prime]
      part of the MP transgene mRNA is the initial target of the silencing mechanism.
      The arrangement of transgenes in the plant genome plays an important role in
      establishing resistance because the frequency of resistant lines increased from
      20 to 60% when transformed with a transgene containing a direct repeat of MP
      sequences rather than a single MP transgene. Interestingly, we detected strong
      methylation in all of the plants containing directly repeated MP sequences. In
      sensitive lines, only the promoter region was found to be heavily methylated,
      whereas in resistant lines, only the transcribed region was strongly methylated.

PMID- 12239379
TI  - cGMP Is Required for Gibberellic Acid-Induced Gene Expression in Barley Aleurone.
AB  - The occurrence and roles of cGMP were investigated in aleurone layers and
      protoplasts isolated from barley (cv Himalaya) grain. Levels of cGMP in freshly
      isolated barley aleurone layers ranged from 0.065 to 0.08 pmol/g fresh weight of
      tissue, and cGMP levels increased transiently after incubation in gibberellic
      acid (GA). Abscisic acid (ABA) did not increase cGMP levels in aleurone layers.
      LY 83583 (LY), an inhibitor of guanylyl cyclase, prevented the GA-induced
      increase in cGMP and inhibited GA-induced [alpha]-amylase synthesis and
      secretion. The inhibitory effects of LY could be overcome by membrane-permeant
      analogs of cGMP. LY also prevented GA-induced accumulation of [alpha]-amylase and
      GAMYB mRNAs. cGMP alone was not sufficient to induce the accumulation of [alpha]
      amylase or GAMYB mRNA. LY had a less dramatic effect on the accumulation of mRNAs
      encoding the ABA-responsive gene Rab21. We conclude that cGMP plays an important
      role in GA, but not ABA, signaling in the barley aleurone cell.

PMID- 12239380
TI  - An Abscisic Acid-Activated and Calcium-Independent Protein Kinase from Guard
      Cells of Fava Bean.
AB  - Abscisic acid (ABA) regulation of stomatal aperture is known to involve both Ca2+
      dependent and Ca2+-independent signal transduction pathways. Electrophysiological
      studies suggest that protein phosphorylation is involved in ABA action in guard
      cells. Using biochemical approaches, we identified an ABA-activated and Ca2+-
      independent protein kinase (AAPK) from guard cell protoplasts of fava bean.
      Autophosphorylation of AAPK was rapidly (~1 min) activated by ABA in a Ca2+-
      independent manner. ABA-activated autophosphorylation of AAPK occurred on serine
      but not on tyrosine residues and appeared to be guard cell specific. AAPK
      phosphorylated histone type III-S on serine and threonine residues, and its
      activity toward histone type III-S was markedly stimulated in ABA-treated guard
      cell protoplasts. Our results suggest that AAPK may play an important role in the
      Ca2+-independent ABA signaling pathways of guard cells.

PMID- 12239381
TI  - Suppression of Virus Accumulation in Transgenic Plants Exhibiting Silencing of
      Nuclear Genes.
AB  - Homology-dependent gene silencing contributes to variation between transgenic
      plants with respect to transgene and/or endogenous gene expression levels. Recent
      studies have linked post-transcriptional gene silencing and virus resistance in
      plants expressing virus-derived transgenes. Using a potato virus X vector, we
      present three examples in which silencing of nonviral transgenes prevented virus
      accumulation. This effect was dependent on sequence homology between the virus
      and the silenced transgene. Analysis of potato virus X derivatives carrying
      bacterial [beta]-glucuronidase (GUS) sequences showed that the 3[prime] region of
      the GUS coding sequence was a target of the silencing mechanism in two
      independent tobacco lines. Methylation of the silenced GUS transgenes in these
      lines was also concentrated in the 3[prime] region of the GUS coding sequence.
      Based on this concurrence, we propose a link between the DNA-based transgene
      methylation and the RNA-based gene silencing process.

PMID- 12239382
TI  - Localization of Actin mRNA during the Establishment of Cell Polarity and Early
      Cell Divisions in Fucus Embryos.
AB  - Localization of mRNA is a well-described mechanism to account for the asymmetric
      distribution of proteins in polarized somatic cells and embryos of animals. In
      zygotes of the brown alga Fucus, F-actin is localized at the site of polar growth
      and accumulates at the cell plates of the first two divisions of the embryo. We
      used a nonradioactive, whole-mount in situ hybridization protocol to show the
      pattern of actin mRNA localization. Until the first cell division, the pattern of
      actin mRNA localization is identical to that of total poly(A)+ RNA, that is, a
      symmetrical distribution in the zygote followed by an actin-dependent
      accumulation at the thallus pole at the time of polar axis fixation. At the end
      of the first division, actin mRNA specifically is redistributed from the thallus
      pole to the cell plates of the first two divisions in the rhizoid. This specific
      pattern of localization in the zygote and embryo involves the redistribution of
      previously synthesized actin mRNA. The initial asymmetry of actin mRNA at the
      thallus pole of the zygote requires polar axis fixation and microfilaments but
      not microtubules, cell division, or polar growth. However, redistribution of
      actin mRNA from the thallus pole to the first cell plate is insensitive to
      cytoskeletal inhibitors but is dependent on cell plate formation. The F-actin
      that accumulates at the rhizoid tip is not accompanied by the localization of
      actin mRNA. However, maintenance of an accumulation of actin protein at the cell
      plates of the rhizoid could be explained, at least partially, by a mechanism
      involving localization of actin mRNA at these sites. The pattern and requirements
      for actin mRNA localization in the Fucus embryo may be relevant to polarization
      of the embryo and asymmetric cell divisions in higher plants as well as in other
      tip-growing plant cells.

PMID- 12239383
TI  - Production of Salicylic Acid Precursors Is a Major Function of Phenylalanine
      Ammonia-Lyase in the Resistance of Arabidopsis to Peronospora parasitica.
AB  - Arabidopsis ecotype Columbia (Col-0) seedlings, transformed with a phenylalanine
      ammonia-lyase 1 promoter (PAL1)-[beta]-glucuronidase (GUS) reporter construct,
      were inoculated with virulent and avirulent isolates of Peronospora parasitica.
      The PAL1 promoter was constitutively active in the light in vascular tissue but
      was induced only in the vicinity of fungal structures in the incompatible
      interaction. A double-staining procedure was developed to distinguish between GUS
      activity and fungal structures. The PAL1 promoter was activated in cells
      undergoing lignification in the incompatible interaction in response to the
      pathogen. Pretreatment of the seedlings with 2-aminoindan-2-phosphonic acid
      (AIP), a highly specific PAL inhibitor, made the plants completely susceptible.
      Lignification was suppressed after AIP treatment, and surprisingly, pathogen
      induced PAL1 promoter activity could not be detected. Treatment of the seedlings
      with 2-hydroxyphenylaminosulphinyl acetic acid (1,1-dimethyl ester) (OH-PAS), a
      cinnamyl alcohol dehydrogenase inhibitor specific for the lignification pathway,
      also caused a shift toward susceptibility, but the effect was not as pronounced
      as it was with AIP. Significantly, although OH-PAS suppressed pathogen-induced
      lignification, it did not suppress pathogen-induced PAL1 promoter activation.
      Salicylic acid (SA), supplied to AIP-treated plants, restored resistance and both
      pathogen-induced lignification and activation of the PAL1 promoter. Endogenous SA
      levels increased significantly in the incompatible but not in the compatible
      combination, and this increase was suppressed by AIP but not by OH-PAS. These
      results provide evidence of the central role of SA in genetically determined
      plant disease resistance and show that lignification per se, although providing a
      component of the resistance mechanism, is not the deciding factor between
      resistance and susceptibility.

PMID- 12239384
TI  - Interference between Two Specific Pathogen Recognition Events Mediated by
      Distinct Plant Disease Resistance Genes.
AB  - We demonstrate that the interaction of the avirulence gene avrRpt2 and the
      cognate resistance gene RPS2 interferes with the interaction of avrRpm1-RPM1 in
      Arabidopsis. Interference is mediated outside of the bacterial pathogen
      Pseudomonas syringae, presumably at the level of recognition of avr-dependent
      signals, yet does not require the wild-type RPS2 product. A numerical excess of
      P. syringae expressing avrRpm1 can overcome this interference in mixed
      inoculations. The interference of avrRpt2-RPS2 engagement with RPM1-dependent
      functions is mirrored by transcriptional activation of genes preferentially
      expressed during RPM1- or RPS2-mediated disease resistance reactions. This
      demonstration of interference between two plant disease resistance genes suggests
      that their products compete for a common element(s) in a signal transduction
      pathway leading to disease resistance.

PMID- 12239385
TI  - Localization of a Rho GTPase Implies a Role in Tip Growth and Movement of the
      Generative Cell in Pollen Tubes.
AB  - The Rho family GTPases function as key molecular switches, controlling a variety
      of actin-dependent cellular processes, such as the establishment of cell
      polarity, cell morphogenesis, and movement in diverse eukaryotic organisms. A
      novel subfamily of Rho GTPases, Rop, has been identified in plants. Protein gel
      blot and RNA gel blot hybridization analyses indicated that one of these plant
      Rho GTPases, Rop1, is expressed predominantly in the male gametophyte (pollen and
      pollen tubes). Cell fractionation analysis of pollen tubes showed that Rop is
      partitioned into soluble and particulate fractions. The particulate Rop could be
      solubilized with detergents but not with salts, indicating that it is tightly
      bound to membranes. The membrane association appears to result from membrane
      anchoring via a geranylgeranyl group because an in vitro isoprenylation assay
      demonstrated that Rop1Ps is geranylgeranylated. Subcellular localization, using
      indirect immunofluorescence and confocal microscopy, showed that Rop is highly
      concentrated in the cortical region of the tube apex and in the periphery of the
      generative cell. The cortical Rop protein at the apex forms a gradient with
      decreasing concentration from tip to base and appears to be associated with the
      plasma membrane. These results suggest that the apical Rop GTPase may be involved
      in the signaling mechanism that controls the actin-dependent tip growth of pollen
      tubes. Localization of the Rop GTPase to the periphery of the generative cell is
      analogous to that of myosin, suggesting that the Rop GTPase plays an important
      role in the modulation of an actomyosin motor system involved in the movement of
      the generative cell.

PMID- 12239386
TI  - kurkku, a Phenotype of Acetabularia acetabulum That Is Arrested in Vegetative
      Growth, Can Be Rescued with Wild-Type Cytoplasm.
AB  - We isolated several spontaneous phenotypes in the giant unicell Acetabularia
      acetabulum that have vegetative terminal morphologies. Because they arrest in
      vegetative development, these cell lines are effectively immortalized. However,
      they had to be rescued before they could be studied via classical genetics
      because no heterozygotes from the original self-crosses were found, that is, the
      wild-type siblings yielded only wild-type progeny. We attempted to rescue these
      phenotypes in three ways: by amputating the cell apex, by "piggybacking" the
      mutant nucleus through development in a binucleate heterokaryon, and by replacing
      the abnormal apex with a wild-type apex. We used one of our immortal cell lines,
      kurkku, which has a terminal phenotype consistent with arrest early in the
      juvenile phase of vegetative development, as a prototype for these rescue
      methods. The kurkku phenotype segregated 1:3 in the original self-cross in which
      it arose as if it were a single, recessive Mendelian trait. Although amputation
      failed to rescue kurkku, we succeeded in compensating for the defect both in
      binucleate heterokaryons and in apical grafts to wild-type cells. kurkku was
      always recovered in the progeny of the self-crosses of these grafts. These unique
      ways of analyzing vegetative mutants, combined with the ability to then perform
      classical genetics, may make A. acetabulum a powerful unicellular model system
      for the study of vegetative phase change in plants.

PMID- 12239387
TI  - Apoptosis: A Functional Paradigm for Programmed Plant Cell Death Induced by a
      Host-Selective Phytotoxin and Invoked during Development.
AB  - The host-selective AAL toxins secreted by Alternaria alternata f sp lycopersici
      are primary chemical determinants in the Alternaria stem canker disease of
      tomato. The AAL toxins are members of a new class of sphinganine analog
      mycotoxins that cause cell death in both animals and plants. Here, we report
      detection of stereotypic hallmarks of apoptosis during cell death induced by
      these toxins in tomato. DNA ladders were observed during cell death in toxin
      treated tomato protoplasts and leaflets. The intensity of the DNA ladders was
      enhanced by Ca2+ and inhibited by Zn2+. The progressive delineation of fragmented
      DNA into distinct bodies, coincident with the appearance of DNA ladders, also was
      observed during death of toxin-treated tomato protoplasts. In situ analysis of
      cells dying during development in both onion root caps and tomato leaf tracheary
      elements revealed DNA fragmentation localized to the dying cells as well as the
      additional formation of apoptotic-like bodies in sloughing root cap cells. We
      conclude that the fundamental elements of apoptosis, as characterized in animals,
      are conserved in plants. The apoptotic process may be expressed during some
      developmental transitions and is the functional process by which symptomatic
      lesions are formed in the Alternaria stem canker disease of tomato. Sphinganine
      analog mycotoxins may be used to characterize further signaling pathways leading
      to apoptosis in plants.

PMID- 12239388
TI  - Cleavage of Nuclear DNA into Oligonucleosomal Fragments during Cell Death Induced
      by Fungal Infection or by Abiotic Treatments.
AB  - It is often claimed that programmed cell death (pcd) exists in plants and that a
      form of pcd known as the hypersensitive response is triggered as a defense
      mechanism by microbial pathogens. However, in contrast to animals, no feature in
      plants universally identifies or defines pcd. We have looked for a hallmark of
      pcd in animal cells, namely, DNA cleavage, in plant cells killed by infection
      with incompatible fungi or by abiotic means. We found that cell death triggered
      in intact leaves of two resistant cowpea cultivars by the cowpea rust fungus is
      accompanied by the cleavage of nuclear DNA into oligonucleosomal fragments (DNA
      laddering). Terminal deoxynucleotidyl transferase-mediated dUTP nick end in situ
      labeling of leaf sections showed that fungus-induced DNA cleavage occurred only
      in haustorium-containing cells and was detectable early in the degeneration
      process. Such cytologically detectable DNA cleavage was also observed in vascular
      tissue of infected and uninfected plants, but no DNA laddering was detected in
      the latter. DNA laddering was triggered by [greater than or equal to]100 mM KCN,
      regardless of cowpea cultivar, but not by physical cell disruption or by
      concentrations of H2O2, NaN3, CuSO4, or ZnCl2 that killed cowpea cells at a rate
      similar to that of ladder-inducing KCN concentrations. These and other results
      suggest that the hypersensitive response to microbial pathogens may involve a pcd
      with some of the characteristics of animal apoptosis and that DNA cleavage is a
      potential indicator of pcd in plants.

PMID- 12239389
TI  - The Critical Requirement for Linolenic Acid Is Pollen Development, Not
      Photosynthesis, in an Arabidopsis Mutant.
AB  - The very high proportions of trienoic fatty acids found in chloroplast membranes
      of all higher plants suggest that these lipid structures might be essential for
      photosynthesis. We report here on the production of Arabidopsis triple mutants
      that contain negligible levels of trienoic fatty acids. Photosynthesis at
      22[deg]C was barely affected, and vegetative growth of the mutants was identical
      with that of the wild type, demonstrating that any requirement for trienoic acyl
      groups in membrane structure and function is relatively subtle. Although
      vegetative growth and development were unaffected, the triple mutants are male
      sterlle and produce no seed under normal conditions. Comparisons of pollen
      development in wild-type and triple mutant flowers established that pollen grains
      in the mutant developed to the tricellular stage. Exogenous applications of
      [alpha]-llnolenate or jasmonate restored fertility. Taken together, the results
      demonstrate that the critical role of trienoic acids in the life cycle of plants
      is as the precursor of oxylipin, a signaling compound that regulates final
      maturation processes and the release of pollen.

PMID- 12239390
TI  - Size and Structure of Replicating Mitochondrial DNA in Cultured Tobacco Cells.
AB  - The BY-2 tobacco cell line was used to study the size and structure of
      replicating mitochondrial DNA (mtDNA). Approximately 70 to 90% of the newly
      synthesized mtDNA did not migrate during pulsed-field gel electrophoresis. Moving
      pictures of the fluorescently labeled molecules showed that most of the immobile
      well-bound DNA was in structures larger than the size of the BY-2 mitochondrial
      genome of ~270 kb. Most of the structures appeared as complex forms with multiple
      DNA fibers. The sizes of the circular molecules that were also observed ranged
      continuously from ~20 to 560 kb without prominent size classes. Pulse-chase and
      mung bean nuclease experiments showed that the well-bound DNA contained single
      stranded regions and was converted to linear molecules of between 50 and 150 kb.
      MtDNA replication in plants may be initiated by recombination events that create
      branched structures of multigenomic concatemers that are then processed to 50- to
      150-kb subgenomic fragments.

PMID- 12239391
TI  - Oligogalacturonides Prevent Rhizogenesis in rolB-Transformed Tobacco Explants by
      Inhibiting Auxin-Induced Expression of the rolB Gene.
AB  - Oligogalacturonides elicit several defense responses and regulate different
      aspects of growth and development in plants. Many of the development-related
      effects of oligogalacturonides appear to be amenable to an auxin antagonist
      activity of these oligosaccharins. To clarify the role of oligogalacturonides in
      antagonizing auxin, we analyzed their effect on root formation in leaf explants
      of tobacco harboring the plant oncogene rolB. We show here that
      oligogalacturonides are capable of inhibiting root morphogenesis driven by rolB
      in transgenic leaf explants when this process requires exogenous auxin. Because
      rolB expression is induced by auxin and dramatically alters the response to this
      hormone in transformed plant cells, the inhibiting effect of oligogalacturonides
      could be exerted on the induction of rolB and/or at some other auxin-requiring
      step(s) in rhizogenesis. We show that oligogalacturonides antagonize auxin
      primarily because they strongly inhibit auxin-regulated transcriptional
      activation of a rolB-[beta]-glucuronidase gene fusion in both leaf explants and
      cultured leaf protoplasts. In contrast, oligogalacturonides do not inhibit
      rhizogenesis when rolB transcriptional activation is made independent of auxin,
      as shown by the lack of inhibition of root formation in leaf explants containing
      rolB driven by a tetracycline-inducible promoter.

PMID- 12239392
TI  - Regulation of Plant Defense Response to Fungal Pathogens: Two Types of Protein
      Kinases in the Reversible Phosphorylation of the Host Plasma Membrane H+-ATPase.
AB  - The role of reversible phosphorylation of the host plasma membrane H+-ATPase in
      signal transduction during the incompatible interaction between tomato cells and
      the fungal pathogen Cladosporium fulvum was investigated. Tomato cells (with the
      Cf-5 resistance gene) or isolated plasma membranes from Cf-5 cells treated with
      elicitor preparations from race 2.3 or 4 of C. fulvum (containing the avr5 gene
      product) showed a marked dephosphorylation of plasma membrane H+-ATPase. Similar
      treatment with elicitor preparations from races 5 and 2.4.5.9.11 (lacking the
      avr5 gene product) showed no change in dephosphorylation. Elicitor (race 4)
      treatment of cells, but not of isolated plasma membranes, for 2 hr resulted in
      rephosphorylation of the ATPase via Ca2+-dependent protein kinases. The initial
      (first hour) rephosphorylation was enhanced by protein kinase C (PKC) activators
      and was prevented by PKC inhibitors. Activity of a second kinase appeared after 1
      hr and was responsible for the continuing phosphorylation of the H+-ATPase. This
      latter Ca2+-dependent kinase was inhibited by a calmodulin (CaM) antagonist and
      by an inhibitor of Ca2+/CaM-dependent protein kinase II. The activation of the
      Ca2+/CaM-dependent protein kinase depended on the prior activation of the PKC
      like kinase.

PMID- 12239393
TI  - The Light-Dependent Transduction Pathway Controlling the Regulatory
      Phosphorylation of C4 Phosphoenolpyruvate Carboxylase in Protoplasts from
      Digitaria sanguinalis.
AB  - Phosphoenolpyruvate carboxylase (PEPC) was characterized in extracts from C4
      mesophyll protoplasts isolated from Digitaria sanguinalis leaves and shown to
      display the structural, functional, and regulatory properties typical of a C4
      PEPC. In situ increases in the apparent phosphorylation state of the enzyme and
      the activity of its Ca2+-independent protein-serine kinase were induced by light
      plus NH4Cl or methylamine. The photosynthesis-related metabolite 3
      phosphoglycerate (3-PGA) was used as a substitute for the weak base in these
      experiments. The early effects of light plus the weak base or 3-PGA treatment
      were alkalinization of protoplast cytosolic pH, shown by fluorescence cytometry,
      and calcium mobilization from vacuoles, as suggested by the use of the calcium
      channel blockers TMB-8 and verapamil. The increases in PEPC kinase activity and
      the apparent phosphorylation state of PEPC also were blocked in situ by the
      electron transport and ATP synthesis inhibitors DCMU and gramicidin,
      respectively, the calcium/calmodulin antagonists W7, W5, and compound 48/80, and
      the cytosolic protein synthesis inhibitor cycloheximide. These results suggest
      that the production of ATP and/or NADPH by the illuminated mesophyll chloroplast
      is required for the activation of the transduction pathway, which presumably
      includes an upstream Ca2+-dependent protein kinase and a cytosolic protein
      synthesis event. The collective data support the view that the C4 PEPC light
      transduction pathway is contained entirely within the mesophyll cell and imply
      cross-talk between the mesophyll and bundle sheath cells in the form of the
      photosynthetic metabolite 3-PGA.

PMID- 12239394
TI  - SOS1, a Genetic Locus Essential for Salt Tolerance and Potassium Acquisition.
AB  - To begin to determine which genes are essential for salt tolerance in higher
      plants, we identified four salt-hypersensitive mutants of Arabidopsis by using a
      root-bending assay on NaCl-containing agar plates. These mutants (sos1-1, sos1-2,
      sos1-3, and sos1-4) are allelic to each other and were caused by single recessive
      nuclear mutations. The SOS1 gene was mapped to chromosome 2 at 29.5 [plusmn] 6.1
      centimorgans. The mutants showed no phenotypic changes except that their growth
      was >20 times more sensitive to inhibition by NaCl. Salt hypersensitivity is a
      basic cellular trait exhibited by the mutants at all developmental stages. The
      sos1 mutants are specifically hypersensitive to Na+ and Li+. The mutants were
      unable to grow on media containing low levels (below ~1 mM) of potassium. Uptake
      experiments using 86Rb showed that sos1 mutants are defective in high-affinity
      potassium uptake. sos1 plants became deficient in potassium when treated with
      NaCl. The results demonstrate that potassium acquisition is a critical process
      for salt tolerance in glycophytic plants.

PMID- 12239395
TI  - Modification of a Specific Class of Plasmodesmata and Loss of Sucrose Export
      Ability in the sucrose export defective1 Maize Mutant.
AB  - We report on the export capability and structural and ultrastructural
      characteristics of leaves of the sucrose export defective1 (sed1; formerly called
      sut1) maize mutant. Whole-leaf autoradiography was combined with light and
      transmission electron microscopy to correlate leaf structure with differences in
      export capacity in both wild-type and sed1 plants. Tips of sed1 blades had
      abnormal accumulations of starch and anthocyanin and distorted vascular tissues
      in the minor veins, and they did not export sucrose. Bases of sed1 blades were
      structurally identical to those of the wild type and did export sucrose. Electron
      microscopy revealed that only the plasmodesmata at the bundle sheath-vascular
      parenchyma cell interface in sed1 minor veins were structurally modified.
      Aberrant plasmodesmal structure at this critical interface results in a
      symplastic interruption and a lack of phloem-loading capability. These results
      clarify the pathway followed by photosynthates, the pivotal role of the
      plasmodesmata at the bundle sheath-vascular parenchyma cell interface, and the
      role of the vascular parenchyma cells in phloem loading.

PMID- 12239396
TI  - Duplications That Suppress and Deletions That Restore Expression from a Chalcone
      Synthase Multigene Family.
AB  - Seed coat color in soybean is determined by four alleles of the classically
      defined / (inhibitor) locus that controls the presence or absence as well as the
      spatial distribution of anthocyanin pigments in the seed coat. By analyzing
      spontaneous mutations of the / locus, we demonstrated that the / locus is a
      region of chalcone synthase (CHS) gene duplications. Paradoxically, deletions of
      CHS gene sequences allow higher levels of CHS mRNAs and restore pigmentation to
      the seed coat. The unusual nature of the / locus suggests that its dominant
      alleles may represent naturally occurring examples of homology-dependent gene
      silencing and that the spontaneous deletions erase the gene-silencing phenomena.
      Specifically, mutations from the dominant ii allele (yellow seed coats with
      pigmented hila) to the recessive i allele (fully pigmented) can be associated
      with the absence of a 2.3-kb Hindlll fragment that carries CHS4, a member of the
      multigene CHS family. Seven independent mutations exhibit deletions in the CHS4
      promoter region. The dominant / allele (yellow seed coats) exhibits an extra 12.1
      kb Hindlll fragment that hybridizes with both the CHS coding region and CHS1
      promoter-specific probes. Mutations of the dominant / allele to the recessive i
      allele (pigmented seed coats) give rise to 10.4- or 9.6-kb Hindlll CHS fragments
      that have lost the duplicated CHS1 promoter. Finally, gene expression analysis
      demonstrated that heterozygous plants (I/i) with yellow seed coats have reduced
      mRNA levels, indicating that the 12.1-kb Hindlll CHS fragment associated with the
      dominant / allele inhibits pigmentation in a trans-dominant manner. Moreover, CHS
      gene-specific expression in seed coats shows that multiple CHS genes are
      expressed in seed coats.

PMID- 12239397
TI  - Increased Phosphorylation of a 26-kD Pollen Protein Is Induced by the Self
      Incompatibility Response in Papaver rhoeas.
AB  - We have investigated whether specific protein phosphorylation events are induced
      in Papaver rhoeas pollen as a consequence of the self-incompatibility (SI)
      response. Pollen grown in vitro in the presence of 32P-orthophosphate was
      challenged with biologically active recombinant S proteins, and pollen proteins
      were extracted and analyzed. The results provide strong evidence that the
      increased phosphorylation of a 26-kD protein of pl 6.2, p26, is specifically
      induced by the SI response. This phosphorylation event occurs in living pollen
      tubes and was observed specifically when pollen was challenged with S proteins
      that are incompatible with the S alleles carried by the pollen and not when
      pollen was challenged with compatible or incompatible heat-denatured S proteins.
      Further characterization demonstrated that p26 comprises two phosphoproteins,
      p26.1 and p26.2, that are found in soluble and microsomal fractions,
      respectively. Increased phosphorylation of p26.1 is implicated in the SI response
      and appears to be Ca2+ and calmodulin dependent. These data argue for the
      involvement of a Ca2+-dependent protein kinase requiring calmodulin-like domains,
      whose activation comprises an intracellular signal mediating the SI response in
      P. rhoeas pollen.

PMID- 12239398
TI  - PORA and PORB, Two Light-Dependent Protochlorophyllide-Reducing Enzymes of
      Angiosperm Chlorophyll Biosynthesis.

PMID- 12239399
TI  - Regulatory Genes Controlling MPG1 Expression and Pathogenicity in the Rice Blast
      Fungus Magnaporthe grisea.
AB  - MPG1, a pathogenicity gene of the rice blast fungus Magnaporthe grisea, is
      expressed during pathogenesis and in axenic culture during nitrogen or glucose
      limitation. We initiated a search for regulatory mutations that would impair
      nitrogen metabolism, MPG1 gene expression, and pathogenicity. First, we developed
      a pair of laboratory strains that were highly fertile and pathogenic toward
      barley. Using a combinatorial genetic screen, we identified mutants that failed
      to utilize a wide range of nitrogen sources (e.g., nitrate or amino acids) and
      then tested the effect of these mutations on pathogenicity. We identified five
      mutants and designated them Nr- (for nitrogen regulation defective). We show that
      two of these mutations define two genes, designated NPR1 and NPR2 (for nitrogen
      pathogenicity regulation), that are essential for pathogenicity and the
      utilization of many nitrogen sources. These genes are nonallelic to the major
      nitrogen regulatory gene in M. grisea and are required for expression of the
      pathogenicity gene MPG1. We propose that NPR1 and NPR2 are major regulators of
      pathogenicity in M. grisea and may be novel regulators of nitrogen metabolism in
      fungi.

PMID- 12239400
TI  - Pattern Formation in the Arabidopsis Embryo Revealed by Position-Specific Lipid
      Transfer Protein Gene Expression.
AB  - During Arabidopsis embryogenesis, the zygote divides asymmetrically in the future
      apical-basal axis; however, a radial axis is initiated only within the eight
      celled embryo. Mutations in the GNOM, KNOLLE, and KEULE genes affect these
      processes: gnom zygotes tend to divide symmetrically; knolle embryos lack
      oriented cell divisions that initiate protoderm formation; and in keule embryos,
      an outer cell layer is present that consists of abnormally enlarged cells from
      early development. Pattern formation along the two axes is reflected by the
      position-specific expression of the Arabidopsis lipid transfer protein (AtLTP1)
      gene. In wild-type embryos, the AtLTP1 gene is expressed in the protoderm and
      initially in all protodermal cells; later, AtLTP1 expression is confined to the
      cotyledons and the upper end of the hypocotyl. Analysis of AtLTP1 expression in
      gnom, knolle, and keule embryos showed that gnom embryos also can have no or
      reversed apical-basal polarity, whereas radial polarity is unaffected. knolle
      embryos initially lack but eventually form a radial pattern, and keule embryos
      are affected in protoderm cell morphology rather than in the establishment of the
      radial pattern.

PMID- 12239401
TI  - Systemic Acquired Resistance Mediated by the Ectopic Expression of Invertase:
      Possible Hexose Sensing in the Secretory Pathway.
AB  - Systemic acquired resistance (SAR) has been reported to be associated with lesion
      mimic mutants. Tobacco plants expressing vacuolar and apoplastic yeast-derived
      invertase (vaclnv and cwlnv, respectively) develop spontaneous necrotic lesions
      similar to hypersensitive responses caused by avirulent pathogens. Therefore, SAR
      and metabolic alterations leading to the activation of defense-related responses
      were studied in these plants. Defense-related gene transcripts, callose content,
      peroxidase activities, and levels of salicylic acid were found to be elevated.
      The defense reactions were accompanied by increased resistance toward potato
      virus Y and were measured as decreased viral spreading and reduced multiplication
      in systemic leaves of the transgenic plants. Interestingly, the accumulation of
      pathogenesis-related (PR) protein transcripts (PR-Q) and repression of
      photosynthetic gene transcripts (chlorophyll a/b binding protein) were inversely
      correlated and required the same threshold level of hexoses for induction and
      repression. Expression of a cytosolic yeast-derived invertase in transgenic
      tobacco plants with equally increased levels of sugars neither displayed SAR
      responses nor showed decreased levels of photosynthetic genes. It is suggested
      that hexose sensing in the secretory pathway is essential for mediating the
      activation of defense-related genes as well as repression of photosynthetic genes
      in vaclnv and cwlnv plants.

PMID- 12239402
TI  - Sperm Identification in Maize by Fluorescence in Situ Hybridization.
AB  - The two sperm cells of common origin within the pollen tube of flowering plants
      are each involved in a fertilization event. It has long been recognized that
      preferential fusion of one sperm with the egg can occur in B chromosome
      containing lines of maize. If the second pollen mitosis begins with a single B
      chromosome, nondisjunction will result in one sperm possessing two B chromosomes
      and the other containing no B chromosomes. The B chromosome-containing sperm most
      often fertilizes the egg, whereas the sperm nucleus with no B chromosomes fuses
      with the polar nuclei. Despite the obvious advantages of being able to recognize
      and then track, separate, and analyze one sperm type from the other, it has not
      been possible because of the lack of sufficient detectable differences between
      the two types of sperms. In this study, we used a B chromosome-specific DNA
      sequence (pZmBs) and in situ hybridization to identify and track the B chromosome
      containing sperm cell within mature pollen and pollen tubes. Our results are
      consistent with conclusions from previous genetic studies related to B chromosome
      behavior during pollen formation. Within pollen tubes, the position in which the
      B chromosome-containing sperm travels (leading or trailing) in relation to the
      sperm cell lacking B chromosomes appears to be random.

PMID- 12239403
TI  - Localization of T-DNA Insertions in Petunia by Fluorescence in Situ
      Hybridization: Physical Evidence for Suppression of Recombination.
AB  - Using fluorescence in situ hybridization (FISH) with metaphase preparations, we
      localized a 4-kb single-copy T-DNA sequence in a group of petunia transformants.
      The selected T-DNAs previously had been shown to be linked to the phenotypic
      marker FI on chromosome II. Linkage analysis had revealed that recombination
      around the FI locus is suppressed in a wide cross relative to an inbred
      recombination assay. The localization of six FI-linked T-DNAs and the FI locus
      itself, using FISH, revealed a number of aspects of recombination in petunia: (1)
      the central region of chromosome II showed at least a 10-fold suppression of
      recombination in wide crosses relative to the distal region; (2) recombination in
      wide hybrids over two-thirds of the chromosome was extremely low; and (3)
      recombination between completely homologous chromosomes in an inbred cross also
      was suppressed in the central region. In addition, the T-DNAs were not evenly
      distributed along the chromosome, suggesting a possible preference for a distal
      position for T-DNA integration. Implications for such a preference are discussed.

PMID- 12239404
TI  - Two Small Spatially Distinct Regions of Phytochrome B Are Required for Efficient
      Signaling Rates.
AB  - We used a series of in vitro-generated deletion and amino acid substitution
      derivatives of phytochrome B (phyB) expressed in transgenic Arabidopsis to
      identify regions of the molecule important for biological activity. Expression of
      the chromophore-bearing N-terminal domain of phyB alone resulted in a fully
      photoactive, monomeric molecule lacking normal regulatory activity. Expression of
      the C-terminal domain alone resulted in a photoinactive, dimeric molecule, also
      lacking normal activity. Thus, both domains are necessary, but neither is
      sufficient for phyB activity. Deletion of a small region on each major domain
      (residues 6 to 57 and 652 to 712, respectively) was shown to compromise phyB
      activity differentially without interfering with spectral activity or
      dimerization. Deletion of residues 6 to 57 caused a large increase in the fluence
      rate of continuous red light (Rc) required for maximal seedling responsiveness,
      indicating a marked decrease in efficiency of light signal perception or
      processing per mole of mutant phyB. In contrast, deletion of residues 652 to 712
      resulted in a photoreceptor that retained saturation of seedling responsiveness
      to Rc at low fluence rates but at a response level much below the maximal
      response elicited by the parent molecule. This deletion apparently reduces the
      maximal biological activity per mole of phyB without a major decrease in
      efficiency of signal perception, thus suggesting disruption of a process
      downstream of signal perception. In addition, certain phyB constructs caused
      dominant negative interference with endogenous phyA activity in continuous far
      red light, suggesting that the two photoreceptors may share reaction partners.

PMID- 12239405
TI  - bundle sheath defective2, a Mutation That Disrupts the Coordinated Development of
      Bundle Sheath and Mesophyll Cells in the Maize Leaf.
AB  - Within the maize leaf primordium, coordinated cell division and differentiation
      patterns result in the development of two morphologically and biochemically
      distinct photosynthetic cell types, the bundle sheath and the mesophyll. The
      bundle sheath defective2-mutable1 (bsd2-m1) mutation specifically disrupts C4
      differentiation in bundle sheath cells in that the levels of bundle sheath cell
      specific photosynthetic enzymes are reduced and the bundle sheath chloroplast
      structure is aberrant. In contrast, mesophyll cell-specific enzymes accumulate to
      normal levels, and the mesophyll cell chloroplast structure is not perturbed.
      Throughout mutant leaf development, the large and small subunits of ribulose
      bisphosphate carboxylase are absent; however, both rbcL and RbcS transcripts
      accumulate. Moreover, chloroplast-encoded rbcL transcripts accumulate ectopically
      in mesophyll cells. Although the bundle sheath cell chloroplast structure
      deteriorates rapidly when plants are exposed to light, this deterioration is most
      likely a secondary effect resulting from cell-specific photooxidative damage.
      Therefore, we propose that the Bsd2 gene plays a direct role in the post
      transcriptional control of rbcL transcript accumulation and/or translation, both
      in bundle sheath and mesophyll cells, and an indirect role in the maintenance of
      bundle sheath cell chloroplast structure.

PMID- 12239406
TI  - A High-Affinity Binding Site for the AVR9 Peptide Elicitor of Cladosporium fulvum
      Is Present on Plasma Membranes of Tomato and Other Solanaceous Plants.
AB  - The race-specific Cladosporium fulvum peptide elicitor AVR9, which specifically
      induces a hypersensitive response in tomato genotypes carrying the Cf-9
      resistance gene, was labeled with iodine-125 at the N-terminal tyrosine residue
      and used in binding studies. 125I-AVR9 showed specific, saturable, and reversible
      binding to plasma membranes isolated from leaves of tomato cultivar Moneymaker
      without Cf resistance genes (MM-Cf0) or from a near-isogenic genotype with the Cf
      9 resistance gene (MM-Cf9). The dissociation constant was found to be 0.07 nM,
      and the receptor concentration was 0.8 pmol/mg microsomal protein. Binding was
      highly influenced by pH and the ionic strength of the binding buffer and by
      temperature, indicating the involvement of both electrostatic and hydrophobic
      interactions. Binding kinetics and binding capacity were similar for membranes of
      the MM-Cf0 and MM-Cf9 genotypes. In all solanaceous plant species tested, an AVR9
      binding site was present, whereas in the nonsolanaceous species that were
      analyzed, such a binding site could not be identified. The ability of membranes
      isolated from different solanaceous plant species to bind AVR9 seems to correlate
      with the presence of members of the Cf-9 gene family, but whether this
      correlation is functional remains to be determined.

PMID- 12239407
TI  - S RNase and Interspecific Pollen Rejection in the Genus Nicotiana: Multiple
      Pollen-Rejection Pathways Contribute to Unilateral Incompatibility between Self
      Incompatible and Self-Compatible Species.
AB  - In self-incompatible (SI) plants, the S locus acts to prevent growth of self
      pollen and thus promotes outcrossing within the species. Interspecific crosses
      between SI and self-compatible (SC) species often show unilateral incompatibility
      that follows the SI x SC rule: SI species reject pollen from SC species, but the
      reciprocal crosses are usually compatible. The general validity of the SI x SC
      rule suggests a link between SI and interspecific pollen rejection; however, this
      link has been questioned because of a number of exceptions to the rule. To
      clarify the role of the S locus in interspecific pollen rejection, we transformed
      several Nicotiana species and hybrids with genes encoding SA2 or SC10 RNase from
      SI N. alata. Compatibility phenotypes in the transgenic plants were tested using
      pollen from three SC species showing unilateral incompatibility with N. alata. S
      RNase was implicated in rejecting pollen from all three species. Rejection of N.
      plumbaginifolia pollen was similar to S allele-specific pollen rejection, showing
      a requirement for both S RNase and other genetic factors from N. alata. In
      contrast, S RNase-dependent rejection of N. glutinosa and N. tabacum pollen
      proceeded without these additional factors. N. alata also rejects pollen from the
      latter two species through an S RNase-independent mechanism. Our results
      implicate the S locus in all three systems, but it is clear that multiple
      mechanisms contribute to interspecific pollen rejection.

PMID- 12239408
TI  - The Miniature1 Seed Locus of Maize Encodes a Cell Wall Invertase Required for
      Normal Development of Endosperm and Maternal Cells in the Pedicel.
AB  - Collective evidence demonstrates that the Miniature1 (Mn1) seed locus in maize
      encodes an endosperm-specific isozyme of cell wall Invertase, CWI-2. The evidence
      includes (1) isolation and characterization of ethyl methanesulfonate-induced mn1
      mutants with altered enzyme activity and (2) a near-linear relationship between
      gene/dose and invertase activity and the CWI-2 protein. In addition, molecular
      analyses showed that the cDNA clone incw2 maps to the Mn1 locus and
      differentiates the six ethyl methanesulfonate-induced mn1 mutants of independent
      origin into two classes when RNA gel blot analyses were used. We also report two
      unexpected observations that provide significant new insight into the
      physiological role of invertase and its regulation in a developing seed. First, a
      large proportion of total enzyme activity (~90%) was dispensable (i.e.,
      nonlimiting). However, below the threshold level of ~6% of wild-type activity,
      the endosperm enzyme controlled both the sink strength of the developing
      endosperm as well as the developmental stability of maternal cells in the pedicel
      in a rate-limiting manner. Our data also suggest an unusually tight coordinate
      control between the cell wall-bound and the soluble forms of invertase, which are
      most likely encoded by two separate genes, presumably through metabolic controls
      mediated by the sugars.

PMID- 12239409
TI  - MPG1 Encodes a Fungal Hydrophobin Involved in Surface Interactions during
      Infection-Related Development of Magnaporthe grisea.
AB  - The rice blast fungus expresses a pathogenicity gene, MPG1, during appressorium
      formation, disease symptom development, and conidiation. The MPG1 gene sequence
      predicts a small protein belonging to a family of fungal proteins designated
      hydrophobins. Using random ascospore analysis and genetic complementation, we
      showed that MPG1 is necessary for infection-related development of Magnaporthe
      grisea on rice leaves and for full pathogenicity toward susceptible rice
      cultivars. The protein product of MPG1 appears to interact with hydrophobic
      surfaces, where it may act as a developmental sensor for appressorium formation.
      Ultrastructural studies revealed that MPG1 directs formation of a rodlet layer on
      conidia composed of interwoven ~5-nm rodlets, which contributes to their surface
      hydrophobicity. Using combined genetic and biochemical approaches, we identified
      a 15-kD secreted protein with characteristics that establish it as a class I
      hydrophobin. The protein is able to form detergent-insoluble high molecular mass
      complexes, is soluble in trifluoroacetic acid, and exhibits mobility shifts after
      treatment with performic acid. The production of this protein is directed by
      MPG1.

PMID- 12239410
TI  - Decreased Susceptibility to Viral Disease of [beta]-1,3-Glucanase-Deficient
      Plants Generated by Antisense Transformation.
AB  - Antifungal class I [beta]-1,3-glucanases are believed to be part of the
      constitutive and induced defenses of plants against fungal infection.
      Unexpectedly, mutants deficient in these enzymes generated by antisense
      transformation showed markedly reduced lesion size, lesion number, and virus
      yield in the local-lesion response of Havana 425 tobacco to tobacco mosaic virus
      (TMV) and of Nicotiana sylvestris to tobacco necrosis virus. These mutants also
      showed decreased severity of mosaic disease symptoms, delayed spread of symptoms,
      and reduced yield of virus in the susceptible response of N. sylvestris to TMV.
      The symptoms of disease in the responses of both plant species were positively
      correlated with [beta]-1,3-glucanase content in a series of independent
      transformants. Taken together, these results provide direct evidence that [beta]
      1,3-glucanases function in viral pathogenesis. Callose, a substrate for [beta]
      1,3-glucanase, acts as a physical barrier to the spread of virus. Callose
      deposition in and surrounding TMV-induced lesions was increased in the [beta]-1,3
      glucanase-deficient, local-lesion Havana 425 host, suggesting as a working
      hypothesis that decreased susceptibility to virus resulted from increased
      deposition of callose in response to infection. Our results suggest novel means,
      based on antisense transformation with host genes, for protecting plants against
      viral infection. These observations also raise the intriguing possibility that
      viruses can use a defense response of the host against fungal
      infection[mdash]production of [beta]-1,3-glucanases[mdash]to promote their own
      replication and spread.

PMID- 12239411
TI  - Abscisic Acid Induces Mitogen-Activated Protein Kinase Activation in Barley
      Aleurone Protoplasts.
AB  - Abscisic acid (ABA) induces a rapid and transient mitogen-activated protein (MAP)
      kinase activation in barley aleurone protoplasts. MAP kinase activity, measured
      as myelin basic protein phosphorylation by MAP kinase immunoprecipitates,
      increased after 1 min, peaked after 3 min, and decreased to basal levels after ~5
      min of ABA treatment in vivo. Antibodies recognizing phosphorylated tyrosine
      residues precipitate with myelin basic protein kinase activity that has identical
      ABA activation characteristics and demonstrate that tyrosine phosphorylation of
      MAP kinase occurs during activation. The half-maximal concentration of ABA
      required for MAP kinase activation, 3 x 10-7 M, is very similar to that required
      for ABA-induced rab16 gene expression. The tyrosine phosphatase inhibitor
      phenylarsine oxide can completely block ABA-induced MAP kinase activation and
      rab16 gene expression. These results lead us to conclude that ABA activates MAP
      kinase via a tyrosine phosphatase and that these steps are a prerequisite for ABA
      induction of rab16 gene expression.

PMID- 12239412
TI  - Changes in the Plasma Membrane Distribution of Rice Phospholipase D during
      Resistant Interactions with Xanthomonas oryzae pv oryzae.
AB  - Phospholipase D (PLD; EC 3.1.4.4), which hydrolyzes phospholipids to generate
      phosphatidic acid, was examined in rice leaves undergoing susceptible or
      resistant interactions with Xanthomonas oryzae pv oryzae. RNA analysis of leaves
      undergoing resistant interactions revealed different expression patterns for PLD
      over 5 days relative to control plants or those undergoing susceptible
      interactions. By using an activity assay and immunoblot analysis, we identified
      three forms of PLD (1, 2, and 3). PLD 1 was observed only at 1 day after tissue
      infiltration. PLDs 2 and 3 were detected up to 3 days in all interactions.
      Immunoelectron microscopy studies revealed PLD to be associated predominantly
      with the plasma membrane. In cells undergoing a susceptible response, PLD was
      uniformly distributed along the plasma membrane at 3, 6, 12, and 24 hr after
      inoculation. However, within 12 hr after bacterial challenge in resistant
      interactions, PLD was clustered preferentially in membranes adjacent to bacterial
      cells.

PMID- 12239413
TI  - A Single Gene May Encode Differentially Localized Ca2+-ATPases in Tomato.
AB  - Previously, a partial-length cDNA and a complete genomic clone encoding a
      putative sarcoplasmic reticulum-type Ca2+-ATPase (LCA, Lycopersicon Ca2+-ATPase)
      were isolated from tomato. To determine the subcellular localization of this Ca2+
      ATPase, specific polyclonal antibodies raised against a fusion protein encoding a
      portion of the LCA polypeptide were generated. Based on hybridization of the LCA
      cDNA and of the nucleotide sequence encoding the fusion protein to genomic DNA,
      it appears that LCA and the fusion protein domain are encoded by a single gene in
      tomato. Antibodies raised against the LCA domain fusion protein reacted
      specifically with two polypeptides of 116 and 120 kD that are localized in the
      vacuolar and plasma membranes, respectively. The distribution of vanadate
      sensitive ATP-dependent Ca2+ transport activities in sucrose gradients coincided
      with the distribution of the immunodetected proteins. The ATP-dependent Ca2+
      transport activities associated with tonoplast and plasma membrane fractions
      shared similar properties, because both fractions were inhibited by vanadate but
      insensitive to carbonyl cyanide m-chlorophenylhydrazone, nitrate, and calmodulin.
      Moreover, antibodies raised against the LCA domain fusion protein inhibited ATP
      dependent Ca2+ uptake activity associated with both the tonoplast and plasma
      membrane fractions. These data suggest that a single gene (LCA) may encode two P
      type Ca2+-ATPase isoforms that are differentially localized in the tonoplast and
      plasma membrane of tomato roots.

PMID- 12239414
TI  - A Similar Dichotomy of Sugar Modulation and Developmental Expression Affects Both
      Paths of Sucrose Metabolism: Evidence from a Maize Invertase Gene Family.
AB  - Invertase and sucrose synthase catalyze the two known paths for the first step in
      carbon use by sucrose-importing plant cells. The hypothesis that sugar-modulated
      expression of these genes could provide a means of import adjustment was
      initially suggested based on data from sucrose synthases alone; however, this
      hypothesis remained largely conjectural without critical evidence for invertases.
      Toward this end, a family of maize invertases was cloned and characterized. Here,
      we show that invertases are indeed sugar modulated and, surprisingly, like the
      sucrose synthase genes, fall into two classes with contrasting sugar responses.
      In both families, one class of genes is upregulated by increasing carbohydrate
      supply (Sucrose synthase1 [Sus1] and Invertase2 [Ivr2]), whereas a second class
      in the same family is repressed by sugars and upregulated by depletion of this
      resource (Shrunken1 [Sh1] and Invertase1 [Ivr1]). The two classes also display
      differential expression during development, with sugar-enhanced genes (Sus1 and
      Ivr2) expressed in many importing organs and sugar-repressed, starvation-tolerant
      genes (Sh1 and Ivr1) upregulated primarily during reproductive development. Both
      the Ivr1 and Ivr2 invertase mRNAs are abundant in root tips, very young kernels,
      silk, anthers, and pollen, where a close relationship is evident between changes
      in message abundance and soluble invertase activity. During development, patterns
      of expression shift as assimilate partitioning changes from elongating silks to
      newly fertilized kernels. Together, the data support a model for integrating
      expression of genes differentially responsive to carbohydrate availability (i.e.,
      feast and famine conditions) with developmental signals. The demonstration that
      similar regulatory patterns occur in both paths of sucrose metabolism indicates a
      potential to influence profoundly the adjustment of carbon resource allocation.

PMID- 12239415
TI  - Growth of Pollen Tubes of Papaver rhoeas Is Regulated by a Slow-Moving Calcium
      Wave Propagated by Inositol 1,4,5-Trisphosphate.
AB  - A signaling role for cytosolic free Ca2+ ([Ca2+]i) in regulating Papaver rhoeas
      pollen tube growth during the self-incompatibility response has been demonstrated
      previously. In this article, we investigate the involvement of the
      phosphoinositide signal transduction pathway in Ca2+-mediated pollen tube
      inhibition. We demonstrate that P. rhoeas pollen tubes have a Ca2+-dependent
      polyphosphoinositide-specific phospholipase C activity that is inhibited by
      neomycin. [Ca2+]i imaging after photolysis of caged inositol (1,4,5)
      trisphosphate (Ins[1,4,5]P3) in pollen tubes demonstrated that Ins(1,4,5)P3 could
      induce Ca2+ release, which was inhibited by heparin and neomycin. Mastoparan,
      which stimulated Ins(1,4,5)P3 production, also induced a rapid increase in Ca2+,
      which was inhibited by neomycin. These data provide direct evidence for the
      involvement of a functional phosphoinositide signal-transducing system in the
      regulation of pollen tube growth. We suggest that the observed Ca2+ increases are
      mediated, at least in part, by Ins(1,4,5)P3-induced Ca2+ release. Furthermore, we
      provide data suggesting that Ca2+ waves, which have not previously been reported
      in plant cells, can be induced in pollen tubes.

PMID- 12239416
TI  - Preamylopectin Processing: A Mandatory Step for Starch Biosynthesis in Plants.
AB  - It has been generally assumed that the [alpha]-(1->4)-linked and [alpha]-(1->6)
      branched glucans of starch are generated by the coordinated action of elongation
      (starch synthases) and branching enzymes. We have identified a novel
      Chlamydomonas locus (STA7) that when defective leads to a wipeout of starch and
      its replacement by a small amount of glycogen-like material. Our efforts to
      understand the enzymological basis of this phenotype have led us to determine the
      selective disappearance of an 88-kD starch hydrolytic activity. We further
      demonstrate that this enzyme is a debranching enzyme. Cleavage of the [alpha]-(1
      >6) linkage in a branched precursor of amylopectin (preamylopectin) has provided
      us with the ground rules for understanding starch biosynthesis in plants.
      Therefore, we propose that amylopectin clusters are synthesized by a
      discontinuous mechanism involving a highly specific glucan trimming mechanism.

PMID- 12239417
TI  - Disease Lesion Mimicry Caused by Mutations in the Rust Resistance Gene rp1.
AB  - The rp1 locus of maize controls race-specific resistance to the common rust
      fungus Puccinia sorghi. Four mutant or recombinant Rp1 alleles (rp1-NC3, Rp1-D21,
      Rp1-MD19, and Rp1-Kr1N) were identified. They condition necrotic phenotypes in
      the absence of the rust pathogen. These Rp1 lesion mimics fall into three
      different phenotypic classes: (1) The rp1-NC3 and Rp1-D21 alleles require rust
      infection or other biotic stimulus to initiate necrotic lesions. These alleles
      react strongly to all maize rust biotypes tested and also to nonhost rusts. (2)
      The Rp1-MD19 allele, which has a similar phenotype, also requires a biotic
      stimulus to initiate lesions. However, Rp1-MD19 shows the race specificity of the
      Rp1-D gene. (3) The Rp1-Kr1N allele specifies a diffuse necrotic phenotype in the
      absence of any biotic stimulus and a race-specific reaction when inoculated with
      maize rust.

PMID- 12239418
TI  - Embryo Sac Development in the Maize indeterminate gametophyte1 Mutant: Abnormal
      Nuclear Behavior and Defective Microtubule Organization.
AB  - The indeterminate gametophyte1 mutation in maize has been known to disrupt
      development of the female gametophyte. Mutant embryo sacs have abnormal numbers
      and behavior of micropylar and central cell nuclei, which result in polyembryony
      and elevated ploidy levels in the endosperm of developing kernels. In this study,
      we confirm abnormal nuclear behavior and present novel findings. In contrast to
      the normal form, there is no obvious polarity in two-nucleate embryo sacs or in
      the micropylar cells of eight-nucleate embryo sacs. We show that the second and
      third mitoses are not fully synchronized and that additional mitoses can occur in
      all of the nuclei of the mutant embryo sac or in just the micropylar or central
      regions. After cellularization, individual micropylar cells can undergo mitosis.
      Abnormal microtubular behavior results in irregular positioning of the nuclei,
      asynchronous microtubular patterns in different pairs of nuclei, and abnormal
      phragmoplasts after the third mitotic division. These results indicate that in
      addition to acting primarily in controlling nuclear divisions, the indeterminate
      gametophyte1 gene acts secondarily in regulating microtubule behavior. This
      cytoskeletal activity most likely controls the polarization and nuclear migration
      underlying the formation and fate of the cells of the normal embryo sac.

PMID- 12239419
TI  - Approaching the Lower Limits of Transgene Variability.
AB  - The inclusion of chicken lysozyme matrix-associated regions (MARs) in T-DNA has
      been demonstrated to reduce the variation in [beta]-glucuronidase (GUS) gene
      expression among first-generation transformed plants. The residual variation
      observed between transgenic plant lines with MARs at the T-DNA borders was
      investigated. By definition, any phenotypic variance between or within
      genetically identical plants is caused by random or environmental variation. This
      variation therefore sets a lower limit to the variation in GUS activities. The
      variance of GUS activity in offspring plant populations of genetically identical
      individuals was used as an estimate of environmental variation. For transgenic
      plants with MARs at the T-DNA borders, the variation between independent
      transformants could not be distinguished from the environmental variation. The
      variation could be attributed mainly to the variation in the GUS activity
      measurement. Therefore, the MAR element approached the maximal possible reduction
      of transgene variability given current technology and sample sizes. The role of
      MARs in offspring plants was evaluated by comparing such populations of
      transgenic plants for the magnitude of and variation in GUS activity. Pairwise
      comparisons showed that the presence of MARs reduced variation in offspring
      generations in the same manner as demonstrated for primary transformants. The
      populations carrying a doubled cauliflower mosaic virus 35S promoter-GUS gene
      tended to be more variable than the Lhca3.St.1 promoter-GUS gene-carrying
      populations. This tendency indicated an intrinsic susceptibility of the doubled
      cauliflower mosaic virus 35S promoter to variation. Homozygous plants were
      approximately twice as active as the corresponding hemizygous plants and tended
      to be more variable than the hemizygous plants. We hypothesized that the
      magnitude of environmental variations is related to a higher susceptibility to
      transgene silencing.

PMID- 12239420
TI  - Free Radicals and Skin. Proceedings of the 4th Teupitzer Colloquium. September 28
      to October 1, 2001.

PMID- 12239421
TI  - Antioxidants and the response of skin to oxidative stress: vitamin E as a key
      indicator.
AB  - As the outermost barrier of the body, the skin is directly and frequently exposed
      to a prooxidative environment, including solar UVA and UVB radiation, and air
      pollution. The skin is equipped with an elaborate system of antioxidant
      substances and enzymes that includes a network of redox active antioxidants.
      Among these, vitamin E has been identified as the predominant antioxidant both in
      murine and human skin and shows a characteristic gradient with lower levels
      towards the outer stratum corneum layers. Skin exposure to UV and ozone alone and
      in combination resulted in a significant potentiation of the UV-induced vitamin E
      depletion. Oxidants and antioxidants play an important role in maintaining a
      balance between free radicals produced by metabolism or derived from
      environmental sources. Cellular antioxidants may change their redox state, be
      targeted for destruction, regulate oxidative process involved in signal
      transduction, affect gene expression and pathways of cell proliferation and
      death. Here we provide an overview of the antioxidant system with a special
      relevance to skin.

PMID- 12239422
TI  - Carotenoids and protection against solar UV radiation.
AB  - Upon exposure to UV light photooxidative reactions are initiated which are
      damaging to biomolecules and affect the integrity of cells and tissues.
      Photooxidative damage plays a role in pathological processes and is involved in
      the development of disorders affecting the skin. When skin is exposed to UV
      light, erythema is observed as an initial reaction. Carotenoids like beta
      carotene or lycopene are efficient antioxidants scavenging singlet molecular
      oxygen and peroxyl radicals generated in during photooxidation. When beta
      carotene was applied as such or in combination with alpha-tocopherol for 12
      weeks, erythema formation induced with a solar light simulator was diminished
      from week 8 on. Similar effects were also achieved with a diet rich in lycopene.
      Ingestion of tomato paste corresponding to a dose of 16 mg lycopene/ day over 10
      weeks led to increases in serum levels of lycopene and total carotenoids in skin.
      At week 10, erythema formation was significantly lower in the group that ingested
      the tomato paste as compared to the control group. No significant difference was
      found at week 4 of treatment. Thus, protection against UV light-induced erythema
      can be achieved by ingestion of a commonly consumed dietary source of lycopene.
      Such protective effects of carotenoids were also demonstrated in cell culture.
      The in-vitro data indicate that there is an optimal level of protection for each
      carotenoid.

PMID- 12239423
TI  - Photochemoprevention by botanical antioxidants.
AB  - The trend towards an increase in incidence and higher prevalence of skin cancer
      makes identification of effective chemopreventive agents an urgent priority.
      Excessive exposure to solar ultraviolet (UV) B radiation has been implicated as
      its main cause. Since these trends are likely to continue in the foreseeable
      future, the adverse effect of UVB has become a major human health concern.
      Therefore, the development of novel strategies to reduce the occurrence of skin
      cancer has become a highly desirable goal. Because UV radiation is known to cause
      excessive generations of reactive oxygen species (ROS) which in turn results in a
      situation known as oxidative stress, the approaches aimed at counteracting ROS
      production may be useful for the prevention of skin cancer. One approach to
      reduce its occurrence is through 'photochemoprotection', which we define as 'the
      use of agents capable of ameliorating the adverse effects of UVB on the skin'.
      Among many photochemoprotective agents, botanical antioxidants are showing
      promise. This review focuses on photochemopreventive effects of selected
      botanical antioxidants. We suggest that the use of botanical antioxidants in
      combination with the use of sunscreens and educational efforts to avoid excessive
      sun exposure may be an effective strategy for reducing incidence of skin cancer
      and other UV-mediated damages in humans.

PMID- 12239424
TI  - Photoprotection of UV-irradiated human skin: an antioxidative combination of
      vitamins E and C, carotenoids, selenium and proanthocyanidins.
AB  - Endogenous antioxidants are decreased in skin and blood during UV exposure.
      Combined supplementation of beta-carotene, alpha-tocopherol and ascorbic acid in
      addition to topical sunscreens may help to lower the risk of sunburning. Acute UV
      erythema with sunburn reaction are the most important factors in conjunction with
      the cumulative life-long UV dose for inducing skin damage resulting in
      photoageing and precancerous and cancerous lesions. Therefore, a clinical,
      randomized, double-blind, parallel group, placebo-controlled study was conducted
      in healthy young female volunteers (skin type II) investigating the preventive,
      photoprotective effect of supplementation with Seresis, an antioxidative
      combination containing both lipid and water-soluble compounds: carotenoids (beta
      carotene and lycopene), vitamins C and E, selenium and proanthocyanidins. In this
      study, the oral administration of Seresis appeared to be well tolerated. The
      preparation contains antioxidant compounds in quantities occurring at
      physiological levels and can therefore be used safely over a long period of time.
      Despite the fact that the assessment of the light sensitivity (minimal erythemal
      dose, chromametry) of the skin did not show any statistically significant
      differences between the Seresis and the placebo group, a clear statistical trend,
      however, could be demonstrated, i.e. Seresis was able to slow down the time of
      the development and grade of UVB-induced erythema. The primary efficacy parameter
      matrix metalloproteinases 1 (MMP-1) between treatment and placebo group following
      UV irradiation showed a significant difference (p < 0.05), which occurred due to
      the fact that after a 2-week UV irradiation, MMP-1 slightly increased (p < 0.03)
      in the placebo group and decreased (p < 0.044) in the treated group. The MMP-9
      changes showed a clear tendency of decrease in the Seresis group (p < 1.393) and
      increase (p < 0.048) in the placebo group. These data emphasise that
      supplementation with Seresis decreases the UV-induced expression of MMP-1 and 9,
      which might be important in photoprotective processes. From our data, we thus
      finally draw the conclusion that by the combination of antioxidants, such as in
      the formulation of Seresis, a selective protection of the skin against
      irradiation can be achieved. This might be important for future recommendations
      for immediate suppression of the early phase of UV-induced erythema, that means
      pharmacological prevention of sunburn reaction as well as subsequent chronic skin
      damage.

PMID- 12239425
TI  - Photocarcinogenesis: UVA vs. UVB radiation.
AB  - Recent research is revealing combinations of disturbed oncogenic and tumor
      suppressive signaling pathways by altered or missing genes in skin cancers:
      mutated PTCH (in the mitogenic Sonic Hedgehog pathway) and mutated p53 tumor
      suppressor gene in basal cell carcinomas (BCC), possibly an activated mitogenic
      RAS pathway and mutated p53 in squamous cell carcinomas (SCC), and possibly an
      activated MET/RAS pathway and inactive p16(INK4a) tumor suppressor in cutaneous
      melanomas. UV radiation damages DNA and can give rise to genomic alterations,
      varying from point mutations to crude chromosomal dislocations. UVB radiation
      (wavelength band 280-315 nm) is more carcinogenic than UVA radiation (315-400 nm)
      in experimental induction of SCC. The impact of UVB radiation can be clearly
      inferred from the characteristic point mutations in p53 found in human SCC and
      BCC. In contrast to UVB radiation, much of the mutagenic and carcinogenic action
      of UVA radiation appears to be mediated through reactive oxygen species (ROS).
      Experiments have shown that UVA1 (340-400 nm) exposure induces SCC largely
      without the characteristic point mutations in p53. Both UVB and UVA radiation can
      give rise to ROS-related point mutations (e.g. G to T) and crude genomic
      alterations (e.g. deletions) which may not be recognized as caused by UV
      radiation.

PMID- 12239426
TI  - The role of nuclear factor-kappa B and melanogenesis in tumor necrosis factor
      alpha-induced apoptosis of normal human melanocytes.
AB  - The proapoptotic potential of tumor necrosis factor-alpha (TNF-alpha) has been
      demonstrated for various cell types, whereas nuclear factor-kappaB (NF-kappaB) is
      known to support the transcription of prosurvival genes. In the present study,
      investigation of normal human melanocytes revealed induction of apoptosis after
      TNF-alpha treatment (100 U/ml) in only 3 out of 11 cultures analyzed, whereas 8
      cultures remained largely resistant. In sensitive cultures, NF-kappaB binding
      activity was found increased after TNF-alpha treatment; apoptosis-resistant cells
      were characterized by relatively high basic NF-kappaB binding activities and did
      not show NF-kappaB activation after TNF-alpha treatment. Inhibition of NF-kappaB
      by a specific inhibitor, Bay-11, either induced apoptosis itself or resistant
      melanocyte cultures became sensitive to TNF-alpha treatment. No correlation was
      found between apoptosis sensitivity and the expression of TNF receptor-1 or the
      expression of Bax, Bcl-2 and Bcl-X(L). A strong correlation, however, was found
      regarding the pigmentation degree, as high pigmentation correlated with apoptosis
      resistance and sensitive melanocyte cultures were weakly pigmented. These data
      may indicate that in cultured melanocytes, high levels of melanogenesis lead to
      an increase in oxidative stress which itself causes NF-kappaB activation. NF
      kappaB mediates the transcription of antiapoptotic factors which may block TNF
      alpha-induced apoptosis at early steps of the signal cascade.

PMID- 12239427
TI  - UVB-irradiated dendritic cells induce nonproliferating, regulatory type T cells.
AB  - It is well established that low-dose UVB radiation inhibits the antigen
      presenting cell (APC) function of murine Langerhans cells in vivo and converts
      them from immunogenic to tolerogenic APC. Recently, we have shown that UVB
      irradiated murine bone marrow-derived dendritic cells (UVB-DC) suppressed
      proliferation of naive and primed T cells, but tolerized primed T cells only. To
      examine the underlying mechanism for these differences, naive OVA(323-339)
      peptide-specific, TCR-transgenic T cells from DO11.10 mice were analyzed
      following coculture with unirradiated DC or UVB-DC. First, we found that UVB-DC
      inhibit OVA-specific T cell proliferation UVB dose and antigen dose dependently.
      Analysis of T cells cocultured with both, unirradiated and UVB-DC, revealed an
      activated T cell phenotype with increased expression of CD25 and CD69 by FACS.
      Supernatants harvested from cocultures with UVB-DC showed reduced levels of IFN
      gamma, IL-2 and IL-4, but not TGF-beta, compared with unirradiated DC as
      determined by ELISA. Furthermore, these T cells did not proliferate upon
      restimulation. Interestingly, addition of these nonproliferating T cells to
      cocultures of naive T cells and freshly prepared unirradiated DC inhibited T cell
      proliferation depending on the number of added nonproliferating T cells. Also, in
      supernatants, increased levels of TGF-beta were found. Therefore, our data
      indicate that UVB-DC propagate T cells with a regulatory function. Since
      regulatory T cells are characterized by enhanced TGF-beta secretion and increased
      CTLA-4 expression, we currently investigate the role of CTLA-4 phenotypically and
      functionally. In conclusion, we have shown that UVB-DC inhibit proliferation of
      naive OVA-specific T cells. These T cells, exhibiting an activated phenotype and
      increased TGF-beta production, suppress proliferation of naive T cells cocultured
      with unirradiated DC. These results suggest that UVB-DC induce nonproliferating,
      regulatory type T cells.

PMID- 12239428
TI  - Trioxsalen in the presence of UVA is able to induce nuclear factor kappa B
      binding activity in HaCaT keratinocytes.
AB  - It has been described that treatment of cells with high dose psoralen and UVA
      induce the production of reactive oxygen species (ROS) leading to DNA damage.
      Transcription factor nuclear factor kappa B (NFkappaB) plays a crucial role in
      regulating not only cell growth but also cell differentiation, and ROS seem to be
      partly involved in these mechanisms. The aim of this research was to find out the
      effect of a combined treatment with trioxsalen (TMP)/UVA on NFkappaB binding
      activity in HaCaT keratinocytes. HaCaT keratinocytes were treated with 27
      microg/l TMP. This concentration did not affect the proliferation rates, nor was
      it toxic, as shown by cytotoxicity assays. After treatment with TMP with or
      without UVA (1 J/cm(2)), NFkappaB binding activity in nuclear protein extracts
      was measured by electrophoretic mobility shift assays. The effect on cytokines
      and cytokine receptor genes was investigated using cDNA expression arrays. An
      inhibitory effect on NFkappaB binding activity was found between 30 and 60 min
      after TMP supplementation of the culture media. UVA irradiation induced a 2-fold
      increase in NFkappaB binding activity in TMP supplemented HaCaT keratinocytes
      compared with the non-irradiated control. In addition, NFkappaB binding activity
      was higher after UVA irradiation with TMP than in UVA irradiated cells in the
      absence of TMP. TGF-alpha, IL-1R, IL-2Ralpha, IL-12beta and PDGF expression was
      induced by UVA. However, all of them except PDGF were inhibited by combined
      TMP/UVA treatment. Using an inhibitor of NFkappaB activation, we found out that
      under these conditions, these cytokines or cytokine receptor genes are apparently
      not regulated by NFkappaB. Our results indicate that a combined TMP/UVA treatment
      of HaCaT keratinocytes induces NFkappaB binding activity, and that this is a
      synergistic effect. The investigated cytokines, and cytokine receptor genes do
      not seem to be NFkappaB regulated; however, TMP shows anti-inflammatory
      capacities in vitro.

PMID- 12239429
TI  - Molecular mechanisms involved in UV-induced apoptotic cell death.
AB  - Ultraviolet radiation (UV) induces a variety of biological effects which include
      the induction of programmed cell death. UV-induced apoptosis seems to represent a
      controlled scavenging mechanism which protects cells from malignant
      transformation in human skin. To exert these effects on a cellular base, UV uses
      a variety of signaling pathways, involving nuclear DNA damage as a predominant
      pathway, since experimental reduction of DNA damage is associated with a loss of
      these effects. On the other hand, UV has been found to utilize extranuclear
      components located in the cytoplasm or at the cell membrane for signaling. UV can
      directly activate cell surface death receptors, thereby triggering the apoptotic
      machinery. Oxidative stress accompanied by mitochondrial changes and cytochrome c
      release are further involved in UV-mediated apoptosis. The following review will
      briefly discuss current aspects of the interplay between the different signaling
      pathways involved in UV-induced apoptosis.

PMID- 12239430
TI  - Pro- and anti-apoptotic effects of nitric oxide in irradiated keratinocytes: the
      role of superoxide.
AB  - Ultraviolet radiation (UV) induces apoptosis in keratinocytes by both p53- and
      death receptor-dependent pathways. It also generates free radicals in
      keratinocytes, including the synthesis of nitric oxide (NO) by constitutive and
      inducible NO synthases (NOS). NO has both pro- and anti-apoptotic effects. We
      wished to determine which of these was predominant in keratinocytes. Human
      CCD1106 keratinocytes were irradiated with UVB in the presence and absence of
      several NOS antagonists. Apoptosis was measured by flow cytometry with annexin V
      binding. NOS antagonism consistently altered UVB-induced apoptosis measured 18 h
      after irradiation. In 9 of 13 experiments, NOS antagonism increased apoptosis.
      However, in 4 of 13 experiments, NOS antagonism reduced apoptosis. We postulated
      that the variable effects of NO might be due to a critical balance between UVB
      induced NO and superoxide production. We predicted that NO would be anti
      apoptotic in the presence of low O(-)(2), but pro-apoptotic when NO combined with
      O(-)(2) to form peroxynitrite. Though superoxide dismutase reduced apoptosis
      after UVB, addition of peroxynitrite did not affect apoptosis. We conclude that
      NO released by UV irradiation is anti-apoptotic; however, the levels of O(-)(2)
      may be a determinant of NO action.

PMID- 12239431
TI  - Effects of UVA and L-ascorbic acid on nuclear factor-kappa B in melanocytes and
      in HaCaT keratinocytes.
AB  - Nuclear factor-kappaB (NFkappaB) is a pleiotropic transcriptional activator,
      which is a sensitive transcriptional factor for free radicals and activates
      multiple target genes. UVA is very efficient in inducing free radicals in human
      skin cells. L-ascorbic acid is regarded as a scavenger of UVA-induced free
      radicals in human keratinocytes. In epidermis, melanocytes and keratinocytes play
      an important protective role against skin photodamage. In the present study, we
      aimed to investigate the role of NFkappaB on photodamage in melanocytes and
      keratinocytes. Normal human melanocytes (NHM) and HaCaT keratinocytes were
      treated with UVA (500 mJ/cm(2), 1,000 mJ/cm(2)) and/or L-ascorbic acid (100
      microM, 250 microM). NFkappaB binding activity was analysed by electrophoretic
      mobility shift assay. NFkappaB binding activity was increased by UVA irradiation
      in HaCaT keratinocytes, but it was not affected in NHM. On the other hand, L
      ascorbic acid decreased NFkappaB binding activity both in UVA-irradiated and in
      non-irradiated NHM. In contrast, NFkappaB binding activity in HaCaT keratinocytes
      was increased after treatment with L-ascorbic acid. In addition, L-ascorbic acid
      synergistically induced NFkappaB binding activity with UVA irradiation. The
      contrary response on NFkappaB binding activity in NHM and HaCaT keratinocytes
      indicated that the redox regulation might be different on photoprotective action
      in melanocytes and keratinocytes.

PMID- 12239432
TI  - Beta-carotene plasma levels and content in oral mucosal epithelium is skin type
      associated.
AB  - Beta-carotene is one of the important antioxidants in the defence mechanisms of
      the body against reactive oxygen species and, in particular, against UV radiation
      in the skin. The aim of our study was to measure if differences of beta-carotene
      in the peripheral blood and oral mucosa exist in relation to skin types I-IV
      (according to Fitzpatrick). One hundred and seventy-four subjects were studied
      with regard to beta-carotene plasma levels. Out of these, 63 healthy volunteers
      (24-28 years) with skin type I-IV were studied with regard to plasma levels and
      content of beta-carotene in the oral mucosa. Ten millilitres of venous blood was
      obtained and oral mucosa cells (OMCs) were taken by gently brushing the oral
      cavity without contamination of capillary leak blood. A modified method by Stich
      et al. was used for preparing cells and measuring beta-carotene in OMCs by HPLC.
      Plasma levels of skin type I were 0.1565 micromol/l and increased via skin types
      II with 0.2989 and III with 0.5457 to 1.221 micromol/l in skin type IV. A similar
      skin type-dependent increase in beta-carotene could be measured in the oral
      mucosa epithelium (OMC) either when measured in micromoles/litre (0.0056-0.0217)
      or in nanograms/10(6) cells (0.2090-0.9989). Smokers had significantly lower
      levels of beta-carotene in plasma and OMC as compared with non-smokers. Non
      melanoma and melanoma skin cancer patients also showed lower beta-carotene plasma
      levels and in the OMCs as well. From our results, we conclude that plasma levels
      and content of beta-carotene in the cytoplasm of OMCs show marked and significant
      differences with regard to skin types I-IV. The question arises whether these
      differences are genetically controlled.

PMID- 12239433
TI  - Melatonin suppresses reactive oxygen species in UV-irradiated leukocytes more
      than vitamin C and trolox.
AB  - To prove the relative potency of melatonin as a radical scavenger in UV
      irradiated leukocytes, it was compared to other antioxidative substances such as
      trolox and vitamin C. Human leukocytes were isolated from EDTA whole blood and
      incubated with melatonin, trolox and vitamin C. The experiments were performed in
      a wide concentration range from 0.1 nM to 1 mM and in a small concentration range
      from 0.5 to 2 mM (mel), 5 mM (trolox) and 10 mM (vit. C). Irradiation was
      performed with UV-light (280-360 nm) at a dose of 750 mJ/cm(2). Radical formation
      was measured by the chemiluminescence technique. The maximum effect of radical
      suppression was seen at a concentration of 10 nM (p = 0.003) and 1 mM melatonin
      (p < 0.001) and vitamin C (p = 0.002; p < 0.001), respectively. ROS suppression
      by trolox was only significant at 1 mM (p < 0.001). In the small concentration
      range, a linear dose-response relationship was found and melatonin showed the
      strongest radical suppression (IC(50) = 0.21 mM) followed by vitamin C (IC(50) =
      0.26 mM) and trolox (IC(50) = 1.03 mM).

PMID- 12239434
TI  - Emblica cascading antioxidant: a novel natural skin care ingredient.
AB  - A standardized extract of Phyllanthus emblica (trade named Emblica) was found to
      have a long-lasting and broad-spectrum antioxidant activity. The product has no
      pro-oxidation activity induced by iron and/or copper because of its iron and
      copper chelating ability. Emblica helps protect the skin from the damaging
      effects of free radicals, non-radicals and transition metal-induced oxidative
      stress. Emblica is suitable for use in anti-aging, sunscreen and general purpose
      skin care products.

PMID- 12239435
TI  - Electron spin resonance detection of UVA-induced free radicals.
AB  - Free radicals generated during UV irradiation of human skin biopsies were
      measured with electron spin resonance spectroscopy by using spin traps. The
      generation of hydroxyl and lipid radicals in skin is mainly caused by the UVA
      part of the solar spectrum.

PMID- 12239436
TI  - Comorbidity of anxiety disorder among patients with bipolar I disorder in
      remission.
AB  - The aim of this study was to assess the comorbidity of lifetime and current
      prevalences of anxiety disorders among 70 patients with bipolar I disorder in
      remission using structured diagnostic interviews and to examine the association
      between comorbidity and several demographic and clinical variables. Forty-three
      (61.4%) bipolar I patients also met DSM-IV criteria for at least one lifetime
      comorbid anxiety disorder. Obsessive-compulsive disorder (39%) was the most
      common comorbid lifetime anxiety disorder, followed by simple phobia (26%) and
      social phobia (20%). First episode and male sex were found to have lower rates of
      comorbid current anxiety disorders. The presence of anxiety disorders was related
      to significantly higher scores on both anxiety and general psychopathology
      scales. The results of the present study support previous findings of a high
      comorbidity rate of anxiety disorders in bipolar I disorder cases and indicate
      that the presence of an anxiety disorder leads to more severe psychopathology
      levels in bipolar I patients.

PMID- 12239437
TI  - Family history, life events and the factorial structure of depression in a
      Nigerian sample of inpatients.
AB  - The aims of the study were to examine the frequency of a family history of
      depression among 96 patients with subtypes of ICD-10 depression, their life event
      scores, and compare the factors of depression with other studies. Subjects were
      assessed using the PSE-9, 23-item HDRS, BPRS and life event schedule. Family
      history was significantly commoner for psychotic depression. There were no
      significant differences in life event scores. The HDRS factors -- core
      depression, endogenous, insomnia and psychic anxiety -- were similar to those of
      previous studies. Combining the HDRS and BPRS yielded factors that were more
      representative of the dimensions of depression. While family history
      distinguishes psychotic depression, life events are important with increasing
      age, but require interaction with predisposing factors. Although depression is
      heterogeneous, there are core clinical features which are stable across cultures
      and time. Family history is more associated with the severer forms of the
      disorder, and combining relevant questionnaires maybe more useful in research on
      symptom profiles.

PMID- 12239438
TI  - Linguistic analysis of the speech output of schizophrenic, bipolar, and
      depressive patients.
AB  - Using speech samples of 100 patients suffering from schizophrenia, bipolar
      illness and major depression, we addressed the question of the extent to which
      the linguistic abnormalities in the speech of these patients represent diagnosis
      specific characteristics or constitute independent, syndrome-like dimensions of
      the illnesses. All speech samples were transcribed by a professional linguist who
      was blind to both identity and diagnosis of the patients. The majority of the
      deviant linguistic variables was found to be common to all three diagnostic
      groups under comparison, while only a few linguistic variables exhibited
      statistically significant between-group differences. On the other hand, when the
      respective variables were analysed as a multivariate entity, the variety of
      subtle between-group differences allowed us to discriminate between the
      diagnostic groups at an overall performance of 72.7% correctly classified
      patients. There was an almost complete lack of association between linguistic
      abnormalities and psychopathology syndromes. In particular, we found no
      correlation between the syndrome 'formal thought disorder' and the large variety
      of linguistic variables used in this investigation. In consequence, we conjecture
      that linguistically deviant speech characteristics represent an independent
      syndrome complex manifested at varying intensities across mental illnesses, and
      that this syndrome complex deserves greater attention, not only with respect to
      the principal understanding of the underlying disturbances, but also as a
      potential target of therapeutical intervention.

PMID- 12239439
TI  - Replication of a two-factor model of the Beck Depression Inventory in alcohol
      dependents and suicide attempters.
AB  - The factor structure of the Beck Depression Inventory (BDI) is still
      controversial. The present study attempted to replicate a general two-factor
      model (cognitive-affective and somatic factors) of the BDI with a confirmatory
      Procrustes rotation procedure in two clinical samples of patients being treated
      for alcohol dependence (N(1) = 243, N(2) = 148) and one clinical sample of
      patients admitted to an acute psychiatric ward because of an act of deliberate
      self-harm (N(3) = 144). In addition, due to the neglect of gender-specific
      analysis in factor-analytic studies of the BDI, the two-factor model was tested
      for males and females separately. The results did not support the validity of the
      two-factor model in the total samples. Gender-specific findings indicated a
      better fit of the model in male samples. Possible implications of a gender
      specific factor structure of the BDI are discussed.

PMID- 12239440
TI  - Mood changes following acute tryptophan depletion in healthy adults.
AB  - A decrease in central serotonergic activity following plasma tryptophan depletion
      has been shown to provoke a deterioration of mood. We studied the impact of sex
      and aggressive traits on mood changes following tryptophan depletion in healthy
      volunteers. Twelve healthy subjects (6 males, 6 females, 24-31 years), who were
      screened for psychiatric and non-psychiatric medical illness, were administered a
      tryptophan-depleting amino acid mixture (TD) and a placebo mixture on two
      different occasions in a double-blind crossover design. Psychometric measures
      included the preliminary determination of aggressive traits and depression and
      repeated assessments of mood and emotionality. The tryptophan-free amino acid
      mixture caused a marked depletion of plasma tryptophan with lowest levels
      occurring between 3 and 5 h after TD. Maximum changes in mood occurred about 10 h
      after TD, but only in high-aggressive women who scored significantly higher in
      arousal, anger and depressed mood, whereas low-aggressive women and men did not
      show any effect of TD. In addition, we could not confirm an increase in
      aggressive mood (anger) after TD in males with higher scores of trait aggression,
      presumably because the level of trait aggression was not high enough in this
      group. Due to the small sample size, our results that tryptophan depletion exerts
      a rapid mood-lowering effect on healthy women with pre-existing aggressive traits
      can only be seen as preliminary and have to be confirmed in further studies with
      larger samples.

PMID- 12239441
TI  - Psychophysiological correlates of peritraumatic dissociative responses in
      survivors of life-threatening cardiac events.
AB  - The psychophysiological startle response pattern associated with peritraumatic
      dissociation (DISS) was studied in 103 survivors of a life-threatening cardiac
      event (mean age 61.0 years, SD 13.95). Mean time period since the cardiac event
      was 37 (79 IQD) months. All patients underwent a psychodiagnostic evaluation
      (including the Peritraumatic Dissociative Experiences Questionnaire) and a
      psychophysiological startle experience which comprised the delivery of 15
      acoustic startle trials. Magnitude and habituation to trials were measured by
      means of electromyogram (EMG) and skin conductance responses (SCR). Thirty-two
      (31%) subjects were indexed as patients with a clinically significant level of
      DISS symptoms. High-level DISS was associated with a higher magnitude of SCR
      (ANOVA for repeated measures p = 0.017) and EMG (p = 0.055) and an impaired
      habituation (SCR slope p = 0.064; EMG slope p = 0.005) in comparison to subjects
      with no or low DISS. In a subgroup analysis, high-level DISS patients with severe
      post-traumatic stress disorder (PTSD; n = 11) in comparison to high-level DISS
      patients without subsequent PTSD (n = 19) exhibited higher EMG amplitudes during
      all trials (repeated measures analysis of variance F = 5.511, p = 0.026). The
      results demonstrate exaggerated startle responses in SCR and EMG measures - an
      abnormal defensive response to high-intensity stimuli which indicates a steady
      state of increased arousal. DISS patients without PTSD exhibited balanced
      autonomic responses to the startle trials. DISS may, therefore, unfold malignant
      properties only in combination with persistent physiological hyperarousability.

PMID- 12239442
TI  - Comorbidity of dependent personality disorder and separation anxiety disorder in
      addictive disorders and in healthy subjects.
AB  - The aim of the study was to determine the comorbidity of dependent personality
      disorder (DPD) and separation anxiety disorder (SAD) in large nonclinical and
      clinical samples. Using a cross-sectional method, the relationship between these
      disorders was studied in 784 healthy subjects and in 708 subjects presenting with
      various addictive behaviors. DPD was significantly associated with SAD in healthy
      subjects, alcoholics, drug abusers and anorectic and bulimic patients. The
      comorbidities of SAD and DPD suggest that specific therapeutic strategies could
      be discussed. Moreover, longitudinal studies are required to determine if SAD
      constitutes a risk factor for DPD.

PMID- 12239443
TI  - Personality traits in migraine and tension-type headaches: a five-factor model
      study.
AB  - Although abnormal personality traits have been frequently reported in patients
      with primary headaches, the overlaps between these domains need a clear standard
      definition, for example, by a five-factor personality model. Moreover,
      personality abnormalities in patients with episodic tension-type headache (ETH)
      and migraine with aura (MA) are less well studied. Therefore, we administered
      Zuckerman-Kuhlman's Personality Questionnaire to 72 patients suffering from
      chronic tension-type headaches (CTH), 33 with ETH, 15 with MA and 57 with
      migraine without aura (MO), as well as 58 healthy subjects. Depressive trends
      were measured with Plutchik-van Praag's Depression Inventory. Compared to healthy
      controls, the CTH, ETH and MO groups showed significantly greater neuroticism
      anxiety and depression. In addition, the MO group scored significantly higher on
      aggression-hostility than healthy controls. No abnormal personality traits were
      found in patients with MA. This study, from the perspective of a five-factor
      model, confirms most previous reports about personality in patients with primary
      headaches and establishes elevated aggression-hostility only in MO sufferers.

PMID- 12239444
TI  - Small cell lung cancer: defining a role for emerging platinum drugs.
AB  - Small cell lung cancer (SCLC) is characterized by early dissemination and a
      rapid, aggressive clinical course. It has, however, marked susceptibility to both
      chemotherapy and radiotherapy, although treatment is complicated by the fact that
      SCLC tumors invariably develop resistance to multiple chemotherapeutic agents.
      Local therapy is rarely of benefit in SCLC because three-quarters of patients
      present with metastatic disease and many of the remaining patients are thought to
      have micrometastatic disease. Chemotherapy is, therefore, the cornerstone of
      treatment. Of the many combination regimens used, etoposide/cisplatin or
      etoposide/carboplatin have emerged as the regimens of choice because they offer a
      good therapeutic index and can be combined with radiotherapy. Response to second
      line therapy remains consistently poor. As the prototype platinum compound,
      cisplatin has played a major role in the management of SCLC. Although its exact
      contribution to the treatment of SCLC has been difficult to ascertain, a recent
      meta-analysis reported a significant 1-year survival advantage of approximately
      4% with cisplatin-containing regimens versus regimens without. However, cisplatin
      is characterized by several serious adverse events and, like other
      chemotherapeutic agents, is eventually rendered ineffective against SCLC because
      of acquired resistance. Several new platinum formulations or compounds are
      showing promising activity in SCLC. The impetus for their development has been to
      circumvent cisplatin resistance or to improve upon the toxicity profile of
      cisplatin. If the early promise shown by these compounds is confirmed in the
      clinic, they may offer a new approach to the treatment of SCLC, including
      recurrent disease for which limited treatment options are currently available.

PMID- 12239445
TI  - Phase II trial of vinorelbine, cisplatin and continuous infusion of 5
      fluorouracil followed by hyperfractionated radiotherapy in locally advanced head
      and neck cancer.
AB  - OBJECTIVE: We undertook a prospective phase II study to assess the feasibility
      and activity of a new induction chemotherapy regimen followed by
      hyperfractionated irradiation in locally advanced squamous cell head and neck
      cancer. METHODS: 25 patients with locally advanced head and neck cancer were
      treated with 4 cycles of vinorelbine (20 mg i.v. day 1, 3), cisplatin (60 mg/m(2)
      i.v. day 1) and 5-fluorouracil (200 mg/m(2) continuous i.v. infusion day 1-21)
      (ViFuP regimen) followed by bifractionated radiotherapy (bidRT) up to 74.4 Gy in
      62 fractions of 1.2 Gy twice daily. RESULTS: Chemotherapy was well tolerated, 6
      patients developed grade 3 and one patient grade 4 neutropenia. Response to
      chemotherapy was observed in 19 patients (76%) including three complete responses
      and 16 partial responses. Planned bidRT was completed in 25 patients and all but
      one received planned bidRT dose without interruptions. Radiotherapy was well
      tolerated, mucositis was the most common side effect (grade 3-12 patients, grade
      4-1 patient). At evaluation after the completion of bidRT, 13 patients had
      complete response (52%), 7 partial response (28%), 2 stable disease and 3 tumor
      progression. At the median follow-up of 18.2 months, 11 patients were alive and
      free of disease, and 14 patients had died (12 of tumor). Late xerostomy was
      observed in all but one 3-month survivors. Late mandibular necrosis was seen in 1
      patient. CONCLUSIONS: bidRT preceded by ViFuP seems a feasible and active
      combination in locally advanced head and neck cancer. Good patient compliance did
      not compromise the delivery of planned dose of bidRT. However, short median
      duration of response (14.6 months) and moderate median overall survival (18.7
      months) indicate the need for more intensive therapeutic strategies. On the basis
      of these results, modifications of our treatment schedule (shortening the overall
      treatment time by reduction of chemotherapy cycles and the use of chemotherapy
      concomitantly with irradiation) are planned for the future study.

PMID- 12239446
TI  - Prognostic factors of secondary ovarian carcinoma.
AB  - OBJECTIVE: Although the ovaries are common sites of metastases from a variety of
      primary neoplasms excluding carcinomas of the genital tract, there were few
      reports concerning survival and prognostic factors. The objective of this study
      was to assess the clinical factors affecting survival. METHODS: Fifty-three
      secondary ovarian carcinomas excluding metastases from genital tract carcinoma
      were registered by the Tokai Ovarian Tumor Study Group from 1989 to 1999. FIGO
      staging was set without considering the pathologic findings of the lymph nodes
      and the primary tumors. RESULTS: Twenty-four patients were stage I, 11 were stage
      II, 16 were stage III, and 2 were stage IV. There were significant differences in
      the survival curves between the early stages (I and II) and advanced stages (III
      and IV). The 5-year survival rate for patients without residual tumors was 39.9%,
      while all patients with residual tumors after surgery died within 33 months. The
      most frequent primary tumor was large intestinal carcinoma, and the second was
      gastric carcinoma. The 5-year survival rate for patients with large intestinal
      primary tumors was significantly better than that with stomach tumors.
      Multivariate analysis demonstrated that tumor stage and primary tumor sites were
      significant prognostic factors. CONCLUSION: FIGO staging without considering
      lymph node involvement and the primary tumor was a significant prognostic factor,
      and prognostic factors for primary ovarian carcinomas can be applied to secondary
      ovarian carcinomas. Furthermore, the primary tumor site was also an important
      prognostic factor for survival.

PMID- 12239447
TI  - Vinblastine and interferon-gamma combination with and without 13-cis retinoic
      acid for patients with advanced renal cell carcinoma. Results of two phase II
      clinical trials.
AB  - BACKGROUND: The aim of this study is firstly to determine the response rates and
      toxicity of two regimens containing vinblastine (VBL) in combination with
      interferon-gamma (IFN-gamma) in the treatment of patients with advanced renal
      cell carcinoma (RCC), and secondly to evaluate the additional efficacy of 13-cis
      retinoic acid (13-CRA) in RCC. METHODS: Twenty-nine patients were included in the
      first trial (Trial 1) and 40 in the second one (Trial 2). The therapy given in
      Trial 1 consisted of VBL 0.15 mg/kg i.v. every 2 weeks and IFN-gamma 100 microg
      s.c. 3 times weekly. In Trial 2, the therapy consisted of the same two drugs, in
      the same doses, plus oral 13-CRA 40 mg/day. RESULTS: In Trial 1 there were 3
      (10.3%) patients with complete response, 3 (10.3%) patients with partial
      response, 8 (27.6%) patients with stable disease and 15 (51.7%) patients with
      progressive disease. In Trial 2, there was no complete response, however, 3
      (7.5%) patients had partial response. Additionally, 15 (37.5%) patients
      maintained stable disease and 14 (35%) patients had progressive disease. In Trial
      1, the median survival was 12.56 months (95% CI, 6.8-18.3, range 0.59-42.49) and
      the median time to progression was 3.21 months (95% CI, 1.7-4.7, range 0.03
      42.49). In Trial 2, the median survival was 9.54 months (95% CI, 5.9-13.1, range
      0.43-24.1) and the median time to progression was 3.9 months (95% CI, 0.8-7,
      range 0.26-24.1). In Trial 1, granulocytopenia grade 3 and 4 appeared in 5
      (17.2%) patients and anaemia grade 3 in 1 (3.4%) patient. In Trial 2, there were
      grade 3 toxicities, as granulocytopenia in 5 (12.5%) patients, anemia in 4
      (10.0%) patients, stomatitis in 3 (7.5%) patients, fatigue/malaise in 3 (7.5%)
      patients and 1 (2.5%) had diarrhea. No toxic deaths occurred in both studies.
      CONCLUSION: The use of IFN-gamma does not enhance the low response of VBL-based
      chemotherapy. The additional administration of 13-CRA with the combination of VBL
      and IFN-gamma does not add to the efficacy of this combination in patients with
      advanced renal cell carcinoma. New active agents are needed to treat patients
      with this disease.

PMID- 12239448
TI  - Stepwise hook extension technique for radiofrequency ablation therapy of
      hepatocellular carcinoma.
AB  - OBJECTIVE: Our study was designed to examine the efficacy of stepwise hook
      extension technique for radiofrequency ablation (RFA) therapy of hepatocellular
      carcinoma in a randomized controlled study. METHOD: Twenty patients with
      hepatocellular carcinoma measuring <25 mm were divided randomly into two equal
      groups. RFA was applied using our new stepwise hook extension technique in
      patients of group 1, and the full extension method in group 2. The 10-hook
      electrode of LeVeen needle was deployed in four steps to full extension during
      ablation in group 1, and full extension at start of treatment in group 2.
      RESULTS: Roll-off was achieved in all 10 patients of group 1, indicative of
      sufficient tumor coagulation, but only in 3 of 10 patients of group 2. The median
      time to completion of treatment was 6 min and 55 s (range 3 min to 14 min and 3
      s) and 15 min (6-15 min), respectively. The total power output used for RF was
      lower in group 1 than in group 2 (median 271 vs. 1,045 W.m). The diameters of RFA
      induced lesions were not significantly different between the groups (group 1: 27,
      range 23-37 mm; group 2: 23, 0-42 mm). CONCLUSIONS: Application of RFA using
      stepwise hook extension technique is superior to the full extension method since
      it produces the same therapeutic effects within a short period using a lower
      energy.

PMID- 12239449
TI  - Phase II study with docetaxel and cisplatin in the treatment of recurrent and/or
      metastatic squamous cell carcinoma of the head and neck.
AB  - PURPOSE: Since the combination of cisplatin and docetaxel have demonstrated
      activity in squamous cell carcinomas of the lung and oesophagus before, promising
      results in recurrent metastatic head and neck cancer were expected. PATIENTS AND
      METHODS: Between September 1998 and October 2000, 40 patients entered this trial,
      38 of whom were evaluable. Six patients were previously untreated, 24 had surgery
      and/or radiotherapy and 13 had received chemoradiation and/or surgery. Therapy
      consisted of 75 mg/m(2) docetaxel (1-hour infusion) and 75 mg/m(2) cisplatin (90
      min infusion) on day 1, repeated every three weeks for a maximum of 6 courses.
      All patients received corticosteroids routinely, 5-HT3-antagonists, and
      hydration. RESULTS: The overall response rate was 52.5% (95% confidence interval,
      36.1 to 68.5%) including 7 complete (17.5% complete response; CR) and 14 partial
      remissions (35% partial response; PR). The overall response rate in patients who
      had no prior treatment (n = 6) was 100%, including 3 CR and 3 PR. In patients who
      had prior surgery and/or radiotherapy (n = 21) an overall response rate of 42.8%
      was observed, including 2 CR and 7 PR; 8 patients (38.1%) had stable disease,
      while disease progressed in 3 (14.3%). Six of 13 patients (46.2%) who had prior
      chemoradiation +/- surgery responded, including 2 CR (15.4%) and 4 PR (30.8%), no
      change was seen in 4 patients (30.8%) and tumour progressed in 2 (15.4%). The
      median response duration for all patients was 10 months (range, 3-20), the median
      overall survival was 11 months (range, 1-30). Myelosuppression was commonly
      observed; WHO grade 3 or 4 neutropenia occurred in 12 patients (30%) each, and
      was complicated by septicaemia in 5 cases. WHO grade 3 anaemia was observed in
      only 3 patients (7.5%). Severe non-hematologic toxicity except for alopecia was
      rarely observed, and included diarrhea in 2 (5%), nausea/vomiting in 2 patients
      (5%) and stomatitis in 1 patient (2.5%). CONCLUSION: Our data suggest that
      docetaxel and cisplatin in combination is an effective and fairly well tolerated
      regimen for the treatment of head and neck cancer with an excellent response rate
      in previously untreated patients.

PMID- 12239450
TI  - Nutritional determinants of epithelial ovarian cancer risk: a case-control study
      in Mexico.
AB  - BACKGROUND: Variations in the incidence of cancer can be influenced by diet and
      specific lifestyles. In the last years, diet has been evaluated as an important
      factor in the development of ovarian cancer, even though the results have not
      been consistent. Dietary factors related to the risk of ovarian cancer in Mexican
      women were evaluated. METHODS: A case-control study in Mexico City was done
      during 1995-1997 in a social security hospital, evaluating 84 new cases of
      ovarian cancer and 629 controls. A validated questionnaire with 116 items about
      the frequency and type of food intake was used. The analysis of nutrients was
      done with the residual method adjusted for total energy intake and other
      predictor variables through logistic regression methods. Also, partition models
      estimated the total caloric intake for other sources. RESULTS: The nutrients
      negatively associated with ovarian cancer in the highest versus the lowest
      tertile were retinol (OR 0.52; p for trend = 0.03) and vitamin D (OR 0.43; 95% CI
      0.23-0.80; p = 0.01; residual model). Additionally, carbohydrates were positively
      associated (partition model: OR 1.08; 95% CI 1.00-1.15), and tortilla intake did
      not show an association with ovarian cancer (OR 0.96; 95% CI 0.78-1.17).
      CONCLUSIONS: The diet of the Mexican population is rich in carbohydrates; in
      Mexico corn intake is the main energy source. On the other hand, vitamins such as
      retinol and vitamin D were shown to be associated with this neoplasm in a
      protective way; nevertheless, further studies are necessary to allow us to
      corroborate our results. This is the first attempt in our country that relates
      the Mexican diet to ovarian cancer.

PMID- 12239451
TI  - Increased expression of dipeptidyl peptidase IV in human mesothelial cells by
      malignant ascites from ovarian carcinoma patients.
AB  - Cell surface aminopeptidases play an important role in biological processes
      through degradation of small peptides. There are many bioactive peptides in
      ascites and these peptides are involved in carcinoma cell dissemination and
      infiltration. In human mesothelial cells dipeptidyl peptidase IV (DPPIV) shows
      the highest expression mostly in four cell surface aminopeptidases:
      aminopeptidase A, neutral endopeptidase 24-11, aminopeptidase N and DPPIV. Since
      mesothelial cells are always in contact with ascites, we examined the influence
      of malignant ascites on DPPIV. DPPIV enzyme activity in mesothelial cells was
      enhanced by the addition of ascites obtained from ovarian carcinoma patients in a
      time- and concentration-dependent manner, and flow cytometry and
      immunocytochemistry also revealed an increased expression of DPPIV on the cell
      surface of mesothelial cells. The <3-kD fraction of malignant ascites increased
      the DPPIV enzyme activity to the same level as the total ascites. Northern
      hybridization demonstrated that DPPIV mRNA was increased 3-fold by the addition
      of the <3-kD malignant ascites. In conclusion, DPPIV is highly expressed in human
      mesothelial cells and was regulated by ascites.

PMID- 12239452
TI  - Analysis of losses of heterozygosity of the candidate tumour suppressor gene
      DMBT1 in melanoma resection specimens.
AB  - Deleted in malignant brain tumours 1 (DMBT1), a candidate tumour suppressor gene
      located on chromosome 10q25.3-q26.1, has recently been identified and found to be
      deleted in several different types of human tumours. In melanomas, the
      chromosomal region 10q22-qter is commonly affected by losses, hence we screened
      primary melanoma samples for losses of heterozygosity (LOH), and acquired
      melanocytic naevi and melanomas for transcription of DMBT1 and protein
      expression. Of 38 informative melanomas, 1 nodular melanoma and 2 subcutaneous
      metastases showed LOH of both microsatellites flanking the gene, suggesting loss
      of 1 DMBT1 allele. Three further melanomas showed LOH at 1 informative locus but
      were heterozygous for the second marker. Applying reverse-transcription
      polymerase chain reaction (RT-PCR), DMBT1 transcription was not found in
      melanomas. However, DMBT1 transcription was also absent from the majority of
      naevi from which melanomas frequently arise, making down-regulation of gene
      transcription during transformation from naevus to melanoma unlikely.
      Immunohistochemistry showed nerves, sweat glands and the stratum spinosum of the
      epidermis to be DMBT1 protein positive, whereas the naevi and melanoma cells
      themselves were negative. All considered, the candidate tumour suppressor gene
      DMBT1 does not appear to be a major inactivation target in the development of
      melanomas.

PMID- 12239453
TI  - Predicting chemotherapy response to paclitaxel-based therapy in advanced non
      small-cell lung cancer (stage IIIb or IV) with a higher T stage (> T2).
      Technetium-99m methoxyisobutylisonitrile chest single photon emission computed
      tomography and P-glycoprotein express ion.
AB  - OBJECTIVE: The aim of this study was to compare technetium-99m
      methoxyisobutylisonitrile (Tc-MIBI) chest single photon emission computed
      tomography (SPECT) results, immunohistochemical analyses of P-glycoprotein (Pgp)
      expression and response to paclitaxel in non-small-cell lung cancer (NSCLC).
      METHODS: Before chemotherapy with paclitaxel, 30 patients with stage IIIb or IV
      NSCLC were enrolled in this study. Early chest SPECT was performed 10 min after
      intravenous injection of Tc-MIBI. Tc-MIBI chest SPECT images were qualitatively
      interpreted. Early tumor-to-normal lung ratios (T/NL) were calculated
      quantitatively. Immunohistochemical analyses were performed on multiple
      nonconsecutive sections of the biopsy specimens to determine Pgp expression.
      Chemotherapy response was evaluated in the third month after completion of
      treatment by clinical and radiological methods. RESULTS: All 15 (100%) cases with
      good response and negative Pgp expression had positive results of early Tc-MIBI
      chest SPECT. Ten of 15 (67%) cases with poor response and positive Pgp expression
      had negative results of early Tc-MIBI chest SPECT. These early T/NL ratios (3.3
      +/- 0.8 for the 15 patients with good response and 2.0 +/- 0.2 for the 5 patients
      with poor response) in lung cancer could be detected on early Tc-MIBI chest
      SPECT. The difference was significant (p < 0.05) by an independent Student t
      test. However, no significant differences were found for other prognostic factors
      (age, sex, body weight loss, performance status, tumor cell type, and tumor
      stage) between the good and poor response groups. CONCLUSION: Early Tc-MIBI chest
      SPECT can be used to understand the Pgp expression in NSCLC and to quickly
      predict chemotherapy response to paclitaxel.

PMID- 12239454
TI  - The prognostic value of p27 in gastric cancer.
AB  - OBJECTIVES: p27 is a cyclin-dependent kinase inhibitor and a putative tumor
      suppressor preventing progression of the cell cycle from G1 phase. Recent studies
      have suggested loss of p27 to correlate with poor prognosis in patients with a
      variety of solid tumors. Results in gastric cancer are contradictory. We
      therefore decided to study the potential of p27 as a prognostic marker in a
      consecutively surgically treated, single-institution series of patients. METHODS:
      Using a monoclonal antibody against p27, immunohistochemistry was performed in
      paraffin-embedded tumor specimens from 316 patients. RESULTS: Loss of p27
      immunoreactivity (< or = 5% of the cancer cell nuclei positive) was observed in
      241 (76%) out of 316 stained tumors. We observed no significant correlation
      between the expression of p27 and stage of disease, tumor size, depth of tumor
      invasion, lymph node metastases, distant metastases, Lauren classification,
      Borrmann type, grade of differentiation, age or gender. There was no significant
      difference in gastric cancer specific overall survival between patients with low
      and high p27 expression. CONCLUSION: Our results add further doubt to the
      usefulness of p27 as a prognostic marker in gastric cancer.

PMID- 12239455
TI  - Enhanced expression of thymidylate synthase mediates resistance of uterine
      cervical cancer cells to radiation.
AB  - It has been shown that there is an inverse relationship between the level of
      thymidylate synthase (TS) and therapeutic outcomes in patients with malignancies
      including cervical cancer. To clarify the mechanism of the poor prognosis of
      cervical cancer with high TS expression, we introduced TS cDNA to the human
      uterine cervical cancer cell line SKG-II and evaluated the effect of TS
      expression on its radiosensitivity. After selection, stable transformants of SKG
      II cells expressing high level of TS (SKG-II/TS) and control cells (SKG
      II/luciferase) were obtained. The level of TS measured by the FdUMP-TS binding
      assay was significantly higher (p < 0.05) in SKG-II/TS than in control (2.0 +/-
      0.1 and 1.3 +/- 0.1 pmol/mg, respectively). No difference was observed in in
      vitro cell growth or in vivo tumor growth. On evaluation of in vitro
      radiosensitivity, the 50% growth inhibitory dose (ID(50)) was 3.1 +/- 0.1 Gy in
      SKG-II/TS and was significantly higher (p < 0.01) than that in control (2.2 +/-
      0.1 Gy). From these results, it is suggested that one of the reasons of poor
      outcome of cervical cancer to radiation is high TS expression.

PMID- 12239456
TI  - Expression of S100A6 and S100A4 in matched samples of human colorectal mucosa,
      primary colorectal adenocarcinomas and liver metastases.
AB  - OBJECTIVE: S100A6 and S100A4, two of S100 protein family, have been suggested to
      be associated with cancer tumorigenesis and metastasis. The aim of this study was
      to evaluate the expression levels of S100A6 and S100A4 in matched samples of
      primary human colorectal adenocarcinomas (T), adjacent normal colorectal mucosa
      (N) and liver metastases (M). This gave us the advantage of directly comparing
      levels of S100A6 and S100A4 expression within the same genetic background.
      METHODS: In matched samples of N, T and M from 10 colorectal adenocarcinoma
      patients, expressions of S100A6 and S100A4 were studied by Western blot and
      immunohistochemical analyses using specific antibodies against each protein.
      RESULTS: The expression levels of S100A6 were significantly higher in T than in N
      (p < 0.05), while those of S100A4 showed no difference between T and N. There
      were no significant differences in the expression levels of S100A6 or S100A4
      between M and T. Similar results were obtained by immunohistochemical analysis.
      Moreover, S100A6 was stained more intensely in invading fronts than in central
      portions of both T and M. CONCLUSIONS: The observed differential expression of
      S100A6 and S100A4 suggests that S100A6, rather than S100A4, is associated with
      human colorectal adenocarcinoma tumorigenesis and invasion/metastasis.

PMID- 12239457
TI  - A case of estrogen-producing Brenner tumor with a stromal component as a
      potential source for estrogen.
AB  - BACKGROUND: Although Brenner tumors with endocrine activities have been reported,
      the source or mechanisms for hormone production is poorly known at present. CASE
      REPORT: A 66-year-old Japanese woman presented with atypical vaginal bleeding. A
      left ovarian tumor was detected on ultrasonography and CT scanning. Her serum
      estradiol level was elevated (73.5 pg/ml). We performed total hysterectomy,
      bilateral salpingo-oophorectomy and partial omentectomy. The ovarian tumor was
      diagnosed as a benign Brenner tumor associated with simple hyperplasia of the
      endometrium. Postoperatively, the serum estradiol level decreased.
      Immunoreactivity of cytochrome P-450 aromatase was detected in stromal cells.
      CONCLUSION: Stromal contribution to the secretion of estrogen was shown in this
      case. Considering the known source of estrogen production being tumor cells in
      certain cases of Brenner tumor, there seem to be two types of estrogen-producing
      Brenner tumors depending on the source of estrogen, i.e. tumor cells or stromal
      cells.

PMID- 12239458
TI  - Nitric oxide damage to colonocytes in colitis-by-association: remote transfer of
      nitric oxide to the colon.
AB  - New observations of (1) colitis-by-association, (2) the carriage of nitric oxide
      by haemoglobin, (3) nitric oxide inactivation of CoA, (4) the damage caused to
      colonocytes by a combination of nitric oxide/sulphide/hydrogen peroxide and (5)
      colonic extraction of nitric oxide from the circulation, has led to new views on
      colonocyte damage in colitis. These observations should assist to define
      initiating factors that lead to release of damaging agents (nitric oxide/hydrogen
      peroxide) and to delineate protective mechanisms against colonocyte damage.
      Overall, the production, release, disposal and inactivation of nitric oxide are
      related to damage to colonocytes and consequent ulceration in colitis.

PMID- 12239459
TI  - Comparison of spiral-computed tomography with water-filling of the stomach and
      endosonography for gastric lymphoma of mucosa-associated lymphoid tissue-type.
AB  - BACKGROUND: Endosonography has been reported as the method of choice for local
      staging of patients with gastric lymphoma of mucosa-associated lymphoid tissue
      (MALT)-type. As endosonography is still restricted to specialized centers, we
      have investigated the use of spiral computed tomography of the abdomen with water
      filling of the stomach (hydro-spiral CT) for enhanced contrast in patients with
      gastric lymphoma. PATIENTS AND METHODS: Patients with a histological verified
      diagnosis of gastric lymphoma of MALT-type were included in this prospective
      series. All patients underwent routine staging procedures including
      endosonography of the upper GI-tract carried out by a single individual. In
      addition, patients were subjected to hydro-spiral CT either before or after
      endosonography within a maximal time span of 4 weeks. Results of hydro-spiral CT
      were compared to those of the endosonographic evaluation and histological work-up
      of biopsy specimens. RESULTS: A total of 14 patients with primary gastric
      lymphoma of MALT-type (3 with a high-grade component) were studied prospectively.
      All patients underwent hydro-spiral CT before initiation of treatment, and 2
      patients were also studied following chemotherapy. In the pretherapeutic setting,
      hydro-spiral CT identified gastric lymphoma in 8 patients, while a false negative
      result was seen in 6 patients. In addition, the localization of the lymphoma
      within the stomach was divergent between CT and endosonography in 1 patient. In
      the 2 patients who were also studied after therapy, CT showed unchanged
      thickening of the stomach wall in spite of normalization in the endosonographic
      assessment as well as the histologic evaluation. CONCLUSION: Our results
      demonstrate the superiority of endosonography over hydro-spiral CT for the
      staging and follow-up of patients with gastric lymphoma, who should therefore be
      managed at centers where endosonography is available.

PMID- 12239460
TI  - Antiangiogenic effect of octreotide inhibits the growth of human rectal
      neuroendocrine carcinoma.
AB  - BACKGROUND: Somatostatin and its analogues have antitumor effects on foregut and
      midgut neuroendocrine (NE) tumors, but their effect on hindgut NE tumors is
      unclear. We examined the effect of the somatostatin analogue, octreotide, on
      human rectal NE carcinoma. MATERIALS AND METHODS: Expression of somatostatin
      receptor (sst) on NE carcinoma was examined by immunohistochemical staining.
      Octreotide was added in cell culture medium in order to investigate
      antiproliferative effect toward NE carcinoma in vitro. Octreotide was
      administered for 6 weeks to nude mice xenografted with NE carcinoma. We
      investigated the effect of octreotide on the tumor histologically. The plasma
      levels of VEGF and bFGF were measured. RESULTS: The NE carcinoma and endothelial
      cells expressed sst. Octreotide induced NE carcinoma to apoptosis in vitro and in
      vivo. Octreotide-treated tumors had a massive necrotic area (62.7 +/- 19.3%
      treated vs. 39.7 +/- 20.34% untreated, p < 0.05). Microvessels in the treated
      tumor were decreased (264.0 +/- 48.2/mm(2) treated vs. 341.4 +/- 56.6/mm(2)
      untreated, p < 0.05). The plasma levels of VEGF and bFGF were reduced by
      octreotide. CONCLUSIONS: Octreotide induces rectal NE carcinoma to apoptosis and
      inhibits angiogenesis in the tumor. These result in tumor necrosis. Octreotide
      has an antitumor effect on rectal NE carcinoma.

PMID- 12239461
TI  - Cost analysis of breath test versus endoscopy for dyspepsia.
AB  - BACKGROUND: There is currently much debate on the best way to manage dyspepsia in
      the community and cost effectiveness is often discussed. We aim to perform a cost
      analysis of a test and treat strategy for Helicobacter pylori versus endoscopy
      using data based on the breath test service in Leicester. METHODS: Retrospective
      analysis of data acquired over the 1-year period from March 1, 1999, to February
      29, 2000, in a university teaching hospital. The main outcome measure was the
      cost of each management strategy. RESULTS: Referral to the breath test service
      cost pound 84.67 per person with dyspepsia (including treatment of positive
      patients and endoscopy cost of patients endoscoped). If the breath test service
      had not existed, referral for endoscopy would have cost pound 98.35 per person.
      This equates to a cost saving of pound 8,276 over the year studied for the 605
      patients referred. It also resulted in 353 fewer endoscopies being performed.
      CONCLUSION: Direct referral to a H. pylori breath test service saves money,
      avoids an unpleasant test for many people and reduces the endoscopy waiting list.

PMID- 12239462
TI  - Inhibition by female sex steroids of peristalsis in the guinea pig small
      intestine.
AB  - AIMS: The effects of steroid hormones on propulsive peristalsis in the intestine
      were investigated in order to compare their adverse effect profile on this
      clinically most important motor pattern. METHODS: Peristalsis in isolated
      segments of the guinea pig small intestine was triggered by luminal distension
      and recorded via the peristalsis-associated changes of the intraluminal pressure.
      Drug effects on muscular activity were investigated in a circular muscle
      preparation of the ileum. RESULTS: Estradiol and progesterone, but not
      testosterone, hydrocortisone or cholesterol (each at 3-30 microM), caused a
      prompt and concentration-related increase in the peristaltic pressure threshold
      at which propulsive muscle contractions were elicited. Mifepristone (RU-486; 30
      microM) did not prevent the inhibitory effect of progesterone, but blocked
      peristalsis per se. Pharmacological blockade of inhibitory neural pathways with
      N(G)-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), naloxone
      (opioid receptor antagonist), apamin or suramin plus pyridoxal phosphate-6
      azophenyl-2',4'-disulphonic acid (P2 purinoceptor blockers) counteracted the
      inhibitory effect of submaximally (10 microM), but not maximally (30 microM),
      effective concentrations of progesterone. Estradiol and progesterone depressed
      circular muscle contractions evoked by cholecystokinin octapeptide to a larger
      degree than responses to the tachykinin NK(1) receptor agonist GR-73,632.
      CONCLUSION: The peristaltic motor inhibition caused by sex steroids at micromolar
      concentrations arises primarily from a depressant action on intestinal muscle
      activity and may be particularly relevant for high-dose regimens of mifepristone.

PMID- 12239463
TI  - Active relaxation of human gallbladder muscle is mediated by ATP-sensitive
      potassium channels.
AB  - BACKGROUND: Active and significant relaxation of the human gallbladder must be
      one of the facets of its motility during both the filling and emptying cycle.
      Conflicting reports about the presence or significance of nitric oxide have been
      reported in the literature. The aim of this study was to investigate the role of
      nitric oxide and K(ATP) channels in human gallbladder muscle using isolated
      strips from human gallbladder. METHODS: Full thickness strips were obtained from
      56 human gallbladders and suspended under isometric tension in organ baths. The
      effect of nitric oxide donors and inhibitors on cholecystokinin octapeptide- and
      carbachol-induced contraction was examined. In separate experiments the effect of
      the K(ATP) channel activator, cromakalim, and the inhibitor, glibenclamide, were
      determined. RESULTS: Cromakalim induced a significant relaxation of agonist
      induced contraction in human gallbladder in vitro, an effect which was abolished
      by the K(ATP) channel inhibitor glibenclamide. No evidence of significant nitric
      oxide involvement in relaxation was observed. CONCLUSIONS: This study has
      demonstrated the presence of K(ATP) channels in human gallbladder for the first
      time. These are capable of causing significant relaxation in the presence of
      hormonal and muscarinic agonists and may represent a major pathway for
      gallbladder relaxation.

PMID- 12239464
TI  - Immunohistochemical analysis of ZO-1 in the duodenal mucosa of patients with
      untreated and treated celiac disease.
AB  - BACKGROUND/AIM: ZO-1 is a good marker for tight junction integrity which may be
      damaged in many intestinal diseases. ZO-1 can also accumulate in the cellular
      nucleus in addition to sites of cell-cell contact, suggesting a potential role in
      cellular proliferation and differentiation. We evaluated the expression and
      distribution of ZO-1 in patients with celiac disease before and after a gluten
      free diet. METHODS: The ZO-1 expression was evaluated semiquantitatively by means
      of immunohistochemical analysis in duodenal bioptic specimens of 10 consecutive
      patients with celiac disease before and after a gluten-free diet and in 10
      controls. Furthermore, the nuclear staining was analyzed quantitatively,
      evaluating 3,000 cells for each count, and it was expressed as a percentage of
      labeled nuclei over the total of analyzed cells. RESULTS: The intestinal mucosa
      of untreated celiac disease patients shows a globally lower ZO-1 labeling than
      that of controls. The expression of ZO-1 in the treated celiac mucosa did not
      differ significantly from normal intestinal mucosa of healthy subjects. At the
      crypt level of untreated celiac mucosa, a low intensity of nuclear labeling (1.75
      +/- 0.32%) was found, while in both treated celiac disease patients and in normal
      subjects we observed a statistically significant higher percentage of strongly
      labeled nuclei (53.72 +/- 6.30% and 56.79 +/- 5.45%, respectively; p = 0.0002).
      CONCLUSIONS: Our data show a global underexpression of ZO-1 in the duodenal
      mucosa of active celiac disease patients. Gluten withdrawal allows a
      normalization of the ZO-1 expression in treated celiac disease patients.
      Furthermore, the particular pattern of ZO-1 resembles the cellular distribution
      in undifferentiated cells and may be the result of immaturity of the enterocytes
      in untreated celiac sprue.

PMID- 12239465
TI  - Protein-losing cytomegalovirus gastritis in a patient with Stevens-Johnson
      syndrome.
AB  - We present a case of protein-losing cytomegalovirus gastritis in a previously
      immunocompetent 14-year-old Japanese girl that occurred during treatment of drug
      (zonisamide)-induced Stevens-Johnson syndrome with hepatic failure. Her hepatic
      failure and symptoms of Stevens-Johnson syndrome were successfully treated with
      intravenous prednisolone and infusion of fresh-frozen plasma or albumin, as the
      occasion demanded. However, during the course of treatment, she complained of
      severe epigastralgia together with hypoproteinemia, and cytomegalovirus gastritis
      was found by endoscopic and histological examinations. The possible mechanism by
      which cytomegalovirus gastritis occurred in the present case and effective
      diagnostic procedures are discussed.

PMID- 12239466
TI  - The rectum: a window to irritable bowel syndrome?
AB  - This report summarizes current concepts and information gathered to date about
      the rectum in the irritable bowel syndrome (IBS) that were presented at the 10th
      meeting of IBiS Club held in Leuven, Belgium. A working group of experts in the
      field of IBS discussed whether the rectum or the whole colon is the better site
      to test in IBS patients and provided suggestions for a number of areas where
      further advances are required.

PMID- 12239467
TI  - The spatial relationship of gamma-aminobutyric acid (GABA) neurons and
      gonadotropin-releasing hormone (GnRH) neurons in larval and adult sea lamprey,
      Petromyzon marinus.
AB  - In this study we examined the spatial relationship of GABA-containing and GnRH
      containing neurons by immunocytochemistry and in situ hybridization in larval and
      adult brains of sea lamprey, Petromyzon marinus. In immunocytochemical studies,
      GABA-containing neurons were detected early in lamprey development, by day 20
      post-fertilization. At this time point, one population of GABA-containing neurons
      was visualized in the hypothalamus and preoptic area, and another population was
      located in the olfactory bulb of the telencephalon. By day 30 after
      fertilization, after the GABA neurons were detected, GnRH-containing neurons were
      visualized in the preoptic area/rostral hypothalamus region, adjacent to the GABA
      containing neurons in the wall of the third ventricle. Similarly, in adult
      lamprey brains distinct populations of both GABA- and GnRH-containing neurons
      were located in the hypothalamus adjacent to the third ventricle. To further
      establish a proximate relationship between GABA and GnRH, the mRNA for glutamate
      decarboxylase (GAD), the enzyme catalyzing GABA synthesis from glutamate, and
      GnRH were examined by in situ hybridization in the brains of larval lamprey.
      These studies also showed that GnRH and GAD are produced in cell populations in
      and around the third ventricle of the hypothalamus. This close spatial
      relationship of GABA neurons and GnRH neurons provides a basis for a regulatory
      role of GABA on GnRH neurons in the sea lamprey.

PMID- 12239468
TI  - Effects of lesions of nucleus taeniae on appetitive and consummatory aspects of
      male sexual behavior in Japanese quail.
AB  - Neurochemical, hodological and functional criteria suggest that the nucleus
      taeniae and parts of the adjacent archistriatum represent the avian homologue of
      parts of the mammalian amygdaloid complex. It has been proposed in particular
      that the nucleus taeniae is the homologue of the mammalian medial amygdala. In
      male quail, relatively large lesions to the posterior/medial archistriatum
      selectively decrease the expression of appetitive sexual behavior in a manner
      reminiscent of similar manipulations involving the medial amygdala in mammals. We
      investigated the effects of discrete lesions restricted to nucleus taeniae and of
      lesions to an adjacent part of the archistriatum (pars intermedium ventralis,
      AIv) on the expression of appetitive (ASB) and consummatory (CSB) aspects of male
      sexual behavior. ASB was measured by a learned social proximity response (after
      copulation a male quail stands in front of a window providing visual access to a
      female) and by the frequency of rhythmic cloacal sphincter movements. CSB was
      assessed by the frequency of mount attempts (MA) and cloacal contact movements
      (CCM). Lesions confined to nucleus taeniae and to AIv did not influence the
      acquisition or the maintenance of the two responses indicative of ASB. In
      contrast, lesions of nucleus taeniae significantly increased the occurrence
      frequencies of MA and CCM when administered before the beginning of behavior
      testing and increased the frequency of MA only when performed on sexually
      experienced subjects. No effect of AIv lesions could be detected. The discrepancy
      between these results and previous experiments in quail might reflect procedural
      differences, but more probably differences in locations of the lesions that were
      restricted in the current study to the anterior part of taeniae. Those in the
      Thompson study were in the posterior part of this nucleus. These findings
      indicate that there is a larger degree of functional heterogeneity in the nucleus
      taeniae than previously thought. The effects of taeniae lesions suggest that this
      nucleus, similar to the medial amygdala in mammals, might be implicated in the
      control of sexual satiety.

PMID- 12239469
TI  - Efferent connections of the cerebellum of the goldfish, Carassius auratus.
AB  - Efferent fiber connections of the corpus and valvula cerebelli in the goldfish,
      Carassius auratus, were studied using an anterograde neural fiber tracing
      technique. Efferent targets of the corpus cerebelli are the posterior
      parvocellular preoptic nucleus, the ventromedial and ventrolateral thalamic
      nucleus, dorsal posterior thalamic nucleus, periventricular nucleus of posterior
      tuberculum, dorsal periventricular pretectal nucleus, inferior lobe, optic
      tectum, torus semicircularis, nucleus of the medial longitudinal fascicle,
      nucleus ruber, dorsal tegmental nucleus, nucleus lateralis valvulae, reticular
      formation, torus longitudinalis, and the medial and lateral lobe of the valvula
      cerebelli. Projections to the posterior parvocellular preoptic nucleus and the
      periventricular nucleus of posterior tuberculum are not reported in previous
      studies. Efferent targets of the medial lobe of the valvula cerebelli are similar
      to that of the corpus cerebelli except for lacking a projection to the inferior
      lobe and torus longitudinalis, but showing one to the corpus cerebelli. On the
      other hand, the lateral lobe of the valvula cerebelli projects only to the dorsal
      zone of the periventricular hypothalamus, the diffuse nucleus of the inferior
      lobe, corpus mamillare, vagal lobe and the corpus cerebelli. There are
      topographical projections from the lateral valvula to the inferior lobe. These
      results suggest that the function of the corpus and medial lobe of the valvula
      cerebelli include not only motor control but also functions similar to the
      mammalian higher cerebellum. This study also suggests that there are obvious
      functional divisions between the medial and lateral lobes of the valvula
      cerebelli.

PMID- 12239470
TI  - Intracellular recording and staining of neurons in the pigeon nucleus lentiformis
      mesencephali.
AB  - The pretectal nucleus lentiformis mesencephali in pigeons is involved in
      optokinetic nystagmus and consists of lateral (nLMl) and medial (nLMm) subnuclei.
      The present study using intracellular recordings and brain slices shows that
      pretectal cells respond to depolarizing current injection in different ways. Type
      I cells (32%) fire spontaneously and have regular spikes. Type II cells (20%)
      discharge regular spikes, whose frequency increases as current intensity
      increases. Type III cells (8%) produce a series of bursts, each of which consists
      of 2-5 spikes depending on current intensities. Type IV cells (39%) fire several
      spikes in a cluster at the onset of current injection and are then rapidly
      adapted. One cell of type V (1%) shows spontaneous firing and is inactivated by
      depolarizing currents. Cells of types III and V are only found in nLMm, and other
      types of cells exist in both subnuclei. This physiological difference might be a
      bias due to the small sampling of cells. Twenty-six cells are labeled with dye
      and they could be categorized into fusiform (23.1%), piriform (7.7%), or
      multipolar (69.2%) cells. Some correlation seems to exist between the
      physiological and morphological properties of pretectal neurons. Statistically,
      the somatic size of nLMm cells is significantly larger than that of nLMl cells,
      indicating that the nucleus could be divided cytoarchitecturally into
      magnocellular and parvocellular components as suggested previously.

PMID- 12239471
TI  - Alternative method for connecting a removable gingival extension and fixed
      partial denture: a clinical report.
AB  - In terms of esthetics and hygiene, defects in the alveolar ridge can complicate
      the design and fabrication of fixed partial dentures. When missing anterior teeth
      are restored, it may be difficult to achieve a satisfactory appearance without
      the correction of soft tissue and alveolar defects. When surgical intervention is
      not an option, a removable gingival extension and fixed prosthesis may be
      considered. This clinical report describes the use of a custom-made pin system
      (rather than intra- or extra-coronal attachments) to esthetically connect a
      removable gingival extension to a fixed partial denture.

PMID- 12239472
TI  - Relative translucency of six all-ceramic systems. Part I: core materials.
AB  - STATEMENT OF PROBLEM: All-ceramic restorations have been advocated for superior
      esthetics. Various materials have been used to improve ceramic core strength, but
      it is unclear whether they affect the opacity of all-ceramic systems. PURPOSE:
      This study compared the translucency of 6 all-ceramic system core materials at
      clinically appropriate thicknesses. MATERIALS AND METHODS: Disc specimens 13 mm
      in diameter and 0.49 +/- 0.01 mm in thickness were fabricated from the following
      materials (n = 5 per group): IPS Empress dentin, IPS Empress 2 dentin, In-Ceram
      Alumina core, In-Ceram Spinell core, In-Ceram Zirconia core, and Procera AllCeram
      core. Empress and Empress 2 dentin specimens also were fabricated and tested at a
      thickness of 0.77 +/- 0.02 mm (the manufacturer's recommended core thickness is
      0.8 mm). A high-noble metal-ceramic alloy (Porc. 52 SF) served as the control,
      and Vitadur Alpha opaque dentin was used as a standard. Sample reflectance (ratio
      of the intensity of reflected light to that of the incident light) was measured
      with an integrating sphere attached to a spectrophotometer across the visible
      spectrum (380 to 700 nm); 0-degree illumination and diffuse viewing geometry were
      used. Contrast ratios were calculated from the luminous reflectance (Y) of the
      specimens with a black (Yb) and a white (Yw) backing to give Yb/Yw with CIE
      illuminant D65 and a 2-degree observer function (0.0 = transparent, 1.0 =
      opaque). One-way analysis of variance and Tukey's multiple-comparison test were
      used to analyze the data (P<.05). RESULTS: Contrast ratios in order of most
      translucent to most opaque were as follows: Vitadur Alpha 0.60 +/- 0.03, Empress
      (0.5 mm) 0.64 +/- 0.01, In-Ceram Spinell 0.67 +/- 0.02, Empress 2 (0.5 mm) 0.68
      +/- 0.02, Empress (0.8 mm) 0.72 +/- 0.01, Procera 0.72 +/- 0.01, Empress 2 (0.8
      mm) 0.74 +/- 0.01, In-Ceram Alumina 0.87 +/- 0.01, In-Ceram Zirconia 1.00 +/-
      0.01, and 52 SF alloy 1.00 +/- 0.00. CONCLUSION: Within the limitations of this
      study, there was a range of ceramic core translucency at clinically relevant core
      thicknesses. In order of decreasing translucency, the ranges were Vitadur Alpha
      dentin (standard) > In-Ceram Spinell > Empress, Procera, Empress 2 > In-Ceram
      Alumina > In-Ceram Zirconia, 52 SF alloy.

PMID- 12239473
TI  - Relative translucency of six all-ceramic systems. Part II: core and veneer
      materials.
AB  - STATEMENT OF PROBLEM All-ceramic core materials with various strengthening
      compositions have a range of translucencies. It is unknown whether translucency
      differs when all-ceramic materials are fabricated similarly to the clinical
      restoration with a veneered core material. PURPOSE: This study compared the
      translucency of 6 all-ceramic materials veneered and glazed at clinically
      appropriate thicknesses. MATERIALS AND METHODS: Core specimens (n = 5 per group)
      of Empress dentin, Empress 2 dentin, In-Ceram Alumina, In-Ceram Spinell, In-Ceram
      Zirconia, and Procera AllCeram were fabricated as described in Part I of this
      study and veneered with their corresponding dentin porcelain to a final thickness
      of 1.47 +/- 0.01 mm. These specimens were compared with veneered Vitadur Alpha
      opaque dentin (as a standard), a clear glass disc (positive control), and a high
      noble metal-ceramic alloy (Porc. 52 SF) veneered with Vitadur Omega dentin
      (negative control). Specimen reflectance was measured with an integrating sphere
      attached to a spectrophotometer across the visible spectrum (380 to 700 nm); 0
      degree illumination and diffuse viewing geometry were used. Measurements were
      repeated after a glazing cycle. Contrast ratios were calculated from the luminous
      reflectance (Y) of the specimens with a black (Yb) and a white backing (Yw) to
      give Yb/Yw with CIE illuminant D65 and a 2-degree observer function (0.0 =
      transparent, 1.0 = opaque). One-way analysis of variance and Tukey's multiple
      comparison test were used to analyze the data (P<.05). RESULTS: Significant
      differences in contrast ratios were found among the ceramic systems tested when
      they were veneered (P<.0001) and after the glazing cycle (P<.0001). Significant
      changes in contrast ratios (P<.0001) also were identified when the veneered
      specimens were glazed. CONCLUSION: Within the limitations of this study, a range
      of translucency was identified in the veneered all-ceramic systems tested. Such
      variability may affect their ability to match natural teeth. The glazing cycle
      resulted in decreased opacity for all test materials except the completely opaque
      In-Ceram Zirconia and metal-ceramic specimens.

PMID- 12239474
TI  - Inner canthal distance and geometric progression as a predictor of maxillary
      central incisor width.
AB  - STATEMENT OF PROBLEM: Estimating the mesiodistal width of maxillary central
      incisors may be difficult when artificial teeth are selected for edentulous
      subjects. PURPOSE This study examined the relationship between inner canthal
      distance and maxillary central incisor mesiodistal width in terms of the
      geometric progression popularly known as the golden proportion. MATERIAL AND
      METHOD: Two hundred twenty-nine dentate Saudi subjects (120 males, 109 females;
      mean age 21.46 years) free from facial and dental deformities were examined. The
      mesiodistal width of each maxillary central incisor was measured between its
      interproximal contact points. The inner canthal distance was measured from medial
      angle to medial angle of the palpebral fissures of the eyes. The common ratios of
      geometric progression are 0.618 and 1.618. The inner canthal distance of each
      subject was multiplied by a decreasing function value of the geometric
      progression term (0.618) to provide the combined width of 2 central incisors. The
      product was then divided by 2 to obtain the width of a single maxillary central
      incisor. A t test was used to identify any significant differences in mesiodistal
      tooth width and inner canthal distance by gender. Agreement between the measured
      and calculated central incisor widths was evaluated with Pearson's correlation
      coefficients, as was intraexaminer reliability. Significance was set at
      alpha=.05. RESULTS: The mean inner canthal distance of male and female subjects
      was 28.7 +/- 1.7 mm and 27.9 +/- 2.1 mm, respectively. The mean maxillary central
      incisor width of male and female subjects was 8.87 +/- 0.5 mm and 8.68 mm +/- 0.4
      mm, respectively. Differences between the mean values for both measurements were
      significant (P =.002). The actual and calculated widths of the natural maxillary
      central incisors were found to be highly correlated (r =.943). CONCLUSION: Within
      the population tested, a significantly higher mean inner canthal distance and
      maxillary central incisor width were recorded for male subjects. Inner canthal
      distance, when multiplied by a decreasing function value of the geometric
      progression term and then divided by 2, was a reliable predictor of maxillary
      central incisor width.

PMID- 12239476
TI  - Delayed linear expansion of improved dental stone.
AB  - STATEMENT OF PROBLEMS: Specification 25 of the American Dental Association (ADA)
      states that final setting expansion measurements of improved dental stone are
      made 2 hours after mixing. In a limited pilot study on selected type IV and V
      dental stones, measurements showed delayed linear expansion or early contraction
      continuing up to 120 hours. PURPOSE: The objectives of this in vitro study were
      to measure the linear setting expansion of 6 ADA type IV and V dental stones, to
      compare their expansion at 2 hours relative to ADA Specification 25, and to
      characterize expansion changes up to 120 hours. MATERIAL AND METHODS: The
      improved dental stones tested in this study were Die-Keen, Jade Stone, Vel-Mix,
      ResinRock, Fuji Rock, and Silky Rock. Mixing was performed in accordance with a
      standardized technique and the manufacturers' instructions. The mixes were poured
      into an electronic expansion-measuring device, and setting expansion values were
      continuously measured and recorded for 120 hours. The collected data were
      subjected to a 2-way repeated-measures multivariate analysis of variance at
      alpha=.05. Planned comparisons between the 2-hour experimental and 2-hour
      manufacturer expansion values were made at the 95% confidence interval. RESULTS:
      All stones showed higher mean linear expansion values at 120 hours than at 2
      hours. Expansion was essentially complete at 96 hours for all stones except
      ResinRock. Die-Keen exhibited the highest total mean setting expansion (0.35% +/-
      0.013%), and Silky Rock exhibited the lowest mean linear expansion (0.14% +/-
      0.008%) at 120 hours. Multivariate analysis of variance revealed significant
      interactions between stone and time (P<.0001). Mean expansion values at 2 hours
      were comparable to those stated by the manufacturer except for Die-Keen and Jade
      Stone. CONCLUSION: Within the parameters of this study, all dental stones tested
      exhibited continued expansion while setting under clinical conditions. The amount
      of expansion varied significantly among the materials, with 22% to 71% of the
      expansion occurring after 2 hours. Die-Keen exhibited the highest total mean
      expansion but had the least amount of expansion after 2 hours; both Die-Keen and
      Silky Rock remained stable after 72 hours.

PMID- 12239475
TI  - Prospective clinical trial of dental implants in persons with ectodermal
      dysplasia.
AB  - STATEMENT OF PROBLEMS: Ectodermal dysplasia is a hereditary condition in which
      hypodontia is the second most frequently occurring sign. Hypodontia is associated
      with lack of development of the alveolar ridge and results in less volume of bone
      for support of conventional prostheses. Minimal development of the alveolar ridge
      can affect the bone volume available for the placement of dental implants.
      PURPOSE: This clinical trial evaluated the survival of implants placed in
      individuals with a form of ectodermal dysplasia and severe hypodontia. MATERIAL
      AND METHODS: Two hundred sixty-four titanium endosteal dental implants were
      placed in 51 subjects: 37 males and 14 females between the ages of 8 and 68 (mean
      age 20.5 years, median age 16.5 years). Two hundred forty-three implants were
      placed in the anterior mandible, and 21 were placed in the anterior maxilla with
      a 2-stage surgical protocol. Either fixed-detachable dentures or bar-clip
      overdentures were provided. Subjects were followed up for 0 to 78 months after
      second-stage surgery. Kaplan-Meier survival rates and curves were produced to
      describe the survival of the implants for the different age groups and implant
      locations. Repeated-measures Cox regression models were used to evaluate the
      hazard ratios for age and location, with alpha=.05 as the criteria for
      significance. RESULTS: Of the 243 implants placed in the anterior mandible, 221
      (91%) survived. Of the 21 implants placed in the anterior maxilla, 16 (76%)
      survived. Fourteen of the 51 (27%) subjects had a failed implant. All but 2
      failures occurred before or at second-stage surgery. Implant-supported prostheses
      were provided for all patients. CONCLUSION: Within the limitations of this study,
      the results support the continued use of endosteal dental implants in this
      patient population with appropriate precautions in the maxilla.

PMID- 12239477
TI  - Effect of finishing time and techniques on marginal sealing ability of two
      composite restorative materials.
AB  - STATEMENT OF PROBLEMS: Finishing of composites may adversely influence the
      sealing ability of direct adhesive restorations. PURPOSE: This study was
      conducted to determine whether finishing time and techniques under wet or dry
      conditions affect the microleakage of 2 types of class V composite restorations.
      MATERIAL AND METHODS: Eighty class V preparations were made in the buccal
      surfaces of noncarious molars with the occlusal margins ending in enamel and the
      gingival margins in dentin. Dental adhesive (Single Bond) was applied according
      to the manufacturer's instructions. Half of the preparations were restored with a
      microfilled composite (Silux Plus) and the other half with a hybrid composite
      (Filtek Z250). Within each major composite group (n = 40), 4 subgroups (n = 10)
      were established based on finishing technique (diamond finishing burs or aluminum
      oxide discs) and finishing time (immediate or delayed by 24 hours). The specimens
      were stored for 24 hours in 37 degrees C water, thermocycled for 250 cycles
      between 5 degrees C and 55 degrees C, immersed in 2% methylene blue solution for
      another 24 hours, and sectioned longitudinally. For both enamel and dentin
      margins, dye solution penetration at the tooth/composite interface was scored
      from 0 to 4 under stereoscopy at original magnification x 20. Data were analyzed
      with the Kruskal-Wallis test (P<.05). RESULTS: Significantly lower leakage scores
      were recorded for teeth restored with microfilled composite and finished under
      wet conditions after 24 hours (P<.01). No significant differences were found
      among the hybrid composite groups. CONCLUSION: For microfilled composite
      restorations on dentin margins, delayed wet finishing with diamond burs resulted
      in significantly lower microleakage scores than all other finishing protocols.
      Hybrid composite restorations had equivalent levels of microleakage regardless of
      the finishing method.

PMID- 12239478
TI  - Quality of removable partial dentures worn by the adult U.S. population.
AB  - STATEMENT OF PROBLEMS: Research-based assessments of the quality of removable
      partial dentures (RPDs), especially within a large patient population, are
      lacking. PURPOSE: This study evaluated the prevalence and quality of RPDs by use
      of the National Health and Nutrition Survey (NHANES III) data set. MATERIAL AND
      METHODS: Estimates of the health and nutritional status of the American
      population were obtained from the NHANES III data set (1988-1994). Calibrated
      dentists performed dental examinations on 17,884 adults. If the subject wore an
      RPD, its quality was assessed with 5 criteria: integrity, tooth wear, the
      presence of temporary reline material or adhesive, stability, and retention. In
      this study, the data on RPD defects were used to assess the prevalence of
      problems. The original population was divided into 4 subgroups: paired RPD data =
      subjects wearing both maxillary and mandibular RPDs (n = 600 prostheses, 300
      maxillary and 300 mandibular); single RPD data = subjects with only one RPD (n =
      1003 prostheses, 511 maxillary and 492 mandibular); maxillary versus mandibular
      RPD data = all subjects with all RPDs (n = 1603 prostheses, 811 maxillary and 792
      mandibular); and pooled RPD data = all subjects with a single RPD plus subjects
      with 2 RPDs, counting only the RPD with the most defects (n = 1303 prostheses,
      674 maxillary and 629 mandibular). The subjects were analyzed with descriptive
      statistics. The distribution of defects in the RPDs was examined for possible
      associations with chi(2) tests. The paired data for patients with both maxillary
      and mandibular RPDs were analyzed with Wilcoxon signed rank tests. The prevalence
      of RPDs as a function of patient age and the association between RPD defects and
      patient age were analyzed with chi(2) tests. The results were considered highly
      significant at P<.0001 and significant at P<.05. RESULTS: Of the 17,884 adults
      who underwent a dental examination, 1306 had RPDs. Three patients were excluded
      because their records were incomplete, leaving 1303 patients available for
      analysis. Most of the prostheses examined (65%) had at least 1 defect. Lack of
      stability was the most prevalent single defect. Distinctions in the type and
      prevalence of defects were observed between mandibular and maxillary RPDs.
      Mandibular RPDs had significantly more problems related to retention, whereas
      maxillary RPDs had significantly more problems related to the presence of reline
      material and to integrity defects. Tooth wear defects were significantly
      associated with patient age (P<.0001). Only one third of the RPDs were considered
      satisfactory according to NHANES III criteria. CONCLUSION: A review of the
      database used in this study indicated that, in spite of a decline in tooth loss,
      RPDs are still used in all age cohorts, including young adults. A large number of
      RPDs were found to have defects.

PMID- 12239479
TI  - The effect of multicolored machinable ceramics on the esthetics of all-ceramic
      crowns.
AB  - STATEMENT OF PROBLEMS: Computer-aided design/computer-assisted machining systems
      offer the possibility of fabricating restorations from one machinable ceramic
      block. Whether multishaded blocks improve esthetic results and are a viable
      alternative to individually stained ceramics has not been fully determined.
      PURPOSE: The aim of this investigation was to examine the effect of multishaded
      blocks on the esthetic appearance of all-ceramic CEREC crowns and compare these
      crowns with single-shade and stained restorations. MATERIAL AND METHODS: Ten
      subjects were included in this study. For each subject, 6 different crowns were
      milled with the use of a CEREC machine. One crown was milled from each of the
      following machinable ceramic materials: CEREC Vitablocs Mark II in classic
      colors; Vitablocs Mark II in 3D-Master colors; Vitablocs Mark II in either
      classic or 3D-Master colors, with additional staining; Megadenta Bloxx
      multishaded; Mark II experimental multilayer; and an experimental multilayer
      leucite ceramic. Three independent examiners assessed the esthetic appearance of
      crowns fabricated to match each subject's anterior tooth shade. A scale of 1 to 6
      was used to score the shade match and esthetic adaptation of each crown, with 1
      representing excellent characteristics and 3.5 serving as the threshold for
      clinical acceptability. The examiners' scores were averaged, and the mean values
      were analyzed with the Wilcoxon signed rank test (P<or=.05). RESULTS: Only
      individually stained Mark II restorations achieved a mean score below the
      threshold of 3.5 for all 10 subjects. These restorations were significantly more
      esthetic (P<or=.05) than restorations fabricated from all other materials except
      the Mark II experimental multilayer ceramic. The second best results were
      obtained for crowns made from single-shaded Mark II 3D-Master blocks: 6 out of 10
      restorations were scored below 3.5. Two of the layered materials (Mark II
      experimental and Bloxx) followed with 5 acceptable restorations out of 10.
      CONCLUSION: Within the limitations of this study, the results provide no evidence
      that multicolored machinable ceramics improve the esthetics of all-ceramic
      crowns.

PMID- 12239480
TI  - Clinical evaluation of two adhesive composite cements for the suppression of
      dentinal cold sensitivity.
AB  - STATEMENT OF PROBLEMS: Postoperative cold sensitivity after the cementation of
      indirect restorations with composite cements has been reported frequently but not
      scientifically documented. PURPOSE: This controlled clinical study was designed
      to simulate the dentin/composite cement interface immediately after cementation
      of a cast restoration. The desensitizing capabilities of a composite cement that
      contains a self-etching, dual-polymerizing resin adhesive system were compared
      with those of a composite cement that use phosphoric acid etching followed by a
      single-bottle, light-activated primer/resin-based adhesive. MATERIAL AND METHODS:
      The hypersensitive root surfaces of selected teeth were randomized to receive 1
      of 3 treatments: coating with a self-etching adhesive (Linkmax) and its
      respective cement, coating with a conventionally etched adhesive (RelyX ARC) and
      its cement, or no treatment (negative control). The sample size was 22. Dentin
      sensitivity was ascertained with an accurate cold testing device that slowly
      decreased in temperature. Tooth sensitivity was measured both immediately and at
      7 days after placement. Two-way analysis of variance and Fisher's least
      significant difference test (P<.05) were used to determine whether significant
      differences existed as a function of treatment type or time. RESULTS: Immediately
      after placement, the self-etching adhesive and its respective cement resulted in
      more suppression of cold sensitivity than no treatment (control); with Linkmax
      treatment, the temperature at which teeth responded was reduced by 8.4 degrees C.
      The conventionally etched adhesive and its cement reduced the temperature at
      which teeth responded by 9.4 degrees C. After 1 week, these temperature
      reductions were 7.0 degrees C and 4.3 degrees C, respectively. Untreated controls
      at the 2 intervals showed a mean decrease in sensitivity to cold of 3.6 degrees C
      and 4.1 degrees C. Statistical analysis showed type of composite cement to be a
      significant factor. CONCLUSION: Within the limitations of this study and in
      comparison to untreated control teeth, Linkmax treatment resulted in a
      significant reduction in tooth root sensitivity over 1 week (P=.02), whereas
      RelyX ARC did not (P=.066).

PMID- 12239481
TI  - Histologic and radiographic assessment of caries-like lesions localized at the
      crown margin.
AB  - STATEMENT OF PROBLEMS: Little is known about the impact of crown margins on the
      demineralization and remineralization process or on the interpretation of
      radiographs for the detection of early secondary caries. PURPOSE: The aim of this
      study was to correlate the findings from 2 different radiographic techniques with
      the results of a histologic assessment of carieslike lesions at the crown margin.
      MATERIAL AND METHODS: Ten fully impacted third molars were extracted and restored
      with complete metal crowns with chamfer preparations. For each tooth, the
      prepared margin ended in enamel on one side and extended into cementum/dentin on
      the other. After being thoroughly cleaned, the teeth were covered with wax except
      for a 2- x 3-mm window at the crown margin in each of 2 test areas localized at
      the interproximal enamel and cementum/dentin junction. During demineralization
      with 6% hydroxyethyl cellulose gel at pH 4.9, direct digital radiographs or
      conventional radiographs were made at baseline and after 7, 14, 21, and 28 days.
      Each radiograph was blinded and examined for the presence/absence of lesions by 3
      calibrated observers who used predetermined criteria required for receiver
      operating characteristic (ROC) analysis. After 28 days, the teeth were imbibed
      with methyl methacrylate and serially ground sectioned for assessment of the
      lesions in polarized light. Morphometric analysis of lesion extension included
      the calculation of mean values and standard deviations. Kappa and ROC analysis
      were applied to assess radiographs made at different demineralization time
      periods, localization of the crown margins in enamel or cementum/dentin, and
      direct digital and conventional radiographs. Data were tested for normal
      distribution (QQ plot), and statistical differences were calculated with Tukey's
      honestly significant difference post hoc test. RESULTS: Radiographic evaluation
      revealed only slight interexaminer agreement (Kappa) for enamel lesions (direct
      digital 0.19, conventional radiographs 0.2) and a fair interexaminer agreement
      for cementum/dentin lesions (direct digital 0.35, conventional radiographs 0.33).
      ROC analysis revealed no differences between the radiographic techniques. Lesions
      localized in cementum/dentin (direct digital 0.86 +/- 0.14, conventional
      radiographs 0.86 +/- 0.09) were diagnosed more reliably than those in enamel
      (direct digital 0.79 +/- 0.05, conventional radiographs 0.72 +/- 0.10). As
      microscopically assessed, the depth of lesions in enamel was less than that of
      lesions in cementum/dentin (49.3 +/- 7.3 microm vs 89.5 +/- 13.2 microm).
      Erosions were found in cementum/dentin (depth 25.2 +/- 5.3 microm). CONCLUSION:
      Within the limitations of this study, small artificial lesions were detected
      equally well by conventional and direct digital radiography. However, because of
      low interexaminer agreement, the radiographic assessment did not reproduce true
      histopathologic lesion characteristics documented by morphometry of serial ground
      sections.

PMID- 12239482
TI  - Annual review of selected dental literature: report of the Committee on
      Scientific Investigation of the American Academy of Restorative Dentistry.

PMID- 12239483
TI  - Twenty years of progress in implant prosthodontics.
AB  - Prosthodontic focus on the restoration of osseointegrated dental implants has
      evolved dramatically in the last 20 years. Many of the original guiding
      principles for restoring implants have changed and/or disappeared altogether, and
      new ideas have taken their place. It is appropriate that this evolution be
      examined with a 2-fold focus. First, the art and science of prosthodontics as it
      relates to dental implants today is the result of very real and important lessons
      learned during the past 2 decades. Second, an appreciation of the history of
      implant prosthodontics as it relates to osseointegration gives insight into the
      future direction of research and clinical exploration aimed at continually
      improving the state of the art and, ultimately, the quality of care provided to
      patients. This article reviews what the authors consider the most important
      aspects of the evolution of osseointegrated implants. Pertinent literature was
      selected for citation, but the discussion does not represent a comprehensive
      review of the literature.

PMID- 12239484
TI  - Transforming an existing fixed provisional prosthesis into an implant-supported
      fixed provisional prosthesis with the use of healing abutments.
AB  - Maintaining a fixed provisional prosthesis through all phases of complex implant
      prosthodontic therapy for a soon-to-be completely edentulous arch is a difficult
      task. This article focuses on the treatment phase in which teeth and/or
      transitional implants supporting a provisional fixed partial denture are removed.
      The described technique makes use of healing abutments to support a modified
      provisional fixed partial denture. This protocol ensures patient comfort and
      allows proper soft tissue healing before definitive implant abutment selection.
      It also eliminates the placement of interim implant abutments.

PMID- 12239485
TI  - Custom precision attachment housings for removable partial dentures.
AB  - Limited space for extracoronal attachments is a serious complication in the
      design and fabrication of a precision attachment removable partial denture. A
      custom metal-ceramic housing joined to the partial framework with laser welding
      offers strength and improved esthetics while requiring minimal space. This
      article presents the technical aspects of custom housing construction.

PMID- 12239486
TI  - Impression technique for partially edentulous patients.
AB  - This article describes an implant impression technique for partially edentulous
      patients in which impression plaster and irreversible hydrocolloid are used. The
      technique ensures accuracy, ease of manipulation, and decreased working time.

PMID- 12239487
TI  - Fabricating custom provisional restorations for the ITI solid abutment system.
AB  - This article describes a technique for the quick and accurate fabrication of
      custom acrylic resin provisional restorations for the ITI implant system.
      Materials and procedures common to fixed prosthodontics are used. The technique
      should necessitate no more chairtime than the fabrication of custom acrylic
      provisional restorations for conventional fixed prostheses.

PMID- 12239488
TI  - Proper loading of impression tray minimizes inaccuracies.

PMID- 12239490
TI  - Simplified technique for blocking out undercuts during direct overdenture matrix
      attachment.

PMID- 12239489
TI  - Stippling complete dentures with a nonconcentric bur.

PMID- 12239491
TI  - A simple technique to facilitate investment flow through screw access channels.

PMID- 12239492
TI  - Lack of an association between medicare supplemental insurance and delay in
      seeking emergency care for patients with myocardial infarction.
AB  - STUDY OBJECTIVE: Previous studies have shown that Medicare patients without
      supplemental insurance are less likely to receive preventive services, such as
      mammography. The effect of supplemental insurance on the appropriate use of
      emergency services is unknown. We sought to determine whether the absence of
      supplemental Medicare coverage is associated with increased delay in seeking care
      for acute myocardial infarction. METHODS: In this retrospective cohort study, we
      compared the time from symptom onset to hospital arrival (the time-delay
      interval) in Medicare patients with and without supplemental insurance coverage
      who presented with an acute myocardial infarction to 1 of 19 hospitals in King
      County, WA, from 1989 to 1993. There were 1,373 patients with Medicare-only
      coverage and 2,050 patients with Medicare plus supplemental insurance coverage.
      RESULTS: The age-, sex-, and race-adjusted median time delay was 135 minutes for
      the Medicare-only group and 130 minutes for the Medicare plus supplemental
      insurance group (P =.34; 95% confidence interval for median time-delay difference
      in minutes -5 to 10). There was no significant association between the presence
      of Medicare supplemental insurance coverage and time delay in Cox regression
      models, which also adjusted for event year, income, education, past cardiac
      history, and clinical symptoms. CONCLUSION: For this cohort of Medicare patients,
      the absence of supplemental insurance coverage did not lead to significantly
      increased delays in seeking care for myocardial infarction. Lack of supplemental
      insurance for Medicare patients might not have as great an effect on the use of
      emergency services as it has on other health care services.

PMID- 12239493
TI  - Emergency department crowding as a health policy issue: past development, future
      directions.

PMID- 12239494
TI  - How well do clinical practice guidelines guide clinical practice?

PMID- 12239495
TI  - Rapid antigen assay for the diagnosis of pneumococcal bacteremia in children: a
      preliminary study.
AB  - STUDY OBJECTIVE: We determine the sensitivity of a new Streptococcus pneumoniae
      antigen assay in children with S pneumoniae bacteremia and also determine the
      specificity of the assay in afebrile children without apparent pneumococcal
      infection. METHODS: We enrolled 2 groups of children, 3 months to 5 years of age,
      presenting to an urban pediatric emergency department or hospital-based clinic
      between January 1, 2000, and January 1, 2001. The study group included patients
      with S pneumoniae bacteremia. The control group included patients without fever
      or identified focal bacterial infection (other than a urinary tract infection).
      We excluded from the control group patients with a recent diagnosis (prior 4
      weeks) of bacteremia, pneumonia, meningitis, acute otitis media, or other
      suspected S pneumoniae infection. RESULTS: Ninety-six patients were enrolled: 24
      children with S pneumoniae bacteremia and 72 afebrile control patients. The assay
      produced a positive result in 23 of 24 patients with pneumococcal bacteremia,
      yielding a sensitivity of 95.8% (95% confidence interval [CI] 78.9% to 99.9%).
      The test result was negative in 67 of 72 afebrile patients without apparent
      pneumococcal infection, yielding a specificity in this population of 93.0% (95%
      CI 83.4% to 97.5%). CONCLUSION: This S pneumoniae assay demonstrated high
      sensitivity for the defined bacteremic population, as well as high specificity
      among afebrile children without apparent pneumococcal infection. Further study in
      febrile children at risk of pneumococcal bacteremia is needed before the value of
      the test in children at risk for invasive pneumococcal disease can be determined.

PMID- 12239496
TI  - Potential use of autoinjector-packaged antidotes for treatment of pediatric nerve
      agent toxicity.
AB  - STUDY OBJECTIVE: We sought to determine the feasibility of discharging Mark 1
      atropine and pralidoxime autoinjectors into small, sterile vials to facilitate
      the potential intramuscular injection of these antidotes, particularly
      pralidoxime, on a milligram per kilogram basis to small children. METHODS:
      Autoinjectors were swabbed with isopropyl alcohol and then discharged into
      emptied, sterile, plastic 10-mL vials. This was repeated with the investigator
      garbed in standard personal protective gloves and full face mask and hood. The
      autoinjector injection surfaces were cultured. RESULTS: The autoinjectors were
      easily discharged into the vials without need for practice or special dexterity,
      even when investigators were garbed in protective gear. A small core of rubber
      stopper might be injected into the vial, and thus, the vial contents need to be
      withdrawn through a filter needle before reinjection. The autoinjector injection
      surfaces were sterile after alcohol swabbing. CONCLUSION: Autoinjectors might be
      a readily available source of concentrated pralidoxime for potential
      intramuscular use in small children.

PMID- 12239497
TI  - Death of a child in the emergency department, a joint statement by the American
      Academy of Pediatrics and the American College of Emergency Physicians.

PMID- 12239498
TI  - The prevalence of latex-specific IgE in patients presenting to an urban emergency
      department.
AB  - STUDY OBJECTIVE: Since the first report of immediate hypersensitivity to latex
      was documented in 1979, latex allergy has been increasingly recognized as a
      medical problem in patient populations. However, there are no data available
      regarding the seroprevalence of latex sensitization in patients presenting to the
      emergency department. The overall aim of this study was to determine the
      prevalence of latex IgE seropositivity (L-IgE) in ED patients. METHODS: We
      measured latex-specific IgE antibodies among a convenience sample of 1,027
      patients using the AlaSTAT assay. We also measured serum IgE antibodies specific
      for 12 common inhalant allergens using the AlaTOP Microplate Allergy Screen
      assay. Demographic data were collected. Two questions related to latex allergy
      were queried. Descriptive statistics are presented. Point estimates and 95%
      confidence intervals (CIs) were calculated for each seroprevalence test. Odds
      ratios (ORs) and 95% CIs were used to assess the relationship between sex, race,
      and seropositivity to inhalant allergens and L-IgE. RESULTS: The participation
      rate was 90% (1,027). The mean age of the patients was 46.9 years, 47.6% (489)
      were male, and 13.9% (143) were white. Eighty-four (8.2%; 95% CI 6.5% to 10.0%)
      had positive L-IgE results, and 23.8% (20) of patients with positive L-IgE
      results were classified as having strongly positive results. Bivariate analyses
      showed that being nonwhite (OR 4.7; 95% CI 1.5 to 15.1) and being seropositive
      for inhalant allergens (OR 7.4; 95% CI 4.2 to 13.1) were associated with L-IgE.
      CONCLUSION: The prevalence of latex sensitization in our sampling is substantial
      and higher than previously estimated in the general adult population. The
      clinical significance of seropositivity requires further evaluation.

PMID- 12239499
TI  - Cardiogenic shock complicating acute carbon monoxide poisoning despite neurologic
      and metabolic recovery.
AB  - We report the cases of 2 previously healthy young patients with acute carbon
      monoxide intoxication who deteriorated to cardiogenic shock in the face of
      apparent metabolic and neurologic recovery. Prolonged exposure to sublethal
      levels of carbon monoxide (>24 hours, carboxyhemoglobin level of 20.4% and 22.6%)
      and massive binding of the toxin to myocardial myoglobin and mitochondrial
      cytochrome chain enzymes might explain their protracted cardiac failure. The good
      response to inotropic agents and the findings of repeated echocardiographic
      studies support the probable diagnosis of myocardial stunning. Complete cardiac
      recovery was observed in both patients.

PMID- 12239500
TI  - Massive OxyContin ingestion refractory to naloxone therapy.
AB  - OxyContin (oxycodone hydrochloride controlled release) is a long-acting
      preparation of oxycodone that is used as an opioid analgesic to treat chronic
      pain conditions. We report a patient who ingested a massive quantity of OxyContin
      and had altered mental status, noncardiogenic pulmonary edema, and
      hypoventilation that proved refractory to naloxone administration. She required
      mechanical ventilation for 3 days before recovering completely. The severity and
      length of poisoning was likely related both to the quantity and formulation of
      the oxycodone ingested.

PMID- 12239501
TI  - Economic impact of motor vehicle crashes.

PMID- 12239502
TI  - Understanding and using the new estimates on the economic impact of motor vehicle
      crashes.

PMID- 12239503
TI  - Birth by candlelight.

PMID- 12239504
TI  - Heal the healer.

PMID- 12239505
TI  - Emergency physicians and the victim of sexual assault.

PMID- 12239506
TI  - Academic department expansion: yesterday's news.

PMID- 12239508
TI  - Supreme Court renders final ADA decisions for this term.

PMID- 12239509
TI  - I'm changing the best I can!

PMID- 12239510
TI  - Bridges to CAM integration.

PMID- 12239512
TI  - Health care outcomes and the case manager.

PMID- 12239511
TI  - Taking action against moral distress.

PMID- 12239514
TI  - The Commission for Case Manager Certification widens eligibility criteria.

PMID- 12239515
TI  - Reimbursement for outpatient therapy with enoxaparin.

PMID- 12239516
TI  - Faculty case management: an innovative approach in a primary health care clinic.

PMID- 12239517
TI  - Serving the case management profession with excellence: Jean O'Leary. Interview
      by Sandra Lowery.

PMID- 12239519
TI  - Calling for entrepreneurs London.

PMID- 12239520
TI  - Improving proto-scientists' summers.

PMID- 12239522
TI  - Next-generation space telescope sets course for 2010 launch.

PMID- 12239521
TI  - More drugs, less protection.

PMID- 12239524
TI  - Japan celebrates safe launch after string of problems.

PMID- 12239523
TI  - US return may boost 'S' in UNESCO.

PMID- 12239527
TI  - Kosovo's ethnic divide blights UN science rebuilding plans.

PMID- 12239528
TI  - India shuts door on embryonic export market.

PMID- 12239529
TI  - Telescope to track speedy satellites.

PMID- 12239530
TI  - Pyramid find reopens lost chapter of history.

PMID- 12239533
TI  - Nosy neighbours.

PMID- 12239534
TI  - Bridging the culture gap.

PMID- 12239535
TI  - The many dangers of relying on a DNA database.

PMID- 12239536
TI  - Planted 'evidence' weakens case for DNA.

PMID- 12239537
TI  - Free consanguinity testing for all.

PMID- 12239538
TI  - Could we trust every future government?

PMID- 12239539
TI  - Europe is not yet ready for a research council.

PMID- 12239540
TI  - Element of confusion.

PMID- 12239541
TI  - Why response-mode research loses out.

PMID- 12239542
TI  - A fresh start for European science.

PMID- 12239548
TI  - Parkfield's unfulfilled promise.

PMID- 12239547
TI  - Animal reflections.

PMID- 12239549
TI  - Neurobiology: plasticity and the older owl.

PMID- 12239550
TI  - Light from darkness.

PMID- 12239551
TI  - Developmental biology: sharp peaks from shallow sources.

PMID- 12239552
TI  - Cell biology: proteins tracked in a flash.

PMID- 12239553
TI  - Physiology: unhealthy surprises.

PMID- 12239554
TI  - Conservation biology: science, sex and the kakapo.

PMID- 12239556
TI  - A delayed reaction.

PMID- 12239557
TI  - Gene regulation: reviving the message.

PMID- 12239558
TI  - Stimulating illusory own-body perceptions.
AB  - 'Out-of-body' experiences (OBEs) are curious, usually brief sensations in which a
      person's consciousness seems to become detached from the body and take up a
      remote viewing position. Here we describe the repeated induction of this
      experience by focal electrical stimulation of the brain's right angular gyrus in
      a patient who was undergoing evaluation for epilepsy treatment. Stimulation at
      this site also elicited illusory transformations of the patient's arm and legs
      (complex somatosensory responses) and whole-body displacements (vestibular
      responses), indicating that out-of-body experiences may reflect a failure by the
      brain to integrate complex somatosensory and vestibular information.

PMID- 12239559
TI  - Eukaryotic evolution: early origin of canonical introns.
AB  - Spliceosomal introns, one of the hallmarks of eukaryotic genomes, were thought to
      have originated late in evolution and were assumed not to exist in eukaryotes
      that diverged early -- until the discovery of a single intron with an aberrant
      splice boundary in the primitive 'protozoan' Giardia. Here we describe introns
      from a close relative of Giardia, Carpediemonas membranifera, that have boundary
      sequences of the normal eukaryotic type, indicating that canonical introns are
      likely to have arisen very early in eukaryotic evolution.

PMID- 12239560
TI  - Structure of the Sec23/24-Sar1 pre-budding complex of the COPII vesicle coat.
AB  - COPII-coated vesicles form on the endoplasmic reticulum by the stepwise
      recruitment of three cytosolic components: Sar1-GTP to initiate coat formation,
      Sec23/24 heterodimer to select SNARE and cargo molecules, and Sec13/31 to induce
      coat polymerization and membrane deformation. Crystallographic analysis of the
      Saccharomyces cerevisiae Sec23/24-Sar1 complex reveals a bow-tie-shaped
      structure, 15 nm long, with a membrane-proximal surface that is concave and
      positively charged to conform to the size and acidic-phospholipid composition of
      the COPII vesicle. Sec23 and Sar1 form a continuous surface stabilized by a non
      hydrolysable GTP analogue, and Sar1 has rearranged from the GDP conformation to
      expose amino-terminal residues that will probably embed in the bilayer. The
      GTPase-activating protein (GAP) activity of Sec23 involves an arginine side chain
      inserted into the Sar1 active site. These observations establish the structural
      basis for GTP-dependent recruitment of a vesicular coat complex, and for
      uncoating through coat-controlled GTP hydrolysis.

PMID- 12239561
TI  - Allowed and forbidden transitions in artificial hydrogen and helium atoms.
AB  - The strength of radiative transitions in atoms is governed by selection rules
      that depend on the occupation of atomic orbitals with electrons. Experiments have
      shown similar electron occupation of the quantized energy levels in semiconductor
      quantum dots--often described as artificial atoms. But unlike real atoms, the
      confinement potential of quantum dots is anisotropic, and the electrons can
      easily couple with phonons of the material. Here we report electrical pump-and
      probe experiments that probe the allowed and 'forbidden' transitions between
      energy levels under phonon emission in quantum dots with one or two electrons
      (artificial hydrogen and helium atoms). The forbidden transitions are in fact
      allowed by higher-order processes where electrons flip their spin. We find that
      the relaxation time is about 200 micro s for forbidden transitions, 4 to 5 orders
      of magnitude longer than for allowed transitions. This indicates that the spin
      degree of freedom is well separated from the orbital degree of freedom, and that
      the total spin in the quantum dots is an excellent quantum number. This is an
      encouraging result for potential applications of quantum dots as basic entities
      for spin-based quantum information storage.

PMID- 12239562
TI  - Forward scattering due to slow-down of the intermediate in the H + HD --> D +
      H(2) reaction.
AB  - Quantum dynamical processes near the energy barrier that separates reactants from
      products influence the detailed mechanism by which elementary chemical reactions
      occur. In fact, these processes can change the product scattering behaviour from
      that expected from simple collision considerations, as seen in the two classical
      reactions F + H(2) --> HF + H and H + H(2) --> H(2) + H and their isotopic
      variants. In the case of the F + HD reaction, the role of a quantized trapped
      Feshbach resonance state had been directly determined, confirming previous
      conclusions that Feshbach resonances cause state-specific forward scattering of
      product molecules. Forward scattering has also been observed in the H + D(2) -->
      HD + D reaction and attributed to a time-delayed mechanism. But despite extensive
      experimental and theoretical investigations, the details of the mechanism remain
      unclear. Here we present crossed-beam scattering experiments and quantum
      calculations on the H + HD --> H(2) + D reaction. We find that the motion of the
      system along the reaction coordinate slows down as it approaches the top of the
      reaction barrier, thereby allowing vibrations perpendicular to the reaction
      coordinate and forward scattering. The reaction thus proceeds, as previously
      suggested, through a well-defined 'quantized bottleneck state' different from the
      trapped Feshbach resonance states observed before.

PMID- 12239564
TI  - Testing time-predictable earthquake recurrence by direct measurement of strain
      accumulation and release.
AB  - Probabilistic estimates of earthquake hazard use various models for the temporal
      distribution of earthquakes, including the 'time-predictable' recurrence model
      formulated by Shimazaki and Nakata (which incorporates the concept of elastic
      rebound described as early as 1910 by H. F. Reid). This model states that an
      earthquake occurs when the fault recovers the stress relieved in the most recent
      earthquake. Unlike time-independent models (for example, Poisson probability),
      the time-predictable model is thought to encompass some of the physics behind the
      earthquake cycle, in that earthquake probability increases with time. The time
      predictable model is therefore often preferred when adequate data are available,
      and it is incorporated in hazard predictions for many earthquake-prone regions,
      including northern California, southern California, New Zealand and Japan. Here
      we show that the model fails in what should be an ideal locale for its
      application -- Parkfield, California. We estimate rigorous bounds on the
      predicted recurrence time of the magnitude approximately 6 1966 Parkfield
      earthquake through inversion of geodetic measurements and we show that, according
      to the time-predictable model, another earthquake should have occurred by 1987.
      The model's poor performance in a relatively simple tectonic setting does not
      bode well for its successful application to the many areas of the world
      characterized by complex fault interactions.

PMID- 12239563
TI  - An all-organic composite actuator material with a high dielectric constant.
AB  - Electroactive polymers (EAPs) can behave as actuators, changing their shape in
      response to electrical stimulation. EAPs that are controlled by external electric
      fields--referred to here as field-type EAPs--include ferroelectric polymers,
      electrostrictive polymers, dielectric elastomers and liquid crystal polymers.
      Field-type EAPs can exhibit fast response speeds, low hysteresis and strain
      levels far above those of traditional piezoelectric materials, with elastic
      energy densities even higher than those of piezoceramics. However, these polymers
      also require a high field (>70 V micro m(-1)) to generate such high elastic
      energy densities (>0.1 J cm(-3); refs 4, 5, 9, 10). Here we report a new class of
      all-organic field-type EAP composites, which can exhibit high elastic energy
      densities induced by an electric field of only 13 V micro m(-1). The composites
      are fabricated from an organic filler material possessing very high dielectric
      constant dispersed in an electrostrictive polymer matrix. The composites can
      exhibit high net dielectric constants while retaining the flexibility of the
      matrix. These all-organic actuators could find applications as artificial
      muscles, 'smart skins' for drag reduction, and in microfluidic systems for drug
      delivery.

PMID- 12239565
TI  - An unusual oviraptorosaurian dinosaur from China.
AB  - Oviraptorosaurians are an unusual group of theropod dinosaurs, with highly
      specialized skulls. Here we report a new oviraptorosaurian, Incisivosaurus
      gauthieri, gen. et sp. nov., from the lowest part of the Lower Cretaceous Yixian
      Formation of China. This oviraptorosaurian displays a number of characters closer
      to more typical theropods, such as a low skull and toothed jaws, thus greatly
      reducing the morphological gap between oviraptorosaurs and other theropods.
      Incisivosaurus has a pair of premaxillary teeth resembling rodent incisors and
      small, lanceolate cheek teeth with large wear facets. These dental features were
      previously unknown among theropods and suggest a herbivorous diet. The new
      discovery provides a case of convergent evolution and demonstrates that non-avian
      theropods were much more diverse ecologically than previously suspected.

PMID- 12239566
TI  - Incremental training increases the plasticity of the auditory space map in adult
      barn owls.
AB  - The plasticity in the central nervous system that underlies learning is generally
      more restricted in adults than in young animals. In one well-studied example, the
      auditory localization pathway has been shown to be far more limited in its
      capacity to adjust to abnormal experience in adult than in juvenile barn owls.
      Plasticity in this pathway has been induced by exposing owls to prismatic
      spectacles that cause a large, horizontal shift of the visual field. With prisms,
      juveniles learn new associations between auditory cues, such as interaural time
      difference (ITD), and locations in visual space, and acquire new
      neurophysiological maps of ITD in the optic tectum, whereas adults do neither.
      Here we show that when the prismatic shift is experienced in small increments,
      maps of ITD in adults do change adaptively. Once established through incremental
      training, new ITD maps can be reacquired with a single large prismatic shift. Our
      results show that there is a substantially greater capacity for plasticity in
      adults than was previously recognized and highlight a principled strategy for
      tapping this capacity that could be applied in other areas of the adult central
      nervous system.

PMID- 12239567
TI  - Odorant receptors instruct functional circuitry in the mouse olfactory bulb.
AB  - The mammalian olfactory system detects and discriminates thousands of odorants
      using many different receptors expressed by sensory neurons in the nasal
      epithelium. Axonal projections from these neurons to the main olfactory bulbs
      form reproducible patterns of glomeruli in two widely separated regions of each
      bulb, creating two mirror-symmetric maps of odorant receptor projections. To
      investigate whether odorant receptors organize neural circuitry in the olfactory
      bulb, we have examined a genetically modified mouse line, rI7 --> M71, in which a
      functionally characterized receptor, rI7, has been substituted into the M71
      receptor locus. Here we show that despite their ectopic location the resulting
      glomeruli are responsive to known ligands of the rI7 receptor, attract
      postsynaptic innervation by mitral/tufted cell dendrites, and endow these cells
      with responses that are characteristic of the rI7 receptor. External tufted cells
      receiving input from rI7 --> M71 glomeruli form precise intrabulbar projections
      that link medial and lateral rI7 --> M71 glomeruli anatomically, thus providing a
      substrate for coordinating isofunctional glomeruli. We conclude that odorant
      receptor identity in epithelial neurons determines not only glomerular
      convergence and function, but also functional circuitry in the olfactory bulb.

PMID- 12239568
TI  - Prestin is required for electromotility of the outer hair cell and for the
      cochlear amplifier.
AB  - Hearing sensitivity in mammals is enhanced by more than 40 dB (that is, 100-fold)
      by mechanical amplification thought to be generated by one class of cochlear
      sensory cells, the outer hair cells. In addition to the mechano-electrical
      transduction required for auditory sensation, mammalian outer hair cells also
      perform electromechanical transduction, whereby transmembrane voltage drives
      cellular length changes at audio frequencies in vitro. This electromotility is
      thought to arise through voltage-gated conformational changes in a membrane
      protein, and prestin has been proposed as this molecular motor. Here we show that
      targeted deletion of prestin in mice results in loss of outer hair cell
      electromotility in vitro and a 40-60 dB loss of cochlear sensitivity in vivo,
      without disruption of mechano-electrical transduction in outer hair cells. In
      heterozygotes, electromotility is halved and there is a twofold (about 6 dB)
      increase in cochlear thresholds. These results suggest that prestin is indeed the
      motor protein, that there is a simple and direct coupling between electromotility
      and cochlear amplification, and that there is no need to invoke additional active
      processes to explain cochlear sensitivity in the mammalian ear.

PMID- 12239569
TI  - Robustness of the BMP morphogen gradient in Drosophila embryonic patterning.
AB  - Developmental patterning relies on morphogen gradients, which generally involve
      feedback loops to buffer against perturbations caused by fluctuations in gene
      dosage and expression. Although many gene components involved in such feedback
      loops have been identified, how they work together to generate a robust pattern
      remains unclear. Here we study the network of extracellular proteins that
      patterns the dorsal region of the Drosophila embryo by establishing a graded
      activation of the bone morphogenic protein (BMP) pathway. We find that the BMP
      activation gradient itself is robust to changes in gene dosage. Computational
      search for networks that support robustness shows that transport of the BMP class
      ligands (Scw and Dpp) into the dorsal midline by the BMP inhibitor Sog is the key
      event in this patterning process. The mechanism underlying robustness relies on
      the ability to store an excess of signalling molecules in a restricted spatial
      domain where Sog is largely absent. It requires extensive diffusion of the BMP
      Sog complexes, coupled with restricted diffusion of the free ligands. We show
      experimentally that Dpp is widely diffusible in the presence of Sog but tightly
      localized in its absence, thus validating a central prediction of our theoretical
      study.

PMID- 12239570
TI  - Molecular basis of seasonal time measurement in Arabidopsis.
AB  - Several organisms have evolved the ability to measure daylength, or photoperiod,
      allowing them to adjust their development in anticipation of annual seasonal
      changes. Daylength measurement requires the integration of temporal information,
      provided by the circadian system, with light/dark discrimination, initiated by
      specific photoreceptors. Here we demonstrate that in Arabidopsis this integration
      takes place at the level of CONSTANS (CO) function. CO is a transcriptional
      activator that accelerates flowering time in long days, at least in part by
      inducing the expression of FLOWERING LOCUS T (FT). First, we show that precise
      clock control of the timing of CO expression, such that it is high during daytime
      only in long days, is critical for daylength discrimination. We then provide
      evidence that CO activation of FT expression requires the presence of light
      perceived through cryptochrome 2 (cry2) or phytochrome A (phyA). We conclude that
      an external coincidence mechanism, based on the endogenous circadian control of
      CO messenger RNA levels, and the modulation of CO function by light, constitutes
      the molecular basis for the regulation of flowering time by daylength in
      Arabidopsis.

PMID- 12239571
TI  - A regulatory cytoplasmic poly(A) polymerase in Caenorhabditis elegans.
AB  - Messenger RNA regulation is a critical mode of controlling gene expression.
      Regulation of mRNA stability and translation is linked to controls of poly(A)
      tail length. Poly(A) lengthening can stabilize and translationally activate
      mRNAs, whereas poly(A) removal can trigger degradation and translational
      repression. Germline granules (for example, polar granules in flies, P granules
      in worms) are ribonucleoprotein particles implicated in translational control.
      Here we report that the Caenorhabditis elegans gene gld-2, a regulator of
      mitosis/meiosis decision and other germline events, encodes the catalytic moiety
      of a cytoplasmic poly(A) polymerase (PAP) that is associated with P granules in
      early embryos. Importantly, the GLD-2 protein sequence has diverged substantially
      from that of conventional eukaryotic PAPs, and lacks a recognizable RRM (RNA
      recognition motif)-like domain. GLD-2 has little PAP activity on its own, but is
      stimulated in vitro by GLD-3. GLD-3 is also a developmental regulator, and
      belongs to the Bicaudal-C family of RNA binding proteins. We suggest that GLD-2
      is the prototype for a class of regulatory cytoplasmic PAPs that are recruited to
      specific mRNAs by a binding partner, thereby targeting those mRNAs for
      polyadenylation and increased expression.

PMID- 12239572
TI  - Forkhead transcription factor FOXO3a protects quiescent cells from oxidative
      stress.
AB  - Reactive oxygen species are required for cell proliferation but can also induce
      apoptosis. In proliferating cells this paradox is solved by the activation of
      protein kinase B (PKB; also known as c-Akt), which protects cells from apoptosis.
      By contrast, it is unknown how quiescent cells that lack PKB activity are
      protected against cell death induced by reactive oxygen species. Here we show
      that the PKB-regulated Forkhead transcription factor FOXO3a (also known as FKHR
      L1) protects quiescent cells from oxidative stress by directly increasing their
      quantities of manganese superoxide dismutase (MnSOD) messenger RNA and protein.
      This increase in protection from reactive oxygen species antagonizes apoptosis
      caused by glucose deprivation. In quiescent cells that lack the protective
      mechanism of PKB-mediated signalling, an alternative mechanism is induced as a
      consequence of PKB inactivity. This mechanism entails the activation of Forkhead
      transcription factors, the transcriptional activation of MnSOD and the subsequent
      reduction of reactive oxygen species. Increased resistance to oxidative stress is
      associated with longevity. The model of Forkhead involvement in regulating
      longevity stems from genetic analysis in Caenorhabditis elegans, and we conclude
      that this model also extends to mammalian systems.

PMID- 12239573
TI  - Reducing bacterial counts in dental unit waterlines: tap water versus distilled
      water.
AB  - BACKGROUND: The maximum recommended level of microbial contamination of water
      from dental unit waterlines (DUWL) is 200 colony-forming units per milliliter
      (CFU/mL). This article addresses the importance of water selection in achieving
      that standard. METHODS: Microbial contamination in water samples from 75 new
      dental units, with a closed-circuit water system, were compared using
      combinations of tap water and sterile distilled water with and without two
      chemical disinfectants (bleach and 0.12% chlorhexidine gluconate, Bio2000) over a
      six-week period. Baseline tap water samples were collected and tested initially.
      RESULTS: The microbial plate counts of seven tap water specimens (controls)
      ranged from 4 to 95 CFU/mL. These results were well below both the 500 CFU/mL
      standard for public drinking water and the 200 CFU/mL goal for dental treatment
      water. However, when passed through dental units, no significant bacterial
      reduction was achieved for samples of tap water (Group 1), tap water treated with
      bleach (Group 2), or tap water treated with Bio2000 (Group 4). Only water samples
      from dental units using Bio2000 alone (Group 3) or a combination of sterile,
      distilled water with Bio2000 (Group 5) met or exceeded the 200 CFU/mL standard.
      CONCLUSIONS: Using tap water alone or tap water with bleach did not improve water
      quality. However, the American Dental Association (ADA) standard for reduced
      microbial contamination of dental unit waterlines was met using Bio2000 and
      distilled water treated with Bio2000. CLINICAL SIGNIFICANCE: The ADA standard of
      200 CFU/mL was achieved using a closed water system and distilled water treated
      with Bio2000. Using 100% Bio2000 is also effective, but more costly.

PMID- 12239574
TI  - Evidence-based decision making in action: Part 1--Finding the best clinical
      evidence.
AB  - The purpose of this article is to introduce evidence-based concepts and
      demonstrate how to find valid evidence to answer clinical questions. Evidence
      based decision making (EBDM) requires understanding new concepts and developing
      new skills including how to: ask good clinical questions, conduct a computerized
      search, critically appraise the evidence, apply the results in clinical practice,
      and evaluate the process. This approach recognizes that clinicians can never be
      completely current with all conditions, medications, materials, or available
      products. Thus EBDM provides a mechanism for addressing these gaps in knowledge
      in order to provide the best care possible. In Part 1, a case scenario
      demonstrates the application of the skills involved in structuring a clinical
      question and conducting an online search using PubMed. Practice tips are provided
      along with online resources related to the evidence-based process.

PMID- 12239575
TI  - The effect of Salvadora persica extract (miswak) and chlorhexidine gluconate on
      human dentin: a SEM study.
AB  - Bacterial plaque is solely responsible for the initiation and progression of
      periodontal diseases. There are different mechanical and chemical methods
      available for the maintenance of oral health through plaque control. Toothbrushes
      and miswak (chewing sticks) are widely used for the mechanical removal of plaque.
      Chlorhexidine gluconate (CHX) is one of the best-proven anti-plaque agents. The
      aim of this study was to evaluate the effects of CHX and miswak extract on
      healthy and periodontally involved human dentin. Sixteen human premolars recently
      extracted for orthodontic and periodontal reasons were used in the study. Teeth
      were free from caries, cervical restorations, or erosions. The dentin disc
      specimens were prepared and half of them were etched with 6% citric acid for 120
      sec. Both etched and unetched were further treated with CHX and 50% miswak
      extract and prepared for Scanning Electron Microscopic (SEM) examination. It was
      concluded that CHX 0.2% and miswak extract 50% had a similar effect on dentin in
      the control group. Miswak extract removed more smear layer as compared to CHX.
      Further research is needed in vivo to compare the effects of CHX and miswak
      extract on periodontally involved teeth and teeth with dentinal hypersensitivity.

PMID- 12239576
TI  - Mentoring: a professional responsibility.
AB  - Dental and dental hygiene students were surveyed to determine how many students
      had participated in high school or college career exploration courses
      sponsored/supported by Oregon Health & Science University (OHSU) School of
      Dentistry. The participants were asked to identify which aspects of the programs
      were the most influential in shaping their exploration of a dental or dental
      hygiene career and why they decided to apply to the dental or dental hygiene
      program. These aspects included the availability and the cost of the courses,
      lecture content, hands-on activities in the laboratory, observations in dental
      offices, mentoring activities of dentists, dental hygienists, dental/dental
      hygiene students, and perceived value for applicant competitiveness. The faculty
      evaluated their level of participation in relation to teaching responsibilities
      and time commitment. An analysis of the direct and indirect costs to the school
      was examined. Results of the surveys indicated that between 20-42% of the
      entering classes had participated in one or more career exploration activities or
      programs. Participants identified mentoring relationships with their current
      dentist and dental hygienist as the most important factor in determining their
      decision to choose dentistry or dental hygiene as a career. Observations in
      dental offices, encouragement from a dental and/or dental hygiene student, hands
      on activities, and repetitive positive career experiences were also significant
      factors.

PMID- 12239577
TI  - White plaque of the lateral tongue.
AB  - A healthy 48-year old white woman presented with a chief complaint of an
      'irritated' sensation involving her tongue. The problem seemed to be limited to
      her left lateral tongue and had been noticed for at least six months by the
      patient. She also indicated the condition varied in severity.

PMID- 12239578
TI  - Submitting dental insurance claims.

PMID- 12239579
TI  - RNA-mediated gene regulation system: now and the future (Review).
AB  - The discovery of RNA-mediated gene regulation system has brought human beings
      another big surprise on the wisdom and power of nature. Nature can not only
      create genetic codes with 4 nucleotides and produce proteins with 21 amino acids,
      but also control their intermediates, mRNAs, with double-stranded RNA molecules
      composed of approximately 22 nt. It has been clear that approximately 22 nt
      dsRNAs can specifically and efficiently modulate gene expression through sequence
      specific targeting thus silencing of RNA. This system promises to be an excellent
      model for the identification of gene functions and the exploitation of gene
      expression and phenotype alteration, and a promising way for the prevention and
      treatment of human diseases.

PMID- 12239580
TI  - Hirschsprung, RET-SOX and beyond: the challenge of examining non-mendelian traits
      (Review).
AB  - Hirschsprung disease (HSCR), or congenital intestinal aganglionosis, is a common
      hereditary disorder causing intestinal obstruction, thereby showing considerable
      phenotypic variation in conjunction with complex inheritance. Moreover,
      phenotypic assessment of the disease has been complicated since a subset of the
      observed mutations is also associated with several additional syndromic
      anomalies. Coding sequence mutations in e.g. RET, GDNF, EDNRB, EDN3, and SOX10
      lead to long-segment (L-HSCR) as well as syndromic HSCR but fail to explain the
      transmission of the much more common short-segment form (S-HSCR). Furthermore,
      mutations in the RET gene are responsible for approximately half of the familial
      and some sporadic cases, strongly suggesting, on the one hand, the importance of
      non-coding variations and, on the other hand, that additional genes involved in
      the development of the enteric nervous system still await their discovery. For
      almost all of the identified HSCR genes incomplete penetrance of the HSCR
      phenotype has been reported, probably due to modifier loci. Therefore, HSCR has
      become a model for a complex oligo-/polygenic disorder in which the relationship
      between different genes creating a non-mendelian inheritance pattern still
      remains to be elucidated.

PMID- 12239581
TI  - Molecular analysis of TGF-(beta)s and their receptors in human keratinocyte cell
      lines of different biological behaviour.
AB  - We investigated three clonally related human keratinocyte cell lines of different
      biological behaviour, HaCaT (non-tumorigenic), A5 (benign, tumorigenic) and II
      4RT (malignant, tumorigenic), with regard to the expression of TGF-beta-isoforms 
      1, -2 and -3 and that of the TGF-beta-cell-receptors TBR-I, -II and -III. In
      addition, we amplified and sequenced the genome of TBR-II which is known to be a
      target for mutations in several types of malignant tumors including squamous cell
      carcinomas. In all three cell lines, TGF-beta1 and -beta3 were present only in
      very low amounts. Western blots provided no evidence for differences in TGF-beta1
      between the cell lines. However, in immunohistochemistry more cells were slightly
      positive for this cytokine in HaCaT than in A5 and II-4RT cells. In contrast, a
      significantly variable expression of TGF-beta2 was seen by both Western blot and
      immunohistochemistry. Thereby, the non-tumorigenic HaCaT-cells contained
      significantly more TGF-beta2 than the tumorigenic, benign A5 cells and the
      malignant II-4RT cells. TBR-I, -II and -III were present in all three cell lines.
      While most cells were positive for TBR-I, only part of the cells contained TBR-II
      and -III, however, without obvious differences between the three cell lines. The
      molecular analysis of all 7 exons of TBR-II by PCR amplification and direct
      sequencing revealed in all three cell lines correct sequences without evidence
      for mutations. Our study indicates differences in the expression of TGF-beta in a
      human model of keratinocytes of varying tumorigenicity, but presents no evidence
      for mutations in the functionally most important TGF-beta-receptor TBR-II. This
      suggests a dysregulation of cytokine control on the level of TGF-beta expression,
      which may be responsible for the biological behaviour.

PMID- 12239582
TI  - Role of endogenous regucalcin in bone metabolism: bone loss is induced in
      regucalcin transgenic rats.
AB  - The role of endogenous regucalcin in the regulation of bone metabolism was
      investigated by using regucalcin transgenic (TG) rats. The expression of
      regucalcin mRNA in the femoral-diaphyseal and -metaphyseal tissues of normal
      (wild-type) rats was shown by using reverse transcription-polymerase chain
      reaction (RT-PCR) with a specific primer of regucalcin cDNA. Regucalcin protein
      was detected in the femoral-diaphyseal and -metaphyseal tissues of normal (wild
      type) rats using Western analysis. Regucalcin levels were significantly increased
      in the femoral-metaphyseal tissues of regucalcin TG male rats and in the
      diaphyseal and metaphyseal tissues of the TG female rats. The morphologic change
      in the femoral-diaphyseal and -metaphyseal tissues of regucalcin TG rats was
      demonstrated by using a peripheral quantitative computed tomography (pQCT);
      morphologic change was great in the femoral tissues of female rats as compared
      with that of male rats. Mineral content, mineral density and polar strength
      strain index in the femoral-diaphyseal and -metaphyseal tissues were markedly
      reduced in regucalcin TG female rats. A significant decrease in cortical
      thickness was seen in the femoral diaphysis of regucalcin TG female rats. Calcium
      content in the femoral-diaphyseal and -metaphyseal tissues was significantly
      decreased in regucalcin TG male and female rats; a remarkable decrease was seen
      in female rats. Femoral-metaphyseal alkaline phosphatase activity was
      significantly lowered in regucalcin TG female rats. The enzyme activity was not
      significantly changed in the femoral-diaphyseal tissues of the TG female rats. In
      the diaphyseal tissue of male rats, the enzyme activity was significantly
      decreased in the TG rats. A significant decrease in deoxyribonucleic acid (DNA)
      content was seen in the metaphyseal tissue of regucalcin TG male rats and in the
      diaphyseal and metaphyseal tissues of the TG female rats. This study demonstrates
      that bone loss is induced in the femoral tissue of regucalcin transgenic rats,
      and that a remarkable decrease in bone morphologic index and biochemical
      component was seen in the female rats. Regucalcin may be involved in the
      regulation of bone metabolism.

PMID- 12239583
TI  - Enhanced ability of the progenipoietin-1 to suppress apoptosis in human
      hematopoietic cells.
AB  - Repopulating hematopoietic cell compartments after myeloablative chemotherapy
      remains a key factor in a successful chemotherapy program. Modified and chimeric
      cytokines have been developed to help reduce inflammation, fever and
      hospitalization time for patients. A chimeric cytokine, progenipoietin-1 (ProGP
      1), containing the G-CSF and FL receptor agonists binds both the G-CSF receptor
      and FLT-3. It also stimulates the growth of dendritic cells, which play an
      important role in immunotherapy. While in vivo effects of ProGP-1 are well
      described, the mechanisms by which it stimulates growth are not well understood.
      We have investigated the effects of ProGP-1 on prevention of apoptosis in the
      human hematopoietic cell line OCI-AML.5. ProGP-1 promoted cellular proliferation
      better than G-CSF or FL separately but stimulated proliferation similar to their
      co-addition as demonstrated by growth curves and [3H]-thymidine incorporation.
      ProGP-1 prevented apoptosis to a greater degree than G-CSF or FL alone as
      determined by annexin V/propidium iodide binding and TUNEL assays. ProGP-1
      promoted maintenance of the mitochondrial membrane potential better than G-CSF or
      FL alone. In addition, Pro-GP promoted a lower redox potential as higher levels
      of free radicals were detected after cytokine treatment than in cytokine-deprived
      cells implying increased respiration. These data indicate that ProGP-1 promotes
      the proliferation and prevents the apoptosis of human hematopoietic cells better
      than FL or G-CSF alone, and to a similar extent as their co-addition. Thus, ProGP
      1 can be used to repopulate certain hematopoietic cells as a single entity rather
      than the introduction of two different cytokines.

PMID- 12239584
TI  - Codon 45 of the beta-catenin gene, a specific mutational target site of Wilms'
      tumor.
AB  - Wilms' tumor (WT) is the most common childhood renal malignancy. Although several
      genetic loci such as the WT1 gene have been known to relate to the biology of WT,
      the cause of the tumor is complex and the implicated molecular pathways are
      largely unknown. The beta-catenin gene encodes a protein playing an important
      role in the Wnt signaling pathway, and its mutations that abrogate specific
      serine/threonine phosphorylation sites and express oncogenic effect have been
      found in a variety of tumors. Implication of beta-catenin mutations in WT was
      investigated in 24 tumors collected from 20 WT patients. One patient had a total
      of five multiple tumors simultaneously in the bilateral kidneys. Exon 3 and its
      flanking regions encompassing mutational hot spots of the gene were examined by
      PCR-based methods. Samples indicating to harbor mutations were further analyzed
      by sequencing. Six tumors (6/24, 25%) from 4 patients (4/20, 20%) were confirmed
      to have mutations in heterozygous status. All the mutations, including five
      different types, were uniformly observed at codon 45 (Ser). Three mutations,
      Ser45Phe (TCT --> TTT), Ser45Tyr (TCT --> TAT), and Delta45 (deletion of TCT),
      were found in 3 of 19 unilateral WTs. Other three mutations were detected in
      three of five multiple tumors developed in the bilateral WT patient; a mutation
      of Delta45 in one of two tumors in the right kidney, and Ser45Cys (TCT --> TGT)
      and Ser45Pro (TCT --> CCT) in two of three tumors in the left kidney. Frequent
      beta-catenin mutations preferentially occurring at codon 45 most likely indicate
      special importance of this codon for the development of WT and existence of an
      underlying mechanism causing such a tissue-specific mutational pattern.

PMID- 12239586
TI  - Effects of blue-light-exposure on growth of extracorporeally circulated leukemic
      cells in rats with leukemia induced by 1-ethyl-1-nitrosourea.
AB  - To explore the possibility of using blue light for extracorporeal circulation
      therapy in patients with leukemia, the effects of blue light on cell growth in
      vitro and in extracorporeally circulated blood of rats with leukemia were
      evaluated. When HL60 cells circulated extracorporeally using a peristaltic pump
      were exposed to blue light for 5 h, the growth of the cells was found to be
      markedly suppressed. Then, the blood of rats with erythroblastic leukemia,
      induced by the administration of tap water containing l-ethyl-l-nitrosourea (ENU)
      for 9-16 weeks, was circulated extracorporeally and exposed to blue light for 3
      h. Lymphocytes were separated from the peripheral blood immediately after the end
      of blue-light-exposure and incubated for 7 days. The growth of leukemic cells was
      found to be significantly suppressed following exposure to blue light, whereas
      the growth of normal lymphocytes was unaffected. These findings suggest that
      cancer cells may be more sensitive to blue light than normal cells.

PMID- 12239585
TI  - Evidence for an autocrine-paracrine role of adrenomedullin in the cultured rat
      adrenal zona glomerulosa cells.
AB  - Rat adrenomedullin (ADM) is a 50-amino acid hypotensive and vasodilating peptide,
      which derives from the posttranslational proteolytic cleavage of pro(p)ADM. ADM
      acts via at least two subtypes of receptors, named L1-receptor (L1-R) and
      calcitonin receptor-like receptor (CRLR). CRLR functions as a calcitonin gene
      related peptide or a selective ADM receptor depending on the expression of the
      subtype 1 or the subtypes 2 and 3 of a family of receptor-activity-modifying
      proteins (RAMPs). Adrenal zona glomerulosa (ZG) is one of the main target tissues
      of ADM, which has been shown to exert a potent inhibitory effect on aldosterone
      secretion acting through ADM[22-52]-sensitive receptors. Reverse transcription
      (RT)-polymerase chain reaction (PCR) consistently allowed the detection of pADM
      mRNA in the ZG, but not zona fasciculata-reticularis (ZF/R) cells of the rat
      adrenal cortex. Immunocytochemistry and radioimmune assay showed a weak but
      sizeable expression of ADM protein in the ZG, but not inner adrenocortical
      layers. ZG cells expressed peptidyl-glycine alpha-amidating monooxigenase, the
      enzyme converting immature ADM to the mature peptide, thereby suggesting their
      potential ability to produce active ADM. RT-PCR demonstrated the presence in ZG,
      but not ZF/R cells, of the specific mRNAs of L1-R, CRLR and RAMPs (especially
      RAMP2). ZG cells were cultured in vitro for 24 or 48 h in the presence of ADM
      (10(-8) M) and/or its receptor antagonist ADM[22-52] (10(-6) M). ADM increased
      proliferation index and lowered apoptotic index of cultured cells, and the
      effects were annulled by ADM[22-52]. ADM[22-52] alone was ineffective in 24 h
      cultures, but moderately decreased proliferation index and raised apoptotic index
      in 48 h cultures. In conclusion, our study provides evidence that i) rat ZG cells
      express ADM and ADM receptor of L1 and CRLR/RAMP2 subtypes, which both are
      sensitive to ADM[22-52]; and ii) endogenous ADM system modulates in an
      autocrine/paracrine manner ZG growth, by stimulating cell proliferation and
      reducing cell apoptotic deletion.

PMID- 12239587
TI  - Communication between animal cells and the plant foods they ingest: phyto-zooidal
      dependencies and signaling (Review).
AB  - The beneficial effect of plant foods on human health is unmistakable. Time and
      time again, studies have found foods of plant origin to reduce the risk of most
      major chronic illnesses suffered by the human population. Possible mechanisms for
      the preventative effects of these foods are discussed. Each of the plant groups
      reviewed was found to reduce the risk of one or more of the following:
      cardiovascular disease, cancer (lung, breast, colon, rectal, prostate,
      epithelial, stomach, esophageal, oral, pharynx, larynx, urinary tract,
      endometrium, pancreas, thyroid, liver, ovary, gallbladder, bladder, and kidney),
      diabetes, hypertension, bone degeneration, diverticulitis, constipation,
      gallstones, age-related blindness. Almost no evidence was found to suggest a
      negative effect on health due to consumption of these plant foods. Based on this
      material and a review of conserved animal signaling molecules we surmise that
      animals require these chemicals to enhance specific mammalian cellular processes,
      demonstrating phyto-zooidal signaling. Further, this diet dependency coupling
      between plants and animals probably evolved because of the abundance of a
      particular plant material in a local environment, which is now broken because of
      technological advances. In conclusion, the overwhelming majority of evidence
      shows that people may significantly decrease their risks of the aforementioned
      diseases by increasing their intake of these foods since they represent a natural
      method to enhance animal processes and signaling.

PMID- 12239588
TI  - Angiopoietin-1 and vascular endothelial growth factor expression in human
      esophageal cancer.
AB  - Angiopoietin-1 (Ang-1) has been shown to act as an angiogenic promoter in
      embryonic angiogenesis by promoting vascular branching, pericyte recruitment and
      endothelial survival. Ang-1 expression has not been examined in human esophageal
      cancer. We examined Ang-1 and vascular endothelial growth factor (VEGF) gene
      expression in tumors from 45 esophageal cancer patients who underwent surgical
      resection. Forty (88.9%) of the 45 esophageal cancers revealed Ang-1 gene
      expression. VEGF121, VEGF165 and VEGF189 isoforms were detected in 93.3 (42/45),
      55.6 (25/45) and 26.7% (12/45) of the cases, respectively. Ang-1 gene expression
      was significantly correlated with VEGF121 and VEGF165 gene expression (P=0.0289
      and P=0.0127, respectively, Fisher's test). The results suggest that Ang-1 is
      associated with neovascularization in the cancer stroma through VEGF net-works in
      esophageal cancer.

PMID- 12239589
TI  - Efficacy of chemopreventive agents for growth inhibition of Apc [+/-] 1638NCOL
      colonic epithelial cells.
AB  - Germline mutations of the Apc tumor suppressor gene result in increased risk for
      gastrointestinal carcinogenesis. The Apc1638N [+/-] mouse exhibits accelerated
      gastrointestinal carcinogenesis that is modifiable by select pharmacological and
      dietary agents. Experiments in the present study were conducted on a
      subculturable epithelial 1638NCOL cell line established from histologically
      normal colon of Apc1638N [+/-] mouse to examine the effects of selected
      chemopreventive agents that differ in their mechanism of action. Extent of growth
      arrest, number of cell population doublings, cell cycle progression and aneuploid
      G0/G1: S + G2/M ratio represented the quantitative endpoints for the
      susceptibility and efficacy of chemopreventive agents. Treatment of exponentially
      growing 1638NCOL cells with maximum cytostatic dose of 9cisRA, DFMO or SUL (100
      microM) produced a 60-70% growth arrest, that with TAM and AMF (10 microM)
      produced a 20-40% growth arrest, while that with OLT (100 microM) produced a 25%
      growth arrest. This response was associated with corresponding decrease in the
      number of cell population doubling. 9cisRA, SUL or AMF increased the aneuploid
      G0/G1: S + G2/M ratio by inducing G1 checkpoint arrest, while DFMO, TAM and OLT
      decreased the ratio by inducing G2 checkpoint arrest. Thus, cell cycle phase
      dependent susceptibility of the Apc [+/-] 1638NCOL cell line to mechanistically
      distinct chemopreventive agents validates a novel colon epithelial cell culture
      model for mechanistic, preventive or therapeutic studies on Apc regulated colon
      carcinogenesis.

PMID- 12239590
TI  - Significance of heme oxygenase in prolactin-mediated cell proliferation and
      angiogenesis in human endothelial cells.
AB  - Our objectives were to determine whether heme oxygenase-1 is a second messenger
      for prolactin-mediated angiogenesis. Endothelial cell proliferation and
      angiogenesis assay demonstrated that cell number and capillary formation were
      increased by prolactin (10 and 25 ng/ml). Both protein synthesis and mRNA
      analysis confirmed that HO-1 expression was induced by prolactin in cultured
      endothelial cells and occurred in a concentration-dependent manner. Endothelial
      cells transduced with retrovirus-mediated delivery of HO-1 gene in sense and
      antisense orientation were used to further determine whether HO-1 overexpression
      or underexpression modulated prolactin-mediated endothelial cell proliferation
      and angiogenesis. Incubation of human microvessel endothelial cells transduced
      with HO-1 in sense orientation resulted in enhancement of prolactin-mediated
      increase in endothelial cell proliferation and angiogenesis, whereas inhibition
      of HO-1 by transduction of HO-1 in antisense orientation prevented prolactin
      increase in endothelial cell proliferation. Similarly, addition of stannic
      mesoporphyrin, the inhibitor of HO activity, prevented PRL-mediated increase in
      endothelial cell proliferation. Our results demonstrated for the first time, that
      prolactin-mediated angiogenesis and cell proliferation was dependent on HO-1 gene
      expression.

PMID- 12239591
TI  - Urinary soluble CD14 mediates human proximal tubular epithelial cell injury
      induced by LPS.
AB  - Renal proximal tubular epithelial cells (PTEC) are target for LPS during sepsis
      and renal infections. In the present study, we evaluated whether stimulation of
      human PTEC by LPS is modulated through the soluble or the membrane form of the
      LPS receptor CD14. We found that PTEC lacked expression of the membrane form of
      CD14 and did not release soluble CD14 (sCD14). sCD14 was detected in the urine of
      normal subjects and it was increased in patients with renal sepsis or with
      proteinuria. In the presence of sCD14 and LPS binding protein (LBP), PTEC were 10
      to 100-fold more sensitive to LPS activation, resulting in cytokine production
      (IL-6, IL-8 and TNF-alpha) and NO release. We found that sCD14 purified from
      urine was biologically active on PTEC. Moreover, the presence of sCD14 and LBP
      was required for cytotoxicity induced by low concentrations of LPS (1-10 ng/ml)
      in PTEC. Cell death showed the characteristics of both necrosis and apoptosis, as
      demonstrated by LDH release and by TUNEL and acridine orange staining and caspase
      3 activation. Whereas the LPS alone was sufficient to induce necrosis, sCD14 and
      LBP were required for apoptosis. Our results suggest that sCD14 excreted in urine
      may participate with endotoxin in the activation and injury of renal proximal
      tubules. In particular, sCD14 may contribute to the tubulo-interstitial injury in
      clinical settings characterised by proteinuria and enhanced susceptibility to
      infections such as in diabetes.

PMID- 12239592
TI  - Effects of prostaglandins E1 and E2 on the growth and differentiation of
      osteoblast-like cells cultured in vitro.
AB  - Prostaglandins E (PGEs) are abundantly produced in the skeletal tissue, the
      turnover of which they can modulate acting on both bone deposition and
      resorption. We compared the effects of PGE1 and PGE2 on the growth and
      differentiation of rat bone-marrow osteoblast-like cells cultured in vitro. Both
      PGEs stimulated cultured cell growth, PGE2 being more effective than PGE1. PGE1
      inhibited and PGE2 enhanced alkaline phosphatase activity. Both PGEs markedly
      raised osteocalcin synthesis, without apparently affecting collagenase-digestible
      protein production. Scanning electron microscopy showed that untreated cultured
      osteoblast-like cells were arranged in clusters and displayed a polygonal shape.
      PGE1 did not alter cell morphology, while PGE2 provoked elongation of cultured
      cells and sprouting of slend cytoplasmic processes. Morphometric analysis
      indicated that PGE1 decreased and PGE2 increased cultured-cell dimensions.
      Collectively, these findings allow us to conclude that PGE1 and PGE2, although
      being both able to enhance proliferation of osteoblast-like cells cultured in
      vitro, exert divergent effects on their differentiation. PGE1 seems to slow-down
      osteoblast maturation, while PGE2 appears to stimulate osteoblast differentiation
      to mature osteocytes.

PMID- 12239593
TI  - Significance of brain natriuretic peptides in patients on continuous ambulatory
      peritoneal dialysis.
AB  - It is well known that plasma brain natriuretic peptide (BNP) concentration is
      elevated in cardiovascular diseases such as congestive heart failure. However,
      although it has been reported to increase in hemodialysis (HD) patients, little
      is known about plasma BNP in patients undergoing continuous ambulatory peritoneal
      dialysis (CAPD). Plasma BNP concentrations were measured and compared among CAPD
      patients (n=32), HD patients (n=63) and healthy volunteers (n=14) as well as
      those patients without cardiovascular disease. In addition, the correlation
      between plasma BNP concentration and parameters of echocardiography was examined.
      Plasma BNP concentration was significantly higher in CAPD patients without
      cardiovascular disease (n=23) than in healthy volunteers (n=14) (62.1+/-60.6
      pg/ml versus 9.7+/-9.7 pg/ml, mean +/- SD, P<0.0001). Furthermore, it had a
      positive correlation with LVMI (CAPD: r=0.37, P=0.0354; HD: r=0.49, P<0.0001) but
      a negative correlation with LVEF (CAPD: r=-0.39, P=0.0277; HD: r=-0.40, P=0.0010)
      in both CAPD and HD patients. When all patients were compared, plasma BNP
      concentration was significantly lower in CAPD patients (n=32) than in HD patients
      (n=63) (114.8+/-142.7 pg/ml versus 296.8+/-430.4 pg/ml, P<0.0001). When those
      patients without cardiovascular disease was compared, it was also significantly
      lower in CAPD patients (n=23) than in HD patients (n=40) (62.1+/-60.6 pg/ml
      versus 151.8+/-102.2 pg/ml, P<0.0001). In conclusion, plasma BNP concentration
      was elevated in CAPD patients and correlated with LVMI and LVEF, suggesting that
      plasma BNP in CAPD patients may be associated with left ventricular hypertrophy
      (LVH) and left ventricular systolic dysfunction. In addition, plasma BNP
      concentration was significantly lower in CAPD patients than in HD patients,
      suggesting that cardiac load in CAPD patients may be lower than that of HD
      patients.

PMID- 12239594
TI  - Induction of cell arrest by transfection of macrophage migration inhibitory
      factor antisense plasmid.
AB  - Macrophage migration inhibitory factor (MIF) is known to be a proinflammatory
      cytokine, glucocorticoid-induced immunomodulator. MIF is abundantly expressed in
      various cancer cells, and is considered to contribute to cell growth and
      differentiation. MIF inactivates the functions of wild-type p53. Consequently, if
      MIF expression in cancer cells can be suppressed, the functions of p53 and p21
      will be restored and an anti-tumor effect can be expected due to the inducement
      of cell cycle arrest. In the p21 promoter there are three DNA binding sites of
      STAT-1, and p21 is induced without p53. In the present study, an investigation
      was made of associations between p53-p21 and STAT-1-p21 signal transmission by
      the introduction of antisense MIF plasmid and cell cycle. Two groups, namely a
      transfected antisense MIF plasmid group (antisense MIF group) and a transfected
      PBK group (PBK group, as a control), in a DLD-1 cell line were created and used
      in these experiments. The cell cycle, apoptosis, inhibition of growth by
      subcutaneous tumor, p21 promoter activity, p21 protein, p53 cis enhancer activity
      and STAT-1 protein were observed. In the antisense MIF group, a shift from the S
      phase to the G1 phase and an inhibition of growth was noted. Scarcely any
      apoptotic cells were noted in either group. In terms of p21 promoter, p53 cis
      enhancer and STAT-1 activity, an increase in activity was found in the anti-sense
      MIF group. In cancer cells with MIF expression, cell arrest via p21 began due to
      the inhibition of MIF expression, and increases in p53 transcription activity and
      in STAT-1 intervention at this time were confirmed.

PMID- 12239595
TI  - Response of peripheral blood mononuclear cells in hemodialyzed patients against
      endotoxin and muramyldipeptide.
AB  - Microbial fragments of endotoxin (ET) and peptidoglycan (PG) are recognized as
      pyrogen in dialysate. The aim of this study was to evaluate the effect of
      contaminated dialysate on peripheral blood mononuclear cells (PBMC) in
      hemodialyzed patients by measuring production of interleukine 1-beta (IL-1beta)
      in vitro. Venous blood was withdrawn before dialysis session. The effects of a
      dialysis membrane, a magnitude of dialysate contamination and a duration of
      hemodialysis were studied. PBMC was stimulated by the addition of water
      containing either ET or muramyldipeptide (MDP), the minimum biological activated
      fragment of PG, or ET+MDP. IL-1beta production of PBMC stimulated by ET or ET+MDP
      in patients on hemodialysis using a polysulfon (PS) membrane was significantly
      lower than those using a cuprammonium-rayon (CU) membrane, ethylenevinylalcohol
      (EVAL) membrane, polymethylmetacrylate (PMMA) membrane, respectively. Among
      patients on the PS membranes, those who were exposed to dialysate with higher
      pyrogen contamination had lower PBMC cytokine production than those dialyzed with
      ultrapure dialysate. Response of PBMC in patients against ET+MDP stimulant
      decreased with duration of dialysis treatment. This suggested that chronic
      exposure to ET or MDP during hemodialysis treatment, might cause a tolerance
      against ET and ET+MDP in PBMC.

PMID- 12239596
TI  - The HMG-CoA reductase inhibitor lovastatin protects cells from the antineoplastic
      drugs doxorubicin and etoposide.
AB  - Ras-homologous GTPases are involved in the regulation of genotoxic stress-induced
      gene expression and cell death. Since they need C-terminal isoprenylation for
      correct intracellular localization and function, we investigated whether
      depletion of cells from isopren precursor moieties using the HMG-CoA reductase
      inhibitor lovastatin affects cellular sensitivity to DNA damaging drugs. Here we
      show that lovastatin renders cells highly resistant to the tumor-therapeutic
      compound doxorubicin. Desensitization by lovastatin was reverted by co-treatment
      with GGPP indicating that inhibition of protein geranylgeranylation is involved
      in acquired doxorubicin resistance. Lovastatin does not influence cellular
      sensitivity to DNA damaging compounds such as cisplatin, methyl methanesulfonate
      and ionizing radiation. The frequency of apoptotic cell death induced by
      doxorubicin was not affected by lovastatin as shown by both annexin V and DNA
      fragmentation assay. However, lovastatin releases cells from doxorubicin induced
      G2 blockage. Furthermore, lovastatin protects cells from doxorubicin-induced DNA
      strand breakage without affecting drug uptake or the expression of multidrug
      resistance protein (mdr-1). Since lovastatin confers cross-resistance to the
      topoisomerase II specific inhibitor etoposide, we suggest desensitization by the
      statin to be related to topoisomerase II function. The finding that lovastatin
      renders cells resistant to doxorubicin and etoposide by reducing their genotoxic
      and cytotoxic effects might have clinical implications for cancer therapy.

PMID- 12239597
TI  - Influence of allergen-specific immunotherapy on IL-4-dependent IL-12 production
      by monocytes.
AB  - Allergen-specific immunotherapy (AIT) is an effective method of allergy
      treatment. Reduction of allergy symptoms followed by AIT presumably depends on
      modification of cytokine production, especially of IFN-gamma and/or IL-4.
      Previously, we found that lower IL-12 production by allergic monocytes than in
      healthy control, could depend on higher IL-4 receptor alpha-chain (CD124)
      expression. Since IFN-gamma production is stimulated by IL-12, which in turn is
      down-regulated by IL-4, the aim of study was to analyze the influence of AIT on
      the network of these cytokines. Moreover, we estimated the possible role of CD124
      in that process. Patients (n=16) with grass pollen allergy were subjected to AIT
      with Allergovit for 5 to 6 weeks. The clinical examination and blood analyses
      were performed before and after AIT. Clinical improvement in course of AIT was
      rather weak, however, we found significant increase of mean IFN-gamma production
      by PBMC. Although the increase of mean IL-12 production by monocytes following
      AIT was non-significant, we observed statistically significant decrease of
      monocyte sensitivity to IL-4 suppressed IL-12 production. Flow cytometry analysis
      revealed significant decrease of CD124 expression on monocytes after AIT. Despite
      unchanged mean IL-4 level the decrease of CD124 expression after AIT could
      explain the decreased monocyte sensitivity to IL-4 and its role in further IL-12
      and IFN-gamma tuning.

PMID- 12239598
TI  - Direct hemoperfusion by using Lixelle column for the treatment of systemic
      inflammatory response syndrome.
AB  - We have previously reported that Lixelle which was used for beta2-microglobulin
      (BMG) adsorption column could adsorb not only BMG but also inflammatory cytokines
      and microbial fragments such as endotoxin (ET) and peptidoglycan (PG). The aim of
      this study was to estimate that an adsorbent column was used in direct
      hemoperfusion in patients clinically having systemic inflammatory response
      syndrome (SIRS), and the relationship between a decrease in cytokines and
      clinical course was examined. Meanwhile, as regards in vivo rate of removing
      cytokine based on pre-treatment cytokine concentration versus pre-column
      concentration at the time of evaluation, it increased with lapse of time, and the
      removing rate was 40% with 4 h direct hemoperfusion by using the Lixelle column
      in some of the patients. As to in vivo rates of adsorbing IL-1beta, IL-1Ra, IL-6,
      IL-8 and TNF-alpha before and after the use of column at the time of evaluation,
      the rates 5 min after the start were 31.4, 39.3, 36.4, 76.2 and 71.6%
      respectively. Clinically, it was possible to increase blood pressure and recover
      from shock status. With the use of this column, removal of inflammatory cytokine
      by adsorption can be expected. Thus, it can be applied to the treatment of
      hypercytokinemia.

PMID- 12239599
TI  - Alteration in expression of polyamine and glucose-related enzyme mRNA after small
      bowel resection in the rat residual ileum.
AB  - The adaptive hyperplasia of the residual intestine after a massive bowel
      resection is not fully understood. We investigated the alterations in polyamine
      and glucose-related enzyme mRNA expression during intestinal adaptation. Six-week
      old male Wistar rats underwent an 80% resection of the small intestine. The
      residual ileum was removed on the preoperative day (control) and on postoperative
      day (POD) 1, 3, 5 and 7. The total RNA was extracted from the mucosa, and a
      Northern blot analysis was performed. In the residual small intestine, the
      expression of polyamine synthesis enzymes, ornithine decarboxylase (ODC) and S
      adenosylmethionine decarboxylase (SAMDC) mRNAs were increased on POD 1. The
      expression of polyamine degradation enzymes diamine oxidase (DAO) and
      spermidine/spermine N1-acetyltransferase (SSAT) mRNA did not change dramatically.
      Antizyme-1 (AZ-1) mRNA was significantly increased on POD 1. The mRNA expression
      of glucose absorption and metabolism-related proteins, including the Na+
      dependent D-glucose cotransporter (SGLT1), fructose-6-phosphate,2-kinase/fructose
      2,6-bisphosphatase (Fru-6-P,2-kinase/Fru-2,6-Pase) and glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) were only slightly changed on POD 1. The enzymes
      responsible for polyamine biosynthesis but not catabolism were upregulated at the
      translational level in enterocytes after a small bowel resection. The expression
      of glucose transport and glycolysis enzyme mRNAs did not increase after a small
      bowel resection.

PMID- 12239600
TI  - Myristoyl-CoA:protein N-myristoyltransferase: a novel molecular approach for
      cancer therapy (Review).
AB  - Colorectal cancer is the second leading cause of malignant death, and better
      preventive strategies are needed. The treatment of colonic cancer remains
      difficult because of the lack of effective chemotherapeutic agents; therefore it
      is important to continue to search for cellular functions that can be disrupted
      by chemotherapeutic drugs resulting in the inhibition of the development and
      progression of cancer. The current knowledge of the modification of proteins by
      myristoylation involving myristoyl-CoA:protein N-myristoyltransferase (NMT) is in
      its infancy. This process is involved in the pathogenesis of cancer. We have
      reported for the first time in rats treated with azoxymethane that NMT activity
      was higher in colonic epithelial neoplasms than in normal colonic tissue and that
      an increase in NMT activity appeared at an early stage in colonic carcinogenesis.
      Increased NMT activity was also confirmed in human colonic tumors compared to
      normal tissue. Furthermore, colorectal tumors displayed increased
      immunohistochemical staining for NMT compared to normal mucosa in the cytoplasm.
      In addition, gallbladder carcinoma showed moderate to strong cytoplasmic
      positivity for NMT with increased intensity in the invasive component whereas the
      normal gallbladder mucosa showed weak to negative cytoplasmic staining for this
      enzyme. It is conceivable therefore that NMT can be used as a potential marker
      for the early detection of cancer. Of particular note is the very recent
      discovery of cytotoxic compounds in the laboratories of the authors which inhibit
      NMT and may offer a novel approach for the evolution of candidate antineoplastic
      agents which display greater potencies towards neoplasms than the corresponding
      normal tissues.

PMID- 12239601
TI  - Keto- and acetyl-keto-boswellic acids inhibit proliferation and induce apoptosis
      in Hep G2 cells via a caspase-8 dependent pathway.
AB  - Boswellic acids are the compounds isolated from the gum resin of Boswellia
      serrata and have been used for the treatment of inflammatory diseases for many
      years in the countries of the east. Recently, a few studies showed that the acids
      may have anti-cancer effect on leukemia and brain tumours. We investigated the
      apoptotic and anti-proliferative effects of two types of boswellic acids, keto
      beta-boswellic acid and acetyl-keto-beta-boswellic acid, on liver cancer Hep G2
      cells. After treating the cells with the boswellic acids, cell proliferation, DNA
      synthesis, and apoptosis were analysed. The activities of caspase-3, -8 and -9
      were assayed. To explore the apoptotic pathway, specific caspase inhibitors were
      employed. It was found that boswellic acids decreased cell viability and
      [3H]thymidine incorporation, checked the cells in the G1 phase, and increased
      percentage of sub-G1. Boswellic acids strongly induced apoptosis accompanied by
      activation of caspase-3, -8 and -9. The apoptosis was blocked completely by
      caspase-8 or caspase-3 inhibitor, but inhibited partly by caspase-9 inhibitor.
      However, these caspase inhibitors did not show any effect on the alternations of
      cell viability caused by boswellic acids. In conclusion, boswellic acids have
      anti-proliferation and anti-cancer effects on Hep G2 cells. The apoptotic effect
      is mediated by a pathway dependent on caspase-8 activation. The acids may be a
      promising drug for the chemoprevention of liver cancer.

PMID- 12239602
TI  - Expression and regulation of WNT10B in human cancer: up-regulation of WNT10B in
      MCF-7 cells by beta-estradiol and down-regulation of WNT10B in NT2 cells by
      retinoic acid.
AB  - WNT signaling molecules, playing key roles in embryogenesis and carcinogenesis,
      are potent targets for regenerative medicine and clinical oncology. We have
      previously cloned and characterized the human orthologue of mouse proto-oncogene
      Wnt-10b using bioinformatics and cDNA-PCR. Human WNT10B is moderately expressed
      in MKN45 and MKN74 cells derived from human gastric cancer, and is up-regulated
      by tumor necrosis factor alpha (TNFalpha) in MKN45 cells. Here, expression and
      regulation of WNT10B in human cancer other than gastric cancer were investigated
      using cDNA-PCR. WNT10B mRNA was expressed in the majority of squamous cell
      carcinoma cell lines derived from esophageal cancer and cervical cancer. WNT10B
      mRNA was relatively highly expressed in TE3, TE6, TE10, TE11 (esophageal cancer),
      Hs700T (pancreatic cancer), SKG-IIIa, HeLa S3 (cervical cancer), and T-47D
      (breast cancer). Expression of WNT10B mRNA was up-regulated by beta-estradiol in
      MCF-7 cells expressing estrogen receptors. Expression of WNT10B mRNA was down
      regulated by all-trans retinoic acid in NT2 cells with the potential of self
      renewal and neuronal differentiation. WNT10B might be implicated in self renewal
      of stem cells as well as in carcinogenesis through activation of the WNT - beta
      catenin pathway.

PMID- 12239603
TI  - An HPLC method for the measurement of 5-fluorouracil in human plasma with a low
      detection limit and a high extraction yield.
AB  - High performance liquid chromatographic (HPLC) techniques for the quantification
      of 5-fluorouracil (5-FU) in human plasma have been reported in the literature,
      however, a low limit of detection was generally found to result in a
      comparatively low extraction yield. We have developed a simple, rapid and
      sensitive HPLC method for the measurement of 5-FU in plasma which provides both a
      low limit of quantification and a high extraction yield. This method involves the
      solid phase extraction of 5-FU from a 500 microl plasma sample. The extract is
      then injected into an HPLC system equipped with a C18 (mu)Bondapak column, and a
      UV detector set at 260 nm. Ethyl acetate and potassium dihydrogen phosphate are
      used for the solid phase extraction and the HPLC mobile phase, respectively. This
      method provides in a good baseline, a sharp and symmetrical peak for 5-FU, and a
      high resolution between 5-FU and the internal standard. The retention time of 5
      FU using this method is 4.7 min with a limit of detection of 5 ng/ml, and an
      extraction yield of 96.2+/-0.5% (SE). The next injection is possible in 11 min,
      and the coefficients of variation are 4.2-8.9% for interday precision, and 5.2
      10.6% for day-to-day reproducibility. An HPLC method has been developed that has
      a low limit of detection and a high extraction yield. This technique was
      successfully applied in a clinical pharmacokinetic study of 5-FU.

PMID- 12239604
TI  - Response of the immune system of mammary tumor-bearing rats to cyclophosphamide
      and soluble low-molecular-mass tumor-associated antigens: the bone marrow and
      thymus.
AB  - We showed in a previous study that soluble low-molecular-mass tumor-associated
      antigens (sTAA) promote the anti-tumor effect of the anticancer drug
      cyclophosphamide (CPA) on rat mammary carcinogenesis. In this report, we analyzed
      the possible mechanism underlying this phenomenon. Studies were performed on the
      bone marrow and thymus from the following groups of rats: i) control rats, ii)
      rats treated with sTAA, iii) rats treated with CPA, iv) rats treated with CPA and
      sTAA. The cellular content of the bone marrow and thymus (CD4+ and CD8+
      lymphocytes) was analyzed morphometrically and immunohistochemically. In the bone
      marrow, CPA caused significant substitution of cellular components with fatty
      tissue whereas sTAA repaired this process. We found that CPA affects mainly the
      process of myelogenesis whereas sTAA protect the production of lymphocytes. In
      the thymus, CPA alone or in combination with sTAA repaired the inhibition effect
      of DMBA on synthesis of CD4+ and CD8+ thymocytes. sTAA further increased the
      amount of CD8+ T lymphocytes in the medulla of the thymus. Data in the literature
      as well as the findings presented here demonstrate that the tested treatment,
      including vaccination with sTAA, actively promotes the generation of the host's
      antitumor immune response.

PMID- 12239605
TI  - Effects of agouti-related protein, orexin and melanin-concentrating hormone on
      oxygen consumption in mice.
AB  - Neuropeptides in the hypothalamus play a pivotal role in the regulation of energy
      balance. Agouti-related protein (AGRP), orexin and melanin-concentrating hormone
      (MCH) have been identified in the hypothalamus as orexigenic peptides. This study
      was undertaken to investigate the effects of AGRP, orexin and MCH on oxygen
      consumption. Oxygen consumption was determined by an O2/CO2 metabolism measuring
      system at 22 degrees C. Mice were kept unrestrained in the chamber without food
      or water during the light cycle, and the oxygen consumption was measured for 2 h
      after intra-cerebroventricular (ICV) administration. ICV administered AGRP (1
      nmol/mouse) significantly decreased oxygen consumption compared to ACSF-treated
      controls. Orexin (1 nmol/mouse) significantly increased oxygen consumption, while
      MCH (1 nmol/mouse) had no significant effect compared to ACSF-treated controls.
      These results suggest that AGRP, orexin and MCH might have different effects on
      energy expenditure, thereby regulating appetite and body weight.

PMID- 12239606
TI  - Dendritic cells pulsed with viral oncolysates potently stimulate autologous T
      cells from cancer patients.
AB  - We demonstrated before that primary operated breast cancer patients contain in
      their bone marrow (BM) cancer reactive memory T cells (MTC) which have to be re
      activated to become tumor infiltrating effector cells. The aim of this study was
      to optimize an ex vivo stimulation protocol for MTC based on autologous dendritic
      cells (DC). As source of tumor antigens we used lysates from unmodified tumor
      cells or from tumor cells infected with Newcastle Disease Virus (NDV) which
      contain IFN-alpha inducing viral dsRNA as one danger signal. DC from breast
      cancer patients were pulsed with lysates from the MCF-7 breast cancer line (Tu-L)
      or from NDV infected MCF-7 cells (TuN-L, viral oncolysates) and compared for
      stimulatory capacity in an ELISPOT response of autologous BM derived MTC. To
      analyze potential further danger signals derived from NDV infection, we employed
      MALDI mass spectrometry, Western blots, FACS cytometry and ELISA tests. DC pulsed
      with viral oncolysates showed increased expression of co-stimulatory molecules in
      comparison to Tu-L pulsed DC and induced significantly higher ELISPOT MTC
      responses. Supernatants from co-cultures of MTC and TuN-L pulsed DC contained
      increased titers of IFN-alpha and IL-15. NDV infection of tumor cells resulted in
      a number of differences in protein expression including a heat-shock protein
      (HSP27) which became phosphorylated. The results suggest that a DC preparation
      pulsed with viral oncolysate includes danger signals (e.g. dsRNA, cytokines, HSP
      molecules) and is superior for MTC stimulation to a DC preparation pulsed with
      lysate from non-infected tumor cells.

PMID- 12239607
TI  - Comprehensive genotypic analysis of human prostate cancer cell lines and sublines
      derived from metastases after orthotopic implantation in nude mice.
AB  - We recently reported on a prostate cancer progression model which was based on
      repeated orthotopic implantation of human prostate cancer cell lines into athymic
      nude mice leading to an increase of tumor cell aggressiveness. To assess
      progression-associated clonal evolution of genotypic changes, we now performed
      comparative cytogenetic characterization of the original cell lines DU145 and PC3
      with derived sublines DU145MN1 and PC3-N. Cell line PC3-125-1L, isolated from a
      lung metastasis after subcutaneous inoculation of PC3 into nude mice, was
      included in the study. Whole-genome analysis was performed using spectral
      karyotyping and comparative genomic hybridization. Fluorescence in situ
      hybridization was used to assess amplification of selected genes, which are
      supposed to play a role in prostate cancer progression. Differences in the
      genetic constitution between parental cell lines and sublines involved gains of
      genetic material at 2q, 5q, 12p/q, and 18p as well as losses at 6p, 7q, 17p, 18q,
      and 22q. Loss of 17p in DU145MN1 and high-level amplification of MYC in PC3-125
      1L resulted in loss of p53 expression and upregulation of Myc expression,
      respectively, as was assessed by Western blotting. Thus, the nude mice model is
      very useful to follow clonal evolution of genetic changes during increase of
      prostate cancer aggressiveness and possibly to clone genes associated with the
      progression of prostate cancer.

PMID- 12239608
TI  - Expression of lymphocyte-specific chemokines in human malignant glioma: Essential
      role of LARC in cellular immunity of malignant glioma.
AB  - Lymphocytes are frequently observed in human malignant glioma, the mechanism(s)
      underlying their appearance is not fully understood. To clarify tumor immunity in
      malignant gliomas, we analyzed the expression of 8 novel lymphocyte-specific
      chemokines in human glioma cell lines and glioma tissues by RT-PCR, Northern
      blot, immunoblot and immunohistochemistry, and examined the correlation with the
      infiltration of various subsets of lymphocytes. For the 8 chemokines examined
      (LARC, TARC, ELC, SLC, PARC, LEC, HCC-2, and SCM-1alpha), expression of LARC was
      clearly detectable in all 12 glioma cell lines by RT-PCR. Additionally,
      expression of TARC and SCM-1alpha was detectable in the majority of glioma cell
      lines. However, the expression level of most chemokines was low, so that Northern
      blot analysis could not demonstrate their expression with the exception of LARC
      in 2 cell lines. Expression of LARC mRNA and LARC protein was strongly induced by
      phorbol myristate ester in U87 MG cells. The production of LARC protein was
      demonstrated in 4 of 8 glioblastoma tissues by immunoblotting, and 9 of 33
      samples (27.3%) by immunohistochemistry. Interestingly, the positivity of LARC
      staining was significantly correlated with the infiltration of CD8-, CD4-, and
      CD45R0-positive cells (p<0.001). Although the constitutive expression level of
      LARC is low, certain stimulations could strongly induce its expression, and play
      a crucial role in the tumor immunity of human malignant glioma.

PMID- 12239609
TI  - The vascular response of tumor and normal tissues in the rat to the vascular
      targeting agent, combretastatin A-4-phosphate, at clinically relevant doses.
AB  - The antivascular actions of disodium combretastatin A-4 3-O-phosphate (CA-4-P)
      were investigated in the rat P22 carcinosarcoma after single doses of 10 or 30 mg
      x kg(-1). Pharmacokinetic data showed that 10 mg x kg(-1) in the rat gave a
      plasma exposure similar to that achieved in the clinic. Blood flow rate to the
      tumor and normal tissues was measured using the uptake of radiolabelled
      iodoantipyrine (IAP). Quantitative autoradiography was used to determine changes
      in spatial distribution of tumor blood flow. Both doses caused an increase in
      mean arterial blood pressure (MABP) and a reduction in heart rate 1 h after
      treatment. Blood flow rate to the tumor decreased to below 15% of control for
      both doses at 1 h, whereas the normal tissues were much less affected. A further
      reduction (to 2% of control at 6 h) was found for 30 mg x kg(-1). Recovery was
      essentially complete by 24 h for both doses. Vascular resistance increased 80
      fold in tumor at 6 h after 30 mg x kg(-1), compared with a maximum 5-fold
      increase in normal tissues. Analysis of the spatial distribution of tumor blood
      flow illustrated an overall reduction in all areas of the tumor at 1 h after 10
      mg x kg(-1), with a tendency for blood flow in the peripheral regions of the
      tumor to recover more quickly than in central regions. Tumor blood flow reduction
      was related to vascular damage including vessel distension, coagulation and
      haemorrhage, and tumor cell damage culminating in necrosis. No pathology was
      evident in any of the normal tissues following treatment. The data provide an
      insight into the mechanisms underlying tissue blood flow changes occurring after
      clinically relevant doses of CA-4-P. It is currently being used to aid
      interpretation of pharmacodynamic data obtained from phase I/II clinical trials
      of CA-4-P and is relevant for future drug development in this area.

PMID- 12239610
TI  - Distinct target regions for chromosome 1p deletions in parathyroid adenomas and
      carcinomas.
AB  - Primary hyperparathyroidism is a common endocrine disease with a multifaceted
      genetic background, the elucidation of which has only begun. Among others, loss
      of the short arm of chromosome 1 and somatic inactivation of the multiple
      endocrine neoplasia type 1 gene (MEN1) in 11q13 represent significant alterations
      in the tumorigenesis. In the present study deletions of 1p were characterized and
      the findings were evaluated in relation to the loci of MEN1 and histone
      deacetylase 1 gene (HDAC1), a menin interacting partner in 1p, as well as to the
      clinical characteristics. Overall 1p LOH was detected in 18 of the 42 tumors
      analyzed (43%), and from the deletion patterns a main target interval of 40 cM
      was identified within 1p band 32.3-36.2. The mapping of HDAC1 centromeric of the
      main interval, and the lack of altered mRNA expression in tumors with LOH,
      suggest that HDAC1 is not the main target for 1p deletions in parathyroid tumors.
      Twenty-five of the 42 tumors (60%) showed alteration of either 1p, of the MEN1
      locus, or both. Tumors with LOH at 11q13 had a significantly higher weight than
      tumors with 1p LOH. In conclusion, LOH in primary sporadic parathyroid adenomas
      occur frequently on the distal part of chromosome 1p and are thus clearly
      different from parathyroid carcinomas where the deletions are more proximally
      located. The findings support that the short arm of chromosome 1 harbors at least
      two different tumor suppressor genes involved in parathyroid tumorigenesis, the
      exact identification of which may provide a molecular basis for differential
      diagnosis of benign and malignant disease in the future.

PMID- 12239611
TI  - p27, cyclin E, and CDK2 expression in normal and cancerous endometrium.
AB  - The objective was to investigate the immunohistochemical expression of p27,
      cyclin E, and CDK2 in normal and cancerous endometrium. Expression of p27 in
      premenopausal normal endometrium was significantly higher than that in
      postmenopausal normal endometrium (p=0.019). A significantly lower amount of p27
      staining was observed in endometrial cancer tissues from premenopausal women than
      in normal premenopausal endometrium (p=0.015). Cyclin E expression in
      premenopausal normal endometrium was significantly higher than that in
      postmenopausal normal endometrium (p=0.003). A significantly higher amount of
      cyclin E staining was observed in endometrial cancer tissues from postmenopausal
      women than in normal postmenopausal endometrium (p=0.017). Regarding menopausal
      status, no significant difference in CDK2 staining was observed between cancerous
      and normal endometrium. There was a positive significant correlation between
      cyclin E and CDK2 expression levels in endometrial cancers (p<0.05). Western blot
      analysis confirmed elevated p27 protein levels in samples with positive p27
      immunostaining. Considerable levels of p27 mRNA were detected in all normal and
      cancerous samples examined by semi-quantitative PCR. No significant relationship
      was found between telomerase activity and its association with p27 and cyclin E
      expression in endometrial cancers. These findings suggested that the decreased
      expression of p27 caused by post-translational mechanism might play an important
      role in endometrial cancer development in premenopausal women. In addition,
      increased cyclin E expression may play an important role in endometrial cancer
      development in postmenopausal women.

PMID- 12239612
TI  - Effects of a high olive oil diet on the clinical behavior and histopathological
      features of rat DMBA-induced mammary tumors compared with a high corn oil diet.
AB  - Effects of a high virgin olive oil diet on the promotion stage of
      dimethylbenz(alpha)anthracene-induced mammary carcinogenesis in rats were
      investigated in comparison with those of a high corn oil diet. Animals were
      randomly placed into 4 groups: control, fed a normolipidic control diet (3% corn
      oil); M, fed a high corn oil diet (20%); O, fed a high olive oil diet (3% corn
      oil plus 17% olive oil); and MO, fed the high olive oil diet after 33 days of
      high corn oil diet. Whereas the high corn oil diet clearly stimulated the mammary
      carcinogenesis, reducing the latency time and increasing the tumor incidence,
      multiplicity and volume, the high olive oil diet led to a lower tumor incidence
      than in the former group, a latency time similar to that of the control and lower
      tumor multiplicity and volume even than in the control group. Moreover, the
      histopathological features of the adenocarcinomas in olive oil groups were
      compatible with a greater degree of differentiation. These data suggest that the
      high virgin olive oil diet would have acted as a negative modulator of the
      experimental mammary carcinogenesis conferring to the tumors a more benign
      clinical behavior and a lower histopathological malignancy in comparison with the
      control and high corn oil diets.

PMID- 12239613
TI  - DNA damage triggers imbalance of proliferation and apoptosis during development
      of preneoplastic foci in the liver of Long-Evans Cinnamon rats.
AB  - The mutant strain Long-Evans Cinnamon (LEC) rat accumulates copper, resulting in
      spontaneous hepatitis and subsequent development of hepatocellular carcinomas
      (HCCs) in the liver, providing a promising model for investigation of the
      relationship between hepatitis induced by oxidative stress and
      hepatocarcinogenesis. We examined DNA strand breaks in peripheral blood cells and
      p53 expression in livers during acute and chronic hepatitis in LEC rats, along
      with preneoplastic lesions, and cell proliferation and apoptosis in non-cancerous
      portions of livers from LEC rats aged 7-115 weeks. Immunohistochemistry using
      antibodies against glutathione S-transferase placental-form (GST-P),
      proliferating cell nuclear antigen (PCNA), and in situ DNA nick labeling (TUNEL)
      were used. Long-Evans Agouti (LEA) rats, a sibling line of the LEC strain, were
      used as controls. In the LEC rats, DNA strand breaks and expression of p53 were
      significantly higher than that of LEA rats at 24 weeks of age. The number of GST
      P-positive (GST-P+) foci/cm2 increased and peaked at 48 weeks old, and the areas
      rapidly expanded thereafter. The level of cell proliferation increased with the
      development of hepatitis and was highest at about 48 weeks old. The induction of
      apoptosis in LEC rats was transiently higher than that in LEA rats during the
      period from 24 to 34 weeks of age. However, the ratio of PCNA-positive cells to
      the apoptotic index showed a growth imbalance in favor of cell proliferation,
      supporting sustained net growth in LEC rats. These findings suggest that DNA
      damage, reflected in DNA strand breaks, plays a critical role in the development
      of hepatocellular preneoplastic foci, with an imbalance between high
      proliferation and relatively low apoptosis.

PMID- 12239614
TI  - Detection of neoplasms in the oral cavity by digitized endoscopic imaging of 5
      aminolevulinic acid-induced protoporphyrin IX fluorescence.
AB  - Studies of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PPIX)
      fluorescence have shown a sensitivity of 95-100% for oral cancer diagnosis, but
      the specificity is only about 50-60%. To improve the diagnostic specificity, a 5
      ALA mediated digitized fluorescence endoscopic imaging system was built in this
      study to enable the on-line image acquisition, analysis and fluorescence
      quantification for the early detection of neoplasms in the oral cavity. PPIX
      fluorescence endoscopy and fluorescence image quantification were performed on 16
      patients with known or suspected premalignant or malignant lesions in the oral
      cavity. Preliminary data from the head and neck clinical trials show that the red
      to-blue intensity ratio of malignant tissue is larger than that of benign tissue.
      By applying the intensity ratio as a diagnostic algorithm, both high specificity
      and sensitivity can be achieved for discriminating malignant tissue from benign
      tissue, and the capability of classifying different histopathological stages of
      oral lesions has also been demonstrated. It was found that the red fluorescence
      intensity distribution in the lesion area could also be obtained to better
      understand the situation of PPIX accumulations in the tissues. Our initial
      results indicate that the digitized endoscopic imaging system combined with the
      fluorescence image quantification method and the ratio diagnostic algorithm
      developed in this study has the potential to significantly improve the non
      invasive diagnosis of early oral neoplasms in vivo.

PMID- 12239615
TI  - CDX2 expression in the stomach with intestinal metaplasia and intestinal-type
      cancer: Prognostic implications.
AB  - CDX2, a transcriptional factor expressed in the intestine, is implicated in the
      development and maintenance of the intestinal mucosa. Recent studies have
      demonstrated that CDX2 is expressed in the intestinal metaplasia of the stomach
      and intestinal-type gastric cancer, while it is not expressed in the normal
      gastric mucosa. To investigate the role of CDX2 in gastric cancer, we determined
      CDX2 expression and cell proliferation rate in various types of gastric cancer
      tissues by immunostaining. Surgically dissected gastric cancer tissues were
      collected from 40 patients. Consistent with previous reports, CDX2 was expressed
      in most gastric mucosa samples with intestinal metaplasia (89%, 16/18), although
      it was not found in the adjacent normal mucosa. CDX2 expression was also detected
      in 64% (18/28) of intestinal-type gastric cancer cases, whereas it was not
      observed in the diffuse-type gastric cancer (0/12). Moreover, the CDX2-positive
      gastric cancer samples showed significantly lower index for Ki-67 immunostaining,
      indicating reduced cell proliferation rates than in the CDX2-negative samples.
      Importantly, multivariate analysis for the overall survival rate revealed that
      the CDX2-positive gastric cancer patients survived significantly longer than the
      CDX2-negative patients. Even among the intestinal-type gastric cancer cases, the
      CDX2-positive group showed a lower Ki-67 index and longer postoperative survival
      than the CDX2-negative group. These results collectively indicate that CDX2
      expression in gastric cancer tissues can be a novel prognostic marker for patient
      survival.

PMID- 12239616
TI  - Establishment of human tumoral ependymal cell lines and coculture with tubular
      like human endothelial cells.
AB  - Ependymomas, rare neoplasms of the central nervous system, occur predominantly in
      children. They are highly vascularized, and histological findings show many
      perivascular rosettes of tumoral cells radially organized around capillaries.
      Treatment of ependymomas relies on surgery combined with radio- or chemotherapy,
      but the efficiency of chemotherapy is limited, probably because of their
      multidrug resistance (MDR) phenotype. Progress in the therapy of these neoplasms
      is dramatically limited by the absence of cell line models. We established
      conditions for the long-term culture of human tumoral ependymocytes and their 3D
      coculture in Matrigel with endothelial cells. Histological, immunological, and
      ultrastructural studies showed that the morphological features (microvilli,
      cilia, and caveolae) of these cultured cells were similar to those of the tumor
      in vivo. The cells expressed potential oncological markers related to the
      immature state of tumoral cells (nestin and Notch-1), their tumorigenicity
      [caveolae and epidermal growth factor-receptor (EGF-R)], or the MDR phenotype [P
      glycoprotein (P-gp)]. The expression of P-gp, EGF-R, and caveolin-1 by these
      tumoral ependymocytes could be useful in studies on new drugs. This coculture
      model might represent a new powerful tool to study new therapeutic delivery
      strategies in tumoral cells.

PMID- 12239617
TI  - Value of expression of p21WAF1/CIP1 as a prognostic factor in advanced middle and
      lower rectal cancer patients treated with preoperative radio-chemotherapy.
AB  - Recent molecular biological studies suggested certain molecular markers might be
      useful as prognostic factors in patients with colorectal cancer. The purpose of
      this study was to investigate whether cyclin dependent inhibitor kinase
      p21WAF1/CIP1 (p21), p53 expression, and/or the presence of apoptosis had
      prognostic value in predicting survival in patients with advanced middle and
      lower rectal cancer who were treated with preoperative radio-chemotherapy. We
      examined the immunohistochemical expression of p21 and p53, and determined the
      degree of apoptosis in resected middle and lower rectal cancers from patients who
      received preoperative radio-chemotherapy (irradiation group, n=40) and from those
      who did not receive treatment (control group, n=35). The preoperative total
      radiotherapy dose was 42.6 Gy and the chemotherapy tegafur suppository dose was
      750 mg/day. Clinicopathological features, and tumor expression of p53 and p21 and
      degree of apoptosis were analyzed by means of multivariate analysis. In the
      irradiation group, tumors were positive for p53, p21 and apoptosis in 34 of 40
      (85.0%), 23 of 40 (57.5%) and 25 of 40 (62.5%) cases, respectively. The
      expression of p21 and the apoptotic index were significantly higher in the
      irradiated group compared to controls (2.0 versus 1.2%, p=0.05; 8 versus 3%,
      p=0.03, respectively). There was a significant correlation between p21
      immunoreactivity and the degree of muscularis propria invasion (p=0.004), as well
      as between p21 immunoreactivity and survival rate (p=0.03). Multivariate analysis
      revealed that p21 expression (RR, 0.09; 95% CI, 0.01-0.78; p=0.03) and lymph node
      metastasis (RR, 3.63; 95% CI, 1.06-12.37; p=0.04) were significant prognostic
      factors for patient survival. These data suggested that p21 expression has
      prognostic value in predicting patient survival in advanced middle and lower
      rectal cancer.

PMID- 12239619
TI  - Maturational sequence of neuroblastoma revealed by molecular analysis on cDNA
      microarrays.
AB  - Neuroblastoma (NB), one of the most common solid tumors among children, is
      histologically classified by the degree of maturation. To elucidate the
      mechanisms underlying its maturational sequence, we analyzed gene-expression
      profiles of 14 NB tumors on cDNA microarrays consisting of 23,040 genes.
      Computational analysis identified 78 genes whose expression levels were
      significantly different between differentiating NB tumors and poorly
      differentiated NB tumors. This group included genes associated with cell
      maturation and apoptosis. Among them we identified 15 that were up-regulated in
      Stage IV NB tumors; these included genes encoding cell adhesion molecules and
      cytoskeleton proteins. The set of genes we report here should contribute to a
      better understanding of NB tumor maturation and could lead to development of new
      therapeutic strategies.

PMID- 12239618
TI  - Rapid lethality of hosts by interleukin-12 following H-2 compatible allogeneic
      bone marrow transplantation: Reminiscence of gut-associated acute graft-versus
      host reaction.
AB  - T lymphocytes and NK cells play an important role in the graft-versus-host (GVH)
      disease. IL-12 is known to activate both lymphocyte subpopulations. Here, we
      examined the effect of IL-12 on the outcome after allogenic bone marrow
      transplantation (allo-BMT). Experiments were performed in a major
      histocompatibility complex (MHC)-matched allo-BMT model from DBA/2 to BALB/c
      mice. We administered IL-12 subcutaneously to recipient BALB/c mice at the day of
      BMT and 2 days later. At a dose of 200 ng IL-12, mice died between day 4 and day
      10. When 50 ng of IL-12 was administered, 50% of the animals died, at a dose of
      25 ng all mice recovered. In vivo blocking experiments with antagonistic
      monoclonal antibodies indicated that the early lethality was mediated by FasL,
      IFNgamma and TNFalpha. Recognition of third party antigens by donor, but not
      recipient lymphocytes caused lethality. HE staining of the large intestine of IL
      12 treated animals showed a severe mucosal injury associated with infiltrating
      lymphocytes and apoptotic bodies. In IL-12 treated mice in contrast to untreated
      control animals, flow cytometry analysis revealed numerous CD3+ T cells and
      CD11c+ dendritic cells (DC) were found in the large intestine. The interaction of
      T cells and antigen presenting DC might contribute to the lethality in our
      system. In light of these findings, the usefulness of IL-12 application for
      patients after BMT is rather questionable.

PMID- 12239620
TI  - Soy isoflavone genistein modulates cell cycle progression and induces apoptosis
      in HER-2/neu oncogene expressing human breast epithelial cells.
AB  - In the multistep progressive pathogenesis of human breast cancer, comedo ductal
      carcinoma in situ (DCIS) represents a preinvasive precursor lesion for therapy
      resistant invasive cancer. Human tissue derived cell culture models exhibiting
      molecular similarities to clinical DCIS facilitate an important preclinical
      mechanistic approach for evaluation of preventive efficacy of natural and
      synthetic chemopreventive compounds. Natural phytochemicals present in fresh
      fruits, vegetables and grain products are likely to offer protection against
      cancer. The clinical efficacy of these natural phytochemicals, however, depends
      on extrapolation, and is therefore equivocal. The present study determined
      whether the natural soy isoflavone genistein (GEN) inhibited aberrant
      proliferation in 184-B5/HER cells (a model for human comedo DCIS) and identified
      possible mechanisms responsible for its efficacy. Human reduction mammoplasty
      derived HER-2/neu oncogene expressing preneoplastic 184-B5/HER cells represented
      the experimental system. Flow cytometry and cellular epifluorescence based assays
      were utilized to quantitate the alterations in cell cycle progression, cellular
      apoptosis, and in the status of cell cycle regulatory and apoptosis-associated
      gene product expression. The 184-B5/HER cells exhibited specific
      immunofluorescence to p185HER, p53, EGFR, but not to ERalpha, thus resembling
      comedo DCIS. Treatment of 184-B5/HER cells with GEN resulted in a dose-dependent
      decrease in the viable cell population, increase in the G0/G1:S + G2/M ratio and
      enhancement of sub G0/G1 (apoptotic population). Exposure to the maximum
      cytostatic 10 microM dose of GEN down-regulated HER-2/neu mediated signal
      transduction as evidenced by a 73.9% decrease (p=0.001) in p185HER specific, and
      a 89.8% decrease (p=0.001) in phosphotyrosine specific immunofluorescence. The
      increase in G0/G1:S + G2/M ratio in response to the treatment with 10 microM GEN
      was associated with a 85.5% decrease (p=0.001) in immunoreactivity to PCNA and a
      128.6% increase (p=0.004) in immunoreactivity to the cyclin dependent kinase
      inhibitor p16INK4. The induction of apoptosis by GEN was associated with a 52.8%
      decrease (p=0.001) in the immunoreactivity to antiapoptotic Bcl-2 and with a
      195.9% (p=0.001) increase in the immunoreactivity to proapoptotic Bax. Thus,
      preventive efficacy of GEN in HER-2/neu+/ER- 184-B5/HER cells may be due to its
      ability to down-regulate HER-2/neu mediated signal transduction, increase the
      expression of the cyclin dependent kinase inhibitor p16INK4, and induce Bcl-2
      dependent apoptosis. These data provide evidence that GEN may be a potential
      chemopreventive lead compound for human comedo DCIS. The 184-B5/HER cells, may
      therefore, provide a high throughput mechanistic bioassay to identify new
      chemopreventive agents for human breast cancer.

PMID- 12239621
TI  - Results of interstitial brachytherapy for malignant brain tumors.
AB  - We evaluated the efficacy of brachytherapy in patients with malignant brain
      tumors and assessed the factors associated with longer disease control after
      treatment. From June 1989 to October 1995, 73 patients were treated with
      stereotactic brachytherapy with temporary placement of iodine-125 implants. The
      median age was 52 (range 9-79). Median KPS was 80. There were 48 patients with a
      glioblastoma multiforme, 13 with an anaplastic astrocytoma, and 12 with other
      tumors. Of the 67 evaluable patients, 20 underwent brachytherapy as part of the
      therapy for a newly diagnosed tumor (17 were glioblastomas) and 46 had
      brachytherapy at the time of progression (28 were glioblastomas). Median survival
      time for all patients undergoing brachytherapy from diagnosis was 70.3 weeks.
      Median survival from implant was 39.3 weeks. For patients with an anaplastic
      astrocytoma, median survival from diagnosis and implant was 158.1 and 36.9 weeks
      respectively. For patients with a glioblastoma multiforme, median survival from
      diagnosis and implant was 62.9 and 37.1 weeks respectively. Eleven patients (16%)
      developed radiation necrosis. Nine patients (13%) developed other complications.
      Age and histologic diagnosis were significant predictors of survival from
      diagnosis. Age and KPS were independent predictors of time to failure after
      implant. Certain characteristics, specifically younger age (<55), and a higher
      KPS (</=70), appear to be associated with longer survival after brachytherapy.
      Complications, some of which are life-threatening, can and do occur.

PMID- 12239622
TI  - Curcumin down-regulates AR gene expression and activation in prostate cancer cell
      lines.
AB  - Curcumin, traditionally used as a seasoning spice in Indian cuisine, has been
      reported to decrease the proliferation potential of prostate cancer cells, by a
      mechanism that is not fully understood. In the current study, we have evaluated
      the effects of curcumin in cell growth, activation of signal transduction, and
      transforming activities of both androgen-dependent and independent cell lines.
      Prostate cancer cell lines, LNCaP and PC-3, were treated with curcumin and its
      effects were further analyzed on signal transduction and expression of androgen
      receptor (AR) and AR-related cofactors using transient transfection assay and
      Western blotting. Our results show that curcumin down-regulates transactivation
      and expression of AR, activator protein-1 (AP-1), nuclear factor-kappaB (NF
      kappaB), and CREB (cAMP response element-binding protein)-binding protein (CBP).
      Curcumin also inhibited the transforming activities of both cell lines as
      evidenced by the reduced colony forming ability in soft agar. The results
      obtained here demonstrate that curcumin has a potential therapeutic effect on
      prostate cancer cells through down-regulation of AR and AR-related cofactors (AP
      1, NF-kappaB and CBP).

PMID- 12239623
TI  - The usefulness of 99mTc-tetrofosmin SPECT scintimammography in the detection of
      small size primary breast carcinomas.
AB  - The aim of this study was to evaluate the usefulness of supine 99mTc-tetrofosmin
      SPECT in the detection of small size breast carcinomas (BC), for which planar
      scintimammography has showed a low sensitivity. We studied 93 patients with
      breast lesions </=10 mm, 69 with BC (14 T1a and 55 T1b, 39 palpable and 30 non
      palpable) and 24 with benign lesions (16 palpable and 8 non-palpable). All
      patients had previously undergone clinical examination and mammography. Ten min
      after 740 MBq 99mTc-tetrofosmin i.v. injection, both planar and SPECT (360
      degrees; angular step: 3 degrees; acquisition time/frame: 30 sec)
      scintimammography were performed in all patients using a rectangular dual head
      gamma camera equipped with HR parallel-hole collimators. In all patients the
      scintigraphic data were related to histology. In the 69 BC patients, SPECT showed
      a significantly higher overall sensitivity than planar (89.8% vs. 46.4%;
      p<0.0005). SPECT gave a higher sensitivity than planar in both T1a (71.4% vs.
      35.7%) and T1b (94.5% vs. 49.1%) carcinomas, and in the latter the difference was
      statistically significant (p<0.0005). SPECT sensitivity was also significantly
      higher in palpable (94.9% vs. 48.7%; p<0.0005) and non-palpable (83.3% vs. 43.3%;
      p<0.005) carcinomas. SPECT and planar imaging showed the same specificity
      (95.8%). SPECT showed a significantly higher overall negative predictive value
      and accuracy than planar (76.7% vs. 38.3% and 91.4% vs. 59.1%, respectively;
      p<0.0005). In our series mammography sensitivity, specificity and accuracy were
      94, 36.8 and 81.4%, respectively. 99mTc-tetrofosmin SPECT is a widely available
      diagnostic method and appears highly accurate in the detection of small size BC,
      improving the low sensitivity of planar scintimammography. In particular, SPECT
      seems indicated for T1b carcinoma detection, although its usefulness in T1a
      carcinomas should not be ignored. A larger clinical application of SPECT as
      complementary tool to mammography is suggested in small size primary BC
      diagnosis.

PMID- 12239624
TI  - Combined use of percutaneous ethanol injection and radiofrequency ablation for
      the effective treatment of hepatocelluar carcinoma.
AB  - Radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) therapy
      are currently used for the treatment of hepatocellular carcinoma (HCC). The
      purpose of this study was to evaluate the usefulness of combination therapy of
      PEI and RFA (PEI-RFA). Seventy-three patients with biopsy-proven HCC and liver
      cirrhosis underwent RFA after a bolus injection of ethanol into HCC. The volume
      of coagulated necrosis in the liver caused by PEI-RFA was estimated and compared
      with that by RFA alone. Coagulated necrosis areas in the liver of patients
      treated with PEI-RFA were significantly larger than those of patients treated
      with RFA alone. In PEI-RFA group, the volume of coagulated necrosis was
      significantly correlated with the amounts of ethanol injected into HCC. No major
      complications were observed during and after the PEI-RFA treatment. These results
      indicate that PEI-RFA is more effective than RFA alone and can make dramatic
      improvement of therapeutic effects in RFA therapy for HCC with fewer sessions of
      treatments. Therefore, PEI-RFA is considered to be a practical and promising
      option and may open up new avenues for the treatment of HCC.

PMID- 12239626
TI  - Induction of cellular senescence in a telomerase negative human immortal
      fibroblast cell line, LCS-AF.1-3, by human chromosome 6.
AB  - In immortal cells (LCS-AF.1-3) which originated from cultured skin fibroblasts
      from a patient with Li-Fraumeni syndrome, a specific deletion has been identified
      on chromosome 6. To examine the relationship between this deletion and the loss
      of function in aging genes, we performed microcell mediated chromosome transfer
      (MMCT) of normal human chromosome 6 into LCS-AF.1-3 cells and analyzed their
      characteristics. Transferred human chromosome 6 induced morphological changes in
      the cells and cellular senescence with growth suppression. In a revertant clone
      that had escaped from induced senescence, a specific deletion was found at D6S309
      in the transferred chromosome 6. High molecular weight telomeric sequences were
      lost in a clone that had been induced to senescence by introduction of human
      chromosome 6. On the other hand, human chromosome 7 induces senescence in
      immortal cells by suppressing the alternative lengthening of telomere (ALT)
      mechanism. We also performed MMCT of chromosome 7 and discuss the effect of
      chromosome transfer by comparing the two chromosomes. LCS-AF.1-3 cells containing
      a transferred chromosome 7 showed no changes in immortality. These results
      suggest that genes which are new candidates for aging and which suppress the ALT
      mechanism are located in the region D6S309 in human chromosome 6.

PMID- 12239625
TI  - Somatic mutation and SNP in the promoter of dbpA and human hepatocarcinogenesis.
AB  - Human DNA-binding protein (dbpA) is a member of a Y-box binding protein family
      containing a cold shock domain. The increased expression of Y box binding
      proteins in somatic cells is associated with cell proliferation and
      transformation. Recently, we isolated a splicing variant of dbpA as a candidate
      for the cellular recombinogenic protein that leads to genomic instability and
      inflammation-mediated hepatocarcinogenesis. The expression of dbpA is enhanced in
      proliferating cells, but the manner in which it regulates transcription is
      largely unknown. In this study, we analyzed the transcriptional regulatory region
      of dbpA, and searched for the mutation in this region by a direct sequence
      method. In 3 of 55 human hepatocellular carcinoma (HCC) cases, we identified one
      nucleotide replacement (T right curved arrow G transversion) in nucleotide
      position -6 of the promoter region. Among 3 cases showing this transversion, one
      HCC case was due to a somatic mutation and the other two were due to single
      nucleotide polymorphism (SNP). By luciferase assay, we showed that the
      transcriptional activity of the promoter region with the transversion was
      significantly higher than that of the wild-type. Using the Southwestern blotting,
      we also confirmed the existence of a cellular proteins (about 25 and 50 kDa) that
      specifically bind to the sequence with this transversion. Our results suggested
      the biological significance of the transversion of dbpA's promoter region as one
      of the factors accelerating hepatocarcinogenesis.

PMID- 12239627
TI  - Apoptosis induced in hepatoblastoma HepG2 cells by the proteasome inhibitor MG132
      is associated with hydrogen peroxide production, expression of Bcl-XS and
      activation of caspase-3.
AB  - This report is focused on the apoptotic effect induced by MG132, an inhibitor of
      26S proteasome, in human hepatoma HepG2 cells. The results were compared with
      those obtained with non-transformed human Chang liver cells. MG132 reduced the
      viability of HepG2 cells in a time- and dose-dependent manner. The effect was in
      tight connection with the induction of apoptosis, as indicated by fluorescence
      microscopy and cytometric analysis, and was accompanied by a remarkable increase
      in the production of H2O2 and a reduction in mitochondrial transmembrane
      potential (Deltapsim). In addition cell death was prevented by antioxidants such
      as GSH, N-acetylcysteine or catalase. Western blot analysis showed that HepG2
      cells contain a very low level of Bcl-2 and a much higher level of Bcl-XL,
      another antiapoptotic factor of the same family. When the cells were exposed to
      MG132 the level of Bcl-XL diminished, while a new band, corresponding to the
      expression of the proapoptotic protein Bcl-XS was detected. MG132 also caused the
      release of cytochrome c from mitochondria and the activation of caspase-3 with
      the consequent degradation of poly-ADP ribose polymerase (PARP). The observation
      that the broad spectrum caspase inhibitor z-VAD markedly reduced the apoptotic
      effect of the drug clearly demonstrated that caspases play an important role in
      MG132-induced apoptosis. MG132 exerted a modest effect on the viability of Chang
      liver cells which primarily depended on the G2/M arrest of cell cycle while only
      a small percentage of apoptotic cells was found. The remarkable differences in
      the effects induced by MG132 in Chang liver cells and HepG2 cells made us
      hypothesise the potential use of proteasome inhibitors in hepatocarcinoma
      therapy.

PMID- 12239628
TI  - The IL-6 receptor super-antagonist Sant7 enhances antiproliferative and apoptotic
      effects induced by dexamethasone and zoledronic acid on multiple myeloma cells.
AB  - Interleukin-6 (IL-6) is the major growth and survival factor for multiple myeloma
      (MM), and has been shown to protect MM cells from apoptosis induced by a variety
      of agents. IL-6 receptor antagonists, which prevent the assembly of functional IL
      6 receptor complexes, inhibit cell proliferation and induce apoptosis in MM
      cells. We have investigated whether the IL-6 receptor super-antagonist Sant7
      might enhance the antiproliferative and apoptotic effects induced by the
      combination of dexamethasone (Dex) and zoledronic acid (Zln) on human MM cell
      lines and primary cells from MM patients. Here we show that each of these
      compounds individually induced detectable antiproliferative effects on MM cells.
      Sant7 significantly enhanced growth inhibition and apoptosis induced by Dex and
      Zln on both MM cell lines and primary MM cells. These results indicate that
      overcoming IL-6 mediated cell resistance by Sant7 potentiates the effect of
      glucocorticoides and bisphosphonates on MM cell growth and survival, providing a
      rationale for therapies including IL-6 antagonists in MM.

PMID- 12239629
TI  - IVIg to prevent tumor metastases (Review).
AB  - Intravenous gamma globulin (IVIg) is produced from a pool of precipitated IgG
      from over 3,000 healthy donors. IVIg was originally given to subjects with Igs
      deficiencies. Later on its beneficial effects on a diverse autoimmune clinical
      conditions were revealed. Based on large experimental studies in mice as well as
      limited clinical experience, we consider IVIg useful in preventing metastatic
      spread. In mice, the employment of IVIg reduced significantly metastatic spread
      of melanoma, carcinoma and sarcoma. The effect of IVIg was achieved following
      i.v. or s.c. administration at high dose (2 g/kg body weight) and at 100 times
      lower doses. The effect of IVIg on the prevention of metastases are diverse and
      achieved via enhancement of IL-12 secretion and increased NK activity as well as
      inhibition of matrix metalloproteinase-9 (MMP-9). The lack of serious side
      effects with the remarkable decrease in metastatic spread make IVIg a suitable
      adjuvant therapy in early and advanced cancer conditions.

PMID- 12239630
TI  - Cytokine regulation of constitutive production of interleukin-8 and -6 by human
      pancreatic cancer cell lines and serum cytokine concentrations in patients with
      pancreatic cancer.
AB  - Patients with pancreatic cancer frequently demonstrate symptoms such as weight
      loss and muscle wasting and have clinical evidence of a systemic inflammatory
      response. Such effects may be mediated by pro-inflammatory cytokines derived from
      tumor cells. The production of interleukin-6 and -8 by pancreatic cancer cell
      lines and the influence of other cytokines on this production was studied. IL-8
      was produced by all cell lines and production was increased following exposure to
      IL-1 and TNF. Cytokine-stimulated, but not basal IL-8 production was reduced by
      co-incubation with IL-4 in the MIA PaCa-2 and PANC-1 cell lines. The CFPAC cell
      line produced IL-6, but this production was not altered by IL-1, TNF or IL-4. In
      the PANC-1 cell line IL-8 and IL-8 receptors were only detected by PCR in cells
      which had been stimulated with TNF or IL-1. Serum concentrations of IL-6 and IL-8
      were elevated in patients with pancreatic cancer compared with controls. In
      conclusion, human pancreatic cancer cell lines elaborate pro-inflammatory
      cytokines which have the potential to mediate elements of the systemic
      inflammatory response.

PMID- 12239631
TI  - Genomic imbalances in T-cell acute lymphoblastic leukemia cell lines.
AB  - Genomic imbalances were investigated in 15 T-cell acute lymphoblastic leukemia
      cell lines using the comparative genomic hybridization (CGH) technique. In
      addition, in vitro response to the cytostatic drug doxorubicin was evaluated by
      means of a growth inhibition assay. The number of significant DNA copy number
      alterations (CNAs) varied from 0 to 16 per cell line and the number of additional
      alterations with borderline significance was in a range of 0-7. Three of the cell
      lines had a total number of genomic changes of >/=20, five had 11-19, and eight
      had </=10 CNAs. One cell line did not show any imbalance at all. Among the
      significant CNAs, losses of genomic material were slightly more frequent than
      gains (60:49). Gains dominated among the borderline alterations compared to
      losses (45:9). CNAs common to all cell lines examined were not found. The most
      frequent genomic imbalance (gain of 6q23) was shared by 9 of the 15 cell lines. A
      significant loss of 18q23 was observed in eight lines, however, often close to
      borderline significance. Seven of the cell lines were characterized by a loss of
      the entire short arm of chromosome 9 or parts of it with 9p21 as minimal band of
      overlap. Interestingly, cell lines with a 9p21 deletion exhibited twice the
      number of gains and 1.6 times the number of losses per line as compared with the
      cell lines without this deletion. A consistent pattern of the CNAs accompanying
      the 9p deletion could not be detected, although some associations were more
      obvious than others, e.g., gains of 6q22 in five cell lines with del(9p21), of
      6p21 in four lines combined with a gain of 6q22, and of 20q in four cell lines,
      of 1p32 in three of these seven lines, a loss of 14q32 in three of them. Three of
      the lines with 9p deletion had gains of 6p21, 6q22 and 20q in common. Enh(6q22)
      or dim(14q32), respectively, were found in only one of the nine cell lines
      without the 9p deletion. Based on the dose response curves of the cell lines for
      doxorubicin, eight doxorubicin-sensitive cell lines had an inhibition
      concentration 50% (IC50) <10 nM (CCRF-CEM2, JURKAT, KE-37, MOLT-3, MOLT-4, P12
      Ichikawa, PEER, and RPMI-8402) and seven doxorubicin-resistant cell lines had an
      IC50 >10 nM (BE-13, CCRF-CEM1, HUT-78, J-Jhan, Karpas-45, MOLT-17, and PF-382).
      The average number of CNAs per cell line was higher in the sensitive than in the
      resistant group (total 13.1:8.5; significant CNAs 9.1:5.8).

PMID- 12239632
TI  - Expression of WNT7A in human normal tissues and cancer, and regulation of WNT7A
      and WNT7B in human cancer.
AB  - WNT signals are transduced through seven-transmembrane-type WNT receptors encoded
      by Frizzled (FZD) genes to the beta-catenin - TCF pathway, the JNK pathway or the
      Ca2+-releasing pathway. WNT signaling molecules are potent targets for diagnosis
      of cancer (susceptibility, metastasis, and prognosis), for prevention and
      treatment of cancer, and for regenerative medicine or tissue engineering. We have
      so far cloned and characterized human WNT signaling molecules WNT2B/WNT13, WNT3,
      WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT10A, WNT10B, WNT11, WNT14,
      WNT14B/WNT15, FZD1, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD10, FRAT1,
      FRAT2, NKD1, NKD2, VANGL1/STB2, ARHU/WRCH1, ARHV/WRCH2, GIPC2, GIPC3,
      betaTRCP2/FBXW1B, SOX17, and TCF-3 using bioinformatics, cDNA-library screening,
      and cDNA-PCR. Here, expression of WNT7A in human normal tissues and cancer, and
      regulation of WNT7A and WNT7B in human cancer were investigated. WNT7A was highly
      expressed in fetal lung, adult testis, lymph node, and peripheral blood
      leukocytes. WNT7A was relatively highly expressed in temporal lobe, occipital
      lobe, parietal lobe, paracentral gyrus of cerebral cortex, caudate nucleus,
      hippocampus, medulla oblongata and putamen within adult brain. WNT7A was highly
      expressed in SW480 (colorectal cancer), BxPC-3 and Hs766T (pancreatic cancer),
      and was also expressed in MKN7 and MKN45 (gastric cancer). WNT7B rather than
      WNT7A was expressed in MCF-7 (breast cancer) and NT2 (embryonal tumor). beta
      estradiol did not affect expression levels of WNT7A and WNT7B in MCF-7 cells.
      WNT7B, but not WNT7A, was slightly up-regulated by all-trans retinoic acid in NT2
      cells.

PMID- 12239633
TI  - Hepatic intra-arterial injection of 1,25-dihydroxyvitamin D3 in lipiodol: Pilot
      study in patients with hepatocellular carcinoma.
AB  - 1,25-dihydroxycholecalciferol [1,25-(OH)2 D3] has been shown to have
      antiproliferative effects in a wide variety of cancer cell lines. In vivo
      studies, although often limited by the development of hypercalcemia, have also
      shown the potential usefulness of 1,25-(OH)2 D3 in inhibiting tumor growth. The
      potential usefulness of the drug has been hampered by the development of
      hypercalcemia. This pilot clinical study was designed to evaluate the preclinical
      results that have shown, locoregional administration of 1,25-(OH)2 D3 in lipiodol
      can prevent the development of hypercalcemia. Eight patients with refractory HCC
      were given a single intrahepatic arterial dose (50, 75 or 100 microg) of 1,25
      (OH)2 D3 dissolved in 5 ml of lipiodol. Following this, for 4 weeks serum
      calcium, 1,25-(OH)2 D3, alpha-fetoprotein and a range of biochemical indices were
      monitored. While, in 3 patients the calcium levels exceeded the normal range,
      even at these extremely high doses, non of the patients developed grade 3
      hypercalcemia. 1,25-(OH)2 D3 administration also led to transient stabilization
      of serum alpha-fetoprotein in these patients. The data obtained support the
      hypothesis that, in patients with HCC, locoregional delivery of 1,25-(OH)2 D3 in
      lipiodol can allow administration of supra-pharmacological doses of the drug
      without the development of hypercalcemia.

PMID- 12239634
TI  - Transcription and expression of CD44 variant exons by oro-pharyngeal squamous
      cell carcinomas.
AB  - The CD44 cell surface hyaluronan binding protein has many isoforms formed by
      alternative splicing and glycosylation, and some variants have been associated
      with a malignant phenotype, invasion and metastasis. CD44 splicing patterns and
      intron 9 retention in 24 oro-pharyngeal squamous cell carcinomas (OSCC) were
      investigated by RT-PCR. Transcription efficiency and quantity were determined in
      10 carcinomas and normal control mucosa by real-time PCR using dual-labeled
      fluorescent Taqman probes. Most of the carcinomas, regardless of grade, showed
      one major transcript including exons v2-v10, similar to that expressed by normal
      keratinocytes. In addition, most carcinomas expressed a variety of truncated
      transcripts of contiguous variant exons. Real-time PCR revealed that carcinomas
      showed both over-expression and down-regulation in transcription compared to
      normal keratinocytes, but this change was independent of the state of
      differentiation or the sub-site of biopsy. Intron 9 was not retained in normal
      keratinocytes or carcinomas. Overall, the results indicate that OSCC, like normal
      keratinocytes, constitutively express all variant exons and that the missplicing
      seen in other malignancies does not appear to occur. OSCC do not reproducibly
      over-express CD44 and show a wide range of transcription levels. CD44 expression
      does not appear to be fundamentally deranged in OSCC and is unlikely to be of
      value in early diagnosis, or as a prognostic marker.

PMID- 12239635
TI  - The peroxisome proliferator-activated receptor gamma ligand 15-deoxy-Delta12,14
      prostaglandin J2 induces vascular endothelial growth factor in the hormone
      independent prostate cancer cell line PC 3 and the urinary bladder carcinoma cell
      line 5637.
AB  - Cyclopentenone-prostaglandin derivatives, including the peroxisome-proliferator
      activated receptor gamma (PPARgamma) ligand 15-deoxy-Delta12,14-prostaglandin J2
      (15d-PGJ2), inhibit tumor cell growth in vitro and in vivo. As 15d-PGJ2 was found
      to stimulate the expression of vascular endothelial growth factor (VEGF) in
      endothelial cells, we investigated whether 15d-PGJ2 induces this angiogenic
      factor in the human androgen-independent PC 3 prostate and the 5637 urinary
      bladder carcinoma cell line. In PC 3 cells, 15d-PGJ2 caused a dose-dependent
      increase in VEGF mRNA expression, as determined by RT-PCR. Stimulation started
      after 6 h, and after 72 h, VEGF mRNA expression reached a maximum of 3.3+/-0.3 U,
      4.4+/-0.3 U and 6.1+/-0.1 U with 1, 5 and 10 microM 15d-PGJ2, respectively.
      Between 12-72 h, VEGF protein production was stimulated by up to 2-fold with 5
      and 10 microM 15d-PGJ2 as assessed by ELISA in PC 3 cell-conditioned medium. In
      5637 cells, 15d-PGJ2 did not alter VEGF mRNA expression for up to 72 h.
      Thereafter, VEGF mRNA expression was transiently increased from 2.3+/-0.8 U in
      control cells to 4.6+/-0.5 U in 1 microM and 5.9+/-0.6 U in 5 microM 15d-PGJ2
      treated cells. VEGF protein production was only moderately stimulated (1.7-fold).
      10 microM 15d-PGJ2 had no effect on VEGF mRNA expression in 5637 cells, but
      effectively reduced viability in both cell lines. 15d-PGJ2 also increased
      PPARgamma mRNA expression in both cell lines. While in PC 3 cells, stimulation of
      PPARgamma mRNA expression occurred after 72 h, in 5637 cells, a transient
      stimulation took place after 6 h (4-fold). We demonstrated that 15d-PGJ2 induces
      VEGF in PC 3 and 5637 cancer cells. This might be important if PG-analogues are
      considered as antitumor agents.

PMID- 12239636
TI  - Cloning and characterization of SLP3: a novel member of the stomatin family
      expressed by olfactory receptor neurons.
AB  - The detection of odorants with high sensitivity and specificity utilizes
      specialized transduction proteins that may be assembled into complexes to afford
      enhanced speed and efficiency in olfactory neurons. We have used a differential
      cDNA screening technique to identify novel gene products that display restricted
      expression within the olfactory epithelium. Here we report the characterization
      of an olfactory neuronal protein, SLP3, which shares extensive homology with the
      stomatin family of membrane proteins. Other stomatin family members have been
      implicated in specific interactions with ion channels and G protein-coupled
      receptors. The pattern of SLP3 mRNA expression during embryonic development and
      the subcellular localization of the SLP3 protein in mature olfactory neurons
      observed here is consistent with a specific role for this protein in the
      assembly, translocation, or function of the odorant transduction complex in
      olfactory neurons.

PMID- 12239638
TI  - Testicular microlithiasis: histologic and immunohistochemical findings in 11
      pediatric cases.
AB  - Testicular microlithiasis (TM) is being recognized with increasing frequency
      because of the extensive use of ultrasound. TM has been linked to several
      pathological conditions of the testis, mainly with an increased risk for
      developing germ cell tumors. The pathogenesis of the microcalcospherites is
      unknown. We report a detailed morphologic and immunohistochemical analysis of 11
      patients (age: 3 to 15 years) with TM. The microliths were related neither to the
      age of the children nor to the developmental stage of the testis. The
      microcalcospherites were PAS positive or collagen IV positive or surrounded by a
      collagen IV-positive band, extratubular structures consistently associated with
      double-layered annular tubules. Immature, smaller Sertoli cells commonly lined
      the inner layer of the annular tubules. Some microcalcospherites showed an
      interposed thin band of connective tissue cells between the concretion and the
      tubular basement membrane. The annular tubules seemed to result from progressive
      wrapping of the growing tubules around the concretions. Our findings favor the
      interpretation that the microliths are located outside the tubules and have been
      present there since very early stages of testicular development. The association
      of the calcospherites with Sertoli cells and annular tubules formation, like that
      of gonadal stromal tumor with annular tubules of the ovary and large cell
      calcifying Sertoli cell tumor of the testis, favors the hypothesis that
      microliths may result from multifocal Sertoli cell dysfunction. Since both tumors
      are related to the Peutz-Jeghers syndrome, it is proposed that TM may result from
      the same genetic abnormalities. It is unclear how this may be related to the
      development of germ cell tumors. However, the presence of calcospherites in
      gonadoblastoma may indicate a combined Sertoli cell and germ cell derangement in
      the genesis of TM.

PMID- 12239639
TI  - Isolated iliac artery aneurysmocolonic fistula with pericolic abscess.
AB  - We report the successful management of a 66-year-old man who had common iliac
      aneurysmosigmoid colon fistula. The initial presentation was abdominal pain,
      fever, and melena. Digital subtraction angiography showed no evidence of rupture.
      However, computed tomography scanning revealed fine gas formations in the common
      iliac artery aneurysm. To reduce the risk of graft infection and prolonged
      ischemia, we created an extraabdominal femoral-femoral bypass graft, closed the
      wounds, removed the aneurysm, and closed the colon primarily. The postoperative
      course and recovery were uneventful.

PMID- 12239640
TI  - Operative intervention for recurrent stenosis after carotid stent angioplasty: a
      report.
AB  - Carotid artery angioplasty and stenting is gaining popularity, yet the natural
      history and optimal treatment for recurrent stenoses within stents are not known.
      Recurrent stenosis rates are not well characterized, with rates between 0 and 33%
      reported within the first year. Treatment of these lesions with repeat
      angioplasty may not be feasible or desirable, leading to operative interventions.
      We present two cases of asymptomatic high-grade in-stent restenosis treated
      successfully with carotid artery bypass using PTFE.

PMID- 12239641
TI  - Carotid artery reconstruction combined with myocutaneous flap coverage: a complex
      and durable rescue operation.
AB  - Carotid reconstruction combined with myocutaneous flap coverage is a rare and
      challenging operation. We reviewed our experience to define the indications and
      outcome of this complex procedure. Clinical data and neurologic, wound, and
      vascular complications of all patients who underwent carotid artery
      reconstruction combined with myocutaneous flap coverage over a 17-year period
      were retrospectively reviewed. Results from this procedure indicate that
      pectoralis major myocutaneous flap is a safe and durable option for wound
      coverage in patients who undergo carotid endarterectomy, resection, and/or
      reconstruction for neck malignancy, previous irradiation or graft infection. Late
      outcome is favorable with low neurologic, vascular, and wound complication rates.

PMID- 12239643
TI  - Outcome analysis of laparoscopic Roux-en-Y gastric bypass for morbid obesity. The
      first 116 cases.
AB  - BACKGROUND: Morbid obesity has been described as a continuing epidemic affecting
      a growing portion of our population. We report an outcome analysis of our early
      experience with laparoscopic Roux-en-Y gastric bypass (LRYGB) in the treatment of
      morbid obesity. METHODS: Two surgeons performed 116 consecutive LRYGBs at a
      single institution, creating a 25-ml pouch and a 90- to 150-cm Roux limb. The
      prospectively collected data included patient demographics, comorbidities,
      postoperative weight loss, and complications. RESULTS: All eight conversions to
      an open procedure occurred early during the experience of the surgeons. The mean
      operating room time for the first 50 cases was 272 min, which decreased to 198
      min with experience. The mean length of hospital stay was 3 days. There were 34
      complications in 27 patients (23.3%), 14 of which (12%) required reoperation. At
      18 months postoperatively, the patients had lost 77% of their excess weight, and
      their body mass index had decreased from a mean of 49.3 to 32.6 kg/m2. As a
      result of LRYGB, 25% of the patients were rendered completely free of any
      pharmacologic treatment for their preexisting comorbidities. CONCLUSIONS:
      Although technically challenging, LRYGB can be performed safely with excellent
      long-term results. The mean operating room time and conversion rate improved with
      experience. As this study showed, LRYGB achieves an excellent rate of weight loss
      and improvement in preoperative comorbidities with a minimal length of hospital
      stay and an acceptable complication rate.

PMID- 12239642
TI  - A comparison of antegrade and retrograde mesenteric bypass.
AB  - Mesenteric artery bypass originating from the supraceliac aorta (antegrade
      bypass) has been the standard orientation of visceral artery bypass grafts.
      Retrograde bypass, in which the bypass originates from the iliac arteries, has
      not been as widely accepted. The purpose of our study was to compare the results
      of these two types of bypass in a similar population. We retrospectively reviewed
      the records of patients undergoing mesenteric artery bypass at two tertiary care
      medical centers (UCLA Medical Center, Beth Israel Deaconess Medical Center).
      Between February 1992 and January 2001, 37 patients underwent 39 mesenteric
      bypass procedures. The choice of bypass orientation (antegrade versus retrograde)
      was determined by the individual surgeon. Chart review, duplex ultrasonography,
      and/or telephone interviews were used to assess symptom-free survival. Actuarial
      analysis was completed using Kaplan-Meier survival estimates. From this
      assessment we were able to determine that symptom-free survival of patients
      undergoing retrograde mesenteric bypass is similar to that seen in antegrade
      bypass. Primary retrograde bypass is a valid option for patients undergoing
      mesenteric bypass.

PMID- 12239644
TI  - Role of appendectomy in training for laparoscopic surgery.
AB  - BACKGROUND: This study aimed to evaluate a program of training in laparoscopic
      surgery based on clinical practice in the emergency room, in which laparoscopic
      appendectomy is the first technique that residents perform as surgeons. METHODS:
      A prospective nonrandomized study was conducted involving all the laparoscopies
      performed in emergencies with a diagnosis of acute abdomen, appendicular in
      origin, during the period between June 1991 and December 1997. RESULTS: There
      were no statistically significant differences between residents and assistants in
      terms of conversion rates (22/242 vs 15/158), mean hospital stay for each type of
      surgeon (5.2 days for residents and 5.1 days for assistants), and complications
      (12.8% for residents and 13.7% for assistants). Operating time, was significantly
      longer (p < 0.05) for residents (52.2 min) than for assistants (48 min).
      CONCLUSIONS: Apprenticeship in laparoscopic appendectomy can be accomplished with
      gradual clinical training and without the need for resort to animal
      experimentation laboratories.

PMID- 12239645
TI  - Laparoscopic hepatectomy and dissection of lymph nodes for intrahepatic
      cholangiocarcinoma. Case report.
AB  - Usually intrahepatic cholangiocarcinoma has a poor prognosis, especially when it
      occurs with lymph node metastasis. As a treatment for intrahepatic
      cholangiocarcinoma, dissection of lymph nodes alone does not seem to offer any
      significant advantages. The laparoscopic hepatectomy procedure, however, is a
      minimally invasive liver surgery. We recently had the case of a patient who
      underwent successful laparoscopic hepatectomy and dissection of lymph nodes for
      intrahepatic cholangiocarcinoma in the left lateral segment of the liver. The
      patient had intrahepatic cholangiocarcinoma with distant lymph node metastasis
      around the common hepatic artery determined to stage IVb according to TNM
      classification. The operation time was 335 min, and the total blood loss was only
      225 ml. A left lateral hepatectomy and complete lymph node dissection around the
      hepatoduodenal ligament and celiac trunk was performed. In this case, a
      laparoscopic procedure enabled the patient to have an early discharge, and there
      was no recurrence for 14 months. Another advantage for this patient was that the
      hospital stay lasted only 10 days. As compared with conventional surgery,
      laparoscopic surgery reduces blood loss and shortens the hospital stay. In
      conclusion, laparoscopic surgery for intrahepatic cholangiocarcinoma is a good
      treatment for advanced intrahepatic cholangiocarcinoma because it allows a
      positive early postoperative outcome and possibly a better result over the long
      term.

PMID- 12239646
TI  - Computer-enhanced robotic telesurgery. Initial experience in foregut surgery.
AB  - BACKGROUND: A new type of computer-enhanced telemanipulator device for "robotic"
      laparoscopic surgery was recently approved. We prospectively evaluated the
      initial patients undergoing procedures with this new device at our institution.
      METHODS: Patient demographics, operative indications, port placement, operative
      time, robot time, complications, and hospital stay were recorded. Follow-up
      evaluation was appropriate for the individual procedure. RESULTS: Initially, 35
      cases were managed. There were 22 anti-reflux procedures, 9 Heller myotomies, 1
      pyloroplasty, 1 distal pancreatectomy with splenectomy, 1 esophagectomy with
      intrathoracic anastomosis, and 1 diagnostic laparoscopy. The operative times
      ranged from 88 to 458 min. The robot use times were between 16 and 185 min. There
      were no device-related complications. CONCLUSIONS: Computer-enhanced robotic
      telesurgery is a safe and effective treatment method for a variety of diseases of
      the proximal gastrointestinal tract. Further study is needed to determine the
      benefits of this approach as compared with current technology.

PMID- 12239647
TI  - Laparoscopic harvesting of small bowel graft for small bowel transplantation.
AB  - BACKGROUND: Small bowel transplantation represents a valid therapeutic option for
      patients with intestinal failure, obviating the need for long-term total
      parenteral nutrition. Recently, reports have shown the feasibility of performing
      living related intestinal transplantation using segmental small bowel grafts. The
      limitations of this technique include inadequate harvested small bowel lengths,
      as compared with the lengths obtained in cadaveric small bowel harvests, and
      large incisions for the donor. In this pilot study, we evaluated the feasibility
      of laparoscopically harvesting long segments of proximal jejunum for small bowel
      transplantation using a porcine model. The results can be used to evaluate the
      potential for applying this technique in human cases. METHODS: For this study 10
      yorkshire pigs were used. Under general anesthesia, each pig underwent
      laparoscopic segmental resection of 200 cm of proximal jejunum on a vascular
      pedicle. The harvested graft then was autoreimplanted using an open technique by
      anastomosing the vascular pedicle to the superior mesenteric vessels. Success was
      determined 2 hours after anastomosis by visually identifying a pink graft with
      viable-appearing mucosa, an artery with a strong thrill, and palpable venous
      flow. The animals were then sacrificed. RESULTS: The mean operation time required
      to laparoscopically harvest the small bowel graft was 80 min (range, 35-120 min),
      and the mean length of harvested graft was 220 cm (range, 200-260 cm). The mean
      length of the graft's vascular pedicle was 4.5 cm (range, 4-5 cm). All 10 grafts
      were successfully harvested laparoscopically and then reimplanted using an open
      technique. All the grafts maintained good vascular flow, and showed no evidence
      of mucosal necrosis at necropsy. Obviously, further studies would be required to
      examine the long-term results of reimplanting a laparoscopically harvested small
      bowel graft, but proposals for such studies is beyond the scope of this report.
      CONCLUSION: Minimally invasive techniques can be used to harvest proximal small
      bowel grafts for living related small bowel transplantation.

PMID- 12239648
TI  - Small bowel obstruction after laparoscopic donor nephrectomy.
AB  - BACKGROUND: Laparoscopic live donor nephrectomy has become the procedure of
      choice for kidney procurement at many centers worldwide. A decrease in
      postoperative pain and length of stay, a faster return to work, and no difference
      in morbidity and mortality compared to open nephrectomy have all been reported.
      However, few data exist regarding the complication of postoperative internal
      hernia and small bowel obstruction, which is unique to a
      laparoscopic/transperitoneal approach. METHODS: We present three case reports of
      patients who developed small bowel obstruction from an internal hernia and
      mesenteric defect after laparoscopic donor nephrectomy. RESULTS: A total of 635
      patients underwent laparoscopic donor nephrectomy between March 1996 and August
      2001 at our institution. Small bowel obstruction developed in three patients
      (0.47%) within 1 week postoperatively. Each case involved an internal hernia
      through a left colon mesenteric defect at the site of nephrectomy. Reoperation
      was necessary in each case and was associated with a prolonged hospital stay
      (mean, 22.3 days; range, 6-37). Two patients were managed with laparotomy; one
      patient underwent a laparoscopically assisted exploration. One patient required
      an additional open exploration for intraabdominal sepsis and cholecystectomy.
      CONCLUSIONS: Small bowel obstruction from internal hernia following laparoscopic
      donor nephrectomy is a rare event, but it can lead to significant morbidity in an
      otherwise healthy patient. These patients may be at higher risk for bowel
      obstruction given the soft tissue defect remaining after nephrectomy. Vigilance
      is required when mobilizing the colon to ensure that mesenteric defects are
      recognized and repaired.

PMID- 12239649
TI  - The importance of understanding the basics of imaging in the era of high-tech
      endoscopy: part II. Logic, reality, and Utopia.

PMID- 12239650
TI  - Does major depression in patients with gastroesophageal reflux disease affect the
      outcome of laparoscopic antireflux surgery?
AB  - BACKGROUND: It is known that psychological factors can affect end points of
      surgical treatment. The current study aimed to evaluate the outcome of
      laparoscopic antireflux surgery (LARS) in patients with gastroesophageal reflux
      disease (GERD) who experience concomitant major depression in comparison with
      GERD patients who have no known comorbidity. METHODS: Among a sample of more than
      550 patients who underwent LARS, a group of 38 GERD patients with concomitant
      major depression (MD) were included in this study. The patients included 24 women
      and 14 men, with a mean age of 51 years. A group of 38 control patients (non-MD)
      matched in terms of age, gender, and esophageal manometry findings was selected
      from the database for comparison of surgical outcomes between patients with GERD
      accompanied by concomitant major depression and GERD patients with no known
      comorbidity. In each group, 23 patients received a Toupet fundoplication and 15
      patients underwent a "floppy" Nissen fundoplication. The following factors were
      evaluated before surgery, 3 months afterward, and 1 year after LARS: symptoms
      (heartburn, regurgitation, chest pain, bloating, and dysphagia), quality of life
      (Gastrointestinal Quality of Life Index [GIQLI]), lower esophageal sphincter
      pressure (LESP), and 24-h pH monitoring (DeMeester score). RESULTS: Before and
      after surgery, there were no significant differences between the two groups in
      terms of LESP and DeMeester score. Preoperative GIQLI showed significant
      differences (p < 0.05) between the two groups (MD group, 71.8 +/- 8.6 vs non-MD
      group, 91.1 +/- 9.8), and significant differences (p < 0.01-0.001) between the
      mean data and that for healthy individuals (122.6 +/- 8.5). The GIQLI scores had
      improved significantly at 3 months and at 1 year after surgery (p < 0.05-0.001)
      in all the patients (1 year postoperatively: MD group, 99.3 +/- 8.6 vs non-MD
      group, 121.9 +/- 9.7). Before surgery, when symptoms were compared between the
      two groups, significant differences (p < 0.001) were found in the percentage of
      chest pain (81.6% vs 37.4%) and bloating (92.2% vs 37.4%), showing that these
      symptoms were more predominant and graded as much more severe among patients with
      MD. In both groups, all the symptoms but dysphagia showed a significant
      improvement in severity (p < 0.05-0.0001). A comparison of both groups
      postoperatively showed that significant differences were still present in chest
      pain (44.7% vs 2.6%), bloating (68.4% vs 18.4), and dysphagia (50.1% vs 2.6%). A
      significant difference (p < 0.001) was observed only in patients with major
      depression and depending on the kind of wrap procedure (Nissen vs Toupet),
      showing that dysphagia (78.9% vs 21.1%) and chest pain (82.4% vs 17.6%) were much
      more predominant in patients who underwent "floppy" Nissen fundoplication.
      CONCLUSIONS: Even if they are good surgical candidates from a physiologic point
      of view, GERD patients with concomitant major depression should be selected
      carefully. In these patients, LARS can normalize physiologic data, but some
      patients have demonstrated less symptomatic relief, suffered from postoperative
      dysphagia, and showed less quality-of-life improvement. Eventually, laparoscopic
      Toupet fundoplication used with these patients could result in a better
      subjective outcome.

PMID- 12239651
TI  - Hand-assisted laparoscopic colon mobilization for esophageal reconstruction.
AB  - BACKGROUND: New techniques for hand-assisted laparoscopic colon surgery have been
      adopted quickly for the treatment of numerous colorectal diseases. However,
      reports of laparoscopic colonic mobilization for esophageal reconstruction are
      rare. In this report we describe an improved procedure for esophageal
      reconstruction with transverse colon. METHODS: From January 1999 to April 2001,
      we recruited seven patients (5 women and 2 men) who acquired esophageal stricture
      after swallowing hydrogen chloride or lye. The mean age of the patients was 42.7
      years. For surgery, the patients were placed in lithotomy position under single
      lumen intubated anesthesia. First, hand-assisted laparoscopic colon mobilization
      was performed with the assistance of the Harmonic Scalpel (AutoSuture Company,
      Norwalk, CT, USA) through a 7-cm upper abdominal incision. Then using cervical
      esophagocolostomy through the retrosternal route, coloenterostomy and
      colocolostomy were achieved. RESULTS: The mean operative time was 3.9 h (range,
      3.2-5 h). The mean hospital stay was 9.1 days (range, 8-13 days). Mean blood loss
      was 100 ml (range, 50-350 ml). All the patients obtained successful outcomes.
      There was one mild abdominal wound infection, and no surgical mortality. At this
      writing, the seven patients can eat solid food very well after a mean follow-up
      period of 18.2 months. CONCLUSIONS: Hand-assisted laparoscopic colonic
      mobilization for esophageal reconstruction is a safe and feasible operation for
      treating patients with esophageal stricture.

PMID- 12239652
TI  - [Positron emission tomography for the preoperative staging of esophageal
      carcinoma].
AB  - BACKGROUND AND OBJECTIVE: Exact preoperative staging is a prerequisite for the
      indication as well as the choice of the appropriate operative technique for
      patients with esophageal carcinoma. In this prospective study we assessed whether
      positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) increases
      the accuracy of staging compared to standard computer tomography (CT) and leads
      to a different therapeutic approach. PATIENTS AND METHODS: 30 patients (25 men, 5
      women, median age 63 years) with histologically identified carcinoma of the
      esophagus (n =29) and the cardia (n = 1), respectively, were studied. All
      patients underwent FDG-PET imaging of the neck, chest, and abdomen as well as CT
      of the chest and abdomen. Sensitivity, specificity and accuracy were calculated
      for FDG-PET and CT to evaluate the detection of histologically identified lymph
      node metastases and distant metastatic disease. RESULTS: FDG-PET showed higher
      specificity whereas the accuracy of the CT proved to be higher not only for the
      detection of abdominal lymph node metastases (67 % vs. 46 %), but also for lymph
      node metastases of the thorax (71 % vs. 50 %). Furthermore, the accuracy of the
      CT for the detection of blood-bone and lymphatic distant metastases was also
      higher than that of FDG-PET (72 % vs. 68 %). FDG-PET was more specific (100 % vs.
      71 %) albeit less sensitive than CT-imaging (27 % vs. 73 %). CONCLUSION: In our
      study, FDG-PET did not increase the accuracy of standard staging (CT) in patients
      with carcinoma of the esophagus. Therefore, no new consequences resulted for the
      operative indication as well as therapeutic procedure. Due to the high costs
      involved with PET investigation, this form of staging is momentarily indicated
      mainly for use in clinical studies, and in cases where CT does not offer
      unequivocal results. Increase in sensitivity of the already advantageous whole
      body FDG-PET imaging by means of tumor-affinitive radiopharmaceuticals as well as
      optimized apparatus resolution could lead to new indications for this staging
      procedure.

PMID- 12239653
TI  - [Comorbidity in narcoleptic patients].
AB  - BACKGROUND AND OBJECTIVE: Narcolepsy is a rare disease which remains undiagnosed
      in 90 %. The international literature so far has paid little attention to
      comorbid disorders. PATIENTS AND METHODS: In preparation for a German Narcolepsy
      Register this pilot study evaluated data from hospital records of 106 narcolepsy
      patients (60 men, 46 women, 8-83 years, mean 45.1 years) retrospectively
      emphasising comorbid diseases. RESULTS: The parasomnias sleepwalking and
      nightmares were 6 times as frequent as in the general population. With respect to
      the HLA findings the extremely high frequency of REM behavior disorder
      contributes to the assumption of a common pathomechanism. Obstructive sleep apnea
      and periodic limb movement disorder (PLMD) occurred much less than described in
      literature, while the results on obesity, headache and depression are in line
      with published findings. CONCLUSION: Diagnosis of one of these comorbid disorders
      should always be followed by thorough investigation for symptoms of narcolepsy i.
      e. excessive daytime sleepiness, sleep attacks and cataplexy.

PMID- 12239655
TI  - [Liver damage caused by drugs].

PMID- 12239654
TI  - [Osteomyelitis of the tibial head caused by Mycobacterium haemophilium in a
      patient with AIDS].
AB  - HISTORY AND ADMISSION FINDINGS: A 53-year-old man with known HIV infection and
      AIDS was admitted because of painful swelling at the right knee for 6 weeks. The
      cause was thought to be osteomyelitis and surgical treatment was planned.
      INVESTIGATIONS: No causative pathogen was found at curettage and lavage of an
      abscess at the right medical head of the tibia, but at a subsequent operative
      revision acid-fast rods were seen and identified as Mycobacterium haemophilum.
      TREATMENT AND COURSE: A systemic antibiotic, 1 g levofloxacin daily, had been
      started at the initial abscess operation. 2 weeks later, because swelling of the
      right knee had recurred with marked local and systemic signs of infection, a
      second surgical intervention was performed. Afterwards, in view of the
      histological finding of acid-fast bacteria suggesting tubercular osteomyelitis,
      the patient was put on combined treatment with 300 mg/d of isoniazid, 1600 mg/d
      of ethambutol, 2 g/d of pyrazinamide, and 1 g of streptomycin i.m. every other
      day. After molecular microbiological identification of M. haemophilum the
      antibiotic treatment was changed to 1600 mg/d of ethambutol, 300 mg/d of
      rifabutin and 1 g/d of clarithromycin. The operation wound healed well.
      CONCLUSION: M. haemophilum infection can be lethal in immunodeficient patients if
      untreated. Although there is no standard treatment, this rare infectious disease
      responds relatively well to a modified combined tuberculostatic regimen. Special
      laboratory techniques to identify the specific causative pathogen are therefore
      of great importance.

PMID- 12239656
TI  - [Cardiological diagnosis in patients with obstructive sleep apnea].

PMID- 12239657
TI  - [Obstruction of the iliac artery: course, therapy, complications].

PMID- 12239658
TI  - [Familial hypolipoproteinemia with liver steatosis].

PMID- 12239659
TI  - [Driving despite residual paresis in the arm?].

PMID- 12239660
TI  - [The lactate-ischemia test: efficient for diagnosis of myopathy?].

PMID- 12239661
TI  - [Brachytherapy and "evidence based medicine": we must wait longer for the
      solution].

PMID- 12239662
TI  - [Is there a classification of degrees of severity for a restrictive respiratory
      disorder?].

PMID- 12239663
TI  - The debate over hand transplantation.

PMID- 12239664
TI  - A position statement in support of hand transplantation.
AB  - The scientific basis for human trials of hand transplantation was both
      experimental and clinical. Prolonged survival of limb transplants was achieved in
      small and large animals by using novel immunosuppressive drugs. Further, all
      tissue components of the hand (skin, muscle, tendon, nerve, bone, and joint) were
      individually transplanted with success in humans. After appropriate institutional
      review of the ethics, experimental data, treatment protocol, and informed
      consent, clinical trials were approved. Thirteen hands have been transplanted
      onto 10 recipients, with resultant low morbidity and no mortality. With the
      exception of one recipient who requested amputation after the second year,
      results of hand transplantation have been highly successful. Functional return
      mirrored that seen after hand replantation. The limbs were progressively
      integrated into activities of daily living and professional tasks. The hand and
      patient survival rate exceeds the initial results of any previously transplanted
      organ. This success strongly supports continuation of these human trials.

PMID- 12239665
TI  - Concerns about human hand transplantation in the 21st century.
AB  - The decision to perform a human hand transplant was justified perhaps on less
      than an ideal scientific basis-only approximately 60 rat limb transplants and 2
      primate limb transplants have survived for longer than 200 days and only 8 of 19
      pig limb osteomyocutaneous transplants showed no signs of rejection at 90 days.
      It seems unlikely that the survival of a human hand transplant will be any better
      than the survival of a kidney transplant, which has a half-life of approximately
      7.5 to 9.5 years. Fourteen hand transplants, however, have now been performed in
      11 humans with the skin component of 1 remaining viable up to 3 years after
      surgery. Intermittent episodes of acute rejection seem to have been relatively
      simple to reverse by temporarily increasing the dose of immunosuppressive agents
      and steroids. Chronic rejection has occurred in 1 patient, necessitating re
      amputation of the transplanted hand. Active range of motion of the digits has
      been surprisingly better than would have been expected based on previous results
      of replantation, but return of sensibility has been less than optimal. The
      immunosuppression has been well tolerated without any major medical problems or
      life-threatening episodes, but some patients have developed chronic viral and
      fungal infections and several have developed posttransplant diabetes.
      Extrapolating from the previous experience of solid-organ transplants, chronic
      immunosuppression may predispose a hand transplant patient to an 80% chance of
      developing an infection, a 20% potential risk of developing posttransplant
      diabetes, and a 4% to 18% potential risk of developing a malignancy. Even though
      there is universal agreement that composite tissue allograft transplantation will
      become the ultimate reconstructive option, no one can predict the eventual role
      of hand transplantation in the future, but perhaps an international database of
      these hand transplant patients should be established so that independent
      reviewers can more objectively evaluate their functional outcome, the incidence
      of chronic rejection, and the risks of long-term immunosuppression.

PMID- 12239666
TI  - Collagen as a clinical target: nonoperative treatment of Dupuytren's disease.
AB  - The cellular events leading to abnormal synthesis of collagen are important to
      our understanding of pathologic processes leading to impaired joint function. The
      contracture of Dupuytren's disease is a notable example. In a series of
      controlled phase-2 clinical trials, excessive collagen deposition in Dupuytren's
      disease has been targeted by a unique nonoperative method using enzyme
      (Clostridial collagenase) injection therapy to lyse and rupture finger cords
      causing metacarpophalangeal and/or proximal interphalangeal joint contractures.
      Forty-nine patients were treated in a random, placebo-controlled trial of one
      dose of collagenase versus placebo at one center. Subsequently 80 patients were
      treated in a random, placebo-controlled, dose-response study of collagenase at 2
      test centers. The results of these studies indicate that nonoperative collagenase
      injection therapy for Dupuytren's disease is both a safe and effective method of
      treating this disorder in the majority of patients as an alternative to surgical
      fasciectomy. Phase-3 efficacy trials are now being planned to further develop and
      test this method under Food and Drug Administration regulatory guidelines. The
      findings of our study may lead to simpler and less invasive nonoperative
      treatments of joint limitation in which collagen plays a major pathologic role.

PMID- 12239667
TI  - Long-term results of surgical management of proximal interphalangeal joint
      contracture.
AB  - To evaluate the long-term results of surgical treatment of proximal
      interphalangeal (PIP) joint contractures, 68 PIP joints were retrospectively
      reviewed with a minimum follow-up period of 24 months. Preoperative and
      intraoperative factors were studied for outcomes and subjected to statistical
      analysis. Among the total group the average improvement was 7.5 degrees. When
      grouped by diagnosis into simple (less severe diagnoses) and complex (more severe
      diagnoses) the average degrees gained were 17.2 degrees and 0.5 degrees,
      respectively. The statistically significant factors that were identified that
      affected results were age, number of prior procedures, preoperative flexion,
      removal of an exostosis, number of structures addressed, and preoperative arc of
      motion. The second surgery (joints requiring repeat release or salvage procedure)
      rates were 35% overall, 29% simple, and 39% complex; the difference was not
      significant. The best surgical candidate is a patient younger than 28 years with
      a less severe diagnosis and who has preoperative maximum flexion measurement < 43
      degrees.

PMID- 12239668
TI  - Vascular anatomy of the human flexor digitorum profundus tendon insertion.
AB  - The vascular anatomy of the flexor digitorum profundus (FDP) tendon insertion is
      described by using a vascular injection and modified Spalteholtz tissue clearing
      protocol in 36 human cadaver digits. A consistent dense palmar and dorsal
      vascular supply to the tendon at its insertion into the distal phalanx was
      observed based on sources from both the distal phalanx and the vinculum brevis
      profundus. Multiple palmar-dorsal vascular interconnections were seen between
      these spatially distinct vascular networks, a finding not observed previously in
      studies of the vascular anatomy of tendon or ligament insertions. Additionally a
      well-defined dorsal zone of hypovascularity was identified subjacent to the volar
      plate of the distal interphalangeal joint, within 1 cm of the tendon insertion.
      Recognition of the vascular supply to the FDP insertion at the distal phalanx
      permits further evaluation of the vascular, histologic, and cellular events after
      FDP tendon avulsion and improves the understanding of the biologic response
      mechanisms involved in bone-tendon healing.

PMID- 12239669
TI  - The extensor pollicis brevis entrapment test in the treatment of de Quervain's
      disease.
AB  - Isolation of the extensor pollicis brevis (EPB) tendon in a separate compartment
      has been reported to contribute to the pathogenesis of de Quervain's disease and
      affect the patient's response to nonsurgical treatment. The EPB entrapment test
      was developed to evaluate the patient with de Quervain's disease. The purpose of
      this study was to compare the results from this preoperative test with the
      anatomic findings at surgery in patients who failed nonsurgical treatment. One
      hundred seventy-eight patients who were treated for de Quervain's disease (200
      wrists) were asked to compare the amount of pain elicited by firm resistance with
      thumb metacarpophalangeal joint extension with that from resistance to palmar
      abduction. Twenty-six wrists (13%) had surgical release after failure of
      nonsurgical treatment. Of those having surgery the proportion of wrists with a
      positive EPB entrapment test was significantly higher among those with 2
      compartments (18 of 22) than among those with 1 compartment (0 of 4) (Fisher's
      exact test). In the surgical group the EPB entrapment test showed 81% sensitivity
      and 50% specificity in identifying wrists with a separate EPB compartment.

PMID- 12239670
TI  - Pseudomallet finger associated with exostosis of the phalanx: a report of 2
      cases.
AB  - An exostosis around the distal interphalangeal joint can cause finger deformity
      that resembles mallet finger. We report 2 cases of pseudomallet finger associated
      with exostosis, both of which were successfully treated with bone resection.

PMID- 12239671
TI  - Surgical technique to reduce scar discomfort after carpal tunnel surgery.
AB  - A total of 379 patients (416 hands) with clinically diagnosed and
      electromyographically confirmed carpal tunnel syndrome were enrolled in a
      prospective study to determine the influence of a modified open decompression
      technique on postoperative scar discomfort. The new technique used in 184
      patients (200 hands) is presented. Special attention was focused on
      identification and preservation of macroscopically detectable subcutaneous
      nerves. After using this method, which permits complete visualization of the
      entire transverse carpal ligament, the incidence of postoperative scar discomfort
      was 2.5%. This was significantly lower compared with the group of 195 patients
      (216 hands) treated by standard open decompression technique, without
      preservation of subcutaneous nerves. Primary results regarding relieving symptoms
      were comparable in both groups. Five anatomic variations of subcutaneous
      innervation, at the site of the incision in the line with the radial border of
      the ring finger, are described. The etiology of scar discomfort is discussed.

PMID- 12239672
TI  - Enabling meta-analysis in systematic reviews on carpal tunnel syndrome.
AB  - Possible solutions to the problems of clinical heterogeneity of outcome measures
      and inadequate reporting of results for randomized controlled trials (RCTs) on
      carpal tunnel syndrome (CTS) are presented. Meta-analysis was impeded by these
      problems in 2 systematic reviews concerning conservative and surgical treatment
      options for CTS. A solution to the problem of inadequate data presentation is to
      add explicit information on minimal requirements with regard to data presentation
      to guidelines for the reporting of studies. To resolve the problem of clinical
      heterogeneity of the outcomes there should be consensus on the (validated)
      outcomes that should be used in RCTs. For CTS there is little evidence available
      on the reliability, validity, and responsiveness to change of the commonly used
      outcomes in RCTs. Resolving both problems will increase the comparability of
      RCTs, enabling the calculation of a pooled estimate of effect in a meta-analysis.

PMID- 12239673
TI  - Analgesic benefit, functional outcome, and patient satisfaction after partial
      wrist denervation.
AB  - Partial wrist denervation is a useful palliative procedure for chronic wrist pain
      when reconstructive procedures are not feasible or desirable. We reviewed 19
      patients who had 20 isolated anterior and posterior interosseous neurectomies
      with no previous or concurrent wrist surgery in a 5-year period at our
      institution. At an average of 2.5 years postoperatively, 80% of patients reported
      a decrease in pain, 45% reported normal or increased grip strength, and 73% of
      employed patients had returned to work. Three patients required additional
      procedures for pain relief (2 arthrodesis, 1 radial styloidectomies). Failure
      tended to occur in the first postoperative year. Poor preoperative range of
      motion and workers' compensation status were predictive of failure. Failure also
      occurred in the single patient with rheumatoid arthropathy. Two patients had
      subsequent arthrodeses. There were no complications related to the surgery.
      Overall, 85% of patients reported satisfaction with this procedure; 90%
      retrospectively would choose the same treatment for their chronic wrist pain.
      Partial denervation of the wrist via the anterior and posterior interosseous
      nerves is a technically easy procedure and may provide pain relief sufficient to
      markedly delay the need for more extensive salvage procedures in patients with
      wrist arthritis.

PMID- 12239674
TI  - Injury to the dorsal sensory branch of the ulnar nerve in the arthroscopic repair
      of ulnar-sided triangular fibrocartilage tears using an inside-out technique: a
      cadaver study.
AB  - This anatomic study of the commonly described inside-out Tuohy needle technique
      was performed to better define the course of needle passage relative to the
      anatomic structures in this region including the dorsal sensory branch of the
      ulnar nerve (DBUN) and extensor carpi ulnaris (ECU) tendon. Ten fresh-frozen
      cadaver specimens had arthroscopic-guided passage of a Tuohy needle through the
      triangular fibrocartilage (TFC). Dissection of the ulnar side of the wrist was
      performed and various measurements were recorded. The average minimum distance
      between suture A (the suture closest to the nerve) and the DBUN was 1.9 mm. The
      average minimum distance between suture B and the DBUN was 2.7 mm. The distance
      between the 2 sutures at the level of the capsule averaged 6.2 mm. The distance
      between the DBUN and the ECU averaged 7.2 mm. In 5 of 10 specimens the sutures
      exited on opposite sides of the DBUN. The DBUN is variable in its course but in
      every case it passes in close proximity to the sutures that exit the ulnar side
      of the wrist in arthroscopic repair of ulnar-sided TFC tears.

PMID- 12239675
TI  - Biomechanical analysis of two ulnar head prostheses.
AB  - The biomechanical effectiveness of 2 ulnar head prostheses was evaluated in 5
      fresh-frozen cadaver arms. By using electromagnetic sensors, the amount of
      forearm rotation, diastasis, and dorsal/palmar subluxation of the radius at the
      level of the sigmoid notch was measured with the forearm in neutral rotation,
      pronation, and supination with and without dorsal/palmar loading. Testing was
      done in the intact specimens and after insertion of 2 types of ulnar head
      prostheses. Dynamic forearm rotation was also achieved by applying loads in the
      line of action of the appropriate pronator or supinator muscles to obtain a
      centroidal path of the radius relative to the ulna. Overall after ulnar head
      replacement forearm rotation lessened in pronation, diastasis decreased in most
      forearm positions, and subluxation increased in supination compared with the
      intact specimen. Despite these changes, both prostheses maintained near-normal
      biomechanics of the distal radioulnar joint when compared with the irregular
      behavior occurring after distal ulna resection. Therefore these prostheses are
      suggested for restoration of distal radioulnar joint function.

PMID- 12239676
TI  - Kinematic analysis of the distal radioulnar joint after a simulated progressive
      ulnar-sided wrist injury.
AB  - A kinematic analysis of a progressive, ulnar-sided wrist injury was performed
      using a cadaver model to study the static and dynamic stabilizers of the distal
      radioulnar joint with a 3-dimensional motion tracking system. Anatomically based
      loads were applied to achieve pronation and supination and then the specimens
      were evaluated after serial transection of the triangular fibrocartilage, the
      extensor carpi ulnaris sheath, and the ulnocarpal ligaments. Statistically
      significant increases in translation of the radius relative to the ulna occurred
      with sectioning of both the triangular fibrocartilage proper and the extensor
      carpi ulnaris tendon sheath. No significant change in position of the forearm
      could be appreciated with subsequent sectioning of the ulnocarpal ligaments. Our
      observations support the idea that the ulnocarpal ligaments do not need to be
      surgically reconstructed when there are serious injuries to the triangular
      fibrocartilage complex.

PMID- 12239677
TI  - Radiographic analysis of pisotriquetral joint and pisiform motion.
AB  - We evaluated 45 wrists of normal volunteers fluoroscopically (15) and
      radiographically (30) to determine the optimal radiographic technique for
      profiling the pisotriquetral (PT) joint and to assess the pisiform motion. Real
      time fluoroscopy showed that 4 views are necessary for optimal PT joint and
      pisiform visualization: wrist neutral/30 degrees forearm supination, wrist
      extension/30 degrees forearm supination, and active plus passive wrist flexion/45
      degrees forearm supination with thumb abduction. Excursion percentage of the PT
      articular surface apposition on video imaging occurred 10% proximally in neutral,
      20% distally in extension, and 40% proximally in flexion. Radiography showed
      pisiform excursion distally (2.5 mm) in extension and proximally with active (3
      mm) and passive (2 mm) flexion. Pisotriquetral angle opened proximally (15
      degrees ) in extension and distally with active (10 degrees ) and passive (5
      degrees ) flexion. Pisotriquetral space averaged 1.5 mm in neutral, 1 mm in
      extension, 3.5 mm in active, and 3 mm in passive flexion. Pisohamate distance
      averaged 7.5 mm in neutral, increased to 8 mm in extension, and decreased to 2 mm
      with active and 0 mm with passive flexion. These views and parameters are useful
      for evaluating patients with PT joint injury and disease.

PMID- 12239678
TI  - Enchondromas of the hand: treatment with curettage and cemented internal
      fixation.
AB  - Removal by means of curettage is the mainstay of surgical treatment of
      enchondromas of the hand. Reconstruction traditionally entails filling the tumor
      cavity with a bone graft, or it may be decided not to perform a reconstruction.
      In either case a period of protected activity is needed until the tumor cavity
      has healed. The current study describes the use of cemented internal fixation for
      the purpose of reconstruction of these cavities. This technique provides
      immediate mechanical stability and allows early mobilization. Between 1986 and
      1999, we treated 13 patients who were diagnosed as having enchondroma of the
      hand. Surgery included tumor removal with hand curettes and high-speed burr
      drilling. The remaining tumor cavity was reconstructed by using bone cement and
      intramedullary hardware. All patients were followed-up for more than 2 years.
      There were no postoperative infections or fractures, and all patients returned to
      their presurgical functional capability within 4 weeks. At the most recent follow
      up evaluation, none of the patients had local tumor recurrence. Although 7
      patients had a decrease in flexion of the metacarpophalangeal or interphalangeal
      joints, none reported a functional limitation. Reconstruction of the tumor cavity
      with cemented hardware provides immediate mechanical stability, allows early
      mobilization, and is associated with good functional outcome.

PMID- 12239679
TI  - Renal cell carcinoma with metastases to the triquetrum: case report.
AB  - Metastatic tumors of the hand are rare, with fewer than 200 cases reported in the
      literature. Renal cell carcinoma is among the most common tumors to metastasize,
      but we are not aware of reports of this tumor metastasizing to the carpal bones.
      We describe a case of renal cell carcinoma that metastasized to the triquetrum to
      draw attention to the potential for such lesions developing within the hand and
      wrist.

PMID- 12239680
TI  - Intrarater and interrater reliability of the Eaton classification of basal joint
      arthritis.
AB  - The Eaton classification is a radiographic rating used to define the severity of
      basal joint arthritis. Despite widespread use, the intrarater and interrater
      reliability has never been determined. Seven men and 33 women, mean age 60 years
      (range, 31-88 y) were clinically diagnosed with basal joint arthritis. Forty
      radiographs of these patients' basal joints (21 right and 19 left) were staged
      according to Eaton, stages I through IV. Three hand surgeons with a Certificate
      of Added Qualification and 3 orthopedic surgical residents reviewed the films on
      2 separate occasions at least 1 week apart. The results of intrarater and
      interrater reliability were assessed by using kappa statistical analysis, with
      results classified as poor (0-.50), moderate (.51-.75), or excellent (>.75). The
      overall mean intrarater and interrater reliability was moderate,.657 and.529,
      respectively. The hand surgeons' intrarater reliability (.666) was slightly
      better than the residents (.648). There was a greater difference in the mean
      interrater reliabilities among the hand surgeons (.601) than the orthopedic
      residents (.487). These results are similar to those found when other orthopedic
      radiographic classifications have been evaluated for interrater and intrarater
      reliability.

PMID- 12239681
TI  - The influence of wrist position on individual finger forces during forceful grip.
AB  - Nine healthy subjects sustained maximum grip of an instrumented handle while
      voluntarily moving the wrist joint within their available range of motion of the
      wrist in a continuous and random manner. Individual finger forces and wrist
      angular positions in flexion/extension and radial/ulnar deviation were recorded
      simultaneously. Wrist position had a significant effect on individual finger
      force and total force production. Peak finger forces were produced at 20 degrees
      of wrist extension and 5 degrees of ulnar deviation. At this position, a mean
      total grip force of 114.9 (+/-12.8) N was produced with force-sharing percentages
      of 32.2% (+/-3.8%), 32.6% (+/-4.3%), 23.5% (+/-4.5%), and 11.7% (+/-4.9%) among
      the index, middle, ring, and small finger, respectively. As the wrist was moved
      farther away from this position, the forces produced by individual fingers
      decreased incrementally; however, the decreases in individual finger forces were
      not proportional, leading to a dependence of finger force-sharing patterns on
      wrist position.

PMID- 12239682
TI  - Hand size influences optimal grip span in women but not in men.
AB  - This study investigates which position (grip span) on the standard grip
      dynamometer results in maximum grip strength. Our null hypotheses included (1) no
      optimal grip span exists for measuring grip strength and (2) optimal grip span is
      unrelated to hand size. We also intended to derive a simple mathematical
      algorithm to adapt grip span to hand size. Seventy healthy subjects (40 women/30
      men; mean age, 40 years; range; 20-80 years) free of upper-limb lesions were
      evaluated. Each hand was randomly tested on 10 occasions using 5 different grip
      spans. Our findings showed that (1) optimal grip span was identified for both
      genders and (2) hand size and optimal grip span correlated in women but not in
      men. When measuring handgrip strength in women, hand size must be taken into
      consideration. We provide a mathematical equation (y = x/5 + 1.5 cm) to adapt
      optimal grip span (y) to hand size (x) in women. In adult men, optimal grip span
      can be set at a fixed value (5.5 cm).

PMID- 12239683
TI  - Self-reinforced bioabsorbable versus metallic fixation systems for metacarpal and
      phalangeal fractures: a biomechanical study.
AB  - Bioabsorbable fixation devices offer a useful option to treat small bone
      fractures of the hand if the prerequisite of reliable and stable osteofixation is
      met. We compared the stabilities of various bioabsorbable fixation devices with
      metallic fixation devices by using an oblique osteotomy model in radial to ulnar
      orientation. The 1.5-mm, self-reinforced, poly-L-lactide (SR-PLLA) pins provided
      fixation rigidity comparable with 1.5-mm K-wires in dorsal and palmar apex
      bending, whereas in lateral apex bending and in torsion the rigidity was equal to
      that of 1.25-mm K-wires. The 2.0-mm, self-reinforced, poly-L/DL-lactide (SR
      P(L/DL)LA) 70/30 screws provided rigidity comparable with that of 1.5-mm K-wires
      in all testing modes. The bioabsorbable plate considerably enhanced the bending
      stabilities of the fixation system, but a single interfragmentary screw provided
      only limited rotational rigidity. The results show that by using ultra-high
      strength self-reinforced implants adequate fixation stability for hand fracture
      fixation can be achieved.

PMID- 12239684
TI  - Thumb metacarpophalangeal joint arthrodesis using the AO 3.0-mm cannulated screw:
      surgical technique.
AB  - A technique for metacarpophalangeal joint arthrodesis of the thumb using the 3.0
      mm AO cannulated screw is described. Advantages of this technique include its
      relative simplicity and accuracy, solid fixation, and high union rate.

PMID- 12239685
TI  - An unusual supracondylar process syndrome.
AB  - We report a case of a supracondylar process that was located beneath the
      neurovascular bundle and caused tenting of the bundle with elbow extension and
      supination.

PMID- 12239686
TI  - Apparent inconsistency regarding the nomenclature of the branches of the radial
      nerve near the elbow.

PMID- 12239687
TI  - Wedge osteotomies of the radius for Kienbock's disease.

PMID- 12239689
TI  - Position in bed is associated with left or right location in benign paroxysmal
      positional vertigo of the posterior semicircular canal.
AB  - PURPOSE: To determine if position during bedrest is related to the canal affected
      in posterior canal benign paroxysmal positional vertigo (BPPV). MATERIALS AND
      METHODS: Fifty-five individuals with posterior canal BPPV were investigated.
      Diagnosis was established if a consistent clinical history was found with vertigo
      and induced positional nystagmus elicited on the Dix-Hallpike test (DHT).
      Preference for left or right position during bed rest was determined before
      performing the DHT. All patients were treated by a single particle repositioning
      procedure, and relapses were investigated at the seventh and 30 days
      posttreatment. RESULTS: Forty-five individuals always slept on the same side (29
      on the right, 16 on the left side), and 10 patients preferred to change sides
      during bed rest. Among those patients able to maintain a constant position during
      bed rest, 27 and 18 presented a positive DHT on the right and left sides,
      respectively. The canal affected was found to be significantly associated with
      side during bed rest (relative risk = 2.75; P = 0.01, Fisher exact test). DHT was
      negative in 86% of patients at 30 days. No differences were found between
      individuals who presented a constant position in bed and those who changed
      positions. CONCLUSIONS: Lateral supine position during bed rest is associated
      with the canal affected in BPPV. We speculate that gravity might facilitate the
      deposition of particulate material on the posterior semicircular near the ampulla
      canal during bed rest.

PMID- 12239690
TI  - Low-dose dexamethasone reduces nausea and vomiting after tympanomastoid surgery:
      a comparison of tropisetron with saline.
AB  - PURPOSE: The aim of the study was to evaluate the efficacy of low-dose
      dexamethasone sodium phosphate (5 mg) on the prophylaxis of nausea and vomiting
      after tympanomastoid surgery. Tropisetron hydrochloride (2 mg) and saline were
      used as controls. MATERIALS AND METHODS: One hundred twenty patients (n = 40 in
      each of 3 groups) undergoing general anesthesia for tympanomastoid surgery were
      enrolled in this randomized, double-blind, placebo-controlled study. Following
      endotracheal intubation, group 1 received intravenous dexamethasone 5 mg, whereas
      groups 2 and 3 received intravenous 2 mg tropisetron and saline, respectively.
      Several parameters connected with the occurrence of postoperative nausea and
      vomiting were evaluated. RESULTS: Dexamethasone 5 mg significantly reduced the
      total incidence of nausea and vomiting by 40% (P =.002). Dexamethasone also
      reduced the incidence of vomiting episodes by more than 4-fold (P =.03) and the
      incidence of patients requiring rescue antiemetics (P =.02). Tropisetron at a 2
      mg dose did not exhibit any significant antiemetic effect. CONCLUSIONS:
      Dexamethasone sodium phosphate 5 mg was more effective than 2 mg tropisetron
      hydrochloride and saline in the prevention of nausea and vomiting after
      tympanomastoid surgery.

PMID- 12239691
TI  - Intranasal laser-assisted dacryocystorhinostomy with the use of a surgical
      microscope.
AB  - PURPOSE: Obstruction of the nasolacrimal duct is a serious chronic condition,
      treatment for which has not yet been successfully resolved. Several methods have
      been proposed for the management of chronic epiphora. A modified method of
      intranasal laser-assisted dacryocystorhinostomy with the use of a surgical
      microscope is described. MATERIALS AND METHODS: The procedure is a modification
      to the West and Veis-Claus-Guttich method. The primary and late results of this
      method are presented for 53 patients over the past 7 years with chronic epiphora
      caused by stenosis of the nasolacrimal duct. Selection criteria included chronic
      epiphora, nasolacrimal duct stenosis due to Down syndrome, empyema of the
      lacrimal sac, and recurrence from previous operations. Patients were operated on
      under general anesthesia. RESULTS: Fifty-one patients (96.3%) were free of
      symptoms postoperatively (mean follow-up time, 6 months). CONCLUSION: The
      simplicity of this method compared with traditional methods is correlated with
      excellent postoperative results and patient satisfaction.

PMID- 12239693
TI  - Endoscopic and KTP laser-assisted surgery for juvenile nasopharyngeal
      angiofibroma.
AB  - Juvenile nasopharyngeal angiofibroma is a highly vascular tumor arising from the
      area around the sphenopalatine foramen. Various radical and extended radical
      surgeries have been advocated to surgically excise both extranasopharyngeal and
      nasopharyngeal juvenile angiofibromas. However angiofibromas involving the
      nasopharynx, nose, and sphenoid with minimal lateral extension via the
      sphenopalatine foramen can also be adequately managed endoscopically either alone
      or with 1 of the traditional approaches. Nine cases of juvenile nasopharyngeal
      angiofibroma were successfully managed between January, 1999, and March, 2001, by
      preoperative selective embolization of the internal maxillary artery with or
      without external carotid artery clamping, followed by endoscopic excision. Two of
      the 9 cases underwent KTP/532 laser-assisted endoscopic excision, whereas the
      transpalatal approach was used along with the endoscope in another 2 cases. The
      patients remained free of disease after a median follow-up period of 17 months.
      We report our preliminary experience in endoscopic and KTP laser-assisted
      excision of juvenile nasopharyngeal angiofibroma.

PMID- 12239692
TI  - Early oral feeding following total laryngectomy.
AB  - INTRODUCTION: Pharyngocutaneous fistula is one of the most common nonfatal
      laryngectomy complications (7.6% to 65% of all total patients). Preoperative
      radiotherapy, advanced tumor stage, poor preoperative medical status, and
      concomitant pharyngectomy are usually accepted causative factors in fistula
      formation. Delay of oral feeding is a common practice used by head and neck
      surgeons to prevent the development of pharyngocutaneous fistula. In this article
      we analyze our experience with special emphasis given to the early start of
      postoperative feeding. PATIENTS AND METHODS: The postoperative records of 48
      patients who had undergone total laryngectomy or total laryngopharyngectomy were
      reviewed. All patients were orally fed with water and clear liquids on the first
      postoperative day. The patients were closely observed at every feeding attempt,
      and if any sign of fistula was noted, a nasogastric tube was inserted.
      Preoperative radiotherapy, stage of disease, tumor differentiation, and
      pharyngectomy with total laryngectomy were statistically analyzed as potential
      risk factors contributing to fistula formation. The Fisher exact test was used to
      analyze the data. RESULTS: The overall pharyngocutaneous fistula rate was 12.5%
      in our series. The only statistically significant factor that increased the rate
      of fistula formation was resection of pharyngeal mucosa as an extension of total
      laryngectomy. Other parameters failed to show any statistical significance in
      development of this complication. CONCLUSION: Evaluation of fistula incidence in
      our series indicates that initiating oral feeding on the first postoperative day
      does not contribute to fistula formation. Additionally, the relatively shortened
      hospital stay and elimination of the psychologic and traumatic side effects of
      tube feeding are benefits of this approach that should be studied in further
      prospective quality-of-life studies.

PMID- 12239694
TI  - Isolated esthesioneuroblastoma of sphenoid sinus.
AB  - Esthesioneuroblastoma is a rare neuroendocrine tumor that arises from the
      olfactory epithelium and accounts for approximately 3% of all intranasal tumors.
      The tumor involvement in the nasal cavity with extension to paranasal sinuses,
      orbit, and anterior cranial fossa, is reported in the literature. In this report,
      we present an interesting case of isolated sphenoid sinus esthesioneuroblastoma,
      which is the first case to be reported in the literature, and discuss the
      pathology, clinical manifestations, and various treatment options for this tumor.

PMID- 12239695
TI  - CO(2) laser endolaryngeal microsurgery with the deflect tip of the pipe-guide
      handpiece.
AB  - Some regions of the larynx such as the inferior surface of the vocal fold and the
      subglottis cannot be adequately irradiated with a conventional laser instrument
      and a microscopic manipulator coupled to an operating microscope. To improve on
      this disadvantage, we present a method for CO(2) laser endolaryngeal microsurgery
      with the deflect tip of the pipe-guide handpiece. After exposure of the larynx, a
      pipe-guide handpiece with a deflective tip is inserted into the laryngeal cavity,
      and the lesion is vaporized and removed via direct laryngoscope observation under
      the microscope. With the deflect tip of the CO(2) laser pipe-guide handpiece, the
      laser beam can be irradiated vertical to the laryngeal mucosa, especially in
      regions such as the inferior surface of the vocal fold and the subglottic mucosa.
      The mucosa can be adequately vaporized with this laser instrument. This technique
      allows the surgeon to perform a precise, more hemostatic endoscopic operation
      with decreased postoperative edema. Disadvantages of this surgical procedure are
      that surgeons cannot perform a hands-off operation through the narrow operation
      field of the microlaryngoscope.

PMID- 12239696
TI  - Postirradiation malignant fibrous histiocytoma of the larynx: a case report.
AB  - A 63-year-old man presented with malignant fibrous histiocytoma of the larynx
      occurring 16 years after radiation treatment for squamous cell carcinoma of the
      larynx. Postirradiation sarcoma of the larynx is an unusual tumor. The location,
      the histopathologic and immunohistochemical appearance of the tumor, and the time
      elapsed since the initial treatment make it probable that this tumor is
      associated with prior radiation treatment. The possibility of postirradiation
      sarcomas after radiation therapy should not be a major factor influencing
      treatment decisions in the patients with head and neck cancer. Wide surgical
      resection of the tumor seems to be an efficient means in the management of this
      tumor.

PMID- 12239697
TI  - Polymorphous low-grade adenocarcinoma of the tonsil: report of a case and review
      of the literature.
AB  - Polymorphous low-grade adenocarcinoma (PLGA) is a relatively common malignancy of
      the oral cavity, representing 7% to 11% of all intraoral minor salivary gland
      tumors, and 19% to 26% of those that are malignant. However, it is a rare finding
      in the oropharynx, with only 6 cases reported in the medical literature. The
      clinical features of a case of PLGA of the tonsillar fossa in a 64-year-old
      gentleman are presented, only the second such case reported in the medical
      literature. A review and discussion of the literature pertaining to PLGA of the
      oral cavity and the oropharynx is provided. (Am J Otolaryngol 2002;23:297-299.

PMID- 12239698
TI  - Massive subcutaneous emphysema following percutaneous tracheostomy.
AB  - BACKGROUND: Bronchoscopic subcutaneous dilatational tracheostomy is fast becoming
      the method of choice for securing an airway in chronic ventilated patients in an
      intensive care setting. Many studies have demonstrated that it is a cost
      effective and safe procedure in experienced hands. Complications appear to be
      equivalent to those encountered in open tracheostomy. Subcutaneous emphysema
      following tracheostomy is a rare occurrence. Only 3 cases have been described
      following percutaneous dilatational tracheostomy. Management can be quite
      complex. MATERIAL AND METHODS: Retrospective review with case report of a patient
      with massive subcutaneous emphysema following percutaneous tracheostomy.
      CONCLUSION: Massive subcutaneous emphysema following percutaneous tracheostomy is
      a major complication that is rarely encountered. When due to a posterior tracheal
      wall tear, management consists of bypassing the laceration and allowing it to
      heal secondarily.

PMID- 12239699
TI  - QT prolongation and torsades de pointes associated with concurrent use of
      cisapride and erythromycin.
AB  - Prolongation of QT interval may lead to serious, potentially life-threatening,
      ventricular tachyarrhythmia, such as torsades de pointes. The cause may be an
      inherited or an acquired malfunction of ion channels at the myocardial cell
      membrane. Metabolic abnormalities, starvation, nervous system injury, and drug
      administration cause the much more frequent acquired long QT syndrome (LQTS).
      Types Ia and III antiarrhythmic drugs account for the majority of these life
      threatening events, whereas a number of drugs widely used in otolaryngology, such
      as antibiotics and antihistamines, have been recently implicated. A case of a
      life-threatening ventricular tachyarrhythmia after the concurrent administration
      of cisapride and erythromycin is presented. Reviewed are drugs commonly
      prescribed in otolaryngology, as well as the associated risk factors that
      potentially lead to LQTS.

PMID- 12239700
TI  - Nasopharyngeal amyloidosis.
AB  - PURPOSE: To discuss the presentation of localized amyloidosis affecting the
      nasopharynx and discuss the management options. Amyloidosis in the head and neck
      is a rare and benign condition that usually takes the form of localized
      amyloidosis. Because systemic amyloidosis markedly shortens life expectancy owing
      to its involvement with vital organs, rectal biopsy or fat aspiration of the
      anterior abdominal wall must be carried out to exclude systemic involvement.
      Localized amyloidosis in the head and neck can involve the orbit, sinuses,
      nasopharynx, oral cavity, salivary glands, and larynx. METHODS: We present the
      case of a patient with conductive hearing loss and serous otitis media with
      effusion secondary to nasopharyngeal amyloidosis, as well as present a review of
      the literature. RESULTS: Only a few cases of nasopharyngeal amyloidosis have thus
      far been reported. Patients with this disease can also present with recurrent
      epistaxis, postnasal drip, nasal obstruction, and eustachian tube dysfunction.
      Localized amyloidosis of the nasopharynx, which is slow growing, has proved
      difficult to treat because it can persist or recur despite surgical treatment.
      Furthermore, bleeding may be a major complication in treating patients with
      nasopharyngeal amyloidosis by transpalatal excision because the amyloid deposits
      cause vascular wall fragility. Finally, there is no evidence that surgical
      treatment of nasopharyngeal amyloidosis can prolong survival or that localized
      amyloidosis can progress to systemic amyloidosis. For these reasons, we elected
      to treat our patient with a tympanostomy tube and observation. CONCLUSION: In the
      absence of systemic disease, localized amyloidosis of the nasopharynx may be
      treated conservatively.

PMID- 12239701
TI  - Endonasal endoscopic treatment of medial orbital wall fracture via rotational
      repositioning.
AB  - Various surgical approaches have been employed to treat the medial orbital wall
      fracture. It has been necessary to use grafts or splints in these approaches. We
      introduced a new technique to treat our patient with diplopia resulting from
      medial orbital fracture. In this new method, rotational repositioning of the
      fractured segment eliminates the use of any graft or synthetic material in the
      nose, ethmoid sinuses, or the orbit. The procedure could be done under local
      anesthesia, which facilitates intraoperative monitoring of the ocular movements
      to evaluate improvement of diplopia. Rotational repositioning technique could be
      an effective alternative method to previous approaches in treatment of selected
      medial orbital wall fractures.

PMID- 12239702
TI  - Solitary plasmacytosis of the larynx in a patient with non-Hodgkin's lymphoma.
AB  - Solitary plasmacytosis of the larynx is a clinically unusual event. It may cause
      hoarseness or airway obstruction and usually needs surgical excision.
      Plasmacytosis is distinguished from extramedullary plasmacytoma (EMP) in that the
      latter primarily involves the head and neck and needs more intensive therapy such
      as radiotherapy. Many reports have described the histopathology and
      immunohistochemistry of EMP of the larynx; however, no literature in English has
      described solitary plasmacytosis of the larynx. We report a 44-year-old female
      patient with non-Hodgkin's lymphoma and systemic lupus erythromatosus with
      Sjogren's syndrome. She complained of 1-year period of hoarseness that became
      exacerbated in the most recent 3 weeks. A wide-base and smooth-surface mass at
      the left supraglottic area was noted by direct laryngoscope. Computed tomography
      scan revealed a well-defined radiopaque mass. The histopathology of a specimen
      excised by carbon dioxide laser-assisted laryngomicrosurgery was interpreted
      initially as plasmacytoma. Immunohistochemical staining for kappa and lambda
      light chains demonstrated polyclonal plasma cells, and the definitive diagnosis
      was plasmacytosis. After 6 months follow-up, the subjective quality of her voice
      improved. Laryngoscopic examination revealed no evidence of recurrence.

PMID- 12239703
TI  - Mucosal melanoma of the sinonasal tract.
AB  - Mucosal melanoma of the sinonasal tract is an uncommon clinical entity, which
      frequently presents in advanced stages and follows an unpredictable course. We
      describe a case of a 97-year-old white female who presented with a 5-month
      history of painless, intermittent epistaxis and who was found to have melanoma
      involving the right inferior turbinate. She required operative intervention
      because of chronic epistaxis that had resulted in anemia and weakness. The case
      is presented along with a review of the pertinent literature. The dilemmas
      involved in the clinical decision-making process and treatment of malignancy in
      the elderly patient are discussed. In general, treatment outcomes in cases of
      mucosal melanoma are poor despite combination therapy, and quality-of-life issues
      become as important as attempts at complete extirpation.

PMID- 12239704
TI  - Introduction to this issue: security hospitals: policies, practices, and
      programs.

PMID- 12239705
TI  - Ethics issues in security hospitals.
AB  - The term 'security hospital' is used for a variety of facilities including
      forensic hospitals and prison hospitals, which, because of their mission, the
      nature of their work, and the populations they serve-or because of the authority
      under which they operate-place the staff at considerable risk of ethical
      violations related to either clinical care or to forensic activities. The problem
      of divided loyalties is of special concern in security hospitals. Ethics
      principles particularly at risk are confidentiality and informed consent. Where
      there are cultural disparities between the staff and the patients, differences in
      background, socioeconomic class, education, and other types of diversity,
      cultural awareness is required and must be reflected in appropriate treatment and
      evaluation. To counteract the risks of ethical violations, a security hospital
      should create an ethical climate and develop means to anticipate, prevent, and
      deal with ethical violations. These might include detailed and specific policies
      and procedures, programs of orientation, education, consultation, and liaison as
      well as its own ethics committee.

PMID- 12239706
TI  - Legal issues in maximum security institutions for people with mental illness:
      liberty, security, and administrative discretion.
AB  - This article explores four legal issues relevant to the provision of care in
      secure hospitals. These include the current status of right to treatment
      litigation; the potential impact of the Americans with Disabilities Act; new
      developments in laws governing restraint and seclusion; and the need for uniform
      institutional policies on risk assessment. These issues illustrate the potential
      conflicts between individual autonomy and institutional control that have been at
      the heart of mental health law for three decades. The article suggests that
      because of the diminishing oversight provided by the federal judiciary,
      institutional custodians have a particular obligation to ensure that individual
      rights are not overwhelmed by concerns with security.

PMID- 12239707
TI  - Architectural design of a secure forensic state psychiatric hospital.
AB  - This article describes the architectural design of a secure forensic state
      psychiatric hospital. The project combined input from staff at all levels of the
      client organization, outside consultants, and a team of experienced architects.
      The design team was able to create a design that maximized patient dignity and
      privacy on one hand, and the ability of staff to observe all patient activity on
      the other. The design centers around 24-bed units, broken into smaller living
      wings of eight beds each. Each eight-bed living wing has its own private
      bathrooms (two) and showers (two), as well as a small living area solely reserved
      for these eight patients and their guests. An indoor-outdoor dayroom allows
      patients to go outside whenever they choose, while allowing staff to continue
      observing them. The heart of the facility is a large treatment mall, designed to
      foster the acquisition of social, emotional, cognitive, and behavioral skills
      that will help patients to safely return to their communities.

PMID- 12239708
TI  - Changing a culture: a brief program analysis of a social learning program on a
      maximum-security forensic unit.
AB  - This report presents outcome data collected for a three-year period from a
      maximum-security forensic psychiatric program. Admission and discharge variables,
      restraint/seclusion, and client abuse/neglect data are presented from a one-year
      period that preceded the advent of the Behavior Management Treatment Program's
      (BMTP's) Social Learning Diagnostic Program to two years after implementing the
      Social Learning Diagnostic Program. Significant overall progress and improvement
      was observed in all variables analyzed after instituting a social learning
      program paradigm. This report provides a brief summary of the BMTP's Social
      Learning Diagnostic Program along with a discussion of the role played by
      Dangerousness Management Plans in the treatment of patients within the social
      learning milieu. Additionally the patient population served, and the rationale
      for implementation of a program based in social learning theory, are discussed.

PMID- 12239709
TI  - Effect of a total smoking ban in a maximum security psychiatric hospital.
AB  - An archival study was performed in a maximum security forensic hospital to
      evaluate the effects of a total ban on smoking and all tobacco products. One
      hundred and forty patients were characterized as nonsmokers or light, moderate or
      heavy smokers. Patient records for the four weeks prior to the ban were compared
      with their records for the four weeks subsequent to the ban. Numbers of sick
      calls, total disruptive behaviors and verbal aggression declined markedly and
      significantly following the ban in those patients previously classified as
      moderate or heavy smokers. Weight increased significantly, but almost equally
      regardless of previous smoking status. Patients, and eventually staff, tolerated
      the smoking ban without significant negative effects. Patients relied very little
      on treatment modalities to alleviate nicotine withdrawal. Pre-ban apprehension by
      staff and patients dissipated with time after the smoking ban started.

PMID- 12239710
TI  - Central New York Psychiatric Center: an approach to the treatment of co-occurring
      disorders in the New York State correctional mental health system.
AB  - Central New York Psychiatric Center operates a maximum security inpatient
      treatment hospital and outpatient mental health services for all of the 72 New
      York State prisons. In this article prevalence data, patient characteristics, and
      interventions offered to inmates diagnosed with co-occurring mental illness and
      substance abuse disorders in the New York State prison system are reviewed and
      discussed. Available interventions have resulted from the close collaboration of
      the State Department of Correctional Services and State Office of Mental Health.
      Aspects of current programs and plans for future service developments are
      discussed along with implications for the treatment of an offender population
      diagnosed with a co-occurring disorder.

PMID- 12239711
TI  - Reevaluation of a genetic model for the development of exostosis in hereditary
      multiple exostosis.
AB  - EXT1 and EXT2 are genes that have been shown to cause hereditary multiple
      exostosis (HME), a syndrome marked by the formation of bony growths juxtaposed to
      the growth plate. These genes are members of a growing family of proteins with
      glycosyltransferase activity required for the synthesis of heparan sulfate
      chains. This protein activity is predicted to play a role in the expression of
      proteoglycans on the cell surface and in the extracellular matrix. We and others
      have previously suggested that a two-hit mutational model applies to the
      development of an exostosis where a germline mutation coupled with a somatic
      mutation results in the loss of EXT1 or EXT2 function and subsequent tumor
      formation. We report the direct sequencing and loss of heterozygosity (LOH)
      analysis of 12 exostoses from 10 HME families, 4 solitary exostoses, and their
      corresponding constitutional DNA. Of the 16 exostoses screened, we find only one
      solitary case in which two somatic mutations, a deletion and an LOH, are present.
      This provides limited support for the two-hit hypothesis involving the EXT1 and
      EXT2 genes for the development of an exostosis. Alternative models are developed
      based on the functional significance of EXT proteins in heparan sulfate
      biosynthesis.

PMID- 12239712
TI  - FG syndrome: linkage analysis in two families supporting a new gene localization
      at Xp22.3 [FGS3].
AB  - FG syndrome (OMIM 305450) is an X-linked condition comprising mental retardation,
      congenital hypotonia, constipation or anal malformations, and a distinctive
      appearance with disproportionately large head, tall and broad forehead, cowlicks
      and telecanthus. In a first linkage analysis carried out on 10 families, we
      demonstrated heterogeneity and assigned one gene [FGS1] to region Xq12-q21.31
      [Briault et al., 1997: Am J Med Genet 73:87-90] corroborated by Graham et al.
      [1998: Am J Med Genet 80:145-156]. Heterogeneity was supported by the study of
      one family with apparent FG syndrome co-segregating with an inversion of X
      chromosome [inv(X)(q11q28)] ([FGS2], OMIM 300321) [Briault et al., 1999: Am J Med
      Genet 86:112-114 and Briault et al., 2000: Am J Med Genet 95:178-181]. We present
      the results of a new linkage analysis carried out on two families with FG
      syndrome. The two earlier known loci for FG syndrome, FGS1 and FGS2 (Xq11 or
      Xq28) were excluded by multipoint analysis of both families. Linkage was found,
      however, with locus DXS1060 suggesting that a third FG locus might be located at
      Xp22.3. In this region, two potential candidate genes, VCX-A and PRKX, were
      excluded by sequence analysis of the coding region in patients of the two
      reported FG families. The search for new candidate genes is in progress.

PMID- 12239713
TI  - CFC index for the diagnosis of cardiofaciocutaneous syndrome.
AB  - Controversy exists concerning the delineation of cardiofaciocutaneous syndrome
      (CFC). Many authors have attempted to establish syndrome traits for CFC, but to
      date none are pathognomonic or obligatory. We have created a clinical and
      objective method, called the CFC index, for CFC diagnosis. This method also
      differentiates CFC from Noonan syndrome and Costello syndrome, CFC's main
      differential diagnosis. We propose the use of the CFC index for the confirmation
      of CFC diagnosis and to differentiate CFC from other phenotypically similar
      genetic conditions, while molecular studies are still in progress.

PMID- 12239714
TI  - Family MRX9 revisited: further evidence for locus heterogeneity in MRX.
AB  - Nonspecific X-linked mental retardation (MRX) patients are characterized by
      mental retardation, without additional distinguishing features. Consequently, MRX
      families can only be distinguished by mapping studies; yet, due to imprecise
      mapping studies performed in the past, the number of genes causing MRX is
      debatable, and a more precise localization for families is necessary to estimate
      this number. MRX 9 has been mapped to the pericentromeric region Xp21-q13. We
      refined the mapping of the MRX9 family to Xp11.22-Xp11.4. A sequencing analysis
      of three likely candidate genes in Xp11, SREB3, synapsin I, and TM4SF2, revealed
      no mutations.

PMID- 12239715
TI  - Subtelomeric FISH uncovers trisomy 14q32: lessons for imprinted regions, cryptic
      rearrangements and variant acrocentric short arms.
AB  - The recent development of a set of chromosome-specific, subtelomeric probes has
      proved useful in diagnosis and recurrence risk counseling of patients and
      families with mental retardation and in further characterization of known
      chromosomal abnormalities. Cases of cryptic, subtelomeric rearrangements may
      account for up to 7.5% of cases of idiopathic moderate-severe mental retardation.
      We present the molecular cytogenetic studies of trisomy 14q detected by
      subtelomeric fluorescence in situ hybridization (FISH). Our patient is a 3-year
      old girl with growth and developmental delay, myelomeningocele, partial agenesis
      of the corpus callosum, hypertelorism, tented mouth, simple ears, small mandible,
      and congenital heart disease (atrial and ventricular septal defects with
      subaortic conus). G-banded chromosome analysis was apparently normal. A set of
      FISH-based, subtelomeric, region-specific probes revealed trisomy for 14q in the
      child. Parental FISH studies established that the mother is a balanced carrier
      for a half-cryptic translocation between the distal long arm of chromosome 14 and
      the short arm of chromosome 22. FISH analysis using two BAC clones that contain
      the imprinted genes MEG3 and DLK1, which localize to 14q32, established that our
      patient has two maternal copies of these genes. Because the child does not have
      features of the maternal UPD 14 syndrome, this case suggests that it is absence
      of expression of a paternally expressed gene, rather than overexpression of a
      maternally expressed gene, that is responsible for the maternal UPD 14 phenotype.

PMID- 12239716
TI  - Autosomal recessive alobar holoprosencephaly with essentially normal faces.
AB  - Holoprosencephaly is associated with a diagnostic face approximately 80% of the
      time. We report three siblings with alobar holoprosencephaly and essentially
      normal faces. A similar family was reported by Khan et al. [1970: Dev Med Child
      Neurol 12:71-76]. Alobar holoprosencephaly with essentially normal faces has also
      been observed in infants of diabetic mothers [Barr et al., 1983: J Pediatr
      102:565-568].

PMID- 12239717
TI  - Three novel DNMT3B mutations in Japanese patients with ICF syndrome.
AB  - ICF syndrome is a rare autosomal recessive disorder characterized by
      immunodeficiency, centromeric instability, and facial anomalies. It is caused by
      mutations in a de novo DNA methyltransferase gene, DNMT3B. We here report the
      first three Japanese cases of ICF syndrome from two unrelated families. All
      patients had typical facial dysmorphism and immunoglobulin A (IgA) deficiency,
      but none of them had apparent mental retardation. Cytogenetic analysis of
      peripheral blood lymphocytes showed chromosomal abnormalities, including
      multiradial configurations and a stretching of the pericentromeric
      heterochromatin of chromosomes 1 and 16. Hypomethylation of classical satellite 2
      DNA was also observed. Mutation analyses of DNMT3B revealed three novel
      mutations: patient 1 from the first family was a compound heterozygote for a
      nonsense mutation (Q42Term) and a missense mutation (R832Q); patients 2 and 3
      from the second family were both homozygous for a missense mutation (S282P). The
      R832Q mutation occurred within the conserved methyltransferase domain, and thus
      may affect the enzyme activity directly. The S282P mutation, on the other hand,
      occurred close to the PWWP domain, which is presumably involved in protein
      protein interaction. This is the first missense mutation mapped to the N-terminal
      half of the protein, suggesting that the region plays an important role in the
      regulation of the DNMT3B enzyme.

PMID- 12239718
TI  - Exploring the clinical and epidemiological complexity of GJB2-linked deafness.
AB  - GJB2 mutation analysis was performed in 179 unrelated subjects with sporadic or
      familial hearing loss (HL). Among 57 families, 18 showed a vertical transmission
      of HL, the disease being present in two or three generations. Besides 155
      nonsyndromic cases, 24 patients presenting with extra-auditory clinical signs
      were included in the molecular study. GJB2 mutation analysis was also performed
      in 19 subjects with an anamnestic history of perinatal risks factors for acquired
      HL. The 35delG mutation accounted for 22.1% of analyzed chromosomes in sporadic
      cases and 39.4% in familial cases; 35delG prevalence reached 41% in autosomal
      recessive and 44.4% in pseudodominant pedigrees. Two novel GJB2 mutations were
      identified in compound heterozygosity with 35delG allele (D159V,
      284ins/dup[CACGT]). Two 35delG homozygous subjects were identified among HL cases
      classified as environmental in origin. Four patients 35delG heterozygous
      (35delG/V95M, 35delG/L90P, 35delG/167delT, and 35delG/?) and two homozygous
      presented with extra-auditory clinical signs involving different organs (skin,
      vascular system, hemopoietic lineages, and thyroid). In a high proportion of
      35delG heterozygous HL patients (52%), no second GJB2 mutation was detected. The
      reported data highlight the complexity of the genetic epidemiology of GJB2-linked
      deafness, further enlarging the spectrum of situations in which GJB2 mutation
      analysis should be performed. The presence of extra-auditory signs in a
      significant portion of GJB2-mutated patients suggests the possibility that GJB2
      loss of function could contribute to clinical phenotypes presenting in
      association with deafness. This hypothesis deserves further investigation. The
      failure to identify a presumed partnering GJB2 mutation in a high proportion of
      deaf patients remains a challenging problem to be clarified.

PMID- 12239719
TI  - Idiopathic congenital central hypoventilation syndrome: the next generation.
AB  - Idiopathic congenital central hypoventilation syndrome (CCHS) is a rare disorder
      in which affected children have a decreased sensitivity of their respiratory
      centers to hypercarbia and hypoxia, as well as evidence for generalized autonomic
      nervous system dysfunction. A genetic origin has long been hypothesized for CCHS.
      Previous reports of the syndrome among twins, siblings, and half siblings, as
      well as an established association with Hirschsprung disease and neural crest
      tumors support this genetic hypothesis. Here, we present the first reported
      offspring born to four women diagnosed with idiopathic CCHS. Their children
      display a spectrum of abnormalities with one child being diagnosed with CCHS, one
      child with recurrent apparent life threatening events, one infant born
      prematurely with severe chronic lung disease and diminished ventilatory responses
      to carbon dioxide, and one infant who is apparently healthy with no clinical
      manifestations suggestive of disordered respiratory control to date. Two and
      potentially three of these patients illustrate transmission of altered
      respiratory control by CCHS patients into the next generation, furthering the
      evidence that CCHS is part of a broadly based inherited syndrome of autonomic
      nervous system dysfunction.

PMID- 12239720
TI  - Molecular breakpoint analysis and relevance of variable mosaicism in a woman with
      short stature, primary amenorrhea, unilateral gonadoblastoma, and a
      46,X,del(Y)(q11)/45,X karyotype.
AB  - We report on a 30-year-old woman with short stature, completely female external
      genitalia, primary amenorrhea, bilateral streak gonads, unilateral
      gonadoblastoma, and a 46,X,del(Y)(q11)/45,X karyotype. Variable levels of
      mosaicism were found in blood and cultivated fibroblasts from both the skin and
      ovaries, with the percentage of the 45,X lineage never exceeding 33%.
      Fluorescence in situ hybridization (FISH) was performed with alpha satellite
      centromere region probes of the X and Y chromosomes (DXZ1 and DXZ3) as well as
      with the unique-sequence, locus-specific, sex-determining region of the Y
      chromosome gene (SRY) and the DXZ1 probes. Each signal was noted for DXZ1 on the
      X chromosome and for the Y probes on the marker chromosome. Molecular
      investigations with a panel of PCR markers spread over the whole Y chromosome
      indicated a deletion breakpoint between sY 78 (interval 4) and sY 151 (interval
      5F). No mutation of the high mobility group-box (HMG-box) of the SRY gene could
      be found following sequence analysis. The phenotype/genotype correlation
      demonstrates the broad phenotypic range of low-level 45,X mosaicism with the
      resultant short stature and external female phenotype, despite the presence of
      SRY in a high proportion of cells in various tissues.

PMID- 12239721
TI  - De novo complete trisomy 5p: clinical and neuroradiological findings.
AB  - Partial or complete duplication of 5p is a rare chromosomal abnormality in which
      genotype-phenotype correlation studies are hampered by other commonly associated
      chromosomal abnormalities. We report on a new patient in whom a complete de novo
      trisomy 5p in all metaphases represented the only chromosomal aberration. The
      present case further contributes to delineate the typical clinical picture of the
      trisomy 5p syndrome. Long-term clinical follow-up demonstrated low levels of
      secretory immunoglobulin A (IgA) on several occasions and likely related to the
      patient's recurrent respiratory infections (RRIs), a main clinical feature of the
      trisomy 5p syndrome. An extensive neuroradiological study detected a progressive
      triventricular hydrocephalus during the fist year of life with subsequent
      stabilization. Neuronal migration disorders were also present and probably
      account for the drug-resistant epilepsy presented by the patient.

PMID- 12239723
TI  - Pigmentary mosaicism of the hyperpigmented type in two half-brothers.
AB  - Pigmentary mosaicism is a heterogeneous cutaneous phenotype that is often
      associated with extracutaneous anomalies. It is widely accepted that these
      phenotypes arise de novo as a result of a postzygotic mutation, leading to a
      mosaic status of the embryo. In the vast majority of cases, the occurrence of
      pigmentary mosaicism is sporadic. We report two paternal half-brothers affected
      with pigmentary mosaicism of the hyperpigmented type. The hyperpigmentation in
      both patients is distributed along the lines of Blaschko. In addition, mental
      retardation, facial asymmetry, short stature, scoliosis, and short fingers with
      clinodactyly of the 5th digit were noted in one of them. Chromosome analysis in
      this 15-year-old patient demonstrated a mosaic 46,XY,dup(3)(p21.3;pter)/46,XY
      with 12% aberrant cells in lymphocytes and 2% in skin fibroblasts derived from a
      hyperpigmented area. His nine-year-old half-brother had similar systematized
      hyperpigmented skin lesions, macrocephaly, facial asymmetry, and clinodactyly of
      the 5th digit. Chromosome analysis of peripheral lymphocytes showed a normal
      karyotype 46,XY. A skin biopsy could not be obtained. So far, some familial cases
      of hypopigmentation along the lines of Blaschko have been reported, but familial
      occurrence of the hyperpigmented type of pigmentary mosaicism appears to be
      extremely unusual. It is difficult to establish a causal relationship with the
      chromosomal mosaicism as observed in patient 1. Paradominant transmission seems
      unlikely because this would likewise imply that the chromosomal mosaicism is an
      incidental finding.

PMID- 12239722
TI  - Complex karyotypic abnormality in ovarian fibroma associated with Gorlin
      syndrome.
AB  - Nevoid basal cell carcinoma (NBCC) syndrome is an autosomal dominant disorder
      characterized by distinctive congenital malformations and a variety of benign and
      malignant neoplasms, including ovarian fibromas. We describe pathologic and
      cytogenetic findings in a large unilateral ovarian fibroma from a 12-year-old
      female with NBCC syndrome. The pathologic findings were characteristic for
      ovarian fibroma, but were unusual for the ovarian fibromas associated with NBCC
      syndrome because of the absence of calcification, the lack of bilaterality, and
      the presence of focal hypercellularity. The karyotype of tumor tissue showed
      complex numerical and structural abnormalities. Although there is frequent loss
      of heterozygosity of 9q22.3 and mutations in the PTCHgene in Gorlin syndrome, the
      ovarian fibroma in this case did not have cytogenetically detectable
      abnormalities of chromosome 9.

PMID- 12239724
TI  - Prenatal growth deficiency with narrowness of the cervical spine, subglottic
      stenosis, hip dislocation, and severe delayed bone ossification: a new skeletal
      dysplasia.
AB  - A boy with a severe prenatal onset dysplasia, prominent occiput, hypertelorism,
      epicanthus inversus, low-set ears, flat nasal bridge, small nares, cleft palate,
      subglottic stenosis, narrow cervical canal, undermodeled bones, cortical thinning
      of the diaphyses, hip dislocation, severely delayed bone ossification, and
      apparently normal intellectual development is described. Osseous
      histopathological studies were unremarkable. The boy's parents are first cousins,
      suggesting recessive inheritance. To the best of our knowledge, this association
      has not been reported before, and may be considered a novel syndrome.

PMID- 12239725
TI  - Jagged1 gene mutation for abdominal coarctation of the aorta in Alagille
      syndrome.
AB  - Congenital cardiac defects such as peripheral pulmonary stenosis are well
      described in Alagille syndrome (AGS), which is transmitted in an autosomal
      dominant inheritance. Haploinsufficiency of the Jagged1 (JAG1) gene has been
      shown to cause AGS. Abdominal coarctation is an uncommon vascular congenital
      anomaly which has been described only three times in AGS. Recently, expression of
      the Jagged1 gene has been found in the developing heart and in multiple
      associated vascular structures, including the descending aorta. Mutation analysis
      of the Jagged1 gene in this fourth reported patient with coarctation of the
      abdominal aorta in AGS and right subclavian stenosis identified a mutation
      deletion (1485 Del CT). This agrees with the Jagged1 expression studies and
      suggests that coarctation of aorta may be a component of AGS.

PMID- 12239726
TI  - Osteofibrous dysplasia: two affected male sibs and an unrelated girl with
      bilateral involvement.
AB  - Osteofibrous dysplasia (OFD) is a tumor-like bone lesion that occurs most often
      in the tibia, presenting as a painless swelling or anterior bowing. Radiographs
      show a well-circumscribed intracortical lucency, or multiple lucencies separated
      by sclerotic borders, associated with a diaphyseal expansion. The histogenesis of
      OFD and its possible relationships to fibrous dysplasia and to adamantinoma have
      been the subject of significant discussion and investigation. We have been unable
      to find any reports of familial OFD, and have found only two references to
      bilateral involvement. In this article, we report both bilateral and familial
      involvement, and suggest that more thorough investigation of patients and their
      families may uncover similar cases, and perhaps support a genetic component to
      the etiology of this condition.

PMID- 12239727
TI  - Diploid/tetraploid/t(1;6) mosaicism in a 17-year-old female with hypomelanosis of
      Ito, multiple congenital anomalies, and body asymmetry.
AB  - Many types of chromosome mosaicism have been identified in cases of hypomelanosis
      of Ito, often in association with chromosome instability; however, there have
      been very few cases with diploid-tetraploid mosaicism described in the
      literature. We present a patient with a tetraploid mosaicism: a 17-year-old girl
      who has hypomelanosis of Ito in association with diploid/tetraploid/t(1;6)
      mosaicism. She had multiple congenital anomalies of omphalocele, exstrophy of
      bladder, duodenal web, and imperforate anus. These features have not been
      described previously in diploid-tetraploid mosaicism.

PMID- 12239728
TI  - A second patient with MCA/MR syndrome with multiple circumferential skin creases.
AB  - Symmetrical congenital circumferential skin creases are a rare feature described
      in only a few conditions. We report a case of a 29-month-old boy with symmetrical
      circumferential skin creases on arms, legs, and digits, and other features
      reminiscent of the single case reported by Cohen et al. [1993: Clin Dysmorphol
      2:39-46] and reviewed by Elliott et al. [1996: Am J Med Genet 62:23-25]. The key
      features also include epicanthic folds, microphthalmia, microcornea,
      microcephaly, small, low-set posteriorly angulated ears with thick overfolded
      helices, cleft palate, and moderate-severe psychomotor developmental delay.

PMID- 12239729
TI  - Linear and whorled nevoid hypermelanosis with bilateral giant cerebral aneurysms.
AB  - A 24-year-old woman presented with bilateral giant intracavernous carotid artery
      aneurysms manifesting as a cavernous sinus syndrome on the left side, and
      anisocoria, ophthalmic pain, and oculomotor paresis on the left side. Physical
      examination showed mild hyperextensibility of the metacarpophalangeal joints,
      amelogenesis imperfecta, and hyperpigmentation following Blaschko lines. Analysis
      of the NEMO gene for incontinentia pigmenti syndrome and of collagen III for
      Ehlers-Danlos type IV was normal. Skewed X-inactivation patterns in blood
      lymphocytes were detected. To the best of our knowledge, this association of
      linear hyperpigmentation and cerebral aneurysms has never been previously
      reported.

PMID- 12239730
TI  - Co-occurrence of chromosome 22q11.2 microdeletion and trisomy 21 mosaicism.
AB  - This report describes a patient who had some phenotypic features of Down syndrome
      (DS) as well as severe conotruncal cardiac anomalies, including pulmonary atresia
      with ventricular septal defect (tetralogy of Fallot with pulmonary atresia),
      confluent pulmonary arteries, a large left-sided ductus arteriosus, left aortic
      arch, aberrant right subclavian artery, and secundum atrial septal defect.
      Cytogenetic and fluorescence in situ hybridization (FISH) analysis was carried
      out on peripheral blood lymphocytes and skin fibroblasts using probes specific
      for the chromosomal loci 21q22.13 to 21q22.2 and locus 22q11.2. This revealed
      47,XX+21/46,XX mosaicism at a rate of 15:85 and the micro-deletion 22q11.2
      (del22q11.2). Some patients'congenital cardiac anomalies are atypical for the
      type of mosaicism or aneuploidy. The case suggests that association of del22q11.2
      should be considered in patients with chromosomal mosaicism or aneuploidy who
      also have particular conotruncal cardiac defects.

PMID- 12239731
TI  - Recombinant 4 syndrome due to an unbalanced pericentric inversion of chromosome
      4.
AB  - An informative patient with a MCA/MR syndrome consisting of developmental delay,
      prenatal onset growth delay, microcephaly, distinctive face, iris coloboma, and a
      congenital heart defect was found, on chromosome analysis, to have the following
      complement: 46,XY,rec(4) dup(4p) inv(4)(p14q35.1) mat. He has a partial 4p
      trisomy/distal 4q deletion due to an unbalanced pericentric inversion inherited
      from his mother. Dup (4p) trisomy was originally described by Wilson et al.
      [1970: Am J Hum Genet 22:679-690] in a similar case with the same chromosome 4
      inversion. To date, at least 85 cases of dup (4p) syndrome have been published,
      mostly due to unbalanced translocations. Recent articles suggest that the
      phenotype is hard to recognize clinically due to the lack of specificity of
      findings. In contrast, 4p trisomy due to an unbalanced pericentric inversion of
      chromosome 4(p14q35), i.e., the recombinant 4 syndrome observed in our patient,
      appears to be a discrete entity with relatively consistent features. In total
      there are four other kindreds described in the literature with this inversion,
      and the phenotype seems recognizable. Thus, we suggest that recombinant 4
      syndrome is a discrete entity among 4p trisomy patients.

PMID- 12239732
TI  - Marshall-Smith syndrome in a Taiwanese patient with T-cell immunodeficiency.

PMID- 12239733
TI  - Rubinstein-Taybi syndrome and hypoplastic left heart.

PMID- 12239735
TI  - Congenital Malformations Surveillance Report. A report from the National Birth
      Defects Prevention Network.

PMID- 12239734
TI  - An apparently nonsyndromic infant with the association of anorectal and
      cardiovascular anomalies and a 22q11 deletion.

PMID- 12239736
TI  - Contribution of birth defects to infant mortality in the United States.
AB  - BACKGROUND: While overall infant mortality rates (IMR) have declined over the
      past several decades, birth defects have remained the leading cause of infant
      death in the United States. To illustrate how this leading cause of infant
      mortality impacts subgroups within the US population a descriptive analysis of
      the contribution of birth defects to infant mortality at the national and state
      level was conducted. METHODS: Descriptive analyses of birth defects-specific IMRs
      and proportionate infant mortality due to birth defects were conducted for the US
      using 1999 mortality data from the National Center for Health Statistics. In
      1999, the change to ICD-10 impacted how cause-specific mortality rates were
      coded. Aggregated 1995-1998 state- birth defects infant death statistics were
      used for state comparisons. RESULTS: In 1999, birth defects accounted for nearly
      1 in 5 infant deaths in the US. Variation in birth defects-specific IMRs were
      observed by maternal race with black infants having the highest rates when
      compared with other race groups. However, among black infants prematurity/low
      birthweight was the leading cause of death, followed by birth defects. There is
      substantial variation in state-specific birth defects IMRs and the state-specific
      proportion of infant deaths due to birth defects. CONCLUSIONS: Birth defects
      remain the leading cause of infant death in the United States, despite the
      changes that resulted in 1999 from an update in the coding of cause of death from
      ICD-9 to ICD-10. While birth defects-specific IMRs provide an overall picture of
      fatal birth defects and a gauge of the impact of life-threatening anomalies, they
      represent only a fraction of the impact of birth defects, missing those who
      survive past infancy and those birth defects related losses in the antepartum
      period. Expansion and support of effective birth defects monitoring systems in
      each state that include the full spectrum of perinatal outcomes must be a
      priority. However, paralleling these efforts, analyses of this leading cause of
      infant mortality provide critical insight into perinatal health and should
      continue, with appropriate adjustments for the 1999 classification changes.

PMID- 12239737
TI  - Pregnancy outcome distribution and prenatal diagnosis of autosomal abnormalities,
      Hawaii, 1986-1999.
AB  - BACKGROUND: Approximately 10% of birth defects result from chromosomal
      abnormalities. This study investigated the pregnancy outcome distribution of
      autosomal abnormalities and impact of prenatal diagnosis on autosomal
      abnormalities. METHODS: Data were obtained from a population-based birth defects
      registry and included all autosomal abnormalities delivered in Hawaii during 1986
      1999. RESULTS: There were 1,015 autosomal abnormality cases, consisting of 523
      (52%) live births, 38 (4%) late fetal deaths, 187 (18%) early fetal deaths, 265
      (26%) elective terminations, and 2 unknown pregnancy outcome. Live births
      comprised the majority of translocations (81%), inversions (93%), and deletions
      (84%) but a smaller proportion of trisomies (42%). Autosomal abnormalities were
      prenatally diagnosed in 489 (48%) of the cases, of which 243 (50%) were
      subsequently electively terminated. By type of autosomal abnormality, prenatal
      diagnosis rates were trisomy (44%), translocation (68%), inversion (91%),
      deletion (29%), and subsequent elective termination rates were trisomy (73%),
      translocation (11%), inversion (4%), deletion (50%). The prenatal diagnosis rate
      was higher for maternal age 35 years or greater than for maternal age less than
      35 years (relative risk (RR) 1.8, 95% confidence interval (CI) 1.6-2.0), as was
      the elective termination rate (RR 1.3, 95% CI 1.1-1.6). The prenatal diagnosis
      rate was higher in 1993-1999 than in 1986-1992 (RR 1.2, 95% CI 1.1-1.4), although
      there was no statistically significant difference between the two time periods
      for subsequent elective termination rate (RR 0.9, 95% CI 0.8-1.1). CONCLUSIONS:
      Pregnancy outcome distribution, prenatal diagnosis rates, and subsequent elective
      terminations rates vary by type of autosomal abnormality.

PMID- 12239738
TI  - Descriptive epidemiology of anal atresia in Hawaii, 1986-1999.
AB  - BACKGROUND: Anal atresia is one of the more common birth defects affecting the
      gastrointestinal tract. This study examined the relationship between anal atresia
      and selected demographic and clinical factors in Hawaii. METHODS: Data were
      obtained from a population-based birth defects registry and included all cases of
      anal atresia identified in Hawaii among 1986-1999 deliveries. RESULTS: There were
      124 cases of anal atresia, resulting in a rate of 4.38 per 10,000 live births and
      fetal deaths (95% confidence interval (CI) 3.65-5.23). Cases consisted of 115
      (92.7%) live births, 6 (4.8%) fetal deaths, and 3 (2.4%) elective terminations.
      Chromosomal abnormalities were reported for 10 (8.1%) of the cases, 7 of which
      were trisomy 21. Family history of anal atresia was reported for 3 (2.4%) of the
      cases. No secular trend in anal atresia rates was identified (p=0.617). Risk of
      anal atresia was highest for the 25-29-year maternal age group and lower among
      younger and older maternal age groups. Risk for anal atresia was lower for
      females (relative risk (RR) 0.69 95% CI 0.51-0.91) and higher for live births
      with a birth weight less than 3,000 grams (RR 2.75, 95% CI 2.08-3.56) or less
      than 38 weeks' gestation (RR 3.90, 95% CI 2.88-5.15) and for multiple births (RR
      3.34, 95% CI 1.44-6.57). Anal atresia rates did not vary significantly by
      maternal race/ethnicity, residence at delivery, gravidity, or prenatal care.
      CONCLUSIONS: Anal atresia risk was associated with maternal age, infant/fetus
      sex, birth weight, gestational age, and plurality but not maternal
      race/ethnicity, residence at delivery, gravidity, or prenatal care. Except for
      maternal age, these findings are consistent with the literature.

PMID- 12239739
TI  - Neural tube defect-specific infant mortality in the United States.
AB  - BACKGROUND: Significant resources have been devoted to decreasing the rate of
      neural tube defects (NTDs) in the United States. Both surveillance data and birth
      records have strengths and limitations for evaluating the outcomes of this
      resource allocation. Cause-specific infant mortality data can be used as one
      measure to support evaluation efforts. METHODS: Using period linked birth/infant
      death data from the National Center for Health Statistics (NCHS), a retrospective
      analysis was performed to assess the NTD-specific IMR at the national, state, and
      regional level. NTD-specific IMRs for the United States were calculated from 1996
      to 1998; stratified rates by race/ethnicity, maternal age, age at death, and
      gestational age and birthweight by type of NTD for the total US population were
      based on three-year aggregates (1996-98); state and regional rates were based on
      four-year aggregates (1995-98). RESULTS: Annual US NTD-specific IMRs
      significantly decreased between 1996 and 1998. Black infants were significantly
      less likely to die from an NTD when compared to white infants, largely attributed
      to the high rate of NTD-specific deaths among white Hispanic infants. Infants
      born to women less than 20 years were more likely than infants born to women in
      other age groups to die from an NTD. Seventy-six percent of all NTD-specific
      deaths occurred in the first 23 hours of life. Seventy-four percent of NTD
      specific infant deaths were low birthweight and 58 percent were preterm. The
      Midwest had the highest rate of NTD-specific infant deaths among US regions.
      CONCLUSION: Enhanced prevention efforts are needed to address the disparities in
      infant deaths due to NTDs between Hispanics and other populations, as well as
      women under 20 years. Decreases in NTD-specific IMRs may have been impacted by
      fortification of enriched grain products with folic acid since these efforts were
      optional beginning in 1996. While there are limitations in cause-specific IMRs,
      NTD-specific IMRs can be used as one measure to assess the impact of public
      health interventions aimed at reducing NTDs, respectful of the relatively small
      numbers.

PMID- 12239740
TI  - Decreasing prevalence of neural tube defects in Utah, 1985-2000.
AB  - BACKGROUND: The Utah Birth Defect Network, a statewide surveillance program based
      in the Utah Department of Health, monitors the occurrence of all neural tube
      defects (NTDs). Retrospectively and prospectively population-based data was
      utilized to assess the trend in prevalence for NTDs in Utah from 1985-2000.
      METHODS: The Utah Birth Defect Network (UBDN) has prospectively identified NTDs
      in Utah since 1994. NTD cases, including meningomyelocele, meningocele,
      anencephaly (including exencephaly), encephalocele and craniorachischisis, born
      to women who are residents of Utah at delivery are reviewed by a pediatric
      geneticist. All NTDs occurring from 1985-1993 were ascertained retrospectively
      and documented to be a case. NTDs from all pregnancy outcomes are included (live
      births, stillbirths and pregnancy terminations) during the entire study period.
      RESULTS: NTDs in Utah have decreased significantly between 1985-2000 and remain
      at the lowest prevalence over the last three of those years. The most significant
      decrease was seen from 1993-2000. The downward trend was demonstrable for
      anencephaly and meningomyelocele but not for encephalocele. The proportion of
      NTDs diagnosed prenatally, as well as those pregnancies terminated after prenatal
      diagnosis have remained constant, without any evidence of an increasing trend
      since 1990. However, the proportion of pregnancy terminations occurring prior to
      twenty weeks gestation has increased significantly since 1990. CONCLUSIONS: The
      reason for the observed decrease is not known but is likely the result of
      simultaneous prevention activities locally and nationally, the Utah population's
      propensity for vitamin and supplement consumption, and recent food fortification.
      The Centers for Disease Control and Prevention recommended in 1992 that all women
      in their childbearing years take folic acid daily. The Utah Folic Acid
      Educational Campaign targeted all women of childbearing years beginning in 1996
      with this message. Additionally, fortification of grains was voluntary from 1996,
      became mandatory in 1998 at which point NTD prevalence declined to its lowest
      level. These factors may have collectively contributed to the reduction observed
      in NTD prevalence within Utah, demonstrating the positive impact of an important
      public health endeavor.

PMID- 12239742
TI  - Impact of including elective pregnancy terminations before 20 weeks gestation on
      birth defect rates.
AB  - BACKGROUND: The majority of U.S. birth defects surveillance programs do not
      include elective terminations before 20 weeks gestation among the pregnancy
      outcomes covered. To assess the impact of defects among elective terminations
      before 20 weeks gestation, data from a birth defects registry that does include
      terminations before 20 weeks gestation were analyzed. METHODS: Using information
      from the Texas Birth Defects Registry, the number of cases and rate of 49
      conditions were analyzed in two ways: excluding defects detected among elective
      pregnancy terminations before 20 weeks gestation, and including defects among
      terminations before 20 weeks. RESULTS: By including defects detected among
      elective terminations before 20 weeks, the number of cases increased by five
      percent or greater for nine conditions: anencephaly (29%); spina bifida without
      anencephaly (13%); encephalocele (21%); Patau syndrome (19%); Edwards syndrome
      (11%); Down syndrome (6%); omphalocele (15%); gastroschisis (5%); and
      anophthalmia (7%). There was no impact for 27 conditions, for which there were no
      cases detected among elective terminations before 20 weeks. The greatest impact
      was observed for anencephaly; the rate of anencephaly increased from 2.76 to 3.56
      per 10,000 live births when defects among elective terminations before 20 weeks
      were included. CONCLUSIONS: Excluding defects among elective terminations before
      20 weeks results in counts and rates that are somewhat incomplete, especially for
      conditions that are more commonly detected and electively terminated before 20
      weeks. The impact varies by condition.

PMID- 12239741
TI  - Knowledge, use, and education regarding folic acid supplementation: continuation
      study of women in Colorado who had a pregnancy affected by a neural tube defect.
AB  - BACKGROUND: This study was conducted to: (1) determine whether women who have had
      a neural tube defect (NTD) affected pregnancy know about recommendations for NTD
      recurrence prevention; (2) educate them about the recommendations; and (3) ensure
      that they have access to folic acid prior to another pregnancy. METHODS: Colorado
      women who had an NTD affected pregnancy in 1999 or later were interviewed about
      their knowledge and use of folic acid, provided with verbal information about
      folic acid and NTD prevention, and offered written information and a voucher for
      free folic acid. RESULTS: Thirty-two of 68 women who had an NTD affected
      pregnancy were interviewed. Of these, 22 (69%) were aware of the 0.4 mg. folic
      acid recommendation for women of child bearing age who have not had an NTD
      affected pregnancy (MMWR, '91). Only 15 (47%) of the women knew about the U.S.
      Public Health Service recommendation (MMWR, '92) to consume 4.0 mg of folic acid
      prior to another pregnancy for NTD recurrence prevention. Twenty-five (78%) of
      the women reported taking a multivitamin or folic acid daily. CONCLUSIONS: Nine
      years after national folic acid recommendations, a majority of interviewed women
      (53%) with NTD affected pregnancies did not know about the recommendation to
      consume 4.0 mg of folic acid for NTD recurrence prevention. This sample of women
      are receptive to information about folic acid. Health care providers and public
      health officials should ensure that education about folic acid is provided in an
      effective and timely manner to women with NTD-affected pregnancies.

PMID- 12239743
TI  - Regional bias in birth defect prevalence rates for Arkansas: influence of
      incomplete ascertainment along surveillance system borders.
AB  - BACKGROUND: As part of the continuing evaluation of the Arkansas Reproductive
      Health Monitoring System (ARHMS), we assessed the effects on birth defect
      prevalence rates introduced by incomplete case ascertainment along surveillance
      boundaries. METHODS: Using data from ARHMS and Arkansas Vital Statistics for 1993
      1998, we determined birth defect prevalence rates (per 10,000 live births),
      stratified by race, among three geographic comparison groups of counties. These
      included: (1) the Northeast Group, near the state border at Memphis, Tennessee;
      (2) the Central Group, surrounding Little Rock, Arkansas; and (3) the Southwest
      Group, near Texarkana, Texas. These counties have similar socioeconomic measures
      and proximity to health care facilities, but are differentiated by limitations
      imposed by ARHMS' surveillance borders. Maternal age-standardized rates from the
      control groups were used to impute expected rates, for the Northeast Group and
      statewide, which were compared with reported rates. RESULTS: We found that there
      were 620 fewer reported birth defect cases than expected for the Northeast Group.
      The Northeast Group's prevalence rates were approximately half of the control
      groups' rates (310.6 vs. 529.8, respectively, for Whites, and 240.8 vs. 550.1,
      respectively, for African-Americans). Incorporating the missed cases into
      statewide prevalence calculations could increase prevalence rates from 502.6 to
      523.2 for Whites and from 527.4 to 590.7 for African-Americans. CONCLUSIONS: This
      study identified significant regional differences in reported birth defect rates
      in Arkansas. Case ascertainment might be incomplete in other surveillance systems
      lacking the means to share data with neighboring systems. Regional inaccuracy can
      hinder evaluation of localized birth defect trends or targeted prevention
      efforts.

PMID- 12239744
TI  - A multiple source methodology for the surveillance of fetal alcohol syndrome--The
      Fetal Alcohol Syndrome Surveillance Network (FASSNet).

PMID- 12239745
TI  - Methods for a public health response to birth defects clusters.
AB  - Few resources are available to guide public health officials in investigations of
      reported birth defects clusters. The majority of published resources focus on the
      investigation of cancer and infectious disease clusters and do not address
      clinical and epidemiologic concerns specific to birth defects research. This
      document aims to address these concerns, discuss the needs of the affected
      community, and provide suggestions for the development of a standardized protocol
      to be used as a guide in the investigation of birth defects clusters. We suggest
      that health departments and birth defects registries that may receive reports of
      birth defects clusters establish a protocol for responding that includes the
      following steps: develop a proactive plan for future birth defects cluster
      reports (step I), receive report of a birth defects cluster (step II), verify
      diagnoses and complete case ascertainment (step III), compare the observed rate
      to a reference rate (step IV), ascertain exposures among cases from available
      records (step V), interview case mothers (step VI), initiate further
      epidemiologic study-selection of controls (step VII), and communicate results to
      the community (step VIII). Specific criteria for continuing or terminating an
      investigation should be established before receiving cluster reports. The
      recommendations in this report should be carefully considered to ensure that the
      specific needs of the region, agency and affected community are met.

PMID- 12239746
TI  - State birth defects surveillance programs directory.

PMID- 12239747
TI  - Birth defects surveillance data from selected states, 1995-1999.

PMID- 12239748
TI  - Neural tube defects (NTDs) rates, 1995-1999.

PMID- 12239749
TI  - Appendix A: ICD-9 and CDC/BPA codes.

PMID- 12239750
TI  - The oestrogen-progesterone receptor ratio: an indicator of breast cancer
      evolution.
AB  - Two groups of patients were chosen from among 4,025 subjects examined in a breast
      screening program, one consisting of patients with stage I and the other of
      patients with stage IV breast cancer, characterized by neoplastic recurrence. In
      this comparison p53, HER and grading are of no direct help. We investigated
      receptor status at the time of the first operation and after complete surgical
      excision of the recurrence. The following variables were determined: oestrogen
      and progesterone receptor measures (ER, PR) in f.mol/ml, the 4 receptor
      phenotypes, the oestrogen-progesterone ratio and histological tumour grading in
      relation to oestrogen receptor positivity or negativity. Surgery consisted in
      quadrantectomy or total mastectomy, with axillary dissection or complete surgical
      excision of the recurrence. Adjuvant therapy was administered. The results show a
      different receptor percentage in recurrence compared to early breast cancer,
      which though not significant, indicates a reduced presence of ER+ PR+, ER- PR-,
      and an increase in the ER+PR- phenotype. Recurrence occurs more frequently when
      the lesion at the first operation is more advanced and if radiotherapy has not
      been included in the treatment. Histological grading shows a greater number of
      undifferentiated cells and a reduction in ER+ in recurrence, thus indicating a
      reduced target for the most widely used hormone treatments. The oestrogen
      progesterone ratio is significantly increased (P < 0.01) in recurrence compared
      to stage I cancers. The cause of recurrence is a neoplastic embolism, often
      documented histologically. Recurrence does not necessarily mean a poor prognosis,
      because there is a survival rate after two years of 77% of the cases treated.
      These results obtained with widely used methods show the aggressiveness of some
      breast tumours, which can evolve and have a very poor prognosis even with the
      most complete therapy.

PMID- 12239751
TI  - Advantages and disadvantages of enteric versus bladder diversion in simultaneous
      kidney-pancreas transplantation.
AB  - Simultaneous kidney-pancreas transplantation is universally accepted as being the
      first-choice treatment for insulin-dependent diabetes mellitus in young patients
      with end stage renal disease. One hundred and fifty-six simultaneous kidney
      pancreas transplantations were evaluated, namely, 33 segmental pancreas
      transplants with duct occlusion using neoprene (group I), 73 whole pancreas
      transplants with bladder diversion (group II) and 46 whole pancreas transplants
      with enteric diversion (group III) (37 with systemic venous drainage and 9 with
      portal diversion). Patient actuarial survival rates at 1, 5 and 10 years were
      85%, 78% and 49%, respectively, in group I and 95%, 78% and 65% in group II. In
      group III the rates were 87% and 72% at 1 and 3 years, respectively. Kidney
      survival rates at 1, 5 and 10 years were 83%, 72% and 36% in group I and 89%, 78%
      and 59% in group II. In group III the survival rates were 85% and 72% at 1 and 3
      years. Pancreas survival rates at 1, 5 and 10 years were 66%, 37% and 15% in
      group I and 73%, 67% and 65% in group II. In group III the rates were 87% and 68%
      at 1 and 3 years. Developments in the fields of organ retrieval technology,
      clinical immunosuppression and surgical technique have enabled us to improve our
      success rates, both in terms of organ survival and the quality of life of kidney
      pancreas transplant recipients.

PMID- 12239752
TI  - [Evaluation of surgical risk in elderly patients: a review of 207 cases].
AB  - Thorough evaluation of surgical risk represents the sine qua non for a correct
      therapeutic choice particularly in the elderly who are frequently affected by
      multiple pathologies. The aim of this study was to evaluate the prognostic value
      of two of the most common classification systems for predicting surgical risk
      (ASA and Reiss scores) and of other laboratory parameters. A consecutive series
      of 207 patients aged 70 or above were analysed retrospectively, considering age,
      ASA and Reiss scores, elective or emergency surgery, operative time, leucocytes,
      haemoglobin, creatinine, and albumin levels. Morbidity and mortality rates were
      compared in relation to these parameters. Emergency surgery was associated with
      significantly higher morbidity (P = 0.006 chi-square) and mortality (P = 0.001
      chi-square) than elective surgery. No differences in morbidity were noted in
      association with the ASA classification (P = 0.07 chi-square), though there was a
      significant difference (P = 0.001 chi-square) in mortality. Significant
      differences in both morbidity (P = 0.04 chi-square) and mortality (P = 0.001 chi
      square) were found to be associated with the Reiss classification. Multivariate
      analysis showed that ASA score (P = 0.006), Reiss score (P = 0.004), operative
      time (P = 0.005), and haemoglobin level (P = 0.01) were independent prognostic
      factors. The results of the study confirm the prognostic value of multiparametric
      classifications such as the ASA and Reiss score in elderly patients, even if the
      addition of other prognostic factors may be expected to improve the sensitivity.

PMID- 12239753
TI  - [Control of aerostasis in pulmonary metastasectomy by precision resection.
      Standard technique versus fibrin glue modification].
AB  - The control of aerostasis after performing non-anatomical pulmonary resections
      constitutes a serious problem. The presence of an air leak in the postoperative
      period requires a prolonged thoracic drainage and consequently a longer hospital
      stay. The aim of our study was to evaluate the usefulness of fibrin glue and its
      effectiveness in the prevention of air leaks. At the Department of Thoracic
      Surgery of the National Cancer Institute of Milan, we conducted a case-control
      study in 90 patients submitted to metastasectomy for secondary lung cancer,
      removing multiple small nodules < or = 1.5 cm using the precision resection
      technique. We divided the patients into two groups, both of 45 subjects: group 1
      treated with fibrin glue and group 2 submitted to cauterization of the pulmonary
      parenchyma. The patient characteristics were well matched for age, type of
      approach and operation, number of resections performed and type of pathology. The
      assessment parameters investigated were the duration of the air leak, expected
      complications, drainage time and length of hospital stay. In group 1 we performed
      fewer than 5 precision resections in 21 cases, from 5 to 10 in 16, and more than
      10 in 8. In group 2 we executed fewer than precision resections in 21 cases, from
      5 to 10 in 17, and more than 10 in 7. In group 1 the duration of the air leak was
      2.93 +/- 1.91 days as against 6.95 +/- 7.01 days in group 2 (p = 0.000). In group
      1 we had one complication (2%) (a long-term air leak lasting > 10 days), while in
      group 2 we had a long-term air leak in 11 cases (24%) (p = 0.000). Mean thoracic
      drainage time was 4.22 +/- 1.43 days in group 1, and 8.13 +/- 7.37 in group 2 (p
      = 0.000). The mean postoperative hospital stay was 6.22 +/- 1.43 days in group 1
      compared to 10.13 +/- 7.37 days in group 2 (p = 0.000). In the group of patients
      treated with fibrin glue we obtained a significant reduction in drainage time,
      complications and postoperative hospital stay. The results of our experience show
      that the use of fibrin glue in non-anatomical resections with a high risk of
      developing air leakage is effective in reducing the expected complications, with
      a favourable impact also on the quality of life of patients with metasases.

PMID- 12239754
TI  - [Treatment of pancreatic necrosis and secondary pancreatic infections].
AB  - Acute pancreatitis is a disease capable of the widest clinical expression,
      ranging from mild discomfort to multiorgan failure and death. Moreover, the
      process may remain localized in the pancreas, or spread to regional tissues, or
      even involve remote organs. Despite several efforts, the pathophysiology of acute
      pancreatitis and its complications remains obscure. In the absence of an
      understanding of the pathogenesis and the reasons for the variations in severity,
      the study and management of acute pancreatitis has necessarily been empirical.
      There is little doubt that the development of pancreatic necrosis in patients
      with acute pancreatitis results in an increase in clinical severity and an
      escalation of the mortality risk when compared to interstitial pancreatitis.
      Furthermore, the mortality risk of patients with sterile pancreatic necrosis is
      markedly different from that of patients developing secondary infections in pre
      existing pancreatic necrosis. Infected pancreatic necrosis is uniformly fatal, if
      untreated. While most authorities agree that surgical debridement is required for
      survival in patients with secondary pancreatic infections, the precise form of
      the subsequent drainage has become a matter of some controversy. In this paper we
      discuss the most recent insights relating to the nosographical classification of
      pancreatic necrosis and secondary pancreatic infections, along with an analysis
      of the findings in the literature regarding the surgical treatment of these
      conditions.

PMID- 12239756
TI  - [Therapy of post-necrotic pancreatic pseudocysts: invasive treatments and their
      results].
AB  - Pancreatic pseudocysts are the most common lesions of the pancreas. Endoscopic
      and US-endoscopic techniques are today the best minimally invasive diagnostic and
      therapeutic procedures available for this pathology. From January 1980 to
      December 2001 we observed a total of 74 patients with pancreatic pseudocysts
      secondary to acute pancreatitis. Twelve patients were treated by medical therapy,
      37 with a surgical approach, 15 by endoscopic drainage and 10 by CT-guided
      drainage. The mean size of the pseudocysts was 12.9 cm (range: 3.4 to 24 cm) and
      69.4% were larger than 10 cm. CT-guided drainage had a 50% complication rate (P =
      0.00814), a 20% mortality rate (P = 0.00463) and a 10% relapse rate. The surgical
      approach was associated with a complication rate of 18.9% and a 5.4% relapse
      rate. The endoscopic approach presented a 13% morbidity rate and a 6.6% relapse
      rate. CT-guided drainage is the therapeutic approach we use in emergency cases,
      but endoscopic therapeutic technique is the best procedure and is a valid
      alternative to surgical and CT-guided drainage. The shortest mean hospital stay
      (4.8 days) was observed with the endoscopic approach.

PMID- 12239755
TI  - [Prognostic importance of preoperative CEA in patients with colorectal cancer].
AB  - Carcinoembryonic antigen is an acid glycoprotein, the levels of which may
      increase in patients with colorectal carcinoma. The prognostic significance of
      preoperative carcinoembryonic antigen levels and their relationship to other risk
      factors are still debatable issues. Among 512 patients operated on for colorectal
      cancer, whose preoperative carcinoembryonic antigen concentrations were
      evaluated, linear correlations were established between carcinoembryonic antigen
      overexpression and carcinoma staging, diameter and grading, though these were not
      statistically significant. Moreover, metastatic cancers were significantly more
      frequent in patients with increased plasma concentrations of the marker (> 60
      ng/ml). There were no correlations between increased carcinoembryonic antigen
      levels and age, ploidy, or site and shape of the cancers. As regards survival,
      patients with normal preoperative carcinoembryonic antigen levels had a better
      prognosis in terms both of lower local recurrence rates and long- term survival.
      In addition. In Dukes stages B and C elevation of carcinoembryonic antigen above
      the cut-off point can be considered a significant prognostic factor capable of
      identifying a group of patients at high risk who may be candidates for aggressive
      adjuvant therapies and follow-up. The findings of this study suggest that
      preoperative carcinoembryonic antigen levels are of prognostic importance in
      relation both to cancer staging and to long-term survival, which may have
      significant clinical applications.

PMID- 12239757
TI  - [Reoperation on the femoral arterial bifurcation: technical notes and surgical
      strategy].
AB  - Femoral bifurcation reoperation is a stern test for skilfull surgeons, owing to
      the presence of thick scar tissue from the previous operations, especially when
      prosthetic grafts are used. In cases of aorto-femoral graft thrombosis, if
      thrombectomy of the entire graft is possible, one could isolate the anastomotic
      tract with all the afferent vessels and construct a new anastomosis downstream in
      tissue which allows a better run-off. Often in our experience we executed a by
      pass, with a vein or short tract of new graft, from the previous prosthetic
      branch to a distal part of the deep femoral artery. In this way the reoperation
      is faster and safer, limiting dangerous dissection times. In infected inguinal
      pseudo-aneurysms we prefer an axillo-femoral by-pass, with isolation of the deep
      femoral artery by lateral incision, outside the infected field. In the non
      infected ones, the reconstruction involves the use of a new small-sized graft
      between the previous structures. In cases of femoro-femoral occlusion we think it
      is better, first of all, to evaluate the possibility of an orthotopic graft from
      the aorta or iliac artery.

PMID- 12239758
TI  - Prospective randomised study of cephalic vein cut-down versus subclavian vein
      puncture technique in the implantation of subcutaneous venous access devices.
AB  - The aim of the present study was to evaluate the results of a prospective
      randomised trial comparing cephalic vein cut-down (CCD) versus percutaneous
      subclavian vein puncture with the Seldinger technique (PSP) in the implantation
      of subcutaneous permanent central venous access devices (SPCVAD) in order to
      better define the safer technique in outpatient surgery. Fifty patients were
      randomly divided into two groups: CCD--17 males, 8 females (age range: 35-75
      years; mean: 60 years); PSP--17 males, 8 females (age range: 17-75 years; mean:
      63 years). The two groups were compared in terms of implant morbidity, technical
      failure, operative time, patient acceptance, and healthcare costs. Data were
      analysed statistically using the chi-square test (P < 0.05 was considered
      significant) and Student's t-test. Technical failure occurred in 2 PSP patients
      (8%) and in 4 CCD patients (16%) (P = 0.663; chi 2 = 0.189). Mean operative time
      was 40 min in PSP (range: 35-70 min) and 50 in CCD (range: 35-60 min) (p = 0.108,
      T = -1.64). Patients were requested to define the pain experiences as a result of
      the operation as mild, moderate or severe: 23 PSP patients reported mild to
      moderate pain (92% of cases), and 2 patients severe pain (8%). The same figures
      were obtained in the CCD group, i.e. 23 (92%) and 2 (8%) patients, respectively
      (P = 0.377; chi 2 = 0.781). In our institute both types of implant cost $1260; in
      the case of PSP there is an additional cost of $120 for postoperative chest x
      rays, making a total cost of $1380 per implant. The data of this randomised trial
      show that the implantation of a totally implantable vascular access device is a
      surgical procedure with a limited rate of morbidity in both cephalic vein cut
      down and subclavian vein percutaneous puncture, with no statistically significant
      difference between the two in terms of associated morbidity, technical failure,
      operative time and patient acceptance.

PMID- 12239759
TI  - [Voluntary or accidental ingestion of foreign bodies: clinical considerations in
      142 cases].
AB  - The authors report on a series of 142 patients who had swallowed foreign bodies
      over the period 1981-1999. After outlining the various ways in which the foreign
      bodies were swallowed and the fact that they were eliminated spontaneously by
      natural routes in 80-90% of cases, the authors deal at some length with the
      serious complications that occurred in some of these cases, which, as a result of
      their characteristics and mode of ingestion, may require emergency surgery for
      their resolution. In particular, the authors describe 6 cases of foreign bodies
      that were urgently removed by endoscopy and also describe 3 cases in detail (1
      perforation and 2 bowel obstructions) in which a laparotomy was required not only
      to correct the complication but also to definitively clarify the diagnosis.

PMID- 12239760
TI  - Bile leak from the hepatic bed after laparoscopic cholecystectomy.
AB  - The aim of our study was to identify the best treatment for bile leakage from the
      gallbladder or hepatic bed as a result of laparoscopic cholecystectomy. Two
      hundred and fifty laparoscopic cholecystectomies were performed in our department
      from January 1997 to January 1999 and bile leak was identified in 5 cases (2%).
      In one case, a right subphrenic collection was detected and resolved with a
      percutaneous drainage. At ERCP all cases showed a small leak from an accessory
      hepatic duct (2 pts.) or from the hepatic bed (3 pts.), successfully managed with
      an immediate endoscopic sphincterotomy, with placement of a nasobiliary tube or a
      biliary endoprosthesis. The incidence of leakage from an accessory hepatic or
      from Luschka's duct is not well known. This complication can be successfully
      managed with endoscopic treatment.

PMID- 12239761
TI  - [Acute abdominal complications in bone marrow transplant recipients].
AB  - Bone marrow transplant is currently the treatment of choice for a number of
      haematological neoplasms. High doses of antiblastic drugs, immunosuppressive
      agents and acute graft versus host disease before and after bone marrow
      transplant cause toxic damage to the liver and to the gastrointestinal tract.
      Related acute abdominal complications often need emergency surgical treatment
      with a 30-60% mortality rate. In these patients the surgical strategy is complex
      and hard to schematise. Ninety-one patients undergoing bone marrow
      transplantation showed acute abdominal symptoms requiring thorough surgical
      monitoring: 51 had ileocolitis, 17 pancreatitis, 9 cholangitis, 6 cholecystitis,
      6 appendicitis, and 2 gastric perforation. Nine patients needed an emergency
      operation (2 gastroduodenal resections, 1 ileal resection, 2 right
      hemicolectomies, 2 total colectomies, 1 cholecystectomy and one appendectomy. The
      operative mortality was 22.2%. Positive blood cultures were quite frequent
      (63.7%). Moderate granulocytopenia was observed (neutrophils: 500 x mm3) in about
      40% of cases, and severe granuloctopenia in only one patient (neutrophils: 100 x
      mm3) with ileotyphlitis. Moderate thrombocytopenia (PLTS < 50,000 x mm3) was
      observed in 43.9% of cases while in three cases (all submitted to surgical
      treatment) the platelet count was < 5,000 x mm3. The recent increase in bone
      marrow transplants has led to a progressive rise in the number of patients with
      acute abdominal complications. When deciding the surgical strategy in treating
      acute abdominal complications the surgeon must consider that surgical
      intervention is indicated only after unsuccessful medical treatment and that the
      intestinal segment involved must always be removed as far as possible; severe
      neutropenia, thrombocytopenia (< 10,000 x mm3) and positive blood cultures,
      especially for CMV, are unfavourable prognostic factors.

PMID- 12239762
TI  - [Splenic abscesses: 6 cases in 15 years].
AB  - Splenic abscesses are a rare type of disease, owing to the quite exceptional
      primary forms, but the prevalence of the disease is rising as a result of the
      increase in the population at risk. The authors report on their experience based
      on 6 observations of such cases over a period of 15 years. The diagnosis was
      obtained by ultrasonography in all 6 cases. Only one case was successfully
      treated by percutaneous drainage, the other 5 all requiring splenectomy. Only one
      patient, suffering from Chediak-Higashi disease, died of bronchopneumonia 6
      months postoperatively. Nowadays the disease is diagnosed earlier than it was in
      the past owing to the increasingly widespread use and refinement of diagnostic
      methods, but even today identification of splenic abscess may still be late due
      to the presence of predisposing diseases which mask the clinical picture, and
      also because, since the condition is so rare, one very often fails to think of it
      in the early stages. An analysis of the recent literature indicates that
      percutaneous drainage is a reliable technique which presents a high therapeutic
      success rate and low cost compared to surgery. Though we believe that the ongoing
      progress in the fields of ultrasonography and CT-guided intervention may allow us
      to treat increasing numbers of patients with splenic abscesses in future, we
      feel, also in the light of our own experience, that splenectomy still remains the
      reference treatment, in that ideal conditions for successful percutaneous
      drainage do not often present themselves.

PMID- 12239763
TI  - [Use of prostheses in the treatment of laparocele].
AB  - Effective solutions to the problem of surgery for bulk laparoceles began to
      emerge with the introduction of synthesis materials that can be used to reinforce
      or replace the abdominal wall. The ideal prosthesis has yet to be found, though
      today a large number of laparoceles are treated with the use of polypropylene
      (Marlex) and PTFE (Goretex), which are considered the best materials for
      alloplasty with only a very limited number of recurrences and complications. The
      authors describe their experience over two distinct periods: in the first of
      these, from 1985 to 1994, 49 of 126 patients were treated with prostheses (39
      using the Rives technique and 10 simple alloplasty); in the second period, from
      1995 to 2000, 39 of 79 patients were treated with prostheses (12 using the Rives
      technique and 27 simple alloplasty). This prosthesis was used only to reinforce
      the abdominal wall with a modified technique. The mortality rate was nil. In the
      first period the complications presented by the 49 patients were 6 seromas and 3
      infections; in the second period (39 patients) the complications observed were 3
      seromas, resolved with conservative therapy, and one relapse due to the use of a
      Vycril prosthesis. One case of haematoma and one of subcuticular infection
      occurred, but neither of these required removal of the prosthesis.

PMID- 12239764
TI  - [Laparoscopic treatment of benign ovarian cysts].
AB  - Laparoscopic surgery is the most frequent indication for the management of benign
      ovarian cysts in the obstetric and gynaecological field. On the basis of their
      experience the authors address the clinical classification of benign ovarian
      pathology and the surgical laparoscopic procedures utilised in the treatment of
      adnexal cysts. Forty-two patients underwent laparoscopic surgery after a
      preoperative clinical and biological evaluation and imaging in order to exclude
      the presence of ovarian malignancies. All surgical procedures were carried out
      laparoscopically, with a conversion index of 0%. The morbidity was 2.3% (one case
      of haematoma of the umbilical trocar site) and there was no mortality. No late
      complications were observed. In conclusion, laparoscopic surgery in the
      management of ovarian cysts is technically feasible. On the basis of these
      findings laparoscopic surgery is the treatment of choice for adnexal cystic
      tumours after careful exclusion of malignancy.

PMID- 12239765
TI  - [Carcinoma of the pancreatic remnant developing after pancreaticoduodenectomy for
      adenocarcinoma of the head of pancreas].
AB  - In November 1996 a 44-year-old man with an adenocarcinoma of the pancreatic head
      (T2 N1 Mx- UICC 1998 Stage III) underwent a Traverso-Longmire
      pancreaticoduodenectomy. Early reoperation was required owing to postoperative
      acute pancreatitis and haemorrhage of the pancreatic remnant, after which he
      received chemo- and radiotherapy. Twenty-nine months later, an increase in the
      level of CA19.9 was observed with neither clinical nor radiological evidence of
      cancer recurrence. Forty months later, there was evidence of a new neoplasia of
      the pancreatic remnant. Since the recurrence involved only the pancreatic remnant
      with no evidence of metastases and the patient was in good condition and enough
      time had elapsed since surgical eradication of the primary cancer, we decided to
      perform an en bloc resection of the pancreatic body and tail and the spleen.
      Histologically, the tumour proved to be a pancreatic adenocarcinoma (T2). It is
      difficult to assess whether this cancer of the pancreatic remnant was a
      recurrence or a second primary cancer because of the long recurrence-free
      survival period, the absence of neoplastic invasion of the resection margins of
      the two surgical specimens and the absence of multicentricity both of the portion
      of the gland removed by the first operation and that removed by the second.

PMID- 12239766
TI  - Retrorectal tumours: a case report.
AB  - The authors describe a case of retrorectal tumour in a 48-year-old female.
      Retrorectal tumours are rare, and their diagnosis is notoriously difficult and
      late. In this case the first-step diagnosis was made on the basis of clinical
      findings and radiological investigations such as abdominal ultrasonography. The
      second step included pelvic CT scans and MR imaging which yielded more precise
      anatomical details and information for the best surgical approach. We opted for a
      posterior approach with complete, easy removal of the tumour mass which, after
      pathological examination, turned out to be an epidermoid cyst. The postoperative
      course was uneventful and, one year after operation, the patient complains only
      of mild, irregular perineal pain with completely negative radiological
      investigations (US and CT scan).

PMID- 12239767
TI  - [Primary lymphoma of the rectum: a case report and review of the literature].
AB  - A case of primary malignant lymphoma of the rectum is presented and the
      literature reviewed. The authors recommend a complete diagnostic evaluation to
      assess the unifocal nature of the tumour and stage it, as well as in order to
      exclude systemic disease. Surgical therapy combined with chemo- and radiotherapy
      is the best choice when the disease is confined to the rectum, with a better
      prognosis than those cases treated by chemo- and radiotherapy alone. Because of
      the extreme rarity of the disease it is impossible to find randomised studies and
      any evaluation of prognosis can only be done on the basis of the small case
      series reported in the literature.

PMID- 12239768
TI  - Small bowel necrosis associated with postoperative enteral feeding.
AB  - Enteral feeding by jejunostomy is one of the main surgical procedures used to
      supply the proteins and calories necessary in the early postoperative period
      after major surgery of the upper digestive tract. The complications associated
      with early postoperative enteral feeding may vary from signs of gastrointestinal
      intolerance such as nausea, emesis, diarrhoea and cramp-like abdominal pain to
      hypotension and hypovolaemic shock, and also to the development of small bowel
      ischaemia and necrosis. Ischaemic intestinal involvement with progression towards
      necrosis is fortunately a rare event. The cause is not well known. A
      multifactorial pathogenesis of the mucosal damage has been proposed, where
      hyperosmolarity of feeding and bacterial overgrowth, due to excessive
      fermentation of carbohydrates, a decreased mesenteric blood flow and a lowering
      of peristalsis have been adduced as causes of mucosal injury. We report a case of
      intestinal necrosis following a jejunostomy procedure, which led to ileal
      resection.

PMID- 12239769
TI  - Poorly differentiated jejunal adenocarcinoma in a patient with coeliac disease: a
      case report.
AB  - It is well known that coeliac disease increases the risk of gastrointestinal
      lymphomas, whereas adenocarcinoma is a rare complication. The authors report a
      case of a poorly differentiated jejunal adenocarcinoma complicating coeliac
      disease in a 40-year-old female and discuss the clinical, diagnostic and
      therapeutic aspects.

PMID- 12239770
TI  - [Acute abdomen due to a strangulated and perforated para-esophageal hernia. A
      case report].
AB  - Para-oesophageal hiatus hernia, a condition in which the fundus and part of the
      body of the stomach wrapped in a peritoneal sac herniate into the mediastinum, is
      a relatively uncommon entity. It tends to grow progressively and may become so
      large as to lead to symptoms of intrathoracic organ compression. In some
      exceptional cases, the entire stomach together with other abdominal viscera might
      herniate through the hiatus into the thorax. Paraesophageal hiatus hernias are
      characterised clinically by vague symptomatology, absent gastro-oesophageal
      reflux, and possible onset of gastric volvulus, generally without consequent
      incarceration of the portion of the herniated organ. Such an event is uncommon
      but dangerous and life-threatening. These cases often require resection of the
      incarcerated viscera, followed by hiatoplasty and Nissen fundoplication. The
      authors report on the case of a patient presenting with acute abdomen as a result
      of incarcerated and perforated para-oesophageal hiatus hernia.

PMID- 12239771
TI  - Benign multicystic mesothelioma of the peritoneum: a case report.
AB  - The aim of this study is to report the experience of a case of benign multicystic
      mesothelioma of the peritoneum presented with acute appendicitis symptomatology.
      A 28 years old man with right lower and upper abdominal pain was admitted into
      hospital. Because of the clinical picture, the symptomatology and the
      leukocytosis a diagnosis of acute appendicitis was made and the patient underwent
      appendicectomy according to Mc Burney. At laparotomy some cc of purulent fluid
      were sucked and a cystic mass that contained clear fluid was revealed. In
      consequence of the incidental diagnosis a following middle laparotomy was made
      with a careful surgical excision of the mass and of the appendix. Macroscopically
      the lesion was identified like a neoplastic mass 25 centimeters in diameter, with
      a multicystic and fibrous-adipose aspect, with cysts 5 centimeters in diameter.
      The cystic spaces were lined by a layer of eptelial cells which presented
      positive reaction for cytokeratin and EMA, whereas endothelium markers were
      absent. The ultrastructural, morphological and immunohistochemical findings were
      diagnostic of a benign multicystic mesothelioma.

PMID- 12239772
TI  - [Spontaneous hematoma of the rectus abdominis muscle. A case report].
AB  - A case of rectus sheath haematoma and essential thrombocytosis during
      anticoagulation treatment is described. The difficulties encountered in reaching
      a clinical, differential diagnosis between rectus sheath haematoma and other
      abdominal acute conditions are stressed. Computed tomography may prevent
      inappropriate surgical treatment and its role is emphasized.

PMID- 12239773
TI  - Transclavicular access as an adjunct to standard cervical incision in the
      treatment of mediastinal goitre.
AB  - There are cases in which resection of cervico-mediastinal goitres requires
      additional thoracic access as an adjunct to standard transverse cervicotomy, and
      typically this takes the form of sternotomy or thoracotomy. The authors propose
      transclavicular access as an alternative to thoracotomy or sternotomy access for
      the removal of such goitres. This technical variant is performed by means of
      resection of the middle third of the clavicle and extraperiosteal
      disarticulation. They report a case of cervicomediastinal or "plunged" goitre
      associated with mediastinal metastasis from a follicular thyroid carcinoma in a
      77-year-old woman, in whom this technical variant was used. They conclude by
      stressing the greater effectiveness, ease of execution and relatively limited
      "aggressiveness" of the technique in comparison with other ways of reaching the
      mediastinum. The variant proves effective in solving a number of technical,
      functional and aesthetic problems.

PMID- 12239774
TI  - Practice management considerations for coding documentation.

PMID- 12239775
TI  - Looking back: menstrual disorders of school-girls in 1913.

PMID- 12239776
TI  - Balance of power. Encouraging physicians to help set the strategic plan.
AB  - Involving the medical staff in hospital strategic planning will go a long way
      toward fostering physicians' loyalty and trust in your administration and board.
      Three case studies illustrate how shared planning is working in the field.

PMID- 12239777
TI  - Show them the data. What do trustees need to know and how do they need to know
      it?
AB  - As trustees' accountability expands, they need to keep up with a growing body of
      institutional information. Unfortunately, too many boards get inundated with raw
      data and don't know what to do with them. That's where "dashboards" and
      "scorecards" that highlight trends and show comparisons of significant indicators
      can make all the difference.

PMID- 12239778
TI  - The Maine squeeze on health coverage. Is Maine's health care crisis a harbinger
      of rural health care's future?
AB  - The state of Maine--mostly rural with an economy supported by small businesses-
      is struggling with a health care insurance crisis. Are Maine's problems a
      harbinger of what's to come in other rural states?

PMID- 12239780
TI  - What do trustees and CEOs need from each other.

PMID- 12239781
TI  - Enron and the duties of the health care trustee.

PMID- 12239782
TI  - Back to basics 3. Making service excellence a priority.

PMID- 12239783
TI  - Smoking & pregnant women.

PMID- 12239784
TI  - Training entry-level nurses.

PMID- 12239785
TI  - NHLBI stops estrogen plus progestin trial.

PMID- 12239786
TI  - From practice to policy.

PMID- 12239787
TI  - Revised guidelines for cervical cancer, asthma screening.

PMID- 12239788
TI  - Astronauts & pregnancy bed rest.

PMID- 12239789
TI  - Fathers & breast feeding.

PMID- 12239790
TI  - The women's health nurse practitioner.

PMID- 12239791
TI  - Preventing group B strep in newborns.

PMID- 12239792
TI  - Confidentiality, communication & compliance.

PMID- 12239793
TI  - Cervical cancer screening among Chinese women.

PMID- 12239794
TI  - Early menopause & self-care.

PMID- 12239795
TI  - ALS vs BLS.

PMID- 12239797
TI  - Dealing with the media.

PMID- 12239796
TI  - Risk management and EMS: what managers need to know.
AB  - Today's emergency service leader is faced with many administrative
      responsibilities. Much of this work involves protecting personnel against injury.
      It also involves reducing the effects of losses. To help reduce such problems,
      the umbrella of risk management and application of the principles of loss control
      should be used. A loss control program can identify existing or potential
      problems and provide the means to reduce or eliminate them. A comprehensive risk
      management program is a systematic method that helps you investigate and identify
      your problem areas and strategize methods to eliminate, prevent or safeguard
      against potential risk. It's an easy, straightforward approach that can provide
      positive results. As an emergency service manager, that's what you want--positive
      results!

PMID- 12239798
TI  - An innovative approach to emergency medical continuing education and quality
      assurance: the Gainesville (FL) fire rescue department.

PMID- 12239799
TI  - 21st century EMS retention strategies.

PMID- 12239800
TI  - Front-line leadership. Chapter 4: Loose cannon.

PMID- 12239801
TI  - How are we doing? Measuring system performance.

PMID- 12239802
TI  - The benefits of electricity: transcutaneous pacing in EMS.
AB  - Transcutaneous temporary pacing offers a noninvasive, rapid and effective way to
      institute ventricular pacing, support the patient's hemodynamics and re-establish
      perfusion. Prehospital clinicians can easily and rapidly initiate external pacing
      in an emergency. The two most common reasons for using temporary pacing to
      maintain an optimal cardiac output are when the patient has a bradycardia with
      inadequate perfusion or is asystolic. The introduction of pediatric pacing
      electrodes makes pacing of infants and small children possible. Although the
      effectiveness of noninvasive pacing in children is variable and the need is
      infrequent, the technique can be lifesaving in certain conditions. The use of
      multifunction defibrillation-cardioversion-pacemaker electrodes allows the
      prehospital clinician to rapidly switch between therapies as required.

PMID- 12239803
TI  - Home healthcare: expanding the scope.

PMID- 12239804
TI  - AEDs: does the early defibrillation standard of care leave kids out?

PMID- 12239805
TI  - Emergency management of cardiac injuries.
AB  - Cardiac trauma is not usually treatable in the field. EMS providers must
      recognize the possibility of cardiac trauma rapidly and evacuate the patient to
      an appropriate facility. Most therapy for cardiac trauma requires an operating
      room, preferably with cardiopulmonary bypass capability. Basic patient care
      should occur en route to the treatment facility. Ensure that the airway is
      intact, control respirations and bleeding, and restore circulatory volume to a
      pressure of about 100 systolic. Advanced providers should re-expand any
      associated tension pneumothorax and ensure the chest wall is stable. Consider
      early intubation, since operative intervention is likely.

PMID- 12239806
TI  - Automated external defibrillators: the Singapore perspective.

PMID- 12239807
TI  - It's all in the palm of your hand. Part 2: Palm EMS software.

PMID- 12239808
TI  - Alabama benchmarking project improves stroke treatment.

PMID- 12239809
TI  - Disparities in providing care should be easy to spot, says report.

PMID- 12239810
TI  - Algorithm identifies children with special health care needs.

PMID- 12239811
TI  - AHRQ posts free software for hospital benchmarking.

PMID- 12239812
TI  - [Protein C--a new opening in the treatment of sepsis syndrome].

PMID- 12239813
TI  - [Psychotropic drugs and the risk of arrhythmias].

PMID- 12239814
TI  - [Intestinal parasite infections].

PMID- 12239815
TI  - [Skeletal health during childhood and adolescence].

PMID- 12239816
TI  - [Acute disseminated encephalomyelitis].

PMID- 12239817
TI  - [An ectopic liver tissue causing a severe respiratory insufficiency in a
      newborn].

PMID- 12239818
TI  - [Are there differences between beta blocking agents?].

PMID- 12239819
TI  - [Not much poisonous metals are dissolved from accidentally ingested button-type
      batteries].

PMID- 12239820
TI  - [Multiple problems in a patient with rheumatoid arthritis].

PMID- 12239821
TI  - [The physician as a patient].

PMID- 12239822
TI  - [Desensitization therapy].

PMID- 12239823
TI  - [Nutritional counseling and precautions for the future mother].

PMID- 12239824
TI  - [Searching for lost fatherhood].

PMID- 12239825
TI  - [Eating is also incorporating values].

PMID- 12239826
TI  - [Diet diversification, a key step].

PMID- 12239827
TI  - [Eating and growing, a question of pleasure].

PMID- 12239828
TI  - [Nutrition in the day care nursery].

PMID- 12239829
TI  - [Public health stakes in school food services].

PMID- 12239830
TI  - [Balanced nutrition and respect for cultural diversity].

PMID- 12239831
TI  - [Pastry shops at the hospital].

PMID- 12239832
TI  - [Incarceration at the Alexander juvenile detention center, the insulin-dependent
      diabetic adolescent].

PMID- 12239833
TI  - [Emergencies. 2/7 Esophageal atresia].

PMID- 12239834
TI  - [Correction of visual disorders is optimal between 6 and 18 months].

PMID- 12239835
TI  - A pilot study on the seroprevalence of parvovirus B19 infection.
AB  - BACKGROUND & OBJECTIVES: Human parvovirus B 19 (PVB 19) causes aplastic crisis in
      children with congenital haemolytic anaemia, erythema infectiosum, abortion and
      stillbirth. Since data on PVB 19 prevalence is lacking in India, a pilot study
      was undertaken to estimate the prevalence of IgG antibody in children and adults.
      METHODS: The samples were obtained from children attending our hospital and from
      volunteer blood donors, majority of whom were from south India. They included 45
      children aged 1-5 yr, 39 aged 6-10 yr, 42 aged 11-15 yr and 100 healthy blood
      donors > 15 yr of age. Sera were tested for the presence of antibody to PVB 19
      using a commercial enzyme immuno assay (EIA). RESULTS: Of 226 samples tested, 113
      (50%) were positive for PVB 19 IgG. The prevalence of antibody increased from 8.9
      per cent at 1-5 yr to 70 per cent in those > 15 yr: the median age of infection
      was between 6 and 15 yr. Sex and domiciliary status did not have significant
      effect on the prevalence of antibody. The IgG antibody index increased
      significantly with age, suggesting repeated exposure to the virus. INTERPRETATION
      & CONCLUSION: This seroprevalence study indicates that large numbers of
      individuals show exposure to PVB 19 virus. The exposure as indicated by IgG
      positivity is seen to increase with age. The IgG negative individuals may be
      considered to be at risk of developing infections due to PVB 19.

PMID- 12239836
TI  - Development of monoclonal antibody based antigen capture ELISA to detect
      chikungunya virus antigen in mosquitoes.
AB  - BACKGROUND & OBJECTIVES: Chikungunya (CHIK) virus has caused numerous large
      outbreaks in India. No active or passive surveillance has been carried out since
      the last epidemic which occurred in 1971. For active surveillance, it is
      necessary to have a test, which can detect the virus from a large number of field
      collected mosquitoes. METHODS: The present study describes the standardization of
      monoclonal antibody (MAb) based antigen capture ELISA to detect chikungunya virus
      antigen from the mosquitoes. CHIK virus antigen from suspension of experimentally
      infected mosquitoes and their progeny was captured on mouse polyclonal antibody,
      while biotinylated CHIK Mab was used as a probing antibody. CHIK virus antigen in
      the head squashes of virus inoculated mosquitoes was detected using indirect
      immunofluorescence antibody (IFA) test for confirmation of ELISA results.
      RESULTS: The ELISA test was sensitive enough to detect antigen even if a small
      fraction of a single infected mosquito homogenate was incorporated in the test.
      The IFA test failed to detect CHIK antigen in 10 and 25 microliters of suspension
      whereas with ELISA it was detected in all the samples. Progeny of Aedes aegypti
      and Ae. albopictus mosquitoes infected with chikungunya virus did not show the
      possibility of existence of transovarial transmission. INTERPRETATION &
      CONCLUSION: This test is rapid and simple since it can be completed in two days
      as compared to the conventional mosquito inoculation and IFA techniques, which
      require at least 10 days. There is an additional advantage with this test that a
      large number of samples can be processed, and the remaining homogenate of the
      mosquitoes can be used for screening other viruses. Experimental data raised
      using this test showed that transovarial transmission of this virus does not
      occur in these vector species.

PMID- 12239837
TI  - A localised outbreak of Vibrio cholerae O139 in Kolkata, West Bengal.
AB  - BACKGROUND & OBJECTIVES: An explosive outbreak of diarrhoeal disease which
      occurred in the Baishnabghata, Patuli area of Kolkata Municipal Corporation
      during September 28 to October 12, 2000, was investigated by a team from the
      National Institute of Cholera and Enteric Diseases, Kolkata, to identify the
      causative agent and determine the antimicrobial susceptibility pattern. METHODS:
      Clinical and epidemiological data were collected from domiciliary cases and also
      from patients attending two medical camps that had been set up for the purpose.
      Stool and water samples were collected for isolation of diarrhoeagenic pathogens.
      RESULTS: A total of 710 cases of diarrhoea occurred with an attack rate of 7.1
      per cent; majority were adults. All 6 faecal samples and 2 water samples
      collected, were positive for Vibrio cholerae O139. The strains were uniformly
      (100%) susceptible to the commonly used drugs for cholera such as tetracycline,
      norfloxacin, ciprofloxacin, co-trimoxazole and nalidixic acid but resistant
      (100%) to furazolidone and ampicillin. INTERPRETATION & CONCLUSION: This is the
      first localised outbreak of V. cholerae O139 in Kolkata since the devastating
      epidemic in 1992. Extensive chlorination of all water sources resulted in a
      dramatic decline of the outbreak. The appearance of resistance in V. cholerae
      O139 to furazolidone is a matter of great concern since this drug is used for the
      treatment of cholera in children and pregnant women.

PMID- 12239838
TI  - Prevalence of extended spectrum beta lactamase producing gram negative bacteria
      in a tertiary care hospital.
AB  - BACKGROUND & OBJECTIVES: Extended spectrum beta lactamase (ESBL) producing Gram
      negative bacteria are increasingly being associated with hospital infections
      thereby rendering all beta lactams, except carbapenems ineffective in the
      treatment of infections related to these organisms. A knowledge about their
      prevalence is essential to guide the appropriate antibiotic treatment of severe
      infections in hospitalized patients. The present work was carried out to study
      the prevalence of ESBL producing Gram negative bacteria in a tertiary care
      hospital. METHODS: A total of 678 Gram negative bacteria were included in the
      study. They were isolated from various clinical samples obtained from indoor
      patients admitted to the All India Institute of Medical Sciences, New Delhi
      during March to June 2001. These isolates were screened for ESBL production by
      the inhibitor based test recommended by the National Committee for Clinical
      Laboratory Standards (NCCLS) using Klebsiella pneumoniae ATCC 700603 as positive
      control and Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 as
      negative controls. RESULTS: Out of the 678 strains tested, 458 (68%) were found
      to be ESBL producers. Among the bacterial species, ESBL production was most
      common in Klebsiella spp. (80%). The proportion of ESBL positive isolates was
      highest from intensive care units (79%), followed by Medical Oncology (75%),
      Medical (54%) and Surgical wards (50%). INTERPRETATION & CONCLUSION: A high
      prevalence of ESBL positive isolates was found in our hospital. This has
      important implications as carbapenems remain the only choice of treatment for
      infections caused by these organisms. The control measures include judicious use
      of antibiotics and implementation of appropriate infection control measures to
      control the spread of these strains in the hospital.

PMID- 12239839
TI  - Influence of HLA compatibility on renal graft survival using live unrelated &
      cadaver donors in India.
AB  - BACKGROUND & OBJECTIVES: Living unrelated donor (LURD) renal transplantation has
      shown a rising trend over the last 5 yr at our center following the passing of
      The Transplantation of Human Organs Act by the Government of India in 1994. In
      this paper, the results of LURD and cadaver (CAD) donor renal transplantation are
      compared. We have also looked into factors that have a bearing on graft survival
      such as the extent of HLA mismatch (MM), infections, acute rejections (AR), donor
      age and sex. METHODS: A total of 42 LURD and 25 CAD renal transplants performed
      between March 1994 and February 1999 has been included in the study. HLA typing,
      panel reactive antibody (PRA) screening and T and B cell cross match assay were
      performed by the complement dependent cytotoxicity (CDC) method for all patients.
      RESULTS: The graft survival rates were generally higher in the LURD category as
      compared to the CAD group and were significant at 6 month period (90 vs 56%, P =
      0.002). A follow up of the patients up to 60 months revealed a matching effect
      since the 3, 4 allele MM group had better survival rates as compared to the 5, 6
      MM group. Twenty six of the 67 recipients (39%) experienced episodes of acute
      rejection (AR). Patients with 3, 4 MM had fewer such episodes than those with 5,
      6 allele MM (P < 0.05). Of the 32 deaths, 20 were those with a functional kidney,
      of which 15 were caused by severe infections. INTERPRETATION & CONCLUSION: Better
      HLA matching ensures fewer episodes of rejection and better long term graft
      survival in comparison to the poorly matched grafts. The graft survival for LURD
      recipients was appreciably higher than that of CAD recipients.

PMID- 12239841
TI  - [Breast feeding is not always enough!].

PMID- 12239840
TI  - Bile flow response to repetitive heat stress in rats.
AB  - BACKGROUND & OBJECTIVES: Heat stress produces loss of absorptive surface area of
      the small intestine, including the ileum which is the site of bile acid
      absorption. This may cause diarrhoea on account of the possible bile acid
      malabsorption. To explore this possibility, the effect of high ambient
      temperature exposure on bile flow was studied in the warm acclimated albino rats.
      METHODS: Following heat exposure at 38 +/- 0.5 degrees C for 4 h/day, for up to 5
      consecutive days, bile flow in the rats was measured gravimetrically under
      pentobarbital-induced anaesthesia, at steady rectal temperature (37 +/- 0.7
      degrees C), and flow characteristics and rate were studied. RESULTS: The bile
      flow increased with the rise in rectal temperature (Tre) in an anaesthetized
      animal but, the relationship between the two was not linear; the flow nearly
      ceased if rectal temperature exceeded 43 degrees-44 degrees C. At steady, near
      normal, rectal temperature, bile flow showed fluctuations and, repetitive heat
      exposure led to a significant increase in bile flow. INTERPRETATION & CONCLUSION:
      Exposure to high ambient temperature modulates liver secretory function to
      enhance bile flow rate and increase bile acid absorptive load on the small
      intestine, whose absorptive function is known to be adversely affected in heat
      stress.

PMID- 12239842
TI  - [Imaging and therapy of rheumatoid arthritic shoulder].

PMID- 12239843
TI  - [Prenatal ultrasound screening and urinary tract findings].

PMID- 12239844
TI  - [Pulmonary edema caused by extubation-provoked laryngeal spasm].

PMID- 12239845
TI  - [Doughnuts are dangerous for a Finnish soldier].

PMID- 12239846
TI  - [Tibial fracture in a blue-eyed boy].

PMID- 12239847
TI  - [The "omics" are coming--one gene is not enough anymore].

PMID- 12239848
TI  - [From gene chips to biochips: challenges and possibilities of the new
      biotechnology].

PMID- 12239849
TI  - [Gene chip technique and associated bioinformatics].

PMID- 12239850
TI  - [Comparison of genomes and phenotypes between species].

PMID- 12239851
TI  - [Proteomics and its applications].

PMID- 12239852
TI  - [Ligandomics--a tool for the development of targeted treatments].

PMID- 12239853
TI  - [The odd omes and omics].

PMID- 12239854
TI  - Infection control. It's in the blood.

PMID- 12239855
TI  - Should the law on mental capacity be reformed?

PMID- 12239856
TI  - Scope for the future.

PMID- 12239857
TI  - Alcohol last orders.

PMID- 12239858
TI  - Post-coitally yours.

PMID- 12239859
TI  - Nurses' and students' perceptions of care: a phenomenological study.
AB  - This article describes a phenomenological study that aimed to explore 15 nurses'
      and six nursing students' attitudes towards care and caring. Using a qualitative
      approach, their lived, expressed experiences were documented from tape-recorded
      interviews. Significant statements were collected and arranged into themes, with
      examples from the transcripts providing an insight into the nurses' beliefs and
      feelings. The findings and attitudes expressed underline and reinforce the
      complexity of the phenomenon of caring. Certain findings are consistent with
      those in the literature, but the study shows new insights on two themes--'taking
      risks' and 'supporting care'. The author suggests that the findings have
      implications for nurse tutors, and that care and caring should be placed at the
      centre of the nursing curriculum.

PMID- 12239860
TI  - Integrated cancer care: linking medicine and therapies.
AB  - Many patients receiving conventional cancer care benefit from complementary
      therapies. A cancer centre offering complementary therapies tailors them to meet
      each patient's needs and complement conventional therapies. To integrate care, it
      was important to gain the trust and cooperation of colleagues in conventional
      disciplines. This was done by focusing on thorough needs assessments and
      evaluation to demonstrate the value of the therapies on offer.

PMID- 12239861
TI  - Extended training equips nurses to undertake diagnostic hysteroscopy.
AB  - In 2001, consultant gynaecologists at Bradford Hospitals NHS Trust extended the
      services in the outpatient hysteroscopy department from being purely diagnostic
      to offering simple operative procedures. As a result, it was decided that two
      existing nurse facilitators would undertake the diagnostic work. To equip them
      with the necessary skills and competence, an advanced practice hysteroscopy
      module was developed in collaboration between the hospital and the University of
      Bradford. Successful completion of academic and practical work allows nurses to
      practise diagnostic hysteroscopy independently. Feedback from patients about the
      service now offered by nurses has been positive.

PMID- 12239862
TI  - Winter support for older people with mental illness.
AB  - Older people with mental health problems are often reluctant to use day-care
      facilities in the winter. This can often have a detrimental effect on their
      health and put further pressures on overstretched facilities. The authors
      describe a pilot scheme at a mental health trust in London that provided
      assertive outreach to service users who found it difficult to engage with
      services, encouraging them to take part in therapeutic activities and to attend
      the day centre. After six months the health of the participants showed
      improvements.

PMID- 12239863
TI  - Cardiopulmonary resuscitation. External pacing.

PMID- 12239864
TI  - Myths and science of dietary fat and coronary heart disease.

PMID- 12239865
TI  - Food record charts.

PMID- 12239866
TI  - Nutritional supplementation in unwell elderly people.

PMID- 12239867
TI  - Nutrition and nurse education.

PMID- 12239868
TI  - Day in the life.

PMID- 12239869
TI  - Under attack.

PMID- 12239870
TI  - Sobering thoughts.

PMID- 12239871
TI  - That's the spirit.

PMID- 12239872
TI  - The qualities and skills of practice developers.
AB  - AIM: To explore and describe the activities and approaches that constitute
      practice development by providing an insight into the qualities and skills
      exhibited by staff in practice development roles. METHOD: This involved examining
      177 articles, plus data collected during focus group interviews with 60 staff
      around the UK and telephone interviews with 25 clinical staff. The focus groups
      and telephone interviews formed part of an earlier published study Garbett and
      McCormack (2002). RESULTS: A range of skills and qualities were highlighted.
      These include being effective, having vision, being motivated, empathic,
      experiential, cognitive political, communicative, facilitative and possessing
      clinical skills. CONCLUSION: The work of practice developers is of central
      importance in the light of NHS policy developments, such as the NHS Plan or the
      response to the Bristol inquiry.

PMID- 12239873
TI  - A rehabilitation framework for patient-focused care.
AB  - Rehabilitation is an evolving and developing collaborative discipline. The
      nursing role is pivotal to the success of the government's agenda for service
      development and modernisation. This article presents a new framework of
      rehabilitation as a mechanism for clarifying and understanding the value of
      nursing's all-encompassing, complex role. The framework aims to contribute to the
      developing body of knowledge relating to the specialty, offering an opportunity
      for nurses to challenge their practice through a systematic re-evaluation of
      their approach.

PMID- 12239875
TI  - Close to the bone.

PMID- 12239874
TI  - Substance misuse and mental health: an overview.
AB  - Patients with dual diagnosis of substance misuse and mental health problems
      present many challenges for nurses, as their complex needs make them difficult to
      manage and treat. The author provides an overview of the nature and extent of the
      problem and a framework for nursing interventions.

PMID- 12239876
TI  - [Why do the oral contraceptive pills not work?].

PMID- 12239877
TI  - [Alcohol and female steroid hormones].

PMID- 12239879
TI  - [Is one month long education enough to master the ultrasound diagnostics of
      abdominal diseases?].

PMID- 12239878
TI  - [Metabolic crisis in an infant--is the problem in the mitochondria?].

PMID- 12239880
TI  - [When is somnolence assessed to be excessive?].

PMID- 12239881
TI  - [Bleeding problems of a patient with hypothyroidism].

PMID- 12239882
TI  - [The dangers of sex].

PMID- 12239883
TI  - [The chlamydia epidemics is continuing--what should be done?].

PMID- 12239884
TI  - [Changing epidemiological profile and treatment of syphilis and gonorrhea].

PMID- 12239885
TI  - [Patient with a sexually transmitted disease visiting the health care center].

PMID- 12239886
TI  - [Papilloma viruses on the mucous membranes].

PMID- 12239887
TI  - [A vaccine against papillomavirus infections and cancer].

PMID- 12239888
TI  - [Pregnancy and labor of a HIV-positive woman].

PMID- 12239889
TI  - [Diagnostics and drug therapy of multiple sclerosis].

PMID- 12239890
TI  - Toward an interpretation of dynamic neural activity in terms of chaotic dynamical
      systems.
AB  - Using the concepts of chaotic dynamical systems, we present an interpretation of
      dynamic neural activity found in cortical and subcortical areas. The discovery of
      chaotic itinerancy in high-dimensional dynamical systems with and without a noise
      term has motivated a new interpretation of this dynamic neural activity, cast in
      terms of the high-dimensional transitory dynamics among "exotic" attractors. This
      interpretation is quite different from the conventional one, cast in terms of
      simple behavior on low-dimensional attractors. Skarda and Freeman (1987)
      presented evidence in support of the conclusion that animals cannot memorize odor
      without chaotic activity of neuron populations. Following their work, we study
      the role of chaotic dynamics in biological information processing, perception,
      and memory. We propose a new coding scheme of information in chaos-driven
      contracting systems we refer to as Cantor coding. Since these systems are found
      in the hippocampal formation and also in the olfactory system, the proposed
      coding scheme should be of biological significance. Based on these intensive
      studies, a hypothesis regarding the formation of episodic memory is given.

PMID- 12239891
TI  - The Theory of Event Coding (TEC): a framework for perception and action planning.
AB  - Traditional approaches to human information processing tend to deal with
      perception and action planning in isolation, so that an adequate account of the
      perception-action interface is still missing. On the perceptual side, the
      dominant cognitive view largely underestimates, and thus fails to account for,
      the impact of action-related processes on both the processing of perceptual
      information and on perceptual learning. On the action side, most approaches
      conceive of action planning as a mere continuation of stimulus processing, thus
      failing to account for the goal-directedness of even the simplest reaction in an
      experimental task. We propose a new framework for a more adequate theoretical
      treatment of perception and action planning, in which perceptual contents and
      action plans are coded in a common representational medium by feature codes with
      distal reference. Perceived events (perceptions) and to-be-produced events
      (actions) are equally represented by integrated, task-tuned networks of feature
      codes--cognitive structures we call event codes. We give an overview of evidence
      from a wide variety of empirical domains, such as spatial stimulus-response
      compatibility, sensorimotor synchronization, and ideomotor action, showing that
      our main assumptions are well supported by the data.

PMID- 12239892
TI  - A sensorimotor account of vision and visual consciousness.
AB  - Many current neurophysiological, psychophysical, and psychological approaches to
      vision rest on the idea that when we see, the brain produces an internal
      representation of the world. The activation of this internal representation is
      assumed to give rise to the experience of seeing. The problem with this kind of
      approach is that it leaves unexplained how the existence of such a detailed
      internal representation might produce visual consciousness. An alternative
      proposal is made here. We propose that seeing is a way of acting. It is a
      particular way of exploring the environment. Activity in internal representations
      does not generate the experience of seeing. The outside world serves as its own,
      external, representation. The experience of seeing occurs when the organism
      masters what we call the governing laws of sensorimotor contingency. The
      advantage of this approach is that it provides a natural and principled way of
      accounting for visual consciousness, and for the differences in the perceived
      quality of sensory experience in the different sensory modalities. Several lines
      of empirical evidence are brought forward in support of the theory, in
      particular: evidence from experiments in sensorimotor adaptation, visual "filling
      in," visual stability despite eye movements, change blindness, sensory
      substitution, and color perception.

PMID- 12239893
TI  - Initiative proves laughter is the best medicine.

PMID- 12239894
TI  - Emergency contraception and sexual assault. Assessing the moral approaches in
      Catholic teaching.

PMID- 12239895
TI  - The power of the soul. Business expertise is not enough; executives in Catholic
      health care must be spiritual leaders, too.
AB  - After more than 20 years in health care, including at least a decade in
      leadership, this day was perhaps my darkest on the job. Since becoming chief
      operating officer of this Catholic hospital, I, with the help of my management
      team, had struggled to find answers to apparently overwhelming financial and
      operational challenges. I had been forced to make tough decisions in the pursuit
      of financial stability. In round-the-clock meetings, my team and I (with the
      assistance of a consulting firm whose specialty was turnarounds) had dissected
      every aspect of the operation. I had compared the performance of the hospital to
      industry benchmarks, never wanting to be unfair in expecting more from my staff
      than others had accomplished. In fact, in every decision I made I tried to be
      fair, weighing the different interests at stake before choosing a course of
      action--all the while knowing that, no matter what, I would make someone angry.
      Those around me, instead of recognizing my efforts to be fair, seemed to feel
      they had been betrayed. The whole organization was dispirited. My medical staff
      support was eroding as physicians refocused their practices at other facilities
      not faced with the challenges I had to address. Local leaders roundly criticized
      me for what they saw as abandoning the community's needs in the interest of
      serving the hospital and its bottom line. Then came the most hurtful news of all.
      My employees had filed a petition for representation by a union. It was not that
      I had a problem with organized labor. But how could an organization that I led
      have come to a place where the staff felt so abandoned by my leadership that they
      needed someone else to represent and protect their interest? Hadn't I tried hard
      to educate the staff about the changes in health care reimbursement? Hadn't I
      told them that the very existence of the hospital was at stake? Didn't they see
      how hard I worked, how much I cared? What was I to do now?

PMID- 12239896
TI  - Integrative health care. A Catholic system develops a new approach to the art of
      healing.

PMID- 12239897
TI  - Combining health care and housing. A hospital partners with Mercy Housing Midwest
      to construct apartments for the local low-income elderly.

PMID- 12239898
TI  - Effective organizations are driven by values. Survey data show that values-driven
      Catholic health care facilities are effective facilities.

PMID- 12239899
TI  - Change as a creation story. A theoretical tool plots the dynamics of
      organizational change.

PMID- 12239900
TI  - Creating effective mission statements. Recapturing the power and glory of mission
      is possible with careful planning and implementation.

PMID- 12239901
TI  - Community networks. Xavier Medical Clinic Tulsa, OK.

PMID- 12239902
TI  - Results of laparoscopic versus open resections for non-early rectal cancer in
      patients with a minimum follow-up of four years.
AB  - BACKGROUND/AIMS: Laparoscopic rectal resection for malignancy is still debated.
      Concern has been expressed regarding the lack of significant data from larger
      patient series with longer periods of follow-up. The aims of this study were to
      compare long-term outcome with a minimum follow-up of four years in unselected
      patients undergoing either laparoscopic rectal resection or open rectal resection
      for cancer. METHODOLOGY: From May 1992 to August 1997 all electively admitted
      patients with rectal cancer were included in a prospective non-randomized study.
      Written information was submitted to each patient and the location in each group
      (laparoscopic or open) was related to the patient's choice. The inclusion
      protocol criteria excluded T1 tumors. All 68 T2-T4 patients underwent
      preoperative radiotherapy (5.040 cGy), completed with chemotherapy in selected
      cases (patients below 70 years of age). Long-term results were compared between
      the two groups. Follow-up time of both groups ranged between 48 and 96 months
      (mean, 49.4 months). RESULTS: Excluding patients who underwent a palliative
      resection or conversion to open surgery and deaths not related to cancer, 53 pts
      (29 laparoscopic rectal resection, 24 open rectal resection) out of 68 are
      available and are the object of this study. No patient was lost to follow-up. No
      wound recurrence was observed. The local recurrence rate after laparoscopic
      rectal resection was 24.1% vs. 25% after open rectal resection (P = 0.799).
      Distant metastases occurred in 20.7% of patients in the LLR group (laparoscopic
      rectal resection) vs. 25% in the ORR group (open rectal resection) (P = 0.980).
      Cumulative survival probability after laparoscopic rectal resection and open
      rectal resection was 0.690 and 0.625 (P = 0.492), respectively. Cumulative
      survival probability for Duke's stage A, B and C in the LRR group vs. the ORR
      group was 1.000 vs. 0.900 (P = 0.585), 0.667 vs. 0.636 (P = 0.496) and 0.429 vs.
      0.445 (P = 0.501), respectively. Sixteen laparoscopic rectal resection patients
      (55.2%) and 12 open rectal resection patients (50%) are presently disease free (P
      = 0.979). CONCLUSIONS: Long-term results after laparoscopic resection of rectal
      cancer were comparable to those after conventional resection, with a trend in
      favor of the laparoscopic approach that does not reach a statistically
      significant difference, possibly due to the limited size of the sample.

PMID- 12239903
TI  - The media of rapid urease test influence the diagnosis of Helicobacter pylori.
AB  - BACKGROUND/AIMS: The influence of different media on the validity of the rapid
      urease test, including accuracy, reaction time and cost-effectiveness is
      evaluated. METHODOLOGY: Biopsies were obtained from the antral and body mucosa of
      100 KMUH patients (51 men, 49 women; mean age: 54.0 years, range: 21-79 years
      old) undergoing gastroendoscopy due to dyspepsia. None of the patients had
      received any Helicobacter pylori eradicating treatment, nor any other antibiotic
      or bismuth treatment in the previous one month, nor had they had any type of
      gastric operation in the past. Helicobacter pylori status was evaluated by seven
      different tests: culture, histology, home-made rapid urease test, 13C-urea breath
      test, and three different commercially available rapid urease tests--including
      the CLO test, the ProntoDry test, and the Pyloriset Urease test. Helicobacter
      pylori status was defined as positive when the culture was positive or if
      concordance of two of the other three tests (histology, homemade rapid urease
      test and 13C-urea breath test) was positive. RESULTS: Three different rapid
      urease tests have similar sensitivities (97.3% vs. 100% vs. 100%) and
      specificities (98.4% vs. 96.8% vs. 98.2%), and accuracy (98.4% vs. 96.8% vs.
      98.2%). But the reaction time was longer in the CLO test than for the other two
      rapid urease tests (22.3 vs. 5.6 vs. 10.1 minutes) (P < 0.05). The ProntoDry test
      and the Pyloriset Urease test also have more rapid positive rate than CLO test.
      However, in vitro study, three tests show similar rapidity of positive reaction
      at different densities of Helicobacter pylori. CONCLUSIONS: These three tests
      have practical advantages for physicians who need a rapid and accurate method of
      diagnosing Helicobacter pylori infections. The ProntoDry test and Pyloriset
      Urease test have degrees of accuracy similar to the CLO test, but results are
      obtained more rapidly and they are cheaper. Furthermore, The ProntoDry test can
      be stored at room temperature and thereby save on the storage expense.

PMID- 12239904
TI  - Clinical and biochemical features and therapy responses in primary biliary
      cirrhosis and primary biliary cirrhosis-autoimmune hepatitis overlap syndrome.
AB  - BACKGROUND/AIMS: Primary biliary cirrhosis and autoimmune hepatitis are two main
      immune-mediated liver diseases. Some patients display characteristics of both
      diseases, so called overlap syndrome. The aims of this study were to investigate
      and to compare the clinical and laboratory features and responses to therapy in
      primary biliary cirrhosis and overlap syndrome. METHODOLOGY: Twenty-three
      patients with primary biliary cirrhosis (21 females, 2 males; median age: 50
      years) and 20 with primary biliary cirrhosis-autoimmune hepatitis overlap
      syndrome (18 females, 2 males; median age: 44 years) were included in the study.
      All patients with primary biliary cirrhosis were treated with ursodeoxycholic
      acid. Of patients with overlap syndrome, 16 were treated with ursodeoxycholic
      acid and 4 with ursodeoxycholic acid plus prednisolone. Histological findings
      laboratory and clinical data were compared at the baseline and at the 2nd year of
      treatment. RESULTS: Fatigue and pruritus were the most frequent and comparable
      symptoms in each group. Serum ALT, AST, gamma-glutamyl transpeptidase, total
      protein, globulin and gammaglobulin levels were higher in patients with overlap
      syndrome than those in patients with primary biliary cirrhosis. At the end of the
      2nd year of the treatment, ALT normalization was achieved in 12 (52%), alkaline
      phosphatase in 7 (30%) patients with primary biliary cirrhosis. One of the non
      responders to ursodeoxycholic acid therapy had the histological findings of
      overlap syndrome in her control biopsy. Fibrosis score deteriorated in 50% of the
      patients. Of ursodeoxycholic acid-treated overlap syndrome patients, 11 completed
      2 years of treatment. Three patients were biochemically non-responsive and
      prednisolone was added to their regimen. Of the remaining 8 patients, 7 (64% of
      total patients) had normal ALT. Three patients had worse fibrosis score comparing
      the onset of the treatment. Six of 7 (86%) patients who were given
      ursodeoxycholic acid plus prednisolone including ursodeoxycholic acid-non
      responsives had normal ALT and 2 of 6 biopsy-controlled patients display
      deterioration of their fibrosis score. CONCLUSIONS: Biochemical tests tended to
      be higher in patients with overlap syndrome comparing to those with primary
      biliary cirrhosis. Response to ursodeoxycholic acid treatment in patients with
      overlap syndrome was comparable with that obtained in primary biliary cirrhosis.
      Therefore it should be the first-line treatment. Non-responsive patients may
      benefit from the use of ursodeoxycholic acid plus prednisolone combination.

PMID- 12239905
TI  - Endoscopic management of bile duct injuries in 107 patients: experience of a
      Saudi referral center.
AB  - BACKGROUND/AIMS: Management of postcholecystectomy complications has been
      variably discussed. Various options exist but the recent trend has been towards
      the endoscopic retrograde approach favoring a simultaneous diagnostic and
      therapeutic potential. We studied the various endoscopic modalities to evaluate
      the efficacy of this approach. METHODOLOGY: A retrospective analysis was
      conducted of 318 patients referred to the endoscopy department for suspected
      postcholecystectomy complications. A total of 107 patients were identified to
      have biliary injury. The study period extended from May 1982 to April 2000. All
      cases of bile duct injury were evaluated by endoscopic retrograde
      cholangiopancreatography for the feasibility of offering therapy. RESULTS: From a
      total of 107 cases, 123 sites of biliary injury were identified. There were 66
      patients with benign strictures and 57 patients with leaks and another 16
      patients had a combination of leaks and strictures. Endoscopic diagnosis was
      feasible in 98% of patients. Subsequently, 81 patients accounting for 76% of the
      cases were considered for endotherapy and successful healing was shown in 90%.
      Seventy-seven percent of the leaks underwent trial of endoscopic management with
      successful response seen in 93.2% cases. Similar results occurring for strictures
      where 87.2% maintained sustained dilatation from a total of 45 case that had
      attempted endotherapy. There were no complications encountered in any of the
      patients. CONCLUSIONS: Endoscopic retrograde cholangiopancreatography is a safe
      and feasible mode of therapy for patients presenting with suspected bile duct
      injuries. This form of intervention should be considered as the initial step in
      the diagnosis and treatment of postcholecystectomy complications.

PMID- 12239906
TI  - Symptomatic or asymptomatic gallstone disease: is the gallbladder motility the
      clue?
AB  - BACKGROUND/AIMS: Only a minority of gallstone patients develop biliary pain.
      Until now, the factors related to pain have been poorly described. METHODOLOGY:
      In a prospective study, gallstone patients without acute cholecystitis,
      pancreatitis or hepatobiliary obstruction were classified into typical
      symptomatic (type-I, n = 44), atypical symptomatic (type-II, n = 14) and
      asymptomatic (type-III, n = 29) using a standardized questionnaire (8 items for
      typical, 3 items for unspecific complaints). Demographic data, body mass index,
      number and size of gallstones, gallbladder wall thickness and motility after a
      standardized meal were assessed (ultrasound study) in patients, results were
      compared to controls without hepatobiliary disease. RESULTS: The gallbladder
      contractility was similar to controls in type-I (67%) but diminished in II (55%)
      and III (46%, P < 0.05). Type-I showed lower fasting (P < 0.05) and postprandial
      gallbladder volumes (P < 0.0005) and was associated with smaller stones (P <
      0.0001), younger age (P < 0.0001) and female gender (P < 0.001). Body mass index,
      stone number and gallbladder wall thickness was not related to pain. CONCLUSIONS:
      A sluggish gallbladder may protect from biliary pain. The consideration of
      gallbladder motility and further risk factors (small stones, younger age and
      female gender) may help to predict the clinical course of gallstone patients,
      define atypical complaints as biliary related and select patients for treatment.

PMID- 12239907
TI  - Reconstruction of small bile ducts using a parachute technique.
AB  - Benign or malignant stricture of extrahepatic bile ducts may result when small
      intrahepatic bile ducts are anastomosed to the jejunal loop after resection of
      extrahepatic bile ducts, hepatic parenchyma, and intrahepatic bile ducts. We
      applied a parachute technique, which has been used for fine vascular anastomosis,
      to hepaticojejunostomy in eight patients with either extrahepatic bile duct
      carcinoma or intrahepatic cholangiocellular carcinoma. One to four small bile
      ducts were anastomosed to the jejunal loop. No patient experienced a complication
      due to this anastomosis. Postoperative elevation of the serum bilirubin was
      transient, and all patients were discharged within 36 days after surgery.
      Although the follow-up period in this series is not yet long enough to evaluate
      the long-term outcome of this technique, the ease of the hepaticojejunostomy and
      good short-term results warrant farther clinical investigation of this technique.

PMID- 12239908
TI  - Carcinoma of the hepatic hilus developing 21 years after biliary diversion for
      choledochal cyst: a case report.
AB  - Cyst excision and biliary diversion are generally accepted operative procedures
      for choledochal cysts to prevent biliary tract carcinoma. We report herein a case
      of carcinoma of the hepatic hilus developing in the hepatic hilus 21 years after
      biliary diversion for a choledochal cyst. A 62-year-old female was admitted to
      our hospital because of refractory cholangitis. A diagnosis of carcinoma of the
      hepatic hilus was made based on a cholangiogram, biliary fiberscopy and biopsy.
      She underwent a curative resection of the tumor. Biliary tract carcinoma may be a
      late postoperative complications of choledochal cysts. Long-term follow-up of the
      patient is necessary after the primary operation.

PMID- 12239909
TI  - Primary sclerosing cholangitis associated with autoimmune pancreatitis.
AB  - We present 2 cases of primary sclerosing cholangitis complicated with autoimmune
      pancreatitis with narrowing of the pancreatic duct. In both cases, endoscopic
      retrograde cholangiography showed the characteristic findings of primary
      sclerosing cholangitis. In addition, positivity for autoantibody, hypergamma
      globulinemia and narrowing of the pancreatic duct shown on endoscopic retrograde
      pancreatography were noticed in both. They were thu diagnosed as autoimmune
      pancreatitis. Whereas it is well known that primary sclerosing cholangitis is
      often complicated with chronic pancreatitis, it has rarely been studied whether
      the chronic pancreatitis is autoimmune pancreatitis or not. In English
      literature, possibly 7 equivalent cases have been reported so far. In those
      cases, the onset was in the post-prime of life, and the disease was frequently
      accompanied with Sjogren's syndrome, but not with ulcerative colitis; frankly the
      nature of the disease was slightly different from what has traditionally been
      thought as a typical primary sclerosing cholangitis. In primary sclerosing
      cholangitis complicated with autoimmune pancreatitis, the autoimmune mechanism
      seems to be much involved, and thus steroid therapy might be effective as in Case
      2 in our series.

PMID- 12239910
TI  - p53 expression and DNA ploidy pattern in Egyptian colorectal carcinoma.
AB  - BACKGROUND/AIMS: p53 gene mutation occurs in about 50-60% of colorectal carcinoma
      cases. This mostly occurs as a late event in the adenoma-carcinoma sequence.
      These late stages are associated with more aneuploidy compared to adenomas and
      early carcinomas. However there is a controversy regarding the relation between
      p53 overexpression and DNA index. This study was designed to investigate the
      relationship between p53 status and DNA ploidy pattern. METHODOLOGY: Nuclear DNA
      content of paraffin-embedded material from 83 colectomy specimens for colorectal
      carcinoma was measured by flow cytometry. Also, p53 was detected by
      immunohistochemistry in 73 out of the 83 tumor cases using a monoclonal antibody
      that detects both wild and mutant p53 proteins (Biogenex 1801). RESULTS:
      Aneuploidy was identified in 37 cases (46.25%). Tumors with rectal location were
      significantly more aneuploid in comparison to other sites (P = 0.009), p53
      staining showed three patterns: diffuse staining (29 cases), focal (13 cases),
      and negative (31 cases). Diffuse p53 staining was associated with aneuploidy (P =
      0.04). The majority of DNA indices fell within the range 1.1-2.2 (32 out of 37).
      Twenty-one of these had DNA index = 1.1-1.8 (aneuploidy short of tetraploidy)
      significantly associated with diffuse p53 staining compared with peritetraploid
      cases (DNA index 1.8-2.2) (P = 0.034). CONCLUSIONS: p53 immunohistochemistry
      demonstrates two distinct patterns in colorectal carcinoma. Diffuse p53 staining,
      which is associated with aneuploidy short of tetraploidy (DNA index 1.1-1.8), a
      finding which is different from previously published work. Focal p53 staining
      pattern, in contrast, is related to high G2M and more abnormal tetraploid peaks
      but less aneuploidy.

PMID- 12239911
TI  - Adenosquamous carcinoma of the gallbladder.
AB  - BACKGROUND/AIMS: Adenosquamous carcinoma of the gallbladder is relatively rare.
      Its biological behavior and optimal surgical procedure are still controversial.
      METHODOLOGY: Clinicopathological factors and proliferating cell nuclear antigen
      expression were studied in four stage IV adenosquamous carcinoma patients who
      underwent curative surgery between June 1987 and April 2000, comparing those of
      14 stage IV adenocarcinoma patients at the same period. RESULTS: Preoperative
      radiological evaluation disclosed a mass invading to the adjacent organs in all
      cases (liver in 3 cases, and liver and stomach in one case). Three patients (case
      1, 2 and 3: well-differentiated adenosquamous carcinomas) were all alive without
      recurrence in 10, 7, and 2 years after surgery. In contrast, the remaining
      patient (case 4: moderately differentiated adenosquamous carcinoma) with positive
      pathologic factors (lymph node metastasis, vascular invasion, etc) deceased one
      year after surgery due to peritoneal dissemination. When survival rate of
      adenosquamous carcinoma was compared, the prognosis of adenosquamous carcinoma
      was significantly better than that of adenocarcinoma (P = 0.0103). Comparison of
      pathological factors revealed that the frequency of lymph node metastasis was
      significantly higher in adenocarcinoma than in adenosquamous carcinoma (P =
      0.004). Consistent with these findings, the positivity rate of proliferating cell
      nuclear antigen labeling was significantly lower in squamous carcinoma component,
      compared with adenosquamous component (P < 0.0001) or adenocarcinoma (P <
      0.0001). CONCLUSIONS: Even in patients with stage IV adenosquamous carcinoma of
      the gallbladder, a long-term survival may be obtained by curative surgery if the
      squamous component is predominant.

PMID- 12239912
TI  - Immunohistochemical study of collagen synthesis in an in-vitro model of scirrhous
      carcinoma of the stomach.
AB  - BACKGROUND/AIMS: The mechanisms involved in the unique stromal change that occurs
      upon cancer invasion are poorly understood in scirrhous carcinoma of the stomach.
      METHODOLOGY: Three different human gastric cancer cell lines (KATO-III, MKN-28,
      MKN-45) and human fibroblast cells (TIG-101) were co-cultured three-dimensionally
      in collagen gels. The gels, in vitro models of gastric cancer, were immunostained
      by monoclonal antibodies to human placental prolyl 4-hydroxylase (PH, a key
      enzyme of collagen synthesis) and then examined by light and electron microscopy.
      RESULTS: Under co-culture of cancer cells and fibroblasts, cytoplasmic staining
      for PH was observed in both the cancer cells (KATO-III, MKN-28, MKN-45) and
      fibroblasts. No significant difference in the expression patterns of the alpha-
      and beta-subunits of PH was observed not only among the KATO-III, MKN-28 and MKN
      45 cell lines but also between cancer cells and fibroblasts. CONCLUSIONS: These
      findings indicate that both cancer cells and fibroblasts can synthesize collagen
      in gastric cancer models. Moreover, this property may not be a unique
      characteristic of scirrhous gastric cancer cells, but common to gastric cancer
      cells and fibroblasts in vitro.

PMID- 12239913
TI  - Deregulation of G1/S transition is a common event in carcinoma of the ampulla of
      vater.
AB  - BACKGROUND/AIMS: Aberrant expression of cell cycle regulators and subsequent
      deregulation of G1/S transition is one of the most important characteristics of
      human cancer. The aim of this study was to determine the overall pattern of
      deranged expression of the cell cycle regulators involved in the G1/S transition
      in ampullary carcinoma. METHODOLOGY: Using immunohistochemistry, we investigated
      the expression of p21WAF1/CIP1, p27Kip1, p16INK4, cyclin D1, cyclin E, pRb and
      p53 in 14 resected specimens of ampullary carcinoma and defined the proliferative
      activity of each tumor by quantifying Ki-67 antigen. RESULTS: Decreased
      expression of p21WAF1/CIP1, p27Kip1, and p16INK4 was detected in 6 (43%), 11
      (79%), and 4 (29%) tumors, respectively. Four tumors (29%) overexpressed cyclin
      D1 and 8 (57%) overexpressed cyclin E. Eight tumors (57%) overexpressed pRb.
      Aberrant accumulation of p53 was observed in 10 (71%) of the tumors. Overall, the
      expression of two or more of these cell cycle regulators was altered in all of
      the 14 tumors. Decreased p21WAF1/CIP1 expression was related to higher TMN stage
      (P = 0.04) and lymphatic invasion (P = 0.04). The proliferative index was higher
      in tumors with decreased p27Kip expression (P = 0.005), and in tumors with cyclin
      E overexpression (P = 0.06). CONCLUSIONS: Our observations suggest that
      deregulation of G1/S transition is a very common event in ampullary carcinoma,
      and that altered expression of cell cycle regulators is associated with the
      aggressive behavior of this tumor. Correcting the G1/S transition regulatory
      machinery may provide a novel therapy for this malignancy.

PMID- 12239914
TI  - The role of sandostatin LAR in treating patients with advanced hepatocellular
      cancer.
AB  - BACKGROUND/AIMS: The overexpression of somatostatin receptors in the liver of
      some patients with hepatocellular carcinoma is well documented. The daily
      administration of octreotide in patients with advanced hepatocellular carcinoma
      was shown to have a marginal clinical effectiveness. The aim of the study was to
      estimate if and to what extent the administration of octreotide long-acting
      formulation (Sandostatin LAR) improves survival and quality of life in patients
      with advanced unresectable hepatocellular carcinoma. METHODOLOGY: Twenty-eight
      cirrhotic patients (stages A-B) with advanced hepatocellular carcinoma were
      enrolled in the study. Octreoscan scintigraphy for detection of STTR was
      performed in all cases. If it showed intense uptake in the liver, octreotide was
      administered as follows: Sandostatin 0.5 mg subcutaneous every 8 hours for 6
      weeks. At the end of weeks 4-8 Sandostatin LAR 20 mg and at the end of week 12
      and every 4 weeks Sandostatin LAR 30 mg intramuscularly. Patients' follow-up was
      worked out monthly. Thirteen patients unable to receive treatment were used as
      control group. RESULTS: Comparison of results between the 2 groups showed a
      significant difference in the median survival time (31 vs. 16 weeks, p = 0.037)
      and an improvement of quality of life (60% vs. 23.07%). Also, treated group
      showed a 72% reduction in the risk of dying during the follow-up period (p =
      0.002). No alpha-fetoprotein reduction and decrease of the tumor mass was
      observed. CONCLUSIONS: In conclusion, the administration of Sandostatin LAR it
      appears to improve the survival and the quality of life in patients with advanced
      hepatocellular carcinoma.

PMID- 12239915
TI  - Left gastric venous caval direct shunt in esophagogastric varices.
AB  - We undertook 10 cases of Inokuchi shunt operation (left gastric venous caval
      shunt), which is a very logical form of treatment but which is not practiced
      because of its technical difficulty due to the fragility of the left gastric
      vein. The technical procedures were modified to include an ablation and
      anastomosis of the left gastric vein. The difficulty in performing an ablation of
      the left gastric vein from the lymph node and lymphatic duct was solved by using
      surgical loupes. The difficulty in performing an anastomosis was solved by
      dissecting the left gastric vein along with the normal portion of the splenic
      vein, as in Carrel's patch procedure. Although in this study we used an autograft
      of the superficial femoral vein, left renal vein, and right hepatic vein in the
      initial period as well as an original Inokuchi shunt, we also performed direct
      anastomosis by mobilizing the Spiegel lobe by cutting the ligament of the vena
      cava inferior. This device shortened the operation time by 2 hours. All patients
      were discharged without serious complications. All patients were in good
      condition; however, follow-up periods were not very long. In conclusion, the
      Inokuchi shunt operation as well as the distal splenorenal shunt were thought to
      be very useful.

PMID- 12239916
TI  - Focal spared area in fatty liver mimicking a tumor.
AB  - A focal fatty liver change may be associated with several conditions related to
      diffuse hepatic steatosis, such as a diffuse fatty liver change. Using
      ultrasonography, the focal fatty liver change appears more frequently as
      hyperechoic and less frequently as hypoechoic areas in the liver. We report a
      rare case of a focal fatty liver change in which an area was spared in fatty
      liver. The patient was a 42-year-old man. Abdominal ultrasonography showed focal
      hypoechogenicity with an irregular margin in S8 within a bright liver. Abdominal
      computed tomography and enhanced computed tomography showed a high-density mass
      in S8 of the right lobe. A microscopic examination of the specimens from the
      liver biopsy from the hypoechoic region revealed normal hepatic parenchymal
      cells, while tissue samples from the surrounding liver had a high fat deposition.

PMID- 12239917
TI  - Rectal carcinoid tumor successfully treated by endoscopic resection.
AB  - We report a case of rectal carcinoid tumor totally resected by endoscopy. A 48
      year-old male complained of abdominal discomfort. Digital examination revealed a
      slightly hard mass. Colonoscopy demonstrated a slightly hard mass measuring 13 mm
      in diameter in the rectum, 5 cm from the anal verge. Endoscopic resection was
      successfully performed and histological examination led to a diagnosis of
      carcinoid tumor. No local remnant lesion or distant metastasis was found.

PMID- 12239918
TI  - Anastomosis between the middle and right hepatic vein.
AB  - Now, the need for preservation and reconstruction of the middle hepatic vein
      tributaries in the right liver graft without middle hepatic vein or in the
      remnant liver in the donor using left liver graft with middle hepatic vein has
      not been confirmed. Congestion depends on the intrahepatic communicating hepatic
      veins. We report herein the case of a 54-year-old man who had been the donor in a
      living-related liver transplantation and underwent extended left hepatectomy
      including the middle hepatic vein. His remnant right hepatic lobe was drained by
      the right hepatic vein, so the anterior segment was likely to be congested after
      hepatectomy. However, it had not been congested in fact. We observed blood flow
      with an antegrade biphasic waveform, which was "a mirror image of the hepatic
      venous waveform", in the branch of middle hepatic vein in the remnant liver using
      left liver graft with middle hepatic vein. We recognized that the branch of
      middle hepatic vein had functioned as an effective drainage vein. Indeed,
      reconstruction of the middle hepatic vein tributaries was not needed in this
      case. "The mirror image of hepatic venous waveform" is an important sign that
      indicates adequate drainage blood flow.

PMID- 12239919
TI  - Peroral sustained-release indomethacin treatment for rectal adenomas in familial
      adenomatous polyposis: a pilot study.
AB  - BACKGROUND/AIMS: The efficacy of peroral sustained-release indomethacin on rectal
      adenomas in colectomized patients with familial adenomatous polyposis and its
      toxicity were evaluated preliminarily. METHODOLOGY: A total of seven colectomized
      patients with familial adenomatous polyposis were treated with peroral sustained
      release indomethacin at the usual clinical doses. The numbers of rectal polyps
      before and after treatment and approximately one year after cessation of
      treatment were counted using a flexible colonoscope and compared. RESULTS: After
      treatment, reductions of rectal polyp size were observed in all patients. Numbers
      of the rectal polyps also decreased significantly after treatment (median, 1;
      range, 0 to 30) compared with those before treatment (median, 19; range, 4 to 78)
      (P = 0.023). However, Grade 4 anemia due to lower intestinal ulcers occurred in
      two patients. Moreover, one year after termination of the treatment, increase in
      the size and number of rectal polyps was observed in six patients. CONCLUSIONS:
      Because of incomplete efficacy and severe toxicity, general use of this treatment
      for familial adenomatous polyposis patients must be deemed inappropriate.

PMID- 12239920
TI  - Radionuclide colon transit study in patients with idiopathic constipation.
AB  - BACKGROUND/AIMS: Constipation is the most common digestive complaint.
      Radionuclide colon transit study is a useful tool for assessing the motility of
      the colon. In this study, we evaluate patients with idiopathic constipation using
      the radionuclide colon transit study. METHODOLOGY: We studied radionuclide colon
      transit in 23 patients with idiopathic constipation. Thirty healthy volunteers
      were included as a control. RESULTS: Overall, patients with idiopathic
      constipation usually had slow or normal colon transit. CONCLUSIONS: Our study
      suggested that the radionuclide colon transit study may be clinically useful in
      evaluating and assessing the efficacy of therapy in patients with idiopathic
      constipation.

PMID- 12239921
TI  - Mesenteric lymph nodes status influencing survival and recurrence pattern after
      hepatectomy for colorectal liver metastases.
AB  - BACKGROUND/AIMS: We retrospectively reviewed our results with curative hepatic
      resection of metastases from colorectal carcinoma, and analyzed several factors
      of the primary tumor and liver metastases. METHODOLOGY: From 1988 to 1995, 90
      patients underwent curative resection of colorectal liver metastases. The total
      mortality rate was 1.1%. Overall 5-year survival rate after hepatectomy was
      37.9%. RESULTS: Mesenteric lymph node metastases from the primary tumor and the
      prehepatectomy serum carcinoembryonic antigen level were significant. In
      multivariate analysis, positive mesenteric lymph node was an independent
      prognostic factor. In the recurrent patterns, mesenteric lymph node metastases
      were associated with extrahepatic recurrence after hepatectomy. CONCLUSIONS: The
      prehepatectomy carcinoembryonic antigen level and mesenteric lymph node
      metastases of the primary tumor were the most important predictive factors for
      long survival after hepatectomy. Patients with these risk factors should be
      closely followed up with regard not only to the remnant liver but also
      extrahepatic organs.

PMID- 12239922
TI  - Clinical relevance of proliferation biomarkers and p53 expression in rectal
      mucosa and sporadic colonic adenomas: a prospective study.
AB  - BACKGROUND/AIMS: Prospective study to evaluate 1) the pattern of proliferation
      biomarkers and p53 expression in rectal mucosa and adenomatous tissue, and 2) the
      clinical relevance of these biomarkers as predictors for adenoma recurrence.
      METHODOLOGY: 40 patients with sporadic adenomas underwent colonoscopic
      polypectomy and rectal biopsies. Assessment of proliferation biomarkers-
      Ornithine decarboxylase, PCNA and Ki-67--was done in adenomas and rectal mucosa,
      while p53 was performed in adenomas. After polypectomy, 34 adenoma patients were
      followed for 36 months to detect metachronous polyps. 20 controls underwent
      colonoscopy and rectal biopsies, with assessment of proliferation biomarkers.
      RESULTS: Mean values of ornithine decarboxylase, PCNA and Ki-67 in rectal mucosa
      from adenoma patients were not significantly different when compared with the
      control group. The expression of these biomarkers was significantly increased in
      adenomas versus rectal mucosa. Only 6 (15%) out of 40 adenomas were found to
      overexpress p53 protein. During follow-up, recurrent polyps were detected in 12
      patients (relapsing group). Mean values of ornithine decarboxylase, detected at
      index colonoscopy, were not significantly higher in relapsing group versus non
      relapsing group. Mean values of PCNA and Ki-67 detected in adenomas at index
      colonoscopy were significantly higher in relapsing group when compared with non
      relapsing group. Adenoma recurrence was observed in all patients with p53
      overexpression. CONCLUSIONS: Ornithine decarboxylase, PCNA and Ki-67 expression
      in rectal mucosa did not show clinical relevance. Yet, increased expression of
      PCNA or Ki-67 in adenomatous tissue may be a predictor of adenoma recurrence.
      Positive p53 might have the same predictive value.

PMID- 12239923
TI  - New therapeutic strategy of open pelvic fracture associated with rectal injury in
      43 patients over 60 years of age.
AB  - BACKGROUND/AIMS: A diversion of the fecal stream is generally regarded as an
      integral component of minimizing both the infectious morbidity and mortality
      associated with an open pelvic fracture. However, the efficacy of the fecal
      diversion in elderly has yet to be clearly elucidated. We performed a formal
      retrospective comparison between the elderly patients who underwent diversion and
      those who did not. METHODOLOGY: Forty-three consecutive patients who were over 60
      years of age and suffered a pelvic fracture associated with rectal injury. The
      use of fecal diversion was used to delineate the comparison groups: group 1,
      underwent diversion; group 2, did not undergo diversion. The 2 groups were
      compared based on the outcome variables and patient demographics. RESULTS: The
      diverted patients were more severely injured as demonstrated by a higher ISS (p <
      0.05). The length of hospital stay was also significantly greater for the
      diverted patients than for the non-diverted patients (p < 0.05). The number of
      abdominal injuries (p < 0.05) and the number of total diagnoses (p < 0.05) were
      also significantly greater for the diverted patients than for the non-diverted
      patients. There was a significant difference in the distribution of
      intraabdominal fecal contamination (p < 0.05). No significant difference was
      observed in the distribution of fracture stability, fracture patterns, wound
      location, or wound severity between the diverted and non-diverted groups. On the
      other hand, the chi 2 test for trend (Mantel-Haenszel) for fecal diversion and
      the Gustilo grade produced a P value of 0.04. A primary repair with end-colostomy
      was performed in 7 of 23 patients and a resection with an end-colostomy was
      performed in 16 of 23 patients in group 1. On the other hand, a primary repair
      was performed in 3 of 20 patients and a resection with anastomosis was performed
      in 17 of 20 patients in group 2. By the third postoperative month, no significant
      difference was seen in the survival rate: 61% in group I versus 65% in group 2 (P
      = 0.40). By the first postoperative month, the survival rate was significantly
      lower in group 1 than in group 2 (P = 0.04). CONCLUSIONS: Diversion should not be
      regarded as an absolutely safe intervention for open pelvic fracture associated
      with rectal injury. However, if a failure of the primary repair or resection with
      anastomosis once occurs, then the patient's condition could change suddenly or
      worsen. Elderly patients especially have a poor physiological reserve, and thus a
      failure to perform a primary repair or resection with anastomosis can quickly
      lead to patient mortality. There may be some bias when selecting fecal diversion
      or not based on each surgeon's subjective judgment. In our cases, diversions
      tended to be done in severe cases. If surgeons encounter a pelvic fracture with
      severe rectal injury, then aggressive fecal diversion may thus be the procedure
      of choice in emergency elderly cases.

PMID- 12239924
TI  - An experimental assessment of suture techniques using Lapra-ty clips through the
      laparoscope and a case report: laparoscopic closure using Lapra-ty for a
      perforation of the sigmoid colon.
AB  - BACKGROUND/AIMS: As endoscopic procedures become various and complicated, it
      becomes necessary to develop alternative techniques for tissue suture and
      ligation. We have developed a new suture technique intracorporeal knotting.
      METHODOLOGY: An 8-cm suture material having a knot on the other side of a needle,
      was used in laparoscopic surgery. Furthermore, a 5-mm2 Vicryl mesh was pierced as
      a buttress. The Lapra-ty was used to secure the tissue. Under laparotomy, the
      forestomach of a male Donryu rat at 6 weeks of age was incised and sutured with 3
      0 Vicryl. 3-0 Vicryl was secured with the knot substitute (group A) or three
      throw knot (group B) under Nembutal anesthesia. The animals were sacrificed 7
      days after operation. Specimens were taken from the forestomach. Those were fixed
      with 10% formalin and stained with hematoxylin eosin and Elastica Wangieson
      methods. The histological findings were compared between group A and group B. A
      successful laparoscopic closure using Lapra-ty is reported in a patient with a
      perforation of the sigmoid colon. RESULTS: Microscopically, in this method,
      neither erosion, ulcer nor microabscess is evidenced. This method may make an
      intracorporeal knot easy. Also we treated a patient who had a perforation of the
      sigmoid colon using Lapra-ty. The patient recovered without any trouble.
      CONCLUSIONS: This method could make ligation technique much easier and the
      operating time shorter.

PMID- 12239925
TI  - Respiratory function after esophagectomy for patients with esophageal cancer.
AB  - BACKGROUND/AIMS: Postoperative respiratory hypofunction sometime ruins quality of
      life of patients with esophageal cancer. From 1993, we introduced transhiatal
      esophagectomy without thoracotomy as a less invasive surgery to prevent
      postoperative respiratory complications for patients who have relatively early
      stage of esophageal cancer and have preoperative respiratory complication, or who
      are older in age. In this study, postoperative long-term evaluation of
      respiratory functions of patients with esophageal cancer who underwent
      esophagectomy was performed. METHODOLOGY: Among the patients with esophageal
      cancer who underwent esophagectomy in our hospital between 1993 and 1995, we
      selected 13 patients who underwent transhiatal esophagectomy (transhiatal group)
      and 9 patients who underwent transthoracic esophagectomy (transthoracic group).
      Conventional respiratory function tests (VC, vital capacity; FVC, forced vital
      capacity; FEV1, forced expiratory volume in 1 second; FEV1/FVC, ratio of FEV1 to
      FVC; PEF, peak expiratory flow) were compared between the two groups at 3, 6, and
      12 months after operation. RESULTS: In the transhiatal group, postoperative
      average values of VC, FVC, and FEV1 recovered 92%, 98%, and 93% of preoperative
      average values at 6 months after operation, while in the transthoracic group, the
      average values of VC, FVC, and FEV1 were still 78%, 78%, and 72% of preoperative
      average values at 6 months after operation. Postoperative respiratory
      complications were detected in 4 patients (transhiatal: 2 and transthoracic: 2).
      The recovery rates of VC, FVC, FEV1, FEV1/FVC, and PEF at 6 months after
      operation of these 4 patients were not different from those of 18 patients
      without postoperative respiratory complications. CONCLUSIONS: In patients treated
      with transthoracic esophagectomy, postoperative respiratory hypofunctions
      continued over 6 months after surgery. However, postoperative respiratory
      complications may not be related with the long-term postoperative respiratory
      hypofunction in patients with esophageal cancer.

PMID- 12239926
TI  - Endoscopic findings of bleeding esophagogastric varices.
AB  - BACKGROUND/AIMS: Endoscopic findings of bleeding gastric and esophageal varices
      were compared. METHODOLOGY: Seventy patients with first bleeding esophagogastric
      varices without prior treatments were treated: 47 patients had bleeding
      esophageal varices (EV group), 11 patients had bleeding cardiac varices (CV
      group), and 12 patients had bleeding cardiofundic or fundic varices (FV group).
      RESULTS: The red color sign was more common in the EV group (45 patients) than in
      the CV group (4 patients) or FV group (no patients) (P < 0.0001); Mucosal erosion
      over the varices at the site of bleeding was more common in the CV group (9
      patients, P < 0.0005) and FV group (12 patients, P < 0.0001) than in the EV group
      (12 patients). An ulcer at the bleeding point was more common in the CV group (7
      patients, P < 0.01) and FV group (10 patients, P < 0.0001) than in the EV group
      (11 patients). Gastric ulcer was more common in the CV group (7 patients, P <
      0.05) and FV group (10 patients, P < 0.001) than in the EV group (14 patients).
      Erosive gastritis was more frequent in the FV group (12 patients, P < 0.02) than
      in the EV group (30 patients). CONCLUSIONS: Violation of the mucosa barrier
      overlying gastric varices, especially cardiofundic or fundic varices, might be an
      important step leading to variceal hemorrhage.

PMID- 12239927
TI  - Risk factors for esophageal cancer in eastern Anatolia.
AB  - BACKGROUND/AIMS: Epidemiologic studies implicate dietary factors in risk of
      esophageal cancer, particularly in high-incidence areas of the world. In this
      case-control study, 44 patients with esophageal cancer and 100 healthy controls
      were interviewed in the Gastroenterology Department of Teaching Hospital, School
      of Medicine, Ataturk University, Erzurum, Turkey. Eastern Anatolia where the
      study was conducted remains at a crossroads where this particular disease is
      endemic. METHODOLOGY: Questionnaire included education, level of income,
      residence, alcohol and tobacco consumption, eating and drinking habits. The data
      obtained from the patients were compared to those of control cases and analyzed
      using multiple logistic regression, chi 2 and Student's t test. RESULTS: The
      patients' economic level was lower than that of controls. There was no
      association between esophageal cancer and tobacco and alcohol consumption in this
      region. While fruit and vegetable consumption showed a significantly inverse
      association with esophageal cancer. Salt and polyunsaturated fat consumption as
      well as drinking habit of hot tea regionally known as kitlama were positively
      associated with esophageal cancer. CONCLUSIONS: Etiology of esophageal cancer
      shows slight differences in Eastern Anatolia, where esophageal cancer is more
      prevalent than other parts of the country, from that of other parts of the world.
      Drinking of hot tea 'kitlama' and low fruit diet are the most common risk
      factors.

PMID- 12239928
TI  - Ultrasonography of non-perforated appendicitis in young children.
AB  - BACKGROUND/AIMS: The role of ultrasonography in diagnosing non-perforated
      appendicitis in young children is reviewed. METHODOLOGY: Between January 1997 and
      September 1999, three children with abdominal pain due to non-perforated
      appendicitis were admitted to the Nippon Medical School Hospital. Ultrasonography
      of the right lower quadrant was performed using a 7.5-MHz curved array transducer
      with the graded compression technique. RESULTS: Edema of the appendix was
      detected in all cases. The appendiceal diameter was 9 to 18 mm, and the thickness
      of the muscular wall was 3.5 to 6 mm. An echogenic submucosal layer, increased
      periappendiceal echogenicity, and the acoustic shadow of the proximal appendix
      was detected in each case. Localized fluid collection was not observed in any
      patient. Surgical and histopathological findings were nonperforated gangrenous
      appendicitis with fecal stone in all three cases. CONCLUSIONS: Ultrasonography
      provides valuable clinical information about the ileocecal region in children
      with acute abdominal pain. Even when the clinical diagnosis seems well
      established, performing ultrasonography routinely may help reduce the rate of
      perforation by decreasing the time required to establish the diagnosis.

PMID- 12239929
TI  - Helicobacter pylori seroprevalence in Crohn's disease: lack of influence by
      pharmacological treatment.
AB  - BACKGROUND/AIMS: Helicobacter pylori infection has a low prevalence in Crohn's
      disease, possibly because of sulphasalazine therapy. We investigated Helicobacter
      pylori seroprevalence in patients with Crohn's disease never treated with
      sulphasalazine in order to assess the possible role of antibiotic treatment.
      METHODOLOGY: Two groups of patients with Crohn's disease (group I: subjects
      treated with ciprofloxacin, metronidazole or both during the last six months;
      Group II: subjects who were not given antibiotics during the last six months) and
      a control group of 30 patients with irritable bowel syndrome were considered. IgG
      anti-H. pylori levels were measured in all patients. RESULTS: Serology was
      positive respectively in 16.6%, 13.3% and 36.6% of cases in the three groups.
      CONCLUSIONS: Our findings confirm the Helicobacter pylori infection is infrequent
      in Crohn's disease. Neither sulphasalazine nor antibiotics appear to play a role.

PMID- 12239930
TI  - Long-term effect of Helicobacter pylori eradication on quality of life, body mass
      index, and newly developed diseases in Japanese patients with peptic ulcer
      disease.
AB  - BACKGROUND/AIMS: Eradication of Helicobacter pylori is known to reduce ulcer
      recurrence in patients with peptic ulcer disease, however, other long-term
      effects after eradication therapy are not well known. The aim of this study is to
      examine the long-term effect of H. pylori eradication on clinical symptoms,
      quality of life, body mass index, newly emerging symptoms, and newly developed
      diseases. METHODOLOGY: One hundred and ninety-two Japanese patients with peptic
      ulcer disease who received H. pylori eradication therapy at Department of
      Gastroenterology, Osaka City University Hospital between 1993 and 1995 were asked
      to fill in specially a prepared questionnaire. RESULTS: One hundred and fourteen
      patients returned the questionnaires; out of them 98 could be analyzed in this
      study. Successful eradication (n = 88) resulted in alleviation of symptoms,
      improvement of quality of life and increase of body mass index while failure of
      eradication (n = 10) had much less or no effects. A relatively high incidence of
      hyperlipidemia (25.0%) was observed in patients with successful H. pylori
      eradication. Development of hyperlipidemia was associated with significant
      improvement of quality of life especially the item concerning eating and drinking
      habits but not with increased body mass index. In the elderly, no significant
      change in body mass index was observed, however, post-eradication body mass index
      was significantly higher in patients with hyperlipidemia than those without.
      CONCLUSIONS: Cure of H. pylori infection alleviates symptoms and improves quality
      of life of treated patients, but might be associated with an increased incidence
      of hyperlipidemia.

PMID- 12239931
TI  - Results of endotoxin absorption after a subtotal resection of the small intestine
      and a right hemicolectomy for severe superior mesenteric ischemia.
AB  - BACKGROUND/AIMS: The purpose of this study is to analyze the results of endotoxin
      absorption therapy after a subtotal resection of the small intestine and a right
      hemicolectomy for severe superior mesenteric ischemia. METHODOLOGY: From April
      1980 through August 1999, 82 patients with severe superior mesenteric ischemia
      were operated on an emergency basis, and they were divided into two groups. Group
      1 (n = 51), did not undergo postoperative endotoxin absorption therapy, while
      group 2 (n = 31), underwent this therapy. The two groups were compared based on
      the outcome variables. RESULTS: When the number of risk factors was 1 or 2, the
      mortality rate in group 2 was significantly lower than in group 1 (p < 0.05). For
      postoperative lung or liver failure, the mortality rate was significantly higher
      in group 1 than in group 2. For an intraabdominal abscess, the mortality rate was
      significantly higher in group 1 than in group 2. Twenty-two of the thirty-one
      patients in group 2 survived. In the surviving cases, this therapy significantly
      decreased the intravenous concentration of endotoxin (p = 0.04). As for the
      fatalities (n = 9), no significant change in the concentration of endotoxin
      before or after endotoxin absorption was recognized. By the first postoperative
      month, the survival rate was significantly lower in group 1 than in group 2
      (58.8% vs. 71.0%, P = 0.04). CONCLUSIONS: In conclusion, we may now safely say
      that both stoma and a resection are recommended while endotoxin absorption using
      blood filtration may also be an effective additional therapy for post-operative
      septic shock.

PMID- 12239932
TI  - Treatment of superior mesenteric artery embolism with a fibrinolytic agent: case
      report and literature review.
AB  - Successful treatment of superior mesenteric artery embolism depends on an
      aggressive approach in patients at risk for mesenteric ischemia. This approach
      favors an early diagnosis and permits the reestablishment of arterial flow within
      an appropriate time, with prevention of vasospasm and control of organic
      insufficiencies. We report here a case of superior mesenteric artery embolism in
      which arterial flow was reestablished by selective intra-arterial infusion of
      streptokinase. The literature has reported 18 similar cases thus far. This
      procedure could be an alternative to embolectomy in selected patients, i.e.,
      patients with an early diagnosis, no evidence of intestinal necrosis and with
      partial occlusion and/or occlusion of secondary branches of the superior
      mesenteric artery. Frequent arteriographies and intensive care are necessary in
      this approach. The patient should be continuously monitored because of the
      possibility of treatment failure and the need for embolectomy.

PMID- 12239933
TI  - Malignant gastrointestinal stromal tumor of the jejunum with liver metastasis.
AB  - Primary malignant tumors of the small intestine are rare. Malignant
      gastrointestinal stromal tumors are the third most common neoplasm among primary
      malignant small bowel tumors. A 56-year-old woman was admitted to our hospital
      because of appetite loss and dyspnea with movement. On admission, physical
      examination revealed severe anemia in her conjunctiva and a tumor in her left
      abdomen. Her hemoglobin level was 6.2 g/dL and other laboratory data were normal.
      Abdominal ultrasonograms and computed tomograms revealed a 55 x 70-mm
      heterogeneous mass and multiple low-density masses in the liver. Superior
      mesenteric arteriograms revealed a hypervascular tumor fed by the jejunal
      arteries. A malignant gastrointestinal stromal tumor arising from the jejunum
      with liver metastases was suspected. Partial resection of the affected jejunum
      and left trisegmentectomy of the liver were performed. The resected primary tumor
      was 120 x 45 x 65 mm. The tumor was mainly submucosal, but extended outside the
      jejunum; it was elastically firm and multiloculated. A small ulcer was seen on
      the mucosal side. The metastatic liver tumors were solid or cystic with diameters
      of 20 to 40 mm. Histopathological examination revealed that the tumors were
      characterized by fascicular proliferation of spindle-shaped cells.
      Immunohistochemical staining was positive for CD34 and c-kit, and negative for S
      100 protein and smooth muscle actin. This case was a malignant gastrointestinal
      stromal tumor originating in the jejunum with liver metastases. The primary tumor
      and liver metastases were successfully resected simultaneously.

PMID- 12239934
TI  - Clinical characteristics and prognosis of hepatocellular carcinoma patients with
      paraneoplastic syndromes.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma patients with paraneoplastic syndromes
      usually have a larger tumor volume and a higher serum alpha-fetoprotein. Whether
      the presence of paraneoplastic syndromes, such as hypercholesterolemia,
      hypoglycemia, hypercalcemia, and erythrocytosis in hepatocellular carcinoma
      patients is a significant prognostic factor in patients' survival is of clinical
      interest. METHODOLOGY: We evaluated the occurrence of paraneoplastic syndromes in
      903 hepatocellular carcinoma patients; 179 (20%) patients developed
      paraneoplastic syndromes either upon diagnosis or during follow-up, 179 age-sex
      tumor volume-matched hepatocellular carcinoma patients without paraneoplastic
      syndromes were selected as controls. Serum liver biochemistry, alpha-fetoprotein,
      clinical Child-Pugh's score, tumor image studies, histological features,
      accessibility to treatment, and survival were recorded and compared between
      patients with and without paraneoplastic syndromes. Prognostic factors in
      patients' survival were analyzed. The clinical course and survival of
      hepatocellular carcinoma patients with different paraneoplastic syndromes were
      also compared. RESULTS: Multivariate Cox regression analysis revealed Child
      Pugh's grade C, ineligibility for active treatment, serum alpha-fetoprotein >
      10,000 ng/mL, main portal vein tumor thrombosis, and the presence of
      paraneoplastic syndromes were all independent unfavorable prognostic factors for
      survival. The median survival from the occurrence of paraneoplastic manifestation
      to death was only 36 days. Patients with different paraneoplastic syndromes had
      similar clinical characteristics in Child-Pugh's score, serum alpha-fetoprotein
      level, tumor volume, prevalence of main portal vein tumor thrombosis, and
      accessibility for active treatment upon diagnosis. However, erythrocytosis and
      hypercholesterolemia usually developed earlier in the clinical course, whilst
      hypoglycemia and hypercalcemia were usually terminal events. Hepatocellular
      carcinoma patients with erythrocytosis tended to have a longer survival than
      patients with other paraneoplastic syndromes. CONCLUSIONS: The presence of
      paraneoplastic syndromes in hepatocellular carcinoma patients is an unfavorable
      prognostic factor, excluding the occurrence of erythrocytosis.

PMID- 12239935
TI  - Efficacy of chronic hepatitis C therapy with interferon alpha (IFN-alpha) in
      Slovenia.
AB  - BACKGROUND/AIMS: Eighty Slovene patients with chronic hepatitis C were included
      in a prospective study conducted in the period 1997-1998 with the purpose to
      establish the efficacy of interferon alpha therapy. The average age of the
      patients was 39 years. In more than half of the patients (52%) the mode and time
      of onset of the infection were unknown. Two thirds of the patients were males.
      The plasma viral load exceeded 2 x 10(6) copies/mL in only three patients and in
      more than half of the cases (54%) HCV genotype 1b was present. METHODOLOGY: The
      18-month treatment with 3 MU interferon alpha three times a week was concluded in
      53 patients and, after doubling the initial dose of interferon alpha from 3 MU to
      6 MU, in 5 patients. In 11 patients, the treatment was discontinued prematurely,
      after six months, due to therapeutic failure (despite doubling the initial dose
      of interferon alpha Eleven patients withdrew from the treatment: six of them due
      to side effects and five due to personal reasons. RESULTS: Complete response to
      therapy with disappearance of HCV from the blood was observed in 34 patients
      (49%), while in 24 the response to therapy was partial, i.e., the biochemical
      tests showed normalization of values but viremia persisted. There was a
      significant relation between the therapeutic response and those patients with the
      genotype 3 (p = 0.01). After three months of follow-up, complete therapeutic
      response was still observed in 19 patients (28%), most of them with genotype 3.
      Despite persistent viremia there was no progression of liver inflammation in
      eight partial responders, as evidenced by liver rebiopsy. Thus, it was confirmed
      that treatment is justified in these patients. CONCLUSIONS: During the
      continuation of the follow-up period we shall record further course of the
      disease and make an attempt in a subsequent study to improve the efficacy of the
      treatment by introducing a combination of interferon alpha and ribavirin into
      therapy.

PMID- 12239936
TI  - Should intraoperative ultrasonography be used routinely in hepatic hydatidosis?
AB  - BACKGROUND/AIMS: Recurrent or secondary hydatidosis are the most important
      problems of hepatic hydatidosis in the late postoperative period. The spread of
      cystic liquid, overlooked centrally located or pericystic satellite cysts that
      are inconspicuous during operation are the basic reasons for the problem.
      METHODOLOGY: In order to prevent the risk of recurrent or secondary hydatidosis,
      22 liver hydatid cystic patients were taken for a prospective study. Beyond the
      routine investigations and researches, after the completion of conventional
      surgical procedures, intraoperative ultrasonography was applied to all patients.
      RESULTS: In three patients the existence of cysts were not found by conventional
      research (13.63%), in another patient (4.54%) cysto-biliary communication which
      had been determined clinically but was invisible due to difficulty in anatomic
      localization was verified by means of intraoperative ultrasonography.
      CONCLUSIONS: Intraoperative ultrasonography has been thought to be beneficial to
      find centrally localized cysts which may be inconspicuous especially in cases of
      multiple cysts.

PMID- 12239937
TI  - Tolerance to intermittent ischemia of damaged rat liver by thioacetamide.
AB  - BACKGROUND/AIMS: Tolerance of damaged rat livers for intermittent ischemia was
      assessed. Clinically, tolerance of operative ischemia by diseased livers, long
      thought minimal, is being reexamined. METHODOLOGY: A rat model using 0.04%
      thioacetamide-induced liver damage followed by pedicle occlusion was used to
      study partial hepatic ischemia in injured livers in terms of survival, hepatic
      tissue blood flow, beta-ATP content, liver enzymes and histology. Prior to
      continuous ischemia (150 min) or intermittent ischemia (alternating every 15 min
      with reperfusion for 10 cycles) animals were divided into mild (B) and severe (A)
      thioacetamide-induced injury groups according to the hepatic clearance rate of
      indocyanine green from plasma. RESULTS: The survival rates for 1 week after
      intermittent ischemia were 43%, 77%, and 93% in groups A and B and in controls
      (group C), respectively. No group A or B animals receiving continuous ischemia
      survived. Hepatic tissue blood flow and liver beta-ATP levels in serum were
      significantly higher in group A than in other groups. Marked damage also was
      observed histologically in group A. CONCLUSIONS: Intermittent liver circulation
      blockage may be relatively safe in a damaged liver, but a more severe degree of
      damage predisposes to serious ischemia-reperfusion injury.

PMID- 12239938
TI  - Hemostatic modulation with the liver dialysis device in humans with advanced
      liver disease.
AB  - BACKGROUND/AIMS: To determine the alterations in coagulation and fibrinolysis
      occurring in patients treated with the liver dialysis device. METHODOLOGY:
      Patients with advanced liver disease treated with the liver dialysis device were
      studied immediately before and after the liver dialysis device treatment.
      SETTING: A university hospital intensive care unit. PATIENTS: Thirteen
      consecutive patients with advanced liver disease being evaluated for or awaiting
      liver transplantation. INTERVENTION: 4-6 hours of liver dialysis treatment for
      management of hepatic encephalopathy. OUTCOME MEASURES: A panel of coagulation
      and anticoagulation factors, as well as fibrinolytic and anti-fibrinolytic
      factors plus measures of activation of inflammation and soluble adhesion factors.
      RESULTS: The liver dialysis device used was found to be associated with
      activation of both coagulation and fibrinolytic pathways, activation of
      inflammation reactants, and an increase in sL-selectin levels. CONCLUSIONS: Liver
      dialysis device activates both coagulant and fibrinolytic pathways, activates
      inflammatory response, but these responses are limited to the vascular
      compartment by an increase in sL-selectin levels.

PMID- 12239939
TI  - Primary and secondary liver endocrine tumors: clinical presentation, surgical
      approach and outcome.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the role of surgical
      treatment in the management of primary and secondary liver endocrine tumors.
      METHODOLOGY: We reviewed our experience of surgical treatment for primary and
      secondary liver endocrine tumors in 34 patients from 1980 to 1999. There were 31
      cases of liver metastases from distant primary endocrine tumors treated by
      curative resection in 11 patients, cytoreductive surgery in 15 and orthotopic
      liver transplantation in 5. The remaining 3 consisted of primary liver endocrine
      tumor in 2 patients, liver invasion from primary bile duct endocrine tumor in 1,
      and all of them were treated by curative liver resection. RESULTS: In patients
      with distant primary endocrine tumors, the actuarial 5-year survival after
      curative liver resection, cytoreductive surgery, and orthotopic liver
      transplantation was of 91%, 50% (being 90% for non-functioning tumors), and 60%,
      respectively. In patients with primary liver endocrine tumors, long-term survival
      and disease-free survival (52-240 months) was achieved after curative resection.
      CONCLUSIONS: When indicated, liver surgery can offer cure and/or improve survival
      in patients with primary or secondary liver endocrine tumors. The choice of the
      surgical modality should be evaluated carefully.

PMID- 12239940
TI  - Effect of angiotensin-converting enzyme inhibitors on liver regeneration in rats.
AB  - BACKGROUND/AIMS: We previously reported that bradykinin augments liver
      regeneration in rats. The angiotensin-converting enzyme is also a powerful
      bradykinin-degrading enzyme. METHODOLOGY: Adult rats received lisinopril,
      captopril, enalaprilat, or saline solution, intraperitoneally, for 5 days before
      70% partial hepatectomy, and daily after surgery. They received also losartan and
      bradykinin. Rats were sacrificed at 12, 24, 36, 48, 72, and 120 hours after
      hepatectomy. Liver regeneration was evaluated in terms of the restoration of
      liver weight in proportion to body weight, liver DNA content and immunostaining
      for proliferating cell nuclear antigen. RESULTS: The proliferating cell nuclear
      antigen labeling index was higher in the lisinopril-treated group than in the
      control group at all time points after hepatectomy, except 120 hours. The remnant
      liver dry weight was higher in lisinopril-treated rats than in control rats at
      early time points after surgery. The liver DNA content was higher in three
      angiotensin-converting enzyme inhibitor-treated groups than in the control group
      at 36 hours after hepatectomy. The bradykinin-induced regenerative response was
      similar to the lisinopril-induced response, and losartan induced a lower
      hepatocyte labeling index in comparison to the control group at 36 hours after
      hepatectomy. CONCLUSIONS: The present results provide evidence that angiotensin
      converting enzyme inhibitors remarkably enhance liver regeneration.

PMID- 12239941
TI  - Detection of precore-mutant hepatitis B virus genome in patients with acute and
      fulminant hepatitis using mutation site-specific assay (MSSA).
AB  - BACKGROUND/AIMS: Precore mutation of hepatitis B virus was recently been
      suggested to be involved in the pathogenesis of fulminant hepatitis. In this
      study, we analyzed the occurrence of precore mutants in patients with acute and
      fulminant hepatitis B using new simple rapid and sensitive MSSA (mutation site
      specific assay) and evaluated this method for predicting prognosis. METHODOLOGY:
      We analyzed HBV-DNA of 10 patients with fulminant hepatitis B, 15 patients with
      acute self-limited hepatitis, and 4 patients with acute severe hepatitis using
      MSSA. Precore point mutation (G to A; 83rd base of precore region) was examined
      using a mutation-trapped oligonucleotide primer, which would yield a polymerase
      chain reaction amplification product only with precore mutants. RESULTS: We
      distinguished precore mutants from wild type according to the presence or absence
      of the band at 203 bp, which was amplified in only precore mutants by polymerase
      chain reaction. Mutation of the precore region was observed in all 10 patients
      with fulminant hepatitis, in 3 of the 4 patients with severe hepatitis, and 11 of
      15 patients with self-limited hepatitis. Negative pre-C mutants in patients with
      HBeAg indicates good prognosis of hepatitis. CONCLUSIONS: Precore mutant strains
      of HBV-DNA play an important role but are not specific for fulminant hepatitis,
      and the mere presence of precore mutants may not directly lead to fulminant
      hepatitis or severe hepatitis. However, this method is useful for predicting
      outcome of patients with acute HBV hepatitis, especially in HBeAg-positive state.

PMID- 12239943
TI  - Hepatic resection for hepatocellular carcinoma existing with liver cirrhosis.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma is usually complicated with liver
      cirrhosis, which makes its treatment difficult. Also a high rate of recurrence
      exists after surgical resection. However, how the prognosis after surgical
      treatment is affected by the severity of coexisting cirrhosis has not been
      clarified. METHODOLOGY: We compared the postoperative longterm courses of
      hepatocellular carcinoma patients with cirrhosis according to the liver function.
      All 112 hepatocellular carcinoma patients in this study underwent curative
      hepatic resection, and were classified into three groups according to the
      severity of liver dysfunction. The ICG R15' (indocyanine green retention test)
      normal: < 10%) was used in this study. Patients whose ICG R15' was less than 20%
      were classified as group I of 62, patients equal to 20% or between 20% and 30% as
      group II of 24, and patients equal to and more than 30% as group III of 26.
      RESULTS: In this series, 76 of 112 patients had recurrence (68%). A second
      hepatic resection was performed in six cases of group I and one case in group II.
      Fifty-eight of 76 recurrent cases (76%) were treated with transcatheter arterial
      chemoembolization. A total of eleven cases had no transcatheter arterial
      chemoembolization in the three groups: 3 cases in group I, 5 cases in group II,
      and 3 cases in group III; The three cases of group III had no treatment because
      of extremely poor liver dysfunction, whilst the 8 patients without transcatheter
      arterial chemoembolization in groups I and II had hepatocellular carcinoma itself
      and other diseases. The 1-, 3-, and 5-year survival rates after recurrence were
      92%, 48%, and 14%, respectively, in group I; 83%, 37%, 12%, respectively, in
      group II; and 66%, 30%, 0%, respectively, in group III. The prognosis was
      significantly worse according to the degree of liver dysfunction (p = 0.0206).
      CONCLUSIONS: The prognosis of hepatocellular carcinoma with liver cirrhosis is
      affected not only by hepatocellular carcinoma itself, but also by the severity of
      the coexisting cirrhosis. Moreover, the cirrhotic liver can decline due to
      surgery. Surgical resection of this disease should be performed after careful
      patient selection and using a less invasive technique.

PMID- 12239942
TI  - Effects of 5-isosorbide mononitrate and propranolol on subclinical hepatic
      encephalopathy and renal function in patients with liver cirrhosis.
AB  - BACKGROUND/AIMS: In patients with cirrhosis pharmacological treatment of portal
      hypertension using beta-blockers and vasodilators has raised concerns for its
      potential deleterious effects on renal function and encephalopathy. To clarify
      this issue we evaluated the effects of propranolol and 5-isosorbide mononitrate
      or both on subclinical hepatic encephalopathy and renal function in a prospective
      randomized double-blinded study. METHODOLOGY: Thirty patients Child-Pugh A or B,
      with esophageal varices, normal renal function and non-previous pharmacological
      treatment were studied. After a basal period, patients received during 4 weeks 5
      isosorbide mononitrate (80 mg/day) or placebo. In the next 4 weeks, propranolol
      was added to both groups. At baseline and at the end of each study period we
      assessed: renal function tests; plasma renin activity and aldosterone;
      subclinical hepatic encephalopathy (electroencephalograms, visual evoked
      potentials and psychometric studies). Mean arterial pressure, cardiac output
      (echo-Doppler) and indocyanine green retention were also measured. RESULTS: The
      most common alterations at baseline were increased arterial ammonia levels (85%),
      abnormal indocyanine green retention (75%), abnormal trail making B (44%),
      decreased inulin clearance (30%) and high plasma renin activity (27%). After 4
      weeks of 5-isosorbide mononitrate or placebo no significant changes were observed
      in any variable. Five out of 14 patients receiving 5-isosorbide mononitrate were
      withdrawn due to side effects. The addition of propranolol decreased
      significantly plasma renin activity in both groups and cardiac output in those
      receiving 5-isosorbide mononitrate but did not change other variables.
      CONCLUSIONS: In patients with compensated or slightly decompensated liver
      cirrhosis 5-isosorbide mononitrate, propranolol or the association of both did
      not produce detectable worsening of subclinical hepatic encephalopathy or renal
      function.

PMID- 12239944
TI  - Plasma tissue inhibitor of metalloproteinases-1 and transforming growth factor
      beta 1--possible non-invasive biomarkers of hepatic fibrosis in patients with
      chronic B and C hepatitis.
AB  - BACKGROUND/AIMS: The role of transforming growth factor-beta 1 (TGF-beta 1) in
      liver fibrosis is in part related to impairment of extracellular matrix breakdown
      by stimulation of tissue inhibitor of metalloproteinases-1 (TIMP-1) gene. The aim
      of the study was to evaluate association between TGF-beta 1 and TIMP-1 in
      relation to liver injury in chronic viral hepatitis B and C. METHODOLOGY:
      Association between plasma TGF-beta 1 and TIMP-1 was evaluated in 28 consecutive
      patients undergoing liver biopsy for chronic viral hepatitis B and C (CH-B, CH-C)
      and these tests were correlated with hepatic fibrosis, inflammation and liver
      function tests. Moreover carboxyterminal cross-linked telopeptide of type 1
      procollagen (ICTP) and carboxyterminal propeptide of type 1 collagen (PICP) were
      also measured for assessment of extracellular matrix breakdown or synthesis,
      respectively. RESULTS: Chronic viral hepatitis B and C resulted in a significant
      increase in plasma TIMP-1 levels but not TGF-beta 1. Among biochemical markers of
      liver injury, significant correlation with TGF-beta 1 and TIMP-1 was demonstrated
      in respect to aminotransferase activities in both groups. TIMP-1 showed
      significant correlation with ICTP levels in both CH-B (r = 0.59) and CH-C (r =
      0.62), whereas TGF-beta 1 was correlated with ICTP only in CH-C patients (r =
      0.75). PICP did not demonstrate any correlation with either TGF-beta 1 or TIMP-1.
      Hepatic fibrosis, but not inflammation, correlated significantly with TGF-beta 1
      (CH-B: r = 0.73; CH-C: r = 0.79) and TIMP-1 (CH-B: r = 0.66; CH-C: r = 0.71) in
      both groups and there was a significant correlation between TIMP-1 and TGF-beta 1
      in the CH-B group (r = 0.83) and CH-C group (r = 79). CONCLUSIONS: These results
      support the role of TIMP-1 in a TGF-beta 1-dependent mechanism for liver fibrosis
      and suggest their plasma levels can be used as a possible early non-invasive
      marker of liver fibrosis useful for chronic hepatitis management.

PMID- 12239945
TI  - Interferon treatment for patients with chronic hepatitis C infected with high
      viral load of genotype 2 virus.
AB  - BACKGROUND/AIMS: Interferon treatment is more effective in patients with chronic
      hepatitis C infected with genotype 2a virus than those with genotype 1b virus. We
      analyzed patients with chronic hepatitis C treated by interferon in our clinics
      to develop a more effective regimen of interferon treatment for patients with
      genotype 2 virus infection. METHODOLOGY: We retrospectively analyzed the
      virological response of 36 patients with chronic hepatitis C with a high viral
      load, including 28 cases infected with the genotype 2a virus and 8 cases with the
      genotype 2b virus. The serum viral load of these patients were 6.0 log copies/mL
      and higher by the competitive polymerase chain reaction assay method. All
      patients could be treated with interferon-alpha or -beta for 6 months. Eleven
      patients were administered 6 million units of interferon-beta once daily for 6
      weeks and then thrice weekly (group A). Twelve patients were administered 6
      million units of interferon-alpha daily initially for 2 weeks and then thrice
      weekly (group B), and 10 patients were treated with the same dose of interferon
      alpha thrice weekly from the first administration (group C). We decided the
      criteria of complete remission as the absence of serum HCV-RNA at both points of
      the end of interferon treatment and 6 months later. RESULTS: For all patients
      with genotype 2a virus infection, the complete remission, transient response and
      no response rates were 46.4%, 39.3% and 14.3%, respectively. The complete
      remission rates in group A, B and C were 100%, 41.7% and 20%, respectively. The
      transient remission rates in group B and C were 41.7% and 60%, respectively. The
      no response rates in group B and C were 16.7% and 20%, respectively. All patients
      with a high viral load of genotype 2a virus showed eradicated serum HCV-RNA virus
      in group A. The eradication rate of serum HCV-RNA in patients infected with the
      genotype 2a virus in group A was significantly higher than that of group B (p <
      0.02) or group C (p < 0.01). For all patients with genotype 2b virus infection,
      complete remission, transient remission and no response rates were 12.5%, 50.0%
      and 37.5%, respectively. The complete remission rate of patients with the
      genotype 2b virus in group A and group B plus C was 0% and 25.0%, respectively.
      The eradication rate of patients with the genotype 2a virus in group A was
      significantly higher than that of patients with the genotype 2b virus (p < 0.01).
      CONCLUSIONS: These findings suggest that the initial sufficient dose of
      interferon administration is effective to eradicate serum HCV-RNA in patients
      with a high viral load of genotype 2a virus in chronic hepatitis C.

PMID- 12239946
TI  - Hepatic focal nodular hyperplasia: the "star sign" on gadolinium-enhanced
      magnetic resonance angiography.
AB  - BACKGROUND/AIMS: This study aimed at presenting the three-dimensional gadolinium
      enhanced magnetic resonance angiography findings of hepatic focal nodular
      hyperplasia with angiographic correlation. METHODOLOGY: Three patients (one had
      abdominal pain, two were asymptomatic) with liver mass or nodules in the liver
      revealed on ultrasound underwent three-dimensional gadolinium-enhanced magnetic
      resonance angiography. Catheter angiography was available for correlation in all
      three cases. Other imaging studies including conventional magnetic resonance
      imaging in three patients, computed tomography in two and scintigraphy scan in
      one were reviewed. Surgical resection and biopsy were performed in one and two
      patients respectively. RESULTS: The ultrasound, computed tomography, magnetic
      resonance and scintigraphy findings were non-specific for focal nodular
      hyperplasia in all three patients. However, gadolinium-enhanced magnetic
      resonance angiography demonstrated tumor vessels radiating from its center to the
      periphery, which corresponded to the spokes of the characteristic "spoke-wheel"
      pattern on catheter angiography, producing the so called "star sign," that may
      suggest the diagnosis of focal nodular hyperplasia. Histopathologic examinations
      revealed focal nodular hyperplasia. CONCLUSIONS: This report highlights the
      usefulness of gadolinium-enhanced magnetic resonance angiography in the diagnosis
      of hepatic focal nodular hyperplasia by demonstrating the "star sign" and that
      computed tomography, scintigraphy, and catheter angiography may thus be obviated
      in such instances.

PMID- 12239947
TI  - Serum thrombopoietin in chronic liver disease: relation to severity of the
      disease and spleen size.
AB  - BACKGROUND/AIMS: Thrombopoietin is a thrombopoietic factor mainly synthesized in
      the liver. Its production is regulated by the mass of megakaryocytes and
      platelets. Impaired production of thrombopoietin may be responsible for
      thrombocytopenia in chronic liver disease. METHODOLOGY: We studied thrombopoietin
      serum concentration in 68 patients with chronic liver disease of various degrees
      (39 with thrombocytopenia), in 5 patients with thrombocytopenia due to
      hematological disease, and in 27 healthy controls. RESULTS: Thrombopoietin
      concentration was higher in patients with liver disease than in controls.
      Patients with hematological disease had much higher thrombopoietin concentration
      than patients with liver disease. Among patients with liver disease and
      thrombocytopenia, thrombopoietin concentration was higher in cirrhosis than in
      chronic hepatitis. A negative correlation was found between platelet counts and
      spleen size and between thrombopoietin concentration and spleen size. No
      correlation was found between thrombopoietin concentration and liver disease
      severity. CONCLUSIONS: Patients with liver disease and thrombocytopenia have
      serum thrombopoietin concentration higher than normal controls. It seems
      therefore that the liver, even seriously diseased, maintains the ability to
      produce thrombopoietin. In the liver patients the number of circulating platelets
      and the serum levels of thrombopoietin are inversely correlated with the size of
      the spleen suggesting that thrombopoietin, although normally produced, might be
      turned over in platelets sequestrated in the spleen.

PMID- 12239948
TI  - Cellular interpretation of hepatocellular carcinoma by using cell blocks
      technique.
AB  - BACKGROUND/AIMS: The purpose of this study was to investigate the cellular
      interpretation of hepatocellular carcinoma in specimens obtained by needle
      aspiration with preparation of cell blocks. METHODOLOGY: We consecutively
      collected 58 patients who were histologically proved to have hepatocellular
      carcinoma. Corresponding to the size of hepatocellular carcinoma, the cellular
      dysplasia of specimens obtained by both aspirations with cell blocks and
      conventional liver biopsy from each hepatocellular carcinoma was investigated
      according to Edmondson-Steiner 's grading (Gr). RESULTS: Of 16 small
      hepatocellular carcinomas (diameter < 3.0 cm), the occurrence rate of dysplasic
      grading of Gr-I, Gr-II, Gr-III and Gr-IV was 31.3%, 43.8%, 18.8% and 6.3% in
      aspiration with cell blocks, and 46.2%, 38.5%, 15.4% and 0.0% in liver biopsy
      respectively. There was no Gr-I of cellular dysplasia in the 15 moderate size
      (3.1-6.0 cm) and 27 large size (> 6.1 cm) hepatocellular carcinomas. The
      occurrence rate of Gr-III cellular dysplasia in small hepatocellular carcinoma
      was lower than that in large hepatocellular carcinoma (18.8% vs. 55.6%, p =
      0.019). The larger the tumor is, the more poorly differentiated it became. Four
      of six histologic false-negative hepatocellular carcinoma in aspiration with cell
      blocks were large size hepatocellular carcinoma (> 6.5 cm in diameter) with
      necrosis. CONCLUSIONS: These results suggest that the interpretation of the cell
      grading of hepatocellular carcinoma by aspiration with cell blocks is not
      inferior to that by conventional liver biopsy. This technique seems to provide
      another route to study the cellular dysplasia of hepatocellular carcinoma in
      living patients even to follow-up their treatment response.

PMID- 12239949
TI  - Comparative evaluation of three commercial assays for quantitative measurement of
      hepatitis B virus DNA in serum samples.
AB  - BACKGROUND/AIMS: Quantitative determination of HBV DNA in serum samples is
      indispensable for predicting disease progression and for monitoring the antiviral
      treatment in patients with chronic HBV infection. METHODOLOGY: Three commercial
      assays for quantification of HBV DNA: Digene Hybrid-Capture HBV DNA Assay, Bayer
      Quantiplex HBV DNA Assay and Roche Amplicor HBV Monitor Test were comparatively
      evaluated under the routine conditions of diagnostic virology laboratory, using
      61 serum samples obtained from 55 Slovenian patients with chronic hepatitis B.
      RESULTS: HBV DNA was detected by Amplicor, Quantiplex and Hybrid-Capture in 38
      (62.3%), 34 (55.7%) and 27 (44.3%) samples, respectively. The sensitivity of
      Amplicor and Quantiplex assays did not differ significantly (p = 0.13), while
      both Amplicor and Quantiplex assays were found to be significantly more sensitive
      than Hybrid-Capture (p = 0.003 and p = 0.02, respectively). For a given sample,
      the highest correlation was observed between HBV DNA loads determined by
      Quantiplex and Hybrid-Capture assays (r = 0.85, p < 0.0001). CONCLUSIONS:
      Amplicor HBV Monitor Test seems to be the most sensitive assay for the detection
      of HBV DNA in serum samples and can be clinically used for monitoring patients
      with chronic HBV infection.

PMID- 12239950
TI  - Changing typology of brain death liver donors: characteristics and impact of risk
      factors on short-term outcome.
AB  - BACKGROUND/AIMS: An effective recruitment plan and the use of donors with risk
      factors are essential means of compensating for the lack of organs, but mean a
      significant change in the type of donor. This study defines the characteristics
      of the donors currently used, evaluates their impact on short-term outcome and
      underlines the need for a different approach to organ selection. METHODOLOGY:
      Data concerning 244 patients were collected for the study of donor
      characteristics by age groups, and the multivariate analysis of the associated
      risk factors. RESULTS: There were no significant differences other than the cause
      of donor death and the appearance of the organ. The annual percentage of donors
      aged more than 60 years has increased from 5.2% to 47.6%; the percentage of
      organs from over-60-year-old donors discarded after bioptic sampling was 25.6%
      (10.4% for donors aged < 60 years). Perioperative mortality did not significantly
      differ on the basis of donor age (p = 0.186). CONCLUSIONS: Today's liver donors
      are mainly subjects who have died of cerebrovascular disease, often at an age of
      > 60 years, and are also affected by other diseases or metabolic alterations.
      They require a different method of evaluation and, in those aged more than 60
      years, the routine use of histological examinations in organ selection.
      Furthermore, the judicious extension of the inclusion criteria and the
      characteristics of the currently available donors do not seem to affect short
      term, post-transplant outcome.

PMID- 12239951
TI  - Anterior approach for resection of metastatic liver tumors infiltrating the
      caudate lobe.
AB  - A 57-year-old woman with a cecal cancer underwent a curative, right
      hemicolectomy. One year after the operation, she was noted to have liver
      metastases with two focuses. One was 12 cm in diameter and was located mainly at
      the medial hepatic segment and infiltrating into the caudate lobe. The inferior
      vena cava and major hepatic vein were compressed and/or involved with the tumor.
      The patient underwent an extended left lobectomy using an anterior approach,
      which gave us sufficient visualization. The patient remains healthy 4 years after
      the operation. Hepatectomy using an anterior approach may be useful for expanding
      the surgical indications for metastatic disease.

PMID- 12239952
TI  - Preoperative selective portal vein embolization (PSPVE) before major hepatic
      resection. Effectiveness of Doppler estimation of hepatic blood flow to predict
      the hypertrophy rate of non-embolized liver segments.
AB  - Hepatocellular carcinoma may be unresectable for volumetric reasons. The future
      remaining liver after hepatectomy might be too small to ensure survival.
      Preoperative selective portal vein embolization of the tumorous lobe can induce
      hypertrophy of the future remaining liver and enable safer surgery. A 76-year-old
      patient with hepatocellular carcinoma needed right lobectomy however, the future
      remaining liver was judged insufficient to ensure an uneventful postoperative
      course. The left lobe to whole liver volumetric ratio was to small (29.7%) and a
      preoperative selective portal vein embolization of the right portal branch via a
      percutaneous, transhepatic, contralateral approach was performed without side
      effects. A Doppler estimation of left branch portal blood flow and velocity was
      carried out before and after preoperative selective portal vein embolization.
      After 21 days the left lobe volume increased by about 44.2% with a safe left
      lobe/whole liver ratio of 40.8%. The portal blood flow and portal blood flow
      velocity showed an increase of 253% and 122%, respectively. A right lobectomy was
      performed without complications. Three months later, computed tomography scan
      showed no hepatocellular carcinoma recurrence. Preoperative selective portal vein
      embolization is a safe technique which can enable major hepatectomy to be
      performed in situations otherwise judged unresectable for a life-threatening
      volumetric insufficiency. The portal blood flow and portal blood flow velocity
      evaluations can easily predict the hypertrophy rate of non-embolized liver
      segments.

PMID- 12239953
TI  - A case of primary non-function following adult-to-adult living donor liver
      transplantation.
AB  - We report a case of primary non-function of graft liver following adult-to-adult
      living donor liver transplantation. The recipient was a 43-year-old male with
      hepatitis B-associated liver cirrhosis. The donor was a 28-year-old brother of
      the recipient. We transplanted a left lobe graft from the donor weighing 550 g,
      in which 20% macrovesicular steatosis was observed. Total ischemic time was less
      than 40 minutes. The recipient presented a marked impairment of coagulation
      profile and marked elevation of liver enzymes without any evidence of flow
      disturbance of the liver vessels, which was very similar to the clinical course
      of primary non-function following cadaveric donor liver transplantation. We
      performed retransplantation using a cadaveric whole liver graft on the second day
      after the initial operation and the recipient survived without any complications.
      A resected graft liver specimen showed total necrosis of hepatocytes without
      intravascular thrombosis. We concluded that failure of the living donor graft was
      due to primary non-function occurring in the adult recipient.

PMID- 12239954
TI  - Hemoperitoneum secondary to spontaneous rupture of metastatic epidermoid
      carcinoma of liver: case report and review of the literature.
AB  - Massive hemoperitoneum due to spontaneous rupture of liver metastasis is
      remarkably rare. This is of interest because ruptured hepatocellular carcinoma is
      the most common cause of fatal hemoperitoneum in the Far East. We describe a case
      of hemoperitoneum secondary to spontaneous rupture of metastatic epidermoid
      carcinoma of liver. A 60-year-old man with chronic hepatitis C suffered from
      sudden onset of abdominal pain and pallid face with a tentative diagnosis of
      hepatocellular carcinoma with rupture. Tumor growth with rupture was suspected
      based on dynamic computed tomography, but the angiography could not demonstrate
      the tumor lesion. We diagnosed that the tumor was a metastatic epidermoid
      carcinoma, of unknown origin, based on the histopathological features. Therapy is
      palliative rather than curative, and the prognosis is very poor.

PMID- 12239955
TI  - Mono-arthritis following intensified interferon beta therapy for chronic
      hepatitis C.
AB  - A 39-year-old man with chronic hepatitis C was administered interferon beta (3 MU
      twice a day) daily. Before interferon therapy, he did not have any symptoms and
      abnormal data related with autoimmune diseases. On the 16th day of interferon,
      mono-arthritis occurred at his right elbow. Anti-nuclear antigen or rheumatoid
      factor was still negative. Discontinuation of interferon for a week with non
      steroid anti-inflammatory drug relieved his symptom. Re-administration of
      interferon (6 MU once a day, three times a week) did not induce arthralgia any
      more. Administration of interferon beta twice a day may accelerate the cellular
      immunity twice. Careful observation should be taken even in the cases without pre
      existing autoimmune diseases.

PMID- 12239956
TI  - Graft survival following three occurrences of hepatic arterial thrombosis after
      living-related liver transplantation. A case report.
AB  - Hepatic arterial thrombosis is a major cause of morbidity and graft loss in
      patients undergoing liver transplantation. We report the case of a patient who
      underwent living-related liver transplantation and suffered three instances of
      early hepatic arterial thrombosis requiring revascularization in the first 8 days
      after grafting. The patient was discharged with good graft function. A 21-month
      old female with biliary atresia underwent living-related liver transplantation
      using her mother's extra-lateral segment. The donor middle hepatic artery was
      anastomosed end-to-end to the posterior branch of the donor's hepatic artery. The
      time of operation was 8 hr 36 min, and the blood loss was 193 mL. On
      postoperative day 5, the patient was returned to surgery to close a perforation
      in the transverse colon. At operation we found hepatic arterial thrombosis and
      performed a thrombectomy and redid the arterial anastomosis. Hepatic arterial
      thrombosis recurred during the operation, so we interposed the recipient's right
      radial artery between the graft artery and recipient posterior branch. On
      postoperative day 8, ultrasound showed a fluid collection in Winslow's pouch.
      After removing the fibrin clot, we discovered that hepatic arterial thrombosis
      had recurred in the interposed artery. We revascularized the graft using the
      right gastroepiploic artery. Arterial blood flow was restored, and graft function
      remained excellent.

PMID- 12239958
TI  - Hepatic angiosarcoma mimicking cavernous hemangioma on angiography.
AB  - A 60-year-old woman was admitted to our department for evaluation of a hepatic
      mass. The mass was diagnosed as a hemangioma of the liver by abdominal
      angiography because of typical cotton wool appearance and stretched arterial
      vessels and no peripheral staining. However, one month later, the mass was
      surgically removed because of extravasation. Histological findings of a specimen
      of the mass revealed that it entirely contained abundant necrotic tissue, and a
      small residual part after transcatheter arterial embolization was consistent with
      hemangioma. However, she complained of hemoptysis and thigh pain after several
      weeks. Computed tomography revealed multiple lung masses and a mass of right
      musculus gluteus medius. Reexamined histological findings of the liver tumor
      showed hemangiosarcoma. We should pay attention to the fact that it is sometimes
      difficult to differentiate cavernous hemangioma from angiosarcoma by angiography.

PMID- 12239957
TI  - A long-term survival case underwent repeated hepatic arterial infusion
      chemotherapy with portal branch ligation and wrapping of the liver using sheets
      for hepatocellular carcinoma.
AB  - Despite progress in therapeutic modalities for hepatocellular carcinoma,
      chemotherapy is the only remaining option for a considerable number of patients
      because of severe advanced disease and/or cirrhosis. Repeated hepatic arterial
      infusion chemotherapy with portal branch ligation and decollateralization using a
      silicone rubber sheet was performed for hepatocellular carcinoma. Tumor size and
      serum concentration of alpha-fetoprotein markedly decreased after hepatic
      arterial infusion chemotherapy. Although the patient had no recurrent tumor, he
      died of hepatorenal failure 7 years after treatment. Hepatic arterial infusion
      chemotherapy combined with portal branch occlusion and decollateralization is a
      new therapeutic method for unresectable hepatocellular carcinoma.

PMID- 12239959
TI  - Staging with helical computed tomography and laparoscopy in pancreatic head
      cancer.
AB  - BACKGROUND/AIMS: Helical computed tomography provides valuable information about
      extent of pancreatic cancer. However, it remains difficult to detect small
      distant metastases. Laparoscopic examination is becoming standard for cancer
      staging. METHODOLOGY: Between 1995 and 1999, 45 patients with radiologically
      resectable pancreatic head cancer were analyzed retrospectively to clarify the
      indications for and role of staging laparoscopy. Computed tomography was examined
      for tumor size and spread to portal or superior mesenteric veins (PV) and celiac
      or superior mesenteric arteries (A). RESULTS: There were 29 (64%) patients with
      resectable disease, 4 (9%) with localized unresectable, and 12 (27%) with
      metastatic (hepatic in 7 and peritoneal in 5). Patients with metastatic disease
      were more likely to present with abdominal pain, vomiting, and back pain than
      were patients with resectable disease (p < 0.05). The mean tumor size and
      involvement of PV or A were greater in metastatic patients than in resectable
      patients (p < 0.005 or p < 0.01). The survival rate for patients with metastatic
      disease was lower than that for patients with resectable disease (p < 0.0001).
      CONCLUSIONS: According to clinical features and computed tomography findings,
      laparoscopic exploration is recommended for cancer staging. Helical computed
      tomography and staging laparoscopy categorize patients into those with localized
      and those with metastatic disease which considerably correlated with survivals.

PMID- 12239960
TI  - Management of cystic neoplasms of the pancreas.
AB  - BACKGROUND/AIMS: Despite the growing interest in cystic neoplasms of the
      pancreas, their diagnosis, treatment and prognosis are still obscure and
      controversial. METHODOLOGY: We studied, from September 1989 to July 1999, 21
      patients (18 women) with an average age of 54.3 years who were submitted to
      surgical treatment for cystic neoplasms of the pancreas. Ultrasonography and
      computed tomography were performed in all patients. RESULTS: The treatment
      performed was surgical resection: cephalic gastroduodenopancreatectomy, 4
      patients; body and tail pancreatectomy, 11 patients; only tail pancreatectomy, 2
      patients; and two other patients were submitted to enucleation of one small
      lesion in the head of the pancreas. Internal drainage, through cystogastrostomy
      or cystojejunostomy, was performed in 3 cases. Site of tumor: body and tail
      region, 14 cases; head of the pancreas, 7 cases. Three patients had postoperative
      complications (respiratory tract infection, surgical wound infection, abdominal
      abscess). Three patients developed diabetes mellitus during the late
      postoperative period. One patient died 45 days after surgical procedure.
      CONCLUSIONS: Patients who present pancreatic cystic lesions should be submitted
      to surgery when local and medical conditions allow it and when intraoperative
      frozen biopsy excludes a pancreatic pseudocyst. If the nature of the lesion
      cannot be determined, it is better to err resecting a pseudocyst than by leaving
      or draining a cystic neoplasm, since these lesions are potentially curable.

PMID- 12239961
TI  - Does pancreaticosplenectomy contribute to better survival?
AB  - BACKGROUND/AIMS: This study was conducted to clarify the impact of
      pancreaticosplenectomy on the prognosis of patients with gastric carcinoma.
      METHODOLOGY: Two hundred and seventy-two patients who underwent total gastrectomy
      with distal pancreatectomy and splenectomy were retrospectively reviewed.
      RESULTS: Lymph node metastases at the splenic hilum (#10) and along the splenic
      artery (#11) occurred in 12.4% and 19.2% of cases, respectively. The 5-year
      survival rate of those without metastasis at #10 was 62.8%. Once nodal metastasis
      occurred, the prognosis became very poor; only 18.2% in those with a single
      positive node and 15.4% of those with two or more positive nodes at this location
      survived 5 years. Similar trends in survival were observed with respect to nodes
      at #11. When stratified by nodal status as currently determined by microscopic
      examination, pancreaticosplenectomy saved 4.5% of patients with positive nodes,
      but was insufficient in 17.3% of cases and was not necessary in the 78.2% of
      cases who were node negative at these locations. CONCLUSIONS: The data indicate
      that pancreaticosplenectomy can save some patients with positive nodes in these
      regions; however, the small survival benefit does not provide a basis for the
      general application of this highly morbid procedure. To further evaluate these
      results in a randomized study, selection of a subset of patients who are likely
      to have metastasis is the key.

PMID- 12239962
TI  - Intraductal papillary and mucinous tumor of the pancreas: a case report of
      successful surgical treatment with decompression.
AB  - Intraductal papillary mucinous tumor of the pancreas is commonly regarded as
      histopathologically low-grade malignancy. As yet, no fixed strategy of treatment
      for the advanced aged patient with intraductal papillary mucinous tumor exists.
      An 80-year-old woman was admitted to our hospital in July 1996 because of back
      pain due to pancreatitis. Examinations showed a widely opened orifice of the
      ampulla of Vater, the mural nodule in the cystic lesion of the pancreas uncus,
      and a mucinous plug in the diffusely dilated main pancreatic duct, so the patient
      was diagnosed as having intraductal papillary mucinous tumor in the pancratic
      head. However, in view of the patient's advanced age and the fact that
      intraductal papillary mucinous tumor is commonly regarded as a slow growing and
      histopathologically low-grade malignancy, we refrained from radical operation and
      selected the best supportive care. Four years subsequent to this, her symptoms
      became uncontrollable and she returned to our hospital. In consideration of her
      age, side-to-side pancreaticojejunostomy as minimally invasive surgery was
      employed. The postoperative course was uneventful. The symptoms, biochemical
      profiles and images improved and she was discharged from the hospital 28 days
      after the operation. No event has been observed in the patient for one year after
      operation. Surgical decompression is considered to be effective minimally
      invasive surgery for intraductal papillary mucinous tumor.

PMID- 12239963
TI  - Long-term hematological and biochemical effects of partial splenic embolization
      in hepatic cirrhosis.
AB  - BACKGROUND/AIMS: Partial splenic embolization was developed as a non-surgical
      treatment for hypersplenism, but recently splenic embolization has been reported
      to improve the hepatic function. We undertook long-term evaluation of partial
      splenic embolization in patients with hepatic cirrhosis in comparison with
      patients not undergoing embolization. METHODOLOGY: We performed embolization in
      26 patients with cirrhosis. The controls consisted of 26 with cirrhosis patients
      who were not undergone embolization. RESULTS: Red blood cell counts of embolized
      patients had increased significantly at 6 months after the procedure, remaining
      increased for up to 7.5 years. Platelet counts increased maximally by 2 weeks
      after embolization, followed by a gradual decrease. Nonetheless, platelets
      remained significantly more numerous than before embolization for up to 8 years.
      Neither aspartate aminotransferase nor alanine aminotransferase activities in
      serum changed significantly during follow-up. Choline esterase activity increased
      significantly by 6 months after embolization and remained increased for more than
      7 years. Serum albumin concentration increased significantly, beginning at 6
      months after embolization; this increase was maintained for 6 years. Survival did
      not differ between embolized and non-embolized groups. CONCLUSIONS: Partial
      splenic embolization is a beneficial non-surgical treatment that enhances hepatic
      protein synthetic capacity as well as alleviating hypersplenism in patients with
      cirrhosis.

PMID- 12239964
TI  - Solitary lymph node metastasis of gastric cancer as a basis for sentinel lymph
      node biopsy.
AB  - BACKGROUND/AIMS: In order to examine the biology of sentinel lymph node of
      stomach cancer, we investigated solitary lymph node metastases that were
      hypothesized to represent sentinel lymph node. METHODOLOGY: In the 4,620 primary
      gastric cancers between 1964 and 1997, 1271 cases with a localized tumor were
      selected and the localization of the solitary metastases in relation to the
      primary tumors were studied. RESULTS: Of the 130 tumors with a single basin
      metastasis, only 71% of the tumors in the upper third, 75% of the middle and 80%
      of the lower involved the node basins in the close vicinity. In the anterior wall
      and the greater curvature the rates of adjacent metastasis were more than 90%,
      while in the posterior wall and the lesser curvature they were 76% and 43%,
      respectively. Metastases of the remaining cases were found at more distant
      basins. CONCLUSIONS: In stomach cancer sensitivity of sentinel lymph node biopsy
      would be very low by the exploration of the adjacent basin especially for the
      lesions in the lesser curvature and posterior wall.

PMID- 12239965
TI  - Tumor angiogenesis increases with nuclear p53 accumulation in gastric carcinoma.
AB  - BACKGROUND/AIMS: Tumor angiogenesis is associated with disease stage in gastric
      carcinoma. The tumor suppressor p53 was recently reported to regulate
      angiogenesis. We investigated the relationship between nuclear p53 accumulation
      and tumor vascularity in gastric carcinoma. METHODOLOGY: Patients with gastric
      carcinoma undergoing surgery were randomly enrolled. Nuclear p53 expression
      assessed by immunohistochemistry on tumor sections was categorized as higher and
      lower groups. Tumor vascularity was assessed by counting microvessel density on
      anti-CD34 stained sections. Tumor vascularity between different p53 expressions
      was compared based on the different clinicopathologic characteristics. RESULTS:
      Twenty-three patients had gastric carcinoma with higher nuclear p53 expression
      and 42 with lower nuclear p53 expression. Vascularity in higher p53 group (54.3
      +/- 35.3) was significantly higher than that in lower p53 group (32.1 +/- 29.9)
      (p = 0.009). Further analysis showed that higher nuclear p53 immunoreactivity was
      associated with significantly higher vascularity in the advanced gastric
      carcinoma group (p = 0.023), the intestinal type group (p = 0.003), the non
      cardiac group (p = 0.019), and the H. pylori-negative group (p = 0.014).
      CONCLUSIONS: The present study demonstrated that nuclear p53 protein expression
      positively associates vascularity in gastric carcinoma although their
      relationship varies in the different clinicopathologic subsets.

PMID- 12239966
TI  - The effect of stress on gastric emptying rate measured with a radionuclide
      tracer.
AB  - BACKGROUND/AIMS: Stress can delay gastric emptying rate. This phenomenon has not
      yet been investigated with a physiological solid test meal or a regional
      analysis. METHODOLOGY: We investigated the gastric emptying rate in beagle dogs
      using a radio-labeled solid test meal and a gamma camera. The transport to an
      unknown environment served as a stress stimulus. This offers the advantage to
      mimic fairly well the clinical situation just before a diagnostic or therapeutic
      procedure. Control values were obtained after the third investigation, in which
      all dogs were accustomed to the environment. RESULTS: Regional analysis of the
      emptying curves from the whole gastric region revealed that the length of the lag
      phase increased with stress, but the post-initial emptying rate remained
      unchanged. Emptying of the fundus changed hardly, but the antropyloral motor
      activity decreased during stress. CONCLUSIONS: Gastric emptying rate is impeded
      during stress. It is necessary to limit the unnatural stress-stimuli, in order to
      mimic the clinical situation. Measurement techniques that influence directly
      gastric emptying or act as a stress-stimulus by themselves are undesirable. A
      radionuclide solid test meal is preferable and a regional analysis reveals the
      impairment of the antral motility as the mechanism of the delay of gastric
      emptying.

PMID- 12239967
TI  - Jejunal interposition helps prevent reflux gastritis.
AB  - BACKGROUND/AIMS: Jejunal interposition after distal gastrectomy is reported to
      prevent both duodenogastric reflux and rapid gastric emptying. However, comparing
      primary reconstruction with this procedure and Billroth-I in terms of clinical
      evaluation by the same surgeon is rare. In this study, the benefit of this
      procedure was retrospectively evaluated as compared to the Billroth-I method.
      METHODOLOGY: Of 30 patients with early gastric cancer located at the middle third
      of the stomach, 15 underwent distal gastrectomy with jejunal interposition and
      the other 15 underwent Billroth-I gastrectomy by the same surgeon. Isoperistaltic
      jejunal interposition measuring 10-12 cm was used. All the anastomoses without
      jejunojejunostomy were performed using auto-suture staplers. Assessment of
      postoperative symptoms and functions was performed one year after surgery.
      RESULTS: The mean operation time was significantly longer after jejunal
      interposition (p < 0.01). No serious complications occurred in either group, and
      the hospital stay after operation was also similar. There were no significant
      differences in terms of postoperative symptoms, food intake, and recovery of body
      weight. The incidence of bile regurgitation and reflux gastritis was very low or
      zero in the jejunal interposition group, which indicated differences (p < 0.05, p
      < 0.01, respectively). Reflux esophagitis was not found in jejunal interposition,
      but two patients after Billroth I showed grade B esophagitis. As regards gastric
      emptying, the retention capacity was very poor and there was no significant
      difference between the two groups. CONCLUSIONS: Jejunal interposition after
      distal gastrectomy was superior to the Billroth-I procedure in terms of reflux
      gastritis prevention. However, dumping syndrome and rapid gastric emptying were
      not prevented.

PMID- 12239968
TI  - Lymph node metastasis in early gastric cancer: a clinicopathological analysis.
AB  - BACKGROUND/AIMS: Endoscopic mucosal resection and laparoscopic wedge resection
      have become more common in the treatment of early gastric cancer. However, lymph
      node metastasis is a major poor prognostic factor influencing tumor recurrence
      and survival. To predict the risk of lymph node metastasis in early gastric
      cancer, the authors conducted a study to investigate the clinicopathologic
      characteristics of early gastric cancer with lymph node metastasis. METHODOLOGY:
      From 1982 to 1998, 181 patients of early gastric cancer underwent primary surgery
      and were included in the study. Patient data was postoperatively reviewed
      regarding age, gender, tumor size, depth of invasion, histologic differentiation,
      macroscopic classification and anatomic level of lymph node metastasis. The chi 2
      test or Student's t test was used for statistical analysis. Logistic regression
      analysis was used to evaluate the independent risk factors for lymph node
      metastasis. RESULTS: Lymph node metastasis was observed in 19 cases (11%). Early
      gastric cancer with size larger than 4 cm (P < 0.05), with submucosal invasion (P
      < 0.01), and with poor differentiation (P < 0.05) was associated with higher risk
      of lymph node metastasis. The macroscopic classification had no predictive value.
      Multivariate analysis showed that submucosal invasion correlated best with lymph
      node spread (OR 10.25, 95% CI: 2.10-49.96), followed by tumor size larger than 4
      cm (OR 4.99, 95% CI: 1.46-17.05), and poorly differentiated histological subtype
      (OR 3.31, 95% CI: 1.16-9.45). CONCLUSIONS: Poor differentiation, submucosal
      invasion and large tumor size were independent risk factors for lymph node
      metastasis in early gastric cancer. Macroscopic classification was not correlated
      with lymph node metastasis.

PMID- 12239969
TI  - Billroth I versus Billroth II versus Roux-en-Y after subtotal gastrectomy.
      Prospective [correction of prespective] randomized study.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate functional results after
      Billroth I, Billroth II and Roux-en-Y reconstruction in subtotal gastrectomy.
      METHODOLOGY: Forty-five patients were randomized between 1990 and 1995 and
      stratified in 3 different groups: 15 BI, 15 BII and 15 Roux. They were
      investigated by esophagogastroduodenoscopy with multiple biopsies and upper
      gastrointestinal scintiscanning, to evaluate gastroesophageal reflux and dynamics
      of gastric emptying. They also answered a questionnaire: Gastrointestinal Quality
      of Life. Index. RESULTS: A reflux esophagitis was found in 5 BI, in 7 BII and in
      2 Roux (p < 0.001). No gastric lesions were found in 6 BI, in 5 BII and in 12
      Roux, (BI vs. Y, p < 0.05; BII vs. Y, p < 0.001). Chronic superficial gastritis
      was present in 9 BI, in 4 BII and in 3 Roux (BI vs. Y, p < 0.05). Dynamic
      scintiscan demonstrated the presence of gastroesophageal reflux in 5 BI and
      gastric emptying was fast (37' < T 1/2 < 86'), but incomplete (60' residual
      activity: 49-62%). Gastroesophageal reflux was evident in 7 BII with slow (28' <
      T 1/2 < 143') and incomplete (60' residual activity: 48-72%) gastric emptying.
      Gastroesophageal reflux was detected in 2 Roux and radioactive bolus progression
      in the Roux limb was fast (24' < T 1/2 < 53') and complete (60' residual
      activity: 42-52%) (BI vs. Y; BII vs. Y, p < 0.001). There was no statistical
      significance between Gastrointestinal Quality of Life Index score in the 3
      groups. CONCLUSIONS: The Authors affirm that Roux-en-Y is the technique of choice
      in subtotal gastrectomy, if compared with BI and BII.

PMID- 12239970
TI  - Association of polymorphisms of interleukin-1 beta gene and Helicobacter pylori
      infection with the risk of gastric ulcer.
AB  - BACKGROUND/AIMS: Interleukin-1 beta (IL-1 beta) plays an important role in
      gastric inflammation and physiology. Functional polymorphisms of IL-1 beta gene
      have been related to different risks of gastric cancer and duodenal ulcer but
      their role in gastric ulcer remains unknown. In this study, we investigate a
      plausible association between gastric ulcer and the polymorphisms in the IL-1
      beta and IL-1 receptor antagonist (IL-1RN) genes. The relationships among the
      cytokine genotyping, other environmental risks such as Helicobacter pylori
      infection and smoking, and clinical characteristics of gastric ulcer were also
      determined. METHODOLOGY: Peripheral blood DNAs from 120 unrelated Taiwan Chinese
      patients with gastric ulcer and 238 ethnically matched healthy controls were
      genotyped for the promoter (position -31 and -511) and Taq I polymorphism
      (position +3954) in the IL-1 beta gene and the variable number of tandem repeats
      polymorphisms in intron 2 of the IL-1RN gene. The status of Helicobacter pylori
      infection was determined by serology. RESULTS: The seropositive rate of
      Helicobacter pylori (95/120 vs. 134/238, OR: 2.95, 95%CI 1.77-4.91), habitual
      smoking (67/120 vs. 82/238, OR: 2.40, 95%CI 1.54-3.77) and blood group O (63/120
      vs. 98/238, OR: 1.55, 95%CI 1.0-2.41) were significantly higher in patients with
      gastric ulcer than controls. The distributions of allele frequencies of IL-1 beta
      (-31 C/T or -511 C/T or +3954) and IL-1RN were similar between patients with
      gastric ulcer and controls. No significant differences were observed, including
      those analyzed after stratification of the infected population and by the ulcer
      subgroup. CONCLUSIONS: Our data suggested that Helicobacter pylori infection,
      cigarette smoking, and blood group O are risk factors of gastric ulcer and IL-1
      beta or IL-1RN polymorphisms do not influence susceptibility to gastric ulcer in
      a Taiwanese population.

PMID- 12239972
TI  - Commentary: rural health can help lead the way.

PMID- 12239971
TI  - Indications for pylorus-preserving gastrectomy for gastric cancer based on lymph
      node metastasis.
AB  - BACKGROUND/AIMS: It is necessary to study the relation between lymph node
      metastasis in the suprapyloric or lesser curvature regions and clinicopathologic
      findings in order to determine the indications for pylorus-preserving
      gastrectomy. METHODOLOGY: We reviewed all pertinent data from the cases of 109
      patients with gastric cancer located mainly in the middle third of the stomach
      focusing particularly on status of lymph node metastasis and clinicopathologic
      findings. All patients had been treated by conventional gastrectomy with regional
      lymph node dissection (D2 or D3). RESULTS: Lymph node metastases were found in
      the lesser curvature or suprapyloric regions in 18 patients. Primary tumors were
      located in the lesser curvature side in 15 of these 18 patients and in the
      greater curvature side in only 3. Primary tumors in the greater curvature side
      with involvement in the lesser curvature or suprapyloric lymph nodes were greater
      than 4.0 cm in diameter, whereas primary tumors in the lesser curvature side with
      such metastasis were greater than 1.3 cm. CONCLUSIONS: Indications for pylorus
      preserving gastrectomy with preserving of the pyloric branch of the vagal nerve
      perhaps can be expanded to middle stomach cancer located in the greater curvature
      side that is less than 4.0 cm in diameter.

PMID- 12239973
TI  - Antibiotic resistance: unnatural selection in the office and on the farm.

PMID- 12239974
TI  - Protecting children from agricultural injuries.

PMID- 12239975
TI  - Addressing rural health from a public health perspective.

PMID- 12239976
TI  - Pesticide exposure, host susceptibility factors and risk of Parkinson's disease:
      an introduction to a work in progress.

PMID- 12239977
TI  - Recruiting physicians to rural areas. What is the prescription for success?

PMID- 12239978
TI  - One successful approach.

PMID- 12239979
TI  - A smoking cessation clinic with a 57% success rate: what makes it work?
AB  - OBJECTIVE: To describe an outpatient smoking cessation clinic, and what predicts
      participant success. METHODS: In 1999, a 12-week smoking cessation clinic was
      begun. In 2000, the duration was expanded to include an additional 12 weeks of
      relapse prevention. Participants completed surveys at the beginning and end of
      their clinic. All participants, even those who dropped out, were surveyed to
      determine current status. If they were not reached, they were assumed to be
      smoking. RESULTS: Eleven clinics have been completed thus far, with 117 people
      enrolling. Of all participants, 57% were not smoking at their last contact
      (average length of follow-up was 14 months). Age, baseline smoking rate, and
      presence of a non-smoking support person were the best predictors of abstinence.
      CONCLUSIONS: A 57% abstinence rate was achieved in this outpatient clinic,
      serving a mix of rural and non-rural patients.

PMID- 12239980
TI  - Colorectal cancer screening: physician attitudes and practices.
AB  - PURPOSE: The American Cancer Society (ACS) set a nationwide goal to increase to
      75% by 2015 the proportion of people aged 50 and older who have colorectal cancer
      (CRC) screening consistent with ACS guidelines. Little is known about current
      physician screening practices and attitudes. The purpose of this study was to
      document current physician attitudes and practices regarding CRC screening, and
      to formulate appropriate interventions to meet the ACS screening goal. METHODS:
      Questionnaires were sent to a random sample of 600 primary care physicians in
      Wisconsin. The survey measured 1) screening preferences; 2) estimates of patients
      screened by each method; 3) agreement to statements regarding screening
      guidelines and practices, patient compliance, effectiveness in reducing
      mortality, factors regarding colonoscopy as a screening tool; 4) use of reminder
      systems; 5) demographics. RESULTS: Physicians prefer combining fecal occult blood
      testing (FOBT) with flexible sigmoidoscopy for CRC screening, while they believe
      patients prefer FOBT alone. Only 1.5% view colonoscopy as their preferred method
      of screening. There is discrepancy between physicians' beliefs that patients
      should be screened and estimated numbers they screen. Only 38.2% of respondents
      would screen a moderate-risk patient at the ACS recommended age. Physicians
      perceive screening compliance to be low. Cost, availability, risks, and lack of
      proof of effectiveness influence physician decisions. Fewer than half have any
      reminder system for CRC screening. CONCLUSIONS: CRC screening rates are currently
      lower than the 2015 ACS goal. Influential factors include physician attitudes and
      beliefs about effectiveness, familiarity with guidelines, perception of patient
      preferences and compliance, and lack of adequate reminder systems. Targeting
      interventions to these factors may increase the rate of CRC screening. Despite
      increased consensus from professional societies on colonoscopy as the best choice
      for screening, few primary care physicians would choose this option.

PMID- 12239981
TI  - Polypoid angiomyofibroblastoma: a case report and review of the literature.
AB  - A case of a polypoid angiomyofibroblastoma of the distal anterior vaginal vault
      in a 56-year-old woman is presented. Clinical, histological, and
      immunohistochemical features of this entity are discussed, along with the
      differential diagnosis and a review of the literature.

PMID- 12239982
TI  - Atypical presentation of subarachnoid hemorrhage: case report and review of the
      literature.
AB  - Subarachnoid hemorrhage is a threatening condition often associated with
      significant morbidity and mortality. The risk of rebleeding and ischemic
      complications can be markedly reduced when the prompt diagnosis of cerebral
      aneurysmal rupture is made. The sudden onset of severe headache with or without
      neurologic deficit raises the clinical suspicion, however atypical symptoms exist
      making the diagnosis difficult. A 49-year-old male with a 3-day history of neck
      discomfort, without headache, was admitted following a generalized seizure. A
      serum sodium of 115 mEq/L was noted. A computed tomographic scan of the brain
      revealed a subarachnoid hemorrhage. Two intracranial cerebral aneurysms were
      identified by cerebral angiography and subsequently treated. The diagnosis and
      treatment of subarachnoid hemorrhage is reviewed.

PMID- 12239983
TI  - Changes ahead for Medicare appeals process.

PMID- 12239984
TI  - Clinical flow cytometry: milestones along the pathway of progress.

PMID- 12239985
TI  - Rolf Classon, president of Bayer Diagnostics, shares his views. Interview by C.
      Anne Pontius.

PMID- 12239986
TI  - Who should supervise children in a patient waiting area?

PMID- 12239988
TI  - Catalytic reactions in ionic liquids.
AB  - The chemical industry is under considerable pressure to replace many of the
      volatile organic compounds (VOCs) that are currently used as solvents in organic
      synthesis. The toxic and/or hazardous properties of many solvents, notably
      chlorinated hydrocarbons, combined with serious environmental issues, such as
      atmospheric emissions and contamination of aqueous effluents is making their use
      prohibitive. This is an important driving force in the quest for novel reaction
      media. Curzons and coworkers, for example, recently noted that rigorous
      management of solvent use is likely to result in the greatest improvement towards
      greener processes for the manufacture of pharmaceutical intermediates. The
      current emphasis on novel reaction media is also motivated by the need for
      efficient methods for recycling homogeneous catalysts. The key to waste
      minimisation in chemicals manufacture is the widespread substitution of classical
      'stoichiometric' syntheses by atom efficient, catalytic alternatives. In the
      context of homogeneous catalysis, efficient recycling of the catalyst is a
      conditio sine qua non for economically and environmentally attractive processes.
      Motivated by one or both of the above issues much attention has been devoted to
      homogeneous catalysis in aqueous biphasic and fluorous biphasic systems as well
      as in supercritical carbon dioxide. Similarly, the use of ionic liquids as novel
      reaction media may offer a convenient solution to both the solvent emission and
      the catalyst recycling problem.

PMID- 12239987
TI  - Working short again? Absenteeism exacts toll from patient care, employee morale.

PMID- 12239989
TI  - A surprisingly mild and versatile method for palladium-catalyzed Suzuki cross
      couplings of aryl chlorides in the presence of a triarylphosphine.
AB  - In the presence of new air-stable triarylphosphine 2, palladium-catalyzed Suzuki
      reactions of a wide array of aryl chlorides can be accomplished in uniformly good
      yield, including couplings of very sterically demanding and electronically
      deactivated substrates; activated aryl chlorides can be coupled at room
      temperature. In terms of scope and mildness, Pd-2 compares well with other
      catalyst systems that have been described for Suzuki reactions of aryl chlorides,
      thereby establishing that triarylphosphines should be regarded as fertile ground
      for future ligand-design efforts for palladium-catalyzed couplings of aryl
      chlorides.

PMID- 12239990
TI  - Linear dichroism for the detection of single base pair mutations.
AB  - Flow linear dichroism is shown to be able to detect single base mismatches in a
      polymerase chain reaction (PCR) amplimers from exon 10 of the human beta
      glucocerebrosidase gene (associated with Gaucher disease) over a kilobase long
      with no post PCR manipulation.

PMID- 12239991
TI  - Visible light-induced photoepoxidation of propene by molecular oxygen over
      chromia-silica catalysts.
AB  - Highly dispersed chromate species on silica catalyse the selective epoxidation of
      propene to propene oxide (PO) by molecular oxygen under visible light irradiation
      with the same quantum yield as that under UV light irradiation.

PMID- 12239992
TI  - Reactivity in polynuclear transition metal chemistry as a means to obtain high
      spin molecules: substitution of mu 4-OH- by eta 1,mu 4-N3- increases nine times
      the ground-state S value of a nonanuclear nickel(II) cage.
AB  - The reaction of di-2-pyridyl ketone, (2-py)2CO, with Ni(O2CMe)(2).4H2O yields the
      cage [Ni9(OH)2(O2CMe)8((2-py)2CO2)4], which reacts further with N3- ions to give
      the structurally similar cluster [Ni9(N3)2(O2CMe)8((2-py)2CO2)4] containing
      extremely rare eta 1,mu 4-N3- groups; magnetic studies reveal that the spin
      ground state of the latter is nine times the ground state of the former.

PMID- 12239993
TI  - Stoichiometric water splitting into H2 and O2 using a mixture of two different
      photocatalysts and an IO3-/I- shuttle redox mediator under visible light
      irradiation.
AB  - The stoichiometric splitting of water into H2 and O2 (H2/O2 = 2) under visible
      light irradiation (lambda > 420 nm) took place for the first time using a mixture
      of Pt-WO3 and Pt-SrTiO3 (Cr-Ta-doped) photocatalysts and an IO3-/I- shuttle redox
      mediator.

PMID- 12239994
TI  - A low cost route to hexagonal mesostructured carbon molecular sieves.
AB  - A mesoporous carbon molecular sieve with a hexagonal framework structure (denoted
      C-MSU-H) has been prepared using a MSU-H silica template that can be assembled
      from a low cost soluble silicate precursor at near-neutral pH conditions.

PMID- 12239995
TI  - Tuning the recovery of an Rh-containing catalyst with silica-based (poly) amine
      ion exchangers.
AB  - Highly efficient Rh-recovery from different adsorption media has been effected
      with silica-based (chelating) ion exchangers containing (poly) amine
      functionalities; recoveries have been found to correlate well with the stability
      of the metal-to-ligand complexes.

PMID- 12239996
TI  - Silicon-29 diffusion-ordered NMR spectroscopy (DOSY) as a tool for studying
      aqueous silicates.
AB  - The first use of silicon-29 diffusion-ordered NMR spectroscopy (DOSY) is
      reported, in a study of the speciation of aqueous silicates.

PMID- 12239997
TI  - Reversible encapsulation of multiple, neutral guests in hexameric resorcinarene
      hosts.
AB  - A variety of aromatic guest molecules are co-encapsulated with Bu4SbBr in an
      assembly of six resorcinarene subunits.

PMID- 12239998
TI  - New fluorocarbon iodides.
AB  - A general, efficient approach for the synthesis of fluorocarbon iodides and di
      iodides bearing hydrocarbon groups is described and the synthetic utility of
      these new systems is demonstrated in reactions with thiols.

PMID- 12239999
TI  - Synthesis of a highly thermally stable octupolar polyimide for nonlinear optics.
AB  - A new polyimide with covalently incorporated 4,4'-bis-(dialkylaminostyryl)-2,2'
      bipyridine chromophores is described which allows the synthesis of the
      corresponding NLO octupolar metallo-polymer.

PMID- 12240000
TI  - Ferrocene-modified bis(spiropyridopyran)s as synthetic signaling receptors for
      guanine-guanine dinucleoside derivatives.
AB  - A ferrocene-linked bis(spiropyridopyran) was designed and synthesized, that
      recognized guanine-guanine dinucleoside derivatives via complementary hydrogen
      bonds in CH2Cl2, resulting in the isomerization of the colorless spiropyridopyran
      as self-indicating receptors.

PMID- 12240001
TI  - More than just a catalyst: a novel role for benzylamine in the sol-gel
      transcription of organogels.
AB  - Gelator-catalyst interactions allow the transcription of the organogel structure
      of methyl-4,6-O-(p-nitrobenzylidene)-alpha-D-glucopyranoside (1) into its silica
      analogue, even in the absence of positive charges or H-bonding sites on the
      gelator molecule which, until now, were considered indispensable.

PMID- 12240002
TI  - A cascade of reactions involving anchimeric assistance leads to a highly
      'crowded' hexa(alkylcarboxy)benzene.
AB  - The substitution of hexabromomethylbenzene with 1-adamantyl carboxylate
      quantitatively leads to the corresponding hexacyl derivative via anchimeric
      assistance by the alkylcarboxy substituents.

PMID- 12240003
TI  - A new one-pot three-component condensation reaction for the synthesis of 5-deaza
      5,8-dihydropterins.
AB  - The one-pot cyclocondensation of 2,6-diaminopyrimidin-4-one, an aromatic or
      aliphatic aldehyde and a beta-ketoester in acetic acid, or dimethyl sulfoxide in
      the presence of zinc(II) bromide, under thermal conditions provided
      dihydropyrido[2,3-d]pyrimidin-4(3H)-ones in good yield and with total
      regiocontrol.

PMID- 12240004
TI  - Catalytic asymmetric synthesis of cyclopentenones from propargyl malonates and
      allylic acetate by successive action of homogeneous palladium(II) and cobalt on
      charcoal catalysts in a one-pot reaction.
AB  - The tandem action of a homogeneous chiral Pd(II) catalyst and a heterogeneous
      Co/C catalyst leads to a two-step one-pot highly enantioselective Pauson-Khand
      type reaction.

PMID- 12240005
TI  - Multilayer structure of an unsymmetrical monolayer lipid membrane with a 'head-to
      tail' interface.
AB  - A synthetic unsymmetrical 1-galactosamide bolaamphiphile self-assembles in
      methanol to form a multilayer structure comprising unsymmetrical monolayer lipid
      membranes linked via a sugar-carboxylic acid H-bonding interface.

PMID- 12240007
TI  - A novel way to prepare ultra-thin polymer films through surface radical chain
      transfer reaction.
AB  - Radical chain transfer to bonded thiol groups and surface re-initiated
      polymerization resulted in ultra-thin polymer films.

PMID- 12240006
TI  - Uniform thin films of poly-3,4-ethylenedioxythiophene (PEDOT) prepared by in-situ
      deposition.
AB  - In-situ deposited thin films of the conducting polymer poly-3,4
      ethylenedioxythiophene (PEDOT) have been prepared on hydrophilic and hydrophobic
      substrates and characterized by UV-Vis spectroscopy, atomic force microscopy and
      resistivity measurements.

PMID- 12240008
TI  - Dissociative cycloelimination, a new selenium based pericyclic reaction.
AB  - The stereospecific oxidation of hydrazine into cis-diimide and the catalytic
      disproportionation of hydrogen peroxide effected by selenoxides are suggested to
      involve a dissociative cycloelimination from an intermediary selenurane.

PMID- 12240009
TI  - Regiocontrolled deprotonative-zincation of bromopyridines using aminozincates.
AB  - Regiochemistry in the deprotonation of bromopyridines was found to be greatly
      influenced by the choice of metal amide base, and DA-zincate and TMP-zincate
      turned out to be excellent complementary practical agents for regioselective
      metalation of bromopyridines.

PMID- 12240010
TI  - Ion-carrier controlled precipitation of calcium phosphate in giant ABA triblock
      copolymer vesicles.
AB  - An ionophore assisted metal-ion transport across block copolymer membranes has
      been used to control the local Ca2+ concentration during precipitation of calcium
      phosphate in giant block copolymer vesicles.

PMID- 12240011
TI  - Decreased methane formation from the hydrogenation of carbon monoxide using
      zeolite/cobalt-manganese oxide composite catalysts.
AB  - A composite catalyst comprising a physical mixture of a zeolite and a
      cobalt/manganese oxide Fischer-Tropsch catalyst decreases the formation of
      methane in the hydrogenation of carbon monoxide without significantly affecting
      conversion.

PMID- 12240012
TI  - Synthesis of cyclopentadienones catalyzed by methylidynetricobalt nonacarbonyl.
AB  - Easily prepared and air-stable methylidynetricobalt nonacarbonyl could be used as
      a catalyst for the intramolecular [2 + 2 + 1]-cocyclization of diynes and carbon
      monoxide producing cyclopentadienones.

PMID- 12240013
TI  - EPR and NMR spectroscopic studies of [MoL2(MeC identical to CMe)Cp]z (L = P-donor
      ligand, z = 0 and 1): fluxionality in a metal-alkyne redox pair.
AB  - Variable temperature NMR and EPR spectroscopic studies provide rates and
      activation parameters for alkyne rotation and oscillation, respectively, in the
      fluxional redox pair [Mo(P(OMe)3)2(MeC identical to CMe)Cp][BF4] (diamagnetic)
      and [Mo(P(OMe)3)2(MeC identical to CMe)Cp] (paramagnetic).

PMID- 12240014
TI  - Epoxidation of allylic alcohols in aqueous solutions of non surfactant
      amphiphilic sugars.
AB  - A variety of cyclic and acyclic allylic alcohols undergo efficient chemo-, regio-
      and/or stereoselective epoxidations in neutral aqueous solutions of amphiphilic
      carbohydrates (sucrose, L-arabinose, methyl or ethyl beta-D-fructopyranoside) by
      using dilute hydrogen peroxide in the presence of molybdic or tungstic salts.

PMID- 12240015
TI  - Exploiting modularity in template-controlled synthesis: a new linear template to
      direct reactivity within discrete hydrogen-bonded molecular assemblies in the
      solid state.
AB  - Co-crystallization of 1,8-naphthalenedicarboxylic acid (1,8-nap) with trans-1,2
      bis(n-pyridyl)ethylene (n,n'-bpe) (n = 2 or 4) yields a discrete four-component
      molecular assembly, 2(n,n'-bpe).2(1,8-nap) 1, that is held together by four O
      H...N hydrogen bonds where the dicarboxylic acid, serving as a linear template,
      directs alignment of olefins in the solid state for [2 + 2] photoreaction.

PMID- 12240016
TI  - Synthesis and DNA-binding properties of dinuclear platinum(II)-amine complexes of
      1,7-dicarba-closo-dodecaborane(12).
AB  - The first examples of platinum(II)-amine complexes containing a dicarba-closo
      dodecaborane(12) (carborane) moiety are described; preliminary in vitro DNA
      binding experiments indicate that the complexes are capable of targetting plasmid
      DNA.

PMID- 12240017
TI  - How van der Waals bonds orient molecules in zeolites.
AB  - We show that weak bonds are responsible for the way a molecule is held in a
      zeolite, and for its reactivity.

PMID- 12240018
TI  - Silver(I) carboxylates: versatile inorganic analogs of carboxylic acids for
      supramolecular network formation.
AB  - Dimeric motifs formed by silver(I) carboxylates, illustrated here by the unit
      Ag2(CF3CO2)2, resemble the well known dimerization of carboxylic acids, i.e.
      'H2(RCO2)2', but exhibit greater flexibility, while permitting further
      elaboration into neutral coordination networks through linkage of the silver
      centres via ditopic ligands.

PMID- 12240019
TI  - Synthesis of p-benzylcalix[4]arene and its sulfonated water soluble derivative.
AB  - p-Benzylcalix[4]arene is formed in good yield by a direct "one pot" reaction
      involving p-benzylphenol and formaldehyde, selectively converted to the
      corresponding chlorosulfonyl and sulfonate analogues.

PMID- 12240020
TI  - An extended chain structure formed by covalently linking polyoxovanadate cages
      with tetrahedral six rings.
AB  - The compound Cs10.5[(V16O40)(Si4.5V1.5O10)].3.5H2O is the first example of an
      extended structure in which a polyoxometallate anion is linked by an extended
      tetrahedral unit.

PMID- 12240021
TI  - Protein-calixarene interactions: complexation of Bovine Serum Albumin by
      sulfonatocalix[n]arenes.
AB  - The complexation of Bovine Serum Albumin with sulfonatocalix[n]arenes has been
      demonstrated by means of electrospray mass spectrometry, dynamic light scattering
      and atomic force microscopy; with sulfonatocalix[4]arene one strong and two
      weaker binding sites are detected; the effects on the structure of thin films
      formed by surface deposition of BSA show that the sulfonatocalix[n]arenes act to
      reticulate the films and produce essentially planar systems.

PMID- 12240022
TI  - Formation of a novel porphyrin-gold nanoparticle network film induced by IR light
      irradiation.
AB  - IR light irradiation of a mixed toluene solution of ammonium salt-stabilized gold
      nanoparticles with 3.8 +/- 0.8 nm core diameter and a porphyrin thioacetate
      derivative affords a thin photoactive film of the cluster-porphyrin network.

PMID- 12240023
TI  - Si-BEZA--catalytic pyridinium triflate: a mild and powerful agent for the
      silylation of alcohols.
AB  - A highly efficient method of silylation using a novel agent, Si-BEZA
      (silylbenzamide), together with a pyridinium triflate catalyst was developed,
      wherein a variety of silyl groups can be introduced into sterically crowded
      alcohols under mild conditions.

PMID- 12240024
TI  - The first example of a diazaarsolyl anion: structure and coordination
      polymerisation of the aromatic metallacycle benzo[1,3,2]diazaarsolyl
      lithium.2THF.
AB  - The first example of an aromatic diazaarsolyl anion 1 has been synthesised and
      structurally characterised; the X-ray crystal structure of 1 exhibits planar
      metallacyclic fragments which link together to generate a coordination polymer
      via bridging lithium cations.

PMID- 12240025
TI  - Bis[hydrotris(pyrazol-1-yl)borato]titanium(II): a stable Tp2M complex of singular
      reactivity.
AB  - Tp2Ti [Tp = hydrotris(pyrazol-1-yl)borate] is a stable hard donor complex of
      divalent titanium that shows controlled reaction chemistry with simple chalcogen
      oxidants.

PMID- 12240026
TI  - Hydrophobic ionic liquids incorporating N-alkylisoquinolinium cations and their
      utilization in liquid-liquid separations.
AB  - The first examples of Room Temperature Ionic Liquids (RTIL) containing fused
      polycyclic N-alkylisoquinolinium cations ([Cnisoq]+) in combination with the
      bis(perfluoroethylsulfonyl)imide anion ([BETI]-) have been synthesized,
      characterized, and utilized in liquid-liquid partitioning from water; these salts
      have unexpectedly low melting points and give high distribution ratios for
      aromatic solutes, especially chlorobenzenes, between the RTIL and water.

PMID- 12240027
TI  - Synthesis of a new hollandite-type manganese oxide with framework and
      interstitial Cr(III).
AB  - Hollandite with Cr(III) in both tunnel and framework sites has been prepared
      hydrothermally from layered manganese oxide precursors.

PMID- 12240028
TI  - Inducing structural polarity using fluorinated organics: X-ray crystal structures
      of p-XC6F4CN (X = Cl, Br, I).
AB  - Non-centrosymmetric structures are promoted through the use of perfluoroaromatics
      containing structure-directing CN...X (X = Br, I) supramolecular synthons.

PMID- 12240030
TI  - Electro-oxidation of methanol on platinum-organic metal complex mixed catalysts
      in acidic media.
AB  - Novel mixed catalysts systems have been developed using a platinum tetraammine
      complex with a cobalt or nickel quinolyldiamine complex supported on graphite
      powder and heart treated at 600 degrees C in argon atmosphere, for the methanol
      oxidation reaction in direct methanol fuel cells.

PMID- 12240029
TI  - Electrochemistry of chalcogen compounds: prediction of antioxidant activity.
AB  - Synthesis and characterisation of organochalcogens has demonstrated a high
      correlation between their electrochemical oxidation potential on the glassy
      carbon electrode, their activity in bioassays and an unprecedented antioxidant
      activity in neuronal cell culture (EC50 approximately 20 nM) making
      electrochemical methodology a valuable tool in drug design for Alzheimer's and
      related diseases.

PMID- 12240031
TI  - Deep desulfurization of diesel fuel by extraction with ionic liquids.
AB  - A new approach for the deep desulfurization of diesel fuels by extraction with
      ionic liquids is described.

PMID- 12240032
TI  - Design of silica-coated microcapsules for bioencapsulation.
AB  - Alginate-based microcapsules are coated with silica, providing enhanced
      mechanical resistance, protein diffusion and allowing enzyme immobilization.

PMID- 12240033
TI  - Diastereo- and enantioselective synthesis of alpha,beta-disubstituted gamma-nitro
      methyl sulfonates.
AB  - A novel asymmetric synthesis of highly enantioenriched homotaurine precursors has
      been developed via diastereo-selective Michael addition of lithiated enantiopure
      sulfonates to nitroalkenes by using 1,2:5,6-di-O-isopropylidene-alpha-D
      allofuranose as chiral auxiliary.

PMID- 12240035
TI  - Polymer supported chromium porphyrin as catalyst for polycarbonate formation in
      supercritical carbon dioxide.
AB  - A new polymer-supported chromium porphyrin has been prepared and fully
      characterised; its catalytic activity and recyclability were investigated for the
      ring-opening copolymerisation of 1,2-cyclohexene oxide (CHO) and carbon dioxide
      (CO2).

PMID- 12240034
TI  - FRET probes to monitor phospholipase A2 activity.
AB  - Phosphatidylethanolamine and -choline derivatives equipped with fluorescent donor
      acceptor pairs of dyes connected to the tips of the fatty acids were synthesised
      and shown to be suitable substrates for phospholipase A2.

PMID- 12240036
TI  - Intramolecular addition of acyl radicals to alpha-substituted vinylogous
      carbonates: demonstrating the effect of ring size on acyclic stereocontrol.
AB  - The level of stereocontrol obtained in the reduction of the free radical derived
      from the intramolecular addition of an acyl radical to an alpha-branched
      vinylogous carbonate is dependent upon the ring-size of the cyclic ether.

PMID- 12240037
TI  - The promotion of hydrolysis of acetylsalicylic acid in AOT/near-critical propane
      microemulsion.
AB  - A significant acceleration of the hydrolysis of acetylsalicylic acid was
      accomplished by the introduction of an AOT/near-critical propane microemulsion at
      lower W0 values; the rate constant at W0 = 1 was found to be 54 times that in
      aqueous buffer medium in the presence of imidazole catalyst.

PMID- 12240038
TI  - Bimetallic-induced tail-to-tail dimerization and C-H activation of methyl
      acrylate.
AB  - An organometallic complex resulting from tail-to-tail dimerization and C-H
      activation of methyl acrylate (MA), [Mo(CO2Cp(eta 3-(MeO2C)CH[symbol: see
      text]CH[symbol: see text]CHCH2(CO2Me)] 2, has been fully characterized from the
      reaction of the heterobimetallic complex [Cp*Ni=Mo(mu-CO)(CO)2Cp] with MA and an
      exclusively eta 3-allyl bonding mode of the coupled ligand was established for
      the first time by X-ray diffraction; formation of 2 is accompanied by that of the
      mu 3-alkylidyne-capped cluster [NiMo2(mu 3-CCH2CO2Me)(CO)4Cp*Cp2] 3 which results
      from a double C-H activation of the CH2 group of MA; none of these reactions
      occur with the corresponding homodinuclear complexes.

PMID- 12240039
TI  - Efficient heterogeneous catalytic intramolecular Tishchenko reaction of o
      phthalaldehyde to phthalide with alkaline earth oxides.
AB  - The heterogeneous catalytic systems realized by alkaline earth oxides are
      successfully applicable to the highly efficient intramolecular Tishchenko
      lactonization of o-phthalaldehyde to phthalide.

PMID- 12240040
TI  - Thermal stability of an SiO2-coated Rh catalyst and catalytic activity in NO
      reduction by CO.
AB  - An SiO2-coated Rh catalyst with SiO2 thickness of 13 nm has much higher stability
      against sintering of Rh and SiO2 than sol-gel and impregnation Rh/SiO2 catalysts;
      it exhibits the highest activity in the NO-CO reaction among these catalysts
      after thermal treatment.

PMID- 12240041
TI  - A new, highly fluorescent terpyridine which responds to zinc ions with a large
      red-shift in emission.
AB  - A sequence of three metal-catalysed aryl coupling reactions leads to the new
      ligand 4'-(4-N,N-diphenylaminophenyl)-2,2':6',2"-terpyridine, the intense ICT
      emission of which undergoes a large red-shift upon binding of zinc ions,
      providing a unique response over other common metal ions.

PMID- 12240042
TI  - The bond cover approach to chemical topology.
AB  - Bond covers based on substructures can be used to guide retrosynthetic analysis
      and give greater insight into the principle of convergence.

PMID- 12240044
TI  - The stabilisation and reactivity of indium trihydride complexes.
AB  - Indium trihydride complexes were unknown prior to 1998. This article focuses on
      the development of this field over the last 4 years. Emphasis is placed on
      strategies employed to stabilise such complexes, their structure, properties and
      use in inorganic and organic synthesis. Throughout, comparisons are drawn with
      the chemistries of related lighter group 13 metal trihydride complexes. A number
      of similarities and differences have been observed in these comparisons which
      have been rationalised in terms of the properties of the group 13 elements
      involved.

PMID- 12240043
TI  - Preparation of a novel core-shell nanostructured gold colloid-silk fibroin
      bioconjugate by the protein in situ redox technique at room temperature.
AB  - A novel core-shell gold colloid-silk fibroin (SF) bioconjugate was prepared by
      the protein in situ redox technique at room temperature, in which the tyrosine
      (Tyr) residue of the SF, having strong electron donating properties, in situ
      reduced Au(III) ions to Au colloids showing a stable and highly monodispersed
      nature.

PMID- 12240045
TI  - Intramolecular electron conduction along DNA strands and their temperature
      dependency in a DNA-aligned cast film.
AB  - Electroconductivity along a long DNA strand (ca. 10 microns length) in a DNA
      aligned cast film of DNA-lipid complex was measured on a comb-type electrode (5
      microns distance), and it could be reversibly regulated by temperatures across 70
      degrees C.

PMID- 12240046
TI  - Configurational ordering of a cationic dinuclear triple helicate by chiral
      TRISPHAT anions.
AB  - Chiral TRISPHAT anions behave as efficient asymmetric hosts controlling with high
      efficiency the configuration of a cationic dicobalt(II) triple helicate--de up to
      82%.

PMID- 12240047
TI  - Single-source precursors to ternary silver indium sulfide materials.
AB  - Compounds of type [(Ph3P)2AgIn(SC(O)R)4] (R = Me (1), Ph (2)) are excellent
      single-source precursors for AgInS2 bulk materials by pyrolysis and AgIn5S8 films
      by aerosol assisted chemical vapour deposition (AACVD).

PMID- 12240048
TI  - Mesoporous silica-immobilized aluminium chloride as a new catalyst system for the
      isopropylation of naphthalene.
AB  - Mesoporous MCM-41 silica immobilized aluminium chloride shows high catalytic
      activity and selectivity in the Friedel-Crafts alkylation of naphthalene with
      isopropanol.

PMID- 12240049
TI  - Bidentate lactate binding in aqueous solution in a cationic, heptadentate
      lanthanide complex: an effective chiral derivatising agent.
AB  - The X-ray crystal structures of cationic, heptadentate lanthanide complexes of
      holmium and ytterbium bound to lactate are reported and the observed bidentate
      chelation in the solid state is consistent with near-IR CD (Yb) and solution NMR
      measurements; the complexes are shown to act as aqueous chiral derivatising
      agents for alpha-hydroxy acids.

PMID- 12240050
TI  - The first zinc-promoted, environmentally friendly, and highly efficient
      acetoxyallylation of aldehydes in aqueous ammonium chloride.
AB  - An exceptionally mild acetoxyallylation of aldehydes in water promoted by zinc is
      reported, using 3-bromo-1-acetoxyprop-1-ene as starting material; simple
      diastereoselectivity mainly depends on the nature of the aldehyde.

PMID- 12240051
TI  - Layer-by-layer assembly of metal-mediated multiporphyrin arrays.
AB  - Two types of multiporphyrin arrays, mediated by PdCl4(2-) complex ions at the air
      water interface, were alternately transferred onto solid supports to form three
      dimensional organized multilayers by a layer-by-layer method.

PMID- 12240053
TI  - Rhodium catalysed addition of boronic acids to anhydrides: a new method for the
      synthesis of ketones.
AB  - The efficient transmetalation from boron to rhodium is exploited in a new
      synthesis of aryl and alkenyl ketones.

PMID- 12240052
TI  - A novel system consisting of Rh-DuPHOS and ionic liquid for asymmetric
      hydrogenations.
AB  - The ionic liquid [bmim][PF6] was found to provide extra stability to the air
      sensitive chiral catalyst Rh-MeDuPHOS in asymmetric hydrogenation of enamides.

PMID- 12240054
TI  - A convenient imino aldol reaction in ethyl alcohol catalyzed by a cation-exchange
      resin.
AB  - Imino aldol reaction of ketene silyl acetals with imines proceeds smoothly to
      give beta-amino esters in good yields under the influence of a cation-exchange
      resin in ethanol, and the work-up of the reaction consists only of a simple
      filtration followed by concentration of the crude mixture and purification.

PMID- 12240055
TI  - Ferrimagnetic-like ordering in a unique three-dimensional coordination polymer
      featuring mixed azide/carboxylate-bridged trinuclear manganese (II) clusters as
      subunits.
AB  - The crystal structure of the coordination polymer [Mn3(N3)2(nta)4(H2O)2]n (nta =
      nicotinate) consists of trinuclear subunits bridged by mixed mu-1,1-azide and mu
      carboxylate-O,O groups, which are linked by mu 3-nta-N,O,O ligands into a three
      dimensional network exhibiting ferrimagnetic-like ordering.

PMID- 12240056
TI  - Stereospecific oxidation by compound I of cytochrome P450 does not proceed in a
      concerted synchronous manner.
AB  - Calculations show that the transition structure for the synchronous oxygen
      transfer by Compound I is a second order saddle point. The process is unlikely.

PMID- 12240057
TI  - Regioselective cyclization of alpha,omega-alkynoic acids catalysed by TpRu
      complexes: synthesis of endocyclic enol lactones [Tp =
      hydrotris(pyrazolyl)borate].
AB  - The sigma-enynyl complex [TpRu(C(Ph)=C(Ph)C identical to CPh)(P-MeiPr2)]
      efficiently catalyses the regioselective cyclization of alpha,omega-alkynoic
      acids to yield endocyclic enol lactones having ring size up to 12 atoms.

PMID- 12240058
TI  - The tetramethylpiperidinyl-1-oxide anion (TMPO-) as a ligand in lanthanide
      chemistry: synthesis of the per(TMPO-) complex [(ONC5H6Me4)2Sm(mu-ONC5H6Me4)]2.
AB  - (C5Me5)3Sm reacts with the free radical 2,2,6,6-tetramethylpiperidinyl-1-oxy
      (TMPO) to form (C5Me5)2 and the per nitroxide [(eta 1-ONC5H6Me4)2Sm(mu-eta 1:eta
      2-ONC5H6Me4)]2.

PMID- 12240059
TI  - Novel photohydration of non-conjugated aryl/olefin bichromophores within
      cyclodextrin cavities.
AB  - Cyclodextrin media are used to achieve photochemical water addition to isolated,
      acyclic double bonds via intramolecular interaction with excited arenes.

PMID- 12240060
TI  - beta-peptides as catalysts: poly-beta-leucine as a catalyst for the Julia-Colonna
      asymmetric epoxidation of enones.
AB  - Poly-beta-leucines have been evaluated as catalysts for the Julia-Colonna
      asymmetric epoxidation of enones; the beta 3-isomer was found to be an effective
      catalyst for the epoxidation of chalcone (70% ee) and some analogues.

PMID- 12240061
TI  - Reduction of tris(benzene-1,2-dithiolate)molybdenum(VI) by hydroxide ions in dry
      tetrahydrofuran solution.
AB  - Tris(benzene-1,2-dithiolate)molybdenum(VI) reacts rapidly and quantitatively with
      tetrabutylammonium hydroxide to yield the corresponding Mo(V) and Mo(IV)
      complexes and hydrogen peroxide; the reaction has been executed in dry
      tetrahydrofuran where the reaction rate shows a fair dependence on complex and OH
      concentrations.

PMID- 12240063
TI  - Manganese as a template: a new synthesis of corrole.
AB  - The reaction of 2,2'-bisdipyrrins 1, 2, and 3 with manganese(II) acetate
      tetrahydrate and molecular dioxygen yields the manganese(III)corroles 4, 5 and 6,
      which are readily demetalated to the respective free-base corroles.

PMID- 12240062
TI  - Direct oxidation of sulfur-containing fuels in a solid oxide fuel cell.
AB  - Solid-oxide fuel cells with Cu-ceria anodes are shown to provide stable power
      generation through the direct oxidation of hydrocarbon fuels having sulfur levels
      similar to that in gasoline and can be regenerated by steam after being poisoned
      with higher sulfur levels.

PMID- 12240064
TI  - Synthesis and electrochemical properties of novel dimeric fullerenes incorporated
      in a 2,3-diazabicyclo[2.2.2]oct-2-ene framework.
AB  - Novel dimeric fullerenes incorporated in a 2,3-diazabicyclo[2.2.2]oct-2-ene
      framework, with and without direct inter-fullerene-cage bonds, were synthesized
      and fully characterized spectroscopically; the electronic communication between
      the two fullerene cages was clarified by differential pulse voltammetry.

PMID- 12240065
TI  - Chelating alkoxy-N-heterocyclic carbene complexes of silver and copper.
AB  - Incorporation of an alkoxide functional group into an N-heterocyclic carbene
      (NHC) ligand allows the synthesis of the first anionic NHC chelating ligands,
      which react to give the first neutral, molecular silver(I) alkoxide carbene
      complex, and a copper(I) derivative containing the first nonmacrocyclic, square
      planar Cu(I) centres.

PMID- 12240066
TI  - Intercalation and controlled release of pharmaceutically active compounds from a
      layered double hydroxide.
AB  - A series of pharmaceutically active compounds including diclofenac, gemfibrozil,
      ibuprofen, naproxen, 2-propylpentanoic acid, 4-biphenylacetic acid and tolfenamic
      acid can be reversibly intercalated into a layered double hydroxide, initial
      studies suggest that these materials may have application as the basis of a novel
      tuneable drug delivery system.

PMID- 12240067
TI  - Unusual electronic absorption changes in the 800-2200 nm region by intramolecular
      dimer radical cations from photoirradiated meso-2,4-bis[4-(4'
      nitrostyryl)pyridinium]pentane ditetraphenylborates during storage in the dark.
AB  - Electronic absorption spectra were remarkably changed in the broad near-infrared
      region for photoirradiated meso-2,4-bis[4-(4'-nitrostyryl)pyridinium]pentane
      ditetraphenylborates during storage in the dark, which was attributed to
      conformational changes of the intramolecular dimer radical cations between
      sandwich and partially overlapped types.

PMID- 12240068
TI  - Cu4(CH3C(OH)(PO3)2)2(C4H4N2)(H2O)4: a novel, three-dimensional copper
      diphosphonate with metamagnetism.
AB  - A novel, three-dimensional copper diphosphonate
      Cu4(CH3C(OH)(PO3)2)2(C4H4N2)(H2O)4 (1) incorporating an organic pyrazine ligand
      has been hydrothermally synthesized, which exhibits antiferromagnetic ordering
      below 4.2 K and metamagnetic behavior.

PMID- 12240069
TI  - Conjugate addition of arylsilanes to unsaturated carbonyl compounds catalyzed by
      rhodium in air and water.
AB  - ArSiCl3 and Ar2SiCl2, believed to be unstable in aqueous media, reacted
      efficiently with alpha,beta-unsaturated ketones and esters in air and water (in
      the presence of sodium fluoride and a rhodium catalyst), giving good to excellent
      yields of the desired conjugate addition products.

PMID- 12240070
TI  - First chiral selenium ylides used for asymmetric conversion of aldehydes into
      epoxides.
AB  - Enantioenriched selenonium ylides have been generated by addition of benzyl
      bromide to C2 symmetric (2R,5R)-2,5-dimethylselenolane in the presence of NaOH,
      and subsequently reacted with a variety of aldehydes to give oxiranes with
      excellent enantiomeric excesses (a catalytic version has been achieved); also, an
      aliphatic cyclic hypervalent dibromoselenurane structure has been demonstrated by
      X-ray analysis.

PMID- 12240071
TI  - The radical-chain addition of aldehydes to alkenes by the use of N
      hydroxyphthalimide (NHPI) as a polarity-reversal catalyst.
AB  - Hydroacylation of simple alkenes with aldehydes via a radical process was
      successfully achieved by the use of N-hydroxyphthalimide (NHPI) as a polarity
      reversal catalyst. Thus, 5-tridecanone was obtained by the reaction of oct-1-ene
      with pentanal in the presence of small amounts of NHPI and dibenzoyl peroxide
      (BPO).

PMID- 12240072
TI  - The first bismuth phosphonate cluster. X-ray single crystal structure of
      [(ButPO3)10(ButPO3H)2Bi14O(10).3C6H(6).4H2O].
AB  - The reaction of triphenylbismuth and tert-butylphosphonic acid gives the bismuth
      phosphonate phase (ButPO3H)3Bi and the first bismuth phosphonate cluster
      [(ButPO3)10(ButPO3H)2Bi14O(10).3C6H(6).4H2O].

PMID- 12240073
TI  - Two alternative products from the intercalation of alkali metals into cation
      defective Ruddlesden-Popper oxysulfides.
AB  - Sodium may be topotactically inserted into the perovskite layers (under
      thermodynamic control) or the rock-salt layers (under kinetic control) of the
      cation-deficient n = 2 Ruddlesden-Popper oxysulfides Ln2Ti2O5S2 with concomitant
      reduction of TiIV.

PMID- 12240074
TI  - New basic mesoporous silica catalyst obtained by ammonia grafting.
AB  - NH3-treated mesoporous silica (FSM-16) contains SiNH2 sites which exhibit basic
      catalytic activity for Knoevenagel condensation; SiNH2 and SiOH pair sites formed
      at lower NH3-treatment temperatures exhibit higher turnover frequencies (TFs) in
      comparison with SiNH2 single sites.

PMID- 12240075
TI  - Ruthenium-catalysed asymmetric hydrosilylation of ketoximes using chiral
      oxazolinylferrocenylphosphines.
AB  - Chiral ruthenium(II) complexes, RuCl2(PPh3)(oxazolinylferrocenylphosphine), have
      been found to be effective catalysts for asymmetric hydrosilylation of ketoximes
      to give the corresponding primary amines in good yields with high
      enantioselectivities (up to 89% ee) after acid hydrolysis.

PMID- 12240077
TI  - Hydrogen abstraction from ionic liquids by benzophenone triplet excited states.
AB  - The activation energy for hydrogen abstraction from imidazolium-based ionic
      liquids is significantly higher than that observed in conventional solvents.

PMID- 12240076
TI  - Multi-component coupling reactions: synthesis of a guanidine containing analog of
      the hexahydropyrrolo[3,2-c]quinoline alkaloid martinelline.
AB  - A multi-component coupling reaction is used to synthesize a highly functionalized
      guanidine containing pyrroloquinoline analog of martinelline that displays
      bradykinin B2 receptor antagonist activity.

PMID- 12240078
TI  - A by-product using TIPS protection--a warning.
AB  - The TIPS derivatives of alcohols are contaminated with more or less of the
      diisopropyl(n-propyl)silyl derivative, which can be a major product when a bad
      batch of reagent is used, a large excess of reagent is used, and/or the reaction
      is not taken to completion.

PMID- 12240079
TI  - Electronic origin of the structural versatility in linear trichromium complexes
      of dipyridylamide.
AB  - Spin unrestricted DFT calculations on Cr3(dpa)4Cl2 (dpa = dipyridylamide) suggest
      that the linear (Cr3)6+ metal framework could adopt either a symmetric
      conformation, or a strongly nonsymmetric one, depending on the nature of the spin
      coupling between the localized metal electrons.

PMID- 12240080
TI  - Direct electrochemistry of pentachlorophenol hydroxylase.
AB  - The direct electrochemistry of the flavin-containing monooxygenase,
      pentachlorophenol hydroxylase (PCPH), at an edge plane graphite electrode was
      observed and a catalytic response, linear with concentration, was found with the
      substrate pentachlorophenol (PCP).

PMID- 12240081
TI  - Preparation, structure and catalytic properties of a binuclear Pd(0) complex with
      bridging silylene ligands.
AB  - In contrast to the N-heterocyclic carbene (NHC) 1, the homologous N-heterocyclic
      silylene (NHS) 4 acts as a bridging ligand to Pd(0), giving rise to the dinuclear
      complex 5 which is catalytically active in Suzuki reactions.

PMID- 12240083
TI  - Hydrogen-bonded molecular capsules are stable in polar media.
AB  - Robust, very large hydrogen-bonded capsules which are even stable in 50:50 water
      acetone mixtures have been characterized both in solution and in the solid state.

PMID- 12240082
TI  - Hydrogen-bonded capsules in polar, protic solvents.
AB  - A kinetically stable, dimeric capsule is formed by tetrahydroxyresorcinarene in
      methanol; it encapsulates tropylium and tetramethylammonium cations.

PMID- 12240084
TI  - Hydrothermal synthesis of the first organically templated open-framework uranium
      phosphate.
AB  - [(C2H5)2NH2]2[(UO2)5(PO4)4] was prepared from U3O8, HONEt2 and phosphoric acid
      under hydrothermal conditions (180 degrees C, 5 days) and represents the first
      three-dimensional open-framework uranium phosphate prepared to date.

PMID- 12240085
TI  - Hydroxylated nanoballs: synthesis, crystal structure, solubility and
      crystallization on surfaces.
AB  - The reaction of equimolar amounts of Cu(NO3)2 and bdc-5-OH (bdc-5-OH = benzene
      1,3-dicarboxylate-5-hydroxy) affords hydroxylated nanoballs with high solubility
      and an ability to form microcrystals on surfaces.

PMID- 12240086
TI  - M2 delta-to-oxalate pi* conjugation in oxalate-bridged complexes containing M-M
      quadruple bonds.
AB  - The electronic structures of oxalate-bridged, quadruply-bonded dimolybdenum and
      ditungsten compounds have been investigated by a variety of computational methods
      employing density function theory (gradient corrected and time-dependent) which
      reveal the consequences of strong mixing of M2 delta and oxalate pi orbitals
      within extended chains and cyclic structures.

PMID- 12240087
TI  - A new structural motif for rigid C2-symmetrical propeller-shaped 1,2-diamines
      employing double aromatic pi-stacking.
AB  - Utilization of double aromatic pi-stacking interactions on a 2,3-diaminobutane
      framework provides a new motif for structurally rigid C2-symmetrical propeller
      shaped chiral 1,2-diamines.

PMID- 12240088
TI  - Survival and extinction of delocalized ring currents in clamped benzenes.
AB  - Direct visualisation of induced current density in clamped benzenes 1-4
      distinguishes between saturated clamping groups, for which the central benzene
      ring retains a conventional diamagnetic ring current, and strongly interacting,
      unsaturated clamps, for which the central ring supports only the localised
      circulations expected of a 1,3,5-cyclohexatriene with fully fixed double bonds.

PMID- 12240089
TI  - Successive intramolecular transiminations in an iron (II) complex with chiral
      tridentate ligands.
AB  - Two molecules of S-2-pyridylmethylidene-1-(2-pyridyl)ethylamine coordinated to an
      iron(II) undergo successive transiminations yielding bis[1-(2-pyridyl)ethylidene
      2-pyridylmethylamine]iron(II) in acetonitrile.

PMID- 12240090
TI  - Selective binding and reversible release of riboflavin by polymer-bound zinc(II)
      azamacrocycles.
AB  - The reversible formation of a coordinative bond between a polymer-bound Lewis
      acidic metal complex and a flavin imide moiety allows complete extraction of
      riboflavin from aqueous solution at physiological pH and its quantitative release
      at pH 5.

PMID- 12240091
TI  - Inclusion adducts of 4,4-bis(4'-biphenylyl)cyclohexa-2,5-dienone: a clay mimic
      organic host.
AB  - In the lamellar architecture of the title crystal structure mediated by C-H...O
      hydrogen bonds, 1,2-dimethoxyethane and n-hexane are included in the hydrophobic
      galleries; isostructurality of these clathrates is a unique case of guest
      mimicry.

PMID- 12240092
TI  - A novel intramolecular through-space interaction between F and CN: a strategy for
      the conformational control of an acyclic system.
AB  - X-Ray crystallographic analyses of fluorocyanides anti-1 and 2 revealed a novel
      intramolecular through-space interaction between F and CN in an acyclic system,
      which was applied to a stereoselective protonation of acyclic fluorocyanides 2
      having flexible conformation.

PMID- 12240093
TI  - A model complex of a possible intermediate in the mechanism of action of peptide
      deformylase: first example of an (N2S)zinc(II)-formate complex.
AB  - The synthesis and crystallographic characterization of a new (N2S)zinc-alkyl
      complex and (N2S)zinc-formate complex is described; the bonding mode of the
      formate complex has implications for the mechanism of action of the enzyme
      peptide deformylase.

PMID- 12240095
TI  - Recent advances in solventless organic reactions: towards benign synthesis with
      remarkable versatility.
AB  - A paradigm shift away from using solvents in organic synthesis as solventless
      reactions can lead to improved outcomes, and more benign synthetic procedures, in
      for example aldol condensation reactions, sequential aldol and Michael addition
      reactions en route to Krohnke type pyridines, reactions leading to 3
      carboxycoumarins, benzylidenes, 4-aryl-1,4-dihydropyridines and 2-aryl-1,2,3,4
      tetrahydroquinazolines, and oligomerisation reactions for the synthesis of
      cavitands; kinetic considerations for the reaction of two solids can only be
      explained if a eutectic melt is formed during the reaction.

PMID- 12240094
TI  - Sn-MCM-41--a heterogeneous selective catalyst for the Baeyer-Villiger oxidation
      with hydrogen peroxide.
AB  - A new heterogeneous catalyst, Sn-MCM-41, is described for the Baeyer-Villiger
      reaction with hydrogen peroxide which selectively activates the carbonyl function
      for the nucleophilic attack by the oxidant, with high chemoselectivities when
      double bonds are present in the molecule.

PMID- 12240096
TI  - Sustainable metal nano-contacts showing quantized conductance prepared at a gap
      of thin metal wires in solution.
AB  - Sustainable silver and copper nano-contacts showing quantized conductance are
      prepared at a gap between two thin gold wires in solution.

PMID- 12240097
TI  - Heptanuclear hydroxo-bridged copper cluster of the dicubane-like type: structural
      and magnetic characterizations of [Cu7(OH)6Cl2(pn)6(H2O)2](C(CN)3)4Cl2 (pn = 1,3
      diaminopropane).
AB  - A new polynuclear copper(II) complex [Cu7(OH)6Cl2(pn)6(H2O)2](C(CN)3)4Cl2 with
      hydroxo-bridging ligands has been prepared; the centrosymmetric cluster cation
      can be described as two Cu4O3Cl distorted cubane units sharing one copper cation.

PMID- 12240098
TI  - High regioselectivity in propylene hydroformylation using rhodium-bisphosphite
      catalysts is due to properties of the SRS diastereomer.
AB  - The large cone angle and bite angle of the SRS ligand diastereomer in biphenol
      based Rh-bisphosphite catalysts lead to high linear regioselectivity in the
      hydroformylation of propylene.

PMID- 12240099
TI  - An unusual hexanickel cage complex with mu- and mu 3-chloro bridges and an
      interstitial mu 6-chloride.
AB  - A pyrazolate-based dinucleating ligand of the bis(alpha-diimine) type forms an
      unusual hexanucler nickel(II) cage complex incorporating an interstitial mu 6-Cl
      atom.

PMID- 12240100
TI  - Sulfonic acid functionalized mesoporous MCM-41 silica as a convenient catalyst
      for Bisphenol-A synthesis.
AB  - Sulfonic acid groups anchored to the surface of mesoporous MCM-41 silica have
      been identified with S K-edge XANES spectra and the material is an efficient
      catalyst for the liquid phase condensation of phenol with acetone to form
      Bisphenol-A with high selectivity.

PMID- 12240101
TI  - Oxy-function promoted hydroboration of conjugated dienes with controlled allylic
      borane rearrangement.
AB  - Hydroboration of conjugated dienes is promoted by the hydroxy and methoxy groups,
      which also control the rearrangement of the initially produced allylic boranes.

PMID- 12240102
TI  - Spontaneous polymerisation on amphibole asbestos: relevance to asbestos removal.
AB  - Taking advantage of the spontaneous polymerisation of eugenol to lignin-like
      species catalysed by the surface of crocidolite fibres, a procedure is proposed,
      possibly useful in asbestos removal and disposal, where the polymer avoids the
      release of airborne fibres and also scavenges ROS (reactive oxygen species).

PMID- 12240103
TI  - Carbon nanotube template promoted growth of NbS2 nanotubes/nanorods.
AB  - NbS2 nanotubes/rods have been generated successfully employing carbon nanotube
      template promoted growth; high resolution transmission electron microscopy,
      coupled with EDX analysis, confirm the template effect and existence of NbS2 tube
      structures.

PMID- 12240104
TI  - Observation of a P/M interconversion of a gold-phosphine helicate via 31P NMR.
AB  - Ligands containing P-CH2-CH2-P elements have been shown to form double-stranded
      helicates whose axis consists of gold atoms with Au...Au contacts; the
      interconversion of the P and M forms of the helicate [Au3(mu-pp2)2](OTf)3 (pp2 =
      PhP(CH2CH2PPh2)2) is monitored via 31P NMR.

PMID- 12240105
TI  - Blue emission from cysteine ester passivated cadmium sulfide nanoclusters.
AB  - A one-pot synthesis is reported of water-soluble cadmium sulfide nanoclusters
      capped with cysteine ester, with an average size of 2.0 nm and fluorescing in the
      blue region, establishing the possibility of using these as fluorescent
      biological probes.

PMID- 12240106
TI  - Anion directed assembly of a dinuclear double helicate.
AB  - The synthesis and structural characterisation of the diamino-bis-pyridine ligand
      L2 and its diammonium-bispyridinium salt [(H4L2Cl)2].6Cl.H2O 1, are reported; X
      ray diffraction studies reveal that chloride coordination causes the latter to
      adopt a double-helicate structure in the solid-state.

PMID- 12240107
TI  - Conversion of pyrrole to pyrrole-2-carboxylate by cells of Bacillus megaterium in
      supercritical CO2.
AB  - Pyrrole was converted to pyrrole-2-carboxylate in supercritical CO2 using cells
      of Bacillus megaterium PYR 2910, and the yield of the carboxylation reaction in
      supercritical CO2 was 12 times higher than that under atmospheric pressure.

PMID- 12240108
TI  - IR detection of NO2 using p+ porous silicon as a high sensitivity sensor.
AB  - Mesoporous silicon doped with 3.0 x 10(19) B atoms cm-3 (p(+)-type) is an
      insulating material which dramatically increases its electrical conductivity when
      exposed to traces of gaseous NO2; nitrogen dioxide chemisorption at the surface
      generates carriers, the population of which is readily evaluated through the
      intensity of IR absorption.

PMID- 12240109
TI  - Formation and reactivity of a cobalt (II) hydroperoxide intermediate.
AB  - Reaction of Tpt-Bu,MeCo-H with O2 proceeds via a spectroscopically observable
      hydroperoxide whose reactivity in solution and in the solid state differ
      dramatically.

PMID- 12240110
TI  - Placement of cations in NaX faujasite-type zeolite using (N,V,T) Monte Carlo
      simulations.
AB  - The cation distribution in dehydrated NaX was predicted using appropriate
      interatomic potentials and (N,V,T) simulations, considering the cations as
      'guest' particles and the framework as a 'host'; the simulations not only yield
      the expected different types of sites, but also highlight the cooperative
      placement of supercage cations which results essentially from electrostatic
      interactions between the cations.

PMID- 12240111
TI  - Synthesis and oxygenation of selenophosphate dendrimers.
AB  - The backbone of a selenophosphate-based dendrimer of generation 3 having three
      and four carbon chains is flexible enough to allow its chemical modification by
      means of partial or complete oxygenation with bulky peroxide.

PMID- 12240112
TI  - Structural transformations in zopiclone.
AB  - A monoclinic centrosymmetric form of zopiclone dihydrate undergoes a sequential,
      two-step transformation in the solid-state upon heating which results in
      separation of the enantiomers into a racemic conglomerate or racemic twins.

PMID- 12240113
TI  - Pentaporphyrin with flexible, chiral nucleosidic linkers: unexpected duality of
      the physico-chemical properties of its core.
AB  - A new star-like pentaporphyrin, bearing nucleosidic linkers, has been
      synthesized, and the unexpected duality of the physico-chemical properties of its
      core is reported; beside the quenching of the fluorescence of the peripheral
      porphyrins by the central chromophore, this pentaporphyrin exhibits an unexpected
      shielding of the redox capabilities of its central core.

PMID- 12240114
TI  - Synthesis and crystal structure determination of tetramethylammonium auride.
AB  - Tetramethylammonium auride, the first compound of negatively charged gold with a
      non-metal cation, has been synthesised by cation exchange in liquid ammonia; it
      is isostructural to the corresponding bromide which further illustrates the
      similarities between the halogens and gold.

PMID- 12240116
TI  - Colloidal cobalt nanoparticles: a highly active and reusable Pauson-Khand
      catalyst.
AB  - A new Pauson-Khand catalyst based on colloidal cobalt nanoparticles has been
      developed; the catalyst is highly effective for many intra- and inter-molecular
      Pauson-Khand reactions and can be recycled and reused many times without losing
      catalytic activity.

PMID- 12240115
TI  - Multi-component assembly of the bicyclic core associated with the tRNA synthetase
      inhibitors SB-203207 and SB-203208. Application to the synthesis of biologically
      active analogues.
AB  - The ketone (+/-)-5, which embodies the bicyclic core associated with the title
      tRNA synthetase inhibitors 1 and 2, has been prepared via a three-component
      coupling reaction involving 2-(hydroxymethyl)cyclopent-2-enone (15), methylamine
      (6) and propiolamide (10); straightforward elaboration of the readily derived
      acetates (-)-21 and (+)-21 has provided the biologically active analogues 23 and
      24, respectively, of the title compounds.

PMID- 12240117
TI  - Differentiation of mobile and immobile pesticides on anionic clays by 1H HR MAS
      NMR spectroscopy.
AB  - Adsorbed vs. intercalated MCPA (4-chloro-2-methylphenoxyacetic acid) in highly
      hydrated clays taken as a soil model were clearly distinguished by 1H HR MAS NMR;
      adsorbed herbicide gave sharp signals indicating high mobility while intercalated
      herbicide gave very wide unresolved spectra due to its strong interaction with
      the solid matrix.

PMID- 12240118
TI  - Permeability of micelles in surfactant-containing MCM-41 silica as monitored by
      embedded dye molecules.
AB  - Mesoporosu (MCM-41 type) silica containing surfactant-embedded Congo Red has been
      prepared and tested against gas phase HCl and ammonia, as well as solutions of
      ionic species; it is shown that the hybrid (organic-inorganic) material is
      permeable to both gases and ionic species, and can act as a pH indicator and as a
      selective chelating agent.

PMID- 12240119
TI  - Efficient and selective catalytic oxidative cleavage of alpha-hydroxy ketones
      using vanadium-based HPA and dioxygen.
AB  - The combination of H3 + n[PMo12 - nVnO 40].aq (HPA-n, n = 3) and dioxygen proides
      a clean and regioselective reagent for the homolytic cleavage of various
      representative alpha-hydroxy ketones (primaryto tertiary) and turns out to be as
      efficient for the catalytic ring opening of chiral natural products.

PMID- 12240120
TI  - Four- and two-electron rules for diatropic and paratropic ring currents in
      monocyclic pi systems.
AB  - The pi ring current in an even-eletron monocycle is dominated by the HOMO-LUMO
      transition, and hence corresponds to circulation of four electrons in a diatropic
      (4n + 2)-electron, but two in a paratropic (4n)-electron cycle.

PMID- 12240121
TI  - Catalyhtic asymmetric Henry reactions--a simple approach to optically active beta
      nitro alpha-hydroxy esters.
AB  - The development and potential of a catalytic enantioselective Henry reaction of
      nitromethane with various alpha-keto esters catalyzed by chiral bisoxazoline
      copper(II) complexes are presented.

PMID- 12240122
TI  - Unexpected solute aggregation in water on dilution.
AB  - Studies on cluster-cluster aggregation phenomena in aqueous solutions of
      fullerene-cyclodextrin conjugates, beta-cyclodextrin, sodium chloride, sodium
      guanosine monophosphate, and a DNA oligonucleotide revealed that there are larger
      aggregates existent in dilute aqueous solutions than in more concentrated
      solutions.

PMID- 12240123
TI  - A novel, shape-selective, zeolite-catalyzed synthesis of calix(4)pyrroles.
AB  - Porosity and acidity of molecular sieve Al-MCM-41 (ca. 30 A pore diameter) plays
      a crucial role in the synthesis of novel calix(4)pyrroles; for the first time, Al
      MCM-41 has been used as a solid acid catalyst to produce a number of
      calix(4)pyrroles with good selectivity ad yields where zeolite HY (ca. 7.6 A pore
      diameter) yields mainly the linear chain dimer and no cyclic products.

PMID- 12240124
TI  - Highly effective epoxidation of alkenes with Ti-containing soluble polymers.
AB  - Ti-containing polysiloxane epoxidation catalysts have been prepared by controlled
      hydrolysis of titanium- and alkylsilane precursors. These polysilkoxanes exhibit
      very high yields to epoxides in the epoxidation reaction of primary alkenes with
      organic hydroproxides.

PMID- 12240125
TI  - Electrochemical evidence of H' produced by ultrasound.
AB  - Electrochemical evidence of H. produced by cavitation as the result of ultrasonic
      irradiation of an aqueous solution is presented.

PMID- 12240126
TI  - Tuneable electrochemical interactions between polystyrenes with anthracenyl and
      tetrathiafulvalenyl sidechains.
AB  - Polymer 4 and its monomeric counterpart 3 exhibit electrochemically tuneable
      interactions with anthracene polymer 2 and a structurally similar monomer 1 and
      seen by the variation of the oxidation waves of TTF groups and the fluorescence
      of the anthracene.

PMID- 12240127
TI  - Novel spermine-based cationic gemini surfactants for gene delivery.
AB  - Two types of spermine-based gemini surfactants have been synthesised; structure
      activity studies have shown one type to be far superior in gene transection than
      the other.

PMID- 12240128
TI  - MoSe2 and WSe2 nanotubes and related structures.
AB  - MoSe2 and WSe2 nanotubes are obtained by the reduction of the corresponding
      triselenides in hydrogen or by the decomposition of the ammonium selenometallates
      in a hydrogen atmosphere.

PMID- 12240129
TI  - Halogen-free process for the conversion of carbon dioxide to urethanes by
      homogeneous catalysis.
AB  - Carbon dioxide is converted to urethanes (carbamic acid derivatives) through
      reaction with amine and alcohol catalyzed by tin complexes; th addition of
      acetals as a dehydrating agent under high CO2 pressure is the key to achieve high
      yields.

PMID- 12240130
TI  - N-Heterocyclic carbenes can coexist with alkenes and C-H acidic sites.
AB  - The isolation of compounds 3 and 7a,b proves that a singlet carbene center can
      coexist with alkenes or C-H acidic sites in proximity without spontaneous
      annihilation.

PMID- 12240131
TI  - Direct evidence for the incorporation of univalent indium into high-silica
      zeolite, H-ZSM-5, by thermal auto-reductive solid-state ion exchange.
AB  - In mechanical mixtures of H-ZSM-5 and In2O3 thermal auto-reductive solid-state
      ion exchange (AR-SSIE) was found to proceed upon treatment in high vacuum at 840
      K resulting in the incorporation of In+ ions into, and in an increase of the
      thermal stability of, the zeolitic component.

PMID- 12240132
TI  - Room-temperature ionic liquids: a novel versatile lubricant.
AB  - Alkylimidazolium tetrafluoroborates are promising versatile lubricants for the
      contact of steel/steel, steel/aluminium, steel/copper, steel/SiO2, Si3N4/SiO2,
      steel/Si(100), steel/sialon ceramics and Si3N4/sialon ceramics; they show
      excellent friction reduction, antiwear performance and high load-carrying
      capacity.

PMID- 12240133
TI  - [Ni(R2pipdt)2](BF4)2 (R2pipdt = 1,4-disubstituted-piperazine-3,2-dithione) as
      useful precursors of mixed-ligand dithiolenes of interest for non-linear optics.
AB  - A simple method to obtain in high yields mixed-ligand nickel-dithiolene
      complexes, which show strong negative solvatochromism and negative first
      molecular hyperpolarizability, and the use of Raman spectroscopy to establish the
      extent of electronic delocalisation in these complexes, are reported.

PMID- 12240134
TI  - Specific molecular interactions in Pd(II) complexes identify a new approach to
      the biaxial nematic phase.
AB  - Liquid-crystalline complexes of Pd(II) allow a new approach to the realisation of
      the biaxial nematic phase.

PMID- 12240135
TI  - Experimental assessment of lanthanide ion donor preference: spectroscopic and
      theoretical dissection of static charge and dynamic polarisation contributions to
      axial ligation in a C4-symmetric chiral europium complex.
AB  - Measurements of the equilibrium constants for ligand exchange (MeCN, 295 K)
      involving the axial donor in a C4-symmetric, mono-capped, square antiprismatic
      cationic Eu complex, supported by calculations based on an electrostatic
      perturbation model, have been interpreted in terms of a predominant ligand
      polarisation interaction defined by observation of the hypersensitive delta J = 2
      normalised emission intensity, in association with measurements correlating delta
      J = 1 band splitting and 1H NMR dipolar shifts that vindicate Bleaney's theory of
      magnetic anisotropy.

PMID- 12240136
TI  - The nature of the active species in bis(imino)pyridyl cobalt ethylene
      polymerisation catalysts.
AB  - Studies on cobalt ethylene polymerisation catalysts bearing bis(imino)pyridine
      ligands strongly indicate that the activated species is not the anticipated
      cobalt(II) alkyl cation.

PMID- 12240137
TI  - Catalytic C-F activation of polyfluorinated pyridines by nickel-mediated cross
      coupling reactions.
AB  - The cross-coupling reaction of pentafluoropyridine with tributyl(vinyl)tin
      affording 2-vinyltetrafluoropyridine by activation of a carbon-fluorine bond is
      catalysed by [NiF(2-C5NF4)(PEt3)2]; a similar reaction is observed with 2,3,5,6
      tetrafluoropyridine.

PMID- 12240138
TI  - Two different one-dimensional structural motifs in the same coordination polymer:
      a novel interpenetration of infinite ladders by bundles of infinite chains.
AB  - A coordination polymer with a novel structural motif consisting of stacks of
      infinite ladders interpenetrated by bundles of infinite chains is described;
      geometrical arguments are made for the requirements that can lead to such
      interpenetration as a function of ligand dimensions.

PMID- 12240139
TI  - Inorganic-organic interpenetrating frameworks: 4,4'-bipyridine N,N'-dioxide as a
      bridging hydrogen-bond acceptor.
AB  - 4,4'-Bipyridine N,N'-dioxide (L) acts as a hydrogen-bond acceptor in the
      compounds ([M(NO3)2(H2O)4].L2) (M = Co, Ni) to form doubly-interpenetrated
      framework materials with sixfold topological connectivity.

PMID- 12240140
TI  - Hydrogen bond directed formation of liquid-crystalline merocyanine dye
      assemblies.
AB  - Combined interaction of triple hydrogen bonding, dipolar pi-pi aggregation and
      micro-segregation in a melamine-barbituric acid dye assembly leads to a columnar
      mesophase which could be characterized by optical polarising microscopy,
      differential scanning calorimetry and X-ray diffraction.

PMID- 12240141
TI  - 1,3,5-Triarylpent-2-en-1,5-diones for the colorimetric sensing of the mercuric
      cation.
AB  - The 1,3,5-triarylpent-2-en-1,5-dione group selectively undergoes cyclisation and
      changes its colour from yellow to magenta upon coordination of Hg2+ on a remote
      site.

PMID- 12240142
TI  - Synthesis and characterization of [ButNSn(mu-NBut)2TeNBut](mu3-SnTe), a
      stannanetellurone with four-coordinate tin.
AB  - Treatment of [Li2Te(NBut)3]2 with Sn(O3SCF3)2 or SnCl2 in diethyl ether generates
      the stannanetellurone [ButNSn(mu-NBut)2 TeNBut](mu3-SnTe) involving four
      coordinate tin with d(Sn=Te) = 2.589(1) A; the two Sn and two Te atoms are in
      different oxidation states (+II/+IV and +IV/-II, respectively).

PMID- 12240143
TI  - Efficient intramolecular general acid catalysis: a preview from a crystal
      structure.
AB  - The crystal structure of acetal acid 5 reveals changes in geometry representing
      progress along the reaction coordinate for acetal cleavage.

PMID- 12240144
TI  - Novel polymer-supported 2-(diphenylmethylsilyl)ethoxymethyl chloride (DSEM-Cl)
      linker.
AB  - A synthetic method to prepare a novel polymer-supported 2
      (diphenylmethylsilyl)ethoxymethyl chloride (DSEM-Cl) linker and its applications
      are described.

PMID- 12240145
TI  - Control of methanol oxidation by ionic behavior in supercritical water.
AB  - In supercritical water the rate of methanol oxidation was controlled by ionic
      behavior as follows: the oxidation rate of methanol decreased with increasing
      proton and hydroxide ion concentration, possibly due to stabilization of the
      reactant, while that of CO was suppressed by added protons and enhanced by added
      hydroxide ions.

PMID- 12240146
TI  - Reversible trapping of acid and base vapours into an amphoteric crystalline
      material.
AB  - Exposure of the solid zwitterion [CoIII(eta 5-C5H4CO2H)(eta 5-C5H4CO2)] to
      hydrated vapours of volatile acids (HCl, CF3CO2H, HBF4) or bases (NH3, NMe3,
      NH2Me) quantitatively produces the corresponding salts; the heterogeneous
      reactions are fully reversible, as the acid or base molecules can be removed by
      thermal treatment, regenerating the starting material.

PMID- 12240147
TI  - Abnormal binding in a carbene complex formed from an imidazolium salt and a metal
      hydride complex.
AB  - 2-Pyridylmethylimidazolium salts and IrH5(PPh3)2 give an [(N-C)IrH2(PPh3)2]+
      species with the imidazole ring bound in the 'wrong way': at C-5, not at the
      expected C-2.

PMID- 12240148
TI  - p-Sulfonatocalix[6]arene is an effective coacervator of poly(allylamine
      hydrochloride).
AB  - p-Sulfonatocalix[6]arene is shown to form insoluble complexes with
      poly(allylamine hydrochloride) when the charge balance between the negative
      calixarene sulfonate groups matches the positive charge carried by the
      polyelectrolyte, this makes this glycosylaminoglycan analog an interesting
      candidate for controlled release systems in the case of proteins encapsulated in
      mesoscopic complexes with polyelectrolytes.

PMID- 12240149
TI  - Tetra-N-propylammonium perruthenate: a case study in catalyst recovery and re-use
      involving tetraalkylammonium salts.
AB  - The use of tetraalkylammonium salts or imidazolium ionic liquids in catalytic
      oxidations of alcohols with tetra-N-propylammonium perruthenate allows recovery
      and reuse of the oxidant; this concept may find application in the recovery of
      other homogenous catalysts.

PMID- 12240150
TI  - Luminescence and photocatalytic properties of a platinum(II)-quaterpyridine
      complex incorporated in Nafion membrane.
AB  - The non-emissive platinum(II)-quaterpyridine complex shows strong
      photoluminescence at room temperature upon incorporation into Nafion membrane;
      this complex is stabilized toward photochemical decomposition in Nafion even in
      the presence of oxygen, and can be used as a sensitizer to generate singlet
      oxygen to oxidize alkenes.

PMID- 12240151
TI  - Super-microporous organic-integrated silica prepared by non-electrostatic
      surfactant assembly.
AB  - Hybrid organo-silica materials possessing uniform nanoscale porosity in the super
      micropore size range (1.0-2.0 nm diameter) have been prepared using neutral
      alkylamine and non-ionic alkyl(phenyl)polyethylene oxide surfactants as structure
      directing agents.

PMID- 12240152
TI  - Regioselective synthesis of substituted 3,4-dihydro-2H-thiines from alpha,beta
      unsaturated oxathiolanes and styrene derivatives.
AB  - A one-step TiCl4-mediated regiospecific synthesis of thiine derivatives is
      effected in good yields by a tandem cyclisation-fragmentation reaction.

PMID- 12240153
TI  - [(PPh3)Ag(CB11H6Y6)] (Y = H, Br): highly active, selective and recyclable Lewis
      acids for a hetero-Diels-Alder reaction.
AB  - The complex [(PPh3)Ag(CB11H6Br6)] 1 is an effective and selective catalyst (0.1
      mol% loading) for a hetero-Diels-Alder reaction, which shows a marked dependence
      on the presence of trace amounts of water, while addition of Ag[Y] [Y = CB11H12,
      CB11H6Br6, O3SCF3] to a phosphine functionalized support gives an efficient and
      recyclable Lewis acid catalyst for this transformation.

PMID- 12240154
TI  - Novel small organo-P-S/Se heterocycles.
AB  - Oxidative addition of elemental sulfur and selenium to
      cyclomonocarbatetraphosphines (PhP)4CR2 (R = H, Me) afforded novel five- and four
      membered heterocycles PhP(E)CH2PhP(E)E2(E = S, Se) and PhP(Se)CMe2-PhP(Se)Se.

PMID- 12240155
TI  - Catalysis in supercritical CO2 using dendrimer-encapsulated palladium
      nanoparticles.
AB  - Dendrimer-encapsulated nanoparticles are shown to be versatile catalysts for both
      the hydrogenation of styrene and Heck heterocoupling of iodobenzene and
      methacrylate in supercritical CO2 (scCO2).

PMID- 12240156
TI  - Nanoparticles as structural and functional units in surface-confined
      architectures.
AB  - The nanoscale engineering of functional chemical assemblies has attracted recent
      research effort to provide dense information storage, miniaturized sensors,
      efficient energy conversion, light-harvesting, and mechanical motion. Functional
      nanoparticles exhibiting unique photonic, electronic and catalytic properties
      provide invaluable building blocks for such nanoengineered architectures. Metal
      nanoparticle arrays crosslinked by molecular receptor units on electrodes act as
      selective sensing interfaces with controlled porosity and tunable sensitivity.
      Photosensitizer/electron-acceptor bridged arrays of Au-nanoparticles on
      conductive supports act as photoelectrochemically active electrodes.
      Semiconductor nanoparticle composites on surfaces act as efficient light
      collecting systems, and nanoengineered semiconductor 'core-shell' nanocrystal
      assemblies reveal enhanced photoelectrochemical performance due to effective
      charge separation. Layered metal and semiconductor nanoparticle arrays
      crosslinked by nucleic acids find applications in the optical, electronic and
      photoelectrochemical detection of DNA. Metal and semiconductor nanoparticles
      assembled on DNA templates may be used to generate complex electronic circuitry.
      Nanoparticles incorporated in hydrogel matrices yield new composite materials
      with novel magnetic, optical and electronic properties.

PMID- 12240157
TI  - Effect of phthalates on the stability and performance of AgBF4-PVP membranes for
      olefin/paraffin separation.
AB  - The presence of a phthalate in dry polymer membranes consisting of
      polyvinylpyrrolidone (PVP) and AgBF4, AgBF4-PVP, provides long-term stability and
      better performance for the separation of propylene/propane gas mixtures.

PMID- 12240158
TI  - A high coking-resistance catalyst for methane aromatization.
AB  - Steaming-dealuminated HZSM-5-supported molybdenum catalysts have been found to be
      high coking-resistance catalysts for methane aromatization reactions; compared
      with conventional catalysts, they give a much higher selectivity towards
      aromatics.

PMID- 12240160
TI  - (eta 5-Cyclopentadienyl)(kappa 3-hydrotris(pyrazolyl)borate)cobalt(II)--the first
      high-spin cobalt organometallic complex.
AB  - (eta 5-Cyclopentadienyl)(kappa 3-hydrotris(pyrazolyl)borate)-cobalt(II) has been
      synthesised; magnetic and crystallographic data indicate this to be the first
      example of a high-spin cobalt organometallic complex whilst its
      pentamethylcyclopentadienyl analogue is found to have a low-spin electronic
      configuration.

PMID- 12240159
TI  - Sequence fidelity of a template-directed PNA-ligation reaction.
AB  - The ligation method and an appended duplex-stabilizing dye affect both yield and
      sequence selectivity of a template-controlled PNA-ligation. The highest
      selectivity was obtained with a peptide condensation that formed an abasic site.

PMID- 12240161
TI  - Diastereoselectivity controlled by electrostatic repulsion between the negative
      charge on a trifluoromethyl group and that on aromatic rings.
AB  - Intramolecular electrostatic repulsions between the local negative charge on a
      trifluoromethyl group and that on the ortho position of an aryl moiety of a
      nucleophile was found to be a controlling factor of the diastereoselectivity in a
      cyclopropanation reaction, in which the electrostatic repulsion was evaluated
      quantitatively.

PMID- 12240162
TI  - Extreme (10(9)) acidification of adenine-NH2 in an open platinated nucleobase
      quartet. A pH switch with potential as a biological acid/base catalyst.
AB  - The combination of electronic effects (PtII binding to N7 and N1) and a
      favourable conformation permitting efficient stabilization of the anion brings
      about a 10(9) fold increase in the exocyclic amino group acidity of 9
      ethyladenine.

PMID- 12240163
TI  - A one step process for grafting organic pendants on alumina via the reaction of
      alumina and phosphonate under microwave irradiation.
AB  - Phosphonate esters react with gamma-alumina under microwave (MW) irradiation;
      this reaction is a simple preparative method to graft organic pendant groups onto
      the surface of alumina; the efficiency of the grafting was readily checked by
      solid-state NMR techniques (31P and 27Al).

PMID- 12240164
TI  - Steric acceleration of an uncatalysed ene reaction at room temperature.
AB  - The bulky trityl steric buttress is used to effect an intramolecular, uncatalysed
      ene reaction that operates at room temperature, whilst smaller buttresses require
      heat.

PMID- 12240165
TI  - The first Ru(II)-catalysed asymmetric hydrogen transfer reduction of aromatic
      ketones in aqueous media.
AB  - The first water-soluble asymmetric hydrogen-transfer ruthenium(II) catalyst
      system consisting of [Ru(p-cymene)Cl2]2, (S)-proline amide, and sodium formate,
      which gives high conversion rates with high ee values up to 95.3% and is
      reusable, has been developed.

PMID- 12240166
TI  - Organocatalytic chain scission of poly(lactides): a general route to controlled
      molecular weight, functionality and macromolecular architecture.
AB  - A facile, single-step transesterification approach to poly(lactides) with
      controlled molecular weights and end-group functionality, as well as block and
      star-shaped architectures is described using nucleophilic amine catalysts.

PMID- 12240167
TI  - Stereoselective preparation of highly functionalized (Z)-3-magnesiated enoates by
      an iodine-magnesium exchange reaction.
AB  - 3-Iodoenoates are converted into the corresponding alkenylmagnesium species with
      complete retention of configuration of the double bond; both direct reaction and
      copper(I)-mediated reactions with various electrophiles provide polyfunctional
      enoates.

PMID- 12240168
TI  - Solvation of 1-butyl-3-methylimidazolium hexafluorophosphate in aqueous ethanol-
      a green solution for dissolving 'hydrophobic' ionic liquids.
AB  - The relatively hydrophobic ionic liquid 1-butyl-3-methylimidazolium
      hexafluorophosphate has been found to be totally miscible with aqueous ethanol
      between 0.5 and 0.9 mol fraction ethanol, whereas the ionic liquid is only
      partially miscible with either pure water or absolute ethanol; the ability to
      dissolve 1-butyl-3-methylimidazolium hexafluorophosphate in a 'green' aqueous
      solvent system has important implications for cleaning, purification, and
      separations using ionic liquids.

PMID- 12240169
TI  - Discotic mesogens with potential electron carrier properties.
AB  - A new family of discotic liquid crystals, potentially electron carriers, has been
      synthesised, some members of which exhibit a particularly rich thermotropic
      behaviour.

PMID- 12240170
TI  - Directed and undirected asymmetric dihydroxylation reactions: application in the
      synthesis of a C-linked analogue of allolactose.
AB  - The complex OsO4.(S,S)-1,2-diphenyl-N,N'-bis(2,4,6-trimethylbenzyl)ethane-1,2
      diamine is an effective reagent for the desymmetrisation of meso-1,2-bis(3,6
      dihydro-2H-pyran-2-yl)ethanes by asymmetric dihydroxylation; this process, whose
      sense of diastereoselectivity depends on substitution and stereochemistry, has
      been exploited in the synthesis of a C-linked analogue of allolactose.

PMID- 12240171
TI  - The regioselective aminohydroxylation of allylic carbamates.
AB  - The synthesis and aminohydroxylation of a series of acyclic allylic carbamates is
      described: the formation of a putative O=Os=NR linkage between the transition
      metal and substrate is proposed to account for the high levels of
      regioselectivity that were observed; proof of the structure of one of the
      aminohydroxylation products was obtained through X-ray crystallography.

PMID- 12240172
TI  - The synthesis and solid state structure of (8S)-8-benzyl-8,9-dihydro-7H
      tetrazolo[1,5-d][1,4]diazepin-6-one.
AB  - An unusual tetrazolodiazepin-6-one was prepared and shown, by X-ray
      crystallography, to adopt an essentially planar conformation about the tetrazole
      ring with geometry that closely approximates a cis-amide bond.

PMID- 12240174
TI  - A new practical ketone synthesis directly from carboxylic acids: first
      application of coupling reagents in palladium catalysis.
AB  - A new palladium-catalyzed cross-coupling reaction between arylboronic acids and
      carboxylic acids, activated in situ for the oxidative addition to a
      tricyclohexylphosphine palladium(0) catalyst by treatment with di(N-succinimidyl)
      carbonate (DSC) is disclosed, which allows the high-yielding synthesis of various
      functionalized arylketones under mild conditions.

PMID- 12240175
TI  - S3O, a new sulfur oxide identified in the gas phase.
AB  - S3O, a novel, linear sulfur oxide has been detected in the gas phase by means of
      neutralization reionization mass spectrometry; the upper limit of stability of
      acyclic forms of SnO oxides has been set by theoretical calculations.

PMID- 12240173
TI  - Synthesis and properties of fac-Re(dmbpy)(CO)3CHO (dmbpy = 4,4'-dimethyl-2,2'
      bipyridine), a possible intermediate in reductions of CO2 catalyzed by fac
      Re(dmbpy)(CO)3Cl.
AB  - Synthesis of fac-Re(dmbpy)(CO)3CHO 2 and its reactions with CO2 in DMF and DMSO
      have been conducted; 2 transfers hydride to CO2 to give Re(dmbpy)(CO)4+ OCHO- 5
      which is rapidly transformed to fac-Re(dmbpy)(CO)3(OCHO) 3 in DMF, thus
      supporting the viability of 2 in photocatalytic reactions of fac-Re(dmbpy)(CO)3Cl
      with CO2.

PMID- 12240176
TI  - Interaction-induced enhancement in the activity and selectivity of a titania
      supported ammonium salt of a 12-molybdophosphoric acid catalyst during
      ammoxidation of 2-methylpyrazine.
AB  - A titania-supported ammonium salt of 12-molybdophosphoric acid has been
      synthesized, and the salt-support interaction, which enhanced the reaction rate,
      has been correlated with the activity of the catalyst in the ammoxidation of 2
      methylpyrazine.

PMID- 12240177
TI  - A silver-containing halogen-free inorganic photochromic glass.
AB  - A halogen-free inorganic photochromic soda-lime silicate glass containing silver
      ions has been developed; reversible change between colorless and yellow color in
      this glass is achieved through combined 193 nm excimer laser irradiation and heat
      treatment.

PMID- 12240178
TI  - New fluorescent probes for the detection of mixed sodium and potassium metal
      ions.
AB  - A new fluorescent probe 2 is developed that is capable of measuring the
      concentration of a mixture of sodium and potassium ions in the solution. This
      probe contains a fluorophore that is utilized in two ways depending on the pH of
      the solution.

PMID- 12240179
TI  - Monomeric uni-ligated aluminates.
AB  - The tetradentate ligand, common name Salban(But)H4 (N,N'-bis(2-hydroxy-3,5-di
      tert-butylbenzyl)-1,4-diaminobutane) combines with appropriate amounts of LiAlH4
      to produce the unique monomeric, uni-ligated aluminate [Salban(But)Al]Li(thf)2
      (1) and the bimetallic derivative Salban(But)(AlH2Li(thf)2)2 (2).

PMID- 12240180
TI  - The first isolable pentacoordinate 1,2 lambda 5-azaphosphetine: synthesis, X-ray
      crystallographic analysis, and dynamic behaviour.
AB  - Cycloaddition reaction of an iminophosphorane bearing the Martin ligand with an
      alkyne gave the first stable 1,2 lambda 5-azaphosphetine, whose structure was
      determined by X-ray crystallographic analysis, and variable temperature NMR
      spectroscopy revealed the existence of equilibrium with the corresponding alpha
      iminoalkylidenephosphorane.

PMID- 12240181
TI  - Enhanced acid stability of a reduced nicotinamide adenine dinucleotide (NADH)
      analogue.
AB  - A methyl substituent at C-5 of the nicotinamide ring is found to confer increased
      acid stability in a reduced nicotinamide model (5-20 fold) and in a reduced
      dinucleotide coenzyme (2-3 fold), while retaining reactivity towards hydride
      transfer.

PMID- 12240182
TI  - Porous clay heterostructures with enhanced acidity obtained from acid-activated
      clays.
AB  - Porous clay heterostructures (PCHs) with enhanced acidity may be prepared from
      suitably acid-activated montmorillonite clays; the higher acidity arises from
      Bronsted acid sites generated by acid treatment of the clay prior to its use as a
      host for PCH formation.

PMID- 12240184
TI  - Triprotic 2,4,6-tris(organoamino)-1,3,5-triazenes as precursors to multi-site
      triazenate ligands.
AB  - 2,4,6-Tris(2-fluoroanilino)-1,3,5-triazene successively undergoes one-, two- and
      three-fold deprotonation in the presence of BunLi; the dilithiated triazenate
      exists as the dimeric complex (thf)6Li4[(RN)2(RNH)C3N3]2 in the solid state (R =
      2-F-C6H4) featuring bidentate Nendo-C-Nexo chelation sites.

PMID- 12240183
TI  - Alkane oxidation by a carboxylate-bridged dimanganese(III) complex.
AB  - A new manganese(II) oxamato dimer possesing an unprecedented Mn2(mu-O2CR)(mu
      OH2...O2CR) core has been synthesised, structurally and magnetically
      characterised, and used as a catalyst for the oxidation of alkanes to alcohols
      and ketones by ButO2H and O2 in CH2Cl2 at rt.

PMID- 12240185
TI  - First molecular switch encapsulated within the cavities of a zeolite. A dramatic
      lifetime increase of the charge-separated state.
AB  - A [2]-catenane consisting of a bipyridinium cyclophane and a dioxybenzene
      macrocyclic polyether has been encapsulated within the supercages of zeolite Y by
      ship-in-a-bottle synthesis; laser flash photolysis reveals that the charge
      separated species decays in hundreds of microseconds in contrast to the few
      picoseconds previously reported for the same transient in acetonitrile.

PMID- 12240186
TI  - The significance of proton migration during hole hopping through DNA.
AB  - Hole transfer through DNA is coupled with proton transfer processes.

PMID- 12240187
TI  - Synthesis and reactivity of an efficient 1,2-dehydrocarborane precursor, phenyl[o
      (trimethylsilyl)carboranyl]iodonium acetate.
AB  - The reaction of [o-(trimethylsilyl)carboranyl]lithium with IPh(OAc)2 in diethyl
      ether affords an efficient 1,2-dehydro-o-carborane precursor 4: the facile 2 + 4
      cycloaddition of 4 with dienes in the presence of the desilylating agent is
      reported.

PMID- 12240188
TI  - Evidence of 29Si NMR paramagnetic shifts in rare-earth zeolite LSX.
AB  - Paramagnetic shifts have been observed for the first time in rare-earth zeolites;
      the 29Si MAS NMR spectra of rare-earth ion-exchanged low silica X show a large
      range of isotropic chemical shifts that can be attributed to Fermi contact
      interactions with the lanthanide electronic moments.

PMID- 12240189
TI  - Universal hybridization using LNA (locked nucleic acid) containing a novel pyrene
      LNA nucleotide monomer.
AB  - A novel pyrene LNA nucleotide monomer is shown to mediate universal hybridization
      when incorporated into a DNA strand or a 2'-OMe-RNA/LNA chimeric strand. For the
      latter, high-affinity universal hybridization without compromising the base
      pairing selectivity of bases neighbouring the universal pyrene LNA nucleotide
      monomer is documented.

PMID- 12240190
TI  - Characterization of an oxaluric acid derivative as a guanine oxidation product.
AB  - The oxidation of guanine in the dinucleoside monophosphate d(GpT) by an oxo
      metalloporphyrin generates a linear oxaluric acid derivative after heating at 65
      degrees C for 30 min and at neutral pH.

PMID- 12240191
TI  - Single crystal particles of a mesoporous mixed transition metal oxide with a
      wormhole structure.
AB  - A new type of mesoporous mixed transition metal oxide of Nb and Ta (NbTa-TIT-1)
      has been prepared through a two-step calcination, which consists of single
      crystal particles with wormhole mesoporous structure.

PMID- 12240192
TI  - Living polymerization and block copolymerization of alpha-olefins by an amine
      bis(phenolate) titanium catalyst.
AB  - An amine bis(phenolate) dibenzyl titanium complex having a methoxy donor on a
      side arm leads, upon activation with tris(pentafluorophenyl)borane, to unique
      living properties in alpha-olefin polymerization: exceptionally high molecular
      weight poly(1-hexene) is obtained in a living fashion at room temperature, living
      polymerization of 1-hexene is obtained above room temperature, and block
      copolymerization of 1-hexene and 1-octene at room temperature is described as
      well.

PMID- 12240193
TI  - Simultaneous combination of in situ-EPR/UV-VIS/on line GC: a novel setup for
      investigating transition metal oxide catalysts under working conditions.
AB  - In situ-EPR, in situ-UV-VIS spectroscopy and on line-GC have been for the first
      time simultaneously combined to follow the behaviour of lanthanum-doped CrOx/ZrO2
      and CrOx/Al2O3 catalysts during the dehydrogenation of propane to propene.

PMID- 12240194
TI  - Ion-exchange as a mode of cation transfer into room-temperature ionic liquids
      containing crown ethers: implications for the 'greenness' of ionic liquids as
      diluents in liquid-liquid extraction.
AB  - The transfer of strontium ion from acidic nitrate media into a series of 1-alkyl
      3-methylimidazolium-based room-temperature ionic liquids containing dicyclohexano
      18-crown-6 is shown to proceed via cation-exchange, in contrast to conventional
      solvents such as alkan-1-ols, in which extraction of a strontium nitrato-crown
      ether complex is observed.

PMID- 12240195
TI  - Mimicking oxide surfaces: different types of defects and ligand coordination at
      well defined positions of a molybdenum oxide based nanocluster.
AB  - The mixed valence cluster anion of the compound
      (NH4)32[MoVI110MoV28O416H6(H2O)58(CH3CO2)6].xH2O 1 (x approximately 250),
      synthesized under one-pot conditions, contains well-defined different types of
      defects--missing groups compared to the complete parent (Mo154) type cluster with
      full D7d symmetry--and acetate ligand coordination; this proves that the giant
      wheel type anion can be considered as an object with a variety of nanoscale
      structural features ("nanostructured landscape") allowing reactions at a variety
      of well defined centers.

PMID- 12240196
TI  - Tunable clathrates.
AB  - Investigation of the selectivity of a diol organic host for mixtures of DMF and
      DMSO, showed the formation of five inclusion compounds in which the stoichiometry
      varies in discrete steps and is determined by the composition of the liquid guest
      mixture; the structures of these compounds are described.

PMID- 12240197
TI  - Shape-selective photocatalytic transformation of phenols in an aqueous medium.
AB  - A zeolitic material containing Ti chains activated by light allows a shape
      selective transformation of organic compounds; the molecules that can enter into
      the zeolitic cavities are protected from the light-induced processes, while the
      other are degraded.

PMID- 12240198
TI  - Site effects in controlling the chemical reactivity in crystals: solid-state
      photochromism of N-(n-propyl)nitrospiropyrane.
AB  - The dynamics of decay of the photoproducts of the two non equivalent molecules of
      N-(n-propyl) nitrospiropyrane in the crystalline state is significantly different
      due to the effect of the specific site where each of the molecules is located in
      the crystal latice.

PMID- 12240199
TI  - A polymeric sodium complex of 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine.
AB  - The ligand 3,6-bis(2-pyridyl)-1,2,4,5-tetrazine forms a 1:1 complex with
      Na[BPh4], which has been structurally characterised as a one-dimensional
      polymeric system with an unusual coordination geometry about the sodium.

PMID- 12240200
TI  - Structural characterisation of the H-bonded [MnII(OH2)2...(OCH3)2MnIII] motif: a
      model for resting state hydroxylic solvent coordination in M(II)-M(III) enzymes.
AB  - A mixed-valence dimanganese complex with two water ligands bound to the Mn(II)
      ion and two methoxide ligands bound to the Mn(III) ion in a H-bonded arrangement
      has been structurally characterised and models possible resting state
      water/hydroxide coordination in purple acid phosphatases.

PMID- 12240202
TI  - Biaxial smectic A liquid crystal in a pure compound.
AB  - The synthesis and characterisation is reported of a low molecular weight organic
      compound to exhibit the biaxial smectic A (SmAb) phase, which shows a transition
      from the partial bilayer uniaxial SmAd phase to the SmAdb phase as the
      temperature is lowered.

PMID- 12240201
TI  - The first structurally characterised homoleptic organovanadium(III) compound.
AB  - The homoleptic, tetrahedral, paramagnetic d2 species [NBu4][VIII(C6Cl5)4] 1 has
      been obtained and characterised by analytical, spectroscopic and X-ray
      diffraction methods.

PMID- 12240203
TI  - Photosensitization of nanocrystalline TiO2 films by pomegranate pigments with
      unusually high efficiency in aqueous medium.
AB  - An aqueous system based on a TiO2 layer photosensitized by natural pigment(s)
      from pomegranate, shows relatively high stability under illumination with a
      quantum yield of 0.74 and a photovoltage of 0.46 V.

PMID- 12240204
TI  - New binucleating ligands to support dizirconium organometallics.
AB  - A new class of bis(amidinato) ligands, which feature dibenzofuran or 9,9
      dimethylxanthene spacers, are used to prepare structurally characterized
      dizirconium complexes.

PMID- 12240205
TI  - A new pathway in the reaction of disilene with carbonyl compounds: an 'ene'
      reaction instead of cycloaddition.
AB  - The 3H-disilagermirene, (tBu2MeSi)4GeSi2, reacts with alpha-hydrogen containing
      carbonyl compounds (acetophenone, butane-2,3-dione) by an 'ene'-reaction pathway
      followed by isomerization or insertion reactions, representing a new mode in the
      reaction of disilenes with carbonyl compounds.

PMID- 12240207
TI  - A bis-bidentate dioxolene ligand induces thermal hysteresis in valence
      tautomerism interconversion processes.
AB  - The use of a bis-bidentate ligand in a solid cobalt dioxolene complex affords the
      necessary cooperative properties that lead to thermal hysteresis in a valence
      tautomeric interconversion equilibrium.

PMID- 12240206
TI  - Characterization of germanium site distribution in zeolite ITQ-7 by
      photoluminescence.
AB  - Zeolite ITQ-7 containing germanium emits luminescence upon excitation at the
      wavelength of the absorption maxima; control experiments with amorphous GeO2 and
      all-silica zeolites indicate that the emission is attributable to Ge atoms
      occupying framework positions; the emission decays on the nanosecond time scale
      and it fits to variable proportions of three exponential kinetics, this being
      compatible with the presence of three families of Ge atoms in the solid.

PMID- 12240208
TI  - A homoleptic phosphine adduct of Tl(I).
AB  - A homoleptic phosphine adduct of thallium(I) supported by a tris(phosphino)borate
      ligand has been isolated and structurally characterized.

PMID- 12240209
TI  - Revision of the absolute configuration of the tricyclic sesquiterpene (+)
      kelsoene by chemical correlation and enantiospecific total synthesis of its
      enantiomer.
AB  - The absolute configuration of the recently identified sesquiterpene (+)-kelsoene
      was revised by chemical correlation with (R)-(+)-pulegone; the correct structure
      is (1R,2S,5R,6R,7R,8S)-2,8-dimethyl-6-(1-methylethenyl)tricyclo[5.3.0.0
      (2,5)]decane.

PMID- 12240210
TI  - Biosynthesis of the vancomycin group of antibiotics: characterisation of a type
      III polyketide synthase in the pathway to (S)-3,5-dihydroxyphenylglycine.
AB  - 3,5-dihydroxyphenylacetate, a precursor for the non-proteinogenic amino acid 3,5
      dihydroxyphenylglycine occurring in glycopeptide antibiotics, is determined to be
      catalysed by a type III polyketide synthase using malonyl-CoA as a starter unit.

PMID- 12240211
TI  - Protein-based materials, toward a new level of structural control.
AB  - Through billions of years of evolution nature has created and refined structural
      proteins for a wide variety of specific purposes. Amino acid sequences and their
      associated folding patterns combine to create elastic, rigid or tough materials.
      In many respects, nature's intricately designed products provide challenging
      examples for materials scientists, but translation of natural structural concepts
      into bio-inspired materials requires a level of control of macromolecular
      architecture far higher than that afforded by conventional polymerization
      processes. An increasingly important approach to this problem has been to use
      biological systems for production of materials. Through protein engineering,
      artificial genes can be developed that encode protein-based materials with
      desired features. Structural elements found in nature, such as beta-sheets and
      alpha-helices, can be combined with great flexibility, and can be outfitted with
      functional elements such as cell binding sites or enzymatic domains. The
      possibility of incorporating non-natural amino acids increases the versatility of
      protein engineering still further. It is expected that such methods will have
      large impact in the field of materials science, and especially in biomedical
      materials science, in the future.

PMID- 12240212
TI  - Self-assembled monolayers of new dendron-thiols: manipulation of the patterned
      surface and wetting properties.
AB  - SAMs based on a novel dendron-thiol system, which maintain the alkanethiols'
      active site, but with the -SH group connected to independently variable groups by
      a dendron-linker, showed a controllable surface pattern and wetting properties.
      The precisely tailored structure of dendron-thiols with locally controlled
      hydrophobic and hydrophilic peripheries allows the formation of designed surface
      structures on a gold surface, e.g. nano-stripes, honeycomb and homogeneous
      structures.

PMID- 12240214
TI  - Molybdenum-catalyzed episulfidation of (E)-cycloalkenes with elemental sulfur.
AB  - Episulfidation of (E)-cyclooctene and (E)-cyclononene was achieved with elemental
      sulfur by using a catalytic amount of a molybdenum oxo complex.

PMID- 12240213
TI  - Ready protease-catalyzed synthesis of carbohydrate-amino acid conjugates.
AB  - The protease-catalyzed synthesis of amino acid est-carbohydrate conjugates as
      glycopeptide analogues has been achieved in a highly regioselective and
      carbohydrate-specific manner using amino acid vinyl ester acyl donors and
      minimally or completely unprotected carbohydrate acyl acceptors, which together
      probed active sites of proteases to reveal yield efficiencies that are modulated
      by the carbohydrate C-2 substitutent, and that may be exploited to allow
      selective one-pot syntheses.

PMID- 12240215
TI  - The preparation of organically functionalized chromium and nickel nanoparticles.
AB  - Nanoparticles of chromium or nickel have been prepared by the reduction of either
      CrCl2 or Ni(acac)2 (acac = pentane-2,4-dionate) at elevated temperatures in
      various Lewis base solvents; the effect of the Lewis base, which acts as both a
      reaction solvent and passivating ligand on morphology are apparent; the
      nanostructures have been analysed by NMR, IR, TEM and XRD.

PMID- 12240216
TI  - Synthesis and photophysical properties of [3.3](3,9)carbazolophanes.
AB  - Syn- And anti-[3.3](3,9)carbazolophanes, which are suitable model compounds for
      sandwich and partial-overlap excimers, respectively, have been synthesized and
      characterized; the structures of both singlet and triplet carbazole excimer have
      been described.

PMID- 12240217
TI  - A green Hunsdiecker reaction: synthesis of beta-bromostyrenes from the reaction
      of alpha,beta-unsaturated aromatic carboxylic acids with KBr and H2O2 catalysed
      by Na2MoO4.2H2O in aqueous medium.
AB  - Reaction of alpha,beta-unsaturated aromatic carboxylic acids with KBr and H2O2 in
      the presence of Na2MoO4.2H2O in aqueous medium affords beta-bromo alkenes in high
      yield.

PMID- 12240218
TI  - Site-selectivity in a heterotetranuclear macrocyclic complex.
AB  - Site-selectivity in a heterotetranuclear macrocylic complex is controlled by the
      geometry of the dinuclear intermediate.

PMID- 12240219
TI  - Directly linked dehydropurpurin-porphyrin dyads from Ag(I)-promoted oxidation of
      meso-phenylethynyl substituted zinc(II) porphyrins.
AB  - Ag(I)-promoted oxidation of (5,15-diaryl-10-phenylethynyl-porphyrinato)zinc(II)
      complexes in CHCl3 gave directly linked 12,13-dehydropurpurin-porphyrin dyads,
      the structures of which were revealed by X-ray analysis.

PMID- 12240220
TI  - Steric effects on the mode of aggregation and reactivity of clusters formed from
      the lithiation of trisamidothiophosphates.
AB  - Lithiation of SP[N(H)R]3 with LiBun produces the dimers [(THF)LiSP(NR)(NHR)2]2 (R
      = Pri) or ([LiSP(NR)-(NHR)2][(THF)LiSP(NR)2(NHR)])2 (R = But) with central Li2N2
      or Li2S2 rings, respectively; further lithiation yields the dianion
      [SP(NR)2(NHR)]2- (R = Pri) or leads to sulfur extrusion when R = But.

PMID- 12240221
TI  - Bis[(alkoxy)benzoylsemicarbazides]--a new class of powerful organogelators.
AB  - Reaction of N-[(alkoxy)benzoyl]hydrazides and diisocyanates produces
      bis[(alkoxy)benzoylsemicarbazides] that allow for 'cold gelation' of organic
      liquids by mixing low viscous gelator solutions with a large excess of the
      respective solvent at ambient temperature.

PMID- 12240222
TI  - Transition metal-catalysed acylation of alpha,beta-unsaturated carbonyl compounds
      with acylstannanes.
AB  - Acylstannanes were found to add to such alpha,beta-unsaturated carbonyl compounds
      as enones or ynoates in the presence of a nicel or palladium catalyst to give 2
      stannyl-4-oxoalk-2-enoates or 1,4-diketones, whereas the three component coupling
      between acylstannanes, enones and aldehydes provided 2-hydroxymethyl 1,4
      diketones.

PMID- 12240223
TI  - Hierarchic patterning: architectures beyond 'giant molecular wheels'.
AB  - Based on symmetry breaking steps under one-pot conditions, simple molybdenum
      oxide-based building blocks initially assemble to 'giant molecular wheels' in a
      fast process followed by further slower assembly processes leading stepwise to
      more complex mesoscopic architectures including spherical ones and finally to
      those with a size larger than 500 nm.

PMID- 12240224
TI  - Inorganic-organic hybrids derived from oxovanadium sulfate motifs: synthesis and
      characterization of [VIVO(mu 3-SO4)(2,2'-bpy)]infinity.
AB  - The hydrothermal reaction of V2O5, V2O3, 2,2'-bpy and Na2SO4 in dilute sulfuric
      acid yields a novel hybrid, [VIVO(mu 3-SO4)(2,2'-bpy)]infinity, which
      demonstrates the potential of constructing a new class of robust composite solids
      composed of a (V/O/SO4)-based framework decorated with organic functionalities by
      combining appropriate vanadyl sulfate motifs with a variety of organic ligands.

PMID- 12240225
TI  - Stereoselective total synthesis of (+)-myriocin from D-mannose.
AB  - The stereoselective total synthesis of myriocin 1 from D-mannose is described;
      the carbon framework with three contiguous chiral centers including a tetra
      substituted carbon with nitrogen was effectively constructed using Overman
      rearrangement as the key reaction.

PMID- 12240226
TI  - Synthesis of the marine natural product barbamide.
AB  - The first total synthesis of the trichlorinated natural product barbamide is
      described. The convergent approach involves coupling (S)-3
      trichloromethylbutanoyl chloride with Meldrum's acid (2,2-dimethyl-1,3-dioxane
      4,6-dione) to give 15 followed by addition of the novel secondary amine N-methyl
      (S)-dolaphenine 2 (prepared in 6 steps and 24% overall yield from N-Cbz-L
      phenylalanine) to give the beta-keto amide 16 which was converted directly to the
      required (E)-enol ether.

PMID- 12240227
TI  - Mesopore immobilised copper bis(oxazoline) complexes for enantioselective
      catalysis.
AB  - New supported heterogeneous catalysts have been synthesised through the tethering
      of copper bis(oxazoline) complexes to the surfaces of MCM-41 and MCM-48
      mesoporous materials, and the prepared catalysts shown to be highly active in the
      enantioselective cyclopropanation of styrene with ethyl diazoacetate.

PMID- 12240228
TI  - A facile, stereoselective [2 + 2] photoreaction mediated by curcurbit[8]uril.
AB  - The [2 + 2] photoreaction of (E)-diaminostilbene dihydrochloride proceeds with
      large rate acceleration and high stereoselectivity via formation of a stable 1:2
      host-guest complex with curcurbit[8]uril in solution.

PMID- 12240229
TI  - Synthesis and characterization of poly(2,3,5,6-tetrafluoro-1,4
      phenylenevinylene).
AB  - Poly(2,3,5,6-tetrafluoro-1,4-phenylenevinylene) (PTFPV) was prepared for the
      first time by the Stille cross-coupling reaction and the resulting material was
      characterized through MALDI-TOF mass spectrometry, employing a novel sample
      preparation protocol suitable for insoluble compounds; preliminary optical and
      electrooptical measurements were performed.

PMID- 12240230
TI  - Preparation of highly photocatalytic active nano-sized TiO2 particles via
      ultrasonic irradiation.
AB  - A novel method for preparing highly photoactive nano-sized TiO2 photocatalysts
      with anatase and brookite phases has been developed by hydrolysis of titanium
      tetraisoproproxide in pure water or a 1:1 EtOH-H2O solution under ultrasonic
      irradiation; the photocatalytic activity of TiO2 particles prepared by this
      method exceeded that of Degussa P25.

PMID- 12240231
TI  - Highly efficient oligosaccharide synthesis on water-soluble polymeric primers by
      recombinant glycosyltransferases immobilised on solid supports.
AB  - Recombinant beta-1,4-galactosyltranferase (beta 1,4-GalT) and alpha-2,6
      sialytransferase (alpha 2,6-SiaT) immobilised covalently with activated Sepharose
      beads were employed for the practical synthesis of a trisaccharide derivative,
      Neu-5Ac alpha(2-->6)Gal beta(1-->4)GlcNAc beta-O-(CH2)6-NH2, on a water-soluble
      primer having GlcNAc residues through a alpha-chymotrypsin-sensitive linker.

PMID- 12240232
TI  - First crystallographic signature of amyloid-like fibril forming beta-sheet
      assemblage from a tripeptide with non-coded amino acids.
AB  - The model tripeptide Boc-beta-Ala(1)-Aib(2)-beta-Ala(3)-OMe 1 [beta-Ala: beta
      alanine, Aib: alpha-aminoisobutyric acid] forms an infinite parallel beta-sheet
      structure through intermolecular interactions in single crystals and from the SEM
      diagram of this peptide, it is evident that the compound has fibrillar
      morphology, a characteristic of neurodegenerative disease causing amyloid
      aggregate.

PMID- 12240233
TI  - 8,16,24,32,40,48-Hexamethoxy[2.6]metacyclophane-1,9,17,25,33,41-hexayne: a novel
      near-planar ammonium-selective ionophore.
AB  - The titled cyclophane (cyclic [6]metaphenylacetylene) with six methoxy groups
      inside the cavity has a nearly planar carbon framework, forms open-channel
      structures in the crystal, and exhibits an ammonium-selective ionophoric property
      in spite of the considerably large cavity.

PMID- 12240234
TI  - A new tricyclic ring and a nitrogen-sulfur analogue of the tri-pentagon bowl.
      Substituted 5,6,7,7a-tetrahydropyrrolo[2,1-b]-1,3,4-thiadiazole- endo-6,7
      dicarboxyimides.
AB  - The first examples of a bowl-shaped tricyclic nitrogen-sulfur analogue of the tri
      pentagon bowl are reported; substituted 5,6,7,7a-tetrahydropyrrolo[2,1-b]-1,3,4
      thiadiazole-endo-6,7-dicarboxyimides are synthesised by a relatively simple
      route.

PMID- 12240235
TI  - Production of ultra highly pure H2 and higher hydrocarbons from methane in one
      step at mild temperatures and development of the catalyst under non-equilibrium
      reaction conditions.
AB  - Ultra highly pure hydrogen and more valuable hydrocarbons are produced directly
      from methane in one step beyond the thermodynamic equilibrium conversion by
      integration of the dehydrogenation reaction and hydrogen separation with a Pd-Ag
      based membrane reactor at mild temperatures, and a highly active catalyst is
      developed under the non-equilibrium reaction conditions.

PMID- 12240236
TI  - The first redox controlled hydrogen bonded three-pole switch.
AB  - The first example of a redox controlled hydrogen bonded three-pole switch is
      described, which exploits both electrochemical oxidation and reduction of the
      host-guest dyad to modulate the intermolecular recognition properties.

PMID- 12240237
TI  - The first observation of the [Cp3Mn]- anion; structures of hexagonal [(eta 2
      Cp)3MnK.1.5thf] and ion-separated [(eta 2-Cp)3Mn]2[Mg(thf)6].2thf.
AB  - Hexagonal [(eta 2-Cp)3MnK.1.5thf] 1 and ion-separated [(eta 2
      Cp)3Mn]2[Mg(thf)6].2thf 2 are obtained from reactions of CpK and Cp2Mg,
      respectively, with manganocene, Cp2Mn; they are the first complexes to be
      structurally characterised containing the [Cp3Mn]- anion.

PMID- 12240238
TI  - Self-assisted tandem Michael-aldol reactions of alpha,beta-unsaturated ketones
      with aldehydes.
AB  - The tandem Michael-aldol reaction of 1-[2-(methylsulfanyl)-phenyl]prop-2-en-1-one
      (1) or the seleno congener 4 with p-nitrobenzaldehyde in the presence of BF3.Et2O
      gave the Baylis-Hillman adduct 2 or 5 and onium salt 3 or 6, respectively, and
      selenochromanone 7 from 4.

PMID- 12240239
TI  - Peptide conjugation: unexpected ring opening of azacrown ether nucleophiles in
      the oxazolone-based coupling.
AB  - Unexpected cleavage of the macrocylic ring of secondary azacrown ethers when
      interacting with the Aib8 (Aib = alpha-aminoisobutyric acid) oxazolone indicates
      the possibility for a new mechanism of peptide racemization due to
      transformations of the oxazolones formed from the N-derivatives of alpha-amino
      acids in peptide synthesis.

PMID- 12240240
TI  - Chemical modification of schizophyllan by introduction of a cationic charge into
      the side chain which enhances the thermal stability of schizophyllan-poly(C)
      complexes.
AB  - Combining oxidation with periodate and reductive amination, the amino group is
      introduced only in the side chain of schizophyllan and the product can bind to
      poly(C) with a higher dissociation temperature than that of the unmodified
      schizophyllan and poly(C) complex.

PMID- 12240241
TI  - Functionalized polyolefin synthesis using [P,O]Ni catalysts.
AB  - Nickel olefin polymerisation catalysts containing bulky phosphino-enolate ligands
      are shown to give methyl methacrylate end-functionalized polyolefins.

PMID- 12240242
TI  - Palladium-catalysed cross-coupling reactions in supercritical carbon dioxide.
AB  - Heck and Suzuki reactions proceed in good yield in supercritical carbon dioxide
      in the presence of palladium acetate and tri-tert-butylphosphine with both free
      and polymer-tethered substrates.

PMID- 12240243
TI  - A novel route to substituted 4-methylene-4,5-dihydroisoxazoles mediated by
      hafnium(IV) chloride.
AB  - Heating alkyl vinyl ketones and N-tert-butylarylmethylideneamine N-oxides in the
      presence of HfCl4 results in the formation of 4-methylene-4,5-dihydroisoxazoles
      in good yield.

PMID- 12240244
TI  - Hollow spheres of MCM-41 aluminosilicate with pinholes.
AB  - Hollow spheres of MCM-41 mesoporous aluminosilicates, with two small holes on the
      shell, have been synthesized from a surfactant-aluminosilicate gel composite.

PMID- 12240245
TI  - Banana-shaped mesogens: observation of a direct transition from the
      antiferroelectric B2 to nematic phase.
AB  - The synthesis and characterisation of the first banana-shaped mesogens which
      exhibit a direct transition from the antiferroelectric B2 phase to the nematic
      phase are reported.

PMID- 12240246
TI  - Asymmetric synthesis of 2-azido-1-arylethanols from azido aryl ketone-beta
      cyclodextrin complexes and sodium borohydride in water.
AB  - beta-Cyclodextrin catalyses for the first time the asymmetric reduction of alpha
      azido aryl ketones to corresponding alcohols of great significance using sodium
      borohydride in water. The azido group appeared to be the best fit among various
      groups studied. This asymmetric reduction using water as solvent overcomes many
      of the drawbacks in the existing methodologies.

PMID- 12240247
TI  - Acenaphthenic hopanoids, a novel series of aromatised triterpenoids occurring in
      crude oil.
AB  - A series of diaromatic 8,14-secohophanoids of microbial origin has been
      characterized in a petroleum by NMR studies, disclosing novel geochemical
      transformations.

PMID- 12240248
TI  - Adsorption and separation of amino acids from aqueous solutions on zeolites.
AB  - The adsorption of various amino acids on zeolites with different structures was
      studied with regard to dependence of the pH value of the solution and the
      aluminum content of the zeolite in order to design tailor-made adsorbents for
      amino acid separations.

PMID- 12240249
TI  - Enantioselective crystallization of D,L-amino acids induced by spontaneous
      asymmetric resolution of D,L-asparagine.
AB  - Racemic D,L-asparagine induced spontaneous asymmetric resolution of co-existing
      D,L-phenylalanine or D,L-tryptophan by recrystallization from a homogeneous
      aqueous solution, and the enantiomeric excess of phenylalanine or tryptophan in
      the resulting crystals correlated linearly with that of asparagine crystallized
      with phenylalanine or tryptophan.

PMID- 12240250
TI  - Sub-ppt detection limits for copper ions with Gly-Gly-His modified electrodes.
AB  - An electrochemical metal ion sensor has been developed with a detection limit of
      less than 0.2 ppt by the covalent attachment of the tripeptide Gly-Gly-His as a
      recognition element to a 3-mercaptopropionic acid modified gold electrode.

PMID- 12240251
TI  - Ab initio structure determination of BiPb2VO6 from powder diffraction data.
AB  - The crystal structure of BiPb2VO6 has been determined from powder diffraction
      data using a combination of direct methods and the novel approach of applying
      simulated annealing methods simultaneously to X-ray and neutron data; BiPb2VO6 is
      a polar, noncentrosymmetric, second harmonic generation active material and its
      crystal structure is one of the more complex to be solved ab initio from powder
      diffraction data.

PMID- 12240252
TI  - First synthesis of a highly symmetrical decakis-adduct of fullerene dimer C120.
AB  - The highly symmetrical decakis-cyclopropanated derivative of C120 was synthesized
      using template activation and the structure was determined by X-ray
      crystallography; the decakis-adduct was converted into the eicosa-carboxylic acid
      derivative that is water soluble.

PMID- 12240253
TI  - Synthesis and characterisation of (C4N2H12)(UO2)2(PO3H)2(PO2(OH)H)2: a three
      dimensionally connected actinide framework.
AB  - The material (C4N2H12)(UO2)2(PO3H)2(PO2(OH)H)2 (MUPH-1) has been prepared
      hydrothermally; it is a three dimensional structure consisting of four
      intersecting elliptical shaped one-dimensional channels, the largest channel has
      dimensions of 13.1 x 7.2 A.

PMID- 12240254
TI  - Direct in situ observation of increasing structural dimensionality during the
      hydrothermal formation of open-framework zinc phosphates.
AB  - The first time-resolved in situ X-ray diffraction studies of the hydrothermal
      crystallisation of open-framework zinc phosphates reveal a pathway of sequential
      crystallisation involving formation of a metastable low dimensional chain phase
      before the growth of three-dimensional zeolitic architectures.

PMID- 12240255
TI  - 3'-amino-2',4'-BNA: novel bridged nucleic acids having an N3'-->P5'
      phosphoramidate linkage.
AB  - Novel oligonucleotide analogues, containing a 3'-amino-2',4'-BNA unit, were
      successfully synthesized, and they showed superior duplex and triplex forming
      ability as well as BNA itself, along with remarkable enzymatic stability.

PMID- 12240256
TI  - Directed assembly of multilayers--the case of Prussian blue.
AB  - We introduce the concept of 'directed assembly' of multilayers on surfaces: the
      overall process involves the exposure of a surface to a series of solutions
      containing, alternately, adsorbable cations and adsorbable anions, and these are
      gradually built up into well-defined multilayer structures.

PMID- 12240257
TI  - Reactivity of a metallacyclopentatriene intermediate: metal-to-ligand-to-metal re
      migration of a phosphine ligand versus a 1,2 hydrogen shift.
AB  - The reaction of nona-2,7-diyne, deca-2,8-diyne and hex-1-yne with
      [RuCp(PR3)(MeCN)2]PF6 (R = Cy, Ph, Me) affords, depending on the structure of the
      alkyne and the substituent of the phosphine ligand, ruthenium
      metallacyclopentatriene, allyl carbene and/or butadienyl carbene complexes
      involving either metal-to-ligand-to-metal migration of the phosphine ligand with
      concomitant C-H activation or a facile 1,2 hydrogen shift.

PMID- 12240258
TI  - Dioxygen activation by a neutral beta-diketiminato copper(I) ethylene complex.
AB  - The synthesis and structure of two thermally stable neutral beta-diketiminato
      copper(I) olefin complexes are presented along with the structure of a Cu(II)2(mu
      OH)2 dimer that results from the reaction of the Cu(I) ethylene complex with O2
      via the proposed intermediacy of a Cu(III)2(mu-O)2 species.

PMID- 12240259
TI  - Gold nanoparticles containing redox-active supramolecular dendrons that recognize
      H2PO4-.
AB  - Gold nanoparticles have been functionalized with thiol dendrons containing three
      redox active amidoferrocenyl or silylferrocenyl units; using cyclic voltammetry,
      these dendronized gold nanoparticles recognize H2PO4-.

PMID- 12240260
TI  - Immobilization of chlorophyll derivatives into mesoporous silica and energy
      transfer between the chromophores in mesopores.
AB  - Chlorophyll derivatives possessing triethoxysilyl groups have been synthesized
      for the first time and grafted on mesoporous silica to construct an efficient
      energy transfer system between the chromophores.

PMID- 12240261
TI  - One-way EZ-isomerization of bis(n-butylammonium) (Z,Z)-muconate under
      photoirradiation in the crystalline state.
AB  - One-way EZ-isomerization of bis(n-butylammonium) (Z,Z)-muconate [(Z,Z)-hexa-2,4
      diene-1,6-dioate] to the corresponding (E,E)-isomer quantitatively proceeded in
      the crystalline state under photoirradiation with a high-pressure mercury lamp,
      being a new type of crystal-to-crystal reaction.

PMID- 12240262
TI  - A novel cage organotellurate(IV) macrocyclic host encapsulating a bromide anion
      guest: [Li(THF)4][(PriTe)12O16Br4(Li(THF)Br)4)Br].2THF.
AB  - The first structural report of an unprecedented organotellurate(IV) inorganic
      organic hybrid macrocyclic host encapsulating a bromide anion guest is described.

PMID- 12240263
TI  - Formation of stable alkenyl carbenium ions in high yield by adsorption of 1
      methylcyclopentene on zeolite Y at low temperature.
AB  - The formation of dimerized alkenyl carbenium ions, characterized by an IR band at
      1513 cm-1 and a UV band at 323 nm, was observed by adsorption of 1
      methylcyclopentene on HY and DY zeolites at temperatures as low as 150 K.

PMID- 12240264
TI  - Preparation of novel, moisture-stable, Lewis-acidic ionic liquids containing
      quaternary ammonium salts with functional side chains.
AB  - A range of novel, moisture-stable, Lewis-acidic ionic liquids has been prepared
      by mixing appropriate molar ratios of MCl2 (M = Zn and/or Sn) and quaternary
      ammonium salts of formula [Me3NC2H4Y]Cl (Y = OH, Cl, OC(O)Me, OC(O)Ph); the
      influence of substituent Y and metal M on the physical properties of the melts
      has been investigated.

PMID- 12240265
TI  - Supramolecular assemblies formed by new L-lysine derivatives of viologens.
AB  - L-Lysine derivatives of viologens form supramolecular assemblies of fibers and
      ribbons in some aromatic solvents, and the charge separation reaction in these
      self-assembling systems proceeds with a similar efficiency to the MV2+ system.

PMID- 12240266
TI  - First synthesis of porphyrin-phthalocyanine heterodimers with a direct ethynyl
      linkage.
AB  - The first synthesis of two porphyrin-phthalocyanine heterodimers with a direct
      triple bond linkage between the macrocycles, designed for the study of photo
      induced energy and electron transfer processes, is presented along with
      preliminary ground state and fluorescence spectroscopic data.

PMID- 12240267
TI  - Novel organoaluminium (and gallium) carboxylate-bridged ring systems.
AB  - Treatment of the Schiff-base ligand [3,5-But2-2-(OH)C6H2CHNC6H4-2-(CO2H)] with
      either Me3Al, Me2AlCl or Me3Ga affords 16-membered macrocyclic tetramers
      containing both four- and six-coordinate metal centres.

PMID- 12240268
TI  - The first fluorescent sensor for boronic and boric acids with sensitivity at sub
      micromolar concentrations--a cautionary tale.
AB  - The first reported fluorescent sensor for boronic and boric acids is actually not
      a sensor for boronic and boric acids but rather is a sensor for protons; the
      system is also not the first fluorescent sensor since Alizarin has been used as a
      fluorescent sensor for boric acids since 1936.

PMID- 12240269
TI  - Non-covalent interactions exert extraordinary influence over conformation and
      properties of a well-known supramolecular building block.
AB  - At low pH, and in the presence of 4,4'-bipyridine, p-sulfonatocalix[4]arene
      crystallizes in the 1,3-alternate conformation rather than the expected cone
      conformation and exhibits remarkable stability.

PMID- 12240270
TI  - A new highly fluorescent probe for monosaccharides based on a donor-acceptor
      diphenyloxazole.
AB  - A diphenyloxazole substituted with a dimethylamino and a boronic acid group
      showing intramolecular charge transfer in the excited state undergoes large
      spectral changes in the presence of monosaccharides.

PMID- 12240272
TI  - Aminosubstituted tert-butylsulfinylferrocenes as a new family of chiral ligands:
      asymmetric addition of diethylzinc to aldehydes.
AB  - A ready access to a new family of planar chiral ferrocenes, the (RFc,RS)-2-amino
      substituted 1-tert-butylsulfinylferrocenes, is described; in the case of the
      sulfonamide series enantioselectivities of up to 96% were obtained in the
      addition of Et2Zn to aromatic aldehydes.

PMID- 12240271
TI  - Efficient synthesis of the antigenic phosphoglycans of the Leishmania parasite.
AB  - Antigenic phosphoglycan repeats of the Leishmania parasite can be assembled in a
      flexible and efficient manner without involving any glycosidation steps, and the
      chain can be extended either towards the non-reducing (6'-OH) or reducing (1-OH)
      end suitable for synthesis of lipophosphoglycan, proteophosphoglycan and
      analogues.

PMID- 12240273
TI  - Interfacial synthesis of hollow microspheres of mesostructured silica.
AB  - Hollow microspheres with ordered mesoporous walls are synthesised under ambient
      conditions by a simple procedure involving dilution and neutralisation of an
      aqueous tetraethoxysilane/cetyltrimethylammonium bromide reaction mixture.

PMID- 12240274
TI  - An enantio- and stereocontrolled synthesis of (-)-mycestericin E via cinchona
      alkaloid-catalyzed asymmetric Baylis-Hillman reaction.
AB  - A new enantiocontrolled synthesis of a potent immunosuppressant(-)-mycestericin E
      has been accomplished by using cinchona alkaloid-catalyzed asymmetric Baylis
      Hillman reaction of an aldehyde with 1,1,1,3,3,3-hexafluoroisopropyl acrylate and
      Lewis acid-promoted cyclisation of an epoxytrichloroacetimidate as the key steps.

PMID- 12240275
TI  - Triblock copolymer assisted synthesis of periodic mesoporous organosilicas (PMOs)
      with large pores.
AB  - Periodic mesoporous organosilicas (PMOs) with unusually large pores and high BET
      surface areas have been synthesized using triblock PEO-PPO-PEO copolymer P123 as
      the structure-directing agent and 1,2-bis(trimethoxysilyl)ethane (BTME) as the
      organically bridged silica source.

PMID- 12240276
TI  - Understanding organic reactions in water: from hydrophobic encounters to
      surfactant aggregates.
AB  - A crucial factor in realising a green chemical process in solution involves the
      choice of a safe, non-toxic and cheap solvent. Water is the obvious choice.
      Despite solubility problems, considerable interest has developed recently in
      organic chemistry in water. This interest also results from the fact that
      association and chemical reactions often benefit noticeably from the special
      properties of water, resulting mainly from its small molecular size, its three
      dimensional hydrogen-bond network and hydrophobic interactions which are so
      unique for liquid water. Here we discuss organic reactions and assembly processes
      in water, largely taken from experiments performed in the authors' laboratories.
      We show that non-covalent interactions in water can be utilised for fine tuning
      organic reactions in aqueous media.

PMID- 12240278
TI  - Palladium catalysed 3-component cascade synthesis of bis(2-arylallyl) tertiary
      amines from aryl iodides, allene and primary amines.
AB  - A 3-component cascade synthesis of bis(2-arylallyl) tertiary amines from aryl
      iodide, allene and primary aliphatic amines is described; chiral amines give
      analogous products with no detectable racemisation; mixtures of two different
      aryl iodides can be utilised to give the mixed tertiary amines as the sole, or
      major, product; the reaction is sensitive to stereoelectronic effects which lead
      to mono(2-arylallyl) secondary amines.

PMID- 12240277
TI  - Difluoromethylene analogues of aspartyl phosphate: the first synthetic inhibitors
      of aspartate semi-aldehyde dehydrogenase.
AB  - The difluoromethylene analogue of aspartyl phosphate 6 has been prepared by the
      fluoride catalysed coupling of diethyl trimethylsilyldifluoromethyl phosphonate
      with an appropriate aldehyde followed by Dess-Martin oxidation and deprotection;
      the deprotected compound inhibited (KI 95 microM) aspartate semi-aldehyde
      dehydrogenase, a key enzyme involved in bacterial amino acid and peptidoglycan
      biosynthesis.

PMID- 12240279
TI  - A dramatic improvement of epoxide selectivity of [Ti,Al]-beta by ion-exchange
      with quaternary ammonium salts.
AB  - Ion-exchange of [Ti,Al]-beta with quaternary ammonium acetates greatly enhances
      the epoxide selectivity in the oxidation of alkenes with hydrogen peroxide; this
      is due to the selective poisoning of the acid sites without suppressing the
      oxidation activity of Ti sites.

PMID- 12240280
TI  - Catalyst-free reactions under solvent-free conditions: microwave-assisted
      synthesis of heterocyclic hydrazones below the melting points of neat reactants.
AB  - The reaction of neat 5- or 8-oxobenzopyran-2(1H)-ones, 1-3, with a variety of
      aromatic and heteroaromatic hydrazines, 4, is remarkably accelerated upon
      irradiation in a household microwave oven in the absence of any catalyst, solid
      support or solvent thus providing an environmentally friendly route to several
      heterocyclic hydrazones.

PMID- 12240281
TI  - Iron polynitroporphyrins bearing up to eight beta-nitro groups as interesting new
      catalysts for H2O2-dependent hydrocarbon oxidation: unusual regioselectivity in
      hydroxylation of alkoxybenzenes.
AB  - A series of iron porphyrins bearing one to eight beta-nitro substituents were
      synthesized and evalauted as catalysts for hydrocarbon oxidation with H2O2; iron
      porphyrins bearing five or six beta-nitro groups were the best catalysts for
      cyclooctene epoxidation and adamantane or anisole hydroxylation without need of a
      cocatalyst, and led to very different regioselectivities with either H2O2 or PhIO
      as oxidants, as shown by an unusual ortho-hydroxylation of alkoxybenzenes highly
      favored in the H2O2-dependent oxidations.

PMID- 12240282
TI  - ITQ-16, a new zeolite family of the beta group with different proportions of
      polymorphs A, B and C.
AB  - ITQ-16 is a new zeolite family formed by polymorphs A, B and C of the beta
      intergrowth in which the proportion of polymorph C can be controlled by changing
      the organic structure directing agent and/or by changing the Ge content of the
      synthesis gel; ITQ-16 can be synthesised either in fluoride or fluoride-free
      medium and Al can be introduced in the framework giving a material with very
      strong Bronsted acidity.

PMID- 12240283
TI  - Enantioselective deprotonation reactions using polymer-supported chiral magnesium
      amide bases.
AB  - Novel and readily accessible polymer-supported chiral magnesium amide reagents
      have been prepared and shown to be effective in the asymmetric deprotonation of a
      series of prochiral cyclohexanones, affording good to excellent levels of both
      conversion and enantiomeric ratio (up to 93:7); the Merrifield-based chiral amine
      species has been shown to be readily recyclable.

PMID- 12240284
TI  - Generation of chromioenamines by reduction of O-acetyloximes with chromium(II)
      and their application.
AB  - Chromioenamines can be generated by treatment of O-acetyloximes with chromium(II)
      via two steps of one-electron reduction and successive isomerization, and the
      species react with aldehydes to give gamma-amino alcohols after reduction with
      LiAlH4.

PMID- 12240285
TI  - Synthesis and application of novel catalytically active polymers containing 1,4,7
      triazacyclononanes.
AB  - New polymers containing 1,4,7-triazacyclononanes have been synthesised by means
      of ring opening metathesis polymerisation (ROMP); their complexes with Mn(II)
      catalyse the oxidation of simple olefins by hydrogen peroxide.

PMID- 12240286
TI  - Novel synthesis of cyclobutanone derivatives via dimetalation of iminium ions
      with the TiCl4-trialkylamine reagent system.
AB  - Iminium salts are generated in situ, react with TiCl4-trialkylamines, and diaryl
      ketones to produce 3,3-diaryl-cyclobutanones in moderate to good yields.

PMID- 12240287
TI  - The first 1,3-digermyla-2-nickela-carboranylene and the Ni-catalyzed double
      germylation of unsaturated organic substrates.
AB  - The reaction of o-bis(dimethylgermyl)carborane with Ni(PEt3)4 in pentane affords
      the reactive intermediate, [o-(GeMe2)2C2B10H10]Ni(PEt3)2 2: the facile double
      germylation of unsaturated organic substrates catalyzed by 2 is reported.

PMID- 12240288
TI  - Direct NO group transfer from S-nitrosothiols to iron centres.
AB  - A number of S-nitrosothiols react rapidly with the Fe(II) complexes of 2,3
      dimercapto-1-propanesulfonic acid (DMPS) and of N-methyl-D-glucamine
      dithiocarbamate (MGD), transferring the NO group directly to the iron centres.

PMID- 12240289
TI  - Control over directional metal-metal charge transfer in cyanide-bridged
      dimanganese complexes: effects of mu-CN linkage isomerism and ancillary ligand
      set.
AB  - Synthesis and characterisation of cyano-bridged complexes of the form [(eta
      C5R4Me)L(ON)Mn(mu-XY)Mn(CO)2-L'(dppm)]z (X,Y = C,N; z = 1-3) shows that
      systematic variation of the orientation of the CN bridge and the nature and
      geometric arrangement of the ancillary ligands affords control of the direction
      and energy of metal-metal charge transfer in the mixed valence dications.

PMID- 12240290
TI  - The first example of catalytic N-oxidation of tertiary amines by tungstate
      exchanged Mg-Al layered double hydroxide in water: a green protocol.
AB  - A green process, using a recyclable tungstate-exchanged Mg-Al layered double
      hydroxide (LDH-WO4(2-)) heterogenised catalyst and aqueous H2O2 oxidant in water,
      leads to N-oxidation of aliphatic tert-amines to amine N-oxides in quantitative
      yields, at a high rate at room temperature.

PMID- 12240291
TI  - Nanoparticle routes to mesoporous titania thin films.
AB  - Controlled aging of TiO2 nanoparticles blended with diblock copolymers and
      processed into dip-coated thin films led to ordered mesostructures with cubic and
      hexagonal symmetries that can be transformed into mesoporous TiO2 by calcination.

PMID- 12240292
TI  - Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole.
AB  - Aggregation greatly boosts emission efficiency of the silole, turning it from a
      weak luminophor into a strong emitter.

PMID- 12240293
TI  - One-step synthesis and redox properties of dodecahydro-3a,9a-diazaperylene--the
      most easily oxidized p-phenylenediamine.
AB  - Dodecahydro-3a,9a-diazaperylene (DHDAP) was prepared in one step from p
      phenylenediamine and 1-bromo-3-chloropropane, and its first redox potential is
      292 mV more negative than the first redox potential of N,N,N',N'-tetramethyl-p
      phenylenediamine (TMPD), thus becoming the most easily oxidized p
      phenylenediamine homologue.

PMID- 12240294
TI  - Enhancement of a two-photon absorption cross section (TPACS)--design and
      synthesis of a novel class of photochromic molecules with large TPACS.
AB  - Two novel photochromic compounds were designed and synthesized; the two-photon
      absorption (TPA) cross section of both were measured with a nanosecond laser
      pulse; their TPACS (delta) values are around 25 x 10(-46) cm4 s photon-1 molecule
      1 in acetonitrile; the molecular structure of the target compounds have a 3
      methyl-1-benzothiophen-2-yl moiety, which can greatly enhance the two-photon
      absorption cross section.

PMID- 12240295
TI  - Zeolite membrane on catalyst particles for selective formation of p-xylene in the
      disproportionation of toluene.
AB  - The selective formation of p-xylene is shown in toluene disproportionation using
      a new catalyst which is surrounded with a permselective membrane.

PMID- 12240296
TI  - Ab initio study of oxygen atom transfer from hydrogen peroxide to trimethylamine.
AB  - Unlike what has been theoretically proposed for ammonia oxidation with hydrogen
      peroxide, trimethylamine oxidation occurs with a concerted mechanism, which is
      favored even when an explicit water molecule is added or continuum solvent
      (water) is simulated.

PMID- 12240297
TI  - A new phenomenon in the induction period of the methane dehydroaromatization
      reaction.
AB  - The induction period of dehydroaromatization of methane to benzene over Mo/HZSM-5
      had been investigated in real-time by the resonant-enhanced two-photon ionization
      (RE2PI) technique; it is remarkable that there is a small amount of benzene
      formed in the early stage of the induction period; we suggest that the trace
      amount of benzene was caused by the reduction of the original Mo6+ ion during the
      induction period and the Mo6+ species has a slight catalytic activity for methane
      benzene conversion.

PMID- 12240298
TI  - Characterisation of a hydroxymandelate oxidase involved in the biosynthesis of
      two unusual amino acids occurring in the vancomycin group of antibiotics.
AB  - ORF22 from the chloroeremomycin gene cluster has been cloned, expressed and
      characterised as a hydroxymandelate oxidase (HmO) that is involved in the
      formation of both (S)-4-hydroxyphenylglycine and (S)-3,5-dihydroxyphenylglycine.

PMID- 12240299
TI  - Methanol to hydrocarbons: enhanced aromatic formation using a composite Ga2O3-H
      ZSM-5 catalyst.
AB  - Addition of beta-Ga2O3 to H-ZSM-5, as a physical mixture, enhances the formation
      of aromatic hydrocarbons in the methanol to hydrocarbons reaction.

PMID- 12240300
TI  - Monocarbaborane chemistry. Preparation and characterisation of [4-CB8H9]-, the
      'missing' closo-carbaborane anion.
AB  - Thermolysis in the solid state of Cs+[arachno-CB9H14]-, or of Cs+[nido-CB9H12]-,
      or the oxidation of nido-1-CB8H12 with I2 in THF at -78 degrees C in the presence
      of NEt3, gives the first nine-vertex closo monocarbaborane, the stable [closo-4
      CB8H9]- anion, in yields of 56, 61 and 75%, respectively.

PMID- 12240301
TI  - Addition of diprotic nucleophiles to a C60-tetrazine monoadduct: structural
      reassignment and correction of a novel rearrangement.
AB  - C60-tetrazine Diels-Alder adducts bearing electron deficient dihydropyridazine
      groups undergo chemoselective amination and hydration reactions upon addition of
      primary aliphatic amines and water, respectively, to form new adducts with 4,5
      dihydropyrazole groups nested atop the [60]fullerene skeleton.

PMID- 12240302
TI  - Identification of Tyr58 as the proton donor in the aspartate-alpha-decarboxylase
      reaction.
AB  - The decarboxylation of L-aspartate by E. coli L-aspartate-alpha-decarboxylase
      (ADC) is shown to occur with retention of configuration; analysis of the protein
      structure identifies Tyr58 as the proton donor in the decarboxylation mechanism.

PMID- 12240303
TI  - Novel silver(I)-organic coordination polymers: conversion of extended structures
      in the solid state as driven by argentophilic interactions.
AB  - Structurally distinct coordination polymers [Ag(bpp)]ClO4 1 and [Ag(bpp)]PF6 2
      [bpp = 1,3-bis(4-pyridyl)propane] have been assembled; the conversion of 1 into 2
      on treatment with NaPF6 is driven by argentophilic interactions and is the first
      such transformation reported for silver(I)-organic coordination polymers.

PMID- 12240305
TI  - A space group assignment of ZrP2O7 obtained by 31P solid state NMR.
AB  - 2-D 31P dipolar recoupling magic angle spinning NMR has been used to determine
      the true symmetry of the low temperature structure of ZrP2O7 for the first time.

PMID- 12240304
TI  - Crystal engineering of microporous 'Chinese-lantern' compounds to improve their
      ability to reversibly adsorb sulfur dioxide.
AB  - Three new 'Chinese lantern' complexes [XMn(mu-dppO2)4MnX](2+)2X-.4MeOH.Me2CO [X =
      Cl, Br, I; dppO2 = 1,3-bis(diphenylphosphinoyl)propane], have been structurally
      characterised using single-crystal X-ray diffraction and shown to have increasing
      affinity for SO2 across the series Cl < Br < I via thermogravimetric
      measurements.

PMID- 12240306
TI  - First observation of clusters for solvated tropylium ions.
AB  - We have first observed clusters for solvated tropylium ions (Tr+(ROH)n) which
      were isolated from ROH-CH3CN (1:1 by vol.; R = Me, Et, and Prn) solutions by
      using a specially designed mass spectrometer and found the clear-cut essential
      features concerning the solvation structure around Tr+.

PMID- 12240307
TI  - Enhanced activity and stability of a Cu/SiO2 catalyst for the reverse water gas
      shift reaction by an iron promoter.
AB  - An Fe promoter inhibits the sintering of Cu particles and oxidation of the Cu
      surface, resulting in high catalyst activity and stability.

PMID- 12240308
TI  - Penetration of pyrene and its derivatives into polystyrene latex particles as
      studied by fluorescence spectroscopy.
AB  - Small hydrophobic pores (channels) in polystyrene latex particles were found by
      investigating the penetration of pyrene using fluorescence techniques.

PMID- 12240309
TI  - 1,2,4,3,5-benzotrithiadiazepine and its unexpected hydrolysis to unusual 7H,14H
      dibenzo[d,i][1,2,6,7,3,8]tetrathiadiazecine.
AB  - Previously unknown 1,2,4,3,5-benzotrithiadiazepine 1 was prepared by 1:1
      condensation of Ph-N=S=N-SiMe3 with S2Cl2 followed by intramolecular ortho
      cyclization of [Ph-N=S=N-S-S-Cl] intermediate, and hydrolyzed in pyridine to
      unusual macrocyclic 7H,14H-dibenzo[d,i][1,2,6,7,3,8]tetrathiadiazecine 2.

PMID- 12240310
TI  - New high-nuclearity Ni-Pt carbonyl clusters: synthesis and X-ray structure of the
      ordered [Ni24Pt14(CO)44]4- and the substitutionally Ni/Pt disordered [Ni10(Ni6
      xPtx)Pt8(CO)30]4- (x = 1.92) tetraanions.
AB  - The reaction of [NnBu4]2[Ni6(CO)12] in THF solution with 1.5-2 equivalents of
      K2PtCl4 leads to formation of the [Ni24Pt14(CO)44]4- and [Ni10(Ni6
      xPtx)Pt8(CO)30]4- (x approximately 2) tetraanions, the latter presents a
      localised substitutional Ni/Pt disorder and an unprecedented close-packed metal
      structure.

PMID- 12240311
TI  - Poly(distyrylbenzene-block-sexi(ethylene oxide)), a highly luminescent
      processable derivative of PPV.
AB  - A block copolymer of distyrylbenzene with sexi(ethylene oxide) spacers displays
      high solid state photoluminescence efficiency (34%). Single layer light-emitting
      diodes with calcium or aluminium cathodes exhibit luminances over 2000 cd m-2 and
      efficiencies of 0.5 cd A-1.

PMID- 12240312
TI  - Synthesis and structural characterization of a silver complex of a mixed-donor N
      heterocyclic carbene linked cyclophane.
AB  - The synthesis of a dicationic imidazolium-linked cyclophane and a dimeric silver
      N-heterocyclic carbene complex, that is the first silver complex with a N
      heterocyclic carbene ligand involved in a pi-bonding interaction, is reported.

PMID- 12240313
TI  - Production of Au-Ag alloy nanoparticles by laser ablation of bulk alloys.
AB  - Gold-silver alloy nanoparticles can be produced by pulsed laser irradiation of
      bulk alloy metals in water, preserving the stoichiometry of the target metals.

PMID- 12240314
TI  - Asymmetric synthesis of 2-substituted piperidines using a multi-component
      coupling reaction: rapid assembly of (S)-coniine from (S)-1-(1-phenylethyl)-2
      methyleneaziridine.
AB  - (S)-Coniine is made using a reaction which assembles the piperidine ring by the
      sequential formation of four new chemical bonds and installs the C-2 stereogenic
      centre with high levels of diastereocontrol (90% de).

PMID- 12240315
TI  - Triple linking of the decaboranyl cluster. Structure of [(SMe2)2B10H10(B10H13)2]
      as determined by synchrotron X-ray diffraction analysis.
AB  - In an attempt to find generic routes to multiple inter-cluster sigma-linking,
      mild thermolysis of [6,9-(SMe2)2-arachno-B10H12] 1 in inert hydrocarbon solution
      gives the tridecaboranyl species [6,9-(SMe2)2-arachno-B10H(10)-1,5-(6'-nido
      B10H13)2] 3 (23%).

PMID- 12240316
TI  - Monocarbaborane anion chemistry. The elusive C-arylated [PhCB11H11]-, [PhCB9H9]-
      and [PhCB8H8]- anions.
AB  - B10H14 and PhCHO yield [6-Ph-nido-6-CB9H11]- (94%), from which the nine-vertex C
      phenyl monocarbaborane anion [4-Ph-closo-4-CB8H8]- (68%) can be obtained by
      heating at 200 degrees C, and from which the twelve- and ten-vertex analogues [1
      Ph-closo-1-CB11H11]- (50%) and [4-Ph-closo-4-CB9H9]- (25%) can be obtained by
      heating at 210 degrees C with BH3(NEt3).

PMID- 12240317
TI  - New and easy route to primary cyclopropylamines from nitriles.
AB  - Starting from readily available substrates, we have developed a new synthesis of
      primary cyclopropylamines. The reaction involves a cooperative Ti(II)- and Lewis
      acid-mediated coupling of alkanenitriles with Grignard reagents.

PMID- 12240318
TI  - A remarkably stable hydrogen-bonded porphyrin.iron(terpyridine) ion pair.
AB  - Even in highly competitive solvents such as DMSO, strong bimolecular association
      and subsequent fluorescence quenching result from the combination of hydrogen
      bonding and ion pairing between a porphyrinic bis(carboxylate) dianion and an
      iron(terpyridine) bis(urea).

PMID- 12240319
TI  - Ring opening-cross metathesis of unstrained cycloalkenes.
AB  - Unstrained cycloalkenes undergo ruthenium-catalysed ring opening-cross metathesis
      reactions with simple alpha, beta-unsaturated carbonyl compounds under mild
      conditions.

PMID- 12240320
TI  - Barbier reaction in the regime of metal oxide: the first example of carbonyl
      allylation mediated by tetragonal tin(II) oxide.
AB  - Facile synthesis of homoallylic alcohols is achieved from allyl halides and
      aldehydes or ketones over an all-oxide heterogenous media involving beta-SnO and
      catalytic Cu2O.

PMID- 12240321
TI  - Enzymatic synthesis of pyruvic acid from acetaldehyde and carbon dioxide.
AB  - A new enzymatic synthesis of pyruvic acid from acetaldehyde and carbon dioxide
      has been developed.

PMID- 12240322
TI  - Synthesis of alkenylene-bridged macrocyclic silsesquioxanes by ruthenium or
      rhodium-catalyzed ring-closing reactions of bis(allyldimethylsilyl) groups.
AB  - Novel alkenylene-bridged oligosilsesquioxanes composed of half-caged structures
      with 16- or 17-membered rings as well as a titanium-containing molecule with a
      twisted 21-membered macrocycle have been synthesized by ruthenium or rhodium
      catalyzed ring-closing reactions of silsesquioxanes with bis(allyldimethylsilyl)
      groups.

PMID- 12240323
TI  - A family of highly active copper(I)-homoscorpionate catalysts for the alkyne
      cyclopropenation reaction.
AB  - Equimolar mixtures of ethyl diazoacetate and alkynes can be converted into
      cyclopropenes in very high yields, at room temperature, through the intermediacy
      of readily available Cu(I) catalysts containing trispyrazolylborate ligands.

PMID- 12240324
TI  - Additional of functional vinylzinc reagents to nitrones: synthesis of (E)-N
      allylhydroxylamines and their rearrangement into (E)-O-allylhydroxylamines.
AB  - The vinylzinc reagents derived from hydrozirconation of alkynes and
      transmetallation add readily to nitrones to yield pure (E)-N-allylhydroxylamines;
      some of these rearrange into O-allylhydroxylamines.

PMID- 12240325
TI  - An unprecedented recyclable catalyst system for asymmetric hydroboration.
AB  - Immobilised preformed chiral homogeneous catalysts were subjected to catalytic
      hydroboration of styrene with catecholborane and the activity, regio- and
      enantioselectivity observed were similar to those found when the corresponding
      homogeneous catalyst was used, remaining constant for several consecutive runs.

PMID- 12240326
TI  - Generation of methoxide from methane and oxygen under mild conditions over an
      Sm2O3 catalyst investigated by in situ IR spectroscopy.
AB  - The generation of methoxide over an Sm2O3 catalyst was clearly observed under a
      CH4-O2 atmosphere at 323 K by in situ Fourier transform IR spectroscopy.

PMID- 12240327
TI  - Direct evidence for a ruthenium(IV) oxo complex-mediated oxidation of a
      hydroxamic acid in the presence of phosphine oxide donors.
AB  - Ruthenium(II) complexes can be used to oxidise N-Boc hydroxylamine the the
      presence of tert-butylhydroperoxide to the corresponding nitroso dienophile,
      which is trapped using cyclohexa-1,3-diene as the hetero-Diels-Alder adduct;
      direct evidence has been obtained for the intervention of a triphenylphosphine
      oxide-stabilised ruthenium(IV) oxocomplex as the catalytically active species.

PMID- 12240328
TI  - Incorporation of a novel nucleobase allows stable oligonucleotide-directed triple
      helix formation at the target sequence containing a purine.pyrimidine
      interruption.
AB  - Thermal denaturation experiments have established that an oligonucleotide
      incorporating the artificial nucleobase S, does form a stable triplex with a
      double stranded DNA which exhibits a pyrimidine interruption within the
      oligopurine sequence.

PMID- 12240329
TI  - Novel chiral imidazole cyclophane receptors: synthesis and enantioselective
      recognition for amino acid derivatives.
AB  - Novel chiral imidazole cyclophane receptors were synthesized by highly selective
      N-alkylation of the imadazolyl 1N-position of the bridged histidine diester 2
      with the dibromide in the presence of NaH; these receptors exhibit good chiral
      recognition toward the enantiomers of L- and D-amino acid derivatives (up to
      KD/KL = 3.52, delta delta G0 = -3.11 kJ mol-1) in CHCl3 at 25.0 degrees C.

PMID- 12240330
TI  - Electron transfer reactions at gold nanoparticles.
AB  - It is demonstrated that scanning electrochemical microscopy can be used to
      investigate the kinetics of electron transfer reactions catalysed by metal
      nanoparticles supported on an insulating substrate.

PMID- 12240331
TI  - Synthesis and absolute configuration of lactone II isolated from Streptomyces sp.
      Go 40/10.
AB  - All four possible stereoisomers of lactone II isolated from Streptomyces sp. Go
      40/10, an autoregulator, have been efficiently synthesized in a stereoselective
      manner starting from (S)-malic acid and sorbic acid, and the absolute
      configuration was determined to be 2S, 3S, 9R, 10S.

PMID- 12240332
TI  - Redirect the assembly of hexagonal MCM-41 into cubic MCM-48 from sodium silicate
      without the use of an organic structure modifier.
AB  - In contrast to earlier methods requiring the presence of organic modifiers for
      the preparation of cubic MCM-48 mesostructures from low cost sodium silicate, we
      show that this three dimensional framework structure can be readily assembled in
      the absence of co-surfactants simply by using the overall SiO2/OH- ratio as means
      of controlling the surfactant packing parameter.

PMID- 12240333
TI  - A phenoxyl radical complex of copper(II).
AB  - A new N,O-bidentate pro-ligand (HL), [ML2] (M = Cu, Zn) and [CuL2][BF4] have been
      synthesised; [CuL2].4DMF and [CuL2][BF4].2CH2Cl2 have been crystallographically
      and spectroscopically characterised; these data indicate that [CuL2]+ cations are
      constituted as [Cu2+(L.)(L-)]+ and involve the phenoxyl radical L..

PMID- 12240334
TI  - Design, fabrication, and properties of macroscale supramolecular fibers consisted
      of fully hydrogen-bonded pseudo-polymer chains.
AB  - Macro-scale supramolecular fibers composed of hydrogen bonded pseudo-polymer
      chains of guanosine derivatives were fibricated, and physical properties of the
      fibers were investigated.

PMID- 12240336
TI  - Electrochemical properties of self-assembled monolayers of tripod-shaped
      molecules and their applications to organic light-emitting diodes.
AB  - Self-assembled monolayers of a tripod-shaped conjugated-thiol grafted onot
      Au(111) substrates are found to show electrochemically reversible oxidation and
      reduction and to improve electroluminescence performances of organic light
      emitting diodes.

PMID- 12240335
TI  - Evidence for oxidation at C-3 of the flavonoid C-ring during anthocyanin
      biosynthesis.
AB  - Evidence is presented for initial oxidation at the C-3 position of the flavonoid
      C-ring and for two bifurcating steps during catalysis by anthocyanidin synthase.

PMID- 12240338
TI  - Photophysics of phenyleneethynylene metal-organic oligomers. Probing the lowest
      excited state by time-resolved IR spectroscopy.
AB  - The long-lived excited state in a series of metal-organic phenyleneethynylene
      oligomers is probed by UV-visible and infrared transient absorption spectroscopy.

PMID- 12240337
TI  - Reversible activity changes of lipid-coated lipase for enantioselective
      esterification in supercritical fluoroform.
AB  - Enzymatic activity of a lipid-coated lipase for enantioselective esterification
      of (R)-1-phenylethanol in supercritical fluoroform can be reversibly controlled
      by changing pressure or temperature that reflects changes of dielectric constant.

PMID- 12240339
TI  - Modular fluorescence sensors for saccharides.
AB  - Modular and modular polymer supported fluorescence photoinduced electron transfer
      (PET) sensors 2 and 3 with two boronic acid receptor units, a pyren-1-yl
      fluorophore, and hexamethylene linker show selective saccharide binding in
      aqueous methanolic solution at pH 8.21.

PMID- 12240340
TI  - Deoligomerization of siloxanes with dimethyl carbonate over solid-base catalysts.
AB  - Hexamethyldisiloxane and hexamethylcyclotrisiloxane were almost completely
      deoligomerized with dimethyl carbonate over alumina-supported potassium fluoride
      catalyst to form methoxytrimethylsilane (85% yield) and dimethoxydimethylsilane
      (94% yield), respectively, and moreover the addition of a small amount of
      methanol to the hexamethyldisiloxane deoligomerization reaction enhanced the
      methoxytrimethylsilane yield to 98%.

PMID- 12240341
TI  - Platinum- and palladium-catalysed Kocheshkov redistribution of dialkyltin
      dichlorides or tetraalkyltins with tin tetrachloride.
AB  - The Kocheshkov redistribution reaction of tetraalkyltin or dialkyltin dichlorides
      with tin tetrachloride is effectively catalysed by platinum(II) or palladium(II)
      phosphine complexes, yielding alkyltin trichlorides in high yield and with high
      selectivity.

PMID- 12240342
TI  - Lewis acid catalysis in a supercritical carbon dioxide (scCO2)-poly(ethylene
      glycol) derivatives (PEGs) system: remarkable effect of PEGS as additives on
      reactivity of Ln(OTf)3-catalyzed Mannich and aldol reactions in scCO2.
AB  - Use of poly(ethylene glycol) derivatives (PEGs) as additives in supercritical
      carbon dioxide (scCO2) was found to be effective for Mannich and aldol reactions
      of silyl enolates with aldehydes and imines, and formation of emulsions was
      observed in these systems.

PMID- 12240343
TI  - Evidence that the availability of an allylic hydrogen governs the
      regioselectivity of the Wacker oxidation.
AB  - The allylic hydrogen is found to have a dramatic effect on the regioselectivity
      of the Wacker oxidation, leading to the postulation that an agostic hydrogen or
      enyl (sigma + pi) complex helps to stabilise the key intermediate.

PMID- 12240344
TI  - Perfluoroaryl boryl complexes: synthesis, spectroscopic and structural
      characterisation of a complex containing the bis(pentafluorophenyl)boryl ligand.
AB  - The synthesis, spectroscopic and structural characterisation of the
      bis(pentafluorophenyl)boryl derivative CpFe-(CO)2B(C6F5)2 are reported.

PMID- 12240345
TI  - Tetrathiafulvalene-acetylene scaffolding: new pi-electron systems for advanced
      materials.
AB  - Novel extended tetrathiafulvalenes (TTFs) with hexa-2,4-diyne-1,6-diylidene
      spacers between the two 1,3-dithiole rings and laterally appended alkynyl
      moieties for one- and two-dimensional scaffolding were synthesised and
      investigated for their electronic properties.

PMID- 12240346
TI  - A 3,12-connected vertice sharing adamantoid hydrogen bonded network featuring
      tetrameric clusters of cyclotriveratrylene.
AB  - The crystalline supramolecular complex [Sr(H2O)8][(CH3CN) [symbol: see text]
      (CTV)]4(H2O)4[Co(C2B9H11)2]2 features [(CH3CN) [symbol: see text] (CTV)] host
      guest interactions, back-to-back tetrameric clusters of CTV host molecules and an
      extensive hydrogen bonding giving a 3,12-connected net.

PMID- 12240347
TI  - Serine octamer metaclusters: formation, structure elucidation and implications
      for homochiral polymerization.
AB  - Multiply charged serine metaclusters (composed of two or more homochiral
      octameric units) are generated by electrospray ionization, and their unique fused
      structures (hydrogen-bonded through the sticky ends of the drum-shaped octameric
      units) have been elucidated using tandem mass spectrometry experiments and
      molecular mechanics calculations.

PMID- 12240348
TI  - Interpenetration in [Cd(isonicotinate)2(1,2-bis(4-pyridyl)-ethane)0.5(H2O)]n, a
      novel octahedral polymer containing an unusual two-dimensional bilayer motif
      generated by self-assembly of rectangle building blocks.
AB  - A hydrothermally synthesized mixed-ligand molecular solid composed of pillared
      bilayers has been formulated; it presents a new remarkable three-dimensional
      architecture sustained by the catenation of two-fold decked layers, and exhibits
      intense photoluminescence upon photoexcitation at 314 nm.

PMID- 12240349
TI  - Solid state evidence for pi-complexation of sodium cation by carbon-carbon double
      bonds.
AB  - Solid state evidence shows that neutral double bonds, attached to flexible
      sidearms of a lariat ether, serve as intramolecular pi-donors for a ring-bound
      Na+ cation.

PMID- 12240350
TI  - Artificial molecular-level machines. Dethreading-rethreading of a pseudorotaxane
      powered exclusively by light energy.
AB  - The reversible light-driven dethreading-rethreading of a pseudorotaxane is
      obtained in solution by exploiting the (E)-(Z) photoisomerisation of azobenzene,
      and monitored through fluorescence signals.

PMID- 12240351
TI  - 1-butyl-3-methylimidazolium cobalt tetracarbonyl [bmim][Co(CO)4]: a catalytically
      active organometallic ionic liquid.
AB  - An ambient temperature liquid transition metal carbonyl anion has been prepared
      in a metathesis reaction between [bmim]Cl ([bmim]+ = 1-butyl-3-methylimidazolium
      cation) and Na[Co(CO)4]; the ionic liquid catalyses the debromination of 2
      bromoketones.

PMID- 12240352
TI  - First photosensitized enantiodifferentiating isomerization by optically active
      sensitizer immobilized in zeolite supercages.
AB  - Enantiodifferentiating photoisomerization of (Z)-cyclooctene sensitized by (R)-
      or (S)-1-methylheptyl benzoate immobilized in zeolite supercages afforded the
      respective enantiomer pair, (-)- and (+)-(E)-isomer (1E) in 5% enantiomeric
      excess, whilst racemic 1E was obtained upon homogeneous-phase photosensitization
      with the same antipodal sensitizer pair, thus demonstrating for the first time
      that chirally modified zeolites not only serve as supramolecular photosensitizing
      media but also enhance the original enantiodifferentiating ability of chiral
      photosensitizer.

PMID- 12240353
TI  - Gallium-boron donor-acceptor bonds.
AB  - Examples of compounds with gallium-boron donor-acceptor bonds, HC[MeC(2,6
      pri2C6H3)N]2Ga-->B(C6F5)3 3 and (eta 5-C5Me5)Ga-->B(C6F5)3 4 have been prepared
      by treatment of the free gallanediyls with B(C6F5)3; the structures of both
      compounds were determined by X-ray crystallography.

PMID- 12240354
TI  - Dissolution of uranium dioxide in supercritical fluid carbon dioxide.
AB  - Uranium dioxide can be dissolved in supercritical CO2 with a CO2-philic TBP-HNO3
      complexant to form a highly soluble UO2(NO3)(2).2TBP complex; this new method of
      dissolving UO2 that requires no water or organic solvent may have important
      applications for reprocessing of spent nuclear fuels and for treatment of nuclear
      wastes.

PMID- 12240355
TI  - Ruthenium(III) readily abstracts NO from L-arginine, the physiological precursor
      to NO, in the presence of H2O2. A remarkably simple model system for NO
      synthases.
AB  - Reaction of [Ru(Hedta)Cl]- with H2O2 in the presence of arginine, produces NO, in
      the form of an Ru(II)-(NO+) complex and citrulline which is a remarkably simple
      model system for the physiological NO synthase reaction.

PMID- 12240356
TI  - Self-assembled bismuth nanocrystallites.
AB  - Using a high-temperature organic solution reduction method, highly crystalline
      and single domain bismuth nanoparticles have been synthesized and self-assembled.

PMID- 12240357
TI  - Detection of ppm quantities of gaseous SO2 by o9rganoplatinum dendritic sites
      immobilised on a quartz microbalance.
AB  - Sensor devices for the detection of low quantities of SO2 gas have been
      constructed which comprise organoplatinum receptor sites for the selective
      recognition of SO2 and a quartz crystal microbalance for the detection of small
      mass changes at the receptor sites.

PMID- 12240358
TI  - Lewis base effects in the Baylis-Hillman reaction of imines with cyclohex-2-en-1
      one and cyclopent-2-en-1-one.
AB  - In the Baylis-Hillman reaction of N-benzylidene-4-methyl-benzenesulfonamide with
      cyclohex-2-en-1-one or cyclopent-2-en-1-one, we found that, in the presence of a
      catalytic amount of DMAP, the Baylis-Hillman reaction can be greatly accelerated
      to give the normal Baylis-Hillman adduct 1 or 3 in good or very high yields:
      moreover, using PBu3 as a Lewis base in the reaction of N-benzylidene-4
      methylbenzenesulfonamide with cyclopent-2-en-1-one, the normal Baylis-Hillman
      adducts 3 could be obtained in very high yields within 5 h, however, using PBu3
      or DBU as a Lewis base in the reaction of N-benzylidene-4-methyl
      benzenesulfonamide with cyclohex-2-en-1-one, beside the normal Baylis-Hillman
      adduct 1 abnormal Baylis-Hillman adduct 3-aryl-2-[(4-methylphenyl)sulfonyl]-2
      azabicyclo[2.2.2]octan-5-one 2 was formed at the same time; the substituent's
      effects were also examined.

PMID- 12240359
TI  - Diels-Alder cycloaddition of novel buta-1,-3-diene derivatives possessing a
      (diethoxyphosphinoyl)difluoromethyl unit.
AB  - A series of new buta-1,3-diene derivatives possessing a
      (diethoxyphosphinoyl)difluoromethylene unit at the terminal carbon was prepared
      to examine the reactivity for Diels-Alder cycloaddition with various
      representative dienophiles.

PMID- 12240360
TI  - Palladium-iminophosphine-catalysed carbostannylation of arynes: synthesis of
      ortho-substituted arylstannanes.
AB  - Arynes were found to insert into a carbon-tin bond of alkynyl- and vinylstannanes
      in the presence of a catalytic amount of a palladium-iminophosphine complex to
      afford ortho-substituted arylstannanes, which were convertible into a wide
      variety of 1,2-disubstituted arenes via carbon-carbon bond forming reactions.

PMID- 12240361
TI  - Iodide-to-cation charge-transfer bands as a novel probe for evaluation of actual
      acceptor strengths of cations in zeolites and cation-dependent pore volume
      change.
AB  - Iodide-to-cation charge-transfer (ITC-CT) bands have been measured for the first
      time in zeolites X and Y exchanged with a series of alkali metal ions and the
      results show that the ITC-CT band progressively red shifts with increasing the
      size and the number of site III cations in the supercage, which indicates that
      the actual acceptor strength of the cation toward iodide increases with
      increasing the degree of protrusion of the cation into supercages and the number
      of cations, and overall, with decrease in supercage volume.

PMID- 12240363
TI  - Vitamin C induced decomposition of lipid hydroperoxides: direct evidence of
      genotoxin-DNA binding detected by QCRS.
AB  - We report direct evidence for human DNA-binding to precursors of mutagenic lesion
      inducing compounds, produced form the vitamin C induced decomposition of lipid
      hydroperoxides, using a quartz crystal resonant sensor assay.

PMID- 12240362
TI  - Dodeca(carboranyl)-substituted closomers: toward unimolecular nanoparticles as
      delivery vehicles for BNCT.
AB  - The syntheses of the dodeca(carboranyl)-substituted closomers, dodeca[7-(2-methyl
      1,2-dicarba-closo-dodecaboran-1-yl)heptanoate]-closo- dodecaborate(2-) and
      dodeca[7-(8-methyl-7,8-dicarba-nido-dodecaboran-7-yl)- heptanoate]-closo
      dodecaborate(14-) are reported. These boron-rich, unimolecular nanospheres
      possess great potential for future use as drug-delivery platforms for boron
      neutron capture therapy (BNCT).

PMID- 12240364
TI  - Palladium-catalysed intramolecular annulation of 2-haloanilines and ketones:
      enolate arylation vs. nucleophilic addition to the carbonyl group.
AB  - Two alternative annulation pathways involving either the enolate arylation or the
      addition to the ketone carbonyl group can operate in the Pd-catalysed
      intramolecular coupling of 2-haloanilines and ketones.

PMID- 12240365
TI  - Hydrogen bonded calixarene capsules kinetically stable in DMSO.
AB  - Half-life times up to 4 days in DMSO at room temperature are observed for the
      decomposition of dimeric capsules of urea substituted calix[4]arenes held
      together by a combination of hydrogen bonds, mechanical entanglement and cation
      pi interactions.

PMID- 12240366
TI  - Total synthesis of the novel tricyclic sesquiterpene sulcatine G.
AB  - A synthetic approach to the tricyclic sesquiterpene sulcatine G, 2, bearing a
      novel tricyclo[6.2.0.2(2,6)]decane framework, from commercially available 1,5-cod
      and leading to the first total synthesis of the natural product is described.

PMID- 12240367
TI  - A new synthesis of 1-chloroalkynes.
AB  - 4-Unsubstituted isoxazolinones derived from the corresponding beta-ketoesters can
      be chlorinated and converted into 1-chloroalkynes upon treatment with sodium
      nitrite and ferrous sulfate in aqueous acetic acid.

PMID- 12240368
TI  - Recent developments in the chemistry, biology and medicine of the epothilones.
AB  - The epothilones have occupied center stage on the scenes of total synthesis,
      chemical biology and medicine for the last five years, no doubt because of their
      intriguing mode of action and unusually high potency against tumor cells,
      including multidrug-resistant cell lines. This article highlights the most recent
      advances within this exciting field. Thus, an overview of recent synthetic
      endeavors culminating in a new generation of total syntheses and analogues, some
      with higher potencies than the naturally occurring substances, will be given, and
      the chemical biology, in particular the current understanding of structure
      activity relationships of the epothilones, will also be discussed in light of the
      latest biological results. In addition, the recently elucidated biosynthetic
      machinery of the natural epothilone-producing myxobacterium Sorangium cellulosum,
      as it is now understood, will be described. Finally, some preclinical and
      clinical studies will be summarized.

PMID- 12240369
TI  - A new palladium-catalysed synthesis of 1,1-dialkylbuta-1,3-dienes via organoboron
      intermediates.
AB  - Iodobenzene and tetrakis(triphenylphosphine)palladium(0) [(C6H5)3P]4Pd catalyse a
      new synthesis of 1,1-dialkylbuta-1,3-dienes, starting from 1,1-diethoxybut-2-ene
      and trialkylboranes, in the presence of Schlosser's superbase LIC-KOR.

PMID- 12240370
TI  - Direct observation of light induced spin transitions in new 3,5-bis(2
      pyridyl)pyrazolato bridged thiocyanato diiron(II) complexes by monitoring
      variable temperature laser Raman spectra.
AB  - The light induced excited spin state trapping LIESST and the reverse LIESST-like
      phenomena are observed below and above the spin transition temperature,
      respectively, for new dinuclear diiron(II) complexes and familiar Fe(II)
      complexes with thiocyanate ligands by monitoring the Raman spectra where only
      excitation light of various wavelengths for the spectroscopy was used without
      extra excitation light sources.

PMID- 12240371
TI  - Highly active catalysts for the Suzuki coupling of aryl chlorides.
AB  - Simple tricyclohexylphosphine adducts of palladium complexes with orthometallated
      N-donor ligands show by far the highest activity yet reported in the Suzuki
      coupling of aryl chlorides, even under aerobic conditions.

PMID- 12240372
TI  - Tuning metal coordination number by ancillary ligand steric effects: synthesis of
      a three-coordinate iron(II) complex.
AB  - The coordination number of the metal in iron(II) beta-diketiminate complexes can
      be tuned through the size of the alkyl substituents on the ligand backbone.

PMID- 12240373
TI  - Ultrasound promoted C-C bond formation: Heck reaction at ambient conditions in
      room temperature ionic liquids.
AB  - Heck reaction proceeds at ambient temperature (30 degrees C) with considerably
      enhanced reaction rate (1.5-3 h) through the formation of Pd-biscarbene complexes
      and stabilized clusters of zero-valent Pd nanoparticles in ionic liquids under
      ultrasonic irradiation.

PMID- 12240374
TI  - Asymmetric trialkylaluminium addition to aldehydes catalyzed by titanium
      complexes of N-sulfonylated amino alcohols with two stereogenic centers.
AB  - The asymmetric methylation, ethylation and allylation of aldehydes using
      trialkylaluminium reagents catalyzed by titanium(IV) complexes of N-sulfonylated
      amino alcohols gave excellent enantioselectivities of up to 99% ee.

PMID- 12240375
TI  - A comparison of the pentaammine(pyridyl)ruthenium(II) and 4-(dimethylamino)phenyl
      groups as electron donors for quadratic non-linear optics.
AB  - Hyper-Rayleigh scattering and Stark spectroscopic studies show that the complex
      salts [1-4]PF6 have larger static first hyperpolarizabilities beta 0 than [5
      8]PF6, because the higher HOMO energy of a (RuII(NH3)5)2+ centre more than
      offsets the superior pi-orbital overlap in the purely organic chromophores.

PMID- 12240376
TI  - A new stabilised form of isobenzofuran, rack-mounted on an alicyclophane.
AB  - New stable, crystalline isobenzofurans 9a and 9b linked through the 1,3-positions
      and incorporated into alicyclophanes have been prepared from the related
      furanoalicyclophane 5 in three steps (i) addition of benzyne or 4,5
      bis(trimethylsilyl)benzyne (ii) hydrogenation of the pi-bond (iii) ejection of
      ethylene by flash vacuum pyrolysis, and shown to yet retain high 1,3-diene
      character and form adducts with dienophiles, e.g. dimethyl acetylenedicarboxylate
      or N-methyl maleimide; the corresponding off-rack 1,3-dimethylisobenzofurans were
      too unstable for isolation.

PMID- 12240377
TI  - Synthetic study of phomoidride B (CP-263,114); utilization of the oxidopyrylium
      [5 + 2] cycloaddition.
AB  - The highly functionalized core structure of phomoidride B (CP-263,114) was
      pursued by using intermolecular oxidopyrylium-alkene cyclization as one of the
      key steps.

PMID- 12240378
TI  - Self-assembled nanoscale capsules between resorcin[4]arene derivatives and Pd(II)
      Pt(II) complexes.
AB  - Nanoscale molecular capsules have been prepared by self-assembly of resorcin[4]
      arene derivatives and Pd(II) or Pt(II) complexes; the positively charged N
      alkylpyridinium derivatives are encapsulated inside capsules due to strong cation
      pi interactions.

PMID- 12240379
TI  - Self-assembled organogels formed by mono-chain L-alanine derivatives.
AB  - The mono-chain L-alanine derivatives self-assemble into bilayer aggregates in a
      number of organic liquids and gelatinize the liquids.

PMID- 12240380
TI  - A regioselective cycloaddition route to isoxazoleboronic esters.
AB  - Alkynylboronates participate in 1,3-dipolar cycloaddition reactions with nitrile
      oxides to provide isoxazoleboronic esters with excellent levels of regiocontrol;
      additionally, these potentially valuable synthetic intermediates have been shown
      to participate efficiently in Suzuki coupling reactions.

PMID- 12240381
TI  - Cerium masquerading as a group 4 element: synthesis, structure and computational
      characterisation of [CeCl(N(SiMe3)2)3].
AB  - Oxidation of the three-coordinate cerium amide [Ce(N-(SiMe3)2)3] with TeCl4 in
      toluene solution yields purple, diamagnetic [CeCl(N(SiMe3)2)3], whose structure
      has been examined by X-ray crystallographic and computational methods.

PMID- 12240382
TI  - Mono- and di-nickellaazaphosphiranes of mono- and bis
      (amido)cyclodiphosph(III)azanes.
AB  - The syntheses and solid-state structures of the first three-membered nickel
      phosphorus-nitrogen ring compounds, having anionic four-electron P=N moieties are
      reported.

PMID- 12240383
TI  - NMR evidence of pentaoxo organosilicon complexes in dilute neutral aqueous
      silicate solutions.
AB  - Silicon-29 NMR spectra of a neutral, dilute aqueous silicic acid solution, with a
      pH and Si concentration typical of soil solutions, reveal that a significant
      fraction of the silicon is incorporated in two five-coordinated organosilicon
      complexes when sodium gluconate is present.

PMID- 12240384
TI  - Non-catalytic and selective alkylation of phenol with propan-2-ol in
      supercritical water.
AB  - Phenol can be alkylated with propan-2-ol without catalyst in supercritical water
      at 673 K with mainly ortho substituted alkylphenols being obtained and alkylation
      reaction rate increasing with increasing water density.

PMID- 12240385
TI  - Rhodizonate and croconate dianions as divergent hydrogen-bond acceptors in the
      self-assembly of supramolecular structures.
AB  - The C5O5(2-) and relatively unstable C6O6(2-) dianions, each serving as a hub for
      binding with a set of convergent NH donor groups of four phenylurea molecules,
      have been generated in situ and stabilized in nearly isostructural hydrogen
      bonded host lattices.

PMID- 12240386
TI  - A remarkable temperature-dependent, accidental degeneracy of 31P NMR chemical
      shifts in Ru(II) diphosphine/diimine complexes.
AB  - Several cis-RuX2((R)-BINAP)(diimine) complexes have been prepared, and many of
      these exhibit an unusual temperature-dependent, accidental degeneracy of the 31P
      shifts in their solution NMR spectra.

PMID- 12240387
TI  - Assembling the biosynthetic puzzle of crucifer metabolites: indole-3-acetaldoxime
      is incorporated efficiently into phytoalexins but glucobrassicin is not.
AB  - First biosynthetic studies utilizing tetradeuterated precursors indicate that the
      indole glucosinolate glucobrassicin is not a precursor of the phytoalexin
      brassinin, and that indole-3-acetaldoxime is an efficient precursor.

PMID- 12240388
TI  - Dual-mode electrochromism switched by proton transfer: dynamic redox properties
      of bis(diarylmethylenium)-type dyes.
AB  - Upon oxidative dimerization of pale yellow Ar2C=CHPh 1 (Ar = 4-Me2NC6H4), deep
      blue 1,4-dication 2(2+) was obtained as a stable salt, which was transformed into
      1 by reductive C-C bond fission; deprotonation of 2(2+) gave intense yellow diene
      3, which was interconvertible with violet dication 4(2+) by two-electron
      transfer, thus exhibiting two distinct modes of electrochromism before and after
      proton transfer.

PMID- 12240389
TI  - Efficient radical addition of tertiary amines to electron-deficient alkenes using
      semiconductors as photochemical sensitisers.
AB  - Tertiary amines can be added to electron-deficient alkenes with yields up to 98%
      in a radical chain reaction initiated by a photochemical electron transfer using
      inorganic semiconductors like TiO2 as sensitiser.

PMID- 12240390
TI  - The structure dependent electrochemical-response of novel 1-(4-mercaptobutyl)-4
      (2-ferrocenylvinyl)pyridinium bromide SAMs on an au electrode.
AB  - The 1-(4-mercaptobutyl)-4-(2-ferrocenylvinyl)pyridinium bromide (1-HS(CH2)(4)-4
      [(E)-FcCH=CH]C5H4N)+Br- and its hydrogenated product [1-HS(CH2)(4)-4-(
      FcCH2CH2)C5H4N]+Br- were synthesized and assembled on an Au electrode to form
      self-assembled monolayers which showed a structure-dependent electrochemical
      response in phosphate buffer aqueous solutions (pH = 7).

PMID- 12240391
TI  - Disruption of protein-protein interactions: design of a synthetic receptor that
      blocks the binding of cytochrome c to cytochrome c peroxidase.
AB  - Synthetic receptor 1 has been found via fluorescence titration to compete
      effectively with cytochrome c peroxidase for binding cytochrome c (Cc), forming
      1:1 Cc:1 complex with a binding constant of (3 +/- 1) x 10(8) M-1, and to disrupt
      Cc: Apaf-1 complex, a key adduct in apoptosis.

PMID- 12240392
TI  - Design and post-functionalisation of ordered mesoporous zirconia thin films.
AB  - Bidimensional hexagonal or centred-rectangular mesoporous zirconia thin films
      have been reproducibly prepared by evaporation-induced self-assembly (EISA),
      which are stable up to 300 degrees C, with pore size around 35 A; the films can
      be post-functionalised with organic ligands presenting different functions,
      opening a land of opportunities for the design of new hybrid mesostructured
      materials, based on the synergy of a transition metal oxide network and organic
      groups.

PMID- 12240393
TI  - Synthesis and structure of the novel mixed anion-dianion lithium cage compound
      [(6-LiCH2Py-2-OLi)4(6-CH3Py-2-OLi)2(THF)9].
AB  - The title compound crystallises as a novel homometallic mixed anion-dianion cage
      incorporating two four-coordinate diorgano lithiate centres, in addition to eight
      lithium centres coordinated only by oxygen and nitrogen atoms.

PMID- 12240394
TI  - Novel octahedral tungsten sulfidocyanide cluster anion [W6S8(CN)6]6-.
AB  - Novel tungsten octahedral sulfidocyanide cluster compounds Na6[W6S8(CN)6].18DMSO
      1 and K6[W6S8(CN)6] 2 have been synthesized and characterized by X-ray
      crystallography and NMR spectroscopy.

PMID- 12240395
TI  - Photoreactivity of ETS-10.
AB  - Irradiation of H-ETS-10 in the presence of adsorbed methanol or ethene causes
      photoreduction of Ti(IV) to Ti(III); photoreduction does not occur for Na, K-ETS
      10, but a photoinduced polymerization of ethene is observed.

PMID- 12240396
TI  - Design and synthesis of a new bicyclic dipeptide isostere.
AB  - The synthesis of a new Gly-Pro turn mimetic and the computational study of its
      ability to induce beta-turn is reported.

PMID- 12240397
TI  - Self-assembly of a bis-urea macrocycle into a columnar nanotube.
AB  - A bis-urea macrocycle 1 was synthesized and shown to form extended nanotubular
      columns by X-ray crystallography.

PMID- 12240398
TI  - A multi-component coupling approach to benzo[b]furans and indoles.
AB  - A single step access to multiply substituted benzo[b]furans and indoles has been
      developed.

PMID- 12240399
TI  - Enantioselective Michael addition of beta-keto esters to methyl vinyl ketone
      employing a chiral N,N'-dioxide-scandium trifluoromethanesulfonate complex as a
      catalyst.
AB  - An enantioselective Michael addition of beta-keto esters to methyl vinyl ketone
      exploiting a chiral N,N'-dioxide-scandium trifluoromethanesulfonate complex as a
      catalyst affords the corresponding Michael adducts in high yields and with
      enantioselectivities of up to 80% ee.

PMID- 12240400
TI  - Intercalation of a pendant-arm tetraazamacrocycle into molybdenum disulfide.
AB  - A novel macrocycle-MoS2 nanocomposite has been synthesized and characterized
      using the exfoliation/restacking properties of LiMoS2, providing the first of a
      new family of intercalation compounds.

PMID- 12240401
TI  - Tandem anionic Michael addition/radical cyclizations: a new and efficient
      strategy for the synthesis of functionalized cyclopentanes.
AB  - The combination of anionic Michael addition of lithium ester enolates with
      radical 5-exo cyclizations through SET oxidation gives highly functionalized
      cyclopentanes.

PMID- 12240403
TI  - Catalytic asymmetric synthesis of 1,1'-spirobi[indan-3,3'-dione] via a double
      intramolecular C-H insertion process.
AB  - A highly efficient one-pot construction of optically active 1,1'-spirobi[indan
      3,3'-dione] derivative (up to 80% ee) has been achieved by exploiting the double
      intramolecular C-H insertion reaction of dimethyl 2,2'-methylenebis(alpha-diazo
      beta-oxobenzenepropanoate) under the influence of dirhodium(II) tetrakis[N
      phthaloyl-(R or S)-tert-leucinate] as a catalyst.

PMID- 12240402
TI  - Synthesising protease-stable isopeptides by proteases: an efficient biocatalytic
      approach on the basis of a new type of substrate mimetics.
AB  - A biocatalytic route to the 'post-synthesis' formation of Asp/Glu-derived
      isopeptides is illustrated on the basis of the Staphylococcus aureus V8 protease
      used as the biocatalyst, a new type of substrate mimetics as the donor peptides,
      and several acceptor peptides varying in length and sequence.

PMID- 12240404
TI  - A tandem allylsilane-vinylsilane difunctionalization by silylcupration of allene
      followed by reaction with alpha,beta-unsaturated nitriles.
AB  - Silylcupration of allene using phenyldimethylsilylcopper 1 followed by BF3
      mediated reaction with alpha,beta-unsaturated nitriles at -40 degrees C affords
      allylsilane-vinylsilane-containing ketones resulting from consecutive addition
      (1,2 and 1,4) of the intermediate allyl- and vinylcopper species formed in the
      silylcupration of allene.

PMID- 12240406
TI  - Electrochemical evidence for electronic interactions through the para-carborane
      skeleton in the novel tricluster [(Co2C2(SiMe3)(CO)4(dppm))2(mu-CB10H10C)].
AB  - The electrochemical properties of the title compound reveal electronic
      interactions between two dicobalt-dicarbon clusters via a 1,12-para-carborane
      cage.

PMID- 12240405
TI  - Alizarin Red S. as a general optical reporter for studying the binding of boronic
      acids with carbohydrates.
AB  - Alizarin Red S. displays a dramatic change in fluorescence intensity and color in
      response to the binding of a boronic acid and can be used as a general reporter
      for studying carbohydrate-boronic acid interactions, both quantitatively and
      qualitatively.

PMID- 12240407
TI  - A remarkable rate acceleration of the Baylis-Hillman reaction.
AB  - Treatment of alpha-naphthyl acrylate with both aliphatic and aromatic aldehydes
      in the presence of DABCO (30 mol%) afforded the desired (alpha-methylene-beta
      hydroxy)esters with reasonable chemical yields (51-88%) within 20 min.

PMID- 12240408
TI  - Positive and negative photopatterning of metal oxides on silicon via bipolar
      electrochemical deposition.
AB  - Negative and positive microscale patterning of metal oxides is efficiently and
      rapidly carried out on flat Si(100) surfaces via a simple white light assisted
      bipolar electrochemical process.

PMID- 12240410
TI  - A novel precipitating auxiliary approach to the purification of Baylis-Hillman
      adducts.
AB  - Diaryl alkene alcohol 1 is a 'precipiton', a precipitating auxiliary that is used
      to aid the isolation of Baylis-Hillman adducts.

PMID- 12240409
TI  - The effect of the primary structure of the polypeptide catalyst on the
      enantioselectivity of the Julia-Colonna asymmetric epoxidation of enones.
AB  - Epoxidation of chalcone (1), using basic hydrogen peroxide, catalysed by
      polypeptides with defined primary structures demonstrates that the residues in
      the chain near to the N-terminus determine the stereochemical outcome of the
      reaction.

PMID- 12240411
TI  - Attenuation of Hofmeister bias in ion-pair extraction by a disulfonamide anion
      host used in strikingly effective synergistic combination with a calix-crown Cs+
      host.
AB  - A calix-crown/disulfonamide dual-host combination in 1,2-dichloroethane exhibits
      markedly enhanced ion-pair extraction of caesium salts, with the observed
      synergism following an anti-Hofmeister order.

PMID- 12240412
TI  - Selective recovery of solutes from ionic liquids by pervaporation--a novel
      approach for purification and green processing.
AB  - Non-porous membranes with the selective layer consisting of hydrophilic or
      hydrophobic polymers have been applied for the quantitative and selective
      recovery of solutes with different physico-chemical properties from a room
      temperature ionic liquid, ([bmim][PF6]).

PMID- 12240413
TI  - The hetero Diels-Alder reactions of masked o-benzoquinones with nitroso
      compounds.
AB  - The first examples of hetero Diels-Alder reaction of masked o-benzoquinones with
      nitroso dienophiles leading to novel and highly functionalized heterocycles,
      which are potential intermediates for nitrogenous natural products are reported.

PMID- 12240414
TI  - An ab initio study of the influence of crystal packing on the host-guest
      interactions of calix[4]arene crystal structures.
AB  - We report the first quantum mechanical calculations of p-tert-butylcalix[4]arene
      inclusion complexes in the crystalline state with geometrical aspects
      demonstrating good agreement with experiment, while comparison of the
      configurations calculated for an isolated complex and in the crystal, illustrate
      that crystal packing forces contribute to the observed structure of the host
      guest assembly.

PMID- 12240415
TI  - Synthesis and properties of novel bis(triarylamines) based on a 3,3'-diphenyl
      2,2'-bithiophene core.
AB  - An efficient synthesis of 3,3'-diphenyl-2,2'-bithiophene based bis(triarylamines)
      and their physical properties are reported.

PMID- 12240416
TI  - Highly diastereoselective dihydride formation by activation of methanol with
      IrCl((S)-binap)(PPh3).
AB  - Reaction of [IrCl((S)-binap)(PPh3)] ((S)-3) with methanol gave one of the
      diastereomers of the cis,mer-dihydride, cis,mer-OC-6-44-A-[IrCl(H2)((S)
      binap)(PPh3)] ((S)-4a) stereoselectively, the structure of which was determined
      crystallographically, whereas the reaction of (S)-3 with H2 produced a 1:1
      mixture of the diastereomers of the cis,mer-dihydride, (S)-4a and cis,mer-OC-6-44
      C-[IrCl(H2)((S)-binap)(PPh3)] ((S)-4b).

PMID- 12240417
TI  - The binding of difunctional neutral guest molecules by novel bis(tripyrrolyl)
      cryptands.
AB  - Bis(tripyrrolyl) cryptands are prepared via a [2 + 3] Schiff base condensation of
      formyltripyrrolyls with diamines; an ethyl-spaced hexapyrrole cryptand is shown
      to bind strongly ethane-1,2-diamine and ethane-1,2-diol in chloroform solution.

PMID- 12240418
TI  - Formation of the monoanion [Ar*P(BH3)(mu-BH2)2H]- with a symmetrically bridging
      hydride from the attempted synthesis of the dianion [Ar*P(BH3)3]2-.
AB  - Addition of an excess of BunLi to the bis(borano)phosphide complex [Ar*PH(BH3)2]
      Li+ 1 (Ar* = 2,4,6-tri-tert-butylphenyl) and subsequent treatment with BH3, gives
      the anionic complex [Ar*P(BH3)(mu-BH2)2H]-Li+ 2 instead of the expected
      tris(borano)phosphide dilithium, [Ar*P(BH3)3]2-2Li+ 3.

PMID- 12240419
TI  - A novel bimetallic cage complex constructed from six V4Co pentatomic rings:
      hydrothermal synthesis and crystal structure of [(2,2'-Py2NH)2Co]3V8O23.
AB  - A bimetallic cluster complex, [(2,2'-Py2NH)2Co]3V8O23 (2,2'-Py2NH = 2,2'
      dipyridylamine) 1, has been hydrothermally synthesized; X-ray crystallography
      reveals that 1 possesses a novel cage topology structure in which the metal
      cluster core is constructed from six V4Co pentatomic rings.

PMID- 12240420
TI  - Bidentate carbenoid ester coordination in ruthenium(II) Schiff-base complexes
      leading to excellent levels of diastereo- and enantioselectivity in catalytic
      alkene cyclopropanation.
AB  - Exceptionally high stereoselectivity (ee < or = 98%, dr < or = 99:1) in the
      cyclopropanation of alkenes with ethyl diazoacetate using a non-planar
      ruthenium(II) Schiff-base precatalyst is a result of eta 2C,O binding of the
      carbenoid ester intermediate, according to DFT calculations.

PMID- 12240421
TI  - The inverse podant [Li3(NBut)3S)]+ stabilises a single ethylene oxide OCH=CH2
      anion as a high- and low-temperature polymorph of [(thf)3Li3(OCH=CH2)(NBut)3S)].
AB  - A single ethylene oxide anion derived from the ether cleavage reaction of thf
      with ButLi is stabilised by the inverse podant [Li3(NBut)3S)]+ to give a high-
      and a low-temperature polymorph with a considerable difference in conformation
      and packing.

PMID- 12240422
TI  - An unusual six-co-ordinate platinum(II) complex containing a neutral I2 ligand.
AB  - The present paper deals with a rare platinum(II) complex containing the kappa-I2
      ligand, which is an unusual example of a six-co-ordinated octahedral platinum(II)
      complex.

PMID- 12240424
TI  - Local ordering of hydroxy groups in hydroxyapatite.
AB  - Density functional theory calculations of hydroxyapatite identified the oxygen
      and hydrogen positions of the hydroxy groups in the crystal structure to be well
      defined, alternating in a column in the c-direction, and we predict that the
      experimentally found oxygen and hydrogen disorder is due to the presence in the
      crystal of differently oriented locally ordered domains, a finding which is
      important for studies of crystal growth and surface reactivity.

PMID- 12240423
TI  - Nickel porphyrin nanotweezers.
AB  - A strapped chiroporphyrin free base with two 8-methylene chains linking two
      adjacent meso-substituents was synthesized as the alpha 4 conformer; insertion of
      Ni(II) triggered a complete conversion to the alpha beta alpha beta complex, and
      demetallation totally regenerated the strapped free base in the alpha 4
      conformation.

PMID- 12240425
TI  - Cs1-xSn1-xBi9+Se15 and Cs1.5-3xBi9.5+xSe15: members of the homologous superseries
      Am[M1+lSe2+l]2m[M1 + 2l+nSe3 + 3l+n] (A = alkali metal, M = Sn and Bi) allowing
      structural evolution in three different dimensions.
AB  - Cs1-xSn1-xBi9+xSe15 and Cs1.5-3xBi9.5+xSe15 crystallize in a new structure type
      which does not belong to but is closely related to the members of the homologous
      series Am[M6-Se8]m[M5+nSe9+n]; the new phases reveal a third dimension of
      structural evolution for this series according to the formula Am[M1+lSe2+l]2m[M1
      + 2l + nSe3 + 3l+n].

PMID- 12240426
TI  - Heteroanionic intercalation into positively charged inorganic hosts: the first
      nitride mixed halides.
AB  - The first nitride mixed halides have been synthesised by disordered intercalation
      of anions between the positively charged layers of subnitride hosts.

PMID- 12240427
TI  - Self-assembly of a novel macrotricyclic Pd(II) metallocage encapsulating a
      nitrate ion.
AB  - Complexation of the ligand 1 with Pd(NO3)2 leads to the self-assembly of a very
      stable M2L4 type macrotricyclic cage that encapsulates a nitrate ion inside its
      cavity.

PMID- 12240428
TI  - The activation of molecular oxygen by horseradish peroxidase with sodium sulfite.
AB  - Horseradish peroxidase (HRP) utilizes molecular oxygen (O2) with sodium sulfite
      (Na2SO3) to oxidize thioanisole and styrene at the exterior of the heme pocket.

PMID- 12240429
TI  - Reversible trans-cis photoisomerization of azobenzene-attached bipyridine ligands
      coordinated to cobalt using a single UV light source and the Co(III)/Co(II) redox
      change.
AB  - The trans/cis ratio of the azobenzene-attached bipyridine ligands in a cobalt
      complex is reversibly altered by a combination of photoirradiation with a single
      UV light source and the reversible redox change between Co(II) and Co(III).

PMID- 12240430
TI  - A novel luminescent copper(I) complex containing an acetylenediide-bridged,
      butterfly-shaped tetranuclear core.
AB  - A novel luminescent acetylenediide-bridged tetranuclear copper(I) complex [Cu4(mu
      Ph2Ppypz)4(mu 4-eta 1,eta 2-C identical to C)]-(ClO4)2 [Ph2Ppypz = 2
      (diphenylphosphino-6-pyrazol-1-yl)pyridine] has been synthesized and structurally
      characterized by X-ray crystallography.

PMID- 12240431
TI  - Subtlety in the reactivity of a diketo phosphorus ylide towards mercuric halides:
      the unprecedented O-coordination of alpha-acetyl-alpha
      benzoylmethylenetriphenylphosphorane to Hg(II).
AB  - The reactions of the title ylide with HgX2 (X = Cl, Br or I) lead to the
      regiospecific binding of the acetyl oxygen to soft Hg(II), producing a chloro
      complex with (2 + 2) coordination and isostructural dimeric bromo and iodo
      complexes containing halogen bridges with tetrahedral configurations around the
      metal centres.

PMID- 12240432
TI  - The effect of diethylamine on Stille alkylations with tetraalkylstannanes.
AB  - The addition of diethylamine to Stille alkylation reactions using stannanes
      improves yields by reducing beta-hydride elimination and reduction reactions, it
      also serves as a substitute for other additives such as Cu(I)I.

PMID- 12240433
TI  - A new Hg(2+)-selective chromoionophore based on calix[4]arenediazacrown ether.
AB  - A new azophenol type chromogenic ionophore based on the p-tert
      butylcalix[4]arenediazacrown ether was prepared: the ionophore exhibited a
      pronouncedly selective chromogenic behaviour toward Hg2+ ions among the surveyed
      guests of alkali, alkaline earth, transition and heavy metal ions in liquid
      liquid extraction experiments.

PMID- 12240434
TI  - The first bis-Rh(I) metal complex of N-confused porphyrin.
AB  - An inner- and outer-N coordinated bis-Rh(I) metal complex was obtained from the
      reaction of N-confused porphyrin and [Rh(CO)2Cl]2 in CH2Cl2 and the structure was
      confirmed by a single crystal X-ray analysis.

PMID- 12240435
TI  - Photoluminescence of open-framework phosphates and germanates.
AB  - Upon excitation by long wavelength UV radiation, strong room temperature
      luminescence is observed in a family of metal-activator-free zeolite-type
      materials; the luminescent output from the large cage UCSB-8Mg structure is
      independent of temperature from 298 K until at least 77 K.

PMID- 12240436
TI  - Dehydrogenative coupling of phenanthroline under hydrothermal conditions: crystal
      structure of a novel layered vanadate complex constructed of 4,8,10-net sheets:
      [(2,2'-biphen)Co]V3O8.5.
AB  - 2,2'-Biphenanthroline (2,2'-biphen) formed from 1,10-phenanthroline when a new
      two-dimensional layered vanadium oxide metal coordination complex, [(2,2'
      biphen)Co]V3O8.5, which contains novel 4,8,10-net sheets, was hydrothermally
      synthesized.

PMID- 12240437
TI  - Naphthalene formation by allylation of zirconaindenes in the ZnX2-Pd(PPh3)4
      system.
AB  - Zirconaindenes reacted with allyl halides in the presence of ZnX2 (X = Cl or Br)
      and a catalytic amount of Pd(PPh3)4 to give naphthalene derivatives in good
      yield.

PMID- 12240438
TI  - Powerful Claisen condensation and Claisen-aldol tandem reaction of alpha,alpha
      dialkylated esters promoted by ZrCl4-iPr2NEt.
AB  - Powerful Claisen ester condensations of alpha,alpha-dialkylated esters mediated
      by ZrCl4-iPr2NEt were performed to give the corresponding thermodynamically
      unfavorable alpha,alpha-dialkylated beta-ketoesters, and Claisen-aldol tandem
      reactions between an intermediary Zr-enolate of a alpha,alpha-dialkylated beta
      ketoester and aldehydes also proceeded.

PMID- 12240439
TI  - Niobium and vanadium iminophosphinimide complexes.
AB  - The iminophosphinimide complexes [Ar(R)N]3M(NPNBut) (M = V, Nb) were prepared
      from the corresponding anionic nitride species ([Ar(R)N]3M identical to NNa)2 by
      way of a four-step synthetic strategy.

PMID- 12240440
TI  - Trimagnesium-bridged trinuclear ferrocenophanes cocomplexed with solvated
      mononuclear alkali metal amide molecules.
AB  - Three prototypes of the remarkable new class of compound referred to in the title
      have been synthesised by treating ferrocene with the same mixed lithium (or
      sodium)-magnesium amide recipes as those used previously to make s-block metal
      inverse crowns.

PMID- 12240441
TI  - Crystal growth, structure determination and magnetism of a new hexagonal rhodate:
      Ba9Rh8O24.
AB  - Single crystals of Ba9Rh8O24, grown from a molten potassium carbonate flux,
      crystallize in the spacegroup R3c with lattice parameters of a = 10.0899(4) and c
      = 41.462(2) A. Magnetic measurements on oriented single crystals reveal the
      existence of magnetic anisotropy.

PMID- 12240442
TI  - Oxidative cyclisation of cinnamyl ethers mediated by CAN: a stereoselective
      synthesis of 3,4-trans disubstituted tetrahydrofuran derivatives.
AB  - The oxidative cyclisation of cinnamyl ethers mediated by cerium(IV) ammonium
      nitrate results in the stereospecific formation of 3,4-trans disubstituted
      tetrahydrofuran derivatives in moderate to good yields.

PMID- 12240443
TI  - Three component synthesis of oxa-bridged tetracyclic tetrahydroquinolines.
AB  - Bridged tetracyclic tetrahydroquinoline is synthesized by a novel one-pot three
      component condensation of an ortho-amino cinnamate, alpha-isocyano acetamide and
      an aldehyde.

PMID- 12240444
TI  - Synthesis of diphenylmethane from formalin and benzene in a biphasic system with
      12-tungstophosphoric acid.
AB  - Heteropoly acids such as H3PW12O40 are exceptionally active catalysts in the
      synthesis of diphenylmethane from benzene and formalin (aqueous formaldehyde) in
      a biphasic system and can be recycled simply by drying the aqueous phase at room
      temperature.

PMID- 12240445
TI  - Novel self-assembled monolayers of disulfides with bicyclo[2.2.2]octane moieties
      of Au(111).
AB  - A series of disulfides containing bicyclo[2.2.2]octane moieties have been
      synthesised and their self-assembled monolayers (SAMs) on Au(111) have been
      characterized using scanning tunnelling microscopy (STM).

PMID- 12240446
TI  - Dynamic equilibration of eta 1-carbene and eta 2-alkyne moieties within an
      alkynylcarbene dimanganese complex.
AB  - The coordination of an additional [Cp(CO)2Mn] fragment to the alkyne linkage of
      an alkynylcarbene complex of the type Cp(CO)2Mn=C(R')C identical to CR" yields a
      highly fluxional molecule, in which the [eta 1-carbene] and [eta 2-alkyne]
      moieties are seen to exchange rapidly on the NMR time scale.

PMID- 12240447
TI  - Ruthenium catalysed cross metathesis with fluorinated olefins.
AB  - The E-selective cross metathesis (CM) of fluorinated olefins with various
      functionalised alkenes in good to excellent yields is reported.

PMID- 12240448
TI  - Complex of polyelectrolyte network with surfactant as novel shape memory
      networks.
AB  - Poly(acrylic acid-co-methyl methacrylate)-cetyltrimethylammonium bromide (P(AA-co
      MMA)-C16TAB) complex has shape memory behavior due to the formation of
      crystalline aggregates among the long alkyl chains of C16TAB in the complex, and
      can be regarded as a novel shape memory network.

PMID- 12240449
TI  - Nafion-H catalysed sulfonylation of aromatics with arene/alkenesulfonic acids for
      the preparation of sulfones1a.
AB  - Synthesis of both symmetric and unsymmetric diaryl/aryl alkyl sulfones is easily
      achieved by Friedel-Crafts type sulfonylation of aromatics with suitable arene-
      or alkane-sulfonic acids in the presence of Nafion-H, a perfluorinated
      resinsulfonic acid catalyst.

PMID- 12240450
TI  - Lanthanide triflate-catalyzed three component synthesis of alpha-amino
      phosphonates in ionic liquids. A catalyst reactivity and reusability study.
AB  - The catalyst reactivity and reusability for the lanthanide triflate-catalyzed
      three component synthesis of alpha-amino phosphonates have been examined in room
      temperature ionic liquids, [bmim][X], in which the catalytic activities were very
      dependent on the counter anion, X, as well as on the phosphorus nucleophile, and
      moreover, the catalyst immobilized in an ionic liquid was reused several times
      without any loss of activity.

PMID- 12240452
TI  - Managing our first breaths: a reflection on the past several decades of neonatal
      pulmonary therapy.
AB  - Lung disease has been a leading cause of significant morbidity and mortality
      since neonates first drew breath. Over the past few decades, many treatment
      options have evolved to aid us in our ability to support neonatal breathing. The
      history of neonatal pulmonary care, both its successes and controversies, can
      teach us a great deal about the future of this dynamic field. As new developments
      occur, we constantly modify the therapies we offer to preterm and term infants.
      Understanding traditional therapeutic options and knowing what may be on the
      horizon can help caregivers to better match treatment plans with individual
      infants. This article reviews advances in mechanical ventilation, adjuvant
      therapies, and respiratory drugs through the past few decades and speculates on
      future directions in this field.

PMID- 12240453
TI  - The history of neonatal resuscitation.
AB  - Attempts at human resuscitation date back to ancient times. Most strategies for
      resuscitation focused on adults until the early 1800s, when newborn resuscitation
      captured the interest of noted practitioners. The most promising techniques and
      strategies for neonatal resuscitation were developed during the latter part of
      the twentieth century. This article examines the key components of neonatal
      resuscitation and the discoveries that stimulated the development of current
      neonatal resuscitation practices.

PMID- 12240454
TI  - Best evidence-based practices: a historic perspective.
AB  - Neonatologists, neonatal nurses, and others who care for critically ill newborns
      hope that the care they provide will improve the health and the
      neurodevelopmental outcome of these neonates. In this progressive era of neonatal
      medicine, we must pause to look backward even as we look forward, taking full
      advantage of the opportunity to reflect on our short history and to review
      several important events in neonatal medicine that have contributed in a
      meaningful way to the evolution of evidence-based neonatal care. Six
      interventions highlight why randomized controlled trials are necessary to
      understand the risks and benefits of our interventions with premature and
      critically ill infants. We hope this history of the evolving practice of evidence
      based neonatal care will enable the reader to have a greater appreciation for the
      consideration of each and every intervention that we take on behalf of the
      infants in our care.

PMID- 12240455
TI  - Some pain, some gain: reflections on the past two decades of neonatal pain
      research and treatment.
AB  - This review reflects back on the progress that has been made in infant pain
      research over the past 20 years and how the research has influenced (or has
      failed to influence) the attitudes and practices of health professionals about
      infant pain. Progress in understanding of infant pain neurobiology, treatment,
      and measurement are discussed, and new directions for future research are
      proposed.

PMID- 12240456
TI  - Advances in neonatal care: focusing on the last 20 years.
AB  - This article is a collaborative effort of five nurses who have worked together
      for a total of 173 collective years. We have experienced vast changes in the
      field of neonatology during the last 40 years and wish to share some of the
      significant developments as we experienced them in our unit. We realize that the
      various changes differ by location and institution.

PMID- 12240457
TI  - The history of the neonatal nurse practitioner: reflections from "under the
      looking glass".
AB  - The neonatal nurse practitioner (NNP) emerged in the 1970s. During the first two
      decades, nurses who functioned in this new advanced-practice role were forced to
      overcome interprofessional isolation, variable educational preparation,
      underutilization, and title ambiguity. However, after nearly 30 years of
      evolution influenced by the changing health care environment, technological
      advancements in newborn care, medical personnel shortages, and the advanced
      practice nurse movement, the NNP is now a recognized member of the neonatal
      health care team nationwide. The NNP has achieved the level of provider status,
      but only after successfully overcoming many practice restrictions and restraints
      over the decades. This article chronicles the history of the NNP and recounts the
      external and internal elements that contributed to the development of this
      profession.

PMID- 12240458
TI  - Chicagoland remembers....
AB  - A walk down memory lane is provided from the perspective of Chicagoland nurses
      who have each provided neonatal care for 20 years or greater. Sixteen nurses were
      interviewed, representing at least 11 different units in the area. Combined, over
      390 years of neonatal care have been provided by these nurses. An oral history
      was obtained by asking each the same three questions: What has changed in the
      past 20 years in neonatal nursing? What are your fondest memories of neonatal
      nursing in the past 20 years? What drives your "passion for little people"? This
      special group of nurses will warm your heart with their responses. They are a
      reminder of how much neonatal nursing has changed, but also how the "passion for
      little people" remains the same. On this special anniversary, nurses in many
      units, not only in Chicago, will be able to reflect with similar stories.

PMID- 12240459
TI  - Almost 20 years after a traumatic birth experience: "Joshua is doing just fine".
AB  - This personal account is about a labor and delivery experience that brought
      together two women--the author, an obstetric nurse, and Mrs. Hamilton,* the
      patient she cared for. This uneventful labor ended with the rapid delivery of
      Mrs. Hamilton's second son, who experienced a nuchal cord injury. This narrative
      describes selected aspects of her labor and delivery experience as well as short-
      and long-term outcomes for her newborn son. The unique nurse-patient relationship
      with its focus on caring and support is emphasized, in an attempt to illustrate
      the value and power of nursing by sharing one's own experiences of nursing
      practice.

PMID- 12240460
TI  - Knowledge translation and evidence-based perinatal/neonatal health care.
AB  - Knowledge translation is the process of bridging the gap between the overwhelming
      amount of research data/information/evidence and its critical appraisal,
      synthesis, dissemination, and application as knowledge by influential role
      models. Knowledge translation includes ongoing surveillance of the results of the
      implementation of new knowledge. By conducting research that is driven by
      relevant, well-defined questions and by using the most powerful study designs
      available, researchers generate valid new information that can later be
      translated into knowledge and applied in the clinical setting. Systematic reviews
      of the literature serve as good examples of knowledge management, when defined as
      "making proper use of the sum of what is known." Such reviews may identify that
      an intervention is effective without any harmful side effects, that it is
      noneffective, or that further research is warranted. Consumers of
      perinatal/neonatal health care or their ombudsmen should be encouraged to take
      part in setting the agenda and defining important outcomes for such research.

PMID- 12240461
TI  - The literature of neonatal nursing: stories from the turning points column.
AB  - The stories of neonatal care are a rich source of information, going beyond the
      typical clinical article to convey the meaning of nursing in this special
      environment. During its run, the Turning Points column in Neonatal Network gave
      nurses, doctors, and family members affected by the NICU an outlet to share their
      stories with others. The brief overview of the columns' contents provided in this
      article displays the wide variety of patient cases, workplace issues, and family
      situations encountered by neonatal nurses.

PMID- 12240462
TI  - Looking forward, looking back.

PMID- 12240465
TI  - [Emotional farewell and a greater number of presentations by members].

PMID- 12240464
TI  - [A passionate career].

PMID- 12240466
TI  - [Work methodology. Taking control of time].

PMID- 12240467
TI  - [Animals in the nursing home. The cat Leo and the goat Schnaggli as mood
      brighteners].

PMID- 12240468
TI  - [On the wrong side!].

PMID- 12240469
TI  - [New median in nursing education].

PMID- 12240470
TI  - ["I am only a nurse"].

PMID- 12240471
TI  - [Open eyes on nursing responsibility].

PMID- 12240472
TI  - [Health promotion. Hospital institutes a new state of hope].

PMID- 12240473
TI  - [Women power and nurse power].

PMID- 12240474
TI  - [The Holland model. "Problem-based learning" and "skills lab"].

PMID- 12240475
TI  - [Problem-based learning. In Switzerland, the preferred method].

PMID- 12240476
TI  - [Ethics reflection. From an egocentric focus to an ecologic focus].

PMID- 12240477
TI  - [An end to silence].

PMID- 12240481
TI  - Implantable defibrillator malfunctions should not be overlooked.

PMID- 12240482
TI  - Yoga may offer benefits to patients with cancer.

PMID- 12240483
TI  - Advertisement does not demonstrate safe practice.

PMID- 12240484
TI  - Cutaneous metastatic breast cancer.
AB  - Breast cancer is the most commonly diagnosed cancer in women and the second
      leading cause of cancer deaths among women in the United States. Many women
      diagnosed with breast cancer will achieve a cure with surgery followed by
      adjuvant chemotherapy, hormonal therapy, or radiation therapy; however, some
      breast cancer survivors will develop locally recurrent disease. Skin metastases
      are one of the most distressing presentations of locally recurrent breast cancer.
      The purpose of this article is to increase oncology nurses' understanding of the
      pathophysiology of cutaneous metastases, facilitate recognition of the various
      presentations of cutaneous metastatic breast cancer, discuss management of both
      the underlying disease process and skin lesions, and identify issues of
      psychosocial support for patients and families throughout the continuum of
      illness.

PMID- 12240486
TI  - Developing a protocol for obtaining blood cultures from central venous catheters
      and peripheral sites.
AB  - Blood cultures frequently are obtained from patients with cancer who are
      suspected to have infection. A review of the literature revealed that consistent
      clinical guidelines or standards for obtaining blood cultures from patients with
      cancer do not exist. The published literature varies greatly with respect to site
      selection (peripheral or central), frequency, and timing. In addition, a survey
      at the researchers' institution revealed that blood culture orders were written
      and interpreted in various ways. After a multidisciplinary discussion, a review
      of the literature, and receiving expert advice, an institutional protocol for
      obtaining blood cultures from patients with cancer was developed. The protocol
      specifies between peripheral and central line sampling and establishes timing,
      frequency, and other guidelines so nurses can perform consistent and evidence
      based blood culture sampling. Use of the protocol has improved patient care and
      helped standardize the practice of obtaining blood cultures.

PMID- 12240485
TI  - Epoetin alfa: current and future indications and nursing implications.
AB  - Cancer-related anemia commonly is associated with fatigue and decreased quality
      of life (QOL). Treatment to achieve optimal hemoglobin levels in patients
      receiving chemotherapy can alleviate common symptoms of anemia and may allow
      patients to have more meaningful survival time while on chemotherapy. New studies
      have suggested that epoetin alfa (Procrit, Ortho Biotech Products, LP, Raritan,
      NJ) can be administered safely and effectively once a week in patients with
      anemia other than those patients with cancer receiving concomitant chemotherapy.
      Preclinical studies and pilot clinical studies also have suggested a new
      application for epoetin alfa in improving cognitive function. Oncology nurses
      skilled at anticipating, assessing, and managing anemia and its symptoms can be
      instrumental in improving the QOL of patients with cancer. They should be aware
      of clinical trials that have suggested advantages of improved dosing schedules
      and new applications for epoetin alfa.

PMID- 12240487
TI  - Nursing assessment of sexual function following permanent prostate brachytherapy
      for patients with early-stage prostate cancer.
AB  - Assessment of sexual function following potentially curative local treatment for
      carcinoma of the prostate gland has resulted in wide ranges of potency
      preservation rates, which may be because of differences in the evaluated patient
      populations, mode of data collection, and length of patient follow-up. Quality-of
      life data are most reliable when obtained by patient-administered and validated
      quality-of-life instruments. In the Schiffler Cancer Center's prostate
      brachytherapy unit, healthcare professionals utilize the specific erectile
      questions of the International Index of Erectile Function to ascertain pre- and
      post-treatment erectile function. Documentation of sexual function following all
      local treatments, including prostate brachytherapy, may help to clarify the
      etiology of treatment-induced erectile dysfunction (ED), improve treatment for
      ED, and, ultimately, improve quality-of-life outcomes. Fortunately, the majority
      of patients with brachytherapy-induced ED respond favorably to sildenafil
      citrate.

PMID- 12240488
TI  - Enteral feedings with comfort and safety.
AB  - Patients who are unable to eat by mouth can be fed in a manner that maintains the
      structural and functional integrity of the gastrointestinal tract. The
      appropriate choice of type of feeding tube to use is based on the reasons
      patients need to be tube fed and the expected duration of need for the tube. Once
      the tubes are placed, verification of placement is critical for safe use.
      Patients, family caregivers, and staff must assess for potential complications.
      Misplacement is the most common problem of feeding tubes. Life-threatening
      complications can include "refeed syndrome" and "buried bumper syndrome."
      Additional threats include contaminated tube feeding and inappropriate medication
      administration. Feeding too rapidly into the small intestine can cause necrosis
      of the small bowel. To maintain patient comfort, site care is critical.
      Nasogastric tubes can cause permanent deformity of the nares. Gastric drainage on
      the skin can cause painful excoriation that is difficult to manage. With careful
      monitoring of tube feedings, positive nutritional status can be achieved. A
      positive nutritional status assists in promoting health and immune function.

PMID- 12240490
TI  - Nutrition in critical care.
AB  - Many hospitalized patients with cancer are malnourished. Some become critically
      ill and experience delayed wound healing, loss of muscle strength, and reduced
      infection fighting ability as a consequence of the loss of nutritional reserves.
      Complications of critical illness may cause interruption in normal
      gastrointestinal function and result in shock, sepsis, hypochlorhydria, systemic
      inflammatory response syndrome, and other disorders. As a result, critically ill
      patients may require nutritional support.

PMID- 12240489
TI  - Waldenstrom's macroglobulinemia.
AB  - Waldenstrom's macroglobulinemia (WM) is a rare monoclonal gammopathy. Its
      clinical signs and symptoms include fatigue, weakness, hepatomegaly,
      splenomegaly, lymphadenopathy, and neuropathies. Patients with WM have a
      circulating tumor marker, the monoclonal immunoglobulin M protein. High levels of
      this protein can produce hyperviscosity syndrome, which often is characterized by
      bleeding from the mucous membranes of the nose and mouth. Asymptomatic patients
      with WM usually are not treated. Treatment of symptomatic patients and patients
      with relapsed WM may include alkylating agents, particularly chlorambucil; purine
      nucleoside analogs, such as fludarabine and cladribine; and, most recently, the
      use of rituximab. With knowledge about this unusual disease, oncology nurses can
      provide better care and education for patients with WM.

PMID- 12240491
TI  - Handling and disposal of monoclonal antibodies.

PMID- 12240493
TI  - Labyrinths: a pathway to reflection and contemplation.

PMID- 12240492
TI  - Administering meperidine to patients with cancer.

PMID- 12240494
TI  - Ask an expert: constructing labyrinths for patients with cancer.

PMID- 12240495
TI  - Gemtuzumab ozogamicin.

PMID- 12240496
TI  - Malignant cutaneous wounds.
AB  - Very little literature is available about malignant cutaneous fungating wounds,
      and most of the research has been conducted in England. Although only a small
      number of patients with cancer develop the traumatic and devastating complication
      of a malignant cutaneous wound, it can be a very distressing occurrence. These
      patients usually are in the last few months of their lives, and the presence of a
      wound may be a constant reminder of their disease (Naylor, 2002). In addition,
      patients may need to cope with bleeding, exudates, odor, or infection. Caring for
      these patients may be challenging but it can be rewarding if the patients are
      able to maintain or improve their quality of life.

PMID- 12240497
TI  - Violaceous skin reaction of the hand.

PMID- 12240498
TI  - Computerization: are we losing the human side?

PMID- 12240499
TI  - The effects of aromatherapy on pruritus in patients undergoing hemodialysis.
AB  - This study was designed to investigate the effects of aromatherapy on pruritus in
      patients with chronic renal failure undergoing hemodialysis. The participants
      were 29 adult patients living in Seoul, Korea. Thirteen patients were assigned to
      the experimental group and received the aromatherapy massage on the arm 3 times a
      week for 4 weeks. Pruritus score, skin pH, stratum corneum hydration, and
      pruritus-related biochemical markers were measured before and after the
      treatment. The results showed that pruritus score was significantly decreased
      after aromatherapy. Skin pH showed no significant changes in either group while
      stratum corneum hydration increased significantly in the experimental group after
      aromatherapy. The results support the use aromatherapy as a useful and effective
      method of managing pruritus in patients undergoing hemodialysis.

PMID- 12240500
TI  - Overview of treatments for acne.
AB  - Acne vulgaris is a chronic inflammatory condition of the pilosebaceous units.
      Antibiotics are widely used in acne therapy and can be administrated topically or
      systemically. The main negative effect of antibiotic treatment is bacterial
      resistance to antibiotics.

PMID- 12240501
TI  - What's your assessment? Lichen simplex chronicus.

PMID- 12240502
TI  - Morbid obesity: a nursing care challenge.
AB  - Obesity is one of the nation's most serious health problems. When individuals are
      overweight, they are at risk for disease, medical complications, and death.
      Patients are considered morbidly obese or bariatric when their weight far exceeds
      recommended guidelines. Excess weight in these individuals increases morbidity
      and mortality, and causes numerous care challenges. Nurses caring for bariatric
      clients should recognize the need to use specialized assessment and management
      strategies to prevent poor patient outcomes.

PMID- 12240503
TI  - Wound healing: translating theory into clinical practice.1995.

PMID- 12240504
TI  - Wound assessment and evaluation: wound documentation guidelines.

PMID- 12240506
TI  - Leading the leaders: the challenge of leading an empowered organization.
AB  - Professionals expect to be treated as peers and equals to the leader/manager.
      Nurse leaders must concentrate on leading the empowered workforce in new and
      different ways. The rewards make the concept of "herding cats" challenging and
      worthwhile.

PMID- 12240505
TI  - Imiquimod (Aldara): modifying the immune response.
AB  - Imiquimod 5% cream represents a new class of topically applied immune response
      modifiers that are capable of enhancing immune function. It stimulates both the
      innate arm of the immune system as well as cell-mediated immunity. It is
      currently indicated for treating genital human papilloma virus infection.
      However, because of its action on the immune system it shows promise for wide
      applicability in treating other viral skin infections as well as neoplastic and
      immune-mediated diseases of the skin.

PMID- 12240508
TI  - When disaster strikes: lessons learned from Hurricane Allison.

PMID- 12240507
TI  - Extramammary Paget's disease.

PMID- 12240509
TI  - Most Americans ignore changes in the appearance of their nails, survey shows.

PMID- 12240511
TI  - Issues related to prenatal diagnosis of congenital heart disease.
AB  - Enhanced technology and professional expertise are making the diagnosis of
      congenital heart disease possible with increasing frequency during the prenatal
      period. This article describes the process of prenatal diagnosis of congenital
      heart disease and the many personal issues families face when they receive news
      of this condition. Ethical and legal considerations of prenatal diagnosis are
      reviewed. Brief vignettes describe what families experience when they receive the
      diagnosis. The role of the nurse in educating parents, assisting them in sorting
      out options for treatment, and providing ongoing care and support is discussed,
      and implications for nurses in obstetric, neonatal, and pediatric settings are
      reviewed. Finally, the need for further research on this topic is explored.

PMID- 12240510
TI  - Validation of the Pain Assessment in Neonates (PAIN) scale with the Neonatal
      Infant Pain Scale (NIPS).
AB  - PURPOSE: To establish the validity and clinical usefulness of a modified pain
      assessment scale, the Pain Assessment in Neonates (PAIN) scale. DESIGN:
      Correlational design to compare scores obtained on the PAIN with scores obtained
      on the Neonatal Infant Pain Scale (NIPS). SAMPLE: A convenience sample of 196
      neonates from an NICU and a step-down unit with gestational ages of 26 to 47
      weeks. METHOD: Bedside nurses observed the neonates for two minutes and then
      scored their responses on both scales. The scales were scored sequentially and in
      a randomized order. MAIN OUTCOME VARIABLE: Correlation of individual item scores
      and total scores on the PAIN and the NIPS. RESULTS: The scores for individual
      items on the PAIN were significantly associated with scores obtained on the NIPS.
      Overall correlation between the scales was 0.93. These associations suggest that
      the PAIN is a valid scale for assessment of neonatal pain.

PMID- 12240512
TI  - Cultural differences and parental responses to the preterm infant at risk:
      strategies for supporting families.
AB  - Parenting a preterm infant at risk for developmental disabilities can be a
      profoundly stressful experience. For parents from minority cultures, language
      barriers and cultural differences can increase feelings of uncertainty and
      inability to cope. Research suggests that cultural differences influence not only
      parents' emotional responses to and perceptions of disability, but also their
      utilization of services and their interaction with health professionals. The
      Neonatal Intensive Care Unit of Mount Sinai Hospital (MSH), Toronto, provides
      care to a culturally diverse community, and approximately 45 percent of patients
      receiving care represent minority ethnic groups. Although efforts to provide
      culturally sensitive care have been made, they have tended to be isolated
      initiatives lacking consistency and coordination. This article describes the
      initiation and development of a multicultural program at MSH to support families
      of infants at risk for developmental disabilities. This article provides valuable
      guidance to other neonatal units that are attempting to support parents from
      diverse cultural groups.

PMID- 12240513
TI  - The "geriatric" NICU patient.

PMID- 12240514
TI  - Neonatal herpes simplex: pulmonary and intracranial findings.

PMID- 12240515
TI  - Congenital cutaneous candidiasis: a case presentation.
AB  - When an infant presents in the delivery room with macular and papular skin
      lesions covering the trunk, extremities, and/or skin folds, the neonatal nurse
      practitioner covering deliveries must be aware of possible skin lesion
      differential diagnoses. Among these is congenital cutaneous candidiasis, a rare,
      usually benign skin infection. If this condition is recognized early, unnecessary
      testing and treatment of newborns who present with these symptoms might be
      avoided.

PMID- 12240516
TI  - Written and computerized care plans. Organizational processes and effect on
      patient outcomes.
AB  - The purpose of this study was to determine how use of a standardized nomenclature
      for nursing diagnosis and intervention statements on the computerized nursing
      care plan in a long-term care (LTC) facility would affect patient outcomes, as
      well as organizational processes and outcomes. An experimental design was used to
      compare the effects of two methods of documentation: Computer care plan and paper
      care plan. Twenty participants (10 in each group) were randomly assigned to
      either group. No statistically significant differences were found by group for
      demographic data. Repeated measures ANOVA was computed for each of the study
      variables with type of care plan, written or computerized, as the independent
      variable. There were no statistically significant differences between
      participants, group (care plan), within subjects (across time), or interaction
      (group and time) effects for the dependent variables: Level of care, activities
      of daily living, perception of pain, cognitive abilities, number of medications,
      number of bowel medications, number of constipation episodes, weight, percent of
      meals eaten, and incidence of alteration in skin integrity. There were
      significantly more nursing interventions and activities on the computerized care
      plan, although this care plan took longer to develop at each of the three time
      periods. Results from this study suggest that use of a computerized plan of care
      increases the number of documented nursing activities and interventions, but
      further research is warranted to determine if this potential advantage can be
      translated into improved patient and organizational outcomes in the long-term
      care setting.

PMID- 12240517
TI  - The experience of hospitalized elderly patients.
AB  - Little is known about the subjective experience of older adults during
      hospitalization. The purpose of this study was to identify and describe the
      hospitalization process as perceived by older adults. This qualitative study
      explored hospitalization as perceived by eight White, middle-class, elderly
      patients in one large, western, acute care hospital. Thirty initial codes were
      identified from qualitative interviews, participant observation, and medical
      records. Using constant comparative analyses, these initial codes were
      reevaluated and further condensed into seven categories. The categories comprise
      positive and negative perceptions, including numerous difficulties experienced by
      these hospitalized older patients. Findings of this study are compared to
      findings existing in the current literature. These findings may be useful in
      understanding the problems related to the hospitalization experience, identifying
      interventions that could minimize stressors, and facilitating this experience for
      older patients.

PMID- 12240519
TI  - A different view of quality care.

PMID- 12240518
TI  - Knowledge and self-efficacy of community health nurses concerning interactions of
      prescription medicines with over-the-counter agents and alcohol.
AB  - Knowledge and self-efficacy concerning interactions of prescription medications
      with over-the-counter (OTC) agents were assessed in community health nurses.
      Three convenience samples of community nurses were recruited to complete the
      instruments. The first was a sample of 20 experienced nurses working for a local
      visiting nurse agency (VNARNs). The second was a sample of 20 bachelor of science
      in nursing (BSN) students (graduate nurses [GNs]) completing their final nursing
      rotation with the VNARNs. The third was a sample of 31 nurses enrolled in a
      graduate program training nurses for advanced practice (APRNs). There were no
      significant differences in overall mean self-efficacy scores among the groups of
      community health nurses. The mean scores indicated moderate self-efficacy about
      prescription-OTC interactions. Post-hoc analyses determined VNARNs had
      significantly greater knowledge scores than APRNs. Overall mean self-efficacy was
      not correlated with mean knowledge scores. Inspection of the knowledge item
      responses revealed nine general misconceptions about OTC medications held by many
      community nurses in the sample. The data can guide the development of continuing
      education programs about prescription-OTC interactions aimed at community health
      nurses.

PMID- 12240520
TI  - Advance directives. Why community-based older adults do not discuss their wishes.
AB  - Health care providers and family members need direction when making health
      decisions for individuals who are unable. Advance directives allow individuals to
      maintain control of health care decisions. Despite that the majority of the
      population supports the right to express wishes related to end-of-life care, few
      implement advance directives. The purpose of this study was to determine reasons
      why community-based older adults discuss, do not discuss, or formalize advance
      directives. A convenience sample of 55 adults age 50 or older, participated in
      the study by answering a 31-question self-report questionnaire. Death or serious
      illness of a loved one was the most influential factor prompting formulation of
      an advance directive. However, the majority of the population has not expressed
      their health care wishes in the form of advance directives. Therefore, continuing
      to educate and encourage discussion of advance directives is imperative.

PMID- 12240521
TI  - Using family-style meals to increase participation and communication in persons
      with dementia.
AB  - Although researchers stress the importance of encouraging independent behavior in
      persons with dementia, institutional practices often foster dependence. This
      study took place in a six-resident locked dementia care unit that followed the
      common institutional practice of serving meals on prepared plates. The purpose of
      this study was to examine if changing the mode of meal delivery to "family
      style," where residents were presented with serving bowls and empty plates, would
      increase resident communication and participation in mealtime tasks. An ABAB'
      reversal design revealed very low rates of appropriate communication (5% of
      intervals) and mealtime participation (10% of tasks) during baseline, when
      residents received prepared plates (A). Communication and participation doubled
      when family-style meal delivery was introduced (B) and dropped back to baseline
      levels when it was withdrawn (A). Because the levels of communication and
      participation during family-style meals were still low, the nursing assistant was
      provided with instruction on prompting and praising appropriate mealtime
      behaviors (B'). After instruction was provided and family-style meals were
      reintroduced, resident participation rose to 65% of tasks and appropriate
      communication increased to 18% of observations. This study suggests family-style
      meals may result in modest increases in mealtime participation and communication
      of residents with dementia, but staff training in prompting and praising may be
      necessary to see large changes in these behaviors.

PMID- 12240522
TI  - Resting and reactive blood pressure. Predictors of ambulatory blood pressure in
      older adults with hypertension.
AB  - The study examined whether reactive change scores from a short blood pressure
      (BP) reactivity protocol, resting BP, or resting pulse pressure (PP) would be
      predictors of 24-hour ambulatory BP and BP load in cardiac patients. The study
      used a single-group design, with both an experimental clinical component and an
      observational field component. Both components used repeated measurement methods.
      The study population consisted of 45 adult patients with a mean age of 64.6 +/-
      8.5 years who were diagnosed with cardiac disease in a cardiac rehabilitation
      program and who were taking anti-hypertensive medication. Blood pressure
      reactivity was operationalized with a speech protocol. During the speech
      protocol, BP was measured with an automatic device (Dinamap) while patients
      talked about their health and about their usual day. Twenty-four-hour ambulatory
      BP measurement followed the speech protocol. Resting systolic BP and resting PP
      were significant predictors of 24-hour ambulatory systolic BP, and resting
      systolic BP was a significant predictor of systolic BP load. No predictors were
      significant of 24-hour diastolic BP or diastolic BP load. Initial resting BP and
      PP may be used in clinical settings to assess hypertension management. Future
      studies are necessary to confirm the ability of resting BP to predict ambulatory
      BP and BP load in older adults who are medicated and hypertensive.

PMID- 12240523
TI  - Odontoblast phosphate and calcium transport in dentinogenesis.
AB  - It has been suggested that odontoblasts are instrumental in translocating Ca2+
      and inorganic phosphate (Pi) ions during the mineralization of dentin. The aim of
      this thesis was, therefore, to study the expression of components of the
      transcellular ion transport system, Na+/Ca2+ exchangers and Na(+)-Pi
      contransporters, in odontoblastic and osteoblastic cells. Their activity was
      assayed in osteoblast-like cells and in the recently developed MRPC-1 odontoblast
      like cell line. To assess the relationship between ion transport and
      mineralization, Ca2+ and Pi uptake activities were determined in mineralizing
      cultures of MRPC-1 cells. Osteoblastic and odontoblastic cells showed an
      identical expression pattern of Na+/Ca2+ exchanger splice-variants, NCX1.3,
      NCX1.7 and NCX1.10, derived from the NCX1 gene, while NCX2 was not expressed. The
      cells showed a high sodium-dependent calcium extrusion activity. Regarding Na(+)
      Pi cotransporter expression, Glvr-1, Ram-1 and the two high capacity
      cotransporters Npt-2a and Npt-2b were found to be expressed in odontoblasts and
      MRPC-1 cells. Osteoblast-like cells differed from this in expressing the Npt-1
      but not the Ram-1 gene but were otherwise identical to the odontoblastic cells.
      Odontoblast-like cells exhibited almost twice the sodium-dependent Pi uptake
      activity of osteoblast-like cells. The presence of NaPi-2a and NaPi-2b, gene
      products of Npt-2a and Npt-2b, was verified in vivo by immunohistochemistry on
      mouse teeth. Both cotransporters could be detected in fully differentiated,
      polarized odontoblasts but not in preodontoblasts prior to dentin formation. Both
      cotransporters were detected in adjacent bone and in ameloblasts. Studying ion
      uptake in mineralizing MRPC-1 cultures, large changes were detected concomitant
      with the onset of mineral formation, when phosphate uptake increased by 400%
      while calcium uptake started to decline. The increase in Pi uptake was found to
      be due to activation of the NaPi-2a cotransporter. MRPC-1 cells expressed an
      odontoblast-like phenotype already at the onset of culture, but in order to form
      mineral a differentiation involving their ion transporters seems necessary.
      Calculating the theoretical rate of ion transport needed for dentin formation and
      comparing with data from the studies in this thesis showed that transcellular ion
      transport is both possible and sufficient to meet the phosphate and calcium
      demands of dentinogenesis.

PMID- 12240524
TI  - An ethicist's commentary on the mishandling of an injured animal by a raptor
      rehabilitation facility.

PMID- 12240525
TI  - Animal welfare and the harp seal hunt in Atlantic Canada.
AB  - Much attention has been given over the years to animal welfare issues surrounding
      the seal hunt in Atlantic Canada. However, very little information is available
      on this subject in the scientific literature. This article reports the results of
      observations made by representatives of the Canadian Veterinary Medical
      Association at the hunt in recent years and compares them with observations made
      by members of the International Fund for Animal Welfare. The conclusion is that
      the large majority of seals taken during this hunt (at best, 98% in work reported
      here) are killed in an acceptably humane manner. However, the small proportion of
      animals that are not killed effectively justifies continued attention to this
      hunt on the part of the veterinary profession.

PMID- 12240526
TI  - A trap, neuter, and release program for feral cats on Prince Edward Island.
AB  - A new program to address the feral cat population on Prince Edward Island was
      undertaken during the spring and summer of 2001. Feral cats from specific
      geographic areas were trapped, sedated, and tested for feline leukemia virus and
      feline immunodeficiency virus. Healthy cats were neutered, dewermed, vaccinated,
      tattooed, and released to their area of origin. A total of 185 cats and kittens
      were trapped and tested during a 14-week period; 158 cats and kittens as young as
      6 weeks of age were neutered and released. Twenty-three adult cats were positive
      for feline leukemia virus, feline immunodeficiency virus, or both, and were
      euthanized.

PMID- 12240527
TI  - A comparison of 2 different suture patterns for skin closure of canine
      ovariohysterectomy.
AB  - The purpose of this study was to compare postoperative wound healing in canine
      ovariohysterectomy following the use of an absorbable monofilament poliglecaprone
      25 suture in 2 different skin closure techniques, the buried continuous
      subcuticular (BCS) suture pattern and the simple interrupted (SI) suture pattern.
      These 2 skin closure techniques were evaluated against a nonabsorbable
      polypropylene monofilament suture in an SI pattern. Wounds were assessed by using
      a semiquantitative scoring system at 18 to 24 hours and 10 to 14 days,
      postoperatively. Results indicated that the BCS closure using poliglecaprone 25
      demonstrated a higher rate of tissue reactivity initially (18-24 hours
      postoperatively), as compared with the SI closure using either suture material.
      By 10 to 14 days postoperatively, poliglecaprone 25 used in a BCS closure was
      associated with significantly lower wound scores than was the same material used
      in an SI closure. It was concluded that the BCS closure may effect a better
      cosmetic appearance to the skin closure in a canine ovariohysterectomy at the
      time of the recheck appointment. Furthermore, by obviating the need for suture
      removal, use of the BCS pattern may eliminate the requirement for this return
      appointment.

PMID- 12240528
TI  - Chronic idiopathic pulmonary fibrosis in a West Highland white terrier.
AB  - A 9-year-old, spayed, female West Highland white terrier was presented with a
      chronic cough, lethargy, and exercise intolerance. Thoracic radiographic findings
      were consistent with a marked interstitial lung pattern. Idiopathic pulmonary
      fibrosis, a disease anecdotally linked to this breed, was diagnosed on postmortem
      examination.

PMID- 12240529
TI  - Rhodococcus equi pleuropneumonia in an adult horse.
AB  - A 10-year-old warmblood gelding was evaluated for intermittent pyrexia, dullness,
      weight loss, and progressive respiratory disease. Multifocal necrotic pneumonia
      and pleuritis due to Rhodococcus equi infection was diagnosed. Case management is
      discussed, as well as factors that may have led to this rare cause of
      pleuropneumonia in an adult horse.

PMID- 12240530
TI  - Multicentric canine lymphoma in a 12-year-old keeshond: chemotherapy options.
AB  - A 12-year-old, spayed female keeshond presenting with lethargy, anorexia, weight
      loss, and vomiting was diagnosed with multicentric lymphoma. Lymphoma usually
      responds well to multiagent chemotherapy. Efficacy, cost, toxicity, and duration
      of treatment determine a treatment protocol. Outcomes are compared on the basis
      of remission, survival time, and treatment-related toxicity.

PMID- 12240531
TI  - An endodermal cyst: the result of a congenital intestinal malformation.
AB  - A midline exploratory laparotomy on a 1-year-old, neutered male, West Highland
      terrier with a history of lethargy, anorexia, and intermittent vomiting revealed
      a cranial abdominal cyst. The lining of the excised cyst was histologically
      identical with that of the small intestine and may have represented an uncommon
      intestinal malformation.

PMID- 12240532
TI  - Foal with Overo lethal white syndrome born to a registered quarter horse mare.
AB  - A 16-hour-old white foal, born to a registered quarter horse mare, was examined
      for signs of colic. The foal had Overo lethal white syndrome, which causes
      ileocolonic agangliosis. This was confirmed by DNA testing. Since there is no
      treatment for Overo lethal white syndrome, the foal was euthanized.

PMID- 12240533
TI  - Effect of monensin on survival and growth of Escherichia coli O 157:H7 in vitro.

PMID- 12240534
TI  - Dissecting aortic aneurysm in a cat.

PMID- 12240535
TI  - The eradication of glanders in Canada.

PMID- 12240536
TI  - Diagnostic ophthalmology. Acute prechiasmal blindness due to sudden acquired
      retinal degeneration syndrome.

PMID- 12240537
TI  - Transfer of facility clients to inpatient psychiatry: eight criteria to consider.
AB  - The transfer of residential clients with mental retardation to inpatient
      psychiatric care units (IPUs) presents several areas in which clinical and
      administrative incidents can occur. Incident review management can be applied as
      an effective administrative tool to improve the transfer of such clients by
      considering the needs of clients in the context of their caregivers and the goals
      of the IPU. This article introduces eight criteria to facilitate and evaluate the
      transfer of such clients and help reduce the rate of incidents.

PMID- 12240538
TI  - Mary Wakefield on health policy and national quality initiatives. Interview by
      Patti Klingel and Denise A. Kent.

PMID- 12240539
TI  - Directory of Internet documents for consumers on quality of care.
AB  - Healthcare professionals have an important role in helping patients and families
      understand the concept of healthcare quality and gain access to available
      information on quality care. Information about quality of healthcare is available
      from many reputable sources on the Internet. A resource directory that leads
      consumers to these sites would be a useful tool for patient education. This
      article describes (a) the process of retrieving and evaluating Web site documents
      on quality care, using criteria developed by the Health Information Technology
      Institute, and (b) the method of organizing them into a logical structure using
      Mind Map software. The 32 documents that make up the directory are included in a
      table under subheadings developed with concept mapping.

PMID- 12240540
TI  - Reducing length of stay through rapid clinical redesign.
AB  - The SETON Healthcare Network in Austin, TX, significantly reduced length of stay
      in six diagnostic-related groupings by successfully combining medical management
      activities and cost-savings targets. This article describes how organizational
      infrastructure, leadership, clinical redesign, and risk-adjusted data were
      combined to drive performance improvements and create enthusiasm for change.

PMID- 12240541
TI  - Barriers to successful implementation of a clinical pathway for CHF.
AB  - Clinical pathways represent a strategy for responding to the current healthcare
      environment with a focus on managing care, reducing costs, increasing patient
      satisfaction, and improving quality. However, many healthcare organizations have
      found that implementing clinical pathways is not entirely successful even when
      they are based on sound evidence. The purpose of this case study was to describe
      and explain factors related to the success or failure of implementing a clinical
      pathway for congestive heart failure (CHF) patients in a 300-bed community
      hospital. The key factors involved in the nonadoption of the CHF pathway were
      inconsistencies in procedures and the work group culture.

PMID- 12240542
TI  - Ten keys to successful NCQA accreditation: a health plan perspective.

PMID- 12240543
TI  - Trends in adverse events in hospitalized patients.
AB  - The Institute of Medicine reported unacceptably high rates of medical error but
      did not identify whether this is a growing or a stabilized problem. This study
      used longitudinal data from all acute care hospitals in Pennsylvania to track
      rates of acuity-adjusted iatrogenic atelectasis, cardiac complications,
      complications in general, decubitus ulcers, gangrenous ulcers, falls, hemorrhage,
      mortality, penumonia, post-procedural infections, treatment complications, and
      urinary tract infections, from 1994 to 1997. More than one-half of these adverse
      events increased during this time. It is important to identify the causes and
      correct trends in hospital systems that may produce an increase in preventable
      adverse events.

PMID- 12240544
TI  - AONE call to action: it's about people.

PMID- 12240545
TI  - The Press, Ganey Annual National Client Conference: solid foundations, lasting
      success.

PMID- 12240546
TI  - Immunohistochemically detected p53 mutations in epithelial tumors and results of
      treatment with chemotherapy and radiotherapy. A treatment-specific overview of
      the clinical data.
AB  - BACKGROUND: The aim was to ascertain whether many hundreds of clinical reports
      over the last decade are consistent with the prediction of a poorer outcome in
      cancer patients with p53 abnormalities treated with cytotoxic drugs and
      radiation. MATERIAL AND METHOD: There are 301 studies on the influence of p53
      overexpression published through summer 2000, in which chemotherapy or
      radiotherapy was used alone or in combination with surgery. From 45 reports
      meeting stringent selection rules, comparison groups are identified in whom the
      same measure of outcome was reported for the same treatment applied to the same
      tumor, with results corrected for important prognostic factors. Metaanalysis
      techniques are then applied to the comparison groups. Attention was limited to
      reports using immunohistochemical techniques, to form comparison groups of
      sufficient size. RESULTS: Four comparison groups were identified by treatment and
      endpoint: 1) Stage I-III breast cancer (surgery and chemotherapy, disease-free
      survival, seven studies); 2) stage I-III breast cancer (surgery and chemotherapy,
      overall survival, six studies); 3) stage II-IV head and neck cancer (radiotherapy
      and chemotherapy, overall survival, five studies); 4) FIGO I-IV ovarian cancer
      (surgery and chemotherapy, overall survival, six studies). In the breast (disease
      free survival) and ovarian (overall survival) comparison groups, the hazard ratio
      for a deleterious effect of p53 overexpression was significant or marginally
      significant, depending on assumed ranges for unreported hazard ratios in non
      significant studies. CONCLUSIONS: Despite the many caveats related to
      metaanalysis applied to retrospective data, high variability of
      immunohistochemical technique, etc., a nearly significant negative effect of p53
      overexpression on outcome of treatment with cytotoxic drugs and radiation emerges
      in the few studies where heterogeneity can be sufficiently reduced or accounted
      for.

PMID- 12240547
TI  - The value of PSA measurements at 30 Gy, 50 Gy and 60 Gy for dose limitation in
      patients with radiotherapy for PSA increase after radical prostatectomy.
AB  - BACKGROUND: Radiation therapy is a treatment option for patients with rising PSA
      after radical prostatectomy without histological evidence of local relapse and no
      signs of distant metastases. Prior to radiotherapy there is no certainty whether
      a patient is going to respond to the treatment or not. When total doses of more
      than 60 Gy are given there is an exponential rise in treatment-related late
      toxicity. Therefore those patients in whom radiotherapy later appears to be
      ineffective may benefit from a dose restriction to 50-60 Gy. The aim of this
      study was to examine the prognostic value of PSA levels evaluated during
      radiotherapy. PATIENTS AND METHODS: 41 patients with rising PSA level following
      prostatectomy received radiotherapy to the prostatic bed and were treated up to a
      median dose of 66.6 Gy. We evaluated serum PSA levels during radiotherapy at 30
      Gy, 50 Gy, and 60 Gy and compared them to the pre-radiotherapy PSA level and the
      outcome of radiotherapy. RESULTS: After radiotherapy, 31 patients (76%) had
      either undetectable (n = 15), or decreasing but still detectable PSA levels (n =
      16) and ten patients (24%) had rising PSA levels and did not respond. PSA
      evaluation at 30 Gy showed that 26% (8/31) of those patients who would respond to
      radiotherapy still had a rising PSA when compared to pretreatment PSA. At 50 Gy
      and 60 Gy 93% (27/29) of these patients had decreasing PSA levels. In contrast,
      75% (6/8) and 88% (7/8) of those patients in whom radiotherapy was not effective
      had rising PSA levels at 50 Gy and 60 Gy (p < 0.05). CONCLUSIONS: PSA
      measurements at 30 Gy, 50 Gy and 60 Gy for radiotherapy of PSA increase following
      radical prostatectomy without histologically proven local recurrence gives
      valuable information about the later tumor response. Therefore it possibly gives
      the opportunity to finish radiotherapy between 50 and 60 Gy, as almost all
      patients with continued PSA increase at 60 Gy do not stand to profit from
      radiotherapy. In these patients dose limitation would significantly decrease the
      risk of late side effects, especially for the bladder and the rectum. PSA
      evaluations at 30 Gy and 50 Gy or 60 Gy are recommendable.

PMID- 12240548
TI  - High survivin expression is associated with reduced apoptosis in rectal cancer
      and may predict disease-free survival after preoperative radiochemotherapy and
      surgical resection.
AB  - BACKGROUND: Spontaneous apoptosis has been shown to predict tumor response to
      preoperative radiochemotherapy in rectal cancer. It remains to be elucidated,
      however, which genetic profile determines whether a tumor is more or less prone
      to apoptosis. Recently, a novel member of the inhibitor of apoptosis family,
      designated survivin, was identified. In the present study, we investigated the
      impact of survivin on tumor cell apoptosis and the risk to develop distant
      metastases or local failure after preoperative radiochemotherapy and surgical
      resection. PATIENTS AND METHODS: The expression of survivin, p53, bcl-2 and the
      apoptotic index was evaluated by immunohistochemistry on pretreatment biopsies of
      54 patients with locally advanced adenocarcinoma of the rectum. Survivin
      expression was correlated to clinical and histopathological markers, the levels
      of spontaneous apoptosis, p53 and bcl-2, as well as to disease-free survival, 5
      year rates of local failure and distant disease after preoperative
      radiochemotherapy and surgical resection. RESULTS: Survivin expression inversely
      correlated with the apoptotic index: High survivin expression was found in 56% of
      rectal carcinoma biopsies with a median apoptotic index of 1.22%. Conversely, low
      survivin expression in tumor cells was associated with a high median apoptotic
      index (2.29%, p = 0.0001). High survivin expression also segregated with bcl-2
      overexpression (65% bcl-2+ in tumors with high survivin expression as compared to
      35% bcl-2+ in tumors with low survivin expression), but the difference was not
      statistically significant (p = 0.1). Low survivin expression was significantly
      related to an increased disease-free survival rate (77% vs 18% at 5 years in
      tumors with high survivin expression, p = 0.02) and to a reduced risk for distant
      metastases (18% vs 78% at 5 years in tumors with high survivin expression, p =
      0.05) and local failure (6% vs 37% at 5 years in tumors with high survivin
      expression, p = 0.07). CONCLUSION: An inverse correlation between survivin
      expression and the level of spontaneous apoptosis in pretreatment biopsies
      suggests that survivin strongly inhibits tumor cell apoptosis in rectal cancer.
      Survivin expression may provide a novel predictive indicator for disease-free
      survival after preoperative radiochemotherapy and surgical resection in rectal
      cancer.

PMID- 12240549
TI  - Anemia and elevated systemic levels of vascular endothelial growth factor (VEGF).
AB  - BACKGROUND: Tissue hypoxia is a major stimulus for the up-regulation of vascular
      endothelial growth factor (VEGF). Anemia might theoretically impact on
      angiogenesis via impairment of tissue oxygenation. We have investigated this
      hypothesis in patients with solid cancers and benign diseases. PATIENTS AND
      METHODS: 49 patients with untreated locoregionally confined solid cancers of the
      head and neck, cervix, rectum and lung and 59 additional patients with non
      malignant diseases (36 normemic patients without serious diseases and 23 patients
      with renal anemia) were enrolled and the impact of anemia on plasma VEGF levels
      were determined. VEGF was measured with a commercially available sandwich enzyme
      immunoassay technique. RESULTS: Plasma levels of VEGF were 16.2 +/- 12.7 pg/ml in
      36 normemic patients without malignant disease, 49.2 +/- 34.5 pg/ml in 49
      patients with cancers (p < 0.001), and 89.9 +/- 67.8 pg/ml in 23 patients with
      renal anemia (p = 0.001). VEGF levels in cancer patients were significantly
      correlated with hemoglobin (hb) levels and platelet counts (each p = 0.001), but
      not with type of tumor, stage, histology or age. Patients with cancers had higher
      plasma levels of VEGF than patients with non-malignant diseases in case of hb >
      or = 12 g/dl (33.1 +/- 17.5 vs 16.6 +/- 13.0 pg/ml, p < 0.001) and in case of hb
      between 11.0 and 11.9 g/dl (56.1 +/- 26.4 vs 18.5 +/- 14.5 pg/ml, p = 0.038). In
      case of a hb < 11 g/dl, plasma VEGF levels were significantly elevated in
      patients with and without cancers (67.0 +/- 47.5 vs 88.9 +/- 68.8 pg/ml, n.s.).
      In a multivariate model, a significant association between low hb levels and
      increased plasma levels of VEGF was confirmed. In 16 patients with renal anemia,
      changes in hb under erythropoietin treatment were inversely correlated with
      changes in plasma VEGF levels with decreasing VEGF after increase in hb (p =
      0.01). CONCLUSIONS: Anemic patients have elevated levels of VEGF. The data
      suggest that anemia might impact on the progression of angiogenesis in malignant
      and benign diseases.

PMID- 12240550
TI  - Fractionated intraluminal HDR 192Ir brachytherapy as palliative treatment in
      patients with endobronchial metastases from non-bronchogenic primaries.
AB  - AIM: To evaluate the efficacy of iridium-192 high-dose rate (HDR) endobronchial
      brachytherapy for the palliation of symptoms caused by endobronchial metastases
      of non-bronchogenic primaries. PATIENTS AND METHOD: Between 1991 and 1998, eleven
      patients (female n = 3, male n = 8; age: median 66 years, range 44-81 years)
      underwent intraluminal HDR brachytherapy for histologically confirmed
      endobronchial metastases from non-pulmonary primary tumors of various sites like
      urogenital tract (n = 5), gastrointestinal tract (n = 3), ear/nose/throat (n = 2)
      and breast (n = 1). The median time between diagnosis of the primary non
      bronchogenic tumor and histopathological diagnosis of the endobronchial
      metastases was 39 months, range 1-99 months. A total dose of 15-20 Gy was
      delivered in three to four fractions of 5-6 Gy once a week. No palliative
      chemotherapy was added. RESULTS: Median follow-up after palliative brachytherapy
      was 15 months (range 1.4-59 months). Objectively, complete endoscopic response
      was observed in three (27%) patients, and in five (46%) others partial opening of
      the initially obstructed airway was achieved. Treatment was judged unsuccessful
      in three (27%) patients. No patient showed up with local progression. At date of
      analysis five patients were alive with documented residual tumor (80%) or
      complete response (20%). Relief of symptoms occurred in the vast majority of
      patients (n = 8, 73%). CONCLUSION: HDR intraluminal brachytherapy palliates
      symptoms in patients suffering from endobronchial metastases of non-pulmonary
      primary tumors. The applied treatment is a safe, effective and well tolerated
      palliative procedure leading to an improved patient quality of life.

PMID- 12240551
TI  - The electronic portal imaging system Siemens Beamview Plus versus the
      conventional verification films CEA-TVS and DuPont COL-7. A critical appraisal of
      visual image quality.
AB  - AIM: The aim of this study was the validation of the visual image quality of
      electronic portal imaging devices (EPID) and conventional verification films from
      the point of view of the end-viewers of portal films, the radiotherapists.
      MATERIAL AND METHODS: The verification image was represented in two different
      forms, viz. an electronic portal image employing Siemens Beamview Plus (on a
      computer monitor) and two different portal films using the conventional
      verification films CEA-TVS and DuPont CQL-7 (on a negatoscope). A total of 270
      image sets (simulation film and portal image) were evaluated by each
      radiotherapist, evaluation extending to 90 sets of each type of verification
      film. Each set was evaluated by three specialists in radiotherapy examining
      subjective visual image quality whereby the following aspects served as
      evaluation criteria: contrast, artifacts, determination of actual radiation field
      edge position, anatomical structures and main structural feature for the
      determination of treatment field position. In addition, the anatomical structures
      employed for visual feature correlation between reference and portal films were
      classified according to their importance. RESULTS: In general the electronic
      portal image was rated significantly "visible" or better. Only the evaluation of
      artifacts showed an appreciable disadvantage for electronic portal imaging caused
      by physical artifacts due to radiographic technique and data processing aspects
      peculiar to the Siemens Beamview Plus 1.1. and also caused by different image
      processing tools reducing physical artifacts and enhancing the visibility of
      anatomical structures and likewise of anatomical artifacts (e.g. intestinal gas).
      By calculating the Spearman correlation coefficient to detect a possible
      relationship between the different criteria of subjective visual image quality,
      the research demonstrated that artifacts when limited to a tolerable proportion
      had no significant impact on the other criteria. CONCLUSIONS: As data of EPIDS
      are digital, images can be postprocessed and enhanced in a wide variety of ways.
      Using this tool the electronic portal imaging device provides images that, in
      terms of visual image quality, are at least comparable to the two evaluated types
      of radiographic films and also have the added advantage that such images are
      stored and can be transferred electronically being presupposition for digital
      patient documentation.

PMID- 12240552
TI  - Re-irradiation of the human spinal cord.
AB  - PURPOSE: Experimental animal data give evidence of long-term recovery of the
      spinal cord after irradiation. By extrapolation of these data, re-irradiation
      regimens were designed for eight patients who required palliative radiotherapy.
      As a consequence of re-irradiation, their spinal cords were exposed to cumulative
      doses exceeding the tolerance dose. Radiobiological and clinical data are
      presented. PATIENTS AND METHOD: Eight patients were re-irradiated on the cervical
      (n = 1), thoracic (n = 5) and lumbar (n = 2) spinal cord. The time interval
      between the initial and re-treatment ranged from 4 months to 12.7 years (median:
      2.5 years). (Re-)treatment schemes were designed and analyzed on basis of the
      biologically effective dose (BED) according to the linear-quadratic model. The
      repair capacity (alpha/beta ratio) for the cervico-thoracic and lumbar spinal
      cord was assumed to be 2 Gy and 4 Gy, with a BEDtolerance of 100 Gy and 84 Gy,
      respectively. RESULTS: The cumulative irradiation dose applied to the spinal cord
      varied between 125 and 172% of the BEDtolerance. During follow-up, ranging from
      33 days to > 4.5 years (median: 370 days) none of the patients developed
      neurological complications. Seven patients died from tumor progression, and one
      patient is still alive. CONCLUSION: Long-term recovery of the spinal cord from
      radiation injury, which has been demonstrated in rodents and primates, may also
      occur in humans.

PMID- 12240553
TI  - [Ovarian suppression in the adjuvant treatment of breast cancer: GnRh analogs,
      ovariectomy or radio-castration--"the philosopher's stone" instead of "chamber of
      horrors"].
AB  - BACKGROUND: Ovarian suppression in the adjuvant treatment of perimenopausal women
      with breast cancer is an important option. The therapeutic goal can be
      accomplished by administration of GnRH-analogues, ovarectomy or radiocastration.
      PATIENTS AND METHODS: We describe the advantages and the therapy related side
      effects and compare the different treatment modalities with each other. RESULTS:
      Because of its reversibility and patient's compliance GnRH-analogues seem to be
      advantageous especially in younger premenopausal women. When longer term side
      effects of artificially induced menopause are less important, therapeutic
      alternatives such as radiocastration or ovarectomy are effective without obvious
      superiority between these options. CONCLUSION: Even in the background of the
      increasing use of GnRH-analogues radiocastration remains still a therapeutic
      alternative because of its cost-effectiveness and feasibility. This accounts
      especially for peri- or premenopausal women above the age of 45.

PMID- 12240554
TI  - Reticulocyte maturation: mitoptosis and exosome release.
AB  - During the differentiation of erythroid cells, a vast program of maturation takes
      place, leading to decay or elimination of organelles, including the nucleus,
      mitochondria, ribosomes, lysosomes, endoplasmic reticulum and Golgi apparatus.
      During the last step of red cell maturation, remaining organelles, primarily
      mitochondria and ribosomes but also vestiges of others are finally cleared from
      the cell. This cleaning session also affects specific proteins that are partially
      or entirely removed from the cell surface. The interplay of the various events
      and their causal relationships are approached here.

PMID- 12240555
TI  - Transgenic wheat plants resistant to herbicide BASTA obtained by microprojectile
      bombardment.
AB  - Wheat (Triticum aestivum) transgenic plants of an important commercial cv (Oasis)
      was obtained with an efficient and short procedure. First, the optimum conditions
      for the embryogenic calli generation from immature embryos with a high
      regeneration percentage were established. The transformation of calli was
      performed by high velocity microprojectile bombardment, using the pAHC25 plasmid,
      which contains the reporter gene beta-glucuronidase (GUS) and the selectable BAR
      gene which confers resistance to the herbicide Basta. The transformations were
      confirmed by beta-glucuronidase assay activity, PCR and Southern blot analysis.
      The efficiency of this procedure was high and similar to other reports in which
      "model" cultivar was used.

PMID- 12240556
TI  - Ciprofloxacin increases hepatic and renal lipid hydroperoxides levels in mice.
AB  - Ciprofloxacin (CFX) is an effective and relatively safe antimicrobial used in a
      variety of human infections. However, adverse drug reactions and positive results
      in genotoxic tests are reported. In order to understand the possible
      pathophysiological mechanisms of the toxic effects informed for CFX, lipid
      hydroperoxides (LOOH) -oxidative mediators of peroxidation- were quantified in
      liver and kidney of mice, after 15 to 360 minutes of the ciprofloxacin
      administration at doses of 10 mg/Kg or 100 mg/Kg by i.p. route. The peroxidation
      in the lipid fraction was evaluated by measuring the amount of hydroperoxides
      through the oxidation of 1-naphthyldiphenylphospine into its oxide and further
      quantification by high performance liquid chromatography. The initial content of
      lipid hydroperoxides (nmol/g tissue) was 253 +/- 3 in kidney and 143 +/- 12 in
      liver. CFX induced the maximal variation to 728 +/- 101 in kidney (P < 0.05) and
      315 +/- 31 in liver (P < 0.01), after 15 min of 100 mg/Kg single dose. The
      variation in the LOOH levels was significant in kidney with both doses used and
      in liver after 100 mg/Kg until 60 min after the CFX administration, and then
      gradually fell to natural levels. The results demonstrated the effect of CFX on
      lipid oxidation, an indicator of oxidative effect. A natural protective capacity
      against this oxidation, more efficient in liver than in kidney, was observed.

PMID- 12240557
TI  - Ultrastructure of the ovariole sheath in Diatraea saccharalis (Lepidoptera:
      Pyralidae).
AB  - The ultrastructure of the ovariole sheath along the Diatraea saccharalis ovariole
      was studied by scanning and transmission electron microscopy. Each ovariole is
      surrounded by an epithelial sheath, a tunica propria and scattered lumen cells.
      These three components of the ovariole sheath show different ultrastructural
      features along the ovariole, in the germarium or in the vitellarium; these
      differences are more evident in the epithelial sheath cells. The epithelial
      sheath is composed by two layers of cells, the external one running
      longitudinally and the internal one running circularly in the ovariole. These
      cells, in vitellarium, present cytoplasmic bundles of myofilaments that are
      arranged parallel to the long axis of the cells; these myofilaments are
      apparently related to the contraction movements of the follicles within the
      ovariole. The acellular tunica propria, composed of finely filamentous material,
      is attached to the adjacent follicle cells by adhesive dense plates. Between the
      epithelial sheath and the tunica propria there is a population of lumen cells,
      with morphological features of secretory activity.

PMID- 12240558
TI  - Effect of the lipophilic o-naphthoquinone CG 10-248 on rat liver mitochondria
      structure and function.
AB  - CG 10-248 (3,4-dihydro-2,2 dimethyl-9-chloro-2H-naphtho[1,2b]pyran-5,6-dione), a
      beta-lapachone analogue, modified the ultrastructure of rat liver mitochondria in
      vitro, in the absence of added oxidizable substrates. The condensed mitochondrial
      state was replaced by the orthodox or swollen state to a significant degree. The
      number of modified mitochondria depended on incubation time and quinone
      concentration, in the 25-100 microM range. Under the same experimental
      conditions, mitochondrial respiration was uncoupled as indicated by the increase
      in the rate of succinate oxidation by controlled mitochondria in metabolic state
      "4" (not in state "3"), and by the activation of latent F0F1-ATP synthase. Taking
      into account structural similarities, the results reported here may be valid for
      other o-naphthoquinones, such as beta-lapachone.

PMID- 12240559
TI  - Distribution of NADPH-diaphorase in rat mesencephalon: a light and electron
      microscopical study.
AB  - NADPH-diaphorase is a useful technique to reveal NO producing neurons at light
      microscopic level (LM). A modification of the technique using the tetrazolium
      salt BSPT as substrate, is useful to study the ultrastructure of NO neurons. The
      aim of this work was to perform a detailed analysis of NADPH-diaphorase reactive
      neurons in rat mesencephalon both at light and electron microscopic levels. NADPH
      diaphorase reactive neurons were observed in superior colliculus, in central gray
      matter, in dorsal and medial raphe and in the pedunculopontine tegmental nucleus
      using two histochemical techniques at LM. Electron microscopy showed deposits on
      membranes of the endoplasmic reticulum, Golgi apparatus and nuclear envelope of
      dorsal raphe neurons. Presynaptic and postsynaptic terminals showed deposits on
      membranous elements but postsynaptic terminals also showed deposits on the inner
      surface of their membranes. Further physiological studies are needed to clarify
      the meaning of the ultrastructural findings such as the putative interaction of
      NOS with postsynaptic proteins, receptors or membranous channels.

PMID- 12240560
TI  - Ultrastructural and cytochemical changes in the liver of primary biliary
      cirrhosis patients.
AB  - The aim of this paper is to establish whether there are cytochemical or
      ultrastructural alterations in the hepatocytes of patients with primary biliary
      cirrhosis (PBC) at stages I and II compared with the biopsies from individuals
      with normal liver. Cytochemical technique with ATP as substrate, transmission
      electron microscopy (TEM) and freeze fracture were used for the studies. In the
      normal liver biopsies the ultrastructural cytochemical localization of the
      enzymatic activity was clearly shown in the bile canaliculi. In the PBC biopsies,
      the enzymatic activity is increased in the bile canaliculi and is also present in
      the lateral membranes of the hepatocyte. TEM of the lateral surface of the
      hepatocyte in normal livers showed a smooth surface without microvilli but in PBC
      livers a large number of microvilli were seen in the lateral membranes. The Golgi
      apparatus in these patients was localized not only near the canaliculi (normal
      livers) but also in front of the microvilli. Freeze-fracture showed normal
      features in the bile canaliculus junctions of the PBC patients. We suggest that
      the localization of the enzymatic reaction, microvilli and Golgi apparatus at the
      PBC hepatocyte lateral membranes may represent a compensatory mechanism for
      derivation of bile flow and other components from the hepatocyte to the
      intercellular space.

PMID- 12240561
TI  - Improved in vitro embryo development of stenospermic grape by putrescine.
AB  - The goal of this study was to determine the effect of putrescine, added to the
      culture medium, on the in vitro development of stenospermic grape (Vitis vinifera
      L) embryos. The cross breedings of Perlon x G.C88552 and Perlon x Argentina were
      used. 0 (control), 2 and 4 mM of putrescine were added to the immature seed's
      culture medium. In Perlon x Argentina, 2 mM of putrescine statistically increased
      the percentage of total embryos, direct germination, polyembryos and normal
      plants. In Perlon x G.C88552, only 2 mM of putrescine increased all the variables
      considered, eventually tripling the percentage of normal plants obtained. The
      results suggest that the endogenous concentration of putrescine may be a growth
      limiting factor. Adding putrescine to the culture medium of immature grape seeds
      is a legitimate resource to significantly increase the results of this technique.

PMID- 12240562
TI  - Pattern of hypothyroid disorders in Ethio-Swedish Children's Hospital (ESCH).
AB  - All children with thyroid disorder attending the endocrinology clinic of the
      Ethio-Swedish Children's Hospital (ESCH), Addis Ababa in 1996 were included in
      this study. One hundred twenty six new patients from all over the country were
      referred to the clinic for thyroid disorder and 31 patients (24%) were found to
      have hypothyroidism. Seventeen (13%) had congenital hypothyroidism while the rest
      14(11.5%) were categorised to have juvenile hypothyroidism. Thyroid dysgenesis is
      the commonest cause of permanent hypothyroidism. Mental retardation was the
      accompanied manifestation in all the cases with thyroid agenesis except in two
      children. Mental retardation being the commonest permanent sequelae in aplastic
      hypothyroidism is of utmost concern and its prevention is desirable, therefore
      high index of clinical suspicion with a close observation for early feature of
      congenital hypothyroidism is warranted for early intervention and in the future
      nation wide screening for hypothyroidism is recommended.

PMID- 12240563
TI  - Obstructed labor at a district hospital.
AB  - A retrospective analysis of all deliveries that occurred at Jimma hospital, south
      western Ethiopia from September 1990 to May 1999 was conducted to determine the
      incidence, maternal and perinatal outcome, sociodemographic and clinical
      characteristics of mothers with obstructed labor. Seven percent (945/13,425) of
      the deliveries were complicated with obstructed labor with an overall increasing
      trend noted during the study period. Sixty seven percent of the cases were
      primigravida and grand multiparous mothers. Fourteen percent of obstructed labor
      occurred among teenage pregnant mothers. Forty four percent of the cases had no
      antenatal care while 35.1% had antenatal care. Cephalopelvic disproportion (CPD)
      was responsible for 80.6% of the cases, malpresentations accounting for the
      remainder, shoulder presentation being the commonest (11.5%). Fifty eight percent
      of the CPD cases were among the primigravida but para two to four mothers were
      not immune accounting for 25.7% of the cases, the rest being grand multipara,
      (15%). Fifty seven percent of the ruptured uterus cases were para two to four
      mothers while primigravids accounted for 7.2%. Maternal mortality was 9.1% while
      62.1% of the perinates died with only 12.5% of the neonates having normal first
      minute apgar scores. Obstructed labor was the commonest cause of maternal and
      perinatal mortality at the hospital during the study period responsible for 45.5%
      and 37.4% of the deaths respectively. Any attempt to reduce maternal mortality at
      the hospital must comprehensively address the issue of obstructed labor, identify
      risk groups of mothers for this peripartum complication and design preventive
      strategies.

PMID- 12240564
TI  - Co-infection of Onchocerca volvulus and intestinal helminths in indigenous and
      migrant farmers in southwest Ethiopia.
AB  - A cross-sectional survey on onchocerciasis and intestinal helminthic infections
      was conducted in two villages around the town of Teppi, south-west of Ethiopia on
      a total of 308 subjects of which 180 indigenous and 128 migrant settlers aged 10
      years and above who lived in the area for at least 5 years. Of the total study
      subjects, 65% were males. The majority (64%) of the study subjects were in the
      age range of 21-40 years. The results of stool and skin snip examinations for
      ova/parasite and microfilaria revealed that, 62% (190) and 81% (248) of the study
      subjects were positive for intestinal parasites and microfilariderma
      respectively. Fifty percent (154) of the total subjects in the two villages had
      both onchocerciasis and intestinal helminthic infections. However, 80% (94/118)
      of the stool negative subjects also had onchocerciasis indicating that
      onchocercal skin infection has no significant influence on the acquisition of
      intestinal helminthic infections or vice versa [(relative risk 1.04, 95% CI 0.91,
      1.18) P > 0.05]. Sixty-five percent (161/248) of the total skin snip positive
      individuals had microfilarial load of > 10 mf/mg of skin snip. The proportion of
      multiple infections with 2 or more intestinal helminthes was recorded in 51%
      (96/190) of individuals positive for intestinal parasitosis. There was a
      significant (x2 = 8.41, P < 0.005) difference in the onchocerciasis infection
      rate among indigenous (88%) and migrant (75%). No direct association was observed
      between onchocerciasis and intestinal parasitosis in the two study groups
      (indigenous and migrant settlers). The public health significance of coexistence
      of the two diseases, and the need for intensive control measures are discussed.

PMID- 12240565
TI  - Epidemiological studies on intestinal schistosomiasis in Wondo Genet, southern
      Ethiopia.
AB  - A cross-sectional epidemiological survey was made on intestinal schistosomiasis
      due to Schistosoma mansoni in Wondo Genet, southern Ethiopia, in 1999 to generate
      preintervention parasitological and malacological baseline data to be used as a
      reference in evaluation of community-based pilot control trial to be launched
      using wild-growing Endod. A total of 3000 stool specimens were collected from
      schoolchildren enrolled in 14 schools and microscopically examined using Kato
      method. The overall prevalence and intensity of schistosomiasis mansoni was 34.6%
      and 184 eggs per gram of stool (EPG), respectively. Children excreting
      Schistosoma mansoni eggs were found in all of the 14 schools surveyed with a
      prevalence of infection ranging from 1.9% in Abaye School to 80.6% in Shesha
      Kekele School. The overall prevalence of S. mansoni infection among males and
      females was 38.4% and 27.3%, respectively (P = 0.0001, 95% C.I = 7.5%-14.7%)
      where as the intensity of infection was 186 EPG and 181 EPG, respectively (P =
      0.8045, 95% C.I = 1.17%-1.23%). Malacological surveys of 27 water contact sites
      revealed the occurrence of Biomphalaria pfeifferi in 8 sites out of which 3
      harbored infected snails shedding schistosome cercariae. The necessity for
      initiating community-based sustainable control programme is discussed.

PMID- 12240566
TI  - Sexuality and contraception among never married high school students in Butajira,
      Ethiopia.
AB  - Cross-sectional survey using a self-administered anonymous questionnaire was
      conducted to assess knowledge, attitude and practice of contraception and
      sexuality. The questionnaire was filled out in April 2000 by 752 high school
      students in Butajira, Ethiopia. The mean age of the subjects was 17.1 years. One
      hundred thirteen never married students (17.5%) claimed to have experienced
      intercourse; 22.0% of boys and 8.8% of girls. Sexual abstinence was not dictated
      by perception of risk. About 78% of boys and 91% of the females did not use
      modern contraceptives at their last sexual intercourse. Nine female students
      claimed to have been pregnant: two had delivered and seven had induced abortion.
      The most important reasons for non-use of contraception were lack of adequate
      knowledge, partner refusal, perception of diminished pleasure and embarrassment
      to buy. Seventy-one percent of the respondents knew at least one contraceptive
      method. Over half of the students had no source of information on sexuality and
      for 25.9% school was the main source of information. The attitude to sexuality
      was conservative, but liberal to introduction of sex-education at secondary
      schools. Higher percentage of boys admitted that they had exaggerated their
      response on sexual matters; girls admitted under-reporting. It is recommended
      that sex and family life education be discussed openly in schools and included in
      curricula.

PMID- 12240567
TI  - Forearm bone non-union and its management.
AB  - A total of 125 patients with forearm (radio-ulnar) bone compound fractures
      resulting from missile injuries were examined 8 to 16 weeks after the time of
      injury with the objective of finding out the rate and causes of non-union.
      Initial management in each case was circular POP with windows for wound care or
      posterior slabs made of POP, Cramer-wire, or wood at random. Out of these, 22
      (17.5%) patients had non-union. All were male, mean age 26 years, in good
      nutritional state and no underlying chronic illnesses found on routine
      examination. Fourteen had ulnar bone and 8 radial bone non-union. Four of the
      patients with ulnar non-union had both radio-ulnar fracture. All 22 patients had
      haematocrit values > 30%, had no associated injury and none had vascular injury
      at site of wounding. Seven (32%) had wound infection. All wounds healed within 2
      4 weeks after injury. Diagnosis of non-union was made by clinical examination and
      x-rays of the forearm. All the 22 cases were operated on under general
      anaesthesia and exploration revealed that 18 had bone defects ranging from 1 cm
      to 5 cm, 2 had soft tissue interposition and 2 had failure of reduction as the
      obvious cause of non-union. Cancellous, slivered iliac bone grafts were made in
      all cases to bridge gaps and induce osteogenesis. Stabilization was made by rush
      pins used as intramedullary nails in 12 cases in addition to either long or short
      arm plaster of paris casts in all cases. There was no post-operative infection
      including the donor site and all had well healed wounds and good union 8-10 weeks
      later. Bone defect is the most common cause of non-union of forearm bone
      fractures resulting from missile injury and early slivered cancellous bone graft
      is effective in the treatment of non-union.

PMID- 12240568
TI  - Accidentally discovered large metallic intra-orbital foreign body.
AB  - A 6.2 cm long and 2.7 cm thick metallic foreign body was accidentally found and
      removed from a 62 years old man. He was sent to a minor operation theater for
      repair of left lower lid laceration secondary to trauma after a fight. Subsequent
      investigation, management, patient follow-up and outcome are discussed.
      Importance of careful history taking, thorough physical examination and proper
      investigations are stressed.

PMID- 12240569
TI  - Peripheral primitive neuroectodermal tumor presenting in the retroperitoneum: a
      case report with immunohistochemical study.
AB  - It is now believed that malignant peripheral primitive neuroectodermal tumor
      (PNET) form a distinct tumor entity from other malignant small round cell tumors
      exhibiting neuroectodermal differentiation by morphologic, immunohistochemical or
      electron microscopic analyses. A 17-year-old Ethiopian boy was found to have a
      big upper extra osseous retroperitoneal tumor mass not associated with peripheral
      nerve that had infiltrated the body of the pancreas. Histologic sections from
      excised biopsy showed neoplastic cells with a high nuclear-cytoplasmic ratio and
      had an indistinct cytoplasm with numerous Homer-Wright rosettes.
      Immunohistochemically, isolated tumor cells and the centre of rosettes disclosed
      strong positivity to neural markers, synaptophysin and chromogranin. To the best
      of our knowledge, this case report represents the first patient described in
      Ethiopia.

PMID- 12240570
TI  - Drug-resistant tuberculosis in Ethiopia: problem scenarios and recommendation.
AB  - Tuberculosis (TB) is a major public health problem in Ethiopia. This review is
      prepared to indicate possible future challenges related to tuberculosis control
      and it includes previous reports of drug-resistant surveys in Ethiopia. Drug
      resistant TB, both initial and acquired, was reported from different regions of
      the country. In studies from 1984 to 2001, the initial resistance to isoniazid
      ranges from 2% to 21% and initial resistance to streptomycin ranges from 2 to
      20%. Multidrug-resistance (MDR) TB defined as resistance to at least isoniazid
      and rifampicin was also reported in about 1.2% of new cases and 12% of re
      treatment cases. In all studies which included ethambutol susceptibility test,
      ethambutol resistance is either nil or very low (below 0.5%). All MDR isolates
      were susceptible to ethambutol. Treatment and re-treatment regimens recommended
      by the National TB/Leprosy Control Program could be effective on all cases other
      than those with MDR-TB. MDR-TB is difficult to cure. Therefore, special emphasis
      should be given to control the spread of MDR-TB. Lack of control efforts may lead
      to the increased resistance to both first- and second-line drugs. A well
      supported and controlled special treatment unit, which uses both first-line and
      second-line drugs is required for a proper management of these cases and for
      effective control of the spread of MDR-TB. A uniform susceptibility to ethambutol
      can be taken as an advantage to develop standard low-cost re-treatment regimen
      for MDR-TB patients.

PMID- 12240571
TI  - The Ethiopian scene and prospects for research.

PMID- 12240572
TI  - A randomized clinical trial of the success rates of bilamellar tarsal rotation
      and tarsotomy for upper eyelid trachomatous trichiasis.
AB  - A randomized clinical trial study was conducted to compare the success rates of
      two surgical methods: Bilamellar Tarsal Rotation (BTR) and Tarsotomy (Transverse
      Tarsotomy and lid margin Rotation = TTR) for trachomatous trichiasis of the upper
      lid; where success was defined as no lash/eyeball contact in all positions of
      gaze, complete lid closure, no under or over correction. The study was conducted
      at Minellik II Hospital, Addis Ababa. Two hundred fifty six upper eyelids of 153
      patients with entropion/trichiasis related to trachoma were enrolled in the two
      groups. Patients were randomly allocated for the BTR (124) and TTR (132)
      procedures. Out of these, 237 (92.6%) came for the third month follow-up. One
      hundred fifteen (48.5%) lids underwent BTR and the remaining 122 (51.5%)
      underwent TTR. In total, from 141 patients who came for the last follow up, 109
      (77.3%) were females. BTR procedure was found to be successful in 25 (86.2%) of
      the eyelids with minor trichiasis and 74 (86.0%) of those with major trichiasis;
      the difference between patients who had had minor and major trichiasis (X2 =
      0.08, P = 0.772) was not statistically significant. TTR was successful in 39
      (95.1%) of the eyelids with minor trichiasis and 68 (84.0%) of those with major
      trichiasis, again no statistically significant difference was observed for minor
      and major trichiasis (X2 = 3.15, P = 0.379). There was no statistically
      significant difference in recurrence between BTR and TTR (X2 = 0.14, P = 0.711).
      Complications such as lid-notching, pyogenic granuloma, etc. were observed more
      in BTR than in TTR and this was statistically significant (X2 = 9.54, P = 0.002).
      In conclusion, the results show that TTR is equally successful in minor and major
      trichiasis and has fewer complications than BTR at three months of follow-up.

PMID- 12240573
TI  - Patterns of isolation of common gram positive bacterial pathogens and their
      susceptibilities to antimicrobial agents in Jimma Hospital.
AB  - Gram positive bacteria are frequently emerging as antibiotic resistant pathogens,
      causing serious infections than ever before in the ill and debilitated patients.
      The pattern of isolation and the antimicrobial susceptibilities of common Gram
      positive cocci including Staphylococcus aureus, coagulase negative staphylococcus
      (CoNS), Streptococcus pyogenes, Enterococcus species and Streptococcus pneumoniae
      was investigated between January 1997 and June 2000 in Jimma Hospital. Of the 500
      specimens collected from children and adults, 116 (23.2%) consisted of one or
      more of the above organisms. The following strains: Staphylococcus aureus, 47
      (40.5%), CoNS, 36 (31.0%), Streptococcus pneumoniae, 26 (22.4%) Streptococcus
      pyogenes, 5 (4.3%) and Streptococcus faecalis, 2(1.7%) were isolated from
      different specimens including pus, sputum, urine, stool, blood and
      oro/nasopharyngeal swabs of patients. The in vitro activities of 14 different
      antibiotics including penicillin G, ampicillin, cloxacillin, cephalothin,
      gentamicin, kanamycin, tetracycline, chloramphenicol, erythromycin, trimethoprim
      sulfamethoxazole, streptomycin, methicillin, vancomycin and clindamycin was
      determined against the clinical bacterial isolates. The antimicrobial activities
      were evaluated by agar diffusion technique using Mueller-Hinton agar according to
      NCCLS recommendations. The majority of the pathogens, 59(50.9%) were recovered
      from upper respiratory tract infections and 17 (14.6%) from the lower respiratory
      tract. The resistance patterns of S. aureus, CoNS, S. pneumoniae and enterococci
      to penicillin was 91.5%, 94.4%, 7.7% and 100% respectively. Penicillin,
      ampicillin and cloxacillin showed low effects (< 60%) on both S. aureus and CoNS.
      Multi-drug resistance was observed in all the gram-positive isolates, especially
      higher in staphylococcus species. All isolates of S. aureus (100%) were
      susceptible to vancomycin, clindamycin and gentamicin. In order to reduce
      morbidity and mortality due to antibiotic resistance susceptibility testing
      should be performed for the proper management of bacterial infections. This
      entails the need for national surveillance to monitor antibiotic resistance in
      bacteria by susceptibility testing using reliable methods.

PMID- 12240574
TI  - Management of traumatic arterio-venous fistulas, experience in Armed Forces
      General Hospital, Addis Ababa.
AB  - In Armed Forces General Hospital from March to December 1999, 53 patients were
      operated for Arterio-venous fistula. All were males, their age ranging from 19 to
      46 years, average 27 years. The diagnosis of arterio-venous fistulas was
      established clinically. The pathological distribution of the lesions were:
      23(43.4%) Arterio-Venous aneurysm; 11(20.75%) Arterio-Venous fistula, 19(35.85%)
      Arterial false aneurysms. The anatomical location was: 15 femoral, 10 Tibial, 6
      poplitial, 6 brachial, 4 Axillary, 1 ulnar, 7 external carotid and 1 occipital.
      The types of surgical procedures performed were: 29 (54.72%) excision of the
      arterio-venous fistula and aneurismal sac with arterial restoration by end to end
      anastomosis and/or saphenous vein graft, 16(30.19%) by excision of arteriovenous
      fistula and quadriple ligation of small vessels, 8(15.09%) excision of the false
      aneurismal sac and lateral repair of the artery (lateral arterioraphy). During
      the post operative period the patients were followed for three months, and we had
      the following results based on the clinical outcome criteria; 37(69.81%)
      excellent, 15(28.3%) good and 1(1.89%) fair.

PMID- 12240575
TI  - A two years retrospective review of episiotomy at Jimma Teaching Hospital,
      southwestern Ethiopia.
AB  - Episiotomy is one of the most commonly performed obstetric interventions. The
      practice has been on the rise since hospital confinement became the tradition of
      childbirth. Unlike the rising cesarean section rate the rise in episiotomy rate
      has not been challenged. There is evidence that episiotomy rate of over 30% is
      not acceptable and it should be done on selective basis than routinely. A
      retrospective review of all deliveries that took place at Jimma teaching Hospital
      from Sept 23, 1998 to Sept 23, 2001 was done to determine the episiotomy rate and
      factors influencing the practice. The overall incidence of episiotomy among 2861
      vaginal deliveries was 25%. The incidence of episiotomy by specific procedure
      was: 6 out of 21 forceps deliveries (29%), 30 out of 101(30%) vacuum deliveries
      and 8 out of 71(11%) destructive deliveries. 47% of nulliparas and 5% of
      multiparas needed episiotomy. The mean ages of patruents delivering by episiotomy
      and spontaneous vertex delivery were 22 +/- 4 and 26 +/- 6 years respectively.
      The difference was significant (p < 0.0001). There was not statistically
      significant difference in mean birth weight, head circumference and gestational
      age between the two groups. The incidence of episiotomy in this study was low
      compared to the findings of other studies from both developing and developed
      countries. Similar studies are warranted in other hospitals of the country to
      address the practice pattern. Prospective studies should be done to establish
      indications and outcomes of episiotomy.

PMID- 12240576
TI  - Sonographic diagnosis of hypertrophic pyloric stenosis: preliminary experience.
AB  - The value of ultrasound diagnosis for suspicion of infantile hypertrophic pyloric
      stenosis (HPS) was assessed in three consecutive years using ultrasound
      measurement of pyloric muscle thickness (PMT), pyloric diameter (PD) and pyloric
      length (PL) in Tikur Anbessa Hospital which is a tertiary referral and teaching
      hospital. Among all patients 39 patients (36 males and 3 females) had Infantile
      Hypertrophic Pyloric Stenosis confirmed by surgery, with male to female ratio of
      12:1. Ultrasound correctly diagnosed all of the cases. Sixty- six patients were
      negative by Ultrasound, Barium meal studies and clinical follow up. The mean
      Pyloric Muscle Thickness (4.46 Vs 1.81), Pyloric Length (19.1 Vs 11.55) and
      Pyloric Diameter (14.05 Vs 8.4) between patients with and with out pyloric
      stenosis were significantly different (p < 0.05). A PMT of 3 mm and above was
      observed in all cases of HPS, and was never observed in the absence of HPS (100%
      sensitivity and specificity). A pyloric muscle thickness of 3 mm and above is
      recommended as a diagnostic cutoff and upper gastrointestinal series (UGIS) can
      be reserved for those who might fall in the grey zone (i.e. PMT of 2-3 mm).

PMID- 12240577
TI  - Acute appendicitis in Yirgalem Hospital, southern Ethiopia.
AB  - The prevalence of appendicitis shows a marked variation between populations. The
      aim of this study is to determine the rate of prevalence of acute appendicitis in
      Yirgalem Hospital, in Southern Ethiopia. A retrospective analysis was undertaken
      on 200 cases of acute appendicitis surgically managed at Yirgalem Hospital from
      January 1997 to December 1999. During this period the disease accounted for 27.9%
      of the operations for acute abdominal emergencies and for 1.1% of total hospital
      admissions. There were 159 males and 41 females giving a male to female ratio of
      3.9:1. The mean age was 25.6 +/- 10.9 years (range 4-90 years). The average
      duration of illness at presentation and hospital stay were 3.4 +/- 1.7 and 7.1 +/
      5.3 days, respectively. All the cases presented with abdominal pain and a shift
      of the periumbilical abdominal pain to the right lower quadrant was found in the
      majority. Right lower quadrant tenderness was the leading physical finding. The
      rate of simple and perforated appendicitis were 45.5% and 44%, respectively.
      Thirty-two per cent of the patients had postoperative wound infection. Out of the
      200 patients operated upon for acute appendicitis 8 (4%) died. The study showed
      that the prevalence of acute appendicitis was low in Yirgalem Hospital and the
      results of the study were compared with those from elsewhere.

PMID- 12240578
TI  - Endemic existence of rabies in Ethiopia.
AB  - The study on the prevalence of rabies was conducted on a retrospective data
      gathered from EHNRI rabies diagnostic laboratory Addis Ababa, in the years 1979
      1987. During this period a total of 8036 animals were brought to the rabies
      diagnostic laboratory. Ninety one percent (7329) of these animals were dogs. The
      remaining 8.8% (707) comprised of cats, domestic animals (donkeys, cows, sheep)
      and wild animals (monkeys, jackals and hyenas). Out of 7329 dogs examined 832
      were positive for rabies. Dogs accounted for the majority of animal rabies
      (94.01% of the total positive animals). The remaining 5.99% (53) of the animals
      diagnosed with rabies-comprised of cats, domestic animals and some wild animals.
      A total of 15,940 people were given post exposure anti-rabies prophylaxis
      treatment that came from different parts of the country in the years 1979-1987.
      The prevalence rates of rabies were found to be higher soon after dogs' breeding
      seasons. Such an observation indicates that among dogs infection, transmission
      through biting is significant during the breeding season. However, despite the
      high incidence of rabies in Ethiopia, only 320 people were reported to have died
      of rabies in the years 1979-1984. This supports, the hypothesis that there is a
      lack of appropriate reporting system on prevalence of rabies and its impact on
      humans in Ethiopia.

PMID- 12240579
TI  - Congenital absence of the gallbladder and the cystic duct.
AB  - A 47 years old female with congenital absence of the gallbladder and the cystic
      duct was presented. The diagnosis was confirmed by exploratory laparatomy, common
      duct tube cholangiography, and ultrasonography. Most of the operated cases of
      congenital absence of the gallbladder are symptomatic, and they get relief after
      common duct exploration. Although the biliary tree is normal on inspection at
      exploration, it is believed that the symptomatology may have root in congenital
      abnormality of function. Treatment of the agenesis of the gallbladder as
      described in earlier days has been discussed. In the present situation, specially
      in a country like Ethiopia where long time care of internal drains is a worrisome
      problem, and a major point for concern, the author believes choledocho-enteric
      anastomosis to be a good solution.

PMID- 12240580
TI  - An ovarian tumor larger than the patient's body weight.
AB  - Surface epithelial-stromal tumors constitute by far the most important group
      among all ovarian neoplasms. Sixty-four kilogram left ovarian serous cystadenoma
      was removed from a forty-nine kilogram weighing Ethiopian woman. She presented
      with twenty-five years history of abdominal swelling. She had extreme degree of
      difficulty in bearing her weight, which resulted in keeping her to the house.
      This unusually big tumor is discussed with clinicopathologic correlation and
      literature review.

PMID- 12240581
TI  - Integrated management of childhood illness: a review of the Ethiopian experience
      and prospects for child health.
AB  - Pneumonia, diarrhea, malaria, measles and malnutrition account for over 70% of
      the 11.5 million deaths and 80-90% of sick child consultations in developing
      countries. These conditions often occur in combinations requiring a holistic
      approach of assessment, treatment and caretaker counseling. The Integrated
      management of Childhood Illness (IMCI) strategy has been developed to address
      these needs. Ethiopia contributed immensely to the development of IMCI and
      officially adopted it in 1997. Progress in terms of training and geographic
      expansion has been limited. This analytical review has been made to identify ways
      to strengthen and sustain IMCI implementation. Data were collected from published
      and unpublished information sources relevant to the IMCI strategy in Ethiopia and
      through key informant interviews with representatives of Federal Ministry of
      Health and its partners. The rationale for IMCI in Ethiopia, past, present and
      planned IMCI activities, related policies and strategies, strengths and
      weaknesses, and priorities have been analyzed and recommendations developed. The
      review identified that most of the childhood deaths and 40% of all disability
      adjusted life years lost are associated with pneumonia, diarrhea, malaria,
      measles and malnutrition. IMCI has, thus, been adopted in 1997 as the main
      strategy for improving child health and included in the Health Sector Development
      Programme of the country. Three regions have piloted the strategy and their
      experience used to develop plans for expansion to other regions and also to
      initiate IMCI activities related to family and community practices. Much has been
      learnt from the pilot phase and from the country's involvement in the initial
      development of the strategy. There are critical gaps that need to be addressed
      for the IMCI strategy to exert the desired impact on child health in Ethiopia.
      The HIV/AIDS algorithm should be validated and included in the IMCI guidelines.
      There is a need for scaling-up training activities and carry out follow-up after
      training in 4-6 weeks. A standardized checklist needs to be developed and
      integrated into existing supervision protocols and this be used to supervise IMCI
      implementing facilities regularly. Strategies to train and involve lower level
      health cadres in IMCI implementation and modify the standard IMCI course to suit
      senior physicians and programme managers are required. Standard recording and
      reporting tools need to be developed and IMCI classifications harmonized with
      current MOH guidelines. Essential IMCI drugs should be available to health
      facilities. Interventions need to be identified and tools developed to support
      the IMCI implementation at community and family level. Continued advocacy for
      IMCI is required to secure support from all stakeholders. Planning for IMCI
      should set clear milestones and take into consideration central and regional
      capacities and ways to strengthen them. Operations research is required to guide
      policy development and planning for IMCI implementation. It should be included as
      an essential activity in strategic and annual plans for IMCI implementation in
      Ethiopia.

PMID- 12240582
TI  - Time's up.

PMID- 12240583
TI  - Back to the future.

PMID- 12240584
TI  - Cold comfort. Interview by Alison Moore.

PMID- 12240585
TI  - Smile please.

PMID- 12240586
TI  - A dual role.

PMID- 12240587
TI  - A question of conduct. Interview by Charlotte Alderman.

PMID- 12240589
TI  - Face value.

PMID- 12240588
TI  - Going Dutch.

PMID- 12240590
TI  - Far from home.

PMID- 12240591
TI  - Ready, steady...go.

PMID- 12240593
TI  - Back to the drawing board.

PMID- 12240592
TI  - Talk about it.

PMID- 12240594
TI  - Taking a Direct line.

PMID- 12240595
TI  - The next level. Interview by Steven Black.

PMID- 12240596
TI  - Make or break.

PMID- 12240597
TI  - Breathing space.

PMID- 12240599
TI  - The mifepristone-inducible gene regulatory system in mouse models of disease and
      gene therapy.
AB  - The mifepristone (Mfp)-inducible gene regulatory system is designed to allow
      control of the spatiotemporal expression of transgenes in vivo in a ligand
      dependent manner. This regulatory system is composed of two components: (1) a
      chimeric transactivator protein that activates transgene transcription only in
      the presence of the progesterone antagonist Mfp, and (2) a target transgene
      placed in the context of a promoter which is responsive only to the Mfp-bound
      chimeric transactivator. Incorporation of the components of the Mfp-inducible
      gene regulatory system into transgenic mice has resulted in the establishment of
      several novel, Mfp-dependent models of disease. Similarly, adaptation of the Mfp
      inducible system for use in gene knockout models has resulted in the development
      of new gene ablation technology which is both tissue-specific and Mfp-dependent.
      Additionally, the Mfp-inducible gene regulatory system has been used in animal
      experiments involving somatic gene therapy, where it has shown considerable
      promise in the regulation of both reporter and therapeutic gene expression. This
      review focuses on recent application of the Mfp-inducible system to transgenic
      models, gene knockout models, and somatic gene therapy experiments. In so doing,
      it demonstrates the considerable promise that future use of this system holds for
      better understanding and treatment of human disease.

PMID- 12240598
TI  - Recent advances in inducible expression in transgenic mice.
AB  - In order to accurately analyze gene function in transgenic mice, as well as to
      generate credible murine models of human diseases, the ability to regulate
      temporal- and spatial-specific expression of target genes is absolutely critical.
      Pioneering work in inducible transgenics, begun in the 1980s and continuing to
      the present, has led to the development of a variety of different inducible
      systems dedicated to this goal, the shared basis of which is the accurate
      conditional expression of a given transgene. Recent advances in inducible
      transgene expression in mice are discussed.

PMID- 12240600
TI  - The difference between Colour Doppler Velocity Imaging and Power Doppler Imaging.

PMID- 12240601
TI  - [Hepatic encephalopathy].

PMID- 12240602
TI  - [Morphological and functional changes in the digestive mucosa due to aging].

PMID- 12240603
TI  - Gender, culture and AIDS. A Ugandan mother speaks out.

PMID- 12240604
TI  - Going to an AIDS conference.

PMID- 12240605
TI  - Are you covered? Travel and vacations with a major illness or disability.

PMID- 12240606
TI  - Acute pain services--how effective are we?

PMID- 12240607
TI  - Patient or PAC?

PMID- 12240608
TI  - Meningococcal chemoprophylaxis for anaesthetists.

PMID- 12240609
TI  - Sevoflurane usage.

PMID- 12240610
TI  - An apparently normal looking valve as a cause of rebreathing.

PMID- 12240611
TI  - Critical incident involving the Draeger Cato ventilator.

PMID- 12240612
TI  - Oxygen failure alarms on modern anaesthetic machines.

PMID- 12240613
TI  - When and by whom was the curved tip of a gum-elastic bougie first introduced.

PMID- 12240614
TI  - Midazolam for PONV. What's new?

PMID- 12240615
TI  - Spinal opioids, midazolam and antiemesis.

PMID- 12240616
TI  - Positioning for radial artery cannulation.

PMID- 12240617
TI  - Old wine in a new bottle?

PMID- 12240618
TI  - Foriegn language drug labelling.

PMID- 12240619
TI  - Penicillin kills.

PMID- 12240620
TI  - A talisman to ward off the bad anaesthetics.

PMID- 12240621
TI  - Bloody stool.

PMID- 12240622
TI  - We can all fight AIDS. 20 ways to make a difference.

PMID- 12240623
TI  - Alternative splicing in the testes.
AB  - Germ-cell differentiation is an ideal process for studying the effects of
      alternative splicing and there are examples of alternative splicing of genes
      involved in gene regulation and signal transduction at every stage of the
      spermatogenic pathway. A network of testes-specific splicing factor interactions
      has been uncovered and combining our knowledge of these RNAs and proteins should
      lead to an understanding of the regulation of alternative splicing and male
      fertility.

PMID- 12240624
TI  - Methotrexate-related nonnecrotizing multifocal axonopathy detected by beta
      amyloid precursor protein immunohistochemistry.

PMID- 12240625
TI  - Augustus Volney Waller.

PMID- 12240626
TI  - Protocol for the examination of specimens from patients with hematopoietic
      neoplasms of the bone marrow: a basis for checklists.

PMID- 12240627
TI  - Pathologic quiz case. Cystic and solid ovarian tumor in a 43-year-old woman.

PMID- 12240628
TI  - Pathologic quiz case. Uterine polypoid mass in a postmenopausal patient following
      tamoxifen treatment for breast cancer.

PMID- 12240629
TI  - Pathologic quiz case. Unusual lung mass in a 21-year-old man.

PMID- 12240630
TI  - Pathologic quiz case. Recurrent headache in a 39-year-old woman.

PMID- 12240631
TI  - Benign metastasizing giant cell tumor.

PMID- 12240633
TI  - Follicular colonization by follicular lymphoma.

PMID- 12240632
TI  - Crystalline histiocytosis in hereditary cysinosis.

PMID- 12240635
TI  - A controlled trial of arthroscopic surgery for osteoarthritis of the knee.

PMID- 12240636
TI  - A controlled trial of arthroscopic surgery for osteoarthritis of the knee.

PMID- 12240637
TI  - Collaborative effort.

PMID- 12240638
TI  - Botulism beaten.

PMID- 12240639
TI  - Drug resistance and the treatment of experienced patients.

PMID- 12240640
TI  - Antiretroviral therapy: when to start & what to start with.

PMID- 12240641
TI  - Antiretroviral treatment in developing countries.

PMID- 12240642
TI  - The global HIV/AIDS pandemic 2002: a status report.

PMID- 12240643
TI  - Pharmacology and drug interactions: a progress report.

PMID- 12240644
TI  - Management of hepatitis C: a review of the NIH Consensus Development Conference.

PMID- 12240645
TI  - [From the history of the Academy of Military Medicine: II--the admissions and
      surgery department].

PMID- 12240646
TI  - The skull of Orce: parietal bones or frontal bones?

PMID- 12240647
TI  - Novel biosensors in environmental and food samples.

PMID- 12240648
TI  - The electrochemical characterisation of benzyl mercaptan-modified Au(111):
      structure and copper deposition.
AB  - The behaviour of benzyl mercaptan self-assembled monolayers on Au(111) in
      sulfuric acid solution was studied using cyclic voltammetry and in situ scanning
      tunnelling microscopy. Modification of the Au(111) surface in an ethanolic
      solution of benzyl mercaptan leads to a disordered monolayer. However, by partial
      reductive desorption a striped c (15 x sqrt [3]) and a (2 x sqrt [3]) structure
      were obtained. The disordered benzyl mercaptan film was also used for the study
      of copper deposition. At -0.02 V versus SCE, that is in the underpotential
      deposition region, monoatomic high islands appear on the surface. Bulk deposition
      of copper starts at -0.08 V versus SCE with the growth of dendrites underneath
      the thiol film. At higher overpotentials, the growth of three-dimensional copper
      clusters commences.

PMID- 12240649
TI  - Reactant adsorption in cyclic staircase voltammetry on spherical microelectrodes.
      Reversible redox reactions.
AB  - On spherical microelectrodes, cyclic staircase voltammograms of reversible redox
      reactions complicated by the reactant adsorption depend on lateral interactions
      in the monolayer. Attraction forces increase the separation between the main wave
      and the post-peak, while the repulsion prevents the resolution of responses of
      the surface and volume reactions. The theoretical relationships between the
      dimensionless responses and the dimensionless adsorption constant, the relative
      surface adsorption capacity, the Frumkin coefficient and the electrode sphericity
      are given.

PMID- 12240650
TI  - Laboratory development and field evaluation of a new diffusive sampler to collect
      nitrogen oxides in the ambient air.
AB  - Diffusive samplers for the determination of NO(x) and NO2 based on collection on
      a coated carbon paper filter have been developed. NO is first oxidized to NO2 and
      then collected on the reactive surface. When NO2 and NOx samplers are exposed
      simultaneously, NO can be calculated by difference. The sampler has been derived
      from a Palmes design as recently modified by Bertoni et al. for the determination
      of BTX (benzene, toluene, xylenes). Laboratory tests were conducted in controlled
      atmosphere to evaluate linearity, uptake rate, face velocity effects, sample
      stability, influence of relative humidity, precision and accuracy. The samplers
      are capable of reliable measurements of the two species at common levels of a
      polluted atmosphere in urban settings yielding average concentration levels over
      1 month and beyond. The uptake rate of NO2 was found to be 11.7 mL/min in a very
      good agreement (within 5%) with the value calculated from theory. The measured
      uptake rate for NO(x) was determined in experiments involving sampling at
      different concentration levels in comparison to chemiluminescence (CL)
      measurements. The precision of the measurements for co-located passive samplers
      was better than 5%. The accuracy of the data collected is within +/-20% of the
      actual value measured by CL. The laboratory and field results show that the NO(x)
      and NO2 samplers meet the data quality goal requested by the first EU Directive
      1999/30/EU for these pollutants.

PMID- 12240651
TI  - [The association movement of the Brazilian graduate nurses in the first half of
      the 20th Century].
AB  - The present study is a socio-historical research. It discusses the association of
      trained nurses in Brazil, which was represented by opponent groups, and the
      struggle of these groups in introducing their positions and viewpoints in the
      professional organizations. The investigation focuses the period of time between
      the foundation of the Brazilian Association of Nursing (ABEn), in 1926, until the
      first half of the twentieth century. Despite the political and doctrinal levels,
      which guided nursing strategies to fortify their positions in this environment,
      the articulation of opponent groups in the achievement of common professional
      objectives promoted the regulation and redefinition of the nursing profession.

PMID- 12240652
TI  - [Collective responsibility of nurses in their involvement in their professional
      organizations].
AB  - This study has as its objective the discussion of the nursing professionals'
      responsibility regarding their participation in professional associations, such
      as the Brazilian Association of Nursing (ABEn), the Regional Board of Nursing and
      the Nursing Union. The investigation was carried out with nurses from a private
      and a public educational institution and also from a private institution of
      assistance. As a result, it was verified that the participation of nurses in the
      organizations mentioned above is still scarce, but there is already some
      awareness of the need for integrating them.

PMID- 12240653
TI  - [The life and work of Zaira Cintra Vidal].
AB  - This is a social-historical study that aims at describing the trajectory of Zaira
      Cintra Vidal, her participation in the Nursing School Rachel Haddock Lobo and in
      the Brazilian Association of Nursing (ABEn). The study is based on the concepts
      of symbolic power, habitus and symbolic struggle of Pierre Bourdieu. The primary
      sources are documents which were collected in the Documentation Center of Escola
      de Enfermagem Ana Neri (EEAN--Ana Neri School of Nursing) in the Federeal
      University of Rio de Janeiro (UFRJ) and at the Memory Center of the Faculty of
      Nursing (FENF) in the State University of Rio de Janeiro (UERJ). The data was
      collected between August 2000 and April 2001 by means of document analysis
      script. The outcomes showed that Zaira Cintra Vidal was born on 5 May 1903;
      graduated from the Nursing School of the National Public Health Department in
      1926; studied and post-graduated in the United States from 1927 until 1929 and
      returned to Brazil in 1943. Zaira Cintra Vidal was the founder of the Nursing
      School Rachel Haddock Lobo and was its first director for nine years. She also
      and took part in ABEn's Direction Board and in the Revista Anais de Enfermagem
      (Nursing Magazine).

PMID- 12240654
TI  - [The trajectory of the Brazilian Nurses Association-Alagoas].
AB  - This article outlines the trajectory of the Brazilian Association of Nursing
      (ABEn) in Alagoas and its influence in the organization of the nursing profession
      in this federal state. It points out that ABEn-AL was the first institution to
      organize nursing in Alagoas, since it was founded prior to any nursing graduation
      course or even any nursing syndicate. Therefore, ABEn is considered a decisive
      landmark in the political and professional organization of nursing in the state
      of Alagoas.

PMID- 12240655
TI  - [Nursing representation in the state of Goias].
AB  - The objective of this case study report is to stress the way nursing
      professionals in the federal state of Goias are represented. It was concluded the
      Brazilian Association of Nursing (ABEn) in Goias and other educational
      institutions, have promoted changes in the practices, attitudes and behavior of
      the nursing professionals through the incentive and investment on courses,
      seminars and other kind of events. The study also shows that the efforts to
      qualify the nursing profession have increased the participation of these workers
      in areas, which were not disputed by them before.

PMID- 12240656
TI  - [Trajectory and campaign of the Brazilian Nurses Association in Minas Gerais].
AB  - The present article describes the trajectory, the work and the achievements of
      the Brazilian Association of Nursing (ABEn) in Minas Gerais. It describes some
      contributions of the association for the growth and development of the nursing
      profession in Minas Gerais and in the whole country. The facts and events
      reported in this investigation were taken from meeting minutes, newspaper
      articles, journals of the association, records and summaries of events, and oral
      interviews. The study initially outlines the origin of the association in Brazil,
      establishing connections with the foundation and development of ABEn Minas
      Gerais. It also describes the most important events, struggles and achievements
      promoted by the twenty-two administrations of the association, which consolidated
      ABEn-Minas Gerais. The conclusion of the study is that the solidification of this
      branch was achieved due to the effort and involvement of people who really valued
      and wanted to develop the nursing profession.

PMID- 12240657
TI  - [Brazilian Nurses Association-Rio de Janeiro Chapter: a short history].
AB  - The objective of the present article is to reveal the work done by the Brazilian
      Association of Nursing (ABEn) in the federal state of Rio de Janeiro along its
      fifty-five years of history. It describes the foundation of the main office and
      regional branches, the acquisition of the building for the headquarters, the
      promotion of events, awards offered, achievements and other interesting facts
      that constitute the history of this association. The study also brings the names
      of the presidents and vice-presidents from 1963 until the present days. It
      finalizes with the event of the assassination of the president of the association
      and his wife, in 1999.

PMID- 12240658
TI  - From the Centers for Disease Control and Prevention. Barriers to children walking
      and biking to school--United States, 1999.

PMID- 12240659
TI  - From the Centers for Disease Control and Prevention. Unrecognized HIV infection,
      risk behaviors, and perceptions of risk among young black men who have sex with
      men--six US cities, 1994-1998.

PMID- 12240661
TI  - JAMA patient page. Birth labor.

PMID- 12240662
TI  - Cardiovascular and endocrine reactivity in older females: intertask consistency.
AB  - Age-related structural and functional changes in the cardiovascular,
      sympathoadrenomedullary (SAM), and hypothalamic-pituitary-adrenocortical (HPA)
      systems may affect the ability to reliably identify individual differences in
      response to stress. Heart rate, preejection period, respiratory sinus arrhythmia,
      respiratory rate, norepinephrine, epinephrine, adrenocorticotropic hormone, and
      cortisol were assessed in 64 healthy older women (mean = 67 years) in response to
      a mental arithmetic and public-speaking task. All cardiovascular and endocrine
      measures changed significantly during the tasks. All measures were consistent
      across the two tasks (r(s)s = .50 to .97). Moreover, a majority of women in this
      sample exhibited cross-task consistency in the relative activation of the
      autonomic, SAM, and HPA systems (i.e., response profiles). Further research is
      recommended to examine the significance of consistent individual differences in
      response profile.

PMID- 12240663
TI  - Effect of positive and negative emotion on stimulus-preceding negativity prior to
      feedback stimuli.
AB  - Stimulus-preceding negativity (SPN) was recorded to investigate the effect of
      positive and negative emotion on the SPN preceding feedback stimuli. In the time
      estimation task in which an acoustic stimulus was presented 3 s after a voluntary
      movement, (1) the negative valence (aversive band noise and pure tone) and (2)
      the positive valence (reward and no-reward) of feedback stimuli were manipulated.
      During noise conditions, participants received the band noise as a feedback
      stimulus except when their time estimations were accurate. They received a
      monetary reward for accurate time estimations under the reward conditions. The
      prefeedback SPN was larger under reward than no-reward conditions. In addition,
      the prefeedback SPN in the noise condition was larger compared with the pure tone
      condition. Our results appear to suggest that emotional anticipation is important
      in eliciting the prefeedback SPN.

PMID- 12240664
TI  - Comparison of hemodynamic responses to social and nonsocial stress: evaluation of
      an anger interview.
AB  - Hemodynamic responses to an anger interview and cognitive and physical stressors
      were compared, and the stability of associated hemodynamic reactions examined.
      Participants experienced control, handgrip, counting, and mental arithmetic tests
      and an anger interview on two occasions. Systolic and diastolic blood pressure,
      heart rate, stroke volume, and cardiac output were measured. Total peripheral
      resistance was also derived. The anger interview produced larger, more sustained
      changes in blood pressure in both sessions than the other stressors. These
      changes were largely a consequence of increased peripheral resistance. Consistent
      with previous findings, handgrip was associated with a resistance-type reaction
      whereas arithmetic was associated with a cardiac output-type reaction. There was
      low-to-modest stability of hemodynamic reactions to the interview. Further
      research is necessary to optimize its utility in studies of cardiovascular
      function. Nevertheless, the findings underscore the ability of ecologically
      relevant stressors to provoke unique configurations of cardiovascular activity.

PMID- 12240665
TI  - Hypoalgesic effect of caffeine in normotensive men and women.
AB  - Evidence from both hypertensive and normotensive individuals indicate that
      elevated blood pressure is associated with decreased pain sensitivity. The
      current study sought to experimentally raise blood pressure using 250 mg
      caffeine, and investigate its effects on the cold pressor pain experiences of 25
      men and 25 women. In a placebo-controlled repeated-measures experiment, caffeine
      increased systolic and diastolic blood pressure, as well as producing more
      clearheaded and energetic feelings. Caffeine produced higher pain threshold and
      pain tolerance levels compared to placebo, and women had a lower tolerance to
      pain than men. Finally, a significant association was found between caffeine
      related increase in systolic blood pressure and caffeine-related increase in pain
      tolerance. Furthermore, this association was the strongest in women. These
      results are discussed in light of future directions for pain and hypertension
      research.

PMID- 12240666
TI  - Selective attention and response inhibition alter phase-dependent cardiac
      slowing.
AB  - This study examined the effects of visual selective attention and stimulus
      discriminability on phasic heart rate changes. Grating stimuli consisting of four
      vertical bars were presented left or right from fixation. Participants attended
      to one side of the screen and responded with a button press to attended target
      stimuli that were defined by shorter middle bars. Stimulus discriminability was
      manipulated by increasing the length of the middle bars of targets. To examine
      the time course of response inhibition, participants had to respond to auditory
      probe stimuli that were presented occasionally and unpredictably at varying
      intervals following the visual stimulus. Responses to targets and probes
      following attended nontargets were slower in the difficult condition. Heart rate
      slowed in anticipation of a target and accelerated back to baseline afterwards.
      Phase-dependent cardiac slowing was larger for attended nontargets compared to
      unattended nontargets and was more pronounced in the difficult condition. These
      findings were interpreted vis-a-vis inhibition accounts of phase-dependent
      cardiac slowing.

PMID- 12240667
TI  - Cross-modal warning effects on reflexive and voluntary reactions.
AB  - Previous research has shown that warning signals can speed the onset of the
      startle-blink reflex. To relate this phenomenon to warning effects on voluntary
      reaction time (RT), the latencies of both reflexive and voluntary responses were
      measured for nine factorial combinations of warning and reflexogenic stimulus
      modalities. Previous failures to use factorial manipulations of warning (S1) and
      reaction (S2) stimulus modalities have led to conflicting results in both the
      reflex and RT literatures. Using psychophysically matched warning signals, we
      found a facilitation of reflex latency that was nonspecific with regard to S1 and
      S2 modality. Furthermore, there was no support for the widely held assumption
      that visual stimuli are inherently less alerting than auditory and cutaneous
      stimuli. A between-group comparison showed that simultaneous voluntary reactions
      do not distort the reflex facilitation effect. These results support the validity
      of reflex facilitation as a simple model system for studying warning effects on
      sensorimotor reactions.

PMID- 12240668
TI  - Voluntary facial expression and hemispheric asymmetry over the frontal cortex.
AB  - Brain activity was monitored while 36 participants produced facial configurations
      denoting anger, disgust, fear, joy, and sadness. EEG alpha power was analyzed
      during each facial pose, with facial conditions grouped according to the
      approach/withdrawal motivational model of emotion. This model suggests that
      "approach" emotions are associated with relatively greater left frontal brain
      activity whereas "withdrawal" emotions are associated with relatively greater
      right frontal brain activity. In the context of a bilateral decrease in
      activation, facial poses of emotions in the withdrawal condition resulted in
      relatively less left frontal activation in the lateral-frontal, midfrontal and
      frontal-temporal-central region, but not in the parietal region, as predicted.
      Findings in the approach condition were less consistently supportive of
      predictions of the approach/withdrawal model. Implications for the
      approach/withdrawal model and for the emotion eliciting potential of voluntary
      facial movement are discussed.

PMID- 12240669
TI  - Neural substrates for visual perceptual grouping in humans.
AB  - Two experiments investigated the neural mechanisms of Gestalt grouping by
      recording high-density event-related brain potentials (ERPs) during
      discrimination tasks. In Experiment 1, stimulus arrays contained luminance
      defined local elements that were either evenly spaced or grouped into columns or
      rows based on either proximity or similarity of shape. Proximity grouping was
      indexed by a short-latency positivity (110-120 ms) over the medial occipital
      cortex and a subsequent right occipitoparietal negativity. Grouping by similarity
      was reflected only in a long-latency occipitotemporal negativity. In Experiment
      2, proximity grouping was examined when local elements were defined by motion
      cues, and was again associated with a medial occipital positivity. However, the
      subsequent long-latency negativity was now enhanced over the left posterior
      areas. The implications of these results to the neural substrates subserving
      different grouping processes are discussed.

PMID- 12240670
TI  - Differential conditioning to facial emotional expressions: effects of hemispheric
      asymmetries and CS identification.
AB  - Previous studies on aversive learning have suggested a right hemispheric
      advantage for eliciting autonomic reactions to a masked conditioned facial
      stimulus (CS) depicting anger. The present study investigated the effects of
      visual field (VF), stimulus awareness, and emotional valence of the CSs on
      indicators of conditioning (bilateral SCRs, HR) using a differential conditioning
      paradigm (N = 41). In Group 1, four different negatively valenced facial
      expressions (CS+) but not four positively valenced CS- were associated with an
      unconditioned stimulus (US, aversive vocalization, 97 dB, 3 s) during
      acquisition. Group 2 received a treatment reversal with positive CS+ associated
      with the US. In a repeated measures design, CSs were presented with or without
      awareness during extinction (two weeks interval, order counterbalanced). SOAs
      were adapted for each subject and condition prior to the experiment so that
      identification performance was approaching chance level. The results revealed
      that both negative and positive facial expressions could be aversively
      conditioned providing evidence for a generalization of learning in the valence
      dimension. During extinction, preattentive negative CS+ presented to the left VF
      showed a trend towards greater electrodermal and cardiac reactions. However, no
      such effect emerged under full awareness of the CSs. These results confirm and
      further specify the nature of hemispheric asymmetries in emotional associative
      learning.

PMID- 12240671
TI  - Piecewise latent growth curve modeling of systolic blood pressure reactivity and
      recovery from the cold pressor test.
AB  - Latent growth curve methodology was used to model systolic blood pressure
      reactivity and recovery from the cold pressor test. A piecewise regression
      approach permitted the separate but simultaneous modeling of the two components
      (reactivity and recovery) of the stress process. Data came from a study of 99
      participants classified on the basis of gender, ethnicity, and family history of
      hypertension. Their systolic blood pressure was assessed at rest, during the cold
      pressor test, and during a task recovery period. A measure of task appraisal and
      readings from ambulatory blood pressure monitoring during a workday were also
      examined. The article illustrates a step-by-step approach to modeling reactivity
      and recovery. Results indicated that both reactivity and recovery were associated
      with subsequent systolic blood pressure at work.

PMID- 12240672
TI  - Hyperventilation beyond fight/flight: respiratory responses during emotional
      imagery.
AB  - Hyperventilation (HV) is often considered part of a defense response, implying an
      unpleasant emotion (negative valence) combined with a strong action tendency
      (high arousal). In this study, we investigated the importance of arousal and
      valence as triggers for HV responses. Forty women imagined eight different
      scripts varying along the arousal and valence dimensions. The scripts depicted
      relaxation, fear, depressive, action, and desire situations. After each trial,
      the imagery was rated for valence, arousal, and vividness. FetCO2, inspiratory
      and expiratory time, tidal volume, and pulse rate were measured in a nonintrusive
      way. FetCO2 drops and decreases in inspiratory and expiratory time occurred in
      all but the depressive and the relaxation scripts, suggesting that a defense
      conceptualization of hyperventilation is not always appropriate.

PMID- 12240673
TI  - The detection of constancy amidst change in children: a dissociation of
      preattentive and intentional processing.
AB  - This study examined whether 7-9-year-old children preattentively build memories
      of constancy for individual stimulus features, and if these representations are
      affected by variability of other stimulus features. This was achieved by looking
      at the mismatch negativity (MMN) event-related potential to a duration deviant
      occurring in a stimulus environment in which one or two other features constantly
      changed. Performance data were also collected, to look at the correspondence
      between the effects of this manipulation on preattentive and intentional deviance
      detection. MMN data indicated that the children built a preattentive feature
      based memory of constancy that was not affected by the number of varying
      features. In contrast, intentional deviance detection was considerably impaired
      by the introduction of feature variability. This dissociation is at variance with
      previous studies that usually report close association between MMN and behavior.

PMID- 12240674
TI  - Effects of rapid versus slow accumulation of eight hours of sleep loss.
AB  - The present study assessed alertness, memory, and performance following three
      schedules of approximately 8 hr of sleep loss (slow, intermediate, and rapid
      accumulation) in comparison to an 8-hr time in bed (TIB) sleep schedule. Twelve
      healthy individuals aged 21-35 completed each of four conditions according to a
      Latin Square design: no sleep loss (8-hr TIB for 4 nights; 2300-0700), slow (6-hr
      TIB for 4 nights; 0100-0700), intermediate (4-hr TIB for 2 nights; 0300-0700),
      and rapid (0-hr TIB for 1 night) sleep loss. On each day, participants completed
      a multiple sleep latency test (MSLT), a probed-recall memory task, a psychomotor
      vigilance task, a divided attention task, and the Profile of Mood States. "Rapid"
      sleep loss produced significantly more impairment on tests of alertness, memory,
      and performance compared to the "slow" accumulation of a comparable amount of
      sleep loss. The impairing effects of sleep loss vary as a function of rate,
      suggesting the presence of a compensatory adaptive mechanism operating in
      conjunction with the accumulation of a sleep debt.

PMID- 12240675
TI  - Breast-feeding and maternal cardiovascular function.
AB  - Two studies examined the effects of breast-feeding on maternal cardiovascular
      function. In the first experiment, groups of breast-feeding and bottle-feeding
      women were compared on preejection period (PEP), heart rate (HR), cardiac output
      (CO), and total peripheral resistance (TPR) recorded for 1-min periods before and
      during standard laboratory stressors. Compared with bottle-feeders, breast
      feeders had higher CO throughout the session, and greater decreases in CO and
      increases in TPR during cold pressor. In the second experiment, HR and blood
      pressure (BP) were compared before and after one breast-feeding and one bottle
      feeding session in a within-subjects design. Both feeding methods increased BP
      but decreased HR, and systolic BP was higher for the breast-feeding than the
      bottle-feeding condition. Both studies support the notion that breast-feeding
      alters maternal cardiovascular function, possibly through the actions of
      oxytocin.

PMID- 12240676
TI  - The n-back as a dual-task: P300 morphology under divided attention.
AB  - The n-back task was hypothesized to be a dual task, permitting the imposition of
      parametrically increasing attentional and working memory demands, while keeping
      constant the demands of an embedded matching subtask. Visual targets were
      presented for 200 ms every 2.2 s at pseudorandomly varying positions on a
      computer screen. Participants were required to remember the most recent 0, 1, 2,
      or 3 positions and responded with a choice button push to whether the current
      target position matched the position presented n items previously. P300 peak
      latency was constant across n-back tasks, reflecting constant perceptual and
      cognitive demands of the matching subtask. P300 peak amplitude decreased with
      increasing memory load, reflecting reallocation of attention and processing
      capacity away from the matching subtask to working memory activity. These data
      support a dual-task nature of the n-back, which should be considered when
      employing this paradigm.

PMID- 12240677
TI  - Homology and the optimization of DNA sequence data.
AB  - Three methods of nucleotide character analysis are discussed. Their implications
      for molecular sequence homology and phylogenetic analysis are compared. The
      criterion of inter-data set congruence, both character based and topological, are
      applied to two data sets to elucidate and potentially discriminate among these
      parsimony-based ideas.

PMID- 12240678
TI  - Exploring the behavior of POY, a program for direct optimization of molecular
      data.
AB  - The performance of the computer program for phylogenetic analysis, POY, and its
      two implemented methods, "optimization alignment" and "fixed-states
      optimization," are explored for four data sets. Four gap costs are analyzed for
      every partition; some of the partitions (the 18S rRNA) are treated as a single
      fragment or in increasing fragments of 3, 10, and 30. Comparisons within and
      among methods are undertaken according to gap cost, number of fragments in which
      the sequences are divided, tree length, character congruence, topological
      congruence, primary homology statements, and computation time.

PMID- 12240680
TI  - History of the American Institute of Pharmacy.

PMID- 12240679
TI  - Efficiency of parallel direct optimization.
AB  - Tremendous progress has been made at the level of sequential computation in
      phylogenetics. However, little attention has been paid to parallel computation.
      Parallel computing is particularly suited to phylogenetics because of the many
      ways large computational problems can be broken into parts that can be analyzed
      concurrently. In this paper, we investigate the scaling factors and efficiency of
      random addition and tree refinement strategies using the direct optimization
      software, POY, on a small (10 slave processors) and a large (256 slave
      processors) cluster of networked PCs running LINUX. These algorithms were tested
      on several data sets composed of DNA and morphology ranging from 40 to 500 taxa.
      Various algorithms in POY show fundamentally different properties within and
      between clusters. All algorithms are efficient on the small cluster for the 40
      taxon data set. On the large cluster, multibuilding exhibits excellent parallel
      efficiency, whereas parallel building is inefficient. These results are
      independent of data set size. Branch swapping in parallel shows excellent speed
      up for 16 slave processors on the large cluster. However, there is no appreciable
      speed-up for branch swapping with the further addition of slave processors (>16).
      This result is independent of data set size. Ratcheting in parallel is efficient
      with the addition of up to 32 processors in the large cluster. This result is
      independent of data set size.

PMID- 12240681
TI  - Poisoning the spindle: serendipity and discovery of the anti-tumor properties of
      the Vinca alkaloids.

PMID- 12240682
TI  - Sources of drug market data [1953].
AB  - The major sources of market and economic information on the pharmaceutical
      industry have been discussed. An annotated bibliography, including all sources
      mentioned in this discussion and a number of supplementary sources, follows.

PMID- 12240683
TI  - Witnesses of the body: medico-legal cases in seventeenth-century Rome.
AB  - Studying early modern medico-legal testimonies can enrich our understanding of
      witnessing, the focus of much research in the history of science. Expert
      testimonies were well established in the Roman Cannon law, but the sphere of
      competence of expert witnesses - one of the grounds on which seventeenth-century
      physicians claimed social and intellectual authority- troubled contemporary
      jurists. By reconstructing these debates in Counter Reformation Rome, and by
      placing in them the testimonies given by Poalo Zacchia, one of the founding
      fathers of legal medicine, this article discusses the epistemological and social
      issues surrounding the definition of expertise about the body in court. It shows
      how a high-ranking expert witness would define his competence versus the legal
      authority on the one hand, lower-status expert witnesses on the other. But it
      also explores the interactions between specific legal constraints, for example
      about eye witnessing, and the ways in which different kinds of witnesses would
      use the body as a source of evidence for testimony. While engaging with medico
      legal issues including the ambiguous signs of childbirth and the (in)visibility
      of pain, the article examines their meanings within Counter Reformation social
      controversies, including control over sexuality, imposition of discipline and the
      social status of physicians.

PMID- 12240684
TI  - Testimony in seventeenth-century English natural philosophy: legal origins and
      early development.
AB  - This essay argues that techniques for assessing testimonial credibility were well
      established in English legal contexts before they appeared in English natural
      philosophy. 'Matters of fact' supported by testimony referred to human actions
      and events before the concept was applied to natural phenomena. The article
      surveys English legal views about testimony and argues that the criteria for
      credible testimony in both legal and scientific venues were not limited to those
      of gentle status. Natural philosophers became concerned with testimony when they
      shifted their attention from universal statements about nature to particular
      natural and experimental histories constructed by English naturalists. The shift
      to a more Baconian approach to natural investigation, itself shaped in part by
      legal concepts and practice, made it possible for members of the Royal Society to
      adopt an already familiar and societally approved approach to testimony. However,
      the essay also suggests how the use of scientific instruments and the desire to
      avoid the adversarial processes of the law modified legal conditions for fact
      determination, and made it possible for later generations to associate the
      concept of fact, supported by credible testimony, with the natural rather than
      the human sciences.

PMID- 12240685
TI  - Testing testimony: toxicology and the law of evidence in early nineteenth-century
      England.
AB  - This essay's principle objective is to examine how, when confronted with a case
      of possible criminal poisoning, early nineteenth-century English toxicologists
      sought to generate and to represent their evidence in the courtroom. Its
      contention is that in both these activities toxicologists were inextricably
      engaged in a complex communicative exercise. On the one hand, they distanced
      themselves from the instabilities of language, styling themselves as testifiers
      to fact alone. But at the same time, they saw themselves as deeply implicated in
      the difficulties of forging a coherent signifying system out of a disparate
      collection of signs that in themselves bore no intrinsic meaning. The analysis
      has three main components: first, two suggest why criminal poisoning featured so
      prominently in the burgeoning legal literature on evidence which provided the
      framework for expert testimony in English courts; next, to show that the
      scientific evidence offered by toxicologists in poisoning cases can be usefully
      understood as a form of (unstable) language; and finally, to suggest that this
      recourse to signs informed the toxicologist's encounter with another type of
      courtroom expert-the legal advocate-who was equally (though differently)
      interested in manipulating signs in order to construct (and deconstruct) legally
      sanctioned proof.

PMID- 12240686
TI  - High bone density due to a mutation in LDL-receptor-related protein 5.

PMID- 12240687
TI  - Major radiation exposure.

PMID- 12240688
TI  - Major radiation exposure.

PMID- 12240690
TI  - Major radiation exposure.

PMID- 12240689
TI  - Major radiation exposure.

PMID- 12240691
TI  - Diabetic nephropathy.

PMID- 12240692
TI  - Aspirin for the primary prevention of coronary events.

PMID- 12240693
TI  - Pleasure: the common currency.
AB  - At present as physiologists studying various homeostatic behaviors, such as
      thermoregulatory behavior and food and fluid intake, we have no common currency
      that allows us to equate the strength of the motivational drive that accompanies
      each regulatory need, in terms of how an animal or a person will choose to
      satisfy his needs when there is a conflict between two or more of them. Yet the
      behaving organism must rank his priorities and needs a common currency to achieve
      the ranking (McFarland & Sibly, 1975, Phil. Trans. R. Soc. Lond. 270 Biol 265
      293). A theory is proposed here according to which pleasure is this common
      currency. The perception of pleasure, as measured operationally and
      quantitatively by choice behavior (in the case of animals), or by the rating of
      the intensity of pleasure or displeasure (in the case of humans) can serve as
      such a common currency. The tradeoffs between various motivations would thus be
      accomplished by simple maximization of pleasure. In what follows, the scientific
      work arising recently on this subject, with be reviewed briefly and our recent
      experimental findings will be presented. This will serve as the support for the
      theoretical position formulated in this essay.

PMID- 12240694
TI  - Our bodies, ourselves and the women's health movement.

PMID- 12240695
TI  - A medical poem by Dr. Oliver Wendell Holmes (Boston, 1838).